PMID- 11315290
TI  - Juvenile papillomatosis of the breast in a 9-year-old girl.
AB  - Juvenile papillomatosis (JP) is a rare benign, proliferative breast tumor in
      children. We observed a 9-year-old girl with a large soft-tissue mass at the
      lower outer quadrant of the left breast. Ultrasonography showed an ill-defined,
      inhomogeneous mass with numerous small, hypoechoic areas. The tumor was
      completely excised. Histopathology revealed JP of the breast. The case is
      presented and the literature is reviewed.

PMID- 11315291
TI  - Biliary atresia with hyperandrogenic amenorrhea.
AB  - The etiology of hyperandrogenic amenorrhea in a patient with biliary atresia
      successfully treated by a Kasai operation was unclear. Delayed puberty and
      menarche were evident at 16 years of age. Investigations showed no luteinizing
      hormone (LH)-follicle-stimulating hormone surge. A LH-releasing hormone
      provocative test showed a normal response. Peripheral aromatization of androgens
      appeared to function normally. Free testosterone (T) was normal, however, plasma
      levels of sex-hormone-binding globulin and total T were high. After menarche at
      18 years of age, anovulatory menstrual cycles continued. A combination of
      estrogen and progesterone therapy was effective. A possible explanation may be
      that metabolic clearance of T is reduced in the presence of liver cirrhosis and a
      portosystemic shunt.

PMID- 11315292
TI  - Surgical emphysema--an unusual finding in spontaneous neonatal gastric
      perforation.
AB  - A neonate presented with extensive surgical emphysema of the abdominal wall and a
      spontaneous gastric perforation. This clinical presentation is very rare. Early
      diagnosis and treatment improve the clinical outcome.

PMID- 11315293
TI  - Cecal perforation presenting as abdominal-wall necrotizing fasciitis.
AB  - The preoperative diagnosis of a cecal perforation associated with Salmonella
      infection as a cause of abdominal-wall necrotizing fasciitis (AWNF) is clinically
      difficult. Computed tomography of the abdomen is helpful, and can detect the
      combined presence of a pneumoscrotum and pneumoperitoneum. Its presence indicates
      a patent processus vaginalis, which acts as the primary route for the spread of
      the intra-abdominal infectious process into the abdominal wall. An exploratory
      laparotomy should be done to confirm the presence of intra-abdominal pathology in
      order to avoid delayed treatment.

PMID- 11315294
TI  - Omphalocele, colonic atresia, and Hirschsprung's disease: an unusual cluster of
      malformations in a single patient.
AB  - Omphalocele, colonic atresia (CA), and Hirschsprung's disease (HD) are
      individually rare congenital malformations. An association between CA and HD has
      been described, but the co-occurrence of all three malformations has not been
      previously reported. We present an infant born with all three malformations and
      review the management issues relevant to this case, with an emphasis on the
      importance of considering co-existent HD in any infant born with CA.

PMID- 11315295
TI  - Cystic rectal duplication: a rare cause of neonatal bladder-outlet obstruction
      and hydronephrosis.
AB  - A case of cystic rectal duplication (RD) is presented. A 7-day-old female was
      admitted with acute urinary retention, voiding difficulty, and abdominal
      distention since she was 4 days of age. Ultrasound and abdominal computed
      tomography (CT) demonstrated a huge, cystic mass in the pelvis and abdomen that
      resulted in acute urinary retention and bilateral hydronephrosis. CT-guided
      drainage of the lesion followed by transabdominal surgical excision resulted in a
      cure. Pathologic examination demonstrated a RD lined by respiratory epithelium.

PMID- 11315296
TI  - Pseudoexstrophy of the bladder: a rare variant.
AB  - A 15-day-old female presented with a healed omphalocele and a triangular
      musculoskeletal defect in the hypogastric area similar to the defect seen in
      classic bladder exstrophy. The bladder was normal on exploration. The defect was
      successfully closed using a bilateral anterior pubic ramotomy. Only ten cases of
      pseudoexstrophy have been reported in the world literature.

PMID- 11315297
TI  - Complete vaginal prolapse: an unusual presentation of anovestibular fistula.
AB  - An adolescent girl with an anovestibular fistula presenting as a complete vaginal
      prolapse and large-bowel obstruction is reported. The prolapse was reduced
      manually after repeated bowel washouts and a divided high sigmoid colostomy. The
      patient is awaiting posterior sagittal anorectoplasty. Possible etiopathologic
      factors of the prolapse are discussed. A vaginal prolapse in a patient with an
      anorectal malformation has not been reported previously in the English
      literature.

PMID- 11315298
TI  - Unilateral ovarian agenesis and fallopian tube maldescent.
AB  - Unilateral ovarian agenesis (UOA) and fallopian descent problems are very rare
      congenital defects. We present an unusual case of UOA associated with fallopian
      tube maldescent discovered incidentally during a laparotomy in a female infant
      for a persistent heterogeneous right ovarian cyst refractory to needle
      aspiration. A necrotic, hemorrhagic paratubal cyst was found associated with a
      normal right adnexa. The left ovary was absent and a rudimentary left fallopian
      tube was found tightly stretched over the sigmoid colon to the left
      retroperitoneum. This previously unreported constellation of anomalies may carry
      significant potential risks for bowel obstruction and later fertility.

PMID- 11315299
TI  - Complete spontaneous regression of a functioning adrenocortical carcinoma in an
      infant.
AB  - A 9-month-old female presented with Cushing's syndrome. Investigations suggested
      the diagnosis and revealed a functioning left adrenal carcinoma without
      metastasis. However, when the abdomen was explored 30 days later after
      controlling the hypertension only normal adrenals were encountered, suggesting
      complete spontaneous regression. This is the fourth case of its kind. The case
      along with a review of this rare phenomenon is presented.

PMID- 11315300
TI  - Techniques available for the management of massive sacrococcygeal teratomas.
AB  - An infant born in the 34th week of gestation weighing 5,355 g with a massive
      sacrococcygeal (SC) tumor was delivered by elective cesarean section. An
      ultrasonographic examination showed solid and cystic components in the tumor.
      Resection was successfully undertaken with insertion of a Nelaton catheter into
      the rectum to avoid unnecessary impairment of the viscera. The tumor weighed
      2,380 g, measured 25 x 14 x 11 cm, and was clinicopathologically diagnosed to be
      a SC teratoma. This experience and other publications show that several
      considerations including control of hemorrhage and coagulopathies, visceral
      protection, and avoidance of wound infection are necessary to facilitate the
      surgical management of massive SC tumors. Several suggestions are made concerning
      the pre- and intraoperative management of this rare tumor.

PMID- 11315301
TI  - Life-threatening mediastinal teratoma in a neonate.
AB  - This report describes a newborn with a large mediastinal teratoma (MT) presenting
      with severe respiratory distress (RD) at birth. At operation, there was no space
      for dissection because the huge cystic and solid tumor completely occupied the
      left hemithorax. After evacuation of the cystic component, the tumor was removed
      successfully. To our knowledge, only 16 newborn infants with MT presenting with
      RD have been reported. Operative morbidities occurred in one-half of the cases.
      We have reviewed the literature to discuss the potential risks of this entity.

PMID- 11315302
TI  - Congenital pseudarthrosis of the ulna and radius in two cases of
      neurofibromatosis type 1.
AB  - Two children with neurofibromatosis type 1 who presented at birth with congenital
      pseudarthrosis of the ulna and radius are described. The patients were treated
      with broad resections. As a consequence, the forearms were reduced in length. The
      osteotomies were stabilized in one patient first with endomedullary nailing and
      then with a free vascularized fibular graft. In the second patient the osteotomy
      was stabilized by external fixation. Using these techniques, rapid and excellent
      healing and normal function were achieved. In contrast to the lower extremity,
      reduction of the length of the forearm can be accepted to a certain extent. If
      necessary, an extension osteotomy can be performed at a later date.

PMID- 11315303
TI  - Staged reduction of gastroschisis: a simple method.
AB  - Staged reduction of abdominal contents using a silastic sheet has become standard
      management in gastroschisis where primary closure is not possible. With the
      introduction of a pre-made Silastic silo coupled to a spring-loaded ring (Ben
      Tec, Sacramento, CA), the procedure can be done at the bedside. We present a
      simple technique utilizing a disposable umbilical-cord clamp that makes reduction
      a fast, one-physician procedure and present a preoperative step that facilitates
      tension-free closure of the abdominal fascia.

PMID- 11315304
TI  - "Cuff-stitch" to prevent inadvertent dislodgement of central venous catheters.
AB  - The insertion of central venous catheters (CVCs) is an established practice in
      the management of children who need long-term total parenteral nutrition or
      chemotherapy. Inadvertent falling out of CVCs before the cuff becomes
      incorporated in the tissues is a commonly encountered problem. The technique
      described involves inserting a circular stitch in the subcutaneous plane before
      the catheter is placed. Once the CVC is pulled into position, the "cuff-stitch"
      lays around the catheter distal to the cuff, narrows the tunnel, and prevents
      accidental dislodgement.

PMID- 11315305
TI  - Ode to the Lubbock Longfellowette! [Pediatr Surg Int (1999) 15: 598].

PMID- 11315306
TI  - Rare complication of intestinal volvulus with perforation of the small bowel
      secondary to the peritoneal end of the ventriculoperitoneal shunt (VPS).

PMID- 11315307
TI  - Hydatid cyst within a cystic adenomatoid malformation: first case report.

PMID- 11315308
TI  - Paravertebral neoplasm in a child with Down syndrome (DS).

PMID- 11315309
TI  - Bronchoscopic removal of tracheobroncheal foreign bodies: value of patient
      history and timing.
AB  - Between 1990 and 1999, 741 bronchoscopic procedures were performed in 698
      children, 594 of whom were evaluated for foreign-body aspiration (FBA) (mean age
      3.9 years, male:female 287/307). Based on the presenting symptoms, clinical
      outcome, and complications, two major groups were identified. Group 1 consisted
      of 438 patients with a definitive history of FBA. Most were admitted soon after
      the aspiration with sudden onset of symptoms such as coughing, choking, wheezing,
      and respiratory distress. Group 2 comprised 156 patients with chronic pulmonary
      infections and/or atelectasis without a definitive history of FBA. The most
      common radiographic finding was emphysema of one lung in group 1 (61.1%) and
      pneumonia in group 2 (70%). Among the patients in whom a FB was removed, the
      percentage of normal radiography was 17%. The FB was identified and removed in
      83% of cases in group 1. The complication rate in this group was 9.8%, and all
      the complications were treated medically. Only 2 patients required intercostal
      drainage. In group 2, a FB was identified in 25% of bronchoscopic examinations
      and 17% of the patients developed complications. One of these patients underwent
      an urgent thoracotomy due to bilateral tension pneumothoraces and 2 required
      tracheostomies. Patients with a definitive history of FBA, even with a normal
      physical examination and radiographic findings, must undergo bronchoscopic
      investigation. Cases with late presentation and chronic pulmonary infection are
      at high risk. In this group care should be take in determining the indication and
      timing of bronchoscopy in order to prevent life-threatening complications.

PMID- 11315310
TI  - Congenital lobar emphysema: experience with 21 cases.
AB  - A retrospective study of all cases (n = 21) of congenital lobar emphysema (CLE)
      treated at the Royal Hospital, Muscat, from September 1988 to August 1999 was
      performed. The presentation, diagnosis, treatment, and outcome are reviewed. All
      21 patients were nonwhite. Thirteen had left-upper-lobe, 7 right-middle-lobe, and
      1 right-upper-lobe involvement. Of the 14 upperlobe cases, 10 had severe symptoms
      whereas only 2 of the 7 middle-lobe cases had severe symptoms. Mildly symptomatic
      cases on conservative treatment invariably needed surgery if infected. It is
      concluded that CLE is not limited to white infants, upper-lobe disease is more
      severe than middle-lobe disease, and nonoperative measures are likely to be
      useful in mildly symptomatic cases involving the middle lobe.

PMID- 11315311
TI  - Respiratory status of infants with esophageal atresia.
AB  - In infants with esophageal atresia (EA), lung opacities on a chest radiograph
      (CXR) are usually considered the cause of respiratory distress (RD). However, in
      some instances signs of RD and CXR changes show no correlation. The aim of this
      study was to investigate the pathogenesis of RD in EA patients with a normal CXR.
      In 41 infants with EA, CXR findings were correlated with clinical manifestations
      and blood-gas analysis data. The degree of abnormal gas exchange was quantitated
      by the arterial/alveolar oxygen tension ratio (a-ARO2). Of the 41 infants,
      39(95%) presented with RD. No lung opacities were found in 130 of 294 CXRs
      examined (44%). An a-ARO2 below 0.75 (lower limit of normal) was calculated in
      215 of 247 arterial blood samples analyzed (87%). When a temporal correlation was
      established, RD with a clear CXR was characterized by signs of extra- and
      intrathoracic airway obstruction, often associated with an a-ARO2 below 0.75. The
      degree of hypoxemia was greater than the degree of hypercapnia. We conclude that
      in infants with EA, RD with a clear CXR is related to both tracheomalacia and
      upper-airway obstruction that may cause miliary atelectasis not detected by
      conventional CXR with intrapulmonary shunting and hypoxemia.

PMID- 11315312
TI  - Investigation of the intra-abdominal oesophagus and hiatus in fetal rats with
      oesophageal atresia and tracheo-oesophageal fistula.
AB  - After surgical management of their oesophageal atresia (OA) and tracheo
      oesophageal fistula (TOF), most patients exhibit evidence of gastro-oesophageal
      reflux (GOR) and many have oesophagitis. However, the aetiology of the GOR is
      still controversial. This study was undertaken to document whether there are
      congenital abnormalities in the intra-abdominal oesophagus and the hiatus in the
      fetal rat with OA and TOF following exposure to adriamycin (ADR). Time-pregnant
      rats were injected daily with either saline or 2 mg/kg ADR intraperitoneally on
      gestational days (GD) 6-9. The fetuses (n = 56) from 8 litters were harvested on
      GD 21 for examination. The length of the oesophagus between the diaphragmatic
      crura and the gastro-oesophageal junction (GOJ) and the sizes of the stomach and
      the oesophageal hiatus were measured under a dissecting microscope. The length of
      the oesophagus between the diaphragmatic crura and the GOJ in the ADR-treated
      fetuses (0.85 +/- 0.37 mm) was significantly shorter than in control fetuses
      (2.41 +/- 0.32 mm) (P < 0.0001). The size of the stomach in ADR-treated fetuses
      (5.30 +/- 1.01 mm) was significantly smaller than in the controls (8.07 +/- 0.49
      mm) (P < 0.001). Moreover, the size of the oesophageal hiatus in ADR-treated
      fetuses (1.16 +/- 0.43 mm) was markedly larger than in the controls (0.32 +/- 0.1
      mm) (P < 0.0001). These results showed that the congenital abnormalities in ADR
      treated rat fetuses may account for the oesophageal functional disorders seen
      after surgical correction in patients who have OA and TOF.

PMID- 11315313
TI  - Mathematical modeling of the onset of capillary formation initiating
      angiogenesis.
AB  - It is well accepted that neo-vascular formation can be divided into three main
      stages (which may be overlapping): (1) changes within the existing vessel, (2)
      formation of a new channel, (3) maturation of the new vessel. In this paper we
      present a new approach to angiogenesis, based on the theory of reinforced random
      walks, coupled with a Michaelis-Menten type mechanism which views the endothelial
      cell receptors as the catalyst for transforming angiogenic factor into
      proteolytic enzyme in order to model the first stage. In this model, a single
      layer of endothelial cells is separated by a vascular wall from an extracellular
      tissue matrix. A coupled system of ordinary and partial differential equations is
      derived which, in the presence of an angiogenic agent, predicts the aggregation
      of the endothelial cells and the collapse of the vascular lamina, opening a
      passage into the extracellular matrix. We refer to this as the onset of vascular
      sprouting. Some biological evidence for the correctness of our model is indicated
      by the formation of teats in utero. Further evidence for the correctness of the
      model is given by its prediction that endothelial cells will line the nascent
      capillary at the onset of capillary angiogenesis.

PMID- 11315314
TI  - Chaos and population disappearances in simple ecological models.
AB  - A class of truncated unimodal discrete-time single species models for which low
      or high densities result in extinction in the following generation are
      considered. A classification of the dynamics of these maps into five types is
      proven: (i) extinction in finite time for all initial densities, (ii)
      semistability in which all orbits tend toward the origin or a semistable fixed
      point, (iii) bistability for which the origin and an interval bounded away from
      the origin are attracting, (iv) chaotic semistability in which there is an
      interval of chaotic dynamics whose compliment lies in the origin's basin of
      attraction and (v) essential extinction in which almost every (but not every)
      initial population density leads to extinction in finite time. Applying these
      results to the Logistic, Ricker and generalized Beverton-Holt maps with constant
      harvesting rates, two birfurcations are shown to lead to sudden population
      disappearances: a saddle node bifurcation corresponding to a transition from
      bistability to extinction and a chaotic blue sky catastrophe corresponding to a
      transition from bistability to essential extinction.

PMID- 11315315
TI  - A dynamical model for plant cell wall architecture formation.
AB  - We discuss a dynamical mathematical model to explain cell wall architecture in
      plant cells. The highly regular textures observed in cell walls reflect the
      spatial organisation of the cellulose microfibrils (CMFs), the most important
      structural component of cell walls. Based on a geometrical theory proposed
      earlier [A. M. C. Emons, Plant, Cell and Environment 17, 3-14 (1994)], the
      present model describes the space-time evolution of the density of the so-called
      rosettes, the CMF synthesizing complexes. The motion of these rosettes in the
      plasma membrane is assumed to be governed by an optimal packing constraint on the
      CMFs plus adherent matrix material, that couples the direction of motion, and
      hence the orientation of the CMF being deposited, to the local density of
      rosettes. The rosettes are created inside the cell in the endoplasmatic reticulum
      and reach the cell-membrane via vesicles derived from Golgi-bodies. After being
      inserted into the plasma membrane they are assumed to be operative for a fixed,
      finite lifetime. The plasma membrane domains within which rosettes are activated
      are themselves also supposed to be mobile. We propose a feedback mechanism that
      precludes the density of rosettes to rise beyond a maximum dictated by the
      geometry of the cell. The above ingredients lead to a quasi-linear first order
      PDE for the rosette-density. Using the method of characteristics this equation
      can be cast into a set of first order ODEs, one of which is retarded. We discuss
      the analytic solutions of the model that give rise to helicoidal, crossed
      polylamellate, helical, axial and random textures, since all cell walls are
      composed of (or combinations of) these textures.

PMID- 11315316
TI  - ATP-sensitive K+ transport in adrenal chromaffin granules.
AB  - In the present study the influx of 86Rb+, a K+ analogue, was studied in
      mitochondria, microsomes and chromaffin granules prepared from adrenal gland
      medulla. The most active electrogenic 86Rb+ transport was found in the membrane
      fraction identified as chromaffin granules by marker enzyme estimation. The
      transport was found to be sensitive to ATP, ATP gamma S, ADP and to the triazine
      dyes, but not to AMP and cAMP. The inhibition induced by ATP was observed in the
      absence of externally added Mg2+, suggesting that a free nucleotide, rather than
      the ATP-Mg complex, was required for inhibition. Furthermore, the 86Rb+ influx
      was found to be inhibited by Mg2+ alone, but not by Ca2+ and antidiabetic
      sulfonylureas. The 86Rb+ influx was not stimulated by potassium channel openers.
      In conclusion, our results indicate that an electrogenic, ATP-sensitive potassium
      transport system operates in the chromaffin granule membrane.

PMID- 11315317
TI  - Apoptosis in relation to neuronal loss in experimental Creutzfeldt-Jakob disease
      in mice.
AB  - Apoptosis constitutes a genetically determined process to eliminate superfluous
      or damaged cells in tissues. Deficiencies in apoptosis regulation are involved in
      different pathologies including prion diseases. Some experimental studies show
      that neuronal loss--one of the hallmarks of prion diseases may be accomplished by
      apoptosis. We evaluated twenty five mice infected experimentally with the
      Fujisaki strains of CJD and sacrified sequentially in one week intervals.
      Apoptotic cells in various brain regions were detected by in situ end labelling
      (TUNEL) and electron microscopy in comparison with neuronal cell loss. The number
      of labelled cells per brain was very low--from a few labelled cells 6 weeks after
      inoculation to a maximum of 14 in the terminal stage. The number of neurones
      counted in 8 selected areas were considerably lower in terminally sick animals
      (20 and 21 week of incubation period) than in control mice. The mean value of
      loss of neuronal cells was 32%. The greatest loss (55%) of neurones was noted in
      the septal nuclei of the paraterminal body and the least lost (16%) in the
      hypothalamus. Compared to the extensive neuronal loss (30-50%), the number of
      apoptotic cells detected by in situ end labelling seems to be very low, and the
      process of neuronal death become more intensive during the progression of the
      disease.

PMID- 11315318
TI  - Lipid metabolism parameters in patients with Alzheimer's disease and their first
      degree relatives.
AB  - Recently, it was suggested that the presence of total cholesterol (TC), age and
      sex interaction in Alzheimer's type dementia (AD) is linked with the
      apolipoprotein E (APOE) genotype. Our objective was to determine whether the
      serum lipid profile in AD patients and their first degree non-demented relatives
      of a certain age (NDR) was dependent on APOE genotype. We included 28 mild to
      moderate AD and 30 NDR according to DSM-III-R and NINCDS-ADRDA criteria. NDR
      individuals were investigated in an age group similar to the AD group (brother
      sister relationship) and in a group including younger individuals (AD patients
      children relationship). Our data indicate significant differences between
      decreased total cholesterol and low density lipoprotein cholesterol ratio in the
      group of AD patients versus NDR individuals of similar age, independent of APOE
      genotype, and an increased total cholesterol and low density lipoprotein
      cholesterol ratio in a group of AD patients versus their children of the same
      genotype. There was no significant correlation between triglycerides and high
      density lipoprotein levels with APOE genotype in any of the tested groups. In
      conclusion, there was a decreased selected lipid serum profile parameters in AD
      compared to age matched non demented first degree relatives.

PMID- 11315319
TI  - In vitro pituitary prolactin, growth hormone and follicle stimulating hormone
      secretion during sexual maturation of female rats primed with melatonin.
AB  - The influence of in vivo melatonin administration on in vitro pituitary follicle
      stimulating hormone (FSH), growth hormone (GH) and prolactin secretion, as well
      as the possible influence of dopamine (DA) were evaluated in prepubertal (31-day
      old), pubertal (33-day-old) and adult female rats at diestrus phase of the sexual
      cycle. The in vitro pituitary hormone secretions were evaluated at basal rate for
      the first hour of incubation only, in Krebs Ringer phosphate (KRP) (I1) and after
      a second hour of incubation with KRP (I2) or with KRP+DA (I2 plus DA). I1PRL
      secretion was significantly higher in 33-day-old control and melatonin treated
      (MEL) rats as compared to I2 periods. However, in 31-day-old rats I1 secretion
      was higher than in the I2 or I2+DA periods, in MEL rats. In vitro GH secretion
      was significantly higher at I1 than during I2 periods in the control 31- and 33
      day-old groups, but not in MEL rats. The only significant effect of DA was the
      elevation of GH in prepubertal MEL rats. In vitro FSH release was increased by
      melatonin in 31- and 33-day-old female rats. No differences in PRL, GH and FSH
      secretion were found in adult rats. In conclusion, the results show that
      melatonin effects upon in vitro pituitary gland activity are reproductive-stage
      dependent modifying the secretory capacity of the lactotrop, gonadotrop and
      somatotrop during prepubertal and pubertal ages but not in adult rats studied at
      a quiescent phase of the sexual cycle.

PMID- 11315320
TI  - Microglial and astroglial cells in the rat paraclaustral reservoir during
      postnatal development: an immunohistochemical study.
AB  - A immunohistochemical study of postnatal development of the paraclaustral
      reservoir of migrating cells in the rat brain was performed using anti-GFAP (for
      astroglia), ED1 and OX-42 (for microglia) antibodies. From birth to the 4th day
      of postnatal life most GFAP-positive cells in the paraclaustral reservoir are
      similar to transitional astroglia. From the end of the first postnatal week they
      have the morphology of mature astrocytes, although during the next week, their
      density was a slightly higher than in neighboring structures. On the 21st day,
      the morphology and density of astroglial cells in the ventral part of the
      external capsule did not differ from the surrounding regions. ED1/OX-42- positive
      microglial cells present in the paraclaustral reservoir during the first
      postnatal week represented ameboid microglia; their density was clearly higher
      than in the neighboring structures. During the second week they began to
      transform into ramified microglia and from the 21st day on, only OX-42 positive
      resting microglial cells were observed in the ventral part of the external
      capsule. We suggest that the paraclaustral reservoir is a place of accumulation
      of astroglia and microglia during brain development and may possibly serve as
      source of glial cells for neighboring structures. Alternatively, these glial
      populations may perform local developmental functions.

PMID- 11315321
TI  - Interrelations between nuclear-factor kappa B activation, glial response and
      neuronal apoptosis in gerbil hippocampus after ischemia.
AB  - Spatial and temporal relations between transcriptional factor NF kappa B
      activation and glia reaction in gerbil hippocampus after transient cerebral
      ischemia has been studied. Activation of protein binding to NF kappa B consensus
      oligonucleotide was determined by electrophoretic mobility gel shift assay (EMSA)
      in homogenates from dorsal (DP- an equivalent of CA1 sector) and abdominal (AbP-
      containing CA2-4 and gyrus dentatus) parts of hippocampus. A significant
      activation of NF kappa B binding was observed exclusively in DP as early as 3 h
      after ischemia and at this time that response preceded any other morphological
      signs of postischemic tissue injury. This early enhancement of NF kappa B binding
      was followed by microglia activation visualized in CA1 pyramidal region at 24 h
      of recovery by histochemical staining with lectin from Ricinus communis (RCA
      120). Simultaneously, only a moderate increase of immunostaining against glial
      fibrillary acidic protein (GFAP) was observed homogeneously in all parts of
      hippocampus. This uniform pattern of astrogliosis was preserved until
      postischemic day 3-4, when apoptotic DNA fragmentation in CA1 pyramidal neurons
      had been clearly documented by TUNEL staining. At this period however, continuous
      elevation of NF kappa B binding in DP corresponded with similar response
      manifested also in AbP of the hippocampus. These results evidence a preferential
      NF kappa B involvement in an early microglia activation in the apoptogenic CA1
      sector, although its role in a later astrocytic response to ischemia could not be
      neglected too.

PMID- 11315322
TI  - Heart rate changes in partially restrained rats during behaviorally and
      pharmacologically evoked emotional states.
AB  - The effect of fear and relief from fear on heart rate (HR) was studied in
      partially restrained adult male rats. The emotional state was influenced
      behaviorally with the use of Pavlovian aversive conditioning procedure, and
      pharmacologically by injections of the selected anxiolytics and anxiogenics. A
      signal of danger (DS)--light or tone, preceded tail-shock (excitatory trials),
      while a signal of safety (SS), respectively tone or light, overlapped last 3s of
      5s DS and predicted an omission of this expected aversive event (inhibitory
      trials). To assess the stability of HR changes to DS and SS we analyzed whether
      and how the experimental conditions (modality and position of signals, the ratio
      of numbers of excitatory to inhibitory trials in the session) influenced HR. HR
      changes to DS were different in pattern, stability and direction when compared to
      HR changes in response to SS. Reactions to DS, although accompanied mainly by
      conditioned bradycardia, were not consistent and depended on experimental
      conditions. However, the SS always evoked conditioned tachycardia. Anxiolitycs-
      benzodiazepines (diazepam and midazolam) and buspirone--influenced HR in
      nonconsistent manner. Anxiogenics--PTZ and FG7142 were without significant
      effects on HR. HR could not be trusted therefore as direct index of
      pharmacologically induced emotional states. The results are discussed in the
      context of possible biobehavioral meaning of HR changes in response to danger and
      safety and their reliability as fear/relief correlates.

PMID- 11315323
TI  - Sulfurtransferase activity and sulfur compound content in Rana temporaria brain
      following hibernation.
AB  - The activity of rhodanese, 3-mercaptopyruvate sulfurtransferase and gamma
      cystathionase and the content of glutathione and sulfane sulfur compounds were
      determined in Rana temporaria brain in April. The high sulfane sulfur level
      observed in the spring seems to be associated with protection against cellular
      oxidative stress after the period of hibernation with its minimal oxidative
      metabolism.

PMID- 11315324
TI  - Mice can learn roughness discrimination with vibrissae in a jump stand apparatus.
AB  - An adaptation of roughness discrimination task successfully used on rats was
      performed on mice. It was found that mice can master discrimination of rough
      surfaces using only mystacial vibrissae. This task can be used for studying
      sensory abilities of genetically modified mice as well as dynamics and
      pharmacology of complex sensory learning.

PMID- 11315325
TI  - [Xanthogranulomatous pyelonephritis. Our experience and review of the
      literature].
AB  - BACKGROUND: Ten cases of xanthogranulomatous pyelonephritis (XGP) with diagnostic
      and therapeutic observation are described and other experiences reported in the
      literature are analyzed. METHODS: The clinical, laboratory and radiological
      features of 10 patients who had undergone nephrectomy in our Istitute, between
      October 1993 and March 2000, with a postoperative pathological diagnosis of XGP
      have been retrospectively re-evaluated. RESULTS: The most frequent symptom was
      flank pain. All the patients presented leucocytosis. Urine culture was positive
      for Proteus Mirabilis in four patients (40%) and for E. Coli in three (30%). In
      all the patients an ultrasound scan and urography were performed, six patients
      (60%) had undergone a CT scan and two of them (20%) a MRI. In six patients (60%)
      urinary lithiasis was associated and it was ramified in four of them (40%). The
      disease was always unilateral, affecting the right kidney in six cases and the
      left one in the other four. In three cases (30%) it presented in the focal form.
      The treatment was always surgical and it consisted of nephrectomy; a conservative
      surgical approach was used in two cases (20%). At the follow-up 4 patients (40%)
      showed recurrent urinary tract infections. None presented relapse. CONCLUSIONS:
      XGP is an uncommon chronic inflammatory disease, often associated with urinary
      tract infections and/or urolithiasis. The clinical presentation is nonspecific so
      that differential diagnosis with other kidney diseases becomes difficult. A CT
      scan can be helpful in formulating diagnosis. The treatment is surgical and it
      consists of a nephrectomy, while a conservative approach can be reserved in some
      cases for the focal form. Cases treated with antibotics have been described.

PMID- 11315326
TI  - [Nephron-sparing treatment of kidney neoplasms in transplanted kidney. Our
      experience].
AB  - BACKGROUND: To evaluate survival rate, follow-up and renal function in patients
      treated with "nephron-sparing" approach due to cancer in a transplanted kidney.
      METHODS: During the 18 years' activity of our Transplantation Centre 3 renal
      carcinomas in transplanted kidneys (0.24%) have been found. Diagnoses were made
      in one case during transplantation procedures and, in the remaining two, 1 month
      and 10 years after. All tumours were unifocal, small (10, 12 and 18 mm of
      diameter), capsulated and low stage (T1). The resection of the mass ("nephron
      sparing" surgery) and of a layer (1 cm thick) of the tissue surrounding the
      tumour was performed. The histological exam showed in all cases low grade (G2)
      renal cell carcinoma and negative surgical margins. RESULTS: 138, 94 and 15
      months after transplant all patients are alive, without disease recurrence and
      with good renal function. In all cases the doses of immune-suppressive therapy
      were reduced. CONCLUSIONS: Renal cancer in transplanted kidneys is generally
      treated with nephrectomy. On the contrary, we decided to apply the same criteria
      which are accepted for the treatment of renal neoplasms in general and then to
      perform a "nephron-sparing" surgery when the tumour is small, capsulated and with
      negative surgical margins at the intraoperative histological exam. In personal
      experience good results from the oncologic and nephrologic point of view have
      been accomplished.

PMID- 11315327
TI  - [Uretero-intestinal anastomosis using the ureteral nipple technique with personal
      modification in continent urinary diversion].
AB  - BACKGROUND: This report presents the follow-up data for the incidence of stenosis
      and reflux in 143 split cuff nipple ureteral intestinal anastomoses in continent
      urinary diversions. METHODS: 74 ureteral implants (1990-1995) were performed
      using the original technique, whereas a technical modification was adopted after
      1996. This was used in 69 implants and consisted of the removal of a button of
      bowel tract in order to obtain a linear implant to the reservoir, instead of
      using a simple enterotomy at the level of the anastomosis. RESULTS: The rate of
      clinically significant refluxes was 2.2%, whereas the incidence of stenosis fell
      from 6.8% in the group using the original technique to 2.9% in those using the
      modified technique. CONCLUSIONS: Anastomosis using the split cuff ureteral nipple
      technique is simple to perform and is indicated in peristaltic and non-dilatated
      ureters. Moreover, this technical modification improves the overall results.

PMID- 11315328
TI  - [Epididymal anomalies in cryptorchism and in persistent peritoneo-vaginal duct].
AB  - BACKGROUND: Various percentage incidences (36-75%) of the duct system morphologic
      alterations in cryptorchidism syndrome have been reported in the literature.
      Etiopathogenic factors, responsible for this syndrome, are yet to be specified,
      as is their correlation with testicular descent in the scrotum and peritoneal
      vaginal duct regression. METHODS: In a prospective multicentric study we have
      documented seminal duct anatomy in 566 children, undergoing inguinal or scrotal
      surgical exploration due to acute scrotal syndrome (group A, "control group"),
      cryptorchidism (group B), and peritoneal-vaginal duct patency syndromes (group
      C), for a total of 726 testicles. On the basis of anatomical configurations,
      explored testicles have been subdivided into three groups: normal testicles (type
      I), suspension anomalies (type II), obstruction anomalies (type III). Prevalence
      of the above anatomical configurations in the various groups has been
      statistically evaluated by the chi 2 test. RESULTS: Results have highlighted a
      significant prevalence (p < or = 0.01) of severe duct system obstructive
      anomalies (type III) in children with cryptorchidism (group B) and in children
      with vaginal duct patency (group C). These results can justify the hypothesis of
      a close correlation between testicle embryologic migration process in the scrotal
      sac and seminal duct development; this latter seems furthermore correlated with
      peritoneal duct regression. CONCLUSIONS: The drawn conclusion is that duct system
      morphologic alterations in cryptorchidism, due to their seriousness and
      incidence, can condition final fertility capability.

PMID- 11315329
TI  - Use of small calibre JJ ureteral stent with anti-reflux valve in uretero-vesical
      anastomosis during renal transplantation.
AB  - BACKGROUND: We report our experience in transplantation proceedings with the use
      of small caliber JJ ureteral stent with antireflux valve during uretero-vesical
      anastomosis. METHODS: During renal transplantations we usually perform an uretero
      cystoneostomy with antireflux technique according to Lich Gregoir. In the past we
      used to intubate the uretero-vesical anastomosis only in particular cases; since
      April 1998 we performed 112 single and 8 double transplants and in all cases we
      positioned a 12 cm long paediatric 4.8 Ch JJ ureteral stent with antireflux
      valve, in order to reduce urologic complications. The vesical catheter was
      usually removed in 6o-7o day and the ureteral stent 40-60 days after
      transplantation. RESULTS: We have performed 129 uretero-vesical anastomoses and
      we complained only one case of early dehiscence of the anastomosis (unilateral in
      a double transplant) and two cases of late stents' displacement. We noticed no
      stenosis of the anastomosis and no dysfunction in urine outflow from the upper
      urinary ways. CONCLUSIONS: The routinary use of paediatric JJ ureteral stents
      with antireflux valve was decisive in drastically reducing early urologic
      complications after renal transplantation. Furthermore, the risk of vesico
      ureteral reflux is almost completely reduced, thanks to the technique adopted for
      the anastomosis which allows a physiologic-like antireflux mechanism, to the
      presence of the antireflux valve and to the early recovery of the physiologic
      ureteral peristalsis, which is promoted by the small calibre of the stent. These
      factors lead to a faster recovery of the renal function, with excellent results
      from the nephrologic and urologic points of view.

PMID- 11315330
TI  - [Role of nitric oxide in the urogenital system: physiology and pathology].
AB  - A review has been made on the role of nitric oxide in the physiology and
      pathophysiology of penis, bladder, prostate and the nervous structures involved
      in the urinary control. NO is an essential mediator in penile erection and his
      action can be modulated by sildenafil. Nitric oxide could be involved in bladder
      detrusor relaxation and in the development of interstitial cystitis. Little is
      known about the role of nitric oxide in the physiology and pathophysiology of the
      prostate: this molecule is released by the epithelial and stromal cells of the
      prostate, and by the prostatic nerves. Actually some studies hypothesize a role
      played by nitric oxide in benign prostatic hyperplasia development.

PMID- 11315331
TI  - [Rational approach to the patient with urination disorders caused by cervico
      urethral obstruction].
AB  - Benign prostatic hypertrophy is the most frequent cause of cervico-urethral
      obstruction in adults. The symptomatology is complex and varied, and includes
      both irritative and obstructive symptoms. A number of methods are used to
      evaluate-quantify obstruction caused by benign prostatic hypertrophy. A series of
      tests are traditionally used to identify disorders caused by altered vesical
      filling (LUTS) and the degree of obstruction (BOO). An analysis of the various
      methods generally allows the most suitable treatment to be commenced. This
      critical review aimed to identify the real value and specificity of each method
      in relation to the possibility of quantifying the degree of cervico-urethral
      obstruction.

PMID- 11315332
TI  - [Large calcifications on double J ureteral endoprosthesis "forgotten" in situ.
      Report of a clinical case].
AB  - Ureteral endoprostheses can be complicated by incrustations, sometimes making it
      impossible to withdraw the stent. A case in which the use of cistolithotripsy and
      of extracorporeal shock-wave lithotripsy (ESWL) allowed withdrawal of a double J
      ureteral stent with large incrustations is reported. The stent was placed 3 years
      before. Epidemiology, aetiology and therapeutic aspects of encrusted ureteral
      stents are discussed.

PMID- 11315333
TI  - [Repeated bladder metastases from renal cell carcinoma. Report of a case with
      particular attention to the use of immunomodulators].
AB  - The case of repeated metastases of the bladder from renal cell carcinoma in a 59
      year old male patient is presented. Two years after nephrectomy the ureteral
      stump and the bladder were interested by two different metastases. Afterwards,
      other nine metastases developed into the bladder during the following 12 months.
      Biopsy with coagulation were performed in any case. Bladder metastases ranged
      between 2 and 4 mm. No other metastasis was discovered by MRI and skeletal
      scintigraphy. Thirteen months after the first bladder metastasis, intracavitary
      Bacillus Calmette-Guerin was used. No report was found in the literature about
      BCG in the treatment of superficial bladder metastases from renal cell carcinoma.
      However 15 months from beginning of BCG treatment no metastasis developed from
      the bladder that now is disease-free after a follow-up of 19 months.

PMID- 11315334
TI  - From the intestinal neobladder to the bioartificial bladder: remarks on some
      biological implications.
AB  - In an attempt to avoid the complications associated with use of bowel for bladder
      augmentation or replacement (systemic metabolic imbalances, malignancy, etc.),
      various solutions have been proposed for an artificial orthotopic neobladder:
      total alloplastic prosthetic bladder in nonbiological material (silicon rubber,
      polyurethane, etc.); tissue-engineered bladder by the patient's own urothelial-
      and smooth muscle--cells obtained by biopsy of a urinary segment with less
      neoplastic potential and cultured in vitro, then seeded onto biodegradable
      bladder-shaped scaffold, autografted in the original host; bladder augmentation
      or replacement using acellular matrix derived from small-intestinal submucosa or
      from bladder or ureter as a scaffold structure for the subsequent regrowth of
      functional organ. Tissue-engineering technology with autologous native cells is
      being undertaken for every type of organ within the urinary tract. At the present
      moment, other roads are less practicable, e.g. to obtain "spare bladders" from
      human therapeutic cloning or from transgenic-humanized animals.

PMID- 11315335
TI  - Synthesis of the beta-D-glucuronides of 2,3-, 3,4-, and 2,6-dichlorophenol.
AB  - The beta-D-glucuronides of 2,3-, 3,4-, and 2,6-dichlorophenol (1-3) were prepared
      by a modified Koenigs-Knorr synthesis. As the alkaline hydrolysis of
      perpivaloylated methyl (2,3-dichlorophenyl)-glucuronate 1a led to a dehydrated
      glucuronide, the preparation of peracetylated methyl dichlorophenylglucuronates
      with subsequent cleavage of the ester bindings under mild conditions was
      preferred.

PMID- 11315336
TI  - Synthesis and cyclooxygenase inhibitory properties of novel (+) 2-(6-methoxy-2
      naphthyl)propanoic acid (naproxene) derivatives.
AB  - Halomethylation of naproxene (1) occurs regioselectively in position 5 and
      subsequently--in situ or on treatment with silver nitrate--leads to naproxene
      "dimers" with two naproxene units, 5,5'-connected through a ethenylene (3) and a
      methylene (4) bridge, respectively. Two of the new naproxene derivatives were
      screened for their cyclooxygenase inhibitory properties relative to naproxene.
      Both 5-chloromethyl naproxene (2) and 2-(5-((carboxyethyl)-2-methyloxynaphthyl)-6
      methoxy-2-naphthyl)propanoic acid (4) were inactive in the concentration range of
      0.1-10 mumole against both COX-1 and COX-2, indicating that bulky substituents in
      position 5 in naproxene are unfavourable for both COX-1 and COX-2 inhibition.

PMID- 11315337
TI  - Reactions of 5-amino-3-methylisoxazole-4-carboxylic acid hydrazide with carbonyl
      compounds: immunological activity and QSAR studies of products.
AB  - A series of 4-imino derivatives of the 5-amino-3-methylisoxazole-4-carboxylic
      acid hydrazide and 5-amino-3-methylisoxazole[5,4-d]-6,7-dihydropyrimidine has
      been prepared by condensation of 5-amino-3-methylisoxazole-4-carboxylic acid
      hydrazide with carbonyl compounds. The resulting products were evaluated for
      their immunological activities in the models of the humoral and cellular immune
      responses of mice in vivo and concanavalin A (Con A) and lipopolysaccharide (LPS)
      induced splenocyte proliferation. In addition, effects on polyclonal antibody
      production by human peripheral blood cells in culture were investigated. For all
      studied compounds we carried out quantum chemical calculations at ab initio B3LYP
      6-31G(d, p) level. The stimulatory or inhibitory effects depended strongly on the
      origin and location of substitunets, which is described in the conclusions and
      was supported by QSAR studies.

PMID- 11315338
TI  - Synthesis and muscarinic activity of 1,2,3,4-tetrahydropyrimidine derivatives.
AB  - 3-Methyl-1,2,3,4-tetrahydropyrimidine-5-carbaldehyde O-substituted oximes 4 and 1
      (3-methyl-1,2,3,4-tetrahydropyrimidin-5-yl)ethanone O-substituted oximes 9 have
      been prepared as bioisosteric congeners of arecoline which is a muscarinic
      agonist for treatment of Alzheimer's disease. Starting from pyrimidine-5
      carbaldehyde 1, formation of the 3-methylpyrimidinium salt and subsequent
      reduction afforded 1,2,3,4-tetrahydropyrimidine derivatives which were converted
      into oxalate salts in the interest of purity and stability. Binding affinities of
      prepared compounds for the cloned human muscarinic M1 receptor (h-M1) were
      determined by radioligand binding assay using [3H]-N-methylscopolamine (NMS).

PMID- 11315339
TI  - Cornified envelope formation by anthralin, simple analogues, and related
      anthracenones.
AB  - The ability of the antipsoriatic anthralin to induce HaCaT keratinocyte
      differentiation was investigated and correlated with its potency to inhibit
      proliferation of keratinocytes. To determine the structural requirements for this
      effect, anthralin and seventeen simple analogues or related anthracenones were
      examined for their ability to induce the formation of cornified envelope as a
      marker of terminal differentiation. Covalently cross-linked protein was measured
      as a key feature of this process. Induction of keratinocyte differentiation was
      significant at a concentration of 0.5 microM anthralin after 48 h exposure. The
      presence of the 1,8-dihydroxy groups is a critical determinant of cross-linking
      activity, since removing or exchanging these groups prevented the induction of
      keratinocyte differentiation. Furthermore, at least one hydrogen atom at the 10
      position of anthralin is required. Moreover, anthralin, anthralin dimer, and
      anthralin triacetate exhibited antiproliferative and antirespiratory activity at
      concentrations required to induce keratinocyte differentiation, suggesting a
      causality between these effects. In addition, cornified envelope formation was
      observed for a number of related anthracenones at concentrations as low as 1-5
      microM. In general, compounds containing benzoyl substituents, independent of the
      position in the anthralin nucleus, were more potent than those having benzyl
      substituents. Only marginal differences in cross-linking potency were observed
      within a number of phenylpropionyl substituted analogues, suggesting that the
      ability to induce keratinocyte differentiation is independent of the nature of
      substituents at the side chain.

PMID- 11315340
TI  - Synthesis, conformational studies, and investigations on the estrogen receptor
      binding of [R/S-1-(2,6-dichloro-4-hydroxyphenyl)ethylenediamine]platinum(II)
      complexes.
AB  - The syntheses, conformational studies, and investigations on the estrogen
      receptor binding of [R/S-1-(2,6-dichloro-4
      hydroxyphenyl)ethylenediamine]platinum(II) complexes (1-PtL2, 2L = leaving
      groups) are described. A Strecker synthesis using the 2,6-dichloro-4
      methoxybenzaldehyde, NaCN, and NH4Cl afforded the cyanoamine 1b, which was
      subsequently reduced with LiAlH4 to give the R/S-1-(2,6-dichloro-4
      methoxyphenyl)ethylenediamine 1a. Ether cleavage with BBr3 yielded R/S-1-(2,6
      dichloro-4-hydroxyphenyl)ethylenediamine 1 which was coordinated to platinum(II)
      by use of K2PtCl4 (1-PtCl2) and K2PtI4 (1-PtI2), respectively. Reaction of 1-PtI2
      with Ag2SO4 and coordination of tartronic acid led to the [R/S-1-(2,6-dichloro-4-
      hydroxyphenyl)ethylenediamine][hydroxymalonato]platinum(II) complex (1
      Pt(MalOH)). The spatial structure of 1 and its complexes was evaluated by
      spectroscopic and molecular modeling methods. In solution the complexes adopt a
      structure very similar to estradiol. However, the in vitro and in vivo tests for
      the compounds indicated neither affinity to the estrogen receptor nor estrogenic
      properties.

PMID- 11315341
TI  - Nonsteroidal anti-inflammatory drugs in systemic lupus erythematosus.
AB  - Up to 80% of patients with systemic lupus erythematosus (SLE) are treated with
      nonsteroidal anti-inflammatory drugs (NSAID) for musculoskeletal symptoms,
      serositis and headache. This survey reviews the literature on non-selective and
      selective inhibitors of cyclooxygenases with an emphasis on the efficacy and
      safety profile reported in SLE patients. No lupus-specific data on gastro
      intestinal side effects of NSAID exist. Both non-selective Cox-inhibitors and
      selective Cox-2 inhibitors induce renal side effects including sodium retention
      and reduction of the glomerular filtration rate. Lupus nephritis is a risk factor
      for NSAID-induced acute renal failure, but not for rare idiosyncratic toxic renal
      reactions to NSAID. In refractory nephrotic syndrome, NSAID have been used
      successfully. Cutaneous and allergic reactions to NSAID are increased in SLE
      patients as well as hepatotoxic effects, particularly with high dose aspirin.
      Whereas a variety of central nervous system side effects of NSAID are probably no
      more common in SLE patients than in others, aseptic meningitis has been reported
      more frequently. Ovulation and pregnancy can be adversely affected by Cox
      inhibitors. The antiplatelet effect of aspirin and non-selective Cox-inhibitors
      has a therapeutic potential in patients with the antiphospholipid syndrome (APS).
      In summary, treatment of SLE with NSAID requires awareness for the increased
      frequency of some side effects and close monitoring of toxicity.

PMID- 11315342
TI  - Treatment of lupus with corticosteroids.
AB  - Through direct signals to the nucleus mediated by the glucocorticoid receptor,
      exogenous glucocorticoids impact a broad array of cellular functions. DNA binding
      of the glucocorticoid receptor, depending upon the specific promoter to which the
      receptor binds, affects gene expression by recruiting transcription factors to
      the promoter or by interfering with the function of co-factors required for gene
      transcription. Steroid effects on the adhesion functions and release of products
      by phagocytic cells are prompt, occurring within hours of administration.
      Administration of corticosteroids results in rapid depletion of circulating T
      cells due to a combination of effects including enhanced circulatory emigration,
      induction of apoptosis, inhibition of T-cell growth factors, and impaired release
      of cells from lymphoid tissues. Corticosteroid effects on B-cell function and
      immunoglobulin production are more delayed. The broad, generally suppressive
      effects of corticosteroids on the immune response render them useful for the
      management of most organ system manifestations of lupus. Corticosteroid toxicity
      in lupus is notable for greater susceptibility to infections, osteoporosis,
      osteonecrosis and accelerated atherogenesis. Although use of corticosteroids for
      patients with severe disease manifestations is associated with higher numbers of
      deaths from infections, overall survival appears to be improved.

PMID- 11315343
TI  - Antimalarial therapy: a panacea for mild lupus?
AB  - Antimalarial therapy has a long and successful track record in the management of
      patients with mild SLE. Medium to long term use of hydroxychloroquine, alone or
      in combination with mepacrine, ameliorates lupus and may reduce the relapse rate.
      Recent guidelines for monitoring hydroxychloroquine have reduced the need for
      frequent visual checks. Antimalarials have other beneficial effects on lipid and
      glucose metabolism as well as having weak anticoagulant activity. They should be
      considered for most patients with mild lupus.

PMID- 11315344
TI  - Azathioprine therapy for patients with systemic lupus erythematosus.
AB  - Azathioprine is the only purine analog that is widely used for the management of
      systemic lupus erythematosus (SLE). For SLE patients without renal involvement,
      it is given to those patients who require a maintenance dose of 15 mg or higher
      of prednisone and for those who experience recurrent flares. Azathioprine in
      combination with steroids may be given to a large number of patients with lupus
      nephritis. It is also effective for patients with skin lesions, pneumonitis,
      thrombocytopenia or hemolytic anemia. Azathioprine may be used during pregnancy
      but not during lactation. It has not been shown to increase the risk for the
      development of malignancies among patients with SLE.

PMID- 11315345
TI  - Cyclophosphamide for the treatment of systemic lupus erythematosus.
AB  - Aggressive immunosuppressive therapy with cyclophosphamide has improved the
      outcome of major organ disease in lupus patients. Controlled trials have shown
      that pulse cyclophosphamide is the treatment of choice for patients with moderate
      to severe proliferative nephritis. Long-term follow-up of patients participating
      in these controlled trials suggests that combining pulse cyclophoshamide with
      pulse methylprednisolone increases efficacy but not toxicity. Retrospective case
      series have also shown that pulse cyclophosphamide therapy may be effective for
      the management of severe or refractory to standard therapy neuropsychiatric,
      pulmonary, cardiovascular and hematologic disease. Pulse cyclophosphamide is
      associated with an increased risk for herpes zoster infections in the short term
      and with sustained amenorrhea in the long-term. Recent studies have also drawn
      attention to the lack of response (or incomplete response) and flare of lupus
      after an initial response. In an effort to circumvent these limitations, current
      investigations explore the therapeutic potential of high-dose, immunoablative
      cyclophosphamide therapy or low-dose cyclophosphamide in combination with
      nucleoside analogs or biologic response modifiers.

PMID- 11315346
TI  - Methotrexate therapy in systemic lupus erythematosus.
AB  - There are 12 non-controlled and only two controlled studies using methotrexate
      (MTX) in a total of 207 SLE patients in the literature. The majority of these
      studies evaluated mainly cutaneous and/or articular involvement and attained good
      results. Two studies evaluated a small number of patients with lupus nephritis,
      achieving discordant results. Two other studies in pediatric onset systemic lupus
      erythematosus (SLE) also presented conflicting results, it being relevant that
      the one with poor response had the majority of patients with nephritis. One of
      the controlled trials was retrospective and concluded that MTX was effective in
      the treatment of antimalarial-resistant lupus arthritis and that toxicity leading
      to discontinuation of MTX was infrequent. The other controlled study was a double
      blind, randomized, placebo-controlled clinical trial that evaluated SLE patients
      with mild activity. The authors concluded that MTX was effective in controlling
      cutaneous and articular activity and permitted prednisone dose reduction. The
      side effects were frequent but only 10% of patients needed to discontinue the
      medication. The accumulative evidence suggests that MTX in a low weekly dose may
      be effective in SLE patients with articular and/or cutaneous involvement with no
      response to antimalarials and low-dose prednisone and in patients in whom we can
      not reduce prednisone dose due to articular or cutaneous activity. Caution is
      required concerning the side effects.

PMID- 11315347
TI  - The treatment of lupus with cyclosporin A.
AB  - Cyclosporin is a potent immunosuppressive drug and is frequently used in the
      therapy of autoimmune diseases, including systemic lupus erythematosus (SLE). Few
      large studies have been performed using this drug in SLE patients. However, small
      uncontrolled studies of patients with SLE have shown favourable results with a
      significant improvement in disease activity, a fall in anti ds DNA titres and
      proteinuria and an improvement in complement levels, leucopaenia and
      thrombocytopaenia. Interestingly, a consistent reduction in corticosteroid dosage
      often by as much as 50% is seen. Toxicity, especially with hypertension and renal
      impairment, occurs but usually reverses on dose reduction or the addition of an
      anti-hypertensive agent and is minimised by adherence to the strict monitoring
      guidelines. Large multi-centre randomised-controlled trials of the use of
      cyclosporin in SLE patients are underway and the results are eagerly awaited.

PMID- 11315348
TI  - Local therapy for cutaneous and systemic lupus erythematosus: practical and
      theoretical considerations.
AB  - Local therapeutic measures should be maximized in the management of lupus
      erythematosus (LE), particularly for patients with forms of LE-specific skin
      disease such as SCLE and CCLE. Local therapy consists of sun protection and
      locally-applied pharmacologic agents, e.g. topical/intralesional corticosteroids.
      Patients should be advised to avoid direct sun exposure, wear lightweight tightly
      woven clothing and broad-brimmed hats, and use broad-spectrum, water-resistant
      sunscreens. There are several modalities that enhance permeability of local
      therapeutics through the stratum corneum that could be applied to topical therapy
      of cutaneous LE, e.g. polar solvent, liposomal encapsulation, ethosomal system,
      iontophoresis, electroporation and sonophoresis. As novel and more effective
      modalities to deliver pharmacologic agents across the stratum corneum become
      available, therapeutics that have been experimental and untested thus far may
      become part of the local armamentarium in the near future. In addition,
      physical/contact therapy as well as dermatosurgical methods can be invaluable in
      enhancing self-image and quality of life of patients with disfiguring cutaneous
      LE lesions.

PMID- 11315349
TI  - Ultraviolet therapy in lupus.
AB  - This review examines the use of ultraviolet (UV) therapy in lupus erythematosus
      (LE), a disorder usually associated with abnormally increased photosensitivity.
      In addition to the abnormal cutaneous response to ultraviolet radiation (UVR)
      exposure, photo-aggravation of systemic disease activity in systemic LE (SLE) may
      also occur. However, courses of UVR exposure may also be used in the treatment or
      prophylaxis of various photodermatoses, and LE now appears to be included in that
      group. Thus, several studies have reported apparent benefits of phototherapy in
      both cutaneous and systemic LE, although the underlying mechanisms remain obscure
      and final confirmation of such efficacy is still awaited in continuing studies.

PMID- 11315350
TI  - Update on therapy--thalidomide in the treatment of lupus.
AB  - Thalidomide has been shown to be an effective treatment for cutaneous forms of
      lupus erythematous refractory to other therapies. Thalidomide has very serious
      side effects, including teratogenicity and neuropathy, which limit its clinical
      use in lupus to such severe refractory cases. Efficacy has been confirmed in
      several studies, although recurrence after discontinuation of treatment is
      frequent. More recent experience suggests that lower doses than originally used
      may be effective, which may result in a reduction in side effects. Much effort
      has been expended in studying the mechanisms of action of thalidomide, although
      as yet it is unclear which of the mechanisms identified to date contribute to its
      efficacy in treating cutaneous forms of lupus erythematosus. Identification of
      patients suitable for thalidomide therapy requires a rigorous selection process.
      Potential side effects should be clearly explained, particularly teratogenicity
      as many patients are young women. Written consent and a negative pregnancy test
      must be obtained prior to commencement of therapy. Reliable contraceptive
      measures should be strictly observed by patients taking thalidomide. Close
      clinical and neurophysiological supervision using nerve conduction studies should
      be undertaken.

PMID- 11315351
TI  - Apheresis for lupus erythematosus: state of the art.
AB  - PP is a safe, expensive, labor-intensive procedure. Its absolute SLE indications
      include hyperviscosity, cryoglobulinemia, pulmonary hemorrhage and TTP. PP may be
      useful in cyclophosphamide-resistant, serious, organ-threatening disease. It may
      be potentially useful in the antiphospholipid syndrome or mothers or children at
      risk for congenital heart block. Refinements in apheresis technology may expand
      the indications for PP.

PMID- 11315352
TI  - Treatment of systemic lupus erythematosus with bromocriptine.
AB  - Prolactin, a lactogenic hormone, is a cytokine and an important link between the
      immune and endocrine systems. Prolactin stimulated disease in autoimmune NZB/NZW
      mice. Treatment of the mice with the prolactin-lowering dopamine agonist,
      bromocriptine, suppressed anti-DNA and prolonged life spans. These findings have
      been applied to humans with systemic lupus erythematosus (SLE). An open-label
      study, a double blind study, and a study comparing bromocriptine to
      hydroxychloroquine provided evidence that bromocriptine therapy reduced flares
      and suppressed disease activity in SLE.

PMID- 11315353
TI  - Treatment of systemic lupus erythematosus with mycophenolate mofetil.
AB  - Mycophenolate mofetil is an immunosuppressive drug that is of established
      efficacy in renal transplantation. It inhibits the de novo pathway of purine
      synthesis and therefore lymphocyte proliferation. Mycophenylate mofetil has been
      shown to ameliorate the severity of renal injury in murine models of lupus
      nephritis. Recent studies suggest that it may also be effective in the treatment
      of patients with lupus nephritis when used in conjunction with steroids. These
      observations need to be confirmed in adequately sized randomised-controlled
      studies.

PMID- 11315354
TI  - High-dose intravenous immunoglobulins for lupus nephritis--a salvage
      immunomodulation.
AB  - Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease with a
      great diversity of clinical manifestations which is difficult to manage. IVIGs
      represent promising immunoregulatory agents with the ability to control SLE
      without subsequent predisposition to infectious complications. Despite the
      implied risk of developing renal failure due to IVIG, considerable beneficial
      effects on lupus nephritis are reported. In this review, the clinical and adverse
      effects, and mechanism of action, with special emphasis on modulation, of
      idiotypic network is discussed.

PMID- 11315355
TI  - Immunoablation and haemopoietic stem cell transplantation for severe autoimmune
      disease with special reference to systemic lupus erythematosus.
AB  - Internationally 397 patients (310 in Europe/Austalasia and 87 in North America)
      with severe autoimmune disease (AD) have received an autologous haemopoietic stem
      cell transplant (HSCT) following immunoablation, 32 with systemic lupus
      erythematosus (SLE). The 23 in the EBMT/EULAR database mostly received
      cyclophosphamide (Cy) and G-CSF as mobilisation followed by Cy and antithymocyte
      globulin (ATG) conditioning. Nineteen improved with five relapses (mostly mild to
      moderate) and there were three procedure-related mortalities. In the Chicago
      series, nine patients were entered, seven improved, one died following
      mobilisation and one from active disease 3 months after mobilisation. Randomised,
      prospective controlled phase III trials are desired, but by consensus, more phase
      I and II data is required to plan the optimal protocol.

PMID- 11315356
TI  - Monoclonal antibodies and other biologic therapies.
AB  - The treatment of systemic lupus erythematosus (SLE) presents a significant
      therapeutic challenge: multi-organ involvement and a variable disease course
      characterized by clinical exacerbations and remissions make it difficult to
      predict outcome. Few products have been specifically developed in this clinical
      indication and most accepted therapies have not been tested in randomized
      controlled trials in SLE. A variety of biologic agents under investigation as
      potential treatments for SLE are designed to interfere with specific immunologic
      responses, hopefully avoiding generalized immunosuppression. These include
      therapies to downregulate IL-10 and/or upregulate TGFb production. Agents which
      interfere with T cell activation and T cell-B cell collaboration, such as CTLA4
      Ig and anti-CD40 ligand monoclonal antibodies, may result in long term
      therapeutic benefit; alone or in combination, even following brief treatment
      courses. Products designed to decrease production of anti-dsDNA antibodies or
      inhibit complement activation may prevent immune complex deposition and
      amerliorate organ-specific manifestations such as renal disease. More aggressive
      interventions include gene therapy and stem cell transplantation. As these agents
      enter clinical trials, efforts to develop international consensus regarding trial
      methodology and outcome measures will be crucial to their successful development.

PMID- 11315357
TI  - Exogenous estrogen in systemic lupus erythematosus: oral contraceptives and
      hormone replacement therapy.
AB  - The role of exogenous estrogen in the initiation and maintenance of human SLE
      remains very controversial. Although cohort studies suggest an increase in the
      incidence of SLE with both oral contraceptives and hormone replacement therapy,
      recent retrospective studies suggest that the risk of flare is not increased with
      hormone replacement therapy. However, exogenous estrogen does increase
      hypercoagulability, an issue in SLE patients with antiphospholipid antibodies.
      The prospective SELENA study will ultimately address whether exogenous estrogen
      increases severe flares in SLE.

PMID- 11315358
TI  - Osteoporosis in systemic lupus erythematosus: prevention and treatment.
AB  - The patient with systemic lupus erythematosus (SLE) is at risk of osteoporosis
      through several factors: the inflammatory disease itself, disease-related co
      morbidity, and its treatment. Bone loss is apparent early in the disease and this
      may be confounded primarily by treatment with corticosteroids. Patients should be
      assessed for additional risk factors for osteoporosis and general lifestyle
      measures adopted. Bone mineral density measurement should be considered in SLE
      patients at high risk of osteoporosis, particularly those starting
      corticosteroids and in postmenopausal women. Calcium and vitamin D
      supplementation provide general prophylaxis and are a suitable first-line option.
      Hormone replacement should be used in hypogondal subjects unless contra
      indicated. In subjects at high fracture risk, particularly in postmenopausal
      women, bisphosphonate therapy should be considered as these agents have been
      shown to significantly reduce vertebral fracture risk. These measures should
      reduce the burden of osteoporosis and fracture in patients with lupus.

PMID- 11315359
TI  - Lipid-lowering drugs in lupus: an unexplored therapeutic intervention.
AB  - Lipid-lowering drugs have been shown to have profound actions beyond modulation
      of lipid profiles. Statins have been shown to reduce the levels of pro
      inflammatory cytokines and markers of acute phase response including C-reactive
      protein and serum amyloid A. Fibrates have also shown to reduce interleukin-6
      levels. Both groups of drugs seem to act through a peroxisomal proliferating
      activating receptor alpha mechanism to achieve these actions. In lupus, there is
      profound activation of cytokine production and the acute phase response and a
      markedly increased risk for the development of atherosclerosis. The role of lipid
      lowering drugs in the management of both the acute and chronic sequelae of lupus
      needs to be explored.

PMID- 11315360
TI  - Vaccination and systemic lupus erythematosus: the bidirectional dilemmas.
AB  - Vaccination has been perhaps the most important achievement in medicine of the
      last century. A hoard of infectious diseases that used to claim the lives of
      many, especially children, have been prevented and some even eradicated. However,
      it is possible that within this gift there is hidden a 'Trojan Horse'. During the
      last decade increasing numbers of reports regarding possible autoimmune side
      effects of vaccination, have been published. The existing data does not link the
      vaccines and the autoimmune phenomena observed in a causal relationship,
      nevertheless a temporal connection has been described. In this article we wish to
      address in particular the possible link between vaccines and systemic lupus
      erythematosus (SLE), namely two aspects of this inter-relationship: the
      occurrence of SLE following vaccination and outcome of immunization of known SLE
      patients.

PMID- 11315361
TI  - Antiaggregant and anticoagulant therapy in systemic lupus erythematosus and
      Hughes' syndrome.
AB  - Antiaggregant and anticoagulant drugs are essential in the management of the
      manifestations due to antiphospholipid syndrome (APS) in patients with primary
      Hughes' syndrome or systemic lupus erythematosus. Coumadin derivatives (warfarin
      and acenocumarol), heparin and aspirin are used for secondary thromboprophylaxis
      and treatment of recurrent miscarriage. The available evidence for each
      indication is reviewed in this paper. There is still debate regarding the optimal
      intensity of oral anticoagulation, the best drug combination for pregnancy
      failure in APS and the management of asymptomatic patients with antiphospholipid
      antibodies.

PMID- 11315362
TI  - Diet and lupus.
AB  - The effect of dietary modifications has been extensively studied in lupus animal
      models. Calorie, protein, and especially fat restriction, caused a significant
      reduction in immune-complex deposition in the kidney, reduced proteinuria and
      prolongation of the mice's life span. The addition of polyunsaturated fatty acids
      (PUFAs), such as fish oil or linseed oil, was also related to decreased mice
      morbidity and mortality in animal models of lupus and of antiphospholipid
      syndrome. PUFAs such as eicosapetaenoic acid (EPA) and docosahexaenoic acid (DHA)
      competitively inhibit arachidonic acid with a resultant decrease in inflammatory
      eicosanoids and cytokines. Human studies support the effect of a PUFAs-enriched
      diet, both scrologically and clinically. Large scale clinical studies are needed
      to confirm the primary results.

PMID- 11315363
TI  - Gifts from industry--look the gift horse in the mouth!

PMID- 11315364
TI  - Medicare reimbursement--the new math?

PMID- 11315365
TI  - Medical couples: the most stressed (and surprised) segment of married people.

PMID- 11315366
TI  - When an attorney calls, find out why before you start talking.

PMID- 11315367
TI  - At the statehouse: funnel deadlines near, bills are beginning to move.

PMID- 11315368
TI  - Treating TMD patients.

PMID- 11315369
TI  - Using live patients.

PMID- 11315370
TI  - Implant placement.

PMID- 11315371
TI  - Carpal tunnel syndrome.

PMID- 11315372
TI  - Secondhand smoke may increase periodontal disease risk.

PMID- 11315373
TI  - Do you ever discuss dietary or nutritional matters with your patients?

PMID- 11315374
TI  - Hidden herbal therapies.

PMID- 11315375
TI  - Celecoxib and rofecoxib. The role of COX-2 inhibitors in dental practice.
AB  - BACKGROUND: In recent years, dental practitioners have relied on ibuprofen and
      other nonsteroidal anti-inflammatory drugs, or NSAIDs--such as naproxen,
      diflunisal and ketoprofen--to manage acute and chronic orofacial pain. Two NSAIDs
      that recently came on the market, celecoxib and rofecoxib, have been developed to
      limit the adverse effects seen after chronic use of NSAIDs. LITERATURE REVIEWED:
      The authors have summarized all available publications describing the human
      pharmacokinetics, clinical pharmacology and known adverse effects of these new
      specific cyclooxygenase-2, or COX-2, inhibitors. CONCLUSIONS: Although
      peripherally acting analgesics are remarkably effective, chronic administration
      of nonselective COX inhibitors has been associated with gastrointestinal
      ulceration and prolonged bleeding. The authors present the distinctive mechanism
      of action for these new COX-2 inhibitors, compare their relative anti
      inflammatory and analgesic properties and describe their safety profile. They
      also summarize indications, contraindications and dosing recommendations.
      CLINICAL IMPLICATIONS: Celecoxib and rofecoxib are valuable dental therapeutic
      agents for the management of inflammatory joint disorders and associated chronic
      orofacial pain. Additionally, rofecoxib, with its more rapid onset, may be useful
      in treating selected cases of acute postsurgical pain.

PMID- 11315376
TI  - Efficacy of subantimicrobial dosing with doxycycline. Point/counterpoint.
AB  - BACKGROUND: This article addresses the role of subantimicrobial dosing with
      doxycycline, or SDD, in the treatment of chronic periodontitis. The authors
      discuss and debate 10 issues with regard to SDD's utility as an adjunct to
      scaling and root planing. TYPES OF STUDIES REVIEWED: The authors reviewed reports
      of controlled clinical trials that assessed the efficacy of SDD. The main focus
      of this article is data from the U.S. Food and Drug Administration's phase 3
      clinical trial that evaluated the efficacy of SDD in terms of alterations of
      probing depth, clinical attachment levels and disease progression. RESULTS: The
      authors compared data from test groups, which underwent root planing plus SDD,
      with data from control groups, which underwent root planing alone. The mean data
      suggest that SDD provides a defined but limited improvement of periodontal status
      when used in conjunction with scaling and root planing. Furthermore, several in
      vivo studies indicated that a nine-month course of SDD did not cause development
      of drug-resistant bacterial strains or alteration of the subgingival microbiota.
      CLINICAL IMPLICATIONS: Some patients may benefit from SDD. However, there are
      several issues that should be clarified before widespread use of SDD is
      recommended for patients with chronic periodontitis. The evidence indicates that
      suppression of the bacterial challenge, which reduces the host response, is the
      most efficient way to control periodontal diseases.

PMID- 11315377
TI  - Third-molar removal patterns in an insured population.
AB  - BACKGROUND: The authors examined third-molar removal patterns in an insured
      population to see how these patterns compare with recommendations in the
      literature. METHODS: The source of treatment data was insurance claims for
      services rendered from July 1991 through December 1999; it included approximately
      100 million dental procedures provided to about 7.4 million patients from all 50
      states. The insured were public and private employees or retirees and their
      dependents. RESULTS: The authors found that third molars were the most commonly
      extracted permanent teeth, and they most often were removed from adolescents.
      Friday was the day of the week on which most extractions occurred, and the
      favored month was August, followed by July, December and June. Another important
      pattern revealed by the authors' analysis was that there was substantial
      variation among dental practices in whether patients had third molars removed and
      in the timing of the removal. They found that adolescent patients in some dental
      practices rarely were referred for third-molar removal, while in other practices,
      most or all had third molars removed. CONCLUSIONS: Third-molar removal patterns
      suggest that many third molars are not removed in response to acute pathology,
      and the observed variation in the likelihood and timing of these extractions
      reflects the lack of consensus on this topic in the dental literature. CLINICAL
      IMPLICATIONS: The apparent lack of consensus on third-molar removal should be
      resolved for the profession to maintain the confidence of the public that the
      recommended care is based on sound evidence.

PMID- 11315378
TI  - The relationship between clinical and MRI findings in patients with unilateral
      temporomandibular joint pain.
AB  - BACKGROUND: With the advent of magnetic resonance imaging, or MRI, clinicians and
      researchers have sophisticated techniques by which to assess the anatomy of the
      temporomandibular joint, or TMJ. Imaging is indicated when the results will
      affect the patient's care beyond that which can be gained from a complete
      clinical assessment. One of the primary indications for treatment of patients
      with temporomandibular disorders, or TMDs, is jaw pain, including TMJ pain.
      Therefore, it is necessary to assess whether MRI-depicted TMJ findings are
      associated with TMJ pain. This study assessed the relationship between TMJ pain
      and clinical and MRI findings. METHODS: Subjects consisted of 85 patients with
      unilateral jaw pain in the area of the TMJ. The contralateral, nonpainful TMJ
      served as the matched control. All patients underwent a complete stomatognathic
      examination that included palpation of both TMJs. No care was given and no anti
      inflammatory medications were prescribed until bilateral MRIs were obtained
      within one week. RESULTS: The authors found significant relationships between the
      side of reported jaw pain and the patient's report that palpation of the TMJ was
      painful and between the side of reported pain and the presence of MRI-detected
      effusions. The authors found no relationship between the side of reported pain
      and the presence of a disk displacement, or DD, or between the presence of
      effusions and DD on either side of the jaw. CONCLUSION: Although MRI-depicted
      effusions of the TMJ were associated with reports of TMJ pain, there was a high
      level of false-positive and false-negative findings. The results indicate that
      palpation of the TMJ is more accurate than MRI-depicted effusions in identifying
      the TMJ as the source of pain for patients with unilateral jaw pain. CLINICAL
      IMPLICATIONS: The results of this study suggest that palpation of the TMJ is
      superior to MRI in identifying the joint as the source of pain. Therefore, the
      most cost-effective and valid test to determine if the TMJ is a source of jaw
      pain is a complete clinical assessment.

PMID- 11315379
TI  - Restorative pulpal and repair responses.
AB  - BACKGROUND: Each year, about 90 million new restorations are placed in the United
      States and 200 million are replaced. Controversy surrounds the pulpal reactions
      and frequency of bacterial microleakage associated with common restorative
      materials. The authors investigated and compared pulpal reactions to different
      types of restorative materials. METHODS: Two hundred seventy-two teeth with
      standardized rectangular Class V unexposed cavities were restored with resin
      based composite bonded to dentin; resin-based composite bonded to enamel; resin
      modified glass ionomers, or RMGI; amalgam lined with zinc polycarboxylate, or
      ZnPC; amalgam lined with calcium hydroxide, or Ca(OH)2; or zinc oxide-eugenol, or
      ZnOE. Teeth were extracted for orthodontic reasons between 20 and 381 days later.
      The authors categorized pulpal responses according to standards set by the
      Federation Dentaire Internationale and the International Organization for
      Standardization. Bacteria were detected using Brown-Brenn-stained sections.
      Pulpal responses were evaluated using histomorphometric analysis and analysis of
      variance statistics. RESULTS: The results showed that RMGI was the best material
      for preventing bacterial microleakage, and resin-based composite bonded to enamel
      was the worst. In regard to minimizing pulpal inflammatory activity, ZnOE was the
      best material and resin-based composite bonded to enamel was the worst. In terms
      of maximizing odontoblast survival beneath deep cavity preparations, Ca(OH)2, was
      the best material and RMGI was the worst. CONCLUSIONS: The results show that
      bacterial microleakage, pulpal injury and repair responses varied widely with
      different restorative materials. CLINICAL IMPLICATIONS: The authors recommend
      that RMGI be used to restore teeth with cavities that are shallow to moderate in
      depth, with the floor of deep cavities being lined with Ca(OH)2 before the teeth
      are restored with RMGI.

PMID- 11315380
TI  - The presence of hepatitis A antibodies in dental workers. A seroepidemiologic
      study.
AB  - BACKGROUND: The licensing of hepatitis A vaccine in the United States and other
      countries in the 1990s raised the question of vaccine candidates. The authors
      undertook a study to evaluate the presence of antibodies against hepatitis A
      virus, or HAV, in dental workers. METHODS: The authors recruited 115 members of
      the dental staff of Tel Aviv University: 82 dentists, 21 dental assistants, eight
      dental hygienists and four laboratory technicians. The subjects completed a
      structured questionnaire regarding demographic information (such as age, sex,
      number of siblings, number of children) and occupational characteristics. Venous
      blood was obtained and examined for presence of immunoglobulin G antibodies to
      HAV by microparticle enzyme immunoassay. RESULTS: Univariant analysis (chi 2 and
      Student t test) and multivariate stepwise logistic regression analysis were used
      to identify variables that were associated with seropositivity. Greater number of
      years of occupation in dentistry were independently and significantly (P = .0004)
      associated with seropositivity to HAV. The calculated odds ratio showed that each
      year of work increased the likelihood of being seropositive by 1.06 (6 percent).
      Subjects tended to have higher seropositive rates if they were older, had a
      greater number of children, had a greater number of siblings, had worked in
      hospitals and worked with children (pediatric dentists and orthodontists).
      CONCLUSIONS: This study suggests that HAV can be considered a hazard to dental
      workers, with risk increasing as the number of years in dentistry increases. More
      studies with larger sample sizes are needed. CLINICAL IMPLICATIONS: As HAV
      infection is associated with morbidity and mortality, dentists--especially those
      working in areas of endemic HAV (such as Africa, Asia and Latin America)--are
      encouraged to consider receiving the active vaccine to prevent HAV infection.

PMID- 11315381
TI  - Avoiding malpractice for nondental conditions. The example of human
      immunodeficiency virus.
AB  - BACKGROUND: Dentists are legally liable for failing to recognize medical
      conditions that they identify while providing dental care and for failing to
      refer patients for follow-up care and testing. This article suggests ways to
      avoid liability using human immunodeficiency virus, or HIV, infection as an
      example. TYPES OF LITERATURE REVIEWED: The authors conducted a review of the
      legal literature to determine circumstances that would cause dentists to have
      legal liability for failing to recognize a medical problem. The authors also
      conducted a review of the dental literature to identify the most common signs of
      HIV infection that dentists might see in practice. RESULTS: The legal literature
      indicates that dentists can be held liable for failing to recognize medical
      problems, including HIV and acquired immunodeficiency syndrome. The dental
      literature shows that there are multiple signs and symptoms that indicate the
      potential for HIV infection to be the underlying cause of many oral diseases.
      PRACTICE IMPLICATIONS: Dentists should be familiar with the most common oral
      manifestations of medical conditions that are likely to be identified in the
      dental office, including those associated with HIV infection. They must recognize
      medical conditions and arrange for appropriate referral to avoid liability.

PMID- 11315382
TI  - Dental clinical attire and infection-control procedures. Patients' attitudes.
AB  - BACKGROUND: The authors surveyed adults in military and civilian dental practices
      about infection-control procedures and clinical attire to see if patients'
      attitudes had changed with the alteration of infection-control procedures over
      the last two decades. METHODS: The authors surveyed 1,500 adults, using a written
      questionnaire at two military hospital dental practices and at four civilian
      dental offices, which included two general practices, one periodontal practice
      and one orthodontic practice. RESULTS: The authors found that the use of name
      tags and patient safety glasses during treatment were preferred by 52.0 percent
      and 53.4 percent, respectively, of respondents in military facilities.
      Respondents had no preference about dentists' clothing, use of protective glasses
      for examinations or head cover use. A majority of respondents preferred that
      dentists wear glasses when performing treatment (54.1 percent), and 77.4 percent
      of respondents preferred that dentists wear masks when providing their care.
      Respondents preferred the use of plastic barriers, and 63.0 percent said it made
      them feel confident that proper infection-control procedures were followed. A
      majority of respondents (52.3 percent) said they would be concerned if barriers
      were not used. CONCLUSIONS: Military and civilian respondents had similar
      perceptions of infection-control procedures. Respondents said they preferred that
      dentists wear name tags in group practices and use masks and protective glasses
      when performing treatment. The use of plastic barriers made respondents feel
      confident that proper infection-control procedures were being followed. PRACTICE
      IMPLICATIONS: This study can be used by dental practices to review their
      infection-control procedures and how patients perceive them. Dentists may decide
      to implement some of these procedures, especially those that are not required,
      and that improve customer satisfaction.

PMID- 11315383
TI  - Patient solicitation and the First Amendment. Protection of 'commercial speech'
      at issue in court cases.

PMID- 11315384
TI  - We've come a long way folks!

PMID- 11315385
TI  - Look at the evidence.

PMID- 11315386
TI  - Caveat emptor.

PMID- 11315388
TI  - Tobacco or health.

PMID- 11315387
TI  - Caveat emptor.

PMID- 11315389
TI  - Tobacco products and health.

PMID- 11315390
TI  - Tobacco: the role of health professionals in smoking cessation. Joint statement.

PMID- 11315391
TI  - Tobacco cessation: isn't it time for dentistry to become more involved?

PMID- 11315392
TI  - Addressing oral disease--the case for tobacco cessation services.
AB  - There is strong scientific evidence from clinical and epidemiological studies
      that tobacco use, particularly cigarette smoking, is linked to periodontal
      disease as well as other serious but less common oral health diseases. Given the
      strength of this evidence, dentists must include tobacco cessation services (TCS)
      as part of their routine care. This paper describes barriers to the adoption of
      TCS as identified by Alberta dentists participating in a randomized intervention
      trial and discusses strategies for overcoming these barriers. As well,
      suggestions are made to professional associations and educational institutes on
      ways to increase the incorporation of tobacco cessation into professional
      practice standards.

PMID- 11315393
TI  - Tobacco-use cessation programs and policies at the University of Manitoba's
      faculty of dentistry.
AB  - The deleterious effects of tobacco use on general health and oral health are well
      documented. While one-third of Manitobans are current smokers, up to 79% report
      they want to quit. Counselling by health care professionals can help achieve quit
      rates of 15-20%. Yet many health professionals do not provide tobacco-use
      cessation counselling because they feel they are not trained to do so. In 1998,
      the faculty of dentistry of the University of Manitoba implemented a number of
      tobacco-use cessation interventions in its undergraduate curricula and general
      teaching clinic. The faculty has also successfully obtained the inclusion of a
      dental fee code for tobacco-use cessation services in the provincial fee guide
      and has received approval to allow dentists who have completed an approved course
      in tobacco-use cessation training to prescribe bupropion HCl (Zyban), in
      consultation with a patient's physician, to aid smoking cessation.

PMID- 11315394
TI  - A practical guide to tobacco cessation in dental offices.
AB  - Tobacco use is an important risk factor for advanced periodontitis, poor response
      to periodontal therapy, oral neoplasms, and dental implant failure. Given the
      effect of tobacco use on oral health, the dental office may be an ideal place for
      tobacco cessation intervention, especially since a large proportion of smokers
      visit their dentist on a regular basis. This paper reviews various tobacco
      cessation strategies for the dental office and provides practical information on
      assessing patients' readiness to quit and choosing appropriate tobacco cessation
      interventions.

PMID- 11315395
TI  - [Urinary iodine levels within normal range in German school-age children].
AB  - BACKGROUND: Recent regional investigations have shown that the abolition of the
      requirement to declare iodine in foodstuffs and the greater emphasis on
      information about goitre prevention led to an increase in urinary iodine
      excretion in Germany. There was also a decrease in thyroid size and goitre
      prevalence in children. No up to date results for the whole of Germany are
      available. PROBANDS AND METHODS: In 1999 we examined the urinary iodine excretion
      in the spontaneous morning urine of 3,065 healthy 6- to 12-year-old school
      children in 128 places from all over Germany. The iodine was measured by the Cer
      arsenit method. RESULTS: The median iodine excretion amounted to 148
      micrograms/l. There were no significant differences between age groups, sexes or
      regions. 73% had no iodine deficiency (> 100 micrograms/l). In 20% the deficiency
      was slight (50-99 micrograms/l), in 6% moderate (20-49 micrograms/l) and in 1%
      there was a severe iodine deficiency (< 20 micrograms/l). 8% excreted > 300
      micrograms iodide per liter urine. CONCLUSION: According to the WHO guidelines,
      there is no longer a iodine deficiency in Germany--at least among children prior
      to puberty.

PMID- 11315396
TI  - [Direct evidence of cytomegalovirus in coronary atheromas of patients with
      advance coronary heart artery disease].
AB  - BACKGROUND AND AIM: Experimental and clinical data support an infectious cause of
      atherosclerosis and thereby coronary artery disease. This study was intended to
      assess the prevalence and possible clinical associations of the presence of
      cytomegalovirus DNA within coronary samples from patients undergoing coronary
      artery bypass grafting. PATIENTS AND METHODS: A coronary thrombendatherectomy was
      performed in 53 patients with advanced coronary artery disease. Two samples of
      each atheroma were used for further analysis and pathogen detection. RESULT: In
      30% of patients with advanced coronary artery disease cytomegalovirus DNA was
      detected in coronary samples as assessed by highly sensitive PCR methods. The
      occurrence of the virus within the vessels was characterized by an inhomogeneous
      distribution pattern. CONCLUSION: Due to an increased proportion of restenotic
      lesions and a higher degree of calcification in cytomegalovirus-positive lesions,
      a causative association between the virus presence and mechanisms of restenosis
      post angioplasty is further supported. Antiviral pharmacological interventions to
      prevent restenosis in high-risk patients, however, seem not to be justified by
      the data currently available.

PMID- 11315397
TI  - [Place of hematopoietic stem cell transplantation in the treatment of
      myelodysplastic syndromes].
AB  - CONVENTIONAL TREATMENT: Myelodysplastic syndromes are hematopoietic stem cell
      disorders characterized by peripheral cytopenia, hypercellular bone marrow with
      dysplastic cell morphology and a tendency to evolve into acute myeloid leukemia.
      Supportive treatment with transfusions, antimicrobial agents, hematopoietic
      growth factors and conventional chemotherapy has only palliative character.
      ALLOGENEIC TRANSPLANTATION: Allogeneic hematopoietic stem cell transplantation
      from HLA-matched family or unrelated donors is currently the only potentially
      curative therapy. Outcome is determined by disease-, patient- and treatment
      related features, which will be discussed in this review. AUTOLOGOUS
      TRANSPLANTATION: Autologous transplantation is an alternative approach for
      patients which lack a suitable allogeneic stem cell donor. Autografts should be
      harvested in complete remission after intensive chemotherapy. Reduced treatment
      related mortality is accompanied by increased risk of relapse. FUTURE DIRECTIONS:
      Clinical trials are currently evaluating dose-modified preparative regimens with
      decreased toxicity, which offer transplantation options also to older patients or
      patients with comorbidities.

PMID- 11315398
TI  - [Biochemical markers of ischemic and non-ischemic myocardial damage].
AB  - BACKGROUND: Biochemical markers have been an integrative part of non-invasive
      diagnostic strategies in cardiology for nearly 50 years, experiencing a
      renascence by the recently acknowledged prognostic potential of cardiac troponins
      in acute coronary syndromes. DIAGNOSIS: According to the guidelines of the
      National Academy of Clinical Biochemistry and the International Federation of
      Clinical Chemistry cardiac troponin T and cardiac troponin I should be considered
      as the new "gold markers" of ischemic myocardial injury. One characteristic
      feature of these new markers is the improved diagnostic potential, reflected by
      the choice of two cut-off values to distinguish minor myocardial injury from
      acute myocardial infarction. In addition, cardiac troponins allow risk
      stratification in the clinical setting of acute coronary syndromes: approximately
      threefold higher mortality rate for patients with rest angina or ST segment
      elevation and cardiac troponin elevation on admission. Other indications for
      cardiac marker analysis are monitoring of therapeutic success in case of invasive
      and non-invasive reperfusion strategies and non-invasive diagnosis of non
      ischemic myocardial injury (myocarditis, cardiac contusion and chemotherapy).
      CONCLUSION: Biochemical cardiac markers are a useful tool in the diagnosis of
      both ischemic and non-ischemic myocardial injury. Among these, cardiac troponins
      seem to become the gold markers for the new millennium.

PMID- 11315399
TI  - [Endoscopic fluorescence diagnosis of esophageal carcinoma after sensitization
      with 5-aminolevulinic acid].
AB  - BACKGROUND: Barrett's esophagus is a complication of gastroesophageal reflux
      disease (GERD) characterized by specialized columnar epithelium that contains
      goblet cells and replaces the squamous epithelium of the distal esophagus. It is
      found in about 10% of patients with symptomatic reflux disease and more
      importantly has been associated with the development of esophageal cancer.
      Adenocarcinoma arises from dysplasia, which is usually not visible during routine
      endoscopy, therefore extensive random sampling of the entire Barrett's segment
      should be performed with biopsies in the 4 quadrants every 1 to 2 cm and of any
      macroscopic abnormality. CASE REPORT: We report the history of a 60-year-old man
      who was admitted to hospital because of an ulcer in Barrett's esophagus not
      healing despite conservative treatment. He has suffered from gastroesophageal
      reflux disease for more than 30 years and an antireflux surgical procedure had
      not resulted in regression of Barrett's esophagus. However, close surveillance
      could not reveal any dysplastic or malignant lesion. Endoscopic fluorescence
      detection (EFD) after sensitization with 30 mg/kg 5-aminolevulinic acid (5-ALA)
      in this patient demonstrated a selective red fluorescence in a macroscopically
      normal appearing area near the already known ulcer. Biopsies from this
      fluorescent area showed an adenocarcinoma. Esophagectomy confirmed the presence
      of intramucosal adenocarcinoma without lymph node metastases.

PMID- 11315400
TI  - [Electron beam computed tomography of the heart before kidney transplantation.
      Severe coronary disease in a 21-year old woman with nephrocalcinosis due to
      infantile hypercalcemia syndrome].
AB  - BACKGROUND: Cardiovascular diseases are very common in patients with end-stage
      renal disease and are the underlying cause of approximately half the deaths in
      dialysis patients. In those patients vascular calcifications are typically seen
      in the tunica media and therefore represent histopathological changes different
      to those in atherosclerosis. For the evaluation of cardiovascular risk in chronic
      dialysis patients, a method is needed to reliably identify patients who have to
      undergo invasive diagnostics. Coronary artery calcium assessed by electron beam
      computed tomography (EBT) has been suggested to measure the extent of coronary
      atherosclerosis in patients with normal renal function. It might also be of value
      in the stratification of cardiovascular risk in patients with renal failure. CASE
      REPORT: We report the case of a 21-year-old female with end-stage renal disease
      as a result of idiopathic infantile hypercalcemia with nephrocalcinosis and
      extensive vascular calcification. Due to a total atrioventricular block, a 2
      chamber pacemaker had been implanted in 1998. Because of a very high calcium
      score in EBT, depressed left ventricular function in echocardiography, and
      limited physical strength she was sent to coronary angiography. Severe 2-vessel
      coronary artery disease was found and successfully treated by balloon
      angioplasty. She was then listed for renal transplantation. Angiographic 6-month
      follow-up showed an excellent long-term result. CONCLUSION: This case
      demonstrates that coronary artery disease can also be present in young dialysis
      patients. Discrimination of atherosclerotic vascular calcification and tunica
      media sclerosis typical in dialysis patients without hemodynamic effects is
      difficult. EBT allows for the direct detection of coronary calcium. Its extent
      correlates with coronary atherosclerosis and the probability of acute coronary
      syndromes in patients with normal renal function. This evidence has not been
      proved for dialysis patients, yet. However, EBT may be of value in the
      stratification of cardiovascular risk for patients awaiting renal
      transplantation.

PMID- 11315401
TI  - [Ulcerative ileocolitis induced by NSAID therapy].
AB  - HISTORY AND PHYSICAL EXAMINATION: A 67-year-old woman was admitted to our
      hospital for spasmodic abdominal pain, diarrhea, and general weakness. She had
      lost 5 kg of weight over the past few weeks. The patient had a 20-year history of
      chronic analgetic abuse, mainly consuming over-the-counter nonsteroidal anti
      inflammatory drugs (NSAID). EXAMINATION: Laboratory examination was remarkable
      for a low serum albumin (2.3 g/dl), an increased erythrocyte sedimentation rate
      of 70 mm/h, and a profound anemia of 8.5 g/dl. Ultrasound of the abdomen showed
      thickening of the colonic wall and distended colon loops filled with fluid. On
      colonoscopy several ulcerations from the sigmoid to the ileum were seen.
      Histologic examination showed a nonspecific ileocolitis. DIAGNOSIS, THERAPY AND
      CLINICAL COURSE: After cessation of NSAID intake diarrhea stopped within a few
      days. Abdominal pain resolved, anemia improved and the patient gained weight. A
      second colonoscopy revealed healing of the colonic ulcerations. Additional
      examinations regarding differential diagnoses showed no pathological results.
      Clinical course and subsequent clinical and endoscopic controls revealing further
      improvement confirmed the diagnosis of an NSAID-induced ileocolitis. CONCLUSION:
      This patient is a typical example for NSAID-induced colonic ulcerations. It
      should be recognized that NSAID induce ulcers not only in the upper
      gastrointestinal tract. A careful drug history may provide the clue for the cause
      of lower gastrointestinal tract ulcerations.

PMID- 11315402
TI  - [Persistent left vena cava superior].

PMID- 11315403
TI  - [Underrepresentation of women among peer reviewers and textbook authors in
      medicine in Germany].
AB  - BACKGROUND AND OBJECTIVE: A characteristic feature of German science is the
      "disappearance" of women during the different ranks from high-school to
      professorship. The goal of the present study was to determine the proportion of
      women among peer reviewers of the German research council and among editors and
      authors of textbooks in internal medicine. METHODS: The candidate list for the
      election of the peer reviewers of the German research council in November 1999
      was checked for the participation of women. Numbers and proportion of women among
      the reviewer boards for practical medicine, theoretical medicine, biological
      chemistry/biophysics and biology were determined. Textbooks of internal medicine
      in German language were checked for female editors and authors. RESULTS: 1.8% of
      the present reviewers and 4.3% of the candidate reviewers for the election of the
      reviewer board for practical medicine were female. The corresponding numbers for
      the reviewer board for theoretical medicine were 3.2% and 8.2%, respectively. The
      reviewer board for biological chemistry and biophysics had no woman among the
      present reviewers and 2.1% among the candidate reviewers. Corresponding
      proportions for the reviewer board for biology are 18.5% and 13.5%, respectively.
      The average percentage of women among all 4 reviewer boards which are involved in
      biomedical research is 5.4% among the present reviewers and 6.5% among the
      proposed reviewers. A similar situation of underrepresentation of women is
      present among authors of medical textbooks. Among 65 editors and co-editors of 19
      textbooks of internal medicine was no woman at all. Among a total of 1092 authors
      47 women corresponding to 4.3% were found. CONCLUSION: These numbers demonstrate
      that the subject of gender discrimination in higher ranks in medicine and science
      in Germany is far from being solved.

PMID- 11315404
TI  - [Doxycycline--the forgotten antibiotic].

PMID- 11315405
TI  - [Diving medicine].

PMID- 11315406
TI  - [Dangerous marine animals].
AB  - Sea-biological basic knowledge for divers is offered only in special lessons for
      advanced scuba divers. According to statistics, however, five per cent of the
      deadly diving accidents are caused by underwater organisms. This number could be
      reduced to a fraction, by correct behaviour during the dive and after an
      accident. The most frequent accidents with sea animals during water sports are
      not by unprovoked shark attacks, which cause six deaths world-wide per year on
      the average, but turn out with usually well camouflaged sea inhabitants, that do
      not attack humans, rather by their inadvertence coincidentally get in contact
      with it. The various defense instruments of the often small, inconspicuous
      organisms reach from teeth over poison stings, pricks, spines, scalpelles, nettle
      injections and chemical weapons up to poison arrows. Due to that variety of the
      maritime life, the most important representatives of its type are explained
      including severity level of the caused injury or contamination. Both, diagnostic
      position and therapy possibility are described as follows: 1. Porifera (sponge),
      2. Hydrozoa (white weed, yellow flower head), Actinaria (sea anemones), 3.
      Conidae (cone shells), Tridocna (giant clam), octopoda (octopus), 4. Acanthaster
      planci (crown of thorns), Echinodea (sea urchins), Holothurioidea (sea cucumber),
      5. Selachoidei (shark), Batoidei (Ray), Muraenidae (moray), Plotosidae (barbel
      eels), Synanciidae (stonefish), Scorpaenidae (scorpionfish), Pterois (lion fish),
      Sphyraena Spec. (barracuda), Balistidae (triggerfish), Ostracionidae (puffer).

PMID- 11315407
TI  - [Severe decompression sickness in divers].
AB  - The term "decompression illness (DCI)" is a disorder which arises from the
      presence of ectopic gas bubbles following decompression. Scuba diving poses the
      risk of two typically clinical syndromes: decompression sickness (DCS) and
      arterial gas embolism (AGE). DCS results from the formation of gas bubbles in the
      tissues of the body and in the blood due to rapid reduction of the environmental
      pressure. AGE is caused by pulmonary overinflation if the breathing gas cannot be
      exhaled adequately during the ascent. Although the pathophysiological mechanisms
      of these two disorders are quite different, both of them lead to the same result:
      inert gas bubbles that may cause impairment of vital functions due to hypoxia.
      Recognizing the signs and symptoms of DCI is the first step of the therapy. The
      emergency treatment contains: basic life support, advanced life support--if
      necessary, horizontal positioning of the victim, administration of 100%
      normobaric oxygen via face mask or endotracheal tube, rehydration, rapid
      transportation to the nearest emergency department/hyperbaric facility for
      definitive treatment in order to prevent serious neurological sequelae.

PMID- 11315408
TI  - [Medical causes of diving accidents inspite of fitness--hypothermia and
      hyperthermia as risk factors].
AB  - The medical test for diving fitness enables the physician to detect possible risk
      factors and to instruct canidates carefully. In most cases psychical and physical
      stability guarantees safe diving. Despite of fitness a variety of factors may
      cause troubles such as jetlag, temperature differences, intake of drugs, of
      alcohol, lack of training or exhaustion. These factors cause a high risk of
      diving accidents. To prevent accidents divers must be instructed in appropriate
      handling of these factors with special regard to hypothermia and hyperthermia.

PMID- 11315409
TI  - [Marine toxins].
AB  - The consumption of seafood, which is contaminated by toxines of red tides, is a
      common cause of disease in tropic regions. The most important diseases, which are
      caused by red tides are Paralytic Shellfish Poisoning (PSP), Diarrhetic Shellfish
      Poisoning (DSP), Neurotoxic Shellfish Poisoning (NSP), Amnesic Shellfish
      Poisoning (ASP), Ciguatera Fish Poisoning (CFP).

PMID- 11315410
TI  - [Barotrauma in diving].
AB  - Boyle's law is important for the understanding of the pathophysiology of
      barotrauma. Barotrauma--any disease or injury due to unequal pressures between a
      hollow space inside the body and the ambient pressure, or between two spaces
      within the body; examples include arterial gas embolism, pneumomediastinum, and
      pneumothorax. It may affect the lungs, the middle ear, the inner ear, the
      external ear, the eyes, the teeth, the gastrointestinal tract, the skin. Symptoms
      remain the same whether it all happens during ascent or descent.

PMID- 11315411
TI  - [Technology of hyperbaric chambers].
AB  - Technical requirements for hyperbaric chambers are subject to permanent change.
      Medical gas supplies, the chamber hulls, control systems, medical equipment as
      well as the security check-up modalities have been constantly adapted according
      to the most recent technical developments. Moreover, different subtypes of
      hyperbaric chambers such as treatment facilities, chambers used for training
      purposes or facilities set up for primary experimental use require specific
      technical outfit. Keeping in mind some recent tragic accidents in hyperbaric
      facilities, chamber security is of foremost importance. Alarm- as well as
      technical monitoring systems, fire-fighting equipment, deluge systems and
      pressure locks are absolute requirements for any hyperbaric chamber. In chambers
      used for therapeutic purposes the possibility of invasive and noninvasive patient
      monitoring as well as hygienic standards have to be ensured.

PMID- 11315412
TI  - Diving accident management, with special emphasis on the situation in the Red
      Sea.
AB  - Accident management is a concept commonly misunderstood, frequently confused with
      accident treatment. The situation in the Sinai and the Red Sea makes a broad
      definition of the term "management" necessary. Management encompasses the whole
      spectrum: from recognition of the need for a hyperbaric facility, establishing
      one, education of dive center management, instructors, boat skippers and deck
      hands, to actual contingency plans set according to the different geographical
      sites. The essential elements of communication, oxygen first aid, transportation,
      and actual recompression therapy or other treatments and follow-up must be
      included. Furthermore, a link to the international organisations involved with
      diving accident management is an essential and desired backup.

PMID- 11315413
TI  - [Asthma and diving].
AB  - Until recently asthma was considered a contraindication for scuba diving due to
      possible "air trapping" and subsequent barotrauma. However, in view of the wide
      prevalence and heterogeneity of the illness this is no longer justified. There
      are, nevertheless, certain prerequisites for diving with asthma: a complete
      anamnesis and an analysis of the pulmonary function, an exact diagnosis of the
      trigger factors as well as of the bronchial hyperreactivity in order to correctly
      ascertain the asthma level. When scuba diving, asthmatics need to observe certain
      rules. Still, some types of asthma remain incompatible with diving. Among these
      are the pseudo-allergic, exercise-induced, and psychogenic-induced asthma as well
      as allergic bronchopulmonal aspergillosis. Asthma due to bronchial infections and
      GERD are considered relative contraindications.

PMID- 11315414
TI  - [Nocturnal gastroesophageal reflux as a cause of refractory chronic laryngitis-
      pathophysiology and management].
AB  - Chronic laryngitis is a common disease with a multifactoral genesis. One of the
      known causal factors is gastrolaryngeal acid reflux as a consequence of
      gastroesophageal reflux disease (GERD). 10 to 30% of the patients do not show an
      adequate response to the standard treatment with proton pump inhibitors, which
      could not be well explained in the past. Our own observations indicate, that
      sleep related gastroesophageal reflux may play an important role. The special
      physiological conditions in sleep can impair the reflux, and an increased
      nocturnal breathing effort in snoring or sleep apnea induces an intensive
      gastrolaryngeal reflux. This paper explains the pathophysiological background and
      the diagnostics and differential treatment.

PMID- 11315415
TI  - A return to biological thinking in medicine.

PMID- 11315416
TI  - A disease by any other name: musings on the concept of a genetic disease.
AB  - What exactly is a genetic disease? For a phrase one hears on a daily basis, there
      has been surprisingly little analysis of the underlying concept. Medical doctors
      seem perfectly willing to admit that the etiology of disease is typically
      complex, with a great many factors interacting to bring about a given condition.
      On such a view, descriptions of diseases like cancer as genetic seem at best
      highly simplistic, and at worst philosophically indefensible. On the other hand,
      there is clearly some practical value to be had by classifying diseases according
      to their predominant cause when this can be accomplished in a theoretically
      satisfactory manner. The question therefore becomes exactly how one should go
      about selecting a single causal factor among many to explain the presence of
      disease. When an attempt to defend such causal selection is made at all, the
      standard accounts offered (Koch's postulates, Hill's epidemiological criteria,
      manipulability) are all clearly inadequate. I propose, however, an
      epidemiological account of disease causation which walks the fine line between
      practical applicability and theoretical considerations of causal complexity and
      attempts to compromise between patient-centered and population-centered concepts
      of disease. The epidemiological account is the most basic framework consistent
      with our strongly held intuitions about the causal classification of disease, yet
      it avoids the difficulties encountered by its competitors.

PMID- 11315417
TI  - A new model for the origins of chronic disease.
AB  - Living things are often plastic during their early development and are moulded by
      the environment. Many human fetuses have to adapt to a limited supply of
      nutrients, and in doing so they permanently change their physiology and
      metabolism. These programmed changes may be the origins of a number of diseases
      in later life, including coronary heart disease, stroke, diabetes and
      hypertension.

PMID- 11315418
TI  - On the difficulty of defining disease: a Darwinian perspective.
AB  - Most attempts to craft a definition of disease seem to have tackled two tasks
      simultaneously: 1) trying to create a series of inclusion and exclusion criteria
      that correspond to medical usage of the word disease and 2) using this definition
      to understand the essence of what disease is. The first task has been somewhat
      accomplished, but cannot reach closure because the concept of "disease" is based
      on a prototype, not a logical category. The second task cannot be accomplished by
      deduction, but only by understanding how the body works and what each component
      is for, in evolutionary detail. An evolutionary view of the origins of the body
      and its vulnerabilities that result in disease provides an objective foundation
      for recognizing pathology. Our social definition of disease will remain
      contentious, however, because values vary, and because the label "disease"
      changes judgments about the moral status of people with various conditions, and
      their rights to medical and social resources.

PMID- 11315419
TI  - Value neutrality in genetic counseling: an unattained ideal.
AB  - Beginning with a discussion of why value neutrality on the part of the genetics
      counselor does not necessarily preserve autonomy of the counselee, the idea that
      social values unavoidably underlie the articulation of risks and benefits of
      genetic testing is made explicit. Despite the best efforts of a counselor to
      convey "value neutral" facts, risk assessment by the counselee and family is done
      according to normative analysis, experience with illness, and definitions of
      health. Each of these factors must be known by the genetic counselor in order to
      relate those facts which she acknowledges as relevant to the decisions that will
      be made by those people seeking the genetic information. Concisely, the scope of
      this paper includes the role of the genetic counselor in facilitating a family
      planning decision-making process. In the expression of genetic risks, the
      authority of medical language impacts a person's understanding of epidemiological
      data. By claiming that "value neutrality" is an ethos of genetic counselors, this
      implies that there exists a distinction between these scientific facts and
      personal values; this assumption is fallacious and should not be promoted to
      patients as a truth within the professional ethos statement of genetic
      counseling.

PMID- 11315420
TI  - Can it be a "sin" to understand disease? On "genes" and "eugenics" and an
      "unconnected connection".
AB  - Particularly, but not exclusively, in Germany, concerns are uttered as to the
      consequences of modern biotechnological advances and their range of applications
      in the field of human genetics. Whereas the proponents of this research are
      mainly focussing on the possible knowledge that could be gained by understanding
      the causes of developmental processes and of disease on the molecular level, the
      critics fear the beginnings of a new eugenics movement. Without claiming a
      logical relationship between genetic sciences and eugenics movements, it is
      nevertheless suggested in this article that a connection between both can become
      established when the distinction between scientifically validated statements on
      one hand and guiding hypotheses and assumptions on the other hand is blurred, as
      is observed particularly when scientists report their results to the public. This
      claim is demonstrated in comparisons between the current state of scientific
      knowledge on the role of genes in development and causation of diseases, and the
      way this is presented to the public. It is required that a debate on
      biotechnology should include reflections on the validity of claims made by
      scientists.

PMID- 11315421
TI  - Respect for persons, informed consent and the assessment of infectious disease
      risks in xenotransplantation.
AB  - Given the increasing need for solid organ and tissue transplants and the
      decreasing supply of suitable allographic organs and tissue to meet this need, it
      is understandable that the hope for successful xenotransplantation has resurfaced
      in recent years. The biomedical obstacles to xenotransplantation encountered in
      previous attempts could be mitigated or overcome by developments in
      immunosuppression and especially by genetic manipulation of organ source animals.
      In this essay we consider the history of xenotransplantation, discuss the
      biomedical obstacles to success, explore recent developments in transgenic
      sourcing of organs and tissues, and analyze the problem of infectious disease
      resulting from xenotransplantation (xenosis). We then apply a model of risk
      analysis to these risks. The conclusions of this risk analysis are used in an
      ethical evaluation of informed consent in xenotransplantation, with an ethical
      foundation in Kantian autonomy and Levinasian heteronomic alterity. Our
      conclusion is that individual and collective informed consent to the infectious
      disease risks of xenotransplantation requires an open, participatory and
      dialogical public policy process not yet seen in the United States and Europe.
      Until that process is created, we propose caution in xenotransplantation in
      general and a postponement of solid organ xenotransplants in particular.

PMID- 11315422
TI  - Patient autonomy in emergency medicine.
AB  - Theoretical models for patient-physician communication in clinical practice are
      frequently described in the literature. Respecting patient autonomy is an ethical
      problem the physician faces in a medical emergency situation. No theoretical
      physician-patient model seems to be ideal for solving the communication problem
      in clinical practice. Theoretical models can at best give guidance to behavior
      and judgement in emergency situations. In this article the premises of autonomous
      treatment decisions are discussed. Based on a case-report we discuss different
      genuine efforts the physician can do to uncover treatment refusal and respect
      patient autonomy in an emergency situation. Autonomy requires competence and in
      emergency medicine time does not allow intimate exploration of patient competence
      and reasons for treatment refusal. We find that the physician must base her
      decision on a firm theoretical base combined with a practical and realistic view
      of the patient's situation on a case to case basis.

PMID- 11315423
TI  - The relation between medical education and the medical profession's world view.
AB  - Thinking in medicine is still dominated by the cartesian view of science of the
      past centuries, dividing individuals into the reasoning mind (res cogitans) and
      an objective body as part of all non-subjective things of the world (res
      extensa). This classical scientific paradigm does not take into account the
      influence the observer exerts on the observed phenomena. Applying this paradigm
      to medical research and education has consequences regarding the relationship
      between physicians and patients as well as between medical teachers and their
      students. An improvement of medical education towards a broader understanding of
      complex illnesses with their psychosocial implications must be based on
      philosophical and epistemological issues. The requirements of modern medicine
      cannot just be met by adding more psycho-social content to somatic medical
      education or by changing the didactic approach without reflection on the
      underlying concepts and the relation of the human being to his world.

PMID- 11315424
TI  - Teaching science vs. the apprentice model--do we really have the choice?
AB  - The debate about the appropriate methodology of medical education has been (and
      still is) dominated by the opposing poles of teaching science versus teaching
      practical skills. I will argue that this conflict between scientific education
      and practical training has its roots in the underlying, more systematic question
      about the conceptual foundation of medicine: how far or in what respects can
      medicine be considered to be a science? By analyzing the epistemological status
      of medicine I will show that the internal aim of medicine ("promoting health
      through the prevention and treatment of disease") differs from the internal aim
      of science ("the methodological and systematic acquisition of knowledge").
      Therefore, medicine as a whole discipline should not be considered as a science.
      However, medicine can be conceptually and methodologically scientific in so much
      as it is based on scientific knowledge. There is evidence from cognitive science
      research that diagnostic reasoning not only relies on the application of
      scientific knowledge but also--especially in routine cases--on a process of
      pattern recognition, a reasoning strategy based on the memory of previously
      encountered patients. Hence, medical education must contain both: the imparting
      of scientific knowledge and the rich exposure to concrete cases during practical
      training. Hence, the question of teaching science vs. the apprentice model will
      not be "either-or" but rather "both--but in which proportion?"

PMID- 11315425
TI  - The concept of quality of life: legal aspects.

PMID- 11315426
TI  - Considering the "ferrule effect".

PMID- 11315427
TI  - Single-tooth implant restorations: considerations and treatment sequencing.

PMID- 11315429
TI  - Proper gingival retraction for the impression-making procedure.

PMID- 11315428
TI  - The implant periapical lesion: four case reports and review of the literature.
AB  - Postoperative complications have been identified with implant failure in
      conjunction with the increased use of root-type implant restorations. The failure
      of osseointegrated dental implants primarily occurs as a result of peri
      implantitis and occlusal overload. Less frequently reported failures, however,
      have been attributed to implant periapical lesions. The etiology and treatment
      modalities for such lesions have been speculated throughout the literature. This
      article discusses possible etiologies of and treatment for implant periapical
      lesions based on the existing literature and four case reports.

PMID- 11315430
TI  - Fixed provisionalization with transitional implants for partially edentulous
      patients: a case report.

PMID- 11315432
TI  - The art of listening....

PMID- 11315431
TI  - Digital shade analysis and verification: a case report and discussion.
AB  - Shade analysis and selection requires the accurate and objective evaluation of
      hue, chroma, value, characterization, and translucency. Conventional shade
      analysis techniques using shade tabs often result in the subjective analysis and
      miscommunication of color. Digital shade analysis systems have been designed to
      eliminate the subjectivity of color analysis and provide exact information for
      laboratory buildup and fabrication. The advent of digital shade analysis can
      facilitate the precise and uniform fabrication of aesthetic restorations by
      technicians at all levels of color expertise.

PMID- 11315433
TI  - Gingival recession around wide-diameter versus standard-diameter implants: a 3-
      to 5-year longitudinal prospective study.

PMID- 11315434
TI  - A prospective 2-year clinical evaluation of overdentures attached to nonsplinted
      implants utilizing ERA attachments.
AB  - Edentulism is a major oral healthcare issue for an ever-increasing older
      population in the United States. Most previous studies examined the success of
      overdentures supported by splinted implants utilizing clip bars and other types
      of attachments. This longitudinal study of 10 consecutive patients involves
      mandibular overdentures supported by nonsplinted implants with ERA attachments.
      Two-year results indicate that nonsplinted implants can be successfully used with
      ERA attachments to support overdentures. Each patient reported increased
      satisfaction with comfort, chewing, retention, and phonetics with the implant
      assisted ERA-retained overdenture.

PMID- 11315435
TI  - Influence of anatomy on Schneiderian membrane perforations during sinus elevation
      surgery: three-dimensional analysis.

PMID- 11315436
TI  - Computer-guided surgery utilizing a computer-milled surgical template.
AB  - The primary objective of implant placement is to support prosthetic restorations
      that return patients to proper oral form, function, and aesthetics. Since correct
      implant placement can be a technique-sensitive process, it is performed in
      conjunction with various diagnostic and guidance procedures. For accurate
      diagnosis, radiographic templates, computed tomography scans, and surgical
      simulation software are unparalleled. This article demonstrates the manner by
      which computer-guided surgery and computer-milled surgical templates can enable
      precise implant placement for the entire implant team.

PMID- 11315437
TI  - Orthodontically induced gingival and alveolar augmentation: clinical and
      histological findings.

PMID- 11315438
TI  - Caring about each other.

PMID- 11315439
TI  - The frustrated physician.

PMID- 11315440
TI  - Balancing profession and family. Women in medicine.

PMID- 11315441
TI  - Stress impairment in physicians.

PMID- 11315442
TI  - Domestic violence: level of training, knowledge base and practice among Milwaukee
      physicians.
AB  - BACKGROUND: Domestic violence is a prevalent problem with significant health
      consequences. Early recognition and appropriate intervention with referral to
      local domestic violence agencies can be life-saving. Little is known, however,
      about the current level of training, knowledge base and attitudes of physicians
      in this area. METHODS: A survey was sent to 1300 physicians practicing in
      Milwaukee County in the following specialties: Family Practice, Internal
      Medicine, OB/GYN, Psychiatry. Demographic information was obtained. Questions
      were designed to explore attitudes towards domestic violence, frequency of
      encounters with victims or abusers, and knowledge of resources and appropriate
      intervention. RESULTS: Of the 192 respondents, 74% reported having some training
      in domestic violence. Thirty percent reported seeing victims in their practice on
      a daily or weekly basis. Seventy percent feel able to identify a victim of
      domestic violence. Less than a third of respondents screened at least half of the
      patients they see for the possibility of abuse. Less than half always refer
      victims to a hotline or shelter, and less than a quarter of the respondents
      discuss safety plans with victims. A potentially dangerous response is telling a
      victim not to go back to an abuser without providing referrals and safety
      supports. In spite of this, almost a quarter of respondents always tell a victim
      to not go back to the abuser. Family practitioners and psychiatrists were more
      likely to discuss abuse with patients than were internists. CONCLUSION:
      Significant numbers of physicians, in Milwaukee County, practicing certain
      specialties that potentially have a high rate of contact with domestic violence
      victims have had insufficient training in domestic violence assessment and
      intervention. Physicians should be familiar with the domestic violence hotlines
      and shelters in their communities and need to incorporate screen questions for
      domestic violence into their regular practice.

PMID- 11315443
TI  - Health behavior counseling at annual exams.
AB  - OBJECTIVE: To determine if patients expected and desired health behavior
      discussions at annual exams, and if these discussions motivated high-risk
      patients to modify a health behavior. METHODS: 1213 patients seen for an annual
      exam at Gundersen Clinic were sent a survey. Patients were asked if discussions
      about weight, exercise, tobacco use and stress occurred at their exam. Patients
      were also asked if the discussions were expected and desired and if the
      discussions motivated them to modify a health behavior. RESULTS: 571 surveys were
      returned. Over 50% of high-risk patients for each health behavior had a
      discussion. Patients who were overweight, obese, smoked or had excess stress were
      more likely to want and expect discussions than lower risk counterparts. Obese
      and overweight patients were also more likely to report being motivated to
      maintain or lose weight. CONCLUSION: Patients in need of weight, smoking and
      stress management counseling expected and desired behavior discussions and were
      motivated to modify their behavior.

PMID- 11315444
TI  - Accuracy of clinical variables in the identification of radiographically proven
      constipation in children.
AB  - STUDY OBJECTIVE: To determine whether clinical variables accurately identify
      children with radiographically proven constipation. METHODS: Prospective, cross
      sectional case series of children 2-12 years of age with abdominal pain (AP)
      requiring radiographic evaluation. Constipation was defined radiographically as
      the presence of fecal material throughout the colon. The presence of other
      pathology was noted. The pediatric emergency department (ED) physicians recorded
      a comprehensive history and physical examination and a provisional diagnosis was
      made. Radiographs were initially interpreted by the pediatric ED attending
      physicians; the official interpretation was later provided by a single board
      certified pediatric radiologist who was blinded to the ED interpretation. A
      discriminant analysis was performed to identify variables that could best
      discriminate between patients with, and without, radiographically proven
      constipation. RESULTS: In total 251 patients were enrolled over a 12 month
      period. Four variables were noted to be more common in constipated patients: a
      history of normal or hard stools, absence of rebound tenderness, presence of
      tenderness in the left lower quadrant and stool in the rectal vault on exam.
      Stool present on rectal exam was the best discriminator between patients with and
      without constipation. The discriminant analysis model had a sensitivity of 77%,
      specificity of 35% and a negative predictive value of 55%. CONCLUSION: No
      clinical variable, either as a single variable or in a model, accurately
      identified patients with abdominal pain and radiographically proven constipation.

PMID- 11315445
TI  - Folliculitis keloidis nuchae.
AB  - Keloid scars are an idiopathic result of cuts, bruises, lacerations and often
      from surgical incisions. Medical therapy has been used with some results, but
      often surgical excision is necessary when the keloids are located in areas of
      exposed skin. Often skin grafting is necessary. The problem of keloid formation
      is more common in African Americans and Asians in the United States. Because
      surgery of these lesions is sometimes considered cosmetic by HMOs and other
      insurance carriers, there exists a dispute between the medical profession and
      insurance carriers regarding the medical necessity of surgery. We have operated
      on many keloids in our practice; however, the case report we are presenting is a
      unusual and rare case of giant keloid formation requiring extensive surgery and x
      ray therapy.

PMID- 11315446
TI  - Covenants not to compete in Wisconsin: a general overview.

PMID- 11315447
TI  - Increasing the use of ACE inhibitors in heart failure treatment.

PMID- 11315448
TI  - The evolution of care for the chronically critically ill patient.
AB  - The post acute health care system has evolved its infrastructure to accommodate
      the growing complex medical patient population, a direct result of the expanded
      capability in supporting critically ill patients in the ICU setting. When
      patients fail to wean from mechanical ventilation in the ICU, there is often less
      emphasis on continuing these efforts, and patients appear better served in
      specialized units dedicated to weaning patients from mechanical ventilation. Long
      term acute care hospitals also provide an ideal environment to support patient
      care for other complex medical illnesses, including populations with oncologic,
      cardiovascular, and infectious disease. The LTAC hospital seems best adapted to
      this role. Its infrastructure includes significant physician support and the
      blending of immediate and long-term care services and provides an ideal
      opportunity to serve this resource-intensive group. An emphasis on the transition
      from acute illness to recovery serves to define the role and mission of this
      important entity and highlights the specialized nature of the LTAC hospital.

PMID- 11315449
TI  - Management of venous thromboembolic disease in the chronically critically ill
      patient.
AB  - Although PE is the most common preventable cause of death among U.S. hospital
      patients, proper treatment of thromboembolism and adequate prophylaxis in high
      risk patients have been shown to be effective in saving lives. Because clinical
      symptoms and signs of thromboembolic disease are often nonspecific, early
      diagnosis and treatment rely on the capacity of physicians to adequately identify
      a patient at risk, choose the appropriate diagnostic modalities in a cost
      effective fashion, and promptly initiate treatment. The diagnosis of VTE is
      particularly challenging in patients who are in the post acute period of a
      complex medical or surgical illness. Avenues that need to be further explored
      include various diagnostic tests such as spiral CT, MR imaging, and
      transesophageal echocardiography, which are less invasive than the present gold
      standard of pulmonary angiography. Also needed are better clinical data regarding
      the optimal choice of preventive therapy (e.g., unfragmented heparin or LMWH or
      mechanical devices) and clinical outcome of such therapy in patients with
      prolonged illness.

PMID- 11315450
TI  - The evaluation and management of hypoxemia in the chronic critically ill patient.
AB  - Hypoxemia is a prevalent problem in the chronically critically ill patient. This
      article reviews the pathophysiologic mechanisms of hypoxemia in this patient
      population, discusses how oxygenation is evaluated, and reviews methods for
      delivery of oxygen. Other topics directly related to oxygen use, such as oxygen
      toxicity, heliox use, and portable oxygen devices, are included.

PMID- 11315451
TI  - Weaning from prolonged mechanical ventilation.
AB  - The development of weaning failure and need for PMV is multifactorial in origin,
      involving disorders of pulmonary mechanics and complications associated with
      critical illness. The underlying disease process is clearly important when
      discussing mechanisms of ventilator dependence; interventions therefore must be
      tailored to individual patients. Unfortunately, the main conclusion that can be
      drawn from the sum of the studies investigating patients on PMV to date is that
      an evidence-based approach to weaning is not possible and more research needs to
      be done. New studies need to incorporate severity-of-illness scores and an
      assessment of principal and comorbid conditions to allow for comparison of the
      findings from different centers. The best approach to a patient requiring PMV
      after exclusion of easily treatable conditions is not known. The literature
      regarding both acute and chronic cases suggests that a systematic approach to
      weaning involving the participation of multiple caregivers, including nurses,
      physicians, and respiratory, physical, and speech therapists facilitates
      liberation from MV. Although a gradual decrement in ventilator support would seem
      prudent, Scheinhorn et al have begun to identify a subpopulation of patients who
      can tolerate an acceleration of the weaning process. Given the known
      complications associated with MV, it is crucial that further research be
      performed to identify patients as soon as they are capable of breathing
      spontaneously. The literature demonstrates through multiple studies that
      satisfactory patient outcomes are attainable and can be achieved at LTAC
      facilities in a more cost-effective manner than in an ICU setting. The trend
      toward the concentration of patients into specialized regional weaning centers
      should facilitate the research process and continue to improve outcomes in this
      population.

PMID- 11315452
TI  - Gastrointestinal problems in the chronically critically ill patient.
AB  - In summary, a variety of gastrointestinal processes may occur in the chronically
      critically ill patient population, usually as consequence of the primary systemic
      process. The clinical presentation is frequently nonclassic and there often is a
      substantial delay in diagnosis, resulting in increased morbidity and mortality.

PMID- 11315453
TI  - Nutrition in chronic critical illness.
AB  - Nutritional management of patients with respiratory failure can be a model of
      nutritional management in chronically critically ill patients. This model
      requires recognition of the differing metabolic states of starvation and
      hypermetabolism. Starvation can result in malnutrition, with adverse effect on
      respiratory muscle strength, ventilatory drive, and immune defense mechanisms.
      General nutritional goals include preservation of lean body mass by providing
      adequate energy and positive nitrogen balance. General nutritional prescriptions
      for both states include a substrate mix of 20% protein, 60% to 70% carbohydrates,
      and 20% to 30% fat. Positive nitrogen balance is difficult to attain in
      hypermetabolic patients and energy requirements are increased compared with
      starved patients. Enteral nutrition should be the mode of initial nutrient
      delivery unless the gastrointestinal tract is nonfunctional. Monitoring of
      nutritional support is essential. Complications of nutritional support are
      multiple. Nutritional hypercapnia is an important complication in a chronically
      critically ill patient. Outcomes of selected long-term acute patients are poor,
      with only 8% of patients fully functional 1 year after discharge. Appropriate
      nutritional therapy is one aspect of management of these patients that has the
      possibility of optimizing function and survival.

PMID- 11315454
TI  - Acute renal failure and dialysis in the chronically critically ill patient.
AB  - Acute renal failure is a common clinical problem in the intensive care unit (ICU)
      and is associated with significant morbidity and mortality. There is no "magic
      bullet" to prevent acute renal failure or to modify the clinical course of
      established renal failure. The approach to therapy is directed to the early
      initiation of dialysis therapy. Continuous dialysis therapy is becoming the
      preferred form of dialysis in the ICU.

PMID- 11315455
TI  - Cardiologic problems in the post acute ventilated patient.
AB  - Chronically critically ill patients who develop acute respiratory failure
      commonly have complicating cardiac pathology that may or may not be evident at
      initial evaluation. The acute coronary syndromes should be excluded in all
      patients presenting with respiratory failure. Cardiac rhythm disturbances are
      common and should be actively investigated and treated in all critically ill
      patients. Heart failure is common in the chronically critically ill patient but
      usually responds to early diagnosis and prompt treatment. Finally, cardiogenic
      shock carries a poor prognosis in most patient subsets except when it is caused
      by cardiac tamponade. The intensivist must be vigilant for cardiac pathology
      complicating the recovery of patients with acute respiratory illness and initiate
      the search for correctable problems that may precipitate further episodes of
      respiratory insufficiency.

PMID- 11315456
TI  - Endocrine problems in the chronically critically ill patient.
AB  - The endocrine adaptations to critical illness are varied. In the diabetic
      patient, counterregulatory hormones predispose to insulin resistance and
      hyperglycemia, a derangement accentuated by the use of glucocorticoids and
      enteral or parenteral nutrition. Thyroid abnormalities include the euthyroid sick
      syndrome, which may manifest as a low T3, low T4, low TSH, or all three. Illness
      in patients with pre-existing hypothyroidism or hyperthyroidism may precipitate
      myxedema coma or thyroid storm, respectively. The most important issue related to
      calcium is that of acute hypercalcemia, which, in the intensive care unit,
      usually is caused by malignancy and dehydration. Hyponatremia, a frequently
      encountered electrolyte disturbance, is evaluated best and treated according to
      volume status.

PMID- 11315457
TI  - Ethical issues in the chronically critically ill patient.
AB  - The chronically critically ill are a challenging population of patients. Their
      mortality rate is high and expected functional status is low. The physician
      responsible for the care of these patients often is conflicted because the gains
      experienced by these patients may be small or absent whereas the pressure by
      society to use medical resources better is great. This pressure leads to the need
      for making difficult decisions on issues ranging from the initiation of acute
      care to withholding and withdrawing of care at the end of life. By understanding
      the ethical principles that govern decision-making, the physician can guide
      patients and their families toward realistic expectations.

PMID- 11315458
TI  - Noninvasive mechanical ventilation for post acute care.
AB  - The increasing use of NPPV in both acute and chronic settings has added to
      ventilator options in the post acute setting. Some patients start NPPV during
      their acute presentation and continue use during their post acute stay. Others
      are difficult to wean from invasive mechanical ventilation, and, if selected
      carefully, can be extubated and weaned using NPPV. Still others may initiate NPPV
      in the post acute setting with the anticipation of long-term use. In any care
      settings, principles of patient selection and management in monitoring practices
      overlap considerably. Noninvasive ventilation has been shown to reduce morbidity,
      mortality, and hospital stay in the acute setting for selected patients, and
      almost certainly prolongs survival for patients with restrictive thoracic
      disorders in the chronic setting. Although efficacy studies have not been
      performed in the post acute setting, it is reasonable to anticipate that
      appropriate use of NPPV will yield similar benefits. Accordingly, clinicians
      working in the post acute setting must acquire skill and experience in the proper
      application of NPPV to optimally manage the increasing number of patients treated
      with NPPV in this expanding arena.

PMID- 11315459
TI  - Tracheostomy management in the chronically ventilated patient.
AB  - Tracheotomy is a fundamentally important technique for managing patients who
      require long-term mechanical ventilation. Appropriate application of tracheotomy
      requires a skilled approach for timing the procedure, selecting the appropriate
      tracheostomy tube appliance, caring for the artificial airway once it is in
      place, and assisting patients with their specialized needs, such as articulated
      speech, airway humidification, and oral nutrition. Preparing patients for airway
      decannulation after they have weaned from mechanical ventilation requires a
      similar level of skill and attention to detail.

PMID- 11315460
TI  - Respiratory infection in the chronically critically ill patient. Ventilator
      associated pneumonia and tracheobronchitis.
AB  - The long-term ventilated patient is at high risk for developing nosocomial
      pneumonia or tracheobronchitis. In general, the frequency of infection increases
      with the duration of mechanical ventilation, but the risk appears to be greatest
      in the first week of intubation. Although these types of infection are common and
      may have morbidity and mortality impact, the daily risk is less in the long-term
      ventilated patient than in the acutely ill intubated patient. This reduced daily
      risk may reflect a "survivor effect," with less healthy patients dying early in
      the hospital stay and not surviving long enough to undergo tracheostomy and long
      term ventilation. A number of factors predispose these patients to infection,
      including host defense impairment and exposure to large numbers of bacteria. This
      exposure can occur through the airway, and proper care of respiratory therapy
      devices is essential to minimize the risk for infection. Most infections of the
      lower respiratory tract are preceded by airway colonization with EGN bacteria
      and, with improvement in host defenses and nutrition, infection in the face of
      colonization is less likely. In some patients, colonization can be eliminated.
      When the long-term ventilated patient does develop infection, it generally
      involves highly resistant gram-negative or gram-positive organisms and therapy
      should be prompt and appropriate. Not all such patients respond to systemic
      antibiotics, and the use of adjunctive aerosol therapy may have benefit for those
      with either tracheobronchitis or pneumonia, especially if highly resistant
      pathogens are present.

PMID- 11315461
TI  - Antimicrobial resistance in the chronically critically ill patient.
AB  - Infection caused by organisms resistant to conventional antimicrobial therapy is
      an emerging problem of global proportions. This article describes the
      epidemiology of infections caused by resistant organisms in chronically
      critically ill patients and explores factors and mechanisms that lead to the
      development of resistance. Specific organisms and strategies for the treatment
      and control of these resistance organisms are discussed.

PMID- 11315462
TI  - Transmission of wild poliovirus type 2--apparent global interruption.

PMID- 11315463
TI  - Imported human outbreak of trichinellosis, Italy.

PMID- 11315464
TI  - Federal Nursing Service Award. Impact of TriCare/managed care on total force
      readiness.
AB  - Mission readiness is dependent on a healthy total force and the response of
      military medical and nursing services. Managed care has become the norm in U.S.
      health care, including the Department of Defense Military Health System. Cost
      management, health maintenance organizations, and other health plans are defined
      as "managed care," an aggressive cost-control effort by health care purchasers
      and insurers to limit health care spending and services and advance a market
      oriented, profit-driven system. The impact of managed care on mission readiness
      and retention of active and reserve personnel is and will continue to be
      profound. The purpose of this research was to conduct a qualitative,
      phenomenological study (life experiences) of TriCare/managed care to explore the
      impact and the meaning of the experience on total force mission readiness of the
      U.S. Air Force and how managed care has changed nursing practice. The results
      reveal the significance of the impact of TriCare/managed care on total force
      readiness by identifying, through themes, meta-themes, and a representative
      model, the negative effect that economics is having on active duty and reserve
      force health and well-being.

PMID- 11315465
TI  - New York Chapter History of Military Medicine Award. U.S. Army medical
      helicopters in the Korean War.
AB  - Medical evacuation helicopters are taken for granted in today's military.
      However, the first use of helicopters for this purpose in the Korean War was not
      done intentionally but as a result of the necessity of moving patients rapidly
      over difficult Korean terrain and of the early ebbing of the main battle line.
      The objective of this essay is to increase the historical awareness of military
      medical evacuation helicopters in the Korean War during this 50th anniversary
      year. By describing the many challenges and experiences encountered in
      implementing the use of helicopters for evacuation, the reader will appreciate
      how a technology developed for another use helped in the success of evacuating
      nearly 22,000 patients while contributing to establishing a mortality rate of
      wounded of 2.4%. The preparation to write this essay included archival research
      of historical reports, records, and oral histories from the archives of the U.S.
      Army Center for Military History. Additionally, a search of journal articles
      written during and after the Korean War was conducted. The result is a
      comprehensive description of the use of medical evacuation helicopters in the
      Korean War.

PMID- 11315466
TI  - Mary J. Nielubowicz Essay Award. Population-based needs assessment in the design
      of patient education programs.
AB  - The population-based needs assessment discussed in this paper was conducted as
      part of a larger study evaluating the status of the patient and family education
      program at a military treatment facility. The purpose of the assessment was to
      describe the congruence of patient epidemiologically defined educational needs
      with patient education program offerings. A seven-step theoretical framework for
      conducting population-based needs assessments by Declercq, Bichell, and Center
      guided data collection and data analysis. Results of the analysis were used to
      provide evidence-based guidance to the military treatment facility's Executive
      Steering Council on improving patient health care outcomes through redesign and
      institutionalization of the patient education program. The population-based needs
      assessment provides a viable avenue for delineation of disease patterns,
      prioritization of health education needs, and design of effective patient
      education, health promotion, and disease prevention programs in support of the
      Department of Defense Military Health System Optimization Plan.

PMID- 11315467
TI  - The philanthropic string: medical aspects of military strategy.
AB  - Since antiquity, medical care has played an important role in both military
      strategy and conflict resolution. Although this is usually a negative and an
      unintended event, medical care can be a positive and a rational alternative to
      present-day weapons of mass destruction. Yet, military and civilian planners have
      not traditionally accepted, recognized, and used a "philanthropic string."
      Nevertheless, medical care can be an important factor in resolving international
      conflict, either in support of military operations or as a separate function.
      Therefore, it is timely, and pragmatic, to include humanitarian medical care in
      strategic military planning.

PMID- 11315468
TI  - Evaluation of a sexually transmitted disease/human immunodeficiency virus
      prevention train-the-trainer program.
AB  - In this study, a behavioral intervention known as the STD/HIV Intervention
      Program (SHIP) was implemented at the Navy preventive medicine technician (PMT)
      school as a "train-the-trainer" course. Course evaluation questionnaires were
      administered to PMT students immediately after the training. Follow-up interviews
      evaluating the SHIP course were conducted with PMTs (N = 73) 1 year after the
      training. PMT students were fairly satisfied with SHIP overall, as well as with
      specific components of the course. As hypothesized, the SHIP train-the-trainer
      course was considered useful by most PMTs in their first duty assignments after
      completing PMT school.

PMID- 11315469
TI  - Use of webboards for distance learning: a physical therapy model.
AB  - In today's world of ever-increasing knowledge and technology, mastering the use
      of information is critical for success. U.S. Army physical therapists have
      successfully used the Knowledge Management Network as a tool to foster
      communication, education, and training. The model outlined in this article can
      serve both as a model for promoting distance learning and as a success story of
      how to merge today's technology with the medical community to improve
      productivity and communication.

PMID- 11315470
TI  - Military graduate medical education in internal medicine: an outcomes study.
AB  - Military graduate medical education has come under increasing scrutiny in recent
      years as the size of the military medical force declines. To document the
      outcomes of military graduate medical education in internal medicine, a cohort of
      Air Force internal medicine residency graduates from Wright-Patterson Medical
      Center were studied and their residency performance, staff performance, and
      active duty retention recorded. The study cohort had an outstanding residency
      performance, as measured by research experience and board certification rate.
      They also performed well as military staff physicians, receiving numerous
      individual military medals while holding important administrative and supervisory
      positions in the military. Finally, the study cohort had a higher than expected
      active duty retention rate. These findings support the notion that military
      graduate medical education in internal medicine produces outstanding military
      internists.

PMID- 11315471
TI  - The effects of region-specific resistance and aerobic exercises on bone mineral
      density in premenopausal women.
AB  - Epidemiological, cross-sectional, and prospective studies strongly suggest that
      exercise has beneficial effects on bone mass in premenopausal women. We
      prospectively compared the effects of resistance or aerobic exercises on regional
      bone mass in premenopausal active duty military women ranging in age from 19 to
      40 years. Subjects were assigned, by preference, to a resistance exercise group
      or an aerobic exercise group and instructed to exercise at least 30 minutes per
      day, three times per week, for a period of 1 year. Bone mineral density (BMD) was
      measured by dual photon absorptiometry at the lumbar spine and femoral neck and
      by single photon absorptiometry at the mid radius at baseline, 6 months, and 12
      months. BMD increments during the study were statistically significant at all
      sites in both exercise groups. Comparisons between the groups showed that after
      12 months, BMD increased similarly in the lumbar spine (2.2% resistance vs. 1.8%
      aerobics, p = not significant) but more in the resistance group in the femoral
      neck (5.0% vs. 2.7%, p < 0.001) and the mid radius (7.8% vs. 6.7%, p < 0.05).
      Both resistance and aerobic exercises increase regional bone mass, particularly
      cortical bone mass, in premenopausal women. Resistance work appears to have a
      slightly greater effect on cortical bone than aerobics alone. A combination of
      aerobics and resistance exercises, therefore, may be a useful strategy for
      increasing peak bone mass in premenopausal women.

PMID- 11315472
TI  - A comparison of the effects of sarin and succinylcholine on respiratory
      parameters in anesthetized domestic swine.
AB  - Differences in the "respiratory paralysis" caused by sarin (GB) and
      succinylcholine (SDC) were observed in a domestic swine model using a bedside
      pulmonary dynamics monitor. GB was administered intravenously (9 micrograms/kg/30
      min) and compared with SDC administered intravenously (20 mg/30 min). All animals
      developed respiratory insufficiency indicated by decreased respiratory frequency.
      Minute ventilation was relatively maintained in animals that received GB by
      increasing tidal volume, whereas both of these parameters decreased in animals
      that received SDC. GB animals showed an increase in airway resistance and work of
      breathing. The former was unchanged and the latter was decreased in animals that
      received SDC. Mouth occlusion pressure at 100 milliseconds and tidal volume were
      relatively maintained in GB animals but decreased in SDC animals, suggesting a
      central mechanism for respiratory paralysis with GB and a peripheral mechanism
      for respiratory paralysis with SDC.

PMID- 11315473
TI  - Availability of smoking cessation resources for U.S. Army general medical
      officers.
AB  - Adequate resources are a necessity in providing effective smoking cessation
      interventions to active duty soldiers. The availability of smoking cessation
      resources was measured by a survey of Army general medical officers (GMOs).
      Questionnaires were successfully mailed to 232 Army GMOs, which was the entire
      population of this group in 1997. One hundred fifty GMOs (65%) returned the
      questionnaire voluntarily and anonymously. Fifty-three percent of GMOs identified
      the nicotine patch as a formulary item. All responders indicated that some form
      of nicotine replacement was available on formulary or for purchase in the area.
      Eighty-two percent of GMOs reported that group smoking cessation programs were
      available. The widespread availability of group smoking cessation programs may
      reflect an emphasis on this strategy by the Army's health promotion program.
      Additional attention needs to address the availability of nicotine replacement
      items and other adjunctive medications without cost to the beneficiary at
      military installations.

PMID- 11315474
TI  - War head injury score: an outcome prediction model in War casualties with acute
      penetrating head injury.
AB  - OBJECTIVE: To evaluate in war casualties with acute penetrating head injury
      whether the summed War Head Injury Score (WHIS) is a better predictor of
      mortality than either the Glasgow Coma Scale (GCS) score or the Injury Severity
      Score (ISS) alone and to establish its specific applicability. METHODS:
      Sensitivity, specificity, correct outcome prediction, and discrimination were
      assessed in 43 patients in the war group (ballistic injuries) and 41 patients in
      the civil group (nonballistic injuries) during the period 1991 to 1995. The new
      model was generated using the sum of GCS scores and ISS, to which a coded value
      was applied for summation. RESULTS: In the war group, the mortality rate was 23%;
      the sensitivity and specificity of WHIS were 100% and 79%, the sensitivity and
      specificity of GCS score were 90% and 85%, and the sensitivity and specificity of
      ISS were 100% and 49%, respectively. In the civil group, the mortality rate was
      39%; the sensitivity and specificity of WHIS were 87% and 76%, the sensitivity
      and specificity of GCS score were 63% and 90%, and the sensitivity and
      specificity of ISS were 100% and 56%, respectively. CONCLUSION: With regard to
      civilians, war casualties with acute penetrating head injury more often have
      multiple injuries. WHIS represents a new scoring system that incorporates both
      GCS score and ISS.

PMID- 11315475
TI  - Physical medicine and rehabilitation in the military: the Bosnian mass casualty
      experience.
AB  - On February 5, 1994, a 120-mm mortar shell crashed into the main Market Square of
      Sarajevo, Bosnia. The explosion killed 66 and injured 206. The United States
      evacuated 71 of the injured to Landstuhl Regional Medical Center, where the
      Physical Medicine and Rehabilitation Service evaluated 28 victims. This mass
      casualty evacuation underscores the role of Army physiatrists in humanitarian
      assistance and wartime casualty management. The author collected data regarding
      demographic factors, injury types, complications, and functional limitations.
      Seventeen of the 28 patients evaluated were injured during the market bombing,
      with the rest being injured before the bombing. Of 132 diagnoses in these 28
      patients, 31 were fractures, 14 were amputations, 8 were peripheral neuropathies,
      3 were spinal cord injuries, and 1 was a traumatic brain injury. Contractures and
      decubitus ulcers, both complications of immobility, accounted for 18 of the
      diagnoses. Ambulatory impairments were present in all of the patients, and 4
      patients had major impairments in activities of daily living.

PMID- 11315476
TI  - Detection of interproximal caries using methods applicable to a field
      environment: digital radiography, manually processed film, and self-developing
      film.
AB  - The purpose of this study was to determine if the alternatives to conventional
      dental radiography are diagnostically equivalent to conventional film in a field
      setting. These alternatives, digital radiography and self-developing film, could
      significantly decrease the weight and cubic size of a field X-ray set. Five
      radiographic methods were evaluated: self-developing film, manually processed
      film, film developed in an automatic processor, digital images on a liquid
      crystal diode, and digital images on a cathode ray tube screen. The results
      indicate that the liquid crystal diode system adversely affected the ability of
      the dentist to detect small interproximal lesions. The other methods were
      statistically equivalent. A recommendation for an "image acquisition" system to
      be included in a field dental treatment facility should be based on clinical
      factors as well as nonclinical factors such as cost, reliability, and logistical
      support requirements.

PMID- 11315477
TI  - Patient service attitudes among newly commissioned providers and administrators.

PMID- 11315478
TI  - Going the distance: how far will women travel to undergo free mammography?
AB  - This study examined the effect of travel distance on mammography facility choice,
      with mammography cost held constant. Women who were eligible to undergo free
      mammography at a military treatment facility (MTF) responded to a mail survey by
      indicating whether their last mammograms were performed at an MTF (for free) or
      at a civilian medical facility (for a fee). The distance from each respondent's
      home to the MTF was also recorded. Analyses indicated that a majority of the
      women who traveled to the MTF for a mammogram lived within 20 miles of the
      facility. Results of this study suggest that, even if mammography screening is
      offered free of charge, women may not use the service if they must travel more
      than 20 miles to receive it. Furthermore, any MTF trying to increase its TRI-CARE
      market share may want to focus its marketing efforts on individuals who live
      within a 20-mile radius.

PMID- 11315479
TI  - A computerized medical incident reporting system for errors in the intensive care
      unit: initial evaluation of interrater agreement.
AB  - Errors resulting in adverse events in the medical care system are ubiquitous and
      underreported. Critical incident techniques that have been used to reduce errors
      in aviation have recently been applied to evaluate adverse events in the critical
      care arena. We report an evaluation of interrater agreement on responses to
      questions concerning adverse event reporting using a computer-based medical
      incident reporting system (MIRS). Thirty-four intensive care unit staff
      volunteers reviewed five fabricated test cases containing iatrogenic factors,
      then completed an incident report for each case using the MIRS. Interrater
      agreement was significant for all five cases (p < 0.01). The time required to
      complete a report decreased significantly from the first case to the last (p <
      0.01). Overall, the MIRS was perceived as a relatively quick (< 6 minutes) and
      comprehensive reporting tool. The results indicate that health care providers
      report adverse events similarly, suggesting that the MIRS would be a useful tool
      in the reduction of errors (as a process improvement program) and to facilitate
      the continuing process of health care improvement.

PMID- 11315480
TI  - Bezold's abscess.

PMID- 11315481
TI  - The fitness training unit in U.S. Army basic combat training: physical fitness,
      training outcomes, and injuries.
AB  - This study involved a retrospective examination of physical fitness, training
      outcomes, and injury rates among personnel in the Fitness Training Unit (FTU).
      Personnel were assigned to the FTU based on low performance on push-ups, sit-ups,
      and/or a 1-mile run (N = 44 men, 95 women) and received an augmented physical
      fitness program before basic combat training (BCT). They were compared with 712
      men and 379 women who took the same test but were not assigned to the FTU and
      went directly to BCT. FTU and non-FTU personnel trained in the same battalions.
      Army Physical Fitness Test scores and BCT outcomes (discharged or completed BCT
      in 8 weeks) were obtained from unit training records. Injuries during BCT were
      documented from a review of the medical records. On entry to BCT, FTU women had
      similar 2-mile run times compared with non-FTU women (21.6 vs. 21.5 minutes,
      respectively; p = 0.86); FTU men were considerably slower on the 2-mile run than
      non-FTU men (20.3 vs. 17.3 minutes; p < 0.01). FTU women and non-FTU women had
      similar graduation success (60% vs. 68%, respectively; p = 0.14) and time-loss
      injury rates (1.3 vs. 1.4 people injured/100 person-days, respectively; p =
      0.90). FTU men were less likely to graduate than non-FTU men (55% vs. 82%; p <
      0.01) and more likely to suffer a time-loss injury (1.2 vs. 0.7 people
      injured/100 person-days; p < 0.01). Efforts should be directed toward providing a
      sufficient training stimulus to improve the aerobic fitness level of men (as well
      as women) in the FTU.

PMID- 11315482
TI  - Trauma-induced coagulopathy and treatment in Kosovo.
AB  - The 67th Combat Support Hospital at Camp Bondsteel, Kosovo, treated victims of
      trauma on an almost daily basis at the beginning of U.S. peacekeeping efforts in
      the region. Military health care personnel must respond quickly and efficiently
      when confronted with patient wounds resulting in massive blood losses. The
      limited medical resources of a field hospital often complicate efforts to treat
      the most severe injuries. One such case involved a young farmer riddled with
      gunshot wounds. Early volume/blood resuscitation before, during, and after
      surgery led to a massive blood coagulopathy. This case study describes the
      actions the physicians and nurses initiated to save this victim of violence. The
      subsequent discussion delineates methods to reduce intraoperative blood losses,
      blood transfusion alternatives, and technological advances in trauma
      resuscitation.

PMID- 11315483
TI  - Chronic exertional compartment syndrome after minor injury to the lower
      extremity.
AB  - Since the 1950s, chronic exertional compartment syndrome of the lower leg has
      been thoroughly reported in the literature. The predisposing factors and
      pathophysiology of this condition, however, still are not fully understood. We
      present a case of a well-conditioned individual who developed a chronic
      exertional compartment syndrome of the left lower leg anterior compartment after
      a direct blow injury during a softball game. Trauma is not routinely implicated
      as a risk factor for chronic compartment syndrome, and the literature on this
      topic is scarce. We suggest that trauma, even low-velocity trauma, may
      precipitate a chronic exertional compartment syndrome. We review the literature
      regarding chronic exertional compartment syndromes preceded by trauma and offer
      explanations regarding the mechanisms by which a traumatic event may induce a
      chronic compartment syndrome.

PMID- 11315484
TI  - [New platelet inhibitors. More drugs, more problems].

PMID- 11315485
TI  - [New platelet inhibitors].
AB  - The antiplatelet action of acetylsalicylic acid is mostly used in vascular
      medicine. In the meantime two other classes of platelet inhibiting agents have
      been introduced. Thieopyridines (Ticlyridin, Clopidogrel) have been shown to
      inhibit ADP induced platelet aggregation with persistence of this effect for
      several days after withdrawal. The short acting intravenous Glycoprotein IIb/IIIa
      inhibitors considerably improved the management of acute coronacy syndrome. The
      above mentioned compounds may be applied in combination at least for some days,
      and heparins are given in addition. Mainly the bleeding complications are to be
      taken into account especially if patients have to undergo emergency
      interventions. Hemodialysis or platelet concentrates are recommended to
      antagonise the antiplatelet effects immediately.

PMID- 11315486
TI  - [The NACA scale. Construct and predictive validity of the NACA scale for
      prehospital severity rating in trauma patients].
AB  - The NACA-scale is used in many Austrian, German and Swiss emergency medical
      systems for demographic description of emergency patients. Little attention has
      been payed to the evaluation of its construct and predictive validity. In 427
      consecutive trauma patients rescued in primary mission the NACA-Scale and the
      Injury Severity Score (ISS) were determined. Outcome data were obtained from
      medical charts and by written or telephone requests. Data were analysed with
      Spearman-Rank-Correlation. NACA-Grade and ISS-values showed only a moderate
      correlation with a considerably large spread (Rho = 0.721). Both severity scores
      demonstrated a good correlation to mortality (Rho = 0.976/0.994) and to transfer
      to an ICU (Rho = 0.964/0.943), as well a moderate correlation to the duration of
      ICU-stay (Rho = 0.722/0.756) and of hospital stay (Rho = 0.558/0.694). The NACA
      scale adequately describes life threat in trauma victims and correlates well with
      morbidity and mortality. Thus, it is a valuable tool for demographic purposes in
      emergency medical systems. For more precise prehospital severity rating in trauma
      patients, the NACA-scale should be supplemented or replaced by a physiologically
      based prehospital severity score.

PMID- 11315487
TI  - [Low alkali-hydroxide content in soda limes does not lead to reduction of
      compound A formation from sevoflurane during low-flow anesthesia].
AB  - The alkali hydroxide content in soda lime induces Compound A formation from
      Sevoflurane (Sevo). This study was designed to answer the question if the use of
      potassium hydroxide-free Soda Lime (SL) would lead to lower Compound A levels as
      compared to Sodasorb (SO). A total of 30 patients scheduled for elective
      laparoscopic cholecystectomy received Sevo anaesthesia under low-flow conditions
      (0.8 l/min fresh gas flow). Each absorbent was used in 15 patients, but 3
      patients of the SO group were excluded due to technical problems with Compound A
      analysis. Hemodynamic parameters, parameters of ventilation and gas
      concentrations were documented. Compound A concentrations were measured by gas
      chromatography from gas samples before Sevo application and 20, 40, 60, 90 and
      120 min after low-flow start. Mean endtidal Sevo concentrations were 1.94 +/-
      0.17 (SO) and 1.97 +/- 0.15 (SL) vol %, the total anaesthetic exposition was 1.52
      +/- 0.36 (SO) and 1.64 +/- 0.47 (SL) MAC-h (n.s). The maximum Compound A
      concentration was significantly higher in SL group (19.6 +/- 2.8 vs. 11.7 +/- 4.1
      ppm, p < 0.001). Therefore, elimination of potassium hydroxide from carbon
      dioxide absorbents alone did not lead to a reduction of Compound A formation
      during low-flow anaesthesia.

PMID- 11315488
TI  - [Laparoscopic cholecystectomy in a patient with honeycomb lung].
AB  - Laparoscopic surgery of the gallbladder has increasingly replaced open techniques
      due to postoperative benefits (less pulmonary complications, less postoperative
      pain, earlier mobilisation). Specific intraoperative effects of pneumoperitoneum
      have led to some uncertainty if cardiac and/or pulmonary high-risk cases should
      be done laparoscopically. We describe anaesthesiological management of a 72 year
      old patient with a unilateral leftsided honeycomb lung (two very large cysts) to
      undergo laparoscopic cholecystectomy. Vital capacity was reduced to 45%, forced
      expiratory 1 second volume to 41%, preoperative bloodgas analysis revealed a paO2
      of 64 mmHg and a paCO2 of 40 mmHg. Under spontaneous breathing the patient was
      fiberoptically intubated with a left sided double lumen tube (Mallinckrodt,
      Athlone/Irland; 37 Ch) using balanced anaesthesia. The healthy right lung was
      hand ventilated with 100% oxygen to avoid excessive airway pressures (peak airway
      pressure 27 mbar, mean airway pressure 22-24 mbar). The diseased left lung was
      passively insufflated with oxygen. The intraabdominal pressure was limited to 10
      mmHg. Muscle relaxation was achieved with atracurium under monitoring using a
      nerve stimulator. The paCO2 increased from 40 to 57 mmHg during the operation,
      but returned to normal immediately postoperatively. All other ventilatory and
      hemodynamic parameters were uneventful during the 35 minute procedure. The
      patient was extubated at the end of the procedure and monitored on the intensive
      care ward for one night. A postoperative chest X-ray revealed a mediastinal shift
      of 2 cm to the right, healthy side as well as an atelectasis on this side. The
      shift was most likely due to hypoventilation of the right lung, with the ensuing
      atelectasis drawing the mediastinum to the right. Under physiotherapy this shift
      had resolved by the next morning. The patient could be discharged from hospital
      on day seven and fully recovered. Especially the severely cardiopulmonary
      compromised patient benefits from a laparoscopic procedure, due to less
      postoperative reduction of pulmonary function. Careful and individually adapted
      monitoring and anaesthetic techniques are necessary to successfully counteract
      the special implications of pnemoperitoneum.

PMID- 11315489
TI  - [Tracheal rupture: delayed diagnosis with endobronchial intubation].
AB  - Tracheobroncheal rupture is a rare complication of intubation techniques using a
      stylet. In this case report the patient was intubated by an emergency physician
      in a preclinical setting after a motor vehicle accident. Iatrogenic tracheal
      laceration was masked by inappropriate position of the endobronchial tube. By
      chance ventilation was maintained to both lungs by flow through the Murphy's eye
      of the tube and the lumen of the tube. In correcting the deep tube position after
      a chest x-ray laceration of the trachea was unmasked and ventilation problems
      occurred immediately. The tube was replaced under fiberoptical control and the
      patient was managed for surgical repair using a jet ventilation technique. In
      this case two complications of endobronchial intubation occurred, but the deep
      tube placement opposed the effects of the tracheal laceration. This was probably
      life saving for the patient during emergency transfer by helicopter after the
      accident. The anaesthesiological management during tracheal repair is discussed.

PMID- 11315490
TI  - [Automatic tube compensation (ATC)].
AB  - The endotracheal tube (ETT) is a considerably flow-dependent and, therefore,
      variable mechanical load. Conventional modes of respiratory support cannot
      adequately compensate for the tube resistance in inspiratorion and not at all in
      expiration. Automatic tube compensation (ATC) compensates for the flow-dependent
      pressure drop across the tracheal tube by a positive pressure support in
      inspiration and by a negative pressure support in expiration. The pressure
      support closely follows the nonlinear pressure-flow curve of the ETT. Automatic
      tube compensation has an indirect closed-loop working principle since the target
      tracheal pressure is not directly measured but rather calculated from
      continuously measured airway pressure and flow rate. It is not an own ventilatory
      mode but rather a component of flow-proportional pressure support which can be
      combined with all conventional ventilatory modes, and provides a rational basis
      for subdividing the pressure support to overcome the mechanical load of the
      tubing and to overcome that of the respiratory system. Partial tube obstructions,
      which could decrease the effectivity of ATC, could be detected automatically by
      analysing the expiratory flow signal using a software, which could be easily
      implemented into the ventilator. The effectivity of ATC during long-term
      application can be maintained by intermittent short-term measurement of the
      tracheal pressure. Up to now there is no commercially available ventilator which
      allows complete expiratory ATC. Studies in volunteers and in mechanically
      ventilated patients have convincingly shown that ATC reduces work of breathing
      and increases respiratory comfort. In addition, successful extubation could be
      better predicted with this mode in difficult-to-wean patients compared to other
      modes. There are no special rules in the clinical application of ATC. However, to
      prevent overassist the support level of the ventilatory mode which is combined
      with ATC should be reduced.

PMID- 11315491
TI  - [Electric nerve stimulation in relation to impulse strength. A quantitative study
      of the distance of the electrode point to the nerve].
AB  - In the present study the difference of the distances of the tip of the needle to
      the nerve at similar current intensities but different pulse widths (100
      microseconds vs. 1000 microseconds) were determined by means of 20 blockades of
      the sciatic nerve using the transgluteal approach of Labat. Comparable current
      intensities at different pulse widths (100 microseconds vs. 1000 microseconds)
      were compared in the same way, using the same position of the needle. At a pulse
      width of 100 microseconds and a current intensity of 0.30 mA, the tip of the
      needle is on an average of 5.0 mm closer to the nerve than with a pulse width of
      1000 microseconds and a comparable current intensity of 0.28 mA (difference
      statistically highly significant; p < 0.005). The comparison of the current
      intensities at different pulse widths at the same needle-position shows that the
      difference of the current intensities becomes lower when approaching the nerve.
      At the most distant point measured in this study, a current intensity of 0.94 mA
      at 100 microseconds corresponds to an aquivalent current of 0.30 mA at 1000
      microseconds (difference 0.64 mA); after an approach of 5.0 mm to the sciatic
      nerve, this difference is significantly lower (0.30 mA at 100 microseconds, 0.11
      mA at 1000 microseconds, difference 0.18 mA; p < 0.01). This means that the
      control of peripheral nerve stimulation is superior at a pulse width of 100
      microseconds because a similar distance corresponds to a greater difference of
      the current. The success rate of the blockade was 95% at a current of 0.30 mA at
      100 microseconds. Nerve lesions or other complications have not been seen. In
      conclusion, safe and successful nerve blocks in patients without polyneuropathia
      using the peripheral nerve stimulation seems to be obtained at a current
      intensity of about 0.30 mA at a pulse width of 100 microseconds.

PMID- 11315492
TI  - [Spontaneous versus controlled respiration with the laryngeal mask. A review].
AB  - Over the last 10 years, the Laryngeal Mask Airway (LMA) has gained widespread
      acceptance as a general purpose airway for routine anaesthesia. Published data
      from large studies and reports have confirmed the safety and efficacy of the
      device for spontaneous and controlled ventilation during routine use. The initial
      experience with the LMA should ideally be confined to short cases requiring the
      patient to remain spontaneously ventilating. With experience, it will be found
      that less anesthetic agent is required during anesthesia with the LMA and patient
      recovery should be improved as a result. Spontaneous breathing is the chosen mode
      of ventilation in approximately 60% of LMA uses in the UK. During spontaneous
      breathing a minimal inspiratory pressure support will help with higher endtidal
      carbon dioxide levels. The anaesthetist should be experienced with using the LMA
      in spontaneously ventilating patients before using it with positive pressure
      ventilation. Several large scale studies have failed to show any link between
      positive pressure ventilation and pulmonary aspiration or gastric insufflation.
      The main disadvantage of the LMA is that it does not protect against aspiration.
      From a practical point of view, most fasted patients with normal lung compliance
      may be mechanically ventilated through the LMA to airway pressures of
      approximately 20 cmH2O. The low pressure seal implies that tidal volumes should
      be approximately 6-8 ml*kg-1 and the inspiratory flow rates should be reduced to
      achieve adequate and safe ventilation.

PMID- 11315493
TI  - [Willebrand-Jurgens-Syndrome].

PMID- 11315494
TI  - [Thoracic epidural anesthesia].

PMID- 11315495
TI  - [PEEP].

PMID- 11315496
TI  - [Proxy decision in health questions and advance designations by patients.
      Comments on the paper of von M. Stratling et al. in Der Anaesthesist (2000)
      49:657-674].

PMID- 11315497
TI  - [The decision incompetent patient in the space between deception and medicine. A
      reply to the remarks of K.W. Schmidt and M. Sold].

PMID- 11315498
TI  - [Anesthesia for craniomaxillofacial surgery].

PMID- 11315499
TI  - Effect of randomization of mixtures of butter oil and vegetable oil on absorption
      and lipid metabolism in rats.
AB  - BACKGROUND: The nutritional effect of the regiospecific distribution of fatty
      acids in edible fats is currently discussed due to an increased use of
      interesterification of fats for human consumption. However, disagreeing results
      have been reported which may be due to the varying composition of the dietary
      fats compared. Data on the fate of such lipids beyond the bloodstream is rather
      scarce and animal model studies are needed. AIM OF THE STUDY: To compare the
      metabolism of butter oil and mixtures of butter and rapeseed oil, native or
      randomized, in a rat model. The regiospecific fatty acid distribution present in
      dietary fats was followed through absorption, chylomicron formation, and
      deposition in adipose tissue and in different liver lipids (triacylglycerols,
      phosholipids, and cholesterol esters). METHODS: Rats were fed for 6 weeks from
      weaning either butter oil (BO), a butteroil-rapeseed oil mixture 65:35 w/w (BR)
      or a randomized mixture of BR (tBR). Half of the animals were used for organ
      analysis, the rest for a postprandial study with the same fats and isolation of
      chylomicrons. The regiospecific distribution of the fatty acids present in the
      dietary fats was followed during metabolism by analyses of chylomicrons, depot
      fat and liver lipids, using regiospecific cleavage followed by TLC separation and
      quantification by GC. RESULTS: Randomization of edible fat mixtures leading to
      equal distribution of fatty acids between TG positions is directly reflected in
      the composition of chylomicrons. During clearing by lipoprotein lipase this
      positional distribution is abolished and the regiospecific composition of
      triacylglycerols in adipose tissue is completely identical for BR and tBR.
      Chylomicron remnants, which are taken up by the liver, are correspondingly fully
      degraded to free fatty acids by hepatic lipase, and distribution of fatty acids
      in liver triacylglycerols, phospholipids and cholesterol esters are identical for
      the groups fed either BR or tBR. The group fed BO with a low content of linoleic
      acid is on the borderline of essential fatty acid-deficiency. CONCLUSION:
      Randomization (interesterification) of butter oil with rapeseed oil (65:35 w/w)
      for use as edible fat did not have any impact on the fatty acid composition
      beyond the chylomicron step when compared to the native mixture.

PMID- 11315500
TI  - Vitamin E reduces lipid peroxidation in experimental hepatotoxicity in rats.
AB  - BACKGROUND AND AIMS: Lipid peroxidation is believed to be involved in the
      pathophysiology of a number of diseases and in the process of aging. This study
      investigates the effects of dietary supplementation with vitamin E (20 g/kg diet
      of all-rac-alpha-tocopheryl succinate for 3 weeks) on both non-enzymatic and
      enzymatic lipid peroxidation in experimental rats with carbon tetrachloride
      (CCl4)-induced hepatotoxicity (2.5 mL/kg body). METHODS: Plasma, urine and liver
      samples from control rats (n = 6), CCl4-treated rats (n = 6), and rats
      supplemented with vitamin E prior to CCl4 treatment (n = 8) were collected. Non
      enzymatic lipid peroxidation induced by free radicals was investigated by
      measurement of a major F2-iso-prostane, 8-iso-prostaglandin F2 alpha (8-iso-PGF2
      alpha). Cyclooxygenase-catalyzed enzymatic lipid peroxidation was measured with a
      major PGF2 alpha metabolite, 15-keto-13,14-dihydro-prostaglandin F2 alpha (15-K
      DH-PGF2 alpha). Malondialdehyde and antioxidants in plasma were also quantified.
      RESULTS: CCl4 treatment alone resulted in significantly higher levels of plasma,
      urinary and liver 8-iso-PGF2 alpha, and of plasma and urinary 15-K-DH-PGF2 alpha
      compared to controls. Rats supplemented with vitamin E prior to CCl4 treatment
      had significantly lower levels of urinary and liver 8-iso-PGF2 alpha, urinary 15
      K-DH-PGF2 alpha, and plasma malondialdehyde than rats treated with CCl4 alone.
      However, plasma 8-iso-PGF2 alpha and plasma 15-K-DH-PGF2 alpha were not affected
      by vitamin E supplementation. CONCLUSION: Thus, both non-enzymatic and enzymatic
      lipid peroxidation during experimental hepatic oxidative injury were suppressed
      by dietary vitamin E supplementation in rats.

PMID- 11315501
TI  - Dietary oleoyl-estrone delays the growth rate of young rats.
AB  - BACKGROUND: Oleoyl-estrone administration induces the rapid loss of fat
      preserving body protein. AIM OF THE STUDY: We intended to check whether the fat
      shedding effect of oleoyl-estrone arrests growth in young rats, limiting the
      buildup of protein and fat. METHODS: Oleoyl-estrone diluted in a powdered
      hyperlipidic diet (33 mumol/kg) was given for 30 days to 30-day old Zucker lean
      (Fa/?) rats. Their body weight and food consumption were followed daily; on day
      30 of treatment (60-day old rats), whole body composition (lipid, protein) was
      determined, and plasma energy parameters and leptin were measured. RESULTS:
      Oleoyl-estrone-treated rats grew more slowly than controls fed the hyperlipidic
      diet alone, and on day 60 their lipid content was about half that of controls.
      Protein content per kg was identical in both groups, but treated rats tended to
      accumulate less nitrogen and energy because of their smaller size. No changes in
      plasma glucose, urea, triacylglycerols or total cholesterol were observed, but
      oleoyl-estrone-treated rats showed lower circulating leptin than controls.
      CONCLUSION: Despite limiting the accumulation of lipids, oleoyl-estrone slowed,
      but did not arrest growth of young rats, nor elicit a loss of fat or protein.

PMID- 11315502
TI  - Estimation of available energy of dietary fibres by indirect calorimetry in rats.
AB  - BACKGROUND: Knowledge of energetic availability of dietary fibres is important
      for human nutrition. But up to now results are often different and depend on the
      methods used. Estimation of metabolisable energy of dietary fibres (mainly by
      balance technique) is a time-consuming procedure and needs special technical
      effort. AIM OF THE STUDY: Validation of the experimental design for short-term
      studies by using indirect calorimetry with feeding below maintenance requirement
      to evaluate the energetic availability of dietary fibres and their influence on
      absorption velocity of carbohydrates (CHO). METHODS: Energy expenditure and CHO
      oxidation (including short-chain fatty acids as fermentation products) were
      estimated in Wistar rats over 23 h after being fed a basal diet for the first day
      (300 KJ/kg0.75, 20% protein, 3% fat, 77% CHO) followed by supplementation with
      either microcrystalline cellulose, the soluble rye fibre arabinoxylan, apple
      pectin, amylomaize starch (with 48% of resistant starch) or gelatinised wheat
      starch (200 KJ/kg0.75 each) as control for the following days. Energetic
      availability was determined by comparing the increase of CHO oxidation after
      addition of gelatinised wheat starch with that of the dietary fibres tested.
      RESULTS: In comparison to wheat starch (100%), the following energetic
      availability of the dietary fibres was found: microcrystalline cellulose 14%,
      arabinoxylan 33%, pectin 39%, amylomaize starch 62%. The time-course of CHO
      oxidation indicated that microcrystalline cellulose enhances, whereas the soluble
      rye fibre slows down the velocity of CHO absorption due to the different
      consistency of the intestinal contents modified by the kind and properties of the
      used dietary fibres. After intake of arabinoxylan or pectin, CHO oxidation
      remained at a higher level during the experimental period elucidating an
      increased activity of fermentation to short-chain fatty acids. CONCLUSIONS: Short
      term experiments in rats using indirect calorimetry are a suitable method for
      comparative estimation of the energetic availability of dietary fibres. Results
      are partly in agreement with values estimated by long-term in vivo methods.

PMID- 11315503
TI  - Red palm oil in the maternal diet increases provitamin A carotenoids in
      breastmilk and serum of the mother-infant dyad.
AB  - BACKGROUND: Despite vitamin A supplementation programs, vitamin A deficiency in
      children remains a public health concern in Honduras. AIM OF THE STUDY: We
      investigated the effectiveness of short-term dietary supplementation of mothers
      with red palm oil as a strategy for improving the vitamin A status of the mother
      infant dyad. METHODS: Lactating mothers in Colonia Los Pinos, a barrio of
      Tegucigalpa, Honduras, consumed a total of 90-mg beta-carotene as red palm oil (n
      = 32) supplements (n = 36) or placebo (n = 18) in six equal doses over 10 days.
      Carotenoids and retinol in maternal and infant serum, and breastmilk carotenoids
      and retinol were measured before and after supplementation. Maternal diet was
      evaluated by 24-hour recall. RESULTS: Maternal serum alpha-carotene and beta
      carotene concentrations were increased 2 fold by palm oil compared with 1.2 fold
      by beta-carotene supplements. Changes were significantly different in infant
      serum alpha-carotene but not beta-carotene among the three experimental groups.
      Increases in breastmilk beta-carotene were greater for the palm oil group (2.5
      fold) than for the beta-carotene supplement group (1.6 fold) and increases in
      milk alpha-carotene concentrations (3.2 fold) were slightly greater than those of
      beta-carotene. There were also small but significant changes among groups in
      breastmilk lutein and lycopene. Breastmilk retinol was not significantly
      different among the groups over the treatment period. CONCLUSIONS: Red palm oil
      in the maternal diet increases provitamin A carotenoids in breastmilk and serum
      of the mother-infant dyad. The use of dietary red palm oil to improve the vitamin
      A status of this population should be further investigated.

PMID- 11315504
TI  - Contrasting effects of acute and chronic dietary exposure to 2-amino-3-methyl
      imidazo[4,5-f]quinoline (IQ) on xenobiotic metabolising enzymes in the male
      Fischer 344 rat: implications for chemoprevention studies.
AB  - BACKGROUND: 2-Amino-3-methyl-imidazo[4,5-f]quinoline (IQ) is a mutagen produced
      in cooked food. It is commonly present in the human diet and often used as a
      (pro)carcinogen for chemoprevention studies. Many foodstuffs act as
      chemopreventers by altering xenobiotic metabolising enzyme expression in favour
      of detoxication over bioactivation pathways. However, IQ itself can also affect
      enzyme expression, which may be a confounding factor in chemoprevention studies.
      AIM OF STUDY: Chronic low dose IQ exposure is intuitively closest to the human
      dietary situation. The aim was to investigate the effects of chronic dietary
      exposure to IQ on the expression of enzymes involved in the bioactivation and
      detoxification of xenobiotics and to compare this with acute exposure, often used
      in chemoprevention studies. METHODS: Male Fischer rats received IQ (300 ppm) in
      the diet (AIN-76) for 52 weeks or were given IQ (20 mg.kg-1) orally for 3 days.
      Animals were killed, livers removed and subcellular fractions prepared. A range
      of enzymes was selected to allow investigation of several cellular mechanisms.
      Enzyme expression and activity were determined by Western blotting and the use of
      selective probe substrates as appropriate. RESULTS: Chronic exposure to IQ led to
      an increase in phase II detoxifying enzymes. Both the activity and expression of
      glutathione S-transferase (GST-A1/2) were increased, as were NADPH: Quinone
      oxidoreductase (NQO), UDP-glucuronosyl transferase (UGT) and beta-glucuronidase
      activities. There were no statistically significant changes in the potential for
      bioactivation by three cytochrome P450s. In contrast, acute IQ exposure
      significantly increased the expression and activity of some cytochrome P450
      (CYP1A1 and CYP1A2), UGT and beta-glucuronidase, but significantly decreased
      glutathione S-transferase expression and activity. There was a non-significant
      decrease in NQO but no change in CYP3A2 and CYP2E1 activities. CONCLUSIONS: The
      changes after acute exposure suggest an interaction through the Ah receptor and
      xenobiotic response element, modified by the glucocorticoid response element. In
      contrast, the pattern of effects after chronic exposure suggests activation of
      the antioxidant response element (ARE). Although the acute model is more
      practically convenient for short-term chemoprevention screening, the data suggest
      that an entirely new mechanism is being invoked that completely masks effects of
      the ARE that occur during chronic exposure. There is a danger that
      chemopreventive strategies developed using acute models may be misleading, since
      the mechanism is unlikely to occur during human dietary exposures.

PMID- 11315505
TI  - Monocyte-chemoattractant-protein-1-mediated migration of human monocytes towards
      blasts from patients with acute myeloid leukemia.
AB  - PURPOSE: In the present study the possible clinical relevance of monocyte
      chemoattractant protein (MCP)-1 in patients with acute myeloid leukemia (AML) was
      established. METHODS: The pattern of migration of human monocytes towards the
      supernatants of blasts from 15 patients with AML was studied and the role of MCP
      1, produced by these blasts, was assessed. RESULTS: In 4 patients (group 1) the
      amount of monocyte migration was low and not inhibited by the addition of anti
      hMCP-1. In 11 patients, the amount of monocyte migration was high; after addition
      of anti-hMCP-1, monocyte migration was either completely (8 patients, group 2),
      or partly or not (3 patients, group 3) inhibited to the level of chemokinesis. In
      groups 1 and 2, there was a good correlation (r = 0.67) between the concentration
      of MCP-1 in the supernatants and the amount of monocyte migration. In group 3,
      such a correlation was not evident, suggesting that another chemokine might be
      involved or MCP-1 function was impaired by an unknown substance. Finally,
      measurements of MCP-1 during culture of AML blasts showed that the time at which
      maximal amounts of MCP-1 are produced differs between the AML samples.
      CONCLUSIONS: AML blasts produce different amounts of MCP-1, which plays an
      important role in monocyte migration towards most AML blasts. Therefore, in the
      context of adoptive immunotherapy, MCP-1 might be involved in future tumor
      vaccination programmes using autologous MCP-1-transfected irradiated AML blasts.

PMID- 11315506
TI  - Effect of interferon-gamma on the susceptibility to Fas (CD95/APO-1)-mediated
      cell death in human hepatoma cells.
AB  - Many tumors, including hepatocellular carcinomas (HCCs), resist Fas-mediated cell
      death, which is one of the effector mechanisms in the host's anti-tumor response;
      however, this resistance can be abolished by interferon-gamma (IFN-gamma). IFN
      gamma may sensitize Fas-mediated cell death in several ways, but the exact
      mechanism in HCCs is uncertain. In this study, we thoroughly investigated the
      effect of IFN-gamma on the susceptibility of one human normal liver cell line and
      12 HCC cell lines to Fas-mediated cell death. We also investigated the effect of
      IFN-gamma on the expression of various apoptosis-related genes such as the
      Fas/TNF-related genes, the bcl-2 family, and the caspase family of genes.
      Although most cell lines showed considerable constitutive expression of Fas, all
      tested cell lines resisted Fas-mediated cell death without IFN-gamma. When cells
      were pretreated with IFN-gamma, only three cell lines were made significantly
      susceptible to Fas-mediated cell death (SNU-354, SNU-387 and SNU-423); the other
      10 cell lines were not affected. IFN-gamma increased the mRNA expression of Fas,
      TRAIL and caspase-1, and surface Fas was also increased. The strongly sensitized
      cell lines (SNU-354, SNU-387 and SNU-423) showed a particularly potent increment
      in surface Fas after IFN-gamma treatment (increase in surface Fas > 1.7-fold).
      This result enabled us to conclude that a potent increment of surface Fas
      expression is a major sensitizing mechanism of IFN-gamma. We conclude that IFN
      gamma cannot play a sensitizing role in most HCC cell lines and that IFN-gamma
      makes HCC cells susceptible to Fas-mediated cell death through a marked up
      regulation of surface Fas in some HCC cells.

PMID- 11315507
TI  - A listing of human tumor antigens recognized by T cells.

PMID- 11315508
TI  - Dendritic-cell-peptide immunization provides immunoprotection against bcr-abl
      positive leukemia in mice.
AB  - Chronic myelogenous leukemia (CML) is a clonal disorder characterized by
      proliferation of cells that possess the bcr-abl fusion gene resulting in the
      production of one of two possible chimeric 210-kDa tyrosine kinase proteins.
      Since these chimeric proteins are expressed only in leukemic cells they have the
      potential to serve as tumor-specific antigens for cytotoxic T lymphocytes (CTL).
      Using the 12B1 murine leukemia cell line, derived by retroviral transformation of
      BALB/c bone marrow cells with the bcr-abl (b3a2) fusion gene, we have
      demonstrated that intravenous inoculation of 12B1 cells into BALB/c mice results
      in a disseminated acute leukemia analogous to human CML in blast crisis.
      Histological sections of liver and spleen and polymerase chain reaction analysis
      of peripheral blood, bone marrow, liver, spleen and lymph nodes confirmed the
      presence of bcr-abl+ leukemia cells in these murine tissues, while Western blot
      data demonstrated the expression of the fusion protein in 12B1 cells.
      Immunization of mice with dendritic cells (DC) loaded with the synthetic bcr-abl
      chimeric nonapeptide, GFKQSSKAL, led to a 150 times higher frequency of bcr-abl
      specific CTL precursors in the spleen than in mice immunized with peptide alone.
      In vitro re-stimulation of DC-peptide-primed splenocytes resulted in substantial
      secretion of interferon gamma and augmented cytolytic activity against 12B1
      targets. Finally, vaccination with peptide-loaded DC significantly prolonged
      survival of BALB/c mice that were challenged with 12B1 leukemia. The capacity to
      generate bcr-abl-specific CTL in vivo by DC-based immunization may have clinical
      implications in the treatment of CML.

PMID- 11315509
TI  - The growth-regulatory role of B-cell-specific activator protein in NZB malignant
      B-1 cells.
AB  - The transcription factor B-cell-specific activator protein (BSAP) plays an
      important role in B-cell development. We explored the involvement of BSAP in the
      growth regulation of malignant B-1 cells derived from the NZB murine model of
      human chronic lymphocytic leukemia. BSAP protein was found in normal B-2 cells,
      elevated in normal B-1 cells, and highest in NZB malignant B-1 cells. When these
      malignant B-1 cells were treated with antisense oligonucleotides for BSAP, their
      growth was inhibited with a G2/M phase arrest. In contrast, B cell lines that did
      not appear to be of B-1 origin (IgG+/B220+/BSAPlow) were unaffected by treatment
      with antisense BSAP oligonucleotides. Centrifugal elutriation experiments showed
      that BSAP mRNA was expressed at the highest levels in the G2/M phases in
      malignant B-1 cells. Treatment with demecolcine (Colcemid), a known mitotic
      blocker, resulted in a decrease in the level of BSAP gene expression in malignant
      B-1 cells, further demonstrating links between BSAP expression and successful
      G2/M transition in the cell cycle. These data suggest a correlation between BSAP
      and the development of B-1 malignancy, perhaps through the regulation of cell
      cycle progression.

PMID- 11315510
TI  - In vitro characterisation of a monovalent and bivalent form of a fully human anti
      Ep-CAM phage antibody.
AB  - Antibodies to tumour-associated antigens are increasingly being used as targeting
      vehicles for the visualisation and for therapy of human solid tumours. The
      epithelial cell adhesion molecule (Ep-CAM) is an antigen that is overexpressed on
      a variety of human solid tumours and constitutes an attractive target for
      immunotargeting. We set out to obtain fully human antibodies to this antigen by
      selecting from a large antibody repertoire displayed on bacteriophages. Two
      single-chain variable antibody fragments (scFv) were identified that specifically
      bound recombinant antigen in vitro. One of the selected antibodies (VEL-1) cross
      reacted with extracellular matrix components in immunohistochemistry of colon
      carcinoma, whereas the other scFv (VEL-2) specifically recognised colon cancer
      cells. The latter antibody was further characterised with respect to epitope
      specificity and kinetics of antigen-binding. It showed no competition with the
      well-characterised anti Ep-CAM MOC-31 monoclonal antibody and had an off-rate of
      5 x 10(-2) s-1. To obtain an antibody format more suitable for in vivo tumour
      targeting and to increase the apparent affinity through avidity, the genes of
      scFv VEL-2 were re-formatted by fusion to a human (gamma 1) hinge region and CH3
      domain. This "minibody" was expressed in Escherichia coli, specifically bound the
      Ep-CAM antigen and showed a 20-fold reduced off-rate in surface plasmon resonance
      analysis. These results show that phage antibody selection, combined with
      antibody engineering, may result in fully human antibody molecules with promising
      characteristics for in vivo use in tumour targeting.

PMID- 11315511
TI  - Neurological signs and sustained attention impairment in schizophrenia.
AB  - Both neurological signs and attention impairments are often found in
      schizophrenia. This study addresses the extent to which neurological signs are
      related to sustained attention impairment. We assessed subgroups of neurological
      signs using the standardised Cambridge Neurological Inventory (CNI). Sustained
      attention was measured using a monotone counting paradigm. After taking into
      consideration potential confounds such as age, education level and duration of
      illness, we explored the correlation between sustained attention and groups of
      neurological signs, as well as with individual signs. We found that "motor
      coordination" and "disinhibition" signs were significantly related to sustained
      attention. The correlation with "sensory integration" just failed to reach
      significance after correction for multiple comparison. "Dyskinesia", "catatonia",
      "pyramidal" and "extrapyramidal" subgroups were unrelated to sustained attention.
      The results support the notion of heterogeneity and diversity in neurological
      signs (even among soft neurological signs) and argue against the use of a single
      global measure to embrace all soft neurological signs in schizophrenia.

PMID- 11315512
TI  - Is mood-incongruent manic psychosis a distinct subtype?
AB  - BACKGROUND: Despite several research reports on incongruent psychotic features in
      mania, whether such features define a distinct disorder is unsettled. METHOD: One
      hundred and fifty-five inpatients with mania according to DSM-III-R were
      systematically evaluated in order to collect demographic and clinical
      information. The symptomatological evaluation was conducted by means of the
      Comprehensive Psychopathological Rating Scale (CPRS) and the Scale for the
      Assessment of Positive Symptoms (SAPS). The presence/absence of incongruent
      psychotic symptoms at the index episode defined two subgroups of patients, whose
      familial, symptomatological, clinical and course characteristics were compared.
      RESULTS: Eighty-six (55.5%) patients presented mood-incongruent psychotic
      features (MIP+). When this group was compared with the remainder of manic
      patients without such features (MIP-), we found substantial similarities in most
      demographic, familial and clinical characteristics. Despite these fundamental
      similarities, 4% of MIP+ vs 0% of MIP- had family history for schizophrenia (p <
      0.05). We also observed a longer duration of the current episode, a higher
      percentage of chronic course, more suicide attempts and hospitalisations in MIP+.
      Moreover, other than psychotic symptoms, MIP+ showed more frequently depressive
      features and hostility. They also reported higher scores in social disability,
      especially in family and social settings. CONCLUSION: Although our findings
      suggest that incongruent psychotic features in the main do not distinguish two
      separate entities--and can be considered as hallmarks of overall severity of
      mania--in a small minority of cases such features appear linked to familial
      schizophrenia. The numerous overlapping clinical characteristics in MIP+ and MIP-
      raise questions about the general nosographic utility of this categorisation.

PMID- 11315513
TI  - Effects of cerebral hemispheric laterality on the span of apprehension of
      schizophrenic and healthy subjects.
AB  - The effects of hemispheric laterality on a forced-choice Span of Apprehension
      (SoA) task were investigated. Forty-eight adult schizophrenic inpatients were
      recruited. A control group of healthy subjects was put together using the matched
      pairs method with age, gender, and education as control variables. SoA
      performance was determined separately for the left and right visual field (VF),
      respectively. No SoA group differences were found; in both groups, the hit
      percentage was higher in the right VF. However, in the schizophrenic group, the
      left VF performance showed significant negative correlations with
      psychopathologic symptoms (especially auditory verbal hallucinations). In a
      subsample of patients receiving atypical neuroleptic drugs, the daily dosage
      correlated negatively with left VF performance. In general, young subjects
      performed better than old subjects (both VFs), males performed better than
      females, and subjects with high education performed better than subjects with low
      education (right VF).

PMID- 11315514
TI  - Polymorphisms in the apolipoprotein E (APOE) gene in gerontopsychiatric patients.
AB  - Two recently described polymorphisms in the promoter region of the apolipoprotein
      E (APOE), the -491A/T and Th1/E47csT/G polymorphism, have been suggested to be
      associated with an increased risk for Alzheimer's disease (AD) independent from
      the APOE epsilon 4 carrier status. We studied the association between the APOE
      epsilon 4 polymorphism and the -491A/T and Th1E47csT/G polymorphisms in a sample
      of 118 healthy, non-demented controls and 239 consecutively recruited
      gerontopsychiatric patients diagnosed as: Alzheimer's disease (N = 89), age mild
      cognitive impairment (N = 32), memory complainers without any cognitive deficit
      (N = 54) and depression/other psychiatric disorders (N = 64), to test whether the
      investigated polymorphisms have a high enough selectivity and specificity to
      distinguish between the different gerontopsychiatric disorders or to
      differentiate AD genetically from other forms of dementia, respectively. Also a
      possible association with the APOE epsilon 4 polymorphism was examined. We found
      a statistically significant association between the APOE epsilon 4 allele and
      Alzheimer's disease (p = 0.0001) and age associated memory impairment (p =
      0.006). Our study failed to show an association between the promoter
      polymorphisms -491A/T and Th1E47csT/G in the APOE gene and gerontopsychiatric
      disorders either alone or in relationship to the APOE epsilon 4 polymorphism.
      However, if we combine our results with three previous published positive reports
      there seems to be an association between the -491A/T polymorphism and AD, though
      its size is less than found in the original publication.

PMID- 11315515
TI  - Sleep and sleep-wake cycle in an 81-year-old patient with de novo ultra-rapid
      cycling bipolar disorder.
AB  - This is a case report of an 81-year-old man who developed de novo bipolar
      disorder with ultrarapid cycling at the age of 80. Mood was self-rated daily over
      a period of ten weeks; in addition, polysomnographic and motor activity
      recordings were performed during a drug-free baseline period. Both depressive and
      hypomanic episodes had an average duration of about 30 hours; the affective cycle
      was thus independent from the sleep-wake cycle. When mood shifts occurred during
      nighttime, sleep was different in nights following depression than in nights
      following hypomania. Positron emission tomography revealed a moderate bilateral
      frontal hypermetabolism in the hypomanic phase and yielded normal findings for
      the depressive stage. In contrast to what is usually expected in ultra-rapid
      cycling bipolar disorder, this case demonstrates an unusual sleep-unrelated cycle
      duration in the oldest reported patient so far.

PMID- 11315516
TI  - Is 4 days the minimum duration of hypomania in bipolar II disorder?
AB  - DSM-IV requires that bipolar II disorder has hypomania with a minimum duration of
      4 days, a cutoff not based on data. The study aim was to test if hypomania
      lasting 2 to 3 days could identify a group of bipolar II with typical clinical
      features of bipolar disorders. Consecutively, 65 unipolar and 103 bipolar II
      major depressive episode (MDE) outpatients were interviewed with the Structured
      Clinical Interview for DSM-IV. Almost all had had 2 to 3 days of hypomania, and
      all had had more than one hypomania. Typical clinical variables distinguishing
      bipolar from unipolar disorders (age at onset, atypical features, and
      recurrences) were compared. Bipolar II had significantly lower age at onset, more
      recurrences, and more atypical features. Findings suggest that hypomania lasting
      2 to 3 days may identify a bipolar II group having typical features of bipolar
      disorders.

PMID- 11315517
TI  - Long-term effectiveness of a short-term cognitive-behavioral group treatment for
      primary insomnia.
AB  - The long-term effectiveness of a short-term cognitive-behavioral therapy was
      evaluated. The structured group treatment consisted of six weekly sessions and
      included progressive muscle relaxation, cognitive relaxation, modified stimulus
      control with bedtime restriction, thought stopping and cognitive restructuring.
      Twenty patients with chronic primary insomnia took part in the study. All
      patients were referred by physicians for diagnosis and therapy of insomnia.
      During a waiting period of six weeks prior to treatment, patients did not
      experience any change of their sleep parameters. After therapy, patients improved
      their total sleep time and sleep efficiency and reduced their sleep latency and
      negative sleep-related cognitions. Furthermore, depression scores decreased. Most
      of the treatment effects were significant at the end of the treatment and
      remained stable over the long-term follow-up, which was evaluated after a mean of
      almost three years (35 +/- 6.7 months). The subjective estimated total sleep time
      improved from 298 +/- 109 min prior to therapy to 351 +/- 54 min at the end of
      treatment, to 376 +/- 75 min at the 3-month follow-up, to 379 +/- 58 min at the
      12-month follow-up and to 381 +/- 92 min. at the long-term follow-up.

PMID- 11315518
TI  - Antecedents of opioid dependence and personality disorder: attention
      deficit/hyperactivity disorder and conduct disorder.
AB  - Both attention-deficit/hyperactivity disorder (ADHD) and conduct disorder (CD)
      were explored as possible antecedents of opioid dependence and personality
      disorder. One hundred adult opioid-dependent, treatment-seeking male inpatients
      were explored; an extended clinical semistructured interview to collect
      sociodemographic, drug use related, and clinical data and the Structured Clinical
      Interview for DSM-IV personality disorders SCID-II were carried out. Four groups
      of patients, namely ADHD alone (4 patients), ADHD + CD (7 patients), CD alone (47
      patients) and no ADHD/no CD (42 patients) were identified and compared with each
      other. The results indicate that ADHD alone does not predispose to the
      development of opioid dependence in male inpatients. Childhood ADHD may
      nevertheless be found more frequently in male opioid addicts due to its
      comorbidity with CD, which was identified in more than half of our sample.
      Patients with ADHD history seemed to go through the drug abuse career earlier and
      to develop more frequently histrionic and obsessive-compulsive personality
      disorder. Over half of the CD patients developed borderline and/or antisocial
      personality disorder; both ADHD and CD predispose significantly to the PD
      development. Early substance use preventive measures are necessary in children
      and adolescents suffering from CD and from ADHD comorbid with CD.

PMID- 11315519
TI  - Mood improvement reduces memory complaints in depressed patients.
AB  - BACKGROUND: The aim was to examine associations between memory complaints,
      cognitive performance and mood in 174 adult, clinically depressed, neurologically
      healthy patients at baseline and during six months of follow-up. METHODS:
      Subjective memory disturbance was assessed using the Memory Complaint
      Questionnaire (MCQ). Levels of cognitive function, including memory, were
      assessed using a battery of neuropsychological tests. Mood and personality traits
      were assessed using rating scales, including the Beck Depression Inventory (BDI),
      Hamilton Depression Rating Scale (HDRS) and the 90-item Symptom Check List (SCL
      90). RESULTS: At baseline, patients complaining of memory disturbances had higher
      BDI and HDRS scores than patients not complaining of memory problems. They also
      did less well in objective memory performances but not in other cognitive
      functions. Complaints of memory problems decreased during the follow-up. This
      change was associated with mood improvement and with reductions in other mental
      symptoms but not with changes in cognitive performance. In logistic regression
      analysis factors independently associated with MCQ change were age (OR 0.96) and
      BDI change (OR 1.06). CONCLUSIONS: Subjective memory problems usually decline if
      depression is alleviated.

PMID- 11315520
TI  - Use of polymerase chain reaction to identify Brucella abortus strain RB51 among
      Brucella field isolates from cattle in Italy.
AB  - Brucella abortus strain RB51, a rough mutant of the B. abortus 2308 virulent
      strain, was recently approved in the United States as the official vaccine for
      brucellosis in cattle. Following recent evidence of unauthorized use of RB51
      vaccine in Italy, where the use of vaccines for brucellosis is no longer allowed,
      the suitability of an RB51-specific polymerase chain reaction assay for
      identifying the RB51 strain among Brucella field isolates from cattle in Italy
      was investigated. The oligonucleotide primers used in this study, belonging to a
      six-primer cocktail for Brucella species previously described by other authors,
      allowed the amplification of a 364-base pair (bp) fragment specific for RB51 and
      its parent strain 2308, and a 498-bp product specific for B. abortus. In
      addition, unresolved bands ranging from 600 to 700 bp were observed from RB51
      strain. Brucella abortus biovars 1, 2 and 4 have only one specific sensitive 498
      bp band. The B. abortus biovars 3, 5 and 6 did not give any signal. The 498-bp
      product from a reference Brucella strain was sequenced and submitted to EMBL with
      the accession number AJ271969 while the 364-bp fragment from RB51 strain was
      submitted to EMBL database with accession number AJ271968. The sequence studies
      confirmed the specificity of the detected fragments. No amplification was
      obtained by testing DNA from strains antigenically related to Brucella, such as
      Yersinia enterocolitica O:9, Escherichia coli O:157, Salmonella urbana and
      Pasteurella multocida. The results of this study indicate that this technique, in
      combination with specific serological tests, could be a useful diagnostic method
      to verify the use of RB51 vaccine and can contribute to the creation of a
      databank of circulating strains.

PMID- 11315521
TI  - Antimicrobial susceptibilities of Erysipelothrix rhusiopathiae isolated from pigs
      with swine erysipelas in Japan, 1988-1998.
AB  - The susceptibility to 21 antimicrobial agents of 214 strains of Erysipelothrix
      rhusiopathiae isolated from pigs affected with swine erysipelas in Japan between
      1988 and 1998 was determined. Ampicillin, cloxacillin, benzylpenicillin,
      ceftiofur, tylosin, enrofloxacin and danofloxacin were the most active agents
      [minimum inhibitory concentrations (MICs); < or = 0.025-0.78 microgram/ml],
      followed by cefazolin, virginiamycin, tiamulin, chloramphenicol, florphenicol and
      oxolinic acid (MICs; 0.1-25 micrograms/ml). Activity was poor or absent with
      kanamycin and sulfadimethoxine. Strains resistant to dihydrostreptomycin,
      erythromycin, clindamycin, lincomycin, oxytetracycline and doxycycline were
      detected. The susceptibilities to dihydrostreptomycin and oxytetracycline tended
      to decrease. Investigation of the differences in antimicrobial susceptibility of
      the 214 strains according to their serotypes, sources, isolation years and
      regions, showed that the strains resistant to dihydrostreptomycin were most
      frequently found in the strains of serotype 1a and in strains from septicaemic
      cases. Strains resistant to oxytetracycline were detected in all serotypes and
      all sources, and most of the strains resistant to erythromycin were detected in
      the strains of serotype 2. The frequency of strains resistant to
      dihydrostreptomycin gradually increased from 1988 to 1996, but then decreased
      between 1997 and 1998. The frequency of strains resistant to oxytetracycline was
      remained more than 38% from 1988 to 1998. It was suggested that the strains
      resistant to dihydrostreptomycin and oxytetracycline were distributed over almost
      all districts of Japan.

PMID- 11315522
TI  - Pathogenicity of Actinobacillus minor, Actinobacillus indolicus and
      Actinobacillus porcinus strains for gnotobiotic piglets.
AB  - The purpose of the study was to evaluate the clinical significance of
      Actinobacillus minor, Actinobacillus porcinus and Actinobacillus indolicus
      strains in gnotobiotic piglets. Twenty-two 6-h-old Caesarean-delivered and
      colostrum-deprived piglets were intranasally and orally inoculated with 2 x 10(6)
      colony-forming units of an A. minor (group 2; n = 9), A. indolicus (group 3; n =
      5), or A. porcinus (group 4; n = 8) strain. Six other piglets were inoculated in
      the same way with phosphate-buffered saline solution and used as controls (group
      1). All pigs were observed for clinical signs and rectal temperatures were taken
      until euthanasia 7 days after inoculation. At necropsy, conchae, tonsils, lungs,
      brains, liver, spleen and kidneys were macroscopically examined for lesions and
      samples were taken for bacteriology. None of the pigs developed fever. Mild
      ataxia was observed in one pig from group 3 for 2 days. Clinical signs were not
      observed in the other animals. In none of the animals were macroscopic lesions
      detected at necropsy. NAD-dependent Pasteurellaceae were not isolated from
      control animals (group 1). The A. minor, A. indolicus and A. porcinus strains
      were isolated from the tonsils of one, two and one pigs, respectively.
      Actinobacillus porcinus was isolated from the brains of the pig with central
      nervous symptoms and from the conchae of another pig. The inoculation strains
      were not demonstrated in the other samples. It was concluded that, using these
      inoculation routes and dose, the A. minor, A. indolicus and A. porcinus strains
      had low capacity to colonize the upper respiratory tract of gnotobiotic piglets
      and demonstrated low or no pathogenicity in such animals.

PMID- 11315523
TI  - Keratoconjunctivitis and periorbital papillomatosis associated with heavy
      periorbital infestation by the tail louse Haematopinus quadripertusus in heifers.
AB  - Heifers (Israeli-Holstein), aged 12-18 months, permanently maintained in open
      barns on an inadequate nutritional regime were found to be moderately to heavily
      infested by Haematopinus quadripertusus, the tail louse. The severely infested
      heifers showed keratoconjunctivitis and periorbital papillomatosis. Two
      treatments with an alpha-cypermethrin pour-on product 14 days apart controlled
      the lice, and were followed by alleviation of the inflammation and regression of
      the papillomas.

PMID- 11315524
TI  - Infectious bovine keratoconjunctivitis and lymphofollicular hyperplasia of the
      third eyelid in heifers.
AB  - On a dairy cattle farm, infectious bovine keratoconjunctivitis was diagnosed in
      29 (24%) calves and heifers aged from 2 weeks to 1 year old. The highest
      infection rate (18%) occurred in animals aged 3-6 months. The bacteriological
      examination of swabs from the affected animals yielded several species of
      bacteria: Moraxella bovis, Neisseria ovis, N. cuniculi, plasma coagulase-negative
      Staphylococcus spp., alpha-haemolytic Streptococcus spp., Arcanobacterium
      pyogenes and Escherichia coli. Moraxella bovis and N. ovis were the most common
      isolates. Hyperplasia of the lymphatic tissue of the third eyelid in the form of
      nodules 7-8 mm in diameter was diagnosed in two heifers aged 8 and 10 months.

PMID- 11315525
TI  - Descriptive epidemiology of a classical swine fever outbreak in the Limburg
      Province of Belgium in 1997.
AB  - This paper describes the epidemiological characteristics of the 1997 Classical
      Swine Fever (CSF) outbreak that occurred in the Limburg Province of Belgium,
      where there is a policy of non-vaccination, intensive surveillance and
      eradication. Between 30 June and 17 July 1997, eight herds, located in three
      different areas, were confirmed to be CSF-positive. CSF virus was transmitted
      from the primary infected herd of one area to another five herds in the same area
      and to one herd in a different area. The mode of virus introduction for this
      primary infected herd and for the one herd that was not infected by this primary
      herd could not be determined. Clinical, serological, and virological findings
      indicated that the CSF-infected herds were detected in an early stage of the
      infection. The early detection of the infection together with a preventive
      stamping out procedure resulted in a rapid elimination of the CSF virus. A total
      of 46,561 pigs were slaughtered to control the spread of the infection. Another
      27,579 pigs were slaughtered in the framework of the market support. The total
      direct costs of the episode were estimated at [symbol: see text] 10,893,337.

PMID- 11315526
TI  - Prevalence of enteropathogens in suckling and weaned piglets with diarrhoea in
      southern Germany.
AB  - Faecal samples from suckling (n = 205) and weaned piglets (n = 82) with diarrhoea
      from 24 farms in Southern Germany were examined for shedding of important
      metazoic parasitic, viral and bacterial pathogens using culture, microscopic and
      electronmicroscopic methods. Escherichia coli isolates were tested further for
      the enterotoxin genes est-Ia and elt-I by colony blot hybridization. Isospora
      suis was diagnosed in 26.9% and Cryptosporidium parvum in 1.4% of the piglets
      investigated. The proportion of coronavirus-positive animals was 13.4% and 4%
      were positive for rotavirus. It was found that 17.6% of the animals were infected
      with enterotoxigenic E. coli (ETEC; 10.1% ETEC-ST-Ia and 8.6% ETEC-LT-I,
      respectively). The occurrence of the pathogens was significantly associated with
      the age of the animals examined (P < 0.001). Isospora suis was predominantly
      isolated from suckling piglets (in the second and third week of life), while in
      weaned piglets (fourth week of life) rotavirus and ETEC were most prevalent. On
      22 of the 24 piglet production farms examined at least one of the investigated
      pathogens was detected. Coronavirus was diagnosed in 66.7%, I. suis in 62.5%,
      rotavirus in 20.8% and C. parvum in 8.3% of the farms. These results underline
      the fact that despite the hygienic, technical and immune preventive efforts
      during the last years, enteropathogens are still common in German piglet
      production units.

PMID- 11315527
TI  - Differences in lymphocyte subpopulations from peripheral blood and lymphoid
      organs in natural caprine tuberculosis infection.
AB  - Although the cell-mediated immune response is known to be a critical factor in
      host defence against intracellular mycobacterial infection, the different
      components of the T-cell response are unclear, particularly in caprine infection.
      In this study we examine the differences in the lymphocyte population of
      peripheral blood, spleen and mediastinal and superficial lymph nodes in 11
      naturally infected goats showing positive reactions in the comparative
      tuberculine intradermal test. According to the different types of lesion showing,
      the goats were classified into proliferative or exudative tuberculosis. The
      results obtained by fflow cytometry analysis indicated that the main differences
      in peripheral blood were in the CD4 T-cell population, which decreased markedly
      in goats with exudative tuberculosis, while the CD8 and B cells increased in
      number. The gamma/delta T cells did not show significant differences in either
      type of tuberculosis, while interleukin-2 receptor cells decreased slightly in
      the exudative tuberculosis. The CD4:CD8 ratio was higher than 1 in goats with
      proliferative tuberculosis and lower than 1 in goats with exudative tuberculosis.
      In general, the lymphoid organs of the goats with exudative tuberculosis showed a
      significant increase in the number of CD8 T cells (CD4:CD8 ratio of less than 1)
      whereas no significant differences were observed in the CD4 T population between
      either type of tuberculosis.

PMID- 11315528
TI  - Detection of antibodies to ovine lentivirus using recombinant capsid and
      transmembrane proteins.
AB  - The coding sequences of the capsid protein p25 and transmembrane protein of Maedi
      Visna virus were amplified using polymerase chain reaction and cloned into the
      plasmid expression vector pRSET-B. Both DNA constructs expressed proteins tagged
      with polyhistidine. The recombinant proteins were purified using Ni-NTA agarose
      and used in immunoblot to detect antibodies against Maedi-Visna virus. A total of
      260 ovine serum specimens was analysed. The total number of p25-positive sera was
      111 (42.7%). Higher sensitivity was achieved with rTM antigen, which detected
      antibodies in 118 (45.4%) sera. The combination of both recombinant proteins as
      antigens resulted in higher sensitivity of serological detection compared to
      whole virus antigen.

PMID- 11315529
TI  - Comparative study of PCR as a direct assay and ELISA and AGID as indirect assays
      for the detection of bovine leukaemia virus.
AB  - The choice of a diagnostic method depends on the characteristics of the herd to
      be analysed. Two herds with different prevalences of enzootic bovine leukaemia
      were chosen to study the concordance between agar gel immunodiffusion (AGID),
      enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR)
      methods. PCR, an increasingly used virological method, was performed with four
      sets of primers, amplifying different genomic regions (env, pol and tax), from
      DNA extracted either from peripheral blood monocytes (PBMCs) or milk leucocytes.
      The highest percentage of positive animals was obtained using PCR performed with
      DNA extracted from PBMCs using primers which amplified either env or pol,
      followed by PCR using PBMCs and primers which hybridized with tax, then ELISA
      using serum and finally AGID. The results of PCR were more consistent with PBMCs
      than when milk leucocytes were used.

PMID- 11315530
TI  - Associations between disturbed sleep and behavioural difficulties in 635 children
      aged six to eight years: a study based on parents' perceptions.
AB  - Associations between sleep and behaviour in 635 children, aged six to eight
      years, were investigated using parental responses to a sleep habits
      questionnaire, and to a behavioural screening form, the Strengths and
      Difficulties Questionnaire (SDQ). Global reports of sleep problems in 4.9% of the
      children were associated with a total SDQ score indicative of behaviour problems
      in 36% of the cases. Conversely, 15% of children with behaviour problems had
      global reports of sleep problems. Associations between specific sleeping features
      and different dimensions of behaviour and emotions were also explored.
      Hyperactivity was associated with tossing and turning during sleep, and with
      sleep walking; conduct problems were related to bedtime resistance; and emotional
      symptoms were associated with night terrors, difficulty falling asleep and
      daytime somnolence. Peer problems were associated with somewhat shorter total
      sleep time. Finally, a total SDQ score indicative of behaviour problems was
      associated with bedwetting, nightmares, tossing and turning during sleep and
      sleep walking, as well as with a slightly shorter total sleep time. We conclude
      that sleep and behaviour problems are associated in children, and that
      characteristic associations exist between particular sleep disturbances and
      specific dimensions of behaviour.

PMID- 11315531
TI  - A study of posttraumatic disorders in children who experienced an industrial
      disaster in the Briey region.
AB  - OBJECTIVES: To study posttraumatic disorders in children who were directly and
      indirectly involved in an industrial disaster; to assess the respective impact of
      traumatism exposure, parental disorders and sociodemographic variables on the
      posttraumatic disorders of the children. METHODS: The children were assessed with
      self-administered questionnaires (STAIC, CDI, IES) and questionnaires filled in
      by parents (CPRS, CBCL). Parents were assessed with the GHQ-28. Forty-three
      exposed children were compared with 44 children who were exposed to the same risk
      (indirectly exposed group) and with a control group of 50 unexposed children.
      RESULTS: The exposed group obtained significantly higher anxiety and trauma
      related scores than the control group and the threatened group, as well as higher
      scores of behavioural symptoms and of parental disorders. Indirectly exposed
      children did not have higher rates of symptoms than control children. The younger
      exposed children exhibited the highest psychopathological scores. Low
      sociodemographic status was associated with more disorders. There were no
      differences on questionnaire scores between girls and boys. Children's disorders
      correlated with disorders in both parents; but this only accounted for part of
      the variance, a finding which supports the hypothesis of a direct impact of the
      trauma on the child, irrespective of parental clinical status, SES of the family,
      children's age and gender. CONCLUSIONS: Children's and parent's disorders
      interact in a complex fashion which needs further study.

PMID- 11315532
TI  - Conduct problems in Russian adolescents: the role of personality and parental
      rearing.
AB  - The purpose of the present study was 1) to assess the predictive value of conduct
      problems prior to the age of 12 for the severity of antisocial behaviour during
      adolescence, and 2) to investigate the relationships between personality
      traits/parental rearing and childhood conduct problems/teenage antisocial
      behaviour. A group of 193 delinquents was assessed by means of the Antisocial
      Behavior Checklist (ABC), the Retrospective Childhood Problems (RETROPROB), the
      Temperament and Character Inventory (TCI) and the EMBU questionnaire on parental
      rearing. The extreme groups of delinquents as defined by childhood conduct
      problems, differed significantly on the experience of a rejecting father and a
      self-directed character. Furthermore, some specific predictive patterns for
      current antisocial behaviour by childhood conduct disorder and both personality
      dimensions and parental rearing factors emerged. The findings are discussed in
      the light of the interactive nature of relations between personality and parental
      rearing in the development of antisocial behaviour among adolescents.

PMID- 11315533
TI  - Children with persistent conduct problems who dropout of treatment.
AB  - Dropout of treatment is one of the key issues in outcome in a child and
      adolescent mental health service. We report two studies focusing on the treatment
      process and the dropout rate of children with persistent conduct problems
      presenting to a community mental health service, using a prospective design. The
      first study included 32 children and used a randomised controlled treatment
      design comparing a CBT approach with conjoint family therapy and an eclectic
      approach. The overall dropout rate was 36%. Dropout occurred significantly less
      frequently in the CBT group. The dropout group was associated with mothers who
      were younger and less educated, a poorer rating by the clinicians at the last
      meeting, parental dissatisfaction with the treatment service and perception that
      the treatment was less organised and having less behavioural tasks. In the second
      study we used a naturalistic follow-up design. Forty-six children were included.
      The overall dropout rate was 48%. Again, the children who defaulted were rated by
      clinicians as less likely to have improved and dropout was also significantly
      associated with parental perception of a less organised treatment. In both
      studies dropout usually occurred after assessment and at the early phase of
      treatment.

PMID- 11315534
TI  - Long-term outcome and prognosis of obsessive-compulsive disorder with onset in
      childhood or adolescence.
AB  - The aim of the catch-up follow-up study is to describe the long-term outcome of
      obsessive-compulsive disorder (OCD) with onset in childhood and adolescence. The
      psychiatric morbidity in adulthood including personality disorders was assessed
      and predictors in childhood for the course of obsessive-compulsive symptoms were
      examined. The total study group consisted of the entire patient population
      treated for OCD at our departments for child and adolescent psychiatry between
      1980 and 1991. We reassessed 55 patients personally by way of structured
      interviews. The mean age of onset of OCD was 12.5 years and the mean follow-up
      time was 11.2 years. At the follow-up investigation 71% of the patients met the
      criteria for some form of psychiatric disorder, while 36% were still suffering
      from OCD. Of the patients with a present diagnosis of OCD 70% had at least one
      further clinical disorder (especially anxiety and affective disorders). The most
      frequent personality disorders diagnosed were obsessive-compulsive (25.5%),
      avoidant (21.8%), and paranoid (12.7%) personality disorders. In-patient
      treatment, terminating treatment against advice and tics in childhood or
      adolescence significantly correlated with more severe OC symptoms in adulthood.

PMID- 11315535
TI  - The standardization of Achenbach's Youth Self-Report in Greece in a national
      sample of high school students.
AB  - Achenbach's Youth Self Report (YSR) questionnaire is accepted worldwide for the
      assessment of adolescent competencies and behaviour problems. As with any similar
      instrument, it is liable to cultural influences, hence requires standardization
      for the culture in which it is to be used. This study reports on the
      standardization of the YSR in Greece, in a national school-based sample of 1456
      high school students, 11-18 years of age. Responses at the item level seem to
      follow the culturally expected gender behaviour. Behaviour problem scale scores
      were not affected by degree of urbanization, reflecting a high degree of cultural
      homogeneity between urban and rural areas in Greece. Sex effects were important,
      with girls showing a greater tendency towards Internalizing and boys towards
      Externalizing Problems. Age effects were also statistically significant (older
      adolescents showing more problems, especially of the delinquent type), but
      numerically small. There was considerable correlation between Internalizing and
      Externalizing problems, with an odds ratio of 6.9 (95% confidence interval, 4.6
      10.4) for exceeding both cut-offs. The analysis showed that Greek adolescents
      obtained significantly higher mean scores than their American counterparts on all
      scales. Cut-off points based on the 90th and 98th percentile developed from this
      sample are presented for the competencies and the problem scales.

PMID- 11315536
TI  - Pericardial effusions in anorexia nervosa.
AB  - Anorexia nervosa is an eating disorder that may be accompanied by cardiac
      symptoms of varying severity. So far disturbances like arrhythmias, mitral valve
      prolapse and loss of cardial ventricle mass have been described. Other somatic
      complications consist of electrolyte and acid-base imbalances, which in turn
      influence cardiac function. Between 1990 and 1999 we observed ten case reports
      from inpatient anorexic female adolescents, who developed pericardial effusions
      in the course of their illness. The diagnosis and course was revealed by
      echocardiography. No signs of heart failure could be noticed. In eight patients
      pericardial effusion remitted completely or partly by a concurrent increase in
      weight. A distinct pathophysiology for the development of pericardial effusion
      could not be revealed, but a correlation to restoration of weight seems to exist.
      Our report suggests that pericardial effusions are more frequent cardiac
      complications in anorexia nervosa than previously known. In most cases the
      clinical significance is doubtful.

PMID- 11315537
TI  - Evaluation of attention problems in children with autism and children with a
      specific language disorder.
AB  - Children with autism and children with a specific language disorder show
      additional attention deficits. The literature on the neuropsychological
      investigation of attention in both groups of children suggests that the nature of
      their attention problems might be different. The purpose of this study is to
      examine the attention test profiles in these two groups of children with
      developmental disorders. Nineteen children and adolescents with autism, 17
      subjects with a specific language disorder and 19 control subjects participated
      in the study. Non-verbal intelligence was normal for all subjects. The
      "Testbatterie zur Aufmerksamkeitsprufung" was administered to all subjects. This
      instrument provides the possibility to examine a wide range of attention
      functions and executive functions. The results showed that the autistic
      individuals had deficits in executive functions, whereas the language impaired
      children had deficits in auditory sustained attention, in auditory selective
      attention, and in the domain of executive functions. It is concluded that
      although both groups of developmentally impaired subjects showed attention
      problems, the deficits are not the same in both groups. The different
      neuropsychological profiles probably reflect different mechanisms in the
      pathogenesis of the attention deficits in both types of developmental disorders.

PMID- 11315538
TI  - Autistic disorder versus other pervasive developmental disorders in young
      children: same or different?
AB  - Eighteen preschool children diagnosed according to the Diagnostic and Statistical
      Manual of Mental Disorders Third Edition Revised (DSM III-R) as having Pervasive
      Developmental Disorder-Not Otherwise Specified (PDD-NOS) were compared to 176
      children with DSM III-R Autistic Disorder (AD), and to 311 non-autistic children
      with developmental language disorders (DLD) (N = 201) or low IQ (N = 110). All
      children were partitioned into "high" and "low" cognitive subgroups at a
      nonverbal IQ of 80. Within cognitive subgroups, the 18 PDD-NOS children did not
      differ significantly from either the DLD or the AD children in verbal and
      adaptive skills and obtained scores intermediate between those of these groups.
      The PDD-NOS did not differ from the AD children in maladaptive behaviors. Both
      the PDD-NOS and AD children had many more of these behaviors than the non
      autistic comparison groups. Children in the "high" and "low" cognitive subgroups
      of AD, but not of PDD-NOS, differed substantially on most measures, with the
      children with lower cognitive scores significantly more impaired on all measures.
      Similarity of PDD-NOS children to AD children in maladaptive behaviors and an
      intermediate position between autistic and non-autistic groups on virtually all
      measures explains the difficulty clinicians encounter in classifying children
      with PDD and raises questions about the specificity of these diagnostic subtypes
      of the autistic spectrum.

PMID- 11315539
TI  - Disordered recognition of facial identity and emotions in three Asperger type
      autists.
AB  - In this report we aim to explore severe deficits in facial affect recognition in
      three boys all of whom meet the criteria of Asperger's syndrome (AS), as well as
      overt prosopagnosia in one (B) and covert prosopagnosia in the remaining two (C
      and D). Subject B, with a familially-based talent of being highly gifted in
      physics and mathematics, showed no interest in people, a quasi complete lack of
      comprehension of emotions, and very poor emotional reactivity. The marked
      neuropsychological deficits were a moderate prosopagnosia and severely disordered
      recognition of facial emotions, gender and age. Expressive facial emotion, whole
      body psychomotor expression and speech prosody were quasi absent as well. In all
      three boys these facial processing deficits were more or less isolated, and
      general visuospatial functions, attention, formal language and scholastic
      performances were normal or even highly developed with the exception of deficient
      gestalt perception in B. We consider the deficient facial emotion perception as
      an important pathogenetic symptom for the autistic behaviour in the three boys.
      Prosopagnosia, the absent facial and bodily expression, and speech prosody were
      important but varying co-morbid disorders. The total clinical picture of non
      verbal disordered communication is a complex of predominantly bilateral and/or
      right hemisphere cortical deficits. Moreover, in B, insensitivity to pain,
      smells, noises and internal bodily feelings suggested a more general emotional
      anaesthesia and/or a deficient means of expression. It is possible that a limbic
      component might be involved, thus making affective appreciation also deficient.

PMID- 11315540
TI  - Characteristics of children and parents attending a British Primary Mental Health
      Service.

PMID- 11315541
TI  - Reflex adaptations during treadmill walking with increased body load.
AB  - Load dependent reflex adaptations were studied in healthy subjects walking on a
      split-belt treadmill. Compensatory reflex responses were elicited in the right
      leg extensor muscles during mid-stance by a short acceleration of the right
      treadmill belt. Electromyographic activity (EMG) was recorded from the right
      medial gastrocnemius (GMR), soleus (SO) and tibialis anterior (TA) muscles of the
      right leg as well as from the gastrocnemius of the left unperturbed leg (GML). To
      study the adaptational reflex behavior, multiple measurements were taken during
      walking with normal (control) and increased body load and after removing the
      load. In most experiments the compensatory EMG response in the GMR consisted of a
      short inhibitory and a subsequent excitatory component. Both reflex components
      were larger when the body was loaded. During the course of continuous loading,
      divergent reflex adaptations of different degrees and directions were observed in
      the subjects. In one group of subjects the reflex response increased to a higher
      level of EMG activity. In a second group EMG activity first increased and
      afterwards decreased to baseline level. A subsequent removal of body loading
      resulted in a slow adaptation to the control reflex values in both groups.
      Neither the EMG activity in the GM nor the reflex responses in the GMR after
      increasing the load changed differently in the two groups. Our results suggest
      that load information is not simply used in a fixed input/output relationship of
      the actual biomechanical conditions of a subject. Load information is rather used
      to slowly modify the reflex response, to achieve the desired posture during
      walking.

PMID- 11315542
TI  - Parvalbumin and calbindin D-28K immunoreactive neurons in area MT of rhesus
      monkey.
AB  - The chemical characteristics of the neurons of the motion sensitive visual area,
      area MT, remain to be established. We studied the distribution pattern of two
      calcium binding proteins, parvalbumin (PV) and calbindin D28K (CB) in this area,
      using specific monoclonal antibodies and the peroxidase-antiperoxidase (PAP)
      immunohistochemical technique. Aldehyde fixed 30-micron-thick cryostat sections
      from area MT of five animals were processed free floating for immunohistochemical
      staining. Besides studying the morphological characteristics of PV and CB
      positive neurons, quantitative analysis was carried out to determine their (1)
      perikaryal area (Pa) and diameter, (2) numerical densities (NV)/mm3 cortical
      tissue, (3) absolute number (NC) in a column of cortex under 1 mm2 cortical
      surface along with (4) layerwise absolute number (NL) under 1 mm2 cortical
      surface and (5) laminar percentage distribution of immunoreactive (IR) neurons.
      Quantitative analysis was carried out using a Leica QMC 500 image analysis system
      connected to a DMRE microscope. The results showed that both types of IR neurons
      were localized to all cortical layers except layer I. The PV +ve neurons were
      equidistributed between the supra- and infragranular layers, with the highest
      percentage being present in layer III (45%) followed by layer V (21%). The CB +ve
      neurons, on the other hand, were predominantly localized in supragranular layers,
      with the highest percentage being in layer III (54%) and the next highest
      percentage in layer II (18%). The average Pa and diameter of PV +ve neurons were
      found to be 96.90 +/- 28.43 micron 2 and 11.01 +/- 1.61 microns respectively. The
      CB +ve neurons were significantly smaller in size than the PV +ve neurons, with
      average Pa and diameter of the former being 92.23 +/- 26.18 micron 2 and 10.39 +/
      1.23 microns respectively. The NV for PV and CB +ve neurons showed ranges of
      3157-3894 and 2303-2585, with means of 3347 +/- 285 (+/- SD) and 3436 +/- 100
      respectively. The values for NC showed ranges of 5230-5444 and 4020-4268 with
      means of 5378 +/- 85 and 4167 +/- 95 for PV and CB neurons respectively.
      Variations in size together with the differential distribution of these neurons
      in the cortical layers may indicate their involvement in different functional
      circuitaries.

PMID- 11315543
TI  - Quantitative ultrastructure of synapses on functionally identified primary
      afferent neurons in the cat trigeminal mesencephalic nucleus.
AB  - Though a number of studies have reported the presence of synapses on neurons in
      the trigeminal mesencephalic nucleus (Vmes), there have been no quantitative
      studies of either the density of innervation, or the ultrastructure, of the
      synapses on single, physiologically identified neurons in this nucleus. In this
      study we recorded from single neurons in the Vmes, identified them as being
      either muscle spindle afferents (MS) or periodontal ligament mechanoreceptor
      afferents (PL), and then labeled the neurons by intra-axonal injection of
      horseradish peroxidase (HRP). The material was first processed to reveal the HRP
      activity, following which ultrathin sections through the labeled somata were cut
      and examined under the electron microscope. Complete serial reconstructions were
      made through the soma of one MS neuron and one PL neuron, and the contacts on the
      neurons reconstructed. Boutons were found on the soma, spines, appendages and the
      axon hillock and the initial segment of the axon. The numbers of boutons
      terminating on the two neurons were 198 (PL) and 424 (MS), giving a packing
      density of 4.4 and 10.7 boutons respectively (i.e., number of boutons/100 micron
      2 of the postsynaptic membrane). Boutons could be separated into two types on the
      basis of their vesicles: those containing clear, round vesicles (i.e., S-type)
      and those containing a mixture of round, oval and flattened vesicles (P-type).
      Ninety-five (PL neuron) and 99% (MS neuron) of terminals on the two neurons were
      P-type. All the S-type boutons and 80% of the P-type boutons formed asymmetric
      synaptic contacts while 10% of the P-type boutons made symmetric contacts.
      Quantitative measurements of the P-type boutons on the labeled neurons, in which
      the data of MS and PL neurons were pooled, revealed that bouton volume was highly
      correlated with bouton surface area, active zone number, total active zone area,
      vesicle number, and mitochondrial volume. However, comparing the quantitative
      measurements of the P-type boutons with those of previously reported vibrissa
      afferent terminals and their associated axon terminals revealed that all the
      parameters were smaller for the P-type boutons (on Vmes neurons) than those of
      the vibrissa afferent terminals but similar to those of axon terminals
      presynaptic to the vibrissa afferents. Taken together, our results emphasize the
      wide scope for synaptic interactions in the Vmes and suggest that it may be more
      fruitful to view the Vmes as an integrating center.

PMID- 11315544
TI  - Mechanisms of decreased motoneurone excitation during passive muscle stretching.
AB  - The effect of pre- versus postsynaptic mechanisms in the decrease in spinal
      reflex response during passive muscle stretching was studied. The change in the
      electromyographic (EMG) responses of two reflex pathways sharing a common pool of
      motoneurones, with (Hoffmann or H reflex) or without (exteroceptive or E reflex)
      a presynaptic inhibitory mechanism, was compared. The EMG activities were
      recorded in the soleus muscle in response to the electrical stimulation of the
      tibial nerve at the popliteal fossa (H reflex), and at the ankle (E reflex) for
      different dorsiflexion angles of the ankle. The compound muscle action potential
      (M wave) in the soleus and the abductor hallucis was recorded in order to control
      the stability of the electrical stimulation during stretching. The results
      indicate that in the case of small-amplitude muscle stretching (10 degrees of
      dorsiflexion), a significant reduction (-25%; P < 0.05) in the Hmax/Mmax ratio
      was present without any significant change in the Emax/Mmax ratio. At a greater
      stretching amplitude (20 degrees of dorsiflexion), the E reflex was found to be
      reduced (-54.6%; P < 0.001) to a similar extent as the H reflex (-54.2%). As soon
      as the ankle joint returned to the neutral position (ankle at 90 degrees), the
      two reflex responses recovered their initial values. In additional experiments,
      motor-evoked potential (MEP) induced by the magnetic stimulation of the motor
      cortex was recorded and showed a similar type of behaviour to that observed in
      the E reflex. These results indicate that reduced motoneurone excitation during
      stretching is caused by pre- and postsynaptic mechanisms. Whereas premotoneuronal
      mechanisms are mainly involved in the case of small stretching amplitude,
      postsynaptic ones play a dominant role in the reflex inhibition when larger
      stretching amplitude is performed.

PMID- 11315545
TI  - Voluntary head stabilisation in space during oscillatory trunk movements in the
      frontal plane performed before, during and after a prolonged period of
      weightlessness.
AB  - The ability to voluntarily stabilise the head in space exhibited by two subjects
      during lateral rhythmic oscillations of the trunk has been investigated before,
      during and after a prolonged period of microgravity (microG) exposure. In flight
      acquisitions were performed onboard the Core Module of the Russian Space Station
      MIR as part of the T4 "Human Posture in Microgravity" experiment of the 179-days
      ESA-RKA mission EUROMIR-95. Data collection and kinematic analysis were performed
      by means of a space-qualified version of the automatic motion analyser ELITE.
      Head stabilisation in space strategy was estimated by means of the head anchoring
      index and cross-correlation analysis. Results show that head orientation may be
      well stabilised about the roll axis both with and without the presence of visual
      information. This was true despite the expected reduction in vestibular
      efficiency and muscular proprioception occurring in-flight. In one subject,
      however, vision was found to improve head stabilisation in space post-flight,
      presumably to recover from the postural deficiency induced by the long-term
      microG exposure. Head stability during trunk movements was achieved with either
      over-compensatory (out-of-phase), under-compensatory (in-phase) or mixed movement
      strategies, as was attested by the analysis of cross-correlation functions
      between head and shoulder movements. In weightlessness, vision occlusion seemed
      to influence the choice of the strategies to be used as well as the reduction of
      movement variability. The feedforward nature of compensatory head movements
      suggests that head stabilisation could be based in weightlessness on the internal
      postural body scheme, supposed to be adapted to the weightless environment within
      5 months of microG exposure.

PMID- 11315546
TI  - Persistence of vibrissal motor representation following vibrissal pad
      deafferentation in adult rats.
AB  - The effect of sensory vibrissal pad denervation on M1 organization was studied in
      adult rats 2 weeks after the infraorbital nerve was severed. Cortical motor
      output organization was assessed mapping the representation size and thresholds
      of vibrissa movements evoked by intracortical electrical microstimulation (ICMS).
      Motor cortex output patterns of control and sham groups of rats were compared
      with those of rats that had received unilateral or bilateral infraorbital nerve
      lesions. The mean size of the vibrissa representation in both unilateral and
      bilateral input-deprived hemispheres was not significantly different from those
      in control and sham hemispheres. The mean threshold required to evoke vibrissa
      movements was significantly higher in both groups of deafferented hemispheres
      than in control and sham groups of hemispheres. In contrast, the mean threshold
      required to evoke other types of movements from both groups of input-deprived
      hemispheres were similar to those found in the control and sham groups of
      hemispheres. These results indicate that input-deprived vibrissal motor
      representation reflects lower-than-normal excitability, although the size and
      topographic relationship with neighboring representations are normal.

PMID- 11315547
TI  - Plane-specific brainstem commissural inhibition in frog second-order semicircular
      canal neurons.
AB  - Commissural inputs of identified second-order semicircular canal neurons were
      studied by separate stimulation of each of the three canal nerves on either side
      in the vitro frog brains. The spatial pattern of these inputs was further
      investigated in those second-order canal neurons that received a monosynaptic
      input from only one ipsilateral canal nerve (91%). Since similar results were
      obtained in the presence as in the absence of the cerebellum, commissural inputs
      must have been relayed via fibers crossing in the brainstem. Following
      stimulation of individual semicircular canal nerves, commissural inputs were
      either inhibitory or excitatory. A commissural inhibition was evoked in the
      majority of the recorded neurons (79%) by stimulation of the coplanar
      semicircular canal nerve on the contralateral side. In the remaining neurons, a
      commissural excitatory input was evoked. A commissural excitation, originating
      from the two noncoplanar semicircular canals, predominated in most (68%) of the
      recorded neurons and was independent of the type of second-order canal neuron.
      The onset latency of the canal plane-specific commissural inhibitory potentials
      was di- or trisynaptic. Stimulation of the contralateral VIIIth nerve evoked
      excitatory commissural responses. The canal plane-specific commissural inhibition
      therefore might have been masked by commissural excitatory responses as in
      earlier studies. The similar organization of the canal plane-specific commissural
      inhibition in frog and cat corroborates the notion of a phylogenetically
      conservative, basic vestibular organization. The presence of a canal plane
      unspecific commissural excitation, however, appears to be a feature that is
      specific to frogs. The functional implications of these similarities and
      differences are discussed.

PMID- 11315548
TI  - In a complex sequential movement, what component of the motor program is improved
      with intensive practice, sequence timing or ensemble motor learning?
AB  - We investigated whether the higher maximum speed of complex athletic movements
      attained by experts compared with novices might solely be ascribed to the
      acquisition of a more efficient timing of the initiation of the simple movements
      that comprise complex sporting gestures. Six novices in fencing and five experts
      in fencing performed three experimental series: 7 trials of touche, 7 trials of
      lunge (control series) and 50 trials of lunge + touche (test series), where the
      touche and lunge were initiated with different chronological sequences imposed by
      the experimenter. The lunge and the touche can be assimilated to a fast forward
      step and to a pointing task, respectively. We compared the maximum speed of
      touche between the two groups, recorded by an accelerometer fixed to the hand
      guard of the foil, and the speed of the centre of mass obtained from a force
      plate. The speed of the centre of mass was not statistically different between
      the two groups in the control and in the test series. The maximum speed of touche
      was not statistically different between the two groups in the control series. In
      contrast, in the test series, the maximum speed of touche was higher in the
      fencers' than in novices' groups, while the timing of initiation of the lunge and
      the touche was similar. The results of the test series show that the higher
      maximum speed of touche of fencers compared with novices cannot solely be
      ascribed to the acquisition of a more efficient initiation timing in motor
      programming. In a complex fencing gesture, the higher maximum speed of touche
      following intensive practice is discussed with regard to the inhibition of
      negative effects linked to the "refractory period" associated with the initiation
      of two closely spaced motor programs.

PMID- 11315549
TI  - Lipid peroxidation in the postnatal rat brain. Formation of 4-hydroxynonenal in
      the supraventricular corpus callosum of postnatal rats.
AB  - Lipid peroxidation is known to be associated with many neurodegenerative diseases
      and with traumatic brain injury, but its occurrence in the normal developing
      brain has not been reported. The present study was carried out using a specific
      antibody that recognises proteins modified by the end-product of lipid peroxide
      decomposition, 4-hydroxynonenal (HNE), to evaluate evaluate possible lipid
      peroxidation products in the brains of developing rats by immunocytochemistry and
      electron microscopy. Moderately dense labelling was observed in the
      supraventricular corpus callosum in the 7- and 8-day-old rats, whilst very dense
      labelling was observed in the same region, in the 9- and 10-day-old rats. Very
      little immunoreactivity was observed at 14 days, and no staining was observed in
      the corpus callosum in adult rats. HNE staining was not observed in neuronal cell
      bodies that give rise to callosal axons in the overlying cerebral cortex.
      Electron microscopy showed dense HNE staining on the basal laminae of blood
      vessels and on the plasma membranes of unmyelinated axons. Large numbers of
      rounded cells with features of oligodendrocyte precursor cells were labelled by
      Perl's stain in the supraventricular corpus callosum at postnatal day 7 and
      postnatal day 10, i.e. at times corresponding to high levels of HNE
      immunoreactivity. In contrast, very few such cells were observed in the adult
      brain, corresponding to the very little or no Perl's staining in the adult. These
      results suggest that lipid peroxidation observed in the supraventricular corpus
      callosum at postnatal day 10 could result from an accumulation of iron in this
      region, at this time.

PMID- 11315550
TI  - Involvement of GABA in medullary raphe-evoked modulation of neuronal activity in
      the periaqueductal grey matter in the rat.
AB  - Experiments were carried out in urethane-anaesthetised rats to investigate
      whether GABA is involved in mediating inhibition of neuronal activity in the
      dorsal half of the periaqueductal grey matter (PAG) after stimulation of the
      serotonin-containing projection to the PAG from nucleus raphe obscurus (NRO).
      Multibarrelled micropipettes were used to make recordings from 42 neurones in the
      dorsal half of the PAG. Most (n = 36) cells were quiescent. Their firing rate was
      therefore raised to 10-16 Hz by continuous iontophoretic application of DL
      homocysteic acid (DLH) in order to facilitate the study of inhibitory events.
      Iontophoretic application of GABA (0-10 nA) silenced every neurone tested (n =
      42), and the effect was blocked by the GABAA antagonist bicuculline (BIC, 10-20
      nA; 15/15 cells). BIC also produced an increase in ongoing activity in 14 of 15
      cells, indicating the presence of inhibitory GABAergic tone. Iontophoretically
      applied serotonin (5-HT; 10-70 nA) also inhibited ongoing activity in 9 of 11
      cells. The effect of 5-HT was not blocked by BIC. In six of seven cells,
      microinjection of 100-200 nl DLH into NRO produced a 72.3 +/- 9.4% decrease in
      neuronal firing rate which was maximal 112 +/- 18 s after the start of the
      injection and lasted for a total of 313 +/- 63 s. In five of six cells, the raphe
      evoked inhibition was blocked by BIC. It is suggested that activation of the
      serotonergic projection to the PAG from NRO engages GABA-containing interneurones
      within the PAG which mediate the inhibitory effects of raphe stimulation.

PMID- 11315551
TI  - Neuropathic pain in aged rats: behavioral responses and astrocytic activation.
AB  - We used the Bennett and Xie (1988) model of chronic neuropathic pain to study the
      effect of age on thermal and tactile sensitivity and on astrocytic activation in
      the dorsal horn of the spinal cord after nerve injury. Fischer 344 FBNF1 hybrid
      rats in three age groups, 4-6, 14-16, and 24-26 months, were studied. Rats were
      either unligated (day 0, control) or the left sciatic nerve was loosely ligated
      to cause a chronic constriction injury (CCI). CCI causes a neuropathic pain
      condition characterized by tactile allodynia and thermal hyperalgesia. Rats were
      behaviorally assessed for tactile and thermal sensitivity of their ligated and
      unligated hind paws up to 35 days postligation. Rats were sacrificed before or at
      various days postligation, and activated astrocytes were identified at the L4-L5
      levels of their spinal cords by use of an antibody to glial fibrillary acid
      protein (GFAP). The number of GFAP-ir astrocytes in the dorsal horn of the spinal
      cord in the control, uninjured condition decreased with age (P < or = 0.001) but
      increased after CCI in all three age groups. After CCI, astrocytic activation in
      the cord was less robust in aged rats than in younger ones (P < or = 0.01). Not
      all the CCI rats displayed hyperalgesia to touch and to heat. Rats with an
      increased sensitivity to heat had increased levels of GFAP-ir in their cords;
      however, rats with decreased thermal sensitivity also displayed increased GFAP
      ir. Thus the presence of activated astrocytes was not correlated with a single
      behavioral manifestation of neuropathic pain.

PMID- 11315552
TI  - Saccadic disinhibition in schizophrenia patients and their first-degree
      biological relatives. A parametric study of the effects of increasing inhibitory
      load.
AB  - Several studies have reported that patients with schizophrenia and their
      relatives perform poorly on antisaccade tasks and have suggested that this
      deficit represents saccadic disinhibition. If this proposition is correct, then
      varying task parameters that specifically increase the difficulty with which
      unwanted saccades can be inhibited should exacerbate deficits. Forty-two
      schizophrenia patients, 42 of their first-degree biological relatives, 21
      psychotic affective disorder patients, and 38 nonpsychiatric comparison subjects
      were given fixation and antisaccade tasks. The introduction of distracters and
      the presence of visible fixation stimuli were parameters used to vary the
      difficulty in suppressing unwanted saccades (inhibitory load). It is known that
      the presence of a fixation stimulus at the time when a saccade must be inhibited
      results in fewer reflexive errors on antisaccade tasks. Performance on fixation
      tasks without (low load) vs with distracters (high load) and antisaccade tasks
      that had fixation stimuli still visible (low load) vs already extinguished (high
      load) at the time when the reflexive saccade must be inhibited was compared. The
      schizophrenia patients and their first-degree biological relatives showed
      evidence of increased saccadic disinhibition that was most pronounced during high
      inhibitory load conditions. These data indicate that dysfunctional inhibitory
      processes, at least in the oculomotor domain, are associated with the liability
      to schizophrenia. Results also suggest that this genetic liability may be related
      to dysfunctional prefrontal cortical areas that provide top-down inhibitory
      control over reflexive saccade generation.

PMID- 11315553
TI  - The effect of the Ebbinghaus illusion on grasping behaviour of children.
AB  - Within the context of the Ebbinghaus illusion, adults regularly misjudge the
      physical size of a centre disc, yet scale their hand aperture according to its
      actual size. Separate visual pathways for perception and action are assumed to
      account for this finding. The dorsal visual stream is said to elaborate on
      egocentric (visuomotor), while the ventral stream is involved in allocentric
      transformations (object recognition). This study examines the ontogenetic
      development of this dissociation between perception and action in 35 children
      between the ages of 5 and 12 years. We report four major results. First, when
      children judged object size without grasping the disc, their judgements were
      deceived by the illusion to the same extent as adults. However, when asked to
      estimate size and then to grasp the disc, young children's (5-7 years) perceptual
      judgements became unreliable, while adults were still reliably deceived by the
      illusion in 80% of their trials. Second, the younger the children, the more their
      aperture was affected by the illusional surround. Discs of the same size were
      grasped with a smaller aperture when surrounded by a small annulus, although they
      were perceived as being larger. Third, young children used the largest safety
      margin during grasping. Fourth, the reliance on visual feedback decreased with
      increasing age, which was documented by shorter movement times and earlier
      maximum hand opening during grasping in the older children (feedforward control).
      Our results indicate that grasping behaviour in children is subject to an
      interaction between ventral and dorsal processes. Both pathways seem not to be
      functionally segregated in early and middle childhood. The data are inconclusive
      about whether young children predominantly use a specific visual stream for
      either a perceptual or motor task. However, our data demonstrate that children
      were relying on both visual processing streams during perceptual as well as
      visuomotor tasks. We found that children used egocentric cues to make perceptual
      judgements, while their grasping gestures were not exclusively shaped by viewer
      centred but also by object-centred information.

PMID- 11315554
TI  - The effect of expectations on hitting moving targets: influence of the preceding
      target's speed.
AB  - When hitting a target that is moving, the time for planning the interception is
      limited. Instead of waiting for all the necessary information about the target's
      position and speed before starting to move, subjects could use their previous
      experience with similar targets to make initial guesses and adjust as new
      information becomes available. In the present study we examined whether the speed
      of the preceding target influences a hitting movement. Subjects hit moving
      targets that appeared on a screen about 40 cm in front of them. The targets moved
      at 6, 12 or 18 cm/s. Both the hand's initial movement direction and the final
      hitting error depended on the speed of the preceding target. We conclude that
      people control the way they hit moving targets on the basis of the speed of the
      preceding target.

PMID- 11315555
TI  - Participation of NK1 receptors in nociceptin-induced modulation of rat knee joint
      mechanosensitivity.
AB  - Nociceptin is known to act peripherally in the rat knee joint to modulate
      articular mechanosensitivity and it has been postulated that neurokinin-1 (NK1)
      receptors may be involved in this process. To test this hypothesis, single unit
      extracellular recordings were made from knee joint primary afferents in response
      to normal and extreme rotation of the joint. Afferent firing rate was assessed
      following close intraarterial injection of the NK1 antagonist RP67580 followed by
      administration of 20 nmol nociceptin. With both normal and hyper-rotation of the
      knee, nociceptin was unable to elicit its usual mechanomodulatory effect such
      that afferent activity was not significantly different from control (P = 0.7572
      and P = 0.9182 for normal and hyper-rotation of the joint, respectively). These
      data indicate that nociceptin-induced mechanosensitivity changes in the rat knee
      depend upon NK1 receptor activation possibly through secondary release of
      substance P.

PMID- 11315556
TI  - Motor adaptation to an optical illusion.
AB  - This research investigated the effects of an orientation illusion on action, as
      well as the ability of the motor system to adapt to the illusion. Subjects
      reached out and picked up a small bar placed at various orientations. A
      background grating was used to induce an orientation illusion. When the direction
      of the illusion was reversed, the following seven trials revealed a large
      illusion effect in the early portion of the reach. In the subsequent seven
      trials, no effect of the illusion was present. This pattern of adaptation was
      similar to the pattern often obtained with displacing prisms, suggesting that the
      two types of visual distortions present the motor system with similar challenges
      that it meets in similar ways. These findings are consistent with a
      planning/control model that argues for separate visual representations underlying
      the planning and on-line control of reaching.

PMID- 11315557
TI  - Adenosylmethionine-dependent iron-sulfur enzymes: versatile clusters in a radical
      new role.
AB  - Iron-sulfur clusters are widespread in biological systems and participate in a
      broad range of functions. These functions include electron transport, mediation
      of redox as well as non-redox catalysis, and regulation of gene expression. A new
      role for iron-sulfur clusters has emerged in recent years as a number of enzymes
      have been identified that utilize Fe-S clusters and S-adenosylmethionine (AdoMet)
      to initiate radical catalysis. This Fe-S cluster-mediated radical catalysis
      includes the generation of stable protein-centered radicals as well as generation
      of substrate radical intermediates, with evidence suggesting a common mechanism
      involving an intermediate adenosyl radical. Although the mechanism of generation
      of the adenosyl radical intermediate is currently not well understood, it likely
      represents novel chemistry for iron-sulfur clusters. The purpose of this review
      is to present the current state of knowledge of this newly emerging group of Fe
      S/AdoMet enzymes.

PMID- 11315558
TI  - Direct electrochemical characterization of hyperthermophilic Thermococcus celer
      metalloenzymes involved in hydrogen production from pyruvate.
AB  - The reduction potentials of the metalloproteins pyruvate ferredoxin
      oxidoreductase (POR), ferredoxin, and hydrogenase isolated from hyperthermophilic
      Thermococcus celer (Topt = 88 degrees C) were determined as a function of
      temperature from 10 to 85 degrees C. Square-wave voltammetry experiments were
      carried out on 15 microL samples directly at an unmodified "edge-polished"
      pyrolytic graphite electrode using MgCl2 as an electrode promoter. POR exhibited
      two voltammetric waves with peaks at -280 and -403 mV at room temperature,
      indicating multiple redox centers, and a single wave at -420 mV at 85 degrees C.
      These waves displayed different temperature-dependent peak positions and peak
      heights, indicating that these redox centers have different thermodynamic and
      kinetic properties. Ferredoxin displayed a single linear temperature-dependent
      voltammetric wave at -280 mV at room temperature and -327 mV at 85 degrees C.
      Hydrogenase displayed a single biphasic temperature-dependent voltammetric wave
      at -197 mV at room temperature and -211 mV at 85 degrees C. Thermodynamic
      parameters associated with electron transfer, namely standard enthalpies and
      entropies for the redox centers in the various proteins, are reported.

PMID- 11315559
TI  - Comparison and characterization of the [Fe4S4]2+/3+ centre in the wild-type and
      C77S mutated HiPIPs from Chromatium vinosum monitored by Mossbauer, 57Fe ENDOR
      and EPR spectroscopies.
AB  - Mossbauer, 57Fe ENDOR, CW and pulsed EPR experiments were performed on the
      reduced and the oxidized high-potential iron proteins (HiPIPs) of the wild type
      (WT) and the C77S mutant from Chromatium vinosum. The EPR spectra of the oxidized
      WT and mutant show three species respectively having nearly the same g-values but
      strongly changed spectral contributions. Relaxation times were estimated for
      oxidized WT and mutant at T = 5 K with pulsed EPR. A-tensor components of both
      iron pairs were obtained by 57Fe ENDOR, proving a similar magnetic structure for
      the WT and the mutant. Electronic relaxation has to be taken into account at T =
      5 K in native and mutated oxidized HiPIPs to achieve agreement between Mossbauer
      and 57Fe ENDOR spectroscopies. The Mossbauer spectroscopy shows that the oxidized
      cluster contains a pure ferric and a mixed-valence iron pair coupled
      antiparallel. While all cluster irons from reduced C. vinosum WT are
      indistinguishable in the Mossbauer spectrum, the reduced C77S mutant shows a non
      equivalence between the serine-bound and the three cysteine-ligated iron ions.
      The Mossbauer parameters confirm a loss of the covalent character of the iron
      bond when S is replaced by O and indicate a shift of the cluster's electron cloud
      towards the serine. Mossbauer spectra of the oxidized mutant can be simulated
      with two models: model I introduces a single electronic isomer with the serine
      always ligated to a ferric iron. Model II assumes two equally populated
      electronic isomers with the serine ligated to a ferric iron and a mixed-valence
      iron, respectively. The latter model is in better agreement with EPR and NMR.

PMID- 11315560
TI  - Lipari-Szabo approach as a tool for the analysis of macromolecular
      gadolinium(III)-based MRI contrast agents illustrated by the [Gd(EGTA-BA
      (CH2)12)]nn+ polymer.
AB  - The parameters governing the water proton relaxivity of the [Gd(EGTA-BA
      (CH2)12)]nn+ polymeric complex were determined through global analysis of 17O
      NMR, EPR and nuclear magnetic relaxation dispersion (NMRD) data [EGTA-BA2- = 3,12
      bis(carbamoylmethyl)- 6,9-dioxa-3,12-diazatetradecanedioate(2-)]. The Lipari
      Szabo approach that distinguishes the global motion of the polymer (tau g) from
      the local motion of the Gd(III)-water vector (tau l) was necessary to describe
      the 1H and 17O longitudinal relaxation rates; therefore for the first time it was
      included in the global simultaneous analysis of the EPR, 17O NMR and NMRD data.
      The polymer consists on average of only five monomeric units, which limits the
      intramolecular hydrophobic interactions operating between the (CH2)12 groups.
      Hence the global rotational correlation time is not very high (tau g298 = 3880 +/
      750 ps) compared to the corresponding DTPA-BA-based polymer (about 15 monomeric
      units), where tau g298 = 6500 ps. As a consequence, the relaxivity is limited by
      the rotation, which precludes the advantage obtained from the fast exchanging
      chelating unit (kex298 = 2.2 +/- 0.1 x 10(6) s-1).

PMID- 11315561
TI  - Development of novel mixed-ligand oxotechnetium [SNS/S] complexes as potential 5
      HT1A receptor imaging agents.
AB  - The "3 + 1" ligand system [SN(R)S/S combination] was applied in order to
      synthesize neutral mixed-ligand oxotechnetium complexes of the general formula
      99mTcO[SN(R)S]/[S] as potential 5-HT1A receptor imaging agents. The complexes are
      carrying the 1-(2-methoxyphenyl)piperazine moiety, a fragment of the true 5-HT1A
      antagonist WAY 100635, either on the monodentate ligand [S] or on the tridentate
      ligand [SN(R)S]. The complexes MO[EtN(CH2CH2S)2] [o-MeOC6H4N(CH2CH2)2NCH2CH2S]
      (3), MO[o- MeOC6H4N(CH2CH2)2N(CH2)3N(CH2CH2S)2][PhS] (6) and MO[o
      MeOC6H4N(CH2CH2)2N(CH2)3N(CH2CH2S)2] [PhCH2CH2S] (9), where M = 99mTc, were
      prepared at tracer level using 99mTc glucoheptonate as precursor. For structural
      characterization, the analogous oxorhenium (M = Re, 1, 4 and 7, respectively) and
      oxotechnetium (M = 99gTc, 2, 5 and 8, respectively) complexes were prepared by
      ligand exchange reactions. All products were characterized by elemental analysis
      and spectroscopic methods. Complexes 1, 4 and 7 were further characterized by
      crystallographic analysis. For 1, the coordination geometry about rhenium can be
      described as trigonally distorted square pyramidal (tau = 0.36), while for 4 and
      7, as distorted trigonal bipyramidal (tau = 0.66 and tau = 0.61, respectively).
      The coordination sphere about oxorhenium in all complexes is defined by the SNS
      donor atom set of the tridentate ligand and the sulfur atom of the monodentate
      coligand. The structure of the 99mTc complexes 3, 6 and 9 was established by
      comparative HPLC using authentic oxorhenium and oxotechnetium samples. The
      binding affinity of oxorhenium compounds for the 5-HT1A receptor subtype was
      determined in rat brain hippocampal preparations (IC50 = 6-31 nM). Preliminary
      tissue distribution data in healthy mice revealed the ability of all three 99mTc
      complexes to cross the intact blood-brain barrier (0.49-1.15% ID at 1 min p.i.).
      In addition, complexes 6 and 9 showed significant brain retention. These
      promising results have demonstrated that the SNS/S mixed-ligand system can be
      used in the development of 99mTc complexes as potential 5-HT1A receptor imaging
      agents.

PMID- 11315562
TI  - Elucidation of a [4Fe-4S] cluster degradation pathway: rapid kinetic studies of
      the degradation of Chromatium vinosum HiPIP.
AB  - Irreversible disassembly of the 4Fe-4S cluster in Chromatium vinosum high
      potential iron protein (HiPIP) has been investigated in the presence of a low
      concentration of guanidinium hydrochloride. From the dependence of degradation
      rate on [H+], it is deduced that at least three protons are required to trigger
      efficient cluster degradation. Under these conditions the protonated cluster
      shows broadened Mossbauer signals, but delta EQ (1.1 mm/s) and delta (0.44 mm/s)
      are similar to the native form. Collapse of the protonated transition state
      complex, revealed by rapid-quench Mossbauer experiments, occurs with a measured
      rate constant kobs approximately 0.72 +/- 0.35 s-1 that is consistent with
      results from time-resolved electronic absorption and fluorescence (kobs
      approximately 0.4 +/- 0.1 s-1) and EPR (kobs approximately 0.62 +/- 0.18 s-1)
      measurements. Apparently, guanidinium hydrochloride serves to perturb the
      tertiary structure of the protein, facilitating protonation of the cluster, but
      not degradation per se. Release of iron ions occurs even more slowly with kobs
      approximately 0.07 +/- 0.02 s-1, as determined by the appearance of the g = 4.3
      EPR signal. Proton-mediated cluster degradation is sensitive to the oxidation
      state of the cluster, with the oxidized state showing a two-fold slower rate in
      acidic solutions as a result of increased electrostatic repulsion with the
      cluster. Consistent results are obtained from absorption, fluorescence, Mossbauer
      and EPR measurements.

PMID- 11315563
TI  - A nonheme iron(II) complex that models the redox cycle of lipoxygenase.
AB  - The air-stable complex [Fe(6-Me3-TPA) (O2CAr)]+ [1; 6-Me3-TPA = tris(6-methyl-2
      pyridylmethyl)amine] has been synthesized as a model for the iron(II) site of
      lipoxygenase. This iron(II) complex reacts with 0.5 equiv ROOH to form a yellow
      species, which has been formulated as [FeIII(OH)(6-Me3-TPA) (O2CAr)]+ (2) by
      electrospray mass spectrometry. Addition of more ROOH converts 2 into a purple
      species, which is characterized by electrospray ionization mass spectrometry and
      resonance Raman spectroscopy as [FeIII(OOR)(6-Me3-TPA)(O2CAr)]+. The purple
      species is metastable and decomposes via Fe-O bond homolysis to regenerate the
      starting iron(II) complex. These metal-centered transformations parallel the
      changes observed for lipoxygenase in its reaction with its product hydroperoxide.

PMID- 11315564
TI  - Electron self-exchange kinetics in two average-valence dicopper cryptates.
AB  - Electron self-exchange rates, reported for two average-valence dicopper cryptates
      are, at around 10(5) M-1 s-1, at the high end of the range for small-molecule
      model compounds. The cross-exchange reaction rate, and those for oxidation with
      [Co(ox)3]3-, are consistent with an outer-sphere reaction mechanism. Despite the
      necessity for copper-copper bond making and breaking in the course of redox for
      one of the cryptates, the self-exchange rate is not decreased relative to the
      other cryptate, showing that this step is not rate limiting.

PMID- 11315565
TI  - Hydrolysis of the tumor-inhibiting ruthenium(III) complexes HIm trans
      [RuCl4(im)2] and HInd trans-[RuCl4(ind)2] investigated by means of HPCE and HPLC
      MS.
AB  - High performance capillary electrophoresis (HPCE) as well as high performance
      liquid chromatography-mass spectrometry (HPLC-MS) have been applied to the
      separation, identification and quantification of the tumor-inhibiting ruthenium
      compounds HIm trans-[RuCl4(im)2] (im = imidazole) and HInd trans-[RuCl4(ind)2]
      (ind = indazole) and their hydrolysis products. The half-lives for the hydrolytic
      decomposition of the Ru(III) compounds were determined by monitoring the relative
      decrease of the original complex anion under different conditions by means of
      capillary electrophoresis. The decomposition follows pseudo-first-order kinetics.
      The rate constants in water at 25 degrees C are 1.102 +/- 0.091 x 10(-5) s-1 for
      HIm trans-[RuCl4(im)2] and 0.395 +/- 0.014 x 10(-5) s-1 for HInd trans
      [RuCl4(ind)2]. About 8% of HIm trans-[RuCl4(im)2] but only about 2% of HInd trans
      [RuCl4(ind)2] were hydrolyzed after 1 h at room temperature. Whereas the
      hydrolysis rate of the imidazole complex is independent of the pH value, the
      indazole complex hydrolyzes much faster at higher pH. The half-life of HInd trans
      [RuCl4(ind)2] in phosphate buffer at pH 6.0 and 37 degrees C is 5.4 h, whereas it
      is less than 0.5 h at pH 7.4. In contrast to the imidazole complex, where no
      dependence on the buffer system was observed, hydrolysis of the indazole complex
      is even faster if a buffer containing hydrogen carbonate is used. The formation
      of [RuCl2(H2O)2(im)2]+ could be demonstrated by HPLC-MS measurements. In the case
      of the indazole complex, a release of the indazole ligands results in the
      formation of [RuCl4(H2O)2]-.

PMID- 11315566
TI  - Structure-based computational study of the catalytic and inhibition mechanisms of
      urease.
AB  - The viability of different mechanisms of catalysis and inhibition of the nickel
      containing enzyme urease was explored using the available high-resolution
      structures of the enzyme isolated from Bacillus pasteurii in the native form and
      inhibited with several substrates. The structures and charge distribution of
      urea, its catalytic transition state, and three enzyme inhibitors were calculated
      using ab initio and density functional theory methods. The DOCK program suite was
      employed to determine families of structures of urease complexes characterized by
      docking energy scores indicative of their relative stability according to steric
      and electrostatic criteria. Adjustment of the parameters used by DOCK, in order
      to account for the presence of the metal ion in the active site, resulted in the
      calculation of best energy structures for the nickel-bound inhibitors beta
      mercaptoethanol, acetohydroxamic acid, and diamidophosphoric acid. These
      calculated structures are in good agreement with the experimentally determined
      structures, and provide hints on the reactivity and mobility of the inhibitors in
      the active site. The same docking protocol was applied to the substrate urea and
      its catalytic transition state, in order to shed light onto the possible
      catalytic steps occurring at the binuclear nickel active site. These calculations
      suggest that the most viable pathway for urea hydrolysis involve a nucleophilic
      attack by the bridging, and not the terminal, nickel-bound hydroxide onto a urea
      molecule, with active site residues playing important roles in orienting and
      activating the substrate, and stabilizing the catalytic transition state.

PMID- 11315567
TI  - Crystal structures of oxidized dinuclear manganese centres in Mn-substituted
      class I ribonucleotide reductase from Escherichia coli: carboxylate shifts with
      implications for O2 activation and radical generation.
AB  - The di-iron carboxylate proteins constitute a diverse class of non-heme iron
      enzymes performing a multitude of redox reactions. These reactions usually
      involve high-valent Fe-oxo species and are thought to be controlled by
      carboxylate shifts. Owing to their short lifetime, the intermediate structures
      have so far escaped structural characterization by X-ray crystallography. In an
      attempt to map the carboxylate conformations available to the protein during
      different redox states and different ligand environments, we have studied metal
      substituted forms of the R2 protein of ribonucleotide reductase from Escherichia
      coli. In the present work we have solved the crystal structures of Mn-substituted
      R2 oxidized in two different ways. Oxidation was performed using either nitric
      oxide or a combination of hydrogen peroxide and hydroxylamine. The two structures
      are virtually identical, indicating that the oxidation states are the same, most
      likely a mixed-valent MnII-MnIII centre. One of the carboxylate ligands (D84)
      adopts a new, so far unseen, conformation, which could participate in the
      mechanism for radical generation in R2. E238 adopts a bridging-chelating
      conformation proposed to be important for proper O2 activation but not previously
      observed in the wild-type enzyme. Probable catalase activity was also observed
      during the oxidation with H2O2, indicating mechanistic similarities to the di-Mn
      catalases.

PMID- 11315568
TI  - Crystal structure of low-potential cytochrome c549 from Synechocystis sp. PCC
      6803 at 1.21 A resolution.
AB  - The crystal structure of low-potential cytochrome c549, an extrinsic component of
      the photosystem II (PS II) from Synechocystis sp. PCC 6803, was obtained directly
      from single-wavelength 1.21 A resolution diffraction data. This is the first
      monodomain bis-histidinyl monoheme cytochrome c to be structurally characterized.
      The extended N-terminal region of c549 builds up a two-strand antiparallel beta
      sheet in a hairpin motif, which extends through two molecules owing to crystal
      packing. Both peptide termini are involved in crystal contacts, which may explain
      their protrusion out of the globular fold. The C-terminus is preceded by a 9 A
      long hydrophobic finger extending from a positively charged base and could be
      involved in PSII interactions, as well as a protruding negative patch built by a
      set of conserved acidic residues among c549 sequences.

PMID- 11315569
TI  - Metabolic, enzymatic and endocrine status in high-yielding dairy cows--Part 2.
AB  - Pairs of 29 high-yielding (HC) dairy cows (> or = 45 kg/day reached at least once
      during lactation) and 29 corresponding control (CC) cows (with milk yields
      representing the average yield of the herds) were studied in 29 Swiss farms from
      March 1995 to September 1996. The hypothesis tested was that there are
      differences in metabolic, enzymatic and endocrine status between HC and CC cows.
      Cows were studied 2 weeks before and at 5, 9, 13, 17 and 40 weeks post-partum.
      Concentrations of metabolites, minerals and hormones and enzyme activities were
      in the normal range in both HC and CC cows. Changes in metabolic and endocrine
      traits in early lactation expressed insufficient energy intake, but were similar
      in both HC and CC cows. Homeorhetic and homeostatic control of metabolism in HC
      cows was thus adequate to adjust to and allow high milk yields. Under adequate
      husbandry, management and feeding conditions, metabolic disease problems in HC
      cows [10,500 kg energy-corrected milk (ECM)/lactation, peak yields of > or = 45
      kg ECM/day] can be avoided.

PMID- 11315570
TI  - Evaluation of haloperidol--ketamine mixture (1:1) anaesthesia in dogs.
AB  - Four clinically healthy dogs of either sex, aged 3-5 years, weighing between 9
      and 18 kg and maintained under uniform management conditions, were administered
      haloperidol (5 mg/ml) and ketamine (50 mg/ml) intravenously in 1:1 ratio until
      the pedal reflex was lost. The calculated doses of haloperidol and ketamine were
      1.71 and 17.05 mg/kg body weight intravenously, respectively. Corneal and
      palpebral reflexes were maintained although pain reflexes were absent up to 20
      min of the cocktail administration. The induction of anaesthesia was quick and
      smooth. There was moderate to good muscle relaxation and analgesia. Mean arterial
      and central venous pressures and tidal volume decreased significantly (P < 0.05)
      from baseline values. Significant tachycardia and hyperglycemia were observed.

PMID- 11315571
TI  - Statistical shape analysis of volumetric capnograms: evaluation of a new approach
      for the assessment of pulmonary function in horses with chronic obstructive
      pulmonary disease.
AB  - The shape of the volumetric capnogram is modified by airway obstruction, and the
      evaluation of this deformation could allow an indirect measurement of bronchial
      patency. The study included 35 horses; five horses without evidence of pulmonary
      disease (group I) and 30 horses suffering from different degrees of chronic
      obstructive pulmonary disease (COPD) (groups II-IV). Data of recorded CO2 and
      volume curves were off-line plotted and statistically analysed using regression
      analysis. Analyses were performed separately for fractions 25-95% (VTE25-95), 25
      50% (VTE25-50) and 50-95% (VTE50-95) of expiratory tidal volume. For VTE25-95
      estimates of linear and quadratic regression parameters were significantly
      different between groups. For VTE25-50 linear terms were significant in all
      clinical groups and decreased considerably from group I to group IV. Linear and
      quadratic terms for VTE50-95 were significant in all clinical groups and
      increased with the severity of COPD. The difference of total expiratory CO2
      volume was significant between all groups. Statistical analysis of the volumetric
      capnogram is a precise method for description of shape deformities of the single
      breath diagram for CO2 (SBD-CO2) in horses with COPD and global models including
      phase II and III of the SBD-CO2 are helpful in the detection of pulmonary
      function impairment. However, although the model of the statistical shape
      analysis of the SBD-CO2 is precise, it may not necessarily be a useful test to
      discriminate horses with minor, moderate and severe COPD for clinical use.

PMID- 11315572
TI  - Adjuvant post-operative chemotherapy in bitches with mammary cancer.
AB  - The survival time in a group of eight bitches with malignant mammary tumours
      given adjuvant post-operative chemotherapy was compared with survival in another
      group of eight bitches with mammary cancer which were treated by surgical
      excision alone. The same surgical procedure was used in both groups. All bitches
      had stage III disease according to the World Health Organization clinical staging
      system. Histologically, 10 of the bitches had complex carcinomas (carcinomatous
      mixed tumours), the remaining six bitches had carcinosarcomas. The
      chemotherapeutic protocol used was a combination of 5-fluorouracil (150 mg/m2 of
      body surface area) and cyclophosphamide (100 mg/m2) given on the same day,
      intravenously, every week for four consecutive weeks. Chemotherapy was started
      one week post-surgery. Selected haematological parameters (packed cell volume,
      white blood cell count, platelet count and differential white blood cell count)
      and serum biochemical parameters (alanine aminotransferase, alkaline phosphatase,
      blood urea nitrogen and creatinine) were measured before and during chemotherapy.
      Survival analysis indicated that the chemotherapeutic regimen had a positive
      influence on the disease-free interval and the survival time of the eight bitches
      (P < 0.05). Although leucocyte numbers were significantly decreased (P < 0.001)
      during chemotherapy, the mean leucocyte counts remained within normal limits.
      Temporary leukopenia was noted only in one bitch. Packed cell volume and alkaline
      phosphatase increased significantly (P < 0.05) but within normal limits.
      Creatinine was also increased significantly (P < 0.01) but the mean creatinine
      concentrations were within normal limits, although in half of the bitches the
      concentrations occasionally rose above normal.

PMID- 11315573
TI  - Milk yield and composition, nutrition, body conformation traits, body condition
      scores, fertility and diseases in high-yielding dairy cows--Part 1.
AB  - Twenty-nine pairs of high-yielding dairy cows (HC; > or = 45 kg/day reached at
      least once during lactation) and corresponding control cows (CC; with milk yields
      representing the average yield of the herds) were examined on 29 Swiss farms from
      March 1995 to September 1996. The hypotheses were tested that there are
      differences in feed intake, body-conformation traits, body weight (BW), body
      condition score (BCS), fertility status and disease incidence between HC and CC
      cows. Cows were studied 2 weeks before and at 5, 9, 13, 17 and 40 weeks post
      partum. HC cows produced more energy-corrected milk (ECM) than CC cows (10,670 +/
      321 kg in 293 +/- 5 days and 8385 +/- 283 kg in 294 +/- 4 days, respectively; P
      < or = 0.001) and yields in the first 100 days of lactation were greater in HC
      than in CC cows (46.2 +/- 1.1 and 36.2 +/- 1.0 kg ECM/day, respectively; P < or =
      0.001). Concentrate intake was greater (P < or = 0.05) in HC than in CC cows (7.6
      +/- 0.5 and 5.7 +/- 0.5 kg/day, respectively) and dry matter intakes (measured in
      week 5 of lactation over 3 days on six farms) were greater in HC than in CC cows
      (24.0 +/- 1.1 and 20.3 +/- 1.1 kg/day, respectively; P < or = 0.001). HC cows
      were taller than CC cows (wither heights 143.3 +/- 0.8 and 140.1 +/- 0.8 cm,
      respectively; P < or = 0.01). Although BW in HC cows was greater than in CC cows
      throughout the study, differences and decreases of BW during lactation were not
      significant. BCS at the end of pregnancy and decrements during lactation were
      similar in HC and CC cows. Fertility parameters were similar in HC and CC cows.
      Incidences of mastitis, claw and feet problems, hypocalcemia/downer cow syndrome,
      ovarian cysts and abortions were similar in HC and CC cows, but there were more
      indigestion problems in HC than in CC cows.

PMID- 11315574
TI  - [Treatment of stent restenosis using rotational atherectomy: mechanisms and
      results].
AB  - Restenosis after coronary stent implantation remains one of the major limitations
      of this treatment modality. At present, redilatation is considered the
      therapeutic option of choice for focal lesions; however, long restenotic lesions
      (> 10 mm) do not respond favourably. Despite the emerging concept of
      intracoronary radiation, encouraging acute procedural results are also reported
      for different debulking techniques (excimer laser angioplasty, directional
      coronary atherectomy, and rotational atherectomy, or rotablation). Rotablation
      has been studied most extensively with acute and long-term results published in a
      total of 500 patients. Experimental and first clinical data indicate favourable
      results for the rotablator as compared to balloon angioplasty alone for the
      treatment of in-stent restenosis. Data from the first two randomised clinical
      trials (ROSTER and A.R.T.I.S.T. trials) have now been published in abstract form,
      with conflicting results: whereas the monocenter ROSTER trial suggests a clinical
      benefit to patients treated by the rotablator, the multicenter A.R.T.I.S.T. trial
      including nearly 300 patients could not prove a benefit for the rotablator as
      compared to re-dilatation in patients with diffuse stent restenosis. Currently,
      rotablation for the treatment of restenosis can not be considered as the first
      line treatment modality in patients with stent restenosis. As a result of
      unsatisfying angiographic and clinical long-term results by the use of a variety
      of treatment modalities in diffuse stent restenosis, prevention of this
      iatrogenic entity will become mandatory.

PMID- 11315575
TI  - [P-wave signal averaging-ECG: normal values and reproducibility].
AB  - Signal averaging techniques are used for detection of low amplitude, high
      frequency signals in the surface ECG. P-wave signal-averaging has been used to
      predict the risk for development of atrial tachyarrhythmias in patients with
      structural heart disease. There is, however, a lack of prospective studies
      evaluating normal values of the P-wave signal-averaged ECG in healthy
      individuals. Moreover, day-to-day reproducibility of results of P-wave signal
      averaging is not precisely known. Thus, the aim of this study was to determine
      normal values and reproducibility of time-domain P-wave signal-averaging in a
      large cohort of healthy volunteers. A commercially available device (MAC 5000,
      Marquette Hellige) was used for signal-averaging. A vector magnitude was
      calculated from Frank's orthogonal leads after P-waves were sampled and filtered
      with a spectral filter using fast fourier transform. We examined 123 volunteers
      without cardiovascular disease at two occasions. Mean P-wave duration was 114 +/-
      13 ms for the overall study population. There was a slight but statistically
      significant increase in filtered P-wave duration with age (r = 0.32, p < 0.001).
      All values were reliably reproducible upon the second examination (r = 0.624 to
      0.706, p < 0.0001). These results may serve as a future reference to other
      studies examining patients with structural heart disease.

PMID- 11315576
TI  - [Predictive value of frequency, duration and rate of ventricular salvos in
      ambulatory ECG for inducibility of sustained ventricular tachycardia].
AB  - Identification of high risk patients with coronary artery disease (CAD) prone to
      sudden cardiac death still remains a difficult issue. In 211 patients with CAD
      diagnosed by coronary angiography and documented non-sustained ventricular
      tachycardia (NSVT), programmed ventricular stimulation (PVS) was performed. NSVTs
      documented during Holter monitoring were analysed concerning frequency, duration
      and rate. To relate those parameters to the inducibility of sustained monomorphic
      ventricular tachycardias (MVT) during PVS, the total population was divided in
      different groups; patients with 1, 2-5 or > 5 salvos within 24 h; patients having
      salvos with a rate of > or = 150/min or < 150/min; patients with 3-5, 6-10 or >
      10 consecutive extra beats. It could be demonstrated that in patients with CAD
      and NSVTs, induction of MVTs during PVS is more likely if the rate of the
      spontaneously occurring NSVT is > or = 150/min (22.1 vs 8.9%; p = 0.042). In
      contrast, there is apparently no correlation between the duration and incidence
      of NSVTs and the prevalence of MVTs during PVS. Multivariate analysis revealed
      the rate of documented NSVTs (odds ratio 2.98, p = 0.0314) and a decrease of left
      ventricular ejection fraction (odds ratio 1.69; p = 0.0013) as independent risk
      factors for the inducibility of MVTs. Conclusions CAD patients with fast salvos
      (> or = 150 beats/min) and reduced left ventricular ejection fraction are more
      likely to reveal inducible MVT during PVS and should, therefore, preferably be
      subjected to invasive risk stratification. The number of salvos per day and the
      number of consecutive beats, on the other hand, do not seem to be of relevant
      predictive value.

PMID- 11315577
TI  - [Electrocardiographic signs of autonomic imbalance in infants with congenital
      heart defects].
AB  - Infants with congenital heart disease (CHD) and heart failure have elevated
      plasma norepinephrine levels (NE) as a sign for sympathetic activation. We
      analysed ECGs of 64 infants with CHD and found normal heart rates on average in
      four groups split up according to their NE. Mean heart rate in Holter ECGs was
      significantly reduced in infants with low NE (below 350 ng/l) but normal in the
      other groups (NE < 350 ng/l: 121 +/- 10/min; NE = 350-700 ng/l: 139 +/- 11/min;
      NE = 700-1300 ng/l: 142 +/- 13/min; NE > 1300 ng/l: 135 +/- 12/min). An analysis
      of heart rate variability in a subgroup of 25 infants showed significantly
      reduced values in patients with elevated NE in comparison to 70 healthy infants.
      Significantly reduced frequency domain measures in infants with elevated NE but
      also normal NE are evidence for a high diagnostic sensitivity of an analysis of
      heart rate variability for autonomic imbalance with sympathetic activation and
      parasympathetic withdrawal in infants with CHD.

PMID- 11315578
TI  - [Thrombolysis of prosthetic heart valve thrombosis using recombinant tissue
      plasminogen activator (rt-PA) in infancy and childhood].
AB  - Thrombotic obstruction of a mechanical cardiac valve prosthesis requires urgent
      therapy. We report on the treatment of prosthetic valve thrombosis with
      recombinant tissue plasminogen activator (rt-PA) in three children at the age of
      4, 10 and 18 months, in whom a St. Jude Medical prosthesis had been placed at the
      atrioventricular valve level 2 to 6 weeks earlier. The initial rt-PA dose was 0.4
      mg/kg given over 15 min and followed by a continuous daily infusion of 1.6 to 2.0
      mg/kg. In addition the patients received heparin (200 U/kg/d). Thrombolytic
      therapy was administered for a range of 4 to 28 days. The therapy was successful
      in the first case. The second child had four recurrent events of prosthetic valve
      thrombosis and the thrombolytic therapy was successful three times. However, the
      prosthesis had to be finally replaced. In the third case the thrombolytic therapy
      was only partially successful due to an organized thrombus requiring prosthesis
      replacement.

PMID- 11315579
TI  - [Secondary immunologically-caused myocarditis, pericarditis and exudative
      pleuritis due to meningococcal meningitis].
AB  - Myocarditis, pericarditis and pleural effusion as secondary immunological
      reactions due to meningococcal meningitis are rare. Meningococcal meningitis is
      itself uncommon, with a morbidity of approximately 1.25 cases per 100,000
      inhabitants per year in Germany. Cardial participation could be observed either
      primary infectious-toxic in the first week or secondary immunologic in the second
      week after disease onset. In our patient, six days after the onset of
      meningococcal meningitis (serogroup B) a distinct swelling of the myocardium
      appeared together with pericardial effusion in the absence of Waterhouse
      Friderichsen syndrome. This case is proving difficult to tackle therapeutically
      due to repeated relapses.

PMID- 11315580
TI  - Fatal myocardial infarction in a young man caused by a right megadolicho-coronary
      artery with thrombosis: a case report.
AB  - A case of fatal myocardial infarction in a young man, secondary to thrombosis of
      an isolated ectatic coronary artery, is reported. Histological study of this
      abnormal artery demonstrated that it was of elastic type in its proximal two
      centimeters. This abnormal arterial structure supports the hypothesis of a
      congenital defect.

PMID- 11315581
TI  - [The role of magnetic resonance imaging in the diagnosis of coronary disease].
AB  - As the number of diagnostic coronary angiographies without subsequent
      revascularization procedures is continuously rising, the need for non-invasive
      diagnostic procedures with a high diagnostic accuracy is well appreciated.
      Because of the technical advances in magnetic resonance imaging (MRI) over the
      last few years, major improvements have been made in the functional assessment of
      wall motion, myocardial perfusion and coronary flow measurements, as well as the
      visualization of the anatomy of the coronary arteries by MRI. Besides these
      classical parameters of ischemia and anatomical pathology, for the first time MRI
      might offer the possibility to not only non-invasively assess the lumen of the
      coronary arteries, but also to visualize the vessel wall. Thus, early
      manifestations of coronary artery disease may be detectable for the
      identification of patients with preclinical disease as candidates for aggressive
      risk modification. In this review the current status as well as future
      perspectives of MRI are discussed.

PMID- 11315582
TI  - [Guidelines for the treatment of chronic heart failure. Issued by the Executive
      Committee of the German Society of Cardiology--Heart and Circulation Research,
      compiled on behalf of the Commission of Clinical Cardiology in cooperation with
      Pharmaceutic Commission of the German Physicians' Association].

PMID- 11315583
TI  - [Nerve-sparing radical retropubic prostatectomy. Results of a patient survey].
AB  - Improved selection criteria have led to an increasing number of nerve-sparing
      radical retropubic prostatectomies (RRP) in patients with clinically localized
      prostate cancer. The results based on patient questionnaires regarding
      postoperative erectile function are described. Between January 1992 and March
      1999, 366 patients (mean age: 62.5 years) underwent uni- or bilateral nerve
      sparing RRP at our institution. For evaluation of postoperative patient-reported
      rates of sexual and erectile function, a questionnaire was used after a follow-up
      of at least 12 months. Data of five operation periods were analyzed. The results
      of the unilateral procedure for the five operation periods revealed consistent
      rates of 13-29% for erections sufficient for intercourse. Bilateral nerve-sparing
      procedures were almost exclusively performed in periods 3 to 5; only four
      patients from period 2 underwent the bilateral procedure. The rates of
      intercourse-sufficient erections were 25% (period 2), 61% (period 3), 50% (period
      4), and 52% (period 5), respectively. The results of the unilateral procedure
      were disappointing. However, the bilateral nerve-sparing method achieved much
      better results inasmuch as about 50% of the patients reported recovery of
      erections sufficient for sexual intercourse.

PMID- 11315584
TI  - [Minimally invasive bone anchor in therapy of female stress incontinence. A good
      concept?].
AB  - Transvaginal pubic bone anchoring represents a minimally invasive technique for
      cystourethropexy or urethral sling suspension. This study assesses the results of
      this procedure. Cystourethropexy was performed in 4 and a sling procedure in 13
      of 17 patients. The stress incontinence showed a median improvement from grade 2
      to 1.35 (p = 0.01). Nine patients had impaired vaginal wound healing with urge
      symptoms. Revision was necessary in eight of them. An unfavorable outcome could
      not be significantly correlated with the surgical technique, the surgeon, the
      patient's age or the number of previous operations. The technique of minimally
      invasive bone anchoring must be regarded as unsuitable in view of the largely
      poor wound healing associated with irritation symptoms.

PMID- 11315585
TI  - [Bilateral kidney tumor. Therapy management and histopathological results with
      long-term follow-up of 66 patients].
AB  - Bilateral renal cell carcinoma is detected at an incidence rate of 1.6-6% of all
      renal tumors. The management, histopathological results and the long-term follow
      up of 66 patients with bilateral renal cell carcinoma (29 synchronous, 37
      asynchronous tumors) are presented in this issue. The incidence rate of bilateral
      renal cell carcinoma (RCC) at our hospital was 3.5%. Nephron-sparing surgery
      should be used first for the smaller and favourably located tumor when radical
      nephrectomy of the contralateral tumor is necessary. Thus, the patients can be
      spared dialysis. The histopathological results showed a significantly higher
      incidence rate of chromophil RCCs in cases of synchronous bilateral renal tumors
      (36%). The 5-year survival rate was 82%. Patients with asynchronous renal cell
      carcinomas were significantly younger than those with synchronous RCCs (median
      age: 60.2 years). The histopathological results were similar to unilateral renal
      cell carcinomas. Clear cell carcinoma was detected in 70% of cases. The 5-year
      survival rate was 61% and lower than that of synchronous tumors (82%). There was
      no significant difference because of the small number of cases. Current
      standardised techniques of nephron-sparing surgery achieve good survival rates,
      therefore making bilateral nephrectomy only necessary in very poor cases. In
      cases of chromophil renal cell carcinomas, the contralateral kidney should always
      be carefully examined, because these tumors were significantly more often
      detected to be bilateral. The risk of also developing a tumor in the
      contralateral kidney increases with decreasing age at first manifestation (< 55
      years, 6%). Especially in those younger than 55 years, partial nephrectomy seems
      to be recommended for unilateral renal tumors in patients with a normal
      contralateral kidney (tumor size < 4 cm in diameter).

PMID- 11315586
TI  - [Hyaluronic acid and hyaluronidase. 2 new bladder carcinoma markers].
AB  - The heterogeneity of bladder cancer concerning progress of recurrence is an
      essential characteristic of this disease. Hyaluronic acid (HA) and its degrading
      enzyme hyaluronidase (HAase) are intricately associated with bladder cancer
      angiogenesis and metastasis. Tumor-associated HA and HAase are secreted in urine.
      In 513 urine specimens (261 bladder cancer patients, 252 patients without bladder
      cancer) and 83 bladder tissue specimens (71 bladder tumors, 12 normal bladder
      tissues), the accuracy of HA and HAase as tumor markers was studied. Elevated
      urinary HA levels (> or = 500 ng/ml), indicating a positive HA test, suggest the
      presence of bladder cancer regardless of tumor grade. Elevated urinary HAase
      levels (> or = 10 mU/mg) indicate high-grade (G2/G3) bladder cancer. The combined
      HA-HAase urine test showed 91% sensitivity and 84% specificity to detect bladder
      cancer. The HA-HAase test is equally sensitive for monitoring tumor recurrence.
      Immunohistochemistry (IHC) staining of HA and HAase in the G1 and G2/G3 bladder
      cancer specimens was significantly (p < 0.001) higher than in normal bladder
      tissue. HA and HAase appear to be useful markers in the diagnosis of bladder
      cancer. When compared with other noninvasive tests, the HA-HAase urine test may
      be less expensive and more accurate.

PMID- 11315587
TI  - [Side-fire laser coagulation of the prostate with the neodymium:YAG-laser. Long
      term outcome].
AB  - Transurethral laser prostatectomy has been widely used in patients with benign
      prostatic obstruction (BPO) with good short-term results and an excellent safety
      profile. We investigated how stable the results of side-firing visual laser
      coagulation of the prostate are during long-term follow-up to evaluate whether
      laser prostatectomy can really be an alternative to transurethral resection of
      the prostate (TURP). Between January 1993 and December 1995 a total of 59
      patients underwent visual transurethral side-firing laser coagulation of the
      prostate (Urolase, Bard Inc., Murray Hill, NJ, USA). The patients were monitored
      at 1, 3, 6, and 12 months and then reevaluated after a mean of 33 months. As
      expected, at the 1-year follow-up there was a significant improvement in peak
      flow rate, post-void residual urine, international prostate symptom score (IPSS)
      and quality of life index (QoL). After a mean of 33 months, 15% of the patients
      required reoperation due to persistent BPO. In the remaining patients, peak flow
      rate and post-void residual urine were stable. However, the QoL index increased
      during long-term follow-up and no longer differed from the preoperative value
      after 33 months. The side-firing laser coagulation of the prostate does not seem
      to be a sufficient therapeutic alternative to TURP in the treatment of BPO.

PMID- 11315588
TI  - [Postobstructive polyuria in unilateral hydronephrosis. A case with 58 l/day].
AB  - Increased urinary outputs are common after release of bilateral ureteral or
      subvesical obstruction. However, polyuria is rare following unilateral
      obstruction. We report a case of excessive postobstructive diuresis of more than
      58,000 ml per day (204 l in 10 days) after release of a left ureteral obstruction
      in a 56-year-old female, being the highest amounts reported in the literature.
      Polyuria was derived from the obstructed as well as from the normal contralateral
      kidney. The involved pathomechanism is complex and not completely understood.
      Treatment includes careful monitoring of the patient and replacement of fluid and
      electrolytes. In our case complete recovery of kidney function was observed after
      several days.

PMID- 11315589
TI  - [Interdisciplinary consensus in diagnosis and therapy of testicular tumors.
      Results of an update conference founded on evidence-based medicine (EBM)].

PMID- 11315590
TI  - [Adrenal gland tumor--diagnosis and therapy].

PMID- 11315591
TI  - The plasticity of the brain.

PMID- 11315592
TI  - The clinical benefit of imaging striatal dopamine transporters with [123I]FP-CIT
      SPET in differentiating patients with presynaptic parkinsonism from those with
      other forms of parkinsonism.
AB  - [123I]FP-CIT (N-omega-fluoropropyl-2 beta-carbomethoxy-3 beta-(4
      iodophenyl)nortropane) has been developed successfully as a radioligand for
      single-photon emission tomography (SPET) imaging of dopamine transporters, which
      are situated in the membrane of dopaminergic neurons. Imaging of these
      transporters has shown promise as a clinical tool to detect degeneration of the
      dopaminergic nigrostriatal pathway. Several "presynaptic parkinsonian" syndromes,
      such as Parkinson's disease or multiple system atrophy, are characterised by
      degeneration of the nigrostriatal pathway. [123I]FP-CIT SPET imaging studies have
      shown the ability to detect loss of striatal dopamine transporters in such
      syndromes. However, in clinical practice it is sometimes difficult, but
      important, to discriminate patients with "presynaptic parkinsonism" from those
      with other forms of parkinsonism not characterised by loss of presynaptic
      dopaminergic cells (e.g. psychogenic parkinsonism or drug-induced postsynaptic
      parkinsonism). In these inconclusive cases, it may be of value to confirm or
      exclude the existence of degeneration of nigrostriatal dopaminergic cells by
      using imaging techniques such as [123I]FP-CIT SPET. Using [123I]FP-CIT SPET, we
      have imaged the striatal dopamine transporters in a group of patients with
      inconclusive forms of parkinsonism, and, moreover, have been able to perform
      clinical follow-up of these patients 2-4 years after imaging. In 33 inconclusive
      cases, ratios of specific to non-specific binding were calculated for the caudate
      nucleus and putamen following [123I]FP-CIT SPET imaging and compared with ratios
      obtained in healthy controls. In nine of the patients, degeneration of the
      nigrostriatal pathway was found scintigraphically and in all these cases,
      presynaptic parkinsonism was confirmed by clinical follow-up. In the other 24
      subjects no degeneration was found scintigraphically. Forms of parkinsonism other
      than the presynaptic were confirmed at follow-up in 19 cases, and in three cases
      no conclusive diagnosis was established, but presynaptic parkinsonism was
      excluded clinically. A clinical diagnosis of presynaptic parkinsonism was
      established in two cases: one case of multiple system atrophy (in this patient
      loss of dopamine D2 receptors was found with [123I]iodobenzamide SPET performed 2
      weeks after [123I]FP-CIT imaging) and one case of Parkinson's disease. Our data
      suggest that the positive predictive value of [123I]FP-CIT imaging is very high,
      and although the negative predictive value is lower, dopamine transporter imaging
      offers the prospect of a quick, objective method to confirm or exclude
      presynaptic parkinsonism in inconclusive cases.

PMID- 11315593
TI  - High uptake of L-3-[123I]iodo-alpha-methyl tyrosine in pilocytic astrocytomas.
AB  - Despite a favourable prognosis, pilocytic astrocytomas may exhibit signs of
      malignancy on various neuroimaging modalities. This retrospective analysis was
      conducted to determine whether scintigraphic features of malignancy are also
      found on single-photon emission tomography (SPET) using L-3-[123I]iodo-alpha
      methyl tyrosine (IMT) as a tracer. Twenty patients with pilocytic astrocytomas
      were retrospectively selected from a large series of patients referred for the
      evaluation of primary or recurrent brain tumours. IMT SPET was performed in 16
      patients, positron emission tomography (PET) using 2-[18F]fluoro-2-deoxy-D
      glucose (FDG) was available in 10 of the patients and SPET using technetium-99m
      tetrofosmin or thallium-201 had been performed in 11. Image analysis was
      performed using standard protocols to determine how many patients exceeded the
      respective thresholds of malignancy. Features of malignancy were found in 7/16
      IMT SPET studies, in 7/10 FDG PET studies and in 7/11 of the residual SPET
      investigations. A significant correlation of tumour size and IMT uptake in
      primary pilocytic astrocytomas indicated partial volume effects to partly account
      for the differential uptake behaviour (n = 10, r = 0.87, P < 0.05). Differences
      in IMT uptake in primaries (1.7 +/- 0.6, n = 10) and in recurrent tumours (2.3 +/
      0.7, n = 6) did not attain statistical significance. IMT SPET results indicative
      of malignancy are regularly found in pilocytic astrocytomas, despite their good
      prognosis. No uptake may be detected in largely cystic or in small tumours.

PMID- 11315594
TI  - Diagnosis of recurrent head and neck squamous cell carcinoma with 3-[123I]iodo-L
      alpha-methyltyrosine SPET.
AB  - The distribution of 3-[123I]iodo-L-alpha-methyltyrosine (123I-3-IMT) in the
      tumour region of 21 patients with clinically suspected recurrent squamous cell
      head and neck carcinoma was studied. Single-photon emission tomography (SPET)
      imaging of the head and neck region was performed 10 min after the injection of
      130-170 MBq 123I-3-IMT using a dual-detector gamma camera. Images were
      interpreted visually and classified as positive or negative for recurrent
      disease. In addition, target to background ratios (T/B) were measured using semi
      automated region of interest analysis. IMT-SPET results were compared with the
      data derived from clinicopathological follow-up. IMT-SPET detected recurrent
      disease in 14 of 15 patients (sensitivity 93%). T/B ratios ranged between 1.5 and
      2.4 (mean 1.88). One patient with a small tumour (1.2 cm) had a false-negative
      result. This is attributed to the limited spatial resolution of the SPET system.
      Five of six patients were correctly diagnosed to be negative for tumour
      recurrence. T/B ratios ranged between 1.2 and 1.4 (mean 1.30). In one patient IMT
      SPET was positive without evidence of recurrence based on clinicopathological
      follow up. This finding was probably due to uptake into inflammatory tissue. IMT
      SPET appears to be a sensitive tool (93%) for the detection of recurrent head and
      neck squamous cell carcinoma. Further studies with 123I-3-IMT as a metabolic
      tracer for the detection of head and neck cancer recurrence using SPET are
      recommended.

PMID- 11315595
TI  - Extended combined 99mTc-white blood cell and bone imaging improves the diagnostic
      accuracy in the detection of hip replacement infections.
AB  - Although the diagnosis of hip prosthesis infection is clinically important, X-ray
      studies, blood chemistry and synovial fluid aspiration may be unreliable for this
      purpose. The aim of this study was to evaluate whether extending the time for
      technetium-99m labelled leucocyte imaging to 24 h post injection improves the
      accuracy of diagnosis of hip replacement infections. We studied 64 symptomatic
      patients with hip prostheses. The presence of infections was verified by
      intraoperative bacterial cultures, and infection was excluded either by negative
      operative findings or by follow-up for at least 1 year. Leucocyte imaging was
      done with 99mTc-hexamethylpropylene amine oxime (HMPAO)-labelled leucocytes at 2
      4 h (routine images) and at 24 h (late images) after the injection of the
      leucocytes. In addition, bone imaging was carried out with 99mTc
      hydroxydiphosphonate (HDP) at the arterial, soft tissue and metabolic phases. A
      standardised method was used to compare leucocyte images with bone metabolic
      images. In this material, there were six confirmed infections. All the bone
      imaging methods had a sensitivity of 100% in detecting prosthesis infections
      whereas the specificity varied from only 2% to 82%. Routine leucocyte imaging was
      less sensitive (50% vs 83%) and less specific (90% vs 100%) than late leucocyte
      imaging. All tests had a high negative predictive value for excluding infection
      (95%-100%). However, both bone (10%-38%) and routine leucocyte imaging (33%)
      showed a poor positive predictive value (PPV), whereas late leucocyte imaging had
      a PPV of 100% and a diagnostic accuracy of 98%. We conclude that late leucocyte
      imaging improves the specificity of diagnosis of infected hip prostheses. This
      type of imaging procedure should be combined with three-phase bone scintigraphy
      in studies of patients with painful joint replacement.

PMID- 11315596
TI  - Assessment of leg oedema by dynamic lymphoscintigraphy with intradermal injection
      of technetium-99m human serum albumin and load produced by standing.
AB  - This study was a preliminary evaluation of the utility of dynamic
      lymphoscintigraphy with technetium-99m human serum albumin (HSA) and a load
      produced by standing in the assessment of lymphatic dysfunction in patients with
      leg oedema. The 71 subjects investigated included 53 patients with lymphoedema,
      six with venous occlusion alone and five with lymphovenous occlusion, as well as
      seven normal subjects. After intradermal injection of 99mTc-HSA into an
      interdigital space in each foot, dynamic scintigrams were recorded with the
      patient supine for 15 min. The subjects then stood in place and images were
      recorded for an additional 15 min. Relative changes in lymphatic tracer transport
      before and after standing were analysed on time-activity curves (TACs). This test
      was compared with a conventional test in a supine position in six patients with
      lymphoedema, and was repeated in five other patients with lymphoedema. It was
      found that in the normal limbs, a standing load activated tracer transport to the
      draining lymphatic vessels, resulting in a rapid stepwise increase in tracer
      activity, large spiking waves and a decreasing phase following a peak in tracer
      activity on TACs. In 59 lymphoedematous limbs, including some with a mild form of
      oedema without morphological abnormalities on scintigrams, this load failed to
      induce a sufficient activation of tracer transport, and the frequencies of each
      of the three normally appearing changes described above significantly decreased
      compared with those in the 14 normal limbs (P < 0.0001, P < 0.01 and P < 0.0001,
      respectively). In addition, there were significant reductions in the relative
      increases in maximum activity and clearance times after standing (both P <
      0.0001). These abnormalities significantly correlated with the grade of severity
      of oedema. Six limbs with lymphovenous occlusion showed significant reductions in
      tracer transport compared to six limbs with venous occlusion. Lymphatic
      dysfunction was accentuated more by this test than by the conventional test, and
      repeated tests showed consistent results in the same individuals. It is concluded
      that under a standardized load, this quick test seems of value in providing a
      sensitive and objective assessment of lymphatic dysfunction in the lower limbs,
      and is also advantageous for image interpretation since accelerated tracer
      transport clearly visualizes compromised lymphatics. This test may also be
      helpful in distinguishing purely venous oedema from mixed lymphovenous disease.

PMID- 11315597
TI  - Predictive value of technetium-99m sestamibi in patients with multiple myeloma
      and potential role in the follow-up.
AB  - Technetium-99m 2-methoxyisobutylisonitrile (99mTc-MIBI or setamibi) has recently
      been proposed for use in the evaluation of multiple myeloma (MM). The aims of
      this study were to investigate its potential predictive value in patients with MM
      and its possible role in the follow-up. Thirty patients with MM who had undergone
      two 99mTc-MIBI scintigraphic studies at least 2 months apart constituted the
      study group; 22 of them received chemotherapy in the interval between the two
      scans. The scans were classified as showing pattern N when only physiological
      uptake was present, pattern D when diffuse bone marrow uptake was observed,
      pattern F when areas of focal uptake of the tracer were evident, and pattern F +
      D when both D and F patterns were observed. Comparative 99mTc-MIBI scintigraphy
      was considered indicative of disease progression when there was a worsening of
      the pattern (i.e. from N to D, or from N or D to F or to F + D) or an increase in
      the pattern D semiquantitative score. It was considered indicative of disease
      improvement when the opposite trend was observed; otherwise, it was considered to
      document a stable condition. A significant association was observed between the
      baseline scintigraphic pattern and clinical status at follow-up in the group of
      patients evaluated after chemotherapy (chi 2 = 16.7, P < 0.05). A negative
      baseline 99mTc-MIBI scintigram showed a high predictive accuracy (100%) for
      remission, while the presence of pattern F or F + D was often associated with a
      less favourable outcome. A multivariate analysis showed that 99mTc-MIBI uptake
      pattern has an added value in relation to known prognostic variables such as C
      reactive protein. 99mTc-MIBI scintigraphy patterns at follow-up were
      significantly associated with the clinical status evaluated after chemotherapy
      (chi 2 = 32.6, P < 0.0001). Considering pattern N as indicating remission,
      pattern D stable condition, and pattern F or F + D progressive disease, a high
      concordance between scintigraphic findings and clinical status was found in the
      22 patients undergoing chemotherapy (91%). Variation in 99mTc-MIBI findings
      comparing baseline and follow-up evaluations was significantly associated with
      clinical status both in patients undergoing chemotherapy (chi 2 = 26.5, P <
      0.0005) and in those not undergoing chemotherapy (chi 2 = 8.0, P < 0.005). In
      conclusion, the results of this study suggest a prognostic value of 99mTc-MIBI
      scintigraphy in patients with MM and a potential role during the follow-up.

PMID- 11315598
TI  - Parametric oesophageal multiple swallow scintigraphy for validation of dysphageal
      symptoms during external beam irradiation of mediastinal tumours.
AB  - The aim of the study was to evaluate dysphageal symptoms and to measure the
      effect of local analgesic treatment using parametric oesophageal multiple swallow
      scintigraphy (PES) during external beam irradiation of the mediastinal region.
      Fifteen patients (most with lung cancer) with dysphagia grade II underwent PES
      during external beam radiotherapy of the mediastinum before and after application
      of local analgesics. Dynamic parametric condensed images were recorded. The
      intensity of clinical symptoms was correlated with the emptying rate at 10 s (ER
      10 s) and the mean transit time (MTT). Visual analysis of the images was
      performed and the results were correlated with the fields of irradiation portals.
      Of the 15 patients, 12 showed a correlation between irradiation portals and the
      region of oesophageal motility disorder. Concordant results of clinical symptoms
      and PES data were found. In nine patients with a decrease in dysphagia following
      local analgesia, an increase in mean ER-10 s and a decrease in MTT were observed.
      In three patients with deterioration in clinical symptoms after analgesic
      treatment, a similar decrease in mean ER-10 s was found, though MTT remained
      constant. In three patients with normal values, motility disorders were detected
      in the dynamic study. In conclusion, PES was found to be a sensitive tool for the
      validation of dysphageal symptoms in patients during external beam irradiation of
      mediastinal tumours and for the evaluation and quantification of the efficacy of
      local analgesic treatment. Additional visual analysis of the dynamic study is
      helpful in diagnosing minimal disorders.

PMID- 11315599
TI  - Comparison between terminal slope rate constant and "slope/intercept" as measures
      of glomerular filtration rate using the single-compartment simplification.
AB  - Several whole-body variables are available for indexing glomerular filtration
      rate (GFR), including extracellular fluid volume (ECF volume, ECV), which has the
      advantage that GFR based only on the terminal exponential, alpha 2, of the
      chromium-51 ethylene diamine tetraacetic acid (51Cr-EDTA) plasma clearance curve
      is a measure already indexed for ECV. This slope-only method, however, is open to
      the theoretical criticism of a lack of robustness not present in the more
      conventional slope/intercept method, which generates GFR in absolute units before
      indexation to body surface area (BSA). To further evaluate the slope-only method,
      a large database of routine three-sample GFR measurements, based on 51Cr-EDTA,
      was analysed with the aim of comparing GFR/BSA with GFR/ECV, identifying the main
      sources of error in their respective measurements and explaining why they might
      be discrepant. The database was subdivided into 304 patients (group A) in whom
      the correlation coefficient of the fit to the three data points was greater than
      0.99 and 31 patients in whom it was less than 0.99 (noisy data; group B). There
      was modest agreement between GFR/BSA and GFR/ECV in group A (r = 0.77; mean ratio
      1.01 +/- 0.21). The difference between them correlated significantly with BSA (r
      = 0.52; P < 0.001), as would be expected given that small individuals have a
      relatively high BSA. Subdividing group A into four subgroups stratified according
      to BSA led to a slight improvement in the correlation between GFR/BSA and
      GFR/ECV. Because an error in alpha 2 is balanced by an opposing error in the
      intercept (which leads to a change in distribution volume in the opposite
      direction), and therefore impacts on both GFR/BSA and GFR/ECV, whereas an error
      in administered dose affects only GFR/BSA, it is possible to evaluate such errors
      by examining the respective relationships of GFR/BSA and GFR/ECV with indexed
      ECV. In group A, GFR/BSA correlated positively with ECV/1.73 m2, not surprisingly
      as ECV/BSA is effectively the ratio GFR/BSA to GFR/ECV, while GFR/ECV correlated
      negatively with ECV/1.73 m2. This implies that errors other than alpha 2,
      probably principally in administered dose, were as important as errors in alpha
      2. This conclusion was supported by disappearance of the positive correlation
      between GFR/BSA and ECV/BSA in group B, brought about by the greater errors in
      alpha 2 in this group. This study suggests that, because of the effects of errors
      in the slope/intercept method that do not affect alpha 2, GFR based on slope only
      is at least as robust as that based on slope/intercept.

PMID- 11315600
TI  - Accuracy of technetium-99m tetrofosmin myocardial perfusion imaging in the
      detection of spontaneous recanalization in patients with acute anterior
      myocardial infarction.
AB  - To avoid the haemorrhagic risk of unnecessary thrombolysis in acute myocardial
      infarction (MI), early and precise diagnosis of spontaneous recanalization (SR)
      of the infarct-related artery is required. To clarify the accuracy of technetium
      99m tetrofosmin myocardial single-photon emission tomography (SPET) in the
      detection of SR in patients with acute anterior MI, electrocardiography (ECG),
      echocardiography and 99mTc-tetrofosmin SPET imaging were performed in 49 patients
      with acute anterior MI before emergency coronary angiography. Defect score was
      calculated as the sum of the perfusion defects of each segment: from 3 (complete
      defect) to 0 (normal perfusion). Echocardiographic asynergic score (the sum of
      asynergic grades) and the greatest ST elevation of the 12-lead ECG on admission
      were also measured. SR was defined as Thrombolysis in Myocardial Infarction
      (TIMI) grade 3 flow on emergency coronary angiography. Defect score in 11
      patients with SR (9.2 +/- 3.7) was significantly lower than that in 38 patients
      without SR (18.5 +/- 5.0) (P < 0.001), whereas there were no significant
      differences in asynergic score and ST elevation between the two groups. From the
      receiver operating characteristic curves, the optimal cut-off points of defect
      score, asynergic score and ST elevation for the detection of SR were calculated
      to be 12, 13 and 3.5, respectively. The sensitivity and specificity of the
      scintigraphic defect score (91% and 89%) were significantly higher than those of
      the asynergic score (64% and 68%) and ST elevation (73% and 71%). Thus, 99mTc
      tetrofosmin SPET imaging on admission is a very accurate method for the detection
      of SR in patients with acute anterior MI.

PMID- 11315601
TI  - Use of [11C]acetate and [15O]O2 PET for the assessment of myocardial oxygen
      utilization in patients with chronic myocardial infarction.
AB  - Carbon-11 acetate positron emission tomography (PET) has been widely used to
      assess regional oxidative metabolism of the heart. However, the accuracy of
      [11C]acetate PET in assessing oxidative metabolism in infarcted myocardium
      remains controversial. Thirteen patients with stable coronary artery disease and
      old myocardial infarction were studied. The 15O-based PET studies yielded
      regional blood flow (rMBF, ml/min/g) and oxygen consumption (rMMRO2, ml/min/g),
      which was compared with the myocardial clearance rate constant (kmono) of
      [11C]acetate in segments with rMBF > or = 75% (group A), 50%-74% (group B) or <
      50% (group C) of the normal reference segment. Mean MBF was 0.96 +/- 0.08
      ml/g/min in group A, 0.67 +/- 0.06 ml/g/min in group B and 0.42 +/- 0.07 ml/g/min
      in group C segments. The segmental rMMRO2 correlated linearly with kmono (r =
      0.89, P < 0.001, y = 0.61x + 0.026). The kmono/rMMRO2 ratio was comparable in the
      group A and B segments (0.99 +/- 0.19 vs 1.07 +/- 0.21, P = NS). However, the
      ratio was significantly higher in the group C segments (1.28 +/- 0.35, P =
      0.037). It is concluded that kmono of [11C]acetate correlates linearly with
      rMMRO2 determined by [15O]O2 inhalation. However, kmono appears to yield higher
      rMMRO2 estimates than the [15O]O2 method in low-flow areas.

PMID- 11315602
TI  - Validation of myocardial blood flow estimation with nitrogen-13 ammonia PET by
      the argon inert gas technique in humans.
AB  - We simultaneously determined global myocardial blood flow (MBF) by the argon
      inert gas technique and by nitrogen-13 ammonia positron emission tomography (PET)
      to validate PET-derived MBF values in humans. A total of 19 patients were
      investigated at rest (n = 19) and during adenosine-induced hyperaemia (n = 16).
      Regional coronary artery stenoses were ruled out by angiography. The argon inert
      gas method uses the difference of arterial and coronary sinus argon
      concentrations during inhalation of a mixture of 75% argon and 25% oxygen to
      estimate global MBF. It can be considered as valid as the microspheres technique,
      which, however, cannot be applied in humans. Dynamic PET was performed after
      injection of 0.8 +/- 0.2 GBq 13N-ammonia and MBF was calculated applying a two
      tissue compartment model. MBF values derived from the argon method at rest and
      during the hyperaemic state were 1.03 +/- 0.24 ml min-1 g-1 and 2.64 +/- 1.02 ml
      min-1 g-1, respectively. MBF values derived from ammonia PET at rest and during
      hyperaemia were 0.95 +/- 0.23 ml min-1 g-1 and 2.44 +/- 0.81 ml min-1 g-1,
      respectively. The correlation between the two methods was close (y = 0.92x +
      0.14, r = 0.96; P < 0.0001). No indication was found for limited extraction of
      ammonia in the myocardium. The high concordance of global MBF values derived with
      argon and ammonia indicates that the implicit correction of spillover and
      recovery effects, incorporated in the model by including an effective blood
      volume parameter, works correctly quantitatively. Our data provide the previously
      missing human validation of MBF measurements from 13N-ammonia PET.

PMID- 11315603
TI  - Use of technetium-99m HMPAO scintigraphy for the detection of amiodarone lung
      toxicity in a rabbit model.
AB  - Amiodarone (AD) is a very effective anti-arrhythmic drug, but its use is often
      associated with serious pulmonary complications such as pneumonitis and
      interstitial pulmonary disease. The aim of this study was to investigate the
      relationship between the amount of amiodarone intake (and the related development
      of lung toxicity) and the lung uptake of technetium-99m labelled D,L
      hexamethylpropylene amine oxime (HMPAO). Eighteen white female New Zealand
      rabbits were divided into three groups and fed AD by gavage at doses of 10 (group
      A), 50 (group B) or 150 (group C) mg/kg daily. 99mTc-HMPAO scintigraphy was
      performed at baseline and after 1, 2, 3 and 4 weeks of drug intake. Anterior
      images of 1 min duration were acquired at 30 min after the injection of 37 MBq
      99mTc-HMPAO. Regions of interest (ROIs) were drawn on the lungs (L) and the upper
      limb (B) as the background. L/B ratios were calculated using the mean counts. In
      groups A and B histopathological evaluation of the lungs of all rabbits was
      performed at the end of the 4 weeks of AD intake, while in group C it was
      performed at 2 weeks because of increased mortality. At baseline, mean L/B ratios
      for groups A, B and C were 2.8 +/- 0.3, 2.8 +/- 0.3 and 2.8 +/- 0.4,
      respectively. After 3 weeks of AD intake, L/B ratios increased to 4.1 +/- 0.6 and
      4.8 +/- 0.6 in groups A and B, respectively. The L/B ratio was 3.6 +/- 0.2 after
      1 week of AD intake in group C. The correlation coefficients between the lung
      uptake of 99mTc-HMPAO and AD doses for groups A, B and C were r = 0.51 (P =
      0.037), r = 0.74 (P = 0.0002) and r = 0.96 (P = 0.0001), respectively.
      Histopathological findings related to AD lung toxicity, such as interstitial
      pneumonitis and foamy alveolar macrophages, were observed more frequently in
      groups B and C than in group A. According to our findings, 99mTc-HMPAO lung
      uptake is correlated with AD dose. 99mTc-HMPAO lung imaging can demonstrate AD
      induced lung injury.

PMID- 11315604
TI  - Fluorine-18 2-deoxy-2-fluoro-D-glucose PET in the preoperative staging of breast
      cancer: comparison with the standard staging procedures.
AB  - The present study compared the diagnostic accuracy of fluorine-18 2-deoxy-2
      fluoro-D-glucose positron emission tomography (FDG-PET) with conventional staging
      techniques. The differentiation between malignant and benign lesions and the
      detection of multifocal disease, axillary and internal lymph node involvement,
      and distant metastases were evaluated. One hundred and seventeen female patients
      were prospectively examined using FDG-PET and conventional staging methods such
      as chest X-ray, ultrasonography of the breast and liver, mammography and bone
      scintigraphy. All patients were examined on a modern full-ring PET scanner.
      Histopathological analysis of resected specimens was employed as the reference
      method. The readers of FDG-PET were blinded to the results of the other imaging
      methods and to the site of the breast tumour. The sensitivity and specificity of
      FDG-PET in detecting malignant breast lesions were 93% and 75% respectively. FDG
      PET was twofold more sensitive (sensitivity 63%, specificity 95%) in detecting
      multifocal lesions than the combination of mammography and ultrasonography
      (sensitivity 32%, specificity 93%). Sensitivity and specificity of FDG-PET in
      detecting axillary lymph node metastases were 79% and 92% (41% and 96% for
      clinical evaluation). FDG-PET correctly indicated distant metastases in seven
      patients. False-positive or false-negative findings were not encountered with FDG
      PET. Chest X-ray was false-negative in three of five patients with lung
      metastases. Bone scintigraphy was false-positive in four patients. Three patients
      were upstaged since FDG-PET detected distant metastases missed with the standard
      staging procedure. It is concluded that, compared with the imaging methods
      currently employed for initial staging, FDG-PET is as accurate in interpreting
      the primary tumour and more accurate in screening for lymph node metastases and
      distant metastases. Due to a false-negative rate of 20% in detecting axillary
      lymph node metastases, FDG-PET cannot replace histological evaluation of axillary
      status.

PMID- 11315605
TI  - A comparison of targeting of neuroblastoma with mIBG and anti L1-CAM antibody mAb
      chCE7: therapeutic efficacy in a neuroblastoma xenograft model and imaging of
      neuroblastoma patients.
AB  - Iodine-131 labelled anti L1-CAM antibody mAb chCE7 was compared with the
      effective neuroblastoma-seeking agent 131I-labelled metaiodobenzylguanidine
      (MIBG) with regard to (a) its therapeutic efficacy in treating nude mice with
      neuroblastoma xenografts and (b) its tumour targeting ability in neuroblastoma
      patients. The SK-N-SH tumour cells used in the mouse experiments show good MIBG
      uptake and provide a relatively low number of 6,300 binding sites/cell for mAb
      chCE7. Tumours were treated with single injections of 131I-MIBG (110 MBq) and
      with 131I-labelled mAb chCE7 (17 MBq) and both agents showed antitumour activity.
      After therapy with 131I-chCE7, the subcutaneous tumours nearly disappeared;
      treatment with 131I-MIBG was somewhat less effective, resulting in a 70%
      reduction in tumour volume. A calculated tumour regrowth delay of 9 days occurred
      with a radioactivity dose of 17 MBq of an irrelevant control antibody mAb 35,
      which does not bind to SK-N-SH cells, compared with a regrowth delay of 34 days
      with 131I-mAb chCE7 and of 24 days with 131I-MIBG. General toxicity appeared to
      be mild, as assessed by a transient, approximate 10% maximum decrease in body
      weight during the treatments. The superior growth inhibition achieved by 131I
      chCE7 compared with 131I-MIBG can be explained by its prolonged retention in the
      tumours, due to slower normal tissue and plasma clearance. Cross-reaction of mAb
      chCE7 with L1-CAM present in normal human tissues was investigated by direct
      binding of radioiodinated mAb to frozen tissue sections. Results showed a strong
      reaction with normal human brain tissue and weak but detectable binding to normal
      adult kidney sections. Seven patients with recurrent neuroblastoma were
      sequentially imaged with 131I-MIBG and 131I-chCE7. The results underlined the
      heterogeneity of neuroblastoma and showed the two imaging modalities to be
      complementary. 131I-chCE7 scintigraphy may have clinical utility in detecting
      metastases which do not accumulate 131I-MIBG, and the antibody may hold potential
      for radioimmunotherapy, either by itself or in combination with 131I-MIBG.

PMID- 11315606
TI  - Uptake of gallium-67 citrate in clean surgical incisions after colorectal
      surgery.
AB  - Non-specific accumulation of gallium-67 citrate (gallium) in uncomplicated
      surgical incisions is not uncommon. It is important to know the normal pattern of
      gallium uptake at surgical incision sites in order to properly interpret the
      gallium scan when investigating possible wound infection in patients who have
      undergone abdominal surgery. We studied 42 patients without wound infection after
      colorectal surgery and performed gallium scans within 40 days after surgery.
      Patients were divided into three groups according to the interval between the
      operation and the scan. In group A (26 patients) gallium scan was performed
      within 7 days after surgery, in group B (8 patients) between 8 and 14 days after
      surgery, and in group C (8 patients) between 15 and 40 days after surgery. Our
      data showed that in group A, 61.5% had gallium accumulation at the surgical
      incision site. In group B, 50% had accumulation of gallium at the surgical
      incision site, while in group C only one patient (12.5%) showed gallium uptake.
      It is concluded that the incidence of increased gallium uptake at clean surgical
      incision sites is high after colorectal surgery. Nuclear medicine physicians
      should bear in mind the high incidence of non-specific gallium uptake at such
      sites during the interpretation of possible wound infection in patients after
      colorectal surgery.

PMID- 11315607
TI  - Reduced myocardial carbon-11 hydroxyephedrine retention is associated with poor
      prognosis in chronic heart failure.
AB  - Abnormalities of the autonomic nervous system are known to be of prognostic
      significance in chronic heart failure (CHF). The prognostic value of positron
      emission tomography (PET) imaging of cardiac autonomic innervation in CHF has not
      been explored previously. We retrospectively studied the survival data of 46 NYHA
      class II-III CHF patients (mean LVEF 35% +/- 8%) who had undergone carbon-11
      hydroxyephedrine (11C-HED) studies at the Turku PET Centre between August 1992
      and March 1996. The origin of CHF was dilated cardiomyopathy in 13 of the 46
      patients and coronary artery disease with at least one prior myocardial
      infarction in the remaining 33. Data on causes of death and heart transplantation
      were collected, and the statistically significant predictors of prognosis were
      analysed using Cox's proportional hazards regression. During the mean follow-up
      period of 55 +/- 19 months, 11 deaths occurred and two patients underwent heart
      transplantation successfully. Eleven end-points were classified as cardiac (nine
      sudden cardiac deaths and two deaths due to progressive heart failure) and two as
      non-cardiac. When divided into two groups based on the median of 11C-HED
      retention (mean 0.184 +/- 0.061, median 0.183), eight end-points (death or
      cardiac transplantation) were reached in the group with 11C-HED retention below
      the median and three in the group with 11C-HED retention above the median (P <
      0.02). In proportional hazards regression analysis, only peak oxygen uptake (peak
      VO2), left ventricular end-diastolic volume and HED retention were found to be
      statistically significant. It is concluded that 11C-HED PET provides independent
      prognostic information in patients with CHF.

PMID- 11315608
TI  - Highlights of the European Association of Nuclear Medicine Congress, Paris 2000.
AB  - The recent European Association of Nuclear Medicine Congress, "Paris 2000", was
      an exceptional success, as illustrated by the record attendance. This review
      discusses some of the key new findings presented at the Congress in the fields of
      neurology, cancer therapy, cancer diagnosis, cardiology and miscellaneous other
      areas. The progress being made indicates that nuclear medicine has a bright
      future in the new millennium.

PMID- 11315609
TI  - Seeking a radiobiological explanation for thyroid stunning.

PMID- 11315610
TI  - The history of 123-iodo-methyl tyrosine.

PMID- 11315611
TI  - Literature search strategy for gamma camera emission tomography using coincidence
      imaging.

PMID- 11315612
TI  - Guidelines for indirect radionuclide cystography.

PMID- 11315613
TI  - Guidelines for standard and diuretic renography in children.

PMID- 11315614
TI  - Guidelines for glomerular filtration rate determination in children.

PMID- 11315615
TI  - Guidelines for 99mTc-DMSA scintigraphy in children.

PMID- 11315616
TI  - Guidelines for bone scintigraphy in children.

PMID- 11315617
TI  - Ductal intraepithelial neoplasia of the breast.

PMID- 11315618
TI  - Tumours may be innervated.
AB  - It is generally assumed that tumours are not innervated. However, following an
      accidental observation of a nerve fibre within an adenoma of the ciliary body
      epithelium of the eye, we have further examined two such tumours. One pigmented
      and one non-pigmented adenoma of the ciliary body epithelium (APCE and ANCE,
      respectively) that had been surgically removed from two human eyes were processed
      for ultrastructural evaluation and systematically screened and analysed for the
      occurrence of nerve tissue under a transmission electron microscope. The adenomas
      were composed of epithelial tumour cell strands and interposed vascularised
      connective tissue. Both tumours contained a small number of fine unmyelinated
      nerve fibres containing clear and dense core vesicles. In both adenomas, the
      nerve fibres were located in the tumour periphery close to blood vessels and
      tumour cells. In the APCE, they were also seen in more central areas. Since
      nerves always have a function, this finding, if confirmed in other neoplasms, may
      influence our understanding of such innervated tumours.

PMID- 11315619
TI  - B-cell monoclonality in Helicobacter pylori-associated chronic atrophic
      gastritis.
AB  - B-cell monoclonality has been reported not only in gastric lymphoma, but also in
      1.3-21% of Helicobacter pylori-associated chronic gastritis (Hp-CG) cases. The
      aim of this study was to determine the significance of B-cell monoclonality in Hp
      CG. We examined 134 gastric biopsy specimens from 99 patients with Hp-CG. The
      density of Hp, polymorphonuclear neutrophil activity, chronic inflammation,
      glandular atrophy, and intestinal metaplasia (IM) were scored according to the
      updated Sydney System. B-cell monoclonality was analyzed for immunoglobulin heavy
      chain gene rearrangement using polymerase chain reaction amplification. B-cell
      monoclonality was detected in 6% of informative samples. B-cell monoclonality was
      found in 18% of the samples from Hp-CG patients with marked glandular atrophy but
      in none of the samples from Hp-CG patients with none to moderate glandular
      atrophy. Monoclonality was also detected in 20% of the samples from Hp-CG
      patients with marked IM, in 11% of the samples from Hp-CG patients with moderate
      IM, and in none of the samples from Hp-CG patients without IM. Therefore, B-cell
      monoclonality was significantly more frequent in Hp-CG patients with marked
      glandular atrophy than in Hp-CG patients with none to moderate atrophy. It was
      also more significantly frequent in Hp-CG patients with moderate or marked IM
      than in Hp-CG patients without IM (P < 0.05). Of 35 Hp-CG patients, 26 (74%) had
      identical B-cell populations in the antrum and the corpus, and all were
      polyclonal. The remaining nine (26%) Hp-CG patients had B-cell populations that
      differed in the antrum and the corpus. Four of the nine (44%) showed monoclonal B
      cell populations in at least one gastric biopsy specimen. There were no patients
      with monoclonal B-cell populations in both the antrum and the corpus. These data
      suggest that glandular atrophy and IM in gastric biopsy specimens may be markers
      for gastric mucosa-associated lymphoid tissue (MALT) lymphoma-genesis and that
      multiple gastric biopsy specimens from both the antrum and the corpus may be
      needed to assess the risk of gastric MALT lymphoma.

PMID- 11315620
TI  - Histopathologic changes of thymoma preoperatively treated with corticosteroids.
AB  - Preoperative treatment of thymoma in advanced stages with corticosteroids may
      reduce the size of the tumor, but no precise histologic evaluation has been
      performed. We examined the histopathologic features of pretreatment biopsy and
      posttreatment surgical specimens of eleven cases of thymoma with such treatment
      to see the changes of the histologic subtypes based on Muller-Hermelink
      classification. All specimens were also assessed immunohistochemically for MIB-1
      labeling and apoptotic cells to verify the effectiveness of this pretreatment.
      Seven tumors clinically diminished in size after the treatment with
      corticosteroids. Fungal infection occurred in three cases postoperatively. The
      histology of mixed thymomas (two cases) was converted to that of medullary
      thymoma. Predominantly cortical thymomas (four cases) and cortical thymomas
      (three cases) changed to show similar histologic features; both became epithelial
      rich thymoma with large polygonal tumor cells having indistinct cell borders. In
      contrast, two well-differentiated thymic carcinomas showed at surgery more
      prominent squamoid appearance with distinct cell borders. The apoptotic indices
      of epithelial cells were increased (P = 0.001), and the MIB-1 indices tended to
      be decreased with corticosteroid treatment. These results suggest that there may
      be a histogenetic relationship between medullary and mixed thymomas and also
      between predominantly cortical and cortical thymomas. Corticosteroids may cause
      degenerative changes in the epithelial cells and lymphocytes and, in thymomas in
      advanced stages, corticosteroid pretreatment may be warranted, although attention
      should be paid to infection after surgery.

PMID- 11315621
TI  - Differential expression of human beta-defensin 2 in keratinized and non
      keratinized oral epithelial lesions; immunohistochemistry and in situ
      hybridization.
AB  - Human beta-defensin(hBD)-2, an antimicrobial peptide, is produced by various
      epithelial cells. Because hBD-2 expression in the oral epithelium has not been
      assessed, we investigated its localization in normal oral epithelium and
      epithelial lesions. hBD-2 expression was studied using immunohistochemistry and
      in situ hybridization on formalin-fixed, paraffin-embedded tissue sections from
      30 cases of squamous cell carcinoma and 6 cases of leukoplakia. Immunostaining
      for hBD-2 was more intense in hyperkeratinized than in ortho- or non-keratinized
      epithelium. In contrast, signals for hBD-2 mRNA were frequently stronger in non
      keratinized epithelium than in hyper- or ortho-keratinized epithelium. The
      results suggest that keratinization in oral epithelium plays an important role in
      the biological function of hBD-2 both at the mRNA level and in the retention of
      the peptide in the epithelium.

PMID- 11315622
TI  - Neuron count reevaluation in the myenteric plexus of chagasic megacolon after
      morphometric neuron analysis.
AB  - This study was made with the objective of reevaluating the colon denervation in
      chronic Chagas' disease. The diameters of neuron perikaryons of the myenteric
      plexus were measured on paraffin sections in a ring from the sigmoid in Chagas'
      disease patients, 17 with and 10 without megacolon and in 10 non-chagasic
      controls. All neurons were counted in ten en-echelon sections. Neuron hypertrophy
      only occurred in the group with megacolon, and the average increase in diameter
      was 69.3%. This could generate an error factor in the neuron count by increasing
      the probability of neurons being seen in a greater number of histological
      sections. The original result of the neuron count gave medians of 1264, 1961, and
      2665 in the groups of chagasic patients with megacolon, without megacolon, and in
      the control, respectively. The denervation was greater than 55% in only seven
      megacolon cases (41.2%). After applying a correction factor, the median in the
      group with megacolon was 746, and the denervation was greater than 55% in 13
      cases (76.5%). This occurrence demonstrates the need to apply a correction factor
      when the neuron count in chagasic megacolon is being evaluated and in the other
      pathologies where neuron hypertrophy may be found.

PMID- 11315623
TI  - Pulmonary carcinogenesis induced by ferric nitrilotriacetate in mice and
      protection from it by Brazilian propolis and artepillin C.
AB  - In experiments using the renal carcinogen ferric nitrilotriacetate (Fe-NTA) in
      male ddY mice, primary pulmonary cancers were also induced in bronchiolar and
      alveolar tissues. 4-Hydroxy-2-nonenal (4-HNE) and 8-hydroxy-2'-deoxyguanosine (8
      OHdG), products of oxidative processes, increased in bronchiolar and alveolar
      cells after administration of Fe-NTA. These substances disappeared after oral
      administration of propolis or artepillin C, as shown histochemically, and
      correlated with an anticancer prophylactic effect of propolis and artepillin C.
      From our investigation, lipid peroxidation seems to play an important role in
      pulmonary carcinogenesis. Malignant progression from adenoma of bronchiolar or
      alveolar origin to malignant tumors has been proposed to involve a stepwise
      transformation. In our study, adenomas developed into adenocarcinomas and large
      cell carcinomas after treatment with Fe-NTA. In contrast, after oral
      administration of propolis or artepillin C, adenomas did not progress to
      carcinomas. Instead of developing into large cell cancers, as induced by Fe-NTA
      in control mice, adenomas showed remarkable proliferation of macrophages and
      local anti-oxidant activity after treatment with either propolis or artepillin C.
      Propolis and artepillin C therefore appear to inhibit lipid peroxidation and the
      development of pulmonary cancers.

PMID- 11315624
TI  - Nasal CD56 positive small round cell tumors. Differential diagnosis of
      hematological, neurogenic, and myogenic neoplasms.
AB  - CD56-positive nasal and nasal-type natural killer (NK)/T-cell lymphoma is now a
      well-defined disease entity. Rare cases of blastic NK-cell lymphoma positive for
      CD56 have been recently reported. However, CD56 expression is also identified in
      several types of non-hematopoietic small round cell tumors in which lymphoma is
      included as a differential consideration. Here, we present nine cases of CD56+
      small round cell tumors of histological origin unrelated to nasal NK/T-cell
      lymphoma. Eight of the nine cases presented as solid tumors of the sinonasal
      region. Clinical, histological, ultrastructural, and immunohistochemical
      examination and gene analysis for T-cell receptor (TcR) and immunoglobulin heavy
      chain (IgH) genes and in situ hybridization (ISH) for Epstein-Barr virus (EBV)
      were performed. Two cases presented with features consistent with blastic NK-cell
      lymphoma or lymphoblastic lymphoma of NK-cell phenotype. These cases showed
      features of lymphoblastic lymphoma, phenotypes of sCD3-, cCD3+, CD45+, CD56+,
      TdT+, and human leukocyte antigen (HLA)-DR+, germline of IgH and TcR genes, and
      EBV negative reactivity. One case had myeloid/NK-precursor acute
      leukemia/lymphoma with a phenotype of CD13+, CD33+, CD34+, CD56+, and MPO-. Three
      cases were neurogenic, including one case of olfactory neuroblastoma and two of
      primitive neuroectodermal tumors (PNET). It was difficult to differentiate CD56+
      PNET from blastic NK-cell lymphoma, especially when only paraffin-embedded
      sections were available. Myogenic markers, such as HHF35, alpha-sarcomeric actin,
      and desmin, were positive in three cases of rhabdomyosarcomas. Our findings
      suggest that as CD56 is used more routinely as a marker in immunohistochemical
      staining, the differential diagnosis of extranodal lymphohematological
      malignancies and small round cell tumors will become more complicated.

PMID- 11315625
TI  - Comparative ultrastructural study of cytotoxic granules in nasal natural killer
      cell lymphoma, intestinal T-cell lymphoma, and anaplastic large cell lymphoma.
AB  - Comparative immunohistochemical and ultrastructural studies were performed on
      five nasal natural killer (NK) cell lymphoma cases, two intestinal T-cell
      lymphoma cases, and eight anaplastic large cell lymphoma (ALCL) cases to clarify
      morphological differences in cytotoxic granules among these cytotoxic lymphomas.
      Nasal NK-cell lymphomas and intestinal T-cell lymphomas had fine azurophilic
      granules and displayed dot-like immunostaining of granzyme B- and T-cell
      intracellular antigen 1 (TIA-1), predominantly in the central area of the
      cytoplasm. Ultrastructurally, these NK-cell lymphomas and intestinal T-cell
      lymphomas had two types of cytotoxic granules, type-I granules (dense core
      granules) and type-II granules (multivesicular bodies), which have been
      demonstrated in normal large granular lymphocytes in peripheral blood. However,
      ALCLs did not have azurophilic granules, and only type-II cytotoxic granules were
      found ultrastructurally, even though they showed similar dot-like immunostained
      patterns of granzyme B and TIA-1, as seen in NK-cell lymphomas and intestinal T
      cell lymphomas. Immunoelectron microscopy revealed that TIA-1 was primarily
      located at the periphery of the cytoplasmic granules in the NK-cell lymphoma and
      ALCL cases. These findings suggest that malignant lymphomas with a cytotoxic
      phenotype can be divided into two types, (azurophilic granule)+, (type-I
      granule)+, (type-II granule)+ lymphomas and (azurophilic granule)-, (type-I
      granule)-, (type-II granule)+ lymphomas.

PMID- 11315626
TI  - Molecular and kinetic features of transitional cell carcinomas of the bladder:
      biological and clinical implications.
AB  - Molecular and kinetic analyses have contributed to our understanding of the
      biology of transitional cell carcinomas (TCC) of the bladder. The concordant
      pattern of X-chromosome inactivation of multiple TCCs appearing at different
      times and at different sites and concordant genetic abnormalities in a subset of
      muscle-invasive TCC strongly support a monoclonal origin and a homogeneous tumor
      cell selection throughout the neoplasm. However, topographic intratumor
      heterogeneity results from the accumulation of genetic lesions in tumor
      suppressor genes, predominantly neurofibromatosis (NF)-1-defective in the
      superficial compartment and tumor protein p53 (TP53)-defective in the deep one,
      with lower proliferation and down-regulation of apoptosis in the latter. TCCs
      follow the general concept of multistep carcinogenesis and proceed through two
      distinct genetic pathways responsible for generating different TCC morphologies.
      These are the inactivation of cyclin-dependent kinase inhibitors (p15, p16, and
      p21WAF/CIP1) in low-grade TCC and early TP53-mediated abnormalities in high-grade
      TCC. TCC progression correlates with genetic instability and accumulation of
      collaborative genetic lesions mainly involving TP53, retinoblastoma (RB)-1, and
      growth factors. Distinctive genetic (low incidence of RB-1 and NF-1
      abnormalities) and kinetic (slower cell turnover) profiles also correlate with a
      "single-file" infiltration pattern and poor survival in muscle-invasive TCCs. The
      underlying molecular changes of carcinoma in situ involve multiple and more
      extensive deletions (normally TP53-defective) than coexistent invasive TCC,
      suggesting an independent genetic evolution, while low-grade dysplasia is mainly
      polyclonal and shows a low rate of gene deletions.

PMID- 11315627
TI  - Subcutaneous lymphoid hyperplasia arising at site of ethnic scarifications and
      mimicking subcutaneous panniculitis-like T-cell lymphoma.
AB  - The case of a 40-year-old black man, who developed a very unusual tumour-like
      lymphoid hyperplasia involving primarily the subcutaneous tissue, is reported.
      The lesion, which arose at a site of tribal scarifications, displayed a deceptive
      morphology that closely resembled subcutaneous panniculitis-like T-cell lymphoma
      (SPTCL). An accurate diagnosis could only be made following detailed
      immunohistochemical and molecular studies. Although SPTCL has been thought to
      represent a very specific clinicopathologic entity, the present case illustrates
      that its histological appearance can, however, be closely mimicked by reactive
      and benign conditions.

PMID- 11315628
TI  - Uterus-like mass in the uterine cervix: superficial cervical endometriosis with
      florid smooth muscle metaplasia?
AB  - This study describes a 47-year-old woman, gravida 2, para 2, with a uterine
      polypoid mass. The 25-mm mass, which was growing into the endocervical canal, had
      a central cavity lined with endometrium and surrounded by smooth muscle layers.
      It strongly resembled a miniature uterus. It is concluded that the mass
      represented superficial cervical endometriosis with florid smooth muscle
      metaplasia of endometrial stromal cells.

PMID- 11315629
TI  - A case of renal involvement in persistent immune activation caused by chlamydial
      salpingitis.
AB  - A 24-year-old woman presented with renal insufficiency, macrohematuria, and mild
      urinary protein. Polyclonal hypergamma-globulinemia, thrombocytosis, increased
      concentration of serum, and urinary interleukin (IL)-6 all indicated persistent
      immune activation caused by a Chlamydia trachomatis infection of the fallopian
      tube. Gynecological treatment with levofloxacin was effective both for the renal
      symptoms and other immunological parameters. First and second renal biopsy
      specimens showed an immune-complex glomerulopathy with extensive interstitial
      infiltration of many types of inflammatory cells, including plasma cells. Thus,
      we conclude that chlamydial salpingitis must be considered as one causative
      disease factor for renal involvement by means of its persistent immune activation
      effects.

PMID- 11315630
TI  - Intraductal acinar cell carcinoma of the pancreas.
AB  - We describe a purely intraductal acinar cell carcinoma involving branch ducts of
      the pancreas in a 74-year-old man, which presented as recurrent episodes of acute
      pancreatitis. Endoscopic ultrasound examination revealed an intraductal mass
      bulging into the main pancreatic duct suggesting, pre-operatively, an intraductal
      mucinous papillary tumour. Gross examination showed several dilated branch ducts
      that contained haemorrhagic tumour material without any solid or true cystic
      formation within the pancreatic parenchyma. Using histology, a purely intraductal
      acinar cell carcinoma was observed, involving branch ducts only, associated with
      foci of carcinoma in situ in adjacent exocrine parenchyma. The main pancreatic
      duct was free of disease except for its communication with a cancerous branch
      duct. A concomitant neuroendocrine microadenoma was incidentally found during
      slide screening. Immunohistochemistry performed on the intraductal proliferation
      confirmed zymogen secretion with positive staining for alpha-1 anti-chymotrypsin
      and anti-trypsin and the persistence of diastase-periodic acid-Schiff positive
      granules in the apical pole of the tumour cells. Neuroendocrine markers were
      negative in the acinar cell carcinoma and positive in the neuroendocrine
      microadenoma. To our knowledge, this is the first report of an intraductal acinar
      cell carcinoma of the pancreas involving branch ducts and sparing the main
      pancreatic duct.

PMID- 11315631
TI  - Iatrogenic implantation of malignant meningioma to the abdominal wall.
AB  - We report a case of malignant meningioma that occurred in the abdominal operation
      scar of a 71-year-old woman. This tumor was a 13 x 8 cm gray-tan soft tumor,
      consisting of multiple nodules. Histologically, tumor cells proliferated in the
      subcutaneous tissue, displaying mostly a storiform pattern and a focal whorl
      formation with high mitotic figures. The immunohistochemical positivity for
      epithelial membrane antigen and negativity for CD34 enabled us to differentiate
      this tumor from a dermatofibroma protuberance or hemangiopericytoma. The patient
      had a history of operation for a recurrent orbital lesion of a malignant
      meningioma that initially developed in the frontal skull base. The present case
      probably resulted from iatrogenic transplantation of the orbital malignant
      meningioma to the lower abdominal wall, which had served as a donor site for
      adipose tissue used to pack the orbital defect.

PMID- 11315632
TI  - Adaptation of wild-type measles virus to CD46 receptor usage.
AB  - Vaccine strains of measles virus (MV) use CD46 as receptor and downregulate CD46
      from the surface of infected cells. MVs isolated and passaged on B-lymphoid cells
      (wild-type MVs) seem to use another receptor and do not downregulate CD46. In the
      present study, we found that isolation of MV on human or marmoset B-lymphoid
      cells did not alter the MV haemagglutinin (H) protein relative to that in the
      patient. The wild-type isolates were adapted to the human epithelial HEp-2 cell
      line or the monkey fibroblast Vero cell line. All HEp-2 cell adapted viruses and
      1 out of 4 Vero cell adapted viruses acquired the capacity to use CD46 as
      receptor, as measured by their ability to infect murine cells expressing human
      CD46. Adaptation to CD46 receptor usage was coupled to substitution of amino acid
      481 of the MV H protein from asparagine to tyrosine but not to CD46
      downregulation. The present study demonstrates that CD46 receptor usage can be
      induced by adaptation of wild-type MV to cells that do not express a wild-type
      receptor and suggests that a similar mechanism acted on the progenitor viruses of
      the present MV vaccine strains during their isolation and attenuation.

PMID- 11315633
TI  - Complete nucleotide sequence of Sesbania mosaic virus: a new virus species of the
      genus Sobemovirus.
AB  - The complete nucleotide sequence of the Sesbania mosaic virus (SeMV) genomic RNA
      was determined by sequencing overlapping cDNA clones. The SeMV genome is 4149
      nucleotides in length and encodes four potential overlapping open reading frames
      (ORFs). Comparison of the nucleotide sequence and the deduced amino acid sequence
      of the four ORFs of SeMV with that of other sobemoviruses revealed that SeMV was
      closest to southern bean mosaic virus Arkansas isolate (SBMV-Ark, 73% identity).
      The 5' non-coding regions of SeMV, SBMV and southern cowpea mosaic virus (SCPMV)
      are nearly identical. However ORF1 of SeMV which encodes for a putative movement
      protein of M(r) 18370 has only 34% identity with SBMV-Ark. ORF 2 encodes a
      polyprotein containing the serine protease, genome linked viral protein (VPg) and
      RNA dependent RNA polymerase domains and shows 78% identity with SBMV-Ark. The N
      terminal amino acid sequence of VPg was found to be TLPPELSIIEIP, which mapped to
      the region 326-337 of ORF2 product and the cleavage site between the protease
      domain and VPg was identified to be E325-T326. The cleavage site between VPg and
      RNA dependent RNA polymerase was predicted to be E445-T446 based on the amino
      acid sequence analysis of the polyprotein from different sobemoviruses. ORF3 is
      nested within ORF2 in a--1 reading frame. The potential ribosomal frame shift
      signal and the downstream stem-loop structure found in other sobemoviruses are
      also conserved in SeMV RNA sequence, indicating that ORF3 might be expressed via-
      1 frame shifting mechanism. ORF4 encodes the coat protein of SeMV, which shows 76
      and 66% identity with SBMV-Ark and SCPMV, respectively. Thus the comparison of
      the non-coding regions and the ORFs of SeMV with other sobemoviruses clearly
      revealed that it is not a strain of SBMV. Phylogenetic analysis of six different
      sobemoviruses, including SeMV, suggests that recombination event is not frequent
      in this group and that SeMV is a distinct member of the genus sobemovirus. The
      analysis also shows sobemoviruses infecting monocotyledons and dicotyledons fall
      into two distinct clusters.

PMID- 11315634
TI  - Nucleotide sequence of a Dianthovirus RNA1-like RNA found in grassy stunt
      diseased rice plants.
AB  - A Dianthovirus RNA1-like RNA (DR1L RNA, 4486 nucleotides in length) was found in
      grassy stunt-diseased rice plants together with Rice grassy stunt virus (RGSV).
      DR1L RNA has characteristics common to Dianthovirus RNA1 such as (1) presence of
      a GGAUUUUUAG potential shifty-heptanucleotide at the end of the 5'-proximal ORF,
      which encodes a 35-kDa protein, followed by a 77-nucleotide sequence capable of
      forming a stem-loop structure for an efficient--1 frameshift to express the
      downstream region in a 96-kDa putative replicase protein, (2) presence of nearly
      identical 17-nucleotide sequences in the 5'-terminal region and in a region
      upstream of an ORF encoding a 28-kDa, putative capsid protein (CP), and (3) near
      identity of the 3'-terminal 20 nucleotides to those of Dianthovirus RNAs. Western
      blot analysis using an antiserum against the C-terminal domain of the putative CP
      and RT-PCR analysis using primers specific to DR1L RNA of fractions after sucrose
      density gradient centrifugation of RGSV nucleoproteins indicated that DR1L RNA is
      associated with the 28-kDa putative CP but not with the 36-kDa RGSV CP. Two
      additional ORFs for 15-kDa and 33-kDa proteins were present in DR1L RNA although
      their expression in plants and functions are not known.

PMID- 11315635
TI  - Effect of IFN-gamma receptor gene deletion on vaccinia virus virulence.
AB  - Two vaccina virus (VV) strains, WR and Praha, were selected for a study
      undertaken to determine whether the virus-encoded interferon-gamma receptor (IFN
      gamma R) plays any role in virus virulence. Both of the viruses expressed the B8R
      gene coding for IFN-gamma R in infected cell cultures. The nucleotide sequence of
      the Praha virus B8R gene was determined, and, when compared with the published
      sequence of the WR virus, it only displayed one silent nucleotide substitution.
      Mutants of the WR and Praha viruses with deleted B8R gene were constructed. In
      rabbits, skin lesions produced by the WR B8R-deleted mutants were smaller and
      tended to disappear earlier than those caused by wild-type WR virus. Similar
      results were obtained with both independently prepared WR B8R-deleted mutants.
      These data strongly suggested that the product of B8R gene did play a role in
      virus virulence. A similar comparison of the wild-type Praha virus and its mutant
      could not be done because of the very low virulence of the parental virus for
      rabbits.

PMID- 11315636
TI  - Involvement of vacuolar proton ATPase in Junin virus multiplication.
AB  - The role of vacuolar-proton ATPase (V-H+ ATPAse) on Junin virus (JV) replication
      was evaluated by analyzing the effect of specific inhibitors of the enzyme
      activity on different steps of virus multiplication cycle. The presence of the
      macrolide antibiotics bafilomycin A1 and concanamycin A during the first two
      hours of infection caused a significant reduction of extracellular infectious
      virus production and viral protein expression in Vero and BHK-21 cells. The
      inhibitory action of the compounds was mainly exerted at an early stage of the JV
      multiplication cycle, without affecting virus attachment to the cell but
      preventing virus penetration. A correlation between the inhibitory action of the
      compounds on intracellular compartments acidification and the reduction of JV
      yield was observed. The addition of concanamycin A at different times after
      infection indicated that the compound also interferes with the release of
      infectious particles to the extracellular medium. Although, intracellular
      transport of JV glycoproteins to the cell membrane, seems not to be affected as
      revealed by immunofluorescence staining. The results confirm that JV enters into
      the cell through the endocytic pathway as previously suggested by using
      lysosomotropic compounds.

PMID- 11315637
TI  - Identification and characterization of a novel tospovirus species using a new RT
      PCR approach.
AB  - A novel tospovirus serologically distinct from all established tospovirus species
      was found in Thailand in Physalis minima L. The S RNA of this virus was cloned by
      a new RT-PCR approach revealing a nucleotide sequence of 3257 nucleotides. The
      ambisense RNA segment encoded a nonstructural protein (NSs) of 469 amino acids,
      with a predicted Mr of 53.2 kDa, and a nucleoprotein (N) of 279 amino acids and a
      Mr of 31.0 kDa, so far the largest N protein known for any tospovirus species. N
      protein sequence comparisons revealed closet relationship to the species
      Watermelon bud necrosis virus (58% identity), Watermelon silver mottle virus and
      Peanut bud necrosis virus (57%) and a distant relationship to Peanut yellow spot
      virus (23%) and Peanut chlorotic fanspot virus (22%).

PMID- 11315638
TI  - Sequence variations of hepatitis B virus promoter regions in persistently
      infected patients.
AB  - The HBV in the sera of two chronic active hepatitis patients were analyzed for
      the promoter sequence heterogeneity. In most cases, the proportion of any
      particular clone in the total viral populations was less than 50%, showing high
      mutation rates. In contrast, promoter sequences of HBV from asymptomatic carriers
      revealed only a few point mutations with no deletions. HBV in chronic patient
      harbored variants with multiple mutations throughout promoters including 1762 (A
      to-T), 1764 (G-to-A) double mutation in C promoter and deletions near CCAAT site
      in S promoter. Unlike other three promoter regions, C, pre-S1 and S, of HBV which
      revealed a high level of sequence heterogeneity, the X promoter region (from
      nt985 to 1430) showed little sequence heterogeneity within a patient. However,
      the predominant viral clones in two patients were quite different from each
      other. In addition to mutations in promoter regions, a deletion mutation in the
      translation start codon was also found in pre-S1 gene. The results in this report
      indicate that the mutation rates are not the same in all four promoters and that
      one of the strategies for maintaining persistent infection could be through
      mutations in viral promoters which then impair the balance of viral gene
      expressions.

PMID- 11315639
TI  - Immune responses and protection induced by mucosal and systemic immunisation with
      recombinant measles nucleoprotein in a mouse model of measles virus-induced
      encephalitis.
AB  - In this study the immunogenicity of recombinant nucleoprotein (Np) administered
      intranasally or intraperitoneally, and its ability to support a systemic
      protective anti-virus antibody response was examined, in a mouse model of measles
      virus (MV)-induced encephalitis. Although both intranasal and intraperitoneal
      routes of immunisation resulted in priming Np- and MV-specific T-cell responses,
      the intraperitoneal route was shown to prime for a predominantly IgG2a serum anti
      MV antibody response of high avidity, which confered complete protection
      following intracranial challenge with a neuroadapted strain of MV. On the other
      hand, intranasal priming resulted in a mixed IgG1, IgG2a serum anti-MV antibody
      response of low avidity, and only 43% of immunised mice survived following
      intracranial challenge with the neuroadapted strain of MV. These findings suggest
      that the route of immunisation in combination with an appropriate adjuvant could
      influence the induction of a quality antibody response with protective capacity.

PMID- 11315640
TI  - Identification, transcription and sequence analysis of the Spodoptera littoralis
      nucleopolyhedrovirus (SpliNPV) DNA polymerase gene.
AB  - Sequence analysis of a 6.4 kb DNA region from the Spodoptera littoralis
      multinucleocapsid nucleopolyhedrovirus (SpliNPV) revealed a large open reading
      frame (ORF) encoding a predicted polypeptide of 998 amino acid (aa) residues with
      a molecular mass of 114.93 kDa, located between 47.2-52.3 m.u. on the SpliNPV
      genome. Comparative sequence analyses demonstrated that the ORF encodes a DNA
      polymerase gene (dnapol) that contains conserved exonuclease domains and DNA
      polymerase motifs found in many prokaryotic, eukaryotic, and viral replicative
      DNA polymerases. A second ORF, ORF138, located between the lef-3 and dnapol,
      encodes a 138 aa polypetide that is homologous to ORF66 of the Autographa
      californica MNPV (AcMNPV). SpliNPV DNA polymerase shares an overall aa sequence
      identity of 39% with that of AcMNPV. A 3.0 kb SpliNPV dnapol-specific transcript
      was detected initially at 2 hpi and became abundant 48 hpi by Northern blot
      analysis. The transcription initiation site was mapped to an NPV early promoter
      element, ACGT. 3' RACE demonstrated that the SpliNPV dnapol transcript terminated
      at the polyadenylation signal AATAAA. Sequence analysis suggested that the
      SpliNPV dnapol and the dnapol of the NPV of S. litura (SpltNPV) are closely
      related.

PMID- 11315641
TI  - Murine recombinant prion protein induces ordered aggregation of linear nucleic
      acids to condensed globular structures.
AB  - Interaction between nucleic acid and recombinant murine prion protein, MoPrPC
      resulted in a time-dependent change in the nucleic acid morphology revealed by
      electron microscopy. After the addition of the protein to DNA, association of
      small number of nucleic acid molecules (nucleo-protein complex) was followed by
      aggregation of large number of them still retaining their initial linear
      morphology. With increase in the incubation time, ordered aggregation resulted in
      small condensed spherical globules. Subsequently, the formation of large
      condensed particles took place either by fusion of the already formed small
      globules or by accumulation of more nucleic acid molecules on them. The condensed
      nucleic acid structures observed here were different from other known
      morphologically altered nucleic acid structures induced by different cellular
      proteins. The condensed nucleic acid structures dissociated spontaneously. The
      formation of the prion protein-induced condensed nucleic acid structures
      resembled the human immunodeficiency virus 1 nucleocapsid protein NCp7-induced
      condensed ordered aggregates of nucleic acids. In the latter system, both the
      processes of condensation and dissociation of the nucleoprotein complex are
      believed to be responsible for the functional properties of the HIV-1 virus.
      Demonstration of functional activity of the prion protein-nucleic acid complex
      would be relevant for a role of nucleic acid in prion diseases.

PMID- 11315642
TI  - Structural, biochemical and electrostatic basis of serotype specificity in bovine
      enteroviruses.
AB  - We have performed immunostructural analyses of three closely related
      picornaviruses in order to gain understanding of the biochemical and structural
      basis of serotype specificity. We carried out sequence alignments of the capsid
      regions of three bovine enterovirus strains: VG-5-27 and M-4 from serotype 1 and
      PS-87 from serotype 2. Using our knowledge of the three dimensional and antigenic
      structure of strain VG-5-27 and the high levels of sequence identity between the
      strains, we have calculated the structures and solvent-accessible electrostatic
      potentials of the epitopes of all three viruses. We have demonstrated the
      viability of the molecular models of the epitopes of the M-4 and PS-87 strains.
      In each of the strains, we have explained the serotype specificities in terms of
      specific physical and chemical properties, and identified individual residues
      which are pivotal in determination of antibody recognition. These changes are in
      agreement with the known cross-reactivity of peptide and antiviral sera, showing
      that it is possible to derive structures for short variable sections of proteins
      of high sequence identity using molecular modelling which are significant in
      terms of biological function. We believe this study to be a novel approach in the
      analysis of virus serotype specificity.

PMID- 11315643
TI  - Partial characterisation of citrus leaf blotch virus, a new virus from Nagami
      kumquat.
AB  - Citrus leaf blotch virus (CLBV) was purified from leaves of Nagami kumquat SRA
      153 that showed bud union crease when propagated on Troyer citrange. Virions were
      filamentous particles (960 x 14 nm) containing a 42 kDa protein and a single
      stranded RNA (ssRNA) of about 9,000 nt (Mr 3 x 10(6)). Infected tissue contained
      three species of double-stranded RNA (dsRNA) of Mr 6, 4.5 and 3.4 x 10(6). The
      nucleotide sequence of several complementary DNA (cDNA) clones showed significant
      similarities with replication-related proteins from plant filamentous viruses in
      several genera. A digoxigenin-labelled probe from one of these cDNA clones
      hybridised in Northern blots with ssRNA from virions and with the three dsRNA
      species, suggesting that the ssRNA is the genomic RNA of the virus, the largest
      dsRNA is its replicative form, and the two smaller dsRNAs probably replicative
      forms of 5' co-terminal subgenomic RNAs. CLBV was also detected in several citrus
      cultivars from Spain and Japan including Navelina sweet orange field trees
      propagated on Troyer citrange showing bud union crease; however, no virus could
      be detected in other citrus trees with similar symptoms. This indicates that CLBV
      is not restricted to kumquat SRA-153, but its involvement in causing the bud
      union disorder remains unclear.

PMID- 11315644
TI  - Identification and characterization of mutations in the high growth vaccine
      strain of influenza virus.
AB  - X-31(H3N2) virus, which is a high yielding reassortant between A/PR/8/34(H1N1)
      and A/Aichi/68(H3N2), is currently used as a backbone strain for influenza
      vaccine production. The sequence of the current X-31 virus was determined from
      cloned cDNA of 6 internal RNA genes, and was compared with the original sequence
      of the A/PR/8/34 virus. 71 point mutations were accumulated in the six internal
      viral genes (PB2, PB1, PA, NP, M and NS). These nucleotide changes encode 23
      amino acid substitutions in seven viral proteins (PB2, PB1, PA, M1, M2, NS1 and
      NS2). Among three polymerase genes, a significantly low mutation frequency was
      observed in PA gene as compared to PB2 and PB1. The mutation frequency at the
      nucleotide level was significantly low in NP gene without any amino acid
      substitution, being only about 20% of those observed in 5 other internal genes.
      The unequal distribution of mutations among different viral proteins may
      correlate with individual role of each protein in viral growth.

PMID- 11315645
TI  - Further development of a recombinant feline herpesvirus type 1 expressing the Gag
      protein of feline immunodeficiency virus.
AB  - We have previously reported the construction of a recombinant feline herpesvirus
      type 1 (FHV-1), designated C7301ddlTK-gag, expressing the Gag precursor protein
      of feline immunodeficiency virus (FIV). In this study, we report the construction
      of a further recombinant FHV-1 (ddlTK(gBp)-gag) which carries an FHV-1 gB
      promoter sequence upstream of the FIV gag gene of C7301ddlTK-gag. Strong
      expression of the FIV Gag protein by ddlTK(gBp)-gag was confirmed by immunoblot
      analyses and enzyme-linked immunosorbent assays. Although C7301ddlTK-gag and
      ddlTK(gBp)-gag failed to induce anti-FIV Gag antibodies in cats, we confirmed the
      infectivity and stability of these recombinants in cats.

PMID- 11315646
TI  - Comparison of the S RNA segments among Japanese isolates and Taiwanese isolates
      of Watermelon silver mottle virus.
AB  - The complete nucleotide sequences of the S RNA of two Japanese isolates of
      Watermelon silver mottle virus were determined. One was isolated from naturally
      infected watermelon and causes malformation on upper leaves of Tetragonia
      expansa. The other was isolated from melon and causes characteristic yellow
      necrotic lesions on upper leaves of T. expansa. The total nucleotide sequences of
      the S RNA of WS-O and WS-Y were 3553 nt and 3558 nt long, respectively. Both the
      nucleotide sequences and the deduced amino acid sequences of WS-O and WS-Y were
      quite similar even though the symptoms on T. expansa are quite different. They
      were also significantly similar to those of the Taiwanese isolates, Topso-W and
      Tospo-To. These results suggested that the Japanese isolates and the Taiwanese
      isolates of WSMoV were classified as one group not only serologically but also
      genetically. Within the S RNA sequences, the most variable region was the
      intergenic region between the N gene and the NSs gene. This was due to a 20 nt
      insertion between the Japanese isolates and the Taiwanese isolates.

PMID- 11315647
TI  - Complete nucleotide sequence of cherry necrotic rusty mottle virus.
AB  - A virus closely related to cherry green ring mottle virus (CGRMV) was isolated
      from a tree displaying typical symptoms of cherry necrotic rusty mottle disease.
      We have named this virus cherry necrotic rusty mottle virus (CNRMV) and report
      here its complete genomic sequence as determined from overlapping cloned cDNAs.
      CNRMV has a genome of 8,432 nucleotides excluding the 3' poly(A) sequence and
      codes for 7 significant open reading frames (ORFs). Five of these ORFs are
      conserved among all fovea-, allexi-, potex- and carlaviruses and code for a
      methyltransferase/helicase/polymerase polypeptide, the triple gene block movement
      proteins and the coat protein. Two further ORFs, ORFs 2a and 5a, are nested
      completely within ORFs 2 and 5, respectively. The putative translation products
      from these ORFs display sequence similarity with putative translation products
      from two similarly nested ORFs present in the CGRMV genome. The function of these
      two ORFs is unknown, nor are they conserved among other related viruses.

PMID- 11315648
TI  - Characterization of Kaposi's sarcoma-associated herpesvirus/human herpesvirus-8
      ORF57 promoter.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) is a recently discovered human
      gamma herpesvirus (HHV-8) that plays an important role in Kaposi's sarcoma
      development. Here, we further characterize the regulation of the early HHV-8
      gene, open reading frame 57 (ORF57). ORF57 is a spliced gene consisting of two
      exons with a 108-bp intron near the 5' end. The ORF57 mRNA can potentially be
      initiated at two different start sites, and its expression can be significantly
      stimulated by ORF50, an HHV-8 immediate early gene. The target site for ORF50
      transactivation was mapped to a 40-bp fragment compassing nt 81904 to 81943 in
      the ORF57 promoter. Our study on the regulation of ORF57 expression by ORF50
      provides the basis for further studies on the regulation of HHV-8 lytic gene
      expression.

PMID- 11315649
TI  - Computerized densitometric measurement system (CDMS) for the quantitative
      analysis of diffuse retinal nerve fiber layer atrophy.
AB  - Since observable retinal nerve fiber layer (RNFL) atrophy occures several years
      before irreversible glaucomatous visual field damage in glaucoma patients,
      quantitative assessment of the diffuse RNFL atrophy has been the goal of many
      research efforts. The loss of RNFL reflectance is informative sign of the diffuse
      RNFL atrophy, and appears in monochrome photograph of RNFL. We have, therefore,
      made a system by which we could measure the loss of RNFL reflectance and named it
      Computerized Densitometric Measurement System (CDMS). In this method, density
      profiles concentric with optical disc are extracted from the digitalized RNFL
      photograph. Density integral of superior and inferior segments in the density
      profile is used for the assessment of RNFL atrophy. Satisfactory results were
      obtained about the clinical utility of this method when the CDMS measurement was
      compared with the indicator of loss of visual function. Intra- and inter-operator
      reproducibility was also excellent.

PMID- 11315650
TI  - Handcycling: different modes and gear ratios.
AB  - Handrim wheelchair propulsion is a straining form of ambulation. In contrast, arm
      crank exercise in laboratory settings has shown a higher degree of gross
      mechanical efficiency and increased levels of peak power output. Moreover, arm
      crank exercise can be conducted at different gear ratios and in asynchronic or
      synchronic mode. Although tricycle crank exercise or handcycling has become
      increasingly popular for recreational use, sports and outdoor wheeling over the
      last decade, today little is known about the cardiopulmonary strain in
      handcycling. The physiological and subjective responses during handcycling were
      evaluated in a group of 12 male non-wheelchair users (age 24.6 +/- 2.7 yr; body
      weight 73.7 +/- 9.7 kg). During an incremental submaximal exercise test on a
      motor driven treadmill (velocity: 1.8 ms-1; an incremental slope of 1% per 3 min;
      0-3%; mean power output of the subject group varied between 7.6 +/- 1.6 W and
      47.5 +/- 6.2 W), effects of asynchronic and synchronic crank settings and three
      different gear ratios (1:0.42, 1:0.59, 1:0.74 (or 24, 36 and 44 rpm)) were
      evaluated in a random testing sequence. Significantly lower levels of mean oxygen
      uptake, ventilation, relative heart rate and oxygen uptake were seen during
      synchronic arm use and for the lighter gear ratios (i.e. higher movement
      frequency; 44 rpm). Subjective local perceived discomfort showed similar trends.
      Conversely, gross mechanical efficiency appeared higher for these conditions. The
      need for strong medio-lateral stabilizing muscle effort during asynchronic arm
      use (to ensure a proper wheeling direction as well as simultaneous power transfer
      to the cranks) and the effective use of the trunk in this subject group may
      explain the advantage of synchronic arm use. Whether this advantage is
      consolidated among wheelchair confined individuals needs further study. Apart
      from the important effects of a shift in force--velocity characteristics of the
      contracting muscles with varying gear ratios, increased static finger flexor and
      arm muscle activity may explain the increased strain in the somewhat unnatural
      heavy gear condition (24 rpm) at the studied velocity. Results need to be re
      evaluated for wheelchair user populations and different higher velocities and
      power conditions. Moreover, other aspects of the wheelchair--user interface must
      be studied in order to generate optimum fitting and design guidelines for
      different user groups and conditions of use.

PMID- 11315651
TI  - A multi-purpose rehabilitation frame: an apparatus for experimental
      investigations of human balance and postural control.
AB  - Moving and rotating platforms are often used in experimental investigations of
      human balance and postural control. These devices are not well suited for testing
      elderly and neurologically impaired individuals, because of inherent risk of
      injury to the experimental subject due to a potential fall. This paper describes
      a novel mechanical apparatus that generates perturbations to a standing subject
      by applying pushing forces at the level of the pelvis and can also provide
      restoring forces in the case of destabilization. The device has two degrees of
      freedom, which are actuated by hydraulic servo systems, and can deliver a
      perturbation in any direction comprised within anterio-posterior and medio
      lateral postural space. The accuracy and repeatability of the perturbations
      elicited in eight different directions was evaluated. The results, showing a high
      degree of correlation between the trajectories in both degrees of freedom of the
      apparatus, demonstrate that accurate and repeatable perturbations can be imposed
      on the subjects tested.

PMID- 11315652
TI  - Mesh-independent prediction of skin burns injury.
AB  - This paper presents a robust finite element model (FEM) with multiple-layers of
      varying properties for investigation of burn effects on human skin during a
      burning process resulting from exposure of skin surface to a contact heat source
      and a hot moving fluid. Henriques' theory of skin burns is used in conjunction
      with two-dimensional Pennes bioheat transfer equation for determining the spatial
      and temporal extent of burn injury. The model developed is a two-dimensional
      axisymmetric model in cylindrical coordinates. The various tissue layers account
      for changing thermal properties with respect to skin anatomy. A finite element
      scheme that uses the backward Euler method is used to solve the problem. The
      injury processes of skin subsequent to the removal of the heat source (post-burn)
      will also be inspected. The mesh employed in this model consists of a high
      density of nodes and elements in which a thorough mesh convergence study was
      done. A comparison of the transient temperature field computed by this model
      against Diller's results using the FE technique with a comparatively coarse mesh
      of 125 elements and experimental data by Orgill et al. has been done in the
      present study. It concluded that improved accurate solutions have been performed
      using the robust model developed due to the achievement of a mesh-independent
      solution.

PMID- 11315653
TI  - Application of orthogonal neural network to craniomaxillary reconstruction.
AB  - Traditionally, the orthopaedist, according to their past experience, reconstructs
      damaged area while the operation is in progress. This may prolong the operation
      and cause the wound to become infected. Most importantly it is difficult to
      precisely match the skeletal defect. A well-disciplined network of prediction re
      fabricates the damaged area through automation. This research is based on the CT
      image file, which is the product of X-ray computed tomography (CT), and computes
      the skeletal positions around the damaged area through image processing and
      boundary detection. The skeletal positions are inputted into the orthogonal
      neural network and discipline the network so that it possesses the scattering
      characteristic of bone. The network then calculates skeletal positions in the
      damaged area and revises the former CT image file to rebuild a 3D model.
      Accordingly, in comparison with a manual sketch, the orthogonal neural network
      forecast is more geometrically precise. Moreover, the forecast satisfies the
      second order derivative, which is a continuous function, and the edge of the
      fabricated bone is therefore kept smoother.

PMID- 11315654
TI  - Stress analysis of different wall thicknesses of implant fixture with various
      boundary levels.
AB  - The aim of the present work is to develop 3D finite element models of implant
      fixture with different wall thicknesses to predict maximum stress concentration
      sites and distribution contours after loading. A maximum lateral force of 150 N
      was applied to simulate horizontal occlusal forces. When the fixtures were
      constrained to simulate different boundary levels, the maximum equivalent stress
      (max EQV) was always located at the implant-bone interface. Max EQV increased
      when the wall thickness or boundary level was reduced to a certain extent. The
      fixture with a wall thickness of 0.97 mm demonstrated the smallest stress
      increase ratio when the boundary level was lowered. Our results indicated that
      both wall thickness and the boundary level played important roles in maintaining
      a well-distributed stress level within the fixture. The stress concentration
      decreased when the fixture wall became thicker, however, this effect was less
      significant when the surrounding bone level was reduced.

PMID- 11315655
TI  - Measurement of rotary pump flow and pressure by computation of driving motor
      power and speed.
AB  - Measurement of pump flow and pressure by ventricular assist is an important
      process, but difficult to achieve. On one hand, the pump flow and pressure are
      indicators of pump performance and the physiologic status of the receptor,
      meanwhile providing a control basis of the blood pump itself. On the other hand,
      the direct measurement forces the receptor to connect with a flow meter and a
      manometer, and the sensors of these meters may cause haematological problems and
      increase the danger of infection. A novel method for measuring flow rate and
      pressure of rotary pump has been developed recently. First the pump performs at
      several rotating speeds, and at each speed the flow rate, pump head and the motor
      power (voltage x current) are recorded and shown in diagrams, thus obtaining P
      (motor power)-Q (pump volume) curves as well as P-H (pump head) curves. Secondly,
      the P, n (rotating speed) values are loaded into the input layer of a 3-layer BP
      (back propagation) neural network and the Q and H values into the output layer,
      to convert P-Q and P-H relations into Q = f (P,n) and H = g (P, n) functions.
      Thirdly, these functions are stored by computer to establish a database as an
      archive of this pump. Finally, the pump flow and pressure can be computed from
      motor power and speed during animal experiments or clinical trials. This new
      method was used in the authors' impeller pump. The results demonstrated that the
      error for pump head was less than 2% and that for pump flow was under 5%, so its
      accuracy is better than that of non-invasive measuring methods.

PMID- 11315656
TI  - Skin tensile strength modulation by compressive garments in burn patients. A
      pilot study.
AB  - Compression therapy is frequently used to prevent hypertrophy of post-burn scars.
      This pilot study was performed in 6 patients to assess non-invasive changes
      induced in the tensile strength of the skin before any clinical improvement can
      be perceived. Assessments were performed using a computerized suction device
      delivering three 5 s cycles of 500 mbar depression. Measurements were made at one
      month intervals for three months after initiating the garment compression
      therapy. Comparisons were made between the intact skin, the ungrafted and grafted
      post-burn scars and the graft donor sites. Data show that garment compression
      therapy alters the tensile strength in the skin of all test sites. The most
      reliable variations consist of an increase in both the extensibility and
      elasticity of the tissues submitted to traction.

PMID- 11315657
TI  - Varying the importance of a prospective memory task: differential effects across
      time- and event-based prospective memory.
AB  - Only few studies have addressed the issue of task importance in prospective
      memory. Most of them, but not all, have shown that perceived task importance does
      improve prospective memory performance. However, there is little understanding of
      (1) the conditions under which importance of the prospective memory task makes a
      difference in performance and (2) the mechanisms by which perceived task
      importance has an effect on prospective memory performance. The present study
      reports two experiments that manipulate task importance in a time-based and an
      event-based prospective memory paradigm. Results show that importance has an
      effect on the time-based but not on the event-based task. Further analyses of the
      performance in the cover tasks as well as the monitoring behaviour indicate that
      importance improves prospective memory to the degree the task requires the
      strategic allocation of attentional resources.

PMID- 11315658
TI  - Complexity effects in visuo-spatial working memory: implications for the role of
      long-term memory.
AB  - Several studies have shown that the capacity of visuo-spatial working memory is
      limited by complexity. Using a variant of the Corsi blocks task, this paper
      investigates the effect of complexity of the to-be-remembered path on visuo
      spatial memory span. Redundancy was determined by three Gestalt principles:
      symmetry, repetition, and continuation. Experiment 1 revealed an effect of path
      complexity. The subsequent experiments explored whether the superiority for
      recall of structured over complex paths can be attributed solely to the operation
      of visuo-spatial working memory, or whether it also reflects the use of long-term
      knowledge. Experiment 2 demonstrated that the effect of complexity remained, even
      when the mechanisms for visuo-spatial coding were removed by a secondary visuo
      spatial task. In Experiments 3 and 4 subjects were trained in the recall of
      complex paths. This led to the creation of long-term memory representations for
      these paths, as shown by an improvement in their span, and a concomitant lack of
      transfer to new paths. Finally, Experiment 5 showed that one prior repetition of
      a complex path was sufficient to produce specific and long-term learning effects.
      These results point to the involvement of long-term memory processes in the
      temporary retention of visuo-spatial material for which representations exist in
      long-term memory. They also suggest that the effect of complexity may provide a
      tractable technique for investigating the mechanisms underlying the limits of
      visuo-spatial short-term storage.

PMID- 11315659
TI  - Contextual dependencies in predictive learning.
AB  - Two experiments assessed contextual dependencies in a predictive-learning task.
      Subjects learned to associate each of four pictorial stimuli with the occurrence
      or non-occurrence of a specific outcome. Each of these stimuli, the intentional
      stimuli, was presented against one of two different visual (Experiment 1) or
      auditory (Experiment 2) context stimuli. These context stimuli were incidental:
      subjects were not explicitly instructed to pay any attention to them and each of
      them in isolation was not predictive of the outcome. During acquisition and
      testing, subjects expressed the expected relationship between intentional
      stimulus and outcome by an appropriate key press. At test, intentional stimuli
      were presented either with the same contextual stimulus as also present during
      acquisition (same trials), or with the other one (switched trials). The response
      latency was slower on switched trials than on same trials in each experiment, a
      result extending previous findings on the effect of environmental contextual
      stimuli on task performance. Results are discussed in the framework of contextual
      occasion setting and habituation to contextual stimuli.

PMID- 11315660
TI  - Output monitoring tests reveal false memories of memories that never existed.
AB  - Three experiments were conducted to assess participants' beliefs about potential
      false memories that might have occurred during free recall tests. An input-output
      monitoring test was administered that required participants to discriminate
      between items that were studied and recalled, studied and not recalled, or were
      entirely new. Critical lures from Roediger and McDermott's (1995) paradigm were
      inserted into this test. The results demonstrated that participants believed
      erroneously recalled items were both studied and recalled. The intriguing finding
      was that unrecalled items were believed to have been studied approximately 80% of
      the time, and half of those were also believed to have been recalled. This result
      represents a dual false memory effect in which items were believed to have been
      studied and also to have been recalled. The ramifications of this new procedure
      are discussed in terms of proposed experiments that might clarify the genesis of
      these false memories.

PMID- 11315661
TI  - Assessing the effectiveness of warnings and the phenomenological characteristics
      of false memories.
AB  - The phenomenology of false memories was investigated in three experiments in
      which participants heard two experimenters read lists of items that were related
      to critical nonpresented items. In Experiments 1, following a recognition memory
      test, participants rated the phenomenological characteristics of their memories
      immediately and after a 48-hour delay. False recognition was prevalent and on
      several dimensions participants rated their true memories as more vivid than
      their false memories. In Experiments 2 and 3, following the study phase,
      participants were warned about the phenomenological differences between true and
      false memories and were instructed to use this information to avoid reporting
      nonpresented items. This type of warning was ineffective at reducing false recall
      (Experiment 2) and false recognition (Experiment 3) relative to unwarned
      participants. Importantly, the inability of explicit warnings to impact illusory
      recollections demonstrates that the false memories cannot be attributed simply to
      a criterion shift.

PMID- 11315662
TI  - [Hygiene of children and adolescents is a leading system-forming component of the
      medical prevention specialty].

PMID- 11315663
TI  - [Hygienic and ecological criteria of hazards in the protection of aqueous biota].
AB  - Man is not always sensitive to toxic agents than the representative of the
      aqueous biota. Almost in every fifth case, human sensitivity to water pollutants
      is higher and that to a number of compounds is more than 100 times greater.
      Therefore, there cannot be unified environmental and hygienic standards and
      fishery and sanitary MAC of water agents should be taken apart to provide a
      reliable safety of human water consumption.

PMID- 11315664
TI  - [General and oncologic morbidity in Moscow municipal transport drivers].
AB  - A case study was undertaken to examine general and cancer mortality rates and
      cancer morbidity among municipal transport drivers in Moscow. The mortality and
      cancer morbidity in 1969 to 1988 were followed up among 2528 men and 212 women.
      In this period, male mortality rates due to malignant neoplasms, cardiovascular
      diseases and all causes taken together were statistically lower than the expected
      rates. Male cancer morbidity rates were also lower the expected ones. In the past
      decade 42 cases of gastric cancer were revealed in the cohort, which was
      statistically greater than the expected figures (29.8). In the first decade,
      prostatic cancer mortality was statistically significantly higher in bus drivers
      with length of service of over 20 years. Among women, there were only 12 deaths,
      with significantly decreased mortality rates. Esophageal cancer was detected in
      women who had worked as drivers for 20-29 years. The lower morbidity and
      mortality rates may be associated with the "healthy worker effect", i.e. with the
      fact that staff is strictly selected for this job.

PMID- 11315665
TI  - [Indices of physical development of the male population of a Siberian town].
AB  - Data on the physical development of the present-day male population are given. In
      depth anthropometric study using the methods calculating the fractionation of the
      body's composition, graded exercise functional tests provided morphofunctional
      characteristics of males with regard for an ontogenetic aspect. It also showed
      that there were common biological regularities of their development.

PMID- 11315666
TI  - [Evaluating the risks of the effects of benzene-polluted air on human health].

PMID- 11315667
TI  - [Role of the General Hygiene Department of the I.M. Sechenov Moscow Medical
      Academy in the development of scientific and methodological bases of preventive
      medicine].

PMID- 11315668
TI  - [The Epidemiology Department of the I.M. Sechenov Moscow Medical Academy].

PMID- 11315669
TI  - [Characteristic of mutants of Pseudomonas putida IPM-36 recombinant strains,
      selected by anticipating growth on a media containing an inducer of cry3A gene
      expression].
AB  - Induction of the expression of the delta-endotoxin gene from Bacillus
      thuringiensis var. tenebrionis in the recombinant strain Pseudomonas putida IPM
      36 negatively affected the viability and the growth rate of the culture. In order
      to optimize the insecticide production by the recombinant strain, mutant clones
      exhibiting anticipating growth on an inducer-containing medium were selected and
      studied. These clones differed in such aspects as the localization of mutations
      (either in plasmid pBTN11, carrying the cry3A gene, or in the chromosome), growth
      rate, or the level of delta-endotoxin synthesis after induction. Several mutants
      obtained proved much superior to P. putida IPM-36 in their structural and
      segregation stability, although they were as efficient as the original strain
      with respect to the production of the insecticide (protei Cry3A).

PMID- 11315670
TI  - [Isolation and study of Acinetobacter sp. mutant strains defective in production
      of exopolysaccharides].
AB  - Nitrosoguanidine-induced mutants of Acinetobacter sp. defective in
      exopolysaccharide biosynthesis did not differ from the parent strain in
      distinguishing physiological and biochemical properties, such as requirements for
      growth factors, utilization of mono- and disaccharides, and resistance to
      antibiotics. The genetic relation of parent and mutant strains was shown by 16S
      rRNA PCR analysis. The comparative study of parent and mutant strains with
      respect to resistance to unfavorable environmental factors confirmed our
      hypothesis that Acinetobacter sp. exopolysaccharides perform protective
      functions. Hybridization experiments revealed the conjugal transfer of plasmid
      R68.45 from Pseudomonas putida BS228 (R68.45) to mutant but not to the parent
      Acinetobacter sp. strains. The role of the Acinetobacter sp. exopolysaccharides
      in providing the genetic stability of this bacterium is discussed.

PMID- 11315671
TI  - [Genetic transformation of Bacillus subtilis cells in the presence of clay
      minerals montmorillonite and kaolinite].
AB  - The effect of the clay minerals montmorillonite and kaolinite on the
      transformation of competent Bacillus subtilis cells with chromosomal DNA was
      studied. Clay particles were found to substantially increase the transformation
      frequency of competent cells, as well as the rate of their spontaneous
      chromosomal and plasmid transformation. The effect was ascribed to the adsorption
      of bacterial cells on the surface of mineral particles.

PMID- 11315672
TI  - [Establishment of the phylogenetic relationship between the microbial producers
      of cyclodextrin glucanotransferases using their complete amino acid sequences].
AB  - A phylogenetic tree was constructed on the basis of the amino acid sequences of
      the known cyclodextrin glucanotransferases (CDGTs), including those deduced from
      the nucleotide sequences of Bacillus sp. strain 6.6.3 and Paenibacillus macerans
      IB-7 genes encoding alpha- and beta-CDGTs. The tree clearly demonstrates the
      existence of distinct phylogenetic groups of CDGT-producing microorganisms and
      the divergence of the alpha-, beta-, and gamma-CDGT produced by microorganisms
      from the genera Bacillus, Paenibacillus, Brevibacillus, and Thermoanaerobacter
      from a common ancestor, whereas the CDGT of Klebsiella pneumoniae is independent
      and results from the convergence of different ancestors. The degree of homology
      of the leader peptide sequences of CDGTs may serve as a criterion of intraspecies
      relatedness between CDGT-producing microorganisms.

PMID- 11315673
TI  - [Clusterization of halophilic and halotolerant eubacteria using whole-cell
      protein electrophoresis data].
AB  - Total cell proteins of the nineteen halophilic and halotolerant eubacteria
      isolated from marine sediments and highly mineralized formation waters of oil
      fields were investigated by SDS gel electrophoresis. The microorganisms studied,
      phenotypically identified as belonging to the genera Dietzia, Rhodococcus,
      Staphylococcus, Cytophaga, Brevibacterium, and Archangium, were found to form
      clearly distinguishable clusters (20-30% similarity at the generic level) on the
      dendrogram derived from electrophoretic protein patterns. Protein similarity data
      confirmed the heterogeneity of Rhodococcus maris and its relatedness to the genus
      Dietza.

PMID- 11315674
TI  - [Taxonomic study of five streptomycete species with synonymous names from the ISP
      collection].
AB  - The taxonomic investigation of five streptomycete species with synonymous names
      from the International Streptomyces Project (ISP) collection was carried out
      using the methods of population analysis, DNA-DNA hybridization, and multilocus
      DNA fingerprinting. Only two species with synonymous names, S. alboviridis ISP
      5326 and S. oligocarbophilus ISP 5589, were found to be actually identical. Three
      other species investigated, S. krainskii ISP 5321, S. craterifer ISP 5296, and S.
      anulatus ISP 5361, whose names are usually referred to as synonymous, were shown
      to be different species.

PMID- 11315675
TI  - [A novel plant-associated thermotolerant alkalophilic methylotroph of the genus
      Paracoccus].
AB  - Strain GB isolated from the maize rhizosphere is a gram-negative, aerobic, non
      spore-forming, nonpigmented, nonmotile, chemolithotrophic, facultatively
      methylotrophic bacterium. Cells are cocci or short rods. The strain does not
      require vitamins. Optimum growth in a medium with methanol occurs at 38-42
      degrees C at pH 8.0-9.2. The doubling time is 12 h. In addition to methanol, the
      bacterium can grow on methylamine, dimethylformamide, acetone, thiosulfate +
      NaHCO3, and in an atmosphere of H2 + CO2 + O2. Methanol and methylamine are
      oxidized by the respective dehydrogenases to CO2 via formaldehyde and formate,
      respectively. The CO2 produced is assimilated via the ribulose bisphosphate
      pathway. Fatty acids are dominated by cyclopropanoic (58-61%), palmitic (24-26%),
      and octadecanoic (8-9%) acids. The main phospholipids are phosphatidylglycerol,
      phosphatidylethanolamine, and phosphatidylcholine. The major ubiquinone is Q10.
      The bacterial genome contains genes controlling the synthesis and secretion of
      cytokinins. The culture liquid exhibits cytokinin activity. The G + C content of
      DNA is 62.5 mol %, as determined from the DNA thermal denaturation temperature
      (Tm). Strain GB shows a moderate degree of DNA-DNA homology (< 40%) with the type
      representatives of the genus Paracoccus. Based on the data obtained, the
      bacterium was classified as a new species of this genus, named P. kondratievae.

PMID- 11315676
TI  - [Methylovorus mays--novel species of aerobic, obligatory methylotrophic bacteria
      associated with plants].
AB  - A bacterial strain utilizing methanol as the sole source of carbon and energy was
      isolated from the maize phyllosphere. Cells are nonpigmented gram-negative motile
      rods that do not form spores or prosthecae and reproduce by binary fission. The
      strain does not require vitamins or supplementary growth factors. It is
      obligately aerobic and urease-, oxidase-, and catalase-positive. The optimum
      growth temperature is 35-40 degrees C; the optimum pH is 7.0-7.5. The doubling
      time is 2 h. The bacterium implements the ribulose monophosphate pathway and
      possesses NAD(+)-dependent 6-phosphogluconate dehydrogenase and enzymes of the
      glutamate cycle. alpha-Ketoglutarate dehydrogenase and enzymes of the glyoxylate
      cycle (isocitrate lyase and malate synthase) are absent. Fatty acids are
      dominated by palmitic (C16:0) and palmitoleic (C16:1) acids. The major
      phospholipids are phosphatidylethanolamine, phosphatidylglycerol, and
      phosphatidylcholine. Cardiolipin is present in minor amounts. The dominant
      ubiquinone is Q8. The bacterial genome contains genes controlling the synthesis
      and secretion of cytokinins. The G + C content of DNA is 57.2 mol %, as
      determined from the DNA thermal denaturation temperature (Tm). The bacterium
      shows low DNA homology (< 10%) with restricted facultative methylotrophic
      bacteria of the genus Methylophilus (M. methylotrophus NCIMB 10515T and M.
      leisingerii VKM B-2013T) and with the obligate methylotrophic bacterium
      (Methylobacillus glycogenes ATCC 29475T). DNA homology with the type
      representative of the genus Methylovorus, M. glucosetrophus VKM B-1745T, is high
      (58%). The new isolate was classified as a new species, Methylovorus mays sp.
      now.

PMID- 11315677
TI  - [Evaluation of the effect of ecologically hazardous pollutants on the
      bacteriolytic activity of the predatory bacterium Bdellovibrio].
AB  - We studied the effect of various concentrations of ecologically hazardous
      pollutants, urea, phenol, diuron, and cadmium ions, on the physiological activity
      and survival of the parasitic bacterium Bdellovibrio. Experiments showed that the
      survival of bdellovibrios in the presence of the pollutants was two times higher
      when they were cultivated on agar than when they were cultivated in liquid
      medium. The data obtained are in agreement with the recent concept of the surface
      associated state as a survival strategy of bdellovibrios in various ecosystems.

PMID- 11315678
TI  - [Marine fungi in sediments of the Sea of Japan (Russian territory) and their
      biologically active metabolites].
AB  - The most abundant marine fungi encountered in various regions of the Sea of Japan
      belong to the genera Penicillium, Aspergillus, Wardomyces, Trichoderma,
      Chrysosporium, and Chaetomium. Facultative marine fungi of the genera
      Scytalidium, Verticillium, and Oidiodendron and obligate marine fungi of the
      genus Dendryphiella are much less abundant. The composition of marine sediments
      and the anthropogenic load on them were found to influence the abundance and
      species diversity of fungi, as well as the occurrence of fungal strains producing
      hemolytically active substances. The biodiversity of mycobiota and the abundance
      of hemotoxin-producing fungi in marine sediments may be used to evaluate the
      anthropogenic load on marine biocenoses. Hemolytic compounds were produced by 57%
      of the fungi isolated from marine sediments. The hemolytic activity of Chaetomium
      spiculipilium was revealed in the fraction of the culture liquid containing
      extracellular fatty acids and pigments. The fatty acid composition of this marine
      fungus was determined.

PMID- 11315679
TI  - [Regulation of the biomass and activity of soil microorganisms by microfauna].
AB  - Microcosm experiments showed that the microbial biomass and the respiration
      activity in soil were regulated by nematodes. Depending on nematode number and
      plant residue composition, the trophic activity of nematodes can either stimulate
      or inhibit microbial growth and respiration as compared to soil containing no
      nematodes. The stimulating effect was observed when nitrogen-free (starch) or low
      nitrogen (wheat straw, C:N = 87) organic substrates were applied. Inhibition
      occurred when a substrate rich in nitrogen (alfalfa meal, C:N = 28) was
      decomposed and the nematode population exceeded the naturally occurring level. A
      conceptual model was developed to describe trophic regulation by microfauna
      (nematodes) of the microbial productivity and respiration activity and
      decomposition of not readily decomposable organic matter in soil. The stimulating
      and inhibiting influence of microfauna on soil microorganisms was not a linear
      function of the rate of microbial consumption by nematodes. These effects are
      largely associated with the induced change in the physiological state of
      microorganisms rather than with the mobilization of biogenic elements from the
      decomposed microbial biomass.

PMID- 11315680
TI  - A combination of statistical methods for the analysis of the relative validation
      data of the quantitative food frequency questionnaire used in the THUSA study.
      Transition, Health and Urbanisation in South Africa.
AB  - OBJECTIVE: To apply structural equation modelling (SEM) and estimation of
      variance components to the relative validation data obtained from the
      quantitative food frequency questionnaire (QFFQ) used in the Transition, Health
      and Urbanisation in South Africa (THUSA) study. DESIGN: A cross-sectional study.
      SETTING: A community-based field study in an African population conducted during
      1996. SUBJECTS: Residents of the North West Province, South Africa, aged between
      15 and 65 years. METHODS: Relative validity of the QFFQ was tested against 7-day
      weighed food records, 24-hour urinary nitrogen (UN) excretion and estimated basal
      metabolic rate (BMR). SEM and estimation of variance components were applied to
      the log-transformed energy, protein, fat, calcium, iron, vitamin A and vitamin C
      intakes. UN excretion was used as a biomarker in the application of the SEM to
      protein and estimated BMR to energy intakes. RESULTS: Constant bias (alphaQ)
      derived by the SEM varied from 0.85 (vitamin C) to 5.8 (energy). There was
      significant proportional bias for all nutrients except vitamin C. Validation
      coefficients (ro(Q,T) varied from 0.3 (fat, calcium, iron) to 0.7 (vitamin C).
      The inclusion of estimated BMR in the SEM for energy increased ro(Q, T) from 0.38
      to 0.42. The estimation of variance components gave slightly lower correlations
      for the relationship between intakes from the QFFQ and the unknown true intake.
      CONCLUSIONS: Robust statistical methods were successfully applied in a relative
      validation study for a QFFQ in an African population. Estimated BMR as a
      biomarker for energy intake produced more meaningful results than UN excretion as
      a biomarker for protein intake.

PMID- 11315681
TI  - A culture-sensitive quantitative food frequency questionnaire used in an African
      population: 1. Development and reproducibility.
AB  - OBJECTIVE: To develop and assess the reproducibility of a quantitative food
      frequency questionnaire (QFFQ) sensitive to the culture of the African population
      of the North West Province, South Africa. DESIGN: A cross-sectional study.
      SETTING: A community-based field study in a population stratified according to
      level of urbanization from deep rural to urban upper class. SUBJECTS: A total of
      144 (99 women and 45 men) residents of the North West Province, aged between 15
      and 65 years. participated in the study. METHODS: A culture-sensitive. 145-item
      interviewer-administered QFFQ was designed to cover the whole diet. Portion sizes
      were estimated from a food portion photograph book (FPPB) showing foods in three
      portion sizes. The QFFQ was administered twice, 6-12 weeks apart. RESULTS:
      Spearman rank correlation coefficients between the two administrations varied
      from 0.14 for calcium to 0.75 for alcohol. The mean percentage difference between
      intakes was 8.5 (standard deviation= 9.9). Energy. protein, carbohydrate and
      calcium gave differences within 10%. Few significant differences among
      correlation coefficients or percentage difference for gender, age group or strata
      of urbanization were present. Bland-Altman plots showed significant proportional
      bias for protein, fibre and vitamin C. More than 70% of the participants were
      classified into adjacent quintiles for all nutrients. For food groups,
      correlation coefficients ranged from 0.25 for milk to 0.45 for vegetable and
      maize meal groups and 809/a of participants were classified into adjacent
      quintiles. CONCLUSIONS: The QFFQ appeared to be a reproducible dietary intake
      assessment instrument.

PMID- 11315682
TI  - A culture-sensitive quantitative food frequency questionnaire used in an African
      population: 2. Relative validation by 7-day weighted records and biomarkers.
AB  - OBJECTIVE: To determine the relative validity of the culture-sensitive
      quantitative food frequency questionnaire (QFFQ) developed for the Transition,
      Health and Urbanisation in South Africa (THUSA) study by 7-day weighed food
      records, urinary nitrogen excretion and basal metabolic rate (BMR). DESIGN: A
      cross-sectional study. SETTING: A community-based study in a population
      stratified according to level of urbanization. SUBJECTS: Residents of the North
      West Province, South Africa. aged between 15 and 65 years. The weighed food
      record study comprised 74 participants while 104 participants collected 24-hour
      urine samples. METHODS: All participants were interviewed using the QFFQ. For the
      weighed food record study, participants kept detailed weighed food diaries for
      seven consecutive days. For the urinary nitrogen study, participants made one 24
      hour urine collection. Completeness of the urine collections was checked against
      240 rug pan-aminobenzoic acid. BMR was estimated by the Schofield equations.
      RESULTS: Spearman rank correlation coefficients between the QFFQ and weighed food
      record ranged between 0.14 (fibre) and 0.59 (vitamin C). The QFFQ tended to
      underestimate intakes compared with the weighed records. Quintile distributions
      were similar for both methods. The correlation between urinary nitrogen excretion
      and dietary intake was poor. Possible underreporting was identified for 43% of
      the participants with the QFFQ and 28% with the weighed food record. CONCLUSIONS:
      The QFFQ appeared to be a relatively valid instrument for the assessment of
      dietary intakes of the population of the North West Province. The use of
      biomarkers in this population was difficult and needs further investigation.

PMID- 11315683
TI  - A brief dietary assessment instrument for assessing target foods, nutrients and
      eating patterns.
AB  - OBJECTIVE: To develop and validate a new dietary assessment tool, the focused
      recall, and to use this to measure co-consumption of carotenoid-containing fruits
      and vegetables with savory snacks. DESIGN: Participants completed a telephone
      administered focused recall and a 24-hour recall on the same day. We compared
      mean estimates of fruit, vegetable, savory snack and carotenoid consumption from
      both instruments. We also assessed the ability of each method to measure co
      consumption of carotenoids with full-fat, reduced/non-fat and olestra-containing
      savory snacks. SETTING AND SUBJECTS: Data are from 245 male and 244 female adult
      participants in the Olestra Post-Marketing Surveillance Study (OPMSS). RESULTS:
      The mean (=/- SD) intake of fruit was 1.8(1.1) servings day(-1) from the focused
      recall and 1.6 (1.4) servings day(-1) from the 24-hour recall (r=0.56). The mean
      vegetable intake was 2.1 (1.3) and 2.2 (1.7) servings day(-1) (r=0.42),
      respectively, from each instrument. Estimates of total carotenoid and beta
      carotene intake were within 5% of each other (r= 0.63 for total carotenoids and
      r= 0.70 for beta-carotene). Both instruments estimated that approximately 14% of
      total daily carotenoids were co-consumed with savory snacks (r= 0.63).
      CONCLUSIONS: The focused recall provides valid information about fruit, vegetable
      and savory snack consumption and allows researchers to examine associated eating
      patterns more easily.

PMID- 11315684
TI  - Psychoanalytic perspectives on the religious experience.
AB  - This paper carries out an analysis of the nature of mature religiosity of the
      basis of psychoanalytic findings and concepts, rather than attempting a
      philosophical and theological approach to religion. It highlights a striking
      correspondence between the characteristics of mature religiosity, derived from
      the various sources of development of the ego-ideal and the superego, and
      reflecting a dominance of love over hatred, of libido over the death drive as an
      aspect of psychological health and maturity, on the one hand, and the
      characteristics of the Deity in Judeo-Christian religions, on the other. At a
      clinical level, one of the functions of the psychotherapist is to explore the
      extent to which religiosity as a mature desire for a transpersonal system of
      morality and ethical values is available to our patients. Psychotherapy also has
      to help certain patients to free themselves from the use of formal religious
      commitments as a rationalization of hatred and destructiveness directed against
      self or others.

PMID- 11315685
TI  - Effects of massage on pain intensity, analgesics and quality of life in patients
      with cancer pain: a pilot study of a randomized clinical trial conducted within
      hospice care delivery.

PMID- 11315686
TI  - Public health implications of licensing law.

PMID- 11315687
TI  - Trends in hospital admissions for fractures of the hip and femur in England, 1989
      1990 to 1997-1998.
AB  - BACKGROUND: Fractures of the hip are a major public health issue. Suggestions of
      a recent stabilization of age-specific admission rates would have implications
      for health service planning, thus we investigated this using hospital data.
      METHOD: Hospital episode statistics for England, 1989-1990 to 1997-1998, were
      examined for admissions and deaths for fractures of the hip and femur in NHS
      hospitals in patients aged 45 years and over. RESULTS: Age-standardized admission
      rates increased by 32 per cent between 1989-1990 and 1997-1998 in men, and by 30
      per cent in women. The increase in admission rates was almost entirely confined
      to the period 1989-1990 to 1991-1992, with very little change after this. The
      proportion of admissions ending in death during the study period decreased in
      both men (-35 per cent) and women (-40 per cent) but this change was largely
      confined to the early years of the study. The number of admissions from hip and
      femoral fractures in people aged 65 years and over is projected to increase from
      about 57,300 in 1997-1998 to 69,500 by 2021-2022. CONCLUSIONS: Age-specific rates
      of admission appear to be stabilizing, which is in contrast to previous trends.
      The lack of any decrease in hospital admission and mortality rates over the last
      5 years is of concern. The management of osteoporosis-induced fractures in
      hospitals, the prevention and treatment of osteoporosis in primary care and the
      prevention of falls should be seen as priorities for the NHS to help reduce the
      burden of disease from osteoporosis in the elderly.

PMID- 11315688
TI  - Mercury contamination incident.
AB  - BACKGROUND: The aim of this paper is to describe an incident where elemental
      mercury led to widespread contamination and the exposure of 225 individuals and
      confirmed toxicity in 19 individuals. The paper describes the incident and
      difficulties found in trying to assess the risk to individuals and to identify
      and decontaminate the residences involved. METHODS: All individuals exposed to
      elemental mercury in the incident were followed up for 15 months. RESULTS: Thirty
      seven individuals were found to be 'at risk' and 13 were symptomatic of mercury
      poisoning. Five patients required chelation therapy. The incident was closed when
      the risk of poisoning and re-exposure was minimized. CONCLUSION: Incident
      management depends on early effective communication and collaboration between all
      agencies involved.

PMID- 11315689
TI  - Does poor communication contribute to stillbirths and infant deaths? A review.
AB  - BACKGROUND: Assessors from the Confidential Enquiry into Stillbirths and Deaths
      in Infancy (CESDI) have cited poor communication as a contributory factor in a
      proportion of such deaths. This review assesses what research evidence exists to
      support or explain this. METHODS: A structured review was carried out, including
      all studies of sub-optimal care in stillbirth or infant death and studies of
      litigation in perinatal care. The following databases were searched: MEDLINE,
      PsycLIT, The Cochrane Library, BIDS Science and Social Science Citation Indexes,
      Cinahl and Embase. For included studies, information was extracted on the type of
      study, the selection criteria and number of cases studied, other methods used and
      results relevant to the question. RESULTS: One hundred and four studies of
      potential relevance to the review were identified. Of these, 52 did not meet the
      inclusion criteria and were excluded. Of the remaining 52 studies, 11 considered
      communication failure explicitly as a factor in sub-optimal care leading to
      stillbirth or infant death. In three out of the four studies that presented their
      findings in terms of numbers of cases, communication failure was noted in between
      24 and 29 per cent of cases. There was some consistency across different types of
      study in the types of communication problems noted. CONCLUSION: Poor
      communication may contribute to a proportion of stillbirths and infant deaths.
      However, given the small number of papers that looked explicitly at poor
      communication as a factor in sub-optimal care and the lack of comparative
      information on communication in cases that do not end in poor outcome, caution is
      needed in drawing conclusions based on the findings of these papers.

PMID- 11315690
TI  - Steering a course around the genetic iceberg.
AB  - A US company is now marketing worldwide, via the Internet, genetic testing for
      predisposition to breast and ovarian cancer. This paper explores some of the
      divergent concerns about the implications of private genetic testing for the
      United States and United Kingdom, with their differing health care systems. As
      the UK National Health Service faces calls for expansion in its genetic services
      to meet growing demand, there is now a need for evaluation of the costs and
      effectiveness of such services so that they may be efficiently targeted to those
      women who can benefit most from them. In the cases of breast and ovarian cancer,
      it is relatively straightforward to calculate the benefits in terms of added life
      expectancy and health-related quality of life resulting from earlier diagnosis
      and treatment of affected women, but these women are likely to be a small
      proportion of the total number of women who are referred or self-refer to genetic
      services. This paper asks how we are to measure and value the benefits of
      information about risk of cancer to a particular woman or to members of her
      family; how we are to measure and value the benefits of effective counselling,
      which encourages autonomous, informed decision-making about whether or not to
      undergo genetic testing, and which facilitates comprehension of complex results;
      and ultimately, in the face of advances in genetic science, how we are to steer
      the NHS around the genetic iceberg.

PMID- 11315691
TI  - Equal opportunities, equal risks? Overuse injuries in female military recruits.
AB  - BACKGROUND: The rate of female personnel medically discharged from service in the
      British Army has been rising steadily since 1992 from around 3 per 1,000 per year
      to over 35 per 1,000 in 1996, although there has been only a minor increase in
      medical discharges for males over the same period. This paper examines the
      increasing rate of medical discharge in young female members of the British Army
      from an aetiological perspective and reviews the literature to identify risk
      factors that may be relevant. METHODS: Data from published military medical
      statistical reports were reviewed and the clinical records of a 10 per cent
      sample of females medically discharged for relevant conditions were examined.
      RESULTS: The majority of the excess medical discharges had occurred in females
      under the age of 22 and were due to musculoskeletal disorders and injuries caused
      by military training. Data from the clinical records showed that 75.5 per cent
      (37/49) of those medically discharged for these conditions were recruits. Stress
      fractures and other overuse syndromes accounted for 70.2 per cent of medical
      discharges among the recruits in the sample. CONCLUSION: Females undertaking
      strenuous exercise alongside males are at increased risk of injury. Risk factors
      include smoking, short stature, restricted dietary intake and menstrual
      disturbance. Equal opportunities legislation has been interpreted to require
      identical training for males and females, but some segregation of training may be
      acceptable provided the outcome of training is no less favourable to either
      gender, and this may reduce the excess risk of injury to females.

PMID- 11315692
TI  - Why do we continue to use standardized mortality ratios for small area
      comparisons?
AB  - Public health practitioners are often faced with the necessity to compare the
      mortality experience of different geographical areas. Indirect standardization,
      producing a 'standardized mortality ratio' (SMR) is the most commonly used
      technique for doing this. However, as we show, indirect standardization is
      inappropriate for such comparisons, as SMRs for different geographical areas have
      different denominators. The fact that indirect standardization is usually chosen
      for this type of comparison is probably based on two beliefs: (1) that direct
      standardization yields only a rate rather than a more easily interpreted ratio or
      index; (2) that direct standardization cannot be carried out in many cases
      because the sub-group specific mortality rates in the groups to be compared are
      not available or, in at least some age classes, are based upon such small numbers
      as to be completely unreliable. In this paper we show that a simple index (the
      comparative mortality figure) can be calculated from the directly standardized
      rate in most cases. Using a comparison of the overall mortality experience of
      electoral wards in Sheffield between 1980 and 1987 we demonstrate also that the
      advantage gained by the smaller standard error of the SMR is outweighed by the
      bias inherent in its construction. We recommend that the SMR is used only when
      absolutely necessary, that is, in the rare circumstance when data are not
      available for the calculation of age- and sex-specific subgroup rates in the
      study population.

PMID- 11315693
TI  - The efficiency of the delivery of neonatal care in the UK.
AB  - BACKGROUND: A recent paper in Journal of Public Health Medicine (O'Neill et al.,
      2000; 22(1): 108-115) used regression modelling to determine the average costs of
      neonatal care services for a sample of 49 units in the United Kingdom in 1990
      1991, and concluded that economies of scale were present in the sample as a
      whole. Although this form of modelling is useful, analysis of the efficiency of
      production for individual units is also important. METHODS: Data envelopment
      analysis (DEA) was used to analyse the data set published by O'Neil et al., to
      determine technical efficiency of neonatal units, measuring efficiency compared
      with a benchmark efficient frontier, and estimating economies of scale for each
      unit. Potential cost savings if units were to operate efficiently are estimated.
      RESULTS: There is evidence of substantial levels of technical inefficiency.
      Economies of scale varied between units, with increasing returns in the 36
      inefficient units, and mainly constant returns in the 13 efficient units. This
      suggests that the presence of technical inefficiency was as important as scale
      inefficiencies. Total cost savings, if all units were operating efficiently, are
      estimated at l10.4 million, equivalent to 10 extra units producing 57,000
      additional days of care. CONCLUSIONS: DEA is a technique of great potential value
      in analysing the efficiency of health care production. As well as inefficiencies
      in the production of neonatal care in the United Kingdom due to differences in
      the scale of production, there appears to have been considerable technical
      inefficiency, which was not due to differences in case mix. The potential cost
      savings from efficiency gains are large.

PMID- 11315694
TI  - Joint working, reality or rhetoric?
AB  - The UK Government has put the elimination of health inequalities and social
      exclusion at the heart of its agenda. Partnership working is clearly needed to
      tackle these issues and has been identified as the way forward in a series of
      policy initiatives. This paper explores whether, despite the rhetoric, joint
      working happens in reality. Using the example of the Social Exclusion Unit, a
      'cross-cutting' unit developed to work across organizational boundaries, it
      suggests that centrally joint working is not working effectively. As a result,
      public health programmes are not being well co-ordinated with wider government
      initiatives and public health appears to be excluded from much of the work around
      social exclusion. Two potential reasons are identified: (1) poor co-ordination
      between the Department of Health and the Cabinet Office; (2) a lack of
      understanding in the wider community of public health and the role it can play in
      tackling inequalities and social exclusion. A House of Commons Health Committee
      is currently examining co-ordination between central government, local government
      and health authorities in delivering public health. Meanwhile, the public health
      community must attempt to clarify and, if necessary, market its role and
      strengths in this sphere. Unless directives from central government are better co
      ordinated, local efforts to work in partnership could be undermined.

PMID- 11315695
TI  - Accessing and using hospital activity data.
AB  - Hospital activity data can be accessed from a variety of sources ranging from
      hospitals to the Department of Health. These data provide valuable and widely
      used information, but care is needed in their use and interpretation. Hospital
      activity rates reflect not only the underlying prevalence and severity of
      disease, individual factors and referral practices, but also variations related
      to provider-specific factors: the 'provider effect'. This includes completeness
      in the data, supply of hospital beds, admission policies, hospital access and
      distance from hospital. The provider effect can be controlled to a certain extent
      in statistical analyses. Although data quality has improved considerably in the
      last decade, this should still be investigated where trusts are being compared
      and in small area studies because missing data may lead to artefactual
      differences in rates. 'Dump' postcodes, where missing or unknown postcodes are
      assigned to a local postcode such as that of the hospital, may affect small area
      analyses and linkage if a proxy patient identifier is constructed that includes
      postcode.

PMID- 11315696
TI  - The first year of Health Improvement Programmes; views from Directors of Public
      Health.
AB  - BACKGROUND: The White Paper The new NHS, modern, dependable gave the strategic
      lead at the local level in the new National Health Service to Health Authorities
      (Boards in Scotland and Northern Ireland). They are expected to lead the
      development of strategies that will identify the health needs of local people and
      what has to be done to meet them. These Health Improvement Programmes (HImPs)
      will be the local strategy for improving health and health care and the means to
      achieve national targets for each Health Authority or Board area. METHOD: To
      assess the strengths and weaknesses of HImP production for 1999, a questionnaire
      survey was carried out of Health Authorities or Boards throughout the United
      Kingdom. Participants were all district Directors of Public Health (DsPH) or
      Chief Administrative Medical Officers (CAMOs). The main outcome measures were the
      opinions of DsPH or CAMOs on the successes and failures of their local HlmP
      process. RESULTS: Ninety-three (83.8 per cent) DsPH responded. In just over half
      of all Health Authorities or Boards (56 per cent) the DsPH had taken the lead in
      producing the HlmP. Many aspects of the HlmP process went well, including
      multiagency 'stakeholder' involvement and partnership working, good project
      management, and agreeing a limited set of priorities for action. Key problems
      included: the short timescale and late Departments of Health guidance; difficulty
      in obtaining commitment from some local 'stakeholders'; linking HlmP aspirations
      with service and financial planning and securing funding for HlmP priority
      developments. Action plans to improve health and health care services were well
      developed in 40.5 per cent of HlmPs. This was less so for social services (8.3
      per cent). It was too soon to assess the impact of HlmPs on the public's health.
      CONCLUSIONS: DsPH or CAMOs and local 'stakeholders' have been on a learning curve
      for HlmP production during 1999. Lessons learnt will translate into better HlmPs
      for next year. DsPH urged the Departments of Health to fully support HlmPs
      through resources and management processes so that HlmPs can realize their
      potential benefits for local populations.

PMID- 11315697
TI  - If the NHS introduced a '50 procedures a year' policy, what proportion of
      consultant firms would be affected?
AB  - BACKGROUND: Governments, insurers, quality assurance agencies and others have
      used the higher volume = better quality relationship as a basis for health
      policy. This relationship is probably real enough to justify these policies.
      However, even if it were not real, there are other reasons why these and other
      organizations such as the National Health Service (NHS) may favour high-volume
      providers. This paper attempts to answer the question: 'If, for common elective
      procedures, the NHS instituted a high-volume purchasing policy that requires
      consultant firms to perform a minimum of "50 procedures a year", what proportion
      of consultant firms would be affected?' The aims of this study were to estimate
      the proportion of NHS consultant firms that perform common elective procedures
      less than 50 times a year and to estimate the proportion of firms that would have
      to stop providing these procedures if a '50 procedures a year' purchasing policy
      were introduced. METHOD: A descriptive analysis was carried out and modelling was
      performed on data stored in an NHS health episode statistics database of patients
      treated in West Midlands NHS facilities. For each of 12 common elective
      procedures we assumed that a volume threshold of at least 50 a year were set, and
      calculated the proportion of NHS consultant firms undertaking each procedure who
      performed less than 50 of those procedures each year and the proportion of firms
      who would have had to stop providing each procedure. RESULTS: All firms
      performing some procedures, e.g. cataract extraction, did so at least 50 times a
      year. By contrast, no firm repaired more than 50 recurrent inguinal hernias a
      year. If a volume threshold of at least 50 procedures a year were set for a
      basket of 12 common elective procedures, then about 40 per cent of firms would no
      longer be eligible to provide a procedure. Even if a lower 'one a month'
      threshold were set, about 20 per cent of firms would still not be eligible to
      provide that procedure. CONCLUSION: Introduction of a high-volume policy would
      affect a considerable number of firms, as many NHS consultant firms perform some
      common elective procedures infrequently. Some consultants would see the
      introduction of a high-volume policy as an opportunity to further specialize and
      super-specialize. Others would see it as a policy that restricts them to
      providing a narrower range of procedures, makes their professional practice less
      interesting, and reduces their professional autonomy. Postgraduate training
      institutions need to consider the possibility and implications of high-volume
      policies, as many junior doctors would probably need to learn to provide a
      narrower range of skills than at present.

PMID- 11315698
TI  - Trends in antibiotic prescribing and associated indications in primary care from
      1993 to 1997.
AB  - BACKGROUND: Recent concerns that evidence on the appropriate use of antibiotics
      is not having an impact on prescribing trends are based on UK prescribing data
      relating to 1980-1991. The aim of this paper is to determine trends in antibiotic
      prescribing from 1993 to 1997 and link antibiotic prescriptions to diagnostic
      categories. METHODS: A retrospective analysis of antibiotic prescriptions linked
      to diagnostic codes was carried out using the West Midlands General Practice
      Research Database. RESULTS: The prescribing rate for antibiotics fell from 963
      prescriptions/1,000 patients in 1993 to 807 prescriptions/1,000 patients in 1997
      (p < 0.001). The proportion of antibiotic prescribing for respiratory conditions
      fell from 65 per cent in 1993 to 59 per cent in 1997 (p < 0.001). The main
      decreases in antibiotic prescribing are accounted for by non-specific lower
      respiratory tract infections (-22 prescriptions/1,000 patients), non-specific
      upper respiratory tract infections (-21/1,000 patients) and throat infections (
      20/1,000 patients). There was increased prescribing for non-respiratory
      miscellaneous conditions (+6 prescriptions/1,000 patients). CONCLUSIONS: Overall
      antibiotic prescribing declined by 16 per cent between 1993 and 1997, primarily
      for respiratory conditions. These results of the current study are in marked
      contrast to an earlier review, which found an increase of 46 per cent between
      1980 and 1991 in England. The level of antibiotic prescribing for conditions
      which may not be bacterial in origin is still high and there is scope for further
      reductions in antibiotic prescribing. This study highlights the need for regular
      epidemiological data to inform the debate on antibiotic prescribing.

PMID- 11315699
TI  - Increasing National Health Service funding: implications for welfare and justice.
AB  - Two of the fundamental purposes for establishing the National Health Service
      (NHS) were to increase social welfare and improve social justice. Decisions to
      increase NHS investment should ideally be taken with these fundamental objectives
      in mind. Given that society faces resource constraints, increased financial
      investment in the NHS will always involve forgone investment elsewhere, and it
      may never be possible to determine with any degree of certainty whether further
      real investment in the NHS will increase overall social welfare. If the
      Government decides to increase NHS investment for political reasons, it should
      therefore at least try to ensure that the methods by which it raises extra
      revenue improve social justice. The introduction of an NHS premium payment for
      high earners would be a progressive measure consistent with this objective.

PMID- 11315700
TI  - Variation in mortality rates in Australia: correlation with Indigenous status,
      remoteness and socio-economic deprivation.
AB  - BACKGROUND: The aim of this study was to study ecological correlations between
      age-adjusted all-cause mortality rates in Australian statistical divisions and
      (1) the proportion of residents that self-identify as Indigenous, (2) remoteness,
      and (3) socio-economic deprivation. METHODS: All-cause mortality rates for 57
      statistical divisions were calculated and directly standardized to the 1997
      Australian population in 5-year age groups using Australian Bureau of Statistics
      (ABS) data. The proportion of residents who self-identified as Indigenous was
      obtained from the 1996 Census. Remoteness was measured using ARIA (Accessibility
      and Remoteness Index for Australia) values. Socioeconomic deprivation was
      measured using SEIFA (Socio-Economic Index for Australia) values from the ABS.
      RESULTS: Age-standardized all-cause mortality varies two-fold from 5.7 to 11.3
      per 1,000 across Australian statistical divisions. Strongest correlation was
      between Indigenous status and mortality (r = 0.69, p < 0.001). Correlation
      between remoteness and mortality was modest (r = 0.39, p = 0.002) as was
      correlation between socio-economic deprivation and mortality (r = -0.42, p =
      0.001). Excluding the three divisions with the highest mortality, a multiple
      regression model using the logarithm of the adjusted mortality rate as the
      dependent variable showed that the partial correlation (and hence proportion of
      the variance explained) for Indigenous status was 0.03 (9 per cent; p = 0.03),
      for SEIFA score was -0.17 (3 per cent; p = 0.22); and for remoteness was -0.22 (5
      per cent; p = 0.13). Collectively, the three variables studied explain 13 per
      cent of the variability in mortality. CONCLUSIONS: Ecological correlation exists
      between all-cause mortality, Indigenous status, remoteness and disadvantage
      across Australia. The strongest correlation is with Indigenous status, and
      correlation with all three characteristics is weak when the three statistical
      divisions with the highest mortality rates are excluded. Intervention targeted at
      these three statistical divisions could reduce much of the variability in
      mortality in Australia.

PMID- 11315701
TI  - Quarterly Communicable Disease Review July to September 2000--from the PHLS
      Communicable Disease Surveillance Centre.

PMID- 11315702
TI  - Tuberculosis screening of new entrants; how can it be made more effective?

PMID- 11315703
TI  - The virtuous public health physician.

PMID- 11315704
TI  - Excess winter deaths.

PMID- 11315705
TI  - Primary care trust--threat or opportunity to public health medicine.

PMID- 11315706
TI  - Searching for decision thresholds to predict outcome using ovarian diameter and
      follicle numbers.

PMID- 11315707
TI  - Selection of controls--always a challenge.

PMID- 11315708
TI  - Revisiting lessons from the C57BL/6J mouse.

PMID- 11315709
TI  - Strategies to reduce deaths from breast cancer following mantle irradiation.

PMID- 11315710
TI  - Risk-adapted therapy for clinical stage I-II Hodgkin's disease: 7-years results
      of radiotherapy alone for low-risk disease, and ABVD and radiotherapy for high
      risk disease.
AB  - Treatment outcomes were documented for 204 adult patients with clinical Stage I
      II Hodgkin's disease who were treated with risk-adapted ABVD (doxorubicin,
      bleomycin, vinblastine and dacarbazine) and radiotherapy (RT) at the Toronto
      Sunnybrook Regional Cancer Centre between 1984 and 1994. Forty-nine patients with
      clinical Stage I disease (excluding bulky mediastinal presentations) and 50
      patients with a combination of clinical Stage IIA disease, age 50 years or less,
      and favourable pathology (lymphocyte predominant or nodular sclerosing histology)
      were identified as low risk and treated with RT alone to 35 Gy. One hundred and
      five high-risk patients were treated with chemotherapy (86 with ABVD) followed by
      RT to 25 Gy. The 7-year cause-specific, overall and disease-free survivals were
      95%, 90% and 75% respectively for the low-risk cohort, and 91%, 90% and 88%
      respectively for the high-risk cohort. In-field relapses accounted for 50% of the
      failures in both groups. Sixteen of 24 (67%) patients with RT failure and 6/14
      (43%) with combined modality therapy (CMT) failure were salvaged. Twenty-eight
      per cent of the patients treated with RT and 21% of those treated with CMT
      developed hypothyroidism by 7 years. Fatal complications were recorded in 6% of
      the low-risk patients managed with RT and 8% of high-risk patients managed with
      CMT. Septic death and second malignancy accounted for the majority of treatment
      related fatalities. Risk-adapted therapy emphasizing RT alone for selected
      patients with favourable prognostic factors and CMT based on ABVD provides
      excellent long-term disease control. Further treatment refinements, including the
      wider application of CMT with lower doses of chemotherapy and RT, will be
      required to reduce the rate of fatal complications to more acceptable levels.

PMID- 11315711
TI  - Early onset of bilateral brachial plexopathy during mantle radiotherapy for
      Hodgkin's disease.
AB  - We report a case of brachial plexus neuropathy occurring in a 50-year-old man
      treated with standard mantle radiotherapy for early-stage Hodgkin's disease. A
      dose of 35 Gy in 20 fractions was given to the mantle field, following by a boost
      to the right side of the neck (8 Gy in four fractions). The onset of symptoms was
      early in the course of treatment and a gradual and almost full recovery was
      observed over 3 years after completion ofradiotherapy. The diagnosis was
      supported by electromyography. The temporal relationship of the radiotherapy and
      the onset of the brachial plexus neuropathy suggests a cause and effect, but this
      association is rarely reported after mantle radiotherapy. We review the aetiology
      of this condition and postulate possible mechanisms in this patient.

PMID- 11315712
TI  - Hypopyon uveitis and iris nodules in non-Hodgkin's lymphoma: ocular relapse
      during systemic remission.
AB  - We report the case history of a patient with peripheral non-Hodgkin's lymphoma in
      systemic remission, who presented with a pseudohypopyon and iris nodules. Iris
      biopsy confirmed the presence of intraocular tumour, which subsequently responded
      to orbital radiation. Ocular remission, however, was soon followed by a systemic
      relapse, suggesting that the eye may act as a sanctuary site for tumour cells
      during chemotherapy, and that cells may metastasize from the eye back to the
      periphery during systemic remission.

PMID- 11315713
TI  - Nasal natural killer-cell lymphoma: a disease with very poor prognosis.
AB  - Nasal Natural Killer-Cell Lymphoma is an aggressive subtype of NHL even when it
      presents with localized disease. It is more common in Oriental than Western
      population. We report the case history of a white Caucasian male patient with
      this disease who died 5 months from diagnosis despite aggressive treatment with 2
      different chemotherapy regimes and radiotherapy. We discuss the diagnosis,
      presentation, treatment and prognosis of this rare disease.

PMID- 11315714
TI  - Familial breast cancer: the problems of circumstantial evidence.

PMID- 11315715
TI  - A patient with 17 primary tumours and a germ line mutation in TP53: tumour
      induction by adjuvant therapy?
AB  - We report the case history of a woman with a germ line mutation in the TP53 gene
      who developed 17 separate primary tumours. The incidence of new tumours rose
      steeply after adjuvant tamoxifen treatment for breast cancer and adjuvant vaginal
      vault radiotherapy for endometrial cancer. This increase could be due to
      cumulative genetic damage from environmental agents and the fact that the patient
      lived to the relatively late age of 60 years, or to a high inherent deleterious
      somatic mutation rate, which could represent the inability of cells from patients
      with TP53 mutations to repair therapy-induced genetic damage.

PMID- 11315716
TI  - Simultaneous breast cancer in non-identical Ashkenazi Jewish twins: management
      dilemmas when genetic testing is negative.
AB  - We present the case histories of Ashkenazi Jewish twins of opposite sex who
      developed breast cancer simultaneously, in whom testing for the anticipated BRCA2
      mutations was unexpectedly negative. Their management and the implications of
      this difficult situation are discussed.

PMID- 11315717
TI  - Axillary recurrence following conservative surgery and radiotherapy in early
      breast cancer.
AB  - At the institute, since the late 1980s, there has been a uniform treatment
      protocol for the management of the regional lymph nodes in patients referred for
      radiotherapy following breast-conserving surgery. An analysis of 2,277
      consecutive patients referred for radiotherapy between 1989 and 1992, with
      particular reference to regional lymph node management, has been undertaken.
      Axillary surgery alone was used in 517 patients (23%); 1,191 (52%) patients had
      no axillary surgery but had radiotherapy to the axilla, and infraclavicular and
      supraclavicular fossae by a single anterior field, delivering 40 Gy in 15 daily
      fractions over 3 weeks; and 474 patients (21%) had axillary surgery followed by
      radiotherapy. Ninety-five patients (4%) underwent no axillary treatment. There
      was a total of 155 axillary recurrences with a median follow-up of 5.9 years,
      giving an actuarial nodal control rate of 94% at 5 years (95% confidence interval
      (CI) 93.1-95.1). The overall survival at 5 years was 86% (95% CI 84.6-87.5).
      There was a trend towards improved axillary control with surgery alone compared
      with radiotherapy alone (4.5% versus 5.9% actuarial axillary failure rate at 5
      years). An extremely low incidence of brachial plexus neuropathy secondary to
      radiotherapy was reported. The multidisciplinary treatment protocol used gave a
      high rate of regional node control, with minimal recorded morbidity.

PMID- 11315719
TI  - Prophylactic cranial irradiation in small cell lung cancer: who gets it?

PMID- 11315718
TI  - Variations in dose and dose intensity of adjuvant CMF chemotherapy for breast
      cancer throughout the UK.
AB  - Cyclophosphamide, methotrexate and 5-fluorouracil (CMF) is a commonly prescribed
      regimen for the adjuvant treatment of early breast cancer in the UK and in other
      countries with a high incidence of breast carcinoma. A number of variations in
      dose and scheduling of these drugs have been reported in the literature, with all
      of these being recognized under the generic term 'CMF'. To investigate the extent
      of differences in CMF regimens used for the adjuvant treatment of early breast
      cancer we sent a postal questionnaire to all consultant medical and clinical
      oncologists in the UK seeking details of their practice. CMF drug doses were then
      converted into dose intensity parameters for comparison. The results showed a
      wide variation in the number of CMF schedules (n = 36) and CMF dose intensities
      (n = 33) used. The potential consequences of such variation and the evidence for
      and against dose intensity as an important parameter in the adjuvant treatment of
      early breast cancer are discussed.

PMID- 11315720
TI  - Small cell lung cancer as a cause of acute renal failure secondary to bilateral
      renal infiltration.
AB  - We describe a patient with acute renal failure resulting from bilateral
      infiltration of the kidneys by metastases secondary to small cell lung cancer.
      Treatment with chemotherapy led to a response regarding tumour size and
      normalization of renal function. We are not aware of this being described
      previously.

PMID- 11315721
TI  - Radiation myelitis and thoracic radiotherapy: evidence and anecdote.

PMID- 11315722
TI  - A short course of palliative radiotherapy for inoperable non-small cell lung
      cancer: biologically effective dose on spinal cord.

PMID- 11315723
TI  - Spontaneous regression of carcinoma of the stomach.

PMID- 11315724
TI  - Post-irradiation erythroderma.

PMID- 11315725
TI  - Bullous skin disorders following radiotherapy.

PMID- 11315726
TI  - Computerizing the cancer centre: the mathematics of survival.

PMID- 11315727
TI  - Guidelines on the management of adult testicular cancer.

PMID- 11315728
TI  - Psychometric evaluation of the Beck Depression Inventory-II with primary care
      medical patients.
AB  - This study evaluated the psychometric characteristics of the Beck Depression
      Inventory-II (BDI-II; A. T. Beck, R. A. Steer, & G. K. Brown, 1996) in a primary
      care medical setting. A principal-components analysis with Promax rotation
      indicated the presence of 2 correlated factors, Somatic-Affective and Cognitive,
      which explained 53.5% of the variance. A hierarchical, second-order analysis
      indicated that all items tap into a second-order construct of depression.
      Evidence for convergent validity was provided by predicted relationships with
      subscales from the Short-Form General Health Survey (SF-20; A. L. Stewart, R. D.
      Hayes, & J. E. Ware, 1988). A receiver operating characteristic analysis
      demonstrated criterion-related validity: BDI-II scores predicted a diagnosis of
      major depressive disorder (MDD), as determined by the Primary Care Evaluation of
      Mental Disorders (PRIME-MD) Patient Health Questionnaire (PHQ). This study
      demonstrated that the BDI-II yields reliable, internally consistent, and valid
      scores in a primary care medical setting, suggesting that use of the BDI-II in
      this setting may improve detection and treatment of depression in these medical
      patients.

PMID- 11315729
TI  - The role of behavioral experience in judging risks.
AB  - This study used conditional risk assessments to examine the role of behavioral
      experiences in risk judgments. Adolescents and young adults (ages 10-30; N = 577)
      were surveyed on their risk judgments for natural hazards and behavior-linked
      risks, including their personal experiences with these events. Results indicated
      that participants who had experienced a natural disaster or engaged in a
      particular risk behavior estimated their chance of experiencing a negative
      outcome resulting from that event or behavior as less likely than individuals
      without such experience. These findings challenge the notion that risk judgments
      motivate behavior and instead suggest that risk judgments may be reflective of
      behavioral experiences. The results have implications for health education and
      risk communication.

PMID- 11315730
TI  - Identifying trajectories of adolescent smoking: an application of latent growth
      mixture modeling.
AB  - The goal of the current study was to identify discrete longitudinal patterns of
      change in adolescent smoking using latent growth mixture modeling. Five distinct
      longitudinal patterns were identified. A group of early rapid escalators was
      characterized by early escalation (at age 13) that rapidly increased to heavy
      smoking. A pattern characterized by occasional puffing up until age 15, at which
      time smoking escalated to moderate levels was also identified (late moderate
      escalators). Another group included adolescents who, after age 15, began to
      escalate slowly in their smoking to light (0.5 cigarettes per month) levels (late
      slow escalators). Finally, a group of stable light smokers (those who smoked 1-2
      cigarettes per month) and a group of stable puffers (those who smoked only a few
      puffs per month) were also identified. The stable puffer group was the largest
      group and represented 25% of smokers.

PMID- 11315731
TI  - Accuracy of health-related quality of life assessment: what is the benefit of
      incorporating patients' preferences for domain functioning?
AB  - This study investigated the accuracy benefit of incorporating patients'
      preferences for domains of functioning into health-related quality of life
      (HRQOL) measurement. Using policy-capturing techniques, 102 medical outpatients
      judged the HRQOL of 16 scenarios describing varying levels of functioning in 3
      domains. For each participant, regression analysis determined relative domain
      preferences and 2 decision models were built: one incorporating (preference
      weighted) and one ignoring (equally weighted) domain preferences. To assess
      accuracy, the average proportion of judgment variance accounted for by each model
      was determined and both accounted for approximately 50%. However, for patients
      showing the greatest differences in importance across domains, the preference
      weighted model was more accurate. Findings are discussed in the context of
      enhancing HRQOL assessment.

PMID- 11315732
TI  - Psychological factors and depressive symptoms in ischemic heart disease.
AB  - The aim of this study was to determine whether learned helplessness, cognitive
      distortions, self-efficacy, and dispositional optimism assessed at Time 1 (T1;
      questionnaires mailed at 1 month postdischarge) would predict depressive symptoms
      at Time 2 (T2; questionnaires mailed at 1-year follow-up) in a sample of 86
      patients hospitalized with ischemic heart disease. Multiple regression results
      indicated that optimism and cognitive distortions at T1 were significantly
      associated with T1 depressive symptoms after controlling for confounding
      variables. When the T1 psychological factors were analyzed with T2 depressive
      symptoms, only optimism continued to predict depressive symptoms after
      controlling for confounds and T1 depressive symptoms. The global expectancies
      that optimism assessed appeared to be more stable over time than the statelike
      beliefs of cognitive distortions and may have accounted for why optimism
      predicted T2 depressive symptoms.

PMID- 11315733
TI  - Explaining retrospective reports of symptoms in patients undergoing chemotherapy:
      anxiety, initial symptom experience, and posttreatment symptoms.
AB  - This study evaluated different perspectives on the relationship of trait anxiety
      to symptom report. Baseline trait anxiety was related to (a) initial symptoms
      reported 2 days after beginning chemotherapy, (b) posttreatment symptoms reported
      2 days after cessation of medication, and (c) retrospective reports of initial
      symptoms (made concurrently with posttreatment reports). Associations were
      significant for vague psychophysiological symptoms but not for concrete visible
      symptoms. Path models indicated that the relationship of anxiety to retrospective
      report of vague symptoms was due to both enhanced encoding and facilitated recall
      of symptoms. Further analyses revealed, however, that this relationship reflects
      symptoms stability rather than anxiety-related differences in attention. Anxious
      and nonanxious patients appear to be equally accurate in their retrospective
      report of symptoms.

PMID- 11315734
TI  - Smoking and moods in adolescents with depressive and aggressive dispositions:
      evidence from surveys and electronic diaries.
AB  - Surveys and electronic diaries were used to examine depressive and extemalizing
      dispositions as they relate to smoking and moods in 170 early adolescents.
      Negative moods were prevalent, with anger and anxiety reported on 26%-60% and
      sadness on 16%-40% of occasions. The risk of smoking, urges to smoke, and alcohol
      intake were elevated in teens with aggressive and depressive dispositions, as
      were diary reports of feeling hassled, angry, and sad. Girls high in depression
      and aggression also reported more anxiety, stress, and fatigue and less happiness
      and well-being than did their peers. For boys, depression seemed to dampen the
      elevated smoking risks associated with externalizing behaviors. Discussion
      focuses on gender differences in personality-smoking linkages, adolescent
      negative affectivity, the unique contributions of survey and diary methods, and
      the promise of targeted preventive interventions such as affect regulation
      training.

PMID- 11315735
TI  - Detection of water quality using simulated satellite data and semi-empirical
      algorithms in Finland.
AB  - The aim of the study was to test the feasibility of the band combination of the
      TERRA MODIS and ENVISAT MERIS instruments for operational monitoring of lakes and
      coastal waters in Finland. Also simulated LANDSAT TM data were tested. Satellite
      bands were simulated using airborne measurements with AISA imaging spectrometer.
      Semi-empirical algorithms with simulated satellite data were tested against field
      observations using regression analysis. Interpretation of chlorophyll a,
      suspended matter, turbidity and secchi-disk depth was included in the analyses.
      The data for this study were gathered in campaigns carried out in May and August
      1997 and August 1998 both for lakes in southern Finland and coastal waters of the
      Baltic Sea. The data set included 85 in situ observations for lakes and 107 for
      coastal waters. Our results show that the band combination to be included in the
      ENVISAT MERIS instrument enables the interpretation of water quality, including
      chlorophyll a concentration using semi-empirical algorithms both for lakes and
      coastal waters. MERIS band 9 centred at 705 nm is proven to be of vital
      importance for the detection of chlorophyll a in local surface waters.

PMID- 11315736
TI  - The effects of variability in the inherent optical properties on estimations of
      chlorophyll a by remote sensing in Swedish freshwaters.
AB  - During late summer of 1997 measurements were made of the inherent optical
      properties in Lake Malaren, Sweden. These included measurements of the total
      particulate absorption, phytoplankton absorption, yellow substance absorption and
      total backscattering. Measurements were also made of concentrations known to
      affect the inherent optical properties; chlorophyll a and suspended particulate
      organic and inorganic matter. At the same time measurements of underwater
      radiance reflectance were made. The above measurements were used to better define
      the relationships between the inherent optical properties and the concentrations
      affecting them. Correlation analyses were also made in order to study covariation
      of the concentrations of suspended and dissolved substances in the data set.
      These relationships were then used to better parameterize a semi-analytical model
      predicting remote sensing reflectance. Multivariate sensitivity analyses showed
      that large variations on the Rr(700-710)/Rr(678-685) ratio vs. chlorophyll
      concentrations could be expected in a heterogeneous environment such as Lake
      Malaren. This could lead to large errors in subsequent estimates of chlorophyll
      concentrations.

PMID- 11315737
TI  - Mapping of the water quality of Lake Erken, Sweden, from imaging spectrometry and
      Landsat Thematic Mapper.
AB  - Hyperspectral data have been collected by the Compact Airborne Spectrographic
      Imager (CASI) and multispectral data by the Landsat Thematic Mapper (TM)
      instrument for the purpose of mapping lake water quality. Field campaigns have
      been performed on Lake Erken in Sweden during the summer of 1997. Water samples
      have been collected and analysed in laboratory. Continuously measured variables
      from a boat have added a spatial dimension to the ground truth dataset. The data
      have been used to construct algorithms, based on remotely sensed data, for the
      retrieval of water quality parameters. The correlation between the continuous
      data and the collected CASI data has been investigated. Algorithms using both the
      point sampling results and the continuous data have been developed. Maps based on
      data from each instrument, showing the distribution of chlorophyll, are
      presented. Problems of having few water sampling stations, and the potential of
      using sub-water optics models are addressed as well. Tests were performed on
      MERIS bands and found useful for mapping chlorophyll and turbidity, and
      algorithms have been suggested for future use with MERIS.

PMID- 11315738
TI  - Statistical analysis of hyperspectral data from two Swedish lakes.
AB  - CASI data has been collected from two lakes in Sweden. In this paper, some
      statistical properties of CASI spectral data have been discussed. Principal
      component analysis is used for assessing the dimensionality of the data and the
      principal components were used for making chlorophyll maps. The quality of the
      reconstruction of the spectra from the principal components was demonstrated.
      Examples of the accuracy of the radiative transfer code 6S in atmospheric
      correction applications have been given. Furthermore, the widths and positions of
      the spectral bands based on the studied dataset were proposed for chlorophyll
      mapping. Robustness aspects of regression models have been discussed. Algorithms
      derived from one lake have been used to map water quality parameters in another
      lake. Algorithms based on principal components, as well as algorithms based on
      image bands, have been used.

PMID- 11315739
TI  - Estimation of radiance reflectance and the concentrations of optically active
      substances in Lake Malaren, Sweden, based on direct and inverse solutions of a
      simple model.
AB  - A semi-analytical model which predicts radiance reflectance just below the water
      surface (Lu/Ed 0-) has been developed and used to predict the spectral
      variability of radiance reflectance in Lake Malaren, Sweden. Radiance reflectance
      is predicted as a function of the optically active substances in the water, which
      include the concentrations of chlorophyll-a + phaeophytin-a, suspended particular
      inorganic material (SPIM), suspended particulate organic material (SPOM), and
      dissolved yellow substances. These substances are linked to the absorption and
      backscattering coefficients through a series of empirical relationships, and
      ultimately radiance reflectance is estimated as a function of the ratio of
      backscattering to absorption. Parameterization of the model, i.e. the development
      of the empirical relationships linking the optically active substances to the
      inherent optical properties (IOPs), is based on both in situ measurements and
      laboratory analyses. We have collected data that allowed us to examine the
      potential variability in radiance reflectance, as predicted by our model, due to
      both variations in the optically active substances, and in the model
      parameterization. Simulations based on a data set collected during the fall of
      1997 from 12 sites, which span a large range in water quality (secchi depth 0.8
      5.0 m), suggest that, with the proper parameterization, the model can accurately
      predict the spectra of radiance reflectance as a function of the concentration of
      optically active substances. Variations in the concentrations of optically active
      substances accounted for a large portion of the total simulated variability in
      radiance reflectance (i.e. that resulting from variations in parameterization and
      in the concentrations of optically active substances). However, the measured
      variability in parameterization could account for up to 50% of the total
      variability in simulated radiance reflectance. This suggests that variability in
      the model parameterization, arising from both real variability and experimental
      error, will limit the use of this model for interpreting remote sensing data.
      Nevertheless, inverse solutions of the model are able to estimate the
      concentrations of chlorophyll, suspended inorganic material (SPIM) and the
      absorption of yellow substances from measured radiance reflectance spectra The
      average error for the 12 sites was a -0.07 for chlorophyll, -0.15 for dissolved
      yellow substances (measured as the absorption at 400 nm) and 0.07 for SPIM, even
      though individual errors could be as great as 50%.

PMID- 11315740
TI  - Comparison of two inversion techniques of a semi-analytical model for the
      determination of lake water constituents using imaging spectrometry data.
AB  - In this study, two different inversion techniques for the determination of
      chlorophyll-a in water were compared by a sensitivity analysis: (i) a matrix
      inversion method, and (ii) a curve-fitting routine. Adding white noise to the
      reflectance spectrum led to clearly better results for the curve-fitting routine.
      If, however, the atmospheric parameter visibility was not exactly known, both
      methods behaved similarly well. The analyses implied that the performance
      depended on the quality of the input spectra, the knowledge of model parameters,
      and also on the inversion methods, even if they were based on the same semi
      analytical model. Of course, not only the uncertainties of model parameters had
      to be considered for the testing of the performance, but also other factors, such
      as processing time, implementation of the inversion algorithm, number of relevant
      parameters, and the application of the method to different times and different
      lakes.

PMID- 11315741
TI  - Detecting chlorophyll, Secchi disk depth and surface temperature in a sub-alpine
      lake using Landsat imagery.
AB  - Some bio-physical parameters, such as chlorophyll a concentration, Secchi disk
      depth and water surface temperature were mapped in the sub-alpine Lake Iseo
      (Italy) using Landsat Thematic Mapper (TM) data acquired on the 7 March 1997. In
      order to adequately investigate the water-leaving radiance, TM data were
      atmospherically corrected using a partially image-based method, and the
      atmospheric transmittance was measured in synchrony with the satellite passage.
      An empirical approach of relating atmospherically corrected TM spectral
      reflectance values to in situ measurements, collected during the satellite data
      acquisition, was used. The models developed were used to map the chlorophyll
      concentration and Secchi disk depth throughout the lake. Both models gave high
      determination coefficients (R2 = 0.99 for chlorophyll and R2 = 0.85 for the
      Secchi disk) and the spatial distribution of chlorophyll concentration and Secchi
      disk depth was mapped with contour intervals of 1 mg/m3 and 1 m, respectively. A
      scene-independent procedure was used to derive the surface temperature of the
      lake from the TM data with a root mean square error of 0.3 degrees C.

PMID- 11315742
TI  - Comparison of remote sensing data, model results and in situ data for total
      suspended matter (TSM) in the southern Frisian lakes.
AB  - Suspended matter plays an important role in water quality management since it is
      related to total primary production and fluxes of heavy metals and
      micropollutants such as PCBs. Synoptic information on suspended matter at a
      regular frequency is difficult to obtain from the routine in situ monitoring
      network since suspended matter is (like chlorophyll) a spatially inhomogeneous
      parameter. This can be solved by the integrated use of remote sensing data, in
      situ data and water quality models. A methodology previously developed for
      integrating information from remote sensing, and models (Vos and Schuttelaar,
      Neth Remote Sensing Board (1995) report 95-19), was applied for the assessment of
      suspended matter concentrations in the southern Frisian lakes in the Netherlands.
      The model is a one-dimensional network model. Remote sensing data (Landsat-TM5
      and SPOT-HRV) were atmospherically corrected and converted to total suspended
      matter maps. The algorithms are based on analytical optical modelling, using the
      in situ inherent optical properties. This methodology enables the development of
      multi-temporal algorithms for estimating seston dry weight concentration in lakes
      from remotely sensed data; thus satellite data can now become an independent
      measurement tool for water management authorities.

PMID- 11315743
TI  - Using a compact airborne spectrographic imager to monitor phytoplankton biomass
      in a series of lakes in north Wales.
AB  - Three lakes in Snowdonia and two on the island of Anglesey were surveyed using a
      Compact Airborne Spectrographic Imager (casi). Water samples for chlorophyll
      measurements and phytoplankton counts were collected at the time of the
      overflight and the optical characteristics of the lakes recorded by a scanning
      spectroradiometer. Spectral measurements in the five lakes showed that their
      optical characteristics were primarily determined by the concentration of
      phytoplankton in suspension. All the lakes were relatively clear, but the more
      productive waters contained small amounts of dissolved organic carbon of
      autochthonous origin. The airborne imaging spectrometer was programmed to measure
      upwelling radiance in eight narrow bands and linear regressions used to compare
      the performance of a selected range of chlorophyll retrieval algorithms. The
      results showed that the most effective algorithms were those based on
      measurements in the blue and green portions of the spectrum. The best single band
      algorithm was centred on 440 nm and explained 75% of the measured variation in
      the concentration of chlorophyll. The best multi-band algorithm was based on
      measurements taken at 560 and 440 nm and accounted for 94% of the recorded
      variation. Chlorophyll maps produced by this algorithm showed that the
      phytoplankton in most of the lakes was homogeneously distributed but surface
      patches of cyanobacteria were detected at one location.

PMID- 11315744
TI  - Validation of satellite data for quality assurance in lake monitoring
      applications.
AB  - The operational application of remote sensing technologies to lake water quality
      monitoring requires products derived from remote sensing to be quantitatively
      self-consistent and have a certified accuracy. Fundamental elements in this
      quality assurance framework are sensor radiometric calibration and atmospheric
      correction models, which are briefly discussed in the paper. In order to evaluate
      the accuracy of present operational techniques to retrieve basic parameters from
      satellite data, such as water-leaving radiance and reflectance, an experiment was
      organised in the frame of SAtellite remote sensing for Lake MONitoring (SALMON),
      a European Union co-funded research project. A series of ship-based radiometric
      and atmospheric measuring campaigns were conducted on Lake Iseo and Lake Garda
      (Italy) together with limnological sampling. Four Landsat-5 Thematic Mapper (TM)
      scenes were acquired during different seasons and simultaneous in situ
      measurements were made. After the radiometric calibration procedure, satellite
      digital images were processed by applying two entirely image-based atmospheric
      correction models. These models account for the effects of both additive
      scattering and multiplicative transmittance effects in the atmosphere on the at
      satellite measured signal. The results achieved using these procedures were
      evaluated by comparing satellite-based estimates with in situ measurements of
      water reflectance. The root mean square difference between Landsat TM-derived
      reflectance values and ground measurements was close to 0.010 reflectance for
      each TM spectral band. Such image-based correction models, requiring no in situ
      field measurements during the satellite overpass, constitute a valid method of
      lake water monitoring.

PMID- 11315745
TI  - Relationship between apparent optical properties and photosynthetic pigments in
      the sub-alpine Lake Iseo.
AB  - The aim of the present study was the evaluation of methods for estimating the
      content of bio-physical parameters in lake water on the basis of spectral
      reflectance measured above water surface, in particular the estimation of
      chlorophyll-a (chl-a) concentrations. Data sets considered refer to some sampling
      point located in the sub-alpine meso-eutrophic Lake Iseo, surveyed six times over
      the period March-July and once in November 1998, as these months were very
      important for the characterization of the springtime algal bloom, which affect
      the lake waters yearly. At each point station, limnological observations
      (chlorophyll, total suspended solids, Secchi disk depth) were conducted
      simultaneously with optical measurements. The latter consisted of water leaving
      radiance measured by means of a spectroradiometer above the water surface;
      moreover, a standard reflector radiance was also measured to obtain the water
      reflectance. Reflectance spectra were transformed according to two well
      documented models and correlated to water quality parameters, to investigate
      their performances as retrieval algorithms under different conditions and
      referring to different analytical methods. Results outline the sensitivity of the
      models to chl-a concentrations, different phytoplankton composition, and the
      sampling depth.

PMID- 11315746
TI  - A hyperspectral model for interpretation of passive optical remote sensing data
      from turbid lakes.
AB  - A hyperspectral model was developed for the interpretation of remote sensing data
      collected above inland waters. Specific absorption and scattering coefficients
      proposed by other authors were not suitable for modelling of the irradiance
      reflectance in 12 studied lakes. Therefore, special studies were carried out to
      estimate absorption and scattering coefficients as well as backscattering
      probability of suspended matter in turbid waters. AC-9 and Li-1800UW results were
      used for these purposes. The algorithms obtained were used to improve the model,
      which was then tested in forward and inverse modes.

PMID- 11315747
TI  - Retrieval of water quality from airborne imaging spectrometry of various lake
      types in different seasons.
AB  - The suitability of the AISA airborne imaging spectrometer for monitoring lake
      water quality was tested in four surveys carried out in southern Finland in 1996
      1998. Altogether, 11 lakes were surveyed and the total number of stations with
      concurrent remote sensing and limnological measurements was 127. The ranges of
      the water quality variables were: the sum of chlorophyll a and phaeophytin a 1
      100 microg l(-1), turbidity 0.4-26 FNU, total suspended solids 0.7-32 mg l(-1),
      absorption coefficient of aquatic humus at 400 nm 1.2-14 m(-1) and secchi disc
      transparency 0.4-7 m. For the retrieval analyses, 24 AISA channels in the 450-786
      nm range with a channel width of 6-14 nm were used. The agreement between
      estimated and observed water quality variables was generally good and R2 for the
      best algorithms was in the range of 0.72-0.90 over the whole dataset. The
      channels used for May were, in most cases, the same as those for August, but the
      empirical parameters of the algorithms were different. After seasonal grouping,
      R2 varied from 0.84 to 0.95. The use of apparent reflectance instead of radiance
      improved the estimation of water quality in the case of total suspended solids
      and turbidity. In the most humic lake, the empirical algorithms tested were
      suitable only for the interpretation of total suspended solids and turbidity.

PMID- 11315748
TI  - A semi-operative approach to lake water quality retrieval from remote sensing
      data.
AB  - A semi-operative approach to retrieve chlorophyll-a concentration from
      airborne/spaceborne spectrometer observations has been developed and tested using
      the airborne imaging spectrometer (AISA) data from 11 lakes located in southern
      Finland. The retrieval approach is empirical and requires nearly simultaneous in
      situ training data on water quality for the determination of regression
      coefficients. However, the training data does not have to be collected from every
      lake under investigation. Instead, the results obtained indicate that reliable
      estimates on the level of chlorophyll-a (chl-a) for an individual lake can be
      achieved without employing in situ data representing this specific lake. This
      enables the estimation of water quality from remotely sensed data for numerous
      lakes with the aid of reference data only for a few selected lakes representing
      the region under investigation. In addition, it is shown that the remotely sensed
      spectrum shape characteristics are highly affected by the trophic and humic state
      of the lake water.

PMID- 11315749
TI  - Analysis on the feasibility of multi-source remote sensing observations for chl-a
      monitoring in Finnish lakes.
AB  - Chlorophyll-a (chl-a) concentration of lake water can be measured with airborne
      (or spaceborne) optical remote sensing instruments. The rmse obtained here with
      empirical algorithms and 122 measurement points was 8.9 microg/l (all points used
      for training and testing). Airborne Imaging Spectrometer for Applications (AISA)
      was used in four lake water quality measurement campaigns (8 measurement days) in
      southern Finland during 1996-1998 with other airborne instruments and extensive
      in situ data collection. As empirical algorithms are employed for chl-a retrieval
      from remote sensing data, temporally varying factors such as surface reflection
      and atmospheric effects degrade the estimation accuracy. This paper analyzes the
      quantitative accuracy of empirical chl-a retrieval algorithms available as
      methods to correct temporal disturbances are either included or excluded. The aim
      is to evaluate the usability of empirical chl-a retrieval algorithms in cases
      when no concurrent reference in situ data are available. Four methods to reduce
      the effects of temporal variations are investigated. The methods are: (1)
      atmospheric correction; (2) synchronous radiometer data; (3) wind speed data; and
      (4) bidirectional scattering model based on wind speed and sun angle data. The
      effects of different correction methods are analyzed by using single-date test
      data and multi-date training data sets. The results show that the use of a
      bidirectional scattering model and atmospheric correction reduces the bias
      component of the measurement error. Radiometer data also appear to improve the
      accuracy. However, if concurrent in situ reference data are not available, the
      retrieval algorithms and correction methods should be improved for reducing the
      bias error.

PMID- 11315750
TI  - Antihypertensive effects of Dorstenia psilurus extract in fructose-fed
      hyperinsulinemic, hypertensive rats.
AB  - We examined the effect of methanol/methylene chloride extract of Dorstenia
      psilurus given by gastric intubation on systolic blood pressure, plasma glucose,
      insulin, cholesterol, triglycerides and creatinine in rats with fructose-induced
      hypertension. Male Wistar rats in groups of 6 animals each were fed fructose-rich
      diets or standard chow for 3 weeks and treated with 100 mg/kg/day or 200
      mg/kg/day of plant extract or vehicle for 3 subsequent weeks. Systolic blood
      pressure was measured every three days using the indirect tail cuff method.
      Systolic blood pressure was higher in fructose-fed rats (142+/-2 mm Hg, p < 0.01)
      compared with the controls (112+/-2 mm Hg), and was lower in Dorstenia psilurus
      treated groups (127+/-2 and 119+/-1 mm Hg for the dose of 100 and 200 mg/kg,
      respectively) compared with the fructose-fed rats. Plasma insulin, cholesterol
      and triglycerides were higher on the fructose-rich diet compared with the
      controls. Plasma insulin and cholesterol were lower in the Dorstenia psilurus
      treated groups. These results suggest that, Dorstenia psilurus treatment could
      prevent and reverse high blood pressure induced by a diet rich in fructose
      probably by improvement of plasma insulin levels. The plant extract might prove
      useful in the treatment and/or prevention of hypertension.

PMID- 11315751
TI  - In vitro dose dependent inverse effect of nantenine on synaptosomal membrane K+-p
      NPPase activity.
AB  - The effect of nantenine, an aporphine alkaloid, on ATPase K+-dependent
      dephosphorylation was evaluated using p-nitrophenylphosphate (p-NPP) as
      substrate. Basal K+-p-NPPase activity was significantly increased with 3 x 10(-4)
      M, remained unchanged with 3 x 10(-6) M, 3 x 10(-5) M but was reduced with 7.5 x
      10(-4) M and 1 x 10(-3) M nantenine, whereas Mg2+-p-NPPase activity was not
      modified. Kinetic studies showed that K+-p-NPPase inhibition by nantenine is
      competitive to KCl but non-competitive to substrate p-NPP, whereas K+-p-NPPase
      stimulation by nantenine is non-competitive to KCl but competitive to p-NPP.
      These data suggest that there may be two acceptor sites for nantenine in p
      NPPase, one eliciting stimulation and the other inhibition of K+-dependent p-NPP
      hydrolysis. Considering the biphasic action of nantenine on seizures and the
      correlation between decreased ATPase activity and seizure development, alkaloid
      anticonvulsant effect observed at low nantenine doses is attributable to the
      stimulation of phosphatase activity whereas the convulsant effect at high
      alkaloid doses seems related to Na+, K+-ATPase inhibition.

PMID- 11315752
TI  - Anthelmintic activity of the stem bark extracts of Berlina grandiflora and one of
      its active principles, Betulinic acid.
AB  - This study examines the anthelmintic activity of a methanol, hexane and
      ethylacetate extracts of Berlina grandiflora and purified betulinic acid, the
      major triterpenoid found in the extract. Caenorhabditis elegans, a free living
      soil nematode was used as in vitro model in the study. A suspension of worms was
      treated with the extracts. After seven days of incubation activity was assessed
      in terms of number of worms exhibiting motiliy. The results showed that methanol,
      hexane and ethylacetate fractions at 500 ppm showed anthelmintic activities in
      the order ethylacetate > methanol > hexane from the alcoholic crude extract. The
      isolated betulinic acid from the ethylacetate fraction at 100 and 500 ppm showed
      strong anthelmintic activities comparable to piperazine. These results confirm
      the traditional use of Berlina grandiflora as an anthelmintic and indicate that
      betulinic acid is the active component.

PMID- 11315753
TI  - Molluscicidal properties of some species of Annona.
AB  - In search for plant molluscicides for the vector control of schistosomiasis,
      ethanolic extracts from different parts of six species of the Annonaceae family
      were evaluated against adult forms and egg masses of Biomphalaria glabrata.
      Results from accurate experiments indicate that the majority of analyzed extracts
      possess properties lethal to Biomphalaria glabrata, some of them with significant
      LD90 values (< 20 ppm), as showed for Annona crassiflora M: [pulp and seed (LD50
      = 13.21), steem (2.34), root bark (3.79)], Annona glabra L. [seed (17.02)],
      Annona muricata [leaf (8.75)]. Emphasis is held mainly into Annona muricata L.
      (leaf) and Annona squamosa Veil. (root) for presenting additional toxicity toward
      snail egg masses.

PMID- 11315754
TI  - Chemistry and bioactivity of Raulinoa echinata Cowan, an endemic Brazilian
      Rutaceae species.
AB  - The hexane extract of the stems of Raulinoa echinata afforded the sesquiterpenes
      germacrene D (6), 1beta,6alpha-dihydroxy-4-(15)-eudesmene (4) and oplopanone (5);
      the triterpenes squalene, isomultiflorenol (7), isobauerenol (8) and friedelin
      (9); the protolimonoids melianone (2) and melianodiol (3); and the pyranocoumarin
      3-(1'-1'-dimethylallyl)-lomatin (1), which has not been reported previously as a
      natural product; together with beta-sitosterol. The hexane extract and some of
      these compounds were assayed in vitro against trypomastigote forms of Trypanosoma
      cruzi. Brine shrimp lethality and antimicrobial activities of the crude extract
      and pure compounds were also evaluated.

PMID- 11315755
TI  - Indian medicinal plants as antiradicals and DNA cleavage protectors.
AB  - Celastrus paniculatus L. (Celastraceae) (CP), Picrorhiza kurroa L.
      (Scrophulariaceae) (PK) and Withania somnifera L. (Solanaceae) (WS) are Indian
      medicinal plants having a remarkable reputation, as a factor of health care,
      among the indigenous medical practitioners. The plants exhibit varying degrees of
      therapeutic value some of which useful in the treatment of cognitive dysfunction,
      epilepsy, insomnia, rheumatism, gout, dyspepsia. In this work, we have
      investigated the free radical scavenging capacity of methanolic extracts from CP,
      PK, WS and the effect on DNA cleavage induced by H2O2 UV-photholysis. In
      addition, we investigated whether these plant extracts are capable of reducing
      the hydrogen peroxide-induced cytotoxicity and DNA damage in human non
      immortalized fibroblasts. These extracts showed a dose-dependent free radical
      scavenging capacity and a protective effect on DNA cleavage; methanolic extracts
      from PK was more active than extracts from CP and WS. These results were
      confirmed by a significant protective effect on H2O2-induced cytoxicity and DNA
      damage in human non-immortalized fibroblasts. These antioxidant effects of active
      principle of CP, PK and WS may explain, at least in part, the reported anti
      stress, immunomodulatory, cognition-facilitating, anti-inflammatory and antiaging
      effects produced by them in experimental animal and in clinical situations and
      may justify the further investigation of their other beneficial biological
      properties.

PMID- 11315756
TI  - Evidence for toxic effects of alkylphenols from Ginkgo biloba in the hen's egg
      test (HET).
AB  - Extracts from the leaves of the Gingko tree (Ginkgo biloba L.) are
      therapeutically used for the treatment of peripheral and cerebral vascular
      disorders as well as multi-infarct or Alzheimer-type dementia. As constituents
      with potential contact allergenic and toxic properties in crude Ginkgo extracts a
      group of alkylphenols (e.g., ginkgolic acids, ginkgol, bilobol) has been
      described. Thus, for reasons of drug safety a maximal concentration (< or = 5
      ppm) of ginkgolic acids is requested by the Monograph of the Commission E of the
      former German Federal Health Agency (Bundesgesundheitsamt, BGA). During
      production of the standardized Ginkgo extract EGb 761, alkylphenols are largely
      eliminated as water insoluble compounds (decanter sludge) from the primary
      acetone extract. To further assess the adverse properties of alkylphenols,
      different fractions derived from the decanter sludge were evaluated for their
      embryotoxic effects in the hen's egg test (HET). A fraction enriched for
      ginkgolic acids (16%) and biflavones (6.7%) was found to induce death of 50% of
      the chick embryos (LD50) at a dose of 1.8 mg/egg (approximately/= 33 ppm). A
      similar strong lethal effect (LD50: 3.5 mg/egg; 64 ppm) was oberserved for a
      fraction which contained 58% ginkgolic acids but less than 0.02% biflavones. In
      contrast, an extreme low toxic potential (LD50: 250 mg/egg or 4540 ppm) was
      established for a fraction containing 16% biflavones and 1% ginkgolic acids.
      Thus, the present investigations confirm the high toxic potential of ginkgolic
      acids, although it can not be excluded that biflavones or some other constituents
      in the different fractions may amplify the adverse effect of these substances.
      Since no contribution of alkylphenols to the therapeutic efficacy of Ginkgo
      extracts has been confirmed and their elimination during the manufacturing
      process does not cause technical problems, these results further support the
      requirement for the completest possible removal of these compounds under
      toxicological considerations.

PMID- 11315757
TI  - The influence of ultraviolet radiation on the content of pharmacologically active
      taxoids in yew tissues.
AB  - The aim of the work was the investigation of the influence of UV radiation on the
      taxoids contents in yew tissues. The experiment was performed using Taxus baccata
      var. Aurea Corr. twigs irradiated with UV C (lambda = 254 nm) and UV A (lambda =
      366 nm) in comparison to control samples. Multistep procedure of sample
      preparation was applied before the analysis of paclitaxel and 10-DAB III: SPE
      using alumina - for purification from the chlorophylles, waxes and polar balasts
      as well as zonal micropreparative TLC on silica - for isolation of partially
      separated fractions. The quantitation of some taxoids in the isolated fractions
      was performed using RP-HPLC procedure in system C18/acetonitrile + water. The
      experiments with UV-A and especially UV-C radiation showed changes in
      concentrations of paclitaxel and its precursor-10-deacetylbaccatin III. The
      results can be utilized to increase the yield of the taxoids isolated for
      medicinal and practical purposes.

PMID- 11315758
TI  - Evaluation of biological activity of crude extracts from plants used in Yucatecan
      traditional medicine part I. Antioxidant, antimicrobial and beta-glucosidase
      inhibition activities.
AB  - Bioactivity of extracts from leaves, stems and roots of twelve plants commonly
      used in Yucatecan traditional medicine were evaluated in four bioassays. Crude
      extracts from ten plants showed significant activity in the inhibition of
      bleaching of beta-carotene assay, while thirteen extracts showed activity in the
      reduction of 2, 2- diphenyl-1-picrylhydrazyl radical (DPPH) assay. In the
      antimicrobial bioassay, the major activity was presented by the root extract of
      Jatropha gaumeri and in the beta-glucosidase inhibition activity assay the
      strongest activity was observed in the stem and root extracts of Solanum hirtum.

PMID- 11315759
TI  - Incidence and clinical relevance of the interactions and side effects of
      Hypericum preparations.
AB  - Observational studies with preparations of St. John's wort have recorded an
      incidence of adverse events (AE) among those treated of between 1 and 3%. This is
      some ten times less than with synthetic antidepressants. The most common adverse
      events (1 per 300000 treated cases) among the spontaneous reports in the official
      register concern reactions of the skin exposed to light. Investigations in
      volunteers have shown that the threshold dose for an increased risk of
      photosensitisation is about 2-4 g/day of a usual commercial extract (equivalent
      to approximately 5-10 mg of the hypericin that causes the phenomenon). In view of
      the newly observed side effects and interactions, the following additional
      restrictions on use appear justified: as with all preparations in this group of
      indications, hypericum preparations must not be taken at the same time as other
      antidepressants. If co-medication with coumarin-type anticoagulants is
      unavoidable, it must only be undertaken provided the physician closely monitors
      clotting parameters. Co-medication with ciclosporin and indinavir, and for the
      time being, other protease inhibitors used in anti-HIV treatment, is absolutely
      contraindicated. Without exception, all preparations of St. John's wort must only
      be available through pharmacies.

PMID- 11315760
TI  - Antidiabetic activity of a xanthone compound, mangiferin.
AB  - Mangiferin (MF) isolated from Anemarrhena asphodeloides Bunge rhizome, was tested
      for antidiabetic activity in KK-Ay mice, an animal model of type-2 diabetes. MF
      lowered the blood glucose level of KK-Ay mice 3 weeks after oral administration
      (p < 0.01). However, no effect on the blood glucose level in normal mice was
      seen, indicating that MF could be useful in treating type-2 diabetes. In
      addition, MF improved hyperinsulinemia and, on insulin tolerance test, reduced
      blood glucose levels of KK-Ay mice. From these findings, it seems likely that MF
      exerts its antidiabetic activity by decreasing insulin resistance.

PMID- 11315761
TI  - Hypoglycemic and antihyperglycemic activity of Syzygium alternifolium (Wt.) Walp.
      seed extracts in normal and diabetic rats.
AB  - Aqueous, ethanolic and hexane fractions of Syzygium alternifolium seeds were
      prepared and given different doses of these extracts individually to different
      batches of rats (both normal and alloxan diabetic rats) after an overnight fast.
      The blood glucose levels were measured at 0, 1, 3, 5 and 7 hours after the
      treatment. The aqueous extract of Syzygium alternifolium at a dosage of 0.75 g/kg
      b.w. is showing maximum blood glucose lowering effect in both normal and alloxan
      diabetic rats. The ethanol and hexane fractions are also showing hypoglycemic and
      antihyperglycemic activity, but the effect is significantly less than that of
      aqueous extract. The antihyperglycemic activity of Syzygium alternifolium seed
      was compared with the treatment of Glibenclamide.

PMID- 11315762
TI  - Gastroprotective effect of aparisthman, a diterpene isolated from Aparisthmium
      cordatum, on experimental gastric ulcer models in rats and mice.
AB  - Aparisthmium cordatum (Juss.) Bail. (Euphorbiaceae), known in the State of Para,
      Brazil as "ariquena queimosa", is a medium-sized tree which is native to the
      North Brazilian coastal region. Previous phytochemical studies of the bark of A.
      cordatum yielded a furan diterpenoid with a clerodane skeleton, called
      aparisthman. Recently, we reported the antiulcerogenic activity of trans
      dehydrocrotonin (DHC), a furan diterpene isolated from Croton cajucara bark, in
      different ulcerogenic models in mice and rats. The aim of the present study was
      to assess the possible antiulcerogenic activity of aparisthman. When previously
      administered (p.o.) at the dose of 100 mg/kg(-1), aparisthman reduced
      significantly (p < 0.01) gastric injury induced by the indomethacin/bethanechol
      (71%), ethanol (71%), pylorus ligature, (59%) and hypothermic restraint-stress
      models (50%), in mice and rats. In the HCl/ethanol-induced gastric ulcer model in
      mice, at oral doses of 100 and 250 mg/kg(-1), aparisthman from A. cordatum
      reduced significantly (p < 0.001) the formation of gastric lesions by 59% and
      66%, respectively, as compared with control. In the pylorus-ligature model,
      aparisthman (p.o.) decreased the volume of gastric juice as compared with control
      (p < 0.001). When aparisthman (100 mg/kg(-1)) was administered intraduodenally to
      mice, significant modifications were found, such as a decrease in gastric acidity
      as compared with control. In the animals pre-treated with aparisthman, free mucus
      production increased by 19% in the gastric mucosa (p < 0.05). The results suggest
      that aparisthman from A. cordatum presents a significant anti-ulcer effect when
      assessed in these induced ulcer models. Although the mechanism underlying this
      antiulcerogenic effect remains unknown, it seems to be related to an increase of
      the defensive mechanisms of the stomach such as prostaglandin synthesis and mucus
      production. The good yield of aparisthman obtained from A. cordatum, as well as
      its antiulcerogenic activity, suggest that this compound should be submitted to
      pharmacological research as a potential new antiulcerogenic drug.

PMID- 11315763
TI  - The role of Pax6 in brain patterning.
AB  - Pax6 g ene encodes a transcription factor that plays a pivotal role in various
      aspects of brain development. Here I review the molecular and cellular mechanisms
      of how the early brain is patterned, and introduce recent studies on the role of
      Pax6 in brain patterning, neuronal specification, neuronal migration and axonal
      extension.

PMID- 11315764
TI  - The current status of gynecological laparoscopic surgery in educational
      facilities in Japan.
AB  - A questionnaire survey was administered by Tohoku University hospital to
      investigate the current status of gynecological laparoscopic operations in
      teaching hospitals in which residents were trained as obstetricians and
      gynecologists. Thirty-eight senior doctors in 18 hospitals were sent a postal
      questionnaire. The response rates of facilities and doctors were 94.4% and 76.3%
      respectively. Diagnostic and operative laparoscopy was performed in all of the
      hospitals surveyed, however only a few hospitals performed more than 100
      laparoscopies per year, and many surgeons did not perform advanced laparoscopic
      operations including hysterectomy, myomectomy and lymphadenectomy. Half of the
      doctors performed minilaparotomy, which is a so-called "open" technique. The
      standard surgical style involved the use of a carbon dioxide (CO2)
      pneumoperitoneum and an endoscope 10 mm in diameter. Unipolar endocoagulating
      instruments were generally used for hemostasis and incision. Most of the doctors
      surveyed thought that operative laparoscopy would become a necessary procedure in
      gynecological field, and half of them hoped to receive training in the technique.
      Instruction of expert endoscopic surgeons is necessary, especially in teaching
      hospitals, for the spread of safe and advanced laparoscopic surgery. An
      educational and training system for established surgeons as well as for young
      residents is urgently needed in Japan.

PMID- 11315765
TI  - Infrequent APC mutations in serrated adenoma.
AB  - In 1990, Longacre and Fenoglio-Preiser introduced "serrated adenoma (SA)"
      combining architectural and cytological features of hyperplastic polyp and
      adenomatous epithelium. It has been reported that intramucosal carcinoma occurs
      in 10% of SAs. Although there have been many reports on SAs, its histogenesis and
      natural history still remain unknown. To clarify the genetic changes in SA, APC
      mutations in 28 SAs, 4 adenocarcinomas in/with SAs, 12 tubular adenomas (TAs) and
      10 adenocarcinomas in/with TAs were evaluated in the present study. After
      polymerase chain reaction single strand conformation polymorphism (PCR-SSCP)
      analyses, gene mutations were confirmed by direct sequencing. No APC mutation was
      detected in adenocarcinomas in/with SAs, and only one SA without adenocarcinoma
      (3.8%) was found to be positive for APC gene mutation, whereas the mutations were
      found in 66.7% of TAs and in 50% of adenocarcinomas in/with TAs. The frequency of
      APC gene mutation in SAs was significantly lower than that in control sporadic
      TAs. These findings suggest that SAs are genetically different from TAs.

PMID- 11315766
TI  - Changes in glycosaminoglycan, galactosyltransferase-I, and sialyltransferase
      during rat liver regeneration.
AB  - After partial hepatectomy, the liver is capable of complete restoration to its
      normal size. The extracellular matrix, which surrounds the cells, plays important
      roles in this regeneration. Glycosaminoglycans (GAGs), which are components of
      the extracellular matrix, interact with several other matrix components and
      growth factors, and are involved in hepatocyte growth. In this study, the content
      of heparan sulfate, a major GAG in rat liver, reached a minimum at 12 hours after
      partial hepatectomy. Galactosyltransferase-I activity, related to the synthesis
      of GAGs, and sialyltransferase activity, related to the synthesis of
      glycoconjugates, reached a minimum at 6 hours. The serum and liver contents of
      hyaluronic acid reached a maximum at 1 day and returned gradually to their
      preoperative levels. These results suggest that polysaccharide synthesis was
      decreased in the Golgi apparatus of hepatocytes at the beginning of regeneration,
      and that hyaluronic acid degradation decreased in the lysosomes of hepatocytes.
      The ability to synthesize polysaccharides recovered ahead of the ability to
      degrade hyaluronic acid. The changes in these GAGs with time in the early
      regeneration period might play an important role in organ regeneration.

PMID- 11315767
TI  - Variants within the "a" determinant of HBs gene in children and adolescents with
      and without hepatitis B vaccination as part of Thailand's Expanded Program on
      Immunization (EPI).
AB  - A total of 2229 children selected from five distinct areas of Thailand were
      screened for HBs antigen (HBsAg) by ELISA. Out of 51, forty-nine HBsAg-positive
      children were further examined for HBV-DNA by the polymerase chain reaction,
      utilizing the region of the hepatitis B Virus (HBV) genome encoding the major
      antigenic epitopes of hepatitis B surface antigen. Direct automated sequencing of
      the "a" determinant region revealed 11 of 49 children to display variable
      mutations. The vaccinated and nonvaccinated children had amino acid variants
      clustered between residues 120 and 160. Mutations between residues 120 and 160
      were found at higher frequency in the vaccinated group (4/13; 30.8%) than in the
      nonvaccinated group (7/36; 19.4%), but this was not statistically significant.
      Infections with new HBV variants are contracted either vertically or horizontally
      within the group having received the vaccine, a finding confirmed by the presence
      of amino acid substitutions critical for immune escape. Hence, neither vaccine
      nor IgG has any apparent effect on those variants and the children turn into HBV
      carriers. However, the current vaccination program still efficiently protects
      perinatal transmission of HBV and unless long term studies lead us to conclude
      otherwise, inclusion of the variant strain(s) into a new vaccine formulation is
      not deemed necessary.

PMID- 11315768
TI  - Nephron distribution of total low Km cyclic AMP phosphodiesterase in mouse, rat
      and rabbit kidney.
AB  - The activity of cAMP degradation enzyme, cAMP phosphodiesterase (cAMP PDE), in
      renal tubules is a critically important factor in determining cellular cAMP
      levels, particularly in response to hormones. In this study we examine the
      nephron distribution of cAMP PDE activity in the mouse, rat and rabbit kidney and
      important cellular regulators of cAMP PDE, namely calmodulin and adenosine
      triphosphate (ATP). We assayed total low Km cAMP PDE in microdissected tubule
      segments, using 10(-6) M (3H) cAMP as a substrate. Activities were expressed in
      fentomol cAMP hydrolyzed per minute per mm tubular length or per one glomerulus.
      The content of ATP was measured in outer medullary collecting duct and medullary
      thick ascending limb of Henle's loop with microbioluminescence assay using
      firefly luciferase. In mouse kidney, cAMP PDE was significantly higher in all
      tubular segments compared to glomerulus. Proximal convoluted tubule, proximal
      straight tubule, medullary thick ascending limb of Henle's loop (mTAL), and outer
      medullary collecting duct (OMCD) had intermediated activity. Greater cAMP PDE
      activity was detected in cortical ascending limb of Henle's loop (cTAL), cortical
      collecting duct and in distal convoluted tubule (DCT). The highest activity was
      found in connecting tubules. In rat, nephron distribution of cAMP PDE activities
      was similar to mouse, except that activity in glomeruli was higher than in mouse
      glomeruli. In rabbit, nephron distribution of cAMP PDE activities was different
      from those of mouse and rat. There was no single prominent segment with high cAMP
      PDE activity. DCT and cTAL showed low enzyme activity. Overall, the highest cAMP
      PDE activities were measured in the mouse and the lowest were measured in the
      rabbit nephrons, with those of rat nephron showing an intermediate activity. The
      maximum effective dose of the calmodulin antagonist, trifluoperazine (200
      microM), inhibited cAMP PDE in all nephron segments from the rat kidney. However,
      there is no statistical significance of its inhibition among nephron segments. In
      OMCD and mTAL of the rat kidney, cAMP PDE activity was inhibited by ATP (5 mM to
      approximately 10 mM) which is far beyond the physiological concentartion of ATP
      in normal epithelial cell. Actual determinations of ATP in mTAL and OMCD were 0.1
      mM and 0.17 mM, respectively. These observations show that distal segments of
      tubules have more active catabolism of cAMP than proximal segments. cAMP PDE in
      each nephron segment appear to be almost equally dependent on trifluoperazine
      sensitive pathway that may reflect the Ca2+-calmodulin system. Cellular
      concentration of ATP might not be involved in the regulation of the total low Km
      cAMP PDE activity in rat mTAL and OMCD.

PMID- 11315769
TI  - Closed-loop control using a stretch sensor for restoration of standing with
      functional electrical stimulation in complete paraplegia.
AB  - A closed-loop control system for standing with functional electrical stimulation
      (FES) using percutaneous intramuscular electrodes in complete paraplegia is
      described. The system consisted of ultrafine percutaneous intramuscular
      electrodes, a 32-channel stimulator and a stretch sensor with active current
      control to detect knee buckling. The closed-loop control system was applied in a
      T8 completely paraplegic patient. Compared to the stretch sensor with a wide use
      flexible goniometer for direct current control during standing, the stretch
      sensor was superior to the flexible goniometer in both ease of use and response.
      The average time delay from the start of knee buckling until the sensor turned on
      was 0.56+/-0.19 seconds (Mean+/-S.D.) in the goniometer and 0.21+/-0.06 seconds
      in the stretch sensor. The average time delay from the start of knee buckling
      until the recovery from knee buckling was 1.01+/-0.05 seconds in the goniometer
      and 0.78+/-0.06 seconds in the stretch sensor. The continuous standing ability of
      the patient increased from 12 minutes with open-loop stimulation to 30 minutes
      with the closed-loop control. No complications such as falling occurred during
      clinical use. This system prevented falling due to knee buckling during standing
      and prolonged upright activities in complete paraplegics.

PMID- 11315770
TI  - Element concentrations in urine of patients suffering from chronic arsenic
      poisoning.
AB  - In order to know the element levels in the urine of patients with chronic arsenic
      poisoning caused by arsenic assimilated from burning coal via air and food, we
      investigated various elements in the urine of 16 patients with this disease and
      16 controls living in the same county in Guizhou Province of China.
      Concentrations of 25 elements (Al, As, Ba, Be, Bi, Ca, Cd, Cr, Cu, Fe, Ga, Mg,
      Mn, Mo, Ni, P, Pb, Rb, Sb, Se, Sn, Sr, Ti, V and Zn) were determined by an
      inductively coupled plasma mass spectrometer or an inductively coupled plasma
      atomic emission spectrometer. The average concentrations of Cu, Ga and Sn as well
      as As in the patients were significantly higher, and those of Cr, Rb, Sr and Ti
      in the patients were significantly lower than the control values. Al, Ba, Mn, Ni
      and Se were under detection limit in the patients, though they could be detected
      in the controls. There were no positive correlations between the concentration of
      As and the concentrations of other elements, including Cu, Ga and Sn in the
      patients. The results of this study suggest that As from burning coal might
      influence the urinary excretion of some elements.

PMID- 11315771
TI  - Prednisolone sodium succinate down-regulates BSAP/Pax5 and causes a growth arrest
      in the Nalm6 pre-B cell line.
AB  - Glucocorticoids (GCs) induce growth arrest and apoptosis of B lineage cells,
      especially pre-B and immature B cells, but little is known about this mechanism.
      Since B cell-specific activator protein (BSAP) encoded by the Pax5 gene is an
      essential transcription factor for B-cell proliferation, we have investigated the
      effect of prednisolone sodium succinate (Pss) on BSAP expression in several human
      leukemic B lineage cell lines. Pss caused growth arrest of Nalm6 (pre-B) cells,
      but this is not the case for 207 (pro-B) and Raji (mature B) cells. In Nalm6
      cells, the growth rate and the amount of BSAP bound to its recognition sequence
      decreased in proportion to the Pss dose. Pss also reduced the expression level of
      BSAP as well as of Pax5 mRNA. These data suggest that the suppression of
      Pax5/BSAP may be involved in the GCs-induced growth arrest of pre-B cells.

PMID- 11315772
TI  - A patient with exacerbation of idiopathic pulmonary fibrosis which was resolved
      probably due to the coexisting hyperbilirubinemia?
AB  - This report presents the case of a patient with corticosteroid and
      cyclophosphamide resistant exacerbation of idiopathic pulmonary fibrosis (IPF),
      which was definitely resolved in accordance with increased levels of serum
      conjugated bilirubin due to biliary tract obstruction. Histological examination
      of the lung showed an accumulation of bile pigments in the alveolar mural
      tissues, especially in the cytoplasm of the alveolar macrophages, which play
      crucial roles in the development of IPF. This case suggests that bile pigments
      have some important roles in tissue protection against inflammatory damage in
      IPF, and may illustrate an important key for treatment of this fatal disorder.

PMID- 11315773
TI  - Entrapment of the sensory branch of the radial nerve (Wartenberg's syndrome): an
      unusual cause.
AB  - Isolated neuropathy of the cutaneous branch of the radial nerve is a rarely
      recognized pathology. It was described in 1932 by Wartenberg, who suggested the
      name cheiralgia paraesthetica. The syndrome is described as known the entrapment
      of the superficial branch of the radial nerve. Many different etiologic factors
      for chronic nerve entrapment have been described, however our case has an unusual
      cause. A 52 year old man had pain and paresthesia in the area over the lateral
      aspect of the wrist, thumb and first web six months after Colles' fracture. The
      patient underwent bony spike resection after five months with ineffective
      conservative treatment. He has satisfied after this operation. The case was
      presented because of disappearing his preoperative complaints after the operation
      with respect to Wartenberg's syndrome constituted a rare cause of bone spike
      which has not been mentioned in the literature.

PMID- 11315774
TI  - Acute cholestatic hepatitis caused by a probable allergic reaction to paracetamol
      in an adolescent.
AB  - We reported on an adolescent who suffered from cholestatic hepatitis after taking
      a low dose of paracetamol. It was suspected that the condition was brought about
      by an allergic reaction to paracetamol. Paracetamol is one of the representative
      intrinsic hepatotoxic drugs. There have been only a few reports on liver damage
      due to an allergic reaction to paracetamol. There is a need to call attention to
      this particular reaction.

PMID- 11315775
TI  - Percutaneous screw fixation or cast immobilization for nondisplaced scaphoid
      fractures.
AB  - BACKGROUND: Nondisplaced scaphoid fractures treated with prolonged cast
      immobilization may result in temporary joint stiffness and muscle weakness in
      addition to a delay in return to sports or work. Fixation of scaphoid fractures
      with a percutaneous cannulated screw has resulted in a shorter time to union and
      to return to work or sports. The purpose of this prospective, randomized study
      was to compare cast immobilization with percutaneous cannulated screw fixation of
      nondisplaced scaphoid fractures with respect to time to radiographic union and to
      return to work. METHODS: Twenty-five full-time military personnel with an acute
      nondisplaced fracture of the scaphoid waist consented to be randomized to either
      cast immobilization or fixation with a percutaneous cannulated Acutrak screw
      (Acumed, Beaverton, Oregon) for the purpose of this study. Time to fracture
      union, wrist motion, grip strength, and return to work as well as overall patient
      satisfaction at the time of a two-year follow-up were evaluated. RESULTS: Eleven
      patients were randomized to percutaneous cannulated screw fixation, and fourteen
      were randomized to cast immobilization. The average time to fracture union in the
      screw fixation group was seven weeks compared with twelve weeks in the cast
      immobilization group (p = 0.0003). The average time until the patients returned
      to work was eight weeks compared with fifteen weeks in the cast immobilization
      group (p = 0.0001). There was no significant difference in the range of motion of
      the wrist or in grip strength at the two-year follow-up evaluation. Overall
      patient satisfaction was high in both groups. CONCLUSIONS: Percutaneous
      cannulated screw fixation of nondisplaced scaphoid fractures resulted in faster
      radiographic union and return to military duty compared with cast immobilization.
      The specific indications for and the risks and benefits of percutaneous screw
      fixation of such fractures must be determined in larger randomized, prospective
      studies.

PMID- 11315776
TI  - Overtightening of the ankle syndesmosis: is it really possible?
AB  - BACKGROUND: Many surgeons and orthopaedic references recommend that fixation of a
      disrupted distal tibiofibular syndesmosis be performed with the ankle in
      dorsiflexion to avoid overtightening and subsequent restriction of ankle
      dorsiflexion. This recommendation is based in large part on one cadaveric study
      without clinical correlation. The purpose of the present study was to examine
      whether overtightening of the syndesmosis limits maximal ankle dorsiflexion.
      METHODS: Nineteen cadaveric ankles were used for the study. Each ankle was tested
      for the initial range of motion after release of the Achilles tendon proximal to
      the ankle joint. All capsular and ligamentous structures remained intact.
      Kirschner wires were placed in the tibia and talus. The angle between the wires
      with the ankle maximally dorsiflexed was measured before and after syndesmotic
      compression. Syndesmotic compression was achieved with a 4.5-mm lag screw with
      the ankle in plantar flexion. RESULTS: There was no difference between the values
      for maximal dorsiflexion before and after syndesmotic compression. CONCLUSIONS:
      Syndesmotic compression in and of itself does not diminish ankle dorsiflexion in
      a cadaveric model. CLINICAL RELEVANCE: Maximal dorsiflexion of the ankle during
      syndesmotic fixation is not required in order to avoid loss of dorsiflexion. It
      is likely that the most important aspect of syndesmotic fixation is anatomic
      reduction of the syndesmosis and that the degree of ankle dorsiflexion during
      fixation is not important.

PMID- 11315777
TI  - The economic cost of hip fractures among elderly women. A one-year, prospective,
      observational cohort study with matched-pair analysis. Belgian Hip Fracture Study
      Group.
AB  - BACKGROUND: We conducted a prospective study to assess the costs of initial
      hospitalization for a first hip fracture and to evaluate the excess costs
      attributable to the hip fracture during the one-year period following hospital
      discharge. METHODS: This investigation was designed as a one-year prospective
      cohort study with matched-pair analysis. Elderly women who were receiving care
      for a first hip fracture at four Belgian hospitals were matched, with respect to
      age and residence, with women (control subjects) with no history of hip fracture
      who lived in the same neighborhood. The initial hospitalization costs were
      tabulated from the hospital invoices. To estimate the costs during the year after
      hospital discharge, health-care services utilized by the hip-fracture patients
      and by the control subjects were recorded. We used the official reimbursement
      rates to assign a cost to these services, and the results are reported in United
      States dollars. RESULTS: The mean age of the 159 patients who had a hip fracture
      was 79.3 years, and that of the 159 control subjects was 78.7 years. The total
      mean cost of the initial hospitalization was $9534 for the hip-fracture patients.
      The total direct costs during the year after discharge averaged $13,470 for the
      hip-fracture patients and $6170 for the control subjects. Thus, the excess direct
      cost during the one-year period following hospital discharge averaged $7300 for
      the hip-fracture patients. The largest cost differences were attributable to
      nursing-home stays (31%), rehabilitation-center stays (31%), hospitalizations
      (16%), and home physical-therapy services (14%). Two-fifths of the excess costs
      were spent during the three months following hospital discharge. Moreover, we
      observed a shift in resource utilization after hospital discharge. CONCLUSIONS:
      Our one-year prospective study demonstrated that the costs of treating a hip
      fracture patient are about three times greater than those of caring for a patient
      without a fracture. This study also highlights the savings to society if a hip
      fracture can be avoided.

PMID- 11315778
TI  - Titanium particles stimulate bone resorption by inducing differentiation of
      murine osteoclasts.
AB  - BACKGROUND: Loosening of orthopaedic implants is mediated by cytokines that
      elicit bone resorption and are produced in response to phagocytosis of implant
      derived wear particles. This accelerated bone resorption could be due to
      increased osteoclastic activity, survival, or differentiation. Although a number
      of in vitro studies have shown that wear particles increase osteoclastic
      activity, the increase was less than twofold in all cases. The objective of the
      current study was to test the hypothesis that wear particles stimulate bone
      resorption by inducing osteoclast differentiation. METHODS: Conditioned media
      were prepared from murine marrow cells or human peripheral blood monocytes
      incubated in the presence or absence of titanium particles. The effects of
      conditioned media on osteoclast differentiation were examined with use of a
      recently developed assay in which osteoclast precursors are co-cultured with
      mesenchymal support cells. RESULTS: The present study showed that titanium
      particles induced both murine marrow cells and human peripheral blood monocytes
      to produce factors that stimulated osteoclast differentiation. The mean increase
      in osteoclast differentiation was 29.3+/-9.4-fold. The stimulation of osteoclast
      differentiation led to a parallel increase in bone resorption. The amount of
      stimulation was regulated in a dose-dependent manner by the concentration of both
      titanium particles and conditioned media. The stimulation of osteoclast
      differentiation required interactions between the cells and the particles
      themselves and, therefore, was not due to metal ions, soluble contaminants
      released from the particles, or submicrometer particles. In contrast, conditioned
      media from control cells incubated in the absence of titanium particles had no
      detectable effect on any of the examined parameters. CONCLUSIONS: The present
      study showed that titanium particles stimulate in vitro bone resorption primarily
      by inducing osteoclast differentiation. In contrast, the titanium particles had
      only small effects on osteoclast activity or survival.

PMID- 11315779
TI  - Treatment of severely comminuted intra-articular fractures of the distal end of
      the radius by open reduction and combined internal and external fixation.
AB  - BACKGROUND: Severely comminuted AO type-C3 intra-articular fractures of the
      distal end of the radius are difficult to treat. Failure to achieve and maintain
      nearly anatomic restoration can result in pain, instability, and poor function.
      We report the results of a retrospective study of the use of a standard protocol
      of open reduction and combined internal and external fixation of these fractures.
      METHODS: Seventeen of twenty-five patients treated with the protocol were
      available for follow-up evaluation. Six had an AO type-C3.1 fracture; eight, type
      C3.2; and three, type-C3.3. Eleven fractures required a dorsal buttress plate
      and/or a volar buttress plate, and eleven required bone-grafting. The mean time
      until the external fixator was removed was seven weeks. RESULTS: At a mean of
      thirty months postoperatively, the mean arc of flexion-extension was 72% of that
      on the uninjured side and the mean grip strength was 73% of that on the uninjured
      side. The mean articular step-off was 1 mm, the total articular incongruity (the
      gap plus the step-off) averaged 2 mm, and the radial length was restored to a
      mean of 11 mm. Thirteen patients had less than 3 mm of total articular
      incongruity. Arthritis was graded as none in three patients, mild in ten,
      moderate in three, and severe in one. According to the Gartland and Werley
      demerit-point system, ten of the patients had a good or excellent result.
      According to the modified Green and O'Brien clinical rating system, five had a
      good or excellent result. One patient had a fracture collapse requiring wrist
      fusion, one had reflex sympathetic dystrophy, and three had minor Kirschner-wire
      related problems. Total articular incongruity immediately postoperatively had a
      moderately strong correlation with the outcome as assessed with both clinical
      rating systems (r = 0.70 and 0.74 for the Gartland and Werley system and the
      Green and O'Brien system, respectively; p<0.05). CONCLUSIONS: Open reduction and
      combined internal and external fixation of AO type-C3 fractures can restore
      radiographic parameters to nearly normal values, maintain reduction throughout
      the period of fracture-healing, and provide satisfactory functional results.

PMID- 11315780
TI  - Contact mechanics of normal tarsometatarsal joints.
AB  - BACKGROUND: The current treatment of tarsometatarsal joint injuries is associated
      with suboptimal long-term results. The objective of the present study was to
      measure the contact mechanics of the tarsometatarsal joints in normal adult
      cadaveric feet in order to develop a foundation for more effective treatment.
      METHODS: Six fresh cadaveric lower legs and feet were subjected to four different
      axial compressive loads (0.5, 1.0, 1.5, and 2.0 times body weight) at each of
      five different positions. For each position, load, and tarsometatarsal joint, the
      contact pressures and areas were measured with use of pressure-sensitive film.
      Contact forces were calculated from the ratio of pressure to area. Contact
      pressure, area, and force were analyzed as a function of load, the specific
      tarsometatarsal joint, and foot position. RESULTS: The forces across these joints
      ranged from 2 to 541 N, but pressures ranged only from 0.5 to 5.7 MPa. In
      general, changes in load and foot position, in both the sagittal and the frontal
      plane, were associated with changes (p<0.05) in tarsometatarsal joint contact
      areas and forces. In contrast, the contact pressures across these joints varied
      minimally with changes in load and foot position. CONCLUSIONS: These data suggest
      that the tarsometatarsal joints are designed to regulate pressure in each joint
      by means of two mechanisms: (1) at small loads, an intrajoint mechanism regulates
      tarsometatarsal joint pressure by increasing contact area within the joint in
      response to increasing force, and (2) at larger loads, an interjoint mechanism
      engages to regulate tarsometatarsal joint pressure by redirecting force to other
      tarsometatarsal joints. CLINICAL RELEVANCE: The data provide both absolute
      (normal contact forces, areas, and pressures) and relative (intrajoint and
      interjoint regulating mechanisms) performance (functional) criteria for the
      development of new treatments for diseased or traumatized tarsometatarsal joints.

PMID- 11315781
TI  - Bone density adjacent to press-fit acetabular components. A prospective analysis
      with quantitative computed tomography.
AB  - BACKGROUND: The status of periprosthetic bone stock is an important concern when
      revision total hip arthroplasty is undertaken. Remodeling of periprosthetic
      femoral bone after total hip arthroplasty has been studied extensively, and the
      phenomenon of femoral stress-shielding has been well characterized. Finite
      element analysis and computer-simulated remodeling theory have predicted that
      retroacetabular bone-mineral density decreases after total hip arthroplasty;
      however, remodeling of periprosthetic pelvic bone in this setting has yet to be
      well defined. This study was conducted to evaluate the short-term natural history
      of periacetabular bone-mineral density following primary total hip arthroplasty.
      METHODS: Periacetabular bone-mineral density was studied prospectively in a group
      of twenty-six patients who underwent primary hybrid total hip arthroplasty for
      the treatment of advanced osteoarthritis. Density within the central part of the
      ilium (directly cephalad to a press-fit acetabular component) was assessed with
      serial quantitative computed tomography. Baseline density was measured within the
      first five days following the total hip arthroplasty. Ipsilateral density
      measurements were repeated at an average of 1.28 years postoperatively. Density
      values at corresponding levels of the contralateral ilium were obtained at both
      time-points in all patients to serve as internal controls. RESULTS: Bone-mineral
      density decreased significantly (p< or =0.001) between the two time-points on the
      side of the operation. The mean absolute magnitude of the interval density
      reduction (75 mg/cc) was greatest immediately adjacent to the implant (p<0.001),
      but it was also significantly reduced (by 35 mg/cc) at a distance of 10 mm
      cephalad to the implant (p = 0.001). Relative declines in mean density ranged
      from 33% to 20% of the baseline values. No focal bone resorption (osteolysis) was
      detected at the time of this short-term follow-up study. With the numbers
      available, no significant interval alteration in bone-mineral density was found
      on the untreated (internal control) side (p> or =0.07). CONCLUSIONS: We suggest
      that the observed decline in bone-mineral density represents a remodeling
      response to an altered stress pattern within the pelvis that was induced by the
      presence of the acetabular implant. This finding corroborates the predictions of
      finite element analysis and computer-simulated remodeling theory. It remains to
      be seen whether this trend of atrophy of retroacetabular bone stock will continue
      with longer follow-up or will ultimately affect the long-term stability of press
      fit acetabular components.

PMID- 11315782
TI  - Focal osteolysis at the junctions of a modular stainless-steel femoral
      intramedullary nail.
AB  - BACKGROUND: During routine follow-up of patients treated with a three-piece
      stainless-steel modular femoral nail, osteolysis and periosteal reaction around
      the modular junctions of some of the nails were noted on radiographs. The purpose
      of this study was to evaluate the prevalence, etiology, and clinical relevance of
      these radiographic findings. METHODS: Forty-four femoral fractures or nonunions
      in forty-two patients were treated with a modular stainless-steel femoral
      intramedullary nail. Seventeen nails were excluded, leaving twenty-seven
      intramedullary nails in twenty-seven patients for this study. All patients had
      had a femoral diaphyseal fracture; nineteen had had an acute fracture and eight,
      a nonunion. These twenty-seven patients returned for radiographs, a physical
      examination, assessment of functional outcomes, assessment of thigh pain with a
      visual analog scale, determination of serum chromium levels, and nail removal if
      desired. A control group of sixteen patients treated with a one-piece stainless
      steel femoral intramedullary nail was evaluated with use of the same outcome
      measures and was compared with the group treated with the modular femoral nail
      with regard to prevalence of thigh pain and serum chromium levels. Twelve modular
      femoral nails were removed according to the study protocol. The modular nail
      junctions were analyzed for corrosion products, and histopathologic analysis of
      tissue specimens from the femoral canal was performed. RESULTS: The twenty-seven
      patients were seen at a mean of twenty-one months after fracture fixation; twenty
      six of the twenty-seven fractures healed. Twenty-three femora had at least one of
      three types of abnormalities-osteolysis, periosteal reaction, or cortical
      thickening--localized to one or both modular junctions. Eighteen patients had
      severe reactions, defined as osteolysis of > or =2 mm, cortical thickening of >
      or =5 mm, and/or a periosteal reaction (group 1). Nine patients had mild or no
      reactions (group 2). Serum chromium levels in group 1 (mean, 1.27 ng/ mL; range,
      0.34 to 3.12 ng/mL) were twice as high as those in group 2 (mean, 0.53 ng/mL;
      range, 0.12 to 1.26 ng/mL). However, this difference did not reach significance
      with the numbers available. The differences in serum chromium levels between
      group 1 and the control group with a one-piece nail (mean, 0.26 ng/mL; range,
      0.015 to 1.25 ng/mL) (p<0.01) and a control group without an implant (mean, 0.05
      ng/mL; range, 0.015 to 0.25 ng/ mL) (p<0.01) were significant. The level of thigh
      pain recorded on the visual analog scale was also significantly different between
      group 1 and the control group with a one-piece implant (p = 0.03). Retrieved
      modular nails had signs of fretting corrosion as well as stainless-steel
      corrosion products adherent to the junction where the osteolysis occurred.
      Histologic and spectrographic analysis revealed two types of corrosion products
      that were consistent with stainless-steel within the peri-implant tissue and were
      associated with a foreign-body granulomatous response. CONCLUSIONS: The presence
      of corrosion products at the taper junctions suggests that particulate debris was
      a major factor in the etiology of the radiographic findings of osteolysis,
      periosteal reaction, and cortical thickening. Serum chromium levels were
      substantially elevated in the patients with a modular femoral nail, and such
      levels may serve as a marker of fretting corrosion of these devices.

PMID- 11315783
TI  - Selective restoration of motor function in the ulnar nerve by transfer of the
      anterior interosseous nerve. An anatomical feasibility study.
AB  - BACKGROUND: Proximal ulnar-nerve lesions have an unfavorable prognosis. The goal
      of the present study was to evaluate the feasibility of selective restoration of
      motor function of the ulnar nerve by the transfer of the anterior interosseous
      nerve or one of its branches to the motor branch of the ulnar nerve. METHODS: Ten
      cadaveric arms were used in the present study. The ulnar nerve and its motor and
      sensory branches as well as the anterior interosseous nerve and its branches were
      dissected. The widths of the motor branch of the ulnar nerve and the anterior
      interosseous nerve and its motor branches as well as the relevant distances from
      the points of divergence were measured. The axons were counted, and the distances
      from the end of the main anterior interosseous nerve, its motor branches, and the
      motor branch of the ulnar nerve to the level of the dorsal sensory branch of the
      ulnar nerve were measured. RESULTS: Our results indicate that the length, width,
      and number of axons of the branch of the anterior interosseous nerve to the
      pronator quadratus make it suitable for transfer to the motor branch of the ulnar
      nerve. The use of the main anterior interosseous nerve or its motor branches to
      the flexor pollicis longus and the flexor digitorum profundus is less feasible
      because of the need to graft a long segment and the longer distance from the
      level of transfer to the motor end points. CONCLUSIONS: The findings of the
      present study confirm the feasibility of motor-nerve transfer for reconstruction
      after an injury of the ulnar nerve. Nerve-grafting would be needed for injuries
      distal to the level of the dorsal sensory branch of the ulnar nerve.

PMID- 11315784
TI  - Dislodgment of polyethylene liners in first and second-generation Harris-Galante
      acetabular components. A report of eighteen cases.
AB  - BACKGROUND: Dislodgment of the polyethylene liner is an increasingly common
      complication following total hip arthroplasty. The purposes of this study are to
      present the results in a series of patients with this complication and to analyze
      the mode of failure. METHODS: Between November 1995 and January 2001, eighteen
      patients who had had a total hip arthroplasty presented with dislodgment of the
      polyethylene liner from a Harris-Galante metal acetabular shell. The medical
      records, radiographs, operative notes, and retrieved components were reviewed. In
      addition, scanning electron microscopy was used to study the fractured surfaces
      in a shell that had four broken tines. RESULTS: The components had been in situ
      for an average of seven years (range, three to eleven years). Seventeen
      components were second generation, and one was first generation. Symptoms
      developed spontaneously in sixteen patients, during sexual intercourse in one,
      and following a fall on the hip in one. Radiographs showed eccentric positioning
      of the head in all of the hips and broken tines in six. All of the shells were
      well fixed. Treatment consisted of revision of the shell in four patients,
      exchange of the liner in four, cementation of a new liner into the shell in
      seven, and cementation of an all-polyethylene cup in three. The liners had severe
      damage of the rim. Scanning-electron microscopy of the fractured surfaces of four
      tines revealed a fatigue pattern. CONCLUSIONS: We believe that, as the liner
      wears and becomes loose because of an inadequate locking mechanism, progressive
      micromotion occurs and the load increases on the polyethylene rim until it
      deforms and/or fractures. Subsequently, nothing prevents the liner from rotating
      out of the shell. As this mechanism of failure appears to include fatigue failure
      of the locking tines and wear of the liner, this complication is likely to
      increase as the components age in situ.

PMID- 11315785
TI  - Fungal infections of the spine. Report of eleven patients with long-term follow
      up.
AB  - BACKGROUND: Fungal infections of the spine are noncaseating, acid-fast-negative
      infections that occur primarily as opportunistic infections in immunocompromised
      patients. We analyzed eleven patients with spinal osteomyelitis caused by a
      fungus, and we developed suggestions for treatment. METHODS: All patients with a
      fungal infection of the spine treated by the authors over a sixteen-year period
      at three teaching institutions were evaluated. There was a total of eleven
      patients. Medical records and roentgenograms were available for every patient.
      Long-term follow-up of the nine surviving patients was performed by direct
      examination by the authors or by the patient's primary physician. RESULTS: For
      ten of the eleven patients, the average delay in the diagnosis was ninety-nine
      days. Nine patients were immunocompromised secondary to diabetes mellitus,
      corticosteroid use, chemotherapy for a tumor, or malnutrition. The sources of the
      spinal infections included direct implantation from trauma (one patient),
      hematogenous spread (four patients), and local extension (two patients). The
      infection followed elective spine surgery in three patients, and the cause was
      unknown in one. Paralysis secondary to the spine infection developed in eight
      patients. Ten patients were treated with surgical debridement. All eleven
      patients were treated with systemic antifungal medications for a minimum of six
      weeks. One patient died of generalized sepsis at thirty-three days, and another
      patient died of gastrointestinal hemorrhage at five months. After an average of
      6.3 years of follow-up, the infection had resolved in all nine surviving
      patients. CONCLUSIONS: Treatment of fungal spondylitis is often delayed because
      of difficulty with the diagnosis. Delay in the diagnosis led to poorer results in
      terms of neurologic recovery in our study. Performing fungal cultures whenever a
      spinal infection is suspected might hasten the diagnosis. Patients should be
      given a guarded prognosis and informed of the many possible complications of the
      disease.

PMID- 11315786
TI  - Quantification of laser-induced cartilage injury by confocal microscopy in an ex
      vivo model.
AB  - BACKGROUND: The application of lasers in orthopaedic surgery is increasing.
      However, some investigators have reported that osteonecrosis may occur after
      laser meniscectomy. The objective of the present study was to evaluate the effect
      of laser wavelength and energy on cartilage injury in an ex vivo model. METHODS:
      Fresh bovine articular cartilage was exposed to either holmium:yttrium-aluminum
      garnet (Ho:YAG) or erbium:YAG-laser (Er:YAG) irradiation. Both lasers were
      operated in a free-running mode and at a pulse-repetition rate of 8 Hz. The
      effect of laser treatment at several energy levels (Er:YAG at 100 and 150 mJ and
      Ho:YAG at 500 and 800 mJ) was examined. For each light source and energy level,
      ten cartilage samples were assessed by conventional histological analysis and by
      confocal microscopy. Thermal damage was assessed by determining cell viability.
      RESULTS: The extent of thermal damage demonstrated by confocal microscopy was
      much greater than that demonstrated by histological analysis. The extent of
      thermal injury after Ho:YAG-laser irradiation was much greater than that after
      Er:YAG-laser irradiation, which was associated with almost no damage. In
      addition, the ablation depth was greater after treatment with the Er:YAG laser
      than after treatment with the Ho:YAG laser. CONCLUSIONS: In the present study,
      histological analysis underestimated thermal damage after laser irradiation. In
      addition, our findings highlighted problems associated with use of high-power
      settings of Ho:YAG lasers during arthroscopic surgery.

PMID- 11315787
TI  - A randomized trial of controlled-release oxycodone during inpatient
      rehabilitation following unilateral total knee arthroplasty.
AB  - BACKGROUND: Reliance on "as-needed" analgesia following total knee arthroplasty
      may lead to inadequate control of pain and delayed recovery of function.
      Preemptive use of controlled-release opioids may improve pain control, accelerate
      recovery, and reduce the need for inpatient rehabilitative services. This study
      was designed to determine whether controlled-release opioids enhance post
      arthroplasty pain control and facilitate functional recovery during
      rehabilitation. METHODS: Fifty-nine patients admitted for inpatient
      rehabilitation following unilateral total knee arthroplasty were randomized to
      receive OxyContin (controlled-release oxycodone) (twenty-nine patients) or a
      placebo (thirty patients) every twelve hours. Both groups could receive on
      request, immediate-release oxycodone (5 mg every four hours). The dose of study
      medication was increased on the basis of the frequency of requests for immediate
      release oxycodone. Measures of interest included pain ratings as determined with
      a visual-analog scale, changes in the range of motion of the knee and quadriceps
      strength, and improvements in selected Functional Independence Measure scores
      during the first eight physical therapy sessions. The duration of the hospital
      stay for rehabilitation also was compared between the two groups. RESULTS:
      Baseline demographic, clinical, and functional characteristics were similar
      between the OxyContin and placebo groups. Compared with the placebo group, the
      patients who received OxyContin reported significantly less pain as well as
      significantly greater range of motion of the knee (passive motion, p = 0.036;
      active motion, p< 0.001) and quadriceps strength (p = 0.001) by the eighth
      physical therapy session. The patients who received OxyContin also were
      discharged from the rehabilitation hospital at an average of 2.3 days earlier
      than the patients in the placebo group (p = 0.013). CONCLUSIONS: Preemptive use
      of controlled-release oxycodone during rehabilitation following total knee
      arthroplasty leads to improved pain control, more rapid functional recovery, and
      a reduced need for inpatient rehabilitative services.

PMID- 11315788
TI  - Clinical value of routine preoperative magnetic resonance imaging in adolescent
      idiopathic scoliosis. A prospective study of three hundred and twenty-seven
      patients.
AB  - BACKGROUND: The prevalence of intraspinal pathology associated with scoliosis has
      been reported to be as high as 26% in some series, and, on the basis of this
      finding, preoperative magnetic resonance imaging is used in the screening of
      patients with adolescent idiopathic scoliosis. However, this practice continues
      to be highly controversial. In order to better resolve this issue, we performed
      what we believe to be the largest prospective study to evaluate the need for
      preoperative magnetic resonance imaging in patients with adolescent idiopathic
      scoliosis requiring arthrodesis of the spine. METHODS: A total of 327 consecutive
      patients with adolescent idiopathic scoliosis were evaluated between December
      1991 and March 1999. All patients in the study presented with an adolescent
      idiopathic scoliosis curve pattern and had a complete physical and neurologic
      examination. Magnetic resonance imaging of the brain and the spinal cord were
      performed as part of their preoperative work-up. RESULTS: Seven patients had an
      abnormality noted on magnetic resonance imaging. These abnormalities included a
      spinal cord syrinx in two patients (0.6%) and an Arnold-Chiari type-I
      malformation in four (1.2%). One patient had an abnormal fatty infiltration of
      the tenth thoracic vertebral body. No patient required neurosurgical intervention
      or additional work-up. All patients who underwent spinal arthrodesis with
      segmental instrumentation tolerated the surgery without any immediate or delayed
      neurologic sequelae. CONCLUSIONS: The fact that magnetic resonance imaging did
      not detect any important pathology in the large number of patients in this study
      strongly suggests that magnetic resonance imaging is not indicated prior to
      arthrodesis of the spine in patients with an adolescent idiopathic scoliosis
      curve pattern and a normal physical and neurologic examination.

PMID- 11315789
TI  - Thorn-induced pseudotumor of the metatarsal. A case report.

PMID- 11315790
TI  - Calcifying aponeurotic fibroma of the hand. A case report.

PMID- 11315791
TI  - Acute sciatic and femoral neuritis following total hip arthroplasty. A case
      report.

PMID- 11315792
TI  - Shoulder arthrodesis.
AB  - Current indications for shoulder arthrodesis include posttraumatic brachial
      plexus injuries, paralysis of the deltoid muscle and rotator cuff, chronic
      infection, failed revision arthroplasty, severe refractory instability, and bone
      deficiency following resection of a tumor in the proximal aspect of the humerus.
      The trapezius, levator scapulae, serratus anterior, and rhomboid muscles must be
      functional to optimize the functional result following shoulder arthrodesis. A
      consensus has not been reached concerning the ideal position of the shoulder
      arthrodesis, although excessive abduction or flexion has been associated with
      chronic postoperative pain. Decortication of both the acromiohumeral and the
      glenohumeral surfaces to increase the surface area available for arthrodesis is
      the most common means for obtaining successful fusion. Although there are
      numerous methods for stabilization of a shoulder arthrodesis, the most popular
      method today is probably the AO technique with either a single plate or double
      plates.

PMID- 11315793
TI  - E-mail in clinical orthopaedic practice.

PMID- 11315794
TI  - Accessing orthopaedic information on the internet.

PMID- 11315795
TI  - Short-term outcomes analysis in pediatric orthopaedics.

PMID- 11315796
TI  - The fallacy of short-term outcome analysis in pediatric orthopaedics.

PMID- 11315797
TI  - Neviaser's contribution to the treatment of ALPSA lesions.

PMID- 11315798
TI  - Data in clinical studies of volumetric wear rates.

PMID- 11315799
TI  - A legal perspective of surrogacy and paternalism.

PMID- 11315800
TI  - Local recurrence of chondroblastoma.

PMID- 11315801
TI  - Range of motion and dominance in the upper extremity.

PMID- 11315802
TI  - Teaching professionalism in orthopaedic residency.
AB  - Two residents, wearing white coats with their names and "Department of
      Orthopaedics" conspicuously embroidered on them, boarded a hospital elevator
      crowded with physicians, employees, and visitors. In a clearly audible voice, one
      resident began a story: "You should have seen the patient I saw in my clinic the
      other day. She was beautiful. I should send her to see Dr. W. He would love to
      see her!" This comment drew the undivided attention of everyone in the elevator
      and cast a ghastly silence over the rest of the ride. In recent years, interest
      has expanded regarding professionalism and its importance in medicine and
      surgery. Orthopaedic surgery is no exception, as the topic has recently reached
      prominence in our literature and policies. It is unlikely that professionalism is
      a universal and innate characteristic of college students entering medical
      school, yet it becomes a necessary value in medical practice. Somewhere in the
      ongoing process of medical education, the issue must be addressed.

PMID- 11315803
TI  - What's new in musculoskeletal tumor surgery.

PMID- 11315804
TI  - Scale up of fuel ethanol production from sugar beet juice using loofa sponge
      immobilized bioreactor.
AB  - Production of fuel ethanol from sugar beet juice, using cells immobilized on
      loofa sponge was investigated. Based on ethanol productivity and ease of cell
      immobilization, a flocculating yeast strain, Saccharomyces cerevisiae IR2 was
      selected for ethanol production from sugar beet juice. It was found that raw
      sugar beet juice was an optimal substrate for ethanol production, requiring
      neither pH adjustment nor nitrogen source supplement. When compared with a 2 l
      bubble column bioreactor, mixing was not sufficient in an 8 l bioreactor
      containing a bed of sliced loofa sponges and consequently, the immobilized cells
      were not uniformly distributed within the bed. Most of the cells were immobilized
      in the lower part of the bed and this resulted in decreased ethanol productivity.
      By using an external loop bioreactor, constructing the fixed bed with cylindrical
      loofa sponges, dividing the bed into upper, middle and lower sections with
      approximately 1 cm spaces between them and circulating the broth through the loop
      during the immobilization, uniform cell distribution within the bed was achieved.
      Using this method, the system was scaled up to 50 l and when compared with the 2
      l bubble column bioreactor, there were no significant differences (P > 0.05) in
      ethanol productivity and yield. By using external loop bioreactor to immobilize
      the cells uniformly on the loofa sponge beds, efficient large scale ethanol
      production systems can be constructed.

PMID- 11315805
TI  - Effect of pyrolysis temperature on composition, surface properties and thermal
      degradation rates of Brazil Nut shells.
AB  - Changes in chemical and surface characteristics of Brazil Nut shells
      (Bertholletia excelsa) due to pyrolysis at different temperatures (350 degrees C,
      600 degrees C, 850 degrees C) were examined. For this purpose, proximate and
      ultimate analyses, physical adsorption measurements of N2 (-196 degrees C) and
      CO, (25 degrees C) as well as samples visualisation by scanning electronic
      microscopy (SEM) were performed. Appreciable differences in the residue
      characteristics, depending markedly on the pyrolysis temperature, were observed.
      Release of volatile matter led to the development of pores of different sizes.
      Progressive increases in micropore development with increasing pyrolysis
      temperature took place, whereas a maximum development of larger pores occurred at
      600 degrees C. Furthermore, kinetics measurements of Brazil Nut shells pyrolysis
      from ambient temperature up to 900 degrees C were performed by non-isothermal
      thermogravimetric analysis. A model taking into account the significant changes
      in the residue during pyrolysis, through an increase in the activation energy
      with temperature and solid conversion, were found to properly fit the kinetics
      data over the wide range of degradation investigated.

PMID- 11315806
TI  - Effect of culture conditions on lipase production by Fusarium solani in batch
      fermentation.
AB  - Lipase (Glycerol ester hydrolase EC 3.1.1.3.) from a Brazilian strain of Fusarium
      solani FSI has been investigated. The effect of different carbon sources and
      trace elements added to basal medium was observed with the aim of improving
      enzyme production. Lipase specific activity was highest (0.45 U mg(-1)) for
      sesame oil. When this medium was supplemented with trace elements using olive
      oil, corn oil and sesame oil the lipase specific activity increased to 0.86, 1.89
      and 1.64 U mg(-1), respectively, after 96 h cultivation without any considerable
      biomass increase. The Km of this lipase using pNPP (p-nitrophenylpalmitate) as
      substrate, was 1.8 mM with a Vmax of 1.7 micromol min(-1) mg protein(-1). Lipase
      activity increased in the presence of increasing concentrations of hexane and
      toluene. In contrast, incubation of this enzyme with water-soluble solvents
      decreased its activity after 10% concentration (v/v) of the solvent. The lipase
      activity was stable below 35 degrees C but above this temperature activity losses
      were observed.

PMID- 11315807
TI  - Complexes of arabinogalactan of Pereskia aculeata and Co2+, Cu2+, Mn2+, and Ni2+.
AB  - The main interest in the biopolymer arabinogalactan is that it is edible.
      Complementing its high protein percentage, when complexed to essential metal
      ions, widens the use in food and pharmacology industries and technologies. The
      binding constants of Co2+, Cu2+, Mn2+ and Ni2+ with arabinogalactan, extracted
      from the leaves of Pereskia aculeata from Brazil were determined by
      potentiometric titrations and also the speciation according to pH values. The
      complexed species proposed by potentiometric titrations and the unique complexing
      ability of galacturonic acid groups towards Cu2+ and Ni2+ in the tridimensional
      web structure of arabinogalactan were confirmed by IR and EPR spectroscopies. The
      thermal stability of the complexed species also varied with the metal ion
      employed in the complexation when compared to the biopolymer alone. These
      complexes are new sources of additives for the food and pharmacology industries
      and carriers of essential metal ions to animal and vegetal biochemistry.

PMID- 11315808
TI  - Agronomic use of biotechnologically processed grape wastes.
AB  - Grape waste was composted by biodegradation and subsequently used as an organic
      fertilizer for 20 day-corn. Combinations of recently compressed grape waste and
      hen droppings (10% w/w) were prepared to study the activating effect of hen
      droppings and the effect of aeration on the composting process. The final
      hydrogen potential (pH), %C, %N and C/N ratio, indicated an adequate development
      of the bioprocess. Satisfactory results were observed when the products were
      applied at several doses (1,000-4,000 kg/ ha) as a soil conditioner for corn seed
      germination in greenhouses. Only the addition of hen droppings had a significant
      effect (P < 0.05) on corn dry matter (14% increase). A dose of 3000 kg/ha was
      considered as optimal and was used supplemented with triple superphosphate (TSP)
      in agronomic trials. All the treatments produced greater corn dry matter (P <
      0.05) than the chemical industrial fertilizer used as a control (0.52-0.71 g/pot
      for the organic fertilizers vs 0.45 g/pot for the control). Anaerobic conditions
      and hen droppings addition significantly produced (P < 0.05) higher corn dry
      matter.

PMID- 11315809
TI  - Performance evaluation of a mesophilic anaerobic fluidized-bed reactor treating
      wastewater derived from the production of proteins from extracted sunflower
      flour.
AB  - A study of the anaerobic digestion of wastewater derived from the production of
      protein isolates from extracted sunflower flour was carried out in a laboratory
      scale, mesophilic (35 degrees C) fluidized-bed reactor with saponite as bacterial
      support. Chemical oxygen demand (COD) removal efficiencies in the range of 98.3
      80.0% were achieved in the reactor at organic loading rates (OLR) of between 0.6
      and 9.3 g COD/I d, hydraulic retention times (HRT) of between 20.0 and 1.1 d and
      average feed COD concentration of 10.6 g/l. Eighty percent of feed COD could be
      removed up to OLR of 9.3 g COD/l d. The yield coefficient of methane production
      was 0.33 l of methane (at STP) per gram of COD removed and was virtually
      independent of the OLR applied. Because the buffering capacity of the
      experimental system was maintained at favorable levels with excess total
      alkalinity present at all loadings, the rate of methanogenesis was not affected
      by loading. The experimental data indicated that a total alkalinity in the range
      of 2,000-2,460 mg/l as CaCO3 was sufficient to prevent the pH from dropping to
      below 7.0 for OLR of up to 9.3 g COD/l d. The volatile fatty acid (VFA) levels
      and the VFA/alkalinity ratio were lower than the suggested limits for digester
      failure (0.3-0.4) for OLR and HRT up to 9.3 g COD/l d and 1.1 d, respectively.
      For a HRT of 0.87 d (OLR of 12.1 g COD/l d) the start of acidification was
      observed in the reactor.

PMID- 11315810
TI  - Production of beta-carotene by a Rhodotorula glutinis mutant in sea water medium.
AB  - Mutant 32, derived from Rhodotorula glutinis NCIM 3353 produced 76-fold more beta
      carotene than the parent strain. In the growth medium prepared in seawater, the
      total carotenoid content and dry cell mass was 86 mg/l and 16 g/l, respectively,
      as compared to 70 mg/l and 12 g/l obtained with a medium prepared in distilled
      water. A 2-fold increase in beta-carotene with simultaneous 2.3-fold decrease in
      torulene content was also observed. When grown in seawater medium at pH 6.0, 83
      +/- 5% carotenoids could be extracted from the cells without any mechanical
      disintegration.

PMID- 11315811
TI  - Laboratory composting of extruded poly(lactic acid) sheets.
AB  - Composting of extruded poly(lactic acid) (PLA) in combination with pre-composted
      yard waste in a laboratory composting system was studied. Yard waste and PLA
      mixtures containing 0%, 10%, or 30% PLA (dry weight basis) were placed in
      composting vessels for four weeks. Exhaust gases were analyzed for carbon dioxide
      concentration twice per week. After the first week, significantly greater (P <
      0.05) amounts of carbon dioxide were generated in vessels with 10% or 30% PLA
      than in control (0% PLA) vessels. Data indicated that microbial degradation of
      PLA occurred. There was no significant difference (P > 0.05) in carbon dioxide
      emission between 10% and 30% PLA mixtures. Compost pH dropped (from 6.0 to 4.0)
      after 4 weeks of composting for 30% PLA, but remained unchanged (6.3) for 0% or
      10% PLA. Most likely, in the case of 30% PLA, substantial chemical hydrolysis and
      lactic acid generation lowered the compost pH. The lowered pH likely suppressed
      microbial activity, thus explaining the lack of difference in carbon dioxide
      emissions between 10% and 30% PLA mixtures. Gel permeation chromatography showed
      a notable decrease in PLA molecular weight as a result of composting. It was
      demonstrated that PLA can be efficiently composted when added in small amounts
      (<30% by weight) to pre-composted yard waste.

PMID- 11315812
TI  - Removal of heavy metals from industrial wastewaters by adsorption onto activated
      carbon prepared from an agricultural solid waste.
AB  - Activated carbon was prepared from coirpith by a chemical activation method and
      characterized. The adsorption of toxic heavy metals, Hg(II), Pb(II), Cd(II),
      Ni(II), and Cu(II) was studied using synthetic solutions and was reported
      elsewhere. In the present work the adsorption of toxic heavy metals from
      industrial wastewaters onto coirpith carbon was studied. The percent adsorption
      increased with increase in pH from 2 to 6 and remained constant up to 10. As
      coirpith is discarded as waste from coir processing industries, the resulting
      carbon is expected to be an economical product for the removal of toxic heavy
      metals from industrial wastewaters.

PMID- 11315813
TI  - Biosorption of cadmium(II), lead (II) and copper(II) with the filamentous fungus
      Phanerochaete chrysosporium.
AB  - The biosorption from artificial wastewaters of heavy metals (Cd(II), Pb(II) and
      Cu(II)) onto the dry fungal biomass of Phanerochaete chryosporium was studied in
      the concentration range of 5-500 mg l(-1). The maximum absorption of different
      heavy metal ions on the fungal biomass was obtained at pH 6.0 and the biosorption
      equilibrium was established after about 6 h. The experimental biosorption data
      for Cd(II), Pb(II) and Cu(II) ions were in good agreement with those calculated
      by the Langmuir model.

PMID- 11315814
TI  - Slow-release effect of N-functionalized kraft lignin tested with Sorghum over two
      growth periods.
AB  - Biomass production of fodder sorghum (Sorghum sp.) has been tested in a field
      trial over two harvesting periods under natural meteorological conditions using
      ammoxidized kraft lignin (AKL) as a slow-release fertilizer and urea as
      conventional reference. In the course of the first growth cycle, plants treated
      with urea gave higher biomass yields because of the better solubility of urea in
      the initial phase. However, during the second cycle AKL treated plants performed
      better than urea treated sorghum, indicating that nitrogen from AKL became
      readily available.

PMID- 11315815
TI  - Hyperaccumulation of cadmium by roots, bulbs and shoots of garlic (Allium sativum
      L.).
AB  - The effects of cadmium chloride concentration on root, bulb and shoot growth of
      garlic (Allium sativum L.), and the uptake and accumulation of Cd2+ by garlic
      roots, bulbs and shoots were investigated. The range of cadmium chloride (CdCl2 x
      2.5H2O) concentrations was 10(-6) - 10(-2) M. Cadmium stimulated root length at
      lower concentrations (10(-6) - 10(-5) M) significantly (P < 0.005) during the
      entire treatment period. The seedlings exposed to 10(-3) - 10(-2) M Cd exhibited
      substantial growth reduction (P < 0.005), but did not develop chlorosis. Garlic
      has considerable ability to remove Cd from solutions and accumulate it. The Cd
      content in roots of garlic increased with increasing solution concentration of
      Cd2+. The roots in plants exposed to 10(-2) M Cd accumulated a large amount of
      Cd. approximately 1,826 times the control. The Cd contents in roots of plants
      treated with 10(-3), 10(-4), 10(-5) and 10(-6) M Cd were approximately 114, 59,
      24 and 4 times the control, respectively. However, the plants transported only a
      small amount of Cd to their bulbs and shoots and concentrations in these tissues
      were low.

PMID- 11315816
TI  - Low-fat diets for diabetes prevention.

PMID- 11315817
TI  - Friends of the oppressed foot?

PMID- 11315818
TI  - The National Diabetes Education Program, changing the way diabetes is treated:
      comprehensive diabetes care.

PMID- 11315819
TI  - Long-term (5-year) effects of a reduced-fat diet intervention in individuals with
      glucose intolerance.
AB  - OBJECTIVE: To determine whether reducing dietary fat would reduce body weight and
      improve long-term glycemia in people with glucose intolerance. RESEARCH DESIGN
      AND METHODS: A 5-year Follow-up of a 1-year randomized controlled trial of a
      reduced-fat ad libitum diet versus a usual diet. Participants with glucose
      intolerance (2-h blood glucose 7.0-11.0 mmol/l) were recruited from a Workforce
      Diabetes Survey. The group that was randomized to a reduced-fat diet participated
      in monthly small-group education sessions on reduced-fat eating for 1 year. Body
      weight and glucose tolerance were measured in 136 participants at baseline 6
      months, and 1 year (end of intervention), with follow-up at 2 years (n = l04), 3
      years (n = 99), and 5 years (n = 103). RESULTS: Compared with the control group,
      weight decreased in the reduced-fat-diet group (P < 0.0001); the greatest
      difference was noted at 1 year (-3.3 kg), diminished at subsequent follow-up (
      3.2 kg at 2 years and -1.6 kg at 3 years), and was no longer present by 5 years
      (1.1 kg). Glucose tolerance also improved in patients on the reduced-fat diet; a
      lower proportion had type 2 diabetes or impaired glucose tolerance at 1 year (47
      vs. 67%, P < 0.05), but in subsequent years, there were no differences between
      groups. However, the more compliant 50% of the intervention group maintained
      lower fasting and 2-h glucose at 5 years (P = 0.041 and P = 0.026 respectively)
      compared with control subjects. CONCLUSIONS: The natural history for people at
      high risk of developing type 2 diabetes is weight gain and deterioration in
      glucose tolerance. This process may be ameliorated through adherence to a reduced
      fat intake

PMID- 11315820
TI  - Guidelines for premeal insulin dose reduction for postprandial exercise of
      different intensities and durations in type 1 diabetic subjects treated
      intensively with a basal-bolus insulin regimen (ultralente-lispro).
AB  - OBJECTIVE: To evaluate and validate appropriate premeal insulin dose reductions
      for postprandial exercises of different intensities and durations to minimize the
      risk of exercise-induced hypoglycemia in type 1 diabetic subjects. RESEARCH
      DESIGN AND METHODS: Eight male type 1 diabetic patients on a basal-bolus insulin
      regimen of ultralente (UL) as basal insulin and lispro (LP) as premeal insulin
      were tested in a randomized, crossover fashion during postprandial exercise at
      25% VO2max for 60 min, 50% VO2max for 30 and 60 min, and 75% VOmax for 30 min
      starting 90 min after a standardized mixed breakfast (600 kcal, 75 g
      carbohydrates). Each subject served as his own control and was rested after a
      full dose of insulin LP (LP 100%) and/or 50% (LP 50%) and/or 25% (LP 25%) of the
      current dose. RESULTS: At all intensities, the full premeal insulin dose was
      associated with an increased risk of hypoglycemia. At 25% VO2max for 60 min, a
      50% reduction in the premeal insulin dose resulted in plasma glucose of -0.62
      mmol/l compared with baseline at the end of exercise. At 50% VO2max for 30 and 60
      min, 50 and 75% reductions of the premeal insulin dose were associated with
      plasma glucose of -0.39 and +0.49 mmol/l, respectively, at the end of the
      exercise. At 75% VO2max, a 75% reduction of the premeal insulin dose was required
      to achieve appropriate postexercise plasma glucose (+0.71 mmol/l). Such
      reductions in the premeal insulin dose resulted in a 75% decrease in the
      incidence of exercise-induced hypoglycemia. CONCLUSIONS In well-controlled type 1
      diabetic subjects on intensive insulin therapy with the basal-bolus (UL-LP)
      insulin regimen, risk of hypoglycemia can be minimized during postprandial
      exercises of different intensities and different durations by appropriate
      reduction of premeal insulin LP.

PMID- 11315821
TI  - Basal insulin therapy in type 2 diabetes: 28-week comparison of insulin glargine
      (HOE 901) and NPH insulin.
AB  - OBJECTIVE: To determine the safety and efficacy of the long-acting analog insulin
      glargine compared with NPH insulin in patients with type 2 diabetes who were
      previously treated with insulin alone. RESEARCH DESIGN AND METHODS: A total of
      518 subjects with type 2 diabetes who were receiving NPH insulin with or without
      regular insulin for postprandial control were randomized to receive insulin
      glargine (HOE 901) once daily (n = 259) or NPH insulin once or twice daily in =
      259) for 28 weeks in an open-label, multicenter trial. Doses were adjusted to
      obtain target fasting glucose <6.7 mmol/l. At study end point, the median total
      daily insulin dose in both treatment groups was 0.75 IU/kg. RESULTS: The
      treatment groups showed similar improvements in HbA1c from baseline to end point
      on intent-to-treat analysis. The mean change (means +/- SD) in HbA1c from
      baseline to end point was similar in the insulin glargine group (-0.41 +/- 0.1%)
      and the NPH group (-0.59 +/- 0.1%) after patients began with an average baseline
      HbA1c of approximately 8.5%. The treatments were associated with similar
      reductions in fasting glucose levels. Overall, mild symptomatic hypoglycemia was
      similar in insulin glargine subjects (61.4%) and NPH insulin subjects (66.%)
      However, nocturnal hypoglycemia in the insulin glargine group was reduced by 25%
      during the treatment period after the dose-titration phase(26.5 vs. 35.5%, P =
      0.0136). Subjects in the insulin glargine group experienced less weight gain than
      those in the NPH group (0.4 vs. 1.4 kg, P < 0.0007). CONCLUSIONS: In patients
      with type 2 diabetes, once-daily bedtime insulin glargine is as effective as once
      or twice-daily NPH in improving and maintaining glycemic control. In addition,
      insulin glargine deonstrates a lower risk of nocturnal hypoglycemia and less
      weight gain compared with NPH insulin.

PMID- 11315822
TI  - Blood glucose awareness training (BGAT-2): long-term benefits.
AB  - OBJECTIVE: Blood glucose awareness training (BGAT) has been shown to improve
      awareness of blood glucose (BG) fluctuations among adults with type 1 diabetes.
      This study investigates the long-term (12-month) benefits of BGAT-2. RESEARCH
      DESIGN AND METHODS: A total of 73 adults with type 1 diabetes participated in a 6
      month repeated baseline design with a 12-month follow-up. At 6 months and 1 month
      before BGAT-2 and at 1,6, and 12 months after BGAT-2, subjects used a handheld
      computer for 50 trials and completed psychological tests. Throughout assessment,
      subjects completed diaries, recording occurrences of diabetic ketoacidosis,
      severe hypoglycemia, and motor vehicle violations During follow-up, 50% of the
      subjects received booster training. RESULTS: During the first and last halves of
      both the baseline period and the follow-up period, dependent variables were
      generally stable. However, from baseline to follow-up, BGAT-2 led to 1) improved
      detection of hypoglycemia and hyperglycemia; 2) improved judgment regarding when
      to lower high BG, raise low BG, and not drive while hypoglycemic; 3) reduction in
      occurrence of diabetic ketoacidosis, severe hypoglycemia, and motor vehicle
      violations; and 4) improvement in terms of worry about hypoglycemia, quality of
      life, and diabetes knowledge. Reduction in severe hypoglycemia was not associated
      with a worsening of metabolic control (HbA1). The presence or absence of booster
      training did not differentially affect these benefits. CONCLUSION: BGAT has
      sustained broad-ranging benefits, independent of booster intervention.

PMID- 11315823
TI  - Mini-dose glucagon rescue for hypoglycemia in children with type 1 diabetes.
AB  - OBJECTIVE: Children with type 1 diabetes are frequently difficult to manage
      during times of gastroenteritis or poor oral intake of carbohydrates because of
      mild or impending hypoglycemia. The present study describes the effective use of
      small doses of subcutaneous glucagon in these children. RESEARCH DESIGN AND
      METHODS: We analyzed 33 episodes of impending or mild hypoglycemia in 28 children
      (ages 6.6 +/- 0.7 years). All were healthy except for type 1 diabetes and an
      episode of gastroenteritis. Using a standard U-100 insulin syringe, children ages
      < or = 2 years received two "units" (20 microg) of glucagon subcutaneously and
      those ages >2 years received one unit/year of age up to 15 units (150 microg). If
      the blood glucose did not increase within 30 min, the initial dosage was doubled
      and given at that time. We used patients' self-glucose monitoring devices,
      aqueous glucagon, standard insulin syringes, and frequent phone contact with a
      physician and/or a diabetes nurse educator in this study. RESULTS: Blood glucose
      was 3.44 +/- 0.15 mmol/l before and 8.11 +/- 0.72 mmol/l 30 min after glucagon.
      In 14 children, relative hypoglycemia recurred, requiring retreatment (3.48 +/-
      0.18 to 6.94 +/- 0.72 mmol/l). In four children, a third dose was required. The
      glucagon was well tolerated In 28 of the 33 episodes of impending hypoglycemia,
      the children remained at home and fully recovered. Five children were taken to
      their local hospital because of concerns of dehydration or fever, but none for
      hypoglycemia. CONCLUSIONS: Mini-dose glucagon rescue, using subcutaneous
      injections, is effective in managing children with type 1 diabetes during
      episodes of impending hypoglycemia due to gastroenteritis or poor oral intake of
      carbohydrate.

PMID- 11315824
TI  - Factors predicting the age when type 2 diabetes is diagnosed in Hong Kong Chinese
      subjects.
AB  - OBJECTIVE: To examine the factors predicting age at diagnosis of type 2 diabetes
      in Hong Kong Chinese. RESEARCH DESIGN AND METHODS: The relationships between age
      at diagnosis and parental history of diabetes as well as an array of clinical and
      metabolic factors were examined using a hospital clinic-based diabetes registry
      involving 3,414 index patients with type 2 diabetes Patterns of age at diagnosis
      in successive generations were also examined using 21 affected child-parent pairs
      and 7 affected child-parent-grandparent trios. RESULTS: Approximately 29% of the
      index patients were diagnosed with type 2 diabetes at < or = 35 years of age
      (hereby defined as early-onset). Compared with the patients diagnosed at >35
      years of age (hereby defined as late-onset) the early-onset patients had higher
      rates of positive paternal (16 vs. 5%) and maternal (22 vs. 12%) history of
      diabetes (both at P < 0.01) and had poorer metabolic profiles. In the overall
      index patients, male sex, higher HbA1c waist-to-hip ratio (WHR), and systolic
      blood pressure (sBP); lower HDL cholesterol level; and a positive paternal was
      well as maternal history of diabetes predicted younger age at diagnosis. More
      senior age and higher BMI and diastolic blood pressure predicted olderq age at
      diagnosis. Predictors for younger age at diagnosis in the male patients were
      higher HbA1c and sBP and a positive paternal history of diabetes Predictors for
      younger age at diagnosis in the female patients were higher HbA1c WHR, and sBP
      and a paternal as well as maternal history of diabetes. In the affected child
      parent pairs and clild-parent-grandparent trios there was a decrease in age at
      diagnosis in successive generations. CONCLUSIONS: Our data indicate that both
      familial (possibly genetic) and metabolic factors affect the age of onset of type
      2 diabetes in the Chinese population. The results also suggest an onset and
      progression pattern of the disease that is compatible with the phenomenon of
      anticipation.

PMID- 11315825
TI  - Type 1 diabetes environmental factors and correspondence analysis of HLA class II
      genes in the Yemenite Jewish community in Israel.
AB  - OBJECTIVE: The Israeli Yemenite Jewish community has displayed an exceptionally
      rapid increase in the frequency of type 1 diabetes, having the highest rate of
      all Israeli ethnic groups. We studied the role of the environment, in relation to
      the nature and frequency of HLA class II genes, to evaluate its possible
      involvement in the development of diabetes. RESEARCH DESIGN AND METHODS: We
      interviewed 196 elderly Yemenite women, who had immigrated to Israel as adults,
      in programmed encounters about signs and symptoms of type 1 diabetes, infant
      feeding customs, and infectious diseases in Yemen. We also performed HLA
      oligotyping of DRB1, DQA1, and DQB1 genes in 120 unrelated Yemenite Jews,
      including 44 type 1 diabetic patients and 76 healthy control subjects, and used
      these data in correspondence analysis comparing Yemenites with different Israeli
      ethnic groups. RESULTS: Interviews indicated that early exposure to cow's milk
      was very common in Yemen. However, none of the women could recall classical
      presentations of diabetes. HLA oligotyping showed that gene frequencies of non
      Asp-57 (of the HLA-DQB chain) in the patients (0.94) and control subjects (0.6)
      were similar to those of other populations with a known high incidence of type 1
      diabetes. Correspondence analysis revealed that Yemenite Jews are genetically
      distinct from other ethnic groups in Israel. CONCLUSIONS: The genetic
      distinctiveness of Yemenite Jews may explain their unusually high incidence of
      type 1 diabetes in Israel. Despite the presence of highly susceptible
      diabetogenic HL4 class II genes in this community, early exposure to cow's milk
      did not cause phenotypic expression of diabetes in Yemen. This finding suggests
      that in this population, either cow's milk does not play a crucial role in
      triggering diabetes, or environmentally conferred protection, such as frequent
      infectious disease in Yemen, was dominant.

PMID- 11315826
TI  - Baseline characteristics of the diabetic participants in the Antihypertensive and
      Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).
AB  - OBJECTIVE: Hypertension (HTN) is a major risk factor for cardiovascular disease
      (CVD) in the setting of diabetes. There is no consensus on how best to treat
      hypertension among those with diabetes. Here we describe the characteristics of a
      cohort of hypertensive adults with diabetes who are part of a large prospective
      blood pressure study. This study will help clarify the treatment of HTN in the
      setting of diabetes. RESEARCH DESIGN AND METHODS: The Antihypertensive and Lipid
      Lowering high-risk hypertensive participants, ages > or = 55 years, designed to
      determine whether the incidence of fatal and nonfatal coronary heart disease
      (CHD) and combined cardiovascular events (fatal and nonfatal CHD,
      revascularization surgery, angina pectoris, congestive heart failure, and stroke)
      differs between diuretic (chlorthalidone) treatment and three alternative
      antihypertensive therapies: a calcium channel blocker (amlodipine), an ACE
      inhibitor (lisinopril), and an alpha-adrenergic blocker (doxazosin). The planned
      follow-up is an average of 6 years, to be completed March 2002. RESULTS: There
      are 15,297 diabetic individuals in the ALLHAT study (36.0% of the entire cohort).
      Of these individuals, 50.2% are male, 39.4% are African-American, and 17.7% are
      Hispanic. Demographic and laboratory characteristics of the cohort are similar to
      those of other studies of the U.S. elderly population with HTN. The sample size
      has 42 and 93% confidence, treatments for the two study outcomes. CONCLUSIONS:
      The diabetic cohort in ALLHAT wil be able to provide valuable information about
      the treatment of hypertension in older diabetic patients at risk for incident
      CVD.

PMID- 11315827
TI  - Rates and risk factors for recurrence of gestational diabetes.
AB  - OBJECTIVE: To determine the recurrence rate of gestational diabetes (GDM) during
      a subsequent pregnancy among women who had GDM during an index pregnancy and to
      identify factors associated with the probability of recurrence RESEARCH DESIGN
      AND METHODS: A retrospective longitudinal study was performed in Nova Scotia,
      Canada, of women who were diagnosed as having GDM during a pregnancy between the
      years of 1980 and 1996 and who had at least one subsequent pregnancy during this
      time period. When only the index and first subsequent pregnancy were analyzed,
      the cohort included 651 women. The recurrence rate of GDM in the pregnancy after
      the pregnancy with the initial diagnosis of GDM was determined. Multivariate
      regression models were constructed to model the recurrence of GDM in a subsequent
      pregnancy as functions of potential predictors to estimate RRs and CIs. RESULTS:
      The rate of recurrence of GDM in the pregnancy subsequent to the index pregnancy
      was found to the 35.6% (95% CI = 31.9-39.3%). Multivariate regression models
      showed that infant birth weight in the index pregnancy and maternal prepregnancy
      weight before the subsequent pregnancy were predictive of recurrent GDM.
      CONCLUSIONS: In this large cohort of women, slightly more than one-third of the
      subjects had diabetes in a subsequent pregnancy, which is consistent with
      recurrence rates in other predominately white populations. Strategies to reduce
      the occurrence of neonatal macrosomia and maternal prepregnancy obesity may help
      lower the rate of recurrence of GDM.

PMID- 11315828
TI  - Familial early-onset type 2 diabetes in Chinese patients: obesity and genetics
      have more significant roles than autoimmunity.
AB  - OBJECTIVE: We examined the prevalence of different forms of diabetes in Hong Kong
      Chinese patients with familial early-onset type 2 diabetes and compared their
      clinical features with patients with familial late-onset type 2 diabetes.
      RESEARCH DESIGN AND METHODS: A total of 145 young patients with early-onset
      diabetes (age and age at diagnosis < or = 40 years) and a family history of
      diabetes were studied. They were screened for mutations in the genes encoding
      glucokinase, hepatocyte nuclear factor (HNF)-4alpha, and HNF-1alpha. The
      mitochondrial DNA A-->G at nucleotide 3243 (mt3243) and amyLin S20G mutations
      were studied, and antibodies to GAD (anti-GADs) were also examined. RESULTS: The
      prevalence of putative diabetogenic gene mutations and autoimmune markers were 4%
      for glucokinase, 0% for HNF-4alpha, 5% for HNF-1alpha, 3% for mt3243, 2% for
      amylin 520G, and 4% for anti-GAD. Compared with late-onset patients, the patients
      with early-onset diabetes had a higher prevalence of a parental history of
      diabetes and were generally more obese. When classified by obesity indexes (BMI
      and waist circumference), the obese patients, especially those with early-onset
      diabetes, had a clustering of cardiovascular risk factors and increased rates of
      retinopathy and albuminuria. CONCLUSIONS; Genetic factors (up to 14%) and obesity
      (55%) play more significant roles than autoimmunity (4%) in familial type 2
      diabetes in young Chinese patients. The significance of obesity-related genes and
      other gene-gene and gene-environment interactions in these young patients remains
      to be determined.

PMID- 11315829
TI  - Interactions between variants in the beta3-adrenergic receptor and peroxisome
      proliferator-activated receptor-gamma2 genes and obesity.
AB  - OBJECTIVE: Previous studies have reported modest associations between measures of
      obesity and the Trp64-Arg variant of the beta3-adrenergic receptor (ADRbeta3) and
      the Pro12Ala variant of the peronisome proliferator-activated receptor (PPAR)
      gamma2. We hypothesized that these single gene variants may mark mutations that
      act through convergent pathways to produce synergistic effects on obesity.
      RESEARCH DESIGN AND METHODS: The sample included 453 subjects from 10 large
      Mexican-American families participating in the population-based San Antonio
      Family Heart Study. The effects of each gene variant singly and jointly were
      estimated as fixed effects using the measured genotype approach framework.
      Analyses were conditioned on the pedigree structures to account for the
      correlations among family members. Statistical significance was evaluated by the
      likelihood ratio test with adjustment for age, sex and diabetes status. RESULTS:
      The allele frequencies for the ADRbeta3 Trp64Arg and PPARgamma2 Pro12Ala variants
      were 18 and 12%, respectively. The ADRbeta3 variant was not significantly
      associated with any of the obesity-related traits, but subjects with the PPAR
      gamma2 variant (n = 98) had significantly higher levels of lasting insulin (P =
      0.03), leptin (P = 0.009), and waist circumference (P = 0.03) than those without.
      Subjects with the gene variants (n = 32) had significantly higher BMI, insulin,
      and leprtin levels than those with only the PPARgamma2 variant (n = 66) (P for
      interaction: 0.04, 0.02, and 0.01 for BMI, fasting insulin, and leptin,
      respectively). CONCLUSIONS: Our results suggest that epistatic models with genes
      that have modest individual effects may be useful in understanding the genetic
      underpinnings of typical obesity in humans.

PMID- 11315830
TI  - Disordered eating, body mass, and glycemic control in adolescents with type 1
      diabetes.
AB  - OBJECTIVE: To examine the relationship between disordered eating attitudes and
      behaviors, BMI, and glycemic control in adolescents with type 1 diabetes.
      RESEARCH DESIGN AND METHODS: In a cross-sectional design, 152 adolescents (ages
      11-19 years) completed three scales from the Eating Disorders Inventory (EDI):
      Body Dissatisfaction, Drive for Thinness, and Bulimia. All subjects had diabetes
      for > 1 year. Glycemic control was assessed by glycosylated hemoglobin (HbA1c).
      Height and weight were measured to assess BMI. RESULTS: Adolescents with type 1
      diabetes did not report more disordered eating attitudes and behaviors than the
      normative comparison sample. Male subjects with type 1 diabetes reported fewer
      symptoms of bulimia and female subjects with type 1 diabetes reported greater
      body satisfaction than the normative group. A higher BMI was a significant
      predictor of greater body dissatisfaction, more so for female than male subjects.
      Symptoms of bulimia were associated with older adolescence and female sex. Those
      with more symptoms of bulimia were also more likely to have a higher BMI. Sex
      (female) and body dissatisfaction (more dissatisfied) predicted a stronger desire
      to be thin. Longer duration of disease, more symptoms of bulimia, and obesity all
      predicted poorer glycemic control. CONCLUSIONS: Female patients aged 13-14 years
      seem to be at greatest risk for developing disordered eating patterns. Using the
      clinical cutoff score (> or = 5) of the EDI Bulimia subscale as a screener in
      diabetes clinics may help identify adolescents whose disordered eating patterns
      are likely to compromise their glycemic control.

PMID- 11315831
TI  - Cardiovascular morbidity and mortality associated with the metabolic syndrome.
AB  - OBJECTIVE: To estimate the prevalence of and the cardiovascular risk associated
      with the metabolic syndrome using the new definition proposed by the World Health
      Organization RESEARCH DESIGN AND METHODS: A total of 4,483 subjects aged 35-70
      years participating in a large family study of type 2 diabetes in Finland and
      Sweden (the Botnia study) were included in the analysis of cardiovascular risk
      associated with the metabolic syndrome. In subjects who had type 2 diabetes (n =
      1,697), impaired fasting glucose (IFG)/impaired glucose tolerance (IGT) (n = 798)
      or insulin-resistance with normal glucose tolerance (NGT) (n = 1,988), the
      metabolic syndrome was defined as presence of at least two of the following risk
      factors: obesity, hypertension, dyslipidemia, or microalbuminuria. Cardiovascular
      mortality was assessed in 3,606 subjects with a median follow-up of 6.9 years.
      RESULTS: In women and men, respectively, the metabolic syndrome was seen in 10
      and 15% of subjects with NGT, 42 and 64% of those with IFG/IGT, and 78 and 84% of
      those with type 2 diabetes. The risk for coronary heart disease and stroke was
      increased threefold in subjects with the syndrome (P < 0.001). Cardiovascular
      mortality was markedly increased in subjects with the metabolic syndrome (12.0
      vs. 2.2%, P < 0.001). Of the individual components of the metabolic syndrome,
      microalbuminuria conferred the strongest risk of cardiovascular death (RR 2.80; P
      = 0.002). CONCLUSIONS: The WHO definition of the metabolic syndrome identifies
      subjects with increased cardiovascular morbidity and mortality and offers a tool
      for comparison of results from diferent studies.

PMID- 11315832
TI  - Comprehensive evaluation of community-based diabetic patients: effect of feedback
      to patients and their physicians: a randomized controlled trial.
AB  - OBJECTIVE: To demonstrate improvements in diabetes care stimulated by
      comprehensive evaluation of community-based diabetic patients with feedback to
      the patients and their physicians. RESEARCH DESIGN AND METHODS: A comprehensive
      evaluation of community-based diabetic patients with annotated reporting of
      results to both patients and their physicians (universal intervention) was
      followed by random assignment of 50% of patients to individual counseling
      (randomized intervention). In four communities, two large and two small, 55 type
      1 and 376 type 2 diabetic patients were recruited, evaluated, and reassessed at 1
      year. Outcome measures were HbA1c, serum cholesterol, and systolic and diastolic
      blood pressure. RESULTS: There were significant improvements in all outcome
      measures for type 2 diabetic patients randomized to individual counseling (P =
      0.03; follow-up rate 84%) and significant improvements in all outcome measures
      for all high-risk type 2 patients (highest P value = 0.004; follow-up rate 85%).
      CONCLUSIONS: Comprehensive evaluation of diabetic patients at the community level
      with annotated reporting of results to the patients and their physicians was
      associated with improvement of mean HbA1c, cholesterol, and systolic and
      diastolic blood pressure, particularly in patients in high-risk status for these
      outcome variables. Individual counseling of 50% of patients, randomly selected,
      enhanced these results.

PMID- 11315833
TI  - Chronic care clinics for diabetes in primary care: a system-wide randomized
      trial.
AB  - OBJECTIVE: To evaluate the impact of primary care group visits (chronic care
      clinics) on the process and outcome of care for diabetic patients. RESEARCH
      DESIGN AND METHODS: We evaluated the intervention in primary care practices
      randomized to intervention and control groups in a large-staff model health
      maintenance organization (HMO). Patients included diabetic patients > or = 30
      years of age in each participating primary care practice, selected at random from
      an automated diabetes registry. Primary care practices were randomized within
      clinics to either a chronic care clinic (intervention) group or a usual care
      (control) group. The intervention group conducted periodic one-half day chronic
      care clinics for groups of approximately 8 diabetic patients in their respective
      doctor's practice. Chronic care clinics consisted of standardized assessments;
      visits with the primary care physician, nurse, and clinical pharmacist; and a
      group education/peer support meeting. We collected self-report questionnaires
      from patients and data from administrative systems. The questionnaires were
      mailed, and telephoned interviews were conducted for nonrespondents, at baseline
      and at 12 and 24 months; we queried the process of care received, the
      satisfaction with care, and the health status of each patient. Serum cholesterol
      and HbA1c levels and health care use and cost data was collected from HMO
      administrative systems. RESULTS: In an intention-to-treat analysis at 24 months,
      the intervention group had received significantly more recommended preventive
      procedures and helpful patient education. Of five primary health status
      indicators examined, two (SF-36 general health and bed disability days) were
      significantly better in the intervention group. Compared with control patients,
      intervention patients had slightly more primary care visits, but significantly
      fewer specialty and emergency room visits. Among intervention participants, we
      found consistently positive associations between the number of chronic care
      clinics attended and a number of outcomes, including patient satisfaction and
      HbA1c levels. CONCLUSIONS: Periodic primary care sessions organized to meet the
      complex needs of diabetic patients imrproved the process of diabetes care and
      were associated with better outcomes.

PMID- 11315834
TI  - Epipen as an alternative to glucagon in the treatment of hypoglycemia in children
      with diabetes.
AB  - OBJECTIVE: Fear of a severe hypoglycemic reaction is a major obstacle to
      achieving near-normal plasma glucose levels. Although parenteral glucagon is
      effective in treating these reactions, it is cumbersome to use, causes severe
      nausea, and is impractical in the school setting. Epinephrine is available as a
      premixed injection (Epipen) that may be used by all care providers. Using Epipen
      to treat hypoglycemia may be an effective, safe, and easy-to-use alternative to
      glucagon. RESEARCH DESIGN AND METHODS: Ten children (age 11.7 +/- 2.4 years) with
      type 1 diabetes were studied on two occasions. After an overnight equilibration
      period, hypoglycemia was induced via an insulin pump (1 mU x kg(-1) x min(-1)).
      At a blood glucose level of 2.8 mmol/l, either glucagon (1 mg) or epinephrine
      (0.3 mg), in random order, was administered intramuscularly and responses were
      monitored. RESULTS: Plasma free insulin concentrations were similar in both
      studies. Plasma glucose levels increased by 1.7 +/- 0.2 mmol/l (mean +/- SEM) in
      10 min and by 2.6 +/- 0.2 mmol/l in 15 min with administration of glucagon and
      were not consistently increased with administration of epinephrine (P < 0.01).
      Peak glucagon concentrations after administration of glucagon were >60-fold
      higher than basal concentrations. After administration of epinephrine, peak
      epinephrine levels were 20-fold higher than basal concentrations. CONCLUSIONS:
      Epinephrine does not seem to be an adequate substitute for glucagon in the
      treatment of severe hypoglycemia. The effectiveness of glucagon in reversing
      hypoglycemia and its side effects of nausea and vomiting are likely related to
      the markedly supraphysiologic plasma levels achieved with the standard
      intramuscular dose.

PMID- 11315835
TI  - Therapeutic footwear for the neuropathic foot: an algorithm.
AB  - Neuropathy may bring about changes in form and function of the foot, which may
      lead to ulceration and progressive deformity. These manifestations often require
      specially adapted footwear. A comprehensive concept of the medical, functional,
      and technical requirements for this type of footwear is still lacking to date. In
      this article, We present an algorithm that should facilitate prescription and
      manufacture of adequate shoes. This algorithm attempts to establish a link
      between the requirements from a medical and functional point of view and the
      technical possibilities of orthopedic shoe technology.

PMID- 11315836
TI  - Improved glycemic control and enhanced insulin sensitivity in type 2 diabetic
      subjects treated with pioglitazone.
AB  - OBJECTIVE: To elucidate the effects of pioglitazone treatment on glucose and
      lipid metabolism in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: A
      total of 23 diabetic patients (age 30-70 years BMI < 36 kg/m2) who being treated
      with a stable dose of sulfonylurea were randomly assigned to receive either
      placebo (n = 11) or pioglitazone (45 mg/day) (n = 12) for 16 weeks. Before and
      after 16 weeks of treatment, all subjects received a 75-g oral glucose tolerance
      test (OGTT) and hepatic peripheral insulin sensitivity was measured with a two
      step euglycemic insulin (40 and 160 mU x min(-1) x m(-2) clamp performed with 3
      [3H]glucose and indirect calorimetry HbA1c measured monthly throughout the study
      period. RESULTS: After 16 weeks of pioglitazone treatment, the fasting plasma
      glucose (FPG; 184 +/- 15 to 135 +/- 11 mg/dl, P < 0.01), mean plasma glucose
      during OGTT(293 +/- 12 to 225 +/- 14 mg/dl, P < 0.01), and HbA1c (8.9 +/- 0.3 to
      7.2 +/- 0.5%, P < 0.01 ) decreased significantly without change in fasting or
      glucose-stimulated insulin/C-peptide concentrations. Fasting plasma free fatty
      acid (FFA; 647 +/- 39 to 478 +/- 49) microEq/l, P < 0.01) and mean plasma FFA
      during OGTT (485 +/- 30 to 347 +/- 33 microEq/l, P < 0.01) decreased
      significantly after pioglitazone treatment. Before and after pioglitazone
      treatment, basal endogenous glucose prodution (EGP) and FPG were strongly
      correlated (r = 0.67, P < 0.01). EGP during the first insulin clamp step was
      significantly decreased after pioglitazone treatment (P < 0.05) whereas insulin
      stimulated total and nonoxidative glucose disposal during the second insulin
      clamp was increased (P < 0.01). The change in FPG was related to the change in
      basal EGP, EGP during the first insulin clamp step, and total glucose disposal
      during the second insulin clamp step. The change in mean plasma glucose
      concentration during the OGGTT was strongly related to the change in total body
      glucose disposl during the second insulin clamp step. CONCLUSIONS: These results
      suggest that pioglitazone therapy in type 2 diabetic patients decreases lasting
      and postprandial plasma glucose levels by improving hepatic and peripheral
      (muscle) tissue sensitivity to insulin.

PMID- 11315837
TI  - Additive glucose-lowering effects of glucagon-like peptide-1 and metformin in
      type 2 diabetes.
AB  - OBJECTIVE: The incretin hormone glucagon-like peptide-1 (GLP-1) reduces plasma
      glucose in type 2 diabetic patients by stimulating insulin secretion and
      inhibiting glucagon secretion. The biguanide metformin is believed to lower
      plasma glucose without affecting insulin secretion. We conducted this study to
      investigate the effect of a combination therapy with GLP-1 and metformin, which
      could theoretically be additive, in type 2 diabetic patients. RESEARCH DESIGN AND
      METHODS: In a semiblinded randomized crossover study, seven patients received
      treatment with metformin (1,500 mg daily orally) alternating with GLP-1
      (continuous subcutaneous infusion of 2.4 pmol x kg(-1) x min(-1)) alternating
      with a combination of metformin and GLP-1 for 48 h. Under fixed energy intake, we
      examined the effects on plasma glucose, insulin, C-peptide, glucagon, and
      appetite. RESULTS: Fasting plasma glucose (day 2) decreased from 13.9 +/- 1 (no
      treatment) to 11.2 +/- 0.4 (metformin) and 11.5 +/- 0.5 (GLP-1) and further
      decreased to 9.4 +/- 0.7 (combination therapy) (P = 0.0005, no difference between
      monotherapy with GLP-1 and metformin). The 24-h mean plasma glucose (day 2)
      decreased from 11.8 +/- 0.5 (metformin) and 11.7 +/- 0.8 (GLP-1) to 9.8 +/- 0.5
      (combination) (P = 0.02, no difference between GLP-1 and metformin). Insulin
      levels were similar between the three regimens, but glucagon levels were
      significantly reduced with GLP-1 compared with metformin (P = 0.0003).
      Combination therapy had no additional effect on appetite scores. CONCLUSIONS:
      Monotherapy with GLP-1 and metformin have equal effects on plasma glucose and
      additive effects upon combination.

PMID- 11315838
TI  - alpha-Dicarbonyls increase in the postprandial period and reflect the degree of
      hyperglycemia.
AB  - OBJECTIVE: Chronic hyperglycemia is known to increase tissue glycation and
      diabetic complications, but controversy exists regarding the independent role of
      increased postprandial glucose excursions. To address this question, we have
      studied the effect of postprandial glycemic excursions (PPGEs) on levels of
      methylglyoxal (MG) and 3-deoxyglucosone (3-DG), two highly reactive precursors of
      advanced glycation end products (AGEs). RESEARCH DESIGN AND METHODS: We performed
      4-month crossover studies on 21 subjects with type 1 diabetes and compared the
      effect of premeal insulin lispro or regular insulin on PPGEs and MG/3-DG
      excursions. PPGE was determined after standard test meal (STMs) and by frequent
      postprandial glucose monitoring. HbA1c and postprandial MG and D-lactate were
      measured by HPLC, whereas 3-DG was determined by gas chromatography/mass
      spectroscopy. RESULTS: Treatment with insulin lispro resulted in a highly
      significant reduction in PPGEs relative to the regular insulin-treated group (P =
      0.0005). However, HbA1c levels were similar in the two groups, and no
      relationship was observed between HbA1c and PPGE (P = 0.93). Significant
      postprandial increases in MG, 3-DG, and D-lactate occurred after the STM.
      Excursions of MG and 3-DG were highly correlated with levels of PPGE (R = 0.55, P
      = 0.0002 and R = 0.61, P = 0.0004; respectively), whereas a significant inverse
      relationship was seen between PPGE and D-lactate excursions (R = 0.40, P = 0.01).
      Conversely, no correlation was observed between HbAlc and postprandial MG, 3-DG,
      or D-lactate levels. CONCLUSIONS: Increased production of MG and 3-DG occur with
      greater PPGE, whereas HbA1c does not reflect these differences. Reduced PPGE also
      leads to increased production of D-lactate, indicating a role for increased
      detoxification in reducing MG levels. The higher postprandial levels of MG and 3
      DG observed with greater PPGE may provide a partial explanation for the adverse
      effects of glycemic lability and support the value of agents that reduce glucose
      excursions.

PMID- 11315839
TI  - Serum 8-hydroxy-guanine levels are increased in diabetic patients.
AB  - OBJECTIVE: The production of reactive oxygen species is increased in diabetic
      patients, especially in those will poor glycemic control. We have investigated
      oxidative damage in type 2 diabetic patients using serum 8-hydroxyguanine (8-OHG)
      as a biomarker. RESEARCH DESIGN AND METHODS: We studied 41 type 2 diabetic
      patients and compared them with 3 nondiabetic control subjects. Serum 8-OHG
      concentration was assayed using high-pressure liquid chromatography. RESULTS: The
      type 2 diabetic patients had significantly higher concentrations of 8-OHG in
      their serum than the control subjects (5.03 +/- 0.69 vs. 0.96 +/- 0.15 pmol/ml P
      < 0.01). There was no association between the levels of 8-OHG and HbA1c. We also
      could not and any correlation between serum 8-OHG levels and age, duration of
      diabetes, serum lipids, or creatinine or albumin exeretion rate. Creatinine
      clearance showed marginal correlation with serum 8-OHG levels (P = 0.06). Among
      the diabetic patients, those with proliferative retinopathy had significantly
      higher 8-OHG levels than those with nonproliferative retinopathy or without
      retinopathy. Likewise, the serum 8-OHG levels in patients who had advanced
      nephropathy (azotemia) were higher than in patients with normoalbuminuria,
      microalbuminuria, or overt proteinuria. CONCLUSIONS: Our findings show that
      measuring serum 8-OHG is a novel convenient method for evaluating oxidative DNA
      damage. Diabetic patients, especially those with advanced microvascular
      complications, had significantly higher serum 8-OHG levels; this suggests that
      such changes may contribute to the development of microvascular complications of
      diabetes.

PMID- 11315840
TI  - Sulfonylurea treatment of type 2 diabetic patients does not reduce the
      vasodilator response to ischemia.
AB  - OBJECTIVE: Sulfonylureas block the activation of vascular potassium-dependent ATP
      channels and impair the vasodilating response to ischcmia in nondiabetic
      individuals, but it is not know whether this occurs in type 2 diabetic patients
      under chronic treatment with these drugs. Glimepiride, a new sulfonylurea,
      apparently has no cardiovascular interactions. The aim of our study was to
      compare the effect of the widely used compound glibenclamide, the pancreas
      specific glimepiride, and diet treatment alone on brachial artery response to
      acute forearm ischemia. RESEARCH DESIGN AND METHODS: Brachial artery examination
      was performed by a high-resolution ultrasound technique on 20 type 2 diabetic
      patients aged mean +/- SD) 67 +/- 2 years and on 18 nondiabetic patients matched
      for age, hypertension, and dislipidemia. Diabetic subjects underwent three
      separate evaluations at the end of each 8-week treatment period, during which
      they received glibenclamide, glimepiride, or diet alone according to crossover
      design. Scans were obtained before and after 4.5 min of forearm ischemia.
      Postischemic vasodilation and hyperemia were expressed as percent variations in
      vessel diameter and blood flow. RESULTS: Postischemic vasodilation and hyperemia
      were, respectively, 5.42 +/- 0.90 and 331 +/- 38% during glibenclamide, 5.46 +/-
      0.69 and 326 +/- 28% during glimepiride, and 5.17 +/- 0.64 and 357 +/- 35% during
      diet treatment (NS). These results were similar to those found in the nondiabetic
      patients (6.44 +/- 0.68 and 406 +/- 42%, NS). CONCLUSIONS: In type 2 diabetic
      patients, the vasodilating response to forearm ischemia was the same whether
      patients were treated with diet treatment alone or with glibenclamide or
      glimepiride at blood glucose-lowering equipotent closes.

PMID- 11315841
TI  - Midpregnancy serum C-peptide concentration and subsequent pregnancy-induced
      hypertension.
AB  - OBJECTIVE: To test the hypothesis that elevated midpregnancy serum insulin (IRI)
      and C-peptide (CP) concentrations are associated with later development of
      pregnancy-induced hypertension (PIH), independent of prepregnancy obesity and
      midpregnancy blood pressure. RESEARCH DESIGN AND METHODS: In this prospective
      study, a cohort of normotensive women, ages > or = years performed a 50-g glucose
      challenge test at 24-30 weeks' gestational age. Blood samples were collected
      after an overnight fast and 1 h after glucose ingestion. Serum IRI and CP
      concentrations were measured in each sample. Maternal height, blood pressure and
      proteinuria were measured at the time of glucose challenge testing and after 36
      weeks' gestational age. RESULTS: Of 320 subjects enrolled 44 women (13.8%) had
      subsequent PIH. Crude odds ratios (ORs) for devevelopment of PIH associated with
      each 1 U rise in log fasting IRI, log lasting CP. and glucosed-induced increase
      in CP (expressed as log [postprandial CP/fasting CP]) were 2.0 (95% CI 1.3-3.3),
      1.8 (CI 1.2-2.7), and 2.3 (CI 1.1-4.9) respectively. After controlling for
      prepregnancy BMI, gestational age, and midpregnancy mean arterial pressure,
      adjusted ORs corresponding to log fastig IRI and CP for the development of PIH
      were 1.3 (95% CI 0.7-2.3) and 1.7 (CI 1.1-2.7) respectively, and, afterq
      adjustment for fasting CP, the adjusted OR of the glucose-induced rise in log CP
      was 3.7 (CI 1.5-9.3). CONCLUSIONS: Mid-pregnancy tasting and postoral glucose CP
      levels are associated with subsequent development of PIH, independent of maternal
      obesity and midpregnancy baseline blood pressure. These findings many reflect an
      amplified beta3-cell response to glycemic stimulus, similar to that found in
      states of insulin resistance, that appears to be independently associated with
      PIH.

PMID- 11315842
TI  - Glycemic control is related to the morphological severity of diabetic
      sensorimotor polyneuropathy.
AB  - OBJECTIVE: The aim of the current study was to determine the independent clinical
      risk factors for predicting morphological severity of distal diabetic
      sensorimotor polynecuropathy (DSP) as determined by fiber density (FD) on sural
      nerve biopsy. RESEARCH DESIGN AND METHODS: A total of 89 patients with both type
      1 and type 2 diabetes, ascertained from a large therapeutic randomized clinical
      trial, were included in this observational cohort study. Morphological severity
      of DSP was expressed as the myelinated FD in the sural nerve biopsy General
      linear models were used to assess the relationship between the morphological
      severity of DSP and various clinical risk factors. RESULTS: Glycated hemoglobin
      (GHb) was significantly related to FD in univariate and multivariate regression
      analyses. This relationship was present in models in which GHb was handled either
      as a continuous variable or as a categorical variable with the highest
      significance level, with a GHb cutoff level of 9%. After dividing patients into
      groups with optimal to moderate GHb < or = 9%) and suboptimal (GHb >9%) glycemic
      control, the difference in FD between the two groups ranged between 3,461 and
      2,334 per mm2. FD was also significantly related to duration of diabetes and age
      of the patient. CONCLUSIONS: The severity of peripheral DSP expressed by
      morphological criteria was significantly related to glycemic control in type 1
      and type 2 diabetic patients. Inconsistent with previously published
      electrophysiological data demonstrating a correlation between height and
      conduction velocity, increasing height is not associated with morphological
      severity. Based on the results of the present study, it might be hypothesized
      that improving glycemic control will lessen severity of DSP in terms of FD loss
      in subjects with diabetes.

PMID- 11315843
TI  - TNFRSF1B in genetic predisposition to clinical neuropathy and effect on HDL
      cholesterol and glycosylated hemoglobin in type 2 diabetes.
AB  - OBJECTIVE: Genetic variation in the tumor necrosis factor (TNF) receptor 2 gene
      (TNFRSF1B) has shown association with insulin resistance in type 2 diabetes,
      hypercholesterolemia, coronary artery disease, and essential hypertension. Here
      we tested the TNFRSF1B marker used in the latter studies in type 2 diabetes
      patients. RESEARCH DESIGN AND METHODS: A case-control study of a microsatellite
      marker with five alleles (CA13- CA17) in intron 4 of TNFRSF1B was performed in
      357 well-characterized white patients and 183 healthy control subjects. RESULTS:
      The CA16 allele was associated with clinical neuropathy (frequency = 27% in 69
      patients with the condition versus 16% in 230 subjects without the condition;
      chi2 = 9.0, P = 0.011; odds ratio = 2.1 [95% CI 1.2-3.8]). No association was
      seen with other complications or diabetes itself. The CA16 allele tracked with
      elevation plasma HDL cholesterol (1.3 +/- 0.2, 1.2 +/- 0.4, and 1.1 +/- 0.2 for
      CA16/CA16, CA16/-, and -/-, respectively; n = 9, 110, and 218, respectively; P =
      0.009) and reduction in plasma glycosylated hemoglobin (6.6 +/- 0.3, 8.3 +/- 0.2,
      and 8.1 +/- 0.1 for CA16/CA16, CA16/-, and -/-, respectively; n = 9, 102, 205,
      respectively; P = 0.007) Significance remained after Bonferroni correction for
      multiple testing. CONCLUSIONS: Genetic variation in or near TNFRSF1B may
      predispose clinical neuropathy, reduced glycosylated hemoglobin, and increased
      HDL cholesterol in type 2 diabetes patients. The latter could be part of a
      protective response.

PMID- 11315844
TI  - Combination therapies with insulin in type 2 diabetes.

PMID- 11315845
TI  - Response to Bell: industry perspective.

PMID- 11315846
TI  - Placebo-controlled trials of new drugs: ethical considerations.

PMID- 11315847
TI  - Placebo-controlled trials in type 2 diabetes.

PMID- 11315848
TI  - Postprandial blood glucose. American Diabetes Association.

PMID- 11315849
TI  - American Diabetes Association 60th Scientific Sessions, 2000: glucose tolerance,
      diabetes and cancer, glycemic control, monitoring, and related topics.

PMID- 11315850
TI  - Rising incidence of type 1 diabetes in Germany: 12-year trend analysis in
      children 0-14 years of age.

PMID- 11315851
TI  - Prevalence of maturity-onset diabetes of the young mutations in Brazilian
      families with autosomal-dominant early-onset type 2 diabetes.

PMID- 11315852
TI  - Administration of troglitazone, but not pioglitazone, reduces insulin resistance
      caused by short-term dexamethasone (DXM) treatment by accelerating the metabolism
      of DXM.

PMID- 11315853
TI  - Longitudinal analysis of blood pressure, lipid, and glycemic control in diabetic
      patients with nephropathy attending a hospital outpatient clinic and their
      relationship to renal function, mortality, and cardiovascular morbidity.

PMID- 11315854
TI  - Microalbuminuria, high blood pressure burden, and nondipper phenomenon: an
      interaction in normotensive type 1 diabetic patients.

PMID- 11315855
TI  - Bone mineral density, type 1 diabetes, and celiac disease.

PMID- 11315856
TI  - Serious hypoglycemia: Munchausen's syndrome?

PMID- 11315857
TI  - Serum leptin concentrations in young smokers with type 1 diabetes.

PMID- 11315858
TI  - An avoidable cause of false home glucose measurements.

PMID- 11315859
TI  - Do all women require intensive retinal surveillance during pregnancy?

PMID- 11315860
TI  - Oral glucose tolerance test indexes for insulin sensitivity and secretion based
      on various availabilities of sampling times.

PMID- 11315861
TI  - Diabetes in pregnancy.
AB  - The following review considers briefly most aspects of the care of the woman with
      established diabetes, gestational diabetes and impaired glucose tolerance. Where
      possible, reference is made to recent publications, but much of our current
      practice is based on old research and opinions. However, a review of current
      practice clearly shows that existing research is not being put into practice. The
      controversies surrounding the relevance of impaired glucose tolerance are
      discussed, and the results of existing clinical trials are eagerly awaited.

PMID- 11315862
TI  - Renal disorders in pregnancy.
AB  - This update discusses the mechanisms responsible for gestational augmentation of
      renal haemodynamics, the role of urinary tract infections in preterm labour and
      paediatric development, and the importance of post-delivery infection and its
      relationship to previous catheterization. Pregnancy in women with chronic renal
      disease, on dialysis or with a kidney transplant, is reviewed emphasizing the
      risks in those women who already have problems pre-pregnancy, the problems
      associated with medication used during pregnancy and the impact of pregnancy on
      long-term prognosis. New information about altered glomerular physiology in pre
      eclampsia is assessed.

PMID- 11315863
TI  - Platelet disorders in pregnancy.
AB  - Before the advent of automated cell counters, thrombocytopenia was looked for and
      identified after a clinical question. With automation, thrombocytopenia in
      pregnancy was commonly found, and with its commonality its clinical meaning went
      out of focus. For the majority of women, thrombocytopenia is benign and, as a
      marker of fetal thrombocytopenia, the value of maternal thrombocytopenia is
      almost non-existent.

PMID- 11315864
TI  - Management of the pregnant mother with malignant conditions.
AB  - A malignancy discovered in pregnancy is often difficult to manage; the optimal
      maternal therapy has to be balanced with the fetal well-being. Generally, the
      cancer is managed as though the patient is not pregnant. For the various site
      specific cancers, surgery is the main modality of treatment; this should be
      individualized. Chemotherapeutic agents are highly teratogenic in the first
      trimester, with some adverse effects when used after 12 weeks' gestation. The
      overall survival rate for pregnancy-associated breast cancer is poor; the reasons
      for this are discussed. For cervical cancer, delivery by caesarean section
      appears to be the method of choice, with significantly better survival rates
      compared with those who deliver vaginally. Other gynaecological and non
      gynaecological malignancies are discussed.

PMID- 11315865
TI  - The surgical management of postpartum haemorrhage.
AB  - This review summarizes the options available for the management of postpartum
      haemorrhage when ecbolic agents have failed to control the bleeding and an
      obvious rectifiable problem such as retained placental fragments, lower genital
      tract trauma, uterine inversion or uterine rupture have been excluded or dealt
      with. The review covers the range of surgical options but gives an in-depth
      explanation of the more recent developments such as uterine brace sutures, the
      use of the Sengstaken-Blakemore tube and embolization procedures.

PMID- 11315866
TI  - The future of intrapartum fetal pulse oximetry.
AB  - Fetal pulse oximetry has undergone a remarkable evolution since its conception
      over 10 years ago. A number of important observations, including the recent
      publication of a large randomized clinical trial, have provided further insight
      into our understanding of intrapartum fetal physiology and intrapartum fetal
      assessment. The purpose of this paper is to review significant developments in
      this technology over the past 2 years and to propose paths for future clinical
      research.

PMID- 11315867
TI  - Fetal electrocardiogram waveform analysis in labour.
AB  - The fetal electrocardiogram recorded during labour has so far been used for heart
      rate recording only. Extensive experimental, bioengineering and clinical research
      for more than 25 years on changes in the morphology of the electrocardiogram have
      provided more detailed information on fetal reactions to the stress and strain of
      labour. ST waveform analysis has been shown to provide new parameters that have
      the ability to monitor intrapartum hypoxia, thereby not only reducing the risk of
      the baby being born with hypoxia, but also significantly reducing the number of
      operative interventions.

PMID- 11315868
TI  - Lactate measurements in scalp and cord arterial blood.
AB  - Lactate has been measured to evaluate fetal metabolic acidosis for some decades.
      However, not until the past few years have reliable lactate meters become
      available for bedside obstetric practice. The new technology, which requires only
      5 microl blood, has reduced the sampling failure rate of fetal scalp blood to
      almost nil. A growing body of evidence has also shown lactate to be good at
      predicting neonatal outcome.

PMID- 11315869
TI  - Update on oxygen radical disease in neonatology.
AB  - An increasing number of articles related to free radicals in the newborn period
      is published. The hypothesis that there exists a socalled 'Oxygen radical disease
      of neonatology' has not been proven but an increasing body of evidence seems to
      indicate that free radicals are involved in several disease processes leading to
      conditions such as chronic lung disease, retinopathy of prematurity, necrotizing
      enterocolitis and periventricular leukomalacia. There are also accumulating data
      implying the involvement of reactive oxygen species and oxidative stress in
      signal transduction and they therefore perhaps affect growth and development. In
      the last year there have been no new breakthroughs in antioxidant therapy.

PMID- 11315870
TI  - Early prenatal diagnosis of major congenital heart defects.
AB  - Specialized fetal echocardiography at 18 to 22 weeks for high-risk groups is well
      established as being sensitive and specific for most cardiac abnormalities. Early
      fetal echocardiography (< 16(+0) weeks, i.e. 16 weeks and 0 days) is a feasible
      alternative to mid second trimester scanning for families at risk of congenital
      heart disease. Two main areas have contributed to the increasing interest in
      first and early second trimester fetal echo. The recognition of the association
      between increased nuchal translucency and structural heart abnormalities has led
      to the identification of an important high-risk group at 11 to 14 weeks.
      Furthermore, the use of modern ultrasound technology has allowed greater
      utilization of transabdominal scanning in addition to the transvaginal route.
      Most major structural heart defects can accurately be diagnosed from the late
      first trimester of pregnancy and many families at-risk can be reassured of
      'normality' of cardiac connections at an early stage. Some lesions may evolve
      throughout pregnancy and therefore early scans should not replace mid trimester
      fetal echocardiography.

PMID- 11315871
TI  - Antenatal assessment of the growth restricted fetus.
AB  - Babies who are small due to intrauterine growth restriction are at higher risk
      for poor perinatal and long-term outcome than those who are appropriately grown.
      Through multiple antenatal testing modalities a sequence of deteriorating fetal
      status can be documented in such cases. The nature of this compromise is best
      reflected by the combination of fetal biometry, biophysical profile scoring and
      arterial and venous Doppler. This combination accurately defines fetal states and
      therefore risk of stillbirth or poor transition to extrauterine life. In the
      preterm neonate, fetal factors, gestational age and neonatal course interact
      significantly to impact on short- and long-term outcomes. The potential for
      iatrogenic prematurity is great and ongoing appraisal of peripartum management is
      critical. An integrated management protocol accounting for these factors is
      examined in this review.

PMID- 11315872
TI  - Outcome of fetuses with increased nuchal translucency.
AB  - Recent reports on nuchal translucency screening in unselected patient populations
      show results that are comparable with those reported by the thus far largest
      series on screening for Down's syndrome based on maternal age and nuchal
      translucency measurement. Much interest is focused on the prognostic value of
      increased nuchal translucency in fetuses with normal chromosomes. Increased
      nuchal translucency is regarded as a clear sign of declining fetal health, which
      can be associated with fetal demise, structural anomalies, rare genetic
      syndromes, and in particular congenital heart defects. A clear association is
      demonstrated between nuchal translucency above the 99th centile and congenital
      cardiac defects. Such a finding should prompt specialized echocardiography.
      However, on the whole the sensitivity of nuchal translucency screening is too low
      to consider this as the sole criterion to screen for critical heart defects.

PMID- 11315873
TI  - Integrating antenatal Down's syndrome screening.
AB  - Statistical modelling is used to predict screening detection and false-positive
      rates for policies using different marker combinations and screening modalities.
      Parameters are derived wherever possible from meta-analyses. Screening with four
      serum markers yields a similar detection rate in the first trimester as it does
      in the second, and both have a similar detection rate to that of ultrasound
      nuchal translucency screening. Ultrasound anomaly screening has a low detection
      rate. The integration of the different screening modalities can yield very high
      detection rates. Some methods of integration are preferable to others. The
      concurrent use of first trimester serum markers and ultrasound nuchal
      translucency is the most practical. The combination of three modalities with
      nondisclosure of the intermediate results is more efficient, but the gain in
      detection is too small to warrant the wait for up to 4 weeks for results. The
      sequential use of modalities with intermediate disclosure is more practical but
      will generate higher false-positive rates.

PMID- 11315874
TI  - The value of minor ultrasound markers for fetal aneuploidy.
AB  - As a result of improvements in ultrasound image quality and scanning technique,
      an increasing number of subtle morphological changes in fetal anatomy have been
      identified in the second trimester. Most of these ultrasound features were
      originally described as normal variants of development with no clinical
      significance. However, subsequent studies in high-risk populations showed that
      some of these variants were more prevalent in fetuses with chromosomal defects
      and therefore proposed as prenatal markers for the detection of aneuploidy. The
      implications for pregnancy management when one of these so-called minor
      ultrasound markers is detected have been a matter of continuous controversy in
      the field of prenatal diagnosis and yet the definitive answer on their clinical
      significance in the low-risk population is still debated.

PMID- 11315875
TI  - Twin-twin transfusion syndrome: etiology, severity and rational management.
AB  - The twin-twin transfusion syndrome is a serious complication of monochorionic
      twin pregnancies. Partly as a result of an inadequate understanding of the
      pathophysiology of the syndrome, there is a lack of consensus in clinical
      management. We sought to review the available information on the etiology of twin
      twin transfusion syndrome, to identify parameters that contribute to the severity
      of the syndrome, and propose a rational management plan based on pathophysiology,
      clinical presentation and the efficacy of therapies. We therefore amalgamated
      recent advances in twin-twin transfusion syndrome computer modelling and clinical
      studies, particularly on therapeutic outcomes. We found that the oligo
      polyhydramnios sequence that defines twin-twin transfusion syndrome prenatally
      represents a wide continuum of severity in the imbalance between the
      fetoplacental circulations of both twins. In severe twin-twin transfusion
      syndrome cases, in which the circulatory imbalance deteriorates beyond fetal
      control, fetoscopic laser therapy of all anastomoses along the placental vascular
      equator is predicted to have significantly better survival rates and fewer
      neurological sequelae than amnioreduction. In contrast, mild twin-twin
      transfusion syndrome cases have better outcomes after one or at most a few
      amnioreductions than laser therapy, as a result of significantly fewer procedure
      related risks. In conclusion, optimal individual therapy may possibly achieve an
      85% survival rate in twin-twin transfusion syndrome, but requires advancement in
      non-invasive criteria that predict the severity of the syndrome. Identifying such
      criteria is a future challenge. For the interim, twin-twin transfusion syndrome
      diagnosed before 26 weeks' gestation has significantly better survival rates and
      fewer neurological sequelae after laser therapy than amnioreduction. Twin-twin
      transfusion syndrome diagnosed after 26 weeks can best be treated by
      amnioreduction, or delivery. Contrary to previous claims, fetoscopic laser
      therapy has outgrown its experimental status. Although improvements in technique
      and technology are likely, laser placental ablation has a firm scientific and
      clinical basis.

PMID- 11315876
TI  - The role of three-dimensional ultrasound in obstetrics.
AB  - Three-dimensional ultrasound is a relatively new imaging modality with several
      potential advantages over conventional two-dimensional sonography. There is now
      increasing evidence that three-dimensional ultrasound can in many ways assist in
      the examination of the fetus. The enthusiasm generated by some groups, however,
      is not universally shared. It is the aim of this review to summarize the
      contemporary role of three-dimensional ultrasound in obstetric sonography by
      giving a critical appraisal of the relevant literature published recently, with
      emphasis on first and second trimester anatomy and fetal organ and placenta
      volumetry.

PMID- 11315877
TI  - Fetal surgery for myelomeningocele.
AB  - Myelomeningocele is a devastating birth defect affecting a significant number of
      live births worldwide. Prenatal repair of myelomeningocele has been performed in
      the United States for 5 years with mixed results. The initial intent was to
      preserve distal neurological function by covering the exposed spinal cord.
      Although there has been relatively little effect on distal sensorimotor function,
      prenatal repair serendipitously led to an apparent reduction in hindbrain
      herniation and a possible decreased need for ventriculoperitoneal shunting. The
      long-term clinical consequences of these findings are not clear. What is clear,
      however, is that further study in the form of a prospective, randomized trial is
      mandatory.

PMID- 11315878
TI  - Bibliography. Current world literature. Maternal-fetal medicine. Prenatal
      diagnosis.

PMID- 11315880
TI  - Data requirements in a model of the natural history of Alzheimer's disease.
AB  - The "natural history" of Alzheimer's disease (AD) is discussed in terms of the
      data required in a general, discrete-time, non-homogeneous Markov model. The
      proposed model differs from similar models reported in the literature because
      mortality is disaggregated into AD-specific mortality and competing mortality due
      to other causes. Data are reviewed from the literature for AD incidence, and
      rates of disease progression and mortality. We conduct a preliminary sensitivity
      analysis using the reviewed data as base-case. The model shows that survival is
      sensitive to the modelling assumptions concerning mortality. This observation
      could have important consequences for studies that assess the cost of care
      following therapeutic interventions.

PMID- 11315881
TI  - Using a continuous time hidden Markov process, with covariates, to model bed
      occupancy of people aged over 65 years.
AB  - Previously, the application of a continuous time hidden Markov model with
      discrete states was used to model geriatric inpatient behaviour. This was itself
      built on research using a discrete deterministic model to represent the flow of
      geriatric patients around departments of geriatric medicine. This paper uses the
      continuous time hidden Markov models and includes the effect of covariates, age
      and sex, in the model. Fitting the models we can visually see that the two
      compartment models provides estimates that are much closer to those observed in
      the data. The addition of covariates provides us with evidence of a difference in
      length of stay between men and women. However, even significant alterations to
      the mean age of patients in the model does not effect the length of stay.

PMID- 11315882
TI  - Developing a Bayesian belief network for the management of geriatric hospital
      care.
AB  - Resource management is an essential feature of hospital management. This is
      especially true for geriatric services, as older people often have complex
      medical and social needs. Hospital management should benefit from an explanatory
      model that provides predictions of duration of stay and destination on discharge.
      We describe how a Bayesian belief network models the behaviour of geriatric
      patients using predictive variables: personal details, admission reasons and
      dependency levels. This approach is illustrated using data on 4,722 patients
      admitted to geriatric medicine at St. George's Hospital, London; distributions of
      the patient outcome given typical values of the predictive variables are
      provided.

PMID- 11315883
TI  - A simulation study of the winter bed crisis.
AB  - The winter bed crisis is a cyclical phenomenon which appears in British hospitals
      every year, two or three weeks after Christmas. The crisis is usually attributed
      to factors such as the bad weather, influenza, older people, geriatricians, lack
      of cash or nurse shortages. However, a possible alternative explanation could be
      that beds within the hospital are blocked because of lack of social services for
      discharge of hospital patients during the Christmas period. Adopting this
      explanation of why the bed crisis occurs, the problem was considered as a queuing
      system and discrete event simulation was employed to evaluate the model
      numerically. The model shows that stopping discharges of rehabilitating patients
      for 21 days accompanied by a cessation of planned patients for 14 days
      precipitate a bed crisis when the planned admissions recommence. The extensive
      "what-if" capabilities of such models could be proved to be crucial to the
      designing and implementation of possible solutions to the problem.

PMID- 11315884
TI  - Implications of mixed exponential occupancy distributions and patient flow models
      for health care planning.
AB  - There is considerable evidence that the distribution of the length of time that a
      patient occupies a bed in a hospital department is best described by a sum of two
      or three exponential terms, because of the presence of acute care,
      rehabilitation, and possibly long term care patients in the department. The
      patient flow models implied by these mixed exponential distributions are
      presented and fitting them to observed data when the admission rate fluctuates is
      discussed. Unlike single exponential distributions, mixed exponential
      distributions imply that the average length of stay of patients currently
      resident in the department is much longer than the average length of stay of a
      group of patients discharged over a period of time, so that the latter way of
      measuring will not correctly indicate what portion of the resources are being
      used by rehabilitation and long term care patients. Also, the expected additional
      length of stay increases dramatically with the time already spent in the
      department. Applications to predicting the effects of policy changes and to long
      term monitoring of hospital departments are presented. Two American hospitals are
      analyzed. The occupancy times in the government supported hospital follow a mixed
      exponential distribution similar to those found in the United Kingdom, but in the
      private hospital they fit a single exponential distribution, indicating markedly
      different management practices.

PMID- 11315885
TI  - Practical experience with bed occupancy management and planning systems: an
      Australian view.
AB  - Pressure is increasing on hospitals to do more with fewer resources. The
      appropriate management of hospital beds is crucial. The author's practical
      experience of applying the Harrison and Millard Flow Model (BOMPS) and Sorensen's
      multi-phased bed model to aspects of the public hospital system in South
      Australia are detailed. These techniques can provide decision makers with
      improved bed management information. Modelling enables the effects of decisions
      to be analyzed before implementation. Further development of these tools,
      together with other modelling approaches, cannot be ignored as a means of
      improving the strategic management of hospital beds.

PMID- 11315886
TI  - Modelling hospital and social care bed occupancy and use by elderly people in an
      English health district.
AB  - The paper confirms that exponential equations can be used to model the total
      system and sub-systems of institutional health and social care for elderly people
      using bed occupancy census data for 6,068 elderly aged 65 and over. Two streams
      of flow were present in NHS acute hospitals, Local Authority residential homes
      and independent sector nursing homes. Three streams of flow were present in the
      overall data set and in the NHS geriatric hospital beds, NHS psychiatry beds and
      independent sector residential care homes. In total 22% of patients/residents
      stayed an average of 24 days (short stay), 69% for 825 days (medium stay) and 9%
      for 3,384 days (long stay). In both sexes, the older a patient/resident, the
      longer the time they occupied short stay beds and the shorter the time they
      occupied long stay beds.

PMID- 11315887
TI  - Analysis of bed usage and occupancy following the introduction of geriatric
      rehabilitative care in a hospital in Huesca, Spain.
AB  - The decision support system BOMPS (Bed Occupancy Management and Planning
      Software) is used to document the effects on bed usage and occupancy of policy
      changes in the role of the provincial hospital of Huesca, Spain. A preliminary
      analysis of data for 1,834 hospital discharges during the period 1987 to 1996
      showed that there was an increase in hospital activity. Estimates of bed usage
      and occupancy during a calendar year were calculated from aggregated weekly
      census data. Bed usage by short-stay patients increased following the
      introduction of rehabilitative care. Bed usage by long-stay patients decreased
      immediately following the introduction of rehabilitative care, however, the time
      between admission and census for long-stay patients decreased only after a number
      of years.

PMID- 11315888
TI  - Health care modelling and clinical practice. Theoretical exercise or practical
      tool?
AB  - The paper looks at potential uses of health care modelling techniques in day-to
      day clinical practice, adopting the viewpoint of a specialist in geriatric
      medicine. After a brief review of the recent literature on the practical
      applications of bed modelling techniques, the potential of such techniques in the
      future is discussed. Possible barriers to the adoption of these techniques by
      clinicians are presented together with suggestions about ways of overcoming these
      barriers.

PMID- 11315889
TI  - Detection of gastric cancer by repeat endoscopy within a short time after
      negative examination.
AB  - BACKGROUND AND STUDY AIMS: Although a large number of patients are examined using
      endoscopy in order to identify gastric cancer, it is unclear how individuals
      should be managed after they are not diagnosed as having gastric cancer at the
      time of their initial examinations. This study was conducted to identify the
      group at high risk for gastric cancer who should be examined by repeat endoscopy
      within a short time after obtaining negative results. PATIENTS AND METHODS: The
      study involved 3672 patients who were not diagnosed as having gastric cancer by
      endoscopy in 1993, but underwent re-examination by gastroscopy between January
      1994 and December 1996. RESULTS: Among these participants, 32 patients (0.9%)
      were diagnosed as having gastric cancer. The incidence of gastric cancer was 2.0%
      in participants aged 60 to 69 and 2.7% in those with marked atrophy of the
      gastric mucosa. Multivariate analysis showed that the odds ratios (OR) for
      patients aged 60 to 69 and those with marked atrophy of the gastric mucosa were
      3.092 and 3.255 (P < 0.01), respectively. Gastric cancer was detected in 17.2 %
      of patients who were previously diagnosed as having gastric adenoma and in 2.2%
      of those who were previously diagnosed as having gastric ulcer. The ORs for
      participants with these gastric lesions detected by the initial examination were
      49.417 and 5.259 (P < 0.01), respectively. CONCLUSIONS: Groups at high risk for
      gastric cancer were identified by the initial endoscopy, when two findings
      (gastric lesions, atrophy) and age were combined. We emphasize the importance of
      repeat endoscopic examination for patients who are aged 60 to 69 or have marked
      atrophy of gastric mucosa, even if no lesions are detected on initial endoscopy.
      If gastric adenoma or ulcer are detected, endoscopic examination should be
      likewise repeated or these lesions should be treated by endoscopy or by other
      means.

PMID- 11315890
TI  - Assessment of colorectal lesions using magnifying colonoscopy and mucosal dye
      spraying: can significant lesions be distinguished?
AB  - BACKGROUND AND STUDY AIMS: Assessing the nature of lesions at the time of
      colonoscopy is important, and magnifying colonoscopy allows examination of
      mucosal crypt patterns. In this study, we assessed mucosal crypt patterns to see
      whether we could predict the histological findings. PATIENTS AND METHODS: This
      retrospective study of total colonoscopy using magnifying colonoscopy involved
      4445 patients between December 1993 and July 1998 at the National Cancer Center
      Hospital East. The mucosal crypt patterns of 3438 lesions were observed under
      magnifying colonoscopy with 0.2% indigo carmine solution, and classified
      according to a modified Kudo classification (type I to V). After endoscopic or
      surgical resection (3291 cases and 147 cases, respectively), histopathological
      examination was performed. RESULTS: The diagnostic accuracy of magnifying
      endoscopy for non-neoplastic lesions was 75% (117/157), for adenomatous polyps it
      was 94% (3006/3186), and for invasive carcinomas it was 85 % (81/95).
      CONCLUSIONS: The combination of magnifying colonoscopy and dye spraying is
      helpful in determining the nature of colonic lesions as non-neoplastic, adenomas,
      or invasive carcinomas. Therefore it may be possible to determine, at the time of
      colonoscopy, which lesions require no treatment, which can be removed
      endoscopically, and which should be removed by surgery.

PMID- 11315891
TI  - A prospective controlled trial of an ultrathin versus a conventional endoscope in
      unsedated upper gastrointestinal endoscopy.
AB  - BACKGROUND AND STUDY AIMS: Upper gastrointestinal endoscopy is performed without
      sedation in many countries. Unsedated patients experience more discomfort during
      endoscopy than sedated patients, but few studies have examined factors which
      could be modified to minimize discomfort during the procedure. We assessed the
      effect of endoscope diameter on patient discomfort during unsedated transoral
      gastroscopy. PATIENTS AND METHODS: A total of 322 patients attending for
      unsedated endoscopy were examined using an endoscope of diameter either 6.0 mm or
      9.8 mm. Patients completed a two-part questionnaire assessing tolerance of the
      procedure and discomfort during it. RESULTS: There was failure to complete the
      initial unsedated endoscopy in three of 163 patients in the 6.0 mm group and 14
      of 159 in the 9.8 mm group (P = 0.009). Patients in the 6.0 mm group reported
      less discomfort both during endoscope insertion (P < 0.0001) and during the
      remainder of the procedure (P < 0.0001). 14% of patients in the 6.0 mm group
      indicated that they would request sedation if a further endoscopy were necessary,
      compared with 31% in the 9.8 mm group (P = 0.0005). CONCLUSIONS: Ultrathin
      endoscopes may have a role in clinical practice if randomized comparative studies
      with standard-bore instruments confirm that they do not compromise diagnostic
      quality.

PMID- 11315892
TI  - Endoscopic treatment of postsurgical external pancreatic fistulas.
AB  - BACKGROUND AND STUDY AIMS: External pancreatic fistulas (EPFs) are managed
      primarily by conservative treatment with a success rate of 40-90%. Failures of
      conservative therapy have traditionally been dealt with using surgery; however,
      major morbidity and mortality are associated with operative treatment. The aim of
      this study was to evaluate the feasibility and effectiveness of endoscopic
      treatment in the closure of EPF. PATIENTS AND METHODS: A total of 16 consecutive
      patients with EPF (12 men, four women; median age 50, range 21-66) underwent an
      attempt at endoscopic management after failure of conservative therapy. Four
      patients had chronic pancreatitis. All patients had EPFs occurring after open
      abdominal surgery. The mean interval between the onset of the fistula and our
      intervention was 108 days (range 27-365 days). The mean output volume of the
      fistula was 205 ml/d (range 50-600 ml/ d). The aim of treatment was to lower the
      pancreatic duct pressure and to bypass the ductal disruption by placement of
      drains and/or stents to induce fistula healing. RESULTS: In all, 13 biliary and
      nine pancreatic sphincterotomies were performed in order to gain access to the
      pancreatic duct. Access through the minor papilla was required in one patient.
      Complete visualization of the main pancreatic duct as well as of the fistulous
      tract was obtained in 12 patients (75%). Treatment consisted of placement of a
      nasal pancreatic drain (NPD) across the pancreaticojejunal anastomosis in one
      patient after duodenopancreatectomy. In 11 of the remaining 15 patients (73%) a
      NPD could be placed in the pancreatic duct across the ductal leakage (n = 9) or
      nearby (n = 2). One patient died 24 hours after endoscopic treatment from severe
      sepsis and massive pulmonary embolism. Endoscopic drainage was effective in
      healing the EPF in all patients in whom NPDs had been successfully placed, except
      one. The fistula in this patient healed completely after insertion of an 8.5-Fr
      pancreatic stent. The mean interval between endoscopic treatment and fistula
      closure was 8.8 days (range 2-33 days). No complications related to the
      endoscopic treatment were recorded in this series. In the 12 successfully treated
      patients, fistulas did not recur in any of the 11 surviving patients after a mean
      follow-up of 24.7 months (range 3-63 months). CONCLUSIONS: Endoscopic pancreatic
      drainage, when feasible, is safe and effective for EPF and should be considered
      as a first-line therapy when EPFs do not respond to conservative therapy.

PMID- 11315893
TI  - Topical application of nitrates onto the papilla of Vater: manometric and
      clinical results.
AB  - BACKGROUND AND STUDY AIMS: Systemic administration of nitrates inhibits motility
      of the sphincter of Oddi (SO) but is hampered by a decrease of the arterial blood
      pressure. We evaluate whether topical application of glyceril trinitrate (GTN)
      onto the papilla can facilitate cannulation of the common bile duct during
      routine endoscopic retrograde cholangiopancreatography (ERCP) and compare the
      effect of topical GTN with that of isosorbide dinitrate (ISDN) on SO motility.
      PATIENTS AND METHODS: A total of 80 patients undergoing routine ERCP for
      suspected biliary obstruction received topical application of either saline (n =
      40) or 10 mg of GTN (n = 40) onto the papilla of Vater in a randomized, double
      blind fashion. Thereafter, selective bile-duct cannulation was attempted with a
      0.035" hydrophilic guide wire. In another trial, 16 biliary type III patients
      underwent endoscopic SO-manometry and received in a randomized fashion either 10
      mg of GTN (n = 8) or 10 mg of ISDN (n = 8) which was infused topically onto the
      papilla via the manometric catheter. Thereafter, the manometric recording was
      continued for a further 5 minutes. RESULTS: A spontaneous opening of the papilla
      with concurrent transpapillary bile flow was observed in 24/40 patients after
      topical GTN, and in only 8/40 patients after topical saline (P < 0.01). However,
      neither the number of cannulation attempts nor the time until successful
      cannulation differed significantly between the groups. In addition, the pre-cut
      rate was nearly identical in the two groups. Topical GTN showed no significant
      influence on the mean arterial blood pressure. The SO-baseline pressure was
      significantly lowered by topical GTN (28.2+/-12.9 mm Hg before ISDN vs. 22.5+/
      13.7 mmHg after P<0.01). The phasic SO motility was also strongly inhibited by
      both drugs. However, the effect of GTN completely wanes after 3 minutes, whereas
      ISDN inhibited SO motility for > 5 minutes in all patients. CONCLUSIONS: Both
      topically administered GTN and ISDN evoked a profound inhibition of SO motility,
      but the effect of ISDN was longer lasting than that of GTN. However, locally
      administered GTN did not facilitate selective bile-duct access during routine
      ERCP.

PMID- 11315894
TI  - Balloon dilation is preferable to bougienage in children with esophageal atresia.
AB  - BACKGROUND AND STUDY AIMS: Esophageal strictures are a common problem after
      surgical repair in children with esophageal atresia. The traditional procedure in
      these patients is dilation using bougie dilators, usually controlled
      fluoroscopically or endoscopically. Nowadays, an alternative technique is balloon
      catheter dilation. The aim of this study was to report our experience with
      pneumatic balloon dilation and to compare this method with previously performed
      bougienage with regard to efficacy. PATIENTS AND METHODS: Over 16 years, 34
      patients who developed symptomatic strictures were encountered at our
      institution. In the first 9 years 12 patients underwent 178 bougienages (group
      C). In the last 7 years six patients who had undergone 202 previous bougienages
      (group B), and 16 patients who had undergone no bougienages (group A), underwent
      52 dilations. The dilation was carried out under intravenous sedation using a
      combination of midazolam and etomidate. The balloon was placed in the stricture
      endoscopically and the procedure was performed under fluoroscopic and endoscopic
      control. RESULTS: In all patients the dilation was effective and involved minimal
      trauma. The strictures required 1 to 7 procedures (median 2) over a maximum of 18
      months (median 3 months) for a good treatment result. The complications observed
      were two perforations, one of them with pneumothorax (both treated
      conservatively), and two compressions of the trachea (interruption of the
      procedure, but efficient dilation was eventually achieved). The method was more
      effective than bougienage (1 to 60 bougienages were required per patient, median
      9). CONCLUSIONS: Compared with traditional bougienage, balloon dilation of
      esophageal strictures is less traumatic and more effective. Complications are
      rare and can be managed conservatively. In our opinion this procedure is the
      appropriate treatment for strictures, even in very small infants, after repair of
      esophageal atresia.

PMID- 11315895
TI  - Diagnostic duodenal bulb biopsy in celiac disease.
AB  - BACKGROUND AND STUDY AIMS: Duodenal or jejunal biopsies are needed to establish
      the diagnosis of celiac disease. It is widely advocated that these biopsies be
      taken from the distal duodenum. PATIENTS AND METHODS: After finding two index
      cases with diagnostic biopsies taken from the duodenal bulb, we retrospectively
      analyzed biopsies from the descending duodenum and the duodenal bulb of 51
      patients with suspected or diagnosed celiac disease. The diagnosis of celiac
      disease and classification of the histological changes were performed by one
      pathologist. RESULTS: In the two index cases the diagnosis of celiac disease
      could only be established by taking the biopsies from the duodenal bulb, and not
      from the descending duodenum. In the retrospective analysis the number of
      intraepithelial lymphocytes was on average higher, but not significantly, in the
      descending part of the duodenum. CONCLUSIONS: Most patients with celiac disease
      show similar mucosal changes in biopsies taken from the descending part of the
      duodenum and from the duodenal bulb. But in patients who have already been on a
      gluten-free diet in childhood and later abandoned their diet, an additional
      duodenal bulb biopsy should be done.

PMID- 11315896
TI  - Surgical trainees' attitudes to laparoscopic cholecystectomy: a regional survey.
AB  - BACKGROUND AND STUDY AIMS: Since the introduction of laparoscopic cholecystectomy
      (LC), numerous articles have been written emphasising its many advantages over
      open cholecystectomy (OC). However, reports also highlight increased
      complications following LC such as bile-duct, vascular and bowel injuries. We
      aimed to study surgical trainees as a defined population of individuals who, with
      increasing exposure to cholecystectomy, would become fully aware of LC's
      advantages and controversies. We wished to test the hypothesis that, with
      increasing in-depth knowledge, they might opt for OC rather than LC if they
      themselves required cholecystectomy. MATERIALS AND METHODS: We conducted a postal
      survey of all 133 Northern Ireland surgical trainees identified as having
      exposure to LC during their training. Trainees were asked whether they would
      undergo LC and if so with which preconditions. Similarly, if they stated a
      preference for open cholecystectomy they were asked to state the reason. A
      minimum time period of 18 months was considered adequate for trainees to become
      relatively more experienced in this field compared with their more junior
      counterparts. RESULTS: A response rate of 80.5% (107/133) was achieved. A total
      of 51 of 107 trainees had at least 18 months' experience. Of the 107 who replied,
      88.8% (95/107) would be willing to undergo LC. A total of 12 of 107 trainees
      would opt for OC, with twice as many experienced trainees (8 vs. 4) opting for
      this approach (n.s. [not significant]). Significantly more experienced trainees
      cited the use of laparoscopic cholangiography as a precondition for LC compared
      with their inexperienced counterparts (7 vs. 1, p = 0.020). Of 107 trainees, 19
      would request use of the open first port (Hasson) technique; 14 of these had at
      least 18 months' experience (p = 0.009). CONCLUSION: Our survey confirms that the
      majority of trainees would be willing to undergo LC. However, increased
      experience of LC may alter an individual's expectations about how LC should
      ideally be performed.

PMID- 11315897
TI  - Endoscopic therapy of benign tumors of the papilla of Vater.
AB  - BACKGROUND AND STUDY AIMS: The aim of this study was to evaluate the technical
      feasibility and safety of endoscopic treatment in 16 patients with benign
      adenomas of the papilla of Vater. PATIENTS AND METHODS: This study involved 16
      patients with confirmed adenoma of the papilla of Vater. Diagnosis of adenoma was
      made by endoscopic findings, benign histologic findings at forceps and snare
      biopsy, and endoscopic ultrasonography (EUS). The size of the tumor ranged from 2
      to 7 cm. Papillectomy by diathermy snare consisted of excision of the adenoma
      together with the papilla of Vater. In three patients, residual tissue that could
      not be removed with the snare was removed using argon coagulation. RESULTS:
      Postpapillectomy complications included bleeding in two patients. Two patients
      had acute pancreatitis. No procedure-related death occurred. Follow-up
      duodenoscopy was performed at 6 and 12 months after papillectomy and yearly
      thereafter. Three patients had recurrences (benign adenoma in all cases). Two
      patients were treated endoscopically. One patient with extension of tumor into
      the distal common bile duct was referred to surgery. CONCLUSIONS: Endoscopic
      resection of adenomas of the papilla of Vater appears to be a viable alternative
      to surgical therapy, particularly in patients for whom surgery is a high-risk
      approach.

PMID- 11315898
TI  - Endoscopy and early neoplasia: better but not the best.

PMID- 11315899
TI  - Clinical application of argon plasma coagulation in gastrointestinal endoscopy:
      has the time come to replace the laser?

PMID- 11315900
TI  - Minimally invasive surgery.
AB  - In 1987, Mouret performed the first laparoscopic cholecystectomy - dramatically
      changing the history of surgical practice. No other aspect of surgery has
      developed with such vigor as laparoscopy. Previously, surgeons had attempted to
      define the maximum level of surgical intervention a patient could withstand - but
      as laparoscopic surgery developed, this paradigm was turned on its head.
      Minimally invasive surgeons are continuing to determine and redefine how much can
      be accomplished through smaller incisions and with minimal surgical stress.
      Laparoscopy is still only in its infancy. This article reviews current aspects of
      laparoscopic surgery in 1999-2000 in relation to gallbladder, gastric,
      colorectal, and splenic disease, as well as reviewing the current role of
      laparoscopic surgery in the treatment of abdominal wall hernias.

PMID- 11315901
TI  - Pit pattern in colorectal neoplasia: endoscopic magnifying view.

PMID- 11315902
TI  - Idiopathic submucosal hematoma of esophagus complicated by dissecting aneurysm,
      followed-up endoscopically during conservative treatment.
AB  - Submucosal hematoma of the esophagus is encountered as a rare complication of
      endoscopic treatment for esophageal varices, but is seen more often with the
      increasing frequency of endoscopic applications. Idiopathic submucosal hematoma
      is a rarer event and in most cases sudden intense vomiting has been postulated as
      its cause. We report here the case of such a patient whose condition was
      complicated by a dissecting aneurysm. During conservative treatment, careful
      follow-up was required to differentiate the submucosal hematoma from an aorto
      esophageal fistula.

PMID- 11315903
TI  - Endoscopic and radiological features of intramural esophageal dissection.
AB  - A 41-year-old woman was admitted to our hospital complaining of chest pain,
      dysphagia, and odynophagia after an upper respiratory tract infection and
      nasogastric tube insertion. An upper endoscopy showed a large submucosal bulge
      along the posterior wall from the upper esophagus with mucosal tears and bridge
      formation, extending down to the lower esophagus. A barium esophagogram revealed
      a "double-barreled" esophagus, and chest computed tomography (CT) scan showed
      eccentric thickening of the esophageal wall. The diagnosis of intramural
      esophageal dissection (IED) was made and the patient was managed conservatively
      with nothing by mouth and intravenous hydration. The clinical course was
      uneventful; the patient was discharged later and up to the time of writing has
      been completely asymptomatic, with normal swallowing function.

PMID- 11315904
TI  - Endoscopic retrograde cholangiopancreatography and acute biliary pancreatitis:
      time for a divorce?

PMID- 11315905
TI  - Severe gallstone pancreatitis.

PMID- 11315906
TI  - A case of Cronkhite-Canada syndrome involving the entire gastrointestinal tract.

PMID- 11315907
TI  - A biopsy-negative esophageal cancer: diagnosis by combination of bite biopsy and
      endoscopic mucosal resection using a cap-fitted panendoscope (EMRC).

PMID- 11315908
TI  - Silent free perforation of duodenal ulcer in an elderly patient presenting with
      melena: management directed by upper endoscopy and percussion of the liver.

PMID- 11315909
TI  - Subtrocar for removing a gallbladder from the abdominal cavity.

PMID- 11315910
TI  - Images in focus laparoscopic findings in Wilson's disease without cirrhosis.

PMID- 11315911
TI  - Images in focus uneventful endoscopic retrieval of a cannibalized aortic trouser
      graft.

PMID- 11315912
TI  - Human receptors for immunoglobulin G: key elements in the pathogenesis of
      rheumatic disease.
AB  - The structural diversity of Fc gammaR provides a mechanism by which IgG can
      elicit a broad range of cell responses. Fc gammaR vary in their affinity for IgG,
      their preference for IgG subclasses, the cell types in which they are expressed,
      and the intracellular signals which they elicit--stimulatory or inhibitory.
      Expansion in our knowledge of structure-function relationships among Fc gammaR
      has identified them as heritable risk factors for disease susceptibility and
      valuable targets for therapeutic modulation of the immune system.

PMID- 11315913
TI  - Does pain in fibromyalgia reflect somatization?

PMID- 11315914
TI  - High-dose chemotherapy and autologous hematopoietic stem cell transplantation in
      patients with rheumatoid arthritis: results of an open study to assess
      feasibility, safety, and efficacy.
AB  - OBJECTIVE: To assess the feasibility, safety, and efficacy of high-dose
      chemotherapy and autologous hematopoietic stem cell transplantation (HSCT) in
      patients with severe, refractory rheumatoid arthritis (RA). METHODS: Fourteen
      patients (3 male, 11 female, mean age 43 years, mean disease duration 10 years)
      with active, destructive, refractory RA entered the study. Autologous
      hematopoietic stem cells were collected by leukapheresis after mobilization with
      a single infusion of cyclophosphamide (CYC; 4 gm/m2) and subcutaneous injections
      of filgrastim (granulocyte colony-stimulating factor). Immunomagnetic selection
      of CD34+ cells from the leukapheresis products was performed to deplete
      potentially autoreactive lymphocytes. The conditioning regimen consisted of
      intravenous administration of high doses of CYC (cumulative dose 200 mg/kg), with
      subsequent reinfusion of the graft. Patients were monitored for disease activity,
      disability, adverse effects, and hematopoietic and immunologic reconstitution.
      RESULTS: All 14 patients completed the mobilization and leukapheresis procedures
      successfully, and 12 proceeded to receive conditioning and transplantation.
      Engraftment occurred in all of these patients, with rapid hematologic recovery.
      No major unexpected toxicity was observed. Marked improvement of disease activity
      was recorded in 8 of 12 patients at >50% of the visits, with a followup ranging
      from 7 months to 21 months. The clinical responders included 2 patients who had
      previously failed treatment with tumor necrosis factor (TNF) blocking agents.
      CONCLUSION: High-dose chemotherapy followed by autologous HSCT is feasible and
      safe, and can result in long-term improvement of disease activity in patients
      whose condition previously did not respond to conventional antirheumatic drugs or
      TNF blocking agents. The persistence of active disease in some patients may
      reflect the heterogeneity of the underlying disease process.

PMID- 11315915
TI  - The stress protein BiP is overexpressed and is a major B and T cell target in
      rheumatoid arthritis.
AB  - OBJECTIVE: The ubiquitously expressed intracellular protein formerly designated
      p68 has been identified as autoantigen at both the antibody and the T cell level
      in rheumatoid arthritis (RA). METHODS: We used 2 independent approaches, Edman
      degradation and matrix-assisted laser desorption ionization-time-of-flight mass
      spectrometry, to characterize p68, and we compared its features with those of the
      endoplasmic reticulum stress protein BiP. RESULTS: In synovial sections from RA
      patients, BiP was highly overexpressed as compared with control sections. Under
      in vitro stress conditions, BiP was found to translocate to the nucleus and the
      cell surface. BiP-specific autoantibodies were present in 63% of 400 RA patients,
      in 7% of 200 patients with other rheumatic diseases, and in none of the healthy
      subjects. Thus, BiP-specific autoantibodies represent a new diagnostic marker in
      RA. Furthermore, we found that BiP-specific T cell reactivity was altered in RA.
      In healthy individuals and patients with other rheumatic diseases, BiP-reactive T
      cells were undetectable. In RA, overt T cell reactivity to BiP was observed or
      could be induced by specifically blocking antigen presentation to potentially
      regulatory T cells. CONCLUSION: Since overexpression of BiP has been shown to
      decrease the sensitivity of cells to killing by cytotoxic T cells, BiP
      overexpression and BiP-specific autoimmunity may be involved in the pathogenesis
      of RA.

PMID- 11315916
TI  - Blockade of Wnt-5A/frizzled 5 signaling inhibits rheumatoid synoviocyte
      activation.
AB  - OBJECTIVE: It is not understood why cultured fibroblast-like synoviocytes (FLS)
      from patients with rheumatoid arthritis (RA) often display a persistently
      activated phenotype, despite removal from an inflammatory environment.
      Previously, we found that these FLS expressed high levels of both Wnt-5A and
      Frizzled 5 (Fz5), a receptor-ligand pair implicated in both limb bud and bone
      marrow stem cell development. The objective of the present experiments was to
      determine whether Wnt-5A/FzS signaling contributes to FLS activation. METHODS:
      Wnt-5A expression in FLS was inhibited by transfection with both antisense and
      dominant negative (dn) vectors. Fz5 signaling was blocked with an antibody to the
      extracellular domain of the receptor. The effects of these treatments on the
      expression of the proinflammatory cytokines interleukin-6 (IL-6) and IL-15 and on
      the expression of receptor activator of nuclear factor kappaB ligand (RANKL) were
      assessed by reverse transcriptase-polymerase chain reaction and immunoblotting.
      RESULTS: Both antisense Wnt-5A and dnWnt-5A vectors, but not empty vector,
      diminished IL-6 and IL-15 expression in RA FLS. Anti-Fz5 antibody exerted similar
      effects and also reduced RANKL expression. CONCLUSION: Wnt-5A/Fz5 signaling may
      contribute to the activated state of FLS in RA. Receptor antagonists of Fz5
      should be considered for the treatment of refractory synovitis.

PMID- 11315917
TI  - Involvement of the nuclear orphan receptor NURR1 in the regulation of
      corticotropin-releasing hormone expression and actions in human inflammatory
      arthritis.
AB  - OBJECTIVE: To examine the regulation and mode of action of peripheral
      corticotropin-releasing hormone (CRH) in human inflammatory arthritis. METHODS:
      CRH messenger RNA (mRNA) levels were measured in normal and inflamed synovial
      tissue and in primary synoviocytes prior to and following cytokine stimulation.
      Primary synoviocytes were transiently transfected with CRH promoter/reporter
      constructs, and promoter activity in response to cytokines was assessed.
      Immunohistochemical staining established CRH receptor expression, and Northern
      blot analysis confirmed that the nuclear transcription factors NUR77 and NURR1
      contributed to synovial CRH receptor-mediated signaling. Primary synoviocytes
      were treated with pro- and antiinflammatory mediators, and the time course of
      NURR1 and NUR77 modulation was examined. Nuclear extracts were analyzed by
      electrophoretic mobility shift assay to determine NURR1 binding to the CRH
      promoter/enhancer. RESULTS: CRH mRNA was up-regulated in the synovial tissue in
      rheumatoid arthritis (RA), psoriatic arthritis (PsA), and sarcoid arthritis, but
      not in normal synovium. Inflammatory cytokines, such as interleukin-1beta and
      tumor necrosis factor alpha, enhanced the transcriptional activity of the human
      CRH promoter and increased levels of CRH mRNA in primary synoviocytes. Synovial
      CRH functioned in a paracrine manner to induce NURR1 and NUR77. NURR1 was
      abundantly expressed in the inflammatory cells of both RA and PsA synovium. NURR1
      and NUR77 were differentially regulated, and NURR1 was the major cytokine
      regulated member of the NURR subfamily as well as the mediator of cytokine- and
      CRH-dependent inflammatory responses in synovium. Furthermore, glucocorticoids
      dramatically suppressed cytokine- and CRH-induced synovial NURR1 mRNA.
      CONCLUSION: These data demonstrate the involvement of the transcription factor
      NURR1 in the regulation of CRH expression and activity in human inflammatory
      arthritis.

PMID- 11315918
TI  - Expression of angiogenic factors in juvenile rheumatoid arthritis: correlation
      with revascularization of human synovium engrafted into SCID mice.
AB  - OBJECTIVE: Although increased vascularity was noted in early histopathologic
      studies of juvenile rheumatoid arthritis (JRA) synovium, the available data on
      angiogenesis in JRA are very limited. The main purposes of this study were to
      assess expression of the key angiogenic factors in JRA synovium, and to evaluate
      a SCID mouse model of JRA as an approach to study in vivo regulation of the
      expression of these factors in JRA. METHODS: RNase protection assay was used to
      assess the expression of the key angiogenic factors in fresh JRA synovium and in
      JRA synovial tissue fragments that had been minced and then implanted into SCID
      mice. Vascularity of the samples was assessed by immunohistochemical staining for
      von Willebrand factor. Synovial specimens obtained from patients with
      osteoarthritis (OA) or other noninflammatory arthropathies were used as controls.
      RESULTS: Detectable levels of messenger RNA for vascular endothelial growth
      factor and angiopoietin 1 and their respective receptors, as well as endoglin and
      thrombin receptors, were present in all JRA tissue specimens studied. The levels
      of expression of these factors in JRA tissues were significantly higher than
      those in tissues obtained from patients with OA or other noninflammatory
      arthropathies. Furthermore, increased expression of the key angiogenic factors in
      the fresh JRA tissues correlated with the exuberant revascularization of JRA
      minced tissue fragments implanted into SCID mice. This was in sharp contrast to
      the poor revascularization of implanted OA tissues. CONCLUSION: JRA synovium is
      characterized by high angiogenic activity. SCID mouse-human JRA synovium chimeras
      may provide a good approach to study the in vivo regulation of angiogenesis in
      JRA.

PMID- 11315919
TI  - Cytokine gene polymorphisms and susceptibility to juvenile idiopathic arthritis.
      British Paediatric Rheumatology Study Group.
AB  - OBJECTIVE: To investigate the involvement of candidate cytokine genes in the
      pathogenesis of juvenile idiopathic arthritis (JIA). METHODS: Single nucleotide
      polymorphisms and intragenic microsatellite markers within 8 candidate cytokine
      genes (interleukin-1alpha [IL-1alpha], IL-2, IL-4, IL-6, IL-10, interferon-alpha1
      [IFNA1], interferon-gamma [IFNG], and interferon regulatory factor 1 [IRF-1])
      were investigated in 417 Caucasian patients with clinically characterized JIA and
      a panel of 276 unrelated, healthy Caucasian controls, all from the United
      Kingdom. RESULTS: A novel 3'-untranslated region (3'UTR) polymorphism in IRF-1
      was found to be associated with susceptibility to JIA (corrected P = 0.002). No
      significant association with IL-1alpha, IL-2, IL-4, IL-6, IL-10, IFNA1, or IFNG
      was observed. CONCLUSION: An association between JIA and a previously unreported
      3'UTR polymorphism of IRF-1 was observed. This association was not found to be
      specific to any particular JIA subgroup. This suggests that IRF-1 may contribute
      to a common pathogenesis shared by all JIA patients, regardless of clinical
      phenotype. This is most likely to be a genetic contribution to the chronic
      inflammatory process that underlies JIA pathology.

PMID- 11315920
TI  - The effect of estrogen plus progestin on knee symptoms and related disability in
      postmenopausal women: The Heart and Estrogen/Progestin Replacement Study, a
      randomized, double-blind, placebo-controlled trial.
AB  - OBJECTIVE: Most observational studies suggest that postmenopausal women taking
      hormone replacement therapy have a reduced risk of radiographic knee and hip
      osteoarthritis (OA). There are no randomized trial data on the association of
      hormone treatment with knee or hip OA, and no studies have been published
      regarding the relationship of hormone treatment to knee or hip symptoms. This
      study examined the association of hormone treatment with prevalent knee symptoms
      and disability related to knee pain as assessed at the final visit of the Heart
      and Estrogen/Progestin Replacement Study (HERS). METHODS: The HERS was a 4-year
      randomized, double-blind, placebo-controlled trial of estrogen plus medroxy
      progesterone acetate for prevention of coronary heart disease in postmenopausal
      women with documented coronary disease. Participants in this substudy on knee
      pain were 969 postmenopausal women, with a mean age of 66 years and mean body
      mass index of 28.6 kg/m2, attending the final visit at 9 clinical centers.
      Frequent knee symptoms were assessed by interview and the severity of knee pain
      and disability related to knee pain were determined using the Western Ontario and
      McMaster Universities Osteoarthritis Index (WOMAC). Knee symptoms and disability
      were compared between women assigned to receive hormones and those assigned to
      receive placebo. RESULTS: Frequent knee pain was reported in 24.1% of women
      assigned to receive hormone therapy versus 26.1% of those assigned to the placebo
      group, a difference of -2.0% (95% confidence interval [95% CI] -7.4% to 3.5%).
      Among women with knee pain, there were no differences in the severity of pain
      (score difference -0.2, 95% CI -1.2 to 0.8) or disability (score difference -0.7,
      95% CI -3.8 to 2.4) as assessed on the WOMAC. All results were similar for women
      whose body mass index was either above or below the median. CONCLUSION: In a
      group of older, postmenopausal women with cardiac disease, we found no
      significant effect of 4 years of estrogen plus progestin therapy compared with
      placebo on knee pain and related disability. Our findings may not apply to other
      groups of women or to the effect of hormone therapy on the structural changes of
      knee OA.

PMID- 11315921
TI  - Acupuncture for osteoarthritis of the knee: a systematic review.
AB  - OBJECTIVE: To evaluate trials of acupuncture for osteoarthritis (OA) of the knee,
      to assess the methodologic quality of the trials and determine whether low
      quality trials are associated with positive outcomes, to document adverse
      effects, to identify patient or treatment characteristics associated with
      positive response, and to identify areas of future research. METHODS: Eight
      databases and 62 conference abstract series were searched. Randomized or quasi
      randomized trials of all languages were included and evaluated for methodologic
      quality using the Jadad scale. Outcomes were pain, function, global improvement,
      and imaging. Data could not be pooled; therefore, a best-evidence synthesis was
      performed to determine the strength of evidence by control group. The adequacy of
      the acupuncture procedure was assessed by 2 acupuncturists trained in treating OA
      and blinded to study results. RESULTS: Seven trials representing 393 patients
      with knee OA were identified. For pain and function, there was limited evidence
      that acupuncture is more effective than being on a waiting list for treatment or
      having treatment as usual. For pain, there was strong evidence that real
      acupuncture is more effective than sham acupuncture; however, for function, there
      was inconclusive evidence that real acupuncture is more effective than sham
      acupuncture. There was insufficient evidence to determine whether the efficacy of
      acupuncture is similar to that of other treatments. CONCLUSION: The existing
      evidence suggests that acupuncture may play a role in the treatment of knee OA.
      Future research should define an optimal acupuncture treatment, measure quality
      of life, and assess acupuncture combined with other modalities.

PMID- 11315922
TI  - Regulation of YKL-40 production by human articular chondrocytes.
AB  - OBJECTIVE: YKL-40 (human cartilage glycoprotein 39) is one of the most abundant
      proteins secreted by cultured chondrocytes. The objectives of the present study
      were to identify regulators of YKL-40 production in cartilage and chondrocytes
      and to map the localization of YKL-40 in chondrocytes. METHODS: Human articular
      chondrocytes and cartilage explants (obtained from subjects at autopsy, from a
      tissue bank, and from osteoarthritis [OA] patients undergoing total joint
      replacement surgery) were stimulated with cytokines, growth factors, and other
      agents. YKL-40 expression was analyzed by Northern blot and polymerase chain
      reaction. YKL-40 secretion into the media was determined by enzyme-linked
      immunosorbent assay. RESULTS: YKL-40 production increased to very high levels
      during the early phase of chondrocyte monolayer culture and in normal cartilage
      explant cultures as a response to tissue injury. Spontaneous YKL-40 release was
      higher in OA than in normal cartilage explant cultures. In chondrocyte monolayer
      cultures, interleukin-1beta (IL-1beta) and transforming growth factor beta
      (TGFbeta) decreased the levels of secreted YKL-40, and this was associated with a
      reduction in YKL-40 messenger RNA levels. IL-1beta, but not TGFbeta, reduced YKL
      40 production in cartilage explant cultures. Media from explants treated with
      cycloheximide had no detectable YKL-40, suggesting that the released protein was
      newly synthesized. Immunofluorescence microscopy showed YKL-40 staining in the
      Golgi system of the chondrocytes, but YKL-40 could not be detected in the
      extracellular matrix. CONCLUSION: The spontaneous increase in the production of
      YKL-40 in the early phase of culture appears to represent a cellular response to
      changes in the extracellular matrix environment. This, coupled with the profound
      suppressive effects of IL-1beta and TGFbeta on YKL-40 production, identifies a
      novel regulatory pattern for this major chondrocyte-derived protein.

PMID- 11315923
TI  - Implication of cartilage intermediate layer protein in cartilage destruction in
      subsets of patients with osteoarthritis and rheumatoid arthritis.
AB  - OBJECTIVE: To investigate whether cartilage intermediate layer protein (CILP), a
      protein recently cloned from human articular cartilage, is recognized as an
      autoantigen in patients with osteoarthritis (OA) and rheumatoid arthritis (RA),
      and whether the immune response against CILP is involved in disease pathogenesis.
      METHODS: Recombinant fusion proteins, which contain the first half (C1), second
      half (C2), or 3 fragments within the C2 region (designated C2F1, C2F2, and C2F3)
      of the non-porcine nucleotide pyrophosphohydrolase-homologous region of CILP,
      were prepared using Escherichia coli. Autoantibodies to these proteins in serum
      samples from patients with OA or RA and from age-matched healthy individuals were
      detected by enzyme-linked immunosorbent assay and Western blotting. In addition,
      mice were immunized with a mixture of the C1 and C2 fusion proteins to assess the
      arthrogenicity of CILP. RESULTS: Production of antibodies to the C2 region was
      detected in 10.5% (11 of 105) of the tested OA patients and in 8.0% (7 of 88) of
      the tested RA patients, although antibodies to the C1 region were rarely detected
      in either patient group. All C2F1, C2F2, and C2F3 fragments were found to carry
      autoepitopes. The C2F2 fusion protein was recognized most frequently in the
      tested OA patients, whereas the C2F3 fusion protein was dominantly recognized in
      the tested RA patients. All 4 mice strains, DBA/1J, ICR, C57BL/6, and BALB/c,
      immunized with the CILP fusion proteins developed chronic arthritis; in
      particular, the ICR mice developed polyarthritis that was characterized by
      infiltration of mononuclear cells in the synovium and exfoliation of the surface
      of cartilage. CONCLUSION: The immune response to CILP may play a role in the
      pathogenesis of inflammatory joint destruction. Our results support the role of
      an immune-mediated process in the joint destruction present in chronic
      arthropathies such as OA and RA. The results suggest that suppression of immune
      responses to various components of the cartilage, such as CILP, might be
      therapeutically beneficial in these chronic arthropathies.

PMID- 11315924
TI  - Imaging of collagen and proteoglycan in cartilage sections using Fourier
      transform infrared spectral imaging.
AB  - OBJECTIVE: To test the hypothesis that Fourier transform infrared (FTIR) spectral
      imaging, coupled with multivariate data processing techniques, can image the
      spatial distribution of matrix constituents in native and engineered cartilage
      samples. METHODS: Tissue sections from native and trypsin-digested bovine nasal
      cartilage (BNC) and from engineered cartilage, generated by chick sternal
      chondrocytes grown in a hollow fiber bioreactor, were placed either on calcium
      fluoride windows for FTIR analysis or gelatinized microscope slides for
      histologic analysis. Based on the assumption that cartilage is predominantly
      chondroitin sulfate (CS) and type II collagen, chemical images were extracted
      from FTIR spectral imaging data sets using 2 multivariate methods: the Euclidean
      distance algorithm and a least-squares approach. RESULTS: Least-squares analysis
      of the FTIR data of native BNC yielded a collagen content of 54 +/- 13% and a CS
      content of 37 +/- 16% (mean +/- SD). Euclidean distance analysis of measurements
      made on trypsin-digested BNC demonstrated only trace amounts of CS. For
      engineered cartilage, the CS content was significantly lower (15 +/- 5%), while
      the collagen content (73 +/- 6%) was significantly higher than biochemically
      determined values (CS 34%, collagen 5%, protein 61%). These differences are due
      to the fact that the dimethylmethylene blue assay overestimated the CS content of
      the tissue because it is not specific for CS, while the FTIR spectral imaging
      technique overestimated the collagen content because it lacks specificity for
      different proteins. CONCLUSION: FTIR spectral imaging combines histology-like
      spatial localization with the quantitative capability of bulk chemical analysis.
      For molecules with a unique spectral signature, such as CS, the FTIR technique
      coupled with multivariate analysis can define a unique spatial distribution.
      However, for some applications, the lack of specificity of this technique for
      different types of proteins may be a limitation.

PMID- 11315925
TI  - Alterations of dendritic cells in systemic lupus erythematosus: phenotypic and
      functional deficiencies.
AB  - OBJECTIVE: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease
      characterized by B cell hyperactivity and defective T cell functions, including
      interleukin-2 production and proliferation. The defects in T cell function may
      result from underlying defects in antigen-presenting cell (APC) function. The
      present study was undertaken to investigate phenotypic and functional
      characteristics of peripheral blood dendritic cells (DC), as the most potent APC,
      in SLE patients in comparison with healthy controls. METHODS: Samples from 25 SLE
      patients and 15 healthy controls were studied. To identify DC, peripheral blood
      mononuclear cells were double stained with monoclonal antibodies against lineage
      marker (lin)-specific molecules CD3, CD19, CD14, and CD16, versus CD4. DC were
      characterized phenotypically by flow cytometry. The stimulatory capacity of DC
      was determined by proliferation of T cells in the mixed lymphocyte reaction
      (MLR), which was assessed by measurement of tritiated thymidine incorporation in
      studies using granulocyte-macrophage colony-stimulating factor-activated, DC
      enriched APC. Correlations between DC counts and phenotype and clinical
      parameters in SLE patients were determined. RESULTS: Lin-, HLA-DR+, CD4+ DC were,
      on average, 50% less frequent in SLE patients than in controls. Moreover, among
      DC, the proportions of B7+ and CD40+ cells were reduced and, in particular, the
      CD11c+ subset was reduced by an average of 80% in SLE patients. Functional
      analysis of DC-enriched APC from SLE patients revealed a diminished T cell
      stimulatory capacity in both the allogeneic and the antigen-specific MLR, as
      compared with healthy individuals. Although the frequencies of DC were weakly
      inversely correlated with disease activity and/or current treatment protocols,
      our data suggest a disease-intrinsic defect. CONCLUSION: The considerable
      alterations of DC and DC subsets in SLE patients may contribute to the pathogenic
      mechanisms involved in the disease.

PMID- 11315926
TI  - Biologic activity and plasma clearance of prolactin-IgG complex in patients with
      systemic lupus erythematosus.
AB  - OBJECTIVE: To characterize the clinical findings in hyperprolactinemic systemic
      lupus erythematosus (SLE) patients with or without macroprolactinemia (big, big
      prolactin [PRL]) due to anti-PRL autoantibodies (PRL-IgG complex), and to assess
      the bioactivity and structure of big, big PRL. METHODS: Twenty-seven SLE patients
      with hyperprolactinemia (HPRL) were studied. Patients with (n = 8) or without (n
      = 19) big, big PRL were identified by gel filtration chromatography and affinity
      chromatography for IgG. PRL concentrations in serum and fractions by gel
      filtration chromatography and affinity chromatography were characterized by
      immunoradiometric assay (IRMA), Nb2 bioassay, sodium dodecyl sulfate
      polyacrylamide gel electrophoresis and Western blotting, and clearance studies.
      RESULTS: SLE patients without big, big PRL had significantly higher levels of
      disease activity, cause-proven HPRL, and menstrual disturbances compared with
      patients with big, big PRL (P < or = 0.05). The big, big PRL fractions by Western
      blotting revealed a single 23-kd nonglycosylated PRL. The Nb2:IRMA ratio of the
      samples with big, big PRL was significantly higher than that of the samples
      without big, big PRL (P < or = 0.02). However, bioactivity of big, big PRL in the
      Nb2 cells was very similar to that of 23-kd nonglycosylated PRL. Clearance
      studies in rats demonstrated that the PRL-IgG complex was eliminated more slowly
      than monomeric PRL (little PRL). CONCLUSION: We demonstrated that the PRL-IgG
      complex was formed by 23-kd nonglycosylated PRL that was noncovalently bound to
      IgG and showed that the complex was fully active in vitro. This result suggests
      that the absence of symptoms of HPRL or lower levels of lupus activity in these
      patients is not explained by lower bioactivity of the complex. Instead, because
      of the large molecular size of the complex, the PRL does not easily cross the
      capillary walls. Delayed clearance of the PRL-IgG complex may account for
      increased serum levels of PRL in SLE patients with anti-PRL autoantibodies.

PMID- 11315927
TI  - Identification of an Fc gamma receptor-independent mechanism by which intravenous
      immunoglobulin ameliorates antiphospholipid antibody-induced thrombogenic
      phenotype.
AB  - OBJECTIVE: Patients with the antiphospholipid antibody syndrome (APS) often
      experience recurrent arterial and venous thrombosis and pregnancy losses.
      Intravenous immunoglobulin (IVIG) therapy has prevented pregnancy loss in some
      women with APS and has reversed fetal resorption rates in murine models of
      pregnancy loss. Although the basis for these effects is unknown, effector
      mechanisms of pathogenic antibodies often involve receptors for IgG (Fc gamma
      receptors [Fc gammaR]). We examined the potential mechanisms of action of WIG in
      an in vivo murine model of antiphospholipid antibody (aPL)-induced thrombosis and
      endothelial cell activation. METHODS: Mice infused with IgG containing human
      anticardiolipin antibodies (aCL) were treated with IVIG (36 microg i.v.), saline,
      or ovalbumin. Surgically induced thrombus formation and in vivo leukocyte
      adhesion to endothelial cells were measured. Circulating levels of aCL were
      measured by enzyme-linked immunosorbent assay. To determine whether Fc gammaR are
      required for the effects of IVIG, we treated mice deficient in stimulatory Fc
      gammaR. To examine the effects of IVIG on endogenously generated antibody, we
      treated mice immunized with beta2-glycoprotein I (beta2GPI). RESULTS: IVIG
      treatment inhibited aPL-induced endothelial cell activation and enhancement of
      thrombosis in mice passively infused with human aPL-containing IgG, and this was
      associated with a decrease in aPL levels. Similarly, IVIG lowered aPL levels and
      inhibited thrombogenesis in mice immunized with beta2GPI. The thrombophilic
      effects of aPL were evident in Fc gammaR-deficient mice. CONCLUSION: Treatment
      with IVIG inhibits the thrombogenic effects of aPL in vivo and reduces the levels
      of aCL in the circulation. Blockade of stimulatory Fc gammaR on inflammatory
      cells is not necessary for this effect. The mechanism of action of IVIG is more
      likely saturation of the IgG transport receptor, leading to accelerated
      catabolism of pathogenic aPL. These results have implications in the management
      of thrombosis in APS and may have applications for pregnant patients with a
      history of APS.

PMID- 11315928
TI  - A novel role for interleukin-18 in human natural killer cell death: high serum
      levels and low natural killer cell numbers in patients with systemic autoimmune
      diseases.
AB  - OBJECTIVE: Patients with systemic autoimmune diseases have been reported to have
      reduced numbers of peripheral blood natural killer (NK) cells compared with
      healthy subjects. The ability of selected cytokines to trigger NK cell death
      prompted us to compare the levels of peripheral blood cytokines with the numbers
      of NK cells in patients with various systemic autoimmune diseases. METHODS: We
      used enzyme-linked immunosorbent assays to measure the concentration of selected
      cytokines (interleukin-18 [IL-18], IL-15, IL-12, IL-2, interferon-gamma
      [IFNgamma], and tumor necrosis factor alpha [TNFalpha]) in sera from 58 patients
      with systemic autoimmune diseases and 33 healthy controls. The absolute number of
      T cells and NK cells in the peripheral blood was measured in parallel using flow
      cytometry. The ability of selected cytokines to induce NK cell death was then
      measured using 3,3'-dihexyloxacarbocyanine iodide dye, propidium iodide staining,
      and caspase 3 activity. RESULTS: Levels of IL-18, IL-15, IFNgamma, and TNFalpha
      were elevated in sera from patients with systemic autoimmune diseases compared
      with normal controls. The percentage of NK cells and natural killer T cells were
      significantly decreased in the peripheral blood of patients with systemic
      autoimmune diseases compared with normal controls. Serum concentrations of IL-18,
      IL-15, and TNFalpha were inversely related to the number of NK cells in both
      patients and healthy controls. The combination of IL-18 and IL-15 or IL-18 and IL
      12 induced NK cell death in vitro. The combination of IL-18 and IL-15 or IL-18
      and IL-12 enhanced IFNgamma and TNFalpha production by NK cells in vitro.
      Cytokine-induced NK cell death is caspase-dependent and is partially blocked by
      neutralizing antibodies against TNFalpha. CONCLUSION: High levels of IL-18 and IL
      15 are associated with the decreased number of NK cells that is observed in
      patients with systemic autoimmune diseases.

PMID- 11315929
TI  - Association of fibrillin 1 single-nucleotide polymorphism haplotypes with
      systemic sclerosis in Choctaw and Japanese populations.
AB  - OBJECTIVE: Previously, we demonstrated with the use of microsatellite markers
      that a 2-cM haplotype on chromosome 15q containing the fibrillin 1 gene (FBN1)
      was strongly associated with systemic sclerosis (SSc) in the Choctaw, a
      population with high SSc prevalence. In this study, all 69 known FBN1 exons were
      sequenced to ascertain the presence of changes that might show associations with
      SSc in the Choctaw and Japanese SSc patients and controls. METHODS: Screening of
      FBN1 exons was accomplished by polymerase chain reaction-based fluorescence
      sequencing of genomic DNA using single-nucleotide polymorphism (SNP) haplotypes,
      and their frequencies were determined with a new algorithm that recognizes past
      recombination events between sites. Haplotype phylogenies were inferred using the
      median-joining network analysis. RESULTS: Five SNPs were identified in FBN1. They
      are located in the 5'-untranslated region (SNP-1), exon 15 (SNP-2), intron 17
      (SNP-3), exon 27 (SNP-4), and intron 27 (SNP-5). Only SNP-1 (T-->C) demonstrated
      an association with SSc in the Choctaw. Eleven FBN1 SNP haplotypes were
      ascertained in the Choctaw population, 2 of which (SNPs 5 and 6) were found only
      in the SSc patients. These same FBN1 SNP haplotypes were associated with SSc in
      the Japanese. CONCLUSION: A SNP in the 5'-untranslated region of FBN1 (SNP-1, C
      allele) was strongly associated with SSc in the Choctaw. Furthermore, this
      polymorphism is present on 2 unique FBN1 haplotypes found only in Choctaw SSc
      patients. The same 2 haplotypes demonstrate associations with SSc in the
      Japanese. These data extend the earlier microsatellite studies and are consistent
      with the hypothesis that FBN1 or a nearby gene on chromosome 15q is involved in
      SSc susceptibility in the Choctaw and the Japanese.

PMID- 11315930
TI  - Pulmonary capillary endothelial dysfunction in early systemic sclerosis.
AB  - OBJECTIVE: Pulmonary capillary endothelium-bound angiotensin-converting enzyme
      (PCEB-ACE) activity is a sensitive and quantifiable index of endothelial function
      in vivo. Systemic sclerosis (SSc) is characterized by endothelial damage and
      excess collagen formation, causing mainly pulmonary hypertension (PH) in the
      limited cutaneous SSc (lcSSc) subset and interstitial lung disease with pulmonary
      interstitial fibrosis (PIF) in the diffuse cutaneous SSc (dcSSc) subset. This
      study was undertaken to investigate the hypothesis that PCEB-ACE activity is
      reduced early in SSc, in the absence of PH or PIF. METHODS: Applying indicator
      dilution techniques, we measured single-pass transpulmonary hydrolysis and
      percent metabolism (%M) of a synthetic ACE substrate and calculated functional
      capillary surface area (FCSA) in 25 SSc patients and 11 controls. Substrate
      hydrolysis and %M reflect ACE activity per capillary; FCSA reflects ACE activity
      per vascular bed. RESULTS: PCEB-ACE activity was decreased in both SSc subsets.
      Among patients without PH, substrate hydrolysis and %M were decreased in patients
      with lcSSc and more profoundly in those with dcSSc; loss of FCSA normalized to
      body surface area (FCSA/BSA) was observed in dcSSc, but not in lcSSc. High
      resolution computed tomography of the lung, performed in all SSc patients,
      revealed no correlation between substrate %M, hydrolysis, or FCSA/BSA and the
      degree of PIF; 5 dcSSc and 5 lcSSc patients with no detectable PIF exhibited
      decreases in hydrolysis and %M, while FCSA/BSA was decreased only in dcSSc.
      CONCLUSION: Depression of PCEB-ACE activity, indicating pulmonary endothelial
      dysfunction, occurs early in SSc, in the absence of PH or PIF, and is more
      pronounced, at this early pulmonary disease stage, in dcSSc than in lcSSc.

PMID- 11315931
TI  - IgG from myeloperoxidase-antineutrophil cytoplasmic antibody-positive patients
      stimulates greater activation of primed neutrophils than IgG from proteinase 3
      antineutrophil cytosplasmic antibody-positive patients.
AB  - OBJECTIVE: Wegener's granulomatosis (WG) and microscopic polyangiitis (MPA) have
      been reported to be pathologically and clinically different. The aim of this
      study was to assess whether these differences could be explained by differing
      abilities of proteinase 3-antineutrophil cytoplasmic antibody (PR3-ANCA)-positive
      IgG preparations or myeloperoxidase-ANCA (MPO-ANCA)-positive IgG preparations to
      activate neutrophils (polymorphonuclear cells [PMN]) in vitro. METHODS: Using
      Percoll density gradients, PMN were isolated (concentration 2 x 10(6)/ml) and
      primed with cytochalasin B (1 ng/ml) and tumor necrosis factor alpha (TNFalpha; 2
      ng/ml). The PMN were activated with 200 microg/ml of normal IgG or ANCA.
      Activation was determined by 1) superoxide anion generation as determined by the
      superoxide dismutase-inhibitable reduction of ferricytochrome c, 2) monitoring
      fluxes in Ca2+ concentration using Fura 2-AM-loaded PMN, and 3) degranulation
      using an MPO assay. Surface expression of PR3 and MPO was determined by
      fluorescence-activated cell sorter analysis. ANCA isotypes were investigated by
      enzyme-linked immunosorbent assay. RESULTS: Activation of PMN by MPO-ANCA
      positive IgG preparations compared with PR3-ANCA-positive IgG preparations
      resulted in greater generation of superoxide anions (MPO-ANCA-positive IgG
      preparations 9.13 +/- 0.39 nmoles [mean +/- SEM], PR3-ANCA-positive IgG
      preparations 6.32 +/- 0.35 nmoles; P < 0.001), Ca2+ fluxes (MPO-ANCA-positive IgG
      preparations 0.735 +/- 0.10, PR3-ANCA-positive IgG preparations 0.33 +/- 0.098; P
      < 0.01), and MPO degranulation (MPO-ANCA-positive IgG preparations 251.98 +/-
      26.7 ng, PR3-ANCA-positive IgG preparations 145.19 +/- 19.4 ng; P < 0.001). The
      increased activation seen with MPO-ANCA-positive IgG preparations was not due to
      increased expression of MPO on the cell surface, because following TNFalpha
      priming PR3 was expressed on significantly more cells than was MPO (PR3
      expression 54.2 +/- 5.18%, MPO 31.6 +/- 3.55%; P < 0.001). IgG1 and IgG4 were the
      predominant isotypes in both MPO-ANCA-positive IgG preparations and PR3-ANCA. MPO
      ANCA contained significantly more IgG1 than did PR3-ANCA, and PR3-ANCA-positive
      IgG preparations contained significantly more IgG3. CONCLUSION: In vitro MPO-ANCA
      positive IgG preparations are more activating than PR3-ANCA-positive IgG
      preparations. The increased activation cannot be explained by increased MPO
      expression on the cell surface or greater IgG3 present in MPO-ANCA-positive IgG
      preparations. Differences in activation of PMN by these antibodies may determine
      some differences between WG and MPA.

PMID- 11315932
TI  - Expression of host defense scavenger receptors in spondylarthropathy.
AB  - OBJECTIVE: Reactive arthritis (ReA) is postulated to be caused by a defective
      host defense against gram-negative bacteria. HLA-B27 could play a role in this
      process, but does not account for the many HLA-B27 negative patients. The
      objective of this study was to test the expression of 3 macrophage scavenger
      receptors (SRs) that are responsible for innate immunity against gram-negative
      bacteria: SR class A type I (SR-AI), SR-AII, and the macrophage receptor with
      collagenous structure (MARCO). We postulate that defects in such receptors might
      also contribute to the host risk factors that increase the predisposition to ReA
      and perhaps other subtypes of spondylarthropathy (SpA). METHODS: Peripheral
      blood, synovial fluid, and synovial tissue samples were obtained from patients
      with recent Salmonella infection, ReA, other SpA, and rheumatoid arthritis (RA).
      The expression of SRs receptors was assessed by semiquantitative reverse
      transcriptase-polymerase chain reaction. RESULTS: Evaluation of the peripheral
      blood mononuclear cells (PBMC) from 4 patients who were recently infected with
      Salmonella, showed that PBMC from 2 patients who developed ReA expressed positive
      levels of MARCO, while PBMC from 2 patients who recovered from infection without
      sequelae did not. The synovial fluid mononuclear cells (SFMC) from some ReA
      patients expressed MARCO, but the levels were only moderate. The level of MARCO
      in the SFMC from the SpA patient group was low. In marked contrast, MARCO
      expression was high in almost all samples of RA SFMC. These findings also
      extended to synovial tissues. CONCLUSION: Expression of the host defense gene
      MARCO was susceptible to modulation, not only during infections, but also in the
      inflammatory arthritis conditions RA and SpA. MARCO is a variable to be
      considered as a candidate factor that might contribute to ReA.

PMID- 11315933
TI  - Features of somatization predict the onset of chronic widespread pain: results of
      a large population-based study.
AB  - OBJECTIVE: Chronic widespread pain, the clinical hallmark of the fibromyalgia
      syndrome, is associated with other physical and psychological symptoms both in
      patients studied in a clinical setting and in those identified in the community.
      The present study was undertaken to examine the hypothesis that psychological and
      physical indicators of the process of somatization predict the development of new
      chronic widespread pain. METHODS: In this population-based prospective study,
      1,658 adults ages 18-65 years completed a detailed pain questionnaire, which
      included a pain drawing. They also completed the following psychosocial
      instruments: General Health Questionnaire, Somatic Symptom Checklist, Fatigue
      Questionnaire, and Illness Attitude Scales. Individuals were followed up at 12
      months, at which time 1,480 (93% of subjects still living at their baseline
      address) provided data on pain status, using the same instruments. RESULTS: At
      baseline, 825 subjects were classified as pain free and 833 as having pain not
      satisfying criteria for chronic widespread pain. Of those, 18 (2%) and 63 (8%),
      respectively, were classified as having chronic widespread pain at followup.
      After adjustment for age and sex, there were strong relationships between
      baseline test scores and subsequent risk of chronic widespread pain (odds ratio
      for the Somatic Symptom Checklist 3.3; odds ratio for the Illness Behavior
      subscale of the Illness Attitude Scales 9.0). All 95% confidence intervals
      excluded unity. These associations were independent of baseline pain status.
      CONCLUSION: Subjects who are free of chronic widespread pain are at increased
      future risk of its development if they display other aspects of the process of
      somatization. Data from this population-based prospective study lend powerful
      support to the hypothesis that chronic widespread pain can be one manifestation
      of the somatization of distress.

PMID- 11315934
TI  - Expression of Sox9 and type IIA procollagen during attempted repair of articular
      cartilage damage in a transgenic mouse model of osteoarthritis.
AB  - OBJECTIVE: To determine the capacity of chondrocytes in aging and degenerating
      articular cartilage to produce major components of the extracellular matrix and
      maintain the normal structure of articular cartilage in a transgenic mouse model
      of osteoarthritis. METHODS: Transcription factor Sox9 was used as an indicator of
      the activation and maintenance of the articular chondrocyte phenotype. Knee
      joints of Del1 mice carrying 6 copies of the pro alpha1(II) collagen transgene
      with a short deletion mutation were analyzed at the age of 10 days and at 2, 3,
      4, 6, 9, and 15 months by Northern hybridization, RNase protection assay,
      quantitative reverse transcription-polymerase chain reaction, and
      immunohistochemistry. Nontransgenic littermates were used as controls. RESULTS:
      We demonstrated the presence of Sox9 in articular chondrocytes during
      development, growth, and aging, with the highest messenger RNA levels during the
      period of rapid growth. With the appearance of degenerative lesions in articular
      cartilage, 2 repair processes were observed. Local proliferation and activation
      of chondrocytes rich in Sox9, surrounded by type IIA procollagen and
      proteoglycans, was seen in articular cartilage. In contrast, metabolically
      inactive chondrocytes were observed at the margins of the defects. They were
      devoid of Sox9 and were surrounded by a proteoglycan-poor matrix. Sometimes, the
      lesions were filled with repair tissue that contained type III collagen but
      little proteoglycan or type II collagen. CONCLUSION: The results indicate that
      chondrocytes in mature articular cartilage are capable of inducing the production
      of Sox9 and type IIA procollagen, which is typical of early chondrogenesis.
      Degenerative defects in the knee joints of transgenic Del1 mice are associated
      with local activation of chondrocytes, which probably contributes to the repair
      process. In other areas, the repair process produces a noncartilaginous matrix,
      which is insufficient to maintain the integrity of articular cartilage and which
      allows degeneration to proceed.

PMID- 11315935
TI  - Development and characteristics of a synovial-like interface membrane around
      cemented tibial hemiarthroplasties in a novel rat model of aseptic prosthesis
      loosening.
AB  - OBJECTIVE: Aseptic prosthesis loosening (APL) is related to the formation and
      aggressive growth of a synovial-like interface membrane (SLIM) between prosthesis
      and bone. However, investigation of the early phases of SLIM development in
      humans presents major difficulties. This study was undertaken to develop and
      characterize the usefulness of a novel animal model of APL that is based on an
      established model of defined exercise in a running wheel by Wistar rats that have
      been subjected to intracranial self-stimulation (ICSS). METHODS: Cemented tibial
      hemiarthroplasties were implanted into the left knees of 7 male Wistar rats.
      After 2 weeks, exercise in a running wheel was started in all rats, with a
      running-load of 2 hours/day for 5 days/week. Six months postoperatively, the knee
      joints were removed, decalcified, and embedded in paraffin. Histologic evaluation
      on hematoxylin and eosin-stained sections was performed to investigate the
      development of a SLIM and the presence of cement debris particles. To
      characterize the SLIM on a molecular level and investigate growth-regulating
      factors, the expression of transforming growth factor beta (TGFbeta) and the anti
      apoptotic molecule Bcl-2 was analyzed by immunohistochemistry. RESULTS: Although
      the prostheses appeared mechanically stable after 6 months, the development of
      SLIM with areas of bone resorption was seen in all samples. Resembling human
      SLIM, these membranes consisted of loose fibrous tissue, with cement debris
      particles located particularly at sites originally attached to the prostheses.
      Immunohistochemistry studies revealed the expression of TGFbeta and Bcl-2 in all
      specimens. Interestingly, staining for TGFbeta and Bcl-2 was restricted to areas
      where the SLIM were attached to bone. In contrast, there was only negligible
      expression of both proteins at sites adjacent to the prostheses. CONCLUSION: Our
      findings demonstrate that the ICSS Wistar rat model constitutes a feasible tool
      for studying early stages of APL, and specifically the effect of defined running
      exercise on SLIM formation. The results further suggest that both cellular
      proliferation, as stimulated by TGFbeta, and altered apoptosis contribute to
      early stages of SLIM formation. The expression patterns of TGFbeta and Bcl-2
      indicate that the growth of the SLIM is initiated and promoted from the bone
      rather than from the prosthesis.

PMID- 11315936
TI  - Treatment of chronic sialadenitis in a murine model of Sjogren's syndrome by
      local fasL gene transfer.
AB  - OBJECTIVE: Infection of Fas (Fas/CD95)-mutant C57BL/6 (B6)-lpr/lpr mice with
      murine cytomegalovirus (MCMV) leads to a chronic sialadenitis similar to that of
      Sjogren's syndrome (SS). The aim of this study was to evaluate whether chronic
      sialadenitis would also occur in Fas ligand (FasL/CD95L)-mutant B6-gld/gld mice
      upon infection with MCMV and whether the expression of FasL by local gene
      transfer using recombinant adenoviral vectors would be an effective therapeutic
      strategy. METHODS: B6-gld/gld mice were infected intraperitoneally with MCMV, and
      salivary glands were analyzed histologically at different time points. For
      treatment of sialadenitis, recombinant adenoviral vectors expressing the fasL
      gene (AdLoxpFasL + AxCANCre) or the lacZ gene (AdCMVLacZ) were locally injected
      into the salivary glands of MCMV-infected B6-gld/gld mice and uninfected B6-+/+
      and B6-gld/gld mice. RESULTS: Following MCMV infection, B6-gld/gld mice developed
      an acute and chronic sialadenitis characterized by multiple foci of infiltrating
      T cells. After local injection of adenoviral vectors, high levels of lacZ or fasL
      gene expression could be detected in acinar and ductal cells. Treatment of acute
      and chronic sialadenitis in B6-gld/gld mice with local fasL gene transfer
      resulted in a significant reduction in the number of inflammatory foci and tissue
      destruction in salivary glands compared with mice treated with AdCMVLacZ. Despite
      high levels of FasL expression after injection of recombinant vectors, <5% of
      ductal and acinar cells were TUNEL positive, demonstrating that, in this model of
      SS, acinar and ductal cells were not highly sensitive to FasL-mediated apoptosis.
      CONCLUSION: Chronic sialadenitis similar to that of SS developed in B6-gld/gld
      mice after MCMV infection. FasL expression was reconstituted by local gene
      transfer, resulting in significant reduction of infiltrating mononuclear cells,
      which indicates that local gene transfer of fasL might be a novel treatment for
      chronic sialadenitis.

PMID- 11315937
TI  - Hereditary angioedema with a de novo mutation of exon 8 in the C1 inhibitor gene
      showing recurrent edema of the hands around the peripheral joints: importance for
      the differential diagnosis of joint swelling.
AB  - We describe a patient with hereditary angioedema (HAE), showing recurrent edema
      around the peripheral joints. Her symptoms began at the age of 18 with hand
      swelling distal to the wrist joints. Until she was referred to our hospital 3
      years after her initial symptoms, she was still undiagnosed, although she was
      suspected of having rheumatoid arthritis. Laboratory examination showed reduced
      levels of CH50 and C4 with normal C3 levels. The C1 inhibitor (C1-INH) was
      decreased to 5 mg/ml, with remarkably reduced activity. Although these findings
      were compatible with a diagnosis of HAE, there were no episodes of skin edema in
      her family. To establish the diagnosis, we carried out DNA analysis of the C1-INH
      gene, which revealed a newly identified de novo mutation of G to A at nucleotide
      16869 in exon 8. As described in this patient, localized edema around the
      peripheral joints may be the only manifestation of HAE. HAE should therefore be
      taken into consideration for the differential diagnosis of joint swelling.

PMID- 11315938
TI  - Bilateral symmetric inflammatory reaction to hylan G-F 20 injection.

PMID- 11315939
TI  - Ferritin and serum transferrin receptor predict iron deficiency in anemic
      patients with rheumatoid arthritis.

PMID- 11315940
TI  - Systemic lupus erythematosus in three ethnic groups. VIII. Lack of association of
      glutathione S-transferase null alleles with disease manifestations.

PMID- 11315942
TI  - Morphological dynamics of cumulus-oocyte complex during oocyte maturation.
AB  - The recent advances on the cytoplasmic regulators of the induction of germinal
      vesicle break down, maturation and degeneration of oocytes, and glycosaminoglycan
      composition during cumulus expansion of cumulus-oocyte complexes are discussed.
      A) Inactive mitogen-activated protein kinases (MAPKs) are present in the oocytes
      at germinal vesicle (GV) stage, and are activated with germinal vesicle breakdown
      (GVBD), and remain highly active throughout maturation in porcine oocytes.
      Inactive MAPKs are localized in the cytoplasm of GV-arrested oocytes and active
      MAPKs were detected in the GV just before GVBD. B) Cumulus expansion of porcine
      cumulus-oocyte complexes (COCs) was reduced by oocy tectomy. The profile of total
      glycosaminoglycan synthesis was attributed to hyaluronic acid rather than
      chondroitin sulfate in intact COCs and oocytectomy reduced hyaluronic acid
      synthesis. C) The abnormalities of chromosomes and alpha-tubulin morphology were
      observed in the oocytes of c-mos deficient mice. MAPK activity of c-mos deficient
      oocytes did not significantly fluctuate throughout maturation and was clearly
      lower than that of wild-type oocytes. One of the most drastic abnormalities in c
      mos knockout mouse oocytes was their entrance into the interphase instead of
      second meiosis after first polar body emission. D) Reverse
      transcriptase/polymerase chain reaction-Southern blot hybridization demonstrated
      positive expression of Fas in intraovarian mouse oocytes. In contrast, expression
      of Fas ligand was detected in granulosa cells. These findings were histologically
      confirmed by in situ hybridization with Fas- and FasL-specific probes. Co-culture
      of intact and zona-free eggs and granulosa cells demonstrated positive TUNEL
      staining only zona-free eggs.

PMID- 11315941
TI  - Cyclooxygenase 2 inhibition and thrombosis: comment on the article by Crofford et
      al.

PMID- 11315943
TI  - Bovine cumulus-corona cells in maturing oocytes. A scanning electron microscopic
      study.
AB  - The ultrastructural features of cumulus-corona cells surrounding maturing oocytes
      in bovine were studied by means of scanning electron microscope in order to
      provide a detailed description of their surface changes during oocyte maturation.
      Cumulus corona cell complexes of immature oocytes showed a compact aspect with
      narrow intercellular spaces. The spaces around mature oocytes enlarged because
      they were progressively filled with abundant microfibrillar extracellular matrix.
      In cumulus corona cells complexes of immature oocytes very numerous long and
      filiform microvilli were observed, whereas the cumulus corona cell surface
      surrounding mature oocytes showed occasional large cytoplasmic protrusions along
      with scanty microvilli and numerous blebs.

PMID- 11315944
TI  - Confocal laser fluorescence scanning microscopy of the oolemma distribution of
      monoclonal antibodies against mouse and human egg surface membrane.
AB  - Monoclonal antibodies were raised against zona-free mouse oocytes by intrasplenic
      immunizations. Antibodies, which detected antigen epitopes in unfertilized but
      not in fertilized mouse eggs (fertilization-specific antibodies) and which in
      addition recognized epitopes in unfertilized human oocytes (mouse-human cross
      reacting antibodies) were used to visualize the distribution of their
      corresponding antigens by confocal laser fluoresence scanning microscopy (CLFSM).
      We found that among 26 antibodies tested, two ones showed a patch pattern. Since
      a patchy distribution of cell membrane molecules indicates the presence of
      integral proteins with ability to transduce signals to the cytoplasm, we suggest
      that the method here applied will select for those oolemma molecules that could
      be involved in the fusion of sperm cells.

PMID- 11315945
TI  - Paracrine interaction in testicular somatic cells.
AB  - Initiation of spermatogenesis is regulated by signals derived from intratubular
      Sertoli cells as well as extratubular Leydig cells, both being systemic targets
      of hypophyseal gonadotropins. In addition to Leydig and Sertoli cells, a number
      of other cell types are present in the testis viz. peritubular cells, macrophages
      and vascular components. The specific paracrine functions of these cells are only
      partially understood. The peritubular and Sertoli cells form the structural
      scaffold of the germinal epithelium and are responsible for intratubular
      pressure, release and transport of spermatozoa and the formation of the blood
      testis barrier. We have performed ex vivo and in vitro studies on the
      ultrastructure of peritubular and Sertoli cells and the distribution of steroid
      hormone receptors, cytoskeletal and extracellular matrix proteins using rat
      testes from different stages of postnatal development. Morphological observations
      were related to in vitro findings of gene expression on the respective hormones
      and structural proteins. In the developing rat testis, the peritubular cells
      showed a strong and consistent expression of fibronectin, entactin, laminin as
      well as the glucocorticoid, androgen, estrogen and partially also the
      progesterone receptor, while the Sertoli cells were devoid of glucocorticoid
      receptor and entactin. The glucocorticoid receptor was present in around 20% of
      the intratubular germ cells (in the 2nd postnatal week) and in 50% of the
      peritubular cells. In Leydig cells also, the expression reached its climax in the
      3rd weak and declined thereafter. This is perhaps pointing to a differentiation
      inhibiting role of glucocorticoids in gonocyte differentiation. In the 3rd
      developmental week, the androgen receptor was present in about 15% of all
      gonocytes and later in 50% of peritubular cells and about 40% of interstitial
      cells. The estrogen receptor was absent in peritubular cells of the adult testis.
      The progesterone receptor was present in about 30% of the peritubular and 25% of
      the Leydig cells. Taking into account the significant increase in seminiferous
      tubules following postnatal developmental day 18, the peritubular cells seem to
      exert an androgen dependent growth stimulus to the seminiferous cords perhaps via
      the Sertoli cells. In vitro studies of peritubular and Sertoli cells cultured
      either alone or in co-culture showed by RT-PCR the expression of the androgen and
      the glucocorticoid receptors in both cell types, as well as fibronectin.
      Secretion of fibronectin occurred in a clear-cut time-dependent increase in
      monocultures of peritubular cells (on day 3 of culture). In co-cultures of
      Sertoli and peritubular cells, fibronectin bio- synthesis was down-regulated. The
      paracrine interplay between extracellular matrix and hormonal signals joining
      peritubular and Sertoli cells is essential in the differentiation of the
      seminiferous tubules.

PMID- 11315946
TI  - The ultrastructural localization of NADPH-diaphorase enzymatic activity in the
      Leydig cells of mouse. effects of ethanol administration.
AB  - The effects of the chronic ethanol treatment on the NOS-related NADPH-diaphorase
      activity were described in the mouse Leydig cells by means of transmission
      electron microscope. The recovery of the Leydig cells was also examined during a
      period of four weeks. About 10% of the Leydig cells showed various degrees of
      morphological alterations, consisting in increased number of lipid droplets,
      rarefaction and vacuolization of the cytoplasmic matrix. Other groups of Leydig
      cells (about 10%) revealed evident signs of degeneration. The NADPH-d activity
      was reduced both in apparently normal and injured Leydig cells and a moderate
      enzymatic reaction was only detected in the smooth endoplasmic reticulum. A week
      after the treatment an increased number of the degenerating Leydig cells and a
      further reduction of the enzymatic reaction were observed. Then, the Leydig cells
      showed a progressive recovery and four weeks after the treatment they exhibited a
      normal morphology and NADPH-d enzymatic reaction. These results demonstrated for
      the first time the inhibition of NOS activity in the Leydig cells after chronic
      ethanol administration.

PMID- 11315947
TI  - Subsurface crypts and interstitial cells in the ovary of the seal (Phoca vitulina
      vitulina): light and electron microscopic findings.
AB  - This morphological study on the ovary of the seal focuses on two structures of
      special interest: the subsurface crypts and the interstitial cells. Ovaries from
      110 seals (from 1,5 months to 12 years) were used. Most of the seals of our study
      originated from German North Coast, a few from Island. The ovaries were examined
      by light microscopic as well as by transmission and scanning electron microscopic
      techniques. The seal's ovary conforms to the basic structure of the ovary of
      other mammalian species. However, the surface epithelium cell layer lowers itself
      into an epithelium lined - broadly branching system of subsurface crypts. The
      size and extent of these crypts and the proliferation of the epithelium appear to
      be mainly related to the reproductive activity. The ultrastructure of crypt
      epithelium cells indicates a remarkable metabolic activity. In juvenile ovaries
      cell buds proliferate from the crypt epithelium and grow as plug-like strands
      into the cortical stroma. These cells show ultrastructural changes during their
      proliferation and appear to transform into steroid producing interstitial cells.
      In the adult seal the interstitial cells are completely differentiated
      established and, according to their origin, can be divided into epithelial and
      fibroblastic interstitial cells. It is suggested that a major function of the
      crypts is the formation of the ovarian blastema with particular reference to
      ovarian interstitial cells. The intensive proliferation of interstitial cells is
      in agreement with the extraordinary high level of 350 pmol estrogen/l blood
      serum.

PMID- 11315948
TI  - Ultrastructural dynamics of human testicular cords from 6 to 16 weeks of
      embryonic development. Study by transmission and high resolution scanning
      electron microscopy.
AB  - When the embryo is 6-week-old the gonad is composed mostly of migrating
      primordial germ cells, surface coelomic mesothelium and mesenchymal cells. At 7
      weeks of gestation (wg) testicular cords consist of prespermatogonia, larger,
      with a more regular outline and higher mitotic activity than primordial germ
      cells, embraced by somatic pre-Sertoli cells. The morphofunctional development of
      Sertoli cells defines testicular differentiation. Towards 7.5 wg the gonad is
      finally in its differentiated stage; the basal lamina of the cords becomes
      distinguishable, testicular cords radially branch and elongate, and Leydig cells
      are clearly recognized. Primordial germ cells are large and spherical, with
      rounded and eosinophilic nuclei and large nucleoli. Pre-Sertoli cells, in turn,
      show round or columnar nuclei and rough endopasmic reticulum. Prespermatogonia
      and mostly pre-Sertoli cells actively proliferate. Many interdigitations and
      cytoplasmic processes are observed between neighboring pre-Sertoli cells and
      between pre-Sertoli cells and prespermatogonia. A sort of com partmentalization
      is established inside the cords in which pre-Sertoli cells tend to localize
      closer to the basal membrane embracing the prespermatogonia with long and thin
      cytoplasmic processes. Between 14 and 16 wg the most significant changes besides
      maximum development of Leydig cells are differentiation of mesenchymal cells
      around the cords into future peritubular cells and maturational changes of pre
      Sertoli cells. These likely reveal a peak coinciding in time with reported
      increases in either testosterone production and Mullerian Inhibiting Substance
      secretion. During the period herein considered testicular cords show no lumen
      neither any sign of canalization so they cannot be termed "tubules".

PMID- 11315949
TI  - Macrophages are present not only in atretic mature follicles but also in the
      growing follicles of the guinea pig ovary.
AB  - In atretic ovarian follicles, massive groups of apoptotically dead granulosa
      cells are eliminated by two kinds of phagocytic cells: intact granulosa cells and
      macrophages. Using mature guinea pig ovaries, this study further examined whether
      or not phagocytic cells are present in the growing follicles by means of light
      and electron microscopy. Within healthily growing follicles, small numbers of
      large round cells were found among the granulosa cells. By electron microscopy,
      the nucleus of the large cells appeared to be pushed aside by prominently
      expanded large cytoplasmic vacuoles together with abundant large and small
      lysosomes. These cells were identified as macrophages. This is the first report
      to demonstrate macrophages within the growing follicles of the guinea pig. The
      importance of the intrafollicular macrophages is suggested in connection with the
      dynamics of the follicle, such as its development and atresia.

PMID- 11315950
TI  - The microvasculature of the corpus luteum in pregnant rabbit. A scanning electron
      microscopy study of corrosion casts.
AB  - The vascular network of pregnant rabbit ovaries was studied by means of scanning
      electron microscopy (SEM) of corrosion casts, in order to evaluate the
      morphofunctional changes of the microcirculation of corpus luteum (CL). Pregnant
      rabbit ovary showed an overwhelming vascularization. Ovarian hilus displayed an
      increase in the arterial spirallisation. The arterial spiral pattern was present
      along the entire vessel course, up to CL tissues. The CL of pregnancy was
      supplied by wide vascular plexuses (2-5 plexuses were found in each pregnant
      ovary) whose major axis was about 2 mm. Luteal capillaries showed a tortuous
      course and were arranged in a three-dimensional, wide and rounded-meshed network.
      Postcapillary venoconstrictions were present. The venous drainage appeared more
      developed then the arterial supply. Tight artero-venous contacts in hilar,
      juxtamedullar and medullar regions of the ovary were observed. These results
      clearly show that the morphofunctional expression of CL of pregnancy is greatly
      dependent on its hemodynamic control. In particular, the increase of
      spirallisation exhibited by the arteries during pregnancy is likely to be
      considered a significant functional change. The spirallisation likely is a device
      for reducing the blood pressure through the CL. The artero-venous contacts, also
      previously described in hCG stimulated (pseudopregnant) ovaries, may support a
      counter-current like system that may allow a veno-arterial exchange of small
      molecules through the wall of the facing vessels. In addition, in 10-day pregnant
      rabbit CL the consolidation of a well-developed capillary network was revealed,
      which is a sign that the CL of pregnancy reached the full morphofunctional
      maturation. Furthermore, the CL of 10-day pregnant rabbit did not present
      significant capillary permeabilization and dilation or angiogenic processes,
      aspects that were previously found in stimulated periovulatory ovaries. Indeed,
      changes of the arterial supply and venous drainage of the CL of pregnancy were
      demonstrated. This suggests that the control of the blood flow through the CL of
      pregnancy may be transferred from the local capillary microcirculation to the
      regional artero/venous circulation. This may be probably related to the
      significant increase of the ovarian blood flow necessary for the maintenance of
      CL endocrine functions during pregnancy.

PMID- 11315951
TI  - Cellular proliferation in bovine luteal tissues of different reproductive states
      as demonstrated by Ki-67 immunocytochemistry.
AB  - Luteal tissue specimens of corpora lutea of oestrous cycle and pregnancy, post
      partum corpora lutea, and of luteinised follicular cysts of cows were harvested
      at slaughter. Cellular proliferation was examined employing Ki-67
      immunocytochemistry. Ki-67 immunoreactivities could mainly be demonstrated within
      the nuclei of the theca interna and theca externa derived cell populations of
      cyclic corpora lutea. These cells obviously differentiated into vascular cells,
      connective tissue cells and small luteal cells. Proliferative activity was
      strongest in young corpora lutea and markedly reduced in the mature ones. During
      involution of corpora lutea of oestrous cycle Ki-67-positive cells were mainly
      found in vascular walls and connective tissue districts. Luteinised follicular
      cysts closely resembled cyclic corpora lutea. Corpora lutea of pregnancy
      exhibited foci of immunopositive cells close to blood vessels and connective
      tissue septae during whole gestation. Post partal luteal involution was
      characterised by Ki-67-positive cells within vascular walls and the surrounding
      stroma. Results suggest that luteal cellular proliferation is restricted mainly
      to theca interna-derived cells, which may differentiate to stromal cells and
      parenchymal cells.

PMID- 11315952
TI  - Regulation of ovarian hyperluteinization.
AB  - Adult female rats with neonatally damaged posterior hypothalamus, made by a
      transversal cut, were investigated. Plasma levels of prolactin (PRL),
      gonadotropic hormones (GTH) and female gonadal steroids (GS) were determined by
      radioimmunoassay. The animals were sacrificed, at the ages of 4 and 6 months and
      their hypothalamus, pituitary gland, ovary and uterus were examined using light
      microscopy. The results can be summarized as follows: body mass of animals, with
      damaged posterior hypothalamus, was significantly reduced. Masses of luteinized
      ovaries were increased and uterine tissues decreased. Serum levels of PRL were
      significantly increased and luteinizing hormone (LH) decreased. Ultrastructural
      changes in the corpora lutea (CL), previously described, showed clear signs of
      their reduced capacities to produce GS, both estradiol (Oe) and progesterone (Pg)
      per total ovarian mass. However, prostaglandin 2 alfa (PGF2alpha) known as a
      luteolytic factor, was also diminished in the evidently retarded endometrium. As
      a result of decreased plasma values of LH, Pg and PGF2 alpha, luteolysis of CL in
      hyperluteinized ovaries did not occur, and their new generations were accumulated
      during subsequent cycles. The character of interruption and recovery of aminergic
      and peptidergic neurons, involved in regulation of hypothalamic-pituitary gonadal
      axis and feed-back effects of steroid hormones, require further studies.

PMID- 11315953
TI  - Immunoglobulins in the human male genitourinary tract.
AB  - Human male genitourinary tract was processed for the immunohistochemical
      demonstration of IgG and IgM, in order to verify the presence and the source of
      these immunoglobulins. Only the epithelia of the prostate gland and urethra
      showed a marked IgM-immunopositivity, localized in the cytoplasm of apical cells.
      An intense immunoreactivity for IgG was observed in the apical cells of the
      vesical epithelium; a less intense immunoreactivity for IgG in the pelvic apical
      epithelial cells was found. Immunostaining in the ureteric epithelium was absent.
      Clusters of IgM- and IgG-positive immunocompetent cells were present in the
      subepithelial layers of the organs observed in our study. This study indicates
      that IgM, present in mucosal surfaces, derived from an active secretion, as well
      as secretory IgA, whereas most of the IgG present in the human seminal plasma
      were probably due to transudation process. Immunoreactivity for IgG in the
      vesical and pelvic epithelia could depend upon to virus-specific IgG antibodies
      produced by the mucosa. This in turn can contribute to the total antiviral
      activity in mucosal secretions.

PMID- 11315954
TI  - The prostate gland and prostate carcinogenesis.
AB  - Despite extensive research, the mechanisms of prostate carcinogenesis are not
      well understood. The slow progress in this area is due, at least in part, to lack
      of a suitable animal model for prostate carcinogenesis. We have developed an
      animal model, based on the existing sex hormone-induced prostate carcinogenesis
      in the Noble rat, by substantially increasing the dosage of testosterone while
      keeping the level of estrogen unchanged. Using the modified method of combination
      of testosterone and estradiol-17beta (T+E2), it has been shown in Noble rats that
      prostate carcinogenesis followed a multi-step process involving hyperplasia,
      dysplasia, and carcinoma. We have demonstrated the importance of TGF-alpha, TGF
      beta1 and bFGF in the development of prostate carcinogenesis. This study also
      established the roles of VEGF and IGF-1, initially as paracrine factors in
      epithelial-stromal interactions during the process of carcinogenesis and
      subsequently switching over to an autocrine mode during the establishment of
      carcinoma.

PMID- 11315955
TI  - Langerhans cells in the human oviduct mucosa.
AB  - Langerhans cells (LCs) are the predominant antigen-presenting cells in epithelial
      tissues. They have been known to be present in the vagina and uterine cervix. In
      the present study, localization of LCs in the oviduct was investigated by
      electron microscopy and immunohistochemistry using an anti-CD1a (CD; cluster of
      differentiation) antibody. Although the cell density was variable, CD1a-positive
      LCs were detected in the oviduct epithelium. Their occurrence was most common in
      women at the age of 40 to 59. LCs extended cell processes along the base of the
      epithelium and were ultrastructurally characterized by rod-shaped Birbeck
      granules and a well-developed Golgi apparatus. LCs, together with lymphocytes and
      macrophages, are considered to engage in the mucosal immune system of the
      oviduct.

PMID- 11315956
TI  - Myofibroblasts in the mucosal layer of the uterine tube.
AB  - Uterine tubes from cow, sheep, horse, pig, dog, cat, rabbit, and guinea pig were
      examined immunohistochemically for presence and distribution of contractile cells
      in the mucosal lamina propria. We tested for the presence of alpha-smooth muscle
      actin, tropomyosin, desmin, smooth muscle myosin (heavy chain) and cytoskeletal
      proteins vimentin and cytokeratin. Immunostaining for alpha-smooth muscle actin
      showed two distribution patterns: either positive cells were freely dispersed in
      the mucosal lamina propria or a distinct subepithelial layer of positive cells
      was seen. The first distribution pattern was found in the isthmic uterine tube
      segments of all animals examined. Alpha-smooth muscle actin was colocalized with
      tropomyosin (all species), desmin (horse, sheep), and smooth muscle myosin
      (sheep, cow). All these cells were found reactive with anti-vimentin but not with
      anticytokeratin and therefore were classified as myofibroblasts. A distinct
      subepithelial layer of alpha-actin and tropomyosin positive cells was seen in
      horse fimbriae. In other examined species alpha-smooth muscle actin
      immunoreactivity in the subepithelial region was very weak. Contractile cells in
      the uterine tube mucosa were supposed to influence mucosal condition and
      motility, and therefore to play a role in gamete transport.

PMID- 11315957
TI  - Variation in the estrogen receptor content of canine uterine tissue throughout
      the estrous cycle.
AB  - The estrogen receptor (ER) was visualized immunohistochemically in paraffin
      sections of the canine uterus using a monoclonal antibody. The ER-expression was
      quantified by means of an immunohistochemical score. In the uterine horns highest
      scores were found during proestrus and lowest scores during early metestrus.
      Staining scores in the uterine body and cervix were high during estrus and
      metestrus compared with the uterine horns. A negative correlation was found
      between serum progesterone levels and immunohistochemical staining for ER in the
      uterine horns. The fluctuations in immunohistochemical scores were more
      pronounced in the endometrial stroma cells than in the epithelial cells of the
      uterine horns and therefore stromal cells may be of higher importance than
      epithelial cells concerning cyclic endometrial changes and uterine pathology.

PMID- 11315958
TI  - Pregnancy-induced denervation of the human uterine artery correlates with local
      decrease of NGF and TrkA.
AB  - Pregnancy induces transient and reversible denervation of the mammalian uterus
      and uterine artery which origin remains still unclear. It is well established
      that the density of sympathetic innervation is regulated by the levels of
      peptidergic diffusible growth factors, especially nerve growth factor (NGF).
      Whether a decrease of NGF and/or its signal-transducing receptor TrkA are
      involved in this physiological denervation of the uterine artery during pregnancy
      has not been analyzed. The aim of the present study is to analyze this topic on
      human uterine artery using ELISA, Western blotting and immunohistochemistry
      (associated to quantitative image analysis). The material was obtained from
      surgical pieces (hysterectomy) of non-pregnant and pregnant women from 4 to 16
      weeks of gestation. The density of innervation for tyrosine hydroxylase assessed
      in whole mount samples of uterine artery, as well as the density of nerve fibers
      identified with other general nerve (PGP 9.5 and NFP) or Schwann cell (S-100
      protein) markers was significantly reduced (p<0.05) in the uterine artery from
      pregnant woman. On the other hand, the tissular levels of NGF, the density of
      TrkA, and the immunostaining for both NGF and TrkA, were significantly reduced in
      uterine arteries from pregnant patients. These results strongly suggest that the
      physiological denervation occurring in the uterine artery during pregnancy is
      related to a decrease in the availability of NGF by nerve fibers, and to the
      impossibility to mediate its effect due to a remarkable decrease in the signal
      transducing TrkA receptor.

PMID- 11315959
TI  - Scanning electron microscopy of the canine placenta.
AB  - The zonary placenta of the dog is peculiar in providing three morphologically and
      functionally distinct areas for transplacental exchange: the endotheliochorial
      labyrinth of the girdle zone, the hemochorial hemophagous zone of the marginal
      hematoma and the epitheliochorial free polar zone. Besides, the yolk sac persists
      throughout pregnancy. Scanning electron microscopy (SEM) was used to study these
      structures comprehensively with special emphasis on natural surfaces because of
      their relevance for exchange processes. Unequal cell diameter was typical for
      trophoblast cells. Surface specializations were observed on trophoblast cells
      lining the marginal hematoma, the free polar zone and the glandular chambers as
      well as on uterine epithelial cells of the glandular chambers and of the deep
      glands. In addition, maternal and fetal endothelial cells in the labyrinth showed
      major differences. Whereas fetal endothelial cells were extremely thin and
      polygonal in shape, maternal vessels were lined by thick endothelial cells
      exhibiting a complex interdigitation pattern of cytoplasmic processes. Thus, most
      of the natural surfaces could readily be distinguished by SEM due to their
      typical appearance.

PMID- 11315960
TI  - Morphogenesis of the human genital tract.
AB  - The origin and development of the Wolf and Muller ducts are systematically
      studied in human embryos of 5 mm vertex-coccis (VC) to 39,5 weeks' post
      fertilization human fetuses. The fusion of both Muller ducts is described, as
      well as embryonic and fetal uterus development. Basic elements, which constitute
      the genital tract, are equally formed in both sexes and it is from that common
      structure that at a specific time the sexual differentiation of the genital tract
      is transformed in one or another sex. This implies that, as it is happened with
      the gonad, genital tract passes through a common or indifferent stage in which
      morphologic differences between both sexes do not exist, and another phase of
      sexual differentiation in which several factors of multiple origin appears.

PMID- 11315961
TI  - The extracellular matrix of normal human placental villi at term: a scanning
      electron microscopy study.
AB  - The three-dimensional organisation of the extracellular fibrillar matrix in
      normal human placental villi at term is investigated by scanning electron
      microscopic after 2N-NaOH-maceration technique. The latter method consists of a
      chemical digestion of cellular components of the villi that allows the
      visualisation of the extracellular fibrillar network in a real three-dimensional
      fashion by scanning electron microscope. By this approach, the extracellular
      fibrillar matrix, mainly composed by collagen fibrils, forms a continuous
      skeleton within the whole villous system of the placenta. This sort of
      collagenous fibrillar skeleton forms the axis of chorionic villi and connects
      them with the basal plates. Significant differences in quantity and arrangement
      of the extracellular matrix are observed at the various levels of the villous
      ramification. In fact, in the stem villi, the fibrillar extracellular matrix is
      considerable and the fibres are arranged longitudinally at the villous surface
      (outer fibrils) and circularly in the inner core of the villous around the wall
      of the fetal vessels (inner fibrils). On the contrary, in mature intermediate and
      terminal vili, the extracellular fibrillar matrix is significantly reduced and
      the fibrils are mainly arranged in a thin circular layer around the capillaries
      and sinusoids. The present study confirms morphologically the existence of a
      diverse organization of the extracellular matrix specific for the various levels
      of the villous ramification as suggested by previous immunohistochemical studies.
      Moreover, the presence of a highly organized collagenous fibrillar skeleton as
      observed in our study, stress the important mechanical role of the extracellular
      matrix in sustaining the chorionic fetal vessels and the trophoblastic layer.
      Furthermore, the fine reticular-meshed network of this skeleton observed in the
      terminal villi suggests an additional role of the extracellular matrix to ensure
      a favorable milieu for active feto-maternal exchanges at this level of the
      villous tree.

PMID- 11315962
TI  - Purification and characterization of primordial germ cells in male rat fetuses.
AB  - The primordial germ cells in the testes of male rat fetuses at 15.5 days post
      coitum were purified by equilibrium centrifugation on a discontinuous Percoll
      gradient column after dissociation by trypsin-EDTA treatment and characterized
      before and after purification. Gonadal dimorphism first becomes evident at 14.5
      days post coitum but the "stripey" appearance can not be observed in every fetal
      testis. Complete dissociation of the testes was essential for successful
      purification of the primordial germ cells. Using the isolation technique
      described here, over 50% of the primordial germ cells (around 10,000) could be
      harvested from each fetal testis with about 95% viability as determined by trypan
      blue exclusion and 90% purity, as determined by alkaline phosphatase
      histochemistry. Prior to and following purification, the primordial germ cells
      were characterized by their large size and round or oval nuclei. Their nucleoli
      were large and located centrally or eccentrically in the nucleus. The
      mitochondria were large, and round or oval, and there were a great number of
      ribosomes and polysomes dispersed in the cytoplasm. All these characteristics
      were similar to that of type A spermatogonia in postnatal testes. These
      morphological aspects correlate the observation that the primordial germ cells
      may be able to undergo normal spermatogenesis in an adult recipient testis.

PMID- 11315963
TI  - Ultrastructural features of rat arcuate nucleus neurons during pregnancy.
AB  - The ultrastructure of the arcuate nucleus was studied in Sprague-Dawley rats
      sacrificed at 7, 10, 14 and 20 days of gestation, using conventional techniques
      of electron microscopy. Our results revealed an increase in granular filamentous
      bodies and whorled bodies that appear in arcuate neurons as early as on the 7th
      day of gestation. A further increase of these structures was showed by day 10
      and, especially, by day 14. In the arcuate nucleus of rats sacrificed on day 14
      of gestation, some compact, homogeneous and very large (up to 5.5 microm
      diameter) granular filamentous bodies may be seen both in neuronal bodies and in
      dendrites. In some neurons of arcuate nucleus of these gestational phases (days
      10 and 14), besides the whorled bodies dense-core vesicles were found. Neurons
      with cilia were occasionally observed, and some neuronal bodies were in close
      apposition and joined by intercellular bridges. Open synapses were observed
      during all the gestational phases. The smallest number of these synapses was seen
      in the arcuate nucleus of rats sacrificed on day 14 of gestation.

PMID- 11315964
TI  - Evidence of direct neural regulation of the anterior hypophysis reproductive
      functions.
AB  - It is generally acknowledged that the anterior hypophysis is not directly
      regulated by neural elements. Our studies in the past decade, however, have
      demonstrated otherwise. The anterior pituitary gland has been found to be
      actually under neural-humoral dual regulation. The present article outlines the
      main data that have led us to this conclusion. Evidence that is related to direct
      neural regulation of the reproductive functions of the anterior hypophysis is
      provided in great detail. Thus, synapses have been demonstrated between the nerve
      fibers innervating the anterior pituitary gland and the gonadotropes and
      lactotropes. Furthermore, there is ultrastructural evidence indicating that
      synaptic activities may induce secretion of the gland cells. Hormone manipulation
      study shows that following ovariectomy there is a significant increase of nerve
      fibers in the anterior pituitary gland, which is related to plasma estrogen
      level.

PMID- 11315965
TI  - Lymphatics of the rat mammary gland during virgin, pregnant, lactating and post
      weaning periods.
AB  - The distribution and ultrastructure of the lymphatics of the rat mammary gland in
      virgin, pregnant, lactating and post-weaning periods were examined by enzyme
      histochemistry for 5'-nucleotidase (5'-Nase) and transmission electron
      microscopy. Enzyme-histochemistry for 5'-Nase stained lymphatics in dark brown.
      In the lactating period, lymphatics abounded in the interlobular connective
      tissues, but in other periods they were few. The interlobular lymphatics drained
      into collecting lymphatics running along the mammary ducts. Gaps between
      lymphatic endothelial cells were significantly wider in lactating period than in
      other periods, while both number and area of vesicles in the lymphatic
      endothelial cells were significantly larger in the virgin period than in other
      periods. In the pregnant and lactating period, the lymphatics contained many
      lymphocytes and lipid droplets. The results show that during lactating period,
      the interlobular lymphatics increase and that gaps between lymphatic endothelial
      cells serve as a major route through which tissue fluids and particulate matters
      enter the lymphatics, while vesicles seem to be main trans-endothelial transport
      route during the virgin period. The results will provide basic information for
      our next investigation on lymphangiogenesis in association with breast cancer.

PMID- 11315966
TI  - Postmenopausal osteoporosis: microradiographic aspects.
AB  - A comparative microradiographic and histologic analysis of undecalcified bone
      samples was performed in men and women aged 18-98 years. These morphological
      methods showed that besides usual lamellar bone remodelling, all the so-called
      inert surfaces, namely both haversian and vascular canals as well as trabecular
      surfaces, were involved in weathering alterations of the superficial lamellae,
      resulting in eroded outlines devoid of osteoclast. These aspects, recorded in all
      pieces of our material, were visible from the earliest adult age and were
      randomly distributed. Except the grade of osteoporosis at a given age, the
      microradiographic and histologic aspects were similar in both aged men and women
      and did not allow sex distinction. These observations were consistent with the
      hypothesis of a particular destructive process affecting all the quiescent
      lamellar bone surfaces without osteoclast or cell participation. This kind of
      erosion, termed delitescence, could be at least partially responsible for the age
      related and postmenopausal bone loss. In order to explain the increasing
      osteoporosis after menopause, it has been suggested that the estrogen deficiency
      could increase the percentage of dead osteocytes. Thereby the reduced cellular
      control on the bone surface could impair the remodeling process and fail to adapt
      the bone structure by repairing the microscopic lesions.

PMID- 11315967
TI  - Morphological and cytochemical study of extracellular matrix during the migratory
      phase of human and mouse primordial germ cells.
AB  - Primordial germ cells (PGCs), the ancestors of functional gametes in mammals,
      originate in an extragonadal location, and then migrate to and colonize the
      genital ridges during early organogenesis period. PGCs move actively from their
      original site, the wall of the hindgut, through the extracellular matrix (ECM) of
      the dorsal mesentery. This movement is controlled in part by components of the
      ECM. Cells are known to bind to individual ECM glycoproteins in a complex and
      poorly understood way. During migration in embryos, PGCs must alter their overall
      adhesiveness to the endodermal epithelium to allow locomotion. This study
      examined the ECM material of the migratory route during mouse and human PGCs
      migration. Mouse embryos obtained from Swiss Rockefeller mouse and normal human
      embryos between 4 and 7 weeks of development, collected during salpingectomy
      performed on patients with tubal ectopic pregnancies, were analyzed. The study
      was based on a morphological analysis using scanning electron microscopy (SEM),
      and on the histochemical and ultracytochemical identification of
      glycosaminoglycans (GAGs) and proteoglycans. In each age group, the mesenchyme
      was widely separated by intercellular spaces and materials. Fine filamentous
      strands extended between the surface of mesenchymal cells and the surface of
      PGCs. Hyaluronan and chondroitin and/or dermatan sulfate were localized in the
      ECM of the PGC migratory pathway both in mouse and human embryos. Hyaluronan was
      clearly reduced in the later stage of the migratory processes; on the contrary,
      the chondroitin sulfate reaction product increased. These results are consistent
      with previous observations showing that hyaluronan is a major component of the
      ECM, and are also suggestive of the significant role played by hyaluronan,
      chondroitin sulfate and dermatan sulfate during migration, thus providing a
      permissive substrate for cell migration during development. The observed temporal
      and regional patterns suggest that these GAGs are important morphogenetic factors
      both in the mouse and human although the precise biological function of the
      proteoglycans are not currently clear.

PMID- 11315968
TI  - A morphometric approach to the study of human ovarian organogenesis.
AB  - This study deals with the morphometric approach used to describe the quantitative
      characteristics of human ovaries during their final histogenesis. Fixed ovaries
      ranging from the 20th fetal week to the 8th postnatal month were used. They were
      measured using a high precision caliper, were embedded in toto in epoxide resin,
      and systematically cut (1 microm-thick sections) orthogonal to the major axis of
      the organ. The surface areas were automatically measured, at low magnification,
      and ovarian volume was calculated using the Cavalieri method. The volume
      fractions of ovarian medulla, primitive cortical tissue, primordial, primary,
      secondary and Graafian follicles, and stroma were calculated by differential
      point counting at higher magnification. At the same magnification, the position
      of the different follicle categories in the cortex was estimated as percentage
      distance of the follicle from the cortico-medullary boundary. The number in unit
      cortex volume of the oocyte nuclei in primordial and primary follicles were
      derived by diameter analysis according to the Schwartz-Saltykov method, and the
      total follicle number for each ovary was obtained. The diameter of nuclear,
      cellular and follicular profiles of primary and primordial follicles in sections
      was also measured. Ovarian volume was about 30 mm3 at 20 fetal weeks and 287 mm3
      at the 8th postnatal month, with a 9.5-fold increment. Irrespective of age, the
      cortex occupied most of the organs, ranging from 90% at 20 prenatal weeks (about
      27 mm3) to 85% at 8 postnatal months (about 245 mm3). In the cortex, the
      interstitium or stroma intermingled with the germinal component: primitive
      cortical tissue was found in all ovaries, and its absolute volume remained
      unmodified between the 20th fetal week and birth. In the analyzed fetal stages,
      the total number of primordial follicles had its largest modification, with a 1.3
      fold increment between the 20th-25th fetal weeks. Hereafter, the number increased
      at a slower rate (about 1.2 times between the 25th week and birth, 1.1 times
      between birth and the 8th postnatal month). The largest absolute volume of
      primordial follicles was found at birth. Follicular, oocyte and nuclear diameters
      increased during the intrauterine life, while after birth their dimensions did
      not modify further. Conversely, their spatial position in the cortex modified
      even after birth. In the 8-month old child nearly all germinal cells were
      comprised into follicles in different degrees of development, and the primitive
      cortical tissue was exhausted. A three-dimensional geometrical model of human
      ovary has also been elaborated to define the spatial organization of ovarian
      germinal and somatic components, and to allow the comparison of the present data
      to the "in-vivo" volumetric assessments.

PMID- 11315969
TI  - Electron microscopic in situ hybridization study of simultaneous expression of
      TNP1 and PRM1 genes in human spermatids.
AB  - Nuclear changes in the basic nucleoprotein complement occur during human
      spermiogenesis. Somatic type histones are displaced by transition proteins which
      are replaced themselves by protamines, the major nuclear proteins found in late
      spermatids and spermatozoa nuclei. Digoxigenin or Biotin labeled probes, coding
      respectively for human transition protein 1 (TP1) and protamine 1 (HP1), were
      used for double EM in situ hybridization. Immunodetection of hybrids with
      specific antibodies coupled to colloidal gold particles of different size (10 nm
      and 15 nm) was performed on the same preparations. Quantitative analysis of the
      nuclear and cytoplasmic labeling densities for the mRNAs coding for TP1 and HP1
      showed the presence of transcripts in both the nucleus and cytoplasm of round
      spermatids until the elongation phase. Transcripts accumulated in the spermatid
      cytoplasm without any particular cellular compartmentalization. At the end of the
      spermatid elongation phase, the disappearing of TP1 and HP1 transcripts may be
      related to the arrest of transcriptional activity while the deposition of
      transition proteins and protamines successively occurs within spermatid nuclei.

PMID- 11315970
TI  - Evaluation of human sperm acrosome reaction and viability by flow cytometry.
AB  - We report in this work a quantitative procedure developed to evaluate the
      acrosomal reaction and vitality of human spermatozoa, with three color staining
      simultaneously. Twenty normal human sperm were labeled with GB24 monoclonal
      antibody, a fluorescein isothiocyanate conjugated lectin and propidium iodide
      (supravital stain). Four conjugated lectins were investigated: WGA, Con-A, PNA
      and UEA-1. Acrosome reaction was induced with calcium ionophore A-23187. Analyses
      were made by flow cytometry and electron microscopy. A high percentage of
      spermatozoa that stained with propidium iodide was found. The results of four
      lectins show an interaction between GB24 and lectin binding. Significant
      differences of fluorescence index were obtained between the samples with calcium
      ionophore A-23187 and the samples without it. The WGA-GB24 association shows an
      independent behavior and this may depend on the fact that WGA binds to the
      cytoplasmic membrane of human spermatozoa and GB24 antibody bind inner acrosome
      membrane. Using Con-A, PNA and UEA-I a crowded staining is likely to occur
      because these lectins and GB24 antibody mainly bind to acrosome membranes, and
      our results then show a close relation.

PMID- 11315971
TI  - Egg-sperm interactions in humans: ultrastructural aspects.
AB  - A large cumulus mass usually covers the human ovulated oocyte, and voluminous
      clusters of cumulus cells are still seen after fertilization around the egg.
      Cumulus cells surround oocytes and fertilized eggs also during in vitro
      fertilization (IVF) procedures. This study describes, by transmission and
      scanning electron microscopy, the morphology and the microtopography of the cells
      forming the human cumulus mass surrounding IVF samples (insemined but not
      fertilized oocytes and fertilized eggs). Particularly emphasized is their
      morphodynamic role in sperm-egg interactions. A comparison with the behavior in
      vivo of cumulus-enclosed oocyte/fertilized eggs has been also performed. All
      patients have given their informed consent to participate in this protocol. An
      inner layer (corona radiata cells) and an outer layer (proper cumulus cells) can
      be microtopographically recognized in the cumulus mass. Numerous cumulus-corona
      cells, particularly after fertilization, showed ultrastructural characteristics
      typical for steroid synthetic cells, thus undergoing a sort of "luteinization"
      parallel to that occurring in the sister granulosa cells of the postovulatory
      follicle. This steroid synthetic activity, particularly enhanced in vitro but
      present also in vivo, may be finalized to the release of small amount of steroids
      (estrogens and progesterone) in the oocyte/fertilized egg milieu. Various
      proteins, secreted by other cell subpopulations--as revealed in other studies by
      our research group--, may even enrich this milieu. Lymphocytes and macrophages
      were often found in the cumulus mass. They may modulate the steroid secretion of
      the neighboring cumulus cells by production of cytokines, mimicking what occurs
      in the ovarian follicle and, later, in the corpus luteum. Spermatozoa, both
      normal (acrosome-intact or--reacted) and abnormal, were frequently seen in the
      cumulus mass, free in the intercellular spaces or close to the cumulus cells,
      that can induce sperm capacitation and acrosome reaction. Leukocytes and
      cumuluscorona cells appeared both capable of actively phagocytizing supernumerary
      and/or abnormal sperms. Such spermiophagic response is present in a lesser extent
      around oocytes and eggs fertilized in vivo. In vitro, instead, cumulus
      spermiophagy leads to the elimination of a large part of the excess spermatozoa
      that have reached the oocyte, thus restoring in an extracorporeal medium the
      spermiophagic activity physiologically exerted by leukocytes and epithelial cells
      in the female and male genital tracts. In conclusion, the cumulus mass
      surrounding oocytes and fertilized eggs appears as a highly dynamic system, in
      which various subpopulations of cells cooperate in order to provide a suitable
      and healthy microenvironment for fertilization and early embryo development.

PMID- 11315972
TI  - Long-term visual outcome in patients with anterior visual pathway gliomas.
AB  - OBJECTIVES: To investigate the visual outcomes of patients with gliomas of the
      anterior visual pathway and the clinical features associated with prognosis.
      MATERIALS AND METHODS: During retrospective review, demographic and clinical data
      were abstracted from medical records of patients seen at the Bascom Palmer Eye
      Institute between January 1, 1970 and December 31, 1998. RESULTS: Of the 42
      patients identified, 68% were female, and 55% had neurofibromatosis (NF) type I.
      There was no substantial difference in presenting signs, symptoms, and visual
      acuity between the NF(+) and NF(-) groups except for nystagmus, which was more
      common in the NF(-) group (p = 0.014). Throughout follow-up evaluation, vision in
      the better eye remained stable in both groups, independent of treatment or NF
      status. Vision in the worse eye often declined, despite treatment. However,
      binocular visual status, measured as average weighted logMAR (MAR, minimum angle
      of resolution) vision, did not change significantly over time, regardless of
      treatment or NF status. CONCLUSIONS: In the NF(+) and NF(-) groups, vision in the
      better eye remained stable, regardless of treatment, and vision in the worse eye
      often declined, despite treatment. Binocular visual acuity (measured as weighted
      logMAR) did not change significantly over time, regardless of NF status or
      treatment modality.

PMID- 11315973
TI  - Epidemiology of idiopathic intracranial hypertension in Israel.
AB  - OBJECTIVES: To determine the incidence, demographic, and clinical features of
      Pseudo Tumor Cerebri (PTC)/Idiopathic Intracranial Hypertension (IIH) in Israel.
      MATERIALS AND METHODS: The chairpersons of all neurology and ophthalmology
      departments in Israel were asked to complete questionnaires regarding patients
      diagnosed with PTC/IIH from 1998 through 1999. Each questionnaire contained
      details regarding patient's age, sex, country of birth, age at diagnosis, weight,
      height, presence of obesity, and the results of lumbar puncture, brain computed
      tomography, magnetic resonance imaging, and/or magnetic resonance venography.
      RESULTS: Ninety-one patients with PTC/IIH were diagnosed during the years 1998 to
      1999. Eighty-five (93.4%) patients were females and six (6.6%) patients were
      males. The calculated incidence of PTC/IIH in the Israeli general population was
      0.57 to 0.94 per 100,000 persons, with incidences of 1.82 per 100,000 for women
      and 0.034 per 100,000 for men. The incidence for women during the childbirth
      years was 4.02 per 100,000. The female to male ratio was higher than previously
      reported for Western countries. CONCLUSIONS: Although the population of Israel is
      a mixture of people originating from Eastern and Western countries, the incidence
      of PTC/IIH was found to be similar to that of Western countries. This finding is
      an additional support to the notion that PTC/IIH is more common in obese
      populations.

PMID- 11315974
TI  - Do men with pseudomotor cerebri share the same characteristics as women? A
      retrospective review of 141 cases.
AB  - OBJECTIVE: To determine whether males with pseudotumor cerebri (PTC) differ from
      females by clinical presentation, risk factors, and outcome. METHODS: The medical
      records of patients diagnosed with PTC or idiopathic intracranial hypertension
      (IIH) in two major university hospitals were obtained. Diagnostic criteria,
      clinical features, presence of obesity, mode of treatment, and outcome were
      tabulated. RESULTS: A total of 134 patients (18 males and 116 females) fulfilled
      the Dandy diagnostic criteria for PTC. Females and males shared similar clinical
      features and outcome. There was a substantial difference between the groups
      regarding body weight. The majority of females (77.8%) were considered
      significantly overweight, compared to 25% of the males. CONCLUSION: Pseudotumor
      cerebri in males is relatively rare. The clinical features are identical to those
      found in females. The fact that the majority of the male patients had a normal
      body weight may indicate that increased body weight does not play a major role in
      causing PTC in men, whereas it is an established major risk factor in women.

PMID- 11315975
TI  - Reversible blindness resulting from optic chiasmitis secondary to systemic lupus
      erythematosus.
AB  - OBJECTIVE: To report the diagnosis, radiologic findings, and therapy of a 51-year
      old female with systemic lupus erythematosus (SLE) who, while on
      hydroxychloroquine maintenance therapy, presented with a junctional scotoma
      indicative of chiasmal disease. This visual loss developed after she had been
      tapered off corticosteroids. MATERIALS AND METHODS: An interventional case report
      of a female that was given acute therapy with 1-gram daily of intravenous
      methylprednisolone sodium succinate for 5 days, followed by maintenance
      methotrexate and a slow taper of oral prednisone. Magnetic resonance imaging
      (MRI) scans, visual acuity, color vision, and threshold visual fields were
      performed. RESULTS: The MRI scan showed chiasmal involvement, which may occur in
      SLE in absence of any other evidence of systemic activity. Therapy led to visual
      function returning to 20/20 OD and 20/20 OS, with normal Ishihara plates OU and
      only minimal paracentral depressions OU. She has been able to be weaned off
      prednisone while on methotrexate maintenance. CONCLUSIONS: Chiasmal involvement
      may occur in SLE in absence of any other evidence of systemic activity.
      Maintenance with hydroxychloroquine may not be adequate to prevent this rare
      cause of visual loss in SLE. Aggressive therapy of chiasmal involvement in SLE,
      even when the visual loss is profound, may lead to visual restoration, which was
      virtually complete in this case. Methotrexate may be an alternate agent for
      patients who break through with optic neuropathy while on hydroxychloroquine.

PMID- 11315976
TI  - Anterior ischemic optic neuropathy associated with viagra.
AB  - A 42-year-old male presented with acute onset of an inferior visual field defect
      OD after sildenafil citrate use. Examination revealed a right relative afferent
      pupillary defect and a swollen disc with a 0.1 cup-to-disc ratio and a prominent
      disc hemorrhage. Anterior ischemic optic neuropathy (AION) is associated with
      acute episodes of hypotension in patients with structurally crowded discs.
      Sildenafil citrate may cause episodes of hypotension and was temporally related
      to the onset of symptoms in this patient. Because patients are often reluctant to
      volunteer their history of sildenafil citrate use, the physician may need to ask
      specifically about use of this medication. Physicians should counsel patients
      with crowded optic discs and a history of nonarteritic anterior ischemic optic
      neuropathy in one eye that use of sildenafil citrate might increase their risk of
      ischemic optic neuropathy in the fellow eye.

PMID- 11315977
TI  - A girl without a chiasm: electrophysiologic and MRI evidence for the absence of
      crossing optic nerve fibers in a girl with a congenital nystagmus.
AB  - An otherwise healthy 15-year-old girl with a congenital nystagmus was evaluated
      at our department using visual evoked potential recording and magnetic resonance
      imaging. She appears to have the unique isolated inborn absence of the optic
      chiasm, described only once before in two unrelated girls. Unlike these
      previously described cases, our patient does not seem to display a see-saw
      nystagmus.

PMID- 11315978
TI  - Autoenucleation of a blind eye.

PMID- 11315979
TI  - Rapid recovery with oral zinc sulphate in deferoxamine-induced presumed optic
      neuropathy and hearing loss.

PMID- 11315980
TI  - Granulomatous hypophysitis and bilateral optic neuropathy.
AB  - A 53-year-old woman with symptoms of hypopituitarism and ophthalmoplegia was
      diagnosed as having idiopathic granulomatous hypophysitis and later developed
      bilateral optic neuritis. She responded well to steroid treatment. Granulomatous
      hypophysitis is a rare entity, and this is the first reported case associated
      with optic neuritis.

PMID- 11315981
TI  - Increased endothelin-1 plasma levels in patients with multiple sclerosis.
AB  - OBJECTIVE: We tested the hypothesis that the plasma level of endothelin-1 (ET-1)
      is increased in patients with multiple sclerosis (MS). The peptide ET-1 is one of
      the most potent known vasoconstrictors. An increased level of endothelin could
      explain some of the vascular symptoms of these patients. MATERIALS AND METHODS: A
      specific radioimmunoassay was used to determine ET-1 plasma levels. Twenty
      patients with MS were compared to 20 age- and sex-pair-matched healthy subjects.
      RESULTS: The plasma ET-1 levels were, on average, 224% higher in the patients
      with MS than in the controls (p < 0.005). The mean ET-1 levels (mean +/- standard
      deviation [SD]) were 3.5 +/- 0.83 pg/mL (min 2.13, max 5.37 pg/mL) in patients
      with MS and 1.56 +/- 0.3 pg/mL (min 0.9, max 2.13 pg/mL) in healthy volunteers.
      Neither the different forms nor stages of MS had an influence on the results. The
      ET-1 level was also not correlated with the duration of the disease. CONCLUSIONS:
      The plasma ET-1 level is markedly and significantly increased in patients with
      MS. Neither the cause of such an increase nor the pathogenetic role is known.

PMID- 11315982
TI  - Comparison of clinical associations of patients with vasculopathic and idiopathic
      downbeat nystagmus.
AB  - OBJECTIVES: To perform a pilot study comparing age and vascular risk factors of
      patients with vasculopathic and idiopathic downbeat nystagmus (DBN). MATERIALS
      AND METHODS: We reviewed the case records of 57 patients with DBN evaluated
      between 1987 and 1999, and classified each patient into three groups:
      vasculopathic, idiopathic, and other known causes. We then compared age and five
      weighted established stroke risk factors in patients with vasculopathic and
      idiopathic DBN. RESULTS: Of ten idiopathic cases, there were seven women and
      three men, ranging in age from 31 to 90 years (median, 79 years). Of the nine
      vasculopathic cases, there were seven women and two men, ranging in age from 50
      to 86 years (median, 80 years). Using the Mann-Whitney U test, there was no
      significant difference between the two groups in terms of age (p = 0.84) or
      vascular risk-factor profile (p = 0.24). CONCLUSIONS: The lack of significant
      difference between the two groups for age and vascular risk factors supports the
      hypothesis that some idiopathic cases of DBN may be caused by strategically
      located and radiographically occult cerebral infarctions.

PMID- 11315983
TI  - Pattern visual evoked potentials in malingering.
AB  - OBJECTIVES: We previously developed a new method for estimating objective visual
      acuity by means of pattern visual evoked potentials (PVEP). In this study, this
      method was applied to the diagnosis of malingering. MATERIALS AND METHODS: Six
      patients ranging in age from 40 to 54 years (mean 47 years) with suspected
      malingering were evaluated by means of the visual evoked potential test,
      optokinetic nystagmus (OKN) inhibition test, and the visual field test. In the
      PVEP study, the stimulus consisted of black and white checkerboards (39', 26',
      15', and 9') with a visual angle of 8 degrees, contrast level of 15%, and a
      frequency of 0.7 Hz. One hundred PVEP responses were averaged per session.
      RESULTS: Routine ophthalmic examinations were normal in all patients. Five
      patients had a tubularly constricted visual field, and the remaining patient had
      a normal visual field. The objective visual acuities of the six patients
      estimated from PVEP were better than their subjective visual acuities estimated
      with Landolt rings. CONCLUSIONS: Among a variety of psychophysical and
      electrophysiologic ancillary tests, we consider our PVEP method a useful method
      for objectively determining visual acuity in a patient with signs of ocular
      malingering.

PMID- 11315984
TI  - Systemic disease and neuro-ophthalmology: annual update 2000 (Part I).

PMID- 11315985
TI  - Functional and morphologic comparison of two methods to produce transient retinal
      ischemia in the rat.
AB  - OBJECTIVES: Much of our knowledge of the pathophysiology of retinal ischemic
      injury is from a multitude of studies that use in vitro or in vivo animal models
      of retinal ischemia followed by reperfusion. The objective of this study was to
      compare histopathologic and electrophysiologic (electroretinography) parameters
      using two different models of transient retinal ischemia: high intraocular
      pressure (HIOP) and suture ligation of the optic nerve (SL). METHODS: Transient
      retinal ischemia was induced using the HIOP model or the SL model in the Sprague
      Dawley rat for either 30 or 60 minutes. Histopathologic outcome was determined at
      1 and 7 days after ischemia. In addition, electroretinography (ERG) was performed
      at 2 hours, I day, 3 days, and 7 days after ischemia. RESULTS: At 1 and 7 days
      after 30 minutes of ischemia, there were no significant histopathologic
      abnormalities in the retina with either model, except for a slight decrease of
      the cell count in the ganglion cell layer (GCL) with the SL method. After 60
      minutes of ischemia, there was significant thinning of the inner retina. There
      was a significant early dropout of cells at 1 day in the inner nuclear layer
      (INL) in the HIOP method compared to the SL method where the dropout was delayed
      and gradually progressive. Dropout of cells in the GCL was early (I day) and
      gradually progressive in both models but more severe in HIOP than SL. There was a
      significant decrease in the ERG b-wave amplitudes as early as 2 hours after both
      30 and 60 minutes of ischemia compared to preischemic baselines. CONCLUSIONS: The
      degree of retinal injury after transient retinal ischemia was more severe at 1
      day after reperfusion in the HIOP method compared to the SL method but was
      similar at 7 days in both models. Furthermore, our data suggests that functional
      assessment of ischemic damage by electroretinography may be a more sensitive
      parameter than conventional histopathologic quantification. The timing of either
      measurement relative to the ischemic stimulus is critical because histologic
      measurements performed too early after ischemia may underestimate the degree of
      injury.

PMID- 11315986
TI  - Visual activation in functional magnetic resonance imaging at very high field (4
      Tesla).
AB  - OBJECTIVES: Functional magnetic resonance imaging (fMRI) at very high field
      strengths provides functional brain mapping with the enhanced signal to noise
      ratio and the larger blood oxygenation level-dependent (BOLD) effect. We report
      activated areas in the standard space detected by fMRI at 4 Tesla (T) during
      simple visual stimulation. MATERIALS AND METHODS: Twelve healthy young subjects
      were scanned using a 4 T scanner during binocular flashing visual stimulation.
      Functional images were realigned to the first scan and then spatially normalized.
      Individual and group data analyses were performed to identify areas of visual
      activation. RESULTS: Activation of the bilateral primary visual cortex (V1/V2)
      was observed along the entire calcarine fissure in all subjects. The activated
      area extended to the extrastriate cortex in all subjects. Activation of the
      bilateral lateral geniculate nucleus (LGN) was detected in all subjects. The
      group data showed activation of the bilateral primary visual cortex and the
      bilateral lateral geniculate nucleus. CONCLUSIONS: Robust activation of the
      vision-related areas was successfully obtained in all subjects using a 4 T
      magnetic resonance scanner. These results suggest that fMRI at very high field
      strengths may be effective in showing visual system physiology, and that it can
      be a promising method to assess visual function of human subjects.

PMID- 11315987
TI  - Changes in bone density during childhood and adolescence: an approach based on
      bone's biological organization.
AB  - Bone densitometry has great potential to improve our understanding of bone
      development. However, densitometric data in children rarely are interpreted in
      light of the biological processes they reflect. To strengthen the link between
      bone densitometry and the physiology of bone development, we review the
      literature on physiological mechanisms and structural changes determining bone
      mineral density (BMD). BMD (defined as mass of mineral per unit volume) is
      analyzed in three levels: in bone material (BMD(material)), in a bone's
      trabecular and cortical tissue compartments (BMD(compartment)), and in the entire
      bone (BMD(total)). BMD(material) of the femoral midshaft cortex decreases after
      birth to a nadir in the first year of life and thereafter increases. In iliac
      trabecular bone, BMD(material) also increases from infancy to adulthood,
      reflecting the decrease in bone turnover. BMD(material) cannot be determined with
      current noninvasive techniques because of insufficient spatial resolution.
      BM(compartment) of the femoral midshaft cortex decreases in the first months
      after birth followed by a rapid increase during the next 2 years and slower
      changes thereafter, reflecting changes in both relative bone volume and
      BMD(material). Trabecular BMD(compartment) increases in vertebral bodies but not
      at the distal radius. Quantitative computed tomography (QCT) allows for the
      determination of both trabecular and cortical BMD(compartment), whereas
      projectional techniques such as dual-energy X-ray absorptiometry (DXA) can be
      used only to assess cortical BMD(compartment) of long bone diaphyses. BMD(total)
      of long bones decreases by about 30% in the first months after birth, reflecting
      a redistribution of bone tissue from the endocortical to the periosteal surface.
      In children of school age and in adolescents, changes in BMD(total) are site
      specific. There is a marked rise in BMD(total) at locations where relative
      cortical area increases (metacarpal bones, phalanges, and forearm), but little
      change at the femoral neck and midshaft. BMD(total) can be measured by QCT at any
      site of the skeleton, regardless of bone shape. DXA allows the estimation of
      BMD(total) at skeletal sites, which have an approximately circular cross-section.
      The system presented here may help to interpret densitometric results in growing
      subjects on a physiological basis.

PMID- 11315988
TI  - Development of a novel immunoradiometric assay exclusively for biologically
      active whole parathyroid hormone 1-84: implications for improvement of accurate
      assessment of parathyroid function.
AB  - We developed a novel immunoradiometric assay (IRMA; whole parathyroid hormone
      [PTH] IRMA) for PTH, which specifically measures biologically active whole PTH(1
      84). The assay is based on a solid phase coated with anti-PTH(39-84) antibody, a
      tracer of 125I-labeled antibody with a unique specificity to the first N-terminal
      amino acid of PTH(1-84), and calibrators of diluted synthetic PTH(1-84). In
      contrast to the Nichols intact PTH IRMA, this new assay does not detect PTH(7-84)
      fragments and only detects one immunoreactive peak in chromatographically
      fractionated patient samples. The assay was shown to have an analytical
      sensitivity of 1.0 pg/ml with a linear measurement range up to 2,300 pg/ml. With
      this assay, we further identified that the previously described non-(1-84)PTH
      fragments are aminoterminally truncated with similar hydrophobicity as PTH(7-84),
      and these PTH fragments are present not only in patients with secondary
      hyperparathyroidism (2 degrees -HPT) of uremia, but also in patients with primary
      hyperparathyroidism (1 degrees -HPT) and normal persons. The plasma normal range
      of the whole PTH(1-84) was 7-36 pg/ml (mean +/- SD: 22.7 +/- 7.2 pg/ml, n = 135),
      whereas over 93.9% (155/165) of patients with 1 degrees -HPT had whole PTH(1-84)
      values above the normal cut-off. The percentage of biologically active whole
      PTH(1-84) (pB%) in the pool of total immunoreactive "intact" PTH is higher in the
      normal population (median: 67.3%; SD: 15.8%; n = 56) than in uremic patients
      (median:53.8%; SD: 15.5%; n = 318; p < 0.001), although the whole PTH(1-84)
      values from uremic patients displayed a more significant heterogeneous
      distribution when compared with that of 1 degrees -HPT patients and normals.
      Moreover, the pB% displayed a nearly Gaussian distribution pattern from 20% to
      over 90% in patients with either 1 degrees-HPT or uremia. The specificity of this
      newly developed whole PTH(1-84) IRMA is the assurance, for the first time, of
      being able to measure only the biologically active whole PTH(1-84) without cross
      reaction to the high concentrations of the aminoterminally truncated PTH
      fragments found in both normal subjects and patients. Because of the significant
      variations of pB% in patients, it is necessary to use the whole PTH assay to
      determine biologically active PTH levels clinically and, thus, to avoid
      overestimating the concentration of the true biologically active hormone. This
      new assay could provide a more meaningful standardization of future PTH
      measurements with improved accuracy in the clinical assessment of parathyroid
      function.

PMID- 11315989
TI  - Increased vitamin D receptor level enhances 1,25-dihydroxyvitamin D3-mediated
      gene expression and calcium transport in Caco-2 cells.
AB  - Altered vitamin D receptor (VDR) level has been proposed to explain differences
      in intestinal responsiveness to 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. We tested
      whether the enterocyte VDR level influences 1,25(OH)2D3-mediated gene expression
      and transepithelial calcium (Ca) transport in the human intestinal cell line Caco
      2. Cells were stably transfected with a human metallothionein (hMT) IIA promoter
      human VDR (hVDR) complementary DNA (cDNA) transgene that overexpressed hVDR in
      response to heavy metals. In MTVDR clones, induction of 25-hyroxyvitamin D3-24
      hydroxylase (24-OHase) messenger RNA (mRNA) expression by 1,25(OH)2D3 (10(-9) M,
      4 h) was correlated to metal-induced changes in nuclear VDR level (r2 = 0.99). In
      MTVDR clones, basal VDR level was 2-fold greater and 1,25(OH)2D3-mediated Ca
      transport (10(-7) M, 24 h) was 43% higher than in parental Caco-2 cells.
      Treatment of MTVDR clones with Cd (1 microM, 28 h) increased VDR level by 68%,
      significantly enhanced 1,25(OH)2D3-mediated Ca transport by 24%, and increased
      accumulation of calbindin D9K mRNA by 76% relative to 1,25(OH)2D3 alone. These
      observations support the hypothesis that the enterocyte VDR level is an important
      modulator of intestinal responsiveness to 1,25(OH)2D3.

PMID- 11315990
TI  - Interaction of two novel 14-epivitamin D3 analogs with vitamin D3 receptor
      retinoid X receptor heterodimers on vitamin D3 responsive elements.
AB  - This study provides a detailed and exact evaluation of the interactions between
      vitamin D3 receptor (VDR), retinoid X receptor (RXR), and vitamin D3 responsive
      elements (VDREs) mediated by two novel 14-epianalogs of 1,25-dihydroxyvitamin D
      [1,25(OH)2D3], 19-nor-14-epi-23-yne-1,25(OH)2D3 (TX 522) and 19-nor-14,20-bisepi
      23-yne-1,25(OH)2D3 (TX 527). Both analogs were more potent (14- and 75-fold,
      respectively) than 1,25(OH)2D3 in inhibiting cell proliferation and inducing cell
      differentiation. However, DNA-independent experiments indicated that both analogs
      had a lower affinity to VDR and that the stability of the induced VDR
      conformation, as measured by limited protease digestion assays, was similar (TX
      527) or even weaker (TX 522) than that induced by the parent compound. However,
      DNA-dependent assays such as gel shift experiments revealed that those analogs
      were slightly more potent (3-7 times) than 1,25(OH)2D3 in enhancing binding of
      VDR-RXR heterodimers to a direct repeat spaced by three nucleotides (DR3) type
      VDRE. The functional consequences of the ligand-VDR-RXR-VDRE interactions
      observed in vitro were subsequently evaluated in transfection experiments. Both
      14-epianalogs enhanced transcription of VDRE containing reporter constructs more
      efficiently than 1,25(OH)2D3 in COS-1 and MCF-7 cells regardless of the presence
      of ketoconazole. Transactivation activity is suggested to be a cell-specific
      process because maximal transcriptional induction and the half-maximal
      transactivation concentration for each reporter construct were different in both
      cell lines. The superagonistic transactivation activity closely resembled the
      biological potency of these analogs on the inhibition of MCF-7 cell
      proliferation. These data clearly indicate that superagonistic activity starts
      beyond the binding of the ligand-heterodimer (VDR-RXR) complex to VDRE and thus
      probably involves coactivator/corepressor molecules.

PMID- 11315991
TI  - 1alpha-hydroxyvitamin D2 is less toxic but not bone selective relative to 1alpha
      hydroxyvitamin D3 in ovariectomized rats.
AB  - Identification of bone selective vitamin D analogues would provide an interesting
      substance class for the treatment of osteoporosis. The synthetic prodrug 1alpha
      hydroxyvitamin D2 [1alpha(OH)D2] has been shown to combine equal bone-preserving
      activity with distinctly reduced calcemic effects relative to 1alpha
      hydroxyvitamin D3 [1alpha(OH)D3] in 3-month-old ovariectomized (OVX) rats.
      Therefore, 1alpha(OH)D2 may be a bone-selective compound. The aim of this study
      was to compare the bone protective and the calcemic activities of chronically
      administered 1alpha(OH)D2 and 1alpha(OH)D3 in 6-month-old OVX rats over a broad
      dose range from ineffective to toxic doses. Ninety-six female 6-month-old Fischer
      344 rats were used for this experiment. Eighty rats were bilaterally OVX, 8 rats
      were sham-operated (SHAM), and 8 rats were killed at the time of surgery as a
      baseline control. Groups of OVX rats received vehicle alone (n = 16) or daily
      doses in the diet of 0.025, 0.05, 0.1, and 0.2 microg of 1alpha(OH)D2 or
      1alpha(OH)D3 per kg body weight (BW) per day (n = 8 each). After calcein double
      labeling, all animals were killed 3 months post-OVX. Orally administered
      1alpha(OH)D2 was significantly less toxic compared with 1alpha(OH)D3 in terms of
      BW gain and kidney calcium content. The effects of 1alpha(OH)D2 and 1alpha(OH)D3
      on serum calcium and urinary calcium excretion were generally similar at all
      doses in this study. Both 1alpha(OH)D2 and 1alpha(OH)D3 prevented the estrogen
      deficiency-induced bone loss in OVX rats, and induced profound bone anabolic
      effects at high dosages. 1alpha(OH)D3 and 1alpha(OH)D2 also dose-dependently
      increased total bone mineral density (BMD), cortical area, and cortical thickness
      in the tibial diaphysis of OVX rats. Bone resorption as assessed by osteoclast
      numbers (Oc.Ns) in vertebral cancellous bone and urinary excretion of
      deoxypyridinoline (DPD) was dose-dependently suppressed by 1alpha(OH)D2 and
      1alpha(OH)D3. These data show that although 1alpha(OH)D2 was slightly but
      significantly less toxic compared with 1alpha(OH)D3, it did not have increased
      skeletal effects at any dose. Taken together, our findings argue against
      selective metabolic activation of 1alpha(OH)D2 in bone.

PMID- 11315992
TI  - Osteopontin deficiency reduces experimental tumor cell metastasis to bone and
      soft tissues.
AB  - Osteopontin has been implicated in the metastasis of tumors, and human tumors
      with high metastatic activity often express osteopontin at high levels.
      Osteopontin contains an arginine-glycine-aspartate (RGD) motif that is recognized
      by integrin family members to promote various cell activities including
      attachment to substrate and it is abundant in bone, to which certain tumors
      preferentially metastasize. Therefore, we investigated the role of osteopontin in
      the experimental metastasis of tumor cells using recently established osteopontin
      deficient mice. B16 melanoma cells, which produce little osteopontin, were
      injected into the left ventricle of osteopontin-deficient mice or wild-type mice.
      Animals were killed 2 weeks after injection. The number of tumors was reduced in
      the bones of osteopontin-deficient mice compared with the bones in wild-type
      mice. The number of tumors in the adrenal gland also was reduced. To investigate
      the osteopontin effect on metastases via a different route, we injected B16
      melanoma cells into the femoral vein. Through this route, the number of lung
      tumors formed was higher than in the intracardiac route and was again less in
      osteopontin-deficient mice compared with wild-type mice. In conclusion, in an
      experimental metastasis assay, the number of tumors found in bone (after
      intracardiac injection) and lung (after left femoral vein injection) was
      significantly reduced in osteopontin-deficient mice compared with wild-type mice.
      Tumor numbers in other organs examined were small and not significantly different
      in the two situations.

PMID- 11315993
TI  - Evidence for a direct role of cyclo-oxygenase 2 in implant wear debris-induced
      osteolysis.
AB  - Aseptic loosening is a major complication of prosthetic joint surgery and is
      manifested as chronic inflammation, pain, and osteolysis at the bone implant
      interface. The osteolysis is believed to be driven by a host inflammatory
      response to wear debris generated from the implant. In our current study, we use
      a selective inhibitor (celecoxib) of cyclo-oxygenase 2 (COX-2) and mice that lack
      either COX-1 (COX-1-/-) or COX-2 (COX-2-/-) to show that COX-2, but not COX-1,
      plays an important role in wear debris-induced osteolysis. Titanium (Ti) wear
      debris was implanted surgically onto the calvaria of the mice. An intense
      inflammatory reaction and extensive bone resorption, which closely resembles that
      observed in patients with aseptic loosening, developed within 10 days of
      implantation in wild-type and COX-1-/- mice. COX-2 and prostaglandin E2 (PGE2)
      production increased in the calvaria and inflammatory tissue overlying it after
      Ti implantation. Celecoxib (25 mg/kg per day) significantly reduced the
      inflammation, the local PGE2 production, and osteolysis. In comparison with wild
      type and COX-1-/- mice, COX-2-/- mice implanted with Ti had a significantly
      reduced calvarial bone resorption response, independent of the inflammatory
      response, and significantly fewer osteoclasts were formed from cultures of their
      bone marrow cells. These results provide direct evidence that COX-2 is an
      important mediator of wear debris-induced osteolysis and suggests that COX-2
      inhibitors are potential therapeutic agents for the prevention of wear debris
      induced osteolysis.

PMID- 11315994
TI  - Low-intensity pulsed ultrasound accelerates rat femoral fracture healing by
      acting on the various cellular reactions in the fracture callus.
AB  - Low-intensity pulsed ultrasound (LIPUS) has been shown to accelerate fracture
      healing in both animal models and clinical trials, but the mechanism of action
      remains unclear. In fracture healing, various consecutive cellular reactions
      occurred until repair. We investigated whether the advanced effects of LIPUS
      depended on the duration and timing of LIPUS treatment in a rat closed femoral
      fracture model to determine the target of LIPUS in the healing process. Sixty
      nine Long-Evans male rats that have bilateral closed femoral fractures were used.
      The right femur was exposed to LIPUS (30 mW/cm2 spatial and temporal average
      [SATA], for 20 minutes/day), and the left femur was used as a control. Rats were
      divided into four groups according to timing and duration of treatment (Ph-1,
      days 1-8; Ph-2, days 9-16; Ph-3, days 17-24; throughout [T], days 1-24 after the
      fracture). Animals were killed on day 25. After radiographs and microfocus X-ray
      computed tomography (muCT) tomograms were taken, the hard callus area (HCA), bone
      mineral content (BMC) at the fracture site, and mechanical torsion properties
      were measured, and histological analysis was conducted. Interestingly, the
      maximum torque of the LIPUS-treated femur was significantly greater than that of
      the controls in all groups without any changes in HCA and BMC. The multiviewing
      of three-dimensional (3D) muCT reconstructions and histology supported our
      findings that the partial LIPUS treatment time was able to accelerate healing,
      but longer treatment was more effective. These results suggest that LIPUS acts on
      some cellular reactions involved in each phase of the healing process such as
      inflammatory reaction, angiogenesis, chondrogenesis, intramembranous
      ossification, endochondral ossification, and bone remodeling.

PMID- 11315995
TI  - Intervertebral disc disorganization is related to trabecular bone architecture in
      the lumbar spine.
AB  - Cancellous bone morphometry was investigated in the sagittal plane of lumbar
      vertebrae using histoquantitation. The aim of this study was to identify
      variations in cancellous bone architecture at increasing states of intervertebral
      disc (IVD) disorganization after age adjustment and to investigate regional
      variations within the whole vertebral body. Measurements were taken of the ratio
      of bone volume (BV) to total volume (TV), trabecular thickness (Tb.Th),
      trabecular separation (Tb.Sp), and trabecular number (Tb.N). Lumbar spines (T12
      L5) of 19 men and 8 women were removed at autopsy from an adult sample with no
      clinical history of bone-related disease or histologically identifiable bone
      disease. It was found that degeneration of the IVD becomes more common with
      increasing age. After age-adjustment, significant increases in the proportion of
      BV/TV were observed in the presence of advancing IVD disorganization. Significant
      architectural changes were observed in the anterior regions of the vertebral body
      with increases in Tb.Th and Tb.N and decreases in Tb.Sp. Minimal alterations were
      found at posterior regions. Bone loss was observed in central regions (most
      distant from the cortex) as IVD disorganization increased through reduction in
      both Tb.N and Tb.Th. The BV/TV increase in anterior areas of the centrum may be a
      response to a redistribution of load to the vertebral body periphery as a result
      of IVD disorganization. It appears that trabecular morphology is related to the
      condition of the associated IVD, rather than being the sole consequence of a loss
      of BV/TV with age. This relationship could influence the occurrence of vertebral
      body crush fracture.

PMID- 11315996
TI  - A three-dimensional simulation of age-related remodeling in trabecular bone.
AB  - After peak bone mass has been reached, the bone remodeling process results in a
      decrease in bone mass and strength. The formation deficit, the deficit of bone
      formation compared with previous resorption, results in bone loss. Moreover,
      trabeculae disconnected by resorption cavities probably are not repaired. The
      contributions of these mechanisms to the total bone loss are unclear. To
      investigate these contributions and the concomitant changes in trabecular
      architecture and mechanical properties, we made a computer simulation model of
      bone remodeling using microcomputed tomography (micro-CT) scans of human
      vertebral trabecular bone specimens. Up to 50 years of physiological remodeling
      were simulated. Resorption cavities were created and refilled 3 months later.
      These cavities were not refilled completely, to simulate the formation deficit.
      Disconnected trabeculae were not repaired; loose fragments generated during the
      simulation were removed. Resorption depth, formation deficit, and remodeling
      space were based on biological data. The rate of bone loss varied between 0.3%
      and 1.1% per year. Stiffness anisotropy increased, and morphological anisotropy
      (mean intercept length [MIL]) was almost unaffected. Connectivity density
      increased or decreased, depending on the remodeling parameters. The formation
      deficit accounted for 69-95%, disconnected trabeculae for 1-21%, and loose
      fragments for 1-17% of the bone loss. Increasing formation deficit from 1.8% to
      5.4% tripled bone loss but only doubled the decrease in stiffness. Increasing
      resorption depth from 28 to 56 microm slightly increased bone loss but
      drastically decreased stiffness. Decreasing the formation deficit helps to
      prevent bone loss, but reducing resorption depth is more effective in preventing
      loss of mechanical stiffness.

PMID- 11315997
TI  - Fractal analysis of radiographic trabecular bone texture and bone mineral
      density: two complementary parameters related to osteoporotic fractures.
AB  - Trabecular bone microarchitecture and bone mineral density (BMD) are two main
      factors related to osteoporotic fractures. Currently, however, microarchitecture
      is not evaluated. We have developed and validated a trabecular bone texture
      analysis from radiographic images. The objective was to determine if the fractal
      analysis of texture was able to distinguish osteoporotic fracture groups from
      control groups, either in vertebrae, hip, or wrist fractures, and to determine if
      this indicator and BMD were independent and complementary. In this cross
      sectional unicenter case-control population study in postmenopausal women, 107
      fracture cases were enrolled and age-matched with 197 control cases. This
      population comprised 40 vertebral fractures (with 70 controls), 30 hip fractures
      (55 controls), and 37 wrist fractures (62 controls). Hip and lumbar spine BMD
      were measured by double-energy X-ray absorptiometry. Fractal analysis of texture
      was performed on calcaneus radiographs and the result was expressed as the H
      parameter (H = 2-fractal dimension). The H parameter showed a lower value (0.679
      +/- 0.053 SD) in fracture cases versus control cases (0.696 +/- 0.030; p =
      0.007), the statistical significance persisting after adjustment for age and for
      lumbar spine (LS) or hip BMD. This result was confirmed in vertebral fractures (p
      = 0.0001) and hip fractures (p = 0.003) but not wrist fractures (p = 0.07). We
      determined the threshold between high and low H values and then the odds ratios
      (OR) of fracture for low H for BMD < or = -2.5 SD in T score and for the
      combinations of both parameters. The OR of fracture for low H was 1.6 (95% CI,
      1.1-2.6). For LS BMD < or = -2.5 SD the OR of 6.1 (3.4-10.8) shifted to 9.0 (4.0
      20.4) when we added low H and for hip BMD it shifted from 5.6 (3.3-9.4) to 8.1
      (4.0-16.8). In vertebral, hip, and wrist fracture cases the results were also
      significant. These data have shown that the fractal analysis of texture on
      calcaneus radiographs can distinguish osteoporotic fracture groups from control
      groups. This analysis and BMD provide independent and complementary information.
      These data suggest that we can improve the fracture risk evaluation by adding
      information related to microarchitecture, derived from analysis of conventional
      radiographic images.

PMID- 11315998
TI  - Increased expression of protein kinase Calpha, interleukin-1alpha, and RhoA
      guanosine 5'-triphosphatase in osteoblasts expressing the Ser252Trp fibroblast
      growth factor 2 receptor Apert mutation: identification by analysis of
      complementary DNA microarray.
AB  - Apert (Ap) syndrome is a craniofacial malformation characterized by premature
      fusion of cranial sutures (craniosynostosis). We previously showed that the
      Ser252Trp fibroblast growth factor receptor 2 (FGFR-2) mutation in Ap syndrome
      increases osteoblast differentiation and subperiosteal bone matrix formation,
      leading to premature calvaria ossification. In this study, we used the emerging
      technology of complementary DNA (cDNA) microarray to identify genes that are
      involved in osteoblast abnormalities induced by the Ser252Trp FGFR-2 mutation. To
      identify the signaling pathways involved in this syndrome, we used radioactively
      labeled cDNAs derived from two sources of cellular messenger RNAs (mRNAs) for
      hybridization: control (Co) and mutant Ap immortalized osteoblastic cells. Among
      genes that were differentially expressed, protein kinase Ca (PKC-alpha),
      interleukin-1alpha (IL-1alpha), and the small guanosine-5'-triphosphatase
      (GTPase) RhoA were increased in FGFR-2 mutant Ap cells compared with Co cells.
      The validity of the hybridization array was confirmed by Northern blot analysis
      using mRNAs derived from different cultures. Furthermore, immunochemical and
      Western blot analyses showed that mutant Ap cells displayed increased PKC-alpha,
      IL-1alpha, and RhoA protein levels compared with Co cells. Treatment of Co and Ap
      cells with the PKC inhibitor calphostin C decreased IL-1alpha and RhoA mRNA and
      protein levels in Ap cells, indicating that PKC is upstream of IL-1alpha and
      RhoA. Moreover, SB203580, a specific inhibitor of p38 mitogen-activated protein
      kinase (MAPK), and PD-98059, a specific inhibitor of MAPK kinase (MEKK), also
      reduced IL-1alpha and RhoA expression in Ap cells. These data show that the
      Ser252Trp FGFR-2 mutation in Ap syndrome induces constitutive overexpression of
      PKC-alpha, IL-1alpha, and small GTPase RhoA, suggesting a role for these
      effectors in osteoblast alterations induced by the mutation. The cDNA microarray
      technology appears to be a useful tool to gain information on abnormal gene
      expression and molecular pathways induced by genetic mutations in bone cells.

PMID- 11315999
TI  - Endogenous prostaglandin E2 and insulin-like growth factor 1 can modulate the
      levels of parathyroid hormone receptor in human osteoarthritic osteoblasts.
AB  - Subchondral bone sclerosis may be important for the onset and/or progression of
      cartilage loss/damage in human osteoarthritis (OA). OA osteoblasts are resistant
      to parathyroid hormone (PTH) stimulation, which could explain bone sclerosis via
      the inhibition of PTH-dependent catabolism. Here, we investigated the molecular
      mechanism(s) responsible for reduced PTH-dependent cyclic adenosine monophosphate
      (cAMP) synthesis in OA subchondral osteoblasts. Although cholera toxin (CTX)
      increased basal cAMP formation in these cells, it failed to stimulate PTH
      dependent cAMP synthesis, whereas pertussis toxin (PTX) did not inhibit basal
      cAMP, yet diminished PTH-dependent cAMP production. Binding of 125I-PTH indicated
      lower PTH receptor levels in OA than in normal osteoblasts (-50.5 +/- 9.5%). This
      could be attributed to either reduced expression of the PTH receptor (PTH-R) or
      altered recycling of existing pools of receptors. Reverse-transcription
      polymerase chain reaction (RT-PCR) analysis indicated decreased PTH-R messenger
      RNA (mRNA) levels in OA cells that were highly variable (ranging from -10% to 
      60%), a situation that reflects disease severity. Interestingly, OA osteoblasts
      produced more prostaglandin E2 (PGE2) than normal osteoblasts, and using
      naproxen, a cyclo-oxygenase inhibitor, increased PTH-dependent cAMP formation to
      a level similar to normal osteoblasts. Because heterologous desensitization can
      explain a decrease in PTH binding but cannot account for reduced PTH-R
      expression, we looked at the possible effect of insulin-like growth factor 1 (IGF
      1) on this parameter. Blocking IGF-1 signaling with a neutralizing receptor
      antibody increased 125I-PTH binding in both normal and OA osteoblasts.
      Conversely, treatments with IGF-1 receptor (IGF-1R) antibody only slightly
      increased the levels of PTH-R mRNA whereas the addition of IGF-1 significantly
      reduced PTH-R mRNA levels (-24.1 +/- 7.1%), yet neither PGE2 nor naproxen
      modified PTH-R levels. These results suggest that both IGF-1 signaling and PGE2
      formation repress PTH-dependent response in OA osteoblasts, a situation that can
      contribute to abnormal bone remodeling and bone sclerosis in OA.

PMID- 11316000
TI  - Mechanical strain effect on bone-resorbing activity and messenger RNA expressions
      of marker enzymes in isolated osteoclast culture.
AB  - Adaptive modeling and remodeling are controlled by the activities of osteoblasts
      and osteoclasts, which are capable of sensing their mechanical environments and
      regulating deposition or resorption of bone matrix. The effects of mechanical
      stimuli on isolated osteoclasts have been scarcely examined because it has proven
      to be difficult to prepare a number of pure osteoclasts and to cultivate them on
      mineralized substratum during mechanical stimulation. Recently, we developed an
      apparatus for applying mechanical stretching to the ivory slice/plastic plate
      component on which cells could be cultured. The loading frequency, strain rate,
      and generated strain over an ivory surface could be controlled by a personal
      computer. Using this apparatus, we examined the role of mechanical stretching on
      the bone-resorbing activity of the osteoclasts. Mature and highly enriched
      osteoclasts were cultured for 2, 12, and 24 h on the ivory/plate component while
      being subjected to intermittent tensile strain. The stretched osteoclasts showed
      enhanced messenger RNA (mRNA) expression levels of osteoclast marker enzymes,
      tartrate-resistant acid phosphatase (TRAP), and cathepsin K and increases of
      resorbed-pit formation, suggesting that the mechanical stretching up-regulated
      the bone-resorbing activity of the osteoclasts. A stretch-activated cation (SA
      cat) channel blocker significantly inhibited the increases of the mRNA level and
      pit formation after 24 h of stretching. This study suggested the possibility that
      the mature osteoclasts responded to mechanical stretching through a mechanism
      involving a SA-cat channel in the absence of mesenchymal cells and, as a result,
      up-regulated their bone-resorbing activity.

PMID- 11316001
TI  - Mild heat shock induces proliferation, alkaline phosphatase activity, and
      mineralization in human bone marrow stromal cells and Mg-63 cells in vitro.
AB  - Bone formation has been shown to be stimulated by local diathermy in vivo;
      however, the mechanisms involved in this heat-induced osteogenesis are unclear.
      In this study, we investigated the direct effect of temperature on human bone
      marrow-derived stromal cells (BMSCs) and the human osteoblast-like, osteosarcoma
      derived MG-63 cells in culture conditions. Both cell types were shown to tolerate
      the transient exposure to mild heat shock conditions (1 h at 39-41 degrees C),
      and long-term (96 h) exposure at 39 degrees C stimulated DNA synthesis in BMSC
      but caused growth arrest in MG-63 cells. Furthermore, 1-h exposure to higher
      temperatures (42.5-45 degrees C) or continuous 96-h exposure to 40 degrees C or
      41 degrees C inhibited the proliferation of both BMSCs and MG63 cells. The level
      of alkaline phosphatase (ALP) in these cells linearly correlated with the
      increase in temperature, and the ALP expression, either at the basal level or in
      response to 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], was enhanced after a single 1
      h exposure to 42.5 degrees C. In addition, continuous incubation at 39 degrees C
      or repeated transient exposure to 39/41 degrees C greatly enhanced the ability of
      BMSCs to form mineralizing nodules. The heat shock protein HSP70, which was
      expressed constitutively by BMSCs, was found to be up-regulated by hyperthermia
      (39 degrees C) and down-regulated at 33 degrees C. The expression of HSP70 could
      be induced in MG-63 cells by both low- and high-temperature conditions. These
      data suggest that treatment with a mild heat shock induces the proliferation and
      differentiation of osteoprogenitor cells, and the direct effects of temperature
      on bone-forming cells might be one of the mechanisms involved in heat-induced
      bone formation in vivo.

PMID- 11316002
TI  - Glutamate does not play a major role in controlling bone growth.
AB  - Bone cells express glutamate-gated Ca2+-permeable N-methyl-D-aspartate (NMDA)
      receptors and GLAST glutamate transporters. Blocking NMDA receptors has been
      reported to reduce the number of bone resorption pits produced by osteoclasts,
      and mechanical loading alters GLAST transporter expression, which should change
      the extracellular glutamate concentration and NMDA receptor activation. Thus, by
      analogy with the brain, glutamate is postulated to be an important intercellular
      messenger in bone, controlling bone formation and resorption. We found that
      activating or blocking NMDA receptors had no effect on bone formation by rat
      osteoblasts in culture. The number of resorption pits produced by osteoclasts was
      reduced by the NMDA receptor blocker MK-801 but not by another blocker AP-5,
      implying that this effect of MK-801 is unrelated to its glutamate-blocking
      action. By contrast, MK-801, AP-5, and NMDA had no consistent effect on the
      volume of pits. In mice with GLAST glutamate transporters knocked out, no
      differences were detected in mandible and long bone size, morphology,
      trabeculation, regions of muscle attachment, resorption lacunae, or areas of
      formation versus resorption of bone, compared with wild-type siblings. These data
      suggest that glutamate does not play a major role in controlling bone growth.

PMID- 11316003
TI  - Study of the maturation of the organic (type I collagen) and mineral
      (nonstoichiometric apatite) constituents of a calcified tissue (dentin) as a
      function of location: a Fourier transform infrared microspectroscopic
      investigation.
AB  - Fourier transform infrared microspectroscopy (FTIRM) was used to investigate the
      organic and mineral phases of a calcified tissue (dentin) as a function of its
      location from predentin toward enamel. Thin dentin slices (decalcified or not)
      were fixed in formaldehyde and embedded in glycolmethylmethacrylate (GMA).
      Fixation did not denature collagen, and GMA did not interact with organic or
      mineral constituents of dentin. The v1v3 PO4 domain was studied in particular in
      order to estimate mineral maturity and amide I, II, A, and B to obtain data on
      protein conformation. The results showed that dentin apatite became increasingly
      mature (stoichiometric) from the mineralization front toward the enamel,
      especially through loss of HPO4(2-) groups and vacancies. Moreover, collagen
      fibrils became less and less hydrated, suggesting that intrafibrillar
      mineralization partially dehydrated the collagen. Combined study of the organic
      and mineral fractions of calcified tissues may help clarify their relationships
      in physiological and pathological tissues.

PMID- 11316004
TI  - Genetic control of bone density and turnover: role of the collagen 1alpha1,
      estrogen receptor, and vitamin D receptor genes.
AB  - Genetic factors are known to influence both the peak bone mass and probably the
      rate of change in bone density. A range of regulatory and structural genes has
      been proposed to be involved including collagen 1alpha (COL1A1), the estrogen
      receptor (ER), and the vitamin D receptor (VDR), but the actual genes involved
      are uncertain. We therefore studied the role of the COL1A1 and VDR loci in
      control of bone density by linkage in 45 dizygotic twin pairs and 29 nuclear
      families comprising 120 individuals. The influences on bone density of
      polymorphisms of COL1A1, VDR, and ER were studied by association both cross
      sectionally and longitudinally in 193 elderly postmenopausal women (average age,
      69 years) over a mean follow-up time of 6.3 years. Weak linkage of the COL1A1
      locus with bone density was observed in both twins and families (p = 0.02 in both
      data sets), confirming previous observations of linkage of this locus with bone
      density. Association between the MscI polymorphism of COL1A1 and rate of lumbar
      spine bone loss was observed with significant gene-environment interaction
      related to dietary calcium intake (p = 0.0006). In the lowest tertile of dietary
      calcium intake, carriers of "s" alleles lost more bone than "SS" homozygotes (p =
      0.01), whereas the opposite was observed in the highest dietary calcium intake (p
      = 0.003). Association also was observed between rate of bone loss at both the
      femoral neck and the lumbar spine and the TaqI VDR polymorphism (p = 0.03). This
      association was strongest in those in the lowest tertile of calcium intake, also
      suggesting the presence of gene-environment interaction involving dietary calcium
      and VDR, influencing bone turnover. No significant association was observed
      between the PvuII ER polymorphism alone or in combination with VDR or COL1A1
      genotypes, with either bone density or its rate of change. These data support the
      involvement of COL1A1 in determination of bone density and the interaction of
      both COL1A1 and VDR with calcium intake in regulation of change of bone density
      over time.

PMID- 11316005
TI  - Lasofoxifene (CP-336,156) protects against the age-related changes in bone mass,
      bone strength, and total serum cholesterol in intact aged male rats.
AB  - The purpose of this study was to evaluate if long-term (6 months) treatment with
      lasofoxifene (LAS), a new selective estrogen receptor modulator (SERM), can
      protect against age-related changes in bone mass and bone strength in intact aged
      male rats. Sprague-Dawley male rats at 15 months of age were treated (daily oral
      gavage) with either vehicle (n = 12) or LAS at 0.01 mg/kg per day (n = 12) or 0.1
      mg/kg per day (n = 11) for 6 months. A group of 15 rats was necropsied at 15
      months of age and served as basal controls. No significant change was found in
      body weight between basal and vehicle controls. However, an age-related increase
      in fat body mass (+42%) and decrease in lean body mass (-8.5%) was observed in
      controls. Compared with vehicle controls, LAS at both doses significantly
      decreased body weight and fat body mass but did not affect lean body mass. No
      significant difference was found in prostate wet weight among all groups. Total
      serum cholesterol was significantly decreased in all LAS-treated rats compared
      with both the basal and the vehicle controls. Both doses of LAS treatment
      completely prevented the age-related increase in serum osteocalcin. Peripheral
      quantitative computerized tomography (pQCT) analysis at the distal femoral
      metaphysis indicated that the age-related decrease in total density, trabecular
      density, and cortical thickness was completely prevented by treatment with LAS at
      0.01 mg/kg per day or 0.1 mg/kg per day. Histomorphometric analysis of proximal
      tibial cancellous bone showed an age-related decrease in trabecular bone volume
      (TBV; -46%), trabecular number (Tb.N), wall thickness (W.Th), mineral apposition
      rate, and bone formation rate-tissue area referent. Moreover, an age-related
      increase in trabecular separation (Tb.Sp) and eroded surface was observed. LAS at
      0.01 mg/kg per day or 0.1 mg/kg per day completely prevented these age-related
      changes in bone mass, bone structure, and bone turnover. Similarly, the age
      related decrease in TBV and trabecular thickness (Tb.Th) and the age-related
      increase in osteoclast number (Oc.N) and osteoclast surface (Oc.S) in the third
      lumbar vertebral cancellous bone were completely prevented by treatment with LAS
      at both doses. Further, LAS at both doses completely prevented the age-related
      decrease in ultimate strength (-47%) and stiffness (-37%) of the fifth lumbar
      vertebral body. These results show that treatment with LAS for 6 months in male
      rats completely prevents the age-related decreases in bone mass and bone strength
      by inhibiting the increased bone resorption and bone turnover associated with
      aging. Further, LAS reduced total serum cholesterol and did not affect the
      prostate weight in these rats. Our data support the potential use of a SERM for
      protecting against the age-related changes in bone and serum cholesterol in
      elderly men.

PMID- 11316006
TI  - Pubertal maturation characteristics and the rate of bone mass development
      longitudinally toward menarche.
AB  - To assess risks for osteoporosis and to compare bone mass in different groups of
      healthy children or children with diseases, it is important to have knowledge of
      their sexual maturation status during puberty. The aim of our study was to
      evaluate bone mass formation longitudinally in relation to pubertal maturation
      characteristics in healthy white girls. We investigated the bone mineral content
      (BMC) and the bone mineral density (BMD) at different skeletal sites in 151 girls
      with increasing pubertal stages in relation with their chronological age and with
      an early or late onset of puberty or menarche and with a slow or fast maturation.
      Bone mass was measured at the onset of puberty, during puberty, and at menarche.
      We conclude the following: (1) from midpuberty to menarche, the increase in bone
      mass formation is highest at all skeletal sites in white girls; (2) early mature
      girls at the onset of puberty have slightly but definitely lower bone masses at
      all skeletal sites and at all pubertal stages than late mature girls, whereas the
      average bone mass formation from the onset of puberty to menarche is similar in
      both groups; (3) girls with a slow rate of pubertal maturation have lower bone
      mass values 2 years after the onset of puberty, but at menarche bone mass is
      similar compared with fast maturers; and (4) it cannot be confirmed that there is
      an effect of menarcheal age on bone mass values at menarche.

PMID- 11316007
TI  - Inhaled corticosteroids reduce bone mineral density in early postmenopausal but
      not premenopausal asthmatic women.
AB  - Inhaled corticosteroids are widely used in the treatment of bronchial asthma, but
      it is still uncertain whether long-term use of the inhaled corticosteroids
      affects bone metabolism in asthmatic patients. In this study, we examined the
      effect of inhaled beclomethasone dipropionate (BDP) on bone mineral density (BMD)
      and biochemical markers of bone metabolism in pre- and early postmenopausal
      asthmatic women. Thirty-six (17 premenopausal and 19 early postmenopausal)
      asthmatic women and 45 healthy control (24 premenopausal and 21 early
      postmenopausal) women were investigated. All the asthmatic patients were treated
      with BDP (542 +/- 298 microg/day; 100-1200 microg/day) without any systemic
      administration of corticosteroids for at least 1 year. In premenopausal women,
      BMD as well as the biochemical markers of bone metabolism did not differ between
      control subjects and BDP-treated asthmatic patients. By contrast, in early
      postmenopausal women, BMD was significantly lower in BDP-treated asthmatic
      patients than in control subjects. In these early postmenopausal women, serum
      intact osteocalcin concentration was lower in the BDP-treated asthmatic patients
      than in the control subjects whereas urinary free pyridinoline (F-PYD) and free
      deoxypyridinoline (F-DPD) concentrations did not differ between the groups. Thus,
      early postmenopausal, but not premenopausal, asthmatic patients who were treated
      with inhaled BDP had reduced BMD, which was associated with a decreased level of
      the bone formation marker. Ovarian hormones may be protective against the adverse
      effect of inhaled BDP on bone metabolism in the premenopausal patients.

PMID- 11316008
TI  - Naphthol-ASBI phosphate as a preferred substrate for tartrate-resistant acid
      phosphatase isoform 5b.
AB  - Tartrate-resistant acid phosphatase (TRAP) isoform 5b is a potential serum marker
      for osteoclastic activity. Biochemical assays for serum TRAP activity with para
      nitrophenylphosphate (pNPP) have low specificity for bone because of hydrolysis
      by unrelated nontype 5 TRAPs of blood cells and by related isoform 5a. Our
      purpose was to increase the specificity of TRAP assay for osteoclastic activity
      by using naphthol-ASBI phosphate (N-ASBI-P) as a substrate for serum type 5 TRAP
      activity and heparin as an inhibitor of isoform 5a. TRAP activity in individual
      and pooled sera of normal subjects and patients with endstage renal disease
      (ESRD) and rheumatologic diseases was quantitated using pNPP and N-ASBI-P as
      substrate at pH 5.5 and 6.1. For some experiments, heparin (23U/ml) was added as
      a specific inhibitor of isoform 5a activity. Isoforms 5a and 5b were separated
      from serum pools by cation exchange chromatography and identified by
      nondenaturing polyacrylamide gel electrophoresis (PAGE). N-ASBI-P was selectively
      hydrolyzed by TRAP isoform 5b. TRAP assays with pNPP and N-ASBI-P correlated only
      in ESRD sera, which contained primarily isoform 5b. The two assays did not
      correlate in normal or rheumatic sera with significant amounts of 5a. Heparin
      inhibited isoform 5a activity approximately 50% but had little effect on isoform
      5b activity. Biochemical assay of serum TRAP activity can be made specific for
      isoform 5b by using N-ASBI-P and heparin. This method can be adapted to simple
      microplate biochemical or immunochemical assays. This simplified method for
      assessment of osteoclastic TRAP 5b activity warrants a detailed investigation in
      diseases of bone metabolism.

PMID- 11316009
TI  - The use of vitamin K may be a good choice for microgravity-induced bone disorder.

PMID- 11316010
TI  - Evolutionary origins of stigmatization: the functions of social exclusion.
AB  - A reconceptualization of stigma is presented that changes the emphasis from the
      devaluation of an individual's identity to the process by which individuals who
      satisfy certain criteria come to be excluded from various kinds of social
      interactions. The authors propose that phenomena currently placed under the
      general rubric of stigma involve a set of distinct psychological systems designed
      by natural selection to solve specific problems associated with sociality. In
      particular, the authors suggest that human beings possess cognitive adaptations
      designed to cause them to avoid poor social exchange partners, join cooperative
      groups (for purposes of between-group competition and exploitation), and avoid
      contact with those who are differentially likely to carry communicable pathogens.
      The evolutionary view contributes to the current conceptualization of stigma by
      providing an account of the ultimate function of stigmatization and helping to
      explain its consensual nature.

PMID- 11316011
TI  - Developmental origin of the animate-inanimate distinction.
AB  - The authors examine recent theoretical perspectives of the development of the
      animate-inanimate distinction in infancy. From these theoretical views emerge 7
      characteristic properties, each related to physical or psychological causality,
      that distinguish animates from inanimates. The literature is reviewed for
      evidence of infants' ability to perceive and understand each of these properties.
      Infants associate some animate properties with people by 6 months, but they do
      not associate the appropriate properties to the broad category of animates and
      inanimates until at least the middle of the 2nd year. The authors offer a
      theoretical proposal whereby infants acquire knowledge about the properties of
      different object kinds through a sensitive perceptual system and a domain general
      associative learning mechanism that extracts correlations among dynamic and
      static features.

PMID- 11316012
TI  - Just teasing: a conceptual analysis and empirical review.
AB  - Drawing on E. Goffman's concepts of face and strategic interaction, the authors
      define a tease as a playful provocation in which one person comments on something
      relevant to the target. This approach encompasses the diverse behaviors labeled
      teasing, clarifies previous ambiguities, differentiates teasing from related
      practices, and suggests how teasing can lead to hostile or affiliative outcomes.
      The authors then integrate studies of the content of teasing. Studies indicate
      that norm violations and conflict prompt teasing. With development, children
      tease in playful ways, particularly around the ages of 11 and 12 years, and
      understand and enjoy teasing more. Finally, consistent with hypotheses concerning
      contextual variation in face concerns, teasing is more frequent and hostile when
      initiated by high-status and familiar others and men, although gender differences
      are smaller than assumed. The authors conclude by discussing how teasing varies
      according to individual differences and culture.

PMID- 11316013
TI  - Is gratitude a moral affect?
AB  - Gratitude is conceptualized as a moral affect that is analogous to other moral
      emotions such as empathy and guilt. Gratitude has 3 functions that can be
      conceptualized as morally relevant: (a) a moral barometer function (i.e., it is a
      response to the perception that one has been the beneficiary of another person's
      moral actions); (b) a moral motive function (i.e., it motivates the grateful
      person to behave prosocially toward the benefactor and other people); and (c) a
      moral reinforcer function (i.e., when expressed, it encourages benefactors to
      behave morally in the future). The personality and social factors that are
      associated with gratitude are also consistent with a conceptualization of
      gratitude as an affect that is relevant to people's cognitions and behaviors in
      the moral domain.

PMID- 11316014
TI  - Risk as feelings.
AB  - Virtually all current theories of choice under risk or uncertainty are cognitive
      and consequentialist. They assume that people assess the desirability and
      likelihood of possible outcomes of choice alternatives and integrate this
      information through some type of expectation-based calculus to arrive at a
      decision. The authors propose an alternative theoretical perspective, the risk-as
      feelings hypothesis, that highlights the role of affect experienced at the moment
      of decision making. Drawing on research from clinical, physiological, and other
      subfields of psychology, they show that emotional reactions to risky situations
      often diverge from cognitive assessments of those risks. When such divergence
      occurs, emotional reactions often drive behavior. The risk-as-feelings hypothesis
      is shown to explain a wide range of phenomena that have resisted interpretation
      in cognitive-consequentialist terms.

PMID- 11316015
TI  - Laser in situ keratomileusis: three unexpected complications.
AB  - PURPOSE: To report unexpected outcomes in three patients after uneventful laser
      in situ keratomileusis (LASIK) performed using the Nidek EC-5000 excimer laser
      and the Hansatome microkeratome (Bausch & Lomb Surgical). METHODS: LASIK was
      performed with the Nidek EC-5000 excimer laser and the Hansatome microkeratome
      (Bausch & Lomb Surgical) in three patients. RESULTS: In three patients,
      unexpected outcomes were observed. One patient treated for -3.00 D of myopia
      presented with a central island. One patient treated for +2.00 D (+1.00 x 90
      degrees) of hyperopia in both eyes ended up emmetropic in one eye and
      overcorrected in the fellow eye. The third patient with -12.00 D (-2.00 x 180
      degrees) of myopia was treated as -8.60 -1.00 x 180 degrees and at last
      examination was +4.00 D. During these sessions, all other patients treated were
      within +/-0.50 D of emmetropia. CONCLUSION: After LASIK with the Nidek EC-5000
      excimer laser and the Hansatome microkeratome (Bausch & Lomb Surgical),
      unexpected outcomes may still occur, despite controlling all the usual variables.

PMID- 11316016
TI  - Unexpected corneal flattening after laser in situ keratomileusis.
AB  - PURPOSE: To perform a statistical study of the variation (flattening) from the
      surgical radius (sculpted in the corneal stroma) to the final radius of the first
      surface of the cornea after laser in situ keratomileusis (LASIK) for correction
      of myopia. METHODS: The study included 387 eyes with myopia or myopic astigmatism
      that underwent LASIK using the Nidek EC-5000 excimer laser. Mean age was 34 years
      (range, 19 to 75 yr). Mean myopia was -5.19 D (range, 0 to -19.00 D) and mean
      astigmatism was -1.22 D (range, 0 to -5.00 D). The flattening coefficient was
      defined as: (f) = (Rpost-Rs)/Rs where Rpost. was the corneal radius after surgery
      (topography performed 1 month after surgery) and Rs was the surgical radius
      sculpted in the stroma. Mean values and standard deviations of the flattening
      coefficient were calculated for the 387 eyes for four myopic ranges (0 to -3.00
      D, -3.00 to -6.00 D, -6.00 to -9.00 D, and more than -9.00 D), and for three
      astigmatic ranges (0, -0.25 to -2.00 D, and more than -2.00 D). The correlations
      between the flattening coefficient and several preoperative ocular variables were
      obtained. RESULTS: A linear combination of quasi-independent ocular variables
      (age, anterior corneal radius, corneal thickness, sphere and cylinder) was found
      in order to maximize the correlation with the flattening for every range. Values
      for the correlations between 0.4 to 0.5 were obtained. CONCLUSION: The flattening
      phenomenon was characterized by a flattening coefficient (f).

PMID- 11316017
TI  - Prevention of corneal ectasia in laser in situ keratomileusis.
AB  - PURPOSE: Ectasia after laser in situ keratomileusis (LASIK) is a rare but serious
      complication. Prevention includes proper patient selection with detection of
      those at particular risk. Causes of ectasia include predisposition, excessive
      ablation with less than 250 microm of residual stromal bed, thicker than normal
      flap, irregular corneal thickness, and different ablation rates. METHODS: We
      evaluated corneal curvature patterns and their relationship to corneal topography
      and pachymetry maps. RESULTS: Corneal topography (axial, tangential, and
      altimetric) and pachymetry map characteristics of normally astigmatic corneas,
      keratoconus, false-positive and false-negative cases, as well as contact lens
      induced warpage are discussed. CONCLUSIONS: Preoperative pachymetry maps for
      LASIK surgery allow accurate case selection through detection of borderline
      cases, and provide important documentation of preoperative status, as well as
      useful information for improving surgical strategy. Another important parameter
      is the asphericity index.

PMID- 11316018
TI  - Decentration after refractive surgery.
AB  - PURPOSE: To examine factors useful in evaluation of suspect decentration after
      refractive surgery. METHODS: We evaluated 148 cases (eyes) referred to us for
      recentering procedures by review of information obtainable by evaluation of pupil
      position, corneal topography, and corneal curvature gradient. RESULTS: Only a
      minority of eyes (n=5, 3.4%) were truly decentered; in the remaining majority a
      high dioptric gradient with consequent focal scarring was present (n=107, 72.3%).
      In 28 eyes (18.9%), a drifting of the eye during treatment was responsible, and
      in eight eyes (5.4%), a central island was observed. CONCLUSIONS: Proper corneal
      topographical diagnosis reduces the risk of improperly suspecting decentration,
      and for most cases, smoothing of the central cornea is a simple and efficacious
      solution. Recommendations for the prevention of decentration include proper
      patient positioning, special care in treating high myopes, preoperative check of
      pupil displacement nasally, evaluation of preoperative map with detection of high
      temporal curvature gradient, and use of the cross-cylinder technique in the
      treatment of astigmatism.

PMID- 11316019
TI  - Interface fluid and diffuse corneal edema after laser in situ keratomileusis.
AB  - PURPOSE: To report a new complication of interface fluid accumulation and corneal
      edema in an uneventful laser in situ keratomileusis (LASIK) procedure. METHODS:
      Uncomplicated bilateral LASIK for myopia using the Hansatome microkeratome was
      performed. One day postoperatively, the patient noted decreased visual acuity.
      The topical corticosteroid was changed from dexamethasone to prednisolone acetate
      1% every 2 hours. Two weeks later the patient reported worsening visual acuity in
      both eyes. Uncorrected visual acuity was 20/200 in the right eye and 20/100 in
      the left. Slit-lamp biomicroscopy indicated significant fluid build-up in the
      interface. Intraocular pressure (IOP) by Goldmann applanation tonometry was 15
      mmHg in the right eye and 14 mmHg in the left. RESULTS: After 4 weeks,
      intraocular pressure by bidigital pressure was increased and high. The
      corticosteroid was discontinued and antiglaucoma medication lowered the
      intraocular pressure, which resulted in corneal clearing and disappearence of
      interface fluid in both eyes. CONCLUSIONS: Early recognition of this new
      complication of LASIK is necessary. The falsely low reading of IOP in the setting
      of interface fluid was the result of easy compressibility of the fluid-filled
      space and reflects the pressure of the interface fluid. This apparently low IOP
      reading can be an additional sign of the existence of interface fluid. The
      corticosteroid should be discontinued and antiglaucoma medication instituted.
      This should lead to a lowering of intraocular pressure and result in corneal
      clearing and disappearence of the interface fluid with improvement in visual
      acuity.

PMID- 11316020
TI  - Management of corneal epithelial defects following laser in situ keratomileusis.
AB  - PURPOSE: To determine the main principles of postoperative management in patients
      with epithelial defects following LASIK. METHODS: Patients with myopia and myopic
      astigmatism (N=2,972; refraction from -1.25 to -15.50 D) were treated with the
      Nidek EC-5000 excimer laser, using the Chiron Vision HT-230 Hansatome
      microkeratome. We observed 95 cases with intraoperative epithelial damage among
      5,896 operations (1.6%) . Patients received traditional topical medical treatment
      (Tobramycin 0.3%, five times a day; Lacrisifi, six to eight times a day). In eyes
      with an epithelial defect less then 3 mm, no additional medical care was needed.
      In eyes with epithelial defects more then 3 mm, soft therapeutic contact lenses
      were used until total re-epithelialization occurred. RESULTS: Total re
      epithelialization was observed the day following surgery in patients with small
      defects (less then 3 mm). Visual acuity achieved preoperative level 4 to 7 days
      after surgery. Total re-epithelialization in patients with soft contact lenses
      occurred 1 to 3 days after LASIK. On the next day examination, Solcoseryl 20% eye
      gel was added to topical therapy for corneal healing. In these patients visual
      acuity achieved preoperative level 10 to 14 days after surgery. In three eyes
      with large epithelial defects (4 to 5 mm), irregular astigmatism (one eye; 0.02%)
      or against-the-rule astigmatism (two eyes; 0.03%) occurred. Patients complained
      of blurred and double vision. Transepithelial phototherapeutic keratectomy was
      performed after 3 months for epithelial smoothing, with good visual results.
      CONCLUSION: Management of epithelial defects following LASIK can be concentrated
      on avoiding epithelial hyperplasia. Epithelial defects less than 3 mm do not
      appear to produce epithelial hyperplasia. Irregular astigmatism induced by LASIK
      can result in reduced best spectacle-corrected visual acuity. A common cause of
      irregular astigmatism is corneal epithelial remodeling and corneal thickening
      secondary to corneal epithelial defects created at the time of the LASIK
      procedure.

PMID- 11316021
TI  - A retrospective study of laser in situ keratomileusis after radial keratotomy.
AB  - PURPOSE: This is a retrospective study designed to present results of laser in
      situ keratomileusis (LASIK) after radial keratotomy (RK). METHODS: Eighty eyes of
      56 patients underwent LASIK for residual myopia, astigmatism, and hyperopia after
      RK. Absolute mean preoperative spherical equivalent refraction was 2.36 +/- 1.17
      D. Best spectacle-corrected visual acuity (BSCVA) was 20/20 in 56% of eyes, 20/25
      in 25%, 20/30 in 13%, 20/40 in 5%, and 20/60 in 1%. Uncorrected visual acuity was
      better than 20/40 in four eyes. Follow-up ranged from a minimum of 1 day after
      surgery to a maximum of 2 years, with an average of 6 months. RESULTS: Mean final
      absolute spherical equivalent refraction was 0.62 +/- 0.611 D. Six eyes
      experienced a loss of BSCVA of one line, one eye lost two lines, and one lost
      more than two lines. Three eyes had one line of improvement and one eye had two
      lines of improvement. Uncorrected visual acuity was 20/20 in 21 eyes, 20/25 in 20
      eyes, and 20/30 in 19 eyes. There was stromal opacity in two eyes, epithelial
      defects in two eyes, and epithelial ingrowth in four eyes. CONCLUSION: LASIK may
      be an effective treatment for myopia, astigmatism, and hyperopia in patients with
      residual refractive error after RK. Extreme caution should be exercised due to
      the complexity of this group of patients.

PMID- 11316022
TI  - Influence of temperature and humidity on laser in situ keratomileusis outcomes.
AB  - PURPOSE: The influence of ambient factors on the results of refractive surgery is
      not well-known. This study evaluated the influence of temperature and humidity on
      laser in situ keratomileusis (LASIK) outcomes. METHODS: Two hundred thirty-seven
      patients who underwent LASIK at the Clivan Instituto de Oftalmologia in Salvador-
      Bahia--Brazil, between May 1999 and March 2000, were evaluated. A total of 156
      (65.8%) patients were female. Mean age was 30.3 +/- 7.6 years. Refractive errors:
      197 patients (83.12%) had compound myopic astigmatism, 17 patients (7.17%) had
      myopia, 11 patients (4.64%) had compound hyperopic astigmatism, and 12 patients
      (5.07%) had other. Results at 15 and 60 days after LASIK were compared according
      to different levels of temperature and humidity in the operating room during the
      procedure. RESULTS: Patients whose spherical equivalent refraction varied between
      -0.50 to +0.50 D at 15 days after LASIK had surgery performed when the
      temperature was 25.1 +/- 1.4 degrees C and humidity was 45.1 +/- 4.2%; for the
      others, temperature was 24.7 +/- 1.5 degrees C (P = .12) and humidity was 43.0 +/
      4.0% (P = .002). The linear regression coefficient showed that lower temperature
      levels were associated with lower spherical equivalent refractions at 60 days
      after LASIK (r2 = .14; P = .03) but not at 15 days after LASIK (P = .98). The
      evaluation of humidity indicated an influence at 15 days after LASIK (r2 = .44; P
      = .04), as well as at 60 days (r2 = .45; P = .0002). CONCLUSION: Operating room
      environment may influence LASIK outcomes; humidity may be more significant than
      temperature.

PMID- 11316023
TI  - Non-invasive measurement of corneal hydration.
AB  - PURPOSE: To investigate the feasibility of a confocal Raman spectroscopic
      technique for the noncontact assessment of corneal hydration in vivo in two
      legally blind subjects. METHODS: A laser beam (632.8 nm; 15 mJ) was maintained on
      the cornea using a microscope objective lens (25x magnification, NA=0.5, f=10 mm)
      both for focusing the incident light as well as collecting the Raman
      backscattered light, in a 180 degrees backscatter configuration. An optical
      fiber, acting as the confocal pinhole for elimination of light from out-of-focus
      places, was coupled to a spectrometer that dispersed the collected light onto a
      sensitive array-detector for rapid spectral data acquisition over a range from
      2,890 to 3,590 cm(-1). Raman spectra were recorded from the anterior 100 to 150
      microm of the cornea over a period of time before and after topical application
      of a mild dehydrating solution. The ratio between the amplitudes of the signals
      at 3,400 cm(-1) (OH-vibrational mode of water) and 2,940 cm(-1) (CH-vibrational
      mode of proteins) was used as a measure of corneal hydration. RESULTS: High
      signal-to-noise ratio (SNR 25) Raman spectra were obtained from the human corneas
      using 15 mJ of laser light energy. Qualitative changes in the hydration of the
      anterior-most part of the corneas could be observed as a result of the
      dehydrating agent. CONCLUSION: Confocal Raman spectroscopy could potentially be
      applied clinically as a noncontact tool for the assessment of corneal hydration
      in vivo.

PMID- 11316024
TI  - Super vision: dream or reality.
AB  - PURPOSE: To present and evaluate the early clinical experience of laser in situ
      keratomileusis (LASIK) using the custom guided corneal ablation system by NIDEK,
      which includes an OPD-Scan, Final Fit program, and Nidek Multipoint EC-5000
      excimer laser. METHODS: The OPD-Scan diagnostic system containing a scanning slit
      refractometer using skiascopic technology with simultaneous Placido disc corneal
      topography is described. The Final Fit program that converts the refractive error
      and topography data into custom algorithms to couple with the Nidek EC-5000
      Multipoint excimer laser is explained. Thirty-eight cases of LASIK using the
      Nidek MK-2000 microkeratome and the Nidek Multipoint excimer laser with custom
      and conventional treatments are presented. Eyes were divided into two groups:
      LASIK custom group and LASIK conventional group. RESULTS: Predictability and
      attempted correction were similar in both groups. One month after surgery, all
      eyes were between +/-1 line of visual acuity. In the custom LASIK group there was
      a gain of one line in 50% and two lines of visual acuity in 25% of patients at 1
      month after surgery. In the conventional LASIK group there was no gain of lines
      of visual acuity at 1 month. In the comparative group (one eye custom LASIK and
      the other eye conventional LASIK) there was data available for six patients
      (75%). At one month, all patients preferred the vision in their custom LASIK
      treated eye. CONCLUSION: The Nidek LASIK custom and conventional treatments were
      safe and predictable. There was more accuracy, better visual acuity, and more
      subjective satisfaction in the custom LASIK custom treatment group.

PMID- 11316025
TI  - Laser in situ keratomileusis vs. laser epithelial keratomileusis (LASIK vs.
      LASEK).
AB  - PURPOSE: To compare results of laser in situ keratomileusis (LASIK) and laser
      epithelial keratomileusis (LASEK) for the treatment of myopia. METHODS: Two
      groups of fifteen patients (30 eyes) each were assigned to either the LASIK group
      or the LASEK group. LASIK procedure: A Hansatome microkeratome with the ring at
      9.5 mm was used to create the corneal flap (depth, 160 microm). The myopic
      correction was then registered on the Nidek EC-5000 excimer laser and the
      appropriate ablation performed. LASEK procedure: Twenty percent ethyl alcohol was
      placed within the corneal epithelial ring. An intact epithelial flap was
      retracted. The Nidek EC-5000 excimer laser was applied in a similar manner to the
      LASIK procedure. Patients from both groups were followed postoperatively for 6
      months, measuring best spectacle-corrected visual acuity, contrast sensitivity,
      and corneal topographic meridians of 3 mm, 5 mm, and 7 mm. RESULTS: Comparing
      corneal topography, best spectacle-corrected visual acuity, and contrast
      sensitivity data, refractive results in the LASEK group were better than the
      LASIK group. CONCLUSION: Objective data show that with the Nidek EC-5000 excimer
      laser, the LASEK method of corneal splitting may prove superior to the LASIK
      method.

PMID- 11316026
TI  - Clinical results after subepithelial photorefractive keratectomy (LASEK).
AB  - PURPOSE: To study the results of photorefractive keratectomy (PRK) after creation
      of an epithelial flap and replacement of the flap after ablation (LASEK).
      METHODS: PRK was performed with the Nidek EC-5000 excimer laser. The technology
      of subepithelial PRK was developed in experiments in vitro in 10 pig eyes and six
      human eyes. The experiments in vivo were carried out in eight eyes of four
      rabbits. In patients, subepithelial PRK was carried out in 12 eyes with high
      myopia, best spectacle-corrected visual acuity of 20/30 and below. LASIK,
      ordinary PRK, or transepithelial PRK were performed in the second eye to act as a
      control. RESULTS: The basic steps of subepithelial PRK include creation of an
      epithelial flap, refractive ablation, and subsequent repositioning of the
      epithelial flap. In the clinical trial, creation of an epithelial flap was easy
      in five (41.7%) eyes, moderate in four (33.3%) eyes, and difficult in three
      (25.0%) eyes. No pain occurred in six (50%) eyes, some discomfort in four (33.3%)
      eyes, and pain in two (16.7%) eyes. After subepithelial PRK, visual and
      refractive results were similar with both LASIK and PRK. The common components of
      ordinary PRK, transepithelial PRK, and subepithelial PRK are removal of Bowman's
      layer and epithelium. The advantages and disadvantages of subepithelial PRK are
      considered. CONCLUSION: Subepithelial PRK (LASEK) has the potential for
      widespread use in clinical practice, but further development of special
      instruments and techniques would be helpful.

PMID- 11316027
TI  - Effectiveness of laser in situ keratomileusis with the Nidek EC-5000 excimer
      laser for pediatric correction of spherical anisometropia.
AB  - PURPOSE: To determine the effectiveness of laser in situ keratomileusis (LASIK)
      for correction of spherical anisometropia in patients under 18 years of age.
      METHODS: Thirty-eight patients (58 eyes) with myopic spherical anisometropia and
      spherical antimetropia were treated. Group 1 included 31 eyes of 20 children (9
      to 15 yr) and Group 2 included 27 eyes of 18 children under 18 years old (16 to
      17 yr). The difference in refraction between the two eyes in Group 1 was an
      average 5.95 D and in Group 2, 6.92 D. The operations were performed with the
      Nidek EC-5000 eximer laser and the Hansatome Chiron Vision HT-230 microkeratome.
      The procedure was performed under local anesthesia. Patients were followed for 18
      months. Occlusion therapy was started 2 weeks postoperatively and continued for 3
      to 4 months. Ten patients suffered from strabismus; they received orthoptic
      therapy. RESULTS: Uncorrected visual acuity (UCVA) and best spectacle-corrected
      visual acuity (BSCVA) improved after LASIK. The difference in refraction between
      the two eyes was reduced as was the angle of strabismus. Binocular vision
      improved in one patient and simultaneous vision improved in three patients
      (vision in these patients was monocular before treatment). CONCLUSIONS: LASIK
      with the Nidek EC-5000 excimer laser and the Hansatome Chiron Vision HT-230
      microkeratome, together with occlusion and orthoptic therapy for pediatric
      correction of spherical anisometropia, may be an effective procedure that
      facilitates increased visual acuity and improved binocular vision. LASIK appears
      to be a safe surgical procedure for children over 9 years of age.

PMID- 11316028
TI  - Photorefractive keratectomy with customized segmental ablation to correct
      irregular astigmatism after laser in situ keratomileusis.
AB  - PURPOSE: To correct irregular astigmatism after laser in situ keratomileusis
      (LASIK) with customized segmental ablation using the Nidek OPD-Scan (ARK-10000)
      to guide the Nidek EC-5000 excimer laser with the Final Fit software. METHODS:
      One eye of a patient that had undergone LASIK and one enhancement was treated
      using photorefractive keratectomy (PRK) with customized segmental ablation. OPD
      Scan maps were analyzed before and after surgery. The Final Fit software was used
      to link the OPD-Scan to the EC-5000 laser to guide the customized ablation.
      RESULTS: At 1 month postoperatively, best spectacle-corrected visual acuity had
      improved from 20/20-2 to 20/15-2, the patient's subjective evaluation of vision
      was markedly improved, and the postoperative OPD-Scan maps appeared more regular.
      CONCLUSION: Customized segmental ablation can be performed using the Nidek OPD
      Scan and Final Fit software to improve best spectacle-corrected visual acuity and
      minimize irregular astigmatism, which may result from prior surgical procedures.

PMID- 11316029
TI  - Photorefractive keratectomy in Army personnel.

PMID- 11316030
TI  - Intraocular lens implantation and laser in situ keratomileusis (bioptics) to
      correct high myopia and hyperopia with astigmatism.
AB  - PURPOSE: To analyze the refractive outcome of moderate to high myopic and
      hyperopic patients with astigmatism who underwent programmed refractive surgery;
      first lens phacoemulsification with intraocular lens implantation and 3 months
      later, laser in situ keratomileusis (LASIK). METHODS: Four men and eight women
      (22 eyes) with a mean age 47.3 years (range, 38 to 75 yr), and an average
      spherical equivalent refraction of -11.76 D and +5.22 D and (range, -17.50 to
      +8.50 D) underwent two refractive procedures. First, phacoemulsification of the
      lens with a self-sealing incision through clear cornea on the steepest
      topographic axis and implant of a monofocal intraocular lens in the bag was
      performed by two experienced surgeons. Second, LASIK was performed with the Nidek
      EC-5000 excimer laser and the Moria LSK-One microkeratome, by one surgeon. Eyes
      were divided into two different groups. In the first group, the IOL implanted was
      calculated to leave the eye slightly myopic, with final correction to be achieved
      with LASIK. In the second group, the IOL implanted was calculated to achieve
      emmetropia, correcting any residual refractive error with the laser. RESULTS:
      After surgery, mean spherical equivalent refraction was +0.26 D (range, -0.375 to
      +1.50 D). Predictability of refractive outcome: 0 to -1.00 D, 63.63%; +0.25 to
      +1.00 D, 31.80%; +1.25 to +2.00 D, 4.54%. Mean residual refractive astigmatism
      was 0.30 D (range, 0 to 1.50 D). Uncorrected visual acuity of 20/20 or better was
      achieved in 18.3% of eyes; 20/40 or better in 81.8%. No eyes lost two or more
      Snellen lines of visual acuity and no adverse effects were observed. CONCLUSIONS:
      Bioptics (phacoemulsification with IOL implantation followed 3 months later by
      LASIK with the Nidek EC-5000 excimer laser) for correction of moderate to high
      myopia and hyperopia, with astigmatism, enabled us to treat the total refractive
      error and adjust final outcomes.

PMID- 11316031
TI  - Comparative results between standard and bitoric nomograms for astigmatism
      correction.
AB  - PURPOSE: To investigate results of excimer laser correction for mixed
      astigmatism, using two kinds of corneal photoablation; bitoric nomograms for
      cylinder and standard monotoric procedures. METHODS: Intrastromal photoablation
      was performed with the Nidek EC-5000 excimer laser and a lamellar keratotomy was
      created with the Hansatome microkeratome. We selected 46 cases with mixed
      astigmatism. The first group included 28 eyes (average cylinder 4.15 +/- 0.86 D,
      sphere 1.37 +/- 0.18 D). In this group, procedures were performed using bitoric
      nomograms. The second group included 18 eyes (average cylinder 4.05 +/- 0.64 D,
      sphere 1.67 +/- 0.23 D). In this group ablation was performed with monotoric
      nomograms. RESULTS: After 6 months in the bitoric group, average residual
      cylinder was 1.49 +/- 0.24 D, and sphere was -0.57 +/- 0.31 D. In seven cases
      (25%), re-ablations for astigmatism correction were needed. In the monotoric
      group, average postoperative cylinder was 1.89 +/- 0,39 D, and sphere was 0.77 +/
      0.28 D. In eight cases (44%), retreatments were planned. CONCLUSION: Bitoric
      ablations for astigmatic corrections resulted in a decreased frequency of
      reablation as compared to standard monotoric procedures.

PMID- 11316032
TI  - Laser in situ keratomileusis results of DOS and windows software versions for the
      Nidek EC-5000 excimer laser using the same nomogram.
AB  - PURPOSE: To compare the results of laser in situ keratomileusis (LASIK)
      correction for myopia and myopic astigmatism between the previous DOS software
      version and the Windows software version for the Nidek EC-5000 excimer laser,
      using the same nomogram. METHODS: This retrospective review included 2021 eyes
      (980 patients) after LASIK using the Nidek EC-5000 excimer laser. Of these, 1,632
      eyes were corrected with the DOS software version and the other 389 eyes were
      corrected with the Windows software version of the laser. Both groups were
      treated with the same surgical nomogram. Minimum follow-up time was 6 months.
      Patients were classified into range of myopia: low, moderate, and high. RESULTS:
      Postoperative uncorrected visual acuity was not statistically significantly
      different between the two groups in any range of refractive error. There was no
      loss of best spectacle-corrected visual acuity for any patient. Uncorrected
      visual acuity equal to or better than 20/40 was achieved in 96.3% of eyes in the
      Windows version group and 94.9% in the DOS version. CONCLUSION: Results for the
      correction of myopia or myopic astigmatism were similar using the Nidek EC-5000
      excimer laser with either the DOS software version or Windows software version,
      with the same surgical nomogram.

PMID- 11316033
TI  - Comparison of laser in situ keratomileusis outcomes with the Nidek EC-5000 and
      LSX LaserSight excimer lasers.
AB  - PURPOSE: To report the results of laser in situ keratomileusis (LASIK) for myopia
      with and without astigmatism using the Nidek EC-5000 and LaserSight LSX excimer
      laser systems. METHODS: A retrospective analysis of refractive outcomes with each
      laser was conducted. Approximately 2,900 myopic and astigmatic treatments up to 
      10.00 D (spherical equivalent refraction) were analyzed using refractive outcomes
      analysis software. RESULTS: At 6 months postoperatively, 78% of patients treated
      with the Nidek EC-5000 laser and 53% of patients treated with the LaserSight LSX
      laser were within +/-0.50 D of the intended correction. CONCLUSION: A difference
      in safety, stability, and efficacy of LASIK was found that favored the Nidek EC
      5000 excimer laser.

PMID- 11316034
TI  - The Nidek MK-2000 microkeratome system.
AB  - PURPOSE: To assess flap thickness and the performance of the Nidek MK-2000
      microkeratome during laser in situ keratomileusis (LASIK). METHODS: Three hundred
      seventy consecutive eyes of patients undergoing LASIK had the depth of flaps
      measured via subtractive pachymetry. All flaps were created using two different
      model numbers of the Nidek MK-2000 microkeratome. Both 130-microm and 160-microm
      depth plates were evaluated. Microkeratome-induced complications were also
      recorded. RESULTS: Buttonhole flaps and free flaps were not seen in this study.
      One short flap occurred and suction could not be obtained in two eyes. The mean
      flap thickness obtained using the 130-microm depth plate for model number 121 was
      129 +/- 21.8 microm. The mean flap thickness obtained using the 160-microm depth
      plate for model number 121 was 150 +/- 29.6 microm. The mean flap thickness
      obtained using the 130-microm depth plate for model number 65 was 152 +/- 25
      microm. The mean flap thickness obtained using the 160-microm depth plate for
      model number 65 was 173 +/- 26.9 microm. CONCLUSION: The Nidek MK-2000
      microkeratome is safe and creates flaps of predictable thickness.

PMID- 11316035
TI  - Experience with the Nidek MK-2000 microkeratome in 1,220 cases.
AB  - PURPOSE: To evaluate the performance of the Nidek MK-2000 microkeratome. METHODS:
      The Nidek MK-2000 microkeratome was used in 1,220 cases of LASIK with the Nidek
      EC-5000 excimer laser. Patients had a wide range of myopia (-0.75 to -25.00 D),
      hyperopia (+0.75 to +9.00 D) and/or astigmatism (-7.00 to +6.50 D). The flap was
      created with the 130-microm microkeratome plate for 859 eyes, and the 160-microm
      plate for 361 eyes. In 632 eyes, the 8.5-mm ring was used, and the 9.5-mm ring
      was used in 588 eyes. The flap hinge was placed nasally, superiorly, or
      inferiorly depending on the needs of the case. An easy external modification
      allowed us to gently increase and decrease the vacuum level and to perform the
      procedure using a low vacuum regimen, if necessary. RESULTS: The edges of the
      flaps and the corneal surface were of good quality in all eyes. No free flaps
      were noted. One case was aborted because of inappropriate flap formation in a
      patient with a large difference (6.50 D) in corneal curvature in two main
      meridians. This patient successfully underwent LASIK 1 month later, placing the
      flap hinge in the opposite direction. Small epithelial shrinkage was noted in 38
      eyes. No other flap complications were noted. In all patients the flap diameter
      and thickness were close to that estimated by the manufacturer. The vacuum level
      was adequate and stable in all cases. CONCLUSION: The Nidek MK-2000 microkeratome
      was easy to use, predictable, and safe. However, we suggest a modification,
      adding an adjustable head movement to create wider hinge-to-center-of-pupil
      distance and an additional 9.0-mm suction ring.

PMID- 11316036
TI  - Evaluation of the reliability of the Nidek MK-2000 microkeratome for laser in
      situ keratomileusis.
AB  - PURPOSE: To evaluate the performance of the Nidek MK-2000 microkeratome in
      corneal flap creation for laser in situ keratomileusis (LASIK) in Asian eyes and
      the simplicity of its use for the beginner. METHODS: A prospective study of 200
      Asian eyes was performed. The corneal flaps were created using the Nidek MK-2000
      microkeratome 130-microm and 160-microm thickness plates with 8.5- and 9.5-mm
      suction rings. Ease of obtaining suction was evaluated and measurements were done
      for flap thickness, flap diameter, hinge size, and hinge-to-center-of-pupil
      distance. RESULTS: Subjectively, even in small eyes, the procedure of obtaining
      the required suction and creating a good flap was easy and reliable with the
      Nidek MK-2000 microkeratome. Average flap thickness was 120.52 +/- 16.49 microm
      (range, 84 to 162 microm) for the 130-microm thickness plate with the 8.5-mm
      suction ring. Mean flap diameter was 9.16 +/- 0.43 mm, mean hinge size was 4.96
      +/- 0.36 mm, and mean hinge-to-center-of-pupil distance was 4.16 +/- 0.28 mm.
      With the 9.5-mm suction ring, mean flap thickness was 122.06 +/- 18.54 microm
      (range, 84 to 149 microm), mean flap diameter was 9.85 +/- 0.35 mm, mean hinge
      size was 5.28 +/- 0.36 mm, and mean hinge-to-center-of-pupil distance was 4.49 +/
      0.27 mm. For the 160-microm plate with a 8.5-mm suction ring, the flap thickness
      was 172.71 +/- 27.49 microm (range, 121 to 203 microm), flap diameter was 9.13 +
      0.37 mm, mean hinge size was 5.02 +/- 0.29 mm and mean hinge-to-center-of-pupil
      distance was 4.21 +/- 0.29 mm. There were no complications of corneal flap
      creation. CONCLUSION: The Nidek MK-2000 microkeratome was effective, safe, and
      reliable, even in small eyes.

PMID- 11316037
TI  - Prevalence of allergic bronchopulmonary aspergillosis in patients with bronchial
      asthma.
AB  - Two Hundred patients with bronchial asthma were studied to identify the
      prevalence of allergic bronchopulmonary aspergillosis (ABPA). The patients
      selected required intermittent short courses of steroids and their mean duration
      of illness was 12 years. Absolute eosinophil count was > 500/mm3 in 53% of the
      cases. Chest X-rays showed small homogenous shadows with patchy infiltrations in
      25% and fluctuating pneumonic shadows in 14% of the cases. Raised specific IgG
      and positive serum precipitin against Aspergillus fumigatus (AF) were present in
      24% and 13%, respectively. Cases with radiological and immunological suspicion
      were further investigated for ABPA. Skin tests for Type-I and Type-III reactivity
      were positive with AF extract in 87% (n = 47) and 36% (n = 47) of the cases. A
      thorax CT of 31 patients showed central bronchiectasis in 24 cases, labeling
      these patients as ABPA-CB (ABPA with central bronchiectasis) and an other 7 as
      ABPA-S (serological positive). CT was not done in one case who, because of other
      positive findings, was also labeled as ABPA-S. Thus, these 32 asthmatics were
      found to have ABPA. Among them, there was raised specific IgG (100%) and raised
      specifc IgE against AF (100%), positive skin test for Type-I and Type-III
      reactivity (100% and 53%) against AF. There was elevated total IgE (100%, n =
      29), a positive family history of asthma (63%), peripheral eosinophilia (100%)
      and a history of passage of brownish plugs (31%). Radiological findings suggested
      soft shadow with infiltration in 31% and fluctuating pneumonic shadows in 69% of
      cases. CT Thorax (n = 31) showed central bronchiectasis in 78% of theses
      patients. Based on the present data, the prevalence of ABPA in bronchial asthma
      patients is 16% (12% with central bronchiectasis and 4% only serologically
      positive). Therefore, patients should be investigated and diagnosed in an early
      phase of ABPA (ABPA-S) and should be treated to prevent permanent lung damage.

PMID- 11316038
TI  - Survey of the prevalence of asthma, allergic rhinitis and eczema in
      schoolchildren from Khon Kaen, Northeast Thailand. an ISAAC study. International
      Study of Asthma and Allergies in Childhood.
AB  - This survey of schoolchildren from Khon Kaen, Northeast Thailand used the
      standardized ISAAC questionnaires to estimate the prevalence of asthma and other
      allergic diseases and to compare the results with two previous studies. A total
      of 6,068 questionnaires were analyzed (2,658, 45.6% males from the 6 to 7 years
      old group and 3,410, 49.5% male from the 13 to 14 years old group). The three
      predominant cumulative and 12-month conditions discerned from the written
      questionnaires among the 6 to 7 vs 13 to 14 years old were: wheezing, at 18.6%
      and 10.2% vs 20.5% and 11.0%; rhinitis at 38.4% and 33.5% vs 59.4% and 42.5%; and
      eczema at 18.0% and 15.2% vs 9.9% and 7.4%, respectively. The observed
      prevalences in our study were similar to those found in Bangkok and slightly
      higher than those in Chiang Mai, except for 'exercise wheezing' in older children
      which was two times higher in our study than in the two previous studies. Our
      study showed seasonal variation of the 'nose' symptoms. The peak prevalence was
      in the relatively cool and dry season (between November and January), which was
      the same pattern as Chiang Mai but different from Bangkok (which had a perennial
      pattern and less climatic variation). Our results concurred with the two previous
      Thai ISAAC studies. There is a high prevalence of asthma and other allergic
      diseases among Thai children and there has been a four-fold increase in symptoms
      since the last decade. If the trend persists asthma and allergic disease may
      become a pressing health concern of the country.

PMID- 11316039
TI  - Pathogenesis of telangiectasia in scleroderma.
AB  - Scleroderma (progressive systemic sclerosis) is a systemic autoimmune disorder
      characterised by skin sclerosis, calcinosis and changes in microvasculature. The
      etiology of the disease is unknown but both genetic and environmental factors
      have been implicated. Telangiectasia (macroscopically visible dilated skin
      vessels) occurring primarily on the hands and face, are a prominent feature in
      scleroderma and are present in the majority of patients. Similarly,
      telangiectasia are found in patients with hereditary hemorrhagic telangiectasia
      (HHT), a mutational disorder of the germline genes endoglin and ALK-1, members of
      the TGFbeta receptor family, expressed on endothelial cells. Our study
      investigated the number, distribution and microscopic characteristics of
      telangiectasia in both limited (n = 29) and diffuse scleroderma (n = 9) and
      compared findings with 3 patients with HHT. In limited scleroderma, the mean
      number of telangiectasia (hand and face) was 36 (0-150) compared with 23 (0-135)
      in diffuse scieroderma. A significant correlation was observed between the number
      of telangiectasia on the face and on the hands (p = 0.014). The total number of
      telangiectasia correlated significantly with the disease duration (p = 0.009).
      The spatial distribution of the telangiectasia appeared to be random on both
      hands and foreface in contrast with the distribution of subcutaneous
      calcification of the hands which occurred predominantly on the distal and flexor
      surfaces of the first, second and fifth digits. Nailfold microscopic
      capillaroscopy was performed on 12 patients. No significant correlation was
      observed between capillary diameter or density and with total number of
      telangiectasia observed macroscopically. The distribution and microscopic
      appearance of telangiectasia in scleroderma appeared very similar to those
      observed in HHT. In view of these similarities we therefore conclude that
      telangiectactic development in scleroderma may be associated with disorders of
      the TGFb receptor family proteins found on the microvasculature.

PMID- 11316040
TI  - Interleukin-1beta level in gingival crevicular fluid of patients with active
      periodontitis.
AB  - Previous studies revealed that interleukin-1beta (IL-1beta) was detectable in
      gingival crevicular fluid (GCF) of patients with periodontitis, and the level was
      increased in level in gingival tissue extracts of active periodontal disease
      sites (defined as attachment loss > or = 2.5 mm over the preceding 2 months)
      compared to inactive sites or healthy sites. The present study evaluated the
      relationship of IL-1beta level in GCF and periodontal disease status. GCF was
      collected with Periopaper strips from 34 disease-active and 45 disease-inactive
      teeth in 11 untreated periodontitis patients and from 60 teeth in 15 healthy
      control subjects. Disease activity was defined as attachment loss of > or = 2.5
      mm in at least one site of a tooth as determined by sequential probing. The
      absorbed GCF volume was determined using a Periotron 6000 and the crevicular IL
      1beta level was determined using IL-1beta monoclonal antibody (Otsuka
      Pharmaceutical, Japan). IL-1beta was below the detection level of the assay (6
      pg/ml) in the healthy control group but was detected in most teeth of the
      periodontitis group. However, disease-active teeth had higher IL-1beta level
      (Mann-Whitney U-test, p < 0.05) than disease-inactive teeth (mean total IL-1beta
      of 5.89 +/- 7.88 pg/tooth and 1.72 +/- 2.28 pg/tooth; mean concentration of 1.6
      +/- 2.5 ng/ml and 0.6 +/- 0.83 ng/ml, respectively). The level of IL-1beta showed
      no correlation with probing depth, but had significant correlation (p < 0.05)
      with the extent of attachment loss. This study suggests that the level of IL
      1beta in GCF may have a predictive value for determining active and inactive
      periodontal status.

PMID- 11316041
TI  - Nitric oxide production by murine spleen cells stimulated with Porphyromonas
      gingivalis-derived lipopolysaccharide.
AB  - The aim of the present study was to determine whether Porphyromonas gingivalis
      lipopolysaccharide (Pg-LPS) may stimulate nitric oxide (NO) production by murine
      spleen cells. Spleen cells derived from Balb/c mice were cultured in the presence
      of Pg-LPS or LPS from Salmonella Typhosa. The cell were also cultured in the
      presence of Pg-LPS with or without L-arginine, L-arginine plus NG-monomethyl-L
      arginine (NMMA), or IFN-gamma. Furthermore, the plastic non-adherent spleen cells
      were stimulated with Pg-LPS and L-arginine. The results showed that Pg-LPS failed
      to stimulate splenic NO production by themselves. Exogenous L-arginine or IFN
      gamma up-regulated the NO production of Pg-LPS-stimulated spleen cells, but the
      stimulatory effects of L-arginine were completely blocked by NMMA. It was also
      demonstrated that in the presence of Pg-LPS and L-arginine, splenic macrophages
      were the cellular source of NO. These results suggest, therefore, that P.
      gingivalis-LPS may induce murine splenic macrophages to produce NO in a L
      arginine and an IFN-gamma-dependent mechanism.

PMID- 11316042
TI  - High dose chemotherapy and peripheral blood stem cell transplantation for high
      risk primary breast cancer: a single center experience in Thailand.
AB  - Twenty patients with high risk primary breast cancer underwent a high dose
      chemotherapy program at Ramathibodi Hospital, Bangkok. Eligible patients included
      21 women who had a histological diagnosis of breast cancer with more than 10
      axillary lymph nodes involved. The patients first underwent modified radical
      mastectomy, followed by conventional doxorubicin containing adjuvant
      chemotherapy, before entering the treatment program. Peripheral blood stem cells
      were mobilized with cyclophosphamide and G-CSF and were harvested by
      leukapheresis. High dose chemotherapy consisted of cyclophosphamide 5,625 mg/m2,
      cisplatinum 165 mg/m2 and carmustine (BCNU) 600 mg/m2 were subsequently given,
      followed by infusion of the harvested peripheral blood stem cells. The median
      duration of cytopenia after transplantation was 8 days (range 7-12). The median
      expense for the transplantation, in addition to the cost of mastectomy and
      conventional chemotherapy, was 224,396 Baht (approximately US $5,350). Three out
      of the first four patients developed interstitial pneumonitis within three months
      after transplantation. There was one fatal case which was the only regimen
      related mortality. BCNU was then reduced to 450 mg/m2 and lung complications were
      markedly reduced afterwards. The median follow up time was 37 months with a
      median disease free survival of 38 months and overall survival of four years at
      84%.

PMID- 11316043
TI  - Specific IgA antibody to Epstein-Barr viral capsid antigen: a better marker for
      screening nasopharyngeal carcinoma than EBV-DNA detection by polymerase chain
      reaction.
AB  - Nasopharyngeal carcinoma (NPC) is strongly associated with Epstein-Barr virus
      (EBV) infection. To assess whether EBV DNA detection by polymerase chain reaction
      (PCR) or presence of specific serum antibody to viral capsid antigen (VCA) was a
      better marker for screening NPC, nasopharyngeal tissues and blood samples from 58
      NPC patients and 24 non-NPC patients (23 with laryngotracheal stenosis and 1 with
      chronic tonsillitis) were tested for the presence of EBV DNA and serum specific
      VCA antibodies, respectively. EBV DNA was detected in 56 (96.5%) of NPC patients
      and 15 (62.5%) of non-NPC controls, with predominantly EBV type A in both groups.
      On the other hand, specific VCA IgA antibody was detected in the majority of NPC
      patients: 52 (89.7%) while only 4 (16.7%) were detected in non-NPC controls.
      Therefore, specific VCA IgA antibody may serve as a better marker for screening
      NPC than EBV DNA detected by PCR.

PMID- 11316044
TI  - Dengue virus specific T cell responses to live attenuated monovalent dengue-2 and
      tetravalent dengue vaccines.
AB  - The proliferative T cell responses to dengue vaccines were studied using the
      parental strains of dengue vaccines as antigens in 26 dengue immune individuals
      who resided in Bangkok which is the endemic area of dengue infection. The
      magnitude of the T cell responses in subjects with flavivirus cross-reactive
      neutralizing antibody was much higher and the cross-reactivity was broader than
      in those with dengue serotype-specific neutralizing antibodies, Japanese
      encephalitis (JE) specific antibodies or dengue cross-reactive antibodies. The T
      cell response in those with neutralizing antibody against a single serotype or in
      those who had dengue cross-reactive neutralizing antibody was relatively low,
      independent of the level or degree of cross-reactivity of the antibody.
      Evaluation of the proliferative T cell responses in 8 recipients of the
      monovalent dengue-2 (16681-PDK53) or the tetravalent dengue vaccines demonstrated
      that both vaccines induced high levels of neutralizing antibody as well as high
      levels of T cell responses to all serotypes of dengue virus. These results
      indicate that the evaluated dengue vaccines efficiently induced humoral and cell
      mediated immunity comparable to natural infection with dengue virus.

PMID- 11316045
TI  - Clinical associations and prognostic significance of serum anti-p53 antibodies in
      Thai patients with hepatocellular carcinoma.
AB  - Mutations of the p53 gene have been reported to be of prognostic significance in
      hepatocellular carcinoma (HCC). However, the clinical associations and prognostic
      value of anti-p53 antibodies, known to be products of the host immune response to
      these mutations, have been controversial. Serum anti-p53 antibodies were measured
      in 121 Thai patients diagnosed with HCC using a specific enzyme-linked
      immunosorbent assay (ELISA) kit. The clinical/pathological characteristics of the
      patients were compared with respect to the presence of serum anti-p53 antibodies.
      Cox regression analysis was performed to assess factor interaction and
      association with survival. Anti-p53 antibodies were detected in 13.2% (16 of 121)
      of our patients. There were no differences between groups with regard to age,
      sex, viral markers (HBsAg or anti-HCV), severity of liver disease and tumor
      advancement. The median survival rates for patients positive and negative for
      anti-p53 antibodies were 4.0 and 3.0 months, respectively (p = 0.443, by log-rank
      test). Multivariate analysis demonstrated that an advanced Okuda stage, lack of
      therapy and presence of portal vein thrombosis were independent factors related
      to the prognosis of the patients. Nonetheless, the presence of anti-p53
      antibodies did not constitute a predictive variable associated with a poorer
      prognosis. Serum assay of anti-p53 antibodies, although rapid and easily
      performed, may not be suitable as an alternative to molecular detection of
      mutations in assessing tumor advancement and prognosis of patients with HCC.

PMID- 11316046
TI  - HIV-2 infection in Thailand.
AB  - Neither the seroprevalence of HIV-2 nor the sensitivity of enzyme immunoassays
      for the detection of antibodies to this retrovirus have been defined in Thailand.
      We, therefore, Investigated these enigmas using banked sera previously screened
      for HIV-1 by a test that did not distinguish between HIV-1 and HIV-2. All 1,013
      HIV-seroreactive specimens were positive to HIV-1 on retesting, and 740 (73%)
      were reactive to both HIV-1 and HIV-2. The thirty-six samples that reacted with
      HIV-2 at a titer of > or = 1:4,096 were further tested to discriminate between
      HIV-1 and HIV-2 by immunoblot assays incorporating HIV-2 recombinant proteins.
      One specimen was untypeable, but all others were determined to be HIV-1. Seventy
      three percent of sera from Thai HIV-1 infected subjects cross-reacted with HIV-2,
      but not a single case of HIV-2 infection could be confirmed. The finding suggests
      low prevalence of HIV-2 infection in Thailand and that current testing for HIV-2
      antibody is not necessary in Thai population.

PMID- 11316047
TI  - Increasing susceptibility to HAV among members of the young generation in
      Thailand.
AB  - The prevalence of antibodies to hepatitis A virus was studied in 961 children and
      adolescents, randomly selected from five different provinces in Thailand
      (Chonburi, Lopburi, Udonthani, Nakhon Si Thammarat and Lopburi). The highest
      prevalence was found in Nakhon Si Thammarat, with 32.1 percent of those aged 10
      14 years and 57.1 percent of those aged 15-18 years showing evidence of
      protective immunity. However, this high rate could be explained by an outbreak of
      hepatitis A in 1992. In the remaining four provinces, the pattern was typically
      age-related in that all individuals showed between zero and 13 percent antibody
      prevalence until reaching the 15-to-18-year age group where it increased to
      between 5.6 and 22.7 percent. The overall sero-prevalence among all age groups
      was 7.9 percent. Thus, the majority of the younger generation is susceptible to
      hepatitis A virus infection thereby enhancing the impact, should an outbreak
      occur. Preventive measures that might be taken are education aimed at better
      hygiene and sanitation, as well as vaccination of susceptible individuals within
      high-risk populations.

PMID- 11316048
TI  - Maximum-likelihood yes-no procedure for gap detection: effect of track length.
AB  - A maximum-likelihood yes-no procedure was used to measure minimum detectable gaps
      (MDGs) at 1 and 4 kHz using two track lengths (15 and 30 trials). Results from 11
      normal listeners show no difference between MDGs for the two track lengths, and
      variability of the MDGs did not differ significantly for the track lengths.
      Results from simulations indicate that the variability of MDGs from real
      listeners is considerably larger than that imposed by the psychophysical
      procedure. Additional simulations show that random variability of listeners'
      response criterion is a compelling explanation for the excess variability. These
      findings indicate that changes in a listener's threshold over time impose a lower
      bound on the variability obtainable with a yes-no procedure. They imply that
      increasing the number of trials in a track, beyond the minimum number required to
      obtain a stable threshold estimate, offers little or no advantage for the test
      retest reliability of a clinical threshold measurement.

PMID- 11316049
TI  - Preliminary results with the AVR ImpaCt frequency-transposing hearing aid.
AB  - Currently, the only behind-the-ear hearing aid that provides a frequency
      transposition function is the ImpaCt DSR675, recently introduced by AVR
      Communications Ltd. of Israel. In tests with three hearing-impaired adults, the
      performance of the ImpaCt aid(s) was compared with that of each subject's own
      (nontransposing) hearing aids. Recognition of monosyllabic words and medial
      consonants did not differ significantly between the two types of aids. This
      suggests that the transposition function of the ImpaCt was not effective at
      providing these subjects with increased high-frequency speech information, at
      least for the programmable parameters applied in the experiments. However, the
      subjects' understanding of sentences in a competing noise was significantly
      poorer with the ImpaCt than with the subjects' own aids. In that test, the ImpaCt
      aids were programmed to attenuate parts of the noise. The decreased sentence
      recognition may have resulted from this program, which effectively reduced the
      bandwidth of the ImpaCt aids.

PMID- 11316051
TI  - Electrophysiologic correlates of attention versus stimulus competition in young
      male and female listeners.
AB  - The effects of attention and stimulus competition on the late auditory-evoked
      potential (LAEP) were compared in 10 young males and 10 young females. Listeners
      attended to discriminably different oddball tonal sequences presented binaurally
      or monaurally. Peak amplitudes in response to the frequent tones were measured
      for N1, P2, and early and late N2 (N2e and N21) components of the LAEP Whereas N1
      amplitudes increased, the amplitudes of P2 decreased when listeners attended to,
      rather than ignored, the tones. Competition effects for both N1 and P2 resulted
      in reduced amplitudes in the presence of contralateral competition. Although
      findings with N2e and N21 suggested possible attention and competition effects,
      as well as gender differences, the data were inconsistent and will need further
      experimental verification. The present findings with the N1 and P2 components
      provide evidence that different neural processes underlie the attention and
      competition effects in the human brain.

PMID- 11316050
TI  - Development of the Three-Clinic Hearing Aid Selection Profile (HASP).
AB  - The Three-Clinic Hearing Aid Selection Profile (HASP) was developed to assess a
      patient's beliefs about a number of basic considerations felt to be critical to
      the hearing aid selection (HAS) process. These characteristics are felt to be key
      to the acceptance of amplification and include motivation, expectations, cost of
      goods and services, appearance (cosmesis), attitudes about technology, physical
      function/limitations, communication needs, and lifestyle. The results of the
      first investigation suggest that we have been successful in developing a 40-item
      metric with adequate internal consistency reliability that assesses the
      aforementioned characteristics. Second, results of the administration of this
      tool to a large group of individuals indicated that (1) age impacted scores on
      the Technology, Physical Function, and Communicative Needs subscales; (2) gender
      impacted scores on the Motivation, Expectation, Technology, Communicative Needs,
      and Appearance subscales; (3) previous hearing aid use affected scores on the
      Motivation subscale; (4) level of education impacted scores on the Physical
      Function and Lifestyle subscales; and (5) self-perceived hearing handicap had an
      effect on Motivation and Communicative Needs subscale scores. Percentile data
      collected from this subject sample are presented as a benchmark against which to
      evaluate responses from individual patients. Case studies are presented to
      illustrate the potential clinical utility of this device.

PMID- 11316052
TI  - Estimating the location of probe microphones relative to the tympanic membrane.
AB  - This experiment investigated the accuracy with which the location of a probe tip
      relative to the tympanic membrane can be estimated by means of standing waves.
      The ear canal length of each ear of six adult subjects was measured with a probe
      tube using a tactile method. A 6-kHz warble tone was then generated, and the
      position of the standing wave notch in the ear canal was determined using a probe
      microphone by noting the place where the sound pressure level was at a minimum.
      The distance of the notch from the tympanic membrane was then calculated. The
      mean distance of the notch from the tympanic membrane was found to be 14.1 mm. It
      was concluded that this technique is reliable and suitable for clinical use when
      it is important that the probe tube be placed within a known distance of the
      eardrum for accurate measurement of real-ear aided gain.

PMID- 11316053
TI  - Maximum length sequences-auditory brainstem responses from children with auditory
      processing disorders.
AB  - This study was designed to evaluate maximum length sequences-auditory brainstem
      responses (MLS-ABR) in children with auditory processing disorders and to compare
      these results with a normal control group matched for age, intelligence, and
      gender. Although each waveform was analyzed for the presence of waves I, III, and
      V, the primary focus was wave V. Although absolute latency measures for wave V
      were obtained from all subjects, waves I and III were not always identified.
      Although the results showed latency increases for all waveforms in both groups,
      the only significant difference noted was an increase in wave V latency for both
      the left and right ears in the clinical group. These results suggest that the MLS
      ABR may be useful in the assessment of auditory processing disorders.
      Implications for the potential use of the MLS-ABR in management programs are
      discussed.

PMID- 11316054
TI  - Income before outcome?

PMID- 11316055
TI  - Numerous similar tests--a miracle cure in experimental life sciences?

PMID- 11316056
TI  - "Lysine is the Lord", thought some scientists in regard to the group interacting
      with fluorescein isothiocyanate in ATP-binding sites of P-type ATPases but, is it
      not cysteine?
AB  - Isothiocyanates are recognized inhibitors acting on ATP-binding sites of P-type
      ATPases. Detailed studies with modification of proteins in molecules of purified
      ATPases by fluorescein isothiocyanate (FITC) and consequent tryptic hydrolysis
      followed by isolation and sequencing of the respective peptide fragments revealed
      FITC bound to a lysine residue. This residue was then indicated to be essential
      for the interaction of ATP with the P-type ATPases. Nevertheless, upon an
      exchange by site directed mutagenesis of lysine, believed to be essential, the
      expected total inhibition of ATPase activity was missing. In addition, in the
      case of the plasma membrane Ca2+-ATPase, the residual activity still remained
      sensitive to FITC. It was attempted to explain the latter finding by hypothetical
      existence of some other lysine residue essential for the ATPase activity. On the
      contrary, in our previous studies we have shown that, based on the reactivity of
      isothiocyanates, the primary target of FITC in P-type ATPases has to be the SH
      group of a cysteine residue. However, later on, in altered conditions during
      trypsinolysis and sequencing, FITC may become transferred from its original site
      of interaction to a lysine residue and this may lead to final identification of
      the label on a false place. The present study represents all attempt of
      elucidating the controversy whether it is lysine or cysteine that represents the
      FITC-sensitive group truly responsible for the recognition by the active site of
      P-type ATPases of ATP and its binding.

PMID- 11316057
TI  - Calcium store depletion induced by mitochondrial uncoupling in prostatic cells.
AB  - The effects of mitochondrial uncoupling on the calcium homeostasis of prostatic
      cells were investigated using the prostatic cancer cell line LNCaP and indo-1
      spectrofluorimetry. Carbonyl cyanide m-chloro-phenylhydrazone (CCCP) was used as
      uncoupler. Resting LNCaP cells responded to CCCP by a biphasic increase in
      [Ca2+]i. The first phase of increase which corresponded to the release of a
      mitochondrial CCCP-sensitive Ca2+ store was followed by a second increase phase
      consisting of Ca2+ influx through the plasma membrane. The relationship between
      the CCCP- and the InsP3-sensitive stores was investigated using thapsigargin
      (TG). The release part of the Ca2+ response to TG was reduced in a time-dependent
      manner by previous exposure of the cells to CCCP, suggesting that CCCP also acts
      on non-mitochondrial stores. Our results show that CCCP releases Ca2+ from both
      mitochondrial and non-mitochondrial stores in prostatic cells. The possible
      mechanisms of these effects are discussed.

PMID- 11316058
TI  - Determination of partition coefficient by the change of main phase transition.
AB  - The molar partition coefficients of amphiphilic additives, e.g. local
      anesthetics, between the aqueous phase, the liquid crystal and the gel phase of
      lipid membrane can be determined based on a combination of phase transition data
      obtained at high and low concentrations of the lipid in aqueous phase. The data
      obtained at high lipid concentration allow to find the phase diagram lipid
      additive in the aqueous environment. The combination of this diagram with data
      obtained at low lipid and additive concentrations provides direct information on
      the concentration of anesthetics in the lipid and thus allows the calculation of
      the partition coefficient.

PMID- 11316059
TI  - Hormonal modulation of structural alteration of rat ovarian luteinizing/human
      chorionic gonadotropin receptors.
AB  - The structure-stabilizing effect of homologous and heterogeneous desensitization
      and albumin on rat ovarian LH/hCG receptors was analyzed by thermal perturbation
      technique. HCG-induced down-regulation shifted the heat inactivation profile of
      hCG-binding sites to a temperature lower by about 7 degrees C (T50 values). In
      heterogeneous desensitization, which also involves uncoupling of receptors from
      adenylyl cyclase system, only follicle stimulating hormone (FSH) changed the
      stability of ovarian LH/hCG receptors. Stimulation of other hormonal receptors,
      which belong to the family of membrane spanning G protein-linked receptors, i.e.
      beta-adrenergic, glucagon, serotonin and prostaglandin E (PGE) had no effect on
      the stability of the LH/hCG receptor. Reduction of the stability of the LH/hCG
      receptor by about 3 degrees C after PGF2alpha injection to luteinized rats may be
      connected with specific process of luteolysis. On the other hand, albumin had a
      stabilizing effect on the receptor. The receptor destabilizing action of oleic
      acid incorporated into ovarian membranes along with calcium stimulation of
      endogenous phospholipase A (PLA) activity and reversal of these effects when BSA
      was used as fatty acid scavenger, may indicate that free fatty acids are
      responsible for the thermal instability of hCG-binding sites. Fluorescence
      quenching studies indicated that extraction of free fatty acids by albumin
      elevated the accessibility of fluorophores for acrylamide, and suggest that
      modificated lipid-protein interactions may affect the stability of the LH/hCG
      receptor structure.

PMID- 11316060
TI  - Effect of fasting and refeeding on the activities of monoamine oxidase and
      antioxidant enzymes in rat hypothalamus and brown adipose tissue.
AB  - Fasting for 48 h and the same period of recovery induced by 48 h refeeding
      increased rat hypothalamic monoamine oxidase (MAO) activity. However, in the
      interscapular brown adipose tissue (IBAT), only refeeding induced a significant
      elevation of the enzyme activity. As far as hypothalamic antioxidative enzymes
      are concerned, the copper zinc superoxide dismutase (CuZnSOD) activity was
      decreased in refed rats only. However, in the IBAT both food deprivation and
      refeeding induced a significant decrease in catalase (CAT) activity. Under the
      influence of fasting the adrenal glands were strongly activated as judged by the
      increased dopamine-beta-hydroxylase (DBH) activity and decreased cholesterol
      concentration. Refeeding brought both parameters to control levels indicating
      full recovery of these glands. As expected, fasting for 48 h induced a
      significant decrease in serum glucose but an increase in FFA concentrations.
      Thus, it can be concluded that both fasting and refeeding resulted in increased
      activation of hypothalamic MAO, whereas CuZnSOD activity was decreased only by
      refeeding. However, in the IBAT only refeeding increased MAO activity whereas
      both fasting and refeeding decreased that of CAT. In conclusion, it may be
      assumed that food deprivation for 48 h and the same duration of refeeding
      influenced MAO and antioxidative enzymes activities in the rat hypothalamus and
      IBAT in a tissue specific manner.

PMID- 11316061
TI  - Correlation between acute phase-related expression of C/EBPbeta and
      transcriptional regulation of the haptoglobin gene during rat liver development.
AB  - The hepatic 35 kD nucleoprotein participates in transcriptional regulation of the
      haptoglobin gene during the development of rat liver. The same molecular mass and
      trans-acting role of the above protein as the active isoform of C/EBPbeta
      transcription factor, made homology between them possible. We could detect
      C/EBPbeta in control hepatic nuclear extracts not earlier than in the second week
      after the birth. However, the acute-phase reaction induced the expression of 35
      kD-C/EBPbeta at day 7 of postnatal development suggesting that the above trans
      active nucleoprotein displays the structural and functional characteristics of
      C/EBPbeta isoform from that day on.

PMID- 11316062
TI  - Enzymatic digestion of liposome-bound polysaccharides: evidence of bridging
      mechanism.
AB  - Laminarin, a water-soluble polysaccharide is known to induce aggregation and
      fusion of liposomes. Using laminarin specific lysing enzymes for multi-lamellar
      liposomes their aggregation was found to be fully reversible, in contrast to
      small unilamellar liposomes for which irreversible fusion is the main process.
      Moreover, our results indicate that these processes are probably mediated by the
      formation of polysaccharide cross-bridges between adjacent liposomes.

PMID- 11316063
TI  - Rat epididymal fat tissue express all components of the renin-angiotensin system.
AB  - In the present study the gene expression of components of the renin-angiotensin
      system was investigated in fat tissue of rats. mRNAs for angiotensinogen, renin,
      angiotensin-converting enzyme and type I (AT1) angiotensin II receptor were
      detected in the stromal-vascular fraction of the fat tissue and the same mRNAs,
      with the exception of the angiotesin-converting enzyme, in the adipocyte
      fraction. Renin and angiotensin-converting enzyme activity was measured. The main
      source of renin activity was found in adipocytes and some minor activity in the
      stromal-vascular fraction, while the majority of the angiotensin-converting
      enzyme activity was in the stromal-vascular fraction. The present data provide
      evidence for the presence of the active renin-angiotensin system in rat adipose
      tissue.

PMID- 11316064
TI  - Analysis of the CD40/CD40L role in the sustenance of alloreactive antibody
      production.
AB  - CD40 ligand (CD40L) is important for T/B lymphocyte interaction. To understand
      the cellular basis of humoral allosensitization we, therefore: (1) measured CD40L
      protein and gene expression in sensitized and non-sensitized uremic unactivated
      peripheral CD4+ T lymphocytes; (2) studied the impact of blocking the CD40/CD40L
      pathway on alloreactive antibody (allo-Ab) production by engrafted sensitized
      PBLs into severe combined immunodeficient (SCID) mice after in vitro
      preactivation with IL2/LPs/HLA class II allopeptides and adjuvants as a potent
      stimulus to produce allo-Ab (Shoker et al. Transplantation 1999;68;1188); and (3)
      studied the modifying effect of CD40/CD40L blockade on T helper type I and II
      cytokine gene expression in the respective mice spleen. The CD40L protein was
      measured by flow cytometry and the gene expression was measured by quantitative
      RT-PCR. Alloreactive antibodies (alo-Abs) produced by sensitized PBLs engrafted
      into SCID mice with and without blockade of the CD40 receptor were measured by
      the PRA-STAT ELISA method. The modifying effects of CD40 blocking on allo-Ab
      production and cytokine gene expression by the engrafted cells measured by RT-PCR
      were then compared. There was no detectable CD40L protein expression in either
      the uremic or the control groups. The CD40L gene expression of 0.04 +/- 0.02
      attomoles (aM) in the sensitized group was significantly higher than in the non
      sensitized patients (0.009 +/- 0.007 aM, P < 0.0001) or the control CD4+ T cells
      (0.016 +/- 0.004 aM, P < 0.001). Blockade of the CD40 receptor abrogated the
      production of allo-Ab antibodies by the engrafted sensitized cells in 60% of the
      tested mice (n = 10); decreased the mean +/- S.D. optic density of allo-Ab to 0.1
      +/- 0.13 and the mean +/- S.D. PRA to 12 + 16). In the presence of the control
      Ab, allo-Ab production in SCID sera was present in 100% of the 10 SCID mice
      tested; the mean +/- S.D. PRA was 75 +/- 20, and the mean + S.D. OD activity was
      0.412 +/- 0.17. All cytokine genes were, otherwise, expressed in the presence or
      absence of CD40 blockade. The results suggest a potential role of an enhanced
      CD40/CD40L interaction in the sustenance of alloreactive antibody production
      without significant deviation to T helper-like I or II responses. Blocking the
      CD40/CD40L pathway may have a potential therapeutic benefit to treat sensitized
      uremic patients.

PMID- 11316065
TI  - Early lung leukocyte infiltration, HLA and adhesion molecule expression predict
      chronic rejection.
AB  - Obliterative bronchiolitis remains the main cause of graft dysfunction and death
      after 1 year. Defined by an irreversible airway obstruction, bronchiolitis
      obliterans syndrome is usually recognized in the advanced stage of the disease,
      with histological evidence of fibrotic damage. Fibrosis represents the end-stage
      of an inflammatory process, leading to the postulate that chronic lung graft
      dysfunction is preceded by cellular and molecular events. This study was
      performed during the first year following lung transplantation, in the absence of
      histological or functional criteria of chronic rejection. Transbronchial biopsies
      from eight lung allografts were examined. Four developed a bronchiolitis
      obliterans syndrome (Group I), and 4 had good outcomes (Group II) at 2 years.
      Using immunohistochemistry, the aim of the study was to correlate early
      immunological events with graft outcomes at 2 years. An up-regulation of HLA
      class I antigen (P = 0.0001), an overexpression of Ki-67 (P = 0.006) on bronchial
      epithelium, and graft infiltration by CD45+, CD25+ cells (P = 0.003) were
      significantly associated with the development of chronic rejection. An
      overexpression of numerous adhesion molecules was observed. However, only very
      late antigen-4 had a discriminative value (P = 0.04), preceding chronic graft
      dysfunction. Our results suggest that graft dysfunction is associated with early
      molecular and cellular events, and raises the possibility that a
      fibroproliferative disorder is initiated shortly after transplantation. The
      recognition of such early immunological markers might facilitate improved graft
      management and prognosis.

PMID- 11316066
TI  - A study of cytokine gene polymorphisms and protein secretion in renal
      transplantation.
AB  - Although there is evidence that cytokine gene polymorphisms are associated with
      varying quantities of cytokine protein production, the exact role of these
      polymorphisms in allograft rejection remains unclear. In a previous study, we
      demonstrated a significant association between high IL-10 secretion in mixed
      lymphocyte culture (MLC), together with HLA mismatching for at least 4-6
      antigens, with the occurrence of acute rejection following renal transplantation.
      We, therefore, wished to ascertain whether cytokine gene polymorphisms are
      associated with varying levels of protein secretion and/or allograft rejection in
      the same group of patients. Cytokine protein secretion in MLC for IL-4, IL-6, IL
      10 and IFN-gamma was measured by ELISA in 49 patient-donor pairs. Protein
      secretion for the above cytokines was also measured in phytohaemagglutinin (PHA)
      stimulated cultures in 30 normal controls. In both patient and control groups,
      single nucleotide polymorphism analysis for IL-4 G(-590)T, IL-6 G(-174)C, IL-10
      G(-1082)A, IL-10 C(-819)T, IL-10 C(-592)A, TNF-alpha G(-308)A and microsatellite
      analysis for IFNG (CA repeat) was performed. No correlation was found between
      cytokine gene polymorphisms and cytokine protein secretion in either mitogen
      stimulated cultures (control group) or MLC (patient group). In addition, no
      correlation was demonstrated between cytokine gene polymorphisms and renal
      allograft rejection.

PMID- 11316067
TI  - Candesartan cilexetil reduces graft arteriosclerosis in aortic transplantation
      model in rat.
AB  - To date established treatment of transplant arteriosclerosis is basically missing
      and there is a need for new therapeutic approaches. Angiotensin II (Ang II) and
      Ang II receptor type 1 (AT) are present in the vascular wall. Blocking of the AT1
      receptor by pharmacological agents may inhibit damaging effects of Ang II on
      endothelial and smooth muscle cells. The purpose of the study was to evaluate the
      effect of the AT1 receptor blocker Candesartan cilexetil on the development of
      graft arteriosclerosis in a rat aortic transplant model. Two strain combinations
      were used for aortic transplantation: DA to PVG; and PVG to PVG. The animals
      received Candesartan cilexetil treatment (9.5 + 1.4 mg/kg/day) for 8 weeks.
      Candesartan cilexetil treatment reduced neointimal formation both in allografts
      (Qint 30.2 +/- 8.8% vs. 22.1 +/- 8.7%, P < 0.05) and in isografts (Qint 15.5 +/-
      4.4% vs. 6.7 +/- 3.3%, P = 0.0001). Blocking of the AT1 receptor signalling by
      Candesartan cilexetil was also associated with a reduced expression of TGF-beta1.
      Macrophage infiltration was not affected by the treatment. Candesartan cilexetil
      treatment leads to reduced neointimal formation in aortic transplant. The
      positive effect of the drug might be partly explained by a reduction of TGF-beta1
      expression in the grafts. Candesartan treatment may provide another possibility
      for prevention of transplant arteriosclerosis and chronic rejection.

PMID- 11316068
TI  - The proliferative response of p53 knock-out mouse-derived vascular smooth muscle
      cell line, P53LMAC01, to PDGF, when compared with human aortic smooth muscle
      cells.
AB  - To develop an in vitro experimental model of vascular smooth muscle cell
      hyperplasia, a major feature in chronic cardiac rejection, we studied a novel
      vascular smooth muscle cell line, P53LMAC01 (AC01), which was established from
      aortic smooth muscles of p53 knock-out mice, to determine its response to a
      platelet-derived growth factor (PDGF) and to Cyclosporin A (CsA). The responses
      were compared with those of human aortic smooth muscle cells (AOSMC). The AC01
      exhibited a distinct proliferative response to PDGF similar to that of AOSMC
      under serum-free conditions. 10 ng/ml of PDGF-BB increased by a factor of 4.5 and
      PDGF-AB doubled the thymidine uptake, but PDGF-AA caused only a slight increase.
      The proliferation was markedly inhibited by 10(-6) M of CsA but less affected by
      10(-7) M. These results indicate that the AC01 cell line could provide a
      convenient experimental system for investigating chronic rejection in vitro and
      that the system might work as a screening model of agents for treating transplant
      related arteriosclerosis.

PMID- 11316069
TI  - Influence of patient and donor cytokine genotypes on renal allograft rejection:
      evidence from a single centre study.
AB  - Cytokines are key immune mediators and it has been suggested that cytokine gene
      polymorphisms affecting expression influence rejection or tolerance. This study
      sought to examine this hypothesis with the aim of identifying predictive genotype
      markers for rejection. The study group consisted of 120 consecutive first
      cadaveric recipient-donor pairs transplanted at a single centre, between 1994 and
      1997. PCR utilising sequence-specific primers (SSP) methodology was optimised for
      genotyping recipient and donor DNA for the following polymorphisms: tumour
      necrosis factor (TNF) -alpha (-308, G/A), interleukin (IL)-10 (-1082, G/A), IL-4
      (-590, C/T), transforming growth factor (TGF) -beta1 (+915, G/C). Recipient-donor
      pairs were divided into rejectors (n = 28) and non-rejectors (n = 92). Each group
      was further stratified according to number of rejection episodes and HLA-DR
      mismatching. Recipient-donor pairs both lacking the IL-4*T allele (recipient low
      producer/donor low producer) were significantly increased in the rejector group
      (P = 0.02). Also, the combination of recipient IL-10*A negative/donor IL-10*A
      positive (recipient high producer/donor low producer), was significantly
      decreased in multiple rejectors (P = 0.04). No significant associations were
      detected between TNF-alpha and TGF-beta1, and rejection. This study suggests that
      the combination of recipient-donor IL-4 and IL-10 genotypes may be important in
      renal transplantation outcome. The results appear to corroborate the protective
      role of both of these cytokines, possibly due to their ability to suppress
      inflammation. However, due to conflicting results from this and other studies, a
      multi-centre collaborative study may be required to determine whether cytokine
      genotypes are significant, independent predictors of renal allograft rejection.

PMID- 11316070
TI  - Combined FTY720/cyclosporine A treatment promotes graft survival and lowers the
      peripheral lymphocyte count in DA to lewis heart and skin transplantation models.
AB  - OBJECTIVE: The immunomodulator, FTY720, lowers the peripheral lymphocyte count
      (PLC) by inducing migration of circulating lymphocytes to secondary lymphoid
      organs. We investigated the efficacy of mono- vs. combined-FTY720/CsA therapy on
      graft survival (GS) and on lowering the PLC in a solid organ and a skin graft
      model, using strains with strong MHC disparity. METHODS: Heterotopic cardiac or
      tail skin grafting was performed using the DA (RT1a) to Lewis (RT1(1)) rat strain
      combination. FTY720 was administered as a single daily dose by gavage alone or in
      combination with subcutaneously delivered CsA. PLC, body weight and drug
      concentrations were determined on day 7, 28, or the day of rejection. MAIN
      FINDINGS: In placebo-treated animals the heart and skin allografts rejected after
      6 and 8 days. FTY720 delayed rejection of both the solid organ and skin grafts.
      The maximal effect was achieved at 1 mg x kg(-l) x day(-1) FTY720, resulting in a
      median survival time (MST) of 14 days for both allotransplants comparable to the
      effect achieved by 1 mg x kg x day(-1) CsA in both models. In the cardiac graft
      experiment with CsA co-administration, doses of 0.3 and 1 mg/kg were used. Under
      these conditions very small doses of FTY720 were effective in maintaining grafts
      throughout the treatment period. Adding higher FTY720 doses to the 1 mg x kg(-1)
      x day(-1) CsA was needed to effectively extend the skin GS, e.g. 0.3 mg x kg(-l)
      x day(-1) FTY720 prolonged GS from 13 to 47.5 days MST, i.e. well beyond the 28
      day-treatment period. CsA did not influence the PLC at clinically relevant doses.
      FTY720 lowered the PLC significantly and dose-dependently, at doses lower than
      those needed for the prolongation of both cardiac and skin GS with FTY720
      monotherapy. In rats with skin grafts the PLC was markedly lowered up to 1 mg x
      kg(-1) x day(-1) FTY720, whereas, in the heart model, it was lowered up to 0.1 mg
      x kg(-1) x day(-1). Independently of the graft type, within the combination
      regimens 0.3 mg x kg(-1) x day(-1) FTY720 achieved a maximal PLC depletion.
      CONCLUSIONS: Combining FTY720 and CsA was very well tolerated with respect to
      weight gain and lack of any clinically detectable infections. In the strain
      combination used FTY720 monotherapy was less effective than previously reported
      in maintaining grafts. The two-drug regimens extended strikingly the GS for both
      models. However, the prolongation of the heart GS was smoothly dose-related with
      FTY720 doses ranging from 0.01 to 1 mg x kg(-1) x day(-1) , whereas, the skin
      graft prolongation was modest at doses up to 0.1 mg x kg(-1) x day(-1) and
      remarkably enhanced at 0.3 and 1 mg x kg(-1) x day(-1) FTY720.

PMID- 11316071
TI  - Analysis of alloreactivity and intragraft cytokine profiles in living donor liver
      transplant recipients with graft acceptance.
AB  - Although some previous studies have indicated the possibility of
      immunosuppression withdrawal in clinical liver transplantation, the mechanism of
      graft acceptance is not clear. The aim of this study is to elucidate the
      alloreactivity against the donor and intragraft cytokine profiles in living donor
      liver transplant (LDLT) recipients with graft acceptance. In October 1999, we had
      23 patients who survived without immunosuppression after LDLT with a median drug
      free period of 25 months (range: 3-69 months). They consisted of six patients who
      were electively weaned by an elective weaning protocol and 17 either forcibly or
      accidentally weaned patients due to various causes but mainly due to infection.
      We evaluated the alloreactivity against the donor in these patients by a mixed
      lymphocyte reaction and intragraft cytokine profiles by real-time reverse
      transcriptase-polymerase chain reaction. The development of donor-specific
      hyporeactivity was observed in the patients with graft acceptance. The cytokine
      pattern in the supernatant of the culture medium revealed a down regulation of T
      helper (Th) 1 cytokine INF gamma against the donor while no significant
      difference was seen in Th2 cytokine IL-10. Regarding the intragraft cytokine
      profiles, we could find no amplification of Thl cytokines (IL-2, INF y) and IL-4
      while some of the patients revealed a gene expression of IL-10 with no
      significant difference from that of the normal, untransplanted liver specimen. In
      addition, no difference was observed in any other cytokines (IL-1beta, IL-8, IL
      15, TNFalpha) compared with those of the normal controls. We propose that the
      down regulation of Th1 cytokine is one possible mechanism of graft acceptance in
      LDLT recipients.

PMID- 11316072
TI  - Thermo water alpha monitor.

PMID- 11316073
TI  - Radio frequency radiation exposure standards: considerations for harmonization.
AB  - Radio frequency radiation exposure standards vary in origin, development process,
      legal status, and in the actual exposure limits. To identify the sources of
      differences in limits, we evaluated technical aspects of eight standards that
      included supporting information on the scientific data and rationale. Comparisons
      were made among the standards by examining the scope of the underlying database,
      the rationales for safety factors and other issues underlying exposure limits in
      the energy-deposition range (0.1 MHz to 10.0 GHz) and in the surface-heating
      range (about 10 or 15 GHz to 300 GHz). The framework for this assessment was
      based on the methods recommended by the scientific and regulatory organizations
      for developing health-based exposure limits. General guidelines for performing
      risk assessments for threshold acting agents have been developed by the U.S.
      Environmental Protection Agency, Health Canada's Environmental Health
      Directorate, and the International Program on Chemical Safety of the World Health
      Organization. This general methodology was applied to radiofrequency radiation
      for this assessment. Because these methods strive to identify scientific issues
      and separate them from risk management or policy, they provide a basis for
      evaluation of standards in this paper. This distinction can provide a foundation
      for the longer-term goal of global harmonization of radio frequency radiation
      standards. Each of the standards evaluated in the energy-deposition range was
      found to use the same basic restriction, based on biological data and a 10-fold
      safety factor, yet explanations reflect different interpretations of the
      underlying biological data. Rationales differ for the magnitude of the safety
      factor, for the circumstances of exposure, for the nature of sensitive
      populations, and for the presumed health status of the individuals for whom the
      basic restriction is applicable. In the surface-heating range, broad variability
      in exposure limits are seen in the limit itself, as well as in the approach to
      time averaging and frequency dependence. Averaging times differ among standards,
      as do tissue geometries for defining partial-body exposures. The differences in
      approaches to develop the standards do not completely explain differences among
      the exposure limits, and methods for computing exposure limits from basic
      restrictions are not always defined. This analysis suggests harmonization of
      standards will require more detailed review and coordination of biological and
      engineering data and of policy options.

PMID- 11316074
TI  - Radiological impact in Greece of the Chernobyl accident--a 10-y retrospective
      synopsis.
AB  - The present study summarizes the published results of the studies of the
      Environmental Radioactivity Laboratory on the radiological impact in Greece of
      the Chernobyl nuclear accident. Some unpublished data from personal
      communications also have been used to present the time evolution of the studies.
      The radiological impact in Greece of the Chernobyl accident is examined in two
      separate phases: that of the acute effects and that of the delayed effects. Some
      measurements cover the whole period from the accidental pollution to the return
      to pre-accident levels and are used for estimations of ecological half-lives. The
      composition of radioactive fallout is examined, and the integrated concentrations
      of the principal radionuclides in the fallout are presented. The variations in
      the air concentrations of certain radionuclides and those of the gamma-ray
      intensity are presented as well. Some results from the study of hot particles
      detected during the acute phase are also given. The radioactive contamination of
      abiotic environmental components, food, and crops during the acute and the
      delayed effects phases are discussed in relation to the radiological impact on
      the population.

PMID- 11316075
TI  - Risks of fatal cancer from inhalation of 239,240plutonium by humans: a combined
      four-method approach with uncertainty evaluation.
AB  - The risk per unit dose to the four primary cancer sites for plutonium inhalation
      exposure (lung, liver, bone, bone marrow) is estimated by combining the risk
      estimates that are derived from four independent approaches. Each approach
      represents a fundamentally different source of data from which plutonium risk
      estimates can be derived. These are: (1) epidemiologic studies of workers exposed
      to plutonium; (2) epidemiologic studies of persons exposed to low-LET radiation
      combined with a factor for the relative biological effectiveness (RBE) of
      plutonium alpha particles appropriate for each cancer site of concern; (3)
      epidemiologic studies of persons exposed to alpha-emitting radionuclides other
      than plutonium; and (4) controlled studies of animals exposed to plutonium and
      other alpha-emitting radionuclides extrapolated to humans. This procedure yielded
      the following organ-specific estimates of the distribution of mortality risk per
      unit dose from exposure to plutonium expressed as the median estimate with the
      5th to 95th percentiles of the distribution in parentheses: lung 0.13 Gy(-1)
      (0.022-0.53 Gy(-1)); liver 0.057 Gy(-1) (0.011-0.47 Gy(-1)); bone 0.0013 Gy(-1)
      (0.000060-0.025 Gy(-1)); bone marrow (leukemia), 0.013 Gy(-1) (0.00061-0.05 Gy(
      1)). Because the different tissues do not receive the same dose following an
      inhalation exposure, the mortality risk per unit intake of activity via
      inhalation of a 1-microm AMAD plutonium aerosol also was determined. To do this,
      inhalation dose coefficients based on the most recent ICRP models and accounting
      for input parameter uncertainties were combined with the risk coefficients
      described above. The following estimates of the distribution of mortality risk
      per unit intake were determined for a 1-microm AMAD plutonium aerosol with a
      geometric standard deviation of 2.5: lung 5.3 x 10(-7) Bq(-1) (0.65-35 x 10(-7)
      Bq(-1)), liver 1.2 x 10(-7) Bq(-1) (0.091-20 x 10(-7) Bq(-1)), bone 0.11 x 10(-7)
      Bq(-1) (0.0030-4.3 x 10(-7) Bq(-1)), bone marrow (leukemia) 0.049 x 10(-7) Bq(-1)
      (0.0017-0.59 x 10(-7) Bq(-1)). The cancer mortality risk for all sites was
      estimated to be 10 x 10(-7) Bq(-1) (2.1-55 x 10(-7) Bq(-1))--a result that agrees
      very well with other recent estimates. The large uncertainties in the risks per
      unit intake of activity reflect the combined uncertainty in the dose and risk
      coefficients.

PMID- 11316076
TI  - Assessing excess lifetime risk for disease after radiation exposure.
AB  - In this paper, we define the excess lifetime risk for a disease due to radiation
      exposure, and we evaluate the excess lifetime risk for an exposed group with the
      same age and with a mixture of ages. We propose two methods to estimate the
      excess lifetime risk: the standard maximum likelihood approach and a Monte-Carlo
      approach. Both approaches allow us to construct confidence intervals for the
      excess lifetime risk and perform hypothesis testing to compare two excess risks.
      The maximum likelihood approach is straightforward and computationally simple;
      however, it may not provide good approximations when the normality assumption is
      violated. The Monte-Carlo approach is always reliable, but often involves heavier
      computations and additional programming. These two approaches are illustrated and
      discussed based on a pooled analysis of five cohorts exposed to external
      radiation and followed up for subsequent thyroid cancer incidence.

PMID- 11316077
TI  - Radium-226, 232Th, and 40K distribution in the environment of Kaiga of south west
      coast of India.
AB  - Systematic studies on gamma radiation level and the distribution of natural
      radionuclides were carried out under a pre-operational survey for the
      establishment of baseline data on background radiation level and the distribution
      of radio-nuclides in the environment of Kaiga, in the south west coast of India,
      where a nuclear power reactor of 235 MWe has just been commissioned. The external
      gamma absorbed dose rates prevailing in the region were measured using a portable
      plastic scintillometer. Soil samples from 18 stations were collected from depth
      intervals of 0-5, 5-10, and 10-25 cm and analyzed for their 226Ra, 232Th, and 40K
      activity concentrations by gamma spectrometry employing a 90 cc PGT HpGe detector
      coupled to an EG&G ORTEC 8K multichannel analyzer. The activity of 226Ra was
      found to vary between 15.5-61.2 Bq kg(-1) with a mean value of 31.3 Bq kg(-1),
      that of 232Th varies between 11.4-41.9 Bq kg(-1) with a mean value of 27.5 Bq kg(
      1) and of 40K between 78.3-254.8 Bq kg(-1) with a mean value of 159.9 Bq kg(-1)
      in 0-5 cm soil profiles of the region. The contributions of 238U, 232Th, and 40K
      to the total gamma absorbed dose rate were 39.9%, 40.7%, and 16.0%, respectively.
      The gamma absorbed dose rate in air estimated using the results of activity
      concentration of 226Ra, 232Th, and 40K are found to compare well with that of the
      direct measurement. The results of the study were compared with the literature
      values reported for other environs of the country as well as the world, and
      conclusions are drawn.

PMID- 11316078
TI  - Impact on internal doses of photon SAFs derived with the GSF adult male voxel
      phantom.
AB  - This paper describes the effect on over 3,000 sets of internal dose estimates of
      using photon Specific Absorbed Fractions (SAFs) calculated using two different
      types of phantoms, specifically the MIRD-type anthropomorphic phantom originally
      developed by Snyder and the new adult male voxel phantom, GOLEM, developed at
      GSF. The SAFs based on the MIRD-type phantom are currently used by the
      International Commission on Radiological Protection (ICRP) in internal dose
      calculations, but there are suggestions of moving towards SAFs generated from
      voxel phantoms, thus there is an interest in the potential differences in
      internal doses. Overall, it is found that some tissue doses calculated using the
      voxel phantoms can differ significantly from those of the MIRD-type phantom;
      however, the effective dose appears to be quite robust to changes in photon SAFs.

PMID- 11316079
TI  - Drinking water standards for radionuclides: the dilemma and a possible
      resolution.
AB  - The U.S. Environmental Protection Agency (EPA) is undertaking a revision of
      existing standards for radionuclides in drinking water. The Safe Drinking Water
      Act specifies that any revision "shall maintain or provide for greater protection
      of the health of persons." This provision appears to require that existing
      standards (maximum contaminant levels, MCLs) cannot be relaxed. Such a
      requirement presents a dilemma for two reasons. First, EPA has shown that the MCL
      for radium was not cost-effective. Second, MCLs for beta/gamma-emitting
      radionuclides incorporate outdated approaches to estimating dose from ingestion
      of radionuclides and, thus, appear to violate provisions of the Safe Drinking
      Water Act concerning the use of sound science in setting standards. We suggest
      that this dilemma can be resolved based on an argument that the standard for
      protection of public health mandated by the Safe Drinking Water Act is one of
      applying best-available technology for removal of contaminants from drinking
      water at a reasonable cost, not one of meeting previously established MCLs.

PMID- 11316080
TI  - Impact of comparison group on cohort dose response regression: an example using
      risk estimation in atomic-bomb survivors.
AB  - Cohort-based dose-response analyses can be biased if based on a comparison group
      that is not comparable to the exposed persons with respect to uncontrolled
      factors related to disease incidence or mortality. When data exist over a range
      of doses including the very low dose region, internal regression standardized
      analyses based on the regression intercept derived from the exposed subcohort
      alone can provide risk estimates that are not subject to such comparison-group
      bias. In the Life Span Study cohort of atomic-bomb survivors, persons with dose
      estimates of zero comprise a broader geographic distribution than that of persons
      with non-zero dose estimates. Because there is geographic variation in mortality
      rates, the zero-dose persons might bias background rate estimates thereby
      affecting inference about radiation risk. This is illustrated using mortality due
      to all causes. Restricting the comparison group to certain geographically defined
      subcohorts resulted in as much as a 6% increase or 8% decrease in the risk
      estimate. This bias can be corrected using an SMR-type estimate in the regression
      model, allowing retention of the comparison group in the analysis if it is needed
      for stability or precision in estimating age, time, and sex effects.
      Consideration of heterogeneity in comparison groups is particularly important in
      dose-response studies focused on low doses at which the response may be
      comparable in magnitude to such heterogeneity.

PMID- 11316081
TI  - Comparison of angular free-in-air and tissue-equivalent phantom response
      measurements in p-MOSFET dosimeters.
AB  - Metal Oxide Semiconductor Field Effect Transistor (MOSFET) radiation dosimeters
      have found recent application in providing real-time measurement in diagnostic
      radiology as well as in radiotherapy. Due to the design of the MOSFET dosimeter,
      the response is dependent on both energy and angulation with respect to the
      direction of primary radiation. The axial angular dependence has been
      characterized for both free-in-air and for tissue-equivalent phantoms. However,
      neither the angular dependence normal (90-degree) to the axial rotation, nor the
      effects of various tissue compositions on angular dependence, have been
      investigated for radiation energies in the diagnostic range. To characterize the
      angular dependence normal to the axial rotation, we exposed three "high
      sensitivity" MOSFET dosimeters simultaneously to x-rays from a medical diagnostic
      x-ray unit over a 360-degree rotation, at 22.5-degree increments, for both free
      in-air and in lung, skeletal, and soft tissue-equivalent phantoms. The MOSFET
      dosimeters clearly showed an angular dependence in the orientation normal-to
      axial as well as in the axial rotation, both for free-in-air and in tissue
      equivalent phantoms. Significant variations in response occurred when the MOSFETs
      were exposed at incident angles between 90 degrees and 180 degrees normal-to
      axial, as compared to the normal position (i.e., the zero-degree position with
      the bubble-side of the MOSFETs facing the radiation source). A maximum decrease
      in response to 32% of normal was observed when the distal ends (end opposite the
      wire lead) of the dosimeters were pointing directly away from the x-ray source
      (270-degree position). To avoid significant errors in MOSFET dosimeter readings,
      placement of the dosimeters should be consistent, and care should be taken to
      avoid orienting the dosimeter with its sensitive region (bubble side) facing away
      from the source of primary radiation at particular angles.

PMID- 11316082
TI  - A unique find (an interesting story as told to Ken Miller by Ed Landa).

PMID- 11316083
TI  - A simple method for assessing exposure to internal emitters.
AB  - One of the most challenging aspects of regulatory compliance can be demonstrating
      compliance with internal dosimetry requirements. For long-lived alpha-emitting
      radionuclides in particular, the sensitivity and accuracy of bioassay analysis
      and whole body counting may not allow for adequate assessment of intakes. Simple
      and effective measures can be used to control the workplace for the internal
      hazards associated with long-lived radioactive material using methods that
      measure directly the air to which workers are exposed. This paper provides an
      easy assessment tool that uses direct measurement of the specific activity of
      dusts in breathing zone air to evaluate internal exposures. Using this method,
      sensitive assessments can be made to determine if intakes are likely to have
      occurred and, if so, at what magnitude. It is not a substitute for confirmatory
      bioassay or whole body counting but a simple method to evaluate expectations for
      internal exposures.

PMID- 11316084
TI  - Radon measurements and analysis for central Pennsylvania counties having elevated
      radon levels.
AB  - The U.S. EPA identified South Central Pennsylvania as a region having elevated
      radon levels. The thnist of this paper is to examine in some detail the TCS
      Industries, Inc., data base for eight Central Pennsylvania counties having a
      combined population of about 1.7 million people, which is 14% of the state
      population. TCS has been making and analyzing radon measurements since 1986.
      During the period 1986 to 1999 more than 125,000 measurements were recorded in
      the TCS data base. The data consisted of analyzed results from four subsets.
      Results were from mail order charcoal canisters, bulk orders from RMP certified
      companies for their placement, wholesales to retail vendors, and also direct home
      placement of canisters, track detectors, and continuous radon monitors. The data
      base for the eight South Central Pennsylvania counties for tile 13-y period
      consists of more than 27,000 screening measurements from non-duplicated
      addresses. The results were assembled into three studies. The locations of tile
      measurements were converted into individual latitude and longitude values. The
      data were divided into four blocks of concentrations from 740 Bq m(-3) to over
      4,440 Bq m(-3). The data were plotted on computer generated maps for South
      Central Pennsylvania. The plots indicated both hot spots and regions of
      relatively uniform chronic levels of 740 to 1,480 Bq m(-3). An average value of
      the basement to first floor concentrations ratio was constructed from
      measurements made by TCS for real estate purposes. The ratio represents 1,608
      sets of simultaneous measurements of basements and first floor radon values above
      37 Bq m(-3). The measurements were made by trained personnel performed under tile
      EPA protocol for closed house conditions. The ratio was 2.3 at 1 standard
      deviation of 0.05 of the mean. A third study assembled all of the data into first
      floor radon concentrations and separately for addresses with only basement
      values. The average concentration data within each of the eight counties were
      converted into the probability of fatal lung cancers and compared with
      occupational risk of fatal cancers for nuclear power plant workers. This study
      illustrates the importance of a continuing strong measurement program in South
      Central Pennsylvania.

PMID- 11316085
TI  - Some experiences with treating thyroid cancer patients.
AB  - U.S. NRC Regulatory Guide 8.39 provides for the release of patients treated with
      131I provided that predetermined calculations indicate that no member of the
      public will receive a total dose equivalent in excess of 5 mSv (500 mrem). When
      this condition cannot be met or there are other reasons for keeping the patient
      hospitalized after treatment, control of contamination and exposure from the
      patient must be taken into consideration. If the patients are hospitalized
      following treatment, decontaminating the patient's room after discharge and
      controlling the exposure potential from the patient are considerations for the
      hospital radiation safety staff. This paper reviews the experiences from fifty
      patients treated as inpatients over the past two years.

PMID- 11316086
TI  - Inspection of lead aprons: criteria for rejection.
AB  - Lead aprons utilized by personnel performing fluoroscopy are routinely inspected
      for damage to comply with the requirements of hospital accrediting organizations.
      Fluoroscopic or radiographic examination of lead aprons may reveal imperfections
      ranging from small pinholes to large tears. Currently, there are no standards
      establishing a criteria for acceptance or rejection of lead aprons. As a
      consequence, many facilities have established arbitrary rejection criteria. Often
      lead aprons are discarded due to small imperfections, a practice that can become
      costly to these institutions. We have calculated increases in doses to the whole
      body for varying sizes of holes, including special consideration of the effects
      on effective dose equivalent when the hole is over the testes and thyroid. ALARA
      standards for cost per personsievert averted are used to establish a rational
      basis for criteria of acceptance or rejection of lead aprons.

PMID- 11316087
TI  - Protection of research subjects with emphasis on protocols involving radiation.
AB  - Approval by an institutional review board (IRB) or human studies committee must
      be obtained prior to conducting human subject research. Historically this was not
      the case, and human subjects were injured as a result. Because there has been and
      still remains an inevitable conflict of interest for researchers, instititions
      that perform human research must follow regulations designed to protect human
      subjects contained in the Code of Federal Regulations, if the research is
      federally funded. Two federal agencies provide oversight for IRB activities: the
      Food and Drug Administration (FDA) and a National Institutes of Health Office for
      Human Research Protection (OHRP), formerly the Office for Protection from
      Research Risks (OPRR). These agencies are charged with the implementation of
      rules related to ethical and legal obligations of researchers and their
      institutions. The institution's role, by means of an IRB, is to adhere to
      principles of the Belmont Report and to set forth ethical principles, policies,
      and procedures for protecting the rights and welfare of human subjects. The
      researchers' role is to conduct their research ethically while maximizing
      benefits and minimizing harm. Studies involving radiation exposure of human
      subjects add another level of risk that must be evaluated by an IRB with
      assistance of a radiation expert or radiation safety committee (RSC). This paper
      will look at regulatory aspects of human research, IRB responsibilities overall
      and as they relate to radiation exposure of subjects, and the role of the RSC.

PMID- 11316088
TI  - An innovative technique in scanning land areas with a multi-FIDLER system.
AB  - Remediation can be a long and tedious effort. One possible step in this process
      is the scanning of land to locate elevated areas of radiological contamination.
      By adapting existing global positioning technology with radiation detection
      systems, this process can be significantly accelerated. The Field Instrument for
      Detecting Low Energy Radiation (FIDLER) was used in conjunction with a Global
      Positioning System (GPS) and Trimble data logger. With this system two different
      land areas were scanned using two different scanning methods. In the first
      method, three FIDLERs were attached to a baby jogger and were used to scan a 20
      acre site devoid of vegetation. The second technique involved individuals
      carrying the instruments over a 15-acre site that contained vegetation. Here the
      FIDLERs were waved in front of the workers in 50-cm arcs. In all cases,
      radiological and position data were collected by the data loggers. Using these
      results, accurate maps were generated for each site clearly illustrating areas
      and spots of elevated activity. By employing this technique over 250,000 data
      points pertaining to position and count rate were used to map nearly 40 acres of
      land in under 3 wk.

PMID- 11316089
TI  - Consistency and efficiency of standard swipe procedures taken on slightly
      radioactive contaminated metal surfaces.
AB  - In radiation work areas, a standard "swipe" procedure is widely used to evaluate
      the extent of contamination on surfaces. This report documents the variability in
      results of swipes carried out on various metal surfaces and the variability
      between different experienced health physics technicians. Also, there is an issue
      of the efficiency of the first swipe in terms of what fraction of the total
      absorbed surface contamination is detected by a swipe. The samples used for this
      study were metal surfaces uniformly exposed in the spent fuel pool of a nuclear
      power plant The primary surfaces studied were those usually found on spent fuel
      transportation casks (mainly 304 stainless steel in the U.S.), which are
      submerged in the spent fuel pools for loading or unloading of the highly
      radioactive fuel assemblies from nuclear power plants. These surfaces become
      contaminated with suspended and dissolved radionuclides, primarily 137Cs, 134Cs,
      and 60Co, in the spent fuel pool. A detailed evaluation was conducted of
      variations in the swipe measurements made on these metal samples using repeated
      swipes of the same area by the same technician and comparing swipes of one
      technician to those of another on similar surfaces. Rough surface finishes showed
      considerable inconsistency (approximately 30% variation) from one technician to
      another, but smooth surface finishes show substantially better consistency (<10%
      variation) between technicians. The "efficiencies" of a single swipe,
      particularly the initial swipe, expressed as a fraction of total "removable"
      contamination, ranged from approximately 10% to 20% for the stainless steel and
      titanium surfaces. Aluminum surfaces, on the other hand, showed much higher
      efficiencies on the initial swipe. However, in terms of the total contamination
      imbedded in the surfaces, the first swipe picked up only between 0.5% and 3% of
      the total adsorbed contamination. The overall results show the wide variations
      that routinely occur in swipe results on portions of surfaces that would be
      expected to give consistent results. These difference are an order of magnitude
      or more greater than the counting statistical errors.

PMID- 11316090
TI  - Radiological impact on the workers, members of the public, and environment from
      the partial decommissioning of Pakistan Research Reactor-I and its associated
      radioactive residues.
AB  - The Pakistan Research Reactor-I (PARR-I) is a swimming pool type research reactor
      originally designed and built for a thermal power of 5 MW using High Enriched
      Uranium (HEU) fuel. In 1990-1991 the reactor was redesigned, partially
      decommissioned and recommissioned to operate with Low Enriched Uranium (LEU) fuel
      at a thermal power of 10 MW. An essential requirement, construction and
      commissioning of a wet spent fuel storage bay and fabrication of an irradiated
      fuel transfer cask were completed before actual dismantling of the reactor core.
      During the partial decommissioning operations, radioactive waste generated
      included 600 m3 low-level liquid radioactive waste and 14 m3 of solid radioactive
      waste with an average specific activity of 4.52 Bq ml(-1) and 2.22 kBq g(-1),
      respectively. External radiation doses of the workers were determined using TLD
      (NG 6,7) and direct reading dosimeters. The maximum individual external radiation
      dose received by any worker during this practice was 5 mSv, which was 25% of the
      annual dose limit of 20 mSv. Detection and measurement of internal contamination
      was carried out using bioassay techniques. During the whole operation, not a
      single case of internal contamination was detected. The ambient radiation levels
      around waste seepage pits are periodically monitored using TLD (G-2 cards) and G.
      M. radiation survey meters. Underground migration of radioactivity is checked by
      analyzing seepage water samples taken from boreholes that have been dug at
      different locations in the vicinity of the radioactive residues. The monitoring
      around disposal sites containing radioactive residues has been continued during
      the last 9 y and will be continued in the future. So far, no rise in the
      environmental gamma radiation dose level and migration of underground
      radionuclides has been found in the vicinity of these disposal sites. Working
      personal during the decommissioning of PARR-I have been found to be
      radiologically safe. Adherence to the ALARA principle, sound decommissioning and
      proper radioactive waste disposal procedures helped to protect the working
      personnel, members of the public, and the environment from the harmful effects of
      the ionizing radiations present due to the partial decommissioning of the
      research reactor and its radioactive residues. Experience gained during this
      work, along with the current international procedures, will be helpful for full
      restoration of the environment from radioactive residues likely to be generated
      in the future from any other practices in Pakistan.

PMID- 11316091
TI  - Intraocular pressure and silicone oil endotamponade.
AB  - PURPOSE: To evaluate intraocular pressure after instillation and eventual removal
      of silicone oil in patients undergoing pars plana vitrectomy combined with
      silicone oil endotamponade. METHODS: The study included 198 patients who
      underwent pars plana vitrectomy with silicone oil endotamponade (5,000 centistoke
      viscosity), in whom silicone oil was removed and in whom follow-up after oil
      removal was at least 3 months. All patients were operated on by one of two
      surgeons. RESULTS: After silicone oil instillation, intraocular pressure
      increased significantly (P < 0.001) from 12.9 +/- 4.4 mm Hg preoperatively to
      16.1 +/- 5.5 mm Hg postoperatively. Intraocular pressure was statistically (P >
      0.20) independent of the duration of silicone oil tamponade. Twenty percent of
      the 198 patients had at least one postoperative intraocular pressure measurement
      that was higher than 21 mm Hg. Main reasons for increased intraocular pressure
      were closed inferior iridectomy, iris neovascularisation, silicomacrophagocytic
      open-angle glaucoma secondary to silicone oil emulsification, and preoperative
      history of glaucoma. Glaucomatous optic nerve damage was detected in 14 (14 of
      198, 7.1%) eyes, including 8 eyes with preoperative antiglaucoma treatment.
      Silicone oil emulsification occurring in 40 (40 of 198, 20.2%) patients did not
      statistically influence intraocular pressure after oil removal. Ocular hypotony
      occurred in 10 (10 of 198, 5.1%) patients after oil release leading to
      intraocular hemorrhages and loss of vision in 3 patients. CONCLUSION: Clinically
      significant increased intraocular pressure after pars plana vitrectomy with
      silicone oil endotamponade occurs relatively rarely, can usually be well
      controlled by topical antiglaucoma medication, and is reversible in most patients
      after oil removal. In patients with increased intraocular pressure and silicone
      oil endotamponade, oil removal may be preferred to invasive antiglaucoma surgery
      to reduce intraocular pressure.

PMID- 11316092
TI  - Effect on intraocular pressure during 24 hours after repeated administration of
      the fixed combination of latanoprost 0.005% and timolol 0.5% in patients with
      ocular hypertension.
AB  - PURPOSE: To measure the effect on intraocular pressure (IOP) for 24 hours after
      repeated administration of the fixed combination of latanoprost 0.005% and
      timolol 0.5%. METHODS: A randomized, double-masked placebo-controlled crossover
      study including 20 patients with ocular hypertension was carried out. Patients
      were randomized to treatment with the fixed combination of latanoprost and
      timolol or with placebo. The eyedrop was taken at 8 AM. After 2 weeks of
      treatment, the patients were hospitalized, and the IOP was measured at 8 AM, and
      thereafter every other hour until midnight, and also at 3 AM, 6 AM, and 8 A.M.
      After a washout period of 4 weeks, they switched to the other eyedrop, and after
      2 weeks of treatment were hospitalized and the IOP measurements were repeated at
      the same intervals. RESULTS: The mean 24-hour IOP was 14.7 +/- 0.3 mm Hg (mean +/
      standard error of the mean) for latanoprost and timolol and 19.4 +/- 0.3 mm Hg
      for placebo. This corresponds to a significant IOP difference of 4.7 +/- 0.4 mm
      Hg (95% confidence interval 3.8-5.8; P < 0.001) between the two treatments in
      favor of the combination. At all measured time points, except at 3 AM, the mean
      IOP was lower with latanoprost and timolol than with placebo. During daytime
      measurements the mean IOP was 13.9 +/- 0.7 mm Hg for the fixed combination and
      19.5 +/- 0.7 mm Hg for the placebo. Corresponding figures at nighttime were 16.1
      +/- 0.7 mm Hg and 19.2 +/- 0.7 mmHg, respectively. CONCLUSIONS: The fixed
      combination of latanoprost and timolol significantly reduced IOP after
      administration once daily for 2 weeks in patients with ocular hypertension. A
      reduction of IOP during a 24-hour period was seen, with a greater IOP reduction
      during daytime compared with nighttime. The fixed combination applied once daily
      could be a convenient alternative to concomitant therapy with its individual
      components.

PMID- 11316093
TI  - Expanded polytetrafluoroethylene reinforcement material in glaucoma drain
      surgery.
AB  - PURPOSE: To determine whether a synthetic material, expanded
      polytetrafluoroethylene (E-PTFE), can be used successfully as a reinforcement
      material over the tubes of glaucoma drainage implants. METHODS: Patches of E-PTFE
      were sutured over the tubes of Baerveldt glaucoma drains implanted in the eyes of
      New Zealand white rabbits. Two material thicknesses were tested: 0.5 mm in four
      eyes and 0.25 mm in five eyes. Rabbit donor scleral patches were used in five
      eyes as the control. Total ocular health and intraocular pressure were monitored
      every 2 weeks after the procedure. Six months after implantation, the eyes were
      harvested and analyzed histologically. RESULTS: Two of the four eyes that
      received 0.5-mm thick E-PTFE patches showed some conjunctival melting over the
      anterior corners of the material close to the limbus. All five eyes that received
      0.25-mm thick E-PTFE patches showed a healthy cellular wound healing response and
      no conjunctival melting. Cellular infiltration and collagen deposition in the E
      PTFE materials showed integration of the patch material into the surrounding
      tissue. In the control eyes, marked thinning and resorption of the donor sclera
      immediately above the drainage tube was noted. CONCLUSION: Thin (0.25 mm) E-PTFE
      patches were well tolerated in all rabbit eyes tested. Thin E-PTFE should be
      investigated further as a functional alternative to donor sclera for
      reinforcement in glaucoma drain surgery.

PMID- 11316094
TI  - Mathematical and optimal clustering of test points of the central 30-degree
      visual field of glaucoma.
AB  - PURPOSE: To determine a mathematically optimal sector pattern of the central 30
      degree visual field for the follow-up of glaucomatous visual field change based
      on a large number of actual visual field test data of patients with glaucoma.
      METHODS: Visual field test data obtained from 1,039 eyes of 1,039 patients with
      open-angle glaucoma (OAG) using the 30-2 program of the Humphrey Field Analyzer
      were used for sectorization of the central 30 degree visual field. Of the 1,039
      visual field data, 698 (modeling data) were used for determining the sector
      pattern and 341 (testing data) for checking the sector pattern. The modeling data
      were further divided into three groups according to the mean deviation (MD) (MD >
      or = -10 dB, -20 < or = MD < -10 dB, and MD < -20 dB), and the sector pattern was
      constructed from visual field data of each group using a clustering procedure
      called VARCLUS. The testing data were used for determining the optimal sector
      pattern. In a separate set of repeated visual field data of 303 patients with
      OAG, the fluctuation of MD, sector values of each sector determined, and total
      deviation of each test point were calculated and compared. RESULTS: The sector
      pattern constructed from visual field data of MD > or = -10 dB summarized the
      visual field performance most effectively. The fluctuation of the sector value of
      each sector was roughly 1.5 times smaller than the total deviation of each test
      point. CONCLUSION: The sector pattern determined may be useful in analyses of the
      visual field data of patients with glaucoma.

PMID- 11316095
TI  - Management of the failing filter.

PMID- 11316097
TI  - Reflections and projections on crossing the millennium: Tenth American Glaucoma
      Society Lecture honoring Marvin L. Sears, MD.

PMID- 11316096
TI  - Dorzolamide-induced immune thrombocytopenia: a case report and literature review.
AB  - PURPOSE: To report a severe case of dorzolamide-induced immune thrombocytopenia,
      to review the literature on this topic, and to draw attention to the serious
      potential side effects of this topical sulfonamide. CASE REPORT: An 83-year-old
      man with primary open-angle glaucoma in both eyes who was taking topical
      dorzolamide therapy for 3.5 years developed a severe thrombocytopenia (10,000
      platelets/microL). The amount of platelets was not influenced by prednisone
      therapy but increased rapidly to 100,000/microL after the withdrawal of
      dorzolamide. LITERATURE REVIEW: Although the potential capacity of sulfonamides
      to induce thrombocytopenia is well known, no case of dorzolamide-induced immune
      thrombocytopenia was published in the medical literature until July 2000.
      CONCLUSION: Considering the possible severe side effects that can be induced by
      topical dorzolamide 2%, ophthalmologists should carefully evaluate during the
      medical history of their patients the risk of sensitivity to sulfonamides.

PMID- 11316098
TI  - Glaucoma associated with elevated episcleral venous pressure.

PMID- 11316099
TI  - Between a rock and a soft place.

PMID- 11316100
TI  - Transscleral contact krypton laser cyclophotocoagulation for treatment of
      posttraumatic glaucoma.
AB  - PURPOSE: To evaluate the usefulness of the krypton laser for transscleral contact
      cyclophotocoagulation in the treatment of posttraumatic glaucoma. PATIENTS AND
      METHODS: A total of 18 eyes of 18 patients with therapy-resistant posttraumatic
      glaucoma treated with krypton laser cyclophotocoagulation from 1991 to 1996 were
      included in this review. The krypton laser was delivered by a fiberoptic probe
      with simultaneous compression of the sclera. The energy used was 3 to 5 J per
      application at the tip of the probe, with an exposure time of 10 seconds. The
      treatment covered 90 to 360 degrees of the ciliary body with approximately 10
      applications per quadrant. RESULTS: With one or more cyclophotocoagulation
      treatments, the intraocular pressure decreased from the baseline mean (+/-
      standard deviation) of 32.6 +/- 12.8 mm Hg to 23.6 +/- 10.3 mm Hg (n = 17) at 1
      month, to 21.8 +/- 7.5 mm Hg (n = 13) at 3 months, to 22.5 +/- 7.6 mm Hg (n = 13)
      at 6 months, and to 19.6 +/- 10.5 mm Hg (n = 18) at the last control visit (mean,
      19.4 months; range, 3 weeks to 73 months) after cyclophotocoagulation but no
      other glaucoma procedure. At baseline, 17 (94%) of 18 patients were taking
      glaucoma medication, as were 15 (83%) of 18 patients at the last control visit.
      One (6%) case of phthisis occurred. CONCLUSIONS: Krypton laser
      cyclophotocoagulation is an effective and reasonably well tolerated means of
      lowering intraocular pressure in posttraumatic glaucoma. Because of the
      refractory nature of the disease, repeated treatments may be needed.

PMID- 11316101
TI  - Effects of early postfiltration ocular hypotony on visual acuity, long-term
      intraocular pressure control, and posterior segment morphology.
AB  - PURPOSE: To determine whether hypotony after filtration surgery has any influence
      on visual acuity and intraocular pressure (IOP) lowering. PATIENTS AND METHODS:
      We prospectively investigated 43 eyes of 43 patients undergoing trabeculectomy
      without the use of antimetabolites for 12 months. RESULTS: The lowest
      postoperative IOP valued 4.9 +/- 3.6 mm Hg (range, 0-14 mm Hg). It correlated
      statistically significant with the IOP 6 weeks (P = 0.016), 6 months (P = 0.009),
      and 1 year after surgery (P = 0.027). Eyes with a deterioration of visual acuity
      6 weeks after surgery had undergone a stronger postoperative hypotony
      (correlation with lowest postoperative IOP, P = 0.035). The mean period with an
      IOP less than 5 mm Hg was 3.5 +/- 8.0 days, and the mean period with an IOP less
      than 10 mm Hg lasted 45.4 +/- 68.8 days (range, 0-276 days). A hypotony score
      based on IOP and duration of hypotony was introduced. A correlation was detected
      between morphologic signs of hypotony, such as tiny retinal folds, at the 6-month
      follow-up and the duration of hypotony (P = 0.029) and hypotony score (P =
      0.001). CONCLUSIONS: Hypotony after filtration surgery may decrease visual acuity
      in the early postoperative period. Conversely, early postoperative hypotony
      correlated with better long term IOP control. There was no deleterious effect on
      visual acuity after 6 months.

PMID- 11316102
TI  - Immediate diode laser peripheral iridoplasty as treatment of acute attack of
      primary angle closure glaucoma: a preliminary study.
AB  - PURPOSE: To study the efficacy and safety of diode laser peripheral iridoplasty
      as a first-line treatment of acute primary angle-closure glaucoma (PACG) without
      the use of systemic anti-glaucoma medications. PATIENTS AND METHODS: Nine
      consecutive patients with acute PACG were recruited into the study. Each patient
      received topical pilocarpine (4%), timolol (0.5%), apraclonidine (1%), and
      immediate diode laser peripheral iridoplasty as primary treatment. The
      intraocular pressures (IOPs) 15, 30, and 60 minutes after diode laser peripheral
      iridoplasty were documented by Goldmann applanation tonometry. RESULTS: The mean
      IOP of this group of patients was reduced from 66.3 +/- 9.7 mm Hg, before diode
      laser peripheral iridoplasty, to 36.6 +/- 16.4 mm Hg at 15 minutes, 26.3 +/- 12.6
      mm Hg at 30 minutes, and 18.9 +/- 8.4 mm Hg at 60 minutes after diode laser
      peripheral iridoplasty. In seven of the nine patients, the corneal edema cleared
      up 1 hour after diode laser peripheral iridoplasty. In the remaining patient, the
      cornea cleared up 12 hours after diode laser peripheral iridoplasty. No
      significant complications were encountered. CONCLUSION: Diode laser peripheral
      iridoplasty, together with topical antiglaucoma medications without adjunctive
      systemic carbonic anhydrase inhibitors and hyperosmotic agents, appeared to be
      effective and safe in controlling the IOP in acute PACG.

PMID- 11316103
TI  - Ability of peripapillary atrophy parameters to differentiate normal-tension
      glaucoma from glaucomalike disk.
AB  - PURPOSE: To investigate the ability of peripapillary atrophy (PPA) parameters to
      differentiate normal-tension glaucoma (NTG) from glaucomalike disk (GLD).
      METHODS: Thirty-three eyes of 33 patients with GLD that had no evidence of visual
      field defect and retinal nerve fiber layer defect and 33 eyes of 33 patients with
      NTG, matched with age and intraocular pressure, were enrolled. The participants
      were selected from the database of patients referred from a routine health
      checkup because of high cup-to-disk ratio (>0.5). Topographic measurements for
      the optic disk were performed using the Heidelberg Retina Tomograph (HRT). The
      extent of PPA (zone beta) was measured with Atrophy Zone Analysis software of
      HRT. Receiver operating characteristic (ROC) curves (GraphROC version 2.0) were
      used to compare the new formula including PPA parameters with that of the HRT
      discriminant analysis formula in differentiating NTG from GLD. RESULTS: The area
      of zone beta, atrophy-to-disk area ratio, and angular and radial extent of zone
      beta were significantly larger in NTG (P < 0.01). Multiple logistic regression
      analysis showed that rim area and corrected radial extent of zone beta are
      variables that show significant difference between NTG and GLD (P < 0.05). The
      area under the ROC curve for the new formula including rim area and corrected
      radial extent of zone beta (0.8655) was significantly larger than that for the
      HRT discriminant analysis formula (0.7351) (P = 0.0128). CONCLUSION: The PPA
      measurement obtained by HRT can be a useful additional tool to differentiate NTG
      from GLD after the first screening by disk photograph in a routine health
      checkup.

PMID- 11316104
TI  - In vitro secretion of cytokines and prostaglandin-E2 by monocytes from lung
      cancer patients.
AB  - Monocytes (MO) from cancer patients present functional abnormalities, such as an
      altered secretion of soluble factors. In the present study, our aim was to
      evaluate the levels of interleukin-1beta (IL-1beta), tumour necrosis factor-alpha
      (TNF-alpha) and prostaglandin-E2 (PGE2) secreted in vitro by MO from lung cancer
      patients (LCP), spontaneously or after stimulation with lipopolysaccharide (LPS).
      Results showed that cytokine secretion was higher for MO from LCP than for MO
      from healthy controls, while in the 25% of the patients analysed, an absence of
      response to LPS treatment was found.

PMID- 11316105
TI  - Relevance of dyspnoea and respiratory function measurements in monitoring of
      asthma: a factor analysis.
AB  - Previous studies in patients with stable chronic obstructive pulmonary disease
      have demonstrated that objective measures (lung volumes and respiratory muscle
      force) and clinical or subjective measures (symptoms of breathlessness and
      exercise tolerance) are quantities that independently characterize the conditions
      of these patients. Such an evaluation has not been previously applied in patients
      with stable bronchial asthma. Sixty-nine patients with stable chronic asthma
      underwent evaluation of static (functional residual capacity, FRC) and dynamic
      [forced expiratory volume in 1 sec (FEV1) and forced vital capacity, FVC] lung
      volumes; respiratory muscle strength (RMS), by measuring maximal inspiratory and
      expiratory pressures, and exercise capacity by means of the 6-min walking
      distance (6MWD). Chronic exertional dyspnoea was assessed by the Baseline
      Dyspnoea Index (BDI) focal score and by the Medical Research Council (MRC) scale.
      Statistical evaluation was performed by applying factor analysis. Three factors
      accounted for 78% of the total variance in the data: FEV1, FVC loaded on a factor
      I; RMS, FRC and 6MWD loaded on a factor II; dyspnoea ratings loaded on a factor
      III. Post-hoc analysis by randomly dividing the patients into two subgroups gave
      the same results. In asthmatic patients, airway obstruction appeared as an
      independent dimension or factor. Dyspnoea independently characterized the
      condition of asthma. Submaximal exercise tolerance could not be associated with
      the symptom of breathlessness. Evidence of independent factors support the
      validity of routine, multi-factorial assessment and the primary goal of treatment
      to alleviate symptoms and improve functional capacity in stable asthmatics.

PMID- 11316106
TI  - The apparent response of airway function to deep inspiration depends on the
      method of assessment.
AB  - The response to deep inspiration (DI) has been reported in terms of specific
      airway conductance (SGaw) pre- and post-DI, and by comparing forced expiratory
      flows following both maximal and partial inspiration (M/P ratio). The lung volume
      at which M/P has been obtained has varied between studies. We have investigated
      how the method of assessment affects the apparent response to DI. In 16 asthmatic
      and 16 control subjects both SGaw and M/P were measured, the latter at various
      lung volumes from 40 to 15% vital capacity (VC) (remaining). In each group M/P
      increased as lung volume decreased (r=-0.98, P<0.001 for each group). In
      contradistinction to M/P ratio, the SGaw ratio (post-DI: pre-DI) suggested a
      bronchoconstrictor asthmatic response (mean 0.938, SEM 0.029) and a
      bronchodilator control response (mean 1.063, SEM 0.029). SGaw ratio and M/P were
      correlated strongly in normals but not in asthmatics. These results confirm that
      the observed response to DI depends on the method used to measure it. The results
      in normals are explicable by DI-induced smooth muscle stretch increasing
      unstressed airway calibre, but also increasing compressibility on forced
      expiration. The results in asthma suggest the existence of an additional DI
      related bronchoconstricting mechanism.

PMID- 11316107
TI  - Secular trends of allergic asthma in Danish adults. The Copenhagen Allergy Study.
AB  - Numerous studies have reported increases in asthma prevalence among children
      world-wide. Less is known about similar trends in adults. We aimed to investigate
      whether the prevalence of allergic asthma symptoms had increased in an adult
      general population. Two cross-sectional surveys using identical methods were
      carried out in 1989 and 1998. A one-page questionnaire on respiratory symptoms
      was mailed to random samples of 15-41-year-olds living in Copenhagen. The
      response rates were 86.6% (3624/4185) and 78.8% (2402/3048) in 1989 and 1998,
      respectively. The questionnaire was validated with specific immunoglobilin E
      (IgE) positivity as the reference in a random sample of responders in connection
      with both surveys. We found a significantly increased prevalence of subjects who
      reported shortness of breath on exposure to pollens (6.6% 0 s. 10.3%, odds ratio
      1.61, 95% CI 1.34-1.95), furry animals (5.4% vs. 7.6%, odds ratio 1.45, 95% CI
      1.17-1.79), and house dust (7.8% vs. 10.2%, odds ratio 1.35, 95% CI 1.12-1.61).
      The validation of these symptoms showed that the positive predictive values were
      reasonably stable over time, which may support that a true increase in allergic
      asthma has occurred. In conclusion, the prevalence of allergic asthma symptoms
      increased significantly in this adult general population over a 9-year period.

PMID- 11316108
TI  - The role of domiciliary nebulizers in managing patients with severe COPD.
AB  - The difficulty of assessing nebulizer responses in chronic obstructive pulmonary
      disease (COPD) has been demonstrated before. This study aims to re-examine both
      the role of domiciliary nebulizers in COPD and also bronchodilator (BD)
      assessment in individuals. In a double-blind, randomized, cross-over trial, 19
      stable patients with severe COPD were given the following medication 6-hourly for
      2-week periods: (1) nebulized salbutamol 2.5 mg with ipratropium 0.5 mg and
      placebo inhalers (MDI) with spacer; (2) placebo nebules and inhaled salbutamol
      400 microg with ipratropium 80 microg via MDI with spacer; (3) inhaled salbutamol
      400 microg with ipratropium 80 microg via MDI with spacer (but no placebo
      nebulized drugs). Both nebulized and MDI drugs produced highly significant
      improvements in forced expiratory volume in 1 sec (FEV1), forced vital capacity
      (FVC), specific airways conductance, 6-min walking distance (6MWD) and residual
      volume. There were no significant differences between BD responses obtained after
      active nebulized and active MDI BDs. From the diary cards, 2 weeks of active
      nebulized BDs produced a slightly higher median peak expiratory flow (PEF) than
      active MDI BDs (236 and 219 l m(-1), respectively, P=0.01) and slightly less
      extra inhaler use (0.8 and 1.1 puffs, respectively, P<0.05) but no significant
      difference in dyspnoea or quality of life (QOL) scores. There were significant
      correlations between domiciliary PEF and acute BD-induced changes in FVC and
      6MWD, and also between domiciliary dyspnoea scores and acute changes in both
      total lung capacity and 6MWD. In conclusion, nebulized medication conferred
      little clinical advantage over the regular use of inhalers with spacers in this
      group of patients with severe COPD. However, acute changes in total lung
      capacity, FVC and 6MWD may be useful predictors of the longer-term effects of
      nebulized BDs in individual patients.

PMID- 11316109
TI  - The effect of ribavirin to treat previously healthy infants admitted with acute
      bronchiolitis on acute and chronic respiratory morbidity.
AB  - The role of ribavirin in the treatment of acute bronchiolitis is controversial.
      It has been suggested that the use of ribavirin may be of benefit during the
      acute illness and may reduce subsequent recurrent respiratory morbidity. This
      randomized, double-blind, placebo-controlled study was designed to determine
      whether ribavirin administered during the acute illness would have an influence
      on respiratory morbidity during both the acute illness and during the following
      year. Bronchial reactivity 6 months after the acute illness was also assessed.
      Forty previously well infants with moderately severe acute bronchiolitis were
      recruited during three winter epidemics. Subjects received study medication for
      18 h a day. Management was otherwise unaltered. Subjects were evaluated daily by
      the investigator and subsequently assessed at 6 weeks, 6 months and 1 year
      following the acute illness. Assessment of bronchial hyper-responsiveness was
      assessed at 6 months of age using total body plethysmography and an established
      ultra-sonically nebulized distilled water challenge. A total of 40 patients (21
      ribavirin, 19 placebo) were entered into the study. The two groups did not differ
      with respect to age, gender or clinical severity on entry to the trial. No
      significant differences were identified in the rate of clinical improvement over
      the first 24 h, the time to discharge, bronchial responsiveness at 6 months of
      age, frequency of significant respiratory symptoms over the first year of life
      and the frequency of prescribed bronchodilators and inhaled steroids during the
      year of follow-up. This study was unable to demonstrate any clinical benefit from
      the use of ribavirin in the acute illness or during subsequent follow-up for 1
      year.

PMID- 11316110
TI  - Chest mechanics in morbidly obese non-hypoventilated patients.
AB  - Seventy-seven patients with morbid obesity, body mass index (BMI) 40-69.9 kg m(
      2), who were candidates for gastroplasty, were studied in our laboratory as part
      of a pre-operative survey. They had no complaints other than obesity and were not
      cyanotic. A group of 28 lean subjects (BMI 20-29.8 kg m(-2)) who were candidates
      for abdominal surgery, without any respiratory complaint, were included as
      controls. For each patient a pulmonary function test was performed, measuring
      slow vital capacity with expiratory residual volume (ERV), forced vital capacity
      (flow/volume) and maximal voluntary ventilation (MVV). In obese patients the MVV
      is reduced as BMI increases. This results in the reduction of expiratory flows
      and volumes. Forced expiratory volume in 1 sec (FEV1) is reduced in proportion to
      the FVC reduction and is related to MVV. It is suggested that the main
      consequence of the burden of the chest wall by increased adipose mass is a
      reduction in its compliance, making inspiration increasingly difficult, and
      resulting in lower static volumes and flows.

PMID- 11316111
TI  - The short-term repeatability of histamine bronchial testing in young males. The
      SUS study.
AB  - We have measured bronchial responsiveness (BR) to histamine on two occasions
      between 5 and 24 h apart, to determine if conventional and new indices of BR are
      repeatable. A random sample of 29 healthy male subjects with a mean age of 19 (SD
      3.44) years from a larger study repeated a Yan method test of BR, recording both
      partial and maximal expiratory flow volume (PEFV and MEFV) curves. From the MEFV
      curves log-dose slopes (LDS) for forced expiratory volume in 1 sec (FEV1), forced
      expiratory flow between 25% and 75% of forced vital capacity (FVC) (FEF(25-75%)),
      mean expiratory flow at 30% and 40% of FVC (MEF30, MEF40), and the first moment
      of the spirogram (alpha1) truncated at 75% and 90% of FVC were calculated, as
      well as the provocative dose that induces a 20% fall in FEV1 (PD20FEV1). From the
      PEFV curves LDS for alpha(1)75% and alpha(1)90%, and MEF30 and MEF40 were
      derived. Apart from MEF30 and alpha(1)90% the second test was significantly lower
      (P<0.05) than the first when measuring the repeatability of spirometric indices,
      whereas the LDS of the indices showed no significant change. The repeatability
      expressed as intra-class correlation coefficient (ICC) was highest for LDS FEV1
      (0.87), second highest for LDS MEF40 (0.67) and LDS MEF30 (0.65). The LDS for
      moment indices were much less repeatable and the lowest ICC was found in all LDS
      indices derived from PEFV curves. Within-subject variance was not influenced by
      atopic status, smoking habits or recordable PD20FEV1. As tests for bronchial
      hyper-responsiveness (BHR) the LDS of FEV1, MEF40 and MEF30 seem to be acceptable
      for use in population studies.

PMID- 11316112
TI  - Diagnostic yield of computed tomography and densitometric measurements of the
      lung in thoracoscopically-defined idiopathic spontaneous pneumothorax.
AB  - In the present study, the diagnostic yield of high resolution computed tomography
      (HRCT) is evaluated in patients with thoracoscopically-verified idiopathic
      spontaneous pneumothorax (SP). Visual assessment as well as densitometry of lung
      parenchyma was performed. In eight of the 20 prospectively-evaluated SP patients,
      emphysema-like (EL) changes such as blebs and bullae could be detected. The SP
      patients with EL changes were significantly older and were more heavy smokers.
      Spirometrically-controlled CT lung densitometry showed no differences between the
      patient group with or without these EL changes. Comparing the densitometric
      measurements of the patient group with a healthy control group no significant
      differences in densitometry between both groups were found. In conclusion, this
      study confirms that HRCT is a reliable method of detecting blebs and bullae in
      patients with spontaneous pneumothorax. Furthermore CT lung densitometry revealed
      no parenchymal abnormalities or signs of air trapping in patients with
      spontaneous pneumothorax.

PMID- 11316113
TI  - Ethnic differences in anthropometry among adult Singaporean Chinese, Malays and
      Indians, and their effects on lung volumes.
AB  - When standing height (StndHt) cannot be assessed, arm span (AS) or sitting height
      (SitHt) has been used as surrogate variables for prediction of StndHt in adult
      caucasians and blacks. We examined (1) the relationship between StndHt, AS and
      SitHt among adult Chinese, Malays and Indians; and (2) whether anthropometry
      could explain the ethnic differences in lung volumes (as StndHt-adjusted lung
      volumes are known to differ significantly: Chinese > Malays > Indians). We
      recruited 1250 consecutive outpatients aged 20-90 years. Prediction equations of
      StndHt (with AS, SitHt, weight, age as predictors) for each subgroup of race and
      sex were formulated with multiple linear regressions. Equations with both AS and
      SitHt as predictors had the best goodness of fit (SEE = 2.37-2.85 cm, adjusted R2
      = 0.67-0.87), as compared to equations with either AS (SEE = 3.00-3.91 cm,
      adjusted R2 = 0.58-0.80) or SitHt alone (SEE = 3.48-4.00 cm, adjusted R2 = 0.45
      0.76). GLM general factorial analyses found that age- and weight-adjusted SitHt
      to-StndHt ratios differed significantly among Chinese (0.539), Malays (0.529) and
      Indians (0.518). This paralleled the ethnic differences in lung volumes. The
      equations with both AS and SitHt as predictors provide the most accurate estimate
      of StndHt. Ethnic differences in upper body segment length may explain in part
      the lung volume differences.

PMID- 11316114
TI  - Coccidioidomycosis in non-endemic areas: a case series.
AB  - Coccidioidomycosis is a systemic infection caused by the soil fungus Coccidioides
      immitis, which is endemic to the south-western United States. Manifestations
      range from flu-like illness to pneumonia and septic shock. Diagnosis may be
      delayed or missed in non-endemic areas because of the low index of suspicion. We
      describe a series of 23 patients with coccidioidomycosis at one institution in a
      non-endemic area. Diagnosis was often delayed. In two patients, the route of
      exposure could not be determined, but 20 patients had a history of residence or
      travel to endemic areas, and the remaining patient had an occupational history of
      exposure to fomites from an endemic region. Five patients were immunosuppressed.
      Most patients responded well to medical therapy, surgery, or both. Although
      coccidioidomycosis is rare in non-endemic areas, physicians must keep it in mind
      when evaluating patients who have traveled to endemic areas or who are
      immunosuppressed.

PMID- 11316115
TI  - New developments in echocardiography: impact on coronary artery disease.

PMID- 11316116
TI  - Coronary lesion morphology and prognosis in young males with myocardial
      infarction with or without familial hypercholesterolemia.
AB  - The present study examined the angiographic characteristics and prognosis of
      young males under 40 years of age with acute myocardial infarction (AMI) and
      familial hypercholesterolemia (FH). The study group was divided into an FH group
      (n=16) and a non-FH group (n=27). Lesion morphology was classified as complex or
      smooth. Overall 36 patients were followed up for an average of 9.4 years. The
      frequency of angiographic normal or nonobstructive culprit lesions was
      significantly higher in the non-FH group (p<0.01). In contrast, the incidence of
      complex or totally occlusive lesions was higher in the FH group (p<0.01). At 10
      year follow-up, survival rates from cardiac death (FH 85% vs non-FH 100%,
      p=0.06), from AMI (FH 43% vs non-FH 80%, p<0.05), and from any ischemic event at
      a new lesion (FH 9% vs non-FH 67%, p<0.01) were all reduced in the FH group.
      These results suggest that the mechanism of AMI in young male patients with FH
      differs from that in similar aged patients without FH, and that the overall
      prognosis of these patients is less favorable.

PMID- 11316117
TI  - Combined revascularization strategy for acute myocardial infarction in patients
      with intracoronary thrombus: preceding intracoronary thrombolysis and subsequent
      mechanical angioplasty.
AB  - Thrombus in the infarct-related artery is one of the limitations for flow
      restoration in primary percutaneous transluminal coronary angioplasty (PTCA)
      treatment for acute myocardial infarction (AMI). The present study investigated
      the benefit of preceding intracoronary thrombolysis (ICT) by retrospectively
      analyzing acute phase flow restoration in 80 AMI patients with intracoronary
      thrombus: 40 undergoing primary PTCA alone (primary PTCA group) and 40 treated
      with preceding ICT plus PTCA (combined group). Acute phase Thrombolysis in
      Myocardial Infarction (TIMI) grade flow was as follows: TIMI 0/1: 35.0% vs 12.5%
      for the primary PTCA group and the combined group, p=0.06; TIMI 2: 7.5% vs 15.0%,
      p=NS; TIMI 3: 57.5% vs 72.5%, p=NS). In the subgroup analysis, it was also less
      in the combined group among 33 patients with a left anterior descending coronary
      artery (LAD) lesion (42.1 % vs 7.1%, p=0.08), but not among the remaining 47 with
      either a right coronary artery or left circumflex artery lesion. The combined
      therapy may potentially provide better acute phase flow restoration in AMI
      patients with an intracoronary thrombus in a LAD lesion.

PMID- 11316118
TI  - Triple valve replacement with bileaflet mechanical valves: is the mechanical
      valve the proper choice for the tricuspid position?
AB  - A more durable mechanical valve may be a better choice for the tricuspid position
      than a bioprosthesis when the patient already has mechanical prosthesis in the
      left side of the heart. Eleven cases of triple valve replacement (total follow-up
      period, 49.5 patient years), all with mechanical valves, are reviewed to assess
      optimal valve selection. Nine patients had undergone a total of 12 previous
      cardiac surgeries. Three patients died in hospital (27.3%), but there were no
      late deaths among the survivors. Two cases of valve thrombosis in the tricuspid
      position occurred (linearized incidence: 4.04%/patient years) and 1 of these
      required reoperation. Because of this high incidence of valve thrombosis, the
      bileaflet mechanical valve is not considered to be the best choice. Even if
      mechanical valves are implanted in the left side of the heart, a bioprosthesis
      may be a better choice at the tricuspid position.

PMID- 11316119
TI  - Plasma monocyte chemoattractant protein-1 antigen levels and the risk of
      restenosis after coronary stent implantation.
AB  - Monocyte chemoattractant protein-1 (MCP-1) plays a fundamental role in monocyte
      recruitment and has been implicated in atherosclerosis. The present study tested
      the hypothesis that increased levels of MCP-1 are associated with an increased
      risk for restenosis post stent implantation. The plasma MCP-1 antigen levels were
      measured pre-stenting, and at 24 and 48 h and 6 months post stenting in 41
      patients with stable exertional angina (SEA) who had undergone successful stent
      implantation. Nineteen patients with chest pain syndrome were selected as a
      control group. Initial plasma MCP-1 antigen levels (mean +/- SE, pg/ml) in the
      patients with SEA were significantly higher than those in the control group
      (852.3+/-51.4 vs 418.2+/-26.7, p<0.001). The patients with SEA were divided into
      2 groups based on follow-up angiographic findings: 17 patients with restenosis (R
      group); 24 patients without restenosis (N group). The lesion was significantly
      longer in the R group than in the N group (p<0.03). Plasma MCP-1 antigen levels
      at pre-stenting were not significantly different between the 2 groups (820.6+/
      69.1 in the R group vs 874.7+/-73.8 in the N group). Serial changes of plasma MCP
      1 levels were plotted as percent changes from the initial levels (mean +/- SE, %)
      and were significantly higher in the R group than in the N group at 48 h and at 6
      months post stent implantation (104.6+/-4.8 vs 89.2+/-3.4, p<0.01, 109.6+/-11.2
      vs 98.5+/-5.0, p<0.05). The study concludes that MCP-1 production at stented
      coronary arterial sites is associated with an increased risk for restenosis post
      stent implantation.

PMID- 11316120
TI  - Short-term outcome of stent implantation in saphenous vein grafts: predictors of
      distal embolization and restenosis.
AB  - The present study, which aimed to determine the predictors of distal embolization
      and restenosis after stenting for vein graft disease, retrospectively analyzed 51
      consecutive patients who underwent stent implantation for diseased saphenous vein
      grafts. Follow-up angiography was performed 6 months after the procedure and the
      clinical and angiographic variables were analyzed by multivariate logistic
      regression to determine the predictors of distal embolization and restenosis.
      Initial clinical success was achieved in 49 patients, 44 of whom underwent follow
      up angiography and were enrolled in the retrospective analysis. Distal
      embolization occurred in 6 grafts (13.6%). Multivariate analysis showed that the
      lesion length and the total cholesterol level were independent predictors of
      distal embolization. Angiographic restenosis occurred in 13 (26.5%) of 49
      lesions. The minimum luminal diameter and the percent diameter stenosis after
      stenting were associated with the occurrence of restenosis. Multivariate analysis
      of lesions located in the graft body identified graft age as an independent
      predictor of restenosis. Distal embolization can occur after vein graft stenting,
      especially in patients with hypercholesterolemia and diffuse stenosis. The post
      stenting minimum luminal diameter and the percent diameter stenosis are
      predictors of restenosis. In particular, graft age is associated with the
      restenosis of graft body lesions.

PMID- 11316121
TI  - Effect of low-intensity warfarin therapy on left atrial thrombus resolution in
      patients with nonvalvular atrial fibrillation: a transesophageal
      echocardiographic study.
AB  - The presence of left atrial thrombus (LAT) is associated with an increased risk
      of embolic stroke. However, it has yet to be established definitively whether low
      intensity warfarin therapy (INR: 1.5-2.0) can prevent LAT formation in patients
      with nonvalvular atrial fibrillation (NVAF). The present study analyzed the
      clinical and transesophageal echocardiography (TEE) features of 123 such patients
      to identify risk factors for LAT formation and the efficacy of prophylactic low
      intensity warfarin therapy. Left atrial thrombi were found in 35 patients (28%)
      in whom systemic hypertension (49% vs 23%; p<0.01) and ischemic heart disease
      (17% vs 3%; p<0.01) were more frequent. Left ventricular ejection fraction (54+/
      14% vs 60+/-11%; p<0.05), left ventricular end-diastolic dimension (51+/-7 mm vs
      48+/-5 mm; p<0.05), spontaneous echo contrast (2.2+/-0.7 vs 1.4+/-0.9; p<0.01),
      left atrial diameter (50+/-6 mm vs 43+/-7 mm; p<0.01), left atrial appendage
      blood velocity (22.3+/-8.7 cm/s vs 37.2+/-21.5 cm/s; p<0.01) and the incidence of
      left ventricular hypertrophy (37% vs 15%; p<0.01) were also significantly
      different between the groups. Fourteen patients received continuous warfarin
      therapy (target INR: 1.5-2.0) and on the follow-up TEE study the left atrial
      thrombus resolved in 10 (71%). There were no thromboembolic events or major
      hemorrhagic complications in these patients, so it was concluded that low
      intensity warfarin therapy is efficacious in treating LAT formation in patients
      with NVAF.

PMID- 11316122
TI  - Multicenter prospective nonrandomized study of long-term antiarrhythmic drug
      therapy in patients with tachyarrhythmias: Japanese Antiarrhythmics Long-Term
      Study-2 (JALT-2 Study).
AB  - Based on the results of the Cardiac Arrhythmia Suppression Trial (CAST),
      strategies for the treatment of tachyarrhythmias have changed rapidly. The
      Japanese Antiarrhythmics Long-Term (JALT) study was planned to investigate the
      present methods for choosing antiarrhythmic drugs, and the effects on long-term
      prognosis in patients with tachyarrhythmias in Japan. Following a 6-month
      preliminary study (JALT-1), there was a multicenter nonrandomized prospective
      study (JALT-2), with a 2-year follow-up, of patients with paroxysmal atrial
      fibrillation (PAF), sustained ventricular tachycardia (SVT) and nonsustained VT
      (NSVT). Four hundred fifty-five patients were registered, and 361 of them (79%)
      were analyzed. Cerebral infarction occurred in 10 of 193 patients (5.2%) with
      PAF. Transition to chronic AF was observed in 21 patients (10.9%), but in none of
      the patients receiving Ca antagonist therapy. Twenty-five patients died: 5 deaths
      were arrhythmic, 10 were because of pump failure, and 9 were noncardiac. The most
      significant difference in drug selection between JALT-1 and JALT-2 was the
      increase in the use of slow kinetic Na channel blockers for PAF and the decrease
      in the use of the same agents for VT in the JALT-2 study. A marked change of
      therapeutic strategy occurred in JALT-2 compared with JALT-1. Most patients with
      a poor prognosis had underlying heart diseases and heart failure, but the per
      annum rate of death by arrhythmia and pump failure in JALT-2 was less than that
      in JALT-1.

PMID- 11316123
TI  - Platelet aggregability under shear is enhanced in patients with unstable angina
      pectoris who developed acute myocardial infarction.
AB  - The study investigated whether patients hospitalized for unstable angina pectoris
      (UAP), who subsequently develop complete coronary thrombosis (acute transmural
      myocardial infarction (AMI)) despite medical treatment, exhibit platelet
      hyperaggregability in an assay system that does not employ agonist stimulation.
      The study comprised 89 patients with UAP (Braunwald type B). Unfractionated
      heparin and nitrate were administered to all patients via continuous intravenous
      drip together with aspirin taken orally. Citrated platelet-rich plasma (230-250x
      10(3)/microl) was obtained on admission and again, in some patients, following
      the AMI. Platelet aggregability was measured in an optically modified cone-plate
      viscometer that enables the detection of platelet aggregation without agonist
      stimulation. A continuous shear rate of 1,200/s was employed. Of the 89 patients,
      85 were finally stabilized, while 4 developed an AMI accompanied by persistent ST
      segment elevation with increased levels of plasma creatine kinase within 3 h
      after starting the treatment. The extent of platelet aggregation on admission was
      significantly greater in these 4 patients compared with the 85 who were
      stabilized (87.8+/-6.8%, n=4 vs 26.8+/-9.1%, n=85; mean+/-SD). These data suggest
      that platelet hyperaggregability mediated mainly by fibrinogen binding to the
      activated glycoprotein IIb/IIIa complex occurs before a complete thrombotic
      occlusion and this evaluation may provide important information before the onset
      of myocardial infarction.

PMID- 11316124
TI  - Subacute and chronic effects of DDD pacing on left ventricular diastolic function
      in patients with non-obstructive hypertrophic cardiomyopathy.
AB  - The present study examined the ability of dual-chamber (DDD) pacing to improve
      symptoms and exercise tolerance in patients with non-obstructive hypertrophic
      cardiomyopathy (HNCM). Seven patients with HNCM who had failed to benefit from
      pharmacotherapy participated in the study. The New York Heart Association (NHYA)
      functional class status and exercise tolerance, which was determined by the
      treadmill exercise test, were recorded and an echocardiographic observation was
      performed before, and 1 week, 3 months and 1 year after the implantation of a
      permanent DDD pacemaker. The atrioventricular delay (AVd) was determined by
      measuring the point of peak rapid filling velocity and maximum cardiac output
      (CO). Two patients were not implanted with a permanent pacemaker because their CO
      and blood pressure decreased or because palpitation occurred during temporary
      pacing. The ratio between early and late peaks of flow velocity (1.56, 1.21,0.95,
      and 0.86 before implantation and 1 week, 3 months and 1 year after implantation,
      respectively); deceleration time (ms: 263.2, 217.6, 204.6, 187.0); peak filling
      rate (ml/s: 146.2, 204.0, 233.2, 243.6); NYHA functional class status (2.0, 1.8,
      1.6, 1.4); and exercise tolerance (s: 203, 264, 403, 480) were significantly
      improved after implantation. However, left ventricular dimension, percent
      fractional shortening, ejection fraction, acceleration time and the isovolumic
      relaxation time were not changed significantly. In conclusion, DDD pacing
      improved symptoms and the NYHA functional class status, which is associated with
      improvement of left ventricular diastolic function. It is proposed that DDD
      pacing would be useful in patients not only with obstructive but also non
      obstructive hypertrophic cardiomyopathy refractory to medical treatment,
      depending on the careful selection of subjects.

PMID- 11316125
TI  - Heart transplantation and the Batista operation for children with refractory
      heart failure.
AB  - Medically refractory heart failure may be present in children with cardiomyopathy
      (CMP) or complex congenital heart disease (CHD). In adults, the surgical
      management of this condition is either heart transplantation or the Batista
      operation. From March 1995 to January 2000, a total of 6 children, aged from 1 to
      16 years, with medically refractory heart failure associated with CMP or complex
      CHD underwent cardiac transplantation and one of them also had the Batista
      operation as a bridge to transplantation. One of the 6 patients died of
      intractable sepsis 17 days after the operation, but the other 5 were discharged
      with satisfactory hemodynamics. Immunosuppressive agents, including azathioprine,
      cyclosporin or FK-506, were given. One patient experienced moderate acute
      rejection, but it was controlled by FK-506, OKT-3 and solumedrol. However,
      another suffered from lymphoproliferative disease 8 months after transplant, but
      it was controlled by intravenous immunoglubulin, alpha-interferon and acyclovir.
      Cardiac function during serial follow-up (range, 1 month to 5 years) revealed
      normal systolic and diastolic function and none received any anticongestive
      medications. Almost all patients received an oversized donor heart. The left
      ventricle (LV) mass was remodeled, initially as an decrease and later as an
      increase. The patient who underwent the Batista operation was discharged 1 month
      after the operation with an increased LV ejection fraction (from 10% to 22%). She
      was successfully bridged to heart transplantation 7 months after the Batista
      operation. The results of cardiac transplantation in growing children are
      satisfactory and remain the mainstay of surgical treatment for medically
      refractory heart failure in these patients. However, with a shortage of donor
      hearts, the Batista operation may be adopted as a bridge to heart transplant with
      a fair response.

PMID- 11316126
TI  - Activation-recovery intervals of 12-lead electrocardiograms before and after
      catheter ablation in patients with Wolff-Parkinson-White syndrome.
AB  - Preexcitation in Wolff-Parkinson-White syndrome (WPW) has been reported to induce
      long-lasting changes in ventricular recovery properties. However, there has not
      been a report concerning changes in the activation-recovery interval (ARI) in 12
      lead ECGs before and after catheter ablation (CA) in patients with WPW syndrome.
      The present study compared changes in ARIs from 12-lead ECGs with those from body
      surface unipolar leads before and after CA to examine whether ARIs from limb
      leads of 12-lead ECGs provide useful information on changes in recovery
      properties in addition to the ARIs from precordial leads. The study population
      consisted of 27 manifest WPW patients with a left- (n=18, group A) or right-sided
      accessory pathway (n=9, group B). ARIs in leads I, II, and III were strongly
      correlated with those in unipolar leads over the left lateral, left lower, and
      right lower chest, respectively. ARIs in leads aVR, aVL, and aVF showed a
      significant correlation with those in unipolar leads over the right upper, left
      upper, and lower anterior chest, respectively. These correlations were maintained
      before and after CA. Furthermore, in group A, ARIs in lead V1 tended to increase
      on day 7 post CA compared with before CA and on day 1. In group B, ARIs in lead
      III significantly decreased on day 7 compared with before CA and on day 1. These
      findings suggest that ARIs from the limb leads of 12-lead ECGs may represent
      those from unipolar leads of a particular area over the body surface, and that
      ARIs from 12-lead ECGs may provide useful quantitative information on changes in
      recovery properties before and after CA in patients with manifest WPW syndrome.

PMID- 11316127
TI  - Response of the stroke volume and blood pressure of young patients with
      nonobstructive hypertrophic cardiomyopathy to exercise.
AB  - Stroke volume (SV), cardiac output (CO) and systolic blood pressure (SBP) were
      measured during maximal symptom-limited bicycle exercise testing in 13 young
      patients (age, 11-26 years) with nonobstructive hypertrophic cardiomyopathy
      (HCM). SV was measured by impedance plethysmocardiography; %SVend, %COend, and
      %SBPend represent the ratio of the value at termination of the exercise to the
      respective value at rest. In all patients of HCM-I (the Cardiac Event Group, 3
      patients) and 3 of HCM-II (the Non-Cardiac Event Group, 10 patients), the %SVend
      was less than 100%. The %SVend of HCM-I was significantly lower than the
      respective values of the HCM-II and Control groups. The %COend values of the HCM
      I and HCM-II groups were each significantly lower than that of the Control. The
      %SBPend values of the HCM-I and HCM-II groups were each significantly lower than
      that of the Control. Among the HCM patients, the %SVend value was positively
      correlated with the %SBPend value. The patients who had more severe HCM had
      poorer exercise-induced increases in SV and SBP. These results suggest that
      sudden cardiac death in young HCM patients is associated with inhibition of the
      increase in SV upon exercise.

PMID- 11316128
TI  - Effect of cilnidipine on left ventricular diastolic function in hypertensive
      patients as assessed by pulsed Doppler echocardiography and pulsed tissue Doppler
      imaging.
AB  - The purpose of the present study was to examine the mechanisms of improvement in
      left ventricular (LV) diastolic function in hypertensive patients treated with
      cilnidipine, a new and unique calcium antagonist that has both L-type and N-type
      voltage-dependent calcium channel blocking actions, using pulsed Doppler
      echocardiography and pulsed tissue Doppler imaging. The study comprised 35
      untreated patients with essential hypertension (19 men and 16 women; mean age
      65+/-10 years). The peak early diastolic and atrial systolic transmitral flow
      velocities (E and A, respectively) and their ratio (E/A), and the peak early
      diastolic and atrial systolic motion velocities (Ew and Aw, respectively) of the
      LV posterior wall and their ratio (Ew/Aw) were determined in all patients before
      and after 1, 3 and 6 months on cilnidipine (10 mg/day). One month: Systolic and
      diastolic blood pressures were significantly decreased. E and E/A were
      significantly increased, whereas there were no significant changes in Ew and
      Ew/Aw. Three months: Ew and Ew/Aw were significantly increased compared to those
      before and 1 month after cilnidipine. Six months: E and E/A were significantly
      increased compared with before and 3 months after cilnidipine, and Ew and Ew/Aw
      were significantly increased compared with before cilnidipine. Moreover, the LV
      mass index was significantly decreased compared to that before cilnidipine. In
      summary, changes in LV diastolic performance in patients with essential
      hypertension following cilnidipine treatment were biphasic with an initial
      increase in early diastolic transmitral flow velocity and a later increase in
      early diastolic LV wall motion velocity. The initial and later changes can be
      related to an acute change in afterload and a later improvement in LV relaxation.

PMID- 11316129
TI  - Potentially protective effects of the Ser447-Ter mutation of the lipoprotein
      lipase gene against the development of coronary artery disease in Japanese
      subjects via a beneficial lipid profile.
AB  - Several DNA variants at the lipoprotein lipase (LPL) gene locus have been found
      to be associated with the plasma lipid levels and the prevalence of coronary
      artery disease (CAD). In particular, the Ser447-termination (Ter) mutation at the
      exon 9 of the LPL gene has the potential to elevate the plasma high-density
      lipoprotein (HDL) levels, but it remains unknown in the Japanese population. The
      present study investigated 93 CAD patients and 96 age- and sex-matched healthy
      controls. The Ser447-Ter mutation was determined by polymerase chain reaction
      restriction fragment length polymorphism method. The allelic frequency of the
      Ser447-Ter mutation was 0.103 in all subjects. The Ser447-Ter (GG and CG) group
      was associated with significantly higher levels of plasma HDL-cholesterol
      (p<0.001) and lower levels of plasma triglyceride than the CC group (p<0.02). The
      peak particle size of low-density lipoprotein (LDL) was significantly larger in
      the Ser447-Ter (GG and CG) group than in CC group (p<0.05). The frequency of the
      Ser447-Ter genotype in GG and CG was significantly lower in CAD than in the
      controls (11.9% vs 26%, odds ratio = 0.38; 95% confidence interval, 0.18-0.81;
      p<0.02). These results suggest that the Ser447-Ter mutation of the LPL gene is
      associated with high plasma HDL-cholesterol levels, low plasma triglyceride
      levels and a larger LDL particle size. This mutation may have a protective effect
      against the development of CAD via its favorable lipoprotein profile.

PMID- 11316130
TI  - Surgical treatment of primary cardiac tumors: 28 years' experience in Kanazawa
      University Hospital.
AB  - To examine the clinical features of primary cardiac tumors, 34 patients who
      underwent surgical treatment from 1973 to 2000 at the Kanazawa University
      Hospital were analyzed and the literature was reviewed. The 34 patients were
      divided into 3 categories: (i) myxomas; (ii) benign non-myxomas; and (iii)
      malignant tumors. Twenty-three patients (70%) were diagnosed with myxomas,
      including 22 left atrial myxomas and 1 right atrial myxoma. Seven patients (18%)
      were diagnosed with benign non-myxoma tumors, including 3 hemangiomas, 1 fibroma,
      1 rhabdomyoma, 1 pheochromocytoma, and 1 lipoma. Four patients (12%) were
      diagnosed with malignant tumors, including 2 angiosarcomas, 1 rhabdomyosarcoma,
      and 1 malignant fibrous histiocytoma. Among the myxoma patients, in-hospital
      mortality was 9% (2/23), late mortality was 10% (2/21), and no recurrent myxomas
      have been identified. Among benign non-myxoma patients there were no
      perioperative deaths; however, 1 patient died 11 years after surgery, with no
      linked cause. No recurrent tumors have been identified. Among malignant tumor
      patients, 1 patient died the day following surgery and the rest died within 14
      months. Early and late results of surgery were acceptable for those patients with
      benign tumors, while the prognosis for patients with malignant tumors was very
      poor.

PMID- 11316131
TI  - Elevated parasympathetic nerve tone in isoproterenol-induced neurally mediated
      syncope during head-up tilt testing.
AB  - To clarify the autonomic nerve mechanisms whereby isoproterenol induces vasovagal
      reaction, 32 patients with recurrent syncopal episodes of unknown origin
      underwent head-up tilt testing. Syncope was induced in 11 patients by a control
      tilt (control/+ group). The remaining 21 patients (control/- group) underwent the
      procedure during isoproterenol infusion. Syncope was induced in 13
      (isoproterenol/+ group), but not in the remaining 8 patients (isoproterenol/-
      group). High-frequency component (HF) and low-frequency component (LF)/HF, which
      are indices of heart rate variability, were assessed for 2-min intervals at
      baseline (T1) during the initial phase (T2) and at the end (T3) of tilting in
      each test. The ratios of HF and LF/HF at T2/T1 and T3/T2 were calculated. The HF
      value at T3 in the control/+ group was greater than that in the control/- group
      (1.47+/-0.91 vs 0.75+/-0.34; p<0.05). The HF value at T3 in the isoproterenol/+
      group was significantly greater than those in the isoproterenol/- group (1.19+/
      1.04 vs 0.43+/-0.23; p<0.05). The HF value at T2 in the isoproterenol/+ tended to
      be greater than in the isoproterenol/- group (1.30+/-0.85 vs 0.66+/-0.53;
      p=0.07). The ratio of HF for T2/T1 in isoproterenol/+ was greater than in the
      other groups (2.04+/-1.26 in isoproterenol/+ vs 0.58+/-0.39 in control/-, 0.47+/
      0.18 in control/+ and 0.71+/-0.45 in isoproterenol/-; p=0.0001), whereas that of
      HF for T3/T2 in the control/+ group was greater than in the other groups (1.48+/
      0.62 in control/+ vs 0.97+/-0.33 in control/-; p<0.05, 0.79+/-0.35 in
      isoproterenol/- and 0.88+/-0.37 in isoproterenol/+; p<0.01). No difference was
      observed in either LF/HF or the ratio of LF/HF among the groups. The early and
      persistent increase in parasympathetic nerve tone provoked by isoproterenol plays
      an important role in enhancing the vasovagal reaction during head-up tilt
      testing.

PMID- 11316132
TI  - Systolic dysfunction and blood pressure responses to supine exercise in patients
      with hypertrophic cardiomyopathy.
AB  - Left ventricular function and blood pressure responses were evaluated in 56
      patients with non-obstructive hypertrophic cardiomyopathy (HCM) and 12 control
      subjects by using a radionuclide ventricular function monitor during supine
      ergometer exercise. Patients with HCM were divided into 2 groups: (i) group A had
      no decrease in ejection fraction (EF) during exercise; and (ii) group B had a
      decrease in EF during exercise. During exercise, the change in end-diastolic
      volume did not differ between the 3 groups. In contrast, the change in end
      systolic volume differed between the 3 groups (p<0.0001). The change in systolic
      blood pressure (SBP) also differed significantly between the 3 groups. The change
      in SBP in group B was smaller than that in the control group and group A, and
      changes in the EF and changes in the SBP between rest and peak exercise showed a
      significant correlation (p<0.005). These results suggest that exercise-induced
      systolic dysfunction in patients with non-obstructive HCM may contribute to
      abnormal blood pressure response in those patients.

PMID- 11316133
TI  - Effects of cardioplegic arrest and reperfusion on rabbit cardiac ryanodine
      receptors.
AB  - Calcium overload is considered to be a primary contributor to ischemia
      reperfusion injury. Cardiac sarcoplasmic reticulum (SR), the main regulator of
      intracellular Ca2+ concentration under normal conditions, is a target for
      ischemic myocardial injury. The ryanodine receptor (RyR) is the SR Ca2+ release
      channel. Previous reports have shown that a reduction in RyR activity during
      global myocardial ischemia correlates with concomitant myocardial dysfunction.
      Crystalloid cardioplegia, a technique for myocardial protection during heart
      operations, reduces Ca2+ accumulation during global ischemia. Hence, the effects
      of cardioplegia on RyR in isolated rabbit hearts was investigated. The study also
      compared [3H] ryanodine binding before ischemia (control group), after 30 min of
      ischemia (either global ischemia (GI group) or cardioplegic arrest (CA group)),
      and after 20 min of reperfusion. The GI group, but not the CA group, showed a
      significant reduction in the maximum number of binding sites (Bmax) for RyR
      compared with the control group (Control vs GI group: after ischemia, 1.33+/-0.27
      vs 0.83+/-0.12 pmol/mg protein, p<0.05; after reperfusion, 1.33+/-0.27 vs 0.80+/
      0.08 pmol/mg protein; p<0.05). CA group: after ischemia, 1.22+/-0.20 pmol/mg
      protein; after reperfusion, 1.15+/-0.28 pmol/mg protein). The affinity (Kd)
      values for [3H] ryanodine binding were not different among the 3 groups at any
      point. The preservation of RyR numbers during cardioplegia correlated with the
      concomitant preservation of cardiac functions. The results indicate that number
      of functional RyR was much better preserved during cardioplegia than during
      global ischemia. It is postulated that cardioplegia-induced protection of cardiac
      RyR may result in the protection of SR function during ischemia-reperfusion.

PMID- 11316134
TI  - Inhomogeneity in the appearance of electrical remodeling during chronic rapid
      atrial pacing: evaluation of the dispersion of atrial effective refractoriness.
AB  - In the present study, the long-term process of progression of electrical
      remodeling at various atrial sites, which is not well understood, was compared
      while monitoring continuously the electrophysiologic parameters at multirecording
      sites in canine atria during continuous atrial burst pacing. A rapid pacing
      device was implanted in 5 dogs, and continuous atrial burst pacing (400
      beats/min) was delivered at the right atrial appendage (RAA). Four pairs of
      epicardial wire electrodes were sutured on (1) the RAA, (2) Bachmann's bundle
      (BB), (3) the right atrium close to the inferior vena cava (IVC), and (4) the
      left atrium (LA). The distal ends of those wires were exteriorized posteriorly
      and used for pacing and recording. The atrial effective refractory period (AERP),
      AERP dispersion (AERPd), atrial conduction time (CT) and inducibility of atrial
      fibrillation (AF) were evaluated during burst pacing for 14 days and during the
      subsequent 7 days' recovery. The AERP at the LA pacing site was shorter than that
      at the other sites on day 0. The AERP shortening was greater in the RAA and LA
      sites than in the BB and IVC sites. The AERPd increased during pacing and reached
      the maximum level on day 3, and then decreased during the recovery phase.
      Prolongation of CT tended to be longer between the RAAand IVC sites than that
      between the other sites. The incidence of AF induction became higher in
      accordance with the time course of the rapid pacing phase. There was another peak
      of AF induction on days 7-10. In a canine chronic rapid atrial stimulation model,
      the progression of electrical remodeling (ie, the shortening of the AERP and the
      prolongation of the CT) was not homogeneous in both atria, the AERPd showed a
      temporal increase between days 3 and 7 and matched the increase in AF
      inducibility at the LA pacing site, the increase in the AERPd was mainly caused
      by more rapid AERP shortening at the RAA or LA sites, and the LA site always
      showed a shorter AERP than the other atrial sites in the control state and during
      the rapid pacing phase, whereas AF inducibility was higher at the LA site than
      the other sites.

PMID- 11316135
TI  - Echocardiographical demonstration of a progressively expanding left ventricular
      aneurysm preceded by endomyocardial tearing.
AB  - A 70-year-old woman with acute myocardial infarction (AMI) had a narrow necked
      left ventricular (LV) aneurysm and pericardial effusion. Although there had been
      no obvious sign of pseudoaneurysm at the first operation on the 13th day after
      onset, LV volume increased so dramatically that dyspnea on mild exertion was
      induced only 2 months after the onset of AMI. She underwent Dor's operation for
      the expanded LV aneurysm. The histological findings of the resected tissue, which
      were fibrotic epicardial lesion with small myocyte islands, indicated a true
      aneurysm. The ultrasound manifestation of a narrow necked aneurysm with abrupt
      thinning of the myocardium at the hinge point may be a valuable predictor of free
      wall rupture in the early phase and severely progressive LV remodeling in the
      late phase. Such aneurysms need to be considered as high risk.

PMID- 11316136
TI  - Repeated postpericardiotomy syndrome following a temporary transvenous pacemaker
      insertion, a permanent transvenous pacemaker insertion and surgical
      pericardiotomy.
AB  - The postpericardiotomy syndrome is a well-known complication of opening and
      manipulating the pericardium. The occurrence of this syndrome following
      transvenous pacemaker insertion is very rare, and only 5 cases have been reported
      to date. The present patient repeated this syndrome 3 times in a short period
      following 3 different interventional techniques: a temporary transvenous
      pacemaker, a permanent transvenous pacemaker and surgical pericardiotomy.

PMID- 11316137
TI  - Recurrence of myocarditis presenting as pacing and sensing failure after
      implantation of a permanent pacemaker at first onset.
AB  - A 31-year-old woman was admitted to hospital with loss of consciousness and
      generalized convulsions. Electrocardiography (ECG) showed complete
      atrioventricular block (AV block) with a pulse rate of 30 beats/min.
      Endomyocardial biopsy from the right ventricle showed massive necrosis and
      degeneration of myocardial cells with extensive infiltration of lymphocytes into
      the interstitial space. These pathological findings suggested fulminant
      myocarditis. Following glucocorticoid therapy, the patient became asymptomatic,
      but the AV block did not resolve completely and a bifocal pacemaker was
      implanted. However, similar symptoms recurred 7 years later. An ECG showed pacing
      and sensing failure linked to an increase in the pacing threshold and a decrease
      in the sensing threshold. Endomyocardial biopsy from the right ventricle again
      showed interstitial infiltration with lymphocytes and eosinophils. After
      glucocorticoid therapy, she became asymptomatic once more, and the improvement in
      the pacing and sensing failure, and cardiomegaly, was satisfactory. This patient
      represents a very rare case of recurrence of acute myocarditis without
      progression, as much as 7 years after its first occurrence. Glucocorticoid
      therapy was still effective in treating the recurrent myocarditis presenting with
      pacing and sensing failure.

PMID- 11316138
TI  - Emotional stress-induced 'ampulla cardiomyopathy': discrepancy between the
      metabolic and sympathetic innervation imaging performed during the recovery
      course.
AB  - Four patients had the clinical features of 'ampulla cardiomyopathy', consisting
      of acute-onset transient left ventricular apical akinesis with basal
      normokinesis, normal coronary angiogram, ST-segment elevation and subsequent
      giant T wave inversion, which mimicked acute coronary syndrome, the onset of
      which occurred shortly after extreme mental stress. Myocardial necrosis was
      minimal, although 2 patients showed elevated serum catecholamine levels in the
      acute phase. Each patient underwent serial cardiac radionuclide single-photon
      emission computed tomography of myocardial functional sympathetic innervation,
      fatty acid metabolism and perfusion using I-123-metaiodobenzyl-guanidine (MIBG),
      I-123-beta-metyl-iodophenyl pentadecanoic acid (BMIPP) and thallium-201 (201Tl),
      respectively. In the acute phase, MIBG and BMIPP imaging showed an uptake defect
      in the apical region, whereas 201Tl uptake was mildly decreased. When assessed
      semi-quantitatively, the MIBG images had higher defect scores from the acute
      phase throughout the year of observation compared with BMIPP, and 201Tl. These
      observations suggest that the primary cause of ampulla cardiomyopathy is related
      to a disturbance of the cardiac sympathetic innervation.

PMID- 11316139
TI  - Helicobacter pylori vacA, iceA, and cagA status and pattern of gastritis in
      patients with malignant and benign gastroduodenal disease.
AB  - OBJECTIVE: Both bacterial virulence factors and the pattern of Helicobacter
      pylori (H. pylori) gastritis may contribute to the development of clinically
      relevant gastroduodenal disease. The aim of our study was to investigate the
      frequency of H. pylori vacA alleles, iceA, and cagA, and the pattern of gastritis
      in patients with gastric cancer (GC), gastric lymphoma (MALT), duodenal ulcer
      (DU), and functional dyspepsia (FD). METHODS: H. pylori was cultured from 141
      patients (34 GC, 26 MALT, 49 DU, 32 FD). Allelic variants of vacA and iceA, and
      cagA were identified by polymerase chain reaction. Antrum and corpus biopsies
      were obtained for assessment of gastritis according to the updated Sydney System.
      RESULTS: The vacA sl,ml genotype was more frequently detected in H. pylori from
      GC patients (70.6%) than from MALT, DU, and FD patients (p < 0.05). The frequency
      of iceA1 and cagA did not differ among the groups. The proportion of patients
      with severe gastritis in the corpus was significantly higher in patients with GC
      and MALT compared with patients with DU (p < 0.001). CONCLUSIONS: In a German
      patient population, only the vacA s1,m1 genotype of H. pylori is associated with
      GC, and therefore may be useful to identify infected patients being at an
      increased risk for GC.

PMID- 11316140
TI  - Helicobacter pylori infection and serum ferritin: A population-based study among
      1806 adults in Germany.
AB  - OBJECTIVE: Helicobacter pylori may possibly affect the iron metabolism by occult
      bleeding, impaired absorption of non-hem iron, and by scavenging hem iron or
      ferritin, as some studies have suggested. The aim of this study was to analyze
      the association between H. pylori infection and serum ferritin, a marker of the
      body iron stores. In this analysis, we paid particular attention to the role of
      dietary iron intake and CagA, an established virulence factor of the agent.
      METHODS: The analysis is based on a cross-sectional national health and nutrition
      survey among healthy people in Germany conducted in 1987/1988. The examination
      included a detailed questionnaire on medical history and lifestyle factors, a 7
      day food record, and blood samples. Infection with H. pylori was measured
      serologically by ELISA and Westernblot. RESULTS: In total, 39.2% of 1806 persons
      aged 18 to 89 yr included in the study were H. pylori positive, of whom 57.6% had
      an infection with a CagA-positive H. pylori strain. Age- and sex-adjusted
      geometric mean of ferritin was 54.5 microg/dl among H. pylori-infected compared
      with 63.8 microg/dl among uninfected persons. A multiple linear regression model
      with log-transformed serum ferritin concentration as dependent variable and H.
      pylori infection and several potential confounding factors as independent
      variable was fitted. In this model, H. pylori infection was associated with a
      17.0% decrease of the serum ferritin concentration (95% CI = 9.8-23.6). The
      association between H. pylori infection and serum ferritin levels did not vary by
      gender, age, and iron intake, and it was similar for CagA-positive and CagA
      negative H. pylori infections. CONCLUSIONS: The decreased serum ferritin
      concentration among subjects infected with H. pylori might be induced by the
      uptake of ferritin in the stomach by H. pylori. Possible health implications of
      H. pylori-induced low ferritin levels warrant further investigation.

PMID- 11316141
TI  - Reduced incidence of gastroduodenal ulcers with celecoxib, a novel cyclooxygenase
      2 inhibitor, compared to naproxen in patients with arthritis.
AB  - OBJECTIVE: Nonsteroidal anti-inflammatory drugs (NSAIDs) block prostaglandin
      production by inhibiting cyclooxygenase (COX); they are believed to cause
      gastroduodenal damage by inhibiting the COX-1 isoform and to have analgesic and
      anti-inflammatory effects by inhibiting the COX-2 isoform. As compared to
      conventional NSAIDs, celecoxib, a COX-2 specific inhibitor, has been shown in
      previous single posttreatment endoscopy studies to be associated with lower
      gastroduodenal ulcer rates. In response to concerns that such studies may under
      represent ulceration rates, the present serial endoscopy study was designed to
      compare cumulative gastroduodenal ulcer rates associated with the use of
      celecoxib to those of naproxen, a conventional NSAID. METHODS: In this double
      blind, parallel-group, multicenter study, 537 patients with osteoarthritis (OA)
      or rheumatoid arthritis (RA) were randomized to treatment with celecoxib 200 mg
      b.i.d. (n = 270) or naproxen 500 mg b.i.d. (n = 267) for 12 wk. Gastroduodenal
      damage was determined from esophagogastroduodenoscopy after 4, 8, and 12 wk of
      therapy. Arthritis efficacy was evaluated with Patient's and Physician's Global
      Assessments. RESULTS: Gastroduodenal ulcer rates after celecoxib and naproxen
      treatment were 4% versus 19% in the 0-4 wk interval (p < 0.001), 2% versus 14% in
      the 4-8 wk interval (p < 0.001), and 2% versus 10% in the 8-12 wk interval (p <
      0.001), respectively. After 12 wk of treatment, the cumulative incidence of
      gastroduodenal ulcers was 9% with celecoxib and 41% with naproxen. In the
      celecoxib group, gastroduodenal ulcers were significantly associated with
      Helicobacter pylori status (p < 0.05), concurrent aspirin usage (p = 0.001), and
      a history of ulcer (p = 0.010), but not with disease type (OA/RA), age, gender,
      other relevant medical histories, or concurrent corticosteroid or disease
      modifying antirheumatic drugs usage (p > 0.05). Celecoxib produced a
      significantly lower incidence rate of both gastric (p < 0.001) and duodenal (p <
      0.030) ulcers. The two agents produced similar improvements in Patient's and
      Physician's Global Assessments of arthritis efficacy. The incidence of adverse
      events and withdrawal rates did not differ significantly between treatments.
      CONCLUSIONS: As compared to naproxen (500 mg b.i.d.), use of celecoxib (200 mg
      b.i.d.), a COX-2 specific agent, at the recommended RA dose and twice the most
      frequently prescribed OA dose, was associated with lower rates of gastric,
      duodenal, and gastroduodenal ulcers but had comparable efficacy, in patients with
      OA and RA.

PMID- 11316142
TI  - Intragastric acidification reduces the occurrence of false-negative urea breath
      test results in patients taking a proton pump inhibitor.
AB  - OBJECTIVE: The aim of this study was to investigate whether reducing intragastric
      pH, at the time of urea ingestion, decreases the likelihood of false-negative
      (FN) urea breath test (UBT) results in patients taking a proton pump inhibitor
      (PPI). METHODS: Patients with active Helicobacter pylori infection underwent a
      baseline 14C-UBT (UBT-1) followed by treatment with lansoprazole 30 mg/day for 14
      to 16 days. On day 13, patients returned for a repeat standard UBT (UBT-2).
      Between days 14 to 16, patients underwent a modified UBT (UBT-3), which included
      consuming 200 ml of 0.1 N citrate solution 30 min before and at the time of 14C
      urea administration. Breath samples were collected 10 and 15 min after 14C-urea
      ingestion. Mean 14CO2 excretion and the number of FN and equivocal UBT results
      were compared for the three UBTs. RESULTS: A total of 20 patients completed the
      study. Lansoprazole caused a significant decrease in mean breath 14CO2 excretion
      (disintegrations per minute) between UBT-1 (2.96 +/- 0.23) and UBT-2 (2.08 +/-
      0.52, p < 0.05). Lansoprazole caused six (30%) FN and eight (40%) equivocal UBT-2
      results. Mean breath 14CO2 excretion for UBT-3 (677 +/- 514) was greater than for
      UBT-2 (234 +/- 327, p = 0.001). UBT-3 caused only two (10%) FN and three (15%)
      equivocal results. The 15-min breath sample caused fewer FN and equivocal results
      than the 10-min sample for both UBT-2 and UBT-3. CONCLUSIONS: Giving citrate
      before and at the time of 14C-urea administration increases mean breath 14CO2
      excretion and decreases FN and equivocal UBT results in patients taking a PPI.
      These observations suggest that it may be possible to design a UBT protocol that
      will remain accurate in the face of PPI therapy.

PMID- 11316143
TI  - Psychological distress is linked to gastrointestinal symptoms in diabetes
      mellitus.
AB  - OBJECTIVE: Gastrointestinal (GI) symptoms are common in patients with long
      standing diabetes mellitus, but the pathogenesis is controversial. We aimed to
      determine if GI symptoms are linked to psychological distress in diabetes.
      METHODS: A consecutive sample of outpatients with diabetes mellitus (n = 209) and
      a random sample of community diabetics (n = 892) completed a validated
      questionnaire measuring GI symptoms, the Hospital Anxiety and Depression (HAD)
      Scale for anxiety and depression, and the Eysenck short neuroticism scale.
      RESULTS: Overall, 42% reported one or more GI symptoms: bloating, abdominal pain,
      loose stools, and urgency were most common. The mean HAD and neuroticism scores
      were significantly higher for most GI symptoms (11 of 14, all p < 0.05), and a
      dose-response relationship was observed. GI symptoms were, in general,
      approximately twice as frequent in cases with anxiety or depression (HAD > or =
      11). Anxiety, depression, and neuroticism were each independently associated with
      the number of GI symptoms, adjusting for age, gender, duration and type of
      diabetes, and self-reported glycemic control. CONCLUSIONS: Increased levels of
      state anxiety and depression and neuroticism are associated with upper and lower
      GI symptoms in diabetes mellitus. It is uncertain whether psychological distress
      is causally linked to symptoms, or whether GI symptoms per se increase levels of
      anxiety and depression.

PMID- 11316144
TI  - Helicobacter pylori infection is not associated with diabetes mellitus, nor with
      upper gastrointestinal symptoms in diabetes mellitus.
AB  - OBJECTIVE: The association between Helicobacter pylori (H. pylori) infection and
      diabetes mellitus is controversial. We aimed to determine the prevalence of H.
      pylori infection in patients with diabetes and nondiabetic controls, and assess
      whether H. pylori infection was associated with upper gastrointestinal (GI)
      symptoms in diabetes mellitus. METHODS: A total of 429 patients with type 1 (n =
      49) or type 2 (n = 380) diabetes mellitus (48.6% women, mean age 60.7 yr) and 170
      nondiabetic controls (34.7% women, mean age 60.4 yr) were evaluated. All subjects
      completed a validated questionnaire (the Diabetes Bowel Symptom Questionnaire) to
      determine upper GI symptoms, and a blood sample was tested for H. pylori
      infection using a validated ELISA kit (sensitivity 96%, specificity 94%).
      RESULTS: Seroprevalence of H. pylori was 33% and 32%, respectively, in patients
      with diabetes and controls (NS). In both groups, the seroprevalence was
      significantly higher in men than in women; 39% vs 25% (p = 0.002) in diabetic
      patients, and 40% vs 20% (p = 0.01) in controls. Patients with diabetes had a
      significantly higher prevalence of early satiety (OR = 2.30), fullness (OR =
      3.15), and bloating (OR = 1.50) compared with controls. Upper GI symptoms were
      present in 49% of H. pylori-positive and 53% of H. pylori-negative patients with
      diabetes (OR = 0.87, 95% CI 0.58-1.31, p = 0.56). H. pylori infection was also
      not associated with any of the individual upper GI symptoms before or after
      adjustment for potential confounding factors. However, patient age and female
      gender were identified as independent risk factors for upper GI symptoms. Smoking
      was a risk factor for bloating and early satiety. CONCLUSIONS: H. pylori
      infection appears not to be associated with diabetes mellitus or upper GI
      symptoms in diabetes mellitus.

PMID- 11316145
TI  - Reproducibility of gastric barostat studies in healthy controls and in dyspeptic
      patients.
AB  - OBJECTIVES: Gastric barostat studies are increasingly being performed, but their
      reproducibility and the most suitable study protocol have not been determined.
      The aim of this study was to verify the reproducibility of gastric sensitivity
      and accommodation testing in healthy and in dyspeptic subjects, and to compare
      stepwise and double random staircase distensions. METHODS: A total of 13
      dyspeptic patients and 25 healthy control subjects underwent two successive
      studies. Sensory thresholds were assessed on a same-day/different-days protocol,
      using a stepwise (11/14 healthy subjects and 11/13 patients) or a double random
      staircase inflation (11/21 healthy subjects). In 10 healthy subjects, both
      methods were compared. Gastric accommodation was measured on different days in 13
      patients and nine healthy subjects. Data (mean +/- SEM) were compared using the
      paired t test, and individual variability was expressed as the percent
      coefficient of variation. RESULTS: In healthy subjects, the thresholds for first
      perception and for discomfort were highly reproducible (p > 0.05) and the
      pressure thresholds showed a lower degree of variability than the volumes.
      Pressure thresholds quantified by stepwise showed lower variability than double
      random staircase inflation. In the patients, the sensory thresholds were
      unchanged between the sessions on the same and on different days (p > 0.05).
      Gastric accommodation also showed excellent reproducibility for both dyspeptic
      patients and healthy control subjects (p > 0.05). CONCLUSIONS: Both in dyspeptic
      patients and in healthy control subjects, gastric sensitivity and accommodation
      quantified by isobaric distensions show excellent reproducibility. Pressure and
      volume thresholds both are well reproducible, but the former shows less
      variability. Finally, the simplest stepwise protocol is better than the double
      random staircase to assess the gastric sensitivity to distension.

PMID- 11316146
TI  - Diagnostic accuracy of simpson atherectomy catheter biopsy in detecting
      pancreaticobiliary malignancy.
AB  - OBJECTIVE: Impressive advances have been made in imaging the biliary tree by
      various modalities in the last few decades. However, the histological diagnosis
      of stenosing lesions in the biliary ductal system has remained difficult and
      unreliable. Application of Simpson atherectomy catheter biopsy in obtaining
      accurate histological diagnosis of bile duct lesions appears promising. The
      purpose of our study was to determine the clinical accuracy of the Simpson
      atherectomy catheter biopsy in the evaluation of bile duct strictures. METHODS: A
      retrospective study of medical records of patients who underwent bile duct biopsy
      by atherectomy catheter was conducted between 1991 and 1999. During this period,
      53 patients underwent 56 endoluminal bile duct biopsies with an atherectomy
      catheter as part of an obstructive jaundice workup. Histological diagnosis on
      biopsy was confirmed by subsequent surgical biopsy and/or clinical follow-up.
      RESULTS: Fifty-four (96%) bile duct biopsies were technically successful in terms
      of yielding a histological diagnosis. Thirty-one of the 56 (55%) biopsy specimens
      were positive for malignancy (27 adenocarcinoma, two islet cell-carcinoids, one
      small cell carcinoma, and one malignant lymphoma). Four (7%) were read by the
      pathologist as highly suspicious for malignancy, and 19 (34%) specimens were
      considered negative for malignancy. Sensitivity of atherectomy catheter
      endoluminal biliary biopsy in this study was 97% with a specificity of 100%. In
      addition, the positive predictive and negative predictive values of this modality
      were 100% and 93%, respectively. CONCLUSIONS: Endoluminal bile duct biopsy by
      Simpson atherectomy catheter appears to be a highly sensitive and specific method
      for establishing histological diagnosis of stenosing lesions in the biliary
      ductal system.

PMID- 11316147
TI  - Balloon dilation compared to stenting of dominant strictures in primary
      sclerosing cholangitis.
AB  - OBJECTIVE: In some patients with primary sclerosing cholangitis (PSC), a
      localized, high-grade (dominant) stricture may be the principal cause of symptoms
      and hyperbilirubinemia. The aim of this retrospective study was to compare the
      beneficial effects and risk of balloon dilation alone versus dilation followed by
      stenting in PSC patients with dominant strictures. METHODS: Charts from a group
      of 1009 patients with PSC seen over 10 yr were reviewed to identify those
      patients who had undergone endoscopic or percutaneous therapeutic intervention.
      Procedural and clinical data were recorded. RESULTS: A total of 71 PSC patients,
      median age of 49 yr (range 18-78 yr) were identified. Thirty-four patients were
      treated with endoscopic balloon dilation alone, and 37 patients were treated with
      balloon dilation plus stent placement. Stents were placed percutaneously (n =
      19), endoscopically (n = 14), or using both interventions (n = 4). Both groups
      were comparable at baseline with regards to age, symptoms, and bilirubin level.
      The median duration of follow-up after intervention was similar in both groups.
      The number of intervention-related complications (30 vs 6, p = 0.001) as well as
      the incidence of acute cholangitis (p = 0.004) were more common in the stent
      group compared to the balloon dilation group. There were more complications
      related to percutaneous stent placement than endoscopic placement (23 vs 7. p =
      0.001). There was no significant difference between the two groups with regards
      to improving cholestasis. CONCLUSIONS: There was no additional obvious benefit
      from stenting after balloon dilation in the treatment of dominant strictures in
      PSC patients. Stenting was associated with more complications, and its role after
      dilation should be assessed in a randomized trial rather than being accepted as
      routinely indicated in this setting.

PMID- 11316148
TI  - Nonsurgical management of ruptured pseudoaneurysm in patients with hepatobiliary
      pancreatic diseases.
AB  - OBJECTIVE: Rupture of a pseudoaneurysm is an unusual complication after surgical
      and interventional treatments in patients with hepatobiliary pancreatic diseases.
      However, it occurs abruptly and often results in a lethal outcome. The aim of
      this study was to retrospectively analyze our experiences of cases of rupture of
      pseudoaneurysms for providing appropriate therapeutic planning. METHODS: Between
      1985 and 1998, we observed ruptures of pseudoaneurysms in 14 of 910 patients with
      hepatobiliary pancreatic diseases--six after pancreaticoduodenectomy, three after
      hepatic resection, two after hepatopancreaticoduodenectomy, two after
      percutaneous transhepatic biliary drainage, and one after gastrojejunostomy.
      Thirteen of the 14 patients underwent emergency angiography and transcatheter
      arterial embolization (TAE) or infusion therapies, and one of the 13 patients
      underwent surgical hemostasis because of incomplete hemostasis with TAE. The
      other patient, who did not undergo emergency angiography, had surgical hemostasis
      initially. RESULTS: TAE achieved hemostasis in 11 of 13 patients (85%), but only
      incomplete hemostasis in the remaining two patients. Of these two patients, one
      underwent laparotomy, but died of multiple organ failure (MOF) at 6 days after
      surgical hemostasis. The other died at 1 day after emergency angiography. Ten of
      11 patients who obtained complete hemostasis by means of TAE could later be
      discharged, but one patient died of liver failure, and/or MOF. One patient who
      underwent laparotomy initially without angiography died of MOF at 43 days after
      the operation. The onset of rupture of a pseudoaneurysm was a mean of 35.4 days
      (range 12-76) after surgical or interventional procedures. The warning prodromal
      symptoms were upper abdominal oppression, nausea, and backache before the rupture
      of pseudoaneurysms. Fever, leukocytosis. hyperbilirubinemia, anastomotic leak,
      and intraabdominal abscess were frequent persistent signs in these patients.
      CONCLUSIONS: If the warning prodromal symptoms appear in patients along with
      these persistent signs, the impending rupture of pseudoaneurysms should be
      suspected. Thereafter, a diagnostic angiography should be performed immediately
      to enable early diagnosis and embolization therapy for rupture of pseudoaneurysms
      when hemorrhagic episodes appear in these patients. Early detection and immediate
      embolization might bring about a favorable outcome in patients with hepatobiliary
      pancreatic diseases who encounter rupture of pseudoaneurysms after surgical and
      interventional treatments.

PMID- 11316149
TI  - The irritable bowel syndrome and psychiatric disorders in the community: is there
      a link?
AB  - OBJECTIVE: Psychiatric morbidity is high among patients who present to referral
      centers with irritable bowel syndrome (IBS). However, few studies have
      investigated the relationship between psychiatric disturbance and IBS in
      community samples. We hypothesized that psychiatric disorders are linked to IBS
      in the general community, but this is influenced by the criteria used to
      establish a diagnosis of IBS. METHODS: The data were collected from a birth
      cohort born in Dunedin (New Zealand) between April 1972 and March 1973. This
      cohort consisted of 1037 members (52% male), who were assessed at ages 3, 5, 7,
      9, 11, 13, 15, 18, 21, and 26 yr. GI symptoms were recorded at age 26 yr, using
      an abbreviated version of the Bowel Symptom Questionnaire; psychiatric history
      was obtained at ages 18 and 21 yr, using a modified version of the Diagnostic
      Interview Schedule. RESULTS: The prevalence of IBS was 12.7% according to the
      Manning criteria and 4.3% according to the Rome II criteria. The IBS was not
      significantly related to a diagnostic history for psychiatric illness overall,
      nor to a history of anxiety disorders, depressive disorders, and substance
      dependence. These results were independent of the IBS criteria used; there was no
      association between psychiatric history and IBS when IBS was defined according to
      the Manning criteria (p = 0.11 to 0.98) or the Rome criteria (p = 0.18 to 0.92):
      Rome and Manning criteria subjects did not significantly differ from each other
      in terms of psychiatric history (p = 0.16 to 0.89). CONCLUSION: In a cohort of
      young adults with IBS from New Zealand, IBS appears to not be related to
      psychiatric disorders.

PMID- 11316150
TI  - Successful and sustained treatment of chronic radiation proctitis with
      antioxidant vitamins E and C.
AB  - OBJECTIVE: Chronic radiation proctitis, a common sequelae of pelvic radiation, is
      characterized by obliteration of the submucosal vasculature with subsequent
      ischemia and reperfusion injury. Oxidative stress is thought to be a major
      mechanism in radiation proctitis. Therefore, antioxidants (vitamins E and C) may
      be beneficial. METHODS: Twenty consecutive symptomatic outpatients with
      endoscopically documented radiation proctitis seen in a single gastroenterology
      clinic were given a combination of vitamin E (400 IU tid) and vitamin C (500 mg
      tid). Previous radiation therapy was given for prostatic (n = 10) or
      gynecological (n = 10) malignancies. These patients presented with one or more of
      the following symptoms: rectal bleeding, rectal pain, diarrhea, or fecal urgency.
      Using a questionnaire, these symptoms were rated by the patients in terms of
      their severity (grade 0-4) and frequency (grade 0-4) before and after treatment
      with vitamins E and C. A symptom index was calculated by the addition of the
      severity and frequency scores (8 = most symptomatic). The lifestyle impact of the
      symptoms was also assessed by questionnaire grading from 0 (no effect on daily
      activity) to 4 (afraid to leave home). Among these 20 patients, 10 patients who
      received vitamins E and C for 1 yr were assessed again to determine whether their
      initial responses were sustained. RESULTS: There was a significant (p < 0.05;
      Wilcoxon rank) improvement in the symptom index (before treatment vs after
      treatment with vitamins E and C) for bleeding (median score: 4 vs 0), diarrhea
      (median score: 5 vs 0), and urgency (median score: 6 vs 3). Patients with rectal
      pain did not improve significantly. Bleeding resolved in four of 11 patients,
      diarrhea resolved in eight of 16 patients, fecal urgency resolved in three of 16
      patients, and rectal pain resolved in two of six patients. Lifestyle improved in
      13 patients, including seven patients who reported a return to normal. Two of the
      patients with no improvement in their daily symptoms also had radiation ileitis.
      All 10 patients who underwent a second follow-up interview reported sustained
      improvement in their symptoms 1 yr later. CONCLUSION: A substantial number of
      patients with radiation proctitis seem to benefit from antioxidant therapy. A
      double-blind placebo-controlled trial is needed to confirm this open-labeled
      pilot study.

PMID- 11316151
TI  - Neutrophil and eosinophil granule proteins as markers of response to local
      prednisolone treatment in distal ulcerative colitis and proctitis.
AB  - OBJECTIVE: The pathophysiological role of neutrophil and eosinophil granulocytes
      in relation to steroid enema treatment was studied in patients with distal
      ulcerative colitis and proctitis. METHODS: The rectal release of the neutrophil
      (myeloperoxidase, MPO), and eosinophil (eosinophilic cationic protein, ECP and
      eosinophil peroxidase, EPO) granule constituents were measured in 11 patients
      using intraluminal segmental perfusion of the rectum. The released amounts of
      MPO, ECP, and EPO in the perfusion fluids were determined by radioimmunoassays
      before and during prednisolone enema treatment and related to clinical,
      endoscopical, and histopathological data in addition to treatment outcome.
      RESULTS: Clinical activity and particularly endoscopic activity correlated well
      with intraluminal MPO concentrations both before and during treatment. At the end
      of the study, eight of 11 patients fulfilled predefined response criteria; all
      responding patients had significant decrease of MPO concentrations (p < 0.01).
      This decline of MPO concentration was seen after 7 days of treatment (p < 0.05)
      in the response group and often occurred before clinical improvement. There was a
      nonsignificant trend toward a decrease in the concentrations of ECP and EPO at
      the end of treatment in responders.

PMID- 11316152
TI  - Usefulness of colonoscopy with biopsy in the evaluation of patients with chronic
      diarrhea.
AB  - OBJECTIVE: Patients referred for chronic diarrhea frequently undergo endoscopic
      evaluation. There are limited data on the role for colonoscopy with biopsy and
      ileoscopy for patients with chronic diarrhea. METHODS: We reviewed the charts of
      228 patients with chronic diarrhea evaluated by colonoscopy between November 1995
      and March 1998. Chronic diarrhea was defined as loose, frequent bowel movements
      for a minimum of 4 wk. Patients were excluded if biopsies were not performed in
      normal colons, if they had undergone previous bowel surgery, a history of
      inflammatory bowel disease, HIV, or an inadequate colonoscopy. RESULTS: One
      hundred sixty-eight patients were included in the analysis, of whom 142 (85%) had
      ileoscopy. Colonoscopy and biopsy yielded a specific histological diagnosis in 52
      (31%) patients. These included Crohn's disease (9), ulcerative colitis (7),
      lymphocytic colitis (10), collagenous colitis (3), ischemic colitis (3),
      infectious colitis (6), and miscellaneous diseases (14). Ileoscopy yielded
      significant findings in 3% of patients (four with Crohn's disease and one with
      infection). CONCLUSIONS: Colonoscopy and biopsy is useful in the investigation of
      patients with chronic diarrhea yielding a histological diagnosis in 31% of
      patients without a previous diagnosis. Ileoscopy complemented colonoscopy
      findings in a minority of patients with chronic diarrhea and was essential for a
      diagnosis in only two patients.

PMID- 11316153
TI  - Macroamylasemia in patients with celiac disease.
AB  - OBJECTIVE: Macroamylasemia is considered to be rarely associated with celiac
      disease (CD). We have evaluated patients in whom macroamylasemia or elevated
      total amylase (TA) led to the diagnosis of CD. These cases served as a catalyst
      for examining the prevalence of elevated TA and macroamylase (MA) in patients
      with active CD. METHOD: Total amylase and MA measurements were performed in the
      sera of 124 celiac patients with positive antiendomysium and tissue
      transglutaminase tests, in 100 patients on gluten-free diet (GFD) with negative
      serology test results, and in the sera of 89 healthy controls. Macroamylasemia
      was measured by using the PEG precipitation method. RESULTS: Twenty-three newly
      diagnosed celiac patients had elevated serum amylase levels (>2 SD above the
      controls). The average TA and MA levels were significantly elevated in both
      celiac groups. The nonprecipitated amylase levels (pancreatic and salivary
      amylase fractions) were not different from those of the controls. Three controls
      (3.4%), 21 newly diagnosed celiac (16.8%), and seven patients on GFD (7%) had
      significantly elevated MA activity in their sera. CONCLUSIONS: A significant
      percentage of the newly diagnosed patients with CD have macroamylasemia. Serum MA
      remained elevated in some patients on strict GFD. In addition, in the presence of
      an elevated amylase or MA the possibility of CD should be considered.

PMID- 11316154
TI  - Occupational mortality from inflammatory bowel disease in the United States 1991
      1996.
AB  - OBJECTIVE: The occupational distribution of inflammatory bowel disease (IBD) may
      help to shed light on its yet unknown etiology. The U.S. vital statistics offer
      the opportunity to study cause of death by occupation and industry. METHODS: The
      numbers of deaths from Crohn's disease and ulcerative colitis were retrieved from
      the computerized 1991-1996 data files of the National Center for Health
      Statistics. Deaths were grouped by gender, ethnicity, disease type, occupation,
      and industry. Mortality by occupation and industry were expressed as proportional
      mortality ratio (PMR), adjusted for gender and ethnicity. RESULTS: Between 1991
      and 1996, 2399 subjects died from Crohn's disease and 2419 subjects died from
      ulcerative colitis. Significant correlations were found between the PMR values of
      ulcerative colitis and Crohn's disease regarding their distribution by
      occupation, r = 0.36 and p < 0.05, as well as by industry, r = 0.37, p < 0.01.
      IBD mortality by occupation was significantly reduced among farmers (PMR: 70, 95%
      confidence interval [CI]: 42-97), mining machine operators (31, 95% CI: 0-74),
      and laborers (71. 95% CI: 45-98). A nonsignificant increase was found among sales
      persons (117, 95% CI: 95-139) and secretaries (122, 95% CI: 83-161). IBD
      mortality by industry was significantly reduced in agricultural production of
      livestock (39, 95% CI: 1-78), mining (46, 95% CI: 9-83), grocery stores (55, 95%
      CI: 17-94), and work in private households (64, 95% CI: 30-97). A nonsignificant
      increase was found in food production (128, 95% CI: 74-182), investment and
      insurance business (137, 95% CI: 77-198), and administration (122, 95% CI: 81
      163). CONCLUSIONS: IBD mortality is low in occupations associated with manual
      work and farming and relatively high in sedentary occupations associated with
      indoor work. Crohn's disease and ulcerative colitis show a similar distribution.

PMID- 11316155
TI  - Deficiency of colonic telomerase in ulcerative colitis.
AB  - OBJECTIVE: GI epithelial cells express telomerase, a ribonucleoprotein that
      prevents telomeric shortening in proliferating cells. Telomerase levels are high
      in cancer, but little is known about telomerase expression in other diseases. We,
      therefore, designed experiments to determine telomerase expression in different
      colonic segments and to compare this with corresponding segments in patients with
      ulcerative colitis. Colorectal cancers and adenomatous polyps were included as
      disease controls. METHODS: In total, telomerase expression was determined in
      colonic tissues obtained from 62 patients. Twenty-five patients had ulcerative
      colitis, 21 had normal colons, 11 had colorectal cancer, and nine had adenomatous
      polyps. Endoscopic biopsies were collected prospectively at colonoscopy,
      processed for telomerase assays (Telomeric Repeat Amplification Protocol),
      hematoxylin and eosin staining, and scored for inflammation. RESULTS: Telomerase
      activity is expressed in arbitrary units (median 95% confidence interval). In the
      normal colon, telomerase activity in the cecum, transverse, sigmoid, and rectum
      was 255 (171-449), 707 (374-895), 561 (468-1426), and 563 (402-846),
      respectively. Telomerase was higher in the distal three segments when compared
      with the cecum (p = 0.005). In ulcerative colitis, there was a marked decrease in
      telomerase activity in the cecum 152 (59-272), p = 0.04, transverse 180 (129
      365), p < 0.001, sigmoid 352 (114-464), p = 0.005, and rectum 180 (70-337), p =
      0.001 when compared with normals. Telomerase activity correlated negatively with
      inflammation (r = -0.32, p = 0.001) and was also decreased in microscopically
      normal areas. Cancers expressed high levels of telomerase. CONCLUSIONS: Colonic
      mucosal expression of telomerase is reduced in ulcerative colitis. Levels are low
      even in microscopically normal mucosa, suggesting that telomerase deficiency may
      contribute to the pathogenesis of the disease.

PMID- 11316156
TI  - The prevalence of celiac disease autoantibodies in patients with systemic lupus
      erythematosus.
AB  - OBJECTIVE: [corrected] Systemic lupus erythematosus has been associated with
      false positive autoantibodies for primary biliary cirrhosis, chronic active
      hepatitis, Sjogren's syndrome, rheumatoid arthritis, thyroid disorders, syphilis,
      and scleroderma. An increased prevalence of autoantibodies are found in celiac
      disease and systemic lupus erythematosus, which share the human lymphocyte HLA-B8
      and HLA-DR3 histocompatibility antigens. This study examines the prevalence of
      celiac disease autoantibodies in systemic lupus erythematosus patients. METHODS:
      Patients observed in the Department of Rheumatology at our institutions in San
      Antonio, Texas with known systemic lupus erythematosus were offered participation
      in the study. One hundred three of the 130 patients contacted agreed to
      participate. Patients were excluded if they were pregnant or medically unable to
      undergo endoscopy. All volunteers were tested for the serological presence of IgA
      and IgM antigliadin and IgA antiendomysial antibodies. Those with positive
      serology underwent esophagogastroduodenoscopy with duodenal mucosal biopsy.
      RESULTS: Twenty-four of 103 (23.3%) systemic lupus erythematosus patients tested
      positive for either antigliadin antibody, whereas none of the 103 patients tested
      positive for antiendomysial antibody. None of the 24 antigliadin positive
      patients were found to have endoscopic or histological evidence of celiac
      disease, making the false positive rate of antigliadin antibody 23%. CONCLUSION:
      The presence of false positive antigliadin antibodies in patients with systemic
      lupus erythematosus is common. Despite shared human lymphocyte antigen loci there
      does not seem to be an association between celiac disease and systemic lupus
      erythematosus.

PMID- 11316157
TI  - The prevalence of extraintestinal diseases in inflammatory bowel disease: a
      population-based study.
AB  - OBJECTIVE: The aim of this study was to determine the prevalence of the major
      extraintestinal manifestations of inflammatory bowel disease (IBD) and their
      relation to disease diagnosis and gender. METHODS: We used the population-based
      University of Manitoba IBD Database, which includes longitudinal files on all
      subjects of all health system contacts identified by International Classification
      of Diseases, 9th Revision, Clinical Modification codes for visit diagnosis. We
      extracted a cohort from our database, which included subjects with a known
      diagnosis of IBD for at least 10 yr. We then determined how many contacts each
      subject had for each of the following extraintestinal IBD-associated immune
      diseases: primary sclerosing cholangitis, ankylosing spondylitis, iritis/uveitis,
      pyoderma gangrenosum, and erythema nodosum. We calculated the prevalence of the
      extraintestinal diseases using an administrative definition of having at least
      five health system contacts for the diagnosis in question. This administrative
      definition has previously been validated in Crohn's disease and ulcerative
      colitis (UC). RESULTS: A total of 6.2% of patients with IBD had one of six major
      extraintestinal diseases studied in this report. Only 0.3% of patients had
      multiple extraintestinal diseases. Iritis/uveitis was the most common
      extraintestinal disease of all assessed (2.2% of women and 1.1% of men).
      Iritis/uveitis was more common among women, particularly those with UC (3.8%).
      Primary sclerosing cholangitis was most common among men with UC (3%). Ankylosing
      spondylitis was more common among men, and the highest rate was seen among men
      with Crohn's disease (2.7%). Pyoderma gangrenosum was more common in Crohn's
      (1.2%) with no gender predilection. Erythema nodosum was similarly present in
      Crohn's and UC but was more common among women (1.9%). CONCLUSIONS: The
      associations of immune mediated diseases in extraintestinal sites may help us to
      further our understanding of IBD pathogenesis, and it may help us in developing a
      paradigm of disease subsets.

PMID- 11316158
TI  - Appendectomy protects against the development of ulcerative colitis and reduces
      its recurrence: results of a multicenter case-controlled study in Japan.
AB  - OBJECTIVES: Studies in the US and Europe have shown that appendectomy may prevent
      the development of ulcerative colitis, but no detailed study has been conducted
      in Japan, where ulcerative colitis is uncommon and the population is racially
      homogeneous. In addition, there has been no detailed analysis of the relationship
      between appendectomy and the clinical course of ulcerative colitis. In this
      multicenter clinical study, we evaluated the effects of appendectomy on
      ulcerative colitis in Japan. METHODS: A case-control study was undertaken in
      seven medical institutions comparing the incidence of appendectomy and
      tonsillectomy in 325 patients with ulcerative colitis and 325 controls matched
      for age (10-yr intervals) and sex. Disease duration, extent, and prognosis were
      determined in 21 patients with ulcerative colitis who underwent appendectomies
      and 304 patients with ulcerative colitis who did not undergo appendectomies.
      RESULTS: Appendectomy was performed in a significantly lower percentage of
      patients in the ulcerative colitis group (21/325, 6.5%) than in the control group
      (53/325, 16.3%) (p < 0.001) (odds ratios = 0.355, 95% CI = 0.208-0.603). In
      contrast, no significant difference was observed between the groups with respect
      to tonsillectomy. The mean age (25.7 +/- 10.9 yr) of patients with ulcerative
      colitis at the time of appendectomy was significantly higher than the mean age
      (20.1 +/- 8.7 yr) of patients in the control group at the time of appendectomy (p
      < 0.05). The incidence of proctitis was higher in the appendectomy group than in
      the group that did not undergo appendectomies (38.1% vs 18.1%). In addition, the
      recurrence rates were significantly lower in the appenectomy group than in the
      group that did not undergo appendectomies (57. 1% vs 78.6%, p < 0.05), although
      both groups were similar in composition as to sex, age, duration of disease,
      smoking status, and previous medical treatment. CONCLUSIONS: Our results indicate
      that appendectomy has a negative association with and perhaps a preventive effect
      on the development of ulcerative colitis in the Japanese population. Furthermore,
      appendectomy also appears to reduce the extent and recurrence of ulcerative
      colitis.

PMID- 11316159
TI  - The IBD1 locus for susceptibility to Crohn's disease has a greater impact in
      Ashkenazi Jews with early onset disease.
AB  - OBJECTIVE: Recent studies have suggested that a susceptibility gene located on
      chromosome 16 and designated IBD1 may contribute to the development of Crohn's
      disease (CD). However, these findings were observed in predominantly non-Jewish
      populations; in the three studies where Ashkenazi Jews were included for
      analysis, the results have been widely divergent. Because Ashkenazi Jews are
      known to have a higher incidence of the disease than non-Jews, we sought to
      determine whether this previously reported linkage could be extended to the
      Ashkenazi population. In addition, we examined whether Ashkenazi Jewish patients
      with an early age of onset (< or = 21 yr) showed greater evidence of linkage to
      this locus. METHODS: Linkage analysis for the IBD1 region was performed on 123
      Ashkenazi Jewish CD patients distributed among 53 families. Only patients with
      four Jewish grandparents were considered to be Jewish. Of the 123 Ashkenazi
      Jewish patients, 75 (61%) had an age of onset < or = 21 yr. RESULTS: Ashkenazi
      Jews showed only modest evidence of linkage (nonparametric linkage 1.63, p =
      0.05) to the IBD1 locus. However, when the Ashkenazi population was subdivided on
      the basis of age of onset, there was a striking increase in linkage in families
      where affected individuals had an age of onset < or = 21 yr (nonparametric
      linkage 3.02, p = 0.002). In contrast, there was no evidence of linkage in the
      Jewish families where all affected individuals had an age of onset > 21 yr.
      CONCLUSIONS: The IBD1 gene plays a greater role in conferring susceptibility to
      CD in Jews with early onset disease than in Jews with late onset disease.

PMID- 11316160
TI  - Abdominal wall muscle activity in irritable bowel syndrome with bloating.
AB  - OBJECTIVE: Recurrent episodes of bloating and visible abdominal distension are
      common and distressing in irritable bowel syndrome, but the mechanisms are
      unknown. Patients often note that the distension is most pronounced in the
      upright posture, suggesting that the bloating may be the result of a decrease or
      absence of the normal rise in electromyograph activity in the abdominal wall
      muscles when standing. There are no reports of noninvasive electromyograph
      recordings of abdominal wall muscles in irritable bowel syndrome. We examined the
      hypothesis that abdominal distension is the result of relaxation of anterior
      abdominal wall musculature. METHODS: Studies were performed on patients with
      irritable bowel syndrome and a history of visible distension (n = 11, mean age
      48.6 yr, body mass index 24.8) and normal volunteers (n = 13, mean age 39.9 yr,
      body mass index 24.6). Surface recordings of muscle activity were made while
      subjects were lying, performing voluntary contraction of the abdominal wall, and
      standing. The examiners were blind as to the clinical status of the subjects.
      RESULTS: There were no differences in abdominal wall muscle activity (by
      electromyograph voltage) when comparing patients with irritable bowel syndrome to
      normal volunteers (e.g., relaxed lower abdomen supine mean electromyograph
      voltage in irritable bowel syndrome was 14.0 vs 14.6 in controls, p = 0.7, and
      relaxed lower abdomen standing in irritable bowel syndrome was 29.6 vs 25.2 in
      controls, p = 0.4). There was increased activity in both groups when contracting
      the muscles and when standing. CONCLUSIONS: Patterns of abdominal wall muscle
      activity do not differ between normal subjects and patients with irritable bowel
      syndrome. However, there is a clear increase in muscle activity in the standing
      position. Episodic distension is unlikely to be due to permanent anterior
      abdominal muscle weakness or a persistent inability of the muscles to activate
      with standing in irritable bowel syndrome.

PMID- 11316161
TI  - Efficacy of high-dose interferon in combination with ribavirin in patients with
      chronic hepatitis C resistant to interferon alone.
AB  - OBJECTIVE: Interferon combined with ribavirin has efficacy in the treatment of
      patients with chronic hepatitis C virus (HCV) infection. However, its utility in
      patients who have not responded to prior interferon therapy is not clear.
      Furthermore, the effect of using an increased dose of interferon in combination
      with ribavirin in patients with chronic hepatitis C resistant to conventional
      doses of interferon is not known. The aim of our study was to evaluate the effect
      of high-dose interferon in combination with ribavirin on the efficacy of treating
      patients with chronic hepatitis C resistant to interferon monotherapy in a large
      multicenter trial. METHODS: We randomized 154 patients with chronic hepatitis C
      who failed to achieve a sustained response with prior interferon therapy to
      receive either 3 or 5 MU of interferon alpha-2b and ribavirin (1000-1200 mg/day)
      for 12 months. There were 119 patients who had not responded and 35 who initially
      responded but relapsed after prior interferon monotherapy. Serum HCV RNA levels
      were measured at entry, 6, and 12 months of treatment and at the end of a 6-month
      follow-up period. RESULTS: The mean age of the subjects was 47 yr (range 28-68
      yr), and 110 (71.4%) were men. One hundred thirty-two patients (86%) had HCV
      genotype 1, whereas 21 (14%) had cirrhosis. Eighty-one subjects (53%) were
      randomized to receive 3 MU of interferon alpha-2b. Fifteen of 35 relapse subjects
      (43%) and 12 of 119 prior nonresponder entrants (10%) achieved a sustained
      virological response to the 12-month course of treatment. Overall, 11 of 81
      patients (14%) receiving 3 MU, and 16 of 73 patients (22%) receiving 5 MU of
      interferon maintained an undetectable HCV RNA level after cessation of therapy.
      The difference in sustained response rates between the two interferon dosage
      groups did not reach statistical significance (p = 0.09). However, among the
      nonresponder patients alone, there was an increased sustained response in the
      high-dose interferon group compared with the standard interferon dose group
      (15.5% vs 4.9%, p = 0.055). Twenty-six patients discontinued therapy before 6
      months, including 10 patients (12.3%) in the 3-MU and 16 patients (21.9%) in the
      5-MU groups (p = 0.17). CONCLUSIONS: Sustained virological response to combined
      interferon alpha-2b and ribavirin was significantly higher in relapse patients
      than those who did not respond to prior interferon monotherapy. Although, when
      all treated patients were analyzed, there was no significant difference in
      sustained response between subjects receiving 3 and 5 MU of interferon, among the
      prior nonresponder patients, treatment with 5 MU of interferon with ribavirin
      resulted in a slightly increased response compared with treatment with the
      standard interferon dosage. The tolerability of the treatment regimens was
      comparable.

PMID- 11316162
TI  - The utility of rifampin in diagnosing Gilbert's syndrome.
AB  - OBJECTIVE: The aim of this study was to evaluate the effect of rifampin (the
      "rifampin test") on serum bilirubin in patients with and without Gilbert's
      syndrome. METHODS: We conducted a clinical trial in which the effect of rifampin
      on serum bilirubin level in 15 patients with Gilbert's syndrome was compared with
      10 patients without Gilbert's syndrome (controls) in a General Internal
      Medicine/Primary Care clinic of a Veterans Affairs medical center. Each
      participant underwent a "rifampin test," i.e., bilirubin measurement at baseline
      and 2, 4, and 6 h after the administration of 900 mg of rifampin. Measurements
      included complete blood count, blood chemistry including liver panel tests (ALP,
      AST, LDH, and albumin) along with total serum bilirubin levels. Ten patients with
      Gilbert's and nine control patients had haptoglobin level measured at baseline
      and 6 h after the administration of rifampin. RESULTS: While fasting, the mean
      rise in total serum bilirubin at 2, 4, and 6 h after the administration of
      rifampin, respectively, was 0.5, 0.7, and 0.7 mg/dl (analysis of variance, p <
      0.001) in control patients and 0.6, 1.0, and 1.1 mg/dl (p < 0.001) in the study
      patients. In 15 fed subjects (six control and nine study), the mean rise in total
      serum bilirubin at 2, 4, and 6 h, respectively, was 0.3, 0.5, and 0.6 mg/dl (p <
      0.001) in controls and 0.5, 1.0, and 1.2 mg/dl (p < 0.001) in study subjects. In
      the fasting state, rise in total serum bilirubin to >1.9 mg/dl distinguished
      patients with Gilbert's syndrome from those without at 2, 4, and 6 h (sensitivity
      100%, 93%, and 93%; specificity 100%, 100%, and 100% at 2, 4, and 6 h,
      respectively). In the nonfasting state, rise in total serum bilirubin to > 1.5
      mg/dl at 4 and 6 h after rifampin administration distinguished the two groups
      (sensitivity 90% and 100%; specificity 100% and 100%, respectively). CONCLUSIONS:
      Rifampin increases total serum bilirubin levels in patients with and without
      Gilbert's syndrome. On fasting for 12 to 24 h, an absolute increase of bilirubin
      to >1.9 mg/dl 2 to 6 h after the administration of 900 mg of rifampin
      distinguishes patients with Gilbert's syndrome from those without it. In the
      nonfasting state, an increase in total serum bilirubin to > 1.5 mg/dl 4 to 6 h
      after the administration of rifampin distinguishes persons with Gilbert's
      syndrome from those without it.

PMID- 11316163
TI  - Effect of transjugular intrahepatic portosystemic shunt formation on portal
      hypertensive gastropathy and gastric circulation.
AB  - OBJECTIVES: The aim of this study was to investigate the effect of a transjugular
      intrahepatic portosystemic shunt (TIPS) on portal hypertensive gastropathy (PHG)
      and gastric hemodynamics. METHODS: A total of 16 patients with cirrhosis and
      portal hypertensive gastropathy were prospectively studied. Of these, 12 patients
      underwent TIPS for esophageal varices and four for refractory ascites. Gastric
      mucosal blood flow (GMBF) was assessed by laser Doppler flowmeter, and total
      blood flow (TBF) in submucosa and mucosa by near-infrared endoscopy. Portal
      venous pressure was obtained by a transducer during the TIPS procedure. The
      severity of portal hypertensive gastropathy was classified as none, mild, or
      severe. The examinations were performed before and 2 wk after the procedure.
      RESULTS: TIPS significantly reduced portal venous pressure. PHG improved in all
      four patients with severe PHG and in five of 12 patients with mild PHG after
      treatment. Gastric mucosal blood flow increased from 49.0 to 55.6 ml/min/100 g
      after TIPS. In contrast, TBF decreased from 0.35/s to 0.27/s after treatment.
      Liver function tests showed no significant changes before and after the
      procedure. CONCLUSIONS: It is considered that TIPS may have a beneficial effect
      on PHG at least for a short time. The mechanism by which PHG improves may be
      closely related to the improvement of the injured gastric perfusion in cirrhotic
      patients with PHG.

PMID- 11316164
TI  - Hepatocellular carcinoma in primary biliary cirrhosis: similar incidence to that
      in hepatitis C virus-related cirrhosis.
AB  - OBJECTIVES: The prevalence of hepatocellular carcinoma (HCC) in primary biliary
      cirrhosis (PBC) is not well established, as some reports suggest a low risk,
      whereas others indicate that HCC may be no less frequent than in other types of
      cirrhosis. METHODS: We compared the incidence of HCC in a series of 140 patients
      with PBC (five men, 135 women, mean age 54 +/- 1.6 yr) followed-up for a mean of
      period of 5.6 +/- 0.4 yr with a group of patients with cirrhosis related to
      hepatitis C virus (HCV) who were matched for age, sex, and follow-up period. In
      all patients, HCC was prospectively screened by clinical, laboratory, and
      ultrasound procedures. RESULTS: Five patients with PBC (3.6%) developed HCC. All
      were in stage IV of the disease. The incidence of HCC in the 45 patients with
      late stages of the disease (III or IV) was 11.1%, similar to that found in
      patients with HCV-related cirrhosis, which was 15.0%. The relative risk for HCC
      in late stages of PBC was of 0.812 (95% CI, 0.229-2.883) with respect to HCV
      related cirrhosis. The probability for developing HCC was significantly higher in
      patients with HCV-related cirrhosis than in PBC patients overall (p = 0.001), but
      was similar in patients with HCV-related cirrhosis and in patients with PBC in
      stages III and IV (p = ns). CONCLUSION: The risk for HCC in patients with late
      stages of PBC is similar to that in patients with HCV-related cirrhosis.

PMID- 11316165
TI  - Treatment of cholangiocarcinoma complicating primary sclerosing cholangitis: the
      Mayo Clinic experience.
AB  - OBJECTIVES: The aims of this retrospective study were to assess the frequency
      with which we used different treatment modalities for patients with primary
      sclerosing cholangitis (PSC) and cholangiocellular carcinoma (CCA). METHODS: A
      total of 41 patients with known CCA complicating PSC with a median age of 49 yr
      (range, 27-75 yr) were identified from a group of 1009 patients (4%) with PSC
      seen over 10 yr at the Mayo Clinic. RESULTS: These patients received mainly five
      forms of treatment: 10 patients were treated with radiation therapy (RT) with or
      without 5-fluorouracil (5-FU) (seven with palliative and three with curative
      intent), nine with stent placement for cholestasis, 12 with conservative
      treatment, four with surgical resection (one of four received RT and 5-FU), and
      three patients with orthotopic liver transplantation and RT, with or without 5
      FU. One patient was treated with 5-FU alone, one with photodynamic therapy, and
      one patient with somatostatin analog. A total of 36 patients died, whereas four
      (10%) patients survived (two with surgical resection, one with orthotopic liver
      transplantation and RT, and one with stent placement) during a median follow-up
      of 5.5 months (range, 1-75 months). One patient was lost to follow-up.
      CONCLUSIONS: In highly selective cases, resective surgery seems to be of benefit
      in PSC patients with CCA. However, these therapies are rarely applied to these
      patients because of the advanced nature of the disease at the time of diagnosis.
      Efforts should be directed at earlier identification of potential surgical
      candidates.

PMID- 11316166
TI  - Efficacy of interferon for chronic hepatitis C virus-related hepatitis in kidney
      transplant candidates on hemodialysis: results after transplantation.
AB  - OBJECTIVES: Interferon-alpha (IFN) may have undesirable effects on a functioning
      graft. The aim of this study was to evaluate IFN treatment in kidney transplant
      candidates during the hemodialysis period as well as the results after
      transplantation. METHODS: A total of 29 noncirrhotic hemodialysis patients with
      chronic hepatitis C virus (HCV) infection (based on long-term rise in ALT, HCV
      serology, HCV RNA by polymerase chain reaction methods, and histological
      evidence) were included. Tolerability to IFN treatment, pre- and
      posttransplantation therapeutic results, and long-term outcome were recorded. IFN
      regimen consisted of 3 million units (MU) times per week after hemodialysis
      sessions for 6 months, followed by 1.5 MU after each hemodialysis session for an
      additional 6 months. All patients gave informed consent for participation.
      RESULTS: IFN therapy was fairly well tolerated. Adverse effects due to IFN
      toxicity, renal disease, or causes related to the immunological properties of IFN
      were observed in 24% of patients. At the end of treatment, ALT had normalized in
      23/28 patients (82.1%), and HCV RNA had cleared in 23/28 patients (82.1%). During
      follow-up, HCV RNA was persistently negative in 18 patients (64%, including
      transplant recipients). A total of 14 patients (nine HCV RNA-negative) received a
      kidney transplant. Mean follow-up after the procedure was 41 +/- 28 months. In
      all, 12 patients had a functioning graft, one had acute vascular rejection, and
      one died of carcinoma. All transplanted patients maintained normal ALT levels,
      and eight remained HCV RNA-negative. CONCLUSIONS: Treatment results in our study
      population were better than those observed in the general population. The long
      term response achieved, which was maintained after transplantation, supports the
      use of IFN for HCV hepatitis in kidney transplant candidates under hemodialysis.

PMID- 11316167
TI  - The metabolism of nicotinamide in human liver cirrhosis: a study on N
      methylnicotinamide and 2-pyridone-5-carboxamide production.
AB  - OBJECTIVES: Nicotinamide methylation followed by urinary excretion of N
      methylnicotinamide increases in cirrhotic patients, despite the derangement of
      the overall methylation processes in liver disease. The rise in N
      methylnicotinamide could depend, at least in part, on a reduced transformation of
      this molecule into 2-pyridone-5-carboxamide. The aim of this study was to
      investigate this hypothesis. METHODS: Serum and urinary levels (mean +/- SEM) of
      N-methylnicotinamide and urinary excretion of 2-pyridone-5-carboxamide were
      measured in 10 healthy controls and 10 patients with liver cirrhosis in basal
      conditions and after a nicotinamide oral load (1.5 mg/kg body weight). RESULTS: N
      methylnicotinamide serum levels increased significantly (p < 0.01) in cirrhotic
      patients compared to controls, both as basal values (0.43 +/- 0.07 nmol/ml; 0.15
      +/- 0.01) and as area under the curve 5 h after a nicotinamide load (cirrhotics:
      562.4 +/- 50.5 nmol/ml x min; controls: 314.4 +/- 23.8). Twenty-four-hour urinary
      excretion of N-methylnicotinamide and 2-pyridone-5-carboxamide was also
      significantly (p < 0.05) increased in cirrhotic patients versus controls, both in
      basal conditions (N-methylnicotinamide: 82.0 +/- 8.4 micromol, 48.8 +/- 4.8; 2
      pyridone-5-carboxamide: 129.3 +/- 23.0, 64.6 +/- 9.8) and after a nicotinamide
      oral load (N-methylnicotinamide: 290.1 +/- 23.1, 180.8 +/- 7.4; 2-pyridone-5
      carboxamide: 694.7 +/- 32.5, 391.0 +/- 21.9). Moreover, 24 h N
      methylnicotinamide/2-pyridone-5-carboxamide ratio was similar in patients and
      controls (basal: 0.78 +/- 0.39, 0.90 +/- 0.51; load: 0.42 +/- 0.11, 0.48 +/-
      0.16). CONCLUSIONS: In cirrhotic patients nicotinamide methylation is increased,
      as shown by the rise in urinary N-methylnicotinamide and 2-pyridone-5-carboxamide
      that is concurrent and proportional (constant 24-h metabolite ratio). The
      hyperfunction of this methylating pathway might play a protective role against
      the toxic effect of intracellular accumulation of nicotinamide deriving from the
      catabolic state of cirrhosis.

PMID- 11316168
TI  - Correlation of mutational analysis to clinical features in Taiwanese patients
      with Gilbert's syndrome.
AB  - OBJECTIVES: Mutations in the promoter as well as in the coding region of the
      bilirubin UDP-glucuronosyltransferase gene (UGT1A1) have been found to be
      associated with Gilbert's syndrome. However, the genetic basis of Gilbert's
      syndrome in our population and correlation of these mutations to fasting serum
      bilirubin levels in patients with Gilbert's syndrome remain to be clarified.
      METHODS: We applied polymerase chain reaction-based direct-sequencing assays to
      examine mutations in UGT1A1 gene in 20 unrelated Gilbert's patients and in a
      family with Gilbert's syndrome. RESULTS: We studied three mutations that were
      previously reported to be associated with Gilbert's syndrome (i.e., the TATAA-box
      mutation, Gly71Arg, and Pro229Gln) in 20 patients with Gilbert's syndrome. Of the
      patients, 16, five, and six were found to have the TATAA-box, Gly71Arg and
      Pro229Gln mutations, respectively. Seven patients had simultaneous mutations both
      in the TATAA box and in the coding region. Of note, all six patients with
      Pro229Gln also had the TATAA-box mutation. Localization of Pro229Gln on the
      allele containing the TATAA-box mutation was demonstrated in a family with
      Gilbert's syndrome. The patients simultaneously heterozygous for both the TATAA
      box mutation and Gly71Arg usually had serum bilirubin levels similar to those
      found in the patients homozygous for the TATAA-box mutation, but usually higher
      than those found in the patients heterozygous for the TATAA-box mutation alone.
      On the other hand, concurrence of Pro229Gln in patients with TATAA-box mutation
      or with Gly71Arg did not significantly affect serum bilirubin levels.
      CONCLUSIONS: The TATAA-box mutation and Gly71Arg are the major causes for
      Gilbert's syndrome in our population. Concurrence of mutations of Gly71Arg and
      TATAA-box usually exerts a synergistic effect on hyperbilirubinemia. Pro229Gln,
      which is regularly linked to the TATAA-box mutation, may not have a significant
      effect on serum bilirubin levels.

PMID- 11316169
TI  - Serum xanthine oxidase in human liver disease.
AB  - OBJECTIVES: High concentrations of serum xanthine oxidase (XO) have been reported
      during human liver disease and hepatocyte injury in experimental settings.
      However, it is unclear whether this elevation reflects hepatocyte necrosis or has
      a different meaning. METHODS: The serum level of XO in 64 patients with chronic
      liver disease (17 patients with cirrhosis, 30 with chronic hepatitis, and 17 with
      cholestatic disorders) and in 12 control subjects was determined by a competitive
      ELISA. Conventional serum markers of liver damage were assessed in all patients,
      and grading and staging were scored in the chronic hepatitis group according to
      Knodell. RESULTS: The XO serum levels were significantly higher in the patients
      than in the controls. The differences were also significant when controls were
      compared to patients with chronic hepatitis and cholestatic disorders separately,
      but not when compared to the cirrhosis group. Patients with cholestatic disorders
      had XO values higher than those of patients with cirrhosis or chronic hepatitis.
      XO levels did not correlate with stage and grade in chronic hepatitis group. We
      found a weak but significant positive correlation in patients between XO serum
      level and gamma-glutamyl transpeptidase (r = 0.37). This correlation was stronger
      when chronic hepatitis (r = 0.42) and, especially cholestatic disorders (r =
      0.71), were separately tested, but was absent in the cirrhosis group. The XO
      values positively correlated with alkaline phosphatase in patients with
      cholestatic disorders. A level of serum XO >32 microg/ml specifically identified
      cholestatic disorders in our study population. CONCLUSIONS: A marked elevation of
      serum XO in patients with chronic liver disease seems to reflect the presence of
      cholestasis. No correlation between XO levels and histological or serum evidence
      of hepatocyte necrosis was found in these patients.

PMID- 11316170
TI  - Obesity and female gender increase breath ethanol concentration: potential
      implications for the pathogenesis of nonalcoholic steatohepatitis.
AB  - OBJECTIVES: Similarities between histological features of alcoholic hepatitis and
      obesity-related liver disease suggest a common pathogenic mechanism. Because
      intestinal bacteria can produce ethanol, it is conceivable that intestinally
      derived alcohol may contribute to fatty liver disease. An indirect way of
      measuring endogenous ethanol is to measure the breath ethanol concentration. In a
      previous study in ob/ob mice, breath ethanol decreased with a course of non
      absorbable antibiotics, suggesting that the ethanol is derived from intestinal
      bacterial flora. The aims of this study were 1) to determine whether alcohol can
      be detected in the breath of human subjects, and 2) to assess whether there is
      any correlation between ethanol and obesity in patients with nonalcoholic
      steatohepatits (NASH) and control subjects without known liver disease. METHODS:
      Breath ethanol concentration was determined in 21 patients with biopsy-proven
      NASH and in 10 control subjects by gas chromatography. An abnormal breath ethanol
      level was defined as two standard deviations above the mean value of the breath
      ethanol of lean controls. RESULTS: Minute quantities of ethanol were detected in
      the breath of human subjects who had not consumed alcohol in the recent past.
      Patients who were obese were more likely to have higher breath ethanol
      concentrations. Women also had higher breath alcohol than men. However, there was
      no difference between patients with NASH and controls. Severity of liver disease,
      as evidenced by cirrhosis, did not influence the breath ethanol concentration.
      CONCLUSIONS: Higher breath ethanol concentrations are observed in obese subjects
      than in leaner ones. It is possible that intestinally derived ethanol may
      contribute to the pathogenesis of NASH.

PMID- 11316171
TI  - Relationship between pre-TIPS liver perfusion by the portal vein and the
      incidence of post-TIPS chronic hepatic encephalopathy.
AB  - OBJECTIVE: In the present study we evaluated the predictive value of
      pretransjugular intrahepatic portosystemic shunt (TIPS) portal perfusion as
      assessed by Doppler ultrasonography for the onset of chronic encephalopathy after
      TIPS. METHODS: A total of 231 cirrhotic patients were followed-up prospectively
      after TIPS placement. The pattern of intrahepatic portal flow was assessed before
      TIPS. Patients were divided into two groups according to Doppler findings. Group
      1 comprised patients with prograde portal flow (n = 200), whereas group 2
      comprised those with loss of portal perfusion (hepatofugal or back-and-forth flow
      or portal vein thrombosis; n = 31). The presence of chronic encephalopathy during
      a median follow-up of 32 months was prospectively recorded. The prognostic value
      of the following parameters for the onset of chronic recurrent encephalopathy
      after TIPS was evaluated: age, presence of encephalopathy before TIPS,
      alcoholism, Pugh score, and loss of portal perfusion before TIPS. The independent
      prognostic value of each variable was tested with a multiple logistic regression
      analysis. RESULTS: The two groups were comparable in terms of age, incidence of
      prior episodes of hepatic encephalopathy, and portacaval gradient before and
      after the procedure; however, liver failure was more severe in patients in group
      2 (Pugh score: 9.2 +/- 1.9 vs 10.3 +/- 1.7). The 3-yr survival was identical for
      both groups; 25% of the 200 patients in group 1 developed chronic encephalopathy
      as compared to 6% of the 31 patients in group 2 (p = 0.03). Multiple logistic
      regression analysis demonstrated that loss of portal perfusion and age >65 yr
      were the only independent predictors of the onset of post-TIPS chronic
      encephalopathy (odds ratios 0.24 and 1.98, respectively). CONCLUSIONS: Cirrhotic
      patients with loss of portal perfusion before TIPS were protected against post
      TIPS chronic hepatic encephalopathy despite a more severe liver dysfunction at
      baseline. The only other independent predictive factor for the onset of this
      complication was age.

PMID- 11316172
TI  - Hemodynamic effects of a combination of prazosin and terlipressin in patients
      with viral cirrhosis.
AB  - OBJECTIVES: Terlipressin reduces portal pressure in cirrhotic patients mainly
      through intense splanchnic vasoconstriction that decrease portal venous inflow.
      Hepatic blood flow may also be reduced by terlipressin. Prazosin (an alpha1
      adrenoceptor antagonist) has also been proposed to decrease portal pressure in
      cirrhotic patients possibly through a decrease in the intrahepatic vascular
      resistance. The current study was aimed to evaluate whether a combination of
      prazosin and terlipressin exerts more beneficial effects than terlipressin alone.
      METHODS: Patients were randomly assigned to receive either a placebo (n = 12) or
      an oral administration of prazosin 2 mg (n = 12). Thereafter, each patient
      received an intravenous injection of terlipressin 2 mg. Hemodynamic values were
      measured basally, 30 min after prazosin or placebo, and 30 min after
      terlipressin. RESULTS: Placebo administration did not affect any hemodynamic
      values. Terlipressin administration, on the other hand, resulted in expected
      changes on the hepatic venous pressure gradient, hepatic blood flow, and systemic
      hemodynamics. In contrast, prazosin significantly decreased hepatic venous
      pressure gradient with an increased hepatic blood flow and intrinsic hepatic
      clearance. After terlipressin administration, a further decrease in hepatic
      venous pressure gradient was observed with preservation of hepatic blood flow and
      intrinsic hepatic clearance. The magnitude of decrease in hepatic venous pressure
      gradient was more profound in patients receiving prazosin plus terlipressin than
      in those receiving terlipressin alone. However, the magnitude of changes in
      systemic hemodynamics was no different between the two groups of patients.
      CONCLUSIONS: The current study showed that a combination of prazosin and
      terlipressin resulted in a more profound reduction of hepatic venous pressure
      gradient with a preservation of hepatic blood flow and intrinsic hepatic
      clearance than did terlipressin alone. However, the combined therapy did not
      modify the systemic hemodynamic effects exerted by terlipressin.

PMID- 11316173
TI  - Effects of high-volume plasmapheresis on ammonia, urea, and amino acids in
      patients with acute liver failure.
AB  - OBJECTIVE: In acute liver failure (ALF), urea production is severely impaired,
      and detoxification of ammonia by glutamine synthesis plays an important
      protective role. The aim of this study was to examine the effects of therapeutic
      high-volume plasmapheresis (HVP) on arterial concentrations and splanchnic
      exchange rates of ammonia, urea, and amino acids-in particular, glutamine.
      METHODS: A quantity of 8 L of plasma was exchanged over the course of 7 h in 11
      patients with ALF after development of hepatic encephalopathy grade III-IV.
      Splanchnic exchange rates of ammonia, urea, and amino acids were measured by use
      of liver vein catheterization. RESULTS: HVP removed ammonia and glutamine at a
      rate of 1 micromol/min and 27 micromol/min, respectively. Arterial ammonia
      decreased from 160 +/- 65 to 114 +/- 50 micromol/L (p < 0.001). In contrast,
      arterial glutamine was only minimally changed from 1791 +/- 1655 to 1764 +/- 1875
      micromol/L (NS). This implied that the rate of systemic glutamine synthesis was
      increased by 27 micromol/min. Splanchnic exchange rates (before vs after HVP)
      were as follows: for ammonia, -93 +/- 101 versus -70 +/- 80 micromol/min (NS);
      urea-nitrogen, 0.08 +/- 1.64 versus -0.31 +/- 0.45 mmol/min (NS); alanine, -73 +/
      151 versus 12 +/- 83 micromol/min (p < 0.05); and glutamine: 132 +/- 246 versus
      186 +/- 285 micromol/min (NS), with negative values denoting release.
      CONCLUSIONS: Arterial ammonia decreased during HVP in patients with ALF. The data
      suggest that this effect of HVP could be explained by increased hepatic urea
      synthesis and possibly by increased glutamine synthesis in muscle tissue.

PMID- 11316174
TI  - Understanding the pathogenesis of autoimmune hepatitis.
AB  - OBJECTIVES: The aim of this study was to review the pathogenic mechanisms of
      autoimmune hepatitis, identify gaps in knowledge, and focus future investigative
      efforts. METHODS: The study was based on a review of all relevant articles on the
      mechanisms of autoimmunity in autoimmune liver disease from 1980 to 2000,
      extraction of pertinent concepts from the medical literature; and integration of
      evolving paradigms of pathogenesis with personal experiences and investigations.
      RESULTS: Autoimmune hepatitis is a consequence of autoantigen exposure, genetic
      predisposition, and defective immunoregulatory mechanisms. Autoantigen is
      optimally presented by class II molecules of the major histocompatibility complex
      that have lysine residues at position DRbeta71 of the antigen-binding groove.
      Cytokines and non-disease-specific autoimmune promoters modulate immune
      reactivity. Cell-mediated and antibody-dependent mechanisms contribute to
      hepatocyte injury. CONCLUSIONS: Multiple disturbances in the homeostatic
      mechanisms that preserve self-tolerance are likely in autoimmune hepatitis.
      Future investigations must focus on individual determinants of autoantigen
      presentation, immunocyte activation, and liver cell destruction. Findings can
      then be integrated into a comprehensive knowledge base that may be applicable to
      other autoimmune diseases.

PMID- 11316175
TI  - Spontaneous bacterial peritonitis--in-hospital mortality, predictors of survival,
      and health care costs from 1988 to 1998.
AB  - OBJECTIVES: Spontaneous bacterial peritonitis (SBP) is a complication of end
      stage liver disease with a reported mortality of 30-50%. In this study, we
      investigated the outcome of all patients admitted to Maryland hospitals with SBP
      from 1988 to 1998. Main outcomes considered included trends in survival rates
      over time, changes in the length of stay, total health care costs, and variables
      that predicted survival rates. METHODS: We used the Maryland Health Services Cost
      Review database of all patients admitted to Maryland hospitals with an
      International Classification of Diseases (Ninth Revision) code for both
      peritonitis and cirrhosis from 1988 to 1998. RESULTS: A total of 348 patients
      were admitted with an in-hospital mortality of 32.6%; there was no significant
      change in mortality rate during this period. The survival rate was similar in the
      university and community hospitals. In the logistic regression analysis, age (p =
      0.001) and intensive care unit stay (p = 0.0001) were found to significantly
      influence the survival rates; those patients who had an intensive care unit stay
      were 2.8 times more likely to die than those who did not have an intensive care
      unit stay, controlling for age. The average length of hospital stay remained
      unchanged (13.5 +/- 12.7 days) during the study period. Although the median
      hospital charge (excluding professional fees) remained unchanged, mean inflation
      adjusted charges increased from $7,897 in 1988 to $25,902 in CONCLUSIONS: The
      mortality rate associated with SBP has remained unchanged over an 11-yr period
      from 1988 to 1998. The mortality showed a strong correlation with age and
      intensive care unit stay. The median hospital stay and median charges remained
      unchanged during this period, but mean costs increased significantly because of
      increased use of resources by a few patients.

PMID- 11316176
TI  - Factors predicting interferon treatment response in patients with chronic
      hepatitis c: late viral clearance does not preclude a sustained response.
AB  - OBJECTIVES: Because of the suboptimal efficacy, cost, and adverse effects of
      interferon in chronic hepatitis C (HCV), predictors have been sought to detect
      patients with a good treatment response. Also, markers for determining a poor
      response early in the course of therapy, such as the lack of early viral
      clearance, have been proposed. METHODS: Ninety-seven patients with chronic
      hepatitis C were enrolled to receive leukocyte alpha-interferon according to a
      stepped-care management protocol. The final virological treatment response was
      evaluated in 74 patients after a 6-month post-treatment follow-up. The
      relationship between pretreatment and during-treatment variables and the long
      term response was assessed. RESULTS: Non-1 viral genotype, higher pretreatment
      ALT levels, and lower gamma-glutamyl transferase (GGT)/ALT ratios and GGT as well
      as younger age were significantly associated with a sustained response; a trend
      was also detected for lower serum ferritin levels. Normalization of ALT by 3
      months was also a significant predictor of a long-term response. Of the 27
      patients carrying the HCV genotype 3a, seven (26%) were still HCV RNA positive at
      6 months. Of these patients, however, five (19%) still achieved a sustained
      virological response after treatment for up to 12 months. CONCLUSIONS: In
      contrast to some previous reports, our results suggest that a late viral
      clearance after 6 months of interferon monotherapy may not preclude a favorable
      long-term response after a 12-month treatment, especially in patients carrying a
      non-1 HCV genotype. A low pretreatment GGT/ALT ratio is a predictor of a good
      treatment response.

PMID- 11316177
TI  - Prognostic factors after hepatic resection for hepatocellular carcinoma with
      hepatitis C viral infection: univariate and multivariate analysis.
AB  - OBJECTIVES: Although the incidence of hepatocellular carcinoma (HCC) with
      hepatitis C virus (HCV) infection is higher than in patients with hepatitis B
      virus (HBV)-related HCC in Japan, the long-term prognosis and prognostic factors
      of HCV-related HCC after hepatic resection are poorly understood. METHODS: The
      surgical outcome of HCV-related HCC in 172 consecutive patients who underwent
      hepatic resection between 1989 and 1997 was retrospectively clarified.
      Postresection prognostic factors were evaluated by univariate and multivariate
      analysis using Cox's proportional hazards model. RESULTS: The overall incidence
      of postoperative complications was 23.2%, and 11 patients among that group had
      hospital deaths (6.4%) including 9 (5.2%) operative deaths. The mean and median
      overall survivals including hospital death after surgery were 41 months and 33
      months, respectively. The 3-, 5-, and 7-yr overall survival rates after hepatic
      resection were 63%, 52%, and 47%, respectively. The 3-, 5-, and 7-yr disease-free
      survival rates after hepatic resection were 33%, 20%, and 15%, respectively.
      Multivariate analysis revealed that serum alpha-fetoprotein (AFP) of > or = 1000
      ng/ml and the presence of vascular invasion were independent unfavorable
      prognostic factors affecting overall survival and that AFP of > or = 1000 ng/ml
      was an independently significant factor of poor disease-free survival.
      CONCLUSIONS: We found the postresection survival of patients with HCV-related HCC
      should be stratified by the high value of AFP and the presence of vascular
      invasion. AFP may be the most powerful predictor of the long-term prognosis and
      recurrence in such patients.

PMID- 11316178
TI  - Long-Term treatment with cisapride and antibiotics in liver cirrhosis: effect on
      small intestinal motility, bacterial overgrowth, and liver function.
AB  - OBJECTIVES: Altered small-bowel motility, lengthening of the orocecal transit
      time, and small-intestinal bacterial overgrowth have been described in patients
      with liver cirrhosis. These changes might be related to the progressive course
      and poor prognosis of the disease. We investigated the effect of a long-term
      treatment with cisapride and an antibiotic regimen on small-intestinal motor
      activity, orocecal transit time, bacterial overgrowth, and some parameters of
      liver function. METHODS: Thirty-four patients with liver cirrhosis of different
      etiology entered in the study. They were randomly allocated to receive cisapride
      (12), an alternating regimen of norfloxacin and neomycin (12), or placebo (10)
      during a period of 6 months. At entry and at 3 and 6 months, a stationary small
      intestinal manometry was performed, and orocecal transit time and small
      intestinal bacterial overgrowth were also investigated using the H2 breath test.
      Liver function was estimated with clinical and laboratory measurements (Child
      Pugh score). RESULTS: After 6 months, both cisapride and antibiotics
      significantly improved fasting cyclic activity, reduced the duration of orocecal
      transit time, and decreased small-intestinal bacterial overgrowth. Cisapride
      administration was followed also by an increase in the amplitude of contractions.
      No statistically significant variations in these parameters were observed with
      placebo. An improvement of liver function was observed at 3 and 6 months with
      both cisapride and antibiotics. CONCLUSIONS: Long-term treatment with cisapride
      or antibiotics reversed altered small-intestinal motility and bacterial
      overgrowth in patients with liver cirrhosis. These findings suggest a possible
      role for prokinetics and antibiotics as a modality of treatment in selected cases
      of decompensated cirrhosis.

PMID- 11316179
TI  - An audit of the utility of in-patient fecal occult blood testing.
AB  - OBJECTIVES: Recent surveys of physician practice have suggested the existence of
      excessive, inappropriate use of the fecal occult blood test (FOBT). We studied
      the implementation of this test in hospitalized patients. METHODS: We performed a
      retrospective chart review of 1000 randomly selected patients who had been
      discharged from the Medicine service at four teaching hospitals. Patient
      demographics, clinical presentation, presence or absence of overt GI bleeding,
      and use of medications that might affect the FOBT were recorded. Reviewers
      assessed whether patients who had FOBT would have been candidates for colon
      resection if asymptomatic colon cancer had been found. RESULTS: Digital rectal
      examination was documented in 44.8% of patients; the findings were recorded in
      only 9%. A total of 421 patients had FOBT on admission, usually on stool obtained
      at digital rectal examination. Of the patients with a positive FOBT, 17% had
      active GI bleeding. Only 41.1% of patients with a positive FOBT were referred to
      the gastroenterology service. In 70.5% of patients, FOBT could be considered
      inappropriate because of factors such as age, active GI bleeding, or use of
      aspirin or other nonsteroidal anti-inflammatory drugs. CONCLUSIONS: The FOBT,
      which is validated only for colorectal cancer screening, is often performed
      inappropriately in patients admitted to the hospital. This test should be
      restricted in hospital practice. It would be preferable to identify patients who
      are appropriate candidates for colorectal cancer screening at the time of
      hospital discharge and to advise them about the appropriate performance of the
      FOBT at home.

PMID- 11316180
TI  - Possible role of telomerase activation in the multistep tumor progression of
      periampullary lesions in patients with familial adenomatous polyposis.
AB  - OBJECTIVES: The role of telomerase in periampullary tumor progression in patients
      with familial adenomatous polyposis (FAP) was investigated. METHODS: Relative
      telomerase activity was measured using a telomerease amplification protocol in
      periampullary biopsy specimens of normal mucosa and adenoma obtained from
      patients with FAP, and was compared with that of periampullary normal mucosa and
      cancer specimens from patients without FAP. RESULTS: None of normal mucosa from
      the non-FAP patients showed a telomerase ladder. Telomerase was positively
      detected in three of seven normal mucosa (42.9%) and in five of seven adenoma
      from FAP patients (62.5%). In papillary cancer from the non-FAP patients, seven
      of nine tissue specimens (77.8%) showed positive activity. When
      semiquantitatively analyzed, the relative telomerase activity increased in
      accordance with the progression of the diseases. CONCLUSIONS: Telomerase is
      activated even in normal mucosa of FAP patients, and the intensities of
      telomerase may reflect the malignant potential of periampullary neoplasms.

PMID- 11316181
TI  - Narcotic analgesic effects on the sphincter of Oddi: a review of the data and
      therapeutic implications in treating pancreatitis.
AB  - OBJECTIVE: Traditional teaching dictates that morphine induces "spasm" in the
      sphincter of Oddi (SO) and should not be used in acute pancreatitis and that
      meperidine is the analgesic of choice because it does not elevate SO pressures. A
      literature search and review was performed to evaluate this teaching examining
      the effect of narcotic analgesic's effects on SO. METHODS: A Medline search was
      performed using keywords and phrases. The manufacturers of meperidine were
      contacted and their reports and studies were obtained and reviewed. RESULTS:
      Initial studies measured biliary pressure after narcotic administration in
      animals, and postoperative and intraoperative cholecystectomy patients. All
      narcotics increased biliary pressure, but morphine was associated with the
      largest elevation. Later studies using endoscopic retrograde
      cholangiopancreatography with direct SO manometry demonstrated that the SO is
      exquisitely sensitive to all narcotics including meperidine and that a small
      increase in biliary sphincter pressure is seen with higher doses of morphine. All
      narcotics increase SO phasic wave frequency and interfere with SO peristalsis.
      CONCLUSIONS: Narcotic-induced increases in phasic wave frequency interfere with
      SO filling and are responsible for the increase in bile duct pressure seen on the
      initial studies. No studies directly compare the effects of meperidine or
      morphine on SO manometry and no comparative studies exist in patients with acute
      pancreatitis. No outcome-based studies comparing these drugs have been performed
      in patients with acute pancreatitis. Morphine may be of more benefit than
      meperidine by offering longer pain relief with less risk of seizures. No studies
      or evidence exist to indicate morphine is contraindicated for use in acute
      pancreatitis.

PMID- 11316182
TI  - X-ray tube.

PMID- 11316183
TI  - Postinfantile giant cell hepatitis complicating ulcerative colitis: a case report
      and review of the literature.
AB  - Giant cell hepatitis is common in the neonatal period. When present in adults, it
      is known as postinfantile giant cell hepatitis (PGCH). PGCH can arise in the
      context of viral, drug-related, and autoimmune disorders but, in many other
      cases, its etiology remains unclear. We report a case of PGCH occurring in the
      setting of autoimmune hepatitis and ulcerative colitis. This case highlights the
      close association between PGCH and autoimmune disorders and the need to recognize
      it as a hepatic complication of inflammatory bowel disease.

PMID- 11316184
TI  - Massive progression of diffuse hepatic lymphangiomatosis after liver resection
      and rapid deterioration after liver transplantation.
AB  - Hepatic involvement is an exceptional presentation of lymphangiomatosis. In this
      case report we describe a patient who underwent liver transplantation secondary
      to progressive hepatic involvement, which occurred 2 yr after partial
      hepatectomy. Within 1 yr after liver transplantation the disease condition
      deteriorated, with rapid progression of pre-existing skeletal lesions and
      development of pulmonary disease. We conclude that liver transplantation may be a
      treatment option for hepatic lymphangiomatosis. In the presence of pre-existing
      extrahepatic lesions, however, liver transplantation seems to be contraindicated.

PMID- 11316185
TI  - Generalized intestinal dysmotility in a patient with syringomyelia.
AB  - Syringomyelia is a rare degenerative disorder of the spinal cord that causes
      progressive neurological dysfunction. Patients with syringomyelia have a variety
      of gastrointestinal symptoms although there are limited data on the frequency or
      the severity of these complaints. In this case report we describe a 65-yr-old man
      with syringomyelia and gastrointestinal dysmotility at multiple levels as
      documented by esophageal motility study, gastric emptying scan, antroduodenal
      motility study, and anorectal manometry. The patient's nausea, recurrent
      vomiting, and fecal incontinence were treated successfully with dietary changes,
      a promotility agent, and a bowel training regimen. This report highlights the
      need for more objective studies of gastrointestinal motility in patients with
      syringomyelia.

PMID- 11316186
TI  - A homozygous missense mutation in the tyrosine E kinase domain of the RET proto
      oncogene in an infant with total intestinal aganglionosis.
AB  - Germline mutations of the RET proto-oncogene (RET), its ligand glial cell-derived
      neurotrophic factor (GDNF), and neurturin (NTN) gene have been reported in
      patients with Hirschsprung's disease. A targeted mutation in the tyrosine kinase
      domain of RET produced total intestinal aganglionosis and renal agenesis in
      homozygous transgenic mice. Here we describe a homozygous mutation of the human
      gene for the RET tyrosine kinase domain that was present in a male neonate with
      total intestinal aganglionosis. Gut wall biopsy specimens from the stomach to the
      anorectum showed no ganglion cells. No urinary tract abnormalities were detected.
      Genomic DNAs were isolated from peripheral blood lymphocytes of the infant and
      his parents. DNA sequences of all the RET/GDNF/NTN coding regions were determined
      using a direct DyeDeoxy Terminator Cycle method. A homozygous missense mutation
      (CGG-to-TGG) at RET codon 969 was identified in this patient, which resulted in
      an amino acid change from arginine to tryptophan. No germline RET/GDNF/NTN
      mutations were found in his parents. In this case, the homozygous RET mutation
      seemed to cause a critical alteration of the Ret tyrosine kinase activity, which
      resulted in total intestinal aganglionosis but not renal agenesis. Discrepancies
      in phenotypic expression between humans and mice suggest differing threshold
      values for RET signal transduction in species or organs.

PMID- 11316187
TI  - Asymptomatic nonpathological persistent elevation of pancreatic enzymes: an
      inherited disorder?

PMID- 11316188
TI  - "Germ warfare" for ulcerative colitis?

PMID- 11316189
TI  - Endoscopic removal of colonic lipomas.

PMID- 11316190
TI  - Re: Liu et al.--Estrogen receptor status in inoperable hepatocellular carcinoma.

PMID- 11316191
TI  - Diagnosis of Helicobacter pylori infection with a stool assay: is it useful after
      eradication treatment?

PMID- 11316192
TI  - Subsequent loss of the proliferated bile ductules in fulminant hepatitis in
      childhood--isn't it caused by apoptosis?

PMID- 11316193
TI  - Cataflam-induced esophageal ulceration.

PMID- 11316194
TI  - Thrombotic complications in inflammatory bowel disease: a multifactorial
      etiology.

PMID- 11316195
TI  - Endosonographic features of Brunner's gland hamartoma: location within the fourth
      echolayer?

PMID- 11316196
TI  - Dry cough and optic neuritis: two rare complications of interferon alpha
      treatment in chronic viral hepatitis.

PMID- 11316197
TI  - Transmission of hepatitis C through tattooing in a United States prison.

PMID- 11316198
TI  - Treatment of severe esophageal Crohn's disease with thalidomide.

PMID- 11316199
TI  - Exacerbation of inflammatory bowel disease associated with use of celecoxib.

PMID- 11316200
TI  - Therapeutic experience of hyperbaric oxygenation in entero-Behcet syndrome.

PMID- 11316201
TI  - A contented colon.

PMID- 11316202
TI  - Percutaneous endoscopic gastrostomy and stomal bilious leakage--another
      management option?

PMID- 11316203
TI  - Hepatic failure and encephalopathy attributed to an interaction between
      acetaminophen and rifampicin.

PMID- 11316204
TI  - Angioedema after interferon therapy for chronic hepatitis C.

PMID- 11316205
TI  - Pylephlebitis--diagnosis and management.

PMID- 11316206
TI  - Human pituitary tumor transforming gene 1 (hPTTG1) in gastric mucosal tissues.

PMID- 11316207
TI  - How important are the disturbances of lower gastrointestinal bowel habits in
      diabetic outpatients?

PMID- 11316208
TI  - Is irritable bowel syndrome more than just a gastroenterologist's problem?

PMID- 11316209
TI  - "I think you have pancreatic cancer but I can't prove it yet".

PMID- 11316210
TI  - Colonoscopic gamble.

PMID- 11316211
TI  - Medical-legal risks of incident cancers after clearing colonoscopy.
AB  - Colonoscopy and polypectomy effectively reduce the incidence and mortality of
      colorectal cancer, but some patients present with fully developed cancers within
      1-4 yr of a colonoscopy that apparently cleared the colon of neoplasia. These
      events may result in medical-legal action against colonoscopists, generally based
      on an assumption of negligent technical performance of the procedure. Alternative
      explanations for the development of interval cancers include variable growth
      rates of colorectal cancers, the inherent miss rate of the procedure even when
      optimal examination techniques are used, and the possibility of flat lesions that
      are not readily detected by standard colonoscopic techniques. This paper
      discusses issues relevant to reduction of medical-legal risks associated with
      interval cancers after clearing colonoscopy. These issues include informed
      consent, documentation of cecal intubation, appropriate description of
      preparation, documentation of examination time and technique, and attention to
      potential atypical neoplasms.

PMID- 11316212
TI  - A critical approach to noncardiac chest pain: pathophysiology, diagnosis, and
      treatment.
AB  - Approximately 30% of coronary angiograms performed in this country are negative
      for significant coronary artery disease. These patients are classified as having
      noncardiac or unexplained chest pain (UCP). Despite the good overall prognosis,
      this condition has significant morbidity and costs. The pathophysiology of this
      condition is likely caused by overlapping cardiac, esophageal, and psychiatric
      abnormalities with visceral hyperalgesia playing a central role.
      Gastroenterologists are often consulted in the evaluation of these patients
      because esophageal disorders are among the most common conditions associated with
      UCP. However, clinical symptoms are unreliable in differentiating between
      esophageal and cardiac causes of UCP. Gastroesophageal reflux disease, not
      esophageal motility disorders, is the most common esophageal disorder present in
      patients with UCP. The most useful diagnostic test in the evaluation of UCP is 24
      h pH monitoring. An initial empiric trial of high-dose acid suppression is the
      most cost-effective intervention in the management of these patients. A clinical
      algorithm is suggested for the evaluation and treatment of UCP.

PMID- 11316213
TI  - Stability of gastric secretory inhibition during 6-month treatment with
      omeprazole in patients with gastroesophageal reflux disease.
AB  - OBJECTIVE: A trend toward relapse of reflux symptoms and esophagitis during long
      term treatment with proton pump inhibitors has been reported. The purpose of this
      study was to evaluate the existence of tachyphylaxia to the effect of proton pump
      inhibitors on gastric acidity and gastroesophageal reflux over time. METHODS: A
      total of 23 patients with reflux esophagitis underwent 24-h intragastric and
      intraesophageal pH-metry after 7, 90, and 180 days of continued dosing with 20 mg
      of omeprazole once daily before breakfast. RESULTS: The total median percentages
      of time gastric pH <4 (interquartile range) were 49% (35-70%), 60% (36-76%), and
      42% (26-66%) after 7, 90, and 180 days (p = 0.14). Percentages of time gastric pH
      <3 were 41%, 54%, and 34%, respectively (p = 0.19). The median percentages of
      total time esophageal pH <4 were 1.1%, 2.5%, and 1.1%, respectively (p = 0.70).
      Healing of esophagitis was achieved in 84% of the patients after 6 months.
      Heartburn improved in six, worsened in three, and was unchanged in 10 patients (p
      = 0.16). There was no statistical significant relationship between change in
      esophageal acid exposure and change in severity of heartburn. CONCLUSIONS: A dose
      of 20 mg of omeprazole once daily consistently controlled patients' symptoms and
      kept gastric acidity at a stable level over a period of 6 months. There is no
      evidence of diminution in the effects of 20 mg of omeprazole over time that could
      indicate the development of tolerance.

PMID- 11316214
TI  - Esophageal pH monitoring: are you sure that the electrode is properly placed?
AB  - OBJECTIVE: A crucial methodological aspect of ambulatory 24-h esophageal pH
      monitoring is electrode placement. Lower esophageal sphincter (LES) location is
      recommended for standard electrode positioning. The aim of the present study was
      to evaluate prospectively whether LES manometric location and intragastric pH
      acid confirmation suffice to guarantee that the pH electrode is properly placed.
      METHODS: We evaluated data from 402 consecutive patients undergoing esophageal pH
      monitoring. LES location was determined by manometry, and the pH electrode was
      introduced until a pH recording <3 was obtained. Subsequently, it was positioned
      5 cm above the proximal LES border. Thereafter, adequate catheter placement and
      absence of bends or loops were checked by fluoroscopy. Patients with bent or
      rolled catheters were instructed to have breakfast immediately, and catheter
      placement was checked again by fluoroscopy. RESULTS: When checked by fluoroscopy,
      the catheter was properly placed in 383 patients (95.3%). In the other 19 (4.7%),
      it was not located in the distal part of the esophagus owing to bending or
      rolling: 14 in the esophagus and five in the pharynx. After breakfast, 14 of the
      19 malpositioned catheters were properly positioned whereas five remained bent or
      rolled. Those bent in the esophagus were more prone to unbending (12 of 14) than
      those bent or rolled in the pharynx (two of five). CONCLUSIONS: After LES
      location by manometry and demonstration of acid pH during the pH step-up
      technique, the pH electrode was properly placed in more than 95% of cases.
      Nevertheless, it cannot be completely guaranteed that the pH catheter will not
      bend or roll, and the pH electrode will not be malpositioned. Eating immediately
      after electrode placement resolves this problem in the majority (75%) of cases.
      Therefore, we recommend that patients undergoing esophageal pH-metric studies be
      instructed to eat as soon as possible after electrode placement to minimize these
      possible pitfalls.

PMID- 11316215
TI  - Lansoprazole treatment of patients with chronic idiopathic laryngitis: a placebo
      controlled trial.
AB  - OBJECTIVE: Previous uncontrolled studies suggested a therapeutic benefit for
      treating gastroesophageal reflux disease (GERD) among patients with laryngitis.
      The present study is the first randomized, placebo-controlled, double-blind study
      of gastric acid suppression among patients with laryngitis in the United States.
      METHODS: Patients diagnosed with idiopathic chronic laryngitis were randomized to
      receive either lansoprazole 30 mg p.o. b.i.d. or a matching placebo for 3 months.
      Before randomization, all patients underwent upper endoscopy, dual probe
      ambulatory 24-h esophageal pH-metry, and laryngoscopy, as well as completing a
      symptom questionnaire for GERD and laryngitis. The primary outcome of treatment
      was the complete resolution of laryngeal symptoms. RESULTS: A total of 22
      patients with symptoms and signs of chronic laryngitis were enrolled, 20 of whom
      completed the study. At baseline, there were no significant differences between
      the two groups with regards to GERD symptoms, erosive esophagitis, proximal and
      distal esophageal pH-metry, or laryngeal signs and symptoms. In an intention-to
      treat analysis, six patients in the lansoprazole group (50%) and only one patient
      (10%) in the placebo group achieved a complete symptomatic response, p = 0.04.
      Apart from receiving lansoprazole, there were no significant differences between
      responders and nonresponders in any of baseline esophageal or laryngeal signs and
      symptoms. CONCLUSIONS: Empirical treatment with lansoprazole is efficacious in
      relieving symptoms of laryngitis compared to placebo. Such treatment can be
      considered as a first-line option in managing patients with idiopathic chronic
      laryngitis.

PMID- 11316216
TI  - The ringed esophagus: histological features of GERD.
AB  - OBJECTIVE: The "ringed" or "corrugated" esophagus is a cause of chronic dysphagia
      and recurrent food impactions in young men. It was previously believed to be a
      congenital condition, but recent case series have documented histological
      esophagitis in these patients. We have treated 19 patients with a ringed
      esophagus and are impressed that this represents an acquired condition with
      gastroesophageal reflux disease (GERD) as its etiology. Our goals are to present
      the largest case series to date of ringed esophagus, discuss the evidence for
      GERD, and suggest a strategy for its diagnosis and management. METHODS: The
      charts of 19 patients with a ringed esophagus were reviewed. A single pathologist
      interpreted all available esophageal biopsy specimens and graded them for the
      presence of GERD-related abnormalities. Phone interviews were conducted to assess
      response to therapy and confirm historical features obtained from medical
      records. RESULTS: The typical patient is a young man (median age 35, M:F 17:2)
      with long-standing dysphagia and multiple food impactions. Endoscopy revealed
      multiple concentric rings that persisted despite air insufflation and caused
      significant stenosis. Of the 11 patients with available histology, all had basal
      cell hyperplasia, papillomatosis, and an increased number of intraepithelial
      eosinophils. Other clinical features of GERD such as heartburn, endoscopic
      esophagitis, and hiatal hernia were often absent. Response to dilation and acid
      suppression was good. CONCLUSIONS: The uniform presence of histological
      esophagitis with intraepithelial eosinophils, basal cell hyperplasia, and
      papillary lengthening strongly implicates GERD in the pathogenesis of the adult
      ringed esophagus. In addition to a series of gradual esophageal dilations, we
      suggest using a proton pump inhibitor to provide acid suppression.

PMID- 11316217
TI  - Cyclooxygenase-2 expression in the Barrett's metaplasia-dysplasia-adenocarcinoma
      sequence.
AB  - OBJECTIVE: Increased expression of the inducible cyclooxygenase 2 (COX-2) enzyme
      has been detected in esophageal and colonic adenocarcinoma, and intake of aspirin
      and non-steroidal anti-inflammatory drugs, known COX-2 inhibitors, have been
      associated with reduced tumor formation. Elevated COX-2 mRNA but variable protein
      expression has been demonstrated in Barrett's epithelium, and we have, therefore,
      sought to evaluate the expression of COX-2 protein throughout the Barrett's
      metaplasia-dysplasia-adenocarcinoma sequence. METHODS: Paraffin-embedded
      esophageal biopsies from 56 different patients with Barrett's esophagus were
      analyzed for COX-2 expression by immunohistochemistry. Twenty contained
      nondysplastic intestinal and gastric metaplasia, 12 demonstrated low-grade
      dysplasia (LGD), 12 high-grade dysplasia (HGD), and 12 contained invasive
      adenocarcinoma. RESULTS: Epithelial expression of COX-2 protein was detected in
      75% (15/20) of benign cases, 83% (10/12) of cases with LGD, and 100% of cases
      with HGD or adenocarcinoma. Using a semiquantitative analysis, median staining
      scores for the groups were 2, 3, 14, and 13, respectively (scale 0-16), with the
      expression being significantly higher in the HGD and cancer groups compared to
      benign and LGD groups (p < 0.001). CONCLUSIONS: This study demonstrates clear COX
      2 expression in the epithelial cells in Barrett's metaplasia, confirms elevated
      expression in adenocarcinoma, and shows that the elevation in expression occurs
      in the progression from LGD to HGD.

PMID- 11316218
TI  - Effect of small intestinal nutrient infusion on appetite, gastrointestinal
      hormone release, and gastric myoelectrical activity in young and older men.
AB  - OBJECTIVE: The mechanisms responsible for the reduction in appetite and slowing
      of gastric emptying in older persons are poorly understood. The aim of this study
      was to evaluate the effects of aging on small intestinal regulation of appetite,
      GI hormone release, and gastric myoelectrical activity. METHODS: Thirteen older
      (65-84 yr) and 13 young (18-32 yr) healthy men received isovolumetric,
      intraduodenal (i.d.) infusions of saline (control), lipid, and glucose for 120
      min, on separate days. The energy content of the lipid and glucose infusions was
      identical at 2.86 kcal/min. Immediately after the i.d. infusions, each subject
      was offered a buffet meal, and ad libitum food intake was quantified. Blood
      glucose and plasma insulin, glucagon-like peptide 1, and glucose-dependent
      insulinotropic peptide were measured. Gastric myoelectrical activity was measured
      by surface electrogastrography (EGG). RESULTS: I.d. lipid suppressed food intake
      in both the young and older men (p < 0.05), whereas i.d. glucose suppressed food
      intake only in the older men (p < 0.05). The blood glucose (p < 0.01) and insulin
      (p < 0.05) responses to i.d. glucose were greater in older than young men.
      However, there were no differences in glucagon-like peptide 1 or glucose
      dependent insulinotropic peptide responses to any of the infusions. There was a
      greater increase in the EGG power ratio both during and after i.d. glucose
      infusion in the young (p < 0.05) than the older men, and an attenuation of EGG
      frequency by nutrient infusions in older, but not young, men. CONCLUSIONS: Our
      findings indicate that aging is associated with nutrient-specific changes in
      appetite, hormonal, and gastric myoelectrical (EGG) responses to i.d. nutrients.
      An enhanced satiating effect of small intestinal carbohydrates may potentially
      contribute to the anorexia of aging.

PMID- 11316219
TI  - Person X situation interactionism in self-encoding (I am...when...): implications
      for affect regulation and social information processing.
AB  - Although Person X Situation (P X S) interactionism is central in current social
      cognitive conceptions of personality organization, its implications for the
      encoding of the self remain unexplored. Two studies examined the causal role of P
      X S interactionism in self-encoding on affect regulation and discriminative
      social perception. Following failure (Studies 1 and 2) and success (Study 2)
      ideation, participants were prompted to encode the self either in P X S
      interactionist terms (I am...when...) or in traitlike unconditional terms (I
      am...). Interactionist (compared with unconditional) self-encoding led to less
      affective extremity, suggesting that such encoding may prevent individuals from
      generalizing specific success and failure experiences to the self as a whole.
      Study 2 also found that interactionist self-encoding attenuated the endorsement
      of global stereotypes, suggesting that such encoding may enhance fine-grained
      social perception as well.

PMID- 11316220
TI  - Do situational expectations produce situational inferenes? The role of future
      expectations in directing inferential goals.
AB  - Little is known about the conditions that lead observers to adopt different
      inferential goals in the context of their everyday lives. Four studies examined
      whether future expectations created situational inferential goals. In 2
      quasiexperimental studies, students made more situational inferences for targets
      in their expected future careers. In 2 experiments, situational expectations were
      manipulated, and participants made more situational inferences when they expected
      to be in the same situation as the target. This tendency was stronger when
      observers devoted minimal cognitive effort to their inferences, suggesting that
      when observers have situational expectations, making situational inferences is
      less effortful than making dispositional inferences.

PMID- 11316221
TI  - Confirmation bias in sequential information search after preliminary decisions:
      an expansion of dissonance theoretical research on selective exposure to
      information.
AB  - Research on selective exposure to information consistently shows that, after
      having made a decision, people prefer supporting over conflicting information.
      However, in all of these experiments participants were given an overview of all
      available pieces of information, selected them simultaneously, and did not
      process the requested information during the selection phase. In the present
      research the authors show that an even stronger preference for supporting
      information arises if information is presented and processed sequentially instead
      of simultaneously (Experiment 1), and they demonstrate that this stronger
      confirmation bias is due to sequential presentation and not to sequential
      processing of information (Experiment 2). The authors provide evidence that the
      increase in confirmation bias under sequential presentation is caused by
      heightened commitment due to the participants' increased focusing on their
      decision (Experiments 3 and 4).

PMID- 11316222
TI  - From chump to champ: people's appraisals of their earlier and present selves.
AB  - The authors present and test a theory of temporal self-appraisal. According to
      the theory, people can maintain their typically favorable self-regard by
      disparaging their distant and complimenting their recent past selves. This
      pattern of appraisals should be stronger for more important attributes because of
      their greater impact on self-regard and stronger for self-ratings than for
      ratings of other people. Studies 1 and 2 demonstrated that participants are more
      critical of distant past selves than of current selves, and Study 3 showed that
      this effect is obtained even when concurrent evaluations indicate no actual
      improvement. Studies 4 and 5 revealed that people perceived greater improvement
      for self than for acquaintances and siblings over the same time period. Study 6
      provided support for the predicted effects of temporal distance and attribute
      importance on people's evaluation of past selves.

PMID- 11316223
TI  - The personality of familiar and significant people: the lay perceiver as a social
      cognitive theorist.
AB  - When are perceivers guided more by implicit social-cognitive theories of
      personality and when more by trait theories? As perceivers become more familiar
      with a person they infer relatively more psychological mediating variables (e.g.,
      construals, goals) that underlie the person's behavior and relatively fewer
      broad, uncontextualized traits such as aggressive or friendly (Study 1). The
      effects of familiarity are moderated by the importance of the target to
      perceivers (Study 2). Specifically, perceivers make relatively more inferences
      using mediating variables and fewer inferences with traits as the target becomes
      more familiar, if and only if the target plays an important role in their lives.
      The findings indicate that psychological mediating variables play a significant
      role in lay perceptions of people and specify conditions in which perceiver's
      function like implicit social-cognitive theorists, namely, when the perceived is
      familiar and important to the perceiver.

PMID- 11316224
TI  - Perceptual asymmetry in consensus estimates of majority and minority members.
AB  - Three experiments revealed a consistent pattern of consensus estimates. Numerical
      status and group growth or decline were manipulated between subjects. Growth was
      manipulated orthogonally to a 3rd variable: focus. Focus was manipulated by
      describing growth information with respect either to the in-group or the out
      group (e.g., in-group growth and out-group decline). A Numerical Status X Focus
      interaction emerged in Study 1. Numerical minority members' consensus estimates
      for an opinion issue increased when growth information was out-group focused,
      whereas majority members' estimates did not differ as a function of the focus
      variable. Study 2 replicated these effects across other opinion dimensions. Study
      3 confirmed the importance of the growth and focus variables in the absence of
      numerical status manipulations.

PMID- 11316225
TI  - Global and specific relational models in the experience of social interactions.
AB  - Two studies demonstrated that global and relationship-specific models of self and
      other are correlated but not redundant constructs. Relationship-specific models
      were operationalized in terms of significant role relationships (Study 1) and
      salient relationships (i.e., frequent interactions; Study 2). Longitudinal
      analyses (Study 1) suggested that specific models generalized to global ones over
      time and that global models had a small but significant effect in shaping
      specific models over time. Through an event-sampling method, Study 2 assessed the
      quality and intimacy of daily interactions over a 7-day period. In hierarchical
      linear modeling analyses, both global and specific relational models explained
      the experience of daily interactions within relationships. This research
      highlighted that relational or attachment models can be considered global and
      specific representational structures, reflecting relational and individual
      differences.

PMID- 11316226
TI  - When groups are more competitive than individuals: the domain of the
      discontinuity effect.
AB  - The related goals of the research were to delineate the domain of discontinuity,
      1st by demonstrating its occurrence in a nonmatrix situation and, 2nd, by
      establishing the antecedent outcome conditions necessary for producing a
      discontinuity effect. The 1st goal was met by designing a mixed motive situation
      involving the production of origami products. Under these conditions, the
      magnitude of the discontinuity effect did not significantly differ from that in a
      matrix-only condition. The 2nd goal was met by a separate experiment that used H.
      H. Kelley and J. W. Thibaut's (1978) analysis of degree of noncorrespondence of
      outcomes. This experiment demonstrated that as noncorrespondence increased, so
      did the rate of competitive responding by groups but not by individuals. This
      pattern was qualified by an interaction with gender such that competitiveness was
      more markedly affected by noncorrespondence for groups of women than for groups
      of men.

PMID- 11316227
TI  - Perceived consensus influences intergroup behavior and stereotype accessibility.
AB  - Past research has demonstrated the powerful influence other people have on the
      thoughts and behaviors of individuals. However, the study of intergroup attitudes
      has focused primarily on the influence of direct exposure to out-group members as
      determinants of stereotypes and prejudice. Two experiments tested the hypothesis
      that learning that others share one's intergroup beliefs influences intergroup
      attitudes and behavior as well as stereotype representation. Experiment 1
      demonstrated that learning that one's beliefs are shared or not shared with
      others influences attitudes, behavior, and the strength of the attitude-behavior
      relationship. Experiment 2 demonstrated a potential mechanism for such effects by
      showing that learning about whether others share one's stereotypes influences the
      accessibility of those stereotypes and related stereotypes.

PMID- 11316228
TI  - Genetic and environmental influences on observed personality: evidence from the
      German Observational Study of Adult Twins.
AB  - Previous behavior-genetic research on adult personality relied primarily on self
      reports or peer reports that may be subject to contrast effects, resulting in
      biased estimates of genetic and environmental influences. In the German
      Observational Study of Adult Twins (GOSAT), personality traits of 168 monozygotic
      (MZ) and 132 dizygotic (DZ) twin pairs were rated on 35 adjective scales, largely
      markers of the Big 5. The ratings were provided by 120 judges who never met the
      twins but observed videotaped behaviors of 1 twin of each pair in 1 of 15
      different settings. The aggregated video-based trait ratings were highly
      reliable, and substantial correlations were obtained between MZ as well as DZ
      twins. Model-fit analyses suggested about 40% genetic, 25% shared environmental,
      and 35% nonshared environmental influence. Extraversion was the only trait that
      seemed not to be influenced by shared environment.

PMID- 11316229
TI  - What's in a name: implicit self-esteem and the automatic self.
AB  - This article explores the links between implicit self-esteem and the automatic
      self (D. L. Paulhus, 1993). Across 4 studies, name letter evaluations were
      positively biased, confirming that implicit self-esteem is generally positive (A.
      G. Greenwald & M. R. Banaji, 1995). Study 1 found that this name letter bias was
      stable over a 4-week period. Study 2 found that positive bias for name letters
      and positive bias for birth date numbers were correlated and that both biases
      became inhibited when participants were induced to respond in a deliberative
      manner. Studies 3-4 found that implicit self-evaluations corresponded with self
      reported self-evaluations, but only when participants were evaluating themselves
      very quickly (Study 3) or under cognitive load (Study 4). Together, these
      findings support the notion that implicit self-esteem phenomena are driven by
      self-evaluations that are activated automatically and without conscious self
      reflection.

PMID- 11316230
TI  - Modularity, evolution, and the binding problem: a view from stability theory.
AB  - Any biological object, and specifically the brain, is the result of evolution.
      Evolution proceeds by accumulation and combination of stable intermediate states
      as is well known, survival of the fittest really means survival of the stable.
      Simple examples abound: for instance, human emotional response involves both a
      fast archaic loop bypassing the cortex, and a slower cortical loop; motion
      control architecture in vertebrates is believed to involve combinations of simple
      motor primitives. However, in themselves, accumulations and combinations of
      stable elements have no reason to be stable. Hence the hypothesis that evolution
      will favor a particular form of stability, which automatically guarantees
      stability in combination. Such a form of stability, which we refer to as
      'contraction,' can be characterized mathematically. Thus, contraction theory may
      help guide functional modeling of the central nervous system, and conversely it
      provides a systematic method to build arbitrarily complex robots out of simpler
      elements. Furthermore, contraction theory may shed light on the problem of
      perceptual unity (binding problem) by providing simple models and conditions for
      the overall convergence of a large number of specialized processing elements
      connected through networks of feedback loops.

PMID- 11316231
TI  - A pruning method for the recursive least squared algorithm.
AB  - The recursive least squared (RLS) algorithm is an effective online training
      method for neural networks. However, its conjunctions with weight decay and
      pruning have not been well studied. This paper elucidates how generalization
      ability can be improved by selecting an appropriate initial value of the error
      covariance matrix in the RLS algorithm. Moreover, how the pruning of neural
      networks can be benefited by using the final value of the error covariance matrix
      will also be investigated. Our study found that the RLS algorithm is implicitly a
      weight decay method, where the weight decay effect is controlled by the initial
      value of the error covariance matrix; and that the inverse of the error
      covariance matrix is approximately equal to the Hessian matrix of the network
      being trained. We propose that neural networks are first trained by the RLS
      algorithm and then some unimportant weights are removed based on the approximate
      Hessian matrix. Simulation results show that our approach is an effective
      training and pruning method for neural networks.

PMID- 11316232
TI  - Two methods for encoding clusters.
AB  - This paper presents two methods for generating numerical codes representing
      clusters of Rn, while preserving various topological properties of data spaces.
      This is useful for networks whose input, or eventually output, consists of
      unordered sets of points. The first method is the best one from a theoretical
      point of view, while the second one is more usable for large clusters in
      practice.

PMID- 11316233
TI  - Numerical solution of differential equations using multiquadric radial basis
      functions networks.
AB  - This paper presents mesh-free procedures for solving linear differential
      equations (ODEs and elliptic PDEs) based on multiquadric (MQ) radial basis
      function networks (RBFNs). Based on our study of approximation of function and
      its derivatives using RBFNs that was reported in an earlier paper (Mai-Duy, N. &
      Tran-Cong, T. (1999). Approximation of function and its derivatives using radial
      basis function networks. Neural networks, submitted), new RBFN approximation
      procedures are developed in this paper for solving DEs, which can also be
      classified into two types: a direct (DRBFN) and an indirect (IRBFN) RBFN
      procedure. In the present procedures, the width of the RBFs is the only
      adjustable parameter according to a(i) = betad(i), where d(i) is the distance
      from the ith centre to the nearest centre. The IRBFN method is more accurate than
      the DRBFN one and experience so far shows that beta can be chosen in the range 7
      < or = beta 10 for the former. Different combinations of RBF centres and
      collocation points (uniformly and randomly distributed) are tested on both
      regularly and irregularly shaped domains. The results for a 1D Poisson's equation
      show that the DRBFN and the IRBFN procedures achieve a norm of error of at least
      O(1.0 x 10(-4)) and O(1.0 x 10(-8)), respectively, with a centre density of 50.
      Similarly, the results for a 2D Poisson's equation show that the DRBFN and the
      IRBFN procedures achieve a norm of error of at least O(1.0 x 10(-3)) and O(1.0
      x10(-6)) respectively, with a centre density of 12 X 12.

PMID- 11316234
TI  - Biomimetic gaze stabilization based on feedback-error-learning with nonparametric
      regression networks.
AB  - Oculomotor control in a humanoid robot faces similar problems as biological
      oculomotor systems, i.e. the stabilization of gaze in face of unknown
      perturbations of the body, selective attention, stereo vision, and dealing with
      large information processing delays. Given the nonlinearities of the geometry of
      binocular vision as well as the possible nonlinearities of the oculomotor plant,
      it is desirable to accomplish accurate control of these behaviors through
      learning approaches. This paper develops a learning control system for the
      phylogenetically oldest behaviors of oculomotor control, the stabilization
      reflexes of gaze. In a step-wise procedure, we demonstrate how control theoretic
      reasonable choices of control components result in an oculomotor control system
      that resembles the known functional anatomy of the primate oculomotor system. The
      core of the learning system is derived from the biologically inspired principle
      of feedback-error learning combined with a state-of-the-art non-parametric
      statistical learning network. With this circuitry, we demonstrate that our
      humanoid robot is able to acquire high performance visual stabilization reflexes
      after about 40 s of learning despite significant nonlinearities and processing
      delays in the system.

PMID- 11316235
TI  - A globally convergent Lagrange and barrier function iterative algorithm for the
      traveling salesman problem.
AB  - In this paper a globally convergent Lagrange and barrier function iterative
      algorithm is proposed for approximating a solution of the traveling salesman
      problem. The algorithm employs an entropy-type barrier function to deal with
      nonnegativity constraints and Lagrange multipliers to handle linear equality
      constraints, and attempts to produce a solution of high quality by generating a
      minimum point of a barrier problem for a sequence of descending values of the
      barrier parameter. For any given value of the barrier parameter, the algorithm
      searches for a minimum point of the barrier problem in a feasible descent
      direction, which has a desired property that the nonnegativity constraints are
      always satisfied automatically if the step length is a number between zero and
      one. At each iteration the feasible descent direction is found by updating
      Lagrange multipliers with a globally convergent iterative procedure. For any
      given value of the barrier parameter, the algorithm converges to a stationary
      point of the barrier problem without any condition on the objective function.
      Theoretical and numerical results show that the algorithm seems more effective
      and efficient than the softassign algorithm.

PMID- 11316236
TI  - Quick fuzzy backpropagation algorithm.
AB  - A modification of the fuzzy backpropagation (FBP) algorithm called QuickFBP
      algorithm is proposed, where the computation of the net function is significantly
      quicker. It is proved that the FBP algorithm is of exponential time complexity,
      while the QuickFBP algorithm is of polynomial time complexity. Convergence
      conditions of the QuickFBP, resp. the FBP algorithm are defined and proved for:
      (1) single output neural networks in case of training patterns with different
      targets; and (2) multiple output neural networks in case of training patterns
      with equivalued target vector. They support the automation of the weights
      training process (quasi-unsupervised learning) establishing the target value(s)
      depending on the network's input values. In these cases the simulation results
      confirm the convergence of both algorithms. An example with a large-sized neural
      network illustrates the significantly greater training speed of the QuickFBP
      rather than the FBP algorithm. The adaptation of an interactive web system to
      users on the basis of the QuickFBP algorithm is presented. Since the QuickFBP
      algorithm ensures quasi-unsupervised learning, this implies its broad
      applicability in areas of adaptive and adaptable interactive systems, data
      mining, etc. applications.

PMID- 11316237
TI  - Regulation of in situ complement activation via the lectin pathway in patients
      with IgA nephropathy.
AB  - The lectin pathway, which is initiated by mannose-binding lectin (MBL) and MBL
      associated serine protease (MASP), is one of the possible routes to activate the
      complement cascade in immunoglobulin A (IgA) nephropathy. The purpose of this
      study was to elucidate the regulatory mechanism of the pathway. Levels of
      complement activation products and regulatory proteins were measured in sera from
      27 patients with IgA nephropathy, and generation of fluid-phase complement
      activation products in the presence of pooled normal human serum was quantified
      to evaluate activation in vitro. Although there were no significant differences
      in the serum levels and in vitro activation between the MBL-MASP positive (n =
      14) and negative (n = 13) groups, there were positive correlations between
      complement activation products (Bb fragment and C4d fragment) and regulatory
      proteins (factor H, C4-binding protein, and C1 inhibitor) in the MBL-MASP
      positive group. Furthermore, immunohistochemical studies demonstrated glomerular
      deposition of the regulatory protein (C4-binding protein, alpha2-macroglobulin,
      and factor H) in all patients in the MBL-MASP-positive group. These findings
      suggest that the regulatory proteins control in situ complement activation via
      the lectin pathway immediately, and continuous activation due to inadequate
      control will lead to the advanced glomerular injury.

PMID- 11316238
TI  - Corticosteroid therapy in patients with IgA nephropathy and impaired renal
      function.
AB  - AIM: IgA nephropathy (IgAN) is a common type of primary glomerulonephritis that
      constitutes a major cause of end-stage renal disease. Oral and/or intravenous
      glucocorticoid therapy can protect against progression of IgAN in patients with
      preserved renal function. We evaluated steroid therapy in IgAN with established
      renal dysfunction. PATIENTS AND METHODS: We retrospectively analyzed the effect
      of methylprednisolone (MP) pulse therapy in 8 IgAN patients with serum creatinine
      concentrations (sCr) 2.76 +/- 1.32 mg/dl (mean +/- SD). In each patient renal
      function had progressively deteriorated in the 12 months preceding treatment, as
      indicated by negative slopes of 1/sCr plotted against time (regression
      coefficients). RESULTS: Regression coefficients during the 12 months following
      therapy improved significantly from -0.02333 +/- 0.00732 to -0.00036 +/- 0.00423
      dl/mg/month, respectively. The mean difference in slope was 0.0230 +/- 0.0076
      dl/mg/month (95% confidence interval, 0.0165 to 0.0295, p < 0.001). Proteinuria
      also significantly decreased from a mean urine protein/creatinine ratio of 2.57
      +/- 1.12 before therapy to 1.12 +/- 0.84 6 months after therapy (p < 0.005).
      Other factors that might affect progression of renal dysfunction remained
      unchanged during the observation periods. CONCLUSION: Corticosteroids may
      attenuate progression of renal failure and delay the need for dialysis in this
      patient population, although a large randomized trial is necessary.

PMID- 11316239
TI  - Do patients with obstructive sleep apnea have clinically significant proteinuria?
AB  - AIM: Previous studies report a high prevalence of proteinuria in patients with
      obstructive sleep apnea syndrome (OSAS). This common syndrome may therefore be an
      important cause ofproteinuria and renal failure in the general population. This
      study was undertaken to assess the prevalence of proteinuria among OSAS patients,
      and to identify the factors associated with urine protein excretion in these
      patients. METHODS: Overnight polysomnography, urine protein to creatinine ratio
      (PTCR), body mass index (BMI), mean arterial pressure (MAP), and hematocrit were
      assessed prospectively in 224 patients referred for evaluation of suspected OSAS.
      Sleep apnea was defined as apnea-hypopnea score (AHS) > or = 5 events/hour.
      Proteinuria was defined as PTCR > 0.2 mg/mg. RESULTS: Sleep apnea was present in
      143 subjects (63.8%), and proteinuria in 10 (4.5%). The highest PTCR was 0.677
      mg/mg. PTCR and AHS were weakly correlated (r = 0.12, p = 0.08). PTCR correlated
      (alpha = 0.05) with lowest oxygen saturation (r = -0.18, p = < 0.01), time spent
      with oxygen saturation below 90% (r = 0.19, p = < 0.01), and BMI (r= 0. 17, p = <
      0.01). The mean PTCR was similar in subjects with and without sleep apnea.
      Proteinuria was present in 7 of 143 (4.9%) subjects with AHS > or = 5 and 3 of 81
      (3.7%) subjects with AHS < 5, a relative risk of 1.34, 95% CI (0.34, 5.32).
      Predictors of LogPTCR in multiple linear regression (model R2 - 0.104) were: AHS
      (< 5 or > or = 5), baseline oxygen saturation, sex, and MAP. CONCLUSIONS:
      Clinically significant proteinuria is uncommon in OSAS. The prevalence and
      severity of proteinuria are similar in both OSAS patients and patients without
      sleep-disordered breathing. Sleep apnea severity is weakly associated with urine
      protein excretion, related more to hypoxemia than to frequency of apneic events.

PMID- 11316240
TI  - An evaluation of the physicochemical risk for renal stone disease during
      pregnancy.
AB  - Seventeen subjects were studied during the third trimester of pregnancy (PG) and
      post partum (NPG) to evaluate the effect of pregnancy on the physicochemical risk
      of renal stone disease. Levels of urinary saturation for calcium oxalate (CaOx),
      brushite (Br), uric acid (UA), and monosodium urate (NaU) were determined as well
      as urinary excretions of stone-forming elements. In addition to urinary calcium
      excretion, assessment of calcium metabolism included serum calcium and
      parathyroid hormone. Urinary calcium excretion was 251 +/- 127 mg/day during
      pregnancy and 121 +/- 67 mg/day post partum (p < 0.001). This was associated with
      a higher intake of dietary calcium and altered renal handling of calcium with an
      increase in the filtered load and a decrease in renal tubular reabsorption. The
      increase in urinary calcium resulted in a higher level of saturation of the urine
      for calcium oxalate (NPG 2.1 +/- 1.0 vs PG 3.0 +/- 1.1, p < 0.02) and brushite
      (NPG 1.2 +/- 0.9 vs PG 1.9 +/- 1.1, p < 0.05) compatible with an increased risk
      of stone formation.

PMID- 11316241
TI  - The effect of i.v. iron alone or in combination with low-dose erythropoietin in
      the rapid correction of anemia of chronic renal failure in the predialysis
      period.
AB  - BACKGROUND: It is now more and more evident that anemia of predialysis chronic
      renal failure (CRF) should be actively treated, since long-standing anemia may
      cause irremediable damage to the heart. The most common form of treatment of this
      anemia is subcutaneous erythropoietin (EPO). iron (Fe) deficiency can also
      contribute to anemia in predialysis CRF, and intravenous iron (i.v. Fe) can
      frequently improve it. It is possible, therefore, that the combination of EPO and
      i.v. Fe may have an additive effect, and cause a rapid improvement in anemia with
      relatively small doses of EPO. PURPOSE: The purpose of this study was an initial
      study: to assess the ability of a combination of low-dose EPO and i.v. Fe, given
      weekly for 5 doses, to correct the anemia of predialysis CRF patients compared to
      the use of i.v. Fe alone in a randomized study. In the follow-up study: to assess
      the ability of the maintenance of adequate iron stores for one year to achieve
      and maintain the target Hct of 35% with the minimum dose of EPO. Initial study:
      METHOD: Ninety predialysis CRF patients (creatinine clearance 10-40 ml/min/1.73
      m2 received either: Group A (45 patients): 200 mg i.v. Fe as Fe sucrose (Venofer,
      Vifor Int.) once per week for 5 doses in combination with 2,000 international
      units (IU) EPO (Eprex, Cilag-Janssen), subcutaneously given simultaneously also
      for 5 doses. Group B (45 patients): the same dose of i.v. Fe as in Group A but
      without EPO. RESULTS: The mean increase in hematocrit (Hct) and hemoglobin (Hb)
      by one week after the last dose was greater in group A, 4.54 +/- 2.64% (p < 0.01)
      and 1.37 +/- 0.84 g% (p < 0.01), respectively, than in Group B, 2.74 +/- 2.72% (p
      < 0.05) and 0.91 +/- 0.78 g% (p < 0.05), respectively. 80% of those in Group A
      had an increase in Hct of 3 vol% or more compared to 48.9% in Group B (p < 0.01).
      40% of those in Group A reached the target Hct of 35% compared to 28.9% in Group
      B (p > 0.05). Follow-up study: During a 12-month follow-up period, enough i.v.
      iron was given to maintain the Hct at 35%, while keeping the serum ferritin at <
      400 ug/l and % Fe Sat at < 40%. If the i.v. Fe alone was not capable of
      maintaining the target Hct, EPO was given in increasing doses. Eighteen patients
      required dialysis. Of the 72 patients who did not require dialysis, 24 (33.3%)
      maintained the target Hct with i.v. Fe alone, without EPO. All the remaining 48
      patients (66.7%) continued to receive EPO in addition to the i.v. Fe, and 47
      achieved and maintained the target Hct with a mean EPO dose of 2,979 +/- 1,326
      IU/week. CONCLUSION: The combination of low-dose EPO and i.v. Fe had a rapid and
      additive effect on the correction of anemia in CRF predialysis patients.
      Maintaining adequate iron stores with i.v. Fe during a subsequent maintenance
      phase allowed the target Hct of 35% to be reached and maintained with low-dose
      EPO in two-thirds of the predialysis patients and with no EPO at all in one
      third.

PMID- 11316242
TI  - Interferon therapy in hemodialysis patients with chronic hepatitis C virus
      infection induces a high rate of long-term sustained virological and biochemical
      response.
AB  - AIM: The aim of the present study was to analyze the efficacy and tolerance of
      interferon (IFN) therapy in hemodialysis (HD) patients with chronic hepatitis C
      virus (HCV) infection. Specifically, we assessed whether the "normalization" of
      serum ALT levels was associated with the disappearance of the HCV-RNA. METHODS:
      Thirteen hemodialysis patients with chronic hepatitis C were treated for one year
      with 3 MU of alpha-IFN. The primary end point was a sustained virological
      response defined as the absence of HCV-RNA in the last follow-up; the secondary
      end points were normalization of the serum ALT levels and histological
      improvement. ALT was considered "normal" below 27 IU/l. RESULTS: Ten patients
      completed the treatment, which was discontinued in the other 3 (23%). By the end
      of the treatment a virological response was observed in 8 of the 10 patients
      (80%) who completed the one-year IFN therapy. Biochemical response was associated
      with a virological response in 8 of the 9 patients in whom ALT levels became
      normal. Three patients had a biochemical and virological relapse in the follow
      up. Two of them received a further year of IFN therapy, which resulted in a
      sustained biochemical and virological response. In all patients who underwent a
      liver biopsy (n = 5), the inflammation score improved. After a median follow-up
      of 5 years (range 2 - 7), a sustained response was observed in 6 (46%) of the 13
      patients enrolled. Two patients with a sustained response received a kidney
      transplant and after more than 6 years still maintain a biochemical and
      virological response. Side effects included flu-like syndrome (n = 8), hemoglobin
      decrease (n = 8), thrombocytopenia (n = 3), depression (n = 1) and seizures (n =
      1). CONCLUSION: IFN treatment over a one-year period produces a high rate of long
      term virological response in HD patients, associated to a biochemical response in
      all cases.

PMID- 11316243
TI  - Morbidity and mortality during renal replacement therapy: dialysis versus
      transplantation.
AB  - AIM: Many patients with end-stage renal disease are eligible for renal
      transplantation. To enable a patient to choose between transplantation or to
      remain on dialysis comparable data on morbidity and mortality should be
      available. METHODS: Data were collected retrospectively from the medical records
      of all patients on the waiting list for renal transplantation and of transplanted
      patients during the period January 1, 1990, to January 1, 1997. All patients were
      dialyzed in the Kennemer Gasthuis and renal transplantation was performed in the
      Leiden University Medical Center (LUMC). Morbidity and mortality in both groups
      were compared. Morbidity was assessed by studying number, length and cause of
      hospital admissions. RESULTS: During the study period 102 patients had been on
      the waiting list and 54 patients had been transplanted in the LUMC. Mean length
      of stay on the waiting list before transplantation was 37 months. During the
      follow-up period 11 patients (10.8%) died on the waiting list and 6 patients
      (11.1%) died after renal transplantation. The mean length of stay on the waiting
      list of these two groups was much longer, being 55 months and 62 months,
      respectively. Length of hospitalization was significantly different between both
      patient groups during the first 6 months of treatment (13.24 days for those on
      the waiting list versus 40.75 days transplanted patients) and after 6 months
      (32.4 days for those on the waiting list versus 13.1 days transplanted patients).
      The number of hospital admissions did not differ significantly. Dialysis-related
      admissions constituted 47% of the total of admissions in the waiting list group
      and transplantation-related admissions were 43% in the transplanted group.
      CONCLUSION: In the present study we revealed no difference in overall mortality.
      However, mortality was influenced by length of stay on the waiting list.
      Morbidity was increased during the first 6 months after transplantation. Therapy
      modality greatly influenced the specific cause of morbidity.

PMID- 11316244
TI  - Mimicry of surreptitious diuretic ingestion and the ability to make a genetic
      diagnosis.
AB  - Gitelman's syndrome, also known as "hypocalciuric variant of Bartter's syndrome",
      is a cause of chronic hypokalemia and hypomagnesemia in adults. A specific gene
      has been found responsible for this disorder, encoding the thiazide-sensitive
      NaCl coporter (TSC) in the distal convoluted tubule. We describe a psychiatric
      patient with chronic symptomatic hypokalemia and hypomagnesemia whose electrolyte
      disturbances were subsequently misdiagnosed as an acute alcohol and
      benzodiazepine withdrawal syndrome, as chronic diuretic abuse and as a classical
      Bartter's syndrome. Finally, genetic investigation revealed the presence of
      mutations in the SLC12A3 gene leading to the proper diagnosis of Gitelman's
      syndrome. We emphasize that Gitelman's syndrome should be suspected in every
      hypokalemic patient with biochemical resemblance of diuretic ingestion,
      especially when repeated toxic screens for diuretics are negative. The ability to
      make a molecular-genetic diagnosis can be of practical benefit in confusing
      clinical settings.

PMID- 11316245
TI  - Heterogeneous expression of nonmuscle myosin heavy chain-B in mesangial cells of
      patients with Gitelman's syndrome.
AB  - AIMS: It has been suggested that angiotensin II (Ang II) promotes hypertrophy and
      hyperplasia of mesangial cells. Nonmuscle myosin heavy chain-B (NMHC-B) and alpha
      smooth muscle (SM) actin are considered to be molecular markers for phenotypic
      change ofproliferative mesangial cells. One of the clinical characteristics in
      Gitelman's syndrome (GS) is the elevation of plasma Ang II. However, little is
      known about the relation between Ang II and phenotypic change of mesangial cells
      in patients with GS. In this report, we examined the expression of NMHC-B and
      alpha-SM actin in mesangial cells of two GS patients. MATERIALS AND METHODS:
      Plasma renin activity, and the concentrations of Ang II, 6-keto-prostaglandin
      F1alpha (6-keto-PGF1alpha), urinary kallikrein, and 6-keto-PGF1alpha were
      measured. Immunohistochemical staining of NMHC-B and alpha-SM actin in mesangial
      cells of GS patients was also performed. RESULTS: Both cases of GS showed normal
      glomerular function, few histological abnormalities, and higher than normal
      plasma concentrations of renin and Ang II. Furthermore, one case showed a high
      urinary concentration of kallikrein and the expression of both NMHC-B and alpha
      SM actin in mesangial cells. The other case showed a high urinary concentration
      of 6-keto-PGF1alpha but not kallikrein and without the expression of NMHC-B and
      alpha-SM actin. CONCLUSION: Not only plasma kinin-kallikrein and prostaglandins,
      but the renal expression of NMHC-B and alpha-SM actin may be variable in
      different patients with GS.

PMID- 11316246
TI  - A missense mutation, A156T, in the alpha-galactosidase A gene causes typical
      Fabry disease.
AB  - AIMS: Fabry disease is a rare but important cause of end-stage renal disease.
      Recent molecular investigations on alpha-galactosidase A (alpha-Gal A) have
      proven the existence of atypical variants in Fabry disease, making genotype
      assessment of each phenotype indispensable. We report here a missense mutation,
      which causes a typical form of Fabry disease. MATERIAL AND METHODS: The proband,
      a 45-year-old man, presented with acroparesthesias, hypohidrosis, left
      ventricular hypertrophy, renal involvement (proteinuria and renal insufficiency)
      with typical microscopic findings and extremely reduced plasma alpha-Gal A
      activity, indicating the typical form of the disease. Total RNA was isolated from
      the proband's cultured fibroblasts, reverse-transcribed and amplified for direct
      sequencing of alpha-Gal A. Genomic DNA of the proband's mother and 75 controls
      (50 males and 25 females) living in the same area as the proband was also
      examined. RESULTS: Sequencing of the cDNA revealed a substitution of G to A in
      codon 156 of alpha-Gal A, resulting in a single amino acid change from alanine to
      threonine (A156T). The mutation can be detected with PCR-RFLP with SfaNI
      digestion. This technique revealed that the mother was a heterozygote of A156T
      with no A156T noted in the 100 haplotypes of the controls. With a vigorous search
      of the same mutation in the literature, no previous description was found other
      than one case listed in several review papers as a classic phenotype without any
      other information. In our study, we examined A156T in a pedigree and demonstrated
      that the mutation was not a polymorphic variant in our area. CONCLUSION: Taken
      together, the present results strongly suggest that the missense mutation, A156T,
      in the alpha-Gal A gene causes typical Fabry disease.

PMID- 11316247
TI  - Central and extrapontine myelinolysis in a patient in spite of a careful
      correction of hyponatremia.
AB  - We report the case of a 54-year-old alcoholic female patient who was hospitalized
      for neurologic alterations along with a severe hyponatremia (plasma Na+: 97
      mEq/l). She suffered from potomania and was given, a few days before admission, a
      thiazide diuretic for hypertension. A careful correction of plasma Na+ levels was
      initiated over a 48-hour period (rate of correction < 10 mEq/l/24h) in order to
      avoid brain demyelination. After a 2-day period of clinical improvement, her
      neurologic condition started to deteriorate. By the 5th day of admission, she
      became tetraplegic, presented pseudobulbar palsy, ataxia, strabism,
      extrapyramidal stiffness and clouding of consciousness. Scintigraphic and MRI
      investigations demonstrated pontine and extrapontine lesions associated with
      Gayet-Wernicke encephalopathy. After correction of ionic disorders (hyponatremia,
      hypokaliemia) and vitamin B (thiamine) deficiency, the patient almost completely
      recovered without notable disabilities. This case illustrates that profound
      hyponatremia, in a paradigm of slow onset, can be compatible with life. It also
      demonstrates that demyelinating lesions, usually considered as a consequence of a
      too fast correction of hyponatremia, may occur despite the strict observance of
      recent guidelines. There is increasing evidence to suggest that pontine swelling
      and dysfunction may sometimes occur in alcoholic patients even in absence of
      disturbance in plasma Na+ levels. It is therefore of importance, while managing a
      hyponatremic alcoholic patient, to identify additional risk factors
      (hypokaliemia, hypophosphoremia, seizure-induced hypoxemia, malnutrition with
      vitamin B deficiency) for brain demyelination and to correct them appropriately.

PMID- 11316248
TI  - Acute renal failure from hemoglobinuric and interstitial nephritis secondary to
      iodine and mefenamic acid.
AB  - Mefenamic acid ingestion, usually in excess and over prolonged period is known to
      produce interstitial nephritis, or less commonly papillary necrosis, with acute
      renal failure. However, it is not dose-dependent for the induction of
      tubulointerstitial damage. Excess iodine ingestion is known to produce toxicity
      and possible death, but acute renal failure is rare. There is evidence from
      clinical and experimental data that iodine has toxic effect on tubular epithelial
      cells. Iodine has not been documented to produce red cell hemolysis and
      hemoglobinuria. We present a unique case of acute renal failure from
      hemoglobinuric and acute interstitial nephritis secondary to suicidal ingestion
      of potassium iodide solution and also ingestion of a few mefenamic acid tablets.
      These agents led to potentiation of the renal injury from hemoglobinuric
      tubulopathy, probably from the iodine, and renal dysfunction from alteration of
      renal perfusion by selective COX-1 inhibition of prostaglandin production, and
      induction of acute interstitial nephritis from mefenamic acid, leading to acute
      renal failure which was reversible by hemodialysis and supportive therapy.

PMID- 11316249
TI  - Chloramine-induced hemolysis associated with neurological symptoms in a home
      hemodialysis patient.

PMID- 11316250
TI  - Anti-proteinuric effect of angiotension II receptor antagonist losartan in cases
      with glomerular lesions.

PMID- 11316251
TI  - Elevated tissue factor levels in children with hemolytic uremic syndrome.

PMID- 11316252
TI  - Serum remnant lipoprotein levels in nephrotic syndrome.

PMID- 11316253
TI  - Erythropoietin-resistant refractory renal anemia: effects of oral L-carnitine
      supplementation.

PMID- 11316254
TI  - RPA position on the role of non-physician medical personnel in delivering
      nephrologic care. Part 1 of 3.

PMID- 11316255
TI  - Altered inhibition of the rat skeletal ryanodine receptor/calcium release channel
      by magnesium in the presence of ATP.
AB  - Magnesium-induced inhibition of the skeletal ryanodine receptor/calcium-release
      channel (RyR) was studied in the presence and absence of ATP under isolated
      conditions and in situ, by examining the RyR incorporated into a planar lipid
      bilayer and the calcium release flux (Rrel) in isolated single fibres mounted in
      the double Vaseline gap system. When the incorporated RyR had been activated by
      calcium (50 microM) in the absence of ATP, the magnesium-induced inhibition
      showed co-operativity with a Hill coefficient (N) of 1.83 and a half-inhibitory
      concentration (IC50) of 635 microM. When the open probability was measured in the
      presence of 5 mM ATP and at a low calcium concentration, the magnesium-induced
      inhibition was non-cooperative (N=1.1, IC50= 860 microM). In isolated muscle
      fibres, in the presence of ATP, lowering the intracellular magnesium
      concentration ([Mg2+]i) increased the maximal Rrel and shifted its voltage
      dependence to more negative membrane potentials. Increasing [Mg2+]i had the
      opposite effect. The concentration dependence was described with an IC50 of 174
      microM, N=1, under depolarized conditions and showed a tenfold increase in
      affinity in polarized fibres. At the concentration required for the measurements
      from isolated fibres, ATP had a full activatory effect on the isolated channel.
      At a low calcium concentration, the RyR had two ATP-binding sites with half
      activatory concentrations of 19 and 350 microM, respectively.

PMID- 11316256
TI  - Forskolin modulation of desensitization at GABA(A) and glycine receptors is not
      mediated by cAMP-dependent protein kinase in isolated carp amacrine-like cells.
AB  - The effects of forskolin on gamma-aminobutyric acid type-A (GABA(A)) and glycine
      receptors in amacrine-like cells of carp (Carassius auratus) retina were studied
      using patch-clamp techniques. Application of 50 microM forskolin markedly
      accelerated the desensitization of whole-cell responses induced by 100 microM
      GABA or glycine without changing the peak amplitude of the response. Both 8
      bromoadenosine 3',5'-cyclic monophosphate (8-Br-cAMP) and 3-isobutyl-1 
      methylxanthine (IBMX) (500 microM) failed to accelerate the desensitization of
      these two receptors. Protein kinase A (PKA) inhibitors, N- [2-[(p
      bromocinnamyl)amino]ethyl)-5-isoquinolinesulfonamide dihydrochloride (H-89) and N
      [2-(methylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride (H-8), could not
      block these effects of forskolin. An inactive analogue of forskolin, 1,9
      dideoxyforskolin (DFSK), accelerated the desensitization effectively. These
      results suggest that forskolin's effects are not mediated by activation of the
      PKA pathway. Moreover, similar results were obtained using excised outside-out
      patches of these cells, suggesting that forskolin may act on an extracellular
      site(s). The neurosteroids 5alpha-pregnane-3alpha,21 -diol-20-one (THDOC) and 5
      pregnen-31 -ol-20-one sulfate sodium (PS), structural analogues of forskolin,
      accelerated the desensitization of these receptors without changing the peak
      amplitudes, thus mimicking forskolin's effects. Furthermore, PS interacted with
      forskolin on these receptors so as to slow down the responses. These results
      raise the possibility that forskolin acts directly on an extracellular site(s) of
      the GABA(A) and glycine receptors, shared with neurosteroids, in carp amacrine
      like cells.

PMID- 11316257
TI  - Voltage-gated sodium channel (SkM1) content in dystrophin-deficient muscle.
AB  - The membrane cytoskeleton is increasingly considered as both an anchor and a
      functional modulator for ion channels. The cytoskeletal disruptions that occur in
      the absence of dystrophin led us to investigate the voltage-gated sodium channel
      (SkM1) content in the extensor digitorum longus (EDL) muscle of the dystrophin
      deficient mdx mouse. Levels of SkM1 mRNA were determined by semiquantitative
      reverse transcriptase polymerase chain reaction (RT-PCR). A C-terminal portion of
      the mouse-specific SkM1 alpha-subunit cDNA (mScn4a) was identified first. SkM1
      mRNA levels were as abundant in mdx as in normal muscle, thus suggesting that the
      transcriptional rate of SkM1 remains unchanged in mdx muscle. However, SkMI
      density in the extrajunctional sarcolemma was shown to be significantly reduced
      in mdx muscle, using confocal immunofluorescence image analysis. This decrease
      was found to be associated with a reduction in the number of SkM1-rich fast
      twitch IIb fibres in mdx muscle. In addition, lowered SkM1 sarcolemmal labelling
      was found in all mdx fibres regardless of their metabolic type. These results
      suggest the existence of a perturbation of SkM1 anchorage to the plasma membrane.
      Such an alteration is likely to be related to the 50% decrease in mdx muscle of
      the dystrophin-associated syntrophins, which are presumed to be involved in SkM1
      anchorage. However, the moderate reduction in SkM1 density (-12.7%) observed in
      mdx muscle argues in favour of a non-exclusive role of syntrophins in SkM1
      anchorage and suggests that other membrane-associated proteins are probably also
      involved.

PMID- 11316258
TI  - Co-operativity between mouse connexin30 gap junction channels.
AB  - HeLa cells stably transfected with mouse cDNA coding for connexin30 (Cx30) were
      used to study the electrical properties of gap junction channels. The experiments
      involved the measurement of intercellular currents (Ij) from cell pairs using
      dual whole-cell recording with the patch-clamp method. The aim was to compare Ij
      from cell pairs whose gap junctions consisted of a single channel and cell pairs
      whose gap junctions consisted of many channels. We found that both the ensemble
      average currents gained from single-channel records and the currents obtained
      from multichannel records inactivated exponentially with time. However, the
      former inactivated significantly slower than the latter. At ajunctional voltage
      (Vj) of 50 mV, the time constants of inactivation (tau(i)) were 8.1 s and 1.6 s,
      respectively. Moreover, the ratio tau(i)(single-channel)/tau(i)(multichannel)
      turned out to be voltage sensitive, i.e. it decreased with increasing V(j) These
      observations suggest that the operation of Cx30 gap junction channels in the
      multichannel configuration involves co-operative interactions.

PMID- 11316259
TI  - Secretin stimulates HCO3(-) and acetate efflux but not Na+/HCO3(-) uptake in rat
      pancreatic ducts.
AB  - Pancreatic ducts secrete HCO3(-), but transport mechanisms are unresolved and
      possibly vary between species. Our aim was to study the intracellular pH (pHi)
      regulation and thus H+/HCO3- transport in rat pancreatic ducts. Of particular
      interest was the Na+/HCO3(-) cotransporter, thought to be important in HCO3(-) 
      transporting epithelia. pHi was measured with BCECF in freshly isolated
      intralobular ducts. A reduction in extracellular Na+ concentration or application
      of HOE 694 (1 microM) decreased pHi by 0.1 to 0.6 pH units, demonstrating Na+/H+
      exchanger activity. A reduction in extracellular Cl- concentration or addition of
      H2DIDS (10 microM) increased pHi by 0.1 to 0.5 pH units, demonstrating Cl-/
      HCO(3)- (OH ) exchanger activity. In experimental acidosis, extracellular HCO3(
      )/CO2 buffer did not increase the rate of pHi recovery, indicating that provision
      of HCO3(-) by the Na+/HCO3(-) cotransporter was not apparent. Most importantly,
      Na+/HCO3(-) cotransport was not stimulated by secretin (1 nM). In contrast, in
      experimental alkalosis the pHi recovery was increased in HCO3(-)/CO2 buffer,
      possibly due to Na+/HCO3(-) cotransport in the efflux mode. Secretin (1 nM) and
      carbachol (1 microM) stimulated HCO3(-) efflux, which can account for the
      observed HCO3(-) concentrations in rat pancreatic juice. Acetate and HCO3(-)
      buffers were handled similarly, indicating similar transport mechanisms in
      pancreatic ducts.

PMID- 11316260
TI  - Cyclic-nucleotide-gated channels: pore topology in desensitizing E19A mutants.
AB  - In cyclic-nucleotide-gated "CNG" channels, the pore-loop "P-loop" is formed by
      the amino acid residues R345-S371 (here called R1-S27). Residue E19 determines
      the channel's interaction with extracellular divalent cations and contributes to
      ion conduction. Neutralization of this residue with alanine introduces channel
      desensitization. We have used serial cysteine mutagenesis to study P-loop
      topology in the alpha subunit of the mammalian rod CNG channels containing the
      E19A substitution. The pore topology was tested in the closed channel state and,
      when cGMP was present, during and after desensitization. With E19A substitution,
      the T15C, T16C, I17C and T20C mutants desensitized more slowly than controls.
      Moreover, the typical rundown produced by the I17C substitution in the wild-type
      "w.t." background was considerably reduced. Overall, with the E19A substitution,
      the accessibility pattern tested by applying the thiol-specific reagents Cd2+ and
      MTSET from the cytoplasmic side of the plasma membrane was similar to that
      observed with the w.t. Moreover, P22C channels were not inhibited by Cd2+ and
      MTSET (which do not cross the lipid bilayer) applied from the inside, but were
      blocked by MTSEA (which permeates the plasma membrane) also applied from the
      inside. This suggests that the residues following E19 remain accessible from the
      external side after E19A substitution. Thus, although the residues T15 to T20
      seemed to participate in the structural rearrangements producing desensitization,
      no major P-loop remodelling occurs in desensitizing channels.

PMID- 11316261
TI  - Rapid activation of Na+/H+-exchange in MDCK cells by aldosterone involves MAP
      kinase ERK1/2.
AB  - The mineralocorticoid aldosterone is essential for the adequate regulation of
      electrolyte homeostasis, extracellular volume and blood pressure. As a steroid
      hormone it influences cellular functions by genomic actions. Previously it has
      been shown that aldosterone can activate Na+/H+-exchange (NHE) by a rapid,
      nongenomic mechanism. Because (1) NHE can be regulated by ERK1/2 (extracellular
      signal-regulated kinase) and (2) steroids have been reported to rapidly activate
      ERK1/2, we tested the hypothesis that activation of NHE by aldosterone involves
      ERK1/2, using MDCK-C11 cells. We show that nanomolar concentrations of
      aldosterone induce a rapid, non-genomic activation of NHE, which is characterized
      by an increased affinity for H+ with minor changes in the maximum transport rate.
      Accordingly, aldosterone led to an increase of cytosolic steady-state pH. The
      aldosterone-induced activation of NHE was prevented by the two specific
      inhibitors of ERK1/2 activation, PD 98059 (2.5 x 10(-5) mol/l) and U0126 (10(-5)
      mol/l). Furthermore, in the presence of U0126 there was no aldosterone-induced
      increase of steady-state pH. Finally, aldosterone induced a rapid phosphorylation
      of ERK1/2, indicating its ability to activate ERK1/2. The data presented here
      support the hypothesis that the rapid activation of NHE by aldosterone at
      nanomolar concentrations involves ERK1/2. Thus, in certain cell types, the MAPK
      cascade may represent an additional pathway mediating rapid aldosterone effects.

PMID- 11316262
TI  - Swelling-activated taurine and K+ transport in human cervical cancer cells:
      association with cell cycle progression.
AB  - The aim of this study was to investigate swelling-activated taurine and K+
      transport in human cervical cancer cells under various culture conditions,
      testing the hypothesis that the progression of cell cycle was accompanied by
      differential activities of swelling-activated transport pathways. Aphidicolin, an
      inhibitor of deoxyribonucleic acid (DNA) synthesis, was used to synchronize the
      cell cycle. The distribution of cell cycle stage was determined by fluorescence
      activated cell sorting (FACS). Hypotonicity activated taurine efflux, which was
      sensitive to tamoxifen and 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB).
      Cell swelling also induced both Cl- -dependent and -independent K+ (86Rb+)
      efflux, presumably mediated by KCl cotransport (KCC) and Ca2+ -activated K+
      channels, respectively. Cell cycle arrest in G0/G1 was accompanied by a
      remarkable decrease in the rate constant for swelling-activated taurine efflux,
      from 0.20+/-0.007 to 0.026+/-0.002 min(-1) (n=6). The activity of swelling
      activated taurine efflux recovered progressively on re-entry into the cell cycle.
      After removal of aphidicolin and culture with 10% fetal calf serum for 10 h, the
      rate constant increased significantly from 0.026+/-0.002 to 0.093+/-0.002 min(-1)
      (n=6). After 24 h release from aphidicolin, the efflux rate constant had
      increased further to 0.195+/-0.006 min(-1) (n=6), a value not significantly
      different from that in normally proliferating cells. The differential activities
      of swelling-activated taurine transport matched well with our previous study
      showing a volume-sensitive anion channel associated with cell cycle progression.
      In contrast to the differential activities of swelling-activated taurine
      transport, swelling-activated K+ (86Rb+) transport was independent of the
      progression of cell cycle. Most importantly, pharmacological blockade of swelling
      activated taurine efflux by tamoxifen or NPPB caused proliferating cervical
      cancer cells to arrest in G0/G1, suggesting that the activity of this efflux was
      associated with G1/S checkpoint progression. This study provides new and
      important information on the functional significance of swelling-activated
      transport system in the regulation of cell cycle clock of human cervical cancer
      cells.

PMID- 11316263
TI  - Regulation of InsP3-mediated Ca2+ release by CaMKII in Xenopus oocytes.
AB  - Inhibition of calmodulin (CaM) sensitizes Ca2+ release mediated by D-myo-inositol
      (1,4,5)-trisphosphate (InsP3) in Xenoplus oocytes, which results in spontaneous
      Ca2+ -dependent Cl- current oscillations or in a shift of the concentration
      threshold for lysophosphatidic acid (LPA) by a tenfold factor. The oscillatory
      currents appear at a low initial Ca2+ concentration and without any significant
      increase in the inositol phosphate (InsPs) concentrations. These data led us to
      rule out the direct involvement of CaM, as well as the implied involvement of
      InsP3 3-kinase. The response to intracellular injection of the non-metabolizable
      InsP3 analog 3-deoxy-3-fluoro InsP3 (InsP3-F) is obviously affected by previous
      treatment with CaM inhibitory peptide. Furthermore, these effects have been
      consistently obtained with specific CaMKII inhibitors such as KN-93 and AIP. CaM
      plays a key role in the Ca2+-dependent inactivation of type I InsP3 receptors.
      The experiments presented hereby allow us to postulate that CaM could also exert
      its inhibitory effect through CaMKII in a way that does not involve InsP3
      metabolism regulation. It is concluded that CaMKII could participate in Ca2+
      evoked inhibition of InsP3-mediated Ca2+ release by inhibiting the InsP3
      receptor.

PMID- 11316264
TI  - Effect of NaPi-mediated phosphate transport on intracellular pH.
AB  - Extracellular pH has been shown previously to influence transport via type-II
      Na+/phosphate (NaPi) transporters by modifying the affinity of the carrier for
      Na+ and by altering the availability of divalent and monovalent phosphate. As the
      transport of monovalent phosphate would be expected to acidify, and that of
      divalent phosphate to alkalinize the cell interior, the effect of phosphate
      transport on cytosolic pH was studied using ion selective microelectrodes in
      Xenopus oocytes expressing NaPi-3 or NaPi-5. At an alkaline extracellular pH
      (pHe) of 8.0, addition of phosphate elicited a strong inward current,
      depolarization of the cell membrane and cytosolic alkalinization. At pHe 6.0 the
      phosphate-induced inward current and depolarization were reduced and the
      alkalinization completely abolished. In conclusion, at alkaline pHe phosphate
      transport is enhanced and the transport of divalent phosphate prevails. At pHe
      6.0, phosphate transport is attenuated and is accomplished by transport of both
      divalent and monovalent phosphate.

PMID- 11316265
TI  - Differences in the protein-kinase-A-dependent regulation of CFTR Cl- channels and
      Na+-K+ pumps in guinea-pig ventricular myocytes.
AB  - Protein-kinase-A- (PKA-) dependent regulation of cystic fibrosis transmembrane
      conductance regulator (CFTR) Cl- current (I(CFTR)) and Na+-K+ pump current (Ip)
      was studied in single guinea-pig ventricular myocytes. Both currents were
      measured simultaneously by means of whole-cell recording at 30 degrees C. The
      adenylyl cyclase activator forskolin was used to stimulate PKA activity. At -20
      mV, forskolin (4 microM) induced a fast activation of I(CFTR) and a delayed
      stimulation of Ip. Despite the strikingly different time courses, however, the
      potency of the drug to regulate both currents was identical. Half-maximal
      activation of I(CFTR) and stimulation of Ip, respectively, were observed at 9.6 x
      10(-8) M and 9.9 x 10(-8) M forskolin. Inclusion of a specific peptide inhibitor
      of PKA in the pipette solution (PKI, 20 microM) blocked forskolin's effect on Ip.
      However, regardless of the time allowed for cell dialysis, there still was a
      marked, transient activation of I(CFTR), which could be prevented by: (1) a short
      pre-activation of I(CFTR) with forskolin or (2) the additional inclusion in the
      pipette solution of a synthetic peptide (Ht31 peptide, 60 microM) that interferes
      with PKA binding to its anchoring proteins. Thus, there is a tight functional
      coupling between PKA and CFTR Cl- channels in guinea-pig ventricular myocytes.
      The coupling is probably due to the close physical proximity of channels and
      kinases mediated by PKA anchoring proteins. Na+-K+ pumps, on the other hand,
      though also regulated by PKA, appear to be loosely coupled to the kinases.

PMID- 11316266
TI  - Tetrabutylammonium: a selective blocker of the somatostatin-activated
      hyperpolarizing current in mouse AtT-20 corticotrophs.
AB  - To obtain a clearer understanding of the mechanisms by which somatostatin
      modulates stimulus-secretion coupling in neuroendocrine cells, we investigated
      the pharmacology of the somatostatin-activated inward rectifier in mouse
      pituitary tumour cells (AtT-20 corticotrophs). Individual AtT-20 cells displayed
      spontaneous, long-lasting action potentials that caused transient spikes in
      cytosolic [Ca2+] ([Ca]i). Application of 1-10 nM somatostatin led to membrane
      hyperpolarization and loss of [Ca]i spiking activity. Voltage-clamp recordings
      revealed that the somatostatin-induced hyperpolarization was due to an inwardly
      rectifying K+ current. Tetrabutyl-ammonium (TBA+) inhibited both outward and
      inward currents through the inward rectifier, whereas Cs+ blocked only inward
      current and tetraethylammonium (TEA+) was completely ineffective in blocking
      somatostatin-activated currents. However TEA+, but neither TBA+ nor Cs+, blocked
      voltage-gated outward currents. Correspondingly, TBA+ abolished the
      hyperpolarizing effects of somatostatin and, of the three K+ channel blockers,
      only TBA+ prevented the somatostatin-induced inhibition of [Ca]i spiking. TBA+
      may thus prove a useful tool in elucidating the underlying mechanisms by which
      somatostatin affects the secretory activity of neuroendocrine cells.

PMID- 11316267
TI  - Coupling of L-type calcium channels to neurotransmitter release at mouse motor
      nerve terminals.
AB  - Previously, we have presented evidence for the presence of L-type voltage
      dependent Ca2+ channels (VDCC) in 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'
      tetraacetic acid, (acetoxymethyl)ester (BAPTA-AM)-incubated motor nerve terminals
      (MNTs) of the levator auris muscle of mature mice. The aim of the present work
      was to study the coupling of these L-type VDCC to neurotransmitter release by
      inhibiting protein phosphatases. We thus studied the effects of the protein
      phosphatase inhibitors okadaic acid (OA) and pervanadate on quantal content (QC)
      of transmitter release with the P/Q-type channels fully blocked. The QC was not
      significantly different under the three experimental conditions tested:
      incubation with dimethylsulphoxide (DMSO), ethylene-glycol-bis(beta
      aminoethylether)-N,N,N',N'-tetraacetic acid, (acetoxymethyl)ester (EGTA-AM) and
      BAPTA-AM. After preincubation with OA (1 microM), but not with pervanadate, QC
      increased substantially in the BAPTA-AM-incubated (up to 400%) MNT, but not in
      those incubated with DMSO or EGTA-AM. The OA-induced increment of QC was
      attenuated greatly (approximately 95% reduction) by preincubation with either
      nitrendipine (10 microM) or calciseptine (300 nM). The effect of OA (1 microM)
      and pervanadate (0.1 mM) on spontaneous neurotransmitter release was also
      studied. After preincubation with OA, but not per-vanadate, miniature end-plate
      potential (MEPP) frequency increased only in the BAPTA-AM-incubated MNT (up to
      700% increment). This response was attenuated (by approximately 80%) by
      nitrendipine (10 microM) or calciseptine (300 nM). In contrast, neither omega
      agatoxin IVA (120 nM) nor omega-conotoxin GVIA (1 microM) affected this OA
      induced increment significantly. We also evaluated the relationship between QC
      and extracellular [Ca2+] ([Ca2+]o) in BAPTA-AM-incubated MNT. Under conditions in
      which only P/Q-type VDCC were available to participate in neurotransmitter
      release, QC increased as [Ca2+]o was raised from 0.5 to 2 mM. However, when only
      L-type VDCC were available, QC increased when [Ca2+]o increased from 0.5 to 1 mM,
      but decreased significantly at 2 mM. The mean latency for P/Q-type VDCC-mediated
      EPP was 1.7-1.9 ms; for L-type VDCC-mediated EPP, 1.9-2.5 ms. The rise time of
      the L-type VDCC mediated EPP was significantly slower than that mediated by P/Q
      type VDCC. Preincubation with H-7 (100 microM), a potent inhibitor of protein
      kinase C (PKC) and adenosine 3',5'cyclic monophosphate (cAMP)-dependent protein
      kinase (PKA), attenuated the OA-induced increment of both QC and MEPP frequency
      (50% and 70% decrement, respectively), suggesting the participation of at least
      these two protein kinases in the coupling of L-type VDCC. In summary, our results
      show coupling of L-type VDCC to neurotransmitter release when protein
      phosphatases are inhibited and intracellular [Ca2+] is buffered by the fast
      chelator BAPTA.

PMID- 11316268
TI  - Subtypes of low voltage-activated Ca2+ channels in laterodorsal thalamic neurons:
      possible localization and physiological roles.
AB  - The macroscopic, low-voltage-activated (LVA or T-type) Ca2+ current in isolated
      associative (or local-circuit) neurons from the laterodorsal thalamic nucleus of
      14-17-day old rats was dissected into two components ("fast" and "slow"),
      corresponding to the activation of two LVA channel subtypes, based on the
      difference in the kinetics of inactivation and recovery from inactivation. The
      steady-state activation and inactivation properties of the channel subtypes
      endowed slow channels with a substantial window current, whereas fast channels
      had almost no such current. Fast channels were almost 2 times more sensitive to
      30 microM nifedipine (78% inhibition), 10 microM flunarizine (92% inhibition) and
      1 microM La3+ (87% inhibition), but about 1.8-fold less sensitive to 100 microM
      Ni2+ (32% inhibition) than slow channels (40%, 52%, 46% and 56% inhibition
      respectively). Both channels were almost equally sensitive to 100 microM
      amiloride (58% and 51% inhibition of fast and slow channels respectively).
      Comparison of the fast and slow LVA Ca2+ current amplitudes and densities between
      enzymatically isolated and intact (in brain slices) neurons suggest a predominant
      localization of the fast channels in soma and the proximal dendrites that remain
      intact during isolation procedure, whereas the slow channels are more evenly
      distributed with some preference to the distal areas. These data, together with
      our previous studies, support the notion of two LVA Ca2+ channel subtypes in
      associative thalamic neurons and suggest a role for the slow channels in
      providing the constant Ca2+ influx necessary for the outgrowth of the neurites
      and for the fast channels in the generation of low-threshold Ca2+ spikes and
      bursting activity.

PMID- 11316269
TI  - Very mild exposure to hypoxia for 8 h can induce ventilatory acclimatization in
      humans.
AB  - Ventilatory acclimatization to altitude is associated with a progressive increase
      in ventilation, a progressive decrease in end-tidal PCO2 and a progressive
      increase in the acute ventilatory sensitivity to hypoxia. Ventilatory
      acclimatization has been observed with mild exposure to hypoxia when the duration
      of exposure has been of some length (e.g. days), and with shorter duration
      exposures (e.g. 8 h) when the degree of hypoxia has been more severe. The purpose
      of this study was to determine whether short-duration exposures to very mild
      hypoxia, such as are commonly associated with the reduction in cabin pressure
      during commercial airline flight, can also induce some degree of ventilatory
      acclimatization. Twelve subjects were exposed in a chamber to both 8 h mild
      hypoxia (inspired PO2 127 mmHg) and 8 h air-breathing as a control. Exposures
      were on different days in random order. Following the hypoxic exposure, there was
      a significant reduction in end-tidal PCO2 during air breathing (from 39.2+/-1.8
      to 38.11+/-1.5 mmHg, mean +/- SD, P<0.05), and a significant increase in
      ventilatory sensitivity to hypoxia (from 0.84+/-0.54 l/min/% to 1.13+/-0.66
      l/min/%, P<0.05). We conclude that shortterm exposures to very mild hypoxia do
      induce significant acclimatization within the respiratory control system.

PMID- 11316270
TI  - Inhibition of endothelin-1 by the competitive ET(A) receptor antagonist Ro 61
      1790 reduces lesion volume after cold injury in the rat.
AB  - The aim of the present study was to investigate whether endothelin-1 (ET-1) in
      cerebral arteries is inhibited by the new, non-peptidergic ET(A) receptor
      antagonist Ro 61-1790 and, if it is, whether that inhibition reduces the lesion
      volume induced by cold injury in the parietal cortex. In vitro experiments were
      performed by measuring the isometric contractions of the rat middle cerebral and
      basilar arteries. A cold lesion was induced in vivo by the application of a pre
      cooled (-78 degrees C) copper cylinder (diameter 3 mm) to the intact dura of rats
      for 6 s. After 24 h, lesion volume was determined by the triphenyltetrazolium
      method. In vitro, ET-1 (10(-12) - 3x10(-7) M) caused a dose-dependent contraction
      under resting conditions in the middle cerebral and basilar arteries of control
      rats. Ro 61-1790 (3x10(-9) M, 10(-7) M) shifted the concentration-effect curves
      for ET-1 in a parallel fashion (Emax unaltered). Post-treatment with Ro 61-1790
      (10(-7)-10(-5) M) also inhibited the prior contraction elicited by ET-1 (3x10(-9)
      M) significantly. In vitro ET-1 application 3 h after the intracerebroventricular
      in vivo administration of Ro 61-1790 showed that the antagonist had reached the
      arteries and was bound to their ET(A) receptors. Intracerebroventricular pre
      treatment of Ro 61-1790 reduced significantly the lesion volume by 23% after the
      injury. We conclude that ET-1 is involved in the development of secondary brain
      damage and that intracerebroventricular treatment with Ro 61-1790 reduces the
      size of the brain lesion caused by cold injury.

PMID- 11316271
TI  - Functional integrity of the vesicle transporting machinery is required for
      complete activation of cFTR expressed in xenopus laevis oocytes.
AB  - We expressed the human cystic fibrosis transmembrane conductance regulator (CFTR)
      in oocytes of the South African clawed frog Xenopus laevis. We performed
      simultaneous and continuous recording of membrane current (Im), conductance (Gm)
      and capacitance (Cm), the latter being a direct measure of membrane surface area.
      A cAMP-cocktail containing cAMP and isobutylmethylxanthine (IBMX) increased all
      parameters, demonstrating that CFTR activation was partly achieved by exocytotic
      delivery and insertion of preformed CFTR molecules into the plasma membrane. CFTR
      currents after cAMP-cocktail were correlated with the capacitance of the oocytes:
      oocytes with larger Cm exhibited larger currents. Expression of CFTR itself did
      not change the Cm of the oocytes. However, activation of CFTR with cAMP-cocktail
      increased Im and Gm 15- and 20-fold, respectively while membrane surface area
      increased by about 7%, indicating the functional insertion of preformed CFTR into
      the plasma membrane. While cAMP-cocktail yielded maximal CFTR stimulation, IBMX
      alone, but not caffeine or theophylline, was sufficient to stimulate more than
      half of the increases in Im and Gm as observed with cAMP-cocktail. Since Cm was
      not significantly stimulated by IBMX, we conclude that IBMX alone activated the
      CFTR channels already present in the oocyte membrane. CFTR stimulation by cAMP
      cocktail was independent of external Ca2+ and ATP had no additional activating
      potency. The role of protein trafficking in the activation of CFTR evoked by
      increases of cytoplasmic cAMP was assessed by measuring the effects of brefeldin
      A (BFA), nocodazole and primaquine on the bioelectric parameters and membrane
      surface area. All these compounds that interfere with the protein trafficking
      machinery at different stages prevented the translocation of CFTR from
      intracellular pools to the plasma membrane. These data confirm and extend our
      previous observations that CFTR expressed in Xenopus laevis oocytes is activated
      via dual pathways including direct activation of CFTR already present in the
      membrane and exocytotic insertion of preformed CFTR channels into the membrane.
      Furthermore, we show that complete activation of CFTR requires an intact protein
      trafficking machinery.

PMID- 11316272
TI  - The ICN code of ethics for nurses: shared values in a troubled world.

PMID- 11316273
TI  - The right-to-die and the duty-to-die: perceptions of nurses in the West and in
      Japan.
AB  - The right-to-die means that the terminally ill person has the right to refuse
      further treatment. The duty-to-die means that terminally ill persons feel that
      they have no choice and must refuse treatment because of social factors such as
      family burden or financial cost to society. This article describes the
      perceptions of a sample of 72 Japanese nurses and 71 counterparts from the West.
      The right-to-die received support from all of the western and from a majority of
      the Japanese sample. However, the duty-to-die received weaker support from the
      West and rather strong disagreement from Japan. Themes emerged in the two groups
      from a content analysis of their reactions to the major concepts of right-to-die
      and duty-to-die, and these included autonomy, values surrounding life, justice,
      family as a possible coercive agent and family as a partner in decision making.
      Differences and similarities across the cultures in the meaning of these themes
      were explored.

PMID- 11316274
TI  - A review of the literature from developed and developing countries relating to
      the effects of hospitalization on children and parents.
AB  - There is a literature base about the care of children in hospital in developed
      nations, but little from, or about, developing countries. The aim of this review
      was to critically examine publications relating to the effect of hospitalization
      on children and their parents. 'Parents', in this context, were considered as the
      child's natural or adoptive parents, step-parents or any other context of parent
      child relationship, in other words, the primary care-giver to the child. Most of
      the work reviewed from developed countries was sourced from the nursing
      literature, while in developing countries, the available literature was largely
      from medicine. Conclusions from developed countries indicated that parents should
      be allowed to stay in hospital with their child, and that care must be
      developmental-stage appropriate. Furthermore, staff need to be educated about
      special needs of children, children should be prepared for hospital admission (if
      possible) and parents' needs met. In developing countries, the meagre literature
      available suggested that recognition of the important role parents play in a
      child's hospitalization is starting to become recognized.

PMID- 11316275
TI  - The renaissance of clinical leadership.
AB  - The purpose of this work was to explore clinical nursing leadership. The research
      was based on a critical examination of the leadership themes derived from the
      nursing literature of the United Kingdom, the United States of America and
      Australia, between 1992 and 1997. The work was also influenced by the findings
      from semistructured interviews undertaken with five clinical leaders in nursing
      from the United Kingdom, and study tours to both the United States of America and
      Australia. The findings support a proposed leadership model as a basis for
      further exploration and as a framework for contemplating clinical leadership and
      leadership preparation. A model is presented that identifies factors which
      influence leadership styles, such as external environment, internal environment,
      experience and understanding. Four leadership styles are outlined: transactional,
      transformational, connective and renaissance. These leadership styles are linked
      to nursing care approaches. A second model provides a basis for considering power
      and its impact in the workplace. Based on these findings, the contents of a
      leadership preparation course are outlined.

PMID- 11316276
TI  - New nurse graduates' understanding of competence.
AB  - This article describes the findings of a phenomenographic research approach used
      to understand the experiences of competence of new nurse graduates. The aim of
      phenomenography is to describe the qualitatively different ways in which people
      understand a phenomenon. Six new graduates, who had been employed in two
      paediatric metropolitan hospitals in Australia, participated in the research. The
      graduates were interviewed and asked to describe and draw their understanding of
      competence. The interviews were audio-taped and transcribed verbatim. Interview
      transcripts were analysed according to accepted phenomenographic methods of
      analysis. The graduates described eight conceptions of competence: competence as
      safe practice; competence as limited independence; competence as utilization of
      resources; competence as management of time and workload; competence as ethical
      practice; competence as performance of clinical skills; competence as knowledge;
      and competence as evolving. The final outcome of identification of conceptions
      led to the development of an outcome space (a diagrammatic representation of the
      logical relations between conceptions). The outcome space depicted a three-level
      hierarchical relationship between the eight conceptions of competence experienced
      within a global framework of safety. The findings contribute to nursing knowledge
      by describing the meaning of competence from the perspective of the new nurse
      graduate. The need for support and assistance by employers of new graduates is
      confirmed from the findings. New nurse graduate experiences of competence provide
      suggestions for improving undergraduate education programmes as well as
      clarification of entry-level competency standards.

PMID- 11316277
TI  - The role of the clinical nurse specialist.
AB  - In this article, the role of the clinical nurse specialist (CNS) at the
      University Hospital Insel in Bern, Switzerland, is described using four examples
      from daily practice. The first describes how the CNS may influence patient care
      by direct care, bedside teaching, or case reviews. Therefore, this form of co
      operation with the nursing teams is a very important factor for improving nursing
      care. The second example is about wound care. Although the CNS work as
      generalists on the wards, they also have their specialist fields, where they have
      in-depth knowledge, skills and expertise. The third example describes how a CNS
      initiated an interprofessional working group with the aim of improving palliative
      care and palliative medicine throughout the hospital. Although such knowledge
      already existed in the hospital, it was not easily accessible to all the health
      care professionals. The fourth example is about project management. A CNS acted
      as a project leader of a multiprofessional group for pain assessment and
      management in babies, children and adolescents. This example also shows how a
      problem occurring in daily practice can be worked out and resolved.

PMID- 11316278
TI  - Evaluating the Beta version of the International Classification for Nursing
      Practice for domain completeness, applicability of its axial structure and
      utility in clinical practice: a Norwegian project.
AB  - The purpose of this Norwegian project was to evaluate the International
      Classification for Nursing Practice (ICNP) Beta version for domain completeness,
      applicability of its axial structure and utility in clinical practice. A subset
      of terms addressing the areas of circulation and elimination were abstracted from
      the nursing records of a cardiac intensive care unit and a nursing home.
      Abstracted terms were mapped to terms in the ICNP. In the ICNP, the same or
      similar terms were found for 47% of the documented circulation terms and 69% of
      the documented elimination terms that addressed nursing phenomena. For nursing
      interventions, 27% of the documented circulation terms and 35% of the documented
      elimination terms mapped to the ICNP. The research team encountered difficulty in
      coding terms with the ICNP that expressed patients' perspectives, preferences,
      behaviours and experiences, and terms that represented signs-and-symptoms.
      Recommendations for further development of the ICNP include improvement in
      granularity, precision and conceptual definitions of terms; inclusion of time
      related terms for representing nursing phenomena; and an easier method for
      navigating around the ICNP.

PMID- 11316279
TI  - Toe transfer in congenital hand malformations.
AB  - Fifty-eight patients with congenital hand abnormalities underwent 65 toe-to-hand
      transfers. Symbrachydactyly (51 cases) was the most frequent indication. Forty
      seven second toe-to-hand transfers were performed in 44 patients. The mean follow
      up time was 5.2 years. Two failures occurred in cases in which only one artery
      was anastomosed; no failures were noted when more than one artery fed the
      transfer. Two patients with a single second-toe transfer presented with lateral
      instability of the transferred metatarsophalangeal joint. The mean active range
      of motion was 38 degrees, with a mean extension lag of 25 degrees. The mean two
      point discrimination was 5 mm. Forty-one patients used the transferred toe well,
      when performing activities of daily living and playing games. Toe-to-hand
      transfer, prior to the establishment of the grip pattern, facilitates integration
      of the transfer.

PMID- 11316280
TI  - Free vascularized fibular graft vs. Ilizarov method for post-traumatic tibial
      bone defect.
AB  - From 1991 to 1996, four free vascularized fibular grafts (FVFG) and four callus
      distraction (CD) techniques were performed for post-traumatic tibial defects at
      the authors' institute. They attempted to discern any differences of results
      between FVFGs and CDs for post-traumatic tibial defects. The mean defect length
      of the FVFG and CD groups were 7.3 cm and 4.6 cm, respectively (p < 0.05). They
      selected as contributing factors: external fixation time, complication rate,
      hospital charge, union rate, and functional score (Puno's criteria), in order to
      compare the treatment of FVFG with that of CD. The external fixation times of the
      FVFG and CD groups were 176 days and 261 days, respectively. One septic non-union
      after refracture of the grafted fibula occurred in the FVFG group. Two non-unions
      (50 percent) at the docking site occurred in the CD group. The mean total costs
      of the FVFG and CD groups were 7,398,536 yen (US $68,505) and 11,798,153 yen(US
      $109,242), respectively. The union rates of both groups were 75 percent and 100
      percent, respectively. The mean functional scores of both groups were 69.5 and
      88.8 points, respectively. The functional results of the FVFG group were as
      follows: one patient showed good results; one, fair; and two, poor. The
      functional results of the CD group were as follows: two patients showed excellent
      results; one, good; and one, fair. Both the costs and the functional outcomes
      between the two groups did not significantly differ. No clear differences between
      the two treatment groups could be determined. However, many more cases are needed
      to establish statistically significant differences between both methods.

PMID- 11316281
TI  - Elective free-tissue transfer in pediatric patients.
AB  - Twenty-two elective free-tissue transfers for reconstruction of various defects
      were performed in 20 pediatric patients over a 7-year period. Patient ages ranged
      from 5 to 17 years (mean: 12.5 years). There were six open wounds, six unstable
      scars, five tumor resection defects, three facial gunshot wounds, one facial
      paralysis, and one penis agenesis. Ten free flaps were transferred to the head
      and neck region, seven to the lower extremity, four to the upper extremity, and
      one to the genital area. Ten fasciocutaneous flaps, seven muscle or myocutaneous
      flaps, and five vascularized bone grafts were transferred. All flaps survived,
      except for one in an electrical burn patient. The success rate was 95 percent. No
      vessel spasm was observed. Children tolerated long operation periods better than
      adults. The recovery time after surgery was considerably shorter than in adults.
      The mean operative time was 6 hr, and the average hospital stay was 12 days. The
      mean follow-up period was 27 months. Results of this study indicate that
      microvascular free-tissue transfer is a safe and reliable method for the
      reconstruction of various defects in children.

PMID- 11316282
TI  - Oral-cavity hair growth after free-flap transfer: case report.
AB  - It sometimes happens that hair will grow well after a free-flap transfer. But
      this is a report of an experience of excessive hair growth after reconstruction
      of a middle pharyngeal defect, using a free, vascularized, radial, forearm flap.
      This is a relatively rare occurrence.

PMID- 11316283
TI  - Basic fibroblast growth factor induced angiogenesis and prefabricated flap
      survival.
AB  - Prefabrication of a latissimus dorsi myocutaneous flap was performed in adult
      male Landrace pigs. Gelfoam sponges were used as a delivery system for basic
      fibroblast growth factor (bFGF) at the muscle-subcutaneous tissue interface. Skin
      survival and angiogenesis were augmented in the growth-factor-treated animals.
      These data support the use of basic fibroblast growth factor to enhance flap
      prefabrication.

PMID- 11316284
TI  - Fetal spinal-cord allograft as a substitute for peripheral-nerve reconstruction:
      a preliminary experimental and histologic study.
AB  - The aim of this preliminary experimental study consisted of an exploration of the
      suitability of fetal spinal-cord allograft as an alternative guiding conduit for
      bridging peripheral-nerve defects, since fetal tissue is considered to be less
      immunogenic than tissue from adults or maturely born individuals. The experiment
      was carried out with 10 Long Evans inbred rats. Within the control group,
      autologous sural-nerve grafts served to bridge an artificially created defect of
      1.5 cm along the course of the sciatic nerve in the thigh of adult male rats. On
      the contralateral thigh, a defect of the same size was bridged by spinal cord,
      taken from 17- to 20-day old fetuses. Ten weeks thereafter, the reconstructed
      nerves were examined histologically. Compared to the autologous nerve grafts with
      optimal regeneration, the spinal-cord grafts showed less ingrowth of axons. But,
      surprisingly, an exceptionally long survival time of astrocytes and other nerve
      cells resulted while, at the graft margin, bundles of astrocytes apparently
      served as a conduit for ingrowing axons. Using fetal spinal-cord allograft to
      reconstruct peripheral-nerve defects may present a future alternative for
      coexisting methods, but further studies with longer follow-ups, a greater number
      of larger animals, and with the additional evaluation of immunologic
      interactions, should be attempted, to draw clear conclusions.

PMID- 11316285
TI  - Growth factor may decrease muscle atrophy secondary to denervation.
AB  - Despite modern microsurgical techniques, functional outcomes following brachial
      plexus reconstruction and peripheral-nerve repair are usually unsatisfactory,
      because irreversible muscle atrophy develops before reinnervation occurs. Insulin
      growth factor-1 (IGF-1) has been shown to improve muscle regeneration after
      injury, and may have a role in muscle preservation following denervation. This
      study evaluated the histologic, immunohistochemical, and electrophysiologic
      differences between normal and denervated muscle over an 8-week time period, and
      also evaluated the effects of injecting IGF-1 into denervated muscle. Denervated
      mice gastrocnemius muscles demonstrated a decrease in muscle diameter, a decrease
      in muscle weight, early nuclear proliferation, and a decrease in fast twitch and
      maximum tetanic strength, compared to normal gastrocnemius muscle up to 8 weeks
      following denervation. Four weeks after denervated muscle was injected with IGF-1
      at time zero, however, relative preservation of muscle diameter and weight, and
      maintenance of electrophysiologic contractile properties were observed. These
      preliminary data suggest that IGF-1 may prevent muscle atrophy secondary to
      denervation.

PMID- 11316286
TI  - Evaluation of total vs. regional blood perfusion with a laser Doppler imaging
      system in the rat epigastric flap.
AB  - Monitoring systems to measure flap survival are either invasive, touch the
      surface of the tissue, or have problems in reproducibility. The authors sought to
      determine the efficacy of a laser Doppler imaging (LDI) system to measure
      perfusion in a myocutaneous flap, by producing a two-dimensional picture of the
      flap without touching the surface. They compared total flap perfusion with
      perfusion in selected areas of interest after flap surgery. The perfusion in the
      left groin of Sprague-Dawley rats was measured before and after surface rubbing,
      skin injury, and during different lighting conditions. The perfusion of the
      epigastric flap before and over a period of 60 min after elevation was measured,
      and values were compared to pre-surgical values and to sham-operated animals.
      They determined the differences between single and running-suture techniques
      after flap surgery, as well as between venous and/or arterial occlusion. Surface
      rubbing, skin injury, and light influenced the LDI image. After flap elevation,
      total flap perfusion remained stable, while the distal area (area 8, n = 7) of
      the flap showed a statistically significant decrease in perfusion (71 +/- 5.9 vs.
      92 +/- 9.5 percent perfusion units--PU; p < .05). The proximal areas (1 to 3, n =
      7) of the flap had a higher perfusion at 60 min after flap surgery, compared with
      sham-operated (n = 8) animals (118 +/- 12.5 vs. 97 +/- 10.4 percent PU; p < .05).
      The running-suture technique was followed by decreased perfusion on the
      peripheral side of the flap, compared with the single-suture technique (73.7 +/-
      9.2 vs. 99.2 +/- 4.9 percent PU; n = 2). The LDI was able to visualize venous
      and/or arterial occlusion after flap surgery. Under standardized circumstances
      (light, temperature), the LDI was efficient in measuring regional flap
      circulation experimentally. While total flap perfusion after flap surgery
      remained stable, perfusion in the distal flap decreased significantly.

PMID- 11316287
TI  - Correlation between functional index and morphometry to evaluate recovery of the
      rat sciatic nerve following crush injury: experimental study.
AB  - An experimental study on the correlation between functional and morphologic
      recovery of crushed sciatic nerves was carried out in rats. The sciatic nerve of
      33 rats, divided into three groups, was submitted to controlled crushing injury
      on a 5-mm long segment, in a universal testing machine for 10 min with three
      different loads (100, 500, and 15,000 g, respectively). Functional recovery was
      evaluated, using a modified sciatic functional index (SFI) at weekly intervals up
      to the 60th postoperative day, at which time, the animals were sacrificed for
      histologic and morphometric studies of the nerves. Results were compared with
      those of normal untouched nerves and nerves submitted to segmentary resection
      without repair. Initial loss of function was observed in all animals with crush
      injury, but recovery to a nearly normal SFI occurred after progressively longer
      intervals (25, 39, and 53 days), as a function of load. Nerve-fiber density was
      increased in the groups submitted to lower loads, but statistically significantly
      decreased in the animals submitted to the 15,000-g crush. The authors conclude
      that the SFI is directly correlated with nerve-fiber density and, therefore, is
      an adequate tool for evaluating sciatic functional deficiency in the rat.

PMID- 11316288
TI  - Microsurgical reconstruction of the hypoplastic thumb, type IIIB.
AB  - If a classically hypoplastic thumb, type IIIA, presenting with a first
      carpometacarpal joint, is amenable to reconstruction, a type IIIB case without
      the basal joint, is classically treated by pollicization. The authors concur with
      this opinion, but found two circumstances in which reconstruction is an option in
      a type IIIB thumb, either when an adolescent asks for improvement of an unstable
      but utilized thumb, or when a parent definitely refuses pollicization. In such
      cases, a free, vascularized metatarsophalangeal joint is the first step of the
      reconstruction, followed by classic non-microsurgical steps. The authors reviewed
      five cases, with a mean follow-up of 7.8 years. Hypoplasia of the reconstructed
      thumb, and a limited pinch, allow this option only with restricted indications.

PMID- 11316289
TI  - Foot-and-mouth disease: waiting for the peak.

PMID- 11316290
TI  - Animal abuse and human violence: exploring a connection.

PMID- 11316291
TI  - Isolation of Mycoplasma bovis from bovine clinical samples in the Republic of
      Ireland.
AB  - Mycoplasma bovis was detected in 134 (18 per cent) of 736 samples of bovine lung
      tissue collected from fatal pneumonia cases in the Republic of Ireland between
      April 1995 and December 1998. The cases occurred in 95 herds and recurred in four
      of them. Other respiratory pathogens were identified in 66 per cent of the M
      bovis-positive cases, with Pasteurella species, infectious bovine rhinotracheitis
      and parainfluenza 3 virus being most frequently detected. Mastitis and arthritis
      were less common clinical signs associated with M bovis infection; 22 cases of M
      bovis mastitis and five cases of M bovis arthritis were diagnosed in five herds.

PMID- 11316292
TI  - Disease and mortality on red deer farms in New Zealand.
AB  - A longitudinal observational study of 15 red deer farms was carried out in New
      Zealand for two years from March 1992. The deer were monitored for performance
      and health problems, and farm management practices were recorded. Numbers at risk
      were 4,683 hind-years, 2,459 stag-years and 3,202 weaner-years. The numbers of
      primiparous and adult hinds at risk of losing their progeny by weaning were 653
      and 3,364, respectively. Where possible, postmortem examinations were carried
      out, and organs were sampled for histological and microbiological investigation.
      Rates of mortality varied with season with most stag and hind deaths in winter
      and weaner deaths in autumn and winter. Overall mortality rates were 1.77, 2.60
      and 5.87 per 100 deer-years for hinds, stags and weaners, respectively. Malignant
      catarrhal fever accounted for 0.53 stag and 0.17 hind deaths per 100 deer-years
      at risk Misadventure, including broken bones, accounted for 15.4 per cent of
      weaner mortalities, or 0.53 weaner mortalities per 100 weaner-three months in
      autumn. Yersiniosis was confirmed in 18.6 per cent of weaner deaths, or 1.09
      weaners per 100 weaner-years during the first six months after weaning, but was
      also suspected but unconfirmed in a further 41 per cent of weaner mortalities.
      Overall, 17 per cent of yearling hinds, and 9.2 per cent of adult hinds lost
      their progeny between pregnancy diagnosis in June and weaning in March. One
      outbreak of osteochondrosis was recorded. Mortality rates varied between farms
      and many mortalities were preventable.

PMID- 11316293
TI  - Observations on ascites in nine cattle.
AB  - Signs of ascites were observed in only nine of 1863 cattle examined over a period
      of five years. The ascites was most commonly associated with either primary or
      secondary cardiac disease; cattle with ascites have a poor prognosis because the
      condition is usually assocaited with terminal disease. Two animals had cor
      pulmonale with chronic pneumonia, three had cardiomyopathy, one had bacterial
      endocarditis, two had thrombosis of the caudal vena cava and one had diffuse
      abdominal epithelioid mesothelioma.

PMID- 11316294
TI  - Relative efficiency of transmitting bovine spongiform encephalopathy to RIII mice
      by the oral route.

PMID- 11316295
TI  - Treatment of feline mammary fibroadenomatous hyperplasia with a progesterone
      antagonist.

PMID- 11316296
TI  - Foot-and-mouth disease outbreak.

PMID- 11316298
TI  - Ownership problems with strays.

PMID- 11316297
TI  - Foot-and-mouth disease outbreak.

PMID- 11316299
TI  - Whaling and welfare.

PMID- 11316300
TI  - Ban on fur farming.

PMID- 11316301
TI  - Congenital stationary night blindness in briards in the UK.

PMID- 11316302
TI  - RCVS council elections.

PMID- 11316303
TI  - Hypothyroidism in a dog.

PMID- 11316304
TI  - Research into canine diabetes mellitus.

PMID- 11316305
TI  - Fetal three-dimensional ultrasonography: today or tomorrow?

PMID- 11316306
TI  - Three-dimensional ultrasonography and assessment of the first-trimester fetus.
AB  - We used transvaginal three-dimensional ultrasonography to assess the first
      trimester fetus and compared the findings with contemporaneous two-dimensional
      ultrasonographic studies. Multiplanar three-dimensional ultrasonography provided
      good visualization of fetal anatomy and allowed fetal measurement and assessment
      of nuchal translucency thickness. Three-dimensional ultrasonography required
      significantly less time to perform and to interpret than two-dimensional
      ultrasonography. Three-dimensional ultrasonography is an effective means of
      assessing the first-trimester fetus and offers potential advantages over two
      dimensional ultrasonography.

PMID- 11316307
TI  - Three-dimensional multiplanar sonohysterography: comparison with conventional two
      dimensional sonohysterography and X-ray hysterosalpingography.
AB  - The objective of this study was to assess the value of combining transvaginal
      sonohysterography with three-dimensional multiplanar ultrasonography to optimize
      assessment of the uterus. To make this assessment, we compared findings on three
      dimensional sonohysterography with those on two-dimensional sonohysterography and
      X-ray hysterosalpingography. Of 20 women who underwent three-dimensional
      sonohysterography for various indications, 13 also underwent two-dimensional
      sonohysterography, and 12 had X-ray hysterosalpingography. We reviewed the 3
      types of examinations separately and compared the standard techniques with three
      dimensional sonohysterography to determine whether three-dimensional
      sonohysterography provided additional information. In 9 (69%) of 13 comparisons
      between three-dimensional sonohysterography and two-dimensional sonohysterography
      and in 11 (92%) of 12 comparisons between three-dimensional sonohysterography and
      X-ray hysterosalpingography, three-dimensional sonohysterography was
      advantageous. The coronal plane was most useful for displaying the relationship
      between lesions and the uterine cavity. Three-dimensional sonohysterography
      provided additional information compared with standard accepted techniques in the
      vast majority of women.

PMID- 11316308
TI  - Application of three-dimensional ultrasonography in the evaluation of the fetal
      heart.
AB  - The objectives of this study were to determine whether three-dimensional
      ultrasonography can provide more cardiac views than two-dimensional
      ultrasonography and to develop a standard technique. Eighteen women, 16 to 26
      weeks' gestation, were scanned with two-dimensional ultrasonography for 10
      minutes or less to obtain fetal heart views. Three-dimensional ultrasonography
      was used (< or =10 minutes) to obtain up to 4 acquisitions of the fetal heart: 4
      chamber view, left parasagittal, transverse, and longitudinal nonstandard. Views
      were later extracted from saved volume data, comparing the yields of two- and
      three-dimensional ultrasonography. The 4-chamber view was obtained in 15 (93%) of
      16 cases on both two- and three-dimensional ultrasonography. On two-dimensional
      ultrasonography, the left outflow tract was obtained in 68% of the cases; on
      three-dimensional ultrasonography, the left outflow tract was obtained in 46%
      from the 4-chamber view acquisition and in 100% from the left parasagittal
      acquisition. On two-dimensional ultrasonography, the right outflow tract was
      obtained in 68% of the cases; on three-dimensional ultrasonography, the right
      outflow tract was obtained in 86% from the 4-chamber view acquisition and in 71%
      from the left parasagittal acquisition. Aortic and ductal arches were obtained in
      12% and 18%, respectively, on two-dimensional ultrasonography. On three
      dimensional ultrasonography the aortic and ductal arches were obtained in 66% and
      86%, respectively, from the 4-chamber view acquisition and in 57% and 71%,
      respectively, from the left parasagittal acquisition. Three-dimensional
      ultrasonography permitted a greater number of cardiac views to be extracted from
      volume data than did two-dimensional ultrasonography.

PMID- 11316309
TI  - Three-dimensional quantitative echocardiographic assessment of ventricular volume
      in healthy human fetuses and in fetuses with congenital heart disease.
AB  - The purpose of this study was to evaluate the feasibility of three-dimensional
      freehand echocardiographic assessment of ventricular volumetry in healthy fetuses
      and in fetuses with congenital heart disease. The study was approved by the
      hospital institutional review board. After echocardiographic examination by
      conventional ultrasonographic equipment interfaced with a magnetic tracking
      system, three-dimensional cardiac data were collected prospectively in 57
      fetuses. Ventricular volumes were determined from three-dimensional data sets,
      and 22 fetuses with congenital heart disease were compared with 29 healthy
      fetuses. A multiple regression analysis of covariance was performed to assess
      between-group differences. Gated three-dimensional volume data sets enabled
      assessment of ventricular volumes in 51 of the 57 fetuses. Both fetuses with and
      without congenital heart disease had exponential increases in cardiac volumes
      during gestation. In fetuses with congenital heart disease and a marked
      inequality of ventricular size but no heart failure, the combined end-diastolic
      and stroke volumes of both ventricles were found to be significantly reduced
      compared with controls with no disease and fetuses with other types of congenital
      heart disease. Three-dimensional imaging can provide estimates of ventricular
      volume changes in fetal hearts with abnormal ventricular morphology that cannot
      easily be performed by two-dimensional echocardiography, and it may provide
      insight into evolving congenital heart disease.

PMID- 11316310
TI  - The transfrontal view: a new approach to the visualization of the fetal midline
      cerebral structures.
AB  - The objective of this study was to assess the feasibility of using the frontal
      suture as an acoustic window to visualize sonographically the midline cerebral
      structures (transfrontal view) in midtrimester fetuses. The study design was
      prospective and observational. In 124 healthy fetuses and in 2 fetuses with
      agenesis of the corpus callosum at 19 to 24 weeks' gestation, an attempt was made
      to obtain a transfrontal view by using transabdominal sonography. The
      transfrontal view was successfully and rapidly obtained in 110 (89%) of the
      healthy fetuses; it always provided detailed visualization of the entire corpus
      callosum, cavum septi pellucidii, third ventricle, brain stem, fourth ventricle,
      vermis cerebelli, and cisterna magna. The anatomic information was comparable
      with that obtained from a median sagittal scan obtained through the anterior
      fontanelle. In both fetuses with agenesis of the corpus callosum, the
      transfrontal view provided clear evidence of the anomaly. The transfrontal view
      is feasible in midtrimester fetuses and allows rapid demonstration of the
      cerebral midline structures and the corpus callosum in particular. It may be
      helpful in the diagnosis or exclusion of cerebral anomalies, and at least in some
      cases, it may obviate the need for a transvaginal examination. The transfrontal
      view may also be used to standardize the scanning plane for the evaluation of the
      fetal facial profile.

PMID- 11316311
TI  - Low-resistance endometrial arterial flow in the exclusion of ectopic pregnancy
      revisited.
AB  - The objective of this study was to evaluate the efficacy of endometrial arterial
      flow in the exclusion of ectopic pregnancy. From October 1997 to June 1999, 66
      women with elevated beta-human chorionic gonadotropin titers and clinical
      indications of ectopic pregnancy were evaluated by endovaginal sonography. Women
      with a gestational sac containing an embryo, a yolk sac, or both were excluded
      from the study. Doppler ultrasonography was performed in the remaining cases when
      a definite intrauterine pregnancy could not be visualized. In all cases the
      thermal index was kept to less than 1.0, consistent with as-low-as-reasonably
      achievable principles. Trophoblastic flow was defined as a resistive index of
      less than 0.6 within the endometrium. Statistical analysis was performed using a
      2-tailed t test. Twenty women had ectopic pregnancies; 33 had spontaneous
      pregnancy losses; and 13 had normal intrauterine pregnancies. A total of 29 women
      had endometrial trophoblastic flow: 11 of 13 with intrauterine pregnancies, 1 of
      20 with ectopic pregnancies, and 17 of 33 with spontaneous pregnancy losses. The
      negative predictive value for the presence of endometrial low-resistance flow for
      excluding ectopic pregnancy was 97%. The presence of low-resistance arterial
      endometrial flow can be a useful sign in diagnosing an early intrauterine
      pregnancy and decreasing the probability that an ectopic pregnancy is present,
      particularly in patients with otherwise normal ultrasonographic findings.

PMID- 11316312
TI  - Discrimination of sonographically detected breast masses using frequency shift
      color Doppler imaging in combination with age and gray scale criteria.
AB  - Frequency shift color Doppler imaging was assessed in conjunction with patient
      age and gray scale (GS) features for discriminating benign from malignant breast
      masses. Thirty-eight women with sonographically detected masses scheduled for
      biopsy were evaluated using a 6- to 13-MHz scan head, and the masses were
      delineated in ultrasonographic image volumes. Vascularity in and around each mass
      was quantified using speed-weighted pixel density (SWD). Gray scale features were
      ranked visually on a linear scale. Combinations of indices were compared with
      histologic findings (18 benign and 20 malignant). Receiver operating
      characteristic analysis ranked performance in decreasing order from the SWD-Age
      GS index, to SWD-GS, SWD-Age, Age-GS, GS criteria, SWD, and Age. At 100%
      sensitivity, SWD-Age-GS, SWD-GS, and SWD-Age discriminated benign from malignant
      masses with specificities of 94%, 89%, and 72%, respectively. These results
      indicate significant improvement in ultrasonographic discrimination of
      sonographically detected breast masses by combining the vascularity measure SWD
      with age and GS criteria.

PMID- 11316313
TI  - Patterns of fluid accumulation on screening ultrasonography for blunt abdominal
      trauma: comparison with site of injury.
AB  - The objectives of this study were to define where fluid accumulation is shown on
      screening ultrasonography after blunt abdominal trauma and to determine how fluid
      accumulation patterns are associated with the site of injury. From 1994 to 1998,
      2,693 screening examinations for blunt abdominal trauma were performed, in which
      7 regions were examined for fluid. On the basis of a preliminary analysis of
      patients with solitary injuries, all 194 patients with sonographically detected
      fluid were grouped by fluid accumulation pattern. Fluid patterns were compared
      with sites of injury. The patterns differed between hepatic and splenic injuries.
      Fluid in the left upper quadrant, in both upper quadrants, or diffusely
      distributed suggested splenic injury, whereas fluid in the right upper quadrant
      or the right upper quadrant and lower recesses suggested hepatic injury (P <
      .0001). Fluid accumulation was random after enteric injury. Patients with
      extraperitoneal injury had no fluid or had fluid focally at the injury site. The
      ability to predict the injury site on the basis of fluid patterns should expedite
      treatment of hemodynamically unstable patients with blunt abdominal trauma.

PMID- 11316314
TI  - Quantification of fluid on screening ultrasonography for blunt abdominal trauma:
      a simple scoring system to predict severity of injury.
AB  - A simple ultrasonographic method of fluid quantification, which counted the
      number of fluid recesses, was developed to predict the severity of injury after
      blunt abdominal trauma. From 1994 to 1998, 2,693 screening ultrasonographic
      examinations were performed for blunt abdominal trauma. Of this group, 2,499
      patients had a fluid score of 0 (no fluid), and 1.4% had injuries (0.4% requiring
      surgery); 110 had a score of 1 (fluid in a single examined region), and 59% had
      injuries (13% requiring surgery); 33 had a score of 2, and 85% had injuries (36%
      requiring surgery); 30 had a score of 3, and 83% had injuries (63% requiring
      surgery); and 21 had a score of 4, and 95% had injuries (81 % requiring surgery).
      Patients with scores of 3 or greater had significantly higher rates of injury (P
      < .002) and injury requiring surgery (P < .0001) than patients with lower scores.
      The ability to predict injury severity on the basis of a simple ultrasonographic
      scoring system should expedite treatment of patients with severe trauma.

PMID- 11316315
TI  - Cardiac output measurements in congenital heart disease: validation of a simple,
      portable Doppler method.
AB  - Noninvasive Doppler cardiac output measurements are clinical standards in adults
      and children. Presently, these standard Doppler methods generally require
      relatively expensive and large imaging equipment with complex signal-processing
      techniques. Thus, universal access to these important measurements has been
      limited. Simple, portable Doppler methods have been validated previously and
      applied to infants and children without cardiac disease. Nevertheless, these
      specific, inexpensive techniques have not been validated in children with complex
      congenital heart disease. Accordingly, we compared a noninvasive, suprasternal,
      non-image-guided, pulsed Doppler cardiac output with standard invasive Fick
      cardiac outputs in 20 patients (age range, 1 month to 15 years) with congenital
      heart disease. Doppler cardiac output was displayed by multiplying the mean
      velocity with an operator-selected angiographic or echographic estimate of the
      aortic diameter. The values from linear regression analysis were r = 0.96;
      Doppler cardiac output = 0.98 x Fick cardiac output - 0.08 L/min (range, 0.55
      3.10 L/min). The 95% confidence limits were less than 35% of the mean of Doppler
      and Fick cardiac outputs across the range of measurements. We conclude that
      relatively linear and accurate measurements of cardiac output can be made by this
      simple, inexpensive, portable method in selected infants and children with
      various forms of congenital heart disease.

PMID- 11316316
TI  - Carotid artery involvement in Takayasu's arteritis: evaluation of the activity by
      ultrasonography.
AB  - The purpose of this study was to investigate the ultrasonographic criteria for
      determining the activity of carotid lesions in Takayasu's arteritis. In 10
      consecutive patients, common carotid arteries with active lesions (n = 8) and
      inactive lesions (n = 9) were included in the study. The activity of the carotid
      lesions was determined on the basis of clinical and laboratory findings and
      computed tomographic scans. Special focus was placed on thickness and
      echogenicity of the involved arterial wall and outer diameter of the involved
      arterial segment. All 17 common carotid arteries evaluated showed segmental or
      diffuse circumferential thickening of the involved wall. The wall thickness was
      2.5 to 5.0 mm (mean +/- SD, 3.3 +/- 0.8 mm) in active lesions and 1.1 to 2.0 mm
      (mean, 1.6 +/- 0.4 mm) in inactive lesions. The outer diameter of the involved
      segment was 7.0 to 15.0 mm (mean, 10.0 +/- 2.4 mm) in active lesions and 4.9 to
      9.5 mm (mean, 6.8 +/- 1.4 mm) in inactive lesions. Active lesions showed
      hyperechogenicity in the full thickness of the involved wall (n = 6) or
      concentric triple layers with a hyperechoic middle layer (n = 2). Inactive
      lesions showed hyperechogenicity (n = 7) or isoechogenicity (n = 2) of the
      involved wall. One active lesion showed intramural arteries. Although precise
      measurement to tenths of a millimeter is impossible with the transducer used,
      prominent wall thickening with a maintained outer diameter in the common carotid
      artery suggests an active lesion, whereas mild wall thickening with a decreased
      outer diameter suggests an inactive lesion. Triple layers of a thickened wall
      with intramural arteries can be an ultrasonographic finding of an active lesion.

PMID- 11316317
TI  - Abdominal wall defects: two- versus three-dimensional ultrasonographic diagnosis.
AB  - We diagnosed 12 cases of abdominal wall defects. The cases diagnosed occurred in
      6 fetuses with omphalocele, 3 with gastroschisis, 2 with prune-belly syndrome,
      and 1 with pentalogy of Cantrell. Except for 1 case of gastroschisis first
      diagnosed on the basis of three-dimensional ultrasonography at 14 weeks'
      gestation, all cases were first detected by two-dimensional transabdominal
      ultrasonography and then reevaluated with three-dimensional ultrasonography using
      multiplanar and orthogonal plane modes. Although the original diagnosis was
      accurate on the basis of two-dimensional ultrasonography in 11 of 12 cases,
      additional information was obtained by three-dimensional scanning in all cases.
      Our experience suggests that in cases in which abdominal wall defects are first
      detected by two-dimensional ultrasonographic scanning, the additional information
      gained by complementary three-dimensional ultrasonographic scanning can be useful
      for more-efficient counseling and postnatal therapeutic planning.

PMID- 11316318
TI  - Three-dimensional ultrasonographic imaging in obstetrics: present and future
      applications.

PMID- 11316319
TI  - Compression repair of ruptured pseudoaneurysms guided by color Doppler
      ultrasonography: report of two cases.
AB  - Noninvasive treatment of ruptured postcatheterization pseudoaneurysms is rare. We
      report the use of ultrasonographically guided compression repair for the
      treatment of ruptured pseudoaneurysms in 2 cases. To ensure the immediate stop of
      bleeding, more compression was applied than for nonruptured pseudoaneurysms,
      regardless of flow in the femoral artery or vein, thus maximizing the
      effectiveness of this therapy. With this method, complete thrombosis of the
      pseudoaneurysm could be achieved in less than 30 minutes. In both cases,
      ultrasonographically guided compression repair was faster than the time needed to
      prepare an operating room for surgical treatment. In follow-up examinations, no
      recurrences or further complications were detected. Ultrasonographically guided
      compression repair can be used for noninvasive treatment of ruptured
      pseudoaneurysms in some cases, provided that more compression than indicated for
      nonruptured pseudoaneurysms is applied. Further clinical experience with more
      patients will be necessary to determine the exact benefits and possible
      limitations.

PMID- 11316320
TI  - Ovarian sclerosing stromal tumors: gray scale and color Doppler sonographic
      findings.
AB  - Sclerosing stromal tumors are rare benign ovarian stromal tumors, which have
      distinctive clinical and pathologic features. The tumors occur predominantly in
      the second and third decades and are histologically characterized by the
      pseudolobular pattern of the cellular and hypocellular areas, marked vascularity,
      and heterogeneity of the cellular area. We analyzed 7 cases of sclerosing stromal
      tumors, which showed a typical sonographic appearance. On sonograms, sclerosing
      stromal tumors were solid and cystic and contained multiple round or cleftlike
      cysts. Ascites was rare. On transvaginal color Doppler sonograms, sclerosing
      stromal tumors were very hypervascular in the peripheral solid area and internal
      intercystic space and showed low-impedance flow. We conclude that sclerosing
      stromal tumors should be considered in young women with menstrual irregularity
      who have hypervascular solid and cystic adnexal masses.

PMID- 11316321
TI  - Walker-Warburg syndrome: case report and review of the literature.

PMID- 11316322
TI  - Use of three-dimensional ultrasonography in differentiating craniosynostosis from
      severe fetal molding.

PMID- 11316323
TI  - Melatonin, a pineal secretory product with antioxidant properties, protects
      against cisplatin-induced nephrotoxicity in rats.
AB  - In an attempt to define the role of the pineal secretory melatonin and an
      analogue, 6-hydroxymelatonin (6-OHM), in limiting oxidative stress, the present
      study investigated the cisplatin (CP)-induced alteration in the renal antioxidant
      system and nephroprotection with the two indolamines. Melatonin (5 mg/kg), 6-OHM
      (5 mg/kg), or an equal volume of saline were administered intraperitoneally
      (i.p.) to male Sprague Dawley rats 30 min prior to an i.p. injection of CP (7
      mg/kg). After CP treatment, the animals each received indolamine or saline every
      day and were sacrificed 3 or 5 days later and plasma as well as kidney were
      collected. Both plasma creatinine and blood urea nitrogen increased significantly
      following CP administration alone; these values decreased significantly with
      melatonin co-treatment of CP-treated rats. In the kidney, CP decreased the levels
      of GSH (reduced glutathione)/GSSG (oxidized glutathione) ratio, an index directly
      related to oxidative stress. When animals were treated with melatonin, the
      reduction in the GSH/GSSG ratio was prevented. Treatment of CP-enhanced lipid
      peroxidation in the kidney was again prevented in animals treated with melatonin.
      The activity of the antioxidant enzyme, glutathione peroxidase (GSH-Px),
      decreased as a result of CP administration, which was restored to control levels
      with melatonin co-treatment. Upon histological analysis, damage to the proximal
      tubular cells was seen in the kidneys of CP-treated rats; these changes were
      prevented by melatonin treatment. 6-OHM has been shown to have some antioxidative
      capacity, however, the protective effects of 6-OHM against CP-induced
      nephrotoxicity were less than those of melatonin. The residual platinum
      concentration in the kidney of melatonin co-treated rats was significantly lower
      than that of rats treated with CP alone. It is concluded that administration of
      CP imposes a severe oxidative stress to renal tissue and melatonin confers
      protection against the oxidative damage associated with CP. This mechanism may be
      reasonably attributed to its radical scavenging activity, to its GSH-Px
      activating property, and/or to its regulatory activity for renal function.

PMID- 11316324
TI  - Expression and functional characterization of the mt1 melatonin receptor from rat
      brain in Xenopus oocytes: evidence for coupling to the phosphoinositol pathway.
AB  - Melatonin-sensitive receptors were expressed in Xenopus laevis oocytes following
      an injection of mRNA from rat brain. The administration of 0.1-100 micromol/L
      melatonin to voltage-clamped oocytes activates calcium-dependent chloride
      currents via a pertussis toxin-sensitive G protein and the phosphoinositol
      pathway. To determine which melatonin receptor type (mt1, MT2, MT3) is
      functionally expressed in the Xenopus oocytes, we used (i) agonists and
      antagonists of different receptor types to characterize the pharmacological
      profile of the expressed receptors and (ii) a strategy of inhibiting melatonin
      receptor function by antisense oligonucleotides. During pharmacological screening
      administration of the agonists 2-iodomelatonin and 2-iodo-N-butanoyl-5
      methoxytryptamine (IbMT) to the oocytes resulted in oscillatory membrane
      currents, whereas the administration of the MT3 agonist 5-methoxycarbonylamino-N
      acetyltryptamine (GR135,531) exerted no detectable membrane currents. The
      melatonin response was abolished by a preceding administration of the antagonists
      2-phenylmelatonin and luzindole but was unaffected by the MT3 antagonist prazosin
      and the MT2 antagonist 4-phenyl-2-propionamidotetralin (4-P-PDOT). In the
      antisense experiments, in the control group the melatonin response occurred in 45
      of 54 mRNA-injected oocytes (83%). Co-injection of the antisense oligonucleotide,
      corresponding to the mt1 receptor mRNA, caused a marked and significant reduction
      in the expression level (13%; P < 0.001). In conclusion, the results demonstrate
      that injection of mRNA from rat brain in Xenopus oocytes induced the expression
      of the mt1 receptor which is coupled to the phosphoinositol pathway.

PMID- 11316325
TI  - Melatonin prevents endotoxin-induced circulatory failure in rats.
AB  - The pineal secretory product melatonin was found to exert protective effects in
      septic shock. In a host infected by bacterial lipopolysaccharide (LPS), the
      expression and release of proinflammatory tumor necrosis factor-alpha (TNF-alpha)
      is rapidly increased, suggesting that TNF-alpha is associated with the etiology
      of endotoxic shock. Recent reports show that the expression of NO synthase (NOS)
      II and the production of superoxide anion (O2*-) also contribute to the
      pathophysiology of septic shock. In the present study we demonstrate that
      melatonin prevents circulatory failure in rats with endotoxemia and improves
      survival in mice treated with a lethal dose of LPS. The beneficial hemodynamic
      effects of melatonin in the endotoxemic animal appear to be associated with the
      inhibition of (i) the release of TNF-alpha in plasma, (ii) the expression of NOS
      II in liver, and (iii) the production of O2*- in aortae. In addition, the
      infiltration of polymorphonuclear neutrophils into the liver from the surviving
      LPS mice treated with melatonin was reduced. Thus, our results support the
      clinical use of melatonin in endotoxemia.

PMID- 11316326
TI  - Melatonin protects against streptozotocin, but not interleukin-1beta-induced
      damage of rodent pancreatic beta-cells.
AB  - In the present study, we examined whether melatonin can protect rodent pancreatic
      islets against streptozotocin (STZ) and interleukin-1beta (IL-1beta)-induced
      suppression of beta-cell function. Formation of free radicals, DNA damage and
      extensive DNA repair leading to depletion of intracellular nicotinamide adenine
      dinucleotide (NAD) may mediate STZ toxicity. Activation of inducible nitric oxide
      synthase and nitric oxide (NO) formation may cause IL-1beta -induced beta-cell
      impairment. We also studied the effect of melatonin against STZ-induced
      hyperglycemia in C57BL/Ks mice. For in vitro studies, cultured rat islets were
      exposed to melatonin (100 microM-1 mM) 30 min prior to STZ (0.5 mM) or IL-1beta
      (25 U/mL) addition. After an additional 30 min incubation with STZ, islet
      function and NAD content were analyzed either acutely or after 18 hr of recovery
      in fresh culture medium. For IL-1beta experiments, islets were incubated for 48
      hr with the cytokine before evaluation of islet function. We found that melatonin
      counteracted STZ-induced inhibition of glucose metabolism and insulin release in
      cultured rat islets after 18 hr of recovery. Moreover, NAD levels were higher in
      the melatonin-treated group at this time point. Melatonin had no effect on IL
      1beta-induced islet inhibition of glucose oxidation or NO formation. Diabetes
      induced by STZ (140 mg/kg body weight; i.v.) was effectively prevented by
      administration of melatonin (100 mg/kg body weight; i.p.) 30 min before STZ
      injection. We conclude that the protective effects of melatonin against beta-cell
      damage may be related to interference with DNA damage and poly(ADP-ribose)
      polymerase (PARP) activation rather than through effects on NO generation
      pathways.

PMID- 11316327
TI  - Prolonged swim-test immobility of serotonin N-acetyltransferase (AANAT)-mutant
      mice.
AB  - Serotonin N-acetyltransferase (AANAT; EC 2.3.1.87) metabolizes serotonin into N
      acetylserotonin (NAS). AANAT mRNA is expressed in the pineal gland and retina,
      and also in the rat brain. It was proposed that NAS could be a mediator of the
      antidepressant action of drugs, and it was shown that chronic but not acute
      treatment of rats with the antidepressant fluoxetine increases the content of
      AANAT mRNA in the rat hippocampus. Consequently, AANAT deficiency might be
      involved in the pathobiology of depression. C57BL/6J mice have a mutant AANAT
      gene and are considered AANAT-deficient, i.e., "knocked down" (compared with
      their normal counterparts, C3H/HeJ mice). In this study, we investigated whether
      AANAT mRNA is expressed in the brain of C57BL/6J and C3H/HeJ mice and whether
      those mice differ behaviorally, i.e., in a forced swimming test which is used to
      evaluate antidepressant drugs (such drugs shorten the time of immobility). We
      found that C3H/HeJ mice express in the brain normal AANAT mRNA, whereas C57BL/6J
      mice express mutated AANAT mRNA. The mutant, AANAT knocked down C57BL/6J mice
      displayed significantly longer times of immobility ("depression"). This
      difference was evident regardless of the circadian rhythm, i.e., both during the
      day and in the dark at night. Further studies are needed to fully characterize
      the behavioral significance of AANAT mutation and its possible link to
      depression.

PMID- 11316329
TI  - Circadian rhythm of melatonin, corticosterone and phagocytosis: effect of stress.
AB  - Melatonin has a functional connection with the immune system. Phagocyte function
      is altered by extirpation of the pineal gland, one source of melatonin, or by in
      vitro incubation of phagocytes with pharmacological concentrations of melatonin.
      Given that its synthesis by pinealocytes is under the control of the
      noradrenaline released by the sympathetic postganglionaric nerve endings, the
      present work was aimed at evaluating the circadian rhythm of melatonin,
      corticosterone, and phagocytosis in BALB/c mice in basal and stress situations.
      Peritoneal macrophages were used as phagocytes, latex beads as the particles to
      be ingested, and forced swimming to exhaustion as the stress situation.
      Radioimmunoassay was used to determine the animals' serum hormone levels. Samples
      were taken every 3 hr in the period from 04:00 to 22:00 hr, and every 30 min
      during the remaining period from 22:00 to 04:00 hr. Control mice presented a
      short-term melatonin peak at 23:30 hr, while the maximum inert-particle ingestion
      capacity of the peritoneal macrophages also occurred during the night but at
      03:30 hr. The corticosterone levels in control mice presented a circadian rhythm
      with a day-time maximum peak (16:00 hr). Compared with the controls, the animals
      subjected to stress maintained, although at lower values, the melatonin peak at
      23:30 hr, but they presented a loss of the rhythm of serum corticosterone levels,
      and the corticosterone levels and the macrophage phagocytic capacity were greater
      at all hours of the day.

PMID- 11316328
TI  - Chimeric Galphaq subunits can distinguish the long form of the Xenopus Mel1c
      melatonin receptor from the mammalian mt1 and MT2 melatonin receptors.
AB  - The family of melatonin receptors is composed of the mt1, MT2, and Mel1c
      subtypes. The Mel1c is further divided into one long and two short isoforms. A
      recent study has shown that, unlike mt1 and MT2, the long form of Mel1c is
      incapable of activating the pertussis toxin-insensitive G16. Here we used three
      well-characterized Galphaq chimeras to explore the coupling specificity of the
      melatonin receptors. The qi5, qo5, and qz5 chimeras can link numerous Gi-coupled
      receptors to the stimulation of phosphoinositide-specific phospholipase C. Both
      mt1 and MT2 receptors interacted productively with the Galphaq chimeras, while
      the long form of Mel1c was totally ineffective. Among the Galphaq chimeras, qo5
      was less efficiently coupled to the melatonin receptors. Such differential
      coupling is best explained by structural differences between the melatonin
      receptors as well as among the Galphaq chimeras. Since the long form of Mel1c
      receptor possesses an exceptionally large C-terminal tail, we tested the ability
      of four melatonin receptor C-terminal tail chimeras (Chi 1-4) to interact with
      the Galphaq chimeras. The presence of the large C-terminal tail of Mel1c in Chi 1
      and Chi 3 markedly hindered their coupling to the Galphaq chimeras. On the other
      hand, the attachment of either the mtl or MT2 C-terminal tail to a Mel1c backbone
      produced chimeras (Chi 2 and Chi 4) that were capable of activating the Galphaq
      chimeras. These findings suggest the involvement of C-terminal regions of
      melatonin receptors in the recognition of G proteins.

PMID- 11316330
TI  - The impact of fetal size and length of gestation on 6-sulphatoxymelatonin
      excretion in adult life.
AB  - Recent studies have shown that intrauterine growth retardation or fetal distress
      in human infants is associated with a pronounced reduction in melatonin secretion
      during the first 3 months of life. It is not known whether these associations
      persist beyond infancy. We have therefore examined the relationship between
      birthsize and melatonin secretion in 159 men and women aged 20, born in Adelaide,
      South Australia. Melatonin secretion was estimated by analysing the overnight
      urinary excretion of 6-sulphatoxymelatonin. The overnight excretion ranged from
      1.7 to 128.9 nmoles/subject, was higher in women than in men (46.5 vs 34.1
      nmoles, P = 0.003) and was significantly negatively correlated with the body mass
      index (P = 0.006). Excretion correlated with both birthweight and ponderal index
      at birth (P = 0.04 and P = 0.01 respectively after adjustment for gestational
      age) and also fell with increased duration of gestation (P = 0.007). The effects
      of adult body mass index added to that of low birthweight in predicting 6
      sulphatoxymelatonin excretion. These data suggest that urinary 6
      sulphatoxymelatonin excretion was impaired in adults who were growth restricted
      prenatally or were delivered after 40 weeks gestation.

PMID- 11316331
TI  - Parental anxiety disorders, child anxiety disorders, and the perceived parent
      child relationship in an Australian high-risk sample.
AB  - This study was designed to explore the role of perceived parenting behavior in
      the relationship between parent and offspring anxiety disorders in a high-risk
      sample of adolescents. We examined the relationship between parental and child
      anxiety disorders and tested whether perceived parenting behavior acted as a
      mediator between these variables. Analyses were performed on a high-risk sample
      of 816 fifteen-year-olds drawn from a birth cohort in Queensland, Australia.
      Parental depression and income were covaried. Maternal anxiety disorder
      significantly predicted the presence of anxiety disorders in children; the
      association between paternal anxiety disorder and child anxiety disorder was not
      significant. There was no evidence that perceived parenting played a mediating
      role in the association between mother and child anxiety disorders. These results
      replicate earlier studies' findings of elevated rates of anxiety disorders among
      the offspring of anxious parents, but only when the child's mother is the anxious
      parent.

PMID- 11316332
TI  - Autonomy and relatedness in family interactions with depressed adolescents.
AB  - This study investigated family interaction patterns associated with adolescent
      depression. Twenty adolescent-mother dyads with clinically depressed adolescents
      participated in the study. Twenty dyads with externalizing youths and 20
      nonclinic dyads were included as controls. Dimensions of autonomy and relatedness
      were rated during a videotaped mother-adolescent problem-solving task. Adolescent
      perceptions of parent attachment were also evaluated. Results indicated that
      depressed adolescents and their mothers did not differ in their behavior compared
      with nonclinic adolescents. Dyads with externalizing adolescents showed the
      highest impairment in autonomy and relatedness. Depressed adolescents perceived
      the quality of their relationships with their parents to be impaired relative to
      nonclinic dyads, as did externalizing adolescents.

PMID- 11316333
TI  - Depression and self-esteem in boys with attention-deficit/hyperactivity disorder:
      associations with comorbid aggression and explanatory attributional mechanisms.
AB  - It was tested whether boys with attention-deficit/hyperactivity disorder (ADHD),
      subgrouped by aggressive status, would show higher rates of depressive
      symptomatology and lower levels of self-esteem than would comparison boys and, in
      a subsample, explored attributional mechanisms that may be related to such
      internalizing features. Study 1 utilized 114 boys with ADHD (all prior recipients
      of stimulant medication) and 87 comparison boys, aged 7-12 years. Aggressive boys
      with ADHD reported more symptoms of depression than did nonaggressive boys with
      ADHD, who, in turn, reported more depression than did comparison boys. Effect
      sizes were moderate to large and did not vary with a depression rating scale
      uncontaminated by ADHD-related items. For self-esteem, the most pronounced effect
      was that aggressive boys with ADHD showed lower levels than did nonaggressive
      ADHD or comparison boys; effects were again moderate to large. Study 2
      participants were a subsample of boys with ADHD from Study 1 (N = 27). We probed
      causal attributions in ADHD-related domains through responses to hypothetical
      vignettes, in which the protagonist's medication status (medicated, not
      medicated) was crossed with type of outcome (good, bad). Medication-related
      attributions were frequent. In describing the protagonist's success in relation
      to medication treatment, the sample showed significant associations between (a)
      medication-related attributions and (b) increased depressive symptomatology as
      well as decreased self-esteem. We discuss attributional processes that may help
      to explain the variation in internalizing symptoms among children with ADHD.

PMID- 11316334
TI  - Conceptions of relationships in children with depressive and aggressive symptoms:
      social-cognitive distortion or reality?
AB  - This research tested skill-deficit and cognitive-distortion models of depression
      and aggression in 615 fifth- and sixth-grade children. Children completed a
      measure of their generalized conceptions of relationships in the peer domain and
      their level of depressive symptoms. Teachers completed measures of social
      competence, social status, and aggression. As anticipated, children with higher
      levels of depressive symptoms, either alone or in combination with aggression,
      demonstrated more negative conceptions of both self and peers than did
      nonsymptomatic children. Conceptions of relationships did not differentiate
      between aggressive and nonsymptomatic children. Children with depressive symptoms
      and children with aggressive symptoms displayed unique profiles of social
      competence deficits and problematic status in the peer group. Analysis of the
      accuracy of children's conceptions of relationships revealed support for both
      skill-deficit and cognitive-distortion models. Consistent with a skill-deficit
      model, children with depressive and depressive-aggressive symptoms were sensitive
      to actual differences in their social status. In contrast, aggressive children
      showed an insensitivity to social cues. Consistent with a cognitive-distortion
      model, children with depressive and depressive-aggressive symptoms had more
      negative conceptions than would be expected given their social status, whereas
      aggressive-unpopular children demonstrated a self-enhancement bias. These
      findings indicate the importance of integrated cognitive-interpersonal models of
      depression and aggression that incorporate multiple pathways among social
      cognitive, interpersonal, and emotional functioning.

PMID- 11316335
TI  - Externalizing symptomatology among adoptive youth: prevalence and preadoption
      risk factors.
AB  - The extent of symptomatology related to attention-deficit hyperactivity disorder
      (ADHD) and oppositional defiant disorder (ODD) was examined in a statewide sample
      of adopted youth, aged 4-18 years (n = 808). The use of normed questionnaires in
      a nonclinical sample decreased biases associated with past research on adopted
      children. According to parental report, a striking number of the youth qualified
      as manifesting significant symptom levels of externalizing behavior problems: 21%
      met symptom cutoffs for ADHD (with or without ODD) and 20% met criteria for ODD
      (with or without ADHD), for a combined total of 29% of the sample. A number of
      parent-reported, preadoptive risk factors distinguished these groups from one
      another and from the nonexternalizing youth. The clearest associated factors
      included histories of preadoption abuse/neglect, later age of adoption, prenatal
      drug exposure, and placement in multiple foster homes prior to adoption. We
      discuss implications regarding both etiology and current controversies
      surrounding the disproportionate levels of behavioral difficulties in adopted
      youth.

PMID- 11316336
TI  - Factor structure and criterion validity of secondary school teacher ratings of
      ADHD and ODD.
AB  - Attention-Deficit Hyperactivity Disorder (ADHD) is currently viewed as a
      heterogeneous disorder with two factors: inattention and impulsivity
      hyperactivity. This conceptualization of ADHD is based primarily on research with
      children or samples that mix children and adolescents. To examine if the 2-factor
      ADHD model is appropriate for adolescents and if the ADHD factors are distinct
      from Oppositional Defiant Disorder (ODD) in adolescents, teacher rating data were
      collected for 2 samples of adolescents. The results of a confirmatory factor
      analysis supported the convergent and divergent validity of a model with separate
      but correlated factors for inattention, impulsivity-hyperactivity, and defiant
      behavior. Further evidence of construct validity was found when factor scores
      were examined relative to the criterion variables of academic performance and
      rule-breaking behavior. The results support the utility of teacher ratings of
      ADHD and ODD in the assessment of adolescents, and the applicability of the DSM
      IV conceptualization of these disorders to adolescents.

PMID- 11316337
TI  - The Child Behavior Checklist for group care workers: a study regarding the factor
      structure.
AB  - In this study we examined the factor structure of the Child Behavior Checklist
      (CBCL) filled out by group care workers. Group care workers' judgements were
      collected on 846 children and adolescents treated in various residential settings
      in The Netherlands. Using confirmatory factor analysis, we were able to show that
      the original CBCL factor model based on parental judgments of child behavior also
      fits for the judgments of group care workers. This means that the well known 8
      narrow-band syndromes (Withdrawn, Somatic Complaints, etc.) as well as the 2
      broad-band syndromes (Internalizing and Externalizing) can be used to interpret
      the CBCL scores of group care workers. This confirmation of the CBCL factor
      structure is a first step to add a group care worker version to the CBCL family.
      However, as a second step, normative data need to be gathered to further enhance
      the use of the CBCL for group care workers.

PMID- 11316338
TI  - Spike-frequency adaptation of a generalized leaky integrate-and-fire model
      neuron.
AB  - Although spike-frequency adaptation is a commonly observed property of neurons,
      its functional implications are still poorly understood. In this work, using a
      leaky integrate-and-fire neural model that includes a Ca2+-activated K+ current
      (IAHP), we develop a quantitative theory of adaptation temporal dynamics and
      compare our results with recent in vivo intracellular recordings from pyramidal
      cells in the cat visual cortex. Experimentally testable relations between the
      degree and the time constant of spike-frequency adaptation are predicted. We also
      contrast the IAHP model with an alternative adaptation model based on a dynamical
      firing threshold. Possible roles of adaptation in temporal computation are
      explored, as a a time-delayed neuronal self-inhibition mechanism. Our results
      include the following: (1) given the same firing rate, the variability of
      interspike intervals (ISIs) is either reduced or enhanced by adaptation,
      depending on whether the IAHP dynamics is fast or slow compared with the mean ISI
      in the output spike train; (2) when the inputs are Poisson-distributed
      (uncorrelated), adaptation generates temporal anticorrelation between ISIs, we
      suggest that measurement of this negative correlation provides a probe to assess
      the strength of IAHP in vivo; (3) the forward masking effect produced by the slow
      dynamics of IAHP is nonlinear and effective at selecting the strongest input
      among competing sources of input signals.

PMID- 11316339
TI  - Information-theoretic analysis of neural coding.
AB  - We describe an approach to analyzing single- and multiunit (ensemble) discharge
      patterns based on information-theoretic distance measures and on empirical
      theories derived from work in universal signal processing. In this approach, we
      quantify the difference between response patterns, whether time-varying or not,
      using information-theoretic distance measures. We apply these techniques to
      single- and multiple-unit processing of sound amplitude and sound location. These
      examples illustrate that neurons can simultaneously represent at least two kinds
      of information with different levels of fidelity. The fidelity can persist
      through a transient and a subsequent steady-state response, indicating that it is
      possible for an evolving neural code to represent information with constant
      fidelity.

PMID- 11316340
TI  - Model of familiarity discrimination in the perirhinal cortex.
AB  - Much evidence indicates that recognition memory involves two separable processes,
      recollection and familiarity discrimination, with familiarity discrimination
      being dependent on the perirhinal cortex of the temporal lobe. Here, we describe
      a new neural network model designed to mimic the response patterns of perirhinal
      neurons that signal information concerning the novelty or familiarity of stimuli.
      The model achieves very fast and accurate familiarity discrimination while
      employing biologically plausible parameters and Hebbian learning rules. The fact
      that the activity patterns of the model's simulated neurons are closely similar
      to those of neurons recorded from the primate perirhinal cortex indicates that
      this brain region could discriminate familiarity using principles akin to those
      of the model. If so, the capacity of the model establishes that the perirhinal
      cortex alone may discriminate the familiarity of many more stimuli than current
      neural network models indicate could be recalled (recollected) by all the
      remaining areas of the cerebral cortex. This efficiency and speed of detecting
      novelty provides an evolutionary advantage, thereby providing a reason for the
      existence of a familiarity discrimination network in addition to networks used
      for recollection.

PMID- 11316341
TI  - Brain size and number of neurons: an exercise in synthetic neuroanatomy.
AB  - Certain remarkable invariances have long been known in comparative neuroanatomy,
      such as the proportionality between neuronal density and the inverse of the cubic
      root of brain volume or that between the square root of brain weight and the
      cubic root of body weight. Very likely these quantitative relations reflect some
      general principles of the architecture of neuronal networks. Under the assumption
      that most of brain volume is due to fibers, we propose four abstract models: I,
      constant fiber length per neuron; II, fiber length proportionate to brain
      diameter; III, complete set of connections between all neurons; IV, complete set
      of connections between compartments each containing the square root of the total
      number of neurons. Model I conforms well to the cerebellar cortex. Model II
      yields the observed comparative invariances between number of neurons and brain
      size. Model III is totally unrealistic, while Model IV is compatible with the
      volume of the hemispheric white substance in different mammalian species.

PMID- 11316342
TI  - Membrane potential fluctuations determine the precision of spike timing and
      synchronous activity: a model study.
AB  - It is much debated on what time scale information is encoded by neuronal spike
      activity. With a phenomenological model that transforms time-dependent membrane
      potential fluctuations into spike trains, we investigate constraints for the
      timing of spikes and for synchronous activity of neurons with common input. The
      model of spike generation has a variable threshold that depends on the time
      elapsed since the previous action potential and on the preceding membrane
      potential changes. To ensure that the model operates in a biologically meaningful
      range, the model was adjusted to fit the responses of a fly visual interneuron to
      motion stimuli. The dependence of spike timing on the membrane potential dynamics
      was analyzed. Fast membrane potential fluctuations are needed to trigger spikes
      with a high temporal precision. Slow fluctuations lead to spike activity with a
      rate about proportional to the membrane potential. Thus, for a given level of
      stochastic input, the frequency range of membrane potential fluctuations induced
      by a stimulus determines whether a neuron can use a rate code or a temporal code.
      The relationship between the steepness of membrane potential fluctuations and the
      timing of spikes has also implications for synchronous activity in neurons with
      common input. Fast membrane potential changes must be shared by the neurons to
      produce synchronous activity.

PMID- 11316344
TI  - Development of a brief measure to assess quality of life in obesity.
AB  - OBJECTIVE: Obesity researchers have a growing interest in measuring the impact of
      weight and weight reduction on quality of life. The Impact of Weight on Quality
      of Life questionnaire (IWQOL) was the first self-report instrument specifically
      developed to assess the effect of obesity on quality of life. Although the IWQOL
      has demonstrated excellent psychometric properties, its length (74 items) makes
      it somewhat cumbersome as an outcome measure in clinical research. This report
      describes the development of a 31-item version of the IWQOL (IWQOL-Lite).
      RESEARCH METHODS AND PROCEDURES: IWQOLs from 996 obese patients and controls were
      used to develop the IWQOL-Lite. Psychometric properties of the IWQOL-Lite were
      examined in a separate cross-validation sample of 991 patients and controls.
      RESULTS: Confirmatory factor analysis provided strong support for the adequacy of
      the scale structure. The five identified scales of the IWQOL-Lite (Physical
      Function, Self-Esteem, Sexual Life, Public Distress, and Work) and the total
      IWQOL-Lite score demonstrated excellent psychometric properties. The reliability
      of the IWQOL-Lite scales ranged from 0.90 to 0.94 and was 0.96 for the total
      score. Correlations between the IWQOL-Lite and collateral measures supported the
      construct validity of the IWQOL-Lite. Changes in IWQOL-Lite scales over time
      correlated significantly with changes in weight, supporting its sensitivity to
      change. Significant differences in IWQOL-Lite scale and total scores were found
      among groups differing in body mass index, supporting the utility of the IWQOL
      Lite across the body mass index spectrum. DISCUSSION: The IWQOL-Lite appears to
      be a psychometrically sound and clinically sensitive brief measure of quality of
      life in obese persons.

PMID- 11316345
TI  - Obesity-related knowledge, attitudes, and behaviors in obese and non-obese urban
      Philadelphia female adolescents.
AB  - OBJECTIVES: To examine relationships between knowledge, attitudinal and
      behavioral factors, and obesity and to determine how these factors influence
      obesity status in west Philadelphia female adolescents. RESEARCH METHODS AND
      PROCEDURES: A matched-pairs study was conducted with 32 stature- and age-matched
      pairs of obese (body mass index and triceps skinfold > or =95th percentile of
      National Health and Nutrition Examination Survey I) and non-obese (body mass
      index and triceps skinfold between the 15th and 85th percentiles of National
      Health and Nutrition Examination Survey I) female African American adolescents
      (aged 11 to 15 years), selected from a school-based study sample, based on
      obesity status and matching criteria. Adolescents were compared on the following
      measures: physical activity, inactivity, dietary intake, eating attitudes, health
      behavior knowledge, body image, self-esteem, and maturation status. Differences
      between obese and non-obese females were tested using paired t tests and Wilcoxon
      matched-pairs signed-rank tests. RESULTS: Physical activity, inactivity, and
      perception of ideal body size emerged as the most important contributory factors
      to obesity status. There were no statistically significant matched-pair
      differences in macronutrient and micronutrient intakes, self-esteem, eating
      attitudes, health behavior knowledge, or maturation status of these adolescents.
      Obese adolescents had significantly lower levels of physical activity, higher
      inactivity, and a larger perception of ideal body size than non-obese
      adolescents. DISCUSSION: Knowledge and attitudinal factors (with the exception of
      perception of ideal body size) had far less association with obesity than
      activity-related behavioral factors. These findings suggest that future
      intervention strategies should pay particular attention to physical activity,
      inactivity, and body image attitudes.

PMID- 11316343
TI  - Osmotic forces and gap junctions in spreading depression: a computational model.
AB  - In a computational model of spreading depression (SD), ionic movement through a
      neuronal syncytium of cells connected by gap junctions is described
      electrodiffusively. Simulations predict that SD will not occur unless cells are
      allowed to expand in response to osmotic pressure gradients and K+ is allowed to
      move through gap junctions. SD waves of [K+]out approximately 25 to approximately
      60 mM moving at approximately 2 to approximately 18 mm/min are predicted over the
      range of parametric values reported in gray matter, with extracellular space
      decreasing up to approximately 50%. Predicted waveform shape is qualitatively
      similar to laboratory reports. The delayed-rectifier, NMDA, BK, and Na+ currents
      are predicted to facilitate SD, while SK and A-type K+ currents and glial
      activity impede SD. These predictions are consonant with recent findings that gap
      junction poisons block SD and support the theories that cytosolic diffusion via
      gap junctions and osmotic forces are important mechanisms underlying SD.

PMID- 11316346
TI  - The adipose tissue phenotype of hormone-sensitive lipase deficiency in mice.
AB  - OBJECTIVE: To directly ascertain the physiological roles in adipocytes of hormone
      sensitive lipase (HSL; E.C. 3.1.1.3), a multifunctional hydrolase that can
      mediate triacylglycerol cleavage in adipocytes. RESEARCH METHODS AND PROCEDURES:
      We performed constitutive gene targeting of the mouse HSL gene (Lipe),
      subsequently studied the adipose tissue phenotype clinically and histologically,
      and measured lipolysis in isolated adipocytes. RESULTS: Homozygous HSL-/- mice
      have no detectable HSL peptide or cholesteryl esterase activity in adipose
      tissue, and heterozygous mice have intermediate levels with respect to wild-type
      and deficient littermates. HSL-deficient mice have normal body weight but reduced
      abdominal fat mass compared with normal littermates. Histologically, both white
      and brown adipose tissues in HSL-/- mice show marked heterogeneity in cell size,
      with markedly enlarged adipocytes juxtaposed to cells of normal morphology. In
      isolated HSL-/- adipocytes, lipolysis is not significantly increased by beta3
      adrenergic stimulation, but under basal conditions in the absence of added
      catecholamines, the lipolytic rate of isolated HSL-/- adipocytes is at least as
      high as that of cells from normal controls. Cold tolerance during a 48-hour
      period at 4 degrees C was similar in HSL-/- mice and controls. Overnight fasting
      was well-tolerated clinically by HSL-/- mice, but after fasting, liver
      triglyceride content was significantly lower in HSL-/- mice compared with wild
      type controls. CONCLUSIONS: In isolated fat cells, the lipolytic rate after beta
      adrenergic stimulation is mainly dependent on HSL. However, the observation of a
      normal rate of lipolysis in unstimulated HSL-/- adipocytes suggests that HSL
      independent lipolytic pathway(s) exist in fat. Physiologically, HSL deficiency in
      mice has a modest effect under normal fed conditions and is compatible with
      normal maintenance of core body temperature during cold stress. However, the
      lipolytic response to overnight fasting is subnormal.

PMID- 11316347
TI  - Conjugated linoleic acid (CLA), body fat, and apoptosis.
AB  - OBJECTIVE: The objective of the study was to determine if consumption of
      conjugated linoleic acid (CLA) by mice could induce apoptosis in adipose tissue.
      Other objectives were to determine the influence of feeding mice CLA for < or =2
      weeks on body fat, energy expenditure, and feed intake. RESEARCH METHODS AND
      PROCEDURES: A mixture of CLA isomers (predominantly c9,t11 and t10,c12) was
      included in the AIN-93G diet at 0, 1, and 2%, and fed to mice for 12 days (Trial
      1), or was included at 2% and fed to mice for 0, 5, and 14 days (Trial 2). Feed
      intake was measured daily and energy expenditure was determined by direct
      calorimetry on day 9 in Trial 1. Retroperitoneal fat pads were analyzed for
      apoptosis by determination of DNA fragmentation. RESULTS: Dietary CLA reduced
      feed intake by 10% to 12% (p < 0.01), but either did not influence or did not
      increase energy expenditure as indicated by heat loss. Body weight was not
      influenced by consumption of CLA in Trial 1 but was increased (p < 0.01) by CLA
      in Trial 2. Weights of retroperitoneal, epididymal, and brown adipose tissues
      were lower (p < 0.01) in animals fed CLA, although liver weight was increased (p
      < 0.10; Trial 1) or not changed (Trial 2). Analysis of retroperitoneal fat pad
      DNA from both trials indicated that apoptosis was increased (p < 0.01) by CLA
      consumption. DISCUSSION: These results are interpreted to indicate that CLA
      consumption causes apoptosis in white adipose tissue. This effect occurs within 5
      days of consuming a diet that contains CLA.

PMID- 11316348
TI  - The human obesity gene map: the 2000 update.
AB  - This report constitutes the seventh update of the human obesity gene map
      incorporating published results up to the end of October 2000. Evidence from the
      rodent and human obesity cases caused by single-gene mutations, Mendelian
      disorders exhibiting obesity as a clinical feature, quantitative trait loci
      uncovered in human genome-wide scans and in cross-breeding experiments in various
      animal models, and association and linkage studies with candidate genes and other
      markers are reviewed. Forty-seven human cases of obesity caused by single-gene
      mutations in six different genes have been reported in the literature to date.
      Twenty-four Mendelian disorders exhibiting obesity as one of their clinical
      manifestations have now been mapped. The number of different quantitative trait
      loci reported from animal models currently reaches 115. Attempts to relate DNA
      sequence variation in specific genes to obesity phenotypes continue to grow, with
      130 studies reporting positive associations with 48 candidate genes. Finally, 59
      loci have been linked to obesity indicators in genomic scans and other linkage
      study designs. The obesity gene map reveals that putative loci affecting obesity
      related phenotypes can be found on all chromosomes except chromosome Y. A total
      of 54 new loci have been added to the map in the past 12 months and the number of
      genes, markers, and chromosomal regions that have been associated or linked with
      human obesity phenotypes is now above 250. Likewise, the number of negative
      studies, which are only partially reviewed here, is also on the rise.

PMID- 11316349
TI  - QT dispersion in uncomplicated human obesity.
AB  - OBJECTIVE: Because obese patients generally may be prone to ventricular
      arrhythmias, this study was designed to measure the interval between Q- and T
      waves of the electrocardiogram (QT) interval dispersion (QTD) in uncomplicated
      overweight and obese patients. QTD is an electrocardiographic parameter whose
      prolongation is thought to be predictive of the possibility of sudden death
      caused by ventricular arrhythmias. To better evaluate the association between
      obesity per se and QTD, the study population was intentionally selected because
      they were free of complications. RESEARCH METHODS AND PROCEDURES: QTD (defined as
      the difference between the maximum and the minimum QT corrected interval [QTc]
      across the 12-lead electrocardiogram) was measured manually in 54 obese patients
      (Group A: mean body mass index [BMI] of 38.1 +/- 0.9 kg/m2 [SEM], 15 males and 39
      females), 35 overweight patients (Group B: mean BMI of 27.3 +/- 0.2 kg/m2, 10
      males and 25 females), and 57 normal weight healthy control subjects (Group C:
      mean BMI of 21.9 +/- 0.2 kg/m2, 17 males and 40 females). The obese and
      overweight patients had no heart disease, hypertension, diabetes, or impaired
      glucose tolerance and did not have any hormonal, hepatic, renal or electrolyte
      disorders. The study subjects were matched in terms of age (mean age 38.4 +/- 1.2
      years) and sex. RESULTS: The QTDs were comparable among the three groups: Group
      A, 56.4 +/- 2.6 ms; Group B, 56.7 +/- 2.1 ms; and Group C, 59.4 +/- 2.1 ms; not
      significant. The QTc intervals of Group A and Group B were similar to that of
      Group C (411.8 +/- 3.3, 407.2 +/- 3.9, and 410.3 +/- 3.9 ms, respectively [not
      significant]) and did not correlate with BMI. An association was found between
      QTD and QTc (r = 0.24, p < 0.005). Using multivariate stepwise regression
      analysis of the study population, QTD did not correlate with age, BMI, waist
      circumference, or abdominal sagittal diameter. DISCUSSION: These data suggest
      that QTD in uncomplicated obese or overweight subjects is comparable with that in
      age- and sex-matched normal weight healthy controls. In this study population, no
      association was found between QTD and anthropometric parameters reflecting body
      fat distribution.

PMID- 11316350
TI  - Comparison of thermogenic sympathetic response to food intake between obese and
      non-obese young women.
AB  - OBJECTIVE: Sympathetic nervous system abnormality in humans is still a matter of
      debate. The present study was designed to examine diet-induced autonomic nervous
      system activity and metabolic change in obese and non-obese young women. RESEARCH
      METHODS AND PROCEDURES: Sixteen age- and height-matched obese and non-obese young
      women participated in this study. Sympathovagal activities were assessed by means
      of our newly developed spectral analysis procedure of heart-rate variability
      during the resting condition and after mixed-food ingestion (480 kcal). Energy
      expenditure was also measured under these two conditions. RESULTS: There was no
      significant difference in any of the parameters of the heart-rate variability
      between the obese group and control group during the resting condition. In the
      control group, both absolute values (221.5 +/- 54.5 vs. 363.8 +/- 43.7 ms2, p <
      0.05) and relative values (0.23 +/- 0.03 to 0.36 +/- 0.02, p < 0.05) of a very
      low-frequency component and global sympathetic nervous system index (1.46 +/-
      0.19 vs. 3.26 +/- 0.61, p < 0.05) were significantly increased after mixed-food
      ingestion compared with the values obtained after resting condition. However, no
      such sympathetic response was found in the obese group. Energy expenditure
      increased in the two groups after the meal, but the magnitude of the increase
      above the preprandial resting condition was significantly greater in the control
      group than in the obese group (11.2 +/- 2.3 vs. 6.7 +/- 0.8%, p < 0.05).
      DISCUSSION: Our data suggest that despite identical sympathovagal activities at
      the resting condition, obese young women may possess a reduced sympathetic
      response to physiological perturbation such as mixed food intake, which might be
      related to lowered capacity of thermogenesis and the state of obesity.

PMID- 11316351
TI  - The effect of low-intensity exercise training on fat metabolism of obese women.
AB  - OBJECTIVE: Previous studies have shown that fat metabolism is different in upper
      body (UB) and lower body (LB) obese women. The present study investigated whether
      the effect of low-intensity exercise training on fat metabolism is different in
      UB and LB obese premenopausal women. RESEARCH METHODS AND PROCEDURES: Twenty-one
      healthy, premenopausal women with either LB obesity (waist-to-hip ratio of < or
      =0.79; n = 8) or UB obesity (waist-to-hip ratio of > or =0.85; n = 13)
      participated in the present study. The UB obese women were matched and randomly
      divided in an exercise training group (UB) and a nonexercising control group (UB
      C). Subjects in the UB and LB groups participated in a low-intensity exercise
      training program (40% VO2max) three times per week for 12 weeks. Before and after
      the intervention, measurements of fat metabolism at rest and during exercise,
      body composition, and maximal aerobic capacity were performed. RESULTS: Exercise
      training did not change the respiratory exchange ratio at rest in the UB and LB
      groups. During exercise, relative fat oxidation increased in the UB group by 19%
      (p < 0.05), whereas no change in the LB and UB-C groups was found. Plasma free
      fatty acid oxidation did not change by exercise training, and nonplasma fatty
      acid oxidation tended to increase in the UB group compared with the UB-C group (p
      = 0.08). DISCUSSION: Low-intensity exercise training increased the contribution
      of fat oxidation to total energy expenditure during exercise but not at rest in
      UB obese women. Exercise training had no significant effect on fat metabolism in
      the LB obese women.

PMID- 11316352
TI  - Prediction of body fat by anthropometry in older Chinese people.
AB  - OBJECTIVE: To derive regression equations for fat percentage by using simple
      anthropometric measurements applicable in normal and immobile (cannot stand or
      walk) older people. RESEARCH METHODS AND PROCEDURES: The study population
      comprised 352 females and 261 males, apparently well and community-dwelling, aged
      69 to 82 years. Fifty-one females and 27 males were recruited for external
      validation. Body weight, standing height, arm span, triceps and biceps skinfold
      thicknesses (SFTs), and midarm circumference were measured. The reference method
      of total body fat percentage was dual-energy X-ray densitometry. Predictive
      equations for fat percentages were derived by stepwise multiple linear regression
      on anthropometric indices and gender. RESULTS: Upper-limb SFTs, body mass index,
      and gender yielded the more predictive equation. The SEE was 4.1% weight. There
      was a significant trend of underestimation in overweight subjects, especially in
      females. The equation using SFTs and midarm circumference was less reliable but
      more applicable to older immobile people and those with significant
      kyphoscoliosis. CONCLUSIONS: The combination of body mass index and upper-limb
      SFTs gives reliable prediction of fat percentages in older Chinese people, except
      in the obese.

PMID- 11316353
TI  - Role of scintigraphy in musculoskeletal and spinal infections.
AB  - Clinical findings are still the mainstay for suspecting the diagnosis of
      musculoskeletal infections, especially osteomyelitis. No single complementary
      imaging technique has 100% specificity and sensitivity for every case of
      musculoskeletal infection. Depending on the age of the patient, presence of
      orthopedic hardware, location of infection, underlying bone, and systemic
      conditions, the choice of imaging modalities must be tailored to the patient's
      condition. Plain radiographs are performed first and may be sufficient. In
      children, bone scan is highly accurate to diagnose osteomyelitis. Labeled
      leukocytes with complementary bone or bone marrow studies are recommended for
      orthopedic hardware or diabetic foot. Finally, gallium scanning is useful for the
      diagnosis of vertebral osteomyelitis. Current radiopharmaceuticals used for
      diagnosing infection also label inflammation. Newer products, as Infecton, should
      in the future allow better differentiation between infection and sterile
      inflammation.

PMID- 11316354
TI  - Role of ultrasound in musculoskeletal infections.
AB  - Ultrasound is able to play a key role in the management of musculoskeletal soft
      tissue infections. It is an easily accessible imaging modality that can be used
      immediately after plain radiographs have been obtained. Quick diagnosis is
      essential in the clinical setting of musculoskeletal infection because delay can
      lead to significant morbidity. In addition to its diagnostic capabilities, US
      offers a safe, real-time, and convenient technique to perform immediately a
      guided-needle aspiration of any suspicious fluid collection. US provides the most
      efficient way to document quickly an infection of the musculoskeletal soft
      tissues and to identify the offending micro-organism.

PMID- 11316355
TI  - Imaging of pyogenic infectious spondylodiskitis.
AB  - The presence of infectious spondylodiskitis and its complications may present
      protean clinical and imaging findings. The frequent use of multi-imaging
      modalities has led to a greater sensitivity and specificity in the diagnosis of
      this ubiquitous disease.

PMID- 11316356
TI  - Imaging of spinal infections in children.

PMID- 11316357
TI  - Imaging of osteomyelitis in the mature skeleton.
AB  - Diagnosis of acute osteomyelitis is often challenging but can be made by plain
      radiograph, bone scan, or MR imaging. This diagnosis may be more problematic in
      small bones, in diabetic or immunocompromised patients, those partially treated,
      post-traumatic, previous surgery, or with pre-existing marrow conditions and
      associated soft tissue infections. CT is the modality of choice for revealing
      sequestra and cortical erosions in chronic osteomyelitis. Nonenhanced and
      enhanced STIR or fat-saturated sequences are essential to reveal the marrow
      abnormality and its extension for diagnosis of subtle cases with neuropathic or
      other associated conditions. Combined radionuclide scintigraphy becomes necessary
      in complicated situations.

PMID- 11316358
TI  - Imaging of osteomyelitis in children.
AB  - Imaging approach to osteomyelitis in children should aim toward a timely and
      accurate diagnosis in view of the need for prompt therapy to prevent sequelae.
      One must take advantage of the specific value of each imaging modality and adopt
      a strategy that works best for a given child in a given institution.

PMID- 11316359
TI  - Imaging of infectious arthritis.

PMID- 11316360
TI  - Imaging of soft tissue infections.

PMID- 11316361
TI  - Imaging of chronic recurrent multifocal osteomyelitis.
AB  - The disease of CRMO is a "great clinical and radiologic mimic. There are no
      specific clinical or laboratory findings and no pathognomonic imaging or
      pathologic features have been described. Because the disease is not well known by
      clinician, radiologist, and pathologist alike, it is likely to be more common
      than the literature implies. It has been suggested that the diagnosis of CRMO
      requires an interdisciplinary team approach dependent on the cooperation of the
      pediatrician, orthopedic surgeon, pathologist, and microbiologist. We strongly
      advocate the addition of the radiologist to this list. We believe that it is the
      informed radiologist who frequently suggests the correct diagnosis.

PMID- 11316362
TI  - Imaging of musculoskeletal and spinal tuberculosis.
AB  - The diagnosis of tuberculosis of the musculoskeletal system is difficult for many
      reasons. As Walker states, to diagnose tuberculosis one must consider the
      possibility. The uncommonness of osteoarticular MTb results in clinician
      inexperience, which leads to overlooking the diagnosis. Subtle early
      manifestations may elude detection. Negative skin tests and normal chest films do
      not exclude the consideration of tuberculosis. The most conclusive means of
      reaching the diagnosis (biopsy and culture) necessitate invasive procedures that
      are not always definitive, and may require repeated attempts. Management and
      surgical decisions, however, rely on prompt diagnosis; diagnostic delay has
      prognostic implications and results in significant morbidity. Musculoskeletal
      tuberculosis produces no pathognomonic imaging signs, and in advanced stages
      mimics other disease processes. Despite these difficulties, the diagnostician's
      goal is to catch the disease as early as possible, because antibiotic treatment
      can lead to resolution and obviate more radical management. The radiologist must
      be aware of the groups at greatest risk, and typical and atypical presentations
      at imaging. The eventual eradication of MTb is conceivable, although not
      presently within our grasp. Maintaining reasonable suspicion and developing
      cognizance of the patterns of presentation allow the radiologist to diagnose
      efficiently the patient who presents with osteoarticular tuberculosis.

PMID- 11316363
TI  - Imaging of musculoskeletal and spinal infections in AIDS.
AB  - The diagnosis of common and opportunistic infections in patients with HIV begins
      with clinical suspicion and involves relatively standard methodology.
      Musculoskeletal infection is sometimes the first manifestation of an HIV
      infection. In patients with HIV, the infections tend to be more advanced at
      presentation, occur in unusual sites, are caused by a wider spectrum of
      pathogens, and tend to show an inadequate or delayed response to therapy. The
      index of suspicion for musculoskeletal infections should be high when reviewing
      imaging studies of patients with HIV.

PMID- 11316364
TI  - Imaging of fungal, viral, and parasitic musculoskeletal and spinal diseases.
AB  - There are many nonbacterial infections that have musculoskeletal manifestations
      and radiologic findings. These infections produce a limited range of tissue
      responses, depending on the organism, the tissue compartment affected, and the
      immune competence of the host. Diagnosis is dependent on obtaining an appropriate
      travel or geographic history, the clinical and laboratory features, and on
      occasion the specific radiologic findings.

PMID- 11316365
TI  - Genetic interference in protozoa.
AB  - RNA interference first described in Caenorhabditis elegans and transgene-induced
      post-transcriptional gene silencing first described in plants and fungi now
      appear as different means of activating a conserved and ancient mechanism that
      can protect genomes against viruses and transposons and perhaps also control
      expression of endogenous genes. We present here similar genetic interference
      phenomena in highly divergent protozoa, Trypanosoma and Paramecium, and look
      ahead to what contribution these microorganisms could bring to this fast-moving
      area.

PMID- 11316366
TI  - Distinctive features of homologous recombination in an 'old' microorganism,
      Lactococcus lactis.
AB  - Homologous recombination is needed to assure faithful inheritance of DNA
      material, especially under stress conditions. The same enzymes that repair broken
      chromosomes via recombination also generate biodiversity. Their activities may
      result in intrachromosomal rearrangements, assimilation of foreign DNA, or a
      combination of these events. It is generally supposed that homologous
      recombination systems are conserved, and function the same way everywhere as they
      do in Escherichia coli, the accepted paradigm. Studies in an 'older'
      microorganism, the gram-positive bacterium of the low GC branch Lactococcus
      lactis, confirm that many enzymes are conserved across species lines. However,
      the main components of the double strand break (DSB) repair system, an
      exonuclease/helicase (Exo/hel) and a short DNA modulator sequence Chi, differ
      markedly between bacteria, especially when compared to the gram-negative
      analogues. Based on our studies, a model is proposed for the functioning of the
      two-subunit Exo/hel of L. lactis and other gram-positive bacteria, which differs
      from that of the three-subunit E. coli enzyme. The differences between bacterial
      DSB repair systems may underlie a selection for diversity when dealing with DSB.
      These and other features of homologous recombination in L. lactis are discussed.

PMID- 11316367
TI  - Variant antigens of Plasmodium falciparum encoded by the var multigenic family
      are multifunctional macromolecules.
AB  - Cytoadhesion of parasitized red blood cells (PRBCs) to vascular endothelial cells
      (sequestration) and binding of unparasitized RBCs to PRBCs (rosetting) are
      virulence factors of Plasmodium falciparum, the species responsible for lethal
      human malaria. Variant antigens involved in both phenomena have been identified
      as products of the multicopy var gene family. In this review, progress in the
      understanding of molecular mechanisms of sequestration is summarized, in
      particular, concerning the structure of var gene products related to specificity
      of binding to endothelial receptors, and the origin of var gene diversity.

PMID- 11316368
TI  - Distinct levels of genetic diversity of Borrelia burgdorferi are associated with
      different aspects of pathogenicity.
AB  - Different species of pathogenic Borrelia show different symptoms and tick vector
      specificity. Even within regions where only one species is found, Lyme disease
      progresses very differently from one patient to another. Since Borrelia shows
      very little recombination either within or between species, alleles of a gene can
      be used to mark clones. The ospC gene is highly variable within each species and
      can be used to define groups of related clones. It has been previously shown that
      only four out of seventeen ospC groups of Borrelia burgdorferi sensu stricto
      cause invasive forms of the disease. Other groups cause erythema migrans, a skin
      rash at the site of the tick bite, but not invasive disease, while still other
      groups seem to be nonpathogenic to humans. In this study we extend the analysis
      of the ospC gene to the other pathogenic species, Borrelia garinii and Borrelia
      afzelii. Only two groups in B. afzelii and four groups in B. garinii cause
      invasive disease. Thus, only ten out of the 58 defined ospC groups cause invasive
      and presumably chronic Lyme disease.

PMID- 11316369
TI  - Identification of salivary Lactobacillus rhamnosus species by DNA profiling and a
      specific probe.
AB  - The Lactobacillus genus has been shown to be associated with the dental carious
      process, but little is known about the species related to the decay, although
      Lactobacillus rhamnosus is suspected to be the most implicated species.
      Conventional identification methods based on biochemical criteria lead to
      ambiguous results, since the Lactobacillus species found in saliva are
      phenotypically close. To clarify the role of this genus in the evolution of
      carious disease, this work aimed to find a rapid and reliable method for
      identifying the L. rhamnosus species. Methods based on hybridization with DNA
      probes and DNA amplification by PCR were used. The dominant salivary
      Lactobacillus species (reference strains from the ATCC) were selected for this
      purpose as well as some wild strains isolated from children's saliva. DNA
      profiling using semirandom polymorphic DNA amplification (semi-RAPD) generated
      specific patterns for L. rhamnosus ATCC 7469. The profiles of all L. rhamnosus
      strains tested were similar and could be grouped; these strains shared four
      common fragments. Wild strains first identified with classic methods shared
      common patterns with the L. rhamnosus species and could be reclassified. One
      fragment of the profile was purified, cloned, used as a probe and found to be
      specific to the L. rhamnosus species. These results may help to localize this
      species within its ecological niche and to elucidate the progression of the
      carious process.

PMID- 11316370
TI  - Probiotic activities of Lactobacillus casei rhamnosus: in vitro adherence to
      intestinal cells and antimicrobial properties.
AB  - The interest of probiotics as remedies for a broad number of gastrointestinal and
      other infectious diseases has gained wide interest over the last few years, but
      little is known about their underlying mechanism of action. In this study, the
      probiotic activities of a human isolate of Lactobacillus casei subsp. rhamnosus
      strain (Lcr35) were investigated. Using intestinal Caco-2 cell line in an in
      vitro model, we demonstrated that this strain exhibited adhesive properties. The
      inhibitory effects of Lcr35 organisms on the adherence of three pathogens,
      enteropathogenic Escherichia coli (EPEC), enterotoxigenic E. coli (ETEC) and
      Klebsiella pneumoniae, were determined. A decrease in the number of adhering
      pathogens was observed, using either preincubation, postincubation or
      coincubation of the pathogens with Lcr35. Moreover, the antibacterial activities
      of cell-free Lcr35 supernatant was examined against nine human pathogenic
      bacteria, ETEC, EPEC, K. pneumoniae, Shigella flexneri, Salmonella typhimurium,
      Enterobacter cloacae, Pseudomonas aeruginosa, Enterococcus faecalis and
      Clostridium difficile. The growth of all strains was inhibited, as measured by
      determining the number of viable bacteria over time, but no bactericidal activity
      was detected in this in vitro assay. Together, these findings suggest that this
      probiotic strain could be used to prevent colonization of the gastrointestinal
      tract by a large variety of pathogens.

PMID- 11316371
TI  - Characterisation of a Listeria monocytogenes mutant deficient in D-arabitol
      fermentation.
AB  - We selected and analysed a Tn917-lac Listeria monocytogenes mutant deficient in D
      arabitol fermentation. Comparison of the 310-aa-long translated partial sequence
      of the disrupted gene with known proteins showed similarity with the
      phosphotransferase system galactitol-specific enzyme IIC component of the
      alkaliphilic Bacillus halodurans (50% identity) and of Escherichia coli (36%
      identity). Fermentation of 18 other carbohydrates was unimpaired, suggesting the
      specificity of this transmembrane permease IIC for the pentitol D-arabitol. The
      deficiency in D-arabitol fermentation did not alter L. monocytogenes virulence in
      the BALB/c mouse model after intravenous and intragastric inoculations. This
      fully virulent mutant is a valuable tool to study L. monocytogenes oral
      infection, since the antibiotic resistance marker present on the Tn917-lac
      transposon will efficiently select L. monocytogenes against the intestinal
      microflora.

PMID- 11316372
TI  - Qualitative and quantitative molecular detection of enteroviruses in water from
      bathing areas and from a sewage treatment plant.
AB  - Pathogenic enteric viruses can be introduced into the environment as a result of
      human activities. Enteroviruses are regularly detected in environmental waters or
      shellfish and can provoke potentially serious diseases. Some authors believe that
      enteroviruses could represent an interesting indicator of viral contamination in
      the environment. Since molecular approaches seem to be promising for the
      detection of these viruses, we developed a simple qualitative RT-PCR procedure
      for enteroviruses, together with a quantitative RT-PCR assay using RNA internal
      standard. After one-tube-RT-PCR, this standard and wild enterovirus RNA were
      detected by differential hybridization with specific probes and a fluorimetric
      reaction. The quantification of enteroviruses, conducted in a sewage treatment
      plant, showed a decreasing number of genomic copies from the entrance to the exit
      (from 3.8 x 10(5) to 5.4 x 10(4) RNA copies/mL) but indicated the presence of
      enterovirus RNA in the neighboring river (2.2 x 10(3) RNA copies/mL). In bathing
      areas, enterovirus RNA was detected in 16 out of 226 samples, with copies numbers
      ranging from 3.7 x 10(2) RNA copies/mL to 7 x 10(4) RNA copies/mL.

PMID- 11316373
TI  - Improving the display of proteins on filamentous phage.
AB  - In phage display technology, polypeptides are displayed on the surface of
      filamentous bacteriophage by genetic fusion to a coat protein. However, the
      fraction of phage particles bearing the fusion protein can be low. Here we found
      that we could improve the display of a protein (Stoffel fragment of Taq
      polymerase fused to the p3 protein of the phage) by mutation of the signal
      sequence and use of helper phage with a protease-cleavable coat protein. Over
      multiple rounds of infection, proteolysis and binding to an anti-Taq antibody, we
      were able to select strongly for display of the fusion protein (> 50-fold), and
      for mutations in the translation initiation region and in the signal sequence of
      the fusion. This suggests a general means of improving the display of proteins on
      phage.

PMID- 11316374
TI  - DWI prevention: profiles of drinkers who use designated drivers.
AB  - The effectiveness of designated driver (DD) use in preventing driving while
      intoxicated (DWI) depends on whether drinkers at risk for DWI use DDs. Bivariate
      and logistic regression analyses conducted on data from 1,391 Computer-Assisted
      Telephone Interviews (CATIs) and from 902 barroom patron surveys showed that DD
      users, compared to nonusers, tended to be at-risk, heavier drinkers. For example,
      logistic regression using the CATI sample indicated that DD users were more
      likely to drink more often outside the home, to achieve higher blood alcohol
      concentrations (BACs) when drinking outside the home, to ride with intoxicated
      drivers (RID), and to be heavy drinkers on D. Cahalan et al.'s (1969) Quantity
      Frequency-Variability (QFV) index. Similarly, logistic regression using the
      barroom sample showed that DD users tended to be heavy drinkers on the QFV index,
      and were more likely to drive after drinking and to ride with intoxicated
      drivers. Additional analyses showed that DD users also were more likely than
      nonusers to engage in other behavior to avoid DWI, such as drinking less, waiting
      to drive until the effects of alcohol diminish, walking home, and staying
      overnight. These results are consistent with other findings from a related study
      by the current authors which showed that at-risk drinkers also used free safe
      (taxi) rides to avoid DWI, however were still more likely to report DWI and RID
      behavior (B. D. Caudill, W. M. Harding, & B. Moore, in press). Consequently, DWI
      prevention efforts may be improved by future research aimed at learning why such
      at-risk drinkers sometimes take steps to avoid DWI and sometimes do not.

PMID- 11316375
TI  - Naltrexone and relapse prevention treatment for cocaine-dependent patients.
AB  - A double-blind, placebo-controlled clinical trial examining the joint action of
      naltrexone (NTX) in combination with relapse prevention (RP) therapy for the
      treatment of cocaine dependence was conducted. Eighty-five participants who
      achieved initial abstinence during the intake evaluation and detoxification phase
      of the study were randomized into 1 of 4 combined NTX (0 vs. 50 mg) by therapy
      (RP vs. Drug Counseling) experimental conditions for the 12-week outpatient
      treatment phase of the study. A random effects regression model to test for group
      differences on percentage of cocaine-positive urines indicated a significant time
      by medication by therapy interaction, suggesting less cocaine use over time among
      subjects receiving RP-50 mg than those in the other conditions. No differences
      were found for retention or time until first cocaine-positive urine. Naltrexone
      was well tolerated by participants, with acceptable rates of medication
      compliance observed. Treatment integrity measures confirmed successful
      manipulation of the psychotherapy. These results are consistent with the notion
      that substance use in dependent patients can be reduced with a combination of
      coping skills training and pharmacologic treatments.

PMID- 11316376
TI  - Social network drinking and adult alcohol involvement: a longitudinal exploration
      of the direction of influence.
AB  - Past research shows consistent associations between individuals' drinking
      patterns and the drinking patterns of their social network members. This
      association has usually been attributed to the influence of social networks on
      individual behavior. Recent studies concerning adolescent drinking behavior
      suggest that such associations may be due, in part, to selection effects in which
      individuals form social ties with those who have drinking habits similar to their
      own. The present study used longitudinal data and structural equation modeling to
      compare the selection and influence effects among a large representative sample
      of adults. Results suggested that both selection and influence affect the
      association between individual and network drinking patterns among adults, but
      that social selection effects are substantially stronger than social influence
      effects. A cross-lagged structural equation model with a normed fit index of
      .975, showed that the path indicating peer influence had a coefficient of .069
      (P<.01), whereas the path indicating network selection had a coefficient of .193
      (P<.01). Comparisons across age, race, sex, and marital status groups revealed
      similar results, with stronger selection than influence effects for all groups.

PMID- 11316377
TI  - Smoking in adolescence do attitudes matter?
AB  - A number of factors have emerged as being associated with adolescent smoking.
      While theoretical evidence suggests that attitude can be an important factor
      influencing smoking, empirical findings are somewhat contradictory. The main goal
      of the present study has been to identify the characteristics/dimensions of
      attitudes toward smoking in adolescence. Data were collected among primary
      (Grades 7-8), and secondary (Grades 9-12) school students using randomly selected
      classes in Szolnok, Hungary (N= 261). The self-administered questionnaire
      consisted of questions on sociodemographics, smoking behavior, beliefs, and
      attitudes related to smoking (items adapted from The Students' Health and
      Lifestyle Study developed by the research team of The University of Western
      Ontario, Canada). Factor analysis of the statements concerning smoking gave five
      factors: antismoking attitude, liking attitude, worrying attitude, disliking
      attitude, and unrealistic attitude. Antismoking attitude proved to be the most
      important influencing factor of tobacco use, which was greatly independent from
      the number of smoking friends in boys and older adolescents. However, peer
      smoking could definitely moderate this attitude and thus the linkage between
      attitude and smoking activity in girls and younger adolescents. Our findings
      support the idea that antismoking interventions can be adapted to the target
      groups as programs may have different impact on boys and girls and on different
      age groups.

PMID- 11316378
TI  - Psychometric evaluation of the marijuana and stimulant effect expectancy
      questionnaires for adolescents.
AB  - Alcohol expectancies are important in the mediation and prediction of alcohol
      use. Expectancies for the effects of other drugs, although less well delineated,
      appear equally important. Therefore, development and validation of expectancy
      measures for drugs other than alcohol is necessary for evaluating the importance
      of these constructs. We examined the factor structure, reliability, and validity
      of the Marijuana Effect Expectancy Questionnaire (MEEQ) and the Stimulant Effect
      Expectancy Questionnaire (SEEQ) in clinical and community samples of adolescents
      as they moved into young adulthood (N=279). Confirmatory factor analyses (CFAs)
      supported the a priori factors, and we found good reliability for most individual
      scales. Temporal stability and convergent and discriminant validity of drug
      effect expectancies were supported in this sample of adolescents and young
      adults. Drug effect expectancies were associated with drug preference and drug
      use patterns over 2 years. Use of these measures may aid our understanding of the
      etiology and course of marijuana and stimulant involvement during adolescence and
      young adulthood.

PMID- 11316379
TI  - Subtypes within the precontemplation stage of adolescent smoking acquisition.
AB  - The present study examined the existence of three possible subtypes within the
      precontemplation stage of smoking acquisition: committers, immotives, and
      progressives. The sample of the study included young people from six European
      countries (mean age = 13 years) who had never smoked regularly (n = 21 535). A
      cross-sectional design was used to assess cognitive determinants of smoking
      behavior: attitudes towards smoking, perceived social influences, and self
      efficacy to remain a nonsmoker. Adolescents within the various stages of smoking
      acquisition were compared with regard to standardized T scores on these risk
      factors. The results showed that adolescents in the three subgroups of
      precontemplation differed from each other on every cognitive determinant tested,
      revealing a higher risk to start smoking among progressives than among immotives.
      Immotives revealed a higher risk to start smoking than committers. It is
      concluded that the use of subtypes within acquisition precontemplation in
      research on adolescent smoking may be a promising tool for investigating the
      initiation continuum and for improving the quality of both the implementation and
      evaluation of prevention programs.

PMID- 11316380
TI  - Restrictive dieting vs. "undieting" effects on eating regulation in obese clinic
      attenders.
AB  - This study tested predictions from restraint theory [Herman & Polivy (1984). A
      boundary model for the regulation of eating. In: A. J. Stunkard, & E. Stellar
      (Eds.), Eating and its disorders (pp. 141-156) New York: Raven Press.] and the
      three-factor model of dieting [Psychol. Bull. 114 (1993) 100.] using an eating
      regulation paradigm. Participants were 42 obese, nonbinge eaters assigned to
      either a weight loss group (restrictive dieters or RDs) or a group designed to
      eliminate dieting ("undieters" or UDs). Participants took part in an ostensible
      ice cream taste test with or without a preload, both before and after the weight
      control intervention. At pretest, restraint theory's prediction that participants
      would engage in counter-regulatory eating was not supported. At posttest, after 8
      weeks of the dieting interventions, RDs increased and UDs decreased their intake
      following a preload, a pattern most consistent with the predictions of restraint
      theory. This counter-regulatory trend was observed in spite of a significant
      decrease in RDs' Disinhibition scale scores following treatment. Implications of
      these findings for restraint theory, the three-factor model of dieting, and
      relapse in obesity treatment were discussed.

PMID- 11316381
TI  - Motivating drinking behavior change depressive symptoms may not be noxious.
AB  - Depression often hinders behavior change among people who abuse alcohol; it
      adversely affects self-efficacy and is associated with poor outcomes. However,
      the Transtheoretical Stages of Change Model suggests that personal discomfort,
      namely if the costs of drinking outweigh the benefits, may lead to behavior
      change. Often such alcohol-related consequences are associated with depression.
      Seventy-five alcohol-abusing participants, ages 18-50, completed the Beck
      Depression Inventory (BDI), Losses Of Significance Self-report Questionnaire
      Revised (LOSS-QR), Situational Confidence Questionnaire-42 (SCQ-42), the Brief
      Readiness to Change Questionnaire (RTC), and the Steady Pattern Chart (SP) at
      baseline and again 3 months later. BDI scores were significantly associated with
      all three RTC stage scores. LOSS-QR scores significantly predicted BDI scores but
      SCQ-42 scores did not. Interestingly, BDI scores did not predict changes in
      drinking rates over time. Greater levels of depressive symptoms, perhaps
      associated with awareness of negative drinking consequences, may promote rather
      than hinder motivation to change drinking behavior among people.

PMID- 11316382
TI  - Clinical correlates of heavy tobacco use among adolescents.
AB  - The primary aim of this study was to determine the clinical factors
      differentiating adolescents with heavy smoking (> or = 10 cigarettes/day) from
      adolescents with light smoking. This study involved a study group of 812
      adolescents recruited from adolescent alcoholism treatment centers and from the
      community. Logistic regression analyses demonstrated that adolescents with heavy
      smoking, compared with adolescents with light smoking, were significantly more
      likely to demonstrate Caucasian American ethnicity, drug-use disorders, alcohol
      use disorders, and conduct disorder. Our findings suggest that the clinical
      correlates of heavy smoking among adolescents are generally similar to those for
      smoking at any level (vs. nonsmokers), except that heavy smoking is more strongly
      associated with Caucasian American ethnicity. Also, depressive disorders were
      associated with smoking at any level in our sample, but depressive disorders were
      not associated with heavy smoking.

PMID- 11316384
TI  - Comparison of drug treatment histories of single and multiple drug abusers in
      detox.
AB  - This study was undertaken to determine differences in previous treatment patterns
      in individuals currently using different numbers of substances. Medical records
      of 1198 inpatient detoxification (detox) admissions were analyzed. Numbers of
      past admissions to completed detox, methadone, or other types of drug abuse
      treatment were totaled and ranked to determine most frequent type. Within gender,
      treatment histories of single and multiple drug abusers usually do not differ.
      The one exception is male multiple drug abusers ages 26-30, who show increased
      admissions. Possible explanations are that men do not seek treatment before
      developing medical complications of addiction or until external factors influence
      admission. There were differences in treatment histories between genders in
      multiple drug abusers only. Before age 30, women reported increased treatment of
      certain types. Possible explanations are that treatment priority is given to
      women who are, or may be, pregnant. Also, younger men may not enter or complete
      treatment. Previous treatment history may influence many behaviors. The results
      of this study delineate several valuable indicators for assessing past history.

PMID- 11316383
TI  - The association of testosterone with nicotine use in young adult females.
AB  - This pilot laboratory study examined the relationship of testosterone levels,
      carbon monoxide (CO) levels, current and adolescent nicotine use, and histories
      of pubertal onset in 30 young adult female smokers. These females had completed
      questionnaires regarding nicotine use in the 7th through 10th grades, and again
      at age 21 as part of a cohort study of drug use. In addition, history of pubertal
      onset was obtained at age 21, as were testosterone and CO levels. Testosterone
      levels were positively correlated with cigarette use in the last 30 days (P< or
      =.01), CO levels (P< or =.05), cigarette use reported in the 7th and 10th grades
      (P< or =.05), and negatively correlated with age of pubertal onset (P< or =.001).
      The relationship of testosterone to nicotine will be discussed.

PMID- 11316385
TI  - Multimodal assessment of the effect of chewing gum on nicotine withdrawal.
AB  - The present study was designed to evaluate the usefulness of chewing gum to
      reduce nicotine withdrawal, craving, and salivary cortisol concentrations during
      temporary nicotine deprivation. A total of 20 male smokers were studied under
      conditions when gum was and was not accessible during a 4-hour deprivation
      period. All subjects smoked an initial cigarette shortly after arrival for the
      two experimental sessions and were informed that they would be unable to smoke
      for the remainder of each session. The sessions consisted of each subject
      watching a movie, then waiting in the lab for two consecutive 30-min intervals.
      Self-reported nicotine withdrawal and craving were assessed four times and
      salivary cortisol five times during each experimental session. Results from this
      study indicate that chewing gum helps with self-reported withdrawal but not
      craving when a smoker is prevented from smoking. This study also provides
      preliminary data on the use of salivary cortisol as a physiological marker that
      may map these self-reports of nicotine withdrawal and craving.

PMID- 11316386
TI  - Environmental influences, employment status, and religious activity predict
      current cigarette smoking in the elderly.
AB  - The objective of this study was to describe the smoking histories, patterns of
      cigarette use, and quitting behaviors in a predominantly African American sample
      of older adults. Study participants were a convenience sample of senior center
      attendees in the Washington, DC metropolitan area. Self-report questionnaires
      were used to measure depression, nicotine dependence, smoking motives, and
      readiness to quit. Results showed that living with another smoker increased the
      likelihood of current smoking (odds ratio = 2.07, 95% CI = 1.72-36.73). Being
      employed or seeking work was also associated with a higher likelihood of current
      smoking (odds ratio = 2.73, 95% CI = 2.00-118.76). Subjects who reported less
      frequent participation in organized religious activities were also more likely to
      smoke (odds ratio = 2.04, 95% CI = 1.17-50.38). Both former and current smokers
      identified personal will power and physician advice as the two most influential
      factors in successful smoking cessation. However, current smokers believed that
      nicotine replacement would aid in a successful cessation attempt, while former
      smokers did not endorse the efficacy of these products. The findings are
      discussed in terms of implications for intervention.

PMID- 11316387
TI  - A factor analysis of the fagerstrom tolerance questionnaire.
AB  - A factor analysis of 1309 Fagerstrom Tolerance Questionnaires (FTQ) was performed
      with LISCOMP software, which utilizes tetrachoric correlations to account for the
      dichotomous responses of the FTQ. Three factors with eigenvalues greater than 1.0
      were obtained, accounting for 56.6% of the variance. Factor 1 was loaded by
      questions "How soon on waking do you smoke your first cigarette?," "Do you find
      it difficult to refrain from smoking in places it is forbidden?," "How many
      cigarettes a day do you smoke?," and "Do you smoke if you are so ill that you are
      in bed most of the day?" Factor 2 was loaded by questions "Which cigarette would
      you hate to give up?" and "Do you smoke more during the morning than during the
      rest of the day?" Factor 3 was loaded exclusively by question "What brand do you
      smoke?" The question "Do you inhale always, sometimes, or never?" loaded
      exclusively on a fourth factor, however its eigenvalue did not reach
      significance. Support is provided for the modification of the eight-item FTQ to
      the six-item Fagerstrom Test for Nicotine Dependence (FTND). Based on the wording
      of the questions that loaded on each factor, we propose that Factor 2 assesses
      the degree of urgency to initiate smoking after overnight abstinence and that
      Factor 1 reflects the persistence of smoking during waking hours.

PMID- 11316388
TI  - Religion and fertility among the Atyap in Nigeria.
AB  - Using data obtained in 1995 from 600 Atyap women in randomly selected dwellings
      in Kaduna State, Nigeria, multiple regression analysis shows that Catholics and
      Other Protestants (Anglicans and Baptists) have higher fertility than women
      affiliated to the Evangelical Churches of West Africa (ECWA), even net of
      compositional characteristics of the two groups. Above and beyond the
      denominational differences, the regression analysis also shows that the stronger
      the religious belief, the higher the fertility. Thus, the study underscores the
      need for researchers of the religion-fertility association in Nigeria to examine
      the influence of religious denomination and religiosity on fertility, within each
      of the main religions.

PMID- 11316389
TI  - Evidence of diffusion from a targeted HIV/AIDS intervention in the Dominican
      Republic.
AB  - The diffusion potential of a targeted HIV/AIDS intervention that enlisted peer
      educators to disseminate 'safer sex' messages and condoms among female commercial
      sex workers and their clients was evaluated in the Dominican Republic. Levels of
      interurban interaction potential were ascertained that linked the targeted city
      of La Romana with the proximate cities of San Pedro de Macoris and Guaymate.
      Weekly service statistics generated over an 8-month period were analysed to
      establish activity areas for the peer educators. Data were entered and analysed
      using a geographic information system and interurban linkages were established.
      Project outcomes were examined via a series of three cross-sectional Knowledge,
      Attitudes and Practices (KAP) surveys conducted among convenience samples of
      commercial sex workers at the start of the intervention and at 4 and 8 months.
      The results attest to a high degree of interconnectivity between the targeted and
      proximate cities, and a pattern of interurban mobility that links commercial sex
      workers, clients and establishments in all three cities. The examination of
      project outcomes revealed statistically significant changes in condom use in the
      targeted city of La Romana among commercial sex workers, as well as among their
      counterparts interviewed in the proximate cities of San Pedro de Macoris and
      Guaymate. These data suggest a diffusion effect. It is concluded that a targeted
      intervention may influence proximate cities within a relatively compressed period
      of time. The findings suggest the importance of considering geographic diffusion
      principles, such as urban hierarchies, regional nodes and transportation
      linkages, when designing HIV/AIDS prevention efforts. It also has important
      implications in the selection of control sites when conducting experimental
      studies of HIV/AIDS interventions.

PMID- 11316390
TI  - Consistency in condom use in the context of HIV/AIDS in Zimbabwe.
AB  - Against the backdrop of a high prevalence of the human immunodeficiency virus
      infection in Zimbabwe, this paper analyses data from the 1997 Zimbabwe Sexual
      Behaviour and Condom Use Survey to throw light on the degree to which sexually
      active adults consistently use condoms in high-risk sexual situations. The
      multivariate results indicate that at the time of the survey, consistent condom
      use in non-marital relationships is significantly higher for males than females,
      higher among those who had access to information about condoms from multiple
      sources than among those with limited access, and higher among those who have
      positive attitudes to condoms than among those with negative attitudes. Even
      though consistent condom use with non-marital partners is higher for those who
      know a source where condoms can be obtained, this effect is due to the fact that
      these respondents have more positive attitudes towards condoms. Likewise, the
      higher levels of consistent condom use exhibited by those who are aware of the
      efficacy of condoms are due to the fact that men have higher awareness of this,
      and men use condoms more consistently than women. In sum, the results suggest
      that the effects of the respondents' sex and their knowledge of the prophylactic
      importance of condoms and where condoms might be obtained are a function of other
      socioeconomic advantages they have. It is, therefore, concluded that programmes
      that use mass media information, education and communication campaigns to reduce
      shyness, embarrassment and stigma about condom use can help increase consistent
      use of condoms in non-marital relationships in Zimbabwe.

PMID- 11316391
TI  - Gender relations: husband-wife fertility and family planning decisions in Kenya.
AB  - Although Kenya's fertility rate has declined from 6.7 births per woman in the mid
      1980s to 5.4 births per woman in 1993 (NCPD, 1994), population growth is still
      high, yielding a doubling time of 35 years. This study uses the 1993 Kenya
      Demographic Health Survey data collected from 1257 couples to examine the
      socioeconomic and sociodemographic characteristics of married men and women and
      their communication with their spouses over fertility and family planning
      decision-making practices. The logistic regression analysis shows that education
      for both men and women, discussion of fertility and family planning between
      spouses, male approval of use of contraception and male family size desires are
      important factors that influence ever-use of family planning.

PMID- 11316392
TI  - Colostrum feeding behaviour and initiation of breast-feeding in rural Bangladesh.
AB  - Human breast milk is primarily colostrum immediately following birth. Colostrum
      gradually changes to mature milk over the next several days. The role of
      colostrum in fighting infections and promoting growth and development of the
      newborn is widely acknowledged. This role is mediated by differences across
      cultures in the acceptability of colostrum and the prevalence of colostrum
      feeding. This study examined the prevalence of colostrum feeding and time to
      initiation of breast-feeding in 143 rural Bangladeshi women in Matlab thana.
      Structured interviews were collected during a 9-month prospective study conducted
      in 1993. Women were usually interviewed within 4 days of giving birth and were
      asked about whether or not they fed their child colostrum and the number of hours
      until they began breast-feeding the baby. Ninety per cent of the mothers reported
      feeding their newborn colostrum. A logistic regression found no effect on the
      prevalence of colostrum feeding from the following covariates: mother's age,
      parity, history of pregnancy loss, child's sex, mother's self-report of delivery
      complications, and the time from birth to interview. Fifty-nine per cent of
      mothers initiated breast-feeding within 4 h, and 88% within 12 h of parturition.
      Survival analysis was used to estimate the effects of covariates on the time from
      delivery to initial breast-feeding. Time to initial breast-feeding was delayed
      slightly, but significantly, for older mothers, for male infants, and by mothers
      who did not report delivery complications. The percentage of mothers who fed
      their child colostrum was higher, and times to initial breast-feeding were
      shorter, than almost all previous reports from South Asia. These findings might
      be explained, in part, by methodological differences among studies, but it is
      suggested that recent changes towards earlier initiation of breast-feeding have
      taken place in rural Bangladesh.

PMID- 11316393
TI  - The ethnic minorities of southern Italy and Sicily: relationships through
      surnames.
AB  - Surnames of grandparents were collected from children in the primary schools of
      the Albanian-Italian, Croat-Italian and Greek-Italian villages of southern Italy
      and Sicily. The coefficients of relationships by isonymy show almost no
      relationship with ethnicity. Ethnolinguistic minorities of southern Italy and
      Sicily are geographically subdivided into two main clusters: the first cluster
      comprises the Albanian, Croat and Greek communities of the Adriatic area; and the
      second cluster comprises the Albanian and Greek communities of the Ionian,
      Thirrenian and Sicilian areas.

PMID- 11316394
TI  - Covariates of child mortality in Mali: does the health-seeking behaviour of the
      mother matter?
AB  - This paper uses data from the 1995/96 Mali DHS survey to examine the importance
      of a wide range of socioeconomic, behavioural and biodemographic factors in the
      determination of child mortality in Mali, with a special focus on maternal
      education and behaviour. The central hypothesis of the study is that advances in
      maternal education would contribute little to child survival in settings such as
      Mali's urban and rural communities where progress in educational attainment is
      not matched with improvements in other aspects of socioeconomic development such
      as economic growth, job creation, financial security and public health and
      medical resources. Units of analysis are children born in the past 5 years to DHS
      respondents (women aged 15-45) who were married at the time of the survey. The
      Cox proportional hazards regression technique has been used to estimate the net
      effects of variables included as covariates. The findings indicate that the
      health-seeking behaviour of the mother matters more than maternal education in
      explaining the observed differences in infant and child mortality in Mali's urban
      and rural areas.

PMID- 11316395
TI  - Estimates of cousin marriage and mean inbreeding in the United Kingdom from
      'birth briefs'.
AB  - From 626 ascendant genealogies, known as 'birth briefs', deposited by members of
      the Society of Genealogists in their London library, rates of consanguineous
      marriage and coefficients of mean inbreeding (a) of offspring were estimated for
      cohorts of marriages contracted in the late nineteenth and early twentieth
      centuries. The rate of first cousin marriage in the generation estimated to have
      married during the 1920s was 0.32%, with no marriages between second cousins. The
      mean inbreeding coefficient for the offspring of these marriages was estimated as
      0.0002. In the previous generation 1.12% of the marriages were between first
      cousins, and the estimate of mean inbreeding was 0.0007. Comparison with data
      taken from the published literature suggests that the levels of cousin marriage
      observed are consistent with a secular decline during the late nineteenth and
      twentieth centuries.

PMID- 11316396
TI  - Aboriginal mortality in Canada, the United States and New Zealand.
AB  - Indigenous populations in New World nations share the common experience of
      culture contact with outsiders and a prolonged history of prejudice and
      discrimination. This historical reality continues to have profound effects on
      their well-being, as demonstrated by their relative disadvantages in
      socioeconomic status on the one hand, and in their delayed demographic and
      epidemiological transitions on the other. In this study one aspect of
      aboriginals' epidemiological situation is examined: their mortality experience
      between the early 1980s and early 1990s. The groups studied are the Canadian
      Indians, the American Indians and the New Zealand Maori (data for Australian
      Aboriginals could not be obtained). Cause-specific death rates of these three
      minority groups are compared with those of their respective non-indigenous
      populations using multivariate log-linear competing risks models. The empirical
      results are consistent with the proposition that the contemporary mortality
      conditions of these three minorities reflect, in varying degrees, problems
      associated with poverty, marginalization and social disorganization. Of the three
      minority groups, the Canadian Indians appear to suffer more from these types of
      conditions, and the Maori the least.

PMID- 11316397
TI  - Neonatal mortality and maternal health care in Nepal: searching for patterns of
      association.
AB  - This study explores the factors associated with neonatal mortality and maternal
      health care in Nepal. The subjects were 4375 births reported in the 1996 Nepal
      Family Health Survey. Maternal and child health care was found to have a
      significant association with neonatal mortality, although preceding birth
      interval and sex of child had stronger effects. Four aspects of maternal care
      were found to be highly associated with region, household ownership of assets,
      mother's education and father's education. This indicates that accessibility,
      affordability and availability of maternal health care are important factors to
      consider in future research on neonatal mortality.

PMID- 11316398
TI  - Use of venous thromboembolism prophylaxis for surgical patients: a multicentre
      analysis of practice in Spain.
AB  - OBJECTIVE: To assess the use of venous thromboembolism prophylaxis in surgical
      patients. DESIGN: Retrospective multicentre study. SETTING: Eight acute-care
      teaching hospitals with more than 400 beds, Spain. PATIENTS: Medical records of
      all consecutive patients undergoing operations in the general surgical and trauma
      and orthopaedic services during the month of April, 1997, were randomly selected.
      INTERVENTION: The sample size for each type of operation (general, trauma
      orthopaedic) was calculated from the number of operations done at each hospital
      (with an absolute precision of 5%, and an alpha error of 5%) and the prevalence
      of the use of venous thromboembolism prophylaxis obtained from a random sample of
      50 records (25 from patients in general surgery and 25 from patients in
      orthopaedic surgery) from each centre. MAIN OUTCOME MEASURES: Appropriate and
      inappropriate pharmacological prophylaxis defined according to a combination of
      risk categories for venous thromboembolism, doses of antithrombotic agents given,
      time of starting prophylaxis, and its duration. RESULTS: A total of 1848 medical
      records (general surgery, n = 1025; trauma-orthopaedic surgery, n = 823) were
      included. Physical methods (elastic stockings, intermittent pneumatic
      compression) were used in only 0.3% of patients. Pharmacological prophylaxis
      consisted of low molecular weight heparin in 99% of cases. The percentage given
      heparin-based prophylaxis was 54%. Overall, appropriate prophylaxis was given in
      1175 patients (64%). Use of thromboprophylaxis ranged from 27% to 70% among the
      participating hospitals. Prophylaxis was more likely to be appropriate in
      orthopaedic patients (577, 70%) than in general surgical patients (598, 58%) in
      both the high and moderate risk categories. CONCLUSIONS: Given the large
      variability between the participating hospitals, more specific protocols and
      recommendations about prophylaxis of thromboembolism in surgical patients are
      needed.

PMID- 11316399
TI  - Fibrinolytic activity and postoperative salvaged untreated blood for autologous
      transfusion in major orthopaedic surgery.
AB  - OBJECTIVE: To evaluate the fibrinolytic activity in a closed surgical wound, in
      postoperatively drained blood, and during autologous transfusion. DESIGN:
      Prospective study. SETTING: National hospital, Norway. PATIENTS: 9 patients
      operated on for thoracic scoliosis. MAIN OUTCOME MEASURE: Concentrations of
      plasmin/antiplasmin (PAP), alpha2-antiplasmin, and D-dimers in drained, arterial,
      and mixed venous blood before, during, and after infusion of 10 ml/kg body weight
      of postoperatively drained, untreated blood. RESULTS: In drained blood the
      concentration of alpha2-antiplasmin was 31% of the preoperative arterial control
      value. Together with the increased concentrations of PAP to 18076 microg/L and D
      dimers to 126 mg/L, this indicates extensive fibrinolytic activity in the closed
      wound. The postoperative autologous transfusion of drained, untreated blood
      increased the concentration of PAP from 507 to 2453 microg/L and of D-dimer from
      0.7 mg/L to 15.3 mg/L in systemic blood. CONCLUSION: The systemic concentration
      of fibrin(ogen) degradation products, indicated by D-dimers, after recirculation
      of drained, untreated blood might impair coagulation. The extensive activation of
      plasmin might exhaust available alpha2-antiplasmin in the wound and result in
      postoperative rebleeding.

PMID- 11316400
TI  - Long-term biochemical results after operative treatment of primary
      hyperparathyroidism associated with multiple endocrine neoplasia types I and IIa:
      is a more or less extended operation essential?
AB  - OBJECTIVE: To analyse our long term results in patients operated on for primary
      hyperparathyroidism associated with multiple endocrine neoplasia types I and IIa.
      DESIGN: Retrospective (data collection) and prospective (follow-up) analysis.
      SETTING: University hospital, Germany. SUBJECTS: 39 patients with MEN type I
      associated and 7 patients with MEN-type-IIa-associated primary
      hyperparathyroidism. INTERVENTIONS: Subtotal parathyroidectomy (n = 25 with MEN I
      and 1 with MEN IIa), total parathyroidectomy and autotransplantation (one in each
      group) and removal of only enlarged glands (13 with MEN type I and 5 with MEN
      type IIa). MAIN OUTCOME MEASUREMENTS: Recurrence rate of hyperparathyroidism and
      permanent hypocalcaemia postoperatively. RESULTS: Subtotal parathyroidectomy in
      patients with MEN type I gave a significantly lower recurrence rate than removal
      of only enlarged glands (3/25 compared with 3/13, log rank, p = 0.04). Permanent
      hypocalcaemia developed in 3/25 compared with 3/13, respectively. 2/5 patients
      with MEN type IIa developed recurrences after removal of only enlarged glands and
      the rate was higher than expected. CONCLUSIONS: A more extensive operation is
      essential for patients with MEN type I; the rate of permanent hypocalcaemia is
      not increased, but the recurrence rate is reduced. Patients with MEN type IIa
      should be treated by excision of enlarged glands alone, but this may be extended
      to subtotal parathyroidectomy in patients with severe symptoms.

PMID- 11316401
TI  - Sentinel node in breast cancer--a Swedish pilot study of 75 patients.
AB  - OBJECTIVE: To find out if the sentinel node can be detected in sufficient numbers
      of women with breast cancer to be useful as a prognostic sign, whether it
      reflects that state of the entire axilla, and whether it detects micrometastases
      that would otherwise be missed. DESIGN: Prospective study. SETTING: 3 teaching
      hospitals, Sweden. SUBJECTS: 75 patients with breast cancer who were listed to
      have axillary dissection as well as resection of their tumour. INTERVENTIONS:
      Injection of 99Tc nanocolloid 0.4 ml and patent blue dye 1 ml around the tumour
      or under the skin above the tumour, followed by preoperative lymphoscintigraphy
      and then identification of the sentinel node during operation either because it
      had turned blue or with a gamma probe. Removal of the sentinel node and complete
      axillary dissection. MAIN OUTCOME MEASURES: Identification of the sentinel node
      and presence of metastatic nodes in the axilla. RESULTS: The sentinel node was
      identified in 69/75 (92%). It correctly predicted the state of the axilla in
      66/69 (96%), and detected metastases in 24 of the 27 with invaded nodes in the
      axilla (89%). The false negative rate was 11%. In 14/27 with axillary metastases
      (52%) the sentinel node was the only involved node. In 3/24, metastases were
      detected by immunohistochemistry alone. CONCLUSION: Biopsy of the sentinel node
      predicted the presence or absence of axillary metastases with acceptable
      accuracy. However, before axillary node dissection is rejected in favour of
      sentinel node biopsy alone, large multicentre studies are needed to establish the
      true false negative rate.

PMID- 11316402
TI  - Preoperative oral granisetron for the prevention of postoperative nausea and
      vomiting after breast surgery.
AB  - OBJECTIVE: To evaluate the efficacy and safety of oral granisetron for the
      prevention of postoperative nausea and vomiting after breast surgery. DESIGN:
      Prospective, randomised, double-blind, placebo-controlled study. SETTING:
      University affiliated hospital, Japan. SUBJECTS: 100 women listed for partial or
      modified radical mastectomy with or without axillary dissection. INTERVENTIONS:
      Patients were given either placebo or granisetron in three different doses (1 mg,
      2 mg, 4 mg) orally 1 hour preoperatively (n = 25 in each group). A standard
      general anaesthetic technique and postoperative analgesia were used. MAIN OUTCOME
      MEASURES: All episodes of nausea and vomiting during the first 24 hours after
      anaesthesia. RESULTS: Complete response, defined as no nausea and vomiting and no
      need for a "rescue" antiemetic, during the first 24 hours after anaesthesia was
      recorded in 13 (52%) with placebo, 14 (56%) with granisetron 1 mg, 22 (88%) with
      2 mg, and 22 (88%) with 4 mg, respectively (p = 0.006, Fisher's exact test). No
      clinically serious adverse events were seen in any of the groups. CONCLUSION:
      Preoperative oral granisetron, in doses of more than 2 mg, is effective for the
      prevention of postoperative nausea and vomiting in women undergoing general
      anaesthesia for breast surgery.

PMID- 11316403
TI  - Human stomach has a recordable mechanical activity at a rate of about three
      cycles/minute.
AB  - OBJECTIVE: To discover whether the human stomach contracts every 20 seconds or
      not. DESIGN: Manometric study. SETTING: Teaching hospital, Belgium. SUBJECTS: 10
      healthy volunteers, and 31 patients who had had the whole stomach denervated and
      pulled up to the neck for oesophageal replacement. INTERVENTIONS: Analysis of
      selected strips of manometric tracings obtained with intraluminal perfused
      catheters. 13 patients were given erythromycin (1 g/day) by mouth. MAIN OUTCOME
      MEASURES: Estimation of the rate and frequency distribution according to
      amplitude of intraluminal pressure waves with the vertical axis of the tracings
      scaled up to reflect contractions within the gastric wall. RESULTS: Microwaves
      (<9 mmHg) that came in between conventional macrowaves (>9 mmHg) were found,
      showing that the human stomach undergoes mechanical activity (amplitude ranging
      from 0.2-310 mmHg) at the pacemaker's rate which varied from 2.43 to 3.60
      cycles/minute from one subject to another. Phase I of the interdigestive motor
      complex contained microwaves only, phase II and the fed pattern consisted of a
      mixture of microwaves and macrowaves, and phase III contained macrowaves only.
      The fasting rate of mechanical activity was lower in patients who were given
      erythromycin than in those not given erythromycin (p = 0.003) and in healthy
      volunteers (p=0.002), and it increased significantly after a meal (p < 0.0001).
      Microwaves in strips in which they were the most prominent were of higher
      amplitude in patients than in healthy volunteers (median: 3.5 compared with 2.5
      mmHg; p < 0.0001). CONCLUSIONS: The human stomach has mechanical activity at the
      rate at which the pacemaker generates electrical slow waves. The classic phases
      of the gastric motor activity seem to differ from each other by the frequency
      distribution of pressure waves according to amplitude rather than by the
      contraction rate. Weak mechanical activity is much more readily detectable after
      the stomach has been denervated and tailored for oesophageal substitution.

PMID- 11316404
TI  - Massive necrosis of the gastrointestinal tract after ingestion of hydrochloric
      acid.
AB  - OBJECTIVE: To describe our experience of dealing with patients admitted as
      emergencies after massive ingestion of hydrochloric acid, and to find out the
      most important prognostic factors. DESIGN: Retrospective review. SETTING:
      Teaching hospital, Spain. SUBJECTS: 21 patients with massive necrosis of the
      upper gastrointestinal tract after ingestion of acid who presented during the
      past 14 years (November 1984-March 1998). INTERVENTIONS: All patients were
      operated on immediately, 17 without an endoscopic examination. In all cases, the
      laparotomy showed various degrees of damage to the intra-abdominal oesophagus
      (from oedema to blackening) and gastric necrosis. Twelve patients also had
      necrosis of the entire duodenum. In the other nine, the necrosis did not affect
      more than the pylorus or duodenum. All these 12 patients were treated by a total
      oesophago-gastrectomy without thoracotomy. Of the 12 patients with total necrosis
      of the duodenum, 4 did not have resections and in 8, various massive resections
      of the necrotic structures were done. MAIN OUTCOME MEASURES: Mortality. RESULTS:
      Fourteen of the 21 patients died during the operation or in the early or late
      postoperative period. All 12 patients with total duodenal necrosis died, whereas
      only 2 patients in the other group. CONCLUSIONS: The ingestion of relatively
      small amounts of water-based solutions of hydrochloric acid of 24% or 32%
      concentration produces immediate and massive necrosis of the upper digestive
      tract, which results in high mortality. The poor prognosis might be improved by
      rapid responses to stop duodenal necrosis.

PMID- 11316405
TI  - Is lymphadenectomy needed for all submucosal gastric cancers?
AB  - OBJECTIVE: To find out if it is feasible to extend the indication for local
      resection of submucosal gastric cancer without increasing the risk of lymph node
      metastases. DESIGN: Retrospective study. SETTING: University hospital, Japan.
      SUBJECTS: 104 patients with gastric cancer confined to the submucosal layer who
      underwent conventional gastrectomy with lymphadenectomy. INTERVENTIONS: The risk
      of nodal metastases was analysed retrospectively depending on the depth of
      submucosal invasion, size of the tumour, and other clinicopathological findings.
      MAIN OUTCOME MEASURES: The degree of submucosal invasion, size of the tumour, and
      incidence of lymph node metastasis. RESULTS: 15/104 patients (14%) had lymph node
      metastases. No patient in whom submucosal invasion was less than 500 microm or
      tumour was less than 15 mm in diameter developed lymph node metastases. Fewer
      patients had lymphatic permeation (37/89) and venous involvement (21/89) in the
      group without lymph node metastases. CONCLUSION: These data seem to support the
      hypothesis that early, minimally invasive, gastric cancer measuring < 15 mm in
      diameter could be treated by endoscopic mucosal or local resection, and
      gastrectomy with lymphadenectomy might be unnecessary.

PMID- 11316406
TI  - Endoscopic sphincterotomy in acute gallstone pancreatitis: a prospective study of
      the late outcome.
AB  - OBJECTIVE: To describe the outcome after acute biliary pancreatitis in patients
      treated during the acute attack by endoscopic sphincterotomy without
      cholecystectomy. DESIGN: Prospective observational study. SETTING: University
      hospital, Norway. SUBJECTS: 130 patients with gallstones and acute pancreatitis.
      In 62 patients with common bile duct stones the bile duct was cleared by
      sphincterotomy and stone extraction. The remaining 68 patients had prophylactic
      sphincterotomy. Cholecystectomy was not planned later. MAIN OUTCOME MEASURES:
      Incidence of recurrent acute pancreatitis and need for cholecystectomy. RESULTS:
      21 patients were dead or not available for the follow-up. Consequently 109
      patients were followed-up for a median of 39 months (range 23-62). One patient
      had recurrent pancreatitis. 20 patients had a cholecystectomy later for symptoms
      related to gallstone disease. Of the rest, 25 patients had moderate or mild
      gallstone-related symptoms. There was no difference in gallstone-related symptoms
      between those who had had stones in the bile duct and those who had not. 63
      patients had no symptoms related to gallstones. CONCLUSION: Endoscopic
      sphincterotomy during or immediately after acute gallstone pancreatitis resulted
      in half the patients being free of symptoms during the next three years.

PMID- 11316407
TI  - Conversion from laparoscopic to open appendicectomy: a possible drawback of the
      laparoscopic technique?
AB  - OBJECTIVE: To analyse the reasons for, and outcome of, conversion from
      laparoscopic to open appendicectomy and to identify factors that may predict the
      need for conversion. DESIGN: Subgroup analysis from a randomised multicentre
      study. SETTING: One university hospital and four county hospitals, Sweden.
      SUBJECTS: A total of 500 patients were randomised to laparoscopic (n = 244) or
      open (n = 256) appendicectomy. Thirty operations (12%) were converted to open
      appendicectomy. MAIN OUTCOME MEASURES: Reasons for conversion, outcome, and
      preoperative predictive variables. RESULTS: Difficult anatomy or the presence of
      an abscess were the main reasons for conversion (25/30). The incidence of
      perforated appendicitis was higher among patients who required conversion
      compared with both the open and laparoscopic group. Operating time, anaesthetic
      time, and duration of hospital stay were longer after conversion. Time to full
      recovery and length of sick leave were also longer, except for patients with
      perforated appendicitis. There was no difference in the complication rate. No
      predictive factors were identified. CONCLUSION: The main reasons for conversion
      were difficult anatomy and the presence of an abscess. After conversion patients
      recovered more slowly than those operated on laparoscopically or by primary open
      operation.

PMID- 11316408
TI  - Peritoneal cultures and antibiotic treatment in patients with perforated
      appendicitis.
AB  - OBJECTIVE: To question the common practice of sending material for
      microbiological examination during appendicectomy for perforated appendixes.
      DESIGN: Uncontrolled retrospective study. SETTING: Teaching hospital, Israel.
      SUBJECTS: 89 patients who had their perforated appendixes removed. INTERVENTIONS:
      Appendicectomy and antibiotic treatment. MAIN OUTCOME MEASURE: Whether a change
      in antibiotic regimen was required after bacteriological identification of
      bacteria isolated during the operation. RESULTS: In only 43 of the cultures (48%)
      taken during the operation were bacteria grown, and these were mainly Escherichia
      coli. In 65 patients (73%) there was no need to change the previously initiated
      antibiotic regimen, and in 23 (26%) it was changed purely on clinical grounds. In
      only one patient (1%) was the change the consequence of microbiological testing,
      as the organisms identified in 42 of the 43 cultures (98%) were sensitive to at
      least one of the antibiotics that had already been given. CONCLUSION: The
      practice of culturing samples taken from a ruptured appendix is redundant,
      because the antibiotic that has already been initiated is effective in most of
      the patients and the decision to modify the therapeutic regimen is dominated by
      clinical considerations.

PMID- 11316409
TI  - Peritoneal cultures and antibiotic treatment in patients with perforated
      appendicitis.

PMID- 11316410
TI  - Dynamic sonography with provocation of pain for diagnosis of symptomatic mobile
      kidneys.
AB  - OBJECTIVE: To evaluate the results of nephropexy in patients with a diagnosis of
      symptomatic mobile kidney that had been established by dynamic sonography with
      provocation of pain. DESIGN: Prospective study. SETTING: University hospital,
      Sweden. SUBJECTS: 19 consecutive patients with symptomatic right-sided mobile
      kidney and 6 controls who had urographically mobile kidneys but no pain.
      INTERVENTIONS: Dynamic sonography and dislocation of the kidney by manipulation.
      All 19 patients experienced pain on manipulation and the 6 controls did not. The
      19 patients were treated by nephropexy and followed for at least four years
      postoperatively. MAIN OUTCOME MEASURE: Relief of pain after nephropexy. RESULTS:
      In 16/19 patients the pain was relieved by nephropexy. CONCLUSION: Dynamic
      ultrasound is useful in correlating the abnormal position of the kidney with
      pain, and successfully indicates those patients whose symptoms will be relieved
      by nephropexy.

PMID- 11316411
TI  - Floating kidneys: fact or fiction?

PMID- 11316412
TI  - Role of the L-arginine/nitric oxide pathway in renal ischaemia-reperfusion in
      rats.
AB  - OBJECTIVE: To study the role of the L-arginine/nitric oxide (NO) pathway during
      renal ischaemia-reperfusion in rats. DESIGN: Randomised experimental study.
      SETTING: Teaching hospital, Brazil. ANIMALS: 97 male Wistar rats randomly
      assigned to 4 groups for the assessment of renal dysfunction and to 6 groups for
      the assessment of the oxidative stress induced on renal cell membranes by
      ischaemia-reperfusion. INTERVENTIONS: The animals underwent sham-operation or
      renal ischaemia-reperfusion (n = 9 each) with or without pretreatment with L
      arginine (a NO donor) or L-NAME (N(omega)-nitro-L-arginine methyl ester--an
      inhibitor of NO production) (n = 10 each). MAIN OUTCOME MEASURES: Serum
      creatinine concentrations and oxidative stress by chemiluminescence initiated by
      the tert-butyl hydroperoxide technique. RESULTS: Renal ischaemia-reperfusion
      significantly worsened renal dysfunction and increased oxidative stress in the
      ischaemia-reperfusion group after 24 and 96 hours of reperfusion compared with
      the control group (p < 0.05). Pretreatment with L-NAME slightly but not
      significantly increased serum creatinine concentrations after 24 and 96 hours of
      reperfusion together with activity of reactive oxygen species during renal
      ischaemia-reperfusion. L-arginine also significantly protected renal function and
      reduced the increment in the amount of chemiluminescence induced by giving L-NAME
      during 24 and 96 hours of reperfusion (p < 0.05). CONCLUSION: The L-arginine/NO
      pathway seems to have a slightly protective effect on the kidney after renal
      ischaemia-reperfusion injury in rats. These results need to be confirmed by
      studies in human beings.

PMID- 11316413
TI  - Successful management of an anastomotic leak after oesophagectomy with a graft of
      human dura mater.

PMID- 11316414
TI  - Isolated blunt traumatic rupture of gallbladder.

PMID- 11316415
TI  - Change in serum oestradiol and testosterone concentrations after mastectomy for
      breast cancer with high aromatase activity.

PMID- 11316416
TI  - "Operative monitoring of hand and axillary temperature during endoscopic superior
      thoracic sympathectomy for the treatment of palmar hyperhidrosis".

PMID- 11316417
TI  - cDNA cloning of two gonadotropin beta subunits (GTH-Ibeta and -IIbeta) and their
      expression profiles during gametogenesis in the Japanese flounder (Paralichthys
      olivaceus).
AB  - To clarify the profiles of two distinct gonadotropin (GTH-I and -II) mRNA levels
      during gametogenesis in a multiple spawner, the Japanese flounder (Paralichthys
      olivaceus), the cDNAs encoding GTH-Ibeta and -IIbeta from the pituitary gland
      have been cloned and sequenced. The nucleotide sequence of GTH-Ibeta was 542 bp
      long, encoding 120 amino acids, and that of GTH-IIbeta was 554 bp long, encoding
      145 amino acids. In females, Northern blot analysis has revealed that relative
      mRNA levels of GTH-Ibeta and -IIbeta were low in immature fish, showed a gradual
      increase with ovarian development, and reached the highest level at the
      maturation stage. Both GTH-Ibeta and -IIbeta mRNA levels were highly correlated
      with gonadosomatic index (GSI) values and with circulating estradiol-17beta and
      testosterone (T) levels. In males, the mRNA levels of GTH-Ibeta increased with
      the increase in GSI values and in circulating 11-ketotestosterone and T levels,
      whereas the mRNA levels of GTH-IIbeta did not show any correlation with GSI
      values and with circulating steroid levels, suggesting a difference in regulatory
      mechanisms of GTH-I and -II synthesis in males. The similar changes in GTH-Ibeta
      and -IIbeta mRNA levels during oogenesis are considered to be characteristic of
      GTH synthesis in multiple spawners, differing from the differential changes
      reported in annual spawners such as salmonids.

PMID- 11316418
TI  - Effect of an acute glucose overload on Islet cell morphology and secretory
      function in the toad.
AB  - The aim of this work was to study the effect of induced hyperglycemia on islet
      cell mass and insulin secretion in normal toads. Immunolabeled beta cell area,
      replication (bromodeoxyuridine) and apoptosis (propidium iodide) rate, islet
      neogenesis (cytokeratin), and insulin secretion in vitro were measured in adult
      male specimens of Bufo arenarum during and after interruption of the injection of
      either a 50% glucose solution (2 g/100 g) or its vehicle for 4 days. Glucose
      administration caused hyperglycemia (122.6 +/- 16.7 and 508.3 +/- 115.9 mg/dl vs
      23.5 +/- 1.26 and 22.8 +/- 1.8 mg/dl, at days 3 and 5, respectively, P < 0.05)
      and a significant decrease in the number of islets/mm(2) (day 3: 9.7 +/- 0.9 vs
      3.3 +/- 0.4, P < 0.05; day 5: 9.4 +/- 0.8 vs 7.4 +/- 0.6; day 9: 9.6 +/- 0.9 vs
      6.2 +/- 0.4, P < 0.05) and in the percentage of immunolabeled beta cell area (day
      3: 2.07 +/- 0.2 vs 0.5 +/- 0.1%, P < 0.05; day 5: 1.8 +/- 0.1 vs 0.6 +/- 0.1%;
      day 9: 1.7 +/- 0.1 vs 0.7 +/- 0.1%, P < 0.05). Glucose-injected animals had a
      simultaneous significantly higher percentage of BrdU-labeled beta cells (day 3:
      0.46 +/- 0.02 vs 0.23 +/- 0.03%; day 5: 0.54 +/- 0.13 vs 0.22 +/- 0.02%; day 9:
      0.61 +/- 0.0 vs 0.27 +/- 0.05%, P < 0.05) and cytokeratin-labeled endocrine cells
      (day 3: 0.21 +/- 0.06 vs 0.01 +/- 0.00%; day 5: 0.17 +/- 0.06 vs 0.01 +/- 0.01%;
      day 9: 1.25 +/- 0.2 vs 0.01 +/- 0.008%, P < 0.05) and a higher rate of apoptotic
      beta cells (day 3: 0.14 +/- 0.04 vs 0.05 +/- 0.02%; day 5: 0.4 +/- 0.06 vs 0.05
      +/- 0.2, P < 0.05; day 9: 0.47 +/- 0.04 vs 0.06 +/- 0.03, P < 0.05). Comparable
      amounts of insulin were secreted in vitro by both groups in response to 2 mM
      glucose, whereas there was a significantly reduced response to 8 mM glucose in
      treated animals (day 3: 73 +/- 12 vs 165 +/- 20%; day 5: 74 +/- 11 vs 204 +/-
      18%, P < 0.05). This decreased response to high glucose reverted to normal after
      removal of the glucose injection. These results show for the first time that
      short-term hyperglycemia triggers marked morphological and transient secretory
      changes in the toad pancreas similar in part to those elicited in the pancreas of
      several mammals. As with other results previously reported, these results support
      the usefulness of the toad as an alternative easily handled model to study the
      growth and secretory function of the endocrine pancreas.

PMID- 11316419
TI  - Changes in gonadal and adrenal steroid levels in the leatherback sea turtle
      (Dermochelys coriacea) during the nesting cycle.
AB  - The reproductive endocrinology of nesting leatherback turtles (Dermochelys
      coriacea) was studied during the 1996-1997 and 1997-1998 nesting seasons at Los
      Baulas National Park, Playa Grande, Costa Rica. Blood samples were collected from
      nesting females throughout the season. Females were observed to nest up to 10
      times during the nesting season. Plasma steroids were measured by
      radioimmunoassay and total plasma calcium was measured by flame atomic absorption
      spectrophotometry. Plasma testosterone and plasma estradiol levels declined
      throughout the nesting cycle of the female. Testosterone declined from a mean of
      10.18 +/- 0.77 ng/ml at the beginning of the nesting cycle to 1.73 +/- 0.34 ng/ml
      at the end of the nesting cycle. Estradiol declined in a similar manner, ranging
      from a mean of 190.95 +/- 16.80 pg/ml at the beginning of the nesting cycle to
      76.52 +/- 12.66 pg/ml at the end of the nesting cycle. Plasma progesterone and
      total calcium levels were relatively constant throughout the nesting cycle. Lack
      of fluctuation of total calcium levels, ranging from a mean high of 97.46 +/-
      11.37 microg/ml to a mean low of 64.85 +/- 11.20 microg/ml, further suggests that
      vitellogenesis is complete prior to the arrival of the female at the nesting
      beach. Clutch size (both yolked and yolkless eggs) did not vary over the course
      of the nesting cycle.

PMID- 11316420
TI  - Receptors for insulin-like growth factor-I (IGF-I) predominate over insulin
      receptors in skeletal muscle throughout the life cycle of brown trout, Salmo
      trutta.
AB  - Insulin and IGF-I binding has been studied in brown trout (Salmo trutta) wheat
      germ agglutinin semipurified receptors from embryos (organogenesis), larvae (yolk
      sac), juveniles (2.98 +/- 0.21 g bw) and adults (111.6 +/- 6.92 and 522 +/- 53 g
      bw). Embryos and larvae were sampled at 5 and 12 weeks after fertilization
      (December 1999 and February 2000) and juvenile and adults were taken
      simultaneously (July 1999) and under the same feeding conditions to minimize
      potential nutritional and seasonal effects. Insulin receptor number was maximal
      at 12 weeks (144 fmol/mg glycoprotein) and progressively decreased in subsequent
      samplings. No alterations in affinity were detected (K(d) range, 0.21-0.32 nM)
      and changes in number of receptor paralleled changes in total specific binding.
      IGF-I receptor number was highest at 5 weeks (1044 fmol/mg) and was significantly
      higher than values for insulin in all samplings. The affinity of IGF-I receptor
      did not change (K(d) range, 0.11-0.18 nM) but was consistently higher than that
      for the insulin receptor. A more rapid decrease of IGF-I binding and receptor
      number was found with age. However, the ratio of insulin/IGF-I binding
      established in 12-week-old larvae (0.18 +/- 0.01) was thereafter maintained at
      very similar values in juveniles and adults (0.15-0.17). Tyrosine kinase activity
      (TKA) for insulin receptors ranged between 136 and 183% and there were no
      significant changes with age. For the IGF-I receptor, TKA ranged from 174 to 281%
      and was significantly higher in 5-week-old larvae coincident with the highest
      levels of receptor number and declined gradually in parallel with binding levels.
      In conclusion, the greater abundance of IGF-I receptors during embryonic and
      larval development is maintained throughout juvenile and adult stages. This would
      suggest a key role for IGF-I in the growth and metabolism of trout muscle.

PMID- 11316421
TI  - Longitudinal gonadal steroid excretion in free-living male and female meerkats
      (Suricata suricatta).
AB  - Slender-tailed meerkats (Suricata suricatta) are small, diurnal, cooperatively
      breeding mongooses of the family Herpestidae. A prerequisite to fully
      understanding the mating system of meerkats is the development of a normative
      reproductive-endocrine database. This study examined longitudinal gonadal steroid
      excretion in all adult and juvenile individuals of both sexes within a social
      group of free-living meerkats sampled across an entire breeding season. The
      specific objectives of this study were to (1) validate noninvasive (fecal and
      urinary) gonadal steroid hormone monitoring techniques in male (testosterone) and
      female (estrogens, progestagens) meerkats; (2) test the feasibility of using
      these noninvasive methods under field conditions; (3) characterize the endocrine
      correlates associated with the female reproductive cycle, including estrus,
      gestation, and postpartum estrus; (4) examine longitudinal androgen excretion in
      males; and (5) determine whether social status (i.e., dominant versus
      subordinate) affected gonadal steroid excretion. In females, the results
      demonstrated the physiological validity of noninvasive monitoring in meerkats by
      corresponding excretory hormone concentrations to major reproductive events
      (i.e., estrous, pregnancy, parturition). Hormone excretory patterns during
      estrous intervals suggested possible mechanisms whereby reproductive suppression
      may operate in female meerkats. In males, androgen excretion did not correspond
      to changes in reproductive and aggressive behaviors, suggesting that dominance,
      and hence breeding access to females, was not regulated strictly by gonadal
      steroid production. The consistency in androgen excretion among male meerkats
      indicated that reproductive suppression may be mediated by behavioral (i.e.,
      intermale aggression) rather than physiological (i.e., depressed spermatogenesis)
      mechanisms.

PMID- 11316422
TI  - Biotransformation and disposition of testosterone in the eastern mud snail
      Ilyanassa obsoleta.
AB  - Elevated testosterone levels have been reported to be associated with imposex
      (pseudohermaphroditism), the superimposition of male characteristics such as a
      penis and vas deferens on female gonachoristic snails. Tributyltin (TBT), a
      marine biocide in anti-fouling paints, is a known causal agent of imposex.
      Evidence suggests that imposex is elicited by TBT-mediated changes in the
      biotransformation and disposition of testosterone. To identify potential targets
      of TBT in gastropod species susceptible to imposex, biotransformation and
      disposition of testosterone in normal individuals must first be characterized.
      Nonimposex mud snail, Ilyanassa obsoleta, readily extracted [(14)C]testosterone,
      added to aqueous media, and converted the testosterone to at least five apolar
      conjugates designated AP1 through AP5. All were retained by the organisms. No
      significant amount of [(14)C]testosterone was retained or eliminated as polar
      metabolites. Following enzymatic hydrolysis of the most abundant metabolite
      (AP1), free fatty acids and [(14)C]testosterone were liberated. Furthermore, AP1
      was produced when homogenized snail tissue was incubated with [(14)C]testosterone
      and oleoyl coenzyme A or palmitoyl coenzyme A. These results indicate that AP1,
      which represents over 70% of the testosterone biotransformation products, is a
      fatty acid ester of testosterone. Apolar metabolites AP2-AP5 might represent
      testosterone derivatives that are multiply conjugated to fatty acid molecules.
      Fatty acid conjugates of testosterone have not been previously described in the
      gastropods. The esterification of testosterone to fatty acids might be a
      mechanism where by steroid titers are regulated and could represent a target of
      TBT toxicity.

PMID- 11316423
TI  - Stress-induced catecholamine changes in the hemolymph of the oyster Crassostrea
      gigas.
AB  - The stress response is a series of coordinated physiological reactions increasing
      an organism's capacity to maintain homeostasis in the presence of threatening
      agents. This fundamental process is known to involve hormonal signaling to
      rapidly modulate key physiological functions in vertebrates, but data are lacking
      concerning neuroendocrine responses to stress in invertebrates. The present study
      examined circulating catecholamine (CA) responses to stress in oysters.
      Mechanical disturbances (consisting of shaking the animals) and temperature or
      salinity variations were applied to the animals because these three types of
      stressors are commonly encountered by oysters in aquaculture or in their natural
      habitat. Results show that both circulating noradrenaline (NA) and dopamine (DA)
      concentrations increased in response to stress. The catecholaminergic response to
      acute mechanical stressors was rapid (less than 5 min), transient (a return to
      basal CA levels was observed after 60-90 min), and reflected both the intensity
      and duration of the perturbation. In contrast, responses to temperature and
      salinity variations were long lasting (up to 72 h). CA concentrations varied from
      1.61 +/- 0.30 ng NA/ml and 0.41 +/- 0.05 ng DA/ml to maximal values of 22.07 +/-
      0.97 ng NA/ml and 2.24 +/- 0.19 ng DA/ml. Such CA concentrations are known to
      induce physiological responses in bivalves, suggesting that stress-induced NA and
      DA changes exert a regulatory function in oysters.

PMID- 11316424
TI  - Behavioral and hormonal effects of exogenous vasotocin and corticosterone in the
      green treefrog.
AB  - Vasotocin (AVT) promotes courtship in a wide range of vertebrates. However, this
      effect is not independent of steroid hormones. For example, androgens may work in
      concert with AVT and corticosterone (CORT) may work to oppose AVT action. In
      frogs, AVT promotes calling, and in some species, CORT inhibits calling. In
      addition, androgens are known to modulate AVT in the brain, and CORT may depress
      androgen secretion. Previous work in amphibians has suggested that AVT promotes
      courtship by overcoming a CORT-mediated stress response. Possible behavioral and
      hormonal interactions among AVT, CORT, and androgens were investigated in wild,
      free-living green treefrogs (Hyla cinerea). Saline, AVT, CORT, or a combination
      of AVT and CORT were administered to calling males, and several measures of
      spontaneous calling were evaluated for 1.5 h following injection. Plasma
      testosterone, dihydrotestosterone, and CORT were also measured. Saline-injected
      males had low CORT levels, and AVT and CORT injection elevated plasma CORT
      levels. AVT increased the likelihood of calling, but, in males who did call, AVT
      did not influence latency to call or how often they were observed calling. Very
      few saline-injected males resumed calling after injection, and therefore a CORT
      effect was only detectable in AVT-injected males. CORT inhibited calling in AVT
      injected males only at the highest dose of CORT (40 microg); lower levels of CORT
      were unsuccessful at inhibiting AVT-induced calling. AVT appeared to have a
      specific effect on calling motivation. Further, the data suggest that
      disinhibition of a CORT response is not the primary mechanism by which AVT
      increases calling. In addition, CORT injection reduced endogenous androgen
      levels. Finally, endogenous androgens were negatively correlated with latency to
      begin calling, suggesting that they may have a positive effect on calling. These
      data indicate that AVT has positive effects on calling but provide only weak
      evidence that CORT inhibits courtship in this species.

PMID- 11316425
TI  - Nitric oxide, a potent vasodilator of the aortic anastomosis in the estuarine
      crocodile, Crocodylus porosus.
AB  - The effects of five neuropeptides (CGRP, SOM, SP, NPY, VIP), L-NAME (nitric oxide
      synthase inhibitor), and adrenaline on the contractile tone of the aortic
      anastomosis in the estuarine crocodile, Crocodylus porosus, were investigated.
      None of the neuropeptides, which had previously been found to be present in the
      aortic anastomosis, had any direct effect on the tension developed by ring
      preparations. L-NAME itself significantly increased the basal tone of the
      vascular ring preparations, suggesting a tonic release of nitric oxide in the
      preparation. Adrenaline produced concentration-dependent vasoconstrictions that
      were counteracted by profound reflex vasodilatations that were susceptible to
      blockade by L-NAME. Immunohistochemistry revealed the presence of nitric oxide
      synthase and tyrosine hydroxylase-containing (indicating the presence of a
      adrenergic innervation) nerve fibres in the adventitia and adventitio-medial
      border of the aortic anastomosis. These data demonstrate opposing actions of
      adrenaline and nitric oxide on the vascular smooth muscle in the anastomosis of
      the C. porosus. The morphology of the anastomosis, with the extremely thick
      muscular vessel wall, suggests a sphincter-like function for this vessel that
      could be controlled mainly by adrenergic and nitrergic mechanisms.

PMID- 11316426
TI  - Plasma corticosterone in nestling american kestrels: effects of age, handling
      stress, yolk androgens, and body condition.
AB  - The effects of age, handling-induced stress, yolk androgens, and body condition
      on plasma corticosterone levels were investigated in free-living nestling
      American kestrels, Falco sparverius, a semialtricial falcon species. In an
      observational study, corticosterone levels varied with age and handling time.
      Specifically, corticosterone was low until age 15 days and then rose from age 20
      through 25 days. Nestlings as young as age 10 days showed a handling-induced rise
      in corticosterone. Neither sex nor hatching order of the nestling affected
      corticosterone levels. Concentrations of maternally derived yolk androgens have
      previously been shown to be lower in first-laid than in later-laid eggs in the
      clutch. In an experimental study, androgens were injected into the yolk of the
      first-laid egg to elevate its levels to those of later-laid eggs, a treatment
      that substantially reduces nestling body condition compared with that of
      controls. Yolk androgen treatment elevated posthatching corticosterone levels
      compared with those of controls, and corticosterone levels were negatively
      correlated with body condition. These findings indicate that even very young,
      developing birds can show stress-induced increases in corticosterone and that age
      related changes in corticosterone secretion may be modified by body condition and
      maternal effects such as yolk androgen deposition. The short- and long-term
      consequences of high glucocorticosteroid levels in young, developing vertebrates
      are largely unknown.

PMID- 11316427
TI  - Quantification of growth hormone receptor extra- and intracellular domain gene
      expression in chicken liver by quantitative competitive RT-PCR.
AB  - The very sensitive competitive reverse transcription-polymerase chain reaction
      (RT-PCR) was used to investigate the expression of the extracellular (GHRe) and
      intracellular (GHRi) parts of the growth hormone receptor (GHR) in the liver
      tissue of chickens. Two competitors (internal standards), pGHRi MUT and pGHRe
      MUT, specific to the GHRi and GHRe genes, respectively, were constructed by site
      specific mutagenesis. The internal standards defined PCR products of 394 bp for
      the pGHRi MUT and 330 bp for the GHRe MUT. These were used as competitors to the
      wild-type GHRi or GHRe which defined PCR products of 382 and 328 bp,
      respectively. Coamplification, under standardized conditions, of the native RNA
      in competition with serial dilutions of the mutant RNA in the same PCR reaction
      followed by enzymatic digestion produced the expected sizes of internal standard
      cDNA and predicted target cDNA. Expression levels of GHRe and GHRi were
      determined from standard curves generated. The method was sensitive enough to
      detect expressions down to picogram levels. Applying this method, the effect of
      GH and T(3) injection on GHRe and GHRi mRNA expression was determined in the
      liver of adult female Hisex birds and 1-day-old normal and dwarf chickens.
      Intravenous GH injection (25 microg/kg body weight) increased plasma levels of GH
      in Hisex birds after 10 min but rapidly decreased at 60 min followed by an
      increase in T(3). GH injection significantly increased the expression of the GHRe
      60 min after injection but not at 10 min, when the GH level in plasma was high.
      In the liver of saline-treated dwarf (dw) and nondwarf (Dw) chicks, the level of
      expression of GHRe was similar in both strains despite disparate levels of basal
      GH and T(3). However, the level of GHRi was higher in Dw than in dw chicks.
      Although GH levels increased in both strains after intravenous GH injection (250
      microg/kg body wt), the expression of GHRe in both strains was unaffected.
      However, the mRNA for the GHRi was significantly depressed by injection in the Dw
      but unaffected in dw chicks. Intravenous injection of T(3) (0.5 and 5 microg/kg
      body wt) increased plasma levels in both strains but caused depression of GHRi in
      Dw but not in dw chicks. T(3) injections had no effect on GHRe in either Dw or dw
      chicks. It is concluded that the expression of the GHRe in adult chickens is GH
      regulated either directly or indirectly. In contrast, in 1-day-old chicks, GH or
      T(3) had no effects on the GHRe but regulated the expression of GHRi in Dw
      chicks, whereas in dwarf chicks both had no effect on GHRe or GHRi expression. It
      is postulated that GHRe and GHRi gene expression may be regulated by different
      agonists/antagonists in different strains and depending on the age of the
      chicken.

PMID- 11316428
TI  - Observations on serum 25-hydroxyvitamin D and calcium concentrations from wild
      caught and captive neotropical bats, Artibeus jamaicensis.
AB  - Most bats of the suborder Microchiroptera are nocturnal, actively avoid sunlight,
      and eat mineral-poor diets. In those bats previously studied with respect to
      mineral metabolism, extensive bone remodeling occurs, and it has been suggested
      that calcium has been an important constraint on reproduction. There have been no
      previous studies of vitamin D or its metabolites in microchiropteran bats with
      respect to calcium metabolism. Reported is the utilization of current advances
      for the determination of serum levels of the vitamin D metabolite 25
      hyroxyvitamin D (25-OH-D) in a neotropical bat, Artibeus jamaicensis. Serum from
      wild-caught animals contained low levels of 25-OH-D (5.6 +/- 3.0 ng/ml, n = 8).
      Bats maintained on a vitamin-D-supplemented diet had higher serum 25-OH-D levels
      and when the diet containing vitamin D was discontinued, mean serum 25-OH-D
      levels declined significantly after 6 months. Serum calcium concentrations in
      wild-caught bats (8.5 +/- 0.4 mg%) showed very little variation and were not
      significantly different in any of the vitamin-D-supplemented animals. A pairwise
      correlation analysis between 25-OH-D and serum calcium levels revealed no linear
      correlation. The results indicate either that 25-OH-D does not appear to play a
      key role or that low levels of 25-OH-D may be adequate in regulating serum
      calcium levels in this bat.

PMID- 11316430
TI  - Preparation of nonradioactive probes for in situ hybridization.
AB  - In situ hybridization (ISH) enables the precise localization of RNA targets and
      provides an avenue to study the temporal and spatial patterns of expression of
      specific genes. ISH has evolved from being an esoteric technique to one that is
      routinely used by researchers in many areas of research. A major driving force
      has been the development of numerous nonisotopic labeling and signal detection
      methods. Historically, radioactive probes and autoradiography provided
      sensitivity that was unattainable with nonisotopic probes. But the long exposure
      times required for signal detection and the perceived dangers associated with
      radioactivity limit its use. Advances in nonisotopic detection systems have
      overcome many of the limitations associated with using radiolabeled probes. One
      of the most significant contributions from nonisotopic methods is the ability to
      discriminate between multiple nucleic acid sequences simultaneously.

PMID- 11316431
TI  - Nonradioactive in situ hybridization to xenopus tissue sections.
AB  - We describe a protocol for the localization of specific messenger RNAs in Xenopus
      laevis embryo tissue sections using a nonradioactive detection method. After
      fixation, embryos are embedded in paraffin wax, sectioned, mounted on slides, and
      subjected to a series of prehybridization treatments which improve the
      accessibility of the probe to the target mRNA and reduce nonspecific binding.
      These treatments are followed by hybridization in situ with single-stranded
      antisense RNA probe generated by in vitro transcription and labeled with
      digoxigenin. The hybridization products are detected with preabsorbed alkaline
      phosphatase-coupled digoxigenin antibody and subsequently localized using a
      chromogenic substrate that generates a colored precipitate at the hybridization
      site. The nonradioactive in situ hybridization method we describe is reproducible
      and has a detection sensitivity akin to those methods that use antisense RNA
      probes labeled with radioisotopes; however, it is faster, safer, and easier to
      perform. Sectioning of prestained whole-mount X. laevis embryos does not always
      show the complete expression pattern of many genes, particularly those in deep
      endodermal structures, due to inadequate probe penetration. Therefore thorough
      analysis of gene expression patterns often requires in situ hybridization on
      presectioned material whereby probe has equal accessibility to all tissue.

PMID- 11316432
TI  - In situ hybridization: use of 35S-labeled probes on paraffin tissue sections.
AB  - The following protocol is for radioactive in situ hybridization detection of RNA
      using paraffin-embedded tissue sections on glass microscope slides. Steps taken
      to inhibit RNase activity such as diethyl pyrocarbonate (DEPC) treatment of
      solutions and baked glassware are unnecessary. The tissue is fixed using 4%
      paraformaldehyde, hybridized with (35)S-labeled RNA probes, and exposed to
      nuclear-track emulsion. The entire procedure takes 2-3 days prior to
      autoradiography. The time required for autoradiography is variable with an
      average time of 10 days. Parameters that affect the length of the autoradiography
      include: (1) number of copies of mRNA in the tissue, (2) incorporation of label
      into the probe, and (3) amount of background signal. Additional steps involved in
      the autoradiography process, including development of the emulsion, cleaning of
      the microscope slides, counterstaining of the tissue, and mounting coverslips on
      the microscope slides, are discussed. In addition, a general guide to the
      interpretation of the in situ results is provided.

PMID- 11316433
TI  - In situ hybridization to mRNA of Arabidopsis tissue sections.
AB  - In situ hybridization detection of mRNA is an essential tool for understanding
      regulation of gene expression in cells and tissues of different organisms. Over
      the years, numerous in situ protocols have been developed ranging from whole
      mount techniques that allow fast transcript localization in intact organs to high
      resolution methods based on the electron microscopic detection of mRNAs at the
      subcellular level. Here, we present a detailed protocol for the detection of
      mRNAs in plant tissues using radiolabeled single-stranded RNA probes.
      Hybridizations are carried out on tissue sections of paraffin- and plastic
      embedded plant tissues. Although this in situ protocol is appropriate for plant
      tissues in general, it has been optimized for Arabidopsis thaliana. Variations on
      the procedure, required to obtain optimal results with different Arabidopsis
      tissues, are described.

PMID- 11316434
TI  - Whole-mount in situ hybridization to mouse embryos.
AB  - The mouse is well-established as the major animal model for the study of
      mammalian development. Rapid progress in large-scale cDNA and also genomic
      sequencing projects is identifying new mouse genes at an unprecedented rate. As a
      first step toward understanding the function of these novel genes, it is
      important to determine their developmental expression pattern. Here we provide a
      reliable, sensitive method for whole-mount in situ hybridization using the mouse
      embryo.

PMID- 11316435
TI  - Combined whole-mount in situ hybridization and immunohistochemistry in avian
      embryos.
AB  - The whole-mount in situ hybridization process has revolutionized the study of
      gene expression in the embryo. This procedure allows extremely sensitive
      detection of RNA transcripts and excellent spatial resolution. Numerous
      experiments benefit from the detection of more than one marker molecule in the
      same experimental embryo. While antisense RNA probes are extremely useful and
      methods for two-color in situ hybridization are available, antibodies recognizing
      specific protein species can help to expand the range of markers detected. Here
      we present a protocol that permits the simultaneous localization of RNA
      transcripts and immunocytochemical localization of proteins in the chick embryo.

PMID- 11316436
TI  - Double in situ hybridization techniques in zebrafish.
AB  - Over recent years many genes expressed in zebrafish embryos have been cloned and
      a first step in their analysis is the determination of the spatial and temporal
      expression patterns of their transcripts by in situ hybridization. It is often
      necessary to relate the expression pattern to that of other genes expressed at
      the same period of development. Transcripts from different genes may be expressed
      in complementary or overlapping domains. The pattern of expression of different
      genes can be related by performing in situ hybridization on consecutive sections
      of tissue but it is also possible to perform hybridizations with two probes and
      to visualize the signals separately in the same tissue. Occasionally it is also
      possible to combine in situ hybridization with immunocytochemistry to localize
      tissue-specific antigens. Methods developed for performing these types of
      analyses in zebrafish are described in this article.

PMID- 11316437
TI  - One-, two-, and three-color whole-mount in situ hybridization to Drosophila
      embryos.
AB  - This article contains detailed protocols for the localization of mRNA transcripts
      within whole Drosophila embryos. The procedures are based on the use of
      digoxigenin-, fluorescein-, and biotin-labeled antisense RNA probes for
      nonradioactive detection of transcripts. The labels are visualized in situ by
      differently colored water-insoluble precipitates using alkaline phosphatase- or
      beta-galactosidase-based immunoassays. First, a basic method is described that
      allows detection of transcript distribution(s) of one or more genes using the
      same color precipitate. Second, a sequential alkaline phosphatase detection
      method is presented that permits the visualization of two or three independent
      transcript patterns in multiple colors in the same embryo. Third, a shortened two
      color in situ hybridization protocol is provided that employs a combination of
      beta-galactosidase and alkaline phosphatase colorimetric reactions for
      differential detection. The two-color in situ hybridization methods work equally
      well in Drosophila and zebrafish embryos and may therefore also be adaptable to
      other species.

PMID- 11316463
TI  - Changes in human lymphocyte subpopulations in tonsils and regional lymph nodes of
      human head and neck squamous carcinoma compared to control lymph nodes.
AB  - BACKGROUND: Lymphoid tissues constitute basic structures where specific immune
      responses take place. This leads to the development of germinal centres (GCs),
      migration of cells and the generation of memory cells. Here, we have compared
      human tumour reactive lymph nodes and tonsils with control lymph nodes. RESULTS:
      The study by flow cytometry shows that in control lymph nodes the majority of
      cells were naive T-lymphocytes (CD45RA+/CD7+). In reactive nodes, although the
      percentage of CD45RO+ T cells remains constant, there is an increase in the
      number of B-lymphocytes, and a reduction in naive T cells. The percentage of
      cells expressing CD69 was similar in reactive nodes and in controls. In both
      cases, we have found two populations of B cells of either CD69- or CD69dull. Two
      populations of T cells, which are either negative for CD69 or express it in
      bright levels (CD69bright), were also found. The analysis of tissue sections by
      confocal microscopy revealed differences between control, tonsils and tumor
      reactive lymph nodes. In control lymph nodes, CD19 B cells are surrounded by a
      unique layer of CD69bright/CD45RO+ T cells. GCs from tonsils and from tumour
      reactive nodes are mainly constituted by CD19 B cells and have four distinct
      layers. The central zone is composed of CD69- B cells surrounded by
      CD69bright/CD45RO+ T cells. The mantle region has basically CD69dull B
      lymphocytes and, finally, there is an outer zone with CD69-/CD45RO+ T cells.
      CONCLUSIONS: Human secondary lymphoid organs react with an increase in the
      proportion of B lymphocytes and a decrease in the number of CD45RA+ T cells
      (naive). In tonsils, this is due to chronic pathogen stimulation, whereas in
      lymph nodes draining head and neck carcinomas the reaction is prompted by
      surrounded tumors. During this process, secondary lymphoid organs develop
      secondary follicles with a special organization of T and B cells in consecutive
      layers, that are described here by confocal microscopy. This pattern of cellular
      distribution may suggest a model of cell migration into the secondary lymphoid
      follicles.

PMID- 11316466
TI  - Fasciola hepatica: surfaces involved in movement of miracidia and cercariae.
AB  - Rapid freezing and substitution with fixative prior to scanning electron
      microscopy was used to demonstrate the pattern of beat and recovery of the cilia
      of free swimming miracidia of Fasciola hepatica. There were stages of
      dexioplectic metachronal co-ordination and the power stroke was approximately 15
      degrees anticlockwise from the anterior-posterior axis. Around the circumference
      of the body of the miracidia there were approximately 12 metachronal waves of
      power and recovery. Free-swimming cercariae were recorded by time-lapse
      photography and, after conventional fixation, by scanning electron microscopy.
      Cercarial tail-beats were to the posterior of the body in the lateral plane at a
      rate of 8 Hz. The tail has paired lateral ridges positioned to act as leading
      edges. There is an array of 32 sensory papillae on the mid-ventral surface of the
      tail. The tegument of the most distal part of the tail is described: it is free
      of sensory endings and the surface shows a spiral pattern.

PMID- 11316465
TI  - Inhibition of spontaneous induction of lambdoid prophages in Escherichia coli
      cultures: simple procedures with possible biotechnological applications.
AB  - BACKGROUND: Infections of bacterial cultures by bacteriophages are serious
      problems in biotechnological laboratories. Apart from such infections, prophage
      induction in the host cells may also be dangerous. Escherichia coli is a commonly
      used host in biotechnological production, and many laboratory strains of this
      bacterium harbour lambdoid prophages. These prophages may be induced under
      certain conditions leading to phage lytic development. This is fatal for further
      cultivations as relatively low, though still significant, numbers of phages may
      be overlooked. Thus, subsequent cultures of non-lysogenic strains may be infected
      and destroyed by such phage. RESULTS: Here we report that slow growth of bacteria
      decreases deleterious effects of spontaneous lambdoid prophage induction.
      Moreover, replacement of glucose with glycerol in a medium stimulates lysogenic
      development of the phage after infection of E. coli cells. A plasmid was
      constructed overexpressing the phage 434 cI gene, coding for the repressor of
      phage promoters which are necessary for lytic development. Overproduction of the
      cI repressor abolished spontaneous induction of the lambda(imm434) prophage.
      CONCLUSIONS: Simple procedures that alleviate problems with spontaneous induction
      of lambdoid prophage and subsequent infection of E. coli strains by these phages
      are described. Low bacterial growth rate, replacement of glucose with glycerol in
      a medium and overproduction of the cI repressor minimise the risk of prophage
      induction during cultivation of lysogenic bacteria and subsequent infection of
      other bacterial strains.

PMID- 11316464
TI  - Compulsive checking behavior of quinpirole-sensitized rats as an animal model of
      Obsessive-Compulsive Disorder(OCD): form and control.
AB  - BACKGROUND: A previous report showed that the open field behavior of rats
      sensitized to the dopamine agonist quinpirole satisfies 5 performance criteria
      for compulsive checking behavior. In an effort to extend the parallel between the
      drug-induced phenomenon and human obsessive-compulsive disorder (OCD), the
      present study investigated whether the checking behavior of quinpirole rats is
      subject to interruption, which is an attribute characteristic of OCD compulsions.
      For this purpose, the rat's home-cage was placed into the open field at the
      beginning or the middle of a 2-hr test. RESULTS: Introduction of the home-cage
      reduced checking behavior, as rats stayed inside the cage. After 40 min, checking
      resurfaced, as quinpirole rats exited the home-cage often. An unfamiliar cage had
      no such effects on quinpirole rats or saline controls. CONCLUSIONS: Checking
      behavior induced by quinpirole is not irrepressible but can be suspended. Results
      strengthen the quinpirole preparation as an animal model of OCD compulsive
      checking.

PMID- 11316467
TI  - Helminth communities in eels Anguilla anguilla from Adriatic coastal lagoons in
      Italy.
AB  - The composition and diversity of the total and intestinal component and infra
      communities were determined in eels Anguilla anguilla from three shallow lagoons
      on the Adriatic coast of Italy to determine whether the helminth communities
      would differ in composition and structure from those in eels from lagoons on the
      Tyrrhenian coast. The lagoons differed in respect of their management regimes and
      the extent of freshwater influx. Both freshwater and marine species of helminths
      were found in the eels in all three lagoons, but the freshwater component was
      richer in Valle Figheri. A suite of three digenean eel specialist species
      occurred in all three lagoons, of which any two members dominated each community.
      This conferred a high degree of similarity between the communities of the three
      lagoons. The same three species also dominated helminth communities in eels in
      lagoons along the Tyrrhenian coast of Italy, and compositional similarity levels
      were similar within and between western and eastern groups. Species richness was
      higher in the component communities of the eels of the Adriatic lagoons when
      compared to the Tyrrhenian ones, but diversity and dominance indices were of a
      similar order of magnitude and range. Intestinal helminth communities were richer
      and more diverse in two of the Adriatic lagoons because the proportion of eels
      with zero or one helminth species was, unusually, in the minority. It was
      nevertheless concluded that infracommunity structure was similar in eels from
      both western and eastern lagoons and that the hypothesis that it would differ in
      Adriatic lagoons could not be supported. The findings provide further evidence of
      the similarity in composition and structure of helminth communities in eels from
      coastal lagoons throughout Europe.

PMID- 11316468
TI  - Ultrastructure of the tegument of Saccocoelioides godoyi.
AB  - The tegument of adult Saccocoelioides godoyi Kohn & Froes, 1986 (Digenea:
      Haploporidae), specimens of which were collected from the intestine of the
      freshwater fish, Leporinus friderici (Bloch, 1794) (Anostomidae) from the
      reservoir of Itaipu Hydroelectric Power Station, Parana State, Brazil, was
      studied by transmission electron microscopy. The tegument comprises an external
      anucleate layer, covered by a surface plasma membrane and associated glycocalyx.
      The surface layer is bound by the basal plasma membrane and contains spines, two
      types of inclusion bodies and mitochondria. Tegumental cell bodies are located
      beneath the surface musculature and contain a single nucleus, cytoplasm with
      rough endoplasmic reticulum, mitochondria, ribosomes, and inclusion bodies
      similar to those found in the external layer. Cytoplasmic strands connect the
      cell bodies to the external surface layer, suggesting that the inclusion bodies
      are produced in these cells and pass up into the syncytium, as is known for other
      digeneans from experimental evidence.

PMID- 11316469
TI  - Influence of mouse strain, infective dose and larval burden in the brain on
      activity in Toxocara-infected mice.
AB  - Outbred LACA mice and inbred NIH mice were administered low (100 ova), medium
      (1000 ova), high (3000 ova) and trickle (4x250 ova) doses of Toxocara canis ova
      and the effect of infection on activity was examined with respect to: (i) the
      dose of ova administered and (ii) the number of larvae recovered from the brain.
      Larval recovery from the brain was significantly reduced in NIH mice compared to
      LACA mice for the 1000, 3000 and trickle doses. Mice from each strain were
      divided into larval intensity groupings based upon the number of larvae recovered
      from their brain. Activity for each mouse was measured pre- and post-infection by
      observing its behaviour in the home cage. Activity was assessed by monitoring six
      different independent categories of murine behaviour - ambulation, grooming,
      rearing, digging, climbing and immobility. Within each behavioural category, the
      duration of time spent at each behaviour per mouse within one thousandth of a
      second, the number of short bouts performed and the number of long bouts of
      behaviour performed were recorded over a 20 min period. Activity of LACA and NIH
      mice differed prior to infection. LACA mice spent more time immobile compared to
      NIH mice, which ambulated and climbed more. Variations in activity were also
      observed between groups of mice prior to infection. The effect of infection
      differed by strain, by dose and by larval intensity. Post-infection LACA mice
      became more immobile and ambulated less. NIH mice showed reduced immobility, but
      while ambulation decreased digging and climbing increased post-infection. Short
      bouts of activity remained unchanged among LACA mice post-infection but showed an
      increase for some behaviours in NIH mice.

PMID- 11316470
TI  - Relationship between three intensity levels of Toxocara canis larvae in the brain
      and effects on exploration, anxiety, learning and memory in the murine host.
AB  - Outbred LACA mice were administered low (100 ova), medium (1000 ova), high (3000
      ova) and trickle (4x250 ova) doses of Toxocara canis ova and the effect of
      infection was examined with respect to the number of larvae recovered from the
      brain and their behaviour. Recovery of larvae from the brain was generally low
      with the % recovery expressed in terms of the total dose administered being
      highest for the 3000 dose (6.1%) and 1000 dose (6%), followed by the 100 (4.4%)
      and trickle (3.5%) doses. The variation in larval recoveries was large between
      individual mice receiving similar doses. The level of infection in the brain was
      lower in mice receiving a multiple as opposed to an equivalent single dose of
      ova. Mice were then divided into three larval intensity groupings based upon the
      number of larvae recovered from their brain. The ranges for the groups were as
      follows: low intensity group, 0-15 larvae; moderate intensity group, 27-55
      larvae; high intensity group, 66-557 larvae. Three behavioural tests were carried
      out on control and infected mice. Exploration and response to novelty was
      examined using a 'T' maze and learning was investigated by means of a water
      finding task. Anxiety was measured using an elevated plus maze apparatus.
      Infected mice were less explorative and less responsive to novelty in the 'T'
      maze and this was particularly pronounced for the heavily infected mice. In the
      elevated plus maze, infected mice displayed reduced levels of anxiety to aversive
      and exposed areas of the maze, particularly in the case of the moderate and high
      intensity mice. There was evidence for impaired learning ability in the water
      task apparatus for moderate and high intensity mice. In general, the effects of
      infection on behaviour were more pronounced in the moderate and high intensity
      groups compared to the low intensity group.

PMID- 11316471
TI  - Fasciola gigantica: surface topography of the adult tegument.
AB  - Adult Fasciola gigantica are leaf-shaped with tapered anterior and posterior ends
      and measure about 35 mm in length and 15 mm in width across the mid section.
      Under the scanning electron microscope its surface appears rough due to the
      presence of numerous spines and surface foldings. Both oral and ventral suckers
      have thick rims covered with transverse folds and appear spineless. On the
      anterior part of the ventral surface of the body, the spines are small and
      closely-spaced. Each spine has a serrated edge with 16 to 20 sharp points, and
      measures about 20 microm in width and 30 microm in height. In the mid-region the
      spines increase in size (up to 54 microm in width and 58 microm in height) and
      number, especially towards the lateral aspect of the body. Towards the posterior
      end the spines progressively decrease in both size and number. The tegumental
      surface between the spines appears highly corrugated with transverse folds
      alternating with grooves. At higher magnifications the surface of each fold is
      further increased with a meshwork of small ridges separated by variable-sized
      pits or slits. There are three types of sensory papillae on the surface. Types 1
      and 2 are bulbous, measuring 4-6 microm in diameter at the base with nipple-like
      tips, and the type 2 also have short cilia. Type 3 papillae are also bulbous and
      of similar size but with a smooth surface. These sensory papillae usually occur
      in clusters, each having between 2 and 15 units depending on the region of the
      body. Clusters of papillae on the lateral aspect (usually types 1 and 2) and
      around the suckers (type 3) tend to be more numerous and larger in size. The
      dorsal side of the body exhibits similar surface features, but the spines and
      papillae appear less numerous and are smaller. Corrugation and invaginations of
      the surface are also less extensive than on the ventral side of the body.

PMID- 11316472
TI  - Experimental Oesophagostomum bifurcum in monkeys.
AB  - OESOPHAGOSTOMUM BIFURCUM: larvae, cultured from human stools collected in
      northern Ghana, were used to establish experimental infections in monkeys. A
      patent infection was established in a rhesus monkey (Macaca mulatta) and this
      infection was used to generate larvae to inoculate additional monkeys. In all, 17
      animals were inoculated. Thirteen of 15 animals developed antibodies to the
      infection between 19 and 62 days post inoculation (PI); two animals had a
      positive response before inoculation. Four of ten animals developed patent
      infections between 88 and 134 days and passed eggs in the faeces. Egg shedding
      was consistent in only one animal, but at low levels of one or two eggs per 2 mg
      direct smear, and extended over a 400 day period. In the other three animals, egg
      shedding was sporadic and of only 2-4 weeks duration. In seven animals necropsied
      between 19 and 22 days PI, one to 17 early fourth-stage larvae were recovered
      from nodules in the bowel wall; in an eighth animal examined at 314 days, six
      immature adult worms (early fifth stage) were recovered from nodules in the bowel
      wall. The morphological features and growth of these recovered larvae are
      described. Three animals were inoculated with larvae that had been dried for one
      week at 28 degrees C; two animals began shedding eggs at 128 and 134 days PI,
      respectively. The present results suggest that the parasite obtained from humans
      is poorly adapted to lower primate hosts, and supports the concept that
      Oesophagostomum bifurcum found in humans and monkeys in the same geographical
      region of northern Ghana and Togo are distinct and that the infections in humans
      are not likely to represent zoonotic infections acquired from monkeys.

PMID- 11316473
TI  - Purification and partial characterization of proteinase activity in eggs of
      Dicrocoelium dendriticum.
AB  - A preliminary purification has been carried out by continuous elution
      electrophoresis of a 49.5 kDa protease of crude extracts from Dicrocoelium
      dendriticum eggs. The enzyme showed a high capacity to degrade the collagen
      derivative azocoll at acidic pH. Although it is necessary to carry out further
      experiments to confirm any physiological role, this protease could be implicated
      in penetration mechanisms.

PMID- 11316474
TI  - Genetic diversity within the genus Trichinella as shown by cleavage fragment
      length polymorphism analysis.
AB  - The genetic diversity within the genus Trichinella was studied using cleavage
      fragment length polymorphism (CFLP) analysis. The CFLP method generates specific
      fingerprints based on single nucleotide mutations. By this method the amplified
      intergenic regions of the 5S rRNA genes of the eight different genotypes of
      Trichinella were analysed. The CFLP pattern of T. spiralis was completely
      different compared with the sylvatic species T. britovi, T. nativa, T. nelsoni,
      and the genotypes Trichinella T5, Trichinella T6 and Trichinella T8. The T.
      pseudospiralis intergenic region can be differentiated by size from the other
      species of Trichinella.

PMID- 11316475
TI  - Parasiticidal effects of peroxynitrite on ovine liver flukes in vitro.
AB  - Peroxynitrite (ONOO-) is a cytotoxic anion, produced by interaction between
      nitric oxide and superoxide in vivo in some inflammatory cells. This study
      investigated its effects on Fasciola hepatica and Dicrocoelium dendriticum
      isolated from ovine livers and kept in bile at room temperature. Peroxynitrite
      was synthesized using a quenched flow reactor and assayed spectrophotometrically.
      It was applied at different concentrations (10(-3.5) to 10(-2.3 M)) to the flukes
      kept in bile. The viability of the peroxynitrite-treated flukes was compared with
      a control group (n=5-7 per group). Control F. hepatica and D. dendriticum lived
      for 226+/-11and 208+/-14min, respectively. Life times were decreased by
      peroxynitrite at all concentrations used (P<0.001). At the highest concentration
      of peroxynitrite, F. hepatica and D. dendriticum lived only for 6.1+/-0.4 and
      4.1+/-4.1+/-0.2min, respectively. Correlation between peroxynitrite concentration
      and parasite viability was significant in the case of F. hepatica (r= -0.842; P=
      0.0035). A single application of peroxynitrite can decrease the life span of
      ovine liver flukes. A failure in the activation of hepatic macrophages in
      infected animals may lead to a decreased production of free radicals and, thus,
      peroxynitrite. Such a failure is likely to deprive the body of a defence tool
      against multicellular parasites.

PMID- 11316476
TI  - Effects of a diet deficient in the B complex vitamins on infectivity, growth and
      distribution of Echinostoma caproni in ICR mice.
AB  - The effects of a diet deficient in the B vitamins on infectivity, growth, and
      distribution of Echinostoma caproni in ICR mice were studied. The vitamin
      deficient diet (experimental) was isocaloric to the control diet but lacked the B
      vitamins. Thirty-six female, 6- to 8-week-old ICR mice were each infected with 25
      metacercarial cysts. From the day of infection to the day of necropsy, 18 mice
      were fed the experimental diet and the remaining mice received the control diet.
      Equal numbers of experimental and control mice were necropsied at 2, 3 and 4
      weeks postinfection (p.i.). Mice on the experimental diet showed a significant
      loss in body weight between 2 and 4 weeks p.i. There was no significant
      difference in worm recovery at 2 to 4 weeks p.i. from mice on either diet. Worms
      from hosts on the experimental diet were more dispersed and located more
      posteriad in the small intestine than those from mice on the control diet. Worm
      dry weight was significantly less in hosts on the experimental diet at all weeks
      p.i. compared with that of hosts on the control diet. The body area of worms on
      the experimental diet was significantly less at 2 and 3 weeks p.i. than that of
      worms on the control diet. An isocaloric diet deficient in the B vitamins had a
      detrimental effect on the growth of E. caproni in ICR mice.

PMID- 11316477
TI  - Redescription of Steinernema longicaudum Shen & Wang (Nematoda:
      Steinernematidae); geographic distribution and phenotypic variation between
      allopatric populations.
AB  - Steinernema longicaudum Shen & Wang is redescribed based on a comparative
      morphological study of specimens from the type isolate from China, and two other
      isolates recovered from Korea and the USA. For the first and second generation
      female, the location of the vulva, shape of the vulval lips, and shape and length
      of the tail were newly observed diagnostic characters. A more detailed
      description of the morphology of the male spicules and gubernaculum, and the
      arrangement of the genital papillae is included. A description, based on scanning
      electron microscopy observations, of the lateral field pattern of the third-stage
      infective juveniles is also provided. Additionally, restriction fragment length
      polymorphism profiles based on the internal transcribed spacer region, and cross
      breeding tests supplement the description of this species.

PMID- 11316478
TI  - Seasonal population dynamics of Neoechinorhynchus qinghaiensis in the carp,
      Gymnocypris przewalskii przewalskii, from Qinghai Lake, China.
AB  - Studies on the seasonal population dynamics of Neoechinorhynchus qinghaiensis
      (Acanthocephala: Neoechinorhynchidae) in its fish host Gymnocypris przewalskii
      przewalskii in the Qinghai Lake, China, were carried out with samples taken in
      May 1991, August 1992, November 1992 and February 1993. Prevalences were higher
      than 44% in all seasons. The mean intensity of infection was above 124 worms per
      fish. The maximum intensity of worms recovered from a single fish was 1402 in the
      autumn of 1992. Differences in the mean abundance, mean intensity and prevalence
      are not statistically significant relative to season and this is likely to be
      related to the stable temperatures recorded at the bottom of Qinghai Lake. Over
      dispersed distributions of N. qinghaiensis in the host population, due to
      heterogeneity and feeding habits, were observed in all seasons. The size
      composition of both sexes of N. qinghaiensis showed males to be less than 3.5 mm
      and females between 0.5 and 4.25 mm, with the main recruitment phase in the worm
      populations occurring in the autumn, extending through winter and spring with the
      lowest recruitment occurring in the summer. The maturation and copulation of
      worms were mainly focused in the summer season. The sex ratio of female to male
      was both high in winter (1.51:1) and spring (1.48:1). The higher proportion of
      females and the change in the worm sex ratio in winter can be attributed to the
      reduced longevity of male worms. As immature male worms exhibit a higher
      proportion of the worm population than females in all seasons, further studies
      are needed to determine if such a situation compensates for the shorter life span
      of males.

PMID- 11316480
TI  - Fruits, foliage and the evolution of primate colour vision.
AB  - Primates are apparently unique amongst the mammals in possessing trichromatic
      colour vision. However, not all primates are trichromatic. Amongst the haplorhine
      (higher) primates, the catarrhines possess uniformly trichromatic colour vision,
      whereas most of the platyrrhine species exhibit polymorphic colour vision, with a
      variety of dichromatic and trichromatic phenotypes within the population. It has
      been suggested that trichromacy in primates and the reflectance functions of
      certain tropical fruits are aspects of a coevolved seed-dispersal system: primate
      colour vision has been shaped by the need to find coloured fruits amongst
      foliage, and the fruits themselves have evolved to be salient to primates and so
      secure dissemination of their seeds. We review the evidence for and against this
      hypothesis and we report an empirical test: we show that the spectral positioning
      of the cone pigments found in trichromatic South American primates is well
      matched to the task of detecting fruits against a background of leaves. We
      further report that particular trichromatic platyrrhine phenotypes may be better
      suited than others to foraging for particular fruits under particular conditions
      of illumination; and we discuss possible explanations for the maintenance of
      polymorphic colour vision amongst the platyrrhines.

PMID- 11316481
TI  - Why we see things the way we do: evidence for a wholly empirical strategy of
      vision.
AB  - Many otherwise puzzling aspects of the way we see brightness, colour, orientation
      and motion can be understood in wholly empirical terms. The evidence reviewed
      here leads to the conclusion that visual percepts are based on patterns of reflex
      neural activity shaped entirely by the past success (or failure) of visually
      guided behaviour in response to the same or a similar retinal stimulus. As a
      result, the images we see accord with what the sources of the stimuli have
      typically turned out to be, rather than with the physical properties of the
      relevant objects. If vision does indeed depend upon this operational strategy to
      generate optimally useful perceptions of inevitably ambiguous stimuli, then the
      underlying neurobiological processes will eventually need to be understood within
      this conceptual framework.

PMID- 11316482
TI  - Geometric visual hallucinations, Euclidean symmetry and the functional
      architecture of striate cortex.
AB  - This paper is concerned with a striking visual experience: that of seeing
      geometric visual hallucinations. Hallucinatory images were classified by Kluver
      into four groups called form constants comprising (i) gratings, lattices,
      fretworks, filigrees, honeycombs and chequer-boards, (ii) cobwebs, (iii) tunnels,
      funnels, alleys, cones and vessels, and (iv) spirals. This paper describes a
      mathematical investigation of their origin based on the assumption that the
      patterns of connection between retina and striate cortex (henceforth referred to
      as V1)-the retinocortical map-and of neuronal circuits in V1, both local and
      lateral, determine their geometry. In the first part of the paper we show that
      form constants, when viewed in V1 coordinates, essentially correspond to
      combinations of plane waves, the wavelengths of which are integral multiples of
      the width of a human Hubel-Wiesel hypercolumn, ca. 1.33-2 mm. We next introduce a
      mathematical description of the large-scale dynamics of V1 in terms of the
      continuum limit of a lattice of interconnected hypercolumns, each of which itself
      comprises a number of interconnected iso-orientation columns. We then show that
      the patterns of interconnection in V1 exhibit a very interesting symmetry, i.e.
      they are invariant under the action of the planar Euclidean group E(2)-the group
      of rigid motions in the plane-rotations, reflections and translations. What is
      novel is that the lateral connectivity of V1 is such that a new group action is
      needed to represent its properties: by virtue of its anisotropy it is invariant
      with respect to certain shifts and twists of the plane. It is this shift-twist
      invariance that generates new representations of E(2). Assuming that the strength
      of lateral connections is weak compared with that of local connections, we next
      calculate the eigenvalues and eigenfunctions of the cortical dynamics, using
      Rayleigh-Schrodinger perturbation theory. The result is that in the absence of
      lateral connections, the eigenfunctions are degenerate, comprising both even and
      odd combinations of sinusoids in straight phi, the cortical label for orientation
      preference, and plane waves in r, the cortical position coordinate. 'Switching
      on' the lateral interactions breaks the degeneracy and either even or else odd
      eigenfunctions are selected. These results can be shown to follow directly from
      the Euclidean symmetry we have imposed. In the second part of the paper we study
      the nature of various even and odd combinations of eigenfunctions or planforms,
      the symmetries of which are such that they remain invariant under the particular
      action of E(2) we have imposed. These symmetries correspond to certain subgroups
      of E(2), the so-called axial subgroups. Axial subgroups are important in that the
      equivariant branching lemma indicates that when a symmetrical dynamical system
      becomes unstable, new solutions emerge which have symmetries corresponding to the
      axial subgroups of the underlying symmetry group. This is precisely the case
      studied in this paper. Thus we study the various planforms that emerge when our
      model V1 dynamics become unstable under the presumed action of hallucinogens or
      flickering lights. We show that the planforms correspond to the axial subgroups
      of E(2), under the shift-twist action. We then compute what such planforms would
      look like in the visual field, given an extension of the retinocortical map to
      include its action on local edges and contours. What is most interesting is that,
      given our interpretation of the correspondence between V1 planforms and perceived
      patterns, the set of planforms generates representatives of all the form
      constants. It is also noteworthy that the planforms derived from our continuum
      model naturally divide V1 into what are called linear regions, in which the
      pattern has a near constant orientation, reminiscent of the iso-orientation
      patches constructed via optical imaging. The boundaries of such regions form
      fractures whose points of intersection correspond to the well-known 'pinwheels'.
      To complete the study we then investigate the stability of the planforms, using
      methods of nonlinear stability analysis, including Liapunov-Schmidt reduction and
      Poincare-Lindstedt perturbation theory. We find a close correspondence between
      stable planforms and form constants. The results are sensitive to the detailed
      specification of the lateral connectivity and suggest an interesting possibility,
      that the cortical mechanisms by which geometric visual hallucinations are
      generated, if sited mainly in V1, are closely related to those involved in the
      processing of edges and contours.

PMID- 11316483
TI  - Quantitative aspects of metabolic organization: a discussion of concepts.
AB  - Metabolic organization of individual organisms follows simple quantitative rules
      that can be understood from basic physical chemical principles. Dynamic energy
      budget (DEB) theory identifies these rules, which quantify how individuals
      acquire and use energy and nutrients. The theory provides constraints on the
      metabolic organization of subcellular processes. Together with rules for
      interaction between individuals, it also provides a basis to understand
      population and ecosystem dynamics. The theory, therefore, links various levels of
      biological organization. It applies to all species of organisms and offers
      explanations for body-size scaling relationships of natural history parameters
      that are otherwise difficult to understand. A considerable number of popular
      empirical models turn out to be special cases of the DEB model, or very close
      numerical approximations. Strong and weak homeostasis and the partitionability of
      reserve kinetics are cornerstones of the theory and essential for understanding
      the evolution of metabolic organization.

PMID- 11316484
TI  - Large-scale heterogeneity of the fossil record: implications for Phanerozoic
      biodiversity studies.
AB  - Patterns of origination, extinction and standing diversity through time have been
      inferred from tallies of taxa preserved in the fossil record. This approach
      assumes that sampling of the fossil record is effectively uniform over time.
      Although recent evidence suggests that our sampling of the available rock record
      has indeed been very thorough and effective, there is also overwhelming evidence
      that the rock record available for sampling is itself distorted by major
      systematic biases. Data on rock outcrop area compiled for post-Palaeozoic
      sediments from Western Europe at stage level are presented. These show a strongly
      cyclical pattern corresponding to first- and second-order sequence
      stratigraphical depositional cycles. Standing diversity increases over time and,
      at the coarsest scale, is decoupled from surface outcrop area. This increasing
      trend can therefore be considered a real pattern. Changes in standing diversity
      and origination rates over time-scales measured in tens of millions of years,
      however, are strongly correlated with surface outcrop area. Extinction peaks
      conform to a random-walk model, but larger peaks occur at just two positions with
      respect to second-order stratigraphical sequences, towards the culmination of
      stacked transgressive system tracts and close to system bases, precisely the
      positions where taxonomic last occurrences are predicted to cluster under a
      random distribution model. Many of the taxonomic patterns that have been
      described from the fossil record conform to a species-area effect. Whether this
      arises primarily from sampling bias, or from changing surface area of marine
      shelf seas through time and its effect on biodiversity, remains problematic.

PMID- 11316485
TI  - Genetic and environmental risks for specific language impairment in children.
AB  - Specific language impairment (SLI) is the term used to refer to unexplained
      difficulties in language acquisition in children. Over the past decade, there has
      been rapid growth of evidence indicating that genes play an important part in the
      aetiology of SLI. However, further progress in elucidating the role of genes in
      causing SLI is limited by our lack of understanding of the phenotype. Studies to
      date have been hampered by the fact that we do not know whether SLI should be
      treated as a discrete disorder or a continuous variable, let alone which measures
      should be used to identify cases, or how many subtypes there are. Recent research
      suggests that theoretically motivated measures of underlying processes may be
      better than conventional clinical diagnoses for identifying aetiologically
      distinct types of language impairment. There has been a tendency for researchers
      to embrace parsimony and look for a single cause of SLI-or in any event, to
      identify different subtypes, each with a different single cause. Research is
      reviewed that suggests that may not be a fruitful approach to SLI, and that an
      approach in terms of multiple risk and protective factors, which is widely
      adopted in medicine, is more realistic.

PMID- 11316486
TI  - The neurobiology and evolution of cannabinoid signalling.
AB  - The plant Cannabis sativa has been used by humans for thousands of years because
      of its psychoactivity. The major psychoactive ingredient of cannabis is Delta(9)
      tetrahydrocannabinol, which exerts effects in the brain by binding to a G-protein
      coupled receptor known as the CB1 cannabinoid receptor. The discovery of this
      receptor indicated that endogenous cannabinoids may occur in the brain, which act
      as physiological ligands for CB1. Two putative endocannabinoid ligands,
      arachidonylethanolamide ('anandamide') and 2-arachidonylglycerol, have been
      identified, giving rise to the concept of a cannabinoid signalling system. Little
      is known about how or where these compounds are synthesized in the brain and how
      this relates to CB1 expression. However, detailed neuroanatomical and
      electrophysiological analysis of mammalian nervous systems has revealed that the
      CB1 receptor is targeted to the presynaptic terminals of neurons where it acts to
      inhibit release of 'classical' neurotransmitters. Moreover, an enzyme that
      inactivates endocannabinoids, fatty acid amide hydrolase, appears to be
      preferentially targeted to the somatodendritic compartment of neurons that are
      postsynaptic to CB1-expressing axon terminals. Based on these findings, we
      present here a model of cannabinoid signalling in which anandamide is synthesized
      by postsynaptic cells and acts as a retrograde messenger molecule to modulate
      neurotransmitter release from presynaptic terminals. Using this model as a
      framework, we discuss the role of cannabinoid signalling in different regions of
      the nervous system in relation to the characteristic physiological actions of
      cannabinoids in mammals, which include effects on movement, memory, pain and
      smooth muscle contractility. The discovery of the cannabinoid signalling system
      in mammals has prompted investigation of the occurrence of this pathway in non
      mammalian animals. Here we review the evidence for the existence of cannabinoid
      receptors in non-mammalian vertebrates and invertebrates and discuss the
      evolution of the cannabinoid signalling system. Genes encoding orthologues of the
      mammalian CB1 receptor have been identified in a fish, an amphibian and a bird,
      indicating that CB1 receptors may occur throughout the vertebrates.
      Pharmacological actions of cannabinoids and specific binding sites for
      cannabinoids have been reported in several invertebrate species, but the
      molecular basis for these effects is not known. Importantly, however, the genomes
      of the protostomian invertebrates Drosophila melanogaster and Caenorhabditis
      elegans do not contain CB1 orthologues, indicating that CB1-like cannabinoid
      receptors may have evolved after the divergence of deuterostomes (e.g.
      vertebrates and echinoderms) and protostomes. Phylogenetic analysis of the
      relationship of vertebrate CB1 receptors with other G-protein-coupled receptors
      reveals that the paralogues that appear to share the most recent common
      evolutionary origin with CB1 are lysophospholipid receptors, melanocortin
      receptors and adenosine receptors. Interestingly, as with CB1, each of these
      receptor types does not appear to have Drosophila orthologues, indicating that
      this group of receptors may not occur in protostomian invertebrates. We conclude
      that the cannabinoid signalling system may be quite restricted in its
      phylogenetic distribution, probably occurring only in the deuterostomian clade of
      the animal kingdom and possibly only in vertebrates.

PMID- 11316487
TI  - Transport of bile acids in hepatic and non-hepatic tissues.
AB  - Bile acids are steroidal amphipathic molecules derived from the catabolism of
      cholesterol. They modulate bile flow and lipid secretion, are essential for the
      absorption of dietary fats and vitamins, and have been implicated in the
      regulation of all the key enzymes involved in cholesterol homeostasis. Bile acids
      recirculate through the liver, bile ducts, small intestine and portal vein to
      form an enterohepatic circuit. They exist as anions at physiological pH and,
      consequently, require a carrier for transport across the membranes of the
      enterohepatic tissues. Individual bile acid carriers have now been cloned from
      several species. Na+-dependent transporters that mediate uptake into hepatocytes
      and reabsorption from the intestine and biliary epithelium and an ATP-dependent
      transporter that pumps bile acids into bile comprise the classes of transporter
      that are specific for bile acids. In addition, at least four human and five rat
      genes that code for Na+-independent organic anion carriers with broad multi
      substrate specificities that include bile acids have been discovered. Studies
      concerning the regulation of these carriers have permitted identification of
      molecular signals that dictate eventual changes in the uptake or excretion of
      bile acids, which in turn have profound physiological implications. This overview
      summarizes and compares all known bile acid transporters and highlights findings
      that have identified diseases linked to molecular defects in these carriers.
      Recent advances that have fostered a more complete appreciation for the elaborate
      disposition of bile acids in humans are emphasized.

PMID- 11316488
TI  - Lift-based paddling in diving grebe.
AB  - To examine the hydrodynamic propulsion mechanism of a diving great crested grebe
      (Podiceps cristatus), the three-dimensional kinematics was determined by digital
      analysis of sequential video images of dorsal and lateral views. During the
      acceleration phase of this foot-propelled bird, the feet move through an arc in a
      plane nearly normal to the bird's line of motion through the water, i.e. the toes
      move dorsally and medially but not caudally relative to the water. The kinematics
      of the grebe's lobed feet is different from that in anseriforms, whose feet move
      in a plane mostly parallel to the bird's line of progress through the water. Our
      results suggest that the foot-propelled locomotor mechanism of grebes is based
      primarily on a lift-producing leg and foot stroke, in contrast to the drag-based
      locomotion assumed previously. We suggest that the lift-based paddling of grebes
      considerably increases both maximum swimming speed and energetic efficiency over
      drag-based propulsion. Furthermore, the results implicate a new interpretation of
      the functional morphology of these birds, with the toes serving as a self
      stabilizing multi-slotted hydrofoil during the power phase.

PMID- 11316489
TI  - The process of cell adhesion among dissociated single cells of Hydra:
      morphological observations.
AB  - Ultrastructural observations were made on the initial adhesion process at the
      adherent region of Hydra endodermal cell pairs brought into contact (following
      dissociation) using a three-dimensional laser manipulator. Total contact length
      across the diameter of the adherent region decreased during the period 10-60 min
      after initial adhesion. However, the mean numbers of closest (<4 nm) and medium
      (5-25 nm) separation distances between membranes (thought to be important in
      total cell adhesion) were not significantly different. These data indicate that
      adherent cell pairs maintain a constant adhesiveness during the first 60 min of
      the adhesion process, despite membrane rearrangements. The relative length of
      each separation distance in adherent cell pairs approached that reported
      previously for intact Hydra. The sums of lengths in both the closest and medium
      categories (as a proportion of total contact length) increased because the length
      of cleavages (distances >25 nm) decreased significantly during the same time
      period. These results suggest that adherent cell pairs undergo rapid, active
      membrane changes in the adherent region, which might be associated with cell
      sorting. The possible significance of these changes for active rearrangement are
      discussed.

PMID- 11316490
TI  - Sarcomere number regulation maintained after immobilization in desmin-null mouse
      skeletal muscle.
AB  - The serial sarcomere number of skeletal muscle changes in response to chronic
      length perturbation. The role of the intermediate filament desmin in regulating
      these changes was investigated by comparing the architectural adaptations of the
      tibialis anterior, extensor digitorum longus (EDL) and soleus from wild-type mice
      with those of homozygous desmin knockout mice after hindlimb immobilization.
      After 28 days, serial sarcomere number increased significantly in the lengthened
      wild-type tibialis anterior (by approximately 9%) and EDL (by approximately 17%).
      Surprisingly, muscles from desmin knockout mice also experienced significant
      serial remodeling, with the serial sarcomere number of the tibialis anterior
      increasing by approximately 10% and that of the EDL by approximately 27%. A
      consistent result was observed in the shortened soleus: a significant decrease in
      sarcomere number was observed in the muscles from both wild-type (approximately
      26%) and knockout (approximately 12%) mice. Thus, although desmin is not
      essential for sarcomerogenesis or sarcomere subtraction in mouse hindlimb
      muscles, the results do suggest subtle differences in the nature of sarcomere
      number adaptation. We speculate that desmin may play a role in regulating the
      optimal arrangement of sarcomeres within the muscle or in sensing the magnitude
      of the immobilization effect itself.

PMID- 11316491
TI  - Juvenile coho salmon locomotion and mosaic muscle are modified by 3',3',5'-tri
      iodo-L-thyronine (T3).
AB  - Studies of maximum aerobic swimming performance in smolting juvenile salmonids
      indicate that these animals may be aerobically compromised during downstream
      migration. To test our hypothesis that hyperthyroid status contributes to
      decreased swimming performance through modification of muscle contractility in
      juvenile (112 mm mean total length) coho salmon (Oncorhynchus kisutch), we
      measured swimming performance and isolated muscle bundle contractility of fish
      implanted with 3',3',5'-tri-iodo-l-thyronine (T3) pellets, of fish implanted with
      sham pellets and of fish with no pellet implantation (control group). After 3
      weeks (N=12-13), critical swimming speeds (maximum aerobic swimming speed or
      U(crit)) were measured. Muscle bundles (N=15-16) were dissected from the hypaxial
      musculature and stimulated to measure the force and velocity of an isometric
      twitch and tetani. T3-treated fish demonstrated visible morphological changes
      associated with smoltification. Mean values of U(crit) were significantly
      decreased and the prolonged contraction (tetani) and twitch rates of contraction,
      relaxation and maximum force were significantly increased by T3 treatment
      compared with both the sham and control fish. Hematocrit, body mass and body
      length were not significantly affected by T3 treatment. In conclusion, we suggest
      that the reported decrease in U(crit) during salmonid smoltification may be
      mediated by endogenous T3-induced contractile modification of mosaic muscle
      fibers.

PMID- 11316492
TI  - Nitric oxide modulates cardiac performance in the heart of Anguilla anguilla.
AB  - Nothing is known about the effects of nitric oxide (NO) on cardiac performance in
      fish. Using an in vitro working heart preparation that generates physiological
      values of output pressure, cardiac output and ventricular work and power, we
      assessed the effects of NO on the cardiac performance of the eel Anguilla
      anguilla. We examined basal cardiac performance (at constant preload, afterload
      and heart rate), the effects of cholinergic stimulation and the Frank-Starling
      response (preload-induced increases in cardiac output at constant afterload and
      heart rate). The NO synthase (NOS) inhibitors NG-monomethyl-L-arginine (L-NMMA)
      and L-N5(1-iminoethyl)ornithine (L-NIO), the guanylate cyclase inhibitor 1H
      (1,2,4)oxadiazolo-(4,3-a)quinoxalin-1-one (ODQ) and Triton X-100, a detergent
      that damages the endocardial endothelium, all increased stroke volume (VS) and
      stroke work (WS). In contrast, the endogenous NOS substrate L-arginine, tested
      before and after treatment with haemoglobin, the NO donor 3
      morpholinosydnonimine, tested with and without the superoxide scavenger
      superoxide dismutase, and the stable cGMP analogue 8-bromoguanosine 3',5'-cyclic
      monophosphate (8-Br-cGMP) decreased VS and WS. Acetylcholine chloride produced a
      biphasic effect. At nanomolar concentrations, in 34 % of the preparations, it
      induced a NO-cGMP-dependent positive inotropism that required the integrity of
      the endocardial endothelium. Pretreatment with Triton X-100 or with NO-cGMP
      pathway inhibitors (L-NMMA, L-NIO, NG-nitro-l-arginine methyl ester, Methylene
      Blue and ODQ) abolished the positive effect of acetylcholine. In contrast, at
      micromolar concentrations, acetylcholine produced a negative effect that involved
      neither the endocardial endothelium nor the NO-cGMP pathway. Pre-treatment with L
      arginine (10(-6 )mol x l(-1)) was without effect, whereas L-NIO (10(-5 )mol x l(
      1)) significantly reduced the Frank-Starling response. Taken together, these
      three experimental approaches provide evidence that NO modulates cardiac
      performance in the eel heart.

PMID- 11316493
TI  - A novel mechanism of body mass regulation.
AB  - While significant attention has been devoted to the identification of hormonal
      factors that control body mass, little attention has been paid to the role of
      mechanical loading on animal mass. Here, we provide evidence that intraperitoneal
      implantation of metabolically inert mass results in a compensatory reduction in
      tissue mass. Deer mice (Peromyscus maniculatus) were surgically implanted with
      weights of 1, 2 or 3 g. There was a resulting loss of tissue mass (total body
      mass minus implant mass) that was proportional to the mass of the implant. This
      reduction in tissue mass followed a reduction in food intake in animals with 3 g
      implants. Evaluation of body composition failed to identify any single component
      that contributed to the loss of tissue mass. Removal of implants led to a
      transient restoration of body mass to levels similar to the total body mass of
      those control animals in which the implant had not been removed. However, within
      12 days of implant removal, body mass again declined to the level seen before
      implant removal. These results suggest the existence of a set point that is
      sensitive to changes in the perception of mass and that is transduced via neural
      pathways.

PMID- 11316494
TI  - Three-dimensional kinematics of skeletal elements in avian prokinetic and
      rhynchokinetic skulls determined by Roentgen stereophotogrammetry.
AB  - Several different types of cranial kinesis are present within modern birds,
      enabling them to move (part of) the upper bill relative to the braincase. This
      movement of the upper bill results from movement of the quadrate and the
      pterygoid-palatine complex (PPC). The taxon Palaeognathae is characterised by a
      very distinct PPC and a special type of cranial kinesis (central kinesis) that is
      very different from that found in the Neognathae. This has led some authors to
      hypothesise that there is a functional relationship between the morphology of the
      PPC and the type of cranial kinesis. This hypothesis is tested here by analysing
      the movement pattern of both the upper bill and the PPC in birds with three
      different types of cranial kinesis: prokinesis, distal rhynchokinesis and central
      rhynchokinesis. Movement patterns were determined using a Roentgen
      stereophotogrammetry method, which made it possible to detect very small
      displacements (0.5 mm) of bony elements in three dimensions, while the jaw
      muscles and ligaments remained intact. We found that in all types of kinesis
      investigated the movements of the quadrate, jugal bars and PPC are similar.
      Movement of the quadrate is transferred to the upper beak by the jugal bar and
      the PPC, which moves almost exclusively forwards and backwards, thereby elevating
      or depressing the upper bill. The differences between the types of kinesis lie
      only in the position of the point of rotation. These findings indicate that there
      is no correlation between the specific morphology of the PPC and the type of
      cranial kinesis. Several other factors, including the external forces applied
      during food acquisition, may influence the morphology of the PPC. Differences in
      PPC morphology therefore appear to be the result of different functional demands
      acting on the system simultaneously but with different strengths, depending on
      the species.

PMID- 11316495
TI  - Dynamics of mallard (Anas platyrynchos) gastrocnemius function during swimming
      versus terrestrial locomotion.
AB  - This study investigates how the contractile function of a muscle may be modulated
      to accommodate changes in locomotor mode and differences in the physical
      environment. In vivo recordings of lateral gastrocnemius (LG) activation, force
      development (measured using tendon buckle transducers) and length change
      (measured using sonomicrometry) were obtained from mallard ducks (Anas
      platyrhynchos) as they swam at steady speeds in a water tank and walked or ran on
      land. LG force recordings were compared with combined lateral and medial
      gastrocnemius (MG) muscle-tendon force recordings obtained from the contralateral
      limb, allowing force development by the MG to be estimated relative to that of
      the LG. Although similar stresses were calculated to act in the LG and MG muscles
      during terrestrial locomotion (126 and 115 kPa, respectively), stresses were
      considerably greater in the LG compared with the MG during swimming (62 versus 34
      kPa, respectively). During both steady swimming and terrestrial locomotion, the
      LG developed force while shortening over a considerable range of its length
      (swimming 23.6 % versus terrestrial 37.4 %). Activation of the muscle occurred
      near the end of passive lengthening during the recovery stroke, just prior to
      muscle shortening. As a result, the muscle generated broad positive work loops
      during both locomotor modes. LG work during swimming (4.8 J x kg(-1)) averaged 37
      % of the work performed during terrestrial locomotion (13.1 J x kg(-1)),
      consistent with the twofold greater force and 58 % greater strain of the muscle
      during walking and running. Because limb cycle frequency was similar for the two
      locomotor modes (swimming 2.65 versus terrestrial 2.61 Hz), differences in power
      output (swimming 12.6 W x kg(-1 )versus terrestrial 32.4 W x kg(-1)) largely
      reflected difference in work per cycle. Tendon elastic energy savings was a small
      fraction (<5 %) of the work performed by the muscle, consistent with a fiber
      tendon design of these two muscles that favors muscle work to produce limb
      movement with little tendon strain. These results are consistent with a higher
      cost of terrestrial locomotion in ducks compared with other, more cursorial birds
      that may operate their muscles more economically and achieve greater tendon
      elastic savings.

PMID- 11316496
TI  - Plasticity of chemotaxis revealed by paired presentation of a chemoattractant and
      starvation in the nematode Caenorhabditis elegans.
AB  - While the basic functioning of the nervous system of Caenorhabditis elegans has
      been extensively studied, its behavioural plasticities have not been fully
      explored because of the limited availability of assay systems. We report here a
      simple form of chemotaxis plasticity in this organism: when worms are starved on
      plates that contain NaCl, their chemotaxis towards NaCl falls dramatically. This
      conditioning requires both the presence of NaCl and the absence of a bacterial
      food source, indicating that it is not merely adaptation or habituation, but that
      it is likely to be a form of associative learning. While chemotaxis towards
      volatile chemoattractants does not change significantly after conditioning with
      NaCl, chemotaxis towards other water-soluble attractants does decrease. This
      suggests that an altered response of a cell or a group of cells specifically
      involved in chemotaxis towards water-soluble chemoattractants is responsible for
      the behavioural alteration. The decrease in chemotaxis occurred slowly over 3-4 h
      of conditioning and returned quickly to the original level when either of the
      conditioning stimuli, NaCl or starvation, was removed. The application of
      serotonin partially blocked this reduction in chemotaxis, consistent with the
      proposed function of this neurotransmitter in food signalling. Using this assay,
      we have isolated three mutants with reduced plasticity. This assay system expands
      the opportunities for studying the molecular and cellular mechanisms of
      behavioural plasticity in C. elegans.

PMID- 11316497
TI  - Comparison of the efficiency of rat papillary muscles during afterloaded isotonic
      contractions and contractions with sinusoidal length changes.
AB  - The results of previous studies suggest that the maximum mechanical efficiency of
      rat papillary muscles is lower during a contraction protocol involving sinusoidal
      length changes than during one involving afterloaded isotonic contractions. The
      aim of this study was to compare directly the efficiency of isolated rat
      papillary muscle preparations in isotonic and sinusoidal contraction protocols.
      Experiments were performed in vitro (27 degrees C) using left ventricular
      papillary muscles from adult rats. Each preparation performed three contraction
      protocols: (i) low-frequency afterloaded isotonic contractions (10 twitches at
      0.2 Hz), (ii) sinusoidal length change contractions with phasic stimulation (40
      twitches at 2 Hz) and (iii) high-frequency afterloaded isotonic contractions (40
      twitches at 2 Hz). The first two protocols resembled those used in previous
      studies and the third combined the characteristics of the first two. The
      parameters for each protocol were adjusted to those that gave maximum efficiency.
      For the afterloaded isotonic protocols, the afterload was set to 0.3 of the
      maximum developed force. The sinusoidal length change protocol incorporated a
      cycle amplitude of +/-5% resting length and a stimulus phase of -10 degrees.
      Measurements of force output, muscle length change and muscle temperature change
      were used to calculate the work and heat produced during and after each protocol.
      Net mechanical efficiency was defined as the proportion of the energy (enthalpy)
      liberated by the muscle that appeared as work. The efficiency in the low
      frequency, isotonic contraction protocol was 21.1+/-1.4% (mean +/- s.e.m., N=6)
      and that in the sinusoidal protocol was 13.2+/-0.7%, consistent with previous
      results. This difference was not due to the higher frequency or greater number of
      twitches because efficiency in the high-frequency, isotonic protocol was 21.5+/
      1.0%. Although these results apparently confirm that efficiency is protocol
      dependent, additional experiments designed to measure work output unambiguously
      indicated that the method used to calculate work output in isotonic contractions
      overestimated actual work output. When net work output, which excludes work done
      by parallel elastic elements, rather than total work output was used to determine
      efficiency in afterloaded isotonic contractions, efficiency was similar to that
      for sinusoidal contractions. The maximum net mechanical efficiency of rat
      papillary muscles performing afterloaded isotonic or sinusoidal length change
      contractions was between 10 and 15%.

PMID- 11316498
TI  - The anisotropic Young's modulus of equine secondary osteones and interstitial
      bone determined by nanoindentation.
AB  - The equine radius is a useful subject for examining the adaptation of bone
      histology to loading because in life the anterior cortex is loaded almost
      entirely in tension, the posterior cortex in compression. The histology of the
      two cortices is correspondingly different, the osteones and the interstitial
      lamellae in the posterior cortex having a more transversely oriented fibre
      arrangement than those in the anterior cortex. Presumably as a result of this
      histological difference, the posterior cortex is stronger in compression than the
      anterior cortex; the anterior cortex is stronger in tension than the posterior
      cortex. We here use nanoindentation to examine how the Young's modulus of
      elasticity of secondary osteones and interstitial lamellae in the anterior and
      posterior cortices varied as a function of angle. The anterior osteones were
      stiffer than the posterior osteones when tested in the direction parallel to the
      bone's long axis, but became progressively relatively less stiff as the angle
      increased; at 90 degrees, they were less stiff than the posterior osteones.
      Although the interstitial lamellae were stiffer than their neighbouring osteones,
      the same relationship between anterior and posterior interstitial lamellae as a
      function of angle was found as for the osteones. The anisotropy of these Young's
      moduli determined by nanoindentation shows a close relationship with what was to
      be expected from the histological findings.

PMID- 11316499
TI  - A maxi Cl- channel in cultured pavement cells from the gills of the freshwater
      rainbow trout Oncorhynchus mykiss.
AB  - Primary cultures of pavement cells from the gills of a freshwater fish, the
      rainbow trout Oncorhynchus mykiss, have been studied for the first time using the
      patch-clamp technique. Gigaohm seals were obtained in approximately 95% of cells
      studied, and channel activity was evident in a high proportion (>90%). A large
      conductance Cl- channel was evident in 6 % of cell-attached and in 31% of inside
      out patches. Single-channel conductance in inside-out patches was 372 pS, and
      current/voltage relationships were linear over the range -60 to +60 mV. The
      channel was activated by patch excision, and activation was often associated with
      polarization of the patch. The mean number of channels per patch was 1.9, and
      there were several subconductance states. The relationship between channel
      activity (NP(o)) and voltage was in the form of an inverted U, and channel
      activity was highest between 0 and +20 mV. Large-conductance Cl- channels showed
      a progressive time-dependent reduction in current in response to sustained
      polarization to voltages outside the range -20 mV to +20 mV. Permeability ratios
      (P) of Cl- to other anions were P(HCO3)/P(Cl)=0.81, P(SO4)/P(Cl)=0.31 and
      P(isethionate)/P(Cl)=0.53. The channel was blocked by Zn2+, SITS, DIDS and
      diphenylamine carboxylate. This is the first description of a large-conductance
      Cl- channel in gill cells from freshwater or marine species. Possible functions
      of the channel are discussed.

PMID- 11316501
TI  - The application of ground force explains the energetic cost of running backward
      and forward.
AB  - We compared backward with forward running to test the idea that the application
      of ground force to support the weight of the body determines the energetic cost
      of running. We hypothesized that higher metabolic rates during backward versus
      forward running would be directly related to greater rates of ground force
      application and the volume of muscle activated to apply support forces to the
      ground. Four trained males ran backward and forward under steady-state conditions
      at eight treadmill speeds from 1.75 to 3.50 m x s(-1). Rates of oxygen uptake
      were measured to determine metabolic rates, and inverse periods of foot-ground
      contact (1/tc) were measured to estimate rates of ground force application. As
      expected, at all eight speeds, both metabolic rates and estimated rates of ground
      force application were greater for backward than for forward running. At the five
      slowest speeds, the differences in rates of ground force application were
      directly proportional to the differences in metabolic rates between modes (paired
      t-test, P<0.05), but at the three highest speeds, small but significant
      differences in proportionality were present in this relationship. At one of these
      three higher speeds (3.0 m x s(-1)), additional measurements to estimate muscle
      volumes were made using a non-invasive force plate/video technique. These
      measurements indicated that the volume of muscle active per unit of force applied
      to the ground was 10+/-3% greater when running backward than forward at this
      speed. The product of rates of ground force application and estimated muscle
      volumes predicted a difference in metabolic rate that was indistinguishable from
      the difference we measured (34+/-6% versus 35+/-6%; means +/- s.e.m., N=4). We
      conclude that metabolic rates during running are determined by rates of ground
      force application and the volume of muscle activated to apply support forces to
      the ground.

PMID- 11316500
TI  - The Drosophila melanogaster homologue of an insect calcitonin-like diuretic
      peptide stimulates V-ATPase activity in fruit fly Malpighian tubules.
AB  - The Drosophila melanogaster homologue of an insect calcitonin-like diuretic
      hormone was identified in a BLAST search of the Drosophila genome database. The
      predicted 31-residue amidated peptide (D. melanogaster DH31; Drome-DH31) was
      synthesised and tested for activity on fruit fly Malpighian tubules. It increases
      tubule secretion by approximately 35 % of the response obtained with a myokinin
      from the housefly Musca domestica (muscakinin; Musdo-K) and has an EC50 of 4.3
      nmol x l(-1). The diuretic activities of Drome-DH31 and Musdo-K were additive
      when tested at threshold and supra-maximal concentrations, which suggests that
      they target different transport processes. In support of this, Drome-DH31
      increased the rate of secretion by tubules held in bathing fluid with a reduced
      Cl- concentration, whereas Musdo-K did so only in the presence of Drome-DH31.
      Stimulation with Drome-DH31 increased the lumen-positive transepithelial
      potential in the main secretory segment of the tubule. This was attributed to
      activation of an apical electrogenic proton-translocating V-ATPase in principal
      cells, since it was associated with hyperpolarisation of the apical membrane
      potential and acidification of secreted urine by 0.25 pH units. Exogenous 8-bromo
      cyclic AMP and cyclic GMP increased tubule secretion to the same extent as Drome
      DH31 and, when tested together with the diuretic peptide, their activities were
      not additive. Stimulation with Drome-DH31 resulted in a dose-dependent increase
      in cyclic AMP production by tubules incubated in saline containing 0.5 mmol x l(
      1) 3-isobutyl-1-methylxanthine, whereas cyclic GMP production was unchanged.
      Taken together, the data are consistent with Drome-DH31 activating an apical
      membrane V-ATPase via cyclic AMP. Since the K+ concentration of the secreted
      urine was unchanged, it is likely that Drome-DH31 has an equal effect on K+ and
      Na+ entry across the basolateral membrane.

PMID- 11316502
TI  - The dynamics and scaling of force production during the tail-flip escape response
      of the California spiny lobster Panulirus interruptus.
AB  - The tail-flip escape behavior is a stereotypical motor pattern of decapod
      crustaceans in which swift adduction of the tail to the thorax causes the animal
      to rotate, move vertically into the water column and accelerate rapidly
      backwards. Previous predictions that a strong jet force is produced during the
      flip as the tail adducts to the body are not supported by our simultaneous
      measurements of force production (using a transducer) and the kinematics (using
      high-speed video) of tail-flipping by the California spiny lobster Panulirus
      interruptus. Maximum force production occurred when the tail was positioned
      approximately normal to the body. Resultant force values dropped to approximately
      15% of maximum during the last third of the flip and continued to decline as the
      tail closed against the body. In addition, maximum acceleration of the body of
      free-swimming animals occurs when the tail is positioned approximately normal to
      the body, and acceleration declines steadily to negative values as the tail
      continues to close. Thus, the tail appears to act largely as a paddle. Full
      flexion of the tail to the body probably increases the gliding distance by
      reducing drag and possibly by enhancing fluid circulation around the body.
      Morphological measurements indicate that Panulirus interruptus grows
      isometrically. However, measurements of tail-flip force production for
      individuals with a body mass (Mb) ranging from 69 to 412 g indicate that
      translational force scales as Mb0.83. This result suggests that force production
      scales at a rate greater than that predicted by the isometric scaling of muscle
      cross-sectional area (Mb2/3), which supports previously published data showing
      that the maximum accelerations of the tail and body of free-swimming animals are
      size-independent. Torque (tau) scaled as Mb1.29, which is similar to the
      hypothesized scaling relationship of Mb4/3. Given that tau is proportional to
      Mb1.29, one would predict rotational acceleration of the body (alpha) to decrease
      with increasing size as Mb(-0.37), which agrees with previously published
      kinematic data showing a decrease in alpha with increased Mb.

PMID- 11316503
TI  - Is "somatisation" a defense against the acknowledgment of psychiatric disorder?
AB  - OBJECTIVE: To determine whether experiencing physical symptoms is associated with
      a denial of psychological distress in individuals with probable psychiatric
      disorder. METHODS: A nested case-control study was performed using data from a
      national birth cohort study. All subjects who scored above threshold on a case
      finding questionnaire of psychiatric disorder were identified. Those who in a
      separate question endorsed the presence of psychiatric disorder ("acknowledgers")
      were compared with those who did not. RESULTS: Acknowledgers were more likely to
      be female, better educated and have more severe current and past psychiatric
      disorder. They were also more likely to report multiple physical symptoms, even
      when potential confounders and severity of psychiatric disorder were controlled.
      CONCLUSION: There is no evidence that experiencing multiple physical symptoms
      helps the individual deny the presence of psychiatric disorder.

PMID- 11316504
TI  - Alexithymia in patients with coronary heart disease.
AB  - OBJECTIVE: The aim of this study was to investigate factors associated with
      alexithymia in patients (n=153) with coronary heart disease (CHD) verified by
      coronary angiography. METHOD: Self-rated depression was assessed using 21-item
      Beck Depression Inventory (BDI) and other psychiatric symptoms with Symptom Check
      List-90 (SCL-90). Life satisfaction was assessed using a separate scale. The
      Structured Clinical Interview (SCID I and II) for DSM-III-R was used to identify
      mental disorders. Assessments took place 1 day before angiography. RESULTS:
      Twenty-one percent of CHD patients (n=32) were assessed as being alexithymic
      according to the Toronto Alexithymia Scale (TAS-20). Alexithymics were more often
      blue-collar workers, incapable of working, dissatisfied with life, and depressed
      than the other CHD patients. Occurrences of mental disorders were not associated
      with alexithymia. Logistic regression analysis revealed that factors
      independently associated with alexithymia were currently or previously being a
      blue-collar worker (adjusted odds ratio, AOR: 4.8), self-rated depression (AOR:
      3.2), and dissatisfaction with life (AOR: 2.9). CONCLUSION: In CHD patients
      alexithymia was unrelated to cardiovascular risk factors or exercise capacity but
      was related to self-rated depression and decreased life satisfaction. Alexithymia
      is associated with the enhanced psychosocial burden of suffering CHD. This
      patient group may need more individual support and attention than other CHD
      patients.

PMID- 11316505
TI  - The influence of health beliefs on the presentation and consultation outcome in
      patients with chemical sensitivities.
AB  - OBJECTIVE: This study was carried out to investigate the impact of the physical
      effects of a chemical exposure, health and chemical beliefs, and chemical
      sensitivities treatment preferences on the consultation outcome at a tertiary
      liaison clinic. METHOD: Eighty-five patients exposed to a range of chemicals were
      assessed at a joint medical toxicology and psychiatric clinic. Patient's beliefs
      about chemicals and health, chemical sensitivities and their treatment
      preferences were assessed using a 23-item questionnaire. RESULTS: Fifty-seven
      patients (69%) had suffered from a range of initial or delayed symptoms that were
      probably a clear physical consequence of the exposure (Group A), whereas 26
      patients (31%) had not (Group B). There were no significant differences found
      between groups A and B in terms of their diagnosis and their beliefs about
      health, food, chemicals and chemical sensitivities treatment preferences.
      However, patients in Group A were significantly more likely to report moderate to
      severe symptoms in comparison to Group B. Consultation outcome too did not differ
      between the two groups. The only predictors of consultation outcome were the
      patients' chemical sensitivities treatment preferences. Patients who at the
      outset thought that their treatment should comprise of complete avoidance to
      chemicals, regular monitoring and the use of alternative rather than conventional
      medicine were significantly less likely to achieve a favourable consultation
      outcome. Patients' chemical sensitivities treatment preferences were related to
      the more general beliefs on health, food and the harmful nature of chemicals and
      were not related to the chemical exposure variables. CONCLUSION: These findings
      suggest that addressing patients' treatment preferences and the general beliefs
      on chemicals, food and health may enhance outcome and perhaps ought to be the
      target for intervention in context of such a liaison clinic.

PMID- 11316506
TI  - Personality and physical symptoms in nonpsychiatric patients with functional
      gastrointestinal disorder.
AB  - OBJECTIVE: We investigated the relationship between personality and reported pain
      and somatic distress in patients with functional gastrointestinal disorder (FGD)
      without psychopathology. METHODS: Fifty-six patients and 55 controls completed
      Buss-Durkee Hostility Inventory (BDHI), NEO Personality Inventory (NEO-PI),
      Eysenck Personality Questionnaire (EPQ: N+L scales), and Giessener Physical
      Complaints Checklist (GBB). Patients also completed McGill Pain Questionnaire
      (MPQ) and Visual Analogue Scale (VAS) for abdominal pain and target symptom
      (abdominal distress). RESULTS: Patients displayed significantly higher levels of
      neuroticism and covert aggression than controls. Number of words chosen (NWC) to
      describe pain and sensory pain index (MPQ), but not pain intensity on VAS, were
      predicted by indirect aggression -- and less so by neuroticism -- in females and
      covert aggression in males (stepwise regression model). Patients reported far
      more extraintestinal somatic complaints than controls. CONCLUSION: Out of nine
      dimensions of hostility and five dimensions of personality, only neuroticism and
      concealed aggression are increased in FGD patients without psychiatric
      comorbidity compared with healthy controls. These personality traits influence
      pain reports and should be taken into account when evaluating and treating
      patients with FGD. Neuroticism and concealed aggression are most likely markers
      of vulnerability to FGD and not merely reflections of being chronic ill or
      explained by sample bias secondary to illness behavior.

PMID- 11316507
TI  - Alternative medicine in a sample of 655 community-dwelling elderly.
AB  - OBJECTIVE: Use and satisfaction with herbal/homeopathic remedies, acupuncture and
      relaxation techniques were examined in an Italian elderly population. METHODS:
      Data were collected as part of a survey on an elderly population, conducted in
      1996--1997 in the urban centre of Padua, Italy. A total of 1362 elderly received
      a letter inviting them to participate and to accept the visit of an interviewer
      at home. Of these, 212 were unable to do so for insurmountable reasons and 666
      gave consent to take part in the study with a response rate of 65%. Eleven
      participants were excluded from the study because cognitively impaired. RESULTS:
      Among the 655 respondents, overall use of at least one alternative medicine was
      29.5%. Herbs/phytotherapeutics (47%) and acupuncture (34%) were the most
      frequently cited therapies. The use of alternative medical practices seems rather
      widespread among the elderly population in Padua, especially among females with
      depressive symptoms, pain and discomfort, but not suffering from chronic somatic
      disease. A percentage of 3.7% of the sample used exclusively alternative
      medicines; those subjects seemed to be younger, less likely to be physically ill
      and to report functional disorders and chronic somatic disease. CONCLUSION:
      Alternative medicines seem to have a complementary role for the elderly with self
      perceived psychological symptomatology or disorders, particularly of depressive
      nature. They may constitute an attempt at self-treatment, probably concealing the
      difficulties encountered by the elderly subjects in seeking specialist advice for
      these problems.

PMID- 11316508
TI  - The effects of homeopathic belladonna 30CH in healthy volunteers -- a randomized,
      double-blind experiment.
AB  - OBJECTIVES: The practice of homeopathy rests on symptoms, which have been
      produced by medicinal substances in healthy volunteers, often applied at
      ultramolecular dilutions. It is unknown whether these symptom patterns are due to
      specific effects or chance fluctuation. METHODS: We tested the hypothesis that a
      homeopathic substance can bring about symptoms different from observation and
      placebo in a double-blind, placebo-controlled crossover design with baseline
      observation. RESULTS: 87 out of 118 healthy volunteers took both placebo and
      homeopathic belladonna 30CH in random sequence, after a 2-week observation
      period, and finished the 8-week trial. Apart from an insignificant tendency for
      subjects to report more symptoms with belladonna (mean number: 27.34), as
      compared to observation (24.26) or placebo (24.17), there was no indication that
      subjects reacted differently to homeopathy than to placebo or during baseline.
      CONCLUSION: There is no indication that belladonna 30CH produces symptoms
      different from placebo or from no intervention. Symptoms of a homeopathic
      pathogenetic trial (HPT) are most likely chance fluctuations.

PMID- 11316510
TI  - Regulations of opioid dependence by opioid receptor types.
AB  - Three major types of opioid receptors, designated mu, delta, and kappa, are
      widely expressed in the CNS. Development of selective receptor ligands and recent
      cloning of each receptor have contributed greatly to our increasing knowledge of
      the neuropharmacological profile of each opioid receptor type. It is of interest
      to note that they include noncompetitive and allosteric interactions among their
      types. This review focuses on the functional interaction among these opioid
      receptor types that contribute to opioid dependence. Various studies provide
      arguments to support substantial roles for mu-opioid receptors and the possible
      involvement of delta-opioid receptors in the development of physical and
      psychological dependence on morphine. Noradrenergic transmission originating in
      the locus coeruleus is most likely to play the primary causal role in the
      expression of physical dependence on morphine. In contrast, many studies have
      pointed to the mesolimbic dopaminergic pathway projecting from the ventral
      tegmental area to the nucleus accumbens as a critical site for the initiation of
      psychological dependence on opioids. It is noteworthy as the broad existence of
      opposing interactions between mu/delta- and kappa-receptors in the brain. The
      activation of kappa-receptors leads to the suppression of unpleasant mu/delta
      mediated side effects such as the rewarding effect. Considering the functional
      interaction among opioid receptor types, the co-administration of morphine-like
      compounds with kappa-receptor agonists may constitute a preferable and superior
      approach to the treatment of pain with fewer side effects.

PMID- 11316509
TI  - Psychiatric status, somatisation, and health care utilization of frequent
      attenders at the emergency department: a comparison with routine attenders.
AB  - Seventy-seven frequent attenders at an emergency department (ED) in an inner-city
      hospital in the UK (defined as seven or more visits in the previous 12 months)
      were compared with 182 patients who were attending the same department on a
      routine basis. Patients completed the Schedules for Clinical Assessment in
      Neuropsychiatry (SCAN) and the Short Form (SF)-36. Information was obtained on
      64% of the frequent attenders and 45% underwent a detailed psychiatric
      assessment. Of the frequent attenders, 45% had psychiatric disorder and 49% had
      some form of an alcohol-related disorder. Compared with routine attenders,
      frequent attenders reported lower health status, had more psychiatric disorder
      (odds ratio: OR=8.2, 95% confidence interval: CI=3.8--18.1), had more general
      hospital admissions (OR=19.9, 95% CI=8.3--47.8), more psychiatric admissions
      (OR=167.5, 95% CI=9.5--2959.0), and more GP visits (95% CI for difference=-10.2
      to -5.7). There was no evidence that frequent attenders had more somatisation
      than routine attenders. Specific treatment and management strategies need to be
      developed for this group of patients, although a substantial proportion may be
      difficult to engage in the treatment process.

PMID- 11316511
TI  - Antiretroviral therapeutic possibilities for human immunodeficiency
      virus/acquired immunodeficiency syndrome.
AB  - In human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS)
      illness, the reverse transcriptase and protease (PRT) enzymes of HIV are
      currently the targets of antiretroviral (ARV) therapy. Nucleoside analogues were
      the first group of ARV drugs that exerted antiviral activity in patients. More
      recently, PRT inhibitors have provided new approaches in the treatment of HIV
      infection and AIDS. Impressive clinical results have been obtained with
      combination therapies of three ARV drugs, including one PRT inhibitor. It is
      worth mentioning also that apart from these two main drug groups, there are many
      new compounds under development, including a vaccine(s) against HIV.

PMID- 11316512
TI  - Mitochondria: a target for myocardial protection.
AB  - The ischemic heart requires reperfusion using clinical interventions, such as
      coronary artery bypass graft surgery, in order to recover. Despite recent
      developments in myocardial protection techniques, reperfusion damage still
      occurs, and significant morbidity remains a problem. Therefore, the search
      continues for techniques that will limit myocardial damage and that will enhance
      recovery upon reperfusion. Mitochondria are known to be intimately involved in
      the processes that lead to cell death following reperfusion, in both necrotic and
      apoptotic forms of cell death, and so are potential targets for protective
      intervention. In this review, we consider several aspects of mitochondrial
      function that we believe to be possible targets for myocardial protection;
      namely, mitochondrial Ca(2+) transport, the permeability transition pore, and
      improved mitochondrial substrate supply. We discuss work by ourselves and others
      in these areas, and also consider the recently proposed role of mitochondrial ATP
      dependent K(+) channels in mediating myocardial protection by ischemic
      preconditioning. Finally, we describe use of cardioplegic solutions in the
      clinical setting, and discuss how improved understanding of the aspects of
      mitochondrial function summarised above may lead to better protective strategies
      in the future.

PMID- 11316513
TI  - Modulation of sarcoplasmic reticulum function: a new strategy in
      cardioprotection?
AB  - This article reviews the experimental evidence suggesting that cytosolic Ca(2+)
      overload plays a major role in the development of myocardial injury during
      ischemia-reperfusion and that Ca(2+) release from the sarcoplasmic reticulum (SR)
      is of crucial importance in the early phase of ischemia. It is suggested that
      interventions able to deplete the SR Ca(2+) pool and/or to reduce the rate of SR
      Ca(2+) release should be cardioprotective. This thesis is supported by the review
      of experimental studies in which modulators of the SR Ca(2+)-ATPase or SR Ca(2+)
      release channel (ryanodine receptor) have been used. In addition, the role of the
      SR in ischemic preconditioning and in some instances of toxic myocardial injury
      (particularly, anthraquinone-induced injury) is discussed.

PMID- 11316514
TI  - Pharmacologic therapy of persistent pulmonary hypertension of the newborn.
AB  - Persistent pulmonary hypertension of the newborn (PPHN) is a potentially life
      threatening condition characterized by a failure of pulmonary vascular resistance
      to decrease adequately during the transition to extrauterine life. Inhaled nitric
      oxide, a vasodilator that acts selectively on the pulmonary circulation, has
      revolutionized the treatment of this condition. However, inhaled nitric oxide has
      not proven effective in all patients, particularly those with congenital
      diaphragmatic hernias or meconium aspiration syndrome. Furthermore, large
      clinical trials of inhaled nitric oxide have failed to demonstrate significant
      differences in mortality between nitric oxide-treated and control infants with
      PPHN. Other therapeutic approaches to PPHN have been limited by a relative lack
      of specificity for the pulmonary circulation, and have received much less
      attention. Pharmacologic approaches, including pulmonary surfactants,
      prostacyclin, endothelin antagonists, Ca(2+)-channel blockers, magnesium sulfate,
      and tolazoline, have exhibited varying degrees of efficacy in lowering pulmonary
      vascular pressures in humans and/or animals. A number of these agents are also
      effective when used in combination. For example, phosphodiesterase inhibitors
      have been reported to act synergistically with inhaled nitric oxide. Surfactants
      also appear to be useful in PPHN, particularly in patients with congenital
      diaphragmatic hernia, when used in combination with other therapies. Surfactant
      lavage and other novel therapies may also be effective in combination therapy of
      meconium aspiration syndrome. Further studies should be directed at defining the
      optimal therapies in specific clinical settings. Validation of multiple
      therapeutic modalities for PPHN, including inhaled nitric oxide, will allow for
      rational, combined vasodilator strategies that are specific for the underlying
      pathophysiology in each patient.

PMID- 11316515
TI  - Anti-obesity drugs: a critical review of current therapies and future
      opportunities.
AB  - The last 25 years have seen a great increase in the incidence of obesity, both in
      the Western world and in developing third world countries. Despite the seeming
      inexorable progression of this disease, there have been limited advances in the
      pharmacotherapy of this condition. Of the newest introductions to the obesity
      drug portfolio, orlistat, which acts to prevent dietary fat absorption, and
      sibutramine, which seems to affect both arms of the energy balance equation, were
      the first new chemical entities to be introduced for the treatment of obesity in
      30 years. In this article, we review these and other agents available in various
      countries for the treatment of obesity. Perhaps more importantly, we have
      focussed on areas of potential productivity in the future. The huge recent
      increase in our knowledge in this area has largely stemmed from discovery
      research at the genomics level. Over the last 5 or so years, this impetus in
      obesity research has provided us with exciting new drug targets involved in the
      regulation of feeding behaviour and cellular mechanisms involved in energy
      expenditure. Compared with the last 25 years, the future offers more hope.

PMID- 11316516
TI  - Opioids and cardioprotection.
AB  - Opioid peptides and exogenous opioids such as morphine are known to exert
      important cardiovascular effects. However, until recently, it was not appreciated
      that activation of specific receptors results in a potent cardioprotective effect
      to reduce infarct size in experimental animals and to reduce cell death in
      isolated cardiomyocytes. In intact rat and rabbit hearts, nonselective opioid
      receptor antagonists such as naloxone and a selective delta1-opioid receptor
      antagonist, 7-benzylidenenaltrexone, have been shown to inhibit the
      cardioprotective effect of ischemic preconditioning, a phenomenon in which brief
      periods of ischemia protect the heart against a more prolonged period of
      ischemia. Selective delta(1) specific agonists such as 2-methyl-4a-alpha-(3
      hydroxyphenyl)-1,2,3,4,4a,5,12,12a-alpha-octahydroquinolino[2,3,3-g]isoquinoline
      have been shown to exert potent cardioprotective effects in intact animals and
      cardiac myocytes via activation of Gi/o proteins, protein kinase C, and
      ultimately, the mitochondrial KATP channel. These protective effects occur
      immediately following drug administration, and reappear 24-48 hr post treatment.
      Although further studies are needed to more clearly define the mechanisms by
      which opioids exert their cardioprotective effects, the data accumulated and
      summarized in this review suggest that this class of drugs may not only be useful
      in alleviating the pain associated with a myocardial infarction, but may also be
      simultaneously reducing the size of the ultimate infarct. Since many of these
      drugs are already clinically available, a long period of drug development may not
      be necessary before the use of these drugs reaches the patient with signs of
      myocardial ischemia.

PMID- 11316517
TI  - Diversity and specificity in the regulated endocytic membrane trafficking of G
      protein-coupled receptors.
AB  - Many G-protein-coupled receptors (GPCRs) are regulated by endocytosis.
      Pharmacological studies defining distinct processes of ligand-induced
      sequestration and down-regulation provided early evidence for significant
      complexity in the endocytic membrane trafficking of GPCRs. In this review, we
      discuss our present understanding of the diversity and specificity of GPCR
      endocytic membrane trafficking, focusing primarily on proteolytic down-regulation
      of GPCRs via delivery to lysosomes. We discuss evidence suggesting that certain
      GPCRs can be targeted selectively to lysosomes after endocytosis by the same
      membrane pathway that mediates the process of rapid sequestration, and we
      highlight recent progress in understanding a mechanism that controls the sorting
      of a specific GPCR between distinct membrane pathways after endocytosis by
      clathrin-coated pits.

PMID- 11316518
TI  - Serine/threonine kinases as molecular targets of antidepressants: implications
      for pharmacological treatment and pathophysiology of affective disorders.
AB  - It is currently a widely accepted opinion that adaptive, plastic changes in the
      molecular and cellular components of neuronal signaling systems correlate with
      the effects on mood and cognition observed after long-term treatment with
      antidepressant drugs. Protein phosphorylation represents a key step for most
      signaling systems, and it is involved in the regulation of virtually all cellular
      functions. Two serine/threonine kinases, Ca2+ /calmodulin-dependent protein
      kinase II and cyclic AMP-dependent protein kinase, have been shown to be
      activated in the brain following antidepressant treatment. The changes in kinase
      activity are mirrored by changes in the phosphorylation of selected protein
      substrates in subcellular compartments (presynaptic terminals and microtubules),
      which, in turn, may contribute to the modulation of synaptic transmission
      observed with antidepressants. The molecular consequences of protein kinase
      activation may account for some of the alterations in neural function induced by
      antidepressants, and may suggest novel possible strategies of pharmacological
      intervention.

PMID- 11316519
TI  - Natural and synthetic inhibitors of UDP-glucuronosyltransferase.
AB  - Glucuronidation is a major detoxification pathway in vertebrates. The reaction is
      catalyzed by a family of UDP-glucuronosyltransferases (UGTs) and involves
      conjugation of many endobiotic and xenobiotic substances with glucuronic acid,
      forming inactive water-soluble glucuronides. UGT prevents the accumulation of
      potentially toxic compounds and/or their subsequent bioactivation to more toxic
      intermediates, although biologically active glucuronides are also known.
      Impairment of UGTs may have important toxicological consequences. Substances
      found to inhibit or down-regulate UGT activity include endogenous compounds, a
      wide range of clinically used drugs, environmental contaminants, and natural
      toxic substances present in the diet. The development of selective, active-site
      directed UGT inhibitors greatly enables the study of various UGT isoenzymes. A
      promising approach offers the design of transition-state analogs of the
      glucuronidation reaction.

PMID- 11316520
TI  - Oxidative pathways in cardiovascular disease: roles, mechanisms, and therapeutic
      implications.
AB  - Despite some recent declines, cardiovascular disease (CVD) remains the major
      cause of death in the United States and worldwide. Most recent advances in the
      treatment of CVD states have been produced by inhibition of mechanisms involved
      in disease progress. Many studies conducted in the last decade have illustrated
      increased biological oxidative pathways during CVD in animals and humans. Thus,
      increased production of reactive oxygen species may be a unifying mechanism in
      CVD progression, and antioxidants may have therapeutic value in this setting. In
      this review we address the following questions: Do oxidative mechanisms play a
      role in CVD? Where do the oxidants come from? What are the relevant oxidative
      events? What are the therapeutic implications?

PMID- 11316521
TI  - Mode of action and mechanisms of resistance for antimalarial drugs.
AB  - Understanding the mode of action of and mechanism of resistance to drugs is
      central to optimising their use, and discovering new therapeutics with novel
      targets. We have limited understanding of how antimalarial drugs work and how
      resistance emerges. With few exceptions, antimalarial drugs in current use belong
      to a limited collection of chemical structures that act on a small number of
      partially characterised biochemical targets. Resistance has emerged to many of
      these compounds. The use of closely related compounds has promoted the spread of
      multidrug resistant parasites. This review intends to collate contemporary
      knowledge, and also to highlight conflicting views on unresolved issues.

PMID- 11316522
TI  - Tribute: Hans-Rudolph Muller.

PMID- 11316523
TI  - New lesions detected by intraoperative ultrasound during liver resection for
      hepatocellular carcinoma.
AB  - During liver resection for hepatocellular carcinoma (HCC), it is not uncommon for
      examinations by intraoperative ultrasound (IOUS) to detect small new lesions that
      were not found by preoperative examinations. Although a differential diagnosis is
      critical, it has not yet been established if IOUS is useful for this purpose with
      such small lesions. A total of 90 new lesions detected by IOUS in 79 liver
      resections were analysed. IOUS was performed on all of these cases and the
      features were recorded. The histologic characteristics of these 90 new lesions
      were checked by needle biopsy and their relations to the clinical data were
      analyzed. The IOUS pattern of the lesion was hypoechoic in 36 cases, hyperechoic
      in 49 and mosaic in 5. A total of 24 HCC lesions were detected and the incidences
      of malignancy for each type were 30.6%, 18.4% and 80.0%, respectively. Multiple
      regression analysis revealed that the IOUS features of the new lesions were the
      only significant factors in predicting the histology. IOUS should be mandatory in
      liver resection for HCC because it is useful for finding new lesions and might
      contribute to prediction of the histologic features.

PMID- 11316524
TI  - Ultrasonic characterization of maturation of fetal lung microstructure: an animal
      study.
AB  - Scattering parameters and histological properties of the ewe fetal lung
      microstructure were examined in vitro. Four groups of lamb fetuses were chosen at
      80, 100, 130 and 145 days of gestation (10 lambs in all). The acoustic parameters
      of the lung (backscatter coefficient, integrated backscatter coefficient and
      effective scatterer size), texture parameter of the lung (effective density of
      scatterers) and a relative lung/liver maturation parameter (the integrated
      spectral ratio) were measured at 19 degrees +/- 2 degrees C within the frequency
      range 3-11 MHz. Values of integrated backscatter coefficient significantly
      decreased between 80 and 130 days gestation (from -73.0 +/- 5.7 dB to -84.0 +/-
      0.9 dB between 3 to 7 MHz and from -70.0 +/- 0.8 dB to -81.3 +/- 0.5 dB between 5
      to 11 MHz). Values of the integrated spectral ratio indicate that the
      echogenicity of the lung is greater than that of the liver. These values also
      decreased between 80 and 130 days gestation (from 10.5 +/- 1.1 dB to 5.1 +/- 0.9
      dB between 3 to 7 MHz and from 10.0 +/- 0.8 dB to -6.4 +/- 0.6 dB between 5 to 11
      MHz). Texture analysis showed that the K distribution is a good model to describe
      the envelope of the backscattered signals from the lung and the values of the
      effective density of scatterers that decrease between 80 and 130 days. These
      trends seem to be linked to the maturation of the microstructure of the lung and,
      particularly, to the development of respiratory terminal structures.

PMID- 11316525
TI  - Assessment of the myocardial changes in heart transplant recipients without
      evident acute myocardial rejection by integrated backscatter: comparison with
      simultaneous dobutamine stress echocardiography and (201)thallium spect.
AB  - Cardiomyocyte hypertrophy and interstitial fibrin deposition develop in cardiac
      allografts and contribute to the functional changes of transplanted hearts. We
      hypothesized that integrated backscatter (IBS) can detect these myocardial
      changes. A total of 32 heart transplant recipients with either no or mild acute
      rejection (International Society of Heart and Lung Transplantation grade IA) were
      enrolled in this study. IBS data of myocardium were collected immediately before
      simultaneous dobutamine stress echocardiography (DSE) and (201)thallium imaging.
      Coronary angiography and endomyocardial biopsy were also performed. Coronary
      angiography showed diffuse narrowing in 1 patient who also had abnormal results
      of IBS, DSE, and thallium results. In the other 31 patients with patent coronary
      arteries, there were 3 patients (10%) with abnormal DSE results, 19 patients
      (61%) with abnormal IBS patterns, and 16 patients (52%) with reversible thallium
      perfusion defects. Of the patients, 44% had cardiomyocyte hypertrophy and 56%
      interstitial fibrin deposition. There were significant differences in the
      prevalence of (201)thallium perfusion defects and serum cyclosporine levels
      between patients with and without abnormal IBS patterns. Pathologic changes were
      also associated with abnormal IBS patterns (p = 0.01). However, there was no
      association between abnormal IBS and DSE results. By multiple logistic regression
      analysis, the abnormal IBS patterns were associated inversely with serum
      cyclosporine level (p = 0.028). In conclusion, abnormal IBS patterns are
      associated significantly with perfusion heterogeneity and pathologic changes in
      heart transplant recipients without evident acute myocardial rejection. There is
      no association between abnormal IBS patterns and dobutamine-induced dyssynergy in
      these patients. IBS provides a noninvasive approach for detection of myocardial
      changes in transplanted hearts without evident acute rejection.

PMID- 11316527
TI  - Neurovascular coupling and cerebral autoregulation can be described in terms of a
      control system.
AB  - Neurovascular coupling and cerebral autoregulation are important and fast
      mechanisms for maintaining an adequate blood supply to the brain. It was
      suggested that both mechanisms follow a common control system. The aim of our
      study was to describe neurovascular coupling and cerebral autoregulation in
      mathematical terms of a control system and to test the aforementioned hypothesis.
      We analyzed the input-output dynamics of neurovascular coupling (flicker light
      test) and cerebral autoregulation (leg cuff test) in terms of a control system,
      and compared both systems. A transcranial Doppler device was used to measure
      continuously the blood flow velocity changes in young healthy volunteers who
      lacked vascular risk factors. For both tests, a control system model with only
      four parameters was sufficient to allow the vascular reaction to be described in
      all (rate time, undamped natural angular frequency, attenuation, gain). All
      parameters were identical for both control systems, except for gain, which is not
      directly comparable because, in the flicker light test, input function was not
      measured but assumed as a unit step function in each volunteer. This new method
      permits description of the regulation of cerebral blood flow using a control loop
      with four parameters. For the first time, these parameters allowed a
      demonstration that cerebral autoregulation and neurovascular coupling could be
      governed by the same control system.

PMID- 11316526
TI  - Dynamic behaviour of the common femoral artery: age and gender of minor
      importance.
AB  - The distensibility of elastic arteries has been extensively studied, while
      studies of muscular arteries are sparse. The influences of age and gender on the
      mechanical properties of the common femoral artery (CFA) were studied. The
      pulsatile diameter changes of the CFA were noninvasively measured using echo
      tracking sonography in 173 healthy volunteers (95 females, 78 males, range 7-81
      years). In combination with blood pressure measurements, stiffness (beta) and
      pressure strain elastic modulus (Ep) were calculated. Neither beta nor Ep was
      related to age or gender and a considerable interindividual variation was
      present. The CFA diameter increased with age. In conclusion, the distensibility
      of this muscular artery is not clearly affected by age or gender, although the
      diameter increases with age. This indicates remodelling of the arterial wall and
      an impact of vascular smooth muscles on long-term wall mechanics. Thus, there
      appear to be fundamental differences in the dynamic behaviour of the common
      femoral artery when compared to elastic arteries, such as the aorta and the
      common carotid artery.

PMID- 11316528
TI  - Measurement of cardiac function in conscious rats.
AB  - The goal of this study was to establish that 1. blood velocity profile in the rat
      aorta is parabolic, and 2. measure of left ventricular thickening fraction can be
      used in rats. Spontaneously hypertensive and normotensive Wistar Kyoto rats were
      instrumented with a 20-MHz pulsed Doppler flow probe around the thoracic aorta
      and a 20-MHz pulsed Doppler thickening probe on the left ventricle. Doppler
      frequency shifts were measured throughout the entire aorta diameter, and
      individual blood velocity profiles were constructed. It was demonstrated that
      blood velocity in the ascending aorta of rats is laminar; therefore, cardiac
      output can be measured using the pulsed Doppler method. In Wistar Kyoto rats,
      left ventricular thickening fraction was 24 +/- 1% and 25 +/- 1%, 2 and 3 weeks
      following surgery. In spontaneously hypertensive rats, left ventricular
      thickening fraction was 22 +/- 2%. Halothane depressed left ventricular
      thickening fraction, whereas isoproterenol increased left ventricular thickening
      fraction in conscious rats. Thus, pulsed Doppler technique is a valuable tool for
      evaluating cardiovascular function in conscious rats.

PMID- 11316529
TI  - Patient motion compensation during transthoracic 3-D echocardiography.
AB  - Bulk patient motion during transthoracic 3-D echocardiography (3DE) produces
      image plane misregistration and errors in left ventricular (LV) volume and
      ejection fraction (EF). To correct for patient motion, we used a magnetic
      locating system to track both the ultrasound transducer and the chest wall of the
      patient, so images could be registered in a patient-centered coordinate system
      ("correction"). Fourteen subjects each underwent 3DE, with deliberate patient
      motion, to measure LV volume and EF. Results were compared to magnetic resonance
      imaging (MRI). Without correction, 3DE differed significantly from MRI (EF: r =
      0.78, SEE = 5.8%). Application of correction increased 3DE accuracy, despite
      patient motion (EF: r = 0.91, SEE = 3.7%), to a level comparable to that of 3DE
      in the absence of motion (EF: r = 0.93, SEE = 3.5%). Patient motion during 3DE
      examination can be corrected using a magnetic spatial location system.

PMID- 11316530
TI  - In vitro simulation and quantification of temporal jitter artifacts in ECG-gated
      dynamic three-dimensional echocardiography.
AB  - The image quality of dynamic 3-D echocardiography is limited by temporal jitter
      artifacts that result from the asynchronous acquisition of video frames with the
      cardiac cycle. This paper analyzes the source and extent of these artifacts using
      in vitro studies. Dynamic 3-D images of a myocardial motion phantom were
      reconstructed and analyzed for eight cardiac motion patterns. The extent of
      temporal jitter artifacts was quantified, first, from the images by computing
      temporal jitter maps and, second, predicted from the motion waveforms. Temporal
      jitter appeared as a pattern of streak artifacts converging at the axis of
      rotation of the imaging plane, for the rotational scanning approach used in our
      study. The results of the experimental analysis techniques were compared with the
      waveform analysis using linear regression analysis. The least squares line showed
      good correlation between the data (r > 0.9) and its deviation from the line of
      identity was calculated to be <9%.

PMID- 11316531
TI  - High-resolution functional imaging with ultrasound contrast agents based on RF
      processing in an in vivo kidney experiment.
AB  - Knowledge of the relative tissue perfusion distribution is valuable in the
      diagnosis of numerous diseases. Techniques for the assessment of the relative
      perfusion distribution, based on ultrasound (US) contrast agents, have several
      advantages compared to established nuclear techniques. These are, among others, a
      better spatial and temporal resolution, the lack of exposure of the patient to
      ionizing radiation and the relatively low cost. In the present study, US
      radiofrequency (RF) image sequences are acquired, containing the signal intensity
      changes associated with the transit of a bolus contrast agent through the
      microvasculature of a dog kidney. The primary objective is to explore the
      feasibility of calculating functional images with high spatial resolution. The
      functional images characterize the transit of the contrast agent bolus and
      represent distributions of peak time, peak value, transit time, peak area, wash
      in rate and wash-out decay constant. For the evaluation of the method, dog
      experiments were performed under optimized conditions where motion artefacts were
      minimized and an IA injection of the contrast agent Levovist was employed. It was
      demonstrated that processing of RF signals obtained with a 3.5-MHz echo system
      can provide functional images with a high spatial resolution of 2 mm in axial
      resolution, 2 to 5 mm in lateral resolution and a slice thickness of 2 mm. The
      functional images expose several known aspects of kidney perfusion, like
      perfusion heterogeneity of the kidney cortex and a different peripheral cortical
      perfusion compared to the inner cortex. Based on the findings of the present
      study, and given the results of complimentary studies, it is likely that the
      functional images reflect the relative perfusion distribution of the kidney.

PMID- 11316532
TI  - Quantitative assessment of in vitro jets based on three-dimensional color Doppler
      reconstruction.
AB  - Three-dimensional (3-D) color Doppler imaging of flow jets was performed to
      investigate the effects of flow rate and orifice size on jet volumes. Flow jets
      were generated using a flow model to simulate mitral regurgitation. This flow
      model consisted of a ventricular chamber, a valvular plate and an atrial chamber.
      Steady flow was driven through circular orifices having diameters of 2.5, 3.5,
      4.5, and 6 mm, respectively, with flow rates of 5, 10, 15, 20, and 25 mL/s to
      form free jets in the atrial chamber. An ATL Ultramark 9 HDI system was used to
      perform 3-D color Doppler imaging of the flow jets. A transesophageal probe was
      rotated by a stepper motor to create 3-D color Doppler images of the jets. The
      color jet volumes for different hemodynamic conditions were measured and then
      compared with the theoretical predictions. Results showed that the jet volume
      estimated from the 3-D color Doppler was directly proportional to the flow rate
      and inversely proportional to the orifice size. The estimated jet volumes
      correlated well (r > 0.95) with theoretical predictions. This study supports the
      use of color jet volume as a parameter to quantify mitral regurgitation.

PMID- 11316533
TI  - Construction and geometric stability of physiological flow rate wall-less
      stenosis phantoms.
AB  - Wall-less flow phantoms are preferred for ultrasound (US) because tissue
      mimicking material (TMM) with good acoustical properties can be made and cast to
      form anatomical models. The construction and geometrical stability of wall-less
      TMM flow phantoms is described using a novel method of sealing to prevent leakage
      of the blood-mimicking fluid (BMF). Wall-less stenosis flow models were
      constructed using a robust agar-based TMM and sealed using reticulated foam at
      the inlet and outlet tubes. There was no BMF leakage at the highest flow rate of
      2.8 L/min in 0%, 35% and 57% diameter reduction stenoses models. Failure of the
      75% stenosis model, due to TMM fracture, occurred at maximum flow rate of 2 L/min
      (mean velocity 10 m/s within the stenosis). No change of stenosis geometry was
      measured over 4 days. The construction is simple and effective and extends the
      possibility for high flow rate studies using robust TMM wall-less phantoms.

PMID- 11316534
TI  - Nonlinear native propagation effects of diagnostic ultrasound computed and
      measured in blood.
AB  - Nonlinear propagation effects produced by focused pulses in blood were measured
      over a 20-cm range, being inspired by diagnostic applications in cardiology. The
      initial and maximum pressures applied during measurements in blood were equal to
      0.40 MPa(pp) and 0.76 MPa(pp), while the pressure estimated at the patient body
      surface equalled 0.70 MPa(pp). Measurements of the frequency characteristic and
      the linearity of the ultrasonic probe used in experiments were performed in
      water. A numerical procedure developed previously was applied in blood to
      calculate the pressure distribution of its first and second harmonics along the
      beam axis. The comparison of numerical and measured distributions in blood at a
      temperature of 37 degrees C showed rather good agreement. Using numerical
      methods, a proportional growth of the second harmonic with the increased applied
      initial pressure was first observed, and finally the maximum limiting effect was
      found. In this way, much higher level of harmonics could be obtained. However,
      there arise the questions of the transmitting system construction and of the
      nonuniform resolution in the case of harmonic imaging when increasing the applied
      initial pressure.

PMID- 11316535
TI  - Inhibition of carotid artery neointimal formation with intravenous microbubbles.
AB  - Because therapeutic gene products such as synthetic antisense
      oligodeoxynucleotides (ODN) bind to albumin-coated microbubbles, we sought to
      determine whether IV perfluorocarbon-exposed sonicated dextrose albumin (PESDA)
      microbubbles could target their delivery to the carotid artery following balloon
      injury. In 5 pigs, the concentration of ODN taken up within the carotid vascular
      wall was found to be significantly increased when the IV antisense (ODN) was
      administered bound to PESDA (ODN-PESDA), and while transcutaneous low-frequency
      (20 kHz) ultrasound was applied over the carotid artery. Based on these results,
      a chronic model was then developed, in which 21 pigs received either IV ODN
      PESDA, ODN alone, or control, following carotid balloon injury. At 30 days
      following balloon injury, percent area stenosis was only 8 +/- 2% in the ODN
      PESDA groups compared to 19 +/- 8% and 28 +/- 3% in the other groups (p < 0.01).
      IV PESDA may be a method of noninvasively targeting the delivery of therapeutic
      genes.

PMID- 11316536
TI  - Superthreshold behavior of ultrasound-induced lung hemorrhage in adult mice and
      rats: role of pulse repetition frequency and exposure duration.
AB  - Superthreshold behavior for ultrasound-induced lung hemorrhage was investigated
      in adult mice and rats at an ultrasound center frequency of 2.8 MHz to assess the
      role of pulse repetition frequency and exposure duration. One hundred fifty, 6-7
      week-old female ICR mice and 150 10-11-week-old female Sprague-Dawley rats were
      each divided into 15 exposure groups (10 animals per group) for a 3 x 5 factorial
      design (3 exposure durations of 5, 10, and 20 s and 5 pulse repetition
      frequencies of 25, 50, 100, 250, and 500 Hz). The in situ (at the pleural
      surface) peak rarefactional pressure of 12.3 MPa and the pulse duration of 1.42
      micros were the same for all ultrasonically-exposed animals. In addition, 15 sham
      exposed mice and 15 sham exposed rats were included into both studies. In each
      study of 165 animals, the exposure conditions were randomized. The lesion depth
      and surface area were measured for each animal, as well as the percentage of
      animals with lesions per group. The characteristics of the lesions produced in
      mice and rats were similar to those described in studies by our research group
      and others, suggesting a common pathogenesis for the initiation and propagation
      of the lesions at the gross and microscopic levels. The proportion of lesions in
      both species was related statistically to pulse repetition frequency (PRF) and
      exposure duration (ED), with the exception that PRF in rats was not quite
      significant; the PRF x ED interaction (number of pulses) for lesion production
      was not significant for either species. The PRF, but not ED, significantly
      affected lesion depth in both species; the PRF x ED interaction for depth was not
      significant for either species. Both PRF and ED significantly affected lesion
      surface area in mice, while neither affected area in rats; the PRF x ED
      interaction for surface area was not significant for either species.

PMID- 11316537
TI  - Absence of spinal response to extracorporeal shock waves on the endogenous opioid
      systems in the rat.
AB  - Extracorporeal shock wave therapy (ESWT) seems to be a new therapeutic strategy
      for chronic pain due to tendopathies. Neurophysiological mechanisms of action for
      pain relief following ESWT are still unknown. The aim of this study was to
      investigate if the analgesic effect of ESWT is caused by modulation of the
      endogenous spinal opioid system. Rats were treated with two different energy flux
      densities (0.04 and 0.11mJ/mm(2)) and immunohistochemical analysis of met
      enkephalin (MRGL) and dynorphin (Dyn) was performed at 4 or 72 h after ESWT. ESWT
      had no modulatory influence on the expression of the spinal opioid systems.
      Different energy doses or repetitive treatment did not alter MRGL or Dyn
      immunoreactivity in the spinal cord. Furthermore, a delayed effect of ESWT at 72
      h after treatment was not detectable. We conclude from these findings that the
      analgesic effects of ESWT treatment are not supported by endogenous opioids.

PMID- 11316538
TI  - Distribution of artificially-produced microembolic signals into the cerebral
      circulation.
AB  - According to clinical observations, cardiogenic embolism occurs more often in the
      anterior than in the posterior cerebral circulation. An ultrasound (US) contrast
      agent was used to artificially produce microembolic signals (MES) to imitate the
      intracranial distribution of systemic emboli. Systemic microemboli were simulated
      by IV administered US agent (Levovist(R) 300 mg/mL as bolus). A total of 20
      patients were monitored by means of transcranial Doppler sonography (TCD), 3 min
      after the injection, with a 2-MHz transducer simultaneously at 50 mm (middle
      cerebral artery, MCA, on one side) and 90 mm (basilar artery, BA). Four 3-min
      recordings were done (two of the right MCA, two of the left MCA, with the BA,
      respectively). Three observers and an automatic detection system independently
      performed an off-line analysis. A total of 160 recordings were analyzed. The mean
      numbers of detected high-intensity transient signals (HITS) were 34.5 +/- 28.2 in
      the right MCA (simultaneously registered HITS in the BA: 9.4 +/- 16.8) and 39.1
      +/- 34.2 in the left MCA (simultaneously registered HITS in the BA: 12.2 +/-
      14.5). Only 21.4 to 23.7% of all HITS were recorded in the BA. Microembolic
      signals artificially produced by means of US contrast agent made it possible to
      mimic the physiologic distribution of small embolic particles. In future, these
      might help to investigate the distribution of systemic emboli in different
      vascular territories in various pathologic conditions of the cerebral blood flow.

PMID- 11316539
TI  - Measurement of the speed of sound in ethanol/water mixtures.
AB  - Ethanol/water mixtures are used commonly as a propagation medium in test objects
      to calibrate the measurement facilities of ultrasound (US) imaging systems. The
      speed of sound c in the mixture should be known, preferably with an accuracy of
      +/-0.1% where clinical measurements to +/-1% are required. This article describes
      measurements of c in several ethanol/water mixtures over a range of temperatures
      using a simple pulse superposition technique, which gives an estimated
      measurement uncertainty of 0.1%. The measurements show that, at 20 degrees C, a
      mixture of 9.5 +/- 0.25% ethanol by volume in distilled water is required to give
      a speed of 1540 +/- 1.5 m s(-1). However, to achieve this accuracy, the
      temperature of the mixture must be maintained in the range 20 degrees +/- 0.75
      degrees C.

PMID- 11316540
TI  - Preoperative hyperfractionated radiotherapy with concurrent chemotherapy in
      resectable esophageal cancer.
AB  - PURPOSE: To evaluate the local control rates, survival rates, and patterns of
      failure for esophageal cancer patients receiving preoperative concurrent
      chemotherapy and hyperfractionated radiotherapy followed by esophagectomy.
      METHODS AND MATERIALS: From May 1993 through January 1997, 94 patients with
      resectable esophageal cancers received continuous hyperfractionated radiation
      (4,800 cGy/40 fx/4 weeks), with concurrent FP chemotherapy (5-FU 1 g/m(2)/day,
      days 2-6, 30-34, CDDP 60 mg/m(2)/day, days 1, 29) followed by esophagectomy 3-4
      weeks later. If there was evidence of disease progression on preoperative re
      evaluation work-up, or if the patient refused surgery, definitive
      chemoradiotherapy was delivered. Minimum follow-up time was 2 years. RESULTS; All
      patients successfully completed preoperative treatment and were then followed
      until death. Fifty-three patients received surgical resection, and another 30
      were treated with definitive chemoradiotherapy. Eleven patients did not receive
      further treatment. Among 91 patients who received clinical reevaluation, we
      observed 35 having clinical complete response (CR) (38.5%). Pathologic CR rate
      was 49% (26 patients). Overall survival rate was 59.8% at 2 years and 40.3% at 5
      years. Median survival time was 32 months. In 83 patients who were treated with
      surgery or definitive chemoradiotherapy, the esophagectomy group showed
      significantly higher survival, disease-free survival, and local disease-free
      survival rates than those in the definitive chemoradiation group. CONCLUSION:
      Preoperative chemoradiotherapy in this trial showed improved clinical and
      pathologic tumor response and survival when compared to historical results.
      Patients who underwent esophagectomy following chemoradiation showed decreased
      local recurrence and improved survival and disease-free survival rates compared
      to the definitive chemoradiation group.

PMID- 11316541
TI  - Apoptosis and bcl-2 expression as predictors of survival in radiation-treated non
      small-cell lung cancer.
AB  - OBJECTIVES: We assessed the role of apoptosis and the expression of bcl-2, p53,
      and c-myc oncoproteins in pretreatment histologic specimens as a predictor of
      response to radiation therapy and survival in non-small-cell lung cancer (NSCLC)
      patients. METHODS: Pretreatment biopsy specimens of 68 patients with NSCLC (62
      squamous cell carcinoma, 6 adenocarcinoma) were stained with hematoxylin and
      eosin. From 5 high-powered fields, the apoptotic index (AI) was calculated as the
      ratio of apoptotic tumor cells to the total number of tumor cells. Bcl-2, p53,
      and c-myc oncoprotein expression was detected by immunohistochemical staining.
      RESULTS: Twenty-nine cases showed partial or complete remission, whereas 39
      showed no response. AI ranged from 0.2 to 12.0% (mean +/- SD; 4.3 +/- 2.6%,
      median 4.0%). There was no difference in AI between responders (4.0 +/- 2.3) and
      nonresponders (4.5 +/- 2.8, p > 0.05). However, in the responders, AI was
      correlated with the degree of change in tumor volume (r = 0.41, p < 0.05). In an
      analysis of 53 subjects who survived more than 1 month after the completion of
      radiation therapy, the patients with a higher AI (n = 27, MST = 22.8 m) survived
      longer than those with a lower AI (n = 26, MST = 9.2, log-rank, p = 0.03).
      Patients expressing bcl-2 had poorer survival (n = 22, MST = 6.0 m) than patients
      without bcl-2 (n = 31, 22.8 m, p < 0.003). According to multivariate analysis,
      three variables, bcl-2 expression, AI, and response to radiation, were
      independent prognostic factors for survival. CONCLUSION: A low level of
      spontaneous apoptosis and expression of apoptosis blocking bcl-2 protein in
      pretreatment histology predict a poor prognosis for radiation-treated NSCLC
      patients.

PMID- 11316542
TI  - Hyperfractionated radiation therapy and concurrent low-dose, daily
      carboplatin/etoposide with or without weekend carboplatin/etoposide chemotherapy
      in stage III non-small-cell lung cancer: a randomized trial.
AB  - PURPOSE: To investigate whether the addition of weekend chemotherapy consisting
      of carboplatin/etoposide to hyperfractionated radiation therapy (Hfx RT) and
      concurrent daily carboplatin/etoposide offers an advantage over the same Hfx
      RT/daily carboplatin/etoposide. METHODS AND MATERIALS: A total of 195 patients
      (Group I, 98; Group II, 97) were treated with either Hfx RT to a total tumor dose
      of 69.6 Gy via 1.2 Gy b.i.d. fractionation and daily 50 mg each of carboplatin
      and etoposide during the RT course (Group I) or the same Hfx RT with daily
      carboplatin/etoposide consisting of 30 mg each of carboplatin and etoposide and
      with weekend (Saturdays and Sundays) 100 mg each of carboplatin and etoposide
      during the RT course (Group II). RESULTS: No difference was found regarding
      median survival time and 5-year survival rates (20 vs. 22 months and 20% vs. 23%;
      p = 0.57). Median time to local progression was 20 and 19 months, respectively,
      while 5-year local progression-free survival rates were 28% and 27%, respectively
      (p = 0.66). Also, there was no difference regarding either median time to distant
      metastasis and 5-year distant metastasis-free survival (21 vs. 25 months and 29%
      vs. 34%, p = 0.29). There was no difference in the incidence of various
      nonhematologic toxicities between the two treatment groups, but patients treated
      with the weekend CHT had significantly more high-grade (> or = 3) hematologic
      toxicity (p = 0.0046). Late high-grade toxicity was not different between the two
      treatment groups. CONCLUSION: The addition of weekend carboplatin/etoposide did
      not improve results over those obtained with Hfx RT and concurrent low-dose,
      daily carboplatin/etoposide, but it led to a higher incidence of acute high-grade
      hematologic toxicity.

PMID- 11316543
TI  - Nuclear expression of human apurinic/apyrimidinic endonuclease (HAP1/Ref-1) in
      head-and-neck cancer is associated with resistance to chemoradiotherapy and poor
      outcome.
AB  - PURPOSE: HAP1/Ref-1 endonuclease is involved in the repair of DNA strand breaks
      and in the activation of DNA binding of several transcription factors. HAP1 is
      also a potent activator of wild type p53. It therefore has multiple possible
      roles in the response of human cancer to radiotherapy and chemotherapy. METHODS
      AND MATERIALS: The nuclear expression of HAP1 and p53 proteins was studied by
      immunohistochemistry in paraffin-embedded material from 95 patients with locally
      advanced squamous cell head-and-neck cancer (HNC) treated with radical
      radiotherapy (38 cases with induction platinum-based chemotherapy and 57 with
      concurrent platinum chemoradiotherapy). RESULTS: HAP1 was present in the nuclei
      of normal epithelium and stromal cells. Loss of HAP1 nuclear expression was
      frequently noted in cancer cells. Tumors with high HAP1 nuclear expression (% of
      positive cells > mean; mean = 11%) were of good differentiation (p = 0.06) and
      presented frequently with advanced nodal disease (p = 0.01). High nuclear HAP1
      expression was significantly associated with poor complete response rate (p =
      0.00001), shorter local relapse-free interval (p < 0.0001), and poorer survival
      (p < 0.0008). HAP1 nuclear reactivity was inversely associated with p53 nuclear
      accumulation (p = 0.003). The inverse correlation between HAP1 expression and
      prognosis was independent of p53 status. CONCLUSION: HAP1 nuclear expression in
      HNC is inversely associated with p53 nuclear accumulation and directly related to
      resistance to chemoradiotherapy and poor survival. Further clinical investigation
      is required to confirm these findings.

PMID- 11316544
TI  - The relation of CT-determined tumor parameters and local and regional outcome of
      tonsillar cancer after definitive radiation treatment.
AB  - PURPOSE: To investigate the value of CT-derived tumor parameters as predictor of
      local and regional outcome of tonsillar squamous cell carcinoma treated by
      definitive radiation therapy. METHODS AND MATERIALS: The pretreatment CT studies
      of 112 patients with tonsillar squamous cell carcinoma were reviewed. After
      redigitizing the films, primary and nodal tumor volume was calculated with the
      summation-of-areas technique. The nodal CT aspect was graded using a 3-point
      scale (homogenous, inhomogeneous, and necrotic). Mean follow-up time was 33
      months. Actuarial statistical analysis of local and regional outcome was done for
      each of the covariates; multivariate analysis was performed using Cox's
      proportional hazards model. RESULTS: In the actuarial analysis, CT-determined
      primary tumor volume was significantly correlated with local recurrence rate (p <
      0.05) when all patients were considered, but primary tumor volume did not predict
      local control within the T2, T3, and T4 category. CT-determined nodal volume was
      significantly related to regional outcome (p < 0.01), but nodal density was not.
      Total tumor volume was not significantly related to locoregional outcome (p =
      0.1). In the multivariate analysis, the T and N categories were the independent
      predictors of local and regional outcomes, respectively. CONCLUSION: Compared to
      other head-and-neck sites, primary and nodal tumor volume have only marginal
      predictive value regarding local and regional outcome after radiation therapy in
      tonsillar cancer.

PMID- 11316545
TI  - Hyperfractionated chemoradiation with carbogen breathing, with or without
      erythropoietin: a stepwise developed treatment schedule for advanced head-and
      neck cancer.
AB  - PURPOSE: To investigate the influence of carbogen breathing on chemoradiation and
      the effects of erythropoietin on transfusions. METHODS AND MATERIALS: From March
      1996 to April 2000, 42 (4 Stage III and 38 Stage IV) patients with head and neck
      cancer were treated with a twice-a-day hyperfractionated schedule. Each fraction
      consisted of 5 mg/m(2) of carboplatin plus 115 cGy with carbogen breathing.
      Treatment was given 5 days per week up to total doses of 350 mg/m(2) of
      carboplatin plus 8050 cGy in 7 weeks. Anemia was treated either by transfusion or
      by erythropoietin. RESULTS: Forty-one patients tolerated the treatment as
      scheduled. All patients tolerated the planned radiation dose. Five transfusions
      were given in the first group, but no transfusion was needed in the
      erythropoietin group. Local toxicities remained at the level expected with
      irradiation alone. Chemotherapy toxicity was moderate. Forty-two complete
      responses were achieved. At two years actuarial local control, cause-specific
      survival and overall survival are respectively 85%, 69%, and 68%. At four years
      estimated probabilities of local control, cause-specific survival and overall
      survival are also 85%, 69%, and 68%. CONCLUSIONS: These results compare favorably
      with those of most reported studies. The addition of carbogen breathing appears
      to improve the results of chemoradiation alone. Erythropoietin therapy avoided
      transfusions.

PMID- 11316546
TI  - Squamous cell carcinomas metastatic to cervical lymph nodes from an unknown head
      and-neck mucosal site treated with radiation therapy alone or in combination with
      neck dissection.
AB  - PURPOSE: The present study presents the experience at the University of Florida
      with treatment of patients with squamous cell carcinomas (SCC) metastatic to
      cervical lymph nodes from an unknown head-and-neck mucosal (H&NM) site with
      radiotherapy (RT) alone or in combination with neck dissection (ND). METHODS AND
      MATERIALS: The study included 126 patients treated with curative intent from 1964
      to 1997. All patients had follow-up for at least 2 years. No patients were lost
      to follow-up. RESULTS: Twelve patients (10%) developed SCC in H&NM sites at 0.5
      to 10.9 years (median, 1.8 years). The rate of developing carcinomas in H&NM
      sites at 5 years was 13%. Histologic differentiation significantly affected the
      rate of developing carcinomas in H&NM sites in multivariate analysis. Sixteen
      patients (13%) had persistent nodal disease and 12 patients (10%) developed
      recurrent nodal disease at 0.5 to 10.9 years (median, 1.1 years). The nodal
      control rate at 5 years was 78%. Nodal size, N stage, and planned ND
      significantly affected the rate of nodal control in multivariate analysis.
      Nineteen patients (15%) developed distant metastasis at 0.2-5.1 years (median,
      0.9 years). The distant metastases rate at 5 years was 14%. Extracapsular
      extension and RT dose significantly affected the risk of distant metastases in
      multivariate analysis. The overall absolute survival rate at 5 years was 47%.
      Extracapsular extension, N stage, RT dose for H&NM sites, and planned ND
      significantly affected absolute survival in multivariate analysis. The rate of
      cause-specific survival at 5 years was 67%. Extracapsular extension, nodal size,
      N stage, overall treatment time, and planned ND significantly affected cause
      specific survival in multivariate analysis. Eight patients (6%) had severe
      postoperative complications and 6 patients (5%) had severe late complications.
      CONCLUSION: The present study supports the effectiveness of RT in lowering the
      rate of developing carcinomas in the H&NM sites.

PMID- 11316547
TI  - Palliative radiotherapy in recurrent head-and-neck tumors by a percutaneous
      superfractionated treatment schedule.
AB  - PURPOSE: A frequent problem in treatment of patients with head-and-neck tumors is
      recurrence in pre-irradiated areas, thus limiting dose for another full-course
      radiotherapy. We present our experience with a percutaneous superfractionated
      short-term radiotherapy regimen that may be useful for palliative irradiation.
      METHODS AND MATERIALS: Twenty-three patients with head-and-neck tumor recurrence
      after radiotherapy or extensive tumor growth have been treated by a
      superfractionated regimen. At each of two subsequent days, eight fractions of 1
      Gy were applied with an interfraction interval of 1 h, resulting in a total dose
      of 16 Gy. Time between the last fraction of the first day and the first fraction
      of the second day was 17 h. RESULTS: In 16 of 23 patients (70%), our irradiation
      schedule could achieve a palliative effect such as tumor necrosis or reduction of
      swelling or pain. Seven patients showed erythema (WHO I) at the end of the second
      day. Neither mucositis nor late effects of treatment were observed. CONCLUSIONS:
      Our superfractionated schedule is feasible without severe acute side reactions
      and can achieve a palliative effect in advanced or recurrent head-and-neck
      cancer.

PMID- 11316548
TI  - Methods of bolusing the tracheostomy stoma.
AB  - PURPOSE: The tracheostomy stoma is a potential site of recurrence for patients
      who have subglottic cancer or subglottic spread of cancer. In these patients, it
      is important that the anterior supraclavicular field does not underdose the
      posterior wall of the tracheostomy stoma when using a 6-MV anterior photon field.
      Conventionally, this problem is surmounted with placement of a plastic
      tracheostomy tube, which is uncomfortable for the patient, potentially traumatic,
      and can interfere with vocalization via a tracheal esophageal puncture. Our study
      was designed to investigate the dosimetry of this region and see if alternate
      methods would be effective. METHODS AND MATERIALS: A phantom was constructed
      using a No. 6 tracheostomy tube as the model for the tracheostomy curvature and
      size. Using the water-equivalent phantom, film dosimetry, and films oriented
      parallel to the en face field, we investigated the dose at the depth of the
      surface of the posterior wall of the phantom's tracheostomy stoma. Dose was
      measured both in space and at the tissue interface by scanning points of interest
      both horizontally and vertically. We measured doses with a No. 6 and No. 8
      plastic tracheostomy tube, either 0.5 cm and 1.0 cm of bolus (1-cm airhole) with
      no tracheostomy tube, as well as 0.3 cm and 0.6 cm tissue-equivalent Aquaplast
      (Med-Tec Co., Orange City, Iowa) over the tracheostomy. Dosimetry at the
      posterior interface was confirmed using thermoluminescent dosimeters. RESULTS:
      Three mm and 6 mm of Aquaplast produced a posterior tracheal dose of 93% and
      100%. CONCLUSION: There is no need for these patients to wear a temporary plastic
      tracheostomy tube during their external radiation therapy. Aquaplast should allow
      better position reproducibility, reduce trauma, not interfere with patient
      respiratory efforts, and be compatible with vocalization via a tracheal
      esophageal puncture.

PMID- 11316549
TI  - The Patterns of Care Survey of radiation therapy in localized prostate cancer:
      similarities between the practice nationally and in minority-rich areas.
AB  - PURPOSE: Over the last two decades, the chance for the cure of localized prostate
      cancer by radiation has been improved by the widespread use of PSA for early
      detection and by a number of technical advances in treatment delivery. This study
      was designed to determine whether the stage of presentation and the quality of
      radiation treatment delivered are comparable between Caucasian and minority
      patients nationally and within minority-rich areas. METHODS AND MATERIALS: A
      random survey conducted for the Patterns of Care Study in Radiation Oncology of
      80 facilities treating patients with radiation in the USA. Of these, 67 comprise
      the "National Survey" and 13 a "Minority-Rich" survey (>40% of treated patients
      are minorities). Nine hundred twenty-six men with localized prostate cancer were
      treated in 1994. Five hundred ninety-five were in the national and 331 in the
      minority-rich survey. The main outcome measures were the clinical features of
      Caucasian and minority men at presentation and technical characteristics of the
      treatment delivered to them. RESULTS: African-American men presented with more
      advanced disease (higher-presenting PSA and T-stage) than Caucasians in both the
      national and the minority-rich surveys. Hispanics also presented with later
      disease and could be grouped with African-American men rather than Caucasians.
      Overall the stage and PSA at presentation was earlier than seen in the previous
      Patterns of Care Study survey of 1989. The quality of treatment delivered has
      improved since 1989, with no distinction seen between those facilities sampled
      nationally and those within minority-rich areas. CONCLUSION: African-American and
      Hispanic men with prostate cancer present for therapy at a later stage than
      Caucasian men, but when they do, the treatment received is of comparable quality.

PMID- 11316550
TI  - Adenocarcinoma of the endometrium treated with combined irradiation and surgery:
      study of 437 patients.
AB  - PURPOSE: To identify prognostic factors and treatment toxicity in a series of
      operable endometrial adenocarcinomas. METHODS AND MATERIALS: Between November
      1971 and October 1992, 437 patients (pts) with endometrial carcinoma, staged
      according to the 1988 FIGO staging system (225 Stage IB, 107 Stage IC, 4 Stage
      IIA, 35 Stage IIB, 30 Stage IIIA, 6 Stage IIIB, and 30 Stage IIIC), underwent
      total abdominal hysterectomy and bilateral salpingo-oophorectomy without (n =
      140) or with (n = 297) pelvic lymph node dissection. The chronology of adjuvant
      RT was not randomized and depended on the usual practices of the surgical teams.
      Seventy-nine pts (Group I) received preoperative low-dose-rate uterovaginal
      brachytherapy (mean dose [MD]: 57 Gy). Three hundred fifty-eight pts (Group II)
      received postoperative RT. One hundred ninety-six pts received low-dose-rate
      vaginal brachytherapy alone (MD: 50 Gy). One hundred fifty-eight pts had external
      beam pelvic RT (MD: 46 Gy) followed by low-dose-rate vaginal brachytherapy (MD:
      17 Gy). Four pts had external beam pelvic RT alone (MD: 47 Gy). The mean follow
      up from the beginning of treatment was 128 months. RESULTS: The 10-year disease
      free survival rate was 86%. From 57 recurrences, only 12 were isolated
      locoregional recurrences. The independent factors decreasing the probability of
      disease-free survival were as follows: histologic type (clear-cell carcinoma, p =
      0.038), largest histologic tumor diameter >3 cm (p = 0.015), histologic grade (p
      = 0.008), myometrial invasion > 1/2 (p = 0.005), and 1988 FIGO staging system (p
      = 9.10(-8)). In Group II, the addition of external beam pelvic RT did not seem to
      independently improve vaginal or pelvic control. The postoperative complication
      rate was 7%. The independent factors increasing the risk of postoperative
      complications were stage FIGO (p = 0.02) and pelvic lymph node dissection (p =
      0.011). The 10-year rate for Grade 3 and 4 late radiation complications according
      to the LENT-SOMA scoring system was 3.1%. External beam pelvic RT independently
      increased the rate for Grade 3 and 4 late complication (RR: 5.6, p = 0.0096).
      CONCLUSION: Postoperative external beam pelvic RT increases the risk of late
      radiation complications. After surgical and histopathologic staging with pelvic
      lymph node dissection, in subgroup of "intermediate-risk" patients (Stage IA
      Grade 3, IB-C and II), postoperative vaginal brachytherapy alone is probably
      sufficient to obtain a good therapeutic index. Results for patients with Stage
      III tumor are not satisfactory.

PMID- 11316551
TI  - The relationship between radiation fields and regional lymph nodes in carcinoma
      of the breast.
AB  - PURPOSE: To examine the relationships between tangential, anterior, and posterior
      radiation fields and regional lymph nodes, including Levels I-III axillary and
      supraclavicular lymph nodes. METHODS AND MATERIALS: Fifty-five patients underwent
      computed tomography (CT) scanning in the supine treatment position, and radiation
      fields were developed to treat appropriate breast and lymphatic regions. After
      conventional fields had been selected, Levels I-III axillary and supraclavicular
      lymph nodes were identified on multiple CT slices performed at 3-5-mm intervals
      and their depths to the anterior skin surface and the anterior-posterior
      separations at multiple levels were measured. RESULTS: The mean depths of the
      Levels I-III axillary nodes were 4.6, 5.1, and 3.6 cm, respectively. The mean
      depth of the supraclavicular nodes was 3.9 cm. The mean anterior-posterior
      separations at these levels were 15.4, 15.2, 15.2, and 14.6 cm. The mean depths
      of the nodes, therefore, were well anterior to the midline. In the two-field
      treatment group, Level I axillary nodes appeared in the tangential portals in 9/9
      patients, either alone or with other lymph node groups. In the three-field group,
      Level I axillary nodes were in 16/16 tangential fields either alone or with level
      II nodes (8 patients). In 8 patients, Level III and the supraclavicular nodes
      were included in the anterior field and in the other 8, Levels II, III, and the
      supraclavicular nodes were in the anterior field. There was considerable
      variation in the nodal groups present in the posterior axillary boost field. No
      nodal groups were observed in 6 patients. CONCLUSION: There is considerable
      variation both in the depth of supraclavicular and axillary lymph nodes and the
      fields in which these nodal groups appear. To be certain that nodal groups which
      one plans to treat are actually treated, as well as to minimize nodal treatment
      when such treatment is not planned, it is recommended that before the placement
      of radiation fields, the nodal groups be outlined on a CT scan much as one would
      outline a tumor volume in other disease sites.

PMID- 11316552
TI  - Clinically evident fat necrosis in women treated with high-dose-rate
      brachytherapy alone for early-stage breast cancer.
AB  - PURPOSE: To investigate the incidence of and variables associated with clinically
      evident fat necrosis in women treated on a protocol of high-dose-rate (HDR)
      brachytherapy alone without external-beam whole-breast irradiation for early
      stage breast carcinoma. METHODS AND MATERIALS: From 6/1997 until 8/1999, 30 women
      diagnosed with Stage I or II breast carcinoma underwent surgical excision and
      postoperative irradiation via HDR brachytherapy implant as part of a multi
      institutional clinical Phase I/II protocol. Patients eligible included those with
      T1, T2, N0, N1 (< or = 3 nodes positive), M0 tumors of nonlobular histology with
      negative surgical margins, no extracapsular lymph-node extension, and a negative
      postexcision mammogram. Brachytherapy catheters were placed at the initial
      excision, re-excision, or at the time of axillary sampling. Direct visualization,
      surgical clips, ultrasound, or CT scans assisted in delineating the target volume
      defined as the excision cavity plus 2-cm margin. High activity (192)Ir (3-10 Ci)
      was used to deliver 340 cGy per fraction, 2 fractions per day, for 5 consecutive
      days to a total dose of 34 Gy to the target volume. Source position and dwell
      times were calculated using standard volume optimization techniques. Dosimetric
      analyses were performed with three-dimensional postimplant dose and volume
      reconstructions. The median follow-up of all patients was 24 months (range, 12-36
      months). RESULTS: Eight patients (crude incidence of 27%) developed clinically
      evident fat necrosis postimplant in the treated breast. Fat necrosis was
      determined by clinical presentation including pain and swelling in the treated
      volume, computed tomography, and/or biopsy. All symptomatic patients (7 of 8
      cases) were successfully treated with 3 to 12 months of conservative management.
      Continuous variables that were found to be associated significantly with fat
      necrosis included the number of source dwell positions (p = 0.04), and the volume
      of tissue which received fractional doses of 340 cGy, 510 cGy, and 680 cGy (p =
      0.03, p = 0.01, and p = 0.01, respectively). Other continuous variables including
      patient age, total excised tissue volume, tumor size, number of catheters, number
      of days the catheters were in place, planar separation, dose homogeneity index
      (DHI), and uniformity index (UI) were not significant. Discrete variables
      including the presence/absence of DCIS, sentinel versus full axillary nodal
      assessment, receptor status, presence/absence of diabetes, and the use of
      chemotherapy or hormone therapy were not found to have a significant association
      with the risk of fat necrosis. CONCLUSIONS: In this study of HDR brachytherapy of
      the breast tumor excision cavity plus margin, treatment was planned and delivered
      in accordance with the dosimetric parameters of the protocol resulting in a high
      degree of target volume dose homogeneity. Nonetheless, at a median follow-up of
      24 months, a high rate of clinically definable fat necrosis occurred. The overall
      implant volume as reflected in the number of source dwell positions and the
      volume of breast tissue receiving fractional doses of 340, 510, and 680 cGy were
      significantly associated with fat necrosis. Future dosimetric optimization
      algorithms for HDR breast brachytherapy will need to include these factors to
      minimize the risk of fat necrosis.

PMID- 11316553
TI  - Solitary plasmacytoma treated with radiotherapy: impact of tumor size on outcome.
AB  - PURPOSE: Solitary plasmacytoma (SP) is a rare presentation of plasma cell
      neoplasms. In contrast to multiple myeloma, long-term disease-free survival and
      cure is possible following local radiotherapy (RT), particularly for soft tissue
      presentations. In this study, we attempt to identify factors that predict for
      local failure, progression to multiple myeloma, and disease-free survival (DFS)
      in patients mainly managed with local RT. METHODS AND MATERIALS: We identified 46
      patients referred to the Princess Margaret Hospital between 1982 and 1993. The
      median age was 63 years (range 35-95), with a male:female ratio of 1.9:1. All
      patients had biopsy-proven SP (osseous: 32, soft tissue: 14). M-protein was
      abnormal in 19 patients (41%). All patients were treated with local RT (median
      dose 35 Gy), with 5 patients (11%) also receiving chemotherapy. Maximum tumor
      size pre-RT ranged from 0 to 18 cm (median 2.5). RESULTS: The 8-year overall
      survival, DFS, and myeloma-free rates were 65%, 44%, and 50%, respectively. The
      local control rate was 83%. Factors predictive of progression to myeloma (and
      poorer DFS) included bone presentation and older age. However, these two factors
      did not influence local control, which was affected by tumor size. All tumors < 5
      cm in bulk (34 patients) were controlled by RT. Anatomic location did not predict
      outcome; however, 3 of the 5 tumors arising in paranasal sinuses did not achieve
      local control. Lower RT dose (< or =35 Gy) was not associated with a higher risk
      of local failure. CONCLUSION: Solitary plasmacytomas are effectively treated with
      moderate-dose RT, although osseous tumors have a high rate of recurrence as
      systemic myeloma. Large tumor bulk locally (> or =5 cm) predicts for local
      failure. Combined chemotherapy and RT should be investigated in these high-risk
      patients to increase the local control rate and the cure rate.

PMID- 11316554
TI  - The efficacy of radiotherapy as postoperative treatment for desmoid tumors.
AB  - PURPOSE: The purpose of this study was to determine if radiotherapy is a
      beneficial adjuvant treatment after desmoid tumor resection. METHODS AND
      MATERIALS: A retrospective analysis was performed on 54 patients who underwent
      surgery without prior radiation at our institution between 1982 and 1998 to
      remove a desmoid tumor. Thirty-five patients had adjuvant radiation therapy after
      surgery, and 19 patients had surgery alone without immediate postoperative
      radiation. Sixteen of the 35 patients who underwent immediate postoperative
      radiation treatment had at least one prior resection before reoperation at our
      institution. Recurrence was defined as radiographic increase in tumor size after
      treatment. Follow-up interval (mean 39 months) and duration of local control were
      measured from the date of surgery at our institution. Potential prognostic
      factors for time to tumor progression were analyzed. RESULTS: Adjuvant treatment
      with radiation was the only significant prognostic factor for local control. The
      five-year actuarial local control rate was 81% for the 35 patients who underwent
      radiation in addition to surgery, compared to 53% for the 19 patients who
      underwent surgery alone (p = 0.018). For the patients who did not receive
      adjuvant radiation, only younger age at the time of surgery was associated with
      increased risk of failure (p = 0.035). Gross or microscopic margin status and
      number of prior operations were not detected as prognostic for local failure. For
      patients who did receive postoperative radiation, only abdominal location was
      associated with increased risk of failure (p = 0.0097). CONCLUSION: Radiation
      treatment as an adjuvant to surgery improved local control over surgery alone.
      Multiple operations before adjuvant radiation did not decrease the probability of
      subsequent tumor control. Radiation should be considered as adjuvant therapy to
      surgery if repeated surgery for a recurrent tumor would be complicated by a
      significant risk of morbidity.

PMID- 11316555
TI  - Long-term results of intraoperative electron beam radiotherapy for primary and
      recurrent retroperitoneal soft tissue sarcoma.
AB  - PURPOSE: This study assesses the long-term outcome of patients with
      retroperitoneal sarcoma treated by preoperative external beam radiotherapy,
      resection, and intraoperative electron beam radiation (IOERT). METHODS AND
      MATERIALS: From 1980 to 1996, 37 patients were treated with curative intent for
      primary or recurrent retroperitoneal soft tissue sarcoma. All patients underwent
      external beam radiotherapy with a median dose of 45 Gy. This was followed by
      laparotomy, resection, and IOERT, if feasible. Twenty patients received 10-20 Gy
      of IOERT with 9-15 MeV electrons. These patients were compared to a group of 17
      patients receiving preoperative irradiation without IOERT. RESULTS: The 5-yr
      actuarial overall survival (OS), disease-free survival, local control (LC), and
      freedom from distant disease of all 37 patients was 50%, 38%, 59%, and 54%,
      respectively. After preoperative irradiation, 29 patients (78%) underwent gross
      total resection. For 16 patients undergoing gross total resection and IOERT, OS
      and LC were 74% and 83%, respectively. In contrast, these results were less
      satisfactory for 13 patients undergoing gross total resection without IOERT. For
      these patients, OS and LC were 30% and 61%, respectively. Four patients
      experienced treatment-related morbidity. CONCLUSIONS: In selected patients, IOERT
      results in excellent local control and disease-free survival with acceptable
      morbidity.

PMID- 11316556
TI  - Stereotactic radiosurgery in the management of angiographically occult vascular
      malformations.
AB  - PURPOSE: To evaluate the role of stereotactic radiosurgery in the treatment of
      angiographically occult vascular malformations (AOVMs). METHODS AND MATERIALS:
      From 1987 to 1996, 21 patients, 10 males and 11 females, median age of 41 years
      (range: 7-75 years), with an intracerebral AOVM underwent stereotactic
      radiosurgery at our institution. All were considered at high risk for surgical
      intervention. The vascular lesions were located in the brainstem (17 patients),
      basal ganglia (2), occipital lobe (1), and cerebellum (1). Diagnosis was based on
      high-resolution magnetic resonance imaging (MRI). Clinical presentation at onset
      included previous intracerebral hemorrhage (20 patients) and epilepsy (1). All
      patients were treated with a linac-based radiosurgical technique. The median dose
      delivered was 25 Gy (range 13-50 Gy), typically prescribed to the 80-90% isodose
      surface (range 50-90%), which corresponded to the periphery of the vascular
      malformation. Patients were followed by clinical neurologic assessment and by MRI
      on a regular interval basis. RESULTS: Follow-up was obtained in 20 patients;
      clinical or MRI information was not available for 1 patient, and this patient was
      excluded from our analysis. At a median follow-up of 77 months (range: 4-141
      months), follow-up MRIs postradiosurgery do not demonstrate any changes in the
      appearance of the AOVM. Four patients developed an intracranial bleed at 4, 8,
      35, and 57 months postradiosurgery. Annual hemorrhage rates were considerably
      higher in the observation period preradiosurgery than postradiosurgery (30% vs.
      3.2%, p < 0.001). Complications postradiosurgery were observed in 4 patients.
      Three patients developed mild to moderate edema surrounding the radiosurgical
      target, expressed at 5, 8, and 24 months, respectively. In all cases, the edema
      was transient and resolved completely on subsequent MRIs. One of the 4 patients
      developed radiation necrosis 8 months after radiosurgery. CONCLUSION: The use of
      stereotactic radiosurgery in the treatment of AOVM continues to be controversial.
      Our results appear to show a reduction in the risk of symptomatic hemorrhage post
      treatment. Patients with previous history of hemorrhage or progressive neurologic
      deficit and small, well circumscribed lesions may benefit from a trial of
      stereotactic radiosurgery.

PMID- 11316557
TI  - Relationship between pattern of enhancement and local control of brain metastases
      after radiosurgery.
AB  - PURPOSE: A desired goal in the radiosurgery (RS) of brain metastases is improved
      local control. Our earlier retrospective review identified pattern of enhancement
      on day-of-treatment imaging as a prognostic indicator for freedom from
      progression (FFP) after RS in 219 brain metastases. The current study was
      performed to corroborate this preliminary finding. METHODS AND MATERIALS: Records
      and imaging studies of patients treated with RS from 1991 to 1997 were reviewed.
      Each metastasis was categorized as homogeneously-, heterogeneously-, or ring
      enhancing. Kaplan-Meier FFP was calculated from the date of RS to the first
      imaging showing tumor progression. Univariate and multivariate analyses were
      performed using Cox proportional hazard models stratified by primary site and
      type of RS (alone, as a boost, or for recurrence). RESULTS: Of 682 lesions in 258
      patients, 518 lesions in 193 patients were evaluable. Pattern of enhancement was
      homogeneous in 59%, heterogeneous in 32%, and ring-like in 8% of lesions. One
      year FFP probabilities for homogeneously-, heterogeneously-, and ring-enhancing
      lesions were 90% (95% confidence interval, 84-93%), 76% (64-84%), and 57% (35
      74%), respectively. The p-value for pattern of enhancement from the stratified
      multivariate analysis was 0.019 adjusting for RS dose and treatment period (1991
      1994 vs. 1995-1997). Similar results were achieved adjusting for tumor volume
      instead of RS dose. CONCLUSION: Pattern of enhancement is confirmed as a
      significant prognostic factor for FFP of brain metastases treated with RS,
      independent of dose and volume. A possible explanation is radioresistance of
      hypoxic tumor cells associated with necrotic regions, suggesting future
      investigations with radiosensitizers, hypoxic cell sensitizers, or strategies to
      improve tumor oxygenation.

PMID- 11316558
TI  - Calculation of the uncertainty in complication probability for various dose
      response models, applied to the parotid gland.
AB  - PURPOSE: Usually, models that predict normal tissue complication probability
      (NTCP) are fitted to clinical data with the maximum likelihood (ML) method. This
      method inevitably causes a loss of information contained in the data. In this
      study, an alternative method is investigated that calculates the parameter
      probability distribution (PD), and, thus, conserves all information. The PD
      method also allows the calculation of the uncertainty in the NTCP, which is an
      (often-neglected) prerequisite for the intercomparison of both treatment plans
      and NTCP models. The PD and ML methods are applied to parotid gland data, and the
      results are compared. METHODS AND MATERIALS: The drop in salivary flow due to
      radiotherapy was measured in 25 parotid glands of 15 patients. Together with the
      parotid gland dose-volume histograms (DVH), this enabled the calculation of the
      parameter PDs for three different NTCP models (Lyman, relative seriality, and
      critical volume). From these PDs, the NTCP and its uncertainty could be
      calculated for arbitrary parotid gland DVHs. ML parameters and resulting NTCP
      values were calculated also. RESULTS: All models fitted equally well. The
      parameter PDs turned out to have nonnormal shapes and long tails. The NTCP
      predictions of the ML and PD method usually differed considerably, depending on
      the NTCP model and the nature of irradiation. NTCP curves and ML parameters
      suggested a highly parallel organization of the parotid gland. CONCLUSIONS:
      Considering the substantial differences between the NTCP predictions of the ML
      and PD method, the use of the PD method is preferred, because this is the only
      method that takes all information contained in the clinical data into account.
      Furthermore, PD method gives a true measure of the uncertainty in the NTCP.

PMID- 11316559
TI  - Interferon-gamma in 5 patients with cutaneous radiation syndrome after radiation
      therapy.
AB  - BACKGROUND: Irradiation can cause acute inflammatory responses as well as chronic
      fibrotic alterations of the skin. Cutaneous radiation fibrosis evokes a complex
      of therapeutic problems. However, therapeutic options, apart from surgical
      approaches, are limited. PATIENTS AND METHODS: Five female patients suffering
      from severe cutaneous fibrosis were treated with interferon-gamma on a low-dose
      regimen, 3 x 100 microg/week subcutaneously for 6 months, then once per week for
      another 6 months. In 4 patients, skin thickness was measured with high-frequency
      (20 MHz) ultrasound in a clinically well-defined target skin lesion. In 1
      patient, nuclear magnetic resonance imaging was performed to quantify the extent
      of cutaneous radiation fibrosis and to monitor the therapeutic outcome. RESULTS:
      All patients suffered from radiation-induced cutaneous fibrosis. Additionally, in
      1 patient, a fistula, as assessed by lymph vessel scintigraphy, and in another
      patient a radiation ulcer was diagnosed. In all patients, reduction of radiation
      induced fibrosis could be documented. Both fistula and radiation ulcer regressed
      completely under interferon-gamma therapy. CONCLUSION: Low-dose interferon-gamma
      therapy is a new and effective treatment modality for cutaneous radiation
      fibrosis caused by radiation therapy. The positive impact of interferon-gamma on
      our patients warrants randomized double-blind trials on therapy of radiation
      fibrosis.

PMID- 11316560
TI  - Treatment of keloids by high-dose-rate brachytherapy: A seven-year study.
AB  - PURPOSE: To analyze the results obtained in a prospective group of patients with
      keloid scars treated by high-dose-rate (HDR) brachytherapy with or without
      surgery. METHODS AND MATERIALS: One hundred and sixty-nine patients with keloid
      scars were treated with HDR brachytherapy between December 1991 and December
      1998. One hundred and thirty-four patients were females, and 35 were males. The
      distribution of keloid scars was as follows: face, 77; trunk, 73; and
      extremities, 19. The mean length was 4.2 cm (range 2-22 cm), and the mean width
      1.8 cm (range 1.0-2.8 cm). In 147 patients keloid tissues were removed before HDR
      brachytherapy treatment, and in 22 HDR brachytherapy was used as definitive
      treatment. In patients who underwent prior surgery, a flexible plastic tube was
      put in place during the surgical procedure. Bottoms were used to fix the plastic
      tubes, and the surgical wound was repaired by absorbable suture. HDR
      brachytherapy was administered within 30-60 min of surgery. A total dose of 12 Gy
      (at 1 cm from the center of the catheter) was given in four fractions of 300 cGy
      in 24 h (at 09.00 am, 15.00 pm, 21.00 pm, and 09.00 am next day). Treatment was
      optimized using standard geometric optimization. In patients who did not undergo
      surgery, standard brachytherapy was performed, and plastic tubes were placed
      through the skin to cover the whole scar. Local anesthesia was used in all
      procedures. In these patients a total dose of 18 Gy was given in 6 fractions of
      300 cGy in one and a half days (at 9.00 am, 3.00 pm, and 9.00 pm; and at 9.00 am,
      3.00 pm, and 9.00 pm next day). No further treatment was given to any patient.
      Patients were seen in follow-up visits every 3 months during the first year,
      every 6 months in the second year, and yearly thereafter. No patient was lost to
      follow-up. Particular attention was paid to keloid recurrence, late skin effects,
      and cosmetic results. RESULTS: All patients completed the treatment. After a
      follow-up of seven years, 8 patients (4.7%) had keloid recurrences. Five of these
      had undergone prior surgery (local failure rate 3.4%), and 3 had received only
      HDR brachytherapy (local persistence rate 13.6%). Cosmetic results were
      considered to be good or excellent in 130/147 patients treated with prior surgery
      and in 17/22 patients without surgery. Skin pigmentation changes were observed in
      10 patients, and telangiectasias in 12 patients. No late effects such as skin
      atrophy or skin fibrosis were observed during the 7 years of follow-up.
      CONCLUSIONS: HDR brachytherapy is an effective treatment for keloid scars. It is
      well tolerated and does not present significant side effects. The brachytherapy
      results were more successful in patients who underwent previous surgical excision
      of keloid scar than in patients without surgery. We favor HDR brachytherapy
      rather than superficial X-rays or low energy electron beams in keloid scars,
      because HDR provides a better selective deposit of radiation in tissues and a
      lower degree of normal tissue irradiation. Other advantages of high-dose-rate
      brachytherapy over low-dose-rate brachytherapy are its low cost, the fact that it
      can be performed on an outpatient basis, its excellent radiation protection, and
      the better dose distribution obtained. From the clinical perspective, the
      technique provides a high local control rate without significant sequelae or
      complications.

PMID- 11316561
TI  - Initial employment experiences of 1997 graduates of radiation oncology training
      programs.
AB  - PURPOSE: To inform the profession of current trends in the job market, the
      American College of Radiology (ACR) sought to detail the job-hunting experiences
      and outcomes of 1997 graduates of radiation oncology training programs. METHODS
      AND MATERIALS: In early 1998, questionnaires were mailed to all graduates; 67%
      responded. Results were compared with similar surveys of 1996 graduates. RESULTS:
      Similar to past years, immediately after graduation, 13% of residency graduates
      and 1 of 10 fellowship graduates encountered serious employment difficulties-
      that is, spent some time working locums, working outside radiation oncology, or
      unemployed. By 6-12 months after graduation, approximately 2% of all residency
      graduates were working outside the profession and approximately 3% were not
      working at all. Eighty-five percent of residency graduates and 7 of 8 fellowship
      graduates reported that their employment reasonably matched their training and
      individual goals. On average, graduates' actual salaries approximately
      corresponded to expected salaries. Eleven percent of all graduates were in
      nonownership-track jobs, a significant decline since 1996. For residents and
      fellows combined, 46% had a job with at least one characteristic some observers
      associate with a weak job market, but fewer than half of those with one of these
      characteristics actually disliked it. These percentages are similar to 1996.
      Women graduates were more likely than men to have spouse-related restrictions on
      job location but less likely to end up in a self-reportedly undesirable location.
      CONCLUSION: Unemployment remained low. Some other indicators of the employment
      market showed improvement, while others did not.

PMID- 11316562
TI  - Skin markings in external radiotherapy by temporary tattooing with henna:
      improvement of accuracy and increased patient comfort.
AB  - PURPOSE: To guarantee invariable skin markings in patients undergoing a course of
      external radiotherapy, especially using conformal techniques. Cutaneous markings
      with henna also increase patient comfort, because washing and showering are
      allowed. METHODS AND MATERIALS: Henna, a completely natural product, is a skin
      colorant with a history of 5,000 years. It is applied to the skin in the form of
      a paste. While drying, henna stains the superficial skin layers for several
      weeks, and the marked area can be exposed to water arbitrarily. In case of fading
      of the stain before the end of radiotherapy, the marking procedure can be
      repeated. From November 1998 until March 2000, we performed skin markings with
      henna in 158 patients with different tumor sites. The majority of patients
      received conformal radiotherapy techniques. All patients have been evaluated
      concerning durability of the markings, the RESULTS: The median durability of
      henna staining is 23 days (range 12-48 days). On average, two marking procedures
      (range 1-4) are necessary for a patient treated with curative intent. Although
      washing and showering are freely permitted, no adverse cutaneous side effects
      (e.g., erythema, allergic reactions) have been observed. CONCLUSIONS: Skin
      marking by temporary tattooing with henna increases the accuracy of external
      radiotherapy. It yields stable and invariable markings for the entire course of
      radiotherapy and also increases the comfort of patients.

PMID- 11316563
TI  - Enhancement of radiosensitivity by proteasome inhibition: implications for a role
      of NF-kappaB.
AB  - PURPOSE: NF-kappaB is activated by tumor necrosis factor, certain
      chemotherapeutic agents, and ionizing radiation, leading to inhibition of
      apoptosis. NF-kappaB activation is regulated by phosphorylation of IkappaB
      inhibitor molecules that are subsequently targeted for degradation by the
      ubiquitin-proteasome pathway. PS-341 is a specific and selective inhibitor of the
      proteasome that inhibits NF-kappaB activation and enhances cytotoxic effects of
      chemotherapy in vitro and in vivo. The objective of this study was to determine
      if proteasome inhibition leads to enhanced radiation sensitivity. METHODS AND
      MATERIALS: Inhibition of NF-kappaB activation in colorectal cancer cells was
      performed by treatment of LOVO cells with PS-341 or infection with an adenovirus
      encoding IkappaB super-repressor, a selective NF-kappaB inhibitor. Cells were
      irradiated at 0, 2, 4, 6, 8, and 10 Gy with or without inhibition of NF-kappaB.
      NF-kappaB activation was determined by electrophoretic mobility gel shift assay,
      and apoptosis was evaluated using the TUNEL assay. Growth and clonogenic survival
      data were obtained to assess effects of treatment on radiosensitization. In vitro
      results were tested in vivo using a LOVO xenograft model. RESULTS: NF-kappaB
      activation was induced by radiation and inhibited by pretreatment with either PS
      341 or IkappaBalpha super-repressor in all cell lines. Inhibition of radiation
      induced NF-kappaB activation resulted in increased apoptosis and decreased cell
      growth and clonogenic survival. A 7-41% increase in radiosensitivity was observed
      for cells treated with PS-341 or IkappaBalpha. An 84% reduction in initial tumor
      volume was obtained in LOVO xenografts receiving radiation and PS-341.
      CONCLUSIONS: Inhibition of NF-kappaB activation increases radiation-induced
      apoptosis and enhances radiosensitivity in colorectal cancer cells in vitro and
      in vivo. Results are encouraging for the use of PS-341 as a radiosensitizing
      agent in the treatment of colorectal cancer.

PMID- 11316564
TI  - Genistein, a tyrosine kinase inhibitor, enhanced radiosensitivity in human
      esophageal cancer cell lines in vitro: possible involvement of inhibition of
      survival signal transduction pathways.
AB  - PURPOSE: The effect of genistein, a tyrosine kinase inhibitor, on
      radiosensitivity was examined, especially focusing on "survival signal
      transduction pathways." METHODS AND MATERIALS: Two human esophageal squamous cell
      cancer cell lines, TE-1 (p53, mutant) and TE-2 (p53, wild), were used.
      Radiosensitivity was determined by clonogenic assay, and activation of survival
      signals was examined by Western blot. RESULTS: Genistein (30 microM) greatly
      enhanced radiosensitivity in these cell lines by suppressing radiation-induced
      activation of survival signals, p42/p44 extracellular signal-regulated kinase and
      AKT/PKB. Significant increase in the percentage of apoptotic cells and increased
      poly[ADP-ribose] polymerase cleavage were observed in TE-2, but not in TE-1 even
      after combination of genistein with irradiation. In terms of changes in
      expression of p53-related proteins, increase in expression of Bax and decrease in
      that of Bcl-2 were observed in TE-2 but not in TE-1, suggesting that the main
      mode of cell death induced by genistein in a cell line with wild type p53
      differed from that with mutant p53. CONCLUSIONS: This study suggested that
      survival signals, including p42/p44 ERK and AKT/PKB, may be involved in
      determining radiosensitivity, and genistein would be a potent therapeutic agent
      that has an enhancing effect on radiation.

PMID- 11316565
TI  - Differential expression of growth factors in irradiated mouse testes.
AB  - PURPOSE: By using as an experimental model the male mouse gonad, which contains
      both radiosensitive (germ) and radioresistant (somatic) cells, we have studied
      the growth factor (and/or receptor) expression of transforming growth factor-beta
      receptor (TGFbeta RI), stem cell factor (SCF), c-kit, Fas-L, Fas, tumor necrosis
      factor receptor (TNF R55), and leukemia inhibiting factor receptor (LIF-R) after
      local irradiation. METHODS AND MATERIALS: Adult male mice were locally irradiated
      on the testes. Induction of apoptosis in the different testicular cell types
      following X-ray radiation was identified by the TdT-mediated dUTP Nick End
      Labeling (TUNEL) approach. Growth factor expression was evidenced by
      semiquantitative RT-PCR and Western blot analyses. RESULTS: Apoptosis, identified
      through the TUNEL approach, occurred in radiosensitive testicular (premeotic)
      germ cells with the following kinetics: the number of apoptotic cells increased
      after 24 h (p < 0.001) and was maximal 48 h after a 2-Gy ionizing radiation (p <
      0.001). Apoptotic cells were no longer observed 72 h after a 2-Gy irradiation.
      The number of apoptotic cells increased with the dose of irradiation (1-4 Gy). In
      the seminiferous tubules, the growth factor expression in premeiotic
      radiosensitive germ cells was modulated by irradiation. Indeed Fas, c-kit, and
      LIF-R expression, which occurs in (radiosensitive) germ cells, decreased 24 h
      after a 2-Gy irradiation, and the maximal decrease was observed with a 4-Gy
      irradiation. The decrease in Stra8 expression occurred earlier, at 4 h after a 2
      Gy irradiation. In addition, a significant (p < 0.03) decrease in Stra8 mRNA
      levels was observed at the lowest dose used (0.5 Gy, 48 h). Moreover, concerning
      a growth factor receptor, such as TGFbeta RI, which is expressed both in
      radiosensitive and radioresistant cells, we observed a differential expression
      depending on the cell radiosensitivity after irradiation. Indeed, TGFbeta RI
      expression was increased after irradiation in interstitial radioresistant
      testicular cells in a dose- and time-dependent manner, while it decreased in
      seminiferous radiosensitive (germ cells) testicular cells. Such a differential
      expression between radioresistant and radiosensitive cells in TGFbeta RI levels
      was observed in terms of both mRNA and protein. In contrast, the growth factors
      specifically expressed in the somatic radioresistant (Sertoli) cells in the
      seminiferous tubules (SCF, Fas-L, TNF R55) were not affected by ionizing
      radiation (up to 4 Gy, 72 h). CONCLUSION: Growth factor expression decreased in
      the radiosensitive testicular cells after irradiation. Such a decrease occurred
      before the detection of apoptosis using the TUNEL approach. TGFbeta RI mRNA
      levels decreased in the radiosensitive cells, whereas it increased in the
      radioresistant cells, suggesting that TGFbeta RI may represent a biomarker of the
      intrinsic radiosensitivity of cells.

PMID- 11316566
TI  - Effect of ionizing radiation on thymidine uptake, differentiation, and VEGFR2
      receptor expression in endothelial cells: the role of VEGF(165).
AB  - PURPOSE: Late thrombosis of irradiated vascular segments may be the consequence
      of endothelial cell (EC) dysfunction after radiation therapy. We investigated the
      effects of beta ionizing radiation on human EC viability, thymidine uptake, and
      differentiation. METHODS AND MATERIALS: Endothelial cells were exposed to (32)P
      labeled DNA oligonucleotides in incremental doses of 2, 6, and 10 Gy. The
      modulation of the VEGFR2 receptor expression after irradiation and the overall
      potential radioprotective effect of VEGF(165) on these functions were assayed.
      RESULTS: A dose-dependent inhibitory effect of beta irradiation on ECs' thymidine
      uptake and differentiation was observed. EC viability, however, was not affected
      at levels of radiation up to 10 Gy. VEGF(165) proved to have a radioprotective
      effect as ECs' thymidine uptake, after radiation doses of 2, 6, and 10 Gy, was
      increased by 1.5-, 2-, and 4-fold, respectively, in the presence of 10 ng/ml of
      VEGF(165) (p < 0.05 vs. LacZ). This concentration of VEGF(165) also proved
      beneficial in maintaining cell differentiation at 16 h postirradiation when
      compared to controls. These biologic effects were in direct correlation with the
      upregulation of VEGFR2 receptor expression in irradiated ECs. CONCLUSIONS: beta
      irradiation interacts directly with EC functions by significantly reducing their
      ability to differentiate and proliferate, associated with upregulation of VEGFR2.
      These effects can be prevented in part by pretreating cells with VEGF(165), an
      effect potentially favored by the upregulation of VEGFR2 receptor expression
      after irradiation.

PMID- 11316567
TI  - Cell cycle and growth response of CHO cells to X-irradiation: threshold-free
      repair at low doses.
AB  - PURPOSE: To test the hypothesis of a threshold for induced repair of DNA damage
      (IR) and, secondarily, of hyperradiosensitivity (HRS) to low-dose X-irradiation.
      METHODS AND MATERIALS: Exponentially growing Chinese hamster ovary cells (CHO)
      were X-irradiated with doses from 0.2 to 8 Gy. Survival data were established by
      conventional colony-forming assay and flow-cytometric population counting. The
      early cell cycle response to radiation was studied based on DNA-profiles and
      bromodeoxyuridine pulse-labeling experiments. RESULTS: Colony-forming data were
      consistent with HRS. However, these data were of low statistic significance.
      Population counting provided highly reproducible survival curves that were in
      perfect accord with the linear-quadratic (LQ) model. The dominant cell cycle
      reaction was a dose-dependent delay of G2 M and late S-phase. CONCLUSION: There
      was no evidence for a threshold of IR and for low-dose HRS in X-irradiated CHO
      cells. It is suggested that DNA damage repair activity is constitutively
      expressed during S-phase and is additionally induced in a dose-dependent and
      threshold-free manner in late S-phase and G2. The resulting survival is precisely
      described by the LQ model.

PMID- 11316568
TI  - The influence of autologous tumor fibroblasts on the radiosensitivity of squamous
      cell carcinoma megacolonies.
AB  - PURPOSE: To study the influence of tumor fibroblasts on radiosensitivity and stem
      cell fraction of tumor cells in squamous cell carcinoma megacolonies by
      determining colony cure and clonogen survival. METHODS AND MATERIALS: Murine
      squamous cell carcinoma cells (AT478c) grown as flat but multilayered
      megacolonies were co-cultured with pre-irradiated tumor fibroblasts derived from
      the same carcinoma, and irradiated with 1, 2, 4, or 8 fractions. Recurrent clones
      and their growth pattern in situ were recorded. From megacolony cure data and
      clonogen survival data, the clonogen number and the parameters of cellular
      radiosensitivity were calculated. RESULTS: The curability of the co-cultured
      megacolonies, as determined by TCD50 values, was significantly increased compared
      to the megacolonies without fibroblasts (p < 0.01). Both the megacolony cure and
      clonogen survival data suggested a decrease of the clonogen fraction in the co
      cultured megacolonies. CONCLUSIONS: The presence of tumor fibroblasts increases
      megacolony radiosensitivity. This is due to a decrease in the fraction of
      clonogens in the tumor megacolony, apparently caused by a downregulation of the
      stem cell fraction of the tumor cells.

PMID- 11316569
TI  - Room shielding for intensity-modulated radiation therapy treatment facilities.
AB  - PURPOSE: The traditional assumptions used in room-shielding calculations are
      reassessed for intensity-modulated radiation therapy (IMRT). IMRT makes
      relatively inefficient use of monitor units (MUs) when compared to conventional
      radiation therapy, affecting the assumptions used in room-shielding calculations.
      For the same single-fraction tumor dose delivered, the total number of MUs for
      IMRT is much greater than for a conventional treatment. Therefore, the exposure
      contribution from the linear accelerator head leakage will be significantly
      greater than with conventional treatments. METHODS AND MATERIALS: We propose a
      shielding calculation model that decouples the concepts of workload, MUs, and
      target dose when determining primary and secondary barrier thicknesses. The
      workload for primary barrier calculations for conventional multileaf collimator
      (MLC) IMRT treatments is determined according to patient tumor doses. The same
      calculation for accelerator-based serial tomotherapy IMRT requires scaling by the
      average number of treatment slices. However, rotational therapy yields a small
      use factor that compensates for this increase. We further define a series of
      efficiency factors to account for the small field sizes employed in IMRT. For
      secondary barrier calculations, the patient-scattered radiation is assumed to be
      the same for all IMRT modalities as for conventional therapy. The accelerator
      head leakage contribution is proportional to the number of MUs. Knowledge of the
      average number of MUs per patient is required to estimate the head leakage
      contribution. We used a 6-MV linear accelerator photon beam to guide the
      development of this technique and to evaluate the adequacy of conventional
      barriers for IMRT. Average weekly IMRT workload estimates were made based on our
      experience with 180 serial tomotherapy patients and published data for both "step
      and shoot" and dynamic MLC delivered treatments. RESULTS: We found that
      conventional primary barriers are adequate for both dynamic MLC and serial
      tomotherapy IMRT. However, the excessive head leakage produced by these
      modalities requires an increase in secondary barrier shielding. CONCLUSION: When
      designing shielding for an IMRT facility, increases in accelerator head leakage
      must be taken into account for secondary shielding. Adequacy of secondary
      shielding will depend on the IMRT patient load. For conventional facilities that
      are being assessed for IMRT therapy, existing primary barriers will typically
      prove adequate.

PMID- 11316570
TI  - 3D reconstruction of the encapsulating contour of arteriovenous malformations for
      radiosurgery using digital subtraction angiography.
AB  - PURPOSE: Treatment planning for radiosurgery depends on the precise definition of
      radiation target volumes. For vascular pathologies such as arteriovenous
      malformations (AVM), the most usual technique remains standard X-ray projection
      imaging, most often carried out under stereotactic conditions. To further benefit
      from the advantages of two-dimensional digital subtraction angiography (DSA), the
      authors have developed a method for determining the three-dimensional shape of
      arteriovenous malformations from two views. METHODS AND MATERIALS: After
      correction of image intensifier distortion and calibration of both views, the 3D
      shape of the AVM was determined from two DSA projections using epipolarity
      geometry. The AVM-encapsulating contour was modeled by triangulation of a stack
      of almost parallel ellipses. The method was technically validated using
      artificial targets in a skull phantom. Clinical validation was carried out on 10
      patients who were examined using both conventional angiography under stereotactic
      conditions (SX-ray) and DSA. RESULTS: There was excellent agreement between the
      artificial target volumes measured with SX-ray and with DSA. The correspondence
      between AVM volumes found for patients was not as good as with the phantom.
      CONCLUSIONS: The different image characteristics of the two modalities lead to
      some differences in AVM estimations. However, the results were sufficiently
      satisfactory to justify routine use of this AVM modeling technique for
      radiosurgery planning.

PMID- 11316571
TI  - Standardization of prostate brachytherapy treatment plans.
AB  - PURPOSE: Whereas custom-designed plans are the norm for prostate brachytherapy,
      the relationship between linear prostate dimensions and volume calls into
      question the routine need for customized treatment planning. With the goal of
      streamlining the treatment-planning process, we have compared the treatment
      margins (TMs) achieved with one standard plan applied to patients with a wide
      range of prostate volumes. METHODS AND MATERIALS: Preimplant transrectal
      ultrasound (TRUS) images of 50 unselected University of Washington patients with
      T1-T2 cancer and a prostate volume between 20 cc and 50 cc were studied. Patients
      were arbitrarily grouped into categories of 20-30 cc, 30-40 cc, and 40-50 cc. A
      standard 19-needle plan was devised for patients in the 30- to 40-cc range, using
      an arbitrary minimum margin of 5 mm around the gross tumor volume (GTV), making
      use of inverse planning technology to achieve 100% coverage of the target volume
      with accentuation of dose at the periphery and sparing of the central region. The
      idealized plan was applied to each patient's TRUS study. The distances (TMs)
      between the prostatic edge (GTV) and treated volume (TV) were determined
      perpendicular to the prostatic margin. RESULTS: Averaged over the entire patient
      group, the ratio of thickness to width was 1.4, whereas the ratio of length to
      width was 1.3. These values were fairly constant over the range of volumes,
      emphasizing that the prostate retains its general shape as volume increases. The
      idealized standard plan was overlaid on the ultrasound images of the 17 patients
      in the 30- to 40-cc group and the V100, the percentage of target volume receiving
      100% or more of the prescription dose, was 98% or greater for 15 of the 17
      patients. The lateral and posterior TMs fell within a narrow range, most being
      within 2 mm of the idealized 5-mm TM. To estimate whether a 10-cc volume-interval
      stratification was reasonable, the standard plan generated from the 30- to 40-cc
      prostate model was applied to 5 patients each from the 20- to 30-cc group and the
      40- to 50-cc group. Using the standard plan designed for the 30- to 40-cc group,
      the TMs were closer to 10 mm than to 5 mm for the smaller volume glands and too
      small for the larger volume ones, assuming an ideal margin of 5 mm. CONCLUSION:
      The application of standardized plans to prostate brachytherapy is feasible.
      Stratifying the volume in 10-cc intervals appears to be adequate, suggesting that
      the majority of cases appropriate for treatment with brachytherapy might be
      treated with three standard plans. While the authors believe that the use of a
      limited number of standard treatment plans is feasible, practical, and medically
      acceptable, it should be emphasized that the use of a standard plan should always
      be previewed by computer-aided application to the particular patient's planning
      images.

PMID- 11316572
TI  - Organ motion and its management.
AB  - PURPOSE: To compile and review data on the topic of organ motion and its
      management. METHODS AND MATERIALS: Data were classified into three categories:
      (a) patient position-related organ motion, (b) interfraction organ motion, and
      (c) intrafraction organ motion. Data on interfraction motion of gynecological
      tumors, the prostate, bladder, and rectum are reviewed. Literature pertaining to
      the intrafraction movement of the liver, diaphragm, kidneys, pancreas, lung
      tumors, and prostate is compiled. Methods for managing interfraction and
      intrafraction organ motion in radiation therapy are also reviewed.

PMID- 11316574
TI  - DNA breakage induced by 1,2,4-benzenetriol: relative contributions of oxygen
      derived active species and transition metal ions.
AB  - We report here the relative roles of metals and selected reactive oxygen species
      in DNA damage by the genotoxic benzene metabolite 1,2,4-benzenetriol, and the
      interactions of antioxidants in affording protection. 1,2,4-Benzenetriol induces
      scission in supercoiled phage DNA in neutral aqueous solution with an effective
      dose (ED(50)) of 6.7 microM for 50% cleavage of 2.05 microg/ml supercoiled PM2
      DNA. In decreasing order of effectiveness: catalase (20 U/ml), formate (25 mM),
      superoxide dismutase (20 U/ml), and mannitol (50 mM) protected, from 85 to 28%.
      Evidently, H(2)O(2) is the dominant active species, with O(2)(*)(-) and *OH
      playing subordinate roles. Desferrioxamine or EDTA inhibited DNA breakage by 81
      85%, despite accelerating 1,2,4-benzenetriol autoxidation. Consistent with this
      suggestion of a crucial role for metals, addition of cupric, cuprous, ferric, or
      ferrous ions enhanced DNA breakage, with copper being more active than iron.
      Combinations of scavengers protected more effectively than any single scavenger
      alone, with implications for antioxidants acting in concert in living cells.
      Synergistic combinations were superoxide dismutase with *OH scavengers,
      superoxide dismutase with desferrioxamine, and catalase with desferrioxamine.
      Antagonistic (preemptive) combinations were catalase with superoxide dismutase,
      desferrioxamine with *OH scavengers, and catalase with *OH scavengers. The most
      striking aspect of synergism was the extent to which metal chelation
      (desferrioxamine) acted synergistically with either catalase or superoxide
      dismutase to provide virtually complete protection. Concluding, 1,2,4
      benzenetriol-induced DNA damage occurs mainly by site-specific, Fenton-type
      mechanisms, involving synergism between several reactive intermediates. Multiple
      antioxidant actions are needed for effective protection.

PMID- 11316575
TI  - Acidic fibroblast growth factor (FGF-1) signaling inhibits peroxynitrite-induced
      cell death during pancreatic tumorigenesis.
AB  - Previous immunohistochemical studies have demonstrated enhanced appearance of FGF
      1 and nitrotyrosine, a footprint of reactive nitrogen species peroxynitrite
      (ONOO(-)), in human pancreatic adenocarcinoma. We have examined the consequences
      of constitutive exposure to FGF-1 in nontumorigenic rat ductal epithelial cells
      (ARIP). ARIP cells were transduced with either a secreted chimera of FGF-1,
      ARIP(FGF-1), or a control plasmid, 65 RIP(betag). These cells were evaluated for
      alteration in growth and morphology, responses to ONOO(-) (protein tyrosine
      nitration/phosphorylation), and in vivo tumor formation. ARIP(FGF-1) cells, in
      contrast to 65 RIP(betag), demonstrated a transformed morphology, a 2-fold
      increased growth rate, and enhanced protein tyrosine phosphorylation. Treatment
      with 150 microM ONOO(-) resulted in 86 and 7% (p <.01) death of ARIP(betag) and
      ARIP(FGF-1), respectively. Exposure of 65 RIP(betag) cells to ONOO(-) enhanced
      tyrosine phosphorylation and tyrosine nitration of several polypeptides. Cell
      signaling by FGF-1 enhanced both phosphorylation and nitration of tyrosine
      residues in target proteins modified by ONOO(-). ARIP(betag) cells failed to
      exhibit tumor formation in nude mice, but at d 7 in vivo cells were TUNEL and
      nitrotyrosine positive and FGF-1 negative. ARIP(FGF-1) cells readily formed tumor
      nodules, exhibiting features of pancreatic adenocarcinoma and demonstrating FGF-1
      positive, nitrotyrosine-positive, and TUNEL-negative epithelium. These results
      suggest an interdependent role between FGF-1 and ONOO(-) during the development
      and progression of pancreatic adenocarcinoma.

PMID- 11316576
TI  - A catechol antioxidant protocatechuic acid potentiates inflammatory leukocyte
      derived oxidative stress in mouse skin via a tyrosinase bioactivation pathway.
AB  - The modifying effects of topical application of a catechol antioxidant
      protocatechuic acid (PA) on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced
      inflammatory responses in mouse skin were investigated. Treatment with a high
      dose (20,000 nmol) of PA, based on time of application, modifies inflammatory
      responses in the skin of the B6C3F(1) mouse, a resistant strain to inflammatory
      response induction by TPA, but shows much higher tyrosinase expression than that
      of an albino mouse. The responsibility of a large amount of PA-induced leukocyte
      infiltration to an inflamed region in a B6C3F(1) mouse is more sensitive than
      that of an ICR albino mouse. When ICR mice were treated with TPA (1.6 nmol) twice
      weekly for 5 weeks to induce chronic inflammatory responses, pretreatment with
      1600 nmol PA 30 min prior to each TPA treatment significantly enhanced the
      inflammatory responses including edema formation, leukocyte infiltration, and the
      level of thiobarbituric acid-reacting substances. The dose-dependency was closely
      parallel to the results of a tumor promotion study of PA previously reported.
      Further, the treatment of PA alone resulted in tyrosinase-dependent contact
      hypersensitivity in ICR mouse skin. In addition, the in vitro study of
      cytotoxicity demonstrated that bioactivation by tyrosinase but not
      myeloperoxidase of PA significantly enhanced cytotoxicity and intracellular
      glutathione consumption. We conclude that the tyrosinase-derived reactive quinone
      intermediate(s) of PA, which binds nucleophilic residues of proteins including
      sulfhydryl group and conjugates of which are recognized as haptens, was partially
      involved in alteration of the cellular immune functions including oxygen radical
      generating leukocytes migration to inflamed regions.

PMID- 11316577
TI  - Measurement of free radical production by in vivo microdialysis during
      ischemia/reperfusion injury to skeletal muscle.
AB  - Microdialysis techniques have been used to detect hydroxyl radical and superoxide
      release into the interstitial space of anaesthetized rat anterior tibialis
      muscles during a period of prolonged (4 h) limb ischemia and subsequent
      reperfusion. Data indicate that reperfusion of the ischemic skeletal muscle was
      associated with a large increase in hydroxyl radical activity in the interstitial
      space, which may contribute to the significant oxidation of muscle glutathione,
      protein thiols, and lipids also seen in this model. No evidence for release of
      superoxide into the interstitial space was found during reperfusion, although
      this was observed during electrically stimulated contractile activity of the rat
      limb muscle. These data imply that therapeutic approaches aimed at reduction of
      hydroxyl radical generation in the interstitial fluid are more likely to be
      beneficial in reduction of skeletal muscle reperfusion injury than approaches
      designed to scavenge superoxide radicals.

PMID- 11316578
TI  - Peroxynitrite inhibits inducible (type 2) nitric oxide synthase in murine lung
      epithelial cells in vitro.
AB  - Peroxynitrite, formed by nitric oxide (NO) and superoxide, can alter protein
      function by nitrating amino acids such as tyrosine, cysteine, trytophan, or
      methionine. Inducible nitric oxide synthase (Type 2 NOS or iNOS) converts
      arginine to citrulline, releasing NO. We hypothesized that peroxynitrite could
      function as a negative feedback modulator of NO production by nitration of iNOS.
      Confluent cultures of the murine lung epithelial cell line, LA-4 were stimulated
      with cytokines to express iNOS, peroxynitrite was added, and the flasks sealed.
      After 3 h, NO in the headspace above the culture was sampled. Peroxynitrite
      caused a concentration-dependent decrease in NO. Similar results were obtained
      when 3-morpholinosydnonimine (SIN-1), a peroxynitrite generator, was added to the
      flasks. PAPA-NONOate, the NO generator, did not affect the headspace NO.
      Nitration of the iNOS was confirmed by detection of 3-nitrotyrosine by Western
      blotting. These data suggest a mechanism for inhibition of NO synthesis at
      inflammatory sites where iNOS, NO, and superoxide would be expected.

PMID- 11316579
TI  - Protection by thiols of the mitochondrial complexes from 4-hydroxy-2-nonenal.
AB  - In the present study, the effects of 4-hydroxy-2-nonenal (HNE) on highly purified
      pyruvate dehydrogenase complex (PDC) and its catalytic components in vitro and on
      PDC, alpha-ketoglutarate dehydrogenase complex (KGDC), and the branched-chain
      alpha-keto acid dehydrogenase complex (BCKDC) activities in cultured human HepG2
      cells were investigated. Among the PDC components, the activity of the
      dihydrolipoamide acetyltransferase-E3-binding protein subcomplex (E2-E3BP) only
      was decreased by HNE. Dihydrolipoamide dehydrogenase (E3) protected the E2-E3BP
      subcomplex from HNE inactivation in the absence of the substrates. In the
      presence of E3 and NADH, when lipoyl groups were reduced, higher inactivation of
      the E2-E3BP subcomplex by HNE was observed. Purified PDC was protected from HNE
      induced inactivation by several thiol compounds including lipoic acid plus [LA
      plus; 2-(N,N-dimethylamine)ethylamidolipoate(.)HCl]. Treatment of cultured HepG2
      cells with HNE resulted in a significant reduction of PDC and KGDC activities,
      whereas BCKDC activity decreased to a lesser extent. Lipoyl compounds afforded
      protection from HNE-induced inhibition of PDC. This protection was higher in the
      presence of cysteine and reduced glutathione. Cysteine was able to restore PDC
      activity to some extent after HNE treatment. These findings show that thiols,
      including lipoic acid, provide protection against HNE-induced inactivation of
      lipoyl-containing complexes in the mitochondria.

PMID- 11316580
TI  - beta-carotene at high concentrations induces apoptosis by enhancing oxy-radical
      production in human adenocarcinoma cells.
AB  - This is the first report demonstrating a relationship between apoptosis induction
      and changes of intracellular redox potential in the growth-inhibitory effects of
      high concentrations of beta-carotene in a tumor cell line. beta-Carotene
      inhibited the growth of human WiDr colon adenocarcinoma cells in a dose- and time
      dependent manner, induced apoptosis, and blocked Bcl-2 expression. These effects
      were accompanied by an enhanced production of intracellular reactive oxygen
      species (ROS). The addition of the antioxidant alpha-tocopherol blocked both the
      pro-oxidant and the growth-inhibitory effects of the carotenoid. These findings
      suggest that beta-carotene may act as an inductor of apoptosis by its pro-oxidant
      properties.

PMID- 11316581
TI  - Cellular titration of apoptosis with steady state concentrations of H(2)O(2):
      submicromolar levels of H(2)O(2) induce apoptosis through Fenton chemistry
      independent of the cellular thiol state.
AB  - Apoptosis was studied under conditions that mimic the steady state of H(2)O(2) in
      vivo. This is at variance with previous studies involving a bolus addition of
      H(2)O(2), a procedure that disrupts the cellular homeostasis. The results allowed
      us to define three phases for H(2)O(2)-induced apoptosis in Jurkat T-cells with
      reference to cytosolic steady state concentrations of H(2)O(2) [(H(2)O(2))(ss)]:
      (H(2)O(2))(ss) values below 0.7 microM elicited no effects; (H(2)O(2))(ss)
      approximately 0.7-3 microM induced apoptosis; and (H(2)O(2))(ss) > 3 microM
      yielded no additional apoptosis and a gradual shift towards necrosis as the mode
      of cell death were observed. H(2)O(2)-induced apoptosis was not affected by
      either BCNU, an inhibitor of glutathione reductase, or diamide, a compound that
      reacts both with low-molecular weight and protein thiols, or selenols.
      Glutathione depletion, accomplished by incubating cells either with buthionine
      sulfoximine or in cystine-free medium, rendered cells more sensitive to H(2)O(2)
      induced apoptosis, but did not change the threshold and saturating concentrations
      of H(2)O(2) that induced apoptosis. Two unrelated metal chelators,
      desferrioxamine and dipyridyl, strongly protected against H(2)O(2)-induced
      apoptosis. It may be concluded that, under conditions of H(2)O(2) delivery that
      mimic in vivo situations, the oxidative event that triggers the induction of
      apoptosis by H(2)O(2) is a Fenton-type reaction and is independent of the thiol
      or selenium states of the cell.

PMID- 11316582
TI  - Hepatocellular oxidative DNA injury induced by macrophage-derived nitric oxide.
AB  - Previous studies have indicated that splenic macrophages migrate into the liver
      and play a role in endotoxin-induced hepatic damage. The present study was
      designed to elucidate the mechanisms of hepatocyte injury induced by activated
      splenic macrophages, focusing especially on endogenously released NO and
      oxidative DNA alterations in hepatocytes. Splenic macrophages isolated from
      Wistar rats were incubated with either lipopolysaccharide (LPS) or interferon
      gamma (IFN-gamma) and cocultured with hepatocytes. Nitrite and nitrate levels in
      the culture medium were measured, and inducible-type NO synthase (iNOS) and
      nitrotyrosine were determined by immunofluorescence staining. The ratio of 8
      hydroxy-deoxyguanosine (8-OH-dG) to deoxyguanosine (dG) was measured by high
      performance liquid chromatography, and single-stranded DNA in hepatocytes was
      detected with acridine orange. NO release and nitrotyrosine expression in
      hepatocytes increased after 8 h of coculture with activated macrophages, and this
      coculture also induced increases in the 8-OH-dG/dG ratio and single-stranded DNA
      in the hepatocytes. These alterations were attenuated by superoxide dismutase
      (SOD) and NO synthesis inhibitors. A similar pattern of alterations was observed
      in hepatocytes incubated with SIN-1, and these changes were also prevented by
      SOD. These results suggest that activated macrophage-derived NO and its oxidative
      metabolite, peroxynitrite, play key roles in hepatocyte injury during
      inflammation, and cause subsequent DNA damage in surviving hepatocytes.

PMID- 11316583
TI  - Changes in mitochondrial and microsomal lipid peroxidation and fatty acid
      profiles in adrenal glands, testes, and livers from alpha-tocopherol-deficient
      rats.
AB  - Studies were done to evaluate the effects of alpha-tocopherol deficiency in rats
      on the fatty acid composition and sensitivity to lipid peroxidation (LP) of
      mitochondria and microsomes from adrenal glands, testes, and livers. In control
      (alpha-tocopherol-sufficient) animals, adrenal concentrations of alpha-tocopherol
      were approximately 10 times greater than those in livers and testes. Dietary
      deficiency of alpha-tocopherol for 8 weeks decreased adrenal and hepatic
      concentrations by 80-90% and testicular concentrations by approximately 60-70%.
      Incubation of testicular or hepatic mitochondria and microsomes from control rats
      with FeSO(4) (1.0 mM) caused a time-dependent stimulation of LP as indicated by
      the formation of thiobarbituric acid reactive substances (TBARS); the rate of
      TBARS production increased in preparations from alpha-tocopherol-deficient
      animals. TBARS formation was not demonstrable in adrenal mitochondria or
      microsomes from alpha-tocopherol sufficient rats, but reached high levels in
      alpha-tocopherol-deficient preparations. The fatty acid composition of
      mitochondria and microsomes was tissue-dependent. In particular, arachidonic acid
      comprised approximately 40% of the total fatty acids in adrenal membranes, but
      only 20-25% in testes and livers. alpha-Tocopherol deficiency increased oleic
      acid concentrations in adrenal and hepatic mitochondria and microsomes but not in
      testes. In all three tissues, linoleic acid concentrations decreased by
      approximately 50%, but arachidonic acid levels were unaffected by alpha
      tocopherol deficiency. The results indicate a close relationship between tissue
      sensitivity to LP in vitro and alpha-tocopherol concentrations. Nonetheless, any
      oxidative stress in vivo caused by alpha-tocopherol deficiency seems to spare
      arachidonic acid in mitochondria and microsomes but decreases linoleic acid
      concentrations. It is possible that because of the important physiological
      functions of arachidonic acid, metabolic adaptations serve to maintain membrane
      content during periods of oxidative stress.

PMID- 11316584
TI  - Red wine mitigates the postprandial increase of LDL susceptibility to oxidation.
AB  - The aim of the present study was to verify the extent of oxidative stress induced
      by a meal at plasma and LDL level, and to investigate the capacity of red wine to
      counteract this action. In two different sessions, six healthy men ate the same
      test meal consisting of "Milanese" meat and fried potatoes. The meal was taken
      either with 400 ml red wine or with an isocaloric hydroalcoholic solution.
      Oxidative stress at plasma level was estimated through the measure of ascorbic
      acid, alpha-tocopherol, protein SH groups, uric acid, and antioxidant capacity,
      measured before and 1 and 3 h after the meal. The change in the resistance of LDL
      to oxidative modification was taken as an index of exposure to pro-oxidants. The
      susceptibility to Cu(II)-catalyzed oxidation of baseline and postprandial LDL was
      measured as conjugated dienes formation, tryptophan residues, and relative
      electrophoretic mobility. The experimental meal taken with wine provoked a
      significant increase in the total plasma antioxidant capacity and in the plasma
      concentration of alpha-tocopherol and SH groups. Postprandial LDL was more
      susceptible to metal-catalyzed oxidation than the homologous baseline LDL after
      the ethanol meal. On the contrary, postprandial LDL obtained after the wine meal
      was as resistant or more resistant to lipid peroxidation than fasting LDL.

PMID- 11316586
TI  - Invited Papers.

PMID- 11316585
TI  - Hypoxia-ischemia in fetal rabbit brain increases reactive nitrogen species
      production: quantitative estimation of nitrotyrosine.
AB  - Reactive nitrogen species (RNS) cause nitration of protein-bound tyrosine that is
      used as biomarker for detection. We hypothesized that RNS are formed in fetal
      rabbit brain following acute placental insufficiency. Near-term pregnant rabbits
      were randomized to either repetitive uterine ischemia or no ischemia, and fetal
      brains obtained. Only one electrochemical HPLC method (of three tested) was
      successful in detecting brain nitrotyrosine. Protein nitrotyrosine was
      significantly increased following cumulative 40 min ischemia and 20 min
      reperfusion compared to controls. Repetitive hypoxia-ischemia results in the
      increased formation of RNS in near-term fetal brains.

PMID- 11316587
TI  - Oral Papers.

PMID- 11316588
TI  - Poster Papers.

PMID- 11316589
TI  - GFP moves on.

PMID- 11316590
TI  - P53 and PML: new partners in tumor suppression.

PMID- 11316591
TI  - Mice come unstuck.

PMID- 11316592
TI  - Fanconi anemia: join the club!

PMID- 11316593
TI  - The position of Chk1 in cancer research.

PMID- 11316594
TI  - Morbid myristoylation.

PMID- 11316595
TI  - A new BACE is for therapy of Alzheimer's disease.

PMID- 11316596
TI  - Fighting 'tooth, bone and uterus' to elucidate the functions of neuropilin.

PMID- 11316597
TI  - Rethinking centrosome function.

PMID- 11316598
TI  - Designer integrins proving their value.

PMID- 11316608
TI  - The dynein heavy chain: structure, mechanics and evolution.
AB  - The translocation of dynein along microtubules is the basis for a variety of
      essential cellular movements. Despite a general domain organization that is found
      in all the cytoskeletal motors, there are structural features of dynein that set
      it apart from the other motors. These include a track-binding site that is
      located at the tip of a long projection, and six nucleotide-binding modules that
      together form the globular head of dynein. These unique features suggest that
      dynein produces movement by a mechanism that is different from that used by the
      other motors.

PMID- 11316609
TI  - Imaging biochemistry inside cells.
AB  - Proteins provide the building blocks for multicomponent molecular units, or
      pathways, from which higher cellular functions emerge. These units consist of
      either assemblies of physically interacting proteins or dispersed biochemical
      activities connected by rapidly diffusing second messengers, metabolic
      intermediates, ions or other proteins. It will probably remain within the realm
      of genetics to identify the ensemble of proteins that constitute these functional
      units and to establish the first-order connectivity. The dynamics of interactions
      within these protein machines can be assessed in living cells by the application
      of fluorescence spectroscopy on a microscopic level, using fluorescent proteins
      that are introduced within these functional units. Fluorescence is sensitive,
      specific and non-invasive, and the spectroscopic properties of a fluorescent
      probe can be analysed to obtain information on its molecular environment. The
      development and use of sensors based on the genetically encoded variants of green
      fluorescent proteins has facilitated the observation of 'live' biochemistry on a
      microscopic level, with the advantage of preserving the cellular context of
      biochemical connectivity, compartmentalization and spatial organization. Protein
      activities and interactions can be imaged and localized within a single cell,
      allowing correlation with phenomena such as the cell cycle, migration and
      morphogenesis.

PMID- 11316610
TI  - Molecular controls of antigen receptor clustering and autoimmunity.
AB  - Cellular organization of the cytoskeleton, assembly of intracellular signaling
      complexes and movement of membrane receptors into supramolecular activation
      complexes (SMACs) are crucial prerequisites for lymphocyte activation and
      function. Full T-cell activation requires costimulatory signals in addition to
      antigen-mediated signals. Costimulatory signals facilitate T-cell activation by
      inducing SMAC formation, resulting in sustained signal transduction, cell-cycle
      progression and cytokine production. The guanine nucleotide exchange factor Vav1
      and the Wiscott-Aldrich syndrome protein (WASP) regulate the actin cytoskeleton
      in T cells and also regulate SMAC formation. In mice lacking the E3 ubiquitin
      ligase Cbl-b, the Vav-WASP signaling pathway is active in the absence of
      costimulation resulting in deregulated cytoskeletal reorganization, enhanced
      priming and expansion of autoreactive T cells, and the development of
      autoimmunity. This review discusses the role of Cbl-b, Vav and WASP in the
      regulation of SMAC formation and the implications for the maintenance of
      tolerance and the development of autoimmunity.

PMID- 11316611
TI  - The Ste20 group kinases as regulators of MAP kinase cascades.
AB  - Ste20p (sterile 20 protein) is a putative yeast mitogen-activated protein kinase
      kinase kinase kinase (MAP4K) involved in the mating pathway. Its homologs in
      mammals, Drosophila, Caenorhabditis elegans and other organisms make up a large
      emerging group of protein kinases including 28 members in human. The Ste20 group
      kinases are further divided into the p21-activated kinase (PAK) and germinal
      center kinase (GCK) families. They are characterized by the presence of a
      conserved kinase domain and a noncatalytic region of great structural diversity
      that enables the kinases to interact with various signaling molecules and
      regulatory proteins of the cytoskeleton. This review describes the phylogenetic
      relationships of the Ste20 group kinases based on discussions with many
      researchers in this field. With the newly established phylogenetic relationships,
      crucial arguments can be advanced regarding the functions of these kinases as
      upstream activators of the MAPK pathways and possible activity as MAP4Ks. Their
      involvement in apoptosis, morphogenesis and cytoskeletal rearrangements is also
      discussed.

PMID- 11316612
TI  - Profile--Elaine Fuchs interviewed by Rabiya S. Tuna.

PMID- 11316613
TI  - Criteria for success in interventions for Alzheimer's disease.

PMID- 11316614
TI  - The dynamics of depression and disability.

PMID- 11316615
TI  - Depression and disability in late life: directions for future research.
AB  - The author reviews evidence from epidemiologic and clinical studies suggesting a
      reciprocal, potentially spiraling, relationship between depression and disability
      in older adults. The discussion outlines possible methodological and conceptual
      explanations for this evidence and poses avenues for future research. An
      underlying theme is the impact of how disability and depression are measured on
      the nature of empirical evidence and its interpretation. Measures and
      corresponding analytic strategies that capture the complexity of depression,
      disability, and their relationship are expected to lead to the most fruitful
      approaches to reducing the burden of depression and disability in the lives of
      older adults.

PMID- 11316616
TI  - The association of late-life depression and anxiety with physical disability: a
      review of the literature and prospectus for future research.
AB  - Depression and anxiety disorders are associated with excess disability. The
      authors searched the recent geriatric literature for studies associating late
      life depression or anxiety with physical disability. Studies showed depression in
      old age to be an independent risk factor for disability; similarly, disability
      was found to be a risk factor for depression. Anxiety in late life was also found
      to be a risk factor for disability, although not necessarily independently of
      depression. Increased disability due to depression is only partly explained by
      differences in socioeconomic measures, medical conditions, and cognition.
      Physical disability improves with treatment for depression; comparable studies
      have not been done for anxiety. The authors discuss how these findings inform
      current concepts of physical disability and discuss the implications for future
      intervention studies of late-life depression and anxiety disorders.

PMID- 11316617
TI  - Recruitment and retention of elderly patients in clinical trials: issues and
      strategies.
AB  - Clinicians and researchers alike are shifting their focus to elderly patients in
      order to target the most effective treatments for a variety of psychiatric
      conditions. Clinical trials with elderly patients are the necessary because they
      consume the largest number of prescription medications. There are special
      challenges and considerations in designing and conducting clinical studies. The
      authors review the various phases of such research, including recruitment of
      appropriate patients and retention of those enrolled, and they make suggestions,
      using examples from already completed research studies, illustrating the methods
      found to be most successful.

PMID- 11316618
TI  - Survival of hospitalized elderly patients with delirium: a prospective study.
AB  - The authors tested the relationship between clinically diagnosed delirium during
      hospitalization and increased mortality after accounting for pre-hospital
      measures of global cognition, physical functioning, and medical comorbidity.
      Patients (N=102), 53 of which were hospitalized during the course of a year,
      received the Mini-Mental State Exam, Physical Self-Maintenance Scale, Cumulative
      Illness Rating Scale, and 15-item Geriatric Depression Scale. Mortality rates
      were determined at discharge and after 3 years. Patients who developed delirium
      did not differ on pre-hospitalization levels of depression, global cognitive
      performance, physical functioning, or medical comorbidity. Three-year mortality
      in the hospitalized subjects was 75% for delirium patients vs. 51% for control
      patients (risk ratio=2.24). Delirium occurring during hospitalization places
      elderly subjects at long-term risk of mortality. This effect is not accounted for
      by earlier measures of cognitive, functional, or health status.

PMID- 11316619
TI  - Validating the diagnosis of delirium and evaluating its association with
      deterioration over a one-year period.
AB  - The authors probed the associations between clinical diagnoses and independent
      research measures of cognitive, behavioral, and electroencephalographic (EEG)
      changes in hospitalized older patients and investigated the contribution of
      medical illness to deterioration. Patients (N=96; 47 of whom were hospitalized
      during the course of 1 year; 12 diagnosed with delirium) received tests of
      cognitive and physical functioning and the Cumulative Illness Rating Scale,
      specific neuropsychological tests, and a two-channel EEG. Delirium was associated
      with independent measures of cognitive decline and EEG slowing. Hospitalization
      was associated with deterioration in functional status during the year, whether
      or not patients showed delirium. Results suggest that medical illness leading to
      hospitalization can contribute significantly to deterioration in self-care, and,
      when it is associated with delirium, to deterioration in cognitive performance
      and cerebral activity over a period of 1 year.

PMID- 11316620
TI  - Longitudinal study of quality of life in people with advanced Alzheimer's
      disease.
AB  - The authors examined three indicators of health-related quality of life in people
      with advanced Alzheimer's disease ([AD]; N=150): confinement to home, null
      activity, and null positive affect, as reported by patient proxies. Dementia
      severity predicted time-to-onset for all three disease milestones in models that
      controlled for sociodemographic indicators, nursing home status, and death in the
      follow-up period. Patients whose dementia worsened over follow-up were more
      likely to reach each milestone. These outcomes represent key milestones in the
      care of patients; they are sensitive to disease progression, and they are likely
      to be useful for studying treatment in advanced AD.

PMID- 11316621
TI  - Depression and service utilization in elderly primary care patients.
AB  - The authors analyzed the relationship between a provider's diagnosis of
      depression and health services utilization among all elderly patients (N=3,481)
      seen in a primary care practice over 12 months. Of patients with a diagnosis of
      depression, 29.7% were given an antidepressant. Depressed patients had increased
      outpatient resource utilization, including frequency of appointments, number of
      laboratory tests, X-rays and scans, and consultations. This association remained
      significant after controlling for comorbidity. On average, patients who were
      depressed had two more appointments per year. No difference in total cost of
      hospitalization was observed between the two groups. This study also demonstrated
      a higher incidence of nonspecific medical complaints in depressed vs. non
      depressed elderly primary care patients, and all such nonspecific symptoms were
      associated with increased total ambulatory costs, tests and consultations. The
      somatic presentation of depression may contribute to the increased services
      utilization.

PMID- 11316622
TI  - Diagnostic categorization of behavioral and psychological symptoms in dementia.

PMID- 11316623
TI  - Manic reactions to ECT.

PMID- 11316627
TI  - Hyperinflation and the (passive) chest wall.

PMID- 11316628
TI  - Message in a model.

PMID- 11316629
TI  - Using loop gain to assess ventilatory control in obstructive sleep apnea.

PMID- 11316630
TI  - Serotonin. Culprit or promising therapy for obstructive sleep apnea?

PMID- 11316631
TI  - The GOLD standard for chronic obstructive pulmonary disease.

PMID- 11316632
TI  - Ventilating the acutely injured lung.

PMID- 11316633
TI  - Implications for the pregnant patient.

PMID- 11316635
TI  - Patient-ventilator interaction.

PMID- 11316634
TI  - The need for new drugs against tuberculosis. Obstacles, opportunities, and next
      steps.

PMID- 11316636
TI  - Respiratory health in a globalizing world.

PMID- 11316637
TI  - Comparison of physiological and radiological screening for lung volume reduction
      surgery.
AB  - Physiological and radiological criteria are both used to identify candidates for
      LVRS. This study compares the predictive value of these screening techniques
      among patients with homogeneous (Ho) and heterogeneous (He) emphysema.
      Preoperative inspiratory lung conductance (G(Li)) during spontaneous breathing
      and quantitative radioisotope V/Q scan (QVQS) results were available for 48 of 50
      patients undergoing bilateral LVRS for emphysema. Ho disease (n = 21) was defined
      by QVQS as an upper/lower perfusion ratio (ULPR) between 0.75 and1.25. G(Li)
      correlated with 6-mo improvement in FEV(1) (DeltaFEV(1)-6) (r = 0.53, p < 0.001)
      for the entire cohort, and for patients with both Ho (n = 21, r = 0.56, p =
      0.015) and He disease (n = 27, r = 0.46, p = 0.017). ULPR correlated less well
      with DeltaFEV(1)-6 (n = 48, r = -0.38; p = 0.008) for the cohort, and was
      significantly correlated with outcomes only in the subgroup of patients with He
      disease (r = -0.40, p = 0.04). Multivariate regression demonstrated that by
      combining G(Li) and ULPR criteria, 33% of the DeltaFEV(1)-6 response could be
      accounted for. We conclude that both physiological and radiological criteria help
      identify appropriate candidates for LVRS. G(Li) best identifies patients with Ho
      emphysema who may benefit from surgery, but would be excluded on the basis of
      strictly radiological criteria. ULPR helps identify patients with He disease that
      improves with surgery, despite unfavorable G(Li).

PMID- 11316638
TI  - Interpreting improvement in expiratory flows after lung volume reduction surgery
      in terms of flow limitation theory.
AB  - Spirometry and pulmonary mechanics were measured pre- and postoperatively in 37
      patients undergoing bilateral lung volume reduction surgery (LVRS). The relative
      contributions of changes in compliance (CL), recoil pressures (PTLC), small
      airway conductance (Gu), and airway closing pressures (Ptm') to changes in
      expiratory flows were examined with a Taylor series expansion of the Pride-
      Permutt model of flow limitation. The resulting variational expression, deltaVmax
      = GudeltaPel + PeldeltaGu - GudeltaPtm' - Ptm'deltaGu - deltaGudeltaPtm', was
      then used to describe how the peak flow rate (Vmax) depends on preoperative Gu, P
      TLC, Ptm', and on changes (delta) in these parameters after surgery. After LVRS,
      both FEV(1) and Vmax increased significantly ( DeltaFEV(1) = 28 +/- 44%;
      DeltaVmax = 78 +/- 132%), and changes in FEV(1) and Vmax correlated closely (r =
      0.74, p < 0.001). Among responders (DeltaFEV(1) > or = 12%; n = 19; DeltaFEV(1) =
      60 +/- 38%), PTLC increased (8.8 +/- 2.8 to 12.2 +/- 4.7 cm H2O) and the time
      constant for expiration (tau = CL/Gu) decreased (2.67 +/- 0.62 to 2.35 +/- 0.55
      s), while Ptm', CL, and Gu did not change. GudeltaPel, the change in recoil
      weighted by preoperative conductance upstream of the flow-limiting site,
      accounted for 72% of the improvement in Vmax. Among nonresponders ( DeltaFEV(1) =
      -6 +/- 15%, n = 18), tau increased significantly, contributing to a decline in
      FEV(1)/FVC ratio. PeldeltaGu decreased (-0.25 +/- 0.68, p = 0.013), accounting
      for all of the decline in Vmax. This analysis suggests that (1) improvement in
      expiratory flows after LVRS is largely due to increases in recoil pressure; (2)
      large improvements in FEV(1) can occur without changes in Gu or Ptm', arguing
      that LVRS has little effect on airway resistance or closure; and (3) large
      changes in PTLC can occur without changes in CL, supporting arguments of Fessler
      and Permutt (Am J Respir Crit Care Med 1998;157:715-722) that "resizing of the
      lung to chest wall" is the primary mechanism by which LVRS improves lung
      function.

PMID- 11316639
TI  - Effects of emphysema on diaphragm microvascular oxygen pressure.
AB  - Pulmonary emphysema impairs lung and respiratory muscle function leading to
      restricted physical capacity and accelerated morbidity and mortality consequent
      to respiratory muscle failure. In the absence of direct evidence, an O2 supply
      demand imbalance within the diaphragm and other respiratory muscles in emphysema
      has been considered the most likely explanation for this failure. To test this
      hypothesis, we utilized phosphorescence quenching techniques to measure mean
      microvascular PO2 (PO2m) within the medial costal diaphragm of control (C, n =
      10) and emphysematous (E, elastase instilled, n = 7) hamsters. PO2m and mean
      arterial pressure (MAP) were measured in the spontaneously breathing anesthetized
      hamster at inspired O2 percentages of 10, 21, and 100, and across a range of mean
      MAPs from 40 to 115 mm Hg. At each inspired O2, diaphragm PO2m was significantly
      (p < 0.05) lower in E animals (10%: C, 19 +/- 3; E, 9 +/- 2; 21%: C, 32 +/- 2; E,
      21 +/- 2; 100%: C, 60 +/- 8; E, 36 +/- 9 mm Hg). At 21% inspired O2, the PO2m
      decrease was correlated with reduced MAP in both C (r = 0.968) and E (r = 0.976)
      animals. We conclude that diaphragmatic PO2m (and therefore microvascular O2
      content) is decreased in emphysematous hamsters reflecting a greater
      diaphragmatic O2 utilization at rest and a lower O2 extraction reserve. According
      to Fick's law, this lower PO2m will mandate an exaggerated fall in intramyocyte
      PO2, which is expected to accelerate muscle glycogen depletion and consequently
      fatigue. This provides empirical evidence in support of one possible mechanism
      for respiratory muscle failure in emphysema.

PMID- 11316640
TI  - Use of a long-acting inhaled beta2-adrenergic agonist, salmeterol xinafoate, in
      patients with chronic obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) is a condition in which continuous
      bronchodilation may have clinical advantages. This study evaluated salmeterol, a
      beta-agonist bronchodilator with a duration of action substantially longer than
      that of short-acting beta-agonists, compared with ipratropium, an anticholinergic
      bronchodilator, and placebo in patients with COPD. Four hundred and five patients
      with COPD received either salmeterol 42 microg twice daily, ipratropium bromide
      36 microg four times daily, or placebo for 12 wk in this randomized, double
      blind, parallel-group study. Patients were stratified on the basis of
      bronchodilator response to albuterol (> 12% and > 200-ml improvement) and were
      randomized within each stratum. Bronchodilator response was measured over 12 h
      four times during the treatment period. Salmeterol provided similar maximal
      bronchodilatation to ipratropium but had a longer duration of action and a more
      constant bronchodilatory effect with no evidence of bronchodilator tolerance.
      Both active treatments were well tolerated. Salmeterol was an effective
      bronchodilator with a consistent effect over this 12-wk study in patients with
      COPD, including those "unresponsive" to albuterol. The long duration of action of
      salmeterol offers the advantage of twice daily dosing compared with the required
      four times a day dosing with ipratropium.

PMID- 11316641
TI  - Psychopathology in patients with severe asthma is associated with increased
      health care utilization.
AB  - Severe asthma accounts for the majority of health costs for this disease, which
      is mainly related to the treatment of failed control. Several psychosocial
      factors have been associated with poor asthma control, but the question remains
      whether psychiatric disorder in patients with severe asthma predisposes for
      increased health care utilization. In the present study we compared outpatients
      with severe asthma with and without psychological dysfunctioning with respect to
      health care utilization. All patients used high dose inhaled corticosteroids and
      long-acting bronchodilators for more than 1 yr, and had difficult-to-control
      asthma, requiring one or more courses of corticosteroids during the past year or
      maintenance therapy with prednisone. Medical history was taken and health care
      utilization questionnaires were completed. The General Health Questionnaire (GHQ)
      was used to identify psychiatric cases (GHQ-12 score of > or = 6). There were no
      differences between the psychiatric cases (n = 21) and the noncases (n = 77) with
      respect to demographic and objective disease characteristics. However, the
      psychiatric cases had increased odds ratios (OR) for frequent visits to GP (OR =
      5.9), frequent emergency visits (OR = 5.3), frequent exacerbations (OR = 12.4),
      and frequent hospitalizations (OR = 4.8) as compared with the nonpsychiatric
      patients. The present findings suggest that the morbidity and costs of asthma
      might be related to the level of psychological dysfunctioning in patients with
      severe asthma rather than to asthma severity per se, thereby identifying an area
      of potential intervention.

PMID- 11316642
TI  - Increased frequency of Chlamydia pneumoniae antibodies in patients with asthma.
AB  - The worldwide increase in asthma incidences and the impact of the disease on
      public health care have led to new investigations of the cause of the disease.
      Besides well-defined environmental causes, accumulating evidence suggests that
      respiratory tract infections play an important role in the pathogenesis of
      asthma. Among these microorganisms Chlamydia pneumoniae is an intracellular
      pathogen causing persistent infection. Chlamydia pneumoniae infection has been
      discussed as possibly inducing the development of asthma. This study was designed
      to investigate the presence of C. pneumoniae-specific IgG, IgA, and IgM
      antibodies in serum samples of 33 adults with a clinical history of asthma,
      positive methacholine test, and reduced FEV(1). Patients with asthma were
      compared with age-, sex-, and locality-matched control subjects (n = 33). We
      observed no acute infection either in patients with asthma or in control
      subjects, but 63% of all investigated individuals had signs of past infection.
      Chlamydia pneumoniae-specific IgA was detected in 52% of the patients with asthma
      and in 15% of the healthy control subjects (p < 0.01). Serological evidence of
      chronic infection with C. pneumoniae (high IgG [> pr = 1:512] and high IgA [> or
      = 1:40]) was more frequent in patients with asthma (18.2%) compared with control
      subjects (3.0%) (p < 0.01). Our results provide further evidence that chronic
      infection with C. pneumoniae is linked to asthma.

PMID- 11316643
TI  - The relationship between atopic status and IL-10 nasal lavage levels in the acute
      and persistent inflammatory response to upper respiratory tract infection.
AB  - We examined the influence of atopy on virus-induced airway inflammation by
      comparing the nasal response to naturally acquired upper respiratory tract
      infection in atopic and nonatopic subjects by measurement of cytokine, chemokine,
      and mediator levels in nasal lavage from 44 adults (23 atopic) taken during the
      acute and the convalescent phases of the common cold. Nasal aspirates were
      examined for the presence of upper respiratory viruses by RT-PCR. In atopic and
      nonatopic subjects there were increased levels of IL-1beta, IL-6, IL-8, TNF
      alpha, RANTES, sICAM-1, MPO, ECP, IL-10, and IFN-gamma in nasal lavage during the
      acute compared with the convalescent phase (p < 0.001). During the acute phase
      histamine levels were significantly higher in the atopic than in the nonatopic
      subjects (p < 0.05), whereas IL-10 levels were significantly greater in the
      nonatopic than in the atopic subjects (p < 0.05). At convalescence levels of IL
      1beta, IL-6, sICAM-1, ECP, RANTES and albumin were significantly higher in the
      atopic group (p < 0.05). An upper respiratory tract virus was found in 27
      volunteers (61%) during the acute stage and in two volunteers (4%) at
      convalescence. We conclude that virus-induced inflammatory changes within the
      nose are more prolonged in atopic than in nonatopic subjects and that this is
      associated with reduced IL-10 levels in atopic compared with nonatopic subjects
      during the acute phase of upper respiratory tract infection.

PMID- 11316644
TI  - Asthma, rhinitis, and skin test reactivity to aeroallergens in families of
      asthmatic subjects in Anqing, China.
AB  - In industrialized countries with a Western lifestyle, sensitization to perennial
      aeroallergens is strongly associated with asthma, whereas sensitization to
      seasonal aeroallergens is closely related to allergic rhinitis. Little is known,
      however, about the relation between skin test reactivity to aeroallergens and
      either asthma or rhinitis in mainland China. We studied 10,009 members of 2,544
      families in Anqing (China) that were selected on the basis of physician-diagnosed
      asthma in at least two siblings. Generalized estimating equations were employed
      to study the association between skin test reactivity to aeroallergens and either
      asthma or rhinitis. After adjustment for age, sex, intensity of smoking, skin
      test reactivity to other aeroallergens, and household correlations, sensitization
      to dust mite was an independent predictor of both asthma (OR = 1.3, 95% CI = 1.1
      to 1.5, p = 0.008) and rhinitis (OR = 1.3, 95% CI = 1.0 to 1.8, p = 0.04).
      Sensitization to mold was significantly associated with asthma (OR = 1.6, 95% CI
      = 1.1 to 2.3, p = 0.008), and sensitization to silk was an independent predictor
      of rhinitis (OR = 1.5, 95% CI = 1.1 to 2.2, p = 0.02). Although 46.9% of the
      study participants were sensitized to at least one allergen, only 3.5% of study
      subjects reported nasal symptoms consistent with rhinitis. Among asthmatic
      subjects, 6.2% reported nasal symptoms. Whereas sensitization to perennial
      aeroallergens was associated with asthma among families of asthmatic subjects in
      rural China, sensitization to silk was the strongest predictor of rhinitis in
      this population. Our findings also suggest that allergic rhinitis is far less
      common among asthmatic subjects in rural China than in asthmatic subjects in
      industrialized countries with a Western lifestyle.

PMID- 11316645
TI  - Noninvasive measurement of exhaled nitric oxide in a spontaneously breathing
      mouse.
AB  - Nitric oxide (NO) has been detected in the exhaled gas of animals and humans. In
      previous work, investigators have used anesthetized, mechanically ventilated
      animals to obtain exhaled NO (E(NO)) measurements, which has unclear effects on
      the levels of E(NO) and does not allow for repeated analysis of E(NO). We sought
      to measure E(NO) from a single, spontaneously breathing mouse. The mouse was
      placed in a small Plexiglas chamber and allowed to acclimatize before exhaled gas
      was collected for E(NO) analysis. Under optimal operating conditions of flow and
      pressure, the mean concentration of exhaled NO (FE(NO)) of 25 mice was 10.1 +/-
      1.0 ppb. The maximal variation of FE(NO) when repeatedly measured daily in
      individual animals was 2.1 ppb. Administration of L-NAME, a nonselective NOS
      inhibitor, reduced FE(NO) by 51 +/- 6% (p < 0.01). Intraperitoneally administered
      lipopolysaccharide induced acute lung injury and increased FE(NO) by 30 +/- 7% (p
      < 0.05). We have demonstrated that it is possible to noninvasively measure E(NO)
      from a single, spontaneously breathing mouse. This novel technique provides a
      stable, reproducible, and responsive measure of E(NO) in mice. This technique
      will be of use in determining cellular and isoform sources of E(NO), as well as
      the role of endogenous NO in lung disease.

PMID- 11316646
TI  - Fog-induced respiratory responses are attenuated by nedocromil sodium in humans.
AB  - Fog inhalation induces cough and bronchoconstriction in patients with asthma, but
      only cough in normal subjects; whether it also influences the pattern of
      breathing is unclear. Nedocromil sodium (NCS) inhibits the cough response to
      inhalation of several pharmacological agents but its effects on fog-induced cough
      and changes in the pattern of breathing are unknown. We evaluated the effects of
      no drug, placebo, and 4- and 8-mg NCS administration on the cough threshold and
      changes in the pattern of breathing during fog inhalation in 14 healthy subjects.
      Measurements of tidal volume (VT), duration of inspiratory and expiratory times
      (TI and TE, respectively), total duration of the respiratory cycle (TT), mean
      inspiratory flow (VT/TI), duty cycle (TI/TT), respiratory frequency (f, 60/TT),
      and inspiratory minute ventilation (V I) were obtained by inductive
      plethysmography. Median cough threshold values were unaffected by placebo, but
      were increased (p < 0.01) by both NCS doses. In no-drug and placebo trials,
      inhalation of the threshold fog concentration caused increases in both VT/TI and
      V I (p always < 0.05) due to selective increases (p < 0.01) in VT. These changes
      were markedly attenuated by both NCS doses administration. Thus, fog induces
      coughing and increases in VT, VT/ TI, and V I in healthy subjects; NCS possesses
      antitussive effects and attenuates fog-induced changes in the pattern of
      breathing, possibly through inhibition of rapidly adapting "irritant" receptors.

PMID- 11316647
TI  - Differential effects of airway anesthesia on ozone-induced pulmonary responses in
      human subjects.
AB  - We examined the effect of tetracaine aerosol inhalation, a local anesthetic, on
      lung volume decrements, rapid shallow breathing, and subjective symptoms of
      breathing discomfort induced by the acute inhalation of 0.30 ppm ozone for 65 min
      in 22 ozone-sensitive healthy human subjects. After 50 min of ozone inhalation
      FEV(1) was reduced 24%, breathing frequency was increased 40%, tidal volume was
      decreased 31%, and total subjective symptom score was increased (71.2, compared
      with 3.8 for filtered air exposure). Inhalation of tetracaine aerosol resulted in
      marked reductions in ozone-induced subjective symptoms of throat tickle and/or
      irritation (92.1%), cough (78.5%), shortness of breath (72.5%), and pain on deep
      inspiration (69.4%). In contrast, inhalation of tetracaine aerosol (mass median
      aerodynamic diameter of 3.52 microm with a geometric standard deviation of 1.92)
      resulted in only minor and inconsistent rectification of FEV(1) decrements (5.0%)
      and breathing frequency (-3.8%) that was not significantly different from that
      produced by saline aerosol alone (FEV(1), 5.1% and breathing frequency, -2.7%).
      Our data are consistent with afferent endings located within the large conducting
      airways of the tracheobronchial tree being primarily responsible for ozone
      induced subjective symptoms and provides strong evidence that ozone-induced
      inhibition of maximal inspiratory effort is not dependent on conscious sensations
      of inspiratory discomfort.

PMID- 11316648
TI  - Breathing He-O2 increases ventilation but does not decrease the work of breathing
      during exercise.
AB  - We previously observed an increase in minute ventilation (V E) with resistive
      unloading (He-O2 breathing) in healthy elderly subjects with normal pulmonary
      function. To investigate the effects of resistive unloading in elderly subjects
      with mild chronic airflow limitation (FEV(1)/FVC: 61 +/- 4%), we studied 10
      elderly men and women 70 +/- 3 yr of age. These subjects performed graded cycle
      ergometry to exhaustion, once breathing room air and once breathing a He-O2 gas
      mixture (79% He, 21% O2). V E, pulmonary mechanics, and PET(CO2) were measured
      during each 1-min increment in work rate. Data were analyzed by paired t test at
      rest, at ventilatory threshold (VTh), and during maximal exercise. V E was
      significantly (p < 0.05) increased at VTh (3.4 +/- 4.0 L/min or 12 +/- 15%
      increase) and maximal exercise (15.2 +/- 9.7 L/min or 22 +/- 13% increase) while
      breathing He-O2. Concomitant to the increase in V E, PET(CO2) was decreased at
      all levels (p < 0.01), whereas total work of breathing against the lung was not
      different. We concluded that V E is increased during He-O2 breathing because of
      resistive unloading of the airways and the maintenance of the relationship
      between the work of breathing and exercise work rate.

PMID- 11316649
TI  - Evaluation of exogenous surfactant in HCL-induced lung injury.
AB  - The efficacy of exogenous surfactant administration is influenced by numerous
      factors, which has resulted in variable outcomes of clinical trials evaluating
      this treatment for the acute respiratory distress syndrome (ARDS). We
      investigated several of these factors in an animal model of acid aspiration
      including different surfactant preparations, and different delivery methods. In
      addition, high-frequency oscillation (HFO), a mode of mechanical ventilation
      known to recruit severely damaged lungs, was utilized. Lung injury was induced in
      adult rabbits via intratracheal instillation of 0.2 N HCl followed by
      conventional mechanical ventilation (CMV) until Pa(O2)/FI(O2) values ranged from
      220 to 270 mm Hg. Subsequently, animals were given one of three surfactants
      administered via three different methods and physiological responses were
      assessed over a 1-h period. Regardless of the surfactant treatment strategy
      utilized, oxygenation responses were not sustained. In contrast, HFO resulted in
      a superior response compared with all surfactant treatment strategies involving
      CMV. The deterioration in physiological parameters after surfactant treatment was
      likely due to overwhelming protein inhibition of the surfactant. In conclusion,
      various surfactant treatment strategies were not effective in this model of lung
      injury, although the lungs of these animals were recruitable with HFO, as
      reflected by the acute and sustained oxygenation improvements.

PMID- 11316650
TI  - Exhaled and nasal nitric oxide as a marker of pneumonia in ventilated patients.
AB  - Because inflammation stimulates the expression of inducible nitric oxide (NO)
      synthase (iNOS) with an associated increased local NO production, we hypothesized
      that patients with pneumonia would have increased excretion of NO into their
      airways. To test this hypothesis, NO was measured in the exhaled air and from the
      nasal cavities of 49 consecutively intubated and mechanically ventilated patients
      in our ICU. After excluding NO gas contamination in the inspiratory circuit,
      nasal NO and end-expiratory and mean exhaled tracheal NO levels and plasma
      nitrate concentrations were measured using a fast response chemiluminescence
      analyzer. Twenty-one patients (43%) presented with infectious pneumonia. End-
      expiratory exhaled NO concentrations were significantly higher in patients with
      pneumonia as compared with patients without pneumonia (5.9 +/- 1 ppb versus 3.2
      +/- 0.5 ppb, p < 0.01). Similarly, mean nasal NO was higher in patients with
      pneumonia (1039 +/- 138 ppb versus 367 +/- 58 ppb, p = 0.003). Plasma nitrate
      levels did not differ between patient groups. Threshold values of tracheal or
      nasal NO were defined and subsequently validated in 60 other patients. Positive
      and negative values of a maximal tracheal level > 5 ppb for pneumonia were 74%
      and 89%, respectively. Thus tracheal and nasal NO levels may be of help in
      distinguishing patients with acute pneumonia from other causes. Furthermore,
      because these differences in airway NO levels were not paralleled in blood
      nitrite concentrations, we conclude that pneumonia per se is not associated with
      systemic NO production.

PMID- 11316651
TI  - Does gastric juice pH influence tonometric PCO2 measured by automated air
      tonometry?
AB  - To determine the influence of changes in gastric juice pH due to intravenous
      administration of pentagastrin and omeprazole on intramucosal regional PCO2
      (Pr(CO2)), we investigated 17 healthy human volunteers. Gastric juice pH was
      obtained from a glass pH electrode for continuous gastric juice pH measurement
      and Pr(CO2))was measured by using automated air tonometry. After baseline (8:00
      A.M.-9:00 A.M.) the subjects received 0.6 microg/kg/h pentagastrin intravenously
      for 1 h (9:00 A.M.-10:00 A.M., after stimulation 10:00 A.M.-11:00 A.M.) and 40 mg
      omeprazole intravenously (after omeprazole 11:00 A.M.-3:00 P.M.). Following
      pentagastrin administration gastric juice pH significantly decreased from 1.2 +/-
      0.4 to 0.6 +/- 0.4 (mean +/- SD, p < 0.007, versus baseline), whereas omeprazole
      transiently increased luminal pH up to 4.4 +/- 1.7 (p < 0.007 versus baseline).
      These subsequent changes in gastric juice pH were accompanied by a significant
      increase in Pr(CO2) from 48 +/- 12 to 61 +/- 17 mm Hg (p < 0.007 versus baseline)
      and a decrease to 44 +/- 5 mm Hg (p < 0.002 versus pentagastrin), respectively. A
      gastric juice pH > 4 considerably reduces mean gastric Pr(CO2) and
      interindividual variability. Thus omeprazole may improve the validity of gastric
      tonometry data.

PMID- 11316652
TI  - Improved activity of an actin-resistant DNase I variant on the cystic fibrosis
      airway secretions.
AB  - In cystic fibrosis (CF), actin and DNA originating from inflammatory cells
      contribute to the thickness of airway secretions. Actin can bind to DNA-rich
      fibers and potently inhibit the enzymatic activity of rhDNase. The in vitro
      effects of the actin-resistant rhDNase variant (A114R) were analyzed and compared
      with those of the wild-type rhDNase. Frozen and thawed CF airway secretions were
      incubated for 30 min with different concentrations (0.1, 0.5, 1, 5, or 10
      microg/ml) of either actin-resistant rhDNase or wild-type rhDNase. We observed
      that both the wild-type and the actin-resistant rhDNase significantly decreased
      (p < 0.05 and p < 0.001, respectively) the airway secretion viscosity. The
      decrease in airway secretion viscosity was significant even at low concentrations
      (0.1 microg/ml) of the actin-resistant variant. Incubation with the actin
      resistant variant resulted in a significant decrease (p < 0.02) of the airway
      secretion contact angle and cough transport. A significantly higher (p < 0.01)
      increase in contact angle and cough transport of airway secretions was observed
      at 10 microg/ml with the actin-resistant variant as compared with the wild-type
      rhDNase. The present study had demonstrated that the actin-resistant rhDNase
      variant (A114R) has an enhanced capacity to improve the physical properties and
      cough transport of airway secretions from patients with cystic fibrosis.

PMID- 11316653
TI  - Effects of gestation and antenatal steroid on airway and tissue mechanics in
      newborn lambs.
AB  - The aim of this study was to partition airway and parenchymal mechanics in
      newborn lambs at different gestations and following variable exposure to
      antenatal maternal betamethasone using the forced oscillation technique (FOT).
      Pulmonary impedance data were collected in 37 sedated and intubated apneic lambs
      with the FOT between 0.5 and 20 Hz and fitted by a model to estimate airway
      resistance (Raw) and inertance (Iaw) and the coefficients of tissue resistance
      (GL) and elastance (HL). Total respiratory resistance (Rrs) was also determined
      during tidal ventilation by using the multiple linear regression technique.
      Advancing gestation or increasing antenatal steroid exposure had no clinically
      significant effect on the values of Raw and Iaw, whereas Rrs and both GL and HL
      decreased markedly. There was a decrease in tissue hysteresivity (GL/HL) with
      repeated antenatal steroid exposure. Partitioning of lung mechanics highlights
      the dominant contribution of the tissues to the total respiratory resistance in
      the immature ovine lung. Clinically relevant changes in lung mechanics associated
      with structural and functional maturation of the immature ovine lung are
      primarily confined to the tissue compartment.

PMID- 11316654
TI  - Effects of S-nitrosation of hemoglobin on hypoxic pulmonary vasoconstriction and
      nitric oxide flux.
AB  - Free hemoglobin (Hb) augments hypoxic pulmonary vasoconstriction (HPV),
      ostensibly by scavenging nitric oxide (NO). However, recent evidence suggests
      that Hb that is S-nitrosated may act as an NO donor and vasodilator. We studied
      the effects of oxyHb, Hb that is chemically modified to prevent heme binding or
      oxidation of NO (cyanometHb), and Hb that is S-nitrosated (SNO-Hb and SNO
      cyanometHb) on HPV, expired NO (eNO), and perfusate S-nitrosothiol (SNO)
      concentration in isolated, perfused rabbit lungs. Perfusate containing either 4
      microM oxyHb or SNO-Hb increased normoxic pulmonary artery pressure (Ppa),
      augmented HPV dramatically, and resulted in an 80% fall in eNO in comparison to
      perfusion with buffer, whereas 4 microM cyanometHb or SNO-cynanometHb had no
      effect on these variables. Excess glutathione (GSH) added to perfusate containing
      SNO-Hb resulted in a 20 to 40% fall in the perfusate SNO concentration, with a
      concomitant increase in metHb content, without affecting Ppa, HPV, or eNO. In
      conclusion, free Hb augments HPV by scavenging NO, an effect that is not
      prevented by S-nitrosation. NO released from SNO-Hb in the presence of GSH does
      not produce measurable vascular effects in the lung or changes in eNO because of
      immediate oxidation and metHb formation.

PMID- 11316655
TI  - Effects of lung volume reduction surgery for emphysema on diaphragm dimensions
      and configuration.
AB  - Part of the functional benefit provided by lung volume reduction surgery (LVRS)
      may be related to improvement in respiratory muscle function resulting from
      changes in diaphragm dimension and configuration. To study these changes, we
      obtained 3D reconstructions of the muscle using spiral computed tomography in 11
      patients with severe emphysema before and 3 mo after surgery, and in 11 normal
      subjects matched for sex, age, height, and weight. Bilateral LVRS was performed
      by thoracoscopy in eight patients and by sternotomy in three patients.
      Acquisitions were made in the supine posture at relaxed FRC, midinspiratory
      capacity, and TLC. On average, LVRS produced a 51 +/- 11% increase in FEV(1) and
      a 30 +/- 4% decrease in FRC. The total surface area of the diaphragm (A(di)) and
      of the zone of apposition (A(ap)) at FRC increased by 17 +/- 4% and 43 +/- 8%,
      respectively, but the surface area of the dome did not change. Compared with the
      values recorded in the normal subjects, postoperative values of A(di) and A(ap)
      at FRC were reduced by 11% (p < 0.05) and 24% (p < 0.005), respectively. The
      curvature of the dome increased at TLC in the left sagittal plane, but was
      otherwise unaffected by the procedure. We conclude that LVRS substantially
      increases A(di) and A(ap), but does not significantly improve diaphragm
      configuration at FRC.

PMID- 11316656
TI  - Production of inflammatory cytokines in ventilator-induced lung injury: a
      reappraisal.
AB  - We investigated the production of proinflammatory cytokines by the lung during
      high mechanical stretch in vivo. To do this, we subjected rats to high-volume (42
      ml/kg tidal volume [VT]) ventilation for 2 h. The animals developed severe
      pulmonary edema and alveolar flooding, with a high protein concentration in
      bronchoalveolar lavage fluid (BALF). The animals' BALF contained no tumor
      necrosis factor (TNF)-alpha, negligible amounts of interleukin (IL)-1beta, and
      less than 300 pg/ml of the chemokine macrophage inflammatory protein (MIP)-2, an
      amount similar to that found in rats ventilated with 7 ml/kg VT. Systemic
      cytokine levels were below the detection threshold. Because isolated lungs have
      been shown to produce high levels of proinflammatory cytokines when ventilated
      with a similarly high VT for the same duration (Tremblay, et al. J Clin Invest
      1997;99:944-952), we reconsidered this specific issue. We ventilated isolated,
      unperfused rat lungs for 2 h with 7 ml/kg or 42 ml/kg VT, or maintained them in a
      statically inflated state. Negligible amounts of TNF-alpha were found in the BALF
      whatever the ventilatory condition applied. The BALF IL-1beta concentration was
      slightly elevated and higher in lungs ventilated with 42 ml/kg VT than in those
      ventilated with 7 ml/kg VT or in statically inflated lungs (p < 0.05). The BALF
      MIP-2 concentration was moderately elevated in all isolated lungs (200 to 300
      pg/ml), and was slightly higher (p < 0.05) in lungs ventilated with 42 ml/kg VT.
      After lipopolysaccharide (LPS) challenge, high levels of TNF-alpha, IL-1beta, and
      MIP-2 were found in the animals' plasma before the lungs were removed. Negligible
      amounts of TNF-alpha and IL-1beta were retrieved from the BALF of statically
      inflated lungs. The concentrations of TNF-alpha and IL-1beta were higher in the
      BALF of ventilated lungs (p < 0.001). The TNF-alpha level did not differ with the
      magnitude of VT, whereas the level of IL-1beta was significantly higher in BALF
      of lungs ventilated with 42 ml/kg VT (p < 0.01). The MIP-2 concentrations were
      similar for the two ventilatory conditions. These results suggest that
      ventilation that severely injures lungs does not lead to the release of
      significant amounts of TNF-alpha or IL-1beta by the lung in the absence of LPS
      challenge but may increase lung MIP-2 production.

PMID- 11316657
TI  - Chemical control stability in patients with obstructive sleep apnea.
AB  - The role of chemical control instability in the pathogenesis of obstructive sleep
      apnea (OSA) is not clear. We studied 32 patients with OSA during sleep while
      their upper airway was stabilized with continuous positive airway pressure.
      Twelve patients had repetitive OSA whenever they were asleep, regardless of body
      position or sleep stage, and were classified as having severe OSA (apnea-hypopnea
      index [AHI] = 88 +/- 19). The remaining 20 patients had sporadic OSA or
      repetitive OSA for only part of the time (mild/moderate OSA; AHI = 27 +/- 16).
      Susceptibility to periodic breathing (PB) was assessed by gradually increasing
      controller gain, using proportional assist ventilation. The increase in loop gain
      (LG) at each assist level was quantified from the ratio of assisted tidal volume
      (VT) to the VT obtained during single-breath reloading tests (VT amplification
      factor [VTAF]). Nine of 12 patients with severe OSA developed PB, with recurrent
      central apneas, whereas only six of 20 patients in the mild/moderate group
      developed PB (p < 0.02). This difference was observed despite the subjection of
      the mild/moderate group to greater amplification of LG; the highest values of
      VTAF in the mild/moderate and severe groups were 2.7 +/- 1.0 and 1.9 +/- 0.7,
      respectively (p < 0.01). We conclude that the chemical control system is more
      unstable in patients with severe OSA than in patients with milder OSA. We
      speculate that this may contribute to the severity of OSA, at least in some
      patients.

PMID- 11316658
TI  - Serotonergic modulation of ventilation and upper airway stability in obese Zucker
      rats.
AB  - To elucidate the role of serotonin in the maintenance of normal breathing and
      upper airway (UA) patency in obesity, we studied the effects of systemic
      administration of ritanserin, a serotonin (5-HT) 2A and 2C receptor antagonist,
      on ventilation (V E) during room air breathing and during hypoxic (10% O2) and
      hypercapnic (4% CO2) ventilatory challenges in awake young (6-8 wk) and older (7
      8 mo) obese and lean Zucker (Z) rats. Older obese Z rats adopted a more rapid
      shallow breathing pattern compared with older lean rats. The administration of
      ritanserin (1 mg/kg intraperitoneally) to older obese rats resulted in a
      reduction in V E (439 +/- 35 [SD] to 386 +/- 41 ml/kg/min, p < 0.01), a decrease
      in respiratory rate, a prolongation of inspiratory time, and an increase in V O2
      (16.4 +/- 1.7 to 18.2 +/- 1.9 ml/kg(0.75)/min, p < 0.05) during room air
      breathing. By comparison, it had little effect on ventilation in young lean and
      obese Z or older lean Z rats. Ritanserin also had no effect on ventilatory
      responses to either hypoxia or hypercapnia in young or older lean and obese Z
      rats. The collapsibility of the isolated UA was examined in older Z rats. The
      pharyngeal critical pressure (Pcrit) of older obese rats was significantly
      greater than that of lean rats (p < 0.05), indicating that obese rats have more
      collapsible UA than lean rats. The administration of ritanserin significantly
      increased Pcrit in older obese rats (-1.6 +/- 0.3 to -0.8 +/- 0.2 cm H2O, p <
      0.01) and in lean rats (-3.1 +/- 1.0 to -2.4 +/- 0.6 cm H2O, p < 0.05). We
      suggest that the 5-HT(2A/2C) receptor subtype plays an important role in the
      maintenance of UA stability and normal breathing in obesity, and we speculate
      that older obese Z rats may have augmented serotonergic control of UA dilator
      muscles as a mechanism to prevent pharyngeal collapse.

PMID- 11316659
TI  - Attenuation of interleukin 8-induced nasal inflammation by an inhibitor peptide.
AB  - Polymorphonuclear neutrophils (PMNs) infiltrate tissue in response to
      chemoattractants, including interleukin 8 (IL-8). Infiltrating PMNs clear
      microorganisms but also cause tissue damage. We previously reported the presence
      in human bronchial lavage of a peptide that inhibits PMN functions. The current
      project assessed (1) effects of a synthetic analog of this peptide (synthetic
      neutrophil inhibitor peptide, SNIP) on IL-8-induced nasal inflammation in humans,
      (2) effects of SNIP on PMN apoptosis and chemotaxis, (3) specific binding of SNIP
      to PMNs, and (4) evidence of larger molecules with the SNIP sequence. Results
      show that SNIP attenuates IL-8-induced nasal inflammation, inhibits in vitro PMN
      chemotaxis to IL-8, and accentuates PMNs apoptosis. PMNs contain specific SNIP
      binding sites and the integrin CR3 (CD11b/CD18), or a CR3-associated molecule, is
      one SNIP-binding molecule. Chemotaxis to IL-8 is most potently inhibited by SNIP
      in the presence of fibrinogen, a CR3 ligand. Antiserum against the SNIP sequence
      recognizes a 70-kDa protein in bronchoalveolar lavage and an anti-SNIP
      immunoaffinity column binds a 70-kDa protein in U937 cell culture supernatant.
      U937 cell mRNA contains a 1.8-kb transcript detected with degenerate
      oligonucleotides designed from the SNIP sequence. These studies demonstrate that
      a synthetic inhibitor peptide can attenuate in vivo nasal inflammation through
      downregulatory effects on PMNs.

PMID- 11316660
TI  - NK1 receptor stimulation causes contraction and inositol phosphate increase in
      medium-size human isolated bronchi.
AB  - Although contraction of human isolated bronchi is mediated mainly by tachykinin
      NK2 receptors, NK1 receptors, via prostanoid release, contract small-size
      (approximately 1 mm in diameter) bronchi. Here, we have investigated the presence
      and biological responses of NK1 receptors in medium-size (2-5 mm in diameter)
      human isolated bronchi. Specific staining was seen in bronchial sections with an
      antibody directed against the human NK1 receptor. The selective NK1 receptor
      agonist, [Sar(9), Met(O2)(11)]SP, contracted about 60% of human isolated
      bronchial rings. This effect was reduced by two different NK1 receptor
      antagonists, CP-99,994 and SR 140333. Contraction induced by [Sar(9),
      Met(O2)(11)]SP was independent of acetylcholine and histamine release and
      epithelium removal, and was not affected by nitric oxide synthase and
      cyclooxygenase (COX) inhibition. [Sar(9), Met(O2)(11)]SP increased inositol
      phosphate (IP) levels, and SR 140333 blocked this increase, in segments of medium
      and small-size (approximately 1 mm in diameter) human bronchi. COX inhibition
      blocked the IP increase induced by [Sar(9), Met(O2)(11)]SP in small-size, but not
      in medium-size, bronchi. NK1 receptors mediated bronchoconstriction in a large
      proportion of medium-size human bronchi. Unlike small-size bronchi this effect is
      independent of prostanoid release, and the results are suggestive of a direct
      activation of smooth muscle receptors and IP release.

PMID- 11316661
TI  - Subclinical right ventricular dysfunction in cystic fibrosis. A study using
      tissue Doppler echocardiography.
AB  - Patients with severe cystic fibrosis can develop cor pulmonale, but little is
      known about the function of the right ventricle (RV) early in the disease. We
      hypothesized that such patients might have subclinical RV dysfunction, detectable
      by tissue Doppler echocardiography, and related to the severity of lung disease.
      We studied 21 clinically stable patients (Group 1), five patients with severe
      lung disease (Group 2), and 23 age-matched healthy subjects. Patients had
      impaired RV systolic function. The mean (SD) systolic velocities of the RV free
      wall were 8.9 (1.7) cm/s in Group 1, 7.7 (1.0) in Group 2, and 10.8 (1.9) in
      healthy subjects (p < 0.001). The velocities of the tricuspid annulus were less
      in patients (p < 0.0001). Patients had a greater isovolumic relaxation time (p <
      0.001), indicating RV diastolic dysfunction. RV wall thickness was greater in
      patients (0.4 [0.1] versus 0.3 [0.1] cm/m(2), p < 0.01). RV systolic function was
      related to C-reactive protein (r = - 0.66, p < 0.001) and FEV(1) (r = 0.62, p =
      0.003) and diastolic function to interleukin-6 (r = 0.64, p < 0.005). Patients
      with cystic fibrosis have subclinical RV dysfunction, which correlates with the
      severity of lung disease. Tissue Doppler echocardiography provides a quantifiable
      indicator useful for detection and monitoring of disease progression.

PMID- 11316662
TI  - Decreased steroid responsiveness at night in nocturnal asthma. Is the macrophage
      responsible?
AB  - As peripheral blood mononuclear cells from patients with nocturnal asthma (NA)
      exhibit reduced steroid responsiveness at 4:00 A.M. as compared with 4:00 P.M.,
      we hypothesized that NA is associated with increased nocturnal airway cell
      expression of GRbeta, an endogenous inhibitor of steroid action. Ten subjects
      with NA and seven subjects with nonnocturnal asthma (NNA) underwent bronchoscopy
      with bronchoalveolar lavage (BAL) at 4:00 P.M. and 4:00 A.M. BAL lymphocytes and
      macrophages were incubated with dexamethasone (DEX) at 10(-5) to 10(-8) M. DEX
      suppressed proliferation of BAL lymphocytes similarly at 4:00 P.M. and 4:00 A.M.
      in both groups. However, BAL macrophages from NA exhibited less suppression of IL
      8 and TNF-alpha production by DEX at 4:00 A.M. as compared with 4:00 P.M. (p =
      0.0001), whereas in the NNA group DEX suppressed IL-8 and TNF-alpha production
      equally at both time points. GRbeta expression was increased at night only in NA,
      primarily due to significantly increased expression by BAL macrophages (p =
      0.008). IL-13 mRNA expression was increased at night, but only in the NA group
      and addition of neutralizing antibodies to IL-13 reduced GRbeta expression by BAL
      macrophages. We conclude that the airway macrophage may be the airway
      inflammatory cell driving the reduction in steroid responsiveness at night in NA,
      and this function is modulated by IL-13.

PMID- 11316663
TI  - Bronchial interleukin-5 and eotaxin expression in nasal polyposis. Relationship
      with (a)symptomatic bronchial hyperresponsiveness.
AB  - An eosinophilic bronchial inflammation was previously demonstrated in patients
      with nasal polyposis (NP) and asymptomatic bronchial hyperresponsiveness (BHR)
      similar to that observed in asthmatic patients with NP, whereas patients with NP
      without BHR did not. The aim of the study was to investigate the contribution of
      interleukin 5 (IL-5) and eotaxin to the pathogenesis of BHR associated with NP.
      Eleven patients with NP without BHR (Group A), 8 patients with NP and
      asymptomatic BHR (Group B), and 9 patients with NP and asthma (Group C) were
      included. Bronchial biopsies were studied for IL-5 and eotaxin immunoreactivity
      and IL-5 mRNA expression. IL-5 levels were determined in bronchial lavage (BL).
      Compared with Groups A and B, Group C patients exhibited higher numbers of IL-5
      protein(+) cells, IL-5 mRNA(+) cells, and eotaxin(+) cells in bronchial
      submucosa. Compared with Group A, Group B patients showed an increased number of
      IL-5 protein(+) cells, whereas the number of IL-5 mRNA(+) cells and eotaxin(+)
      cells was similar. IL-5 levels in BL were increased only in Group C. Our study
      provides evidence of IL-5 involvement in bronchial eosinophilia and in the
      pathogenesis of asymptomatic BHR associated with NP, whereas both IL-5 and
      eotaxin are involved in asthma associated with NP.

PMID- 11316665
TI  - Dissociation of pulmonary vascular remodeling and right ventricular pressure in
      tissue angiotensin-converting enzyme-deficient mice under conditions of chronic
      alveolar hypoxia.
AB  - The present study was designed to characterize the role of tissue angiotensin
      converting enzyme (ACE) on pulmonary vascular remodeling and its functional
      consequences in chronic hypoxia. On the basis of data obtained by pharmacological
      inhibition of ACE in rats we hypothesized that, under chronic hypoxic conditions,
      tissue ACE-deficient mice show less remodeling of pulmonary arterioles as
      compared with wild-type mice, but have equally increased right ventricular
      pressures. Wild-type and tissue ACE-deficient mice were exposed to chronic
      hypoxia for 4 wk. Absence of tissue ACE did not affect the increase in the mean
      right ventricular pressures (MRVP) and the extent of right ventricular
      hypertrophy under chronic hypoxic conditions. Chronic hypoxia induced significant
      remodeling of pulmonary arterioles in tissue ACE-deficient mice. The percentage
      of completely muscularized arterioles was, however, lower in tissue ACE-deficient
      mice compared with wild-type animals (29 +/- 12 versus 41 +/- 18%, p < 0.05),
      whereas the percentage of partially muscularized arterioles had increased (48 +/-
      11 versus 39 +/- 11%, p < 0.05). No sex-based effects were found. We conclude
      that the absence of tissue ACE does not prevent the MRVP and right ventricular
      weight from increasing during chronic hypoxia in the mouse. Also, pulmonary
      vascular remodeling occurs in hypoxic tissue ACE-deficient mice, albeit to a
      lower level than in mice that do have an intact ACE gene.

PMID- 11316664
TI  - Nitric oxide and protein nitration are eosinophil dependent in allergen
      challenged mice.
AB  - To explore the possible role of eosinophils in NO-mediated tissue injury, we
      studied a murine model of allergic asthma. Male A/J mice were sensitized and
      challenged intranasally with ovalbumin (OVA). Following challenge, the number of
      eosinophils in bronchoalveolar lavage fluid (BALF) increased from 0.4% of total
      cells at baseline (0.02 x 10(4) cells/ml) to 60.2% at 48 h after the challenge
      (9.34 x 10(4) cells/ml). The rise in eosinophil count was accompanied by a 40.3%
      increase in total NO(2-) plus NO(3-) (NO(x)) in BALF. This in turn was
      accompanied by expression of inducible NO synthase (NOS II) in airway epithelial
      and inflammatory cells, as well as by evidence of staining for 3-nitrotyrosine
      (3NT) in peribronchial inflammatory cells and at the epithelial surface. Both
      NO(x) production and 3NT were significantly reduced by pretreatment of the
      challenged mice with the highly specific NOS II inhibitor N-3-aminomethyl-benzyl
      acetamidine-dihydrochloride (1400W), as well as by the nonselective NOS inhibitor
      N(omega)-nitro-L-arginine methyl ester (L-NAME). L-NAME and 1400W also reduced
      the number of BALF eosinophils (37.2% and 61.5%, respectively, as compared with
      the control value), suggesting that NO production by NOS II contributes to
      eosinophil recruitment. To further examine the role of eosinophils, we pretreated
      additional mice with an anti-interleukin (IL)-5 antibody, which reduced BALF
      eosinophilia following OVA challenge by 90.1%. In concert with the decrease in
      eosinophils, the anti-IL-5 antibody reduced NO(x) in BALF almost to the baseline
      value, and decreased the number of 3NT-positive cells in the peribronchial region
      by 74.4%. Western blot analysis of protein extracted from whole lung confirmed
      the reduction in tyrosine nitration by anti-IL-5 antibody. These findings
      indicate that NO and eosinophilic inflammation are closely coupled, and suggest
      that eosinophils are an important source of tyrosine nitration.

PMID- 11316666
TI  - The relation of serum levels of antioxidant vitamins C and E, retinol and
      carotenoids with pulmonary function in the general population.
AB  - Reduced pulmonary function is an important predictor of mortality in the general
      population, and antioxidant vitamins are thought to positively influence
      pulmonary function. Vitamin C, vitamin E, retinol, and carotenoids are powerful
      antioxidants but information about the joint relation of serum levels of these
      antioxidants to pulmonary function is limited. We analyzed the association of
      FEV(1) and FVC with serum vitamins C and E, retinol, and carotenoids (beta
      cryptoxanthin, lutein/zeaxanthin, beta-carotene, and lycopene) in a cross
      sectional study. The analysis was carried out in a sample of 1,616 randomly
      selected residents of Western New York, USA, age 35 to 79 yr and free of
      respiratory disease. Lung function was adjusted for height, age, sex, and race
      and expressed as percentage of predicted normal FEV(1) (FEV(1)%) and FVC (FVC%).
      Participants in the lowest quartile of each of the serum antioxidants had
      consistently lower FEV(1)% and FVC% than those in higher quartiles. Multiple
      linear regression analysis revealed significant associations of vitamin C,
      vitamin E, beta-cryptoxanthin, lutein/zeaxanthin, beta-carotene, and retinol with
      FEV(1)% when these variables were investigated individually after adjustment for
      other covariates (smoking status, pack-years of smoking, weight, eosinophil
      count, and education). When all of these antioxidant vitamins were analyzed
      simultaneously in a multivariate regression model, the strongest association was
      seen with vitamin E and beta-cryptoxanthin. Only retinol showed an independent
      effect on FEV(1)% after controlling for vitamin E and beta-cryptoxanthin. As for
      FEV(1)%, vitamin E and beta-cryptoxanthin were most strongly related to FVC% when
      all variables were considered in the multivariate regression model. The
      differences in FEV(1) associated with a reduction of one standard deviation of
      serum vitamin E or beta-cryptoxanthin were equivalent to the negative influence
      of approximately 1 to 2 yr of aging. Our findings support the hypothesis that
      antioxidant vitamins may play a role in respiratory health and that vitamin E and
      beta-cryptoxanthin appear to be stronger correlates of lung function than other
      antioxidant vitamins.

PMID- 11316667
TI  - Global strategy for the diagnosis, management, and prevention of chronic
      obstructive pulmonary disease. NHLBI/WHO Global Initiative for Chronic
      Obstructive Lung Disease (GOLD) Workshop summary.

PMID- 11316668
TI  - Retractions in AJRCCM.

PMID- 11316669
TI  - Comparable efficacy of administration with face mask or mouthpiece of nebulized
      budesonide suspension for infants and young children with persistant asthma.

PMID- 11316670
TI  - Inhaled corticosteroids for persistent wheeze in preschool children.

PMID- 11316671
TI  - Contribution of expiratory muscle pressure to dynamic intrinsic positive end
      expiratory pressure.

PMID- 11316672
TI  - Lung deposition of inhaled drugs increases with age?

PMID- 11316673
TI  - Sputum induction versus fiberoptic bronchoscopy in the diagnosis of tuberculosis.

PMID- 11316674
TI  - Screening for familial adenomatous polyposis.

PMID- 11316675
TI  - Breast feeding and the risks of viral transmission.

PMID- 11316676
TI  - Meningococcal group C conjugate vaccines.

PMID- 11316677
TI  - Infant growth monitoring.

PMID- 11316678
TI  - Uk audit of childhood growth hormone prescription, 1998.
AB  - AIMS: To identify all young people prescribed growth hormone in the UK as of 1
      October 1998 and to determine their age, sex, and the indication for therapy.
      METHODS: Cross sectional national postal audit through members of the British
      Society for Paediatric Endocrinology and Diabetes (BSPED) and other
      paediatricians identified as potential prescribers of growth hormone. Main
      outcome measures were age, sex, and numbers of children receiving growth hormone
      by diagnostic category, analysed throughout the UK and by NHS region. RESULTS: A
      total of 3228 children (aged 0.3 to 23.9 years) receiving growth hormone were
      identified by contacting 171 paediatricians (149 BSPED members). Of these, 2395
      (74%) were identified who were under 16 years-representing 19.8/100 000 children
      in that age range in the UK-and in whom full data concerning diagnostic category
      were available. In the under 16s, there were 1209 (50.4%) boys and 1186 (49.6%)
      girls (excluding the 477 girls with Turner's syndrome: 63% boys and 37% girls). A
      total of 78% of the prescriptions were for licensed indications (primary and
      secondary growth hormone deficiency, Turner's syndrome, and chronic renal
      disease); 22% were for unlicensed indications (intrauterine growth restriction,
      bony dysplasia, Noonan syndrome, and other "short normals"). These proportions
      are similar to those reported in previous audits and by postmarketing
      surveillance from Pharmacia & Upjohn Ltd in the year 2000. Patterns of treatment
      were relatively uniform between regions. CONCLUSIONS: A national audit of UK
      growth hormone prescription indicates uniform prescribing practice between
      regions, low levels of prescription beyond licensed indications, and stable
      patterns of prescribing practice over the past two years.

PMID- 11316679
TI  - Determining the common medical presenting problems to an accident and emergency
      department.
AB  - All accident and emergency (A&E) attendances over a one year period were
      prospectively studied in order to determine common medical presenting problems.
      Data were collected on children (0-15 years) attending a paediatric A&E
      department in Nottingham between February 1997 and February 1998. A total of 38
      982 children were seen. The diagnoses of 26 756 (69%) were classified as trauma
      or surgical, and 10 369 (27%) as medical; 1857 (4%) could not be classified. The
      commonest presenting problems reported for "medical" children were breathing
      difficulty (31%), febrile illness (20%), diarrhoea with or without vomiting
      (16%), abdominal pain (6%), seizure (5%), and rash (5%). The most senior doctor
      seeing these patients in A&E was a senior house officer (intern or junior
      resident) in 78% of cases, paediatric registrar (senior resident) in 19%,
      consultant (attending physician) in 1.4%, and "other" in 2.6%. Guidelines
      developed for A&E should target the commonest presenting problem categories, six
      of which account for 83% of all medical attendances, and be directed towards
      senior house officers.

PMID- 11316680
TI  - A prospective evaluation of community acquired gastroenteritis in paediatric
      practices: impact and disease burden of rotavirus infection.
AB  - AIMS: To examine the disease burden and epidemiology of community acquired
      rotavirus gastroenteritis in Austrian children treated in a paediatric practice.
      METHODS: A prospective, population based, multicentre study in four paediatric
      practices and two children's hospitals (Innsbruck and Leoben). Children </= 48
      months of age presenting with gastroenteritis during a six month period of
      rotavirus peak between December 1997 and May 1998 were included. Prospective
      testing of stool samples for rotavirus was performed using ELISA. RESULTS: A
      total of 6969 children were enrolled; 171 (2.4%) had community acquired
      gastroenteritis. Of 144 children who could be included in further analysis, 49
      (34%; median age 16.7 months) were rotavirus positive, and 95 (66%; median age
      17.0 months) were rotavirus negative. Three of the rotavirus positive children
      (median age 14.6 months) were hospitalised. The severity of rotavirus positive
      gastroenteritis was significantly higher than that of rotavirus negative
      gastroenteritis. The incidence of community acquired gastroenteritis was 4.67 per
      100 children per year, and of rotavirus positive gastroenteritis 1.33 per 100
      children per year. CONCLUSION: Rotavirus is a relevant cause of community
      acquired gastroenteritis in children aged 4 years and younger treated by a
      paediatrician. The data can be used as a basis for developing strategies to
      prevent infection.

PMID- 11316682
TI  - Systematic review of the occurrence of infantile colic in the community.
AB  - AIMS: To assess the occurrence of infantile colic in the community and the need
      for professional help; and to study the influences of potential determinants of
      infantile colic. METHODS: Surveys were identified by a systematic search in
      Medline (1966-98) and Embase (1988-98). Retrieved publications were checked for
      references. Studies selected were community based, prospective, and retrospective
      surveys on the occurrence of infantile colic published in English, German,
      French, or Dutch. Occurrence rates were calculated as percentages. Methodological
      quality of the surveys was assessed by two assessors independently with a
      standardised criteria list containing items on method of data gathering,
      definition of colic, and drop out rate. RESULTS: Fifteen community based surveys
      were identified. The methodological quality varied considerably and was generally
      low. Even the two most methodologically sound prospective studies yielded widely
      varying cumulative incidence rates of 5-19%. Referral rates or the need to seek
      help because of crying were consistently lower than occurrence rates for
      prolonged crying as such. Gender, socioeconomic class, type of feeding, family
      history of atopy, and parental smoking were not shown to be associated with
      colic. CONCLUSION: Occurrence rates of infantile colic vary greatly according to
      methodological quality. A considerable number of parents reporting prolonged
      crying do not seek or need professional help.

PMID- 11316683
TI  - An auditable protocol for treating attention deficit/hyperactivity disorder.
AB  - We present an auditable protocol for attention deficit/hyperactivity disorder
      (ADHD) or hyperkinetic disorder. The protocol is derived from standard
      recommendations and evidence, and is intended for outpatient medical clinic
      practice in secondary care. Suggested side effect rating scales are included.

PMID- 11316684
TI  - Adrenaline syringes are vastly over prescribed.

PMID- 11316685
TI  - Changes in paediatric resuscitation knowledge among doctors.
AB  - AIMS: To investigate whether paediatricians have improved their resuscitation
      knowledge since 1992, and whether those who have attended a paediatric
      resuscitation course have greater knowledge than those who have not. METHODS:
      Telephone survey of 94 resident paediatricians admitting emergency cases.
      Questions on clinical scenarios were asked and adherence to internationally
      agreed guidelines in answering was determined. RESULTS: There were significantly
      more correct answers to 9/10 questions in 1999 compared to 1992. The 1999 doctors
      who had attended a course scored significantly better in 3/10 questions and
      achieved a higher total score (5.43 versus 4.55). CONCLUSIONS: Knowledge has
      improved since 1992; this has been over the period in which paediatric
      resuscitation courses were introduced. In 1999 those who had been on a course
      were more knowledgeable than those who had not.

PMID- 11316687
TI  - The prognosis of childhood abdominal migraine.
AB  - AIMS: To determine the clinical course of childhood abdominal migraine, seven to
      10 years after the diagnosis. METHODS: A total of 54 children with abdominal
      migraine were studied; 35 were identified from a population survey carried out on
      Aberdeen schoolchildren between 1991 and 1993, and 19 from outpatient records of
      children in the same age group who had attended the Royal Aberdeen Children's
      Hospital. Controls were 54 children who did not have abdominal pain in childhood,
      matched for age and sex, obtained from either the population survey or the
      patient administration system. Main outcome measures were presence or resolution
      of abdominal migraine and past or present history of headache fulfilling the
      International Headache Society (IHS) criteria for the diagnosis of migraine.
      RESULTS: Abdominal migraine had resolved in 31 cases (61%). Seventy per cent of
      cases with abdominal migraine were either current (52%) or previous (18%)
      sufferers from headaches that fulfilled the IHS criteria for migraine, compared
      to 20% of the controls. CONCLUSIONS: These results support the concept of
      abdominal migraine as a migraine prodrome, and suggest that our diagnostic
      criteria for the condition are robust.

PMID- 11316688
TI  - Antibiotic resistance and antibiotic sensitivity based treatment in Helicobacter
      pylori infection: advantages and outcome.
AB  - AIMS: To compare two strategies for the eradication of Helicobacter pylori
      infection. METHODS: Groups 1 and 2 each consisted of 75 consecutive patients.
      Patients in group 1 were treated with two antibiotics based on antibiotic
      susceptibility testing; those in group 2 received amoxycillin and clarithromycin
      for eight days, together with either ranitidine or omeprazole. Eradication rate
      was assessed in both groups six months after treatment. RESULTS: In group 1, H
      pylori grew in culture in 63/75 cases. Susceptibility testing showed that 35/63
      isolates were resistant to metronidazole, 10/63 to clarithromycin, 2/63 to
      ampicillin, 1/63 to tetracycline, and 5/63 to both clarithromycin and
      metronidazole. In group 1 the infection was eradicated in 96% of the initial 75
      subjects, and in 98% of the subjects treated according to the antibiotic assay
      (62/63). As two patients were lost at follow up the overall eradication rate was
      99%. In group 2, eradication was achieved in 61/75 subjects (81%). This was
      significantly lower than the percentage of eradication observed in group 1 (81%
      versus 99%). CONCLUSIONS: Antibiotic susceptibility tests are useful in childhood
      as a very high percentage of subjects are cured. This approach is costly, but
      selective antibiotic treatment contributes to limit further development of
      antibiotic resistance, and money is saved in terms of reinvestigation and further
      repeated treatments.

PMID- 11316691
TI  - Isolated splenomegaly as the presenting feature of Niemann-Pick disease type C.
AB  - WE DESCRIBE FOUR PATIENTS WITH NIEMANN: Pick disease type C (NPC), in whom the
      presentation was isolated splenic enlargement; this remained the only abnormality
      for a number of years. Diagnosis can be suggested by either finding abnormal
      storage material in a tissue biopsy specimen or by showing a modest elevation in
      plasma chitotriosidase activity. In patients with suggestive abnormalities,
      filipin staining of a skin fibroblast sample should confirm the abnormality in
      cholesterol trafficking. Formal esterification studies and mutation analysis
      should also be performed, especially if prenatal testing is to be performed in
      subsequent pregnancies. If the diagnosis is not considered and established, the
      family are at risk of having further affected children. Investigation of patients
      with isolated splenomegaly is not complete until NPC has been excluded.

PMID- 11316690
TI  - Safety and ethics of bronchoscopy and endobronchial biopsy in difficult asthma.
AB  - AIM: To investigate the safety of bronchoscopy and endobronchial biopsy in
      children with difficult asthma, and discuss the ethical issues associated with
      the procedure. METHODS: A three year prospective observational study was
      performed in two tertiary paediatric respiratory centres specialising in the
      management of children with difficult asthma. A total of 48 children with
      difficult asthma and 35 non-asthmatic children were studied. RESULTS: Flexible
      bronchoscopy was performed under general anaesthesia in 38 children with
      difficult asthma, and rigid bronchoscopy was performed in 10, following a two
      week course of prednisolone. Endobronchial biopsy was performed in 47 patients.
      Perioperative complications occurred in one asthmatic undergoing flexible
      bronchoscopy (desaturation) and in two undergoing rigid bronchoscopy
      (desaturation in one, and bronchospasm and desaturation in one). There were no
      cases of significant bleeding or pneumothorax among the asthmatics. Flexible
      bronchoscopy was performed in 35 non-asthmatic patients with a variety of
      clinical indications. The total number of perioperative complications was greater
      in the non-asthmatics undergoing flexible bronchoscopy than in the asthmatics (17
      complications in 35 children versus one in 38). Fever requiring hospital
      admission was documented in two asthmatics following bronchoscopy. Four
      asthmatics reported an increase in symptoms in the week following bronchoscopy.
      CONCLUSIONS: Bronchoscopy and endobronchial biopsy under general anaesthesia can
      be performed safely in children with difficult asthma, when the bronchoscopist
      and anaesthetist are suitably trained. The procedure is acceptable to the
      families involved.

PMID- 11316692
TI  - Niflumic acid and cutaneous reactions in children.
AB  - In a case control study of adverse drug reactions in children, the odds ratio of
      developing a serious mucocutaneous event among users of niflumic acid, adjusted
      for concomitant use of all other drugs, was 4.9 (95% CI 1.9 to 12.8). Given the
      availability of safer analgesics and antipyretics, there is no indication, in our
      opinion, that requires the prescription of substances which bear an increased
      risk.

PMID- 11316693
TI  - Bronchoconstriction following nebulised colistin in cystic fibrosis.
AB  - Nebulised colistin is regularly used as antipseudomonal therapy in children with
      cystic fibrosis. We assessed bronchoconstriction in response to nebulised
      colistin in 58 children. Nebulised colistin significantly reduced FEV(1),
      MEF(25%), and SaO(2) for 15 minutes. In 20 children the reduction was greater
      than 10% from baseline FEV(1), and was still at that level in five at 30 minutes.
      Subjective assessment, baseline FEV(1), and serum IgE were unable to identify
      susceptible children. It is recommended that children receiving colistin should
      be carefully assessed for bronchoconstriction.

PMID- 11316694
TI  - Acute neurology and neurophysiology of haemolytic-uraemic syndrome.
AB  - Involvement of the central nervous system (CNS) is found in around 30% of
      children with haemolytic-uraemic syndrome (HUS). This complication is the single
      most common cause of mortality and also a major contributor to the morbidity
      associated with HUS. We reviewed 22 children with HUS and acute CNS involvement.
      Both global and focal derangements occurred, and in survivors, early regional EEG
      abnormalities-especially those in the occipital and temporal areas-were
      prognostically useful.

PMID- 11316695
TI  - Growth hormone and segmental growth in survivors of head and neck embryonal
      rhabdomyosarcoma.
AB  - AIMS: To assess the impact of treatment for embryonal rhabdomyosarcoma on spinal
      growth and limb length and examine the response of these parameters to growth
      hormone (GH) treatment. METHODS: We conducted a retrospective case note review of
      17 survivors of head and neck rhabdomyosarcoma followed up at a single
      institution. All children had been treated with chemotherapy and local
      radiotherapy. Growth velocity, height, sitting height, and subischial limb length
      SDS scores were analysed. RESULTS: Growth failure secondary to isolated GH
      deficiency (GHD) developed in 7/17 patients. GHD occurred at a median (range) of
      3.4 (1.3-9.9) years after radiotherapy tumour doses of 46 (40-50) Gy. Growth
      velocity, height, and subischial limb length SDS were significantly reduced in
      the GHD group and improved with GH therapy. CONCLUSIONS: GH treatment resulted in
      a significant improvement in sitting height SDS. We discuss the unexpected
      improvement in spinal growth in survivors with GHD.

PMID- 11316696
TI  - Short stature in Noonan syndrome: response to growth hormone therapy.
AB  - BACKGROUND: Growth hormone (GH) has been used to promote growth in both the short
      and long term in a number of dysmorphic syndromes, including Turner syndrome. As
      this condition shares many clinical features with Noonan syndrome, it would seem
      logical to treat the latter group with GH. AIMS: To assess the short and long
      term response to GH therapy in patients with Noonan syndrome. METHODS: Analysis
      of patients with Noonan syndrome in the Pharmacia & Upjohn International Growth
      Study (this post-marketing database contains data on the majority of patients
      currently treated with GH in the UK). A questionnaire was also sent to
      participating clinicians. RESULTS: Data on 66 patients (54 males) were available
      for study. At the start of GH therapy children were short, compared with both
      normal and Noonan children. During the first year of GH therapy height velocity
      increased from a mean of 4.9 to 7.2 cm per year. For patients treated long term
      with GH, mean height SDS increased from -2.9 pretreatment to -2.6 after one year
      and -2.3 after five years. Of the 10 patients at near final height, only one had
      a height above the 3rd centile for normal adults and above the mean for untreated
      Noonan patients. The mean increment in final height was 3.1 cm (range -1.1 to 6.5
      cm). CONCLUSIONS: GH therapy in patients with Noonan syndrome will improve height
      velocity in the short term. Longer-term therapy results in a waning of effect;
      initial indications are that final height is not improved substantially in most
      patients.

PMID- 11316697
TI  - Uses of stable isotopes in clinical diagnosis and research in the paediatric
      population.

PMID- 11316701
TI  - Myopia: was mother right about reading in the dark?

PMID- 11316702
TI  - Evolving pathophysiological paradigms for age related macular degeneration.

PMID- 11316703
TI  - Professionally led regulation in medicine.

PMID- 11316704
TI  - Prevention strategies for age related cataract: present limitations and future
      possibilities.

PMID- 11316706
TI  - Myopia and night lighting in children in Singapore.
AB  - AIM: To examine the role of night time lighting and myopia in children in
      Singapore METHODS: A cross sectional study was conducted on 1001 children in two
      Singapore schools. Cycloplegic refraction and A-scan biometry measurements were
      made in both eyes. A detailed questionnaire was completed by the parents to
      obtain information on night time lighting, near work activity, educational and
      demographic factors. RESULTS: There was no difference in myopia prevalence rates
      in children exposed to night time light (33.1%) compared with children who slept
      in the dark (31.4%) before age 2. In addition, vitreous chamber depth was not
      related to night light (p = 0.58) before age 2. These results remained even after
      controlling for near work. CONCLUSION: Myopia is not associated with night light
      in Asian populations.

PMID- 11316705
TI  - Myopia in Singapore: taking a public health approach.

PMID- 11316707
TI  - Factors affecting pulsatile ocular blood flow in normal subjects.
AB  - BACKGROUND: The factors that influence pulsatile ocular blood flow (POBF) were
      evaluated in normal subjects. METHODS: POBF was measured in 80 normal subjects
      using Langham OBF computerised tonometry. The effect of age, systolic and
      diastolic blood pressure, refractive error, intraocular pressure, and axial
      length on POBF was evaluated using multiple regression analysis. RESULTS: The
      mean (SD) POBF value was 593.3 (203.6) microl/min (range 290.7-1201.6). Of all
      the independent variables in the model, only the axial length was statistically
      significant (p = 0.008). The regression coefficient was negative, indicating that
      the axial length decreased with increasing POBF. CONCLUSIONS: These data suggest
      that, in normal subjects, the POBF decreases as axial length increases. Choroidal
      blood flow may decrease as the axial length increases. The axial length may
      therefore be a major factor affecting POBF.

PMID- 11316708
TI  - Pulsatile ocular blood flow study: decreases in exudative age related macular
      degeneration.
AB  - BACKGROUND: Pulsatile ocular blood flow (POBF) is a parameter for evaluating
      choroidal blood flow. POBF in the patients with non-exudative and exudative age
      related macular degeneration (AMD) was investigated. METHODS: POBF, pulse
      amplitude (PA), systolic and diastolic blood pressures, intraocular pressure
      (IOP), refractive error, and axial length were compared among 10 patients with
      non-exudative AMD, 11 patients with exudative AMD, and 69 age matched controls. A
      Langham OBF computerised tonometer was used with the participants in the sitting
      position to measure POBF and PA. RESULTS: No significant differences were found
      in age, systolic and diastolic blood pressures, IOP, or refractive error between
      patients with exudative and non-exudative AMD and the control subjects. In the
      patients with exudative AMD the POBF (median, 372.7 microl/min) and PA (median,
      1.2 mm Hg) were significantly lower than in the patients with non-exudative AMD
      (median, 607.0 microl/min (p = 0.02) and 2.2 mm Hg (p = 0.04), respectively) and
      control subjects (median, 547.4 microl/min (p = 0.01) and 2.0 mm Hg (p = 0.01),
      respectively). CONCLUSIONS: These data show that the POBF and PA in the patients
      with exudative AMD are lower than in the patients with non-exudative AMD and
      normal subjects. Decreased choroidal blood flow may have a role in the
      development of choroidal neovascularisation in AMD.

PMID- 11316709
TI  - Corneal irregular astigmatism after laser in situ keratomileusis for myopia.
AB  - AIMS: To quantitatively evaluate the changes in corneal irregular astigmatism
      after laser in situ keratomileusis (LASIK) in relation to the amount of laser
      ablation. METHODS: In 189 eyes of 116 patients undergoing LASIK for myopia,
      corneal topography was obtained before and 1 month after surgery. Using Fourier
      harmonic analysis of the topography data, corneal irregular astigmatism
      (asymmetry and higher order irregularity) was calculated. RESULTS: By surgery,
      asymmetry component significantly increased (p < 0.0001, Wilcoxon signed rank
      test), while higher order irregularity did not (p = 0.767). The increases in the
      asymmetry component significantly correlated with ablation depth (Spearman rank
      correlation coefficient r(s) = 0.440, p < 0.0001). No significant correlation was
      found between changes in higher order irregularity and ablation depth (r(s) =
      0.137, p = 0.074). CONCLUSION: LASIK significantly increases the asymmetry
      component of the cornea which is dependent on the amount of laser ablation.

PMID- 11316710
TI  - A randomised, double masked, clinical trial of high dose vitamin A and vitamin E
      supplementation after photorefractive keratectomy.
AB  - AIM: To evaluate the effect of a high dose vitamin A and E supplementation on
      corneal re-epithelialisation time, visual acuity and haze following
      photorefractive keratectomy (PRK). METHODS: Two groups of 20 patients who
      underwent myopic PRK were supplemented with either 25 000 IU retinol palmitate
      and 230 mg alpha tocopheryl nicotinate or a placebo. Clinical outcomes were
      evaluated up to 360 days. RESULTS: In the vitamin treated group, re
      epithelialisation time was significantly faster (p = 0.029) and haze incidence
      was reduced (p = 0.035), especially for high myopic corrections (p = 0.043). This
      group also reported a significantly better uncorrected visual acuity (p = 0.043).
      CONCLUSIONS: High dose vitamin A and E oral supplementation may accelerate re
      epithelialisation time and may reduce corneal haze formation after PRK.

PMID- 11316711
TI  - Outcome of lens aspiration and intraocular lens implantation in children aged 5
      years and under.
AB  - AIMS: To determine the visual outcome and complications of lens aspiration with
      intraocular lens implantation in children aged 5 years and under. METHODS: The
      hospital notes of all children aged 5 years and under, who had undergone lens
      aspiration with intraocular lens implantation between January 1994 and September
      1998, and for whom follow up data of at least 1 year were available, were
      reviewed. RESULTS: Of 50 children who underwent surgery, 45 were eligible based
      on the follow up criteria. 34 children had bilateral cataracts and, of these, 30
      had surgery on both eyes. Cataract was unilateral in 11 cases; thus, 75 eyes of
      45 children had surgery. Cataracts were congenital in 28 cases, juvenile in 16,
      and traumatic in one case. The median age at surgery was 39 months (range 11-70
      months). Follow up ranged from 12-64 months (median 36 months). Of 34 children
      with bilateral disease, 25 (73.5%) had a final best corrected visual acuity of
      6/12 or better, while seven (20.5%) achieved 6/18 or less; in one child the
      vision improved from UCUSUM to CSM but another, who had only one eye operated on,
      was unable to fix or follow with this eye preoperatively or 2 years
      postoperatively. Of 11 children with unilateral cataract, five (45.5%) had a
      final best corrected visual of 6/12 or better, and six (54.5%) 6/18 or less. A
      mild fibrinous uveitis occurred in 20 (28.2%) eyes in the immediate postoperative
      period, but resolved with topical steroids. One child had a vitreous wick
      postoperatively requiring surgical division. Glaucoma, endophthalmitis, or
      retinal detachment have not been observed so far in any patient postoperatively.
      CONCLUSION: From this series the authors suggest that, in children aged 5 years
      and under, lens aspiration with intraocular lens implantation is a safe
      procedure, with a good visual outcome in the short term. Further studies are
      needed to investigate these outcomes in the long term.

PMID- 11316712
TI  - Silicone oil-intraocular lens interaction: which lens to use?
AB  - AIM: To determine a suitable intraocular lens for implantation in patients at
      high risk of lens exposure to silicone oil in their lifetime. METHODS: PMMA,
      AcrySof, AR40, AQUA-Sense, and Raysoft lenses were examined. Each lens was
      immersed for 5 minute intervals in balanced salt solution (BSS), in stained
      silicone oil, and again in BSS before being photographed in air and in BSS.
      Percentage silicone oil coverage of the lens optic was determined. RESULTS: The
      mean percentage coating (MPC) for the lens biomaterials ranged from 5.2% to
      21.5%. The Raysoft lens had significantly less oil coverage when statistically
      compared with the other lens types (p < 0.001). CONCLUSION: A Raysoft (Rayner)
      lens is a suitable lens for implantation in patients who are at risk of severe
      vitreoretinal disease.

PMID- 11316713
TI  - Primary rhegmatogenous retinal detachment: 20 years of change.
AB  - AIM: To compare characteristics, management, and outcome of two groups of
      patients with primary rhegmatogenous retinal detachment (RRD) presenting to the
      same vitreoretinal unit approximately 20 years apart. METHODS: 124 patients in
      1979-80 and 126 cases in 1999 were compared. RESULTS: More cases were
      pseudophakic and fewer aphakic in 1999 than 1979-80. More cases of giant retinal
      tear and fewer dialyses were operated on in 1999. Vitrectomy was a primary
      procedure in 63% of cases in 1999 but only 1% in 1979-80. Anatomical success
      rates were statistically similar: 79.8% primary and 88.8% final success in 1979
      80, and 84% primary and 93.6% final success in 1999. CONCLUSION: Surgical
      management of primary RRD has changed greatly in 20 years. Success rates have
      changed little, despite availability of differing surgical techniques.

PMID- 11316714
TI  - Peripheral visual field defects after macular hole surgery: a complication with
      decreasing incidence.
AB  - AIM: To prospectively evaluate peripheral visual fields after vitrectomy for
      idiopathic macular holes. METHODS: Goldmann perimetry was performed in 105
      patients before, as well as 6 weeks and 12 months after macular hole surgery.
      RESULTS: Only one patient (< 1%) with a stage III macular hole developed an
      asymptomatic postoperative visual field defect. The scotoma was wedge-shaped,
      peripherally located in the temporal quadrant, and remained unchanged during the
      following 12 months. CONCLUSION: Peripheral visual field defects after macular
      hole surgery can be a complication of very low incidence. A rather low pressure
      set during air-fluid exchange as well as special aspects of the surgical
      technique may be responsible for this low incidence of peripheral visual field
      defects.

PMID- 11316716
TI  - The rhomboid flap in medial canthal reconstruction.
AB  - AIM: To describe a series of patients who have undergone a medial canthal
      reconstruction with a rhomboid flap. METHODS: A non-comparative interventional
      case series of 27 patients with medial canthal defects after Mohs excision of
      medial canthal basal cell carcinomas who underwent reconstruction using a
      rhomboid-shaped transpositional flap of adjoining skin and subcutaneous tissue.
      25 cases were performed under local anaesthesia. The remaining two cases were
      combined with major lid reconstruction and performed under general anaesthesia.
      The outcome measures were closure of the defect, the cosmetic result,
      complications, and re-operations. RESULTS: Primary closure of the defect was
      achieved in all cases. The cosmetic result was highly satisfactory in all cases.
      There were no major complications or re-operations. Two cases had minor webbing
      of the medial upper lid. CONCLUSIONS: The rhomboid flap is an effective, quick,
      and simple technique for medial canthal reconstruction. It provides excellent
      cosmesis and is associated with minimal complications. It can be modified
      according to the nature of the periorbital skin and the location, size, and depth
      of the defect.

PMID- 11316715
TI  - Detection of Borrelia burgdorferi DNA in urine of patients with ocular Lyme
      borreliosis.
AB  - AIM: To evaluate the diagnostic value of the polymerase chain reaction (PCR) to
      detect Borrelia burgdorferi DNA in patients with ocular Lyme borreliosis.
      METHODS: Of 256 consecutive uveitis patients six selected individuals with
      clinical evidence for Lyme borreliosis and 30 patients with non-Lyme uveitis were
      enrolled. Lyme serology was performed by ELISA and western blotting. Urine
      samples were examined by an optimised nested polymerase chain reaction (PCR)
      protocol. RESULTS: Only four of six uveitis patients suspected for Lyme
      borreliosis were ELISA positive, while all six subjects showed a positive western
      blot. B burgdorferi PCR was positive in all of these six patients. Whereas two of
      the 30 controls had a positive Lyme serology, B burgdorferi DNA was not
      detectable by PCR in any sample from these patients. CONCLUSIONS: PCR for the
      detection of B burgdorferi DNA in urine of uveitis patients is a valuable tool to
      support the diagnosis of ocular Lyme borreliosis. Moreover, these patients often
      show a weak humoral immune response which may more sensitively be detected by
      immunoblotting.

PMID- 11316717
TI  - Psychiatric sequelae and psychosocial adjustment following ocular trauma: a
      retrospective pilot study.
AB  - AIMS: To identify the prevalence of psychiatric and adjustment problems after
      ocular trauma and those factors related to a poor outcome. METHODS: 47 patients
      were assessed by structured interview, of whom 45 satisfactorily completed three
      standardised self report measures of psychological functioning, subjective
      distress, and social adjustment. RESULTS: 33% of patients displayed psychiatric
      "caseness". A number of features of the victim consistently resulted in poor
      outcome including a psychiatric history and peritraumatic dissociation.
      CONCLUSION: These preliminary findings suggest ocular trauma is associated with
      psychomorbidity and problems of adjustment. The improved management of such
      patients would benefit from a more detailed analysis by means of a longitudinal
      study involving larger samples.

PMID- 11316718
TI  - Mosaicking and enhancement of slit lamp biomicroscopic fundus images.
AB  - AIMS: To process video slit lamp biomicroscopic fundus image sequences in order
      to generate wide field, high quality fundus image montages which might be
      suitable for photodocumentation. METHODS: Slit lamp biomicroscopic fundus
      examination was performed on human volunteers with a contact or non-contact lens.
      A stock, charge coupled device camera permitted image capture and storage of the
      image sequence at 30 frames per second. Acquisition time was approximately 30
      seconds. Individual slit lamp biomicroscope fundus image frames were aligned and
      blended with custom developed software. RESULTS: The developed algorithms allowed
      for highly accurate alignment and blending of partially overlapping slit lamp
      biomicroscopic fundus images to generate a seamless, high quality, wide field
      montage. CONCLUSIONS: Video image acquisition and processing algorithms allow for
      mosaicking and enhancement of slit lamp biomicroscopic fundus images. The
      improved quality and wide field of view may confer suitability for inexpensive,
      real time photodocumentation of disc and macular abnormalities.

PMID- 11316720
TI  - Famciclovir for ophthalmic zoster: a randomised aciclovir controlled study.
AB  - AIMS: To compare the efficacy and safety of famciclovir with aciclovir for the
      treatment of ophthalmic zoster. METHODS: Randomised, double masked, aciclovir
      controlled, parallel group in 87 centres worldwide including 454 patients with
      ophthalmic zoster of trigeminal nerve (V(1)) comprised the intent to treat
      population. Oral famciclovir 500 mg three times daily or oral aciclovir 800 mg
      five times daily for 7 days. Assessments included day 0 (screening), days 3 and 7
      (during treatment), days 10, 14, 21, 28 and monthly thereafter, up to 6 months
      (follow up). Proportion of patients who experienced ocular manifestations, severe
      manifestations and non-severe manifestations; loss of visual acuity was the main
      outcome measure. RESULTS: The percentage of patients who experienced one or more
      ocular manifestations was similar for famciclovir (142/245, 58.0%) and aciclovir
      (114/196, 58.2%) recipients, with no significant difference between groups (OR
      0.99; 95% CI 0.68, 1.45). The percentage of patients who experienced severe and
      non-severe manifestations was similar between groups, with no significant
      difference. The prevalence of individual ocular manifestations was comparable
      between groups. There was no significant difference between groups for visual
      acuity loss. CONCLUSION: Famciclovir 500 mg three times daily was well tolerated
      and demonstrated efficacy similar to aciclovir 800 mg five times daily.

PMID- 11316719
TI  - Amniotic membrane transplantation for partial limbal stem cell deficiency.
AB  - AIM: To examine the efficacy, safety, and long term outcomes of amniotic membrane
      transplantation for corneal surface reconstruction in cases of partial limbal
      stem cell deficiency. METHODS: 17 eyes of 15 patients with partial limbal stem
      cell deficiency underwent superficial keratectomy of the conjunctivalised corneal
      surface followed by amniotic membrane transplantation. Cases were followed up for
      at least a year. RESULTS: All eyes exhibited a stable, intact corneal epithelial
      surface after a mean follow up period of 25.8 months with no eyes developing
      recurrent erosion or persistent epithelial defect. The mean time to re
      epithelialisation was 22.8 days. Overall improvement in visual acuity was
      observed in 92.9% of 14 eyes with visual potential. Of those, five eyes gained
      six or more lines, two eyes gained between four and five lines, six eyes gained
      between one and three lines, and one eye lost three lines of Snellen acuity. Pain
      and photophobia were abolished in 86% of cases and substantially reduced in 14%,
      with all eyes exhibiting decreased vascularisation and inflammation at final
      follow up. CONCLUSIONS: Amniotic membrane transplantation appears to be a safe
      and effective method of restoring a stable corneal epithelium for cases of
      partial limbal stem cell deficiency and can be considered as an alternative to
      limbal autograft or allograft.

PMID- 11316721
TI  - Computer modelling of a cataract waiting list.
AB  - AIM: To compare three different strategies for determining admission dates for
      patients awaiting cataract extraction after scoring for visual impairment.
      METHODS: 357 patients attending for assessment for cataract surgery were scored
      for visual impairment. These scores were used as a basis for ranking patients
      into three impairment strata. A computer simulation was used to compare 3 years'
      operation of different admission strategies-a first come first served booking
      system, a triage booking system, and a waiting list system in which admissions
      were strictly ordered according to priority stratum. Differences in priority
      weighted delays before treatment were analysed. RESULTS: Both the triage system
      and the priority based waiting list system gave considerable reduction in
      priority weighted delay compared with a first come first served admission policy.
      The percentage reduction achieved (30%-60%) is strongly influenced by the number
      of weeks fully booked when the booking systems are introduced. The priority
      weighted delay of the triage system, where booking decisions were made at the
      time of the outpatient assessment, was consistently and substantially
      outperformed by the priority based waiting list system where the decision to
      allocate an admission date was delayed as long as possible. CONCLUSIONS: There is
      considerable scope for reducing delays to high priority patients if simple rules
      are used to determine admission dates. Using these rules, booking patients at the
      time of the outpatient assessment gives substantially less benefit in terms of
      reducing delays to high priority patients than if the decision about the
      admission date is deferred.

PMID- 11316722
TI  - Discrimination between normal and glaucomatous eyes with visual field and
      scanning laser polarimetry measurements.
AB  - AIM: To evaluate the ability of structural parameters (as determined by retinal
      nerve fibre layer (RNFL) measurements obtained with the scanning laser
      polarimeter (SLP-NFA/GDx)) and functional parameters (as determined by automated
      perimetry) to discriminate between normal and glaucomatous eyes. METHODS: In a
      case-control study, a total of 91 normal subjects and 94 patients with glaucoma
      underwent automated perimetry and RNFL measurements obtained with the SLP. Three
      independent scans of each eye were obtained and a mean image was created and used
      for further analysis. Only one eye per individual was randomly included in the
      study. The sensitivity (Se) and specificity (Sp) of 12 RNFL parameters were
      calculated according to the SLP internal normative database. The Se and Sp of the
      visual field (VF) global indices and the glaucoma hemifield test (GHT) were also
      calculated according to the instrument's normative database. Receiver operator
      characteristic (ROC) curves were built for each SLP parameter and VF index.
      Fisher's linear discriminant formulas (LDFs) were developed for VF indices (VF
      LDF), SLP measurements (SLP LDF), and both examinations (combined LDF). RESULTS:
      According to the SLP internal database, the parameters with better Se and Sp
      were: superior/nasal ratio (Se = 58.5%; Sp = 86.8%), and GDx the number (Se =
      43.3%; Sp = 96.7%). The construction of an ROC curve for the number resulted in
      Se = 84% and Sp = 79%. The creation of LDFs improved both the sensitivities and
      specificities when compared with isolated parameters SLP LDF (Se = 90.4%; Sp =
      82.4%), VF LDF (Se = 89.4%; Sp = 89.0%), and combined LDF (Se = 93.0%; Sp =
      90.1%). The sensitivity to diagnose early and moderate glaucomatous damage
      observed with the GHT was lower than that obtained with the number (p < 0.01).
      CONCLUSIONS: Creation of LDFs enhanced the Se and Sp for both VF and SLP.
      Integration of SLP and VF in a combined LDF reached the highest Se/Sp relation,
      suggesting that these examinations may be additive concerning the diagnosis of
      glaucoma. The SLP parameter the number may be more sensitive than the GHT in
      diagnosing early and moderate glaucomatous damage.

PMID- 11316723
TI  - Passive permeability and outward active transport of fluorescein across the blood
      retinal barrier in early ARM.
AB  - AIM: To study the passive and active transport of fluorescein across the blood
      retina barrier in early age related maculopathy (ARM) (soft drusen > 63 microm,
      hyperpigmentation and/or hypopigmentation in patients above 50 years of age).
      METHODS: 15 patients and 10 healthy subjects were included. Morphological changes
      were graded from 30 degrees fundus photographs using a simplified version of the
      epidemiological ARM study group classification system. Differential vitreous
      spectrofluorophotometry was used to assess the transport properties of the blood
      retina barrier (that is, passive permeability and unidirectional permeability
      caused by outward active transport from the vitreous to the blood). RESULTS: The
      passive permeability of the patient group was not significantly different from
      that of the control group. Four patients with passive permeability more than 3 SD
      above the mean of the control group (mean 1.8 (SD 0.7) nm/s, range 1.0-3.0 nm/s,
      data normally distributed) all had centrally located drusen > 500 microm and
      superjacent pigment clumps of 63-500 microm in diameter. There was no significant
      difference between the unidirectional permeabilities for the patient group and
      for the control group (mean 47.4 (29.3) nm/s, range 12.7-91.1 nm/s). CONCLUSION:
      There was no significant difference in the passive permeability and in the
      unidirectional permeability of fluorescein. However, the study may indicate that
      the combination of very large drusen and superjacent pigment clumps in ARM may be
      associated with a deterioration of the blood-retina barrier.

PMID- 11316724
TI  - Major orbital complications of endoscopic sinus surgery.
AB  - BACKGROUND: The paranasal sinuses are intimately related to the orbit and
      consequently sinus disease or surgery may cause severe orbital complications.
      Complications are rare but can result in serious morbidity, the most devastating
      of which is severe visual loss. METHODS: A retrospective review was undertaken of
      four cases of severe orbital trauma during endoscopic sinus surgery. RESULTS: All
      the cases suffered medial rectus damage, one had additional injury to the
      inferior rectus and oblique, and two patients were blinded as a result of direct
      damage to the optic nerve or its blood supply. CONCLUSION: Some ophthalmic
      complications of endoscopic sinus surgery are highlighted, the mechanisms
      responsible are discussed, and recommendations for prevention, early recognition,
      and management are proposed.

PMID- 11316725
TI  - The long term outcome of limbal allografts: the search for surviving cells.
AB  - BACKGROUND/AIMS: Limbal allotransplantation is increasingly being used for ocular
      surface repair in patients with limbal stem cell dysfunction. However, it is
      uncertain whether donor cells survive long term on the ocular surface and whether
      patients maintain the early benefits of the procedure. The aims of this study
      were to investigate the long term outcome of clinical limbal allografts and to
      correlate outcome with donor cell survival. METHODS: Five patients who had
      undergone allotransplantation-four keratolimbal allografts and one
      tarsoconjunctival allograft-from 3-5 years previously, and for whom residual
      frozen donor ocular tissue was available, were reviewed. Survival of donor cells
      lifted from the recipient ocular surface by impression cytology was investigated
      by DNA fingerprinting using primers detecting variable nucleotide tandem repeat
      sequences. Recipient buccal cells and scleral samples from the remnant donor eye
      were used to genotype recipients and donors, respectively. Polymerase chain
      reaction products were sized by Genescan analysis. RESULTS: An objective long
      term benefit from the procedure (improved Snellen acuity, reduced frequency of
      epithelial defects, reduced vascularisation, and scarring) was recorded for four
      patients. Some subjective benefit was also reported. However, in no instances
      were donor cells recovered from the ocular surface at 3-5 years post-graft.
      Initial experiments to examine sensitivity indicated that any surviving donor
      cells must have constituted less than 2.5% of cells sampled. CONCLUSION: Limbal
      stem cell allotransplantation can provide long term benefits, as measured by
      objective criteria. However, such benefits do not necessarily correlate with
      survival of measurable numbers of donor cells on the ocular surface.

PMID- 11316726
TI  - Trehalose protects corneal epithelial cells from death by drying.
AB  - AIM: This study was designed to examine whether trehalose could protect corneal
      epithelial cells in culture from death by desiccation in order to test trehalose
      as a potential new eye drop for dry eye syndrome. METHODS: Human corneal
      epithelial cells in near confluent culture in wells of a 96 well multidish were
      preincubated for 15 minutes with 2, 20, 50, 100, or 200 mM trehalose or maltose
      in phosphate buffered saline (PBS), PBS alone, or three kinds of commercially
      available artificial tear substitutes (one with borate buffered saline and the
      other two containing either hydroxyethylcellulose or hyaluronan). The medium was
      aspirated completely and cells were left dry for 30 minutes at room temperature
      in room humidity. Live cells and dead cells were visualised by fluorescent dyes
      and counted for statistical analysis. RESULTS: The percentage of dead corneal
      epithelial cells after desiccation was significantly lower in preincubation with
      50, 100, and 200 mM trehalose, compared with preincubation with PBS alone (p <
      0.0001, Kruskal-Wallis test, and p < 0.05, Tukey-Kramer test). Trehalose at the
      concentration of 20 mM or lower, maltose at any concentrations, and commercially
      available artificial tear substitutes did not protect corneal epithelial cells
      from death by desiccation. CONCLUSIONS: Trehalose at 50, 100, and 200 mM
      protected corneal epithelial cells in culture from death by desiccation.
      Trehalose could be used as a potential new eye drop for dry eye syndrome.

PMID- 11316727
TI  - Apoptosis mediates decrease in cellularity during the regression of Arthus
      reaction in cornea.
AB  - BACKGROUND/AIMS: The Arthus type allergic reaction is characterised by
      inflammatory cell infiltration and marked neovascularisation in the cornea.
      During the healing stages, inflammatory cells and newly formed microvessels
      gradually disappear. The aim was to establish whether apoptosis affected the
      regression of inflammatory cells and newly formed microvessels, in order to
      define more clearly the cellular mechanisms involved in the pathobiology of
      corneal diseases. METHODS: Albino male rabbits were injected subcutaneously with
      5 mg/ml bovine serum albumin (BSA) incorporated in Freund's complete adjuvant
      twice weekly. Under the anaesthesia, 30 microl of a 0.5 mg/ml BSA solution was
      injected into the central corneal stroma to induce an Arthus type allergic
      reaction. The injured corneas were collected at various time points ranging from
      3 to 20 days. Apoptotic cells were identified by both light microscopy using in
      situ TdT-dUTP nick end labelling (TUNEL) method and electron microscopy. RESULTS:
      With increasing time after induction of the Arthus reaction, marked
      neovascularisation and infiltrated inflammatory cells such as polymorphonuclear
      cells (PMNs) and plasma cells were observed in the cornea. Thereafter, the
      inflammatory cells and newly formed microvessels gradually disappeared.
      Coincidently, the numbers of microvessel endothelial cells and infiltrated
      inflammatory cells undergoing apoptosis were increased. Apoptotic bodies were
      taken up by macrophages, PMNs, as well as myofibroblasts derived presumably from
      transformation of migrated keratocytes. CONCLUSIONS: These data demonstrate that
      regression of the cellular infiltrates and microvessel endothelial cells
      associated with the Arthus reaction in the cornea occurs via apoptosis. This
      finding adds insights into the cellular mechanisms regulating the pathobiology of
      corneal diseases.

PMID- 11316728
TI  - Is a one eyed racing driver safe to compete? Formula one (eye) or two?

PMID- 11316729
TI  - Minireview: tissue-specific versus generalized gene targeting of the igf1 and
      igf1r genes and their roles in insulin-like growth factor physiology.
AB  - The insulin-like growth factors (IGF-I and IGF-II) and the IGF-I receptor are
      critically important for normal growth and development of the organism. Gene
      deletion of these elements has demonstrated that IGF-I is important for both
      prenatal and postnatal development, whereas IGF-II is important during prenatal
      stages only. The IGF-I receptor gene-deleted mouse dies at birth apparently as a
      result of poor muscular development. Utilizing the conditional gene-deletion
      approach, we have demonstrated that mice lacking the liver IGF-I gene have an
      approximately 80% reduction in circulating total IGF-I levels. Despite this
      marked reduction, postnatal growth and development was normal, suggesting that
      liver IGF-I is not essential for this function. Local tissue IGF-I production was
      unaffected and may compensate for the lack of the liver IGF-I. Further studies
      are ongoing to establish the role of the endocrine vs. the autocrine/paracrine
      IGF-I.

PMID- 11316730
TI  - Editorial: nutrition, glucocorticoids, birth size, and adult disease.

PMID- 11316731
TI  - Maternal undernutrition during late gestation induces fetal overexposure to
      glucocorticoids and intrauterine growth retardation, and disturbs the hypothalamo
      pituitary adrenal axis in the newborn rat.
AB  - As fetal overexposure to glucocorticoids has been postulated to induce
      intrauterine growth retardation (IUGR) in humans, we investigated the effects of
      maternal 50% food restriction (FR50) in rats during the last week of gestation on
      the hypothalamo-pituitary adrenal (HPA) axis activity in both mothers and their
      fetuses. In mothers, FR50 increased both the plasma corticosterone (B) level from
      embryonic days 19-21 and the relative adrenal weight at term. FR50 decreased at
      term both the maternal plasma corticosteroid-binding globulin level and placental
      11beta-hydroxysteroid dehydrogenase type 2 expression. In newborns, maternal FR50
      reduced body and adrenal weights, glucocorticoid and mineralocorticoid receptor
      expressions in the hippocampus, corticoliberin expression in the hypothalamic
      paraventricular nucleus, and plasma ACTH. In FR50 newborns, the plasma B level
      was increased at birth and decreased 2 h later. When maternal circulating B was
      maintained at the basal level by adrenalectomy and B supply, FR50 induced IUGR in
      pups and decreased placental 11beta- hydroxysteroid dehydrogenase type 2
      expression at term, but did not disturb the offspring's HPA axis. These results
      suggest that maternal undernutrition during late gestation induces both IUGR and
      an overexposure of fetuses to maternal B, which disturb the development of the
      HPA axis.

PMID- 11316732
TI  - Analysis of homogeneous populations of anterior pituitary folliculostellate cells
      by laser capture microdissection and reverse transcription-polymerase chain
      reaction.
AB  - Pituitary folliculostellate (FS) cells are usually located between the secretory
      cells in the anterior pituitary, and they produce many peptides that exert a
      paracrine effect on hormone-producing pituitary cells. Previous approaches have
      been unsuccessful in obtaining homogeneous populations of FS cells. We used a
      combination of immunostaining with S100 protein followed by laser capture
      microdissection (Immuno-LCM) to obtain purified populations of rat FS cells.
      These cells were analyzed along with a mouse FS cell line (TtT/GF) by RT-PCR for
      gene expression. RT-PCR analyses showed that both FS cell populations expressed
      the mRNAs for glial fibrillary acidic protein, S100 protein, transforming growth
      factor-beta1 (TGFbeta1), TGFbeta receptor, interleukin-6, leptin, leptin
      receptor, pituitary adenylate cyclase-activating polypeptide (PACAP), and PACAP
      receptors. Both FS cell populations were negative for PRL, GH, and POMC,
      supporting the homogeneity of the rat FS cell population. TGFbeta1, but not PACAP
      38, treatment stimulated cell proliferation in both FS cell populations. TGFbeta1
      increased leptin, but not interleukin-6, mRNA expression in rat FS cells.
      However, TGFbeta1 inhibited leptin RNA expression in the TtT/GF cell line, as
      shown by RT-PCR and Northern blot analysis. These results indicate that 1)
      homogeneous populations of FS cells can be prepared by Immuno-LCM; 2) TGFbeta1
      stimulates the proliferation of normal rat FS cells and the TtT/GF cell line; and
      3) the effects of TGFbeta1 to stimulate leptin mRNA expression in rat FS cells
      but inhibit leptin mRNA expression in TtT/GF cells probably reflect alterations
      in signal transduction in the TtT/GF cell line.

PMID- 11316733
TI  - The role of phosphatidylinositol 3-kinase and the mitogen-activated protein
      kinases in insulin-like growth factor-I-mediated effects in vascular endothelial
      cells.
AB  - Despite an improved understanding of the molecular mechanisms of insulin-like
      growth factor-I (IGF-I) signaling and the recognition that IGF-I mediates many
      effects in endothelial cells, some of which may be important for atherosclerosis,
      little is known about the signal transduction pathways that mediate the effects
      of IGF-I in endothelial cells. To that end, we examined the signaling pathways
      activated by IGF-I in endothelial cells and their contribution to IGF-I
      stimulated endothelial cell migration and nuclear factor (NF)-kappaB-dependent
      transcription. Treatment of bovine pulmonary artery endothelial cells (PAEC) with
      IGF-I activated the mitogen-activated protein kinases extracellular signal
      regulated kinase (ERK)1/2 and ERK5. In contrast, IGF-I had no effect on either c
      Jun amino-terminal kinase or p38 kinase activity. IGF-I also activated
      phosphatidylinositol (PI) 3-kinase, as reflected by increased phosphorylation of
      AKT: There was no evidence of cross-talk between the ERK and PI 3-kinase pathways
      in PAEC. In PAEC transiently transfected with pTK81-NFkappaB-Luc, which contained
      four copies of the NF-kappaB DNA binding site 5' to a minimal promoter and the
      luciferase gene, treatment with 50 ng/ml IGF-I increased luciferase activity 1.8
      fold. Inhibition of ERK activity using PD98059 and PI 3-kinase activity with LY
      294002 abrogated the induction of NF-kappaB-dependent transcription by IGF-I,
      suggesting that both pathways contribute to the effect of IGF-I on NF
      kappaBdependent transcription. In contrast to the effect of tumor necrosis factor
      alpha on NF-kappaB activation, Western blot analyses demonstrated that IGF-I had
      no effect on IkappaB phosphorylation and degradation or nuclear translocation and
      DNA binding of NF-kappaB. These data suggest a direct of effect of IGF-I on
      nuclear NF-kappaB. IGF-I also increased endothelial cell migration approximately
      2-fold, as demonstrated using a Boyden chamber apparatus. IGF-I-induced
      endothelial cell migration was inhibited, in part, by LY 294002 but not PD98059.
      Together, these studies demonstrate that IGF-I activates multiple signaling
      pathways in endothelial cells with little evidence for cross-talk between the
      pathways. Moreover, these pathways appear to mediate both overlapping and
      distinct effects in that activation of both PI 3-kinase and the ERKs contributed
      to the stimulation of NF-kappaB-dependent transcription by IGF-I, whereas only PI
      3-kinase mediated IGF-I-stimulated endothelial cell migration.

PMID- 11316734
TI  - Dietary phosphorus deprivation induces 25-hydroxyvitamin D(3) 1alpha-hydroxylase
      gene expression.
AB  - Dietary phosphorus deprivation causes hypophosphatemia and an increase in serum
      1alpha,25-dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)] concentrations. To determine
      the molecular mechanisms of this regulation, the effects of dietary phosphorus
      deprivation and hypophysectomy on 25-hydroxyvitamin D(3) 1alpha-hydroxylase
      (1alpha-hydroxylase) protein and messenger RNA (mRNA) expression were examined in
      rats. A low phosphorus diet (LPD) for 4 days resulted in hypophosphatemia and an
      increase in serum 1,25-(OH)(2)D(3) levels. This increase was caused by the
      induction of 1alpha-hydroxylase protein and mRNA expression (4- and 10-fold
      increases, respectively). Administration of the LPD or normal phosphorus diet to
      hypophysectomized (HPX) rats resulted in hypophosphatemia and suppression of
      1alpha-hydroxylase gene expression, indicating that hypophosphatemia itself is
      not sufficient to induce 1alpha-hydroxylase mRNA expression. Administration of GH
      to HPX rats fed LPD could partially restore 1alpha-hydroxylase mRNA expression,
      whereas supplementation with insulin-like growth factor I, T(3), estrogen, or
      corticosterone had no effect. We also examined Phex gene expression in the bone,
      because the clinical features of X-linked hypophosphatemia resemble those of HPX
      rats. Phex mRNA expression, however, was not altered in HPX rats. In conclusion,
      we demonstrated that the increase in serum 1,25-(OH)(2)D(3) levels caused by
      dietary phosphorus deprivation is due to the induction of 1alpha-hydroxylase mRNA
      expression, and this increase is mediated in part by a GH-dependent mechanism.

PMID- 11316735
TI  - Hormonal regulation and differential actions of the helix-loop-helix
      transcriptional inhibitors of differentiation (Id1, Id2, Id3, and Id4) in Sertoli
      cells.
AB  - The testicular Sertoli cells support spermatogenesis by providing a
      microenvironment and structural support for the developing germ cells. Sertoli
      cell functions are regulated by the gonadotropin FSH. Sertoli cells become a
      terminally differentiated nongrowing cell population in the adult. In response to
      FSH, the Sertoli cells express a large number of differentiated gene products,
      such as transferrin, which transports iron to the developing germ cells.
      Previously, members of the basic helix-loop-helix (bHLH) family of transcription
      factors have been shown to influence FSH-mediated gene expression in Sertoli
      cells. The functions of the bHLH proteins are modulated by Id (inhibitor of
      differentiation) proteins, which lack the DNA-binding basic domain. The Id
      proteins form transcriptionally inactive dimers with bHLH proteins and thus
      regulate cell proliferation and differentiation. The current study investigated
      the expression and function of Id proteins in the postmitotic Sertoli cell.
      Freshly isolated and cultured Sertoli cells coexpress all four isoforms of Id
      (Id1, Id2, Id3, and Id4), as determined by immunoprecipitation with isoform
      specific anti-Id antibodies, RT-PCR, and Northern blot analysis. Id2 and Id3
      expression levels seem higher than Id1. Interestingly, the expression of Id4 in
      Sertoli cells is only detectable after stimulation with FSH or cAMP. The Id1
      expression is down-regulated by FSH and cAMP, whereas Id2 and Id3 levels remain
      unchanged in response to FSH. In contrast, serum induces the expression of Id1,
      Id2, and Id3. Treatment of Sertoli cells with serum significantly reduces the
      expression of the larger 4-kb Id4 transcript and promotes the presence of a novel
      1.3-kb transcript of Id4. The regulatory role of FSH in the expression of all
      four isoforms of Id is mimicked by a cAMP analog, suggesting that the actions of
      FSH are mediated through the protein kinase A pathway. An antisense approach was
      used to study the functional significance of Id proteins in Sertoli cells.
      Antisense to Id1 stimulated transferrin promoter activity in a transient
      transfection assay. Interestingly, an antisense to Id2 down-regulated transferrin
      promoter activity. Id3 and Id4 antisense oligonucleotides had no effect on FSH
      mediated transferrin promoter activation. Contrary to the hypothesis that Id
      proteins have redundant functions, the results of the current study suggest that
      Id1, Id2, Id3, and Id4 are differentially regulated and may have distinct
      functions. Id1 may act to maintain Sertoli cell growth potential, whereas Id2 and
      Id4 may be involved in the differentiation and hormone regulation of Sertoli
      cells.

PMID- 11316737
TI  - Proteasomal activation mediates down-regulation of inositol 1,4,5-trisphosphate
      receptor and calcium mobilization in rat pancreatic islets.
AB  - Inositol 1,4,5-trisphosphate receptor (IP3R) protein levels in isolated rat
      pancreatic islets were investigated in response to carbachol (CCh) and sulfated
      cholecystokinin 26-33 amide stimulation. Within 2 h, CCh reduced IP3R-I protein
      levels by 22% and IP3R-II and -III levels to 65% or more below basal. Sulfated
      cholecystokinin 26-33 amide decreased the levels of IP3R-I, -II, and -III by 34%,
      60%, and 66% below basal, respectively. The effect of CCh was concentration- and
      time-dependent, with a persistent decline in IP3R levels for up to 6 h after the
      onset of stimulation. CCh-pretreated islets also showed an inhibition of glucose
      stimulated insulin secretion. Proteasome inhibition completely blocked the down
      regulatory effects of CCh on IP3Rs and significantly increased the insulin
      secretory response to glucose stimulation in the presence of CCH: Islet
      stimulation by glucose, alpha-ketoisocaproic acid, and tolbutamide completely
      protected IP3Rs against the down-regulatory effects of CCH: 2-deoxyglucose and 3
      O-methyl glucose failed to affect CCh-induced IP3R down-regulation. The
      protective effects of glucose on IP3R down-regulation were completely inhibited
      by the Ca(2+) channel-blocking agent nimodipine. Intracellular Ca(2+)
      ([Ca(2+)](i)) levels in Fura-2 (fluorescent Ca(2+) indicator)-loaded islets, in
      the absence of extracellular Ca(2+), increased in response to glucose
      stimulation; but in islets pretreated with CCh, glucose did not increase
      [Ca(2+)](i) above basal levels. However, in islets pretreated with CCh and the
      proteasomal inhibitor MG-132 (carbobenzoxyl-leucinyl-leucinyl-leucinyl-H), the
      glucose-stimulated increase in [Ca(2+)](i) was significantly higher than the
      change observed for glucose-stimulated [Ca(2+)](i) in the absence of MG-132. The
      results suggest that muscarinic receptor stimulation modulates IP3R protein
      levels in islets through a proteasomal activation pathway, and that down
      regulation of IP3Rs has a profound effect on Ca(2+) mobilization in islets that
      may relate to insulin secretory responsiveness.

PMID- 11316736
TI  - Gonadotropin-releasing hormone receptor in the teleost Haplochromis burtoni:
      structure, location, and function.
AB  - GnRH acts via GnRH receptors (GnRH-R) in the pituitary to cause the release of
      gonadotropins that regulate vertebrate reproduction. In the teleost fish,
      Haplochromis burtoni, reproduction is socially regulated through the hypothalamus
      pituitary-gonadal axis, making the pituitary GnRH-R a likely site of action for
      this control. As a first step toward understanding the role of GnRH-R in the
      social control of reproduction, we cloned and sequenced candidate GnRH-R
      complementary DNAs from H. burtoni tissue. We isolated a complementary DNA that
      predicts a peptide encoding a G protein-coupled receptor that shows highest
      overall identity to other fish type I GnRH-R (goldfish IA and IB and African
      catfish). Functional testing of the expressed protein in vitro confirmed high
      affinity binding of multiple forms of GNRH: Localization of GnRH-R messenger RNA
      using RT-PCR revealed that it is widely distributed in the brain and retina as
      well as elsewhere in the body. Taken together, these data suggest that this H.
      burtoni GnRH receptor probably interacts in vivo with all three forms of GNRH:

PMID- 11316738
TI  - Expression of ZAKI-4 messenger ribonucleic acid in the brain during rat
      development and the effect of hypothyroidism.
AB  - We identified ZAKI-4 (also designated as DSCR1L1) as a thyroid hormone responsive
      gene in cultured human skin fibroblasts. Recently it has been reported that ZAKI
      4 belongs to an evolutionary conserved family of proteins that function as
      calcineurin inhibitor. In human, ZAKI-4 and calcineurin are highly expressed in
      brain, where thyroid hormones play essential roles in the development during
      fetal and neonatal periods. In the present study, we examined the temporal and
      spatial expression patterns of ZAKI-4 messenger RNA (mRNA) in control and
      hypothyroid rat brains. Northern blot analysis revealed that ZAKI-4 mRNA was
      detected in both cerebral cortex and cerebellum as early as embryonic day (E)18.
      In the cerebral cortex, the expression level gradually increased with age,
      reaching a plateau at postnatal day (P)7 and remained constant thereafter until
      P30. A similar pattern of increase with age was also observed in hypothyroid
      rats; however, the magnitude of the increase was significantly reduced. In
      control rats, the fold increase in ZAKI-4 mRNA level from E18 to P17 was 10.8;
      whereas in hypothyroid rats, it was 7.4. In cerebellum the expression level did
      not change with age or by thyroid status. In situ hybridization revealed that
      ZAKI-4 mRNA is widely expressed in neurons throughout the brain. It is noteworthy
      that the expression in the neurons of layer VI of the cerebral cortex was more
      evident in control rats than that in hypothyroid rats from P17 to P30. Though not
      influenced by hypothyroidism, there were several regions of the brain in which
      ZAKI-4 mRNA was strongly expressed. These regions were the mitral cell layer of
      the olfactory bulb, the substantia nigra, and the hippocampus, where calcineurin
      is also abundantly expressed. Therefore, it may be hypothesized that ZAKI-4 plays
      an important role in the development and function of the brain by modulating
      calcineurin function; and decrease in ZAKI-4 mRNA expression in the specific
      brain areas may explain, in some parts, the mechanism of abnormal brain
      development by hypothyroidism.

PMID- 11316739
TI  - Advanced glycosylation end products up-regulate connective tissue growth factor
      (insulin-like growth factor-binding protein-related protein 2) in human
      fibroblasts: a potential mechanism for expansion of extracellular matrix in
      diabetes mellitus.
AB  - Expansion of extracellular matrix with fibrosis occurs in many tissues as part of
      the end-organ complications in diabetes, and advanced glycosylation end products
      (AGE) are implicated as one causative factor in diabetic tissue fibrosis.
      Connective tissue growth factor (CTGF), also known as insulin-like growth factor
      binding protein-related protein-2 (IGFBP-rP2), is a potent inducer of
      extracellular matrix synthesis and angiogenesis and is increased in tissues from
      rodent models of diabetes. The aim of this study was to determine whether CTGF is
      up-regulated by AGE in vitro and to explore the cellular mechanisms involved. AGE
      treatment of primary cultures of nonfetal human dermal fibroblasts in confluent
      monolayer increased CTGF steady state messenger RNA (mRNA) levels in a time- and
      dose-dependent manner. In contrast, mRNAs for other IGFBP superfamily members,
      IGFBP-rP1 (mac 25) and IGFBP-3, were not up-regulated by AGE. The effect of the
      AGE BSA reagent on CTGF mRNA was due to nonenzymatic glycosylation of BSA and,
      using neutralizing antisera to AGE and to the receptor for AGE, termed RAGE, was
      seen to be due to late products of nonenzymatic glycosylation and was partly
      mediated by RAGE. Reactive oxygen species as well as endogenous transforming
      growth factor-beta1 could not explain the AGE effect on CTGF mRNA. AGE also
      increased CTGF protein in the conditioned medium and cell-associated CTGF. Thus,
      AGE up-regulates the profibrotic and proangiogenic protein CTGF (IGFBP-rP2), a
      finding that may have significance in the development of diabetic complications.

PMID- 11316740
TI  - Regulation of uterine gamma-aminobutyric acid(A) receptor subunit expression
      throughout pregnancy.
AB  - Uterine contractions at parturition depend upon a variety of factors, including
      gamma-aminobutyric acid (GABA)-ergic stimulation. A new subunit of the GABA(A)
      receptor, pi, has recently been identified as being particularly abundant in the
      rat uterus. Reduced derivatives of progesterone, such as the 3alpha,5alpha
      reduced derivative termed allopregnanolone, modulate GABA(A) receptor activity
      and neuronal inhibition by modulating the frequency and duration of GABA(A)
      channel opening. This modulation depends on the specific subunit composition of
      the GABA(A) receptor. In particular, assembly of recombinant pi and delta GABA(A)
      receptor subunits into a functional GABA(A) receptor have been reported to reduce
      sensitivity to allopregnanolone. As allopregnanolone works through the GABA(A)
      receptor to reduce uterine contraction, we hypothesized that incorporation of the
      pi-subunit into this receptor in the uterus might change the sensitivity of the
      GABA(A) receptor to allopregnanolone and modulate parturition. We therefore
      determined the expression of GABA(A) receptor subunit messenger RNAs (mRNAs) in
      rat uteri from various gestational ages and determined the physiological
      properties of the receptors. GABA(A) pi-subunit mRNA abundance was constant
      throughout gestation, but decreased at the onset of labor. Other GABA(A) subunits
      fluctuated differently during pregnancy: GABA(A) alpha(1)-subunit mRNA expression
      increased, whereas alpha(2)- and delta-subunit mRNA expression decreased during
      pregnancy, and beta(3)-subunit mRNA only appeared on postpartum day 1. We
      determined how allopregnanolone affected the binding of muscimol, a ligand for
      the GABA(A) receptor, to rat uterine GABA(A) receptors throughout pregnancy.
      Allopregnanolone caused the greatest increase in muscimol binding to uterine
      GABA(A) receptors at 19.5 days gestation and the least increase during labor, a
      time when pi and alpha(1) receptor subunit mRNA concentrations were low, and
      delta and alpha(2) receptor subunit mRNA concentrations were high. Thus, the
      subunit composition of the GABA(A) receptor differs in rat uteri throughout
      gestation. These changes may also affect the sensitivity of the GABA(A) receptor
      to allopregnanolone and thus contribute to the regulation of parturition.

PMID- 11316741
TI  - Responses of the fetal pituitary-adrenal axis to acute and chronic hypoglycemia
      during late gestation in the sheep.
AB  - We investigated the response of the fetal pituitary-adrenal axis to acute and
      chronic hypoglycemia before and after the normal prepartum activation of this
      axis at around 135 days gestation (term = 147 +/- 3 days). Pregnant ewes were
      either well nourished (control group; n = 22) or undernourished (UN; 50%
      reduction in maternal nutrient intake; n = 23) during the last 30 days of
      pregnancy. Acute hypoglycemia was induced by intrafetal administration of insulin
      between 125 and 130 days gestation (control, n = 7; UN, n = 12) and between 138
      and 141 days gestation (control, n = 6; UN = 9). Fetal plasma glucose
      concentrations were significantly lower (P < 0.005) in the UN compared with the
      control group throughout the insulin infusion period at both gestational age
      ranges. In the control group, there was no fetal ACTH response to insulin
      infusion before 135 days gestation, but there was a significant (P < 0.001)
      response after 136 days gestation. In the UN group, there was a significant ACTH
      response to insulin infusion both before and after 135 days gestation, and there
      was no difference in the fetal ACTH response between the two gestational age
      ranges. The plasma cortisol responses to insulin were greater (P < 0.001) after
      136 days compared with before 135 days gestation in both the UN and control
      groups. In the control group there was no significant relationship between basal
      fetal plasma ACTH and glucose concentrations between 115-135 days gestation or
      between 136-145 days gestation. In the UN group, fetal glucose ranged from 0.5
      2.0 mM, and plasma ACTH and glucose concentrations were inversely related at 115
      135 days gestation [log ACTH = -0.31 (glucose) + 2.21; r = -0.37; P < 0.001] and
      at 136-145 days gestation [log ACTH = -0.40 (glucose) + 2.50; r = -0.54; P <
      0.001]. When the UN and control groups were combined, fetal plasma ACTH
      concentrations were significantly greater (F = 13.5; P < 0.05) when plasma
      glucose concentrations were less than 1.0 mM at either 115-135 days or 136-147
      days gestation. Similarly, fetal plasma cortisol concentrations were also
      significantly greater (F = 18.7; P < 0.05) when plasma glucose concentrations
      were less than 1.0 mM at each gestational age range. Therefore, there is an
      increased sensitivity of the fetal hypothalamo-pituitary axis to acute falls in
      glucose concentrations below 1.2 mM after 135 days compared with earlier in
      gestation. The fetal hypothalamo-pituitary axis can respond, however, when plasma
      glucose concentrations fall below 1.0 mM, before and after 135 days gestation,
      independently of whether the low glucose concentrations are a consequence of
      insulin-induced hypoglycemia or maternal nutrient restriction.

PMID- 11316742
TI  - Interferon-tau (IFNtau) regulation of IFN-stimulated gene expression in cell
      lines lacking specific IFN-signaling components.
AB  - Interferon-tau (IFNtau) is a unique type I IFN secreted by the ruminant conceptus
      that acts in a paracrine manner on the endometrial epithelium to signal pregnancy
      recognition. In the ovine endometrium, IFNtau suppresses estrogen receptor alpha
      and oxytocin receptor gene expression, but increases or induces expression of IFN
      simulated genes (ISGs), including signal transducer and activator of
      transcription-1 (STAT1), STAT2, ISG factor-3gamma (ISGF3gamma)/p48/IFN regulatory
      factor-9, and 2',5'-oligoadenylate synthetase (OAS). Human fibroblast cell lines
      lacking specific IFN signaling components were employed to determine the roles of
      STAT1, STAT2, and ISGF3gamma in the effects of IFNtau on ISG protein expression.
      Results indicated that STAT1alpha or STAT1beta is required for IFNtau effects on
      STAT2, ISGF3gamma, and OAS (40/46, 69/71, and 100 kDa). STAT2 is required for
      effects on STAT1, ISGF3gamma, and all OAS forms. ISGF3gamma is required for
      effects of IFNtau on STAT2 and 40/46- and 69/71-kDa OAS and plays a role in the
      effects of IFNtau on 100-kDa OAS and STAT1. Mutation of Tyr(701), but not
      Ser(727), of STAT1 abolished the effects of IFNtau on ISG expression. Mutation of
      the SH2 domain of STAT1 abolished the effects of IFNtau on all ISGs and reduced
      increases in 100-kDa OAS. These data illustrate the importance of transcription
      factors composed of STAT1, STAT2, and ISGF3gamma in the signaling pathway
      mediating the effects of IFNtau on ISG expression.

PMID- 11316743
TI  - Coordinated control of fetal gastric epithelial functions by insulin-like growth
      factors and their binding proteins.
AB  - The influence of insulin-like growth factors (IGFs) and their binding proteins
      (IGFBPs) on human gastric functions are unknown. This study was undertaken to
      evaluate the ability of fetal gastric mucosa to produce IGFBPs and to test the
      effects of IGF-I, IGF-II, and synthetic truncated IGFs that do not interact with
      IGFBPs on epithelial cell proliferation and glandular zymogenic function. Western
      blots, Far Western blots, and immunohistochemistry were performed to characterize
      the expression of IGFBP-1 to -6 and IGF-I receptor. The effects of growth factors
      on DNA synthesis and lipase and pepsin activities were determined in gastric
      explants maintained in serum-free organ culture. All gastric epithelial cells
      expressed the IGF-I receptor. IGFBP-2 to -6 were produced endogenously, and they
      were differentially localized along the foveolus-gland axis and modulated in
      culture. Exogenous IGF-I and IGF-II were able to reduce lipase activity without
      affecting pepsin, whereas they exerted different effects on cellular
      proliferation: IGF-I was stimulatory and IGF-II had no influence. Illustrating
      the complex regulatory effect that IGFBPs exert on IGF bioactivity, both
      truncated IGF-I and IGF-II stimulated DNA synthesis more than IGF-I. Moreover,
      the striking difference in mitogenic activity between truncated and native forms
      of IGF-II probably reflects the abundance of IGFBP-2 and IGFBP-6, two IGF-II
      carriers, in the foveolus/neck region, including the proliferative compartment.
      This study provides new evidence for the involvement of an intragastric IGF/IGFBP
      system in the fine regulation of epithelial cell division and also in the control
      of zymogen synthesis. Moreover, the specific influence of IGF-II as a mitogen
      appears to be tightly regulated by IGFBP isoforms preferentially associated with
      this growth factor and proliferative cells.

PMID- 11316744
TI  - Regulation of arylalkylamine N-acetyltransferase-2 (AANAT2, EC 2.3.1.87) in the
      fish pineal organ: evidence for a role of proteasomal proteolysis.
AB  - In fish, individual photoreceptor cells in the pineal organ and retina contain
      complete melatonin rhythm generating systems. In the pike and seabream, this
      includes a photodetector, circadian clock, and melatonin synthesis machinery; the
      trout lacks a functional clock. The melatonin rhythm is due in part to a
      nocturnal increase in the activity of the arylalkylamine N-acetyltransferase
      (AANAT) which is inhibited by light. Two AANATs have been identified in fish:
      AANAT1, more closely related to AANATs found in higher vertebrates, is
      specifically expressed in the retina; AANAT2 is specifically expressed in the
      pineal organ. We show that there is a physiological day/night rhythm in pineal
      AANAT2 protein in the pike, and that light exposure at midnight decreases the
      abundance of AANAT2 protein and activity. In culture, this decrease is blocked by
      inhibitors of the proteasomal degradation pathway. If glands are maintained under
      light at night, treatment with these inhibitors increases AANAT2 activity and
      protein. Organ culture studies with the trout and seabream also indicate that the
      light-induced decrease of AANAT2 activity is prevented when proteasomal
      proteolysis is blocked. A cAMP-dependent pathway protects AANAT2 protein from
      degradation. These results provide a clue to understanding how light regulates
      the daily rhythm in melatonin secretion in fish photoreceptor cells and provides
      evidence that proteasomal proteolysis is a conserved element in the regulation of
      AANAT in vertebrates.

PMID- 11316745
TI  - Role of keratinocyte growth factor in the control of surfactant synthesis by
      fetal lung mesenchyme.
AB  - Fetal lung maturation is regulated by mesenchymal-epithelial cell communication,
      which plays a major role in the control of surfactant synthesis by alveolar type
      II cells. We have recently shown that keratinocyte growth factor (KGF), also
      called fibroblast growth factor-7, enhances the maturation of fetal alveolar
      epithelial type II cells. Here, we investigated, among the factors produced by
      lung mesenchyme, the part attributable to KGF in the control of surfactant
      synthesis. Using a KGF-neutralizing antibody, we assessed surfactant phospholipid
      synthesis by measuring choline incorporation into disaturated phosphatidylcholine
      of isolated fetal type II cells. We found that KGF accounts for about half of the
      stimulating activity present in fetal lung fibroblast-conditioned medium (FCM).
      By contrast, the use of an epidermal growth factor-neutralizing antibody did not
      alter the FCM-stimulating activity. To further delineate KGF properties as a
      mesenchymal mediator, we wondered about its possibility to relay glucocorticoid
      stimulating activity on the synthesis of the phospholipid moiety of surfactant in
      fetal lung fibroblasts. A 24-h exposure to dexamethasone led us to detect a 50%
      increase in the level of KGF messenger RNA (mRNA) in isolated fetal lung
      fibroblasts. Moreover, anti-KGF antibody totally abolished the further increase
      of FCM-stimulating activity induced by dexamethasone. Thus, KGF seems to be a
      major player in mediating glucocorticoid stimulation of fetal lung maturation.

PMID- 11316746
TI  - Glucagon-like peptide-1 causes pancreatic duodenal homeobox-1 protein
      translocation from the cytoplasm to the nucleus of pancreatic beta-cells by a
      cyclic adenosine monophosphate/protein kinase A-dependent mechanism.
AB  - Glucagon-like peptide-1 (GLP-1) enhances insulin secretion and synthesis. It also
      regulates the insulin, glucokinase, and GLUT2 genes. It mediates increases in
      glucose-stimulated insulin secretion by activating adenylyl cyclase and elevating
      free cytosolic calcium levels in the beta-cell. In addition, GLP-1 has been
      shown, both in vitro and in vivo, to be involved in regulation of the
      transcription factor, pancreatic duodenal homeobox-1 protein (PDX-1), by
      increasing its total protein levels, its translocation to the nucleus and its
      binding and resultant increase in activity of the insulin gene promoter in beta
      cells of the pancreas. Here we have investigated the role of protein kinase A
      (PKA) in these processes in RIN 1046-38 cells. Three separate inhibitors of PKA,
      and a cAMP antagonist, inhibited the effects of GLP-1 on PDX-1. Furthermore,
      forskolin, (which stimulates adenylyl cyclase and insulin secretion), and 8-Bromo
      cAMP, (an analog of cAMP which also stimulates insulin secretion), mimicked the
      effects of GLP-1 on PDX-1. These effects were also prevented by PKA inhibitors.
      Glucose-mediated increases in nuclear translocation of PDX-1 were not prevented
      by PKA inhibitors. Our results suggest that regulation of PDX-1 by GLP-1 occurs
      through activation of adenylyl cyclase and the resultant increase in
      intracellular cAMP, in turn, activates PKA, which ultimately leads to increases
      in PDX-1 protein levels and translocation of the protein to the nuclei of beta
      cells.

PMID- 11316747
TI  - Expression and functional role of hepatocyte growth factor receptor (C-MET)
      during postnatal rat testis development.
AB  - The met protooncogene encodes the hepatocyte growth factor receptor (HGFR, c
      met). C-met, a tyrosine kinase receptor protein, is widely expressed in different
      cell types including the male reproductive tract. As we recently demonstrated,
      both c-met messenger RNA and protein are expressed in prebuberal rat testis. The
      aim of this work was to detect the expression of c-met during postnatal testis
      development and to study its functional role. Our findings show that in total rat
      testis c-met is expressed during postnatal life until the sexual maturation of
      the animals. To evaluate the receptor expression in the different cell types in
      the testis, homogeneous cell populations of Sertoli and peritubular myoid cells
      were isolated from the seminiferous tubules of 10- and 35-day-old animals. c-met
      gene is expressed in myoid cells at the ages considered and its expression
      decreases with increasing age. By contrast, in Sertoli cells c-met expression is
      first detectable at 25 days of life and its expression increases with the
      increasing age being well evident at 35 days of age. C-met protein was detected
      by immunocytochemistry and its expression correlates with gene expression. The
      receptor is functionally active because HGF administration induces morphological
      changes in myoid cells and in c-met-expressing Sertoli cells. As a consequence of
      HGF addition, Sertoli cells cultured on reconstituted basement membrane
      reorganize into cord-like structures that resemble testicular seminiferous cords.
      The data here reported demonstrate for the first time that in Sertoli cells c-met
      expression is developmentally regulated being present and functionally active in
      postpuberal Sertoli cells. Given that c-met expression persists in myoid cells
      during postnatal testis development and that in Sertoli cells its expression
      correlates over time with germ cell differentiation and lumen formation, we
      conclude that the c-met/HGF system is involved in testis development and
      function.

PMID- 11316748
TI  - The insulin-like growth factor I receptor-induced interaction of insulin receptor
      substrate-4 and Crk-II.
AB  - Stimulation of the insulin or insulin-like growth factor (IGF)-I receptor results
      in activation of several signaling pathways. Proteins of the insulin receptor
      substrate (IRS) family play important roles in mediating these signaling
      cascades. To date, four members of the IRS family of docking proteins have been
      characterized. Recently, we have reported that stimulation of the IGF-I receptor
      in 293 HEK cells regulates interaction of the newly discovered IRS-4 molecule
      with the Crk family of proteins. In the present study, we characterize the
      molecular basis of these interactions. C- and N termini truncation analysis of
      IRS-4 demonstrated that the region between amino acids 678 and 800 of the IRS-4
      molecule is involved in this interaction. This region contains a cluster of four
      tyrosines (Y(700), Y(717), Y(743), and Y(779)). We hypothesize that one or more
      of these tyrosines are involved in the interaction between the SH2 domain of the
      Crk-II molecule when IRS-4 is phosphorylated upon IGF-I receptor activation.
      Additional mutational analyses confirmed this hypothesis. Interestingly, none of
      these four tyrosines was individually critical for the interaction between Crk-II
      and IRS-4, but when all four tyrosines were simultaneously mutated to
      phenylalanine, the IGF-I induced interaction between these molecules was
      abolished. Taken together, these results suggest a novel mechanism of Crk-II
      binding to tyrosine phosphorylated proteins.

PMID- 11316749
TI  - 17beta-estradiol treatment decreases steroidogenic enzyme messenger ribonucleic
      acid levels in the rainbow trout testis.
AB  - In fish, estrogens are well known for their involvement in ovarian
      differentiation and have been shown to be very potent feminizing agents when
      administrated in vivo during early development. However, the mechanism of action
      of exogenous estrogens is poorly understood. We report here on the feminizing
      effects of estrogen treatment on the testicular levels of some steroidogenic
      enzyme messenger RNAs [mRNAs; cholesterol side-chain cleavage (P450scc), 17
      hydroxylase/lyase (P450c17), 3beta-hydroxysteroid dehydrogenase (3betaHSD),
      11beta-hydroxylase (P45011beta), and aromatase (P450aro)] in the rainbow trout,
      Oncorhynchus mykiss. Treatment was carried out by dietary administration of
      17beta-estradiol (E(2); dosage of 20 mg/kg diet) to a genetically all male
      population. Steroidogenesis in the differentiating testis was demonstrated to be
      strongly altered by E(2), as this treatment resulted in considerable decrease in
      P450c17, 3betaHSD, and P45011beta mRNAs after only 10 days of treatment. In
      contrast, P450scc and P450aro mRNA levels were unaffected by E(2), with P450scc
      mRNA levels remaining unaltered and P450aro not stimulated by this feminizing
      estrogen treatment. To better characterize this E(2) effect, the same treatment
      was applied on postdifferentiating males, and roughly the same expression pattern
      was detected with a considerable decrease in testicular P450c17, 3betaHSD, and
      P45011beta mRNAs and a significant, but reduced, decrease in P450scc mRNA. In the
      interrenal, these steroidogenic enzyme mRNAs were not significantly affected by
      this E(2) treatment, except for a slight, but significant, decrease in P450scc
      mRNA. These results clearly demonstrate that estrogens have profound effects on
      testicular steroidogenesis and that they are acting specifically on the testis by
      decreasing mRNA steady state levels of many steroidogenic enzyme genes. The
      decrease in P45011beta mRNA, and thus inhibition of the synthesis of testicular
      11-oxygenated androgens, may be an important step required for the active
      feminization of these genetic males.

PMID- 11316750
TI  - A potential role for adrenomedullin as a local regulator of bone growth.
AB  - Bone remodeling is a complex process of coordinated resorption and formation of
      bone, which is regulated by systemic hormones and by local factors. We have
      previously shown that the peptide hormone adrenomedullin is mitogenic to
      osteoblastic cells in vitro and that it promotes bone growth in vivo. The aim of
      the present study was to characterize the expression of molecules that may
      mediate adrenomedullin signaling in osteoblasts and to investigate the expression
      of adrenomedullin itself in these cells. The first adrenomedullin receptor that
      was cloned is the seven-transmembrane G protein-coupled receptor, L1. Two
      additional receptors for adrenomedullin, which arise from interactions between
      calcitonin receptor-like receptor and receptor activity modifying proteins 2 or
      3, have now been described. In the current study, we used RT-PCR and Northern
      blot analysis to demonstrate that messenger RNA for the three adrenomedullin
      receptors, as well as for adrenomedullin itself, is expressed in primary rat
      osteoblasts. Treating primary osteoblasts with transforming growth factor-beta
      and insulin-like growth factor-I moderately reduced adrenomedullin RNA levels,
      whereas PTH had no effect. We have shown by immunocytochemistry that
      adrenomedullin peptide is present in osteoblasts, and by competitive binding
      assays that (125)I-adrenomedullin binds with high affinity to intact osteoblasts
      and to osteoblast cell membranes. Coexpression of adrenomedullin and
      adrenomedullin receptors in osteoblasts, taken together with our previous finding
      that adrenomedullin is mitogenic to these cells, raises the possibility that this
      peptide is a local regulator of bone growth.

PMID- 11316751
TI  - Cycles of transcription and translation do not comprise the gonadotropin
      releasing hormone pulse generator in GT1 cells.
AB  - Neural control of reproduction is achieved through episodic GnRH secretion, but
      little is known about the molecular mechanisms underlying pulse generation. The
      ultradian time domain of GnRH release suggests mechanisms ranging from
      macromolecular synthesis to posttranslational modification could be involved. We
      tested if messenger RNA (mRNA) or protein synthesis are components of the pulse
      generator by determining the effects of transcription and translation inhibitors
      on episodic GnRH release from immortalized GT1-1 GnRH neurons. Time course and
      efficacy of transcription and translation blockade were assessed by determining
      the ability of specific inhibitors to block the robust, rapid induction of c-fos
      mRNA or protein accumulation by forskolin (10 microM). The transcription
      inhibitors actinomycin D (ACT-D, 20 microM) or 5,6-dichlorobenzimidazole riboside
      (DRB, 100 microM), or the translation inhibitors anisomycin (ANI, 10 microM) or
      puromycin (PUR, 10 microM) were applied to GT1-1 cells 30, 15, or 0 min before
      forskolin. Northern and Western blots revealed blockade of transcription and
      translation was rapid and essentially complete. GT1-1 cells were perifused for a
      90- to 120-min control period then for 100-130 min with vehicle or inhibitor to
      examine pulsatile GnRH secretion. GnRH interpeak intervals, peak amplitude, and
      peak area were not different between control and experimental periods of cells
      treated with vehicle (n = 15), ACT-D (n = 10), DRB (n = 6), ANI (n = 8), and PUR
      (n = 6; P > 0.05). This study presents the first clear evidence that the series
      of reactions resulting in secretion of a GnRH pulse do not include cycles of
      transcription and translation. Although these mechanisms would be required to
      replenish components of the pulse generator, they are not integral components of
      this oscillator. We hypothesize that posttranslational events underlie episodic
      GnRH release in GT1-1 cells.

PMID- 11316752
TI  - Transforming growth factor-beta3 perturbs the inter-Sertoli tight junction
      permeability barrier in vitro possibly mediated via its effects on occludin,
      zonula occludens-1, and claudin-11.
AB  - Throughout spermatogenesis, inter-Sertoli tight junctions (TJs) that create the
      blood-testis barrier in the rat must be disassembled and reassembled to permit
      the timely passage of preleptotene spermatocytes from the basal to the adluminal
      compartment of the seminiferous epithelium. However, the mechanism(s) and the
      participating molecules that regulate this event are largely unknown. Although
      there is no in vitro model to study the event and regulation of inter-Sertoli TJ
      disassembly, primary cultures of Sertoli cells in vitro can be used to study
      junction assembly. In this study, we sought to investigate whether cytokines are
      involved in the inter-Sertoli TJ assembly in vitro. Sertoli cells isolated from
      20-day-old rats were cultured at a density of 0.5-1.2 x 10(6) cells/cm(2) on
      Matrigel-coated dishes or bicameral units for 8-9 days. The steady-state
      messenger RNA levels of basic fibroblast growth factor (bFGF), transforming
      growth factor (TGF)-beta2, and TGF-beta3 at different time points were assessed
      by semiquantitative RT-PCR. In selected experiments, the assembly of inter
      Sertoli TJs was monitored by transepithelial electrical resistance measurement.
      It was found that there was no change in the expression of basic fibroblast
      growth factor throughout the entire culture period. However, there was a 2-fold
      reduction in the expression of TGF-beta2 and TGF-beta3 at the time inter-Sertoli
      TJs were being assembled. On days 5-8, after the inter-Sertoli TJs had been
      assembled, the Sertoli cell steady-state messenger RNA levels of TGF-beta2 and
      TGF-beta3 increased by as much as 3- and 6-fold, respectively, when compared with
      Sertoli cells on days 1-3 when TJs were being assembled. Also, it was found that
      recombinant TGF-beta3 added to Sertoli cells cultured in vitro at 1.2 x 10(6)
      cells/cm(2) on Matrigel-coated bicameral units perturbed the inter-Sertoli TJ
      permeability barrier dose-dependently. Moreover, the presence of TGF-beta3 also
      inhibited the transient and/or basal expression of several TJ-associated
      proteins, which include occludin, zonula occludens-1, and claudin-11 when inter
      Sertoli TJs were being assembled in vitro. These results suggest that TGF-beta
      plays a crucial role in regulating the complicated biochemical events of junction
      assembly in the testis.

PMID- 11316753
TI  - Is cadmium chloride-induced inter-sertoli tight junction permeability barrier
      disruption a suitable in vitro model to study the events of junction disassembly
      during spermatogenesis in the rat testis?
AB  - The events of germ cell movement during spermatogenesis are composed of
      intermittent phases of junction disassembly and reassembly. Although primary
      Sertoli cells cultured in vitro can be used to study junction reassembly, an in
      vitro model to study the events of junction disassembly is still lacking. We have
      assessed whether the CdCl(2)-induced inter-Sertoli tight junction (TJ)
      permeability barrier disruption in vitro can fill this gap. When Sertoli cells
      (1.2 x 10(6) cells/cm(2)) were cultured on Matrigel-coated bicameral units to
      allow the assembly of inter-Sertoli TJs, it was manifested by a steady rise in
      transepithelial electrical resistance across the Sertoli cell epithelia. Exposure
      of these cells on day 1 (i.e. 24 h after their isolation) to CdCl(2) at 5-10
      microM for 8 h could perturb the inter-Sertoli TJ assembly dose dependently
      without any apparent cytotoxicity. Likewise, when cells were exposed to CdCl(2)
      (0.1-5 microM) on day 4 for 8 h after inter-Sertoli TJs were already assembled,
      CdCl(2) also perturbed the maintenance of inter-Sertoli TJ permeability barrier
      dose dependently without signs of cell cytotoxicity. Although the perturbed inter
      Sertoli TJs were not capable of resealing even after the removal of CdCl(2), the
      presence of testosterone (T) at 1 x 10(-9) M allowed resealing of the inter
      Sertoli TJ barrier after CdCl(2) was removed, whereas the presence of 2 x 10(-7)
      M testosterone even protected Sertoli cells from CdCl(2)-induced damage. More
      important, the reassembly of inter-Sertoli TJs after CdCl(2)-induced TJ
      disruption was accompanied by changes in cellular gene expression of occludin and
      urokinase plasminogen activator, which mimicked their patterns during inter-
      Sertoli TJ assembly in vitro without CdCl(2) treatment. Based on these results,
      it is apparent that CdCl(2)-induced inter-Sertoli TJ disassembly is a potential
      in vitro model to study the events of junction disassembly.

PMID- 11316754
TI  - Growth inhibition in giant growth hormone transgenic mice by overexpression of
      insulin-like growth factor-binding protein-2.
AB  - To clarify the role of insulin-like growth factor (IGF)-binding protein-2 (IGFBP
      2) in postnatal growth regulation, we crossed hemizygous CMV-IGFBP-2 transgenic
      mice with hemizygous PEPCK-bGH transgenic mice, which are characterized by serum
      GH levels in the range of 2 microgram/ml. Four genetic groups were obtained:
      animals carrying both transgenes (GB), the GH (G) or the IGFBP-2 transgene (B),
      and nontransgenic controls (C). Male offspring were analyzed for serum levels of
      IGF-I, for serum and tissue levels of IGFBP-2, and for body and organ growth.
      Serum IGF-I levels were 2- to 3-fold increased (P < 0.001) in the GH
      overexpressing groups, with no difference between G and GB mice. Serum IGFBP-2
      levels were 4- to 9-fold (P < 0.001) increased both in B and GB vs. C and G mice.
      Western immunoblot analysis did not reveal differences in tissue IGFBP-2 levels
      between B and GB mice. IGFBP-2 levels were highest in pancreas, followed by
      skeletal muscle, heart, kidney, brain, skin, and spleen. No elevation of IGFBP-2
      was found in the liver. Body weight gain of G and GB mice was significantly
      increased vs. C and B mice, resulting in almost 2-fold increased body weights at
      the age of 15 weeks. However, there was a significant reduction in body weight of
      GB vs. G mice (17%; P < 0.001) and of B vs. C mice (13%; P < 0.05). This was
      primarily caused by a marked reduction of carcass weight (GB vs. G, 27%; B vs. C,
      21%; P < 0.001). Measurements of nose-rump-length, organ (brain, heart, spleen,
      liver, pancreas, kidney), and tissue weights (skin, carcass, abdominal fat) in 5-
      and 15-week-old mice revealed several indications that the growth-inhibiting
      effect of IGFBP-2 overexpression was more marked in high-GH/IGF-I mice: 1) At 5
      weeks of age, GB mice displayed a significant reduction of all growth parameters
      except for the weight of abdominal fat, when compared with G mice, whereas only
      brain weight was significantly reduced in B vs. C mice. 2) In 15-week-old
      animals, a significant reduction in all growth parameters, except for spleen and
      abdominal fat weights, was seen in GB vs. G mice, whereas only nose-rump-length
      and the weights of carcass and brain were significantly reduced in B vs. C mice.
      Our study demonstrates, for the first time, the potential of IGFBP-2 to inhibit
      GH-stimulated growth in giant transgenic mice, providing further evidence for an
      inhibitory effect of this IGFBP in vivo.

PMID- 11316755
TI  - Concomitant increase of G protein-coupled receptor kinase activity and uncoupling
      of beta-adrenergic receptors in rat myometrium at parturition.
AB  - The myometrial beta-adrenergic receptor (beta-AR)-adenylyl cyclase pathway is
      markedly desensitized at the end of pregnancy in the rat. We have investigated
      whether changes in the amount and/or the activity of G protein-coupled receptor
      kinase (GRK) occurred at the same period of pregnancy. Using Northern and Western
      blotting, we have identified GRK2, GRK5, GRK6, and a small amount of GRK3 in late
      pregnant rat myometrium. GRK activity, as measured by in vitro phosphorylation of
      rhodopsin, was detected in both cytosolic and plasma membrane fractions.
      Interestingly, in the 6-10 h preceding parturition, there was a substantial
      increase (+190%) of myometrial membrane-associated GRK activity. This was
      associated with an increase in membrane GRK2 immunoreactivity. Such alterations
      occurred concomitantly with uncoupling of beta-AR, as assessed by quantification
      of high-affinity binding receptors. These data suggest that GRK activity increase
      may be one of the mechanisms underlying alterations in the coupling between beta
      AR and adenylyl cyclase and may thus contribute to the initiation of myometrial
      contractions at term.

PMID- 11316756
TI  - Overexpression of parathyroid hormone-related protein enhances apoptosis in the
      rat intestinal cell line, IEC-6.
AB  - We used the rat intestinal cell line, IEC-6, to study potential effects of
      overexpression of PTH-related protein (PTHrP) on apoptosis. A clonal line of
      PTHrP-overexpressing cells was established by stably transfecting parental cells
      with PTHrP complementary DNA in a sense orientation (sense). A similarly
      transfected line stably, transfected with empty vector, served as control
      (vector). Immunoreactive PTHrP, measured in culture medium, showed that sense
      cells secreted approximately 30 times as much PTHrP as did vector control cells.
      Apoptosis induced by serum withdrawal was evaluated by several methods. DNA
      laddering was demonstrable in sense-transfected cells as early as 12 h after
      serum withdrawal but not until later time points in vector-transfected control
      cells. Flow cytometric analysis of propidium iodide-stained cells showed a
      greater increase in the sub-G1 (apoptotic) population in sense cells, compared
      with vector. Fluorescent microscopy with Hoechst 33258 dye showed increased
      nuclear fragmentation and condensation in sense cells. Studies of apoptotic gene
      expression by ribonuclease protection assay, and protein by Western blot
      analysis, showed an enhanced ratio of Bax to Bcl-x(L) in sense cells. Mutation of
      the PTHrP nuclear localization amino acid sequence negated the ability of PTHrP
      to enhance apoptosis.

PMID- 11316757
TI  - Endotoxin inhibits pituitary responsiveness to gonadotropin-releasing hormone.
AB  - Immune/inflammatory challenges powerfully suppress reproductive neuroendocrine
      activity. This inhibition is generally considered to be centrally mediated via
      mechanisms that regulate GnRH secretion. The present study provides two lines of
      evidence that bacterial endotoxin, a commonly used model of immune/inflammatory
      challenge, also acts to inhibit pituitary responsiveness to GNRH: In the first
      experiment, pulsatile secretion of GnRH into pituitary portal blood and LH into
      peripheral blood were monitored in ovariectomized ewes treated with a low dose of
      endotoxin. Although this treatment only marginally suppressed GnRH pulsatile
      secretion, it markedly disrupted LH pulsatility. In extreme cases, the low dose
      of endotoxin blocked LH pulses without inhibiting endogenous GnRH pulses, thereby
      uncoupling GnRH and LH pulsatile suppression. In the second experiment, we tested
      the hypothesis that endotoxin inhibits pituitary responsiveness to exogenous GnRH
      pulses. Hourly pulses of GnRH were delivered to ovariectomized ewes in which
      endogenous GnRH secretion was blocked. Endotoxin suppressed the amplitude of GnRH
      induced LH pulses. Together, these observations support the conclusion that
      endotoxin inhibits pituitary responsiveness to GNRH:

PMID- 11316758
TI  - Organization and evolution of the human growth hormone receptor gene 5'-flanking
      region.
AB  - Previous studies have identified eight variant human GH receptor (hGHR) messenger
      RNA (mRNAs; V1-V8), that differ in their 5'-untranslated regions (5'UTRs) but
      splice into the same site just upstream of the translation start site in exon 2;
      thus, they encode the same protein. Here we report a novel variant, V9, and
      describe the mapping of all nine 5'UTR sequences within 40 kb upstream of exon 2.
      A cluster of three sequences, V2-V9-V3 (termed module A), lies furthest 5', and
      approximately 16 kb downstream is a second cluster of four exons, V7-V1-V4-V8
      (module B). V6 is midway between modules A and B. Module B is about 18 kb
      upstream of V5, which lies adjacent to exon 2. hGHR expression is under
      developmental- and tissue-specific regulation, and expression of the variant
      mRNAs is related to their position within the 5'-flanking region; whereas module
      A (V2,V9,V3) and V5 variants are widely expressed, module B (V7,V1,V4,V8) and V6
      variant mRNAs are detectable only in postnatal liver. Transcriptional start sites
      for V1 and V9 (representing the two different modules) were identified, showing
      that postnatal liver-specific expression of V1 is driven from two TATA boxes,
      whereas the ubiquitous V9 transcript has a single start site and a TATA-less
      promoter. V9 promoter activity was shown by in vivo and in vitro transfection
      assays, and an NF-Y binding site was demonstrated by electromobility shift assay.
      Thus, the regulatory regions of the hGHR gene are complex, and the clustering of
      seven 5'UTR exons within two modules with distinctly different mRNA expression
      patterns is the most striking feature.

PMID- 11316759
TI  - Expression of the human beta(3)-adrenergic receptor gene in SK-N-MC cells is
      under the control of a distal enhancer.
AB  - Mechanisms of transcriptional regulation of the human beta(3)-adrenergic receptor
      were studied using SK-N-MC cells, a human neuroblastoma cell line that expresses
      beta(3)- and beta(1)-adrenergic receptors endogenously. Deletions spanning
      different portions of a 7-kb 5'-flanking region of the human beta(3)-adrenergic
      receptor gene were linked to a luciferase reporter and transfected in SK-N-MC, CV
      1, and HeLa cells. Maximal luciferase activity was observed when a 200-bp region
      located between -6.5 and -6.3 kb from the translation start site was present.
      This region functioned only in SK-N-MC cells. Electrophoretic mobility shift
      assays of nuclear extracts from SK-N-MC, CV-1, and HeLa cells using double
      stranded oligonucleotides spanning different portions of the 200-bp region as
      probes and transient transfection studies revealed the existence of three cis
      acting regulatory elements: A) -6.468 kb-AGGTGGACT--6.458 kb, B) -6.448 kb
      GCCTCTCTGGGGAGCAGCTTCTCC-6.428 kb, and C) -6.405 kb-20 repeats of CCTT-6.385 kb.
      These elements act together to achieve full transcriptional activity. Mutational
      analysis, antibody supershift, and electrophoretic mobility shift assay
      competition experiments indicated that element A binds the transcription factor
      Sp1, element B binds protein(s) present only in nuclear extracts from SK-N-MC
      cells and brown adipose tissue, and element C binds protein(s) present in both SK
      N-MC and HeLa cells. In addition, element C exhibits characteristics of an S1
      nuclease-hypersensitive site. These data indicate that cell-specific positive cis
      regulatory elements located 6.5 kb upstream from the translation start site may
      play an important role in transcriptional regulation of the human beta(3)
      adrenergic receptor. These data also suggest that brown adipose tissue-specific
      transcription factor(s) may be involved in the tissue-specific expression of the
      beta(3)-adrenergic receptor gene.

PMID- 11316760
TI  - Physiological control of Xunc18 expression in neuroendocrine melanotrope cells of
      Xenopus laevis.
AB  - In mammals, the brain-specific protein munc18-1 regulates synaptic vesicle
      exocytosis at the synaptic junction, in a step before vesicle fusion. We
      hypothesize that the rate of biosynthesis of munc18-1 messenger RNA (mRNA) and
      the amount of munc18-1 present in neurons and neuroendocrine cells are related to
      the physiologically controlled state of activity. To test this hypothesis, the
      homolog of munc18-1 in the clawed toad Xenopus laevis, xunc18, was studied in the
      brain and in the neuroendocrine melanotrope cells in the intermediate lobe of the
      pituitary gland, at both the mRNA and the protein level. In toads adapted to a
      black background, the melanotropes release the peptide alpha-melanophore
      stimulating hormone (alpha-MSH), which induces darkening of the skin, whereas in
      animals adapted to a white background the cells hardly release but store alpha
      MSH, making the animal's skin look pale. The intermediate pituitary lobe of black
      adapted animals revealed a strong hybridization reaction with the xunc18 mRNA
      probe, whereas a much weaker hybridization was observed in the intermediate lobe
      of white-adapted animals (optical density black: 3.4 +/- 0.2 vs. white: 0.8 +/-
      0.1; P < 0.02). Immunocytochemically, Xenopus munc18-like protein has been
      detected throughout the brain, in identified neuronal perikarya as well as in
      axon tracts. Western blot analysis and immunocytochemistry further demonstrated
      the presence of xunc18 in the neural, intermediate and distal lobe of the
      pituitary gland. Xunc18 protein was furthermore determined in immunoblots of
      homogenates of melanotropes dissociated from the pituitary gland. In melanotropes
      of toads adapted to a black background, the integrated optical density of the
      xunc18 immunosignal was 2.7 +/- 0.5 times higher than in cells of white-adapted
      toads (P < 0.0001). It is concluded that, in Xenopus melanotrope cells, the
      amounts of both xunc18 mRNA and xunc18 protein are up-regulated in conjunction
      with the induction of exocytosis of alpha-MSH as a result of a physiological
      stimulation (environmental light condition). We propose that xunc18 is involved
      in physiologically controlled exocytotic secretion of neuroendocrine messengers.

PMID- 11316761
TI  - Phenotypic manifestations of insulin-like growth factor-binding protein-3
      overexpression in transgenic mice.
AB  - In cell culture systems insulin-like growth factor (IGF)-binding protein-3 (IGFBP
      3) can both enhance and inhibit IGF-I action. To investigate the biological role
      of IGFBP-3 in vivo, transgenic (Tg) mice that constitutively overexpress the
      human IGFBP-3 complementary DNA (cDNA) driven by the mouse phosphoglycerate
      kinase I (PGK) and the cytomegalovirus (CMV) promoters were examined. Serum
      levels of human IGFBP-3 in CMVBP-3 and PGKBP-3 Tg mice were 4.7 and 5.8
      microgram/ml, respectively and total IGFBP-3 was increased 4.9- and 7.7-fold
      compared with that in wild-type (Wt) mice. In PGKBP-3 Tg mice the levels of
      transgene expression were similar in all tissues. Although CMVBP-3 mice
      demonstrated similar levels of expression of the transgene as PGKBP-3 mice in
      most tissues, markedly elevated expression was apparent in the kidney and heart.
      The transgene-derived IGFBP-3 circulated as a 150-kDa ternary complex, and serum
      IGF-I levels were elevated 1.9- to 2.8-fold in Tg mice compared with Wt mice. A
      significant reduction in birth weight of approximately 10% and a modest reduction
      in litter size were apparent in both Tg strains. Early postnatal growth, as
      assessed by both body weight and length, was significantly reduced in Tg mice
      compared with Wt mice. This was more marked in PGKBP-3 than in CMVBP-3 mice, who
      demonstrated a propensity to adiposity after weaning. The relative organ weights
      of brain and kidney were reduced in both Tg strains, whereas liver size and
      epididymal fat were significantly increased in CMVBP-3, but not PGKBP-3, mice.
      Our data indicate that overexpression of IGFBP-3 is associated with modest
      intrauterine and postnatal growth retardation despite elevated circulating IGF-I
      levels.

PMID- 11316762
TI  - Receptor-operated osteoclast calcium sensing.
AB  - Osteoclasts "sense" elevated extracellular calcium, which leads to cytoskeletal
      changes that may be linked to phospholipase C (PLC) activation and the associated
      rise in intracellular calcium ([Ca(2+)](i)). Since PLC is linked to transient
      receptor potential channels (trp), we hypothesized that receptor activated
      calcium influx due to this channel type would be activated by osteoclasts sensing
      [Ca(2+)](e). We found that high [Ca(2+)](e) induced similar intracellular Ca(2+)
      rises in chicken osteoclasts with or without intracellular Ca(2+) store depletion
      by either TPEN or thapsigargin, thus defining store-insensitive Ca(2+) influx.
      This store-insensitive calcium sensing component was blocked by the PLC
      antagonist U73122. Also, the calcium channel inhibitor SKF 96365, a blocker of
      store-independent trp-like channels, was effective in inhibiting calcium sensing
      in the presence of thapsigargin. Thus, a store-independent component of calcium
      sensing was associated with ion channels linked to PLC. Since receptor activated
      transient receptor potential (trp) family cation channels open in a PLC-dependent
      and store-independent manner, we suggest that receptor operated channels are
      activated in osteoclasts stimulated by high extracellular Ca(2+).

PMID- 11316763
TI  - Parathyroid hormone stimulates fra-2 expression in osteoblastic cells in vitro
      and in vivo.
AB  - PTH and PTH-related protein (PTHrP) are key mediators of skeletal development and
      homeostasis through their activation of the PTH-1 receptor. Previous studies have
      found that several AP-1 family members are regulated by PTH, such as c-fos, fra
      1, and c-jun. There are numerous genes in the bone microenvironment that contain
      AP-1 sites, and different Fos family members are reported to have opposing
      transcriptional activities at AP-1 sites. The purpose of this study was to
      identify the effects of PTH on expression of the AP-1 protein complex member, fra
      2, to extend our understanding of transcriptional regulators of PTH action. PTH
      induction of fra-2 messenger RNA (mRNA) levels in MC3T3-E1 preosteoblastic cells
      was maximal with 0.1 microM PTH (1-34). The expression in vitro was greatest 1 h
      after treatment and was present with N-terminal PTH but not PTH (7-34) or (53
      84). Cycloheximide treatment induced fra-2 expression, and actinomycin D
      inhibited basal and PTHrP-induced expression. AP-1 protein in nuclear extracts of
      MC3T3-E1 cells was increased with PTH treatment at 3 h and consisted of high
      levels of Fra-2 protein, as evidenced by a supershift in an electrophoretic
      mobility shift assay and Western blot analysis. Up-regulation of steady-state fra
      2 mRNA was also noted in vivo, where injection of PTH (1-34) (20 microgram)
      resulted in a more-than-7-fold maximal increase in fra-2 mRNA expression in the
      calvaria of mice, after 1 h of treatment. These data add to the transcriptional
      mediators induced by PTH and suggest that the interplay of AP-1 family members
      will provide insight into regulatory pathways of PTH and PTHrP for their anabolic
      and catabolic actions in bone.

PMID- 11316764
TI  - Regulation of expression of 11beta-hydroxysteroid dehydrogenase type 1 in adipose
      tissue: tissue-specific induction by cytokines.
AB  - Patients with glucocorticoid excess develop central obesity, yet in simple
      obesity, circulating glucocorticoid levels are normal. We have suggested that the
      increased activity and expression of the enzyme 11beta-hydroxysteroid
      dehydrogenase type 1 (11betaHSD1) generating active cortisol from cortisone
      within adipose tissue may be crucial in the pathogenesis of obesity. In this
      study primary cultures of human hepatocytes and adipose stromal cells (ASC) were
      used as in vitro models to investigate the tissue-specific regulation of
      11betaHSD1 expression and activity. Treatment with tumor necrosis factor-alpha
      (TNFalpha) caused a dose-dependent increase in 11betaHSD1 activity in primary
      cultures of both sc [1743.1 +/- 1015.4% (TNFalpha, 10 ng/ml); P < 0.05 vs.
      control (100%)] and omental [375.8 +/- 57.0% (TNFalpha, 10 ng/ml); P < 0.01 vs.
      control (100%)] ASC, but had no effect on activity in human hepatocytes [90.2 +/-
      2.8% (TNFalpha, 10 ng/ml); P = NS vs. control (100%)]. Insulin-like growth factor
      I (IGF-I) caused a dose-dependent inhibition of 11betaHSD1 activity in sc [49.7
      +/- 15.0% (IGF-I, 100 ng/ml]; P < 0.05 vs. control (100%)] and omental [71.6 +/-
      7.5 (IGF-I, 100 ng/ml); P < 0.01 vs. control (100%)] stromal cells, but not in
      human hepatocytes [101.8 +/- 15.7% (IGF-I, 100 ng/ml); P = NS vs. control
      (100%)]. Leptin treatment did not alter 11betaHSD1 activity in human hepatocytes,
      but increased activity in omental ASC [135.8 +/- 14.1% (leptin, 100 ng/ml); P =
      0.08 vs. control (100%)]. Treatment with interleukin-1beta induced 11betaHSD1
      activity and expression in sc and omental ASC in a time- and dose-dependent
      manner. 15-Deoxy-12,14-PGJ2, the putative endogenous ligand of the orphan nuclear
      receptor peroxisome proliferator-gamma, significantly increased 11betaHSD1
      activity in omental cells [179.7 +/- 29.6% (1 microM); P < 0.05 vs. control
      (100%)] and sc [185.3 +/- 12.6% (1 microM); P < 0.01 vs. control (100%)] ASC, and
      it is possible that expression of this ligand may ensure continued cortisol
      generation to permit adipocyte differentiation. Protease inhibitors used in the
      treatment of human immunodeficiency virus infection are known to cause a
      lipodystrophic syndrome and central obesity, but saquinavir, indinavir, and
      neflinavir caused a dose-dependent inhibition of 11betaHSD1 activity in primary
      cultures of human omental ASC. 11betaHSD1 expression is increased in human
      adipose tissue by TNFalpha, interleukin-1beta, leptin, and orphan nuclear
      receptor peroxisome proliferator-gamma agonists, but is inhibited by IGF-I. This
      autocrine and/or paracrine regulation is tissue specific and explains recent
      clinical data and animal studies evaluating cortisol metabolism in obesity.
      Tissue-specific 11betaHSD1 regulation offers the potential for selective enzyme
      inhibition within adipose tissue as a novel therapy for visceral obesity.

PMID- 11316765
TI  - Inhibition of growth and increased expression of insulin-like growth factor
      binding protein-3 (IGFBP-3) and -6 in prostate cancer cells stably transfected
      with antisense IGFBP-4 complementary deoxyribonucleic acid.
AB  - Insulin-like growth factor-binding proteins (IGFBPs) both stimulate and inhibit
      IGF activity, and in the M12 prostate cancer cell line, overexpression of IGFBP-4
      was shown to delay tumorigenesis while decreasing the production of IGFBP-2. We
      have performed the reverse experiment, inhibition of IGFBP-4 expression with
      antisense complementary DNA, in two prostate tumor cell lines, ALVA-31 and M12.
      Expression of antisense messenger RNA transcripts was verified by RNase
      protection assays, and inhibition of mature IGFBP-4 in cell medium was
      demonstrated by Western blotting. Both transfected lines (ALVA-31asBP4 and
      M12asBP4) proliferated more slowly in monolayer culture than parental controls.
      Colony formation in soft agar was strongly inhibited in both cases, and the rate
      of tumor formation and growth in male athymic nude mice injected with M12asBP4
      was markedly reduced relative to that in mice receiving M12 control cells.
      Apoptosis induced by the topoisomerase inhibitor etoposide was also enhanced in
      transfected cells. The effects on colony formation in soft agar and tumor
      formation in mice were maintained for the duration of the experiments, in
      contrast to the delayed growth observed in the previous study of IGFBP-4
      overexpression. A significant difference was found in the patterns of IGFBP
      expression; production of both messenger RNA and protein for IGFBP-3 and IGFBP-6
      was greatly increased in the M12asBP4 and ALVA31asBP4 cell lines. Up-regulation
      of these binding proteins has been observed in association with actions of 1,25
      dihydroxyvitamin D(3) in prostate cancer cells, and the data suggest a role for
      IGFBP-3 and IGFBP-6 in the suppression of prostate tumor cell growth.

PMID- 11316766
TI  - The MEF2A and MEF2D isoforms are differentially regulated in muscle and adipose
      tissue during states of insulin deficiency.
AB  - Previously we have demonstrated that striated muscle GLUT4 gene expression
      decreased following streptozotocin-induced diabetes due to a loss of MEF2A
      transcription factor expression without any significant effect on the MEF2D
      isoform (Mora, S. and J. E. Pessin (2000) J Biol Chem, 275:16323-16328). In
      contrast to both cardiac and skeletal muscle, adipose tissue displays a selective
      decrease in MEF2D expression in diabetes without any significant alteration in
      MEF2A protein content. Adipose tissue also expresses very low levels of the MEF2
      transcription factors and nuclear extracts from white adipose tissue exhibit poor
      in vitro binding to the MEF2 element. However, addition of in vitro synthesized
      MEF2A to adipose nuclear extracts results in the formation of the expected
      MEF2/DNA complex. More importantly, binding to the MEF2 element was also
      compromised in the diabetic condition. Furthermore, in vivo overexpression of
      MEF2A selectively in adipose tissue did not affect GLUT4 or MEF2D expression and
      was not sufficient to prevent GLUT4 down-regulation that occurred in insulin
      deficient states.

PMID- 11316768
TI  - Identification of an SAS (Sp1c adjacent site)-like element in the distal 5'
      flanking region of the rat lutropin receptor gene essential for cyclic adenosine
      3',5'-monophosphate responsiveness.
AB  - One of the hallmarks of the differentiation of granulosa cells is the estradiol
      and FSH/cAMP-dependent induction of the LH receptor (LHR). Previous studies using
      granulosa cells isolated from diethylstilbestrol-pretreated immature rats
      identified a novel cAMP-responsive element termed the SAS site (Sp1c adjacent
      site) in the promoter region of the rat (r) LHR gene. The studies presented
      herein show that there is an additional distal site located at nucleotide (nt) 
      933/-924 that appears to interact with the same transcription factor that binds
      to the promoter SAS site. Similar to the SAS site, the complex formed between
      granulosa cell nuclear extracts and this distal site is enhanced by cAMP
      treatment of the granulosa cells. The core sequence required for the formation of
      the DNA/protein complex at this distal rLHR site was determined to be
      AGTGG(A)GGGG. With the exception of adenine at -928, substitution of any residue
      within this sequence prevented formation of this complex. The core sequence of
      this distal site differs from that of the proximal SAS site, which is GGGGG, and
      hence the distal site has been termed a SAS-like site. Reporter gene assays using
      constructs containing the -2,109/-1 region of the rLHR demonstrate that mutation
      of the distal SAS-like site abolishes the cAMP-induced transcription of the rLHR
      gene in rat granulosa cells, underscoring the functional significance of this
      site. Given the lack of sequences in the 5'-flanking region of the rLHR gene
      consistent with known cAMP-responsive elements, the identification of the novel
      SAS and SAS-like sites in the rLHR gene provides important clues toward
      understanding the mechanisms by which the rLHR gene is induced by FSH/cAMP.

PMID- 11316767
TI  - Identification of thyroid hormone transporters in humans: different molecules are
      involved in a tissue-specific manner.
AB  - We have recently identified that rat organic anion transporters, polypeptide2
      (oatp2) and oatp3, both of which transport thyroid hormones. However, in humans
      the molecular organization of the organic anion transporters has diverged, and
      the responsible molecule for thyroid hormone transport has not been clarified,
      except for human liver-specific transporter (LST-1) identified by us. In this
      study we isolated and characterized a novel human organic anion transporter, OATP
      E from human brain. The isolated complementary DNA encodes a polypeptide of 722
      amino acids with 12 transmembrane domains. A rat counterpart, oatp-E, was also
      identified. Homology analysis and the phylogenetic tree analysis revealed that
      OATP-E/oatp-E is a subfamily of the organic anion transporter. Human OATP-E
      transported 3,3',5-triiodo-L-thyronine (K(m), 0.9 microM), thyronine, and rT(3)
      in a Na(+)-independent manner. Although the clone was isolated from the brain,
      OATP-E messenger RNA was abundantly expressed in various peripheral tissues. The
      rat counterpart, oatp-E, also transported 3,3',5-triiodo-L-thyronine. In
      addition, in this study we revealed that human OATP, which is exclusively
      expressed in the brain, transported 3,3',5-triiodo-L-thyronine (K(m), 6.5
      microM), T(4) (K(m), 8.0 microM), and rT(3). These data suggest that in humans,
      several different molecules are involved in transporting thyroid hormone: OATP in
      the brain, LST-1 in the liver, and OATP-E in peripheral tissues.

PMID- 11316769
TI  - Opioids suppress basal and nicotine-induced catecholamine secretion via a
      stabilizing effect on actin filaments.
AB  - Catecholamine secretion and actin filament disassembly are closely coupled in
      chromaffin cells. Opioid suppression of catecholamine secretion is fast and
      transient, both characteristics of actin filament involvement. The aim of the
      present work was to test the hypothesis that opioids suppress catecholamine
      secretion via an inhibitory effect on actin filament disassembly. For this
      purpose we used the PC12 rat pheochromocytoma cell line. Norepinephrine and
      dopamine were measured by enzyme-linked immunosorbent assay or RIA. Polymerized
      actin was measured by rhodamine-phalloidin and visualized by confocal laser
      scanning microscopy. Opioids suppressed basal catecholamine secretion. The onset
      of this effect was fast and transient, peaking at 2 min, and was reversible by
      opioid antagonists. Synchronously, opioids suppressed actin filament disassembly;
      this was also reversible by opioid antagonists. Cytochalasin B prevented the
      inhibitory effect of opioids on catecholamine secretion. In addition, opioids
      suppressed the stimulatory effect of nicotine on catecholamine secretion and
      actin depolymerization. Changes in actin cytoskeleton in neuron-like PC12 cells
      make them resistant to both effects of opioids, i.e. on catecholamine secretion
      and actin disassembly. In conclusion, our data suggest that the suppressive
      effect of opioids on basal and nicotine-induced catecholamine secretion may
      result from an opioid-provoked stabilization of cortical actin. It also appears
      that basal catecholamine secretion is associated with opioid-sensitive machinery
      regulating the continuous formation of short-lived areas of cortical actin
      filament disassembly.

PMID- 11316770
TI  - Prolactin-releasing peptide as a novel stress mediator in the central nervous
      system.
AB  - A1/A2 noradrenergic neurons in the medulla oblongata are well known to mediate
      stress signals in the central nervous system. Stress activates A1/A2
      noradrenergic neurons, and then noradrenaline (NA) stimulates ACTH secretion
      through hypothalamic CRH. On the other hand, PRL-releasing peptide (PrRP) was
      recently isolated and was found to be produced by some A1/A2 neurons and the
      dorsomedial hypothalamic nucleus. We previously demonstrated that PrRP neurons
      make synapse-like contact with hypothalamic CRH neurons. In fact, we demonstrated
      that the central administration of PrRP stimulates CRH-mediated ACTH secretion.
      Furthermore, it has been reported that PrRP neurons in A1/A2 cell groups are
      colocalized with tyrosine hydroxylase (TH), which is known as the marker enzyme
      of catecholaminergic neurons. These data strongly suggest that PrRP is related to
      stress-responsive signal transduction, and PrRP and NA cooperatively modulate the
      hypothalamo-pituitary-adrenal axis. We therefore examined the effect of water
      immersion-restraint stress on c-Fos protein accumulation in PrRP- and TH
      immunoreactive neurons. The synergistic effects of PrRP and NA on plasma ACTH
      elevation were also examined. The results clearly showed that c-Fos protein
      accumulation dramatically increased in the nuclei of A1/A2 and dorsomedial
      hypothalamic nucleus PrRP neurons. In addition, it was revealed that c-Fos
      protein was specifically expressed in the PrRP/TH double positive cells in the
      A1/A2 cell groups. We also demonstrated that the central administration of PrRP
      and NA in combination at subactive (noneffective) doses clearly induced plasma
      ACTH elevation. Here we report that PrRP is a novel and important mediator of the
      hypothalamo-pituitary-adrenal axis for the stress response.

PMID- 11316771
TI  - A splice variant of estrogen receptor beta missing exon 3 displays altered
      subnuclear localization and capacity for transcriptional activation.
AB  - There are two separate estrogen receptors (ERs), ERalpha and ERbeta. The ERbeta
      gene is variably spliced, and in some cases variant expression is high. Besides
      the full-length ERbeta (equivalent to ERbeta1), splice variants can encode
      proteins bearing an insert within the ligand-binding domain (beta2), a deletion
      of exon 3 (ERbeta1delta3) disrupting the DNA-binding domain, or both
      (ERbeta2delta3). Here we examine the intracellular localization and
      transcriptional properties of each of the ERbeta splice variants heterologously
      expressed in cultured cells. In accordance with ERalpha, ERbeta1 and ERbeta2 are
      both distributed in a reticular pattern within the nucleus after exposure to
      ligand. In contrast, ERbeta1delta3 and ERbeta2delta3 localize to discrete spots
      within the nucleus in the presence of ER agonists. In the presence of ER
      antagonists, the delta3 variants are distributed diffusely within the nucleus. We
      also show that the spots are stable nuclear structures to which the delta3
      variants localize in a ligand-dependent manner. Coactivator proteins of ER
      colocalize with delta3 variants in the spots in the presence of agonists. The
      delta3 variants of ERbeta can activate luciferase reporter constructs containing
      an activator protein complex-1 site, but not an estrogen response element (ERE).
      These data suggest that without an intact DNA-binding domain, ERbeta is
      functionally altered, allowing localization to discrete nuclear spots and
      activation from activator protein-1-containing reporter genes.

PMID- 11316772
TI  - Developmental regulation of vascular endothelial growth/permeability factor
      messenger ribonucleic acid levels in and vascularization of the villous placenta
      during baboon pregnancy.
AB  - Vascular endothelial growth/permeability factor (VEG/PF) has an important role in
      angiogenesis; however, very little is known about the developmental regulation of
      VEG/PF and the vascular system within the placenta during human pregnancy. In the
      present study, therefore, a developmental approach was used in the baboon to
      determine the placental source of VEG/PF and its fms-like tyrosine kinase (flt-1)
      and kinase-insert domain containing (KDR/flk-1) receptors, and whether the rise
      in estrogen with advancing pregnancy was associated with a corresponding increase
      in placental VEG/PF expression and vascularization. VEG/PF messenger RNA (mRNA)
      levels were determined by competitive RT-PCR in villous cell fractions isolated
      by Percoll gradient centrifugation from placentas obtained on days 45 and 54
      (very early), 60 (early), 100 (mid), and 165-170 (late) of baboon pregnancy (term
      = 184 days). Maternal peripheral serum estradiol increased from very low
      concentrations early in gestation (0.15-0.20 ng/ml) to an early surge of over 2.5
      ng/ml on days 60-85, and peak levels of 4-6 ng/ml late in baboon pregnancy.
      VEG/PF mRNA was expressed in low level in the syncytiotrophoblast (<2,000
      attomol/microgram total RNA), and values in this fraction did not change
      significantly with advancing gestation. VEG/PF mRNA expression was slightly
      greater in the inner villous core cell fraction; however, levels decreased (P <
      0.05) between early and late gestation. Cytotrophoblasts were a major source of
      VEG/PF mRNA and levels increased (P < 0.01) from 3,631 +/- 844 attomol/microgram
      total RNA on day 45 to 25,807 +/- 5,873 attomol/microgram total RNA on day 170.
      VEG/PF protein expression determined by immunocytochemistry was abundant in
      cytotrophoblasts and lower in the syncytiotrophoblast and inner villous core
      cells. The flt-1 and KDR/flk-1 receptors were expressed in the vascular
      endothelial cells of the baboon villous placenta. The percentage of villous
      placenta occupied by blood vessels and the number of vessels/mm(2) villous
      tissue, determined by image analysis, progressively increased (P < 0.001; r =
      0.97) from 3.4 +/- 0.2% and 447 +/- 29, respectively, on day 54 to 15.9 +/- 0.9%
      and 1,375 +/- 71, respectively, on day 170. In summary, the present study shows
      that villous cytotrophoblasts were a major source of VEG/PF mRNA and protein in
      the baboon villous placenta, and that cytotrophoblast VEG/PF mRNA levels and
      vascularization of the villous placenta closely paralleled the increase in
      estradiol concentrations of advancing pregnancy. These results are consistent
      with the concept that estrogen has an important role in establishing the new
      vascular system within the developing placenta during primate pregnancy and that
      VEG/PF mediates this process.

PMID- 11316773
TI  - Spatiotemporal messenger ribonucleic acid expression of ovarian tissue inhibitors
      of metalloproteinases throughout the rat estrous cycle.
AB  - The tissue inhibitors of metalloproteinases (TIMPs) within the ovary closely
      regulate the matrix metalloproteinases, enzymes capable of degrading components
      of the extracellular matrix. The purpose of this study was to examine the spatial
      and temporal messenger RNA (mRNA) expression of the TIMPs in the ovaries of
      normally cycling rats. Ovaries were collected at 1100 h on each day of the 4-day
      estrous cycle, and TIMP mRNA expression was examined by Northern blot, RT-PCR, or
      in situ hybridization. TIMP-1 mRNA levels were significantly higher on estrus
      than on any other day. Although the 1.0-kb TIMP-2 transcript did not change
      across the cycle, the 3.5-kb transcript decreased significantly between metestrus
      and diestrus. Expression of TIMP-3 mRNA decreased significantly between proestrus
      and estrus. TIMP-1, TIMP-2, and TIMP-3 mRNAs were primarily localized to the
      theca, stroma, and corpora lutea (CL) on all days of the cycle, but with distinct
      cyclic changes. Thecal expression of TIMP-1 and TIMP-2 mRNAs was especially high
      immediately before and after ovulation. TIMP-1 and TIMP-3 mRNAs, which were low
      to undetectable in the granulosa cells of preovulatory follicles, were greatly
      increased in the luteinizing cells of newly forming CL on estrus. Although the
      presence of TIMP-1 mRNA in the granulosa cells of preovulatory follicles by in
      situ hybridization was near background levels, it was specifically identified in
      granulosa cells of follicles on all days of the cycle using laser capture
      microdissection and RT-PCR. Both TIMP-2 and TIMP-3 transcripts were up-regulated
      in luteinized follicles on proestrus and were present throughout the cycle in
      regressing CL. In summary, the unique and dynamic expression patterns of the
      TIMPs suggest that they have important, yet distinct, functions in the ovary. The
      high levels of TIMP-1 mRNA in the CL on estrus indicate a likely role for this
      inhibitor in luteal formation. The presence of TIMP-2 mRNA in regressing CL
      suggests an involvement in luteal demise, whereas TIMP-3 may play a role in the
      health of the follicle as well as in CL regression.

PMID- 11316774
TI  - Tissue-specific targeting of the pthrp gene: the generation of mice with floxed
      alleles.
AB  - PTH-related peptide (PTHrP) has been implicated in a variety of developmental and
      homeostatic processes. Although mice homozygous for the targeted disruption of
      the Pthrp gene have greatly expanded our capacity to investigate the
      developmental roles of the protein, the perinatal lethality of these animals has
      severely hindered the analysis of Pthrp's postnatal physiological effects. To
      overcome this obstacle, we have generated mice homozygous for a floxed Pthrp
      allele, i.e. two loxP sites flanking exon 4 of the Pthrp gene, which encodes most
      of the protein, with the aim of accomplishing cell type- and tissue-specific
      deletion of the gene. The ability of the Cre enzyme to cause recombination
      between the loxP sites and excision of the intervening DNA sequence was tested in
      vivo by crossing this strain to mice carrying a cre transgene under the
      transcriptional control of the human beta-actin promoter. The ubiquitous deletion
      of the floxed allele in the cre/loxP progeny resulted in perinatal lethality as a
      consequence of aberrant endochondral bone formation, fully recapitulating all the
      phenotypic abnormalities observed in the conventional Pthrp knockout mouse. The
      availability of the floxed Pthrp mice will serve as a valuable tool in genetic
      experiments that aim to investigate the physiological actions of Pthrp in the
      postnatal state.

PMID- 11316775
TI  - Nerve growth factor is required for early follicular development in the mammalian
      ovary.
AB  - Nerve growth factor (NGF) epitomizes a family of proteins known as the
      neurotrophins (NTs), which are required for the survival and differentiation of
      neurons within both the central and peripheral nervous system. Synthesis of NGF
      in tissues innervated by the peripheral nervous system is consistent with its
      function as a target-derived trophic factor. However, the presence of low- and
      high-affinity NGF receptors in the gonads suggests another function for the NTs
      within the reproductive endocrine system. We now report that NGF is required for
      the growth of primordial ovarian follicles, a process known to occur
      independently of pituitary gonadotropins. Both the NT receptor p75(NTR) and the
      NGF tyrosine kinase receptor trkA were found to be expressed in the ovaries of
      infantile normal mice and mice carrying a null mutation of the NGF gene. The
      ovaries from homozygote NGF-null (-/-) mutant animals, analyzed after completion
      of ovarian histogenesis, exhibited a markedly reduced population of primary and
      secondary follicles in the presence of normal serum gonadotropin levels, and an
      increased number of oocytes that failed to be incorporated into a follicular
      structure. Assessment of mitogenic activity using two complementary proliferation
      markers revealed a conspicuous reduction in somatic cell proliferation in the
      ovaries of NGF-deficient mice. These results suggest that the delay in follicular
      growth observed in NGF(-/-) mice may be related to the loss of a proliferative
      signal provided by NGF to the nonneural endocrine component of the ovary.

PMID- 11316776
TI  - Effects of cartilage-derived morphogenetic proteins and osteogenic protein-1 on
      osteochondrogenic differentiation of periosteum-derived cells.
AB  - Localization studies and genetic evidence have implicated cartilage-derived
      morphogenetic proteins-1, -2 (CDMP-1 and CDMP-2), and osteogenic protein-1 (OP-1)
      in the osteochondrogenic differentiation of mesenchymal progenitor cells during
      embryonic development and in postnatal life. Based on their expression pattern
      and the evidence that periosteum contains mesenchymal cells in the cambium layer
      that can undergo bone and cartilage formation, we hypothesized that CDMPs and OP
      1 may be involved in long bone development and fracture healing. To test this
      hypothesis, periosteum-derived cells from young calves were cultured as
      monolayers under serum-free conditions with and without the addition of
      recombinant CDMP-1, CDMP-2 and OP-1. Phenotypic analysis indicate that periosteum
      derived cell populations prepared, expanded, and cultured under the conditions
      described below, constitutively express messenger RNAs for the bone markers
      osteocalcin, osteopontin and collagen type I, and the chondrogenic markers
      collagen type II and aggrecan as determined by RT-PCR. Moreover, histologic
      examinations showed positive staining for alcian blue and alkaline phosphatase
      (AP). Treatment of periosteum-derived cells with CDMPs and OP-1 resulted in a
      dose-dependent increase of cell proliferation; CDMP-2 was less active in this
      regard. Furthermore, all growth factors enhanced osteogenic differentiation as
      assessed by a time- and dose-dependent stimulation of AP activity and OP-1
      increased messenger RNA expression for osteocalcin and collagen type I. We
      further examined the effects of CDMPs and OP-1 on chondrogenic differentiation of
      periosteum-derived cells. Both CDMPs and OP-1 stimulated (35)S-sulfate
      incorporation into newly synthesized macromolecules with OP-1 having a more
      pronounced stimulatory effect when compared with CDMP-1 and CDMP-2. Our results
      indicate that distinct members of the BMP-family increase the mitotic and
      metabolic activity of periosteum-derived cells. The enhancement of both the
      chondrogenic and osteogenic differentiation suggests that these growth factors
      might contribute to the local regulation of bone formation and fracture repair.

PMID- 11316777
TI  - Synchronized exocytotic bursts from gonadotropin-releasing hormone-expressing
      cells: dual control by intrinsic cellular pulsatility and gap junctional
      communication.
AB  - Periodic secretion of GnRH from the hypothalamus is the driving force for the
      release of gonadotropic hormones from the pituitary, but the roles of individual
      neurons in the context of this pulse generator are not known. In this study we
      used FM1-43 to monitor the membrane turnover associated with exocytosis in single
      GT1-7 neurons and found an intrinsic secretory pulsatility (frequency, 1.4 +/-
      0.1/h; pulse duration, 17.3 +/- 0.6 min) that, during time in culture, became
      progressively synchronized among neighboring cells. Voltage-gated calcium
      channels and gap junctional communication each played a major role in
      synchronized pulsatility. An L-type calcium channel inhibitor, nimodipine,
      abolished synchronized pulsatility. In addition, functional gap junction
      communication among adjacent cells was detected, but only under conditions where
      pulsatile synchronization was also observed, and the gap junction inhibitor
      octanol abolished both without affecting pulse frequency or duration. Our
      results, therefore, provide strong evidence that the GnRH pulse generator in GT1
      7 cells arises from a single cell oscillator mechanism that is synchronized
      through network signaling involving voltage-gated calcium channels and gap
      junctions.

PMID- 11316778
TI  - A conditional tetracycline-regulated increase in Gamma amino butyric acid
      production near luteinizing hormone-releasing hormone nerve terminals disrupts
      estrous cyclicity in the rat.
AB  - Gamma amino butyric acid (GABA) is the main inhibitory neurotransmitter
      controlling LH-releasing hormone (LHRH) secretion in the mammalian hypothalamus.
      Whether alterations in GABA homeostasis within discrete regions of the
      neuroendocrine brain known to be targets of GABA action, such as the median
      eminence, can disrupt the ability of the LHRH releasing system to maintain
      reproductive cyclicity is not known but amenable to experimental scrutiny. The
      present experiments were undertaken to examine this issue. Immortalized BAS-8.1
      astroglial cells were genetically modified by infection with a regulatable
      retroviral vector to express the gene encoding the GABA synthesizing enzyme
      glutamic acid decarboxylase-67 (GAD-67) under the control of a tetracycline (tet)
      controlled gene expression system. In this system, expression of the gene of
      interest is repressed by tet and activated in the absence of the antibiotic. BAS
      8.1 cells carrying this regulatory cassette, and cultured in the absence of tet
      ("GAD on"), expressed abundant levels of GAD-67 messenger RNA and GAD enzymatic
      activity, and released GABA when challenged with glutamate. All of these
      responses were inhibited within 24 h of exposure to tet ("GAD off"). Grafting
      "GAD on" cells into the median eminence of late juvenile female rats, near LHRH
      nerve terminals, did not affect the age at vaginal opening, but greatly disrupted
      subsequent estrous cyclicity. These animals exhibiting long periods of persistent
      estrus, interrupted by occasional days in proestrus and diestrus, suggesting the
      occurrence of irregular ovulatory episodes. Administration of the tetracycline
      analog doxycycline (DOXY) in the drinking water inhibited GAD-67synthesis and
      restored estrous cyclicity to a pattern indistinguishable from that of control
      rats grafted with native BAS-8.1 cells. Animals carrying "GAD on" cells showed a
      small increase in serum LH and estradiol levels, and a marked elevation in serum
      androstenedione, all of which were obliterated by turning GAD-67 synthesis off in
      the grafted cells. Morphometric analysis of the ovaries revealed that both groups
      grafted with GABA-producing cells had an increased incidence of large antral
      follicles (>500 micrometer) compared with animals grafted with native BAS-8.1
      cells, but that within this category the incidence of steroidogenically more
      active follicles (i.e. larger than 600 micrometer) was greater in "GAD on" than
      in "GAD off" rats. These results indicate that a regionally discrete, temporally
      controlled increase in GABA availability to LHRH nerve terminals in the median
      eminence of the hypothalamus suffices to disrupt estrous cyclicity in the rat,
      and raise the possibility that similar local alterations in GABA homeostasis may
      contribute to the pathology of hypothalamic amenorrhea/oligomenorrhea in humans.

PMID- 11316779
TI  - Increase in beta-cell mass in transplanted porcine neonatal pancreatic cell
      clusters is due to proliferation of beta-cells and differentiation of duct cells.
AB  - A 20-fold increase in beta-cell mass has been found after transplantation of
      porcine neonatal pancreatic cell clusters (NPCCs). Here the mechanisms leading to
      this increased beta-cell mass were studied. NPCCs (4000 islet equivalents)
      generated after 8 days culture of digested neonatal pig pancreas were
      transplanted beneath the renal capsule of streptozotocin (STZ) diabetic and
      normoglycemic nude mice. Grafts were removed at 10 days, 6 weeks, and 20 weeks
      after transplantation for immunostaining and insulin content. Proliferation of
      beta-cells and duct cells was assessed morphometrically using double
      immunostaining for Ki-67 with insulin or cytokeratin 7 (CK7). Graft maturation
      was assessed with double immunostaining of CK7 and insulin. Apoptosis was
      determined using propidium iodide staining. beta-cell proliferation in NPCCs was
      higher after 8 days of culture compared with that found in neonatal pig pancreas.
      After transplantation, beta-cell proliferation remained high at 10 days,
      decreased somewhat at 6 weeks, and was much lower 20 weeks after transplantation.
      Diabetic recipients not cured at 6 weeks after transplantation had significantly
      higher beta-cell proliferation compared with those cured and to normoglycemic
      recipients. The size of individual beta-cells, as determined by cross-sectional
      area, increased as the grafts matured. Graft insulin content was 20-fold
      increased at 20 weeks after transplantation compared with 8 days cultured NPCCS:
      The proliferation index of duct cells was significantly higher in neonatal pig
      pancreas than in 8 days cultured NPCCs and in 10-day-old grafts. The incidence of
      apoptosis in duct cells appeared to be low. About 20% of duct cells 10 days post
      transplantation showed costaining for CK7 and insulin, a marker of
      protodifferentiation. In conclusion, the increase in beta-cell mass after
      transplantation of NPCCs is due to both proliferation of differentiated beta
      cells and differentiation of duct cells into beta-cells.

PMID- 11316780
TI  - The type 2 iodothyronine deiodinase is expressed in the rat uterus and induced
      during pregnancy.
AB  - Thyroid hormones are of considerable importance for vertebrate reproductive
      function and during development. To further assess the role of these compounds in
      this capacity, we examined the expression pattern of the type 2 iodothyronine
      deiodinase (D2), which converts T(4) to the more active hormone T(3), in the rat
      uterus in both the nonpregnant and the pregnant state. D2 activity was identified
      as the predominant, if not only, 5'-deiodinase in the nonpregnant rat uterus. The
      expression of D2 messenger RNA was located by in situ hybridization to the
      endometrial stromal cells, where the signal was particularly enriched in the
      region adjacent to the epithelial cells of the uterine lumen. During pregnancy,
      D2 activity increased, peaking on day 17 of gestation (embryonic day 17). At that
      time, uterine D2 activity exceeded that in the placenta, as well as that in the
      fetal tissues. In the earlier stages of pregnancy before placental formation
      (e.g. embryonic days 10-11), D2 messenger RNA in the rat uterus was located
      outside the decidual tissue, which was observed, as in previous studies, to
      highly express the inactivating type 3 deiodinase. In summary, the rat uterus,
      particularly during pregnancy, seems to be a site of active thyroid hormone
      metabolism, presumably designed to maintain the optimal thyroid hormone
      environment for both the fetus and the maternal uterine tissue.

PMID- 11316781
TI  - Mrp3, a mitogen-regulated protein/proliferin gene expressed in wound healing and
      in hair follicles.
AB  - During cutaneous wound healing, a marked increase in the local expression of
      growth factors results in increased migration and proliferation of the cells
      responsible for tissue repair. The mitogen-regulated protein (MRP)/proliferin
      proteins are growth factors and angiogenesis factors. Here it is demonstrated
      that Mrp3 is induced in wound edge keratinocytes during cutaneous wound healing
      and also temporally appears in the outer root sheath of the hair follicle during
      the late anagen phase of the hair cycle. In cultured keratinocytes, Mrp3 is
      induced by keratinocyte growth factor, but not by epidermal growth factor or by
      transforming growth factor type alpha. Transgenic mice, expressing lacZ under the
      combined control of the cytomegalovirus immediate early enhancer and the Mrp3
      flanking sequences, demonstrate wound- and hair cycle-induced transgene
      expression. These results show that elements within the flanking regulatory
      sequences of the Mrp3 gene are involved in the activation of Mrp3 in response to
      these events. The results reported here suggest that MRP3 may participate in
      wound healing and hair follicle cycle as a growth factor and/or angiogenesis
      factor.

PMID- 11316782
TI  - Rodent PSP94 gene expression is more specific to the dorsolateral prostate and
      less sensitive to androgen ablation than probasin.
AB  - To date, the rodent ventral prostate (VP) has been the focus of many studies on
      androgen action, less attention has been directed to the lateral prostate (LP)
      and the dorsal prostate (DP). The rodent VP has no clear homologous counterpart
      in the human prostate. The rodent LP and DP is the only prostate lobe comparable
      to the peripheral zone of the human prostate, where hormone-induced prostate
      cancer mainly occurs. To explore its utility for prostate targeting, we have
      studied the gene expression of PSP94 with rat probasin (rPB), a gene commonly
      used for prostate targeting in prostate cancer research and a gene typically
      responsive to androgen regulation. Firstly, we demonstrated PSP94 gene
      transcription being more specific to the LP and DP lobes than rPB, where rPB RNA
      was detected in the LP and DP and other lobes at different levels. Secondly, we
      found that PSP94 gene transcription decreased relatively slowly in response to
      androgen deprivation but recovered rapidly in response to testosterone
      replacement after complete ablation of PSP94 transcription. In the VP, gene
      transcripts of rPB were specifically responsive to androgen deprivation; however,
      they responded relatively slowly in the LP and DP. RNase protection experiments
      indicated that the slow response was not due to abnormal persistence of PSP94
      messenger RNA specifically in the DP and LP lobes in comparison with rPB.
      Thirdly, Western blot analysis revealed that both PSP94 and rPB expression is
      specific to the LP and DP at the protein level, exhibiting slow responses to
      testosterone replacement after castration. We conclude that PSP94 gene expression
      at the transcriptional level is more specific to the LP and DP than rPB and thus
      less sensitive to androgen ablation. This may have clinical implications for
      strategies to target the prostate in cancer therapy.

PMID- 11316783
TI  - Mutagenesis of basic amino acids in the carboxyl-terminal region of insulin-like
      growth factor binding protein-5 affects acid-labile subunit binding.
AB  - Like insulin-like growth factor binding protein-3 (IGFBP-3), IGFBP-5 was recently
      shown to form ternary complexes with insulin-like growth factor (IGF) and the
      acid-labile subunit (ALS). Previous studies using IGFBP-5/IGFBP-6 chimeric
      proteins have identified major and minor ALS binding sites in the carboxyl
      terminal and central regions, respectively of IGFBP-5. We now report that ALS
      binds to IGFBP-3 (K(a) = 1.1 +/- 0.1 liters/nmol) and IGFBP-5 (K(a) = 1.8 +/- 0.5
      liters/nmol) with similar binding affinities. Using site-specific mutants, we
      have identified residues K(211)/R(214)/K(217)/R(218) within the carboxyl-terminal
      region of IGFBP-5 as being essential for ALS binding. Mutation of K(134)R(136) or
      K(138)K(139) in the central region of IGFBP-5 resulted in a small decrease in ALS
      binding.

PMID- 11316784
TI  - Oviductin (Muc9) is expressed in rabbit endocervix.
AB  - While isolating and characterizing cervical mucin glycoproteins, oviductin (Muc9)
      was identified in the rabbit endocervix. Following tissue homogenization,
      endocervical proteins were fractionated by exclusion chromatography (Sepharose CL
      4B). High molecular weight components of the void volume were resolved by density
      gradient centrifugation using cesium bromide and dissociative conditions (4 M
      guanidinium chloride). High density fractions (rho = 1.40 - 1.56 g/ml) were
      deglycosylated with anhydrous trifluoromethane sulfonic acid and sent to Harvard
      Microchemistry where in situ digestion and tryptic peptide separation were
      performed. Out of an HPLC map, microsequence (KLIMGFPTYGR) from peak 51 was 100%
      identical to mouse oviductin, and microsequence (KSTGHNFPLP) from peak 70 was 90%
      identical to hamster oviductin. Temporal expression of oviductin transcripts (2.4
      kilobase) was negligible during the first three months of postnatal cervical
      differentiation. Transcripts were minimally detectable in the cervices of 4-month
      old juveniles. Strong expression in the endocervices of adults was eliminated by
      ovariectomy and restored by estrogen treatment. The presence of oviductin in the
      rabbit endocervix indicates this glycoprotein may have multiple functions, and it
      can no longer be considered oviduct-specific.

PMID- 11316785
TI  - Pregnancy-associated plasma protein-a is the insulin-like growth factor binding
      protein-4 protease secreted by human ovarian granulosa cells and is a marker of
      dominant follicle selection and the corpus luteum.
AB  - Insulin-like growth factors (IGFs), IGF binding proteins (IGFBPs), and IGFBP
      proteases are important in ovarian function. IGFs stimulate granulosa
      steroidogenesis, an effect that is inhibited by IGFBP-4 and augmented by IGFBP-4
      proteolysis. We have recently identified the IGFBP-4 protease in human ovarian
      follicular fluid (FF) as pregnancy-associated plasma protein-A (PAPP-A). In the
      current study, we identify the IGFBP-4 protease secreted by cultured human
      ovarian granulosa cells as PAPP-A, based on specific immunoinhibition and
      immunodepletion of the IGFBP-4 protease activity with PAPP-A polyclonal
      antibodies and immunorecognition by PAPP-A monoclonal antibodies in ELISA. PAPP-A
      was barely detectable in conditioned media (CM) from granulosa derived from </=9
      mm androgen-dominant follicles, but was secreted by cultured granulosa from
      estrogen-dominant follicles >/=9 mm, coincident with dominant follicle selection,
      and by luteinizing granulosa. PAPP-A levels in CM from the latter did not change
      in response to IGF-II or hCG (100 ng/mL). A naturally occurring inhibitor of PAPP
      A, proform of eosinophil major basic protein (proMBP), was detected by ELISA in
      estrogen-dominant follicular fluid FF, but not in CM from granulosa or
      luteinizing granulosa cells treated with IGF-II (0-200 ng/mL), FSH (0-100 ng/mL)
      or hCG (0-100 ng/mL), suggesting an alternative source (other than granulosa) for
      proMBP, compared to PAPP-A. The data demonstrate granulosa cells as a source of
      PAPP-A in human ovary and suggest that PAPP-A is a marker of ovarian follicle
      selection and corpus luteum formation. In addition the data suggest complex
      regulation of this system in human ovary.

PMID- 11316786
TI  - Beyond the Qs in the polyglutamine diseases.

PMID- 11316787
TI  - Loss of Werner syndrome protein function promotes aberrant mitotic recombination.
AB  - The chromosome 8p11-12 Werner syndrome (WRN ) locus encodes a RecQ helicase
      protein of unknown function that possesses both 3' --> 5' helicase and 3' --> 5'
      exonuclease activities. We show that WRN cell lines display a marked reduction in
      cell proliferation following mitotic recombination, and generate few viable gene
      conversion-type recombinants. These findings indicate that WRN plays a role in
      mitotic recombination, and that a loss of WRN function may promote genetic
      instability and disease via recombination-initiated mitotic arrest, cell death,
      or gene rearrangement.

PMID- 11316788
TI  - EID1, an F-box protein involved in phytochrome A-specific light signaling.
AB  - To perceive red and far-red light, plants have evolved specific photoreceptors
      called phytochromes. Even though the spectral properties of all phytochromes are
      very similar, they show a distinct mode of action. Here we describe EID1, a
      negatively acting component of the signaling cascade that shifts the
      responsiveness of the phytochrome A (phyA) signaling system associated with
      hypocotyl elongation from red to far-red wavelengths. EID1 is a novel nuclear F
      box protein that contains a leucine zipper whose integrity is necessary for its
      biological function. EID1 most probably acts by targeting activated components of
      the phyA signaling pathway to ubiquitin-dependent proteolysis.

PMID- 11316789
TI  - Roles of yeast DNA polymerases delta and zeta and of Rev1 in the bypass of abasic
      sites.
AB  - Abasic (AP) sites are one of the most frequently formed lesions in DNA, and they
      present a strong block to continued synthesis by the replicative DNA machinery.
      Here we show efficient bypass of an AP site by the combined action of yeast DNA
      polymerases delta and zeta. In this reaction, Poldelta inserts an A nucleotide
      opposite the AP site, and Polzeta subsequently extends from the inserted
      nucleotide. Consistent with these observations, sequence analyses of mutations in
      the yeast CAN1s gene indicate that A is the nucleotide inserted most often
      opposite AP sites. The nucleotides C, G, and T are also incorporated, but much
      less frequently. Enzymes such as Rev1 and Poleta may contribute to the insertion
      of these other nucleotides; the predominant role of Rev1 in AP bypass, however,
      is likely to be structural. Steady-state kinetic analyses show that Polzeta is
      highly inefficient in incorporating nucleotides opposite the AP site, but it
      efficiently extends from nucleotides, particularly an A, inserted opposite this
      lesion. Thus, in eukaryotes, bypass of an AP site requires the sequential action
      of two DNA polymerases, wherein the extension step depends solely upon Polzeta,
      but the insertion step can be quite varied, involving not only the predominant
      action of the replicative DNA polymerase, Poldelta, but also the less prominent
      role of various translesion synthesis polymerases.

PMID- 11316790
TI  - Conversion of a gene-specific repressor to a regional silencer.
AB  - In Saccharomyces cerevisiae, gene silencing at the HMR and HML loci is normally
      dependent on Sir2p, Sir3p, and Sir4p, which are structural components of silenced
      chromatin. Sir2p is a NAD+-dependent histone deacetylase required for silencing.
      Silencing can be restored in cells lacking Sir proteins by a dominant mutation in
      SUM1, which normally acts as a mitotic repressor of meiotic genes. This study
      found that mutant Sum1-1p, but not wild-type Sum1p, associated directly with HM
      loci. The origin recognition complex (ORC) was required for Sum1-1p-mediated
      silencing, and mutations in ORC genes reduced association of Sum1-1p with the HM
      loci. Sum1-1p-mediated silencing also depended on HST1, a paralog of SIR2. Both
      Sum1-1p and wild-type Sum1p interacted with Hst1p in coimmunoprecipitation
      experiments. Therefore, the SUM1-1 mutation did not change the affinity of Sum1p
      for Hst1p, but rather relocalized Sum1p to the HM loci. Sum1-1-Hst1p action led
      to hypoacetylation of the nucleosomes at HM loci. Thus, Sum1-1p and Hst1p could
      substitute for Sir proteins to achieve silencing through formation of a
      compositionally distinct type of heterochromatin.

PMID- 11316791
TI  - The NF2 tumor suppressor gene product, merlin, mediates contact inhibition of
      growth through interactions with CD44.
AB  - The neurofibromatosis-2 (NF2) gene encodes merlin, an ezrin-radixin-moesin-(ERM)
      related protein that functions as a tumor suppressor. We found that merlin
      mediates contact inhibition of growth through signals from the extracellular
      matrix. At high cell density, merlin becomes hypo-phosphorylated and inhibits
      cell growth in response to hyaluronate (HA), a mucopolysaccharide that surrounds
      cells. Merlin's growth-inhibitory activity depends on specific interaction with
      the cytoplasmic tail of CD44, a transmembrane HA receptor. At low cell density,
      merlin is phosphorylated, growth permissive, and exists in a complex with ezrin,
      moesin, and CD44. These data indicate that merlin and CD44 form a molecular
      switch that specifies cell growth arrest or proliferation.

PMID- 11316792
TI  - Analysis of the transcriptional program induced by Raf in epithelial cells.
AB  - Activation of the Raf/MAP kinase pathway is a critical event in tumorigenesis
      induced by RAS and other oncogenes, a major role of this signaling system being
      the regulation of cellular transcription factors. To address the contribution of
      MAP kinase mediated transcriptional changes to the transformed phenotype, we used
      an inducible form of Raf to analyze early changes in the transcription of some
      6000 genes following activation of the kinase in a normal human breast epithelial
      cell line. Of the more than 120 significant changes in mRNA level detected, genes
      promoting cell proliferation, invasiveness, and angiogenesis featured
      prominently. Some of the most strongly induced genes encoded growth factors of
      the EGF family: Autocrine activation of the EGF receptor was shown to be
      responsible for the ability of Raf activation to protect these cells from
      apoptosis induced by detachment of cells from extracellular matrix (anoikis),
      which is a critical component of the transformed phenotype.

PMID- 11316793
TI  - Antagonistic role of E4BP4 and PAR proteins in the circadian oscillatory
      mechanism.
AB  - E4BP4, a basic leucine zipper transcription factor, contains a DNA-binding domain
      closely related to DBP, HLF, and TEF, which are PAR proteins. Here, we show that
      the phase of e4bp4 mRNA rhythm is opposite to that of the dbp, hlf, and tef
      rhythms in the suprachiasmatic nucleus (SCN), the mammalian circadian center, and
      the liver. The protein levels of E4BP4 and DBP also fluctuate in almost the
      opposite phase. Moreover, all PAR proteins activate, whereas E4BP4 suppresses,
      the transcriptional activity of the reporter gene containing a common binding
      sequence in transcriptional assays in vitro. An electrophoretic mobility shift
      assay demonstrated that E4BP4 is not able to dimerize with the PAR proteins, but
      is able to compete for the same binding sites with them. Furthermore, we showed
      sustained low e4bp4 and high dbp mRNA levels in mCry-deficient mice. These
      results indicate that the E4BP4 and PAR proteins are paired components of a
      reciprocating mechanism wherein E4BP4 suppresses the transcription of target
      genes during the time of day when E4BP4 is abundant, and the PAR proteins
      activate them at another time of day. E4BP4 and the PAR proteins may switch back
      and forth between the on-off conditions of the target genes.

PMID- 11316794
TI  - Recruitment of the transcriptional machinery through GAL11P: structure and
      interactions of the GAL4 dimerization domain.
AB  - The GAL4 dimerization domain (GAL4-dd) is a powerful transcriptional activator
      when tethered to DNA in a cell bearing a mutant of the GAL11 protein, named
      GAL11P. GAL11P (like GAL11) is a component of the RNA-polymerase II holoenzyme.
      Nuclear magnetic resonance (NMR) studies of GAL4-dd revealed an elongated dimer
      structure with C(2) symmetry containing three helices that mediate dimerization
      via coiled-coil contacts. The two loops between the three coiled coils form
      mobile bulges causing a variation of twist angles between the helix pairs.
      Chemical shift perturbation analysis mapped the GAL11P-binding site to the C
      terminal helix alpha3 and the loop between alpha1 and alpha2. One GAL11P monomer
      binds to one GAL4-dd dimer rendering the dimer asymmetric and implying an extreme
      negative cooperativity mechanism. Alanine-scanning mutagenesis of GAL4-dd showed
      that the NMR-derived GAL11P-binding face is crucial for the novel transcriptional
      activating function of the GAL4-dd on GAL11P interaction. The binding of GAL4 to
      GAL11P, although an artificial interaction, represents a unique structural motif
      for an activating region capable of binding to a single target to effect gene
      expression.

PMID- 11316795
TI  - Developmental regulation of transcription by a tissue-specific TAF homolog.
AB  - Alternate forms of the general transcription machinery have been described in
      several tissues or cell types. However, the role of tissue-specific TBP
      associated factors (TAF(II)s) and other tissue-specific transcription components
      in regulating differential gene expression during development was not clear. Here
      we show that the cannonball gene of Drosophila encodes a cell type-specific
      homolog of a more ubiquitously expressed component of the general transcription
      factor TFIID. cannonball is required in vivo for high level transcription of a
      set of stage- and tissue-specific target genes during male gametogenesis.
      Regulation of transcription by cannonball is absolutely required for
      spermatogenesis, as null mutations block meiotic cell cycle progression and
      result in a complete failure of spermatid differentiation. Our results
      demonstrate that cell type-specific TAF(II)s play an important role in
      developmental regulation of gene expression.

PMID- 11316797
TI  - Multiple regions within the coxsackievirus and adenovirus receptor cytoplasmic
      domain are required for basolateral sorting.
AB  - The coxsackievirus and adenovirus receptor (CAR) mediates attachment and
      infection by coxsackie B viruses and many adenoviruses. In human airway
      epithelia, as well as in transfected Madin-Darby canine kidney cells, CAR is
      expressed exclusively on the basolateral surface. Variants of CAR that lack the
      cytoplasmic domain or are attached to the cell membrane by a
      glycosylphosphatidylinositol anchor are expressed on both the apical and
      basolateral surfaces. We have examined the localization of CAR variants with
      progressive truncations of the cytoplasmic domain, as well as with mutations that
      ablate a potential PDZ (PSD95/dlg/ZO-1) interaction motif and a putative tyrosine
      based sorting signal. In addition, we have examined the targeting of two murine
      CAR isoforms, with different C-terminal sequences. The results suggest that
      multiple regions within the CAR cytoplasmic domain contain information that is
      necessary for basolateral targeting.

PMID- 11316798
TI  - Dysbindin, a novel coiled-coil-containing protein that interacts with the
      dystrobrevins in muscle and brain.
AB  - The dystrophin-associated protein complex (DPC) is required for the maintenance
      of muscle integrity during the mechanical stresses of contraction and relaxation.
      In addition to providing a membrane scaffold, members of the DPC such as the
      alpha-dystrobrevin protein family are thought to play an important role in
      intracellular signal transduction. To gain additional insights into the function
      of the DPC, we performed a yeast two-hybrid screen for dystrobrevin-interacting
      proteins. Here we describe the identification of a dysbindin, a novel
      dystrobrevin-binding protein. Dysbindin is an evolutionary conserved 40-kDa
      coiled-coil-containing protein that binds to alpha- and beta-dystrobrevin in
      muscle and brain. Dystrophin and alpha-dystrobrevin are co-immunoprecipitated
      with dysbindin, indicating that dysbindin is DPC-associated in muscle. Dysbindin
      co-localizes with alpha-dystrobrevin at the sarcolemma and is up-regulated in
      dystrophin-deficient muscle. In the brain, dysbindin is found primarily in axon
      bundles and especially in certain axon terminals, notably mossy fiber synaptic
      terminals in the cerebellum and hippocampus. These findings have implications for
      the molecular pathology of Duchenne muscular dystrophy and may provide an
      alternative route for anchoring dystrobrevin and the DPC to the muscle membrane.

PMID- 11316796
TI  - PIE-1 is a bifunctional protein that regulates maternal and zygotic gene
      expression in the embryonic germ line of Caenorhabditis elegans.
AB  - The CCCH zinc finger protein PIE-1 is an essential regulator of germ cell fate
      that segregates with the germ lineage during the first cleavages of the
      Caenorhabditis elegans embryo. We have shown previously that one function of PIE
      1 is to inhibit mRNA transcription. Here we show that PIE-1 has a second function
      in germ cells; it is required for efficient expression of the maternally encoded
      Nanos homolog NOS-2. This second function is genetically separable from PIE-1's
      inhibitory effect on transcription. A mutation in PIE-1's second CCCH finger
      reduces NOS-2 expression without affecting transcriptional repression and causes
      primordial germ cells to stray away from the somatic gonad, occasionally exiting
      the embryo entirely. Our results indicate that PIE-1 promotes germ cell fate by
      two independent mechanisms as follows: (1) inhibition of transcription, which
      blocks zygotic programs that drive somatic development, and (2) activation of
      protein expression from nos-2 and possibly other maternal RNAs, which promotes
      primordial germ cell development.

PMID- 11316799
TI  - Caveolin-1 and caveolin-2 expression in mouse macrophages. High density
      lipoprotein 3-stimulated secretion and a lack of significant subcellular co
      localization.
AB  - Evidence for caveolin expression in macrophages is scarce and conflicting. We
      therefore examined caveolin-1 and caveolin-2 expression in resident and
      thioglycollate-elicited mouse peritoneal macrophages (tg-MPM) and in the J774
      mouse macrophage cell line by RT-PCR, ribonuclease protection assay,
      immunoblotting, and immunofluorescence. We found that relative to 3T3 cells,
      resident MPM and tg-MPM express low amounts of caveolin-1 (45 and 15% of those in
      3T3 fibroblasts, respectively), while J774.A1 cells do not express any. Caveolin
      2, on the other hand, is expressed in all cells examined, with highest expression
      in tg-MPM and the lowest in J774 cells. The relative levels of caveolin
      expression in the various cells correspond well with their respective mRNA
      levels, as measured by ribonuclease protection assay. Caveolin-1, present
      primarily on the cell surface, does not co-localize significantly with caveolin
      2, which is present primarily in the Golgi compartment in all macrophages
      studied. Loading of tg-MPM with cholesterol or variations in unesterified
      cholesterol content appear to have little effect on the level of caveolin-1 or -2
      expression or their distribution. Stimulation of cholesterol efflux by HDL(3)
      leads to caveolin-1 and caveolin-2 secretion to the cell culture medium, a
      process not detected in the absence of HDL(3). The lack of significant co
      localization of the two caveolin isoforms in primary macrophages and their
      secretion in the presence of HDL(3) provides an interesting and physiologically
      relevant model system to study additional aspects of caveolin function.

PMID- 11316800
TI  - Structural and energetic characteristics of the heparin-binding site in
      antithrombotic protein C.
AB  - Human activated protein C (APC) is a key component of a natural anticoagulant
      system that regulates blood coagulation. In vivo, the catalytic activity of APC
      is regulated by two serpins, alpha1-antitrypsin and the protein C inhibitor
      (PCI), the inhibition by the latter being stimulated by heparin. We have
      identified a heparin-binding site in the serine protease domain of APC and
      characterized the energetic basis of the interaction with heparin. According to
      the counter-ion condensation theory, the binding of heparin to APC is 66% ionic
      in nature and comprises four to six net ionic interactions. To localize the
      heparin-binding site, five recombinant APC variants containing amino acid
      exchanges in loops 37, 60, and 70 (chymotrypsinogen numbering) were created. As
      demonstrated by surface plasmon resonance, reduction of the electropositive
      character of loops 37 and 60 resulted in complete loss of heparin binding. The
      functional consequence was loss in heparin-induced stimulation of APC inhibition
      by PCI, whereas the PCI-induced APC inhibition in the absence of heparin was
      enhanced. Presumably, the former observations were due to the inability of
      heparin to bridge some APC mutants to PCI, whereas the increased inhibition of
      certain APC variants by PCI in the absence of heparin was due to reduced
      repulsion between the enzymes and the serpin. The heparin-binding site of APC was
      also shown to interact with heparan sulfate, albeit with lower affinity. In
      conclusion, we have characterized and spatially localized the functionally
      important heparin/heparan sulfate-binding site of APC.

PMID- 11316801
TI  - The role of toll-like receptors (TLRs) in bacteria-induced maturation of murine
      dendritic cells (DCS). Peptidoglycan and lipoteichoic acid are inducers of DC
      maturation and require TLR2.
AB  - Toll-like receptors (TLRs) have been found to be key elements in pathogen
      recognition by the host immune system. Dendritic cells (DCs) are crucial for both
      innate immune responses and initiation of acquired immunity. Here we focus on the
      potential involvement of TLR ligand interaction in DC maturation. TLR2 knockout
      mice and mice carrying a TLR4 mutation (C3H/HeJ) were investigated for DC
      maturation induced by peptidoglycan (PGN), lipopolysaccharide (LPS), or
      lipoteichoic acids (LTAs). All stimuli induced maturation of murine bone marrow
      derived DCs in control mice. TLR2(-)/- mice lacked maturation upon stimulation
      with PGN, as assessed by expression of major histocompatibility complex class II,
      CD86, cytokine, and chemokine production, fluorescein isothiocyanate-dextran
      uptake, and mixed lymphocyte reactions, while being completely responsive to LPS.
      A similar lack of maturation was observed in C3H/HeJ mice upon stimulation with
      LPS. DC maturation induced by LTAs from two different types of bacteria was
      severely impaired in TLR2(-)/-, whereas C3H/HeJ mice responded to LTAs in a
      manner similar to wild-type mice. We demonstrate that DC maturation is induced by
      stimuli from Gram-positive microorganisms, such as PGN and LTA, with similar
      efficiency as by LPS. Finally, we provide evidence that TLR2 and TLR4 interaction
      with the appropriate ligand is essential for bacteria-induced maturation of DCs.

PMID- 11316802
TI  - The stimulation of inducible nitric-oxide synthase by the prion protein fragment
      106--126 in human microglia is tumor necrosis factor-alpha-dependent and involves
      p38 mitogen-activated protein kinase.
AB  - A synthetic peptide consisting of amino acid residues 106-126 of the human prion
      protein (PrP-(106--126)) has been previously demonstrated to be neurotoxic and to
      induce microglial activation. The present study investigated the expression of
      the inducible form of the nitric-oxide synthase (NOS-II) in human microglial
      cells treated with PrP-(106--126). Using reverse transcriptase-polymerase chain
      reaction, we found that PrP-(106--126) induces NOS-II gene expression after 24 h
      of treatment and that this effect is accompanied by a peak of nuclear factor
      kappa B (NF-kappa B) binding at 30 min as evaluated by electrophoretic mobility
      shift assay. Since our previous data demonstrated tumor necrosis factor-alpha
      (TNF-alpha) to be a potent inducer of NOS-II in these cells, we analyzed the
      expression of this cytokine in PrP-(106--126)-treated microglia. PrP-(106--126)
      caused the release of TNF-alpha as detected by enzyme-linked immunosorbent assay,
      and a blocking antibody, anti-TNF-alpha, abolished NOS-II induction elicited by
      this peptide. Moreover, PrP-(106-126) activates p38 mitogen-activated protein
      kinase, and the inhibition of this pathway determines the ablation of NF-kappa B
      binding induced by this fragment peptide.

PMID- 11316803
TI  - DnaA box sequences as the site for helicase delivery during plasmid RK2
      replication initiation in Escherichia coli.
AB  - DnaA box sequences are a common motif present within the replication origin
      region of a diverse group of bacteria and prokaryotic extrachromosomal genetic
      elements. Although the origin opening caused by binding of the host DnaA protein
      has been shown to be critical for the loading of the DnaB helicase, to date there
      has been no direct evidence presented for the formation of the DnaB complex at
      the DnaA box site. For these studies, we used the replication origin of plasmid
      RK2 (oriV), containing a cluster of four DnaA boxes that bind DnaA proteins
      isolated from different bacterial species (Caspi, R., Helinski, D. R., Pacek, M.,
      and Konieczny, I. (2000) J. Biol. Chem. 275, 18454-18461). Size exclusion
      chromatography, surface plasmon resonance, and electron microscopy experiments
      demonstrated that the DnaB helicase is delivered to the DnaA box region, which is
      localized approximately 200 base pairs upstream from the region of origin opening
      and a potential site for helicase entry. The DnaABC complex was formed on both
      double-stranded superhelical and linear RK2 templates. A strict DnaA box sequence
      requirement for stable formation of that nucleoprotein structure was confirmed.
      In addition, our experiments provide evidence for interaction between the plasmid
      initiation protein TrfA and the DnaABC prepriming complex, formed at DnaA box
      region. This interaction is facilitated via direct contact between TrfA and DnaB
      proteins.

PMID- 11316804
TI  - c-Jun binds the N terminus of human TAF(II)250 to derepress RNA polymerase II
      transcription in vitro.
AB  - c-Jun is an oncoprotein that activates transcription of many genes involved in
      cell growth and proliferation. We studied the mechanism of transcriptional
      activation by human c-Jun in a human RNA polymerase II transcription system
      composed of highly purified recombinant and native transcription factors.
      Transcriptional activation by c-Jun depends on the TATA-binding protein (TBP)
      associated factor (TAF) subunits of transcription factor IID (TFIID). Protein
      protein interaction assays revealed that c-Jun binds with high specificity to the
      largest subunit of human TFIID, TAF(II)250. The region of TAF(II)250 bound by c
      Jun lies in the N-terminal 163 amino acids. This same region of TAF(II)250 binds
      to TBP and represses its interaction with TATA boxes, thereby decreasing DNA
      binding by TFIID. We hypothesized that c-Jun is capable of derepressing the
      effect of the TAF(II)250 N terminus on TFIID-driven transcription. In support of
      this hypothesis, we found that c-Jun increased levels of TFIID-driven
      transcription in vitro when added at high concentrations to a DNA template
      lacking activator protein 1 (AP-1) sites. Moreover, c-Jun blocked the repression
      of TBP DNA binding caused by the N terminus of TAF(II)250. In addition to
      revealing a mechanism by which c-Jun activates transcription, our studies provide
      the first evidence that an activator can bind directly to the N terminus of
      TAF(II)250 to derepress RNA polymerase II transcription in vitro.

PMID- 11316805
TI  - Reaction mechanism from leucoanthocyanidin to anthocyanidin 3-glucoside, a key
      reaction for coloring in anthocyanin biosynthesis.
AB  - In the conversion from colorless leucoanthocyanidin to colored anthocyanidin 3
      glucoside, at least two enzymes, anthocyanidin synthase (ANS) and UDP
      glucose:flavonoid 3-O-glucosyltransferase (3-GT), are postulated to be involved.
      Despite the importance of this reaction sequence for coloring in anthocyanin
      biosynthesis, the biochemical reaction mechanism has not been clarified, and the
      possible involvement of a dehydratase has not been excluded. Here we show that
      recombinant ANSs from several model plant species, snapdragon, petunia, torenia,
      and maize, catalyze the formation of anthocyanidin in vitro through a 2
      oxoglutarate-dependent oxidation of leucoanthocyanidin. Crude extracts of
      Escherichia coli, expressing recombinant ANSs from these plant species, and
      purified recombinant enzymes of petunia and maize catalyzed the formation of
      anthocyanidin in the presence of ferrous ion, 2-oxoglutarate, and ascorbate. The
      in vitro formation of colored cyanidin 3-glucoside from leucocyanidin, via a
      cyanidin intermediate, was demonstrated using petunia ANS and 3-GT. The entire
      reaction sequence did not require any additional dehydratase but was dependent on
      moderate acidic pH conditions following the enzymatic steps. The present study
      indicated that the in vivo cytosolic reaction sequence involves an ANS-catalyzed
      2-oxoglutarate-dependent conversion of leucoanthocyanidin (flavan-3,4-cis-diol)
      to 3-flaven-2,3-diol (pseudobase), most probably through 2,3-desaturation and
      isomerization, followed by glucosylation at the C-3 position by 3-GT.

PMID- 11316806
TI  - Amyloid-beta induces chemotaxis and oxidant stress by acting at formylpeptide
      receptor 2, a G protein-coupled receptor expressed in phagocytes and brain.
AB  - Amyloid-beta, the pathologic protein in Alzheimer's disease, induces chemotaxis
      and production of reactive oxygen species in phagocytic cells, but mechanisms
      have not been fully defined. Here we provide three lines of evidence that the
      phagocyte G protein-coupled receptor (N-formylpeptide receptor 2 (FPR2)) mediates
      these amyloid-beta-dependent functions in phagocytic cells. First, transfection
      of FPR2, but not related receptors, including the other known N-formylpeptide
      receptor FPR, reconstituted amyloid-beta-dependent chemotaxis and calcium flux in
      HEK 293 cells. Second, amyloid-beta induced both calcium flux and chemotaxis in
      mouse neutrophils (which express endogenous FPR2) with similar potency as in FPR2
      transfected HEK 293 cells. This activity could be specifically desensitized in
      both cell types by preincubation with a specific FPR2 agonist, which desensitizes
      the receptor, or with pertussis toxin, which uncouples it from G(i)-dependent
      signaling. Third, specific and reciprocal desensitization of superoxide
      production was observed when N-formylpeptides and amyloid-beta were used to
      sequentially stimulate neutrophils from FPR -/- mice, which express FPR2
      normally. Potential biological relevance of these results to the
      neuroinflammation associated with Alzheimer's disease was suggested by two
      additional findings: first, FPR2 mRNA could be detected by PCR in mouse brain;
      second, induction of FPR2 expression correlated with induction of calcium flux
      and chemotaxis by amyloid-beta in the mouse microglial cell line N9. Further, in
      sequential stimulation experiments with N9 cells, N-formylpeptides and amyloid
      beta were able to reciprocally cross-desensitize each other. Amyloid-beta was
      also a specific agonist at the human counterpart of FPR2, the FPR-like 1
      receptor. These results suggest a unified signaling mechanism for linking amyloid
      beta to phagocyte chemotaxis and oxidant stress in the brain.

PMID- 11316807
TI  - SopE acts as an Rab5-specific nucleotide exchange factor and recruits non
      prenylated Rab5 on Salmonella-containing phagosomes to promote fusion with early
      endosomes.
AB  - Rab-GTPase regulates the fusion between two specific vesicles. It is well
      documented that, for their biological function, Rab proteins need to be
      prenylated for attachment to the vesicle membrane. In contrast, we showed in the
      present investigation that SopE, a type III secretory protein of Salmonella,
      translocates onto Salmonella-containing phagosomes (LSP) and mediates the
      recruitment of non-prenylated Rab5 (Rab5:DeltaC4) on LSP in GTP form.
      Simultaneously, SopE present in infected cell cytosol acts as an Rab5-specific
      exchange factor and converts the inactive Rab-GDP to the GTP form. The non
      prenylated Rab5 subsequently promoted efficient fusion of LSP with early
      endosomes. This is the first demonstration that a prenylation-deficient Rab
      protein retains biological activity and can promote vesicle fusion, if it is
      recruited on the membrane by some other method.

PMID- 11316808
TI  - Prodomain processing of Asp1 (BACE2) is autocatalytic.
AB  - Generation of the amyloid peptide through proteolytic processing of the amyloid
      precursor protein by beta- and gamma-secretases is central to the etiology of
      Alzheimer's disease. The highly elusive beta-secretase was recently identified as
      a transmembrane aspartic proteinase, Asp2 (BACE). The Asp2 homolog Asp1
      (BACE2/DRAP) has also been reported to exhibit beta-secretase cleavage of amyloid
      precursor protein. Most aspartic proteinases are generated as inactive
      proenzymes, requiring removal of the prodomain to generate active proteinase.
      Here we show that prodomain processing of Asp1 occurs between Leu(62) and Ala(63)
      and is autocatalytic. Asp1 cleaved a maltose-binding protein-Asp1 prodomain
      fusion protein and a synthetic peptide at this site. Mutation of one of the
      conserved catalytic aspartic acid residues in the active site of Asp1 to
      asparagine (D110N) abolished this cleavage. Mutation of P(1)' and P(2)' residues
      in the substrate to phenylalanine reduced cleavage at this site. Asp1 expressed
      in cells was the mature form, and prodomain processing occurred intramolecularly
      within the endoplasmic reticulum/early Golgi. Interestingly, a proportion of
      mature Asp1 was expressed on the cell surface. When full-length Asp1(D110N) was
      expressed in COS-7 cells, it was not processed, suggesting that no other
      proteinase can activate Asp1 in these cells.

PMID- 11316809
TI  - Induction of neuronal cell death by Rab5A-dependent endocytosis of alpha
      synuclein.
AB  - The presynaptic alpha-synuclein is a prime suspect for contributing to Lewy
      pathology and clinical aspects of diseases, including Parkinson's disease,
      dementia with Lewy bodies, and a Lewy body variant of Alzheimer's disease. Here
      we examined the pathogenic mechanism of neuronal cell death induced by alpha
      synuclein. The exogenous addition of alpha-synuclein caused a marked decrease of
      cell viability in primary and immortalized neuronal cells. The neuronal cell
      death appeared to be correlated with the Rab5A-specific endocytosis of alpha
      synuclein that subsequently caused the formation of Lewy body-like
      intracytoplasmic inclusions. This was further supported by the fact that the
      expression of GTPase-deficient Rab5A resulted in a significant decrease of its
      cytotoxicity as a result of incomplete endocytosis of alpha-synuclein.

PMID- 11316810
TI  - The reciprocal role of Egr-1 and Sp family proteins in regulation of the PTP1B
      promoter in response to the p210 Bcr-Abl oncoprotein-tyrosine kinase.
AB  - Protein-tyrosine phosphatase 1B (PTP1B) is an important regulator of protein
      tyrosine kinase-dependent signaling pathways. Changes in expression and activity
      of PTP1B have been associated with various human diseases; however, the
      mechanisms by which PTP1B expression is regulated have yet to be characterized.
      Previously, we have shown that the expression of PTP1B is enhanced by p210 Bcr
      Abl and that PTP1B is a specific antagonist of transformation induced by this
      oncoprotein protein-tyrosine kinase. Here we have characterized the PTP1B
      promoter and demonstrate that a motif with features of a stress-response element
      acts as a p210 Bcr-Abl-responsive sequence, termed PRS. We have shown that three
      C(2)H(2) zinc finger proteins, namely Sp1, Sp3, and Egr-1, bind to PRS. Whereas
      binding of either Sp1 or Sp3 induced promoter function, Egr-1 repressed Sp3
      mediated PTP1B promoter activation. The binding of Egr-1 to PRS is suppressed by
      p210 Bcr-Abl due to the inhibition of Egr-1 expression, resulting in the
      enhancement of PTP1B promoter activity. Our data indicate that Egr-1 and Sp
      family proteins play a reciprocal role in the control of expression from the
      PTP1B promoter.

PMID- 11316811
TI  - Sau3AI, a monomeric type II restriction endonuclease that dimerizes on the DNA
      and thereby induces DNA loops.
AB  - Here, we report that Sau3AI, an unusually large type II restriction enzyme with
      sequence homology to the mismatch repair protein MutH, is a monomeric enzyme as
      shown by gel filtration and ultracentrifugation. Structural similarities in the N
      and C-terminal halves of the protein suggest that Sau3AI is a pseudo-dimer, i.e.
      a polypeptide with two similar domains. Since Sau3AI displays a nonlinear
      dependence of cleavage activity on enzyme concentration and a strong preference
      for substrates with two recognition sites over those with only one, it is likely
      that the functionally active form of Sau3AI is a dimer of a pseudo-dimer. Indeed,
      electron microscopy studies demonstrate that two distant recognition sites are
      brought together through DNA looping induced by the simultaneous binding of two
      Sau3AI molecules to the DNA. We suggest that the dimeric form of Sau3AI supplies
      two DNA-binding sites, one that is associated with the catalytic center and one
      that serves as an effector site.

PMID- 11316812
TI  - Specific structural determinants are responsible for the antioxidant activity and
      the cell cycle effects of resveratrol.
AB  - Resveratrol (3,4',5-trihydroxy-trans-stilbene) is a natural phytoalexin found in
      grapes and wine, which shows antioxidant and antiproliferative activities. In
      this study we have investigated whether these properties are dependent on similar
      or different structural determinants of the molecule. To this purpose,
      resveratrol derivatives, in which all or each single hydroxylic function were
      selectively substituted with methyl groups, were synthesized. Analogues with the
      stilbenic double bond reduced or with the stereoisometry modified were also
      investigated. The antioxidant activity of these compounds was evaluated by
      measuring the inhibition of citronellal thermo-oxidation, or the reduction of 2,2
      diphenyl-1-picrylhydrazyl radical. In addition, the protection against lipid
      peroxidation was determined in rat liver microsomes, and in human primary cell
      cultures. The antiproliferative activity was evaluated by a clonogenic assay, and
      by analysis of cell cycle progression and DNA synthesis. The results showed that
      the hydroxyl group in 4' position is not the sole determinant for antioxidant
      activity. In contrast, the presence of 4'-OH together with stereoisometry in the
      trans-conformation (4'-hydroxystyryl moiety) was absolutely required for
      inhibition of cell proliferation. Enzymatic assays in vitro demonstrated that
      inhibition of DNA synthesis was induced by a direct interaction of resveratrol
      with DNA polymerases alpha and delta.

PMID- 11316813
TI  - Set domain-containing protein, G9a, is a novel lysine-preferring mammalian
      histone methyltransferase with hyperactivity and specific selectivity to lysines
      9 and 27 of histone H3.
AB  - The covalent modification of histone tails has regulatory roles in various
      nuclear processes, such as control of transcription and mitotic chromosome
      condensation. Among the different groups of enzymes known to catalyze the
      covalent modification, the most recent additions are the histone
      methyltransferases (HMTases), whose functions are now being characterized. Here
      we show that a SET domain-containing protein, G9a, is a novel mammalian lysine
      preferring HMTase. Like Suv39 h1, the first identified lysine-preferring
      mammalian HMTase, G9a transfers methyl groups to the lysine residues of histone
      H3, but with a 10-20-fold higher activity. It was reported that lysines 4, 9, and
      27 in H3 are methylated in mammalian cells. G9a was able to add methyl groups to
      lysine 27 as well as 9 in H3, compared with Suv39 h1, which was only able to
      methylate lysine 9. Our data clearly demonstrated that G9a has an enzymatic
      nature distinct from Suv39 h1 and its homologue h2. Finally, fluorescent protein
      labeled G9a was shown to be localized in the nucleus but not in the repressive
      chromatin domains of centromeric loci, in which Suv39 h1 family proteins were
      localized. This finding indicates that G9a may contribute to the organization of
      the higher order chromatin structure of non-centromeric loci.

PMID- 11316814
TI  - Characterization of a novel carotenoid cleavage dioxygenase from plants.
AB  - The plant hormone abscisic acid is derived from the oxidative cleavage of a
      carotenoid precursor. Enzymes that catalyze this carotenoid cleavage reaction,
      nine-cis epoxy-carotenoid dioxygenases, have been identified in several plant
      species. Similar proteins, whose functions are not yet known, are present in
      diverse organisms. A putative cleavage enzyme from Arabidopsis thaliana contains
      several highly conserved motifs found in other carotenoid cleavage enzymes.
      However, the overall homology with known abscisic acid biosynthetic enzymes is
      low. To determine the biochemical function of this protein, it was expressed in
      Escherichia coli and used for in vitro assays. The recombinant protein was able
      to cleave a variety of carotenoids at the 9-10 and 9'-10' positions. In most
      instances, the enzyme cleaves the substrate symmetrically to produce a C(14)
      dialdehyde and two C(13) products, which vary depending on the carotenoid
      substrate. Based upon sequence similarity, orthologs of this gene are present
      throughout the plant kingdom. A similar protein in beans catalyzes the same
      reaction in vitro. The characterization of these activities offers the potential
      to synthesize a variety of interesting, natural products and is the first step in
      determining the function of this gene family in plants.

PMID- 11316815
TI  - Mechanism of rhodopsin activation as examined with ring-constrained retinal
      analogs and the crystal structure of the ground state protein.
AB  - The guanine nucleotide-binding protein (G-protein)-coupled receptor superfamily
      (GPCR) is comprised of a large group of membrane proteins involved in a wide
      range of physiological signaling processes. The functional switch from a
      quiescent to an active conformation is at the heart of GPCR action. The GPCR
      rhodopsin has been studied extensively because of its key role in scotopic
      vision. The ground state chromophore, 11-cis-retinal, holds the transmembrane
      region of the protein in the inactive conformation. Light induces cis-trans
      isomerization and rhodopsin activation. Here we show that rhodopsin regenerated
      with a ring-constrained 11-cis-retinal analog undergoes photoisomerization;
      however, it remains marginally active because isomerization occurs without the
      chromophore-induced conformational change of the opsin moiety. Modeling the
      locked chromophore analogs in the active site of rhodopsin suggests that the beta
      ionone ring rotates but is largely confined within the binding site of the
      natural 11-cis-retinal chromophore. This constraint is a result of the geometry
      of the stable 11-cis-locked configuration of the chromophore analogs. These
      results suggest that the native chromophore cis-trans isomerization is merely a
      mechanism for repositioning of the beta-ionone ring which ultimately leads to
      helix movements and determines receptor activation.

PMID- 11316816
TI  - Degradation of endoplasmic reticulum (ER) quality control substrates requires
      transport between the ER and Golgi.
AB  - Endoplasmic reticulum (ER) quality control (ERQC) components retain and degrade
      misfolded proteins, and our results have found that the degradation of the
      soluble ERQC substrates CPY* and PrA* but not membrane spanning ERQC substrates
      requires transport between the ER and Golgi. Stabilization of these misfolded
      soluble proteins was seen in cells lacking Erv29p, a probable Golgi localized
      protein that cycles through the ER by means of a di-lysine ER retrieval motif
      (KKKIY). Cells lacking Erv29p also displayed severely retarded ER exit kinetics
      for a subset of correctly folded proteins. We suggest that Erv29p is likely
      involved in cargo loading of a subset of proteins, including soluble misfolded
      proteins, into vesicles for ER exit. The stabilization of soluble ERQC substrates
      in both erv29Delta cells and sec mutants blocked in either ER exit (sec12) or
      vesicle delivery to the Golgi (sec18) suggests that ER-Golgi transport is
      required for ERQC and reveals a new aspect of the degradative mechanism.

PMID- 11316831
TI  - Cognitive functional status of age-confirmed centenarians in a population-based
      study.
AB  - The New England Centenarian Study is a population-based study of all centenarians
      in 8 towns near Boston, MA. Age was confirmed for 43 centenarians all alive on a
      designated date. To determine prevalence of dementia in centenarians, the authors
      analyzed neuropsychological, medical, and functional status data for 34 (79%) of
      the centenarians. Definition of dementia was based on the Consortium to Establish
      a Registry for Alzheimer's Disease criteria, and a Clinical Dementia Rating (CDR)
      score was formulated for each participant. Seven (21%) had no dementia (CDR score
      0), and an additional 4 (12%) were assigned a CDR score of 0.5, uncertain or
      deferred diagnosis. The remaining 22 (64%) had at least some degree of dementia.
      The authors calculated Barthel Index scores to determine ability to perform
      activities of daily living. There was a statistically significant correlation
      between CDR scores and Barthel Index scores (r = -0.73). Correlation was
      strongest for those with no or severe dementia, with the greatest range of
      function measured among those with moderate dementia.

PMID- 11316832
TI  - Cognitive functioning in centenarians: a coordinated analysis of results from
      three countries.
AB  - Cognitive functions among centenarians in Japan, Sweden, and the United States
      are described. Three areas are explored. First, definitions and prevalence of
      dementia are compared between Japan and SWEDEN: Second, levels of cognitive
      performances between centenarians and younger age groups are presented. Third,
      interindividual variations in cognitive performances in centenarians and younger
      persons are compared in Sweden and the United STATES: The Swedish and Japanese
      studies show a variation in prevalence of dementia between 40% and 63% with a
      relatively higher prevalence among women. Part of the variance is probably due to
      differences in sampling and criteria of dementia. Along with the lower cognitive
      performance in centenarians, compared with younger age groups, the Swedish and
      U.S. results show a wider range of performance among centenarians for those
      semantic or experientially related abilities that tend to be maintained over the
      adult life span. In contrast, a smaller range of performance is found for
      centenarians on those fluid or process-related abilities that have shown a
      downward age-related trajectory of performance. Lower variability is probably due
      to centenarians reaching the lower performance limit. The conclusions agree with
      the assumption of a general increase in cognitive differentiation with increasing
      age, primarily in measures of crystallized intelligence. The conclusions point to
      the general robustness of results across countries, as well as to the relative
      importance of cognition for longevity.

PMID- 11316833
TI  - Dementia is not inevitable: a population-based study of Danish centenarians.
AB  - The authors evaluated the prevalence of dementia in centenarians. In this
      population-based survey, persons living in Denmark who turned 100 during the
      period April 1, 1995--May 31, 1996 (N = 276) were interviewed and examined at
      their residences. Additional health information was retrieved from medical files,
      including the National Discharge Registry. A participation rate was 75%, and no
      differences were found between participants and nonparticipants regarding sex and
      type of housing. The prevalence of mild to severe dementia in centenarians was
      51%; 37% had no signs of dementia. Among the 105 demented centenarians, 13 (12%)
      had diseases (vitamin B12 and folic acid deficiencies, hypothyroidism,
      Parkinson's disease) that could contribute to a dementia diagnosis. Of the
      remaining 92 demented participants, 46 (50%) had 1 one or more cerebro- or
      cardiovascular diseases known to be risk factors in the development of dementia.
      The prevalence of these risk factors was the same in demented and nondemented
      participants, whereas hypertension was significantly more frequent in nondemented
      than demented participants. Dementia is common but not inevitable in
      centenarians. Cerebro- and cardiovascular diseases are equally common in demented
      and nondemented persons.

PMID- 11316834
TI  - The role of job-related rewards in retirement planning.
AB  - The authors used data from the first wave of the Health and Retirement Study ( F.
      Juster and R. Suzman 1995) to evaluate whether certain job-related gratifications
      might reduce retirement planning. Three definitions of retirement planning were
      evaluated and then regressed separately on a set of variables that included 3
      types of job-related satisfactions (intrinsic gratification, positive social
      relations, and ascendance in the workplace) and 7 covariates: education, age,
      sex, health, marital status, race, and pension eligibility. Findings indicated
      that jobs high in ascendance were related to an increase in certain types of
      retirement planning, but jobs high in intrinsic rewards and positive social
      relations were related to less planning, regardless of how planning was defined.
      The findings suggest that information about work-related rewards may be useful in
      targeting individuals who might benefit from retirement planning programs, in
      developing planning programs to help workers realize more complex retirement
      plans, and in assisting employers who hope to retain older workers.

PMID- 11316836
TI  - Gender differences in the relationship between marital status transitions and
      life satisfaction in later life.
AB  - This study examined life satisfaction among individuals who had undergone a
      transition in marital status and those whose marital status remained stable over
      a 7-year period. In particular, using data from a large-scale, longitudinal study
      we assessed life satisfaction as measured in 1983 and 1990 among 2,180 men and
      women between the ages of 67 and 102. Groups of individuals were identified on
      the basis of whether a spouse was present or absent at the two measurement
      points. This allowed for a classification of groups who experienced stability or
      transitions in marital status. Among those individuals whose marital status
      remained stable over the 7 years, women's life satisfaction declined and men's
      remained constant. Among those who experienced a transition--in particular, the
      loss of a spouse--a decline in life satisfaction was found for both men and
      women, decline being more predominant for men. In addition, men's life
      satisfaction increased over the 7-year period if they gained a spouse, whereas
      the same was not true for women. Generally, these findings imply that the
      relationship between marital status transitions or stability differs for men and
      women.

PMID- 11316835
TI  - Race and restless sleep complaint in older chronic dialysis patients and
      nondialysis community controls.
AB  - There is mixed evidence about the relation of race to risk of sleep disturbance.
      We explored the relation of race to restless sleep complaint in survey data from
      a cohort of 311 older patients undergoing chronic renal dialysis and a similarly
      aged cohort of 354 nondialysis controls. Older dialysis patients were
      significantly more likely to report restless sleep. Restless sleep complaint was
      related to comorbidity, depressed mood, use of sleep medications, and perceived
      health status in both groups. Black patients in the dialysis cohort had decreased
      odds of restless sleep, but Black and White controls did not differ significantly
      in reporting restless sleep. Compared with their more socially advantaged White
      counterparts, older Black dialysis patients may perceive the chronic dialysis
      care environment more favorably. The findings are consistent with the view that
      sleep quality in late life is likely to reflect a delicate balance between
      psychological as well as physical well-being.

PMID- 11316837
TI  - Measuring disability in nursing home residents: validity and reliability of a
      newly developed instrument.
AB  - A 24-item multidimensional nurse-administered Nursing Home Disabilities
      Instrument (NHDI) was developed to measure disabilities in nursing home
      residents. We present the psychometric features and value of this instrument,
      with the following domains assessed: Mobility, Activities of Daily Living (ADLs),
      Alertness, Resistance to Nursing Assistance, Incontinence, Cognition, and
      PERCEPTION: Test-retest and interrater reliability was assessed using the
      Spearman correlation coefficient. Internal consistency was examined by Cronbach's
      alpha. Criterion validity tests were performed by comparing the scales with
      scales of the Elderly Residents Rating Scale (BOP). Test-retest reliability
      correlation coefficients ranged from 0.63 to 0.94. Interrater reliability was
      high for the scales Cognition, Mobility, ADL, and Incontinence (0.79 to 0.93),
      moderate for Resistance (0.51), and low for Perception (0.33). Cronbach's alpha
      of the scales was high, ranging from 0.78 (Alertness) to 0.93 (Mobility); only
      Perception showed a low alpha: 0.54. Criterion validity was high for Cognition,
      ADL, and Mobility (0.75 to 0.78), and moderate for Alertness (0.59). The NHDI
      appears to be a valid and efficient multidimensional instrument for measuring
      disabilities in nursing home residents. These findings imply that the NHDI is a
      useful instrument for nursing homes to achieve a reliable assessment of
      cognitively impaired elders.

PMID- 11316838
TI  - The mediating effects of situational control on social support and mood following
      a stressor: a prospective study of dementia caregivers in their natural
      environments.
AB  - OBJECTIVES: The present study examined, prospectively and within the context of
      stress experienced in the natural environment, whether situational control served
      as a mediator between perceived social support and caregiver's mood. METHODS:
      Data came from baseline assessments of individuals participating in health
      promotion interventions for women caregivers. Participants were 49 female
      caregivers of dementia patients who monitored their own acute psychological
      states during the day. RESULTS: Results revealed that although the occurrence of
      a situational stressor increased negative mood, greater perceived support reduced
      the detrimental impact of a stressor on negative mood. Moreover, path analyses
      revealed that changes in situational control partially mediated the relationship
      between perceived support and stress-induced negative mood changes. However,
      changes in control did not serve as a mediator in analyses focused on happiness.
      DISCUSSION: Results suggest that caregivers with greater perceived support were
      less emotionally reactive to stress occurring in their natural environments
      because of, in part, sustained or increased situational control.

PMID- 11316839
TI  - A comparison of marital interaction patterns between couples in which the husband
      does or does not have Alzheimer's disease.
AB  - Objectives. Our main purpose was to examine similarities and differences in
      patterns of interpersonal interaction between Alzheimer's disease (AD) caregiving
      and noncaregiving couples (n = 54). Methods. Twenty-seven wives caring for
      moderately impaired husbands with probable AD and 27 noncaregiving wives from
      comparable sociodemographic backgrounds were videotaped in their homes during
      both mealtime and a future event planning task. In addition, they completed self
      report questionnaires to assess depression, stress, relationship mutuality, and
      perceived hope. Results. Compared with their counterparts, caregiving wives
      reported higher levels of depression and stress, but similar shared values and
      closeness. For the three factors developed from the Marital Interaction Coding
      System (MICS, version IV; Supportive Facilitative, and Rapport Building), a
      complex pattern of results was found in which disease status, type of task, and
      gender interacted significantly. Noncaregiving couples were more interactive
      overall and expressed more support to each other. Caregiving wives were found to
      be most facilitative during the planning task, whereas AD husbands were highest
      on interactions that built rapport (e.g., smiling) during that same task.
      Caregiving wives actually increased their facilitative behavior from the mealtime
      to planning task, probably reflecting the increased demand characteristics of the
      latter. DISCUSSION: This study is one of a small body of literature to describe
      the negative impact of AD on spousal communication as observed and coded in two
      videotaped interaction situations in the home. Suggestions are made for future
      research, including the inclusion of longitudinal designs and non-Caucasian
      couples.

PMID- 11316840
TI  - Aging, cohorts, and verbal ability.
AB  - OBJECTIVES: Age-related differences in cognitive abilities observed in cross
      sectional samples of individuals varying in age may in part be spurious due to
      the effects of cohort differences in schooling and related factors. This study
      examined the effects of aging on cognitive function controlling for any and all
      differences in cohort-based social experiences of different age groups. METHODS:
      We examined age-related patterns in a measure of verbal ability using 14 repeated
      cross-sectional surveys from the General Social Survey (GSS) over a 24-year
      period. RESULTS: The raw GSS data show the expected age-related growth and
      decline in vocabulary knowledge, but these age differences are reduced when
      adjusted for cohort differences. There is evidence of small age-related patterns
      in vocabulary knowledge within cohorts, but the curvilinear contributions of
      aging to variation in verbal scores account for less than one-third of 1% of the
      variance in vocabulary knowledge, once cohort is controlled. Cohort differences
      in schooling contribute substantially to this effect. DISCUSSION: Within-age
      group variation in vocabulary knowledge is vastly more important than age
      differences per se, and the complexities of the relationship of verbal skills to
      historical differences in the experience of schooling present an interesting
      avenue for future research.

PMID- 11316841
TI  - Eddies in the stream: the prevalence of uncertain plans for retirement.
AB  - OBJECTIVE: This study examined an assumption of retirement theory that typifies
      older workers as preretirees who are planfully engaged in paths toward
      retirement. METHODS: Using survey responses among workers in the 1992 and 1994
      waves of the Health and Retirement Study, we described the prevalence of
      nonsubstantive answers to questions about the expected form and timing of
      retirement (e.g., "don't know," "haven't thought about it"). We tested
      explanations for this uncertainty as an artifact of the survey process, but also
      as an outcome of the opportunity structure for retirement planning. RESULTS:
      Survey procedure did generate some of these noncommittal responses. Depending on
      question type, approximately 10% to 40% of workers did not state when or how they
      would retire, and such responses were less prevalent across age and time. In
      addition, categorical uncertainty about form and timing was theoretically
      predictable in a framework that supposed that workers less subject to a socially
      attended life--at work or away--would be more undecided about the future.
      DISCUSSION: Uncertainty is an authentic, meaningful stance toward retirement that
      theory and research design should not ignore. Just as actual transitions to
      retirement can be ambiguous or blurred, the expectation of retirement, as well,
      can be untidy.

PMID- 11316842
TI  - Age and sex differences in genetic and environmental factors for self-rated
      health: a twin study.
AB  - OBJECTIVES: Self-rated health has been shown to be a predictor for future health
      status and mortality. The purpose of this study was to investigate age-group and
      sex differences in genetic and environmental sources of variation for self-rated
      health. METHODS: A sample of twins from the Swedish Twin Registry participated in
      a computer-assisted telephone interview with assessment of self-rated health.
      Structural equation model analyses on 1,243 complete twin pairs provided
      estimates of genetic and environmental components of variance. RESULTS:
      Individual differences primarily reflected individual specific environmental
      influences at all ages. The increase in total variance across age groups was
      primarily due to genetic influences in the age groups 45--74 years and greater
      environmental influences in the oldest age group (>74). No significant sex
      differences were found in variance components. DISCUSSION: Genetic variance in
      the two middle age groups (45--74) could reflect genetic susceptibility to age
      dependent illnesses not yet expressed in the youngest group. The findings suggest
      that it might be more fruitful to explore the origins of individual differences
      for self-rated health in the context of an individual's age and birth cohort
      rather than in the context of sex.

PMID- 11316843
TI  - Disability as a function of social networks and support in elderly African
      Americans and Whites: the Duke EPESE 1986--1992.
AB  - OBJECTIVES: We examined the association of structural and functional aspects of
      social relationships with change in disability, and the degree to which race
      modifies these associations. METHODS: Data are from a population-based sample of
      4,136 African Americans and Whites aged > or = 65 living in North CAROLINA:
      Disability data were collected during seven consecutive yearly interviews and
      summarized in two outcome measures. Measures of social relationships included
      five measures representing network size, extent of social interaction, and
      specific type of relationships, as well as instrumental and emotional support.
      Weighted proportional odds models were fitted to model disability as a function
      of baseline social network and support variables, and the interaction of each
      variable with follow-up time. RESULTS: Network size and social interaction showed
      significant negative associations with disability risks, which did not vary by
      race, or as a function of time. Social interaction with friends was associated
      with a reduced risk for disability, but social interaction with children or
      relatives was not related to disability. Instrumental support was associated with
      a significantly increased disability risk, with a greater adverse effect among
      Whites than African AMERICANS: Emotional support was not associated with
      disability, but a protective effect for ADL disability was found after
      controlling for its intercorrelation with instrumental support. DISCUSSION: The
      findings provide further evidence for the role of social relationships in the
      disablement process, although not all types of social relationships may be
      equally beneficial. Furthermore, these associations may be more complex than
      simple causal effects. There were few racial differences in the association of
      social relationships with disability, with the possible exception of instrumental
      support, which may allude to possible sociocultural differences in the experience
      of instrumental support exchanges.

PMID- 11316845
TI  - Cisplatin decreases the abundance of aquaporin water channels in rat kidney.
AB  - The present study examined whether the cisplatin induced urinary concentration
      defect can be related to an altered regulation of aquaporin (AQP) water channels
      in the kidney. Cisplatin (8 mg/kg) was injected intraperitoneally into male
      Sprague-Dawley rats. The control group was without cisplatin treatment. Four d
      later, the expression of AQP1, AQP2, and AQP3 proteins was determined in the
      kidney. To specify further the primary point of derangement in the pathway that
      activates the arginine vasopressin-mediated AQP channels, different components of
      adenylyl cyclase complex were examined separately. The cisplatin treatment caused
      a polyuric renal failure in association with decreases of free water
      reabsorption. The expression of AQP1 and AQP2 was decreased in the cortex, the
      outer medulla, and the inner medulla, whereas that of AQP3 was decreased in the
      outer medulla and the inner medulla. The expression of AQP2 proteins in the
      apical membrane-enriched fraction decreased in parallel with that in the
      subapical vesicle-enriched fraction, indicating a preserved targeting.
      Immunohistochemistry of the outer medulla also revealed that cisplatin decreased
      immunoreactivity for AQP1, AQP2, and AQP3. The arginine vasopressin-evoked
      generation of cyclic adenosine monophosphate was attenuated by cisplatin, being
      most prominent in the outer medulla. However, the cyclic adenosine monophosphate
      generation in response to forskolin was not affected, whereas that to sodium
      fluoride was diminished significantly. Cisplatin also decreased the expression of
      Gsalpha proteins in the outer medulla and the inner medulla. These results
      suggest that a reduced expression of AQP water channels accounts at least in part
      for the cisplatin-induced urinary concentration defect.

PMID- 11316844
TI  - Role of renocortical cyclooxygenase-2 for renal vascular resistance and macula
      densa control of renin secretion.
AB  - This study aimed to assess the role of cyclooxygenase-2 (COX-2)-derived
      prostanoids for the macula densa control of renal afferent arteriolar resistance
      and for renin secretion. For this purpose, studied were the effects of blocking
      macula densa salt transport by the loop diuretic bumetanide (100 microM) on renal
      perfusate flow and on renin secretion in isolated perfused rats, in which
      renocortical COX-2 expression was prestimulated in vivo by treatment with the
      angiotensin-converting enzyme inhibitor ramipril, with low-salt diet, or with a
      combination of both. These maneuvers stimulated COX-2 expression in an order of
      ramipril + low salt>> low salt > ramipril > controls. Flow rates through isolated
      kidneys at a constant pressure of 100 mmHg were dependent on the pretreatment
      regimen, in the way that they went in parallel with COX-2 expression. The COX-2
      inhibitor NS-398 (10 microM) lowered flow rates depending on the COX-2 expression
      level and was most pronounced therefore after pretreatment with low salt +
      ramipril. NS-398 did not change the increase of flow in response to bumetanide
      but attenuated the stimulation of renin secretion in response to bumetanide in a
      manner depending on the expression level of COX-2. These findings suggest that in
      states of increased renocortical expression of COX-2, overall renal vascular
      resistance and the macula densa control of renin secretion become dependent on
      COX-2-derived prostanoids.

PMID- 11316846
TI  - Identification of a novel nuclear guanosine triphosphate-binding protein
      differentially expressed in renal disease.
AB  - A novel guanosine triphosphate-binding protein, chronic renal failure gene
      (CRFG), was discovered by differential display PCR to be regulated differentially
      in renal disease. Within the rat kidney, CRFG mRNA was localized to the outer
      medulla and was highly expressed in epithelial cells. The specific renal
      expression of CRFG mRNA in the outer medulla was reduced dramatically in several
      rat models of renal disease, including diabetic nephropathy, partial nephrectomy,
      ischemia, and anti-Thy1.1-induced nephritis. CRFG was localized selectively in
      the nucleus of human and rodent cells, as determined by immunocytochemistry and
      green fluorescence fusion protein. Cellular mRNA levels of CRFG were also
      increased after serum administration, when cells proliferate. These data suggest
      that CRFG may be involved in regulating guanosine triphosphate-dependent nuclear
      events that are associated with cell proliferation and that are important in
      normal renal function and essential for growth and development.

PMID- 11316847
TI  - Activated coagulation factor X: a novel mitogenic stimulus for human mesangial
      cells.
AB  - Intraglomerular activation of the coagulation cascade is a common feature of
      mesangioproliferative glomerulonephritis. Besides thrombin, very little is known
      about the cellular effects of other components of the coagulation system. This
      study investigated the effect of activated factor X (FXa) on cultured human
      mesangial cells. This serine protease induced a significant and dose-dependent
      increase in DNA synthesis. In addition to its mitogenic effect, FXa caused a
      striking upregulation of platelet-derived growth factor (PDGF) A and B chain gene
      expression. Next, the intracellular mitogenic signaling pathways activated by FXa
      were investigated. FXa induced a rapid spike in cytosolic calcium concentration
      followed by a sustained plateau. This response was not influenced by the
      downregulation of thrombin receptors. In addition, FXa stimulated a significant
      upregulation of different tyrosine-phosphorylated proteins. One of these
      phosphorylated cellular proteins was represented by the c-jun N-terminal kinase,
      a member of the mitogen-activated protein kinase family. To evaluate the role of
      FXa enzymatic activity and of PDGF autocrine secretion, FXa-induced DNA synthesis
      was studied in the presence of leupeptin, a specific serine protease inhibitor,
      and neutralizing anti-PDGF antibody. To investigate the role of tyrosine kinase
      (TK) activation on FXa mitogenic effect, FXa-stimulated thymidine uptake was
      evaluated in the presence of genistein and herbimycin A, two powerful and
      specific TK inhibitors. FXa-elicited DNA synthesis was also examined after
      protein kinase C (PKC) downregulation by prolonged incubation with phorbol-12
      myristate-13-acetate to study the influence of the phospholipase C-PKC axis. The
      proliferative effect of FXa required its proteolytic activity, and the activation
      of TK was only partially dependent on PKC activation while it was PDGF
      independent. Finally, it was shown by reverse transcription-PCR that mesangial
      cells do not express the signaling splicing variant of the putative FXa receptor,
      effector protease receptor-1. In conclusion, the present study demonstrated that
      FXa is a powerful mitogenic factor for human mesangial cells, and it induces its
      cellular effect not through effector protease receptor-1, but most likely by
      binding a protease-activated receptor and activating phospholipase C-PKC and TK
      signaling pathways.

PMID- 11316848
TI  - Role of the increase in p21 in cisplatin-induced acute renal failure in rats.
AB  - The goal of this study was to clarify the role of p21, a cyclin-dependent kinase
      inhibitor, in acute renal failure (ARF). This was accomplished with the
      examination of the renal expression of p21 in cisplatin (CDDP)-induced ARF and in
      rechallenge injury with CDDP. The injection of CDDP (5 mg/kg) into rats induced
      increases in serum creatinine and tubular damage and the number of in situ DNA
      nick end labeling-positive cells, which peaked at day 5, followed by recovery to
      control levels by day 14. The rechallenge with the same dose of CDDP 14 d after
      the first dose of CDDP induced significantly less injury and no significant
      increase in in situ DNA nick end labeling-positive cells. The first CDDP dose
      significantly increased p53-positive nuclei at day 1, which disappeared by day 5,
      and the number of p21-positive nuclei, which had two peaks on days 3 and 9. The
      number of proliferating cell nuclear antigen (PCNA)-positive nuclei peaked at
      days 3 and 12. A significant increase in the incorporation of 5-bromo 2'
      deoxyuridine (BrdU) was found at day 5 and peaked at day 7. The second injection
      of CDDP induced significant increases in the number of p21-, p53-, and PCNA
      positive nuclei within 2 d but did not affect the incorporation of BRDU: These
      findings suggested that (1) CDDP induced two peaks of the increase in p21; (2)
      the first peak occurred shortly after CDDP and was accompanied by overexpression
      of p53 and PCNA but not with BrdU incorporation, possibly reflecting G1 arrest
      and DNA repair; (3) the second peak of p21 occurred through an p53-independent
      pathway and may contribute to cell differentiation; and (4) the overexpression of
      p21 and PCNA in rechallenge injury may contribute to acquired resistance in CDDP
      induced ARF via enhanced DNA repair.

PMID- 11316849
TI  - Specific antagonism of PDGF prevents renal scarring in experimental
      glomerulonephritis.
AB  - Glomerular mesangial cell proliferation and/or mesangial matrix accumulation
      characterizes many progressive renal diseases. Rats with progressive
      mesangioproliferative glomerulonephritis were treated from day 3 to day 7 after
      disease induction with a high-affinity oligonucleotide aptamer antagonist against
      platelet-derived growth factor-B chain (PDGF-B). In comparison with nephritic
      rats that received vehicle or a scrambled aptamer, treatment with the PDGF-B
      aptamer led to a significant reduction of mesangioproliferative changes,
      glomerular hypertrophy, podocyte damage, and glomerular macrophage influx on day
      8. Both nephritic control groups subsequently developed progressive proteinuria
      and decreased renal function. On day 100, glomerulosclerosis, tubulointerstitial
      damage, glomerular and interstitial accumulation of types III and IV collagen,
      and overexpression of transforming growth factor-beta were widespread. All of
      these chronic changes were prevented in rats that received the PDGF-B aptamer,
      and their functional and morphologic parameters on day 100 were largely
      indistinguishable from non-nephritic rats. These data provide the first evidence
      for a causal role of PDGF in the pathogenesis of renal scarring and point to a
      new, highly effective therapeutic approach to progressive, in particular
      mesangioproliferative, renal disease.

PMID- 11316850
TI  - Chemokine and chemokine receptor expression during initiation and resolution of
      immune complex glomerulonephritis.
AB  - Chemokines participate in leukocyte infiltration, which plays a major role in
      glomerular injury during immune complex glomerulonephritis (IC-GN). Because
      target cell expression of chemokine receptors (CCR) is thought to mediate
      leukocyte migration, the expression pattern of chemokines and CCR in a model of
      IC-GN was examined. The transient course and predominant glomerular pathology of
      this model allows the examination of both the induction and resolution phases of
      IC-GN. GN was induced in mice by daily apoferritin injection for 2 wk. Urine
      samples and kidneys were obtained at 1, 2, and 4 wk. Albuminuria was noted at 2
      wk, but resolved after 4 wk. This was associated with glomerular IC deposits and
      mesangial proliferation. Glomerular macrophage infiltration was prominent at 1
      and 2 wk, which resolved at 4 wk. Expression of monocyte chemoattractant protein
      1 (MCP-1) and RANTES mRNA was upregulated at week 1 and decreased to control
      levels at weeks 2 and 4. The expression was localized to glomeruli by in situ
      hybridization and immunohistochemistry. The mRNA of CCR1, CCR2, and CCR5 but not
      CCR3 or CCR4 were upregulated at week 1 and decreased at weeks 2 and 4.
      Expression of CCR5 was located to the glomerulus by in situ hybridization and
      quantitative reverse transcription-PCR of isolated glomeruli. In summary, in a
      model of transient IC-GN, MCP-1 and RANTES and their receptors CCR1, CCR2, and
      CCR5 are expressed early and are already downregulated at the peak of proteinuria
      and leukocyte infiltration. Resolution of glomerulonephritis is associated with a
      return to baseline of chemokine and CCR expression. Therefore, it is concluded
      that glomerular MCP-1 and RANTES production directs circulating leukocytes that
      express CCR1, CCR2, and CCR5 into the glomerulus. After initiating GN, MCP-1 and
      RANTES and their receptors are readily downregulated.

PMID- 11316851
TI  - Proteinase 3 enhances endothelial monocyte chemoattractant protein-1 production
      and induces increased adhesion of neutrophils to endothelial cells by
      upregulating intercellular cell adhesion molecule-1.
AB  - Wegener's granulomatosis is an autoimmune disease that is characterized by
      systemic vasculitis and granuloma formation. Early influx of polymorphonuclear
      neutrophils (PMN), followed at a later stage by mononuclear cells, contributes to
      the granulomatous inflammation. Previous studies have shown that proteinase 3
      (PR3), the major autoantigen in Wegener's granulomatosis, specifically binds to
      endothelial cells and plays a possible role in activation of these cells by
      enhancing interleukin-8 production, thus providing a chemotactic and activating
      stimulus for PMN. The present study demonstrated that PR3 enhances the production
      of monocyte chemoattractant protein-1 (MCP-1) by human umbilical vein endothelial
      cells (HUVEC) in a dose- and time-dependent manner. The PR3-induced increase in
      MCP-1 production was demonstrated at both the protein and the mRNA levels and was
      chemotactic for monocytes. In addition, it was demonstrated that PR3 induces a
      dose- and time-dependent increase in the expression of intercellular adhesion
      molecule-1 (ICAM-1) as determined by fluorescence-activated cell sorter analysis.
      The PR3-induced increase in expression of ICAM-1 was also demonstrated at the
      mRNA level. PR3 induced a slight increase in vascular cell adhesion molecule-1
      expression and had no effect on the expression of both P- and E-selectin.
      Incubation of HUVEC for 24 h in the presence of PR3 resulted in a significant
      increase in adhesion of PMN, which was reduced to baseline levels in the presence
      of blocking monoclonal antibody anti-ICAM-1 or anti-CD18 or a combination of
      both. Monocytes showed a slight but statistically not significant increase in
      adhesion. Incubation of HUVEC with PR3 for 4 h did not result in enhanced
      adhesion of either PMN or monocytes. It was hypothesized that PR3, which may be
      released locally at inflammatory sites after activation of cytokine primed PMN,
      plays a role in endothelial cell activation by enhancing both interleukin-8 and
      MCP-1 production, thus providing a chemotactic and activating stimulus for both
      PMN and monocytes. In addition, PR3 may contribute to the ongoing inflammation by
      enhancing the adhesion of PMN to endothelial cells by upregulating ICAM-1
      expression.

PMID- 11316853
TI  - Electroporation-mediated gene transfer that targets glomeruli.
AB  - Electroporation has been applied to introducing DNA into several organs; however,
      gene expression was localized around the injected area. Examined was the
      efficiency of intrarenal injection of DNA followed by in vivo electroporation,
      using FITC-labeled oligodeoxynucleotides (FITC-ODN) and plasmid DNA expressing
      beta-galactosidase or luciferase. FITC-ODN or expression vectors were injected
      into the left renal artery; thereafter, the left kidney was electroporated
      between a pair of tweezer-type electrodes. FITC-ODN were transferred into all
      glomeruli, and transfected cells were identified as mesangial cells. Four d after
      transfection of the pCAGGS-LacZ gene, beta-galactosidase expression was observed
      in 75% of glomeruli. To compare the transfection efficacy by electroporation with
      that by the hemagglutinating virus of Japan (HVJ) liposome method, a luciferase
      reporter gene, pActLuc, was transferred into glomeruli by either electroporation
      or the HVJ liposome method. On day 4, electroporation resulted in higher
      glomerular luciferase activity than did the HVJ liposome method. We also observed
      that co-transfection of pcEBNA, an expression vector for Epstein-Barr virus
      nuclear antigen, and poriP-cLuc, oriP-harboring vector, resulted in an eightfold
      higher luciferase gene expression than simple poriP-cLUC: No histologic damages
      were seen in glomeruli or tubular epithelial cells. In conclusion, gene transfer
      into renal artery followed by electroporation was an effective and simple
      strategy for gene transfer that targets glomerular mesangial cells.

PMID- 11316852
TI  - Blocking angiotensin II synthesis/activity preserves glomerular nephrin in rats
      with severe nephrosis.
AB  - Angiotensin-converting enzyme inhibitors restore size-selective dysfunction of
      the glomerular barrier in experimental animals and humans with proteinuric
      nephropathies, although the structural and molecular determinants of such an
      effect are not completely understood. This study used an accelerated model of
      experimental nephrosis to assess nephrin gene and protein expression in the
      kidney and the possible modulating effect of drugs that block angiotensin II
      (AII) synthesis/activity. Passive Heymann nephritis (PHN) and control animals
      were studied at day 7, month 4, and month 8. Additional PHN rats were treated
      with lisinopril or AII receptor blocker L-158,809 and studied at 8 mo. Lisinopril
      and L-158,809 controlled BP, prevented proteinuria, and protected PHN animals
      from renal injury. An intense signal of nephrin mRNA was detected in glomeruli of
      control animals mainly restricted to podocytes. In PHN rats, nephrin staining
      progressively and remarkably decreased with time. Lisinopril and L-158,809 fully
      prevented the decrease in nephrin transcripts to levels comparable to those of
      control rats. Consistent with nephrin mRNA expression, immunostaining of the
      protein showed a progressive decrease in kidneys from PHN rats that was
      completely abolished by lisinopril and L-158,809. In summary, progressive renal
      injury was associated with downregulation of nephrin gene that was totally
      prevented by angiotensin-converting enzyme inhibitor and AII receptor blocker,
      suggesting that renoprotection afforded by drugs that interfere with AII
      synthesis/activity was related to an effect on nephrin assembly.

PMID- 11316854
TI  - Mutation analysis of the entire replicated portion of PKD1 using genomic DNA
      samples.
AB  - The replicated portion of PKD1, which comprises nearly 70% of the length of the
      gene, is predicted to harbor at least 85% of the mutations present in affected
      autosomal dominant polycystic kidney disease type 1 pedigrees. The relative
      paucity of reported mutations involving this segment is attributable to the
      significant technical challenges posed by the genomic structure of the gene.
      Previous genomic DNA-based strategies were unable to evaluate exons 1 and 22 and
      relied on the use of 10- to 13-kb PCR products. In this report, a set of six
      novel primer pair combinations, which can be used with previously reported
      reagents to analyze all of the exons in the replicated region (exons 1 to 34),
      are described. No product is greater than 5.8 kb in length, and various primer
      combinations can be used to reduce this length in half. Using this approach, two
      new pathogenic mutations, four novel disease-associated missense substitutions,
      and six new normal variants were identified. These new reagents should prove
      useful to investigators interested in performing DNA testing for this disorder.

PMID- 11316855
TI  - Induction of collecting duct morphogenesis in vitro by heparin-binding epidermal
      growth factor-like growth factor.
AB  - Heparin-binding epidermal growth factor-like growth factor (HB-EGF), a member of
      the epidermal growth factor family of growth factors, is synthesized as a
      membrane-an-chored precursor (proHB-EGF) that is capable of stimulating adjacent
      cells in a juxtacrine manner. ProHB-EGF is cleaved in a protein kinase C
      dependent process, to yield the soluble form. It was observed that HB-EGF acts as
      a morphogen for the collecting duct system in developing kidneys. HB-EGF protein
      was expressed in the ureteric bud of embryonic kidneys. Cultured mouse ureteric
      bud cells (UBC) produced HB-EGF via protein kinase C activation. After
      stimulation with phorbol ester (12-O-tetradecanoylphorbol-13-acetate) or
      recombinant soluble HB-EGF, UBC cultured in three-dimensional collagen gels
      formed short tubules with varied abundant branches. When proHB-EGF-transfected
      UBC were stimulated with 12-O-tetradecanoylphorbol-13-acetate and cultured in
      collagen gels, they exhibited linear growth, forming long tubular structures with
      few branches at the time of appearance of proHB-EGF on the cell surface. The
      structures exhibited a strong resemblance to the early branching ureteric bud of
      embryonic kidneys. When UBC were cultured in the presence of transforming growth
      factor-beta and soluble HB-EGF, they formed long tubules and few branches,
      similar to the structures observed in proHB-EGF-transfected UBC. These cells
      exhibited apical-basolateral polarization and expression of the water channel
      aquaporin-2. These findings indicate that soluble HB-EGF and proHB-EGF induce
      branching tubulogenesis in UBC in different ways. Juxtacrine activation by proHB
      EGF or the synergic action of soluble HB-EGF with transforming growth factor-beta
      is important for well balanced morphogenesis of the collecting duct system.

PMID- 11316856
TI  - De novo demonstration and co-localization of free-radical production and
      apoptosis formation in rat kidney subjected to ischemia/reperfusion.
AB  - Ischemia-induced oxidative damage to the reperfused kidney was examined. A
      modified chemiluminescence method, an in situ nitro blue tetrazolium perfusion
      technique, and a DNA fragmentation/apoptosis-related protein assay were adapted
      for demonstration de novo and co-localization of reactive oxygen species (ROS)
      production and apoptosis formation in rat kidneys subjected to
      ischemia/reperfusion injury. The results showed that prolonged ischemia
      potentiated proapoptotic mechanisms, including increases in the Bax/Bcl-2 ratio,
      CPP32 expression, and poly-(ADP-ribose)-polymerase fragments, and subsequently
      resulted in severe apoptosis, including increases in DNA fragmentation and
      apoptotic cell number in renal proximal tubules (PT) and distal tubules (DT) in a
      time-dependent manner. The increased level of ROS detected on the renal surface
      was correlated with that in blood and was intensified by a prolonged interval of
      ischemia. The main source of ROS synthesis was the PT epithelial cells. The ROS
      and apoptotic nuclei detected in the PT cells can be ameliorated by superoxide
      dismutase (SOD) treatment before reperfusion. However, the apoptotic nuclei
      remained in DT in the SOD-treated rats, indicating that formation of apoptosis in
      DT was not influenced by the small amounts of ROS produced. In PT and DT cell
      cultures, significant increases in apoptotic cells and ROS were evident in PT
      cells after hypoxia/reoxygenation insult. Furthermore, the oxidative damage in
      PT, but not in DT, can be alleviated by ROS scavengers SOD and
      hexa(sulfobutyl)fullerene, confirming that PT are vulnerable to ROS. These
      results lead us to conclude that ROS produced in significant amounts in PT
      epithelium under ischemia/reperfusion or hypoxia/reoxygenation conditions may be
      responsible for the apoptotic death of these cells.

PMID- 11316857
TI  - Role of p53-dependent activation of caspases in chronic obstructive uropathy:
      evidence from p53 null mutant mice.
AB  - Chronic obstructive uropathy (COU) created by unilateral ureteric ligation is
      associated with increased renal cell apoptosis and p53 expression. Genetically
      engineered mice were used to examine the role of p53 in renal cell apoptosis in
      COU and the involved molecular pathways. Obstructed kidneys in p53+/+, p53+/-,
      and p53-/- mice were examined at days 4, 7, 15, 20, and 30 for apoptosis, and
      mRNA were examined for p53, members of the bcl-2 family, the death receptor
      family, and the common effectors of apoptosis. Obstructed kidneys in p53+/- and
      p53-/- mice exhibited equal attenuation of tubular and interstitial cell
      apoptosis (70 and 50%, respectively), compared with p53+/+ mice. However, p53
      gene deficiency did not confer complete protection from apoptosis. Obstructed
      kidneys from p53-/- mice did not express p53 mRNA, whereas those from p53+/- and
      p53+/+ mice displayed mild and marked increase in their expression, respectively.
      Obstructed kidneys in p53+/+, p53+/-, and p53-/- mice displayed upregulation of
      mRNA for members of the bcl-2 family and most of the death receptor family,
      except for a lower level of tumor necrosis factor receptor-1, TRAIL, and FAP in
      p53+/+ mice. Obstructed kidneys in p53-/- and p53+/- mice showed virtual absence
      of caspase 11 and marked attenuation of caspases 1 and 12, contrasted with their
      strong expression in p53+/+ kidneys. These data suggest that apoptosis in
      obstructed kidneys involves p53-dependent as well as p53-independent pathways.
      The p53-dependent pathway may involve activation of caspases 1, 11, and 12,
      whereas the p53-independent pathway may involve activation of members of the bcl
      2 and death receptor families.

PMID- 11316858
TI  - Antibodies against vascular endothelial growth factor improve early renal
      dysfunction in experimental diabetes.
AB  - Vascular endothelial growth factor (VEGF) is a cytokine that potently stimulates
      angiogenesis, microvascular hyperpermeability, and endothelium-dependent
      vasodilation, effects that are largely mediated by endothelial nitric oxide
      synthase (eNOS). The expression of VEGF is pronounced in glomerular visceral
      epithelial cells, but its function in renal physiology and pathophysiology is
      unknown. VEGF expression is upregulated by high ambient glucose concentrations in
      several cell types in vitro and in glomeruli of diabetic rats. To assess the role
      of VEGF in the pathophysiology of early renal dysfunction in diabetes, monoclonal
      anti-VEGF antibodies (Ab) were administered to control and streptozotocin-induced
      diabetic rats for 6 wk after induction of diabetes. Based on in vitro binding
      studies, an adequate serum VEGF inhibitory activity was achieved during the
      entire course of anti-VEGF Ab administration. Anti-VEGF Ab treatment but not
      administration of isotype-matched control Ab decreased hyperfiltration,
      albuminuria, and glomerular hypertrophy in diabetic rats. VEGF blockade also
      prevented the upregulation of eNOS expression in glomerular capillary endothelial
      cells of diabetic rats. Antagonism of VEGF had no effect on GFR and glomerular
      volume in control rats. These results identify VEGF as a pathogenetic link
      between hyperglycemia and early renal dysfunction in diabetes. Targeting VEGF may
      prove useful as a therapeutic strategy for the treatment of early diabetic
      nephropathy.

PMID- 11316859
TI  - Diabetes insipidus in uricase-deficient mice: a model for evaluating therapy with
      poly(ethylene glycol)-modified uricase.
AB  - Uricase-deficient mice develop uric acid nephropathy, with high mortality rates
      before weaning. Urate excretion was quantitated and renal function was better
      defined in this study, to facilitate the use of these mice as a model for
      evaluating poly(ethylene glycol)-modified recombinant mammalian uricases (PEG
      uricase) as a potential therapy for gout and uric acid nephropathy. The uric
      acid/creatinine ratio in the urine of uricase-deficient mice ranges from 10 to
      >30; on a weight basis, these mice excrete 20- to 40-fold more urate than do
      human subjects. These mice consistently develop a severe defect in renal
      concentrating ability, resulting in an approximately sixfold greater urine volume
      and a fivefold greater fluid requirement, compared with normal mice. This
      nephrogenic diabetes insipidus leads to dehydration and death of nursing mice
      but, with adequate water replacement, high urine flow protects adults from
      progressive renal damage. Treatment of uricase-deficient mice with PEG-uricase
      markedly reduced urate levels and, when initiated before weaning, preserved the
      renal architecture (as evaluated by magnetic resonance micros-copy) and prevented
      the loss of renal concentrating function. PEG-uricase was far more effective and
      less immunogenic than unmodified uricase. Retention of uricase in most mammals
      and its loss in humans and some other primates may reflect the evolution of renal
      function under different environmental conditions. PEG-uricase could provide an
      effective therapy for uric acid nephropathy and refractory gout in human
      patients.

PMID- 11316860
TI  - Effects of albumin/furosemide mixtures on responses to furosemide in
      hypoalbuminemic patients.
AB  - Hypoalbuminemic patients often have sufficient fluid accumulation to mandate
      diuretic therapy but are often resistant to diuresis. Studies have suggested that
      hypoalbuminemia itself impairs delivery of effective amounts of diuretic agent
      into the urine, the site of action. Therefore, administration of mixtures of
      albumin and loop diuretics may enhance responses. Thirteen patients with biopsy
      proven cirrhosis and ascites (age, 51.2 +/- 8.1 yr; Child-Pugh score, 8.5 +/-
      1.0; serum albumin concentration, 3.0 +/- 0.6 g/dl) were studied in this
      randomized crossover study. Sodium balance was maintained throughout the study
      with a metabolic diet. All patients received spironolactone, but administration
      of all other diuretic agents was discontinued. Each patient received all of the
      following four treatments intravenously: (1) 40 mg of furosemide, (2) 25 g of
      albumin, (3) 40 mg of furosemide and 25 g of albumin premixed ex vivo, and (4) 40
      mg of furosemide and 25 g of albumin infused simultaneously into different arms.
      Responses were assessed by measuring urinary sodium excretion and relating the
      urinary furosemide excretion rate to the sodium excretion rate. Additionally, the
      pharmacokinetics of furosemide were assessed. Furosemide pharmacokinetics were
      similar for all treatment arms. Albumin alone had negligible diuretic effects.
      Neither albumin regimen increased the response to furosemide. Moreover, the
      relationship between the urinary furosemide excretion rate and the sodium
      excretion rate was unaffected by albumin. In conclusion, albumin failed to
      enhance the diuretic effects of furosemide in cirrhotic patients with ascites.
      Therefore, the coadministration of albumin and furosemide for the treatment of
      cirrhosis, and likely other hypoalbuminemic conditions, should not be used
      clinically.

PMID- 11316861
TI  - Transferrin synthesis is increased in nephrotic patients insufficiently to
      replace urinary losses.
AB  - The urinary loss of transferrin is sufficient to reduce plasma transferrin
      concentrations in the nephrotic syndrome. Hypotransferrinemia may lead to iron
      loss and microcytic anemia. The mechanism responsible for the hypotransferrinemia
      in the nephrotic syndrome is, however, unknown. In the present study, synthesis
      rate of transferrin was measured in vivo in nephrotic patients (n = 7) compared
      with control subjects (n = 6) using L-[1-(13)C]-valine. Plasma transferrin and
      iron concentration in the patients were significantly lower than in control
      subjects (transferrin, 1.39 +/- 0.08 versus 2.57 +/- 0.11 g/L, P < 0.0001; iron,
      10.2 +/- 0.8 versus 21.1 +/- 4.5 micromol/L, P = 0.02). Furthermore, albuminuria
      correlated with transferrinuria (r(2) = 0.901, P = 0.001). The absolute synthesis
      rate of transferrin was increased in the patients (10.0 +/- 1.1 versus 7.4 +/-
      0.7 mg/kg per d, P = 0.07), although this value failed to achieve significance. C
      reactive protein, plasma iron, and proteinuria did not correlate with transferrin
      synthesis. In contrast, transferrin synthesis correlated with albumin synthesis
      (r(2) = 0.648, P = 0.03; n = 7). The present study indicates that increased
      transferrin synthesis occurs in nephrotic patients but is insufficient to
      compensate for urinary losses. Because, overall, no significant relationship was
      found between transferrin synthesis and either C-reactive protein or iron, it is
      unlikely that inflammation suppresses or that iron deficiency stimulates
      increased transferrin synthesis in these patients. The correlation between
      transferrin synthesis and albumin synthesis suggests that transferrin synthesis
      is a component of a general response in hepatic protein synthesis in the
      nephrotic syndrome. This suggests that a therapeutic approach to maximize plasma
      transferrin concentrations in nephrotic patients should be aimed primarily at
      reducing urinary protein excretion.

PMID- 11316862
TI  - Toward proteomics in uroscopy: urinary protein profiles after radiocontrast
      medium administration.
AB  - Previous attempts to use urinary protein profiles for diagnostic purposes have
      been rather disappointing with respect to their clinical validity, in part
      because of the insufficient reproducibility, sensitivity, and rapidity of
      available techniques. Therefore, a newly developed, high-throughput technique,
      namely surface-enhanced laser desorption/ionization (SELDI) ProteinChip array
      time of flight mass spectrometry, was studied, to assess its applicability for
      protein profiling of urine and to exemplify its use for a group of patients
      receiving radiocontrast medium. Assessment of the accuracy, sensitivity, and
      reproducibility of SELDI in test urinary protein profiling was performed. Renal
      function was studied in 20 male Sprague-Dawley rats before and after intravenous
      administration of either 1.25 g/kg ioxilan (n = 10) or hypertonic saline solution
      (n = 10) as a control. Urine samples from 25 patients undergoing cardiac
      catheterization were obtained before, immediately after, and 6 to 12 h after the
      procedure. Administration of ioxilan to rats resulted in changes in the abundance
      of proteins of 9.9, 18.7, 21.0, and 66.3 kD. For patients, even in uncomplicated
      cases of radiocontrast medium infusion during cardiac catheterization,
      perturbations in the protein composition occurred but returned to baseline values
      after 6 to 12 h. Proteins with molecular masses of 9.75, 11.75, 23.5, and 66.4 kD
      changed in abundance. For patients with impaired renal function, these changes
      were not reversible within 6 to 12 h. As a proof of principle, one of the peaks,
      i.e., that at 11.75 kD, was identified as beta(2)-microglobulin. SELDI is a
      promising tool for the detection, identification, and characterization of trace
      amounts of proteins in urine. Even for patients without renal complications,
      proteins with a broad range of molecular masses either appear in or disappear
      from the urine. Some of these might represent markers of impending nephropathy.

PMID- 11316863
TI  - Expression of aquaporin-1 in human peritoneal mesothelial cells and its
      upregulation by glucose in vitro.
AB  - Aquaporin (AQP) is a family of water channels that are highly selective for the
      passage of water and occasionally glycerol. In previous studies, only AQP1 was
      found in human peritoneal endothelial cells in both control subjects and patients
      on peritoneal dialysis. As human peritoneal mesothelial cells (HPMC) play an
      important role in dialysis adequacy and fluid balance in continuous ambulatory
      peritoneal dialysis patients, this study examined whether AQP1 is present in
      HPMC. It was found that AQP1 mRNA and protein are present in HPMC constitutively.
      The localization of AQP1 protein in peritoneal mesothelial cells was confirmed by
      double immunohistochemical staining of the mesothelial lining of human peritoneal
      membrane. More important, the expression of AQP1 in HPMC is not constitutive and
      the transcription and biosynthesis of AQP1 in HPMC is inducible by osmotic agents
      such as glucose and mannitol. There was significant enhancement of AQP1
      biosynthesis upon exposure to glucose in a time- and dose-dependent manner (P <
      0.0001). Similar findings were observed in the AQP1 biosynthesis by an
      endothelial cell line, EA.hy 926. Of particular interest, the upregulation in
      AQP1 mRNA or biosynthesis in mesothelial cells was always significantly higher
      than that of endothelial cells when the experiments were conducted under
      identical settings (P < 0.001). AQP1 expression in HPMC was demonstrated for the
      first time. Osmotic agents upregulate both mRNA and protein expression of this
      aquaporin. The role of AQP1 in HPMC in maintaining the ultrafiltration of the
      peritoneal membrane is potentially of clinical interest.

PMID- 11316864
TI  - Peritoneal glucose exposure and changes in membrane solute transport with time on
      peritoneal dialysis.
AB  - Peritoneal solute transport increases with time on treatment in a proportion of
      peritoneal dialysis (PD) patients, contributing to ultrafiltration failure.
      Continuous exposure of the peritoneum to hypertonic glucose solutions results in
      morphologic damage that may have a causative role in changes in peritoneal
      function. The purpose of this analysis was to establish whether increased
      exposure to glucose preceded changes in solute transport in a selected group of
      long-term PD patients. Peritoneal solute transport, residual renal function,
      peritonitis rate, and peritoneal exposure to glucose were recorded prospectively
      in a cohort of 303 patients at a single dialysis center. A subgroup of
      individuals, treated continuously for 5 yr, were identified and defined
      retrospectively as having either stable or increasing transport status. Of the 22
      patients who were treated continuously for 5 yr, 13 had stable solute transport
      (solute transport at start, 0.67 [+/-0.1]; at 5 yr, 0.67 [+/-0.1]), whereas 9 had
      a sustained increase (solute transport at start, 0.56 [+/-0.08]; at 5 yr, 0.77
      [+/-0.09]). Compared with the stable patients, those with increasing transport
      had earlier loss in residual renal function and were exposed to significantly
      more hypertonic glucose during the first 2 yr of treatment that preceded the
      increase in solute transport. This was associated with greater achieved
      ultrafiltration compensating for the reduced urinary volumes in these patients.
      Further increases in glucose exposure were observed as solute transport continued
      to rise. Peritonitis, including severity of infection and causative organism, was
      similar in both groups. In this selected group of long-term survivors on PD, an
      increase in solute transport with time was preceded by increased peritoneal
      exposure to hypertonic glucose. This is supportive evidence that hypertonic
      glucose may play a causative role in alterations in peritoneal membrane function.

PMID- 11316865
TI  - Impact of apolipoprotein(a) phenotypes on long-term renal transplant survival.
AB  - The long-term success of renal transplantation is limited because of chronic
      rejection (CR), which shows histologic parallels to atherosclerosis.
      Lipoprotein(a) [Lp(a)] is an independent risk factor for atherosclerosis, but its
      role in CR has not been investigated. Plasma levels of Lp(a) are determined
      mainly by the inherited isoform (phenotype) of apolipoprotein(a) [apo(a)] and
      show an inverse correlation with the molecular weight of apo(a). Apo(a) isoforms
      were identified in frozen sera of 327 patients who received a renal transplant
      during 1982 to 1992. Long-term graft survival in recipients with high molecular
      weight (HMW) or low molecular weight (LMW) apo(a) phenotypes were compared
      retrospectively. Mean (95% confidence interval) transplant survival was 12.8 yr
      (range, 11.9 to 13.6 yr) in patients with HMW and 11.9 yr (range, 10.8 to 13.1
      yr) in patients with LMW apo(a) phenotypes (P = 0.2065). In patients who were 35
      yr or younger at the time of transplantation, mean transplant survival was more
      than 3 yr longer in recipients with HMW apo(a) phenotypes compared with those
      with LMW apo(a) phenotypes (13.2 yr [range, 12.1 to 14.4 yr] versus 9.9 yr
      (range, 8.5 to 11.5 yr); P = 0.0156). In a Cox's proportional hazards regression
      model, the presence of LMW phenotypes-but not gender, immunosuppression, or HLA
      mismatches-in young patients was associated with a statistically significant risk
      of CR (P = 0.0434). These retrospective data indicate that young renal transplant
      recipients with LMW apo(a) phenotypes have a significantly shorter long-term
      graft survival, regardless of the number of HLA mismatches, gender, or
      immunosuppressive treatment.

PMID- 11316866
TI  - Pharmacokinetic interactions augment toxicities of sirolimus/cyclosporine
      combinations.
AB  - This study correlated the dynamic effects of sirolimus (rapamycin; RAPA) and
      cyclosporine (CsA) alone versus in combination to produce renal dysfunction,
      myelosuppression, or hyperlipidemia, with their corresponding blood and tissue
      concentrations. After salt-depleted rats were treated with RAPA (0.4 to 6.4 mg/kg
      per d) and/or CsA (2.5 to 20.0 mg/kg per d) for 14 d, the GFR, lipid levels, bone
      marrow cellularity, and CsA/RAPA concentrations in whole blood versus liver or
      renal tissues were measured, and the median effect model was used to discern the
      type of drug interactions. Compared with vehicle controls (1.98 +/- 0.34 ml/min),
      GFR values were reduced only by large doses of drug monotherapy, namely RAPA (3.2
      mg/kg per d = 1.2 +/- 0.02 ml/min or 6.4 mg/kg per d = 1.3 +/- 0.2 ml/min; both P
      < 0.01) or CsA (10.0 mg/kg per d = 1.2 +/- 0.1 ml/min or 20.0 mg/kg per d = 0.8
      +/- 0.4 ml/min; both P < 0.01). In contrast, hosts that were treated with smaller
      doses of CsA/RAPA combinations showed more pronounced effects in reduction of GFR
      values: 2.5/0.4 mg/kg per d, modestly (1.5 +/- 0.5 ml/min; P < 0.01); 5.0/0.8
      mg/kg per d, moderately (0.23 +/- 0.01 ml/min; P < 0.001); and higher-dose
      groups, markedly. The exacerbation of renal dysfunction seemed to be due to a
      pharmacokinetic interaction of RAPA to greatly increase CsA concentrations in
      whole blood and, particularly, in kidney tissue. In contrast, the pharmacodynamic
      effects of CsA to potentiate two RAPA-mediated toxicities-myelosuppression and
      increased serum cholesterol/low-density lipoprotein cholesterol-occurred
      independently of pharmacokinetic interactions. RAPA aggravates CsA-induced renal
      dysfunction owing to a pharmacokinetic interaction, whereas CsA produces a
      pharmacodynamic effect that augments RAPA-induced myelosuppression and
      hyperlipidemia.

PMID- 11316867
TI  - DNA microarray analysis of complex biologic processes.
AB  - DNA microarrays, or gene chips, allow surveys of gene expression, (i.e., mRNA
      expression) in a highly parallel and comprehensive manner. The pattern of gene
      expression produced, known as the expression profile, depicts the subset of gene
      transcripts expressed in a cell or tissue. At its most fundamental level, the
      expression profile can address qualitatively which genes are expressed in disease
      states. However, with the aid of bioinformatics tools such as cluster analysis,
      self-organizing maps, and principle component analysis, more sophisticated
      questions can be answered. Microarrays can be used to characterize the functions
      of novel genes, identify genes in a biologic pathway, analyze genetic variation,
      and identify therapeutic drug targets. Moreover, the expression profile can be
      used as a tissue or disease "fingerprint." This review details the fabrication of
      arrays, data management tools, and applications of microarrays to the field of
      renal research and the future of clinical practice.

PMID- 11316868
TI  - Left ventricular hypertrophy in the renal patient.

PMID- 11316869
TI  - Properties of the Na+-H+ exchanger in renal microvillus membrane vesicles. 1980.

PMID- 11316870
TI  - Crystal structure of E. coli beta-carbonic anhydrase, an enzyme with an unusual
      pH-dependent activity.
AB  - Carbonic anhydrases fall into three distinct evolutionary and structural classes:
      alpha, beta, and gamma. The beta-class carbonic anhydrases (beta-CAs) are widely
      distributed among higher plants, simple eukaryotes, eubacteria, and archaea. We
      have determined the crystal structure of ECCA, a beta-CA from Escherichia coli,
      to a resolution of 2.0 A. In agreement with the structure of the beta-CA from the
      chloroplast of the red alga Porphyridium purpureum, the active-site zinc in ECCA
      is tetrahedrally coordinated by the side chains of four conserved residues. These
      results confirm the observation of a unique pattern of zinc ligation in at least
      some beta-CAS: The absence of a water molecule in the inner coordination sphere
      is inconsistent with known mechanisms of CA activity. ECCA activity is highly pH
      dependent in the physiological range, and its expression in yeast complements an
      oxygen-sensitive phenotype displayed by a beta-CA-deletion strain. The structural
      and biochemical characterizations of ECCA presented here and the comparisons with
      other beta-CA structures suggest that ECCA can adopt two distinct conformations
      displaying widely divergent catalytic rates.

PMID- 11316871
TI  - X-ray structure of a novel matrix metalloproteinase inhibitor complexed to
      stromelysin.
AB  - A new class of matrix metalloproteinase (MMP) inhibitors has been identified by
      screening a collection of compounds against stromelysin. The inhibitors, 2,4,6
      pyrimidine triones, have proven to be potent inhibitors of gelatinases A and B.
      An X-ray crystal structure of one representative compound bound to the catalytic
      domain of stromelysin shows that the compounds bind at the active site and ligand
      the active-site zinc. The pyrimidine triones mimic substrates in forming hydrogen
      bonds to key residues in the active site, and provide opportunities for placing
      appropriately chosen groups into the S1' specificity pocket of MMPS: A number of
      compounds have been synthesized and assayed against stromelysin, and the
      variations in potency are explained in terms of the binding mode revealed in the
      X-ray crystal structure.

PMID- 11316872
TI  - An extended hydrophobic core induces EF-hand swapping.
AB  - The structure of calbindin D(9k) with two substitutions was determined by X-ray
      crystallography at 1.8-A resolution. Unlike wild-type calbindin D(9k), which is a
      monomeric protein with two EF-hands, the structure of the mutated calbindin D(9k)
      reveals an intertwined dimer. In the dimer, two EF-hands of the monomers have
      exchanged places, and thus a 3D domain-swapped dimer has been formed. EF-hand I
      of molecule A is packed toward EF-hand II of molecule B and vice versa. The
      formation of a hydrophobic cluster, in a region linking the EF-hands, promotes
      the conversion of monomers to 3D domain-swapped dimers. We propose a mechanism by
      which domain swapping takes place via the apo form of calbindin D(9k). Once
      formed, the calbindin D(9k) dimers are remarkably stable, as with even larger
      misfolded aggregates like amyloids. Thus calbindin D(9k) dimers cannot be
      converted to monomers by dilution. However, heating can be used for conversion,
      indicating high energy barriers separating monomers from dimers.

PMID- 11316873
TI  - pH-induced conformational transitions of a molten-globule-like state of the
      inhibitory prodomain of furin: implications for zymogen activation.
AB  - The endoprotease furin, which belongs to the family of mammalian proprotein
      convertase (PC), is synthesized as a zymogen with an N-terminal, 81-residue
      inhibitory prodomain. It has been shown that the proenzyme form of furin
      undergoes a multistep 'autocatalytic' removal of the prodomain at the C-terminal
      side of the two consensus sites, R(78)-T-K-R(81) approximately and R(44)-G-V-T-K
      R(49) approximately. The furin-mediated cleavage at R(44)-G-V-T-K-R(49)
      approximately, in particular, is significantly accelerated in an 'acidic'
      environment. Here, we show that under neutral pH conditions, the inhibitory
      prodomain of furin is partially folded and undergoes conformational exchanges as
      indicated by extensive broadening of the NMR spectra. Presence of many ring
      current shifted methyl resonances suggests that the partially folded state of the
      prodomain may still possess a 'semirigid' protein core with specific packing
      interactions among amino acid side chains. Measurements of the hydrodynamic radii
      and compaction factors indicate that this partially folded state is significantly
      more compact than a random chain. The conformational stability of the prodomain
      appears to be pH sensitive, in that the prodomain undergoes an unfolding
      transition towards acidic conditions. Our NMR analyses establish that the acid
      induced unfolding is mainly experienced by the residues from the C-terminal half
      of the prodomain (residues R(44)-R(81)) that contains the two furin cleavage
      sites. A 38-residue peptide fragment derived from the entire pH-sensitive C
      terminal region (residues R(44)-R(81)) does not exhibit any exchange-induced line
      broadening and adopts flexible conformations. We propose that at neutral pH, the
      cleavage site R(44)-G-V-T-K-R(49) approximately is buried within the protein core
      that is formed in part by residues from the N-terminal region, and that the
      cleavage site becomes exposed under acidic conditions, leading to a facile
      cleavage by the furin enzyme.

PMID- 11316874
TI  - Observation of the closing of individual hydrogen bonds during TFE-induced helix
      formation in a peptide.
AB  - Helix formation of an S-peptide analog, comprising the first 20 residues of
      Ribonuclease A and two additional N-terminal residues, was studied by measuring
      hydrogen bond (H-bond) (h3)J(NC') scalar couplings as a function of 2,2,2
      trifluoroethanol (TFE) concentration. The (h3)J(NC') couplings give direct
      evidence for the closing of individual backbone N-H***O = C H-bonds during the
      TFE-induced formation of secondary structure. Whereas no (h3)J(NC') correlations
      could be detected without TFE, alpha-helical (i,i +4) H-bond correlations were
      observed for the amides of residues A5 to M15 in the presence of TFE. The
      analysis of individual coupling constants indicates that alpha-helix formation
      starts at the center of the S-peptide around residue E11 and proceeds gradually
      from there to both peptide ends as the TFE concentration is increased. At 60% to
      90% TFE, well-formed alpha-helical H-bonds were observed for the amides hydrogens
      of residues K9 to Q13, whereas H-bonds of residues T5 to A8, H14, and M15 are
      affected by fraying. No intramolecular backbone H-bonds are present at and beyond
      the putative helix stop signal D16. As the (h3)J(NC') constants represent
      ensemble averages and the dependence of (h3)J(NC') on H-bond lengths is very
      steep, the size of the individual (h3)J(NC') coupling constants can be used as a
      measure for the population of a closed H-bond. These individual populations are
      in agreement with results derived from the Lifson-Roig theory for coil-to-helix
      transitions. The present work shows that the closing of individual H-bonds during
      TFE-induced helix formation can be monitored by changes in the size of H-bond
      scalar couplings.

PMID- 11316875
TI  - High-resolution crystal structure of deoxy hemoglobin complexed with a potent
      allosteric effector.
AB  - The crystal structure of human deoxy hemoglobin (Hb) complexed with a potent
      allosteric effector (2-[4-[[(3,5-dimethylanilino)carbonyl]methyl]phenoxy]-2
      methylpropionic acid) = RSR-13) is reported at 1.85 A resolution. Analysis of the
      hemoglobin:effector complex indicates that two of these molecules bind to the
      central water cavity of deoxy Hb in a symmetrical fashion, and that each
      constrains the protein by engaging in hydrogen bonding and hydrophobic
      interactions with three of its four subunits. Interestingly, we also find that
      water-mediated interactions between the bound effectors and the protein make
      significant contributions to the overall binding. Physiologically, the
      interaction of RSR-13 with Hb results in increased oxygen delivery to peripheral
      tissues. Thus, this compound has potential therapeutic application in the
      treatment of hypoxia, ischemia, and trauma-related blood loss. Currently, RSR-13
      is in phase III clinical trials as a radiosensitizing agent in the treatment of
      brain tumors. A detailed structural analysis of this compound complexed with
      deoxy Hb has important implications for the rational design of future analogs.

PMID- 11316876
TI  - Proton and metal ion-dependent assembly of a model diiron protein.
AB  - DF1 is a small, idealized model for carboxylate-bridged diiron proteins. This
      protein was designed to form a dimeric four-helix bundle with a dimetal ion
      binding site near the center of the structure, and its crystal structure has
      confirmed that it adopts the intended conformation. However, the protein showed
      limited solubility in aqueous buffer, and access to its active site was blocked
      by two hydrophobic side chains. The sequence of DF1 has now been modified to
      provide a very soluble protein (DF2) that binds metal ions in a rapid and
      reversible manner. Furthermore, the DF2 protein shows significant ferroxidase
      activity, suggesting that its dimetal center is accessible to oxygen. The
      affinity of DF2 for various first-row divalent cations deviates from the Irving
      Willliams series, suggesting that its structure imparts significant geometric
      preferences on the metal ion-binding site. Furthermore, in the absence of metal
      ions, the protein folds into a dimer with concomitant binding of two protons. The
      uptake of two protons is expected if the structure of the apo-protein is similar
      to that of the crystal structure of dizinc DF1. Thus, this result suggests that
      the active site of DF2 is retained in the absence of metal ions.

PMID- 11316877
TI  - Thermal unfolding of ribonuclease A in phosphate at neutral pH: deviations from
      the two-state model.
AB  - The thermal denaturation of ribonuclease A (RNase A) in the presence of phosphate
      at neutral pH was studied by differential scanning calorimetry (DSC) and a
      combination of optical spectroscopic techniques to probe the existence of
      intermediate states. Fourier transform infrared (FTIR) spectra of the amide I'
      band and far-uv circular dichroism (CD) spectra were used to monitor changes in
      the secondary structure. Changes in the tertiary structure were monitored by near
      uv CD. Spectral bandshape changes with change in temperature were analyzed using
      factor analysis. The global unfolding curves obtained from DSC confirmed that
      structural changes occur in the molecule before the main thermal denaturation
      transition. The analysis of the far-uv CD and FTIR spectra showed that these
      lower temperature-induced modifications occur in the secondary structure. No
      pretransition changes in the tertiary structure (near-uv CD) were observed. The
      initial changes observed in far-uv CD were attributed to the fraying of the
      helical segments, which would explain the loss of spectral intensity with almost
      no modification of spectral bandshape. Separate analyses of different regions of
      the FTIR amide I' band indicate that, in addition to alpha-helix, part of the
      pretransitional change also occurs in the beta-strands.

PMID- 11316878
TI  - Constrained modeling of spin-labeled major coat protein mutants from M13
      bacteriophage in a phospholipid bilayer.
AB  - The family of three-dimensional molecular structures of the major coat protein
      from the M13 bacteriophage, which was determined in detergent micelles by NMR
      methods, has been analyzed by constrained geometry optimization in a phospholipid
      environment. A single-layer solvation shell of dioleoyl phosphatidylcholine
      lipids was built around the protein, after replacing single residues by cysteines
      with a covalently attached maleimide spin label. Both the residues substituted
      and the phospholipid were chosen for comparison with site-directed spin labeling
      EPR measurements of distance and local mobility made previously on membranous
      assemblies of the M13 coat protein purified from viable mutants. The main
      criteria for identifying promising candidate structures, out of the 300 single
      residue mutant models generated for the membranous state, were 1) lack of steric
      conflicts with the phospholipid bilayer, 2) good match of the positions of spin
      labeled residues along the membrane normal with EPR measurements, and 3) a good
      match between the sequence profiles of local rotational freedom and a structural
      restriction parameter for the spin-labeled residues obtained from the model. A
      single subclass of structure has been identified that best satisfies these
      criteria simultaneously. The model presented here is useful for the
      interpretation of future experimental data on membranous M13 coat protein
      systems. It is also a good starting point for full-scale molecular dynamics
      simulations and for the design of further site-specific spectroscopic
      experiments.

PMID- 11316879
TI  - Crystal structure of a deletion mutant of human thymidylate synthase Delta (7-29)
      and its ternary complex with Tomudex and dUMP.
AB  - The crystal structures of a deletion mutant of human thymidylate synthase (TS)
      and its ternary complex with dUMP and Tomudex have been determined at 2.0 A and
      2.5 A resolution, respectively. The mutant TS, which lacks 23 residues near the
      amino terminus, is as active as the wild-type enzyme. The ternary complex is
      observed in the open conformation, similar to that of the free enzyme and to that
      of the ternary complex of rat TS with the same ligands. This is in contrast to
      Escherichia coli TS, where the ternary complex with Tomudex and dUMP is observed
      in the closed conformation. While the ligands interact with each other in
      identical fashion regardless of the enzyme conformation, they are displaced by
      about 1.0 A away from the catalytic cysteine in the open conformation. As a
      result, the covalent bond between the catalytic cysteine sulfhydryl and the base
      of dUMP, which is the first step in the reaction mechanism of TS and is observed
      in all ternary complexes of the E. coli enzyme, is not formed. This displacement
      results from differences in the interactions between Tomudex and the protein that
      are caused by differences in the environment of the glutamyl tail of the Tomudex
      molecule. Despite the absence of the closed conformation, Tomudex inhibits human
      TS ten-fold more strongly than E. coli TS. These results suggest that formation
      of a covalent bond between the catalytic cysteine and the substrate dUMP is not
      required for effective inhibition of human TS by cofactor analogs and could have
      implications for drug design by eliminating this as a condition for lead
      compounds.

PMID- 11316880
TI  - Structural basis of pheromone binding to mouse major urinary protein (MUP-I).
AB  - The mouse major urinary proteins are pheromone-binding proteins that function as
      carriers of volatile effectors of mouse physiology and behavior. Crystal
      structures of recombinant mouse major urinary protein-I (MUP-I) complexed with
      the synthetic pheromones, 2-sec-butyl-4,5-dihydrothiazole and 6-hydroxy-6-methyl
      3-heptanone, have been determined at high resolution. The purification of MUP-I
      from mouse liver and a high-resolution structure of the natural isolate are also
      reported. These results show the binding of 6-hydroxy-6-methyl-3-heptanone to MUP
      I, unambiguously define ligand orientations for two pheromones within the MUP-I
      binding site, and suggest how different chemical classes of pheromones can be
      accommodated within the MUP-I beta-barrel.

PMID- 11316882
TI  - Mechanistic aspects of cyanogenesis from active-site mutant Ser80Ala of
      hydroxynitrile lyase from Manihot esculenta in complex with acetone cyanohydrin.
AB  - The structure and function of hydroxynitrile lyase from Manihot esculenta (MeHNL)
      have been analyzed by X-ray crystallography and site-directed mutagenesis. The
      crystal structure of the MeHNL-S80A mutant enzyme has been refined to an R-factor
      of 18.0% against diffraction data to 2.1-A resolution. The three-dimensional
      structure of the MeHNL-S80A-acetone cyanohydrin complex was determined at 2.2-A
      resolution and refined to an R-factor of 18.7%. Thr11 and Cys81 involved in
      substrate binding have been substituted by Ala in site-directed mutagenesis. The
      kinetic measurements of these mutant enzymes are presented. Combined with
      structural data, the results support a mechanism for cyanogenesis in which His236
      as a general base abstracts a proton from Ser80, thereby allowing proton transfer
      from the hydroxyl group of acetone cyanohydrin to Ser80. The His236 imidazolium
      cation then facilitates the leaving of the nitrile group by proton donating.

PMID- 11316881
TI  - Genomic-scale comparison of sequence- and structure-based methods of function
      prediction: does structure provide additional insight?
AB  - A function annotation method using the sequence-to-structure-to-function paradigm
      is applied to the identification of all disulfide oxidoreductases in the
      Saccharomyces cerevisiae genome. The method identifies 27 sequences as potential
      disulfide oxidoreductases. All previously known thioredoxins, glutaredoxins, and
      disulfide isomerases are correctly identified. Three of the 27 predictions are
      probable false-positives. Three novel predictions, which subsequently have been
      experimentally validated, are presented. Two additional novel predictions suggest
      a disulfide oxidoreductase regulatory mechanism for two subunits (OST3 and OST6)
      of the yeast oligosaccharyltransferase complex. Based on homology, this
      prediction can be extended to a potential tumor suppressor gene, N33, in humans,
      whose biochemical function was not previously known. Attempts to obtain a folded,
      active N33 construct to test the prediction were unsuccessful. The results show
      that structure prediction coupled with biochemically relevant structural motifs
      is a powerful method for the function annotation of genome sequences and can
      provide more detailed, robust predictions than function prediction methods that
      rely on sequence comparison alone.

PMID- 11316883
TI  - Frequencies of amino acid strings in globular protein sequences indicate
      suppression of blocks of consecutive hydrophobic residues.
AB  - Patterns of hydrophobic and hydrophilic residues play a major role in protein
      folding and function. Long, predominantly hydrophobic strings of 20-22 amino
      acids each are associated with transmembrane helices and have been used to
      identify such sequences. Much less attention has been paid to hydrophobic
      sequences within globular proteins. In prior work on computer simulations of the
      competition between on-pathway folding and off-pathway aggregate formation, we
      found that long sequences of consecutive hydrophobic residues promoted
      aggregation within the model, even controlling for overall hydrophobic content.
      We report here on an analysis of the frequencies of different lengths of
      contiguous blocks of hydrophobic residues in a database of amino acid sequences
      of proteins of known structure. Sequences of three or more consecutive
      hydrophobic residues are found to be significantly less common in actual globular
      proteins than would be predicted if residues were selected independently. The
      result may reflect selection against long blocks of hydrophobic residues within
      globular proteins relative to what would be expected if residue hydrophobicities
      were independent of those of nearby residues in the sequence.

PMID- 11316884
TI  - Thermodynamic propensities of amino acids in the native state ensemble:
      implications for fold recognition.
AB  - An amino acid sequence, in the context of the solvent environment, contains all
      of the thermodynamic information necessary to encode a three-dimensional protein
      structure. To investigate the relationship between an amino acid sequence and its
      corresponding protein fold, a database of thermodynamic stability information was
      assembled that spanned 2951 residues from 44 nonhomologous proteins. This
      information was obtained using the COREX algorithm, which computes an ensemble
      based description of the native state of a protein. It was observed that amino
      acid types partitioned unequally into high, medium, and low thermodynamic
      stability environments. Furthermore, these distributions were reproducible and
      were significantly different than those expected from random partitioning. To
      assess the structural importance of the distributions, simple fold-recognition
      experiments were performed based on a 3D-1D scoring matrix containing only COREX
      residue stability information. This procedure was able to recover amino acid
      sequences corresponding to correct target structures more effectively than
      scoring matrices derived from randomized data. High-scoring sequences were often
      aligned correctly with their corresponding target profiles, suggesting that
      calculated thermodynamic stability profiles have the potential to encode sequence
      information. As a control, identical fold-recognition experiments were performed
      on the same database of proteins using DSSP secondary structure information in
      the scoring matrix, instead of COREX residue stability information. The
      comparable performance of both approaches suggested that COREX residue stability
      information and secondary structure information could be of equivalent utility in
      more sophisticated fold-recognition techniques. The results of this work are a
      consequence of the idea that amino acid sequences fold not into single, rigidly
      stable structures but rather into thermodynamic ensembles best represented by a
      time-averaged structure.

PMID- 11316885
TI  - Effect of pH and salt bridges on structural assembly: molecular structures of the
      monomer and intertwined dimer of the Eps8 SH3 domain.
AB  - The SH3 domain of Eps8 was previously found to form an intertwined, domain
      swapped dimer. We report here a monomeric structure of the EPS8 SH3 domain
      obtained from crystals grown at low pH, as well as an improved domain-swapped
      dimer structure at 1.8 A resolution. In the domain-swapped dimer the asymmetric
      unit contains two "hybrid-monomers." In the low pH form there are two
      independently folded SH3 molecules per asymmetric unit. The formation of
      intermolecular salt bridges is thought to be the reason for the formation of the
      dimer. On the basis of the monomer SH3 structure, it is argued that Eps8 SH3
      should, in principle, bind to peptides containing a PxxP motif. Recently it was
      reported that Eps8 SH3 binds to a peptide with a PxxDY motif. Because the "SH3
      fold" is conserved, alternate binding sites may be possible for the PxxDY motif
      to bind. The strand exchange or domain swap occurs at the n-src loops because the
      n-src loops are flexible. The thermal b-factors also indicate the flexible nature
      of n-src loops and a possible handle for domain swap initiation. Despite the loop
      swapping, the typical SH3 fold in both forms is conserved structurally. The
      interface of the acidic form of SH3 is stabilized by a tetragonal network of
      water molecules above hydrophobic residues. The intertwined dimer interface is
      stabilized by hydrophobic and aromatic stacking interactions in the core and by
      hydrophilic interactions on the surface.

PMID- 11316886
TI  - Structural and dynamic characterization of an unfolded state of poplar apo
      plastocyanin formed under nondenaturing conditions.
AB  - Plastocyanin is a predominantly beta-sheet protein containing a type I copper
      center. The conformational ensemble of a denatured state of apo-plastocyanin
      formed in solution under conditions of low salt and neutral pH has been
      investigated by multidimensional heteronuclear NMR spectroscopy. Chemical shift
      assignments were obtained by using three-dimensional triple-resonance NMR
      experiments to trace through-bond heteronuclear connectivities along the backbone
      and side chains. The (3)J(HN,Halpha) coupling constants, (15)N-edited proton
      proton nuclear Overhauser effects (NOEs), and (15)N relaxation parameters were
      also measured for the purpose of structural and dynamic characterization. Most of
      the residues corresponding to beta-strands in the folded protein exhibit small
      upfield shifts of the (13)C(alpha) and (13)CO resonances relative to random coil
      values, suggesting a slight preference for backbone dihedral angles in the beta
      region of (phi,psi) space. This is further supported by the presence of strong
      sequential d(alphaN)(i, i + 1) NOEs throughout the sequence. The few d(NN)(i, i +
      1) proton NOEs that are observed are mostly in regions that form loops in the
      native plastocyanin structure. No medium or long-range NOEs were observed. A
      short sequence, between residues 59 and 63, was found to populate a nonnative
      helical conformation in the unfolded state, as indicated by the shift of the
      (13)C(alpha), (13)CO, and (1)H(alpha) resonances relative to random coil values
      and by the decreased values of the (3)J(HN,Halpha) coupling constants. The (15)N
      relaxation parameters indicate restriction of motions on a nanosecond timescale
      in this region. Intriguingly, this helical conformation is present in a sequence
      that is close to but not in the same location as the single short helix in the
      native folded protein. The results are consistent with earlier NMR studies of
      peptide fragments of plastocyanin and confirm that the regions of the sequence
      that form beta-strands in the native protein spontaneously populate the beta
      region of (phi,psi) space under folding conditions, even in the absence of
      stabilizing tertiary interactions. We conclude that the state of apo-plastocyanin
      present under nondenaturing conditions is a noncompact unfolded state with some
      evidence of nativelike and nonnative local structuring that may be initiation
      sites for folding of the protein.

PMID- 11316887
TI  - Structural and thermodynamic analysis of the binding of solvent at internal sites
      in T4 lysozyme.
AB  - To investigate the structural and thermodynamic basis of the binding of solvent
      at internal sites within proteins a number of mutations were constructed in T4
      lysozyme. Some of these were designed to introduce new solvent-binding sites.
      Others were intended to displace solvent from preexisting sites. In one case Val
      149 was replaced with alanine, serine, cysteine, threonine, isoleucine, and
      glycine. Crystallographic analysis shows that, with the exception of isoleucine,
      each of these substitutions results in the binding of solvent at a polar site
      that is sterically blocked in the wild-type enzyme. Mutations designed to perturb
      or displace a solvent molecule present in the native enzyme included the
      replacement of Thr-152 with alanine, serine, cysteine, valine, and isoleucine.
      Although the solvent molecule was moved in some cases by up to 1.7 A, in no case
      was it completely removed from the folded protein. The results suggest that
      hydrogen bonds from the protein to bound solvent are energy neutral. The binding
      of solvent to internal sites within proteins also appears to be energy neutral
      except insofar as the bound solvent may prevent a loss of energy due to potential
      hydrogen bonding groups that would otherwise be unsatisfied. The introduction of
      a solvent-binding site appears to require not only a cavity to accommodate the
      water molecule but also the presence of polar groups to help satisfy its hydrogen
      bonding potential. It may be easier to design a site to accommodate two or more
      water molecules rather than one as the solvent molecules can then hydrogen-bond
      to each other. For similar reasons it is often difficult to design a point
      mutation that will displace a single solvent molecule from the core of a protein.

PMID- 11316888
TI  - Amide hydrogen exchange shows that malate dehydrogenase is a folded monomer at pH
      5.
AB  - Although there is general agreement that native mitochondrial malate
      dehydrogenase (MDH) exists as a dimer at pH 7, its aggregation state at pH 5 is
      less certain. The present amide hydrogen exchange study was performed to
      determine whether MDH remains a dimer at pH 5. To detect pH-induced changes in
      solvent accessibility, MDH was exposed to D(2)O at pH 5 or 7, then fragmented
      with pepsin into peptides that were analyzed by mass spectrometry. Even after
      adjustments for the effect of pH on the intrinsic rate of hydrogen exchange,
      large increases in deuterium levels were found at pH 5 only in peptic fragments
      derived from the subunit binding surface of MDH. In parallel experiments,
      elevated deuterium levels were also found in the same regions of MDH monomer
      trapped inside a mutant form of the chaperonin GROEL: This selective increase in
      hydrogen exchange rates, which was attributed to increased solvent accessibility
      of these regions, provides new evidence that MDH is a monomer at pH 5.

PMID- 11316889
TI  - Transfusion medicine and spongiform encephalopathy.

PMID- 11316890
TI  - Blood services costs and charges.

PMID- 11316891
TI  - Extracellular Babesia microti parasites.

PMID- 11316892
TI  - Immunochemical determination of cellular prion protein in plasma from healthy
      subjects and patients with sporadic CJD or other neurologic diseases.
AB  - BACKGROUND: Creutzfeldt-Jakob disease is thought to be caused by conversion of
      cellular prion protein (PrP) from its soluble form (PrP(sen)) to a pathologic
      form (PrP(res)). The occurrence of a new variant of CJD has increased the demand
      for a rapid assay capable of detecting a theoretical risk of transmission of the
      disease by blood or plasma. STUDY DESIGN AND METHODS: A quantitative sandwich
      ELISA for routine screening was developed for analysis of PrP levels in plasma.
      The time-resolved dissociation-enhanced fluorescence technology allowed a
      detection limit in plasma samples of approximately 50 pg/mL. Levels of PrP(sen)
      were tested in plasma from 31 patients with CJD, from 11 patients with other
      neurodegenerative diseases, and from a control group of 200 healthy subjects.
      RESULTS: The assay recognized both PrP(sen) and pathologic PrP(res), but did not
      differentiate between the two isoforms. PrP(sen) levels were higher in plasma
      from both patient groups than in plasma from the control group: 27 of the 31
      (87%) CJD patients and all patients with other neurodegenerative diseases had
      higher levels than the highest concentration found in the control group. No
      correlation was found between age and PrP level. No signal could be detected in
      the CJD samples after protease K digestion, indicating that all detected PrP was
      protease-sensitive and therefore not pathologic. CONCLUSION: These data suggest
      that soluble PrP(sen) in plasma samples might be useful as a surrogate marker for
      a broad spectrum of neurologic diseases as well as for CJD.

PMID- 11316893
TI  - A direct relationship between the partitioning of the pathogenic prion protein
      and transmissible spongiform encephalopathy infectivity during the purification
      of plasma proteins.
AB  - BACKGROUND: Experimental evidence from rodent models indicates that blood can
      contain transmissible spongiform encephalopathy (TSE) infectivity, which suggests
      a potential risk for TSE transmission via proteins isolated from human plasma.
      Because methods that can reduce TSE infectivity typically are detrimental to
      protein function, infectivity must be removed to ensure the safety of these
      therapeutic proteins. Animal bioassays are conventionally used to detect
      infectivity, but the pathogenic form of the prion protein (PrP(Sc)) can serve as
      a marker for TSE infectivity. STUDY DESIGN AND METHODS: Seven plasma protein
      purification steps were performed after the plasma intermediates were spiked with
      TSE-infected material. Resulting fractions were analyzed for PrP(Sc) by using a
      Western blot assay and for TSE infectivity by using an animal bioassay. Western
      blots were quantitated by an endpoint dilution analysis, and infectivity titers
      were calculated by the Spearman-Karber method. RESULTS: PrP(Sc) partitioning
      paralleled TSE infectivity partitioning, regardless of the nature of the protein
      purification step. The detection ranges for PrP(Sc) and infectivity were 0 to 5.3
      log and 1.1 to 8.9 log median infectious dose per unit, respectively. Clearance
      of PrP(Sc) and infectivity ranged from 1.0 to 6.0 log. CONCLUSION: Purification
      steps for isolating therapeutic proteins from human plasma showed the removal of
      both PrP(Sc) and TSE infectivity. PrP(Sc) partitioning coincided with infectivity
      partitioning, which showed a close relationship between PrP(Sc) and TSE
      infectivity. By exploiting this association, the in vitro Western blot assay for
      PrP(Sc) was valuable for estimating the partitioning of TSE infectivity during
      plasma protein purification.

PMID- 11316894
TI  - Inactivation of parvovirus B19 in coagulation factor concentrates by UVC
      radiation: assessment by an in vitro infectivity assay using CFU-E derived from
      peripheral blood CD34+ cells.
AB  - BACKGROUND: Nonenveloped and thermostable viruses such as parvovirus B19 (B19)
      can be transmitted to patients who are receiving plasma-derived coagulation
      factor concentrates treated by the S/D method for inactivating enveloped viruses.
      Therefore, it is important to develop and validate new methods for the
      inactivation of nonenveloped viruses. STUDY DESIGN AND METHODS: Suspensions of
      B19 in coagulation factor concentrates (FVIII) were irradiated with UVC light.
      B19 infectivity was determined by an indirect immunofluorescence assay using CFU
      E, as a host cell, derived from peripheral blood CD34+ cells. The effects of
      catechins on B19 infectivity and on FVIII activity after UVC illumination were
      also examined. RESULTS: The indirect immunofluorescence assay estimated the B19
      infectivity of samples containing virus copies of 10(5) to 10(11) per 10 microL
      to be a median tissue culture-infectious dose of 10(0.3) to 10(5.4) per 10
      microL. B19 was inactivated by 3 log at 750 J per m(2) of UVC radiation and was
      undetectable after 1000 or 2000 J per m(2) of irradiation. However, FVIII
      activity decreased to 55 to 60 percent of pretreatment activity after 2000 J per
      m(2) of UVC radiation. This was inhibited in the presence of rutin or catechins.
      Epigallocatechin gallate could maintain FVIII activity at almost 100 percent of
      pretreatment activity after 2000 J per m(2) of UVC radiation, while B19
      infectivity was decreased to undetectable levels, which resulted in >3.9 log
      inactivation. CONCLUSION: UVC radiation in the presence of catechins, especially
      epigallocatechin gallate, appears to be an effective method of increasing the
      viral safety of FVIII concentrates without the loss of coagulation activity.

PMID- 11316895
TI  - Patients with neoplastic and nonneoplastic hematologic diseases acquire CTLA-4
      antibodies after blood transfusion.
AB  - BACKGROUND: The presence of antibodies to CTLA-4, a negative regulator of T-cell
      activation, was investigated in multiply transfused patients with malignant and
      non- malignant hematologic diseases. A previous study showed that, in multiply
      transfused patients, an immune response against nuclear matrix proteins can be
      induced by WBCs undergoing apoptosis during RBC unit storage. This study
      evaluated whether the same phenomenon could be involved in the induction of CTLA
      4 antibodies in the patients analyzed. STUDY DESIGN AND METHODS: Patient sera
      were tested for binding to the recombinant full-length CTLA-4 beta-galactosidase
      fusion protein by an ELISA. Immuno-fluorescence stainings were performed to
      analyze the CTLA-4 epitopes recognized by the antibodies and to detect such
      epitopes in the apoptotic cells present in the RBC units. RESULTS: CTLA-4
      antibodies were found in multiply transfused patients with beta-thalassemia (40%)
      and with other hemolytic diseases (33%) including leukemias (42%). A higher
      incidence of CTLA-4 antibodies was found in patients receiving non-WBC-reduced
      blood (88%) than in those receiving WBC-reduced blood (26%). Immunofluorescence
      staining showed that WBCs undergoing apoptosis in the RBC unit expressed CTLA-4
      epitopes. CONCLUSIONS: The apoptotic WBCs present in the RBC units, after cold
      storage, express CTLA-4 epitopes. These epitopes can be released and induce
      formation of CTLA-4 antibodies with profound implications in the development of
      autoimmune disorders and in facilitating tumor dissemination and metastasis.

PMID- 11316896
TI  - Immune response to autologous transfusion in healthy volunteers: WB versus packed
      RBCs and FFP.
AB  - BACKGROUND: Storage of blood as packed RBCs and FFP is standard practice in
      allogeneic transfusion. Separation into components has been proposed for
      autologous transfusion, as well, but beneficial effects have not yet been shown.
      STUDY DESIGN AND METHODS: Twenty-four healthy male volunteers were randomly
      assigned to receive 1 unit of either autologous RBCs and FFP (RCP group) or WB
      (WB group) after 49 or 35 days of storage, respectively. The immune response was
      analyzed by ELISA for IL-6, C3a, terminal complement complex SC5b-9, TNF-alpha,
      and neopterin. Differential WBC counts and the phagocytosis of neutrophils and
      monocytes were measured by flow cytometry. RESULTS: Cell counts of monocytes
      (0.85 x 10(3) ng/microL) [corrected] and neutrophils (6.9 x 10(3) ng/microL)
      [corrected] increased 30 minutes after WB transfusion and then returned to close
      to the baseline values seen in the RCP group (0.47 and 2.9 x 10(3) ng/microL
      [corrected], respectively) throughout the monitored period (p<0.05). C3a (169 vs.
      116 ng/microL) [corrected] and IL-6 (29 vs. 6 pg/mL) reached higher plasma
      concentrations in the WB group (n = 11) than in the RCP group (n = 10).
      Phagocytosis of opsonized Escherichia coli was increased in neutrophils and
      monocytes and lasted up to 7 days after the transfusion of whole blood.
      CONCLUSION: Autologous WB induces a modest immunomodulation, but this effect is
      not observed upon transfusion of autologous blood components.

PMID- 11316897
TI  - Evaluation of an automated culture system for detecting bacterial contamination
      of platelets: an analysis with 15 contaminating organisms.
AB  - BACKGROUND: Approximately 1 in 2000 platelet components are bacterially
      contaminated. The time to detection of 15 seeded organisms in platelets recovered
      from an automated culture system was studied. STUDY DESIGN AND METHODS: Isolates
      of Bacillus cereus, Bacillus subtilis, Candida albicans, Clostridium perfringens,
      Corynebacterium species, Enterobacter cloacae, Escherichia coli, Klebsiella
      oxytoca, Propionibacterium acnes, Pseudomonas aeruginosa, Staphylococcus aureus,
      Staphylococcus epidermidis, Serratia marcescens, Streptococcus pyogenes, and
      Streptococcus viridans were inoculated into Day 2 apheresis platelet components
      to obtain a final concentration of approximately 10 and 100 CFU per mL (2
      units/organism). Each bag was sampled 10 times (20 mL/sample). Four mL of each
      sample was inoculated into standard aerobic and anaerobic bottles and into
      aerobic and anaerobic bottles containing charcoal; 2 mL was inoculated into
      pediatric aerobic bottles (so as to maintain a 1:10 ratio of sample to media) and
      1 mL into thioglycollate broth. RESULTS: With the exception of P. acnes, all
      organisms were detected in a mean of 9.2 to 25.6 hours. A range of 10 serial
      dilutions in inoculating concentrations was associated with an overall 10.1
      percent difference in detection time. A mean of 74.4 and 86.2 hours (100 and 10
      CFU/mL inocula, respectively) was required for the detection of P. acnes in
      anaerobic bottles. CONCLUSION: Bacteria thought to be clinically significant
      platelet contaminants can be detected in 9.2 to 25.6 hours when the starting
      concentration is approximately 10 to 100 CFU per mL. P. acnes required
      considerably longer incubation times for detection (in either aerobic or
      anaerobic bottles). However, P. acnes is of questionable clinical significance.
      Such a detection system could be used in either a blood collection center or a
      transfusion service to screen platelet concentrates for bacterial contamination.
      Such testing (with sterile sampling performed so as to maintain a closed-bag
      system) would be expected to save lives and might allow an extension of platelet
      storage.

PMID- 11316898
TI  - Automation of nucleic acid extraction for NAT screening of individual blood
      units.
AB  - BACKGROUND: Automation of NAT for single units of blood is currently hampered by
      the labor-intensive steps involved in the extraction of nucleic acids from
      samples before the amplification procedures. A new method has been developed for
      the automation of these steps using hydrophilic polyvinylidene fluoride (PVDF)
      filter plates. STUDY DESIGN AND METHODS: Quantitative nucleic acid recoveries
      from sera containing HCV, HIV, HBV, HAV, and human parvovirus B19 and from 3H
      labeled HCV RNA were determined in parallel by the semi-automated PVDF method and
      a single-column method (Qiagen). Quantitative PCR was performed. RESULTS: Similar
      recoveries of HCV, HIV, and HBV (with silica beads) were observed with the PVDF
      method and with the Qiagen single-column method. The sensitivity of the PVDF
      based PCR assay for HCV, HIV, and HBV in serially diluted serum samples was
      always within two serial dilutions of that obtained when the Qiagen single-column
      method was used in the same assays. With the use of 3H-labeled HCV RNA,
      recoveries of approximately 70 percent were found by both methods. CONCLUSION:
      The PVDF method will permit full automation of the simultaneous extraction of
      nucleic acid from sera containing HCV, HIV, and HBV. This procedure will permit
      NAT screening of individual units of blood, will replace the current screening of
      pools, and will achieve improved blood safety with reduced labor and costs.

PMID- 11316899
TI  - Autoimmune hemolytic anemia caused by IgG lambda-monotypic cold agglutinins of
      anti-Pr specificity after rubella infection.
AB  - BACKGROUND: In postinfection cold agglutinin (CA) disease, a relation between CA
      specificity and the underlying infectious agent has been observed. The induction
      of anti-I by Mycoplasma pneumoniae and that of anti-i by EBV are well-established
      examples. CASE REPORT: A 5-year-old boy developed severe hemolytic anemia after
      serologically ascertained rubella infection. Hemolysis was caused by high-titer
      CAs, which were analyzed by absorption and elution with sialidase-treated RBCs
      and hemagglutination-inhibition experiments. RESULTS: After elimination of normal
      anti-I and anti-T, the predominant CA was found to be an IgG lambda autoantibody
      with anti-Pr(1) specificity. CONCLUSION: This case seems to be of interest
      because it is the first report of severe CA-induced hemolysis after rubella
      infection, it is the first description of an IgG lambda-monotypic CA, and, along
      with previous case reports (three established and three suspected cases), it
      indicates a relationship between rubella infection and the CA specificity anti
      PR:

PMID- 11316900
TI  - Flow cytometric determination of RBC survival in autoimmune hemolytic anemia.
AB  - BACKGROUND: In cases of warm autoimmune hemolytic anemia (WAIHA), crossmatch
      incompatible RBCs are most often used for transfusion. The determination of the
      in vivo survival of transfused and autologous RBCs in WAIHA is helpful in the
      assessment of the efficacy of transfusion and other therapeutic interventions.
      CASE REPORT: A 38-year-old man presented with acute WAIHA, thrombocytopenia, and
      neutropenia. Steroids and IVIG therapy were ineffective, and the patient received
      RBCS: Because of increasing hemolysis and persisting thrombocytopenia,
      splenectomy was performed, resulting in partial remission. Further improvement
      was achieved by immunosuppressive therapy. MATERIALS AND METHODS AND RESULTS:
      Survival of transfused and autologous RBCs was determined, using a flow
      cytometric method based on the determination of different blood group antigens of
      patient and donor RBCS: The survival of autologous and transfused RBCs before
      splenectomy was determined on two consecutive days. The life span of autologous
      RBCs remained rather stable at 69 and 64 hours on Days 10 and 11, respectively,
      whereas the life span of transfused RBCs decreased from 186 hours to 25 hours.
      After splenectomy, the life span of transfused RBCs almost normalized: 43 days at
      postsplenectomy Day 3 and 87 days at postsplenectomy Day 69. CONCLUSION: Flow
      cytometry was successfully used to determine changing hemolytic activity during
      the clinical course of WAIHA. Additionally, the survival of transfused RBCs could
      be measured, which may be helpful to judge for the compatibility of allogeneic
      RBCS: Thus, we were able to show the therapeutic inefficacy of steroids and
      immunoglobulins, and quick improvement after splenectomy.

PMID- 11316901
TI  - Detection of fetal HPCs in maternal circulation after delivery.
AB  - BACKGROUND: Circulation of mature fetal blood cells in the maternal blood for a
      certain postpartum period has been verified, but detailed study of the fetal HPCs
      has not been reported. The objective of this study was to evaluate the frequency
      and clearance of these cells in the peripheral blood of puerperal women. STUDY
      DESIGN AND METHODS: PBMNCs from 15 puerperal women who gave birth to male infants
      were cultured in semi-solid medium containing hematopoietic stimulating factors.
      Colonies formed in the medium were individually characterized, collected, and
      subjected to PCR amplification of the SRY gene on Y chromosome to confirm fetal
      origin. RESULTS: The mean numbers of fetal progenitor cell colonies isolated per
      mL of maternal blood were 1.63, 2.48, 0.56, 0.12, and 0 on the day of delivery,
      at 4 days, 1 month, 6 months, and 1 year after delivery, respectively. There was
      no difference in the ratio of fetal versus maternal colonies between erythroid
      and granulocyte/macrophage lineages. CONCLUSION: The present study demonstrated
      that a significant number of fetal HPCs circulate in the maternal blood for a
      duration of at least 6 months after delivery.

PMID- 11316902
TI  - Human platelets express gangliosides with LKE activity and ABH blood group
      activity.
AB  - BACKGROUND: Platelets express several neutral glycosphingolipids with ABH and P
      blood group activity that may play a role in infectious, autoimmune, and
      alloimmune thrombocytopenia. In RBCs, sialylated glycosphingolipids or
      gangliosides with blood group activity have also been reported. To determine
      whether similar antigens are expressed by platelets, the total platelet
      ganglioside fraction was isolated and screened for blood-group-active
      glycosphingolipids. STUDY DESIGN AND METHODS: Platelet gangliosides were isolated
      by organic extraction, base hydrolysis, anion exchange, silicic acid, and high
      performance liquid chromatography. Gangliosides were identified and characterized
      by high-performance thin-layer chromatography-immunostaining with blood group
      specific MoAbs and glycosidase digestion. RESULTS: Group A, but not group O,
      platelets express five gangliosides with group A activity. Of five A MoAbs and
      lectins examined, only MoAbs Birma-1 and MHO4 recognized all five sialyl A bands.
      The sialyl A bands were sensitive to endoglycoceramidase and neuraminidase. One
      sialyl A band may represent a branched ganglioside with sialyl-I and group A
      activity. Platelets also express an LKE-active ganglioside consistent with sialyl
      galactosylgloboside. CONCLUSION: In addition to sialyl-iI and sialyl-Le(x)
      gangliosides, group A platelets express gangliosides with LKE activity and group
      A activity. Like RBCs, group A-active gangliosides may act as alloantigens and
      autoantigens to naturally occurring isohemagglutinins.

PMID- 11316903
TI  - Analysis of the kinetics of TPO uptake during platelet transfusion.
AB  - BACKGROUND: It has been shown in several studies that platelets play a role in
      the removal of TPO from the circulation. For instance, in vitro studies have
      shown that platelets can bind and internalize TPO, and transfusion studies have
      shown that the concentration of circulating TPO decreased after platelet
      transfusion. In the current study, the in vivo kinetics of plasma TPO levels and
      TPO uptake by transfused platelets is analyzed in more detail. STUDY DESIGN AND
      METHODS: Serial blood samples from patients who received a platelet transfusion
      were analyzed with respect to platelet count, plasma TPO concentration, and TPO
      content per platelet. In addition, the capacity of transfused platelets to bind
      TPO in vitro was assessed. RESULTS: Platelet counts increased immediately after
      transfusion, but subsequently started to decrease. Conversely, TPO levels
      decreased significantly but then returned to baseline level by 44 hours after
      transfusion. Platelet count and plasma TPO concentration were inversely
      correlated (r(p) = -0.9; p<0.05). The decrease in TPO concentration upon
      transfusion was accompanied by a significant increase in the platelet-associated
      TPO concentration. After transfusion, platelets isolated from the patient still
      displayed functional TPO receptors, as indicated by their intact capacity to bind
      TPO in vitro. CONCLUSION: The decrease in plasma TPO followed by the increase in
      platelet TPO provides evidence that platelets are responsible for the clearance
      of TPO in circulation. In vivo, platelets can bind and may degrade TPO upon
      platelet transfusion.

PMID- 11316904
TI  - Blood transfusion costs by diagnosis-related groups in 60 university hospitals in
      1995.
AB  - BACKGROUND: Transfusion services are frequently challenged to initiate efforts to
      reduce blood transfusion costs. One approach is to analyze blood transfusion
      costs for individual medical and surgical Diagnosis-Related Groups (DRGs). Rank
      ordering of DRGs by transfusion costs and interinstitutional comparisons of these
      costs may lead to the selection of DRGs for further analysis of the process of
      blood transfusion. STUDY DESIGN AND METHODS: Common DRGs (n = 486) that were
      related to discharges in 1995 were analyzed from 60 university hospital members
      of the University HealthSystems Consortium (UHC). Cost data were tabulated by
      using cost-to-charge ratios reflecting all aspects of blood transfusion-related
      costs of participating institutions. RESULTS: Of these 486 DRGs, 471 had
      identifiable mean blood costs, and 34 had median blood costs, mostly for surgical
      conditions. Transfusion costs represented a small proportion (< or = 1%) of total
      hospitalization costs for most DRGS: Nonetheless, millions of dollars were spent
      on blood transfusion, and for the most expensive DRGs, the costs ranged from 5.0
      to 8.6 percent of total hospitalization costs. Transfusion costs are more
      variable for the DRGs with the lowest transfusion costs than for those with the
      highest transfusion costs. CONCLUSION: Members of the UHC may utilize such
      analyses to identify surgical or medical diagnoses with transfusion costs at
      variance with the group norm. These DRGs could then be targeted for further
      evaluation of components contributing to high costs, for possible alterations in
      physician or clinical laboratory practices. Considering those conditions with the
      highest cumulative transfusion costs (e.g., BMT, liver transplant, acute
      leukemia, and cardiothoracic procedures), changes in transfusion practices that
      affect these particular patient categories may have a significant impact on
      global blood transfusion costs.

PMID- 11316905
TI  - Validating billing data for RBC transfusions: a brief report.
AB  - BACKGROUND: Administrative data are used often for research, but without
      validation of their accuracy. The validity of the billing for blood transfusion
      was assessed in one tertiary-care hospital. MATERIALS AND METHODS: Patient
      discharge data were retrieved from a database containing demographics, diagnoses,
      and charges. There was random selection of 358 patients who were billed for RBC
      transfusion and 358 who were not, within a 2-month period. The blood bank's
      transfusion records were reviewed. Sensitivity was defined as the proportion of
      transfused patients who were billed, and specificity as the proportion of
      nontransfused patients who were not billed. Patient characteristics were compared
      by using Wilcoxon's rank sum test and the chi-square test. RESULTS: Sixty-one
      transfused patients were not billed for the transfusion. No patient was billed
      without transfusion. Thus, the sensitivity and specificity were 83 percent (95%
      CI, 79-87%) and 100 percent, respectively. Nine patients who were not issued RBCs
      were appropriately not billed for RBCs, although the billing record suggests they
      had a procedure involving transfusion. These patients were called true-negative.
      The patients not billed were older (58 years vs. 55 years; p = 0.046) and less
      likely to have commercial insurance (5% vs. 15%; p = 0.035) than billed patients.
      CONCLUSIONS: The billing for RBC transfusion in one large institution is
      reassuringly valid. The specificity is excellent, and the sensitivity is higher
      than that seen in other studies of coding validity.

PMID- 11316906
TI  - Evaluation of a whole-blood WBC-reduction filter that saves platelets: in vitro
      studies.
AB  - BACKGROUND: In this study, a new WBC-reduction in-line filter that removes WBCs
      but not platelets was evaluated. Three WBC-reduced blood components were
      prepared: RBCs, plasma, and platelet concentrates (PCs). STUDY DESIGN AND
      METHODS: Whole-blood components (n = 30) were filtered within 2 to 4 hours after
      collection and then were centrifuged and separated into RBCs, plasma, and WBC
      reduced buffy coat. Saline-adenine-glucose-mannitol solution was added to the
      RBCS: The WBC-reduced buffy coats were stored overnight; on the following day,
      PCs were prepared from pooled WBC-reduced buffy coats and stored in a medium
      composed of approximately 35 percent CPD plasma and 65 percent platelet additive
      solution (T-Sol, Baxter). The WBC-reduction capacity of the filter, the recovery
      of cells after filtration, and the in vitro storage of RBCs (n = 10) and
      platelets (n = 6) were evaluated. RESULTS: Mean and maximum WBC counts after
      filtration were 0.08 x 10(6) and 0.3 x 10(6), respectively, per filtered whole
      blood unit. Recovery of RBCs (mean values) after filtration was 90 percent in
      whole-blood components and 73 percent in RBCS: Recovery of platelets (mean
      values) was 81 percent after filtration and 66 percent in PCS: The in vitro
      storage study of RBCs showed results comparable with previously published data,
      except for a lower degree of hemolysis. In the in vitro platelet storage study,
      results were compared with those of standard preparations. In all essentials,
      similar results were found. CONCLUSION: The results of the present study suggest
      that effective WBC reduction meets current standards and satisfactory recovery
      after filtration. The storage characteristics for RBCs and PCs are similar to
      those of standard preparations. Use of a whole-blood in-line filter to save
      platelets is a new option for whole-blood processing, which may simplify WBC
      reduction and blood component preparation, as well as reduce costs in the future.

PMID- 11316907
TI  - Influence of temperature, filter wettability, and timing of filtration on the
      removal of WBCs from RBC concentrates.
AB  - BACKGROUND: The efficacy of the removal of WBCs from buffy coat-reduced RBC
      concentrates by filtration is determined by many variables. The aim of this study
      was to investigate the influence of the filtration temperature, the wettability
      of the filter material, and the timing of the filtration after collection. STUDY
      DESIGN AND METHODS: The investigation used commercially available filters: 3 dry
      "online" filters (Cellselect FR, Fresenius Hemocare; BioR-01-max, Fresenius;
      Leucoflex LCG1, MacoPharma) and one wet "inline" filter (Leucoflex LCR4,
      MacoPharma) that contained saline-adenine-glucose-mannitol additive solution for
      RBCs and differed from the online version only in wettability. After buffy coat
      removal and suspension in saline-adenine-glucose-mannitol, filtrations were
      performed immediately at room temperature (RT) and after 2 hours' storage of the
      RBC concentrates at 4 degrees C, while the Leucoflex LCR4 was also tested after
      24 hours' storage of the RBC concentrates at 4 degrees C. Sets of 12 pooled
      experiments were performed to prevent donor-dependent differences. RESULTS: The
      Cellselect FR gave significantly better WBC removal from RBC concentrates at 4
      degrees C than at RT, with residual WBCs of 1.44 +/- 0.58 x 10(6) and 2.78 +/-
      1.23 x 10(6), respectively (p<0.001). The BioR-01-max gave no significant
      difference: 0.62 +/- 0.27 x 10(6) WBCs (at 4 degrees C) versus 0.61 +/- 0.25 x
      10(6) WBCs (at RT). Filtration with the Leucoflex LCG1 resulted in 0.06 +/- 0.03
      x 10(6) and 0.07 +/- 0.07 x 10(6) WBCs at 4 degrees C and RT, respectively, which
      is not a significant difference. The Leucoflex LCR4, however, gave 2.08 +/- 0.84
      x 10(6) WBCs at RT, 0.52 +/- 0.44 x 10(6) WBCs at 4 degrees C after 2 hours'
      cooling, and 0.05 +/- 0.10 x 10(6) WBCs at 4 degrees C after 24 hours' cooling
      (all p<0.001). CONCLUSION: Temperature, filter wettability, and timing of
      filtration after collection influence the efficacy of a filter for RBC
      concentrates. These variables need to be established, validated, and controlled
      before a filter can be selected for routine use.

PMID- 11316908
TI  - In vitro and in vivo measurements of gamma-radiated, frozen, glycerolized RBCs.
AB  - BACKGROUND: Transfusion-associated GVHD results from the presence of viable
      lymphocytes in transfused allogeneic blood components. Viable immunocompetent
      lymphocytes have been detected in RBCs that were frozen with glycerol and washed
      before transfusion. STUDY DESIGN AND METHODS: The study reported here assessed
      the effect of irradiation on human RBCs frozen with 40-percent (wt/vol) glycerol
      and stored at -80 degrees C. In vitro and in vivo testing was done on human RBCs
      that were frozen with 40-percent (wt/vol) glycerol at -80 degrees C, with some
      units exposed to 2500 cGy of gamma radiation and others not irradiated, and that,
      after thawing and washing, were stored in a sodium chloride-glucose solution at 4
      degrees C for 3 days before autologous transfusion. RESULTS: The glycerol-frozen
      RBCs treated with 2500 cGy before deglycerolization had a mean freeze-thaw-wash
      recovery of 87 percent and a mean 24-hour posttransfusion survival of 86 percent
      after storage for 3 days at 4 degrees C in a 0.9-percent NaCl and 0.2-percent
      glucose solution. For the nonirradiated units, the mean freeze-thaw-wash recovery
      was 85 percent and the mean 24-hour posttransfusion survival was 83 percent.
      CONCLUSION: These data show similar, acceptable results for RBCs frozen with 40
      percent (wt/vol) glycerol at -80 degrees C and treated in the frozen state with
      2500 cGy of gamma radiation and for RBCs that were not irradiated, all of which
      were washed and then stored in a sodium chloride-glucose solution for 3 days
      before autologous transfusion.

PMID- 11316909
TI  - Effect of rejuvenation and frozen storage on 42-day-old AS-1 RBCs.
AB  - BACKGROUND: The FDA has approved a 42-day storage period for RBCs stored in ADSOL
      (AS-1). This study was undertaken to provide data for the FDA about the
      feasibility of salvaging AS-1 RBCs at the end of their storage period by
      rejuvenation and freezing. STUDY DESIGN AND METHOD: The investigation, consisting
      of a study (n = 10) and control (n = 6) arm, was carried out in two centers. In
      both centers, eight healthy volunteers donated a unit (450 mL) of whole blood.
      The RBC concentrates were stored at 4 degrees C in AS-1 for 42 days. The study
      units were rejuvenated, whereas the control units were not. All units were stored
      frozen at -80 degrees C, then deglycerolized and kept for an additional 24 hours
      at 4 degrees C. RESULTS: After the 42-day storage period, ATP had declined to 62
      percent of the original value, 2,3 DPG was zero, and MCV was significantly larger
      than that of fresh RBCS: Following rejuvenation and deglycerolization, the mean
      ATP level was 141 percent, the mean 2,3 DPG level was 109 percent, and the MCV
      was normal. The freeze-thaw-wash recovery of the rejuvenated and nonrejuvenated
      RBCs was similar, 88.4 and 84.0 percent, respectively. There was no difference in
      hypoxanthine, inosine, and uric acid levels in the rejuvenated and nonrejuvenated
      units, which indicated that the chemicals in the rejuvenation solution and their
      by-products had been removed during processing. In both centers, the mean 24-hour
      survival of rejuvenated, deglycerolized RBCs exceeded 75 percent, whereas that of
      nonrejuvenated RBCs did not. The long-term survival rates of viable study and
      control RBCs were similar. CONCLUSION: Forty-two-day-old AS-1 RBCs that have been
      rejuvenated and then frozen have more than 75 percent viability and normal oxygen
      delivery function. Rejuvenation of RBCs does not introduce additional safety
      hazards to blood transfusion.

PMID- 11316910
TI  - Diethylenetriaminopentaacetic acid is unsuitable for long-term preservation of
      RBCs.
AB  - BACKGROUND: The addition of an appropriate metal chelator, such as
      diethylenetriaminopentaacetic acid (DTPA) to stored blood has been shown to be
      effective in a short-term (0-12 days) prevention of lipid peroxidation of stored
      RBCS: However, its long-term effectiveness has not been carefully evaluated.
      STUDY DESIGN AND METHODS: Blood was preserved in simulated blood bank conditions
      with or without the addition of DTPA for 4 weeks. Aliquots of stored blood were
      taken weekly from the storage bag and the deformability profile was determined
      using a custom-built laser viscodiffractometer. Malondialdehyde (MDA), an index
      of lipid peroxidation, and the extent of vesiculation of the stored blood were
      quantified concurrently. RESULTS: It was found that MDA values for DTPA
      supplemented blood at the end of a 28-day storage period were significantly
      elevated compared with the DTPA-free counterpart (23.50 +/- 3.2 vs. 16.10 +/- 2.5
      microM; p<0.05). In addition, DTPA-supplemented blood was more susceptible to
      vesiculation than its DTPA-free counterpart (31.26 +/- 4.1 vs. 10.26 +/- 1.5% of
      acetyl cholinesterase release, p<0.001). These data are also in accordance with
      the finding of the deformability profile result, indicating that DTPA
      supplemented blood exhibits not only a decrease in deformability index, but also
      a tendency to shift the profile to a lower osmolality compared with that of
      controls (a dehydration phenomenon). CONCLUSION: Long-term (0-28 days)
      preservation of human RBCs with DTPA caused a gradual increase in MDA production,
      a progressive enhancement of the severity of vesiculation, and an alteration in
      the deformability profile. Free-radical-mediated oxidative damage is likely to be
      the culprit for this observed phenomenon. In addition, the direct effect of DTPA
      on RBC structural integrity must be considered.

PMID- 11316911
TI  - Prevention of posttransfusion CMV in the era of universal WBC reduction: a
      consensus statement.

PMID- 11316912
TI  - Serial measurement of clotting factors in thawed plasma stored for 5 days.

PMID- 11316914
TI  - Venipuncture nerve injuries after whole-blood donation.

PMID- 11316916
TI  - Benefit of ADP receptor antagonists in atherothrombotic patients: new evidence.
AB  - In the Clopidogrel versus Aspirin in Patients at Risk of Ischaemic Events
      (CAPRIE) trial, clopidogrel showed a statistically significant superiority over
      aspirin in the prevention of ischaemic stroke, myocardial infarction and vascular
      death in patients with symptomatic atherosclerosis. More recently, post-hoc
      analysis of the data also showed that repeat hospitalization for ischaemic or
      bleeding events was decreased with clopidogrel compared with aspirin.
      Complementary analyses show that the benefit of clopidogrel over aspirin is
      amplified in a large population at very high risk of further atherothrombotic
      events (diabetics, patients with high cholesterol, and patients with previous
      manifestations of atherothrombosis). A potential clinically useful advantage of
      clopidogrel is its low propensity for adverse interaction with angiotensin
      converting enzyme (ACE) inhibitors, contrary to what may be seen with aspirin, as
      observed in a post-hoc CAPRIE analysis. The putative aspirin-ACE inhibitor
      interaction is being tested prospectively in the Warfarin and Antiplatelet
      Therapy in Chronic Heart Failure (WATCH) trial - a randomized comparison of
      warfarin, clopidogrel and aspirin in patients with chronic heart failure. The
      good gastrointestinal tolerance of clopidogrel seen in CAPRIE has been further
      demonstrated in a study in healthy volunteers where there was a markedly lower
      gastroduodenal erosion score after 8 days' administration of clopidogrel 75
      mg/day compared with aspirin 325 mg/day (p < 0.001). Following the positive
      findings obtained with clopidogrel plus aspirin in the Clopidogrel Aspirin Stent
      International Cooperative Study (CLASSICS) trial, other studies of clopidogrel
      plus aspirin have been initiated or are planned. These include Management of
      Atherothrombosis with Clopidogrel in High-risk patients (MATCH), a randomized
      comparison of clopidogrel plus aspirin versus clopidogrel in high-risk patients
      with recent stroke or transient ischaemic attack.

PMID- 11316915
TI  - Atherothrombosis: a major health burden.
AB  - Atherosclerosis involves structural change to the intima and media of medium- and
      large-sized arteries. Although an atherosclerotic plaque may remain clinically
      silent, it is prone to disruption, leading to local platelet activation and
      aggregation. Therefore, the major complication of atherosclerosis is thrombosis,
      with local occlusion or distal embolism - a generalized disease process known as
      atherothrombosis. The three main clinical manifestations of atherothrombosis are
      coronary heart disease (myocardial infarction and angina), peripheral arterial
      disease and cerebral ischaemia. Atherothrombosis is a leading cause of mortality,
      and stroke is the leading cause of disability in adults, the second most
      important cause of dementia and the third most common cause of death in Western
      countries. Ischaemic stroke accounts for 80% of strokes and atherothrombosis
      accounts for approximately 20% of all strokes. Criteria for atherothrombotic
      stroke are evidence of a 50% (or greater) stenosis of a cervical artery and
      exclusion of other potential causes. The incidence of cerebrovascular events is
      2,900 per million inhabitants per year, consisting of 500 transient ischaemic
      attacks and 2,400 strokes, of which 75% are first-ever stroke. The prevalence of
      stroke in the same population is 12,000, of which 800 patients (7%) per year have
      recurrences. The risk of ipsilateral stroke is 5% per year and the risk of a
      cardiac event is higher at 7%. Besides optimal management of risk factors for
      atherothrombosis and carotid surgery, antiplatelet therapy is the cornerstone of
      vascular prevention. In secondary prevention, antiplatelet agents are effective
      in reducing the risk of further ischaemic events in patients with
      atherothrombosis. Clopidogrel, a newly licensed ADP receptor antagonist, is the
      only antiplatelet agent to have demonstrated its superiority versus aspirin for
      the reduction of major ischaemic events (myocardial infarction, ischaemic stroke,
      vascular death) in patients whose initial manifestation of atherothrombosis was
      one of the three main clinical manifestations of the disease (recent ischaemic
      stroke, myocardial infarction, established peripheral arterial disease).

PMID- 11316917
TI  - Current oral antiplatelet agents to prevent atherothrombosis.
AB  - Aspirin inhibits platelet activation by irreversibly inhibiting platelet
      cyclooxygenase and thromboxane production, and reduces the odds of serious
      vascular events (stroke, myocardial infarction or vascular death) by about one
      quarter in a range of patients with symptomatic atherosclerosis at high risk of a
      subsequent event. The adenosine diphosphate (ADP) receptor antagonists
      clopidogrel and ticlopidine are significantly more effective than aspirin in high
      risk vascular patients, further reducing the odds of serious vascular events by
      about 10% (95% CI 2-19%) over the benefit provided by aspirin. The ADP receptor
      antagonists are also associated with a significant 30% reduction in the odds of
      gastrointestinal haemorrhage (odds ratio 0.71, 95% CI 0.59-0.86). Ticlopidine
      increases the odds of skin rash and of diarrhoea by more than twofold compared
      with aspirin, whereas clopidogrel is associated with a one-third increase in the
      odds of rash and of diarrhoea. Only ticlopidine increases the odds of neutropenia
      compared with aspirin. There is no clear evidence as yet for the benefit of
      dipyridamole or an oral GP IIb/IIIa receptor antagonist as single antiplatelet
      agents in atherothrombotic patients. Amongst high vascular risk patients, the
      combination of low-dose aspirin and high-dose dipyridamole is associated with
      about a 10% (95% CI 0-20%) reduction in the odds of a serious vascular event.
      Most of this reduction is due to a 23% reduction in non-fatal stroke. The size of
      this estimate continues to be investigated in an ongoing study of patients with
      transient ischaemic attack and stroke. The combined use of aspirin and
      ticlopidine is markedly superior to heparin, warfarin and aspirin for reducing
      thrombotic complications after coronary artery stenting. Clopidogrel plus aspirin
      has been shown to be safer than aspirin and ticlopidine in coronary stenting, and
      is now under long-term evaluation in unstable angina, and other conditions in
      which patients are at high risk of atherothrombotic events.

PMID- 11316918
TI  - Management practices in carotid stenting.
AB  - Carotid endarterectomy can be regarded as the standard of care for low-risk
      patients with severe carotid stenosis; however, this technique is less
      appropriate for certain patient groups. For high-risk patients, carotid stenting
      currently represents a suitable alternative to endarterectomy. The major cause of
      morbidity and mortality linked to carotid intervention is release of plaque
      material, which leads to microembolic obstruction of distal intracranial branch
      vessels and arterioles. Emboli retrieval devices are in development to help
      prevent distal occlusion, and effective antiplatelet therapy has a role in
      mitigating the clinical consequences of microembolization. Initial experience has
      shown that antiplatelet therapy with the adenosine diphosphate receptor
      antagonist clopidogrel plus aspirin (+/- abciximab) is associated with a very low
      risk of procedural stroke or stent thrombosis and does not appear to increase the
      risk of intracranial haemorrhage. The availability of potent antiplatelet
      regimens, emboli prevention devices and nitinol stents will greatly expand the
      spectrum of carotid disease that can be safely treated with endovascular therapy.

PMID- 11316919
TI  - Future perspectives for optimizing oral antiplatelet therapy.
AB  - Secondary prevention of stroke and other manifestations of atherothrombosis is
      essential if the burden of disease associated with these events is to be reduced.
      Therefore, it is important to identify patients most likely to benefit from
      antiplatelet therapy. There is a good rationale for combining antiplatelet agents
      with different modes of action, since different signalling pathways contribute to
      platelet activation. Based on the promising results obtained with an adenosine
      diphosphate receptor antagonist-aspirin combination in coronary stenting, several
      additional trials with clopidogrel plus aspirin are ongoing. They include CURE
      (Clopidogrel in Unstable angina to prevent Recurrent Events, in unstable angina
      and non-Q-wave myocardial infarction) and COMMIT (in acute myocardial
      infarction), which compare clopidogrel with placebo in patients receiving
      aspirin, and CREDO (Clopidogrel for Reduction of Events During extended
      Observation), a 1-year treatment follow-up to the clopidogrel arms of the
      CLASSICS trial (Clopidogrel Aspirin Stent International Cooperative Study).
      Planned trials with clopidogrel in neurology include SPS3 (Secondary Prevention
      of Small Subcortical Strokes, in patients with symptomatic lacunar stroke), and
      MATCH (Management of Atherothrombosis with Clopidogrel in High-risk patients, in
      patients with stroke or transient ischaemic attack plus one additional risk
      factor), which will compare the efficacy of clopidogrel plus aspirin versus
      clopidogrel in reducing important ischaemic events. Combination therapy with an
      oral glycoprotein (GP) IIb/IIIa receptor antagonist plus aspirin has so far been
      less promising. Trials of three compounds--orbofiban, xemilofiban and sibrafiban-
      in combination with aspirin for secondary prevention in cardiac patients have
      reported increased mortality compared with aspirin alone. A similar effect was
      seen when sibrafiban monotherapy was compared directly with aspirin alone. Trials
      of newer oral GP IIb/IIIa inhibitors are under way or are planned. The
      combination of dipyridamole plus aspirin appears to be superior to aspirin alone
      for the prevention of stroke in patients with stroke or transient ischaemic
      attack; the effectiveness of this combination is being further investigated in
      ESPRIT (European/Australian Stroke Prevention in Reversible Ischaemia Trial).

PMID- 11316920
TI  - Patterns of consumption.

PMID- 11316921
TI  - The use of drugs within the techno party scene in European metropolitan cities.
AB  - In 1998, a total of 3,503 visitors of techno parties in Amsterdam, Berlin,
      Madrid, Prague, Rome, Vienna and Zurich were interviewed. With this data, a
      subtly differentiated portrait of the techno party visitor was drawn, especially
      with a view to his/her involvement in the scene and the use of psychotropic
      substances. First of all, the results show that the use of illegal substances
      such as cannabis, ecstasy, amphetamines and cocaine is relatively widespread in
      the examined techno party scenes. A central characteristic of the drug use could
      be described as the polydrug occasional user model characterised by the
      occasional use of diverse substances that are usually taken together. The
      significance of the findings is discussed with regard to the practice of drug
      prevention.

PMID- 11316922
TI  - Sociodemographic and psychological characteristics associated with smoking among
      Greek medical students.
AB  - This study aims to investigate associations between sociodemographic and
      psychological characteristics and smoking among Greek medical students. The
      students studied were separated into four groups: non-smokers and occasional,
      regular and heavy smokers. The students completed a battery of inventories and
      checklists. Immigrant students, users of other psychoactive substances, students
      more prone to minor delinquency and students with high scores on activity level,
      approach to new situations, sociability and novelty seeking showed higher smoking
      rates. A better understanding of these differences could be useful for the
      planning of antismoking policy.

PMID- 11316923
TI  - Observation of psychoactive substance consumption: methods and results of the
      French OPPIDUM programme.
AB  - This study presents a French programme designed to observe and evaluate
      psychoactive substance dependence and abuse. Annual surveys lasting 4 weeks are
      performed with drug users in drug centres. Its usefulness is discussed using
      examples from the study: potential for antidepressant dependence (amineptine),
      monitoring benzodiazepine use and consumption associated with maintenance
      treatments. Flunitrazepam is the most consumed benzodiazepine and often got by
      deal (29%). There are important differences between buprenorphine consumption in
      a maintenance treatment context (9/10) and beyond this context (1/10). The main
      methodology problems encountered are representativeness and validity of data. The
      limits of the programme and its role in the French health care system are
      discussed.

PMID- 11316924
TI  - Myocardial Infarction associated with methadone and/or dihydrocodeine.
AB  - Chest pain and myocardial infarction occurring in young people with
      angiographically normal coronary arteries is well documented. Opiates have a
      cardioprotective effect and are used in acute heart attacks. We described a 22
      year-old opioid addicted male patient who suffered a myocardial infarction
      following the consumption of methadone and dihydrocodeine.

PMID- 11316925
TI  - Multiple access to sterile syringes for injection drug users: vending machines,
      needle exchange programs and legal pharmacy sales in Marseille, France.
AB  - OBJECTIVE: In Marseille, southeastern France, HIV prevention programs for
      injection drug users (IDUs) simultaneously include access to sterile syringes
      through needle exchange programs (NEPs), legal pharmacy sales and, since 1996,
      vending machines that mechanically exchange new syringes for used ones. The
      purpose of this study was to compare the characteristics of IDUs according to the
      site where they last obtained new syringes. METHODS: During 3 days in September
      1997, all IDUs who obtained syringes from 32 pharmacies, four NEPs and three
      vending machines were offered the opportunity to complete a self-administered
      questionnaire on demographics, drug use characteristics and program utilization.
      RESULTS: Of 485 individuals approached, the number who completed the
      questionnaire was 141 in pharmacies, 114 in NEPs and 88 at vending machines
      (response rate = 70.7%). Compared to NEP users, vending machine users were
      younger and less likely to be enrolled in a methadone program or to report being
      HIV infected, but more likely to misuse buprenorphine. They also had lower
      financial resources and were less likely to be heroin injectors than both
      pharmacy and NEP users. CONCLUSIONS: Our results suggest that vending machines
      attract a very different group of IDUs than NEPs, and that both programs are
      useful adjuncts to legal pharmacy sales for covering the needs of IDUs for
      sterile syringes in a single city. Assessment of the effectiveness and cost
      effectiveness of combining such programs for the prevention of HIV and other
      infectious diseases among IDUs requires further comparative research.

PMID- 11316926
TI  - Prevalence of tetraploid metaphases in semidirect and cultured chorionic villi.
AB  - OBJECTIVE: Investigation of the normal frequency of tetraploid metaphases in
      semidirect (STC) and cultured (LTC) chorionic villi. METHODS: Fifty metaphases in
      STC- and in LTC-villi slides of 100 women of advanced maternal age were screened
      for tetraploidy. RESULTS: Up to three tetraploid metaphases were encountered in
      27% of the STC-villi preparations; the scores fitted a Poisson distribution. In
      all LTC-villi preparations tetraploid cells were seen; the scores fitted a log
      Gaussian distribution. CONCLUSIONS: On the basis of these distributions, we
      propose a protocol for the management of tetraploid metaphases in chorionic
      villi, strongly reducing the number of prenatal follow-up investigations.

PMID- 11316927
TI  - Short rib-polydactyly syndrome type III: comparison of ultrasound, radiology, and
      pathology findings.
AB  - Short rib-polydactyly syndrome (SRPS; types I-IV) is an autosomal recessive,
      lethal skeletal dysplasia characterized by short-limb dysplasia, narrow thorax,
      and polydactyly. This syndrome is invariable and can be detected by 2-trimester
      ultrasound. The underlying gene has not been discovered yet. We report a case of
      SRPS subtype III Verma-Naumoff-Le Marec that was sonographically detected at 20
      weeks' gestation and compare prenatal ultrasound with postmortem findings from
      pathology and radiology. Since the risk of recurrence is 25%, early ultrasound
      for consecutive pregnancies was advised and performed at 11+6 weeks' gestation in
      the following pregnancy without any findings. Ultrasound diagnosis in this rare
      case of SRPS is a valuable tool for identification and early management, since
      there are no specific biochemical or histopathological markers for this syndrome.
      Radiological and pathological findings confirmed SRPS type III and assisted in
      the differential diagnosis of the subtype.

PMID- 11316928
TI  - Outcome in prenatally diagnosed fetal agenesis of the corpus callosum.
AB  - This study of the outcome and prognostic factors in prenatally diagnosed agenesis
      of the corpus callosum (ACC) was undertaken to see if there are any differences
      between subgroups, what relationship they have to neurodevelopmental outcome and
      whether this information aids the counselling of parents of fetuses with the
      condition. The outcome of 14 prenatally diagnosed fetuses with ACC and 61
      postnatally diagnosed patients was assessed in terms of clinical problems,
      developmental milestones and neurological signs; each patient was then given a
      score out of 10, 0 being a normal outcome and 10 being the worst outcome, i.e.
      death or termination of pregnancy. Comparing patients diagnosed pre- and
      postnatally, several similarities were found indicating that the postnatal group
      can provide useful information about the prenatal group. There was a higher
      incidence of ACC in males than females. In the prenatally diagnosed patients
      complete ACC was more common than partial ACC, although this might be because
      partial ACC was easily missed. Complete ACC has a worse prognosis than partial
      ACC (p = 0.001), and when associated with other anomalies, especially of the
      central nervous system, the outcome is very bad (p < 0.01). The only
      neurodevelopmentally normal patients were in the isolated partial ACC group. This
      study highlights the need to perform a detailed review of fetal anatomy and the
      desirability of determining the karyotype of the fetus in all newly diagnosed
      cases of ACC so that as much information as possible is available before parents
      are counselled about the likely outcome.

PMID- 11316929
TI  - First trimester diagnosis of split hand/foot by transvaginal ultrasound.
AB  - OBJECTIVE/METHOD: First trimester high-frequency transvaginal ultrasonographic
      examination was performed in a 26-year-old gravida 2, para 1, diagnosed with
      tetramelic split hands and feet. The couple was informed about the probable 50%
      recurrence risk of this anomaly. RESULTS: At 12 weeks' gestation, high-frequency
      transvaginal ultrasound examination revealed a fetus with biometry consistent
      with gestational age. Both hands appeared to have a single digit at the ulnar
      side. On the site of the metacarpal bones, only three bones could be visualized.
      Both feet showed two digits, with a typical 'split-foot' appearance. Nuchal
      translucency thickness measured 1.0 mm. No additional abnormalities could be
      found. The child was born in good condition with the described split hand/foot
      malformation (SHFM). CONCLUSION: This case report demonstrates prenatal
      sonographic diagnosis of SHFM in a first trimester fetus. In first trimester
      there can be several technical advantages and it shortens the period of
      uncertainty of the parents. Secondly it provides the option of early surgical
      termination of the pregnancy instead of induction of labour.

PMID- 11316930
TI  - Neonatal leukemoid reaction and early development of bronchopulmonary dysplasia
      in a very low-birth-weight infant.
AB  - The factors controlling the recruitment of inflammatory cells and the activation
      of the cytokine cascade in low-birth-weight premature infants have been
      implicated in the sequence of multiorgan inflammatory diseases, including the
      chronic lung disease of prematurity, bronchopulmonary dysplasia. This article
      describes a 982-gram, 25 (+2 days) weeks' gestation male infant, who had a
      leukemoid reaction throughout the first week of life, followed by early
      development of bronchopulmonary dysplasia.

PMID- 11316931
TI  - Different policies on prenatal ultrasound screening programmes and induced
      abortions explain regional variations in infant mortality with congenital
      malformations.
AB  - OBJECTIVE: To compare the impact of induced abortions (IA) on the mortality of
      infants with congenital malformations in four European regions with different
      policies on IA and prenatal ultrasound screening for congenital malformations.
      METHODS: A registry-based collection of data on congenital malformations in four
      different countries: Ireland (Dublin), Denmark (Funen County), Austria (Styria),
      and France (Strasbourg). RESULTS: The proportion of infant deaths with
      malformations ranged from 23 to 44% of all infant deaths with the highest
      proportion in Dublin, where IA is not allowed and prenatal ultrasound screening
      not performed. There were highly significant differences in the prevalences of IA
      (p < 0.001), fetal deaths (p < 0.01), and deaths in infants with congenital
      malformations (p < 0.001) between the four regions. The differences in total
      mortality with congenital malformations (IA + fetal deaths + infant deaths)
      between regions decreased, and only Strasbourg differs significantly from the
      other three regions. CONCLUSION: Prenatal ultrasound screening programmes have
      only a minor impact on total mortality with congenital malformations from 2nd
      trimester of pregnancy to 1 year of age, but seem to change the time of death
      which may be important for both the parents and the community.

PMID- 11316932
TI  - Bonding and coping with loss: examining the construction of an intervention for
      multifetal pregnancy reduction procedures.
AB  - Multifetal pregnancy reduction is a medical procedure by which pregnancies
      usually with three or more embryos are reduced in number early in gestation to
      improve their medical outcomes. A socially constructed intervention used as part
      of these procedures at Wayne State University is described. The intervention has
      as its goals the reduction of anxiety in the woman undergoing such a procedure
      and the refocusing of attention on the surviving 'twins' or singleton. Case
      materials from 36 cases are examined in detail to document how the intervention
      is being accomplished in practice, and how it may break down.

PMID- 11316933
TI  - Maternal serum Ca125 and Ca15-3 antigen levels in normal and pathological
      pregnancy.
AB  - OBJECTIVE: To evaluate the value of maternal serum CA125 and CA15-3
      concentrations for discriminating pathological from normal pregnancies. METHODS:
      Serum samples from 120 women, in whom pregnancy outcome was pathological, i.e.
      spontaneous abortion, fetal death, intrauterine growth retardation, chromosomal
      and structural abnormalities, and (pre)eclampsia, were assessed for CA125 and
      CA15-3 and compared with levels found in 350 women with a normal pregnancy
      outcome matched for age and duration of pregnancy. RESULTS: Maternal CA125 serum
      values were significantly higher in the first and the third trimester of
      pregnancy (median 23.0 and 21.0 U/ml; p < 0.00001 and p < 0.001, respectively),
      compared to those in the second trimester (median 14.0 U/ml), but not
      significantly different from those obtained in pathological pregnancies. Maternal
      serum CA15-3 values were significantly higher during the third trimester (median
      26.0 U/ml) compared to the first and second trimester of pregnancy (median 14.0
      and 15.0 U/ml; p < 0.0001); CA15-3 serum levels in normal and pathological
      pregnancies showed no significant difference. CONCLUSION: Maternal serum levels
      of CA125 are higher during the first and third trimester of pregnancy. CA15-3
      maternal serum levels are higher during the third trimester compared to the first
      and second trimester. Maternal CA125 and CA15-3 serum levels showed no relation
      with a pathological outcome of pregnancy.

PMID- 11316934
TI  - Growing of caecum and vermiform appendix during the fetal period.
AB  - OBJECTIVE: The aim of this study is to investigate the growing of the caecum and
      the vermiform appendix during the fetal period in human fetuses and the relation
      between growing and shape of the caecum and the localization of the vermiform
      appendix. METHODS: 40 male and 40 female externally normal-looking fetuses were
      studied between 10 and 40 weeks of gestation and were subdivided into fetuses of
      the 1st, 2nd, and 3rd trimesters and full-term fetuses. The parameters of
      interest included covering of the caecum with peritoneum, shape of the caecum
      (long tube, symmetric saccule, asymmetric saccule, extremely large right side-
      atypical), axial length and width of the caecum localization of the vermiform
      appendix, length of vermiform appendix and length of the meso-appendix. RESULTS:
      There was a difference in covering of the caecum with peritoneum between males
      and females; the caecum was predominantly tube shaped during the fetal period,
      with the asymmetric saccule towards the end of the fetal period; the localization
      of the vermiform appendix was subcaecal (39%) during the fetal period and
      postileal (34%) in female fetuses and subcaecal (48%) in male fetuses--the
      localization of the vermiform appendix changed according to the caecum shape
      during the fetal period; we found significant differences in the measurements of
      vermiform appendix, meso-appendix, and caecum among 1st-, 2nd-, and 3rd-trimester
      fetuses and full-term fetuses. CONCLUSIONS: There was an increase in the
      measurements for vermiform appendix, meso-appendix, and caecum with increasing
      gestational age; the localization of the vermiform appendix depended on the shape
      of the caecum, was different from that of adults and different between sexes, and
      there was also a significant difference in covering of the caecum with peritoneum
      between both sexes.

PMID- 11316935
TI  - Outcome of the prenatally diagnosed congenital cystic adenomatoid lung
      malformation: a Canadian experience.
AB  - Congenital cystic adenomatoid malformation of the lung (CCAM) is diagnosed by
      prenatal ultrasonography with an increasing frequency but controversy persists as
      to its prognosis and prenatal management. METHOD: A multi-institutional study of
      cases of CCAM diagnosed antenatally identified by ultrasonographers and by a
      review of hospital charts. RESULTS: We obtained 48 cases from five centers. We
      estimate the incidence of CCAM at 1:25,000 to 1:35,000 pregnancies. The incidence
      of voluntary abortions was 15% (7/48), of spontaneous abortions 2% (1/41) and of
      postnatal death 10% (4/40). One of the postnatal deaths was from trisomy 18. Of
      the 7 aborted fetuses, 2 had multiple malformations and 1 had severe hydrops and
      oligohydramnios; the other 4 had a large mass with mediastinal displacement but
      without hydrops. When pregnancy was allowed to continue, 56% of the lesions
      regressed spontaneously, even though one third of these had initial progression.
      In 17 cases (42%) the mediastinal shift corrected itself, sometimes by simple
      growth of the fetus but most often by a decrease in the size of the lung mass. In
      1 fetus, repeated needle decompressions followed by double-pigtail catheter
      drainage of large cysts allowed regression of hydrops. Despite this, neonatal
      death occurred from pulmonary hypoplasia. CONCLUSION: CCAM can lead to fetal or
      neonatal demise from hydrops, lung hypoplasia, prematurity or severe associated
      malformations, but has a good prognosis in the majority of cases.

PMID- 11316936
TI  - Nonspecific aerobic vaginitis and pregnancy.
AB  - During the period 1996-1998, cervical swabs of 50 pregnant women with subacute
      amniotic infection syndrome (AIS) and the semen of their consorts were
      bacteriologically analyzed. In the control group were 50 healthy pregnant women
      and their consorts too. Pathogenic bacteria (the most common were Escherichia
      coli, Staphylococcus haemolyticus, Chlamydia trachomatis and Ureaplasma
      urealyticum) were isolated from the cervical swab of 50 pregnant patients with
      AIS in 86.0% of them, while in the control group of healthy pregnant women in
      28.0%. Pathogenic bacteria were present in 70.0% of semen of consorts pregnant
      women with AIS and only in 30.0% of semen of the control group. The congruity of
      pathogenic bacteria in the cervical swab and semen in the investigated group was
      69.2%, while only 35.7% in the control group. Following erythromycin, cefuroxime
      and local tetracyclin treatment, the negativization of the cervical swab resulted
      in 30 pregnant patients with AIS, while the colonization persisted in 20 of them.
      The outcome of pregnancy was significantly better in cases with negativization of
      the cervical swab: perinatal loss was 6.7%, while in cases with persistent
      infection it was 55.0%. The authors presume the amniotic infection syndrome
      should be ascending manifestation of nonspecific vaginitis, which is maintained
      by the consort's urogenital infection. AIS should be classified as a 'sexually
      transmitted disease'.

PMID- 11316938
TI  - Educating speech-language pathologists for a multicultural world.
AB  - This paper presents critical elements and current needs in educating speech
      language pathologists for a multicultural world. A proposed paradigm shift in
      clinical teaching using the UK model is also introduced. In addition, a case
      study on the American Speech Language Hearing Association's efforts in
      implementing the Multicultural Action Agenda by networking with the Asian Pacific
      Islander caucus is described. A survey of multicultural elements in programs in
      Australia and New Zealand is included. Finally, suggestions for collaboration
      with those in established professional bodies to meet the increasing needs of a
      multicultural world are provided.

PMID- 11316939
TI  - Significance of cultural variables in assessment and therapy.
AB  - Language is a function of culture. Within the African culture traditional and
      faith healers play an essential role in counseling the community on various
      personal and communal health- and life-related conditions. This kind of practice
      is particularly observed among the native populations, among those less affected
      by Western influences, and among those who have less opposition from Western and
      Asian religions. It is in this context that diagnosis and treatment of the
      bilingual child with potential language disorders were examined from the point of
      view of the African culture. The present study examines the degree to which the
      traditional or/and faith healers diagnose and explain the nature of the child's
      problem to the parent(s). The impact of the African traditional healer is
      compared to the diagnosis made by the modern medical practitioner who adheres to
      the Cartesian dualism model which seeks to treat the patient by applying medical
      and surgical procedures. Speech-language pathologists need to recognize and
      consider the healer's impact on any child with a potential language disorder.

PMID- 11316940
TI  - Acquired alexia in multilingual aphasia and computer-assisted treatment in both
      languages: issues of generalisation and transfer.
AB  - This single-subject study addresses the issue of investigation and remediation of
      an acquired reading impairment observed in a Spanish-English bilingual speaker.
      Detailed bilingual reading testing showed parallel disturbances in the two
      languages, both from a qualitative and a quantitative point of view, with
      characteristics of letter-by-letter and aphasic alexia. On the basis of this
      mixed pattern, common to both languages, a two-step computer-assisted remediation
      programme was designed for English, then for Spanish, using a crossover AB-AB
      design. Therapy A consisted of tasks aimed at the inhibition of letter-by-letter
      reading. This was alternated with therapy B, which was designed to address
      phonological assembly. Results on therapy reveal transfer of gains when common
      reading processing are involved and language-specific gains with a greater
      benefit on the mother tongue when phonological representations are required in
      therapy and assessment. Consequences for language choice in bilingual aphasia
      therapy are discussed on the basis of these results.

PMID- 11316941
TI  - Verbal fluency in elderly bilingual speakers: normative data and preliminary
      application to Alzheimer's disease.
AB  - This study investigated verbal fluency abilities in 30 healthy elderly English
      Afrikaans bilingual speakers, and 6 bilingual subjects with Alzheimer's disease.
      Three 1-min semantic verbal fluency tasks (animals) were obtained in the
      bilingual mode, Afrikaans and English. Results were analysed in terms of total
      correct, and semantic clusters. There was no significant difference between
      monolingual and bilingual performance. Some healthy bilingual subjects used code
      switching as a strategy but with no direct increase in the number of exemplars
      generated, and there was no relationship between age of acquisition, pattern of
      use and verbal fluency scores. In comparison, subjects with Alzheimer's disease
      did not make use of code switching strategies, and there was some relationship
      between age of acquisition, pattern of use and verbal fluency scores.

PMID- 11316942
TI  - Cognitive and linguistic profiles of specific language impairment and semantic
      pragmatic disorder in bilinguals.
AB  - This study explored the notion that the extent to which language-impaired
      children can become bilingual depends on the type of language impairment. Single
      case studies were conducted on two 7-year-old bilingual children, who had both
      been exposed to English and Afrikaans consistently and regularly from an early
      age. The subjects presented with specific language impairment (SLI) and semantic
      pragmatic disorder (SPD), respectively. They were assessed on a battery of
      cognitive and linguistic tests in both their languages. Results indicate that the
      SLI subject, who presented with a deficit in successive processing on the
      Cognitive Assessment System, had difficulty in acquiring the surface features of
      both languages. She developed much better proficiency in English than in
      Afrikaans, despite substantial exposure to the latter. The SPD subject, whose
      cognitive profile was characterised by planning and attention deficits, but a
      strength in successive processing, presented with equal proficiency in both
      languages. The theoretical and clinical implications of this research are
      discussed.

PMID- 11316943
TI  - Comparison of cross-language generalisation following speech therapy.
AB  - Little is known about the phonological development of children who acquire two
      languages sequentially in the preschool years. Some of these children will be
      referred for assessment of speech disorder. Distinguishing between delayed
      development due to the language learning environment and disorder is problematic
      in the absence of normative data on the typical phonological development of
      bilingual children. Another major issue concerns whether both languages require
      intervention, or only one because of generalisation to the other language.
      Treatment efficacy studies of 2 bilingual children are reported. The data
      indicate that different patterns of cross-language generalisation occur depending
      upon the deficit in the speech processing chain underlying the speech disorder.

PMID- 11316944
TI  - Early reading for low-SES minority language children: an attempt to 'catch them
      before they fall'.
AB  - Minority language and low socioeconomic status (SES) students are at high risk
      for language and learning disabilities. In an attempt to 'catch them before they
      fall', an early reading project was initiated in four kindergarten classes, in a
      low-SES bilingual school (English/French as a second language), where minority
      language children form a majority. The project included: (1) teaching reading and
      writing to kindergarten students, and outcome research: individual pre- and post
      treatment assessment using a computer software to measure phonological processing
      and decoding skills; (2) reading testing of grade 1 students, graduates of
      traditional kindergartens with no explicit reading instruction programs.
      Statistical analyses of the pre- and post-tests showed that in only 9 weeks the
      kindergarten students were able to learn phonological skills critical to the
      reading process. By contrast, a significant number of the grade 1 students, all
      graduates of a traditional kindergarten, showed serious reading lags on a group
      reading test, indicating that early reading instruction is justifiable for this
      high-risk student population.

PMID- 11316945
TI  - Vascular biology of the isoprostanes.
AB  - Isoprostanes are a family of compounds produced from polyunsaturated fatty acids
      via a free-radical-catalysed mechanism. F(2)-isoprostanes are prostaglandin
      F(2alpha) isomers derived from arachidonic acid. These compounds induce potent
      vasoconstriction, mediated primarily by TP receptor stimulation, and in some
      vessels by the release of cyclooxygenase products. This vasoconstriction may be
      modulated by the endothelium through the release of NO. Potent vasoconstriction
      is also observed with E(2)-isoprostanes. Experimental and clinical data suggest a
      role for F(2)-isoprostanes in atherogenesis. These compounds can be detected in
      free forms in biological fluids as well as esterified in low-density lipoproteins
      or cell membranes. Their quantification represents a reliable marker of lipid
      peroxidation. Elevated levels of F(2)-isoprostanes in biological fluids in
      pathological conditions including atherosclerosis, ischaemia-reperfusion injury,
      and inflammatory vascular diseases, suggest a relationship between lipid
      peroxidation and such diseases. F(2)-isoprostanes are currently being
      investigated as non-invasive quantitative markers to monitor the response to anti
      oxidant treatment.

PMID- 11316946
TI  - Reduced PO(2) and adenosine formation preserve arteriolar nitric oxide synthesis
      during sympathetic constriction in the rat intestine.
AB  - Previous reports by this laboratory have indicated that a flow-dependent fall in
      arteriolar wall PO(2 )may be a stimulus for the sustained release of endothelial
      nitric oxide (NO) during sympathetic vasoconstriction in the superfused rat
      intestine. In this study, we tested the hypothesis that locally formed adenosine
      serves as the link between the fall in local PO(2) and NO synthesis under these
      conditions. Adenosine applied via pressurized micropipettes directly onto the
      wall or at a distance of 25 microm from the wall of first-order arterioles
      (resting diameter = 54 +/- 1 microm) elicited dose-dependent dilations of 15-46%
      that were significantly reduced by the NO synthase inhibitor N(G)-monomethyl-L
      arginine (L-NMMA, 10(-4) M). Arteriolar responses to sympathetic nerve
      stimulation were enhanced by 57-66% in the presence of L-NMMA or when tissue
      PO(2) was prevented from falling under a high O(2) superfusate. Adenosine
      deaminase (2.0 U/ml) or the selective A(1) receptor antagonist 8-cyclopentyl-1,3
      dipropylxanthine (4 x 10(-4) M) completely blocked the enhancing effect of L-NMMA
      on sympathetic constriction. These results are consistent with the hypothesis
      that the fall in arteriolar wall and/or tissue PO(2) that accompanies sympathetic
      arteriolar constriction in the rat intestine can lead to local adenosine
      production, which in turn preserves endothelial NO release.

PMID- 11316947
TI  - Circulating bone marrow cells can contribute to neointimal formation.
AB  - To examine the source of smooth muscle-like cells during vascular healing,
      C57BL/6 (Ly 5.2) female mice underwent whole body irradiation followed by
      transfusion with 10(6) nucleated bone marrow cells from congenic (Ly 5.1) male
      donors. Successful repopulation (88.4 +/- 4.9%) by donor marrow was demonstrated
      in the female mice by flow cytometry with FITC-conjugated A20.1/Ly 5.1 monoclonal
      antibody after 4 weeks. The arteries of the female mice were then subjected to
      two types of insult: (1) The iliac artery was scratch-injured by 5 passes of a
      probe causing severe medial damage. After 4 weeks, the arterial lumen was
      obliterated by a cell-rich neointima, with cells containing alpha smooth muscle
      actin present around the residual lumen. Approximately half of these cells were
      of male donor origin, as evidenced by in situ hybridization with a Y-chromosome
      specific probe. (2) In an organized arterial thrombus formed by inserting an 8-0
      silk suture into the left common carotid artery, donor cells staining with alpha
      smooth muscle actin were found in those arteries sustaining serious damage but
      not in arteries with minimal damage. Our results suggest that bone marrow-derived
      cells are recruited in vascular healing as a complementary source of smooth
      muscle-like cells when the media is severely damaged and few resident smooth
      muscle cells are available to effect repair.

PMID- 11316948
TI  - Identification and characterization of novel smoothelin isoforms in vascular
      smooth muscle.
AB  - Smoothelin is a cytoskeletal protein specifically expressed in differentiated
      smooth muscle cells and has been shown to colocalize with smooth muscle alpha
      actin. In addition to the small smoothelin isoform of 59 kD, we recently
      identified a large smoothelin isoform of 117 kD. The aim of this study was to
      identify and characterize novel smoothelin isoforms. The genomic structure and
      sequence of the smoothelin gene were determined by genomic PCR, RT-PCR and DNA
      sequencing. Comparison of the cDNA and genomic sequences shows that the small
      smoothelin isoform is generated by transcription initiation 10 kb downstream of
      the start site of the large isoform. In addition to the known smoothelin cDNA (c1
      isoform) we identified two novel cDNA variants (c2 and c3 isoform) that are
      generated by alternative splicing within a region, which shows similarity to the
      spectrin family of F-actin cross-linking proteins. Visceral organs express the c1
      form, while the c2 form prevails in well-vascularized tissue as analyzed by RT
      PCR. We then generated specific antibodies against the major smoothelin isoforms
      and could show by Western blotting and immunohistochemistry that the large
      isoform is specifically expressed in vascular smooth muscle cells, while the
      small isoform is abundant in visceral smooth muscle. These results strongly
      suggest that the smoothelin gene contains a vascular and a visceral smooth muscle
      promoter. The cell-type-specific expression of smoothelin isoforms that are
      associated with actin filaments may play a role in the modulation of the
      contractile properties of different smooth muscle cell types.

PMID- 11316949
TI  - Liposome-mediated high-efficiency transfection of human endothelial cells.
AB  - Liposome-mediated transfection of endothelial cells provides a valuable
      experimental technique to study cellular gene expression and may also be adapted
      for gene therapy studies. However, the widely recognized disadvantage of liposome
      mediated transfection is low efficiency. Therefore, studies were performed to
      optimize transfection techniques in human endothelial cells. The majority of the
      experiments were performed with primary cultures of human umbilical vein
      endothelial cells (HUVEC). In addition, selected experiments were performed using
      human brain microvascular endothelial cells and human dermal microvascular
      endothelial cells. To study transfection rates, HUVEC were transfected with the
      pGL3 vector, containing the luciferase reporter gene, complexed with several
      currently available liposomes, such as different Perfect Lipid (pFx) mixtures,
      DMRIE-C, or lipofectin. The optimal transfection rate was achieved in HUVEC
      transfected for 1.5 h with 5 microg/ml of DNA plasmid in the presence of 36
      microg/ml of pFx-7. In addition, transfection with the VR-3301 vector encoding
      for human placental alkaline phosphatase revealed that, under the described
      conditions, transfection efficiency in HUVEC was approximately 32%. Transfections
      mediated by other liposomes were less efficient. The usefulness of the optimized
      transfection technique was confirmed in HUVEC transfected with NF-kappaB or AP-1
      responsive constructs and stimulated with TNF or LPS. We conclude that among
      several currently available liposomes, pFx-7 appears to be the most suitable for
      transfections of cultured human endothelial cells.

PMID- 11316950
TI  - Hirulog-like peptide reduces balloon catheter injury induced neointima formation
      in rat carotid artery without increase in bleeding tendency.
AB  - Vascular restenosis is one of the major concerns for the management of coronary
      artery disease using therapeutic vascular procedures. Treatments with thrombin
      specific inhibitors, hirudin or hirulog-1, reduced ischemic events in coronary
      artery disease patients. Early started and prolonged infusions of these thrombin
      inhibitors partially prevented balloon catheter injury induced restenosis or
      neointima formation in experimental animal models, but increased the bleeding
      tendency. Hirulog-like peptide (HLP) was rationally designed to enhance the
      inhibition of the binding of thrombin to its receptor with less interruption of
      coagulation activity in comparison to hirulog-1. A single infusion of HLP for 4 h
      started 0.5 h before balloon catheter injury reduced neointima formation by 36%
      in rat carotid artery compared to vehicle controls. Tail bleeding time and
      activated partial thromboplastin time during HLP infusion were not significantly
      different from vehicle controls, but were significantly shorter than during
      heparin or hirulog-1 infusion. HLP treatment attenuated the expression of
      platelet-derived growth factor in the neointima of injured arteries. HLP also
      inhibited thrombin-induced thymidine incorporation in cultured baboon aortic
      smooth muscle cells. The findings suggest that HLP may substantially inhibit
      balloon catheter injury induced neointima formation without noticeable increase
      in bleeding tendency in rats. The inhibition by HLP of the expression of platelet
      derived growth factor and of the smooth muscle cell proliferation in the vascular
      wall potentially contributes to the preventive effect of the new thrombin
      inhibitor on injury-induced neointima formation in the vascular wall.

PMID- 11316951
TI  - Relationship between platelets and neutrophil adhesion and neointimal growth
      after repeated arterial wall injury induced by angioplasty in pigs.
AB  - Platelet and neutrophil interactions with injured vascular wall may contribute to
      restenosis. Their importance was mainly examined following balloon injury of
      intact arteries. However, dilation of diseased arteries is clinically more
      relevant and may elicit different responses. We investigated the relationship
      between platelets and neutrophil adhesion, neointima formation and P-selectin
      expression on damaged arteries after repeated balloon injury. In an acute single
      injury model, 8 pigs were subjected to bilateral carotid angioplasty and
      sacrificed 1 h later. In a chronic model, 19 pigs were subjected to similar
      procedures and allowed to recover for 4 weeks; then 18 arteries were redilated at
      the same previously injured sites (double injury) while the remaining arteries
      were not redilated and used to investigate the extent and the adhesive properties
      of the neointima. After single injury, (51)Cr-platelet adhesion (x10(6)/cm(2))
      increased significantly from 3.8 +/- 0.6 to 45.9 +/- 6.5 (p < 0.05) on mildly and
      deeply injured segments, respectively, and were statistically similar after
      double injury. After single injury, (111)In-neutrophil adhesion (x10(3)/cm(2))
      increased from 226.6 +/- 45.5 to 512.5 +/- 70.3 (p < 0.05) on mildly and deeply
      injured segments, and were significantly higher (p < 0.05) after double injury
      (mild: 1,289.1 +/- 227.9 and deep: 2,411.8 +/- 333.9). As well, the neo
      endothelium expresses P-selectin at 4 weeks and platelet and neutrophil adhesion
      was directly related to neointimal growth. These results, which indicate ongoing
      proinflammatory processes 1 month post-angioplasty, suggest that neutrophils may
      participate in the progression of restenosis.

PMID- 11316952
TI  - Intracellular distribution of gravin, a PKA and PKC binding protein, in vascular
      endothelial cells.
AB  - Gravin, a high-molecular-weight protein expressed widely in tissues and cells, is
      upregulated in cultured endothelial cells under conditions which suggest that it
      may play a role in wound repair and vascular development. In the current study,
      we examined the intracellular distribution of gravin to determine if it is
      associated with the cytoskeleton or with another intracellular compartment.
      Immunofluorescence microscopy of human umbilical vein endothelial cells (HUVEC)
      revealed that gravin had a punctate staining distribution that extended to the
      cell margin and did not appear to colocalize with stress fibers, microtubules,
      and intermediate filaments. Moreover, disruption of the cytoskeletal structures
      with either cytochalasin D or colchicine did not alter gravin distribution.
      However, confocal and immunoelectron microscopy clearly revealed that gravin was
      concentrated at the cell margin in close association with the plasma membrane.
      Immunoprecipitation of gravin from endothelial cell lysates resulted in
      coprecipitation of protein kinase activity that could be eluted from the
      immunoprecipitates with cAMP and that was inhibitable with a PKA-specific
      inhibitor. An anti-PKA catalytic subunit antibody reacted with a 40-kD band on
      immunoblots of the cAMP eluate. Immunoblots of the immunoprecipitates further
      revealed that PKCalpha coprecipitated with gravin from endothelial cell lysates.
      This study indicates that gravin is associated with either the plasma membrane or
      the membrane skeleton and may play a role in endothelial wound healing by
      targeting PKA and PKC to specific membrane-associated sites and regulating
      PKA/PKC-dependent cellular activities associated with endothelial wound healing.

PMID- 11316953
TI  - Differential effects of vascular endothelial growth factor-C and placental growth
      factor-1 on the hydraulic conductivity of frog mesenteric capillaries.
AB  - Vascular endothelial growth factors (VEGFs) are known to increase vascular
      permeability. VEGF-A acts on two receptor tyrosine kinases, VEGF receptor-1 (VEGF
      R1 or flt-1) and VEGF receptor-2 (VEGF-R2, flk-1 or KDR). VEGF-C acts only on
      VEGF-R2 on vascular endothelial cells, whereas placental growth factor-1 (PlGF-1)
      acts only on VEGF-R1. The effects of perfusion of these receptor-specific
      proteins on hydraulic conductivity (L(p)) was measured in frog mesenteric
      capillaries. The effect of PlGF on L(p) was not conclusive, and overall fluid
      flux did not increase during that time. VEGF-C acutely and transiently increased
      L(p) (4.5 +/- 0.9-fold), which was more obvious in a subset of vessels, in a
      similar manner to that reported for VEGF-A. In the subset of vessels in which
      VEGF-C significantly increased L(p) acutely, there was a sustained 12-fold
      increase in L(p) 20 min after perfusion, but this was not seen in those vessels
      which did not respond acutely to VEGF-C, or in vessels exposed to PlGF-1. L(p)
      was also increased 24 h after perfusion with VEGF-C, but not with PlGF-1. Western
      blot analysis showed that VEGF-R1 and VEGF-R2 are both present in frog tissue.
      These data show that the VEGFs that stimulate VEGF-R2 chronically increase L(p),
      but not those that stimulate VEGF-R1 only. This supports the hypothesis that
      chronic increases in microvascular permeability induced by VEGF are mediated via
      activation of VEGF-R2 rather than VEGF-R1.

PMID- 11316954
TI  - Meeting of the British Microcirculation Society. London, UK, April 11-12, 2000.

PMID- 11316955
TI  - Memory deficits in patients with DSM-IV obsessive-compulsive disorder.
AB  - Neuropsychological testing provides increasing evidence that certain memory
      deficits might play an essential role in the emergence of doubts and, as a
      result, in perpetuating checkers' rituals. Another account of doubting implicates
      meta-cognitive factors, such as confidence in memory. The present study examined
      mnestic functioning and self-perception of memory ability in a group of 27
      nondepressed patients with obsessive-compulsive disorder (OCD) and 27 normal
      controls. All patients met DSM-IV and ICD-10 criteria for OCD, displayed
      prominent behavioral checking rituals and had to show a score on the Yale-Brown
      Obsessive-Compulsive Scale (Y-BOCS) of at least 16. Significant deficits in
      intermediate (Lern- und Gedachtnistest; LGT-3) and immediate (Corsi Block-Tapping
      Test) nonverbal memory were identified in the patients with OCD compared to
      normal controls. Contrary to predictions, OCD patients also showed a significant
      deficit in general memory and verbal memory (LGT-3). With respect to meta
      cognition, OCD patients reported less confidence in their memories than controls.
      These findings suggest that obsessional doubt reflects a deficit in memory as
      well as a deficit in memory confidence. Depending on which dysfunction
      predominates, different therapeutic procedures seem to be required.

PMID- 11316956
TI  - Stability of DSM-III-R diagnoses: study of a case register.
AB  - We studied the diagnostic stability and the factors associated with it in 1,443
      psychiatric patients with multiple admissions for a period of 45 months. We
      successively considered the whole population, the psychotic and then the
      schizophrenic patients. Demographic and DSM-III-R diagnostic information was
      collected on a computerized database. During the observation period, 1,443
      patients were hospitalized twice or more. Diagnostic stability ranged from 34 to
      86%. Psychotic disorder was the most stable, whereas adjustment and anxiety
      disorders were the least stable. Among schizophrenic patients, higher stability
      appeared for residual and disorganized types (83 and 71%, respectively).
      Statistical analysis did not show any variable associated with change, apart from
      the diagnoses themselves. The reasons that could explain changes are discussed,
      as well as the clinical consequences of these shifts.

PMID- 11316957
TI  - Hyperventilation in panic disorder and social phobia.
AB  - The aim of our study was to observe the induction of panic attacks by
      hyperventilation in a group of panic disorder and social phobia patients (DSM
      IV). We randomly selected 26 panic disorder patients, 22 social phobics and 25
      normal volunteers. They were drug-free for 1 week. Hyperventilation (30
      breaths/min) was induced for 3 min. Anxiety scales were taken before and after
      the test. 61.5% (n = 16) of panic disorder patients, 22.7% (n = 5) of social
      phobics and 4.0% (n = 1) of control subjects had a panic attack after
      hyperventilating (p < 0.01, panic disorder vs. control; p < 0.05, panic disorder
      vs. social phobia; p = n.s., social phobia vs. control). Both anxiety disorder
      groups were more sensitive to hyperventilation than normal volunteers. The
      induction of panic attacks by voluntary hyperventilation may be an easy and
      useful test for validating the diagnosis in some specific panic disorder
      patients.

PMID- 11316958
TI  - Evaluation of the German version of the PTSD Symptom Scale (PSS).
AB  - The psychometric properties of the PTSD Symptom Scale (PSS) were evaluated in a
      clinical sample of severely injured in-patients after a traffic accident (n =
      123). The PSS contains 17 items which were derived from the DSM-III-R criteria of
      posttraumatic stress disorder (PTSD). The results indicate that the PSS has
      satisfactory reliability and validity (internal and external). The results are in
      correspondence with the results of Foa et al. using a sample of rape and non
      sexual-assault patients.

PMID- 11316959
TI  - Clinical validity of ICD-10 neurasthenia.
AB  - BACKGROUND: Neurasthenia was defined over a century ago. In view of a
      questionable clinical validity, it was omitted from the 3rd edition of the
      American Psychiatric Association's DSM, while it remains as an own diagnostic
      category in the WHO's ICD-10. The purpose of this study was, therefore, to
      examine the clinical validity of ICD-10 neurasthenia in a consecutive sample of
      chronic pain patients. PATIENTS AND METHODS: We included 193 patients (mean age
      45.1, SD +/- 10.2, 63% females) in the study. Psychiatric diagnoses were
      established by the use of ICD-10 Diagnostic Criteria for Research. In addition,
      the Screening List for Somatization Symptoms was administered: self-rating of 53
      medically unexplained somatic symptoms, and 11 additional screening questions
      concerning weakness after slight mental or physical exertion and disease
      conviction. RESULTS: Thirty-three percent of the patients who fulfilled the
      criteria of ICD-10 neurasthenia also fulfilled the criteria of ICD-10
      somatization disorder, 69% the criteria of ICD-10 undifferentiated somatoform
      disorder, 14% the criteria of ICD-10 hypochondriacal disorder, 66% the criteria
      of ICD-10 somatoform autonomic dysfunction, 85% the criteria of ICD-10 persistent
      somatoform pain disorder and 14% the criteria for sexual dysfunction not caused
      by organic disorder or disease. The symptom profile of ICD-10 neurasthenia was
      not clearly distinguishable from the symptom profiles of ICD-10 somatoform
      disorders and ICD-10 sexual dysfunction. DISCUSSION: Due to this substantial
      diagnostic overlap, the clinical validity of ICD-10 neurasthenia remains
      questionable.

PMID- 11316960
TI  - Misclassification of suicide-the contribution of opiates.
AB  - The reliability of suicide reporting remains a concern. Problems include
      procedural deficiencies, ambiguous evidence and the determination of intent. In
      this study, Queensland Suicide Register (QSR) data were compared to the usual
      official source - the Australian Bureau of Statistics (ABS). QSR deaths were
      coded as beyond reasonable doubt, probable and possible. These categories were
      analysed by methods and demographic variables to determine the nature of
      difficult-to-classify suicides. QSR suicides exceeded ABS especially for females,
      ages 25-44, and the methods overdose, drowning and 'other methods'. Opiate
      overdoses were most difficult to code. Ambiguous circumstantial information and
      unclear intent were major impediments. Nations witnessing rising rates of deaths
      due to drug abuse need to monitor undetermined and accidental deaths as well as
      suicides.

PMID- 11316961
TI  - Early behavioral development in autistic children: the first 2 years of life
      through home movies.
AB  - OBJECTIVE: The main aim of the research is to study the early behavioral
      development in autistic children through home movies. METHODS: fifteen home
      movies, regarding the first 2 years of life of autistic children are compared
      with the home movies of 15 normal children. The films of the two groups were
      mixed and rated by blind ratings with the Grid for the Assessment of Normal
      Behavior in Infants and Toddlers. The grid is composed of 17 items grouped into
      three developmental areas: social competence, intersubjectivity and symbolic
      activity. For every area, we have identified specific children's behaviors.
      RESULTS: Significant differences between the two groups are found both in the
      range of age 0-6 for intersubjectivity, and in the ranges of age 6-12 and 18-24
      for symbolic activity. CONCLUSIONS: The authors pose some hypotheses about an
      early-appearing impairment of intersubjectivity, the ability to represent other's
      state of mind, in subjects with autistic disorder.

PMID- 11316962
TI  - Relationship between subjective cognitive symptoms and frontal executive
      abilities in chronic schizophrenic outpatients.
AB  - The aim of this study was to investigate the relationship between executive
      abilities and subjective basic symptoms in a group of outpatients with
      schizophrenia. Fifty patients underwent a neuropsychological testing battery.
      Basic symptoms were assessed using the Frankfurt Complaint Questionnaire. Using
      Pearson's product-moment correlations or partial correlations calculated by
      regression procedure, cognitive performance was not related to subjective
      experience. When patients were divided into two groups, with and without
      'hypofrontality', as assessed by the neuropsychological testing, we did not find
      any significant difference in basic symptoms rating. Thus, it is likely that
      basic symptoms and neurocognitive functioning are unrelated in schizophrenic
      outpatients, probably because the expression of subjective experience and
      cognitive impairment is less pronounced than in inpatients. Also, subjective self
      perceived basic symptoms and neurocognitive functioning may be unrelated, because
      these concepts are based on different theoretical backgrounds.

PMID- 11316963
TI  - Temperament and disruptive behavior disorders.
AB  - In several studies on children with conduct disorder, difficult temperament in
      infancy was one of the major variables in the explanation of later aggressive
      behavior. According to these studies, subjects with a combination of high novelty
      seeking, low harm avoidance and low reward dependence (NS high, HA + RD low)
      should be most at risk for the development of disruptive behavior disorders. The
      Junior Temperament and Character Inventory was given to a clinical sample of 65
      adolescent patients of both sexes with the diagnoses of conduct disorder (with
      and without attention deficit hyperactivity disorder), emotional disorder
      (anxiety disorder, obsessive-compulsive disorder, depressive disorder), eating
      disorder (anorexia, bulimia) or personality disorder (borderline and narcissistic
      personality disorder). High novelty seeking and low harm avoidance were
      significantly correlated with externalizing symptoms like aggression and
      delinquency. In conduct-disordered children and adolescents, we found
      significantly higher scores of NS compared to the other clinical groups and the
      normative population, and significantly lower scores of harm avoidance compared
      to the other clinical groups, but not compared to the normative population. The
      relative risk of having a conduct disorder was markedly higher in those children
      and adolescents with elevated scores of novelty seeking.

PMID- 11316964
TI  - Charles Bonnet syndrome with auditory hallucinations: a diagnostic dilemma.
AB  - Charles Bonnet syndrome (CBS) appears to be commoner in elderly people than was
      previously thought. Nonetheless, as yet, no firm diagnostic criteria have been
      established for CBS, leaving the need for well-defined diagnostic criteria
      describing this syndrome unfulfilled. Two recently proposed diagnostic criteria
      for CBS insist on an absence of hallucinations in modalities other than visual.
      However, we experienced 2 cases suffering from probable CBS who experienced
      auditory hallucinations. In this report, we recommend that even if CBS coexists
      with other hallucinations, we should not exclude CBS as a probable diagnosis when
      the patients recognize their hallucinations as unreal. We believe that this
      modification of CBS diagnostic criteria will contribute to psychiatric
      epidemiology by correcting the current underestimation of CBS prevalence.

PMID- 11316965
TI  - Cutaneous photochemoprotection by green tea: a brief review.
AB  - Alarmingly increasing incidences of skin cancer are being reported from many
      countries where the majority of the population is Caucasian. According to
      projected estimates by the American Cancer Society, approximately 1.3 million
      cases of basal-cell and squamous-cell cancers, grouped together as nonmelanoma
      skin cancers, are diagnosed annually in the USA alone. It is clear that excessive
      exposure of the skin to solar radiation, particularly the UVB component, is
      responsible for these cancers. It is also important to mention here that among
      all the cancers, skin cancer is believed to be one of the most preventable and
      curable cancer types. While the surgical therapy for these skin cancers is highly
      effective, because of their recurrence and many other reasons, these cancers
      cause significant morbidity to the patients. One way to reduce the occurrence of
      these cancers is through chemoprevention. For the chemoprevention of photodamage
      and thus for photocarcinogenesis, we will use the term 'photochemoprotection'. In
      recent years, the naturally occurring compounds, especially the antioxidants,
      present in the common diet and beverages consumed by the human population have
      gained considerable attention as chemopreventive agents for potential human
      benefit. Many such agents have found a place in skin care products. Green tea,
      rich in polyphenolic antioxidants, is gaining increasing attention as a
      supplement in skin care products. In this short review, we will discuss the
      chemopreventive potential of green tea polyphenols against skin cancer,
      especially photocarcinogenesis. We advocate that the use of skin care products
      supplemented with agents such as green tea in conjunction with the use of
      sunscreens and educational efforts may be an effective strategy for reducing UV
      induced photodamage and skin cancer in humans.

PMID- 11316966
TI  - Azelastine tablets in the treatment of chronic idiopathic urticaria. Phase iii,
      randomised, double-blind, placebo and active controlled multicentric clinical
      trial.
AB  - This trial was designed to study the efficacy and tolerability of azelastine in
      controlling symptoms of chronic idiopathic urticaria, using ebastine as
      validation group. Fifty-two adult patients were randomised to receive azelastine
      (4 mg), ebastine (10 mg) or 18 placebo for 21 days. Patients were required to
      visit the investigating physicians on three different occasions (days 0, 7 and
      21). On each of these three study days, investigators assessed itching, wheals
      and erythema, based on a 4-point scale, and quality of life using a visual
      analogue scale and subscale 9 of the Short Form 36 (SF-36) Health Survey.
      Patients entered daily assessments of itching on diary cards also using a 4-point
      scale. Furthermore, investigators assessed global efficacy and tolerability of
      the study medication on day 21 or upon premature discontinuation of the trial.
      Side effects and compliance were evaluated on each visit. A statistically
      significant reduction in itching was found for both active treatments compared
      with placebo. These improvements, which were statistically significant already
      after 1 day of treatment, continued over the course of 3 weeks. Additionally,
      both azelastine and ebastine were effective in improving symptoms such as wheals
      and erythema when compared to placebo. The quality-of-life parameters were
      unaffected by either treatment. Taste perversion (2 cases) and somnolence (1
      case) were the only adverse drug reactions of azelastine. Ebastine, however,
      seemed to cause more often and more severe symptoms such as fatigue, sleepiness
      and asthenia. Global assessments of efficacy and tolerability performed by the
      investigators, also favoured azelastine. In conclusion, both azelastine and
      ebastine are effective and safe drugs, able to control symptoms of chronic
      idiopathic urticaria since the first day of treatment, and along a period of 3
      weeks.

PMID- 11316967
TI  - Scratching behavior in various strains of mice.
AB  - Scratching behavior was induced in 12 strains of mice and the frequency was
      compared. An injection of histamine at a dose of 50 nmol induced frequent
      scratching behavior only in ICR mice, although the same dose of serotonin induced
      frequent scratching behavior in all strains of mice except for A/J. Histamine (10
      nmol), serotonin (1 nmol), substance P (50 nmol) and passive cutaneous
      anaphylaxis induced significant vascular permeability increase in BALB/c, ICR,
      ddY and NC/Nga mice. These four stimuli also induced frequent scratching behavior
      in ICR mice. However, they failed to induce substantial increase in the incidence
      of scratching in the other three strains, except for ddY, which exhibited a
      slight but significant increase against substance P injection. These results
      suggest that the ICR mouse is a good responder for scratching behavior against
      various stimuli, especially against histamine. Thus ICR mice may be suitable for
      studying mediators and/or mechanisms for itching.

PMID- 11316968
TI  - Influence of piroxicam: hydroxypropyl-beta-cyclodextrin complexation on the in
      vitro permeation and skin retention of piroxicam.
AB  - The interactions between piroxicam (Px) and hydroxypropyl-beta-cyclodextrin
      (HPbetaCD) were thoroughly investigated both in solution and the solid state. The
      solubility studies have demonstrated the formation of a Px:HPbetaCD inclusion
      complex with 1:1 stoichiometry. The addition of propylene glycol to the medium
      produced less stable complexes, revealing the fact of this co-solvent probably
      acting as a competing agent. Equimolecular Px:HPbetaCD solid systems were
      prepared using the co-precipitation method and then fully characterized by X-ray
      diffractometry, infrared spectra and differential scanning calorimetry. A topical
      gel formulation containing Px, as inclusion complex with HPbetaCD, was developed
      in order to study the influence of Px complexation on its release rate and skin
      percutaneous permeation. The formation of Px:HPbetaCD complexes did not increase
      either Px release from the vehicle or its skin permeation. However, Px
      complexation with HPbetaCD allowed the incorporation of a higher quantity of Px
      into the gel, which resulted in a considerable increase in the Px released and
      permeated. Skin pretreatment with different HPbetaCD solutions, followed by the
      application of control gel, showed no enhancing capacity. The amount of Px
      retained in the skin, after pretreatment experiments, was found to be very
      similar to that obtained without skin pretreatment and was observed to be related
      to flux values through the skin.

PMID- 11316969
TI  - The relationship between neutrophils and incisional wound healing.
AB  - The systemic administration of granulocyte-macrophage colony-stimulating factor
      (GM-CSF) is used clinically to increase circulating neutrophils, but its wound
      healing effects after intraperitoneal treatment have not been studied yet. We
      planned to investigate the effect of neutrophils on wound healing under
      cyclophosphamide and GM-CSF treatment. Forty rats were divided into three groups:
      control group (group I, n = 12) receiving saline, group II (n = 14) receiving
      cyclophosphamide and group III (n = 14) receiving GM- CSF. The rats in all groups
      underwent incisional wounding and were euthanized after 7 days. Blood neutrophil
      counts and functions, tensile strengths and the hydroxyproline level of skin were
      determined, and a histopathological evaluation of healing was made. Neutrophil
      counts and phagocytosis significantly increased in group III and decreased in
      group II. Although the skin hydroxyproline level did not differ, there was a
      difference in tensile strength of the wounded skin between group II and group
      III. The wound score in group II was lower than that in groups III and I. As a
      result we suggest that systemically given GM-CSF - by increasing the neutrophil
      count and neutrophil phagocytosis index - can enhance the tensile strength of
      surgical incisions.

PMID- 11316970
TI  - EEMCO guidance for the assessment of transepidermal water loss in cosmetic
      sciences.
AB  - Measurement of transepidermal water loss (TEWL), based on the estimation of the
      water vapour gradient in an open chamber, is being used to support claims of
      cosmetics including product mildness, reduction in irritative skin reactions,
      skin hydration, skin repair, protective effect against UV damage and others. TEWL
      measurement can also screen ingredients that have a beneficial effect on the
      barrier function and offer the possibility to monitor in vivo, on human skin, the
      effect of topical treatment in an objective and non-invasive way. A high number
      of variables affecting TEWL measurements have been identified. These should be
      rigorously taken into consideration. To work under standardised conditions is of
      the utmost importance to obtain reliable and reproducible results.

PMID- 11316971
TI  - The pathophysiology, diagnosis and therapy of the transurethral resection of the
      prostate syndrome.
AB  - In this article, the authors analyze a syndrome first described by Creevy in the
      1940s, which may occur during a transurethral resection of the prostate (TURP).
      The syndrome is characterized by cardiocirculatory and neurological problems due
      to rapid changes in intravascular volume and plasma solute concentrations caused
      by excess irrigating fluid absorption. This article reviews the available
      literature and reports on the experience of our clinic, a specialist department
      in the physiopathology, diagnosis, therapy and prevention of TURP syndrome.

PMID- 11316972
TI  - Predictive value of radiological criteria for disintegration rates of
      extracorporeal shock wave lithotripsy.
AB  - OBJECTIVE: To evaluate routinely applicable criteria to predict fragmentation of
      renal calculi by extracorporeal shock wave lithotripsy (ESWL). PATIENTS AND
      METHODS: Two hundred and two consecutive patients (121 men, 81 women), median age
      48 (range 19-81) years, were treated with the original Dornier HM-3 lithotriptor
      at a single stone center. Inclusion criteria were: solitary stones, 10-30 mm in
      greatest diameter, located in renal pelvis or calyces. Based on plain
      radiographs, the calculi were classified according to their size, form, location,
      density (compared to the 12th rib), structure and surface. Furthermore, age of
      the patient, gender and body mass index were also considered for evaluation.
      Disintegration was documented on day 1 after ESWL by plain X-ray. A multivariate
      regression analysis was applied to all preoperative parameters, based on the dual
      variable stone free versus residual fragments. RESULTS: The overall
      disintegration rate was 95.5%; 42 patients (20.8%) were completely stone free,
      and 151 patients (74.7%) had clinically insignificant residual fragments (5 mm or
      smaller). 14.9% of men and 29.6% of women were stone free (p = 0.01). All other
      parameters did not reach statistical significance. CONCLUSIONS: The
      disintegration rate of the HM-3 is excellent for kidney stones; women did
      significantly better than men. However, because of this high disintegration rate,
      a much larger series would be necessary to define possible differences between
      preinterventional parameters, if there were any at all.

PMID- 11316973
TI  - PSA and second-line therapy of hormone refractory prostate carcinoma.
AB  - The aim of the present study was to correlate PSA response with subjective
      response (bone pain and performance status), in patients treated for hormone
      refractory carcinoma of the prostate. Twenty-four patients were introduced into
      the study. Median PSA was 198 ng/ml. Symptom score, performance status and PSA
      were monitored monthly for 3 months and then 3-monthly. Sixteen patients (66%)
      showed a PSA response (median value 10 ng/ml). In 8 patients (33%) PSA was <4
      ng/ml. Eight patients (33%) only had a subjective response. However, 75% of the
      patients with a PSA value <4 ng/ml had a subjective improvement. On the other
      hand, subjective response was 25% only in patients in whom PSA value decreased to
      <50% of the initial value but >4 ng/ml. In conclusion, PSA response is not always
      related to subjective improvement and does not always implicate a beneficial
      effect of the therapy for the patient.

PMID- 11316974
TI  - Optimal starting time for flutamide to prevent disease flare in prostate cancer
      patients treated with a gonadotropin-releasing hormone agonist.
AB  - OBJECTIVE: Flare-up phenomena, such as an increase in prostate-specific antigen
      (PSA) and/or deterioration of symptoms, are observed in some patients undergoing
      gonadotropin-releasing hormone (GnRH) agonist therapy. This study was carried out
      to determine the optimal time for starting the administration of flutamide to
      prevent flare-up phenomena. PATIENTS AND METHODS: Twenty-six patients with
      prostate cancer and elevated serum levels of PSA were randomly assigned to 5
      groups. Group A patients (n = 6) were treated with a subcutaneous injection of
      3.75 mg leuprorelin acetate depot alone. Group B, C, D and E patients (5 patients
      in each group) were treated with 375 mg/day of orally administered flutamide
      combined with leuprorelin. Flutamide was initiated on the day of leuprorelin
      injection in group B, and at 1, 2 and 4 weeks before leuprorelin injection in
      groups C, D and E, respectively. Serum PSA and testosterone levels were measured
      in each patient. RESULTS: Pretreatment with flutamide increased the serum
      testosterone level, but the testosterone surge after leuprorelin administration
      was almost the same in all 5 treatment groups. In patients who had been treated
      with flutamide in combination with leuprorelin, the mean PSA level did not exceed
      the pretreatment levels after leuprorelin administration. The rate of decrease in
      PSA in the group receiving simultaneous administration of flutamide with
      leuprorelin showed a decline comparable to that during the period before
      leuprorelin administration in the flutamide pretreatment groups. CONCLUSION:
      Simultaneous administration of flutamide with a GnRH agonist is sufficient to
      prevent flare-up phenomena.

PMID- 11316975
TI  - Differential expression of cytokines and cytokine receptors in renal cell
      carcinoma.
AB  - Modulation of immunomechanisms by tumor cells can be caused by secretion of
      cytokines. In vitro data are usually gained in culture systems. It is debatable
      whether these systems are representative of the conditions inside the respective
      tumor tissues. Immunohistochemical studies of tumor tissue cryostats were
      compared with those in matched primary renal cell carcinoma tumor cell cultures.
      Results were correlated with histopathological characteristics and the in vitro
      cytotoxic effect of autologous tumor infiltrating lymphocytes (TILs). Expression
      of all studied cytokines and cytokine receptors could be shown in cryostats and
      cell cultures, but the detection pattern varied individually. The
      immunohistochemical results in cryostats were in good accordance with those in
      cell cultures. Expression of TGFbeta1 both in cryostats and cell cultures
      significantly correlated with the lack of cytotoxic activity of autologous TILs.
      Representative data can be obtained in tumor culture systems of primary renal
      cell carcinoma. TGFbeta1 secretion could play an important role in the
      interactions between tumor and cytotoxic cells.

PMID- 11316976
TI  - 'Viagra effect' - influence of mass media on patient behavior.
AB  - INTRODUCTION: The effects of modern mass media and communication on the public
      health system are well known. So far however, these different influences of the
      media have not been objectively evaluated by physician-patient contacts. PATIENTS
      AND METHODS: In this study we asked urologists, primary care physicians and
      internists in private practices in Cologne and a rural area (Erftkreis, Germany)
      to quantify their weekly contacts with patients suffering from erectile
      dysfunction (ED). The poll was conducted by four separately mailed questionnaires
      whereas a double counting was avoided. Between the second and third mailing, an
      unbelievable public attention was seen following the FDA approval of Viagra in
      the United States. When Viagra was available in Germany, a fourth questionnaire
      was sent (4 months later) to all practitioners (n = 751). RESULTS: During this
      time span, there was a statistically (p <or= 0.01; t test) significant increase
      in weekly physician-patient contacts (WPC; 13.1-19.1 WPC for urologists, 4.4-5.5
      WPC for general practitioners/internists) for ED in the region of Cologne
      Erftkreis. In the fourth mailing, there was a slight decrease, but overall WPC
      was still higher compared to the first two mailings (17 WPC for urologists, 5.2
      WPC for other specialists). CONCLUSIONS: Our investigation shows that urologists
      are accepted as the competent advisory partners for therapy with Viagra. This was
      seen by the higher increase (20.1%) in patient contacts with urologists in
      comparison to colleagues of other medical disciplines (45.8 vs. 25.7% between
      mailing 1+2 and 3). In this investigation we were able to demonstrate the effects
      of mass media on patient behavior.

PMID- 11316977
TI  - Use of sildenafil in penile implant patients.
AB  - OBJECTIVE: To determine whether Sildenafil use in the patients with penile
      implants provided additional sexual satisfaction. MATERIAL AND METHODS: 12
      patients who had had insertion of inflatable penile implants were given oral
      Sildenafil in the period following implantation. They were assessed for sexual
      satisfaction before and after oral Sildenafil use. The assessment was done using
      questions 7, 8, 13 and 14 of the International Index of Erectile Function (IIEF)
      questionnaire. These four questions of the IIEF questionnaire address the domain
      of satisfaction in male sexual behavior. Each person answered these questions
      using a scale of 1 (almost never or never) to 5 (almost always or always). The
      main answer to each question after Sildenafil was compared to the mean answer
      before. RESULTS: There was a significant increase in the mean answer score to
      each of these questions. CONCLUSION: Supplemental Sildenafil can increase the
      sexual satisfaction of patients with inflatable penile implants.

PMID- 11316978
TI  - Nephrogenic adenoma of the urinary bladder: our experience and review of the
      literature.
AB  - OBJECTIVE: To assess our experience in the treatment and clinical outcome of
      bladder nephrogenic adenoma (NA) updating and reviewing the literature concerning
      this issue. PATIENTS AND METHODS: From September 1976 to June 1999, bladder NA
      was diagnosed in 8 patients: 6 men and 2 women with a 3:1 male ratio, aged 26-80
      (mean 58.3) years. Follow-up ranged from 4 to 194 (mean 93.5) months. RESULTS: NA
      was associated with transitional cell carcinoma in 3 cases. Predisposing factors
      were assessed in all patients. Previous surgery of the lower urinary tract was
      detected in 5 cases: ureterocystoneostomy in 2, partial cystectomy in 1, repair
      of vesicouterine fistula in 1, and multiple urethroplasties in 1. Previous
      endoscopic treatments were carried out in 2 patients, transurethral resection of
      the prostate in 1 and repeated transurethral resection of the vesicle in the
      other. A history of intravesical instillation of bacillus Calmette-Guerin was
      assessed in 1 case. Patients complained of irritative voiding symptoms in 6 cases
      and hematuria in 2. Endoscopically, the lesions appeared polypoid and multifocal
      in 5 patients, and flat and single in 3. The lesions were removed endoscopically,
      providing relief of symptoms in all cases. Histopathology assessed the diagnosis
      of nephrogenic adenoma, detecting focal atypic cells in 1 case only. Five
      patients (63%) relapsed 2-24 months after management. Recurrences were also
      treated endoscopically. CONCLUSIONS: Clinical and endoscopic features of bladder
      NA are not specific, simulating urothelial carcinoma or chronic cystitis.
      Endoscopic management allows accurate histological diagnosis and provides long
      lasting relief of symptoms. NA needs careful and long-term follow-up, because of
      the high risk of recurrences and the potential neoplastic degeneration of the
      metaplastic urothelium.

PMID- 11316980
TI  - The Ageing Male. A consensus statement from the joint multidisciplinary working
      group of the German Society of Andrology, the German Society of Dermatology, the
      German Society of Endocrinology and the German Society of Urology.

PMID- 11316979
TI  - Glycosaminoglycans: urinary excretion in children with myelomeningocele.
AB  - BACKGROUND: The main consequences of neurogenic bladder dysfunction are renal
      damage related to high intravesical pressure, vesicoureteral reflux (VUR) and
      urinary tract infections (UTIs). Neurologic impairment, UTIs and VUR are known to
      be linked with a potential for renal scarring. Of paramount importance as
      predisposing conditions for UTIs in neurogenic bladder are poor bladder drainage
      and detrusor-sphincter dyssynergy which cause further abnormalities on the
      internal bladder surface and, consequently, a bladder wall rich in
      glycosaminoglycans (GAGs). MATERIALS AND METHODS: The aim of this study is to
      investigate the correlation between GAG excretion and bladder wall degeneration
      in 43 patients affected by spina bifida (SB) and 40 healthy age-matched control
      children. RESULTS: The amounts of GAGs excreted vary greatly in SB patients aged
      from 0 to 5 years, and values are comparable to those observed in normal
      controls. They are significantly higher in children over 5 years of age.
      CONCLUSION: The increased excretion of GAGs in older SB patients is an important
      parameter in the evaluation of the physiopathological condition of the bladder
      wall and hence may be considered a possible marker for monitoring the beginning
      of bladder damage.

PMID- 11316981
TI  - Penile metastasis arising from transitional cell carcinoma of the urinary
      bladder.
AB  - Metastatic spread of transitional cell carcinoma of the bladder to the penis is
      very rare. We present 1 such case in a 63-year-old man that was treated by total
      penectomy and adjuvant systemic chemotherapy.

PMID- 11316983
TI  - Scrotal extraperitoneal hernia of the ureter: case report and literature review.
AB  - Ureteral herniation is a rare, often misdiagnosed event and serious surgical
      complications are possible. Until 1992, 128 cases of ureteral herniation were
      reported and in 54 (42%) the inguino-scrotal region was involved. From an
      anatomical and pathogenic standpoint, two types of uretero-inguinal hernias can
      be identified: paraperitoneal (more frequent, acquired, always presenting a
      peritoneal hernia sac, frequently associated with other herniated abdominal
      structures) and extraperitoneal (very uncommon, congenital, never associated with
      a true peritoneal sac, always composed only of the ureter). We describe a new
      case of scrotal extraperitoneal ureteral hernia and review the current
      urological, surgical and radiological literature to analyze the main clinical
      characteristics of this pathology and its ideal treatment.

PMID- 11316982
TI  - Vesico-ileal fistula caused by a foreign body.
AB  - An enterovesical fistula due to an intestinal foreign body is presented and the
      therapeutic aspects of the lesion are discussed.

PMID- 11316984
TI  - Bilateral transection of the vas deferens: an unusual trauma from a cross stab
      injury of the scrotum.
AB  - An unusual case of division of both vas deferens in a patient with a cross stab
      injury to the root of scrotum is described. The management of this case in the
      emergency setting is discussed. The case illustrates the need to explore every
      case of penetrating trauma to the scrotum, even in the absence of active
      bleeding, to avoid missing such injuries. These injuries, although not life
      threatening, can have a profound impact on the patient's future fertility and
      this may only manifest several years after the injury.

PMID- 11316985
TI  - Diagnosis of retrovesical ectopic and hyperplastic prostate tissue by transrectal
      needle biopsy.
AB  - We report on an ectopic prostate in a 50-year-old man. Transabdominal
      ultrasonography, pelvic computed tomography, and pelvic magnetic resonance
      imaging revealed a heterogeneous tumor 8 cm in diameter in contact with the
      posterior wall of the urinary bladder. The tumor was histologically confirmed to
      be a benign prostatic hyperplasia. This is the 3rd case of retrovesical ectopic
      prostatic tissue which was diagnosed by transrectal needle biopsy.

PMID- 11316986
TI  - Intrathoracic kidney in an adult.
AB  - An intrathoracic kidney, although rare, should be considered in a patient with a
      mass at the base of the lung on a chest radiograph. Excretory urography is
      diagnostic and may eliminate the need for further extensive investigation and
      operation.

PMID- 11316987
TI  - A tool for self-dilatation of distal urethral strictures.
AB  - We propose the use of a catheter stopper with a smooth tip as a tool for the
      dilatation of distal urethral strictures. This allows for self-dilatation by the
      patient himself or by non-professionals involved in daily care at regular
      intervals. The method was successfully used in 2 patients.

PMID- 11316988
TI  - What is the best method for urgent urinary diversion in patients with obstruction
      and infection due to ureteral calculi?

PMID- 11316989
TI  - New nephrostomic catheter.

PMID- 11316990
TI  - Sequencing antiretroviral drugs.

PMID- 11316991
TI  - Mutations in the non-nucleoside binding-pocket interfere with the multi
      nucleoside resistance phenotype.
AB  - OBJECTIVES: To investigate the genotypic and phenotypic effects of in vitro
      resistance selection with lamivudine and/or the second generation non-nucleoside
      reverse transcriptase inhibitor (NNRTI) quinoxaline HBY097 using HIV-1 isolates
      carrying the multi-nucleoside resistance pattern linked to the Q151M mutation.
      METHODS: Virus strains were selected in C8166 cells in the presence of increasing
      concentrations of lamivudine or HBY097. In parallel control experiments, the
      virus was cultured in C8166 cells in the absence of drugs. The entire reverse
      transcriptase encoding region was amplified using polymerase chain reaction and
      was subsequently sequenced. Antiviral activities of drugs were evaluated in C8166
      cells. RESULTS: High-level resistant viruses were selected rapidly in the
      presence of lamivudine and quinoxaline (less than 10 passages). The multi
      nucleoside resistance mutations were stable during in vitro resistance selection.
      Lamivudine elicited the acquisition of the M184I mutation. Phenotypic resistance
      to all nucleoside-analog reverse transcriptase inhibitors (NRTIs) was increased
      when M184I was added to the multi-nucleoside resistance background in the absence
      of NNRTI-resistance mutations. In most cases of HBY097 resistance selection, at
      least two mutations associated with NNRTI resistance resulted in high-level NNRTI
      resistance. The NNRTI resistance-related mutations partially reversed the
      phenotypic resistance to most NRTIs, except to abacavir. The addition of the
      M184I mutation to the NNRTI-multi-nucleoside resistance set abolished this
      antagonizing effect for didanosine, zalcitabine and lamivudine, but further
      potentiated the phenotypic reversal for zidovudine and stavudine. CONCLUSION:
      Changes in the non-nucleoside binding pocket must affect the conformation of
      residues at the dNTP binding site, and can result in a partial phenotypic
      reversal of the multi-nucleoside resistance phenotype.

PMID- 11316992
TI  - Inverse relationship between the titre of TT virus DNA and the CD4 cell count in
      patients infected with HIV.
AB  - OBJECTIVES: To investigate the prevalence and relative titre of TT virus (TTV)
      DNA, and to examine the relationship between the extent of TTV viraemia and the
      immune status among 144 patients with HIV infection; 178 age- and sex-matched
      healthy individuals were also studied. METHODS: TTV DNA was detected
      quantitatively by two distinct polymerase chain reaction (PCR) methods
      [untranslated region (UTR) and N22]. UTR PCR detects all TTV genotypes, and N22
      PCR can primarily detect four major TTV genotypes (1-4). RESULTS: Using UTR PCR
      and N22 PCR, respectively, TTV DNA was detected significantly more frequently in
      HIV-infected patients than in controls (99 versus 91%, P < 0.001; 56 versus 27%,
      P < 0.0001), and the relative titre (10N/ml) was significantly higher in HIV
      infected patients [4.5 +/- 1.2 (mean +/- SD) versus 3.1 +/- 0.9, P < 0.0001; 2.6
      +/- 1.5 versus 1.5 +/- 0.9, P < 0.0001]. Age, sex, co-infection with hepatitis B
      or C virus, and risk factors for HIV transmission did not appear to be
      significant factors associated with the titre of TTV viraemia. However, the titre
      of TTV DNA was significantly higher in HIV-infected patients with AIDS (P <
      0.0001), those with low CD4 T cell count (P < 0.0001), or those with high HIV
      viral loads (P = 0.0047). CONCLUSION: TTV is highly prevalent and high-titred in
      HIV-infected patients. The TTV viral load may reflect the degree of immune status
      of these immunocompromised hosts.

PMID- 11316993
TI  - Beta amyloid precursor protein and patterns of HIV p24 immunohistochemistry in
      different brain areas of AIDS patients.
AB  - OBJECTIVES: To evaluate the correlation between immunohistochemical positive
      patterns (globular and filamentous structures) of beta-amyloid precursor protein
      (beta-APP), used as a marker of axonal damage, and the different distribution of
      HIV p24 antigens, in three different brain areas of AIDS patients. METHODS:
      Eighteen AIDS patients with HIV-related brain lesions were included in the study.
      Forty-nine sections from basal ganglia, frontal cortex and hippocampus were
      selected. After microwave oven pre-treatment, the sections were incubated with
      anti-HIV p24 and anti-beta-APP monoclonal antibodies; the reactions were
      developed with peroxidase/3,3'diaminobenzidine. The positivity was graded by semi
      quantitative scores. Double immunohistochemical staining was used to evaluate the
      co-localization of the antigens. RESULTS: HIV p24 immunohistochemistry was
      positive in 44 of 49 sections (89%), with a prevalence of interstitial positive
      cells and positive microglial nodules in 27 and 13 sections respectively. beta
      APP-positive structures were demonstrated in 23 of 44 sections (52%) with HIV
      related lesions, and were absent from the five sections without viral expression.
      Globular and filamentous lesions were observed in 21 of 23 sections and 10 of 23
      lesions respectively. Moreover, a high grade of globular type lesion was related
      to an elevated presence of diffuse interstitial HIV p24-positive cells in basal
      ganglia; double immunohistochemical reactions demonstrated the co-localization of
      beta-APP globules and HIV p24 antigens. CONCLUSIONS: The data obtained confirm
      the coexpression of beta-APP and viral antigens in particular areas of the brain
      with HIV-related lesions; there is a strict correlation between beta-APP globules
      (indicating chronic cerebral damage) and the interstitial pattern of HIV p24
      immunohistochemistry.

PMID- 11316994
TI  - V3 variation in HIV-seropositive patients receiving a V3- targeted vaccine.
AB  - OBJECTIVE: To analyze V3 loop sequences of HIV-1 in three seropositive
      individuals who exhibited declines in viremia while receiving a V3-targeted
      vaccine. DESIGN: Retrospective analysis of case series at an HIV Clinic,
      University of Tel Aviv. PATIENTS: Three HIV-1-seropositive, PPD-DTHR-positive
      (PPD, Siebert purified protein derivative of tuberculin; DTHR, delayed type
      hypersensitivity reaction) individuals who had been inoculated with a mixture of
      PPD-cross-linked V3 peptides from five HIV strains and then exhibited declines in
      HIV-1 viremia during the course of vaccination in the absence of combination
      antiretroviral therapy and whose virus levels resurged once vaccine boosting was
      discontinued. RESULTS: Declines in viremia were observed even when the viral V3
      sequences of the patients' HIV differed by at least one or two amino acid
      residues from those of the five peptides in the vaccine. Although viral mutants
      with amino acid substitutions within V3 appeared during vaccination, plasma virus
      loads remained at low levels for several months after these variants appeared.
      About a year after boosting was discontinued, anti-V3 peptide antibodies in the
      patients had declined and plasma virus returned to the prevaccination levels or
      higher. Compared with the isolates that predominated during the course of
      vaccination, the resurgent viruses contained zero to six amino acid residue
      differences in the V3 loop but few synonymous substitutions. CONCLUSIONS: Viruses
      with altered V3 sequences did emerge but did not result in increased viremia
      during the course of vaccination. In two individuals where V3 mutations were
      absent in the virus that re-emerged after vaccine boosting ceased, resurgence
      could not have been a consequence of V3 changes.

PMID- 11316995
TI  - Dose-escalation, phase I/II study of azithromycin and pyrimethamine for the
      treatment of toxoplasmic encephalitis in AIDS.
AB  - OBJECTIVE: To assess the safety, tolerance and activity of increasing doses of
      azithromycin in combination with pyrimethamine for the treatment of toxoplasmic
      encephalitis (TE) in patients with AIDS. DESIGN: A phase I/II dose-escalation
      study of oral azithromycin in combination with pyrimethamine. SETTING: Eight
      clinical sites in the United States. PATIENTS: Forty-two adult HIV-infected
      patients with confirmed or presumed acute TE. METHODS: Patients were enrolled
      into three successive cohorts receiving azithromycin 900, 1200 and 1500 mg a day
      with pyrimethamine as induction therapy. The induction period was 6 weeks
      followed by 24 weeks of maintenance therapy. MAIN OUTCOME MEASURES: Patient
      response was evaluated clinically and radiologically. RESULTS: Of the 30
      evaluable patients, 20 (67%) responded to therapy during the induction period.
      Ten experienced disease progression. Of the 15 patients who received maintenance
      therapy, seven (47%) relapsed. Six patients discontinued treatment during the
      induction period as a result of reversible toxicities. Treatment-terminating
      adverse events occurred most frequently among the patients receiving the 1500 mg
      dose. CONCLUSION: The combination of azithromycin (900-1200 mg a day) and
      pyrimethamine may be useful as an alternative therapy for TE among patients
      intolerant of sulfonamides and clindamycin, but maintenance therapy with this
      combination was associated with a high relapse rate. The combination was safe,
      but low-grade adverse events were common.

PMID- 11316996
TI  - Timing of antiretroviral therapy. Use of Markov modeling and decision analysis to
      evaluate the long-term implications of therapy.
AB  - BACKGROUND: The timing of initiation of antiretroviral therapy is controversial.
      Current guidelines are heavily based on the principle of 'hit early, hit hard',
      although the long-term implications of this approach are unknown. METHODS: Using
      Markov modeling and decision analysis we modeled the virologic outcomes over 10
      years in a hypothetical population of 10 000 HIV-infected patients in which
      therapy (with the possibility of three sequential regimens before the development
      of multidrug-resistant virus) is started immediately versus starting
      progressively at rates of 5, 10, 15, 20 or 30% of the original population each
      year. The model used inputs from available clinical trial data: virologic success
      rate and durability of the response of the first and subsequent regimens. We
      performed one-way and two-way sensitivity analysis to evaluate changes in the
      input variables. RESULTS: If therapy is started immediately in all patients, by
      10 years 57% would be undetectable, but 38% would have detectable multidrug
      resistant virus. In contrast, the population as a whole would have had better
      virologic outcomes if one waited before starting treatment at any progression
      rate; for example, initiating therapy in 10% of the subjects per year results in
      64% of patients being undetectable and 24% with multidrug-resistant virus. Two
      way sensitivity analysis demonstrates that immediate initiation should be at
      least 15 to 20% better than delayed antiretroviral therapy to justify immediate
      initiation of therapy over a wide range of success rates of the delayed start.
      CONCLUSION: Our analysis, utilizing optimistic outcomes based on short-term
      clinical trials, provides a theoretical basis for questioning the current
      aggressive early use of therapy and should help prompt studies that look at when
      and how to start antiretroviral therapy.

PMID- 11316997
TI  - HIV protease and reverse transcriptase variation and therapy outcome in
      antiretroviral-naive individuals from a large North American cohort.
AB  - OBJECTIVE: To assess the effect of baseline HIV reverse transcriptase (RT) and
      protease sequence variation on virologic outcomes in a large cohort of
      antiretroviral-naive patients in British Columbia, Canada. METHODS: Population
      sequencing of RT and protease was performed on baseline viral RNA of all
      antiretroviral-naive patients first seeking treatment in British Columbia between
      June 1997 and August 1998 (n = 479). Relative risks of virological failure
      associated with genotypic differences from a 'standard' HIV strain (HXB2) were
      assessed for up to 18 months. RESULTS: The prevalence of key baseline mutations
      known to confer resistance to RT and protease inhibitors (PI) was 3.4 and 3.8%,
      respectively. No statistically significant impact on virologic outcomes could be
      established for these patients. However, the data suggest that some individuals
      (harboring a M184V mutation in RT or a V82I in protease) may have benefited from
      pre-therapy resistance tests. 'Secondary' mutations in the protease associated
      with resistance (e.g. codons 10, 36 or 63) were common, but the presence of these
      secondary mutations, either alone or in combination, did not appear to result in
      early loss of therapeutic virological suppression. Preliminary analyses suggest
      that an amino acid change at codon 35 in the protease may be associated with
      early treatment failure. CONCLUSIONS: The results suggest that routine genotyping
      of naive patients about to start antiretroviral therapy would be of benefit to a
      relatively small proportion of the population. Secondary mutations associated
      with resistance to PI alone were not found to affect virologic outcomes
      significantly.

PMID- 11316998
TI  - Sequencing of protease inhibitor therapy: insights from an analysis of HIV
      phenotypic resistance in patients failing protease inhibitors.
AB  - OBJECTIVE: To characterize the pattern of HIV-1 susceptibility to protease
      inhibitors in patients failing an initial protease inhibitor-containing regimen.
      DESIGN: A cross-sectional analysis of antiretroviral susceptibility. SETTING: HIV
      clinics in six metropolitan areas. PATIENTS: Eighty-eight HIV-infected adults
      with HIV RNA > 400 copies/ml after > or = 6 months of antiretroviral therapy,
      including the use of one protease inhibitor for > or = 3 months. MEASUREMENTS:
      The frequency and magnitude of decreased susceptibility, measured with a
      phenotypic assay using recombinant constructs, to five protease inhibitors.
      Decreased susceptibility was defined as > 2.5-fold increase in the 50% inhibitory
      concentration (IC50) compared with drug sensitive control virus. RESULTS: At
      study entry, patients were being treated with nelfinavir (63%), indinavir (25%),
      or another protease inhibitor (11%). HIV isolates from these patients were
      susceptible (fold change < 2.5) to all five protease inhibitors in 18% of
      patients and to none in 8%. Isolates from patients receiving nelfinavir were less
      likely to have reduced susceptibility to other protease inhibitors than isolates
      from patients treated with indinavir (P < 0.001) or one of the other three agents
      (P < 0.001), even after adjustment for the duration of prior protease inhibitor
      use. Reduced susceptibility to saquinavir and amprenavir was observed
      significantly less frequently than for the other protease inhibitors. CONCLUSION:
      The frequency of protease inhibitor cross-resistance and the magnitude of changes
      in susceptibility varied according to the initial protease inhibitor used in the
      failing treatment regimen. Significantly less protease inhibitor cross-resistance
      was demonstrated for isolates from patients failing a nelfinavir-containing
      regimen compared with those from patients receiving other protease inhibitors.

PMID- 11316999
TI  - Incidence of pancreatitis in HIV-infected patients receiving nucleoside reverse
      transcriptase inhibitor drugs.
AB  - BACKGROUND: Pancreatitis is a known adverse effect of the nucleoside reverse
      transcriptase inhibitors, particularly didanosine. Hydroxyurea has been used to
      potentiate the antiviral efficacy of didanosine, but recently there has been
      concern that severe and even fatal pancreatitis may be more likely to occur when
      hydroxyurea is used in combination with didanosine. We investigated the incidence
      of pancreatitis in patients using nucleoside analogues with or without
      hydroxyurea. METHODS: Data were obtained from patients followed longitudinally on
      the Johns Hopkins HIV Clinic. Incidence rates of pancreatitis were calculated for
      each antiretroviral regimen that included zidovudine, stavudine, didanosine (+
      hydroxyurea), and didanosine + stavudine (+ hydroxyurea). Poisson regression was
      used to compare the relative rate of pancreatitis for each regimen adjusting for
      other covariates. RESULTS: A total of 2613 patients received at least one of the
      nucleoside reverse transcriptase inhibitor-containing regimens. There were 33
      cases of pancreatitis. The crude incidence rate of pancreatitis ranged from 0.18
      cases per 100 person-years on therapy for zidovudine to 6.25 cases per 100 person
      years for didanosine + hydroxyurea. Compared to didanosine alone, and adjusting
      for CD4 cell count and other variables, the relative risk (RR) of pancreatitis
      was 8.56 [95% confidence interval) CI, 1.85-35.59] for didanosine + hydroxyurea,
      and 2.35 (95% CI, 0.46-11.89) for didanosine + stavudine + hydroxyurea. For any
      use of hydroxyurea, the RR = 4.01 (95% CI, 1.02-15.89). Other risk factors for
      pancreatitis included a CD4 cell count < 200 x 106 cells/l, female sex, and a
      history of pancreatitis. CONCLUSIONS: Our data show that the risk of pancreatitis
      is four-fold higher when hydroxyurea is used. The use of hydroxyurea with
      didanosine should probably be discouraged if other treatment options are
      available.

PMID- 11317001
TI  - Decreasing rates of Kaposi's sarcoma and non-Hodgkin's lymphoma in the era of
      potent combination anti-retroviral therapy.
AB  - OBJECTIVE: To describe the changing incidence of Kaposi's sarcoma (KS) and non
      Hodgkin's lymphoma (NHL) in people with HIV in Australia during the time period
      of introduction of potent combination anti-retroviral therapy. DESIGN: A
      national, population-based linkage study of cancer and HIV registration data.
      METHODS: We calculated person-year rates of KS and NHL in people after reporting
      of HIV diagnosis. Trends in cancer incidence rates were examined, based on four
      time periods defined by the availability of specific anti-retroviral therapies.
      RESULTS: Linkage identified 206 cases of KS and 235 cases of NHL in 8108 people
      reported with HIV infection. There was an increasing trend in NHL incidence rates
      over the four time periods (P for trend, 0.012), but incidence for the period
      since the availability of the new therapies was significantly lower than that for
      the period immediately prior (incidence rate ratio 0.58; 95% confidence interval,
      0.36-0.92). Incidence of KS had been decreasing prior to the new therapies and
      declined further since their widespread use (P for trend, 0.045). CONCLUSIONS:
      Population-based incidence rates of AIDS related KS and NHL have decreased since
      the widespread use of potent anti-retroviral therapies in Australia. NHL
      incidence decreased less than KS, and NHL is now the most common AIDS-associated
      cancer in Australia.

PMID- 11317000
TI  - Viral burden in genital secretions determines male-to-female sexual transmission
      of HIV-1: a probabilistic empiric model.
AB  - OBJECTIVE: To develop a model to predict transmission of HIV-1 from men to women.
      DESIGN: HIV-1 in seminal plasma, and endocervical CCR5 receptors were correlated
      with epidemiological studies of HIV-1 transmission to develop a probabilistic
      model. SETTINGS: Semen samples were collected from patient subjects in Seattle
      Washington, Chapel Hill, North Carolina, and St. Gallen, Switzerland.
      Endocervical biopsy specimens were obtained from women in Chicago, Illinois.
      PARTICIPANTS: Eighty-six men (not receiving antiretroviral therapy) in whom CD4
      cell count and semen volume were available, and 24 women in whom the number of
      endocervical CCR5 receptors were determined. MAIN OUTCOME MEASURES: Prediction of
      transmission of HIV-1 from men to women per episode of vaginal intercourse based
      on the absolute burden of HIV (volume x HIV RNA copies/ml seminal plasma).
      RESULTS: The model suggests efficient heterosexual transmission of HIV-1 when
      semen viral burden is high. When semen contains 100 000 copies of non-syncytium
      inducing (NSI) HIV RNA the probability of HIV-1 transmission is 1 per 100
      episodes of intercourse; conversely, with 1000 copies NSI HIV RNA in semen,
      transmission probability is 3 per 10 000 episodes of intercourse. CONCLUSIONS:
      This model links biological and epidemiological data related to heterosexual HIV
      1 transmission. The model can be used to estimate transmission of HIV from men
      with high semen viral burden from inflammation, or reduced burden after
      antiretroviral therapy. The results offer a biological explanation for the
      magnitude of the HIV epidemic in places where earlier studies have shown men have
      high semen viral burden, such as in sub-Saharan Africa. The model can be used to
      develop and test HIV-1 prevention strategies.

PMID- 11317002
TI  - Vitamin A and risk of HIV-1 seroconversion among Kenyan men with genital ulcers.
AB  - BACKGROUND: Vitamin A is involved in normal immune function and the maintenance
      of mucosal integrity through complex effects on cellular differentiation.
      OBJECTIVE: We sought to determine whether serum vitamin A levels were associated
      with altered susceptibility to primary infection with HIV-1 in men with high-risk
      sexual behaviour and genital ulcers who presented for treatment at an STD clinic
      in Nairobi, Kenya. METHODS: HIV-1 seronegative men were prospectively followed.
      Vitamin A levels at study entry were compared among 38 men who HIV-1
      seroconverted versus 94 controls who remained HIV seronegative. RESULTS: Vitamin
      A deficiency (retinol less than 20 microg/dl) was very common and was present in
      50% of HIV-1 seroconverters versus 76% of persistent seronegatives.
      Seroconversion was independently associated with a retinol level greater than 20
      microg/dl (HR 2.43, 95% CI 1.25-4.70, P = 0.009), and a genital ulcer aetiology
      caused by Haemophilus ducreyi (HR 3.49, 95% CI 1.03-11.67, P = 0.04).
      Circumcision was independently associated with protection (HR 0.46, 95% CI 0.23
      0.93, P = 0.03). CONCLUSION: Vitamin A deficiency was not associated with an
      increased risk of HIV-1 infection among men with concurrent STD. A decreased risk
      of HIV-1 seroconversion was independently associated with lower retinol levels.
      The effects of vitamin A on macrophage and lymphoid cell differentiation may
      paradoxically increase mucosal susceptibility to HIV-1 in some vulnerable
      individuals, such as men with genital ulcers. Lack of circumcision and chancroid
      are confirmed as important co-factors for heterosexual HIV-1 transmission. The
      role of vitamin A in heterosexual HIV-1 transmission requires further study.

PMID- 11317003
TI  - Measuring the risk of HIV transmission.

PMID- 11317004
TI  - Risk of recurrent non-typhoid Salmonella bacteraemia after early discontinuation
      of ciprofloxacin as secondary prophylaxis in AIDS patients in the era of highly
      active antiretroviral therapy.

PMID- 11317005
TI  - Prevalence of HIV-1 drug resistance in antiretroviral-naive patients: a
      prospective study.

PMID- 11317006
TI  - Incidence of HIV infection among gay men in a London HIV testing clinic, 1997
      1998.

PMID- 11317007
TI  - Are HIV-infected women who breastfeed at increased risk of mortality?

PMID- 11317008
TI  - Where does free infective HIV-1 rebound come from?

PMID- 11317009
TI  - Long-term reduction of HIV transmission from mother to breastfed child by
      antiretroviral agents: are more drugs better than less?

PMID- 11317010
TI  - A new CX3 CR1 genotype with implications for HIV disease progression.

PMID- 11317011
TI  - Effect of IL-2 therapy on plasma hepatitis C virus-RNA levels in HIV/hepatitis C
      virus co-infected patients.

PMID- 11317012
TI  - ABT 378/r: a novel inhibitor of HIV-1 protease in haemodialysis.

PMID- 11317014
TI  - Staging and managing lung tumors using F-18 FDG coincidence detection.
AB  - PURPOSE: Fluorine-18 fluorodeoxyglucose (F-18 FDG) positron emission tomographic
      (PET) imaging can be a vital tool in the evaluation and preoperative staging of
      pulmonary neoplasms. Imaging studies on the gamma camera using coincidence PET
      (co-PET) were introduced recently into clinical practice. This prospective study
      assessed the efficacy of co-PET for identifying primary tumors, mediastinal lymph
      node involvement, the presence of distant spread, the effect on disease staging,
      and influence on disease management. PATIENTS AND METHODS: Sixty consecutive
      patients with 61 lung tumors were enrolled in the study (36 men, 24 women; age
      range, 32-87 years; mean age, 67 years). Histopathologic confirmation was
      obtained in 58 patients (59 tumors). RESULTS: In assessments of a primary lesion
      to establish its malignant or benign nature, the sensitivity rate of co-PET was
      96% (53 of 55 lesions), the specificity rate was 83% (5 of 6 lesions), and the
      accuracy rate was 95% (58 of 61 lesions). In the co-PET assessment of lymph node
      involvement in which histopathologic confirmation was obtained (n = 32), the
      sensitivity rate was 89% (8 of 9 lesions), the specificity rate was 91% (21 of 23
      lesions), and the accuracy rate was 91% (29 of 32 lesions). Previously unknown
      distant metastases were correctly identified in eight patients, but five false
      positive lesions were detected in the brain. Disease staging was correctly
      altered in 20 patients (33%), and disease management plans were changed in 20
      patients (33%) based on the co-PET findings. Unnecessary surgery was obviated in
      six patients (10%). One patient was given the chance for curative treatment based
      on the findings of the co-PET study. CONCLUSION: The evaluation of patients with
      lung neoplasms using F-18 FDG coincidence detection appears to be reliable.

PMID- 11317015
TI  - Methotrexate osteopathy demonstrated by Technetium-99m HDP bone scintigraphy.
AB  - The authors report a case of methotrexate osteopathy as revealed by Tc-99m HDP
      bone scintigraphy in a patient with rheumatoid arthritis. Methotrexate is used
      widely in high doses as a chemotherapeutic agent. Lower doses are given in
      rheumatoid and psoriatric arthritis. Methotrexate affects bone metabolism,
      resulting in methotrexate osteopathy, characterized by osteoporosis, osseus pain,
      and even spontaneous (micro)fractures. Radiographic visualization of
      microfractures is difficult. Tc-99m HDP bone scans have been shown to be very
      sensitive in the visualization of changes in bone metabolism as a result of
      methotrexate osteopathy.

PMID- 11317016
TI  - Recombinant human thyroid-stimulating hormone-aided scintigraphy: comparison of
      imaging at multiple times after I-131 administration.
AB  - PURPOSE: Recombinant human thyroid-stimulating hormone (rhTSH) may be used in
      lieu of thyroid hormone withdrawal for the evaluation of thyroid cancer.
      Scintigraphy using the existing rhTSH protocol is performed 48 hours after I-131
      administration. The authors investigated the feasibility of whole-body imaging at
      72 hours and evaluated thyroid tissue uptake at 48 to 144 hours. METHODS: Thirty
      two patients who previously had thyroidectomy for thyroid cancer were examined.
      Whole-body imaging was performed routinely at 48 and 72 hours after I-131
      administration. Thyroid tissue was visualized in 12 patients, and large foci were
      imaged for as long as 144 hours. Activity ratios for thyroid tissue to background
      were determined for 10 patients. RESULTS: Whole-body images at 48 and 72 hours
      were comparable, generally with lower background activity at 72 hours, and
      thyroid tissue was well visualized at all times after 48 hours. Thyroid tissue-to
      background activity ratios at 72 to 144 hours were equal to or greater than those
      at 48 hours in 9 of 10 patients. CONCLUSIONS: Recombinant human TSH-aided whole
      body scintigraphy is possible 72 hours after I-131 administration, adding
      flexibility and convenience to the existing protocol and permitting confirmation
      of findings at 48 hours. Tracer uptake in thyroid tissue persists at later times.
      Therefore, rapid clearance of background activity appears to be the primary cause
      of the previously reported decrease in radioiodine retention in euthyroid persons
      receiving rhTSH.

PMID- 11317017
TI  - Metastatic thyroid cancer occurring as an unknown primary lesion: the role of F
      18 FDG positron emission tomography.
AB  - Thyroid cancer can appear as metastatic disease of an unknown primary origin, and
      fluorine-18 fluorodeoxyglucose (F-18 FDG) positron emission tomographic (PET)
      studies are helpful in the workup evaluation of these patients. The authors
      describe two patients who had metastatic disease from an unknown primary lesion.
      F-18 FDG PET studies played an important role in localizing the primary malignant
      site in the thyroid gland. The utility of F-18 FDG imaging in decreasing the
      number of procedures, cost, and inconvenience to patients is shown clearly in
      both cases.

PMID- 11317018
TI  - Subacute thyroiditis in a single lobe.
AB  - A 33-year-old woman with no history of thyroid disease reported pain in her neck
      and a sore throat. On physical examination, the thyroid gland was palpable. Serum
      T3 and T4 levels were increased, and the thyroid-stimulating hormone level was
      decreased. Thyroid scintigraphy with Tc-99m pertechnetate revealed
      nonvisualization of the left lobe of the thyroid. Ultrasonographic examination
      confirmed the presence of the left thyroid lobe. Fine-needle aspiration biopsy
      revealed thyroiditis of the left lobe of the thyroid. The patient was started on
      an anti-inflammatory drug. The follow-up thyroid scan showed a normal thyroid
      gland.

PMID- 11317019
TI  - Detection of cranial metastases by F-18 FDG positron emission tomography.
AB  - Fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) scanning
      has been useful in the management of various cancers. The normal glucose use of
      gray matter often limits the detection of metastatic lesions to the brain and
      skull with FDG PET. The authors report two cases of calvarial metastases: one
      with pheochromocytoma and the other with non-small-cell lung carcinoma. These
      cases illustrate the crucial role that FDG PET can play when patients are
      examined for metastases. The important concept of contrast resolution that is
      achieved with PET imaging is discussed as an advantage that significantly
      overcomes its limited spatial resolution in detecting small lesions that may not
      be detected by anatomic imaging techniques with high spatial resolution.

PMID- 11317020
TI  - Can preoperative lymphoscintigraphy be used as a guide in treatment planning of
      breast cancer?
AB  - PURPOSE: The purpose of this study was to map the lymphatic drainage patterns of
      breast cancer with lymphoscintigraphy to evaluate the variability of drainage and
      to determine whether lymphatic mapping can help to increase the certainty of
      breast cancer staging. MATERIALS AND METHODS: Fifty women with breast cancer
      (mean age, 49 years) were included in the study. Lymphoscintigraphy was performed
      with 1 mCi Tc-99m rhenium sulfide colloid in a 2-ml volume injected into the four
      quadrants of the peritumoral area using a 25-gauge needle. Ten-minute dynamic
      images and 2-hour delayed static images were obtained in the anterior and lateral
      positions using a gamma camera with a high-resolution collimator. All patients
      had a modified radical mastectomy and axillary dissection. The results were
      evaluated with histopathologic findings of the axilla. RESULTS: Six patients had
      excision biopsies before surgery. Of 13 patients with centrally located tumors,
      84% had axillary lymphatic drainage, whereas 53% drained to internal mammary
      lymphatics. Of 23 patients with outer quadrant tumors, 4 showed no lymphatic
      drainage and all of them had metastatic tumor in the axillary lymph nodes.
      Axillary drainage was seen in 82% of patients and internal mammary lymphatic
      drainage in 23%. Of eight patients with inner quadrant tumors, one patient with
      no lymphatic drainage was found to have metastases in the axilla. In this group,
      62% had axillary and 50% had internal mammary lymphatic drainage, and one patient
      had supraclavicular drainage. CONCLUSIONS: Lymphoscintigraphy indicates that
      drainage routes may vary, and thus it may play a guiding role in patients with
      breast cancer who need radiotherapy. In patients with internal mammary lymphatic
      drainage, the accuracy of radiotherapy planning may increase if internal mammary
      lymphoscintigraphy is added to the protocol. In patients with internal mammary
      drainage, obtaining an internal mammary lymphatic biopsy during surgery will also
      increase the accuracy of staging.

PMID- 11317021
TI  - A normal variant on Tl-201 and Tc-99m MIBI whole-body imaging: the superior right
      atrial wall (auricle) and superoanterior right ventricular wall are often seen as
      mediastinal lesions.
AB  - PURPOSE: The authors have often observed on Tl-201 and Tc-99m sestamibi (MIBI)
      scans in patients with thyroid cancer a small focus of increased uptake in the
      right midparasternal region (focus A) or sometimes in the lower mid chest at the
      level of the lower sternum (focus B) just inferomedial to focus A. The objective
      of this study was to assess the frequency of this finding on Tl-201 MIBI studies,
      to assess the incidence of true pathologic lesions corresponding to these foci,
      and to identify their nature. MATERIALS AND METHODS: One hundred ten whole body
      Tl-201 studies using 4 mCi (148 MBq) and 84 MIBI studies using 20 mCi (740 MBq:
      first-pass, planar, and SPECT images) were reviewed. The appearance of either
      focus A or focus B on three orthogonal SPECT images was correlated with an atlas
      of cross-sectional anatomy and computed tomography. If focus A was seen on the
      immediate static image (obtained at the end of the first-pass acquisition without
      moving the patient), this image was coregistered with a selected image from the
      first-pass study showing the superior vena cava and also with another selected
      image showing the ascending aorta. RESULTS: Focus A was seen in 40% of Tl-201
      scans and in 49% of MIBI scans, whereas focus B was seen in 20% of Tl-201 scans
      and 39% of MIBI scans. On correlation of the SPECT images with a cross-sectional
      anatomy atlas, focus A and focus B invariably corresponded to the superior
      portion of the right auricle and basal superoanterior right ventricular wall,
      respectively. These myocardial regions are prominent and sometimes appear as
      discrete foci because they are considerably thicker than other parts of the right
      atrial and right ventricular muscle, respectively, and because they are seen
      partly end-on in the anterior projection. CONCLUSIONS: The superior portion of
      the right auricle and basal superoanterior right ventricular myocardium often
      appear as isolated foci on whole-body Tl-201 and MIBl scans. Neither focus should
      be interpreted as a metastatic lesion in patients with possible cancer or as an
      ectopic parathyroid adenoma in patients with hyperparathyroid disease.

PMID- 11317022
TI  - Assessment of viable splenic tissue in massive splenic infarction with a Tc-99m
      heat-damaged RBC scan.
AB  - A 59-year-old man with essential thrombocytosis was examined for abdominal pain.
      Splenic infarction was diagnosed on a computed tomographic scan. The Tc-99m heat
      denatured RBC scan showed viable splenic tissue that was not evident on the
      computed tomographic scan or Tc-99m sulfur colloid scintigraphy.

PMID- 11317023
TI  - Follow-up of acute pyelonephritis in children by Tc-99m DMSA scintigraphy:
      quantitative and qualitative assessment.
AB  - PURPOSE: The author's goal was to create a system to identify children at risk
      for development of progressive renal damage. METHODS: Thirty-four children were
      examined with Tc-99m DMSA scintigraphy in the acute stage of an initial episode
      of pyelonephritis, after 6 months, and again after 1 year. The scintigraphic
      findings were correlated with clinical and laboratory data. RESULTS: All children
      had parenchymal defects in the acute stage: 93% of the kidneys and 85%
      bilaterally. After 6 months, the defects had diminished or disappeared in 66% of
      the kidneys. New defects appeared in 22%. At 1 year, no further improvement was
      seen in the kidneys, with an improved or unchanged pattern at 6 months. New
      defects appeared in 34%. Mean kidney activity uptake expressed as the percentage
      of administered dose (KU/AD), was low in the acute stage, increased at 6 months,
      with no further significant increase at 1 year. Eighty-three percent of children
      with urine cultures growing > or = 104 bacteria/ml at follow-up had decreased
      KU/AD values, whereas all children with urine cultures growing < 104 bacteria/ml
      had increased KU/AD values. CONCLUSIONS: Quantitative assessment increases the
      sensitivity of Tc-99m DMSA scintigraphy. Follow-up with this method makes it
      possible to identify the children with decreasing renal tubular function who may
      be at risk for progressive renal damage. Moderate bacteruria of 104 bacteria/ml
      urine is associated with deterioration of renal tubular function.

PMID- 11317024
TI  - Potential uses of computed tomography-SPECT and computed tomography-coincidence
      fusion images of the chest.
AB  - The ability to fuse (or merge) data sets from SPECT and coincidence nuclear
      medicine scans with computed tomographic images combines physiologic information
      from the former method with the superior anatomic resolution of the latter
      technique. In many cases, this allows more definitive diagnosis than can be
      obtained by simple visual comparison of nuclear medicine images and conventional
      cross-sectional imaging. The technique may be used in the staging and follow-up
      of lung carcinoma, pulmonary carcinoid, and lymphoma. It may also aid in the
      interpretation of perfusion defects in Tc-99m MAA lung scanning, aid in the
      interpretation of ground-glass opacity in selected cases of chest high-resolution
      computed tomography, and aid in the diagnosis of some mediastinal masses (e.g.,
      intrathoracic goiters). In this nuclear medicine atlas, the method used to create
      fusion images in the chest is described, and examples of fusion imaging with
      radiopharmaceuticals are given that may be of clinical use in chest disease.

PMID- 11317025
TI  - Bone scan findings of combined gout and septic arthritis in the same digit.

PMID- 11317026
TI  - Shoulder anatomy defined by a Tc-99m leukocyte study.

PMID- 11317027
TI  - Detection of an artifact on lumbar SPECT.

PMID- 11317028
TI  - Best diagnostic method for floating kidney is sequential bone scintigraphy with
      the patient in the supine and upright positions.

PMID- 11317029
TI  - A rare case of cervical vertebral body osteoid osteoma.

PMID- 11317030
TI  - Sternocostoclavicular hyperostosis: scintigraphic evaluation.

PMID- 11317031
TI  - Unexpected myocardial uptake on bone scintigraphy in an infant with Kawasaki
      disease.

PMID- 11317032
TI  - Abnormal upper body soft tissue uptake on skeletal scintigraphy: a sign of
      superior vena cava obstruction.

PMID- 11317033
TI  - Intense F-18 fluorodeoxyglucose uptake caused by mycobacterium avium
      intracellulare infection.

PMID- 11317034
TI  - A motion artifact on a gastrointestinal bleeding scan mimicking a second axillary
      femoral arterial bypass graft.

PMID- 11317035
TI  - False-positive F-18 FDG gamma camera positron emission tomographic imaging
      resulting from inflammation of an anterior mediastinal mass in a patient with non
      Hodgkin's lymphoma.

PMID- 11317036
TI  - Primary breast lymphoma detected with Tc-99m tetrofosmin scintigraphy.

PMID- 11317037
TI  - A case of malignant lymphoma with testis involvement detected by Ga-67 scan.

PMID- 11317038
TI  - A case of secondary amyloidosis with calcium deposition in the liver.

PMID- 11317039
TI  - Hepatic cysts detected on myocardial perfusion scintigraphy.

PMID- 11317040
TI  - Failure to detect a huge Meckel's diverticulum with abundant ectopic gastric
      mucosa on gastric mucosal scintigraphy with Tc-99m pertechnetate.

PMID- 11317041
TI  - Tc-99m MDP and Ga-67 citrate scintigraphic findings in sarcoidosis with osseous
      involvement.

PMID- 11317042
TI  - Pseudoneuroblastoma demonstrated by I-123 MIBG SPECT.

PMID- 11317043
TI  - Intracranial meningioma with abnormal accumulation of Tc-99m MDP on bone
      scintigraphy: different intensities between reactive hyperostosis and tumor
      calcification.

PMID- 11317044
TI  - Colonic visualization during renal scintigraphy secondary to
      ureterosigmoidostomy.

PMID- 11317045
TI  - Unilateral diaphragmatic crus uptake on FDG positron emission tomographic
      imaging.

PMID- 11317046
TI  - Reduced F-18 FDG uptake with marrow may predict photopenia of corresponding
      vertebrae on bone scintigraphy.

PMID- 11317048
TI  - Newer modes of mechanical ventilation for the neonate.
AB  - For decades, the overwhelming majority of infants requiring mechanical
      ventilation for respiratory failure were treated with standard time-cycled,
      pressure-limited intermittent mandatory ventilation. Technologic advances in the
      1990s brought forth sophisticated transducers and microprocessor-based mechanical
      ventilators that enabled implementation of many newer modes of mechanical
      ventilation. Some of these are volume-targeted rather than pressure-targeted, and
      many allow an element of patient control of the ventilator, including initiation
      and termination of inspiration and control of flow. Some modes are even hybrids,
      combining the best features of both pressure-targeted and volume-targeted modes.
      This article reviews the principles and salient clinical features of the newer
      ventilatory modes for newborns with respiratory failure.

PMID- 11317049
TI  - Outcomes of neonates with congenital heart disease.
AB  - One of the most important advances of the past 10 to 15 years in the field of
      pediatric cardiology is the improvement in prognosis for neonates with complex
      congenital heart disease. During the past 18 months, several publications have
      addressed outcomes in neonates with congenital heart disease. Many of these
      reports demonstrate continuing improvement in preoperative, early postoperative,
      and late postoperative survival among patients with complex neonatal heart
      defects. Other reports shed substantial new light on late functional outcome,
      especially neurodevelopmental status. In addition to data on survival, morbidity,
      and functional status, we discuss developments in perioperative evaluation and
      management that are likely to further the trend toward improved outcome for
      neonates with complex congenital heart disease.

PMID- 11317050
TI  - New concepts in necrotizing enterocolitis.
AB  - Necrotizing enterocolitis is an overwhelming gastrointestinal emergency that
      primarily afflicts premature infants born weighing less than 1500 g. Despite
      years of investigation, the etiology remains unclear, and accepted prevention and
      treatment strategies are lacking. Studies published over the last year have
      provided new insight into several aspects of this complex disease. In this
      review, novel information is presented on (1) the epidemiology; (2) methods of
      early diagnosis, such as abdominal magnetic resonance imaging; (3) the importance
      of risk factors, including assessment of feeding strategies and role of bacterial
      colonization; (4) the pathophysiology, highlighting experimental and clinical
      trials evaluating the role of inflammatory mediators and growth factors on the
      disease; (5) preventive strategies, such as anaerobic bacterial supplementation;
      and (6) surgical interventions, including peritoneal drainage. Understanding some
      of these important aspects of necrotizing enterocolitis may help improve the
      outlook of patients with this dreaded disease. Although the incidence of neonatal
      necrotizing enterocolitis (NEC) and the mortality stemming from this disease have
      not significantly improved over the last 30 years, there is exciting new
      information that may significantly improve the outlook of patients with this
      overwhelming intestinal emergency in the near future.

PMID- 11317051
TI  - Controversies in the diagnosis and management of hypotension in the newborn
      infant.
AB  - Although close to half of the newborns admitted to neonatal intensive care units
      receive treatment for "hypotension," the normal physiologic blood pressure range
      ensuring appropriate organ perfusion in the neonate is unknown. Thus, the
      decision to treat hypotension in the newborn is based on statistically defined
      gestational and postnatal age-dependent normative blood pressure values and
      physicians' beliefs rather than on data bearing physiologic reference. Dopamine
      is the most widely used sympathomimetic amine in the treatment of neonatal
      hypotension, and it is more effective than dobutamine in raising blood pressure.
      Volume administration is less effective in the immediate postnatal period, and
      its extensive use is associated with significant untoward effects, especially in
      preterm infants. During the course of their disease, some of the sickest
      hypotensive newborns become unresponsive to volume and pressor administration.
      This phenomenon is caused by the desensitization of the cardiovascular system to
      catecholamines by the critical illness and relative or absolute adrenal
      insufficiency. The findings that steroids rapidly up-regulate cardiovascular
      adrenergic receptor expression and serve as hormone substitution in cases of
      adrenal insufficiency explain their effectiveness in stabilizing the
      cardiovascular status and decreasing the requirement for pressor support in the
      critically ill newborn with volume-and pressor-resistant hypotension. Finally,
      despite recent advances in our understanding of the pathophysiology and
      management of neonatal hypotension, there are few data on the impact of the
      treatment on organ blood flow and tissue perfusion and on neonatal morbidity and
      mortality.

PMID- 11317052
TI  - Prevention of bronchopulmonary dysplasia.
AB  - The clinical syndrome of bronchopulmonary dysplasia (BPD) in preterm infants
      results primarily from an arrest of lung vascular and alveolar development. The
      most likely mediators are proinflammatory cytokines that are induced by antenatal
      exposure to infection, postnatal ventilation, and oxygen exposure. New
      epidemiologic data suggest that attempts to avoid intubation and ventilation are
      the best ways to avoid severe BPD. The claim that one ventilation technique is
      better than another remains unconvincing, and any strategy that maintains the
      lung open and minimizes tidal volumes probably will be helpful. More adverse
      effects of postnatal steroids are being recognized. New insights into the
      pathophysiology of BPD and a new emphasis on minimizing ventilation and
      ventilator-mediated injury should improve outcomes for very preterm infants.

PMID- 11317054
TI  - Ambulatory blood pressure measurements.
AB  - Ambulatory blood pressure monitoring (ABPM) has emerged as a valuable clinical
      and research tool in the assessment of pediatric hypertension. Large databases of
      24-hour blood pressure monitorings in healthy children are under development for
      establishing normal reference values analogous to the Task Force data for casual
      blood pressure. In the clinical setting, pediatric studies using ABPM to evaluate
      elevated blood pressure have shown that the prevalence of white coat hypertension
      in children is similar to that reported in adults. Furthermore, 24-hour blood
      pressure parameters are correlated with hypertensive end-organ injury such as
      left ventricular hypertrophy. ABPM has allowed detailed assessment of circadian
      blood pressure patterns that show early subtle abnormalities in some high-risk
      groups and normal patterns in other groups previously thought to be at high risk.
      These studies will assist in the practice of evidence-based medicine regarding
      pediatric hypertension that will improve the long-term care that pediatricians
      provide to their patients.

PMID- 11317055
TI  - Prenatal hydronephrosis.
AB  - Prenatal hydronephrosis is diagnosed with an incidence of 1:100 to 1:500 maternal
      fetal ultrasonographic studies. Although ultrasonography accurately describes
      dilation of the renal collecting system, it cannot define mechanical obstruction,
      a functional characteristic. The purpose of prenatal screening has changed from
      simple detection of hydronephrosis to selection for specific diagnosis-based
      management. The natural history of prenatal hydronephrosis is difficult to
      determine, and therefore physicians who take care of the fetus and infant are
      challenged with the following question: when does dilation of the renal
      collecting system indicate that serious pathology (ongoing renal deterioration)
      exists? The diagnosis of prenatal hydronephrosis, indications for and timing of
      prenatal intervention, and recommendations for treating children with a history
      of prenatal hydronephrosis are included in this review.

PMID- 11317056
TI  - Ion channels in disease.
AB  - Diseases as different as cardiac arrhythmias, epilepsy, myotonia, malignant
      hyperthermia, familial hyperinsulinism, and Bartter syndrome have all been linked
      to mutations in genes encoding ion channels. This has been made possible by an
      exciting and fruitful collaboration between clinicians, geneticists, and
      physiologists. It has led to a more detailed understanding not only of pathology
      but also of physiology, as the deficiency of a certain gene helps unravel its
      physiologic role. Some exciting and surprising findings have recently been made
      in the field of "channelopathies." Understanding these diseases on the molecular
      level will provide the basis for a rational therapeutic approach to affected
      patients.

PMID- 11317057
TI  - Case report: Teenage girl with proteinuria and amenorrhea.
AB  - Recent research has advanced the understanding of many diseases to a molecular
      level. Described here is the case of a teenage girl with proteinuria and primary
      amenorrhea. We present the current knowledge of her underlying disorder, Frasier
      syndrome, and its genetic basis, which are specific mutations in the Wilms tumor
      gene. The findings in Frasier syndrome research are contrasted with those of a
      related disorder, Denys-Drash syndrome, which is caused by different mutations in
      the same gene.

PMID- 11317059
TI  - Pediatric poisonings from household products: hydrofluoric acid and methacrylic
      acid.
AB  - Household products continue to be a cause of poisoning morbibidity and mortality.
      Young children frequently are exposed to cleaning products and cosmetics in the
      course of exploring their environment. Most of these exposures are insignificant,
      but some result in death or permanent disability. This review discusses two
      products that have been responsible for serious injury and death in children:
      hydrofluoric acid and methacrylic acid. It also discusses federal initiatives
      designed to protect children from these and other household hazards.

PMID- 11317060
TI  - Herbal medicines for children: an illusion of safety?
AB  - Herbal medicaments are in common use. In general, the judicious use of carefully
      selected and prepared herbal medications seems to cause few adverse effects and
      may be beneficial. However, toxic effects of these products have been reported
      with increasing frequency. Infants and children may be even more susceptible to
      some of the adverse effects and toxicity of these products because of differences
      in physiology, immature metabolic enzyme systems, and dose per body weight.
      Although information promoting the use of herbal medicine is widespread, true
      evidence-based information about the efficacy and safety of herbal medications is
      limited. Although the most conservative approach is to recommend against use of
      herbal medicine until such evidence is available, some patients are not receptive
      to this approach. A reasonable approach for health care providers may be to
      follow such use closely, assist in herbal therapeutic decisions, and monitor for
      adverse effects and interactions. This manuscript discusses general concepts
      about herbal medicines, public health implications, and a framework for
      mechanisms of adverse effects from the use of botanicals. Adverse effects and
      toxicity of selected herbal products, including Chinese herbal medicines, are
      presented. The authors propose a risk reduction approach in which physicians
      actively seek information about the use of complementary or alternative medicine
      while taking medical histories.

PMID- 11317061
TI  - The many faces of ecstasy.
AB  - References to the word ecstasy in popular culture can mean different things to
      different individuals. The most common form of ecstasy (3,4
      methylenedioxymethamphetamine [MDMA]), is an amphetamine with some hallucinogenic
      properties at high doses. It is directly neurotoxic to the human brain and has
      been linked to a number of deaths worldwide. Deaths result from hyperthermia,
      hyponatremia, or cerebral edema. A naturally occurring metabolite of gamma
      aminobutyric acid, gammahydroxybutyrate (GHB) is a potent central nervous system
      depressant. Although GHB is a Schedule I drug, analogs remain widely available
      for consumption. Acute intoxication with GHB or its analogs leads to coma and
      respiratory depression. Chronic use of GHB or its analogs is associated with a
      withdrawal syndrome characterized by autonomic excitation. Herbal ecstasy refers
      to ephedrine-containing preparations. Acute and chronic overdoses of herbal
      ecstasy have been linked to hypertension, tachydysrythmias, myocardial
      infarctions, cerebrovascular accidents, and deaths. There is no regulation of the
      ephedrine content of available herbal ecstasy products.

PMID- 11317062
TI  - Chronic acetaminophen overdosing in children: risk assessment and management.
AB  - Acetaminophen is currently the pediatric analgesic and antipyretic of choice.
      Although children appear to tolerate single, high-dose ingestions well, the
      literature is replete with reports of significant morbidity and mortality after
      repeated supra-therapeutic dosing. Proposed risk factors for injury with chronic
      use include age, total dose, duration, presence of intercurrent febrile illness,
      starvation, co-administration of cytochrome P450-inducing drugs, underlying
      hepatic disease, and unique genetic makeup. Evaluation of these children should
      include serum acetaminophen concentration, prothrombin time, and serum bilirubin
      and transaminase concentrations. The Rumack-Mathew nomogram should not be used to
      estimate the risk of hepatotoxicity in cases of chronic ingestion. Based on
      history, clinical examination, and laboratory findings, patients may be placed in
      three categories: those without hepatic injury and with no residual acetaminophen
      to be metabolized, those without injury but with some acetaminophen to be
      metabolized, and those with hepatotoxicity. Those without injury and no residual
      acetaminophen need not be treated or followed. Patients with hepatotoxicity or
      potential for hepatotoxicity based on residual acetaminophen should be treated
      with N-acetylcysteine. Most importantly, because so many parents are unaware of
      the potential risk of inappropriate dosing, education is the key to preventing
      future cases.

PMID- 11317063
TI  - Rational use of toxicology testing in children.
AB  - The majority of all patients with poison exposures in the United States are
      children. The evaluation and management of poisoned patients may be aided by the
      use of laboratory assays, ranging from basic assessments not uniquely indicated
      for the poisoned patient to highly sophisticated laboratory tests with very
      specific indications. Literature concerning poisoning in pregnant patients is
      evaluated and recommendations regarding the utility of pregnancy testing in
      poisoned females are discussed. Recent studies evaluating the use of toxicology
      testing in pediatrics have concluded that the use of comprehensive toxicology
      screening in pediatric patients is costly and does not affect the medical
      management of most poisoned patients. The utility of focused quantitative serum
      assays to determine serum levels of particular poisons is reviewed. Toxicology
      tests used for detection of drugs of abuse, with a particular focus on the
      capabilities and limitations of such tests, are discussed. The potential pitfalls
      that occur when toxicology tests are obtained indiscriminately, are misapplied,
      or are misunderstood are analyzed. Hair sampling as nonemergent toxicology
      testing for drugs of abuse is discussed.

PMID- 11317065
TI  - Diagnosis and management of attention-deficit/ hyperactivity disorder in
      children.

PMID- 11317066
TI  - Lower respiratory tract infections in children.
AB  - Lower respiratory tract infections-pneumonia, atypical pneumonia, bronchiolitis,
      and bronchitis-are responsible for much morbidity and mortality in the pediatric
      population. On a regular basis, pediatricians clinically diagnose these
      conditions and must make decisions regarding evaluation and treatment. The focus
      of this update is on new developments in the past year in the areas of
      epidemiology, etiology, diagnosis, treatment, and prevention of lower respiratory
      tract infections.

PMID- 11317067
TI  - Sudden infant death syndrome.

PMID- 11317068
TI  - Child abuse and neglect: prevention and intervention.

PMID- 11317069
TI  - Effect of highly active antiretroviral therapy on expression of interleukin-10
      and interleukin-12 in HIV-infected patients.

PMID- 11317070
TI  - Dysregulation of beta-chemokines in the lungs of HIV-1-infected patients.
AB  - The beta-chemokines, macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta,
      monocyte chemotactic protein (MCP)-1 and regulated-on-activation normal T cell,
      expressed and secreted (RANTES) are not only chemotactic for mononuclear cells
      but may be important in suppression of HIV-1 replication through competitive
      binding to the chemokine receptor, CCR5, which is critical to viral entry. In
      this study, bronchoalveolar cells (BACs) and autologous peripheral blood
      mononuclear cells (PBMCs) were obtained from HIV-1-infected participants who did
      not manifest clinical signs of lung disease with peripheral CD4 T-cell count
      >200/mm(3) (n = 7, group with high CD4 count), or CD4 T-cell count <200/mm(3) (n
      = 12, group with low CD4 count), and from healthy study subjects (n = 5). The
      capacity to express beta-chemokines and CCR5 was assessed. Induction of MIP-1
      alpha by lipopolysaccharide (LPS) in BAC of HIV-1-infected study subjects from
      the low CD4 group was less than BAC from healthy study subjects (p <.001), and
      also was less than in BACs from the group with a high CD4 group (p <.001).
      Moreover, the intracellular expression of MIP-1 alpha in LPS-induced monocytes of
      HIV-1-infected patients was significantly less than that from healthy study
      subjects (p <.01). In addition, spontaneous expression of mRNAs for CCR5 and MIP
      1 alpha in BAC was significantly lower in HIV-1-infected patients compared with
      in healthy study subjects (p <.03 and p <.02, respectively). In contrast to the
      findings with MIP-1 alpha, LPS stimulated MCP-1 in BAC from the group of HIV-1
      infected patients with high CD4 count was significantly higher than healthy study
      subjects (p <.001). These dysregulations in the ability to express beta
      chemokines by BAC may be important in the progression of HIV-1 infection in the
      lung.

PMID- 11317071
TI  - Improvement of anemia among HIV-infected injection drug users receiving highly
      active antiretroviral therapy.
AB  - Although anemia is common during HIV infection, it is unclear whether potent
      antiretroviral therapy would improve or worsen anemia. We conducted a study to
      examine the impact of highly active antiretroviral therapy (HAART) on anemia in a
      cohort of HIV-positive injection drug users (IDUs) in Baltimore, Maryland. At
      baseline, the overall prevalence of anemia was 40%. During mean follow-up of one
      year, among 102 subjects who received HAART, there was a mean increase in
      hemoglobin of 3.6 +/- 1.7 g/L (p =.0003) [corrected] and a mean decrease in
      log(10) plasma HIV load of 0.25 +/- 0.06 copies/ml (p <.0002) [corrected]. Among
      103 control subjects who were not receiving antiretroviral medications, there was
      a mean decrease in hemoglobin of 4.2 +/- 1.1 g/L (p <.04) [corrected] and mean
      increase in log(10) plasma HIV load of 0.78 +/- 0.17 copies/ml (p <.0001)
      [corrected]. Multivariate analysis using mixed linear models showed that HAART
      was associated with an increase of hemoglobin of 0.223 g/L per month (p <.0001)
      after adjusting for body mass index, opportunistic infections, and gender. HAART
      was associated with an improvement in anemia, and potential mechanisms that may
      be involved include a reduction in opportunistic infections and the anemia of
      chronic disease and an improvement in nutritional status.

PMID- 11317072
TI  - Qualitative and quantitative PCR measures of cytomegalovirus in patients with
      advanced HIV infection who require transfusions.
AB  - The Viral Activation Transfusion Study (VATS) was a randomized trial that
      compared leukocyte-reduced transfusions with unfiltered red blood cell
      transfusions in HIV and cytomegalovirus (CMV) antibody-positive patients with
      anemia who were undergoing their first blood transfusion. The relations of the
      baseline qualitative and quantitative polymerase chain reaction (PCR) measures of
      plasma CMV viremia, HIV RNA, CD4(+) cell counts, and quality of life in these
      study subjects were examined. The 511 study subjects had a median CD4(+) cell
      count equal to 15 cells/mm3, and 110 (21.5%) had CMV viremia by qualitative
      assay. In multivariate models, frequency of positive qualitative CMV increased
      with decreasing CD4(+) cell counts (p =.04 trend), higher HIV RNA (p <.001), and
      a history of CMV disease (p <.001). Quantitative CMV PCR were performed on the
      110 qualitative assay-positive study subjects. Median CMV viral load was 1780
      copies/ml. In multivariate regression models, lower CD4(+) cell count (p =.03),
      and a history of CMV disease (p <.001) correlated with the level of CMV load. HIV
      RNA load and CMV load were not correlated. A lower Karnofsky score was associated
      with both the presence and quantity of CMV DNA.

PMID- 11317073
TI  - Changing clinical presentation and survival in HIV-associated tuberculosis after
      highly active antiretroviral therapy.
AB  - OBJECTIVE: To assess changes in clinical presentation and outcome of HIV
      associated tuberculosis (TB) before and after widespread implementation of highly
      active antiretroviral therapy (HAART). METHODS: We reviewed clinical charts of
      HIV-infected patients with culture-confirmed pulmonary TB in two referral
      clinical centers in Rome, Italy. The 67 patients diagnosed in 1995 to 1996 were
      compared with 51 patients diagnosed in 1997 to 1998. To analyze factors
      associated with survival we used a Cox model including antiretroviral therapy as
      a time-dependent covariate. RESULTS: Patients diagnosed in 1997 to 1998 were more
      likely to have TB as the first AIDS-defining illness (78% versus 58%, p <.05), to
      have HIV diagnosed <2 months before TB (33% vs. 7%, p <.005) and to have typical
      chest radiograph pattern (45% vs. 25%, p <.05), and had a higher CD4(+) count
      (median 105 vs. 43, p <.005). Survival at 1 year was 80% for patients diagnosed
      in 1997 to 1998 vs. 65% for those diagnosed in 1995 to 1996 (p by log-rank =.02).
      After adjusting at multivariate analysis, time period of diagnosis was not
      confirmed as associated with survival (hazard ratio, 1.05; 95% confidence
      interval, 0.39--2.81). Age, CD4+ cell count <25/mm(3), and AIDS-defining
      illnesses before TB diagnosis were all associated with an higher risk of death,
      whereas a decreased risk of death was observed in patients starting a triple
      combination antiretroviral therapy after TB diagnosis (hazard ratio, 0.14; 95%
      confidence interval, 0.03--0.57). CONCLUSIONS: Cases of HIV-associated TB
      occurring in patients with advanced immunosuppression and presenting with
      atypical radiologic appearance tend to be relatively less common in the HAART
      era. HAART is a major factor in prolonging survival in these patients.

PMID- 11317074
TI  - Open-label phase II trial of amprenavir, abacavir, and fixed-dose
      zidovudine/lamivudine in newly and chronically HIV-1--infected patients.
AB  - A Phase II clinical trial was designed to evaluate the efficacy and tolerability
      of twice-daily abacavir, amprenavir, and zidovudine (ZDV)/lamivudine (3TC) in HIV
      1-infected study subjects naive to protease inhibitors and 3TC. Plasma and
      cerebrospinal fluid (CSF) HIV-1 RNA levels and T-cell subsets were measured. In
      all, 27 newly diagnosed and 12 chronically HIV-1-infected study subjects are
      included in the analysis. Week 48 plasma HIV-1 RNA levels were <500 copies/ml in
      100% of study subjects, and <50 copies/ml in 80% of chronically infected and 100%
      of newly infected study subjects. The mean change in CD4 was (+)150 cells/microl
      (newly infected, p <.001), and (+)155 cells/microl (chronically infected, p
      <.001). At Week 48, evidence of cellular activation persisted in both cohorts. A
      twice-daily regimen of amprenavir, abacavir, and ZDV/3TC affords potent viral
      suppression and significant increases in total CD4(+) cells in HIV-1--infected
      study subjects. Patient intolerance may limit the efficacy of this combination.

PMID- 11317075
TI  - Effect of coexisting HIV-1 infection on the diagnosis and evaluation of hepatitis
      C virus.
AB  - OBJECTIVES: To evaluate the diagnostic accuracy of the test for antibodies to
      hepatitis C virus by enzyme-linked immunosorbent assay (anti-HCV ELISA-2) in
      patients with and without HIV-1 infection. DESIGN: Cohort study. METHODS: In all,
      369 patients were tested and grouped by available serologic tests. HCV RNA was
      quantified in these 369 patients using an Amplicor HCV (and/or HIV-1) Monitor,
      v1.0 test. Among 110 patients who were anti-HCV negative by ELISA-2, 39 were
      HIV/HBV coinfected and 71 had HIV alone. One hundred twelve patients were HIV/HCV
      coinfected and 147 patients had HCV infection alone. RESULTS: Six of 110 (5.5%)
      ELISA-2 anti-HCV-negative, HIV-infected patients had circulating serum HCV RNA.
      Their median CD4 count was 36 cells/mm(3), which was significantly lower than
      that observed in the HIV/HBV group (median CD4 = 109, p <.001) or the HIV/HCV
      cohort (CD4 = 235; p <.0001). The positive predictive value of the ELISA-2 test
      for diagnosing ongoing HCV infection in HIV-infected patients was 91%, which is
      significantly better than that determined for the HCV group, 76% (p =.002)
      presumably because HCV is less likely to resolve in the HIV patients. Mean
      alanine aminotransferase (ALT) levels were similar in the HIV/HCV (133 IU/L) and
      HCV (130 IU/L) cohorts. Median HCV RNA levels were higher in the HIV/HCV group
      (6.53 log(10) copies/ml) compared with the patients with HCV infection (5.62
      log(10) copies/ml; p <.00001). There was no significant correlation between HCV
      RNA levels and ALT values, CD4 counts, or HIV RNA concentrations. CONCLUSIONS:
      The predictive value of the anti-HCV ELISA-2 test is better in HIV-coinfected
      patients than in patients infected only with HCV. False negative results, usually
      associated with acute infection or with low CD4 counts, are uncommon. These
      patients may be diagnosed with the ELISA-3 assay or by reverse transcriptase
      polymerase chain reaction (RT-PCR). Compared with patients with only HCV
      infection, HIV/HCV patients display similar ALT profiles, but a higher proportion
      of detectable serum HCV RNA.

PMID- 11317076
TI  - HIV viral load in Thai men and women with subtype E infections.
AB  - The assessment of potential "breakthrough infections" in HIV vaccine trials
      requires knowledge of viral load in unvaccinated persons. Therefore, HIV-1 RNA
      was quantitated in plasma from Thai adults with subtype E infections. RNA was
      detectable (> or =500 copies/ml) in 93% of 255 specimens, with a mean (standard
      deviation) value of 4.09 (0.88) log copies/ml. The concentration of RNA was
      directly related to the presence of AIDS-defining illnesses, inversely related to
      CD4 count, and independent of gender after adjustment for CD4 count.

PMID- 11317077
TI  - HIV seroconversion during pregnancy and risk for mother-to-infant transmission.
AB  - Pregnant women infected with HIV-1 were enrolled in a prospective mother-to
      infant transmission study from 1992 through 1994 in Bangkok. In participating
      hospitals, voluntary HIV testing was routinely offered at the beginning of
      antenatal care and again in the middle of the third trimester of pregnancy. Women
      who seroconverted to HIV during pregnancy were compared with women who had tested
      positive on their first antenatal test. Maternal HIV RNA levels were determined
      during pregnancy, at delivery, and postpartum using RNA polymerase chain reaction
      (PCR), and infection status in infants was determined by DNA PCR. No infants were
      breast-fed, but prophylactic antiretroviral therapy was not yet used in Thailand
      to prevent transmission from mother to infant. Among enrolled women, 16 who
      seroconverted during pregnancy and 279 who were HIV-1-seropositive at their first
      antenatal test gave birth. Median plasma RNA levels at delivery were similar for
      the two groups (17,505 and 20,845 copies/ml, respectively; p =.8). Two (13.3%) of
      15 infants born to women who seroconverted and 66 (24.8%) of 266 infants born to
      previously HIV-seropositive women were infected with HIV (p =.5). There was no
      increased risk for mother-to-infant HIV transmission and no significant
      difference in viral load at delivery between HIV-infected women who seroconverted
      to HIV during pregnancy and those who were HIV-seropositive when first tested.

PMID- 11317078
TI  - Low carotenoid concentration and the risk of HIV seroconversion in Pune, India.
AB  - Low vitamin A and carotenoid levels could increase the risk of sexual HIV
      acquisition by altering the integrity of the genital epithelium or by immunologic
      dysfunction. We addressed this issue by measuring serum vitamin A and carotenoid
      levels in patients who were at risk of subsequent HIV infection. In a nested case
      control study in individuals attending two sexually transmitted disease (STD)
      clinics in Pune, India, serum micronutrient levels were measured in 44 cases with
      documented HIV seroconversion (11 women and 33 men) and in STD patients matched
      for gender and length of follow-up with no subsequent HIV seroconversion
      (controls). STD patients in Pune had low vitamin A and carotenoid levels, and low
      serum beta-carotene levels were independently associated with an increased risk
      of subsequent HIV seroconversion. STD patients with beta-carotene levels less
      than 0.075 micromol/L were 21 times more likely to acquire HIV infection than
      those with higher levels (adjusted odds ratio = 21.1; p =.01). No such
      association was observed in case of other non-provitamin A carotenoids. This
      study reports the first evidence of an association between low serum provitamin A
      carotenoid levels and an increased risk for heterosexual HIV acquisition in STD
      patients in Pune, India.

PMID- 11317079
TI  - Selenium deficiency is associated with shedding of HIV-1--infected cells in the
      female genital tract.
AB  - OBJECTIVE: To assess the relation between selenium deficiency and vaginal or
      cervical shedding of HIV-1-infected cells. DESIGN: Cross-sectional study of 318
      HIV-1 seropositive women in Mombasa, Kenya. METHODS: Vaginal and cervical swab
      specimens were tested for the presence of HIV-1 DNA by polymerase chain reaction.
      Multivariate logistic regression models, adjusting for CD4 count and vitamin A
      deficiency, were used. RESULTS: Selenium deficiency (defined as levels <85
      microg/L) was observed in 11% of the study population. In unstratified
      multivariate analyses, there was no significant association between selenium
      deficiency and vaginal or cervical shedding. In stratified analyses, however,
      significant associations became apparent after excluding women with predictors of
      shedding with strong local effects on the genital tract mucosa. Among women who
      did not use oral contraceptives and who did not have vaginal candidiasis,
      selenium deficiency was significantly associated with vaginal shedding (adjusted
      odds ratio [AOR] 2.9, 95% confidence interval [CI] 1.0--8.8, p =.05). Effect
      modification was also observed in the relation between selenium deficiency and
      cervical shedding, with a significant association seen among those women who were
      not using oral contraceptive pills or depot medroxyprogesterone acetate and who
      did not have Neisseria gonorrhoeae infection (AOR 2.8, 95% CI 1.1--7.0, p =.02).
      CONCLUSIONS: We found selenium deficiency to be associated with a nearly
      threefold higher likelihood of genital mucosal shedding of HIV-1--infected cells,
      suggesting that deficiency may increase the infectiousness of women with HIV-1.
      Nutritional interventions to prevent HIV-1 transmission warrant investigation.

PMID- 11317080
TI  - Changes in HIV-1 incidence in heroin users in Guangxi Province, China.
AB  - Guangxi Province, China recently experienced an outbreak of HIV-1 infection among
      heroin users. We studied HIV-1 incidence rates and associated risk factors for
      HIV-1 infection among heroin users residing in Pingxiang City. A total of 318
      heroin users were followed from February 1998 through January 1999 (median follow
      up: 8.1 months). Of these, 130 were prospectively followed from January through
      September 1999 (median follow-up: 8.3 months). HIV-1 and hepatitis C virus (HCV)
      incidence rates for each period were calculated. A generalized estimating
      equation approach was implemented to identify independent risk factors associated
      with HIV-1 infection across both periods. Among 318 study participants, 97.2%
      were men. The median age was 22 years. Approximately 60% reported sharing
      needles. HIV-1 prevalence at baseline was 15.4%. During the first follow-up
      period, HIV-1 incidence was 2.38 per 100 person years (py), and HCV incidence was
      26.8 per 100 py. During the second follow-up period, HIV-1 incidence was 6.86 per
      100 py, and HCV incidence was 28.9 per 100 py. After controlling for age and
      other factors, HCV seropositivity, history of sexually transmitted diseases, and
      sharing needles were independently associated with HIV-1 infection. These data
      suggest that HIV-1 incidence was rising over time in Pingxiang City, Guangxi
      Province. The high incidence of HCV heightens the importance of enhanced
      prevention programs to reduce injection and needle sharing among heroin users.

PMID- 11317081
TI  - Risk of T-cell lymphomas in persons with AIDS.
AB  - Lymphomas in persons with AIDS are mostly B-cell types, but T-cell lymphomas have
      also been reported. We examined T-cell lymphoma risk in the 2-year period after
      AIDS onset by linking 302,834 adults with AIDS to cancer registry data. Of 6,788
      cases of non-Hodgkin's lymphoma (NHL) with specified histologies, 96 (1.4%) were
      T-cell lymphomas. Assessment was based on clinical diagnosis and histology
      because T-cell marker data were inadequate, but when present, marker data
      supported the T-cell diagnosis. The relative risk of T-cell lymphoma, estimated
      by standardized incidence ratio, was 15.0 (95% confidence interval: 10.0--21.7).
      Risks were increased for all subtypes, including mycosis fungoides, peripheral
      lymphomas, cutaneous lymphomas, and adult T-cell leukemia/lymphoma (ATLL). HIV
      related immunodeficiency could be important, but differences between the
      population developing AIDS and the general population (e. g., immigration from
      the Caribbean region for ATLL) might independently increase T-cell lymphoma risk.

PMID- 11317082
TI  - Incidence of invasive cervical cancer in a cohort of HIV-seropositive women
      before and after the introduction of highly active antiretroviral therapy.
AB  - To assess whether the incidence of invasive cervical cancer (ICC) has changed as
      a result of highly active antiretroviral therapy (HAART), we conducted a
      prospective cohort study on the incidence of ICC before and after the
      introduction of HAART among Italian women with a known duration of HIV infection.
      We estimated the incidence per 1000 person years of ICC as a first AIDS-defining
      disease for the periods 1981 through 1991, 1992 through 1995, and 1996 through
      1998. We also estimated the incidence of other first AIDS-defining diseases.
      Kaplan-Meier and Cox models were applied to compare the periods 1981 through 1995
      and 1996 through 1998 in terms of cumulative incidence and relative hazards
      (RHs). The analysis included 483 women (median follow-up: 7 years). In the period
      1981 through 1995, a trend of increase was observed in the incidence of ICC and
      other AIDS-defining diseases; this trend has continued only for ICC, whereas the
      incidence of other AIDS-defining diseases has decreased since 1996. Compared with
      1981 through 1995, the RH of ICC for 1996 through 1998 was 7.41 (95% confidence
      interval [CI]: 1.21--45.44); when adjusting for age at HIV seroconversion, the RH
      decreased to 4.75 (95% CI: 0.80--28.24). It remains to be determined whether the
      continued increase in ICC incidence after the introduction of HAART is
      attributable to a decreasing competitive mortality from other AIDS-defining
      diseases among HIV-infected women.

PMID- 11317083
TI  - National surveillance of HIV-1 subtypes for England and Wales: design, methods,
      and initial findings.
AB  - The HIV-1 infections detected in an ongoing national unlinked anonymous HIV
      surveillance program were subtyped and analyzed according to demographic and risk
      characteristics. Of the 893 anti--HIV-1--positive specimens allocated to an
      exposure group, 70% could be subtyped. Almost 25% of infections subtyped were non
      B, mostly subtypes A, C, and D. Non-B infections were rare in homosexual and
      bisexual men and in drug injectors. Forty percent of infections in heterosexual
      men attending genitourinary medicine clinics were non-B subtypes; of these, 25%
      were subtype A infections and 59% were subtype C infections. For female clinic
      attendees, 61% were non-B subtype infections, of which 48% were subtype A
      infections and 42% were subtype C infections. Of the clinic attendees born in the
      United Kingdom and Europe, 14% of the men and 35% of the women were infected with
      non-B subtypes. In contrast, 78% of infections in antenatal patients were non-B
      subtypes, of which 61% were subtype A and 29% were subtype C. Extrapolation to
      the estimated 29,700 prevalent adult infections in the United Kingdom indicates
      that approximately 8,100 (27%) such infections are non-B subtypes and that these
      are found almost entirely in heterosexuals. The findings suggest spread of
      infection of non-B subtypes to heterosexuals born in the United Kingdom from
      individuals infected in regions of high prevalence.

PMID- 11317085
TI  - Variations in institutional review board decisions for HIV quality of care
      studies: a potential source of study bias.

PMID- 11317084
TI  - Persistent dyslipidemia in HIV-infected individuals switched from a protease
      inhibitor-containing to an efavirenz-containing regimen.

PMID- 11317086
TI  - Performance of a quadruple combination including nelfinavir plus efavirenz in
      naive subjects with high baseline viral load and in patients failing protease
      inhibitor-containing regimens.

PMID- 11317087
TI  - Prevalence of HIV antibodies in replacement blood donors in Delhi, India.

PMID- 11317088
TI  - Different pattern of AIDS-defining diseases in persons responding to highly
      active antiretroviral therapy.

PMID- 11317089
TI  - Issues of adherence, penetration, and measurement in physical activity
      effectiveness studies.

PMID- 11317090
TI  - Economic evaluation of aquatic exercise for persons with osteoarthritis.
AB  - OBJECTIVES: To estimate cost and outcomes of the Arthritis Foundation aquatic
      exercise classes from the societal perspective. DESIGN: Randomized trial of 20
      week aquatic classes. Cost per quality-adjusted life year (QALY) gained was
      estimated using trial data. Sample size was based on 80% power to reject the null
      hypothesis that the cost/QALY gained would not exceed $50,000. SUBJECTS AND
      METHODS: Recruited 249 adults from Washington State aged 55 to 75 with a doctor
      confirmed diagnosis of osteoarthritis to participate in aquatic classes. The
      Quality of Well-Being Scale (QWB) and Current Health Desirability Rating (CHDR)
      were used for economic evaluation, supplemented by the arthritis-specific Health
      Assessment Questionnaire (HAQ), Center for Epidemiologic Studies-Depression Scale
      (CES-D), and Perceived Quality of Life Scale (PQOL) collected at baseline and
      postclass. Outcome results applied to life expectancy tables were used to
      estimate QALYs. Use of health care facilities was assessed from
      diaries/questionnaires and Medicare reimbursement rates used to estimate costs.
      Nonparametric bootstrap sampling of costs/QALY ratios established the 95% CI
      around the estimates. RESULTS: Aquatic exercisers reported equal (QWB) or better
      (CHDR, HAQ, PQOL) health-related quality of life compared with controls. Outcomes
      improved with regular class attendance. Costs/QALY gained discounted at 3% were
      $205,186 using the QWB and $32,643 using the CHRD. CONCLUSION: Aquatic exercise
      exceeded $50,000 per QALY gained using the community-weighted outcome but fell
      below this arbitrary budget constraint when using the participant-weighted
      measure. Confidence intervals around these ratios suggested wide variability of
      cost effectiveness of aquatic exercise.

PMID- 11317091
TI  - Educational program for physicians to reduce use of non-steroidal anti
      inflammatory drugs among community-dwelling elderly persons: a randomized
      controlled trial.
AB  - CONTEXT: Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most
      frequently prescribed drugs for patients 65 years of age or older, primarily for
      musculoskeletal symptoms of osteoarthritis. Because NSAIDs frequently cause
      serious gastrointestinal (GI) and other complications among elderly patients,
      expert guidelines for osteoarthritis recommend acetaminophen-based regimens,
      which are safer and often as effective as NSAIDs. OBJECTIVE: Evaluate a physician
      education program that communicated guidelines for management of osteoarthritis
      in elderly patients that emphasized avoidance of NSAIDs when possible. The
      program reviewed NSAID risks and benefits and recommended: re-evaluating
      continuous NSAID users, considering substitution of up to 4 g/d of acetaminophen
      for the NSAID, and trying topical agents and nonpharmacologic measures. DESIGN
      AND SETTING: Randomized controlled trial among community-dwelling Tennessee
      Medicaid enrollees. SUBJECTS: Study physicians had 5 or more patients who: were
      community-dwelling Medicaid enrollees 65 years of age or older; had used NSAIDs
      regularly for at least 180 days; had had no medical care encounters during this
      period suggesting an indication other than osteoarthritis; and had 1 year of
      baseline and follow-up data. The study thus included 209 physicians (103
      intervention/106 control) with 1,566 qualifying regular NSAID users (768/798).
      INTERVENTIONS: Face-to-face visit to study physicians by another physician, and
      reminder placements in the charts of patients eligible to have NSAID use
      reevaluated. OUTCOMES: Change between baseline and follow-up years in: days of
      prescribed NSAIDs, acetaminophen, other drugs for musculoskeletal disorders, and
      GI drugs; outpatient visits and inpatient days of stay; SF36 measures of general
      health, physical function, and bodily pain (from 40% random patient sample); and
      over-the-counter NSAIDs (from the sample). RESULTS: Intervention-attributable
      reduction of 7% (95% CI, 3% to 11%) in days of prescribed NSAIDs use with
      concomitant increase in acetaminophen use. No significant changes in other study
      endpoints. The intervention effect was greater among 75 physicians with a
      completed study visit, whose 564 patients had a 10% (95% CI, 6% to 14%)
      attributable reduction in NSAID use. CONCLUSIONS: The educational program
      modestly reduced NSAID exposure in community-dwelling elderly patients without
      undesirable substitution of other medications or detectable worsening of
      musculoskeletal symptoms.

PMID- 11317092
TI  - Educational program for nursing home physicians and staff to reduce use of non
      steroidal anti-inflammatory drugs among nursing home residents: a randomized
      controlled trial.
AB  - CONTENT: The risk for serious gastrointestinal complications due to nonsteroidal
      anti-inflammatory drugs (NSAIDs) is high in the elderly. Acetaminophen-based
      regimens are safer and may be as effective as NSAIDs for the treatment of
      osteoarthritis in many patients. OBJECTIVE: To determine the effects of an
      educational program on NSAID use and clinical outcomes in nursing homes. DESIGN
      AND SETTING: Randomized controlled study. Ten pairs of Tennessee nursing homes
      with > or = 8% of residents receiving NSAIDs were randomized to intervention or
      control. SUBJECTS: Nursing home residents (intervention n = 76 and control n =
      71) aged 65 years and older taking NSAIDs regularly. INTERVENTIONS: An
      educational program for physicians and nursing home staff that included the risks
      and benefits of NSAIDs in the elderly and an algorithm that substituted
      acetaminophen, topical agents, and nonpharmacologic measures for the treatment of
      noninflammatory musculoskeletal pain. Intervention and control subjects were
      assessed at baseline and 3 months later. MAIN OUTCOME MEASURES: Differences in
      NSAID and acetaminophen use, and pain, function, and disability scores in
      intervention and control nursing home subjects. RESULTS: The intervention was
      effective resulting in markedly decreased NSAID use and increased acetaminophen
      use. Mean number of days of NSAID use in the 7 day periods before the baseline
      and 3 month assessments decreased from 7.0 to 1.9 days in intervention home
      subjects compared with a decrease from 7.0 to 6.2 days in control homes (P =
      0.0001). Acetaminophen use in the 7 days immediately before the 3 month
      assessment increased by 3.1 days in intervention home subjects compared with 0.31
      days in control homes (P = 0.0001). A similar proportion of subjects in control
      (32.5%) and intervention (35.4%) groups had worsening of their arthritis pain
      score (P = 0.81). CONCLUSIONS: An educational intervention effectively reduced
      NSAID use in nursing homes without worsening of arthritis pain.

PMID- 11317093
TI  - Impact of underuse, overuse, and discretionary use on geographic variation in the
      use of coronary angiography after acute myocardial infarction.
AB  - BACKGROUND: Geographic variation in the use of medical procedures has been well
      documented. However, it is not known whether this variation is due to differences
      in use when procedures are indicated, discretionary, or contraindicated.
      OBJECTIVES: To examine whether use of coronary angiography after acute myocardial
      infarction (AMI) according to appropriateness criteria varied across geographic
      regions and whether underuse, overuse, or discretionary use accounted for
      variation in overall use. DESIGN: Retrospective cohort study using data from the
      Cooperative Cardiovascular Project. SETTING: Ninety-five hospital referral
      regions. PATIENTS: There were 44,294 Medicare patients hospitalized with AMI
      during 1994 or 1995, classified according to appropriateness for angiography.
      MAIN OUTCOME MEASURE: Variation in use of angiography, as measured by the
      difference between high and low rates of use across regions. RESULTS: Across
      regions, variation in the use of angiography was similar for indications judged
      necessary; appropriate, but not necessary; or uncertain. Variation was lowest for
      indications judged unsuitable (difference between high rate and low rate across
      regions = 16.3%; 95% CI = 12.6%; 20.6%). The primary cause of variation in the
      overall rate of angiography was due to use for indications judged appropriate,
      but not necessary or uncertain. When variation associated with these indications
      was accounted for, the difference between the resulting high and low overall
      rates was 10.8% (9.4%, 12.4%). In contrast, variation in the overall rate
      remained high when underuse in necessary situations or overuse in unsuitable
      situations was accounted for. CONCLUSIONS: Across regions, practice was more
      similar for patients categorized unsuitable for angiography than for patients
      with other indications. Variation in overall use of angiography appeared to be
      driven by utilization for discretionary indications rather than by underuse or
      overuse. If equivalent rates across geographic areas are judged desirable, then
      greater effort must be directed toward defining care for patients with
      discretionary indications.

PMID- 11317094
TI  - Impact of double counting and transfer bias on estimated rates and outcomes of
      acute myocardial infarction.
AB  - CONTEXT: Ischemic heart disease is the leading cause of death in the United
      States. Recent studies report inconsistent findings on the changes in the
      incidence of hospitalizations for ischemic heart disease. These reports have
      relied primarily on hospital discharge data. Preliminary data suggest that a
      significant percentage of patients suffering acute myocardial infarction (MI) in
      rural communities are transferred to urban centers for care. Patients transferred
      to a second hospital may be counted twice for one episode of ischemic heart
      disease. OBJECTIVE: To describe the impact of double counting and transfer bias
      on the estimation of incidence rates and outcomes of ischemic heart disease,
      specifically acute MI, in the United States. DESIGN: Analysis of state hospital
      discharge data from Kansas, Colorado (State Inpatient Database [SID]), Nebraska,
      Arizona, New Jersey, Michigan, Pennsylvania, and Illinois (SID) for the years
      1995 to 1997. A matching algorithm was developed for hospital discharges to
      determine patients counted twice for one episode of ischemic heart disease.
      Validation of our matching algorithm. PATIENTS: Patients reported to have
      suffered ischemic heart disease (ICD9 codes 410-414, 786.5). MAIN OUTCOME
      MEASURES: Number of patients counted twice for one episode of acute MI. RESULTS:
      It is estimated that double count rates range from 10% to 15% for all states and
      increased over the 3 years. Moderate sized rural counties had the highest
      estimated double count rates at 15% to 20% with a few counties having estimated
      double count rates a high as 35% to 50%. Older patients and females were less
      likely to be double counted (P <0.05). CONCLUSIONS: Double counting patients has
      resulted in a significant overestimation in the incidence rate for
      hospitalization for acute MI. Correction of this double counting reveals a
      significantly lower incidence rate and a higher in-hospital mortality rate for
      acute MI. Transferred patients differ significantly from nontransferred patients,
      introducing significant bias into MI outcome studies. Double counting and
      transfer bias should be considered when conducting and interpreting research on
      ischemic heart disease, particularly in rural regions.

PMID- 11317095
TI  - To help or hinder: Which is more important in explaining a physician's
      willingness to recommend a health plan?
AB  - PURPOSE: To examine how specific health plan practices contribute to physicians'
      willingness to recommend a health plan to a patient, and whether the relative
      importance of plan practices is viewed differently when patients are seriously
      ill. METHODS: The Physician's Evaluation of Health Plans Project has surveyed
      1,757 generalist physicians in 16 health plans in 5 areas nationwide. Each
      physician reported on one plan. Three multi-item scales assessed physicians'
      perceptions of health plan activities that facilitated or impeded high-quality
      care in the plans and the clinical capabilities of plan physicians. Regression
      analyses were used to explore relations between facilitators, barriers, and
      clinical capabilities, and two global physician judgments (the physician's
      willingness to recommend a plan and their judgment that a plan provided lower
      quality for sicker patients). RESULTS: A physician's willingness to recommend a
      health plan is more highly related to what plans do to facilitate care than to
      the barriers created by plans in managing care. However, barriers to care were
      substantially more important when evaluating health plan quality for sicker
      patients. CONCLUSIONS: From the physician's perspective, the relative importance
      of plan strategies to manage care is different for typical patients and patients
      who are more seriously ill. Efforts to collect information on health plan quality
      should separately evaluate care for sicker patients, in addition to evaluating
      the overall performance of the health plan.

PMID- 11317096
TI  - Assessing health system provision of adolescent preventive services: the Young
      Adult Health Care Survey.
AB  - BACKGROUND: Adolescents often do not receive recommended preventive counseling
      and screening services. Few measures are available to assess health care system
      performance in this area. OBJECTIVE: Develop a reliable, valid, and feasible
      method for measuring adherence to consensus guidelines for adolescent preventive
      counseling and screening services. METHODS: The 45-item Young Adult Health Care
      Survey (YAHCS) was tested with a diverse group of commercially and publicly
      insured adolescents enrolled in managed care organizations (n = 4,060).
      Psychometric, bivariate, and multivariate analyses were conducted to assess the
      reliability, validity, and patterns of variation in the preventive care
      measurement scales derived from the YAHCS. RESULTS: YAHCS measurement scales
      demonstrated strong construct validity (mean factor loading = 0.64) and
      reliability (mean Cronbach's alpha = 0.77). Average preventive counseling and
      screening scores ranged from 18.2% for discussing risky behavior topics to 50.4%
      for discussing diet, weight, and exercise topics. Adolescent demographic, health
      care use, and payer factors explained a small amount of variation across
      adolescent scores on YACHS scales (mean R2 = 0.086). Females and older teens were
      more likely to report private time with providers and counseling and screening on
      topics related to sex. Overall, the odds of receiving preventive counseling and
      screening for adolescents who reported having private time with providers,
      engaging in risky behaviors, or both were higher than for adolescents who did not
      meet privately or report risky behaviors (private visit OR, 3.60; 95% CI, 2.91
      4.47; risky behaviors OR, 2.02; 95% CI, 1.62-2.52). CONCLUSIONS: The YAHCS
      provides a feasible, reliable, and valid method for assessing adherence to
      adolescent preventive services guidelines. It differentiates among varied aspects
      of preventive care provided to adolescents and is promising as a potential
      measure of health plan and provider quality. Improved performance on the YAHCS
      would indicate progress toward the achievement of Healthy People 2010 goals.

PMID- 11317097
TI  - Provider type and the receipt of general and diabetes-related preventive health
      services among patients with diabetes.
AB  - OBJECTIVE: Using a measure of provider type that includes "shared care" to
      determine the contribution of provider type on receipt of general and diabetes
      related preventive health services. METHODS: Automated clinical and
      administrative data were used to identify adult patients with type 1 and 2
      diabetes receiving care from a multispecialty, salaried group practice and
      enrolled in a large health maintenance organization between 3/97 and 2/98 (n =
      10,991). Logistic regression models were fit using generalized estimating
      equation approaches to evaluate the contribution of provider type on service
      receipt. MEASURES: Preventive service receipt included receipt of glycated
      hemoglobin and lipid testing, retinal examinations, pneumococcal vaccines,
      Papanicolaou (Pap) smears, and mammograms. Multivariable analyses adjusted for
      age, sex, race, marital status, household income, diabetes-related comorbidities
      and complications, prescription drug use, laboratory testing results, and
      frequency of medical care contact. RESULTS: Patients seeing an endocrinologist
      and primary care physician (PCP) were more likely than those seeing
      endocrinologists alone to receive glycated hemoglobin testing (OR, 1.42), lipid
      testing (OR, 1.72), mammograms (OR, 2.12), and Pap smears (OR, 2.36), and more
      likely than those seeing PCPs alone to receive glycated hemoglobin testing (OR,
      1.79), lipid testing (OR, 1.54), retinal examinations (OR, 1.33), and mammograms
      (OR, 1.43). Compared with patients seeing PCPs only, patient's seeing
      endocrinologists only were more likely to receive retinal examinations (OR, 1.37)
      and less likely to receive Pap smears (OR, 0.46). CONCLUSIONS: Care delivered by
      no one single provider type is associated with greater receipt of all recommended
      services. Instead, patients seeing both an endocrinologist and a PCP are most
      likely to receive recommended services.

PMID- 11317098
TI  - UPBEAT: the impact of a psychogeriatric intervention in VA medical centers.
      Unified Psychogeriatric Biopsychosocial Evaluation and Treatment.
AB  - BACKGROUND: The Unified Psychogeriatric Biopsychosocial Evaluation and Treatment
      (UPBEAT) program provides individualized interdisciplinary mental health
      treatment and care coordination to elderly veterans whose comorbid depression,
      anxiety, or alcohol abuse may result in overuse of inpatient services and
      underuse of outpatient services. OBJECTIVES: To determine whether proactive
      screening of hospitalized patients can identify unrecognized comorbid psychiatric
      conditions and whether comprehensive assessment and psychogeriatric intervention
      can improve care while reducing inpatient use. DESIGN: Randomized trial.
      SUBJECTS: Veterans aged 60 and older hospitalized for nonpsychiatric medical or
      surgical treatment in 9 VA sites (UPBEAT, 814; usual care, 873). MEASURES: The
      Mental Health Inventory (MHI) anxiety and depression subscales, the Alcohol Use
      Disorder Identification Test (AUDIT) scores, RAND 36-Item Health Survey Short
      Form (SF-36), inpatient days and costs, ambulatory care clinic stops and costs,
      and mortality and readmission rates. RESULTS: Mental health and general health
      status scores improved equally from baseline to 12-month follow-up in both
      groups. UPBEAT increased outpatient costs by $1,171 (P <0.001) per patient, but
      lowered inpatient costs by $3,027 (P = 0.017), for an overall savings of $1,856
      (P = 0.156). Inpatient savings were attributable to fewer bed days of care (3.30
      days; P = 0.016) rather than fewer admissions. Patients with 1 or more pre
      enrollment and postenrollment hospitalizations had the greatest overall savings
      ($6,015; P = 0.069). CONCLUSIONS: UPBEAT appears to accelerate the transition
      from inpatient to outpatient care for acute nonpsychiatric admissions. Care
      coordination and increased access to ambulatory psychiatric services produces
      similar improvement in mental health and general health status as usual care.

PMID- 11317099
TI  - Effect of specialty and nationality on panel judgments of the appropriateness of
      coronary revascularization: a pilot study.
AB  - BACKGROUND: Appropriateness criteria are frequently used to assess quality of
      care. However, assessing care in one country with criteria developed in another
      may be misleading. One approach to measuring care across countries would be to
      develop common standards using physicians from different countries and
      specialties. OBJECTIVE: To identify the degree to which appropriateness ratings
      for coronary revascularization developed by a multinational panel differ by
      panelist specialty and nationality. METHODS: A 13-member panel of cardiothoracic
      surgeons and cardiologists from the Netherlands, Spain, Sweden, Switzerland, and
      the United Kingdom was convened to rate the appropriateness of 842 indications
      for percutaneous transluminal coronary angioplasty (PTCA) and coronary artery
      bypass graft surgery (CABG) on a 1 (extremely inappropriate) to 9 (extremely
      appropriate) scale. MEASURES: Mean appropriateness ratings by panelist specialty
      and nationality. RESULTS: Surgeons' mean ratings for PTCA indications ranged from
      0.64 points lower than the corresponding ratings of the cardiologists for acute
      myocardial infarction indications to 1.22 points lower for chronic stable angina
      indications. Conversely, their ratings for bypass surgery indications ranged from
      0.59 points higher for chronic stable angina indications to 0.69 points higher
      for unstable angina indications. Although Spanish panelists' ratings were
      significantly higher than the mean for 3 of the 4 clinical conditions treated by
      PTCA, their ratings were similar for bypass surgery indications. No specific
      patterns were observed in the ratings of the panelists from the other countries.
      CONCLUSIONS: These findings support the use of physicians from multiple
      specialties on appropriateness panels because they represent more divergent views
      than physicians from a single specialty. Finding no systematic difference in
      beliefs regarding the appropriateness of PTCA and CABG among physicians from
      different countries will require confirmation before multinational panels
      supplant single country panels in future studies.

PMID- 11317102
TI  - Evaluation of carriers of bone morphogenetic protein for spinal fusion.

PMID- 11317103
TI  - 2000 International society for the study of the lumbar spine presidential
      address: backs to work: some reflections.

PMID- 11317104
TI  - Assessment of back-related quality of life: the continuing challenge.
AB  - It is always gratifying to be acknowledged by a colleague and asked to give a
      talk in a faraway land about a topic of one's particular interest. To be invited,
      however, to give the Harry Farfan Presidential Lecture at the 27th Meeting of the
      International Society for the Study of the Lumbar Spine is, for me, a special
      honor and privilege. Too many years ago, when I was a very junior faculty member
      at the School of Physical and Occupational Therapy at McGill University in
      Montreal, Canada, we offered our students a course in Orthopedic Conditions. This
      course was primarily taught by orthopedic surgeons, rheumatologists, and other
      members of the medical profession with special interest in disorders of the
      musculoskeletal system. Teaching in this course was considered to be a
      professional obligation at McGill, and, while most individuals accepted the
      invitation, they did so with varying degrees of enthusiasm. Each year, Dr. Harry
      Farfan graciously agreed and provided several lectures for our students. He told
      them about the surgical management of problems of the lumbar spine and the
      necessity of treating the "whole" patient, as well as about his theory as to the
      cause of low back pain. At that point in time, we were not talking about quality
      of life as an outcome of care for our patients, but I cannot help but believe
      that he would keenly approve of the subject of this presentation.

PMID- 11317106
TI  - Selective inhibition of tumor necrosis factor-alpha prevents nucleus pulposus
      induced thrombus formation, intraneural edema, and reduction of nerve conduction
      velocity: possible implications for future pharmacologic treatment strategies of
      sciatica.
AB  - STUDY DESIGN: The possibility to prevent nucleus pulposus-induced functional and
      structural nerve root injury by selective tumor necrosis factor-alpha inhibition
      was assessed in an experimental model in the pig spine. OBJECTIVE: The objective
      of the study was to evaluate the role of tumor necrosis factor-alpha in the
      mediation of nucleus pulposus-induced nerve injury by using selective inhibition.
      SUMMARY OF BACKGROUND DATA: The cytokine tumor necrosis factor-alpha has been
      suggested to play a key role in the nerve root injury induced by local
      application of nucleus pulposus. However, previous studies have not been able to
      distinguish the effects between tumor necrosis factor-alpha and other disc
      related cytokines because of the use of nonspecific cytokine inhibition. METHODS:
      Autologous nucleus pulposus was harvested from a lumbar disc and applied to the
      porcine sacrococcygeal cauda equina. The pigs were simultaneously treated with
      two selective tumor necrosis factor-alpha inhibitors (etanercept n = 8 and
      infliximab n = 5), a heparin analogue (enoxaparin n = 5) or saline for control (n
      = 5). After 7 days the nerve conduction velocity over the application zone was
      determined and samples of the exposed nerve roots were collected for light
      microscopic evaluation. RESULTS: The two tumor necrosis factor-alpha inhibitors
      prevented the reduction of nerve conduction velocity and also seemed to limit the
      nerve fiber injury, the intracapillary thrombus formation, and the intraneural
      edema formation. However, treatment with enoxaparin did not seem to be different
      from control regarding reduction of nerve conduction velocity or histologic
      changes. CONCLUSIONS: The data clearly indicate that tumor necrosis factor-alpha
      is involved in the basic pathophysiologic events leading to nerve root structural
      and functional changes after local application of nucleus pulposus. The study
      therefore provides a basic scientific platform with potential clinical
      implications regarding the use of anti-tumor necrosis factor-alpha medication as
      treatment in patients with disc herniation and sciatica.

PMID- 11317107
TI  - Prevention of compartment syndrome in dorsal root ganglia caused by exposure to
      nucleus pulposus.
AB  - STUDY DESIGN: An experimental study to clarify the effects of pentoxifylline, as
      an anti-tumor necrosis factor-alpha therapy on endoneurial fluid pressure in the
      dorsal root ganglion using an animal model of herniated nucleus pulposus.
      OBJECTIVES: To investigate the effects of anti-tumor necrosis factor-alpha
      therapy to nucleus pulposus-induced nerve root/dorsal root ganglion changes.
      SUMMARY OF BACKGROUND DATA: It has been reported experimentally that application
      of nucleus pulposus into epidural space induces morphologic and functional
      changes in the nerve roots and induces compartment syndrome in the dorsal root
      ganglia. Tumor necrosis factor-alpha has been considered a key pathogenic factor
      in the initiation and maintenance of neuropathic pain states. METHODS: A total of
      11 adult, female Sprague-Dawley rats had their left L5 nerve roots and associated
      dorsal root ganglions exposed. Autologous nucleus pulposus was applied to the L5
      nerve root just proximal to the dorsal root ganglion. A piece of Spongel
      (Yamanouchi Pharmaceutical Co., Tokyo) containing 20 microL of 1000 microg/mL
      pentoxifylline was applied with the nucleus pulposus (NP+PTX group). In control
      animals nucleus pulposus was applied with a piece of Spongel containing 20 microL
      of physiologic saline solution in a similar fashion (NP+PS group). Endoneurial
      fluid pressure was recorded with a servo-null micropipette system using glass
      micropipettes with tip diameters of 4 microm. Endoneurial fluid pressure in the
      dorsal root ganglion was measured before and 3 hours after application of test
      substances. After measurement of endoneurial fluid pressure, the nerve root and
      dorsal root ganglion were processed for histology and evaluated by light
      microscope. RESULTS: Values of endoneurial fluid pressure before application of
      test substances were as follows: 2.4 +/- 1.2 cm H2O in the NP+PS (control) group
      and 1.8 +/- 0.4 cm H2O in the NP+PTX group. There was no statistically
      significant difference between these two pretreatment measurements. However,
      values of endoneurial fluid pressure after application were as follows: 8.6 +/-
      1.8 cm H2O in the NP+PS group and 2.9 +/- 0.8 cm H2O in the NP+PTX group. Values
      of endoneurial fluid pressure in the NP+PTX group were significantly lower
      compared with the NP+PS group. Histologic examination consistently showed only a
      slight degree of edema evident in the NP+PTX group compared with the NP+PS group.
      CONCLUSION: Pentoxifylline, an anti-tumor necrosis factor-alpha drug, prevented
      the dorsal root ganglion compartment syndrome caused by topical application of
      nucleus pulposus. Anti-inflammatory cytokine therapy may become an effective
      treatment of sciatica due to disc herniation.

PMID- 11317109
TI  - Morphologic changes in the lumbar intervertebral foramen due to flexion
      extension, lateral bending, and axial rotation: an in vitro anatomic and
      biomechanical study.
AB  - STUDY DESIGN: A biomechanical and anatomic study with human cadaveric lumbar
      spine. OBJECTIVES: The purpose of this study is to examine the morphologic
      changes in the intervertebral foramen during flexion, extension, lateral bending,
      and axial rotation of the lumbar spine and to correlate these changes with the
      flexibility of the spinal motion segments. SUMMARY OF BACKGROUND DATA: Previous
      studies showed morphologic changes in the intervertebral foramen during flexion
      and extension; however, those changes during lateral bending and axial rotation
      were not well known. METHODS: There were 81 motion segments obtained from 39
      human cadaveric lumbar spines (mean age 69 years). The motion segments were
      imaged with CT scanner with 1-mm thick consecutive sections. For biomechanical
      testing each motion segment was applied with incremental pure moments of flexion,
      extension, lateral bending, and axial rotation. Rotational movements of the
      motion segment were measured using VICON cameras. After application of the last
      load, the specimens were frozen under load, and then CT was performed with the
      same technique described above. Six parameters of the intervertebral foramen were
      measured, including foraminal width (maximum and minimum), foraminal height, disc
      bulging, thickness of ligamentum flavum, and cross-sectional area of the foramen.
      RESULTS: Flexion increased the foraminal width (maximum and minimum), height, and
      area significantly while significantly decreasing the disc bulging and thickness
      of ligamentum flavum (P < 0.05). However, extension decreased the foraminal width
      (maximum and minimum), height, and area significantly. Lateral bending
      significantly decreased the foraminal width (maximum and minimum), height, and
      area at the bending side, whereas lateral bending significantly increased the
      foraminal width (minimum), height, and area at the opposite side of bending.
      Likewise, axial rotation decreased the foraminal width (minimum) and area at the
      rotation side significantly while significantly increasing the foraminal height
      and foraminal area at the opposite side. The percent change in the foraminal area
      was found significantly correlated with the amount of segmental spinal motion
      except for the extension motion. CONCLUSIONS: This study showed that the
      intervertebral foramen of the lumbar spine changed significantly not only on
      flexion-extension but also on lateral bending and axial rotation. The percent
      change in cross-sectional foraminal area was correlated with the amount of
      segmental motion except for extension motions. Further studies are needed to
      assess the morphologic changes in the intervertebral foramen in vivo and to
      correlate clinically.

PMID- 11317110
TI  - Effect of frozen storage on the creep behavior of human intervertebral discs.
AB  - STUDY DESIGN: A biomechanical study of the compressive creep behavior of the
      human intervertebral disc before and after frozen storage. OBJECTIVES: To
      determine whether frozen storage alters the time-dependent response of the intact
      human intervertebral disc. SUMMARY OF BACKGROUND DATA: The biomechanical
      properties of the intervertebral disc are generally determined using specimens
      that have been previously frozen. Although it is well established that freezing
      does not alter the elastic response of the disc, recent data demonstrate that
      freezing permanently alters the time-dependent mechanical behavior of porcine
      discs. METHODS: Twenty lumbar motion segments from 10 human spines were harvested
      between 12 and 36 hours postmortem. The specimens were randomly assigned to one
      of two groups: Group 1 was tested promptly, stored frozen for 3 weeks, then
      thawed, and tested a second time; Group 2 was stored frozen for 3 weeks, thawed,
      and then tested. Each specimen was subjected to 5 cycles of compressive creep
      under 1 MPa for 20 minutes, followed by a 40-minute recovery under no load. After
      testing each specimen was graded on a degeneration scale. A fluid transport model
      was used to parameterize the creep data. RESULTS: There was no statistically
      significant effect of freezing on the elastic or creep response of the discs. The
      degree of pre-existing degeneration had a significant effect on the creep
      response, with the more degenerated discs appearing more permeable. CONCLUSIONS:
      Frozen storage for a reasonable time with a typical method does not significantly
      alter the creep response of human lumbar discs. Freezing may produce subtle
      effects, but these potential artifacts do not appear to alter the discs' time
      dependent behavior in any consequential way. These results may not apply to
      tissue kept frozen for long durations and with poor packaging.

PMID- 11317111
TI  - Mapping the structural properties of the lumbosacral vertebral endplates.
AB  - STUDY DESIGN: A biomechanical investigation using indentation tests in a human
      cadaveric model to seek variation in the structural properties across the lower
      lumbar and sacral endplates. OBJECTIVES: To determine 1) if there are regional
      differences in endplate strength and 2) whether any differences identified are
      affected by spinal level (lumbar spine vs. sacrum) or endplate (superior vs.
      inferior). SUMMARY OF BACKGROUND DATA: It has been postulated that some regions
      of the vertebral body may be stronger than others. Conclusive data, either
      supporting or disproving this theory, would be valuable for both spine surgeons
      and implant designers because one mode of failure of interbody implants is
      subsidence into one or both adjacent vertebrae. METHODS: Indentation tests were
      performed at 27 standardized test sites in 62 bony endplates of intact human
      vertebrae (L3-S1) using a 3-mm-diameter, hemispherical indenter with a test rate
      of 0.2 mm/sec to a depth of 3 mm. The failure load and stiffness at each test
      site were determined using the load-displacement curves. Three-way analyses of
      variance were used to analyze the resulting data. RESULTS: Both the failure load
      and stiffness varied significantly across the endplate surfaces (P < 0.0001),
      with posterolateral regions being stronger and stiffer than the central regions.
      Characteristic distributions were identified in the lumbar superior, lumbar
      inferior, and sacral endplates. The failure load distributions were found to
      differ in 1) the superior lumbar and sacral endplates (P = 0.0077), 2) the
      inferior lumbar and sacral endplates (P = 0.0014), and 3) the superior and
      inferior lumbar endplates (P < 0.0001). The sacral and inferior lumbar endplates
      were both found to be stronger than the superior lumbar endplates (sacrum, P =
      0.054; inferior, P = 0.008) but were not themselves significantly different (P =
      0.89). CONCLUSIONS: Highly significant regional strength and stiffness variations
      were identified in the lumbar and sacral endplates. The center of the bone, where
      implants are currently placed, is the weakest part of the lumbar endplates and is
      not the strongest region of the sacral endplate.

PMID- 11317112
TI  - Active therapy for chronic low back pain part 1. Effects on back muscle
      activation, fatigability, and strength.
AB  - DESIGN: Randomized prospective study of the effects of three types of active
      therapy on back muscle function in chronic low back pain patients. OBJECTIVES: To
      quantify the effects of 3 months active therapy on strength, endurance,
      activation, and fatigability of the back entensor muscles. SUMMARY OF BACKGROUND
      DATA: Many studies have documented an association between chronic low back pain
      and diminished muscular performance capacity. Few studies have quantified the
      changes in these measures following interventions using objective measurement
      techniques or related them to changes in clinical outcome. METHODS: A total of
      148 individuals (57% women) with chronic low back pain (age, 45.0 +/- 10.0 years;
      duration of low back pain, 10.9 +/- 9.5 years) were randomized to a treatment
      that they attended for 3 months: active physiotherapy, muscle reconditioning on
      devices, or low-impact aerobics. Before and after therapy, assessments were made
      of the following: trunk muscle strength (in flexion, extension, lateral bending,
      and axial rotation), erector spinae activation (maximal, and during forward
      bending movements), back extensor endurance (Biering-Sorensen test), and erector
      spinae fatigability (determined from changes in the median frequency of the
      surface electromyographic signal) during isometric and dynamic tests. RESULTS: A
      total of 132 of 148 patients (89%) completed the therapy. Isometric strength in
      each movement direction increased in all groups post-therapy (P < 0.0008), most
      notably in the devices group. Activation of the erector spinae during the
      extension tests also increased significantly in all groups and showed a weak, but
      significant, relationship with increased maximal strength (P = 0.01). Pretherapy
      55% of the subjects showed no relaxation of the back muscles at L5 when in the
      fully flexed position; no changes were observed in any group post-therapy.
      Endurance time during the Biering-Sorensen test increased significantly post
      therapy in all groups (P = 0.0001), but there were no significant changes in EMG
      determined fatigability. Fatigability of the lumbar muscles at L5 (EMG median
      frequency changes) during the dynamic test increased post-therapy (P = 0.0001)
      without group differences. CONCLUSION: Significant changes in muscle performance
      were observed in all three active therapy groups post-therapy, which appeared to
      be mainly due to changes in neural activation of the lumbar muscles and
      psychological changes concerning, for example, motivation or pain tolerance.

PMID- 11317113
TI  - Active therapy for chronic low back pain: part 2. Effects on paraspinal muscle
      cross-sectional area, fiber type size, and distribution.
AB  - DESIGN: Randomized prospective study to compare the effects of three types of
      active therapy on the back muscle structure of chronic low back pain patients.
      OBJECTIVES: To analyze the effects of 3 months active therapy on gross back
      muscle size and muscle fiber type characteristics and their relationship to
      changes in muscle function. SUMMARY OF BACKGROUND DATA: Many studies have
      documented a diminished muscular performance capacity in cLBP patients, but few
      have supported this with evidence of alterations in either the macro- or
      microscopic structure of the paraspinal muscles. Investigations of the changes in
      muscle structure following active rehabilitation are even rarer. METHODS:
      Assessments of trunk muscle cross-sectional area (using MRI), erector spinae
      fiber size/type distribution and pathology (percutaneous biopsy), and muscle
      function (see Part 1) were made in a group of 59 individuals with cLBP, who were
      participating in a randomized trial of active therapies for cLBP (physiotherapy,
      muscle training on devices, aerobics). RESULTS: Fifty-three out of 59 patients
      (90%) completed the therapy. At baseline, significant correlations were observed
      between the size of the paraspinal muscles and isometric back extension strength
      (P=0.0001), and between the proportional area of the muscle occupied by each
      fiber type and the fatigability of the muscle (P=0.012). Following therapy, there
      were small (few percent) increases in trunk muscle size in the aerobics and
      physiotherapy groups and a similarly slight decrease in the devices group.
      Changes in erector spine size correlated only weakly and nonsignificantly with
      changes in back extension strength. There were no major changes in fiber type
      proportion or fiber size in any group following therapy. CONCLUSION: Three months
      active therapy is not sufficient to reverse the typical "glycolytic" profile of
      the muscles of cLBP patients or to effect major changes in backmuscle size. The
      alterations in muscle performance observed (increased strength and endurance;
      Part 1) werenot explainable on the basis of structural changes within the muscle.

PMID- 11317114
TI  - Active therapy for chronic low back pain: part 3. Factors influencing self-rated
      disability and its change following therapy.
AB  - DESIGN: Cross-sectional analysis of the factors influencing self-rated disability
      associated with chronic low back pain and prospective study of the relationship
      between changes in each of these factors and in disability following active
      therapy. OBJECTIVES: To examine the relative influences of pain, psychological
      factors, and physiological factors on self-rated disability. SUMMARY OF
      BACKGROUND DATA: In chronic LBP, the interrelationship between physical
      impairment, pain, and disability is particularly complicated, due to the
      influence of various psychological factors and the lack of unequivocal methods
      for assessing impairment. Investigations using new "belief" questionnaires and
      "sophisticated" performance tests, which have shown promise as discriminating
      measures of impairment, may assist in clarifying the situation. Previous studies
      have rarely investigated all these factors simultaneously. METHODS: One hundred
      forty-eight patients with cLBP completed questionnaires and underwent tests of
      mobility, strength, muscle activation, and fatigability, and (in a subgroup)
      erector spinae size and fiber size/type distribution. All measures were repeated
      after 3 months active therapy. Relationships between each factor and self-rated
      disability (Roland and Morris questionnaire) at baseline, and between the changes
      in each factor and changes in disability following therapy, were examined.
      RESULTS: Stepwise linear regression showed that the most significant predictors
      of disability at baseline were, in decreasing order of importance: pain;
      psychological distress; fear-avoidance beliefs; muscle activation levels; lumbar
      range of motion; gender. Only changes in pain, psychological distress, and fear
      avoidance beliefs significantly accounted for the changes in disability following
      therapy. CONCLUSION: A combination of pain, psychological and physiological
      factors was best able to predict baseline disability, although its decrease
      following therapy was determined only by reductions in pain and psychological
      variables. The active therapy program-in addition to improving physical function
      appeared capable of modifying important psychological factors, possibly as a
      result of the positive experience of completing the prescribed exercises without
      undue harm.

PMID- 11317115
TI  - Osteoporosis.

PMID- 11317116
TI  - Evaluation of carriers of bone morphogenetic protein for spinal fusion.
AB  - STUDY DESIGN: Posterolateral lumbar transverse process fusion in a rabbit model
      was performed using two different carriers for recombinant human morphogenetic
      protein-2, one having a porous structure and the other being a Type I collagen
      sheet. OBJECTIVES: To compare the effectiveness of two different carriers for
      recombinant human morphogenetic protein-2 in achieving lumbar intertransverse
      process arthrodesis. SUMMARY OF BACKGROUND DATA: The application of
      osteoinductive growth factors at various anatomic sites, such as in long bones
      and spinal segments, has been performed experimentally by many researchers.
      Although many carriers of osteoinductive factors have been reported, the most
      effective carrier has not been established. We have reported the efficacy of
      sintered bovine bone, True Bone Ceramics, which is coated with Type I collagen as
      a carrier of recombinant human bone morphogenetic protein-2 in achieving lumbar
      intertransverse process arthrodesis. True Bone Ceramics is a crystallized form of
      bone minerals made from sintering bovine bone at high temperatures and possesses
      natural trabecular structure. The crystalline character of True Bone Ceramics is
      similar to that of artificial hydroxyapatite. In this study we focused on the
      structure of two different carriers to facilitate osteosynthesis in lumbar
      arthrodesis. METHODS: Fifty-four adult rabbits underwent bilateral lumbar
      intertransverse process arthrodesis at L4-L5. The animals were divided into five
      groups and had implants placed as follows: Group 1, autograft group, harvested
      autologous corticocancellous bone from the posterior iliac crest; Group 2, TBC
      group, True Bone Ceramics alone; Group 3, TBC-TBMP group, True Bone Ceramics
      coated with Type I collagen infiltrated with 100 microg of recombinant human bone
      morphogenetic protein-2; Group 4, collagen group, Type I collagen sheet; and
      Group 5, collagen-BMP group, implanted collagen sheet containing 100 microg of
      recombinant human bone morphogenetic protein-2. Spinal fusion was evaluated by
      radiographic analysis, manual palpation, biomechanical testing, and histologic
      examination at both 3 and 6 weeks after surgery. RESULTS: Radiographs in the TBC
      TBMP group showed a continuous trabecular pattern within the intertransverse area
      at 3 weeks after surgery. The fusion mass in the intertransverse area was more
      prominent than in the other groups. At 3 weeks after surgery the TBC-TBMP group
      had higher fusion rates based on manual palpation, and the fusions showed
      significantly higher tensile strength and stiffness. The histologic findings in
      the TBC-TBMP group at 3 weeks after surgery showed a cortical bone rim around the
      edge of the fusion mass, and contiguous new bone appearing between the recipient
      bone and the matrix of TBC without evidence of foreign body formation. In the
      collagen-BMP group, less mature bone formation was present within the grafted
      area and the new bone was not contiguous, even at 6 weeks after surgery.
      CONCLUSIONS: As a carrier for recombinant human bone morphogenetic protein-2,
      True Bone Ceramics, possessing a bony or porous structure, was more effective
      than a Type I collagen sheet in achieving a faster and stronger lumbar spinal
      fusion in a rabbit model.

PMID- 11317117
TI  - Effect of nucleus pulposus on the neural activity of dorsal root ganglion.
AB  - STUDY DESIGN: This study was designed to investigate, using neurophysiologic
      techniques in an in vivo rat model, the effect of application of nucleus pulposus
      to the nerve root on the neural activity of the dorsal root ganglion and the
      corresponding receptive fields. OBJECTIVES: To assess a further role of the
      dorsal root ganglion in mechanisms of radicular pain in lumbar disc herniation.
      SUMMARY OF BACKGROUND DATA: It has been suggested that the epidural application
      of autologous nucleus pulposus without mechanical compression causes nerve root
      inflammation and related radicular pain in lumbar disc herniation. Concerning the
      dorsal root ganglion, its mechanical hypersensitivity and potential for
      generating ectopic discharges have been reported. However, the effect of
      autologous nucleus pulposus on the dorsal root ganglion is uncertain. METHODS: In
      adult Sprague-Dawley rats spontaneous neural activity was recorded from the
      surgically exposed L5 dorsal root using electrophysiologic techniques, and the
      mechanosensitivity of L5 dorsal root ganglia and corresponding receptive fields
      on the hind paw were measured using calibrated nylon filaments. Autologous
      nucleus pulposus from the tail or fat was implanted at the L5 nerve root. Neural
      activity was monitored for 6 hours. RESULTS: Spontaneous neural activity in the
      nucleus pulposus group gradually increased and showed significant differences
      compared with the fat group from 2.5 to 6 hours after exposure. The
      mechanosensitivity of the dorsal root ganglia showed significant increases
      compared with the fat group. CONCLUSIONS: After application of nucleus pulposus
      to the nerve root, the dorsal root ganglion demonstrated increased excitability
      and mechanical hypersensitivity. These results suggest that nucleus pulposus
      causes excitatory changes in the dorsal root ganglion.

PMID- 11317119
TI  - Sensory innervation of the dorsal portion of the lumbar intervertebral discs in
      rats.
AB  - STUDY DESIGN: The levels of dorsal root ganglions (DRGs) innervating the dorsal
      portion of the lumbar intervertebral discs from L1-L2 to L4-L5 were investigated
      in rats by the retrograde transport method. The pathways and functions of nerve
      fibers supplying the dorsal portion of the discs were investigated by denervation
      and immuno-histochemistry. OBJECTIVES: To investigate the sensory innervation of
      the dorsal portion of the lumbar intervertebral discs in rats. SUMMARY OF
      BACKGROUND DATA: The dorsal portion of the L5-L6 disc has been reported to be
      innervated multisegmentally, and anesthetic blockade of the paravertebral
      sympathetic trunks and the L2 spinal nerve can relieve discogenic low back pain.
      However, sensory innervation of the dorsal portion of the lumbar discs at other
      levels has not been clarified. METHODS: A retrograde transport of Fluoro-Gold was
      used. We studied a nonsympathectomy group (n = 44) and a sympathectomy group (n =
      50) in which paravertebral sympathetic trunks were resected from L1 to L5 levels.
      Using a ventral approach, Fluoro-Gold crystals were inserted into the dorsal
      portion of the L1-L2, L2-L3, L3-L4, and L4-L5 discs. Seven days after surgery,
      Fluoro-Gold-labeled neurons were counted in the bilateral dorsal root ganglions
      from T10 to L6. RESULTS: Fluoro-Gold-labeled neurons were distributed in dorsal
      root ganglions from T11 to L5 levels in the nonsympathectomy group. However, in
      the sympathectomy group the number of labeled neurons was less than that of the
      nonsympathectomy group in T11, T12, and T13 dorsal root ganglions of the L1-L2
      disc group, in T12, T13, and L1 dorsal root ganglions of the L2-L3 disc group, in
      T12, T13, L1, and L2 dorsal root ganglions of the L3-L4 disc group, and in T12,
      T13, L1, and L2 dorsal root ganglions of the L4-L5 disc group. CONCLUSION: The
      dorsal portion of the lumbar discs from L1-L2 to L4-L5 is multisegmentally
      innervated by the T11 through L5 dorsal root ganglions. Sensory fibers from the
      upper dorsal root ganglions innervate the dorsal portion of the discs via the
      paravertebral sympathetic trunks, although those from the lower dorsal root
      ganglions innervate via the sinuvertebral nerves. Furthermore, sensory nerve
      fibers enter the paravertebral sympathetic trunks through the corresponding ramus
      communicans and reach the dorsal root ganglions via each ramus communicans at the
      L2 and/or more cranial levels.

PMID- 11317120
TI  - Effect of endplate conditions and bone mineral density on the compressive
      strength of the graft-endplate interface in anterior cervical spine fusion.
AB  - STUDY DESIGN: Destructive compression tests and finite element analyses were
      conducted to investigate the biomechanical strength at the graft-endplate
      interface in anterior cervical fusion. OBJECTIVES: To investigate the effect of
      endplate thickness, endplate holes, and bone mineral density of the vertebral
      body on the biomechanical strength of the endplate-graft interface in an anterior
      interbody fusion of the cervical spine. SUMMARY OF BACKGROUND: Subsidence of the
      graft into the vertebral body is a well-known complication in anterior cervical
      fusion. However, there is no information in the literature regarding the
      compressive strength of the graft-endplate interface in relation to the endplate
      thickness, holes in the endplate, and bone mineral density of the vertebral body.
      METHODS: Biomechanical destructive compression tests and finite element analyses
      were performed in this study. Cervical vertebral bodies (C3-C7) isolated from
      seven cadaveric cervical spines (age at death 69-86 years, mean 79 years) were
      used for compression tests. Bone mineral density of each vertebral body was
      measured using a dual energy radiograph absorptiometry unit. Endplate thickness
      was measured using three coronal computed tomography images of the middle portion
      of the vertebral body obtained using a computer-assisted imaging analysis. Then
      each vertebral body was cut into halves through the horizontal plane. A total of
      54 specimens, consisting of one endplate and half of the vertebral body, were
      obtained after excluding eight vertebrae with gross pathology on plain
      radiograph. Specimens were assigned to one of three groups with different
      endplate conditions (Group I, intact; Group II, partial removal; and Group III,
      complete removal) so that group mean bone mineral density became similar. Each
      endplate was slowly compressed until failure using an 8-mm-diameter metal
      indenter, and the load to failure was determined as a maximum force on a recorded
      force-displacement curve. The effect on the strength of the graft-endplate
      interface of various hole patterns in the endplate was studied using a finite
      element technique. The simulatedhole patterns included the following: one large
      central hole, two lateral holes, two holes in the anterior and posterior portion
      of the endplate, and four holes evenly distributed from the center of the
      endplate. Stress distribution in the endplate was predicted in response to an
      axial compressive force of 110 N, and the elements with von Mises stress greater
      than 4.0 MPa were determined as failed. RESULTS: The endplate thickness and bone
      mineral density were similar at all cervical levels, and the superior and
      inferior endplates had similar thickness at all cervical levels. There was no
      significant association between bone mineral density and endplate thickness. Load
      to failure was found to have a significant association with bone mineral density
      but not with endplate thickness. However, load to failure tends to decrease with
      incremental removal of the endplate, and load to failure of the specimens with an
      intact endplate was significantly greater than that of the specimens with no
      endplate. Finite element model predictions showed significant influence of the
      hole pattern on the fraction of the upper endplate exposed to fracture stress. A
      large hole was predicted to be more effective than the other patterns at
      distributing a compressive load across the remaining area and thus minimizing the
      potential fracture area. CONCLUSION: Results of this study suggest that it is
      important to preserve the endplate as much as possible to prevent graft
      subsidence into the vertebral body, particularly in patients with poor bone
      quality. It is preferable to make one central hole rather than multiple smaller
      holes in the endplate for vascularity of the bone graft because it reduces the
      surface area exposed to fracture stresses.

PMID- 11317121
TI  - An experimental study on the interface strength between titanium mesh cage and
      vertebra in reference to vertebral bone mineral density.
AB  - STUDY DESIGN: Using human cadaver spines, the authors investigated mechanical
      properties of the interface between titanium mesh cage and vertebra in respect to
      vertebral bone mineral density. OBJECTIVES: The objective of this study is to
      examine the effects of the size of the mesh cage and an internal end ring system
      on interface mechanical properties in reference to vertebral bone mineral
      density. SUMMARY OF BACKGROUND DATA: A titanium mesh cage has recently been
      developed for anterior spinal reconstruction. The cage provides immediate
      postoperative stability and facilitates bony union with cancellous bone packed in
      the cage itself. Mechanical properties of the interface between the cage and
      vertebra, however, are yet to be clarified in osteoporotic spine. METHODS: Twenty
      five lumbar vertebrae harvested from embalmed human cadavers (n = 20) were used.
      The vertebrae were divided into four experimental groups according to the applied
      cage conditions: Phi25 mm cage without internal end ring (L-), Phi19 mm cage
      without internal end ring (S-), Phi25 mm cage with internal end ring (L+), and
      Phi19 mm cage with internal end ring (S+). Bone mineral density of whole
      vertebral body was measured by dual energy radiograph absorptiometer (DXA).
      Peripheral quantitative computed tomography was used to determine local bone
      mineral density of subchondral cancellous bone of vertebral body. Each cage was
      compressed on vertebral endplate via a specially designed device connected to a
      material testing machine. Maximum load and stiffness of the interface between the
      cage and vertebra were measured from load-deformation data in quasi-static
      compression loading with a loading rate of 0.5 mm/min. Relationships between the
      mechanical properties and vertebral bone mineral densities were evaluated. In 11
      specimens acoustic emission during compression loading was measured and
      simultaneously recorded in load-deformation data. After the mechanical test
      microradiograms of midsagittal sections of the vertebrae were taken to observe
      failure patterns of endplate or trabecular bone. RESULTS: Vertebrae compressed
      with large cages (group: L- or L+) showed greater maximum load than those
      compressed with small cages (group: S- or S+). The internal end ring contributed
      to higher maximumload. The size of the cage or the internal end ring, however,
      did not have any effect on stiffness. Maximum load and stiffness were positively
      correlated with whole vertebral bone mineral density measured by dual energy
      radiograph absorptiometer or local cancellous bone mineral density of subchondral
      bone measured by peripheral quantitative computed tomography. Correlation
      coefficient and P value were more significant in the association of the
      mechanical properties and subchondral bone mineral density measured by peripheral
      quantitative computed tomography than in the association of the parameters and
      whole vertebral bone mineral density measured by DXA. A load-deformation curve
      with an acoustic emission event count rate showed that significant acoustic
      emission signals were generated around maximum load. On microradiographic study
      most vertebrae compressed with the cage showed encroachment of the cage spikes
      into the endplate or trabecular structure, preserving structures of the most
      central portion of the vertebrae. CONCLUSION: A titanium mesh cage with larger
      diameter and/or augmentation of internal end ring produces a significant increase
      of the interface strength between the cage and the vertebra. A positive
      correlation between the interface strength and vertebral bone mineral density
      suggests that vertebral bone mineral density is an important parameter for
      successful spinal reconstruction, and also implies that in severe osteoporotic
      spine the stability of the cage is declined, and other instrumentation should be
      combined.

PMID- 11317122
TI  - Effects of gender and age differences on the distribution of bone content in the
      third lumbar vertebra.
AB  - STUDY DESIGN: A cross-sectional study on the distribution of bone mineral content
      in the third lumbar vertebrae. OBJECTIVES: To evaluate the effects of age and
      gender on the distribution of bone mineral content in the third lumbar vertebrae.
      SUMMARY OF BACKGROUND DATA: Compression fractures occur mainly at the vertebral
      body. Variations in the distribution of bone mass in a vertebra, if undefined,
      may bias the ability of the acquired bone mineral density values, which was
      usually measured posteroanteriorly, to predict the risk of fractures. METHODS:
      The bone mineral content of the whole L3, including the L3 vertebral body and the
      posterior segment, was measured using a lateral approach with a dual energy
      radiograph absorptiometer on 177 healthy Taiwanese adults including 65 men and 55
      premenopausal and 57 postmenopausal women. RESULTS: The proportion of bone
      mineral content in the vertebral body was significantly lower in premenopausal
      women than in age-matched men (39.1 +/- 0.9% vs. 50.0 +/- 1.7%, P < 0.0001).
      Furthermore, whereas postmenopausal women showed a decreased proportion of bone
      mineral content in the vertebral body with increased age (about -0.0022 per year,
      P = 0.0001), premenopausal women and men showed a sustained proportion.
      CONCLUSIONS: The proportion of bone mineral content distributed in the body of L3
      vertebrae was lower in women than in men. The discrepancy of this parameter
      between the genders was even larger with increased ages.

PMID- 11317123
TI  - Patient outcome after resection of lumbar juxtafacet cysts.
AB  - STUDY DESIGN: Retrospective review of patients who underwent lumbar juxtafacet
      cyst resection with questionnaire follow-up. OBJECTIVES: Determine the long-term
      outcome after resection of lumbar juxtafacet cysts. SUMMARY OF BACKGROUND DATA:
      Juxtafacet cysts are uncommon causes of radicular pain and are often associated
      with significant spinal degenerative disease. Previous studies have not focused
      on the outcome of patients who have undergone resection. METHODS: Charts of 29
      patients who underwent lumbar juxtafacet resection were reviewed and an outcomes
      questionnaire was sent to each. RESULTS: Thirty-three lumbar juxtafacet cysts
      were resected from 29 patients. Cysts, 31 (94%) from facets and 2 (6%) from the
      ligamentum flavum, most commonly arose at the L4-L5 level (51%). Twelve patients
      (41%) were found to have some degree of spondylolisthesis before surgery, while
      26 patients (90%) had facet arthropathy. Two patients (7%) underwent concurrent
      resection and fusion. Recurrence occurred in 3%. Three patients (9%) had
      subsequent lumbar spine operations, including 2 fusions (6%). Incidental durotomy
      was the most common surgical complication occurring in 3 cases (9%). Twenty-four
      patients (83%) responded to follow-up questionnaire or phone interview. Mean
      length of follow-up was 24 months (4-64 months). Twenty patients (83%) reported
      improvement in pain, and 16 (67%) reported an improved level of function. All
      respondents reported some degree of improvement in their condition after surgery.
      CONCLUSIONS: Juxtafacet cysts are an uncommon cause of radiculopathy. Surgical
      resection is the treatment of choice with low rates of complications,
      recurrences, and residual complaints.

PMID- 11317124
TI  - Long-term complications in adult spinal deformity patients having combined
      surgery a comparison of primary to revision patients.
AB  - STUDY DESIGN: This is a comparison of primary (N = 18) to revision (N = 26)
      combined (anterior and posterior surgery) adult spinal deformity patients with
      regard to late (>6 months) complications and radiographic/functional outcomes at
      a minimum 2-year follow-up. OBJECTIVES: To determine whether revision status
      increases the risk of late complications or offers a poor prognosis for
      functional outcome in adult deformity patients. SUMMARY OF BACKGROUND DATA: It is
      known that patients who have combined surgery for adult deformity have a high
      incidence of perioperative complications. Long-term complications and the effect
      of revision status have not been clarified in the literature. The functional
      outcomes for these patients are unclear as to whether or not there is a
      difference between primary and revision patients. Outside the arena of adult
      spinal deformity the functional outcomes for revision cases have been
      disappointing. METHODS: A consecutive series of 44 patients who underwent
      combined procedures for adult spinal deformity were followed for a minimum of 2
      years (average follow-up 42 months). Clinical data were obtained by chart and
      radiographic review. Major complications were considered to be deep wound
      infection, pseudarthrosis, transition syndrome, neurologic deficit, and death.
      Minor complications considered were asymptomatic instrumentation failure (without
      loss of correction), instrumentation prominence requiring removal, and proximal
      or distal junctional segmental kyphosis (5-10 degrees ) or subsequent disc space
      narrowing of 2-5 mm without clinical symptoms. The patients also completed the
      AAOS Lumbar/Scoliosis MODEMS questionnaires aimed at assessing pain, function,
      and satisfaction. RESULTS: Minor complications were comparable in both groups: 4
      of 18 (22%) in the primary group and 6 of 26 (23%) in the revision group. Major
      complications were slightly more frequent in the primary group with five
      complications in 4 patients (4 of 18 patients) (22%) compared with 3 of 26
      patients (12%) in the revision group. The incidence of pseudarthrosis was 22% (4
      of 18) for the primary group and 4% (1 of 26) for the revision group (P< 0.14).
      Forty of 44 patients completed the questionnaires. The primary patients
      functioned at a slightly higher level after surgery than the revision group. The
      level of pain was also slightly lower at final follow-up in the primary group.
      Despite these differences, the revision group had a higher level of patient
      satisfaction. CONCLUSION: At a minimum 2-year follow-up the late complications
      were not higher in the revision patients than in the primary group. The rate of
      major long-term complications, specifically pseudarthroses, was higher in the
      primary group. Patient satisfaction was higher in the revision patients, probably
      because they were experiencing a greater level of perceived pain and dysfunction
      at the time of their reconstruction.

PMID- 11317125
TI  - Electrochemical measurement of transport into scoliotic intervertebral discs in
      vivo using nitrous oxide as a tracer.
AB  - STUDY DESIGN: An in vivo study measuring nitrous oxide concentrations in
      scoliotic intervertebral discs during surgery. OBJECTIVES: To determine pathways
      for nutrient transport into scoliotic human discs in vivo. SUMMARY OF BACKGROUND
      DATA: The intervertebral disc is the largest avascular structure in the body.
      Disc cells in the nucleus rely on the blood supply from the vertebral bodies for
      supply of nutrients and removal of waste. Loss of nutrient supply is thought to
      lead to disc degeneration, but solute transport has not been measured in vivo in
      humans. METHODS: We measured solute transport into the disc using N2O as a
      tracer, in 19 human discs from five patients with neuromuscular scoliosis (6-19
      years of age) during surgery for correction of scoliotic deformities. During
      anesthesia N2O diffuses into the disc at a rate governed by effective
      permeability of the vertebral body-disc interface. Intradiscal N2O concentrations
      were measured amperometrically using silver needle microelectrodes, which were
      inserted into the discs once they were exposed by an anterior approach. RESULTS:
      For all spines N2O concentrations were very low in the disc at the curve apex (6%
      those expected from unimpeded diffusion) and, although still low, were
      significantly higher 2 discs below or above the apex. CONCLUSIONS: Because flux
      into the apical disc is most restricted, the decrease in solute transport is
      possibly induced by changes in mechanical stress on the disc; microfocal
      radiographs of a scoliotic spine suggest that increased endplate calcification
      could be partly responsible for limiting solute diffusion.

PMID- 11317126
TI  - Unknown case. Diagnosis: facet joint septic arthritis T12-L1 on the left with
      extension of the infection into the spinal canal producing a large epidural
      abscess.

PMID- 11317127
TI  - Mislabelling the articles, and then injecting strong bias against lumbar
      provocation discography as a diagnostic tool.

PMID- 11317128
TI  - Re: we have misunderstood the purpose of a Cochrane Library Review.

PMID- 11317129
TI  - Side of symptomatic annular tear and site of low back pain: is there a
      correlation?
AB  - STUDY DESIGN: A retrospective chart review. OBJECTIVES: To report the correlation
      between the side of a concordantly painful, post-discography computer tomography
      (CT) visualized, annular tear, and the side of a patients' low back pain. SUMMARY
      OF BACKGROUND DATA: An annular fissure extending from the nucleus to the outer
      one-third of the annulus is thought to be the nociceptive source stimulated
      during provocative lumbar discography. To our knowledge, there are no studies
      that have attempted to delineate whether the side of the annular tear correlates
      with the side of the patient pain. METHODS: One hundred and one post-discography
      CT scans, performed on patients with single level, concordantly painful, and
      fissured discs identified during lumbar discography, were randomly obtained from
      the archived and current files of the Penn Spine Center's film library. These
      were reviewed by both the lead author and a spine radiologist, both of who were
      blinded to the side of the patients pain, to determine which scans demonstrated
      clearly definable tears extending to the outer one-third of the annulus.
      Statistical analysis via the exact method was used to determine the correlation
      between the side of the patients tear and the side of the patients pain. RESULTS:
      Forty post-discography CT scans met the inclusion criteria. There was a random
      correlation between the side of the patients concordantly painful annular tear
      and the side of the patients pain. CONCLUSIONS: The results of this study raise
      several questions regarding the embryologic development of the intervertebral
      disc and its somite, neurologic transmission of discogenic pain, distribution of
      chemical inflammagens, validity of discography, technique of ESI, and technique
      and validity of IDET.

PMID- 11317131
TI  - [Duodenal ulcer and Helicobacter pylori].
AB  - BACKGROUND: The purpose of this study was to evaluate the relationship between
      duodenal ulcer (DU), Helicobacter pylori (Hp) infection and genetic and
      enviromental factors, and its influence on treatment and long-term RESULTS.
      METHOD: In the course of an epidemiological study on the prevalence of
      esophagogastroduodenal diseases, 1,169 volunteers underwent an endoscopy of the
      upper part of the gastrointestinal tract. The relationship of incidence rate and
      size of duodenal ulcers and several risks factors was investigated. RESULTS: A DU
      was observed in 240 subjects (20.5%), mostly of male gender (64.4% - p<0.0001).
      The Histological presence of a gastric Hp infection was confirmed in 179 cases
      (74.6%); it did not influenced the mean size of the ulcers and the presence of
      gastric intestinal metaplasia, compared to subjects without Hp infection.
      However, a superficial chronic gastritis was observed in 95.9% of Hp+ subjects
      and in 83.3% of Hp- (p<0.003), whereas a familiar history of DU was noted in
      33.3% of Hp+ subjects and in 50.8% of Hp- (p<0.02). The main risk factor for DU
      was represented by Hp infection in 119 cases (49.6%), by infective and genetic
      factors in 60 cases (25%) and only by the genetic factor in 31 cases (12.9%), and
      was not detected in 30 cases (12.5%). Ulcer recurrence rates, after medical
      therapy, were 0,5% and 6.5% (p<0.03) at a 2-month follow-up, and 2.2% and 49.1%
      (p<0.00001) at a 12-month follow-up, among Hp+ and Hp- patients, respectively.
      CONCLUSIONS: The most common risk factor for DU was a gastric Hp infection, alone
      or associated to the genetic factor. Since the high incidence of recurrences at a
      12-month follow-up, patients affected with a DU but Hp- represented an important
      therapeutic concern.

PMID- 11317132
TI  - [Prevalence of dyspepsia in liver cirrhosis: a clinical and epidemiological
      investigation].
AB  - BACKGROUND: To evaluate the prevalence and severity of dyspepsia in patients with
      liver cirrhosis. METHODS: A questionnaire was distributed to 33 consecutive
      patients suffering from liver cirrhosis (22 males and 11 females, mean age 65.5
      years; 24 with post-hepatitis liver cirrhosis and 9 with alcohol- based
      cirrhosis) to evaluate dyspeptic symptoms. Patients receiving prolonged treatment
      at home with anti-acid drugs immediately prior to hospitalisation were excluded
      from the study. RESULTS: Twenty-eight patients complained of dyspeptic disorders.
      An organic cause of symptoms could not be identified in 8 patients (24.2%),
      whereas the following were identified as the causes of organic dyspepsia in the
      remaining 20 patients, in order of frequency: gastroesophageal reflux disease
      (55%), congestive gastropathy (40%), gastric or duodenal ulcer (30%) and
      gallbladder stones (35%). Lastly, a combination of at least two of these morbid
      conditions was found in 10 patients (50%). The severity of dyspeptic symptoms was
      similar in both organic and functional forms; symptoms tend to occur with
      moderate intensity, worsening in parallel with the aggravation of liver disease.
      CONCLUSIONS: Dyspepsia is a very frequent phenomenon in cirrhotic patients; it is
      normally sustained by an organic cause. The predominance of functional forms in
      liver cirrhosis is practically the same as that reported in the general
      population.

PMID- 11317133
TI  - [Pseudothrombocytopenia: clinical comment on 37 cases].
AB  - BACKGROUND: Pseudothrombocytopenia (PTCP) is characterized by in vitro EDTA-, pH
      , temperature- and time-dependent clumping which gives rise to spurious
      piastrinopenia at platelet count in automatized analyzers. It is caused by serum
      immunoglobulins recognizing some cryptoantigens on the platelet surface membrane.
      Aim of this study was to evaluate the prevalence of PTCP in a series of patients
      and its clinical significance. METHODS: From all the inpatients, in Internal
      Medicine Division, during 29 months, we have considered as PTCP the
      thrombocytopenias persistent in EDTA and contemporaneously, missing with ACD at
      the automatized counter, after microscopic examination. Then we estimated: PTCP
      rate in regard to all patients, sex, age and morbid associations both in PTCP
      group and in all patients. These frequences were compared with the chi-square
      test. RESULTS: 37 cases of PTCP are observed from a cohort of 2922 inpatients
      (1.26%): 23 were males, 17 females; median age was 73.7+/-11.2. The frequency of
      the following associations was significantly higher in the PTCP group: solid
      tumors in 9/37 (24.3%), myelo- and lymphoproliferative syndromes in 7/37 (18.9%),
      autoimmune disease in 4/37 (10.8%). CONCLUSIONS: This study suggests that PTCP is
      one of the more frequent thrombocytopenias: it is important to identify it, to
      avoid clinical and therapeutic mistakes. Moreover PTCP, in our study, is often
      correlated with important diseases. We can conclude that in hospitalized old
      patients, PTCP could represent a signal to search more severe illnesses.

PMID- 11317134
TI  - Correlation between family history of hypertension and haemostatic disorders.
AB  - BACKGROUND: The aim of this study was to evaluate whether a family history of
      hypertension is associated with haemostatic disorders. METHODS: In 38
      normotensive subjects with a family history of hypertension (relatives) and in 46
      sex, age and body mass index matched controls with no family history of
      hypertension, tissue-type plasminogen activator (t-PA), plasminogen activator
      inhibitor (PAI-1), D-dimer (DD) and prothrombin fragment 1+2 (F1+2) were
      evaluated. RESULTS: The t-PA and PAI-1 observed values were significantly higher
      than the values detected in the controls. CONCLUSIONS: These data seem to suggest
      a correlation between family history of hypertension and haemostatic disorders.

PMID- 11317135
TI  - Blood reduced glutathione (GSH) concentrations in healthy and ill subjects.
AB  - BACKGROUND: Recently blood reduced glutathione (GSH), an important cellular
      antioxidant, has been proposed as an indicator of health, particularly in the
      elderly. To date, a gold standard unit for the expression of GSH concentrations
      is not known. The aim of the study is to define the most sensitive laboratory
      expression of GSH. METHODS:  EXPERIMENTAL DESIGN: a comparative study among some
      laboratory expressions of GSH. SETTING: Geriatric and Internal Medicine Units;
      General Community. PATIENTS AND PARTICIPANTS: forty-eight inpatients from
      Geriatric and Internal Medicine Units and 82 healthy subjects recruited among
      medical students and residents, people from preventive medicine services and from
      local senior centres. EXCLUSION CRITERIA FOR HEALTHY SUBJECTS: use of drugs in
      the year prior to the study. INTERVENTIONS: neither treatment nor interventions.
      MEASURES: the laboratory expression of GSH, compared in this study, were mg/dl,
      packed cell volume (PCV), mg/1010 RBC, mM/gHb. RESULTS: We noted statistically
      significant differences only if GSH was calculated as mg/1010 RBC; higher values
      were found in healthy subjects than in inpatients, apart from age. This modality
      of expression is minimally affected by haematological parameters; the low
      sensibility of the other modalities may be due to variations of MCV and Hb.
      Instead, the ratio GSH mg/1010 RBC expresses the true GSH concentrations inside
      each erythrocyte. This modality of expression is minimally affected by
      haematological parameters; the low sensibility of the other modalities may be due
      to variations of MCV and Hb.

PMID- 11317136
TI  - [Reliability of a polymerase chain reaction (PCR) technique in the diagnosis of
      Lyme borreliosis].
AB  - BACKGROUND: The Polymerase Chain Reaction (PCR) technique has some application
      limits therefore suggesting the evaluation of the sensibility (SE), specificity
      (SP), predictive positive value (PPV) and predictive negative value (NPV) of a
      PCR test detecting a target sequence of OspA gene of Borrelia burgdorferi sensu
      lato. This technique is currently used in the diagnosis of Lyme borreliosis in
      our laboratory. METHODS: Ninety-three patients, either examined in our outpatient
      clinic or coming from other clinical centres, were divided in two groups on the
      basis of a correlation between clinical picture and serologic tests (ELISA and
      Western Blot): 42 patients were true positives (tp) and 51 true negatives (tn).
      The samples (77 sera, 16 cerebrospinal fluids) have been tested with the above
      PCR technique. The results obtained were used to calculate the SE, SP, PPV and
      NPV. Subsequently, 13 urine samples of patients with negative serum PCR were
      examined with the same technique. RESULTS: A high SP and a low SE, high PPV and a
      considerably lower NPV have been reported. 50% of the PCR positive results,
      obtained with serum and cerebrospinal fluid samples corresponded to patients who
      were true positives at clinical examination but negatives at serologic tests.
      62.5% of urine samples positive results belonged to tp patients who had negative
      serologic and serum PCR RESULTS. CONCLUSIONS: The obtained results suggested a
      good reliability of positive results obtained with the PCR technique used in this
      study and allowed the false negatives of serologic tests to be detected, more
      specifically when urine samples were used.

PMID- 11317137
TI  - Mixed cryoglobulinemia and hepatitis C virus infection.
AB  - The striking association between hepatitis C virus (HCV) infection and mixed
      cryoglobulinemia (MC) has conducted to the hypothesis that HCV plays a major role
      in the production of MC. MC is a systemic vasculitis characterized by the
      presence in the serum of cryoprecipitable immunoglobulins (Ig), with rheumatoid
      factor (RF) activity. HCV which is both a hepatotropic and lymphotropic virus,
      has been proposed as a causative agent of MC, and is responsible for clinic
      manifestations such as glomerulonephritis, vasculitis, neuropathy. Because MC
      evolves frequently into B-cell non-Hodgkin lymphoma (NHL), chronic HCV infection
      has been proposed as an aetiologic factor in B-cell lymphoma. Several controlled
      trials have demonstrated that combined therapy with interferon and ribavirin is
      beneficial in chronic hepatitis C with and without MC. Several studies have also
      suggested that interferon alpha or association of corticosteroids and or
      ribavirin to the interferon alpha regimen can attenuate the clinical
      manifestations of MC and considerably reduce CG production. Different situations
      can be encountered which may modify treatment strategies: patients may be
      asymptomatic carriers of cryoglobulins but may have chronic hepatitis according
      to usual criteria, in some cases, cryoglobulinemic patients have no active liver
      disease, with normal alanine amino transferase and mild liver lesions at liver
      biopsy, but severe manifestations of MC, in other patients, active liver disease
      and MC related symptoms are both present.

PMID- 11317138
TI  - [POEMS syndrome].
AB  - The POEMS syndrome is a rare multisystem disorder of obscure pathogenesis
      characterized by polyneuropathy, organomegaly, endocrinopathy of various forms,
      production of monoclonal component, and skin changes. This syndrome occurs only
      in about 1% of plasmocytoma cases, but in more than 50% of the rare
      osteosclerotic subtypes and plasma cell dyscrasias. Therefore it is frequently
      associated with multicentric Castleman's disease. Chronically elevated serum
      levels of proinflammatory cytokines associated with a weak or even decreased of
      anti-inflammatory cytokines, is a feature of this syndrome. Recently, the
      overproduction of serum vascular endothelial growth factor may be relevant to the
      pathogenesis of most the manifestations including neuropathy.

PMID- 11317139
TI  - [Sweet syndrome: personal experience and review of the literature].
AB  - The Sweet's syndrome or acute febrile neutrophilic dermatosis is a well
      characterized cutaneous disease frequently associated with inflammatory and
      neoplastic diseases, particularly haematologic malignancies, and usually precedes
      the underlying disorders for months or years. Much of the evidence for this is
      based on case reports, small series of cases and reviews of the literature.
      Recently, immunologic theories suggest that the pathogenesis of Sweet's syndrome
      is probably mediated through helper T cell type 1 cytokines (IL-2, gammaINF)
      rather than helper T cell type 2 cytokines (IL-4). This results in the
      stimulation of a cytokine cascade, which might be responsible for the local and
      systemic activation of neutrophils and histiocytes. Clinically, Sweet's syndrome
      is characterized by the acute onset of an eruption of painful erythematous or
      violaceous plaques or nodules with fever, malaise, neutrophil leucocytosis and a
      raised erythrocyte sedimentation rate. Personal experience in 4 cases observed
      during five years is described. All of them presented diagnostic criteria of this
      disease and had a good response to corticotherapy and/or indomethacin. A review
      of the literature on this uncommon syndrome is also reported.

PMID- 11317140
TI  - Molecular characterization of a rare hemoglobin variant: Hb-Hinsdale:
      beta139(H17)ASN-->Lys.
AB  - The authors describe the characteristics of a rare hemoglobin mutant found in a
      young female. She carries the aminoacid replacement of Hb
      Hinsdale:beta139(H17)ASN-->Lys, which was identified at molecular level. This
      case, clinically and hematologically symptomless, is identical, but genetically
      independent, to the cases first described in an American family.

PMID- 11317141
TI  - [Treatment of chronic arterial occlusive disease of the lower limbs with
      propionyl-1-carnitine in elderly patients].
AB  - BACKGROUND: Atherosclerosis is the most common pathology affecting the arterial
      system in elderly patients and arterial occlusive disease of the lower limbs
      represents one of the most severe complications. Intermittent claudication is the
      clinical expression of the ischemia underlying this arterial disease. Patients
      suffering from this complication present altered homeostasis of carnitine that
      results, by means of various mechanisms, in an alteration of the oxidative
      processes and damages the oxidative phosphorylation of the skeletal muscle. The
      effects of treatment with propionyl-l-carnitine (PLC) in a group of elderly
      patients with intermittent claudication (IC) are studied. METHODS: 39 elderly
      patients with IC were enrolled in an open study. The diagnosis was made using
      arterial colour ultrasonography of the lower limbs and patients were asked to
      perform the treadmill test. All patients received 300 mg i.v. PLC a day for 2
      weeks and 1 g twice a day per os for 18 weeks. Patients presenting heart,
      respiratory or other problems restricting physical exercise were excluded from
      the study. RESULTS: After 5 months of treatment an improvement was obtained in
      the distance after which IC appeared (from 213+/-8 m to 357+/-13 m) and the
      maximum distance covered (from 307+/-12 m to 549+/-23 m). CONCLUSIONS: The
      results of this study allowed us to evaluate the efficacy of this drug on the
      severely disabling pain affecting the quality of life of patients, thus enabling
      the maximum distance covered by these patients to be increased. Moreover, the
      drug was well tolerated (only two patients reported slight collateral effects
      ascribed to the drug) and safe to use. It represents a valid conservative, non
      surgical treatment which can be administered to all patients with intermittent
      claudication.

PMID- 11317142
TI  - Creatine as nutritional supplementation and medicinal product.
AB  - Because of assumed ergogenic effects, the creatine administration has become
      popular practice among subjects participating in different sports. Appropriate
      creatine monohydrate dosage may be considered a medicinal product since, in
      accordance with the Council Directive 65/65/EEC, any substance which may be
      administered with a view to restoring, correcting or modifying physiological
      functions in humans beings is considered a medicinal product. Thus, quality,
      efficacy and safety must characterise the substance. In addition, the European
      Court of Justice has held that a product which is recommended or described as
      having preventive or curative properties is a medicinal product even if it is
      generally considered as a foodstuff and even if it has no known therapeutic
      effect in the present state of scientific knowledge. In biochemical terms,
      creatine administration increases creatine and phosphocreatine muscle
      concentration, allowing for an accelerated rate of ATP synthesis. In
      thermodynamics terms, creatine stimulates the creatine-creatine kinase
      phosphocreatine circuit, which is related to the mitochondrial function as a
      highly organised system for the control of the subcellular adenylate pool. In
      pharmacokinetics terms, creatine entry into skeletal muscle is initially
      dependent on the extracellular concentration, but the creatine transport is
      subsequently downregulated. In pharmacodynamics terms, the creatine enhances the
      possibility to maintain power output during brief periods of high-intensity
      exercises. In spite of uncontrolled daily dosage and long-term administration, no
      researches on creatine monohydrate safety in humans were set up by standardised
      protocols of clinical pharmacology and toxicology, as currently occurs in phases
      I and II for products for human use. More or less documented side effects induced
      by creatine monohydrate are weight gain; influence on insulin production;
      feedback inhibition of endogenous creatine synthesis; long-term damages on renal
      function. A major point that related to the quality of creatine monohydrate
      products is the amount of creatine ingested in relation to the amount of
      contaminants present. During the industrial production of creatine monohydrate
      from sarcosine and cyanamide, variable amounts of contaminants (dicyandiamide,
      dihydrotriazines, creatinine, ions) are generated and, thus, their tolerable
      concentrations (ppm) must be defined and made consumers known. Furthermore,
      because sarcosine could originate from bovine tissues, the risk of contamination
      with prion of bovine spongiform encephalopathy (BSE or mad-cow disease) can t be
      excluded. Thus, French authorities forbade the sale of products containing
      creatine. Creatine, as other nutritional factors, can be used either at
      supplementary or therapeutic levels as a function of the dose. Supplementary
      doses of nutritional factors usually are of the order of the daily turnover,
      while therapeutic ones are three or more times higher. In a subject of 70 kg with
      a total creatine pool of 120 g, the daily turnover is approximately of 2 g. Thus,
      in healthy subjects nourished with fat-rich, carbohydrate, protein-poor diet and
      participating in a daily recreational sport, the oral creatine monohydrate
      supplementation should be of the order of the daily turnover, i.e., less than 2.5
      3 g per day, bringing the gastrointestinal absorption to account. In healthy
      athletes submitted daily to high-intensity strength or sprint training, the
      maximal oral creatine monohydrate supplementation should be of the order of two
      times the daily turnover, i.e., less than 5-6 g per day for less than two weeks,
      and the creatine monohydrate supplementation should be taken under appropriate
      medical supervision. The oral administration of more that 6 g per day of creatine
      monohydrate should be considered as a therapeutic intervention and should be
      prescribed by physicians only in the cases of suspected or proven deficiency, or
      in conditions of severe stress and/or injury. The incorporation of creatine into
      the medicinal product class is supported also by the use in pathological
      conditions, e.g., some mitochondrial cytopathies, the guanidinoacetate
      methyltransferase deficiency, etc.

PMID- 11317143
TI  - 18F-FDG PET mapping of regional brain activity in runners.
AB  - BACKGROUND: To examine regional metabolic changes in the human brain induced by
      free running in upright posture. METHODS. EXPERIMENTAL DESIGN: Regional brain
      changes in glucose uptake induced by running were examined by comparing brain
      images obtained by positron emission tomography (PET) and 18F-fluorodeoxyglucose
      (FDG). SETTING: The study was conducted at a research institute and involved
      participation of healthy young volunteers. Data sampling and analysis required
      special imaging device and special computer hardware/software. PARTICIPANTS:
      Subjects were 17 healthy male volunteers. They were divided at random into two
      equal groups, those who ran 4-5 km and the others sat in the room. MEASURES:
      differences in regional cerebral glucose uptake between runners and control
      groups were assessed statistically. Plasma glucose level was also measured and
      global cerebral uptake was estimated. RESULTS: Running was associated with a
      relative increase of glucose uptake in the temporoparietal association cortex,
      occipital cortex, premotor cortex and the cerebellar vermis. The highest activity
      was noted in the temporoparietal association cortex. Activity of the primary
      sensorimotor cortex was higher in the superomedial part (leg motor area) than the
      lateral part (thorax and arm). CONCLUSIONS: Running augmented energy consumption
      in the parieto-occipital region relative to the motor area, probably due to the
      higher energy consumption necessary for integration of multimodal sensory
      information than for generation of motor output. Our results indicate that FDG
      PET is a useful tool for brain mapping under various physiological conditions.

PMID- 11317144
TI  - Running economy and delayed onset muscle soreness.
AB  - BACKGROUND: The main purpose of this study was to test the effects of a duathlon
      competition on running economy. METHODS. EXPERIMENTAL DESIGN: A prospective
      study. SETTING: University. PARTICIPANTS: nine male and six female physical
      education students, which mean (SEM) age was 24.0 (1.3) years. MEASURES: Subjects
      participated in two competitive duathlons: D1 and D2 (5 km running + 16 km
      cycling + 2 km running). Before D1, an incremental exercise test on the treadmill
      was performed to determine the V O2max, the running speed at exhaustion (vmax),
      and the V O2, as well as the running speed (u) attained at the first and second
      ventilatory threshold (V O2V T1, uV T1, V O2V T2, uV T2). Two days later running
      economy (RE1) was assessed at four different speeds corresponding to 58, 63, 67
      and 71% of the umax. During the following six weeks the subjects trained 4 days a
      week, running all them 210 km in total. At the end of the training program the
      incremental exercise test and the duathlon competition were repeated (D2). Two
      and seven days after the second duathlon running economy was measured again (RE2
      and RE3, respectively). RESULTS: Small, but significant improvements were
      observed in duathlon performance, V O2max, umax, uV T1, V O2V T2 and uV T2, after
      training. Two days after D2 the oxygen cost of running was approximately 5%
      higher than seven days after D2 (p < 0.001). The respiratory exchange ratio
      increased by approximately 0.04 units between RE2 and RE3 (p < 0.001). However,
      the increase in fat oxidation in RE2 only accounted for approximately 20% of the
      extra oxygen cost of running (RE2 vs RE3). No significant differences across
      tests were observed for ventilation (V E), heart rate, V CO2 and V E/V CO2.
      CONCLUSIONS: This study shows that two days after a duathlon competition running
      economy is impaired, however, seven days after the competition the oxygen cost of
      running is restored.

PMID- 11317145
TI  - Contributions of strength and body composition to the gender difference in
      anaerobic power.
AB  - BACKGROUND: The purpose of this study was to determine the significant factors
      contributing to the difference between men and women in anaerobic power (AP)
      generation. METHODS. PARTICIPANTS: College men (n = 113) and women (n = 175) were
      randomly selected for evaluation from a fitness class prior to training.
      MEASURES: AP was determined from the Margaria-Kalamen stair run. Dynamic strength
      was evaluated from the 1-RM single-leg extension. Body composition was estimated
      from gender-specific skinfold prediction equations. RESULTS: Discriminant
      analysis identified %fat, fat-free mass (FFM), and leg extension strength as
      significant components differentiating between men and women and allowed proper
      gender classification in 99% of the cases. When both strength and body
      composition variables were held constant by covariance, there was no significant
      difference between men and women in AP (F = 1.25). A multiple regression equation
      using %fat, FFM, and leg extension strength predicted AP (R = 0.91) with an error
      of 150 W. When the multiple regression equations was applied to a cross
      validation sample, AP could be accurately predicted (r = 0.91, t = 0.17) with an
      average error of 3% +/- 21%. CONCLUSIONS: Body size and dynamic strength are the
      major factors explaining the explosive leg power difference between men and women
      without a specific or unique gender quality.

PMID- 11317146
TI  - Multiple-joint velocity-spectrum strength/power development consequent to
      repetition manipulation.
AB  - BACKGROUND: Various repetition strategies are employed in typical weight-training
      programs. Strength is purportedly best developed using relatively few repetitions
      against great resistance. Strength in this context has typically been measured
      isotonically (dynamic constant external resistance or DCER) by performing a one
      repetition maximum (1 RM). Multiple-joint isokinetic (velocity controlled)
      strength assessments are now available which may enable us to emulate movement
      patterns and velocities with those occurring in everyday activities while
      providing us with force and power information that heretofore has been difficult
      to obtain. Therefore, we assessed the effects of various repetition schemes
      during heavy-resistance training on multiple-joint isokinetic performance.
      METHODS. SETTING: Volunteers participated in 12 weeks (36 sessions) of variable
      resistance weight training (8 different exercises) in one of the following
      programs: I-3 sets x 3-4 RM; II-3 x 9-10 RM; III-3 x 15-16 RM; IV, control.
      PARTICIPANTS: 48 apparently-healthy young men (18 to 34 years of age, X = 23.2)
      who had not participated in systematic heavy-resistance training during the
      previous year. MEASURES: Pre and post velocity-spectrum tests were conducted for
      both the squat (0.41, 0.65, 0.90, 1.14, and 1.39 m x s(-1) and bench press (0.50,
      0.79, 1.09, 1.39 and 1.69 m x s-1) at which time peak force and peak power were
      measured. Force and power measurements were adjusted to control for body weight
      (N/kg and W/kg, respectively). Change (delta) scores were used for comparisons.
      RESULTS: One-way ANOVA s indicated that when compared to controls, improvements
      in force were significantly (p < 0.05) greater only at the slowest velocity
      (squats: Group II > Control; bench presses: Groups I, II, III > Control).
      However, changes in power were significantly (p < 0.05) greater than for controls
      at all 5 velocities tested (squats: Groups I, II > Control; bench presses: Groups
      I, II > Control except at 1.69 m x sec-1) where only Group I > Control).
      CONCLUSIONS: Due to the mixed findings for force improvements consequent to the
      various repetition schemes, conclusions are somewhat tentative. It appears,
      however, that strength increases only for slow velocities in young, previously
      untrained men consequent to 3 months of a relatively wide range of RM schemes
      using variable-resistance equipment. Power, on the other hand, appears to
      increase in the same subjects across a velocity spectrum for both squats and
      bench presses when no more than 10 RM are performed per set.

PMID- 11317147
TI  - Strength capabilities of knee extensor muscles in junior speed skaters.
AB  - BACKGROUND: The present study aimed to investigate the gender- and age-related
      profiles of junior speed skaters in strength capabilities during both single and
      repetitive maximal contractions. METHODS: The subjects were 19 male (age = 17.1
      +/- 0.2 years, X +/- SE) and 13 female skaters (16.9 +/- 0.2 years). Isokinetic
      knee extension torque (T) developed concentrically in a single contraction at
      three constant velocities of 1.05, 3.14 and 5.24 rad/sec and 50 repetitive
      maximal contractions at 3.14 rad/sec was measured using an isokinetic
      dynamometer. In addition, a B-mode ultrasound apparatus was used to determine the
      cross-sectional area (CSA) of the quadriceps femoris muscle at mid-thigh.
      RESULTS: For the junior skaters, T values at three velocities of 1.05, 3.14 and
      5.24 rad/sec and the mean value of isokinetic torque (MT) for every five
      consecutive trials in the first 25 maximal contractions were similar in both
      genders when they were expressed relative to the product of the cross-sectional
      area (CSA) of the quadriceps femoris muscle and lower limb length, T/CSAL and
      MT/CSAL, respectively. However, the males showed significantly higher MT/CSAL
      values than the females in the last 25 repetitions of the endurance test. In the
      comparisons between junior and reference senior skaters, T/CSAL for both genders
      and MT/CSAL for the females showed little age-related difference. For the males,
      however, MT/CSAL values in the first 15 repetitions of the endurance test were
      significantly lower in the junior skaters than in the senior ones. CONCLUSIONS:
      The present results indicate that the strength capabilities of junior speed
      skaters in a single maximal contraction will be similar in both genders when the
      difference in muscle size is normalized. However, the junior male skaters may be
      less fatiguable than the junior female ones in repetitive maximal contractions.
      Moreover, the comparison between junior and senior skaters suggests that, in
      postadolescence, males might be more trainable than females to improve torque
      output during short-term repetitive maximal contractions beyond that achieved
      during adolescence.

PMID- 11317148
TI  - Aerobic and anaerobic power characteristics of Saudi elite soccer players.
AB  - BACKGROUND: To assess the aerobic and anaerobic characteristics of Saudi elite
      soccer players, and to examine the interrelationship between measures of aerobic
      and anaerobic power in the elite soccer players. METHODS. PARTICIPANT: Twenty
      three outfield elite soccer players representing the Saudi national team
      participated. Their means (+/- SD) for age, body mass, height and estimated fat %
      were: 25.2 +/- 2.3 years; 73.1 +/- 6.8 kg; 177.2 +/- 5.9 cm; and 12.3 +/- 2.7%,
      respectively. MEASURES: Cardiorespiratory parameters, including maximal oxygen
      uptake (V O2 max), were assessed by open-circuit spirometry during graded
      treadmill running. Anaerobic power measures were obtained using Wingate anaerobic
      test, and included peak power (PP), and average power for 5 sec (AP 5), 10 sec
      (AP 10), 20 sec (AP 20) and 30 sec (AP 30). RESULTS: Mean (+/-SD) values for V
      O2max in absolute and relative to body mass were 4.16 +/- 0.34 l x min-1 and 56.8
      +/- 4.8 ml x kg-1 x min-1, respectively. Such V O2max value was 118% and 80% of
      those reported for Saudi college males and distance runners, respectively. The
      ventilatory anaerobic thereshold (Tvent) averaged 43.6 ml x kg-1 x min-1. There
      were no significant differences in V O2max and Tvent between players based on
      positions, although the midfielders and the centre-backs had the highest and the
      lowest individual values for both measures, respectively. Values (+/- SD) of PP
      and AP 30 were 873.6 +/- 141.8 W (11.88 +/- 1.3 W x kg-1), and 587.7 +/-55.4 W
      (8.02 +/- 0.53 W x kg-1), respectively. Only in absolute PP & AP 30 were the
      centre-backs significantly superior to the other players. In addition, V O2max
      was inversely related to PP (r = - 0.54; p < 0.05) and positively related to AP
      30 (r = 0.45; p < 0.05). CONCLUSIONS: The aerobic power, expressed relative to
      body mass, of Saudi elite soccer players was in the lower range of values
      normally reported in the literatures for elite soccer players. Both PP and AP 30
      were somewhat lower than values previously reported for elite soccer players from
      other countries.

PMID- 11317149
TI  - Relationship of measures of leisure time physical activity to physical fitness
      indicators in Spanish adults.
AB  - BACKGROUND: The purpose of our study was to examine the association between
      estimates of energy expenditure obtained by the Minnesota Leisure Time Physical
      Activity questionnarie (LTPA) and physical fitness indicators. METHODS.
      PARTICIPANTS: An adaptation of the LTPA was assessed in a sample of Spanish
      population: male (n = 44) and female (n = 38). INTERVENTIONS: the LTPA 1 year
      recall questionnaire was administered twice with a 12-month interval and
      participants also responded monthly the Four Week Physical Activity History (FWH)
      questionnaire. MEASURES: test-retest reliability of the LTPA and the
      relationships between changes in V.O2max, percent body fat and leisure time
      physical activity were examined. RESULTS: Corresponding components of the LTPA
      and the FHW were highly correlated and scores in heavy leisure time activities
      and household chores showed a relatively low variance ratio, indicating an
      acceptable reliability of the questionnaire. Heavy intensity physical activity
      and household chores were highly related to V.O2max and there was a weaker
      association to moderate or light activity. CONCLUSIONS: Our results suggest that
      the Spanish version of the LTPA is a relatively valid and reliable measure of
      regular physical activity and a valid estimator of cardiorespiratory fitness in
      adults.

PMID- 11317150
TI  - Grip strength measurement in competitive ten-pin bowlers.
AB  - BACKGROUND: In an attempt to find a more specific grip strength test for bowlers,
      the conventional grip strength test was modified such that only the fingers used
      in holding the ball are tested. The objective of this study was to assess the
      test-retest reliability of this modified bowling grip strength test, to assess
      the agreement between the bowling and the conventional grip strength tests, and
      to examine the correlation between the modified test and bowling performance in
      competitive bowlers. METHODS. EXPERIMENTAL DESIGN: This research was conducted in
      two parts, each with a different study sample. Study I was a cross-sectional
      study to assess the correlation between the bowling grip strength and the bowling
      score. Study II was a comparative study to obtain the test-retest reliability for
      both the bowling and conventional grip strength tests, and to assess the
      agreement between the two tests. SETTING AND SUBJECTS: for study I, the subjects
      were 39 members (26 males and 13 females) of the Singapore National Ten-Pin
      Bowling Training Squad. Bowling grip strength was measured within one month prior
      to the selection trials for the national squad, the results of which were used as
      a measure of bowling performance. For study II, the subjects were 21 members (12
      males and 9 females) of the Singapore National Ten-Pin Bowling Squad that was
      formed after the selection trials. INTERVENTIONS: none. MEASURES: Bowling grip
      strength, conventional grip strength, and bowling score. RESULTS: The test-retest
      reliability of the bowling grip strength measurement (r = 0.91, p < 0.01) was
      comparable to that of the conventional five-finger grip (r = 0.93, p < 0.01). The
      single measure intraclass correlation coefficient between the bowling and
      conventional grip strength tests was 0.77; the 95% confidence interval was 0.51
      and 0.90. However, the correlation coefficient between the bowling grip strength
      test and bowling score (r = 0.27) was not significant. CONCLUSIONS: The bowling
      grip strength test has a high test-retest reliability, and a moderate agreement
      with the conventional grip strength test. However, despite using only the bowling
      fingers, the test was unable to predict bowling performance in elite bowlers.

PMID- 11317151
TI  - Responses of blood hormones to the maximal rowing ergometer test in college
      rowers.
AB  - BACKGROUND: The purposes of this study were to investigate the resting levels and
      the acute hormonal response of total testosterone (Ttot), free testosterone
      (Tfree), cortisol (C) and Tfree:C ratio to the 6-minute all-out rowing ergometer
      test. METHODS. EXPERIMENTAL DESIGN: Cross-sectional study to investigate the
      responses of blood hormones to the maximal rowing ergometer test in college
      rowers. PARTICIPANTS: Eight college level male rowers (22.0 +/- 2.8 yrs, 191.8 +/
      4.1 cm, 85.4 +/- 4.3 kg, BMI: 23.2 +/- 1.3 kg x m(-2)) took part in this
      investigation. INTERVENTIONS: a graded exercise test at the intensities of 150,
      200 and 250 W (6-minute each) and a 6-minute all-out test on a rowing ergometer
      (Concept II, Morrisville, USA) were performed at separate measurement sessions.
      MEASURES: Heart rate (HR) was recorded at the end of each load during a graded
      exercise test. Individual physical working capacity of rowers was calculated at
      the maximum HR recorded during a 6-minute all-out test. Venous blood samples were
      obtained 3 minutes before and immediately after the 6-minute all-out test to
      determine the concentration of Ttot, Tfree, Tfree:C ratio, glucose and lactate
      (LA) in blood. RESULTS: Mean power was 354.3 +/- 26.8 W and HR 190.9 +/- 5.1
      beats x min(-1) during the all-out test. Mean blood LA concentration at the end
      of the all-out test was 13.4 +/- 1.44 mmol x l(-1). The all-out test on the
      rowing ergometer did not change significantly the concentration of Ttot (before:
      17.54+/-4.34; after: 20.03 +/- 4.80 nmol x l(-1)), Tfree (before: 0.423 +/-
      0.111; after: 0.436 +/- 0.112), C (before: 477.50 +/- 119.34; after: 477.63+/
      132.51 nmol x l(-1)) and Tfree:C ratio (before: 0.922 +/- 0.282; after: 0.973 +/-
      0.320 x10(-3)). The transformation of these hormone values to effect sizes (ES)
      demonstrated that all-out test only moderately (ES < 0.61) influenced these
      hormone levels. Significant relationships were observed between the resting
      levels of Ttot and Tfree, and mean power of the 6-minute all-out test (r = 0.65
      and r = 0.86, respectively). There was a non-significant increase in the level of
      Ttot following the all-out rowing ergometer test which was significantly related
      to mean power (r = 0.73) and covered distance (r = 0.67). CONCLUSIONS: The
      results suggest that there are no significant changes in hormone levels during a
      6-minute all-out rowing ergometer test. However, rowing performance is positively
      related to the resting values of Ttot and Tfree, and the non-significant changes
      in Ttot level following a 6-minute all-out test.

PMID- 11317152
TI  - Lack of correlation between 6-month fluctuations in habitual physical activity
      and testosterone. Concentrations in elderly subjects.
AB  - BACKGROUND: To examine the influence of long-term modifications in habitual
      physical activity (PA) on resting total testosterone (TT) concentrations in a
      group of healthy elderly subjects. METHODS:  EXPERIMENTAL DESIGN: 6-month
      prospective study. SETTING: University research departments of exercise
      physiology and geriatric medicine. PARTICIPANTS: thirty-one independent,
      community dwelling elderly subjects (16 men and 15 women) aged > 65 who
      volunteered to participate. INTERVENTIONS: correlational study. MEASURES: PA was
      evaluated by a questionnaire QAPSE (Questionnaire d Activite Physique Saint
      Etienne) and expressed by two activity indices: mean habitual daily energy
      expenditure (MHDEE) and daily energy expenditure corresponding to leisure time
      sports activities (Sports activity index). RESULTS: Changes in resting TT
      concentrations were not related to changes in MHDEE (r = -0.28; p = 0.30 and r = 
      0.001; p=0.99) and Sports activity (r = -0.30; p = 0.26 and r = -0.05; p = 0.85)
      in men and women, respectively. Similarly, relative (%) changes in TT were not
      related to relative changes in MHDEE (r = -0.16; p=0.55 and r = 0.17; p=0.55) and
      Sports activity (r = -0.11; p=0.68 and r = 0.02; p = 0.92). CONCLUSIONS: The
      levels of habitual PA undertaken by an average senior do not appear to affect TT
      levels in healthy active elderly men and women.

PMID- 11317153
TI  - Effect of oral contraceptives on peripheral blood flow in untrained women at rest
      and during exercise.
AB  - BACKGROUND: Endothelium-derived nitric oxide is an important mediator of exercise
      induced changes in skeletal muscle blood flow. Given the recently documented
      effects of estrogens on nitric oxide synthase, it is hypothesized that oral
      contraceptives (OC) containing estrogen would increase nitric oxide production at
      rest and after endurance exercise. Further, we postulated that OC use would
      augment skeletal muscle blood flow at rest and during exercise. METHODS: Fourteen
      women (non-smokers) were divided into two groups: control (CON; sedentary, normal
      menstrual-cycling women who have not used oral contraceptives for > or = 12 mons;
      18-38 yrs old; n = 7), and oral contraceptive users (OC; sedentary women who have
      been using low-dose estrogen/progestin oral contraceptives for > or = 12 mons; 19
      38 yrs old; n = 7). Measurements of forearm blood flow were obtained from each
      group, using strain gauge plethysmography, at rest and during an exercise
      protocol in which intermittent handgrip exercise was performed at 15%, 30%, and
      45% of maximum voluntary contraction (MVC). Additionally, venous blood samples
      were taken before and after a 90 min treadmill walk for measurement of serum
      nitrate/nitrite, an indirect assessment of steady-state nitric oxide production.
      RESULTS: There was no difference in forearm blood flow (ml/min/ 100 cc tissue) at
      rest (CON = 2.7; OC = 2.8); however, the hyperemic response to handgrip exercise
      was significantly (p < 0.05) lower in the OC group at 30% (9.0 vs CON = 14.2) and
      45% (12.0 vs CON=17.0) of MVC. Serum nitrate values at rest and following 90 min
      of treadmill walking did not differ between groups (p > 0.05). CONCLUSIONS:
      Contrary to our hypotheses, these data indicate a compromised hyperemic response
      in the forearm of OC users. Further, chronic OC use may not affect nitric oxide
      production during low intensity treadmill exercise.

PMID- 11317154
TI  - Hormonal and metabolic response in elite female gymnasts undergoing strenuous
      training and supplementation with SUPRO Brand Isolated Soy Protein.
AB  - BACKGROUND: This study evaluates the metabolic and hormonal response in elite
      female gymnasts undergoing strenuous training and supplementation with SUPRO
      Brand Isolated Soy Protein. METHODS. EXPERIMENTAL DESIGN: 14 top female gymnasts
      (Romanian Olympic Team), took part in a study to examine their hormonal metabolic
      profile and to investigate any possible changes resulting from a 4-month program
      of strenuous training and daily supplementation with soy protein at a level of 1
      g/kg body weight. Gymnasts wtare randomly assigned to one of two groups seven to
      the Supplemented Group (A) and seven to the Non-Supplemented Group (B). Both
      groups took part in the same program, which consisted of strenuous training for 4
      6 hours/day (except on Sunday, controlled food intake and supplements including
      vitamins and minerals. Group A received a supplement of Sports Beverage Protein
      Mix with SUPRO Isolated Soy Protein (ISP) twice daily. Group B received a placebo
      identical in appearance and flavour. Selected parameters were measured before and
      after the 4-month training program (lean body mass, fat mass, serum hemoglobin,
      protein, fats, urea and creatinine, liver enzymes, serum total calcium and
      magnesium, immunoglobulins, urinary mucoproteins, serum T3 and T4, estradiol,
      progesterone, prolactin, testosterone and urinary 17-ketosteroids). RESULTS:
      Results demonstrated that the Supplemented Group (A) had an increase in lean body
      mass and serum levels of prolactin (p < 0.01) and T4 and a decrease in serum
      alkaline phosphetases (p < 0.01). The Non-Supplemented Group (B) had a decreased
      level of serum T4 and an increased level of urinary mucoproteins (p < 0.05).
      CONCLUSIONS: Our preliminary conclusions might suggest lower metabolic-hormonal
      stress in elite female gymnasts undergoing strenuous training and who received
      daily supplementation with isolated soy protein.

PMID- 11317155
TI  - Postexercise proteinuria in humans and its adrenergic component.
AB  - BACKGROUND: Postexercise proteinuria is a common phenomenon depending on
      hypothetical mechanisms such as the hemodynamic system and its sympathetic
      component. To test this hypothesis we administrated an a2-adrenergic agonist
      (clonidine) in order to reduce the catecholamine response during exercise.
      METHODS: Clonidine (300 mg) and a placebo, one week apart, were administrated
      randomly to nine healthy male subjects (23 yrs age) 2 hours prior to a maximal
      exercise test on bicycle ergometer. Blood samples and urine collections were
      obtained at rest and after exercise. Lactate in plasma, creatinine and albumin in
      plasma and urine were assayed and their clearances were calculated. RESULTS:
      Postexercise lactate was identical under placebo and clonidine administration
      (10.1 +/- 1.0 versus 11.3 +/- 1.7 mmol.-1). It was observed that the clonidine
      treatment induced a lesser postexercise proteinuria (213 +/- 28 versus 298 +/- 55
      mg.min-1) and albuminuria (71.8 +/- 16.3 versus 116.8 +/- 34.2 mg.min-1) when
      compared to the placebo test. The postexercise renal clearance of albumin did
      show a reduction of 40% under the influence of clonidine. CONCLUSIONS: It may be
      argued that the catecholamines are partially acting on the mechanisms of the
      enhanced permeability of the glomerular membrane induced by strenuous exercise.

PMID- 11317156
TI  - Effects of aerobic exercise training on 24 hr profile of heart rate variability
      in female athletes.
AB  - BACKGROUND: The aim of this study was to investigate the effects of exercise
      training on autonomic regulation of heart rate under daily life conditions.
      METHODS: Twenty-six healthy female athletes (age 24.5 +/- 1.9 yrs) involved in
      regular physical activity were recruited during a period of yearly rest and
      randomly assigned to a five-week aerobic exercise training program (n = 13) or to
      a non-exercise control group (n = 13). MEASURES: Before and after the five-week
      training, all subjects underwent a bycicle ergometer stress test and a 24-hour
      dynamic ECG monitoring. Autonomic regulation of heart rate has been investigated
      by means of both time and frequency domain analyses of heart rate variability
      (HRV). Spectral analysis of R-R interval variability (autoregressive algorithm)
      provided markers of sympathetic (low frequency, LF, 0.10 Hz) and parasympathetic
      (high frequency, HF, 0.25 Hz) modulation of the sinus node. RESULTS: Trained
      subjects showed a reduced heart rate response to submaximal workload. Before
      training there was no significant difference between the two groups. After
      training resting heart rate did not significantly differ between trained and
      untrained subjects. No significant differences were observed in the different
      time domain indexes of heart rate variability. The day-night difference in SD and
      SDRR were significantly less in the trained as compared to the untrained group.
      Normalized LF and HF components did not significantly differ between trained and
      untrained subjects, during the awake period. The decrease in the LF and the
      increase in the HF component during nighttime were significantly less in the
      trained group. The LF/HF ratio was significantly decreased during the night in
      the untrained group whereas it was not significantly different from the awake
      state in the trained group. CONCLUSIONS: These findings of the relative night
      time increase in LF and the decrease in the day-night difference in time domain
      indexes of heart rate variability suggest that, in young female athletes,
      exercise training is able to induce an increase in the sympathetic modulation of
      the sinus node which may coexist with signs of relatively reduced, or unaffected,
      vagal modulation.

PMID- 11317157
TI  - The Tei index and exercise capacity.
AB  - BACKGROUND: Cardiac function time intervals are known to change with aerobic
      fitness. Recently, the Tei index of cardiac function [defined as the sum of the
      isovolumetric contraction (ICI) and isovolumetric relaxation intervals (IRI)
      divided by the left ventricular ejection time (LVET)] has been proposed to be a
      very sensitive determinant of cardiac function in patients with cardiomyopathy,
      i.e. the index is greater in patients with cardiomyopathy than it is in normal
      subjects. The purpose of this study was to determine the relationship between the
      Tei index and aerobic endurance in healthy volunteers. METHODS: The relatively
      new noninvasive method of seismocardiography was used to measure following
      resting left ventricular (LV) cardiac function time intervals in 51 subjects (18
      males and 33 females); Tei index, R-R interval, LV ICI, LV IRI, LVET, LV systole
      and LV diastole. Designated on the basis of peak treadmill time (Bruce protocol),
      the following three groups were assigned: Group 1; treadmill time > or = 900
      seconds; Group 2: treadmill time ranging from 721 to 899 seconds; and Group 3;
      treadmill time < 720 seconds. RESULTS: The Tei index value was lower as exercise
      capacity increased (p < 0.05) primarily due to a reduction in LV IRI (p < 0.05).
      LVET tended to be longer with increased treadmill time (p < 0.05) but this effect
      appeared to be secondary to a greater R-R interval in more fit subjects. When
      adjusted for the R-R interval, a reduced Tei index and LV IRI were still observed
      in more fit subjects, despite a similar LVET between groups. CONCLUSIONS: Peak
      treadmill time is inversely related to the Tei index. A reduction of LV IRI
      appears to be the primary factor in establishing these differences. These data
      support the important role of LV diastolic function in aerobic fitness.

PMID- 11317158
TI  - New prediction equation for residual volume in Japanese male and female young
      adults.
AB  - BACKGROUND: The purpose of this study was to establish a convenient prediction
      equation for residual volume for Japanese male and female young adults after
      comparisons in reliability and validity with previous equations widely used in
      studies of body composition with Japanese subjects. METHODS: The subjects were
      healthy Japanese, 110 males aged 18 to 27 years and 82 females aged 18 to 22
      years. Measured residual volume (MRV) was measured with a nitrogen washout
      technique and each predicted residual volume (PRV) was predicted using a
      prediction equation. Multiple regression analysis on all possible selections was
      applied to determine a suitable and convenient prediction equation for residual
      volume. RESULTS: Intra-class correlation coefficient and a coefficient of
      Cronbach in MRV exceeded 0.9, indicating high reliability. Pearson s correlation
      coefficients between MRV and each PRV for males and females ranged from 0.225 to
      0.327 and - 0.485 to 0.507, respectively. Multiple correlation coefficient
      adjusted for degrees of freedom applying the one variables of height was 0.592
      for males and 0.670 for females. CONCLUSIONS: Considering the practicability of
      measurement, prediction equations for residual volume with height in Japanese
      male and female young adults have been proposed. The new prediction equations
      (PRVnew) are as follows: male: PRVnew= 32.16 yen height (cm) - 4113.70 (Radj=
      0.592, SE= 247.13 ml); female: PRVnew = 34.03 yen height (cm) - 4407.78 (Radj=
      0.670, SE= 195.74 ml).

PMID- 11317159
TI  - Colonic fermentation after ingestion of fructose-containing sports drink.
AB  - BACKGROUND: Many commercially available sports drinks contain 5-6% carbohydrates,
      some of which is fructose. However, a number of studies of abdominal complaints
      have indicated fructose malabsorption. In the present study, we examined colonic
      fermentation of a fructose-containing sports drink. METHODS: Colonic fermentation
      was determined in normal subjects by measuring breath hydrogen after ingestion of
      350 ml sports drink, cow s milk, or green tea with a 200 g rice ball. RESULTS:
      The incidence of colonic fermentation after ingesting sports drink, milk, and
      green tea was five (62.5%), six (75%), and none (0%), respectively in eight
      subjects. Peak increases (ppm) after ingestion of sports drink and milk varied
      from 0 to 6 (3.1 +/- 0.9) and 0 to 12 (6.5 +/- 1.7), respectively. CONCLUSIONS:
      Although the increase of breath hydrogen was not associated with abdominal
      discomfort and its effect on exercise is still unclear, we suggest avoiding a
      large ingestion of fructose-containing sports drink before and during exercise.

PMID- 11317160
TI  - Scale construction for measuring attitude, beliefs, perception of control, and
      intention to exercise.
AB  - BACKGROUND: Using the Theory of Planned Behavior as a framework, the Fitness
      Attitude, Expectations of Others, Perceived Behavioral Control, and Intention to
      Exercise Scales were developed. Professionals in exercise physiology generated
      items for the instruments. Experts in clinical psychology and exercise physiology
      established content validity. METHODS: Each of the scale items is phrased in a
      rating scale format. Both unipolar and bipolar scales were developed with seven
      response choices offered. Following the pilot testing and subsequent revisions,
      19 items were retained in the Fitness Attitude Scale, seven items were retained
      in the Expectations of Others Scale, three items were retained in the Perceived
      Behavioral Control Scale, and 11 items were retained in the Intention to Exercise
      Scale. RESULTS: Correlation coefficients for the total instruments were
      significantly positive for stability and internal consistency, ranging from a =
      0.75 to a = 0.87. Exercise specialists may wish to implement the use of these
      scales in their practices to develop intervention techniques for the promotion of
      positive fitness attitudes, good perception of control over the ability to
      exercise, and good intentions to exercise. CONCLUSIONS: The positive results in
      this study s sample suggest that these scales are ready for application in the
      field, but they should be pilot-tested with each group to check reliability with
      the particular population.

PMID- 11317161
TI  - Attitudes of coaches towards doping.
AB  - BACKGROUND: Coaches are usually held to be among the main actors of doping
      prevention campaigns. The aim of this study was to document certain attitudes of
      professional coaches faced with doping, and to evaluate how they confronted it on
      an everyday basis. METHODS:  EXPERIMENTAL DESIGN: prospective study by self
      reporting questionnaire. SETTING AND PARTICIPANTS: the questionnaire was mailed
      to the last 800 graduated coaches (1994-1997) in the Lorraine region, Eastern
      France. The 260 responding coaches comprised 77 women and 183 men, the average
      age being 30.8 +/- 8.0 years (mean +/- standard deviation). RESULTS: 10.3% of
      coaches consider that an athlete may use doping with no health hazard with the
      help of a physician, and 30.0% that an athlete who declines doping has little
      chance of succeeding. 5.8% had used doping drugs in the last twelve months (1 to
      6 times). 13.5% of coaches mention that athletes (1 to 5 per coach on average)
      told them they had been prompted to use doping drugs during the previous 12
      months. 80.7% consider that the current methods of preventing doping in sport are
      ineffective, and 98.1% of them consider that they have a role to play within this
      context, but 80.3% consider themselves badly trained in the prevention of doping.
      Only 10.4% have organized a doping prevention action during the last 12 months.
      CONCLUSIONS: In this study, professional coaches do not seem to be efficient in
      the prevention of doping. Further education and training for coaches on doping is
      advisable.

PMID- 11317162
TI  - Is the evidence right in evidence-based practice?

PMID- 11317163
TI  - COX-1 sparing and COX-2 inhibitory drugs: the renal and hepatic safety and
      tolerability profiles of celecoxib.

PMID- 11317164
TI  - The hepatic safety and tolerability of the novel cyclooxygenase-2 inhibitor
      celecoxib.
AB  - Celecoxib is a cyclooxygenase- (COX)-1-sparing inhibitor of COX-2 that is
      indicated for the treatment of osteoarthritis and rheumatoid arthritis. Many
      agents used for treating these diseases, both symptom-modifying and disease
      modifying, are associated with the potential for hepatotoxicity. This article
      presents an analysis of the hepatic effects of celecoxib in 14 controlled studies
      of patients with arthritis (2 to 24 weeks' duration), in a long-term, open-label
      safety study (as long as 2 years), in 11 studies of patients receiving treatment
      for pain after oral or orthopedic surgery (up to 5 days' duration), and in five
      pharmacology studies. The overall incidence of hepatic adverse events in
      arthritis patients receiving celecoxib was similar to that for placebo but
      significantly lower than in the combined group of patients receiving nonsteroidal
      anti-inflammatory drugs (NSAIDs). The most commonly reported hepatic adverse
      events were elevations in liver transaminase levels, most of which occurred in
      patients receiving diclofenac. Similarly, clinically significant elevations of
      transaminase levels occurred more frequently with NSAIDs than with celecoxib. A
      pharmacology study performed in patients with mild or moderate hepatic impairment
      showed that celecoxib did not produce any clinically relevant changes from
      baseline in creatinine clearance, alanine aminotransferase, or bilirubin values
      in these settings. In the four interaction studies performed with drugs
      metabolized in the liver, none of the adverse events was hepatic in nature, and
      no clinically relevant liver function test abnormalities occurred. In conclusion,
      this analysis suggests that celecoxib has a very low potential for hepatic
      toxicity, even after exposures of as long as 2 years at therapeutic doses.

PMID- 11317165
TI  - Renal safety and tolerability of celecoxib, a novel cyclooxygenase-2 inhibitor.
AB  - The novel cyclooxygenase- (COX)-2 inhibitor celecoxib is an effective treatment
      for the signs and symptoms of osteoarthritis and rheumatoid arthritis.
      Conventional treatment for these debilitating conditions routinely involves the
      use of conventional nonsteroidal anti-inflammatory drugs (NSAIDs), which are
      nonspecific inhibitors of COX-1 and COX-2. Numerous studies suggest that
      inhibition of renal prostaglandin synthesis by NSAIDs is deleterious to kidney
      function, particularly in high-risk patients. As celecoxib inhibits COX-2 and
      spares COX-1 at therapeutic doses, we hypothesized that it may offer an improved
      renal safety profile in patients at risk for NSAID-induced renal toxicity. This
      article represents a post hoc analysis of the renal safety of celecoxib, using
      the safety database generated during its clinical development program. This
      analysis includes data from more than 50 clinical studies involving more than
      13,000 subjects. Most subjects were enrolled in randomized, controlled trials (of
      up to 12 weeks' duration); however, more than 5000 subjects received celecoxib
      for as long as 2 years in a long-term, open-label study at as much as twice the
      maximum recommended dosage. The overall incidence of renal adverse events after
      celecoxib was greater than that after placebo but similar to that after NSAIDs.
      The most common events reported after celecoxib, namely, peripheral edema (2.1%),
      hypertension (0.8%), and exacerbation of preexisting hypertension (0.6%), were
      not time- or dose-related. Peripheral edema was not associated with increased
      weight or blood pressure. Furthermore, there was no evidence of drug-drug
      interactions between celecoxib and concomitant angiotensin-converting enzyme
      (ACE) inhibitors, beta-blockers, calcium channel blockers, or diuretics. We
      conclude that celecoxib is well tolerated by patients who may be at risk for
      NSAID-induced renal toxicity, such as the elderly and those with hypertension or
      preexisting chronic heart disease.

PMID- 11317166
TI  - Ambulatory blood pressure profiles in patients treated with once-daily diltiazem
      extended-release or indapamide alone or in combination.
AB  - This randomized, double-blind, placebo-controlled, parallel-group study evaluated
      the efficacy and safety of single daily dose diltiazem extended-release (XR) and
      indapamide, given alone and combined, in 255 male and 170 female patients with
      mild to moderate hypertension. Blood pressure was assessed both manually in the
      office and by 24-hour ambulatory blood pressure monitoring (ABPM) techniques.
      Between-treatment efficacy comparisons were based on ABPM plots and changes from
      baseline in supine systolic (SuSBP) and diastolic (SuDBP) blood pressure after 6
      weeks of double-blind treatment. Periodic 12-lead electrocardiograms (ECG),
      clinical laboratory tests, and physical examinations were used to assess safety.
      Both diltiazem XR 180, 240, and 360 mg and indapamide 2.5 mg monotherapy reduced
      ambulatory blood pressure to a greater extent than placebo. The ABPM data
      demonstrate that 2.5 mg indapamide produces an additional reduction in diastolic
      blood pressure when combined with fixed doses of diltiazem XR (120, 180, and 240
      mg). The reduction was consistent over the entire 24-hour recording period for
      all combinations. Compared with monotherapy groups, higher therapeutic response
      rates (SuDBP < or = 90 mm Hg or Delta SuDBP > or = 10 mm Hg decrease from
      baseline) were also observed with combination therapy. Office blood pressure data
      qualitatively and quantitatively supported the observations made from the ABPM
      data. There were no unexpected adverse events or side-effect trends and no dose
      response or clinically significant laboratory, ECG, or physical examination
      adverse effects. The combination therapy regimens were well tolerated with safety
      profiles comparable with those of the individual therapies.

PMID- 11317167
TI  - Degradation kinetics of leucine5-enkephalin by plasma samples from healthy
      controls and various patient populations: in vitro drug effects.
AB  - Incubation of [3H]tyrosine leucine5-enkephalin with platelet-poor human plasma
      (final concentration 1 x 10(-8) M; 1:9 ratio to Trizma base buffer, pH 7.4)
      resulted in rapid and complete peptide degradation in each of the subjects
      studied, with more than 95% of the initial labeled tyrosine consistently
      recovered as the free amino acid (< or =30 minutes). Essentially, and
      irrespective of the incubation time (1-180 minutes), tyrosine was the only Leu
      metabolite formed; we were unable to identify significant amounts (> or =3%) of
      any other possible labeled or nonlabeled Leu degradation fragments. Neither
      gender (64 men and 20 women; samples tested individually), age (men, 23-70;
      women, 25-65 years), nor the subjects' medical condition appeared to make a
      significant difference in either the t1/2 of Leu elimination, the initial
      velocity of this reaction (x +/- SD, median, minimum and maximum of 12.0 +/- 0.9,
      12.0, and 10.6-13.7 minutes; 1.2 +/- 0.3, 1.1, and 0.6-2.0 pg/min, respectively),
      or in the Km and Vmax values for aminopeptidase Leu degradation (x +/- SD; 0.81
      +/- 0.01 mM and 14.30 +/- 1.17 micromol/L/min, respectively). Subjects were
      diagnosed as chronic schizophrenics (n = 15), polydrug abusers including alcohol
      (n = 9) and polydrug abusers excluding alcohol (n = 8), chronic alcoholics (n =
      12), and migraineurs (n = 10) during or outside an acute migraine episode; for
      comparison we used a group of gender-matched (20 men and 10 women), age
      comparable, drug-free, healthy volunteers. Differences in plasma storage time or
      repeated sample freezing and thawing failed to alter significantly any of these
      kinetic parameters of Leu metabolism or to change the identity and/or relative
      ratio of the products formed. The Leu degradation rate was pH and temperature
      dependent (optimum, 7.4 and 37 degrees C, respectively). Leu degradation was
      strongly and similarly inhibited by puromycin, bacitracin, and bestatin (IC50 [+/
      SD] of 1.4 +/- 0.2 micromol/L) and to a lesser extent by various L-tyrosine
      containing Leu fragments. The kinetics of this reaction was not significantly
      affected by either thiorphan, N-carboxyphenylmethyl leucine, or any other of a
      number of monoamine neurotransmitters, substances of abuse, nonsteroidal anti
      inflammatory agents, and miscellaneous compounds tested (concentration up to 10(
      4) mol/L).

PMID- 11317169
TI  - Recognition and management of depression in primary care: a focus on the elderly.
      A pharmacotherapeutic overview of the selection process among the traditional and
      new antidepressants.
AB  - Depressed patients consult with their primary care physician before engaging the
      services of a mental health care provider. Primary care physicians initiate more
      antidepressant pharmacotherapy than psychiatrists. Major depression has been
      estimated to have a 5% to 10% prevalence, with up to three times that percentage
      having significant subsyndromal depression symptoms. Patients frequently deny
      their depression, often neglecting to recognize their own somatic and
      cognitive/behavioral subjective symptoms, underestimating symptom severity, and
      possessing a reluctance to validate their existence because of social stigmata.
      There remains an underrecognition of the diagnosis of depression by primary care
      physicians. Often, depressed primary care patients present with somatic symptoms,
      which include gastrointestinal, skeletal muscle, and cardiovascular complaints,
      as opposed to describing nonsomatic criteria for depression. Elderly patients
      presenting with depression have an estimated prevalence of 5% to 50%, and the
      rate of suicide increases with age. In this patient group, depression may exist
      independently or secondary to insults or events. Major depressive disorders occur
      throughout the life cycle; however, the rate of major depression has increased,
      and the age of onset has become younger. Not uncommonly, complicating
      psychosocial factors coupled with multiple chronic disease states and physical
      pathology may mask the diagnosis of depression. Furthermore, up to 25% of
      extended care facility patients may satisfy the Diagnostic and Statistical Manual
      of Mental Disorders, fourth edition (DSM-IV) criteria for depression. Comorbid
      diseases and pharmacotherapy have been associated with secondary depression.
      Antidepressant pharmacotherapy combined with cognitive and behavioral therapy
      appears to offer the most benefit to the patient. Antidepressants independently
      act as catalysts to facilitate or correct the dysregulation of neurotransmission
      in depressed patients. The elderly present pharmacotherapeutic challenges based
      on a changing internal milieu in the absorption, distribution, metabolism, and
      elimination of most of the antidepressants. Polypharmacy may act to induce or
      inhibit the metabolism of substrate medication that the patient is currently
      using. A comprehensive list of cytochrome P450 interactions is provided.
      Generally the antidepressants display similarity in efficacy; however,
      effectiveness may be substantially different among and within antidepressant
      pharmacotherapeutic classes. The pharmacotherapeutic selection of antidepressants
      is a multifactorial cognitive process, including consideration of medication side
      effects and adverse effects and patient-specific factors. Other factors in this
      selection process include drug interaction potential, patient's prior drug
      response, and both the patient's concomitant pathology and pathophysiology and
      pharmacotherapy-mediated events. In conjunction with age-related, gender-related,
      and genetic factors, a full description of current serotonin pharmacotherapy
      mediated events is provided. Included in this article are a review of traditional
      and newer antidepressants, their pharmacokinetics, their pharmacodynamics, and an
      elaborate interaction focus. Special emphasis is focused on individual
      antidepressants and class of antidepressants. This article provides comprehensive
      insights in perception, recognition, treatment, and the selection process
      involving antidepressants.

PMID- 11317168
TI  - Immunomodulatory and clinical effects of Viscum album (Iscador M and Iscador P)
      in children with recurrent respiratory infections as a result of the Chernobyl
      nuclear accident.
AB  - Ninety-two children 5 to 14 years of age living in areas exposed to the
      radioactive fallout from Chernobyl with recurrent respiratory infections (RRIs)
      were treated after randomization with either Viscum album praeparatum mali or
      pini (Iscador M or P). The dosage was two subcutaneous injections a week for 5
      weeks with individual doses of 0.001 mg to 1.0 mg. Both Viscum album preparations
      were effective in significantly reducing clinical symptoms. One year after a
      single treatment course, the frequency of RRI relapses decreased by 78% and 73%,
      respectively. Immunomodulatory effects were assessed by investigation of
      lymphocyte subsets, natural killer (NK) cell activity, phagocytic and oxidative
      activity of polymorphonuclear leukocytes, and antiviral activity of serum before
      and 1 week after treatment. Viscum album therapy resulted in normalization of
      initial immune indices either below or above the normal ranges. High levels of
      antiviral activity before treatment were significantly decreased by Viscum album
      mali. Viscum album treatment should be studied further in children with RRI.

PMID- 11317170
TI  - A choice, not an echo.

PMID- 11317171
TI  - Is clinical research oversight adequate in the United States?

PMID- 11317172
TI  - No gender effect on binding characteristics of phenytoin to serum proteins in
      monotherapy for adult patients with epilepsy.
AB  - The aim of the present study was to determine the gender-related binding
      characteristics of phenytoin (PHT) to serum proteins in adult patients with
      epilepsy. Serum samples examined in the study were obtained from 80 adult
      patients (40 men and 40 women) with epilepsy on PHT monotherapy. Their age ranged
      from 16 to 64 years (mean [SD], 36.0 [11.7] years). Protein binding of PHT was
      evaluated by ultrafiltration under current laboratory routine conditions (25 +/-
      3 degrees C). The in vivo binding parameters of PHT to serum proteins were
      determined using a binding equation derived from the Scatchard equation for a one
      site binding model. No significant differences were observed in age and serum
      concentrations of albumin between male and female patients (p > 0.05), but
      significant differences were observed in serum concentrations of total and
      unbound PHT between the two groups (p < 0.05). The mean association constant of
      PHT to serum proteins is the same value of 0.008 L micromol(-1) between male and
      female patients, whereas total concentration of binding sites seems to be similar
      between the two groups (1389 micromol L(-1) for men and 1345 micromol L(-1) for
      women). No significant differences were observed in binding characteristics of
      PHT to serum proteins between male and female patients (p > 0.05). Our results
      show that gender does not have a significant effect on the binding
      characteristics of PHT to serum proteins in adult patients receiving monotherapy
      under normal pathophysiologic conditions.

PMID- 11317173
TI  - Clarithromycin-induced alterations in vaginal flora.
AB  - Many antibiotics have been shown to alter both the bacterial and the fungal flora
      of the vagina, in some cases potentially increasing a woman's propensity toward
      urinary tract infections and vaginal candidiasis. The effects of some of the
      newer macrolide antibiotics on women's vaginal flora have not been previously
      studied, and almost none of the previous studies specifically cultured for
      effects on vaginal lactobacillus. Young women (ages 18-45 years) who were about
      to go onto therapy with clarithromycin, who did not have any conditions known to
      affect the vaginal flora (eg, diabetes mellitus, spermicide use, menopausal
      status without hormone replacement therapy), and who agreed to participate in the
      study were cultured with aerobic and anaerobic and fungal vaginal cultures before
      starting the antibiotic. These same women were then retested about 4 to 6 weeks
      after the start of their antibiotic course, and the results of their
      preantibiotic and postantibiotic cultures were compared. Lactobacillus was
      present in 33% of patients by vaginal culture before treatment, but this
      decreased to 0% after treatment. Escherichia coli was present in only 8% of
      patients before treatment, but this increased to 17% of patients after treatment.
      Enterococcus was present in 25% of patients before treatment but in only 8% of
      patients after treatment. The incidence of Gardnerella vaginalis was not affected
      by the treatment. Candida species incidence increased from 17% to 33% with
      treatment. The overall effects of clarithromycin on the vaginal flora are similar
      to other older antibiotics that have been tested.

PMID- 11317174
TI  - Practical considerations regarding the influence of the menstrual cycle on
      leukocyte parameters in clinical trials.
AB  - Variations in hormone levels during different phases of the menstrual cycle have
      been shown to alter the pharmacokinetics of some medications and are known to
      exert significant effects on seemingly unrelated physiologic parameters. Numerous
      studies have been undertaken to examine the effects of different phases of the
      menstrual cycle on leukocyte and differential counts, but results have often been
      inconclusive and contradictory. This study endeavored to reexamine these
      parameters, measured by standard laboratory assays, in healthy ovulating females
      to determine whether the menstrual cycle may have clinically relevant effects on
      leukocyte counts. Twenty-one women, aged 18 to 35 years and not taking hormonal
      contraception, were enrolled in an outpatient study within 12 hours after the
      onset of normal menses. The women reported to the clinical pharmacology unit for
      a complete blood count with differential on days 1, 2, 7, 10 through 17, 22, and
      25 through 32. Blinded duplicate samples were obtained on day 2 to assess
      variability at the analytic site, and levels of luteinizing hormone and estradiol
      were measured on days 11 through 16 to determine the day of ovulation. Eighteen
      women completed the study, with cycle lengths ranging from 24 to 31 days (28.2 +/
      1.9 days, mean +/- SD). Evaluations of the data revealed a trend toward higher
      leukocyte counts and absolute neutrophil counts at the onset of menses but no
      significant or clinically relevant effects of different phases of the menstrual
      cycle on these parameters. Some split samples showed considerable variation in
      the assays (eg, a 42% increase in absolute neutrophil counts), suggesting that
      errors at the analytic facility may be a more important consideration than
      hormonal effects.

PMID- 11317175
TI  - Pharmacokinetic interactions among phenobarbital, carbamazepine, and valproic
      acid in pediatric Japanese patients: clinical considerations on steady-state
      serum concentration-dose ratios.
AB  - With antiepileptic drugs, the marked inter- and intrapatient variability of the
      concentration-dose ratio makes it difficult to predict serum concentrations from
      the dose administered per kilogram. The effects of comedication on steady-state
      serum concentration/dose ratios of antiepileptic drugs were evaluated
      retrospectively in 669 pediatric patients. To avoid complex pharmacokinetic
      interactions among multiple antiepileptic drugs, the data on serum concentrations
      in the current study were collected from patients who were co-administered only
      one additional antiepileptic drug (phenobarbital-carbamazepine, phenobarbital
      valproic acid, or carbamazepine-valproic acid) or who received monotherapy. The
      concentration/dose ratio for the antiepileptic drugs increased significantly with
      body weight in children up to 15 years old. Associated therapy with antiepileptic
      drugs affected the concentration/dose ratio. Therefore, routine monitoring of
      serum concentrations of the antiepileptic drugs is extremely useful, particularly
      in children and in patients who require associated antiepileptic medication.

PMID- 11317176
TI  - Epidemiology of ciprofloxacin-resistant Pseudomonas aeruginosa in a veterans
      affairs hospital.
AB  - This study was performed to identify risk factors for the nosocomial acquisition
      of ciprofloxacin-resistant Pseudomonas aeruginosa (CRPA) in a Veterans
      Administration hospital between January 1994, and March 1995. The study was a
      retrospective comparison of host factors and in-hospital exposures of patients
      who acquired nosocomially CRPA and ciprofloxacin-sensitive P. aeruginosa (CSPA).
      Participants included 42 adult patients with nosocomial CRPA acquisition and 52
      adult patients with nosocomial CSPA acquisition. Before pseudomonal acquisition,
      antecedent ciprofloxacin receipt (50% compared with 8%; odds ratio [OR], 12; p =
      0.001), the presence of an indwelling airway (36% compared to 17%; OR, 2.6; p =
      0.04), and documented antecedent infection (74% compared to 52%; OR, 2.6; p =
      0.03) were significantly associated with acquisition of CRPA. On multivariate
      analysis, antecedent ciprofloxacin receipt (OR, 16.8; p = 0.0001) and presence of
      an indwelling airway (OR, 10.5; p = 0.009) remain as significant associations.
      Furthermore, the test of significance confirmed synergy between these two
      factors. Antecedent ciprofloxacin therapy and indwelling airway act independently
      and synergistically to promote CRPA acquisition.

PMID- 11317177
TI  - Effects of pefloxacin on urinary and salivary concentrations of isoniazid in six
      healthy female volunteers.
AB  - The effects of pefloxacin (PFC), a fluoroquinolone antibiotic, on the urinary and
      salivary concentrations of Isoniazid (INH) were investigated in six healthy
      female volunteers 19 to 30 years of age. The presence of PFC increased the rate
      and extent of INH absorption and the rate of its excretion in the urine and
      saliva. There was an increase in the excretion rate constant (K) and a reduction
      in the half-life (t1/2) of INH in the presence of PFC. Four of the volunteers had
      t(1/2) values in the range of 1.55 to 2.43 hours and were considered to be fast
      acetylators, whereas two subjects with a t(1/2) in the range of 3.36 to 4.41
      hours were considered to be slow acetylators. Concurrent administration of INH
      and PFC may lead to an increased INH toxicity based on the results of the present
      study.

PMID- 11317178
TI  - Clopidogrel-induced mixed hepatocellular and cholestatic liver injury.
AB  - An 81-year-old woman developed symptomatic liver disease 3 weeks after beginning
      clopidogrel as adjunctive antiplatelet therapy for a coronary stent implantation.
      Symptomatic liver disease associated with short-term periprocedural
      administration of clopidogrel for coronary stenting has not been well described.
      The clinical significance of this event as well as a possible interaction between
      clopidogrel and other drugs metabolized by the cytochrome P450 2C9 pathways
      coadministered to this patient are discussed.

PMID- 11317179
TI  - Vancomycin anaphylaxis in a patient with vancomycin-induced red man syndrome.
AB  - Vancomycin is a powerful glycopeptide antibiotic that is increasingly being used
      owing to the emergence of highly resistant organisms such as methicillin
      resistant Staphylococcus aureus. Although a generally safe medication,
      administration of vancomycin is not benign, and there have been a number of
      adverse reactions reported. We present the case of a patient with vancomycin
      induced red man syndrome who developed vancomycin anaphylaxis. Our case
      illustrates that red man syndrome may be a marker for true vancomycin allergy,
      although it was generally not thought of as so in the past.

PMID- 11317180
TI  - Scleroderma lung: pathogenesis, evaluation, and current therapy.
AB  - Interstitial lung disease (ILD) is now the most common cause of mortality in
      scleroderma, although its pathogenesis remains poorly understood. Management
      requires early detection and treatment before the onset of lung fibrosis. In a
      number of uncontrolled studies, the combination of daily oral cyclophosphamide
      and low-dose prednisone appears to be effective, although these conclusions have
      yet to be confirmed.

PMID- 11317181
TI  - Sodium bicarbonate solution nebulization in the treatment of acute severe asthma.
AB  - This is a case report of a 15-year-old asthmatic girl who was admitted with a
      severe acute attack of bronchial asthma who eventually recovered, possibly with
      the help of sodium bicarbonate solution nebulization.

PMID- 11317182
TI  - Neurocardiogenic syncope with Addison's disease.

PMID- 11317183
TI  - Unusual distribution, pharmacokinetics, and metabolism of some drugs and their
      implications to pharmacotherapy.

PMID- 11317184
TI  - Treatment of stage I hypertension and development of renal dysfunction.

PMID- 11317185
TI  - Calcium channel blockers in hypertension: the debate reawakens.

PMID- 11317186
TI  - Blockade of the renin-angiotensin-aldosterone system with combination angiotensin
      receptor antagonist and ACE inhibitor therapy: observations from Val-HeFT and
      CALM.

PMID- 11317188
TI  - Does treatment of non-malignant hypertension reduce the incidence of renal
      dysfunction? A meta-analysis of 10 randomised, controlled trials.
AB  - OBJECTIVE: It remains controversial whether non-malignant 'benign' hypertension
      causes renal dysfunction. The effect of lowering blood pressure on the incidence
      of renal dysfunction among patients with non-malignant hypertension is not clear.
      This meta-analysis was conducted to determine whether antihypertensive drug
      therapy reduces the incidence of renal dysfunction in patients with non-malignant
      hypertension. METHODS: Randomised, controlled trials of antihypertensive drug
      therapy of more than 1 year duration that reported renal dysfunction as an
      outcome were identified through MEDLINE search and literature review. A random
      effects model was used to obtain summary estimates. RESULTS: Ten trials were
      identified, involving 26, 521 individuals and 114 000 person-years. All excluded
      subjects with advanced baseline renal disease. Definition of renal dysfunction
      outcome varied among trials but within each trial was applied similarly to both
      treatment and control groups. Drug treatment consisted mostly of diuretics and
      adrenergic blockers. Overall, treated patients had lower blood pressure and fewer
      cardiovascular events. There were a total of 317 cases of renal dysfunction.
      Patients randomised to antihypertensive therapy (or more intensive therapy) did
      not have a significant reduction in their risk of developing renal dysfunction
      (relative risk = 0.97; 95% confidence interval (CI) 0.78-1.21; P = 0.77).
      CONCLUSIONS: Among patients with non-malignant hypertension enrolled in
      randomised trials, treated patients did not have a lower risk of renal
      dysfunction. The 95% CI suggests that a 25% or more true protective effect of
      antihypertensive drugs is unlikely.

PMID- 11317187
TI  - Lipid second messenger regulation: the role of diacylglycerol kinases and their
      relevance to hypertension.
AB  - Extracellular stimuli elicit cellular responses through generation of
      intracellular second messengers. The lipid second messenger diacylglycerol is
      produced following activation of the phosphoinositide signalling system.
      Diacylglycerol is the physiological activator of protein kinase C but also
      interacts indirectly with other signalling molecules such as small G proteins.
      Diacylglycerol kinases convert diacylglycerol to phosphatidic acid so terminating
      signalling through diacylglycerol. However, phosphatidic acid itself has a lipid
      second messenger role, with targets distinct from those of its precursor
      diacylglycerol. Therefore, diacylglycerol kinases occupy a central position in
      signal transduction and regulation of their activity is crucial to cellular
      function. A family of nine mammalian diacylglycerol kinases have been identified.
      Their structural diversity and complex pattern of tissue expression suggests that
      they function in distinct cellular processes. In addition to the plasma membrane,
      diacylglycerol kinases are found at the nucleus and cytoskeleton and
      translocation between subcellular compartments occurs with agonist stimulation.
      In small arteries diacylglycerol kinase activity is increased by adrenergic
      stimulation implying a role in vascular smooth muscle responses. Due to their
      role as key regulators of protein kinase C activity diacylglycerol kinases may
      play a role in the cardiovascular changes that occur in hypertension and as such
      could represent novel therapeutic targets.

PMID- 11317189
TI  - Hypertension and its determinants among adults in high mountain villages of the
      Northern Areas of Pakistan.
AB  - We studied the prevalence and determinants of hypertension among adults in
      mountainous rural villages in the Ghizar district Northern Areas of Pakistan, an
      area that recently has undergone substantial economic development. We selected a
      stratified random sample of 4203 adults (age > 18 years) from 16 villages in
      Punial Valley of Ghizar district where the number of study subjects from each
      village was proportionate to the size of the village. We obtained blood pressure
      (BP) records by taking the mean of the second and third BP measurement, using a
      standard mercury sphygmomanometer, and assessed risk factors for hypertension in
      the study subjects. The mean +/- s.d. blood pressures (mm Hg) were 125 +/- 19
      systolic and 80 +/- 12 diastolic in men and 125 +/- 22 systolic and 78 +/- 14
      diastolic in women. The 125 +/- 22 systolic and 78 +/- 14 diastolic in women. The
      mm Hg, or systolic BP > or = 140 mm Hg or currently taking antihypertensive
      medication) was 15%, increasing from 4% in the 18-29 year age group to 36% among
      persons 60 years of age or older. The age-standardised prevalence of hypertension
      was 14% (12.5% among men and 14% among women). There was no significant
      difference in prevalence of hypertension in males, and in females. Multivariate
      analysis revealed that age, and higher body mass index (overweight and obesity)
      were independently associated with higher prevalence of hypertension. People with
      hypertension were more likely to have a first-degree relative with physician
      diagnosed hypertension (OR = 1.90, 95% CI 1.49, 2). Hypertension is a significant
      health problem in rural northern Pakistan. The primary health care programme in
      the Northern Areas of Pakistan needs to address this problem, especially
      identifying people at risk.

PMID- 11317190
TI  - The effect of a change in ambient temperature on blood pressure in normotensives.
AB  - The aim of this study was to investigate the influence of ambient temperature on
      blood pressure (BP). BP measurements were taken in 20 normotensive volunteers who
      stayed in Greenland for a 6-week period. Measurements of systolic (SBP),
      diastolic (DBP) and heart rate (HR) were taken before (3 sessions), during (7-8
      sessions) and after the journey (3 sessions). Each session consisted of five BP
      measurements in the supine position after at least 5 min rest. All five readings
      were averaged. Temperature data (mean +/- s.d.), collected from meteorological
      services, before, during and after Greenland were 15.7 +/- 0.6, 0.5 +/- 1.5 and
      8.2 +/- 0.8 degrees C. SBP values were 116 +/- 7.0, 122 +/- 7.6 and 116 +/- 7.4
      and DBP 63 +/- 5.2, 66 +/- 5.8 and 65 +/- 6.5 mm Hg, respectively. HR amounted to
      58 +/- 7.4, 61 +/- 6.7 and 60 +/- 7.4 bpm. Significant differences existed
      between, before and during for SBP and DBP and between, during and after for SBP.
      Readings were grouped in four categories based on the temperature at the time of
      reading. For SBP as well as DBP a clear dose-response relationship was
      demonstrated between low temperature and high BP, although for DBP only a few
      correlations were statistically significant. Mean correlation coefficients for
      SBP and DBP against temperature were -0.44 (P < 0.001) and -0.27 (P < 0.005),
      respectively. our results are in favour of a moderate, but both significant and
      relevant increase in sbp and dbp when moving from higher to lower ambient
      temperature.

PMID- 11317191
TI  - Aldosterone to renin ratio as a determinant of exercise blood pressure response
      in hypertensive patients.
AB  - Aldosterone to renin ratio (ARR) is a marker of inappropriate aldosterone
      activity in hypertension. Since aldosterone may adversely affect vascular
      compliance, we hypothesised that the ARR would relate to exercise blood pressure
      (BP) responses in hypertension. Blood sampling was done in untreated
      hypertensives for plasma renin activity (PRA, ng/mL/hr) and plasma aldosterone
      (PA, pmol/L). ARR was derived by dividing the PA value by the PRA value, and this
      index was normalised by natural logarithm (lnARR) for further analyses. Each
      patient underwent 24-h ambulatory BP (ABP), and a 3-min submaximal exercise test
      using the Dundee Step Test. The Spearman rank correlation coefficients between
      lnARR and office BP (OBP), ABP and exercise BPs and BP changes estimated during
      exercise were assessed. A total of 119 (66 males) hypertensive subjects aged 48
      (s.d. 12) years were studied. The respective OBP, ABP, exercise BP and the change
      in exercise BP were 167(23)/105(11), 140(15)/87(10), 189(26)/107(12) and
      25(15)/2(9) mmHg. lnARR was significantly correlated with exercise systolic BP (r
      = 0.24, P < 0.001), exercise diastolic bp (r = 0.23, P < 0.05), systolic abp (r =
      0.22, P < 0.05) and systolic obp (r = 0.19, P < 0.05). in a multiple regressional
      analysis controlling for age and sex and all other bp measurements to assess the
      relative strengths of correlation between all the bp indices with lnarr, only
      exercise systolic bp (P = 0.012) and the change in systolic BP during exercise
      (negatively, P = 0.013) emerged as significant independent predictors of lnARR.
      In conclusion, there was an independent and significant correlation between ARR
      and exercise systolic BP.

PMID- 11317192
TI  - A common mutation of low-density lipoprotein receptor gene is associated with
      essential hypertension among Japanese.
AB  - Candidate genes offer one approach to the identification of the genetic
      susceptibility to hypertension. A common gene variant of the low-density
      lipoprotein (LDL) receptor gene (LDLR) that affects plasma LDL metabolism within
      the normolipidaemic range, may be such a candidate gene. A common mutation of
      LDLR, C1773T, was associated with lipid metabolism such that the T1773 allele
      increased plasma LDL levels in a Caucasian population. The present study examined
      whether C1773T/LDLR was associated with essential hypertension in a Japanese
      population. Subjects with essential hypertension (EHT, n = 300) with a family
      history of hypertension, and controls (NT, n = 310, sex- and age-matched with
      EHT) were recruited from among out-patients at Osaka University Hospital. A
      C1773T substitution at codon 570 in LDLR was determined using PCR-Hinc II-RFLP.
      It was revealed that the C1773 allele was significantly more frequent (0.89)
      among hypertensive patients (chi2 = 9.58, P < 0.01) than normotensives (0.83),
      the calculated odds ratio being 1.7 (95% CI: 1.2-2.4). The effect of the T1773
      allele on increasing cholesterol was significant in normotensives without
      antihyperlipidaemic medication, but not in hypertensives. After adjustments of
      confounding factors, the estimated odds ratio for hypertension in the subjects
      with C1773 homozygote increased to 2.1 (95% CI: 1.3-3.5), suggesting that this
      polymorphism is an independent risk factor for hypertension. Our results show
      that the C1773 mutant of LDLR increases susceptibility to hypertension, but not
      via hypercholesterolaemia.

PMID- 11317193
TI  - Evaluation of normal and large sphygmomanometer cuffs using the Omron 705CP.
AB  - Sphygmomanometers are usually sold with a single cuff though some are supplied
      with a short cuff as standard and offer a longer one for larger arms. However,
      data on the differences in measurements taken with different cuffs applied to
      different sized arms are conflicting and this study set out to investigate the
      difference between those taken with 'normal' and 'large' cuffs in arms 28 cm or
      more in circumference. We avoided observer error by using a semi-automatic
      digital sphygmomanometer, the Omron 705CP. The 22 subjects employed were selected
      from one general practice as having a range of previous office blood pressures
      and a variety of arm sizes above 28 cm in circumference. Omron 'normal' and
      'large' cuffs were used alternately, taking five blood pressures with each to a
      total of 30 readings per patient, resulting in 660 readings, 330 with each cuff.
      There were mean systolic/diastolic differences of 2.7/3.8 (s.d.s 4.7/2.8) for all
      subjects. These were greater in the normotensive. When divided into two groups
      with systolic blood pressures below and equal to or above 140 mm Hg, differences
      were -1.9/3.0 to 7.1/4.7. From the results of the study, we recommend that large
      cuffs should be used for all patients with an arm circumference of 28 cm or above
      but the Omron large cuff still requires formal validation.

PMID- 11317194
TI  - Chronotherapeutic delivery of verapamil in obese versus non-obese patients with
      essential hypertension.
AB  - BACKGROUND: The effect of controlled-onset, extended-release (COER) verapamil on
      haemodynamic parameters in obese and non-obese patients is evaluated in this
      analysis. METHODS: Data were pooled from three clinical trials evaluating
      efficacy and tolerability of COER-verapamil. Hypertensive men and women (stage I
      to III) were randomised to COER-verapamil (180-540 mg at bedtime) or placebo for
      4-8 weeks and stratified according to body mass index (BMI-obese > 28 kg/m2).
      Efficacy was assessed as change from baseline in blood pressure (BP), heart rate,
      and rate-pressure product during four time periods throughout the dosing
      interval. Safety and tolerability were assessed by monitoring all adverse events
      and changes in metabolic laboratory parameters. RESULTS: Reductions in all
      haemodynamic parameters were significantly greater following COER-verapamil
      compared with placebo for all time periods. The haemodynamic effects of COER
      verapamil in obese (n = 166, BMI = 32.8 kg/m2) and non-obese patients (n = 115,
      BMI = 25.0 kg/m2) were similar. COER-verapamil was well tolerated in both
      subgroups, but the incidence of constipation was significantly less in obese
      patients (P < 0.001). CONCLUSIONS: COER-verapamil is effective in reducing BP,
      heart rate, and rate-pressure product independently of BMI.

PMID- 11317195
TI  - Renovascular hypertension and focal segmental glomerulosclerosis in the
      contralateral kidney.

PMID- 11317196
TI  - Where is the evidence that radial artery tonometry can be used with a generalised
      transfer function to accurately and non-invasively predict central aortic blood
      pressure?

PMID- 11317197
TI  - ACE inhibitors for all--'Hope' for the heart and failure for the kidneys?

PMID- 11317198
TI  - Using medication history to measure confounding by indication in assessing
      calcium channel blockers and other antihypertensive therapy.
AB  - Reported findings of elevated risk of adverse events associated with calcium
      channel blocker use in hypertensives may be due partly to unmeasured confounding
      by indication. To determine if such confounding occurs, we conducted a
      retrospective cohort analysis of 77 196 Pennsylvania Medicaid recipients aged 18
      to 61 who were treated with antihypertensive medication between 1990 and 1992.
      All diagnoses and dispensed prescriptions during the year prior to study entry
      were examined. Prior recipients of multitherapy (n = 18 763) were more likely to
      have had previously diagnosed risk factors (OR = 1.31 [95% CI, 1.30-1.33]) than
      subjects with prior monotherapy (n = 11141). New initiators (n = 47292) were less
      likely to have had previously diagnosed risk factors (OR = 0.48 (95% CI, 0.47
      0.49)) than previous users (n = 29904). The likelihood of being prescribed
      calcium channel blocker rather than other monotherapy was significantly higher
      for subjects diagnosed during the previous week with arteriosclerotic
      cardiovascular disease OR = 7.78 (95% CI, 2.72-22.28), P < 0.0001; angina OR =
      2.92 (95% CI, 1.77-4.83), (P < 0.0001); diabetes OR = 1.49 (95% CI, 1.07-2.06),
      (P = 0.0004); and hypertension OR = 1.57 (95% CI 1.35-1.82), (P < 0.0001).
      Calcium channel blockers were selectively prescribed to subjects at elevated risk
      of adverse events. Confounding by indication was found in this large indigent
      population. Unmeasured confounding may contribute to overestimated relative risk
      of adverse events associated with calcium channel blocker therapy vs diuretics or
      beta-blockers. At least 1 full year of subjects' medical and prescription drug
      history should be examined prior to study entry; shorter observation periods will
      miss clinically relevant information about risk.

PMID- 11317199
TI  - A randomised, placebo-controlled, double-blind, crossover study of losartan and
      enalapril in patients with essential hypertension.
AB  - The primary objective of this randomised, placebo- controlled, double-blind,
      crossover study, was to evaluate and compare the longer term effects of the
      angiotensin II type 1 receptor antagonist losartan and the converting enzyme
      inhibitor enalapril on 24-h ambulatory blood pressure (BP). After a 4-week
      placebo run-in period, nine patients with essential hypertension entered the
      double-blind phase of the study, which consisted of three 6-week periods during
      which patients were treated with placebo, enalapril 20 mg o.d. or losartan 50 mg
      o.d. Losartan and enalapril, taken between 07.00 and 08.00, reduced ambulatory BP
      throughout the 24-h period. Average night time BP was reduced from 133/85 mm Hg
      on placebo to 124/78 mm Hg on enalapril and to 126/77 mm Hg on losartan. Daytime
      BP averaged 157/101 mm Hg on placebo, and was significantly lower during
      enalapril (142/91 mm Hg) than during losartan treatment (147/95 mm Hg). Clinic
      BP, measured 2 to 4 hours after drug intake, was reduced to the same extent by
      both drugs. The losartan-induced BP changes were significantly related to those
      obtained with enalapril (0.63 < r < 0.93). Ambulatory BP monitoring was repeated
      after 4 weeks of combined therapy in six patients. The BP lowering effect of the
      combination was not significantly better than that achieved with enalapril alone.
      In conclusion, losartan 50 mg o.d. and enalapril 20 mg o.d. lower BP to
      approximately the same extent, except for a more pronounced effect of enalapril
      on daytime ambulatory BP. The current study does not provide convincing evidence
      that addition of losartan to enalapril in the doses used further reduces BP.

PMID- 11317200
TI  - Exercise blood pressure correlates with the maximum heart rate corrected QT
      interval in hypertension.
AB  - Submaximal exercise systolic blood pressure (ExSBP) is a recognised predictor of
      cardiac mortality. This study examined the possibility that this might be related
      to increased QT dispersion or prolonged maximum QT(c) interval (QTcmax). Twenty
      nine untreated hypertensive subjects were assessed. Each subject underwent an
      echocardiographic examination and a 24-h ambulatory blood pressure (ABP). ExSBP
      was measured during a 3-min lightweight submaximal Dundee step test. In multiple
      regressional analyses, only left ventricular mass index significantly predicted
      QT dispersion (R2 = 22.4%, P = 0.018) and QT(c) dispersion (R(2) = 25.3%, P =
      0.012). However, with respect to QTcmax, ExSBP (R2 = 21.6%, P = 0.02) emerged as
      the sole significant predictor of this index. Five (17.2%) out of the 29 subjects
      had prolonged QTcmax > or = 430 ms and these subjects were not differentiated by
      24-h ABP (146 (s.d. 21)/83 (16) vs 140 (14)/88 (11) mm Hg, P = Ns) but by ExSBP
      (226 (15) vs 188 (24) mm Hg, P = 0.002). In conclusion, systolic blood pressure
      measured during exercise correlated with QT(c) max in hypertension. This finding
      may partly explain the prognostic value of exercise blood pressure.

PMID- 11317201
TI  - Is random screening of value in detecting glucocorticoid-remediable aldosteronism
      within a hypertensive population?
AB  - INTRODUCTION: Glucocorticoid-remediable aldosteronism (GRA) is a rare inherited
      cause for hypertension associated with a significant morbidity and mortality at
      an early age. Individuals with this abnormality frequently present with severe
      hypertension which is resistant to standard antihypertensive therapy, a strong
      family history of hypertension, intracranial haemorrhage, and sporadic
      hypokalaemia. However many affected individuals may appear phenotypically
      indistinguishable from normal essential hypertensives but remain at high risk of
      morbidity and mortality. OBJECTIVE: To determine how effective random or targeted
      screening of hypertensive patients is for the detection of GRA. DESIGN: A
      prospective study involving the screening of 300 hypertensive patients chosen at
      random attending the Aberdeen Hypertension Clinic and, during the same period,
      the targeted screening of patients with a medical and family history suggestive
      of GRA. SETTING: A University hospital with a primary catchment of 500,000
      inhabitants and a hypertension clinic population of over 8500 patients. RESULTS:
      Random screening failed to identify any GRA mutation-positive individuals.
      Targeted screening of selected individuals revealed two index families and four
      further families containing 40 mutation-positive individuals. CONCLUSION:
      Targeted screening of hypertensive individuals with a family history of
      hypertension, cerebral haemorrhage, a history of hypertension from an early age,
      resistant hypertension which has proven difficult to control and hypokalaemia
      revealed two index cases and four further individuals and 30 hypertensive and 10
      normotensive members of their families with GRA.

PMID- 11317202
TI  - The Haemodynamic Instability Score (HIS) for assessment of cardiovascular
      reactivity in hypertensive and normotensive patients.
AB  - The normal response to postural challenge is characterised by maintenance of
      relatively stable blood pressure (BP) and heart rate (HR) after 30 sec to 30 min
      of head-up tilt. The objective of the present study was to determine the degree
      of instability of cardiovascular responses to postural challenge in normotensive
      and hypertensive subjects. In the initial phase of the study, two groups of age
      and sex-matched subjects were assessed: essential hypertension (n = 20) and
      healthy (n = 37). The BP and HR were recorded at 5-min intervals during the
      course of the 10-min supine-30-min head-up tilt test (HUTT). We categorised 'BP
      change' as the difference between individual BP measurements during HUTT and the
      last recumbent BP value, divided by latter value. The average and standard
      deviation (SD) of the recorded BP changes were calculated, and BP changes were
      plotted along a time curve. A computerised image analyser then calculated the
      outline ratio (OR) and fractal dimension (FD) values for each of the curves. An
      identical process evaluated measurements for HR-changes. BP- and HR-changes were
      then converted into absolute numbers, and the average, SD, OR, and FD were
      calculated. A multivariate analysis was conducted, evaluating independent
      predictors of hypertension. Finally, an equation for the calculation of
      'haemodynamic instability score' (HIS) was deduced and a cut-off between HIS of
      hypertensive and normotensive subjects was established. Independent predictors of
      the cardiovascular response to postural challenge of hypertensives (Group I) vs
      healthy (Group II) were: a.DIAST-FD, a.HR-AVG, a.HR-SD, a.HR-FD, DIAS-SD and HR
      SD and HR-SD. Based on these five predictors, a linear discriminant score was
      computed and called the Haemodynamic Instability Score (HIS): HIS = 59.4 + (
      16.6*a.DIAST-FD) + (-29.0*a.HR-AVG) + (-82.4*a.HR-SD) + (-30.1*a.HR-FD) + (
      57.9*DIAS-SD) + (73.4*HR-SD) The HIS values in Group I (hypertensives) were: avg
      = 3.348, SD = 2.863, and 95% CI for mean = 2.008, 4.688. The HIS values in Group
      II (healthy) were: avg = -3.394, SD = 2.435, 95% CI for mean = -4.206, -2.582.
      Values of the HIS > -2.09 were generally observed in hypertensives (sensitivity
      95%) and values < or = -2.09 were usually seen in the healthy (specificity
      81.1%). The HIS was cross-validated in an additional group of hypertensive
      patients (n = 73). In the latter group, the HIS values were: avg = -0.456, SD =
      4.403, 95% CI for mean = -1.506, 0.593 and 71.4% sensitivity at the proposed cut
      off point. In conclusion, the HIS confers numerical expression to the degree of
      lability of BP and HR during postural challenge. Based on this score, a
      distinction between the cardiovascular reactivity of hypertensives vs
      normotensives is drawn. Possible applications of HIS are discussed.

PMID- 11317203
TI  - Polymorphisms of the renin-angiotensin system in patients with multifocal renal
      arterial fibromuscular dysplasia.
AB  - Fibromuscular dysplasia (FMD) is an important cause of renal artery stenosis,
      particularly in young females. Polymorphisms of the renin-angiotensin (RA) system
      have been implicated in the pathogenesis of hypertension and atherosclerotic
      vascular disease, and may play a role in the development of FMD. Examination of
      polymorphisms by PCR for angiotensin-converting enzyme (ACE) I/D, angiotensin II
      type 1 receptor (AT1R) A1166C and angiotensinogen (AGT) M235T and T174M was
      undertaken in 43 patients with typical multifocal renal arterial FMD (MF-FMD) and
      in 89 controls. The age of MF-FMD patients at the time of diagnosis of
      hypertension did not differ (38.6 + 11.1 years vs 35.5 +/- 10.3 years, P = 0.12)
      from controls and the proportion (95% vs 86%, P = 0.14) of females was similar.
      Allele frequencies did not differ significantly between groups, except that MF
      FMD patients had a significantly higher frequency of the ACE I allele than
      control subjects (0.62 vs 0.47, P = 0.026). Since the ACE I allele is associated
      with lower circulating ACE levels and possibly lower tissue levels of angiotensin
      II (Ang II), and since Ang II modulates vascular smooth muscle cell growth and
      synthetic activity, the I allele might predispose to defective remodelling of the
      arterial media, and thus to the development of MF-FMD. This contrasts with
      atherosclerotic renal artery stenosis, coronary stent restenosis and carotid
      intimal thickening, which are diseases affecting the arterial intima, and which
      are associated with increased frequency of the D allele.

PMID- 11317204
TI  - Validation of the Welch Allyn 'Vital Signs' oscillometric blood pressure monitor.
AB  - This study has determined the accuracy of the Welch Allyn 'Vital Signs' blood
      pressure (BP) monitoring device in an adult population, according to the criteria
      of the British Hypertension Society (British Hypertension Society, 1993).
      Validation was also classified by the American 'Association for the Advancement
      of Medical Instrumentation' (AAMI). The Welch Allyn 'Vital Signs' monitor
      achieved a BHS grade A for both systolic and diastolic BP. It also met the
      criteria for the AAMI protocol. The mean differences between trained observers
      using a mercury sphygmomanometer and the device were -1 +/- 5 mm Hg for systolic
      BP and -3 +/- 4 mm Hg for diastolic BP. The Welch Allyn 'Vital Signs' monitor can
      be recommended for clinical use in the adult population. This is one of the first
      oscillometric monitors designed for routine use in a hospital environment that
      has been found to provide an accurate assessment of BP by accepted validation
      procedures.

PMID- 11317205
TI  - A clinical study of the Korotkoff phases of blood pressure in children.
AB  - BACKGROUND: Five Korotkoff phases are described in adults, but there are no
      studies of the Korotkoff phase distribution in children. This study determines
      the presence and length of Korotkoff phases in children, providing data on the
      repeatability of these measurements, the relationship between the phases, and
      finally the relationship between the phases and heart rate, blood pressure and
      arm circumference. METHODS: Seventy, 11-year-old children were studied. The
      Korotkoff sounds were recorded from the bell of a stethoscope to a MiniDisc
      system and each sound described twice on separate occasions as phase I, II, III
      or IV, with phase V meaning disappearance of the sound. RESULTS: Phases I, II,
      III, IV and V were present in 97% (68/70), 61% (43/70), 51% (36/70), 88% (62/70)
      and 80% (56/70) respectively. When the recordings were blindly re-assessed there
      was no significant difference in the phase distribution of the sounds. All five
      phases were present in 40% (28/70). Phase III only occurred in the presence of
      phase II (P < 0.0001). There was no significant relationship between the presence
      of the different phases and heart rate or blood pressure. Arm circumference was
      significantly larger in children with phase V present (P < 0.02). CONCLUSIONS:
      The Korotkoff sounds and phase distribution present in normal children is
      described. Korotkoff sounds were consistently allocated to the various Korotkoff
      phases. This study provides insights into the problems of accurate diastolic
      blood pressure measurement. Phase V was more likely to be present with increasing
      arm circumference, but the variation in the occurrence of phases II and III
      remains unexplained.

PMID- 11317206
TI  - Doxazosin, an alpha1-adrenoceptor antagonist, inhibits serotonin-induced shape
      change in human platelets.
AB  - Patients with peripheral vascular disease or diabetes mellitus tend to have
      elevated circulating levels of naturally occurring platelet agonists like
      serotonin (5 hydroxytryptamine; 5-HT). This bioamine can induce platelet shape
      change (PSC) an early phase of platelet activation, which is essentially aspirin
      resistant. In addition, 5-HT exerts other harmful effects (eg stimulating
      vascular smooth muscle proliferation and inducing vasoconstriction in
      atheromatous coronary vessels). The aim of this study was to determine whether
      doxazosin inhibits 5-HT-induced PSC. Doxazosin is a long acting alpha(1)
      adrenoceptor antagonist, used in the treatment of essential hypertension and/or
      benign prostatic hyperplasia (BPH). Platelet rich plasma (PRP) was prepared from
      healthy volunteers (n = 8; five males and three females with a median age of 32
      years, range: 26-57). Agonists (5-HT, 0.06-0.5; ADP, 0.1-0.2 micromol/l or
      U46619, a TXA(2)analogue, 0.025-0.05 micromol/l) were added to PRP and aliquots
      were removed at specific time points for median platelet volume (MPV) measurement
      (using a high-resolution channelyser). The MPV was used as an indicator of PSC.
      PRP was also incubated with doxazosin (final concentration: 0.33 microM, a
      concentration similar to therapeutic plasma levels) prior to the addition of each
      of the above-mentioned agonists. Doxazosin significantly inhibited (P = 0.007 and
      P = 0.008, at 30 sec and 60 sec, respectively) the 5-HT-induced increase in MPV.
      Doxazosin did not significantly inhibit ADP- or U46619-induced PSC. The
      inhibitory effect of doxazosin seems to be specific to platelet 5-HT(2)
      receptors, since there was no effect on ADP- or U46619-induced PSC. This
      inhibition of platelet activation may be an additional, clinically relevant,
      advantage. Future in vivo studies should consider assessing the effect of
      doxazosin on 5-HT-induced platelet activation.

PMID- 11317207
TI  - Metastatic phaeochromocytoma: risks of diagnostic needle puncture and treatment
      by arterial embolisation.
AB  - A 62-year-old man had an acute episode of hypertension 72 h after fine needle
      aspiration biopsy of an intra- hepatic nodule. The patient had been operated 3
      years previously for a right adrenal phaeochromocytoma with no evidence of
      metastases at that time. Thus, a relapse of the tumour was postulated and
      confirmed by raised levels of urinary metanephrines. The extent of the metastases
      precluded surgical intervention and thus localised embolisation was proposed and
      permitted a clinical stabilisation over 8 months. This case indicates the
      necessity of long-term post-operative follow-up of phaeochromocytoma as well as
      the dangers of fine needle aspiration biopsy of metastases from this kind of
      tumour. Treatment of malignant phaeochromocytoma is difficult and embolisation
      was a useful therapeutic alternative in this case where the metastases were well
      defined.

PMID- 11317208
TI  - Reduced heat shock proteins--a mechanism to explain higher cardiovascular events
      associated with doxazosin.

PMID- 11317210
TI  - Spectroscopic brain mapping the N-acetyl aspartate to cognitive-perceptual states
      in chronic pain.

PMID- 11317211
TI  - Association analysis of G-protein beta 3 subunit gene with altered Ca(2+)
      homeostasis in bipolar disorder.

PMID- 11317212
TI  - Suicide and the serotonin transporter gene.

PMID- 11317213
TI  - Reelin mutations in mouse and man: from reeler mouse to schizophrenia, mood
      disorders, autism and lissencephaly.

PMID- 11317214
TI  - Extrapyramidal symptoms and antidepressant drugs: neuropharmacological aspects of
      a frequent interaction in the elderly.
AB  - Depression is the most prevalent functional psychiatric disorder in late life.
      The problem of motor disorders associated with antidepressant use is relevant in
      the elderly. Elderly people are physically more frail and more likely to be
      suffering from physical illness, and any drug given may exacerbate pre-existing
      diseases, or interact with other drug treatments being administered for physical
      conditions. Antidepressants have been reported to induce extrapyramidal symptoms,
      including parkinsonism. These observations prompted us to review the
      neurobiological mechanism that may be involved in this complex interplay
      including neurotransmitters and neuronal circuits involved in movement and
      emotion control and their changes related to aging and disease. The study of the
      correlations between motor and mood disorders and their putative biochemical
      bases, as presented in this review, provide a rationale either to understand or
      to foresee motor side effects for psychotropic drugs, in particular
      antidepressants.

PMID- 11317215
TI  - The search for complex disease genes: fault by linkage or fault by association?
AB  - With the human DNA sequence nearing completion, the search for complex disease
      genes is gaining momentum, as is the debate over gene-finding strategies. This
      overview contrasts two pivotal methods: linkage analysis and association mapping.
      Linkage analysis has been used successfully to identify the genes underlying rare
      mendelian disorders. It has also played a role in attempts to map genes for
      common non-mendelian (also known as 'complex' or 'multifactorial') diseases such
      as psychiatric disorders. However, despite extensive efforts progress has been
      slow, marred by inconsistent or ambiguous results. Uncertainties about the
      utility of the linkage approach for complex genetic traits has spurred interest
      in association studies with candidate genes, as an alternate strategy. Recently,
      with the advent of new molecular tools, in particular high-density, single
      nucleotide polymorphisms (SNPs) maps, it has been argued that, while linkage
      analysis may retain some role, genome-wide association studies with SNPs offer a
      superior strategy for unraveling genetic complexity. In this paper I review these
      issues, stressing the pros and cons of the various strategies. I propose that:
      (1) the uncertainties in association studies may have been underestimated; (2)
      neither method is sufficient or optimal; and (3) a joint linkage and association
      approach, together with genomic, statistical and computational advances, may have
      greater promise for understanding the genetic underpinnings of complex disorders
      in the new millennium.

PMID- 11317216
TI  - Reelin gene alleles and haplotypes as a factor predisposing to autistic disorder.
AB  - Autistic disorder (MIM 209850) is currently viewed as a neurodevelopmental
      disease. Reelin plays a pivotal role in the development of laminar structures
      including the cerebral cortex, hippocampus, cerebellum and of several brainstem
      nuclei. Neuroanatomical evidence is consistent with Reelin involvement in
      autistic disorder. In this study, we describe several polymorphisms identified
      using RNA-SSCP and DNA sequencing. Association and linkage were assessed
      comparing 95 Italian patients to 186 ethnically-matched controls, and using the
      transmission/disequilibrium test and haplotype-based haplotype relative risk in
      172 complete trios from 165 families collected in Italy and in the USA. Both case
      control and family-based analyses yield a significant association between
      autistic disorder and a polymorphic GGC repeat located immediately 5' of the
      reelin gene (RELN) ATG initiator codon, as well as with specific haplotypes
      formed by this polymorphism with two single-base substitutions located in a
      splice junction in exon 6 and within exon 50. Triplet repeats located in 5'
      untranslated regions (5'UTRs) are indicative of strong transcriptional
      regulation. Our findings suggest that longer triplet repeats in the 5'UTR of the
      RELN gene confer vulnerability to autistic disorder.

PMID- 11317217
TI  - Genomic organization of the SLC1A1/EAAC1 gene and mutation screening in early
      onset obsessive-compulsive disorder.
AB  - The first genome scan conducted in early-onset obsessive-compulsive disorder used
      a non-parametric analysis to identify a peak in a region of chromosome 9
      containing the gene SLC1A1, which codes for the neuronal and epithelial glutamate
      transporter EAAC1. Interaction between the glutamatergic and serotonergic systems
      within the striatum suggests EAAC1 as a functional candidate in OCD as well. We
      determined the genomic organization of SLC1A1 primarily by using primers designed
      from cDNA sequence to amplify from adaptor-ligated genomic DNA restriction
      fragments. In order to confirm SLC1A1 as a positional candidate in early-onset
      OCD, common single nucleotide polymorphisms (SNPs) were identified that enabled
      mapping of SLC1A1 within the region of the lod score peak. Based on the linkage
      evidence, the coding region was sequenced in the probands of the seven families
      included in the genome scan. No evidence was found for a functional mutation, but
      several SNPs were identified. Capillary electrophoresis SSCP typing of a
      haplotype consisting of two common SNPs within EAAC1 revealed no significant
      linkage disequilibrium.

PMID- 11317218
TI  - An in-frame deletion in the alpha(2C) adrenergic receptor is common in African-
      Americans.
AB  - alpha(2) adrenergic receptors are activated by adrenaline and noradrenaline, and
      three subtypes (ie, A, B, C) have differential affinities for antagonists and
      medications. The alpha(2c) adrenergic receptor (ADRA2C), located on chromosome
      4p16.3, is a candidate gene for schizophrenia because it binds clozapine, an
      atypical neuroleptic useful for treatment-resistant schizophrenia. In addition,
      ADRA2C binds clonidine which is prescribed for three psychiatric diseases. This
      report communicates the findings of the genetic scanning of this gene of very
      tough GC content. The complete coding sequences and splice junctions were scanned
      with [DOVAM]-S in 104 schizophrenics, and pilot probes of patients with
      alcoholism (41 patients), cocaine abuse (25 patients), puerperal psychosis (30
      patients), attention deficient/hyperactivity disorder (25 patients) and autism
      (25 patients). Six sequence variants were found, including five silent
      polymorphisms (allele frequencies 0.6--25%) and an in-frame deletion of a
      homologous repeat at nucleotides 967--978 (ie, TIDRU(1)). Genotyping of the
      normal two repeat unit of the Third Intracytoplasmic Domain Repeat Unit
      (TIDRU(2)) and the deleted variant (TIDRU(1)) revealed that TIDRU(1) had allelic
      frequencies of 39% (11/28) and 3.5% (6/172) in African-American and Caucasian
      schizophrenics, respectively, and it occurred with equal frequency in controls
      (44%, 31/70 and 3.0%, 6/198). TIDRU(1) occurs at a location similar to the third
      intracytoplasmic 48-nucleotide repeat unit in the DRD4 that is associated with
      ADHD. Although these data do not suggest an association of TIDRU(1) with
      schizophrenia, additional studies are needed to see whether TIDRU(1) confers a
      clinical phenotype.

PMID- 11317219
TI  - Genomic structure and localisation within a linkage hotspot of Disrupted In
      Schizophrenia 1, a gene disrupted by a translocation segregating with
      schizophrenia.
AB  - Two overlapping and antiparallel genes on chromosome 1, Disrupted In
      Schizophrenia 1 and 2 (DISC1 and DISC2), are disrupted by a (1;11)(q42.1;q14.3)
      translocation which segregates with schizophrenia through at least four
      generations of a large Scottish family. Consequently, these genes are worthy of
      further investigation as candidate genes potentially involved in the aetiology of
      major psychiatric illness. We have constructed a contiguous clone map of PACs and
      cosmids extending across at least 400 kb of the chromosome 1 translocation
      breakpoint region and this has provided the basis for examination of the genomic
      structure of DISC1. The gene consists of thirteen exons, estimated to extend
      across at least 300 kb of DNA. The antisense gene DISC2 overlaps with exon 9.
      Exon 11 contains an alternative splice site that removes 66 nucleotides from the
      open reading frame. The final intron of DISC1 belongs to the rare AT-AC class of
      introns. We have also mapped marker DIS251 in close proximity to DISC1,
      localising the gene within a critical region identified by several independent
      studies. Information regarding the structure of the DISC1 gene will facilitate
      assessment of its involvement in the aetiology of major mental illness in
      psychotic individuals unrelated to carriers of the translocation.

PMID- 11317220
TI  - Serotonin transporter polymorphisms: no association with response to
      antipsychotic treatment, but associations with the schizoparanoid and residual
      subtypes of schizophrenia.
AB  - The human serotonin transporter gene (5-HTT) demonstrates two polymorphisms with
      possible functional impact: a 44-bp insertion/deletion polymorphism of the
      promoter region and a 17-bp variable number of tandem repeat polymorphism (VNTR)
      in intron 2 (STin2). Such genetic polymorphisms in the serotoninergic system may
      increase the susceptibility to schizophrenia or may serve as predictors of
      therapeutic response. We therefore analyzed these polymorphisms as susceptibility
      factors for schizophrenia by comparison of 684 schizophrenic inpatients with 587
      healthy controls. We furthermore compared the therapeutic outcome of
      schizophrenic patients differentiated by the 5-HTT genotypes. Schizo-affective
      patients were more frequently homozygous for the 44-bp insertion allele (Odds
      ratio, OR: 1.6, 95% confidence interval, CI: 1.1--2.3, P < 0.03) than were all
      other schizophrenic patients and controls. The 17-bp VNTR alleles found were:
      STin2.7, 9, 10, and 12. Sequence analysis revealed seven different sequence
      motifs with an invariable arrangement. Patients with schizo-paranoid
      schizophrenia were more frequently homozygous for the STin2.12 allele than were
      controls (OR: 1.4, CI: 1.1--1.8, P < 0.007) and all other schizophrenic patients
      (OR: 1.6, CI: 1.2--2.3). The STin2.9 allele represented a risk factor for the
      residual subtype of schizophrenia (OR: 6.4, CI: 2.5--16.2, P < 0.001). On the
      basis of global clinical impressions, as well as measurements with the positive
      and negative syndrome scale we found no association of the polymorphisms with
      therapeutic response. In conclusion, the 44-bp polymorphism may be associated
      with the schizo-affective and the 17-bp VNTR with the residual and schizo
      paranoid subtype of schizophrenia, findings which require further biochemical and
      epidemiological confirmation.

PMID- 11317221
TI  - Structure and polymorphisms of the human metabotropic glutamate receptor type 2
      gene (GRM2): analysis of association with schizophrenia.
AB  - Metabotropic glutamate receptors (mGluRs) belong to the class of GTP-binding
      protein coupled receptors and consist of eight different subtypes. The subtype 2
      metabotropic glutamate receptor (mGluR2) gene (GRM2) is one of the possible
      candidate genes for schizophrenia. Phencyclidine (PCP)-induced increase in
      glutamate efflux and schizophrenia-like behavioral abnormalities were reduced by
      pretreatment of the mGluRII agonist LY354740 in rats and its effects are mediated
      via mGluR2. To evaluate involvement of the mGluR2 gene in the pathogenesis of
      schizophrenia, we isolated the human mGluR2 gene and determined the transcription
      initiation site, the entire nucleotide sequence and the chromosomal localization.
      The hmGluR2 gene spans 13 kb with six exons, including one non-coding exon. The
      gene was mapped to chromosome 3 p12-p11 by Radiation Hybrid Panel analysis. We
      screened polymorphisms in the coding exons of the mGluR2 gene, using the SSCP
      procedure. The thirteen polymorphisms identified included ten missense, one
      silent mutation and two one-base substitutions in the 5'-untranslated region. We
      genotyped 213 Japanese schizophrenics and 220 controls to study the association
      of polymorphisms in the mGluR2 gene with schizophrenia. As we found no
      statistically significant differences in allele frequencies of each polymorphism,
      these polymorphisms apparently do not play a major role in schizophrenia.

PMID- 11317222
TI  - Polymorphism in SNAP29 gene promoter region associated with schizophrenia.
AB  - Linkage studies indicate that chromosome 22q contains a locus, or loci, for
      schizophrenia (SZ) and bipolar disorder (BPD). Furthermore, the congenital
      disorder velo cardio facial syndrome (VCFS), which is usually caused by a 22q11
      microdeletion, is associated with an increased prevalence of psychiatric disease,
      including SZ and BPD. One plausible candidate gene that maps to 22q11, in a
      region deleted in the most common form of VCFS, is SNAP29, a member of the SNAP
      25 family of SNARE proteins. To search for possible functional mutations in
      SNAP29 that could be analyzed as candidates for 22q11-linked psychiatric
      problems, exons, intron-exon junctions and the promoter region were screened. No
      coding variants were found, although a silent mutation at codon 6 and three
      single nucleotide polymorphisms (SNPs) were identified in the 5' untranslated and
      promoter regions. One SNP, an A-->G transition 923 [corrected] nucleotides
      upstream of the transcription start site, showed a moderately significant
      difference in the distribution of alleles and genotypes in patients with SZ
      compared with controls (allele frequency: chi(2) = 5.57, 1 df, P = 0.018;
      genotype: chi(2) = 9.49, 2 df, P = 0.009; odds ratio = 1.59, 95% Cl = 1.08-
      2.34). No significant difference was found in patients with BPD. Although the
      functional significance of this mutation is not known, the tetranucleotide core
      sequence of the ets and IK2 families of transcription factors is altered as a
      result of the SNP. These data suggest that a mutation in the SNAP29 gene promoter
      region, or a mutation in linkage disequilibrium with the promoter SNP, may be
      involved in the pathogenesis of chromosome 22-linked SZ.

PMID- 11317223
TI  - Evidence for association of the myo-inositol monophosphatase 2 (IMPA2) gene with
      schizophrenia in Japanese samples.
AB  - In our search for candidate genes for affective disorder on the short arm of
      chromosome 18, we cloned IMPA2, a previously unreported myo-inositol
      monophosphatase gene, that maps to 18p11.2. We determined its genomic structure
      and detected three new single nucleotide polymorphisms (SNPs). In the present
      study, we screened the gene further to search for additional polymorphisms in
      Japanese samples and identified seven other SNPs, including a novel missense
      mutation. These polymorphisms clustered into three regions of the gene. Three
      relatively informative SNPs, 58G>A, IVS1--15G>A and 800C>T from clusters 1, 2 and
      3, respectively, were selected for association tests using a case-control design.
      The Japanese cohort included 302 schizophrenics, 205 patients with affective
      disorder and 308 controls. Genotyping was done either by melting curve analysis
      on the LightCycler or by sequencing. All three SNPs showed significant genotypic
      association (nominal P = 0.031--0.0001) with schizophrenia, but not with
      affective disorder. These findings increase the relevance of 18p11.2 to
      schizophrenia susceptibility because GNAL, which has been shown previously to be
      implicated in schizophrenia in an independent study, is in close physical
      proximity to IMPA2. Our findings suggest that IMPA2 or a gene nearby may
      contribute to the overall genetic risk for schizophrenia among Japanese.

PMID- 11317224
TI  - Mutation analysis of the NMDAR2B (GRIN2B) gene in schizophrenia.
AB  - NMDA receptor dysfunction may be involved in the pathophysiology of
      schizophrenia. Based on this hypothesis, we screened 48 Japanese patients with
      schizophrenia for mutations in the coding region of the NMDAR2B subunit gene
      (GRIN2B). An association study between the identified DNA sequence variants and
      schizophrenia was performed in 268 Japanese patients with schizophrenia and 337
      Japanese control subjects. Eight single nucleotide polymorphisms were detected,
      all of which were synonymous. The association sample showed statistically
      significant excesses of homozygosity for the polymorphisms in the 3' region of
      the last exon in the patients with schizophrenia (P = 0.004) and higher frequency
      of the G allele of the 366C/G polymorphism (corrected P = 0.04) in the patients
      than in the controls. Although we did not detect NMDAR2B protein variants, our
      findings support the possibility that the GRIN2B gene or a locus in linkage
      disequilibrium with it may confer susceptibility to schizophrenia. Replication
      studies in independent samples are warranted.

PMID- 11317225
TI  - Association of a 5-HT(5A) receptor polymorphism, Pro15Ser, to schizophrenia.
AB  - Several different lines of evidence suggest that genes involved in serotonergic
      neurotransmission are factors in the pathogenesis of schizophrenia. For example,
      5-HT(5A) knockout mice revealed decreased locomotor response to lysergic
      diethylamide (LSD), which produces a psychotic-like state in healthy people.
      Recently, we reported a naturally occurring conservative Pro15Ser substitution in
      the 5-HT(5A) receptor. Here, we evaluate whether this substitution is associated
      with schizophrenia in a sample including 249 unrelated Japanese schizophrenia
      patients and 253 unrelated controls. Patients and controls were genotyped for the
      Pro15Ser polymorphism by a PCR-RFLP assay. Ser15 allele frequencies were 0.07 in
      patients with schizophrenia and 0.02 in controls (chi(2) = 17.42, df =1, P <
      0.0001). thus, we detected a highly significant association of pro15ser to
      schizophrenia in a large population of japanese schizophrenia patients and
      controls. since case-control studies have an inherent potential for false
      positive results due to population stratification, this finding is preliminary
      pending further studies, including studies using the transmission/disequilibrium
      test to eliminate stratification bias or control loci to assess ethnic matching
      of cases and controls.

PMID- 11317226
TI  - Family-based association studies of monoaminergic gene polymorphisms among North
      Indians with schizophrenia.
AB  - Associations between schizophrenia and four candidate genes were tested among
      Indian patients with schizophrenia and their parents (DSM-IV criteria, n = 179
      families). Polymorphisms within the genes encoding the serotonin 2A receptor
      (HT2A), tryptophan hydroxylase (TPH), catechol-O-methyl transferase (COMT) and
      dopamine transporter (DAT) were thus investigated. Two polymorphisms each were
      analyzed at HT2A and TPH, enabling haplotype-based analyses using the
      transmission disequilibrium test (TDT) for these genes. No significant
      associations were detected. Pooled analysis of samples like ours may be necessary
      to definitively exclude putative allelic associations at these loci.

PMID- 11317227
TI  - Association between the serotonin 2A receptor gene and tardive dyskinesia in
      chronic schizophrenia.
AB  - Tardive dyskinesia (TD) is a long-term adverse effect of antipsychotic drugs that
      are dopamine D2 receptor blockers.(1) Serotonin receptor antagonism has been
      proposed as a common mechanism contributing to the low extrapyramidal effects
      profile of atypical antipsychotic drugs.(2) We examined the association of three
      polymorphisms in the 5-HT2A receptor gene (HTR2A) with TD susceptibility-
      T102C(3) and his452tyr(4) in the coding region and A-1438G(5) in the promoter--in
      matched schizophrenia patients with (n = 59, SCZ-TD-Y) and without TD (n = 62,
      SCZ-TD-N) and normal control subjects (n = 96). The T102C and the A-1438G
      polymorphisms are in complete linkage disequilibrium but not his452tyr. There was
      a significant excess of 102C and -1438G alleles (62.7%) in the SCZ-TD-Y patients
      compared to SCZ-TD-N patients (41.1%) and controls (45.9%; chi(2) = 12.8, df = 2,
      P = 0.002; SCZ-TD-Y vs SCZ-TD-N, chi(2) = 11.4, df = 1, P = 0.0008, OR 2.41, 95%
      CI 1.43-3.99) and of 102CC and -1438GG genotypes (SCZ-TD-Y 42.4%, SCZ-TD-N,
      16.1%, controls 20.8%, chi(2) = 13.3, df = 4, P = 0.01). The 102CC and the 
      1438GG genotypes were associated with significantly higher AIMS trunk dyskinesia
      scores (F = 3.9; df = 2, 116; P = 0.02) and more incapacitation (F = 5.0; df = 2,
      115; P = 0.006). The his452tyr polymorphism showed no association with TD. These
      findings suggest that the 5-HT2A receptor gene is significantly associated with
      susceptibility to TD in patients with chronic schizophrenia. Previously reported
      association of the T102C and A-1438G polymorphisms with schizophrenia(6) may
      reflect association of a sub-group of patients with a susceptibility to abnormal
      involuntary movements related to antipsychotic drug exposure.

PMID- 11317228
TI  - Lack of association between serotonin-2A receptor gene (HTR2A) polymorphisms and
      tardive dyskinesia in schizophrenia.
AB  - Tardive dyskinesia (TD) is a disabling neurological side effect associated with
      long-term treatment with typical antipsychotics. Family studies and animal models
      lend evidence for hereditary predisposition to TD. The newer atypical
      antipsychotics pose a minimal risk for TD which is in part attributed to their
      ability to block the serotonin-2A (5-HT(2A)) receptor. 5-HT(2A) receptors were
      also identified in the basal ganglia; a brain region that plays a critical role
      in antipsychotic-induced movement disorders. We tested the significance of
      variation in the 5-HT(2A) receptor gene (HTR2A) in relation to the TD phenotype.
      Three polymorphisms in HTR2A, one silent (C102T), one that alters the amino acid
      sequence (his452tyr) and one in the promoter region (A-1437G) were investigated
      in 136 patients refractory or intolerant to treatment with typical antipsychotics
      and with a DSM-IIIR diagnosis of schizophrenia. We did not find any significant
      difference in allele, genotype or haplotype frequencies of polymorphisms in HTR2A
      among patients with or without TD (P > 0.05). Further analysis using the ANCOVA
      statistic with a continuous measure of the TD phenotype (Abnormal Involuntary
      Movement Scale (AIMS) score) found that the AIMS scores were not significantly
      influenced by HTR2A polymorphisms, despite controlling for potential confounders
      such as age, gender and ethnicity (P > 0.05). Theoretically, central serotonergic
      function can be subject to genetic control at various other mechanistic levels
      including the rate of serotonin synthesis (tryptophane hydroxylase gene),
      release, reuptake (serotonin transporter gene) and degradation (monoamine oxidase
      gene). Analyses of these other serotonergic genes are indicated. In summary,
      polymorphisms in HTR2A do not appear to influence the risk for TD. Further
      studies evaluating in tandem multiple candidate genes relevant for the
      serotonergic system are warranted to dissect the genetic basis of the complex TD
      phenotype.

PMID- 11317229
TI  - Functional polymorphism within the promotor of the serotonin transporter gene is
      associated with severe hyperkinetic disorders.
AB  - In children and adolescents, hyperkinetic disorder (HD) with conduct disorder
      (CD) and without CD and attention-deficit/hyperactivity disorder (ADHD) is known
      to be comorbid with psychiatric disorders (anxiety, depression, aggression), some
      of which are related to disturbed serotonergic neurotransmission. The efficiency
      of serotonergic signalling relates to the concentration of the neurotransmitter
      in the synaptic cleft and is controlled by the serotonin transporter (5-HTT),
      which selectively removes serotonin out of the synaptic cleft.(1)The activity of
      serotonin transport itself has been shown to be also controlled by a 5-HTT-linked
      polymorphism in its promotor region with a L/L genotype yielding higher levels of
      5-HTT function than do L/S or S/S genotypes.(2) Considering an association
      between 5-HTT polymorphism, serotonergic neurotransmission and HD +/- CD, we
      genotyped for 5-HTT polymorphism and compared patients with controls. In contrast
      to the distribution of L/L: L/S: S/S in controls (0.245: 0.509: 0.245), we found
      an enhanced expression of the L/L genotype in HD patients with CD (0.393: 0.304:
      0.304; chi(2) = 7.603; P = 0.0211) and a significant overexpression of L/L in HD
      without CD (0.542: 0.333: 0.125; chi(2) = 9.127; P = 0.0092). To our knowledge,
      this is the first finding providing evidence for an association between the 5-HTT
      polymorphism and hyperkinetic disorder, implying that serotonergic
      neurotransmission might be affected in this desease. As a consequence, for a
      successful treatment of these patients one should now also consider drugs which
      specifically modulate serotonergic signalling such as selective serotonin
      reuptake inhibitors.

PMID- 11317230
TI  - Variability in the 5-HT(2A) receptor gene is associated with seasonal pattern in
      major depression.
AB  - The 102-T/C polymorphism of the 5-HT(2A) receptor gene was analysed in 159
      patients with major depression and 164 unrelated and healthy controls using a
      case-control design. Allele and genotype frequencies did not differ between cases
      and controls. No differences according to sex, age of onset, melancholia,
      suicidal behaviour or family history of psychiatric illness were found. However,
      genotype distributions significantly differed between patients with seasonal
      pattern in their episodes (MDS) and patients with no seasonal pattern (N-MDS)
      (chi(2) = 10.63; P = 0.004). A seasonal pattern was 7.57 times more frequent in
      102C-allele carriers than in 102T homozygous (95.1% of patients MDS carried 102C
      allele vs 72% of patients N-MDS (chi(2) = 9.45, df=1, P = 0.002; OR = 7.57 (95%
      CI: 1.65--48.08)). These results suggest that variation in the 5-HT2A receptor
      gene may play a role in the development of major depression with seasonal pattern
      and support the existence of a genetic and etiological heterogeneity underlying
      the diagnosis of major depression.

PMID- 11317231
TI  - Association of anorexia nervosa with the high activity allele of the COMT gene: a
      family-based study in Israeli patients.
AB  - Anorexia nervosa (AN) is a common, severe and disabling psychiatric disorder,
      characterized by profound weight loss and body image disturbance. Family and twin
      studies indicate a significant genetic contribution and pharmacological data
      suggest possible dysfunction of the serotonergic and dopaminergic pathways.
      Catechol-O-methyltransferase (COMT) is a candidate gene for mediating
      susceptibility to AN since it is involved in the dopamine catabolism and because
      its functional polymorphism (Val/Met 158) determines high (H) and low (L)
      enzymatic activity alleles. Fifty-one Israeli AN patients and their parents were
      genotyped with the COMT polymorphism. Using the haplotype relative risk (HRR)
      method it was found that the frequency of the H allele among alleles transmitted
      to AN patients from their parents was significantly higher than in those not
      transmitted (68% vs 51% chi(2) = 5.20, df = 1, P = 0.023, odds ratio: 2.01).
      Transmission disequilibrium test (TDT) revealed that out of 49 heterozygote
      parents the H allele was transmitted to AN patients 33 times while the L allele
      was transmitted only 16 (McNemar's chi(2) = 5.90, df = 1, P = 0.015). Our study
      suggests that the COMT gene is associated with genetic susceptibility to AN, and
      that individuals homozygous for the high activity allele (HH) have a two-fold
      increased risk for development of the disorder.

PMID- 11317232
TI  - Inhibitory effects of omega-3 fatty acids on protein kinase C activity in vitro.
AB  - Preliminary clinical data indicate that omega-3 fatty acids may be effective mood
      stabilizers for patients with bipolar disorder. Both lithium and valproic acid
      are known to inhibit protein kinase C (PKC) activity after subchronic
      administration in cell culture and in vivo. The current study was undertaken to
      determine the effects of the omega-3 fatty acids eicosapentaenoic acid (EPA) and
      docosahexaenoic acid (DHA) on protein kinase C phosphotransferase activity in
      vitro. Various concentrations of DHA, EPA, and arachidonic acid (AA) were
      incubated with the catalytic domain of protein kinase C beta from rat brain.
      Protein kinase C activity was measured by quantifying incorporation of (32)P
      PO(4) into a synthetic peptide substrate. Both DHA and EPA, as well as the
      combination of DHA and EPA, inhibited PKC activity at concentrations as low as 10
      micromol l(-1). In contrast, arachidonic acid had no effect on PKC activity.
      Thus, PKC represents a potential site of action of omega-3 fatty acids in their
      effects on the treatment of bipolar disorder.

PMID- 11317237
TI  - Helicobacter pylori infection in preschool and school-aged minority children:
      effect of socioeconomic indicators and breast-feeding practices.
AB  - Helicobacter pylori infection was examined among 356 asymptomatic white Hispanic
      and black children aged 2--16 years attending 13 licensed day care centers in
      Houston. Demographic information and socioeconomic factors were evaluated. H.
      pylori status was determined by (13)C-urea breath testing. The prevalence of
      active H. pylori infection was 24% and increased with age. Prevalence was almost
      identical among white Hispanic and black children. Children living in the most
      crowded conditions were at the greatest risk for H. pylori acquisition, and an
      inverse correlation was seen between the mother's education and H. pylori
      positivity in children. Breast-feeding played a protective role against the
      acquisition of H. pylori infection. Understanding the epidemiology of H. pylori
      infection in childhood requires better understanding of the interactions between
      environment, ethnic group, and socioeconomic conditions.

PMID- 11317238
TI  - Duration of colonization by methicillin-resistant Staphylococcus aureus after
      hospital discharge and risk factors for prolonged carriage.
AB  - To investigate persistent carriage of methicillin-resistant Staphylococcus aureus
      (MRSA), we conducted a prospective 10-month study of MRSA carriage in previous
      carriers who were readmitted to our hospital. Four screening specimens, 2 from
      the skin and 2 from the nares, were obtained within 3 days after admission, in
      addition to diagnostic specimens requested by physicians. Of the 78 patients
      included in our study, 31 (40%) were persistent carriers of MRSA, with an
      estimated median time of 8.5 months to MRSA clearance. In the multivariate
      analysis, the only factor significantly associated with persistent carriage was
      the presence of a break in the skin at readmission (odds ratio, 4.34; P=.004);
      however, a trend was found for admission from a chronic-care institution (odds
      ratio, 3.65; P=.06). Our data confirm that prolonged carriage of MRSA can occur
      after hospital discharge, support routine screening for MRSA at readmission of
      previously MRSA-positive patients, and suggest that a particularly high index of
      suspicion for MRSA carriage should be maintained if these patients have a break
      in the skin.

PMID- 11317239
TI  - Inhibition of methicillin-resistant Staphylococcus aureus colonization of oral
      cavities in newborns by viridans group streptococci.
AB  - We investigated the role of viridans group streptococci in the prevention of
      colonization with methicillin-resistant Staphylococcus aureus (MRSA) in neonatal
      intensive care units. During a 26-month period at a children's hospital, 207
      (49.9%) of 415 newborns were colonized with MRSA by the time of discharge. Two
      groups of newborns with matching durations of hospitalization were compared with
      regard to the prevalence of future colonization with MRSA: group 1 (103 patients)
      did not acquire colonization with viridans group streptococci and group 2 (63
      patients) did acquire colonization with viridans group streptococci at birth or
      by 1 to 2 weeks (age, < or =11 days). The rate of colonization among patients in
      group 2 (9.5%) was significantly lower than that among patients in group 1
      (44.7%; P<.001). No significant difference in patient characteristics (e.g.,
      birth weight, diseases) was observed. These results indicate that viridans group
      streptococci, as bacteria that formerly occupied the oral cavities in newborns,
      may inhibit later colonization with MRSA.

PMID- 11317240
TI  - H(2)O(2) produced by viridans group streptococci may contribute to inhibition of
      methicillin-resistant Staphylococcus aureus colonization of oral cavities in
      newborns.
AB  - In an accompanying report, we showed that viridans group streptococci may prevent
      methicillin-resistant Staphylococcus aureus (MRSA) colonization of the oral
      cavities of newborns. In the present study, we investigated the mechanism of
      prevention in vitro. Most viridans group streptococci had bacteriocin-like
      activity and killed MRSA, Burkholderia cepacia, Enterobacter aerogenes, and
      Pseudomonas aeruginosa; however, Escherichia coli, Enterobacter cloacae, and
      Candida albicans were resistant. The activity was induced only by H(2)O(2)
      secreting strains and was inhibited by horseradish peroxidase or catalase in a
      dose-dependent manner. The mean concentration of H(2)O(2) produced by 18 strains
      of viridans group streptococci (1 x 10(8) cfu in 200 microL of culture medium+/
      standard deviation was 1.24+/-0.60 mmol. Viridans group streptococci inhibited
      MRSA growth in saliva as well as in culture media. These results indicate that
      H(2)O(2) produced by viridans group streptococci may inhibit MRSA colonization of
      oral cavities in newborns.

PMID- 11317241
TI  - A predictive model of varicella-zoster virus infection after autologous
      peripheral blood progenitor cell transplantation.
AB  - Varicella-zoster virus (VZV) frequently causes severe infections in patients who
      have undergone bone marrow transplantation. The frequency of, characteristics of,
      and risk factors for this infection were studied in 164 patients undergoing
      autologous peripheral blood progenitor cell transplantation (PBPCT). Twenty-six
      patients (15.8%) developed VZV infection, and the actuarial risk was 10% at 1
      year. No patient had visceral dissemination or died because of VZV, although one
      third of the patients developed postherpetic neuralgia. By multivariate analysis,
      a CD4(+) lymphocyte count of <200 cells/microL (P<.0001; odds ratio [OR], 2.0)
      and a CD8(+) lymphocyte count of <800 cells/microL (P=.0073; OR, 2.0) at day 30
      after transplantation were factors associated with VZV infection. Patients with
      both these adverse factors had an actuarial risk of VZV of 48% at 1 year.
      Patients with deficiency in both CD4(+) and CD8(+) lymphocytes are at high risk
      of VZV infection. These patients should be considered as candidates for
      preventive therapy, but whether for antiviral therapy or vaccination remains to
      be investigated.

PMID- 11317242
TI  - Lower respiratory tract infections due to adenovirus in hospitalized Korean
      children: epidemiology, clinical features, and prognosis.
AB  - On occasion, outbreaks of infection with adenovirus types 3, 7, and 21 cause
      severe lower respiratory tract infections (LRTIs) in children. From 1990 to 1998,
      all cases of LRTI due to adenovirus at the Seoul National University Children's
      Hospital, Seoul, Korea, were reviewed. Adenoviruses were recovered from nasal
      aspirate specimens of 87 (5.9%) of 1472 children with LRTI. The principal
      adenovirus serotypes were type 2 (13 [15%] of 87 strains), type 3 (13 [15%]), and
      type 7 (36 [41%]). Of the 87 infections, 62 (71%) occurred in children <2 years
      of age, and 81 (94%) occurred in children <5 years of age. Infections due to
      types 3 and 7 occurred during epidemics, whereas infections due to type 2
      occurred sporadically. For patients who were infected with types 3 and 7,
      extrapulmonary abnormalities were more common and homogeneous consolidation and
      pleural effusion were frequently identified on radiographs. The mortality rate
      was 12% overall and 19% among patients who were infected with type 7. Residual
      sequelae were identified in 6 (50%) of 12 patients who were infected with type 3
      and in 9 (25%) of 36 who were infected with type 7. The data confirm that
      adenovirus types 3 and 7 can cause epidemics of severe LRTI in young children.
      Epidemics of LRTIs caused by adenovirus types 3 and 7 in Korea have not been
      described in reports published elsewhere.

PMID- 11317243
TI  - Myonecrosis caused by Edwardsiella tarda: a case report and case series of
      extraintestinal E. tarda infections.
AB  - Edwardsiella tarda is an unusual human pathogen. It is primarily associated with
      gastrointestinal disease, although recent reports of extraintestinal disease are
      broadening the current understanding of the clinical spectrum of E. tarda. A
      series of 11 cases of extraintestinal E. tarda infection is presented, including
      the first reported case of myonecrosis in an immunocompetent patient. Wound
      infections were the most common manifestation, and 3 of 5 patients with infected
      wounds had been exposed to a marine environment. One patient had bacteremia, and
      the remaining 5 patients developed abscesses that required surgical drainage.
      Four patients had E. tarda isolated in pure culture, including the patient with
      myonecrosis. Although it is often difficult to ascertain the contribution of E.
      tarda to infection when it is isolated as part of a mixed culture, this case
      series suggests that E. tarda is singularly capable of causing limb- and life
      threatening infections.

PMID- 11317244
TI  - Tickborne infections as a cause of nonspecific febrile illness in Wisconsin.
AB  - Lyme disease, human granulocytic ehrlichiosis (HGE), and babesiosis are tickborne
      infections that are indigenous to Wisconsin. To assess their importance as a
      cause of nonspecific fever, we recruited patients with febrile illness at 10
      clinics in northwestern Wisconsin from May through August of both 1997 and 1998.
      Eligible patients had a temperature >38.0 degrees C but no rash or other
      localizing source. Acute and convalescent serological tests were performed for
      Borrelia burgdorferi, Babesia microti, and Ehrlichia equi; polymerase chain
      reaction was performed to detect granulocytic Ehrlichia rDNA. Seventeen (27%) of
      62 eligible patients had laboratory evidence of tickborne infection, including 7
      (11%) with probable Lyme disease only, 8 (13%) with HGE only, and 2 (3%) with
      apparent coinfection. No patients with Babesia infection were identified.
      Patients with and without tickborne infection were similar with regard to age,
      sex, symptoms, history of tick bite, and outdoor exposure. The results suggest
      that tickborne infections are an important cause of nonspecific febrile illness
      during the tick season in northwestern Wisconsin.

PMID- 11317245
TI  - Myocarditis, a rare but severe manifestation of Q fever: report of 8 cases and
      review of the literature.
AB  - Myocarditis has only rarely been described as a manifestation of acute Q fever.
      Among our series of 1276 patients in whom acute Q fever was diagnosed during 1985
      -1999, myocarditis was diagnosed in 8. Two patients (25.0%) developed cardiac
      symptoms during the course of interstitial pneumonia, 2 (25.0%) initially
      presented with unexplained fever, and 1 (12.5%) presented with febrile cutaneous
      rash. In 3 patients, cardiac symptoms were inaugural: 1 patient experienced heart
      failure, and 2 experienced precordial pain. Dilated cardiomyopathy was documented
      in 7 patients, and 2 (1 of whom had undergone heart transplantation) died despite
      therapy. In addition, 1 patient was scheduled for heart transplantation because
      of cardiac insufficiency. When the patients in this study were compared with 32
      control patients with acute Q fever, no specific epidemiological or clinical
      features were associated with this disease except worse prognosis (P=.006).
      Moreover, among the 12 patients from our series who died as a result of acute Q
      fever, 2 patients, who were significantly younger than the other 9 patients
      (P=.03), had myocarditis. Our study highlights the severity of Coxiella burnetii
      myocarditis.

PMID- 11317246
TI  - Gastrointestinal basidiobolomycosis in Arizona: clinical and epidemiological
      characteristics and review of the literature.
AB  - Gastrointestinal basidiobolomycosis (GIB) is an unusual fungal infection that is
      rarely reported in the medical literature. From April 1994 through May 1999, 7
      cases of GIB occurred in Arizona, 4 from December 1998 through May 1999. We
      reviewed the clinical characteristics of the patients and conducted a case
      control study to generate hypotheses about potential risk factors. All patients
      had histopathologic signs characteristic of basidiobolomycosis. Five patients
      were male (median age, 52 years; range, 37--59 years) and had a history of
      diabetes mellitus (in 3 patients), peptic ulcer disease (in 2), or pica (in 1).
      All patients underwent partial or complete surgical resection of the infected
      portions of their gastrointestinal tracts, and all received itraconazole
      postoperatively for a median of 10 months (range, 3--19 months). Potential risk
      factors included prior ranitidine use and longer residence in Arizona. GIB is a
      newly emerging infection that causes substantial morbidity and diagnostic
      confusion. Further studies are needed to better define its risk factors and
      treatment.

PMID- 11317247
TI  - Bacillus cereus bacteremia and meningitis in immunocompromised children.
AB  - Two cases of Bacillus cereus meningitis in immunocompromised children at our
      hospital within a 2-month period prompted us to review B. cereus--related
      invasive disease. We identified 12 patients with B. cereus isolated in blood
      cultures from September 1988 through August 2000 at our institution. Three of
      these patients also had B. cereus isolated from CSF specimens; 1 additional
      patient had possible CNS involvement (33%, group A), whereas 8 patients had no
      evidence of CNS involvement (67%, group B). Patients in group A were more likely
      to have neutropenia at the onset of sepsis and were more likely to have an
      unfavorable outcome. They were also more likely to have received intrathecal
      chemotherapy in the week before the onset of their illness. Two patients from
      group A died. One survived with severe sequelae. The fourth patient had mild
      sequelae at follow-up. No sequelae or deaths occurred among patients in group B.
      In patients with unfavorable outcomes, the interval from the time of recognition
      of illness to irreversible damage or death was short, which demonstrates a need
      for increased awareness, early diagnosis, and more-effective therapy,
      particularly that which addresses B. cereus toxins.

PMID- 11317248
TI  - Carriage of antibiotic-resistant pneumococci among Asian children: a
      multinational surveillance by the Asian Network for Surveillance of Resistant
      Pathogens (ANSORP).
AB  - To investigate the nasal carriage of antibiotic-resistant pneumococci by
      children, anterior nasal swabs were done for 4963 children <5 years old in 11
      countries in Asia and the Middle East. In total, 1105 pneumococci isolates
      (carriage rate, 22.3%) were collected, 35.8% of which were found to be
      nonsusceptible to penicillin. Prevalence of penicillin nonsusceptibility was
      highest in Taiwan (91.3%), followed by Korea (85.8%), Sri Lanka (76.5%), and
      Vietnam (70.4%). Penicillin resistance was related to residence in urban areas,
      enrollment in day care, and a history of otitis media. The most common serogroups
      were 6 (21.5%), 23 (16.5%), and 19 (15.7%). The most common clone, as assessed by
      pulsed-field gel electrophoresis, was identical to the Spanish 23F clone and to
      strains of invasive isolates from adult patients. Data in this study documented
      the high rate of penicillin or multidrug resistance among isolates of pneumococci
      carried nasally in children in Asia and the Middle East and showed that this is
      due to the spread of a few predominant clones in the region.

PMID- 11317249
TI  - Recurrent nonmenstrual toxic shock syndrome: clinical manifestations, diagnosis,
      and treatment.
AB  - We report 3 cases of recurrent nonmenstrual toxic shock syndrome (TSS) and review
      the clinical manifestations, diagnosis, and treatment. The primary sites of
      infection were the genital tract (in a patient who underwent cesarean delivery),
      the upper respiratory tract, and a breast abscess. In all 3 patients, the initial
      illness was not recognized to be TSS; only after development of recurrent illness
      with desquamation was this diagnosis entertained. Strains of Staphylococcus
      aureus that were isolated from 2 patients produced TSS toxin-1, whereas the third
      strain produced staphylococcal enterotoxin B. All 3 patients lacked antibody to
      the implicated toxins at the time of presentation with recurrent illness.
      Nonmenstrual TSS can occur in a variety of clinical settings and may be
      recurrent. The presence of desquamation during a febrile, multisystem illness
      could suggest this diagnosis and should prompt the clinician to obtain
      appropriate cultures for S. aureus.

PMID- 11317250
TI  - Herpes zoster in older adults.
AB  - Herpes zoster (HZ) strikes millions of older adults annually worldwide and
      disables a substantial number of them via postherpetic neuralgia (PHN). Key age
      related clinical, epidemiological, and treatment features of zoster and PHN are
      reviewed. HZ is caused by renewed replication and spread of varicella-zoster
      virus (VZV) in sensory ganglia and afferent peripheral nerves in the setting of
      age-related, disease-related, and drug-related decline in cellular immunity to
      VZV. VZV-induced neuronal destruction and inflammation causes the principal
      problems of pain, interference with activities of daily living, and reduced
      quality of life in elderly patients. Recently, attempts to reduce or eliminate HZ
      pain have been bolstered by the findings of clinical trials that antiviral agents
      and corticosteroids are effective treatment for HZ and that tricyclic
      antidepressants, topical lidocaine, gabapentin, and opiates are effective
      treatment for PHN. Although these advances have helped, PHN remains a difficult
      condition to prevent and treat in many elderly patients.

PMID- 11317251
TI  - Changing spectrum of mortality due to human immunodeficiency virus: analysis of
      260 deaths during 1995--1999.
AB  - We analyzed the deaths in an outpatient human immunodeficiency virus (HIV) care
      clinic at University Hospitals in Cleveland from January 1995 through December
      1999. The number of annual deaths decreased progressively, from 112 in 1995 to 32
      in 1999. The median final CD4(+) cell count before death increased progressively
      from 10 cells/microL in 1995 to 90 cells/microL in 1999 (P<.01); 20%--25% of
      patients who died from 1997 through 1999 had plasma HIV RNA levels below
      detection limits. From 1995 through 1998, deaths due to infection, to end-stage
      acquired immune deficiency syndrome, and to malignancies decreased, whereas the
      proportion of deaths due to end-organ failures and of uncertain relationship to
      HIV infection increased. The spectrum of mortality in HIV disease has changed
      recently; although opportunistic infections cause death less frequently, deaths
      are occurring in people who have control of HIV replication and with some
      preservation of immune function. These observations underscore the need to
      monitor the etiologies of HIV-associated mortality and to better our
      understanding of the relationships among immune defenses, treatment-related
      toxicities, and end-organ failure in patients with HIV disease.

PMID- 11317252
TI  - Tolerability of postexposure prophylaxis with zidovudine, lamivudine, and
      nelfinavir for human immunodeficiency virus infection.
AB  - Tolerability of the combination of zidovudine, lamivudine, and nelfinavir used as
      postexposure prophylaxis (PEP) for HIV infection was prospectively evaluated
      among 185 patients at 11 hospitals in eastern France. After exclusion of the 106
      persons who discontinued PEP either because the source patient subsequently
      tested HIV seronegative or because the injury was reassessed as resulting in a
      low risk for transmission of HIV, 67 (85%) of the patients who received such PEP
      experienced adverse effects, which led to withdrawal of nelfinavir in 28 (35%) of
      these patients.

PMID- 11317253
TI  - Iron status and indicators of human immunodeficiency virus disease severity among
      pregnant women in Malawi.
AB  - The relationships among hemoglobin, ferritin, and transferrin receptor levels and
      2 markers of human immunodeficiency virus (HIV) disease severity--HIV load and
      CD4(+) lymphocyte count--were characterized among 483 pregnant women in Malawi,
      Africa. The only significant correlation was an inverse correlation between
      hemoglobin level and plasma HIV load (r=-.104; P<.03). The prevalence of iron
      deficiency anemia was not significantly different across quartiles of HIV load or
      CD4(+) lymphocyte count. In contrast to previous studies, these data suggest that
      iron status is not related to markers of HIV disease severity in pregnant women
      in Africa.

PMID- 11317254
TI  - Detection of human herpesvirus-8 DNA in kidney allografts prior to the
      development of Kaposi's sarcoma.
AB  - Human herpesvirus-8 (HHV-8) DNA was identified in kidney allografts in 2 of 3
      transplant recipients prior to the development of Kaposi's sarcoma, and increase
      in viral antibody titer was found in the third. Combined genotypic and serologic
      analyses could be used to identify patients at risk and suggest that the kidney
      may be a site of HHV-8 latency.

PMID- 11317255
TI  - Vertebral osteomyelitis due to infection with nontuberculous Mycobacterium
      species after blunt trauma to the back: 3 examples of the principle of locus
      minoris resistentiae.
AB  - Osteomyelitis due to infection with nontuberculous mycobacterial organisms is
      unusual, especially in the absence of nonpenetrating trauma. We describe 3
      patients with vertebral osteomyelitis due to infection with nontuberculous
      mycobacterial organisms that was precipitated by blunt trauma; these 3 unusual
      cases illustrate the principle of locus minoris resistentiae.

PMID- 11317256
TI  - Streptococcus intermedius, Streptococcus constellatus, and Streptococcus
      anginosus ("Streptococcus milleri group") are of different clinical importance
      and are not equally associated with abscess.
AB  - Difficulties in distinguishing organisms of the "Streptococcus milleri group"
      (SMG; Streptococcus intermedius, Streptococcus constellatus, and Streptococcus
      anginosus), have caused ambiguity in determining their pathogenic potential. We
      reviewed 118 cases in which SMG isolates had been identified using 16S rDNA
      sequence. S. constellatus and S. anginosus were isolated far more frequently than
      was S. intermedius. Nearly all isolates of S. intermedius and most isolates of S.
      constellatus, but only 19% of those of S. anginosus, were associated with
      abscess. Our findings suggest that speciation of the SMG may guide diagnostic
      evaluation, give insight into the possible role of coinfecting organisms, and
      help assess the need to search for occult abscess.

PMID- 11317257
TI  - Paromomycin in cryptosporidiosis.

PMID- 11317258
TI  - Testing of urinary Escherichia coli isolates for Shiga toxin production.

PMID- 11317260
TI  - Treatment of foodborne listeriosis.

PMID- 11317261
TI  - Sir Thomas Sydenham revisited.

PMID- 11317263
TI  - Elimination of efficacy by additives in zinc acetate lozenges for common colds.

PMID- 11317264
TI  - Novel presentation and approach to management of hepatopulmonary syndrome with
      use of antimicrobial agents.
AB  - A 44-year-old man with hepatitis C-associated liver cirrhosis, cyanosis, digital
      clubbing, and platypnea presented with left-side hemiplegia found to be due to a
      brain abscess. Hepatopulmonary syndrome was diagnosed after demonstration of the
      presence of a massive intrapulmonary shunt. Although the anomalous vascular
      channel never was defined anatomically, follow-up studies confirmed the presence
      of a functional shunt. Culture of a sample from the abscess yielded Streptococcus
      intermedius. It was hypothesized that the patient's pulmonary vascular pathology
      was due, in large part, to chronic elevated levels of nitric oxide (a potent
      vasodilator thought to be generated by endotoxin absorbed from the gut).
      Treatment with oral norfloxacin was initiated on the basis of data that this
      antibiotic reduces endotoxemia and concomitant nitric oxide production in
      patients with cirrhosis. Four months after initiation of treatment, the patient's
      hypoxia had resolved.

PMID- 11317265
TI  - Successful treatment of aspergillus brain abscess with itraconazole and
      interferon-gamma in a patient with chronic granulomatous disease.
AB  - This report describes the successful treatment of Aspergillus brain abscess in a
      boy with chronic granulomatous disease.

PMID- 11317266
TI  - Abiotrophia bacteremia in a patient with neutropenic fever and antimicrobial
      susceptibility testing of Abiotrophia isolates.
AB  - We report a case of bacteremia due to Abiotrophia species in a patient with
      neutropenic fever and cancer who was receiving levofloxacin prophylaxis, followed
      by empirical therapy with cefepime; the organism was resistant to both
      antibiotics. We provide susceptibility data on 20 additional bloodstream isolates
      of Abiotrophia species.

PMID- 11317267
TI  - Isolated presence of antibody to hepatitis B core antigen in injection drug
      users: do they need to be vaccinated?
AB  - In a study of 497 injection drug users who had isolated presence of antibody to
      hepatitis B core antigen (anti-HBc) at the time of enrollment, 404 (81%) retained
      this condition after a mean of 49 months of follow-up, during which time no new
      hepatitis B surface antigen marker was detected. These findings support the
      hypothesis that patients with isolated presence of anti-HBc have strong
      resistance to reinfection and do not need vaccination.

PMID- 11317268
TI  - Molecular mechanisms of neurotransmitter release.
AB  - The release of neurotransmitter from neurons represents one of the pivotal events
      in synaptic transmission. Neurotransmitters are released from synaptic vesicles
      in presynaptic neurons in response to neural activity, diffuse across the
      synaptic cleft, and bind specific receptors in order to bring about changes in
      postsynaptic neurons. Some of the molecular processes that govern
      neurotransmitter release are now becoming better understood. The steps involved
      can be broken down into two partially overlapping presynaptic cycles, the
      neurotransmitter cycle and the synaptic vesicle cycle. The neurotransmitter cycle
      involves transmitter biosynthesis, storage, reuptake, and degradation. The
      synaptic vesicle cycle involves targeting to the nerve terminal, docking, fusion,
      endocytosis, and recycling. Biochemical and structural studies have yielded
      important insight into our understanding of each of these two cycles. Further,
      both pharmacological and genetic interference with either of these cycles results
      in profound alterations in synaptic transmission and behavior, demonstrating the
      crucial role of neurotransmitter release.

PMID- 11317269
TI  - Mechanisms underlying human motor system plasticity.
AB  - There has been increased interest in the ability of the adult human nervous
      system to reorganize and adapt to environmental changes throughout life. This
      ability has been termed "plasticity." Plastic changes in the cerebral cortex have
      been studied: (a) as modifications of sensory or motor cortical representation of
      specific body parts (cortical maps, body representation level); and (b) as
      changes in the efficacy of existing synapses or generation of new synapses
      (neuronal or synaptic level). In this review, we describe paradigms used to study
      mechanisms of plasticity in the intact human motor system, the functional
      relevance of such plasticity, and possible ways to modulate it.

PMID- 11317270
TI  - Informed consent.
AB  - Physicians have an ethical and legal duty to obtain patients' informed consent
      before ordering testing and treatment. Informed consent encompasses informed
      refusal, the correlative right of patients to refuse tests and therapies they do
      not want. A patient's informed consent requires adequate information, capacity to
      decide, and absence of coercion. Informed consent is incorporated into a process
      of agreement between a patient and a physician called "shared decision making."
      The procedural requirements of informed consent vary as a function of the risks
      of the tests or treatments. Incompetent patients require surrogate decision
      makers to consent or refuse on their behalf. Older children and adolescents
      should be asked to provide their assent for treatment in addition to their
      parents' permission. Treatment may be provided in an emergency situation without
      consent if the treatment given represents the standard of emergency care. Consent
      of human subjects for participation in research requires that they fully
      understand their role and risks, not be coerced, and be allowed to withdraw at
      any time without penalty. Institutional review boards help guarantee the
      protection of human subjects. Vulnerable research subjects, such as children and
      the cognitively or mentally impaired, require additional protection.

PMID- 11317271
TI  - Insulin treatment enhances expression of IGF-I in sural nerves of diabetic
      patients.
AB  - We studied the expression of insulin-like growth factor I (IGF-I) and its
      receptor in sural nerves from 8 diabetic patients divided into insulin-treated
      (IT) and non-insulin-treated (NIT) groups, compared with 5 patients with axonal
      neuropathies and 4 control patients (undergoing biopsies for diagnostic
      purposes). Insulin-like growth factor I mRNA levels did not differ in diabetic
      cases compared with control subjects. In sural nerves from IT patients and axonal
      neuropathies, IGF-I expression was higher than in NIT subjects and diagnostic
      controls. Changes in IGF-I receptor mRNA levels paralleled those of the ligand.
      Insulin-like growth factor I immunoreactivity was higher in nerves undergoing
      axonal degeneration and higher in IT than NIT diabetic patients and diagnostic
      controls. These findings suggest that insulin treatment increases IGF-I
      expression in diabetic nerves. Our data do not support the hypothesis of an
      absolute IGF-I deficiency in human diabetic neuropathy. A Schwann cell's
      incapacity to increase IGF-I expression after severe nerve damage, as happens in
      axonal neuropathies, may be a cofactor in the pathogenesis of diabetic
      neuropathy.

PMID- 11317272
TI  - Familial continuous motor unit activity and epilepsy.
AB  - A mother and son both had muscle stiffness due to continuous generalized muscle
      twitching, beginning in childhood and associated with epileptic seizures.
      Electromyography (EMG) showed continuous motor unit activity (CMUA) at rest,
      which decreased during ischemia, sleep, and carbamazepine treatment, and was
      abolished by anesthetic nerve blockade. Genetic analysis disclosed a G724C point
      mutation in the potassium channel KCNA1 gene. The electrophysiological data
      suggested pathological impulse generation in both the peripheral and central
      nervous system, probably related to abnormal ion channel function.

PMID- 11317273
TI  - Lidocaine selectively blocks abnormal impulses arising from noninactivating Na
      channels.
AB  - Abnormal, repetitive impulse firing arising from incomplete inactivation of Na+
      channels may be involved in several diseases of muscle and nerve, including
      familial myotonias and neuropathic pain syndromes. Systemic local anesthetics
      have been shown to have clinical efficacy against myotonias and some forms of
      neuropathic pain, so we sought to develop an in vitro model to examine the
      cellular basis for these drugs' effects. In frog sciatic nerves, studied in vitro
      by the sucrose-gap method, peptide alpha-toxins from sea anemone (ATXII) or
      scorpion (LQIIa) venom, which inhibit Na+ channel inactivation, induced
      repetitively firing compound action potentials (CAPs) superimposed on a plateau
      depolarization lasting several seconds. The initial spike of the CAP was
      unaffected, but the plateau and repetitive firing were strongly suppressed by 5
      30 microM lidocaine. Lidocaine caused a rapid, concentration-dependent decay of
      the plateau, quantitatively consistent with blockade of open Na(+) channels.
      Early and late repetitive firing were equally suppressed by lidocaine with IC50 =
      10 microM. After washout of lidocaine and LQIIa, the plateau and repetitive
      firing remained for > 1 h, showing that lidocaine had not caused dissociation of
      channel-bound alpha-toxin. These findings indicate that therapeutic
      concentrations of lidocaine can reverse the "abnormal" features of action
      potentials caused by non-inactivating Na+ channels without affecting the normal
      spike component.

PMID- 11317274
TI  - Subcutaneous microdialysis in mitochondrial cytopathy.
AB  - We present the results of subcutaneous microdialysis, a new minimally invasive
      biochemical monitoring technique, in mitochondrial cytopathy. We studied 6
      ambulatory patients with mitochondrial cytopathy and 6 controls without
      mitochondrial disease using a subcutaneous probe for continuous microdialysis,
      and obtained measurements of lactate, pyruvate, and glucose from samples gathered
      at 30-60 min intervals during the day and at 3-h intervals at night. The
      lactate:pyruvate ratio (LPR) was calculated and related to disease severity and
      metabolic stress. Microdialysis was well tolerated. Controls had stable lactate
      and pyruvate values in the normal range and a low LPR (average values between
      0.0114 and 0.0145). Patients had widely fluctuating lactate and pyruvate values,
      a higher average LPR between 0.0187 and 0.0724, and marked diurnal variation,
      especially in the severely affected patients. Increases in the LPR coincided with
      metabolic stress in individual cases. We conclude that subcutaneous microdialysis
      is well tolerated and enables continuous metabolic monitoring of patients with
      mitochondrial cytopathy. It has particular potential for use in the
      identification of metabolic risk factors and may help to assess the impact of
      therapeutic regimens.

PMID- 11317275
TI  - Muscle metabolic economy is inversely related to exercise intensity and type II
      myofiber distribution.
AB  - It is not known what causes the well-established inverse relationship between
      whole-body exercise economy and exercise intensity. The purpose of this study was
      to: (1) evaluate muscle exercise economy at 45%, 70%, and maximum isometric
      strength using 31P magnetic resonance spectroscopy (31P-MRS); and (2) determine
      the relationship between percent type II muscle fiber cross-section, whole-body
      exercise economy, and muscle exercise economy. Subjects included 32 premenopausal
      women. Muscle exercise economy was significantly different across the three
      exercise intensities (28.1 +/- 10.4, 24.8 +/- 8.2, and 20.2 +/- 7.5 N/cm2. mmol/L
      adenosine triphosphate [ATP] for the 45%, 70%, and maximum intensities,
      respectively). Percent type II muscle area was significantly related to whole
      body metabolic economy during activities of daily living (r = -0.68) and 31P-MRS
      muscle metabolic economy during isometric plantar flexion (r = -0.53). These data
      suggest that skeletal muscle becomes less economical as force production
      increases, and that these decreases in metabolic economy may be related to
      increased dependence on inefficient type II muscle.

PMID- 11317276
TI  - Partial peripheral motor nerve lesions induce changes in the conduction
      properties of remaining intact motoneurons.
AB  - A partial injury or loss of peripheral motor axons is followed by compensatory
      sprouting of remaining intact motor axons in order to reinnervate muscle. Little
      is known, however, about the electrophysiologic properties proximally of these
      intact motoneurons and their axons following injury of neighboring motor axons.
      We studied the conduction properties of intact cat motor axons and motoneurons
      proximal to the site of a partial peripheral nerve section. Twelve weeks after
      the partial transection of the cat medial gastrocnemius motor nerve, there was a
      significant (7%) reduction in conduction velocity and a 13% prolongation in
      afterhyperpolarization half-decay time in the remaining intact motoneurons,
      compared with controls. Partial injury to motor nerves thus induces reactive
      electrophysiologic changes in the remaining intact motoneurons and their axons,
      perhaps associated with compensatory sprouting within partially denervated
      muscle.

PMID- 11317277
TI  - Physiological alterations of maximal voluntary quadriceps activation by changes
      of knee joint angle.
AB  - The purpose of this study was to investigate the influence of different angles of
      the knee joint on voluntary activation of the quadriceps muscle, estimating the
      ability of a subject to activate a muscle maximally by means of voluntary
      contraction. Isometric torque measurement was performed on 6 healthy subjects in
      5 degrees intervals between 30 degrees and 90 degrees of knee joint flexion.
      Superimposed twitches at maximal voluntary contraction (MVC) and at a level of
      60% and 40% of the MVC were applied and the voluntary activation estimated. At
      between 30 degrees and 75 degrees of knee flexion, the maximal extension torque
      increased at an average rate of 2.67 +/- 0.6 Nm/degree, followed by a decline
      with further flexion. However, throughout the joint-angle range tested, voluntary
      activation increased on average by 0.37%/degree with a maximum at 90 degrees of
      flexion. Due to the influence of joint position it is not possible to generalize
      results obtained at the knee joint angle of 90 degrees of flexion, which is
      usually used for the quadriceps twitch-interpolation technique. Consequently, it
      is useful to investigate voluntary activation deficits in knee joint disorders at
      a range of knee joint angles that includes, in particular, the more extended
      joint angles used frequently during daily activity.

PMID- 11317278
TI  - Impairment of voluntary control of finger motion following stroke: role of
      inappropriate muscle coactivation.
AB  - Subjects with chronic hemiplegia following stroke attempted to perform voluntary
      isometric, isokinetic, and free contractions of the extensor muscles of the
      metacarpophalangeal (MCP) joints. We recorded torque, metacarpophalangeal joint
      angle and velocity, and electromyographic (EMG) activity of the extrinsic
      extensors and flexors and the first dorsal interosseous (FDI). We found that
      voluntary MCP joint extension in hemiparetic subjects was greatly impaired in
      comparison with control subjects: only two of the 11 stroke subjects were able to
      generate even 0.21 N-m of isometric extension torque, only two could produce
      positive finger extension with no load, and none could develop an isokinetic
      concentric extension. Deficits seemed to result from a combination of
      coactivation of the finger flexor and extensor muscles and decreased voluntary
      excitation of the extensors, as normalized flexor and FDI EMG activity were
      greater for stroke than for control subjects (P < 0.001), but normalized extensor
      activity was reduced (P < 0.001).

PMID- 11317279
TI  - Creatine transporter and mitochondrial creatine kinase protein content in
      myopathies.
AB  - Total creatine or phosphocreatine, or both, are reduced in the skeletal muscle of
      patients with inflammatory myopathy, mitochondrial myopathy, and muscular
      dystrophy/congenital myopathy. We used Western blotting techniques to measure
      skeletal muscle creatine transporter protein and sarcomeric mitochondrial
      creatine kinase (mtCK) protein content in patients with inflammatory myopathy (N
      = 8), mitochondrial myopathy (N = 5), muscular dystrophy (N = 7), and congenital
      myopathy (N = 3), as compared to a control group without a neuromuscular
      diagnosis (N = 8). Creatine transporter protein content was lower for all groups
      compared to control subjects (P < 0.05; P < 0.01 for congenital myopathy).
      Mitochondrial CK (mtCK) was lower for inflammatory myopathy (P < 0.05), higher
      for mitochondrial myopathy (P < 0.05), not different for muscular dystrophy, and
      markedly lower for the congenital myopathy group (P < 0.01), compared to control
      subjects. Together, these data suggest that the reduction in total creatine or
      phosphocreatine in patients with certain myopathies is correlated with creatine
      transporter and not mtCK protein content. This further supports the belief that
      creatine monohydrate supplementation may benefit patients with low muscle
      creatine stores, although the reduction in creatine transporter protein may have
      implications for dosing.

PMID- 11317280
TI  - Distal sensory nerve conduction of the superficial peroneal nerve: new method and
      its clinical application.
AB  - The superficial peroneal nerve subserves sensation on the entire surface of the
      dorsum of the foot, except in small areas. All previously reported techniques for
      evaluating nerve conduction along this nerve tested a proximal portion of the
      nerve. We report a new method for evaluating sensory nerve conduction of the four
      branches of the distal superficial peroneal nerve. Two branches to the second and
      third toes of the medial dorsal cutaneous nerve and two branches to the fourth
      and fifth toes of the intermediate dorsal cutaneous nerve were studied
      orthodromically and antidromically in 37 feet of 21 normal volunteers using
      surface stimulating and recording electrodes and with a distance of 10 cm between
      the stimulating and recording electrodes. Maximum nerve conduction velocities
      (NCV) ranged from 41.8 to 46.9 m/s, and mean response amplitude ranged from 6.5
      to 7.6 microV with the orthodromic technique. Values for NCV were almost
      identical when elicited by antidromic and orthodromic techniques, but response
      amplitudes were higher with the antidromic technique. Mean amplitudes of the
      distal superficial peroneal nerve were about 50% of the proximal superficial
      peroneal, and the conduction velocity in the distal superficial peroneal was
      slower than that in the proximal superficial peroneal nerve, by 8-14 m/s. In
      seven cases, distal superficial peroneal neuropathy was confirmed with this
      technique: two with proper digital neuropathy, two with medial dorsal cutaneous
      neuropathy, and three with intermediate dorsal cutaneous neuropathy.

PMID- 11317281
TI  - Leukemia inhibitory factor enhances regeneration in skeletal muscles after
      myoblast transplantation.
AB  - Cell-based therapies, such as myoblast transfer therapy, are likely to become an
      integral part of any approach to treat myopathies such as Duchenne muscular
      dystrophy. Previous studies have shown that an increased level of regeneration in
      the host muscle enhances incorporation of donor myoblasts. Leukemia inhibitory
      factor (LIF) increases the number of dystrophic fibers expressing dystrophin
      after myoblast transplantation and enhances regeneration in injured and diseased
      muscle. Morphometric analysis was used to investigate whether an increased level
      of regeneration is induced by LIF after myoblast transplantation. We found that,
      in muscles treated with LIF, the number of fibers undergoing regeneration was
      increased. The increased incorporation of donor myoblasts and thus dystrophin
      expression induced by LIF may be due, at least in part, to an increased level of
      regeneration of dystrophic muscle.

PMID- 11317282
TI  - Localization of ulnar neuropathy with conduction block across the elbow.
AB  - We performed short segment incremental stimulation on 13 consecutive patients
      with ulnar neuropathy across the elbow (UNE) and conduction block. Conduction
      block occurred proximal to the medial epicondyle in 62%, at the epicondyle in
      23%, and below the elbow in 15%. The ulnar nerve may be more prone to external
      compression above the elbow than previously recognized. Short segment incremental
      studies are useful to identify conduction block above the elbow in such patients.

PMID- 11317283
TI  - Parameters for monitoring treatment effects in CIDP with anti-MAG/SGPG IgM
      antibody.
AB  - We used cycles of plasma exchange and intravenous cyclophosphamide to treat a
      patient who had chronic inflammatory demyelinating polyneuropathy with anti
      myelin-associated glycoprotein/sulfoglucuronylparagloboside IgM antibody. After
      treatment, serum anti-sulfoglucuronylparagloboside IgM antibody titers were
      reduced significantly, and clear symptomatic improvement followed. The percentage
      of CD57-positive lymphocytes and natural killer cell activity had also returned
      to normal. Our findings indicate that serial measurements of these parameters are
      useful for monitoring treatment effect in this disease.

PMID- 11317286
TI  - Factors Controlling the Addition of Carbon-Centered Radicals to Alkenes-An
      Experimental and Theoretical Perspective.
AB  - The successful exploitation of syntheses involving the generation of new carbon
      carbon bonds by radical reactions rests on some prior knowledge of the rate
      constants for the addition of carbon-centered radicals to alkenes and other
      unsaturated molecules, and of the factors controlling them. Two former classical
      reviews in Angewandte Chemie by Tedder (1982) and by Giese (1983) provided
      mechanistic insight and led to various qualitative rules on the complex interplay
      of enthalpic, polar, and steric effects. In the meantime, the field has
      experienced very rapid progress: many more experimental absolute rate constants
      have become available, and there have been major advances in the efficiency and
      reliability of quantum-chemical methods for the accurate calculation of
      transition structures, reaction barriers, and reaction enthalpies. Herein we
      review this progress, recommend suitable experimental and theoretical procedures,
      and display representative data series for radical additions to alkenes. On this
      basis, and guided by the pictorial tool of the state-correlation diagram for
      radical additions, we then offer a new and more stringent quantification of the
      controlling factors. Our analysis leads to a partial revision of the previous
      qualitative rules, and it more clearly exhibits the interplay of the reaction
      enthalpy effects, polar charge-transfer contributions, and steric substituent
      effects on the reaction energy barrier. The various contributions are cast into
      the form of new, simple, and physically meaningful but non-linear, predictive
      equations for the preestimation of rate constants. These equations prove
      successful in several tests but call for additional theoretical and experimental
      foundation. The kinetics of related reactions such as polymer propagation,
      copolymerization, and the addition of radicals to alkynes and aromatic compounds
      is shown to follow the same principles.

PMID- 11317288
TI  - Wittig and His Accomplishments: Still Relevant Beyond His 100th Birthday A
      condensed version of a lecture given on the occasion of the inauguration of the
      Georg Wittig Lectureship at the Universitat Heidelberg (27.10.1999).

PMID- 11317287
TI  - New Concepts in Tetrathiafulvalene Chemistry.
AB  - Tetrathiafulvalene (TTF) and its derivatives were originally prepared as strong
      electron-donor molecules for the development of electrically conducting
      materials. This Review emphasizes how TTF and its derivatives offer new and in
      some cases little-exploited possibilities at the molecular to the supramolecular
      levels, as well as in macromolecular aspects. TTF is a well-established molecule
      whose interest goes beyond the field of materials chemistry to be considered an
      important building block in supramolecular chemistry, crystal engineering, and in
      systems able to operate as machines. At the molecular level, TTF is a readily
      available molecule which displays a strong electron-donor ability. However, its
      use as a catalyst for radical-polar crossover reactions, thus mimicking samarium
      iodide chemistry, has only recently been addressed. Important goals have been
      achieved in the use of TTF at the macromolecular level where TTF-containing
      oligomers, polymers, and dendrimers have allowed the preparation of new materials
      that integrate the unique properties of TTF with the processability and stability
      that macromolecules display. The TTF molecule has also been successfully used in
      the construction of redox-active supramolecular systems. Thus, chemical sensors
      and redox-switchable ligands have been prepared from TTF while molecular shuttles
      and molecular switches have been prepared from TTF-containing rotaxanes and
      catenanes. A large synthetic effort has been devoted to the preparation of the so
      called organic ferromagnets, many of which are derived from TTF. The main task in
      these systems is the introduction of ferromagnetic coupling between the
      conduction electrons and localized electrons. TTF has also played a prominent
      role in molecular electronics where TTF-containing D-sigma-A molecules have
      allowed the preparation of the first confirmed unimolecular rectifier. Recently,
      it has been confirmed that TTF can display efficient nonlinear optic (NLO)
      responses in the second and third harmonic generation as well as a good thermal
      stability. These findings can be combined with the redox ability of TTF as an
      external stimuli to provide a promising strategy for the molecular engineering of
      switchable NLO materials. Fullerenes endowed with TTF exhibit outstanding
      photophysical properties leading to charge-separated (CS) states that show
      remarkable lifetimes.

PMID- 11317289
TI  - Inorganic Chemistry in Marine Sediments.

PMID- 11317290
TI  - A Renaissance in Noble Gas Chemistry.

PMID- 11317291
TI  - [{Fe]

PMID- 11317292
TI  - High-Density Labeling of DNA: Preparation and Characterization of the Target
      Material for Single-Molecule Sequencing The authors are grateful to Dr. Dmitri
      Czerny of the Max Planck Institute for Biophysical Chemistry, Gottingen, for
      generating the electron micrograph. Our work was supported by the Max-Planck
      Gesellschaft, the BMBF together with Roche Diagnostics (grant no.: 0311003), and
      the Deutsche Forschungsgemeinschaft (grant no.: Ei 411/1-1). 

PMID- 11317293
TI  - Catalytic Asymmetric Synthesis of Epoxides from Aldehydes Using Sulfur Ylides
      with In Situ Generation of Diazocompounds We thank the EPSRC (K.M.L., M.J.P.,
      J.R.S.), Avecia for the support of a studentship (M.P.), the EU for a Marie Curie
      Fellowship (E.A.; HPMF-CT-1999-00076), and Sheffield University for financial
      support. We thank Dr. J. Blacker (Avecia), Dr. R. V. H. Jones (Zeneca
      Agrochemicals), and Dr. R. Fieldhouse (Zeneca Agrochemicals) for their interest
      in this work. 

PMID- 11317294
TI  - Application of Chiral Sulfides to Catalytic Asymmetric Aziridination and
      Cyclopropanation with In Situ Generation of the Diazo Compound We thank Avecia
      (M.P.), the EPSRC (M.F.), the EU for a Marie Curie Fellowship (E.A.; HPMF-CT-1999
      00076), Lu'an Teacher's College and the Education Minister of The Peoples
      Republic of China (G.F.), and Sheffield University for financial support. We
      thank Dr. J. Blacker (Avecia), Dr. R. V. H. Jones (Zeneca Agrochemicals), and Dr.
      R. Fieldhouse (Zeneca Agrochemicals) for their interest and support of this work.

PMID- 11317295
TI  - Oxoammonium Resins as Metal-Free, Highly Reactive, Versatile Polymeric Oxidation
      Reagents J.R. gratefully acknowledges generous support from Prof. M. E. Maier,
      Tubingen, the Strukturfonds of the Universitat Tubingen, and Merck KGaA,
      Darmstadt, Germany. 

PMID- 11317296
TI  - Thwarting beta-Hydride Elimination: Capture of the Alkylpalladium Intermediate of
      an Asymmetric Intramolecular Heck Reaction This research was supported by the
      National Institutes of Health (grant GM-12389). M.O. thanks the Deutsche
      Forschungsgemeinschaft (DFG) for an Emmy Noether fellowship (Oe 249/1-1). NMR and
      mass spectra were determined at the University of California, Irvine with
      instruments purchased with the assistance of the NSF and NIH shared
      instrumentation programs. We are grateful to Dr. Joseph W. Ziller and Dr. John
      Greaves for their assistance with X-ray structure and mass spectrometric
      analyses. 

PMID- 11317297
TI  - Complex Chemical Stabilization of Dichlorodiphosphene This work was supported by
      the Deutsche Forschungsgemeinschaft and the Fonds der Chemischen Industrie. 

PMID- 11317298
TI  - Crystal Structures from a Building Set: The First Boridecarbides of Niobium This
      work was supported by the DFG and the Fonds der Chemischen Industrie. 

PMID- 11317299
TI  - Acetylenes Rearranging on Ruthenium-Porphyrinogen and Leading to Vinylidene and
      Carbene Functionalities This work was supported by the "Fonds National Suisse de
      la Recherche Scientifique" (Grant No. 20-61 246.00). 

PMID- 11317300
TI  - A Readily Available and User-Friendly Chiral Catalyst for Efficient
      Enantioselective Olefin Metathesis This research was supported by the National
      Institutes of Health (GM-59426) and the National Science Foundation (CHE-9905806
      to A. H. H. and CHE-9988766 to R. R. S.).

PMID- 11317301
TI  - Modular Pyridinyl Peptide Ligands in Asymmetric Catalysis: Enantioselective
      Synthesis of Quaternary Carbon Atoms Through Copper-Catalyzed Allylic
      Substitutions This research was supported by the National Institutes of Health
      (GM47480 and GM57212). Additional funds were provided by DuPont. 

PMID- 11317302
TI  - Concave Butterfly-Shaped Organometallic Hydrocarbons? U.H.F.B. and M.L. thank the
      NSF for generous support (CAREER, CHE 9981765, 2000-2004). U.H.F.B. is Camille
      Dreyfus Teacher-Scholar (2000-2004). 

PMID- 11317303
TI  - Total Synthesis of (-)-Tetrazomine and Determination of Its Stereochemistry This
      work was supported by the National Institutes of Health (Grant CA85419). We are
      grateful to Yamanouchi Pharmaceutical Co. for providing a generous gift of
      natural tetrazomine. 

PMID- 11317304
TI  - Intrinsically Competitive Photoinduced Polycyclization and Double-Bond Shift
      through a Boatlike Conical Intersection This work was supported by the Universita
      di Siena (P.A.R. 99/00), the Universita di Bologna (MURST ex-60 %), NATO (CRG
      950748), and HFSP (RG 0229/2000-M). 

PMID- 11317305
TI  - An Atom-Economic Three-Carbon Chain Extension to Give Enamides We thank the
      National Science Foundation and the National Institutes of Health, General
      Medical Sciences, for their generous support of our programs and Rhone-Poulenc
      for partial financial support for J.P.S. Mass spectra were provided by the Mass
      Spectrometry Facility of the University of California, San Francisco, supported
      by the NIH Division of Research Resources. 

PMID- 11317306
TI  - Synthesis of DNA Oligomers Possessing a Covalently Cross-Linked Watson-Crick Base
      Pair Model Financial support from the National Institutes of Health (Grant: NS
      12108) is gratefully acknowledged. 

PMID- 11317307
TI  - First Total Synthesis of the Re-Type Lipopolysaccharide This work was supported
      by the Research for the Future Program (No. 97L00502) from the Japan Society for
      the Promotion of Science. H.Y. is grateful for a JSPS Research Fellowship for
      Young Scientists (No. 1241) from the Japan Society for the Promotion of Science.
      The authors are grateful to Mr. Seiji Adachi for his skillful measurement of NMR
      spectra. 

PMID- 11317308
TI  - Difluorooxymethylene-Bridged Liquid Crystals: A Novel Synthesis Based on the
      Oxidative Alkoxydifluorodesulfuration of Dithianylium Salts We thank A. Hahn and
      R. Sander for experimental assistance, and Dr. J. Krause, J. Haas, and H.
      Heldmann for the physical evaluation of the new substances. A part of the work
      presented in this article was performed under the management of the Association
      of Super-Advanced Electronics Industries (ASET) in the R&D program of the
      Japanese Ministry of International Trade and Industry (MITI) supported by the New
      Energy and Industrial Development Organization (NEDO). Another part was supported
      by the German Bundesministerium fur Bildung und Forschung (01 BM 904). 

PMID- 11317309
TI  - A Short Copper-Copper Distance in a (u-1,2-Peroxo)dicopper(II) Complex Having a
      1,8-Naphthyridine Unit as an Additional Bridge This work was supported by grants
      from the National Science Foundation and the National Institutes of Health. We
      thank A. M. Barrios for help in acquiring resonance Raman spectra. X-ray
      absorption spectroscopic data were measured at SSRL. SSRL is funded by the
      Department of Energy, Office of Basic Energy Science. The SSRL Structural
      Molecular Biology Program is supported by the National Institute of Health,
      National Center for Research Resources, Biomedical Technology Program, and by the
      Department of Energy, Office of Biological and Environmental Research. 

PMID- 11317310
TI  - Application of a Planar Chiral eta(5)-Cyclopentadienylrhenium(I)tricarbonyl
      Complex in Asymmetric Catalysis: Highly Enantioselective Phenyl Transfer to
      Aldehydes We are grateful to the Deutsche Forschungsgemeinschaft (DFG) within the
      Collaborative Research Center (SFB) 380 "Asymmetric Synthesis by Chemical and
      Biological Methods" and the Fonds der Chemischen Industrie for financial support
      and to Dr. C. W. Lehmann, MPI fur Kohlenforschung, Mulheim, for collecting the X
      ray diffraction data. M.K. acknowledges the DFG for a predoctoral fellowship
      (Graduiertenkolleg). We thank Degussa and Witco for donations of chemicals and
      Professor Dr. A. Salzer as well as Dipl.-Ing. M. Treu for inspiring discussions.
      We also appreciate the stimulus of Dr. K. Muniz for the investigation of the
      influence of the metal-pi-fragment on catalyses of this type. 

PMID- 11317311
TI  - Individual Alumina Nanotubes This work was supported by the National Natural
      Science Foundation under the contract No. 59832100. 

PMID- 11317312
TI  - Fluorinated Coiled-Coil Proteins Prepared In Vivo Display Enhanced Thermal and
      Chemical Stability This work was supported by a grant from the U.S. Army Research
      Office. Y. Tang is supported by a Whitaker Graduate Research Fellowship. We thank
      Dr. Gary Hathaway for performing matrix-assisted laser desorption/ionization
      analyses. 

PMID- 11317313
TI  - Unique Chemistry at Ice Surfaces: Incomplete Proton Transfer in the H(3)O(+)
      NH(3) System This work was supported by the Creative Research Initiatives Project
      from MOST, Republic of Korea. 

PMID- 11317314
TI  - First Example of the u(3)-eta(1),eta(2),eta(1)-C(60) Bonding Mode: Ligand-Induced
      Conversion of pi to sigma C(60)-Metal Complexes We are grateful to the National
      Research Laboratory (NRL) Program of Korean Ministry of Science & Technology
      (MOST) and the Korea Science Engineering Foundation (Project No. 1999-1-122-001
      5) for financial support of this research. 

PMID- 11317315
TI  - Expanding the Pyrimidine Diphosphosugar Repertoire: The Chemoenzymatic Synthesis
      of Amino- and Acetamidoglucopyranosyl Derivatives This contribution was supported
      by the National Institutes of Health (GM58196 and CA84374), a Cancer Center
      Support Grant (CA-08748), and a grant from the Special Projects Committee of the
      Society of Memorial Sloan-Kettering Cancer Center. J.S.T. is an Alfred P. Sloan
      Research Fellow and a Rita Allen Foundation Scholar. 

PMID- 11317316
TI  - [Ru]

PMID- 11317317
TI  - Synthesis and Characterization of RbLi(7)Ge(8) with Isolated closo-

PMID- 11317318
TI  - Controlled Synthesis of Cross-Linked Ultrathin Polymer Films by Using Surface
      Initiated Atom Transfer Radical Polymerization We thank the NSF Center for Sensor
      Materials at Michigan State University for financial support. 

PMID- 11317319
TI  - The First Phosphine Oxide Ligand Precursors for Transition Metal Catalyzed Cross
      Coupling Reactions: C-C, C-N, and C-S Bond Formation on Unactivated Aryl
      Chlorides.

PMID- 11317320
TI  - A Novel and Highly Stereoselective Intramolecular Formal

PMID- 11317321
TI  - NaV(3)(OH)(6)(SO(4))(2): A Kagome-Type Vanadium(III) Compound with Strong
      Intralayer Ferromagnetic Interactions Financial support for this work was
      provided by the National Science Foundation (DMR-9311597) and by the Center for
      Materials Science and Engineering Research at MIT (DMR-9808941). 

PMID- 11317323
TI  - A Ligand-Modulated Padlock Oligonucleotide for Supercoiled Plasmids T.R. was the
      recipient of a Bourse de Docteur Ingenieur from the CNRS. We are grateful to
      Prof. T. Garestier and J. S. Sun for helpful discussions, and to Dr. C. H. Nguyen
      for a gift of BQQ. 

PMID- 11317322
TI  - Neutral Cyclooctasulfur as a Polydentate Ligand: Supramolecular Structures of

PMID- 11317324
TI  - Selective Inclusion of a Hetero-Guest Pair in a Molecular Host: Formation of
      Stable Charge-Transfer Complexes in Cucurbit

PMID- 11317325
TI  - Template and Guest Effects on the Self-Assembly of a Neutral and Homochiral Helix
      This research was supported by the National Science Foundation (CHE-9818472) and
      the Alexander von Humboldt Foundation through a Feodor Lynen Fellowship for
      F.M.T. 

PMID- 11317327
TI  - Dual-Signaling Fluorescent Chemosensors Based on Conformational Restriction and
      Induced Charge Transfer The authors gratefully acknowledge the National Science
      Foundation for support of this research (CHE-9876333) and the Departmental NMR
      facilities (CHE-9709183), and the UC Toxic Substances Research and Teaching
      Program for support of this research. 

PMID- 11317326
TI  - Ultrafast Electron Diffraction of Transient

PMID- 11317328
TI  - Benzylic Imine Catenates: Readily Accessible Octahedral Analogues of the Sauvage
      Catenates This work was supported by the EPSRC. D.A.L. is an EPSRC Advanced
      Research Fellow (AF/982324). We thank Dr. B. P. Murphy (Manchester Metropolitan
      University) for useful discussions and Drs. T. J. Kidd, S. M. Lacy (University of
      Warwick), G. Di Orazio and R. Nasreen (University of Manchester, Institute of
      Science and Technology) for early ligand design. 

PMID- 11317329
TI  - Insertion of Helium and Molecular Hydrogen Through the Orifice of an Open
      Fullerene This work was supported by grants from the National Science Foundation.

PMID- 11317330
TI  - Substituent-dependent, positive and negative modulation of Bombyx mori adenylate
      cyclase by synthetic octopamine/tyramine analogues.
AB  - Octopamine (OCT)/tyramine (TYR) analogues, mainly including p- and beta
      substituted phenylethylamines, were prepared as probes for the ligand-binding
      site(s) of adenylate cyclase-coupled OCT or TYR receptors, and were examined for
      their effects on cAMP production in the head membranes of Bombyx mori larvae.
      Small structural changes in OCT and TYR proved to lead to three types of OCT/TYR
      analogues: (1) compounds that increase the cAMP level by themselves and also
      depress OCT-stimulated cAMP production, (2) compounds that do not stimulate cAMP
      production by themselves but inhibit OCT-stimulated cAMP production, and (3)
      compounds that are not active in either the stimulation of cAMP production or the
      inhibition of OCT-stimulated cAMP production. Tyramine, which belongs to the
      second group, also inhibited the basal level of cAMP production at high
      concentrations. The data indicate that two biogenic amine systems that positively
      and negatively regulate the level of the second messenger cAMP are present in the
      head part of B. mori larvae. This finding points to the necessity of separately
      evaluating the positive and negative regulatory effects in order to
      quantitatively understand the structure-activity relationships of OCT receptor
      ligands. Arch.

PMID- 11317331
TI  - Cloning and expression of a ferritin subunit for Galleria mellonella.
AB  - Ferritin was purified from iron-fed Galleria mellonella hemolymph by ultra
      centrifugation and FPLC (Superose 6). SDS-PAGE revealed three bands of 26, 30,
      and 32 kDa. The ferritin 26 kDa subunit cDNA was obtained from RT-PCR using
      primer designed from N-terminal sequence analysis. 5'-RACE was used to obtain the
      complete protein coding sequence. The sequence encodes a 211 amino acid
      polypeptide including a 20 amino acid leader peptide. An IRE (iron-responsive
      element) sequence with a predicted stem-loop structure was present in the 5'-UTR
      of ferritin mRNA. Sequence alignment has a sequence identity with Calpodes
      ethlius (S)(74%), Drosophila melanogaster (50%), and Aedes aegypti (39%).
      Northern blot analysis indicated that there were 1.5- and 1.75-fold increases in
      the expression of ferritin mRNA after iron-fed fat body and midgut, respectively.
      Also, we confirmed that the ferritin mRNA is not expressed in adult ovary and
      testis. Arch.

PMID- 11317332
TI  - Differences in midgut serine proteinases from larvae of the bruchid beetles
      Callosobruchus maculatus and Zabrotes subfasciatus.
AB  - Proteinase activities in the larval midguts of the bruchids Callosobruchus
      maculatus and Zabrotes subfasciatus were investigated. Both midgut homogenates
      showed a slightly acidic to neutral pH optima for the hydrolysis of fluorogenic
      substrates. Proteolysis of epsilon-aminocaproil-Leu-Cys(SBzl)-MCA was totally
      inhibited by the cysteine proteinase inhibitors E-64 and leupeptin, and was
      activated by 1.5 mM DTT in both insects, while hydrolysis of the substrate Z
      ArgArg-MCA was inhibited by aprotinin and E-64, which suggests that it is being
      hydrolysed by serine and cysteine proteinases. Gel assays showed that the
      proteolytic activity in larval midgut of C. maculatus was due to five major
      cysteine proteinases. However, based on the pattern of E-64 and aprotinin
      inhibition, proteolytic activity in larval midgut of Z. subfasciatus was not due
      only to cysteine proteinases. Fractionation of the larval midgut homogenates of
      both bruchids through ion-exchange chromatography (DEAE-Sepharose) revealed two
      peaks of activity against Z-ArgArg-MCA for both bruchid species. The fractions
      from C. maculatus have characteristics of cysteine proteinases, while Z.
      subfasciatus has one non-retained peak of activity containing cysteine
      proteinases and another eluted in a gradient of 250-350 mM NaCl. The proteolytic
      activity of the retained peak is higher at pH 8.8 than at pH 6.0 and corresponds
      with a single peak that is active against N-p-tosyl-GlyGlyArg-MCA, and sensitive
      to 250 microM aprotinin (90% inhibition). The peak contains a serine proteinase
      which hydrolyzes alpha-amylase inhibitor 1 from the common bean (Phaseolus
      vulgaris). Arch.

PMID- 11317333
TI  - Regulation of hexokinase in a freeze avoiding insect: role in the winter
      production of glycerol.
AB  - Hexokinase from larvae of the freeze-avoiding goldenrod gall moth, Epiblema
      scudderiana, was purified 20-fold using chromatography on DE52 Sephadex,
      phosphocellulose, and blue dextran. Final specific activity was 75.8 U/mg and SDS
      PAGE gave a molecular weight of 94,000 for the monomer. Arrhenius plot showed a
      break at 16 degrees or 12 degrees C in the absence vs. presence of 10% v/v
      glycerol, indicating a conformational change in the enzyme at lower temperatures
      but suggesting a stabilizing effect of glycerol. Comparison of hexokinase kinetic
      properties at 22 degrees and 4 degrees C showed higher affinity for both glucose
      and ATP (Km values were 45-50% lower), as well as for the cofactor Mg(2+), at the
      lower temperature. Furthermore, product inhibition by glucose-6-phosphate and ADP
      was reduced at 4 degrees C. Glucose levels rise in E. scudderiana as an apparent
      by-product of high rates of glycogenolysis during glycerol synthesis. The
      temperature-dependent properties of hexokinase would facilitate the recycling of
      this glucose back into the pathway of glycerol synthesis and could help to
      achieve the near stoichiometric conversion of glycogen to glycerol that is seen
      during cold hardening. Arch.

PMID- 11317334
TI  - Sex pheromone levels in pheromone glands and identification of the pheromone and
      hydrocarbons in the hemolymph of the moth Scoliopteryx libatrix L. (Lepidoptera:
      Noctuidae).
AB  - The hydrocarbon sex pheromone (13-methyl-Z6-heneicosene) of Scoliopteryx libatrix
      L. (Lepidoptera: Noctuidae) was found to reach its highest levels on pheromone
      glands of 3-day-old females. Pheromone levels were not different between the time
      of maximum calling (end of scotophase) and at the middle of photophase.
      Overwintering females collected in October had sex pheromone present.
      Decapitation did not lower the amount of pheromone present, indicating that a
      head factor is not involved in maintaining pheromone titers. Hemolymph also
      contained the pheromone, indicating that it is made by oenocytes and transported
      to the sex pheromone gland. Longer chain length hydrocarbons were also identified
      from the hemolymph and on the cuticular surface. Quantitative differences in
      hydrocarbon profiles were found with more methyl-branched hydrocarbons found in
      the hemolymph than on the cuticular surface. Arch.

PMID- 11317335
TI  - Effect of pharmacogenetics on medicine.
AB  - Pharmacogenetics is moving rapidly to assemble a large set of polymorphisms that
      define the influence of genetic diversity on human drug response. Scientific and
      technological advances of the last 10 years have led to new approaches to the
      discovery of genetic drug susceptibility loci, the development of high-tech
      analytical strategies for drug susceptibility profiling, and a flood of new gene
      discoveries in the area of receptors and receptor polymorphisms. Extension and
      refinement of our knowledge of human genetic diversity is essential to the use of
      drugs in more of an individualized manner and to the discovery of better
      therapies, but knowledge of the functional consequences of this diversity, the
      next great challenge in pharmacogenetics, provides the best chance to profit from
      this diversity.

PMID- 11317336
TI  - Dermal benzene and trichloroethylene induce aneuploidy in immature hematopoietic
      subpopulations in vivo.
AB  - Accumulation of genetic damage in long-lived cell populations with proliferative
      capacity is implicated in tumorigenesis. Hematopoietic stem cells (hsc) maintain
      lifetime hematopoiesis, and recent studies demonstrate that hsc in leukemic
      patients are cytogenetically aberrant. We postulated that exposure to agents
      associated with increased leukemia risk would induce genomic changes in cells in
      the hsc compartment. Aneusomy involving chromosomes 2 and 11 in sorted hsc (Lin(
      )c-kit(+)Sca-1(+)) and maturing lymphoid and myeloid cells from mice that
      received topical doses of benzene (bz) or trichloroethylene (TCE) was quantified
      using fluorescence in situ hybridization. Six days after bz or TCE exposure,
      aneuploid cells in the hsc compartment increase four- to eightfold in a dose- and
      schedule-independent manner. Aneuploid lymphoid and myeloid cells from bz- and
      TCE-treated mice approximate controls, except after repeated benzene exposures.
      Aneuploid cells are more frequent in the hsc compartment than in mature
      hematopoietic subpopulations. Hematotoxicity was also quantified in bz- and TCE
      exposed hematopoietic subpopulations using two colony-forming assays: CFU-GM
      (colony-forming units/granulocyte-macrophage progenitors) and CAFC (cobblestone
      area-forming cells). Data indicate that bz is transiently cytotoxic (< or =1
      week) to hsc subpopulations, and induces more persistent toxicity (>2 weeks) in
      maturing, committed progenitor subpopulations. TCE is not hematotoxic at the
      doses applied. In conclusion, we provide direct evidence for induction of
      aneuploidy in cells in the hsc compartment by topical exposure to bz and TCE.
      Disruption of genomic integrity and/or toxicity in hsc subpopulations may be one
      step in leukemic progression.

PMID- 11317337
TI  - Comparison of hprt and lacI mutant frequency with DNA adduct formation in N
      hydroxy-2-acetylaminofluorene-treated Big Blue rats.
AB  - N-Hydroxy-2-acetylaminofluorene (N-OH-AAF) is the proximate carcinogenic
      metabolite of the powerful rat liver carcinogen 2-acetylaminofluorene. In this
      study, transgenic Big Blue(R) rats were used to examine the relationship between
      in vivo mutagenicity and DNA adduct formation by N-OH-AAF in the target liver
      compared with that in nontarget tissues. Male rats were given one, two, or four
      doses of 25 mg N-OH-AAF/kg body weight by i.p. injection at 4-day intervals, and
      groups of treated and control rats were euthanized up to 10 weeks after beginning
      the dosing. Mutant frequencies were measured in the spleen lymphocyte hprt gene,
      and lacI mutant frequencies were determined in the liver and spleen lymphocytes.
      At 6 weeks after beginning the dosing, the hprt mutant frequency in spleen
      lymphocytes from the four-dose group was 16.5 x 10(-6) compared with 3.2 x 10(-6)
      in control animals. Also at 6 weeks, rats given one, two, or four doses of N-OH
      AAF had lacI mutant frequencies in the liver of 97.6, 155.6, and 406.8 x 10(-6),
      respectively, compared with a control frequency of 25.7 x 10(-6); rats given four
      doses had lacI mutant frequencies in spleen lymphocytes of 55.8 x 10(-6) compared
      with a control frequency of 20.4 x 10(-6). Additional rats were evaluated for DNA
      adduct formation in the liver, spleen lymphocytes, and bone marrow by (32)P
      postlabeling. Adduct analysis was conducted 1 day after one, two, and four
      treatments with N-OH-AAF, 5 days after one treatment, and 9 days after two
      treatments. N-(Deoxyguanosin-8-yl)-2-aminofluorene was the major DNA adduct
      identified in all the tissues examined. Adduct concentrations increased with
      total dose to maximum values in samples taken 1 day after two doses, and remained
      essentially the same after four doses. In samples taken after four doses, adduct
      levels were 103, 28, and 7 fmol/microg of DNA in liver, spleen lymphocytes, and
      bone marrow, respectively. The results indicate that the extent of both DNA
      adduct formation and mutant induction correlates with the organ specificity for N
      OH-AAF carcinogenesis in the rat. Environ. Mol. Mutagen. 37:195-202, 2001.
      Published 2001 Wiley-Liss, Inc.

PMID- 11317338
TI  - Gene- and tissue-specificity of mutation in Big Blue rats treated with the
      hepatocarcinogen N-hydroxy-2-acetylaminofluorene.
AB  - In a previous study, we found that treating transgenic Big Blue rats with the
      hepatocarcinogen N-hydroxy-2-acetylaminofluorene (N-OH-AAF) produced the same
      major DNA adduct in the target liver and the nontarget spleen lymphocytes and
      bone marrow cells, induced lacI mutants in the liver, and induced much lower
      frequencies of lacI and hprt mutants in spleen lymphocytes. In the present study,
      sequence analysis was conducted on lacI DNA and hprt cDNA from the mutants, to
      determine the mutational specificity of N-OH-AAF in the rat. All the mutation
      spectra from N-OH-AAF-treated rats differed significantly from corresponding
      mutation profiles from untreated animals (P = 0.02 to P < 0.0001). Although there
      were similarities among the mutational patterns derived from N-OH-AAF-treated
      rats (e.g., G:C --> T:A transversion was the most common mutation in all mutation
      sets), there were significant differences in the patterns of basepair
      substitution and frameshift mutation between the liver and spleen lymphocyte lacI
      mutants (P = 0.02) and between the spleen lymphocyte lacI and hprt mutants (P =
      0.04). Also, multiplex PCR analysis of genomic DNA from the hprt mutants
      indicated that 12% of mutants from treated rats had major deletions in the hprt
      gene; no corresponding incidence of large deletions was evident among lacI
      mutations. All the mutation profiles reflect the general mutational specificity
      of the major DNA adduct formed by N-OH-AAF. The differences between N-OH-AAF
      mutation in the endogenous gene and transgene can be partially explained by the
      structures of the two genes. The tissue-specificity of the mutation spectra may
      contribute to targeting tumor formation to the liver. Environ. Mol. Mutagen.
      37:203-214, 2001. Published 2001 Wiley-Liss, Inc.

PMID- 11317339
TI  - Usefulness of genetic susceptibility and biomarkers for evaluation of
      environmental health risk.
AB  - Recent attention is focused on understanding the genetic basis for individual
      susceptibility to the development of chronic disease. An emphasis is concentrated
      on establishing an association between inheritance of polymorphic chemical
      metabolizing genes and development of environmental cancer (e.g., lung cancer
      among cigarette smokers). The early reports of such associations have been very
      encouraging. However, some reported positive associations were not substantiated
      in subsequent studies using larger sample sizes and different ethnic populations.
      In this review, some confounding factors that contribute to the discrepancies are
      presented (e.g., ethnic-dependent distribution of variant gene alleles,
      differential expression of metabolizing genes, and inadequate study design). It
      is possible that the precision of the association can be improved if the
      mentioned investigations are complemented with concurrent studies of biological
      activities/effects. The usefulness of integrating metabolic susceptibility with
      biomarker measurement for understanding the development of lung cancers is
      presented. The importance of using adequate sample size and experimental design
      is emphasized. Development of a reliable approach for prediction of environmental
      disease not only will provide fundamental information regarding the genetic basis
      of human disease but will be useful for reducing disease burden in the population
      and for advancing patient care. Environ. Mol. Mutagen. 37:215-225, 2001. &copy
      2001 Wiley-Liss, Inc.

PMID- 11317340
TI  - DNA adducts of 1,3-butadiene in humans: relationships to exposure, GST genotypes,
      single-strand breaks, and cytogenetic end points.
AB  - The modulation of 1,3-butadiene (BD)-induced DNA adducts by occupational
      exposure, glutathione S-transferase (GST) genotypes, single-strand breaks, and
      cytogenetic end points was studied in 15 workers and 11 controls. The exposed
      group consisted of 8 smokers and 7 nonsmokers, whereas the control group
      consisted of 7 nonsmokers and 4 smokers. Among all subjects, the adduct levels in
      workers lacking GSTM1 were significantly higher than in those who were GSTM1
      positive (P = 0.026), and individuals with combined GSTM1(-) and GSTT1(+)
      genotype had elevated level of adducts compared to that of persons with GSTM1(+)
      and GSTT1(+) (P = 0.049). The increase in BD-DNA adduct levels in all subjects
      was significantly related to BD exposure and GSTM1 genotype (linear multiple
      regression analysis, P = 0.001; P = 0.035). The results suggest that DNA adducts
      serve as a sensitive and specific biomarker, integrating exposure and host
      metabolic capacity, although the data are limited to a small number of subjects.

PMID- 11317341
TI  - In vitro prediction of carcinogenicity using a bovine papillomavirus DNA-
      carrying C3H/10T 1/2 cell line (T1). II: Results from the testing of 100
      chemicals.
AB  - A new in vitro test for identifying carcinogens is evaluated against a testing
      database of 100 chemicals including the following groups: steroids,
      antineoplastics, PCBs, dioxins, alkyl halides, aromatic amines, nitrogen
      heterocycles, polyaromatic hydrocarbons, mustards, and benzodioxoles. The assay
      uses focus formation in a stable, BPV-1-DNA-carrying C3H/10T 1/2 mouse embryo
      fibroblast cell line (T1), which does not require transfection, infection with
      virus, or isolation of primary cells from animals. For this group of chemicals,
      the T1 assay correctly predicted the rodent carcinogenicity or noncarcinogenicity
      of 77% of the chemicals for which carcinogenicity is reported. Based on published
      data the bacterial mutagenicity assay would have correctly predicted
      carcinogenicity or noncarcinogenicity of 53% of the chemicals. The Syrian hamster
      embryo test would have correctly predicted carcinogenicity or noncarcinogenicity
      of 61% of the chemicals. We also demonstrate dose--response relationships for two
      of the chemicals. We report the responses of T1 cells to the group of chemicals
      used in the International Life Sciences Institute's program for screening of
      alternative methods of predicting carcinogenicity.

PMID- 11317342
TI  - Human DNA repair genes.
AB  - DNA repair systems are essential for the maintenance of genome integrity.
      Consequently, the disregulation of repair genes can be expected to be associated
      with significant, detrimental health effects, which can include an increased
      prevalence of birth defects, an enhancement of cancer risk, and an accelerated
      rate of aging. Although original insights into DNA repair and the genes
      responsible were largely derived from studies in bacteria and yeast, well over
      125 genes directly involved in DNA repair have now been identified in humans, and
      their cDNA sequence established. These genes function in a diverse set of
      pathways that involve the recognition and removal of DNA lesions, tolerance to
      DNA damage, and protection from errors of incorporation made during DNA
      replication or DNA repair. Additional genes indirectly affect DNA repair, by
      regulating the cell cycle, ostensibly to provide an opportunity for repair or to
      direct the cell to apoptosis. For about 70 of the DNA repair genes listed in
      Table I, both the genomic DNA sequence and the cDNA sequence and chromosomal
      location have been elucidated. In 45 cases single-nucleotide polymorphisms have
      been identified and, in some cases, genetic variants have been associated with
      specific disorders. With the accelerating rate of gene discovery, the number of
      identified DNA repair genes and sequence variants is quickly rising. This report
      tabulates the current status of what is known about these genes. The report is
      limited to genes whose function is directly related to DNA repair.

PMID- 11317343
TI  - Simultaneous analysis of enantiomeric composition of amino acids and N-acetyl
      amino acids by enantioselective chromatography.
AB  - Among the three chiral columns, CHIROBIOTIC T, CHIRLPAK WH, and CHIRALCEL OD-R,
      tested for the separation of racemic amino acids and N-acetyl-amino acids, only
      CHIROBIOTIC T chiral column which is based on covalently bonded amphoteric
      glycopeptide, teicoplanin, as the stationary phase ligand could be successfully
      developed to enantiomerically separate racemic amino acids and N-acetyl amino
      acids simultaneously. This method can be used to determine the enantiomeric
      composition of amino acids and N-acetyl-amino acids in the catalysis of D
      aminoacylase or L-aminoacylase and the conversion rate of N-acylamino acid
      racemases.

PMID- 11317344
TI  - Stereoselective binding and degradation of sulbenicillin in the presence of human
      serum albumin.
AB  - Binding of sulbenicillin (SBPC) isomers to human serum albumin (HSA) was
      stereoselective. There were at least two classes of binding sites on HSA for SBPC
      isomers. At the stereoselective high affinity site, binding was in favor of R
      SBPC, the binding constant of R-SBPC being approximately 2.3-fold greater than
      that of S-SBPC. By using site marker ligands, it was revealed that the
      stereoselective site was Site I (warfarin binding site). Affinity for the low
      affinity (nonstereoselective) site was similar for the diastereomers,
      approximately 7--30-fold lower than for the stereoselective site. R-SBPC and S
      SBPC appeared to displace each other competitively at both binding sites. On the
      other hand, R-SBPC was degraded much faster than S-SBPC in the presence of HSA,
      with a degradation rate constant approximately 7-fold greater for R-SBPC than for
      S-SBPC. The degradation of R-SBPC was inhibited in the presence of warfarin and
      dependent on the concentration of R-SBPC bound to Site I. The results demonstrate
      that Site I is responsible for the stereoselective degradation.

PMID- 11317345
TI  - Discrimination in resolving systems. VI. Comparison of the diastereomers of
      deoxyephedrinium and ephedrinium 4'-fluoromandelates.
AB  - (-)-(R)-Deoxyephedrine forms poorly discriminating diastereomeric salts with 4'
      fluoromandelic acid from 95% ethanol. Both less-soluble (L) (S)-4'
      fluoromandelate and more-soluble (M) (R)-4'-fluoromandelate phases are monoclinic
      and unsolvated. Their solubility ratio (M/L) in 95% ethanol is only 1.2, which
      correlates with the similarity and small differences in their respective heats of
      fusion and fusion temperatures. The (R)-deoxyephedrinium and the related (1R;2S)
      ephedrinium 4'-fluoromandelate systems show L-salts with higher ion-pair volumes
      and lower densities than their M-salts. (R)-Deoxyephedrinium salts have higher
      volumes than the comparable (1R;2S)-ephedrinium salts even though the resolving
      base (R)-deoxyephedrine lacks the benzylic hydroxy. In the solids, bilayered
      structures segregate polar and nonpolar molecular regions. The principle
      interionic interactions are hydrogen bonds between protonated secondary ammonium
      ions and carboxylates forming infinite chains with a six-atom repeating unit H
      N(+)-H...O-C(-)-O [C(2)(2)(6)]. These are buttressed by mandelate hydroxy to
      carboxylate hydrogen bonds. Differing interactions between phenyl and 4'
      fluorophenyl rings in the nonpolar layers of the salts correlate with the density
      and stability inversion.

PMID- 11317346
TI  - Chirality inversion in the bilirubin molecular exciton.
AB  - The bichromophoric pigment bilirubin acts as a molecular exciton in its UV
      visible and circular dichroism (CD) spectroscopy. In both polar and nonpolar
      solvents, an optically active analog, (beta R,beta 'R)-dimethylmesobilirubin-XIII
      alpha (1), exhibits intense bisignate CD Cotton effects in the region of its long
      wavelength UV-vis absorption near 400 nm: Delta epsilon(434)(max) + 337, Delta
      epsilon(389)(max) - 186 (CHCl(3)), and Delta epsilon(431)(max) + 285, Delta
      epsilon(386)(max) - 177 (CH(3)OH). However, introduction of an amine into a
      CHCl(3) solution of 1 causes the Cotton effect signs to become inverted, e.g.,
      after addition of NH(3), Delta epsilon(433)(max) - 345, Delta epsilon(389)(max) +
      243, and after addition of ethylene diamine, Delta epsilon(435)(max) - 420, Delta
      epsilon(390)(max) + 299. The sign inversions imply inversion of molecular
      chirality of the bilirubin and the phenomenon appears to be general for amines,
      including alpha,omega-diamines. 1,8-Diaminooctane was found to be more effective
      than longer or shorter chain analogs in producing CD sign inversion.

PMID- 11317347
TI  - Synthesis and stereochemical characterization of optically active 1,2
      diarylethane-1,2-diols: useful chiral controllers in the Ti-mediated
      enantioselective sulfoxidation.
AB  - The series of phenylsubstituted 1,2-diphenylethane-1,2-diols 2a-h was prepared in
      high chemical (70--80%) and optical yields (approximately 90%) by Sharpless syn
      dihydroxylation of the corresponding (E)-1,2-diarylethenes, in turn obtained by
      McMurry or Wittig reactions. The enantiomeric excesses of the samples were
      determined by HPLC analysis using Chiralcel OD chiral stationary phase (CSP).
      This CSP was able to resolve all the diols, except for 2g, with alpha values
      ranging between 1.10--1.64. In all cases the (R,R) antipode was eluted first.
      (R,R) absolute configuration was assigned to the dextrorotatory (CHCl(3)) diols
      2a--h by analyzing the CD spectra of their 2,2-dimethyl-1,3-dioxolanes 3a--h. In
      fact, the CD spectra of all these dioxolanes present a positive couplet (210--180
      nm range) which can be nonempirically related to an (R,R) absolute configuration
      of the two stereocenters.

PMID- 11317348
TI  - CD exciton chirality method for determination of the absolute configuration of
      beta-hydroxy-alpha-amino acid derivatives.
AB  - The absolute configuration of beta-hydroxy-alpha-amino acids was studied by CD
      exciton chirality method using 7-diethylaminocoumarin-3-carboxylate as a red
      shifted chromophore. The CD spectra of bischromophoric derivatives of (S)-serine
      and (2S,3R)-threonine methyl esters (2 and 7) were compared with those of acyclic
      vic-aminoalcohols and diols (3--6 and 8--9). This study indicates that the polar
      carboxylate group of beta-hydroxy-alpha-amino acids makes them a unique subclass
      of vic-aminoalcohols. By combining the data of CD and NMR coupling constants, we
      are able to correlate their preferred conformer B and positive CD to the
      corresponding absolute configuration.

PMID- 11317349
TI  - Solvent-dependent enantioselective interaction of some bis-allylamide chiral
      selectors studied by NMR.
AB  - A series of chiral selectors, all of them bis-allylamides of C(2)-symmetric
      dicarboxylic acids, were studied by NMR in different solvents in an attempt to
      affect the equilibria between free selector and the diastereomeric complexes
      formed by its interaction with the (+)- and (-)-forms of O,O'-dibenzoyltartaric
      acid (DBTA). The results show that by changing the polarity of the solvent the
      equilibria are displaced, as observed from changing chemical shift differences.
      Phase-sensitive (1)H[(1)H]-NOESY experiments revealed different interactions
      between the chiral selector and the analyte enantiomers. The individual
      equilibrium constants were determined by separate studies of the equilibria
      between the selector and the respective enantiomers of the chiral DBTA probe.

PMID- 11317350
TI  - WFS1/wolframin mutations, Wolfram syndrome, and associated diseases.
AB  - Wolfram syndrome (WS) is the inherited association of juvenile-onset insulin
      dependant diabetes mellitus and progressive bilateral optic atrophy. A nuclear
      gene, WFS1/wolframin, was identified that segregated with disease status and
      demonstrated an autosomal recessive mode of inheritance. Mutation analysis of the
      WFS1 gene in WS patients has identified mutations in 90% of patients. Most were
      compound heterozygotes with private mutations distributed throughout the gene
      with no obvious hotspots. The private nature of the mutations in WS patients and
      the low frequencies make it difficult to determine the biological or clinical
      relevance of these mutations. Mutation screening in patients with psychiatric
      disorders or diabetes mellitus has also been performed to test the hypothesis
      that heterozygous carriers of WFS1 gene mutations are at an increased risk
      following the observation that WS first-degree relatives have a higher frequency
      of these disorders. Most studies showed no association, however two missense
      mutations were identified that demonstrated significant association with
      psychiatric disorders and diabetes mellitus. Population association studies and
      functional studies of these variants will need to be performed to confirm these
      preliminary results. The elucidation of functions and functional pathways for the
      WFS1 gene product and variants will shed light on the effect of such disparate
      mutations on gene function and their role in the resulting clinical phenotype in
      WS and associated disorders.

PMID- 11317351
TI  - Mutation spectrum in the nephrin gene (NPHS1) in congenital nephrotic syndrome.
AB  - Congenital nephrotic syndrome, Finnish type (CNF or NPHS1), is an autosomal
      recessive disease characterized by massive proteinuria and development of
      nephrotic syndrome shortly after birth. The disease is most common in Finland,
      but many patients have been identified in other populations. The disease is
      caused by mutations in the gene for nephrin which is a key component of the
      glomerual ultrafilter, the podocyte slit diaphragm. A total of 30 mutations have
      been reported in the nephrin gene in patients with congenital nephrotic syndrome
      worldwide. In the Finnish population, two main mutations have been found. These
      two nonsense mutations account for over 94% of all mutations in Finland. Most
      mutations found in non-Finnish patients are missense mutations, but they include
      also nonsense and splice site mutations, as well as deletions and insertions.
      This mutation update summarizes the nature of all previously reported nephrin
      mutations and, additionally, describes 20 novel mutations recently identified in
      our laboratory.

PMID- 11317352
TI  - Mutations in the SURF1 gene associated with Leigh syndrome and cytochrome C
      oxidase deficiency.
AB  - Cytochrome c oxidase (COX) deficiency is one of the major causes of Leigh
      Syndrome (LS), a fatal encephalopathy of infancy or childhood, characterized by
      symmetrical lesions in the basal ganglia and brainstem. Mutations in the nuclear
      genes encoding COX subunits have not been found in patients with LS and COX
      deficiency, but mutations have been identified in SURF1. SURF1 encodes a factor
      involved in COX biogenesis. To date, 30 different mutations have been reported in
      40 unrelated patients. We aim to provide an overview of all known mutations in
      SURF1, and to propose a common nomenclature. Twelve of the mutations were
      insertion/deletion mutations in exons 1, 4, 6, 8, and 9; 10 were
      missense/nonsense mutations in exons 2, 4, 5, 7, and 8; and eight were detected
      at splicing sites in introns 3 to 7. The most frequent mutation was 312_321del
      311_312insAT which was found in 12 patients out of 40. Twenty mutations have been
      described only once. We also list all polymorphisms discovered to date.

PMID- 11317353
TI  - Variable expressivity and mutation databases: The androgen receptor gene
      mutations database.
AB  - For over 50 years genetics has presumed that variations in phenotypic expression
      have, for the most part, been the result of alterations in genotype. The
      importance and value of mutation databases has been based on the premise that the
      same gene or allelic variation in a specific gene that has been proven to
      determine a specific phenotype, will always produce the same phenotype. However,
      recent evidence has shown that so called "simple" Mendelian disorders or
      monogenic traits are often far from simple, exhibiting phenotypic variation
      (variable expressivity) that cannot be explained solely by a gene or allelic
      alteration. The AR gene mutations database now lists 25 cases where different
      degrees of androgen insensitivity are caused by identical mutations in the
      androgen receptor gene. In five of these cases the phenotypic variability is due
      to somatic mosaicism, that is, somatic mutations that occur in only certain cells
      of androgen-sensitive tissue. Recently, a number of other cases of variable
      expressivity have also been linked to somatic mosaicism. The impact of variable
      expressivity due to somatic mutations and mosaicism on mutation databases is
      discussed. In particular, the effect of an organism exhibiting genetic
      heterogeneity within its tissues, and the possibility of an organism's genotype
      changing over its lifetime, are considered to have important implications for
      mutation databases in the future.

PMID- 11317354
TI  - Germline and somatic mutation analyses in the DNA mismatch repair gene MLH3:
      Evidence for somatic mutation in colorectal cancers.
AB  - DNA mismatch repair is of considerable scientific and medical importance because
      of its essential role in maintaining genomic integrity, and its association with
      hereditary non-polyposis colon cancer (HNPCC). Germline mutations in five
      mismatch repair genes (MLH1, MSH2, PMS1, PMS2, and MSH6) have been associated
      with HNPCC susceptibility. Our laboratory recently identified MLH3, a novel DNA
      mismatch repair gene. We screened the MLH3 coding sequence in 60 probands with
      increased genetic risk factors for colorectal cancer susceptibility and no
      mutations in the other candidate genes. No definite MLH3 germline mutations were
      found. We subsequently screened 36 colon tumors, and discovered an appreciable
      frequency of somatic MLH3 coding mutations in MSI-H tumors (25%). In four of six
      tumors, evidence of biallelic inactivation was noted. Furthermore, MLH3 nonsense
      mutations were identified in two of 12 microsatellite stable (MSS) tumors with
      14q24 loss of heterozygosity. While our analyses do not exclude the existence of
      germline MLH3 mutations in patients with increased genetic risk factors for
      colorectal cancer susceptibility, they suggest such mutations are uncommon in
      this patient population. The finding of an appreciable frequency of somatic MLH3
      mutations is consistent with a possible role for this gene in the progression of
      colorectal cancer tumorigenesis. Hum Mutat 17:389-396, 2001. Published 2001 Wiley
      Liss, Inc.

PMID- 11317355
TI  - Mucolipidosis type IV: novel MCOLN1 mutations in Jewish and non-Jewish patients
      and the frequency of the disease in the Ashkenazi Jewish population.
AB  - The gene MCOLN1 is mutated in Mucolipidosis type IV (MLIV), a neurodegenerative,
      recessive, lysosomal storage disorder. The disease is found in relatively high
      frequency among Ashkenazi Jews due to two founder mutations that comprise 95% of
      the MLIV alleles in this population [Bargal et al., 2000]. In this report we
      complete the mutation analysis of Jewish and non-Jewish MLIV patients whose DNA
      were available to us. Four novel mutations were identified in the MCOLN1 gene of
      severely affected patients: two missense, T232P and F465L; a nonsense, R322X; and
      an 11-bp insertion in exon 12. The nonsense mutation (R322X) was identified in
      two unrelated patients with different haplotypes in the MCOLN1 chromosomal
      region, indicating a mutation hotspot in this CpG site. An in-frame deletion
      (F408del) was identified in a patient with unusual mild psychomotor retardation.
      The frequency of MLIV in the general Jewish Ashkenazi population was estimated in
      a sample of 2,000 anonymous, unrelated individuals assayed for the two founder
      mutations. This analysis indicated a heterozygotes frequency of about 1/100. A
      preferred nucleotide numbering system for MCOLN1 mutations is presented and the
      issue of a screening program for the detection of high-risk families in the
      Jewish Ashkenazi population is discussed.

PMID- 11317356
TI  - Pendred syndrome, DFNB4, and PDS/SLC26A4 identification of eight novel mutations
      and possible genotype-phenotype correlations.
AB  - Mutations in PDS (SLC26A4) cause both Pendred syndrome and DFNB4, two autosomal
      recessive disorders that share hearing loss as a common feature. The hearing loss
      is associated with temporal bone abnormalities, ranging from isolated enlargement
      of the vestibular aqueduct (dilated vestibular aqueduct, DVA) to Mondini
      dysplasia, a complex malformation in which the normal cochlear spiral of 2(1/2)
      turns is replaced by a hypoplastic coil of 1(1/2) turns. In Pendred syndrome,
      thyromegaly also develops, although affected persons usually remain euthyroid. We
      identified PDS mutations in the proband of 14 of 47 simplex families (30%) and
      nine of 11 multiplex families (82%) (P=0.0023). In all cases, mutations
      segregated with the disease state in multiplex families. Included in the 15
      different PDS allele variants we found were eight novel mutations. The two most
      common mutations, T416P and IVS8+1G>A, were present in 22% and 30% of families,
      respectively. The finding of PDS mutations in five of six multiplex families with
      DVA (83%) and four of five multiplex families with Mondini dysplasia (80%)
      implies that mutations in this gene are the major genetic cause of these temporal
      anomalies. Comparative analysis of phenotypic and genotypic data supports the
      hypothesis that the type of temporal bone anomaly may depend on the specific PDS
      allele variant present.

PMID- 11317357
TI  - Spectrum of germline RB1 gene mutations in Spanish retinoblastoma patients:
      Phenotypic and molecular epidemiological implications.
AB  - Mutation analysis of retinoblastoma is considered important for genetic
      counseling purposes, as well as for understanding the molecular mechanisms
      leading to tumors with different degrees of penetrance or expressivity. In the
      course of an analysis of 43 hereditary retinoblastoma Spanish patients and
      kindred, using direct PCR sequencing, we have observed 29 mutations; most of them
      (62%) have not been reported previously. Of the mutations, 69% correspond to
      nonsense mutations (mainly CpG transitions) and frameshifts, with the expected
      outcome of a truncated Rb protein that lacks the functional pocket domains and
      tail. The remainder corresponds to splicing mutations, most of them (62%)
      targeted to invariant nucleotides, with the predicted consequence of out of frame
      exon skipping. Two of the splicing mutations in our study were found associated
      to families with a low-penetrance phenotype. Additionally, most of the mutations
      affecting splice junctions corresponded to retinoblastoma cases of either
      sporadic or hereditary nature with delayed onset (32 months on average). In
      contrast, most of the nonsense and frameshift mutations are associated with an
      early age at diagnosis (8.7 months on average). These differences are discussed
      in the context of the relationships between genotype and low expressivity
      phenotype. The differences in the spectrum of RB1 mutations found in this and
      other European surveys are also discussed in the context of alternate DNA
      methylation and mismatch repair phenotypes.

PMID- 11317358
TI  - A novel MSP/DHPLC method for the investigation of the methylation status of
      imprinted genes enables the molecular detection of low cell mosaicisms.
AB  - We describe a new procedure for the analysis of the methlyation status of
      imprinted genes based on methylation-specific PCR followed by denaturing high
      performance liquid chromatography (MSP/DHPLC). The method offers a rapid and very
      reliable alternative to conventional methods used for such purposes such as
      Southern blots and methylation specific PCR (allele-specific MSP). The efficient
      resolution of the differentially methylated alleles is demonstrated for two human
      imprinted genes, namely the SNRPN gene and the LIT1 gene (KCNQ1OT1). Abnormal
      imprinting of the two genes is associated with the Angelman/Prader-Willi
      syndromes and the Beckwith-Wiedemann syndrome, respectively. The MSP/DHPLC method
      is based on PCR amplification of gene segments which show parent-of-origin
      specific methylation. Genomic DNA is subjected to an in vitro bisulfite treatment
      prior to PCR amplifications using primers specific for modified DNA. Both alleles
      are theoretically amplified with equal efficiency and are represented by
      identically sized PCR products; they differ, however, at a number of positions
      within the amplified DNA segment. The DHPLC analysis allows a very efficient
      resolution of the two populations of PCR products. The high sensitivity and
      quantitative properties of the MSP/DHPLC method are illustrated based on its
      ability to reveal a low cell mosaicism in an infant with a maternal uniparental
      disomy 15 (i.e., Prader-Willi syndrome patient). The minor cell line
      (approximately 8% in blood) was not detectable with conventional molecular
      analysis. While the detection of low cell mosaicisms of structurally abnormal
      chromosomes usually relies on cytogenetic studies, the MSP/DHPLC method described
      here not only offers an alternative at the molecular level, but may also reveal
      mosaicisms concerning structurally intact chromosomes.

PMID- 11317361
TI  - Characterization and geographic distribution of the low density lipoprotein
      receptor (LDLR) gene mutations in northwestern Greece.
AB  - Familial Hypercholesterolaemia (FH) is a clinical syndrome characterised by
      elevated serum total cholesterol levels due to an increase in low density
      lipoprotein (LDL) cholesterol, by tendon xanthomata and clinical manifestations
      of ischaemic heart disease in early life. Typically, it results from mutations in
      the low-density lipoprotein receptor (LDLR) gene. So far, over 600 mutations have
      been reported for the LDLR gene and account for FH. The nature of LDLR gene
      mutations is different in various ethnicities and has also regional distribution
      within each ethnicity. Eleven mutations have already been described in the Greek
      population. This report describes seven LDLR gene mutations accounting for FH in
      Northwestern Greece (81T>G, 517T>C, 858C>A, 1285G>A, 1352T>C, 1646G>A and
      1775G>A) and their geographic distribution. We have recently described one of
      these mutations (1352T>C) as a novel point mutation in a Greek family originating
      from Northwestern Greece. Furthermore, two previously identified mutations
      (81T>C, 1775G>A) were also detected in the Greek FH patients for the first time.
      The 1775G>A mutation was responsible for all the homozygous patients in our area,
      indicating a founder effect. These data will favor the development of tailed
      information and screening programs in Northwestern Greece for the primary
      prevention of cardiovascular disease in FH patients.

PMID- 11317360
TI  - Rapid detection of the R408W and I65T mutations in phenylketonuria by glycosylase
      mediated polymorphism detection.
AB  - Mutation detection methods based upon chemical or enzymatic cleavage of DNA offer
      excellent detection efficiencies coupled with high throughput and low unit cost.
      We describe the application of the novel technique of Glycosylase Mediated
      Polymorphism Detection (GMPD) to the detection of two of the most common
      mutations of the PAH gene in the Irish population that cause phenylketonuria
      (PKU), R408W and I65T, which occur at relative frequencies of 41.0% and 10.4%
      respectively. GMPD assays for R408W and I65T were developed permitting
      fluorescent detection of cleavage products on the ALFexpresstrade mark automated
      DNA sequencer. The method was validated by screening a panel of PKU patients
      whose mutant genotypes had previously been characterised by standard methods. It
      also proved possible to perform multiplex detection of the two mutations by co
      electrophoresis of GMPD products. GMPD is a rapid and robust method for the
      detection of the R408W and I65T mutations, whose key advantage lies in its use of
      a pair of enzymes with high cleavage efficiency to detect a number of mutations
      as compared to the use of individual digestions with a range of specific
      restriction endonuclease enzymes. Hum Mutat 17:432, 2001.

PMID- 11317362
TI  - LDL receptor cDNA sequence analysis in familial hypercholesterolemia patients: 5
      novel mutations with high prevalence in families originating from southern Italy.
AB  - We screened a group of patients from southern Italy with clinically diagnosed
      familial hypercholesterolemia (FH) for mutations of the LDL receptor (LDLR) gene.
      RNA from each proband was analysed by RT-PCR followed by complete cDNA
      sequencing. Among 51 unrelated FH families we detected 17 mutations affecting the
      coding region of the LDLR gene. Five of these mutations, designated R395P,
      L783fsinsG, IVS15-3C>A, IVS3+5G>A, and 1698-1704delCACCCTAinsGCCCAAT (ITL545MPN),
      have not yet been reported in the literature. Interestingly, the novel IVS15-3C>A
      splicing mutation was detected in 20% of our unrelated FH families, suggesting an
      unusually high prevalence in our local population. Hum Mutat 17:433, 2001.

PMID- 11317364
TI  - Thirty-three novel COL1A1 and COL1A2 mutations in patients with osteogenesis
      imperfecta types I-IV.
AB  - Osteogenesis imperfecta (OI) is a heritable disease of bone characterized by low
      bone mass and bone fragility. Six different types of OI have been described to
      date, based on clinical phenotype and histological findings. The genetic defect
      in many patients with OI types I-IV is due to mutations in the genes encoding
      type I collagen, while patients with OI types V and VI show no evidence of
      mutations in the COL1A1/COL1A2 genes. Here we report thirty-three novel mutations
      in patients with types I-IV OI. Sixteen mutations were in COL1A1 and seventeen
      were in COL1A2. Most mutations resulted in substitutions for glycine: one of
      these, a doublet GG>CC transversion, created a unique Gly-->Pro missense mutation
      in the triple helical domain of COL1A2. Two rare triple helical Gly-->Glu
      substitutions in COL1A2 are also described. In addition, there were six single
      base deletion mutations resulting in frameshifts, seven splice junction
      mutations, and a 9-bp triple helix insertion associated with a severe (OI II)
      phenotype. The variety of mutations described in the COL1A1/COL1A2 genes giving
      rise to an OI phenotype is in accordance with the clinical heterogeneity of the
      disease. Hum Mutat 17:434, 2001.

PMID- 11317363
TI  - Novel coding-region polymorphisms in mitochondrial seryl-tRNA synthetase (SARSM)
      and mitoribosomal protein S12 (RPMS12) genes in DFNA4 autosomal dominant deafness
      families.
AB  - Two genes for components of the mitochondrial translational apparatus,
      mitochondrial seryl-tRNA synthetase (SARSM) and mitoribosomal protein S12
      (RPMS12) lie adjacent to one another on human chromosome 19, within the critical
      interval for the autosomal dominant deafness locus DFNA4. Both genes are
      plausible candidates for DFNA4, based on the fact that deafness mutations in
      mtDNA have been mapped both to tRNA-ser(UCN) and to the accuracy domain of the
      small subunit rRNA. We have sequenced the coding regions, proximal promoters, 5'
      and 3' UTR and splice junctional regions of both genes in two families with DFNA4
      linked deafness and in controls. Novel polymorphisms 84425C>T, 83907A>G,
      79485T>G, 79406C>T, 71755A>C and 68686C>G (numbered as in GenBank AC011455) were
      found in one or both families, but none is a plausible disease-causing mutation.
      Although regulatory mutations affecting either gene could still be involved in
      the phenotype, structural gene mutations affecting SARSM or RPMS12 can be
      excluded from consideration as the cause of DFNA4-linked deafness, at least in
      the families identified thus far.

PMID- 11317365
TI  - Nine novel APC mutations in Italian FAP patients.
AB  - Familial adenomatous polyposis (FAP) is a common hereditary syndrome
      characterized by early development of colorectal cancer consequent to extensive
      adenomatous polyps of the colon. In addition to the colonic manifestations the
      syndrome presents several extracolonic features including polyps of the upper
      gastrointestinal tract, congenital hypertrophy of the retinal pigment, jaw cysts,
      osteomata and desmoid tumors. In this study the entire APC coding region has been
      analysed for mutation in a panel of one Turcot and 33 unrelated Italian FAP
      patients using SSCP analysis, PTT and DNA sequencing. We detected APC mutations
      in 23 of them and identified nine which, to our knowledge were not previously
      reported. All of these novel mutations are in exon 15, including two nonsense
      mutations, 6 deletions or insertions leading to premature termination of the
      protein and one missense mutation (7697G>A). This last mutation occurs in the EB1
      binding domain of the APC protein and segregates in four relatives of the patient
      with three of them presenting 2-3 adenomatous polyps.

PMID- 11317366
TI  - Identification of four novel polymorphisms in the calcitonin/alpha-CGRP (CALCA)
      gene and an investigation of their possible associations with Parkinson disease,
      schizophrenia, and manic depression.
AB  - We identified novel polymorphisms in the calcitonin/CGRPalpha (CALCA) gene by
      direct sequencing of genomic DNA and subsequent genotyping by RFLP (restriction
      fragment length polymorphism) detection and investigated association with
      neurological or psychiatric disease. Four novel polymorphic alleles were found:
      two (g.979G>A and g.4218T>C) represented single nucleotide polymorphisms (SNPs),
      one consisted of two coupled SNPs in close vicinity to each other (g.1210T>C and
      g.1214C>G), and one was an intronic 16-bp microdeletion (2919-2934del16). One of
      the SNPs (g.4218T>C) causes a non-synonymous amino acid change (Leu66Pro) in the
      third exon, an exon common to both procalcitonin and pro-alpha-CGRP. In a
      subsequent association study, frequencies of the identified polymorphisms in
      Parkinson and schizophrenia patients were compared with frequencies in the normal
      population. No statistically significant association was found in our material.
      The 16-bp microdeletion polymorphism was present in a family with multiple cases
      of unipolar or bipolar depressive disorder. Using this polymorphism as marker,
      cosegregation with the phenotype was observed in the majority of individuals.

PMID- 11317367
TI  - RP1 in Chinese: Eight novel variants and evidence that truncation of the extreme
      C-terminal does not cause retinitis pigmentosa.
AB  - Heterozygous truncating mutations in the RP1 gene cause approximately 7% of
      autosomal dominant retinitis pigmentosa (RP) cases. To examine the role of RP1
      mutations in RP, we screened 101 unrelated Chinese RP patients (unselected for
      mode of inheritance) and 190 elderly normal control subjects for sequence changes
      in the coding exons for the 2156 amino acid RP1 protein. One patient had a
      mutation, thus RP1 mutations cause about 0.0% to 5.4% (95% confidence interval)
      of all RP among Chinese. The mutation was R677X, the most common found in
      Americans. Five other known sequence changes were found. In addition, nine novel
      sequence alterations were identified: 746G>A (R249H), 1437G>T (M479I), 2116G>C
      (G706R), 3024G>A (Q1008Q), 3188G>A (Q1063R), 5797C>T (R1933X), 6423A>G (I2141M),
      and the variants 6542C>T and 6676T>A, both in the 3' untranslated region. One
      control subject and three members of a non-RP family were heterozygous for
      R1933X, which is therefore likely to be a non-disease-causing variant. The most C
      terminal truncation previously reported was due to Tyr1053 (1-bp del) and
      occurred in RP patients. Thus the presence of a normal level of at least part of
      RP1 between amino acids 1052 and 1933 appears necessary to prevent RP. Hum Mutat
      17:436, 2001.

PMID- 11317368
TI  - A novel HEXA mutation [1393G>A (D465N)] in a Mexican Tay-Sachs disease patient.

PMID- 11317369
TI  - Five novel single nucleotide polymorphisms of the RB1 gene (g.5625T>C,
      g.70169T>G, g.76875A>T, g.78026delA, and g.150072T>C) in retinoblastoma patients.

PMID- 11317370
TI  - How much sophistication do we need?

PMID- 11317371
TI  - Effects of prism orientation on tensile strength of enamel.
AB  - PURPOSE: This study tested the hypothesis that the tensile strength of enamel
      varies according to prismatic orientation. MATERIALS AND METHODS: Eight
      extracted, caries-free human third molars were thoroughly cleaned with pumice and
      water. The entire enamel surface was conditioned with 37% phosphoric acid for 30
      s, air dried, and bonded with Single Bond adhesive system. Several layers of
      composite (Z-100) were incrementally applied to the crown to build up a "cube
      like" resin structure approximately 5 mm thick covering the entire crown of the
      teeth. The teeth were stored for 24 h in water at 37 degrees C, and then the
      crown was serially, vertically sectioned in a mesio-distal direction to obtain
      several slices approximately 0.7 mm thick. The slices were sectioned into halves,
      and each half was gently trimmed from both sides with a diamond bur to reduce the
      cross-sectional area to a "neck" located in enamel, either on the external slope
      or functional slope of the cusps. The specimens were trimmed to permit testing of
      enamel with its prisms either oriented parallel (PL) or perpendicular (PD) to the
      applied load. The trimmed specimens were glued to the fixtures of a Vitrodyne
      tester and stressed in tension at 0.5 mm/min. SEM images were taken from the
      fractured surfaces to examine the site of failure and confirm the prism
      orientation. RESULTS: Mean tensile strength of enamel was 24.7 +/- 9.6 MPa (n =
      22) for PL and 11.4 +/- 6.3 MPa (n = 22) for PD oriented enamel prisms (t value =
      -5.45, p < 0.05). There was no significant difference between specimens
      originating from different slopes of the cusps (p > 0.05). CONCLUSION: The
      results showed that tensile strength of enamel is dependent on the prismatic
      orientation.

PMID- 11317372
TI  - Field-emission scanning electron microscopy of resin-dentin interface morphology
      of seven dentin adhesive systems.
AB  - PURPOSE: The purpose of this study was to evaluate the resin-dentin interface
      morphology of 7 resin-based dentin adhesive systems (Solid Bond, EBS-Multi,
      PermaQuik, One Coat Bond, Gluma One Bond, Prime & Bond NT/NRC, and Clearfil Liner
      Bond 2V). MATERIALS AND METHODS: Fourteen dentin disks 1.0 mm thick were obtained
      from superficial occlusal dentin of extracted human third molars, and finished
      with wet 600-grit silicon carbide paper. Two dentin disks were bonded using each
      of the adhesives above according to the manufacturers' instructions, and a thin
      layer of flowable resin composite was applied. The specimens were kept in tap
      water for 24 h at 37 degrees C, and then assigned to one of two observational
      techniques: a fracture technique and an acid-base technique. Fracture technique:
      shallow grooves were cut, fixed in 10% buffered formalin, and dehydrated in an
      ascending ethanol series up to 100%, critical-point dried, and fractured along
      the prepared grooves. Acid-base technique: the specimens were embedded in epoxy
      resin, sectioned through the center, polished with diamond paste down to 0.25
      micron particle size, and treated with 10% orthophosphoric acid for 10 s and 5%
      sodium hypochlorite for 5 min. All the specimens were mounted on aluminum stubs,
      gold sputter coated, and observed using field-emission scanning electron
      microscopy (FE-SEM). RESULTS: All the dentin adhesive systems showed hybrid layer
      formation, but the thickness varied depending on the bonding system used. The
      self-etching priming systems (Prime & Bond NT/NRC and Clearfil Liner Bond 2V)
      showed the thinnest hybrid layer at 1 to 2 microns, whereas the "single-bottle"
      system (Gluma One Bond) exhibited the thickest hybrid layer at 8 to 16 microns.
      CONCLUSION: The ultramorphological structures of dentin bonding systems are
      determined by the composition of each system. Characterization of the interface
      of the adhesive system using the fracture technique provides additional
      information regarding the pattern of resin infiltration in some dentin bonding
      systems.

PMID- 11317373
TI  - Influence of collagen removal on shear bond strength of one-bottle adhesive
      systems in dentin.
AB  - PURPOSE: The aim of this study was to evaluate the influence of collagen removal
      on shear bond strength (SBS) of three hydrophilic one-bottle adhesive systems in
      dentin. MATERIALS AND METHODS: Test specimens were taken from one-hundred twenty
      bovine incisors. The specimens were debrided, polished with 320- to 600-grit
      Al2O3 paper, and randomly divided into 6 groups (n = 20): G1: acid/10% NaOCl +
      Bond 1 (B1H); G2: acid + Bond 1 applied according to manufacturer's instructions
      (B1); G3: acid/10% NaOCl + Optibond Solo (OSH); G4: acid + Optibond Solo used
      according to manufacturer's instructions (OS); G5: acid/10% NaOCl + Single Bond
      (SBH); G6: acid + Single Bond used according to manufacturer's instructions. In
      all groups, dentin was etched for 15 s, rinsed, and dried. In groups 1, 3, and 5,
      the 10% NaOCl was applied with a dwell time of 60 s, rinsed, and dried. In all
      groups, the adhesive systems were applied and light cured, and then a restorative
      composite resin (Z-100) was inserted in a teflon matrix and cured. The specimens
      were stored in humid conditions for 7 days at 37 degrees C. The SBS tests were
      performed in an EMIC universal testing machine with a crosshead speed of 0.5
      mm/min. The mean bond strengths in MPa (+/- SD) were analyzed with two-way ANOVA
      and Tukey's test (alpha = 0.05). RESULTS: The application of NaOCl significantly
      increased the SBS values of all systems except Optibond Solo. The means (SD) for
      adhesive systems with 10% NaOCl treatment were: SBH = 14.28 (4.21)a; B1H = 14.39
      (3.61)a; OSH = 10.35 (5.74)a; and values without 10% NaOCl were: SB = 10.35
      (2.95)a; B1 = 9.38 (3.10)a; OS = 9.79 (3.48)b. Different superscripts indicate
      significant difference. CONCLUSION: The removal of collagen increased the
      strength of dentin bonding, depending on the adhesive system used.

PMID- 11317374
TI  - Micromorphological investigation of noncarious cervical lesions treated with
      demineralizing agents.
AB  - PURPOSE: The purpose of this study was to examine the micromorphology of
      noncarious cervical lesions (NCCL) and the change occurring after acid
      conditioning. MATERIALS AND METHODS: Nine wedge-shaped lesions, 9 saucer-shaped
      lesions, and 5 third molars with prepared cervical cavities were used. All NCCLs
      exhibited a hard, smooth surface with no discoloration. The teeth were sectioned
      and divided into three groups, each containing the three lesion types. Teeth in
      Group I were not etched, and teeth in Groups II and III were etched with 35%
      phosphoric acid and 20% polyacrylic acid/3% aluminum chloride, respectively.
      Field emission SEM and atomic force microscopy were used to examine the lesion
      surfaces. RESULTS: The surfaces of the prepared cervical (control) lesions were
      covered with a smear layer. Treatment with phosphoric acid and polyacrylic acid
      resulted in removal of the smear layer, although some residual smear layer was
      found on the surface treated with polyacrylic acid. The images of the untreated
      surfaces of NCCL showed highly mineralized dentin with complete obliteration of
      the dentinal tubules. After treatment with phosphoric and polyacrylic acids, the
      images revealed demineralization of the surface, which was more pronounced on
      those treated with phosphoric acid. CONCLUSION: The mineral deposits on the
      surface of NCCL decreased the effect of acid conditioning. Although there was no
      apparent difference between the two forms of NCCL used in this study, further
      work is needed to better understand these lesions.

PMID- 11317375
TI  - Does pretreatment of cavities effectively promote good marginal adaptation of
      glass-ionomer cements?
AB  - PURPOSE: The aim of this laboratory study was to evaluate the marginal sealing
      ability of four glass-ionomer cements in cervical restorations (Class V) using
      dye penetration. Two conventional (C-GIC) and two resin-modified (RM-GIC) cements
      were used either with or without dentin conditioning with polyacrylic acid.
      MATERIALS AND METHODS: 96 cervical cavities of standardized size were prepared in
      vitro in the vestibular and lingual portions at the cementoenamel level of 48
      premolars. The coronal margins were prepared in enamel, the apical margins were
      localized in dentin. The 96 cavities were randomly divided into 4 groups of n =
      24 each. The cavities of each group were filled with one of the test materials,
      and only half of the cavities received a dentin conditioning for 20 s with
      polyacrylic acids before filling. The fillings were finished with a set of
      abrasive disks 24 h after setting. The restored teeth were stored in saline for 4
      weeks and subjected to dye penetration. The depth of dye penetration along the
      coronal and apical margin was measured on 4 longitudinal sections of each tooth
      with a semi-automatic image analysis system at 40x magnification. RESULTS: Mean
      depth of dye penetration ranged from 0 (ChemFil superior without conditioner) to
      0.13 mm (ChemFil superior with conditioner) at enamel sites, and from 0.02 (Fuji
      II LC with conditioner) to 0.74 mm (ChemFil superior with and without
      conditioner) at dentin sites. CONCLUSION: The conditioning of the cavities before
      filling improved the marginal adaptation significantly only in the Ketac-Fil
      group. Conventional glass-ionomer cements (C-GIC) in general demonstrated a lower
      sealing ability than the light-activated, resin-modified cements (RM-GIC). The
      adaptation of Photac-Fil quick is best without pretreatment--as recommended by
      the manufacturer.

PMID- 11317376
TI  - Influence of different acid conditioners on the tensile bond strength of 4
      META/MMA-TBB resin to Er:YAG laser-irradiated bovine dentin.
AB  - PURPOSE: This study evaluated the effect of acid conditioners on resin bonding to
      dentin following irradiation with an Er:YAG laser and investigated the
      characteristics of resin bonding to the laser-treated dentin. MATERIALS AND
      METHODS: Extracted bovine teeth were cervically sectioned to expose a dentin
      surface. After polishing, the dentin was irradiated with an Er:YAG laser. Aqueous
      solutions of 10% citric acid (10-0) or 10% citric acid/3% ferric chloride (10-3)
      were then applied to the laser-treated surface as acid conditioners. After the
      acid treatment, a PMMA rod was bonded to the irradiated dentin using 4-META/MMA
      TBB resin, and miniaturized dumbbell-shaped bonded specimens were prepared. These
      specimens were subjected to tensile testing, and fractured surfaces were observed
      with field-emission scanning electron microscopy (FE-SEM) to determine the mode
      of fracture. Additionally, the resin-dentin interfaces were observed under FE
      SEM. RESULTS: The tensile bond strength of acid-conditioned bonded specimens was
      lower than that of specimens not subjected to acid treatment (11.1 MPa) in the
      laser-irradiated group. No significant difference was observed between 10-0 and
      10-3 treatments. 10-3 treatment yielded the highest bond strength (24.6 MPa) in
      the nonirradiated group, as opposed to only 7.7 MPa in the laser-treated group.
      Cohesive failure in the dentin was observed in almost all specimens in the
      irradiated group. Furthermore, a 10- to 30-micron-thick resin-penetrated layer
      was observed at the interface between the dentin and resin. CONCLUSION: These
      results suggest that the effect of acid conditioners on resin bonding to dentin
      differs according to whether the dentin has been laser irradiated or not.

PMID- 11317377
TI  - Microtensile strength of composite bonded to hot-pressed ceramics.
AB  - PURPOSE: The objective of this in vitro study employing the microtensile test was
      to test the hypothesis that the tensile bond strength of hot-pressed ceramics to
      composite is controlled by the ceramic microstructure and the ceramic surface
      treatment. MATERIALS AND METHODS: Hot-pressed IPS Empress (E1) and IPS Empress 2
      (E2) ceramic blocks were polished with 1-micron alumina abrasive and treated as
      follows: group 1: 9.6% hydrofluoric acid (HF) on E1; group 2: 4% acidulated
      phosphate fluoride (APF) on E1; group 3: silane (S) on E1; group 4: HF + S on E1;
      group 5: APF + S on E1; group 6: HF on E2; group 7: APF on E2; group 8: S on E2;
      group 9: HF + S on E2; group 10: APF + S on E2. The surfaces as described above
      were then treated with Scotchbond Multi-Purpose Plus and covered with composite
      (Z-100). From the blocks obtained in this manner, specimens for microtensile
      testing were created by sectioning. Twenty bar specimens for each group were
      loaded to failure under tension using an Instron testing machine. RESULTS: Mean
      tensile bond strength (MPa) and standard deviation values are as follows: (1) 9.9
      +/- 1.2; (2) 0; (3) 27.2 +/- 4.8; (4) 20.6 +/- 3.0; (5) 13.6 +/- 4.5; (6) 41.7 +/
      6.7; (7) 19.1 +/- 2.6; (8) 30.1 +/- 5.3; (9) 56.1 +/- 4.1; (10) 36.9 +/- 3.9.
      All fractures occurred within the adhesion zone. SEM images of chemically etched
      specimens revealed that HF produced greater surface degradation and greater bond
      strength than APF for both E1 and E2 ceramics. The mean bond strength of groups 6
      through 10 (E2) was significantly greater than that of groups 1 through 5 (E1)
      for each treatment condition. CONCLUSION: The tensile fracture resistance of the
      composite-ceramic adhesion zones is controlled primarily by ceramic
      microstructure and ceramic surface treatment.

PMID- 11317378
TI  - The effect of secondary curing of resin composite on the adherence of resin
      cement.
AB  - PURPOSE: The aim of this study was to measure the adherence between a resin
      cement and a resin composite polymerized with and without an additional secondary
      cure of the resin composite. MATERIALS AND METHODS: The resin cement was 3M Opal
      Luting Composite and the resin composite was Z-100. The resin composite was
      either polymerized by light only, or given an additional secondary cure at 110
      degrees C for 10 min. For each curing mode, the composite was either ground on
      carborundum paper #1000 or sandblasted with alumina powder. The adherence was
      determined as bond strength and as bond energy. RESULTS: Without sandblasting of
      the resin composite, the heat treatment resulted in reduced adherence both in the
      bond strength and the bond energy mode of measurement. With sandblasting, only
      the bond energy was reduced as a consequence of the heat treatment. CONCLUSION:
      On the basis of the experiments conducted, it may be concluded that secondary
      cure of resin composites takes place at the expense of the adherence to the resin
      cement.

PMID- 11317379
TI  - A clinical evaluation of Class II composites placed using a decoupling technique.
AB  - PURPOSE: This study was undertaken to evaluate the three-year clinical
      performance of Class II restorations of a fine particle hybrid composite placed
      using a decoupling placement technique, whereby polymerization shrinkage stresses
      at the cervical tooth-restoration interface were minimized by separating the
      initial gingival increment of composite from the body of the restoration using a
      polyurethane varnish. MATERIALS AND METHODS: The study was a practice-based
      explanatory, single-center clinical trial. A minimum of 40 Class II restorations
      of the material under investigation (Tetric) was required to be placed in
      predominantly molar teeth in selected patients. The restorations were placed
      using a decoupling incremental technique, bonding being accomplished using Syntac
      and Heliobond. The restorations were reviewed within 1 month of placement,
      thereafter at 18 months, then at 2 and 3 to 4 years using predetermined codes and
      criteria. Impressions and photographic records were used to obtain retrospective,
      third-party assessments of the restorations. RESULTS: Of 43 restorations
      originally placed and found to have ideal characteristics at baseline review, 41
      (95%) were reviewed at 18 months, 36 (84%) at two years, and 31 (74%) at 3 to 4
      years. None of the restorations were found to have suffered significant
      deterioration, notwithstanding three restorations having been lost to the study
      because of the replacement of part of the restored tooth for causes other than
      the catastrophic failure of the material. No secondary caries or postoperative
      sensitivity was recorded. CONCLUSION: It was concluded that the findings support
      the use of the material under investigation in the restoration of moderate- to
      large-sized Class II preparations in selected patients. The decoupling placement
      technique employed may be found to be an effective means to limit postoperative
      sensitivity and to contribute to the favorable in-service performance of
      restorations of the type investigated. Good practice would now require a
      multicentered, randomized controlled trial to investigate the effectiveness of
      the material and, in particular, the decoupling technique under the conditions of
      everyday practice.

PMID- 11317380
TI  - Posterior restorations--a clinical view.
AB  - This paper examines the state-of-the-art in the direct restoration of posterior
      teeth. The existing paradigms for the management of caries are questioned and
      some existing methods of cavity preparation are reviewed. Dental restorations
      need to be durable but able to adapt to a changing environment brought about by
      wear of the adjacent tooth substance and by fatigue processes within the tooth
      itself. The wear of restorative materials needs to be matched to that of the
      tooth, otherwise differential loss of either the restorative material or the
      enamel may destabilize the occlusion. Esthetic instability due to natural
      darkening of the tooth with age, punctuated by clinical intervention with
      bleaching procedures, adds a further dimension to the concept of a permanent
      restoration. Clinical methods that minimize the disruptive effects of dental
      restorations upon the remaining tooth structure are a continuing challenge.

PMID- 11317382
TI  - The cycle of progress.

PMID- 11317381
TI  - Minimally invasive operative care. II. Contemporary techniques and materials: an
      overview.
AB  - SUMMARY: Restorative dentistry has experienced a shift from the mainly reparative
      dentistry of the 20th century towards a minimal intervention approach.
      Contemporary operative treatment incorporates the MI philosophy in cavity design.
      Currently available techniques to pursue minimally invasive restorative
      treatments are highlighted. Characteristics of adhesive materials that facilitate
      minimally invasive operative care are discussed. CONCLUSION: When operative
      intervention is the designated treatment for initial caries, currently available
      operative techniques and contemporary materials warrant a minimally invasive
      approach. Minimal intervention applied to the operative field keeps the options
      open for long-term preservation of the restored tooth.

PMID- 11317383
TI  - Improving cervical restorations: a review of materials and techniques.
AB  - INTRODUCTION: There is a great variety of cervical lesions and an increased need
      for treatment because patients complain either about esthetics, hypersensitivity,
      or even food impaction. The cumulative effects of noncarious dental tissue loss
      are increasingly evident within any population. The prevalence of these
      noncarious lesions has been estimated at between 31% and 56%, with 85% of the
      population showing some loss of tooth structure in the cervical area. Since more
      elderly patients will keep their teeth for a longer time, the problems regarding
      the cervical areas of the teeth will increase. Therefore, the challenge for the
      dentist is rather substantial, since it has been shown that the longevity of
      these cervical restorations is not as great as that of other restorations. The
      purpose of this review is to summarize some facts about cervical lesions, the
      different tooth-colored restorative materials and their application, and the
      assessment of the clinical performance of these materials.

PMID- 11317384
TI  - Longevity of restorations in posterior teeth and reasons for failure.
AB  - PURPOSE: This article compiles a survey on the longevity of restorations in
      stress-bearing posterior cavities and assesses possible reasons for failure.
      MATERIALS AND METHODS: The dental literature predominantly of the last decade was
      reviewed for longitudinal, controlled clinical studies and retrospective cross
      sectional studies of posterior restorations. Only studies investigating the
      clinical performance of restorations in permanent teeth were included. Longevity
      and annual failure rates of amalgam, direct composite restorations, glass
      ionomers and derivative products, composite and ceramic inlays, and cast gold
      restorations were determined for Class I and II cavities. RESULTS: Annual failure
      rates in posterior stress-bearing restorations are: 0% to 7% for amalgam
      restorations, 0% to 9% for direct composites, 1.4% to 14.4% for glass ionomers
      and derivatives, 0% to 11.8% for composite inlays, 0% to 7.5% for ceramic
      restorations, 0% to 4.4% for CAD/CAM ceramic restorations, and 0% to 5.9% for
      cast gold inlays and onlays. CONCLUSION: Longevity of dental restorations is
      dependent upon many different factors that are related to materials, the patient,
      and the dentist. The principal reasons for failure were secondary caries,
      fracture, marginal deficiencies, wear, and postoperative sensitivity. A
      distinction must be made between factors causing early failures and those that
      are responsible for restoration loss after several years of service.

PMID- 11317385
TI  - Durability of new restorative materials in Class III cavities.
AB  - PURPOSE: The aim of this study was to evaluate the durability of new hybrid tooth
      colored restorative materials in Class III cavities. MATERIALS AND METHODS: 154
      large-sized Class III restorations were placed in 50 patients. The patients
      received one of each of the three following materials: a resin composite (RC,
      Pekafill), a polyacid-modified resin composite (PMRC, Dyract) (compomer), and a
      resin-modified glass-ionomer cement (RMGIC, Fuji II LC). The restorations were
      evaluated yearly with slightly modified USPHS criteria. RESULTS: Of 141
      restorations evaluated at 6 years, 16 were estimated as unacceptable. Seven of
      these were replaced: 2 fractures, 3 recurrent caries, and 2 due to unacceptable
      color match. In 9 other restorations with unacceptable color match, the patients
      did not request replacements. No significant differences were seen between the
      materials concerning the occurrence of recurrent caries. The RC showed
      significantly better color match. Significantly higher surface roughness was seen
      for the aged RMGIC restorations. Fracture of the incisal enamel corner was
      observed contiguous to ten restorations in the 6-year evaluation. None of the
      restorative techniques resulted in postoperative sensitivity or loss of vitality.
      CONCLUSION: The resin composite showed the best durability.

PMID- 11317386
TI  - Minimally invasive operative care. I. Minimal intervention and concepts for
      minimally invasive cavity preparations.
AB  - SUMMARY: From the mainly reparative dentistry of the 20th century, contemporary
      dentistry shifts towards a minimal intervention (MI) approach encompassing up-to
      date caries diagnosis and risk assessment before arriving at a treatment
      decision. An overview is provided of incorporating MI philosophy into the field
      of operative dentistry. The ultimate goal of MI is to extend the lifetime of
      restored teeth with as little intervention as possible. When operative care is
      indicated, it should be aimed at "prevention of extension." Black's principles
      for cavity design are considered and put in the perspective of minimally invasive
      operative care. Guiding principles for contemporary adhesive cavities are
      reviewed. CONCLUSION: Contemporary operative care should be based on a minimally
      invasive approach. Minimal intervention is not just a technique, it is a
      philosophy!

PMID- 11317387
TI  - Layering concepts in anterior composite restorations.
AB  - SUMMARY: With increasing patient demands for esthetic dentition, composite resin
      restorations enjoy great popularity due to excellent esthetics, acceptable
      longevity, and relatively low costs. Shading concepts used by manufacturers,
      however, may be confusing to many clinicians. PURPOSE: To review and describe the
      current main shading concepts, evaluate their potential for creating natural
      esthetics, and provide guidelines for application.

PMID- 11317388
TI  - Extended indications for directly bonded composite restorations: a clinician's
      view.
AB  - Adhesive techniques play an important role in almost every discipline of
      dentistry. Compared to conventional direct and indirect techniques, the direct
      adhesively bonded composite restoration offers many advantages. This article
      summarizes and illustrates some of them.

PMID- 11317389
TI  - Indirect posterior restorations using a new chairside microhybrid resin composite
      system.
AB  - A plethora of choices is available as potential tooth-colored restoratives for
      the posterior dentition. Advances in adhesive technology and esthetic chairside
      microhybrid composite resins have permitted clinicians to perform inlay/onlay
      restorations. The use of adhesive indirect procedures offers advantages such as
      better control of polymerization shrinkage and anatomical form, when compared to
      conventional, direct restorative techniques. This article describes the use of a
      new chairside microhybrid composite system as an indirect restorative material,
      using semidirect and indirect techniques that can be accomplished within the
      realm of a dental operatory.

PMID- 11317390
TI  - Light-curing units, polymerization, and clinical implications.
AB  - A comprehensive review of the techniques of light initiation of dental composites
      with special attention to polymerization efficacy and shrinkage stress control is
      presented. Optimal setting of an average-sized composite restoration requires a
      certain quantity of light energy. The amount of energy depends on the
      characteristics of the light source used and the time of irradiation. Swift
      conversion with high-energy lamps is proportionally accompanied by rapid
      hardening and could negatively affect the marginal integrity of the adhesive
      restoration. However, preliminary stress measurements did not show an increase in
      the rate of stress development. Full conversion in the deeper areas of the
      restoration may not be possible if defects occur in one or more of the various
      lamp components. Prolonging the irradiation time could reduce this risk. A
      regular check on the energy output of the light source is recommended. Although
      the high-energy light sources with their extremely short irradiation times should
      be used in a more critical way than the conventional light sources, they save a
      considerable amount of time and facilitate bond application, leading to better
      restorations where isolation control need not be optimal.

PMID- 11317391
TI  - Mechanical disruption of dentin collagen fibrils during resin-dentin bond
      testing.
AB  - PURPOSE: To determine if collagen fibrils on the dentin side of failed resin
      dentin interfaces undergo mechanical disruption during microtensile bond testing.
      MATERIALS AND METHODS: Extracted, caries-free human third molars were divided
      into four groups. The occlusal enamel was removed, leaving a flat dentin surface
      for bonding. Resin composite buildups were made after the acid-conditioned dentin
      was bonded with either Single Bond (S) or One-Step (O), and using either moist
      bonding (M) or air drying for 5 s (D). After storage in water for 24 h, the teeth
      were vertically sectioned into an array of 0.9 x 0.9 mm resin composite-dentin
      beams. They were stressed to failure using the nontrimming version of the
      microtensile bond test. Fractured dentin and resin composite sides of
      representative beams from each group that exhibited adhesive failures under light
      microscopy examination were prepared for scanning (SEM) and transmission electron
      microscopy (TEM). RESULTS: A two-way ANOVA showed that moist bond strengths were
      significantly higher than those made to dry dentin (M > D; p < 0.001), but that
      there was no difference between the adhesives (S vs O; p = 0.547). SEM analysis
      showed the presence of loose collagen fibrils within fractured hybrid layers in
      the dry groups, but not in the moist groups. TEM examination of the dry-bonded
      groups revealed collagen fibrils that were thinner and exhibited abnormally wide
      interfibrillar spaces when hybrid layers were intact. Within dry-bonded fractured
      hybrid layers, broad mechanical disruption zones could be seen, consisting of
      fibrils that were devoid of cross banding, defibrillation of the subfibrillar
      architecture, and gross disaggregation into microfibrils. In the moist-bonded
      groups, only short mechanical disruption zones were found along the torn edges of
      the collagen fibrils. The rest of the fibrils beyond the fracture site were
      intact and retained their periodicity. Mechanical testing of demineralized
      matrices yielded a maximum modulus of elasticity of 43.9 +/- 6.1 MPa. CONCLUSION:
      We speculate that adhesive resin has a protective function for demineralized
      collagen in well-infiltrated hybrid layers. We propose that both the collagen and
      resin contribute to load sharing during stress application until the final moment
      of rupture. On the other hand, collagen fibrils in poorly infiltrated hybrid
      layers, being unsupported by resin, undergo various degrees of irreversible
      mechanical disruption depending on how the stress is dissipated. The collagen
      fibril network has a much lower modulus of elasticity compared to those of resin
      infiltrated fibrils or the demineralized dentin.

PMID- 11317392
TI  - Long-term mechanical properties of EDTA-demineralized dentin matrix.
AB  - PURPOSE: To determine the long-term ultimate tensile strength (UTS) and modulus
      of elasticity (E) of EDTA-demineralized human dentin after storage in PBS
      (phosphate buffered saline) for up to 48 months. MATERIALS AND METHODS: Dentin
      beams measuring 0.7 x 0.7 x 8.0 mm were prepared from the crowns of extracted
      human third molars. The ends of the beams were covered with resin composite and
      demineralized for 6 days in 0.5 mol/L EDTA (pH = 7.0). Demineralized control
      specimens were subjected to tensile testing at 0.5 mm/min after 24 hours of
      immersion in PBS solution. Experimental specimens were stored in PBS at room
      temperature (25 degrees C) and tested after 18 and 48 months. The maximum load at
      failure and the load/displacement curves were used to calculate the UTS as a
      function of the cross-sectional area and E, respectively. The results were
      analyzed by ANOVA and Student Neuman Keuls tests. TEM micrographs were obtained
      from the control specimens and from those that were stored and tested after 48
      months. RESULTS: No significant changes in either UTS or E were observed in the
      specimens after long-term storage. The 48-month values were not statistically
      significantly different from the values obtained at 24 hours (p > 0.05). TEM
      images revealed a normal, intact structure of the collagen fibrils with no signs
      of degradation or denaturation. CONCLUSION: Long-term storage of EDTA
      demineralized human dentin in PBS solution did not cause any significant
      reduction of its mechanical properties. The structure of the collagen fibrils as
      observed by TEM appeared normal and did not seem affected by long-term storage.

PMID- 11317393
TI  - Ability of adhesive systems to seal dentin surfaces: an in vitro study.
AB  - PURPOSE: The objective of this study was to evaluate the ability of three
      adhesive systems to seal dentin by measuring the permeability of dentin before
      and after bonding procedures. MATERIALS AND METHODS: Thirty-six flat dentin
      surfaces were prepared from human extracted teeth and connected to a fluid-filled
      system for permeability measurements. The hydraulic conductance of the flat
      occlusal surface of dentin was measured by the filtration technique, before and
      after application of ScotchBond MP Plus, Prime & Bond 2.0, and All-Bond 2.
      Bonding procedures were followed by P-50 resin composite application. The
      specimens were then perfused with silver nitrate to permit morphologic
      localization of microleakage pathways using SEM. RESULTS: The results showed that
      the best dentin seal was produced by All-Bond 2, followed by Prime & Bond 2.0,
      and ScotchBond MP Plus. However, none of the three bonding systems tested was
      able to totally prevent the passage of fluid across the dentin in every specimen.
      When observed with SEM, each adhesive system exhibited different patterns of
      leakage. CONCLUSION: The inability of all three materials to create a perfect
      seal in vitro raises concerns about the ability of these adhesive systems to
      provide completely sealed restorations in vivo. However, because the current
      study applied pressure 3 to 6 times higher than physiologically normal, it is
      likely that the leakage represents a worst-case scenario.

PMID- 11317394
TI  - Influence of different dentinal substrates on the tensile bond strength of three
      adhesive systems.
AB  - PURPOSE: To evaluate the influence of the method and duration of storage for
      different types of teeth prior to their use in dentin bonding tests with three
      adhesive systems. MATERIALS AND METHODS: Recently extracted sound human molars,
      bovine incisors, and human caries-free molars obtained from exhumed bones 5 years
      postmortem were used. The latter group of teeth was kept dry for 6 months, and
      then rehydrated in distilled water over a period of 30 days. The adhesive systems
      used were Prime&Bond 2.1. Single Bond, and Etch&Prime 3.0. Human teeth were
      embedded longitudinally in PVC cylinders; bovine incisors were embedded leaving
      the buccal surface exposed. Flat dentin surfaces were cut with a diamond disk and
      ground with up to 600-grit SiC paper. Adhesives were applied following
      manufacturers' instructions. A silicone mold with a cone-shaped perforation (4.5
      mm high and 2 mm diameter at the smallest) was fixed on the dentin surface and
      filled with TPH composite resin. The specimens were stored in distilled water for
      two weeks before testing. RESULTS: ANOVA did not detect statistical differences
      either in the main factors (substrate and adhesive system) or in their
      interaction (p > 0.05). Tensile bond strength averages ranged from 11.6 to 14.2
      MPa. The dentinal substrates showed similar performances, regardless of the
      adhesives tested. CONCLUSION: The differences among the three dentin substrates
      do not appear to be critical for the tensile bond strength test for the three
      adhesive systems. The adhesive systems presented similar bond strengths.

PMID- 11317395
TI  - In vitro study of enamel and dentin marginal integrity of composite and compomer
      restorations placed in primary teeth after diamond or Er:YAG laser cavity
      preparation.
AB  - PURPOSE: The aim of this in vitro study was to evaluate the effect of laser vs
      diamond instruments on Class II and Class V cavity margins in primary teeth with
      SEM after restoration with composite and compomer materials and subsequent
      thermocycling. MATERIALS AND METHODS: Class V cavities with margins completely
      located in enamel were prepared in 36 extracted primary teeth to examine the
      restoration-enamel interface. Eighteen cavities were prepared with an Er:YAG
      laser operated at 3 Hz, 300 mJ/pulse, and 18 with a spherical fine diamond bur.
      In 24 primary teeth, Class II cavities with cervical proximal margins located in
      dentin were prepared for examination of the restoration-dentin interface. All
      Class II cavities were prepared with a conventional cylindrical diamond bur. In
      12 cavities, the margins located in dentin were conditioned with an Er:YAG laser
      (1 Hz, 100 mJ/pulse). All cavities were restored with a fine hybrid composite
      resin or a compomer material. RESULTS: SEM examination of Class V cavities after
      thermocycling (between 5 degrees C and 55 degrees C, 2500 cycles) revealed over
      90% "perfect" margins in all composite fillings and in those compomer
      restorations applied after conventional preparation and acid etching. Compomer
      restorations placed without acid etching revealed a significantly superior
      marginal integrity in laser-prepared cavities (81% perfect margins) vs
      conventionally prepared cavities (60% perfect margins). SEM analysis of the
      dentinal margins of both compomer and composite restorations in Class II cavities
      showed mean percentages of perfect marginal adaptation ranging from only 13% to
      66%. CONCLUSION: Er:YAG laser treatment can be recommended for composite
      restorations in Class V cavities in primary teeth. Compomer restorations can be
      placed after conventional preparation of Class V cavities and acid etching or
      after laser preparation. Dentin bonding in Class II cavities in primary teeth is
      not sufficient and cannot be improved with Er:YAG laser pretreatment.

PMID- 11317396
TI  - Marginal microleakage in bonded amalgam restorations: a combined in vivo and in
      vitro study.
AB  - PURPOSE: This study evaluated the marginal microleakage in bonded amalgam
      restorations in teeth extracted a month after restoration placement. MATERIALS
      AND METHODS: Nine teeth in a patient scheduled for complete extraction were
      selected. In each tooth, a buccal prepared cavity was treated with Scotchbond
      Plus and filled with high copper amalgam. In four teeth, a lingual unlined
      restoration was also prepared as control. A month later, all the teeth were
      extracted; seven teeth were immersed for 48 hours in a 0.05% basic fucsine dye
      solution and then sectioned. Sections were observed with a stereomicroscope at
      10X. Results were statistically evaluated using a nonparametric Mann-Whitney test
      for independent data. The remaining two teeth were sectioned and observed using a
      scanning electron microscope (SEM). RESULTS: Stereomicroscopic analysis revealed
      that 80% of bonded specimens did not exhibit dye infiltration at the enamel
      margin; the same percentage of bonded specimens showed partial infiltration at
      the cervical margin. In the unlined control specimens, there was a complete dye
      infiltration at both margins. SEM analysis revealed a good adaptation between
      resin and tooth and between resin and amalgam. CONCLUSION: Bonded amalgam
      restorations are effective in reducing marginal microleakage, particularly at the
      enamel margin.

PMID- 11317397
TI  - Longevity of oroincisal ceramic veneers on canines--a retrospective study.
AB  - PURPOSE: The longevity of oroincisal veneers on canines of IPS-Empress ceramic
      for the restoration of lost canine guidance was determined in a retrospective
      study. MATERIALS AND METHODS: Since 1992, all ceramic restorations made in the
      Department of Operative Dentistry have been entered in a data base. In that time
      period, 17 patients with 36 oroincisal veneers on canines to restore lost canine
      guidance have been documented. The survival rate of the restorations was
      calculated with the Kaplan-Meier method. RESULTS: The mean follow-up period was
      6.74 years. The 6.5-year survival rate was 76%. The 6.5-year survival rate of
      canine oroincisal ceramic veneers in the maxilla was 74%, and in the mandible
      78%. The difference in the survival rate of maxillary and mandibular restorations
      was not statistically significant. In the follow-up period, 8 of the 36 IPS
      Empress canine veneers failed. Reasons for failure were ceramic fracture,
      fracture of the adhesive bond, and loss of function. CONCLUSION: In view of the
      longevity, the excellent properties of the IPS-Empress ceramic material, i.e.,
      minimum abrasion of the opposing teeth, and good esthetics, we consider the
      restoration of lost canine guidance using this technique a viable alternative to
      the classical precious-metal pinledge or composite buildup.

PMID- 11317398
TI  - A simple method to protect patient and environment when using sandblasting for
      intraoral repair.
AB  - Repair or correction of intraoral restorations can be an alternative to complete
      replacement. A simple sandblasting device is very effective in producing a
      microretentive surface on every restorative material. A disadvantage of the
      technique is the production of an aerosol contaminated with the small, abrasive
      aluminum-oxide particles. In this article, a simple solution is given to protect
      the patient and environment against this dust during intraoral reparatory
      procedures involving sandblasting.

PMID- 11317399
TI  - Analysis of sealing vs tensile bond strength of eight adhesive restorative
      material systems.
AB  - PURPOSE: Using a simulated perfusion system, the intent was to determine: 1) the
      sealing ability of eight restorative materials (five composite resins and three
      compomers) used together with their corresponding dentin bonding systems, 2)
      their tensile bond strength, and 3) the correlation (if any) between both
      parameters. MATERIALS AND METHODS: Permeability in crown segments from sound
      human third molars (n = 140) subjected to simulated perfusion (32 cm of distilled
      water) was measured before and after restoring with each material, and the
      percentage of decrease in permeability (PPD) was recorded. Specimens were later
      subjected to tensile tests to determine the tensile bond strength (TBS) of the
      interface. Finally, parameters were analyzed for correlation. RESULTS: For the
      eight adhesive systems, the percentage of reduction in permeability was
      relatively high [mean in %, (SD)]: F2000 93.6 (5.7), SB1 88.6 (11.3), SSC 86.0
      (5.7), PB20 81.1 (15.9), COM 77.5 (10.8), OPTS 75.3 (20.6), DYR 73.7 (12.7), SSPR
      65.5 (19.8). TBS values were relatively low [mean (SD)], in MPa: F2000 1.8 (0.7),
      SB1 4.9 (1.4), SSC 2.6 (1.4), PB20 4.3 (1.2), COM 2.4 (1.1), OPTS 4.5 (1.7), DYR
      1.6 (0.6), SSPR 4.2 (1.5). We could not demonstrate any statistically significant
      correlation between both parameters for these results (maximum significance
      [F2000]: r = 0.39, p = 0.206). CONCLUSION: No material completely ceased to
      filtrate through the interface. The low TBS values were probably due to the large
      size of adhesive areas. No significant correlation was found between PPD and TBS
      for the materials tested. There was a statistically significant relationship (r2
      = 0.063, p = 0.018) between TBS and TBA (total bonded area), described by the
      equation TBS = 5.9 - 0.03.TBA.

PMID- 11317400
TI  - Marginal characteristics of different filling materials and filling methods with
      standardized cavity preparation.
AB  - PURPOSE: The aim of the present study was to investigate the influence of
      different filling materials and methods on marginal integrity in Black Class I
      fillings. MATERIALS AND METHODS: Standardized occlusal cavities were prepared in
      80 extracted human molars. The preparations were filled with composite resin (1),
      with composite resin using the incremental technique (2), an experimental glass
      fiber-reinforced (3) and polyester-reinforced (4) composite resin, a direct
      composite inlay (5), a ceramic insert (6), a Cerafil inlay (7), and with an
      experimental direct filling using Dyract AP compomer (8). Allocation of the teeth
      to the test groups was randomized; further processing was done on a blind basis.
      After the preparation of replicas, the teeth were subjected to a thermomechanical
      cycling process of 2,000 temperature cycles (5 degrees C/55 degrees C) and 50,000
      stress cycles (50 N). This was followed by production of a second set of replicas
      and quantitative margin analysis by SEM (200X). A dye penetration test was then
      performed on the mesiodistal section. RESULTS: Groups 1, 2, 5, 6 and 7 displayed
      a good primary marginal quality, with the proportion of continuous margins
      reaching more than 85%. Significantly poorer results were recorded for the
      experimental glass-fiber-reinforced composite resins and Dyract compomer, where
      the proportion of perfect margins was only between 36% and 73%. In groups 1, 2,
      5, 6 and 7, marginal integrity remained stable after the thermomechanical stress
      cycles, with the Cerafil inlays recording the best values: 89% perfect margins
      and 3% marginal gaps. In contrast, the experimental composite resins and the
      compomer underwent a significant (p < 0.05) increase in the proportion of
      marginal gaps and a significant (p < 0.05) reduction in the proportion of
      continuous margin. CONCLUSION: The results of this study show that neither Dyract
      compomer nor the glass-fiber-reinforced composite resins tested can be
      recommended for use in the occlusally stressed posterior region, whereas the
      other filling materials and methods were sufficiently stress resistant.

PMID- 11317401
TI  - Long-term resin bond strength to zirconia ceramic.
AB  - PURPOSE: The aim of this in vitro study was to evaluate the long-term bond
      strength of adhesive bonding systems to yttrium-oxide-partially-stabilized
      zirconia ceramic (YPSZ). MATERIALS AND METHODS: Plexiglas tubes filled with resin
      composite were bonded to industrially manufactured zirconia ceramic disks (96%
      ZrO2 stabilized by 4% Y2O3). After air abrading the ceramic and ultrasonic
      cleansing, groups of 16 samples were bonded in an alignment apparatus using 7
      different bonding methods. Subgroups of 8 bonded samples were tested for tensile
      strength following storage in distilled water at 37 degrees C either for 3 days
      or 2 years. In addition, the 2-year samples were thermocycled 37,500 times. The
      statistical analyses were conducted with the Kruskal-Wallis test followed by
      multiple pair-wise comparison of the groups using the Wilcoxon rank sum test.
      RESULTS: A moderate to relatively high initial bond strength was achieved by air
      abrasion alone, the additional use of a silane, or acrylizing the YPSZ surface in
      combination with a conventional bis-GMA resin composite. However, these methods
      failed spontaneously over storage time. The use of the bis-GMA resin composite
      after tribochemical silica coating of YPSZ and the use of a polyacid-modified
      resin composite after air abrasion of YPSZ resulted in a high initial bond
      strength which decreased significantly over storage time. A durable resin bond
      strength to YPSZ was achieved only after air abrasion of YPSZ and using one of
      two resin composites containing a special phosphate monomer. CONCLUSION: A
      durable bond strength to YPSZ was achieved only by using resin composites
      containing a special adhesive monomer.

PMID- 11317402
TI  - Criteria for disposable brush tips for use in dentistry.
AB  - PURPOSE: The purpose of this paper is to document criteria considered appropriate
      for disposable brush tips used to apply agents in liquid and gel form and to
      carry out an assessment of examples of brush tips supplied by manufacturers of
      dental materials. MATERIALS AND METHODS: Three brush tips were selected at random
      from sixteen packs of dental materials and one dedicated pack of brushes, and
      examined under 4X magnification. The brush tips were assessed with regard to
      criteria such as cost, flexibility, shape, size, etc to determine, in particular,
      whether any correlation existed between brush tip characteristics and the type
      (i.e., fluid or gel) and thickness of agent to be applied. RESULTS: When assessed
      with regard to the ideal criteria, no correlation was apparent between brush tip
      features and the type and thickness of agent to be applied. CONCLUSION: It is
      suggested that brush tip effectiveness may be found to be dependent upon the
      correct choice of tip shape, length, and size for each particular function, and
      that operators and manufacturers alike should choose the brush tip considered
      most suitable for any given application. Before application of a given material,
      clinicians should select the brush tip to be used to ensure that the appropriate
      amount of material will be applied in the intended thickness.

PMID- 11317403
TI  - The cost of saving time.

PMID- 11317404
TI  - An ultrastructural study of the influence of acidity of self-etching primers and
      smear layer thickness on bonding to intact dentin.
AB  - PURPOSE: The objectives of this study were (1) to determine the depth of
      demineralization into intact dentin using several self-etching primer systems
      with different pH values, and (2) to evaluate whether hybridization of intact
      dentin in Clearfil SE Bond may be affected by variation in the thickness of the
      smear layers. MATERIALS AND METHODS: Dentin disks were created from mid-coronal
      dentin in extracted, human third molars. Three self-etching primer systems
      (Clearfil Liner Bond II, Liner Bond 2V, and SE Bond) were applied separately to
      these disks to evaluate how deep self-etching systems penetrate through smear
      layers into intact dentin. Dentin treated with All-Bond 2 using the "no-etch"
      technique was used as a control group. In the second part of the study, dentin
      disks with different smear-layer thicknesses were produced. The cryofractured
      control group was devoid of a smear layer. The experimental teeth were ground
      with 60-, 180-, or 600-grit SiC paper and bonded using SE Bond. Dentin disks were
      bonded together and examined with TEM. RESULTS: All-Bond 2 did not etch beyond
      the smear layer. The three self-etching primers etched beyond the smear layer to
      form true hybrid layers within intact dentin. This layer was thickest with Liner
      Bond 2 (ca 1.2 to 1.4 microns), but very thin (0.5 micron) using both Liner Bond
      2V and SE Bond. Application of SE Bond to dentin of different surface roughness
      produced hybridized smear layers of variable thickness. However, the thickness of
      the underlying true hybrid remained consistent for the four groups (ca 0.4 to 0.5
      micron). CONCLUSION: Self-etching primers create thin hybrid layers that
      incorporate the smear layer. The suspicion that thick smear layers may interfere
      with the diffusion of self-etching primers into the underlying intact dentin was
      not confirmed.

PMID- 11317405
TI  - Effect of smear layers on the bonding of a self-etching primer to dentin.
AB  - PURPOSE: The objective of this work was to evaluate the effect of the absence and
      presence of smear layers on bonds made to dentin using a self-etching primer
      system, Clearfil SE Bond. MATERIALS AND METHODS: Dentin surfaces with different
      smear layer thickness were created from mid-coronal sound dentin in extracted,
      human third molars. The control group was cryofractured to create a bonding
      surface that was devoid of a smear layer. The experimental teeth were ground with
      wet 60-, 180- or 600-grit SiC paper. They were bonded using SE Bond, followed by
      resin composite buildups. After 1 day, bonded specimens were sectioned into
      multiple 1- x 1-mm beams. Microtensile bond strengths were determined and the
      results analyzed with ANOVA and the Student Neuman Keuls test. Fractographic
      study of cross sections of failed interfaces from the dentin side of
      representative beams was performed using both SEM and TEM. RESULTS: SE Bond
      produced high bond strengths (ca 50 MPa) to both smear layer-free and smear layer
      covered dentin. SEM examination was inadequate to define the exact nature of
      interfacial failures. TEM observations demonstrated a thin (ca 400 to 500 nm)
      hybrid layer in the fractured dentin and thicker (ca 1 to 4 microns) hybrid
      layers on smear layer-covered dentin. This included a thick, hybridized smear
      layer and a thin, underlying true hybrid layer in the intact dentin. Separation
      of the two hybrid layers was not evident in interfacial failures. CONCLUSION:
      Self-etching primers create thin hybrid layers that incorporate the smear layer.
      This study shows that formation of true hybrid layers occurs irrespective of
      smear layer thickness and that both hybrid layers may function as a unit during
      loading without separation. identification of secondary cracks from TEM
      fractographic analysis exemplifies the complex reaction to tensile stresses in
      multilayered joint systems that comprise materials of variable compliance.

PMID- 11317406
TI  - Bond strengths of self-etching primer adhesives to in vitro-demineralized dentin
      following mineralizing treatment.
AB  - PURPOSE: The purpose of this study was to determine if treatment of
      experimentally demineralized dentin with a calcium phosphate precipitating (CPP)
      solution could restore the bond strength of self-etching adhesives to that of
      normal mineralized control values. MATERIALS AND METHODS: The occlusal surfaces
      of human teeth were exposed for bonding. The teeth were assigned to a mineralized
      control group or one of three demineralized (40% phosphoric acid for 60 s)
      experimental groups. One of the experimental groups remained untreated, while the
      other two were treated with the CPP solutions for either 1 or 10 min. All
      experimental groups were then chemically dehydrated with ascending acetone
      concentrations to prevent shrinkage prior to bonding with Clearfil Liner Bond 2
      (LB2) or MacBond II (MBII). Composite buildups were made and vertically, serially
      sectioned into multiple slabs about 0.7 mm thick. Each slab was then trimmed for
      microtensile bond testing and SEM examination. RESULTS: Both self-etching
      adhesives produced high bond strengths to control mineralized dentin (ca 42 and
      37 MPa for LB2 and MBII, respectively). Acid etching with 40% phosphoric acid for
      60 s followed by chemical dehydration significantly lowered (p < 0.05) bond
      strength to 26 and 27 MPa for LB2 and MBII, respectively, and created hybrid
      layers between 7 and 8 microns thick. When the demineralized dentin was treated
      with the CPP solution for 1 min, the bond strengths increased (p < 0.05) to 39
      for LB2 and 42 MPa for MBII, and the hybrid layers were 11 microns thick.
      Increasing the CPP treatment time to 10 min lowered (p < 0.05) bond strengths but
      increased the hybrid layer thickness to 16 to 20 microns. CONCLUSION: The use of
      calcium phosphate precipitating solutions may permit higher bond strengths of
      self-etching primers to demineralized (e.g., caries-affected) dentin.

PMID- 11317408
TI  - Rewetting strategies for bonding to dry dentin with an acetone-based adhesive.
AB  - PURPOSE: The objective of this study was to investigate the effect of rewetting
      agents on bonding to etched and air-dried dentin. MATERIALS AND METHODS: For
      shear bond strength testing (SBS), the proximal surfaces of 90 molars were ground
      on wet SiC paper to prepare them for resin composite bonding with Gluma One Bond
      (Heraeus Kulzer, Germany). Dentin cavities were cut (O 3.5 mm, 1.5 mm deep) in 60
      molars and restored with Gluma One Bond/Charisma for evaluation of the marginal
      performance (MGW). The adhesive was applied on acid-etched and rinsed dentin
      after the following pretreatment techniques: A: moist; B: 15 s air dried; C
      through F: 15 s air dried, followed by 30 s rewetting with C: water; D: 35% HEMA;
      E: Gluma Primer; F: 5% glutardialdehyde; G through J: as C through F, but
      followed by 15 s air drying. SBS data were analyzed with ANOVA and Tukey's test,
      and MGW with Kruskal-Wallis and Mann-Whitney U-test (alpha = 0.05). RESULTS:
      Shear bond strengths of groups A and B were 20.3 and 1.1 MPa, respectively. The
      Tukey ranking of SBS results was [A=C=D=E] > [C=D=E] > [C=D=I] > H > [F=J] >
      [B=G]. Groups A, C, D, E, H, and I with 3 or 4 gap-free restorations each showed
      no differences in MGW (p > 0.05). In contrast, no gap-free specimens were found
      in groups B, F, G, or J, and marginal gaps were significantly larger (p < 0.05).
      CONCLUSION: Rewetting of dried dentin with water, 35% HEMA, or Gluma Primer
      resulted in effective bonding. Excessive drying after rewetting had no
      compromising effect on adhesion in the HEMA- and GLUMA-primed groups, whereas the
      water and glutardialdehyde-treated groups showed poor bonding.

PMID- 11317407
TI  - Buffering action of human dentin in vitro.
AB  - PURPOSE: The purpose of this study was to determine the relative contributions of
      the mineral and organic phases of dentin to its total buffering capacity and to
      compare the buffering abilities of normal and caries-affected dentin for acids
      used in adhesive dentistry. MATERIALS AND METHODS: Disks of normal and caries
      affected human coronal dentin 0.6 mm thick were prepared. Fifty microL of various
      acids were applied to the surface of mineralized or completely demineralized
      dentin for varying lengths of time. They were collected from the surface and
      combined with water rinses to permit titration of the total amount of acid
      applied, the amount recovered, the total amount that was taken up by the dentin,
      and the amount that diffused across dentin into 1 mL of water. Equal volumes of
      acids were applied to mineralized or demineralized dentin powder or
      hydroxyapatite powder. RESULTS: About 88% to 90% of applied acid was recovered
      from the surface; only 10% to 12% of the acid was taken up by dentin. Of the H+
      that was taken up, only 1% to 2% actually diffused across 0.6 mm of dentin.
      Increasing the application time of 37% phosphoric acid did not increase the
      amount of H+ that diffused across dentin. Increasing the concentration of
      phosphoric acid from 10% to 65% produced only slight increases in H+ diffusion
      across dentin. There was no difference in the buffering capacity of normal vs
      caries-affected dentin disks. Almost all of the buffering capacity of dentin is
      due to its mineral phase. CONCLUSION: The high buffering capacity of dentin and
      the high reactivity of H+ insure that little H+ diffuses through dentin more than
      0.6 mm thick.

PMID- 11317409
TI  - Nanoleakage of cervical restorations of four dentin bonding systems.
AB  - PURPOSE: The aim of this study was to evaluate the degree of nanoleakage of
      restorations placed in cervical preparations with dentin bonding systems.
      MATERIALS AND METHODS: The dentin bonding systems used were Single Bond, One Coat
      Bond, Prime & Bond NT/NRC, and PermaQuik. Ten saucer-shaped cervical preparations
      were bonded with one of the dentin bonding systems and restored with Silux Plus
      resin composite in each group. After 24 hours storage in 37 degrees C water,
      restorations were finished and the surrounding tooth surfaces were coated with
      nail varnish. The samples were immersed in 50% w/v solution of silver nitrate for
      24 hours, and exposed to photodeveloping solution for 8 hours. The samples were
      cut longitudinally through the center, polished, carbon coated and observed in a
      Field Emission SEM using backscattered electron mode. The degree of silver
      penetration along the preparation wall was observed and calculated as a
      percentage of the total preparation wall length. Results were analyzed by one-way
      ANOVA and LSD tests. RESULTS: PermaQuik demonstrated the lowest leakage score and
      the least silver deposition within the hybrid layer, while Prime & Bond NT/NRC
      showed the greatest leakage scores and the most silver deposition within the
      hybrid layer. Different nanoleakage patterns were observed for the different
      adhesive systems. CONCLUSION: First, the composition of each adhesive system may
      play a role in the different leakage patterns. Second, the current dentin bonding
      systems used in this study did not achieve perfect sealing at the restoration
      dentin interface. This may influence the durability of the bond to dentin.

PMID- 11317410
TI  - A simple method for single anterior tooth replacement.
AB  - PURPOSE: This article reports a case in which a recently extracted tooth was used
      as a natural tooth pontic bonded to the teeth on either side of the missing tooth
      using a Ribbond ribbon. MATERIALS AND METHODS: A bondable, reinforcing
      polyethylene ribbon was used to bond a natural tooth pontic to adjacent teeth.
      RESULTS: Acceptable esthetics were obtained and the result was satisfactory for
      the patient. CONCLUSION: After one year of clinical use, direct construction of a
      single-tooth replacement using the natural tooth pontic still provided
      satisfactory esthetics and function. The technology which makes this adhesive
      restoration possible is the development of a high strength, high molecular
      weight, biocompatible polyethylene fiber. This easily handled material must be
      evaluated in long-term clinical studies.

PMID- 11317411
TI  - Bonding of a self-etching primer to non-carious cervical sclerotic dentin:
      interfacial ultrastructure and microtensile bond strength evaluation.
AB  - PURPOSE: The objectives of this study were 1) to examine the ultrastructural
      features of the resin-sclerotic dentin interface following the application of
      Clearfil Liner Bond II sigma to natural cervical wedge-shaped lesions, and 2) to
      evaluate the regional tensile bond strength of this self-etching primer at
      different locations on natural and artificially-created cervical lesions.
      MATERIALS AND METHODS: Deep cervical natural lesions were bonded using the self
      etching primer. Micromorphology of the bonded interface at different locations
      within the lesions were examined using scanning electron microscopy (SEM),
      transmission electron microscopy (TEM) and scanning transmission electron
      microscopy/energy dispersive x-ray analysis (STEM/EDX). Ultrastructural features
      were further compared with the use of the same self-etching primer on artificial
      lesions created in sound cervical dentin. A nontrimming technique was used to
      evaluate the regional tensile bond strength from the occlusal, gingival, and the
      deepest central part of both natural and artificial cervical lesions. Beams with
      a mean area of 0.46 +/- 0.03 mm2 were prepared and were pulled to failure using a
      Bencor Multi-T testing device attached to an Instron universal tester. Bond
      strength results were evaluated using a two-way ANOVA design. RESULTS: A
      hypermineralized layer devoid of intact, banded collagen was invariably present
      on the surface of the natural lesions. Depending upon its thickness at different
      locations of the lesion, the action of a self-etching primer may be limited to
      this surface layer alone, producing a hybridized hypermineralized surface layer.
      Penetration of the self-etching primer into the underlying sclerotic dentin
      produced a hybridized complex containing a hybridized hypermineralized surface
      layer as well as a subsurface layer of hybridized intertubular dentin. Bacterial
      colonization of the lesion surface resulted in the formation of an additional
      zone of hybridized intermicrobial matrix over the surface of the lesions.
      Dentinal tubules remained blocked with sclerotic casts, and resin tags were
      rarely observed. Regional tensile bond strength results showed that the overall
      bond strength to natural sclerotic dentin was about 20% lower than sound cervical
      dentin, but was independent of the different locations within the lesions from
      which bond strength was evaluated. CONCLUSION: There were four factors that may
      have influenced the overall decrease in bond strength in natural cervical
      sclerotic lesions: a) the presence of a hybridized intermicrobial matrix together
      with entrapped bacteria may have weakened the bonds, b) inability of a self
      etching primer to etch through a thick, hypermineralized surface layer, c)
      presence of a layer of possibly remineralized, denatured collagen at the base of
      the hypermineralized surface layer, and d) retention of acid-resistant sclerotic
      casts that obliterate the tubular lumina and prevent effective resin tag
      formation.

PMID- 11317412
TI  - Bridging the gap in diabetes testing.

PMID- 11317413
TI  - Human herpesvirus 6: diagnosis of active infection.
AB  - HHV-6 is an opportunistic viral pathogen that has been demonstrated as the cause
      of often life-threatening illness in pediatric patients and transplant
      recipients. A substantial body of scientific evidence links HHV-6 to the etiology
      of such chronic diseases as multiple sclerosis. For these reasons, it is
      important that patients in these groups be screened for possible infection with
      HHV-6. Serological studies for IgG and/or IgM can be misleading, as are PCR
      analyses, which cannot distinguish between latent and actively replicating virus.
      Currently, the only reliable method for diagnosing an active infection with HHV-6
      is viral isolation.

PMID- 11317414
TI  - Direct determination of platinum in urine by electrothermal atomic absorption
      spectrometry.

PMID- 11317415
TI  - Evaluation of a coagulation analyzer.
AB  - The CA-6000 compared favorably to the well-established 1600C in terms of clinical
      utility. Its enhanced reagent capacity and open nature make it a wise instrument
      selection option.

PMID- 11317416
TI  - FTIR fiber optics and FT-Raman spectroscopic studies for the diagnosis of cancer.
AB  - The authors' preliminary investigation has shown that FTIR spectroscopy in
      conjunction with fiber optics can reflect differences between normal and
      malignant tissues. Further studies are being conducted to determine the
      applicability of the technique to cancer diagnosis.

PMID- 11317417
TI  - Automating preanalytics: total laboratory automation, preanalytical line, or task
      targeted?

PMID- 11317418
TI  - CLMA 2000: first-to-market product introductions.

PMID- 11317419
TI  - Review of Lab Automation 2000: clinical session review, Part 2--E-commerce,
      mobile cart, connectivity, and integrated futures.

PMID- 11317420
TI  - Mad Cow Crisis II: new casualties.

PMID- 11317421
TI  - Measuring exposure to pro- and anti-tobacco marketing among adolescents:
      intercorrelations among measures and associations with smoking status.
AB  - Exposure to tobacco-related marketing has been implicated as one of the risk
      factors for tobacco use among adolescents. However, tobacco-related marketing
      exposure has been measured in different ways in different studies, including
      perceived pervasiveness, receptivity, recognition, recall, and affect. It is not
      known whether these measures represent one or more underlying constructs and how
      these underlying constructs are associated with adolescent smoking status. This
      study analyzed data from 5,870 eighth-grade students in California, collected in
      1996-1997 as part of the Independent Evaluation of the California Tobacco
      Control, Prevention, and Education Program. An exploratory factor analysis of
      multiple measures of tobacco-related marketing exposure revealed four distinct
      factors: perceived pervasiveness of protobacco marketing, perceived pervasiveness
      of antitobacco marketing, recognition of specific anti-tobacco advertisements,
      and receptivity to protobacco marketing. Receptivity to pro-tobacco marketing
      showed the strongest association with smoking status; higher levels of
      receptivity were associated with higher levels of smoking. Two measures of
      exposure to anti-tobacco marketing (perceived pervasiveness of anti-tobacco
      marketing and recognition of specific anti-tobacco ads) were highest among
      established smokers and lowest among susceptible nonsmokers. The same pattern was
      evident for perceived pervasiveness of pro-tobacco marketing. Results suggest
      that exposure to tobacco-related marketing is a multidimensional construct, and
      each dimension may have a unique contribution to the process of smoking
      initiation. Because adolescents are exposed to numerous pro- and anti-tobacco
      messages, it is important to develop anti-tobacco media campaigns that can
      successfully counter pro-tobacco marketing efforts. Potential strategies include
      targeting the susceptible nonsmokers who are at high risk for smoking and
      developing messages to decrease receptivity.

PMID- 11317422
TI  - An intervention to increase fruit and vegetable consumption using audio
      communications: in-store public service announcements and audiotapes.
AB  - Consumers make an estimated 70% of their food purchase decisions as they shop.
      Effective presentation of information about healthier food selections at the
      point-of-purchase should have an impact on their decisions. This study was
      designed to evaluate the effectiveness of two audio formats on knowledge,
      attitudes, and beliefs about fruits and vegetables and on intake of these foods.
      Participants identified as "regular shoppers" (n = 374) in three intervention
      stores were recruited as they entered. They provided baseline demographic data,
      answered questions about their knowledge and beliefs about fruits and vegetables,
      and completed a checklist to assess fruit and vegetable intake. They were given
      two one-hour audiotapes and asked to play them within the next four weeks. In
      store public service announcements (PSAs) with information about fruits and
      vegetables were rotated every 30 minutes for four weeks. A control group (n =
      378), recruited in three other stores matched by demographic characteristics,
      provided the same information. They received an audiotape with stress reduction
      information. At posttest, the original series of questionnaires were
      readministered in telephone interviews with 87.7% of the original intervention
      group and 93.7% of the original control group. Knowledge scores in the
      intervention group increased significantly over baseline and as compared with the
      control group. Self-reported fruit and vegetable intake increased significantly
      in both groups, perhaps in part because of a seasonal effect. The increase from
      baseline was significantly higher in the intervention group and compared with
      controls. These findings support the further exploration of the use of audiotapes
      in nutrition education interventions.

PMID- 11317423
TI  - Impact evaluation of the "not me, not now" abstinence-oriented, adolescent
      pregnancy prevention communications program, Monroe County, New York.
AB  - "Not Me, Not Now" is an abstinence oriented, adolescent pregnancy prevention
      integrated communications program developed by Monroe County, NY. The evaluation
      utilized a cross-sectional time series approach in the analysis of items from
      several waves of youth surveys administered to two different age groups: (1) a
      survey of 7th and 8th graders on awareness, attitudes and intended behavior, and
      (2) the Youth Risk Behavior Survey administered to 9th through 12th graders. The
      trends found in the surveys demonstrated high levels of awareness of the program,
      changing attitudes and intended behaviors consistent with the program's messages.
      Analysis of pregnancy rates for 15-17 year-olds in the county were compared to
      reductions found in similar geographic areas. Pregnancy rates in Monroe County
      declined faster than in comparison areas. The authors conclude that there is a
      strong likelihood that the program had independent effect on the outcome of
      pregnancies in the population exposed to the program.

PMID- 11317424
TI  - Presenting risk information--a review of the effects of "framing" and other
      manipulations on patient outcomes.
AB  - Discussing risks and benefits of treatments or care options is becoming an
      increasingly important part of modern health care. This paper reviews the
      literature about manipulations of risk and benefit information in the clinical
      setting. There is a paucity of evidence in this field, particularly when
      examining specific manipulations. Only three categories of manipulation had three
      or more studies. The available evidence shows that the way information is
      presented can have significant effects on decisions made. The largest effects are
      evident when relative risk information is presented, as compared with absolute
      risk data. In addition, "loss framing" is more effective in influencing screening
      uptake behaviors than "gain framing" (odds ratio 1.18 [95% confidence interval
      1.01-1.38]). There is also a pattern of evidence from studies comparing simpler
      with more complex information, more data with less, and those comparing numerical
      with verbal descriptions of risks. These studies suggest that providing more
      information, and which is more understandable to the patient, is associated with
      improved patient knowledge and a greater wariness to take treatments or
      participate in trials. These findings can contribute to efforts to improve
      communication between professionals and patients.

PMID- 11317425
TI  - Risks, benefits, and conflicts of interest in human research: ethical evolution
      in the changing world of science.

PMID- 11317426
TI  - Defining and describing benefit appropriately in clinical trials.

PMID- 11317427
TI  - The ethical analysis of risk.

PMID- 11317429
TI  - Dealing with conflicts of interest in biomedical research: IRB oversight as the
      next best solution to the abolitionist approach.

PMID- 11317428
TI  - The ethics of clinical trials: a child's view.

PMID- 11317430
TI  - Pharmaceuticals: no duty to disclose price differentials to uninsured customers.

PMID- 11317431
TI  - Evidence: discovery and "medical peer review" committee privileges.

PMID- 11317432
TI  - ERISA: no preemption of state's HMO law requiring independent physician review.

PMID- 11317433
TI  - Employment: no discrimination for accommodation of patients' preference for
      female doctors.

PMID- 11317434
TI  - Disability and the ADA: learning impairment as a disability.

PMID- 11317435
TI  - Research guidelines: NIH issues guidelines for federally funded stem cell
      research.

PMID- 11317436
TI  - RICO: fraudulent concealment not barred by time.

PMID- 11317437
TI  - Internet and health care: DHHS releases final rule on electronic transactions
      standards.

PMID- 11317438
TI  - Insurance: patient protections for federal employees.

PMID- 11317439
TI  - [Over a decade minimal invasive surgery--retrospect and prospects. 10 years
      laparoscopic surgery--consolidation in a new market].

PMID- 11317440
TI  - [Laparoscopic surgery: expectations and reality].
AB  - Despite the rapid development and widespread application of laparoscopic
      operation techniques, only laparoscopic cholecystectomy and laparoscopic
      fundoplication have replaced the open operations as standard techniques. Nowadays
      only about 10% of appendectomies and 25% inguinal hernias are performed by the
      laparoscopic approach. Colorectal operations are rarely performed
      laparoscopically. Demanding operative skills and uncertainty about the
      oncological quality have hindered the spread of laparoscopic colorectal
      resections. Studies at specialized centers have shown that it is possible to
      follow the principles of oncological surgery. First results of small series
      promise similar long-term results, but large prospective randomized trials are
      still unpublished. Depending on the extent of the operative procedure,
      laparoscopic operations result in reduced postoperative pain, fewer adhesions,
      shortened postoperative atonia and improved convalescence in comparison with open
      surgery. The direct costs of laparoscopic procedures are higher than open
      operations as a result of longer operation times and expensive equipment. As a
      result of shorter hospitalisation and quicker return to work, the overall health
      care costs may be reduced, but strong unbiased evidence is still lacking.

PMID- 11317441
TI  - [Reduction of surgical access trauma: reliable advantages].
AB  - Minimizing the trauma of surgical access is becoming an essential task in modern
      surgery. The treatment has to become more comfortable for the patient and
      financial resources have to be considered. Minimally invasive surgery is one of
      the attempts to achieve this goal. A comparison of surgical procedures, such as
      cholecystectomy, fundoplication and sigmoid resection in diverticulitis, which
      are already routinely performed laparoscopically, should be suitable for
      evaluating whether minor access surgery is really advantageous. The value of
      minor access may be quantified by different parameters such as influence upon the
      immunologic function, lung function, postoperative pain, time of hospitalization,
      return to work and duration of convalescence, as well as a comparison of the
      effects upon the quality of life index. The data concerning the effects upon
      immunology are not unequivocal. All in all, the degree of postoperative
      inflammation seems to be lower after laparoscopic surgery. There is no doubt that
      there is far less impairment on lung function, the results are better as far as
      postoperative pain is concerned, and hospitalization and duration of
      convalescence are shorter. It is also evident that immediately after the
      operation the quality of life index is superior, which, however, levels out in
      the course of time. The advantage of minimally invasive surgery is really
      apparent only after the mastering of the so-called "learning curve" and in cases
      of benign malignancies. The role of the minor access approach in oncological
      surgery is, however, not yet defined.

PMID- 11317442
TI  - [Minimal invasive surgery. Aspects of surgical oncology of the gastrointestinal
      tract].
AB  - The general potential and current position of minimally invasive surgery for the
      surgical treatment of malignant tumours of the gastrointestinal tract are
      discussed. A reliable validation of these procedures for tumour surgery is still
      impossible due to the lack of long-term results, the selective experience, and
      the ongoing process of learning and development. However, it seems clear that
      minimally invasive procedures will have an important position within surgical
      oncology. This is especially true with respect to improved staging of
      gastrointestinal tumours by laparoscopy and various palliative procedures that
      may be performed laparoscopically. Minimally invasive procedures may suffice for
      the treatment of certain, highly selected cases of preneoplastic and early
      cancerous lesions. The definitive acceptance of minimally invasive procedures in
      the future will require further clinical, preferably randomised trials, comparing
      the advantages of the minimally invasive access route to possible long-term
      disadvantages with regard to recurrence-free and overall survival.

PMID- 11317443
TI  - [New technologies in laparoscopic surgery].
AB  - The technology associated with endoscopic surgery continues to evolve as a result
      of industrial R & D and research within academic surgical departments with
      interest in surgical endoscopic and remote handling technology. Some of the
      developments in the last ten years are reviewed. The problem concerning health
      technology assessment (HTA) in relation to new devices/instrumentation and
      procedures is discussed. Randomised controlled clinical trials are unsuited for
      the initial HTA of technology-dependent interventions, and for this reason, an
      alternative system, controlled stepwise evaluation (CSE) is proposed.

PMID- 11317444
TI  - [Effect of the learning phase on safety and efficiency of laparoscopic
      fundoplication].
AB  - The introduction of laparoscopic techniques into surgical practice has required a
      learning process on the part of the surgeons involved. The duration, morbidity,
      and functional outcome of laparoscopic fundoplication were evaluated in our
      institution's first 146 cases. During a 34-month period the patients underwent
      laparoscopic Nissen (n = 102) or Toupet (n = 44) fundoplication. Conversion to
      open access was necessary in 7 cases, re-operation for complications in 2, all
      among the first 40 cases of the series. The median operating time was 165 min
      (range 75-375) in the first 40 cases, and 105 min (range 50-235) thereafter (P <
      0.001). Body mass index, grade of esophagitis, and the surgeon's experience were
      independent predictors of the operating time. One hundred and thirty-four
      patients (92%) could be evaluated for recurrence of reflux, which was encountered
      in 2 (5%) of the first 40 cases and 8 (8%) of 94 patients in the later group.

PMID- 11317445
TI  - [Endosonography in epithelial rectal tumors. Value of a differentiated therapy
      concept].
AB  - INTRODUCTION: Endorectal ultrasound (EU) is the most important examination for
      pretherapeutic stratification of primary rectal tumors. Preoperative histology
      and endosonography determine the therapeutic strategy by using the criteria of
      depth of infiltration (uT) and lymph node status (uN). METHODS: The effectiveness
      of endoluminal ultrasound in the preoperative differentiation between locally
      restricted tumors (adenomas and "low-risk" carcinomas, uT0/1, G1-2) and advanced
      rectal carcinomas (uT3) was assessed in a retrospective study of 284 patients. In
      the examination period (UZ) from 3/94 to 12/97 (UZ I) 104 patients (group 1) were
      examined with a 7-MHz endoprobe, and from 1/98 to 12/99 (UZ II), 116 (group 2)
      with a 10-MHz endoprobe. Additionally, in 64 patients (group 3) with an advanced
      uT3/4 or uN + tumor we compared the accuracy of ultrasound with computed
      tomography (CT). In this group 32 patients were restaged by EU and CT after
      preoperative chemoradiation. The results of praoperative endorectal ultrasound
      were correlated with the postoperative histological data. RESULTS: Concerning the
      whole period (UZ I and II) we achieved a total hit rate of 83.6% for adenomas and
      "low-risk" carcinomas (uT0/1, G1/2) by EU (79.8% in UZ I, 87.1% in UZ II). For
      advanced rectal carcinoma (> or = uT3) we found a total accuracy of 87.3% (82.7%
      in UZ I, 91.4% in UZ II). In 62 cases endosonographic lymph node status was
      correlated with postoperative histology during UZ II, with a hit rate of 64.5%.
      In group 3 (n = 64), in 32 patients without preoperative chemoradiation we found
      an accuracy for depth infiltration of 93% (EU) and 82% (CT). Concerning lymph
      node status there was a correlation of 57% (EU) and 64% (CT). After preoperative
      chemoradiation (n = 32) we found an accuracy of 91% (EU) and 73% (CT) for depth
      infiltration--for lymph node status 70% (EU) and 82% (CT). CONCLUSIONS: High
      accuracy in endoluminal ultrasound leads to a secure and differentiated
      stratification of therapy in primary rectal tumors. The hit rate concerning depth
      of infiltration is higher for EU than for CT both before and after
      chemoradiation, but not regarding lymph node status.

PMID- 11317446
TI  - [A new video documentation system for rigid procto-rectoscopy].
AB  - INTRODUCTION: Disadvantages of rigid procto-rectoscope systems are the lack of
      sufficient visual documentation, data processing and the insufficient
      demonstration for educational purposes. Therefore a video documentation system
      for rigid procto-rectoscopy (Endovision Telecam SL) was developed. METHOD: For
      evaluation of the Endovision Telecam SL, the system was compared to the
      conventional technique over a 6-month period. RESULTS: The Endovision Telecam SL
      offers the advantage of flexible video-endoscopy and displays an excellent
      quality of documentation for rigid procto-rectoscopy. The handling of the system
      is slightly more time-consuming and difficult and the use is limited to cases
      without severe bleeding and stool contamination. CONCLUSIONS: The Endovision
      Telecam SL combines the advantages of flexible video-endoscopy in documentation,
      demonstration and data processing with the practibility of rigid instruments for
      procto-rectoscopy. In the present set-up the system is still limited to special
      indications and should be combined with conventional procedures.

PMID- 11317447
TI  - [Hepatobiliary cystadenoma].
AB  - INTRODUCTION: Hepato-biliary cystadenomas are rare intrahepatic cystic tumours.
      The correct preoperative diagnosis of this lesion is difficult. METHODS: We
      report four cases of hepato-biliary cystadenoma treated in our department from
      January 1995 to December 1999. RESULTS: The symptoms were unspecific.
      Preoperative computed tomography showed signs of an echinococcal cystic lesion in
      two patients, but there were no antibodies against an echinoccocal species in the
      serum. We performed a complete resection of the cystic tumour in three patients
      and a subtotal resection of a hepato-biliary cystadenoma in one, because of
      involvement of the hepatic portal structures. We did not find a malignant
      transformation to a hepato-biliary cystadenocarcinoma. CONCLUSION: Complete
      excision of a cystadenoma with a wide margin of normal liver tissue is the
      treatment of choice, because several reports have described malignant
      transformation of this kind of tumour. Taking a rapidly frozen section during the
      operation is an important step in the treatment of cystic liver lesions. A cystic
      liver lesion with several walls and a elevated CA 19-9 can predict a mucinous
      cystadenoma or cystadenocarcinoma.

PMID- 11317448
TI  - [Single injuries to distal leg arteries].
AB  - The appropriate treatment of an injury to a single arterial vessel of the calf is
      still a matter of discussion. Isolated injury of one of the calf arteries is
      generally not considered to cause severe ischemia of the leg. Other factors such
      as the degree of concomitant trauma to bones, nerves, veins and soft tissue,
      which may impair collateral circulation, seem to represent the real threat for
      the survival of the extremity. On the other hand, high numbers of amputations
      were reported after the Second World War following ligation of an injured single
      vessel of the calf. Concomitant injuries are poorly documented in these reports.
      Consequently a good physical examination as well as arteriography, duplex
      ultrasound scan and a high index of suspicion are mandatory to evaluate the
      impaired circulation of the calf and to prevent hasty ligation of a single
      vessel.

PMID- 11317449
TI  - [Robot-assisted laparoscopic cholecystectomy and fundoplication--initial
      experiences with the Da Vinci system].
AB  - We report on our first five robot-assisted laparoscopic cholecystectomies and one
      fundoplication (Da Vinci system). No postoperative complications were observed.
      For the cholecystectomies (three elective and two acute cases) mean operation
      time was 1 h 35 min, and mean hospital stay was 5 days; for fundoplication the
      operation time was 2 h 15 min. The main advantages seem to be improved
      visualization by using a stereo camera und ease of precise dissection by
      micromechanical instruments directed by masterslaves from a distant console. The
      main disadvantage is the high cost. To fully evaluate the benefit for the
      patient, prospective clinical trials are warranted.

PMID- 11317450
TI  - [Spiral trocar--a new trocar concept].
AB  - INTRODUCTION: We would like to introduce a new trocar technique for minimal
      invasive surgery. The new trocar is a spiral whose coil becomes ever increasingly
      stronger towards the centre. Because of this, there is a smooth transition
      between spiral, screw and rod. The outer diameter remains the same. The spiral
      trocar is screwed through the abdominal wall like a corkscrew. Because of this,
      the primary channel of puncture runs spirally. Furthermore, the channel is
      dilated and centralised so that the trocar's rod together with its sleeve can be
      pushed through the abdominal wall. This trocar design demonstrates the following
      advantages: The trocar can be screwed through the abdominal wall in a controlled
      manner without having to apply axial pressure. This prevents any unintentional
      perforation of organs. Because different layers of the tissue are penetrated at
      different places, they overlap, thus sealing one another after removal of the
      sleeve. The puncture channel was minimal, thus leaving very little risk of trocar
      site hernia. METHODS: The spiral-trocar was examined and compared with other
      types of trocars in vivo and vitro. RESULTS: During these tests, the spiral
      trocar demonstrated a high level of safety and good usability. DISCUSSION: The
      spiral-trocar is an easily cleanable, reusable product without a mechanical
      sealing device and can be used together with most sleeves. This makes it very
      cost effective.

PMID- 11317451
TI  - [Vascular complications in thoracic outlet syndrome: combined transaxillary
      revascularization and rib resection].
AB  - Based on two patients with vascular complications in thoracic outlet-syndrome,
      the anatomic and pathophysiologic principles prior to surgery are discussed.
      Causative therapy including rib resection and elimination of the embolic source
      in the subclavian artery is often supplemented by peripheral revascularization
      with bypass, lysis and/or sympathectomy. The transaxillary approach seems to be
      optimal, combining minimally invasive principles with a long exposure of the
      subclavian artery from segment 3 to the proximal axillary artery.

PMID- 11317452
TI  - [Invagination caused by angiolipoma of the small intestine--a rare cause of
      occult gastrointestinal hemorrhage].
AB  - We present the case of a 71-year-old woman who was hospitalized because of a
      severe hip contusion. She had no symptoms or clinical signs of abdominal disease.
      Routine blood testing showed anemia, presumably owing to occult bleeding.
      Ultrasonographic abdominal screening revealed ileo-ileal intussusception with a
      central hyperechoic tumor suggestive of a lipoma as lead point. This diagnosis
      was confirmed at surgery, where a small bowel resection was performed. Histologic
      examination disclosed a benign angiolipoma of the ileum with a superficial
      shallow ulceration which obviously was the source of the occult blood loss.
      Diagnostic and therapeutic procedures and a literature review are discussed.

PMID- 11317453
TI  - [Benign, pulmonary metastatic leiomyoma of the uterus].
AB  - Pulmonary nodules resected in 10 patients were histologically classified as
      benign metastatic leiomyoma of the uterus. Hysterectomy because of myoma had been
      performed between 0 and 24 years earlier (median 14.9 years). Between 1 and 27
      nodules were found in one or both lungs. Patients presenting with a single nodule
      had it resected with diagnostic intent and were followed up. Multiple nodules
      were resected if the loss of parenchyma was tolerable; otherwise, one lesion was
      resected for diagnosis. In some cases antihormonal therapy was performed
      postoperatively. The median duration of follow-up was 4.7 years. In this time, no
      local complication occurred, and no patient died of this disease. Apparently,
      benign metastatic leiomyoma of the uterus biologically shows benign behaviour.
      New manifestation or progressing growth of non-resected lesions does occur,
      however. Consequently, regular follow-up is required. Local complications
      indicate surgical intervention.

PMID- 11317454
TI  - [Development of a standardized instrument for quantitative and reproducible
      rehabilitation data assessment after polytrauma (HASPOC)].
AB  - INTRODUCTION: Previous scoring systems for measurement of the quality of outcome
      are based on scores regarding injuries to individual body regions. Known scores
      which describe several organ regions are of no importance for trauma patients.
      Therefore a new rehabilitation outcome evaluation score was developed at our
      hospital. METHODS: Based on a prospective reinvestigation, a score system was
      developed that allows a quantitative appraisal of the subjective and objective
      outcome. A complete physical examination was performed, including ROM, neurologic
      examination and strength analysis. Part I (113 questions) is to be filled out by
      the patient; part II (191 questions) focusses on different body regions, physical
      examination and functional scoring. Included are the MFA, FIM, GCO and Frankel
      score. A final score (HASPOC) was developed to give a quantitative result of the
      outcome. RESULTS: The new score has a range from 5 to 411 points. One hundred and
      fifty patients were re-examined. The mean follow-up time was 2.2 +/- 0.1 years.
      The SF 12 indicated an outcome more than satisfactory in 63% of cases. The MFA
      demonstrated moderate or severe restrictions in 41%, in the case of injuries of
      the lower extremity in 52% of patients. The HASPOC indicated a mean of 44.5
      points. CONCLUSION: This paper describes the development, structure, and the
      quantitative outcome of rehabilitation in polytrauma patients. This standardized
      rehabilitation instrument deals with a very heterogeneous patient population and
      shows the rehabilitation deficits accurately. Implemented recognized evaluations
      allow comparison of these results with those of other scoring systems.

PMID- 11317455
TI  - [Necrotizing soft tissue infections].

PMID- 11317456
TI  - [Proposal to the Federal Medical Office for presentation at the 104th German
      Medical Congress 2001 in Ludwigshafen: surgery].

PMID- 11317457
TI  - [Efficiency through quality. Determining the basic responsibilities of
      physicians].

PMID- 11317458
TI  - [DRG's--organizational framework].

PMID- 11317459
TI  - [Australian DRG--the most important case groups for surgery].

PMID- 11317460
TI  - [DRG practice].

PMID- 11317461
TI  - [Publication of GOA Committee reimbursement recommendations on the internet sites
      of the BDC].

PMID- 11317462
TI  - Expanded role for ARBs in cardiovascular and renal disease? Recent observations
      have far-reaching implications.
AB  - The ARBs are a new class of drugs with broad therapeutic potential in
      cardiovascular disease. These agents act by selectively inhibiting the AT1
      subtype of the angiotensin II receptors. They are effective antihypertensive
      agents with promise, theoretically, in the prevention and regression of
      ventricular hypertrophy. They are safe and well tolerated in patients with CHF
      and might be effective in improving survival and reducing morbidity. ARBs also
      might have a similar role in improving the clinical outcomes of patients with
      coronary artery disease and chronic nephropathy. Their precise role in the
      treatment and prevention of cardiovascular and renal disease should be
      established by several ongoing clinical trials.

PMID- 11317463
TI  - Is it food allergy? Differentiating the causes of adverse reactions to food.
AB  - Foods can produce adverse symptoms in various ways, and the patient's history can
      help determine whether allergy or some other mechanism is responsible. The
      history has limitations, however, as it is primarily subjective. Therefore,
      diagnostic confirmation is very important. Strict avoidance of the allergenic
      food is the primary course of treatment. Education is imperative to ensure that
      patients understand food labels and recognize the different names used to
      designate a specific food. Prompt treatment with epinephrine when an acute
      reaction occurs can make a life-or-death difference.

PMID- 11317464
TI  - Letters from the front. Responses provide true-life stories of medical school
      debt and its effects.

PMID- 11317465
TI  - How can chronic heel pain be treated?

PMID- 11317466
TI  - Patient notes: chronic heart failure.

PMID- 11317467
TI  - Reducing cardiovascular risk in diabetes. Which factors to modify first?
AB  - Up to 80% of diabetic patients die of macrovascular complications, including CAD,
      stroke, and peripheral vascular disease. Because of the growing numbers of
      diabetic patients and the increased mortality after their first cardiovascular
      event, it is critical to identify and treat risk factors early and aggressively
      in these patients. Numerous studies in patients with type 2 diabetes have shown
      the benefits of aggressive treatment of blood pressure and lipids to levels that
      10 years ago would have seemed abnormally low. The downward changes in "normal"
      limits can be frustrating to primary care physicians, but advances in treatment
      are redefining "normal" levels required to avoid complications in this high-risk
      population.

PMID- 11317468
TI  - What's ahead in glucose monitoring? New techniques hold promise for improved ease
      and accuracy.
AB  - Advances in blood glucose monitoring have made it easier, more comfortable, and
      more practical for patients to monitor frequently. The new meters for
      intermittent monitoring are smaller and less dependent on technical aptitude than
      older models. They require less blood, and many provide downloadable information
      for glucose analysis. Data systems used with new meters provide valuable
      information that can dramatically improve glycemic control. Continuous glucose
      sensing (figure 4) is another major breakthrough in management of diabetes.
      Current systems allow only retrospective analyses, but real-time readings should
      be available in the near future. Such technological advances hold promise for
      preventing both hypoglycemia and hyperglycemia and for reducing the risk of long
      term complications associated with diabetes. An artificial, mechanical islet cell
      may be the big next step toward bringing this disease under control. By combining
      continuous glucose monitoring data with continuous insulin delivery via an
      external or an implantable insulin pump, the outlook promises to be much brighter
      for patients with type 1 diabetes.

PMID- 11317469
TI  - Lipotoxicity and glucotoxicity in type 2 diabetes. Effects on development and
      progression.
AB  - Excess fat, excess glucose, or both act on diverse cells and tissues to
      counteract insulin-mediated glucose uptake, hepatic regulation of glucose output,
      and insulin secretion. These effects are labeled lipotoxicity and glucotoxicity
      because, when severe enough, each may contribute to the diabetic state. Lifestyle
      modifications and certain new pharmacologic agents may be effective in modulating
      these effects and could prove useful in primary prevention of type 2 diabetes.

PMID- 11317470
TI  - Eating disorders in adolescents with type 1 diabetes. A closer look at a
      complicated condition.
AB  - The cultural drive to be thin can lead to eating disorders in many women and
      girls. In adolescent females with diabetes, the increased focus on eating and the
      weight gain associated with good glycemic control likely increase their
      susceptibility to abnormal eating. It is clear that nonspecified and subthreshold
      eating disorders, and possibly bulimia and anorexia, are more common in this
      group of patients. Good nutritional counseling to help patients avoid weight gain
      and family counseling to improve communication between patients and their
      families may help decrease this risk. Intentional insulin omission is a frequent
      means of preventing weight gain or increasing weight loss in adolescent females
      with type 1 diabetes. Eating disorders should be suspected in patients with
      recurrent diabetic ketoacidosis or poor glycemic control that is resistant to
      attempts at improvement. Treatment includes decreasing dietary restraint,
      promoting healthy eating, and either psychiatric counseling or psychologic
      intervention, or both.

PMID- 11317471
TI  - Curious bloody sputum causes concern. Wegener's granulomatosis.

PMID- 11317472
TI  - A placebo-controlled, double-blind, randomised trial of magnesium-pyridoxal-5'
      phosphate-glutamate for hypercholesterolaemia and other clinical-chemical risk
      factors of cardiovascular disease in a primary care setting.
AB  - BACKGROUND: Lipid-lowering drugs are extensively used in primary care to reduce
      the risk of cardiovascular disease (CVD). Apart from high total cholesterol (TC),
      several other clinical-chemical variables are associated with the risk of CVD.
      Magnesium-pyridoxal-5'-phosphate-glutamate (MPPG) has been found to have a
      positive influence on TC levels and other clinical-chemical values in some
      selected populations. OBJECTIVE: To assess, in a general practice (GP) setting,
      the efficacy and clinical effectiveness of MPPG in the treatment of clinical
      chemical risk factors for CVD. DESIGN: Randomised double-blind, placebo
      controlled, clinical trial, lasting 12 months. PATIENTS: Adults (25-66 years) in
      an average Dutch village population with serum cholesterol levels between 7.0
      mmol/l and 9.9 mmol/l. INTERVENTION: Subjects were assigned at random to
      treatment with MPPG (3 x 150 mg daily) or placebo. Clinical-chemical parameters
      were assessed at 1, 3, 6, 9 and 12 months (t1, t2, t3, t4, t5). Efficacy was
      measured at t2. Long-term effect (clinical effectiveness) was measured by
      combining the results at t2, t3, t4 and t5 (t2-5). OUTCOME MEASURES: TC
      (primary), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein
      cholesterol (HDL-C), triglycerides, apolipoprotein-A1 (Apo-A1), apolipoprotein
      B100 (Apo-B), fibrinogen and lipoprotein a [Lp(a), secondary]. RESULTS: No
      statistically significant differences in the efficacy and effectiveness of TC
      were found between the MPPG group and the placebo group. The same was
      demonstrated for the other clinical-chemical values, except for LDL-C
      (effectiveness, P = 0.04). CONCLUSIONS: Efficacy and effectiveness of MPPG are
      too poor to be of relevance for application as a lipid-lowering drug in GP.

PMID- 11317473
TI  - An investigation into the effects of cetirizine on cognitive function and
      psychomotor performance in healthy volunteers.
AB  - OBJECTIVE: The cognitive and psychomotor effects of 2.5, 5 and 10 mg cetirizine,
      a second-generation H1 receptor antagonist, were compared with loratadine 10, 20
      and 40 mg, promethazine 25 mg and placebo in 24 healthy volunteers in a double
      blind, randomised cross-over study. METHODS: Following each dose, subjects were
      required to perform a series of tests of cognitive function and psychomotor
      performance at 1.5, 3 and 6 h post-dose. The test battery consisted of critical
      flicker fusion (CFF), choice reaction time (CRT), compensatory tracking task
      (CTT) and assessment of subjective sedation (LARS). RESULTS: Cetirizine and
      loratadine at all doses tested were not significantly different from placebo in
      any of the tests used. However, as expected for a verum, all measures with the
      exception of CTT were significantly disrupted by promethazine (P < 0.05).
      Promethazine caused a reduction in CFF threshold at all test points; these
      differences were significant at 3 h and 6 h post-dose (P < 0.05). There was also
      a significant increase in total reaction time at 3 h post-promethazine
      administration. Subjective reports of sedation were significantly greater
      following the administration of promethazine at all time points (P < 0.05).
      CONCLUSIONS: These results allow the conclusion that cetirizine at its
      recommended therapeutic dose of 10 mg is demonstrably free from disruptive
      effects on aspects of psychomotor and cognitive function in a study where the
      psychometric assessments have been shown to be sensitive to impairment, as
      evidenced by the effects of the positive control, promethazine 25 mg.

PMID- 11317474
TI  - Effects of fluvastatin on biliary lipids in subjects with an elevated cholesterol
      saturation index.
AB  - OBJECTIVE: 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors
      have been suggested as agents to reduce the biliary cholesterol saturation index
      (CSI) in duodenal bile and therefore might be supportive in primary or secondary
      prevention of gallstones. However, the efficiency of the therapy seems to depend
      on both the HMG-CoA reductase inhibitor used and the study population selected.
      METHODS: We therefore investigated the effect of a high-dose application of
      fluvastatin on biliary lipid composition in 21 subjects exhibiting mild
      hypercholesterolaemia and a history of current gallstones or cholecystectomy due
      to gallstone disease. Subjects were treated either with 40 mg fluvastatin twice
      per day over a 3-month period (n = 14) or with placebo (n = 7). Bile samples were
      aspirated during endoscopy after intravenous ceruletid stimulation before and
      after therapy. RESULTS: Both groups were comparable in CSI (mean +/- SD) at
      baseline (1.78 +/- 0.2 placebo vs. 1.97 +/- 0.4 verum). CSI significantly
      decreased in the verum group to 1.45 +/- 0.4 (P = 0.003) mainly due to increased
      phospholipid levels, whereas no difference was observed in the placebo group
      (1.85 +/- 0.7, n.s.). In addition, the verum group exhibited a significant
      reduction of hydrophobic deoxycholic acid, which has been reported to induce
      cholesterol crystal precipitation, and an increase of hydrophilic cholic acid.
      CONCLUSION: Fluvastatin might decrease the risk of cholesterol gallstone
      formation in patients with elevated biliary CSI during long-term treatment by
      reduction of biliary cholesterol saturation and percentage change in deoxycholic
      acid content.

PMID- 11317475
TI  - Cytochrome P450 isoforms involved in melatonin metabolism in human liver
      microsomes.
AB  - OBJECTIVE: The present study was carried out to identify the cytochrome P450
      enzyme(s) involved in the 6-hydroxylation and O-demethylation of melatonin.
      METHODS: The formation kinetics of 6-hydroxymelatonin and N-acetylserotonin were
      determined using human liver microsomes and cDNA yeast-expressed human enzymes
      (CYP1A2, 2C9 and 2C19) over the substrate concentration range 1-1000 microM.
      Selective inhibitors and substrates of various cytochrome P450 enzymes were also
      employed. RESULTS: Fluvoxamine was a potent inhibitor of 6-hydroxymelatonin
      formation, giving 50 +/- 5% and 69 +/- 9% inhibition at concentrations of 1
      microM and 10 microM, respectively, after incubation with 50 microM melatonin.
      Furafylline, sulphaphenazole and omeprazole used at low and high concentrations
      substantially inhibited both metabolic pathways. cDNA yeast-expressed CYP1A2,
      CYP2C9 and CYP2C19 catalysed the formation of the two metabolites, confirming the
      data obtained with specific inhibitors and substrates. CONCLUSIONS: Our results
      strongly suggest that 6-hydroxylation, the main metabolic pathway of melatonin,
      is mediated mainly, but not exclusively, by CYP1A2, the high-affinity enzyme
      involved in melatonin metabolism, confirming the observation that a single oral
      dose of fluvoxamine increases nocturnal serum melatonin levels in healthy
      subjects. Furthermore, the results indicate that there is a potential for
      interaction with drugs metabolised by CYP1A2 both at physiological levels and
      after oral administration of melatonin, while CYP2C19 and CYP2C9 are assumed to
      be less important.

PMID- 11317476
TI  - Multiple-dose pharmacokinetics confirm no accumulation and dose proportionality
      of the novel promotile drug tegaserod (HTF 919).
AB  - OBJECTIVE: To evaluate the steady-state pharmacokinetics (PK) and dose
      proportionality of the selective 5-HT4 receptor partial agonist tegaserod (HTF
      919) in healthy subjects. METHODS: Eighteen subjects were given 2, 6, or 12-mg
      doses of tegaserod twice daily (b.i.d.) for 5 days, with PK and safety
      assessments made during the 12 h or 24 h following first administration, and 12 h
      after the final dose. RESULTS: Tegaserod was rapidly absorbed [time to reach
      measured maximum plasma concentration after multiple administrations (tmax,ss) 1
      h]. Steady-state PK were consistent with single-dose PK characteristics
      supporting that there was no accumulation of tegaserod in plasma based on
      systemic exposure. Mean measured maximum plasma concentration after multiple
      administrations (Cmax,ss) and area under the plasma concentration-time curve over
      one dosing interval (tau, 0-12 h after drug administration, AUC tau) were between
      0.7 +/- 0.3 ng/ml and 5.6 +/- 2.9 ng/ml and 2.4 +/- 1.3 h.ng/ml and 20.4 +/- 14.0
      h.ng/ml, respectively, indicating dose-proportional PK of tegaserod in the range
      2-12 mg b.i.d. Tegaserod was safe and well tolerated. No serious adverse events
      were reported. CONCLUSION: Tegaserod exhibits no accumulation and dose
      proportional PK after multiple doses.

PMID- 11317477
TI  - Inhibitory effect of troglitazone on glucuronidation catalyzed by human uridine
      diphosphate-glucuronosyltransferase 1A6.
AB  - OBJECTIVE: Troglitazone is a useful new thiazolidinedione oral antidiabetic
      agent, but it is unpredictably hepatotoxic in about 1.9% of patients. In vitro
      studies of drug interactions are important in understanding the basis for the
      pharmacological and toxicological actions of drugs. In the present study, we
      investigated whether troglitazone inhibits uridine diphosphate (UDP)
      glucuronosyltransferase 1A6 (UGT1A6) activity. METHODS: Human cDNA-expressed
      UGT1A6 was coincubated with troglitazone (inhibitor) and 1-naphthol (substrate).
      The glucuronidation of 1-naphthol was determined to establish a 50% inhibitory
      concentration (IC50) and an inhibition (Ki) value. RESULTS: Troglitazone
      inhibited UGT1A6 activity with an IC50 of 28 microM at a 1-naphthol concentration
      of 20 microM. The inhibition was a mixed-type mechanism with a Ki value of 20
      microM. CONCLUSION: Inhibitory effect of troglitazone is weak, however, co
      administration of troglitazone might carry a drug concentration into the toxic
      range when the concentration approaches a threshold of toxicity by an inherent
      reduction of UGT1A6 activity.

PMID- 11317478
TI  - Influence of gender on the pharmacokinetics, safety, and tolerability of
      cerivastatin in healthy adults.
AB  - The pharmacokinetics, safety, and tolerability of cerivastatin, a synthetic HMG
      CoA reductase inhibitor were studied in 49 healthy volunteers. In this double
      blind, parallel group, multiple-dose study, volunteers were randomized as age
      matched, male-female pairs and stratified into younger (18-65 years,
      premenopausal females) or older (65-85 years, postmenopausal females) groups.
      Thirty-two (16 female, 16 male) subjects received 0.2 mg cerivastatin daily for 7
      days; 17 received placebo. Between all males and females, no differences in
      cerivastatin pharmacokinetics were observed. The AUCnorm in older females was 21%
      higher than in older males, while the AUCnorm in younger females was 26% lower
      than in younger males. The Cmax in older females was 30% higher than in age
      matched males or younger males and females. All other pharmacokinetic parameters,
      including half-life, tmax, accumulation ratios, and steady state plasma levels
      were similar in all treatment groups. The most common adverse events, including
      headache (4), dyspepsia (4), and rash (4), were equally distributed between
      groups. Treatment-emergent elevations (< 2 x ULN) in creatine kinase occurred in
      one subject. Transaminase elevations occurred in nine subjects, most were less
      than 3 x ULN, and were equally distributed between groups. In conclusion,
      cerivastatin was well tolerated. The minor differences in the pharmacokinetics of
      cerivastatin 0.2 mg between genders does not require modification of dosage.

PMID- 11317479
TI  - Pharmacokinetics of emedastine difumarate, a new anti-histaminic agent in
      patients with renal impairment.
AB  - OBJECTIVE: Emedastine difumarate is a new H1 receptor antagonist with well
      defined pharmacokinetic and pharmacodynamic profiles in healthy volunteers.
      However, to date it is not known whether impaired renal function in patients with
      chronic renal insufficiency affects its pharmacokinetics and probably also its
      tolerability. Therefore, we here set out to compare the pharmacokinetics of
      emedastine difumarate in patients suffering from different degrees of renal
      failure with a control group of healthy volunteers. METHODS AND RESULTS: For this
      purpose we conducted an open, single-centre, comparative parallel group study in
      patients and healthy volunteers. Emedastine difumarate 2 mg was administered
      orally to the study population in single and seven repetitive doses twice daily
      (b.i.d.). Pharmacokinetics differed markedly between volunteers (n = 6) and
      patients (n = 17). The maximum serum concentration of emedastine (Cmax), area
      under the serum concentration-time curve, mean residence time and terminal
      disposition half-life were significantly higher in patients (P < 0.05), while
      time to reach Cmax and apparent volume of disposition were not statistically
      different after single and repeated (steady-state) oral administrations. Blood
      pressure and heart rate were also not affected by the study medication.
      CONCLUSION: The present study shows that impaired renal function alters the
      pharmacokinetics of emedastine in plasma. Thus, dose adjustment of emedastine
      difumarate is advisable in patients with impaired renal function.

PMID- 11317480
TI  - Initial uptake in use of sildenafil in general practice.
AB  - OBJECTIVE: To assess the initial uptake in use and co-prescribing patterns of
      sildenafil. METHODS: We examined prescription details of the Eastern Health Board
      Region (including Dublin) of the General Medical Services (GMS) in Ireland, which
      provides detail on prescriptions dispensed in primary care for this population (n
      = 334,031). We identified 1422 patients who received 3740 prescriptions for
      sildenafil over a 6-month period (July 1999-December 1999) and determined the
      percentage of patients who were co-prescribed nitrate therapy, medications which
      may interact with sildenafil and medications associated with impotence. RESULTS:
      We identified 1422 (1.4% of the male population over 16 years who might be
      expected to suffer from erectile dysfunction given an overall prevalence of 10%)
      who received a prescription for sildenafil over the study period at a cost of
      0.14% of the annual drug budget. Up to 2.5%, 6% and 25% of patients were co
      prescribed, respectively, nitrate therapy, potentially interacting drugs and
      drugs associated with impotence. CONCLUSION: The initial uptake and cost
      associated with sildenafil was lower than expected. The rate of prescribing of
      nitrates and other potentially interacting medications was found to be low.
      Medication use may also contribute to erectile dysfunction in this population of
      patients.

PMID- 11317481
TI  - Pharmacosurveillance and quality of care of thalassaemic patients. A large scale
      epidemiological survey.
AB  - OBJECTIVE: For adolescent thalassaemic patients, parenteral iron-chelation
      therapy is still a burden and a major reason for unsatisfactory compliance. The
      introduction of a new pharmaceutical preparation of deferoxamine (Desferal)
      claimed to be better tolerated was accompanied by an epidemiological study on the
      quality of care and life of the Italian thalassaemic population and on the
      acceptability and safety profile of the new preparation compared with the old
      one. METHODS: This was a two-period prospective survey of 867 patients (12% of
      the registered thalassaemic patient population) in a sample of centres
      representative of the different contexts of care. RESULTS: The majority of
      patients (81%) reported an overall positive opinion about the quality of care
      (median satisfaction score 7.4). Judgement was more critical among patients over
      15 years, unemployed, less compliant with chelation treatment and with higher
      mean serum ferritin levels. The co-morbidity profile did not appear to influence
      patients' satisfaction scores, but 21% of respondents associated great discomfort
      with the use of Desferal, which appeared in a multivariate analysis to be a
      strong predictor [odds ratio (OR) 2.15, 95% confidence interval (CI) 1.20-3.83]
      of negative perception. Quality of life was reported as fair or poor (score below
      6) by 21% of patients. Over a total of 29,066 infusions included in the
      comparison of the safety of the new versus the old preparation, the reported
      incidences of any adverse event (AE) were 51% versus 57%, respectively, and 8.2%
      versus 9.3% for severe AEs. Comparing the new with the old preparation, the
      adjusted relative risk of severe AEs was 0.79 (95% CI 0.65-0.96). CONCLUSION:
      While oral chelation therapies are still under evaluation, the overall quality of
      care and perceived quality of life of a representative sample of the Italian
      population of thalassaemic patients show that room for improvement depends more
      on the contexts of life and care than on strictly medical conditions.
      Comprehensive epidemiological surveillance is needed as a routine component of
      the care of this highly morbidity-burdened population to ensure timely
      appreciation of unmet needs and to assess the yield of innovative treatment
      schedules.

PMID- 11317482
TI  - Are there differences in the use of selective serotonin reuptake inhibitors and
      tricyclic antidepressants? A prescription database study.
AB  - AIM: The aim of the present study was to analyse the utilisation of
      antidepressants (ADs) and to compare the utilisation of the various ADs with
      special reference to duration of treatment courses. METHOD: From the Odense
      Pharmacoepidemiologic Database (OPED), all users of and prescriptions for ADs in
      the County of Funen, Denmark (about 470,000 inhabitants), were identified for
      each year from 1992 to 1997 (6 years). Duration of treatment courses was
      calculated for the first incident period of continuous use of one AD and was
      compared for the various ADs using Kaplan-Meiers survival statistics with log
      rank tests. Continuous use was defined as use of a minimum of one tablet per day.
      Furthermore, the proportion of users presenting only one prescription was
      determined for each AD. RESULTS: In total, 37,598 patients presented 392,524
      prescriptions during 1992-1997. The 1-year prevalence rose from 2.1% to 4.1% in
      1997 and the incidence was 1.3% in 1997. The 1-year prevalence increased with age
      up to 16.5% in 1997 for patients aged 90 years or older. Citalopram was the most
      used AD, but there were still a considerable number of patients commencing
      treatment with TCAs in 1997. Median duration of treatment courses was 196 days
      for TCAs versus 120 days for SSRIs (P < 0.0001). Duration of treatment courses
      increased with age. The proportion of users presenting only one prescription was
      22% for the SSRIs versus 33% for tricyclic antidepressants (TCAs). CONCLUSION:
      This study showed that the use of ADs continues to increase because of the
      increase in the use of the new ADs. There was, however, still a considerable
      number of patients who started on TCA treatment in 1997. For repeated
      prescriptions, TCAs were used for longer times than SSRIs. In the very old, there
      was an apparently inappropriate high use of ADs.

PMID- 11317483
TI  - Are users of lipid-lowering drugs at increased risk of peripheral neuropathy?
AB  - OBJECTIVE: To estimate the risk of peripheral neuropathy associated with use of
      lipid-lowering drugs. METHODS: Population-based dynamic cohort study based on
      data from general practices in the United Kingdom from 1991 to 1997. Three
      cohorts of individuals aged 40-74 years were identified: a cohort of 17,219
      persons who received at least one prescription for lipid-lowering drugs in the
      period; a second cohort of patients with a hyperlipidaemia diagnosis who had not
      been prescribed lipid-lowering drugs (n = 28,974) and a third cohort comprised of
      50,000 individuals from the general population. The incidence rates of peripheral
      neuropathy in the three cohorts were calculated and the relative risk of
      peripheral neuropathy in users of lipid-lowering drugs was compared with non
      users from the general population cohort. RESULTS: The incidence rate of
      idiopathic peripheral neuropathy in users of lipid-lowering drugs was higher
      [0.73 per 10,000 person-years, 95% confidence interval (CI) 0.01-2.62] than in
      the hyperlipidaemia non-treated cohort (0.40 per 10,000 person-years, CI 0.05
      1.46) and the general population cohort (0.46 per 10,000 person-years, CI 0.13
      1.18). The raised risk of idiopathic peripheral neuropathy in users of lipid
      lowering drugs was confined to current users of statins (relative risk 2.5, CI
      0.3-14.2). These figures suggest one excess case of neuropathy for every 14,000
      person-years of statin treatment. CONCLUSIONS: Because of the wide CIs, these
      results are inconclusive and should be interpreted with caution. However,
      although peripheral neuropathy as an adverse effect of the use of lipid-lowering
      drugs cannot be excluded, the magnitude of this untoward effect appears to be
      small.

PMID- 11317484
TI  - Analysis of the direct cost of adverse drug reactions in hospitalised patients.
AB  - The hospitalised patients in a cardiological hospital (Lille, France) over an 18
      month period were subjected to a prospective high-intensity adverse drug reaction
      (ADR) monitoring in order to assess the additional financial resource utilisation
      associated with ADRs and analyse the distribution of excess of cost according to
      ADR nature and therapeutic classes. Over 18 months, among the 16,916 hospitalised
      patients, 371 verified ADRs detected by self-report stimulated by a special unit
      of nurses and pharmacologists occurred in 336 patients with an overall ADR rate
      of 2.2%. This rate increased with age. The most common reactions were cutaneous
      events (24%), cardiovascular events (21%), metabolic disorders (12%), coagulation
      disorders (10%) and nervous system impairment (10%). The most common drug classes
      involved were cardiovascular agents (36%), contrast media (20%), drugs affecting
      blood clotting (13%) and anti-infectives (14%). Increased ADR-induced costs
      result especially from prolongation of length of stay and cost increase was
      evaluated at Euro 4150 per ADR. Among the 371 ADRs, 134 ADRs, which were
      significantly more severe, induced a prolongation of length of stay. Renal
      insufficiency and cardiovascular events were significantly over-represented in
      this sub-group. The most common ADR-inducing drugs associated with a prolongation
      of length of stay are cardiovascular agents and drugs affecting blood clotting.
      In contrast, cutaneous ADRs were significantly over-represented in the group of
      ADRs without prolongation of length of stay. The severity and substantial costs
      of ADRs in hospital justify investments to prevent these events. Nevertheless,
      only a portion of ADRs induces cost increases, suggesting that prevention efforts
      should focus on this limited category of ADRs.

PMID- 11317485
TI  - Seasonal variation of antibiotic and psycho-pharmacological drug prescriptions in
      a neuro-psychiatric hospital assessed by means of sine-wave models.

PMID- 11317486
TI  - [Brain plasticity].
AB  - The ability to undergo lasting changes of neuronal response properties i.e.
      plasticity, is one of the most important aspects of functioning of the nervous
      system. The paper reviews the plastic changes of adult mammalian cerebral cortex.
      It describes compensatory plasticity induced by peripheral denervation and
      compensatory plasticity following central trauma. Neuronal mechanisms of cortical
      neuroplastic changes are presented and the common rules of all forms of cortical
      modifications are discussed. The paper stresses the therapeutic value of training
      in various sensory modalities for corrections of functional maladaptation of
      cortical maps and compensation of function after stroke.

PMID- 11317487
TI  - [Long-term prognosis in young adults after a cerebral ischemic episode].
AB  - To asses long term prognosis in young adults with cerebral ischaemia a follow up
      study was performed. Eighty-four patients aged 18 to 45 years with the diagnosis
      of the first-ever ischaemic stroke or TIA were followed up. Four of them (4.8%)
      died within the first four weeks of cerebral ischaemia onset. Information about
      all but one patient (98.75%) who survived the first episode of cerebral ischaemia
      was obtained. The follow up time lasted 4 months till 8 years (mean 52 months +/-
      20 months). Three of the patients died during the follow up (all--vascular
      deaths), twenty one others experienced second cerebral ischaemia one month to 80
      months after the first one. Among the patients with first-ever ischaemic stroke
      the calculated incidence of vascular death or recurrent stroke in the patients
      who survived the first episode was 5.6% per year, and after 24 months--10.9%.
      Twenty-eight day mortality rate was in that group 5.6%. Twenty-eight day
      mortality rate, was in our group similar to the data from the literature, but
      recurrent stroke and vascular deaths appeared in our material twice as often as
      in the literature. It could be the effect of lifestyle and socioenvironmental
      determinants.

PMID- 11317489
TI  - [Knowledge of stroke problems among adults in Poland].
AB  - An inquiry questionnaire was given to 180 adults without a history of stroke. The
      questions concerned the problem of stroke. The responders were aged from 15 to 82
      years (mean 48 years). They were asked about risk factors for stroke, symptoms
      preceding stroke, behaviour of stroke witnesses. A correct definition of stroke
      was given by 86.7% of the responders. Only a small proportion of them knew risk
      factors for stroke (27.8% knew that one of them was hypertension, 6.1% gave
      smoking, 4.4% diabetes as risk factors). Although 93.9% knew that in face of
      stroke physician or ambulance service should be called, 6.1% thought that it
      would be sufficient to lie down or take paracetamol. The inquiry showed that the
      knowledge of risk factors for stroke is insufficient in the Polish adult
      population who not yet had cerebrovascular disturbances. It seems advisable to
      deliver an education programme in mass media on stroke prevention and its
      management in case of its development.

PMID- 11317488
TI  - [How do general practitioners proceed on initial contact with patients after
      cerebrovascular ischemia?].
AB  - The reported analysis of an inquiry study of first-contact physicians was carried
      out for establishing how the manage cases of ischaemic stroke and transient
      ischaemic accident (TIA). The inquiry questionnaire containing questions related
      to the management of these patients and outpatient diagnosis of patients after
      stroke or TIA was sent to general practitioners in 4 regions of the country. The
      form was returned by 159 out of 300 physicians, mostly those working in towns
      (90.6%). From 53.5% to 64.8% of physicians referred patients with symptoms
      suggestive of stroke to hospitals, less often were referred those with vision
      disturbances. Antiplatelet drugs were prescribed to patients with cerebral
      circulation disturbances by only 12% to 20.3% of the physicians. Only 46.8% of
      the physicians used anticoagulants as secondary prevention after cerebral
      embolism from the heart. In patients treated with anticoagulants INR was checked
      every 2 weeks by 50.9% physicians. Only 42.8% of the physicians referred the
      patients for USG examination of neck arteries. The analysis showed that too few
      first-contact physicians referred stroke cases to hospital and too few prescribed
      antiplatelet drugs for TIA. Anticoagulants were used insufficiently for secondary
      prevention after cerebral embolism from the heart. There is much to do in stroke
      cases for management and prevention.

PMID- 11317490
TI  - [Increased percentage of "double phenotype" form T lymphocytes in blood of
      patients with multiple sclerosis].
AB  - We studied the percentage of double positive (CD4+CD8+) form of T-cells in a
      group (total 77) multiple sclerosis (MS) patients, measured by means of
      monoclonal antibodies anti-CD3, CD4/FITC, CD8/RPE and flow cytometry FACScan
      (Becton Dickinson). In our study we have shown that the percentage of the double
      positive T cells is higher (p < 0.05) in the peripheral blood of patients with
      acute exacerbation of MS (n = 21), and in the course of chronic progressive MS (n
      = 27) comparing to MS remission (n = 29) and other neurological diseases (n = 25)
      groups. In the study we have shown that the percentage of double positive T-cells
      in peripheral blood depends mainly on disease activity.

PMID- 11317491
TI  - [Genotype-phenotype correlation in hereditary motor-sensory neuropathy type IA
      associated with duplication in chromosome 17p11.2-12].
AB  - Results of clinical, electrophysiological and morphological examination, were
      presented in 19 patients from 8 families with hereditary motor-sensory neuropathy
      type I (HMSN type I) with 17p11.2-12 duplication (i.e. CMT IA). The course of the
      disease was rather mild, slowly progressive. Generalized demyelinating lesion of
      peripheral nerves was found on EMG examination, with median nerve conduction
      velocity between 10-20 m/s and very prolonged F wave latency. Sural nerve biopsy
      was characteristic of chronic demyelinating process. Phenotypic characteristics
      of our HMSN type I patients shows clinical, electrophysiological and
      morphological homogeneity, however there are some data from literature indicating
      possibility of intrafamilial and interfamilial variability.

PMID- 11317492
TI  - [Psychological profile of patients with psychogenic pseudoepileptic seizures].
AB  - Depending on the accepted definition of the nature of psychogenic pseudoepileptic
      seizures various values of their prevalence are reported in the literature from
      5% to over 33% of cases referred to epilepsy treatment centres. According to our
      knowledge, in Poland these seizures occur in several thousand young individuals
      (mean age 25 years). The psychological determinants of these psychogenic seizures
      remain not clear. The purpose of the reported study was a psychological analysis
      of personality profiles of patients with psychogenic pseudoepileptic seizures and
      epileptic seizures using the results of Minnesota Multiphasic Personality
      Inventory test for the assessment of conversion as a possible mechanism of the
      occurrence of psychogenic pseudoepileptic seizures. Using long-term video-EEG
      monitoring the studied subjects were divided into two groups: group I of 30
      subjects (25 women and 5 men) with exclusively psychogenic pseudoepileptic
      seizures, and group II of 27 subjects (23 women and 4 men) with exclusively
      epileptic seizures. Both groups were subjected to MMPI test. The averaged
      profiles of these groups differed in the level of hypochondria (Hs--p < or =
      0.001) and hysteria (Hy--p < or = 0.005) statistically significantly, and were
      much higher in patients with psychogenic pseudoepileptic seizures than the
      depression parameter (D) statistically significantly (p < or = 0.001). Patients
      with epilepsy had the highest values of depression parameter (D), while Hs and Hy
      were statistically significantly lower (p 0.01). The analysis in subscales
      additionally confirmed the role of conversion in pseudoepileptic seizures.

PMID- 11317493
TI  - [Epidermal growth factor expression in brain neoplasms].
AB  - Epidermal growth factor (EGF) influences the cell by activation of its specific
      cell receptor (EGFR). It is regarded as one of the most effective mitogenic
      factors and plays a role in carcinogenesis. The aim of this study was the
      assessment of EGF expression in different types of cerebral neoplasms and
      searching for its correlation with histopathologic features of malignancy and
      presence of peritumoral oedema. Sixty seven samples of brain tumours were
      examined. Among them were 17 meningiomas, 34 gliomas and 16 metastases.
      Expression of EGF was estimated by a radioimmune assay. The authors found the
      presence of EGF in all types of tumours. No correlation was found between
      expression of EGF and histopathological signs of tumour malignancy, although a
      tendency appeared towards a higher level of that factor in anaplastic tumours.
      Also, no correlation was found between EGF and peritumoral oedema.

PMID- 11317494
TI  - [Visual system function in patients after surgery for intracranial tumors].
AB  - Visual function was studied in patients after operations for brain tumours. The
      study group comprised 7 cases. Visual acuity, field of vision by kinetic and
      static methods and visual evoked potentials were studied before and after
      operations. The follow up time was from 1 to 51 months, mean 20 months. In all
      patients decreased visual acuity, visual field defects and VEP abnormalities were
      found, before operation. The first control examination after operation showed
      improvement of visual acuity in 2 cases after removal of pituitary tumours, and
      worsening of vision in all the remaining ones. In two cases of tumours spreading
      to the basis of the frontal lobe blindness of one eye developed. Static and
      kinetic perimetry showed in all cases enlarged visual field defects. VEP
      confirmed that removal of pituitary tumours compressing visual tract can improve
      vision: P100 amplitudes increased and latencies become shorter. Further VEP
      improvement occurred even 6-20 months after achieving of good visual acuity. No
      improvement of vision developed if the visual pathway had been damaged during the
      operation. CONCLUSIONS: Pituitary tumours can be removed without damage to the
      surrounding structures and vision can improve after that. Meningiomas and gliomas
      lying in immediate vicinity of optic nerves and their chiasma or growing out from
      them are usually large and often their removal is associated with damage to the
      visual pathway leading to visual field defects to blindness. The assessment of
      vision should be based on static and kinetic perimetry and visual evoked
      potentials (VEP) since these methods are mutually complementary and only their
      comparison provides a full result.

PMID- 11317495
TI  - [Use of transpedicular fixation in treatment of thoraco-lumbar spinal injuries].
AB  - In Orthopaedic University Department in Lublin in years 1993-1998 39 patients
      with thoraco-lumbar spine injuries were treated including 34 fractures and 5
      luxations. All of them were treated by surgery. Complete neurological palsy
      (Frankel A) occurred in 16 patients. Grade E on Frankel scale e.g. no
      neurological symptoms was in 2 cases. The operations consisted of wide
      laminectomy with interpedicular joints resection. It gave chance to mobilise the
      dural sac with its contents. In this situation it was possible to remodel the
      anterior wall of spinal canal by removal of fractured bony pieces from vertebral
      body or fibroid remnants of damaged disc. Injured segments of the spine were
      stabilized by Kluger's fixateur. In 20 cases reduction of vertebral body fracture
      and filting of bone loss by autogenic spongiosa grafts from iliac crest as
      proposed by Daniaux was done. In 6 patients posterior interbody spondylodesis was
      done also with iliac crest grafts. In 9 patients who had only reduction of
      injured segments, without vertebral body reconstruction and spondylodesis loss of
      correction occurred after fixateur removal. In 3 patients fatigue break of screws
      or stabilizing rods developed. It happened 12-16 months after surgical procedure.
      In patients with primary complete neurological palsy from the level of injury
      (Frankel A) no symptoms of function improvement appeared higher than one grade in
      Frankel's scale.

PMID- 11317496
TI  - [Etiologic and diagnostic factors of psychogenic pseudo-epileptic seizures].
AB  - The term psychogenic pseudoepileptic seizures (or psychogenic non-epileptic
      seizures-NES) generally refers to episodes of psychological origin that resemble
      epilepsy but without underlying epilepsy. The diagnosis of pseudo-epileptic
      seizures is confirmed in 5-33% of patients that are considered to suffer from
      refractory epilepsies. Making a correct diagnosis in patients presenting with
      attack disorders is sometimes very difficult. However, the best way to establish
      differential diagnosis of epileptic and pseudoepileptic seizures is to apply long
      term video EEG monitoring. Triggering a seizure by means of placebo
      administration or suggestion to start or stop seizure can be also a helpful
      method in differential diagnosis. Over the last decade epileptologist have been
      paying increasing attention to the Minnesota Multiphasic Personality Inventory
      (MMPI) scales in describing or distinguishing real epileptic seizures vs. non
      epileptic attacks. The results of the study may have practical implications for
      neurological and epilepsy centres, and for improving clinical knowledge and allow
      to establish aetiological classification of psychogenic pseudoepileptic seizures.

PMID- 11317497
TI  - [Analysis of intracranial pressure signals using artificial neural networks].
AB  - Intracranial pressure (ICP) is influenced by an array of predictable and
      unpredictable factors. Statistical modelling of this signal has only limited
      applicability because of the significant load of stochastic components. We tested
      the efficiency of an alternative approach, based on the methodology of artificial
      neural networks (ANNs) in the on-line prediction of future values of ICP and in
      the classification of signal properties. Satisfactory accuracy of forecasting was
      achieved with the ANNs for a 3-minute prediction horizon, while the prediction
      quality with autoregressive models of statistical origin was proved
      unsatisfactory. The results obtained with the ANNs were further improved when
      signal pre-processing with wavelet transform was employed. Nevertheless, even
      with the ANN methodology, no sudden breakdowns in the ICP signal (which in this
      respect might be compared to a "catastrophe") can be forecast with any practical
      applicability. We therefore applied two ANN algorithms, oriented at
      classification and discrimination of the global properties of the ICP signal. The
      neural network was expected to discriminate those sets of signal properties,
      which were assumed to correspond to certain clinical conditions of the patient.
      In a "dynamic pattern classification" the network was presented with several
      sections of ICP records. This was combined with information about the assignment
      of a given record to one of four arbitrary classes of danger. In this mode no
      data pre-processing was carried out, in contrast to our second approach, in which
      the signal was pre-processed with statistical analyses and only these
      intermediate coefficients were fed to the ANN classifier. The results obtained
      with both classification methods at their present stage of training were similar
      and approximated to a 70% rate of judgements consistent with expert scoring.
      Nevertheless, the method based on the assessment of global parameters of the ICP
      record seems more promising, because it leaves the possibility of extending the
      set of training data by information from other diagnostic modalities. The study
      aims towards the development of a pseudo-intelligent computer expert system,
      which has would be taught salient links between data extracted from the ICP
      signal and higher- order data, which contributed to the expert score. Hence the
      system would be able to make decisions on the basis of a reduced set of input
      information, available from a standard monitoring modality.

PMID- 11317498
TI  - [Efficacy of the newest ultrasonographic techniques in intraoperative
      neurosurgical diagnosis].
AB  - The contemporary neurosurgery requires efficient methods of intraoperative image
      guidance. Among some expensive techniques the rather cheap intraoperative
      ultrasound has been widely accepted in the last decade. The aim of the study is
      to estimate the efficacy of this technique in the intraoperative evaluation of
      the different kinds of brain lesions. The authors illustrate it with some
      ultrasonic images presented in comparison to the images obtained from the
      preoperative CT or angiography. B-mode ultrasound has proven to be extremely
      useful for localizing subcortical rather than deep-seated brain tumours, cysts,
      abscesses as well as intraparenchymal haematomas. The advantages were
      particularly evident when searching for tumours that were not visible on brain
      surface. Its use for guidance in cyst or abscess aspiration, as well as
      usefulness in tumor vascularization estimations (using Power Doppler mode) is
      outlined. Ultrasound B-mode Color or Power Doppler sonography with high
      resolution probes offers new possibilities of intraoperative control of
      neurovascular procedures--either in the localization of small arterio-venous
      malformations (AVMs) and feeders estimation or for the evaluation of proper clip
      application in the aneurysm surgery.

PMID- 11317499
TI  - [Guillain-Barre syndrome in a patient with primary sicca syndrome].
AB  - At the age of 23 the patient showed the first signs of dryness syndrome. Those
      symptoms developed progressively and during a few years primary Sjogren syndrome
      was noted. In the 37th year of life suddenly the patient developed very severe
      Gullian-Barre syndrome with involvement of the peripheral and central nervous
      system and with a considerable autonomic component. After treatment the patient
      improved, however mild symptoms of central and peripheral nervous system
      destruction remained. Those symptoms are still present and the patient is under
      the care of the Neurology and Rheumatology Clinic.

PMID- 11317500
TI  - [Endovascular treatment of internal carotid artery giant aneurysm by embolization
      of the parent artery using a detachable balloon].
AB  - A giant, unclippable right ICA aneurysm located partially intracavernously is
      reported with neck deriving at C3 level. The aneurysm caused optic chiasm
      compression, progressive left eye vision loss and exophthalmus as well as
      persistent headache. The presence of the aneurysm was first found in CT and
      confirmed by angiography. After having performed the temporary occlusion test of
      right ICA the ICA was permanently occluded with a detachable balloon. Control
      angiography showed complete occlusion of right ICA and no opacification of the
      aneurysm sac from vertebral and left carotid arteries.

PMID- 11317501
TI  - [Rasmussen syndrome--indications for surgical treatment of refractory epilepsy:
      report of two cases].
AB  - AIM: Presentation of two cases of children with Rasmussen's encephalitis, treated
      by functional hemispherectomy. Two boys aged 4 and 6, with a typical clinical
      course, typical findings in CT and MRI scans and characteristic pathologic
      changes in brain specimens. In both cases was performed functional
      hemispherectomy. RESULTS: Immediate cessation of seizures in the immediate
      postoperative period (Engel class I and II). Later, in a 4-months' follow-up
      period, a worthwhile improvement in psychomotor development and social
      functioning was noted. Up-to date opinions published in available literature,
      related to pathogenesis and treatment modalities of Rasmussen's encephalitis are
      presented. CONCLUSIONS: 1) Rasmussen's encephalitis is a definite nosologic
      entity, leading to drug-resistant epilepsy and a progressive psychomotor
      deterioration; 2) functional hemispherectomy is a viable alternative, which
      should be considered in the treatment of Rasmussen's encephalitis; 3) Functional;
      hemispherectomy, in spite of it's aggressiveness, is a relatively safe procedure;
      4) in the follow-up time of 4 months, the results are promising.

PMID- 11317502
TI  - [Posttraumatic ectopic calcification as an additional pathologic factor of
      brachial plexus palsy].
AB  - The authors describe a case of a 54-year-old male, who was attacked with a broken
      bottle and wounded in left supraclavicular region. No neurologic deficit was
      observed immediately after injury. Some days later signs of upper trunk brachial
      plexus palsy were detected. Gradually symptoms of the Erb syndrome have
      developed. He was operated on 5 months after injury. During surgery no
      discontinuity of the brachial plexus was found. Unexpectedly there were an inner
      scar and free bony fragment compressing the upper trunk and the suprascapular
      nerve. Both the scar and bony fragment were carefully dissected and removed.
      Result of surgery: pain relief, restoration of normal sensation and partial
      restoration of biceps function.

PMID- 11317503
TI  - [Tethered cord syndrome in adults].
AB  - The authors present a description of three patients in whom symptoms of spinal
      cord injury developed late after opening of the dural sac of the spinal canal.
      The material comes from two female and one male patients of age 37-47 years. In
      the first case the symptoms included increased paraesthesia, pain, paraparesis
      and sphincter disorders, which appeared 16 years after stab wound of meninges and
      the spinal cord at Th10. In the second patient, operated on for myelomeningocele
      at L3-4 at the age of five, sphincter disorders, trophic changes of feet and
      paraparesis appeared. The third patient was operated on for intra- and
      extramedullary lipoma at Th9-12. Seven months after the operation symptoms of
      sphincter disorders, pain, paraesthesia and paraparesis developed. The MR
      examination showed in all patients an adhesion of the posterior or posterolateral
      surface of the spinal cord with the dura mater at the sites of injury, which was
      confirmed intraoperatively. An operative treatment improved the clinical state.
      The tethering of the cord by the scar was the cause of a non-physiological
      stretching of the spinal cord on flexion of the body and head. It led to spinal
      circulation disorders and symptoms of myelopathy. It has been observed that the
      onset of the symptoms is often caused by sudden stretching of the spinal cord
      during fall or intense physical exercises. In such cases operative release of the
      spinal cord from the adhesion is a method of choice.

PMID- 11317504
TI  - [Spontaneous intracranial epidural accumulation of air in a patient with
      excessive skull pneumatization].
AB  - We report a rare case of spontaneous epidural accumulation of air in the
      occipital region resulting from an unusual hyperpneumatization of the cranium in
      a 37-year-old miner. For suspected subarachnoid haemorrhage the patient was
      admitted to neurological department. Performed computed tomography (CT) revealed
      extensive hyperpneumatization of the cranium, involving also the upper part of
      the cervical vertebral column, and epidural pneumocephalus. To the authors
      knowledge, so much pneumatization of the cranium seems to be very rare and when
      present, however, can cause spontaneous pneumocephalus. Based on the two years
      follow-up of this patient, conservative therapy showed to be sufficient for him,
      despite this, we have suggested him periodically perform CT of the head.

PMID- 11317505
TI  - Infinite variety and complexity: an urgent challenge for psychoanalysis.

PMID- 11317506
TI  - Psychoanalysis at the end of the third millennium.

PMID- 11317507
TI  - Symptoms, signals, affects: psychotherapeutic techniques with dissociative
      patients.

PMID- 11317508
TI  - Postmodern tools for the clinical impasse.

PMID- 11317509
TI  - An analyst's uncertain knowledge: the case of a suspected rapist.

PMID- 11317510
TI  - Psychodynamic psychotherapy and executive coaching--overlapping paradigms.

PMID- 11317511
TI  - Empirical evidence and the health of psychoanalysis.

PMID- 11317512
TI  - Notes on Bion's "memory and desire".
AB  - Memory and desire, along with understanding and preconception, are to be
      abandoned (really, suspended) for the analyst to be ever open to unexpected
      emerging from the analysand's unconscious. The discipline that Bion suggests
      allows the analyst to be open to his/her own native feelings as an emotion
      receptor and analytic instrument.

PMID- 11317513
TI  - The dialectics between biological and cultural evolution.

PMID- 11317514
TI  - Application of Ledoux's neurobiological findings in treating anxiety disorders.

PMID- 11317515
TI  - Reality.

PMID- 11317517
TI  - Effects of intra-arterial administration of prostaglandin E1 on rat cremaster
      muscle microcirculation.
AB  - In plastic and reconstructive surgery, postoperative drug therapy with
      prostaglandin E1 (PGE1) has been widely used to prevent flap necrosis and to
      extend flap surviving area. In the present study, we assessed the effects of
      intra-arterial administration of PGE1 on microcirculation. The left cremaster
      muscle of male Wistar rats were used to measure microcirculatory hemodynamic
      parameters. The values of internal vessel diameter and erythrocyte velocity were
      measured by using the confocal laser-scanning microscope (CLSM) system and
      fluorescent dyes. The blood flow rate was calculated from measured internal
      vessel diameter and erythrocyte velocity. Internal vessel diameter and flowing
      erythrocytes were satisfactorily visualized by using the CLSM system. The blood
      flow rate of arteriole, venule and capillary were dose dependently increased by
      the intra-arterial administration of PGE1 from the minimum dose of 0.01
      ng/kg/min. It is suggested that the intra-arterial administration of PGE1 is a
      more effective way of postoperative drug therapy than intravenous injection for
      flap surgery.

PMID- 11317518
TI  - Comparison of plasma component levels in four strains of female mice with
      different mammary tumour potentials.
AB  - Based on the importance of general metabolic activity to mammary tumourigenesis,
      plasma component levels were examined at 6 and 10 months of age in female virgin
      mice of four strains, which in mammary tumour potential, rank in the descending
      order of SHN, GR/A, SLN and C3H/He. The plasma aspartate aminotransferase level
      elevated from 6 to 10 months of age in the SHN and GR/A, but not in the SLN and
      C3H/He strains. The total bilirubin level was higher in the former two strains
      than the latter two at both 6 and 10 months. The blood urea nitrogen level was
      highest in SHN. C3H/He had the lowest plasma levels of these components as well
      as amylase at both ages. The results indicate the signifcance to the mammary
      tumourigenic potential of plasma levels of certain components related to general
      metabolic activity.

PMID- 11317516
TI  - Effects of human recombinant erythropoietin on differentiation and distribution
      of erythroid progenitor cells on murine medullary and splenic erythropoiesis
      during hypoxia and post-hypoxia.
AB  - Hemopoietic cells, the extracellular matrix, growth factors and the
      microenvironment are involved in the regulation of hemopoiesis. Although the
      regulation of erythropoiesis is well understood at the cellular level in vivo and
      in vitro, the role of hemopoietic sites of erythroid progenitors production has
      not been well defined in both steady state conditions and in stress
      erythropoiesis. In this study we examined the qualitative erythroid
      differentiation and quantitative changes of the erythroid progenitors in
      different erythropoietic organs during erythropoiesis of stress in a hypoxia
      induced polycythemia and post-hypoxic changes in a mice model. Chronic
      intermittent exposure to hypobaric hypoxia induced polycythemia in mice and the
      post-hypoxic period was characterized by total suppression of erythropoiesis. The
      number and distribution in hemopoietic sites of Immature Erythroid Burst (BFU
      EI), Mature Erythroid Burst (BFU-EM) and Erythroid Colony Forming Units (CFU-E)
      was evaluated in bone marrow and spleen of hypoxic and post-hypoxic mice after
      removal from the chamber. The number of BFU-EI and CFU-E, was evaluated in both
      femoral bone marrow and spleen of ex-hypoxic polycythemic mice, at two times
      intervals after the end of hypoxia. We found that in both bone marrow and spleen,
      the kinetics of the CFU-E pool was characterized by a sharp fall from above
      normal to lower than normal levels. BFU-EM increased from normal to higher than
      normal levels. These results have been correlated with both erythropoietin (EPO)
      and the erythropoietic activity. The results show that EPO levels largely control
      both the differentiation and the amplification of the CFU-E pool and they suggest
      that EPO may acts as a "survival factor" at the CFU-E level and/or increase the
      flow of cells from BFU-E to CFU-E. After the termination of the period of hypoxia
      and during post-hypoxia there was a reduction in EPO production which
      subsequently caused a depletion of the CFU-E population, indicating that the size
      of the CFU-E pool is EPO-dependent. After the injection of 1U of recombinant
      human erythropoietin (rHuEPO) the size of that pool was increased and the pool of
      BFU-EI was decreased. It is noteworthy that our studies show that the spleen
      functions as a large reservoir of erythroid precursors for hypoxia-induced stress
      erythropoiesis.

PMID- 11317519
TI  - Diverse biological activity of polycaphenol.
AB  - Millimolar concentrations of alkaline extract of Cacao husk (polycaphenol) were
      more cytotoxic to human oral tumor cells (human oral squamous cell carcinoma HSC
      2, human salivary gland tumor HSG), than to human gingival fibroblast (HGF),
      suggesting its tumor-specific action. Polycaphenol enhanced the radical intensity
      and cytotoxic activity of vitamin K3 more effectively than that of sodium
      ascorbate (vitamin C). Polycaphenol effectively scavenged the superoxide anion,
      produced by the hypoxanthine-xanthine oxidase reaction, indicating bimodal
      (prooxidant and antioxidant) action of polycaphenol. Polycaphenol inhibited the
      cytopathic effect of HIV (human immunodeficiency virus) infection in MT-4 cells,
      to a comparable extent as that achieved by lignin. Pretreatment of mice with
      polycaphenol protected them from lethal infection of Eschericia coli. These data
      suggest the medicinal efficacy of polycaphenol.

PMID- 11317520
TI  - Effects of naturally occurring glucosides, solasodine glucosides, ginsenosides
      and parishin derivatives on multidrug resistance of lymphoma cells and leukocyte
      functions.
AB  - Solamargine, solasonine, ginsenosides and parishin-related compounds were
      investigated for their effects on mdr efflux pump of lymphoma cells, and their
      effects on T cell proliferative assays and cell mediated immune functions,
      antibody-dependent cellular cytotoxicity (ADCC) and natural killer (NK) cell
      activity of human peripheral mononuclear cells. Solamargine and solasonine were
      the only drugs which inhibited all of the tested immune functions; however,
      ginsenoside Rc and Rd enhanced T cell proliferative assays and marginally
      increased the NK cell activity. The majority of the compounds were not able to
      reverse the multidrug resistance of mouse lymphoma cells. However, ginsenosides
      Rc, Rd and parishin C were able to moderately reduce the activity of the efflux
      pump. Parishin, parishin C and crude extract significantly enhanced the ADCC
      reaction.

PMID- 11317521
TI  - Establishment and characterization of a new human prostatic cancer cell line:
      DuCaP.
AB  - BACKGROUND: The lack of appropriate, clinically relevant, cell-based model
      systems has limited prostate cancer research and the development of new
      therapeutic modalities. Here we report the isolation and characterization of a
      new adherent prostate cancer cell line, derived from the dura mater of a cancer
      patient. METHODS: Prostate cancer tissue was harvested at autopsy from a
      metastatic lesion to the dura mater of a patient with hormone refractory prostate
      cancer. This tissue was xenografted into SCID mice and later harvested and plated
      on tissue culture dishes. For characterization, soft agar clonegenic assay, in
      vivo xenograft growth, in vitro doubling time, karyotype analysis,
      immunocytochemistry for cytokeratin-18, androgen receptor, and PAP (prostatic
      acid phosphatase) expression, RT PCR for PAP, PSMA (prostate specific membrane
      antigen), expression and northern and western blot analysis to determine
      expression of Rb and p53, were performed. RESULTS: DuCap grows in vitro (passage
      55), forms colonies in soft agar, produces tumors in SCID mice (xenograft passage
      12), and is androgen sensitive. DNA content was hypertriploid. PSA was detected
      in mouse serum and media. Cells were AR, PAP and cytokeratin-18 positive by
      immunocytochemistry. PSMA and PAP were detected by RT-PCR. AR, P53, and Rb were
      expressed in Northern blot analysis. P53 protein was detected in Western blot
      analysis but Rb protein was not. CONCLUSIONS: This cell line exhibits many
      phenotypic characteristics of clinical prostate carcinoma, including expression
      of PSA, PSMA, PAP and AR.

PMID- 11317522
TI  - VCaP, a cell-based model system of human prostate cancer.
AB  - OBJECTIVES: We report the isolation and characterization of a novel prostate
      cancer cell line derived from a vertebral metastatic lesion, Vertebral-Cancer of
      the Prostate (VCaP). METHODS: Prostate cancer tissue was harvested at autopsy
      from a metastatic lesion to a lumbar vertebral body of a patient with hormone
      refractory prostate cancer. This tissue was aseptically xenografted into SCID
      mice and later harvested and plated on tissue culture dishes. For
      characterization, soft agar clonegenic assay, in vivo xenograft growth, in vitro
      doubling time, karyotype analysis, immunocytochemistry for cytokeratin-18
      expression immunochemistry for PSA (prostate specific antigen), RT PCR for PAP
      (prostatic acid phosphatase) and northern blot and western blot analysis to
      determine expression of Rb and p53, were performed. Androgen receptor expression
      was measured by transient transfection with a luciferase reporter construct.
      RESULTS: VCaP cells are immortal in vitro and can be passaged serially in vivo.
      They express large quantities of prostate specific antigen (PSA). This cell line
      also expresses prostatic acid phosphatase (PAP), cytokeratin-18 and the androgen
      receptor, and is androgen sensitive in vitro and in vivo. CONCLUSIONS: This cell
      line was derived from a metastatic tumor to the vertebrae of a prostate cancer
      patient. It exhibits many of the characteristics of clinical prostate carcinoma,
      including expression of PSA, PAP, and AR. We believe that VCaP will be a useful
      addition to the existing models of prostate cancer, and enable more advanced
      study of the mechanisms of prostate cancer progression and metastasis.

PMID- 11317523
TI  - FHIT gene expression in human urinary bladder transitional cell carcinomas.
AB  - BACKGROUND: Our purpose was to investigate the expression of FHIT (Fragile
      Histidine Triad) gene product in a series of 110 urinary bladder TCCs, and its
      eventual relationship with histological grade, clinical stage, recurrences and
      patients' survival. MATERIALS AND METHODS: We performed immunohistochemistry in
      archival material of formalin-fixed, paraffin-embedded tissues, using the anti
      Fhit antibody and the Streptavidin-biotin peroxidase method. RESULTS: In 30 out
      of 110 cases (27.27%) Fhit protein was absent whereas in 32 cases (29.08%) it was
      abnormally expressed. In 48 cases (43.63%) Fhit protein was diffusely expressed
      in all tumor cells. A statistically highly significant correlation (p < 0.001)
      was noticed between Fhit protein absence or reduction and clinically advanced
      tumors. Conversely, abnormal Fhit protein expression was not associated with age,
      histological grade, tumor size, number of recurrences, and clinical outcome in
      terms of patients' survival. CONCLUSIONS: These results confirm that FHIT gene
      inactivation is a late event in urinary bladder carcinogenesis. Fhit protein
      reduced expression or complete absence correlates with advanced clinical stage of
      the disease, and does not seem to correlate with tumor recurrences and patient
      survival.

PMID- 11317525
TI  - Intracranial cysticercosis: an effective treatment with alternative medicines.
AB  - The purpose of this study was to demonstrate the cysticidal activities of Ruta
      graveolens and calcium phosphate in fractional dilutions as a completely new
      approach for the treatment of neurocysticercosis in humans. These two homeopathic
      medicines when given to patients with neurocysticercosis have cured the infection
      in 25 subjects (69.4%) from a total of 36 patients. Our preliminary results
      indicate that Ruta graveolens in combination with calcium phosphate must be
      considered to be a potent cysticidal agent with very little or no side effects.

PMID- 11317524
TI  - Invasion and metastasis: the expression and significance of matrix
      metalloproteinases in carcinomas of the lung.
AB  - Structural changes in the extracellular matrix (ECM) are necessary for cell
      migration during tissue remodeling and tumor invasion. The matrix
      metalloproteinases (MMPs) and their inhibitors have been shown to be critical
      modulators of ECM composition and are thus, crucial in neoplastic cell invasion
      and metastasis. Expression of MMP-2, -3, -9, -10, and -13 was investigated in
      human lung adenocarcinomas employing an indirect alkaline phosphatase conjugated
      immunocytochemical technique. Evaluation of the results was based on (a) the
      percent of neoplastically transformed cells/surrounding stroma that reacted
      positively and (b) a measure of staining intensity [graded from A (highest) to
      D]. The two forms of stromelysin, MMP-3 and -10, share 82% sequence homology, but
      exhibit differences in cellular synthesis and inducibility by cytokines and
      growth factors in vitro. Strong overall expression of MMP-3 and -10 was found in
      lung adenocarcinomas, especially in the ECM adjacent to blood vessels. Positive
      immunoreactivity could be seen for these two MMPs in the ECM surrounding over 90%
      of the neoplastically transformed cells (++++), and the staining intensity was
      also the strongest possible (A,B). Focal (+), high intensity (A,B) staining could
      be detected for MMP-2, -9, and -13. Thus, it seems that the stromelysins are
      involved in the generalized growth and expansion of the neoplastic cell mass,
      while MMP-2, -9 and -13 are involved in the neoangiogenic and focal clonal
      selection and expansion phenomena associated with in situ tumor progression,
      invasion of the microvasculature, and metastasis.

PMID- 11317527
TI  - [Biotherapy of cancer and protease inhibitors].

PMID- 11317526
TI  - [Stereotaxic biopsy of non-palpable breast neoplasms with the ABBI system
      (USSC)].
AB  - The study was concerned with application of the stereotactic automated surgical
      biopsy breast with the ABBI (USSC) device for verification of non-palpable breast
      lumps. It included 13 females, aged 34-72 (mean age--54) and lasted 6 months
      (1999). Microcalcinates were detected in 3 (22.8%), local cordlike tissue
      structures--3 (22.8%), focal shadows--7 (53.2%). Lesion size: (5 mm (16%), 5.1-10
      mm (25%) and 10.1-20 mm (59%). Malignancy was diagnosed in 3 cases (22.8%), dia.
      7-10 mm; atypical ductal hyperplasia--2 (8.3%), and miscellaneous benign
      pathology--53.2%. Adequate removal of lesions was histologically confirmed in all
      cases. The procedure was carried out with ambulatory monitoring, under local
      anesthesia, and lasted 1.5 hrs. No complications were reported. The cosmetic
      results were good; no analgetics were dispensed. The ABBI system proved an
      effective means of stereotactic surgical biopsy of the breast because it removed
      the entire radiologically-suspicious site as a complete tissue preparation. It
      provided all histological data without crushing or segmenting the preparation.
      Since tissue texture and, particularly, the preparation edges remained intact,
      the latter could be examined too, if needed. All this ruled out inaccurate
      interpretation, repeat biopsy and unjustified lumpectomies.

PMID- 11317528
TI  - [Tamoxifen--"golden standard" in the treatment of patients with early breast
      cancer].

PMID- 11317529
TI  - [The potential of capecitabine (Xeloda) in the treatment of disseminated solid
      tumors].

PMID- 11317530
TI  - [Cardiotoxicity of antineoplastic anthracycline antibiotics and prevention by
      cardioxane (Dexrazoxane) in clinical practice].

PMID- 11317531
TI  - [Markers of bone remodeling: general concepts and clinical significance for
      skeletal lesions in oncologic patients].

PMID- 11317532
TI  - [Malignant tumors in the overall morbidity of the population in Saint
      Petersburg].

PMID- 11317533
TI  - [Risk factors for bone marrow involvement in Hodgkin's disease].
AB  - The significant factors of risk for bone marrow involvement in Hodgkin's disease
      included age over 40 yrs, such unfavorable histological features as lymphoid
      exhaustion and nodular sclerosing stage II, symptoms of intoxication, an ESR of
      more than 50 mm/h, increased fibrinogen (> 5.0 g/l), blood-plasma alkaline
      phosphatase (> 130 units), leukocyte concentration (> 10,000 per min) and
      decreased hemoglobulin (< 100 g/l). Despite the reliable correlation between bone
      marrow involvement and said factors, relevant data did not provide a similarly
      reliable basis for accurate prognosis of tumor dissemination. However, our
      findings pointed to two categories of Hodgkin's disease patients characterized by
      minimal risk of tumor dissemination--patients under 20, with stage I-II AB and
      IIIA tumors,--and patients with similar tumors and such favorable histological
      patterns of major pathology as high lymphocytic ratio and nodular sclerosing
      stage I.

PMID- 11317534
TI  - [Conservative therapy of I and II stage breast cancer--successful alternative to
      modified radical mastectomy].
AB  - A clinical trial was conducted at the Center's Clinic to compare breast
      conserving treatment (quandrantectomy + radiation) (BCT) with modified radical
      mastectomy (M). It included 190 patients with stage I-II carcinoma up to 30 mm
      (BCT with "negative margin"--122; M--68). All the patients had undergone full
      axillary dissection. Mean total dose of 48.8 Gy was delivered to the whole breast
      by means of an external beam. No boost to tumor bed was given. Forty-one percent
      of tumors in the mastectomy group were of medial or central localization. The
      locoregional recurrence rates were significantly different (BCT--4.09 vs. M-
      20.5%; p < 0.001). However, the differences between distant metastasis occurrence
      and 5-year survival were not (BCT--4.91 and 95.6%; M--11.76 and 91.8%; p > 0.5,
      respectively). Nor were they significant for the localization/5-year survival
      relationship: lateral breast tumor--92%, medial--100% and central--89% (p > 0.6).

PMID- 11317535
TI  - [Malignant central nervous system tumors are susceptible to specific antibodies].
AB  - The binding of circulating specific IgG to glioblastoma cells from brain tumor
      biopsies was shown using fluorescence conjugate Protein A-FITC and Western
      blotting. Blood-brain barrier permeability for antitumor antibodies in vivo in
      glioblastoma patients is suggested.

PMID- 11317536
TI  - [Effect of live tularemia vaccine on the counter-suppression of lymphocytes and
      the end results of the combined treatment of endometrial cancer].
AB  - Starting from stage I-II, patients with endometrial tumors (ET) revealed a
      significant decline (p < 0.05) in counter-suppression lymphocytes as compared to
      healthy subjects of the same age. The correlation was particularly marked in
      cases of stage III-IV tumors (p < 0.01).

PMID- 11317537
TI  - [Low-dose cytosine-arabinoside (Ara-C) therapy for chronic myeloid leukemia].
AB  - The effects of low doses of cytosine-arabinoside (Ara-C) were studied in 17
      patients with chronic myeloid leukemia: chronic, resistant to IFN and hydroxyurea
      therapy (including 4 cases of advanced chronic disease)--7, and tumor progression
      -10. Hematologic effect was recorded in 7 chronic patients tolerant to
      hydroxyurea and alpha-interferon therapy. Among 10 cases of tumor progression,
      chronic stage II was observed in 3, stabilization (tumor progression short of
      blastic crisis)--5, and without effect--1. Low-dose Ara-C treatment was
      considered effective in 15 (88%) out of 17 patients.

PMID- 11317538
TI  - [The in-vitro effect of constant and pulsating magnetic field on immunocompetent
      blood cells of hematologic patients].
AB  - Immunologic characteristics were studied in 103 patients with multiple myeloma,
      acute leukemia, chronic lymphocytic leukemia and non-Hodgkin's disease following
      in vitro exposure of blood to a low-intensity static field (SF) and alternating
      field (AF) or pulsating magnetic field (PF). In a SF-AF study of multiple
      myeloma, a 30 min exposure had a positive effect on expression of tumor cells and
      T-cell markers and stimulated the regulatory function of T-lymphocytes. With SF
      AF and PF application alternating, the expression of both +CD3 and +CD4 and the
      +CD3/+CD4 ratio increased suggesting the lowering of immunological deficiency. In
      acute leukemia, a combined application of the magnetic fields had an effect on
      the helper activity of the T-lymphocyte subpopulation. The phagocytic activity of
      leukocytes increased significantly while their digestive ability rose to a
      moderate degree.

PMID- 11317539
TI  - [Heterogenous reaction of cancer cells to cisplatin].
AB  - During a study involving treatment of MCF-7 culture of mammary tumor cells with
      cisplatin 5.10, 15.20 and 25 microM, an inverse correlation was found between the
      first two doses and the number of dead cells; later on, this fraction diminished
      gradually to basal level. Conversely, the fraction of necrotized cells increased
      in proportion to dosage, overall toxicity of cisplatin (the sum total of dead
      cells) remaining unchanged when in excess of 10 microM.

PMID- 11317540
TI  - [Morphologic study of renal carcinogenesis in rats induced by
      dimethylnitrosamine].
AB  - 109 five-month-old albino non-inbred male rats received a single i.p. injection
      of dimethylnitrosamine (20 mg/kg b.w.) for selective induction of renal
      epithelial tumors. Forty controls were injected isotonic solution. The animals
      were autopsied 3-12 months later. Renal cell adenomas were found in 5 rats,
      mesenchymal renal--6. Renal tumor incidence increased during the experiment
      reaching 38.5% at month 12. No tumors were detected in controls. To summarize,
      our experiment failed to induce renal cell tumors only.

PMID- 11317541
TI  - [PCR-technology in the diagnosis, prognosis and therapy of oncologic disease].

PMID- 11317542
TI  - [The effect of low-energy laser radiation and interferon to delay chemical
      carcinogenesis].
AB  - A significant delay in benz(A)pyrene-induced tumorigenesis was obtained following
      three series of parenteral injection of xenogenic leukocytic interferon
      alternating with irradiation at 3-4 day intervals. Radiation was delivered from a
      red low-energy laser through a puncture in the peritoneal wall of the spleen.
      When each of said procedures was performed separately similar effects were
      recorded but the changes were not significant.

PMID- 11317543
TI  - [Combined therapy of experimental tumors with the vaccinal strain of Venezulean
      encephalomyelitis virus].
AB  - The potential of therapy with vaccinal strain of Venezuelan encephalomyelitis
      virus (VEL) in conjunction with cytostatics (cyclophosphamide) or
      immunomodulators (T-activin) has been studied. It was found that VEL in
      conjunction with cyclophosphamide inhibited the antitumor action of the drugs
      while T-activin potentiated the same effects of the virus and its oncolysate.

PMID- 11317544
TI  - [Experimental chemotherapy of malignant tumors in combination with short-term
      general hypoxia].
AB  - The effect of hypoxy on chemotherapy with emoxyl, 5-fluorouracil and bleomycin
      which are characterized by different affinities with oxygen has been
      investigated. In an experiment using 96 rats, each weighing 180 g, subcutaneously
      inoculated with Walker's carcinosarcoma and carcinoma. PC-1, combined use of
      chemotherapy and hypoxy was followed by a significant inhibition of tumor growth
      rate, against a background of significant drop in survival due to the increased
      toxic effect of the drugs. Therefore, hypoxy cannot be recommended for modifying
      chemotherapy of tumors irrespective of drug affinity with oxygen.

PMID- 11317545
TI  - [Role of macrophages in the antitumor action of the recombinant probiotic
      Subalin].
AB  - Course administration of the recombinant probiotic subalin was shown to
      significantly potentiate the cytotoxic action of macrophages from healthy and
      tumor-bearing mice against mastocytoma P-815 cells and syngeneic target cells of
      lung sarcoma of Lewis. Carrageenan, an inhibitor of macrophage activity,
      significantly cut down the antimetastaic effect of subalin. The crucial role of
      macrophages in the mechanism of this function of the drug is discussed.

PMID- 11317546
TI  - [Specifics of diagnosis in primary-multiple synchronous tumors of the head and
      neck].
AB  - The data of 100 case histories of primary-multiple synchronous malignancies of
      the head and neck have been analyzed. A second tumor was not detected during
      examination of the first one in every third case. The presence of tumor and pain
      were reported mostly by patients with neoplasms of the tongue, oral mucosa and,
      less frequently, laryngopharynx. In more than half the cases (48%), head and neck
      tumors were detected by physical examination. The most frequent were laryngeal
      tumors (30%), followed by those of the thyroid gland (26%). Second tumor
      incidence in the lung was (31%), breast (19%) and gastrointestinal tract (18%).

PMID- 11317548
TI  - [Diagnosis and choice of therapy in primary and metastatic ovarian tumors].

PMID- 11317547
TI  - [Combination therapy of lung cancer with metastatic pleurisy].
AB  - The data on the surgical and combined treatment of 35 cases of lung cancer
      associated with pleural effusion detected during surgery have been evaluated.
      Mean 5-year survival was 68.5%, pleural effusion--70%.

PMID- 11317549
TI  - [Radiodiagnosis of minimal breast cancer].

PMID- 11317550
TI  - Reclassifying cancer, guided by genomics.

PMID- 11317551
TI  - Poc testing. Beefed-up QC gives rise to ruckus.

PMID- 11317552
TI  - Winona, Web forge healthy connection.

PMID- 11317553
TI  - How our efforts add up.

PMID- 11317554
TI  - Roughing out D-dimer's role.

PMID- 11317555
TI  - A look at new assays.

PMID- 11317556
TI  - Congress passes Pap test, TC payment measures.

PMID- 11317557
TI  - Information please--SNOMED answers call.

PMID- 11317558
TI  - POC communication.

PMID- 11317559
TI  - Survey says: labs shy on leukoreduction QC.

PMID- 11317560
TI  - HER2 testing.

PMID- 11317561
TI  - Sperm counting QC.

PMID- 11317562
TI  - Clutter-free POC testing nearing reality.

PMID- 11317563
TI  - Fact vs. folklore: dealing with CJD.

PMID- 11317564
TI  - Everyday DNA--extraction gets easier.

PMID- 11317566
TI  - Arraying the data.

PMID- 11317565
TI  - For labs, HIPAA a hassle but no horror.

PMID- 11317567
TI  - Waiving co-payments and deductibles for indigent patients.

PMID- 11317568
TI  - Getting the most from your phone system.

PMID- 11317569
TI  - The meeting you won't want to miss: annual strategic planning.

PMID- 11317570
TI  - 14 alternative practice styles.

PMID- 11317571
TI  - Implementing preventive care flow sheets.

PMID- 11317573
TI  - Needlestick prevention bill will impact physician offices.

PMID- 11317574
TI  - Trends in the consumer price index.

PMID- 11317575
TI  - Solving the problem of the uninsured.
AB  - During the past 12 years, the number of uninsured has continued to climb. A sign
      of hope occurred in 1999, however; a decline of 1.7 million people was
      registered. While this decrease brings optimism of a new downward trend replacing
      the old upward trend, the number of uninsured remains unacceptably high-42.6
      million people. Additionally, a significant portion of the 1.7 million people who
      were able to obtain health insurance were individuals covered by employment-based
      insurance, leading one to believe that the decline in the uninsured that we saw
      in 1999 might be connected to the US economy's full employment status. Supporting
      this thought is the Census Bureau's finding that the 10.4 million poor who had no
      health insurance in 1998 did not change significantly in 1999. This article
      provides a profile of the uninsured and describes how health care's evolution
      towards a market place commodity has contributed to America's unacceptably high
      number of uninsured. After reviewing various programs and initiatives launched in
      an attempt to expand health care coverage, a summary of problems with the current
      program is provided. An alternative is offered.

PMID- 11317576
TI  - Getting the most out of the clinical encounter: the four habits model.
AB  - Medical interviewing is the foundation of medical care and is the clinician's
      most important activity. A growing body of evidence suggests that clinicians use
      distinctive, describable behaviors to conduct medical interviews. This article
      describes four patterns of behavior that we term Habits and reviews the research
      evidence that links each Habit with both biomedical and functional outcomes of
      care. The Four Habits are: Invest in the Beginning, Elicit the Patient's
      Perspective, Demonstrate Empathy, and Invest in the End. Each Habit refers to a
      family of skills. In addition, the Habits bear a sequential relationship to one
      another and are thus interdependent. The Four Habits approach offers an efficient
      and practical framework for organizing the flow of medical visits. It is unique
      because it concentrates on families of interviewing skills and on their inter
      relationships.

PMID- 11317577
TI  - Protect your practice's cash flow: controls in the charge generation cycle.

PMID- 11317578
TI  - Organizing for effective managed care contracting.
AB  - While many forums have debated the fairness and ethical implications of managed
      care arrangements, it is unlikely that physicians will escape practicing within
      fixed budgets in the future; the economics of health care simply requires it.
      Although a backlash has developed against managed care, it is actually more
      recognition of how pervasive it has become, rather than any threat to its
      existence. Currently managed care comprises the majority of commercial insurance,
      is making substantial inroads into Medicaid, and is challenging the reductions in
      Medicare reimbursement by dropping plans at a time when the Federal government's
      entire strategy for controlling Medicare costs is based upon managed care through
      its Medicare+Choice program.

PMID- 11317579
TI  - Reducing and managing overtime.
AB  - Overtime is undesirable for many reasons. It can deteriorate staff morale,
      reinforce and reward inefficiency, and reach deep into your practice's pockets,
      often without improving your bottom line. Many employers overuse overtime and
      hold many misconceptions about their legal obligations. This article explores
      specific practice management methods for reducing or eliminating the need for
      overtime. It dispels three popular misconceptions about employers' legal
      obligations when paying overtime. Finally, it summarizes the basic rules for
      paying overtime, including how to calculate an employee's regular rate of pay,
      how to structure a legitimate workweek, and when and how overtime payments should
      be made.

PMID- 11317580
TI  - Premises liability.
AB  - Premises liability is an often-overlooked legal consideration. Financially
      destructive cases brought against practices by patients or visitors can be
      avoided by creating a safe work environment and clearly labeling potentially
      harmful locales in and around the office in which you work. This article
      discusses clear ways any physician or office manager can avoid major legal
      problems by paying close attention to the needs and rights of office invitees.
      The focus of any physician considering insurance should include not only
      malpractice insurance but also premises liability insurance.

PMID- 11317581
TI  - Reducing physician vulnerability to professional liability claims: what practices
      make a difference?
AB  - Physicians--both "good" and "bad"--may find themselves targeted in medical
      malpractice lawsuits for reasons not necessarily related to recognized acts of
      commission or omission. As a result, taking appropriate steps to reduce their
      vulnerability to claims that may eventually be brought against them makes good
      sense from a risk management perspective. This article looks at the frequency,
      severity, reasons for, and "misadventures" associated with one physician-owned
      medical malpractice company's professional liability claims and offers selected
      practice management strategies that can help enhance physicians' defensibility in
      the event they are sued.

PMID- 11317583
TI  - Voice recognition in clinical medicine: process versus technology.
AB  - Large-vocabulary, continuous voice recognition technology, as well as the voice
      recognition industry, have matured to the point that the available tools are
      affordable and powerful enough to provide clinicians with an alternative to
      keyboard data entry. However, use of voice recognition technology in clinical
      medicine faces several practical process-oriented hurdles that may restrict the
      use of this technology to certain types of activities. For example, the use of
      voice recognition technology for dictation raises practical issues of privacy,
      security, and confidentiality. However, the same economic pressures that forced
      many clinicians to learn the keyboard instead of relying on a secretary may push
      clinicians from the keyboard to the microphone.

PMID- 11317582
TI  - Voluntary disclosure by health care providers: should you do it?
AB  - This article addresses the factors a provider needs to consider when evaluating
      whether to voluntarily disclose billing errors or billing fraud. It outlines
      procedures for the Office of the Inspector General's formal voluntary disclosure
      program as well as mechanisms for correcting routine billing errors with a
      carrier.

PMID- 11317584
TI  - Death and taxes are more than just a certainty.
AB  - This article discusses a tax provision referenced under Internal Revenue Code
      Section 691(a) known as "Income in Respect of a Decedent" (IRD) and includes many
      circumstances applicable to physicians. "IRD" refers to income that accrued to
      the decedent but was not included in taxable income.

PMID- 11317585
TI  - Urban malaria transmission in Mutare City; an unlikely phenomenon.
AB  - OBJECTIVE: With an average altitude of 1,113 m above sea level and a mean maximum
      temperature of 28.6 degrees C, malaria transmission is possible in Mutare.
      Against transmission is the regular occurrence of ground frost. We reviewed
      epidemiological data and undertook a survey for the Anopheles vector. DESIGN: The
      Anopheles survey used standard techniques for sampling larvae and adult
      mosquitoes. Species identification was done by the polymerase chain reaction
      (PCR) technique. A random sample of blood slides was examined at the Blair
      Laboratory. Patient residence was determined from the outpatient register. Daily
      maximum and minimum temperatures monitored from the Mutare Fire Station, were
      obtained from the Meteorology Office in Harare. SETTING: Mutare city and suburbs.
      RESULTS: There was no evidence of rising temperatures in Mutare. Only non-vector
      Anopheles mosquitoes were identified (An. quadriannulatus and An. pretoriensis).
      One slide positive case had gametocytes present. Mapping generally showed no
      clustering, but there were two possible transmission foci. CONCLUSION:
      Temperatures are high enough, but winter lows (< 18 degrees C) do not support
      malaria transmission in Mutare. The Anopheles survey did not find the vector. Two
      suggestive clusters were mapped. While present data do not support ongoing
      malaria transmission within Mutare, in the past, An. gambiae, An. fenestus and
      An. pretoriensis were recorded. Careful monitoring will be needed.

PMID- 11317586
TI  - Narrative themes in responses to trauma in a religious community.
AB  - OBJECTIVE: The development of a meaningful narrative of trauma experiences is an
      important factor in recovery, and religious beliefs may constitute an important
      meaning system for trauma survivors. The study examined the narrative themes
      which emerged from interviews with survivors of the massacre of a church
      congregation in South Africa (N = 19). DESIGN: A descriptive, retrospective
      study. SETTING: Community based study. SUBJECTS: A volunteer sample of 19
      participants. OUTCOME MEASURES: An open ended interview and the Structured
      Clinical Interview for DSM-IV (SCID). RESULTS: Thematic analysis revealed that
      religious beliefs and practices were frequently utilised to construct a
      meaningful retrospective narrative of the massacre. The implications of the
      findings for future research with trauma survivors are discussed. CONCLUSIONS:
      Religion may provide a framework by which survivors of trauma construct a
      meaningful account of their experience, and may be a useful focus for
      intervention with trauma survivors.

PMID- 11317587
TI  - A study of the position of the mandibular foramen in adult black Zimbabwean
      mandibles.
AB  - OBJECTIVES: To determine the position of the mandibular foramen on dry adult
      mandibles and hence provide valuable information for dental and other health
      practitioners for successful inferior alveolar nerve anaesthesia. DESIGN: A cross
      sectional study. SETTING: Department of Anatomy, Faculty of Medicine, University
      of Zimbabwe, Mount Pleasant, Harare, Zimbabwe. SUBJECTS: 38 dry mandibles from
      adult black Zimbabweans. MAIN OUTCOME MEASURES: The anterior and posterior rameal
      widths, upper and lower rameal heights and the height of the lingula were
      measured with respect to the position of the mandibular foramen. The distribution
      of the foramen in relation to the occlusal plane was determined. RESULTS: The
      results showed that the position of the mandibular foramen was highly
      individualistic but on average lies at about 2.56 mm (right) and 2.08 mm (left)
      behind the midpoint of rameal width and at approximately 3 mm superior to the
      midpoint of rameal height on both sides. The mean anterior and posterior rameal
      widths were respectively 18.95 +/- 0.41 and 14.30 +/- 0.35 while the mean rameal
      heights were respectively 22.50 +/- 0.50 (upper) and 28.44 +/- 0.65 (lower). The
      distribution of the foramen in relation to the occlusal plane was 47.1% at the
      same level with the occlusal plane, 29.4% above, and 23.5% below the plane. There
      was no side variation in the position of the foramen in relation to the occlusal
      plane, in the dimensions of the ramus and in the size of the mandibular foramen
      but individual variations exist. The height of the lingula however showed great
      variation. The mean height was 8.40 +/- 0.39 (right) and 8.36 +/- 0.38 (left).
      CONCLUSION: The study has shown similarities and differences between the rameal
      dimensions and the position of the mandibular foramen in adult black Zimbabwean
      mandibles and those of other subpopulations. The clinical significance of
      accurately locating the mandibular foramen during a local anesthetic block of the
      inferior alveolar nerve is discussed.

PMID- 11317588
TI  - The efficacy and residual life span of two alphacypermethrin insecticide
      formulations (Fendona 6% suspension concentrate and Fendona Dry 15%) treated on
      mosquito bed nets.
AB  - OBJECTIVE: To compare the effects of mosquito nets treated with two formulations
      of alpha-cypermethrin insecticide with a view to recommending the most
      appropriate formulation for use to treat mosquito nets. DESIGN: Assessment of
      insecticide potency under conditions of ordinary use. SETTING: Chilonga rural
      irrigation community in south east Lowveld Zimbabwe, a holoendemic area of year
      round malaria transmission. SUBJECTS: Convenience sample of 20 household heads
      (volunteers) was issued with treated mosquito nets. INTERVENTION: Following
      mosquito net treatment and distribution, bioassay tests were carried out monthly
      for a period of six months on insecticide and placebo treated nets.
      Questionnaires were administered once, one month post treatment of nets. MAIN
      OUTCOME MEASURES: Median mosquito knock down times of mosquitoes exposed to
      insecticide treated nets and community attitude towards the use of insecticide
      treated nets. RESULTS: Average time taken to knock down the median mosquito
      progressed from 2.3 minutes to 13.0 minutes for Fendona Dry 15% and from 4.1
      minutes to 7.8 minutes for Fendona 6% SC over the six month period. The average
      time taken to knock down the median mosquito three months post-washing were 13.0
      minutes and 7.4 minutes for Fendona Dry 15% and Fendona 6% SC respectively as
      against more than 30 minutes in controls. Both insecticides exhibited some wash
      resistance properties. The side effects reported were sneezing, itching, skin
      rash and smelling. Questionnaire data suggested that alphacypermethrin treated
      mosquito nets were welcomed. CONCLUSIONS: Both insecticide formulations proved to
      be suitable candidates. This was because of their insecticidal potency, wash
      resistance properties and acceptance by the community.

PMID- 11317589
TI  - An update on human bartonelloses.
AB  - The data available on Bartonella species has increased rapidly in the last decade
      with 12 new species and subspecies being described and bartonellas being found to
      be associated with an increasing spectrum of clinical syndromes in
      immunocompetent and immunocompromised patients. In addition B. weissii is found
      in cats. This rapid expansion of knowledge has come about with the development of
      new culture and molecular biology techniques to isolate and identify the
      organisms. Much of the information on the bartonellas and the emerging infectious
      diseases they cause has been derived from the USA and Europe although there is
      growing evidence that the organisms may be important pathogens in other regions
      including southern Africa. In this review we describe the bacteriology,
      epidemiology, clinical and laboratory signs, diagnosis and treatment of
      bartonella infections and the most recent data on bartonellas in southern Africa.

PMID- 11317590
TI  - The prevalence of atherosclerosis of the abdominal aorta, common iliac and lumbar
      arteries among Zimbabweans: implications for low back pain.

PMID- 11317591
TI  - Neonatal intensive care in a developing country: outcome and factors associated
      with mortality.
AB  - OBJECTIVE: To determine outcome and factors associated with mortality in a
      tertiary level neonatal intensive care unit. DESIGN: Retrospective descriptive
      study. SETTING: Harare Central Hospital Neonatal Intensive Care Unit (NICU).
      SUBJECTS: All neonates admitted to the NICU in 1998. MAIN OUTCOME MEASURE:
      Mortality. RESULTS: A total of 234 neonates were admitted to the NICU in 1998.
      Median age at admission was one day (Q1 = 0, Q3 = 3). Median birth weight was
      1,730 gms (Q1 = 690, Q3 = 2,209). The commonest reason for admission was
      respiratory distress. Medical cases were 171 (73.1%), surgical 61 (26.1%) and two
      were not indicated. The median duration of stay in the NICU was three days (Q1 =
      1, Q3 = 6). Median age at death was three days (Q1 = 1, Q3 = 5). Case fatality
      rate was 46.4% and 85.9% died during the first week. Receiving mechanical
      ventilation was associated with high mortality. The odds of dying were 12.29
      times greater for those who were ventilated compared to those who received
      continuous positive airways pressure (CPAP) via nasal prongs. Birth weight, age
      at admission to the NICU, sex and duration of stay in the NICU had no significant
      influence on mortality. CONCLUSION: Mortality rates in this NICU were
      unacceptably high and call for urgent action. Attempts to identify true risk
      factors for the NICU mortality on the face of sub-optimal care may be misleading.
      There is need to improve neonatal audit in order to identify effective treatments
      and guide policies for the NICU care.

PMID- 11317592
TI  - Quality of life evaluation in patients with HIV-I infection: the impact of
      traditional medicine in Zimbabwe.
AB  - OBJECTIVES: To evaluate the impact of phytotherapy (traditional medicine) in
      persons with HIV infection and to assess the quality of life of those persons
      with respect to HIV disease progression, including sociodemographic
      characteristics. DESIGN: A community based open label non-intervention and
      uncontrolled cohort study. SETTING: Blair Research Institute Clinic. SUBJECTS: A
      total of 105 HIV infected persons at various stages of HIV infection. Seventy
      nine percent were on phytotherapy (PT) and 21% on conventional medical care
      (CMC). MAIN OUTCOME MEASURES: (a) Assessment of quality of life of HIV infected
      persons on phytotherapy using the WHOQol instrument, and (b) assessment of
      quality of life of those persons in relation to the HIV disease progression using
      CD4 cell counts and viral load as measure of disease progression. METHODS: We
      interviewed 105 patients with various stages of HIV-I infection in a community
      based cohort study from June 1996 to May 1998, in Harare. The 96 (91.4%)
      asymptomatic and six (8.6%) symptomatic patients underwent regular physical
      examinations and had blood drawn for laboratory tests at the baseline afterwards
      at three month intervals over a period of two years. RESULTS: The mean (s.d.) age
      was 34.9 (7.3) years; 64.4% were women and 60.3% were married. In multi variate
      analyses, age was significantly correlated with the level of independence domains
      (p = 0.032), whereas, gender was significantly correlated with social
      relationships' domains (p = 0.034). The type of treatment received was
      significantly correlated with spiritual domains (p = 0.045). Proportions of
      scores on five domains measuring different aspects of quality of life for
      patients on phytotherapy were much lower than those on conventional therapy (p <
      0.0001, for all variables). CONCLUSION: Our data support the role of phytotherapy
      in improving the quality of life of HIV-I infected patients, yet its
      pharmacological basis is unknown. The WHOQol instrument is a good measure of
      quality of life for patients with HIV infection.

PMID- 11317593
TI  - Local plants as repellents against Anopheles arabiensis, in Mpumalanga Province,
      South Africa.
AB  - OBJECTIVE: To assess the repellency effect of three local plants; fever tea
      (Lippia javanica), rose geranium (Pelargonium reniforme) and lemon grass
      (Cymbopogon excavatus) against laboratory reared Anopheles arabiensis mosquitoes.
      DESIGN: A laboratory experimental study. SETTING: Mpumalanga Province, South
      Africa. SUBJECTS: Three adult male volunteers. MAIN OUTCOME MEASURES: Affordable
      alternatives to synthetic repellents against biting of Anopheles arabiensis
      mosquitoes. RESULTS: All three alcohol plant extracts provided significantly more
      protection (p = 0.012) than alcohol control. The alcohol plant extract of L.
      javanica provided 76.7% protection against An. arabiensis after a four hour
      period, and C. excavatus and P. reniforme provided 66.7% and 63.3% protection for
      three hours, respectively. At five hours post application only L. javanica
      alcohol extract provided appreciable protection (59.3%) against An. arabiensis.
      CONCLUSION: The results of this study indicate that L. javanica, P. reniforme and
      C. excavatus protect against An. arabiensis mosquito bites with the repellent
      effect of L. javanica lasting significantly longer than that of the other two
      plants.

PMID- 11317594
TI  - Use of combining in situ hybridization and immunohistochemistry in detecting
      human papillomavirus on routine sections in cases of diagnostic uncertainty.
AB  - OBJECTIVES: To determine the combined role of in situ hybridization (ISH) and
      immunohistochemistry (IHC) in the detection of human papilloma virus (HPV)
      infection in cases of diagnostic uncertainty. DESIGN: A retrospective study.
      SETTINGS: Department of Histopathology at the University of Zimbabwe and
      Department of Pathology at the University of Texas Medical Branch at Galveston in
      Texas, both teaching referral hospitals. SUBJECTS: 23 patients with a diagnosis
      suggestive but not diagnostic of HPV infection on routine histology sections of
      uterine cervical biopsies, in which 20 had enough material to complete the study.
      MAIN OUTCOME MEASURES: Surgical pathology records of cases with morphologic
      features suggestive but not diagnostic of HPV cases were identified.
      Representative sections of each case were investigated with ISH and IHC for HPV
      infection. RESULTS: HPV DNA was detected in 12 cases. The bovine papilloma virus
      (BPV) antibody immunoreacted with six of the cases and two of these had not been
      detected by ISH resulting in a combined ISH and IHC, HPV detection of 14 cases.
      CONCLUSION: This preliminary data seems to support the validity of combining IHC
      and ISH, even though IHC is less sensitive compared to ISH, it may detect certain
      HPV types not represented in the DNA probe.

PMID- 11317595
TI  - Investigation of ascites--are we doing enough?
AB  - A case of ascites with peritonitis is described. Delayed diagnosis might have
      contributed to the death of our patient. The current tools used in investigating
      ascites with peritonitis and a review of the existing guidelines for a workup of
      these patients are discussed. The use of the laparoscopic technique is
      recommended.

PMID- 11317596
TI  - Pharmacological management of benign prostatic hyperplasia.
AB  - In men with mild to moderate BPH, pharmacotherapy is a safe and effective
      alternative to surgery. The primary care physician should be able to manage the
      treatment without referral to a urologist, provided he has undertaken appropriate
      steps to assure himself, and the patient, that there is no evidence of cancer of
      the prostate.

PMID- 11317597
TI  - Rational drug use. Part I: The role of national drug policies.

PMID- 11317598
TI  - Ineffectiveness of essential oils from Artemisia afra (Asteraceae), Lantana
      angiolensis (Verbenaceae) and Syzygium hiullense (Myrtaceae) in inhibiting
      mosquito biting.

PMID- 11317599
TI  - A comparison of unmet needs for dental and medical care among persons with HIV
      infection receiving care in the United States.
AB  - OBJECTIVE: Oral health conditions associated with HIV disease are frequently more
      severe than those of the general population, making access to both dental and
      medical care important. Using the domains specified in the Behavioral Model of
      Health Services Use, this paper examines the correlates of unmet needs for dental
      and medical care in a nationally representative sample of patients with HIV.
      METHODS: This investigation is a cross-sectional study using baseline data from
      the HIV Cost and Services Utilization Study (HCSUS), the first nationally
      representative study of persons in care for HIV. Using probability-based
      techniques, 4,042 people were randomly selected in January 1996, and 2,864 (71%)
      completed a structured interview that included questions on unmet needs for
      dental and medical care. Regression analysis was used to identify variables
      associated with having unmet needs for dental care only, medical care only, and
      both medical and dental care. RESULTS: Of the estimated 230,900 people in
      treatment for HIV in the United States, approximately 58,000 had unmet medical or
      dental needs based on self-reported data. Unmet dental needs were more than twice
      as prevalent as unmet medical needs (32,900 vs 14,300), and 11,600 people were
      estimated to have both types of unmet needs. Multinomial logit regression showed
      that persons with low income had increased odds of reporting unmet needs for both
      dental and medical care. The uninsured and those insured by Medicaid without
      dental benefits had more than three times the odds of having unmet needs for both
      types of care than did the privately insured. CONCLUSIONS: To serve both the
      dental and medical needs of diverse populations affected by HIV disease, greater
      coordination of services is needed. In addition, state insurance programs for
      people with HIV should consider the feasibility of expanding their benefit
      structure to include dental care benefits.

PMID- 11317600
TI  - A cluster randomized controlled trial of a dental health education program for 10
      year-old children.
AB  - OBJECTIVE: Using a cluster randomized trial, this study tested the effectiveness
      of a dental health education program designed to improve the oral hygiene and
      dental knowledge of 10-year-old children. METHODS: Thirty-two primary schools in
      the northwest of England participated. After a baseline assessment of plaque and
      the completion of a dental knowledge questionnaire by the children, the schools
      were allocated randomly to active or control groups. Children in schools
      allocated to the active group received the dental health program, which consisted
      of four one-hour lessons. After four months the children were examined clinically
      and scored for plaque, and a second questionnaire was administered. The schools
      in the control group were then allocated randomly to receive the program or not
      over the following three months, the program being withdrawn from the schools who
      initially received it. A further assessment of plaque was made and a
      questionnaire administered seven months after the baseline of the study. RESULTS:
      The active groups had 20 percent and 17 percent lower mean plaque scores than the
      control group at four and seven months (P < .001). The children's knowledge of
      which type of toothbrush should be used and the role of disclosing tablets
      improved in the initial test group when compared with the control group and this
      was retained over the second part of the study. CONCLUSION: The children
      receiving the program had significantly lower mean plaque scores and greater
      knowledge about toothbrushes and disclosing tablets than the control children who
      had not received the program.

PMID- 11317602
TI  - On common ground. Keynote address at the joint annual meeting of the American
      Association of Public Health Dentistry and the Association of State and
      Territorial Dental Directors.

PMID- 11317601
TI  - Successful implementation of community water fluoridation via the community
      diagnosis process.
AB  - OBJECTIVES: This paper describes the community diagnosis process and how it was
      used to implement community water fluoridation in Tennessee. METHODS: Public
      health dental staff developed a survey instrument to collect community-specific
      data on the oral health status of schoolchildren. Key survey findings were
      presented to county health councils who were determining and prioritizing the
      health needs of their communities. RESULTS: Community-specific data showed higher
      caries levels in children without access to an optimally fluoridated community
      water supply. Presentation of local survey findings to county health councils
      resulted in fluoridation being a high-priority health issue in several counties.
      With health council support, opposition to fluoridation by utility district
      officials was overcome when decision makers were challenged with local survey
      findings. The community diagnosis process resulted in the successful fluoridation
      of six community water systems serving a total of 33,000 residents. CONCLUSIONS:
      The community diagnosis approach was successful in implementing community water
      fluoridation in geographic areas historically opposed to this public health
      measure. The success of these fluoridation initiatives was attributed to: (1)
      current, community-specific assessments of children's oral health; (2)
      identification of communities with disparate oral health needs, problems, and
      resources; and (3) effective presentation of community-specific oral health
      survey data to community leaders, stakeholders, and decision makers.

PMID- 11317603
TI  - A community participatory oral health promotion program in an inner-city Latino
      community.
AB  - OBJECTIVES: This paper reports the planning, implementation, process evaluation,
      and refinement of an oral health community participatory project in Mount
      Pleasant, an inner-city Latino neighborhood of Washington, DC. The main goal was
      to explore the feasibility of implementing such a project. METHODS: The PRECEDE
      PROCEED model was used to guide the planning and process evaluation of this
      project, in conjunction with community organizational methods. A steering
      committee, which met periodically, was formed to assist in program planning,
      implementation, and evaluation. The needs assessment of the community identified
      extensive dental health problems among children and deficiencies in their
      parents' oral health knowledge, opinions, and practices. In response, culturally
      appropriate health education and promotion activities were planned and
      implemented in collaboration with local community organizations, volunteers, and
      local practitioners. Process evaluation was used to provide feedback into the
      refinement of the community approach, which included record keeping and an
      inventory approach to activities completed and resources used. The overall impact
      and usefulness of this program were assessed informally using an anonymous open
      ended questionnaire directed to members of the steering committee, and an
      outreach survey using a convenience sample at a local Latino health fair.
      RESULTS: The implementation of such a community participatory approach was
      feasible and useful for building upon existing local resources and addressing
      oral health concerns in a community not reached by traditional dental care and
      health promotion initiatives. Individuals in this community showed a substantial
      interest in oral health matters and participated in a variety of oral health
      prevention activities. The community approach adhered to community-based research
      principles.

PMID- 11317605
TI  - If it can't be put into words....

PMID- 11317604
TI  - Clinical factors related to noncompletion of root canal therapy.
AB  - OBJECTIVES: This study identified clinical factors related to noncompletion of
      root canal therapy (RCT) among patients in a dental health maintenance
      organization (HMO) based in Portland, OR. METHODS: A secondary analysis of a case
      control study was conducted using data from 303 individuals enrolled continuously
      in the HMO from January 1, 1987, through December 31, 1994, who received
      endodontic access on a permanent nonwisdom tooth in 1987 or 1988. Person- and
      tooth-level characteristics were evaluated to compare patients whose accessed
      tooth was obturated by December 31, 1994, with patients whose accessed tooth was
      not obturated by that date. Written and electronic records were reviewed to
      ascertain study variables, and multivariate logistic regression models were
      developed to describe differences between the two groups. RESULTS: Incomplete RCT
      was more common among patients who were symptomatic prior to access and had more
      missing first molars at access. It also was more common among teeth that were
      decayed, had more pockets > or = 5 mm, and had fewer decayed or filled surfaces
      at access. CONCLUSIONS: Because patients with greater evidence of past and
      current oral disease were less likely to have completed RCT, they may require
      additional counseling about the importance of carrying through with prescribed
      treatment.

PMID- 11317606
TI  - Assessing stress and coping in pregnancy and postpartum.
AB  - This paper evaluates questionnaire measures of stress and coping for use with
      pregnant and postpartum women. For each area of measurement the main issues or
      problems are delineated, appropriate measures are described and the validity and
      reliability of the measures are discussed, as well as the problems and benefits
      of using each measure with pregnant or postpartum women. Finally, norms are
      provided for female and obstetric samples, where available. The following
      constructs are examined: stress, demands of the infant, social support, coping
      and repressive coping style. A version of the Hassles and Uplifts Scale that was
      shortened for use with postpartum women is appended. It is hoped that this paper
      will provide a valuable resource for future research into stress and coping in
      pregnant and postpartum women.

PMID- 11317607
TI  - Sexual activity during pregnancy and after childbirth: results from the Sexual
      Preferences Questionnaire.
AB  - The sexual relations of expectant and young parents have been researched
      relatively often, but most studies are restricted to female participants, samples
      from the USA, a short postpartum period and a reductionist view of sexuality as
      equivalent to intercourse. The aim of this study is to gain more knowledge about
      sexual activity of German couples with regard to non-genital tenderness, French
      kissing, breast stimulation, manual-genital stimulation, cunnilingus, fellatio,
      vaginal intercourse, anal intercourse and masturbation during pregnancy and the
      first 6 months postpartum. As part of a larger longitudinal study, 60 women and
      men (30 couples) answered a newly developed Sexual Preferences Questionnaire
      (SPQ) which assesses sexual activity and enjoyment. The frequency of most
      heterosexual activities declined during pregnancy, reached almost zero in the
      first 3 months postpartum, and then began to increase; male masturbation remained
      relatively constant. Agreement between the two members of each couple was
      assessed and SPQ data were validated with other questionnaire data and interview
      data. The results are discussed with regard to limitations of the sample. Future
      research should broaden the range of questions investigated, the range of
      research methods applied (questionnaires and interviews) and the range of persons
      researched (both partners).

PMID- 11317608
TI  - Semmelweis and puerperal fever.

PMID- 11317609
TI  - Parents' coping in the neonatal intensive care unit: a theoretical framework.
AB  - The conceptual framework that has been widely used to study the coping strategies
      of parents of preterm infants in neonatal intensive care units (NICU) has been
      the transactional model of stress and coping proposed by Lazarus and colleagues.
      This model supports the cognitive system as the key factor in stress
      transactions. The cognitive system produces an interpretation of events that
      leads to making sense of numerous sensations and perceptions from both external
      and social sources as well as from the internal physiological environment. The
      individual cognitive system appraises stimuli in two ways: primary appraisal and
      secondary appraisal. Another factor that may influence the individual's coping
      effort is gender difference. Mothers and fathers of preterm infants have been
      found to use different coping strategies to deal with the preterm birth. Other
      factors such as personality traits and the perceived and actual availability of
      social support may also influence the parents' coping effort. Implications for
      clinical practice by the NICU interdisciplinary team are considered.

PMID- 11317610
TI  - Review of the role of progesterone in the management of postnatal mood disorders.
AB  - Postnatal mood disorders (maternity blues, postnatal depression and puerperal
      psychosis) are cross-cultural symptoms that are commonly seen in primary care by
      general practitioners and midwives, by gynecologists and obstetricians, and
      within the psychiatric services. One of several hypotheses for their causation is
      falling progesterone levels in the postpartum period. Progesterone supplements
      are therefore currently used in the treatment of postnatal mood disorders, both
      in primary and secondary health care settings. The evidence for this is reviewed.
      The MEDLINE and PSYCHLIT databases from 1966 to 1999 were searched. References
      reporting observational data on progesterone levels around delivery or
      therapeutic studies using progesterone were retrieved. Additional references were
      identified by citation tracking from these and direct contact with available
      authors. Eight papers were identified. Although there is some weak evidence for
      its role in maternity blues and some theoretical justification for its use, there
      is no robust primary research to support the use of progesterone in the treatment
      of postnatal mood disorders. Progesterone is being used to prevent recurrence of
      postnatal depression but the evidence supporting its efficacy is lacking. Its use
      in the treatment of postnatal mood disorders cannot be recommended on the basis
      of current evidence. Randomized controlled trials are needed to decide if it has
      a role in the treatment and prevention of postnatal mood disorders.

PMID- 11317611
TI  - Herzog Blaubart's Burg: forbidden territories in human reproduction.

PMID- 11317612
TI  - Response to Renckens.

PMID- 11317613
TI  - Factors associated with elective termination of pregnancy among Canadian and
      American women with nausea and vomiting of pregnancy.
AB  - Case reports have associated severe nausea and vomiting of pregnancy (NVP) with
      elective termination of pregnancy. Therefore, our objective was to explore the
      determinants of consideration of termination and actual termination of pregnancy
      among women with NVP. From 1996 to 1997, callers to an advertised NVP Healthline
      underwent a semi-structured interview. From callers who retrospectively reported
      on NVP in a previous pregnancy, a nested unmatched case-control study was
      performed. Callers were divided into three groups: those who reported having
      electively terminated their pregnancy due to NVP, those who considered
      termination due to NVP and those who never considered termination. The severity
      of nausea and vomiting, and frequency of psychosocial morbidity, were compared
      between cases and controls, and multivariate logistic regression analysis was
      used to determine factors independently associated with termination and/or
      consideration of termination of pregnancy due to NVP. Of 3201 callers with NVP,
      413 women reported having considered termination of pregnancy for NVP, 108
      reported termination due to NVP and 2609 reported never having considered
      termination for NVP. The following factors were independently associated with a
      woman's consideration of termination of pregnancy due to NVP: unplanned pregnancy
      (p = 0.002), multiparity (p = 0.0001), more severe vomiting (p = 0.003), feelings
      of depression (p < 0.0001) and reported adverse effects of NVP on both her
      partner's daily life (p = 0.04) and her relationship with her partner (p =
      0.0003). The following factors were independently associated with actual
      termination of pregnancy due to NVP: unplanned pregnancy (p < 0.0001),
      multiparity (p = 0.03) and feelings of depression (p = 0.001). There were no
      significant interactions between factors. Consideration of termination, or actual
      termination of pregnancy, due to NVP are associated with psychosocial
      circumstances, which should be taken into consideration when managing these
      women.

PMID- 11317614
TI  - Postcode prescribing and the Human Rights Act 1998.

PMID- 11317615
TI  - Training for colonoscopy.

PMID- 11317616
TI  - The changing relationship between the public and the medical profession.

PMID- 11317617
TI  - The Mozart effect.

PMID- 11317618
TI  - Dramatic parasomnias.

PMID- 11317619
TI  - Sleep problems in children with developmental disorders.

PMID- 11317620
TI  - Emergency surgery: atavistic refuge of the general surgeon?
AB  - A prospective audit of emergency soft-tissue surgery for an eight-week period
      revealed that general surgical emergency operations were more than twice as
      common as those undertaken in other soft-tissue specialties. The audit reveals
      that emergency general surgery needs an increase in resources, an increase in
      available staff and an increase in the role of the consultant general surgeon on
      call. An alternative solution would be to admit soft-tissue emergencies by
      specialty and develop specialist emergency services.

PMID- 11317621
TI  - Paradoxical outcome after use of hyaluronate barrier to prevent intra-abdominal
      adhesions.

PMID- 11317622
TI  - Computer game delusions.

PMID- 11317623
TI  - Nipple excised and areola retained after total mastectomy (NEAT).

PMID- 11317624
TI  - Superficial thrombophlebitis followed by pulmonary embolism.

PMID- 11317625
TI  - Pulmonary embolism after intravenous immunoglobulin.

PMID- 11317626
TI  - Dementia with a prosthetic aortic valve.

PMID- 11317627
TI  - Healthcare in rural China: a view from otolaryngology.

PMID- 11317628
TI  - Sir James Reid, Bt: royal apothecary.

PMID- 11317629
TI  - The history of cryosurgery.

PMID- 11317630
TI  - Leechcraft.

PMID- 11317631
TI  - Screening for lung cancer.

PMID- 11317632
TI  - Whiplash.

PMID- 11317633
TI  - Social problem-solving skills training for incarcerated offenders. A treatment
      manual.
AB  - This article describes a social problem-solving skills intervention for
      incarcerated adult offenders. The program includes pragmatic, progressive skill
      building through the use of direct instructions, role-plays with performance
      feedback, modeling, behavior rehearsal, and positive reinforcement. In addition
      to these treatment components, the empirically derived approach employs
      standardized assessment measures to identify deficits and to evaluate treatment
      outcome. Assessment data are directly used to determine behavior change in such
      areas as conversational skills, positive and negative assertion, anger
      management, problem solving, empathy, and stress inoculation. Social skills
      training is included to modify verbal, nonverbal, and paralinguistic behavioral
      components. In addition, training elements related to anger reduction and stress
      management are utilized.

PMID- 11317634
TI  - An experimental analysis of aggression.
AB  - Iwata, Dorsey, Slifer, Bauman, and Richman developed an assessment method to
      identify the operant functions of self-injurious behavior. In this study, a
      similar method was used to assess the operant functions of aggression displayed
      by children and adolescents with developmental disabilities. Although previous
      research has shown that aggression is an operant behavior, there has been no
      comprehensive analysis of aggression using analog functional analysis method.
      Eight children and adolescents participated. The experimental conditions involved
      attention, escape, materials, no interaction, and control. Results for 7 of the 8
      participants identified clear operant functions (positive or negative
      reinforcement) for aggression. For 1 child, subsequent analyses suggested that
      aggression was possibly sensitive to peer attention as reinforcement.

PMID- 11317635
TI  - Intervention in compulsive hoarding. A case study.
AB  - Historically, the compulsive hoarding of possessions has been examined in the
      context of other obsessive-compulsive disorders. More recently, researchers have
      begun to explore compulsive hoarding as a separate and distinct syndrome. The
      cognitive behavioral model proposed by Frost and Hartl suggests that deficits in
      information processing, emotional attachment problems, behavioral avoidance, and
      beliefs about the nature of possessions are important components in understanding
      compulsive hoarding. This article presents a case study of a successful
      intervention with a compulsive hoarder that addresses each of the components
      proposed in the model. Implications for future interventions are discussed.

PMID- 11317636
TI  - General case quasi-pyramidal staff training to promote generalization of teaching
      skills in supervisory and direct-care staff.
AB  - The authors employed staff training strategies designed to enhance generalization
      of teaching skills in staff working with persons with developmental disabilities.
      Staff training consultants initially employed a general case training approach
      involving the use of specially selected client program exemplars to provide three
      supervisory staff with generalized teaching skills. Subsequently, supervisory
      staff used the general case approach to train teaching skills to direct-care
      staff, with staff training support from the consultants (quasi-pyramidal
      training). Supervisors showed improvement in teaching skills after supervisory
      staff training, but only one of the three supervisors exceeded 70% correct skill
      use. After participating in the training of their own staff, however, supervisors
      demonstrated further improvements in skill use. All direct-care staff showed
      improvement after quasi-pyramidal training, with seven of the nine staff
      exceeding 70% correct skill use. General case quasi-pyramidal training appears to
      have potential as a strategy for promoting generalization of staff teaching
      skills in both trainees and trainers.

PMID- 11317637
TI  - A brief behavioral activation treatment for depression. Treatment manual.
AB  - The brief behavioral activation treatment for depression is a simple, cost
      effective method for treating depression. Based on basic behavioral theory and
      recent evidence that the behavioral component may be the active mechanism of
      change in cognitive-behavioral treatments of clinical depression, the authors
      designed a treatment to systematically increase exposure to positive activities,
      and thereby improve affect and corresponding cognitions. This article describes
      the rationale for the treatment and provides the treatment in manual form to be
      utilized by patients in therapy.

PMID- 11317638
TI  - Using antecedent manipulations to distinguish between task and social variables
      associated with problem behaviors exhibited by children of typical development.
AB  - In the antecedent functional assessment literature, researchers have introduced
      task demands and social attention simultaneously while varying the level of task
      difficulty. Though research has demonstrated situations in which a combination of
      social and task antecedents occasion socially avoidant responses from children
      with disabilities, no current studies have been offered to assess the impact of
      high levels of adult attention devoid of task demands on problem behaviors
      exhibited by children of typical development. A multiple element design was used
      to assess the specific effects of task and social antecedents on the problem
      behaviors of four children of typical development. Results identified two
      children whose behavior was associated with a combination of difficult task
      demands and attention in the form of commands and redirections and two children
      whose behavior was associated only with high levels of adult attention that did
      not include commands or redirections. These results suggest that antecedent
      functional assessment procedures can assess the impact of high levels of
      attention without the presence of task demands.

PMID- 11317639
TI  - The influence of a token economy and methylphenidate on attentive and disruptive
      behavior during sports with ADHD-diagnosed children.
AB  - Three children diagnosed with attention deficit hyperactivity disorder (ADHD)
      participated in a summer program designed to evaluate the influence of stimulant
      medication and a token economy on attentive and disruptive behavior during
      kickball games. Attentive and disruptive behavior were assessed using an interval
      coding system, and daily ratings on the ADHD Index of the Conners Teacher Rating
      Scale-Revised were also obtained. A multielement reversal design was used, and
      the results indicated that both interventions independently improved attentive
      behavior and decreased disruptive behavior for the participants. Contrary to
      other research, when the token economy and medication were compared in isolation,
      the token system appeared more effective in reducing disruptive behavior for 2 of
      the 3 participants. In addition, the token system generally enhanced the effects
      of stimulant medication.

PMID- 11317640
TI  - Recent progress in clinical and basic pertussis research.
AB  - Over the last decade, substantial progress has been made in the field of
      pertussis research. This includes better understanding of virulence mechanisms
      and their influence on the pathogenicity of Bordetella pertussis, increased
      awareness of the broad spectrum of disease and more insight into the host's
      immune response to infection, improved diagnostic tools, development, evaluation,
      introduction and implementation of several acellular pertussis vaccines and
      better understanding of the epidemiology of pertussis in adolescents and adults.
      CONCLUSION: The major achievements in the field of pertussis research are
      reviewed and discussed. They have great impact on the current and future practice
      of paediatric, adolescent and adult medicine.

PMID- 11317641
TI  - Decision making in extreme situations involving children: withholding or
      withdrawal of life supporting treatment in paediatric care. Statement of the
      ethics working group of the Confederation of the European Specialists of
      Paediatrics (CESP).

PMID- 11317642
TI  - Endogenous nitric oxide and endothelin-1 in persistent pulmonary hypertension of
      the newborn.
AB  - We studied changes in endogenous nitric oxide (NO) synthesis and endothelin-1 (ET
      1) production in infants with persistent pulmonary hypertension of the newborn
      (PPHN). We determined concentrations of serum NO metabolites, i.e., nitrites and
      nitrates (NOx), and of plasma ET-1 in five infants with PPHN (PPHN group) and in
      25 healthy full-term neonates (control group). In both groups, serum NOx
      concentrations increased over time and plasma ET-1 concentrations decreased with
      age. The differences in serum NOx concentrations between groups were not
      significant at < 12 h and 24 h of age; however, they were significantly higher in
      the PPHN group than in the control group at 5 days of age. The differences in
      plasma ET-1 concentrations between groups were not significant at 5 days of age,
      but were significantly higher in the PPHN group than in the control group at < 12
      h and 24 h of age. CONCLUSION: Limited endogenous nitric oxide synthesis and
      elevated endogenous endothelin-1 production during the first few days of life may
      contribute to pulmonary hypertension in infants with persistent pulmonary
      hypertension of the newborn.

PMID- 11317643
TI  - Clinical and histopathological findings in two Turkish children with follicular
      bronchiolitis.
AB  - We report on two Turkish children who presented with progressive airway
      obstruction. Open lung biopsy revealed follicular bronchiolitis. The children
      were treated with systemic steroids and various topical medications. Whereas the
      respiratory situation of patient 1 required immunosuppressive therapy, the
      condition of patient 2 stabilised without systemic medication. CONCLUSION:
      Diagnosis of follicular bronchiolitis should be considered when children present
      with recurrent respiratory tract infections, progressive dyspnoea, and chronic
      bronchial obstruction. Children in whom follicular bronchiolitis is suspected
      should undergo open lung biopsy for confirmation of diagnosis.

PMID- 11317644
TI  - Left ventricle dimensions in preterm infants during the first month of life.
AB  - This study was designed to evaluate left ventricle dimensions in preterm infants
      during the first month of life, in order to define reference values and their
      correlation with gestational age, birth weight, gender and baseline. Thirty-five
      infants, gestational age 25-29 (mean 27.9 +/- 1.4) weeks, birth weight 750-1249
      (mean 965 +/- 206) g, were measured using echocardiography on days 3, 7, 14, 21
      and 28 of life. The following dimensions were measured: end-systolic and end
      diastolic interventricular septum thickness, end-systolic and end-diastolic left
      ventricle posterior wall thickness, end-diastolic and end-systolic left ventricle
      diameter. A progressive and significant increase of all the left ventricle
      measurements was observed during the first month of life. Left ventricle
      dimensions at the first scan (Day 3) correlated with birth weight but not with
      gestational age and gender. The degree of the increase observed during the first
      month of life was inversely related to the baseline, suggesting that the smaller
      the left ventricle is at birth, the higher is its postnatal increase toward
      dimensions similar to those of term infants. Our study gives reference data about
      left ventricle dimensions of preterm infants during the first month of life and
      is helpful when making a diagnosis of left ventricular hypertrophy in these
      subjects.

PMID- 11317645
TI  - Delayed recognition of haemodynamically relevant congenital heart disease.
AB  - Delayed recognition of congenital heart defects may have a serious impact on the
      long-term outcome of the children affected. It was the aim of the present study,
      to evaluate the proportion of children with delayed cardiac diagnosis out of a
      large cohort of consecutive paediatric patients requiring treatment for
      congenital heart disease. A prospective study was performed over a 3-year period.
      Of all 323 paediatric patients requiring surgical (n = 291) or catheter
      interventional (n = 32) treatment for congenital heart disease, patients with
      delayed diagnosis of their cardiac defects were observed and especially examined
      for the presence of clinical cardiac findings other than systolic murmurs, not
      recognized as such prior to referral. Of all the patients, 32 (10%) had delayed
      diagnosis of heart defects. Surprisingly, the proportion of late diagnoses was
      not different in the group of patients with cyanotic heart disease where 7/72
      patients were referred with delay, compared to 25 delayed referrals among 251
      children with acyanotic heart defects. Of the 32 patients with delayed diagnosis,
      7 had complications due to delayed referral, but there was no mortality
      associated with late diagnosis. CONCLUSION: A substantial proportion of all
      paediatric patients requiring intervention for heart disease were diagnosed with
      relevant delay. In all study patients with late diagnosis, clinical cardiac
      findings other than systolic murmurs were present that should have alerted the
      physician on the possible presence of underlying heart disease.

PMID- 11317647
TI  - Primary B-cell lymphoma of bone in children.
AB  - Primary lymphoma of bone (PLB) is a rare entity of extranodal non-Hodgkin
      lymphoma (NHL). We report on two children with PLB focussing on diagnostic
      evaluation and treatment strategy. Clinical and radiographic presentation in both
      children suggested a primary bone tumour such as Ewing sarcoma. A 13-year-old
      girl showed osteolytic tumours in the right 7th rib and right iliac crest.
      Additional skeletal lesions were found by whole-body positron emission
      tomography. A 6-year-old boy presented with an isolated, osteolytic lesion of the
      left distal femur. In both patients staging procedures excluded any organ
      involvement besides the skeletal tumours. Tumour biopsy and immunohistological
      studies revealed lymphoblastic non-Hodgkin lymphoma of B-cell lineage in both
      children. They received a polychemotherapy for B-cell lymphoma according to the
      NHL-BFM 95 protocol and are in complete remission with a follow up of 24 and 18
      months respectively. CONCLUSION: Isolated, primary lymphoma of bone in children
      may clinically and radiographically impose as primary bone tumour. Multiple
      therapeutic strategies have been applied in the treatment of this malignancy,
      however, treatment modalities are not well focussed on immunological patterns in
      the case of primary lymphoma of bone. Staging techniques should include
      immunophenotyping to initiate specific cell lineage treatment.

PMID- 11317646
TI  - Rhinocerebral zygomycosis in childhood acute lymphoblastic leukaemia.
AB  - The hazards associated with invasive candidiasis and aspergillosis in oncology
      patients are well recognised. These conditions typically present late in
      treatment, often after prolonged or recurrent episodes of neutropenia. We report
      the occurrence of Absidia corymbifera infection causing rhinocerebral zygomycosis
      in two children with acute lymphoblastic leukaemia, early in the induction phase
      of treatment and within a 3-month interval, in the same oncology unit. The
      initial presentation of facial pain was rapidly followed by the development of
      cranial nerve palsies, cavernous sinus thrombosis, diabetes insipidus, seizures
      and death within 9 days of symptom onset, despite aggressive management with high
      dose liposomal amphotericin (Ambisome), surgical debridement and local
      instillation of amphotericin solution. These cases highlight the need for
      awareness of zygomycosis as a potentially lethal fungal infection that can
      present even with short duration exposure to the usual risk factors. Their
      occurrence within a limited time period raises questions as to the relative
      importance of environmental exposure. The failure of medical and surgical
      intervention to impact on the course illustrates the need to develop appropriate
      preventative strategies which may have to incorporate measures to reduce the
      environmental exposure of susceptible patients.

PMID- 11317648
TI  - Bleeding tendency in Wolfram syndrome: a newly identified feature with phenotype
      genotype correlation.
AB  - Wolfram syndrome (WS) is a recessively inherited disorder associated with
      recognised clinical features. Bleeding tendency was noticed in some of our
      patients, although this has not been reported before. We therefore studied this
      problem in all our WS patients and tried to postulate a possible pathogenesis. At
      the same time, a genetic linkage study provided evidence of locus heterogeneity
      of this syndrome and showed that the majority of our patients belong to the
      second WS locus identified in that study. Our study group consisted of 13 WS
      patients, belonging to WSF2 locus (group I). Controls consisted of 4 healthy
      siblings of WS patients (group II) and 7 diabetics who do not have WS (group
      III). Relevant clinical data were obtained, and a coagulation screen was carried
      out for all groups. All individuals in the three study groups have normal
      platelet count, thrombin time (TT), prothrombin time (PT), activated partial
      thromboplastin time (aPTT), clot retraction, Factor VIII activity (FVIIIc) and
      von Willebrand factor antigen (vWAg). Eleven of the WS patients have prolonged
      template bleeding time (BT) compared with both control groups. Patients with WS
      have a longer BT (mean 9.6 min, 95% CL 8.61-10.53 min) than the siblings group
      (mean 6.75 min, 95% CL 5.52-7.98 min) and the diabetic group (mean 5.49 min, 95%
      CL 4.56-6.42 min). The differences between the study group and controls are
      statistically significant, p = 0.02 and 0.0002, respectively. In the three
      groups, platelet aggregation studies were normal using adenosine diphosphate
      (ADP), ristocetin and epinephrine. Aggregation with collagen was either absent or
      impaired, with failure of secondary wave being noticed in 11 of the WS patients
      (85%) and normal in the control groups. The pathogenesis of this problem is not
      known, but could be due to an inhibitory effect of vWAgII, deficiency of
      thrombospondin or a defect in the platelet membrane GPIa/IIa. Bleeding diathesis
      is a new additional feature to the clinical spectrum of WS, which is probably a
      feature of the disorder WFS2 and not WFS1, as bleeding has never been reported in
      the latter. This provides further evidence for the phenotypic and genotypic
      heterogeneity of this complex disorder and may provide clues to the search for
      the second gene responsible for this phenotype.

PMID- 11317649
TI  - Manganese elevations in blood of children with congenital portosystemic shunts.
AB  - Magnetic response imaging has demonstrated increased signal intensities within
      the basal ganglia in patients with hepatic encephalopathy; the densities are
      considered to represent manganese deposition. We measured whole blood manganese
      concentrations in nine children with congenital portosystemic venous shunts
      detected by screening tests for galactosaemia. Beyond 1 year of age, these
      patients showed significantly higher manganese concentrations than controls (2.40
      +/- 0.43 versus 1.48 +/- 0.38 micrograms/dl; P = 0.0001). Four of the nine
      patients were studied by magnetic response imaging. T1-weighted images showed
      increased signal intensities in the basal ganglia of those four patients,
      suggesting manganese accumulation. CONCLUSION: Children with congenital
      portosystemic venous shunts showed manganese elevations in blood and magnetic
      response imaging changes in the basal ganglia. These children should avoid
      excessive manganese intake.

PMID- 11317650
TI  - Iodine deficiency during infancy and early childhood in Belgium: does it pose a
      risk to brain development?
AB  - Iodine deficiency is well documented in Belgium in adults including pregnant
      women, adolescents, schoolchildren, and neonates, but no data are available in
      the age group 6 months-3 years. We investigated the status of iodine nutrition in
      111 healthy subjects in this age group in an attempt to evaluate the risk of
      brain damage due to iodine deficiency in Belgium. In 244 causal urine samples
      collected in these subjects, the median concentration of iodine was 101
      micrograms/l vs 180-220 micrograms/l under normal conditions. The daily
      supplementation of the subjects with a physiological dose of 90 micrograms iodine
      was followed by a slow and progressive increase of urinary iodine, which reached
      a normal level only after a delay of about 30 weeks of therapy. This observation
      suggests that part of the supplement of iodine offered to the children was stored
      in their thyroid glands until the iodine content of the gland had reverted to
      normal, reflecting the state of hyperavidity of the thyroid for iodide
      characteristic of iodine deficiency. In conclusion, infants and young children in
      Belgium are as iodine deficient as all other age groups of the population and,
      consequently, are at risk of brain damage. This works further illustrates the
      need for systematic iodine supplementation of the population in Belgium.

PMID- 11317651
TI  - A 7-year-old girl with hip pain and leg weakness.

PMID- 11317652
TI  - Asymptomatic persistent pulmonary infiltrates in an immunocompetent boy with cat
      scratch disease.
AB  - We describe here an immunocompetent boy with fever, regional adenopathy,
      multifocal hepatosplenic granulomas, and high and increasing serum antibody
      titers for Bartonella henselae in whom diffuse bilateral reticulonodular
      pulmonary infiltrates developed in the absence of respiratory symptoms.

PMID- 11317653
TI  - The prevalence and diagnosis of lysosomal storage diseases in Poland.

PMID- 11317654
TI  - Lobar pulmonary interstitial emphysema in a premature infant on continuous
      positive airway pressure using nasal prongs.
AB  - Unilobar pulmonary interstitial emphysema may emerge in extremely low birth
      weight infants without mechanical ventilation but on continuous positive airway
      pressure using nasal prongs.

PMID- 11317655
TI  - Isolated recurrent pericarditis in a patient with familial Mediterranean fever.
AB  - Familial Mediterranean fever (FMF) should be kept in mind in the differential
      diagnosis of recurrent pericarditis and mutation analysis should be considered,
      especially in patients of Mediterranean origin.

PMID- 11317656
TI  - The role of viruses in type I diabetes: two distinct cellular and molecular
      pathogenic mechanisms of virus-induced diabetes in animals.
AB  - Type I (insulin-dependent) diabetes mellitus results from the progressive loss of
      pancreatic beta cells. Environmental factors are believed to play an important
      part in the development of Type I diabetes by influencing the penetrance of
      diabetes susceptibility genes. As one environmental factor, the virus has long
      been considered to play a part in this disease. To date 13 different viruses have
      been reported to be associated with the development of Type I diabetes in humans
      and in various animal models. The most clear and unequivocal evidence that a
      virus induces diabetes in animals comes from studies on the D variant of the
      encephalomyocarditis (EMC-D) virus in mice and the Kilham rat virus (KRV) in
      rats. The infection of genetically susceptible strains of mice with a high titre
      of EMC-D virus results in the development of diabetes within 3 days. This is
      largely due to the rapid destruction of beta cells by the replication of the
      virus within the beta cells. In contrast, the infection of mice with a low titre
      of EMC-D virus results in a limited replication of the virus before the induction
      of neutralizing anti-virus antibody and the subsequent recruitment of activated
      macrophages. The Src kinases, particularly hck, play an important part in the
      activation of macrophages and the subsequent production of tumour necrosis factor
      (TNF)-alpha, interleukin (IL)-1 beta and nitric oxide (NO), leading to the
      destruction of beta cells which results in the development of diabetes. The
      Kilham rat virus causes autoimmune diabetes in diabetes resistant (DR)-BB rats
      without infection of beta cells. The infection of DR-BB rats with KRV results in
      the disruption of the finely tuned immune balance of Th1-like CD45RC+CD4+ and Th2
      like CD45RC-CD4+ T cells, leading to the selective activation of beta-cell
      cytotoxic effector T cells.

PMID- 11317657
TI  - Epidemiology of type I diabetes mellitus in Switzerland: steep rise in incidence
      in under 5 year old children in the past decade.
AB  - AIMS/HYPOTHESIS: In this nationwide prospective study we wanted to verify the
      trend of increasing diabetes incidence data from our earlier retrospective
      analysis of the military registry of Swiss men. SUBJECTS AND METHODS: The data
      collection of newly diagnosed children in Switzerland at an age younger than 15
      years started in 1991. The countrywide survey used a small questionnaire which
      was sent back to the study centre. The questionnaire was anonymous and contained:
      hospital of diagnosis, initials, sex, birth date, date of diagnosis, residence,
      country of citizenship, and responsible physician. General data on the population
      were taken from publications of the Swiss Federal Statistical Office. RESULTS: A
      total of 941 children below the age of 15 years with newly diagnosed Type I
      (insulin-dependent) diabetes mellitus were collected (434 girls, 507 boys). The
      incidence in children aged 0 to 14 years rose significantly between 1991 and 1999
      with a yearly average increase of 5.1%. In the age group 0 to 4 years a more than
      four-fold increase in incidence from 2.4/100,000 per year to 10.5/100,000 per
      year (p = 0.0002) was recorded, whereas the age-specific incidence in the 5 to 9
      year-old and 10 to 14-year-old children did not change during the data collection
      period. The incidence was significantly higher in boys than in girls, whereas no
      difference was found between rural and urban populations.
      CONCLUSION/INTERPRETATION: The incidence of Type I diabetes is rising in children
      living in Switzerland but only the youngest age group of under 5 years of age is
      affected showing a large annual average increase of 23.8%.

PMID- 11317658
TI  - Feasibility of genetic and immunological prediction of type I diabetes in a
      population-based birth cohort.
AB  - AIMS/HYPOTHESIS: Population-wide genetic screening of susceptibility to
      multifactorial diseases will become relevant as knowledge of the pathogenesis of
      these diseases increases and preventive interventions are identified. METHODS:
      Feasibility and acceptance of neonatal genetic screening for Type I (insulin
      dependent) diabetes mellitus susceptibility and adherence of the at-risk children
      to frequent autoantibody follow-up were studied. Screening was offered to all
      families. The infants with HLA-DQB1 genotypes *02/*0302 and *0302/x (x not equal
      to *02, *0301, *0602) were invited to autoantibody follow-up. The children who
      developed signs of beta-cell autoimmunity were invited to a separate prevention
      trial. RESULTS: The parents of 31,526 babies born between November 1994 and April
      1999 (94.4% of those eligible) agreed to genetic screening. We found that 4651
      infants (14.8%) had increased genetic risk (2.5 to 15 times that of the general
      population) for Type I (insulin-dependent) diabetes mellitus, and 80% of them
      joined the autoantibody surveillance. At the age of 1, 2, 3 and 4 years, 74, 69,
      68 and 76% of the at-risk children, respectively, attended the follow-up. A total
      of 17 of the 22 children (77%) who were born during the study period and have
      developed diabetes carry the risk genotypes we currently use for screening.
      CONCLUSIONS/INTERPRETATION: Population-based screening of genetic susceptibility
      for Type I diabetes, linked with a possibility to participate later in a
      prevention trial, is highly accepted in Finland and identifies about 75% of those
      developing diabetes at an early age. Families adhere well to the frequent
      measurement of signs of beta-cell autoimmunity in the children at-risk.

PMID- 11317659
TI  - Cost-effectiveness analysis of intensive blood-glucose control with metformin in
      overweight patients with type II diabetes (UKPDS No. 51).
AB  - AIMS/HYPOTHESIS: To estimate the economic efficiency of intensive blood-glucose
      control with metformin compared with conventional therapy primarily with diet in
      overweight patients with Type II (non-insulin-dependent) diabetes mellitus.
      METHODS: Cost-effectiveness analysis based on patient level data from a
      randomised clinical controlled trial involving 753 overweight (> 120% ideal body
      weight) patients with newly diagnosed Type II diabetes conducted in 15 hospital
      based clinics in England, Scotland and Northern Ireland as part of the UK
      Prospective Diabetes Study. Subjects were allocated at random to an intensive
      blood-glucose control policy with metformin (n = 342) or a conventional policy
      primarily with diet (n = 411). The analysis was based on the cost of health care
      resources associated with metformin and conventional therapy and the estimated
      effectiveness in terms of life expectancy gained from within-trial effects.
      RESULTS: Intensive blood-glucose control with metformin produced a net saving of
      258 Pounds per patient (1997 United Kingdom prices) over the trial period (median
      duration of 10.7 years) due to lower complication costs, and increased life
      expectancy by 0.4 years (costs and benefits discounted at 6%).
      CONCLUSIONS/INTERPRETATION: As metformin is both cost-saving in the United
      Kingdom and extends life expectancy when used as first line pharmacological
      therapy in overweight Type II diabetic patients, its use should be attractive to
      clinicians and health care managers alike.

PMID- 11317660
TI  - Dose-response relation of liquid aerosol inhaled insulin in type I diabetic
      patients.
AB  - AIMS/HYPOTHESIS: The AERx insulin Diabetes Management system (AERx iDMS) is a
      liquid aerosol device that enables insulin to be administered to the peripheral
      parts of the lung. This study aimed to compare the pharmacokinetic and
      pharmacodynamic properties of insulin which is inhaled using AERx iDMS with
      insulin which is subcutaneously administered. METHODS: In total, 18 C-peptide
      negative patients with Type I (insulin-dependent) diabetes mellitus participated
      in this randomised, open-label, 5-period crossover trial. Human regular insulin
      was administered subcutaneously (0.12 U/kg body weight) or inhaled by means of
      the AERx iDMS (dosages 0.3, 0.6, 1.2, and 1.8 U/kg body weight). Thereafter
      plasma glucose was kept constant at 7.2 mmol/l for a 10-h period (glucose clamp
      technique). RESULTS: Inhaled insulin provided a dose-response relation that was
      close to linear for both pharmacokinetic (AUC-Ins(0-10 h); Cmax-Ins) and
      pharmacodynamic (AUC-GIR(0-10 h); GIRmax) parameters. Time to maximum insulin
      concentration (Tmax-Ins) and time to maximum glucose infusion rate (TGIRmax) were
      shorter with inhaled insulin than with subcutaneous administration. The
      pharmacodynamic system efficiency of inhaled insulin (AUC-GIR(0-6 h) was 12.7%
      (95% C.I.: 10.2-15.6). CONCLUSION/INTERPRETATION: The inhalation of soluble human
      insulin using the AERx iDMS is feasible and provides a clear dose response.
      Further long-term studies are required to investigate safety aspects, HbA1c
      values, incidence of hypoglycaemic events and the quality of life.

PMID- 11317661
TI  - Serum levels of the interferon-gamma-inducing cytokine interleukin-18 are
      increased in individuals at high risk of developing type I diabetes.
AB  - AIMS/HYPOTHESIS: Interleukin (IL)-18 is a cytokine primarily produced by
      macrophages and capable of inducing T lymphocyte synthesis of interferon (IFN)
      gamma. An up-regulated synthesis of IFN-gamma with consequential Type I cytokine
      dominance has been repeatedly shown in Type I (insulin-dependent) diabetes
      mellitus and thought to be involved in its pathogenesis. Because increased
      production of IFN-gamma could be secondary to a dysregulated synthesis of IL-18,
      we compared the circulating levels of IL-18 in patients with newly diagnosed Type
      I diabetes with those of non-diabetic first-degree relatives and healthy control
      subjects. METHODS: Serum samples were obtained from healthy control subjects,
      patients with newly diagnosed Type I diabetes, and their healthy first-degree
      relatives. The latter were subdivided into "low" and "high" risk prediabetics
      depending on whether they were negative or positive for two or more of the anti
      pancreatic autoantibodies ICA, GAD, IA-2 and IAA. Serum levels of IL-18 were
      measured by solid-phase ELISA. RESULTS: Interleukin (IL)-18 was above the
      detection limit of 25 pg/ml in 7 of 40 (17%) healthy control subjects, in 5 of 35
      (14%) patients and in 3 of 30 (10%) first-degree relatives at low risk of
      developing Type I diabetes. In contrast, IL-18 could be detected in 19 of 28
      (68%; p < 0.0001) relatives at high risk. The mean serum level of IL-18 was
      higher in these individuals when compared with the low-risk relatives, patients
      and control subjects. CONCLUSIONS/INTERPRETATION: IL-18 serum levels are
      increased selectively during the early, subclinical stage of Type I diabetes.

PMID- 11317662
TI  - Substituting dietary saturated for monounsaturated fat impairs insulin
      sensitivity in healthy men and women: The KANWU Study.
AB  - AIMS/HYPOTHESIS: The amount and quality of fat in the diet could be of importance
      for development of insulin resistance and related metabolic disorders. Our aim
      was to determine whether a change in dietary fat quality alone could alter
      insulin action in humans. METHODS: The KANWU study included 162 healthy subjects
      chosen at random to receive a controlled, isoenergetic diet for 3 months
      containing either a high proportion of saturated (SAFA diet) or monounsaturated
      (MUFA diet) fatty acids. Within each group there was a second assignment at
      random to supplements with fish oil (3.6 g n-3 fatty acids/d) or placebo.
      RESULTS: Insulin sensitivity was significantly impaired on the saturated fatty
      acid diet (-10%, p = 0.03) but did not change on the monounsaturated fatty acid
      diet (+2%, NS) (p = 0.05 for difference between diets). Insulin secretion was not
      affected. The addition of n-3 fatty acids influenced neither insulin sensitivity
      nor insulin secretion. The favourable effects of substituting a monounsaturated
      fatty acid diet for a saturated fatty acid diet on insulin sensitivity were only
      seen at a total fat intake below median (37E%). Here, insulin sensitivity was
      12.5% lower and 8.8% higher on the saturated fatty acid diet and monounsaturated
      fatty acid diet respectively (p = 0.03). Low density lipoprotein cholesterol
      (LDL) increased on the saturated fatty acid diet (+4.1%, p < 0.01) but decreased
      on the monounsaturated fatty acid diet (MUFA) (-5.2, p < 0.001), whereas
      lipoprotein (a) [Lp(a)] increased on a monounsaturated fatty acid diet by 12% (p
      < 0.001). CONCLUSIONS/INTERPRETATION: A change of the proportions of dietary
      fatty acids, decreasing saturated fatty acid and increasing monounsaturated fatty
      acid, improves insulin sensitivity but has no effect on insulin secretion. A
      beneficial impact of the fat quality on insulin sensitivity is not seen in
      individuals with a high fat intake (> 37E%).

PMID- 11317663
TI  - Apoptosis and disease progression in the spontaneously diabetic BB/S rat.
AB  - AIMS/HYPOTHESIS: Type I (insulin-dependent) diabetes mellitus is an autoimmune
      disease culminating in pancreatic beta-cell destruction. A role for apoptosis in
      this destruction has been suggested, although controversy exists over the
      identity of the apoptotic cells and the time of onset of apoptosis. This study
      investigates the extent and timing of islet cell apoptosis in vivo in the
      spontaneously diabetic BB/S rat. METHODS: Pancreatic biopsies were taken from 30
      diabetes-prone and 6 diabetes-resistant BB/S rats matched for age. Animals were
      serially biopsied before, during and after development of diabetes and apoptotic
      cells analysed in serial sections. The diabetes-prone group included animals (n =
      6) that had insulitis but did not develop diabetes. RESULTS: Apoptosis was not
      detected in any pancreatic sections from diabetes resistant animals at any age
      investigated or from any animal before 50 days of age. By 68 days, apoptosis was,
      however, detectable in both the diabetes-prone group and in the group that had
      insulitus but did not develop diabetes and this correlated with a decrease in
      pancreatic insulin staining and a development of insulitis. There was a further
      increase in apoptosis in the diabetes-prone group at 85 days, which coincided
      with the time of onset of diabetes (84 days). In addition, there was a sixfold
      increase in intra-islet apoptosis between 68 and 85 days in the diabetes-prone
      group and at 85 days intra-islet apoptosis was threefold higher in the diabetes
      prone group than in the group that had insulitus but did not develop diabetes. At
      107 days, apoptosis (total and intra-islet) was higher in the group that had
      insulitus but did not develop diabetes (OND-DP) than in either the diabetes
      resistant (DR) or diabetes-prone (DP) groups. CONCLUSION/INTERPRETATION: We have
      shown significant islet cell apoptosis in the pancreas of diabetes-prone BB/S
      rats, which coincides with the appearance of insulitis and the onset of diabetes.
      We have also detected differences in the levels of apoptosis between diabetic and
      non-diabetic animals and suggest that such differences could be an important
      determinant of disease progression in this animal model of Type I diabetes.

PMID- 11317664
TI  - Monocyte chemoattractant protein-1 is expressed in pancreatic islets from
      prediabetic NOD mice and in interleukin-1 beta-exposed human and rat islet cells.
AB  - AIMS/HYPOTHESIS: Monocyte chemoattractant protein-1 (MCP-1) attracts monocytes
      and T lymphocytes, and could thus contribute to mononuclear cell infiltration in
      Type I (insulin-dependent) diabetes mellitus. Cytokines induce MCP-1 mRNA
      expression in pancreatic rat beta cells. To investigate this issue, we analysed
      the signal transduction for IL-1 beta-induced MCP-1 expression in rat beta cells
      and in vitro MCP-1 mRNA expression and protein release by human islets as well as
      in vivo islet MCP-1 mRNA expression in prediabetic non-obese diabetic mice.
      METHODS: Fluorescence-activated cell sorting-purified rat beta cells were
      cultured for 6 h with IL-1 beta (30 U/ml) or MAPK inhibitors or both. Human
      islets were cultured for 6-72 h with the cytokines IL-1 beta, IFN-gamma or the
      inducible nitric oxide synthase (iNOS) inhibitor NG-methyl-L-arginine or both. We
      measured MCP-1 mRNA by RT-PCR and protein by ELISA. The MCP-1 mRNA expression in
      islets from male and female non-obese diabetic mice (2-12 weeks of age) was
      measured by real time reverse transcription-polymerase chain reaction (RT-PCR).
      RESULTS: Interleukin-1 beta induced MCP-1 mRNA expression in rat beta cells, with
      a maximum induction after 6 h. A combination of p38 and ERK1/2 inhibitors
      decreased MCP-1 expression by 70%. IL-1 beta induced both MCP-1 mRNA expression
      and a threefold increase in medium MCP-1 protein accumulation in human islet
      cells. This effect was not prevented by iNOS blockers. In vivo there was an age
      related increase in MCP-1 mRNA expression in islets from male and female non
      obese diabetic mice, reaching a peak at 8 weeks. CONCLUSIONS/INTERPRETATION: In
      rat and human islet cells MCP-1 mRNA is induced by IL-1 beta. Both ERK1/2 and p38
      MAPK, but not nitric oxide, contribute to MCP-1 expression. In non-obese diabetic
      mice MCP-1 mRNA expression increases with age, peaking at the early phases of
      insulitis. The production of MCP-1 by pancreatic beta cells could contribute to
      the recruitment of mononuclear cells into pancreatic islets in early Type I
      diabetes.

PMID- 11317666
TI  - Abnormal light scattering detected by confocal biomicroscopy at the corneal
      epithelial basement membrane of subjects with type II diabetes.
AB  - AIMS/HYPOTHESIS: Abnormalities of the basement membrane are thought to contribute
      to the complications of diabetes. The suitability of the cornea for detecting
      such abnormalities was assessed by determining its light-scattering index, a
      quantitative measure of tissue reflectivity in the basement membrane zone, with a
      confocal biomicroscope. METHODS: The light-scattering index was measured in 65
      subjects with Type II (non-insulin-dependent) diabetes mellitus and 18 control
      subjects and was evaluated for its possible relation to the stage of diabetic
      retinopathy. Diabetic retinopathy was staged by ophthalmoscopic examination as
      non-diabetic (NDR), simple (SDR), preproliferative (PPDR), or proliferative
      (PDR). RESULTS: Examination of the cornea layer-by-layer with a confocal
      biomicroscope did not show any marked differences in morphology between diabetic
      and control subjects. The LSI (mean +/- SD) was 0.81 +/- 0.13, 0.87 +/- 0.09,
      0.90 +/- 0.09, 0.90 +/- 0.13, and 1.02 +/- 0.25 in control subjects and in
      diabetic subjects with NDR, SDR, PPDR, or PDR, respectively; the light-scattering
      index of diabetic subjects with PDR was significantly greater than that of the
      control subjects (p = 0.001). An LSI greater than 1.0 was detected in 5.6, 6.3,
      15.0, 15.4, and 50.0% of control subjects and of patients with NDR, SDR, PPDR, or
      PDR, respectively; the percentage of subjects with an LSI greater than 1.0 was
      significantly increased in diabetic patients with PDR than for control subjects.
      CONCLUSION/INTERPRETATION: These results suggest that the LSI increases with the
      stage of diabetic retinopathy, and that measurement of corneal light scattering
      could provide an index of basement membrane abnormality in people with diabetes.

PMID- 11317665
TI  - Close relation of fasting insulin-like growth factor binding protein-1 (IGFBP-1)
      with glucose tolerance and cardiovascular risk in two populations.
AB  - AIMS/HYPOTHESIS: Insulin resistance/hyperinsulinaemia is implicated in the
      development of cardiovascular disease and diabetes but its role and causal
      pathways are not clear. We tested the hypothesis that the insulin-like growth
      factor system is independently associated with cardiovascular risk within
      susceptible populations based on previous reports of the links between low
      circulating insulin-like growth factor binding protein-1 concentrations and
      increased macrovascular disease in Type II (non-insulin-dependent) diabetes
      mellitus. METHODS: In a population-based study 272 subjects (142 subjects of
      European and 130 Pakistani of origin) underwent a 75 g oral glucose tolerance
      test and standardised anthropometry. Fasting concentrations of insulin-like
      growth factor binding protein-1 (IGFBP-1), insulin-like growth factor-I (IGF-I),
      insulin-like growth factor-II (IGF-II), intact insulin and lipids were measured
      and were related to 2-h glucose tolerance test status. Insulin sensitivity was
      calculated using the homeostasis model assessment (HOMA). RESULTS: Insulin-like
      growth factor binding protein-1 was significantly lower in subjects with impaired
      glucose tolerance when compared with normal glucose tolerance in both ethnic
      groups (Europeans F = 6.7, p = 0.002 and Pakistanis F = 4.4, p = 0.01). Multiple
      linear regression modelling showed that insulin-like growth factor binding
      protein-1 was independently associated with 2-h glucose (beta = 0.16, p = 0.009)
      and logistic regression indicated a 40% reduction in risk of impaired glucose
      tolerance for every 2.7 ng/ml increase in the insulin-like growth factor binding
      protein-1 concentration [odds ratio 0.6 (CI = 0.49-0.71), p = 0.001)]. In
      addition, insulin-like growth factor binding protein-1 was significantly
      correlated negatively with several established cardiovascular factors, and
      positively with insulin sensitivity. CONCLUSIONS/INTERPRETATION: Insulin-like
      growth factor binding protein-1 is closely related to risk factors for diabetes
      and cardiovascular disease in people of European and Pakistani origin. It has
      potential use as a marker of (hepatic) insulin resistance in clinical
      intervention studies and further implicates the insulin-like growth factor system
      in the development of macrovascular disease.

PMID- 11317667
TI  - Cerebral metabolism in streptozotocin-diabetic rats: an in vivo magnetic
      resonance spectroscopy study.
AB  - AIMS/HYPOTHESIS: It is increasingly evident that the brain is another site of
      diabetic end-organ damage. The pathogenesis has not been fully explained, but
      seems to involve an interplay between aberrant glucose metabolism and vascular
      changes. Vascular changes, such as deficits in cerebral blood flow, could
      compromise cerebral energy metabolism. We therefore examined cerebral metabolism
      in streptozotocin-diabetic rats in vivo by means of localised 31P and 1H magnetic
      resonance spectroscopy. METHODS: Rats were examined 2 weeks and 4 and 8 months
      after diabetes induction. A non-diabetic group was examined at baseline and after
      8 months. RESULTS: In 31P spectra the phosphocreatine:ATP,
      phosphocreatine:inorganic phosphate and ATP:inorganic phosphate ratios and
      intracellular pH in diabetic rats were similar to controls at all time points. In
      1H spectra a lactate resonance was detected as frequently in controls as in
      diabetic rats. Compared with baseline and 8-month controls 1H spectra did,
      however, show a statistically significant decrease in N-acetylaspartate:total
      creatine (-14% and -23%) and N-acetylaspartate:choline (-21% and -17%) ratios
      after 2 weeks and 8 months of diabetes, respectively. CONCLUSION/INTERPRETATION:
      No statistically significant alterations in cerebral energy metabolism were
      observed after up to 8 months of streptozotocin-diabetes. These findings indicate
      that cerebral blood flow disturbances in diabetic rats do not compromise the
      energy status of the brain to a level detectable by magnetic resonance
      spectroscopy. Reductions in N-acetylaspartate levels in the brain of STZ-diabetic
      rats were shown by 1H spectroscopy, which could present a marker for early
      metabolic or functional abnormalities in cerebral neurones in diabetes.

PMID- 11317668
TI  - Heterogeneity of type I diabetes: analysis of monozygotic twins in Great Britain
      and the United States.
AB  - AIMS: To determine the risk, hazard rate and factors affecting progression to
      diabetes in monozygotic twins of patients with Type I (insulin-dependent)
      diabetes mellitus. METHODS: Prospective analysis was done of two cohorts of non
      diabetic monozygotic twins of patients with Type I diabetes from Great Britain (n
      = 134) and the United States (n = 53). RESULTS: The diabetes-free survival
      analysis was similar between both cohorts (p = 0.6). The combined survival
      analysis (n = 187, median follow-up = 17.7 years, range = 0.01-57) at 40 years of
      discordance estimated a 39% probability of diabetes for the initially discordant
      twin. Survival analysis with left truncation of data estimated that probability
      to be 50%. For twins who became concordant (n = 47), the median discordance time
      was 4.2 years (range 0.4 to 39), exceeding 15 years in 23.4%. Twins of probands
      diagnosed at 24 years of age or younger had a 38% probability of diabetes by 30
      years of discordance, compared with 6% for twins of probands diagnosed after 24
      years of age (p = 0.004). The twins of probands diagnosed before 15 years of age
      had the highest diabetes hazard rate in the first discordance year, decreasing
      thereafter. By survival analysis, diabetes risk was higher in twins who were
      heterozygous for DR3-DQ2 and DR4-DQ8 than in twins with neither DR3-DQ2 nor DR4
      DQ8 (p < 0.05). CONCLUSION/INTERPRETATION: Monozygotic twins of patients with
      Type I diabetes from two different countries had similar rates of progression to
      diabetes. Whereas most twins did not develop diabetes, 25% of the twins who
      progressed did so after more than 14 years of discordance. An age-related
      heterogeneity was observed, with higher progression to diabetes for twins of
      patients diagnosed at a younger age.

PMID- 11317669
TI  - A locus affecting obesity in human chromosome region 10p12.
AB  - AIMS/HYPOTHESIS: Obesity is a complex trait influenced by multiple genes. We
      evaluated linkage in three regions of human chromosome 10 previously linked to
      obesity-related phenotypes. METHODS: We conducted non-parametric linkage analysis
      of obesity-related phenotypes in cohorts of 170 European-American and 43 African
      American families having extremely obese and normal weight subjects. RESULTS: We
      found support for linkage of an obesity phenotype (BMI > or = 27 kg/m2) in both
      cohorts, as well as in a combined analysis (European-American cohort, Z = 1.90, p
      = 0.03; African-American cohort, Z = 2.25, p = 0.014; combined cohort, Z = 2.55,
      p = 0.005). CONCLUSION/INTERPRETATION: These results confirm previous reports of
      linkage in French and German families. The consistency of results across these
      four cohorts supports the localization of a quantitative trait locus influencing
      obesity to human chromosome region 10p12.

PMID- 11317670
TI  - The G972R variant of the insulin receptor substrate-1 (IRS-1) gene, body fat
      distribution and insulin-resistance.
AB  - AIMS/HYPOTHESIS: Insulin resistance is recognised as the core factor in the
      pathogenesis of Type II (non-insulin-dependent) diabetes mellitus, hypertension
      and atherosclerosis. Several studies indicate the possible role of mutations of
      the insulin receptor substrate-1 (IRS-1) gene in the pathogenesis of insulin
      resistance and suggest a possible interaction between the IRS-1 gene and obesity,
      either by an effect on the development of obesity or by causing or aggravating
      the obesity-associated insulin resistance. Therefore, the prevalence of the G972R
      mutation of the IRS-1 gene was compared in 157 non-diabetic obese subjects (BMI >
      30 m/kg2) and in 157 lean subjects (BMI < 28 m/kg2). By investigating the
      relation between this IRS-1 mutation, measures of obesity and metabolic
      parameters, we explored the possible influence of this mutation on body fat
      distribution and insulin resistance. METHODS: The G972R mutation was detected by
      PCR amplification and BstN-1 restriction enzyme digestion. Data were analysed by
      univariate and multivariate analysis. RESULTS: The G972R allele was significantly
      more frequent in obese subjects than in lean subjects (p < 0.002); however, no
      difference was found between centrally and peripherally obese subjects. Obese
      G972R carriers had significantly higher BMI (p < 0.001), fasting insulin (p <
      0.001), triglycerides (p < 0.03) and HOMAIR (p < 0.001) than obese non-carriers.
      No differences were observed between G972R carriers and non-carriers among
      control subjects. Multivariate analysis confirmed that the IRS-1 G972R mutation
      was significantly and independently associated with reduced insulin sensitivity
      (p < 0.009) in the obese group. CONCLUSION/INTERPRETATION: The G972R mutation of
      the IRS-1 gene associates with obesity, but not with fat distribution, in this
      Italian cohort, and within the obese subjects this IRS-1 variant strongly
      associates with metabolic parameters suggesting greater insulin-resistance. These
      findings indicate a possible interaction between the IRS-1 variant and obesity in
      worsening insulin sensitivity.

PMID- 11317671
TI  - A polymorphism in the 5' untranslated region and a Met229-->Leu variant in exon 5
      of the human UCP1 gene are associated with susceptibility to type II diabetes
      mellitus.
AB  - AIMS/HYPOTHESIS: The cumulative effects of several thrifty factors could
      contribute to the pathogenesis of Type II (non-insulin-dependent) diabetes
      mellitus. We screened the human UCP1 gene (UCP1) for polymorphisms associated
      with susceptibility to Type II diabetes. METHODS: By using PCR and single-strand
      conformation polymorphism analysis, UCP1 were screened for mutations in 25 Type
      II diabetic subjects and 25 healthy control subjects. The allele frequencies of
      the detected polymorphisms were determined by PCR and restriction fragment length
      polymorphism analysis in 320 diabetic subjects and 250 control subjects. RESULTS:
      An A-->C transition in the 5' untranslated region (UTR) of exon 1 (112 bp
      upstream of the translation initiation codon) and a Met229-->Leu variant were
      detected. The allele frequencies for the C variant and for the Leu229 variant
      were higher in the Type II diabetic group than in the control group (p = 0.017
      and p = 0.038, respectively). These polymorphisms were in linkage disequilibrium
      (p < 0.00001). Luciferase assay showed that the former variant in the 5' UTR may
      affect the promoter activity of UCP1. CONCLUSION/INTERPRETATION: Both the A-->C
      polymorphism and the Met229-->Leu polymorphism of UCP1 are in linkage
      disequilibrium and could be one of the diabetes associated single nucleotide
      polymorphisms (SNPs).

PMID- 11317673
TI  - Splice site mutation in the hepatocyte nuclear factor-1 beta gene, IVS2nt + 1G >
      A, associated with maturity-onset diabetes of the young, renal dysplasia and
      bicornuate uterus.

PMID- 11317672
TI  - Effect of dexamethasone on adipocyte differentiation markers and tumour necrosis
      factor-alpha expression in human PAZ6 cells.
AB  - AIMS/HYPOTHESIS: Adipose tissue-derived tumour necrosis factor-alpha (TNF-alpha)
      has been implicated in the insulin resistance observed in animal models of
      obesity. Moreover, TNF-alpha has inhibitory effects on adipocyte differentiation.
      Glucocorticoids play important roles in the regulation of insulin sensitivity and
      adipose tissue distribution. We therefore studied the effect of dexamethasone on
      TNF-alpha expression and adipocyte differentiation in human PAZ6 cells. METHODS:
      The expression of TNF-alpha and adipocyte differentiation markers was assessed by
      reverse-transcription polymerase chain reaction in PAZ6 cells. RESULTS: In cells
      cultured for 15 days in the presence of dexamethasone, adipocyte differentiation
      marker expression was higher and TNF-alpha expression was lower than in cells
      cultured in the absence of dexamethasone. The presence of dexamethasone was
      necessary during the whole period of differentiation because removal of
      dexamethasone during the second week resulted in poorly differentiated adipocytes
      that express higher levels of TNF-alpha. Dexamethasone also reduced TNF-alpha
      expression during early stages of differentiation. The use of a TNF-alpha
      neutralising antibody showed, however, that endogenously-produced TNF-alpha did
      not play an important part in the control of PAZ6 cell differentiation. During
      early stages of adipocyte differentiation, dexamethasone induced the expression
      of the transcription factors PPAR gamma (peroxisome proliferator activated
      receptor gamma) and C/EBP alpha (CCAAT/enhancer binding protein alpha) while
      inhibiting the expression of the inhibitor of DNA binding Id2.
      CONCLUSION/INTERPRETATION: The effect of dexamethasone on human adipocyte
      differentiation is not mediated by reduction of TNF-alpha expression but more
      likely by regulation of the expression of nuclear factors such as PPAR gamma,
      CEBP alpha and Id2.

PMID- 11317674
TI  - C peptide and insulin do not influence plasma semicarbazide-sensitive amine
      oxidase activity.

PMID- 11317675
TI  - Mitochondria from human trophoblast and embryonic liver cells are resistant to
      hyperglycaemia-associated high-amplitude swelling.

PMID- 11317676
TI  - Alteration of collagen network and negative charge of articular cartilage surface
      in the early stage of experimental osteoarthritis.
AB  - Forty-eight mature male Japanese white rabbits were subjected to unilateral
      resection of a segment of the gluteal muscles at the sacral origin and a section
      of infrapatellar ligament. Animals were killed at 1, 2, 4, and 8 weeks
      postoperatively, and the articular cartilage of the femoral heads was evaluated.
      The collagen fibrillar network of the articular surface was observed by scanning
      electron microscopy (SEM) using microdissection by ultrasonication. Cationized
      ferritin (CF) was used for the labeling of negative charges on the articular
      surfaces and the thickness of CF layers was observed under the transmission
      electron microscope. Metachromasia of the matrix decreased remarkably at 4 weeks
      postoperatively, and fibrillation of the articular surface was evident at 8 weeks
      postoperatively. Derangement and rupture of the collagen network developed as
      early as 1 week after surgery. The thickness of the CF layer significantly
      decreased at 4 weeks postoperatively. This study confirms that alterations of the
      articular surface, such as derangement of the collagen network and loss of the
      negative charge, are some of the earliest changes in osteoarthritis. In addition,
      application of ultrasonication with proper frequencies to the articular cartilage
      effects an optimal removal of mucus, with the consequent exposure of a well
      preserved articular surface for SEM study.

PMID- 11317677
TI  - Lower limb amputation for diabetic foot.
AB  - We amputated 35 limbs of 27 patients with diabetic foot from March 1988 to March
      1998. The mean age of the patients at the time of operation was 67 years, and the
      mean follow-up period was 27 months. Thirteen patients died in the period from 1
      day to 39 months after the operation. All patients suffering from diabetic foot
      were referred to our department for surgical procedures after failure of
      conservative treatment conducted elsewhere. Their feet were classified into grade
      2-3 in 18 limbs, grade 4-5 in 11 limbs, and gangrene of the lower leg and entire
      foot in 2 limbs, as classified by the Wagner system. Two patients had cellulitis
      of the foot and two other limbs had infectious gonarthritis. All patients had
      type 2 diabetes with poor blood sugar control, and 90% were treated by insulin.
      All patients suffered from diabetic neuropathy. Half of the patients were put on
      hemodialysis because of diabetic nephropathy. More than 60% of the patients
      suffered from arteriosclerosis obliterans. The amputation level of the limb was
      determined by skin thermography, but the patient's will was critical. The initial
      amputation levels were: debridement and synovectomy in 4 limbs, toe and digital
      ray in 15 limbs, transmetatarsal in 3 limbs, transtibial in 9 limbs, transfemoral
      amputations in 4 limbs. Upper level reamputation was conducted on 15 limbs.
      Logistic regression analysis revealed that lower temperature of the amputation
      site, being female, and being elderly were significant risk factors in
      reamputation. Skin thermography was one of the effective determinants of
      amputation level, in order to avoid reamputation.

PMID- 11317678
TI  - Inability of transforming growth factor-beta 1, combined with a bioabsorbable
      polymer paste, to promote healing of bone defects in the rat distal femur.
AB  - The ability of transforming growth factor-beta 1 (TGF-beta 1) to promote bone
      formation suggests that it may have potential as a therapeutic agent in bone
      defects. However, there still exists a need for an effective method of delivering
      TGF-beta 1 to the site of an osseous defect. In the present study, TGF-beta 1 was
      embedded in a bioabsorbable polymer paste (a blend of an L-lactide oligomer and a
      copolymer of epsilon-caprolactone and DL-lactide). The release of TGF-beta 1 from
      the polymer paste was examined in vitro with an enzyme-linked immunosorbent
      assay, which showed sustained release of active TGF-beta 1 over a 7-day period.
      Further, the polymer paste was used to fill a bone defect in the rat distal
      femur. The amount of TGF-beta 1 per rat was 50 micrograms, while in a control
      group we used an identical polymer paste without the growth factor. After a
      follow-up of 1 week and 3 weeks, the femurs were examined radiographically,
      histologically, histomorphometrically, microradiographically, and were also used
      for tetracycline-labeling studies. TGF-beta 1 did not enhance healing of the bone
      defect. A combination of growth factors would probably be a more potent
      osteoinductor than TGF-beta 1 alone.

PMID- 11317679
TI  - The nail-insertion point in unreamed tibial nailing and its influence on the
      axial malalignment in proximal tibial fractures.
AB  - The consequence of choosing a point of insertion for the nail (i.e. medial or
      lateral of the lig. patellae) in unreamed tibial nailing (AO unreamed tibial
      nail, UTN) was studied in 22 formaldhyde-fixed tibiae. A lateral osteotomy at the
      transition from the first to the second fifth of the tibia was used as a model
      for the fracture. A nail insertion point medial of the lig. patellae caused a
      valgus deformity, combined with a shift of the distal fragment to the medial
      side. A lateral point of entry resulted in a varus deformity, together with a
      lateral shift of the distal fragment. Our results show that the insertion point
      of the nail is important for the alignment of the axis. Choosing a different
      point for the insertion of the nail can be useful in operative correction of
      malalignment of the tibia.

PMID- 11317680
TI  - The long-term (8-12 years) results of valgus and lengthening osteotomy of the
      femoral neck.
AB  - Shortening of the femoral neck and proximal displacement of the greater
      trochanter are the principal complications following avascular necrosis of the
      capital epiphysis head in early childhood. We report here the long-term follow-up
      of a series of osteotomies performed to lengthen the femoral neck and thus to
      restore the normal anatomy and function of the hip joint. Out of a sample of 24
      patients, 15 (62.5%) were reviewed at the end of a mean follow-up of 10 years and
      2 months. Fourteen of them (93.3%) had originally complained of pain on walking
      which varied in severity. After the operation, five were free from pain at the
      end of the follow-up, 9 still experienced pain on walking, and 1 also reported
      pain at rest. Before the operation, a positive Trendelenburg's sign was found in
      8 of the patients. This was still present in 2 at follow-up. The average
      perpendicular distance from the center of the femoral head to a horizontal plane
      passing through the tip of the greater trochanter (the centro-trochanteric
      distance) was reduced from 33 mm to 7 mm. Apart from correcting the anatomical
      deformity, it is suggested that this operation may well provide lasting relief
      from pain and increase the power of the abductor muscles. It may also delay the
      onset of osteoarthritic change and in this way postpone the necessity for an
      endoprosthesis.

PMID- 11317681
TI  - The value of desoxypyridinoline in the diagnostics of loosened arthroplasty.
AB  - According to several reports in the last few years, desoxypyridinoline (Dpd) in
      urine increases significantly in cases of loosened arthroplasty. Therefore, this
      marker was suggested as useful in the diagnostics of implant loosening. In this
      study, the level of Dpd was determined in 69 patients with arthroplasty of the
      hip or the knee joint. Thirty-four of these patients received revision surgery
      following implant loosening. In 35 of these 69 patients, there were no clinical
      or radiological signs of loosening (control group). The mean age of the patients
      with loosened implants (22 women, 13 men) was 67.9 years and of the control group
      (22 women, 12 men) 66.9 years. In the group with arthroplastic loosening, as well
      as in the control group, 14 patients had increased levels of Dpd. There were 20
      patients in the group with loosened arthroplasty and 19 patients in the control
      group that had normal levels of Dpd. The female patients had a mean Dpd level of
      8.6 nmol/mmol creatinine (4.3-24 nmol/mmol creatinine) in the urine in cases of
      loosening and 10.1 nmol/mmol creatinine (2-33 nmol/mmol creatinine) in the
      control group. The male patients had a mean Dpd level of 7.8 nmol/mmol creatinine
      (3.2-19.2 nmol/mmol creatinine) in the urine in cases of loosening and 5.8
      nmol/mmol creatinine (0.3-11.7 nmol/mmol creatinine) in the control group. In
      conclusion there was no significant increase in Dpd in patients with implant
      loosening compared with the control group. Furthermore, older patients often
      suffer from diseases causing increased bone resorption that may falsify the test
      results. We cannot confirm that Dpd is helpful in the diagnostics and screening
      of implant loosening.

PMID- 11317682
TI  - Midshaft fractures of the clavicle with a shortening of more than 2 cm predispose
      to nonunion.
AB  - Up to 15% of all fractures involve the clavicle. Nonunion of the clavicle is a
      rare complication after conservative treatment. It mainly presents as pain at the
      fracture site and a limited range of motion of the shoulder. The purpose of this
      study is to define a certain type of fracture of the clavicle that is predisposed
      to malunion and therefore should be treated surgically after failure of
      conservative treatment. Thirty-nine patients with delayed or malunion of the
      clavicle were analyzed. There were 13 women and 26 men. The average age of the
      male patients was 36.4 years (range 20-59 years) and of the female patients, 43.6
      years (range 18-55 years). The mean follow-up period was 2.3 years (range 6
      months to 4.2 years). All of them were treated surgically. There were 33 Allman I
      fractures and 6 Allman II fractures. Of the Allman I fractures, 30 (91%) were
      shortened by at least 2 cm. Allman I fractures were treated using a
      reconstruction plate or a dynamic compression plate in combination with bone
      grafting. The time of operation after fracture ranged from 6 weeks to 8.5 years
      (average 9.8 months). Pain at the fracture site was the leading symptom in all
      patients. At 6 months after the operation, 38 patients were free of pain with an
      unlimited range of motion of the shoulder. One patient (2.6%) complained of a
      slight weakness on the operated site. One fracture failed to unite (2.6%) and had
      to be replated. There were no refractures, infections, vessel or nerve lesions.
      To conclude, in Allman I fractures with a shortening of more than 2 cm, we
      recommend operative treatment in symptomatic patients if there are no signs of
      callus formation after 6 weeks.

PMID- 11317683
TI  - Results of flexor tendon repair of the hand by the motion-stable wire suture by
      Towfigh.
AB  - We compared the motion-stable wire suture by Towfigh (MSWST) with a modified
      Kessler suture (MKS) by following up flexor tendon repairs (MSWST, n = 21/39
      digits; MKS, n = 20/31 digits). For MSWST we found 31 (79.5%) "excellent", 3
      (7.7%) "good", and 5 (12.8%) "fair" results, when using the scoring system of
      Buck-Gramcko. In 3 (14.3%) patients the MSWST had to be removed owing to local
      irritation. In a further 3 (14.3%) patients, this was done when secondary
      tenolysis was necessary. The latter was also performed in 4 (20.0%) patients in
      whom the MKS was used. Here we found 23 (74.2%) excellent, 7 (22.6%) good, and 1
      (3.2%) fair result. The statistical evaluation of the data concerning the
      patients' age, sex, the involved zone, the side, and the functional outcome did
      not reveal a significant difference (P < 0.05) between both groups and the chosen
      type of repair. The results of MSWST and MKS are similar, but MSWST allows early
      motion therapy without a splint or rubber-band protection.

PMID- 11317684
TI  - Hypoxia-inducible factor-1 activation and cyclo-oxygenase-2 induction are early
      reperfusion-independent inflammatory events in hemorrhagic shock.
AB  - Hemorrhagic shock (HS) initiates an inflammatory response that includes increased
      expression of inducible nitric oxide synthase (iNOS) and production of
      prostaglandins. Induction of iNOS during the ischemic phase of HS may involve the
      activation of the hypoxia-inducible factor-1 (HIF-1). Increased expression of
      cyclooxygenase-2 (COX-2) during HS contributes to prostaglandin production. The
      aim of this study was to determine whether the ischemic phase of HS results in
      the activation of HIF-1 and the induction of COX-2. The lungs of rats subjected
      to HS demonstrated a twofold increase in HIF-1 activation (P < 0.01) and a 7.4
      fold increase in expression of COX-2 mRNA (P < 0.01) compared with sham controls.
      The upregulation of iNOS and COX-2 during ischemia are two important early
      response genes that promote the inflammatory response and may contribute to organ
      damage through the rapid and exaggerated production of nitric oxide and
      prostaglandins.

PMID- 11317686
TI  - An individualized approach for the implantation of a humeral prosthesis with the
      proper retroversion in fractures.
AB  - We applied a new methodology in 7 patients with a fracture of the upper humeral
      head that required hemiarthroplasty, to implant a humeral prosthesis with an
      individualized posterior version. Our goal was to determine preoperatively the
      distance from the posterior edge of the bicipital groove where the lateral fin of
      the humeral prosthesis should sit, in order to reproduce the individual
      retroversion during surgery. Using three computed tomography scan sections of the
      upper humerus and image processing software, we estimated the above-mentioned
      distance in the sound humerus and implanted the prosthesis in each patient
      accordingly. The differences in retroversion between the left and right humeral
      heads permit a better approximation to normal applying this methodology than
      inserting the prosthesis in a standard retroversion.

PMID- 11317685
TI  - Immunohistochemical characterization of the perivascular infiltrate cells in
      tissues adjacent to stainless steel implants compared with titanium implants.
AB  - Metallic orthopaedics implants are composed of elements that are known to be skin
      sensitizers in the general population. In this study, we analyzed the cells of
      perivascular infiltration in the tissue adjacent to titanium (n = 23) and steel
      (n = 8) implants after explantation of the metals by immunohistochemical methods.
      The following panel of monoclonal antibodies were used as parameters: CD 1a
      (Langerhans cells), CD 4 (T-helper cells), CD 8 (T-suppressor cells), CD 11c
      (monocytes and macrophages), CD 45 RO (memory cells), CD 45 RA (naive cells),
      eosinophil cationic proteins (ECP), neutrophil elastase, and HLA-DR. The number
      of perivascular total cells did not differ significantly. All cells were
      identified in both metal subgroups, but a statistical difference was not seen in
      the above-mentioned parameters. We conclude that sensitization to metals is
      possible in the tissue adjacent to steel and titanium implants, because all cells
      which play an important role in allergic delayed-type hypersensitivity (type IV)
      reactions are present. This phenomenon may be called a 'pre-sensitization' phase,
      because no sensitization or allergic reactions were seen in our cases. Second, in
      the present study, a statistical difference was not seen in the number of
      infiltrate cells in the tissue adjacent to steel compared with titanium implants.

PMID- 11317687
TI  - Bipartite median nerve with a double compartment within the transverse carpal
      canal.
AB  - An anomaly of the median nerve in which there is a division into two branches at
      the level of the distal third of the forearm is reported. This case was unique in
      that the ulnar branch of the median nerve passed through a separate compartment
      within the transverse carpal ligament. It was necessary to decompress both
      branches of the nerve when releasing the carpal canal.

PMID- 11317688
TI  - Irreducible open dorsal dislocation of the proximal interphalangeal joint.
AB  - Dislocations of the proximal interphalangeal joint rarely present a problem in
      reduction. We report a case of dorsal dislocation in which attempts at reduction
      by manipulation were not successful. A probable mechanism is discussed. In most
      cases of such injury, the flexor tendons should be elevated by a probe to allow
      replacement of the head of the proximal phalanx.

PMID- 11317689
TI  - A young athlete with myositis ossificans of the neck presenting as a soft-tissue
      tumour.
AB  - Myositis ossificans is usually the result of direct injury to a muscle and is a
      self-limiting disease. It may present as a soft-tissue mass with a broad
      differential diagnosis, including highly malignant tumours, such as soft-tissue
      sarcomas. Many theories can be found concerning the aetiology of myositis
      ossificans, but minor or major traumas are considered to be the most common
      cause. A unique case of myositis ossificans of the neck in a 17-year-old
      professional, female, ground gymnast, who presented initially with a soft-tissue
      tumour, was treated successfully. The main differential diagnosis is presented
      along with typical radiographic features on conventional radiography,
      computerised tomography and magnetic resonance imaging, and typical pathological
      appearance, such as the pathognomonic "zoning phenomenon". Myositis ossificans
      should be added to the differential diagnosis of every young patient who engages
      in sport presents with a soft-tissue mass. Careful padding of the area and
      teaching the rolling technique to avoid repeated injuries to the neck can prevent
      recurrence.

PMID- 11317690
TI  - Dorsal compression of the epidural cord due to free sequestral lumbar prolapse.
      Diagnostic problems in magnetic resonance imaging and computed tomography.
AB  - Due to the anatomical situation, intervertebral disc herniation usually results
      in compression of the anterior epidural space, with lateral or medial irritation
      of nerve root or cauda equina. Rare locations are an intra- or extraforaminal
      position or dislocation dorsally. Three patients with dorsal cauda equina
      compression caused by a sequestered herniated nucleus pulposus (HNP) are
      reported. The patients complained mainly of severe back pain. In two patients
      nondermatome-related leg pain was observed; one patient suffered additionally
      from incomplete cauda equina syndrome. In all cases magnetic resonance imaging
      and computed tomography diagnosed neoplastic tissue.

PMID- 11317691
TI  - Use of anti-tumour necrosis factor agents in inflammatory bowel disease. European
      guidelines for 2001-2003.
AB  - The introduction of novel anti-tumor necrosis factor (TNF) agents has not only
      led to impressive new therapeutic opportunities but also resulted in uncertainty
      regarding their optimal use and possible side effects. Guidelines are presented
      here for the use of anti-TNF agents in gastrointestinal disorders. Experts were
      chosen from different European countries by an algorithm to avoid bias. An expert
      consensus on guidelines was established using a two-stage procedure of systematic
      Medline and abstract search for evidence and a qualifying meeting to derive
      recommendations. Detailed guidelines were developed for the use and the future
      clinical development of anti-TNF agents in inflammatory bowel disease. Grading of
      available evidence and grading of recommendations were performed according to
      AHCPR guidelines. At present infliximab is the only registered agent for Crohn's
      disease. Infliximab should be always used at a dose of 5 mg/kg. The guidelines
      define the indications both in refractory and in fistulating disease for the
      readministration and before surgery. Guidelines for safety and for concomitant
      treatments are given. Prospects, potential clinical use, and future directions
      for the clinical development of other anti-TNF agents are detailed. Clinical use
      of anti-TNF agents will be influenced by a large number of clinical trials being
      concluded in 2001 and 2002. It is likely that anti-TNF therapies will become an
      important long-term therapy for a proportion of patients with Crohn's disease.
      Biological agents will be followed by smaller and more stable, orally available
      compounds. These guidelines will be succeeded by a formal public consensus in
      2002/2003.

PMID- 11317692
TI  - Dual effect of chronic nicotine administration: augmentation of jejunitis and
      amelioration of colitis induced by iodoacetamide in rats.
AB  - Smoking has a dichotomous effect on inflammatory bowel disease, ameliorating
      disease activity in ulcerative colitis but having a deleterious effect on Crohn's
      disease. This effect is thought to be due to nicotine. We investigated the effect
      of chronic nicotine administration on the small and large bowel in iodoacetamide
      induced jejunitis and colitis. Jejunitis was induced in Sprague-Dawley rats by
      intrajejunal administration of 0.1 ml 2% iodoacetamide and colitis by intrarectal
      administration of 0.1 ml 3% iodoacetamide. Nicotine was dissolved in drinking
      water (12.5 or 250 micrograms/ml), rats drinking ad libitum. Nicotine
      administration started 10 days prior to damage induction and throughout the
      experiment and had no effect on weight gain or daily food intake of rats. Rats
      were killed 5 days after iodoacetamide-induced colitis and 7 days after induction
      of jejunitis. The jejunum and colon were resected, rinsed, weighed, damage
      assessed macroscopically and microscopically and tissue processed for
      myeloperoxidase and nitric oxide synthase (NOS) activities and prostaglandin E2
      (PGE2) generation. Effects of nicotine on gut microcirculation were also
      assessed. Nicotine by itself caused no damage to the colon. Nicotine had a
      dichotomous effect on jejunitis and colitis. At a dose of 12.5 micrograms/ml
      nicotine improved the macroscopic damage of colitis from 252 +/- 66 to 70 +/- 31
      mm2, and segmental weight also declined significantly in the colon (from 1.7 +/-
      0.2 to 1.2 +/- 0.1 g/10 cm). In contrast, the same dose of nicotine had a
      deleterious effect on iodoacetamide-induced jejunitis, increasing the macroscopic
      damage from 368 +/- 38 to 460 +/- 97 mm2 in rats treated with injury escalating
      to 970 +/- 147 in rats treated with 250 micrograms/ml nicotine. Nicotine
      treatment also significantly increased jejunal segmental weight. By itself
      nicotine did not change NOS activity or PGE2 generation compared to control rats,
      but it enhanced microcirculation in the colon, whereas in the jejunum nicotine
      decreased PGE2 generation and increased NOS activity but not jejunal
      microcirculation. Nicotine has opposite effects on iodoacetamide-induced colitis
      and jejunitis, which may be partly explained by decreased PGE2 generation and
      increased NOS activity in the jejunum and an increase in the colonic
      microcirculation.

PMID- 11317693
TI  - p53 autoantibodies in sera of patients with a colorectal cancer and their
      association to p53 protein concentration and p53 immunohistochemistry in tumor
      tissue.
AB  - We evaluated p53 autoantibodies (p53-Ab) as a preoperative tumor marker and as a
      prognosis marker. We also investigated whether p53-Ab production is dependent on
      p53 protein overexpression in tumor tissue or on tumor volume. Serum samples of
      patients with a colorectal cancer (n = 130) and of healthy controls (n = 44) were
      examined for p53-Ab using an ELISA kit. P53 protein expression in tumor tissue
      was demonstrated immunohistochemically and quantified by ELISA. Tumor volume was
      calculated and patients' survival computed using the Kaplan-Meier method. p53-Ab
      were detected in the serum from 15% of patients; all controls were negative.
      There was a significant correlation between p53-Ab production and positive
      immunostaining or p53 protein concentration in tumor tissue. p53-Ab were detected
      at a higher percentage of patients with a tumor volume of 10 cm3 or greater than
      in those with a smaller tumor. No difference in patients' prognosis was found
      between the p53-Ab positive and negative groups. Because of their low sensitivity
      (15%) p53-Ab are not suitable as a preoperative tumor marker. However, their high
      specificity (100%) and their potential for early diagnosis of a tumor relapse
      makes them valuable for postoperative monitoring during follow-up in p53-Ab
      positive patients. Furthermore, their detection can be used as a simple
      serological test for early detection of p53 alterations.

PMID- 11317694
TI  - Costs and efficiency of a tumor follow-up program for the detection of colorectal
      liver metastases.
AB  - From January 1987 until July 1999 we admitted 1003 patients with colorectal
      cancer and 31 with resected colorectal liver metastases to our tumor follow-up
      program. After R0 resection of the primary tumor 60 patients developed liver
      metastases during the postoperative follow-up. R0 resection of the metastases was
      performed in 16 of these cases without lethality and low morbidity. In the
      further course of the follow-up 8 of these patients again developed liver
      metastases, two of whom underwent reoperation. The overall 5-year survival rate
      after R0 resection of liver metastases was 20%. In 726 patients we performed 3719
      follow-up examinations. Following the German regulations on physicians' fees for
      follow-up-examinations we calculated the cost of detecting a liver metastasis to
      be DM 16,500 per patient. Mean costs were DM 62,000 in patients in whom the
      metastases were successfully resected. The results of this study show that
      although the costs are very high for patients who benefit from the follow-up
      program, 26.7% of those with liver metastases are detected in such an early
      stage, and that an R0 resection can be performed. This study shows that the high
      costs of tumor follow-up programs for detecting liver metastases in patients with
      resected colorectal cancer can be justified by the good outcome of patients in
      whom an early diagnosis of recurrent disease is made.

PMID- 11317695
TI  - Colorectal carcinoma liver metastases: clinical significance of preoperative
      measurement of serum carcinoembryonic antigen and carbohydrate antigen 19-9
      levels.
AB  - The clinical significance of preoperative levels of serum carcinoembryonic
      antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9) was evaluated in patients
      with colorectal carcinoma liver metastases. Preoperative serum CEA and CA 19-9
      levels, the number and size of liver metastases, and survival data were analyzed
      retrospectively in 73 patients. Using the cutoff level of 5 ng/ml for CEA and 37
      U/ml for CA 19-9, the positivity of these for detecting metastatic deposits were
      81% and 56%, respectively. CEA level was correlated with the number (P = 0.0081)
      and size (P = 0.013) of liver metastases among patients with positive CEA level,
      while CA 19-9 level was correlated only with the number of liver metastases (P =
      0.0072) among those with positive CA 19-9 level. In the overall series,
      preoperative CEA and CA 19-9 levels were correlated significantly with survival
      only at higher cutoff levels. In 46 patients undergoing curative hepatectomy,
      however, these levels were not correlated with survival, even at higher cutoff
      levels. In conclusion, the CEA level is closely associated with the extent of
      liver metastases, while the CA 19-9 level may reflect multiplicity of hepatic
      deposits. Preoperative measurement of serum CEA and CA 19-9 levels appears to be
      of some prognostic value.

PMID- 11317696
TI  - Prognostic significance of recurrent chromosomal aberrations detected by
      comparative genomic hybridization in sporadic colorectal cancer.
AB  - Colorectal carcinomas are characterized by frequent recurrent gains and losses of
      chromosomal material, especially gains of chromosome arms 20q and 13q, and losses
      of chromosome arms 18q and 4q. These may be important in the development and
      progression of colorectal carcinomas. Chromosomal aberrations detected by
      comparative genomic hybridization in 67 sporadic colorectal carcinomas were
      examined for their possible associations with patient survival. Dukes' stage,
      tumor DNA ploidy status, and TP53 genotype/phenotype were also examined for the
      same. Patients with losses of chromosomal arms 1p, 4q, 8p, 14q, or 18q or gain of
      chromosomal arm 20q had significantly shorter survival times than those without
      these aberrations (univariate relative risk 3.45, 2.71, 3.32, 3.26, 3.32, 3.91,
      respectively), as did patients with more than six chromosomal aberrations per
      tumor than those with fewer than six aberrations (univariate relative risk 3.26,
      P = 0.013). DNA aneuploidy and Dukes' stage C + D resulted in poor patient
      survival (univariate relative risk 3.58, 3.39, respectively). Dukes' stage C + D,
      1p loss and 8p loss emerged as the only independent prognostic parameters
      (relative risk 3.22, 2.53, 2.45, respectively) when entered into multivariate
      survival analysis together with other significant parameters from univariate
      survival analysis. Loss of chromosome arm 1p, 4q, 8p, 14q, or 18q or gain of
      chromosome arm 20q thus results in shortened survival times in colorectal cancer
      patients. 1p loss and 8p loss were shown to be independent predictors of poor
      prognosis.

PMID- 11317697
TI  - Air insufflation: a useful adjunct to the single contrast barium enema for the
      evaluation of the rectum.
AB  - We examined whether insufflation of a small volume of air after a single-contrast
      barium enema would improve evaluation of the rectum. Eighty patients presenting
      for barium enema by single-contrast technique underwent examination of the colon
      including spot films with fluoroscopy and palpation during introduction of the
      barium and filled overhead views, using standard apparatus and technique. The
      examination was completed by draining barium from the rectum only, following
      which air in the barium enema bag was squeezed back into the rectum and three
      views of the rectum obtained (lateral, left posterior oblique, and frontal). Two
      reviewers then chose the best image of the rectum from each study with relevance
      to luminal distention and visibility of surface detail of the rectum. Following
      air insufflation, improved surface detail visualization was recognized by both
      reviewers in 69 (86%) patients and by one reviewer in 10 (12%) patients, a
      statistically significant observation (P < 0.0001). There was a trend towards
      improved rectal distention, recognized by both reviewers in 37 (46%) patients and
      by one reviewer in 18 cases (22%). In 25 (31%) patients neither reviewer
      recognized any improvement in rectal distention. Rectal abnormalities were
      identified in nine cases; there were two large carcinomas, two radiation
      strictures, two rectal fistulae, two small rectal polyps (5 and 7 mm), and one
      case of prolapsing rectal mucosa. All rectal abnormalities were visible on the
      air insufflation views. In the two cases of suspected rectal polyp and one of the
      cases of rectal fistula, the findings were not visible on the initial barium
      filled views. A normal rectum was observed in 71 cases. Follow-up of these 71
      patients found no later evidence of any rectal abnormalities. Improved filling of
      the proximal colon following air insufflation was observed in 12 (15%) patients,
      an additional and unexpected benefit of this maneuver. Air insufflation is a
      simple addition to the SCBE study that improves visualization of the rectum.

PMID- 11317698
TI  - Contribution of posture to the maintenance of anal continence.
AB  - The anorectal angle (ARA) is believed to provide one of the most important
      contributions to anal continence. The normal resting angle is approx. 90 degrees,
      but the erect position may modify the ARA and other parameters usually considered
      in a proctometrogram. We compared the proctometrogram in different postures to
      elucidate the role of changes in the ARA in maintaining fecal continence. Sixty
      three patients with constipation underwent static proctography. Variations in the
      ARA, perineal descent, puborectalis muscle length, and pubococcygeal distance
      were determined during resting, squeezing, and pushing with the patient in the
      Sims' position (SP); further evaluations used radiographs in resting position but
      with straight legs, in erect and sitting positions. The resting mean ARA was 95.3
      +/- 15 degrees in SP and 79.8 +/- 14 degrees standing erect; the latter value was
      also significantly less during squeezing (84 +/- 11 degrees). The mean ARA during
      pushing was 118 +/- 16 degrees. A systematic and statistically significant
      difference in the mean resting ARA was demonstrated using the baseline of the
      rectal shape instead of the major rectal axis when measuring the anorectal angle.
      When sitting on a toilet, the mean resting ARA was significantly wider than in
      SP. The length of the puborectalis sling at rest did not change but was
      significantly reduced during squeezing and increased during pushing. The descent
      of the perineum at rest was near to 0 (-0.089 +/- 1.76 cm) in SP and
      significantly less when standing (-0.65 +/- 1.9 cm) and during squeezing (-0.97
      +/- 1.7 cm). Perineal descent during pushing was +2.94 +/- 2.2 cm. The mean
      pubococcygeal distance did not change significantly in SP and in the erect
      position. The erect position thus contributes significantly to the maintenance of
      fecal continence by sharpening the ARA. This effect is stronger than any active
      contraction of the puborectalis muscle and is not related to shortening of the
      puborectalis sling but is secondary to lifting of the pelvic floor.

PMID- 11317699
TI  - Nonocclusive ischemic colitis in a 12-year-old girl: value of unenhanced spiral
      computed tomography.
AB  - A 12-year-old girl was hit by a car and arrived in the emergency room in
      hemorrhagic shock. Contrast-enhanced computed tomography of the abdomen showed
      traumatic rupture of the liver and large amounts of intraperitoneal hemorrhage.
      Unenhanced computed tomography showed a hyperdense thickening of the wall of the
      descending colon. This finding was consistent with a nonocclusive ischemic
      colitis, which was confirmed some days later by endoscopy, at a time when the
      patient had already developed Gram-negative bacteremia. We discuss the
      pathogenesis of nonocclusive ischemic colitis, computed tomography findings, and
      the value of unenhanced computed tomography.

PMID- 11317700
TI  - Shock-associated nonocclusive ischemic colitis: a very rare event in young
      patients after trauma.

PMID- 11317701
TI  - Incarcerated and strangulated rectal prolapse.

PMID- 11317702
TI  - Study on the cytochrome P-450- and glutathione-dependent biotransformation of
      trichloroethylene in humans.
AB  - OBJECTIVES: To investigate in humans the contribution of the cytochrome P-450-
      and glutathione-dependent biotransformation of trichloroethylene (TRI) under
      controlled repeated exposure in volunteers, and under occupational conditions.
      METHODS: Volunteers were exposed to TRI, using repeated 15 min exposures at 50
      and 100 ppm. This exposure schedule resulted in internal doses of 1.30 and 2.40
      mmol of TRI respectively. Urine samples were collected for a minimum of 45 h.
      Urine samples were also collected from occupationally exposed workers. The
      samples were analysed for the known human metabolites of TRI, trichloroethanol
      (TCE), trichloroacetic acid (TCA) and both regio-isomeric forms of the
      mercapturic acid N-acetyl-S-(dichlorovinyl)-L-cysteine (DCV-NAC), and for
      (dichlorovinyl)-L-cysteine (DCVC). In order to further elucidate the metabolism
      of TRI in humans, we analysed samples for dichloroacetic acid and for the
      proposed break-down products of 1,2 and 2,2-dichlorovinyl-L-cysteine after
      deamination: the S-conjugates of 3-mercaptolactic acid, 3-mercaptopyruvic acid
      and 2-mercaptoacetic acid. RESULTS: None of the glutathione metabolites was found
      in urine of volunteers. In workers occupationally exposed to TRI at levels
      between 0.4 and 21 ppm [8-h time-weighted average (TWA)], levels of DCV-NAC in
      urine samples collected at the end of the 4th working day and also next morning
      were below detection limit (0.04 mumol/l). This confirms the findings of Bernauer
      et al. (1996) that these metabolites are excreted at very low levels in humans.
      Urinary levels of DCVC and six postulated metabolites of dichlorovinyl-S-cysteine
      conjugates via deamination were also below 0.04 mumol/l, indicating that at most
      0.05% of the dose is excreted in the form of these metabolites. These data
      further strengthen the argument for a very low activity of glutathione-mediated
      metabolism for chronically exposed workers. CONCLUSIONS: This study gives
      additional data which indicate that glutathione-mediated metabolism is of minor
      importance in humans exposed to TRI. In spite of indications to the contrary,
      significant metabolism of the cysteine conjugate via beta-lyase, which could
      result in a toxic metabolite, cannot be ruled out completely.

PMID- 11317703
TI  - Carcinogenicity assays of wood dust and wood additives in rats exposed by long
      term inhalation.
AB  - OBJECTIVE: This study evaluates whether wood dust and/or wood preservatives
      develop a carcinogenic potential against the tissues of the airways of rats.
      METHODS: The formation of tumors of the respiratory tract after exposure to wood
      dust was studied in six groups of approximately 60 female Fischer 344 rats
      exposed by long-term inhalation to mean concentrations of (1) 18 mg/m3 of
      untreated oak wood dust, (2) wood preservatives containing ca. 1 microgram/m3
      lindane and 0.2 microgram/m3 of pentachlorophenol (PCP) in the exposure air, or
      lindane and 18 micrograms/m3 of PCP (group lindane/PCP vapors, and group oak wood
      treated with lindane/PCP), (3) 21 or 39 micrograms/m3 of sodium dichromate
      (calculated as CrO3, group chromate aerosol and group oak wood with chromate),
      and 72 micrograms/m3 of N-nitrosodimethylamine vapors as positive control. The
      negative control group consisted of 115 animals (sham-exposed). RESULTS: Tumors
      of the nasal cavity developed in two rats exposed to chromate aerosol or in
      combination with wood dust (2/102, 2%). Malignant tumors of the lower respiratory
      tract were induced only in exposed groups of rats (three adenocarcinomas of the
      lung and four bronchiolar lung carcinomas, 7/254, 2.8%). More respiratory tract
      tumors were observed in rats exposed to chromate or wood with chromate (5/102,
      5%), also in groups exposed to oak wood dust (oak untreated, oak + chromate, oak
      + lindane/PCP; together 5/155, 3.2%). Analysis of 'unpreserved' oak wood dust
      revealed up to 5 micrograms/m3 of chromate. When this exposure was taken into
      account, eight of nine animals with respiratory tract tumors (including nasal
      cavity) had exposure to chromate, while only one tumor occurred in the group
      lindane/PCP. Otherwise the incidence of systemic tumors was increased in animals
      exposed to lindane/PCP, due in particular to a significantly increased incidence
      of liver tumors (OR = 3.7; 1.24-11.3; P = 0.019). Fatal (mucoepidermoid) tumors
      were induced by N-nitrosodimethylamine (NDMA) in the positive control (14/46,
      30%). No such tumors of the respiratory tract were observed in the negative
      control. CONCLUSIONS: Tumors in the respiratory tract were found only in exposed
      animals, predominantly in the groups which inhaled oak wood dust and chromate
      stain. Chromate may play a decisive role for the etiology of tumors of the nasal
      cavity in wood workers. This assumption should be supported by further dose
      response studies.

PMID- 11317704
TI  - Cardiac output changes during hyperbaric hyperoxia.
AB  - OBJECTIVES: Increased ambient pressure and oxygen partial pressure (pO2)
      influence cardiovascular regulation during diving and caisson work. We measured
      the cardiac output (Q) in subjects who practiced moderate work at a usual diving
      depth of 30 m. METHODS: In 23 healthy male Navy divers who performed steady state
      bicycle exercises (100 W workload) in a hyperbaric chamber Q was measured by a
      CO2-rebreathing technique at normal pressure (100 kPa) and at raised ambient
      pressure (400 kPa), in a random order. During the rebreathing maneuver the
      subjects were exposed to pO2 values which theoretically may have reached a
      maximum value of 87 kPa (normobaric) and 388 kPa (hyperbaric). During the
      experiments the ambient temperature ranged between 22 and 25 degrees C. RESULTS:
      There was a significant decrease of the directly measured Q, heart rate (HR) and
      the calculated stroke volume at depth when compared with normoxic and normobaric
      exercise. The decrease of Q amounted to 64% of the normobaric value (8.9 l min-1
      versus 13.9 l min-1). The mean HR decreased from 104.7 min-1 (100 kPa) to 94.0
      min-1 (400 kPa). The calculated mean stroke volume decreased from 133 ml (100
      kPa) to 96 ml (400 kPa). CONCLUSIONS: During hyperoxic hyperbaria the peripheral
      vascular tonus increases due to the consecutively increased arterial oxygen
      content. The cardiac output may correlate to the peripheral vasoconstriction and
      is therefore indirectly influenced by elevation of inspiratory pO2 i.e. during
      the rebreathing maneuver.

PMID- 11317705
TI  - Ocular discomfort and conjunctival alterations in operating room workers. A
      single-institution pilot study.
AB  - OBJECTIVES: The aim of this pilot study was to relate the eye symptoms complained
      of by subjects working in the operating rooms of a hospital in southern Italy,
      with the observations of alterations of the ocular surface. METHODS: An
      epidemiological study was carried out by a questionnaire aimed at investigating
      the prevalence of ocular discomfort symptoms among 213 subjects working in
      operating rooms and 40 subjects working in the wards. The investigated symptoms
      were the following: tiredness, heaviness, burning, redness, tearing, itching,
      blinking, foreign body sensation, and photophobia. A randomised comparative study
      of the ocular surface and conjunctival cytology was also carried out, comparing
      two groups of age- and gender-matched subjects. Group 1 included 24 subjects
      randomly chosen from the operating room workers with ocular discomfort symptoms;
      group 2 included ten subjects randomly enrolled from hospital personnel working
      in the wards. Ophthalmological examination of the ocular surface was performed on
      each subject in the following order: slit-lamp examination, break-up time (BUT)
      of the pre-corneal tear film, corneal fluorescein stain, lachrymal basal
      secretion test, conjunctival impression cytology. RESULTS: A high prevalence
      (72.3%) of ocular discomfort symptoms was reported by operating room workers,
      while in ward personnel the prevalence was 55% (P = 0.04). The ocular tests
      showed that the conjunctival features and BUT were statistically significantly
      altered in subjects in group 1. Also, the conjunctival impression cytology study
      showed statistically significant alterations of all the investigated parameters:
      specimen cellularity, cell-to-cell contacts, nucleus/cytoplasm ratio, chromatin
      pattern, goblet cell distribution, keratinisation and the total cytological
      score. CONCLUSIONS: Our results show that self-reported eye complaints and ocular
      surface alterations have a high prevalence in subjects working in the operating
      rooms. This seems to indicate that the operating room environment could play a
      role in the onset of the eye disturbances.

PMID- 11317706
TI  - Nasal symptoms among workers exposed to soft paper dust.
AB  - OBJECTIVES: To clarify whether occupational exposure to paper-dust is associated
      with an increased risk of non-infectious rhinitis. METHODS: Thirty-seven workers
      exposed to paper-dust in a soft-paper mill were compared with 36 unexposed
      controls. The study was performed under normal working conditions during the non
      pollen season. Medical and occupational history was taken down in a comprehensive
      questionnaire and nasal symptoms were scored on a visual analogue scale (VAS).
      Pulmonary and nasal function was assessed by spirometry, acoustic rhinometry and
      peak nasal inspiratory flow. Nasal lavage was analysed for interleukin-8 (IL-8)
      and nasal transit time was monitored with the saccharine test. Concentrations of
      inhalable dust for each exposed subject during the day of the clinical study were
      measured with personal sampling devices. RESULTS: There was an increased
      prevalence of nasal blockage and crust formation among the exposed workers.
      However, there was no difference with regard to acoustic rhinometry, nasal
      transit time or nasal peak inspiratory flow. In the whole population, IL-8 in
      nasal lavage was higher among men than among women, 193 ng/l vs 132 ng/l, P =
      0.006. There was also a positive trend (P = 0.01) with increasing nasal IL-8
      going from non-smokers (122 ng/l), ex-smokers (126 ng/l) to current smokers (235
      ng/l). CONCLUSIONS: We have found that occupational exposure to paper-dust is
      associated with symptoms of nasal blockage and nasal crusting. We find no
      objective signs of nasal inflammation, even among the subgroup with the highest
      current exposure.

PMID- 11317707
TI  - Inorganic fibres in the lung tissue of Hungarian and German lung cancer patients.
AB  - OBJECTIVE: To ascertain the lung burden of asbestos fibres in Hungarian lung
      cancer patients in comparison with the cumulative asbestos exposure estimated
      from the occupational history. METHODS: For 25 Hungarian lung cancer patients,
      lung tissue fibre analysis was performed by scanning transmission electron
      microscopy (STEM) and counting of ferruginous bodies (FBs) by light microscopy.
      Cumulative asbestos exposure in fibre-years was assessed from a standardised
      occupational history using the report "fibre years" of the German
      Berufsgenossenschaften. RESULTS: Median and maximum concentrations of fibres
      longer 5 microns per gram dry lung tissue (g dry) were 0.03 and 7.38 million
      fibres/g dry for chrysotile, 0.00 and 0.21 million fibres/g dry for amphibole and
      0.22 and 0.62 million fibres/g dry for other mineral fibres (OMFs). The maximum
      values were observed in one patient for whom a high asbestos exposure was evident
      in advance from the occupational history. CONCLUSIONS: In comparison with
      reference values obtained by the same method for German patients with no
      indication of workplace asbestos exposure, increased concentrations of more than
      0.2 million chrysotile fibres/g dry were obtained for six of the 25 Hungarian
      patients (24%). For one of them, the second highest estimate of a workplace
      exposure of 60 fibre-years and the highest tissue concentration of 7.38 million
      chrysotile fibres/g dry substantiate a high probability of a causal relationship
      to asbestos. A further comparison can be made with the results for 66 German
      patients treated by surgical lung resection for a disorder other than
      mesothelioma, mainly lung cancer. For the Hungarian lung cancer patients, similar
      amounts of chrysotile but distinctly lower amounts of amphibole fibres and
      distinctly higher amounts of OMFs were observed. A correlation between exposure
      estimates from occupational history and concentration of fibres in the lung
      tissue was observed for amphibole (Spearman: R = 0.66, P < 0.001, Pearson: R =
      0.50, P = 0.01) and for chrysotile (Pearson: R = 0.48, P = 0.02).

PMID- 11317708
TI  - Further round-robin tests to improve the comparability between laboratories of
      the measurement of carbon in diesel soot and in environmental samples.
AB  - OBJECTIVES: An informal European coordination group organized two round-robin
      tests on filters collected from environmental, workplace and diluted diesel
      emissions. Previous inter-laboratory comparisons have shown that experimental
      samples give reasonably good results in terms of the dispersion around the mean,
      from all the participating laboratories. However, there were significant
      differences between the laboratories owing to a narrow distribution of the
      results within a single laboratory. In order to gain a better understanding of
      the differences obtained between the laboratories, it was decided to carry out
      more round-robin tests and to investigate further the possible factors which may
      influence the results. METHODS: The first round-robin (RRT3) was performed on six
      different samples (eight replicates) analyzed by ten laboratories. The range of
      loading was 40 to 138 micrograms cm-2 of total carbon (TC). Laboratories used
      their own thermal procedure parameters. The second round-robin test (RRT4) was
      performed on three different diluted diesel emissions (two replicates) samples
      analyzed by 13 laboratories. The range of loading was 21 to 37 micrograms cm-2
      TC. Laboratories analyzed samples using imposed temperatures (500, 650 and 800
      degrees C) and imposed duration (12 min). RESULTS: Inter-laboratory coefficients
      of variation for diluted diesel emission samples were 10% for RRT3 and ranged
      from 6 to 19% for RRT4. The influence of the desorption temperature was clearly
      demonstrated and the results tended to show that a desorption temperature of 650
      degrees C could be an acceptable compromise. The influence of the organic
      carbon/elemental carbon (OC/EC) ratio was shown to be insignificant with pure
      diesel soot samples. CONCLUSIONS: It was expected that a significant improvement
      would be seen in the inter-laboratory dispersion by the use of a common
      standardized thermal desorption program, but the objectives of these RRTs were
      only partly reached. This paper provides new information that will be useful in
      the elaboration of a standardized procedure for the European Normalisation Centre
      (CEN TC 137 WG2--General requirements for measuring procedures).

PMID- 11317709
TI  - Use of solvents in industries in Korea: experience in Sinpyeong-Jangrim
      industrial complex.
AB  - OBJECTIVES: To identify the most popular solvent and typical type of solvent work
      among solvent-using workplaces in Korea. METHODS: In practice, 862 solvent-using
      workshops in Sinpyeong-Jangrim industrial complex in Pusan were investigated in a
      2-year period from March 1995 to February 1997. Solvent vapors in the breathing
      zone of workers were collected by personal sampling with charcoal tubes. The
      exposed charcoal was extracted with carbon disulfide, and the solvents in the
      extract were analyzed by flame ionization detector-equipped gas chromatography
      (FID-GC). RESULTS: Solvents were used in painting, glue application, cleaning,
      printing and solvent-mixing workshops in decreasing order of popularity. Toluene
      was the most frequently measured solvent. In the five types of solvent work,
      acetone, hexane, methyl ethyl ketone, methyl isobutyl ketone,
      tetrachloroethylene, trichloroethylene and xylenes were also used frequently.
      CONCLUSIONS: Toluene was identified as the most frequently used solvent in
      solvent works in Korean manufacture industries in the late 1990s. Eight types of
      solvent were popularly used in five popular types of solvent work. These trends
      are very similar to the cases reported for industries in Japan.

PMID- 11317710
TI  - Relationships between perceived workload, stress and oxidative DNA damage.
AB  - OBJECTIVES: The present study was performed to investigate the relationship
      between work-related factors, including psychological stress, and the formation
      of a type of oxidative DNA damage, 8-hydroxydeoxyguanosine (8-OH-dG), in order to
      examine their possible risk factor for occupational carcinogenesis. METHODS: A
      total of 54 healthy workers (27 male and 27 female, aged 41.2 +/- 12.5 years) in
      a company were investigated for 8-OH-dG levels in the peripheral blood leukocytes
      at the time of a questionnaire survey regarding several factors, such as working
      hours, workload, fatigue, sleep, psychological stress and the prospect of
      alleviating it. Subjects were limited to non-smoking and non-drinking workers to
      exclude the influence of cigarette smoking and alcohol drinking, which have been
      reported to have associations with the formation of 8-OH-dG. RESULTS: The levels
      of 8-OH-dG in female subjects were significantly related to the perceived
      workload (F = 5.56, P = 0.010), the perceived psychological stress (F = 6.15, P =
      0.007), and the impossibility of alleviating stress (F = 3.82, P = 0.048). No
      associations were observed in male subjects. CONCLUSIONS: Psychological stress
      and perceived over-work appear to be related to the pathogenesis of cancer via
      the formation of 8-OH-dG, particularly in female workers.

PMID- 11317711
TI  - Review of the factors associated with musculoskeletal problems in epidemiological
      studies.
AB  - OBJECTIVES: To review systematically all epidemiological studies of the past 15
      years concerning the factors associated with musculoskeletal disorders (MSDs) or
      complaints of the neck and upper limbs. METHODS: Fifty-seven cross-sectional and
      seven longitudinal studies were reviewed. A list was made of all personal,
      occupational, extra-occupational and psycho-organisational factors taken into
      consideration in each study, and of those that were found in association with
      MSDs. MSDs of the neck-shoulder region (NSs) and hand-wrist (HWs) were considered
      separately. About 70 different factors are listed. RESULTS: This inventory
      identifies the factors or categories of factors that were generally taken into
      consideration. It makes it possible also to evaluate the strength of the
      association with a given factor, in considering the number of studies finding an
      association, and those that did not consider this factor. Based on this review,
      some factors taken into consideration (such as weight or hobbies) could be
      excluded in further studies, and replaced by more specific psycho-organisational
      factors.

PMID- 11317712
TI  - Internal exposure to PAHs of children and adults living in homes with parquet
      flooring containing high levels of PAHs in the parquet glue.
AB  - PAHs form during the incomplete combustion of organic substances and hence they
      are distributed ubiquitously in the environment. PAHs in the diet are the main
      source of exposure in man. In 1997 a new source of potential PAH exposure was
      discovered: very high levels of polycyclic aromatic hydrocarbons (PAHs) and benzo
      a-pyrene (BaP) were detected in household dust from former American Forces
      housing in Frankfurt am Main, Germany, built in 1955/1956. This contamination was
      caused by a parquet glue containing coal tar, the use of which was formerly
      standard building practice in Germany. Because the inhabitants of these flats
      were very concerned about the effects on their health, they were offered the
      opportunity to take part in biomonitoring examinations to assess individual
      internal PAH exposure. PARTICIPANTS AND METHODS: 1213 inhabitants from 511
      flats/houses took part in the investigation; this corresponds to 12.7% of the
      total inhabitants of the former US housing estates in Frankfurt am Main. Spot
      urine samples were collected and frozen until analysis for 1-, 2-, 3- and 4
      hydroxyphenanthrene and 1-hydroxypyrene, which was carried out using a very
      sensitive and practical high performance liquid chromatographic method with
      fluorescence detection, approved by the Deutsche Forschungsgemeinschaft. RESULTS:
      The level of internal exposure to PAHs in study participants living in homes
      where parquet glue containing PAHs had been used did not differ from the levels
      found in participants in whose homes PAH-containing parquet glue was not used.
      This was true for the whole group as well as subgroups divided according to age
      and smoking behaviour. Internal exposure was not influenced by different levels
      of external exposure (BaP in parquet glue and in household dust). Spearman rank
      correlations between the level of BaP in parquet glue and in household dust were
      low and insignificant. CONCLUSION: An increase in internal PAH exposure due to
      high levels of PAHs in parquet glue and household dust could not be detected.
      This confirms earlier results with small collectives, where only low and
      insignificant trends were found towards higher internal PAH exposure caused by
      contaminated homes. Therefore, the ad-hoc working group of the Commission for
      Indoor Air Quality of the German Federal Environmental Agency stated that a
      definitive threshold limit value cannot be defined for PAH contamination in
      parquet glue and household dust. For reasons of disease prevention, however, BaP
      contamination in household dust exceeding 10 mg/kg should be minimised.

PMID- 11317713
TI  - Evaluatiing long-term outcomes of treatments for drug and alcohol addiction.
      Introduction.

PMID- 11317714
TI  - A review of temporal effects and outcome predictors in substance abuse treatment
      studies with long-term follow-ups. Preliminary results and methodological issues.
AB  - This article is an initial report from a review of alcohol and drug treatment
      studies with follow-ups of 2 years or more. The goals of the review are to
      examine the stability of substance use outcomes and the factors that moderate or
      mediate these outcomes. Results from 12 studies that generated multiple research
      reports are presented, and methodological problems encountered in the review are
      discussed. Substance use outcomes at the group level were generally stable,
      although moderate within-subject variation in substance use status over time was
      observed. Of factors assessed at baseline, psychiatric severity was a significant
      predictor of outcome in the highest percentage of reports, although the nature of
      the relationship varied. Stronger motivation and coping at baseline also
      consistently predicted better drinking outcomes. Better progress while in
      treatment, and the performance of pro-recovery behaviors and low problem severity
      in associated areas following treatment, consistently predicted better substance
      use outcomes.

PMID- 11317715
TI  - State-level treatment outcome studies using administrative databases.
AB  - State substance dependence administrative databases contain both administrative
      and clinical information on large numbers of patients collected over extended
      time periods. Access to other state databases--employment, criminal behavior, and
      Medicaid--has also been achieved in some instances. Such data could prove an
      important source for the evaluation of long-term treatment outcomes and their
      determinants. This selected review describes and evaluates the treatment outcome
      and cost-related findings of the most advanced studies using these databases. A
      number of these studies have shown that completion of substance dependence
      treatment is associated with reduced societal costs. Some of these studies have
      focused on significant subpopulations of patients, including pregnant women and
      adolescents. A shortcoming of the findings of most of these studies concerns
      their use of noncompleter or non-randomly collected comparison groups. The
      utility of these databases can be enhanced by coupling them with clinical
      research treatment outcome evaluation approaches.

PMID- 11317716
TI  - The validity of self-reported cost events by substance abusers. Limits,
      liabilities, and future directions.
AB  - The following review considers data on the validity of self-reports in addict
      populations, and then it discusses (a) the types of cost-related questions and
      the assumptions underlying them that are useful to the evaluation of addictions
      treatment, (b) both internal and external sources of invalidity, (c) the limits
      on cost-related information that is gathered from administrative databases, (d)
      methods for assessing measure validity, and (e) the means for improving the
      validity of self-reports of cost events. With some important exceptions, addicts
      provide valid data about both medical and criminal cost events. Skilled
      socioeconomic researchers able to monetarize these events should be able to
      produce significant cost of illness, cost offset, cost-benefit, and cost
      effectiveness research using self-report data.

PMID- 11317717
TI  - Effectiveness of continuing care interventions for substance abusers.
      Implications for the study of long-term treatment effects.
AB  - Substance-abusing patients are frequently urged to participate in lower intensity
      continuing care interventions, also known as "stepdown care" or "aftercare,"
      following an initial phase of treatment. Since 1988, 15 controlled studies of
      continuing care for alcohol or drug abuse have been published, with follow-up
      data on substance use presented in 14 of these studies. In the studies that
      featured an active control condition, only 1 of 7 yielded positive findings. In
      the studies that featured a minimal- or no-treatment control, 3 of 7 studies
      yielded positive findings. The relative paucity of continuing care studies,
      coupled with the lack of stronger evidence of clinical effectiveness, provides a
      convincing rationale for conducting evaluations of continuing interventions, as
      well as evaluations of combinations of various primary and continuing
      interventions. Methodological issues in the evaluation of continuing care and
      potential research questions that could be addressed in long-term follow-up
      studies are outlined and discussed.

PMID- 11317718
TI  - Analytic approaches for assessing long-term treatment effects. Examples of
      empirical applications and findings.
AB  - Analytic approaches, including the structural equation model (autoregressive
      panel model), hierarchical linear model, latent growth curve model,
      survival/event history analysis, latent transition model, and time-series
      analysis (interrupted time series, multivariate time-series analysis) are
      discussed for their applicability to data of different structures and their
      utility in evaluating temporal effects of treatment. Methods are illustrated by
      presenting applications of the various approaches in previous studies examining
      temporal patterns of treatment effects. Recent advancements in these longitudinal
      modeling approaches and the accompanying computer software development offer
      tremendous flexibility in examining long-term treatment effects through
      longitudinal data with varying numbers and intervals of assessment and types of
      measures. A multimethod assessment will contribute to a more complete
      understanding of the complex phenomena of the long-term courses of substance use
      and its treatment.

PMID- 11317719
TI  - Clinical fluoroscopic fiducial-based registration of the vertebral body in spinal
      neuronavigation.
AB  - We present a system involving a computer-instrumented fluoroscope for the purpose
      of 3D navigation and guidance using pre-operative diagnostic scans as a
      reference. The goal of the project is to devise a computer-assisted tool that
      will improve the accuracy, reduce risk, minimize the invasiveness, and shorten
      the time it takes to perform a variety of neurosurgical and orthopedic procedures
      of the spine. For this purpose we propose an apparatus that will track surgical
      tools and localize them with respect to the patient's 3D anatomy and pre
      operative 3D diagnostic scans using intraoperative fluoroscopy for in situ
      registration and embedded fiducials. Preliminary studies have found a fiducial
      registration error (FRE) of 1.41 mm and a Target Localization Error (TLE) of 0.48
      mm. The resulting system leverages equipment already commonly available in the
      operating room (OR), providing an important new functionality that is free of
      many current limitations, while keeping costs contained.

PMID- 11317720
TI  - Statistical analysis of the morphology of three-dimensional objects and
      pathologic structures using spherical harmonics.
AB  - To support diagnosis and therapy, it is a fundamental aim of medical image
      processing to describe morphological characteristics of pathological structures
      or image objects in general. Different authors propose quantitative methods of
      description like bounding boxes[1], fourier descriptors[2] or contour moments[3].
      Unfortunately, these methods either don't supply a complete, respectively precise
      description of the object or only operate on two-dimensional images. Among the
      range of application are systems to classify lung nodules [4] or to help the
      diagnosis of brain tumors [5]. In this paper we present a method to analyze the
      morphology or shape of any three-dimensional object in order to describe it
      mathematically well-defined. We show how the description can be used to perform
      statistical operations on morphologies. The method presented in this paper was
      developed to assist the planning of craniofacial surgery. We analyze the shape of
      a given set of skull CT-data and use the mathematical description to
      statistically calculate the average shape of the skulls.

PMID- 11317721
TI  - Modeling and simulation for space medicine operations: preliminary requirements
      considered.
AB  - The NASA Space Medicine program is now developing plans for more extensive use of
      high-fidelity medical simulation systems. The use of simulation is seen as means
      to more effectively use the limited time available for astronaut medical
      training. Training systems should be adaptable for use in a variety of training
      environments, including classrooms or laboratories, space vehicle mockups, analog
      environments, and in microgravity. Modeling and simulation can also provide the
      space medicine development program a mechanism for evaluation of other medical
      technologies under operationally realistic conditions. Systems and procedures
      need preflight verification with ground-based testing. Traditionally, component
      testing has been accomplished, but practical means for "human in the loop"
      verification of patient care systems have been lacking. Medical modeling and
      simulation technology offer potential means to accomplish such validation work.
      Initial considerations in the development of functional requirements and design
      standards for simulation systems for space medicine are discussed.

PMID- 11317722
TI  - A comparative statistical analysis of neuronavigation systems in a clinical
      setting.
AB  - The use of neuronavigation (NN) in neurosurgery has become ubiquitous. A growing
      number of neurosurgeons are utilizing NN for a wide variety of purposes,
      including optimizing the surgical approach (macrosurgery) and locating small
      areas of interest (microsurgery). The goal of our team is to apply rapid advances
      in hardware and software technology to the field of NN, challenging and
      ultimately updating current NN assumptions. To identify possible areas in which
      new technology may improve the surgical applications of NN, we have assessed the
      accuracy of neuronavigational measurements in the Radionics and BrainLab systems.
      Using a phantom skull, we measured how accurate the visualization of a
      navigational probe's tip was in these systems, taking a total of 2180
      measurements. We found that, despite current NN tenets, error is maximal at the
      six marker count and minimal in the spreaded marker setting; that is, placing
      less markers around the area of interest maximizes accuracy and active tracking
      does not necessarily increase accuracy. Comparing the two systems, we also found
      that accuracy of NN machines differs both overall and in different axes. As
      researchers continue to apply technological advances to the NN field, an
      increasing number of currently held tenets will be revised, making NN an even
      more useful tool in neurosurgery.

PMID- 11317723
TI  - A meshless numerical technique for physically based real time medical
      simulations.
AB  - This work introduces, for the first time, a meshless modeling technique, the
      method of finite spheres, for physically based, real time rendering of soft
      tissues in medical simulations. The technique is conceptually similar to the
      traditional finite element techniques. However, while the finite element
      techniques requires a slow mesh generation process, this new technique has
      significant potential for multimodal medical simulations of the future since it
      does not use a mesh. Several examples are presented showing the effectiveness of
      the scheme.

PMID- 11317724
TI  - Manipulation of volumetric patient data in a distributed virtual reality
      environment.
AB  - Due to increases in network speed and bandwidth, distributed exploration of
      medical data in immersive Virtual Reality (VR) environments is becoming
      increasingly feasible. The volumetric display of radiological data in such
      environments presents a unique set of challenges. The shear size and complexity
      of the datasets involved not only make them difficult to transmit to remote
      sites, but these datasets also require extensive user interaction in order to
      make them understandable to the investigator and manageable to the rendering
      hardware. A sophisticated VR user interface is required in order for the
      clinician to focus on the aspects of the data that will provide educational
      and/or diagnostic insight. We will describe a software system of data
      acquisition, data display, Tele-Immersion, and data manipulation that supports
      interactive, collaborative investigation of large radiological datasets. The
      hardware required in this strategy is still at the high-end of the graphics
      workstation market. Future software ports to Linux and NT, along with the rapid
      development of PC graphics cards, open the possibility for later work with Linux
      or NT PCs and PC clusters.

PMID- 11317725
TI  - Bimanual haptic workstation for laparoscopic surgery simulation.
AB  - Realistic laparoscopic surgical simulators will require real-time graphic imaging
      and tactile feedback. Our research objective is to develop a cost-effective
      haptic workstation for the simulation of laparoscopic procedures for training and
      treatment planning. The physical station consists of a custom-built frame into
      which laparoscopic trocars and surgical tools may be attached/inserted and which
      are continuously adjustable to various positions and orientations to simulate
      multiple laparoscopic surgical approaches. Instruments inserted through the
      trocars are attached to end effectors of two haptic devices and interfaced to a
      high speed PC with fast graphics capability. The haptic device transduces 3D
      motion of the two manually operated surgical instruments into slave maneuvers in
      virtual space. The slave instrument tips probe the simulated organ. Simulations
      currently in progress include: 1) Surface-only renderings, deformation, and
      haptic interactions with elements in the gall gladder surgical field; 2) Voxel
      based simulations of the bulk manipulation of tissue; 3) laparoscopic
      herniorrhaphy. This system provides force feed-forward from the grasped tools to
      the contact tissue in virtual space, with deformation of the tissue by the
      virtual probe, and force feedback from the deformed tissue to the operator's
      hands.

PMID- 11317726
TI  - Cubby: a unified interaction space for precision manipulation.
AB  - Precision manipulation in surgical simulation poses special requirements on a VR
      system. One such requirement is unification, i.e. that the user manipulates a
      virtual object where it appears. We have designed Cubby, a system of which the
      visualization part was presented at MMVR97 [3], for precision manipulation and
      unification. In an experiment Cubby was compared with a single screen head
      tracked display, both in a unified and a non-unified version. The results show
      that subjects could manipulate virtual objects in Cubby with significantly higher
      accuracy and preferred it to the single screen head-tracked display. Though no
      significant difference in accuracy between the unified and non-unified conditions
      could be shown, subjects did prefer the unified over the non-unified condition
      within both setups.

PMID- 11317727
TI  - A methodological tool for computer-assisted surgery interface design: its
      application to computer-assisted pericardial puncture.
AB  - Computer Assisted Surgery systems are becoming more and more prevalent. Design
      processes currently used, pay only a small attention to the surgeon's
      interaction. To address this lack in design, we propose the OP-a-S notation: OP-a
      S modeling of a system adopts an interaction-centered point of view and
      highlights the links between the real world and the virtual world. Based on an OP
      a-S modeling, predictive usability analysis can be performed by considering the
      ergonomic property. We illustrate our method on the retro-design of a computer
      assisted surgical application, CASPER.

PMID- 11317728
TI  - Measurement and display of regional myocardial motion during post infarct
      treatment.
AB  - Quantitative assessment of 3-D regional heart motion has significant potential to
      provide more specific diagnosis of cardiac malfunction than currently possible.
      Using functional parametric mapping, regional myocardial motion during a cardiac
      cycle can be color-mapped onto a deformable heart model to provide better
      understanding of the structure-to-function relationships in the myocardium,
      including regional patterns of akinesis or dyskinesis associated with ischemia or
      infarction. In this study, 3-D reconstructions of human hearts were obtained from
      Electron-Beam Computed Tomography [1] (EB-CT), comparing stages of treatment
      after myocardial infarction.

PMID- 11317729
TI  - Spatial ability and learning the use of an angled laparoscope in a virtual
      environment.
AB  - Little is known about the cognitive demands that underlie surgical performance.
      Several studies have suggested that spatial ability plays a substantial role in
      surgical skill. An example of a skill in which spatial cognition appears to be of
      importance is the use of the angled laparoscope. This paper describes a virtual
      environment designed to assess and train the use of the angled laparoscope. The
      learning rates of novices learning the skill for the first time in the virtual
      environment were measured. The rates were found to be highly variable and
      strongly correlated with spatial ability.

PMID- 11317730
TI  - Wireless vital sign telemetry to hand held computers.
AB  - Most physicians and other health care providers share/access patient information
      via hard copy chart records, telephone conversations, or through hospital
      computer networks. These modalities are cumbersome when physicians are away from
      the hospital and ground wiring infrastructure is not readily available. In a
      prior study, we used wireless in-flight telephony and the Internet to transmit
      vital signs from an airborne Boeing 757 to three remote locations on the ground.
      However, because all recipient stations relied on an institutional network to
      receive the information, it was not possible to transfer data to a given location
      beyond the hospital campus. We now propose an innovative system capable of
      transmitting telemetry information from any location in the globe to a single
      portable computer using Wireless Application Protocol (WAP) technology for the
      Internet. Medical data including blood pressure, pulse, respiratory rate, end
      tidal CO2, oxygen saturation and EKG tracings were transferred from a G2 (digital
      cellular) phone linked to a hand held computer to a remote hand held device and
      were viewed in real time using customized software. Cellular Digital Packet
      Protocols (CDPD) enabled data transfer speeds up to 19,200 bps. Advances
      including the Internet and wireless computer technology may revolutionize the way
      medical information is shared, making it possible for physicians and health
      allies to directly access patient data from anywhere at any time.

PMID- 11317731
TI  - Measurable models of abdominal aortic aneurysm on the Web.
AB  - In this paper we describe a method for 3D reconstruction and web distribution of
      vessel structures specifically designed to allow the remote measurement of
      parameters of surgical interest. Deformable models are used for segmentation,
      while VRML and ECMA scripting are used to obtain 3D models that are not only
      viewable from any VRML97 enabled browser, but that also allow users to interact
      with the model, navigate along the vessel lumen and perform guided measurements
      of distances and angles.

PMID- 11317732
TI  - Virtual simulation system for collision avoidance for medical robot.
AB  - For the collision avoidance with a medical robot with 6 DOF a virtual simulation
      system is presented. Manipulator and obstacles are modelled by geometric
      primitives. Collisions are detected in the Cartesian workspace by hierarchical
      distance computation based on the given CAD model. The application initially
      being addressed is maxillofacial surgery, where the safety of the patient is the
      main requirement,because of the closeness to vital parts. The simulation system
      allows the surgeon to check up the trajectory of the robot before the current
      operation begins.

PMID- 11317733
TI  - A virtual reality surgical trainer for navigation in laparoscopic surgery.
AB  - A virtual reality trainer was designed to familiarize students and surgeons with
      surgical navigation using an angled laparoscopic lens and camera system. Previous
      laparoscopic trainers have been devoted to task or procedure training. Our system
      is exclusively devoted to laparoscope manipulation and navigation. Laparoscopic
      experts scored better than novices in this system suggesting construct validity.
      The trainer received favorable subjective ratings. This simulator may provide for
      improved navigation in the operating room and become a useful tool for residents
      and practicing surgeons.

PMID- 11317734
TI  - Quantification of the gravity-dependent change in the C-arm image center for
      image compensation in fluoroscopic spinal neuronavigation.
AB  - In the quest to develop a viable, frameless spinal navigation system, many
      researchers are utilizing the C-arm fluoroscope. However, there is a significant
      problem with the C-arm that must be quantified: the gravity-dependent sag effect
      resulting from the geometry of the C-arm and aggravated by the inequity of weight
      at each end of the C-arm. This study quantified the C-arm sag effect, giving
      researchers the protocol and data needed to develop a program that accounts for
      this distortion. The development of spinal navigation algorithms that account for
      the C-arm sag effect should produce a more accurate spinal navigation system.

PMID- 11317735
TI  - Real-time anatomical 3D image extraction for laparoscopic surgery.
AB  - Progress in the application of augmented reality to laparoscopic surgery has been
      limited by the difficulty associated with generating geometric information about
      the current patient in real time. Structured light techniques are well known
      methods for generating range images using a camera and projector, but typically
      fail when faced with biological specimens. We describe techniques and equipment
      that have shown promise for acquisition of range images for use in a real-time
      augmented reality system for laparoscopic surgery.

PMID- 11317736
TI  - Force models for needle insertion created from measured needle puncture data.
AB  - The focus of this paper is to present a force-feedback model that has been
      developed for the epidural needle insertion procedure. The model is based on data
      collected from biomaterials testing studies, and consists of separate force
      models for each of the tissue types relevant to the epidural needle insertion
      procedure. These tissue force models were generalized to create force-feedback
      models to drive haptic devices for needle insertion simulation.

PMID- 11317737
TI  - Development of an experimental paradigm in which to examine human learning using
      two computer-based formats.
AB  - Computer-based self-instructional programs are frequently promoted as means to
      augment or replace the traditional anatomy curricula taught in medical schools.
      These programs may range from static slide shows to fully immersive virtual
      environments. However, the impact of these learning technologies on knowledge
      acquisition, and their comparative cost/benefit to education remain unclear. As a
      consequence, we are embarking on a series of experiments to compare knowledge
      acquisition and the meaningful use of information among students who are learning
      anatomy using one of two different computer-based self-instructional formats.
      These studies will be based on a specially developed learning module on basic
      lung anatomy; they will utilize a variety of assessment tools to measure factual
      knowledge, conceptual understanding of spatial-anatomic relationships, and the
      ability to apply newly acquired knowledge of anatomy to clinical problem-solving
      scenarios. The primary object of this paper is to describe the design and
      development of the underlying test module and to outline the two computer-based
      formats that will be evaluated. The virtual reality (VR) environment, UCSD's
      Anatomic VisualizeR, provides dynamic access to 3-dimensional polygonal models of
      the lesson content and supports student-centered exploration and learning. The
      multimedia environment, Microsoft PowerPoint, provides a structured presentation
      of the lesson content and illustrates important anatomic structures through the
      use of 2-dimensional images derived by screen captures of models available in the
      VR learning module. This paper also provides an overview of the first experiment
      in the series, a pilot study using first-year medical students without previous
      participation in a medical school anatomy curriculum. For this study, students
      will be prospectively randomized into two groups, each group learning the lung
      anatomy lesson using one of the computer-based formats described. Immediate
      knowledge retention will be measured by asking students to complete the
      assessment instrument immediately after completing their learning module. The
      results of the pilot study will be used to refine and improve the design of the
      remainder of studies planned in this experimental series.

PMID- 11317738
TI  - Retraining movement in patients with acquired brain injury using a virtual
      environment.
AB  - We report preliminary results of an ongoing study in which a virtual environment
      (VE) system is used to facilitate motor relearning of a pouring task in patients
      with Acquired Brain Injury (ABI). Four subjects were evaluated pre- and post-VE
      training using virtual-world and real-world tests in which subjects performed a
      pouring motion while holding a cup. Standard clinical tests of motor and
      functional ability were also used. Three of four subjects demonstrated
      improvement in end-point trajectories (cup path) performed during the virtual and
      real world tests. Clinical test scores also improved. Results indicate that
      subjects with ABI were able to learn a movement in VE, and generalize this
      ability to real-world performance of similar and unrelated tasks. VE training
      appears to be a feasible and promising approach to the rehabilitation of subjects
      with ABI.

PMID- 11317739
TI  - 3D localization of implanted radioactive sources in the prostate using trans
      urethral ultrasound.
AB  - Prostate cancer is the most common cancer diagnosed in men in the United States.
      Many techniques have been developed to diagnose and treat prostate cancer. 3D
      Trans-Urethral Ultrasound (TUUS) is a new technique for the diagnosis and
      treatment of prostate disease. This research focuses on the potential of TUUS for
      therapy-guidance during and after transperineal interstitial permanent prostate
      brachytherapy (TIPPB). Computed tomography (CT) is currently used to determine
      the source locations and the effective radiation dose distribution throughout the
      tissue after the completion of the procedure. TUUS may be a viable alternative to
      CT for determining source locations within the prostate. Placement of the TUUS
      catheter into the urethra provides excellent 2D images of the prostate. In
      addition, the catheter can be used to acquire 3D volumetric data for 3D analysis
      of the prostate, associated tissue, and radioactive sources. Initial work on
      source localization was conducted on an ultrasound-equivalent prostate phantom.
      Cylindrical dummy radiation sources with diameter of .8 mm and length of 4.5 mm
      were placed into the prostate phantom for assessment with TUUS. The TUUS imaging
      device is a 10 fr catheter with a linear array of ultrasonic crystals at one end.
      The ultrasound catheter operates at 10 MHz and is controlled by the Acuson
      Sequoia ultrasound workstation. The catheter was placed in the phantom urethra
      and 3D scans were acquired. A corresponding CT was acquired for comparative
      purposes. Segmentation of the prostate capsule was done semi-automatically. Dummy
      radiation seed segmentation was conducted manually. Additional processing was
      necessary to account for image artifact and correctly reconstruct the seeds. The
      prostate shell and radioactive source reconstructions provide an excellent 3D
      representation. Comparison to the CT data suggests that the TUUS data provided:
      1) greater resolution and 2) better soft tissue differentiation. The
      reconstructed sources were measured and corresponded to the physical dimensions
      of those placed in the phantoms. The method is now being evaluated on cadavers
      and patients.

PMID- 11317740
TI  - Intraoperative visualization of surgical planning data using video projectors.
AB  - The Institute for Process Control and Robotics has developed a new system using
      projector based augmented reality for the intraoperative visualization of
      preoperatively defined surgical planning data. Projector based augmented reality
      in medical applications represents a new field of research and gives an
      alternative solution to the commonly used Head Mounted Display technology.
      Moreover, the projector is not only used for visualization, but also for
      registration of the patient without the usage of invasive fiducial techniques as
      e.g. screw markers or frames. Recent results showed an achieved accuracy of +/-
      1.5 mm which roughly meets clinical demands.

PMID- 11317741
TI  - The development of the virtual reality system for the treatment of the fears of
      public speaking.
AB  - The fear of public speaking is a kind of social phobias. The patients having the
      fear of public speaking show some symptoms like shame and timidity in the daily
      personal relationship. They are afraid that the other person would be puzzled,
      feel insulted, and they also fear that they should be underestimated for their
      mistakes. For the treatment of the fear of public speaking, the cognitive
      behavioral therapy has been generally used. The cognitive-behavioral therapy is
      the method that makes the patients gradually experience some situations inducing
      the fears and overcome those at last. Recently, the virtual reality technology
      has been introduced as an alternative method for providing phobic situations. In
      this study, we developed the public speaking simulator and the virtual
      environments for the treatment of the fear of public speaking. The head-mounted
      display, the head-tracker and the 3 dimensional sound system were used for the
      immersive virtual environment. The imagery of the virtual environment consists of
      a seminar room and 8 virtual audiences. The patient will speak in front of these
      virtual audiences and the therapist can control motions, facial expressions,
      sounds, and voices of each virtual audience.

PMID- 11317742
TI  - Web-based surgical educational tools.
AB  - This paper describes work being undertaken as part of the WebSET (Web-based
      Standard Educational Tools) project. The project is producing a standardised
      suite of interactive three-dimensional educational tools, delivered across the
      WWW. The major focus will be the use of open technology and standards, and the
      production of learning components that can be used as building blocks for further
      development in a wide range of application areas. Two learning disciplines have
      been selected for the development of the WebSET tools: surgical training, and
      physiological education. A high quality consortium from across Europe has been
      assembled with complementary skills in the technologies needed by the project.
      The project is partly funded by the European Commission.

PMID- 11317743
TI  - An integrated simulator for surgery of the petrous bone.
AB  - This paper describes work being undertaken as part of the IERAPSI (Integrated
      Environment for the Rehearsal and Panning of Surgical Intervention) project. The
      project is focussing on surgery for the petrous bone, and brings together a
      consortium of European clinicians and technology providers working in this field.
      The paper presents the results of a comprehensive user task analysis that has
      been carried out in the first phase of the IERAPSI project, and details the
      current status of development of a pre operative planning environment and a
      physically-based surgical simulator.

PMID- 11317744
TI  - Virtual fluoroscopy: a tool for decreasing radiation exposure during femoral
      intramedullary nailing.

PMID- 11317745
TI  - Ghost imaging in MRI.
AB  - Needle biopsies and other interventions done under MR Fluoroscopy sometimes do
      not show the target well, either because the rapid sequence does not have
      adequate contrast or because a contrast agent may have washed out of the target.
      In these cases, an image that shows the target can be saved and scaled to match
      the spatial parameters of the fluoroscopic sequence, and used as a virtual or
      ghost field upon which the fluoroscopic images are superimposed, thus providing a
      view of the target, useful for needle pre-localization and for monitoring its
      progress as it is inserted.

PMID- 11317746
TI  - An integrated environment for stereoscopic acquisition, off-line 3D elaboration,
      and visual presentation of biological actions.
AB  - We present an integrated environment for stereoscopic acquisition, off-line 3D
      elaboration, and visual presentation of biological hand actions. The system is
      used in neurophysiological experiments aimed at the investigation of the
      parameters of the external stimuli that mirror neurons visually extract and match
      on their movement related activity.

PMID- 11317747
TI  - Trauma training: virtual reality applications.
AB  - Training medics, medical students, nurses, and residents to perform trauma care
      skills presents many obstacles. These include: emergent nature of the procedures,
      instructor time, availability of clinical material, and anatomic knowledge.
      Virtual Reality simulators address each of these obstacles. The National Capital
      Area Medical Simulation Center is a unique national asset that not only uses
      state-of-the-art simulators to teach trauma care skills to medical students and
      others, but adapts existing technology and develops new simulations to teach
      these skills. Most standard trauma training is performed on either mannequins or
      anesthetized animals and requires the constant presence of an instructor. VR
      applications can be stand-alone devices that have built-in scenarios and multiple
      patients to increase variation and/or level of technical expertise required to
      successfully complete the required steps of the trauma procedure. Commercial VR
      simulators to teach trauma skills include: CathSim Intravenous Simulator (HT
      Medical), UltraSim Ultrasound Simulator (MedSim), Limb Trauma Simulator
      (Musculographics/BDI), and the Human Patient Simulator (MedSim). Additionally, we
      have developed two additional simulators based on the HT CathSim; these are the
      pericardiocentesis simulator and the diagnostic peritoneal lavage simulator.
      Future applications include virtual environment triage simulation and surgical
      airway simulators.

PMID- 11317748
TI  - Computer assisted treatment of pelvis fractures.
AB  - The presented approach is the realization of a minimal invasive treatment of
      pelvis fractures using the computer aided surgery (CAS). Main problem of tracking
      of major bone fragments after reposition is solved by implementing of 3D
      ultrasound to obtain intraoperative bone surfaces. Preoperative and
      intraoperative data sets are matched. Major fragments are tracked. The real time
      navigation is possible.

PMID- 11317749
TI  - Computer simulation of osteotomy correction.
AB  - This paper describes a novel approach to correct osteotomy deformities of long
      bones using virtual reality and image processing techniques on personal
      computers. The discussed method allows to simulate osteotomy corrections by
      implementing a single cut and a rearrangement of the dissected bone parts. It
      allows the surgeon to directly control the pre-operative situation and the post
      operative result of the simulation by comparing bone-length, angles, and torsion
      of the bone. In addition, he or she obtains the coordinates and angles of the
      planned cut relative to anatomical landmarks.

PMID- 11317750
TI  - Development of virtual environment for treating acrophobia.
AB  - Virtual Reality (VR) is a new technology that makes humans communicate with
      computer. It allows the user to see, hear, feel and interact in a three
      dimensional virtual world created graphically. Virtual Reality Therapy (VRT),
      based on this sophisticated technology, has been recently used in the treatment
      of subjects diagnosed with acrophobia, a disorder that is characterized by marked
      anxiety upon exposure to heights, avoidance of heights, and a resulting
      interference in functioning. Conventional virtual reality system for the
      treatment of acrophobia has a limitation in scope that it is based on over-costly
      devices or somewhat unrealistic graphic scene. The goal of this study was to
      develop a inexpensive and more realistic virtual environment for the exposure
      therapy of acrophobia. We constructed two types virtual environment. One is
      constituted a bungee-jump tower in the middle of a city. It includes the open
      lift surrounded by props beside tower that allowed the patient to feel sense of
      heights. Another is composed of diving boards which have various heights. It
      provides a view of a lower diving board and people swimming in the pool to serve
      the patient stimuli upon exposure to heights.

PMID- 11317751
TI  - An endoscopic navigation system.
AB  - Endoscopy is an important procedure for the diagnostic and therapy of various
      pathologies. We develop extensive and automated systems for this field. Due to
      application of these new systems, a patient is subject to considerably less
      strains, as opposed to prevailing commercial systems. The capability of such
      instruments, unlike the presently used systems, to independently follow
      anatomical peculiarities of the body means also a reduced risk of complications
      for a patient. A further advantage is that difficult to access regions deep
      inside the body, like the small intestine or peripheral parts of the bronchial
      tubes, can thus be reached. We use a complex navigation system for our new
      endoscopic system.

PMID- 11317752
TI  - The Virtual Brain Project--development of a neurosurgical simulator.
AB  - As a joined project between Aalborg University and Aalborg Hospital Denmark, a
      neuro-surgical simulator is being developed. In this paper the objective of the
      project is outlined and an overview of the research activities within the project
      is given. Focus is on 3D modelling of the brain, deformable models and the
      development of two demonstrators, including one for training of punctuation of
      ventricle using visual and haptic feedback.

PMID- 11317753
TI  - An open and flexible framework for computer aided surgical training.
AB  - During the past year we have developed a new surgical skills training application
      called LapSim. We intend to describe the design, architecture and concepts of the
      software framework we have developed concurrently with the application. The
      framework is based on the concept of a classroom with students and teachers.
      Students, courses and results are stored in a centralized database and can be
      retrieved for review or modification. The students can also monitor their
      progress relative to other students or experts.

PMID- 11317754
TI  - Intracorporeal suturing and knot tying in surgical simulation.
AB  - Intracorporeal suturing and knot tying is one of the most difficult tasks to
      perform during minimally invasive surgery. To master these tasks the student
      requires extensive training in a real or simulated environment. Realistic
      simulation of suturing and knot tying is a challenging task, the dynamic
      behaviors of the needle and thread are complicated to calculate efficiently in
      real time. We present our approach to simulated training of intracorporeal
      suturing and knot tying as well as our method for performance assessment.
      Different algorithms for physical modeling of suture thread dynamics are examined
      and evaluated.

PMID- 11317755
TI  - Automatic skeleton generation for visualizing 3D, time-dependent fluid flows:
      application to the virtual aneurysm.
AB  - Intracranial aneurysms are the primary cause of non-traumatic subarachnoid
      hemorrhage. Difficulties in identifying which aneurysms will grow and rupture
      arise because the physicians lack important anatomic and hemodynamic information.
      Through simulation, this data can be captured, but visualization of large
      simulated data sets becomes cumbersome, often resulting in visual clutter and
      ambiguity. To address these visualization issues, we developed an algorithm that
      extracts a skeleton of the patterns in 3D, time-dependent blood flow. The
      algorithm decomposes the blood flow into "bare-bones" components that can be
      visualized individually or superimposed together to formulate an understanding of
      the flow patterns in the aneurysm.

PMID- 11317756
TI  - A computer-based simulator for diagnostic peritoneal lavage.
AB  - Diagnostic peritoneal lavage (DPL) is an emergency diagnostic procedure performed
      when intra-abdominal bleeding secondary to trauma is suspected. This procedure is
      part of the surgical skills section of the Advanced Trauma Life Support course.
      DPL is traditionally taught using anesthetized animals or cadavers. For reasons
      described below, these alternatives are not ideal. We have developed a computer
      based diagnostic peritoneal lavage simulator. Our system addresses the
      shortcomings of the traditional method. We have used our system to teach ATLS.
      Preliminary results suggests that our system is effective.

PMID- 11317757
TI  - Effects of geared motor characteristics on tactile perception of tissue
      stiffness.
AB  - Endoscopic haptic surgical devices have shown promise in addressing the loss of
      tactile sensation associated with minimally invasive surgery. However, these
      devices must be capable of generating forces and torques similar to those applied
      on the tissue with a standard endoscopic tool. Geared motors are a possible
      solution for actuation; however, they possess mechanical characteristics that
      could potentially interfere with tactile perception of tissue qualities. The aim
      of the current research was to determine how the characteristics of a geared
      motor suitable for a haptic surgical device affect a user's perception of
      stiffness. The experiment involved six blindfolded subjects who were asked to
      discriminate the stiffness of six distinct silicone rubber samples whose
      mechanical properties are similar to those of soft tissue. Using a novel testing
      device whose dimensions approximated those of an endoscopic grasper, each subject
      palpated 30 permutations of sample pairs for each of three types of mechanical
      loads; the motor (friction and inertia), a flywheel (with the same inertia as
      motor), and a control (no significant mechanical interference). One factor ANOVA
      of the error scores and palpation time showed that no significant difference
      existed among error scores, but mean palpation time for the control was
      significantly less than for the other two methods. These results indicated that
      the mechanical characteristics of a geared motor chosen for application in a
      haptic surgical device did not interfere with the subjects' perception of the
      silicone samples' stiffness, but these characteristics may significantly affect
      the energy expenditure and time required for tissue palpation. Therefore, before
      geared motors can be considered for use in haptic surgical devices, consideration
      should be given to factors such as palpation speed and fatigue.

PMID- 11317758
TI  - Using immersive VR as a tool for preoperative planning for minimally invasive
      donor nephrectomy.
AB  - For surgeons approaching minimally invasive donor nephrectomy it is important to
      identify variant anatomy preoperatively since this anatomy can vary significantly
      from patient to patient. The goal of this operation is to preserve the
      architecture and function of the organ so it can be transplanted and function
      successfully. The ability of the surgeon to navigate through an individual
      patient's anatomy in a virtual three-dimensional (3D) immersive environment
      augments understanding of anatomical relationships particular to that individual
      patient and facilitates conveying that information to other physicians and
      students. Utilizing automated 3D reconstruction of high contrast computed
      tomography (CT) scan files viewed in this way, surgeons reported a better
      preoperative understanding of the anatomical variations and encountered fewer
      surprises at the time of surgery.

PMID- 11317759
TI  - Digital motion phenomenology of depression.
AB  - The long-term objective of our project is to use motion capture technology to
      identify and characterize body alterations in motion associated with depression
      that have not been previously recognized or characterizable. These motion
      phenomena will be studied to determine their utility in the nosology and
      subtyping of depression. Quantitatively, they may have a significant impact in
      the areas of research, education and the clinical management of depression; and
      allow the creation of "virtual humans" which manifest depressive digital motion
      phenomena that can be used to train researchers, trainees and clinicians.

PMID- 11317760
TI  - Virtual eye muscle surgery based upon biomechanical models.
AB  - Within our research project "SEE-KID", a Software Engineering Environment for
      Knowledge-based Interactive Eye Motility Diagnostics, we focus on virtual reality
      training for the surgery of human eye muscles of--mostly--children age 1 to 3.
      Our report gives details on the sound integration of biomechanical muscle data
      into our virtual reality models in order to evaluate the quality of specific
      techniques for eye motility surgery regarding real-world pathologies. We
      illustrate the usefulness of our software system describing some of the possible
      medical applications, like optimized transposition surgery of the musculus
      obliquus superior.

PMID- 11317761
TI  - Development of an international net-based medical information system for advanced
      surgical education.

PMID- 11317762
TI  - Virtual reality based surgical assistance and training system for long duration
      space missions.
AB  - Access to medical care during long duration space missions is extremely
      important. Numerous unanticipated medical problems will need to be addressed
      promptly and efficiently. Although telemedicine provides a convenient tool for
      remote diagnosis and treatment, it is impractical due to the long delay between
      data transmission and reception to Earth. While a well-trained surgeon-internist
      astronaut would be an essential addition to the crew, the vast number of
      potential medical problems necessitate instant access to computerized, skill
      enhancing and diagnostic tools. A functional prototype of a virtual reality based
      surgical training and assistance tool was created at our center, using low-power,
      small, lightweight components that would be easy to transport on a space mission.
      The system consists of a tracked, head-mounted display, a computer system, and a
      number of tracked surgical instruments. The software provides a real-time
      surgical simulation system with integrated monitoring and information retrieval
      and a voice input/output subsystem. Initial medical content for the system has
      been created, comprising craniofacial, hand, inner ear, and general anatomy, as
      well as information on a number of surgical procedures and techniques. One
      surgical specialty in particular, microsurgery, was provided as a full simulation
      due to its long training requirements, significant impact on result due to
      experience, and likelihood for need. However, the system is easily adapted to
      realistically simulate a large number of other surgical procedures. By providing
      a general system for surgical simulation and assistance, the astronaut-surgeon
      can maintain their skills, acquire new specialty skills, and use tools for
      computer-based surgical planning and assistance to minimize overall crew and
      mission risk.

PMID- 11317763
TI  - Military medical modeling and simulation in the 21st century.
AB  - As we enter the 21st century, military medicine struggles with critical issues.
      One of the most important issues is how to train medical personnel in peace for
      the realities of war. In April, 1998, The General Accounting Office (GAO)
      reported, "Military medical personnel have almost no chance during peacetime to
      practice battlefield trauma care skills. As a result, physicians both within and
      outside the Department of Defense (DOD) believe that military medical personnel
      are not prepared to provide trauma care to the severely injured soldiers in
      wartime. With some of today's training methods disappearing, the challenge of
      providing both initial; and sustainment training for almost 100,000 military
      medical personnel is becoming insurmountable. The "training gap" is huge and
      impediments to training are mounting. For example, restrictions on animal use are
      increasing and the cost of conducting live mass casualty exercises is
      prohibitive. Many medical simulation visionaries believe that four categories of
      medical simulation are emerging to address these challenges. These categories
      include PC-based multimedia, digital mannequins, virtual workbenches, and total
      immersion virtual reality (TIVR). The use of simulation training can provide a
      risk = free realistic learning environment for the spectrum of medical skills
      training, from buddy-aid to trauma surgery procedures. This will, in turn,
      enhance limited hands on training opportunities and revolutionize the way we
      train in peace to deliver medicine in war. High-fidelity modeling will permit
      manufacturers to prototype new devices before manufacture. Also, engineers will
      be able to test a device for themselves in a variety of simulated anatomical
      representations, permitting them to "practice medicine".

PMID- 11317764
TI  - New graphics models for PC based ocular surgery simulator.
AB  - High-end graphics workstations (GWS) have been used for surgical simulators
      utilizing Computer Graphics (CG) and Virtual Reality (VR) technologies. This is
      because the simulators need lots of computing power, mainly for collision
      detection among objects modeled as a set of polygons. In this paper, we propose
      to use mathematical functions to model objects for collision detection. However,
      for graphic display we continue to use polygonal representation. Using the new
      model, we have developed a PC based ocular surgery simulator, which creates
      realistic surgery image in real-time. The computation time was found to be much
      lower than that in the conventional method.

PMID- 11317766
TI  - MEDNET: a medical simulation network grand challenge.
AB  - The need to improve war-fighter training led to significant advancements in
      simulator technology. Now, simulator technology is ready to be applied to a new
      challenge: an evolutionary approach to training military medical personnel that
      will result in improved combat casualty care. With the exception of the
      introduction of helicopter evacuation support during the Korean War, changes in
      combat casualty care have not significantly altered the percentage of wounded
      soldiers lost in combat since World War II. The introduction of battlefield
      simulator training has improved strategic planning and combat readiness. It is
      time to apply these same tools to improve medical planning, military medical
      readiness and execution of casualty care.

PMID- 11317765
TI  - LAHYSTOTRAIN development and evaluation of a complex training system for
      hysteroscopy.
AB  - Hysteroscopy has already become an irreplaceable method in gynaecoloic diagnosis
      and therapy. In the diagnostic case the hysteroscope with a 30 degrees optic is
      insert transvaginally, in the therapeutic case the resectoscope with a 12 degrees
      optic is used. The endoscopic intervention requires special surgical skills for
      endoscope handling and remote instrument control. To acquire these skills
      currently hands-on training in clinical praxis has become standard, which is
      linked with higher danger for the women. To overcome current drawbacks of
      traditional training methods the European project LAHYSTOTRAIN was set up, that
      tries to combine Virtual Reality (VR), Multimedia (MM) technology, and
      Intelligent Tutoring Systems (ITS) to develop an alternative training system for
      hysteroscopic interventions. The first prototype of the LAHYSTOTRAIN demonstrator
      has been shown on several European conferences. An evaluation of the system was
      performed, with the idea, to collect feedback and impressions, that should be
      considered in further developments. This paper presents the LAHYSTOTRAIN
      prototype and the results of these evaluations.

PMID- 11317767
TI  - Laser-pointing endoscope system for natural 3D interface between robotic
      equipments and surgeons.
AB  - Precise measurements of reference points would be mandatory of robotic equipments
      would be introduced in operation rooms. We develop a real-time laser-pointing
      endoscope using an optical galvano scanner and a 955fps high-speed camera. This
      system provides the scanned 3D image of the liver under the endoscopic surgery
      and a touch screen interface so that surgeons can intuitively indicate points of
      interest with precise 3D position. Some results of in-vivo experiments on a liver
      of pig are shown to verify the effectiveness of the proposed.

PMID- 11317768
TI  - Robotic stabilization that assists cardiac surgery on beating hearts.
AB  - Minimally Invasive Direct Coronary Artery Bypass (MIDCAB) requires surgeons the
      precision of hand skill and the mental concentration, since it needs to work on
      beating hearts. We propose a surgical robot system that compensates motions of
      organs during operations. The motion canceling robot system consists of three
      technologies visual synchronization, motion synchronization and master slave
      control. In this paper, we verify the effectiveness of the prototype system by in
      vivo experiment.

PMID- 11317769
TI  - 4D visible and palpable simulation using dynamic pressure model based on cardiac
      morphology.
AB  - A goal of this work is proposal and construction of ActiveHeart System: a
      simulation environment that enables anyone to see and touch heart beat in real
      time. In this paper, a method to express real-time graphic and haptic behaviour
      of a beating heart is mentioned. The data for the beating heart model was
      obtained from ECG-gated 3D MRI of a normal volunteer. The elastic information was
      assumed as a uniform value with clinically experienced elasticity. Using a real
      time 3D graphics and a haptic device, a simulation environment of the beating
      heart was designed and implemented. After the construction, some cardiovascular
      surgeons evaluated the implemented system. Its visualization and beating
      expression were scored excellent, but some details in haptic expression were
      remained to be improved. Finally, for more realistic cardiovascular surgical
      simulation, future development of the method is discussed.

PMID- 11317770
TI  - The representation of blood flow in endourologic surgical simulations.
AB  - An image-based approach has been developed to represent bleeding in a simulator
      for transurethral resection of prostate (TURP). While previous attempts have
      simulated bleeding over tissue surfaces or in blood vessels, our approach focused
      on the macroscopic visualization of bleeding in a fluid environment. TURP is an
      ideal procedure for simulation-based training because of the dynamic environment
      and the variety of flow patterns it presents. The first step in the development
      of the simulator was the generation of blood flow movies which consisted of
      capturing videos of bleeding vessels in vitro, processing them to separate the
      actual blood from the background anatomy and organizing the movies into a
      parametric database. During the running of the simulation, resection of prostate
      tissue systematically triggers bleeding events and the playback of a blood flow
      movie. The blood flow movie is texture mapped onto a virtual surface that is
      positioned oriented, morphed, composited and looped into the virtual scene.

PMID- 11317771
TI  - An experiment on fear of public speaking in virtual reality.
AB  - Can virtual reality exposure therapy be used to treat people with social phobia?
      To answer this question it is vital to known if people will respond to virtual
      humans (avatars) in a virtual social setting in the same way they would to real
      humans. If someone is extremely anxious with real people, will they also be
      anxious when faced with simulated people, despite knowing that the avatars are
      computer generated? In [17] we described a small pilot study that placed 10
      people before a virtual audience. The purpose was to assess the extent to which
      social anxiety, specifically fear of public speaking, was induced by the virtual
      audience and the extent of influence of degree of immersion (head mounted display
      or desktop monitor. The current paper describes a follow up study conducted with
      40 subjects and the results clearly show that not only is social anxiety induced
      by the audience, but the degree of anxiety experienced is directly related to the
      type of virtual audience feedback the speaker receives. In particular, a hostile
      negative audience scenario was found to generate strong affect in speakers,
      regardless of whether or not they normally suffered from fear of public speaking.

PMID- 11317772
TI  - Exploring the visible human's inner organs with the VOXEL-MAN 3D navigator.
AB  - Improved rendering and segmentation techniques lead to a new quality of 3D
      reconstructions of the Visible Human. Using these we have implemented an
      interactive atlas of anatomy and radiology of the inner organs.

PMID- 11317773
TI  - Internet as an "honest" management tool first experience in a national institute
      of health and social services in Argentina.
AB  - The PAMI's website creation (www.pami.org.ar) has had the purpose of spreading
      its activities, the standards of medical care and administrative management,
      offering--at the same time--a honest channel of interaction with the community.

PMID- 11317774
TI  - Virtual Reality as an assessment tool for arm motor deficits after brain lesions.
AB  - The currently used assessment techniques for measuring neurological deficits are
      time consuming and may lack of sensibility and repeatability. Previous studies
      suggested that the cinematic analysis of the movement, might represent a reliable
      alternative instrument for documenting the degree of motor impairment. To verify
      this hypothesis we investigated motor/functional progress in 20 post-stroke
      patients, undergoing rehabilitation therapy, by means of a widely used clinical
      test (Fugl-Meyer scale), and by evaluating kinematics of arm motion. After
      rehabilitation therapy, velocity and duration of reaching movements significantly
      improved with respect to baseline values. Before and after rehabilitation there
      was a significant correlation between each cinematic parameter and the clinical
      scale scores. These results, suggests that the cinematic analysis of movement can
      be proposed as a precise and objective assessment tool to be used in clinical
      practice.

PMID- 11317775
TI  - Multislice CT and Computational Fluid Dynamics: a new technique to visualize,
      analyze and simulate hemodynamics in aortic aneurysms and stentgrafts.

PMID- 11317776
TI  - The effect of simulator use on learning and self-assessment: the case of Stanford
      University's E-Pelvis simulator.

PMID- 11317777
TI  - CompAc information system for traditional Chinese medicine.
AB  - The paper presents a system developed for the assistance of diagnosis and
      treatment in alternative medicine, based on traditional Chinese methods. The
      system named CompAc, is a result of an interdisciplinary cooperation and is
      designed for the physician, specialist in acupuncture. The Compac system allows
      the determination of the type of energetic imbalance starting from the clinical
      picture of the patient and establishing whether an organ or any of the viscera
      are affected. It allows also the indication of different variants of treatment.
      The diagnosis proposed by the system has to be confirmed by the physician and can
      be modified by him. The system is also useful for medical training.

PMID- 11317778
TI  - Force-feedback in Web-based surgical simulators.
AB  - There is a growing requirement in the field of surgical training to allow
      trainees to practice procedures in a way that does not place patients in any
      risk. Computer based simulators allow students to gain experience and develop
      three-dimensional awareness in a safe and controlled environment. Typically
      systems that have been developed to perform this task are, due to their
      specialist nature, expensive to buy. With the increasing availability of Force
      Feedback devices for the gaming market, is there now a cost-effective alternative
      for surgical simulations? In this paper we investigate the possibility of using
      such a device as a haptic input tool for surgical simulations.

PMID- 11317779
TI  - A survey study for the development of virtual reality technologies in
      orthopedics.
AB  - Virtual reality (VR) technologies have the potential to support medical education
      and training. In order to orient the development of medical VR applications
      towards the actual deficiencies and demands in orthopedics, we performed a survey
      among 56 orthopedic physicians. They were asked to provide information about the
      kind of physical joint evaluation tests which they perform most often, the
      importance of physical joint evaluation in comparison to alternative diagnostic
      methods, and their opinion about current medical education system as well as the
      prospects of VR applications in orthopedics. The main conclusion of this survey
      is that VR applications have the potential to improve the lacking medical
      education and orthopedic training, e.g. by improving the quality of joint
      evaluation methods, reducing the high number of unhealthy, risky and expensive
      alternative diagnostic procedures.

PMID- 11317780
TI  - Telemedicine used in a simulated disaster response.
AB  - In June 2000, the Telemedicine Center at the Brody School of Medicine, East
      Carolina University in Greenville, NC participated in a simulated disaster
      response in Pu'u Paa, Hawaii, a lava plain without running water, electricity, or
      human habitation. During the five-day exercise we evaluated the ability to
      establish telecommunications and the effectiveness of the infrastructure,
      services, and applications implemented for an operational global emergency
      response. Scaleable technologies were configured and systematically tested to
      determine the ability to provide medical and health care in an austere
      environment. A medical communications matrix was constructed and used throughout
      the evaluation. Results show that telemedicine can be an important contribution
      to humanitarian relief efforts and medical support following disasters.
      Additional research is needed to build upon the lessons learned from
      participation in this exercise.

PMID- 11317781
TI  - Development of a multi-modal virtual human knee joint for education and training
      in orthopaedics.
AB  - Due to limited simultaneous access to a greater pool of patients an effective
      training of medical students or young orthopedic physicians is difficult. A knee
      joint simulator that comprises the properties of a healthy or pathological knee
      can support medical education and training. In this paper a mechatronic system is
      presented that provides visual, acoustic, and haptic (force) feedback so that it
      allows a user to touch and move a virtual shank, bones or muscles within the leg,
      and simultaneously observe the generated movement, feel the contact force, and
      hear sounds. These and further features enable the user to study and assess the
      properties of the knee, e.g. by testing the joint laxity and end-point stiffness
      in six degrees-of-motion (DOF) and by grasping and pulling at muscles, rupturing
      ligaments or changing muscle/ligament paths. Such a tool can support training of
      physical knee evaluation required for diagnosis and therapeutic planning, since
      any kind of pathology of any subject type can be tested at any time. Furthermore,
      it can provide a better understanding of functional anatomy, e.g. for the
      education of medical students.

PMID- 11317782
TI  - Objective laparoscopic skills assessments of surgical residents using Hidden
      Markov Models based on haptic information and tool/tissue interactions.
AB  - Laparoscopic surgical skills evaluation of surgery residents is usually a
      subjective process, carried out in the operating room by senior surgeons. By its
      nature, this process is performed using fuzzy criteria. The objective of the
      current study was to develop and assess an objective laparoscopic surgical skill
      scale using Hidden Markov Models (HMM) based on haptic information, tool/tissue
      interactions and visual task decomposition. METHODS: Eight subjects (six surgical
      trainees: first year surgical residents 2 x R1, third year surgical residents 2 x
      R3 fifth year surgical residents 2 x R5; and two expert laparoscopic surgeons: 2
      x ES) performed laparoscopic cholecystectomy following a specific 7 steps
      protocol on a pig. An instrumented laparoscopic grasper equipped with a three
      axis force/torque sensor located at the proximal end with an additional force
      sensor located on the handle, was used to measure the forces and torques. The
      hand/tool interface force/torque data was synchronized with a video of the tool
      operative maneuvers. A synthesis of frame-by-frame video analysis was used to
      define 14 different types of tool/tissue interactions, each one associated with
      unique force/torque (F/T) signatures. HMMs were developed for each subject
      representing the surgical skills by defining the various tool/tissue interactions
      as states and the associated F/T signatures as observations. The statistical
      distance between the HMMs representing residents at different levels of their
      training and the HMMs of expert surgeons were calculated in order to generate a
      learning curve of selected steps during laparoscopic cholecystectomy. RESULTS:
      Comparison of HMM's between groups showed significant differences between all
      skill levels, supporting the objective definition of a learning curve. The major
      differences between skill levels were: (i) magnitudes of F/T applied (ii) types
      of tool/tissue interactions used and the transition between them and (iii) time
      intervals spent in each tool/tissue interaction and the overall completion time.
      The objective HMM analysis showed that the greatest difference in performance was
      between R1 and R3 groups and then decreased as the level of expertise increased,
      suggesting that significant laparoscopic surgical capability develops between the
      first and the third years of their residency training. The power of the
      methodology using HMM for objective surgical skill assessment arises from the
      fact that it compiles enormous amount of data regarding different aspects of
      surgical skill into a very compact model that can be translated into a single
      number representing the distance from expert performance. Moreover, the
      methodology is not limited to in-vivo condition as demonstrated in the current
      study. It can be extended to other modalities such as measuring performance in
      surgical simulators and robotic systems.

PMID- 11317783
TI  - Digital trainer developed for robotic assisted cardiac surgery.
AB  - Robotic systems for cardiac surgery have been introduced in clinical trials to
      facilitate minimally invasive techniques. Widespread use of surgical robotics
      necessitates new training methods to improve skills and continue practicing as
      the robotic systems are frequently being upgraded. Today, robotic training is
      performed on expensive animal models. An integration of a digital trainer with
      the two present robotic systems applied in coronary artery bypass procedures on
      beating heart requires real time simulation of tissue mechanics, sutures,
      instruments and bleeding. However, it requires no extra haptic device, since the
      robotic master is the haptic apparatus itself. By developing new data structures
      and parametric geometry descriptions we have demonstrated the possibility of
      obtaining surgical simulation on a standard PC Linux system. This technology is
      beneficial when simulation is exploited over a network with limited bandwidth,
      especially when it comes to the handling of soft tissue dynamics.

PMID- 11317784
TI  - A new portable equipment for detection of psychophysical conditions.
AB  - This paper deals with the Disease Detector (DDX) that is a virtual reality
      control system for detection of Parkinson disease. The control system consists of
      a small board with an internal fuzzy micro controller capable of acquiring,
      through the joystick, the well known three basic parameters (reaction, speed and
      force) in order to detect the state of health and perform them by fuzzy rules.
      The resulting output can be visualized through a display or transmitted by a
      communication interface.

PMID- 11317785
TI  - 3D visualization and stereographic techniques for medical research and education.
AB  - While computers have been able to work with true 3D models for a long time, the
      same does not apply to the users in common. Over the years, a number of 3D
      visualization techniques have been developed to enable a scientist or a student,
      to see not only a flat representation of an object, but also an approximation of
      its Z-axis. In addition to the traditional flat image representation of a 3D
      object, at least four established methodologies exist: Stereo pairs. Using image
      analysis tools or 3D software, a set of images can be made, each representing the
      left and the right eye view of an object. Placed next to each other and viewed
      through a separator, the three dimensionality of an object can be perceived.
      While this is usually done on still images, tests at Mednet have shown this to
      work with interactively animated models as well. However, this technique requires
      some training and experience. Pseudo3D, such as VRML or QuickTime VR, where the
      interactive manipulation of a 3D model lets the user achieve a sense of the
      model's true proportions. While this technique works reasonably well, it is not a
      "true" stereographic visualization technique. Red/Green separation, i.e. "the
      traditional 3D image" where a red and a green representation of a model is
      superimposed at an angle corresponding to the viewing angle of the eyes and by
      using a similar set of eyeglasses, a person can create a mental 3D image. The end
      result does produce a sense of 3D but the effect is difficult to maintain.
      Alternating left/right eye systems. These systems (typified by the StereoGraphics
      CrystalEyes system) let the computer display a "left eye" image followed by a
      "right eye" image while simultaneously triggering the eyepiece to alternatively
      make one eye "blind". When run at 60 Hz or higher, the brain will fuse the
      left/right images together and the user will effectively see a 3D object.
      Depending on configurations, the alternating systems run at between 50 and 60 Hz,
      thereby creating a flickering effect, which is strenuous for prolonged use.
      However, all of the above have one or more drawbacks such as high costs, poor
      quality and localized use. A fifth system, recently released by Barco Systems,
      modifies the CrystalEyes system by projecting two superimposed images, using
      polarized light, with the wave plane of the left image at right angle to that of
      the right image. By using polarized glasses, each eye will see the appropriate
      image and true stereographic vision is achieved. While the system requires very
      expensive hardware, it solves some of the more important problems mentioned
      above, such as the capacity to use higher frame rates and the ability to display
      images to a large audience. Mednet has instigated a research project which uses
      reconstructed models from the central nervous system (human brain and basal
      ganglia, cortex, dendrites and dendritic spines) and peripheral nervous system
      (nodes of Ranvier and axoplasmic areas). The aim is to modify the models to fit
      the different visualization techniques mentioned above and compare a group of
      users perceived degree of 3D for each technique.

PMID- 11317786
TI  - Decision support system for medical triage.
AB  - The paper explains the application of an artificial intelligence tool for the
      purpose of medical decision-making. The first product of this application is a
      triage engine, available on the Internet, to help laypersons make a decision
      about the urgency of their situation by providing tailored and accurate
      information. The expansion of this tool can lead to diagnostic tools for
      professionals or for educational purposes.

PMID- 11317787
TI  - Comparison of tracking techniques for intraoperative presentation of medical data
      using a see-through head-mounted display.
AB  - Tracking of a see-through head-mounted display is a necessary precondition for
      proper overlay of virtual data and real scenes within the display. In our
      contribution, the intention and technique for Intraoperative Presentation will be
      presented. Focus will be the tracking of the display device. We will illustrate
      and compare three different optical tracking approaches and the results achieved
      by using them.

PMID- 11317788
TI  - A new concept for intraoperative matching of 3D ultrasound and CT.
AB  - Matching of ultrasound images with CT or MRI scans is an awkward and
      unsatisfactory task when using conventional methods. Wide ranging differences in
      modality of ultrasound and CT/MRI require new techniques to be explored for
      successful alignment. Ultrasound images characteristically show comparable high
      noise ratio due to scattering inside the region of interest and the surrounding
      area. Additionally, shadowing and tissue dependent echo response time produce
      geometric artifacts. These image distortions are sophisticated to recover. Though
      image quality and geometric relationship are poor, ultrasound images show the
      potential for fast, low-cost, non-invasive and flexible image acquisition,
      predestinated for intraoperative application. The fusion of intraoperative
      ultrasound and preoperatively acquired CT/MRI images provides both, geometric
      invariance and flexible fast image acquisition, merging in a powerful tool for
      augmented three dimensional reality. In this paper we describe a completely new
      concept for alignment with abstaining from direct rigid or elastic matching of
      ultrasound to CT/MRI. Instead of placing those images in direct relationship, our
      approach involves a simulation of ultrasound wave behavior in order to predict B
      mode images.

PMID- 11317789
TI  - Human perception of haptic information in minimal access surgery tools for use in
      simulation.
AB  - This paper describes research on human perception of haptic information in
      minimal access surgery (MAS) instruments, for use in a MAS simulator.
      Understanding the thresholds of human perception is important in determining
      which haptic information must be provided for realistic feedback and which
      information can be ignored without compromising the immersive quality of the
      simulator. Initially this research has determined the limits of perception for
      non-continuous change of force amplitude and frequency in a scissors-grasping
      position.

PMID- 11317790
TI  - Design and construction of a computer-based logical system for medical diagnosis.

PMID- 11317791
TI  - Real-time simulation of dynamically deformable finite element models using modal
      analysis and spectral Lanczos decomposition methods.

PMID- 11317792
TI  - Surgical trainee assessment using a VE knee arthroscopy training system (VE
      KATS): experimental results.
AB  - Previous work has described the development of a Virtual Environment Knee
      Arthroscopy Training System (VE-KATS): a collaborative project between the
      Orthopaedic Department, Hull and East Yorkshire Hospitals NHS Trust, Hull, U.K.,
      and the Department of Computer Science, University of Hull, U.K. This work
      describes the initial results obtained by Orthopaedic Surgical Trainees using VE
      KATS. The results showed that differences between individual trainees could be
      measured using the scoring system incorporated within VE-KATS. There was a weak
      correlation with the seniority of the surgical trainees.

PMID- 11317793
TI  - Haptic palpation of head and neck cancer patients--implication for education and
      telemedicine.
AB  - Malignancy in the head and neck area is a disease that often gives high morbidity
      in functions like speech, eating, breathing and cosmetics. To ensure a treatment
      of high clinical standard these patients are presented for a multidisciplinary
      tumor-team at Sahlgren University hospital. The team usually involves ENT
      surgeons (Ear, Nose and Throat), oncologists, radiologists, pathologists, plastic
      surgeon, general surgeon and oral surgeons. The aim of the presentation is to
      classificate the tumor and suggests a treatment. The patients presented are from
      the whole western region of Sweden, and therefore some patients have to travel
      long distances. To minimize travel telemedicine was introduced 1998 with success
      [1]. One concern, when presenting a patient with telemedicine, has been the lack
      of possibility to palpate the tumor and the tissue surrounding it. To address
      this problem a 3D model of the tumor visualizes the region and possibly allows
      haptic palpation. Based on a series of high resolution CT/MR scans, a model of
      the region around the patients tumor is created. Haptic properties are added to
      the skin and subcutaneous structures (including the tumor) of the model.
      Initially, the haptic tuning is done by an examining physician, but in the final
      telemedical application, the aim is to develop a sensory device for this purpose
      (e.g. a position sensitive glove, such as Virtual Technologies, Inc. CyberGlove
      [2] and a graded system for setting firmness of the tissue). The model with its
      haptic properties can then be examined visually and haptically, the latter using
      a haptic device such as the SensAble PHANToM [3]. The present system uses a 3D
      model in VRML format based on reconstructed structures in the ROI (which includes
      the jawbones, the vertebra, the throat, major muscles and the skin) from high
      resolution CT. Haptic properties are added using MAGMA 2.5 (ReachIn Technologies
      AB, Sweden) [4]. Haptic force feedback is provided using a PHANToM Desktop
      (SensAble Technologies Inc) [3]. Visual feedback can be either monoscopic or
      stereoscopic (StereoGraphic CrystalEyes) [5]. The system will be used for concept
      testing and for evaluating possible limitations and/or the need for a modified
      examination protocol. Once a reliable set of parameters has been generated (using
      both professionals and medical students at various levels), the remote components
      will be added.

PMID- 11317794
TI  - Collaborated surgical works (surgical planning) in virtual space with tactile
      sensation between Japan and Germany.
AB  - Surgeons in Japan and Germany applied tele-virtual surgery and a force feedback
      device during a hepatectomy simulation. Using this system, surgeons in each
      country were able to perform various surgical maneuvers upon the same patient.
      They palpated abdominal skin, made electrical scalpel incisions and widened the
      incision line by using surgical tools in virtual space. While surgeons performed
      a virtual operation, the force feedback device conveyed tactile sensations. In
      each location, the force feedback devices and two graphic workstations of equal
      capability were employed. As each workstation communicated only event signals
      through an ISDN (64 Kb) line, it was possible to obtain real time tele-virtual
      surgery without a large capacity communication infrastructure.

PMID- 11317795
TI  - Web-based educational tool for cleft lip repair using XVL.
AB  - Recent web-based technologies have brought a variety of new possibilities to the
      field of medical information. Nevertheless, transferring 3D patient models
      through usual low-band-width networks is difficult because of the large size of
      data file. XVL (eXtensive VRML with Lattice), a new framework for 3D Data
      representation with high quality surface shape, has solved this problem. In
      cooperation with Lattice Technology Inc., we have created XVL-formatted patient
      3D models. The XVL model takes less than 100 kilobytes, whereas the same quality
      model in Virtual Reality Modeling Language(VRML) format requires more than 5
      megabytes. Because of the many advantages of XVL, we have created a 3D web-based
      educational tool for repair of cleft lip--plastic surgery for congenital defects
      of the lips that requires complex incisions and reconstruction. Our system can
      interact with the model and 3D visualization of the incision lines, displacement
      of skin flaps, and suturing. Our educational tool for cleft lip repair has
      demonstrated that the XVL model and its web-based application can open up new
      possibilities for 3D medical information systems. We are currently refining the
      XVL model and developing XVL-based applications to simulate the actual surgery on
      the World Wide Web.

PMID- 11317796
TI  - Keeping sharp: Internet CE update and experience.
AB  - The Internet as a distance-learning tool is evolving rapidly. Most Internet-based
      Continuing Education (CE) experiences follow a standard didactic approach as
      demonstrated by lectures, slide presentations, written journals, videotape, and
      audiotape; however, some Internet-based educators are exploring the full
      interactive, problem-solving potential of Internet technology. With support from
      NIMH we are reviewing the state of the art in Internet-based CE and developing CE
      courses targeted toward primary care providers that aim to alter clinical skills
      related to depression treatment.

PMID- 11317797
TI  - Using virtual reality to teach special populations how to cope in crisis: the
      case of a virtual earthquake.
AB  - The unique characteristics of special populations such as pre-school children and
      Down syndrome kids in crisis and their distorted self-image were never studied
      before, because of the difficulty of crisis reproduction. This study proposes a
      VR setting that tries to model some special population's behaviour in the time of
      crises and offers them a training scenario. The sample population consisted of 30
      pre-school children and 20 children with Down syndrome. The VR setting involved a
      high-speed PC, a VPL EyePhone 1, a MR toolkit, a vibrations plate, a motion
      capture system and other sensors. The system measured and modelled the typical
      behaviour of these special populations in a Virtual Earthquake scenario with
      sight and sound and calculated a VR anthropomorphic model that reproduced their
      behaviour and emotional state. Afterwards one group received an emotionally
      enhanced VR self-image as feedback for their training, one group received a plain
      VR self-image and another group received verbal instructions. The findings
      strongly suggest that the training was a lot more biased by the emotionally
      enhanced VR self-image than the other approaches. These findings could highlight
      the special role of the self-image to therapy and training and the interesting
      role of imagination to emotions, motives and learning. Further studies could be
      done with various scenarios in order to measure the best-biased behaviour and
      establish the most natural and affective VR model. This presentation is going to
      highlight the main findings and some theories behind them.

PMID- 11317798
TI  - 3-D simulation of craniofacial surgical procedures.
AB  - An integrated system for simulating craniofacial surgical procedures is
      presented. The system computes nonlinear soft-tissue deformation due to bone
      realignment. It is capable of simulating bone cutting and bone realignment with
      integrated interactive collision detection. Furthermore, soft-tissue deformation
      and cutting due to surgical instruments can be visualized. The system has been
      tested with several individual patient data sets. Simulation processes are based
      on a 3-D model of a patient's preoperative bone structure of the skull derived
      from a computer tomography scan and on a 3-D, photorealistic model of the
      patient's preoperative appearance obtained by a laser range scanner. The multi
      layer soft-tissue model is represented by nonlinear springs. Very fast and robust
      prediction of nonlinear soft-tissue deformation is computed by optimizing a
      nonlinear cost function.

PMID- 11317799
TI  - A medical platform for simulation of surgical procedures.
AB  - Surgery simulation is a promising technique for training of surgical procedures.
      The overall goal for any surgical simulator is to allow for efficient training of
      the skills required and to improve learning by giving the user proper feedback.
      This goal is easier achieved if the training is performed in a realistic
      environment. Therefore functionality such as soft tissue deformation, tearing and
      cutting, penetration of soft tissue etc. is necessary. Furthermore, a realistic
      simulator must provide haptic feedback so that all senses match, that is, there
      should be a correspondence between what you see and what you feel with your
      hands. In this paper we describe a medical platform that provides all this
      functionality. It is based on the Reachln Magma API, which has been extended for
      surgery simulation. We describe the development of the platform and illustrate
      the use of it for the development of two different types of surgical simulators,
      both of which represents work in progress.

PMID- 11317800
TI  - Clinical validation of computer assisted pelvic surgery using ultrasound. A
      percutaneous safe technique with low radiation exposure.
AB  - This study presents early results of the clinical experience of computer assisted
      surgery (CAS) applied to percutaneous iliosacral screwing. The results of these
      10 first cases (4 patients) are compared to an historical series of 51 cases (30
      patients). The CAS technique shows better screw placement without outside bone
      screw and a very low radiation exposure.

PMID- 11317801
TI  - The interaction of spatial ability and motor learning in the transfer of training
      from a simulator to a real task.
AB  - Virtual Reality (VR) based simulators have been used as a training tool in many
      settings, although very few studies examine transfer of training from simulators
      to a real world task, particularly for manipulation tasks. Simulators could play
      a key role as an enabling technology for manipulation tasks related to
      teleoperation, and medical procedure training. We investigated the relationship
      between motor tasks and participants' spatial abilities. This relationship was
      further examined with respect to learning in a simulator and to transfer of
      training from the simulator to the real world on a pick-and-place task. Spatial
      abilities were characterized using a battery of recognition and manipulation
      figural tests. Subjects with lower spatial abilities demonstrated significant
      positive transfer from a simulator based training task to a similar real world
      robotic operation task. Subjects with higher spatial skills did not respond as
      positively from training in a simulated environment.

PMID- 11317802
TI  - An enabling system for echocardiography providing adaptive support through
      behavioral analysis.
AB  - Echocardiography requires the integrated application of a broad spectrum of
      cognitive and practical skills, e.g. diagnostic knowledge (symbolic), image
      interpretation (visual perception) and handling of the ultrasound probe
      (sensorimotor). This complex expertise is acquired through extensive practical
      training guided by a skilled cardiologist that is often incompatible with
      clinical reality. Especially for beginners, the most critical point during an
      echocardiographic examination is the steering of the ultrasound probe to navigate
      between different cardiological standard planes (sensorimotor skill) without
      loosing orientation. These transitions or "standard trajectories" can roughly be
      described by specific movement patterns. We propose an enabling system based on
      an Augmented Reality simulator for two-dimensional echocardiography imitating
      this apprenticeship [1]-[3]. During a simulated ultrasound examination the system
      monitors the activities of the trainee and analyzes the motion pattern of the
      ultrasound probe. The simulator reacts by mapping the motion patterns onto
      cognitive orientation demands and providing adaptive feedback in the form of
      context sensitive help (animations). It partly takes the role of the critical
      teacher.

PMID- 11317803
TI  - Stereoscopic x-ray image processing.
AB  - A three-step stereoscopic image-processing algorithm is proposed in order to
      improve image quality and depth perception of stereoscopic radiographs taken with
      C-arm equipment. The steps include illumination correction, geometry conversion
      and screen parallax adjustment. Flipping of stereoscopic radiographs is also
      discussed.

PMID- 11317804
TI  - The development of an evaluation framework for the quantitative assessment of
      computer-assisted surgery and augmented reality accuracy performance.
AB  - The paper describes a framework for the quantitative assessment of errors within
      a computer assisted surgical system. The framework diagrammatically describes the
      registration process and simulates the error propagation chain based on the
      assumption that errors can be described through the use of a normal distribution
      model. The projection error associated with a fluoroscopic image intensifier is
      given as an example.

PMID- 11317805
TI  - 3D registration through pseudo x-ray image generation.
AB  - Registration of a pre operative plan with the intra operative position of the
      patient is still a largely unsolved problem. Current techniques generally require
      fiducials, either artificial or anatomic, to achieve the registration solution.
      Invariably these fiducials require implantation and/or direct digitisation. The
      technique described in this paper requires no digitisation or implantation of
      fiducials, but instead relies on the shape and form of the anatomy through a
      fully automated image comparison process. A pseudo image, generated from a
      virtual image intensifier's view of a CT dataset, is intra operatively compared
      with a real x-ray image. The principle is to align the virtual with the real
      image intensifier. The technique is an extension to the work undertaken by
      Domergue [1] and based on original ideas by Weese [4].

PMID- 11317806
TI  - A VR-based multicomponent treatment for panic disorders with agoraphobia.
AB  - Agoraphobia consists of a group of fears of public places such as going outside,
      using public transportation and being in public places, which cause serious
      interference in daily life. Many studies demonstrated the effectiveness of a
      multicomponent cognitive-behavioral treatment strategy for panic disorder with
      agoraphobia. The traditional protocol involves a mixture of cognitive and
      behavioral techniques which are intended to help patients identify and modify
      their dysfunctional anxiety-related thoughts, beliefs and behavior. Emphasis is
      placed on reversing the maintaining factors identified in the cognitive and
      behavioral patterns. We use Virtual Reality (VR) to support Panic Disorder
      treatment. The preliminary treatment protocol for Panic Disorder and Agoraphobia,
      named Experiential-Cognitive Therapy (ECT), was developed at the Applied
      Technology for Neuro-Psychology Lab of Istituto Auxologico Italiano, Verbania,
      Italy, in cooperation with the Psychology Department of the Catholic University
      of Milan, Italy. The actual version included the efforts of researchers from the
      Center for Advanced Multimedia Psychotherapy, California School of Professional
      Psychology, San Diego (CA), USA, and from the Seoul Paik Hospital, Inje
      University, Seoul, Korea. The goal of ECT is to decondition fear reactions, to
      modify misinterpretational cognition related to panic symptoms and to reduce
      anxiety symptoms. The characteristics of the approach will be presented through
      the description of the clinical protocol.

PMID- 11317807
TI  - Virtual reality as clinical tool: immersion and three-dimensionality in the
      relationship between patient and therapist.
AB  - VR represents the maximum level of evolution in interaction between man and
      computer systems. In Clinical Psychology, the virtual cyberspace offers a series
      of powerful and valid applications for diagnosis and therapy. The qualities that
      make VR software reliable and particularly useful in the practice of assessment
      and rehabilitation of certain psychopathological dysfunctions emerge with extreme
      clarity from the specialist literature. VR constitutes a three-dimensional
      interface that puts the interacting subject in a condition of active exchange
      with a world re-created via the computer. The possibility of not limiting the
      paradigm of interaction in a unidirectional sense represents the strong point of
      the new technology: man is not simply an external observer of pictures or one who
      passively experiences the reality created by the computer, but on the contrary
      may actively modify the three-dimensional world in which he is acting, in a
      condition of complete sensorial immersion. The nature of this exchange means that
      the subject feels actually present in this new context. The feeling of "actual
      presence" is perhaps the peculiar characteristic of this tool and is made
      possible both by the realistic reproduction of the cybernetic environments and by
      the involvement of all the sensorimotor channels during interaction. In this
      paper we focus on the characteristics of the new configuration in the
      relationship between patient and therapist.

PMID- 11317808
TI  - The VIBE of the burning agents: simulation and modeling of burns and their
      treatment using agent-based programming, virtual reality, and human patient
      simulation.

PMID- 11317809
TI  - ICAPS an integrative computer-assisted planning system for pedicle screw
      insertion.
AB  - Robot Assisted Surgery (RAS) Systems win more and more recognition in the field
      of orthopaedics. Especially in Hip Surgery RAS has proved to be suited for
      application in medical routine. Often Robot Assisted Surgery Systems consist of a
      planning- and an interoperative component. According to specifications done with
      the planning software the tools are driven. Benefits of the robot assisted
      surgery should be higher precision and a better surgical outcome. In the co
      operation project of several Fraunhofer Institutes "RoMed" (Robots and
      Manipulators for Medical Application) an exemplary application of robot aided
      spine surgery is developed [1]. The planning software used in this context is
      proposed in this article.

PMID- 11317810
TI  - Psychometric properties of the driVR: a virtual reality driving assessment.
AB  - This study provides data on the psychometric properties of the driVR, a virtual
      reality assessment used to assess driving in persons with brain injury. Several
      driVR measures were compared to other established indicators of driving
      performance. Many concurrent validity coefficients over r = 0.3 were identified
      between driVR measures of lane tracking with on-road, Trail Making Test, and the
      Driver Performance Test II scores. The results provide further evidence to
      support the concurrent validity of the driVR. Continued research addressing other
      aspects of validity and reliability is recommended.

PMID- 11317811
TI  - A prototype haptic suturing simulator.
AB  - A new haptic simulation designed to teach basic suturing for simple wound closure
      is described. Needle holders are attached to the haptic device as the graphics of
      the needle holders, needle, sutures and virtual skin are displayed and updated in
      real time. The simulator incorporates several interesting components such as real
      time modeling of deformable skin, tissue and suture material and real-time
      recording of state of activity during the task using a finite state model.

PMID- 11317812
TI  - An efficient method for modelling soft tissue in virtual environment training
      systems.
AB  - Modelling soft tissues in virtual environment training systems is frequently
      required. The provision of both visually compelling and physically accurate
      models presents a number of problems for the developer. The Finite element
      technique presented in this paper, modal analysis, can be programmed to allow the
      user to easily trade-off accuracy of simulation for execution speed. It has been
      successfully used to produce simulations of the lateral meniscus on low powered
      portable computer systems.

PMID- 11317813
TI  - Immersive virtual reality used as a platform for perioperative training for
      surgical residents.
AB  - Perioperative preparations such as operating room setup, patient and equipment
      positioning, and operating port placement are essential to operative success in
      minimally invasive surgery. We developed an immersive virtual reality-based
      training system (REMIS) to provide residents (and other health professionals)
      with training and evaluation in these perioperative skills. Our program uses the
      qualities of immersive VR that are available today for inclusion in an ongoing
      training curriculum for surgical residents. The current application consists of a
      primary platform for patient positioning for a laparoscopic cholecystectomy.
      Having completed this module we can create many different simulated problems for
      other procedures. As a part of the simulation, we have devised a computer-driven
      real-time data collection system to help us in evaluating trainees and providing
      feedback during the simulation. The REMIS program trains and evaluates surgical
      residents and obviates the need to use expensive operating room and surgeon time.
      It also allows residents to train based on their schedule and does not put
      patients at increased risk. The method is standardized, allows for repetition if
      needed, evaluates individual performance, provides the possible complications of
      incorrect choices, provides training in 3-D environment, and has the capability
      of being used for various scenarios and professions.

PMID- 11317814
TI  - Anatomical accuracy in medical 3D modeling.
AB  - In complex surgery, medical modeling has become an accepted tool for diagnosis,
      simulation and the planning of surgical interventions [1]. However, the question
      concerning the accuracy of the model, i.e. the equivalence between the model
      itself on the one hand and the original anatomical situation on the other hand,
      remains unanswererd in the current literature.

PMID- 11317815
TI  - Reconstructing hierarchical tetrahedral mesh density models of bony anatomy.
AB  - We proposed an efficient and automatic method to reconstruct hierarchical
      tetrahedral meshes and build density models for bony anatomy from CT data sets.
      The mesh is reconstructed from contours extracted in CT images corresponding to
      the outer bone surfaces and the boundaries between compact bone, spongy bone and
      medullary cavity. Key problems, such as tiling problem, branching problem,
      correspondence problem, and constraint problem, have been solved. We then
      approximated bone density variations by means of continuous density functions in
      each tetrahedron. The density functions are written as smooth Bernstein
      polynomial spline expressed in terms of barycentric coordinates associated with
      each tetrahedron. We further performed the tetrahedral mesh simplification by
      edge collapsing and built hierarchical structure of multiple resolution meshes.
      We applied our density model to efficiently generate Digitally Reconstructed
      Radiographs. This research is part of our effort to build a bone density atlas.

PMID- 11317816
TI  - Anatomic modeling from unstructured samples using variational implicit surfaces.
AB  - We describe the use of variational implicit surfaces (level sets of an embedded
      generating function modeled using radial basis interpolants) in anatomic
      modeling. This technique allows the practitioner to employ sparsely and unevenly
      sampled data to represent complex biological surfaces, including data acquired as
      a series of non-parallel image slices. The method inherently accommodates
      interpolation across irregular spans. In addition, shapes with arbitrary topology
      are easily represented without interpolation or aliasing errors arising from
      discrete sampling. To demonstrate the medical use of variational implicit
      surfaces, we present the reconstruction of the inner surfaces of blood vessels
      from a series of endovascular ultrasound images.

PMID- 11317817
TI  - Issues in validation of a dermatologic surgery simulator.
AB  - At the University of Washington, we have been developing a suturing simulator
      using novel finite element model techniques which allow real-time haptic
      feedback. The issues involved in measuring validity in a suturing model have not
      been examined in a systematic way. Very few studies exist on the surgical factors
      that lead to good sutures. We have examined published data on these factors as
      well as previously studied metrics in suture training. This information has been
      combined with a review of types of validity (e.g., face, construct, predictive
      and concurrent) and reliability that must be considered in assessing any surgical
      simulator.

PMID- 11317818
TI  - Intelligent system and risk of different diseases in the general population.
AB  - This is a new approach to define the risk of the general population for a
      specific disease. We use Bayesian theory to define the risk of the population.
      Analyzing the major risk factors of a disease, how they affect the incidence
      and/or prevalence of the disease, and the statistics of each risk factor in the
      population, along with the power of the Bayes theorem helps us define the risk of
      that population for that disease. To find out what the risk of the general
      population for a disease is, prospective epidemiological studies in the
      population shown are needed. These studies usually lead to the identification of
      the major risk factors for a disease and their impacts which are quite costly and
      requires a long time to get to the results. Also a large personnel is needed to
      perform effectively in the study. The result of the risk of the general
      population for a first heart attack using our software is in agreement with the
      result of the Framingham heart study. Large studies like Framingham is not
      available for other diseases to enable us to evaluate the accuracy of our
      software precisely. To overcome this shortage we have sought medical experts'
      evaluation of the predicted risk of the general population for other disease by
      this software, which needs to be completed.

PMID- 11317819
TI  - Software framework for a surgical guidance system using magnetic markers.
AB  - Use of active, optical tracking Surgical Guidance systems provides line of sight
      problems to the surgeon. We plan to use a new magnetic system, 'Aurora' from
      Northern Digital Inc. (Canada) and Mednetix AG (Switzerland), in intra-operative
      fluoroscopy to develop an integrated system for surgical guidance. Here we
      outline the modules developed for use with this system, including a novel
      registration method.

PMID- 11317820
TI  - Measuring in vivo animal soft tissue properties for haptic modeling in surgical
      simulation.
AB  - To provide data for the design of virtual environments and teleoperated systems
      for surgery, it is necessary to measure tissue properties under both in vivo and
      ex vivo conditions. The former provides information about tissue behavior in its
      physiological state, while the latter can provide better control over
      experimental conditions. We have developed devices to measure tissue properties
      under extension and indentation, as well as to record instrument-tissue
      interaction forces. We are creating a web database of data recorded from porcine
      abdominal tissues.

PMID- 11317821
TI  - A virtual environment for simulated rat dissection.
AB  - Animal dissection for the scientific examination of organ subsystems is a
      delicate procedure. Performing this procedure under the complex environment of
      microgravity presents additional challenges because of the limited training
      opportunities available that can recreate the altered gravity environment.
      Traditional crew training often occurs several months in advance of
      experimentation, provides limited realism, and involves complicated logistics. We
      have developed an interactive virtual environment that can simulate several
      common tasks performed during animal dissection. In this paper, we describe the
      imaging modality used to reconstruct the rat in virtual space, provide an
      overview of the simulation environment and briefly discuss some of the techniques
      used to manipulate the virtual rat.

PMID- 11317822
TI  - Neuronavigational epilepsy focus mapping.
AB  - The localization of a seizure focus for resective surgery often requires invasive
      monitoring for precise localization of the target as well as structures to avoid.
      We report on the use of intra-operative surgical navigation to precisely localize
      and co-register subdural electrodes to regions of know radiographic pathology.
      Additionally, the navigation system was used to develop intra-operative electrode
      maps. These maps were subsequently used in the sub-acute recording phase to
      assign electrographic pathology and function (e.g. speech) to a specific cortical
      surface anatomy. This permitted for more precise planning of surgery and better
      assessment of potential risk, based on functional as well as anatomical
      criterion.

PMID- 11317823
TI  - Safety in computer assisted surgery.
AB  - Today, surgeons accept computer assisted technologies as important tools to
      enhance the treatment of a patient. The positive impact and acceptance of
      computer assisted technologies could be increased to a great extent, if all
      methods and devices used for diagnosis and treatment of a patient are better co
      ordinated and more finely tuned. Often computer assisted treatments cannot be
      performed due to a lack of communication between hospital departments, useless
      patient data, deficient interfaces, etc. Risks for the patient and potential
      errors within the treatment are often unrecognised, as up to now the safety of
      computer integrated surgery is only product-, device and security oriented. We
      have developed a new approach for a safety architecture, which includes safety
      aspects considering patients, users, interdependencies and interactions of
      computer assisted methods and apparatuses.

PMID- 11317824
TI  - The Virtual Anatomy Lab: a hands-on anatomy learning environment.
AB  - This paper introduces the Virtual Anatomy Lab software platform for coordinating
      on-line gross anatomy learning sessions over time.

PMID- 11317825
TI  - Telesonography: technical problems, solutions and results in the routine
      utilization from remote areas.

PMID- 11317826
TI  - Autocolorization of three-dimensional radiological data.
AB  - It requires skill, effort, and time to visualize desired anatomic structures from
      radiological data in three-dimensions. There have been many attempts at
      automating this process and making it less labor intensive. The technique we have
      developed is based on mutual information for automatic multi-modality image
      fusion (MIAMI Fuse, University of Michigan). The initial development of our
      technique has focused on the autocolorization of the liver, portal vein, and
      hepatic vein. A standard dataset in which these structures had been segmented and
      assigned colors was created from the full color Visible Human Female (VHF) and
      then optimally fused to the fresh CT Visible Human Female. This semi-automatic
      segmentation and coloring of the CT dataset was subjectively evaluated to be
      reasonably accurate. The transformation could be viewed interactively on the
      ImmersaDesk, in an immersive Virtual Reality (VR) environment. This 3D
      segmentation and visualization method marks the first step to a broader,
      standardized automatic structure visualization method for radiological data. Such
      a method, would permit segmentation of radiological data by canonical structure
      information and not just from the data's intrinsic dynamic range.

PMID- 11317827
TI  - Development and evaluation of an epidural injection simulator with force feedback
      for medical training.
AB  - Performing epidural injections is a complex task that demands a high level of
      skill and precision from the physician, since an improperly performed procedure
      can result in serious complications for the patient. The objective of our project
      is to create an epidural injection simulator for medical training and education
      that provides the user with realistic feel encountered during an actual
      procedure. We have used a Phantom haptic interface by SensAble Technologies,
      which is capable of three-dimensional force feedback, to simulate interactions
      between the needle and bones or tissues. An additional degree-of-freedom through
      an actual syringe was incorporated to simulate the "loss of resistance" effect,
      commonly considered to be the most reliable method for identifying the epidural
      space during an injection procedure. The simulator also includes a new training
      feature called "Haptic Guidance" that allows the user to follow a previously
      recorded expert procedure and feel the encountered forces. Evaluations of the
      simulator by experienced professionals indicate that the simulation system has
      considerable potential to become a useful aid in medical training.

PMID- 11317828
TI  - Biointelligence age: implications for the future of medicine.

PMID- 11317830
TI  - Safety and efficacy of Eupatorium laevigatum paste as therapy for buccal aphthae:
      randomized, double-blind comparison with triamcinolone 0.1% orabase.
AB  - Eupatorium laevigatum Lam. is a plant common to the central region of Brazil,
      where it is a widely used remedy for lesions such as buccal aphthae. These
      painful inflammatory ulcers affect 50% of the general population. For the first
      part of this two-part study, a phytotherapeutic preparation from E. laevigatum
      extracts was formulated into an orabase paste appropriate for use on the buccal
      mucosa. The study evaluated the toxicologic safety of this paste in 20 healthy
      volunteers, as determined by changes in biochemical and hematologic values and on
      urinalysis and intrabuccal examination. The second part of the study was a
      randomized, double-blind comparison of efficacy with triamcinolone 0.1% orabase
      in 60 patients. The healthy volunteers tolerated the phytotherapeutic paste well,
      and no adverse effects could be attributed to its use. In the clinical
      comparison, after 5 days of treatment, 40% of the patients who used the paste and
      26.7% of those who used triamcinolone obtained complete cure of the ulcers. Pain
      was alleviated in 70% of the phytotherapeutic group and in 33.3% of the
      triamcinolone group. The phytotherapeutic paste of E. laevigatum was a safe and
      effective treatment of buccal aphthae, the most common disease of the buccal
      mucosa.

PMID- 11317829
TI  - Multicenter evaluation of the efficacy and safety of gatifloxacin in Mexican
      adult outpatients with respiratory tract infections.
AB  - Respiratory tract infections (RTIs), the most common indication for outpatient
      antimicrobial therapy, impose a heavy medical and societal burden and present a
      difficult therapeutic challenge in the face of increasing pathogen resistance
      worldwide. Gatifloxacin is a new broad-spectrum fluoroquinolone with excellent
      activity against prevalent respiratory bacteria, including penicillin-resistant
      Streptococcus pneumoniae and atypical pathogens. A multicenter, open-label,
      noncomparative surveillance study carried out in Mexico evaluated the safety and
      efficacy of oral gatifloxacin 400 mg once daily in 17,923 adult outpatients with
      community-acquired pneumonia (CAP) (n = 3322), acute exacerbations of chronic
      bronchitis (AECB) (n = 5885), and acute bacterial sinusitis (n = 8716).
      Voluntary, unpaid physician participation contributed to an unbiased study
      design. Physician-assessed global rate of cure or improvement was 96.3%; efficacy
      was 95.8% in CAP, 96.1% in AECB, and 96.4% in sinusitis. The incidences of
      relapse (1.5%) and therapeutic failure (0.7%) were low. The most commonly
      reported adverse events, nausea (2.76%), headache (2.20%), and dizziness (1.33%),
      were generally mild and self-limited. Oral gatifloxacin 400 mg once daily is
      effective and safe for patients with CAP, AECB, and acute sinusitis.

PMID- 11317831
TI  - An easy-to-use dry-powder inhaler.
AB  - The mometasone furoate dry-powder inhaler is a novel device designed to support
      compliance by delivering a topical corticosteroid in a simple three-step
      operation. This breath-actuated inhaler uses a stabilized agglomerate formulation
      to measure and deliver accurate, uniform, and precise doses of drug over a range
      of inspiratory flow rates. Laboratory and clinical data have shown that the
      design produced a simple, clinically effective inhaler for the treatment of
      adults and children 12 years of age and older with mild, moderate, or severe
      persistent asthma.

PMID- 11317833
TI  - Novel material properties via ionising radiation.
AB  - Ionising radiation is normally associated with the degradation of materials
      during radiation sterilisation. However, these same radiation sources can be used
      to create material properties that are unobtainable by other methods. This review
      of some novel properties that can be achieved also critically compares the
      relative merits and disadvantages of each radiation source.

PMID- 11317832
TI  - A comparison of two phase III multicenter, placebo-controlled studies of
      tamsulosin in BPH.
AB  - In two large, multicenter, double-blind, parallel, US phase III clinical trials,
      men with benign prostatic hyperplasia were randomized to receive tamsulosin,
      either 0.4 or 0.8 mg daily, or placebo for 13 weeks. Efficacy was determined by
      changes from baseline in American Urological Association (AUA) symptom scores and
      peak urinary flow and by percentages of responders with clinically meaningful (>
      25%) AUA score improvement and at least 30% increase in peak urinary flow.
      Secondary efficacy parameters were AUA and Boyarsky irritative, obstructive, and
      individual scores; investigators' global assessment; and a total quality-of-life
      evaluation. Also analyzed were laboratory test results and adverse events,
      including orthostatic and antihypertensive effects. A trend toward statistically
      significant improvement occurred in all primary and secondary efficacy endpoints
      at both dosages versus placebo, except for peak urinary flow rate at endpoint in
      one trial with 0.4 mg of tamsulosin (P = .064). Urinary flow rates increased
      within hours after first tamsulosin dose. No clinically or statistically
      meaningful sitting blood pressure or symptomatic orthostatic changes were seen,
      and no physical findings or alterations in laboratory or electrocardiographic
      results were attributable to treatment. Tamsulosin 0.4 and 0.8 mg daily had a
      rapid onset of action and was effective and well tolerated, with minimal
      differences observed between dosage groups. The incidence of side effects was
      similar to that with placebo, and efficacy was sustained with 0.4 mg daily.

PMID- 11317834
TI  - Sterilisation technology choices during. Product design and development.
AB  - Sterilisation is a critical and integral stage in the manufacture of a sterile
      device. It should, therefore, be recognised at the design stage of the device if
      the desired confidence in the end product and potential benefits of sterilisation
      options are to be achieved. This article highlights some of the issues to
      consider when selecting the most appropriate sterilisation method.

PMID- 11317835
TI  - The technological edge.

PMID- 11317836
TI  - Nurturing your intellectual property.
AB  - The Internet is providing an alternative way for companies to harness the
      potential of their intellectual property and gain a steady new revenue stream in
      often unexpected areas.

PMID- 11317837
TI  - Selecting a sterilisation subcontractor.
AB  - Medical device manufacturers who need contract sterilisation services sometimes
      lack extensive knowledge of the technical aspects of sterilisation processes. For
      this reason, they may have problems assessing quality requirements for
      subcontractor sterilisation services. This article discusses important quality
      issues that should be considered when selecting a sterilisation subcontractor.

PMID- 11317838
TI  - Standards in the 21st century. Quality questions.

PMID- 11317839
TI  - Denmark. Information supplied by the Danish Medical Device Association.

PMID- 11317840
TI  - Norway. The high spender.

PMID- 11317841
TI  - Sweden. Looking for cost efficiency.

PMID- 11317842
TI  - Finland. The great importer.

PMID- 11317843
TI  - Obtaining small parts with micromachining.
AB  - Microengineering techniques now deliver much smaller products with increased
      accuracy and cost-effectiveness. This article looks at the opportunities offered
      by today's micromachining methods.

PMID- 11317845
TI  - How to stop hemorrhaging red ink.

PMID- 11317844
TI  - From sterile debate to burning issue: the economics and safety dichotomy.
AB  - Surgical instruments are thought to be capable of transmitting spongiform
      encephalopathies from patient to patient, even after sterilisation. At the same
      time, there is an increasing trend to reuse devices intended for single use. This
      article discusses certain aspects of that apparent contradiction.

PMID- 11317846
TI  - Electronic medical records: 10 questions I didn't know to ask.

PMID- 11317847
TI  - Tips to help take the hassle out of inpatient utilization review.

PMID- 11317848
TI  - Complementary and alternative medicine: a primer.

PMID- 11317849
TI  - What you need to know about HIPAA now.

PMID- 11317850
TI  - Focus on the family, Part I: What is your family focus style?

PMID- 11317851
TI  - Getting more from a voice recognition system.

PMID- 11317852
TI  - Healing bodies and souls.

PMID- 11317853
TI  - New year, new codes: highlights from CPT and HCPCS 2001.

PMID- 11317854
TI  - Is quality of care getting more difficult to provide?

PMID- 11317855
TI  - The future of health care financing.

PMID- 11317856
TI  - Interviewing 101.

PMID- 11317857
TI  - Seven steps to Medicare compliance.

PMID- 11317858
TI  - Electronic medical records: the FPM vendor survey.

PMID- 11317859
TI  - 13 months of quality improvement: did it work?

PMID- 11317860
TI  - Killer medical devices: the media versus the industry.
AB  - Are medical products killer devices or life-improving instruments? This issue is
      being fought out in the general media today. The first article in a new series of
      the Material Matters column discusses this unwelcome phenomenon and examines the
      arguments.

PMID- 11317861
TI  - Polymers in dialysis: characteristics and needs.
AB  - Polymers employed in dialysis must always be evaluated from the perspective of
      blood compatibility. This article traces the developments that have taken place
      in biocompatibility and biostability in dialysis treatment and the mechanisms
      that are involved.

PMID- 11317862
TI  - Medical applications of microsystems technology: news update.
AB  - Medical product companies showed an increasing level of interest in microsystems
      technology (MST) during 2000. Access to MST has improved with the emergence of
      new suppliers and existing technology providers becoming more market oriented.
      Some of the highlights and details of forthcoming events are reported here.

PMID- 11317863
TI  - The technological edge.
AB  - A new monthly column featuring successful developments from the MedLINK
      Programme. This month features a new stent that has been produced using an
      embroidery technique.

PMID- 11317864
TI  - The impact of the new quality management system standards on the CE-marking
      process.
AB  - In December 2000, the new ISO 9000 quality management system series of standards
      was published. This represents a significant development for manufacturers
      marketing medical devices in Europe, who use these standards to demonstrate
      conformity to the European medical device Directives. This article discusses some
      issues related to the introduction of these standards in Europe and their use in
      the CE-marking process.

PMID- 11317865
TI  - FDA's Quality System Inspection Technique in Ireland.

PMID- 11317866
TI  - Self-preservation in the face of regulatory adversity.
AB  - Companies operating in some Member States may soon be faced with regulatory
      burdens going far beyond the requirements of the In Vitro Diagnostic Directive,
      which will result in greater costs and difficulties in marketing in vitro
      diagnostic devices. Companies can, however, use rights derived from European
      Union law to protect themselves from the commercial impact of national rules of
      this type.

PMID- 11317868
TI  - Visit the ideas factory.

PMID- 11317867
TI  - A practical guide to adhesive bonding.
AB  - Choosing the best adhesive method can be an exacting design task. This is
      especially true when joining dissimilar materials and when bonding certain
      plastics. All too often the adhesive is not fully considered at the design stage,
      which leads to problems during production. This guide discusses the key elements
      of the bonding process and provides advice when things do not go right.

PMID- 11317869
TI  - Control freaks.

PMID- 11317870
TI  - The future with the UK Medical Devices Agency.
AB  - The medical device industry is facing a period of profound change and
      opportunity. This is partly arising from rapid developments in various fields of
      science and technology and partly from sociological and perceptual changes in
      society. One regulatory agency describes how it is responding to the challenge.

PMID- 11317871
TI  - The ABHI looks deep into the future.

PMID- 11317872
TI  - The hunt for medical errors: a serious quest?

PMID- 11317873
TI  - Medical professionalism in the life insurance industry.
AB  - Steadily increasing competition has changed the underwriting environment in most
      life insurance companies. This article attempts to explore how heightened
      competition presents a new challenge for medical professionals employed in the
      industry.

PMID- 11317874
TI  - The Brugada syndrome--an electrocardiogram with important mortality implications.
AB  - The electrocardiogram (ECG) is a valuable screening tool for increased risk in
      underwriting life insurance applicants. This article discusses a recently
      described ECG pattern associated with a high risk of sudden unexpected death.

PMID- 11317875
TI  - Liver biopsy interpretation in chronic hepatitis.
AB  - Liver biopsy reports are very variable in their terminology. In this article,
      frequently used terms and 2 common scoring systems are described.

PMID- 11317876
TI  - Long-term morbidity and mortality risk in Japanese insurance applicants with
      chronic hepatitis C virus infection.
AB  - BACKGROUND: Japan has the highest rate of liver cancer of any industrialized
      country in the world, and research indicates that hepatitis C virus (HCV) is
      responsible for 50-76% of these cases. The natural history of chronic HCV
      infection is difficult to determine because the initial bout of acute infection
      is usually not recognized and serious complications generally do not develop for
      at least 3 decades. This article discusses use of a Markov model to estimate long
      term morbidity and mortality risk associated with chronic HCV infection in
      otherwise healthy Japanese insurance applicants. A range of risk estimates is
      derived based on different assumptions of disease progression. RESULTS: Data for
      this analysis were based on prospective and combined retrospective-prospective
      studies of populations infected at different ages and followed for durations of
      up to 25 years. Estimated mortality ratios varied with assumptions regarding rate
      of progression from active HCV infection to cirrhosis. For males, peak mortality
      ratios decreased with advancing age at underwriting, from a high of 253% (age 20)
      to a low of 144% (age 60). A similar age-related pattern was seen for females,
      from a peak mortality ratio of 222% (age 20) to a low of 156% (age 60). In
      contrast to the pattern of decreasing relative mortality at older ages, morbidity
      increased with age at underwriting. Sensitivity analysis indicated that
      calculations in the model were sensitive to different transition rates from
      active HCV infection to cirrhosis and from cirrhosis to HCC, but were not
      sensitive to treatment frequency and success or the percentage of people treated
      prior to application. A review of the literature also suggested that a favorable
      prognosis was likely in applicants with persistently normal ALT levels, but
      prognosis was less certain for those with intermittent or persistent elevation of
      liver enzymes. CONCLUSION: Morbidity and mortality are within the insurable range
      for the majority of HCV-infected persons. Risk varies with gender, age at
      infection, and other variables discussed in the article.

PMID- 11317877
TI  - Long-term mortality after spinal cord injury.

PMID- 11317878
TI  - Mortality outcome of surgically treated atrial septal defects.
AB  - Comparative mortality in this abstract shows that surgical repair of an atrial
      septal defect (ASD) confers a survival advantage beyond that expected for the
      study population. Determinates of expected mortality and mean q' include the
      table selected, zero-time age and annual age, and sex distribution of the cohort.
      Each has an independent effect on mortality ratios and excess death rates.
      Confounding variables such as participant selection within the study cohort
      affect the outcome. Despite the multiple, methodologic variables in this
      abstract, individuals having surgical repair of an ASD appear to have low
      mortality.

PMID- 11317879
TI  - C-reactive protein--a screening test for coronary disease?
AB  - C-reactive protein (CRP) is one of a number of substances termed "acute phase
      reactants," biologic substances that appear in the circulation when an active
      inflammatory process occurs. Although traditionally used to monitor or detect
      major infectious or inflammatory conditions, elevations of CRP levels within the
      conventional range of "normals" has been intensively studied as a marker for
      coronary disease and risk of future coronary events. Sensitive assays that can be
      performed on a high-volume, commercial basis are now available. CRP appears to be
      a valuable marker for the prediction of future events in individuals who have
      known coronary artery disease. CRP has been proposed as a coronary disease
      screening test for healthy individuals; however, available data suggest that use
      of CRP in this context may be premature. This paper reviews published research
      concerning CRP and the prediction of cardiovascular and total mortality risk,
      then outlines the current "state of the art" for the application of CRP to the
      risk assessment process.

PMID- 11317880
TI  - Incidence of seizures after traumatic brain injury--a 50-year population survey.
AB  - BACKGROUND: Records of the Rochester Epidemiological Project were used to
      determine the incidence of secondary seizures after traumatic brain injury (TBI)
      in all cases treated for this condition in the population of Olmsted County,
      Minn, from 1935 to 1984. Medical records of the Mayo Clinic and all other medical
      facilities in Olmsted County, Minn, are in the database of this Project.
      Incidence rates after TBI were compared with incidence rates of idiopathic
      epilepsy previously determined for Olmsted County. RESULTS: TBI cases were
      divided into 3 defined severity categories: mild, moderate, and severe. Out of
      4541 cases of TBI accumulated in 50 years only 97 cases developed 1 or more
      seizures (46 cases of seizure secondary to other definite causes were excluded).
      Incidence rates were highest in the first year after the head injury. The overall
      excess incidence rate was very low in mild TBI, only 0.3 per 1000 per year, but
      was higher in severe TBI, with an excess rate of 10 per 1000 per year. Only 7.2%
      of the TBI cases were classified as severe (loss of consciousness or amnesia for
      more than 24 hours, subdural hematoma, or brain contusion). CONCLUSION: The long
      term incidence of seizures beyond the incidence rate of idiopathic epilepsy is
      low after mild or moderate TBI, but is at the rate of 10 excess cases per 1000
      per year in the minority of cases with severe TBI.

PMID- 11317881
TI  - Exercise test on the older patient: is it still as predictive as for the younger
      patient?
AB  - Exercise testing predicts both cardiac events and mortality after age 65, just as
      it does for younger patients. In both age groups, functional aerobic capacity
      itself is a potent indicator of mortality risk. In the elderly, achievement of
      predicted functional aerobic capacity identifies favorable mortality even in the
      presence of CAD and CAD risk factors.

PMID- 11317882
TI  - Diabetes mellitus and life insurance.
AB  - A comprehensive review of the literature of diabetes mellitus, its progression
      and complications is written with respect to the life insurance industry.

PMID- 11317883
TI  - Analysing transformation products of herbicide residues in environmental samples.
AB  - High-performance liquid chromatography (HPLC) methods were developed for the
      optimised determination of five herbicide residues (dichlorprop, isoproturon,
      mecoprop, metsulfuron-methyl and 2,4,5-T) and major metabolites. These compounds
      represent important groups of herbicides and several residues have been found as
      contaminants in groundwater. The methods make it possible to study these
      herbicides and several transformation products through simultaneous detection and
      quantification. Culture media as well as cleaned up extracts from sediment and
      groundwater can be analysed. Using HPLC with UV detection the general limit of
      quantification was 1.8 ng injected corresponding to a detection limit of 1-2
      micrograms/l when analysing a cleaned up extract from a 20 ml water sample. The
      method was verified by analysing herbicide residues in groundwater collected from
      a wetland area. Cleaning up 20 ml groundwater with a residue level of 25
      micrograms/l the general recovery was within 58-82%.

PMID- 11317884
TI  - Methane microprofiles in a sewage biofilm determined with a microscale biosensor.
AB  - Microprofiles of the methane concentration in a 3.5-mm-thick sewage outlet
      biofilm were measured at high spatial and temporal resolution using a microscale
      biosensor for methane. In the freshly collected biofilm, methane was building up
      to a concentration of 175 mumol l-1 at 3 mm depth with a total methanogenesis of
      0.14 mumol m-2 s-1, as compared to an aerobic respiration (including methane
      oxidation) of 0.80 mumol m-2 s-1. A model biofilm was established by
      homogenisation of an in situ biofilm and 12 days of incubation with surplus
      sodium acetate. The homogenised biofilm was able to maintain 50% of the
      methanogenic activity in the absence of external electron donor. Oxygen had only
      a minor effect on the methane production, but aerobic respiration consumed a
      substantial part of the produced methane and was thus an important control on
      methane export from the biofilm. A concentration of 2 mmol l-1 nitrate was shown
      to inhibit methanogenesis only in the upper layer of the biofilm, whereas a
      further addition of 2 mmol l-1 sulphate inhibited methanogenesis in the entire
      biofilm. The study demonstrated the power of the methane microsensor in the study
      of microhabitats with concurrent production and consumption of methane.

PMID- 11317885
TI  - Inactivation of Cryptosporidium parvum oocysts using medium- and low-pressure
      ultraviolet radiation.
AB  - The effect of ultraviolet radiation from low- and medium-pressure mercury arc
      lamps on Cryptosporidium parvum oocysts was studied using a collimated beam
      apparatus. Experiments were conducted using parasites suspended in both filtered
      surface water and phosphate buffered laboratory water. Inactivation of oocysts
      was measured as reduction in infectivity using a CD-1 neonatal mouse model and
      was found to be a non-linear function of UV dose over the range of germicidal
      doses tested (0.8-119 mJ/cm2). Oocyst inactivation increased rapidly with UV dose
      at doses less than 25 mJ/cm2 with two and three log-units inactivation at
      approximately 10 and 25 mJ/cm2, respectively. The cause of significant leveling
      off and tailing in the UV inactivation curve at higher doses was not determined.
      Maximum measured oocyst inactivation ranged from 3.4 to greater than 4.9 log
      units and was dependent on different batches of parasites. Water type and
      temperature, the concentration of oocysts in the suspension, and the UV
      irradiance did not have significant impacts on oocyst inactivation. When compared
      on the basis of germicidal UV dose, the oocysts were equally sensitive to low-
      and medium-pressure UV radiation. With respect to Cryptosporidium, both low- and
      medium-pressure ultraviolet radiation are attractive alternatives to conventional
      chemical disinfection methods in drinking water treatment.

PMID- 11317887
TI  - Effect of nitrogen limitation on performance of toluene degrading biofilters.
AB  - The literature reports conflicting observations regarding the need for nutrient
      addition to biofilters treating contaminated gases. Such conflicts are often
      based on quasi-steady-state performance data collected on biofilters operated
      under continuous loading conditions. In the studies described herein, the impact
      of nitrogen limitations on two toluene-fed biofilters was assessed over a 97-day
      period. The biofilters were packed with polyurethane foam medium and contained
      different initial levels of nitrate-nitrogen. Toluene and CO2 concentration
      profiles were monitored during both normal steady loading conditions and short
      term, unsteady-state transient loading conditions (e.g., shock loads). Packing
      medium samples were periodically removed and analyzed to quantify changes in
      nitrate-nitrogen content over time. Data are presented which show that over long
      time periods (several months), nutrient-induced kinetic limitations diminished
      biofilter performance during transient, unsteady-state conditions even when
      performance during normal steady loading was not adversely affected. Elemental
      analysis of biomass removed from the biofilters support nitrate-nitrogen and CO2
      concentration profile data and clearly illustrate how kinetically limited
      biofilters fail during shock loads even when there is an overall stoichiometric
      excess of nutrients.

PMID- 11317886
TI  - The potential for phosphorus release across the sediment-water interface in an
      eutrophic reservoir dosed with ferric sulphate.
AB  - Alton Water, Suffolk, UK is a pumped storage reservoir that has a history of
      cyanobacterial blooms. Dosing of the input water with ferric sulphate to control
      external phosphorus loading has occurred since 1983. A detailed study of the
      sediment chemistry of the site was carried out between May 1995 and July 1997.
      Sequential phosphorus fraction analysis indicated a decrease along the length of
      the reservoir in sediment labile phosphorus content from 0.62 to 0.08 mg P g-1 dw
      and iron-bound phosphorus content from 3.22 to 0.46 mg P g-1 dw. These gradients
      positively correlated with water column chlorophyll a concentrations reported in
      a parallel study. Labile and iron-bound sediment phosphorus contents were in a
      dynamic equilibrium due to diffusional release, contributing to internal loading
      to the water column. Equilibrium phosphorus concentrations (EPC) determined from
      phosphorus adsorption capacity (PAC) experiments were lower inside the bunded
      region (0.01-0.03 mg P-PO4 l-1) where iron content was greatest compared to
      outside the bund (0.15-0.20 mg P-PO4 l-1) suggesting greater potential for
      diffusional release of phosphorus at the latter site. PAC experiments indicated
      that anaerobic and pH-mediated loadings were of less importance than diffusional
      release, although the latter may have contributed to internal loading in the main
      reservoir. Sulphate concentrations may act to increase the potential for
      anaerobic internal loading near to the pumped input in microstratified sediment.
      Sediment iron content decreased from 250 +/- 13.1 to 51 +/- 4.0 mg Fe g-1 dw
      across the line of a constructed bund at the north-west end near to the pumped
      input, which indicated successful control of dispersal of the fine ferric floc.
      The management implications with regard to phosphorus loadings indicated by these
      results are discussed.

PMID- 11317888
TI  - Assessment of toxicity reduction after metal removal in bioleached sewage sludge.
AB  - Sewage sludge can be applied to land to supply and recycle organic matter and
      nutrients. Trace elements in sludge, however, may accumulate in the soil with
      repeated sludge applications. Reducing metal content may therefore reduce the
      adverse effects of sludge application. The objective of this study was to
      evaluate the efficiency of bioleaching technology in reducing metal content and
      toxicity as measured by a battery of terrestrial and liquid-phase bioassays.
      Sludge-soil mixtures simulating the application of sludge to land were tested by
      means of terrestrial bioassays, barley (Hordeum vulgare L.) seed germination (5
      d) and sprout growth (14 d), lettuce (Lactuca sativa) seed germination (5 d), and
      worm (Eisenia andrei) mortality (14 d). Liquid-phase bioassays, Microtox (Vibrio
      fischeri, 15 min), lettuce root elongation (L. sativa, 5 d), cladoceran mortality
      (Daphnia magna, 48 h), and SOS Chromotest (Escherichia coli) were used after
      elutriation of the sludge. Comparison of the bioassay results (except for D.
      magna) before and after treatment demonstrated that this bioleaching process
      reduced both sludge toxicity and metal content. In addition, lower Cu and Zn
      concentrations found in barley sprouts following treatment supported the
      assumption that the bioleaching process, by decreasing metal content and
      bioavailability, reduced sewage sludge toxicity. This study also emphasized the
      interest of using ecotoxicological bioassays for testing biosolids. In
      particular, the terrestrial bioassays after simulation of land application and
      the Microtox test after sludge elutriation proved to be the most appropriate
      procedures.

PMID- 11317889
TI  - Bioaccumulation of copper(II) and nickel(II) by the non-adapted and adapted
      growing Candida sp.
AB  - The effect of copper(II) and nickel(II) ions on the growth and bioaccumulation
      properties of non-adapted and adapted growing cells of a non-pathogenic Candida
      sp. has been tested under laboratory conditions as a function of initial pH and
      initial metal ion concentration. Optimum pH value for maximum metal ion
      accumulation was determined as 4.0 for both the metal ions. Although the
      copper(II) adapted Candida sp. was capable of removing of copper(II) with the
      maximum specific uptake capacity of 36.9 mg g-1 at 783.6 mg dm-3 initial
      copper(II) concentration, non-adapted Candida was only capable of bioaccumulating
      copper(II) with 23.1 mg g-1 maximum uptake capacity from aqueous solution at
      578.7 mg dm-3 initial copper(II) concentration. The non-adapted and nickel(II)
      adapted Candida cells also showed the highest nickel(II) uptake capacities (46.8
      and 30.8 mg g-1, respectively) at 321.5 and 300.6 mg dm-3 initial nickel(II)
      concentrations, respectively. For both the non-adapted and nickel(II) adapted
      Candida sp., the growth of cells was totally inhibited by 500 mg dm-3 of
      nickel(II) ions. The results also indicated that copper(II) adapted Candida sp.
      has been found to be more efficient to accumulate larger amounts of copper(II)
      than that of nickel(II) bioaccumulated by nickel(II) adapted Candida at higher
      initial metal ion concentrations without loosing its biological activity.

PMID- 11317890
TI  - Partitioning of trace metals before and after biological removal of metals from
      sediments.
AB  - Metal removal by biological solubilization in three strongly contaminated
      sediments was carried out in a two-liter stirred bioreactor. Biological treatment
      yielded metal removal efficiencies in the range of 11-30%, 43-57%, 60-79%, 61
      90%, 18-21%, 0-10% for Pb, Cu, Zn, Cd, Ni and Cr, respectively. The treated
      sediments were then rinsed with a NaCl solution (0.5 M), resulting in an increase
      by nearly 47% in Pb removal for the three sediments, while for other metals (Cu,
      Zn, Cd, Ni, Cr), the NaCl rinse did not seem to allow any significant increase in
      metal solubilization. A standard procedure of sequential selective extraction
      (SSE) was applied to the sediments before and after each treatment. With regard
      to Pb, Zn and Cd, the carbonate bound fractions (2/3 sediments) represented 18
      42% of metals prior to treatment, while the iron and manganese oxides bound
      fraction constituted 39-60% of metals for the three sediments. Between 90 and
      100% of Pb, Zn and Cd removed by the process came from the fractions bound to
      carbonates and from those bound to Fe and Mn oxides. The organic matter and
      sulfide bound fractions contained 65-72% of total Cu present before treatment and
      the process removed, on average, 63% Cu present in this fraction. In contrast, Ni
      and Cr were found mainly in the residual fractions (50-80%). Finally, this
      biological treatment did not solubilize Cr appreciably, while removal of Ni
      mostly originated from the carbonate and Fe/Mn oxides fractions (70-80%).

PMID- 11317891
TI  - Ultrasonic irradiation of carbofuran: decomposition kinetics and reactor
      characterization.
AB  - The sonochemical decomposition of carbofuran (2,3-dihydro-2,2-dimethyl-7
      benzofuranyl,C12H15NO3) in a parallel plate near-field acoustical processor (NAP)
      is reported. Ultrasonic irradiation was performed at 16 and 20 kHz, under a total
      applied power of 1800 W. Carbofuran decomposition was enhanced with increasing
      power densities (1.65 W mL-1-5.55 W mL-1), and with decreasing initial
      concentrations (25 microM vs. 130 microM). The nature of the dissolved gas in
      solution also influenced the observed decomposition rate. The hydrodynamic
      behavior of the NAP reactor was characterized by calculating the Reynolds numbers
      and by performing tracer studies with a conservative tracer, sodium chloride
      (NaCl). The calculated dispersion coefficients indicate an intermediate amount of
      dispersion during operation of the reactor.

PMID- 11317892
TI  - Effects of alcohols, anionic and nonionic surfactants on the reduction of PCE and
      TCE by zero-valent iron.
AB  - The effects of surfactants, sodium dodecyl sulfate (SDS) and Triton X-a00 (TX),
      and alcohols (methanol, ethanol, and propanol) on the dehalogenation of TCE and
      PCE by zero-valent iron were examined. Surface concentrations of PCE and TCE on
      the iron were dependent on aqueous surfactant concentrations. At concentrations
      above the CMC, sorbed halocarbon concentrations declined and concentrations
      associated with solution phase micelles increased. The anionic surfactant SDS
      ([SDS] < CMC) did not affect reduction rates, until the CMC was exceeded after
      which reactivity decreased, possibly due to sequestering of the TCE and PCE in
      mobile micelles. The nonionic TX showed a mixed effect on reactivity, increasing
      the PCE reduction rate, but not affecting TCE removal. Production of TCE from PCE
      increased in the presence of TX. Similar experiments showed that methanol,
      ethanol, and propanol inhibited reduction of TCE and PCE by metallic iron. Zero
      valent iron may be useful in recycling soil washing effluents contaminated with
      TCE and PCE.

PMID- 11317893
TI  - The adsorption of cyanobacterial hepatotoxins from water onto soil during batch
      experiments.
AB  - Public health concerns associated with cyanobacteria, both chronic and acute,
      arise from their ability to produce toxins. Rural communities within Australia
      and those in developing countries require an inexpensive and low-cost method for
      removing toxins from drinking water. A candidate technology is bank filtration.
      Adsorption of cyanobacterial hepatotoxins was measured in batch studies to
      determine the applicability of bank filtration as an efficient removal strategy.
      Five soils with different physicochemical properties were collected from regions
      around South Australia. The soils were mixed with either nodularin or microcystin
      LR in distilled water and buffered solutions (pH 4.8, 6.9 and 9.1). Additionally,
      nodularin was mixed in unbuffered solutions (pH 4.8 and 8.9). The three soils
      with the high clay and/or organic carbon contents (Paringa A, McLaren Flat and
      Lakes Plains) had the higher nodularin adsorption coefficients, ranging from 0.2
      to 16.59 L kg-1. Soil suspensions in acetate buffer (pH 4.8) generally produced
      significantly higher nodularin adsorption coefficients, when compared to the
      other buffer systems. The background interference from the ionic strength of the
      buffers, however, made interpretation of the effect of pH on toxin sorption
      difficult. Increases in solution ionic strength, from freshwater to seawater,
      resulted in corresponding increases in the nodularin adsorption coefficients for
      all sites, except the sandy Hallett Cove site. The implications for bank
      filtration are that higher water pH values and lower salinities will enhance the
      in situ mobility of the toxins, resulting in an increased distance of filtration
      through the river bank before toxin free water could be abstracted for human
      consumption.

PMID- 11317894
TI  - Measurement of biomass activity in drinking water biofilters using a
      respirometric method.
AB  - A simple respirometric method was developed and applied for the measurement of
      biomass activity in bench-scale drinking water biofilters. The results obtained
      with the new method, i.e. biomass respiration potential (BRP), indicated a high
      sensitivity allowing the quantification of the activity of low amounts of
      biomass. The analysis of duplicate samples showed a reasonable reproducibility,
      i.e. average coefficient of variation of 14% (n = 19). The calculation of the
      ratio between biomass activity and the amount of viable biomass (phospholipid) at
      different filter depths indicated a substantial increase of this ratio with
      filter depth. This indicated an increased biomass activity per unit amount of
      viable biomass deeper in the biofilters, where biofilm thickness is low. The
      comparison of the filter profiles of biomass activity and dissolved biodegradable
      organic matter (BOM), expressed as theoretical oxygen demand, showed a high
      correlation between these profiles. Consequently, BRP results appear to be good
      indicators of the BOM removal capacity of the filter biomass. Therefore, BRP
      results can potentially be used in certain cases instead of BOM measurements for
      the assessment of the BOM removal capacity of drinking water biofilters, operated
      under different conditions. This is important because of the relative complexity
      of the measurements of BOM surrogates, e.g. assimilable organic carbon and
      biodegradable dissolved organic carbon, and BOM components.

PMID- 11317895
TI  - Measurement of volatile organic compounds in sediments of the Scheldt estuary and
      the Southern North Sea.
AB  - The concentrations and distribution of 13 priority volatile organic compounds
      (VOCs) were determined in sediments of the Scheldt estuary and the Belgian
      continental shelf, using a modified Tekmar LSC 2000 purge-and-trap system coupled
      to GC-MS. The method allows a sample intake of up to 50 g wet weight and
      detection limits are between 0.003 ng/g (tetrachloromethane) and 0.16 ng/g (m-
      and p-xylene). The repeatability (n = 5) varied between 4% (benzene) and 17%
      (toluene) and the recoveries ranged from 59% (1,1-dichloroethane) to 99%
      (tetrachloromethane). Because of the nature of the contaminants, special
      attention was paid to analyte losses and contamination of the samples during
      storage aboard the research vessel. Spiked sediment samples were prepared in the
      laboratory and stored aboard under the same conditions as the environmental
      samples. The recoveries for these samples varied between 94 and 130%, which
      suggests that storage had no adverse effect on the samples. No detectable VOC
      concentrations were found for most of the sampling stations. However, in the
      Antwerp harbour area, significant concentrations of VOCs were found. The sorption
      behaviour as predicted from laboratory equilibrium partitioning experiments gives
      an indication of the in situ partitioning behaviour of VOCs. Although VOCs in
      sediments should, in general, not be regarded as a major problem in the marine
      environment, high local concentrations may be a cause of concern.

PMID- 11317896
TI  - Long-term changes in watershed nutrient inputs and riverine exports in the Neuse
      River, North Carolina.
AB  - We compared patterns of historical watershed nutrient inputs with in-river
      nutrient loads for the Neuse River, NC. Basin-wide sources of both nitrogen and
      phosphorus have increased substantially during the past century, marked by a
      sharp increase in the last 10 years resulting from an intensification of animal
      production. However, this recent increase is not reflected in changes in river
      loading over the last 20 years. Temporal patterns in river loads more closely
      parallel short-term changes in point sources and cropland nutrient application
      despite their overall lower magnitude. Total phosphorus loads have declined at
      all stations considered, corresponding to a 1988 phosphate detergent ban.
      Nitrogen load temporal patterns vary by location and the nitrogen fraction
      considered. The furthest upstream station exhibited nitrogen decreases after the
      completion of a dam in 1983. At a station just downstream of a rapidly growing
      urban area, the total nitrogen load has increased since the mid-1980s, primarily
      as a nitrate concentration increase. This is consistent with concurrent increases
      in chemical fertilizer use and point source discharges, as well as increased
      nitrification at treatment plants. This increase in nitrate loading is not
      reflected at the most downstream station, where no clear nitrogen trends are
      discernable. The lack of clear downstream nutrient increases suggests that
      current water quality impairment in the lower river and estuary may result from
      chronic nutrient overload rather than recent changes in the watershed. If this is
      true, then the impact of a planned 30% nitrogen loading reduction may not be
      immediately apparent. We calculate that, given annual variability, detecting a
      load reduction of this magnitude will take at least four years, and, should
      nutrients accumulated in the watershed become a significant source, detecting the
      resulting ecological improvements is likely to take substantially longer.

PMID- 11317897
TI  - Ultrafiltration behavior of major ions (Na, Ca, Mg, F, Cl, and SO4) in natural
      waters.
AB  - Aquatic colloids, including macromolecules and microparticles, with sizes ranging
      between 1 nm to 1 micron, play important roles in the mobility and
      bioavailability of heavy metals and other contaminants in natural waters. Cross
      flow ultrafiltration has become one of the most commonly used techniques for
      isolating aquatic colloids. However, the ultrafiltration behavior of chemical
      species remains poorly understood. We report here the permeation behavior of
      major ions (Na, Ca, Mg, F, Cl, and SO4) in natural waters during ultrafiltration
      using an Amicon 1 kDa ultrafiltration membrane (S10N1). Water samples across a
      salinity gradient of 0-20@1000 were collected from the Trinity River and
      Galveston Bay. The permeation behavior of major ions was well predicted by a
      permeation model, resulting in a constant permeation coefficient for each ion.
      The value of the model-derived permeation coefficient (Pc) was 0.99 for Na, 0.97
      for Cl, and 0.95 for F, respectively, in Trinity River waters. Values of Pc close
      to 1 indicate that retention of Na, Cl, and F by the 1 kDa membrane during
      ultrafiltration was indeed minimal (< 1-5%). In contrast, significant (14-36%)
      retention was observed for SO4, Ca, and Mg in Trinity River waters, with a Pc
      value of 0.64, 0.82, and 0.86 for SO4, Ca and Mg, respectively. However, these
      retained major ions can further permeate through the 1 kDa membrane during
      diafiltration with ultrapure water. The selective retention of major ions during
      ultrafiltration may have important implications for the measurement of chemical
      and physical speciation of trace elements when using cross-flow ultrafiltration
      membranes to separate colloidal species from natural waters. Our results also
      demonstrate that the percent retention of major ions during ultrafiltration
      decreases with increasing salinity or ionic strength. This retention is largely
      attributed to electrostatic repulsion by the negatively charged cartridge
      membrane.

PMID- 11317898
TI  - Cost factors and chemical pretreatment effects in the membrane filtration of
      waters containing natural organic matter.
AB  - This paper compares the membrane processes available for water treatment.
      Membranes have the advantage of currently decreasing capital cost, a relatively
      small footprint compared to conventional treatment, generally a reduction in
      chemicals usage and comparably low maintenance requirements. Three membrane
      processes applicable to water treatment, micro- (MF), ultra- (UF), and
      nanofiltration (NF), are compared in terms of intrinsic rejection, variation of
      rejection due to membrane fouling and increase in rejection by ferric chloride
      pretreatment. Twelve different membranes are compared on the basis of their
      membrane pore size which was calculated from their molecular weight cut-off. A
      pore size of < 6 nm is required to achieve substantial (> 50%) organics removal.
      For a fouled membrane this pore size is about 11 nm. UV rejection is higher than
      DOC rejection. Coagulation pretreatment allows a higher rejection of organics by
      MF and UF and the cut-off criterion due to initial membrane pore size is no
      longer valid. A water quality parameter (WQP) is introduced which describes the
      product water quality achieved as a function of colloid, DOC and cation
      rejection. The relationship between log (pore size) and WQP is linear. Estimation
      of membrane costs as a function of WQP suggests that open UF is superior to MF
      (similar cost at higher WQP) and NF is superior to tight UF. Chemical
      pretreatment could compensate for the difference between MF and UF. However, when
      considering chemicals and energy costs, it appears that a process operated at a
      higher energy is cheaper at a guaranteed product quality (less dependent on
      organic type). This argument is further supported by environmental issues of
      chemicals usage, as energy may be provided from renewable sources.

PMID- 11317899
TI  - Contamination of potable roof-collected rainwater in Auckland, New Zealand.
AB  - One-hundred and twenty-five domestic roof-collected rainwater supplies in four
      rural Auckland districts were investigated in a cross-sectional survey to
      determine water quality. Samples of cold faucet water were analysed for physico
      chemical and microbiological determinands, including metals (zinc, copper and
      lead), bacterial indicator organisms--heterotrophic plate count (HPC), total
      coilforms (TC), faecal coliforms (FC), enterococci (ENT), bacterial pathogens
      including Salmonella spp., Legionella spp., Campylobacter spp., Aeromonas spp.
      and the protozoa, Cryptosporidium and Giardia. Twenty-two supplies (17.6%)
      exceeded one or more of the maximum acceptable values (MAV) or maximum guideline
      values for chemical determinands of the New Zealand Drinking Water Standards
      (NZDWS) and 70 (56.0%) supplies exceeded the microbiological criteria of < 1
      FC/100 mL. Eighteen supplies (14.4%) exceeded the NZDWS MAV for lead of 0.01 mg/L
      and three (2.4%) exceeded that for copper, of 2 mg/L. Those supplies with lead or
      galvanised iron comprising part of the roof or collecting system were more likely
      to show lead contamination (p = 0.019) as were those supplies with a pH less than
      7 (p = 0.013). The presence of the indicator organisms HPC, TC, FC and ENT were
      all significantly correlated with one another. Aeromonas spp. were identified in
      20 (16.0%) supplies. There was a positive association between the presence of
      Aeromonas and the bacterial indicator organisms. Households reporting at least
      one member with gastrointestinal symptoms in the month prior to sampling, were
      more likely to have Aeromonas spp. identified in their water supply than those
      households without symptoms (odds ratio 3.22, 95% CI 1.15-9.01, p = 0.021).
      Salmonella typhimurium was detected in one of 115 (0.9%) supplies. Legionella
      spp. and Campylobacter spp. were not detected. There were 50 supplies sampled for
      protozoa (sampling criteria: > or = 30 FC or > or = 60 ENT). Cryptosporidium
      oocysts were detected in 2 (4%) of these. Giardia was not detected. This study
      demonstrates that roof-collected rainwater systems provide potable supplies of
      relatively poor physiochemical and microbiological quality in the Auckland area.
      Further research is required on Aeromonas spp. as potential indicators of both
      microbiological quality and health risk along with design and maintenance
      strategies to minimise contamination of potable roof-collected rainwater
      supplies.

PMID- 11317900
TI  - Solute transport under non-linear sorption and decay.
AB  - Contaminant transport in aquifers is usually represented by a solution to the
      advective-dispersive differential equation. When the contaminant is subject to
      non-linear degradation or decay, or it is characterized by a chemical constituent
      that follows a non-linear sorption isotherm, the resulting differential equation
      is non-linear. Using the method of decomposition, series solutions were obtained
      for the non-linear equation. The series were used to derive and test "simulant"
      solutions that aries using the concept of  double decomposition. Simulant
      solutions are closed-form analytic expressions that approximate part of the
      series These expression are simple, stable, and flexible. They permit an accurate
      forecasting of contaminant propagation     .under non-linearity in laboratory or
      field  investigations at early or prolonged times after the spill. In this
      article, the practical scenario of an instantaneous spill, and that of a constant
      concentration boundary condition, is studied for situations of non-linear decay,
      non-linear Freundlich isotherm, and non-linear Langmuir isotherm.  The solutions
      are verified with limited well-known analytical solutions of the linear reactive
      and non-reactive equations with excellent agreement, and with limited finite
      difference solutions. Plumes undergoing non-linear decay experience a profile re
      scaling with respect to that of linear decay, the degree of which is controlled
      by magnitude of the non-linear parameter b. The direction of the scaling (scaling
      up or scaling down with respect to the linear decay plume) is controlled by the
      magnitude of  C (whether greater or  less than 1) in relation to the magnitude of
      b (whether greater or less than 1). When C>1, values of b<1 produce plumes that
      experience less decay (i.e., are scaled up) than that of the linear decay,
      whereas  values of b> 1 produce non-linear plumes that experience more decay
      (i.e., are scaled down) than that of  the linear decay. The opposite effect is
      observed when concentrations are less than 1. In  other words, when C<1, values
      of   beta<1 produce non-linear plumes that experience more decay (i.e., are
      scaled down) than that of the linear decay, whereas values of   b>1, produce non
      linear plumes that experience less decay (i.e., are scaled up) than that of the
      linear decay. A plume undergoing non-linear sorption according to a Freundlich
      isotherm retards the processses of advection and dispersion with respect to a
      plume with no sorption. Similar to the case of non-linear decay, whether this
      retardation is more or less pronounced than that  of the linear sorption plume
      depends on whether the values of b and C are greater or less than 1. The solution
      presented here for the advective dispersive equation subject to a Freundlich
      sorption isotherm is restricted to concentration greater than 1. When C>1 and
      b<1, the decrease in mobility in the non-linear plume is not as pronounced as
      that of a plume modeled by a linear isotherm. Plume shape may be quite sensitive
      to the values of the non-linear parameters. Plumes with parameter values b<1 (and
      C> 1) exhibit the well-know lack of symmetry with respect to their center of
      mass, sharp fronts, and the tailing effects observed at  hazardous waste sites.
      As the magnitude of the non-linear"retardation" can now be observed
      quantitatively with models presented herein. The models developed also simulate
      the case of b> 1 (i.e., "unfavorable" sorption), which produce a plume even more
      retarded than the linear. The shape of a contaminant plume following a non-linear
      Langmuir isotherm is very sensitive to the magnitude of the  non-linear parameter
      alpha. Approximate solutions for mild  non-linearity are presented.

PMID- 11317901
TI  - Effects of pH and dissolved oxygen on the reduction of hexavalent chromium by
      dissolved ferrous iron in poorly buffered aqueous systems.
AB  - The effects of pH and dissolved oxygen (DO) on the reduction of Cr(VI) by
      dissolved Fe(II) were investigated for aqueous solutions having relatively low
      buffering capacities. All solutions were maintained at a constant ionic strength
      (generally 0.05 M) and temperature (23 +/- 2 degrees C). For the majority of the
      experiments conducted, initial concentrations of Fe(II) and Cr(VI) were 50 and 20
      microM, respectively, representing a deficient amount of Fe(II) (i.e.
      nonstoichiometric conditions). Experiments conducted in the absence and presence
      of DO were performed in an anaerobic chamber and in vessels open to the
      atmosphere, respectively. Specific initial pH values were obtained by adjusting
      the pH of Cr(VI) and Fe(II) stock solutions prior to their mixing or by spiking
      Cr(VI)-Fe(II) systems with strong base to rapidly increase the pH in situ.
      Consistent with previous reports, Cr(VI) reduction rates for our systems
      increased with increasing pH (pH ranges of 3.5-6 and 3.5-7.2 for oxic and anoxic
      experiments, respectively). Because of our poorly buffered experimental systems,
      pH values decreased over the course of the reactions which, in turn, caused
      decreases in the reduction rates with time. Spiking some experimental systems
      with NaOH to rapidly raise the pH resulted in faster rates of Cr(VI) reduction
      than when the pH was adjusted prior to mixing the stock solutions together; this
      observation is likely due to the presence of microenvironments in the reactors
      for which local, short-term pH values greatly exceed the equilibrium value (i.e.
      mixing is slower than the reduction reaction in these high pH microenvironments).
      The molar ratios of Fe(II) oxidized to Cr(VI) reduced were close to the expected
      stoichiometric value of 3 for the majority of our experimental systems, which
      shows that DO will not cause a serious interference in most applications using
      Fe(II) to reduce Cr(VI).

PMID- 11317902
TI  - Fate of indicator microorganisms, Giardia and Cryptosporidium in subsurface flow
      constructed wetlands.
AB  - Limited information is available on the ability of subsurface flow wetlands to
      remove enteric pathogens. Two multi-species wetlands, one receiving secondary
      sewage effluent and the other potable (disinfected) groundwater were studied from
      February 1995 to August 1996, at the Pima County Constructed Ecosystems Research
      Facility in Tucson, Arizona. Each wetland had a retention time of approximately 4
      days. The objectives of this study were (1) to evaluate the ability of multi
      species subsurface wetlands to physically remove Giardia cysts; Cryptosporidium
      oocysts, total and fecal coliforms, and coliphages; and (2) to determine the
      likely impact of local wildlife on the occurrence of these indicators and
      pathogens. In the wetland receiving secondary sewage effluent, total coliforms
      were reduced by an average of 98.8% and fecal coliforms by 98.2%. Coliphage were
      reduced by an average of 95.2%. Both Giardia cysts and Cryptosporidium oocysts
      were reduced by an average of 87.8 and 64.2%, respectively. In the wetland
      receiving disinfected groundwater, an average of 1.3 x 10(2) total coliforms/100
      mL and 22.3 fecal coliforms/100 mL were most likely contributed by both flora and
      fauna. No parasites or coliphages were detected.

PMID- 11317903
TI  - Factors affecting the performance of stormwater treatment wetlands.
AB  - Data from 35 studies on 49 wetland systems used to treat stormwater runoff or
      runoff-impacted surface waters were examined and compared in order to identify
      any obvious trends that may aid future stormwater treatment wetland design
      efforts. Despite the intermittent nature of hydrologic and pollutant inputs from
      stormwater runoff, our analysis demonstrates that steady-state first-order plug
      flow models commonly used to analyze wastewater treatment wetlands can be adapted
      for use with stormwater wetlands. Long-term pollutant removals are analyzed as
      functions of long-term mean hydraulic loading rate and nominal detention time.
      First-order removal rate constants for total phosphorus, ammonia, and nitrate
      generated in this fashion are demonstrated to be similar to values reported in
      the literature for wastewater treatment wetlands. Constituent removals are also
      demonstrated via regression analyses to be functions of the ratio of wetland area
      to watershed area. Resulting equations between these variables can be used as
      preliminary design tools in the absence of more site-specific details, with the
      understanding that they should be employed cautiously.

PMID- 11317904
TI  - Comparison of conventional and two-stage reversible flow, static-bed
      biodenitrification reactors.
AB  - This paper compares the operation of a traditional single-stage system with a two
      stage, reversible flow biodenitrification system for removing nitrates from
      drinking water. The purpose of this study was to investigate the ability of these
      two-stage systems to remove nitrate and residual organics from treated water as
      compared to single-stage units. In the reversible flow system, the second-stage
      (i.e. follow) reactor is operated in series with the first-stage (i.e. lead)
      reactor. After a given period of operation, the flow regime is reversed so that
      the follow reactor becomes the lead one and vice versa. The active solids
      remaining in the follow reactor (previously the lead one) are capable of removing
      residual soluble organics and nitrates to levels below the concentrations
      provided by single-stage units particularly at HRTs as low as 0.5 h. Nitrate
      nitrogen removal efficiency improved slightly from 98 to 99.5% for the single-
      and two-stage systems, respectively. Most notably, reversible flow reactors were
      found to reduce long-term effluent residual organics concentrations with an
      average of approximately 1/3 that of the single-stage system. Also the reversible
      flow system, with its design redundancy, demonstrated the ability to receive
      extreme shock loads with no sustained loss of treatment efficiency.

PMID- 11317905
TI  - Spatial and temporal evolution of trihalomethanes in three water distribution
      systems.
AB  - Spatial and seasonal changes in trihalomethane (THM) concentrations were
      investigated in three distribution systems of Quebec (Canada) which are supplied
      by different surface waters and which use a variety of physicochemical treatment
      strategies. The investigation was based on an intensive 25-week sampling
      programme, undertaken at a time of year when the temperature of southern Quebec
      surface waters exceeds 4 degrees C (April-November). THMs and other water quality
      and operational parameters were monitored at points along the distribution system
      -between the treatment plant and the system extremities--which represented
      variable residence times of water. Results showed that THM concentrations vary
      significantly (from 1.5 to 2 times, depending on the utility) between finished
      waters as they leave the plant and water at the system extremities. When water
      temperature exceeds 15 degrees C, spatial THM variations are particularly high
      (from 2 to 4 times, depending on the utility). The development of multivariate
      regression models showed that water temperature was a better predictor of THM
      seasonal variability than chlorine dose, surrogates of natural organic matter and
      pH. Also, initial THM formation (in finished waters leaving the plant) was a good
      predictor of THM levels at distribution system extremities.

PMID- 11317906
TI  - Kinetics of phthalate reactions with ammonium hydroxide in aqueous matrix.
AB  - Common phthalate pollutants, such as dimethyl phthalate and diethyl phthalate
      found in aqueous environmental matrices react with ammonium hydroxide at ordinary
      temperatures exhibiting an overall reaction order in the range 1.3-1.4. While the
      reaction is of first order with respect to the phthalate, the order of reaction
      is fractional in ammonium hydroxide. The rate constants for the reactions of
      these two phthalates in alkaline waters at ambient temperatures are in the range
      1.3 x 10(-4) and 8.5 x 10(-5) Lx/mol s. Under these conditions the estimated half
      lives for dimethyl phthalate and diethyl phthalate at a concentration of each at
      20 mg/L is 4.5 and 14 h, respectively. Other phthalates are expected to exhibit
      similar kinetics in their base hydrolysis with NH4OH. Thus, the presence of both
      the phthalate esters and ammonia or ammonium salts in the water under alkaline
      conditions may result in their self-removal by hydrolysis.

PMID- 11317907
TI  - Evaluation of the fern Azolla for growth, nitrogen and phosphorus removal from
      wastewater.
AB  - Water fern (Azolla filiculoides Lam.) has been assessed for nitrogen and
      phosphorus removal in outdoor experiments comparing sewage water (S) from an
      experimental aquaculture plant, well water (W) and mineral growth medium Hoagland
      (H). The experiments were undertaken during the spring and the summer. The yield
      of fern biomass and nitrogenase activity was higher in H than in W and S waters.
      The enzyme activity had a decreasing trend with significant differences (p <
      0.05) in the three waters. Peroxidase (POD) activity in April decreased with
      significative differences in W and S waters (p < 0.05). The electrical
      conductivity and the concentrations of NO3- in the three waters decreased
      significantly (p < 0.05). The highest removal of nitrate from the media was
      obtained in July. In S water, NO2- concentration decreased, while it increased in
      W water. PO(4)3- concentration was very low in W and S waters and decreased in H
      medium. The results obtained confirm the ability of the fern to grow in sewage
      water.

PMID- 11317908
TI  - Analyzing haloacetic acids using gas chromatography/mass spectrometry.
AB  - Haloacetic acids (HAAs) are a group of disinfection by-products formed in
      chlorinated water. Due to their potential health effects and widespread
      occurrences, HAAs are regulated in drinking water in the United States under a
      promulgated regulation. To better control the formation of HAAs in drinking
      water, a reliable and accurate analytical method is needed for HAA monitoring. In
      the present study, a liquid-liquid microextraction, acidic methanol
      derivatization, and gas chromatography/mass spectrometry (GC/MS) detection method
      was developed for determining HAAs and dalapon in drinking water. The newly
      developed method is capable of analyzing all nine HAAs and dalapon at microgram/l
      levels. The method performance, including the method detection limit (MDL) and
      spiking recovery, was evaluated. In comparison to EPA Method 552.2, which uses
      gas chromatography/electron capture detection (GC/ECD), this GC/MS method gave
      cleaner baselines and had few interfering peaks. For each of all nine HAAs and
      dalapon, the MDL was less than 1 microgram/l and the spiking recovery ranged from
      73 to 165%. Using the GC/MS method, the run time could also be significantly
      reduced without compromising the analytical results. Further study is needed to
      fine-tune this GC/MS based analytical method, especially in the detection of
      brominated trihaloacetic acids and monochloroacetic acid.

PMID- 11317909
TI  - Removal and recovery of p-phenylenediamines developing compounds from
      photofinishing lab-washwater using clinoptilolite tuffs from Greece.
AB  - Clinoptilolite tuffs from areas in Thrace region of Greece are compared with
      synthetic zeolites NaY and NH4Y for the uptake of N4-ethyl-N4-(2
      methansulphonamidoethyl)-2-methyl-1,4-phenylenediamin (sesquisulphate,
      monohydrate) with the trade name CD-3 for the purpose to be used for clean-up and
      recycling photo-finishing and photo-developing washwaters. The cation-exchange
      capacity is found to be 6.15-11.1 mg/g for zeoliferous tuffs at equilibrium
      concentration of 50 ppm CD-3 in aqueous solution compared to 65.0 mg/g of NaY and
      48.2 mg/g for NH4Y synthetic zeolites corresponding to the removal of CD-3 from
      120 to 2001 of 50 ppm aqueous solution per kg of natural zeoliferous tuff; this
      capacity is only 6-10 times lower than type-Y synthetic zeolite. Initial rates of
      uptake are 20.8 mg/l/min for natural and 38.5 mg/l/min for synthetic zeolites.
      Regeneration levels of 55, 23, 35, and 33% are obtained for MCH, SF, NaY, and
      NH4Y, respectively. The rapid and almost complete uptake of CD-3 from its aqueous
      solutions at low CD-3 concentrations by the natural zeolites is promising for
      such an application.

PMID- 11317910
TI  - Using chemical and physical parameters to define the quality of Pardo River water
      (Botucatu-SP-Brazil).
AB  - This paper aims to study the ecological system of the Pardo River, at the source
      and lower-order passages, which are in the Botucatu area, Sao Paulo State,
      Brazil. This study was carried out to determine water quality with some chemical
      physical indicators, coliforms, and chemical species of samples taken monthly,
      1995/02-1996/01, from eight sampling stations sited along the Pardo River. The
      results in the river monitoring are discussed based on annual averages, analysis
      of variance, and compared to Tukey's Studentized Range--HSD, and principal
      component analysis (PCA) was applied to normalize data to assess association
      between variables. We can conclude that the variables used are very efficient for
      identifying and that the dry season shows the worst water quality. These were
      caused by organic matter, nutrients (originate) from anthropogenic sources
      (spatial sources) and mainly municipal wastewater, affecting the quality and
      hydrochemistry of the river water, which have been differentiated and assigned to
      polluting sources. Meanwhile, the degree of degradation of the Pardo River is low
      (sewage treatment carried out by the city of Pardinho is efficient), leaving the
      water of the river suitable for use by the population of Botucatu, after
      conventional treatment (Conama, Resolucao No. 20, CONAMA, Brazilia DF, 09-23,
      1986--the water of the Pardo river is classified as level 03).

PMID- 11317911
TI  - Nd isotopes and water mixing phenomena in groundwaters from Palmottu (Finland).
AB  - The Palmottu uranium ore deposit, located within a granitic host rock in southern
      Finland, is an excellent setting for conducting analogue studies to assess
      radionuclide transport from the uranium deposit fractured crystalline host rock.
      In this context, Nd isotope ratios are used to establish the degree of water-rock
      interaction (WRI) and to clarify mixing processes within the groundwaters.
      Variations in Nd isotopes in selected water types from the Palmottu hydrosystem
      provide new information on the mixing history.

PMID- 11317912
TI  - Helicobacter sp. recovered from drinking water biofilm sampled from a water
      distribution system.
AB  - Workers examining the transmission route(s) and reservoir(s) of infection for
      Helicobacter pylori have postulated several environmental reservoirs for the
      organism, including water. Such work has, to date, concentrated on the bulk
      liquid in drinking water systems rather than on biofilms. Previous investigations
      by the authors have suggested biofilms in water distribution systems are a
      possible reservoir of infection. This current study comprised of an analysis of a
      section of cast iron mains distribution pipe removed from an urban environment in
      the north-east of Scotland during routine maintenance work. Immediately upon
      removal of the pipe section, the interior lumen was swabbed to remove the biofilm
      layer. Subsequent analysis for the presence of Helicobacter DNA using a nested
      PCR approach produced a positive result. This data provides the first evidence
      for the existence of Helicobacter in biofilms found in water distribution systems
      anywhere in the world.

PMID- 11317913
TI  - [Prevalence and management of pain in a hospital: a cross-sectional study].
AB  - OBJECTIVES: Improved management of pain, particularly in inpatients, is a public
      health priority. We conducted this study to ascertain current practices and
      identify indications useful for measuring their impact. PATIENTS AND METHODS: A
      "given day" cross-sectional study was conducted in 18 units (11 medicine units
      and 7 surgery and obstetrics units) at the Cochin Hospital, Paris. All patients
      hospitalized over 24 hours were included in the study. A short one-page
      questionnaire was administered by an investigator (nurse or physician) after the
      patient agreed to participate in the study. All pertinent information concerning
      pain at admission and/or during the 24 hours of hospitalization (quantified on a
      simple verbal scale), percent pain relief compared with the initial level, and
      any circumstances leading to an increase in the pain level during hospitalization
      were recorded. Data were also collected on antalgesia prescription administered
      the day of the survey. Social and demographic data as well as discharge
      diagnosis(es) were also recorded. RESULTS: Nearly 60% of the patients stated they
      had experienced pain at the time of admission or during the 24-h preceding the
      survey. In medicine units, 29% of the inpatients with pain were not given any
      anti-pain treatment (this percentage was 12% in surgery) and 35% stated their
      pain had been relieved by less than 50% (13% of the patients in surgery).
      Hospitalization in a medicine unit was associated with fewer and less effective
      prescriptions in patients experiencing pain. CONCLUSION: Regular and simple
      indications, specifically the number of patients complaining of pain who have not
      been given an antalgesic, would provide the health care team with a measurement
      of pain management useful for assessing its impact and improving patient care.

PMID- 11317914
TI  - [Tension-free procedures: progress in the treatment of inguinal hernia].
AB  - OBJECTIVE: Tension-free procedures are aimed to minimize post-operative pain and
      rate of recurrence, by replacing sutures under tension by a mesh without any
      approximation of the margins of the hernial orifice. Moreover they offer the
      advantage of being performed under local or epidural anesthesia. The aim of this
      study was to verify, by a prospective multicentre evaluation, if the results
      attributed to these procedures are obtained in current practice. RESULTS:
      Evaluation involved 435 hernias, treated by Lichtenstein procedure, Gilbert plug
      and Perfix plug. There were 19 postoperative benign complications (4.4%). The
      durations of analgesics consumption, post-operative hospital stay, cessation of
      normal activities and time off work [mean, [(SD), (extremes)]] were 3.3 days
      [(3.9) (0-60)], 1.3 days [(1.1) (0-16)], 4.5 days [(3.1) (0-34)] and 15.4 days
      [(10.2) (0.60)] respectively. With a mean follow-up of 36 months [(14) (6-67)],
      423 hernias (97.2%) were assessed. Two (0.5%) recurrences occurred. Twenty three
      patients had secondary troubles (5.8%): 21 patients complained of chronic pain,
      one had atrophy of the testis and one plug had to be removed. CONCLUSION: Our
      results confirm that tension-free procedures are minimally invasive, induce few
      benign postoperative complications, low pain and allow early return to normal
      activity.

PMID- 11317915
TI  - [Thrombotic microangiopathy during HIV infection. A retrospective study performed
      in infectious diseases units in southern France].
AB  - OBJECTIVES: To describe and analyze the clinical and biological manifestations of
      thrombotic microangiopathy (TMA) and evaluate the therapeutic strategies.
      METHODS: A retrospective study was performed in 14 infectious diseases units of
      southern France. All HIV patients presenting TMA during the last decade were
      selected (n = 14). RESULTS: The principle signs observed, aside from defining TMA
      (association of microangiopathic hemolytic anemia, thrombocytopenia and renal
      failure), were diarrhea (n = 9) and a high level of lacticodehydrogenase (LDH).
      Patients were at an advanced stage of HIV infection (median of CD4+ cells counts
      = 70/mm3). Specific etiology was identified in 7 cases: bacterial infection (n =
      5), CMV retinitis associated with Kaposi's sarcoma (n = 1) and intravenous drug
      use (n = 1). Various treatments were used: plasmatic exchange (5 cases), fresh
      frozen plasma (6 cases), steroid therapy (4 cases), acetyl salicylic acid (3
      cases), adaptation of antiretroviral treatment (3 cases). The global prognostic
      was poor with 50% mortality within 2 months. A high level of LDH (> 2500 UI/L)
      was associated with premature death in 5 of the 6 cases observed. CONCLUSION: Our
      data confirm the severity of TMA in case of HIV infection. The common treatment
      remains the use of plasmatic exchange and fresh frozen plasma; an optimal
      antiretroviral therapy must be associated.

PMID- 11317916
TI  - [Corticoid impregnation due to the use of depigmenting cosmetics].

PMID- 11317917
TI  - [Mediterranean spotted fever complicated by myocarditis].

PMID- 11317918
TI  - [The notion of health].
AB  - There has been a good deal of discussion and though on the notion of health. The
      most widely employed definitions can be termed "physiological", focusing on
      organs and normality. These definitions result from the development of medicine
      around the concept of disease, leading Boissier de Sauvages, author of a disease
      classification that continued to be used until the current classification
      proposed by the WHO, to state that "health, considered in its historical context,
      is the concourse of phenomena designating life and perfect structures". The
      current WHO classification goes beyond the notion of disease and introduces the
      very positive concept of theoretically total "well-being". In light of the
      evolution in the reasons why people call upon the health care system, we propose
      considering health as an equilibrium describing an individual's capacity to cope
      with the environment and taking into account the available health care resources.
      Thus, as proposed by Rene Dubos, health is a "relatively trouble-free state
      devoid of suffering". We integrate the notions of handicap that we have developed
      in a four-dimensional approach where subjectivity plays a very important role.
      Our proposal totally changes the notion of cure: one can be diabetic and cured,
      paraplegic and cured.

PMID- 11317919
TI  - [Management systems of the quality of health care in Quebec hospitals].
AB  - OBJECTIVES: The aim of this study was to take stock of the development of quality
      management systems in the Quebec health care services. METHODS: The study relied
      on semi-guided interviews and on a documentary analysis. It concerned the
      structure and the activity of quality management in 4 Montreal university
      hospitals as well as on outside organizations dealing with quality of care.
      RESULTS: Quality management of the health care services is dealt with by council
      on health care accreditation and regional health and social services agencies. In
      hospitals, the quality of services is managed by structures created by the
      administration council and the top management: the piloting committee, the head
      of quality assurance, the executive committees and the multidisciplinary team or
      self-evaluation of the hospital, and development of plans for improvement. Other
      activities are management of complaints, users satisfaction evaluation and follow
      up of indicators. CONCLUSIONS: This system of quality management of services is
      currently expanding. This change of paradigm leads to accepting the view of
      services users and to change quality management methods. Those methods have
      evolved from normative approach to a continuous quality improvement approach.

PMID- 11317920
TI  - [Remarks on the semantics of "iatrogenic"].

PMID- 11317921
TI  - [Pharmacokinetic changes in renal failure].
AB  - DRUG PHARMACOKINETICS: One of the first steps in the clinical development of
      drugs consists in studies of their pharmacokinetics. Dosage and administration
      interval necessary to ensure secure and efficient plasma levels are derived from
      the values of pharmacokinetic parameters. Renal disease usually implies multiple
      pathophysiological modifications that generate alteration in drugs
      pharmacokinetic profile. Those modifications mainly occur on elimination phase
      but also to a significant extent on absorption and distribution.
      PATHOPHYSIOLOGICAL CHANGES: In this article we describe potential alteration in
      drugs absorption, distribution (volume of distribution, binding to plasma
      proteins), hepatic or renal metabolism, and parent compound and/or metabolites
      elimination in patients with renal insufficiency. Furthermore, in patients with
      end-stage renal disease treated by dialysis, drugs are likely to be removed by
      extracorporal epuration and dosage and/or interval modifications should thus be
      applied to treatments in those patients. CLINICAL ASSESSMENT: Pharmacokinetics of
      drugs should be evaluated in patients with renal failure to determine whereas
      dosage and/or administration interval should thus be modified to enhance
      tolerance and pharmacological efficacy. Such studies are obviously necessary for
      drugs that are mainly excreted unchanged in urine. They should also be performed
      for drugs that are mainly degraded in the liver with emphasis on metabolites
      pharmacokinetics.

PMID- 11317922
TI  - [Allergies to ketoprofen gels].
AB  - A COMMON OBSERVATION: Ketoprofene gels, widely used to treat benign conditions,
      can provoke local intolerance. The most commonly reported clinical features
      include eczema, sometimes severe acute contact photoallergy that often spread
      beyond the site of application and may even lead to a long-duration generalized
      reaction. DIAGNOSIS: Photoallergological tests allow positive diagnosis of the
      ketoprofene-induced contact photosensitization and underline the role of the
      benzophenone ring, explaining certain cross allergies with fenofibrate and
      oxybenzone. PRECAUTIONS FOR USE: The primary rule is to avoid sun exposure,
      requiring better information for prescribers and patients.

PMID- 11317923
TI  - [Treatment of inflammatory diseases: safety of long-term use of infliximab].
AB  - INFLIXIMAB: Is a chimeric antitumour necrosis factor-alpha monoclonal antibody
      that has been studied for the treatment of Crohn's disease and rheumatoid
      arthritis. A LONG TERM SAFETY: In several placebo controlled, randomized clinical
      trials and open trials, 771 patients have been given infliximab (a further 192
      received placebo). Follow-up for safety has included the time of study (12 weeks
      after the last infusion), plus 3 additional years. GENERAL TOLERANCE: Acute
      infusion reactions (headache, fever, chills, urticaria, chest pain) were seen in
      17% of patients receiving infliximab compared with 7% of those receiving placebo.
      While infections were reported more frequently overall in the patients given
      infliximab (26% over 27 weeks of follow-up versus 16% of placebo-treated patients
      over 20 weeks of follow-up), there was no increased risk of serious infections.
      There was no difference in the overall mortality rate between the groups. AT THE
      POINT OF VIEW IMMUNOLOGIC: While low titres of autoantibodies developed in less
      than 10% of patients, drug-induced lupus was seen in less than 1%, with these
      cases resolving upon discontinuation of the drug. Overall, infliximab showed an
      acceptable safety profile.

PMID- 11317924
TI  - [Glucose-6-phosphate dehydrogenase et neonatal jaundice].
AB  - OBJECTIVE: Since 1986, quantification of G6PD activity has been a routine test
      for all babies born at the public maternity hospitals of Marseilles. The
      objective of our study was to determine the prevalence of G6PD deficiency in the
      population tested and to evaluate the relative risk of neonatal jaundice in
      newborns with G6PD deficiency. METHODS: Neonatal screening is performed on cord
      blood by spectrophotometric measurements of G6PD activity. A group of 7779
      newborns was studied retrospectively. The occurrence of neonatal jaundice was
      evaluated in 85 children with G6PD deficiency and compared to 85 children with
      normal G6PD activity. RESULTS: The incidence of G6PD deficiency in male newborns
      was found to be 2.1%. The relative risk for neonatal jaundice in the G6PD
      deficient population compared to the non-deficient population is estimated to be
      2.6. CONCLUSION: Neonatal jaundice with pathological hyperbilirubinemia develops
      more frequently in cases of G6PD deficiency. The early characterization of G6PD
      activity provides an etiological diagnosis for neonatal jaundice, as well as the
      opportunity to give the newborn's family information concerning hemolytic crisis
      prevention.

PMID- 11317925
TI  - [Means syndrome. 8 cases].
AB  - BACKGROUND: Euthyroid Graves' disease is defined as an ophthalmopathy without
      dysthyroidism. We report 8 cases in 6 women and 2 men with an average follow-up
      of 16 months after diagnosis. CASE REPORTS: Unilateral ex-opythalmos was the
      first and most frequent sign. Ultrasonographic and immunological thyroid
      abnormalities were frequent but of questionable significance. Thyroid hormone
      levels continued to remain normal. The orbital CT-scan, used to screen for infra
      clinical exophthalmos, evidenced focal or diffuse hypertrophy of the extraocular
      muscles and normal tendon insertions. More than 3 years after diagnosis, only one
      patient developed overt Graves' disease and clinical signs resolved spontaneously
      in one other. DISCUSSION: In mild to moderate forms of euthyroid Grave's disease,
      therapeutic abstention is advisable. Corticosteroids and orbital radiotherapy are
      interesting options in functionally disabling forms. Decompressive surgery is
      rarely needed.

PMID- 11317926
TI  - [Stevens-Johnson syndrome followed by Gougerot-Sjogren syndrome].
AB  - BACKGROUND: Sicca syndrome after Stevens-Johnson syndrome is classically
      described. However, to our knowledge, authentic Sjogren's syndrome following
      epidermal necrolysis has not been described previously. CASE REPORT: A 36-year
      old woman with Steven-Johnson syndrome developed transient hepatitis and a
      persistent sicca syndrome. Fourteen years later an authentic Sjogren's syndrome
      was identified with presence of antinuclear and anti-SSA antibodies and
      lymphocytes infiltration of the accessory salivary glands, i.e. grade IV disease
      in the Chisholm classification. DISCUSSION: The initial mucosal destruction
      observed in our patients may have laid the ground for Sjogren's syndrome via
      abnormal antigen presentation in a predisposed dysimmune context.

PMID- 11317927
TI  - [Buruli ulcer in Togo: 21 cases].

PMID- 11317928
TI  - [Postoperative rhabdomyolysis secondary to diaphragmatic necrosis].

PMID- 11317929
TI  - [Absence of serological evidence of West Nile virus involvement in
      meningoencephalitis in southeastern France].

PMID- 11317930
TI  - [Risk of venous thromboembolism among users of third-generation oral
      contraceptives].

PMID- 11317931
TI  - [Practice guideline for the diagnosis of Alzheimer's disease].

PMID- 11317932
TI  - [Comments on the practice guideline for the diagnosis of Alzheimer's disease].

PMID- 11317933
TI  - [When can one be sure to be certain?].

PMID- 11317935
TI  - [Cancer of the prostate: influence of nutritional factors. General nutritional
      factors].
AB  - OBESITY: Studies attempting to establish an epidemiological link between body
      mass index and the risk of cancer of the prostate have been contradictory. ENERGY
      INTAKE: No straightforward relationship between energy intake and cancer of the
      prostate has been identified. FAR INTAKE: According to epidemiology studies,
      there is a correlation between high-fat diet and the incidence of cancer of the
      prostate. It has thus been demonstrated that men whose diet contains more than 30
      to 40% fat have a higher risk of developing cancer of the prostate than those
      whose diet contains less than 30% fat. In addition, high-fat diets favor
      progression of tumors in elderly subjects. ROLE OF SATURATED FAT: Saturated fat
      has been implicated most often in the development of cancer of the prostate, high
      intake being correlated with shorter survival after diagnosis of cancer.

PMID- 11317934
TI  - [Melanoma: role of ultraviolet radiation: from physiology to pathology].
AB  - EPIDEMIOLOGIC DATA: The frequency of malignant melanoma, by far the most fatal
      skin cancer, has increased by a factor of approximately 15 in the past 60 years.
      The factors underlying this rapid increase are incompletely understood, although
      ultraviolet radiations are likely strongly implicated. Epidemiologic studies
      demonstrate the role of altered patterns of sun exposure, and overexposition to
      UVA radiation, as confirmed by experimental data on animal models. BIOLOGICAL
      ASPECTS: Melanin produced by melanocytes has a photoprotective function in the
      skin, whereas UVB-induced DNA damage enhance the repair capacity of these cells.
      However, this photoprotective effect is not induced by intense intermittent sun
      exposure. In addition, melanocytes demonstrate resistance to UVB-induced
      apoptosis and are thus at high risk for incorporating UV-induced mutations.
      MOLECULAR ASPECTS: Different mutations in susceptibility genes (CDKN2A, INK4), or
      in genes implicated in control of cell cycle or maintenance of cell integrity
      (DNA repair) are involved in initiation and promotion steps of
      melanocarcinogenesis. Moreover, tumor progression is stimulated by UVB through
      the activation of different target genes that are implicated in control of
      melanoma environment (immune surveillance, angiogenesis, growth factors...).

PMID- 11317936
TI  - [Cancer of the prostate: influence of nutritional factors. Vitamins, antioxidants
      and trace elements].
AB  - CANCER OF THE PROSTATE AND VITAMINS: Four vitamins have been studied, vitamins A,
      E, D and C. the results of these studies have been contradictory. Vitamin A and
      vitamin E would have a protective effect. ANTIOXIDANTS: Carotenes have an
      activity similar to that of vitamin A. Beta-carotene was positively associated
      with risk of cancer of the prostate in one study while two others were unable to
      demonstrate any relationship. Lycopene, the red color in fruits and vegetables,
      particularly tomatoes, would contribute to a lower risk of prostate cancer. TRACE
      ELEMENTS: Cadmium would increase the risk of cancer while selenium would have a
      protective effect. However studies concerning selenium carry certain
      methodological biases.

PMID- 11317937
TI  - [Cancer of the prostate: influence of nutritional factors. A new nutritional
      approach].
AB  - FIBERS: A group of vegetarian subjects have been shown to have a lower risk of
      cancer of the prostate than a control group. But the exact role of food fiber
      remains to be determined because plant foods also have an antioxidant effect on
      their own. PLANT PRODUCTS AND EXTRACTS: A compound called PD SPEC has been showed
      to have antitumor effects both in vitro and in vivo. Evaluated in patients with a
      cancer escaping hormone control, the clinical response was a lower level of
      prostate specific antigen (PSA). SOYBEANS: Several studies have demonstrated the
      interesting properties of soybeans. No study has however been able to demonstrate
      the optimal dose per day. A prospective study is currently under way using a 40
      g/day dose. OVERALL NUTRITIONAL APPROACH: Several studies are being conducted
      using a proposed diet where 15% of the total energy intake comes from fat
      (associated with a low saturated/unsaturated ratio), high fiber content (18 g/100
      kcal) and 40 g daily soybean protein. Although large-scale studies with rigorous
      methodology are lacking, an overall nutritional approach could be an interesting
      strategy for the management of cancer of the prostate.

PMID- 11317938
TI  - [Symptomatic subcutaneous iliac empyema in lumbar Pott's disease].

PMID- 11317939
TI  - Detection of epitopes in glycosaminoglycans immobilized on hydrophobic membranes.
AB  - Glycosaminoglycans (GAGs) are linear carbohydrate polymers expressed on all cell
      surfaces, and bind growth factors that recognize specific disaccharide sequences.
      Such sequences in the GAG chain are not genetically determined but may be
      assembled by the cell in response to environmental changes. GAGs are strongly
      hydrophilic and negatively charged molecules that do not bind well to either
      polystyrene surfaces or to hydrophobic blotting membranes. Cationic detergents
      were used to derivatize hydrophobic membranes to become hydrophilic and
      positively charged. Binding of GAGs to derivatized membranes was optimized
      regarding pH and ionic strength. Five different monoclonal antibodies (Mab) were
      used to detect sequence epitopes in immobilized GAGs. Parallel samples were
      stained with Alcian Blue and the staining intensities were quantitated by
      scanning and densitometry. By calculating the ratio between the antibody staining
      (epitope) and Alcian Blue staining (mass), the epitope density, i.e. the number
      of repetitive epitopes per mass, is obtained. The epitope density with each
      antibody was different with different GAGs. Some epitopes were common in GAG,
      i.e. highly repetitive epitopes. Some epitopes were rare and possibly expressed
      only once per GAG molecule, i.e. low degree of repetition. An epitope density
      profile was obtained when each sample was stained with all antibodies and their
      epitope densities calculated at the plateau level. The epitope profile is an
      indirect measure of the sequence variability in GAGs. Determination of epitope
      density and profile can be used to characterize a GAG population and to
      discriminate between different populations with similar chemical composition.

PMID- 11317940
TI  - Context-dependent and invariant associations between APOE genotype and levels of
      lipoproteins and risk of ischemic heart disease: a review.
AB  - Apolipoprotein E (APOE) plays a pivotal role in the catabolism of triglyceride
      rich lipoproteins by serving as a ligand for lipoprotein receptors. The common
      three-allele (epsilon 2/epsilon 3/epsilon 4) variation in the APOE gene is the
      most studied susceptibility polymorphism to date, identified in more than 50
      different populations worldwide. Differences in the associations between APOE
      genotype and lipids, lipoproteins, and risk of ischemic heart disease between and
      within studies have raised the possibility that this gene is expressed in a
      context-dependent rather than invariant manner. The objective of this review was
      to focus on studies that in particular yield information about such context
      dependent associations of the APOE polymorphism. The well-documented pattern of
      increasing cholesterol levels from epsilon 2 to epsilon 3 to epsilon 4 seems
      invariant across different populations; however, the magnitude of this
      association appears to be modifiable by gender, exogenous estrogens, diet and
      perhaps by body size. The less pronounced associations between the APOE
      polymorphism and high-density lipoprotein (HDL) cholesterol and triglycerides
      appear to differ by gender, to be enhanced by hyperglycemia and alcohol
      consumption, and abolished by exogenous estrogens in women, thus suggesting
      strong context dependency. The APOE polymorphism explains more of the variation
      in levels of cholesterol and apolipoprotein B (APOB) in women than in men,
      whereas a larger fraction of the variation in triglycerides is explained by the
      APOE polymorphism in men than in women. Finally, relative to epsilon 33
      individuals, epsilon 32 women may be protected while epsilon 43 and epsilon 44
      men may be particularly susceptible to ischemic heart disease. In conclusion,
      differences in magnitude or presence of APOE gene associations across studies or
      across subgroups within studies appear to be due to the influence of gender,
      exogenous estrogens, diet, hyperglycemia, alcohol consumption and perhaps body
      size. Consequently, these contexts should be considered when APOE polymorphism is
      studied.

PMID- 11317941
TI  - A cluster of positively charged amino acids in the alpha-chain of C4b-binding
      protein (C4BP) is pivotal for the regulation of the complement system and the
      interaction with bacteria.
AB  - C4b-binding protein (C4BP) is a potent inhibitor of the classical pathway of
      complement. Structural analysis of our 3D model of the C4BP alpha-chain suggested
      that a cluster of positively charged amino acids at the interface between
      complement control protein (CCP) modules 1 and 2 could be involved in ligand
      binding. Nine C4BP mutants, where the positively charged amino acids were changed
      to glutamines, were expressed. We found that all of these displayed lower
      apparent affinity for C4b and that the site was also a specific heparin-binding
      site. The mutants demonstrated decreased ability to serve as factor I cofactors
      in a degradation of C4b. Also, their capacity to prevent the assembly of C3
      convertase and to accelerate its decay were decreased. In conclusion, we found a
      binding site on C4BP that is functionally important for the regulation of C3
      convertase. Many strains of Streptococcus pyogenes bind C4BP, via surface M
      proteins, which plays an important role in pathogenesis. Using the set of C4BP
      mutants we identified a key recognition surface for M proteins which overlaps
      with the C4b-binding site. The analysis of all mutants and inhibition with
      monoclonal antibodies indicated that the binding sites for C4b and M proteins are
      only overlapping but not identical. Furthermore, we found that the molecular
      mechanisms involved in these two interactions differ, since the binding between M
      proteins and C4BP is relatively insensitive to salt in contrast to the C4BP-C4b
      binding. We suggest that binding between C4b and C4BP is governed mostly by
      electrostatic interactions, while additional non-covalent forces cause tight
      binding of C4BP to streptococcal M proteins.

PMID- 11317942
TI  - Characterization and determination of the complex between prostate-specific
      antigen and alpha 1-protease inhibitor in benign and malignant prostatic
      diseases.
AB  - Prostate-specific antigen (PSA) is a tissue-specific serine protease which forms
      complexes with protease inhibitors such as alpha 1-antichymotrypsin and alpha 2
      macroglobulin. We have studied the interaction between PSA and alpha 1-protease
      inhibitor (API) in vitro and found that 15% of the added PSA binds to API while
      the majority of API is cleaved between Met358 and Ser359 when PSA is incubated
      with a 5-fold excess of API at 37 degrees C for 7 days. The complex between PSA
      and API (PSA-API) formed in vitro displays the same chromatographic behavior,
      molecular size and immunoreactivity as endogenous PSA-API occurring in serum,
      indicating that they are identical. PSA-API can be detected in serum by a time
      resolved immunofluorometric assay (IFMA), in which a monoclonal antibody to PSA
      is used as a catcher and a polyclonal antibody to API labeled with a Eu-chelate
      is used as a tracer. Purified PSA-API formed in vitro is used as a calibrator.
      PSA-API in serum represents 1.0-7.9% (median 2.4%) of total PSA (tPSA) in
      prostate cancer (PCa, n = 82) and 1.3-12.2% (median 3.6%, p < 0.01) in patients
      with benign prostatic hyperplasia (BPH, n = 66). The IFMA for PSA-API in serum is
      hampered by a variable background, which is caused by non-specific adsorption of
      the huge excess of API in serum to the solid phase. The background can be
      determined by an assay using the same tracer as in the IFMA for PSA-API but PSA
      unrelated antibody on the solid phase. The background signal is subtracted from
      the PSA-API signal. The clinical utility of PSA-API in serum has been evaluated
      in PSA-positive subjects from the Finnish PCa screening trial. After subtraction
      of the background, the proportion of PSA-API in relation to tPSA is lower in PCa
      than in controls, 0.9% vs. 1.6%, respectively (p < 0.001). Logistic regression
      analysis showed that the concentration of PSA-API was independent of the
      proportion of free PSA as a diagnostic variable among subjects with a tPSA of 4
      10 micrograms/l (p = 0.009). The probability of PCa calculated by logistic
      regression using the concentration of PSA-API and the proportion of free PSA in
      serum significantly improved cancer specificity at high sensitivity levels (85
      95%) as compared to the proportion of free PSA alone.

PMID- 11317943
TI  - Development of novel peptide ligands modulating the enzyme activity of prostate
      specific antigen.
AB  - Prostate-specific antigen (PSA) is a serine proteinase produced mainly by
      epithelial cells of the prostate. Measurement of PSA in serum is widely used for
      diagnosis and monitoring of prostate cancer. The major problem of the PSA
      determination in early diagnosis is the high false positive rate due to benign
      prostatic hyperplasia, but the clinical accuracy can be improved by determining
      the proportions of various molecular forms of PSA. The main biological function
      of PSA is liquefaction of the seminal gel formed after ejaculation, but PSA has
      also been suggested to regulate invasiveness and metastatic potential of
      prostatic tumors. Thus, agents binding to and affecting the function of PSA have
      the potential to be used for diagnosis and therapy of prostate cancer. We have
      developed peptides specific for PSA by using cyclic phage display peptide
      libraries. After deducing the amino acid sequence of the peptides by sequencing
      the relevant part of phage genome, the peptides were expressed as glutathione-S
      transferase (GST) fusion proteins or produced by chemical synthesis. The peptides
      were shown to bind to PSA specifically as indicated by lack of binding to other
      related serine proteinases. The binding of the peptides with PSA was strongly
      inhibited by monoclonal antibodies specific for free PSA and they did not bind to
      PSA-inhibitor complexes indicating that they bind close to the active site of the
      enzyme. Most of the peptides enhanced the enzyme activity of PSA against a
      chromogenic substrate. The affinity of the peptides could be increased by
      including Zn2+ in the reaction mixture. These results show that peptides that
      bind to PSA and modulate its enzyme activity can be developed by phage display
      techniques. These peptides have the potential to be used for targeting of
      prostatic tumors and diagnostics of prostate cancer.

PMID- 11317944
TI  - Process research in understanding and applying psychological therapies.
AB  - OBJECTIVES: Research on the process of psychological therapy aims to demonstrate
      how therapy works, partly to increase understanding, but primarily to increase
      effectiveness by pointing to the crucial ingredients which effect change. This
      paper aims to demonstrate some of the reasons why process research should be
      undertaken in the attempt to increase therapeutic effectiveness. METHODS: A model
      of scientific inquiry suggests three broad types of process research: (1) studies
      which describe behaviours and processes occurring within therapy sessions
      (exploratory studies); (2) studies which investigate the links between specific
      psychotherapy processes and treatment outcome (hypothesis testing); (3) studies
      which examine the links between specific psychotherapy processes and theories of
      change (theory development). Using this typology, we describe key aspects of
      process research: what it is; what has been studied; the limitations of existing
      research. RESULTS: Descriptive studies have deepened understanding of the
      therapeutic process; however, a large number of reliable process-outcome links
      have been hard to establish. Comparative studies have been rare. Studies which
      are linked to models of change and which attempt to track therapist
      responsiveness are more complex and have been more promising. Most studies are
      beset by methodological difficulties. CONCLUSIONS: There are a number of
      promising future research possibilities and methods. Despite methodological
      challenges, the field is developing and research is encouraging. We argue that
      process research has a significant place in advancing our understanding of the
      complexity of therapeutic change, and hence in facilitating theory development
      and effective therapeutic interventions.

PMID- 11317945
TI  - Croatian children's experience of war is not reflected in the size and placement
      of emotive topics in their drawings.
AB  - OBJECTIVES: The claim that topics in children's drawings convey the children's
      emotional attitude towards those topics was investigated. DESIGN: The influence
      of an emotional topic (neutral man, friendly and enemy soldier) and trauma group
      (child with father or father killed in war) was examined on the size of the
      topics and their placement relative to a self-portrait drawing. METHODS: Sixty
      Croatian children drew a man, followed on a separate page by either (a) a
      Croatian soldier, (b) an enemy soldier or (c) a second drawing of a man. The
      child's self-portrait drawing was placed on each page. RESULTS: There were no
      significant main or interaction effects on size or placement of topic.
      CONCLUSIONS: There are unlikely to be reliable features of drawings that portray
      the child's emotional attitude towards the topic drawn.

PMID- 11317946
TI  - Social anxiety and disfigurement: the moderating effects of fear of negative
      evaluation and past experience.
AB  - OBJECTIVES: To examine the relevance of social anxiety and past experience to the
      social and psychological consequences of disfigurement. METHOD: One hundred and
      forty-one patients on the psoriasis register at a dermatology clinic responded to
      a postal survey which was designed to examine the effects of psoriasis on quality
      of life as it was related to clinical severity, level of social anxiety and
      patients' previous experiences of acceptance or rejection. RESULTS: Psoriasis was
      most relevant for quality of life for those patients whose condition was visible
      on their face and hands and who reported a high fear of negative evaluation.
      Current quality of life, fear of negative evaluation and HAD anxiety scores were
      only tentatively related to the nature of previous experiences. CONCLUSIONS:
      Although direction of causality cannot be ascertained from these results, they
      suggest that interventions designed to reduce social anxiety could be used to
      help people who are having difficulty in adjusting to disfiguring medical
      conditions.

PMID- 11317947
TI  - The revised version of the Screen for Child Anxiety Related Emotional Disorders
      (SCARED--R): first evidence for its reliability and validity in a clinical
      sample.
AB  - OBJECTIVES: The Revised version of the Screen for Child Anxiety Related Emotional
      Disorders (SCARED-R) is a 66-item self-report questionnaire that intends to
      measure the entire spectrum of DSM-defined anxiety disorder symptoms in children.
      The current study was a first attempt to examine the reliability and validity of
      the SCARED-R in a clinical setting. METHODS: Forty-eight children (25 children
      with anxiety disorders and 23 children with disruptive disorders) aged between 8
      and 17 years completed the SCARED-R and the Revised Fear Survey Schedule for
      Children at their first visit to an outpatient treatment centre. RESULTS: Results
      showed that in this sample of clinically referred children, the SCARED-R was
      reliable in terms of internal consistency, correlated significantly with an
      alternative measure of childhood anxiety (the Fear Survey Schedule for Children
      Revised), and discriminated well between children with anxiety disorders and
      children with disruptive disorders. CONCLUSIONS: It can be concluded that the
      SCARED-R is a valuable addition to the arsenal of self-report instruments that
      are used for the assessment of childhood anxiety.

PMID- 11317948
TI  - An experimental investigation of thought suppression and anxiety in children.
AB  - OBJECTIVES: This study aimed to explore the effects of thought suppression in
      children--in particular, whether trying to suppress a thought leads to an
      immediate and/or delayed increase in its occurrence. The influence of anxiety on
      children's performance in the experimental paradigm was also examined. DESIGN:
      Participants were allocated to conditions in a between-groups experimental design
      devised on the basis of thought suppression methodologies reported in the adult
      literature. METHODS: One-hundred and twelve participants were recruited from
      local primary schools and randomly allocated to four experimental conditions.
      Children in all conditions monitored the occurrence of a target thought (either
      neutral or anxiety-provoking) by tapping their hand on a table each time the
      thought came to mind during two consecutive experimental periods. During the
      first period, half the children were asked not to think about the target thought,
      while the remaining half were asked to think about anything. During the second
      period, all children were instructed to think about anything. RESULTS: No
      evidence was found for either an immediate or a delayed increase in frequency of
      target thoughts as a consequence of suppression attempts. State and trait anxiety
      were, however, found to influence children's performance during these
      experimental tasks and were associated with increased intrusions under certain
      conditions. CONCLUSIONS: The results of this study suggest that the experimental
      thought suppression paradigm is workable with 7-11-year-old children. The
      methodological, theoretical and clinical implications of these findings are
      discussed.

PMID- 11317949
TI  - Cognitively oriented psychotherapy for early psychosis (COPE): a 1-year follow
      up.
AB  - OBJECTIVES: Cognitively oriented psychotherapy for early psychosis (COPE) is
      aimed at facilitating the adjustment of the person, and at preventing or
      alleviating secondary morbidity in the wake of the first psychotic episode.
      DESIGN: A total of 80 people participated in the initial trial and completed
      assessments on a range of outcome measures. Post-treatment assessment results
      from a non-randomized controlled trial of COPE have been previously reported. The
      present paper describes the results obtained from 51 patients who attended a
      follow-up assessment 1 year subsequent to the end-of-treatment assessment.
      METHOD: The 51 patients formed three groups: (1) those who were offered and
      accepted COPE; (2) those who were offered COPE but refused it, and continued to
      receive other services from the Early Psychosis Prevention and Intervention
      Centre (EPPIC) (refusal subjects); and (3) those who were offered neither COPE
      nor any other continuing treatment from EPPIC (control subjects). RESULTS: At 1
      year follow-up, there was only one significant difference and this was between
      the COPE and refusal groups on the Integration/Sealing Over (I/SO) measure (p =
      .008). End-of-treatment differences were mostly sustained over the 1-year follow
      up period. When the complete sample of 80 was considered, there were no
      differences between the three groups in terms of hospital admissions, community
      episodes, or time taken to first in-patient re-admission. CONCLUSIONS: The study
      was weakened by the poor follow-up rates in the two control groups. This reduced
      power to detect differences between groups on the seven major measures. However,
      the relapse data gathered on the complete set of 80 patients were discouraging
      and suggest that the present formulation of COPE does not confer any advantage to
      those patients receiving the therapy over those not receiving the therapy.

PMID- 11317950
TI  - Simulated malingering in pain patients: a study with the Pain Patient Profile.
AB  - OBJECTIVE: To investigate the utility of the Pain Patient Profile (P3) in
      detecting those who are faking or exaggerating complaints of pain while
      attempting to avoid detection. METHOD: A control group of pain patients ('Pain
      Controls'; PC; N = 62) was compared with a general clinical group who did not
      report pain but were instructed to simulate malingered pain ('General
      Rehabilitation Simulators', GR, N = 34); and a group whose primary problem was
      chronic pain who were instructed to exaggerate the extent of their pain and
      related problems ('Pain Simulators' PS; N = 26). RESULTS: Both groups of
      simulating participants reported significantly higher scores on all clinical
      scales (anxiety, depression, somatization) compared with non-simulating control
      participants and were more likely to obtain an abnormal T-score on the clinical
      scales. The validity scale was able to differentiate the PS group from the PC
      group, but the GR group was not differentiated from the PC group by the validity
      scale. CONCLUSIONS: The results indicate that with further study, the P3 may be a
      useful adjunct to the clinical assessment of symptom magnification in pain
      claimants.

PMID- 11317951
TI  - A randomized controlled trial of the effects of multi-sensory stimulation (MSS)
      for people with dementia.
AB  - OBJECTIVES: To investigate short-term effects of Multi-Sensory Stimulation (MSS)
      on behaviour, mood and cognition of older adults with dementia, the
      generalization of effects to day hospital and home environments and the endurance
      of any effects over time. DESIGN: A randomized controlled trial comparing MSS
      with a credible control of one-to-one activities. METHODS: Fifty patients with
      diagnoses of moderate to severe dementia were randomized to either MSS or
      Activity groups. Patients participated in eight 30-minute sessions over a 4-week
      period. Ratings of behaviour and mood were taken before, during and after
      sessions to investigate immediate effects. Pre, mid, post-trial, and follow-up
      assessments were taken to investigate any generalization of effects on cognition,
      behaviour at the day hospital and behaviour and mood at home and endurance of
      effects once sessions had ceased. RESULTS: Immediately after MSS and Activity
      sessions patients talked more spontaneously, related better to others, did more
      from their own initiative, were less bored/inactive, and were more happy, active
      or alert. Both groups were more attentive to their environment than before, with
      a significantly greater improvement from the MSS group. At the day hospital,
      patients in the Activity group improved on their 'speech skills' (amount of
      speech; initiation of speech), whereas the MSS group remained unchanged during
      the trial. The MSS group showed a significant improvement in mood and behaviour
      at home compared to the Activity group whose behaviour deteriorated. No longer
      term benefits were shown; indeed, behaviour declined sharply during the month
      follow-up period. CONCLUSIONS: Both MSS and Activity sessions appear to be
      effective and appropriate therapies for people with dementia.

PMID- 11317952
TI  - Estimating premorbid IQ from demographic variables: a comparison of a regression
      equation vs. clinical judgement.
AB  - OBJECTIVES: To assess the accuracy with which clinicians estimate premorbid IQ
      from demographic variables and compare it with a regression equation which uses
      the same information. DESIGN: Repeated measures and correlational. METHODS: Sixty
      participants were administered the WAIS-R and had their demographic variables
      recorded (age, sex, years of education and occupation). Eight clinical
      psychologists estimated the participants' IQs from the demographic variables.
      Estimated IQs were also obtained using a regression equation developed by
      Crawford and Allan (1997). RESULTS: The correlation between obtained IQ and the
      equation-based estimate was significantly higher than the correlation between
      obtained IQ and the clinicians' estimates. Further, mean estimated IQ from the
      regression equation did not differ significantly from obtained IQ whereas the
      means for four of the eight clinicians' estimates did differ significantly.
      CONCLUSIONS: Demographic-based regression equations can provide unbiased and
      useful estimates of premorbid IQ; these estimates can be modified in the light of
      the additional qualitative information available to the clinician.

PMID- 11317953
TI  - [Interleukin-10: an anti-atherogenic cytokine].

PMID- 11317954
TI  - Relationship of Staphylococcal isolates in a Moroccan hospital by comparing
      phenotypical and genotypical tests.
AB  - The relationship of Staphylococcus isolates was determined among a collection of
      26 clinical strains at the Centre Hospitalier Universitaire de Rabat. These
      isolates originated principally from blood culture and wounds. In order to affirm
      the clonal origins of these isolates, six phenotype (biotype, anti-biotype,
      serotype, phage type), and genotype (random amplified polymorphic DNA, pulsed
      field gel electrophoresis) methods were used. Biotyping, anti-biotyping, phage
      and serotyping were generally not sufficient while many isolates remained non
      phage typeable. Random amplified polymorphic DNA analysis used in epidemiological
      typing seemed suitable for S. epidermidis and S. haemolyticus. However, rigorous
      standardization will be needed to assure reliable results. Pulsed field gel
      electrophoresis discriminated more efficiently than random amplification
      polymorphic DNA analysis. This study attests to the suitability of two or more
      methods in combination for typing Staphylococcus isolates.

PMID- 11317955
TI  - [Expression of p21 WAF1/CIP1 protein in colorectal cancers: study of its relation
      to p53 mutation and Ki67 antigen expression].
AB  - Mutations of the p53 gene are the most common genetic alteration in malignant
      human tumors. A cyclin-dependent kinase inhibitor, p21WAF1/CIP1, is thought to be
      an important mediator of p53-induced cell cycle arrest. Although numerous studies
      have reported p53 expression and mutation in colorectal cancer few of them have
      correlated p53 expression with that of its downstream effector p21 and with the
      proliferation index as measured by expression of the Ki67 nuclear antigen. We
      studied p53, p21 and Ki67 expression by immunohistochemistry and molecular
      biology in 35 colorectal carcinomas. We compared these findings with each other
      and with clinical factors. Sixty three percent of tumors expressed p53 whereas
      seventy one percent expressed p21WAF1/CIP1. In adenocarcinomas, p21 staining was
      heterogeneous: p21-reactive cells were seen in the most differentiated areas.
      There was no correlation between p21WAF1/CIP1 and p53 expression, p53 mutation,
      Ki67 expression or clinical factors such as sex or location of the tumor. On the
      other hand, there was a statistical relationship between p21 expression and
      survival: our results indicated an association between high p21 expression and
      lower stages p21WAF1/CIP1 appears to be induced independently of p53 in these
      tumors and may be associated with differentiation rather than proliferation.

PMID- 11317956
TI  - [Apropos of a case of Streptococcus pneumoniae salpingitis, epidemiology of
      female genital pneumococcal infections].
AB  - BACKGROUND: Pneumoccocci were sometimes isolated from female genital tract
      specimens, usually without any clinical signification. However few cases of
      female pneumococcal genital infections were previously reported. CASE REPORT: We
      describe an additional report of salpingitis, occurring in a 35-years old female
      early after installation of an intra-uterine device. DISCUSSION: Data collected
      by the National Reference Center for Pneumococci show that 0.9% of the strains
      documented in the past five years (1992 to 1996) were isolated from the female
      genitals tract. Most of these infections are caused by S. pneumoniae belonging to
      the serotypes 1 or 3. About 20% of the strains displayed a reduced sensitivity to
      penicillin. Although genital infections caused by S. pneumoniae and the neonatal
      colonisation with the maternal strain are rare, their potential occurrence should
      not be neglected. Thus, in order to limit the risks of such infections, an
      antibiotic treatment should immediately started following the detection of a
      pneumococcal genital carriage.

PMID- 11317957
TI  - [Contribution of the laboratory to the epidemiologic study of bacterial
      infections].
AB  - The laboratory plays a significant role in the epidemiologic investigations by
      the comparative analysis of the bacterial strains involved in the outbreaks.
      Recently, the use of molecular analysis methods provided better performance than
      traditional phenotypic methods which are still used as preliminary tests because
      of their relatively low cost and technical simplicity. These analyses deal with
      either the whole chromosome of the bacterium, plasmids or particular genes. The
      classification of these methods runs up against the lack of consensus concerning
      their nomenclature. A clearer denomination based upon the technique responsible
      for revealing the polymorphisms of these various targets, makes it possible to
      divide these methods in two principal groups: methods of RFLP (based on the
      fragments resulting from digestion with restriction enzymes) and methods of AFLP
      (based on the products of amplification by PCR). The knowledge of the typability
      of the strains and the qualities of these various methods, particularly their
      discriminatory power, is essential to the accuracy of the laboratory analysis in
      the investigations of outbreaks.

PMID- 11317958
TI  - Myeloproliferative syndromes. Current opinions from the European Hematology
      Association Working Group on Myeloproliferative Disorders.

PMID- 11317959
TI  - Clinicopathology and histochemistry on bone marrow biopsies in chronic
      myeloproliferative disorders--a clue to diagnosis and classification.
AB  - A clinicopathological study was carried out to address the currently still
      controversial issues of: 1) thrombocythaemias in chronic myeloproliferative
      disorders (MPDs); 2) Initial, prefibrotic idiopathic myelofibrosis (IMF); 3)
      discrimination of spurious polycythaemic states or polyglobuly (PG) from
      polycythaemia vera (PV); 4) unclassifiable MPDs. Based on a synoptical approach
      which implicates a comparative evaluation of laboratory data and histopathology
      of the bone marrow, the discriminating efficiency of both diagnostic tools has
      been emphasized. An elaborate evaluation of histotopography and cytological
      appearance of megakaryopoiesis is an invaluable aid to distinguish the different
      subtypes of MPDs which may eventually present with a significant elevation of the
      platelet count. Prefibrotic IMF is not only associated with a certain set of
      clinical symptoms (minimal to slight anaemia, splenomegaly, thrombocytosis), but
      should also be characterized by specific alterations of bone marrow morphology.
      Moreover, follow-up studies are in keeping with the finding that these patients
      evolve into typical IMF regarding laboratory parameters and ensuing
      myelofibrosis. Smokers polycythaemia--PG may be separated from early PV by the
      significant raise in the red cell mass and also by a few, easily determinable
      clinical parameters (i.e. EPO level, thrombocytosis, LAP). Both conditions can be
      distinguished by regarding bone marrow features (megakaryopoiesis, interstitial
      changes) which exert a distinctive impact. According to our experience the
      majority of patients categorized as unclassifiable MPDs include cases in which
      clinical or morphological data are inadequate to permit a more precise diagnosis.
      Only in a small proportion not a failing methodology, but initial stages of the
      disease process requires sequential examinations to reach a correct diagnosis.

PMID- 11317960
TI  - Prognostic factors and current practice in treatment of myelofibrosis with
      myeloid metaplasia: an update anno 2000.
AB  - Median survival of patients with myelofibrosis with myeloid metaplasia (MMM)
      ranges from 3.5 to 5 years, but there is a wide variability. The degree of anemia
      (Hb < 10 g/dL) is the most important prognostic factor, followed by
      constitutional symptoms and abnormal karyotype. In recent years, different
      prognostic scoring systems for MMM have been proposed. In some of them three
      prognostic groups (low, intermediate, and high risk) are recognized, while others
      recognize a high and a low-risk group only. Median survival of the low-risk group
      ranges from seven to nine years, while the minority of high-risk patients survive
      for a median of less than two years. Younger patients with MMM survive longer
      (median survival above ten years). Among the latter patients, based on Hb value,
      constitutional symptoms, and blood blast-cell percentage, two prognostic groups
      can also be identified, with median survival of less than three years and almost
      15 years, respectively. Conventional treatment of MMM is mostly palliative and
      based on cytolytic treatment (usually hydroxyurea), androgen therapy and
      splenectomy in selected patients. Allogeneic hemopoietic transplant is a
      therapeutic possibility with the potential for cure in younger patients with bad
      prognostic features. The role in MMM of newer treatment strategies such as
      autologous transplantation or the administration of anti-angiogenic drugs such as
      thalidomide is currently being evaluated.

PMID- 11317961
TI  - Involvement of the fibrogenic cytokines, TGF-beta and bFGF, in the pathogenesis
      of idiopathic myelofibrosis.
AB  - Idiopathic Myelofibrosis (IMF), is a chronic myeloproliferative disorder
      characterized by the association of myeloproliferation and myelofibrosis. The
      pathophysiological mechanisms resulting in this disease remain still unclear. The
      myeloproliferation appeared to result from the clonal amplification of
      hematopoietic progenitors. In contrast, fibroblasts participating in
      myelofibrosis were shown to be polyclonal, thus suggesting that myelofibrosis was
      a reactive process. We studied the role of two growth factors TGF-beta and bFGF,
      which display potent fibrogenic properties and are major regulators of primitive
      hematopoiesis, in IMF pathogenesis. We demonstrated an increase of TGF-beta and
      bFGF expression in circulating megakaryocytic cells and platelets, together with
      alterations of the expression of these cytokines and their receptors in
      hematopoietic CD34+ progenitor cells from IMF patients. Our results suggested
      that TGF-beta and bFGF are involved both in myelofibrosis and myeloproliferation
      which characterize IMF.

PMID- 11317962
TI  - [Hydroxyurea--is it a harmless drug in Vaquez disease?]].
AB  - The frequent side effects of Hydroxy-Urea and the non-exceptional risk of
      leukemia and cancer in Polycythemia Vera treated for a long time by Hydroxy-Urea
      allow to conclude that Hydroxy-Urea is not an innocent drug. In a prospective
      trial of 150 patients with a median follow up of nine years, Hydroxy-Urea given
      alone induced side effects in 29% of patients necessitating to stop treatment in
      half of cases. The percentage of leukemia or myelodysplasia is 6.7% with an
      actuarial risk of leukemic transformation of 10% at 13 years. In an other
      prospective trial in 181 aged patients Hydroxy-Urea was given as maintenance
      therapy after 32P treatment. The median follow-up in that study is also of nine
      years. Side effects are observed in 13% of cases. A two fold increase of the
      leukemic risk was observed in the maintenance arm of the trial: 11 versus 19% at
      ten years, 14 vs 30% at 12 years, 16 vs 35% at 15 years because of the
      leukemogenic effect of Hydroxy-Urea in maintenance therapy we stopped including
      new patients in this arm of the trial.

PMID- 11317963
TI  - Epidemiology of the myeloproliferative disorders: essential thrombocythaemia,
      polycythaemia vera and idiopathic myelofibrosis.
AB  - As to the epidemiology of myeloproliferative disorders (MPD) very little solid
      information is available in the literature. The present work attempted to study
      the incidence of MPD in the city of Goteborg, Sweden during a period of ten
      years. Therefore, retrospectively we assessed the number of subjects afflicted
      with polycythaemia vera (PV), essential thrombocythaemia (ET) and idiopathic
      myelofibrosis (IM) over the study period of 1983-1992. The yearly calculated
      incidence for PV was 2.8 per 100,000 population. For ET and IM the corresponding
      figures were 1.5 and 0.4, respectively. The results for PV demonstrated the
      highest incidence rate reported in literature so far. As to ET and IM our results
      largely agree with what has been reported previously in the literature.

PMID- 11317964
TI  - Efficacy and safety of hydroxyurea in patients with essential thrombocythemia.
AB  - Hydroxy-urea has emerged as the treatment of choice in patients with essential
      thrombocythemia and an high risk of thrombosis because of its efficacy and only
      rare acute toxicity. However, there is some concern regarding the potential role
      of this drug in enhancing the risk of leukemic transformation. This risk suggests
      not to use hydroxyurea in young patients at low-risk for thrombosis. In these
      cases, major or fatal vascular occlusive complications are rare, and no data are
      available on the effectiveness of HU in reducing this rate. Sequential multiple
      chemotherapy, such busulphan followed by HU, should be avoided in any case
      because of the high risk of secondary leukemias.

PMID- 11317965
TI  - Idiopathic erythrocytosis, diagnosis and clinical management.
AB  - By definition, idiopathic erythrocytosis (IE) applies to a group of patients
      characterised by having a measured RCM above their predicted normal range (an
      absolute erythrocytosis) and following investigation do not have a form of
      primary or secondary erythrocytosis. Patients with IE are heterogenous. The
      possibilities include physiological variation, 'early' polycythaemia vera (10-15%
      develop clear features of PV over a few years), unrecognized congenital
      erythrocytosis, unrecognized or unrecognizable secondary acquired erythrocytosis
      or a currently undescribed form of primary or secondary erythrocytosis. Patients
      are more commonly male with a median age at presentation of 55-60 years.
      Approximately half of the patients present with vascular occlusive complications.
      Retrospective evidence indicates that vascular occlusion occurs less frequently
      when the PCV is controlled at normal levels. Venesection is the treatment of
      choice to lower the PCV. As a general approach to management, all patients with a
      PCV above 0.54 should be venesected to a PCV less than 0.45. This target PCV
      should also apply to patients with lesser degrees of raised PCV who have
      additional other risk factors for vascular occlusion.

PMID- 11317966
TI  - Management of patients with essential thrombocythemia: current concepts and
      perspectives.
AB  - Essential thrombocythemia must now be regarded as a heterogeneous disease. Recent
      availability of clonality studies have repeatedly shown that a significant number
      of female patients diagnosed as E.T. according the most stringent criteria had a
      definitely polyclonal myelopoiesis. Although the incidence of patients newly
      diagnosed every year is low, there is in fact a conspicuous population of E.T.,
      followed as outpatients in every department of hematology or internal medicine,
      including a large number of young females. These eventualities should be
      integrated in further discussions of the benefit/risk ratio of cytoreduction with
      the presently available drugs. The combination of several evidence-based data is
      the basis of a widely accepted stratification of high-risk patients defined by
      any of the following features. Age > 60 to 65. History of thrombosis or embolic
      or major ischemic events. Platelet counts in excess of 1000 or 1500 x 10(9)/L. In
      the question of chemotherapy in E.T., growing concern comes from the potential
      leukemogenic risk associated with the presently available drugs and extends
      beyond Melphalan, Busulfan and other alkylating agents and includes non
      alkylating agents like Hydroxyurea. At the same time, much attention has been
      paid to the introduction of very precise initial diagnostic criteria directed to
      elimination of other myeloproliferative or myelodysplastic disorders with an
      increased risk of transformation. Present treatment of E.T. is a compromise
      between prevention of E.T. related thrombotic and bleeding complications on one
      hand and long term side effects and toxicity of the presently available drugs on
      the other hand. The recent availability of non mutagenic drugs like Interferon
      and most of all Anagrelide; the recognition of the role of antiaggregating agents
      in the treatment of platelet related microvascular ischemic events gives the
      opportunity for further comparative prospective trials. The use of aspirin in the
      management of pregnant E.T. patients is now widely accepted but there is still
      controversies concerning the use of Interferon in this situation.

PMID- 11317967
TI  - [Effects of water use conditions on cancer morbidity].
AB  - The study demonstrated that the cancer situation is tense in the Tsimlyansk area
      and it can be referred to a high malignant tumor morbidity and mortality zone.
      The sources of water supply of populated localities may be involved in the
      formation of malignant tumor morbidity rates.

PMID- 11317968
TI  - [Immunological changes in dust-induced lung diseases].
AB  - One hundred and forty five patients with different forms of dust-induced lung
      disease and 57 controls having no contacts with industrial aerosols were
      examined. It was ascertained that clinical and functional evidence cannot predict
      the course of the disease and the development of infectious complications
      (silicotuberculosis, mechanic bronchitis). Impaired humoral immunity and
      nonspecific resistance in dust-induced lung disease depend on the type of disease
      and predispose to infectious complications. Predisposition to occupational lung
      diseases (pneumoconioses, mechanical bronchitis) is associated with increases in
      the concentrations of plasma fibronectin and serum IgA and a decrease in serum
      mucin antigen levels. In chronic mechanical bronchitis, there were lower
      activities of lysozyme and complement and elevated serum IgM and IgG
      concentrations. Fibronectin, total IgE and the inflammatory marker the mucin
      antigen 3EG5 are involved in immunological inflammation in dust-induced lung
      disease. It is worth of determining the factors of humoral immunity and
      nonspecific resistance in workers contacting with high concentrations of
      industrial aerosols and in patients with dust-induced diseases to make a precise
      assessment of the time course of changes in a pathological process and to define
      a risk for infectious complications.

PMID- 11317969
TI  - [Changes in the functional state of the nervous system of students during
      studies].
AB  - The paper describes the function of the autonomic nervous system of students
      during their study at a higher educational establishment. There are changes in
      the activity of the sympathetic and parasympathetic nervous system during a study
      day and examination session. Findings indicate that the examination session is a
      strong stress to the students, which appears as significant rises in the higher
      tension index and in the Kerdo autonomic index and a reduction in the standard
      deviation of cardiac intervals.

PMID- 11317970
TI  - [Use of Bifidobacterium-containing therapeutic dietetic food products in the
      prevention of dysbacteriosis].

PMID- 11317971
TI  - [Results of a sociological survey of human nutrition in Kemerovo city].

PMID- 11317972
TI  - Renal homotransplantation in identical twins. 1955.

PMID- 11317973
TI  - Training overseas doctors in the United Kingdom. Promoting opportunities helps to
      promote British healthcare values.

PMID- 11317974
TI  - Lumbar sagittal contour after posterior interbody fusion: threaded devices alone
      versus vertical cages plus posterior instrumentation.
AB  - STUDY DESIGN: An observational radiographic study examining lumbar sagittal
      contour of patients undergoing posterior interbody arthrodesis. OBJECTIVES: To
      compare operative alterations of lumbar sagittal contour after posterior
      interbody fusion using threaded interbody devices alone versus vertical cages
      combined with posterior compression instrumentation. SUMMARY OF BACKGROUND DATA:
      Technique-related alterations of lumbar sagittal contour during interbody
      arthrodesis have received little attention in the spinal literature. METHODS:
      Standing lumbar radiographs were measured for preoperative and postoperative
      segmental lordosis at levels undergoing posterior interbody arthrodesis using
      either stand-alone side-by-side threaded devices or vertical cages combined with
      posterior transpedicular compression instrumentation. Sagittal plane segmental
      correction (or loss of correction) was calculated and statistically compared.
      RESULTS: The radiographs of 30 patients (34 spinal segments) undergoing lumbar or
      lumbosacral arthrodesis were compared. Seventeen patients (18 segments) had
      undergone interbody fusion using threaded cages,whereas 13 patients (16 segments)
      underwent fusion using vertically oriented mesh cages combined with posterior
      compression instrumentation. Preoperative segmental lordosis averaged 8 degrees
      for both groups. For patients undergoing fusion with threaded cages, there was a
      mean lordotic loss of 3 degrees/segment. For patients undergoing fusion with
      vertically oriented mesh cages combined with posterior compression
      instrumentation,there was a mean lordotic gain of 5 degrees/segment. This
      difference in segmental sagittal plane contour was highly significant (P = 0.00).
      CONCLUSION: Threaded fusion devices placed under interbody distraction with the
      endplates parallel fail to preserve or reestablish segmental lordosis. Vertical
      cages, however, when combined with posterior compression instrumentation, not
      only maintain segmental lordosis, but also can correct sagittal plane deformity.

PMID- 11317975
TI  - Toxic Inheritance: fathers' job may mean cancer for kids.

PMID- 11317976
TI  - Weathering diarrheal illness: effects of El Nino in the South Pacific.

PMID- 11317977
TI  - Home-cooked pesticides: consumption varies by season.

PMID- 11317978
TI  - New antimicrobial agents approved by U.S Food and Drug Administration in 2000 and
      new indication for previously approved agents.

PMID- 11317980
TI  - [The 74th annual meeting of the Japanese Society for Bacteriology. Okayama,
      Japan. April 2-4, 2001. Abstracts].

PMID- 11317979
TI  - How big is a bacterium? Approximation to a correct total cell density of
      Arthrobacter sp.

PMID- 11317981
TI  - [89th annual meeting of the Japanese Urological Association. Kobe, Japan. April
      14-17, 2001. Abstracts].

PMID- 11317982
TI  - Fixed-time schedule effects as a function of baseline reinforcement rate.
AB  - Using an arbitrary response, we evaluated fixed-time (FT) schedules that were
      either similar or dissimilar to a baseline (response-dependent) reinforcement
      schedule and extinction. Results suggested that both FT schedules and extinction
      resulted in decreased responding. However, FT schedules were more effective in
      reducing response rates if the FT reinforcer rate was dissimilar to baseline
      reinforcer rates. Possible reasons for this difference were evaluated with data
      analysis methods designed to identify adventitious response-reinforcer relations.

PMID- 11317984
TI  - Behavioral cusps: a model for selecting target behaviors.

PMID- 11317983
TI  - Temporal discounting: basic research and the analysis of socially important
      behavior.
AB  - Recent basic research on human temporal discounting is reviewed to illustrate
      procedures, summarize key findings, and draw parallels with both nonhuman animal
      research and conceptual writings on self-control. Lessons derived from this
      research are then applied to the challenge of analyzing socially important
      behaviors such as drug abuse, eating and exercise, and impulsiveness associated
      with attention deficit hyperactivity disorder. Attending to the broader temporal
      context in which behavior occurs may aid in the analysis of socially important
      behavior. Applying this perspective to the study of behavior in natural
      environments also highlights the importance of combining methodological
      flexibility with conceptual rigor to promote the extension of applied behavior
      analysis to a broader array of socially important behaviors.

PMID- 11317985
TI  - Reinforcement schedule thinning following treatment with functional communication
      training.
AB  - We evaluated four methods for increasing the practicality of functional
      communication training (FCT) by decreasing the frequency of reinforcement for
      alternative behavior. Three participants whose problem behaviors were maintained
      by positive reinforcement were treated successfully with FCT in which
      reinforcement for alternative behavior was initially delivered on fixed-ratio
      (FR) 1 schedules. One participant was then exposed to increasing delays to
      reinforcement under FR 1, a graduated fixed-interval (FI) schedule, and a
      graduated multiple-schedule arrangement in which signaled periods of
      reinforcement and extinction were alternated. Results showed that (a) increasing
      delays resulted in extinction of the alternative behavior, (b) the FI schedule
      produced undesirably high rates of the alternative behavior, and (c) the multiple
      schedule resulted in moderate and stable levels of the alternative behavior as
      the duration of the extinction component was increased. The other 2 participants
      were exposed to graduated mixed-schedule (unsignaled alternation between
      reinforcement and extinction components) and multiple-schedule (signaled
      alternation between reinforcement and extinction components) arrangements in
      which the durations of the reinforcement and extinction components were modified.
      Results obtained for these 2 participants indicated that the use of
      discriminative stimuli in the multiple schedule facilitated reinforcement
      schedule thinning. Upon completion of treatment, problem behavior remained low
      (or at zero), whereas alternative behavior was maintained as well as
      differentiated during a multiple-schedule arrangement consisting of a 4-min
      extinction period followed by a 1-min reinforcement period.

PMID- 11317986
TI  - A technology to measure multiple driving behaviors without self-report or
      participant reactivity.
AB  - An in-vehicle information system (IVIS) was used to videotape drivers (N = 61)
      without their knowledge while driving 22 miles in normal traffic. The drivers
      were told that they were participating in a study of direction following and map
      reading. Two data-coding procedures were used to analyze videotapes. Safety
      related behaviors were counted during consecutive 15-s intervals of a driving
      trial, and the occurrence of certain safety-related behaviors was assessed under
      critical conditions. These two methods of data coding were assessed for
      practicality, reliability, and sensitivity. Interobserver agreement for the five
      different driving behaviors ranged from 85% to 95%. Within-subject variability in
      safe driving was more pronounced among younger drivers and decreased as a
      function of age. Contrary to previous research that has relied on self-reports,
      driver risk taking did not vary significantly as a function of gender. These
      results are used to illustrate the capabilities of the technology introduced here
      to design and evaluate behavior-analytic interventions to increase safe driving.

PMID- 11317987
TI  - A brief computer-based assessment of reinforcer dimensions affecting choice.
AB  - In an extension of Neef, Shade, and Miller (1994), we used a brief computer-based
      assessment of differential responsiveness to reinforcer rate, quality, delay, and
      response effort in affecting the choices of 11 participants. The assessment
      involved successive presentations of two concurrent sets of math problems, each
      set associated with competing reinforcer or response dimensions in a
      counterbalanced fashion. The results showed that the reinforcer and response
      dimensions differentially affected choice, with time-allocation patterns varying
      across students.

PMID- 11317988
TI  - Analysis of response class hierarchies with attention-maintained problem
      behaviors.
AB  - We replicated a method for clarifying inconclusive functional analysis outcomes
      via an extinction analysis of separate topographies of problem behavior with 2
      participants. Results suggested that both mild and severe problem behaviors
      belonged to the same response class. An analysis of response latency was
      consistent with a response class hierarchy hypothesis, indicating that mild
      problem behavior nearly always occurred prior to severe topographies of problem
      behavior.

PMID- 11317989
TI  - Brief functional analysis and treatment of bizarre vocalizations in an adult with
      schizophrenia.
AB  - Variables responsible for the maintenance of bizarre vocalizations emitted by an
      adult diagnosed with schizophrenia were examined via a brief functional analysis,
      and results suggested that the behavior was maintained by attention. A treatment
      consisting of extinction and differential reinforcement of appropriate
      vocalizations was effective in reducing bizarre vocalizations and increasing
      appropriate vocalizations. The use of functional analysis methodology to examine
      variables that maintain problem behavior in this population is discussed.

PMID- 11317990
TI  - Putative behavioral history effects and aggression maintained by escape from
      therapists.
AB  - Differentially higher rates of aggression in treatment sessions occurred in the
      presence of two staff members who had previously worked with the participant at
      another facility. Adding an edible reinforcer for compliance and the absence of
      aggression in sessions conducted by these two staff members decreased aggression
      to rates similar to those obtained with less familiar therapists. Results suggest
      that embedding positive reinforcement within a demand context may reduce the
      aversiveness of therapists correlated with a history of demand situations.

PMID- 11317991
TI  - Response efficiency during functional communication training: effects of effort
      on response allocation.
AB  - An analogue functional analysis revealed that the problem behavior of a young
      child with developmental delays was maintained by positive reinforcement. A
      concurrent-schedule procedure was then used to vary the amount of effort required
      to emit mands. Results suggested that response effort can be an important
      variable when developing effective functional communication training programs.

PMID- 11317992
TI  - Evaluation of an awareness enhancement device for the treatment of thumb sucking
      in children.
AB  - An evaluation of the awareness enhancement device (AED) described by Rapp,
      Miltenberger, and Long (1998) was conducted with 2 children who engaged in thumb
      sucking past the age at which it was developmentally appropriate. The AED
      effectively suppressed thumb sucking for both children. Future research
      evaluating the AED is discussed.

PMID- 11317993
TI  - Teaching children with autism to engage in conversational exchanges: script
      fading with embedded textual stimuli.
AB  - A multiple baseline across three sets of stimuli was used to assess the effects
      of a script-fading procedure using embedded text to teach 2 children with autism
      to engage in conversation statements about the stimuli. Both students stated all
      the scripted statements, and unscripted statements also increased. Generalization
      was assessed with novel peers and with untrained stimuli.

PMID- 11317994
TI  - Effects of social proximity on multiple aggressive behaviors.
AB  - We systematically manipulated social proximity to examine its influence on
      multiple topographies of aggression. Aggression occurred at high levels during
      close-proximity sessions and at low levels during distant-proximity sessions even
      though social contact was presented continuously during both conditions.
      Topographies of aggression emerged sequentially across the close-proximity
      sessions, and all topographies were reduced to zero following extended sessions
      of this condition.

PMID- 11317995
TI  - Treating aerophagia with contingent physical guidance.
AB  - Contingent physical guidance was used to treat chronic aerophagia. This consisted
      of guiding the participant's hand over her mouth following each attempt to engage
      in aerophagia. A wristwatch was then correlated with the contingent physical
      guidance procedure. Responding remained low in the presence of the wristwatch,
      even after contingent physical guidance was withdrawn.

PMID- 11317996
TI  - Use of a multicomponent treatment for food refusal.
AB  - We examined the use of a multicomponent treatment for food refusal exhibited by a
      5-year-old boy who had been diagnosed with mild to moderate mental retardation.
      Treatment consisted of access to highly preferred tangible items, which were
      removed contingent on problem behavior or not accepting a bite, and differential
      reinforcement of alternative behavior. Treatment resulted in an increase in food
      acceptance to 100% of bite offers and near-zero rates of problem behavior. In
      addition, the participant's caregivers were successfully trained to implement the
      treatment.

PMID- 11317997
TI  - Treatment of multiply controlled destructive behavior with food reinforcement.
AB  - We evaluated the extent to which the positive reinforcement of communication
      would reduce multiply controlled destructive behavior in the absence of relevant
      extinction components. When edible reinforcement for appropriate communication
      and nonfood reinforcers for problem behavior were available simultaneously,
      responding was allocated almost exclusively toward the behavior that produced
      edible reinforcement.

PMID- 11317998
TI  - Effect of corneal polarization axis on assessment of retinal nerve fiber layer on
      thickness by scanning laser polarimetry.

PMID- 11317999
TI  - Consumer demand in the purchase and prescription of sugar-free medicines.
AB  - OBJECTIVES: To determine the current level of consumer demand in the purchase and
      prescription of sugar-free paediatric medicines. DESIGN: Data were collected by
      administered questionnaire. SETTING: The study was conducted in a Hospital
      Paediatric Dentistry Unit and a Community Dental Clinic, both within the Bro Taf
      area of south-east Wales. SAMPLE AND METHODS: The parents of 240 children
      attending for routine dental care responded to one of two short questionnaires,
      depending on whether their child had received a liquid oral medicine in the
      preceding month. RESULTS: Although aware of the benefits of sugar-free medicines,
      parents did not appear to be attempting to exercise the power of consumer demand
      to its full potential. They were more likely to ask a pharmacist (or pharmacist's
      assistant) than their general medical practitioner for a sugar-free medicine.
      CONCLUSIONS: We must continue to promote sugar-free medicines. While increasing
      the importance that health professionals attach to such products, future
      campaigns should also aim to increase consumer demand.

PMID- 11318000
TI  - Polyols in confectionery: the route to sugar-free, reduced sugar and reduced
      calorie confectionery.
AB  - Polyol-containing confectionery offers considerable advantages over traditional
      sucrose-based confectionery in terms of reduced energy content and reduced
      cariogenicity. However, over-consumption of polyol confectionery may lead to
      gastrointestinal symptoms in some individuals. Rather than consider this as a
      distinct disadvantage to the consumer, this article discusses how careful
      consideration of the physico-chemical properties of polyols and advances in
      product development and formulation can provide suitable polyol-based products
      for the consumer. Furthermore. food legislation and ingredient pricing issues are
      just some of the factors that must be taken into account when designing new
      polyol-containing products if their functional benefits and good product quality
      are to be delivered to the consumer.

PMID- 11318001
TI  - Does the platelet-activating factor affect the antioxidant defense system? The
      possible role of hyperbaric oxygenation.
AB  - The platelet-activating factor (PAF) is an inflammatory mediator and it may exert
      some of its effects by reactive oxygen species (ROS). We investigated the effects
      of PAF and hyperbaric oxygenation (HBO) on copper (Cu) and zinc (Zn) levels in
      plasma and the intracellular antioxidant enzyme activities of rats. PAF
      administration caused a decrease in erythrocyte catalase (CAT) and glutathione
      peroxidase (GPx) activities and in the plasma zinc level. Following PAF
      administration, exposure to HBO also caused a decrease in erythrocyte GPx
      activity. These results support the hypothesis that PAF may produce free oxygen
      radicals and HBO enhances this effect. The enzyme activities of the antioxidant
      defense system were found to be affected by these oxidative processes. This is
      likely to be the result of excessive production of ROS or overutilization and/or
      inhibition of the antioxidant enzymes.

PMID- 11318002
TI  - Dental anesthetic procedures for cleft lip and palate patients.
AB  - Many dentists refuse to offer dental assistance to cleft lip and palate patients
      because they lack understanding about this malformation and do not want to make a
      professional mistake with the anesthesia. The aim of this work is to guide
      clinical practitioners, who want to work with these patients about the anatomical
      features of the cleft lip and palate area and the implications in the anesthetic
      procedures.

PMID- 11318003
TI  - Arrangement of the orbicularis oris muscle in different types of cleft lips.
AB  - A thorough knowledge of the anatomy of the labial region, especially the
      arrangement of the muscle fibers, is essential for the success of primary repair
      of the cleft lip. Pared lateral and medial edges from 20 unilateral incomplete
      cleft lips and 25 unilateral complete cleft lips were obtained during primary
      surgery. Three specimens of normal lips were taken from unclaimed infant cadavers
      as the controls. They were prepared for routine histological studies and were
      examined to study the direction of muscle fibers. Intrinsic and extrinsic bundles
      were identified in both lateral and medial sides of specimens of both cleft
      types. The intrinsic bundle was not displaced but was interrupted by the cleft.
      The extrinsic bundle in the lateral side of both cleft types ran upward along the
      lateral cleft margin, whereas in the medial side it ran horizontally to terminate
      close to the medial cleft margin. The extrinsic bundle is the retractor, which is
      associated with facial expression, whereas the intrinsic bundle is the
      constrictor of the mouth. Because there are two functional components in the
      orbicularis oris muscle, identifying and repairing them separately will enable
      each of them to accomplish their distinctive functions.

PMID- 11318004
TI  - Caries preventive knowledge and practices among dental hygienists.
AB  - PURPOSE: The aim of this study was to determine the knowledge, opinions, and
      practices of dental hygienists in the areas of dental caries etiology and
      prevention. METHODS: A pretested, validated 35-question survey instrument was
      mailed to a one percent national, stratified random sample of dental hygienists
      in the United States (n = 960) in October 1996. Four complete mailings of the
      instrument resulted in a 67% response rate, of which 77% were useable (n = 498).
      Respondents were asked if they agreed or disagreed with statements on caries
      etiology and preventive procedures, and also asked to rate the effectiveness of
      procedures for preventing dental caries in children and adults. Data were
      analyzed using descriptive statistics, t-tests, and ANOVA. RESULTS: Overall level
      of knowledge of caries etiology and preventive procedures was low. More than 40%
      of subjects did not recognize that remineralization is the most important
      mechanism of action of fluoride, and fewer than 50% recognized that dental caries
      is a chronic infectious disease. Analysis of four factors thought to be related
      to knowledge and practice showed that younger graduates, more recent graduates,
      and ADHA members were more knowledgeable about the effectiveness of caries
      preventive procedures for children (p < .01). Although an overwhelming majority
      correctly agreed that adults benefit from fluoride and that root caries is an
      emerging problem, this knowledge was inconsistent with practice (p = .02). Fewer
      than 35% reported that they provide fluoride to adults of any age, or they wait
      until the disease is present. For children and adults who did receive fluoride
      treatments, a one-minute application of an APF gel or foam was most often
      provided. CONCLUSIONS: Correct information about the etiology and prevention of
      dental caries is a predisposing factor to making informed decisions. Overall,
      respondents overrated the effectiveness of flossing and toothbrushing while
      underrating the effectiveness of fluorides. In the majority of cases, efficiency
      rather than efficacy was given priority when providing a topical fluoride
      treatment. An improved understanding of dental caries etiology and the scientific
      evidence for appropriate caries preventive procedures will allow dental
      hygienists to prevent and manage this disease better.

PMID- 11318005
TI  - Prone positioning and inhaled nitric oxide: synergistic therapies for acute
      respiratory distress syndrome.
AB  - BACKGROUND: Inhaled nitric oxide (INO) and prone positioning have both been
      advocated as methods to improve oxygenation in patients with acute respiratory
      distress syndrome (ARDS). This study was designed to evaluate the relative
      contributions of INO and prone positioning alone and in combination on gas
      exchange in trauma patients with ARDS. METHODS: Sixteen patients meeting the
      consensus definition of ARDS were studied. Patients received mechanical
      ventilation in the supine position, mechanical ventilation plus INO at 1 part per
      million in the supine position, mechanical ventilation in the PP, and mechanical
      ventilation in the prone positioning plus INO at 1 part per million. A
      stabilization period of 1 hour was allowed at each condition. After
      stabilization,hemodynamic and gas exchange variables were measured. RESULTS: INO
      and prone positioning both increased PaO2/FIO2 compared with ventilation in the
      supine position. PaO2/FIO2 increased by 14% during use of INO, and 10 of 16
      patients (62%) responded to INO in the supine position. PaO2/FIO2 increased by
      33%, and 14 of 16 patients (87.5%) responded to the prone position. The
      combination of INO and prone positioning resulted in an improvement in PaO2/FIO2
      in 15 of 16 patients(94%), with a mean increase in PaO2/FIO2 of 59%. Pulmonary
      vascular resistance was reduced during use of INO, with a greater reduction in
      pulmonary vascular resistance seen with INO plus prone positioning (175 +/- 36
      dynes x s/cm5 vs. 134 +/- 28 dynes x s/cm5) compared with INO in the supine
      position (164 +/- 48 dynes x s/cm5 vs.138 +/- 44 dynes x s/cm5). There were no
      significant hemodynamic effects of INO or prone positioning and no complications
      were seen during this relative short duration of study. CONCLUSIONS: INO and
      prone positioning can contribute to improved oxygenation in patients with ARDS.
      The two therapies in combination are synergistic and may be important adjuncts to
      mechanical ventilation in the ARDS patient with refractory hypoxemia.

PMID- 11318006
TI  - A disease-specific activity index for Wegener's granulomatosis: modification of
      the Birmingham Vasculitis Activity Score. International Network for the Study of
      the Systemic Vasculitides (INSSYS).
AB  - OBJECTIVE: To refine and validate the Birmingham Vasculitis Activity Score (BVAS)
      as a disease-specific activity index for Wegener's granulomatosis (WG). METHODS:
      Sixteen members of the International Network for the Study of the Systemic
      Vasculitides (INSSYS) revised the BVAS, with 3 goals: to reduce the redundancy of
      some component items, to enhance its ability to capture important disease
      manifestations specific to WG, and to streamline the instrument for use in
      clinical research. We defined the items and weighted them empirically as either
      minor (e.g., nasal crusting = 1 point) or major (e.g., alveolar hemorrhage = 3
      points). We then validated the new, disease-specific BVAS/WG in 2 simulation
      exercises and a clinical case series that involved 117 patients with WG. RESULTS:
      We removed 38 items from the original BVAS, revised 9 items, and added 7 new
      items. Correlations between the scores on the BVAS/WG and the physician's global
      assessment (PGA) of disease activity were high, even when patients in remission
      were excluded. In the clinical case series, Spearman's rank correlation
      coefficient between the BVAS/WG and the PGA was r = 0.81 (95% confidence interval
      0.73-0.87). The interobserver reliability using intraclass (within-case)
      correlation coefficients in the 2 simulation exercises was r = 0.93 for the
      BVAS/WG and r = 0.88 for the PGA in the first and r = 0.91 for the BVAS/WG and r
      = 0.88 for the PGA in the second. There was no significant observer effect in the
      scoring of the BVAS/WG or the PGA. The discriminant validity of the BVAS/WG was
      good: r = 0.73 (95% confidence interval 0.43-0.83). CONCLUSION: The BVAS/WG is a
      valid, disease-specific activity index for WG. Tested in simulation exercises and
      in actual patients, the BVAS/WG correlates well with the PGA, is sensitive to
      change, and has good inter- and intraobserver reliability. The INSSYS will use
      the BVAS/WG to assess the primary outcome in a phase II/III trial of etanercept
      in WG.

PMID- 11318007
TI  - Selective recall of gastrointestinal-sensation words: evidence for a cognitive
      behavioral contribution to irritable bowel syndrome.
AB  - OBJECTIVE: Selective attention to GI sensations has been suggested as an
      important mechanism that affects symptom perception in patients with irritable
      bowel syndrome (IBS), but this hypothesis has not yet been tested empirically.
      Differential recall of words describing negative affect has been used to
      demonstrate that depressed patients selectively attend to negative affect words.
      This technique may be useful for examining selective attention to somatic
      sensations. The aim of this study was to determine whether patients with IBS
      demonstrate selective recall of GI sensations compared with neutral words and
      words describing respiratory sensations. METHODS: A total of 16 IBS patients,
      nine asthmatic patients (medical controls), and eight healthy controls were shown
      10 GI sensation words or phrases, 10 respiratory sensation words or phrases, and
      10 neutral words in random order for 3 s each. After a distraction task, subjects
      wrote down all of the words or phrases they could remember. RESULTS: As
      predicted, IBS patients were more likely to recall GI words than other
      categories. Asthmatic patients were more likely to recall respiratory words in
      comparison with healthy controls. CONCLUSIONS: IBS patients selectively recall
      words describing GI sensations; this suggests that they may selectively attend to
      GI sensations, thus supporting the cognitive-behavioral theory of IBS.

PMID- 11318008
TI  - Association of HLA-DR genes with mild idiopathic adulthood biliary ductopenia.
AB  - OBJECTIVE: Mild idiopathic adulthood ductopenia (MIAD) is an asymptomatic chronic
      cholestatic liver disease characterized by the loss of interlobular bile ducts in
      <50% of the portal tracts. Although the underlying cause of MIAD is unknown, the
      host factors may contribute to the patient's susceptibility to the disease. The
      aim of this work was to investigate the immunogenetics in the pathogenesis of
      MIAD. METHODS: We prospectively studied 22 Caucasian patients with MIAD.
      Peripheral blood was collected, and HLA-DR typing was performed by polymerase
      chain reaction with sequence-specific primers followed by sequencing for
      subtyping. Results were compared with those from 140 age- and sex-matched
      controls. RESULTS: There was no significant association between HLA-DRB1 alleles
      and the disease, although a trend was found in MIAD patients with the DRB1*1502
      allele (five of 44 vs four of 280 in controls; p corrected = 0.055; chi2 = 13.9).
      Multiple HLA-DRB1 alleles (*04, *11, *15) showed increased frequencies in MIAD
      patients. Further subtyping revealed a motif (positions 25-32 of the beta1 chain)
      present in 17 (77.3%) patients, which was significantly associated with MIAD (p =
      0.049; chi2 = 3.87). Seven patients (31.8%) and 21 (15%) controls coded for this
      motif in their two alleles (p = 0.068; chi2 = 3.76). Among MIAD patients, those
      seven had abnormal ALT levels (p = 0.017) and their gamma-glutamyltransferase and
      ALT values tended to be more increased. CONCLUSIONS: These results provide
      evidence of an immunogenetic basis of susceptibility to MIAD in Caucasian
      individuals.

PMID- 11318009
TI  - Electrophysiological analysis of chronic atrial fibrillation associated with
      mitral valve disease by using spectral analysis.
AB  - Several authors have suggested that periodic activation is related to maintenance
      of atrial fibrillation (AF). The aim of this study was to examine periodic
      electrical activations in both atria that may lead to the generation and
      maintenance of AF associated with valvular diseases by means of fast Fourier
      transform (FFT) analysis. Atrial electrograms (AEGs) were analyzed in 15
      persistent AF patients, who underwent pulmonary vein orifice (PVO) isolation with
      mitral valve surgery. Intraoperatively, AEGs of 4 seconds duration were acquired
      at 48 epicardial sites, 24 each from the right and left atrium (RA, LA). Dominant
      peaks (DPs) examined using FFT were present in 26% of all sampling points
      (380/1440). Prominent clustering of DPs was mostly observed on the LA. The mean
      AF cycle length (mAFCL) estimated from DP frequency was significantly shorter in
      LA than that in RA (178 +/- 32 msec vs 247 +/- 58, p = 0.0003). The shortest AF
      cycle length in each patient was mainly found in the LA. The PVO isolation
      procedures successfully eliminated AF in 87% of patients (13/15). In cases of
      recurred AF (2/15), the difference in mAFCL between bilateral atria was
      significantly smaller than in the case of successful AF elimination (17 +/- 7
      msec vs 76 +/- 56, p = 0.042). FFT analysis of intraoperative mapping data
      clarified that periodic activity was present predominantly in LA. It may be
      possible to predict the efficacy of surgical procedures for eliminating AF using
      this technique.

PMID- 11318010
TI  - Myotonic dystrophy associated with VACTERL? A case report.

PMID- 11318011
TI  - Heat strain evaluation of chemical protective garments.
AB  - BACKGROUND: The purpose of this study was to compare thermoregulatory and
      subjective responses of 12 test subjects (10 male, 2 female) wearing 5 different
      Joint Service Lightweight Integrated Suit Technology (JSLIST) prototype and 3
      different currently fielded control chemical/ biological (CB) protective
      overgarments. METHODS: The overgarments were compared while subjects attempted to
      complete 100 min of moderate exercise (400 W) in an environmental chamber (35
      degrees C/50% rh). Rectal temperature (Tre), skin temperature, heart rate,
      sweating rate, and test time, as well as subjective symptoms of heat illness were
      measured. Data were analyzed for times earlier than 100 min because subjects were
      not usually able to complete the 100-min trials. RESULTS: At 50 min, of the 3
      controls, the Army/Air Force Battledress Overgarment (BDO) imposed significantly
      greater heat strain (indicated by Tre 37.90 degrees C) than the Marine Saratoga
      (SAR) (Tre 37.68 degrees C) and Navy Chemical Protective Overgarment (CPO) (Tre
      37.69 degrees C). The JSLIST prototype garments imposed heat strain (50 min Tre
      37.73-37.86 degrees C) as well as subjective perception of heat strain, that
      ranged between the warmest and coolest controls. CONCLUSIONS: In the
      environmental and exercise test conditions of this study, we did not find the
      five JSLIST overgarments to be consistently different from one another. Subjects
      in the control garments were and felt generally warmer (BDO) or cooler (SAR, CPO)
      than in the JSLIST prototype garments.

PMID- 11318012
TI  - Mobility, muscular strength and endurance in the cervical spine in Swedish Air
      Force pilots.
AB  - PURPOSE: Muscle strength, endurance and range of movement of the cervical spine
      in a group of Swedish Air Force jet pilots (AF) and in a reference group of
      conscripts doing their military service (RG) were compared. METHODS: We tested 30
      (AF) 24-42 yr and 33 (RG) 19-22 yr. A questionnaire was used to document
      complaints. Maximum voluntary isometric muscle strength of the flexor and
      extensor muscles of the cervical spine and sub-maximum isometric endurance in the
      flexor and extensor muscles were measured. RESULTS: Eleven AF (37%) and four RG
      (12%) had experienced discomfort in the neck within the previous year. The
      pilots' flexor and extensor muscle strength (47 Nm and 65 Nm) was superior to
      that of the conscripts (36 Nm and 59 Nm) (p = 0.0001, p = < 0.05, respectively).
      However, the RG group had greater isometric endurance in the flexor muscles than
      AF (p = < 0.05) and greater neck rotation (p = <0.005). There was no difference
      between the two groups in the other variables. CONCLUSION: Differences between
      the groups with regard to muscle strength and endurance might depend on
      variations in work-related physical muscle strain, and/or differences in fiber
      composition in the muscles, which might be reflected by pilot selection
      procedures.

PMID- 11318013
TI  - The performance of the standard rate turn (SRT) by student naval helicopter
      pilots.
AB  - BACKGROUND: During flight training, student naval helicopter pilots learn the use
      of flight instruments through a prescribed series of simulator training events.
      The training simulator is a 6-degrees-of-freedom, motion-based, high-fidelity
      instrument trainer. From the final basic instrument simulator flights of student
      pilots, we selected for evaluation and analysis their performance of the Standard
      Rate Turn (SRT), a routine flight maneuver. METHODS: The performance of the SRT
      was scored with air speed, altitude and heading average error from target values
      and standard deviations. These average errors and standard deviations were used
      in a Multiple Analysis of Variance (MANOVA) to evaluate the effects of three
      independent variables: 1) direction of turn (left vs. right), 2) degree of turn
      (180 vs. 360 degrees); and 3) segment of turn (roll-in, first 30 s, last 30 s,
      and roll-out of turn). RESULTS: Only the main effects of the three independent
      variables were significant; there were no significant interactions. This result
      greatly reduces the number of different conditions that should be scored
      separately for the evaluation of SRT performance. The results also showed that
      the magnitude of the heading and altitude errors at the beginning of the SRT
      correlated with the magnitude of the heading and altitude errors throughout the
      turn. This result suggests that for the turn to be well executed, it is important
      for it to begin with little error in these two response parameters. CONCLUSIONS:
      The observations reported here should be considered when establishing SRT
      performance norms and comparing student scores. Furthermore, it seems easier for
      pilots to maintain good performance than to correct poor performance.

PMID- 11318014
TI  - Survey of Israeli Air Force line commander support for fatigue prevention
      initiatives.
AB  - BACKGROUND: Sustained and continuous high intensity military operations have
      increased in scope in recent years. These mandate ever more sophisticated efforts
      to prevent and ameliorate aviator fatigue. Successful implementation of new
      fatigue countermeasures requires thorough pretesting among experienced aviator
      opinion leaders: base and squadron commanders. METHODS: An anonymous and
      voluntary survey questionnaire containing background material and Likert-scale
      questions regarding 14 primary through tertiary fatigue prevention initiatives
      current in the aeromedical literature or unique to the IAF was distributed to all
      base and flight squadron commanders in the IAF. RESULTS: Of the commanders, 38%
      returned fully completed questionnaires. The most popular primary prevention
      initiatives (garnering 87% support) dealt with reservist aviators: 1.) requiring
      reserve pilots to arrive at the squadron at least 3 h before night flights to
      facilitate napping time, and 2.) improving scheduling coordination of those
      reservists employed as civilian aircrew. The chief (88% support) secondary
      prevention countermeasure endorsed was to utilize stimulant drugs such as
      caffeine or amphetamines to sustain the alertness of fatigued aviators. Leading
      the list of tertiary prevention initiatives (75% support) was the suggestion that
      squadrons debrief the incidence of aviator fatigue, as well as their success in
      the area of time-management when debriefing high tempo exercises and operational
      missions. CONCLUSIONS: Commanders differentially supported a wide range of
      fatigue countermeasures. Use of stimulant drugs achieved the broadest support.
      Instituting specific measures to facilitate alertness in reservist aviators was
      also a priority. Surveying the degree of commander support for new fatigue
      prevention initiatives provides the basis for prioritization of scarce resources,
      should improve line cooperation, and provides important experience-proven
      feedback for researchers and policy-makers.

PMID- 11318015
TI  - Bosnia and Kosovo: aeromedical evacuation in the initial stages of deployment.
AB  - METHOD: A comparative analysis of aeromedical evacuation (AE) from operations in
      Bosnia-Herzegovina and Kosovo during the first months of deployment was performed
      in order to determine how medical assets were utilized and to explore the
      potential for multi-national cooperation. METHODS: Retrospective analysis of
      casualties evacuated and aircraft utilization during the first 4 mo of both
      operations and the first year of deployment to Operation Joint Endeavor (Bosnia
      Herzegovina) was performed. RESULTS: Categories of casualties evacuated (in
      accordance with international ICD codes) were compiled, and most frequent
      diagnoses of patients evacuated, average patient load, and frequency of critical
      care team transport were determined. CONCLUSIONS: To increase cooperation among
      multi-national forces deployed to the same operation, a database can be
      established with numbers and diagnoses of casualties evacuated. Trended data can
      then be used to tailor AE forces to meet both medical needs and multi-national
      operation requirements.

PMID- 11318016
TI  - Parasympathetic activity during parabolic flight, effect of LBNP during
      microgravity.
AB  - BACKGROUND/HYPOTHESIS: During parabolic flight, in the standing position, changes
      are partly due to an acute shift in fluid between the lower extremities, the head
      and the thorax (Vaida P, et al. J Appl Physiol 1997; 82:1091-7; and Bailliart O,
      et al. J Appl Physiol 1998; 85:2100-5). We hypothesized that modifications of
      parasympathetic activity associated with changes in hydrostatic pressure
      gradients induced by changes in gravity could be detected by analysis of short
      time periods. METHODS: We assessed heart rate variability (HRV) in 11 healthy
      volunteers by indices of temporal analysis (NN, SDNN, RMSSD) and normalized
      indices such as coefficients of variation CV-SDNN and CV-RMSSD and ratio
      SDNN/RMSSD. A lower body negative pressure (LBNP) at -50 mm Hg was randomly
      applied during the microgravity phase (0 Gz) to counteract the lack of
      hydrostatic pressure in the lower part of the body. RESULTS: NN, CV-SDNN and CV
      RMSSD decreased during hypergravity phases and increased during microgravity and
      during early normogravity (1 Gz) period at the end of parabolas. With LBNP
      changes are less pronounced at 0 Gz and in the 1 Gz post parabolic period.
      CONCLUSION: We concluded that parasympathetic nervous activity is recordable by
      temporal analysis of HRV during short periods of time. LBNP applied during 0 Gz
      phase reduced the parasympathetic activation at 0 Gz and post parabolic 1 Gz.

PMID- 11318017
TI  - Urine volume and its effects on renal stone risk in astronauts.
AB  - BACKGROUND: Urine composition in astronauts during and immediately after
      spaceflight changes in ways that increase the renal stone-forming potential for
      calcium oxalate, calcium phosphate, and uric acid saturation. We examined the
      effect of urine volume on the risk of renal stone formation in 356 astronauts.
      METHODS: Renal stone-forming risk was evaluated from 24-h urine samples collected
      from astronauts before and after 4- to 17-d Space Shuttle flights. Urinary
      chemistries were performed and the relative supersaturations of calcium oxalate,
      brushite, sodium urate, struvite, and uric acid saturation were calculated from
      the biochemical results. RESULTS: Urinary supersaturation levels of stone-forming
      salts were inversely related to urinary output both before and after spaceflight.
      Urine volume > 2 L x d(-1) reduced the risk of renal-stone development without
      affecting urinary citrate concentrations as compared with the increased risk
      observed in those astronauts who excreted urine volumes < L x d(-1). CONCLUSION:
      Results from this study indicate that increasing daily urinary output alone is an
      effective countermeasure to reduce the renal stone-forming risk immediately after
      spaceflight. However, increasing urinary output during flight may not be entirely
      effective in minimizing the potential risk of renal stone formation due to the
      changes in the urine chemistry in astronauts exposed to microgravity. KEYWORDS:
      urine volume, spaceflight, renal calculi.

PMID- 11318018
TI  - Cardiovascular effects of verapamil and quinidine at normal and elevated ambient
      pressure.
AB  - Cardiovascular parameters were measured in rats before and after administration
      of verapamil and quinidine, a slow Ca2+ and fast Na+ channel blocker,
      respectively, at normal and elevated ambient pressure [5 bar (500 kPa)]. Left
      ventricular pressure (Pivt), maximal velocity of Plvt rise (+dP/dt) and fall (
      dP/dt), and heart rate (HR), arterial systolic pressure (Pasys), and mean
      arterial pressure (MAP) were measured in all animals using catheters connected to
      pressure transducers. Cardiac output (Q), and myocardial blood flow (MBF) were
      detected by the microsphere technique. Total peripheral vascular resistance
      (TPVR), myocardial vascular resistance (MVR) and oxygen consumption of the heart
      (VO2) was calculated. In Groups 1a (control group; 1 bar) and 1b (test group; 1-5
      bar), verapamil (1.5 mg x kg(-1)) caused a reduction in Plvt, +dP/dt, -dP/dt,
      Pasys, MAP, VO2, TPVR, and MVR in both groups at 1 bar (100 kPa), and these
      parameters remained depressed for at least 50 min in Group 1a. However, MBF
      increased after verapamil injection. After compression to 5 bar (500 kPa), Plvt,
      dP/dt, Pasys, VO2, and MBF were markedly elevated (Group 1b). No change in HR,
      SV, or Q was found in either of the groups. In Groups 2a (control group; 1 bar)
      and 2b (test group; 1-5 bar), quinidine (5 mg x kg(-1)), infused over a period of
      10 min, reduced Plvt, +dP/dt, -dP/dt, MAP, Pasys, VO2, Q, stroke volume (SV),
      TPVR and MBF at 1 bar (100 kPa). These parameters remained depressed for almost
      the whole experimental period in Group 2a, while Plvt, +/-dP/dt, Pasys, MAP and
      VO2 were enhanced during exposure to 5 bar (500 kPa) in Group 2b. The HR was
      unchanged by quinidine in Group 2a, but was increased at elevated ambient
      pressure in Group 2b, whereas the MBF was unchanged in both groups. The present
      results show that verapamil and quinidine have a depressant effect on cardiac
      function, arterial pressure and VO2 at normal atmospheric pressure, whereas MBF
      was enhanced only in the verapamil group. During exposure to elevated ambient
      pressure, cardiac function, arterial pressure and VO2 increased despite adequate
      inhibition of slow Ca2+ and fast Na+ channels.

PMID- 11318019
TI  - Decrease in platelet count during saturation diving.
AB  - BACKGROUND: The change in platelet count (PC) occurring during saturation diving
      has rarely been discussed. We set out to clarify the details of this change in
      PC, and its relationship with: i) the storage depth and duration of the
      saturation dive, and ii) the presence of decompression bubbles. METHODS: In a
      total of 42 divers, the change in PC was measured in 8 simulated saturation dives
      (1992-1998) using a Deep Diving Simulator with decompression procedures based on
      the modified DUKE-GKSS schedule. Blood samples were taken before the dive, at the
      bottom (twice), during decompression, on surfacing, and about 1 wk after
      surfacing. Decompression bubbles were examined by ultrasonic M-mode
      echocardiography. RESULTS: PC (mean +/- SD x 10(4) x microl(-1)) was 23.9 +/-
      4.85, 24.9 +/- 4.9, 24.2 +/- 4.8, 19.2 +/- 4.4*, 20.1 +/- 4.5*, 25.0 +/- 5.1 on
      the occasions listed above (*= p < 0.05 vs. pre-dive). The PC showed no
      correlation with either storage depth or dive duration. Decompression bubbles
      were detected during decompression in only 2 divers (4.8%), and the bubbles
      disappeared immediately after surfacing. In these 2 divers the decreases in PC
      values from baseline to the middle of decompression and on surfacing were 2 and
      2.7 x 10(4) x microl(-1), and 3.4 and 1.7 x 10(4) x microl(-1) respectively. No
      diver complained of decompression sickness. CONCLUSION: The magnitude of the
      decrease in PC (< 5 x 10(4) x microl(-1)) and the time to recover to the pre-dive
      value (< 1 wk) suggests that changes in PC during saturation diving should not
      cause any clinical problems. The mechanisms underlying the decrease in PC remain
      unclear.

PMID- 11318020
TI  - Effect of daily versus intermittent exposure on heat acclimation.
AB  - In order to compare the effectiveness of a daily to an intermittent acclimation
      protocol, 14 competitive rowers (mean +/- SD VO2peak = 48 +/- 7 ml x kg x min(
      1)) were randomly assigned to either a consecutive (10 consecutive days) or
      intermittent acclimation group (10 sessions over 3 weeks). For every heat
      exposure, subjects in each group exercised for 30 min at 70% VO2peak in an
      environmental chamber set at 38 degrees C and 70% relative humidity. Acclimation
      state was monitored by measuring heart rate (HR), rectal and skin temperature
      (Tre and Tsk), ratings of perceived exertion (RPE) and whole body sweat rate (SR)
      during each heat exposure. Final exercise Tre decreased significantly by 0.6 +/-
      0.7 degrees C with intermittent heat exposure but the decrease was significantly
      larger (p < 0.05) with consecutive day heat exposure (1.0 +/- 0.1 degrees C).
      Final exercise HR also decreased significantly by 13 +/- 12 bpm (p < 0.05) in the
      consecutive group, and non-significantly by 5 +/- 13 bpm in the intermittent
      group. RPE decreased with daily (5 +/- 1, p < 0.05) but did not significantly
      decrease with intermittent heat exposure (1 +/- 3). Similarly, Tsk significantly
      decreased with consecutive (0.4 +/- 0.2 degrees C, p < 0.05) but not intermittent
      exposure (0.2 +/- 0.3 degrees C) and SR did not change in either group. Minimal
      adaptation occurs with intermittent heat exposure and it appears that daily heat
      exposure is the most effective acclimation strategy.

PMID- 11318021
TI  - Personality factors, stoicism and motivation in subjects under hypoxic stress in
      extreme environments.
AB  - Previous studies on the physiological and psychological adaptation of subjects to
      survival conditions involving high-altitude hypoxia (>6,500 m) have shown that
      personality factors are important in this adaptation. We, therefore, proposed
      personality traits assessments in two groups of subjects engaged in sporting
      activities under extreme hypoxic environmental conditions: a group of
      mountaineers at high altitudes (>5,500 m) and a group of free-lung divers at
      great depths (<30-60 m). These subjects were compared with two control groups: a
      group of subjects practicing no sport and another one practicing various
      competitive athletic activities involving speed constraints. The personality
      traits assessed concerned mainly the subjects' attitudes and their propensities
      to act out their feelings and fantasies; they were assessed using projective
      procedures, the Hand Test and Clark's Situational Pain Questionnaire based on the
      Sensory Decision Theory. Subjects trained in mountaineering and free-lung diving
      under extreme environmental conditions displayed a high degree of stoicism. These
      individuals shared some personality traits with other sportsmen, particularly
      aggressive tendencies and introversion although not to an extent which interfered
      with normal interpersonal relationships. However, at least when practicing these
      extreme sports, the subjects did retreat from society. One of our questions
      concerns the grounds for this social withdrawal, that is, whether it derives from
      a inner compulsion founded on personality factors or if it is merely an artifact
      of our perceptions of the subjects, created by the confluence of the
      individualistic nature of these sports and the extreme environments in which they
      are performed.

PMID- 11318022
TI  - Double hearing protection and speech intelligibility-room for improvement.
AB  - INTRODUCTION: Double hearing protection is used in many air forces around the
      world for protection in noisy aircraft environments, particularly in helicopters.
      The usual combination is foam ear plugs under headset or helmet muffs. Much of
      the research that spurred the introduction of foam earplugs indicated little
      change in speech intelligibility in persons with normal hearing. However, aircrew
      often complain about having to maximize intercom volume for speech understanding,
      causing a situation with no reserve volume and bad sound quality. In recent
      years, further developments have included so-called hi-fi plugs and custom made
      ear plugs which are claimed to improve speech communication. The aim of the
      present project was to investigate different types of ear plugs and their effect
      on speech intelligibility in helicopter noise. METHODS: Each of nine normal
      hearing pilot subjects were placed in an environment of recorded helicopter noise
      from a BO-105 helicopter. Speech audiometry was performed under four different
      conditions: headset only, and three different ear plugs worn under the headset.
      Fitting of the ear plugs was performed by an ear, nose and throat specialist to
      ensure similar conditions. The sequence of test conditions was randomized and
      double-blind. In addition, a subjective rating scale was used. RESULTS: Wearing
      foam ear plugs under the headset decreased speech intelligibility dramatically.
      The "hi-fi" plug was somewhat better than foam plugs, and the custom made ear
      plug provided a speech intelligibility close to the headset-only situation.
      Subjective rating scores coincided with these findings. DISCUSSION: In helicopter
      noise, custom made ear plugs may provide a much improved speech intelligibility
      over conventional plugs when worn under a headset, while maintaining improved
      noise protection over the headset-alone situation. Custom made ear plugs might
      therefore be a good alternative to other forms of enhanced noise protection in
      helicopters.

PMID- 11318023
TI  - Out of Africa.

PMID- 11318024
TI  - CRM and the practice of medicine.

PMID- 11318026
TI  - Let's go to Mars!

PMID- 11318025
TI  - Voice stress monitoring in space.

PMID- 11318027
TI  - Anxiety and depressive states in multiple chemical sensitivity.
AB  - Cases with multiple chemical sensitivity (MCS) frequently present mental
      symptoms. This study discusses the characteristics of the anxiety and depressive
      state of MCS by comparing patients of MCS with a gender and age-matched control
      group. In this investigation, MCS cases were selected among those satisfying the
      diagnostic criteria of Cullen after ruling out other physical diseases. Patients
      visiting ophthalmologists with other diseases were designated as the control.
      Evaluation of the anxiety and depressive state was performed in 48 cases of MCS
      and 48 controls using the Japanese version of the State-Trait Anxiety Inventory,
      the Self-rating Depression Scale (SDS), and the Hamilton Rating Scale for
      Depression. Significantly higher mean values of subjective anxiety and a
      depressive state were obtained in 18 MCS cases than in 18 controls for the follow
      up patients, while no significant difference was observed between MCS and
      controls of 30 new patients for each group. Therefore, anxiety in MCS is
      characterized by the continuous high anxiety level. MCS is also characterized by
      a continuance of depressive state at a "neurotic level" category by SDS. The
      anxiety scores and depressive levels were highly correlated in MCS and controls
      at the first and subsequent appearances, except those in the follow-up control
      cases. In conclusion, both anxiety and a depressive state in MCS remained at high
      level until the subsequent examination, when those in controls decreased to a
      normal level.

PMID- 11318028
TI  - Monitoring of minimal residual disease in children with acute promyelocytic
      leukemia by RT-PCR detecting PML/RARalpha chimeric gene: a retrospective study of
      clinical feasibility.
AB  - We studied retrospectively the clinical feasibility of minimal residual disease
      (MRD) monitoring by reverse transcription-polymerase chain reaction (RT-PCR)
      detecting the PML/retinoic acid receptor alpha (RARalpha) chimeric gene in
      children with acute promyelocytic leukemia (APL). MRD monitoring of APL was
      performed with standard and nested RT-PCR for PML/RARalpha gene, the sensitivity
      of which was 1 leukemic cell in 10(3)-10(4) and 1 in 10(4)-10(5) cells,
      respectively. Patients were nine children with APL (average age: 8.3 year;
      average period of follow-up: 69.2 months) who, after achieving remission with all
      trans retinoic acid (ATRA), received treatment either with multidrug chemotherapy
      or with a combination of chemotherapy and ATRA. Out of six patients treated with
      multidrug-combined chemotherapy, two patients exhibited PCR positivity after six
      months of post- remission therapy, which shifted from the detectable range of the
      nested PCR to that of the standard PCR. These two patients subsequently relapsed
      and, together with two of the other patients receiving multidrug-combined
      chemotherapy, underwent allogeneic bone marrow transplantation. No MRD was
      detected in these patients after transplantation. In the remaining three patients
      who underwent cyclic treatment with alternative chemotherapy and ATRA, two showed
      positive RT-PCR at the nested or standard level, respectively, after six months
      of combined therapy, and one of them relapsed. Overall, three of four patients
      with MRD detected in post-remission period ultimately relapsed, while all of five
      patients without detectable MRD had a good prognosis. These findings suggest that
      impending relapse may be predicted by the detection of preceding PCR positivity
      with an increasing quantity of the PML/RARalpha mRNA that appears beyond six
      months of post-remission chemotherapy, with or without combined ATRA therapy.

PMID- 11318029
TI  - Participatory assessment of the environment from children's viewpoints:
      development of a method and its trial.
AB  - To understand the actual viewpoints of children about daily life and the
      environment, the authors, adopting a participatory strategy, visited 21 classes
      of Japanese school children, improved in a stepwise process their ways of
      question-asking, and developed "WIFY"(what is important for you); a set of
      interactive questions composed of a basic question and three accompanying
      instructions. In applying WIFY, 59 fourth graders, 22 in Nagasaki, Japan and 37
      in Beijing, China, reported their viewpoints in each of classroom settings. In
      both settings, when children were allowed to communicate with each other by the
      use of WIFY answering sheet, spontaneous exchanges arose and continued. WIFY
      itself is supposed to bring out and enhance mutual collaboration and spontaneous
      networking. In this instance, WIFY functioned as a communication tool. When
      answering sheets were collected and obtained responses were analyzed as cases, a
      rather materialistic view was suggested among Japanese children and a more
      disciplined view, which put much value on school and home, was suggested among
      Chinese children. Further studies are needed to confirm the changing
      environmental views of children from the collaborative research framework.

PMID- 11318030
TI  - Clinical significance of circulating cancer cells in peripheral blood detected by
      reverse transcriptase-polymerase chain reaction in patients with breast cancer.
AB  - Detection of breast cancer micrometastases based on specific genetic markers may
      provide useful information to justify appropriate therapeutic strategies. We
      examined the presence of a carcinoembryonic antigen (CEA) messenger RNA(mRNA) in
      the peripheral blood of 32 patients with varying stages of breast cancers by
      means of the reverse transcriptase-polymerase chain reaction (RT-PCR) assay prior
      to and after the curative operation. CEA mRNA were detected in the peripheral
      blood samples from 12 (38%) out of 32 breast cancer patients prior to surgery.
      Among 12 CEA mRNA-positive patients prior to surgery, 4 (33.3%) relapsed from
      breast cancer within 2 years after surgery. Moreover, CEA mRNA was detected in
      the peripheral blood samples obtained prior to surgery in 3 out of 11 patients
      (27.2%) with a stage I disease. One out of three of these patients had a relapse
      in lung. There were four patterns of CEA mRNA expression, ( +, + ), (+, -), (-, +
      ), and (-, -) in the pre- and post-operative blood samples. In 12 CEA mRNA
      positive patients submitted to surgical resection of the primary tumor,
      persistence of CEA mRNA expression was observed in five patients (+, +) within a
      month after surgical treatment. Three out of these 5 patients (60%) relapsed from
      breast cancer within 2 years after surgery. In 7 other patients (+, -), CEA mRNA
      expression was not detected within a month after tumor removal, and recurrence
      occurred in 1 out of the 7 patients (14%) within 2 years after surgery. In 19
      patients, CEA mRNA expression was not detected in pre- or post-operative blood
      samples (-, -). There was a patient whose blood sample was negative for CEA mRNA
      before the operation, but changed to show a positive result after surgery (-,+).
      No recurrence was found in 20 of CEA mRNA-negative patients prior to surgery (-,
      +), (-, -). This study suggested that the presence of CEA mRNA expression in
      preoperative peripheral blood sample represent the progression of the disease,
      especially the risk of hematogenous metastasis in the patients in spite of their
      clinical stage, and the presence of CEA mRNA in the postoperative blood sample
      may represent the evidence of a residual disease. Thus consideration might be
      given for adding combined multi-modal therapy.

PMID- 11318031
TI  - Adrenomedullin from a pheochromocytoma to the eye: implications of the
      adrenomedullin research for endocrinology in the 21st century.
AB  - In the last several decades, the concept of "endocrinology" has been greatly
      changed. One major change was due to the discovery of peptide hormones secreted
      by the organs that were not "classical" endocrine organs. For example,
      corticotropin-releasing hormone and many neuropeptides are secreted by the
      neurons, atrial natriuretic peptide by the heart, endothelin-1 by the vascular
      endothelial cells, and leptin by the adipose tissues. Now, the brain, heart,
      vascular tissue and adipose tissue can be considered to be endocrine organs.
      Cardiovascular diseases and obesity are therefore important targets of the
      endocrine research. Adrenomedullin is a potent vasodilator peptide consisting of
      52 amino acids. It was originally discovered from a human pheochromocytoma, and
      belongs to the calcitonin gene-related peptide (CGRP) family. Adrenomedullin is
      produced and secreted by various types of cells, for example, vascular
      endothelial and smooth muscle cells, cardiomyocytes, fibroblasts, macrophages,
      neurons, glial cells, and retinal pigment epithelial cells. Such ubiquitous
      expression has not been observed in other neuropeptides, including neuropeptide Y
      and CGRP. Expression of adrenomedullin is induced by hypoxia and proinflammatory
      cytokines. In addition to vasodilator actions, this peptide has central
      inhibitory actions on water drinking and salt appetite, effects on the secretion
      of some hormones and cytokines, inotropic actions and effects on cell growth and
      apoptosis. Adrenomedullin is produced by various non-endocrine tumors, as well as
      endocrine tumors, and acts as a growth stimulatory factor for the tumor cells.
      Adrenomedullin seems to be involved in the pathophysiology of many diseases,
      including ischemic heart diseases, inflammatory diseases, tumors, and even eye
      diseases. The adrenomedullin research implies that "the neuroendocrine system"
      exists in much broader types of cells than previously thought, and that the
      endocrine research is able to contribute to the understanding of the
      pathophysiology of many diseases.

PMID- 11318032
TI  - Aromatic hydroxylation catalyzed by toluene 4-monooxygenase in organic
      solvent/aqueous buffer mixtures.
AB  - Toluene 4-monooxygenase is a four-protein component diiron enzyme complex. The
      enzyme catalyzes the hydroxylation of toluene to give p-cresol with approximately
      96% regioselectivity. The performance of the enzyme in two-phase reaction systems
      consisting of toluene, hexane, or perfluorohexane and an aqueous buffer was
      tested. In each of the cosolvent systems, containing up to 93% (v/v) of solvent,
      the enzyme was active and exhibited regioselectivity indistinguishable from the
      aqueous reaction. Using the perfluorohexane/buffer system, a number of polycyclic
      aromatic hydrocarbons were oxidized that were not readily oxidized in aqueous
      buffer. An instability of the hydroxylase component and a substantial uncoupling
      of NADH utilization and product formation were observed in reactions that were
      continued for longer than approximately 3 min. More stable enzyme complexes will
      be needed for broad applicability of this hydroxylating system in nonaqueous
      media.

PMID- 11318033
TI  - Lichenysin: a more efficient cation chelator than surfactin.
AB  - The lipopeptide lichenysin (cyclo-[L-Gln1-->D-Leu2-->L-Leu3-->L-Val4--> L-Asp5-
      >D-Leu6-->L-Ile7-beta-OH fatty acid]) produced by Bacillus licheniformis
      structurally resembles surfactin from Bacillus subtilis. The main difference is
      the presence of a glutaminyl residue in position 1 of the peptide sequence in
      place of glutamic acid in surfactin. This local variation causes significant
      changes in the properties of the molecule compared to surfactin. Lichenysin has a
      higher surfactant power, the critical micellar concentration (c.m.c.) being
      strongly reduced from 220 to 22 microM and a much higher hemolytic activity
      because 100% hemolysis was observed with only 15 microM instead of 200 microM.
      Lichenysin is also a better chelating agent because its association constants
      with Ca2+ and Mg2+ are increased by a factor of 4 and 16, respectively. This
      effect is assigned to an increase in the accessibility of the carboxyl group to
      cations owing to a change in the side chain topology induced by the Glu/Gln
      exchange. Additionally, the propensity of the lipopeptide for extensive
      hydrophobic interactions, as illustrated by its low c.m.c., contributes to
      further stabilization of the cation and an increase in the partitioning of
      lichenysin into the erythrocyte membrane. Our data support the formation of a
      lichensyin-Ca2+ complex in a molar ratio of 2:1 instead of 1:1 with surfactin,
      suggesting an intermolecular salt bridge between two lichenysin molecules.
      Therefore, when Ca2+ ions are present in the solution, micellization occurs via a
      dimer assembly, with a possible long-range effect on the spatial arrangement of
      the micelles or other supramolecular structures. Finally, among all the surfactin
      peptidic variants so far known, lichenysin is the one for which the three tested
      activities are the most substantially improved.

PMID- 11318034
TI  - Purification of alpha-amylases using magnetic alginate beads.
AB  - Magnetic alginate beads were used to purify alpha-amylases from porcine pancreas,
      starchzyme, BAN 240L (a commercial purification from Bacillus subtilis), and
      wheat germ. The beads bound a significant level of alpha-amylase activity from
      porcine pancreas, BAN 240L, and wheat germ. In each case, the enzyme activity
      could be eluted by using 1.0 M maltose, a known competitive inhibitor of alpha
      amylase. In the case of BAN 240L, 3.6-fold purification with 72% recovery of
      activity was observed. In the case of wheat germ enzyme, starting from the crude
      extract, 48-fold purification with 70% activity recovery was observed. Sodium
      dodecyl sulfate polyacrylamide gel electrophoresis analysis also indicated
      considerable purification in the latter case.

PMID- 11318035
TI  - Conversion of ammonia to dinitrogen in wastewater by Nitrosomonas europaea.
AB  - Because Nitrosomonas europaea contains ammonia-oxidizing enzyme, nitrite
      reductase, and nitrous oxide reductase, the conversion of ammonia to dinitrogen
      was tried with different reaction conditions. In aerobic reaction conditions,
      ammonium was converted to nitrite (NO2-), while under oxygen-limiting or oxygen
      free conditions, NO2(-)-N formed from ammonia oxidation by N. europaea was
      reduced to N2O and dinitrogen with 22% conversion. During denitrification,
      optimal pH for the production of N2O and dinitrogen was found to be 7.0-8.0.
      Dinitrogen was not produced in acidic pH <7.0. A low partial oxygen pressure as
      well as oxygen-free conditions are favorable for high production of dinitrogen.

PMID- 11318036
TI  - Cooperativity and substrate specificity of an alkaline amylase and neopullulanase
      complex of Micrococcus halobius OR-1.
AB  - The saccharifying alkaline amylase and neopullulanase complex of Micrococcus
      halobius OR-1 hydrolyzes both alpha-(1,4)- and alpha-(1,6)-glycosidic linkages of
      different linear and branched polysaccharides. The following observations were
      made concerning the analysis of the coexpressed amylase and neopullulanase
      enzymes. Even though the enzymes were subjected to a rigorous purification
      protocol, the activities could not be separated, because both the enzymes were
      found to migrate in a single peak. By contrast, two independent bands of
      amylolytic activity at 70 kDa and pullulanolytic activity at 53 kDa were evident
      by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), reducing
      and nonreducing PAGE, and zymographic analysis on different polysaccharides.
      Preferential chemical modification of the enzyme and concomitant high-performance
      thin-layer chromatographic analyses of the saccharides liberated showed that
      amylase is sensitive to 1-(dimethylamino-propyl)-3-ethyl carbodiimide-HCl and
      cleaved alpha-(1,4) linkages of starch, amylose, and amylopectin producing
      predominantly maltotriose. On the other hand, formalin-sensitive neopullulanase
      acts on both alpha-(1,4) and alpha-(1,6) linkages of pullulan and starch with
      maltotriose and panose as major products. It is understood that neopullulanase
      exhibits dual activity and acts in synergy with amylase toward the hydrolysis of
      alpha-(1,4) linkages, thereby increasing the overall reaction rate; however, such
      a synergism is not seen in zymograms, in which the enzymes are physically
      separated during electrophoresis. It is presumed that SDS-protein intercalation
      dissociated the enzyme complex, without altering the individual active site
      architecture, with only the synergism lost. The optimum temperature and pH of
      amylase and neopullulanase were 60 degreesC and 8.0, respectively. The enzymes
      were found stable in high alkaline pH for 24 h. Therefore, the saccharifying
      alkaline amylase and neopullulanase of M. halobius OR-1 evolved from tapioca
      cultivar shows a highly active and unique enzyme complex with several valuable
      biochemical features.

PMID- 11318038
TI  - Phosphodiesterase production in an aqueous two-phase system by Nicotiana tabacum
      1507.
AB  - Studies were conducted on the production of phosphodiesterases by Nicotiana
      tabacum 1507 cell suspension in an aqueous two-phase system formed by adding 4%
      polyethylene glycol (mol wt 20,000) and 7.5% dextran (mol wt 70,000) to the
      medium. The time course of growth, biosynthesis, secretion, and partitioning of
      phosphodiesterases was followed in comparison with N. tabacum 1507 cultivation as
      a free suspension. Partitioning of phosphodiesterases took place mainly in the
      bottom dextran phase, and a possibility was revealed for obtaining an enzyme
      preparation with high phosphodiesterase activity.

PMID- 11318039
TI  - Self-efficacy perceptions in oral health behavior.
AB  - The aim of this paper is to describe and understand people's views on dental self
      efficacy and its formation. The qualitative data were collected by means of
      focused interviews with five patients selected on the basis of poor orientation
      to dental-care matters, measured using test scores from a previous questionnaire.
      The first stage of the analysis is a description of the background of the
      subjects from their own accounts; two proved to have internalized preventive
      dental beliefs and behavior deeply while two others had traumatic experiences as
      a reason for irregular dental appointments. One subject with poor oral health
      behavior seemed to have limited preventive action to his yearly dental
      appointment. The second stage of the analysis focuses on interpretation of the
      subjects' perception of self-efficacy and related comments. Among sources of self
      efficacy that prove important in dental care are the cognitive, experiential,
      supportive and emotional dimensions, and beliefs and values learned in the family
      and at school. This qualitative research increases our understanding of the oral
      health behavior of patients and emphasizes the importance of patient-centered
      oral health education.

PMID- 11318037
TI  - Pretreatment with ammonia water for enzymatic hydrolysis of corn husk, bagasse,
      and switchgrass.
AB  - Bagasse, corn husk, and switchgrass were pretreated with ammonia water to enhance
      enzymatic hydrolysis. The sample (2 g) was mixed with 1-6 mL ammonia water (25
      28% ammonia) and autoclaved at 120 degreesC for 20 min. After treatment, the
      product was vacuum-dried to remove ammonia gas. The dried solid could be used
      immediately in the enzymatic hydrolysis without washing. The enzymatic hydrolysis
      was effectively improved with more than 0.5 and 1 mL ammonia water/g for corn
      husk and bagasse, respectively. In bagasse, glucose, xylose, and xylobiose were
      the main products. The adsorption of CMCase and xylanase was related to the
      initial rate of enzymatic hydrolysis. In corn husks, arabinoxylan extracted by
      pretreatment was substantially unhydrolyzed because of the high ratio of
      arabinose to xylose (0.6). The carbohydrate yields from cellulose and
      hemicellulose were 72.9% and 82.4% in bagasse, and 86.2% and 91.9% in corn husk,
      respectively. The ammonia/water pretreatment also benefited from switchgrass
      (Miscanthus sinensis and Solidago altissima L.) hydrolysis.

PMID- 11318040
TI  - Usefulness of a psychometric questionnaire in exploring parental attitudes in
      children's dental care.
AB  - In this methodological study we investigated the usefulness and reliability of a
      questionnaire designed to capture 4 aspects of parental dental attitudes: dental
      knowledge, child oral health behavior, perceived importance of dental related
      aims, and parental responsibility. The study was undertaken in a group of 140
      parents of schoolchildren aged 8-12 years from four comprehensive schools in
      Sweden. Test-retest reliability, quantified by the intraclass correlation
      coefficient (ICC) or by Cohen's kappa, varied from acceptable to excellent for
      different aspects of the questionnaire. The knowledge and responsibility-taking
      sections were also answered by a group of dental experts who showed a high level
      of internal agreement. Expert profiles, to which the parental assessments could
      be compared, were created. Exploration of the 4 aspects showed that this group of
      parents commonly had a multifocal view on the etiology and prevention of caries.
      Correlations between their knowledge assessments and the assessments made by the
      expert group varied from moderately negative to strongly positive. The parents
      revealed a high degree of dental-related motivation and responsibility,
      particularly according to oral health behaviors. In conclusion, the results
      indicate that this 4-part psychometric questionnaire might be a suitable
      instrument in investigations of priority and responsibility-taking as new aspects
      of parental dental attitudes, along with dental knowledge and child oral health
      behaviors.

PMID- 11318041
TI  - Restorative treatment decisions on occlusal caries in Scandinavia.
AB  - In order to map variations in the operative treatment threshold for occlusal
      caries, a pre-coded questionnaire was sent to a random sample of 759 dentists in
      Norway, 923 in Sweden, and 173 in the Danish Public Dental Health Service
      inquiring about caries and treatment strategies. A further intention was to
      explore the type of operative treatment and filling material dentists in
      Scandinavia would use given an occlusal lesion in the lower 2nd molar in a 20
      year-old. It is found that close to 70% of dentists in the 3 countries would put
      off carrying out operative treatment of occlusal caries until they registered a
      moderately sized cavity and/or any radiolucency in dentin. In Sweden, 26.7% of
      dentists and in Denmark 24.3% would postpone operative treatment until the lesion
      had a large cavity and/or until radiolucency could be observed in the middle
      third of the dentin; in Norway, only 11.5% of dentists indicated this. The
      majority of dentists in all 3 countries preferred to drill only the carious part
      of the fissure, though in Norway more dentists (30.9%) would tend to drill the
      whole fissure compared to their Swedish (23.4%) and Danish (9.5%) colleagues. The
      majority of Danish dentists (52.4%) suggested amalgam for restoring the occlusal
      surface, while 19.9% of Norwegian and 2.9% of Swedish dentists would use amalgam.
      Composite was the first material of choice for 71.5% of the Swedish dentists, the
      remaining 25.6% suggesting conventional glass ionomer cement, light-cured 'glass
      ionomer cement', or a combination of glass ionomer cement and composite. The
      corresponding values for the Norwegian dentists were 39.1% and 41.0%,
      respectively, and for the Danish dentists 29.2% and 18.4%. In Scandinavia, the
      leading strategy for occlusal caries seems to be to postpone operative treatment
      until a definite cavity or radiolucency in the outer third of dentin can be
      observed, and to carry out operative treatment only of the part of the fissure
      that is carious. Composite resin is the predominant material of choice in Sweden,
      while in Denmark the majority of dentists preferred amalgam. Composite, or
      composite in combination with glass ionomer cement material, was the choice of
      almost 80% of Norwegian dentists.

PMID- 11318042
TI  - A controlled study of oral self-care and self-perceived oral health in type 2
      diabetic patients.
AB  - A controlled study was carried out in mid-Sweden with the aim of comparing oral
      self-care and self-perceived oral health in 102 randomly sampled type 2 diabetic
      patients with that of 102 age-and-gender-matched non-diabetic controls. Oral
      health variables were also related to glycemic control (HbA1c), duration, anti
      diabetic treatment, and late complications. Questionnaires were used to collect
      data on oral self-care and self-perceived oral health. Diabetes-related variables
      were extracted from medical records. Eighty-five percent of the diabetic subjects
      had never received information about the relation between diabetes and oral
      health, and 83% were unaware of the link. Forty-eight percent believed that the
      dentist/ dental hygienist did not know of their having diabetes. Most
      individuals, but fewer in the diabetic group, were regular visitors to dental
      care and the majority felt unaffected when confronted with dental services. More
      than 90% in both groups brushed their teeth daily and more than half of those
      with natural teeth did proximal cleaning. Subjects in the diabetic group as well
      as in the control group were content with their teeth and mouth (83% vs 85%.
      Those with solely natural teeth and those with complete removable dentures
      expressed most satisfaction. Sensation of dry mouth was common among diabetic
      patients (54%) and subjects with hypertension exhibited dry mouth to a greater
      extent (65%) than those who were normotensive. Our principal conclusion is that
      efforts should be made to give information about diabetes as a risk factor for
      oral health from dental services to diabetic patients and diabetes staff.

PMID- 11318043
TI  - Cytotoxicity of dental glass ionomers evaluated using dimethylthiazol
      diphenyltetrazolium and neutral red tests.
AB  - The purpose of this study was to assess the cytotoxicity of some commonly used
      glass ionomers. Three chemically cured glass ionomers (Fuji II, Lining cement,
      and Ketac Silver) and one light-cured (Fuji II LC) were tested. Extracts of mixed
      non-polymerized materials and polymerized specimens were prepared in accordance
      with ISO standard 10993-12. The polymerized specimens were cured and placed
      either directly in the medium (freshly cured), left for 24 h (aged), or aged plus
      ground before being placed in the medium. The cytotoxicity of extracts was
      evaluated on mouse fibroblasts (L, 929), using dimethylthiazol
      diphenyltetrazolium (MTT) and neutral red (NR) assays. Further, the
      concentrations of aluminum, arsenic and lead were analyzed in aqueous extracts
      from freshly cured and aged samples, and the fluoride levels analyzed in aqueous
      extracts from freshly cured samples. All extracts except that of non-polymerized
      Ketac Silver were rated as severely cytotoxic in both assays. Extracts of
      polymerized material were significantly more cytotoxic than extracts of non
      polymerized material. All freshly cured glass ionomers released aluminum and
      fluoride concentrations far above what is considered cytotoxic (aluminum >0.2 ppm
      and fluoride >20 ppm). Extracts from freshly cured Lining Cement contained the
      highest concentrations of aluminum and fluoride (215 ppm and 112 ppm). Extracts
      from freshly cured Ketac Silver had the lowest concentrations of aluminum and
      fluoride but the highest of lead (100 ppm). It can be concluded that all extracts
      from non-cured, freshly cured, and aged glass ionomers contained cytotoxic levels
      of substances. Curing did not reduce the toxicity significantly.

PMID- 11318044
TI  - A 20-year longitudinal study of subjective symptoms of temporomandibular
      disorders from childhood to adulthood.
AB  - The aims were to study the development over 20 years of reported
      temporomandibular disorders (TMD) symptoms in an epidemiologic sample and to
      analyze possible correlations between these symptoms and some other variables.
      Four hundred and two randomly selected 7-, 11- and 15-year-old subjects were
      originally examined by means of a questionnaire with regard to symptoms of TMD.
      The investigation was repeated after 4 5, 10, and 20 years, using the same
      method. After 20 years, when the original group had reached the age of 27 to 35
      years, 378 individuals (94%) could be traced, and they were sent a questionnaire.
      Three hundred and twenty subjects (80% of the original sample, 85% of the traced
      subjects) completed and returned the questionnaire. There was a substantial
      fluctuation of reported symptoms over the 20-year period. Progression to severe
      pain and dysfunction of the masticatory system was rare. On the other hand,
      recovery from frequent symptoms to no symptoms was also rare. At the last
      examination 13% reported one or more frequent TMD symptom. The prevalence of
      bruxism increased with time, but other oral parafunctions decreased. Women
      reported TMD symptoms and headache more often than men. Correlations between the
      studied variables were mainly weak. The highest correlations found (rs = 0.4-0.5)
      were those between reported tooth clenching and tooth grinding and jaw fatigue.
      It can be concluded that in this epidemiologic sample, followed over 20 years
      from childhood to adulthood, a substantial fluctuation of TMD symptoms was found.
      Severe symptoms were rare, but 1 of 8 subjects reported frequent TMD symptoms at
      the last exam.

PMID- 11318045
TI  - Caries decline before fluoride toothpaste was available: earlier and greater
      decline in the rural north than in southwestern Norway.
AB  - The purpose of this study was to evaluate factors related to caries in 6-17-year
      olds in 2 groups of Norwegian counties between 1966 and 1983. The average number
      of surfaces filled and permanent teeth extracted due to caries declined in the 4
      northern counties from 1967. An increase was recorded in the 7 southwestern
      counties until 1971, then a decline. In the 1960s significantly more surfaces
      were filled and teeth extracted in the north compared to the southwest. Based on
      intra-county comparisons, the decline in surfaces treated was greater in the
      north between 1967 and 1983; 5.4 +/- 0.4 vs 3.7 +/- 0.7, P < 0.01. The averages
      were 1.9 surfaces treated in the north and the southwest in 1983. Higher infant
      mortality, lower percentage of people with completed senior secondary education,
      and more inhabitants per doctor and per dentist in the north indicate a less
      favorable situation than in the southwest. School-based fluoride programs had
      been implemented in both groups from the mid-1960s and around 60% participated
      when fluoride toothpaste became freely marketed in 1971. More fluoride programs
      and more fluoride tablets were available to children in the north; this may
      indicate a preventive attitude among dentists. The decline of caries started at
      different times in different parts of Norway. In the rural north with the most
      unfavorable situation, the decline was greater and started years before fluoride
      toothpaste came on to the market. The early decline may partly be ascribed to the
      school-based fluoride programs, the continued decline to several factors.

PMID- 11318046
TI  - The coupled oscillator model of between-hand coordination in alternate-hand
      tapping: a reappraisal.
AB  - Single and alternating hand tapping were compared to test the hypothesis that
      coordination during rhythmic movements is mediated by the control of specific
      time intervals. In Experiment 1, an auditory metronome was used to indicate a set
      of timing patterns in which a 1-s interval was divided into 2 subintervals.
      Performance, measured in terms of the deviation from the target patterns and
      variability, was similar under conditions in which the finger taps were made with
      1 hand or alternated between the 2 hands. In Experiment 2, the modality of the
      metronome (auditory or visual) was found to influence the manner in which the
      produced intervals deviated from the target patterns. These results challenge the
      notion that bimanual coordination emerges from coupling constraints intrinsic to
      the 2-hand system. They are in accord with a framework that emphasizes the
      control of specific time intervals to form a series of well-defined motor events.

PMID- 11318047
TI  - Motor processes in simple, go/no-go, and choice reaction time tasks: a
      psychophysiological analysis.
AB  - Psychophysiological measures were used to compare the response preparation and
      response execution processes of modified versions of F. C. Donders's (1868/1969)
      classic simple, go/no-go, and choice reaction time tasks. On all measures,
      differences between tasks were minimal prior to test stimulus onset, supporting
      the idea of equivalent motor preparation for the 3 tasks. In addition, the
      psychophysiological measures indicated that the time from the onset of motor
      processing to the keypress response was also approximately constant across tasks.
      These results support the assumption that the mean duration of motor processes
      can be invariant across simple, go/no-go, and choice tasks, at least for the
      present modified versions of these tasks. The findings emphasize the utility of
      psychophysiological measures for both examining preparatory processes preceding
      stimulus onset and for localizing effects on reaction time.

PMID- 11318048
TI  - Interaction of scale and time during object identification.
AB  - On each trial a target object and a fragment of the target (or a control
      stimulus) were presented briefly enough to be integrated together. The stimuli
      were masked, and identification accuracy was measured. The fragments were large
      or small in size scale, and were presented early in processing (fragment before
      target) or late in processing (fragment after target). When presented early,
      large-scale fragments tended to facilitate identification more than small-scale
      fragments, but when presented late, small-scale fragments facilitated more than
      large-scale fragments. Facilitation effects from common feature fragments
      supported the idea of a spatiotemporal dependency, in which the efficiency of
      processing a piece of information depends on other pieces of information that
      have been processed. This is a strong type of global-to-local processing and can
      be interpreted within a structural description framework.

PMID- 11318049
TI  - Combined expectancies: event-related potentials reveal the early benefits of
      spatial attention that are obscured by reaction time measures.
AB  - Visual spatial attention has been likened to a "spotlight" that selectively
      facilitates the perceptual processing of events at covertly attended locations.
      However, if participants have advance knowledge of the likely location of an
      impending target and the likely response it will require, facilitation in
      response performance does not occur for targets at the expected (or attended)
      location that require an unexpected response. Event-related potentials (ERPs)
      were recorded during a discrimination task in which the most likely target
      location and target response were simultaneously cued prior to target onset. The
      ERPs showed evidence of enhanced perceptual-level processing for all targets at
      attended locations. These results suggest that the lack of response facilitation
      for unexpected targets at attended locations is likely due to postperceptual
      processes that are activated by the inclusion of nonspatial stimulus
      expectancies, response expectancies, or both.

PMID- 11318050
TI  - Influence of parafoveal processing on the missing-letter effect.
AB  - According to the parafoveal-processing hypothesis, letters are more often missed
      in function words than in content words because the former are more likely to be
      identified in the parafovea, where letter processing is not available. Contrary
      to previous demonstrations, more omissions occurred in function words than in
      content words when parafoveal processing was not available because words were
      displayed in column format, text was read through a 5-letter window, or words
      were presented 1 at a time on a computer screen. In all experiments, impeding
      parafoveal processing decreased omission rates for function but not for content
      words. In the last experiment, direct monitoring of eye movements revealed that,
      for both fixated and skipped words, letters in function words are missed more
      often than content words. These results are best interpreted within a model
      including the structural precedence hypothesis and stressing the importance of
      visual factors.

PMID- 11318051
TI  - Visual representation of malleable and rigid objects that deform as they rotate.
AB  - Most studies and theories of object recognition have addressed the perception of
      rigid objects. Yet, physical objects may also move in a nonrigid manner. A series
      of priming studies examined the conditions under which observers can recognize
      novel views of objects moving nonrigidly. Observers were primed with 2 views of a
      rotating object that were linked by apparent motion or presented statically. The
      apparent malleability of the rotating prime object varied such that the object
      appeared to be either malleable or rigid. Novel deformed views of malleable
      objects were primed when falling within the object's motion path. Priming
      patterns were significantly more restricted for deformed views of rigid objects.
      These results suggest that moving malleable objects may be represented as
      continuous events, whereas rigid objects may not. That is, object representations
      may be "dynamically remapped" during the analysis of the object's motion.

PMID- 11318052
TI  - The effects of acoustic mismatch and selective listening on repetition deafness.
AB  - Previous research (i.e., M. Miller & D. O. MacKay, 1994, 1996) has suggested that
      repetition deafness (RD), like repetition blindness, is robust to physical
      identity and that it consists in a failure to recall specifically the 2nd of the
      2 critical targets (C1 and C2). However, some confounds due to memory load and
      response biases make available evidence inconclusive. Experiment 1 provided a
      strong test of RD between physically mismatching stimuli using a low memory load
      methodology. In Experiment 2, the same presentation method was combined with a
      selective recall task to find that RD is specific of C2. Experiments 3A and 3B
      showed, through an attentional manipulation, that RD is eliminated when people
      can successfully ignore C1 but not otherwise. It is argued that present data
      favor a perceptual interpretation of the RD. Furthermore, the present results
      support the hypothesis of recognition failure as opposed to the alternative token
      individuation failure hypothesis.

PMID- 11318053
TI  - Intentional and unintentional contributions to nonspecific preparation during
      reaction time foreperiods.
AB  - The nonspecific preparation that follows a warning stimulus (WS) to speed
      responding to an impending imperative stimulus (IS) is generally viewed as a
      strategic, intentional process. An alternative view holds that WS acts as a
      conditioned stimulus that unintentionally elicits a tendency to respond at the
      moment of IS presentation as a result of a process of trace conditioning. These
      views were contrasted as explanatory frameworks for classical effects on reaction
      time of the duration and intertrial variability of the foreperiod, the interval
      between WS and IS. It is shown that the conditioning view accounts for the
      available data at least as well as the strategic view. In addition, the results
      of 3 experiments provide support for the conditioning view by showing that
      unintentional contributions to nonspecific preparation can be dissociated from
      intentional contributions.

PMID- 11318054
TI  - Response-effect compatibility in manual choice reaction tasks.
AB  - This study investigated whether compatibility between responses and their
      consistent sensorial effects influences performance in manual choice reaction
      tasks. In Experiment 1 responses to the nonspatial stimulus attribute of color
      were affected by the correspondence between the location of responses and the
      location of their visual effects. In Experiment 2, a comparable influence was
      found with nonspatial responses of varying force and nonspatial response effects
      of varying auditory intensity. Experiment 3 ruled out the hypothesis that
      acquired stimulus-effect associations may account for this influence of response
      effect compatibility. In sum, the results show that forthcoming response effects
      influence response selection as if these effects were already sensorially
      present, suggesting that in line with the classical ideomotor theory, anticipated
      response effects play a substantial role in response selection.

PMID- 11318055
TI  - Monocular optical constraints on collision control.
AB  - A simulated ball-hitting task was used to explore the optical basis for collision
      control. Ball speed and size were manipulated in Experiments 1 and 2. Results
      showed a tendency for participants to respond earlier to slower and larger balls.
      Early in practice, participants would consistently miss the slowest and largest
      balls. Experiments 3 and 4 examined performance as a function of the range of
      speeds. Performance for identical speeds differed depending on whether the speeds
      were fastest or slowest within a range. Asymmetric transfer between the 2 ranges
      of speeds showed that those trained with slow speeds were very successful when
      tested with a faster range of speeds. Those trained with fast speeds did not do
      as well when tested on slower speeds. The pattern of results across 4 experiments
      suggests that participants were using optical angle and expansion rate as
      separate degrees of freedom for solving the collision task.

PMID- 11318056
TI  - Variability in isochronous tapping: higher order dependencies as a function of
      intertap interval.
AB  - Isochronous serial interval production (ISIP) data, as from unpaced finger
      tapping, exhibit higher order dependencies (drift). This fact has largely been
      ignored by the timing literature, one reason probably being that influential
      timing models assume random variability. Men and women, 22-36 years old,
      performed a synchronization-continuation task with intertap intervals (ITI) from
      0.4 s to 2.2 s. ISIP variability was partitioned into components attributable to
      drift and 1st-order serial correlation, and the results indicate that (a) drift
      contributes substantially to the dispersion for longer ITIs, (b) drift and 1st
      order correlation are different functions of the ITI, and (c) drift exhibits
      break close to 1.0 s and 1.4 s ITI. These breaks correspond to qualitative
      changes in performance for other temporal tasks, which suggests common timing
      processes across modalities and tasks.

PMID- 11318057
TI  - Motor programming during practice conditions high and low in contextual
      interference.
AB  - Random practice has been reported to demand greater time for movement preparation
      during acquisition than blocked practice. The present study revealed that this
      could be attributed to a more complete engagement of the motor programming
      process during random practice. This cost, however, was localized to the motor
      programming subprocess that S. T. Klapp (1995) associated with organizing the
      internal structure of a movement chunk rather than an alternative subprocess
      responsible for organizing movement chunks into the correct serial order. The
      more thorough employment of motor programming during acquisition by random
      practice participants resulted in a more efficient use of this planning operation
      during retention, as well as more accurate movement reproduction. These data
      support the claim that practice conditions high in contextual interference
      support improvements in both movement preparation and memory strength.

PMID- 11318058
TI  - Inertial constraints on limb proprioception are independent of visual
      calibration.
AB  - When the coincidence of a limb's spatial axes and inertial eigenvectors is
      broken, haptic proprioception of the limb's position conforms to the
      eigenvectors. Additionally, when prisms break the coincidence between an arm's
      visual and actual positions, haptic proprioception is shifted toward the visual
      spatial direction. In 3 experiments, variation of the arm's mass distribution was
      combined with prism adaptation to investigate the hypothesis that the
      proprioceptive effects of inertial and visual manipulations are additive. This
      hypothesis was supported across manipulations of plane of motion, body posture,
      proprioceptive target, and proprioceptive experience during prism adaptation.
      Haptic proprioception seems to depend on local, physical reference frames that
      are relative to the physical reference frames for the body's environmental
      position and orientation.

PMID- 11318059
TI  - Recognition of self-generated actions from kinematic displays of drawing.
AB  - Five experiments addressed the question of whether individuals can distinguish
      between self-generated and other-generated actions when seeing their visual
      effects. Each experiment consisted of a recording session in which participants
      drew familiar and unfamiliar characters without receiving visual feedback and a
      recognition session in which they provided self-or-other judgments (SOJs) to
      indicate whether a kinematic display reproduced the visual effects of their own
      actions. The main results were that self-generated and other-generated drawing
      can be distinguished, that the familiarity of character shapes does not influence
      the accuracy of SOJs, and that velocity information is crucial for the
      identification of self-generated drawing. The ability to determine authorship
      from kinematic displays of drawing provides evidence for the contribution of
      action-planning structures to perception.

PMID- 11318060
TI  - The up-right/down-left advantage occurs for both participant- and computer-paced
      conditions: an empirical observation on Adam, Boon, Paas, and Umilta (1998).
AB  - When up and down stimuli are mapped to left and right keypresses or "left" and
      "right" vocalizations in a 2-choice reaction task, performance is often better
      with the up-right/down-left mapping than with the opposite mapping. J. J. Adam,
      B. Boon, F. G. W. C. Paas, and C. Umilta (1998) presented evidence that the up
      right/down-left advantage is obtained when trials are participant paced but not
      when they are computer paced. In all, 3 experiments are reported that show no
      difference in magnitude of the up-right/down-left advantage between computer
      paced and participant-paced conditions. The advantage was eliminated, however, in
      Experiment 3 when a response deadline was imposed. Response speed, rather than
      participant or computer pacing of trials, is crucial.

PMID- 11318061
TI  - Effect of an initiating action on the up-right/down-left advantage for vertically
      arrayed stimuli and horizontally arrayed responses.
AB  - When up and down stimuli are mapped to left and right keypresses or "left" and
      "right" vocalizations in a 2-choice reaction task, performance is often better
      with the up-right/down-left mapping than with the opposite mapping. This study
      investigated whether performance is influenced by the type of initiating action.
      In all, 4 experiments showed the up-right/down-left advantage to be reduced when
      the participant's initiating action was a left response compared with when it was
      a right response. This reduction occurred when the initiating action and response
      were both keypresses, both were spoken location names, and one was a spoken
      location name and the other a keypress. The results are consistent with the view
      that the up-right/down-left advantage is due to asymmetry in coding the
      alternatives on each dimension, and a distinction between categorical and
      coordinate spatial codes seems to provide the best explanation of the advantage.

PMID- 11318062
TI  - Perception and production of brief durations: beat-based versus interval-based
      timing.
AB  - Two experiments examined whether timing of short intervals is beat- or interval
      based. In Experiment 1, subjects heard a sequence of standard tones followed by 2
      test tones; they compared the interval between test tones to the interval between
      the standards. If optimal precision required beat-based timing, performance
      should be best in blocks in which the interval between standard and test reliably
      matched the standard interval. No such effect was observed. In Experiment 2,
      subjects heard 2 test tones and reproduced the intertone interval by producing 2
      keypress responses. Entrainment to the beat was apparent: First-response latency
      clustered around the standard interval and was positively correlated with the
      produced interval. However, responses occurring on or near the beat showed no
      better temporal fidelity than off-beat responses. One plausible interpretation of
      these findings is that the brain always times brief intervals with an interval
      timer; however, this timer can be used in a cyclic fashion to trigger rhythmic
      responses.

PMID- 11318063
TI  - Environmentally defined frames of reference: their time course and sensitivity to
      spatial cues and attention.
AB  - In a Simon task the effects of spatial cues and attention on spatial stimulus
      coding were explored. Participants made speeded responses corresponding to the
      direction of target arrows that were preceded by peripherally presented cues. Cue
      validity varied across experiments as did the percentage of trials on which the
      target appeared peripherally or centrally. The data indicate (a) that targets are
      coded relative to multiple reference frames, (b) that spatial coding of a target
      is not affected when attention is shifted to the target, and (c) that an object
      serves as a referent for spatial coding of other objects even after its spatial
      code no longer activates responses.

PMID- 11318064
TI  - Use of a statistically designed experimental approach to optimize the propylketal
      derivatization of barbiturates.
AB  - The derivatization of barbiturates with dimethylformamide dipropylacetal and
      dimethylformamide diisopropylacetal is studied with respect to the optimization
      of reaction recovery and reliability. A second-order orthogonal experimental
      design is utilized in order to obtain regression equations for the reaction
      recovery dependence on the derivatization solution composition, incubation
      temperature, and time for amobarbital, butalbital, pentobarbital, phenobarbital,
      and secobarbital. Regression equations for the effect of incubation temperature
      and time on the derivative recovery and the optimum conditions for derivatization
      recoveries are obtained. Differences in the phenomena of the derivative formation
      are evaluated between the two derivatizing reagents and the barbiturates. Based
      on the analysis of the obtained equations, it is concluded that the dipropylketal
      derivative of barbiturates is superior in comparison with diisopropylketal when
      considering the milder conditions of the reaction, absence of sudden changes in
      the recovery with a variation in the derivatization parameters, and reliability
      for the simultaneous testing of the barbiturates. A method for the routine
      testing of the barbiturates by gas chromatography-mass spectrometry in urine
      specimens is included.

PMID- 11318065
TI  - Analysis of olive oil and seed oil triglycerides by capillary gas chromatography
      as a tool for the detection of the adulteration of olive oil.
AB  - Individual triglyceride (TG) species of olive oil and several seed oils (corn,
      cottonseed, palm, peanut, soybean, and sunflower) are baseline separated on a
      WCOT TAP CB fused-silica capillary column by capillary gas chromatography (CGC)
      with a flame-ionization detector (FID) and either cold on-column or split
      injection. An adulteration of olive oil with a low content (< 5%) of these seed
      oils (except peanut oil) can be verified by the detection of the increasing
      levels of trilinolein or tripalmitin in olive oil in which these TG species are
      normally absent or present at very low levels (< 0.5%). An adulteration with over
      20% peanut oil can be detected by the increasing levels of palmitodilinolein. TG
      species that can be coeluted with trilinolein in the reversed-phase high
      performance liquid chromatographic (RP-HPLC) mode are baseline separated by the
      CGC technique, and their structures are identified by selective ion monitoring
      mass spectrometry. The following comparisons--the CGC-FID and RP-HPLC methods for
      detection of adulteration, cold on-column and split-injection modes for CGC-FID,
      and silylation or thin-layer chromatography pretreatment and simple dilution of
      one or more of the oil samples--are also presented. The normalized percentage
      area of the TG species is sufficient for the method limits used in this study.
      Mixtures of virgin olive oil with refined or residue olive oil could not be
      distinguished from the virgin type by the method used in this study.

PMID- 11318066
TI  - Thin-layer chromatography-pyrolysis-gas chromatography-mass spectrometry: a
      multidimensional approach to marine lipid class and molecular species analysis.
AB  - A new multidimensional chromatographic method is described in which material
      separated into lipid-class bands on silica-coated quartz thin-layer
      chromatography (TLC) rods (Chromarods) is desorbed using a pyrolysis unit
      interface and introduced directly into a gas chromatograph-mass spectrometer for
      molecular species analysis. Steryl esters, wax esters, hydrocarbons, ketones, and
      fatty-acid methyl esters (FAMEs) are thermally desorbed without pretreatment. In
      order to desorb free sterols, monoacylglycerols (MAGs), aliphatic alcohols, and
      free fatty acids, the esters are converted to trimethylsilyl derivatives on the
      rod. Triacylglycerols and phospholipids are converted to FAMEs by
      thermochemolysis with tetramethylammonium hydroxide. The method's utility is
      demonstrated with lipids from seawater particulate matter by first confirming the
      identity of lipid bands with the appropriate standards. The wax ester-steryl
      ester TLC band contained no more than 8% steryl esters. Wax esters of up to C42
      are detected. In six individual acyl lipid classes, C14-C22 fatty acids are
      detected with C16 acids predominant in all but wax esters. C16-C22 MAGs are
      identified in the complex acetone-mobile polar lipid band. The method
      successfully extends the scope of latroscan TLC-flame-ionization detection on
      Chromarods, which is a widely used technique for lipid-class analysis.
      Modification of the pyrolysis probe to handle intact TLC rods is a future
      objective.

PMID- 11318067
TI  - Solid-phase extraction and high-performance liquid chromatography applied to the
      determination of quinapril and its metabolite quinaprilat in urine.
AB  - Quinapril is an antihypertensive drug that belongs to the family of angiotensin
      converting enzyme inhibitors. It is metabolized to quinaprilat, which is the
      compound that is really responsible for the therapeutic action. In this study, a
      rapid and simple liquid chromatographic method with photometric detection is
      described and applied to the determination of quinapril and quinaprilat in urine.
      The cleanup procedure for the urine samples consists of a solid-liquid extraction
      using C8 cartridges. Under these conditions, both compounds and the internal
      standard (enalapril maleate) are separated in less than 9 min. Recoveries for
      quinapril and quinaprilat are greater than 80%. The method is sensitive enough
      (detection limit of 60 ng/mL for quinapril and 50 ng/mL for quinaprilat) to be
      applied for the determination of quinapril and quinaprilat in urine samples
      obtained from four hypertensive patients after the intake of a therapeutic dose.

PMID- 11318068
TI  - A chromatospectroscopic method for analyzing the signals generated during high
      performance liquid chromatography with diode-array detection.
AB  - A "chromatospectroscopic" technique has been developed to quantitate two
      compounds that coelute in high-performance liquid chromatography. The method uses
      a diode-array detector with Millenium 32 software to extract spectra at regular
      time intervals during the elution of the unique peak and recover spectral data
      (absorbance versus wavelength), which can then be processed using the Excel
      software package. The method is applied to mixtures of two coeluting UV filters.
      Both could be accurately quantitated even when the mixture consisted of 99.5% of
      one and only 0.5% of the other.

PMID- 11318069
TI  - Correlation coefficients of solute relative retentions for pairs of modified
      cyclodextrins: evaluation of selectivity by differently responding gas
      chromatographic stationary phases.
AB  - Relative retention times versus the n-undecane for ten diverse probe solutes from
      volatile oils are scatterplotted between pairs of modified cyclodextrin (CD)
      phases. If the resulting line of best fit has a very high correlation coefficient
      (r), then the two CDs are behaving similarly and will not give different results.
      A low value of r between two CD phases indicates they behave contrastingly enough
      to give different analyses. Presuming a laboratory wants three differently
      behaving commercial CDs, twelve are considered in this way to find the optimum
      three pairings (each showing r to be less than 0.800 with an average of less than
      0.700). These requirements are met by Chiraldex G-DA (gamma-dipentyl) and A-PH
      (alpha-hydroxypropyl, dimethyl) with Beta-Dex 225 (beta-diacetyl,
      butyldimethylsilyl) capillaries. Solutes that fall close to the line of fit
      between two of the phases are undergoing "normal" transient CD molecular
      interaction with both. They may then show extra retention with the third phase on
      the other two plots, which suggests close solute-guest/CD-host molecular fit.
      Another possibility is that this third modified CD may behave merely as a normal
      non-CD phase to such a solute (shown by the rejection of it) with a lower
      retention than is normal. Hierarchical cluster analysis seems unreliable to
      indicate CD-phase relationships.

PMID- 11318070
TI  - What is meant by the term sorption excess and how does it influence reversed
      phase selectivity?

PMID- 11318071
TI  - Osteoarthritis management: the role of cyclooxygenase-2-selective inhibitors.
AB  - BACKGROUND: Cyclooxygenase (COX)-2-selective inhibitors are a new type of
      nonsteroidal anti-inflammatory drug (NSAID) for the management of pain caused by
      osteoarthritis (OA). The most recent OA guidelines from the American College of
      Rheumatology were published in 2000 because new therapies such as the COX-2
      selective inhibitors had been introduced for the management of OA. OBJECTIVE:
      Because more data are now available on efficacy and safety issues with COX-2
      selective inhibitors, NSAIDs, and acetaminophen, this review focuses on how COX-2
      selective inhibitors may change the pharmacologic management of patients with OA.
      METHODS: References were obtained from MEDLINE, BIOSIS, EMBASE, and Internet
      searches of the literature. CONCLUSIONS: The safety and efficacy of two COX-2
      selective inhibitors, rofecoxib and celecoxib, have been examined in a number of
      clinical trials, and these agents have been shown to offer efficacy similar to
      that of NSAIDs. Acetaminophen continues to be the initial drug of choice for the
      management of OA because of its efficacy, safety, cost, and availability. COX-2
      selective inhibitors should be considered in patients with OA who do not respond
      to or cannot tolerate therapy with acetaminophen. COX-2-selective inhibitors have
      an improved gastrointestinal (GI) safety profile compared with traditional NSAIDs
      and should be chosen over NSAIDs if prescription plan access and/or expense is
      not a concern. COX-2-selective inhibitors are clinically indicated for patients
      at increased risk of developing NSAID-induced GI complications, a population in
      whom the use of COX-2-selective inhibitors may be cost-effective because the
      incidence and mortality associated with serious GI adverse events and use of
      expensive GI comedications would be reduced.

PMID- 11318072
TI  - Zanamivir and oseltamivir: two new options for the treatment and prevention of
      influenza.
AB  - BACKGROUND: Influenza infection is responsible for thousands of hospitalizations
      and deaths in the United States each year. Until recently, management options
      were limited to vaccination or use of the antiviral agents amantadine and
      rimantadine. Two antiviral drugs, zanamivir and oseltamivir, have recently been
      approved by the US Food and Drug Administration for the treatment of influenza A
      and influenza B. OBJECTIVE: This article reviews the published data on the
      pharmacology and clinical utility of zanamivir and oseltamivir in the treatment
      and prevention of influenza A and influenza B illness. METHODS: To identify
      relevant literature, a search of MEDLINE, International Pharmaceutical Abstracts,
      and the Iowa Drug Information Service was conducted for the period from 1969 to
      2000. The search terms used were influenza, neuraminidase, zanamivir,
      oseltamivir; amantadine, and rimantadine. The reference lists of the articles so
      obtained were used to identify additional publications. RESULTS: Zanamivir and
      oseltamivir inactivate viral neuraminidase, an enzyme responsible for cleaving
      sialic acid residues on newly formed virions as they bud off from the host cell.
      This inhibition results in aggregation of virions on the surface of the host
      cell, which limits the extent of infection and speeds recovery from illness.
      Clinical studies have shown that neuraminidase inhibitors can decrease the median
      duration of influenza-related symptoms by approximately 1 day if initiated within
      48 hours of the onset of symptoms of influenza. CONCLUSIONS: Evidence supports
      the use of zanamivir and oseltamivir in the treatment of influenza; however,
      additional studies are needed to clarify their utility and tolerability in
      pediatric and high-risk patients, as well as their utility in the prevention of
      influenza.

PMID- 11318074
TI  - Hepatitis B vaccines: assessment of the seroprotective efficacy of two
      recombinant DNA vaccines.
AB  - BACKGROUND: In universal vaccination programs, when there is no postvaccination
      sero-1 logic assessment of response, there must be confidence that the vaccines
      used provide a high degree of seroprotection. OBJECTIVE: This parallel analysis
      of 2 recombinant hepatitis B vaccines (Engerix B and Recombivax/HB-Vax II) was
      conducted to review the seroprotective efficacy of each vaccine in defined
      populations. METHODS: Clinical studies of the 2 vaccines published as manuscripts
      or conference abstracts in the public domain between January 1986 and April 1999
      were identified retrospectively by unrestricted screening of journals through
      BIOSIS, MEDLINE, and EMBASE and the Internet. Unpublished or internal company
      data were excluded to maintain impartiality. The studies were reviewed and
      analyzed. The studies were not assessed for quality other than a judgment of
      their eligibility for inclusion in the analysis. The primary outcome measure was
      the proportion of subjects in defined populations who showed an early
      seroprotective response to currently licensed vaccination schedules. Summary
      statistical analyses of seroprotective response rates and 95% CIs were calculated
      for each vaccine for each population. Seroprotective response was defined by an
      anti-hepatitis B surface antigen titer > or =10 IU/L measured between 1 and 3
      months after the final vaccination. Because the study was designed specifically
      to review published immunogenicity data, safety data were not assessed. The study
      was not designed to demonstrate superiority of one vaccine over the other.
      RESULTS: A total of 181 clinical studies representing 32,904 vaccinated subjects
      were reviewed and analyzed, of whom 24,277 had been vaccinated with Engerix B and
      8627 vaccinated with Recombivax/ HB-Vax II. Seroprotection was achieved in 20,060
      subjects (95.8%) with Engerix B and in 7774 subjects (94.3%) with Recombivax/HB
      Vax II in the normal population vaccinated according to currently licensed 3-dose
      schedules. In a subgroup analysis, response rates in health care workers were
      6492 subjects (94.5%) for Engerix B and 3245 subjects (92.2%) for Recombivax/HB
      Vax II. Children and adolescents (1-19 years) showed the highest response rates
      to vaccination (4612 [98.6%], Engerix B; 2292 [98.9%], Recombivax/HB-Vax II). A
      total of 2875 infants (<1 year) (95.8%) achieved seroprotection with Engerix B;
      701 (88.5%) achieved seroprotection with Recombivax/ HB-Vax II. CONCLUSIONS:
      Hepatitis B vaccination programs using either Engerix B or Recombivax/HB-Vax II
      can achieve high seroprotective response rates, particularly in childhood and
      adolescence. Ideally, younger populations should be a primary target in current
      universal vaccination programs.

PMID- 11318073
TI  - Linezolid: an oxazolidinone antimicrobial agent.
AB  - BACKGROUND: Linezolid is the first oxazolidinone anti-infective agent marketed in
      the United States. It is indicated for the treatment of nosocomial pneumonia,
      complicated skin and skin-structure infections caused by methicillin-sensitive or
      methicillin-resistant Staphylococcus aureus and other susceptible organisms, and
      vancomycin-resistant Enterococcus faecium infections. It also is indicated for
      the treatment of uncomplicated skin and skin-structure infections caused by
      methicillin-sensitive S. aureus or Streptococcus pyogenes, and community-acquired
      pneumonia caused by penicillin-sensitive Streptococcus pneumoniae. OBJECTIVE:
      This article reviews the pharmacologic properties and clinical usefulness of
      linezolid. METHODS: Using the terms linezolid, PNU-100766, and oxazolidinone, we
      performed a literature search of the following databases: MEDLINE (1966 to
      September 2000), HealthSTAR (1993 to September 2000), Iowa Drug Information
      Service (1966 to September 2000), International Pharmaceutical Abstracts (1970 to
      September 2000), PharmaProjects (January 2000 version), and meeting abstracts of
      the Infectious Diseases Society of America and the Interscience Conference on
      Antimicrobial Agents and Chemotherapy (1996 to 2000). RESULTS: Linezolid has a
      unique structure and mechanism of action, which targets protein synthesis at an
      exceedingly early stage. Consequently, cross-resistance with other commercially
      available antimicrobial agents is unlikely. It is primarily effective against
      gram-positive bacteria. To date, resistance to linezolid has been reported in
      patients infected with enterococci. The pharmacokinetic parameters of linezolid
      in adults are not altered by hepatic or renal function, age, or sex to an extent
      requiring dose adjustment. Linezolid is metabolized via morpholine ring
      oxidation, which is independent of the cytochrome P450 (CYP450) enzyme system; as
      a result, linezolid is unlikely to interact with medications that stimulate or
      inhibit CYP450 enzymes. Compassionate-use trials and other clinical studies
      involving mainly adult hospitalized patients with gram-positive infections have
      shown that linezolid administered intravenously or orally is effective in a
      variety of nosocomial and community-acquired infections, including those caused
      by resistant gram-positive organisms. Reported adverse effects include
      thrombocytopenia. diarrhea, headache, nausea, vomiting, insomnia, constipation,
      rash, and dizziness. Preliminary pharmacoeconomic data indicate that a
      significantly higher percentage of patients receiving linezolid therapy versus
      comparator could be discharged from the hospital by day 7 (P = 0.005).
      CONCLUSIONS: Linezolid appears to be effective while maintaining an acceptable
      tolerability profile. Due to the risk of bacterial resistance, linezolid should
      be reserved for the treatment of documented serious vancomycin-resistant
      enterococcal infections.

PMID- 11318075
TI  - Pharmacodynamic and pharmacokinetic properties of a premixed 85/15 human insulin
      preparation.
AB  - BACKGROUND: Many patients with diabetes use mixtures of fast-acting (regular
      human) insulin and intermediate-acting (neutral protamine Hagedorn [NPH]) insulin
      to control their blood glucose levels. Premixed insulin is available in a 70%/30%
      mixture and a 50%/50% mixture of NPH/regular human insulin. For some patients,
      however, a premixed formulation containing > or =30% regular human insulin can
      provide too much fast-acting insulin, potentially causing an increased risk for
      hypoglycemia in the early hours after injection. OBJECTIVE: The pharmacokinetic
      and pharmacodynamic properties of a premixed formulation of 85% NPH insulin and
      15% regular human insulin (85/15) were compared with those of a premixed 70%/30%
      NPH/regular human insulin preparation and 100% NPH insulin. METHODS: A 12-hour
      euglycemic clamp approach was used to assess glucose-lowering effects and serum
      insulin levels in 36 healthy male volunteers in a single-dose (0.5 U/kg),
      randomized, double-blind, 3-period, crossover study. RESULTS: From 0 to 8 hours
      after injection, the glucose-lowering effects and serum insulin levels for the
      85/15 premixed insulin preparation were significantly greater than those for NPH
      insulin (P < or = 0.05) but significantly less than those for the 70/30 premixed
      insulin preparation. The mean (+/- SEM) maximum glucose infusion rate (GIRmax)
      was 8+/-0.6 mg/(min x kg) for the 85/15 preparation, 7+/-0.6 mg/(min x kg) for
      NPH, and 9+/-0.6 mg/(min x kg) for the 70/30 preparation, with time to peak GIR
      (tmax(GIR)) occurring at 313, 360, and 272 minutes, respectively. Time to peak
      insulin levels did not differ significantly for the 3 preparations, but maximum
      serum insulin concentration (Cmax(ins)) was significantly different between the
      groups (70/30 premix: 54+/-2.2 microU/mL; 85/15 premix: 44+/-2.4 microU/mL; NPH:
      35+/-1.7 microU/mL). Glucodynamic effect and serum insulin levels did not differ
      significantly among preparations during the interval from 8 to 12 hours after
      injection. Mean serum C-peptide levels ranged from -0.6 to 1.0 ng/mL for each
      preparation during the 12-hour period after injection. CONCLUSIONS: The 85/15
      premixed insulin preparation demonstrated clinical pharmacokinetic and
      pharmacodynamic properties that were intermediate between, and significantly
      different from, those of NPH insulin and the 70/30 premixed insulin preparation.

PMID- 11318076
TI  - In vitro activity and pharmacodynamics of azithromycin and clarithromycin against
      Streptococcus pneumoniae based on serum and intrapulmonary pharmacokinetics.
AB  - BACKGROUND: Multidrug-resistant strains of Streptococcus pneumoniae are
      increasingly common worldwide, but the clinical significance of their resistance
      to the macrolide antibiotics is controversial. Applying pharmacokinetic and
      pharmacodynamic principles can assist in the selection of appropriate
      antimicrobial therapy. OBJECTIVES: The purpose of this study was to determine the
      in vitro activity of penicillin, azithromycin, clarithromycin, and clindamycin
      against clinical isolates of S. pneumoniae and to evaluate the pharmacodynamics
      of azithromycin and clarithromycin based on serum and epithelial lining fluid
      (ELF) concentrations. METHODS: The minimum inhibitory concentrations (MICs) of
      penicillin, azithromycin, clarithromycin, and clindamycin were determined for 307
      isolates of S. pneumoniae using broth microdilution. Using serum and ELF
      concentrations after standard dosing, we calculated the proportion of isolates
      against which it would be possible to obtain a ratio of azithromycin area under
      the curve to MIC > or =25 and clarithromycin concentrations that exceeded the MIC
      for > or =40% of the dosing interval. RESULTS: Overall, 19.5%, 25.4%, 25.1%, and
      7.2% of the 307 pneumococcal isolates were resistant to penicillin, azithromycin,
      clarithromycin, and clindamycin, respectively. However, 71.7% of penicillin
      resistant strains were also resistant to azithromycin and clarithromycin. Based
      on serum concentrations, clarithromycin achieved its pharmacodynamic target in
      76.9% of isolates, compared with 59.9% for azithromycin. Based on ELF
      concentrations, clarithromycin achieved its pharmacodynamic target in 93.5% of
      isolates, compared with 74.6% for azithromycin. Based on ELF concentrations,
      clarithromycin achieved its pharmacodynamic target in 86.7% of penicillin
      resistant isolates, compared with 28.3% for azithromycin. CONCLUSIONS: On the
      basis of serum and ELF concentrations, clarithromycin achieved pharmacodynamic
      targets against a greater proportion of S. pneumoniae isolates than did
      azithromycin. Clinical studies are needed to determine the efficacy of these
      agents against pneumococci that demonstrate in vitro resistance using current
      susceptibility breakpoints.

PMID- 11318077
TI  - Effectiveness of levofloxacin for adult community-acquired pneumonia caused by
      macrolide-resistant Streptococcus pneumoniae: integrated results from four open
      label, multicenter, phase III clinical trials.
AB  - BACKGROUND: The rate of macrolide resistance among Streptococcus pneumoniae
      clinical isolates is rising. Coresistance to several unrelated classes of
      antimicrobial agents is common and may limit the treatment options available for
      the management of infections caused by this pathogen. Although the
      fluoroquinolones appear to retain activity against macrolide-resistant
      pneumococci, limited clinical data exist to support their use in this setting.
      OBJECTIVE: This study integrated data from 4 clinical trials to determine whether
      the fluoroquinolone levofloxacin is an effective therapeutic agent for community
      acquired pneumonia (CAP) caused by macrolide-resistant S. pneumoniae. METHODS:
      Across the 4 trials, 271 adult patients with CAP were diagnosed with infections
      caused by S. pneumoniae; these constituted the intent-to-treat population.
      Clinical isolates obtained from each patient at admission were tested using broth
      microdilution for in vitro sensitivity to the macrolide erythromycin (minimum
      inhibitory concentration breakpoints: susceptible, < or =0.25 microg/mL;
      intermediate, 0.5 microg/mL; resistant, > or =1.0 microg/mL). All patients
      received levofloxacin (500 mg once daily for 7-14 days) and were analyzed at a
      posttherapy visit (2-5 days after completion of therapy) for clinical and
      microbiologic outcomes; in 3 trials, patients were also examined at a poststudy
      visit (14-28 days after completion of treatment). Clinical and microbiologic
      outcomes were analyzed in patients infected with macrolide-resistant and
      macrolide-susceptible S. pneumoniae. RESULTS: A total of 235 evaluable patients
      infected with S. pneumoniae were identified from the 4 trials. Twenty-seven
      (11.5%) patients were infected with isolates resistant to erythromycin, of whom
      26 (96.3%) were clinical successes. By comparison, the clinical success rate in
      patients infected with erythromycin-susceptible isolates was 97.7%. CONCLUSIONS:
      These results suggest that if future studies demonstrate the clinical relevance
      of macrolide resistance, levofloxacin may be a useful therapeutic option in
      patients with CAP caused by macrolide-resistant S. pneumoniae. However, caution
      may be warranted to prevent overprescription of levofloxacin and other
      fluoroquinolones, given the potential for the development of resistance in S.
      pneumoniae.

PMID- 11318078
TI  - Efficacy and tolerability of timolol maleate ophthalmic gel-forming solution
      versus timolol ophthalmic solution in adults with open-angle glaucoma or ocular
      hypertension: a six-month, double-masked, multicenter study.
AB  - BACKGROUND: Timolol has been formulated in a highly purified gellan gum to
      improve its duration of action. The efficacy of this formulation in short-term
      studies using once-daily dosing has been reported. OBJECTIVE: The purpose of this
      study was to evaluate the efficacy and tolerability of 0.5% timolol maleate
      ophthalmic gel-forming solution (timolol GS) given once daily versus 0.5% timolol
      solution given twice daily in a long-term trial. METHODS: This was a multicenter,
      double-masked, 6-month trial. After a washout of ocular hypotensive medication,
      286 patients with open-angle glaucoma or ocular hypertension were randomly
      assigned in a 2:1 ratio to receive 0.5% timolol GS in both eyes once daily or
      0.5% timolol solution in both eyes twice daily. All patients received a morning
      (9 AM) and evening (9 PM) dose. For patients in the timolol GS group, the evening
      dose consisted of a vehicle only, whereas for patients in the timolol solution
      group, both doses consisted of active drug. Intraocular pressure (IOP) was
      measured at trough (before morning instillation) and peak (2 hours after
      instillation) at follow-up examinations at weeks 2, 4, 8, 12, and 24. Adverse
      events were monitored using patient reports. RESULTS: Of the 286 patients
      randomized, 191 received timolol GS and 95 received timolol solution. Ninety
      three percent of patients (265/286) completed the study. At the end of the
      treatment interval (week 24), the mean decrease in IOP at trough ranged from 5.6
      to 5.9 mm Hg in the timolol GS group and from 6.3 to 6.6 mm Hg in the timolol
      solution group. Similar efficacy was observed at 11 AM (peak). At week 24, the
      difference in mean IOP between treatments was -0.61 mm Hg (95% CI -1.44 to 0.22)
      at trough and -0.79 mm Hg (95% CI -1.77 to 0.20) at peak, indicating no
      significant difference between the 2 timolol formulations. The number of reports
      of blurred vision and tearing was significantly higher in the timolol GS group
      than in the timolol solution group (P = 0.04), whereas burning/stinging was
      reported more frequently in the timolol solution group than in the timolol GS
      group (P = 0.04). At week 12, the decrease in mean heart rate at trough (hour 0)
      was significantly less for patients in the timolol GS group than for those in the
      timolol solution group (-1.1 vs -4.2 bpm; P = 0.024). At week 24 (hour 0), the
      decrease in mean heart rate was less for patients treated with timolol GS by 2.5
      bpm (P = 0.051). The heart rate data at peak (hour 2) was similar to that
      observed at trough at week 12 (-2.7 vs -5.7 bpm; P = 0.006) and week 24 (-3.1 vs 
      4.7 bpm; P = 0.063). The mean change in blood pressure was not significantly
      different between treatments. There were no clinically significant differences
      between the groups in visual acuity, biomicroscopy and ophthalmoscopy results, or
      visual fields. CONCLUSIONS: Timolol 0.5% GS administered once daily was shown to
      be as effective in lowering IOP as the equivalent concentration of timolol 0.5%
      solution administered twice daily in patients with ocular hypertension or open
      angle glaucoma.

PMID- 11318079
TI  - Pharmacokinetic and safety profile of desloratadine and fexofenadine when
      coadministered with azithromycin: a randomized, placebo-controlled, parallel
      group study.
AB  - BACKGROUND: Significant cardiac toxicity has been associated with some older
      antihistamines (eg, terfenadine and astemizole) when their plasma concentrations
      are increased. There is thus a need for a thorough assessment of the cardiac
      safety of newer antihistamine compounds. OBJECTIVE: This study was undertaken to
      assess the effects of coadministration of desloratadine or fexofenadine with
      azithromycin on pharmacokinetic parameters, tolerability, and
      electrocardiographic (ECG) findings. METHODS: Healthy volunteers aged 19 to 46
      years participated in this randomized, placebo-controlled, parallel-group, third
      party-blind, multiple-dose study. Subjects received desloratadine 5 mg once
      daily, fexofenadine 60 mg twice daily, or placebo for 7 days. An azithromycin
      loading dose (500 mg) followed by azithromycin 250 mg once daily for 4 days was
      administered concomitantly starting on day 3. Group 1 received desloratadine and
      azithromycin, group 2 received desloratadine and placebo, group 3 received
      placebo and azithromycin, group 4 received fexofenadine and azithromycin, and
      group 5 received fexofenadine and placebo. RESULTS: The results of the
      pharmacokinetic analysis revealed little change in mean maximum concentration
      (Cmax) and area under the concentration-time curve (AUC) values for desloratadine
      with concomitant administration of azithromycin: Cmax ratio, 115% (90% CI, 92
      144); AUC, ratio 105% (90% CI, 82-134). The corresponding ratios for 3
      hydroxydesloratadine were 115% (90% CI, 98-136) and 104% (90% CI, 88-122),
      respectively. A substantial increase was observed in mean Cmax and AUC values for
      fexofenadine when administered with azithromycin: Cmax, ratio, 169% (90% CI, 120
      237); AUC ratio, 167% (90% CI, 122-229). Compared with the group receiving
      desloratadine and azithromycin, subjects receiving fexofenadine and azithromycin
      also displayed greater variability in pharmacokinetic parameters for the
      antihistamine. Mean Cmax and AUC values of azithromycin were slightly higher when
      administered with desloratadine (Cmax ratio, 131% [90% CI, 92-187]; AUC ratio,
      112% [90% CI, 83-153]) but were lower when given in combination with fexofenadine
      (Cmax ratio, 87% [90% CI, 61-124]; AUC ratio, 88% [90% CI, 65-1201). The most
      common adverse event for all regimens was headache, reported in 20 (22%)
      subjects. All combinations of desloratadine or fexofenadine with and without
      azithromycin were well tolerated, and no statistically significant changes in PR,
      QT, or QT, interval, QRS complex, or ventricular rate were observed. CONCLUSIONS:
      Small increases (<15%) in mean pharmacokinetics of desloratadine were observed
      with coadministration of azithromycin. By contrast, peak fexofenadine
      concentrations were increased by 69% and the AUC was increased by 67% in the
      presence of the azalide antibiotic. Based on the reported adverse-events profile
      and the absence of changes in ECG parameters, the combination of desloratadine
      and azithromycin was well tolerated. This study suggests that desloratadine has a
      more favorable drug-interaction potential than does fexofenadine.

PMID- 11318080
TI  - A comparison of the efficacy and tolerability of titrate-to-goal regimens of
      simvastatin and fluvastatin: a randomized, double-blind study in adult patients
      at moderate to high risk for cardiovascular disease.
AB  - BACKGROUND: Use of cholesterol-lowering regimens has been shown to reduce the
      risk of coronary heart disease (CHD), both in primary and secondary prevention.
      However, there have been few studies of the relative benefits and risks of the
      various cholesterol-lowering agents in patient groups with specific risk factors
      for CHD. OBJECTIVE: The primary goal of this study was to compare the proportions
      of adult patients with primary hypercholesterolemia and a moderate to high risk
      for CHD achieving National Cholesterol Education Program low-density lipoprotein
      cholesterol (LDL-C) goals with titrate-to-goal regimens of simvastatin and
      fluvastatin. METHODS: This was a multicenter, prospective, randomized, double
      blind, parallel-group study enrolling adult patients with type IIa or IIb primary
      hypercholesterolemia, LDL-C levels <6.0 mmol/L (<232.0 mg/dL), and triglyceride
      levels <4.5 mmol/L (<398.6 mg/dL), and either CHD or other atherosclerotic
      disease (the CHD, or high-risk, group), or multiple risk factors for CHD (the
      MRF, or moderate-risk, group). After a 6-week washout period, patients were
      randomized to 18 weeks of treatment at an initial dosage of simvastatin 10 mg
      once daily or fluvastatin 20 mg once daily. At 6- and 12-week titration visits,
      the dosage in patients who had not acheived the LDL-C goal could be increased to
      simvastatin 20 mg once daily and then 40 mg once daily, or to fluvastatin 40 mg
      once daily and then 40 mg twice daily. Lipid profiles were obtained at each
      titration visit and at the end of treatment. In addition to the comparison
      between treatments, secondary comparisons were made between the CHD and MRF
      subgroups within each treatment group. Statistical significance was assessed
      using analysis of variance. RESULTS: A total of 478 patients were enrolled, 237
      in the simvastatin group and 241 in the fluvastatin group. There were no
      significant between-group differences in patients' characteristics at baseline.
      At the end of the study, 60.8% (135/222) of patients in the simvastatin group had
      reached target LDL-C goals, compared with 35.1% (76/216) in the fluvastatin group
      (P < 0.001). In the simvastatin CHD and MRF subgroups, 49% and 73%, respectively,
      reached the LDL-C target, compared with 19% and 50% in the corresponding
      fluvastatin subgroups (P < 0.001). The proportion of patients requiring titration
      was higher in the fluvastatin group than in the simvastatin group (87.1% and
      64.1%, respectively; P = 0.001). The incidence of adverse events was similar
      between groups. CONCLUSION: In this study, more patients with primary
      hypercholesterolemia and CHD or multiple risk factors for CHD reached LDL-C goals
      with simvastatin treatment and required less titration than those who received
      fluvastatin treatment.

PMID- 11318081
TI  - Borrowing from other disciplines.

PMID- 11318082
TI  - Dealing with skewed data: an example using asthma-related costs of medicaid
      clients.
AB  - BACKGROUND: Cost data often are nonnormally distributed due to a few very high
      cost values that may not necessarily be dismissed as outliers. Researchers have
      not reached agreement on how to appropriately deal with skewed cost data.
      OBJECTIVES: This study presents an example of skewed cost data that were
      collected retrospectively from the Texas Medicaid database. Common methods of
      dealing with skewed cost distributions are discussed. Data were analyzed using
      various methods, and the statistical results of each test were compared. METHODS:
      Prescription and medical claims data extracted from the Texas Medicaid database
      were analyzed using the Mann-Whitney U test and t tests of untransformed, log
      transformed, and bootstrapped data. RESULTS: All distributions of the
      untransformed cost data were nonnormally distributed, and comparison groups had
      unequal variances. The Mann-Whitney U test negated the effect of the high-cost
      patients and gave a significant result for overall cost differences between
      groups, but in the opposite direction of the mean. The t tests on raw data and
      log-transformed data may not have been optimal because distributions of both raw
      costs and log-costs were nonnormal. CONCLUSIONS: The bootstrap method does not
      need to meet the assumptions of normality and equal variances. In analyses of
      small sample sizes with skewed cost data, the bootstrap method may offer an
      alternative to the more traditional nonparametric or log-transformation
      techniques.

PMID- 11318083
TI  - Acute exacerbation of chronic bronchitis: disease-specific issues that influence
      the cost-effectiveness of antimicrobial therapy.
AB  - BACKGROUND: Acute exacerbation of chronic bronchitis (AECB) is a common
      condition, with substantial associated costs and morbidity. Research efforts have
      focused on innovations that will reduce the morbidity associated with AECB.
      Health care payers increasingly expect that the results of evidence-based
      economic evaluations will guide practitioners in their choice of cost-effective
      interventions. OBJECTIVES: To provide a framework on which to base effective and
      efficient antimicrobial therapy for AECB, we present a concise clinical review of
      AECB, followed by an assessment of the available data on the economic impact of
      this disease. We then address several AECB-specific issues that must be
      considered in cost-effectiveness analyses of AECB antimicrobial interventions.
      METHODS: Published literature on the clinical and economic impact of AECB was
      identified using MEDLINE, pre-MEDLINE, HealthSTAR, CINAHL, Current Contents/All
      Editions, EMBASE, and International Pharmaceutical Abstracts databases. Other
      potential sources were identified by searching for references in retrieved
      articles, review articles, consensus statements, and articles written by selected
      authorities. RESULTS: In evaluating cost-effectiveness analyses of AECB
      antimicrobial therapy it is critical to (1) use the disease-free interval as an
      outcome measure, (2) evaluate the sequence of multiple therapies, (3) address the
      impact of both current and future antibiotic resistance, and (4) measure all
      appropriate AECB-associated costs, both direct and indirect. CONCLUSIONS:
      Incorporating these approaches in economic analyses of AECB antimicrobial therapy
      can help health care organizations make evidence-based decisions regarding the
      cost-effective management of AECB.

PMID- 11318084
TI  - Effect of reduced-dose amprenavir in combination with lopinavir on plasma levels
      of amprenavir in patients infected with HIV.

PMID- 11318085
TI  - Antihypertensive effects of losartan and candesartan.

PMID- 11318086
TI  - A national system to support a mandated PGY-1 year: how to get there from here.

PMID- 11318087
TI  - Tutor and student perceptions of the tutor's role in problem-based learning.
AB  - The role of the tutor in problem-based learning (PBL) differs dramatically from
      the traditional teaching role with which dental students and faculty are
      familiar. In this investigation, the dimensionality and complexity of the tutor
      role were assessed by first- and second-year dental students and by the tutors
      themselves using a twenty-four-item Likert-type questionnaire that served as one
      component of a comprehensive web-based assessment tool, the PBL-Evaluator.
      Evaluations were completed after each PBL case over a period of one and a half
      years by one class of students and for half a year by a second class. Exploratory
      principal components analyses of the responses to the questionnaire revealed a
      more complex factor structure for tutors than for students. While a five-factor
      solution was required for the tutors, a simpler two-factor solution sufficed for
      both groups of first-year students, and a three-factor solution was necessary for
      the second-year students. Although tutors displayed a more nuanced perspective on
      their performance than did students, items related to tutor modeling of
      professional conduct within tutorials consistently emerged as important for both.

PMID- 11318088
TI  - Perceived sources of stress among dental students at the University of Jordan.
AB  - This study investigated perceived stress by dental students at the University of
      Jordan. Two hundred sixty-six students out of 290 completed a modified DES
      questionnaire. The stressors producing the highest ratings for perceived stress
      were examinations and grades, fully loaded day, and lack of time for relaxation.
      For the clinical years, patients' being late or not showing for their
      appointments and completing clinical requirements were also substantial
      stressors. Significant differences were found for eleven items across all classes
      and five items across clinical years. The overall perception of stress by
      students who had medicine as their first choice for admission was higher than for
      students who had dentistry as their first choice. Male-female comparison revealed
      significant differences for five items; between classes, significant differences
      were accounted for by three items. Comparison with earlier studies on identical
      questionnaire items revealed that perception of stress by Jordanian dental
      students was higher than for other students for items relating to educational
      environment and personal or cultural aspects.

PMID- 11318089
TI  - Effectiveness of an online course in dental terminology.

PMID- 11318090
TI  - Revisiting the attitudes of dental faculty toward individuals with AIDS.

PMID- 11318091
TI  - Application of an oral health-related quality of life model to the dental hygiene
      curriculum.

PMID- 11318092
TI  - Founding a new dental school at Nova Southeastern University.
AB  - The dental school arose from the premise that a dental school would round out the
      university and add prestige to the burgeoning Health Professions Division with
      its five schools and eight health programs. The school was founded in light of
      the following circumstances. Patient Pool Evaluation of community facilities and
      services revealed that there was an increasing patient pool, without disturbing
      the present mix. There was evidence of a need for dental care for large numbers
      of unserved or underserved people. Financial Considerations Proforma and cash
      flow budget projections showed financial stability of this project. The
      university was recognized to have the ability to absorb initial capital costs.
      HPD had a history of the success in functioning with tuition-dependent budgets.
      University Factors The university has had success in establishing and operating
      five health professions schools. A complete and experienced infrastructure has
      existed for sixteen years in the University and in the Health Professions
      Division. The university would provide unconditional administrative support.

PMID- 11318093
TI  - Strategies for enhancing the diversity of the oral health profession.

PMID- 11318094
TI  - Genetically controlled expression of surface variant antigens in free-living
      protozoa.

PMID- 11318095
TI  - L-arginine effects on Na+ transport in M-1 mouse cortical collecting duct cells-
      a cationic amino acid absorbing epithelium.
AB  - The effect of L-arginine on transepithelial ion transport was examined in
      cultured M-1 mouse renal cortical collecting duct (CCD) cells using continuous
      short circuit current (Isc) measurements in HCO3-/CO2 buffered solution. Steady
      state Isc averaged 73.8 +/- 3.2 microA/cm2 (n = 126) and was reduced by 94 +/-
      0.6% (n = 16) by the apical addition of 100 microM amiloride. This confirms that
      the predominant electrogenic ion transport in M-1 cells is Na+ absorption via the
      epithelial sodium channel (ENaC). Experiments using the cationic amino acid L
      lysine (radiolabeled) as a stable arginine analogue show that the combined
      activity of an apical system y+ and a basal amino acid transport system y+L are
      responsible for most cationic amino acid transport across M-1 cells. Together
      they generate net absorptive cationic amino acid flux. Application of L-arginine
      (10 mM) either apically or basolaterally induced a transient peak increase in Isc
      averaging 36.6 +/- 5.4 microA/cm2 (n = 19) and 32.0 +/- 7.2 microA/cm2 (n = 8),
      respectively. The response was preserved in the absence of bath Cl- (n = 4), but
      was abolished either in the absence of apical Na+ (n = 4) or by apical addition
      of 100 microM amiloride (n = 6). L-lysine, which cannot serve as a precursor of
      NO, caused a response similar to that of L-arginine (n = 4); neither L-NMMA (100
      microM; n = 3) nor L-NAME (1 mM; n = 4) (both NO-synthase inhibitors) affected
      the Isc response to L-arginine. The effects of arginine or lysine were replicated
      by alkalinization that mimicked the transient alkalinization of the bath solution
      upon addition of these amino acids. We conclude that in M-1 cells L-arginine
      stimulates Na+ absorption via a pH-dependent, but NO-independent mechanism. The
      observed net cationic amino acid absorption will counteract passive cationic
      amino acid leak into the CCD in the presence of electrogenic Na+ transport,
      consistent with reports of stimulated expression of Na+ and cationic amino acid
      transporters by aldosterone.

PMID- 11318096
TI  - ED50 G(Na) block predictions for phenyl substituted and unsubstituted n-alkanols.
AB  - To study the role the phenyl group plays in producing local anesthetic block, a
      sequence of n-alkanols and phenyl-substituted alkanols (phi)-alkanols) were
      characterized in their ability to block Na channels. The sequence of n-alkanols
      studied possess 3-5 carbons (propanol-pentanol). The action of phenol and 3-phi
      alkanols (benzyl alcohol, phenethyl alcohol, 3-phenyl-1-propanol) were also
      studied. Na currents (INa) were recorded from single frog skeletal muscle fibers
      using the Vaseline-gap voltage clamp technique. INas were recorded prior to,
      during, and following the removal of the solutes in Ringer's solution. All
      alkanols and phenol acted to block INa in a dose-dependent manner. Effective
      doses to produce half block (ED50) of INa or Na conductance (GNa) were obtained
      from dose-response relations for all solutes used. The block of GNa depended on
      voltage, and could be separated into voltage-dependent and -independent
      components. Each solute acted to shift GNa-V relations in a depolarized direction
      and reduce the maximum GNa and slope of the relation. All solutes acted to speed
      up INa kinetics and cause hyperpolarizing shifts in steady-state inactivation.
      The magnitude of the kinetic changes increased with dose. Size was an important
      variable in determining the magnitude of the changes in INa; however, size alone
      was not sufficient to predict the changes in INa. ED50s for GNa and AP block
      could be predicted as a function of intrinsic molar volume, hydrogen bond
      acceptor basicity (beta) and donor acidity (alpha), and polarity (P) of the
      solutes. The equivalency of ED50 predictions for AP and GNa block can be
      explained by the fact that AP block arises from channel block and solute-induced
      changes in INa kinetics. phi-Alkanols were more effective at blocking and
      inactivating Na channels than their unsubstituted counterparts. Phenyl
      substituted alkanols are more likely to interact with the channel than their
      unsubstituted counterparts.

PMID- 11318097
TI  - ED50 AP block predictions for phenyl substituted and unsubstituted n-alkanols.
AB  - A series of n-alkanols and phenyl-substituted n-alkanols (phi-alkanols) of
      increasing chain length and phenol were characterized for their ability to block
      action potentials (APs) in frog sciatic nerves. APs were recorded using the
      single sucrose-gap method. The degree of AP attenuation when the nerve was
      exposed to different concentrations of an alcohol was used to construct dose
      response curves. The reciprocals of the half-blocking doses (ED50s) were used to
      obtain a measure of the potency of the alcohols. For n-alkanols and phi-alkanols,
      increasing the chain length by the addition of a methylene group increased the
      potency on average by 3.1 for both groups of alkanols. The addition of a phenyl
      group caused a potency increase that ranged between the values of 77 and 122. The
      ED50 for both groups of alkanols could not be solely predicted by the log octanol
      water partition coefficient (Kow). Using linear solvation energy relations
      (LSER), the log ED50 could be described as a linear combination of the intrinsic
      (van der Waals) molar volume (VI), polarity (P), and hydrogen bond acceptor
      basicity (beta) and donor acidity (alpha). Size alone could not predict the ED50
      for both n-alkanols and phi-alkanols. The results are consistent with the
      hypothesis that alkanols bind to and interact with Na channels to cause AP block.
      Phenyl group addition to an alkanol markedly increases the molecule's potency.

PMID- 11318098
TI  - Temperature-dependent expression of a squid Kv1 channel in Sf9 cells and
      functional comparison with the native delayed rectifier.
AB  - SqKv1A is a cDNA that encodes a Kv1 (Shaker-type) alpha-subunit expressed only in
      the giant axon and the parental giant fiber lobe (GFL) neurons of the squid
      stellate ganglion. We incorporated SqKv1A into a recombinant baculovirus for
      expression in the insect Sf9 cell line. Whole-cell patch-clamp recordings reveal
      that very few cells display functional potassium current (IK) if cultured at the
      standard postinfection temperature of 27 degrees C. At 18 degrees C, less SqKv1A
      protein is produced than at 27 degrees C, but cells with IK currents are much
      more numerous and can survive for at least 20 days postinfection (vs.
      approximately 5 days at 27 degrees C). Activation and deactivation kinetics of
      SqKv1A in Sf9 cells are slower (approximately 3- and 10-fold, respectively) than
      those of native channels in GFL neurons, but have similar voltage dependencies.
      The two cell types show only subtle differences in steady-state voltage
      dependence of conductance and inactivation. Rates of IK inactivation in 20 mM
      external K are identical in the two cell types, but the sensitivity of
      inactivation to external tetraethylammonium (TEA) and K ions differ: inactivation
      of SqKv1A in Sf9 cells is slowed by external TEA and K ions, whereas inactivation
      of GFL IK is largely insensitive. Functional differences are discussed in terms
      of factors that may be specific to cell-type, including the presence of presently
      unidentified Kv1 subunits in GFL neurons that might form heteromultimers with
      SqKv1A.

PMID- 11318099
TI  - Modulation of voltage-dependent K+ channel current in vascular smooth muscle
      cells from rat mesenteric arteries.
AB  - Voltage-dependent K+ (Kv) channels were studied in smooth muscle cells (SMCs)
      freshly isolated from rat mesenteric arteries. A delayed outward rectifier Kv
      current (IK) with a weak voltage dependence was identified. The amplitude of IK,
      but not its inactivation kinetics, was inhibited by 4-aminopyridine (4-AP) (IC50,
      5.1 +/- 0.9 mM). The inhibitory effect of 4-AP was not use-dependent, and the
      unbinding of 4-AP from IK channels was complete in the absence of depolarization
      stimuli, suggesting the binding of 4-AP to the closed state of Kv channels. There
      was no change in the steady-state inactivation, but the steady-state activation
      curve of IK was shifted in the presence of 4-AP by +6 mV. Including 4-AP in
      pipette solution instantly inhibited IK upon the rupture of cell membrane,
      indicating that 4-AP bound to the inner mouth of Kv channel pores. Several Kv
      channel proteins encoding the native IK-type Kv channels, but not the transient
      outward A-type Kv channels, were identified. Among the identified IK-encoding
      gene transcripts, the expression of Kv1.5 was the most abundant. Our results
      elucidate the modulating mechanisms for the 4-AP-induced IK inhibition in rat
      mesenteric artery SMCs and suggest that the unique properties of Kv channels in
      these cells might be related to the heteromeric expression of the IK-encoding
      genes with Kv1.5 subunit playing an important role.

PMID- 11318100
TI  - Open channel-like behavior of reduced carrier models.
AB  - Previous theoretical analyses have demonstrated that some extended channel models
      can exhibit carrier kinetics, even for the case of models where the transporter
      does not experience any conformational change. The purpose of this work is to
      explore the inverse situation, that is, the finding of channel-like transport
      properties in well-defined carrier models. This approximate behavior has been
      previously encountered for the case that rapid equilibrium is established between
      the empty carrier states. This study explores another situation in which a
      typical carrier can exhibit open channel-like kinetic properties, namely, the
      reduction of a classical four-state simple carrier model for the case that one of
      the empty states is a transient intermediate. For this case I analyze here if,
      for some conditions, the kinetics of the three-state reduced model can be
      satisfactorily approximated by a channel description. The analysis performed here
      derives conditions under which this reduced model exhibits channel-like transport
      kinetics. The work is illustrated by the numerical studies of two comparative
      examples: one corresponding to a carrier satisfying the necessary conditions for
      the channel-like behavior, and another for a carrier not meeting those
      conditions. The finding that a well-defined carrier model may exhibit channel
      like transport properties represents a further argument in favor of the concept
      that typical channels and carriers are particular cases of more general
      mechanisms of facilitative transport.

PMID- 11318101
TI  - Characterization of the amyR gene encoding a transcriptional activator for the
      amylase genes in Aspergillus nidulans.
AB  - The Aspergillus nidulans amyR gene and its cDNA were cloned and sequenced. The
      genomic gene comprised 2,092 bp, interrupted by two short introns, and encoded a
      cys-6 zinc transcriptional activator (AMYR) of 662 amino acid residues with a
      calculated molecular mass of 72,862 Da. Disruption of the amyR gene caused
      defects in the utilization of maltose and starch and abolished expression of the
      taaG2 gene encoding A. oryzae Taka-amylase A, which is inducibly and abundantly
      expressed in the wild-type A. nidulans. Expression of the amyR gene was under the
      control of the carbon catabolite repressor, CREA. The growth defect of the malA1
      mutant on maltose was complemented by the amyR gene; and the amyR gene derived
      from the mutant possessed a single mutation, from A to T, at position 1,483,
      resulting in a substitution of His478 to Leu. These results indicate that the
      amyR gene is identical to the genetically defined malA gene. AMYR possessed five
      domains (Zn and MH1-MH4) homologous to Mal63p, a transcriptional activator for
      the genes involved in maltose utilization in Saccharomyces cerevisiae. The His478
      to Leu substitution lay within the MH3 domain, corresponding to the negative
      regulatory domain of Mal63p which relieves the inhibitory effect on the
      activation function in response to maltose.

PMID- 11318102
TI  - The chromosomal region containing pab-1, mip, and the A mating type locus of the
      secondarily homothallic homobasidiomycete Coprinus bilanatus.
AB  - In this paper we describe the cloning of the DNA region containing the A1 mating
      type genes of the secondarily homothallic mushroom Coprinus bilanatus and compare
      its organization to that of heterothallic homobasidiomycetes. As in other
      species, the C. bilanatus A factor contains several different genes that encode
      two different types of homeodomain transcription factor (HD1 and HD2); and some
      of these genes are active in the heterologous host C. cinereus. The HD1 and HD2
      genes are distributed over two closely linked subloci, Aalpha and Abeta. A gene
      coding for a mitochondrial intermediate peptidase (mip) directly flanks the
      Aalpha sublocus. The pab-1 gene, required for para-aminobenzoic acid synthesis,
      is found 39 kb upstream of mip. The structural arrangement of this chromosomal
      region closely resembles the heterothallic C. cinereus. In contrast, the Aalpha
      and Abeta subloci of Schizophyllum commune are further separated, with pab-1
      located between the two subloci, suggesting that a translocation event may have
      occurred during evolution.

PMID- 11318103
TI  - Sequence of Crm1/exportin 1 mutant alleles reveals critical sites associated with
      multidrug resistance.
AB  - We have previously shown that genes involved in a novel pathway of multidrug
      resistance (MDR) in the fission yeast Schizosaccharomyces pombe are functionally
      conserved in human cells (V. Spataro et al. (1997) J Biol Chem 272: 30470-30475).
      The human homologue of one of these genes, hCRM1, has recently been identified
      and found to function in nucleocytoplasmic export, a process which controls the
      subcellular localization and hence activity of a number of key cell cycle
      regulators and transcription factors. Several mutant alleles of crm1 confer a
      phenotype of MDR in S. pombe, through the nuclear accumulation of the AP-1
      transcription factor Pap1. We therefore sequenced mutations of crm1 in fission
      yeast in order to guide the search for analogous hCRM1 mutations which could play
      a role in tumour-drug resistance. Fifteen yeast crm1 mutants were assessed by PCR
      and DNA sequencing. Four mis-sense mutations were identified in the open reading
      frame, three of which (G to A transitions at nucleotide positions 385, 895 and
      1,288) were capable of conferring the MDR phenotype alone. For three of the four
      mutations found, the corresponding amino acid changes affect residues which are
      conserved in the human homologue hCRM1 and lie in highly conserved regions of the
      CRM1 protein. We analysed the corresponding hCRM1 coding regions by RT-PCR and
      sequencing in a panel of ten tumour cell lines, including three ovarian lines
      resistant either to cisplatin or paclitaxel, or to both and one MDR breast cancer
      cell line with nuclear accumulation of the transcription factor YB-1. No hCRM1
      mutations were found in the three cDNA fragments examined in this panel of tumour
      cell lines. However, the identification of amino acid residues within the CRM1
      protein that are critical for the export of the MDR-associated transcription
      factor Pap1 in fission yeast can guide further analysis of hCRM1 mutations in
      tumours with a MDR phenotype.

PMID- 11318104
TI  - A type 2A protein phosphatase gene from Aspergillus nidulans is involved in
      hyphal morphogenesis.
AB  - A PCR-based approach, using degenerate oligonucleotide primers, was used to
      isolate fragments of two genes encoding type 2A protein phosphatases from the
      filamentous fungus, Aspergillus nidulans. The complete genomic sequence of one of
      these genes, pphA, was isolated and characterised. The pphA gene was predicted to
      encode a 329-residue protein which is about 85% identical to mammalian protein
      phosphatase 2A. Ectopic expression of the wild-type pphA+ gene slightly inhibited
      growth in some transformants; but a mutant form of pphA, in which R259 was
      mutated to Q, led to slow growth, delayed germ tube emergence and mitotic defects
      at low temperature. These results indicate that the pphA+ gene plays an important
      role in hyphal growth.

PMID- 11318105
TI  - Transformation of the cultivated mushroom Agaricus bisporus (Lange) using T-DNA
      from Agrobacterium tumefaciens.
AB  - Agrobacterium tumefaciens is known to transfer parts of its tumor-inducing
      plasmid, the T-DNA, to plants, yeasts and filamentous fungi. We have used this
      system to transform germinating basidiospores and vegetative mycelium of a
      commercial strain of the cultivated basidiomycete Agaricus bisporus. Analysis of
      transformants shows that the T-DNA integrates at random sites into the host
      genome and that the selection marker is stable during mitosis and meiosis. The
      Agrobacterium system allows the transformation of both homokaryons and
      heterokaryons of A. bisporus. Also, both karyotypes of an heterokaryon can be
      transformed simultaneously. Furthermore, this is the first report on the
      transformation of vegetative mycelium of a commercial strain of A. bisporus.

PMID- 11318106
TI  - A nucleus-encoded suppressor defines a new factor which can promote petD mRNA
      stability in the chloroplast of Chlamydomonas reinhardtii.
AB  - Mutations in the Chlamydomonas reinhardtii nuclear gene MCD1 specifically
      destabilize the chloroplast petD mRNA, which encodes subunit IV of the cytochrome
      b6/f complex. The MCD1 gene product is thought to interact with the mRNA 5' end
      to protect it from degradation by a 5' --> 3' exoribonuclease and may also have a
      role in translation initiation. Here we report the isolation and characterization
      of a semidominant, allele-specific, nucleus-encoded suppressor of the mcd1-2
      mutation. The suppressor mutation, which defines a new locus MCD2, allows
      accumulation of 10% of the wild-type level of petD mRNA and as much as 50% of the
      wild-type subunit IV level. Taken together, these results suggest the suppressor
      mutation restores photosynthetic growth by stabilizing petD mRNA. In addition, it
      may promote increased translational efficiency, an inference supported by direct
      measurements of the subunit IV synthesis rate. Thus, both MCD1 and MCD2 may
      participate in both chloroplast RNA stability and translation initiation.

PMID- 11318107
TI  - Chloroplast transformation in Euglena gracilis: splicing of a group III twintron
      transcribed from a transgenic psbK operon.
AB  - The Escherichia coli aadA gene product, which confers resistance to spectinomycin
      and streptomycin, has been widely used as a dominant selectable marker for
      chloroplast transformation of Chlamydomonas and tobacco. An aadA transformation
      cassette was adapted for expression in Euglena gracilis chloroplasts by replacing
      the Chlamydomonas promoter and 3' untranslated region (UTR) with the E. gracilis
      psbA promoter and 3' UTR. Transgenic DNA was introduced into E. gracilis
      chloroplasts by biolistic transformation. Streptomycin- and spectinomycin
      resistant colonies were obtained, which screened positively for the presence of
      the transforming vector by PCR amplification. Although integration of the
      transforming DNA into the chloroplast genome was not detected, transforming DNA
      was stably maintained in the chloroplast as an episomal element during continuous
      selection on antibiotics. The aadA cassette was also inserted into a
      transformation vector which contained the independently expressed psbK operon
      from either E. gracilis or a closely related species, E. stellata. The psbK
      operon contained at least two group III introns and a group III twintron, was
      highly expressed, and was only 1.5 kb in length. In transgenic E. gracilis
      chloroplasts, a truncated E. stellata psbK operon was transcribed, and the
      resultant pre-mRNA was accurately spliced. This system should allow the first
      direct analysis of group II and group III intron-splicing mechanisms. In
      addition, it could prove useful in the study of many other Euglena transcription
      and processing events.

PMID- 11318108
TI  - Phage display selection of a peptide DNase II inhibitor that enhances gene
      delivery.
AB  - BACKGROUND: Nuclease activity is thought to be a significant barrier to effective
      gene delivery employing synthetic vectors. In particular, the lysosomal DNase,
      DNase II, has significant access to plasmid DNA, when the protective condensing
      agent has been shed. Here, we present the identification of a peptide DNase II
      inhibitor, enabling enhanced levels of gene delivery. METHODS: A DNase II
      inhibitor was identified by phage display from a cyclic, random 12-amino acid
      library. Activity was assayed by inhibition of DNase II degradation of DNA.
      Transfection enhancement levels were measured over a range of DNA doses with CV-1
      and MDBK cell types using PEI and cationic lipoplexes as vectors. RESULTS: We
      postulated that a DNase II inhibitor would enhance transfection by enabling a
      larger fraction of plasmid DNA to traffic through the cell and enter the nucleus.
      Peptides based on the selected sequence (SLRLLQWFLWAC) [ID2] were shown to
      inhibit DNase II with an observed KI,app of 0.2-2 microM. Lipoplex-mediated
      transfection in vitro was found to be enhanced by ID2-3 across the entire range
      of plasmid DNA doses examined (0.10-3.0 microg/mL). Transfection with PEI/DNA
      complexes was found to be specifically enhanced in the presence of ID2 peptides,
      with a saturable DNA-dose curve as would be expected for a competitive inhibitor.
      Transfection enhancements as high as 270-fold were found in the presence of ID2
      3. CONCLUSIONS: A novel peptide DNase II inhibitor has been used to increase
      transfection. The level of enhancement was found to be significant in multiple
      cell types with multiple synthetic vectors.

PMID- 11318109
TI  - Enhanced in vitro and in vivo cationic lipid-mediated gene delivery with a
      fluorinated glycerophosphoethanolamine helper lipid.
AB  - BACKGROUND: One of the main drawbacks of synthetic, non-viral gene vectors is
      their relatively low in vivo efficiency when compared with viral vectors. The
      present paper describes the use of a partially fluorinated
      glycerophosphoethanolamine (F-PE), a close analog of DOPE, which, as a helper
      lipid with the cationic lipopolyamine pcTG90, increases its in vitro and in vivo
      gene transfer capability to a larger extent than DOPE. METHODS: To evaluate the
      contribution of F-PE to lipoplex-mediated gene transfer, the effect of including
      F-PE in lipoplexes formulated with the lipopolyamine pcTG90 for various
      pcTG90/DOPE/F-PE molar ratios [1:(1-x): x; 1:(2-y):y] was examined. For the in
      vitro analyses on human lung carcinoma epithelial A549 cells, the lipoplexes were
      formulated with the luciferase reporter plasmid pTG11033 using various N/P ratios
      (from 10 to 0.8, N = number of pcTG90 amines, P = number of DNA phosphates). The
      in vivo analyses were performed (1) with the luciferase reporter plasmid pCMV
      Luc, which gives higher luciferase expression in the lung than pcTG11033; (2)
      with pcTG90/co-lipid(s) (1:2) lipoplexes which yield higher expression than the
      (1:1) formulations; and (3) by intravenous (iv) injection into the tail vein of
      mice. RESULTS: The efficiency of the F-PE lipoplexes to transfect in vitro A549
      cells was significantly higher (5-90-fold) than that of DOPE lipoplexes, when
      formulated in HEPES. However, when formulated in 5% glucose, both co-lipids
      display a comparable transfection helper potential. Most remarkably, an up to
      eight-fold increase of luciferase expression could be measured in the lung after
      iv injection of pcTG90/F-PE (1:2) N/P 5 lipoplexes as compared with the
      pcTG90/DOPE lipoplexes. It led also to higher luciferase expression than
      PEI(ExGen500)/pCMV-Luc N/P 10 polyplexes. Besides expression in lung, low levels
      of luciferase expression were also observed in heart, spleen and liver.
      CONCLUSION: The present work, showing a higher in vitro and in vivo transfection
      potential for lipoplexes formulated with a partially fluorinated co-lipid as
      compared with its analogous DOPE lipoplexes or PEI polyplexes, indicates that
      'fluorinated' lipoplexes are attractive candidates for in vivo applications.

PMID- 11318110
TI  - Transfection of epithelial cells is enhanced by combined treatment with mannitol
      and polyethyleneglycol.
AB  - BACKGROUND: Gene transfer efficiency drops significantly when polarized mammary
      epithelial cells are transfected instead of actively growing cells. However,
      fully differentiated cells are the targets for gene transfer in many in vivo
      applications. Therefore, a simple and effective method for the transfection of
      polarized mammary epithelial cells in confluent monolayers was developed.
      METHODS: Reporter gene plasmids were complexed with polyethylenimine with an
      average molecular weight of 25 kDa (PEI 25), or other agents, to transfect
      confluent monolayers of ovine mammary epithelial cells (OMEC II) or human
      carcinoma cells (CaCo-2) in vitro. The improved technique included pretreatment
      of the cells with a hyperosmotic mannitol solution (7%) which caused a loosening
      of the tight contacts between the cells. Alternatively, the mannitol shock could
      be replaced by a short treatment with trypsin or EDTA. In addition to the
      pretreatment, 12.5% polyethyleneglycol with an average molecular weight of 8000
      kDa (PEG 8000) was included in the transfection mixture containing the DNA
      complexes. RESULTS: The combined application of mannitol and PEG resulted in a
      very reliable 5- to 30-fold increase in reporter gene expression in OMEC II and
      CaCo-2 cells, but not K562 cells (an example of another cell type). The improved
      technique can also be combined with other polymer-based transfection agents. The
      transfection rate was enhanced for confluent monolayer cells with fully developed
      epithelial polarity but also for subconfluent, growing epithelial cell cultures.
      CONCLUSIONS: A novel transfection protocol for epithelial cells is presented. The
      combined treatment of cells with mannitol and polyethyleneglycol results in
      substantial enhancement of in vitro transfection of epithelial cell lines.

PMID- 11318111
TI  - Enhanced gene delivery to human airway epithelial cells using an integrin
      targeting lipoplex.
AB  - BACKGROUND: Current liposome-based delivery methods for cystic fibrosis (CF) gene
      therapy are limited by their poor efficiencies. One way to improve this is to use
      a receptor/ligand interaction to increase binding of the transfection complex
      with the target cell. METHODS AND RESULTS: We have tested a synthetic peptide
      containing an alphav integrin-binding motif (arginine-glycine-aspartic acid, RGD)
      and a DNA-binding domain (polylysine) for enhancement of liposome-mediated gene
      delivery. We have shown that integrin proteins capable of binding the RGD motif
      are located on the apical surface of a polarized human bronchial epithelial cell
      line (16HBE). Luciferase gene transfer efficiency to subconfluent 16HBE cells was
      10-200 times higher than gene transfer using either liposome or peptide alone.
      This peptide-mediated enhancement was observed at all cellular contact times
      including those as short as 1 min. Although the transfection efficiency is
      reduced when the 16HBE cells are grown as polarized monolayers, peptide-mediated
      enhancement of lipofection is maintained. Transfection with a lipopolyplex
      containing an RGE (arginine-glucine-glutamic acid) control peptide that cannot
      bind to the alphav integrin molecules, or competitive inhibition with antibodies
      against RGD-binding integrins, reduced gene transfer. Confocal microscopy
      indicated that the peptide increased plasmid delivery to the cell via receptor
      mediated endocytosis. CONCLUSION: These results indicate that integrin-binding
      peptides represent one way to enhance liposome-mediated gene delivery to
      pulmonary epithelia.

PMID- 11318112
TI  - Polyethylenimine-mediated gene delivery: a mechanistic study.
AB  - BACKGROUND: Ethylenimine polymers (PEIs) belong to one of the most efficient
      family of cationic compounds for delivery of plasmid DNA into mammalian cells.
      The high transfection efficiencies are obtained even in the absence of
      endosomolytic agents such as fusogenic peptides or chloroquine, which is in
      contrast to most of the other cationic polymers. It has been hypothesized that
      the efficiency of PEI is due to its capacity to buffer the endosomes. METHODS: To
      investigate the importance of the acidification of endosomes during PEI-mediated
      DNA transfer we used proton pump inhibitors such as bafilomycin A1 and
      concanamycin A. Moreover, we tested whether PEI is able to destabilize natural
      membranes per se at neutral or acidic pH by performing erythrocyte lysis assays.
      RESULTS: PEI-mediated transfection in the presence of bafilomycin A1 resulted in
      a 7-74-fold decrease in reporter gene expression depending on the cell line used.
      In contrast, the efficiency of the monocationic lipid, DOTAP, was not importantly
      altered in the presence of the drug. Furthermore, the present data show that PEI
      cannot destabilize erythrocyte membranes, even at acidic pH, and that PEI,
      complexed or not to DNA, can increase the transfection efficiency of the cationic
      polymer, polylysine, when added at the same time to the cells. CONCLUSIONS: The
      transfection efficiency of PEIs partially relies on their ability to capture the
      protons which are transferred into the endosomes during their acidification. In
      addition, PEI is able to deliver significant amounts of DNA into cells and the
      DNA complexes involved in the expression of the transgene escape within 4 h from
      the endosomes.

PMID- 11318113
TI  - VP22 enhanced intercellular trafficking of HSV thymidine kinase reduced the level
      of ganciclovir needed to cause suicide cell death.
AB  - BACKGROUND: The inefficiency of herpes simplex virus thymidine kinase (TK) gene
      transfer and toxicity of ganciclovir (GCV) at high concentrations in vivo limits
      the use of this suicide gene therapy approach for the treatment of cancers in
      clinical settings. To overcome the problem, we have sought evidence of
      amplification of cytotoxicity by co-transfer of the TK gene fused with the gene
      encoding HSV-1 structural protein VP22 which has a remarkable ability for
      intercellular trafficking. METHODS: The expression of the fusion proteins from
      the chimeric VP22-TK or VP22-EGFP genes was shown by Western blot and VP22
      promoted TK or EGFP intercellular trafficking by an indirect immunofluorescent
      assay. The cytotoxicity was demonstrated by a colorimetric cell proliferation
      assay followed by an assessment of the bystander effect on admixtures of
      transfected with non-transfected naive cells. RESULTS: Our results show the
      expression of the VP22 fusion proteins and their spread to varying numbers of
      bystander cells (up to 30, observed in viable cells with VP22-EGFP as well as
      after methanol fixation), confirming that VP22 assisted intercellular trafficking
      of the fusion proteins. This VP22 promoted TK spreading resulted in killing by
      2.5 microg/ml GCV of virtually all cells in cultures that had been transfected at
      an efficiency of only 27.5%. In contrast, fewer than 80% of cells were killed
      when transfected with 'tk alone' at the same efficiency. The cell killing effect
      was exponentially dependent on GCV concentration in cells transfected with 'tk
      alone' at GCV concentrations between 0.25 and 0.5 microg/ml, but not those
      transfected with VP22-TK, probably due to the continuously variable, high
      sensitivity of about 50% of cells. Even at low concentration of GCV (0.2
      microg/ml), the enhancement of cell killing by VP22 was four-fold higher in cells
      transfected with VP22-TK than in cells transfected with 'tk alone'. CONCLUSIONS:
      VP22 enhanced intercellular trafficking of TK and amplified the TK/GCV killing
      effect, especially in the lower range of GCV concentrations. This offers a new
      strategy to enhance the effectiveness of suicide gene therapy for the treatment
      of cancers.

PMID- 11318114
TI  - Ca2+-sensitive cytosolic nucleases prevent efficient delivery to the nucleus of
      injected plasmids.
AB  - BACKGROUND: Efficient gene delivery by synthetic vectors is a major challenge in
      gene therapy. However, inefficient nuclear delivery of cDNA is thought to be a
      major limiting step in gene transfer using non-viral vectors. It is commonly
      thought that, in the cytosol, cDNA has to be released from its vector before
      importation to the nucleus. The stability of naked cDNA in the cytoplasm is not
      well established. METHODS: cDNA plasmids, either free or complexed with
      poly(ethyleneimine) (PEI), were microinjected into the cytoplasm of mammalian
      cells and their turnover was assessed by fluorescence in situ hybridization
      (FISH). Incubations of cDNA plasmids in cytosolic extracts were also performed.
      RESULTS: FISH experiments showed that naked cDNA rapidly fade with time when
      injected into the cytosol. Fading was not observed when naked cDNA plasmids were
      injected into the nucleus. Incubation of naked cDNA in a cytosolic fraction
      isolated from mammalian cells reproduced cDNA degradation as observed in
      microinjection experiments. Nuclease inhibitors, including aurin tricarboxylic
      acid or Zn2+, prevented in vitro cDNA degradation. The cytosolic nuclease
      activity was optimal at physiological pH and physiological Ca2+ concentration. By
      contrast, it was insensitive to Mg2+ or Na+ concentrations. Finally, cDNA
      complexation with PEI or addition of oligonucleotides prevented in vitro cDNA
      degradation. CONCLUSION: Altogether, these experiments suggest that cDNA
      digestion by cytosolic nucleases occur when the decomplexed transgene is present
      in the cytosol. We propose that the inefficient transfer of cDNA into the nucleus
      during transfection with synthetic vectors may result from rapid digestion of
      naked cDNA by a Ca2+-sensitive cytosolic nuclease.

PMID- 11318115
TI  - A gene therapy/targeted radiotherapy strategy for radiation cell kill by.
AB  - BACKGROUND: Although [131I]meta-iodobenzylguanidine (MIBG) is currently one of
      the best agents available for targeted radiotherapy, its use is confined to a few
      neural crest derived tumours which accumulate the radiopharmaceutical via the
      noradrenaline transporter (NAT). To determine whether this drug could be used for
      the treatment of non-NAT expressing tumours following genetic manipulation, we
      previously showed that plasmid mediated transfection of NAT into a non-NAT
      expressing glioblastoma cell line, UVW, endowed the host cells with the capacity
      to actively accumulate [131I]MIBG. We now present data defining the conditions
      required for complete sterilisation of NAT transfected cells cultured as
      multicellular spheroids and treated with [131I]MIBG. METHODS: NAT transfected UVW
      cells, grown as monolayers and spheroids, were treated with various doses of
      [131I]MIBG and assessed for cell kill by clonogenic survival and measurement of
      spheroid volume over time (growth delay). Spheroids were left intact for
      different time periods to assess the effect of radiation crossfire on cell death.
      RESULTS AND CONCLUSIONS: Total clonogen sterilisation was observed when the cells
      were grown as three-dimensional spheroids and treated with 7 MBq/ml [131I]MIBG.
      The added benefit of radiation crossfire was demonstrated by the improvement in
      cell kill achieved by prolongation of the maintenance of [131I]MIBG treated
      spheroids in their three-dimensional form, before disaggregation and clonogenic
      assay. When left intact for 48 h after treatment, spheroid cure was achieved by
      exposure to 6 MBq/ml [131I]MIBG. These results demonstrate that the efficiency of
      cell kill by [131I]MIBG targeted therapy is strongly dependent on beta-particle
      crossfire irradiation. This gene therapy/targeted radiotherapy strategy has
      potential for [131I]MIBG mediated cell kill in tumours other than those derived
      from the neural crest.

PMID- 11318116
TI  - Optimized in situ PCR method for the detection of gene transfer vector in
      histological sections.
AB  - BACKGROUND: Detection of transferred genes in histological sections has been
      problematic due to low transfection efficiency and copy number achieved with
      current vectors. In situ polymerase chain reaction (in situ PCR) is a new method
      for the detection of low-abundance nucleic acid targets in tissue sections.
      METHODS: We have adapted in situ PCR method for the detection and histological
      localization of transgene DNA after in vivo and ex vivo retroviral gene transfer
      by using mild fixation and permeabilization methods. We used 4%
      paraformaldehyde/15% sucrose fixation combined with proteinase K permeabilization
      and microwave treatment. PCR signal was detected with non-radioactive digoxigenin
      dUTP tailed oligonucleotide sense-probe. RESULTS: The method was applicable for
      both paraffin-embedded and frozen tissue sections and reached the sensitivity to
      detect a few copies of target DNA sequence per cell. CONCLUSIONS: In situ PCR is
      a sensitive method to localize integrated gene transfer vectors and to analyze
      the relationship between expression of the treatment gene and biological effects
      in the transfected tissues.

PMID- 11318117
TI  - Critical assessment of the nuclear import of plasmid during cationic lipid
      mediated gene transfer.
AB  - BACKGROUND: Cationic lipid-mediated gene transfer is a promising approach for
      gene therapy. However, despite the significant amount of lipoplexes internalized
      by target cells, transgene expression remains too low. Obstacles to nuclear
      accumulation of plasmid DNA include: the passage of DNA across the cellular
      membrane, the dismantling of nucleolipidic particles in the cytoplasm and the
      nuclear import of plasmid DNA. The purpose of the present study was to evaluate
      the impact of cell status on cationic lipid-mediated transfer. METHODS: Cells
      were either growth-arrested (by aphidicolin) or synchronized (by a classical
      double-thymidine block protocol) and cationic lipid-mediated transfection of
      these cells was evaluated. For the study of the nuclear import of plasmid DNA,
      two techniques were developed: microinjection of plasmid DNA into intact cells,
      and the use of cells permeabilized with digitonin. RESULTS: When CV-1 cells were
      growth-arrested by aphidicolin, cationic lipid-mediated gene transfer was
      inhibited. Hela cells were synchronized and incubated with lipoplexes at
      different times after release of the block. Gene expression was greatly enhanced
      when cells underwent mitosis. When transfection was performed during the early
      period after block release, when fewer than 5% of the cells had divided, gene
      expression was carefully quantified and could be attributed to cells that escaped
      cell cycle block. However, by direct analysis of nuclear import of GFP-coding
      plasmid using cytoplasmic microinjection, GFP expression could be detected in a
      few cells that had not divided. CONCLUSIONS: Cationic lipid-mediated gene
      transfer efficiency increased when cells underwent mitosis. However, when cells
      did not divide, gene transfer was not completely abolished. Nuclear import of
      plasmid was greatly facilitated by a mitotic event. In non-mitotic cells, nuclear
      envelope crossing by plasmid DNA could be detected but was a very rare event.

PMID- 11318118
TI  - Concentration of viral vectors by co-precipitation with calcium phosphate.
AB  - BACKGROUND: The envelope glycoproteins, surface unit (SU) and transmembrane (TM)
      of the murine leukemia virus (MLV) are not covalently linked and tend to
      dissociate upon high-speed centrifugation, leading to loss of vector infectivity.
      This study describes a gentle and simple method to concentrate MLV vectors or HIV
      vectors pseudotyped with MLV envelopes. Having a fast and inexpensive method to
      concentrate large volumes of vector supernatant will facilitate in vivo
      experiments and clinical trials that require high titer vector stocks. METHODS:
      The methods employed in the study were co-precipitation of viral supernatant with
      calcium phosphate, low-speed centrifugation, dialysis, and infection assays with
      Lac-Z transducing vectors. RESULTS: Murine leukemia virus vectors and HIV vectors
      pseudotyped with vesicular stomatitis virus glycoprotein (VSV.G) or MLV envelopes
      were concentrated successfully using the calcium phosphate co-precipitation
      method. Parameters that influence virus yield and the reproducibility of the
      method were investigated. The optimized protocol involves virus harvest in serum
      free media, co-precipitation using 60mM calcium chloride, pelleting at 2,000 g,
      resuspending the pellet in a small volume of 0.1M EDTA-saline, and dialysis
      against saline to remove EDTA. Volumes were decreased from 300 ml to 10 ml, with
      50-100% recovery, and titers can be concentrated up to 1,000-fold. CONCLUSIONS:
      The calcium phosphate co-precipitation method to concentrate virus is applicable
      to retrovirus and lentivirus preparations. It uses simple techniques and does not
      require expensive equipment. Multiple rounds of co-precipitation can be carried
      out if required.

PMID- 11318119
TI  - Comparison of short-term versus long-term epidural analgesia after limited
      thoracotomy with special reference to pain score, pulmonary function, and
      respiratory muscle strength.
AB  - To determine the optimal duration of epidural analgesia (EA) after lung cancer
      surgery, a retrospective analysis was conducted to compare chest pain, pulmonary
      function, and respiratory muscle strength between patients given EA until
      postoperative day (POD) 3 and those given EA until POD 8. Each group comprised 25
      lung cancer patients who underwent a lobectomy under anterior limited thoracotomy
      and given continuous thoracic EA using morphine until POD 3 (POD3-EA group) or
      POD 8 (POD8-EA group). The two groups were matched by sex and age. Postoperative
      pain from PODs 1 to 12 was evaluated by the pain score and analgesic
      requirements. The pulmonary function and respiratory muscle strength were
      measured on POD 7. The POD3-EA group did not experience any increase in pain
      after withdrawal, but the POD8-EA group did show a significant increase in pain
      the day after withdrawal (P < 0.05). The pain scores on PODs 8 and 9 in the POD8
      EA group were significantly higher than those in the POD3-EA group (P < 0.05).
      There was no significant difference in pulmonary function and respiratory muscle
      strength on POD 7 between the two groups. Although the postoperative thoracic EA
      did not affect pulmonary function and respiratory muscle strength, prolonged
      thoracic EA after a limited thoracotomy significantly increased the pain after
      withdrawal, thus negatively affecting postoperative pain control.

PMID- 11318120
TI  - Lymph node metastasis in cancer of the middle-third stomach: criteria for
      treatment with a pylorus-preserving gastrectomy.
AB  - A retrospective study was conducted to establish the criteria for performing a
      pylorus-preserving gastrectomy. This study was performed on 491 patients who had
      cancer of the middle-third stomach and had been curatively treated with a distal
      gastrectomy. The incidence of node metastasis for each lymph node station (the
      group of regional lymph nodes which have been anatomically defined and classified
      by the Japanese Classification of Gastric Carcinoma) was evaluated with reference
      to the depth of invasion, tumor size, and circumferential location, to show any
      significant correlations with an increase in tumor diameter or in the depth of
      tumor invasion. The benefits of resecting each station was then evaluated based
      on the incidence of metastasis to each station and the rate of long-term
      survivors among those with metastasis to each station. The benefit was
      substantial for the lymph nodes along the lesser curvature, along the right
      gastroepiploic artery, and at the base of the left gastric artery, while the
      advantages were almost negligible for the suprapyloric nodes and right
      paracardial nodes. In conclusion, carcinoma that fulfills either of the following
      conditions may thus be indicated to undergo a pylorus-preserving gastrectomy: (i)
      restricted to a depth of m or sml, (ii) a depth of sm2 or mp with a diameter of
      less than 2cm, (ii) a depth of sm2 or mp and located in the greater curvature.

PMID- 11318121
TI  - Surgical treatment and subsequent outcome of patients with carcinoma of the
      splenic flexure.
AB  - Extended resection, comprising extended right hemicolectomy, splenectomy, and
      distal pancreatectomy, has been advocated for carcinoma of the splenic flexure
      because the lymphatic drainage at this site is variable. The present study
      addresses the problems associated with selecting the most appropriate operative
      procedure to achieve cure of splenic flexure cancers. We conducted a
      retrospective review of 27 patients with splenic flexure cancer who underwent
      curative resection. Left partial colectomy was performed in 20 patients and
      partial resection of the transverse/descending colon was performed in 7 patients.
      The combined resection of adjacent organs due to tumor adherence was performed in
      three patients. The spleen and distal pancreas were the organs most frequently
      resected among a collective total of six adjacent organs. The median duration of
      follow-up was 60.9 months after resection for splenic flexure cancer. No patient
      developed local recurrence. There was no significant difference in 5-year
      survival between patients with splenic flexure cancers and those with colon
      cancers at other sites. In conclusion, splenic flexure cancer resected by left
      partial colectomy or partial resection of the transverse/descending colon without
      routine extended resection was not associated with a worse prognosis than colon
      cancers at other sites.

PMID- 11318122
TI  - Laparascope-assisted versus conventional restorative proctocolectomy with rectal
      mucosectomy.
AB  - To assess the advantages of a laparoscope-assisted proctocolectomy with ileal J
      pouch anal anastomosis compared with conventional procedures, we retrospectively
      analyzed the results of the two procedures as follows: Eleven patients including
      five patients with familial adenomatous polyposis (FAP) and six with ulcerative
      colitis (UC) underwent a laparoscope-assisted proctocolectomy and hand-sewn ileal
      J-pouch anal anastomosis at our department from June 1997 to November 1999. This
      laparoscope-assisted colectomy (LAC) group was then compared with a group of 13
      patients who had undergone conventional ileal pouch anal anastomosis using a
      standard laparotomy from 1986 to 1997. The median operative time of the LAC group
      was 8h 23min, which was 81 min longer than that of the standard colectomy (SC)
      group. The number of days during which eating was prohibited were similar in the
      two groups but the median postoperative hospital stay was significantly shorter
      in the LAC group (24.1 days). In the LAC group, the small incisions showed better
      cosmetic results and there was also a remarkable reduction in the degree of
      postoperative pain. In conclusion, a laparoscope-assisted proctocolectomy with
      ileal J-pouch anal anastomosis can be employed widely in patients with FAP and
      also in selected patients with UC.

PMID- 11318123
TI  - The impact of various suture materials on experimental colorectal carcinogenesis.
AB  - Local tumor recurrence following restorative surgery for colorectal cancer may
      occasionally result from the promotion of a neoplastic lesion in a zone of
      proliferative instability adjacent to the anastomosis. This study was designed to
      determine the influence of various suture materials on experimental colorectal
      carcinogenesis. A total of 72 rats were divided into six groups, four of which
      were subjected to colotomy and repair using catgut, silk, polyglactin (PG), or
      stainless steel. The fifth group was given a sham procedure and the sixth group
      served as a control. Methylnitrosourea was administered rectally to all the
      animals, at a dose of 4 mg/kg/week for 20 weeks. The mean number of tumors per
      rat was significantly higher in the PG group than in the other groups. The mean
      tumor size was found to be significantly larger in each of the suture material
      groups than in the sham group. A tendency for tumor occurrence to develop at the
      anastomosis rather than at the other colon sites was seen in the PG group. These
      results indicate that PG has an adverse effect on local tumor occurrence in
      experimental colorectal carcinogenesis.

PMID- 11318124
TI  - Spontaneous rupture of a parathyroid adenoma presenting as a massive cervical
      hemorrhage: report of a case.
AB  - We report an unusual case of spontaneous rupture of a parathyroid adenoma causing
      cervical hemorrhage. A 60-year-old woman presented to our hospital after the
      sudden development of extensive ecchymosis of her neck and upper anterior chest
      wall. Computed tomography (CT) scanning revealed a hematoma in the left
      retrotracheal space, and laboratory examinations revealed significant
      hypercalcemia, hypophosphatemia, and a high level of intact parathyroid hormone.
      Primary hyperparathyroidism was diagnosed, but it was not until the hematoma had
      subsided, 4 months after her initial presentation, that a parathyroid adenoma was
      revealed by CT. An operation was performed, and a parathyroid adenoma with
      hemosiderin deposition was histologically diagnosed. Although this phenomenon is
      unusual, all endocrine surgeons should be well aware of the possibility of its
      occurrence.

PMID- 11318125
TI  - Solitary thyroid metastasis of renal clear cell carcinoma: report of a case.
AB  - A case of solitary thyroid metastasis of renal clear cell carcinoma is described.
      The patient was a 77-year-old Japanese woman, who was referred to our department
      after a thyroid tumor was identified in May 1999. She had a history of renal
      clear cell carcinoma of the left kidney, which had been partially resected 3
      years previously. Ultrasound sonography demonstrated that a well-demarcated
      hypoechoic mass containing high-echo spots representing small calcifications,
      which measured 45 x 34 x 31 mm in size, occupied the left lobe. Computed
      tomography revealed a low-density mass containing small calcifications. The
      results of preoperative fine-needle aspiration cytology strongly suggested a
      clear cell carcinoma metastasizing to the thyroid. A left hemithyroidectomy was
      performed on July 27, 1999. A histological examination revealed that the neoplasm
      was composed of tumor cells with abundant clear cytoplasm and round nuclei. The
      histological characteristics of this thyroid tumor were virtually identical to
      the renal cell carcinoma resected 3 years previously. Thyroglobulin stained
      negatively in the clear cells of the resected thyroid tumor in an
      immunohistochemical analysis. Clinically, the thyroid gland is a rare site of
      tumor metastasis; however, we should also consider the possibility of metastasis
      in the case of thyroid tumor patients with a history of renal cell carcinoma.

PMID- 11318126
TI  - Successful resection of a primary liposarcoma in the anterior mediastinum in a
      child: report of a case.
AB  - Primary liposarcomas of the mediastinum are very rare. We report on a 13-year-old
      girl who presented with a huge mediastinal tumor. The tumor was extirpated by a
      median sternotomy with a right thoracotomy. The tumor included the superior vena
      cava in the anterior mediastinum. It therefore probably originated from the
      anterior mediastinal fat tissue, possibly from the thymus. A pathological
      examination revealed myxoid liposarcoma. At 35 months postoperatively, the
      patient has not shown any recurrence.

PMID- 11318127
TI  - Adult T-cell leukemia associated with gastric carcinoma: report of a case.
AB  - A 67-year-old man was admitted to our hospital with nausea and epigastralgia, and
      a diagnosis of smoldering type adult T-cell leukemia (ATL) associated with
      advanced gastric carcinoma was made. The gastric carcinoma had caused pyloric
      stenosis, and investigations revealed regional lymph node metastasis. The patient
      underwent total gastrectomy, splenectomy, cholecystectomy, and lymph node
      dissection with a Roux-en-Y anastomosis. Histological examination of the regional
      lymph nodes revealed not only metastases of gastric carcinoma, but also of ATL
      lymphoma, indicating a final diagnosis of advanced gastric carcinoma with
      locoregional lymph node due to both metastasis of the gastric carcinoma and the
      ATL lymphoma. Despite the administration of postoperative adjuvant chemotherapy
      comprised of cisplatin/adriamycin/5-fluorouracil in combination with oral
      etoposide and immunotherapy using ubenimex, paraplegia suddenly developed caused
      by the metastasis of ATL to the epidural space. Resection of this metastatic
      tumor for decompression of the spinal cord resulted in resolution of the
      paraplegia; however, the patient died about 1 month later from rapid systemic
      tumor growth.

PMID- 11318128
TI  - Extended surgery with en bloc resection of the right common iliac vessels for
      lymph node metastasis of mucinous colon carcinoma: report of a case.
AB  - We report herein the case of a 63-year-old woman who underwent surgery for
      recurrent mucinous carcinoma of the cecum. Recurrent metastatic lymph nodes had
      invaded the right common iliac vessels and right ureter, but she had no distant
      metastases and no peritoneal dissemination. Extended surgery with en bloc
      resection of the right iliac vessels and right ureter, and femorofemoral bypass
      were performed. Postoperatively, several complications developed which were
      successfully treated by further operations. By 1 year after surgery, she had no
      recurrent tumors on radiological examination, suggesting that our aggressive
      surgery with resection of the invaded regional vessels had effectively removed
      the recurrent tumors. This procedure may therefore significantly prolong the
      survival time and improve the quality of life of such patients.

PMID- 11318129
TI  - Malignant fibrous histiocytoma of the ileum at a site of previous surgery: report
      of a case.
AB  - Sarcomas rarely arise in the intestinum, and leiomyosarcoma represents the
      majority of cases. With only seven cases reported in the available English
      literature up to now, malignant fibrous histiocytoma of the small intestine is
      exceedingly rare. Moreover, follow-up data are almost completely unavailable. We
      present herein the unique case of a malignant fibrous histiocytoma arising in a
      postoperatively adherent intestinal loop. To the best of our knowledge, this is
      the first such case ever to be described. The clinical history and the
      intraoperative findings suggested that chronic postoperative repair processes
      might have been a promoting factor in the tumorigenesis of this neoplasm, on the
      analogy of malignant fibrous histiocytoma arising at different sites. The patient
      recovered well but 9.5 years after surgical removal, a solitary recurrent tumor
      developed in the urinary bladder and progressed rapidly, highlighting the need
      for long-term, possibly life-long, surveillance of patients with this rare type
      of intestinal cancer.

PMID- 11318130
TI  - Pneumatosis intestinalis in the small bowel of an adult: report of a case.
AB  - We present the case of a 70-year-old man found to have pneumatosis of the small
      intestine. An abdominal computed tomography (CT) scan detected massive intramural
      air in the entire circumference of the small intestine without any venous gas.
      During emergency surgery, 80 cm of the small bowel was removed. The pathological
      findings of thrombi in the resected specimen thus indicated that surgical
      intervention should be immediately performed in patients with pneumatosis
      throughout the small intestine. CT was useful for confirming the presence of
      intramural gas in pneumatosis of the small intestine. The presence of a massive
      amount of intramural gas in the entire small intestine circumference on the CT
      findings is thus considered to be an early indication of bowel infarction.

PMID- 11318131
TI  - Pneumoperitoneum: an absolute indication for surgery in infants with necrotizing
      enterocolitis?: Report of a case.
AB  - It is generally agreed that neonates with necrotizing enterocolitis (NEC) and
      pneumoperitoneum should be treated surgically. We report herein the case of a 3
      day-old male newborn with NEC in whom a pneumoperitoneum subsequently developed
      without any cause found at laparotomy. This case is presented to discuss the
      nonsurgical management of pneumoperitoneum in selected patients.

PMID- 11318132
TI  - Multifocal carcinoid tumor resembling a solitary tumor: report of a case.
AB  - A laparotomy was performed on a 44-year-old male patient with an acute abdomen
      who had findings suggestive of acute appendicitis and a periappendicular abscess.
      A histopathological examination revealed a carcinoid tumor infiltrating the
      intestinal serosa. The distal ileum and cecum were infiltrated with more than 40
      multifocal tumors, with the largest measuring 1 cm in size. The distal ileum and
      cecum were resected. We failed to find any distant metastases either
      peroperatively or during postoperative scintigraphic tests. In addition, the
      patient had no symptoms of carcinoid syndrome either before or after surgery. No
      recurrence was experienced. We thus conclude that primary multifocal carcinoid
      tumors may act as a solitary carcinoid tumor, and the largest tumor tends to
      indicate the overall clinical outcome.

PMID- 11318133
TI  - Colovesical fistula due to a lost gallstone following laparoscopic
      cholecystectomy: report of a case.
AB  - We report the case of a 74-year-old man with a colovesical fistula caused by a
      gallstone that was lost during a laparoscopic cholecystectomy 7 months earlier.
      The patient was cured after undergoing colonoscopic removal of the stone. To our
      knowledge this is the first case report of such a complication in the English
      literature. The report reviews the outcome and complications of retained
      intraperitoneal gallstones.

PMID- 11318134
TI  - Laparoscopic splenectomy for a lymphangioma of the spleen: report of a case.
AB  - We present the first case report of a successful laparoscopic complete excision
      of a splenic lymphangioma. The splenic tumor was preoperatively diagnosed to be a
      lymphangioma by the combined modalities of ultrasonography, computed tomography,
      magnetic resonance imaging, and angiography. A laparoscopic splenectomy was
      subsequently performed and the pathological examination of the mass confirmed the
      diagnosis of a lymphangioma. Based on the above findings, a laparoscopic
      splenectomy is recommended when a splenic tumor is suspected to be either benign
      or borderline.

PMID- 11318135
TI  - Posttraumatic splenic cysts and partial splenectomy: report of a case.
AB  - Nonparasitic splenic cysts are uncommon, with only around 800 cases described in
      the literature. Posttraumatic splenic pseudocysts constitute most such cases and
      require surgical treatment when symptomatic or voluminous. Recent studies have
      provided a better understanding of splenic tissue function and the consequent
      risks of complete resection of the spleen. Hence surgeons should make every
      possible effort to preserve splenic tissue. Several spleen-conserving surgical
      treatments have been proposed, especially for treatment of splenic posttraumatic
      pseudocysts. The authors report the case of a 13-year-old girl who had a
      posttraumatic splenic cyst with progressive growth. The diameter of the cyst at
      surgery was 15 cm, and partial splenectomy was performed. The most common spleen
      conserving surgical techniques are briefly reviewed.

PMID- 11318136
TI  - Renal pelvic carcinoma producing granulocyte colony-stimulating factor: report of
      a case.
AB  - A 69-year-old man was admitted to our hospital because of anorexia and weight
      loss. Abdominal computed tomography showed an irregularly contoured mass in his
      left renal pelvis. The patient had a remarkable degree of leukocytosis with no
      obvious focus of infection. An enzyme immunoassay of the serum revealed a
      remarkably high concentration of granulocyte colony-stimulating factor (G-CSF).
      The patient died 6 weeks after admission without a resection of the renal pelvic
      tumor. At autopsy, the tumor involved the pancreas, stomach, and descending
      colon. The histopathologic diagnosis was squamous cell carcinoma with sarcomatous
      change. Immunohistochemical staining using anti-G-CSF antibody demonstrated
      immunoreactivity in the cancer cells. To our knowledge, this is the first case of
      renal pelvic carcinoma proven to produce G-CSF reported in English.

PMID- 11318137
TI  - Fatal diffuse atheromatous embolization following endovascular grafting for an
      abdominal aortic aneurysm: report of a case.
AB  - A 78-year-old woman with an abdominal aortic aneurysm, 57 mm in diameter, was
      admitted to our hospital for endovascular grafting. Preoperative computed
      tomography and angiography showed friable mural thrombus in the suprarenal and
      infrarenal aorta, and a diagnosis of shaggy aorta was made. Postoperatively, the
      patient suffered cerebral infarction, and disseminated intravascular coagulopathy
      with multiple organ failure developed, resulting in early death on the third day
      after surgery. An autopsy revealed diffuse atheromatous embolization into the
      celiac, superior mesenteric, bilateral renal, bilateral hypogastric (trash
      buttock), and peripheral arteries. This case report serves to demonstrate that an
      abdominal aortic aneurysm with a shaggy aorta in the proximal neck is a
      contraindication to endovascular grafting, and that predicting the possibility of
      diffuse atheromatous embolization by detecting a shaggy aorta is the best way to
      prevent this catastrophic complication.

PMID- 11318138
TI  - Direct hypogastric artery reconstruction for threatened lower limb ischemia:
      report of a case.
AB  - The hypogastric artery is one of the major collateral arteries in aortoiliac
      occlusive disease. This report describes a case of limb-threatening ischemia
      caused by acute arterial thrombosis of the right hypogastric artery. The external
      iliac and distal arteries were obstructed and the hypogastric artery was a major
      collateral artery. A diagnostic arteriogram taken after intra-arterial
      thrombolytic therapy revealed a stenotic lesion in the orifice of the hypogastric
      artery. Open thromboendarterectomy of the hypogastric artery and patch
      angioplasty, using an expanded polytetrafluoroethylene graft, were performed to
      salvage the limb. The hypogastric artery was successfully revascularized and
      ischemic rest pain was relieved.

PMID- 11318139
TI  - "Growth factor" technique using expanded polytetrafluoroethylene monofilament for
      arteriovenous fistulae.
AB  - We employed the "growth factor" technique first described by Starzl et al. to
      construct 12 consecutive end-to-end arteriovenous wrist fistulas (AVWF) for
      chronic hemodialysis, using expanded polytetrafluoroethylene (ePTFE) monofilament
      (Gore-Tex) as the suture material. A complete migration of the "growth factor"
      loop through the vessel walls was observed and immediate patency of the AVWF was
      achieved in all patients. Although AVWF thrombosis developed in one patient, no
      other complications were observed in the early postoperative period. The 2-month
      AVWF patency rate was 90.9%. The ePTFE sutures demonstrated an adequate sliding
      property which make this monofilament a satisfactory material for vascular
      anastomosis constructed using this technique.

PMID- 11318140
TI  - Surgical management of a graftenteric fistula: a modified method of in situ
      reconstruction.
AB  - Between December 1989 and May 1998, we performed a modified method of in situ
      reconstruction on three of seven patients with graftenteric fistulas (GEFs) at
      the Kurume University Hospital. The modification involved performing an
      anastomosis of the infrarenal abdominal aorta and running a new prosthesis
      through the left side of the descending colon in the retroperitoneal cavity, and
      wrapping the proximal anastomosis and the proximal site of the prosthesis in the
      greater omentum. Good results were achieved in all three patients. We describe
      herein this modified method of in situ reconstruction for a GEF and summarize the
      case reports of these three patients.

PMID- 11318141
TI  - Balloon catheter for cyst aspiration in a thoracoscopic resection of mediastinal
      cysts.
AB  - In a thoracoscopic resection of mediastinal cysts, aspiration of the cyst
      contents at the beginning of the procedure is often helpful because it allows the
      cyst to be more easily grasped and manipulated. Spillage of the cyst contents
      into the thoracic cavity may, however, occur during aspiration when an ordinary
      aspiration needle is used. If the cyst contents are infective, then a subsequent
      contamination of the thoracic cavity may develop. We therefore use a specially
      designed double-balloon catheter for aspiration to minimize spillage of the cyst
      contents into the thoracic cavity. We describe herein the usefulness of this
      aspiration technique.

PMID- 11318142
TI  - Bayesian phylogenetic inference via Markov chain Monte Carlo methods.
AB  - We derive a Markov chain to sample from the posterior distribution for a
      phylogenetic tree given sequence information from the corresponding set of
      organisms, a stochastic model for these data, and a prior distribution on the
      space of trees. A transformation of the tree into a canonical cophenetic matrix
      form suggests a simple and effective proposal distribution for selecting
      candidate trees close to the current tree in the chain. We illustrate the
      algorithm with restriction site data on 9 plant species, then extend to DNA
      sequences from 32 species of fish. The algorithm mixes well in both examples from
      random starting trees, generating reproducible estimates and credible sets for
      the path of evolution.

PMID- 11318143
TI  - An estimation method for the semiparametric mixed effects model.
AB  - A semiparametric mixed effects regression model is proposed for the analysis of
      clustered or longitudinal data with continuous, ordinal, or binary outcome. The
      common assumption of Gaussian random effects is relaxed by using a predictive
      recursion method (Newton and Zhang, 1999) to provide a nonparametric smooth
      density estimate. A new strategy is introduced to accelerate the algorithm.
      Parameter estimates are obtained by maximizing the marginal profile likelihood by
      Powell's conjugate direction search method. Monte Carlo results are presented to
      show that the method can improve the mean squared error of the fixed effects
      estimators when the random effects distribution is not Gaussian. The usefulness
      of visualizing the random effects density itself is illustrated in the analysis
      of data from the Wisconsin Sleep Survey. The proposed estimation procedure is
      computationally feasible for quite large data sets.

PMID- 11318144
TI  - Bias-corrected confidence intervals for the concentration parameter in a dilution
      assay.
AB  - Interval estimates of the concentration of target entities from a serial dilution
      assay are usually based on the maximum likelihood estimator. The distribution of
      the maximum likelihood estimator is skewed to the right and is positively biased.
      This bias results in interval estimates that either provide inadequate coverage
      relative to the nominal level or yield excessively long intervals. Confidence
      intervals based on both log transformation and bias reduction are proposed and
      are shown through simulations to provide appropriate coverage with shorter widths
      than the commonly used intervals in a variety of designs. An application to
      feline AIDS research, which motivated this work, is also presented.

PMID- 11318145
TI  - A general maximum likelihood analysis of variance components in generalized
      linear models.
AB  - This paper describes an EM algorithm for nonparametric maximum likelihood (ML)
      estimation in generalized linear models with variance component structure. The
      algorithm provides an alternative analysis to approximate MQL and PQL analyses
      (McGilchrist and Aisbett, 1991, Biometrical Journal 33, 131-141; Breslow and
      Clayton, 1993; Journal of the American Statistical Association 88, 9-25;
      McGilchrist, 1994, Journal of the Royal Statistical Society, Series B 56, 61-69;
      Goldstein, 1995, Multilevel Statistical Models) and to GEE analyses (Liang and
      Zeger, 1986, Biometrika 73, 13-22). The algorithm, first given by Hinde and Wood
      (1987, in Longitudinal Data Analysis, 110-126), is a generalization of that for
      random effect models for overdispersion in generalized linear models, described
      in Aitkin (1996, Statistics and Computing 6, 251-262). The algorithm is initially
      derived as a form of Gaussian quadrature assuming a normal mixing distribution,
      but with only slight variation it can be used for a completely unknown mixing
      distribution, giving a straightforward method for the fully nonparametric ML
      estimation of this distribution. This is of value because the ML estimates of the
      GLM parameters can be sensitive to the specification of a parametric form for the
      mixing distribution. The nonparametric analysis can be extended straightforwardly
      to general random parameter models, with full NPML estimation of the joint
      distribution of the random parameters. This can produce substantial computational
      saving compared with full numerical integration over a specified parametric
      distribution for the random parameters. A simple method is described for
      obtaining correct standard errors for parameter estimates when using the EM
      algorithm. Several examples are discussed involving simple variance component and
      longitudinal models, and small-area estimation.

PMID- 11318146
TI  - Maximum likelihood analysis for heteroscedastic one-way random effects ANOVA in
      interlaboratory studies.
AB  - This article presents results for the maximum likelihood analysis of several
      groups of measurements made on the same quantity. Following Cochran (1937,
      Journal of the Royal Statistical Society 4(Supple), 102-118; 1954, Biometrics 10,
      101-129; 1980, in Proceedings of the 25th Conference on the Design of Experiments
      in Army Research, Development and Testing, 21-33) and others, this problem is
      formulated as a one-way unbalanced random-effects ANOVA with unequal within-group
      variances. A reparametrization of the likelihood leads to simplified
      computations, easier identification and interpretation of multimodality of the
      likelihood, and (through a non-informative-prior Bayesian approach) approximate
      confidence regions for the mean and between-group variance.

PMID- 11318147
TI  - Fundamentals of survival data.
AB  - Survival data stand out as a special statistical field. This paper tries to
      describe what survival data is and what makes it so special. Survival data
      concern times to some events. A key point is the successive observation of time,
      which on the one hand leads to some times not being observed so that all that is
      known is that they exceed some given times (censoring), and on the other hand
      implies that predictions regarding the future course should be conditional on the
      present status (truncation). In the simplest case, this condition is that the
      individual is alive. The successive conditioning makes the hazard function, which
      describes the probability of an event happening during a short interval given
      that the individual is alive today (or more generally able to experience the
      event), the most relevant concept. Standard distributions available (normal, log
      normal, gamma, inverse Gaussian, and so forth) can account for censoring and
      truncation, but this is cumbersome. Besides, they fit badly because they are
      either symmetric or right skewed, but survival time distributions can easily be
      left-skewed positive variables. A few distributions satisfying these requirements
      are available, but often nonparametric methods are preferable as they account
      better conceptually for truncation and censoring and give a better fit. Finally,
      we compare the proportional hazards regression models with accelerated failure
      time models.

PMID- 11318148
TI  - Estimating intraclass correlation for binary data.
AB  - This paper reviews many different estimators of intraclass correlation that have
      been proposed for binary data and compares them in an extensive simulation study.
      Some of the estimators are very specific, while others result from general
      methods such as pseudo-likelihood and extended quasi-likelihood estimation. The
      simulation study identifies several useful estimators, one of which does not seem
      to have been considered previously for binary data. Estimators based on extended
      quasi-likelihood are found to have a substantial bias in some circumstances.

PMID- 11318149
TI  - Response surfaces for overdispersion in the study of the conditions for fish eggs
      hatching.
AB  - Response surface methodology, originally developed for determining optimal
      conditions in industrial experiments, was early adapted to experiments in marine
      ecology. However, these involved studying the shape of the complete response
      surface, not only detecting the optimum, and often had counts or durations as the
      response variable. Thus, nonlinear, nonnormal response models were required. For
      counts, binomial and beta-binomial models have been used, the latter because of
      substantial overdispersion. In closely controlled experiments, overdispersion
      among units held under the same conditions might indicate that some mishap has
      occurred in conducting the study. One possible check is to model the dispersion
      as a second response surface. This procedure is used to show that overdispersion
      in fish egg hatching experiments has a biological explanation in that it occurs
      only under suboptimal hatching conditions.

PMID- 11318150
TI  - Comparing the performances of Diggle's tests of spatial randomness for small
      samples with and without edge-effect correction: application to ecological data.
AB  - Diggle's tests of spatial randomness based on empirical distributions of
      interpoint distances can be performed with and without edge-effect correction. We
      present here numerical results illustrating that tests without the edge-effect
      correction proposed by Diggle (1979, Biometrics 35, 87-101) have a higher power
      for small sample sizes than those with correction. Ignoring the correction
      enables detection of departure from spatial randomness with smaller samples (down
      to 10 points vs. 30 points for the tests with correction). These results are
      confirmed by an example with ecological data consisting of maps of two species of
      trees in a West African savanna. Tree numbers per species per map were often less
      than 20. For one of the species, for which maps strongly suggest an aggregated
      pattern, tests without edge-effect correction enabled rejection of the null
      hypothesis on three plots out of five vs. on only one for the tests with
      correction.

PMID- 11318151
TI  - A partial ranking method for identifying repeated inclusion of individuals in
      anonymized HIV infection reports.
AB  - Diagnoses of HIV infection are reported to the Public Health Laboratory Service
      (PHLS) AIDS Centre under a voluntary surveillance scheme. Names are not held in
      the data set, but the date of birth of the individual concerned is usually
      available. This paper describes a statistical method for identifying whether
      there are likely to be individuals repeatedly represented in the resulting data
      set, which is considered by birth year. A partial ordering method is used that is
      especially useful for years where the number of birth years in the sample is too
      small for chi2 tests to be used. At the 5% level, one of the five birth years
      tested in the data supplied to us by the PHLS shows evidence of more replication
      than would be expected from independent random sampling from the population. The
      results are compared with an alternative maximum-likelihood-based test that
      reaches the same conclusions. Maximum likelihood methods are further used to
      estimate the percentage of overcounting of individuals in the sample at 2.7%.

PMID- 11318152
TI  - Discriminant analysis of event-related potential curves using smoothed principal
      components.
AB  - Principal component analysis enhanced by the use of smoothing is used in
      conjunction with discriminant analysis techniques to devise a statistical
      classification method for the analysis of event-related potential data. A
      training set of premedication potentials collected from adolescents with
      attention-deficit hyperactive disorder (ADHD) is used to predict whether
      adolescents from an independent subject group will respond to long-term
      medication. Comparison of outcome prediction rates demonstrates that this method,
      which uses information from the whole ERP curve, is superior to the
      classification technique currently used by clinicians, which is based on a single
      ERP curve feature. The need to administer an initial dose of medication to
      classify patients is also eliminated.

PMID- 11318153
TI  - A random effects model for multivariate failure time data from multicenter
      clinical trials.
AB  - A random effects model for analyzing multivariate failure time data is proposed.
      The work is motivated by the need for assessing the mean treatment effect in a
      multicenter clinical trial study, assuming that the centers are a random sample
      from an underlying population. An estimating equation for the mean hazard ratio
      parameter is proposed. The proposed estimator is shown to be consistent and
      asymptotically normally distributed. A variance estimator, based on large sample
      theory, is proposed. Simulation results indicate that the proposed estimator
      performs well in finite samples. The proposed variance estimator effectively
      corrects the bias of the naive variance estimator, which assumes independence of
      individuals within a group. The methodology is illustrated with a clinical trial
      data set from the Studies of Left Ventricular Dysfunction. This shows that the
      variability of the treatment effect is higher than found by means of simpler
      models.

PMID- 11318154
TI  - Statistical inference for self-designing clinical trials with a one-sided
      hypothesis.
AB  - In the process of monitoring clinical trials, it seems appealing to use the
      interim findings to determine whether the sample size originally planned will
      provide adequate power when the alternative hypothesis is true, and to adjust the
      sample size if necessary. In the present paper, we propose a flexible sequential
      monitoring method following the work of Fisher (1998), in which the maximum
      sample size does not have to be specified in advance. The final test statistic is
      constructed based on a weighted average of the sequentially collected data, where
      the weight function at each stage is determined by the observed data prior to
      that stage. Such a weight function is used to maintain the integrity of the
      variance of the final test statistic so that the overall type I error rate is
      preserved. Moreover, the weight function plays an implicit role in termination of
      a trial when a treatment difference exists. Finally, the design allows the trial
      to be stopped early when the efficacy result is sufficiently negative. Simulation
      studies confirm the performance of the method.

PMID- 11318155
TI  - Survival and hazard functions for progressive diseases using saddlepoint
      approximations.
AB  - Saddlepoint approximations for the computation of survival and hazard functions
      are introduced in the context of parametric survival analysis. Although these
      approximations are computationally fast, accurate, and relatively straightforward
      to implement, their use in survival analysis has been lacking. We approximate
      survival functions using the Lugannani and Rice saddlepoint approximation to the
      distribution function or by numerically integrating the saddlepoint density
      approximation. The hazard function is approximated using the saddlepoint density
      and distribution functions. The approximations are especially useful for
      consideration of survival and hazard functions for waiting times in complicated
      models. Examples include total or partial waiting times for a disease that
      progresses through various stages (convolutions of distributions).

PMID- 11318156
TI  - Adaptive regression splines in the Cox model.
AB  - We develop a method for constructing adaptive regression spline models for the
      exploration of survival data. The method combines Cox's (1972, Journal of the
      Royal Statistical Society, Series B 34, 187-200) regression model with a weighted
      least-squares version of the multivariate adaptive regressi on spline (MARS)
      technique of Friedman (1991, Annals of Statistics 19, 1-141) to adaptively select
      the knots and covariates. The new technique can automatically fit models with
      terms that represent nonlinear effects and interactions among covariates.
      Applications based on simulated data and data from a clinical trial for myeloma
      are presented. Results from the myeloma application identified several important
      prognostic variables, including a possible nonmonotone relationship with survival
      in one laboratory variable. Results are compared to those from the adaptive
      hazard regression (HARE) method of Kooperberg, Stone, and Truong (1995, Journal
      of the American Statistical Association 90, 78-94).

PMID- 11318157
TI  - Likelihood methods for incomplete longitudinal binary responses with incomplete
      categorical covariates.
AB  - We consider longitudinal studies in which the outcome observed over time is
      binary and the covariates of interest are categorical. With no missing responses
      or covariates, one specifies a multinomial model for the responses given the
      covariates and uses maximum likelihood to estimate the parameters. Unfortunately,
      incomplete data in the responses and covariates are a common occurrence in
      longitudinal studies. Here we assume the missing data are missing at random
      (Rubin, 1976, Biometrika 63, 581-592). Since all of the missing data (responses
      and covariates) are categorical, a useful technique for obtaining maximum
      likelihood parameter estimates is the EM algorithm by the method of weights
      proposed in Ibrahim (1990, Journal of the American Statistical Association 85,
      765-769). In using the EM algorithm with missing responses and covariates, one
      specifies the joint distribution of the responses and covariates. Here we
      consider the parameters of the covariate distribution as a nuisance. In data sets
      where the percentage of missing data is high, the estimates of the nuisance
      parameters can lead to highly unstable estimates of the parameters of interest.
      We propose a conditional model for the covariate distribution that has several
      modeling advantages for the EM algorithm and provides a reduction in the number
      of nuisance parameters, thus providing more stable estimates in finite samples.

PMID- 11318158
TI  - Estimating the size of a transient population.
AB  - Migratory populations often stop over for short periods of time at predictable
      sites along their migration routes. These staging areas can be heavily used and
      are potentially critical to the survival of the migrants. This paper presents a
      method for estimating the number of individuals using such an area and their
      average residence time. The estimator is based on daily population estimates and
      records of repeat sightings of identifiable individuals. Its application is
      illustrated with observations on a population of migrating birds, some of which
      could be identified from bands that were readable from a distance.

PMID- 11318159
TI  - The graft versus leukemia effect after bone marrow transplantation: a case study
      using structural nested failure time models.
AB  - Over the last decade, J. M. Robins has developed a set of tools for assessing,
      from observational data, the causal effects of a time-dependent treatment or
      exposure in the presence of time-dependent covariates that may be simultaneously
      confounders and intermediate variables. This report concerns a case study of the
      application of one these techniques, G-estimation using structural nested failure
      time models, to the problem of assessing the effect of graft versus host disease
      on leukemia relapse after bone marrow transplantation.

PMID- 11318160
TI  - Robustness of group testing in the estimation of proportions.
AB  - In binomial group testing, unlike one-at-a-time testing, the test unit consists
      of a group of individuals, and each group is declared to be defective or
      nondefective. A defective group is one that is presumed to include one or more
      defective (e.g., infected, positive) individuals and a nondefective group to
      contain only nondefective individuals. The usual binomial model considers the
      individuals being grouped as independent and identically distributed Bernoulli
      random variables. Under the binomial model and presuming that groups are tested
      and classified without error, it has been shown that, when the proportion of
      defective individuals is low, group testing is often preferable to individual
      testing for identifying infected individuals and for estimating proportions of
      defectives. We discuss the robustness of group testing for estimating proportions
      when the underlying assumptions of (i) no testing errors and (ii) independent
      individuals are violated. To evaluate the effect of these model violations, two
      dilution-effect models and a serial correlation model are considered. Group
      testing proved to be quite robust to serial correlation. In the presence of a
      dilution effect, smaller group sizes should be used, but most of the benefits of
      group testing can still be realized.

PMID- 11318161
TI  - Local EM estimation of the hazard function for interval-censored data.
AB  - We propose a smooth hazard estimator for interval-censored survival data using
      the method of local likelihood. The model is fit using a local EM algorithm. The
      estimator is more descriptive than traditional empirical estimates in regions of
      concentrated information and takes on a parametric flavor in regions of sparse
      information. We derive two different standard error estimates for the smooth
      curve, one based on asymptotic theory and the other on the bootstrap. We
      illustrate the local EM method for times to breast cosmesis deterioration
      (Finkelstein, 1986, Biometrics 42, 845-854) and for times to HIV-1 infection for
      individuals with hemophilia (Kroner et al., 1994, Journal of AIDS 7, 279-286).
      Our hazard estimates for each of these data sets show interesting structures that
      would not be found using a standard parametric hazard model or empirical
      survivorship estimates.

PMID- 11318162
TI  - Approximate Monte Carlo conditional inference in exponential families.
AB  - This article presents an algorithm for approximate frequentist conditional
      inference on two or more parameters for any regression model in the Generalized
      Linear Model (GLIM) family. We thereby extend highly accurate inference beyond
      the cases of logistic regression and contingency tables implimented in
      commercially available software. The method makes use of the double saddlepoint
      approximations of Skovgaard (1987, Journal of Applied Probability 24, 875-887)
      and Jensen (1992, Biometrika 79, 693-703) to the conditional cumulative
      distribution function of a sufficient statistic given the remaining sufficient
      statistics. This approximation is then used in conjunction with noniterative
      Monte Carlo methods to generate a sample from a distribution that approximates
      the joint distribution of the sufficient statistics associated with the
      parameters of interest conditional on the observed values of the sufficient
      statistics associated with the nuisance parameters. This algorithm is an
      alternate approach to that presented by Kolassa and Tanner (1994, Journal of the
      American Statistical Association 89, 697-702), in which a Markov chain is
      generated whose equilibrium distribution under certain regularity conditions
      approximates the joint distribution of interest. In Kolassa and Tanner (1994),
      the Gibbs sampler was used in conjunction with these univariate conditional
      distribution function approximations. The method of this paper does not require
      the construction and simulation of a Markov chain, thus avoiding the need to
      develop regularity conditions under which the algorithm converges and the need
      for the data analyst to check convergence of the particular chain. Examples
      involving logistic and truncated Poisson regression are presented.

PMID- 11318163
TI  - Poisson regression with missing durations of exposure.
AB  - In this paper, we develop Poisson-type regression methods that require the
      durations of exposure be measured only on a possibly nonrandom subset of the
      cohort members. These methods can be used to make inferences about the incidence
      density during exposure as well as the ratio of incidence densities during
      exposure versus not during exposure. Numerical studies demonstrate that the
      proposed methods yield reliable results in practical settings. We describe an
      application to a population-based case-control study assessing the transient
      increase in the risk of primary cardiac arrest during leisure-time physical
      activity.

PMID- 11318164
TI  - Robustness of the latent variable model for correlated binary data.
AB  - The marginal regression model offers a useful alternative to conditional
      approaches to analyzing binary data (Liang, Zeger, and Qaqish, 1992, Journal of
      the Royal Statistical Society, Series B 54, 3-40). Instead of modelling the
      binary data directly as do Liang and Zeger (1986, Biometrika 73, 13-22), the
      parametric marginal regression model developed by Qu et al. (1992, Biometrics 48,
      1095-1102) assumes that there is an underlying multivariate normal vector that
      gives rise to the observed correlated binary outcomes. Although this parametric
      approach provides a flexible way to model different within-cluster correlation
      structures and does not restrict the parameter space, it is of interest to know
      how robust the parameter estimates are with respect to choices of the latent
      distribution. We first extend the latent modelling to include multivariate t
      distributed latent vectors and assess the robustness in this class of
      distributions. Then we show through a simulation that the parameter estimates are
      robust with respect to the latent distribution even if latent distribution is
      skewed. In addtion to this empirical evidence for robustness, we show through the
      iterative algorithm that the robustness of the regression coefficents with
      respect to misspecifications of covariance structure in Liang and Zeger's model
      in fact indicates robustness with respect to underlying distributional
      assumptions of the latent vector in the latent variable model.

PMID- 11318165
TI  - Unconditional versions of several tests commonly used in the analysis of
      contingency tables.
AB  - By focusing on a confidence interval for a nuisance parameter, Berger and Boos
      (1994, Journal of the American Statistical Association 89, 1012-1016) proposed
      new unconditional tests. In particular, they showed that, for a 2 x 2 table, this
      procedure generally was more powerful than Fisher's exact test. This paper
      utilizes and extends their approach to obtain unconditional tests for combining
      several 2 x 2 tables and testing for trend and homogeneity in a 2 x K table. The
      unconditional procedures are compared to the conditional ones by reanalyzing some
      published biomedical data.

PMID- 11318166
TI  - A hierarchical Bayesian model for combining multiple 2 x 2 tables using
      conditional likelihoods.
AB  - This paper introduces a hierarchical Bayesian model for combining multiple 2 x 2
      tables that allows the flexibility of different odds ratio estimates for
      different tables and at the same time allows the tables to borrow information
      from each other. The proposed model, however, is different from a full Bayesian
      model in that the nuisance parameters are eliminated by conditioning instead of
      integration. The motivation is a more robust model and a faster and more stable
      Gibbs algorithm. We work out a Gibbs scheme using the adaptive rejection sampling
      for log concave density and an algorithm for the mean and variance of the
      noncentral hypergeometric distribution. The model is applied to a multicenter
      ulcer clinical trial.

PMID- 11318167
TI  - A note on an exact test and confidence interval for competition and overlap
      effects.
AB  - A method has been proposed that gives an exact test and confidence interval for
      the coefficient of overlap and competition effects. The method is based on
      Tukey's statistic of nonadditivity. The method is very simple to adopt and can be
      implemented by regression analysis and analysis of variance programmes in some
      important cases.

PMID- 11318168
TI  - A group sequential test for survival trials: an alternative to rank-based
      procedures.
AB  - A method of interim monitoring is described for survival trials in which the
      proportional hazards assumption may not hold. This method extends the test
      statistics based on the cumulative weighted difference in the Kaplan-Meier
      estimates (Pepe and Fleming, 1989, Biometrics 45, 497-507) to the sequential
      setting. Therefore, it provides a useful alternative to the group sequential
      linear rank tests. With an appropriate weight function, the test statistic itself
      provides an estimator for the cumulative weighted difference in survival
      probabilities, which is an interpretable measure for the treatment difference,
      especially when the proportional hazards model fails. The method is illustrated
      based on the design of a real trial. The operating characteristics are studied
      through a small simulation.

PMID- 11318169
TI  - The utility of mixed-form likelihoods.
AB  - We highlight a feature of likelihood-based methods that provides flexibility in
      model formulation and inference. In particular, overall likelihoods that consist
      of likelihood contributions with different forms are considered. The particular
      forms may be predetermined by design criteria or may be selected based on
      features of the data. Inferences based on such mixed-form likelihoods are valid
      provided standard regularity conditions hold and the parameters of interest have
      the same interpretation in the various forms. The advantages of constructing
      overall likelihoods in this way are illustrated by applications involving the
      analysis of 2 x 2 x K tables and left-censored water quality data.

PMID- 11318170
TI  - Power and sample size for testing homogeneity of relative risks in prospective
      studies.
AB  - Power and sample-size formulas for testing the homogeneity of relative risks
      using the score method are presented. The homogeneity score test (Gart, 1985,
      Biometrika 72, 673-677) is formally equivalent to the Pearson chi-square test,
      although they look different. Results of this paper may be useful in assessing
      the validity of the model of a common relative risk before combining several 2 x
      2 tables or in designing a prospective study for detecting heterogeneity of
      relative risks.

PMID- 11318171
TI  - Hazard models for line transect surveys with independent observers.
AB  - The likelihood function for data from independent observer line transect surveys
      is derived, and a hazard model is proposed for the situation where animals are
      available for detection only at discrete time points. Under the assumption that
      the time points of availability follow a Poisson point process, we obtain an
      analytical expression for the detection function. We discuss different criteria
      for choosing the hazard function and consider in particular two different
      parametric families of hazard functions. Discrete and continuous hazard models
      are compared and the robustness of the discrete model is investigated. Finally,
      the methodology is applied to data from a survey for minke whales in the
      northeastern Atlantic.

PMID- 11318172
TI  - The use of mixed logit models to reflect heterogeneity in capture-recapture
      studies.
AB  - We examine issues in estimating population size N with capture-recapture models
      when there is variable catchability among subjects. We focus on a logistic-normal
      mixed model, for which the logit of the probability of capture is an additive
      function of a random subject and a fixed sampling occasion parameter. When the
      probability of capture is small or the degree of heterogeneity is large, the log
      likelihood surface is relatively flat and it is difficult to obtain much
      information about N. We also discuss a latent class model and a log-linear model
      that account for heterogeneity and show that the log-linear model has greater
      scope. Models assuming homogeneity provide much narrower intervals for N but are
      usually highly overly optimistic, the actual coverage probability being much
      lower than the nominal level.

PMID- 11318173
TI  - Analyzing k (2 x 2) tables under cluster sampling.
AB  - In many data analytic applications, such as ophthalmologic, longitudinal, or
      periodontal studies, multiple observations are recorded over several sites (or
      timepoints) within the same subject, bringing about dependence between
      measurements. This correlation, in turn, precludes the use of standard
      statistical methods that assume independence between outcome measurements. For
      example, the Mantel-Haenszel statistic, used to assess association between a
      binary outcome and a binary exposure while adjusting for a categorical covariate,
      does not follow the usual chi-squared distribution under the null hypothesis when
      there is correlation between observations. A modified Mantel-Haenszel procedure,
      which makes adjustment for dependence, is proposed. No particular correlation
      structure is assumed for responses within a cluster. This closed-form adjustment
      stems from Liang and Zeger's (1986, Biometrika 73, 13-22) generalized estimating
      equations approach for clustered data. The difference between this tabular (i.e.,
      noniterative) technique and many earlier tabular methods is that the current
      method allows for consideration of site-specific exposure and covariate
      information. An example from a periodontal research study illustrates application
      of the method.

PMID- 11318174
TI  - Regression modeling of ordinal data with nonzero baselines.
AB  - This paper develops regression models for ordinal data with nonzero control
      response probabilities. The models are especially useful in dose-response studies
      where the spontaneous or natural response rate is nonnegligible and the dosage is
      logarithmic. These models generalize Abbott's formula, which has been commonly
      used to model binary data with nonzero background observations. We describe a
      biologically plausible latent structure and develop an EM algorithm for fitting
      the models. The EM algorithm can be implemented using standard software for
      ordinal regression. A toxicology data set where the proposed model fits the data
      but a more conventional model fails is used to illustrate the methodology.

PMID- 11318175
TI  - Maximally selected chi2 statistics for k x 2 tables.
AB  - It is common in epidemiologic analyses to summarize continuous outcomes as
      falling above or below a threshold. With such a dichotomized outcome, the usual
      chi2 statistics for association or trend can be used to test for equality of
      proportions across strata of the study population. However, if the threshold is
      chosen to maximize the test statistic, the nominal chi2 reference distributions
      are incorrect. In this paper, the asymptotic distributions of maximally selected
      chi2 statistics for association and for trend for the k x 2 table are derived.
      The methodology is illustrated with data from an AIDS clinical trial. The results
      of simulation experiments that assess the accuracy of the asymptotic
      distributions in moderate sample sizes are also reported.

PMID- 11318176
TI  - Estimation of offspring production from a limited number of stage-structured
      censuses.
AB  - We propose a procedure for maximum likelihood estimation of the number of animals
      or offspring in a closed population where the individuals counted go through
      stages or age-groups. Application of the procedure requires knowledge of the
      distributions of the stage durations. A procedure for maximum likelihood
      estimation of those based on marked animals is also given. The procedures are
      illustrated by applying them to gray seal (Halichoerus grypus) data from Froan
      Nature Reserve, Central Norway, from the breeding seasons 1990-1999.

PMID- 11318177
TI  - A model for thermograms.
AB  - Thermograms are curves resulting from thermal analysis and are of great interest
      in the study of various food and biological products physical properties. A
      method to separate underlying peaks is proposed, and statistical properties of
      estimates for some characteristic parameters are derived. The total number of
      peaks can be estimated with a sequential analysis of the residual plots. For each
      new peak, a statistical criterion is proposed to check whether it is
      significantly different from the noise of the recording. As an example, the
      method is applied to a summer milk fat fusion thermogram.

PMID- 11318178
TI  - Flexible parametric measurement error models.
AB  - Inferences in measurement error models can be sensitive to modeling assumptions.
      Specifically, if the model is incorrect, the estimates can be inconsistent. To
      reduce sensitivity to modeling assumptions and yet still retain the efficiency of
      parametric inference, we propose using flexible parametric models that can
      accommodate departures from standard parametric models. We use mixtures of
      normals for this purpose. We study two cases in detail: a linear errors-in
      variables model and a change-point Berkson model.

PMID- 11318179
TI  - Genetic models with reduced penetrance related to the Y chromosome.
AB  - Classical statistical genetics models of a quantitative trait depending on an
      autosomal gene indicate that father-to-daughter and mother-to-son correlations
      should be the same. If phenotypes are not sex-dependent, father-to-son and mother
      to-daughter correlations also share this common value. On the other hand, if the
      gene is sex-linked, then the father-to-son correlation is zero. Such models do
      not explain genetic variation in pulmonary artery pressure (PAP) of cattle-
      important because cattle with high PAP are known to develop brisket disease,
      pulmonary heart disease, and congestive heart failure when taken to high
      altitudes. Data on 966 calves at a ranch in Colorado showed positive correlation
      (0.2) between sire PAP and male calf PAP but slightly negative correlation (
      0.01) between sire PAP and female calf PAP; the dam-to-male calf and dam-to
      female calf correlations are both about 0.1. The model presented here postulates
      an autosomal gene with reduced penetrance (i.e., the trait may remain at a normal
      level even when the genotype suggests abnormality) and that, in males, the rate
      of penetrance is related to an abnormality in the Y chromosome and is therefore
      passed on from father to son. Then under plausible selective breeding
      assumptions, the pairwise correlation between fathers and daughters can become
      zero or negative. Explicit formulas are computed for the model covariances, and
      numerical computations indicate that plausible parameter values can be chosen for
      the model.

PMID- 11318180
TI  - Hypothesis testing under mixture models: application to genetic linkage analysis.
AB  - In this paper we propose a new class of statistics to test a simple hypothesis
      against a family of alternatives characterized by a mixture model. Unlike the
      likelihood ratio statistic, whose large sample distribution is still unknown in
      this situation, these new statistics have a simple asymptotic distribution to
      which to refer under the null hypothesis. Simulation results suggest that it has
      adequate power in detecting the alternatives. Its application to genetic linkage
      analysis in the presence of the genetic heterogeneity that motivated this work is
      emphasized.

PMID- 11318181
TI  - Use of summary measures to adjust for informative missingness in repeated
      measures data with random effects.
AB  - We discuss how to apply the conditional informative missing model of Wu and
      Bailey (1989, Biometrics 45, 939-955) to the setting where the probability of
      missing a visit depends on the random effects of the primary response in a time
      dependent fashion. This includes the case where the probability of missing a
      visit depends on the true value of the primary response. Summary measures for
      missingness that are weighted sums of the indicators of missed visits are derived
      for these situations. These summary measures are then incorporated as covariates
      in a random effects model for the primary response. This approach is illustrated
      by analyzing data collected from a trial of heroin addicts where missed visits
      are informative about drug test results. Simulations of realistic experiments
      indicate that these time-dependent summary measures also work well under a
      variety of informative censoring models. These summary measures can achieve large
      reductions in estimation bias and mean squared errors relative to those obtained
      by using other summary measures.

PMID- 11318182
TI  - Mixed effects models with bivariate and univariate association parameters for
      longitudinal bivariate binary response data.
AB  - When two binary responses are measured for each study subject across time, it may
      be of interest to model how the bivariate associations and marginal univariate
      risks involving the two responses change across time. To achieve such a goal,
      marginal models with bivariate log odds ratio and univariate logit components are
      extended to include random effects for all components. Specifically, separate
      normal random effects are specified on the log odds ratio scale for bivariate
      responses and on the logit scale for univariate responses. Assuming conditional
      independence given the random effects facilitates the modeling of bivariate
      associations across time with missing at random incomplete data. We fit the model
      to a dataset for which such structures are feasible: a longitudinal randomized
      trial of a cardiovascular educational program where the responses of interest are
      change in hypertension and hypercholestemia status. The proposed model is
      compared to a naive bivariate model that assumes independence between time points
      and univariate mixed effects logit models.

PMID- 11318183
TI  - Semiparametric methods for multiple exposure mismeasurement and a bivariate
      outcome in HIV vaccine trials.
AB  - Exposure to infection information is important for estimating vaccine efficacy,
      but it is difficult to collect and prone to missingness and mismeasurement. We
      discuss study designs that collect detailed exposure information from only a
      small subset of participants while collecting crude exposure information from all
      participants and treat estimation of vaccine efficacy in the missing
      data/measurement error framework. We extend the discordant partner design for HIV
      vaccine trials of Golm, Halloran, and Longini (1998, Statistics in Medicine, 17,
      2335-2352.) to the more complex augmented trial design of Longini, Datta, and
      Halloran (1996, Journal of Acquired Immune Deficiency Syndromes and Human
      Retrovirology 13, 440-447) and Datta, Halloran, and Longini (1998, Statistics in
      Medicine 17, 185-200). The model for this design includes three exposure
      covariates and both univariate and bivariate outcomes. We adapt recently
      developed semiparametric missing data methods of Reilly and Pepe (1995,
      Biometrika 82, 299 314), Carroll and Wand (1991, Journal of the Royal Statistical
      Society, Series B 53, 573-585), and Pepe and Fleming (1991, Journal of the
      American Statistical Association 86, 108-113) to the augmented vaccine trial
      design. We demonstrate with simulated HIV vaccine trial data the improvements in
      bias and efficiency when combining the different levels of exposure information
      to estimate vaccine efficacy for reducing both susceptibility and infectiousness.
      We show that the semiparametric methods estimate both efficacy parameters without
      bias when the good exposure information is either missing completely at random or
      missing at random. The pseudolikelihood method of Carroll and Wand (1991) and
      Pepe and Fleming (1991) was the more efficient of the two semiparametric methods.

PMID- 11318184
TI  - Evolution and biometry.

PMID- 11318185
TI  - Matrix methods for estimating odds ratios with misclassified exposure data:
      extensions and comparisons.
AB  - Misclassification of exposure variables is a common problem in epidemiologic
      studies. This paper compares the matrix method (Barron, 1977, Biometrics 33, 414
      418; Greenland, 1988a, Statistics in Medicine 7, 745-757) and the inverse matrix
      method (Marshall, 1990, Journal of Clinical Epidemiology 43, 941-947) to the
      maximum likelihood estimator (MLE) that corrects the odds ratio for bias due to a
      misclassified binary covariate. Under the assumption of differential
      misclassification, the inverse matrix method is always more efficient than the
      matrix method; however, the efficiency depends strongly on the values of the
      sensitivity, specificity, baseline probability of exposure, the odds ratio, case
      control ratio, and validation sampling fraction. In a study on sudden infant
      death syndrome (SIDS), an estimate of the asymptotic relative efficiency (ARE) of
      the inverse matrix estimate was 0.99, while the matrix method's ARE was 0.19.
      Under nondifferential misclassification, neither the matrix nor the inverse
      matrix estimator is uniformly more efficient than the other; the efficiencies
      again depend on the underlying parameters. In the SIDS data, the MLE was more
      efficient than the matrix method (ARE = 0.39). In a study investigating the
      effect of vitamin A intake on the incidence of breast cancer, the MLE was more
      efficient than the matrix method (ARE = 0.75).

PMID- 11318186
TI  - Nonparametric estimation of a delay distribution based on left-censored and right
      truncated data.
AB  - This paper proposes a nonparametric method for estimating a delay distribution
      based on left-censored and right-truncated data. A variance-covariance estimator
      is provided. The method is applied to the Australian AIDS data in which some data
      are left censored and some data are not left censored. This situation arises with
      AIDS case-reporting data in Australia because reporting delays were recorded only
      from November 1990 rather than from the beginning of the epidemic there. It is
      shown that inclusion of the left-censored data, as opposed to analyzing only the
      uncensored data, improves the precision of the estimate.

PMID- 11318187
TI  - Optimal diversity-dependent contributions of genotypes to mixtures.
AB  - Deployment of genotypes to a production population decisively depends on the
      measure of diversity, a consideration that parallels genetic gain in the
      management of genotype mixtures. Optimal diversity-dependent deployment has been
      developed in this study for a family of diversity indices in the genetical and
      ecological context. The optimal solution at given diversity was expressed as the
      relationship between genotype contributions and their genetic performances, which
      maximized genetic gain. Numerical calculations were performed by using genotypes
      generated from normal order statistics. An optimal deployment in one situation
      could be nonoptimum in another. Classical uniform deployment, where superior
      genotypes equally contribute to the mixtures, was the limit of optimal
      deployment. Comparisons were made between optimal and uniform deployment and
      between optimal and nonoptimal deployment where genotypes contributed
      proportionally to the mixtures in accordance to their genetic superiority. The
      superiority in gain of optimal deployment over that of uniform deployment
      increased as the difference between the diversity measure under optimal
      deployment and the contributing number (N) of genotypes under uniform deployment
      became large and as the diversity measure and N under optimal deployment
      increased. The superiority over nonoptimal deployment increased rapidly at low
      diversity, reaching a maximum somewhere at diversity between 1 and N. Scale of
      superiority depended on the similitude between optimum and nonoptimum deployment;
      the larger the distinctiveness, the greater the superiority.

PMID- 11318188
TI  - A multiplicative-epistatic model for analyzing interspecific differences in
      outcrossing species.
AB  - Epistasis may play an important role in evolution and speciation. Under
      multiplicative interactions between different loci, an analytical model is
      proposed to estimate genetic parameters at the individual locus level that
      contribute to interspecific differences in outcrossing species. The
      multiplicative epistasis model, inferred from a number of animal and plant
      experiments, suggests that genotypes at a pair of loci have genotypic values
      equal to the product of genotypic values at the two different loci. By
      considering the genetic property of outcrossing species (i.e., high
      polymorphisms) in the multilevel family structure analysis for an intra- and
      interspecific factorial mating design, a method is developed to provide estimates
      for allele frequencies and additive and dominant effects at individual loci in
      each of the two parental populations, the genotypic values of newly formed
      heterozygotes through species combination each with one allele from a parental
      population and the second from the other parental population, and the numbers of
      genetic factors that lead to species differentiation. Use of clones offers a
      tremendous power to test the adequacy of the model. However, the utilization of
      the model with species that cannot be cloned is also discussed. An example with
      interspecific hybrids of two forest tree species is used to demonstrate the
      model.

PMID- 11318189
TI  - A goodness-of-fit test for capture-recapture model Mt under closure.
AB  - A new, fully efficient goodness-of-fit test for the time-specific closed
      population capture-recapture model Mt is presented. This test is based on the
      residual distribution of the capture history data given the maximum likelihood
      parameter estimates under model Mt, is partitioned into informative components,
      and is based on chi-square statistics. Comparison of this test with Leslie's test
      (Leslie, 1958, Journal of Animal Ecology 27, 84-86) for model Mt, using Monte
      Carlo simulations, shows the new test generally outperforms Leslie's test. The
      new test is frequently computable when Leslie's test is not, has Type I error
      rates that are closer to nominal error rates than Leslie's test, and is sensitive
      to behavioral variation and heterogeneity in capture probabilities. Leslie's test
      is not sensitive to behavioral variation in capture probabilities but, when
      computable, has greater power to detect heterogeneity than the new test.

PMID- 11318190
TI  - A study of deleterious gene structure in plants using Markov chain Monte Carlo.
AB  - The characteristics of deleterious genes have been of great interest in both
      theory and practice in genetics. Because of the complex genetic mechanism of
      these deleterious genes, most current studies try to estimate the overall
      magnitude of mortality effects on a population, which is characterized
      classically by the number of lethal equivalents. This number is a combination of
      several parameters, each of which has a distinct biological effect on genetic
      mortality. In conservation and breeding programs, it is important to be able to
      distinguish among different combinations of these parameters that lead to the
      same number of lethal equivalents, such as a large number of mildly deleterious
      genes or a few lethal genes, The ability to distinguish such parameter
      combinations requires more than one generation of mating. We propose a model for
      survival data from a two-generation mating experiment on the plant species
      Brassica rapa, and we enable inference with Markov chain Monte Carlo. This
      computational strategy is effective because a vast amount of missing genotype
      information must be accounted for. In addition to the lethal equivalents, the two
      generation data provide separate information on the average intensity of
      mortality and the average number of deleterious genes carried by an individual.
      In our Markov chain Monte Carlo algorithm, we use a vector proposal distribution
      to overcome inefficiency of a single-site Gibbs sampler. Information about
      environmental effects is obtained from an outcrossing experiment conducted in
      parallel with the two-generation mating experiments.

PMID- 11318191
TI  - Estimation of the size of an open population from capture-recapture data using
      weighted martingale methods.
AB  - A weighted martingale method, akin to a moving average, is proposed to allow the
      use of modified closed-population methods in the estimation of the size of a
      smoothly changing open population when there are frequent capture occasions. We
      concentrate here on modifications to martingale estimating functions for model
      Mt, but a wide range of closed-population estimators may be modified in this
      fashion. The method is motivated by and applied to weekly capture-recapture data
      from the Mai Po bird sanctuary in Hong Kong. Simulations show that the weighted
      martingale estimator compared well with the Jolly-Seber estimator when the
      conditions for the latter to be valid are met, and it performed far better when
      individuals were allowed to leave and reenter the population. Expressions are
      derived for the asymptotic bias and variance of the estimator in an appendix.

PMID- 11318192
TI  - Two-stage design of quantal response studies.
AB  - In a quantal response study, there may be insufficient knowledge of the response
      relationship for the stimulus (or dose) levels to be chosen properly. Information
      from such a study can be scanty or even unreliable. A two-stage design is
      proposed for such studies, which can determine whether and how a follow-up (i.e.,
      second-stage) study should be conducted to select additional stimulus levels to
      compensate for the scarcity of information in the initial study. These levels are
      determined by using optimal design theory and are based on the fitted model from
      the data in the initial study. Its advantages are demonstrated using a fishery
      study.

PMID- 11318193
TI  - Repeated probit regression when covariates are measured with error.
AB  - This paper develops a model for repeated binary regression when a covariate is
      measured with error. The model allows for estimating the effect of the true value
      of the covariate on a repeated binary response. The choice of a probit link for
      the effect of the error-free covariate, coupled with normal measurement error for
      the error-free covariate, results in a probit model after integrating over the
      measurement error distribution. We propose a two-stage estimation procedure
      where, in the first stage, a linear mixed model is used to fit the repeated
      covariate. In the second stage, a model for the correlated binary responses
      conditional on the linear mixed model estimates is fit to the repeated binary
      data using generalized estimating equations. The approach is demonstrated using
      nutrient safety data from the Diet Intervention of School Age Children (DISC)
      study.

PMID- 11318194
TI  - Population HIV-1 dynamics in vivo: applicable models and inferential tools for
      virological data from AIDS clinical trials.
AB  - In this paper, we introduce a novel application of hierarchical nonlinear mixed
      effect models to HIV dynamics. We show that a simple model with a sum of
      exponentials can give a good fit to the observed clinical data of HIV-1 dynamics
      (HIV-1 RNA copies) after initiation of potent antiviral treatments and can also
      be justified by a biological compartment model for the interaction between HIV
      and its host cells. This kind of model enjoys both biological interpretability
      and mathematical simplicity after reparameterization and simplification. A model
      simplification procedure is proposed and illustrated through examples. We
      interpret and justify various simplified models based on clinical data taken
      during different phases of viral dynamics during antiviral treatments. We suggest
      the hierarchical nonlinear mixed-effect model approach for parameter estimation
      and other statistical inferences. In the context of an AIDS clinical trial
      involving patients treated with a combination of potent antiviral agents, we show
      how the models may be used to draw biologically relevant interpretations from
      repeated HIV-1 RNA measurements and demonstrate the potential use of the models
      in clinical decision-making.

PMID- 11318195
TI  - A Bayesian approach to ordering gene markers.
AB  - A technique is presented whereby a marker map can be constructed using resource
      family data with an entire class of missing data. The focus is on a half-sib
      design where there is only information on a single parent and its progeny. A
      Bayesian approach is utilised with solutions obtained via a Markov chain Monte
      Carlo algorithm. Features of the approach include the capacity to determine
      parameters for the ungenotyped dam population, the ability to incorporate
      published information and its reliability, and the production of posterior
      densities and the consequent deduction of a wide range of inferences. These
      features are demonstrated through the analysis of simulated and experimental
      data.

PMID- 11318196
TI  - Symmetric tests and confidence intervals for survival probabilities and quantiles
      of censored survival data.
AB  - We describe existing tests and introduce two new tests concerning the value of a
      survival function. These tests may be used to construct a confidence interval for
      the survival probability at a given time or for a quantile of the survival
      distribution. Simulation studies show that error rates can differ substantially
      from their nominal values, particularly at survival probabilities close to zero
      or one. We recommend our new constrained bootstrap test for its good overall
      performance.

PMID- 11318197
TI  - Optimum experimental designs for multinomial logistic models.
AB  - Multinomial responses frequently occur in dose level experiments. For example, in
      a study of the influence of gamma radiation on the emergence of house flies
      (Musca domestica L., 1758), three disjoint outcomes occurred: death before the
      pupae opened, death during emergence, and life after emergence. Although the
      flies are easy to breed, this sort of bioassay is, in general, very expensive
      since it requires the use of a gamma radiation source. Experiments therefore need
      to be designed to involve the minimum number of different doses. Here the theory
      of optimum experimental design is applied to provide efficient experiments to
      estimate the parameters of those multinomial logistic models that are a special
      case of the multivariate logistic models of Glonek and McCullagh (1995, Journal
      of the Royal Statistical Society, Series B 57, 533-546). The purpose is to reduce
      the overall experimental cost. The general equivalence theorem (Fedorov, 1972,
      Theory of Optimal Experiments) is adapted to this class of models, providing an
      effective method of generating and checking the optimality of designs. One
      example on flies demonstrates the method, which can be easily implemented.

PMID- 11318198
TI  - Applying the Cox proportional hazards model when the change time of a binary time
      varying covariate is interval censored.
AB  - This paper develops methodology for estimation of the effect of a binary time
      varying covariate on failure times when the change time of the covariate is
      interval censored. The motivating example is a study of cytomegalovirus (CMV)
      disease in patients with human immunodeficiency virus (HIV) disease. We are
      interested in determining whether CMV shedding predicts an increased hazard for
      developing active CMV disease. Since a clinical screening test is needed to
      detect CMV shedding, the time that shedding begins is only known to lie in an
      interval bounded by the patient's last negative and first positive tests. In a
      Cox proportional hazards model with a time-varying covariate for CMV shedding,
      the partial likelihood depends on the covariate status of every individual in the
      risk set at each failure time. Due to interval censoring, this is not always
      known. To solve this problem, we use a Monte Carlo EM algorithm with a Gibbs
      sampler embedded in the E-step. We generate multiple completed data sets by
      drawing imputed exact shedding times based on the joint likelihood of the
      shedding times and event times under the Cox model. The method is evaluated using
      a simulation study and is applied to the data set described above.

PMID- 11318199
TI  - Analysis of infant growth curves using multivariate adaptive splines.
AB  - In this paper, we study the effect of cocaine use by a pregnant woman on the
      growth of her infant after birth. Using a data set from a retrospective study, we
      found that cocaine use was a marginally significant contributor to the infant
      growth as measured by bodyweight. From a statistical point of view, the data
      represent a common, though complex, structure that has received little attention
      in the statistical literature. To analyze these data, we adopt and further
      enhance an approach developed recently called MASAL (multivariate adaptive
      splines for the analysis of longitudinal data). In addition to the fitting of
      growth curves, we demonstrate particularly how to explore and estimate the
      underlying covariance structures for the longitudinal data that were collected
      from a rather irregular schedule.

PMID- 11318200
TI  - Adjusted regression trend test for a multicenter clinical trial.
AB  - Studies using a series of increasing doses of a compound, including a zero dose
      control, are often conducted to study the effect of the compound on the response
      of interest. For a one-way design, Tukey et al. (1985, Biometrics 41, 295-301)
      suggested assessing trend by examining the slopes of regression lines under
      arithmetic, ordinal, and arithmetic-logarithmic dose scalings. They reported the
      smallest p-value for the three significance tests on the three slopes for safety
      assessments. Capizzi et al. (1992, Biometrical Journal 34, 275-289) suggested an
      adjusted trend test, which adjusts the p-value using a trivariate t-distribution,
      the joint distribution of the three slope estimators. In this paper, we propose
      an adjusted regression trend test suitable for two-way designs, particularly for
      multicenter clinical trials. In a step-down fashion, the proposed trend test can
      be applied to a multicenter clinical trial to compare each dose with the control.
      This sequential procedure is a closed testing procedure for a trend alternative.
      Therefore, it adjusts p-values and maintains experimentwise error rate.
      Simulation results show that the step-down trend test is overall more powerful
      than a step-down least significant difference test.

PMID- 11318201
TI  - Finite mixture modeling with mixture outcomes using the EM algorithm.
AB  - This paper discusses the analysis of an extended finite mixture model where the
      latent classes corresponding to the mixture components for one set of observed
      variables influence a second set of observed variables. The research is motivated
      by a repeated measurement study using a random coefficient model to assess the
      influence of latent growth trajectory class membership on the probability of a
      binary disease outcome. More generally, this model can be seen as a combination
      of latent class modeling and conventional mixture modeling. The EM algorithm is
      used for estimation. As an illustration, a random-coefficient growth model for
      the prediction of alcohol dependence from three latent classes of heavy alcohol
      use trajectories among young adults is analyzed.

PMID- 11318202
TI  - An empirical comparison of several clustered data approaches under confounding
      due to cluster effects in the analysis of complications of coronary angioplasty.
AB  - In the analysis of binary response data from many types of large studies, the
      data are likely to have arisen from multiple centers, resulting in a within
      center correlation for the response. Such correlation, or clustering, occurs when
      outcomes within centers tend to be more similar to each other than to outcomes in
      other centers. In studies where there is also variability among centers with
      respect to the exposure of interest, analysis of the exposure-outcome association
      may be confounded, even after accounting for within-center correlations. We apply
      several analytic methods to compare the risk of major complications associated
      with two strategies, staged and combined procedures, for performing percutaneous
      transluminal coronary angioplasty (PTCA), a mechanical means of relieving
      blockage of blood vessels due to atherosclerosis. Combined procedures are used in
      some centers as a cost-cutting strategy. We performed a number of population
      averaged and cluster-specific (conditional) analyses, which (a) make no
      adjustments for center effects of any kind; (b) make adjustments for the effect
      of center on only the response; or (c) make adjustments for both the effect of
      center on the response and the relationship between center and exposure. The
      method used for this third approach decomposes the procedure type variable into
      within-center and among-center components, resulting in two odds ratio estimates.
      The naive analysis, ignoring clusters, gave a highly significant effect of
      procedure type (OR = 1.6). Population average models gave marginally to very
      nonsignificant estimates of the OR for treatment type ranging from 1.6 to 1.2
      with adjustment only for the effect of centers on response. These results
      depended on the assumed correlation structure. Conditional (cluster-specific)
      models and other methods that decomposed the treatment type variable into among-
      and within-center components all found no within-center effect of procedure type
      (OR = 1.02, consistently) and a considerable among-center effect. This among
      center variability in outcomes was related to the proportion of patients who
      receive combined procedures and was found even when conditioned on procedure type
      (within-center) and other patient- and center-level covariates. This example
      illustrates the importance of addressing the potential for center effects to
      confound an outcome-exposure association when average exposure varies across
      clusters. While conditional approaches provide estimates of the within-cluster
      effect, they do not provide information about among-center effects. We recommend
      using the decomposition approach, as it provides both types of estimates.

PMID- 11318203
TI  - A Bayesian semiparametric accelerated failure time model.
AB  - A Bayesian semiparametric approach is described for an accelerated failure time
      model. The error distribution is assigned a Polya tree prior and the regression
      parameters a noninformative hierarchical prior. Two cases are considered: the
      first assumes error terms are exchangeable; the second assumes that error terms
      are partially exchangeable. A Markov chain Monte Carlo algorithm is described to
      obtain a predictive distribution for a future observation given both uncensored
      and censored data.

PMID- 11318204
TI  - Bayesian design and analysis of active control clinical trials.
AB  - We consider the design and analysis of active control clinical trials, i.e.,
      clinical trials comparing an experimental treatment E to a control treatment C
      considered to be effective. Direct comparison of E to placebo P, or no treatment,
      is sometimes ethically unacceptable. Much discussion of the design and analysis
      of such clinical trials has focused on whether the comparison of E to C should be
      based on a test of the null hypothesis of equivalence, on a test of a nonnull
      hypothesis that the difference is of some minimally medically important size
      delta, or on one or two-sided confidence intervals. These approaches are
      essentially the same for study planning. They all suffer from arbitrariness in
      specifying the size of the difference delta that must be excluded. We propose an
      alternative Bayesian approach to the design and analysis of active control
      trials. We derive the posterior probability that E is superior to P or that E is
      at least k% as good as C and that C is more effective than P. We also derive
      approximations for use with logistic and proportional hazard models. Selection of
      prior distributions is discussed, and results are illustrated using data from an
      active control trial of a drug for the treatment of unstable angina.

PMID- 11318205
TI  - Generalized estimating equations for ordinal categorical data: arbitrary patterns
      of missing responses and missingness in a key covariate.
AB  - We propose methods for regression analysis of repeatedly measured ordinal
      categorical data when there is nonmonotone missingness in these responses and
      when a key covariate is missing depending on observables. The methods use ordinal
      regression models in conjunction with generalized estimating equations (GEEs). We
      extend the GEE methodology to accommodate arbitrary patterns of missingness in
      the responses when this missingness is independent of the unobserved responses.
      We further extend the methodology to provide correction for possible bias when
      missingness in knowledge of a key covariate may depend on observables. The
      approach is illustrated with the analysis of data from a study in diagnostic
      oncology in which multiple correlated receiver operating characteristic curves
      are estimated and corrected for possible verification bias when the true disease
      status is missing depending on observables.

PMID- 11318207
TI  - Fitting semi-Markov models to interval-censored data with unknown initiation
      times.
AB  - In a semi-Markov model, the hazard of making a transition between stages depends
      on the time spent in the current stage but is independent of time spent in other
      stages. If the initiation time (time of entry into the network) is not known for
      some persons and if transition time data are interval censored (i.e., if
      transition times are not known exactly but are known only to have occurred in
      some interval), then the length of time these persons spent in any stage is not
      known. We show how a semi-Markov model can still be fit to interval-censored data
      with missing initiation times. For the special case of models in which all
      persons enter the network at the same initial stage and proceed through the same
      succession of stages to a unique absorbing stage, we present discrete-time
      nonparametric maximum likelihood estimators of the waiting-time distributions for
      this type of data.

PMID- 11318206
TI  - Modeling random effects for censored data by a multivariate normal regression
      model.
AB  - A normal distribution regression model with a frailty-like factor to account for
      statistical dependence between the observed survival times is introduced. This
      model, as opposed to standard hazard-based frailty models, has survival times
      that, conditional on the shared random effect, have an accelerated failure time
      representation. The dependence properties of this model are discussed and maximum
      likelihood estimation of the model's parameters is considered. A number of
      examples are considered to illustrate the approach. The estimated degree of
      dependence is comparable to other models, but the present approach has the
      advantage that the interpretation of the random effect is simpler than in the
      frailty model.

PMID- 11318208
TI  - Discrete-time nonparametric estimation for semi-Markov models of chain-of-events
      data subject to interval censoring and truncation.
AB  - Chain-of-events data are longitudinal observations on a succession of events that
      can only occur in a prescribed order. One goal in an analysis of this type of
      data is to determine the distribution of times between the successive events.
      This is difficult when individuals are observed periodically rather than
      continuously because the event times are then interval censored. Chain-of-events
      data may also be subject to truncation when individuals can only be observed if a
      certain event in the chain (e.g., the final event) has occurred. We provide a
      nonparametric approach to estimate the distributions of times between successive
      events in discrete time for data such as these under the semi-Markov assumption
      that the times between events are independent. This method uses a self
      consistency algorithm that extends Turnbull's algorithm (1976, Journal of the
      Royal Statistical Society, Series B 38, 290-295). The quantities required to
      carry out the algorithm can be calculated recursively for improved computational
      efficiency. Two examples using data from studies involving HIV disease are used
      to illustrate our methods.

PMID- 11318209
TI  - New residuals for Cox regression and their application to outlier screening.
AB  - The identification of individuals who 'died far too early' or 'lived far too
      long' as compared to their survival probabilities from a Cox regression can lead
      to the detection of new prognostic factors. Methods to identify outliers are
      generally based on residuals. For Cox regression, only deviance residuals have
      been considered for this purpose, but we show that these residuals are not very
      suitable. Instead, we develop and propose two new types of residuals: the
      suggested log-odds and normal deviate residuals are simple and intuitively
      appealing and their theoretical properties and empirical performance make them
      very suitable for outlier identification. Finally, various practical aspects of
      screening for individuals with outlying survival times are discussed by means of
      a cancer study example.

PMID- 11318210
TI  - Locally efficient estimation of the quality-adjusted lifetime distribution with
      right-censored data and covariates.
AB  - Zhao and Tsiatis (1997) consider the problem of estimation of the distribution of
      the quality-adjusted lifetime when the chronological survival time is subject to
      right censoring. The quality-adjusted lifetime is typically defined as a weighted
      sum of the times spent in certain states up until death or some other failure
      time. They propose an estimator and establish the relevant asymptotics under the
      assumption of independent censoring. In this paper we extend the data structure
      with a covariate process observed until the end of follow-up and identify the
      optimal estimation problem. Because of the curse of dimensionality, no globally
      efficient nonparametric estimators, which have a good practical performance at
      moderate sample sizes, exist. Given a correctly specified model for the hazard of
      censoring conditional on the observed quality-of-life and covariate processes, we
      propose a closed-form one-step estimator of the distribution of the quality
      adjusted lifetime whose asymptotic variance attains the efficiency bound if we
      can correctly specify a lower-dimensional working model for the conditional
      distribution of quality-adjusted lifetime given the observed quality-of-life and
      covariate processes. The estimator remains consistent and asymptotically normal
      even if this latter submodel is misspecified. The practical performance of the
      estimators is illustrated with a simulation study. We also extend our proposed
      one-step estimator to the case where treatment assignment is confounded by
      observed risk factors so that this estimator can be used to test a treatment
      effect in an observational study.

PMID- 11318211
TI  - Summarizing the motion of self-propelled cells: applications to sperm motility.
AB  - Proper characterization of the motion of spermatozoa is an important prerequisite
      for interpreting differences in sperm motility that might arise from exposure to
      toxicants. Patterns of sperm movement can be extremely complex. On the basis of
      an exponential model that relates the discretely approximated curvilinear
      velocity to the tracking rate, we develop a statistic that indexes the
      predictability of the path for individual sperm. We summarize the path of each
      sperm using this and two other statistics: (1) the path displacement velocity and
      (2) linearity of movement. We apply the method to a set of rat sperm tracks
      representative of both normal and abnormal motion characteristics.

PMID- 11318212
TI  - The Knox method and other tests for space-time interaction.
AB  - The Knox method, as well as other tests for space-time interaction, are biased
      when there are geographical population shifts, i.e., when there are different
      percent population growths in different regions. In this paper, the size of the
      population shift bias is investigated for the Knox test, and it is shown that it
      can be a considerable problem. A Monte Carlo method for constructing unbiased
      space-time interaction tests is then presented and illustrated on the Knox test
      as well as for a combined Knox test. Practical implications are discussed in
      terms of the interpretation of past results and the design of future studies.

PMID- 11318213
TI  - Modeling heterogeneity in nest survival data.
AB  - Current statistical methods for estimating nest survival rates assume that nests
      are identical in their propensity to succeed. However, there are several
      biological reasons to question this assumption. For example, experience of the
      nest builder, number of nest helpers, genetic fitness of individuals, and site
      effects may contribute to an inherent disparity between nests with respect to
      their daily mortality rates. Ignoring such heterogeneity can lead to incorrect
      survival estimates. Our results show that constant survival models can seriously
      underestimate overall survival in the presence of heterogeneity. This paper
      presents a flexible random-effects approach to model heterogeneous nest survival
      data. We illustrate our methods through data on redwing blackbirds.

PMID- 11318214
TI  - Reduced sensitivity to hidden bias at upper quantiles in observational studies
      with dilated treatment effects.
AB  - When a treatment has a dilated effect, with larger effects when responses are
      higher, there can be much less sensitivity to bias at upper quantiles than at
      lower quantiles; i.e., small, plausible hidden biases might explain the
      ostensible effect of the treatment for many subjects, and yet only quite large
      hidden biases could explain the effect on a few subjects having dramatically
      elevated responses. An example concerning kidney function of cadmium workers is
      discussed in detail. In that example, the treatment effect is far from additive:
      It is plausibly zero at the lower quartile of responses to control, and it is
      large and fairly insensitive to bias at the upper quartile.

PMID- 11318215
TI  - Stochastic algorithms for Markov models estimation with intermittent missing
      data.
AB  - Multistate Markov models are frequently used to characterize disease processes,
      but their estimation from longitudinal data is often hampered by complex patterns
      of incompleteness. Two algorithms for estimating Markov chain models in the case
      of intermittent missing data in longitudinal studies, a stochastic EM algorithm
      and the Gibbs sampler, are described. The first can be viewed as a random
      perturbation of the EM algorithm and is appropriate when the M step is
      straightforward but the E step is computationally burdensome. It leads to a good
      approximation of the maximum likelihood estimates. The Gibbs sampler is used for
      a full Bayesian inference. The performances of the two algorithms are illustrated
      on two simulated data sets. A motivating example concerned with the modelling of
      the evolution of parasitemia by Plasmodium falciparum (malaria) in a cohort of
      105 young children in Cameroon is described and briefly analyzed.

PMID- 11318216
TI  - Robust regression for clustered data with application to binary responses.
AB  - Generalized estimating equations (GEE) can be highly influenced by the presence
      of unusual data points. A generalization of the GEE procedure, which yields
      parameter estimates and fitted values that are resistant to influential data, is
      introduced. Resistant generalized estimating equations (REGEE) include weights in
      the estimating equations to downweight influential observations or clusters.
      Influential observations are downweighted according to their leverage or residual
      in an example of correlated binary regression applied to 137 urinary incontinent
      elderly patients from 38 medical practices.

PMID- 11318217
TI  - A global goodness-of-fit statistic for Cox regression models.
AB  - In this paper, a global goodness-of-fit test statistic for a Cox regression
      model, which has an approximate chi-squared distribution when the model has been
      correctly specified, is proposed. Our goodness-of-fit statistic is global and has
      power to detect if interactions or higher order powers of covariates in the model
      are needed. The proposed statistic is similar to the Hosmer and Lemeshow (1980,
      Communications in Statistics A10, 1043-1069) goodness-of-fit statistic for binary
      data as well as Schoenfeld's (1980, Biometrika 67, 145-153) statistic for the Cox
      model. The methods are illustrated using data from a Mayo Clinic trial in primary
      billiary cirrhosis of the liver (Fleming and Harrington, 1991, Counting Processes
      and Survival Analysis), in which the outcome is the time until liver
      transplantation or death. The are 17 possible covariates. Two Cox proportional
      hazards models are fit to the data, and the proposed goodness-of-fit statistic is
      applied to the fitted models.

PMID- 11318218
TI  - Bayesian analysis and model selection for interval-censored survival data.
AB  - Interval-censored data occur in survival analysis when the survival time of each
      patient is only known to be within an interval and these censoring intervals
      differ from patient to patient. For such data, we present some Bayesian
      discretized semiparametric models, incorporating proportional and nonproportional
      hazards structures, along with associated statistical analyses and tools for
      model selection using sampling-based methods. The scope of these methodologies is
      illustrated through a reanalysis of a breast cancer data set (Finkelstein, 1986,
      Biometrics 42, 845-854) to test whether the effect of covariate on survival
      changes over time.

PMID- 11318219
TI  - Monte Carlo EM for missing covariates in parametric regression models.
AB  - We propose a method for estimating parameters for general parametric regression
      models with an arbitrary number of missing covariates. We allow any pattern of
      missing data and assume that the missing data mechanism is ignorable throughout.
      When the missing covariates are categorical, a useful technique for obtaining
      parameter estimates is the EM algorithm by the method of weights proposed in
      Ibrahim (1990, Journal of the American Statistical Association 85, 765-769). We
      extend this method to continuous or mixed categorical and continuous covariates,
      and for arbitrary parametric regression models, by adapting a Monte Carlo version
      of the EM algorithm as discussed by Wei and Tanner (1990, Journal of the American
      Statistical Association 85, 699-704). In addition, we discuss the Gibbs sampler
      for sampling from the conditional distribution of the missing covariates given
      the observed data and show that the appropriate complete conditionals are log
      concave. The log-concavity property of the conditional distributions will
      facilitate a straightforward implementation of the Gibbs sampler via the adaptive
      rejection algorithm of Gilks and Wild (1992, Applied Statistics 41, 337-348). We
      assume the model for the response given the covariates is an arbitrary parametric
      regression model, such as a generalized linear model, a parametric survival
      model, or a nonlinear model. We model the marginal distribution of the covariates
      as a product of one-dimensional conditional distributions. This allows us a great
      deal of flexibility in modeling the distribution of the covariates and reduces
      the number of nuisance parameters that are introduced in the E-step. We present
      examples involving both simulated and real data.

PMID- 11318220
TI  - On logit confidence intervals for the odds ratio with small samples.
AB  - Unless the true association is very strong, simple large-sample confidence
      intervals for the odds ratio based on the delta method perform well even for
      small samples. Such intervals include the Woolf logit interval and the related
      Gart interval based on adding .5 before computing the log odds ratio estimate and
      its standard error. The Gart interval smooths the observed counts toward the
      model of equiprobability, but one obtains better coverage probabilities by
      smoothing toward the independence model and by extending the interval in the
      appropriate direction when a cell count is zero.

PMID- 11318221
TI  - Bayesian monitoring of event rates with censored data.
AB  - A Bayesian approach to monitoring event rates with censored data is proposed. A
      Dirichlet prior for discrete time event probabilities is blended with discrete
      survival times to provide a posterior distribution that is a mixture of
      Dirichlets. Approximation of the posterior distribution via data augmentation is
      discussed. Practical issues involved in implementing the procedure are discussed
      and illustrated with a simulation of the single arm Cord Blood Transplantation
      Study where 6-month survival is monitored.

PMID- 11318222
TI  - Analysis of multistage pooling studies of biological specimens for estimating
      disease incidence and prevalence.
AB  - The testing of pooled samples of biological specimens for the purpose of
      estimating disease prevalence may be more cost effective than testing individual
      samples, particularly if the prevalence of disease is low. Multistage pooling
      studies involve testing pools and then sequentially subdividing and testing the
      positive pools. A simple estimator of disease prevalence and its variance are
      derived for general multistage pooling studies and are shown to be natural
      generalizations of Thompson's (1962) original estimators for single-stage pooling
      studies. The reduction in variance associated with each additional stage is
      calibrated. The results are extended to estimating disease incidence rates. The
      methods are used to estimate HIV incidence rates from a prevalence study of early
      HIV infection using a PCR assay for HIV RNA.

PMID- 11318223
TI  - SIMEX variance component tests in generalized linear mixed measurement error
      models.
AB  - In the analysis of clustered data with covariates measured with error, a problem
      of common interest is to test for correlation within clusters and heterogeneity
      across clusters. We examined this problem in the framework of generalized linear
      mixed measurement error models. We propose using the simulation extrapolation
      (SIMEX) method to construct a score test for the null hypothesis that all
      variance components are zero. A key feature of this SIMEX score test is that no
      assumptions need to be made regarding the distributions of the random effects and
      the unobserved covariates. We illustrate this test by analyzing Framingham heart
      disease data and evaluate its performance by simulation. We also propose
      individual SIMEX score tests for testing the variance components separately. Both
      tests can be easily implemented using existing statistical software.

PMID- 11318224
TI  - Exact tests of goodness of fit of log-linear models for rates.
AB  - We propose Metropolis-Hastings sampling methods for estimating the exact
      conditional p-value for tests of goodness of fit of log-linear models for
      mortality rates and standardized mortality ratios. We focus on two-way tables,
      where the required conditional distribution is a multivariate noncentral
      hypergeometric distribution with known noncentrality parameter. Two examples are
      presented: a 2 x 3 table, where the exact results, obtained by enumeration, are
      available for comparison, and a 9 x 7 table, where Monte Carlo methods provide
      the only feasible approach for exact inference.

PMID- 11318225
TI  - Mixed effects models with censored data with application to HIV RNA levels.
AB  - Mixed effects models are often used for estimating fixed effects and variance
      components in longitudinal studies of continuous data. When the outcome being
      modelled is a laboratory measurement, however, it may be subject to lower and
      upper detection limits (i.e., censoring). In this paper, the usual EM estimation
      procedure for mixed effects models is modified to account for left and/or right
      censoring.

PMID- 11318226
TI  - Statistical issues in a metaregression analysis of randomized trials: impact on
      the dietary sodium intake and blood pressure relationship.
AB  - In a meta-analysis of randomized trials of the effects of dietary sodium
      interventions on blood pressure, we found substantial heterogeneity among the
      studies. We were interested in evaluating whether measurement error, known to be
      a problem for dietary sodium measures, publication bias, or confounding factors
      could be responsible for the heterogeneity. A measurement error correction was
      developed that corrects both the slope and the intercept and takes into account
      the sample size of each study and the number of measurements taken on an
      individual. The measurement error correction had a minimal effect on the
      estimates, although it performed well in simulated data. A smoothed scatter plot
      was used to assess publication bias. Metaregressions provide a convenient way to
      jointly assess the effects of several factors, but care must be taken to fit an
      appropriate model.

PMID- 11318227
TI  - Multivariate survival analysis with positive stable frailties.
AB  - In this paper, we describe Bayesian modeling of dependent multivariate survival
      data using positive stable frailty distributions. A flexible baseline hazard
      formulation using a piecewise exponential model with a correlated prior process
      is used. The estimation of the stable law parameter together with the parameters
      of the (conditional) proportional hazards model is facilitated by a modified
      Gibbs sampling procedure. The methodology is illustrated on kidney infection data
      (McGilchrist and Aisbett, 1991).

PMID- 11318228
TI  - Comparison of several independent population means when their samples contain log
      normal and possibly zero observations.
AB  - In this paper, we consider the problem of testing the mean equality of several
      independent populations that contain log-normal and possibly zero observations.
      We first showed that the currently used methods in statistical practice,
      including the nonparametric Kruskal-Wallis test, the standard ANOVA F-test and
      its two modified versions, the Welch test and the Brown-Forsythe test, could have
      poor Type I error control. Then we propose a likelihood ratio test that is shown
      to have much better Type I error control than the existing methods. Finally, we
      analyze two real data sets that motivated our study using the proposed test.

PMID- 11318229
TI  - Predictive margins with survey data.
AB  - In the analysis of covariance, the display of adjusted treatment means allows one
      to compare mean (treatment) group outcomes controlling for different covariate
      distributions in the groups. Predictive margins are a generalization of adjusted
      treatment means to nonlinear models. The predictive margin for group r represents
      the average predicted response if everyone in the sample had been in group r.
      This paper discusses the use of predictive margins with complex survey data,
      where an important consideration is the choice of covariate distribution used to
      standardize the predictive margin. It is suggested that the textbook formula for
      the standard error of an adjusted treatment mean from the analysis of covariance
      may be inappropriate for applications involving survey data. Applications are
      given using data from the 1992 National Health Interview Survey (NHIS) and the
      Epidemiologic Followup Study to the first National Health and Nutrition
      Examination Survey (NHANES I).

PMID- 11318230
TI  - Memory in coal tits: an alternative model.
AB  - Jolliffe and Jolliffe (1997, Biometrics 53, 1136-1142) proposed various models
      for data from an experiment on memory in coal tits. This article describes an
      alternative model, which fits equally well and which may be simpler to interpret.

PMID- 11318231
TI  - Modelling ties in the sign test.
AB  - If ties occur in the sign test, the procedure recommended by Coakley and Heise
      (1996, Biometrics 52, 1242-1251) is the asymptotic uniformly most powerful
      nonrandomised test due to Putter (1955, Annals of Mathematical Statistics 26, 368
      386). It may be shown that this is a consequence of how the probability of a tie
      is modelled. Other models with different optimal procedures can be constructed.

PMID- 11318232
TI  - The relationship between zinc and copper status and lipid levels in African
      Americans.
AB  - Studies examining the role of zinc and copper nutriture as risk factors for
      cardiovascular disease in European Americans have produced conflicting results.
      This study assessed the associations between zinc and copper status and serum
      lipid levels in an adult African-American community. A cross-sectional study was
      conducted on 600 individuals (233 males, 367 females) from 25 to 65 yr of age
      using a random sampling design in a small city in Alabama. Anthropometric,
      dietary, and serum zinc, copper, and lipid measurements were made. The mean serum
      zinc and copper levels and dietary zinc intake were similar to that reported
      previously for European Americans. There were no significant associations between
      serum zinc, copper, or zinc/copper ratio and total serum cholesterol, high
      density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL
      C), or triglyceride levels. For males, there was a small but significant
      association between dietary zinc and the total cholesterol/HDL-C ratio (r = 
      0.17, p = 0.03). Similarly, females taking either zinc supplements or a
      multivitamin including zinc had higher HDL-C values than nonsupplementing
      females. Further prospective studies of the relationship between zinc status and
      lipid levels in African Americans are needed to verify these results.

PMID- 11318233
TI  - Zinc inhibits the mixed lymphocyte culture.
AB  - The mixed lymphocyte culture (MLC) is an established clinical method for bone
      marrow transplantation, as it serves as an in vitro model for allogenic reaction
      and transplantation. We previously showed that cytokine release into the
      supernatant is a more specific and sensitive parameter for cross-reactivity in
      the MLC than the common measurement of cell proliferation. Therefore we tried to
      find an inhibitor of the MLC in vitro with the least side effects in vivo,
      measuring interferon (IFN)-gamma as one of the most important cytokines in
      posttransplant medicine. Earlier studies showed that zinc is an important trace
      element for immune function with both stimulatory and inhibitory effects on
      immune cells. We found that slightly elevated zinc concentrations (three to four
      times the physiological level), which do not decrease T-cell proliferation in
      vitro nor produce immunosuppressive effects in vivo, suppress alloreactivity in
      the mixed lymphocyte culture. In this report we analyzed the mechanism whereby
      zinc influences the MLC to possibly find a nontoxic way of immunosuppression.

PMID- 11318234
TI  - Effects of resistance exercise on plasma, erythrocyte, and urine Zn.
AB  - Twelve healthy male volunteers performed two resistance exercise sessions: a
      moderate resistance (MR) exercise session and a heavy resistance (HR) exercise
      session. Blood was collected before exercise and 5 min, 30 min, and 24 h after
      exercise. Urine was collected for 24 h before and 24 h after exercise. Plasma
      zinc (Zn) was markedly increased both 5 min and 30 min after MR and HR exercise
      and was returned to control values the next day. Total blood cell (TBC) Zn was
      decreased 5 min after MR and HR exercise but was not significantly different than
      control values at 30 min or 24 h. The changes in plasma and TBC Zn after HR
      exercise were significantly greater than changes after MR exercise. The results
      of this study are the first to report changes in Zn after resistance exercise.
      These data agree with previous studies reporting increases in plasma Zn and
      decreases in erythrocyte Zn after strenuous running, treadmill, or cycle
      ergometry exercise; however, the magnitude of the changes reported in this study
      are considerable greater that changes reported these previous studies. These data
      support suggestions that increases in plasma Zn levels are the result of leakage
      from the muscles resulting from muscle damage.

PMID- 11318235
TI  - Selective accumulations of aluminum in five human arteries.
AB  - The aim of the present study was to determine variability of aluminum (Al)
      accumulation in human arteries and to observe the relationship between Al and
      five other elements (Ca, Fe, Mg, P, and Si) in the arteries. The Al contents in
      the thoracic aorta, basilar, coronary, femoral, and radial arteries of 26 human
      subjects were estimated by an inductively coupled plasma-atomic emission
      spectrometer and compared quantitatively to five elements. Al was detected in 88%
      of the cases in both the femoral and radial arteries, 73% in the coronary artery,
      58% in the aorta, and 31% in the basilar artery. The average Al content was
      highest in the femoral artery (48.3 +/- 15.0 microg/g dry weight) and lowest in
      the basilar artery (8.1 +/- 3.6 microg/g). The Al had positive correlations with
      P, Ca, or Mg in both the aorta and femoral artery, and with Ca or P in the
      basilar artery. In the coronary artery, a correlation was found between Al and
      Si. No relationships were found between Al and each of the five elements in the
      radial artery. From these results, Al varied widely among the five arteries and
      accumulated more in the femoral and radial arteries but less in the basilar
      artery. These accumulations of Al were positively correlated with Ca or P in
      several arteries, but not sufficiently to explain the accumulation of Al. Further
      investigations are required to understand the mechanism of the variability of Al
      accumulation in the arteries.

PMID- 11318236
TI  - Prevention of axial elongation in myopia by the trace element zinc.
AB  - The effect of the trace element zinc on the change in the axial length and
      diopters and the variations of activities of superoxide dismutase (SOD) and
      nitric oxide synthase (NOS), and the content of NO in the retino pigmental
      epithelium choroid homogenate of the myopic eyes in form-sense-deprived chicks
      were studied. The results show that zinc can inhibit the elongation of axis oculi
      and increase the diopters in myopia. Meanwhile, the activities of SOD and NOS and
      the content of NO are significantly increased compared with the model group,
      indicating that zinc can be used to prevent and treat myopia to a certain extent.

PMID- 11318237
TI  - Electrolyte changes in plasma and urine of athletes during acute and rigorous bed
      rest and ambulatory conditions.
AB  - Rigorous bed rest (RBR) induces significant electrolyte changes, but little it is
      not known about the effect of acute bed rest (ABR) (i.e., abrupt confinement to a
      RBR). The aim of this study was to measure urinary and plasma electrolyte changes
      during ABR and RBR conditions. The studies were done during 3 d of a pre-bed-rest
      (BR) period and during 7 d of an ABR and RBR period. Thirty male trained athletes
      aged, 24.4 +/- 6.6 yr were chosen as subjects. They were divided equally into
      three groups: unrestricted ambulatory control subjects (UACS), acute-bed-rested
      subjects (ABRS), and rigorous-bed-rested subjects (RBRS). The UACS group
      experienced no changes in professional training and daily activities. The ABRS
      were submitted abruptly to a RBR regimen and without having any prior knowledge
      of the exact date and time when they would be subjected to an RBR regimen. The
      RBRS were subjected to an RBR regime on a predetermined date and time known to
      them from the beginning of the study. Sodium (Na), potassium (K), magnesium (Mg),
      calcium (Ca), and phosphate (P) in plasma and urine, plasma renin activity (PRA)
      and plasma aldosterone (PA), physical characteristics, peak oxygen uptake, and
      food and water intakes were measured. Urinary Na, K, Ca, Mg, and P excretion and
      plasma Na, K, Mg, Ca, and P concentration, PRA, and PA concentration increased
      significantly (p < or = 0.01), whereas body weight, peak oxygen uptake, and food
      and water intakes decreased significantly in the ABRS and RBRS groups when
      compared with the UACS group. However, urinary and plasma Na, K, Mg, P, and Ca,
      PRA, and PA values increased much faster and were much greater in the ABRS group
      than in the RBRS group. Plasma and urinary Na, K, Ca, Mg, and P, PRA and PA
      levels, food and water intakes, body weight, and peak oxygen uptake did not
      change significantly in the UACS group when compared with its baseline control
      values. It was shown that RBR and ABR conditions induce significant increases in
      urinary and plasma electrolytes; however, urinary and plasma electrolyte changes
      appeared much faster and were much greater in the ABRS group than the RBRS group.
      It was concluded that the more abruptly motor activity is ended, the faster and
      the greater the urinary and plasma electrolyte change.

PMID- 11318238
TI  - Effects of oral aluminum on essential trace elements metabolism during pregnancy.
AB  - The present study was conducted to assess in rats the effects of oral aluminum
      (Al) exposure on calcium (Ca), magnesium (Mg), manganese (Mn), copper (Cu), zinc
      (Zn), and iron (Fe) accumulation and urinary excretion. Three groups of plug
      positive Sprague-Dawley (SD) rats were given by gavage 0, 200, and 400 mg/kg/d of
      Al(OH)3 on gestational days 1-20. Three groups of nonpregnant female SD rats of
      the same age received Al(OH)3 by gavage at the same doses for 20 consecutive
      days. At the end of the treatment period, 24-h urine samples were collected for
      analysis of Al and essential elements. Subsequently, all animals were sacrificed
      and samples of liver, bone, spleen, kidneys, and brain were removed for metal
      analyses. With some exceptions, the urinary amounts of Al, Mn, and Cu excreted by
      pregnant animals as well as the urinary levels of Al excreted by nonpregnant rats
      were higher in the Al-treated groups than in the respective control groups.
      Although higher Al levels were found in the liver of pregnant rats, the
      concentrations of Al in the brain of these animals were lower than those found in
      the same tissues of nonpregnant rats. With regard to the essential elements,
      tissue accumulation was most affected in pregnant than in nonpregnant animals. In
      pregnant rats, the hepatic and renal concentrations of Ca, Mg, Mn, Cu, Zn, and
      Fe, as well as the levels of Ca in bone, and the concentrations of Cu in brain
      were significantly higher in the Al-exposed groups than in the control group.
      According to the current results, oral Al exposure during pregnancy can produce
      significant changes in the tissue distribution of a number of essential elements.

PMID- 11318239
TI  - Comparison of antioxidative and chelating effects of daidzein and daidzin on
      protein oxidative modification by copper in vitro.
AB  - Daidzein and its glycoside daidzin are isoflavones. Their antioxidative effects
      were compared in vitro. Although both compounds inhibited protein oxidative
      modification by copper, the inhibitory effect of daidzein was stronger than that
      of daidzin. Because daidzein showed a greater affinity for Cu2+, the antioxidant
      effect of these isoflavones may be dependent on their respective copper-chelating
      abilities.

PMID- 11318240
TI  - Motivational interviews as goal assessment for persons with psychiatric
      disability.
AB  - A necessary first step in the psychosocial treatment of persons with severe
      mental illness is helping them identify their goals. Unfortunately, goal
      assessment is often viewed as a categorical process in which individuals list
      needs for which they require services. Motivational interviews provide a more
      sophisticated approach in which persons specify the costs and benefits to each of
      the needs in the list. Benefits define the reasons why a person should pursue a
      goal; costs define barriers to achieving that goal. The basic mechanisms for
      understanding and implementing motivational interviews are summarized. Ways to
      circumvent barriers to motivational interviews are also discussed.

PMID- 11318241
TI  - Outcomes of a randomized small-group HIV prevention intervention trial for people
      with serious mental illness.
AB  - HIV prevalence is alarmingly high among persons with serious mental illness and
      severely mentally ill adults frequently engage in high-risk behavior practices.
      This study evaluated the effectiveness of a small-group HIV risk reduction
      intervention offered to 189 men and women in outpatient programs for severely
      mentally ill adults. Participants screened for HIV risk were randomly assigned to
      attend either a 7-session small-group cognitive-behavioral HIV risk reduction
      intervention or a time-matched comparison intervention and were followed at 3
      month intervals for one year. Participants who attended the HIV risk reduction
      intervention increased their condom use, had a higher percentage of intercourse
      occasions protected by condoms, and held more positive attitudes toward condoms.
      Women showed greater response to the intervention than men. While many behavior
      change effects were present at 3-, 6- and 9-month followup assessments, most
      diminished by the 12-month followup. These results under-score the need for
      tailored but ongoing HIV prevention efforts integrated into community programs
      that serve people with serious mental illness.

PMID- 11318242
TI  - Symptom severity and personal functioning among patients with schizophrenia
      discharged from long-term hospital care into the community.
AB  - Twenty recently deinstitutionalized residents of a 24-hour staffed community
      residential unit were assessed using measures of symptoms and functioning on two
      occasions one year apart. Overall inter-clinician agreements in ratings were
      good, but clinicians agreed more in their ratings of positive than of negative
      symptoms of schizophrenia. Levels of symptoms (measured with the Positive and
      Negative Syndrome Scale) and functioning (measured with the Multnomah Community
      Ability Scale) were similar to those of comparable groups of patients, and were
      moderately related, sharing approximately 50% of variance. For the whole group,
      mean measures of symptoms and functioning were generally unchanged at one year,
      with retest measures of symptoms more stable than measures of functioning.

PMID- 11318243
TI  - A test of the reliability and validity of the Multnomah Community Ability Scale.
AB  - Previous research shows that the Multnomah Community Ability Scale (MCAS) total
      score is reliable and has predictive validity. This study evaluates the MCAS
      total and sub-scale scores on a sample of 1,250 outpatient mental health clients
      in Washington State. The MCAS sub-scales are reliable, and there is evidence for
      their concurrent validity. However, the factor structure of the MCAS only
      partially replicated the hypothesized sub-scales, and the authors recommend that
      sub-scales as currently constructed not be used as performance indicators. If
      only the total MCAS is of interest to users, the authors recommend using the
      single-item SOFAS rather than the 17-item MCAS.

PMID- 11318244
TI  - Ward atmosphere, client satisfaction, and client motivation in a psychiatric work
      rehabilitation unit.
AB  - This study investigated the ward atmosphere of a psychiatric work rehabilitation
      unit and its relationships to clients' satisfaction with the unit and client
      motivation, operationalised as proneness to set personal goals for their
      rehabilitation. The Community-oriented Programs Environment Scale was used and 52
      clients participated. Their report of the ward atmosphere was in accordance with
      recommended levels on 5 sub-scales out of 10. A regression analysis revealed that
      optimal levels of order-and-organization and support were of importance for
      satisfaction with the unit. An optimal level of support was associated with a
      high rating of personal goals. This study added two therapeutically interesting
      factors-satisfaction and motivation-to the flora of factors that have been
      related to perceptions of the ward atmosphere.

PMID- 11318245
TI  - Effects of family interventions on burden of relatives of psychiatric patients in
      The Netherlands: a pilot study.
AB  - In this study, the effects of psychoeducational family support groups in the
      Netherlands on relatives' burden were investigated, using a quasi-experimental
      design. The experimental group consisted of 119 participants of 19 family support
      groups, the control group of 45 relatives of once-only informational meetings.
      Subjects from both groups filled in a questionnaire before the group started and
      one year later. While controlling for confounding variables in multiple
      regression analyses, significant effects of family support groups were found on
      elements of burnout and burden.

PMID- 11318246
TI  - Assessments, interventions, and outcomes: who cares? Introduction.

PMID- 11318247
TI  - Assessing readiness for change among persons with severe mental illness.
AB  - Studies focusing on the readiness of persons to change have burgeoned in recent
      years. Assessing readiness for change is viewed as important for interventions
      aimed at promoting health behaviors, such as smoking cessation and substance
      abuse programs. This study is the first to examine readiness for change, as
      conceived by Prochaska and his colleagues, among a sample of persons with severe
      mental illness who were about to participate in a vocational rehabilitation
      program. We examined the reliability, validity, and other psychometric properties
      of the Change Assessment Scale and its ability to predict attrition and actual
      change.

PMID- 11318248
TI  - Prevalence and risk factors for herpes simplex virus type 2 infection among
      middle-age women in Brazil and the Philippines.
AB  - BACKGROUND: Data comparing type-specific herpes simplex virus type 2 (HSV-2)
      seroprevalence and risk factors between comparable populations are largely
      unavailable, particularly from less-developed countries. GOAL: To examine the
      seroprevalence of HSV-2 infection and the risk factors for this infection among
      women in Sao Paulo, Brazil, and Manila, the Philippines. STUDY DESIGN:
      Altogether, 552 middle-aged women participating as control subjects in two
      cervical cancer studies were screened for type-specific HSV-2 antibodies.
      RESULTS: Herpes simplex virus type 2 seroprevalence was higher in Brazil (42%)
      than in the Philippines (9.2%). The mean ages of Brazilian (n = 181) and Filipino
      (n = 371) women were 52.4 and 46.6 years, respectively. Brazilian participants
      had more lifetime sexual partners, less education, and more often a husband with
      other sexual partners than Filipino women. Herpes simplex virus type 2 was
      independently associated with younger age at first intercourse in both countries.
      More than one lifetime sexual partner, a husband with other sexual partners,
      urban/semi-urban residence, and no history of condom use were HSV-2 risk factors
      in Brazil, but not in the Philippines, where long-term hormonal contraceptive use
      was associated with increased risk. CONCLUSIONS: The higher HSV-2 seroprevalence
      in Brazil than in the Philippines may be explained largely by differences in the
      sexual behavior of women and their husbands. Herpes simplex virus type 2
      seroprevalence data may be used as a marker of past sexual behavior for the
      direct comparison of different population groups.

PMID- 11318249
TI  - Prevalence of Mobiluncus spp among women with and without bacterial vaginosis as
      detected by polymerase chain reaction.
AB  - BACKGROUND: Mobiluncus spp are highly associated with bacterial vaginosis, but
      their role in its pathogenesis is unknown. The authors used polymerase chain
      reaction (PCR) to compare the prevalence of Mobiluncus in women with and without
      bacterial vaginosis. GOAL: To compare the prevalence of Mobiluncus spp among
      women with and without bacterial vaginosis and to compare the sensitivities of
      PCR and Gram stain for detection. STUDY DESIGN: Vaginal specimens from 74 women
      were analyzed by PCR and Gram stain for the presence of Mobiluncus spp.
      Comparisons were made between the prevalence of this organism between the two
      cohorts and between the Gram stain and PCR detection methods. RESULTS: Mobiluncus
      was detected by PCR in 84.5% of women with bacterial vaginosis and in 38% of
      women without infection. M curtisii was rarely detected in the latter group,
      though it was found in 65.3% of women with bacterial vaginosis. The sensitivity
      and specificity of Gram stain compared with PCR were 46.9% and 100%,
      respectively. CONCLUSIONS: Mobiluncus is more common in healthy women than
      previously suspected, with M mulieris as the predominant species. The significant
      difference in the prevalence of M curtisii between women with bacterial vaginosis
      and uninfected women suggests that this species could be involved in the
      pathogenesis of bacterial vaginosis.

PMID- 11318250
TI  - Sampling individuals with large sexual networks: an evaluation of four
      approaches.
AB  - BACKGROUND: Methods for accessing large sexual networks are essential for
      investigating the mechanisms for the spread of sexually transmitted infections.
      GOAL: Four samples of cases were compared with the total population to determine
      which identified the largest networks. STUDY DESIGN: Individuals with positive
      test results for chlamydia during a 6-month period were selected from a
      laboratory database and linked with sex partner information from a notifiable
      disease registry. Sexual networks were constructed for a random sample, people
      with positive results from two or more tests for chlamydia, people with positive
      tests results for both gonorrhea and chlamydia, and the preceding two groups
      combined. RESULTS: The coinfected people combined with the repeaters yielded the
      highest proportion (47.8%) of large networks (>10 people), followed by the
      coinfected people, the repeaters, and finally the random sample. CONCLUSIONS:
      People coinfected with chlamydia and gonorrhea and those with repeated chlamydial
      infection present ideal opportunities for both research and prevention.

PMID- 11318251
TI  - Psychosocial correlates of adolescents' worry about STD versus HIV infection:
      similarities and differences.
AB  - BACKGROUND: Adolescents' worry (perceived threat) of sexually transmitted
      diseases (STDs) and HIV infection may have different correlates. This study
      examined associations between selected psychosocial and behavioral constructs and
      adolescents' worry about STD and HIV infection. GOAL: To assess levels and
      correlates of worry about STD and HIV among a high-risk sample of black
      adolescent females. STUDY DESIGN: High-risk black females (n = 522), enrolled in
      a randomized, controlled HIV and STD prevention trial, completed a questionnaire
      and structured interview at baseline. Worry about STD and HIV infection, recent
      risk behaviors, and several measures potentially related to worry were assessed.
      RESULTS: Levels of worry for both STD and HIV were low. Recent history of STD
      infection was associated with STD worry (OR, 4.6) and HIV worry (OR, 2.0).
      Infrequent communication about sex (OR, 2.0) and low perceived ability to
      negotiate condom use (OR, 2.0) were related to STD worry; whereas, only partner
      specific barriers were related to HIV worry (OR, 1.9). CONCLUSIONS: Despite high
      risk, adolescents were generally complacent about the threat of infection with
      STD and HIV. Adolescents' worry about STD and HIV infection had different sets of
      correlates.

PMID- 11318252
TI  - Dynamics of male circumcision practices in northwest Tanzania.
AB  - BACKGROUND: Male circumcision status is considered an important cofactor in the
      spread of HIV and sexually transmitted disease. There is limited evidence that
      male circumcision practices in Africa may be changing. GOAL: To assess the
      determinants of male circumcision status in a traditionally noncircumcising
      ethnic group and to investigate the reasons for increasing acceptance of
      circumcision. METHODS: Data from a factory workers study and a rural cohort study
      in northwest Tanzania were used to analyze the levels and determinants of male
      circumcision status and assess the reliability of self-reported data. Qualitative
      data from focus group discussions and in-depth interviews were obtained to
      ascertain norms and values in relation to male circumcision. RESULTS: Male
      circumcision has become more popular in recent years, and 21% of 3,491 men
      reported themselves as circumcised. An increase in circumcision rates was
      observed in the rural cohort study during 1994 to 1997, though reporting
      inconsistencies are common. Circumcision rates were higher among men with higher
      levels of education and in Muslim men. Men are often circumcised in their late
      teens or twenties. The reasons for the increasing popularity of circumcision were
      investigated in group discussions and in-depth interviews. The most frequently
      mentioned reason was health-related; circumcision was thought to enhance penile
      hygiene, reduce sexually transmitted disease incidence, and improve sexually
      transmitted disease cure rates. CONCLUSION: Male circumcision is becoming more
      popular among a traditionally noncircumcising ethnic group in Tanzania,
      especially in urban areas and among boys who have attended secondary schools.

PMID- 11318253
TI  - Urine-based screening for Chlamydia trachomatis in men attending sexually
      transmitted disease clinics.
AB  - BACKGROUND: Nucleic acid-amplified tests for Chlamydia trachomatis are accurate
      but costly. Screening strategies for asymptomatic men are needed. GOAL: To assess
      C trachomatis screening strategies for asymptomatic males. STUDY DESIGN: Men
      attending a sexually transmitted disease clinic were tested for C trachomatis
      with ligase chain reaction and culture, and for urethral inflammation with urine
      leukocyte esterase and urethral Gram stain. RESULTS: C trachomatis prevalence was
      5.5% among 1,625 asymptomatic men. Ligase chain reaction increased detection by
      49% among men without urethral inflammation. An age of younger than 25 years and
      urethral inflammation were associated with positive ligase chain reaction
      results. The negative predictive value of urine leukocyte esterase was highest
      among older men, but urethral Gram stain was equally sensitive in predicting
      infection regardless of age. An age of younger than 30 years or urethral
      inflammation identified the highest proportion of infections (92%) and reduced
      the percentage of men screened by 43%. CONCLUSIONS: Urine ligase chain reaction
      increased C trachomatis detection, particularly among men without urethral
      inflammation. Testing all asymptomatic men younger than 30 years is optimal,
      whereas negative urine leukocyte esterase or urethral Gram stain results in men
      30 years or older support no testing.

PMID- 11318255
TI  - Management of urethritis in health maintenance organization members receiving
      care at a multispecialty group practice in Massachusetts.
AB  - BACKGROUND: Cost containment has led to a concern that health maintenance
      organization-insured patients presenting with complaints of urethritis may be
      treated without being tested. GOAL: To determine the proportion of men presenting
      with symptoms of urethritis who are tested for Chlamydia trachomatis and
      Neisseria gonorrhoeae. STUDY DESIGN: Reviews were performed on 196 randomly
      selected patient records with an outpatient visit and a diagnostic code
      consistent with urethritis between 1995 and 1997. Data were collected on
      demographics, diagnostic testing, and treatment. RESULTS: Diagnostic testing for
      C trachomatis and N gonorrhoeae was performed, respectively, in 92.3% and 83.2%
      of the men presenting at an initial visit with complaints of urethritis.
      Altogether, 98.2% of the patients who met the Centers for Disease Control
      criteria for documenting urethritis were tested for C trachomatis and N
      gonorrhoeae. CONCLUSION: Diagnostic testing for C trachomatis and N gonorrhoeae
      is nearly universal in this multispecialty group practice setting, facilitating
      surveillance and public health efforts.

PMID- 11318254
TI  - Treatment of external genital warts in men using 5% imiquimod cream applied three
      times a week, once daily, twice daily, or three times a day.
AB  - BACKGROUND: Medical therapy for genital warts remains suboptimal. The topical
      interferon and cytokine inducer, imiquimod, has been proved effective for the
      treatment of external genital and perianal warts, but there is a substantial
      difference in the response rates between men and women. When 5% imiquimod cream
      is applied three times a week up to 16 weeks, approximately two thirds of women
      treated with imiquimod achieve complete clearance of genital warts, whereas only
      about one third of men clear completely. GOAL: This study was undertaken to
      determine whether more frequent application of topical imiquimod cream would
      improve the rate of genital wart clearance in men. STUDY DESIGN: A randomized
      treatment trial involving adult men with biopsy-proven genital warts was
      conducted at nine centers in the United States and Canada using four different
      application frequencies. RESULTS: Complete clearance rates during the 16-week
      treatment period were as follows for the different imiquimod treatment
      frequencies: three times a week (35 %), once daily (28 %), twice daily (24%), and
      three times a day (27%)(P = 0.88). The four treatment groups all showed
      comparable reductions in the total lesion area, with a median of more than a 90%
      reduction in the lesion area by the end of treatment. There was a significant
      increase in the incidence and severity of local skin reactions including
      erythema, vesicle formation, ulceration, and excoriation as the dosing frequency
      increased from three times a week to three times a day. CONCLUSIONS: In this
      study, the optimal dosage regimen was the approved three times a week regimen.
      More frequent application (up to three times a day) did not improve clearance and
      was associated with an increase in local adverse events.

PMID- 11318256
TI  - Socioeconomic status and self-reported gonorrhea among African American female
      adolescents.
AB  - BACKGROUND: Socioeconomic status is often used to explain race differences in
      sexually transmitted diseases (STDs), yet the independent association of
      socioeconomic status and STDs among adolescents has been understudied. OBJECTIVE:
      To examine the associations between socioeconomic status and self-reported
      gonorrhea among black female adolescents, after controlling for sexual risk
      behaviors. METHODS: Interviews and surveys were completed by 522 sexually active
      black adolescent females residing in low-income urban neighborhoods. RESULTS:
      Adolescents whose parents were unemployed were more than twice as likely to
      report a history of gonorrhea, compared with those with employed parents.
      Adolescents living with two parents were less likely to report a history of
      gonorrhea. CONCLUSIONS: The results of this study indicate that gonorrhea is
      associated with low socioeconomic status among black adolescent females
      regardless of the level of sexual risk behaviors. Lower socioeconomic status may
      be an marker for risky sociosexual environments.

PMID- 11318258
TI  - The use of between-methods triangulation in cancer nursing research: a case study
      examining information sources for partners of women with breast cancer.
AB  - This article describes between-methods triangulation-the combination of research
      strategies using different methods--and illustrates its use in cancer nursing
      research by outlining a case study, which identified the information sources for
      partners of women with breast cancer. By combining both qualitative and
      quantitative data, the study was found to possess good convergent validity.
      Between-methods triangulation also provided a more complete picture of the topic
      of inquiry than that supplied by either method alone. It is a useful strategy for
      identifying the information sources for partners of women with breast cancer and
      its use is encouraged in cancer nursing research.

PMID- 11318257
TI  - Douching and endometritis: results from the PID evaluation and clinical health
      (PEACH) study.
AB  - BACKGROUND: Douching has been related to risk of pelvic inflammatory disease
      (PID). GOAL: To examine the association between douching and PID in a large,
      multicenter, clinical trial of PID after adjustment for race/ethnicity. STUDY
      DESIGN: Interviews were conducted with 654 women who had signs and symptoms of
      PID. Vaginal Gram stains and upper genital tract pathology/cultures were obtained
      from all the women. Women with evidence of plasma cell endometritis and/or
      gonococcal or chlamydial upper genital tract infections were compared with women
      who had neither endometritis nor upper genital tract infection. RESULTS: Women
      with endometritis or upper genital tract infection were more likely to have
      douched more than once a month or within 6 days of enrollment than women who
      never douched. These associations remained after adjustment for confounding
      factors, after analysis of black women only; and among women with normal or
      intermediate vaginal flora but not bacterial vaginosis. CONCLUSION: Among a
      predominantly black group of women with clinical PID, frequent and recent
      douching was associated with endometritis and upper genital tract infection.

PMID- 11318259
TI  - Educating nurses to care for the dying in Hong Kong: a problem-based learning
      approach.
AB  - Caring for dying patients is an essential and major aspect of nursing care.
      However, previous studies have revealed that nurses felt uncomfortable and
      inadequate in dealing with the dying patients and their families. This study
      reports the effectiveness of a problem-based learning approach in death education
      among a group of registered nurses in Hong Kong. Three problems, with three
      segmented scenarios related to cancer nursing, were used. Students went through
      the problem-based learning process and documented their learning throughout the
      course in journals. A total of 72 sets of journals were collected and analyzed.
      The strategies of within case and cross-case analysis were employed. The within
      case analysis explored the learning development of students for each problem. The
      cross-case analysis compared and contrasted findings of the within case analysis.
      Three themes have been derived from the findings. They were: nurses acknowledging
      their emotions in facing death and dying, a need for the nurses to be better
      equipped in communication and counseling, and a holistic and family-centered
      approach to care. This study provides evidence showing that problem-based
      learning is an effective strategy to enhance nurses' self-awareness of death and
      dying issues, and to stimulate nurses to formulate a plan that addresses the
      physical, psychological, and social aspects of care. Findings also reveal that
      nurses need to take into account the particular reactions of death and dying in
      the Chinese culture when planning care.

PMID- 11318261
TI  - Cancer care in Nepal: variables that affect diagnosis, treatment, and prognosis:
      a case study.
AB  - This manuscript presents a case study of a Nepalese woman experiencing breast
      cancer. Six themes were identified to have an impact on the diagnosis, treatment,
      and prognosis. They include: cultural impact on women's roles, socioeconomic
      status and education, surgical oncologist-patient relationship, surgical
      oncologist-nurse relationship, nurses' lack of oncology knowledge, and lack of a
      cancer screening and prevention program in Nepal. Cancer care is on the rise in
      Nepal. However, many of the variables identified above are not considered in the
      cancer care provided. Nepal has just opened its first national cancer center with
      the intent to improve cancer care throughout the country.

PMID- 11318260
TI  - End-of-life decision making by adolescents, parents, and healthcare providers in
      pediatric oncology: research to evidence-based practice guidelines.
AB  - Participating in end-of-life decisions is life altering for adolescents with
      incurable cancer, their families, and their healthcare providers. However, no
      empirically developed and validated guidelines to assist patients, parents, and
      healthcare providers in making these decisions exist. The purpose of the work
      reported here was to use three sources (the findings of three studies on decision
      making in pediatric oncology, published literature, and recommendations from
      professional associations) to develop guidelines for end-of-life decision making
      in pediatric oncology. The study designs include a retrospective, descriptive
      design (Study 1); a prospective, descriptive design (Study 2); and a cross
      sectional, descriptive design (Study 3). Settings for the pediatric oncology
      studies included a pediatric catastrophic illness research hospital located in
      the Midsouth (Studies 1 and 2); and that setting plus a children's hospital in
      Australia and one in Hong Kong (Study 3). Study samples included 39 guardians and
      21 healthcare providers (Study 1); 52 parents, 10 adolescents, and 22 physicians
      (Study 2); and 43 parents (Study 3). All participants in the studies responded to
      six open-ended questions. A semantic content analysis technique was used to
      analyze all interview data. Four nurses independently coded each interview;
      interrater reliability per code ranged from 68% to 100% across studies. The most
      frequently reported influencing factors were "information on the health and
      disease status of the patient," "all curative options having been attempted,"
      "trusting the healthcare team," and "feeling support from the healthcare
      provider." The agreement across studies regarding influencing factors provides
      the basis for the research-based guidelines for end-of-life decision making in
      pediatric oncology. The guidelines offer assistance with end-of-life decision
      making in a structured manner that can be formally evaluated and individualized
      to meet patient and family needs.

PMID- 11318262
TI  - Anxiety, coping strategies, and coping behaviors in patients undergoing head and
      neck cancer surgery.
AB  - BACKGROUND: Little is reported in the scientific literature about the modulating
      effect of anxiety on the coping process before and after surgical treatment for
      head and neck cancer. OBJECTIVES: The major purpose of this article is to
      describe the relationships among preoperative anxiety and use of coping
      strategies, and postoperative self-care and resocialization behaviors in patients
      who sustain facial disfigurement/dysfunction with head and neck cancer surgery.
      METHODS: Using a prospective descriptive design, 75 (N = 75) adults who were
      about to sustain facial disfigurement and dysfunction associated with head and
      neck cancer surgery were entered into the study. The State Trait Anxiety
      Inventory and the Ways of Coping Questionnaire were administered to the
      respondents. The Disfigurement/Dysfunction Scale and Coping Behaviors Score
      values were calculated by the investigator. RESULTS: Self-care and anxiety were
      significantly correlated on postoperative day 4 (r = 2.30; p < .05) and on
      postoperative day 5 (r = 2.35; p < .05). For the 3 days under study, the
      relationship between total self-care and anxiety became stronger on postoperative
      day 5 (r = 2.39; p < .01), indicating that self-care on postoperative day 4 is
      related to reduced anxiety on postoperative day 5. In other words, self-care
      appears to precede reduction in anxiety in this sample. Secondly, there was a
      negative relationship between self-care and anxiety that increased over the early
      postoperative period. CONCLUSIONS: This study prospectively documents anxiety in
      surgical head and neck cancer patients. The findings suggest that at a specific
      point in time (postoperative day 5), self-care precedes reduction in anxiety, and
      that this negative relationship increases over time. Additional investigation is
      now critical in order to describe long-term recovery after surgical treatment for
      head and neck cancer and to develop appropriate interventions to meet the unique
      needs of this population.

PMID- 11318263
TI  - Alterations in taste sensation: a case presentation of a patient with end-stage
      pancreatic cancer.
AB  - Alterations in taste can occur as a result of cancer, cancer treatment, and from
      a variety of other causes. Cancer patients frequently experience taste
      alterations, which often go undetected in the clinical setting. This case
      presentation depicts a 90-year-old client with end-stage pancreatic cancer
      undergoing chemotherapy treatment with gemcitabine. The symptomatology of taste
      changes is described. Etiology and rationale for taste changes is presented for
      the cancer patient population, and for the general population. Review of the
      cancer literature, research instruments, and goals/outcomes are discussed. The
      author determined that interventional studies are lacking, and research is
      needed.

PMID- 11318264
TI  - Development of a breast self-examination program for the Internet: health
      information for Korean women.
AB  - Internet-based health information will enable us to interact with many people
      despite distance and time constraints. Informational media by computer is
      expected to become an important factor that affects health behavior. This study
      was done to develop an accessible multimedia program about breast self
      examination on the Internet. This study was designed by using the two steps of
      need assessment and program development. For the need assessment step, a survey
      was carried out. The sample consisted of the 82 women of Yonsei University
      selected by convenient random sampling. At the program development step, screen
      design took into account perspectives of computer engineering. A storyboard for
      every screen was made via screen design and then ported to computer using the
      Netscape Navigator program. A breast self-examination program was developed using
      Netscape 4.0 on the Windows 98 platform. The multimedia program, including text,
      graphics, animation, and sound, was constructed with HTML language using Memo
      Sheet in Netscape Navigator. The contents of health information posted on the
      Internet included general information about breast cancer, the importance of
      breast self-examination, self-risk appraisal of breast cancer, the diverse
      methods about breast self-examination, the monthly check list graph, and social
      network for consultation. It is possible to interact with clients through the
      Question and Answer function on screen. This Internet-based health information
      program provides enough information, which can be accessed using search systems
      on the Internet.

PMID- 11318265
TI  - Research into practice: the foundation for evidence-based care.

PMID- 11318266
TI  - Priorities for adult cancer nursing research: a West Australian replication.
AB  - Two Delphi surveys have been conducted during the past 20 years to identify
      cancer nursing research priorities; one in the United States and one in Canada.
      Sir Charles Gairdner Hospital, the State Cancer Referral Centre in Western
      Australia, undertook a replication of this Delphi survey to identify nursing
      research priorities for adult cancer nursing. The aim of this replication was to
      identify possible changes in priorities and account for cultural difference in
      the healthcare systems. A total of 45 responses were received from the first
      Delphi round and 30 from the second. The top ten priorities identified by this
      sample were different from those identified in prior studies. The top ranked
      research topic was "What strategies would be most helpful in allowing nurses time
      to provide emotional support to cancer patients and carers?" These results may
      stimulate discussion and re-assessment of research priorities in other adult
      cancer care settings.

PMID- 11318267
TI  - Diffusion of pain management research into nursing practice.
AB  - The promotion of evidence based practice is a challenge within nursing. Pain
      management is a prime example of this practice research gap. There is solid
      evidence for 20 years to promote positive change in our methods of pain
      management, yet outdated approaches are still amazingly evident. Even among
      oncology nurses, who place a high value on promoting patient comfort, there is a
      lack of evidence-based pain management. Rogers' Diffusion of Innovation Theory
      provides an interesting framework for examining the issues and possible solutions
      to this complex problem. Rogers' theory examines how changes diffuse through a
      social system over time and also exposes some of the barriers and facilitators to
      this process. The theory looks at adopters, the nature of the innovation, the
      social system, and communication patterns. Identifying the barriers of the past
      will help nursing to overcome these same barriers and increase the adoption of
      evidence-based pain management approaches in the future.

PMID- 11318268
TI  - The National Screening Committee review of diabetic retinopathy screening.

PMID- 11318269
TI  - Malignant solitary fibrous tumour of the orbit: report of a case with 8 years
      follow-up.

PMID- 11318270
TI  - Eccentric disciform lesions: a marker of treponemal disease?

PMID- 11318271
TI  - Late-onset capsular block syndrome: an occult cause of decreased vision in a 63
      year-old pseudophakic Asian woman.

PMID- 11318272
TI  - Sphenoid sinus mucocoele mimicking aneurysmal oculomotor nerve palsy.

PMID- 11318273
TI  - Ipsilateral proliferative diabetic retinopathy in carotid stenosis.

PMID- 11318274
TI  - Corneal perforation in chronic graft-versus-host disease.

PMID- 11318275
TI  - Sporadic Burkitt's lymphoma presenting as solely orbital disease in a 78-year
      old.

PMID- 11318276
TI  - Watery eye: a new side-effect of isotretinoin therapy.

PMID- 11318277
TI  - Proteus syndrome: a variant with eye involvement.

PMID- 11318278
TI  - Bilateral sixth nerve palsy treated with augmented vertical muscle transposition.

PMID- 11318279
TI  - Cystoid macular oedema in uveitis: an unsolved problem.
AB  - Most papers on the subject of CMO associated with uveitis are retrospective,
      combine patients with different disease aetiologies, at different stages of
      evolution, and often describe patients who were previous treatment failures with
      other therapies besides the one under consideration. There are almost no
      prospective randomised double-masked controlled studies. This is perhaps in part
      due to the relative sparsity of uveitis patients seen by many uveitis centres. At
      the moment, treatment is largely empirical, based in large part on the studies,
      and others, quoted above. The need to regularly repeat courses of therapy, loss
      of efficacy of certain form of therapy after repeated use, and cumulative side
      effects, all need to be taken into consideration when interpreting results and
      deciding upon the best approach to be adopted. The risks to the patient's well
      being increase with the addition of systemic medication, and long-term steroid
      use can cause hypertension, induce or exacerbate diabetes, cause premature
      osteoporosis, cushingoid features, peptic ulceration and aseptic necrosis of the
      femoral head. Immunosuppressive drugs can be nephrotoxic, hepatotoxic, cause
      hypertension, gastric disturbances and excessive hair growth. The assessment of
      macular changes, both structurally and functionally, is the key aspect in
      understanding visual loss in CMO and also in predicting potential visualrecovery.
      The combined use of the various tools mentioned here, such as SLO, OCT and
      electrodiagnostic tests, may give us some of the necessary answers in this
      process. However, all these tests will need to be validated. A prospective
      analysis of CMO in cases of uveitis, especially if coupled with therapeutic
      intervention, will give us the opportunity to achieve this objective.

PMID- 11318280
TI  - The cosmetic improvement of ocular deformities with spectacles.

PMID- 11318281
TI  - Massive subretinal haemorrhage associated with central serous chorioretinopathy.

PMID- 11318282
TI  - Burns to the face from ignition of an eye pad.

PMID- 11318283
TI  - Solitary fibrous tumour of the orbit.

PMID- 11318284
TI  - Corneal autografts.

PMID- 11318286
TI  - Resetting the intraocular pressure.

PMID- 11318285
TI  - Diabetic retinopathy screening.

PMID- 11318287
TI  - Active management in patients with ocular manifestations of myasthenia gravis.
AB  - PURPOSE: Myasthenia gravis can cause variable strabismus with disabling diplopia
      and/or poor cosmesis. A retrospective study of a group of patients with
      myasthenia gravis or 'myasthenia gravis like' syndromes was made. METHODS: The
      study group consisted of patients who had undergone botulinum toxin treatment
      and/or surgery for disabling diplopia, poor cosmesis or both. Surgical treatment
      was by conventional techniques including recess/resect, posterior fixation,
      superior oblique tenotomy and adjustable sutures. RESULTS: There were 9 patients
      in the study group (8 female, 1 male). Age at surgery ranged from 21 to 59 years
      (mean 46 years). Six were symptom-free following treatment. Two, although
      symptomatically improved, had occasional diplopia. One patient failed treatment
      and required an occlusive contact lens. CONCLUSIONS: The ocular manifestations of
      myasthenia gravis or 'myasthenia gravis like' syndromes may respond to surgery
      and/or botulinum toxin injection. Active intervention should be considered when
      deviations become stable. To our knowledge this is the first report of the use of
      botulinum toxin in such patients.

PMID- 11318288
TI  - Value of high-frequency ultrasound biomicroscopy in uveitis.
AB  - PURPOSE: To determine the use of high-frequency ultrasound biomicroscopy (UBM) in
      the assessment of inflammatory lesions of the iris, ciliary body, pars plana and
      peripheral vitreous, and in particular to determine the proportion of cases for
      which UBM contributed significant additional, hitherto inaccessible, information.
      METHODS: Charts of patients seen in the uveitis clinic at University Eye Hospital
      from November 1994 to September 1999 for whom a UBM investigation had been
      performed were analysed. UBM was performed in a standard manner, using a Humphrey
      UBM 840 system. The clinical relevance of the UBM findings was determined for the
      whole series and for the following six subgroups of patients arbitrarily
      established according to the type and location of pathology: hypotony,
      pseudophakic uveitis, iris and ciliary body pathology excluding hypotony, pars
      plana pathology, scleritis and Toxocara uveitis. Findings were classified as
      positive when they confirmed a suspected diagnosis of lesional process or when
      they gave essential information. Findings were classified as essential when they
      led to the diagnosis or when they modified therapeutic intervention. RESULTS:
      During the study period 111 eyes of 77 patients were included. UBM findings
      contributed essential information that allowed a diagnosis to be reached or that
      influenced treatment in 43% of cases. It yielded positive findings in 91% of
      cases, enabling assessment of morphological changes in the iris, ciliary body,
      and retroiridal and peripheral vitreous induced by intraocular inflammatory or
      pseudo-inflammatory disorders. Specific UBM signs, present in all patients, were
      identified in Toxocara uveitis. The groups of patients that benefited most from
      UBM examination were those with hypotony (83% essential findings) and opaque
      media (100% essential findings). CONCLUSION: For uveitis patients with an
      inflammatory process situated in the iris/ciliary body/pars plana/retroiridal
      vitreous areas, UBM was of great clinical value and improved the management in a
      significant manner.

PMID- 11318289
TI  - Mechanistic considerations when contemplating a diagnosis of non-accidental
      injury in an infant with vitreous haemorrhage and retinopathy of prematurity.
      Comment on: Kwok et al. Can vitreous haemorrhage indicate non-accidental injury
      if mild retinopathy of prematurity is present? Eye 2000; 14:812-3.

PMID- 11318290
TI  - Characteristics and outcomes of paediatric rhegmatogenous retinal detachment
      treated by segmental scleral buckling plus an encircling element.
AB  - PURPOSE: To evaluate the outcome of paediatric rhegmatogenous retinal detachment
      treated by segmental scleral buckling plus an encircling element. METHODS: A
      retrospective review was carried out of 15 consecutive paediatric patients (16
      eyes). RESULTS: Thirteen of the 15 patients were male (87%), 2 (13%) were female.
      Their average age was 10.9 years (range 6-18 years; median 10 years). Retinal
      detachment was caused by trauma in 9 of 16 eyes (56%), high myopia in 5 of 16
      eyes (31%) and had an unknown cause in 2 of 16 eyes (13%). Diagnosis was delayed
      by more than 1 month in 10 of 16 eyes (63%). The visual acuity was 6/60 or worse
      and the macula was detached on presentation in 13 of 16 eyes (81%). Two of 16
      eyes (13%) had mild proliferative vitreoretinopathy. Final reattachment was
      achieved in all cases. Of 11 eyes with a follow-up of 6 months or more, there was
      improvement in visual acuity in 7 (63%), and a best-corrected visual acuity of
      6/20 or better in 5 (46%). CONCLUSION: Paediatric rhegmatogenous retinal
      detachment is characterised by a delay in diagnosis and a high degree of macular
      involvement on presentation. Anatomical reattachment with segmental scleral
      buckling plus an encircling element was successful in all eyes, and improvement
      of visual acuity was achieved in one-half of the eyes which had a follow-up of 6
      months or more.

PMID- 11318291
TI  - Ischaemic heart disease may predispose to pseudophakic cystoid macular oedema.
AB  - PURPOSE: Pseudophakic macular oedema (PMO) is uncommon following uncomplicated
      phacoemulsification and lens implantation and the cause of infrequent cases is
      rarely understood. This study was undertaken to determine whether a relationship
      exists between ischaemic heart disease (IHD) and PMO. METHODS: Retrospective case
      note review was carried out of 177 (252 eyes) consecutive patients without pre
      existing retinal disease who underwent phacoemulsification and intraocular lens
      implantation during a 12 month period. Patients with a post-operative best
      corrected visual acuity < 6/9 underwent slit-lamp biomicroscopy and fluorescein
      angiography to identify PMO. IHD was defined on clinical and electrocardiographic
      grounds. The incidence of IHD was compared in patients with and without PMO and
      statistical analysis performed using the Fisher's exact test. RESULTS: PMO
      occurred in 4 patients (6 eyes), all of whom had IHD, whereas no PMO occurred in
      the remaining 173 patients (246 eyes) (p = 0.04). CONCLUSIONS: Pseudophakic
      macular oedema represents an important complication following modern
      phacoemulsification and intraocular lens implantation and is associated
      significantly with ischaemic heart disease.

PMID- 11318292
TI  - Topical cyclosporin A in the management of vernal keratoconjunctivitis.
AB  - PURPOSE: To study the efficacy of topical cyclosporin A in children with vernal
      keratoconjunctivitis in a prospective randomised double-masked trial. METHODS:
      Twenty-four children between 5 and 16 years of age were randomly treated with
      cyclosporin A (CsA) and placebo (vehicle) and followed up for 4 months. RESULTS:
      Of the 12 patients given CsA, 11 showed symptomatic improvement by 7 days of
      starting treatment whereas only 3 patients in the placebo group showed mild
      symptomatic improvement. CONCLUSIONS: Topical cyclosporin is a safe and effective
      treatment in vernal keratoconjunctivitis.

PMID- 11318293
TI  - Traumatic wound dehiscence following cataract surgery: a thing of the past?
AB  - PURPOSE: This study compares the frequencies of traumatic wound dehiscence
      following extracapsular cataract extraction (ECCE) and following
      phacoemulsification through a self-sealing corneoscleral tunnel. METHODS: A
      retrospective review was performed of the surgical record at a British eye
      hospital from September 1986 to August 1993 and January 1996 to December 1998.
      Cases requiring surgical repair of wound dehiscence following cataract extraction
      were identified. The frequencies of traumatic wound dehiscence following ECCE and
      phacoemulsification were compared using a two by two contingency table (chi
      square test). RESULTS: Twenty-one cases of traumatic wound dehiscence were
      identified following 5,600 ECCEs (0.4%). In 4,200 phacoemulsification procedures
      only one case of traumatic wound dehiscence was identified (0.02%) (p = 0.0006,
      OR 15.8, chi2 = 11.69). CONCLUSION: Phacoemulsification through a self-sealing
      corneoscleral tunnel is associated with significantly less risk of traumatic
      wound dehiscence than is extracapsular cataract extraction. The case of wound
      rupture following phacoemulsification is discussed with reference to a mechanism
      for the injury.

PMID- 11318294
TI  - Non-enhanced trabeculectomy by non-glaucoma specialists: are results related to
      risk factors for failure?
AB  - PURPOSE: To determine the 1 year success rate of non-enhanced trabeculectomy
      under the care of non-glaucoma specialists and the effects of risk factors on the
      surgical outcome as measured by intraocular pressure (IOP) control. METHODS: A
      retrospective study of 167 patients undergoing trabeculectomy was performed. One
      hundred and four cases were performed in a teaching hospital and 63 in a district
      general hospital (DGH). Non-glaucoma specialists performed all the operations,
      enhanced trabeculectomy with antimetabolites being excluded. Information was
      recorded from a retrospective review of case notes, and post-operative IOPs at 12
      months follow-up were analysed. Risk factors for failure were defined as: (1) age
      less than 40 years old, (2) black race, (3) diabetes mellitus, (4) miotic therapy
      > or = 18 months, (5) sympathomimetic therapy > or = 6 months, (6) pseudophakia
      or aphakia, (7) previous failed filtration procedure, (8) argon laser
      trabeculoplasty, (9) previous ocular surgery and (10) high-risk glaucoma (angle
      recession glaucoma, uveitic glaucoma and neovascular glaucoma). A success was
      defined to be a post-operative IOP at 1 year of less than 21 mmHg and at least
      20% less than the presenting IOP on no medication. RESULTS: The overall success
      rate was 139 of 167 (83.2%). Eighty-seven of 104 eyes (83.7%) were classified as
      a success in the teaching hospital group and 52 of 63 (82.5%) were classified as
      a success in the DGH group. There was no significant difference in the number of
      risk factors between the success and failure groups. Eyes with two or more risk
      factors had significantly higher IOPs at 1 year when compared with eyes with 0 or
      1 risk factor (mean +/- SD: 17.4 +/- 6.34 mmHg vs 14.2 +/- 5.0 mmHg, p = 0.022).
      When only 'successful eyes' were analysed, those with two or more risk factors
      still had significantly higher IOPs at 1 year (mean +/- SD: 15.0 +/- 3.0 mmHg vs
      12.8 +/- 3.9 mmHg, p = 0.046). There were significantly fewer eyes in the two or
      more risk factor group with IOPs < 16 mmHg at 1 year (26.1% vs 60.4%, p = 0.021).
      CONCLUSIONS: Eyes at relatively low risk for failure operated upon by non
      glaucoma specialists appeared to have success rates similar to previously
      published series. Eyes with two or more risk factors for failure have higher IOPs
      at 1 year in non-enchanced trabeculectomy. Adjunctive anti-scarring agents may be
      considered for these patients when filtration surgery is scheduled.

PMID- 11318295
TI  - Inverse Knapp procedure.

PMID- 11318296
TI  - New Tonopen XL: comparison with the Goldmann tonometer.
AB  - PURPOSE: To compare the intraocular pressure (IOP) values obtained using a
      Goldmann tonometer (Haag-Streit) with those obtained with the new Tonopen XL
      (Mentor), which has certain differences compared with first- and second
      generation models. METHODS: The IOPs of 104 patients were assessed by Goldmann
      tonometer and Tonopen XL tonometer. Goldmann measurements was done first in 145
      eyes and Tonopen measurements were done first in 53 eyes. Four observers measured
      the IOP. Observers A, B and C used the Goldmann tonometer first and then the
      Tonopen XL, while observer D used the Tonopen XL first and then the Goldmann
      tonometer. The results were analysed by descriptive analysis and, when the
      distribution of the data was normal, paired t-test and Pearson's r coefficient
      were used to compare and correlate IOP measurements between Goldmann and Tonopen
      measurements. When the distribution of the data was non-normal, the Wilcoxon
      matched-pair test and Spearman coefficient were used. The agreement between
      Goldmann and Tonopen values was also calculated. ANOVA test was used to compare
      the difference obtained by 'Goldmann minus Tonopen' measurements among the three
      different observers. RESULTS: A statistically significant difference (p < 0.0001)
      was found between the IOP readings obtained by Goldmann tonometer and the Tonopen
      XL and a significant correlation was found between the Goldmann values and
      Tonopen XL values (p < 0.001). When the Goldmann IOP was more than 20 mmHg the
      Tonopen XL measurements were lower than the Goldmann values. Also in this group
      this difference was statistically significant. No significant difference was
      found between Goldmann values and Tonopen values among the three observers, even
      though a significant difference was found between Goldmann values and Tonopen
      values for observer B. When the values obtained by first the Goldmann tonometer
      and then the Tonopen XL were compared with those obtained by first the Tonopen XL
      and then the Goldmann tonometer, no significant difference was found between the
      two groups. CONCLUSION: The new Tonopen XL provides similar results to the
      Goldmann tomometer in 62% of the cases and was slightly less accurate than the
      Goldmann tonometer for extreme values, just like the previous Tonopen.
      Nevertheless the precision is good enough for the purpose of adequate screening.

PMID- 11318297
TI  - Twenty-four hour intraocular pressure reduction with latanoprost compared with
      pilocarpine as third-line therapy in exfoliation glaucoma.
AB  - PURPOSE: To compare the 24 hour efficacy of latanoprost 0.005% given every
      evening with that of pilocarpine 4% given four times daily as third-line therapy
      in patients with exfoliation glaucoma receiving timolol 0.5% and dorzolamide 2%
      each given twice daily. METHOD: We enrolled 30 patients with exfoliation glaucoma
      not adequately controlled on timolol maleate 0.5% and dorzolamide 2%. Each
      patient underwent a baseline 24 hour intraocular pressure curve testing at 06:00,
      10:00, 14:00, 18:00, 22:00 and 02:00 hours. Patients were randomised to receive
      either latanoprost 0.005% or pilocarpine 4% for a minimum of 8 weeks and were
      then crossed over to the opposite therapy. Diurnal curve testing was repeated at
      the end of each treatment. RESULTS: There was a significant decrease from
      baseline in intraocular pressure at each timepoint for both study medicines (p <
      0.016). Latanoprost provided better intraocular pressure control than pilocarpine
      at daytime measuresments (17.4 vs 19.7 mmHg at 06:00 hours, p < 0.001; 17.8 vs
      19.1 mmHg at 10:00 hours, p = 0.04). However, pilocarpine reduced the pressure
      more than latanoprost at 22:00 hours (18.4 vs 19.5 mmHg, p = 0.016). Overall, the
      diurnal intraocular pressure was reduced from a baseline of 21.5 +/- 3.7 mmHg to
      18.8 +/- 3.1 mmHg on pilocarpine and to 18.0 +/- 3.0 mmHg on latanoprost (p =
      0.06). In addition, mean peak pressure was similar between pilocarpine (21.0 +/-
      2.9 mmHg) and latanoprost (20.5 +/- 3.8 mmHg) (p = 0.20). Side-effects were
      similar with the exception of blurred vision, which was only found with
      pilocarpine (10%). Compliance was more difficult with pilocarpine. CONCLUSION: In
      exfoliation glaucoma, as a third-line adjunctive therapy added to timolol and
      dorzolamide, latanoprost and pilocarpine have similar diurnal efficacy. However,
      latanoprost provides a greater morning pressure reduction.

PMID- 11318298
TI  - The acute effect of pilocarpine on pulsatile ocular blood flow in ocular
      hypertension.
AB  - PURPOSE: To determine the acute effects of application of 2% pilocarpine on
      pulsatile ocular blood flow. METHODS: In a randomised prospective controlled
      study of an exploratory nature, 18 subjects with ocular hypertension had
      pilocarpine 2% eye drops instilled into a randomly chosen eye three times at 10
      min intervals. Physiological saline was instilled into the contralateral control
      eye. Intraocular pressure (IOP) and pulsatile ocular blood flow (POBF)
      measurements were taken before the first application and 90 min after the last
      application using the OBF tonometer (OBF Laboratory, Wilts, UK). Statistical
      analysis was performed using the Wilcoxon signed rank test. RESULTS: Of the 18
      patients who entered the trial, 2 were suggested by the OBF system software as
      having 'poorly reliable' data. The analysis was made on the remaining 16. There
      was a significant reduction in IOP at 90 min for the treated eye in comparison
      with the contralateral control eye (p = 0.001; median difference -4.25 mmHg; 95%
      confidence interval, -5.85 to -2.40). There was a significant increase in POBF at
      90 min in the treated eye in comparison with the contralateral control eye (p <
      0.001; median difference 4.60 microl/s; 95% confidence interval, 2.35 to 6.75).
      CONCLUSION: Acute application of pilocarpine 2% drops increased POBF to a
      significant extent in untreated ocular hypertension.

PMID- 11318299
TI  - Balloon dacryocystoplasty study in the management of adult epiphora.
AB  - PURPOSE: To determine the efficacy of dacryocystoplasty with balloon dilation in
      the treatment of acquired obstruction of the nasolacrimal system in adults.
      METHODS: Balloon dacryocystoplasty was performed in 52 eyes of 42 patients under
      general anaesthetic. A Teflon-coated guidewire was introduced through the
      canaliculus and manipulated through the nasolacrimal system and out of the nasal
      aperture. A 4 mm wide 3 cm coronary angioplasty balloon catheter was threaded
      over the guidewire in a retrograde fashion and dilated at the site of
      obstruction. RESULTS: There was complete obstruction in 30% of cases and partial
      obstruction in 70%. The most common site of obstruction was the nasolacrimal
      duct. The procedure was technically successful in 94% of cases. The overall re
      obstruction rate was 29% within 1 year of the procedure. There was an anatomical
      failure rate of 17% for partial obstruction and 69% for complete obstruction
      within 1 year. CONCLUSIONS: Balloon dacryocystoplasty has a high recurrence rate.
      There may be a limited role for this procedure in partial obstructions. Further
      refinements of the procedure are necessary before it can be offered as a
      comparable alternative to a standard surgical dacryocystorhinostomy.

PMID- 11318300
TI  - Review of the inverse Knapp procedure: indications, effectiveness and results.
AB  - PURPOSE: To evaluate the indications and results of inverse Knapp procedures
      performed at one institution over a 10 year period between 1987 and 1996.
      METHODS: The records of patients who had undergone inverse Knapp procedures were
      retrospectively reviewed. Demographic data were collected, pre- and post
      operative orthoptic assessments were evaluated, and pre- and post-operative
      binocular single vision (BSV) charts and Hess charts were scored. RESULTS: Twenty
      one patients were identified and records were available in 17. The main
      indication for the operation was orbital trauma. The mean vertical deviation in
      primary position and downgaze improved from 16.06 prism dioptres (PD) to 7.35 PD
      and 26.45 PD to 6.66 PD respectively. The pre-operative average score for BSV was
      42%, increasing to 62% post-operatively. The Hess chart error scores improved on
      average from 848.8 pre-operatively to 296.4 post-operatively. Further operations
      were required for 8 patients. CONCLUSIONS: Inverse Knapp procedure is an uncommon
      strabismus operation but an extremely useful one in selected cases. We recommend
      it for the treatment of marked inferior rectus weakness, congenital or acquired,
      for post-traumatic inferior rectus underaction with or without orbital blow-out
      fracture and for residual large hypertropia in patients with poor binocular
      functions. The extent of inferior rectus underaction should be assessed very
      carefully to avoid overcorrecting.

PMID- 11318301
TI  - Associations of high myopia in childhood.
AB  - PURPOSE: High myopia in early childhood is a recognised association of ocular and
      systemic disease. The aim of this study was to describe the types, pattern and
      frequency of these associations. METHODS: All children presenting to two
      ophthalmology units over 3 years who were found to have high myopia were
      recruited. High myopia was defined as one or both eyes demonstrating 6 dioptres
      spherical equivalent or more of myopic refractive error on retinoscopy. We
      limited the age to less than 10 years old. A retrospective case review was
      undertaken of the 112 consecutive children who fulfilled the criteria above. The
      demographic data, source and indication for referral were recorded along with the
      ocular and systemic findings and diagnosis. RESULTS: Only 9 (8%) of the children
      had 'simple high myopia' with no associated ocular or systemic associations. In
      54% there was an underlying systemic association with or without further ocular
      problems (e.g. developmental delay, prematurity, Marfan, Stickler, Noonan, Down
      syndrome) and in the remaining 38% there were further ocular problems associated
      with the high myopia (e.g. lens subluxation, coloboma, retinal dystrophy,
      anisometropic amblyopia). A family history of high myopia did not preclude
      associated abnormality: in 4 cases the diagnosis of a systemic condition in the
      child led to the identification of the disease in at least one myopic relative.
      Asian (p < 0.001) and male (p < 0.05) patients were overrepresented in the
      series. CONCLUSION: High myopia is strongly associated with systemic and ocular
      problems; it may be the reason for the child's initial medical referral and an
      important clue to an underlying systemic or ocular condition. Referrals
      infrequently originated from community optometrists despite prior attendance. We
      suggest that all children under 10 years of age with high myopia are referred to
      a paediatric ophthalmology clinic for review and we propose a structured clinical
      evaluation in the hospital eye clinic.

PMID- 11318302
TI  - The epidemiology of ocular trauma in Singapore: perspective from the emergency
      service of a large tertiary hospital.
AB  - PURPOSE: To describe the epidemiology of ocular trauma from the perspective of
      the emergency service of a large tertiary hospital in Singapore. METHODS: A
      prospective survey was conducted over a 3 month period (August to October 1997)
      on all patients seen at the ophthalmic unit at the Singapore General Hospital's
      emergency service. Data on clinical presentation, type and cause of injury and
      use of eye protective devices (EPD) were collected via a standardised interview
      and examination. RESULTS: A total of 870 persons presented with a diagnosis of
      ocular trauma, out of the 1,631 patients seen during the study period. Compared
      with non-trauma cases, trauma cases were more likely to be male (odds ratio (OR):
      4.2, 95% confidence interval (95% CI): 3.2, 5.4), non-residents (OR: 6.2, 95% CI:
      3.7, 10.5), younger than 40 years of age (OR: 3.2, 95% CI: 2.7, 4.1) and less
      likely to require follow-up or hospital admission (OR: 0.2, 95% CI: 0.2, 0.3).
      The three most common types of injuries were superficial foreign body (58.2%),
      corneal abrasion (24.9%) and blunt trauma (12.6%), while open globe injury
      occurred in only 17 cases (2%). Comparison with a 10% random sample of all cases
      seen in the previous 9 months (n = 284) revealed no significant time variation in
      the types of injuries (p = 0.63). Work-related injuries accounted for 590 (71.4%)
      cases, where grinding, cutting metal and drilling were the specific activities in
      more than 90% of the cases. In appropriate settings, only 21.7% of patients with
      work-related injuries used EPD; 43.7% were provided with EPD, but did not use
      them at the time of injury; and the remaining 34.6% reported that EPD were not
      provided. CONCLUSIONS: Ocular trauma at the emergency service level in Singapore
      involved mainly young non-resident men, were work-related and associated with
      well-defined activities, and were generally minor. The low prevalence of EPD use
      reinforces the need for a review of the design and implementation of occupational
      eye safety programmes, especially among non-resident workers.

PMID- 11318303
TI  - Characterisation of epithelial cell line from rat cornea.
AB  - PURPOSE: Characterisation of RtCE-1 cells, newly established rat corneal
      epithelial cell line. METHODS: Morphology of RtCE-1 cells was characterised by
      light and electron microscopy. Expression of cytokeratins was studied by
      polyacrylamide electrophoresis and Western blotting. Characterisation of RtCE-1
      cells also included karyotype analysis and in vitro study of growth kinetics.
      RESULTS: The line shows morphological similarities to normal corneal epithelium.
      The cells express cornea-specific cytokeratins. Karyotype analysis revealed that
      the cells are polyploid with modal number of chromosomes at passage 30 equalling
      72 +/- 14. Growth of the line is partially dependent on EGF. CONCLUSION: RtCE-1
      cells may constitute a model for the evaluation of proliferation, function and
      differentiation of corneal epithelium in vitro.

PMID- 11318305
TI  - The opalescence of hydrogel intraocular lens.

PMID- 11318304
TI  - Presence and possible significance of immunohistochemically demonstrable
      metallothionein expression in pterygium versus pinguecula and normal conjunctiva.
AB  - PURPOSE: To investigate metallothionein (MT) expression in pterygium, pinguecula
      and normal conjunctiva and define its possible significance in this area of the
      eye. In order to further elucidate the mechanism of MT expression we correlated
      it with lymphocyte subpopulations (T4, T8), macrophages (CD68), Langerhans' cells
      (S100) and the proliferation-associated indices (PCNA, Ki67). METHODS: Eighty
      five surgically excised pterygia, 15 pingueculae and 20 normal conjunctivae were
      immunohistochemically studied by the avidin-biotin (ABC) method. A monoclonal
      antibody (E9) against a conserved epitope of I and II isoforms of MT was used on
      formalin-fixed, paraffin-embedded tissues. Statistical analysis was performed
      using the SPSS statistical package. RESULTS: Epithelial MT expression was
      detected in all 120 cases examined and in most of them both nuclear and
      cytoplasmic immunoreactivity was present. Nevertheless no statistically
      significant difference of MT expression was found between the three types of
      tissue. A statistically significant positive correlation between MT expression
      and lymphocyte subsets, macrophages and Langerhans' cells was found in pterygium.
      On the contrary, we did not find any statistical correlation in pinguecula and
      normal conjunctiva. In all three types of tissues MT expression was also
      positively correlated with the proliferation-associated indices. CONCLUSION: The
      data suggest that there is immunohistochemically demonstrable MT expression in
      the epithelium of pterygium, but also of normal conjunctiva and pinguecula. MT
      may serve a photoprotective role in this region. In pterygium in particular, the
      biochemical pathway of MT synthesis seems interestingly to cross the pathways of
      cell proliferation, inflammation and immune activation.

PMID- 11318306
TI  - Are elderly people being screened for visual impairment in general practice?

PMID- 11318307
TI  - Chorioretinal alterations in mucormycosis.

PMID- 11318308
TI  - The routine use of personal patient dosimeters is of little value in detecting
      therapeutic misadministrations.

PMID- 11318309
TI  - Determination of percentage depth-dose curves for electron beams using different
      types of detectors.
AB  - According to the new AAPM TG-51 dosimetry protocol, reference dosimetry for
      electron beams is performed at depth of d(ref)=0.6R50-0.1 (cm) instead of d(max)
      recommended in TG-21. In clinical practice most electron beams are normalized at
      d(max). Therefore it becomes more important to get an accurate percentage-depth
      dose (%dd) curve particularly for higher-energy electron beams in which the depth
      d(ref) is away from d(max). When ionization chambers are used in determining %dd
      curves the water-to-air stopping-power ratios and the fluence correction factors
      are required. The TG-51 recommends that the stopping-power ratios for realistic
      electron beams be used instead of the monoenergetic stopping-power ratios used in
      TG-21. This investigation aims to study the effects of those correction factors
      on the determination of %dd curves. We observed 1% deviations in the value of %dd
      at d(ref) for 15 and 18 MeV beams between a plane-parallel NACP and a cylindrical
      IC-10 chamber without considering the fluence correction factors P(fl). We
      explored a method to derive the fluence correction factors at any depth by using
      the existing fluence correction data at d(max) and tested its feasibility. We
      compared %dd curves measured by a diode detector and a NACP chamber with stopping
      power ratios recommended by TG-51 and those recommended by TG-21. We found that
      for 15 and 18 MeV beams the difference in the values of %dd at d(ref) between
      using those two different stopping-power ratios is about 0.5%. Excellent
      agreement is found between %dd curves measured by the diode and by the NACP
      chamber when the stopping-power ratios recommended by TG-51 are used.

PMID- 11318310
TI  - The properties of the ultramicrocylindrical ionization chamber for small field
      used in stereotactic radiosurgery.
AB  - Accurate dosimetry of small-field photon beams tends to be difficult to perform
      due to the presence of lateral electronic disequilibrium and steep dose
      gradients. In stereotactic radiosurgery (SRS), small fields of 6-30 mm in
      diameter are used. Generally thermoluminescence dosimetry chips, Farmer, Thimble
      ion chamber, and film dosimetry are not adequate to measure dose in SRS beams.
      These techniques generally do not provide the required precision due to their
      energy dependence and/or poor resolution. It is necessary to construct a small,
      accurate detector with high spatial resolution for the small fields used in SRS.
      The ultramicrocylindrical ionization chamber (UCIC) with a gold wall of 2.2 mm in
      diameter and 4.0 mm in length has dual sensitive volumes of air (8.0 mm3) and
      borosilicate (2.6 mm3) cavity. Reproducibility, linearity, and radiation damage
      with respect to absorbed dose, beam profile of small beam, and independence of
      dose rate of the UCIC are tested by the dose measurements in high energy photon
      (5, 15 MV) and electron (9 MeV) beams. The UCIC with a unique supporting system
      in the polystyrene phantom is demonstrated to be a suitable detector for the dose
      measurements in a small beam size.

PMID- 11318311
TI  - Accurate measurement of the dynamic response of a scanning electronic portal
      imaging device.
AB  - An important condition for the safe introduction of dynamic intensity modulated
      radiotherapy (IMRT) using a multileaf collimator (MLC) is the ability to verify
      the leaf trajectories. In order to verify IMRT using an electronic portal imaging
      device (EPID), the EPID response should be accurate and fast. Noninstantaneous
      dynamic response causes motion blurring. The aim of this study is to develop a
      measurement method to determine the magnitude of the geometrical error as a
      result of motion blurring for imagers with scanning readout. The response of a
      liquid-filled ionization chamber EPID, as an example of a scanning imager, on a
      moving beam is compared with the response of a diode placed at the surface of the
      EPID. The signals are compared under the assumption that all EPID rows measure
      the same dose rate when a straight moving field edge is imaged. The measurements
      are performed at several levels of attenuation to investigate the influence of
      dose rate on the response of the detector. The accuracy of the measurement method
      is better than 0.25 mm. We found that the liquid-filled ionization chamber EPID
      does not suffer from significant motion blurring under clinical circumstances.
      Using a maximum gradient edge detector to determine the field edge in an image
      obtained by a liquid-filled ionization chamber EPID, errors smaller than 1 mm are
      found at a dose rate of 105 MU/min and a field edge speed of 1.1 cm/s. The errors
      reduce at higher dose rates. The presented method is capable of quantifying the
      geometrical errors in determining the position of the edge of a moving field with
      subpixel accuracy. The errors in field edge position determined by a liquid
      filled ionization chamber EPID are negligible in clinical practice. Consequently,
      these EPIDs are suitable for geometric IMRT verification, as far as dynamic
      response is concerned.

PMID- 11318312
TI  - Intensity modulated proton therapy: a clinical example.
AB  - In this paper, we report on the clinical application of fully automated three
      dimensional intensity modulated proton therapy, as applied to a 34-year-old
      patient presenting with a thoracic chordoma. Due to the anatomically challenging
      position of the lesion, a three-field technique was adopted in which fields
      incident through the lungs and heart, as well as beams directed directly at the
      spinal cord, could be avoided. A homogeneous target dose and sparing of the
      spinal cord was achieved through field patching and computer optimization of the
      3D fluence of each field. Sensitivity of the resultant plan to delivery and
      calculational errors was determined through both the assessment of the potential
      effects of range and patient setup errors, and by the application of Monte Carlo
      dose calculation methods. Ionization chamber profile measurements and 2D
      dosimetry using a scintillator/CCD camera arrangement were performed to verify
      the calculated fields in water. Modeling of a 10% overshoot of proton range
      showed that the maximum dose to the spinal cord remained unchanged, but setup
      error analysis showed that dose homogeneity in the target volume could be
      sensitive to offsets in the AP direction. No significant difference between the
      MC and analytic dose calculations was found and the measured dosimetry for all
      fields was accurate to 3% for all measured points. Over the course of the
      treatment, a setup accuracy of +/-4 mm (2 s.d.) could be achieved, with a mean
      offset in the AP direction of 0.1 mm. Inhalation/exhalation CT scans indicated
      that organ motion in the region of the target volume was negligible. We conclude
      that 3D IMPT plans can be applied clinically and safely without modification to
      our existing delivery system. However, analysis of the calculated intensity
      matrices should be performed to assess the practicality, or otherwise, of the
      plan.

PMID- 11318313
TI  - Computer algebra for x-ray spectral reconstruction between 6 and 25 MV.
AB  - A previously presented algorithm for the reconstruction of bremsstrahlung spectra
      from transmission data has been implemented into MATHEMATICA. Spectra vectorial
      algebra has been used to solve the matrix system A * F = T. The new
      implementation has been tested by reconstructing photon spectra from transmission
      data acquired in narrow beam conditions, for nominal energies of 6, 15, and 25
      MV. The results were in excellent agreement with the original calculations. Our
      implementation has the advantage to be based on a well-tested mathematical
      kernel. Furthermore it offers a comfortable user interface.

PMID- 11318314
TI  - Estimate of absorbed dose based on two-dimensional autoradiographic information
      in internal radionuclide therapy.
AB  - In radiation therapies using radionuclides emitting short-range particles, such
      as radioimmunotherapy or boron neutron capture therapy, the biological effects
      are strongly affected by the heterogeneity of the absorbed dose distribution
      delivered to tumor cells. The three-dimensional (3D) information of the source
      distribution at the cellular level is required to accurately determine the
      absorbed dose distribution to the individual tumor cells. Two-dimensional
      distribution of cell and nuclide with a resolution of 1 microm can be obtained
      from individual tissue sections by microautoradiography. To obtain such
      information in 3D, an ideal approach would be to align the serial tissue sections
      from a block and analyze all of them. This is straightforward in theory, but
      extremely difficult in practice. Furthermore, every section in the block has to
      be processed and analyzed, and the usage of the data from this laborious work is
      very inefficient. An approach presented here is to estimate the absorbed dose
      based on individual sections without 3D reconstruction. It is realistically
      workable since it avoids the most difficult task of alignment for the serial
      tissue sections. In addition, the absorbed dose can be estimated based on a
      limited number of noncontiguous sections. The validity of this approach has been
      tested by a Monte Carlo simulation for two representative radionuclide
      configurations: (a) a uniform distribution of sources and (b) a cell membrane
      bound source distribution. With only a limited number of sampling sections, the
      uncertainties in the dose estimation were estimated to approximately 15% for
      short-range particles.

PMID- 11318315
TI  - The effect of seed anisotrophy on brachytherapy dose distributions using 125I and
      103Pd.
AB  - We have evaluated the effect of the anisotropy of individual seeds on dose
      distributions for permanent prostate implants using 125I and 103Pd. The dose
      distributions were calculated for various implants using both the line source and
      point source calculational formalisms, for two different models of 125I and 103Pd
      seeds. The dose distributions were compared using cumulative dose volume
      histograms (DVH) and cumulative difference dose volume histograms (deltaDVH) for
      the prostate target volume and for the rectum surface. The DVHs could not
      distinguish between the dose distributions from isotropic and non-isotropic
      seeds. However, the deltaDVHs were useful in determining the fraction of the
      target volume for which the difference between the dose distribution for line
      sources and for point sources exceeded a threshold value. The dose distributions
      were calculated (1) for all the seeds oriented co-linearly, along either the x-,
      y-, or z-axis, and (2) for the seeds at randomized orientations, more closely
      resembling the clinical situation. For all cases, there was a significant
      difference in the effect of seed anisotropy from the different seed types. For
      the geometrically simpler test cases with a small number of seeds, the effect of
      anisotropy on the dose distribution was too large to ignore for any of the seed
      types investigated. For the idealized pre-plan case, the effect was much smaller.
      For clinical prostate implants, the calculations done with seeds oriented co
      linearly along the z-axis (needle implant axis) were a reasonable approximation
      for those from simulations of seeds with randomized orientations. Again, the
      effect of anisotropy varied drastically between different seed models, and also
      between different clinical cases. However, the effect of anisotropy must be
      considered in the context of all the other uncertainties in clinical
      brachytherapy treatments.

PMID- 11318316
TI  - Temperature monitoring with line scan echo planar spectroscopic imaging.
AB  - A new magnetic resonance imaging method, line scan echo planar spectroscopic
      imaging (LSEPSI), is shown capable of providing rapid, internally referenced
      temperature monitoring from water and fat chemical shifts. METHODS: Orthogonal 90
      degrees and 180 degrees slice selective RF pulses inclined by 45 degrees from the
      image plane solicit a spin echo from a tissue column. The echo is read by
      asymmetric sampling of 32 gradient echoes spaced 1.4-1.8 ms apart. Sixty-four
      adjacent columns are sequentially sampled in 4.2-6.4 s with 4,096 voxels sampled
      with voxel volumes of 0.08-0.13 cm3. Mixed mayonnaise/water phantoms were used to
      correlate LSEPSI-derived chemical shifts and thermocouple-based temperature
      measurements from 23 to 60 degrees C with a 1.5 T scanner. Measurement artifacts
      unrelated to temperature were investigated with the phantom, as was the
      feasibility of applying the sequence in human breast in vivo. RESULTS: The
      correlation between LSEPSI and thermocouple-based temperature measurements in the
      phantom was excellent (r2>0.99). Field drifts affecting the temperature
      measurements using the water peak alone were corrected by using the water/lipid
      peak difference. The sequence had an average temperature resolution of 1.4
      degrees C in the phantom. The frequency difference measurement reduced the
      sensitivity to artifacts related to temperature. Both water and lipid peaks were
      detectable throughout many locations in the breast, suggesting the applicability
      of LSEPSI in this organ. DISCUSSION: T1-saturation losses occur in conventional
      and echo-planar based 2D CSI sequences using phase encoding methods with short TR
      periods. These losses are eliminated when individual columns are sampled in
      snapshot fashion with LSEPSI since the effective TR becomes the time between
      scans rather than excitations. T1 saturation can make small spectral peaks
      difficult to detect at high temperatures and generally lowers the signal-to-noise
      ratio of the spectra. The rapid acquisition and insensitivity to T1 saturation
      effects make LSEPSI an attractive technique for monitoring thermal therapies in
      breast using the internally referenced fat/water frequency separation.

PMID- 11318317
TI  - Determination of the presampled MTF in computed tomography.
AB  - A technique for measuring the presampled MTF in CT scanners is described. The
      technique uses a simple phantom consisting of approximately 0.050 mm aluminum
      foil sandwiched by flat plastic or tissue-equivalent slabs. The aluminum foil is
      slightly angled with respect to the reconstruction matrix, and CT images are
      acquired. The acquired CT image yields an angled slit image that can be used to
      synthesize the presampled line spread function (LSF). The presampled MTF is
      calculated from the presampled LSF. The technique is a direct extension of that
      proposed by Fujita et al. [IEEE Trans. Med. Imaging 11, 34-39 (1992)] for MTF
      calculation on digital radiography images. While the MTF in clinical CT scanners
      often reaches negligible amplitude below the Nyquist frequency, the technique is
      easy to implement, requires inexpensive materials, is robust to aliasing, and is
      more resilient to noise due to greater data averaging than conventional PSF
      integration techniques. Use of the proposed technique is illustrated on a
      clinical multiple detector array scanner, and MTFs are shown for several common
      reconstruction kernels. It is likely that the proposed technique would be useful
      for all tomographic imaging systems, including single photon emission computed
      tomography, positron emission tomography, magnetic resonance imaging and
      ultrasound scanners.

PMID- 11318318
TI  - Performance evaluation of computed radiography systems.
AB  - Recommended methods to test the performance of computed radiography (CR) digital
      radiographic systems have been recently developed by the AAPM Task Group No. 10.
      Included are tests for dark noise, uniformity, exposure response, laser beam
      function, spatial resolution, low-contrast resolution, spatial accuracy, erasure
      thoroughness, and throughput. The recommendations may be used for acceptance
      testing of new CR devices as well as routine performance evaluation checks of
      devices in clinical use. The purpose of this short communication is to provide a
      tabular summary of the tests recommended by the AAPM Task Group, delineate the
      technical aspects of the tests, suggest quantitative measures of the performance
      results, and recommend uniform quantitative criteria for the satisfactory
      performance of CR devices. The applicability of the acceptance criteria is
      verified by tests performed on CR systems in clinical use at five different
      institutions. This paper further clarifies the recommendations with respect to
      the beam filtration to be used for exposure calibration of the system, and the
      calibration of automatic exposure control systems.

PMID- 11318319
TI  - Filtered backprojection for modifying the impulse response of circular
      tomosynthesis.
AB  - A filtering technique has been developed to modify the three-dimensional impulse
      response of circular motion tomosynthesis to allow the generation of images whose
      appearance is like those of some other imaging geometries. In particular, this
      technique can reconstruct images with a blurring function which is more
      homogeneous for off-focal plane objects than that from circular tomosynthesis. In
      this paper, we describe the filtering process, and demonstrate the ability to
      alter the impulse response in circular motion tomosynthesis from a ring to a
      disk. This filtering may be desirable because the blurred out-of-plane objects
      appear less structured.

PMID- 11318320
TI  - Fourier-based approach to interpolation in single-slice helical computed
      tomography.
AB  - It has recently been shown that longitudinal aliasing can be a significant and
      detrimental presence in reconstructed single-slice helical computed tomography
      (CT) volumes. This aliasing arises because the directly measured data in helical
      CT are generally undersampled by a factor of at least 2 in the longitudinal
      direction and because the exploitation of the redundancy of fanbeam data acquired
      over 360 degrees to generate additional longitudinal samples does not
      automatically eliminate the aliasing. In this paper we demonstrate that for
      pitches near 1 or lower, the redundant fanbeam data, when used properly, can
      provide sufficient information to satisfy a generalized sampling theorem and thus
      to eliminate aliasing. We develop and evaluate a Fourier-based algorithm, called
      180FT, that accomplishes this. As background we present a second Fourier-based
      approach, called 360FT, that makes use only of the directly measured data. Both
      Fourier-based approaches exploit the fast Fourier transform and the Fourier shift
      theorem to generate from the helical projection data a set of fanbeam sinograms
      corresponding to equispaced transverse slices. Slice-by-slice reconstruction is
      then performed by use of two-dimensional fanbeam algorithms. The proposed
      approaches are compared to their counterparts based on the use of linear
      interpolation-the 360LI and 180LI approaches. The aliasing suppression property
      of the 180FT approach is a clear advantage of the approach and represents a step
      toward the desirable goal of achieving uniform longitudinal resolution properties
      in reconstructed helical CT volumes.

PMID- 11318321
TI  - Radiation doses to infants and adults undergoing head CT examinations.
AB  - For routine noncontrast CT examinations of the head, we compared the radiation
      doses of infant patients aged no more than two years old, with those of "adults"
      defined as any patient whose weight was greater than 40 kg. Data were obtained
      for 23 infants, and an equal number of "adults," who underwent CT head
      examinations between May 1997 and March 1998. Patient CT data acquired included
      the x-ray tube potential (kVp), mAs, section thickness, and total number of
      sections. For radiation dosimetry purposes, the head was modeled as a uniform
      cylinder of water using patient size data obtained from a representative cross
      sectional image. CT techniques and patient size data permitted the computation of
      the mean section doses in the head region, total energy imparted, and the
      corresponding effective doses. All CT scans were performed at 120 kVp, with an
      average current-exposure time product of 271 +/- 73 and 340 +/- 0 mAs for infants
      and "adults," respectively. The radius of the water cylinder used to model the
      patient head increased from 58 mm for 4 kg newborns to 70 mm for 8 kg infants.
      For "adults," there was little correlation between the weight of the patient and
      the mean water equivalent radius of 88 mm (r2 = 0.14). Mean section doses were
      44.4 +/- 11.1 mGy for infants, and 44.2 +/- 1.5 mGy for "adults." The energy
      imparted to infants correlated with patient weight (r2= 0.35) much more than did
      that of "adults" (r2= 0.02). The average infant energy imparted (66.4 +/- 28.7
      mJ) was approximately half the value obtained for "adults" (140 +/- 10 mJ). The
      average effective dose to the infants (7.6 +/- 3.1 mSv), however, was
      approximately six times higher than that for "adults" (1.3 +/- 0.1 mSv). There
      was no significant correlation between patient effective dose and patient mass
      for either the infant (r2 = 0.12) or the "adult" group of patients (r2= 0.02).
      Infant doses varied much more than "adult" doses, primarily because of a wider
      range of x-ray technique factors selected and secondarily due to the variation in
      infant head size. The observed variability in the computed radiation dose
      parameters indicates that it should be possible to reduce infant doses routinely
      in head CT examinations without any adverse effect on diagnostic imaging
      performance. For such routine head CT scans, the average dose reduction for
      infants weighing between 4 and 8 kg would be expected to range between 40% and
      60%.

PMID- 11318322
TI  - Comment on "Functional fitting of interstitial brachytherapy dosimetry data
      recommended by the AAPM Radiation Therapy Committee Task Group 43" [Med. Phys.
      26, 153-160 (1999)] and "Fitting and benchmarking of dosimetry data for new
      brachytherapy sources".

PMID- 11318324
TI  - Origin of deficits in the flicker electroretinogram of the cone system in X
      linked retinoschisis as derived from response nonlinearities.
AB  - The aim of this study was to identify the origin of a high-frequency attenuation
      in the flicker electroretinogram (ERG) of patients with X-linked retinoschisis
      (XLRS) through an analysis of nonlinearities in the ERG response. The ERGs of six
      patients with XLRS and six age-similar control subjects were recorded in response
      to stimuli that consisted of pairs of sinusoids that had varying temporal
      frequencies and that differed by either 8 or 16 Hz. Compared with the control
      subjects, the patients with XLRS showed a significant reduction in the amplitude
      of the difference frequency to high-frequency stimuli that paralleled the high
      frequency attenuation of their ERG response fundamental. This result indicates
      that a response attenuation at an initial linear filter, most likely
      photoreceptoral, was a major determinant of the reduced ERG amplitude of the XLRS
      patients at high temporal frequencies. Additional analyses of nonlinearities in
      the ERG responses provided evidence of a postreceptoral component to the flicker
      ERG deficits of the XLRS patients, as well.

PMID- 11318325
TI  - Light adaptation in motion direction judgments.
AB  - We examined the time course of light adaptation in the visual motion system.
      Subjects judged the direction of a two-frame apparent-motion display, with the
      two frames separated by a 50-ms interstimulus interval of the same mean
      luminance. The phase of the first frame was randomly determined on each trial.
      The grating presented in the second frame was phase shifted either leftward or
      rightward by pi/2 with respect to the grating in the first frame. At some
      variable point during the first frame, the mean luminance of the pattern
      increased or decreased by 1-3 log units. Mean luminance levels varied from
      scotopic or low mesopic to photopic levels. We found that the perceived direction
      of motion depended jointly on the luminance level of the first frame grating and
      the time at which the shift in average luminance occurs. When the average
      luminance increases from scotopic or mesopic to photopic levels at least 0.5 s
      before the offset of the first frame, motion in the 3pi/2 direction is perceived.
      When average luminance decreases to low mesopic or scotopic levels, motion in the
      pi/2 direction is perceived if the change occurs 1.0 s or more before first frame
      offset, depending on the size of the luminance step. Thus light adaptation in the
      visual motion system is essentially complete within 1 s. This suggests a rapid
      change in the shape (biphasic or monophasic) of the temporal impulse response
      functions that feed into a first-order motion mechanism.

PMID- 11318327
TI  - Three-dimensional transfer functions of coherent anti-Stokes Raman scattering
      microscopy.
AB  - The three-dimensional coherent transfer function of confocal coherent anti-Stokes
      Raman scattering microscopy was derived theoretically. The three-dimensional
      optical transfer function was also derived under the weak-contrast assumption.
      The effect of a pinhole in front of the detector on the optical transfer function
      was estimated, and it was found that the cutoff frequency of the optical transfer
      function is independent of the pinhole. Micrometer-order spatial resolution along
      the optical axis was also experimentally demonstrated.

PMID- 11318332
TI  - Recovery of optical parameters in multiple-layered diffusive media: theory and
      experiments.
AB  - Diffuse photon density waves have lately been used both to characterize diffusive
      media and to locate and characterize hidden objects, such as tumors, in soft
      tissue. In practice, most biological media of medical interest consist of various
      layers with different optical properties, such as the fat layer in the breast or
      the different layers present in the skin. Also, most experimental setups consist
      of a multilayered system, where the medium to be characterized (i.e., the
      patient's organ) is usually bounded by optically diffusive plates. Incorrect
      modeling of interfaces may induce errors comparable to the weak signals obtained
      from tumors embedded deep in highly heterogeneous tissue and lead to significant
      reconstruction artifacts. To provide a means to analyze the data acquired in
      these configurations, the basic expressions for the reflection and transmission
      coefficients for diffusive-diffusive and diffusive-nondiffusive interfaces are
      presented. A comparison is made between a diffusive slab and an ordinary
      dielectric slab, thus establishing the limiting distance between the two
      interfaces of the slab for multiple reflections between them to be considered
      important. A rigorous formulation for multiple-layered (M-layered) diffusive
      media is put forward, and a method for solving any M-layered medium is shown. The
      theory presented is used to characterize a two-layered medium from transmission
      measurements, showing that the coefficients of scattering, mu'(s) , and
      absorption, mu(a) , are retrieved with great accuracy. Finally, we demonstrate
      the simultaneous retrieval of both mu;(s) and mu(a).

PMID- 11318334
TI  - Optical trapping of dielectric particles in arbitrary fields.
AB  - We present a new method to calculate trapping forces of dielectric particles with
      diameters D < or = lambda in arbitrary electromagnetic, time-invariant fields.
      The two components of the optical force, the gradient force and the scattering
      force, are determined separately. Both the arbitrary incident field and the
      scatterer are represented by plane-wave spectra. The scattering force is
      determined by means of the momentum transfer in either single- or double
      scattering processes. Therefore the second-order Born series is evaluated and
      solved in the frequency domain by Ewald constructions. Numerical results of our
      two-force-component approach and an established calculation method are compared
      and show satisfying agreement. Our procedure is applied to investigate axial
      trapping by focused waves experiencing effects of aperture illumination and
      refractive-index mismatch.

PMID- 11318344
TI  - Corrections for inhomogeneities in biological tissue caused by blood vessels.
AB  - In tissue optics, the assumption that blood is homogeneously distributed in
      tissue can give rise to miscalculations because blood is found only in blood
      vessels. In our paper randomly oriented blood vessels are treated as particles
      for which we obtained apparent absorption and scattering coefficients by means of
      the Monte Carlo method. Apart from this correction for the contribution of blood
      properties in tissue, a correction for the contribution of the surrounding tissue
      proved to be needed as well. The results found with our model were compared with
      available results from the literature.

PMID- 11318346
TI  - Depolarization and blurring of optical images by biological tissue.
AB  - We present a study of the image blurring and depolarization resulting from the
      transmission of a narrow beam of light through a continuous random medium. We
      investigate the dependence of image quality degradation and of depolarization on
      optical thickness, correlation length of the inhomogeneities, and incident
      polarization state. This is done numerically with a Monte Carlo method based on a
      transport equation that takes into account polarization of light. We compare our
      results with those for transport in media with discrete spherical scatterers. We
      show that depolarization effects are different in these two models of biological
      tissue.

PMID- 11318350
TI  - Adding up antimicrobial use.

PMID- 11318351
TI  - The future of animal health.

PMID- 11318352
TI  - Wild mustangs get special care from Special Forces.

PMID- 11318353
TI  - Encourages use of vaccination titers.

PMID- 11318354
TI  - More comments on ethics of alternative therapies.

PMID- 11318355
TI  - More coments on ethics of alternative therapies.

PMID- 11318356
TI  - What is your diagnosis? Minimal soft-tissue swelling of the tarsocrural and
      proximal intertarsal joints and a minimally displaced oblique slab fracture of
      the third tarsal bone.

PMID- 11318357
TI  - What is the standard of care for a veterinarian, and does departure from it
      always spell liability?

PMID- 11318358
TI  - Assessing the association between the geographic distribution of deer ticks and
      seropositivity rates to various tick-transmitted disease organisms in dogs.
AB  - OBJECTIVE: To determine whether the geographic distribution of deer ticks (Ixodes
      scapularis) was associated with the distribution of dogs seropositive for various
      tick-transmitted disease organisms (ie, Borrelia burgdorferi, Rickettsia
      rickettsii, the human granulocytic ehrlichiosis [HGE] agent, Ehrlichia canis, and
      Bartonella vinsonii subsp berkhoffii). DESIGN: Serologic survey. SAMPLE
      POPULATION: Serum samples from 277 dogs in animal shelters and veterinary
      hospitals in Rhode Island. RESULTS: Overall, 143 (52%) dogs were seropositive for
      B burgdorferi, 59 (21.3%) were seropositive for R rickettsii, 40 (14.4%) were
      seropositive for the HGE agent, 8 (2.9%) were seropositive for E canis, and 6
      (2.2%) were seropositive for B vinsonii. Regression analysis indicated that the
      natural logarithm of nymphal deer tick abundance was correlated with rate of
      seropositivity to the HGE agent and to B burgdorferi but not to rate of
      seropositivity to R rickettsii, E canis, or B vinsonii. Percentages of samples
      seropositive for B burgdorferi, R rickettsii, the HGE agent, and E canis were
      significantly higher for samples from the southwestern part of the state where
      ticks in general and deer ticks in particular are abundant than for samples from
      the northern and eastern portions of the state, where ticks are relatively rare.
      CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that all 5 disease agents
      are in Rhode Island and pose a risk to dogs and humans. Knowledge concerning tick
      distributions may be useful in predicting the pattern of disease associated with
      particular tick species and may aid diagnostic, prevention, and control efforts.

PMID- 11318359
TI  - Effects of hydromorphone or oxymorphone, with or without acepromazine, on
      preanesthetic sedation, physiologic values, and histamine release in dogs.
AB  - OBJECTIVE: To compare hydromorphone with oxymorphone, with or without
      acepromazine, for preanesthetic sedation in dogs and assess changes in plasma
      concentration of histamine after drug administration. DESIGN: Randomized clinical
      study. ANIMALS: 10 healthy mixed-breed dogs. PROCEDURE: Dogs were treated IM with
      hydromorphone (group H), oxymorphone (group O), hydromorphone with acepromazine
      (group H/A), or oxymorphone with acepromazine (group O/A). Sedation score, heart
      rate, respiratory rate, systolic blood pressure, and oxygen saturation were
      recorded at baseline immediately after drug administration (T0) and every 5
      minutes for 25 minutes (T25). Plasma histamine concentration was measured at
      baseline and T25. RESULTS: Sedation was similar between groups H and 0 at all
      times. Sedation was significantly greater for groups H/A and O/A from T10 to T25,
      compared with other groups. Systolic blood pressure was significantly reduced at
      T25 in group H/A, compared with group H, and in group O/A, compared with group O.
      Prevalence of panting at T25 was 50% for groups H and O, compared with 20% for
      group H/A and 30% for group O/A. By T25, heart rate was significantly lower in
      all groups. Oxygen saturation was unaffected by treatment. Mean +/- SD plasma
      histamine concentration was 1.72 +/- 2.69 ng/ml at baseline and 1.13 +/- 1.18
      ng/ml at T25. There was no significant change in plasma histamine concentration
      in any group. CONCLUSIONS AND CLINICAL RELEVANCE: Hydromorphone is comparable to
      oxymorphone for preanesthetic sedation in dogs. Sedation is enhanced by
      acepromazine. Neither hydromorphone nor oxymorphone caused an increase in plasma
      histamine concentration.

PMID- 11318360
TI  - Percutaneous ultrasonographically guided radiofrequency heat ablation for
      treatment of primary hyperparathyroidism in dogs.
AB  - OBJECTIVE: To evaluate the efficacy and safety of ultrasonographically guided
      radiofrequency heat ablation of parathyroid masses in dogs with primary
      hyperparathyroidism. DESIGN: Clinical trial. ANIMALS: 11 dogs. PROCEDURE: In all
      dogs, either 1 or 2 parathyroid masses were evident ultrasonographically. Dogs
      were anesthetized, and a 20-gauge over-the-needle catheter was directed into the
      parathyroid mass via ultrasonographic guidance. Radiofrequency heat was applied
      to the stylet of the catheter until there was sonographically apparent change to
      the entire parenchyma of the mass. Serum total and ionized calcium and
      parathyroid hormone concentrations were monitored daily for 5 days after the
      ablation procedure and again at 1, 2, and 3-month intervals, if possible. Dogs
      were monitored for adverse effects. RESULTS: One treatment was required in 6
      dogs, 2 treatments were required in 2 dogs, and treatment was unsuccessful in 3
      dogs. Serum total and ionized calcium concentrations were within reference ranges
      within 2 days of the last procedure in all 8 successfully treated dogs. Serum
      parathyroid hormone concentration was decreased 24 hours after treatment in all 8
      dogs. Hypocalcemia developed in 5 of the 8 successfully treated dogs, all of
      which required treatment. One dog had a transient voice change. Other adverse
      effects were not reported. CONCLUSIONS AND CLINICAL RELEVANCE:
      Ultrasonographically guided radiofrequency heat ablation of parathyroid masses is
      a safe and effective alternative to surgery in dogs with primary
      hyperparathyroidism.

PMID- 11318361
TI  - Epidemiology of feline infectious peritonitis among cats examined at veterinary
      medical teaching hospitals.
AB  - OBJECTIVE: To determine proportions of cats in which feline infectious
      peritonitis (FIP) was diagnosed on an annual, monthly, and regional basis and
      identify unique characteristics of cats with FIP. DESIGN: Case-control study.
      SAMPLE POPULATION: Records of all feline accessions to veterinary medical
      teaching hospitals (VMTH) recorded in the Veterinary Medical Data Base between
      January 1986 and December 1995 and of all feline accessions for necropsy or
      histologic examination at 4 veterinary diagnostic laboratories. PROCEDURE:
      Proportions of total and new feline accessions for which a diagnosis of FIP was
      recorded were calculated. To identify characteristics of cats with FIP, cats with
      FIP were compared with the next cat examined at the same institution (control
      cats). RESULTS: Approximately 1 of every 200 new feline and 1 of every 300 total
      feline accessions at VMTH in North America and approximately 1 of every 100
      accessions at the diagnostic laboratories represented cats with FIP. Cats with
      FIP were significantly more likely to be young, purebred, and sexually intact
      males and significantly less likely to be spayed females and discharged alive
      than were control cats. The proportion of new accessions for which a diagnosis of
      FIP was recorded did not vary significantly among years, months, or regions of
      the country. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that FIP
      continues to be a clinically important disease in North America and that sexually
      intact male cats may be at increased risk, and spayed females at reduced risk,
      for FIP. The high prevalence of FIP and lack of effective treatment emphasizes
      the importance of preventive programs, especially in catteries.

PMID- 11318363
TI  - Clinical outcome of dogs with grade-II mast cell tumors treated with surgery
      alone: 55 cases (1996-1999).
AB  - OBJECTIVE: To determine outcome for dogs with grade-II mast cell tumors treated
      with surgery alone. DESIGN: Retrospective study. ANIMALS: 55 dogs. PROCEDURES:
      Medical records were examined, and signalment; location and size of tumor;
      staging status; dates of local recurrence, metastasis, death, or last follow-up
      examination; status of surgical margins; previous surgery; postoperative
      complications; and cause of death were recorded. Follow-up information was
      obtained via reexamination or telephone conversations with owners or referring
      veterinarians. Univariate analysis was performed to identify prognostic factors.
      RESULTS: 60 tumors in 55 dogs were included. Median follow-up time was 540 days.
      Three (5%) mast cell tumors recurred locally; median time to local recurrence was
      62 days. Six (11%) dogs developed another mast cell tumor at a different
      cutaneous location; median time to a different location was 240 days. Three (5%)
      dogs developed metastases; median time to metastasis was 158 days. Fourteen dogs
      died; 3 deaths were related to mast cell tumor, and 7 were unrelated. The
      relationship with mast cell tumor was not known for 4. Median survival times were
      151, 841, and 827 days, respectively, for these 3 groups. Forty-six (84%) dogs
      were free of mast cell tumors during the study period. A reliable prognostic
      factor could not be identified. CONCLUSIONS AND CLINICAL RELEVANCE: Results
      suggest that additional local treatment may not be required after complete
      excision of grade-II mast cell tumors and that most dogs do not require systemic
      treatment.

PMID- 11318362
TI  - Evaluation of interoperator variance in shunt fraction calculation after
      transcolonic scintigraphy for diagnosis of portosystemic shunts in dogs and cats.
AB  - OBJECTIVE: To determine interoperator variance in shunt fraction calculation.
      DESIGN: Case series. SAMPLE POPULATION: 101 transrectal portoscintigraphic
      studies. PROCEDURE: Results of dynamic portoscintigraphic studies were reviewed
      by 4 radiologists without knowledge of signalment, history, or medical profile.
      Results were judged to be negative or positive on the basis of the dynamic scan.
      Composite images were formulated, and hand-drawn regions of interest were
      determined for the heart and liver. Time-activity curves were generated, time
      zero points were selected, curves were integrated during a 10-second interval,
      and shunt fractions were calculated. RESULTS: Radiologists were in agreement
      regarding positive versus negative results for 99 of 101 studies. Interoperator
      variance in shunt fraction calculation ranged from 0.4 to 59.6%. For 51 studies
      with positive results, variance ranged from 2.5 to 59.6% (mean +/- SD, 22.8 +/-
      14.5%); differences among reviewers were significant. For 48 studies with
      negative results, variance in shunt fraction ranged from 0.4 to 25.9% (mean, 5.3
      +/- 5.8%); significant differences among reviewers were not detected. Shunt
      fraction calculations were not exactly reproducible among radiologists in 94 and
      100% of studies with negative or positive results, respectively. CONCLUSIONS AND
      CLINICAL RELEVANCE: Results suggest that shunt fraction values are not
      reproducible among operators. Range in variability was greater in studies with
      positive results. This factor may be of particular clinical importance in
      reassessment of patients after incomplete shunt ligation.

PMID- 11318364
TI  - Hyperglycemia in dogs and cats with head trauma: 122 cases (1997-1999).
AB  - OBJECTIVE: To determine whether hyperglycemia is associated with head trauma in
      dogs and cats and whether the degree of hyperglycemia corresponds to severity of
      neurologic injury or outcome. DESIGN: Retrospective study. ANIMALS: 52 dogs and
      70 cats with head trauma and 122 age- and species-matched control dogs and cats.
      PROCEDURE: Severity of head trauma was classified as mild, moderate, or severe.
      Blood glucose concentrations recorded within 1 hour after admission were compared
      between case and control animals and among groups when case animals were grouped
      on the basis of severity of head trauma or outcome. RESULTS: Blood glucose
      concentration was significantly associated with severity of head trauma in dogs
      and cats and was significantly higher in dogs and cats with head trauma than in
      the control animals. However, blood glucose concentration was not associated with
      outcome. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that dogs and cats
      with head trauma may have hyperglycemia and that degree of hyperglycemia was
      associated with severity of head trauma. However, degree of hyperglycemia was not
      associated with outcome for dogs and cats with head trauma. Because hyperglycemia
      can potentiate neurologic injury, iatrogenic hyperglycemia should be avoided in
      patients with head trauma.

PMID- 11318365
TI  - Effect of hydroxyethyl starch infusion on colloid oncotic pressure in
      hypoproteinemic horses.
AB  - OBJECTIVE: To determine the effect of hydroxyethyl starch (HES) on colloid
      oncotic pressure (pi) during fluid resuscitation of hypoproteinemic horses and to
      evaluate the clinical usefulness of direct and indirect methods for determination
      of pi before and after infusion of a synthetic colloid. DESIGN: Prospective
      clinical study. ANIMALS: 11 hypoproteinemic horses. PROCEDURE: Horses received IV
      infusions of 8 to 10 ml of a 6% solution of HES/kg (3.6 to 4.5 ml/lb) of body
      weight during fluid resuscitation. Blood samples were obtained for determination
      of plasma measured colloid oncotic pressure (pi meas) and plasma total protein
      and albumin (A) concentrations. Plasma globulin concentration (G) was calculated
      as the difference between plasma total protein and albumin concentrations.
      Calculated values for colloid oncotic pressure (piA + G) were determined by use
      of a predictive nomogram previously developed for horses. RESULTS: There was no
      significant difference between the means of pi meas and piA + G at the beginning
      of HES infusion. After HES infusion, the mean of pi meas was increased
      significantly from baseline for 6 hours. Mean plasma total protein and albumin
      concentrations and piA + G were decreased significantly from baseline for 24
      hours. Differences between mean pi meas and piA + G after HES infusion were
      significant for 24 hours. CONCLUSIONS AND CLINICAL RELEVANCE: There was good
      agreement between plasma pi meas and piA + G in blood samples obtained from
      hypoproteinemic horses immediately before infusion of HES. Use of a predictive
      nomogram did not, however, account for the oncotic effect of HES. Results of
      comparison of pi meas to piA + G after HES infusion suggest that a significant
      oncotic effect was maintained for 24 hours in the study horses.

PMID- 11318366
TI  - Risk factors for and outcomes of noncatastrophic suspensory apparatus injury in
      Thoroughbred racehorses.
AB  - OBJECTIVE: To evaluate effects of toe grabs, exercise intensity, and distance
      traveled as risk factors for subclinical to mild suspensory apparatus injury
      (SMSAI) in Thoroughbred racehorses and to compare incidence of severe
      musculoskeletal injury (MSI) in horses with and without SMSAI. DESIGN: Nested
      case-control study. ANIMALS: 219 Thoroughbred racehorses racing or in race
      training. PROCEDURE: Racehorses were examined weekly for 90 days to determine
      incidence of suspensory ligament injury and monitor horseshoe characteristics.
      Every horse's exercise speeds and distances were recorded daily. Conditional
      logistic regression was used to compare exposure variables between incident case
      (n = 25) and selected control (125) horses. Survival analysis was used to compare
      time to MSI for horses with (n = 41) and without (76) SMSAI. RESULTS: The best
      fitting logistic model for the data included age (< 5 vs > or = 5 years old), toe
      grab height the week of injury (none vs very low, low, regular, or Quarter Horse
      height), and weekly distance the week preceding injury (miles). Although the 95%
      confidence intervals for all odds ratios included 1, the odds for SMSAI appeared
      to increase with the presence of a toe grab, higher weekly distance, and age > or
      = 5 years. Horses that had SMSAI were significantly more likely to have a severe
      MSI or severe suspensory apparatus injury than were horses that did not.
      CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that pre-existing SMSAI is
      associated with development of severe MSI and severe suspensory apparatus injury.
      Modifying training intensity and toe grab height for horses with SMSAI may
      decrease the incidence of severe MSI.

PMID- 11318367
TI  - Identification of sources of Salmonella organisms in a veterinary teaching
      hospital and evaluation of the effects of disinfectants on detection of
      Salmonella organisms on surface materials.
AB  - OBJECTIVE: To determine sources of Salmonella organisms in a veterinary teaching
      hospital, compare bacterial culture with polymerase chain reaction (PCR) testing
      for detection of Salmonella organisms in environmental samples, and evaluate the
      effects of various disinfectants on detection of Salmonella organisms on surface
      materials. DESIGN: Prospective study. SAMPLE POPULATION: Fecal samples from 638
      hospitalized horses and 783 environmental samples. PROCEDURE: Standard bacterial
      culture techniques were used; the PCR test amplified a segment of the Salmonella
      DNA. Five disinfectants were mixed with Salmonella suspensions, and bacterial
      culture was performed. Swab samples were collected from 7 surface materials after
      inoculation of the surfaces with Salmonella Typhimurium, with or without addition
      of a disinfectant, and submitted for bacterial culture and PCR testing. RESULTS:
      Salmonella organisms were detected in fecal samples from 35 (5.5%) horses. For
      environmental samples, the proportion of positive bacterial culture results
      (1/783) was significantly less than the proportion of positive PCR test results
      (110/783), probably because of detection of nonviable DNA by the PCR test.
      Detection of Salmonella organisms varied with the surface material tested, the
      method of detection (bacterial culture vs PCR testing), and the presence and type
      of disinfectant. CONCLUSIONS AND CLINICAL RELEVANCE: Results of the present study
      suggested that Salmonella organisms can be isolated from feces of hospitalized
      horses and a variety of environmental surfaces in a large animal hospital.
      Although recovery of Salmonella organisms was affected by surface material and
      disinfectant, bleach was the most effective disinfectant on the largest number of
      surfaces tested.

PMID- 11318368
TI  - An outbreak of salmonellosis among horses at a veterinary teaching hospital.
AB  - Between May 1996 and February 1997, 27 horses and a veterinary student at a
      veterinary teaching hospital developed apparent nosocomial Salmonella Typhimurium
      infection. The source of the multiple-drug resistant Salmonella Typhimurium was a
      neonatal foal admitted for treatment of septicemia. A high infection rate (approx
      13% of hospitalized horses) coupled with a high case fatality rate (44%) for the
      initial 18 horses affected led to a decision to close the hospital for extensive
      cleaning and disinfection. Despite this effort and modification of hospital
      policies for infection control, 9 additional horses developed nosocomial
      Salmonella Typhimurium infection during the 6 months after the hospital reopened.
      Polymerase chain reaction testing of environmental samples was useful in
      identifying a potential reservoir of the organism in drains in the isolation
      facility. Coupled with clinical data, comparison of antimicrobial resistance
      patterns of Salmonella Typhimurium isolates provided a rapid initial means to
      support or refute nosocomial infection. Although minor changes in the genome of
      these isolates developed over the course of the outbreak, pulsed-field gel
      electrophoresis testing further supported that salmonellosis was nosocomial in
      all 27 horses.

PMID- 11318369
TI  - Susceptibility of cattle to infection with Ehrlichia equi and the agent of human
      granulocytic ehrlichiosis.
AB  - OBJECTIVE: To determine susceptibility of cattle to infection with Ehrlichia equi
      and the agent of human granulocytic ehrlichiosis (HGE). DESIGN: Experimental
      disease and prevalence survey. ANIMALS: 6 cattle, 2 horses, and 2,725 serum
      samples from healthy cattle. PROCEDURE: 2 cattle and 1 horse were inoculated with
      E equi, 2 cattle and 1 horse were inoculated with the HGE agent, and 2 cattle
      served as sham-inoculated controls; inoculated animals were evaluated via
      clinical, hematologic, serologic, and real-time polymerase chain reaction tests.
      Prevalence of antibodies against E equi in 2,725 healthy cattle was determined by
      use of an indirect immunofluorescent technique. RESULTS: No abnormal clinical or
      hematologic findings or inclusion bodies within granulocytes were observed in the
      cattle after inoculation, and results of all polymerase chain reaction tests were
      negative. Seroconversion in inoculated cattle developed 10 to 12 days after
      inoculation (reciprocal titers, 160). Both horses developed clinical signs of
      ehrlichiosis. Five of 2,725 (0.18%) cattle were seropositive for E equi, with
      titers ranging from 20 to 80. All seropositive cattle originated from the same
      tick-rich region in the Sierra Nevada foothills. CONCLUSIONS AND CLINICAL
      RELEVANCE: Results suggest that cattle are not susceptible to infection with E
      equi or the agent of HGE and that prevalence of exposure to E equi in healthy
      cattle is low. Therefore, E equi and the agent of HGE are likely of negligible
      importance for cattle in North America.

PMID- 11318370
TI  - Evaluation of a commercial ELISA for diagnosis of paratuberculosis in cattle.
AB  - OBJECTIVE: To evaluate sensitivity and specificity of a new ELISA for antibodies
      against Mycobacterium avium subsp paratuberculosis. DESIGN: Cross-sectional
      observational survey. SAMPLE POPULATION: Serum samples from 590 cattle that were
      infected with M avium subsp paratuberculosis and 723 cattle that were not
      infected. PROCEDURE: Serum samples were tested by use of an ELISA for antibodies
      against M avium subsp paratuberculosis. RESULTS: Sensitivity of the test varied
      from 15.4 to 88.1%, depending on the clinical stage and bacterial shedding status
      of the cattle. CONCLUSIONS AND CLINICAL RELEVANCE: Results obtained with use of
      the new ELISA agreed favorably with those of a previous ELISA. Practitioners must
      be aware of variability in the sensitivity of the test, which depends on the
      clinical and shedding status of the cattle, because this may affect
      interpretation of test results.

PMID- 11318371
TI  - Thigh splints in a young female soccer player.

PMID- 11318372
TI  - Current readings in nuclear medicine.

PMID- 11318373
TI  - Sensory responses of descending brain neurons in the walking cricket, Gryllus
      bimaculatus.
AB  - Sensory responses of various descending brain neurons, their modulation during
      standing or walking, and the correlation of such modulations with stimulus
      category were investigated. Stimuli involving (1) static or moving grating,
      artificial calling songs with (2) the conspecific and (3) an ultrasound
      frequency, or (4) air puffs to the cerci were presented to crickets walking in an
      open loop paradigm. The morphology of different descending interneurons in the
      brain and thoracic ganglia is described, together with their respective response
      properties. Some cells were excited, others inhibited by, and only some were
      directionally sensitive to the optomotor stimulus. Responses to artificial
      calling songs with conspecific and ultrasound frequency differed in the way the
      syllables of the sounds were coded and in the representation of ipsi- and
      contralateral stimuli. The majority of cells tested responded to air puffs.
      Stimulus representation differed among individuals of morphological types, but
      was very similar among individual interneurons of the morphologically homogenous
      i5 group. Stimuli approximating predators (air puffs, ultrasound) were usually
      represented during walking and standing; however, most neurons only responded to
      the other stimuli only during walking. These results indicate that the same
      neurons show different responses, and may have different functions, under
      different behavioral conditions.

PMID- 11318374
TI  - Proportional inhibition in the cricket medial giant interneuron.
AB  - Inhibitory effects on the number of wind-evoked impulses were studied in the
      medial giant interneuron of the cricket, Gryllus bimaculatus. The interneuron
      receives an inhibitory input from wind receptors on cercus ipsilateral to its
      soma. Using a dual channel wind stimulator, the intensity of inhibitory input was
      changed over 1,000-fold and effects on the number of spikes were observed. The
      ipsilateral inhibition reduced the number of outgoing spikes from a level
      elicited by excitation alone and it did so in proportion to the level of wind
      responsiveness displayed by each cell. A proportional coefficient of inhibition
      was derived and its value depended on the level of total excitation of the medial
      giant interneuron. The medial giant interneurons with high excitation showed a
      smaller value of the coefficient than those with low excitation. The proportional
      inhibition of the medial giant interneuron by the ipsilateral cercus suppresses
      the number of its spikes to a reasonable level for a wide range of stimulus
      intensities under natural conditions.

PMID- 11318375
TI  - The units of perception in the antiphonal calling behavior of cotton-top tamarins
      (Saguinus oedipus): playback experiments with long calls.
AB  - We investigated how the acoustic structure of the cotton-top tamarin monkey's
      (Saguinus oedipus) combination long call relates to the antiphonal calling
      behavior of conspecifics. Combination long calls can function as contact calls
      and are produced by socially isolated individuals. Often conspecifics respond to
      these calls with their own long calls. Structurally, these calls are always
      composed of one or more 'chirps' followed by two or more 'whistles'. We compared
      the antiphonal calling responses to playbacks of complete, naturally produced
      long calls versus single whistles or single chirps. Subjects responded
      significantly more to whole calls than to either syllable-type alone. Thus, our
      data suggest that, in terms of the antiphonal calling behavior of socially
      isolated conspecifics, the whole long call is the unit of perception.

PMID- 11318376
TI  - Visual interneurons of the crab Chasmagnathus studied by intracellular recordings
      in vivo.
AB  - Comparative physiology of visual systems has become an important field of
      investigation. However, despite the fact that Crustacea represents a major
      phylogenetic group, research on the physiology of vision of these animals is
      scant and almost limited to the crayfish. We developed a preparation to study in
      vivo the visual nervous system of a semiterrestrial crab through intracellular
      recordings. The response to a pulse of light was investigated in 206 interneurons
      from 38 animals. Seventy-eight of these neurons could be classified by functional
      criteria as sustaining cells, dimming cells, nonspiking hyperpolarizing cells and
      nonspiking depolarizing cells. Quantitative description is provided for the first
      two groups and qualitative description is given for the last two. The remaining
      neurons presented a broad range of different types of phasic responses to light.
      Although semiterrestrial crabs are behaviorally more reactive to visual stimuli
      than the crayfish, the general physiological properties of identified lamina and
      medullary neurons of Chasmagnathus resemble those of the crayfish. The results
      described here represent the first attempt to study the visual system of crabs
      with intracellular recordings and constitute the beginning of a project aimed to
      investigate the neuronal functions underlying behavioral responses elicited by
      visual stimuli.

PMID- 11318377
TI  - Plasticity of the electric organ discharge waveform of male Brachyhypopomus
      pinnicaudatus. II. Social effects.
AB  - Many electric fish produce sexually dimorphic electric organ discharges. Although
      electric organ discharges are comprised of action potentials, those of the
      Gymnotiform family Hypopomidae show significant plasticity in response to stress
      and time of day. We show here that male Brachyhypopomus pinnicaudatus (Hopkins
      1991), adjusts the degree of sexual dimorphism in its electric organ discharge
      depending on immediate social conditions. Three to five days of isolation
      resulted in gradual decrease of two sexually dimorphic waveform characters:
      duration and amplitude. Introduction of a second fish to the experimental tank
      restored electric organ discharge duration and amplitude. Duration recovered
      quicker than amplitude, and both recovered faster in the presence of males than
      females. In studies of other electric fish species, treatment with steroid sex
      hormones have taken several days to increase sexual dimorphism in the electric
      organ discharge. The socially induced changes seen in this study are initiated
      too quickly to involve classic steroid action of genomic transcription and thus
      may depend on another mechanism. Socially induced regulation of the male's
      electric organ discharge waveform is consistent with the compromises in signaling
      strategy shown by other taxa with costly sexual advertisement signals.

PMID- 11318378
TI  - Octopamine influences division of labor in honey bee colonies.
AB  - Forager honey bees have higher brain levels of octopamine than do bees tending
      larvae in the hive. To test the hypothesis that octopamine influences honey bee
      division of labor we treated bees orally with octopamine or its immediate
      precursor tyramine and determined whether these treatments increased the
      probability of initiating foraging. Octopamine treatment significantly elevated
      levels of octopamine in the brain and caused a significant dose-dependent
      increase in the number of new foragers. This effect was seen for precocious
      foragers in single-cohort colonies and foragers in larger colonies with more
      typical age demographies. Tyramine treatment did not increase the number of new
      foragers, suggesting that octopamine was exerting a specific effect. Octopamine
      treatment was effective only when given to bees old enough to forage, i.e., older
      than 4 days of age. Treatment when bees were 1-3 days of age did not cause a
      significant increase in the number of new foragers when the bees reached the
      minimal foraging age. These results demonstrate that octopamine influences
      division of labor in honey bee colonies. We speculate that octopamine is acting
      in this context as a neuromodulator.

PMID- 11318379
TI  - The effect of sound intensity on duration-tuning characteristics of bat inferior
      collicular neurons.
AB  - Previous studies have shown that inferior collicular neurons of the big brown
      bat, Eptesicus fuscus, serve as short-, band-, long- and all-pass filters for
      sound durations. Neurons with band-, short- and long-pass filtering
      characteristics discharged maximally to a specific sound duration or a range of
      sound durations. In contrast, neurons with all-pass filtering characteristics do
      not have duration selectivity. To determine if duration-tuning characteristics of
      collicular neurons were tolerant to changes in sound intensity, we examined the
      duration-tuning characteristics of collicular neurons using a wide range of sound
      intensities. Duration-tuning characteristics examined included the type,
      bandwidth and slope of duration-tuning curves. Sound intensity delivered within
      20 dB of minimum threshold did not affect duration-tuning characteristics of all
      collicular neurons studied. Sound intensities at still higher levels did not
      affect the tuning characteristics of two-thirds of collicular neurons but
      decreased the duration selectivity and changed the duration-tuning curves of the
      remaining one-third of neurons from one type to another. However, these two
      groups of duration-tuning collicular neurons were not separately organized inside
      the inferior colliculus. The biological relevance of these findings to bat
      echolocation is discussed.

PMID- 11318380
TI  - Female sex pheromone of a wandering spider (Cupiennius salei): identification and
      sensory reception.
AB  - Females of the wandering spider Cupiennius salei attach a sex pheromone to their
      dragline. Males encountering the female dragline examine the silk thread with
      their pedipalps and then typically initiate reciprocal vibratory courtship with
      the sexual partner. The female pheromone was identified as (S)-1,1'-dimethyl
      citrate. The male pheromone receptive sensory cells are located in tip pore
      sensilla and respond to touching the sensillum tip with female silk or pieces of
      filter paper containing the synthetic pheromone.

PMID- 11318381
TI  - First identification and localization of a visual pigment in Hydra (Cnidaria,
      Hydrozoa).
AB  - The cnidarian Hydra does not possess identified photoreceptive structures or
      specialized cells for light detection; nevertheless, it shows a marked
      photosensitivity. So far no evidence has been previously reported about the
      localization of the proteins involved in the photoresponse. We used polyclonal
      antibodies and immunofluorescence microscopy on whole-mount Hydra to identify a
      putative rhodopsin-like protein. Our results show an immunoreactivity in the
      ectodermal layer of Hydra, which corresponds in position to the nervous epidermal
      sensory cells. These data provide the first identification of a rhodopsin-like
      protein in a phylogenetically old invertebrate and give a new insight into the
      Hydra photoreceptive response.

PMID- 11318382
TI  - Ergonomics evaluation of zinc pot skimming.

PMID- 11318383
TI  - Collecting industrial hygiene field data: practical experiences with a handheld
      computer.

PMID- 11318384
TI  - The year 2000 in ergonomics.

PMID- 11318385
TI  - Controlling formaldehyde exposures during embalming. National Institute for
      Occupational Safety and Health.

PMID- 11318386
TI  - Using water sprays to improve performance of a flooded bed dust scrubber.

PMID- 11318387
TI  - Validation for a recirculation model.
AB  - Recent Clean Air Act regulations designed to reduce volatile organic compound
      (VOC) emissions have placed new restrictions on painting operations. Treating
      large volumes of air which contain dilute quantities of VOCs can be expensive.
      Recirculating some fraction of the air allows an operator to comply with
      environmental regulations at reduced cost. However, there is a potential impact
      on employee safety because indoor pollutants will inevitably increase when air is
      recirculated. A computer model was developed, written in Microsoft Excel 97, to
      predict compliance costs and indoor air concentration changes with respect to
      changes in the level of recirculation for a given facility. The model predicts
      indoor air concentrations based on product usage and mass balance equations. This
      article validates the recirculation model using data collected from a C-130
      aircraft painting facility at Hill Air Force Base, Utah. Air sampling data and
      air control cost quotes from vendors were collected for the Hill AFB painting
      facility and compared to the model's predictions. The model's predictions for
      strontium chromate and isocyanate air concentrations were generally between the
      maximum and minimum air sampling points with a tendency to predict near the
      maximum sampling points. The model's capital cost predictions for a thermal VOC
      control device ranged from a 14 percent underestimate to a 50 percent
      overestimate of the average cost quotes. A sensitivity analysis of the variables
      is also included. The model is demonstrated to be a good evaluation tool in
      understanding the impact of recirculation.

PMID- 11318388
TI  - Cardiovascular disturbances in workers exposed to carbon disulfide.
AB  - According to literature data myocardial infarction was often the first noticeable
      effect of CS2 on the cardiovascular system. Therefore, a question arises whether
      earlier circulatory lesions are absent in CS2-exposed people, or they are present
      but are not detectable by the diagnostic methods used. The aim of our study has
      been to determine whether electrocardiological disturbances do occur in exposed
      people, and their association, if any, with the level of CS2 exposure. Modern
      diagnostic methods (resting and 24-h ECG, heart rate variability, late
      ventricular potential analysis, and long-term blood pressure monitoring) were
      used to answer this question. The examination comprised 177 male workers aged 24
      66 years (44+/-12), employed under conditions of the exposure for 5-38 years
      (14+/-9), and 93 male workers non-exposed to CS2 aged 23-65 years (41+/-12).
      Results of our studies show that abnormalities in resting and/or 24-h ECG
      recordings occur significantly more frequently in people exposed to CS2 than in
      the controls. ECG abnormalities were found primarily among the workers with a
      long, over 20-year, period of exposure. The considerable coincidence between the
      questionnaire and ECG results was found (87% reported complaints were confirmed
      by ECG data). Therefore it seems that all CS2-exposed people reporting heart
      symptoms should be subjected to a detailed examination. The frequency of late
      ventricular potentials in CS2-exposed people was not higher than in the controls.
      It may indicate that the ECG disturbances observed in those people were
      associated with functional rather than organic changes. Results of long-term ABP
      monitoring did not show increased incidence of elevated blood pressure in the
      exposed group. As the levels of the risk factors of ischemic heart disease in the
      exposed and control groups were similar, it seems that exposure to CS2 was
      responsible for the significant changes in the circulatory system.

PMID- 11318389
TI  - End-user exposures to synthetic vitreous fibers: II. Fabrication and installation
      fabrication of commercial products.
AB  - This article summarizes the results of exposure monitoring conducted during the
      installation and fabrication of commercial synthetic vitreous fiber (SVF)
      products. Included in this investigation were fiberglass duct insulation and
      construction applications (duct board, duct liner, and duct wrap), pipe and
      vessel insulation, batt insulation for prefabricated homes, and general
      fiberglass products. Commercial mineral wool products sampled as a part of this
      investigation included ceiling tiles, building safing, and loose insulation for
      prefabricated homes. A total of 520 valid air samples were collected as a part of
      this investigation and were analyzed using gravimetric, phase contrast microscopy
      (PCM), or scanning electron microscopy (SEM). Airborne fiber-size distributions
      were also determined for a subset of samples collected for SEM analysis. As a
      result of the task-based sampling strategy used in this study, sample times
      reflect exposures over the time the person was actually engaged in SVF-related
      work activities, and exposure results are therefore presented as task-length
      averages (TLAs). Thirty-five total dust samples were collected as a part of this
      investigation, resulting in 14 TLAs ranging from 0.3 to 7.6 mg/m3. A total of 125
      PCM-based TLAs were collected, with the mean TLA time for all product and
      occupation categories ranging from 277 to 443 minutes. The mean PCM-based TLAs
      for all product/occupations were below 1.0 f/cm3, ranging from 0.04 to 0.68
      f/cm3. A total of 116 SEM TLAs were determined. Average SEM-based TLA
      concentrations were slightly lower than the PCM-based estimates and ranged from
      <0.01 to 0.16 f/cm3. The geometric mean fiber diameters for commercial products
      and occupations sampled as a part of the investigation ranged from 0.8 microm to
      1.9 microm. Geometric mean fiber length varied by a factor of approximately
      three, ranging from 9.5 microm to 29.5 microm.

PMID- 11318390
TI  - Characterization of publication rotogravure press emission rates and
      compositions.
AB  - Emission compositions and rates were determined during production for a
      publication rotogravure press room at a large rotogravure printing company. The
      press room housed a single 4-color, 8-print-stand press, with an 84" paper web.
      Average press speed was 1800 feet per minute. Data were collected over a 2-day
      period and included measurements of ventilation, room area concentrations, duct
      exhaust compositions, amount and composition of inks used, and worker exposures.
      These data were used with mass balance models that were appropriate for the
      workspace. Toluene comprised more than 90 percent of the inks and solvents and
      accounted for more than 90 percent of the press emissions. Average toluene
      emissions during press operation and press off conditions were 222 kg/hr and 8-38
      kg/hr, respectively. The uncontrolled toluene emission on the basis of printed
      paper throughput was 3 g/m2. Of the total toluene released, 90 percent was
      captured by the local exhaust ventilation. The measured control efficiency was
      much lower than the average efficiency of 97 percent for the month of the test
      reported by the plant. A mass balance model evaluation demonstrated that only the
      lower efficiency was consistent with measured room concentrations. Using the
      measured emission rates and actual monthly press on and press off conditions, the
      difference in efficiency for the plant (10 rotogravure presses) extrapolates to
      the additional release to the workspace and ambient environment of over 700
      tons/yr of toluene.

PMID- 11318391
TI  - The effects of temperature and pressure on airborne exposure concentrations when
      performing compliance evaluations using ACGIH TLVs and OSHA PELs.
AB  - Occupational hygienists perform air sampling to characterize airborne contaminant
      emissions, assess occupational exposures, and establish allowable workplace
      airborne exposure concentrations. To perform these air sampling applications,
      occupational hygienists often compare an airborne exposure concentration to a
      corresponding American Conference of Governmental Industrial Hygienists (ACGIH)
      threshold limit value (TLV) or an Occupational Safety and Health Administration
      (OSHA) permissible exposure limit (PEL). To perform such comparisons, one must
      understand the physiological assumptions used to establish these occupational
      exposure limits, the relationship between a workplace airborne exposure
      concentration and its associated TLV or PEL, and the effect of temperature and
      pressure on the performance of an accurate compliance evaluation. This article
      illustrates the correct procedure for performing compliance evaluations using
      airborne exposure concentrations expressed in both parts per million and
      milligrams per cubic meter. In so doing, a brief discussion is given on the
      physiological assumptions used to establish TLVs and PELs. It is further shown
      how an accurate compliance evaluation is fundamentally based on comparison of a
      measured work site exposure dose (derived from the sampling site exposure
      concentration estimate) to an estimated acceptable exposure dose (derived from
      the occupational exposure limit concentration). In addition, this article
      correctly illustrates the effect that atmospheric temperature and pressure have
      on airborne exposure concentrations and the eventual performance of a compliance
      evaluation. This article also reveals that under fairly moderate conditions of
      temperature and pressure, 30 degrees C and 670 torr, a misunderstanding of how
      varying atmospheric conditions affect concentration values can lead to a 15
      percent error in assessing compliance.

PMID- 11318392
TI  - Toxicity of 2,6-Di-tert-butyl-4-Nitrophenol (DBNP).
AB  - U.S. Navy submarines reported a yellowing of metal surfaces on their internal
      surfaces. The yellowing was initially identified on the painted steel bulkheads
      but further examination indicated that it was not limited to steel surfaces and
      included bedding, thread tape, Formica, plastisol covered hand-wheels, and
      aluminum lockers. Crew members also reported to the medical department that their
      skin turned yellow when they came in contact with these contaminated surfaces and
      requested information on the effects of exposure. Studies conducted by General
      Dynamics' Electric Boat Division (EBD) determined that the agent was 2,6-Di
      tertbutyl-4-Nitrophenol (DBNP). 2,6-Di-butylphenol (DBP) is an antioxidant
      additive used in lubricating oils and hydraulic fluids. In the enclosed
      atmosphere of a submarine, the oil mist could be spread throughout the boat by
      venting the lube oil to the atmosphere. Submarines use electrostatic
      precipitators (ESP) to clean the air of particulate materials. During passage
      through the ESP, oil mist containing DBP is nitrated to DBNP, which is then moved
      throughout the boat in the ventilation system. Analysis of the EBD data indicated
      24-hour exposure concentrations to be in the range of <3.0 to 122 ppb in the
      laboratory and submarine settings. Submarine crews may be exposed to these
      concentrations for as many as 24 hours/ day for 90 days during underway periods.
      Toxicity studies regarding the oral and dermal uptake of DBNP were conducted.
      From the literature the lethal dose to 50 percent of the population (LD50) of
      DBNP (rat) was reported by Vesselinovitch et al. in 1961 to be 500 mg/kg. Our
      studies indicated that the LD50 is in the range of 80 mg/kg in the rat. Our work
      also includes dermal absorption studies, which indicated that DBNP is not well
      absorbed through intact skin. Within this study, no no-observable adverse effect
      level (NOAEL) or lowest observable adverse effect level (LOAEL) was identified.
      Calculation of a reference dose was completed using standard methods based on the
      LD50 as a numerator with several uncertainty and modifying factors. EBD's
      determination of airborne concentrations aboard submarines fall in the range of
      these anticipated allowable concentrations and could indicate significant chronic
      exposures. No adverse effects from DBNP exposures have been reported to date.

PMID- 11318393
TI  - Treatment of opioid addiction in physicians' offices: it's about time.

PMID- 11318394
TI  - Drinking behavior and motivation for treatment among alcohol-dependent liver
      transplant candidates.
AB  - Alcohol misuse is the second most common indication for liver transplantation in
      the United States. Our post-transplant alcoholism treatment trial suggested that
      current interventions might not be transferable to liver transplantees. We sought
      to identify differences between patients awaiting liver transplantation and
      alcoholics entering treatment without severe liver disease. Thirty transplant
      patients were compared to thirty naltrexone study patients on medical status,
      alcohol and drug use, alcohol craving, motivation for treatment, psychiatric
      symptoms, and psychosocial problems. Lifetime alcohol consumption was greater for
      transplant patients compared to naltrexone patients. In contrast to the
      naltrexone group, transplant patients denied craving for alcohol and showed
      little motivation for alcoholism treatment. Groups did not differ on other
      psychosocial measures. Liver transplant patients differ from patients in
      alcoholism treatment trials on measures of alcohol consumption, alcohol craving
      and motivation for treatment. Alcoholism interventions should accommodate their
      medical condition and boost motivation for continued abstinence.

PMID- 11318396
TI  - Relationships between patient characteristics and unsuccessful substance abuse
      detoxification.
AB  - OBJECTIVE: History and laboratory evaluations are common for patients entering
      substance abuse detoxification programs. We sought to identify if patient history
      and laboratory characteristics entering a detoxification program were associated
      with unsuccessful detoxification. DESIGN: Retrospective cohort study of 186
      patients of a residential-inpatient short-term medical detoxification facility.
      Unsuccessful detoxification was defined as leaving for urgent medical referral or
      against program advice. RESULTS: Patients were predominantly male, middle-aged,
      minority, unemployed, and poly-substance users. Twenty-four patients (13%) did
      not complete the detoxification program (4 left for urgent medical referral, 20
      left against program advice). Unsuccessful detoxification was associated with
      nausea and/or vomiting (p = 0.032), Caucasian race (p = 0.002), and opiates as a
      drug of choice (p = 0.018). Laboratory abnormalities were common but none were
      associated with unsuccessful detoxification. CONCLUSIONS: For patients admitted
      to a medically monitored detoxification facility, few patient characteristics
      were associated with detoxification outcome. Routine admission laboratories
      without clinical correlation may be unwarranted.

PMID- 11318395
TI  - Report of the Council on Scientific Affairs: methadone maintenance and needle
      exchange programs to reduce the medical and public health consequences of drug
      abuse.
AB  - Extensive evaluation studies show that methadone maintenance therapy (MMT)
      reduces heroin use and associated problems in a cost-effective manner, without
      negative public health impact. MMT is limited by inadequate funding and
      understanding of relevant research, extensive regulation, and limits on the
      freedom of physicians to provide methadone in a variety of medical settings.
      Broad-based medical, public health, and scientific support exists for expansion
      of MMT with greater emphasis on consistency and quality, and provision of
      ancillary services. Programs for the exchange, free distribution, and legal
      pharmacy sale of needles and syringes reduce injection drug use and prevent the
      spread of bloodborne pathogens; drug abuse treatment and other services are
      important components. Neither strategy increases existing drug use nor leads to
      drug use initiation. The scientific literature supports assertions that drug
      abuse issues should be treated primarily as medical and public health rather than
      criminal justice issues. The effectiveness of both strategies warrants increased
      support for services, easing of federal and state restrictions governing their
      availability, and advocacy in their support.

PMID- 11318397
TI  - Gender, weight concerns, and adolescent smoking.
AB  - This study examined the beliefs that adolescents' hold regarding smoking and
      weight. In particular, this study examined the relationship between smoking
      status and self-perceptions of body weight. In addition, it examined gender and
      age differences in adolescent male and female smokers' beliefs about smoking and
      weight control. Analyses were conducted on the telephone interview responses of
      1,200 adolescent smokers and nonsmokers between the ages of 12 and 17. Chi-square
      analyses were utilized for univariate comparisons, and logistic regression for
      multivariate comparisons. Results revealed gender and age differences in
      perceptions of body weight. In addition, female smokers were more likely than
      male smokers to adhere to the belief that smoking controlled weight. While no
      relationship was observed between males' perceived weight and their smoking
      status, females who perceived themselves to be either overweight or underweight
      were more likely to smoke. Findings suggest a gender bias in processing
      social/environmental cues linking smoking and weight control.

PMID- 11318398
TI  - Therapeutic drug monitoring in methadone maintenance: choosing a matrix.
AB  - Methadone maintenance is the premier pharmacological treatment for opioid
      addiction, but it is rarely informed by evidence-based practice guidelines for
      dosage monitoring and adjustment. Such guidelines are crucial because the
      pharmacokinetics of methadone vary greatly among patients, and this variation may
      account for differences in treatment outcome. We review the pharmacokinetics of
      methadone and factors that may alter it (including drug interactions, disease
      states, and idiosyncratic differences among patients). Also reviewed are
      prospects for therapeutic drug monitoring (TDM) of methadone in plasma, urine,
      sweat, and saliva. Due to its ease of collection and its presumed representation
      of the bioavailable free-fraction of methadone, saliva may be a promising matrix.
      However, saliva methadone concentrations are influenced by salivary pH, and
      future studies are needed to determine how to control for that. Administrative,
      medical, and social implications of methadone TDM are briefly discussed.

PMID- 11318399
TI  - Buprenorphine treatment of heroin dependence (detoxification and maintenance) in
      a private practice setting.
AB  - At the conclusion of a 3-year demonstration project in a medical setting in which
      refusal to accept methadone was an inclusion criterion, 12 subjects were unable
      to detoxify from buprenorphine and remained adamant in their refusal to enroll in
      a MMTP. In order to study the feasibility of expanding opportunities for
      treatment previously unavailable to this under-served population of heroin
      addicts, these 12 subjects plus an additional 11 subjects (N = 23) were recruited
      for a 12 months trial of buprenorphine treatment conducted in an office-based
      setting on a fee-for-service basis. An additional cohort of 40 heroin dependent
      subjects were entered in a protocol for detoxification only. The findings
      demonstrate both feasibility and patient acceptance of office based fee-for
      service buprenorphine treatment, supporting the need for (1) additional studies
      of this population and (2) changes in government regulations to reintroduce
      addiction treatment under physician auspices in private practice settings.

PMID- 11318400
TI  - Somatic comorbidity of addicts: does hospitalization yield relevant findings?
AB  - The aim of this prospective study was to examine the severity and character of
      somatic comorbidity when addicted patients were admitted to hospital for
      detoxification. The study was conducted at a university-based psychiatric clinic.
      Somatic comorbidity was registered by laboratory, radiological and
      electrocardiographic parameters and by the amount of non-psychiatric
      consultations. Besides the number of patients with dual diagnosis interpreted as
      combination of addictive and psychiatric diseases was registered. A total of 111
      consecutive patients (32 women) was divided into patients with alcohol dependence
      and patients with other addictive diseases including polydrug abuse and opiate
      dependence. Patients with alcohol dependence were characterized by an elevated
      heart rate and higher values for gamma-glutamyltransferase. No significant
      differences between groups could be found for the rate corrected QT interval and
      cardiothoracic ratio. Although viral liver disease was diagnosed in both groups
      patients with a history of injecting drug use were at greatest risk for hepatitis
      C. About one-third of all patients required consultant non-psychiatric treatment.
      Concomitant heart and pulmonary diseases were more pronounced in the alcohol
      dependence group. The findings emphasize that hospitalization of addicted
      patients yields relevant somatic morbidity which has an impact on cost and
      requires medically supervised detoxification programs.

PMID- 11318401
TI  - Changes in alcohol-related inpatient care--an international trend comparison.
AB  - This paper studies two utilization measures of alcoholism treatment, discharge
      rate and average length of stay, in the United States, Australia, Sweden and
      Canada. The results suggest that the decline in length of stay and discharges in
      the past 15 years was an international phenomenon and not unique to the U.S.
      However, data for length of stay also suggests that the biggest decline in the
      United States coincided with the fastest growth of managed behavioral health
      care.

PMID- 11318402
TI  - Determination of fluoroquinolones in serum using an on-line clean-up column
      coupled to high-performance immunoaffinity-reversed-phase liquid chromatography.
AB  - A simple, rapid and reliable method for the simultaneous analysis of the
      fluoroquinolones ciprofloxacin, enrofloxacin, sarafloxacin, and difloxacin in
      bovine serum has been developed. Upon injection of serum samples, an on-line
      protein G-linked column was employed to automatically remove serum components
      that otherwise would interfere with analyses. A high-performance immunoaffinity
      chromatography (HPIAC) column containing covalently bound anti-sarafloxacin
      antibodies was then used to capture the fluoroquinolones while allowing the
      remainder of the serum components to elute to waste. After binding to the HPIAC
      column, the fluoroquinolones were eluted directly onto a reversed-phase (RP)
      column for final separation of the compounds prior to fluorescence detection at
      excitation and emission wavelengths of 280 and 444 nm, respectively. Due to use
      of a clean-up column in tandem with a highly selective HPIAC column, the only off
      line sample preparation required was dilution (10-fold) in phosphate buffered
      saline (PBS) and passage of the samples through a 0.2-microm filter to remove
      particulate matter prior to injection. No significant interferences from the
      sample matrix were observed, indicating good selectivity with the HPIAC column.
      The method yielded high recoveries from fortified bovine serum that were >95% for
      all four fluoroquinolones with good reproducibility (C.V. values <7.0%). The on
      line, automated method described here provides a simple, sensitive and specific
      assay for multiresidue detection of fluoroquinolones in serum.

PMID- 11318403
TI  - Determination of moxifloxacin in growth media by high-performance liquid
      chromatography.
AB  - A direct injection high-performance liquid chromatographic method with column
      switching has been developed to determine moxifloxacin in Mueller-Hinton broth. A
      LiChrocart 4-4 pre-column filled with a LiChrospher 100 RP 18, 5 microm and a 150
      x 4.6 mm I.D. column packed with a Supelcozil ABZ+ Plus were used and led to a
      retention time of 5.70 min. Fluorescence detection allowed one to reach a
      quantification limit of 0.05 microg/ml with a 100-microl sample size. The
      standard curves were linear from 0.05 to 3.2 microg/ml. Intra- and inter-day
      imprecisions within the linearity range were < or =4.76 and < or =5.75%,
      respectively. The mean relative errors for the same day and the day-to-day
      inaccuracies ranged from -2.93 to +4.50% and from -1.10 to +6.00%, respectively.
      The method was demonstrated to be useful for pharmacokinetic-pharmacodynamic
      studies of moxifloxacin in an in vitro model.

PMID- 11318404
TI  - Experimental design methodology applied to the study of channel dimensions on the
      elution of red blood cells in gravitational field flow fractionation.
AB  - Field flow fractionation (FFF) separation techniques have gained considerable
      success with micron-sized species. Living red blood cells (RBCs) of any origin
      have emerged as ideal models for cell separation development. Their elution mode
      is now described as "Lift-Hyperlayer". Certain separator dimension parameters are
      known to play a key role in the separation and band spreading process. Systematic
      studies of channel dimensions effects on RBC retention, band spreading, peak
      capacity and on a novel parameter described as "Particle Selectivity" were set up
      by means of a two-level factorial experimental design. From experimental results
      and statistical calculations it is confirmed that channel thickness plays a major
      role in retention ratio, peak variance, peak capacity and particle selectivity.
      Channel breadth strongly influences plate height, with lower impact on peak
      capacity and particle selectivity. Retention ratio, peak variance and peak
      capacity observed results are modulated by second-order interactions between
      channel dimensions. Preliminary rules for channel configurations are therefore
      set up and depend on separation goals. It is shown that a very polydisperse
      population is best disentangled in a thin and narrow channel whatever its length.
      If a mixture of many different micron-sized species is considered (each of
      limited polydispersities); a thick and broad channel should be preferred, with
      length modulating peak capacity to disentangle this polymodal mixture.

PMID- 11318405
TI  - Improvement in precision of the liquid chromatographic-electrospray ionization
      tandem mass spectrometric analysis of 3'-C-ethynylcytidine in rat plasma.
AB  - During the development of the liquid chromatography with electrospray ionization
      tandem mass spectrometry for the quantitative determination of 3'-C
      ethynylcytidine (I) in rat plasma, ion suppression caused by the matrix
      components was observed for I and its structural analogue, 3'-C-ethylcytidine
      (II) as the internal standard. In the method initially designed, I/II peak area
      ratios varied according to the degree of matrix effect, which led to the poor
      precision of the assay. From the examination of the ion suppression behavior for
      I and II, it was assumed that this phenomenon is attributed to the difference in
      the retention time between I and II. Based on this assumption, therefore, the
      methanol content in the mobile phase was changed from 5 to 25% so as to make I
      and II the same retention time. As a result of this modification of the initial
      method, the precision expressed as relative standard deviation was improved from
      5.2-16.2 to 2.7-4.2% in intra-assay and from 6.8-14.9 to 3.5-7.2% in inter-assay
      validations.

PMID- 11318406
TI  - Determination of aloesin in rat plasma using a column-switching high-performance
      liquid chromatographic assay.
AB  - A column-switching high-performance liquid chromatography (HPLC) method for the
      determination of aloesin in rat plasma using column-switching and ultraviolet
      (UV) absorbance detection is described. Plasma was directly injected onto the
      HPLC system consisting of a clean-up column, a concentrating column, and an
      analytical column, which were connected with a six-port switching valve. The
      determination of aloesin was accurate and repeatable, with a limit of
      quantitation of 10 ng/ml in plasma. The standard calibration curve for aloesin
      was linear (r=0.998) over the concentration range of 10-1000 ng/ml in rat plasma.
      The intra- and inter-day assay variabilities of aloesin ranged from 1.0 to 4.7%
      and 1.1 to 8.8%, respectively. This highly sensitive and simple method has been
      successfully applied to a pharmacokinetic study after oral administration of
      aloesin to rats.

PMID- 11318407
TI  - Simultaneous quantification of components of neoglycolipid-coated liposomes using
      high-performance liquid chromatography with evaporative light scattering
      detection.
AB  - Liposomes composed of dipalmitoylphosphatidylcholine (DPPC), cholesterol and a
      neoglycolipid, mannopentaose-conjugated dipalmitoylphosphatidylethanolamine (Man5
      DPPE), have been shown to have a strong adjuvant effect in inducing the antigen
      specific cellular immunity. In this study, a rapid and simple analytical method
      using a HPLC system with an evaporative light scattering detector was developed
      for simultaneous quantification of the liposome components Man5-DPPE, cholesterol
      and DPPC. The chromatographic separation of these components was performed using
      a trimethylsilane column with an isocratic mobile phase of chloroform-methanol
      water (1:33:6, v/v) after disrupting the liposomes with chloroform-methanol-water
      (10:10:3, v/v). This HPLC method provided sufficient reproducibility and
      linearity of calibration curves for the quantification of the liposome
      constituents. In addition, this method can be used for the quantification of
      various neoglycolipids with different carbohydrate structures.

PMID- 11318408
TI  - Evaluation of immobilized metal affinity chromatography for purification of
      penicillin acylase.
AB  - The aim of this work was to test immobilized metal affinity chromatography (IMAC)
      for the purification of penicillin acylase. After evaluation of different metals,
      Cu2+ was selected. Different samples were tested: pure penicillin acylase,
      industrial clarified feedstock and crude extract. After comparing two eluents,
      NH4Cl and imidazole, it appeared that although both gave good results for
      recovery and activity, NH4Cl was a more selective eluent with a higher fold
      purification than imidazole (4.64 versus 2.04). Moreover, we shown that a
      multistep gradient of NH4Cl, greatly increased the degree of purification (12.36)
      compared with the one-step process as control (4.64). In addition, good recovery
      was obtained (97-100%).

PMID- 11318409
TI  - Determination of albumin and myoglobin in dialysate and ultrafiltrate samples by
      high-performance size-exclusion chromatography.
AB  - A high-performance size-exclusion chromatographic method was developed, validated
      and implemented for simultaneous and quantitative determination of albumin and
      myoglobin along with inulin, vancomycin and creatinine in dialysate and
      ultrafiltrate samples from in vitro hemodialysis experiments. The experimental
      parameters including mobile phase pH, ionic strength, detection wavelength, flow
      rate, injection volume were first optimized for the determination of albumin,
      myoglobin, inulin, vancomycin and creatinine. The peak height ratio and detection
      limits of the proteins were then comparatively studied at 210, 254 and 280 nm by
      UV and diode array detection. The method was further validated by evaluating the
      linearity, precision and accuracy of the proteins. The assay was finally
      implemented to the simultaneous and quantitative determination of the proteins in
      dialysate and ultrafiltrate samples.

PMID- 11318410
TI  - Analytical method of heparan sulfates using high-performance liquid
      chromatography turbo-ionspray ionization tandem mass spectrometry.
AB  - We established a highly sensitive quantitative analytical method of heparan
      sulfates (HS) by LC-MS-MS. It became possible to determine the unsaturated
      disaccharides produced by the enzyme digestion of HS, and to perform the whole
      analyses on one sample within 3 min by use of a short column of CAPCELL PAK NH2
      UG80 (35 mm x 2 mm I.D.). The assay method was validated and showed the
      satisfactory sensitivity, precision and accuracy, which enabled the quantitation
      up to picomol level. By employing this method, we performed the analyses of HS in
      mouse brain and liver, and tumor tissues of tumor-bearing mouse transplanted
      subcutaneously with Meth A fibrosarcoma cells. The compositions of the
      unsaturated disaccharide units derived from HS were found to be somewhat
      different among those tissues. It is assumed that the site of sulfation in HS may
      be controlled by certain regulatory mechanisms. The quantitative method developed
      in this study is believed to be a very useful method for the determination of
      compositional profiles of constitutive disaccharide units of tissue HS.

PMID- 11318411
TI  - Degradation kinetics of aplidine, a new marine antitumoural cyclic peptide, in
      aqueous solution.
AB  - The degradation kinetics of aplidine were investigated using reversed-phase high
      performance liquid chromatography combined with UV detection. Aplidine consists
      of at least two isomers that undergo interconversion at a low rate. Influences of
      pH, temperature, buffer ions and ionic strength on the degradation kinetics were
      studied. The log kobs) -pH profile can be divided into three parts, a proton, a
      solvent and a hydroxyl-catalysed section. The stability-indicating properties of
      the used analysis technique as well as the identities of the main degradation
      products were checked using gradient liquid chromatography and mass spectrometric
      detection. The overall degradation rate constant as a function of the temperature
      under acidic and alkaline conditions obeys the Arrhenius equation. No catalytic
      influences were observed with phosphate and carbonate buffers and, in addition,
      the ionic strength showed no substantial effect on the stability, as expected.
      Results from gradient LC-MS indicated that hydrolysis of the ester groups present
      in the ring structure was the main degradation route. There is no difference in
      degradation rate constants for the individual isomers.

PMID- 11318412
TI  - Stereoselective determination of ofloxacin and its metabolites in human urine by
      capillary electrophoresis using laser-induced fluorescence detection.
AB  - A capillary electrophoresis method for the simultaneous separation and
      enantioseparation of the antibacterial drug ofloxacin and its metabolites
      desmethyl ofloxacin and ofloxacin N-oxide in human urine has been developed and
      validated. Enantioseparation was achieved by adding sulfobutyl beta-cyclodextrin
      to the running buffer. The detection of the analytes was performed by laser
      induced fluorescence (LIF) detection using a HeCd-laser with an excitation
      wavelength of 325 nm. In comparison with conventional UV detection, LIF detection
      provides higher sensitivity and selectivity. The separation can be performed
      after direct injection of urine into the capillary without any sample
      preparation, because no matrix compounds interfere with the assay. Additionally,
      the high sensitivity of this method allows the quantification of the very low
      concentrations of enantiomers of both metabolites. The limit of quantification
      was 250 ng/ml for ofloxacin enantiomers and 100 ng/ml for each metabolites'
      enantiomers. This method was applied to the analysis of human urine samples
      collected from a volunteer after oral administration of 200 mg of (+/-)-ofloxacin
      to elucidate stereoselective differences in the formation and excretion of the
      metabolites. It could be demonstrated that the renal excretion of the S
      configured metabolites, especially S-desmethyl ofloxacin, within the first 20 h
      after dosage, is significantly lower than that of the R-enantiomers.

PMID- 11318413
TI  - Rapid process for purification of an extracellular beta-xylosidase by aqueous two
      phase extraction.
AB  - A rapid process for purification of an extracellular beta-xylosidase with high
      purity was developed. The manipulation involved the precipitation of protein from
      culture medium and the extraction of enzyme from the resuspended crude protein
      solution by an aqueous-two phase separation. A linear random copolymer, PE62,
      with 20% ethylene oxide and 80% propylene oxide was employed in both stages of
      the purification. The enzyme was precipitated effectively by using 10% (w/v) PE62
      and 5% (w/v) Na2HPO4. The aqueous two-phase extraction was performed with PE62
      (10%)-NaH2PO4 (15%) as phase-forming reagent. SDS-PAGE analysis revealed that the
      purified enzyme is near homogeneity. The yield is about 100% with a purification
      factor of 8.8-fold. The whole process can be completed within an hour without any
      column chromatography.

PMID- 11318414
TI  - Micellar electrokinetic capillary chromatography quantification of cytosine
      arabinoside and its metabolite, uracil arabinoside, in human serum.
AB  - Cytosine arabinoside (Ara-C) is widely used to induce remission in adult
      granulocytic leukemia. High doses can be infused in refractory leukemia or in
      relapse. After injection, Ara-C is quickly metabolized to uracil arabinoside (Ara
      U), the main inactive metabolite. We here described a micellar electrokinetic
      capillary chromatography (MECC) method to simultaneously determine Ara-C/Ara-U in
      human serum using 6-O-methylguanine as an internal standard. The assay was linear
      from 6.25 to 200 microg/ml with a quantification limit between 3 and 6 microg/ml.
      The analytical precision was satisfactory between 2 and 4.3% (within-run) and 3.7
      and 7.3% (between-runs). This assay was applied to the analysis of serum from
      acute granulocytic leukemia patient treated by high doses cytarabine (3 g/m2 body
      surface).

PMID- 11318415
TI  - High-performance liquid chromatographic analysis of the tyrphostin AG1478, a
      specific inhibitor of the epidermal growth factor receptor tyrosine kinase, in
      mouse plasma.
AB  - The tyrphostin 4-(3-chloroanilino)-6,7-dimethoxyquinazoline (AG1478) is
      undergoing evaluation as a potential new anticancer agent. We have developed a
      specific and sensitive reversed-phase HPLC assay for AG1478 in mouse plasma. The
      method involves a rapid and simple extraction process followed by separation on a
      Symmetry C8 stationary phase with a gradient of acetonitrile in ammonium acetate
      buffer. A linear response was achieved over the concentration range of 0.2-100
      microM using multilevel calibration with internal standard method of calculation.
      Inter- and intra-assay accuracy and precision were better than +/-10%. The limit
      of quantitation was 0.2 microM. We have used this method to study the preclinical
      pharmacokinetics of this new agent in mice.

PMID- 11318416
TI  - Optimized analytical method for cyclosporin A by high-performance liquid
      chromatography-electrospray ionization mass spectrometry.
AB  - The Micromass Platform LCZ mass detector parameters were optimized for
      simultaneous recording of the protonated (CsA-H+), sodium adduct (CsA-Na+) and
      potassium adduct (CsA-K+) of cyclosporin A eluted from a Symmetry Shield RP8
      column. The optimized procedure allows a precise analysis of CsA in whole blood
      or serum without removal of salts prior to analysis. The ratio of the three forms
      of CsA varied depending on the assay condition and the types of specimens being
      analyzed. The summation of three ionic forms of CsA detected by LC-ESI-MS is a
      reliable and simple method to assess CsA concentration in the blood.

PMID- 11318417
TI  - High-performance liquid chromatography assay for simultaneous determination of
      dextromethorphan and its main metabolites in urine and in microsomal
      preparations.
AB  - An HPLC method has been developed and validated for the determination of
      dextromethorphan, dextrorphan, 3-methoxymorphinan and 3-hydroxymorphinan in urine
      samples. Deconjugated compounds were extracted on silica cartridges using
      dichloromethane/hexane (95:05, v/v) as an eluent. Chromatographic separation was
      accomplished on a Phenyl analytical column serially connected with a Nitrile
      analytical column. The mobile phase consisted of a mixture of an aqueous
      solution, containing 1.5% acetic acid and 0.1% triethylamine, and acetonitrile
      (75:25, v/v). Compounds were monitored using a fluorescence detector. Calibration
      curves were linear over the range investigated (0.2-8.0 microM) with correlation
      coefficients >0.999. The method was reproducible and precise. Coefficients of
      variation and deviations from nominal values were both below 10%. For all the
      analytes, recoveries exceeded 77% and the limits of detection were 0.01 microM.
      The validated assay proved to be suitable for the determination of DEM metabolic
      indexes reported to reflect the enzymatic activity of the cytochrome P450s,
      CYP2D6 and CYP3A, both in vivo, when applied to urine samples from patients, and
      in vitro, when applied to samples from the incubation of liver microsomes with
      dextromethorphan.

PMID- 11318418
TI  - Separation of free amino acids in human plasma by capillary electrophoresis with
      laser induced fluorescence: potential for emergency diagnosis of inborn errors of
      metabolism.
AB  - Free amino acids (AAs) in human plasma are derivatized with 3-(4
      carboxybenzoyl)quinoline-2-carboxaldehyde (CBQCA) and analyzed by capillary
      electrophoresis (CE) with laser induced fluorescence (LIF) detection. The
      labeling procedure is significantly improved over results reported previously.
      Derivatization can be completed in 40 min, with concentrations as low as 4 x 10(
      8) M successfully labeled in favourable cases. Twenty-nine AAs (including 2
      internal standards) are identified and can be reproducibly separated in 70 min.
      Migration time RSD values for 23 of these AAs were calculated and found in the
      range from 0.5 to 4%. The rapid derivatization procedure and the resolution
      obtained in the separation are sufficient for a semi-quantitative, emergency
      diagnosis of several inborn errors of metabolism (IEM). Amino acid profiles for
      both normal donor plasma samples and plasma samples of patients suffering from
      phenylketonuria, tyrosinemia, maple syrup urinary disease, hyperornithinemia, and
      citrullinemia are studied.

PMID- 11318419
TI  - Analysis of corticosteroids in equine urine by liquid chromatography-mass
      spectrometry.
AB  - A liquid chromatography-mass spectrometry (LC-MS) method for the analysis of
      corticosteroids in equine urine was developed. Corticosteroid conjugates were
      hydrolysed with beta-glucuronidase; free and enzyme-released corticosteroids were
      then extracted from the samples with ethyl acetate followed by a base wash. The
      isolated corticosteroids were detected by LC-MS and confirmed by LC-MS-MS in the
      positive atmospheric pressure chemical ionisation mode. Twenty-three
      corticosteroids (comprising hydrocortisone, deoxycorticosterone and 21 synthetic
      corticosteroids), each at 5 ng/ml in urine, could easily be analysed in 10 min.

PMID- 11318420
TI  - Determination of the antihypertensive drug cilazapril and its active metabolite
      cilazaprilat in pharmaceuticals and urine by solid-phase extraction and high
      performance liquid chromatography with photometric detection.
AB  - A liquid chromatographic method with photometric detection for the determination
      of cilazapril and its active metabolite and degradation product cilazaprilat in
      urine and pharmaceuticals has been developed. The chromatographic method
      consisted of a microBondapak C18 column maintained at 30+/-0.2 degrees C, using a
      mixture of methanol-10 mM phosphoric acid (50:50 v/v) as mobile phase at a flow
      rate of 1.0 ml/min. Enalapril maleate was used as internal standard. The
      detection was performed at a wavelength of 206 nm. A study of the retention of
      cilazapril and cilazaprilat using solid-liquid extraction has been carried out in
      order to optimise the clean-up procedure for urine samples, which consisted of a
      solid-liquid extraction using C(R) cartridges. Recoveries greater than 85% are
      obtained for both compounds. The method was sensitive, precise and accurate
      enough to be applied to the determination of urine samples obtained from three
      hypertensive patients up to 24 h after intake of a therapeutic dose (detection
      limit of 70 ng/ml for cilazapril and cilazaprilat in urine). A comparison of the
      method developed using photometric and amperometric detection has been carried
      out.

PMID- 11318421
TI  - Reduction of animal usage by serial bleeding of mice for pharmacokinetic studies:
      application of robotic sample preparation and fast liquid chromatography-mass
      spectrometry.
AB  - Typically, pharmacokinetic studies in mice require one animal per time point,
      thus resulting in differences due to dosing error, animal to animal variation and
      more importantly the euthanasia of a large number of animals. A method for the
      determination of pharmacokinetic data from serially bled mice to support early
      drug discovery is described. Sample analysis relies on liquid chromatography
      coupled with tandem mass spectrometry permitting robust and reproducible analysis
      requiring approximately 3 min per sample. Several parameters are discussed
      including the method of sample collection, preparation and analysis. The use of
      serially bled mice has lead to a remarkable reduction in animal usage and a
      corresponding reduction in compound required for such experiments. Using
      conventional methodology, a nine-point pharmacokinetic curve with four animals
      per time point would require 36 mice. With the method described below, only four
      mice in total are used and euthanasia is not required, permitting reuse after
      several weeks recovery and washout. Also, pharmacodynamic-pharmacokinetic
      correlation is possible and is demonstrated using a mouse model of diabetes.

PMID- 11318422
TI  - Measurement of fecal sulfide using gas chromatography and a sulfur
      chemiluminescence detector.
AB  - We describe a simple technique to measure sulfide in fecal homogenates (or any
      other liquid milieu), which involves acidification followed by the G.C.
      measurement of H2S in a gas space equilibrated with a small quantity of
      homogenate. An internal standard of Zn35S added to the homogenate permits
      correction for incomplete recovery of H2S in the gas space. The use of a sulfur
      chemiluminescence detector, which specifically and sensitively responds to sulfur
      containing compounds, greatly facilitates this measurement.

PMID- 11318423
TI  - Identification of the modifying sites of mono-PEGylated salmon calcitonins by
      capillary electrophoresis and MALDI-TOF mass spectrometry.
AB  - A capillary electrophoretic method (CE) was developed for the determination of
      the PEG-modification sites of three positional isomers of mono-PEG modified
      salmon calcitonins (mono-PEG-sCTs). Resistance to proteolytic degradation on the
      PEG modification sites resulted in different patterns of CE electropherograms for
      the tryptic digested mono-PEG-sCTs isomers, and the PEG modification sites were
      assigned accordingly. The PEG-modification sites were also confirmed directly by
      determining the molecular masses of the tryptic digested PEG-modified fragments
      of respective mono-PEG-sCT by the matrix-assisted laser desorption ionization
      time-of-flight (MALDI-TOF) mass spectrometry.

PMID- 11318424
TI  - High-performance liquid chromatography multiplex detection of two single
      nucleotide mutations associated with hereditary hemochromatosis.
AB  - High-performance liquid chromatography (HPLC) has been applied to the multiplex
      detection of the two single nucleotide mutations commonly found in hereditary
      hemochromatosis (HH). HH is associated with a major G to A transition at position
      845 (mutation Cys282Tyr) and a minor C to G transition at position 187 (mutation
      His63Asp) in the cDNA of the HFE gene. Two detection assays were developed based
      on HPLC analysis of restriction fragment length polymorphism (RFLP) or single
      nucleotide extension (SNE) products following multiplex PCR amplification. RFLP
      genotypes the two sites as dsDNA fragments of different lengths generated by
      restriction enzymes Rsa I/Bcl I. SNE extends primers 5'-adjacent to the sites of
      interest with a dideoxynucleotide triphosphate (ddNTP) to generate extended
      ssDNA. The identity of the added ddNTP reveals the identity of the original
      possible mutation site(s). Application of these methods with HPLC analysis
      provides simple and reliable genotyping for HH and can be applied to other single
      nucleotide polymorphism studies.

PMID- 11318425
TI  - Assessment of [18F]fluoroethylflumazenil metabolites using high-performance
      liquid chromatography and tandem mass spectrometry.
AB  - A simple procedure using HPLC and tandem mass spectrometry has been developed for
      the determination of fluoroethylflumazenil metabolites. Samples were precipitated
      with acetonitrile, evaporated to dryness followed by reconstitution with
      methanol. As mobile phase, 50 mM ammonium formate-methanol (58:42, v/v) was used.
      The method is valid both for cold and radiolabelled metabolites. Various cold
      metabolites (hydroxylated and/or dealkylated) were identified in rat and human
      microsome preparations. Radiolabelled metabolites arise from two or more
      transformations including hydroxylation. The methodology developed can be applied
      for further characterisation of metabolites, and for the determination of non
      metabolised [18F]fluoroethylflumazenil in routine clinical analysis.

PMID- 11318426
TI  - Practice of solid-phase extraction and protein precipitation in the 96-well
      format combined with high-performance liquid chromatography-ultraviolet detection
      for the analysis of drugs in plasma and brain.
AB  - C18 Empore 96-well extraction disc plates have been employed for the analysis of
      three drugs with different polarities in plasma in conjunction with HPLC-UV,
      rufinamide, ICL670 and an anticonvulsant agent (AA1) in an early stage of
      development. With the most polar compound (AA1), ion-pair extraction at pH 12 was
      applied. The method developed for the assay of AA1 in plasma was applied to its
      determination in brain using an Oasis HLB plate following homogenisation in a pH
      7.4 buffer and protein precipitation with NaOH-ZnSO4, thereby saving time for
      method development. Protein precipitation in the 96-well format with filtration
      of the precipitate was applied to the determination of ICL670, a highly protein
      bound compound (>99.5%), with a good recovery (78%). Reversed-phase
      chromatography was applied using a short 5 cm column packed with 3 microm
      particles for the determination of ICL670 and AA1 and two parallel columns (15 cm
      long) for the determination of rufinamide. The methods were used routinely, one
      plate per analysis day being processed, resulting in increase in sample
      throughput and saving in solvents.

PMID- 11318427
TI  - Simultaneous determination of quinine and four metabolites in plasma and urine by
      high-performance liquid chromatography.
AB  - The determination of quinine, (3S)-3-hydroxyquinine, 2'-quininone and (10R)- and
      (10S)-10,11-dihydroxydihydroquinine in plasma and urine samples is described.
      This is the first time the R and S configurations have been correctly assigned to
      the two metabolites of 10,11-dihydroxyquinine. One hundred microliter-plasma
      samples were protein precipitated with 200 microl cold methanol. Urine samples
      were 10-100 x diluted and then directly injected into the HPLC. A reversed-phase
      liquid chromatography system with fluorescence detection and a Zorbax Eclipse XDB
      phenyl column and gradient elution was used. The within and between assay
      coefficients of variation of the method for quinine and its metabolites in plasma
      and urine was less than 13%. The lower limit of quantitation was in the range of
      0.024-0.081 microM.

PMID- 11318428
TI  - Protein determination by high-performance gel-permeation chromatography:
      applications to human pancreatic juice, human bile and tissue homogenate.
AB  - A high-performance gel-permeation chromatography (HPGPC) method to determine the
      proteins of human pancreatic juice, bile, and tissue homogenate has been
      developed. A diol-type silica gel column (35 x 8 mm I.D., 5 nm average pore
      diameter) was used under a column temperature of 8 degrees C. The eluent was
      acidic phosphate buffer with a high concentration of sodium chloride, nonionic
      detergent of polyoxyethylene (20) cetyl ether (Brij 58), glycerol and 2-propanol.
      The UV wavelength used for the protein detection was 210 nm. Analytical time was
      within 3.5 min. Good correlation coefficients were obtained with this HPLC method
      at a column temperature of 8 degrees C and a spectrophotometric bicinchoninic
      acid (BCA) method. A photometric pyrogallol-red molybdate complex method was
      found to correlate well with this HPLC method and with the BCA method only for
      tissue homogenate. Since this HPGPC protein assay method is simple, convenient,
      rapid, reproducible, and reliable, it is expected to be generally applicable to
      clinical and also to biochemical research.

PMID- 11318429
TI  - Stirrer tank: an appropriate technology to immobilize the CB.Hep-1 monoclonal
      antibody for immunoaffinity purification.
AB  - The CB.Hep-1 monoclonal antibody was coupled to CNBr-activated Sepharose CL 4B at
      three different immobilization scales for purification of recombinant hepatitis B
      surface antigen. Standard laboratory apparatus to obtain immunosorbents of 1 l
      (scale I) and 3 l (scale II) as well as a stirrer tank to prepare 6 l
      immunosorbents (scale III) were used. The binding capacity at scale III was 2-
      and 1.5-fold higher with respect to the scales II and I, while a reduction in the
      ligand leakage of 5- and 2-folds was observed. Immunosorbents from scale II
      showed a significantly reduced adsorption, and an increased ligand leakage.
      Differences in the coupling efficiency were not observed. Antigen purity eluted
      from the immunosorbents was always above 85%.

PMID- 11318430
TI  - Pharmacokinetic analysis by high-performance liquid chromatography of intravenous
      nordihydroguaiaretic acid in the mouse.
AB  - Nordihydroguaiaretic acid (NDGA) has been shown to inhibit both 5-lipoxygenase
      and ornithine decarboxylase and is active against several cancer cell lines and
      at least one mouse tumor model. Despite these findings, there have been no
      reports on the pharmacokinetics of NDGA. A reverse-phase high-performance liquid
      chromatography (HPLC) method was developed to detect NDGA in mouse plasma. The
      limit of detection of this method was 0.5 microg/ml. Administration of NDGA (50
      mg/kg, i.v.) to mice resulted in a peak plasma concentration of 14.7 microg/ml.
      The terminal half-life of NDGA was 135.0 min with a clearance of 201.9 ml/min x
      kg.

PMID- 11318431
TI  - Validated high-performance liquid chromatographic assay for simultaneous
      determination of dacarbazine and the plasma metabolites 5-(3-hydroxymethyl-3
      methyl-1-triazeno)imidazole-4-carboxamide and 5-(3-methyl-1-triazeno)imidazole-4
      carboxamide.
AB  - Dacarbazine (DTIC) is a prodrug that is clinically effective in the treatment of
      Hodgkin's disease, melanoma and soft tissue sarcoma. To better characterize the
      clinical pharmacology of parent drug and reactive metabolites, a reversed-phase
      HPLC method with UV detection was developed for simultaneous determination of
      dacarbazine and the metabolites 5-(3-hydroxymethyl-3-methyl-1-triazeno)imidazole
      4-carboxamide (HMMTIC) and 5-(3-methyl-1-triazeno)imidazole-4-carboxamide (MTIC).
      Chromatographic separation was achieved with a Zorbax SB-CN column and with a
      mobile phase of 80% 50 mM ammonium phosphate, pH 6.5, 20% methanol and 0.1%
      triethylamine. HMMTIC, MTIC and DTIC were extracted from plasma with methanol
      precipitation of the proteins. Recovery of DTIC and the metabolites from whole
      blood was greater than 92%. Rapid processing of whole blood, methanol extraction
      and storage at -70 degrees C substantially increased the stability of HMMTIC and
      MTIC from less than 15 min to 3 days. Precision for HMMTIC, MTIC and DTIC ranged
      from 3.7 to 16.3% relative standard deviation. The accuracy ranged from 101 to
      114% for all three analytes. The validated assay was used to determine the
      pharmacokinetic data for dacarbazine and its active metabolites for human
      patients with recurrent glioma receiving DTIC intravenously.

PMID- 11318432
TI  - Capillary electrophoretic profiling and pattern recognition analysis of urinary
      nucleosides from uterine myoma and cervical cancer patients.
AB  - Capillary electrophoretic (CE) profiling analysis combined with pattern
      recognition methods is described for the correlation between urinary nucleoside
      profiles and uterine cervical cancer. Nucleosides were extracted from urine
      specimens by solid-phase extraction in affinity mode using phenylboronic acid
      gel. CE separation was carried out with an uncoated fused-silica capillary (570
      mm x 50 microm I.D.) maintained at 20 degrees C, using 25 mM borate-42.5 mM
      phosphate buffer (pH 6.7) containing 200 mM sodium dodecyl sulfate as the run
      buffer under the applied voltage of 20 kV. A total of 15 nucleosides were
      positively identified in urine samples (2 ml) from eight uterine myoma (benign
      tumor group), 10 uterine cervical cancer (malignant tumor group) patients and 10
      healthy females (normal group) studied. The star symbol plots drawn based on each
      mean concentration of nucleosides normalized to that in normal group enabled one
      to discriminate malignant and benign groups from normal group. In addition,
      canonical discriminant analysis performed on the nucleoside data of 28 individual
      urine specimens correctly classified into three separate clusters according to
      groups in the canonical plot.

PMID- 11318433
TI  - State of the art neonatal hearing screening with auditory brainstem response.
AB  - The purpose of this paper is to briefly review some of the aspects of the
      auditory brainstem response (ABR) that are important in its use as a method of
      screening and assessing hearing in the neonate. The paper starts by considering
      the technical limitations of click ABR and explores the alternative
      electrophysiological methods. It then considers where ABR is required in the
      screening of neonates. The role of bone conduction ABR in estimating the
      conductive component of any hearing loss is discussed. Finally, the ability of
      the neonatal ABR to predict the long-term audiometric outcome of permanently
      hearing-impaired children is considered.

PMID- 11318434
TI  - A novel machine learning program applied to discover otological diagnoses.
AB  - A novel machine learning system, Galactica, has been developed for knowledge
      discovery from databases. This system was applied to discover diagnostic rules
      from a patient database containing 564 cases with vestibular schwannoma, bening
      paroxysmal positional vertigo, Meniere's disease, sudden deafness, traumatic
      vertigo and vestibular neuritis diagnoses. The rules were evaluated using an
      independent testing set. The accuracy of rules for these diagnoses were 91%, 96%,
      81%, 95%, 92% and 98%, respectively. Besides being accurate, the rules contained
      the five most important diagnostic questions identified in the earlier research.
      The knowledge presented with rules can be easily comprehended and verified.

PMID- 11318435
TI  - Using decision tree induction to model oculomotor data.
AB  - Decision tree induction is a machine learning method used to generate
      classification models from data sets. Numerous decision trees were constructed to
      examine relationships between oculomotor test parameters and lesion sites in a
      data set containing cases with operated cerebello-pontine angle tumour, operated
      hemangioblastoma, infarction of cerebello-brainstem and Meniere's disease, and
      control subjects. The aim was to find useful parameter combinations with
      discriminatory power. Decision trees constructed using both pursuit eye movements
      and saccadic eye movements yielded the best classification results. This is
      reasonable: oculomotor test results vary according to the site of the lesion and
      so the performance ability of subjects has to be taken into account in the
      classification. The decision tree program was able to generate classification
      models from the oculomotor data set. Generated decision trees were intelligible
      and can be utilized in physicians' research work.

PMID- 11318436
TI  - Long-term outcome of early childhood hearing impairments in northern Finland.
AB  - Early childhood hearing impairment (HI) may have a marked negative effect on
      educational outcome and employment status in adulthood. The late outcome of 51
      Finnish mildly to profoundly HId children born in the period 1965-1979 was
      studied using a questionnaire posted to the subjects. Subjects included in the
      study had an early childhood sensorineural, non-syndromal hearing impairment with
      no known associated handicaps. The response rate to the inquiry was as high as
      88% (45/51). The subjects had qualified educationally at a somewhat lower level
      than their age peers according to nationwide statistics; 48% of the respondents
      belonging to the labour force were currently unemployed (versus 15% of all the 25
      to 29-year-olds in Finland in 1997), but their employment status was not
      associated with the HI grade. In particular, the severely and profoundly HId
      often had needed special support from the employment authorities to find work.

PMID- 11318437
TI  - Neonatal hearing screening with transient evoked otoacoustic emissions-
      retrospective analysis on performance parameters.
AB  - The present paper reports on the implementation of a maternity based neonatal
      hearing-screening program in a private hospital. A retrospective analysis is
      performed on the test pass rate, the coverage and the number of children that
      become lost to follow-up. The data show a steady learning curve with a time
      course of several years. In the current screening practice, the test pass rate is
      at 99.0%, the coverage is at 96% (birth rate of 2000 per annum) and almost no
      babies get lost to follow-up.

PMID- 11318438
TI  - Assessment of the medial olivocochlear efferent system in children. pure tone 1.0
      kHz and 2.0 kHz suppressive effects on transient evoked otoacoustic emission.
AB  - The role of medial efferent system in regulating outer hair cell function has
      been studied by many investigators. Usually narrow band noise or white noise as
      contralateral stimulation (CS) suppressors have been used and changes in OAE
      amplitudes estimated. Thirty children aged 6-15 years (mean 12.5 +/- 4.7),
      without any changes in tonal and impedance audiometry and with negative history
      regarding otiatric diseases were examined. Transient evoked otoacoustic emissions
      (TEOAE) were recorded using ILO 92 Otodynamics Analyser. CS was performed using
      1.0 kHz and 2.0 kHz continuous pure tones of 30 dB SL or 50 dB SL. Effects of CS
      on TEOAE evoked by click of 80, 70 and 60 dB SPL were investigated. TEOAE
      analysis included assessment of TEOAE amplitude of half octave frequency
      bandwidth (HOFBW-1.0; HOFBW-1.5; HOFBW-2.0; HOFBW-3.0 and HOFBW-4.0 kHz) and 0.8
      kHz frequency bandwidth (0.8-FBW) amplitudes centred at 1.0; 2.0; 3.0; 4.0 and
      5.0 kHz. TEOAE amplitude recorded for stimuli 80, 70 and 60 dB SPL without CS
      decreased: mean values respectively 6.1 +/- 4.2; 5.4 +/- 4.5 and 3.3 dB SPL +/-
      4.3. CS effect on TEOAE was observed for all CS options, however, larger
      suppressive effect was recorded on TEOAE elicited by 70 dB SPL stimulus using 1
      kHz/50 dB SL tone as a suppressor and on TEOAE elicited by 60 dB SPL stimulus
      using 2 kHz/50 dB SL tone as a suppressor. HOFBW and 0.8-FBW analyses showed the
      association between the frequency/intensity of the suppressors and decreasing of
      amplitudes of adequate frequency bands. It is concluded that the described method
      of investigating of the medial olivocochlear efferent system seems to be
      sensitive and confirms frequency-dependent suppressive effect on OAE.

PMID- 11318439
TI  - Linear versus non-linear recordings of transiently-evoked otoacoustic emissions-
      methodological considerations.
AB  - A non-linear technique is predominantly used for the recording of transiently
      evoked otoacoustic emissions (TEOAEs). The aim of this study was to compare
      linear and non-linear TEOAE recordings. TEOAEs were recorded in 22 normal hearing
      subjects to clicks from 90 to 30 dB SPL in 10 dB steps with the ILO88 system
      using both linear and non-linear recording techniques. The non-linear recording
      technique reduces stimulus artifacts for early latencies, but total elimination
      could not be proved. Both artifact reduction and significant differences between
      the two kinds of TEOAE recordings were reduced for longer latencies and lower
      stimulus intensities. For longer latencies (>10 ms) there was no significant
      difference between "linear" and "non-linear" TEOAEs. A higher signal-to-noise
      ratio was found for "linear" TEOAEs, resulting in better identification and a
      higher test-retest correlation. The linear recording technique, which includes
      new methods of artifact cancellation in comparison to the mainly utilized non
      linear recording technique, should be used especially in hearing screening.

PMID- 11318440
TI  - DPOAE-patterns in different types of autosomal-dominant nonsyndromal hearing
      impairment.
AB  - Twelve families with autosomal-dominant nonsyndromal hearing impairment (ADNSHI)
      were examined. The mode of inheritance was determined by pedigree and at least
      three generations with affected persons had to be found. Pure tone audiogram
      (PTA), DP-gram and caloric vestibular test (CVT) were performed on 30 affected
      persons. By PTA we could find eight families with mild to moderate mid-frequency
      U-shaped ADNSHI, three families with moderate to severe gently sloping high tone
      ADNSHI and one family with variable ADNSHI. The corresponding DP-grams showed a
      family-specific DP-gram in 20 (66%) of the examined persons. Seven (23%) showed
      no distortion-product otoacoustic emissions (DPOAE). In three (10%) persons the
      DP-grams varied but were also abnormal. The CVT was normal in all cases.
      Obviously it is possible to find out typical DP-grams in families with ADNSHI.
      This could be used for early diagnosis of hearing disorders in newborns of such
      families. Problems could only occur in progredient cases.

PMID- 11318441
TI  - Latencies of the 2f1-f2 distortion product otoacoustic emissions measured using a
      phase-gradient method in young people, in the elderly and in people exposed to
      noise.
AB  - Distortion product otoacoustic emissions (DPOAE) are generally accepted as a good
      tool for investigating the micromechanics of the cochlea. The 2f1-f2 DPOAE
      latencies provide significant data regarding travelling waves. In this study the
      2f1-f2 DPOAE latencies were measured using a phase-gradient method, with a swept
      f2 procedure, for three groups: Group I comprised 60 healthy young people, aged
      17-32 years; Group II comprised elderly patients, aged 56-72 years, with
      presbyacusis; and Group III consisted of 74 miners, aged 19-35 years, who had
      been exposed to noise for 2-15 years. Measurements were performed for frequencies
      between 1.0 and 6.0 kHz. In all groups the latencies were fitted using a non
      linear regression model. The aim of the study was to compare the latency and
      amplitude of 2f1-f2 DPOAE in different inner ear pathologies. The highest DPOAE
      amplitudes were recorded in Group I and in miners with 2-4 years noise exposure
      (Group IIIa), and the latencies showed a similar pattern. The lowest DPOAE
      amplitudes were recorded in the elderly and in miners with 8-15 years noise
      exposure (Group IIIc), but in contrast the longest latencies were measured in
      miners and the shortest in the elderly. The latency analysis significantly
      reinforces opinions on the micromechanics of the cochlea, mostly in terms of the
      cochlear functioning as a filter and amplifier and with regard to the elasticity
      of the basilar membrane.

PMID- 11318442
TI  - Contralateral suppression of TEOAE in diabetic children. Effects of 1.0 kHz and
      2.0 kHz pure tone stimulation--preliminary study.
AB  - The medial efferent system and its regulating outer hair cell function have not
      been previously studied in diabetic children. In this study, the group comprised
      32 diabetic children, aged 6.0-16.0 years, with diabetes lasting 2.0-9.0 years,
      with normal tonal and impedance audiometry. A control group consisted of 30
      healthy children with similar age and sex distribution. Contralateral stimulation
      (CS) was performed using 1.0 and 2.0 kHz pure tones on the level of 30 and 50 dB
      SL. Effects of CS on transient evoked otoacoustic emissions (TEOAE) elicited by
      click of a level equal to 70 and 60 dB SPL were investigated. Analysis included
      assessment of TEOAE amplitude and 0.8 kHz frequency bandwidth (0.8-FBW)
      amplitudes (signal/noise) centred at 1.0; 2.0; 3.0; 4.0; 5.0 kHz. TEOAE-RA
      recorded for stimulus 80, 70 and 60 dB SPL without CS were decreasing: average
      values respectively 7.3, 4.7 and 3.9 dB SPL. In the group of diabetic children
      TEOAE amplitudes, recorded for different click levels without CS, were similar to
      these recorded in healthy children. It suggested that normal function of the
      cochlea was preserved, mostly outer hair cells. However, the obtained effects of
      CS, in comparison with healthy children, were weaker and not so regular.
      Statistical analysis revealed that the reduction of TEOAE amplitudes for adequate
      0.8-FBW in the control group was significantly higher, for both 1.0 kHz and 2.0
      kHz CPTs of 30 dB SL and 50dB SL, in comparison with diabetic children. It is
      concluded that the suppressive effect on OAE in diabetic children is rather weak
      and seems to be associated with pathological changes in medial olivo-cochlear
      myelinated fibres.

PMID- 11318443
TI  - Hand-held device for OAE-based screening.
AB  - In this paper, the main concepts realized in a handheld OAE device are described.
      These concepts are: weighted averaging, non-linear MLS technique, acoustic probe
      with flat response, electronic passport of the probe, communication with clinical
      databases, special language for device control.

PMID- 11318444
TI  - Applying signal statistical analysis to TEOAE measurements.
AB  - Automated detection of TEOAE gains increasing importance in screening
      applications. Conventional signal statistical analysis methods (buffer
      correlation and +/- difference) of TEOAE waveforms are compared with one another
      and with a method based on binomial statistics. It turns out that binomial
      statistics are more reliable and valid than conventional methods with common
      criteria. In particular, under narrowband noise conditions they are also faster.
      A frequency specific evaluation is hardly possible by means of conventional
      methods because of the high random correlation of narrow band signals.

PMID- 11318445
TI  - Analysis of spontaneous and click-evoked otoacoustic emissions in newborns.
AB  - This paper addresses the quantitative investigation of the contribution of
      spontaneous (SOAE) to click-evoked (TEOAE) otoacoustic emissions in newborns. The
      hypothesis was that a weighted linear combination of the spontaneous peaks is
      strongly similar to the corresponding click-evoked emissions. After
      identification of the main spontaneous peaks for each subject, a best fit
      procedure was applied to find the amplitude and phase of each spontaneous tone in
      the weighted summation. The comparison of the weighted signal (SpTEOAE) with the
      actual click-evoked response (TEOAE) from the same subject was performed,
      obtaining correlation coefficient higher than 50% in more than 100 ears over 132.

PMID- 11318446
TI  - Time-frequency analysis of neonatal click-evoked otoacoustic emissions.
AB  - Click-evoked otoacoustic emissions (CEOAEs) of full-term babies were considered.
      By means of the wavelet transform, each CEOAE was decomposed into frequency
      bands. The rms amplitude and test-retest correlation were computed from these
      bands. The results indicated that both the amplitude and correlation were not
      invariant with time but reached a maximum in specific time windows, depending on
      the frequency of the component. For all components, the correlation was greatly
      decreased for latencies > 12.5 ms. As a result, comparison between the
      performance of the default ILO 88 window (2.5-20 ms) and the 2.5-12.5 ms window
      showed that for all frequencies in the 1.5-6 kHz range there was a statistically
      significant improvement in the correlation.

PMID- 11318447
TI  - Distortion-product otoacoustic emission (DPOAE) following pure tone and wide-band
      noise exposures.
AB  - The aim of our investigations was to determine how the intensity of distortion
      product otoacoustic emission (DPOAE) changes following different sound and noise
      exposures. We performed examinations on 20 healthy people with normal hearing.
      DPOAEs were recorded scanning the 0.5-6 kHz frequency interval before and after
      the exposures. We exposed the subjects to 0.5, 1, 2, 4 and 6 kHz pure tones and
      wide-band noise (intensity: 80 dB HL, duration: 3 minutes). We conclude that the
      amplitudes of DPOAEs changed immediately after exposures at most frequencies.
      DPOAE intensities decreased at some frequencies in the middle frequency range (1
      2 kHz), and increased at low and particularly at high frequencies.

PMID- 11318448
TI  - Transiently evoked otoacoustic emissions as a prognostic indicator in idiopathic
      sudden hearing loss.
AB  - Idiopathic sudden sensorineural hearing loss (ISHL) remains a controversial
      topic. So far, there are no proven objective auditory factors to establish
      prognosis. Otoacoustic emissions reflect the functional integrity of the outer
      hair cells. The aim of this study was to assess the presence of transiently
      evoked otoacoustic emissions (TEOAEs) in the early stages of ISHL cases as a
      prognostic indicator. Thirty patients hospitalized for ISHL were included in the
      study. All patients underwent pure-tone audiometry (PTA) and TEOAE recordings on
      the admission day and at least three measures on the subsequent eight days. The
      audiometric threshold improvement at each frequency was correlated with the TEOAE
      parameters on each measure. Finally, the presence of TEOAEs on early examination
      was correlated with PTA threshold improvement. Twenty-three out of 30 patients
      experienced hearing recovery. Fourteen of the recovered patients had recordable
      TEOAEs or acceptable TEOAE peak amplitudes in some frequency bands on the first
      two measures, despite having audiometric thresholds greater than 40 dB HL. It
      thus seems that TEOAEs might serve as a clinical tool for prediction of recovery
      in ISHL cases.

PMID- 11318449
TI  - Medico-legal use of otoacoustic emissions in the audiological selection process
      for employment.
AB  - A 6-year experience of the Italian Air Force Medical Selection Centre in the
      audiological evaluation of candidates for employment is summarized. Otoacoustic
      emissions (OAEs) were introduced progressively from 1993 to analyse more
      effectively subjects affected with sensorineural hearing loss and reduce possible
      bias connected to standard audiometric tests. OAEs provided a useful tool to
      support pure-tone audiometry, providing more accurate audiological data. Finally,
      a reduction of medico-legal claims was observed in candidates undergoing OAE
      testing.

PMID- 11318450
TI  - Distortion product otoacoustic emissions in diabetics with normal hearing.
AB  - In 18 diabetic patients with normal hearing, distortion product otoacoustic
      emissions (DPOAEs) were measured. DPOAEs' amplitude and latency were analysed and
      compared with the data obtained from non-diabetic controls. The mean amplitude
      and latency were lower in diabetics than in controls. These results suggested
      that diabetes mellitus may induce the functional alteration of outer hair cells
      even in the normal hearing group. Further studies should be performed to evaluate
      the predictability of DPOAEs in hearing loss of the diabetic patient.

PMID- 11318451
TI  - Correlations between risk factors for hearing impairment and TEOAE screening test
      outcome in neonates at risk for hearing loss.
AB  - The aim of the study was to find the correlation between specific risk factors
      for hearing impairment as well as between risk factors and TEOAE screening
      results in neonates at risk for hearing impairment. Seventy-one newborns at risk
      for hearing impairment have been included in the study. Strong correlations
      between specific risk factors were found. Investigation of the relationship
      between specific risk factors and TEOAE signal-to-noise ratio (SNR) showed that
      in children with genetic risk factors, TORCH (toxoplasmosis, rubella, CMV, herpes
      virus, others) infections and in those treated with ototoxic drugs, the values of
      SNRs were significantly lower than in children at risk who did not present those
      factors. In case of hyperbilirubinaemic children the values of SNR were
      significantly higher than in the controls. In our opinion these relationships may
      be partially explained by the positive predictive values of these risk factors,
      but other intrinsic factors may also be involved.

PMID- 11318452
TI  - Amplitude modulation following responses in awake and sleeping humans--a
      comparison for 40 Hz and 80 Hz modulation frequency.
AB  - There have been several studies, which suggest that the amplitude of amplitude
      modulation following responses (AMFR) is correlated to the state of vigilance,
      similar to the 40 Hz event-related potentials. The aim of the present study was
      to compare the dependency of the AMFR-amplitude from the state of sleep for 40 Hz
      and 80 Hz modulation frequency. Eight normal hearing adults were investigated
      during natural and drug-induced sleep. The stimuli used were sinusoidally
      amplitude-modulated tones of 1 kHz carried frequency and 40 or 80 Hz modulation
      frequency at 60 dB nH stimulation level. For 40 Hz modulation frequency an
      increase of EEG-activity in the Delta-and Theta-band during periods of sleep
      correlates significantly with a decreased AMFR-amplitude whereas for 80 Hz no
      significant relation between stage of sleep and AMFR-amplitude could be found.
      The results suggest that in audiological use of 40 Hz-AMFR the state of vigilance
      should be monitored and stabilized at a high level.

PMID- 11318453
TI  - Brainstem auditory-evoked potential examinations in diabetic patients.
AB  - Brainstem auditory-evoked potential (BAEP) examinations were performed in 15
      patients with long-standing type-1 diabetes mellitus (DM). Cardiovascular reflex
      tests were applied for assessment of autonomic neuropathy. The aim of our
      investigation was to compare the BAEP results of this patient group with controls
      and to look for a possible correlation between the alteration of the auditory
      brainstem function and the cardiovascular autonomic neuropathy. Analysis of the
      latencies (waves I, II, III and V) and the inter-peak latencies (waves I-III and
      I-V) of BAEPs revealed a significant difference between diabetics and healthy
      controls. The amplitudes of waves I, III and V were definitely lower in
      comparison with those of healthy controls. A positive correlation was observed
      between the overall autonomic score and the latencies (waves III and V) and inter
      peak latencies (waves I-III and I-V). These data support the hypothesis that long
      standing DM and diabetic neuropathy might be related as a cause of certain
      dysfunctions of the central auditory pathways.

PMID- 11318454
TI  - Carhart notch effect in otosclerotic ears measured by electric bone-conduction
      audiometry.
AB  - The Carhart notch is an elevation in the middle-frequency bone-conduction
      threshold of an ear with clinical otosclerosis. The study population consisted of
      138 patients with clinical otosclerosis. Conventional air-conduction (AC) and
      bone-conduction (BC) and electric bone-conduction (EBC, with Audimax 500
      audiometer) thresholds were measured 2 weeks before and 7 months after stapes
      surgery. The EBC thresholds were converted from mA values to dB SPL to compare
      the results obtained with the different methods. The mean differences in the BC
      thresholds before and after the operation were 3.2 dB (95% CI 1.9-4.6) at 1 kHz
      and 7.6 dB (95% CI 6.1-9.1) at 2 kHz. The mean differences in the EBC thresholds
      were 5.4 dB (95% CI 3.8-6.9) at 1 kHz and 5.3 dB (95% CI 3.4-7.1) at 2 kHz. Thus,
      both methods showed a distinct Carhart notch effect.

PMID- 11318455
TI  - Finnish speech in noise test: long-term reproducibility.
AB  - A computerized adaptive Finnish speech in noise test was developed recently. As
      part of the test's evaluation process the long-term stability of speech
      recognition threshold in noise (SRTN) was determined. The non-operated ears of
      164 stapes surgery patients were assessed preoperatively and at 1, 7 and 19
      months postoperatively. Short-term and long-term repeatability were equal. The
      absolute intraindividual differences were 1.5 dB on average.

PMID- 11318456
TI  - The Finnish speech in noise test for assessing sensorineural hearing loss.
AB  - A computerized adaptive Finnish speech in noise test was developed recently. As
      part of the test's evaluation process 172 patients with sensorineural hearing
      loss including 20 normally hearing subjects were measured using pure-tone
      audiometry, speech recognition threshold in noise (SRTN) test and conventional
      speech audiometry without background noise. As anticipated, sensorineural hearing
      loss yielded an elevation of SRTN although individual differences were
      considerable. The SRTN test was accurate as the absolute difference between
      individual repeated SRTNs was, on average, 1.5 dB (SD 1.5 dB) when the range of
      possible test values is from approximately -12 to +20 dB. On average, the
      learning effect was 0.5 dB.

PMID- 11318457
TI  - Hearing in the elderly: a test protocol and preliminary results.
AB  - Hearing deteriorates with age. ISO 7029 (2000) presents data on hearing threshold
      as a function of sex and age up to 70 years. There is a need for an extension of
      these data beyond 70 years. There is also a need for testing the central
      component of hearing in the elderly. A test protocol was established, and groups
      of subjects aged 60 to > or = 90 were selected. After a questionnaire and an ear
      examination, the following tests were performed: air-conduction pure-tone
      audiometry in the frequency range of 125-16 kHz, tympanometry, speech recognition
      score in quiet conditions, transient evoked otoacoustic emissions (TEOAE) and
      cognitive cortical evoked potentials (MMN, P300, N400). Preliminary tests showed
      the expected age-related reduced hearing sensitivity as seen from the pure-tone
      audiograms, a lower speech recognition score in the oldest subjects, lack of
      TEOAE and poor cognitive responses in the elderly. Statistical data will be
      developed based on the complete material of around 400 subjects.

PMID- 11318458
TI  - On the construction of a Finnish audiometric sentence test.
AB  - To respond to the demands of clinical practice and the needs of rehabilitation, a
      Finnish audiometric sentence test is being developed. The test consists of 10
      sets of 10 sentences, each set serving as an independent test. The test is scored
      by words (50 per set). Homogeneity between the sets was guaranteed by a number of
      linguistic and phonetic criteria, controlled by using the Virko Sentence
      Analyzer, a programme especially constructed for the purpose. Recognition tests
      for the validation of the sentence sets were made with young normally hearing
      adults (n = 70; age group 18-25 years). Psychometric recognition properties of
      the test are described. The selection process of the final 10 sentence sets is
      illustrated.

PMID- 11318459
TI  - Ways to promote a noise control programme.
AB  - The purpose of this study was to find out the proper ways to promote and to start
      a noise control programme in small and medium size industries. The situation of
      the noise control programme was inspected in four industrial enterprises. The
      noise exposure and the noise sources were studied and recommendations for noise
      reduction were given. The information concerning the noise control programme and
      noise levels was given to the personnel. How the noise control programme was
      started in the companies and which were the best ways to promote the programme
      were examined after 1 year. Noise reduction work was carried out in companies
      during the past year and new ideas were awaiting investment. The systematic noise
      control programme was not written on paper or connected to a risk management
      programme. The lack of proper models of a programme, lack of time and knowledge
      of easy means to reduce the noise were reasons for missing noise control
      programmes. The best ways to push up the noise control programme were to give
      information and examples of the programme. The EU-directive concerning machines
      and its noise information was a help in the noise reduction work connected with
      new investments.

PMID- 11318460
TI  - Active noise reduction in aviation helmets during a military jet trainer test
      flight.
AB  - Cockpit noise measurements were carried out in a two-seat jet trainer. For the
      continuous time and frequency analyses a two-channel tape-recording system was
      constructed of two miniature microphones connected through an amplifier to a
      digital tape-recorder. The analysed and averaged noise exposure including radio
      communication was 80-81 dB when the ANC system was on and 84-89 dB when the ANC
      system was off. For the conventional flight helmet the same noise exposure was 86
      dB, and the noise exposure in the cockpit was 104-106 dB. The effect of the ANC
      system on the averaged noise exposure (L(Aeq8min)) was an improvement of 4-8 dB
      over the noise attenuation of the same helmets when the ANC system was off. Both
      ANC systems worked properly during the test flights. No severe ringing or voice
      circulation was found except during extreme vibration.

PMID- 11318461
TI  - A hospital based universal neonatal hearing screening programme using click
      evoked otoacoustic emissions.
AB  - Since 1997 a hospital-based universal hearing screening programme (Milan
      Programme) has been carried out at the Neurophysiopathology Unit of the
      Mangiagalli Clinic in Milan, for the early identification of hearing loss in
      neonates (5650 well babies, 749 newborns from the Neonatal Pathology Unit (NPU)
      without risk for hearing loss and 118 newborns at risk for hearing loss). As a
      result, considering the well baby population, three pathological neonates (one
      profound bilateral and two unilateral hearing loss) were identified. Three
      additional cases were found among the NPU newborns, whereas 16 cases with
      bilateral and 11 with unilateral hearing loss were found among the at-risk
      babies.

PMID- 11318462
TI  - The efficacy of medication on tinnitus due to acute acoustic trauma.
AB  - Seventy-two young males suffering from acute acoustic trauma with tinnitus due to
      gunshots were included prospectively in the study. Forty of the subjects had the
      left ear affected, four the right ear and the remaining 28 sustained bilateral
      acoustic traumas. The mean time of admission after onset of symptoms was 28 days
      (5-88 days). The subjects were randomly categorized into three groups: group A
      received trimetazidine, prednisolone and complex B vitamins; group B were treated
      only with trimetazidine; and group C received prednisolone and complex B
      vitamins. At 3-month follow up, tinnitus had been completely eradicated in only
      eight subjects and had in 17. No statistically significant difference was found
      between the three groups concerning improvement of tinnitus. However, it was
      found that early admission predisposed towards better prognosis. The degree of
      hearing improvement after medication did not seem to correlate with the relief of
      tinnitus.

PMID- 11318463
TI  - Tinnitus of vestibular origin.
AB  - During the exercises devised by Seymont and/or Epley for rehabilitation of benign
      paroxysmal positional vertigo, we observed that the accompanying tinnitus
      disappeared immediately in some patients. Following this observation and using
      the same maneuver, we examined two groups of patients. The first group included
      86 patients with continuous tinnitus, or tinnitus in specific head/body
      positions. whose origination was associated with recent vestibular
      symptomatology. The second group included 100 patients with positional tinnitus,
      but without any vestibular disorder. Ages ranged between 35 and 78 years and
      gender distribution was 114 females and 72 males. It was shown that 29 patients
      in the first group (33.2%) and 18 patients in the second group (18%) could be
      released from their tinnitus. Eleven patients in the first group (12.7%) and 7
      patients in the second group (7%) noticed a reduction of their tinnitus. These
      results show that in the above-mentioned cases relief of vestibular symptoms
      alleviates the tinnitus. This could be mediated by a reduction in autonomic
      activity, known to affect tinnitus.

PMID- 11318464
TI  - Experiences in the treatment of patients with tinnitus and/or hyperacusis using
      the habituation method.
AB  - The purpose of this study was to summarize the results achieved by patients with
      tinnitus and/or hyperacusis during the Tinnitus Retraining Therapy. One hundred
      cases, out of 516 patients registered until January 1999 at the Tinnitus and
      Hyperacusis Management Clinic, Warsaw, Poland, were examined. The patients have
      been treated for at least 10 months but not longer than 1 year. A questionnaire
      specially prepared for this program was used to assess the results. In the group
      of 100 cases, the results after a minimum of 10 months' therapy are different in
      each category but they show a significant improvement in about 70% of cases.

PMID- 11318465
TI  - Impairments of vestibular system in infants at risk of early brain damage.
AB  - Children with early brain damage often present with balance disorders. We
      evaluated the vestibular apparatus function in 110 infants at risk of brain
      lesions. Our study confirmed a statistically significant correlation between
      vestibular apparatus dysfunction and the degree of neurological risk. Early
      recognition of vestibular disorders preconditions adequate rehabilatation and
      supports the acquisition of motor skills.

PMID- 11318466
TI  - Low birth weight as a risk factor of hearing loss.
AB  - The purpose of this study was the audiological evaluation of low birth weight
      children as well as to investigate any possible relation between very low birth
      weight and the associated risk factors and the subsequent hearing loss. A group
      of 110 children was examined audiologically. The prenatal, perinatal and
      postnatal risk factors were related to the audiological diagnosis. Depending on
      the patient's age, audiological examination consisted of auditory brainstem
      responses, pure tone audiometry and impedance audiometry. The presence of more
      than two risk factors in the perinatal and postnatal categories was connected
      with profound hearing loss in later life. No such relation was found with the
      cumulation of the prenatal risk factors. In our material the greatest risk of the
      acquired profound hearing loss and deafness occurring in low birth weight
      children was connected with the general physical status of the neonates and the
      treatment programme in the neonatal intensive care unit.

PMID- 11318467
TI  - Project of the countrywide data collecting system for neonatal hearing screening
      programme in Poland.
AB  - Neonatal hearing screening is becoming a standard of care in increasing number of
      hospitals and outpatient departments in Poland. A project of central data
      collecting system applicable to a neonatal hearing screening programme has been
      elaborated as a preparation to introducing a countrywide screening programme. The
      data collecting system will be based on the currently existing central system for
      the registration of neonatal screening tests for metabolic diseases. Data on risk
      factors for hearing loss and hearing screening test results will be collected. A
      central data collecting system for a neonatal hearing screening programme will
      increase the efficiency of the screening programme and facilitate epidemiological
      studies.

PMID- 11318468
TI  - Cochlear dysfunction and diabetic microangiopathy.
AB  - The aim of this study was to evaluate the cochlear micromechanics in type 1
      diabetic patients and to compare these findings with diabetic microvascular
      complications (retinopathy and nephropathy). Cochlear activity was evaluated by
      recording 2f1-f2 DPOAE. DPOAEs were performed using an ILO92 Otodynamics Ltd
      Analyser. DPOAEs were measured in 42 normally hearing IDDM patients aged between
      21 and 42 years, and 33 age-and sex-matched non-diabetic control subjects. IDDM
      patients were divided into two groups: 17 patients without microangiopathy and 25
      with microangiopathy. Microangiopathy was evaluated with ophthalmoscopy and 24
      hour albumin excretion rate into urine. Both groups (diabetic and control) had
      normal and undifferentiated results in tonal and impedance audiometry. The mean
      amplitudes of various DPOAEs were significantly reduced in the diabetic groups
      (with and without microangiopathy) compared with control subjects. No correlation
      was found between diabetic microvascular complications and DPOAE amplitudes
      reduction. Our results indicate the existence of an alteration in cochlear
      micromechanics in diabetic patients with microangiopathy as well as in patients
      without microangiopathy. The lack of significant correlation between the degree
      of microvascular complications in the retina or kidneys and DPOAEs amplitude
      reduction suggest that the impaired functional properties of the outer hair cells
      are probably caused by early metabolic complications in diabetes (among other
      things non-enzymatic glycation related to hyperactivity of free oxygen radicals)
      and not directly by diabetic microangiopathy.

PMID- 11318469
TI  - Incidence of hearing loss among children presented with speech-language delay.
AB  - Infants' first attempts to communicate with their environment begin shortly after
      birth. However, real words appear by age of 12-15 months. Any delay in expressing
      their needs verbally beyond this age is defined as speech delay and may be
      associated with a variety of pathological conditions. The aim of this study is to
      investigate the incidence of hearing impairment in those children presented with
      speech delay. Ninety-one speech-delayed children were audiologically assessed
      between March 1993 and March 1995. In 25 out of 91 children (27.4%) a moderate to
      severe hearing loss was detected, either sensorineural or conductive. The
      increased incidence of hearing impairment found in this group mandates a thorough
      hearing evaluation for any case of speech-language delay.

PMID- 11318470
TI  - Effects of tinnitus retraining therapy (TRT) for patients with tinnitus and
      subjective hearing loss versus tinnitus only.
AB  - The patients with tinnitus and/or hyperacusis undergoing an 18-24 month period of
      TRT are divided into five categories of treatment. Different types of counselling
      and sound therapy are used in each category. Selection of patients into a
      specific category depends on such factors as: hyperacusis, subjective hearing
      loss and long-lasting effect of noise on tinnitus. The 108 cases were evaluated
      After 1 year of treatment. The results of therapy of 40 patients with tinnitus
      and subjective hearing loss (category II) were compared with the results of
      therapy of patients with tinnitus only (categories 0 and I). A special
      questionnaire, answered before and during the treatment, was used to assess the
      results. Our data indicate significant improvement in about 70% of patients with
      tinnitus only and in about 90% of patients with tinnitus and subjective hearing
      loss after one year of therapy.

PMID- 11318471
TI  - HI-SIMv1.0--towards the virtual reality of hearing impairments.
AB  - The virtual reality of hearing impairments has obvious practical applications in
      areas such as audiology, speech therapy and hearing aid technology and serves as
      an informational tool for the family members of the hearing impaired. To simulate
      hearing impairment, a CD-ROM with filtered speech material accessible through a
      graphical user-interface was produced; the user-interface was created with
      standard multimedia tools. The CD-ROM, HI-SIMv1.0, intended as an interactive
      educational tool, offers a virtual experience of the effects of a selection of
      common types of hearing impairment. The options available in this simulation
      include grade of hearing impairment, audiometric configuration and the type and
      level of background noise. Word recognition scores can be computed for standard
      Finnish audiometric material.

PMID- 11318472
TI  - The hearing system in newborns from the Upper Silesia. Assessment of TEOAE
      depending on selected parameters of delivery disorders.
AB  - Transient evoked otoacoustic emission (TEOAE) is an accepted test for screening
      of the cochlea function in newborns. In this study 300 newborns was tested using
      TEOAE, as well as analysing such parameters as birth weight, Apgar scale,
      bilirubinaemia. The study indicated the tendency of TEOAE to decrease in newborns
      with low birth weight and low Apgar scores. Hyperbilirubinaemia seems to have an
      influence on cochlea function monitored by TEOAE, especially if there were
      simultaneously low Apgar scores. A similar tendency, although slightly stronger,
      was observed in the preterm newborn group. TEOAE seems to be a good method of
      recording the negative influence on the cochlea activity such factors as low
      birth weight and asphyxia. Hyperbilirubinaemia with asphyxia acts upon the
      cochlea similarly. All these tendencies were observed more strongly in the
      preterm newborn group. It is concluded that TEOAE analysis demonstrated its
      utility as a screening test assessing the hearing state in newborns, additionally
      the associations of cochlea activity was found with a few parameters of delivery
      disorders.

PMID- 11318473
TI  - Development of an Arabic battery for remediation of selective auditory attention
      disorder in children.
AB  - A battery of Arabic speech material was developed for remediation of selective
      auditory attention disorder (SAAD) in children and standardized on 40 normal
      children aged from 6 to 12 years. This battery included: the Word Intelligibility
      by Picture Identification (WIPI) test, newly developed sentences for speech
      discrimination in noise, bisyllabic words and monosyllabic words. The tests were
      recorded against a background noise of either multitalker babble or stories.
      Variables affecting the results of the new battery, namely age, type of speech
      material and type of background noise, were studied. A significant positive
      correlation was found between the age of the child and the test scores. The WIPI
      test was the easiest test, giving the highest scores. The monosyllabic words test
      was the most difficult, yet normal children gave mean scores around 92%. The type
      of background noise showed a non-significant effect on the test scores. Results
      of two cases with SAAD are also presented.

PMID- 11318474
TI  - Towards a universal newborn hearing screening.
AB  - Hearing loss is a common problem which, if remaining undetected during early
      childhood, could affect the patient's linguistic and mental abilities
      permanently. Although recommended, mass hearing screening has so far been
      problematic or even impossible due to several reasons. The available otoacoustic
      emission devices appear to be effective tools for universal hearing screening.
      The aim of this study is to evaluate the reliability and practicability of a new
      device for recording click-evoked otoacoustic emissions (cEOEs) on a pediatric
      population. Sixty children aged between 6 days and 14 years were evaluated
      audiologically both by auditory brainstem responses (ABR) and otoacoustic
      emissions. The latter were obtained by using the well-known ILO88v3.92
      otoacoustic analyser and a new, portable device ('Echocheck', Otodynamics Ltd,
      UK). Sensitivity and specificity of cEOEs recorded by 'Echocheck'was found to be
      93% and 91%, respectively, when compared to ABR results. Additionally,
      'Echocheck' recordings were proved to be much easier to perform, needing
      considerably less time in comparison with those of the ILO88 system. In our
      opinion, 'Echocheck' as well as all similar portable devices--screeners--may
      represent a much-desired solution for implementing universal hearing screening
      programmes.

PMID- 11318475
TI  - Progression of sensorineural hearing impairment in aided and unaided ears.
AB  - The possibility of "adult onset auditory deprivation" has been proposed as a
      condition of extensive deterioration of speech discrimination in unaided ears.
      Pure tone thresholds and speech discrimination were studied in a follow-up
      examination on 500 patients using hearing aids unilaterally. The follow-up time
      ranged from 5 to 24 years. In average the same amount of deterioration was
      obtained in both ears. Deterioration in pure tone thresholds increased after the
      age of 80 years and speech discrimination after 65 years respectively. The
      results obtained gave no support to the concept of adult onset auditory
      deprivation in unaided ears.

PMID- 11318476
TI  - Audiological assessment of unilateral deafness.
AB  - Unilateral deafness constitute medical (aetiological diagnosis, treatment,
      hearing aid fitting) and social problems (no certification of disability).
      Following audiological examinations were performed in the study: pure tone
      audiometry (PTA), impedance audiometry, auditory brainstem responses (ABR),
      otoacoustic emissions (OAE), as well as balance, taste, examinations and electric
      sensitivity of the acoustic nerve. In cases of tinnitus the parameters of its
      character were done. All of our patients underwent X-ray investigations, i.e. ear
      X-ray by Schuller and Stenvers methods, computerized tomography or magnetic
      resonance imaging. In some cases phoniatric and logopaedic examinations were
      performed. For aetiological diagnosis electrophoresis and immunological test (IgG
      and IgM against mumps) were carried out. The results were presented in two groups
      of patients with sudden and those of long lasting progressive unilateral
      deafness. Some of the patients were pharmacologically treated before the
      evaluation. It is concluded that the statistic analysis could be a basis for the
      management and prognosis of the unilateral deafness.

PMID- 11318477
TI  - Speech processing strategy preferences among 55 European CLARION cochlear implant
      users.
AB  - This multicentre study investigates the preference and performance of a group of
      55 adult CLARION cochlear implant users with the choice of simultaneous analogue
      stimulation (SAS) and continuous interleaved sampler (CIS) strategies during the
      first 3 months of implant use. Subjects were programmed with both strategies and
      instructed to use each of the two strategies in daily life to ascertain
      preference. Subjects were tested in both strategies with open-set sentence
      materials, auditory alone, at 2, 6 and 12 weeks after the initial programming
      session. Questionnaires were completed with preference ratings being recorded for
      the two strategies: 25% of subjects preferred SAS and 75% CIS. Subjects performed
      better in their strategy of choice. Preferences were set very early on in the
      process and did not change. Factors influencing preference are discussed.
      Offering the choice of fundamentally different strategies improves both
      individual and group performance.

PMID- 11318478
TI  - Speech perception results--the first 10 years of a cochlear implant program.
AB  - Long-term speech perception test results for prelingually deaf children were
      compared with those of postlingually deafened adults, both groups having
      undergone cochlear implant at our Center. Average open-set score results of
      adults were similar to those of the children. However, some qualitative
      differences were demonstrated on the perception of phonological contrasts between
      the groups.

PMID- 11318479
TI  - Results of total deafness treatment in young pre- and postlingually deafened
      children.
AB  - Developing a cochlear implant program is one of the most difficult problems we
      need to solve concerning young children. Application of cochlear implants to this
      group of patients gives hope for better speech and language development than
      using conventional hearing aids. Children comprise approximately 40% of all
      implanted patients at the Institute of Physiology and Pathology of Hearing in
      Warsaw. They are provided with different types of cochlear implants, 16 of which
      are included in the international comparative study EARS (Evaluation of Auditory
      Responses to Speech). In this paper results are presented of auditory speech
      perception in pre-, peri-and postlingual children using the multichannel cochlear
      implant systems COMBI 40 and 40+. All the children were regularly evaluated
      following the EARS procedure with a number of perception tests. Monitoring of
      auditory perception development is fundamental and allows prognosis of speech and
      language development in children.

PMID- 11318480
TI  - Speech perception and functional benefit after multichannel cochlear
      implantation.
AB  - This study was done to investigate the effect of a multichannel cochlear implant
      on speech perception and the functional benefit of cochlear implantation in
      Finnish-speaking postlingually deafened adults. Fourteen subjects were enrolled.
      Sentence and word recognition were studied with open-set tests auditorily only.
      One year after implantation, the listening performance was assessed by case
      histories and interviews. Before implantation for subjects with a hearing aid,
      the mean recognition score was 38% for sentences and 17% for words. One year
      after switching on the implant, the mean recognition score was 84% for sentences
      and 70% for words. Before implantation, the majority of the subjects were not
      aware of environmental sounds and only a few were able to recognize some
      environmental sounds. One year after switching on the implant, the majority of
      the subjects were able to use the telephone with a familiar speaker. All the
      subjects were able to recognize speech auditorily only and had thus gained good
      functional benefit from the implant.

PMID- 11318481
TI  - Cochlear implant patients and quality of life.
AB  - During the last two decades, cochlear implants have been available for profoundly
      hearing-impaired patients who do not benefit from conventional hearing aids. The
      quality of life of these implantees has not been extensively studied, and has not
      been studied at all in Finland. To assess their quality of life, the Nottingham
      Health Profile questionnaire was sent to all adult implanted patients in Finland.
      Implantees tended to have more favourable average pain, emotional reaction and
      mobility indexes in each age group studied than the average population. Social
      isolation seemed to be more common in the youngest and oldest age groups of
      implantees. Apparently, implantees are physically healthier than the average
      population. However, a bias caused by the strict selection of implant candidates
      cannot be excluded.

PMID- 11318482
TI  - The effect of a multichannel cochlear implant on phoneme perception.
AB  - This study was done to investigate the effects of a multichannel cochlear implant
      on phoneme perception in Finnish-speaking postlingually deafened adults. Phoneme
      recognition was studied with 100 prerecorded nonsense syllables (open-set)
      presented at 70 dB SPL, auditorily only, in a free-field situation. Ten subjects
      were tested before implantation both with and without a hearing aid (HA), and 3,
      6 and 12 months after switching on the implant. Before implantation without a HA,
      the subjects did not recognize vowels, consonants or syllables. Four of the
      subjects used a HA before implantation, and the mean recognition scores of these
      subjects were 34% for vowels, 28% for consonants and 13% for syllables. One year
      after switching on the implant, the mean recognition scores were 77% for vowels,
      66% for consonants and 46% for syllables. According to phonological analysis
      vowels appear to be easier to perceive than consonants during the first stage
      after multichannel cochlear implantation.

PMID- 11318483
TI  - Cochllear implants and GSM phone.
AB  - Use of a telephone and GSM phones, in particular, was assessed by means of a
      postal interview sent to all adult Finnish implantees. The response rate was very
      high (87%). Fifty-one of the 61 respondents used a telephone and 27/61 also used
      a mobile phone, usually a digital phone. Two GSM phone models from Nokia (3110
      and 6110) were tested with three different cochlear implant systems used by nine
      patients. Definite differences between the processors were found. Nucleus Spectra
      (two implantees) could not be used with any of the GSM phones under any test
      condition. Nucleus SPrint was incompatible with both GSM phone models in a poor
      field, while GSM phone model 6110 could be used in a good field. The Med-El Combi
      40+ processor was compatible with both GSM models tested under any condition.

PMID- 11318484
TI  - Hearing aid fitting procedures--state-of-the-art and current issues.
AB  - The increasing degree of sophistication in hearing aid technology calls for
      appropriate fitting strategies, as otherwise hearing aid users cannot receive the
      full benefit from the most modern technological achievements. This paper
      describes the state of the art in hearing aid fitting procedures and offers a
      look into possible future developments. Currently, threshold-based fitting
      formula compete with loudness- and sound-based fitting procedures. Whereas
      threshold-based approaches are straightforward and timesaving, they do not
      consider loudness growth and the sound preferences of the listener. On the other
      hand, loudness- and sound-based procedures do take these aspects into account,
      but they are time consuming and it is not yet proven that they provide higher
      benefit for the end user. This may be due to the fact that either there is
      actually no extra benefit or more likely that the evaluation tools or study
      designs have to be improved. Concerns about how to fit more advanced future
      hearing instruments seem to be inappropriate, as an analysis of possible future
      signal processing algorithms shows that they probably do not need extra fitting
      to the individual hearing impairment but rather need optimization according to
      the acoustical environment.

PMID- 11318485
TI  - A fitting strategy for digital hearing aids based on loudness and sound quality.
AB  - In order to find an adequate fitting strategy for digital compression hearing
      aids a combination of two interactive fitting strategies was developed, one of
      these based on frequency specifice loudness (ScalAdapt) and the other based on
      overall loudness and on sound quality (Cambridge Procedure). This new fitting
      strategy was tested against the sound and overall loudness based strategy and
      against a prescriptive fitting strategy in a 2-weeks field test with
      questionnaires and in laboratory measurements, subjectively as well as
      objectively. With six sensorineural hearing impaired participants no
      straightforward results were achieved. Additionally, the different testing
      procedures indicate (in tendency) different fitting strategies to be superior.
      More subjects will have to be tested and innovative evaluation methods have to be
      considered.

PMID- 11318486
TI  - Multi-microphone technology for severe-to-profound hearing loss.
AB  - In this study the potential benefit of hearing instruments with multi-microphone
      technology was investigated in laboratory and in field tests for users with
      severe-to-profound hearing loss. Twenty-one experienced hearing aid users were
      fitted with high-power multi-microphone hearing instruments (Phonak PowerZoom P4
      AZ). The following evaluations were performed: (i) adaptive speech test (SRT for
      HSM sentence test) in quiet and in noise with their own instrument and the test
      instrument in the omnidirectional (basic program) and directional mode (party
      noise profound+zoom algorithm). (ii) Paired comparisons of loudness, sound
      quality and speech intelligibility for both the omni and zoom program. (iii)
      Questionnaires on satisfaction and self-assessment of communication in different
      listening conditions (Oldenburg Inventory). Only 10 subjects achieved 50% correct
      (SRT) on the sentence test in noise (speech 0 degrees/noise 180 degrees) with
      both their own instrument and the test instrument in the omnidirectional mode.
      However, 15 subjects succeeded in the SRT measurement in the directional mode.
      The average SRT improvement of the directional over the omnidirectional mode was
      13.7 dB. Loudness was judged 'medium loud' for both listening programs. Sound
      quality and intelligibility were rated significantly better for the zoom program.
      Compared to their own instrument users' satisfaction with the test instrument was
      significantly higher, especially in noisy listening situations.

PMID- 11318487
TI  - Benefit of a digital feedback suppression system for acoustical telephone
      communication.
AB  - Because hearing instruments have traditionally performed poorly during acoustical
      telephone use, the benefit of using a Digital Feedback Suppression (DFS) system
      for acoustical telephone communication was evaluated. For this purpose a special
      speech test based on the method and material of the Oldenburg Sentence Test was
      developed, presenting the speech signal via a telephone receiver. The correct
      coupling of the receiver and the hearing aid was monitored by means of a probe
      microphone. The word score was determined for two different settings of the
      hearing aid: (1) DFS activated (2) DFS deactivated. The difference in word score
      between these two conditions is an indication of the benefit provided by the DFS
      system. For almost all subjects, speech recognition at the telephone could be
      improved using the DFS system. This is a significant contribution in increasing
      end-user overall satisfaction with hearing aids.

PMID- 11318488
TI  - Examples of implemented neonatal hearing screening programs in Austria.
AB  - In order to improve early detection of congenital permanent childhood hearing
      impairment the Austrian ENT society recommended in 1995 that universal neonatal
      hearing screening be introduced ("Millstatter Concept"). Coverage is presently
      about 67% for full-term healthy neonates and 86% for neonates from intensive care
      units. For maternity units, referral rates between 1% and 3.7% have been reported
      (2.7-15% for intensive care units). The results of the screening test and follow
      up in cases of failure have been documented in 37,543 neonates. Of this
      population, 91 infants (2.4 per 1000) showed bilateral permanent hearing loss. In
      these children intervention and management of the family started within the first
      months of life. These results justify the effort involved in introducing
      universal neonatal hearing screening.

PMID- 11318489
TI  - Comparison of two digital hearing instrument fitting strategies.
AB  - Two different hearing instrument fitting strategies were compared in the
      laboratory and in a field test with regard to the benefit for hearing aid users
      and their satisfaction with the fitting. DSL [input/output (i/o)] fittings based
      on hearing threshold and uncomfortable levels for the subject were evaluated vs a
      prescriptive fitting method based on unaided loudness scaling. Twenty-one
      subjects were fitted diotically with both fitting strategies implemented in a
      digital hearing instrument (Siemens Prisma). The patients tested both fitting
      strategies sequentially in a 4 + 4-week field trial using a crossover study
      design. Speech recognition threshold measurements, sound quality ratings and
      paired comparisons of sound quality were performed for all conditions (unaided,
      DSL[i/o] fitting and loudness-based fitting). In addition, subjective benefit and
      preference were assessed with questionnaires. Speech audiometry did not reveal
      significant differences between the two fittings. DSL[i/o] fittings showed
      superior results in most sound quality tests and in the self-assessment of
      communication abilities while the loudness-based approach was slightly preferred
      in noisy environments. The results seemed to be influenced by the higher gain
      predicted by DSL[i/o]. This study provides no evidence that effort spent on
      loudness scaling leads to improved fitting results.

PMID- 11318490
TI  - User tests with the multi-mode compression architecture.
AB  - The Multi-Mode Compression (MMC) architecture is a new system for better speech
      understanding, listening comfort and user acceptance. This study reports on the
      user tests that have been performed to verify the benefits of the concept and the
      quality of the fitting process for the individual hearing impaired. The study
      concentrates on the 4-channel version of a new series of digital instruments with
      this MMC architecture.

PMID- 11318491
TI  - Computerized in-situ test for bone conduction hearing aids.
AB  - Conventionally, bone-conduction (BC) hearing aids are tested with skull simulator
      devices and the individual adjustments are reliant on psychoacoustic free-field
      audiometry. Here we present a novel PC-based system for in situ measurements of
      BC hearing aids. With the presented system, we are able to measure the hearing
      aid induced skull vibrations in relation to the individual BC hearing threshold
      at given frequencies. According to the preliminary measurements, the vibration
      levels are relatively low but the system is sensitive enough for relevant
      measurements.

PMID- 11318492
TI  - Objective assessment of hearing aid use.
AB  - Hearing aid use was assessed using both objective (time recorded in the memory of
      the hearing aid) and subjective methods (interview and patient diary) in a
      clinical series of consecutive adult female and male Finnish and Norwegian
      hearing aid candidates (n = 84). The median study time was 34 days (minimum 21,
      maximum 73). Over a third of the subjects used their hearing aid for less than 4
      hours a day according to an objective assessment. Both of the subjective methods
      tended to overestimate the use. This preliminary study shows that an objective
      assessment of hearing aid use is needed and the subjective methods must be
      validated.

PMID- 11318493
TI  - The Finnish speech-in-noise test in MELAS mutation and other sensorineural
      hearing impairments.
AB  - A computerized adaptive Finnish speech-in-noise test has recently been developed.
      The purpose of the present study was to measure speech recognition thresholds in
      noise (SRTN) in patients with sensorineural hearing impairment (SNHI) caused by
      mitochondrial mutation [mitochondrial myopathy, encephalopathy, lactic acidosis
      and stroke-like episodes (MELAS)] and in patients with SNHI from other causes and
      to compare them with those in normal hearing controls. SRTN differed
      significantly between controls and the patients with SNHI from other causes and
      between controls and the MELAS group, but not between SNHI patients and the MELAS
      group. Hearing in a noisy environment seems to be as impaired in MELAS patients
      as in patients with SNHI from other causes, in spite of the possible coexisting
      defects in the central nervous system.

PMID- 11318494
TI  - Autosomal dominant midfrequency hearing impairment.
AB  - At present, 48 different gene loci have been localised and nine gene mutations
      have been characterised for non-syndromic hearing impairment. We have identified
      a large five-generation family with mid-and high-frequency hearing impairment.
      Family members were considered to be affected only if they had bilateral
      sensorineural hearing loss below the 90th percentile of an age and sex-dependent
      control audiometric curve of ISO class B. The inheritance of hearing impairment
      was autosomal dominant. Of seven affected individuals, six were females and one
      was male. The hearing loss among affected family members was bilateral,
      sensorineural and varies from mild to moderate. The type of audiogram was U
      shaped. Genetic linkage studies are in progress and our preliminary data show
      exclusion in chromosome 6, chromosome 11 and chromosome 19 in already known loci
      for midfrequency hearing impairment. This means, we are mapping a novel locus for
      autosomal dominant midfrequency hearing impairment.

PMID- 11318495
TI  - Educational needs of speech and language therapists in the field of audiology.
AB  - Speech and language therapists have rather diverse educational backgrounds
      globally. Their qualifications vary from a 1 to 2-year diploma or certificate
      programme in a non-university educational setting, to a 6-year university
      graduate education. Although speech and language therapy is generally considered
      an interdisciplinary profession, both in education and in clinical practice, in
      some countries the main emphasis may still be on special education, medicine
      (mainly medical audiology) or, because of a joint qualification, psychology. This
      article discusses the requirements for audiological education in proper
      assessment and (re)habilitation of hearing impairments. Future challenges of both
      the profession and the discipline of speech and language therapy are also
      highlighted.

PMID- 11318496
TI  - Experiences of otoneurological expert system for vertigo.
AB  - We have developed an OtoNeurological Expert system (ONE) to aid the diagnostics
      of vertigo, to assist teaching and to implement the database for research. The
      database contains detailed information on the patient history, signs and test
      results necessary for the diagnostic work with vertiginous patients. The pattern
      recognition method was used in the reasoning process. Questions regarding
      symptoms, signs and test results are weighted and scored for each disease, and
      the most likely disease is recognized from the defined disease profiles.
      Uncertainties in reasoning, caused by missing information, were solved with a
      method resembling fuzzy logic. We have also applied adaptive computer
      applications, such as genetic algorithms and decision trees, in the reasoning
      process. In the validation the expert system ONE proved to be a sound decision
      maker, by solving 65% of the cases correctly, while the physicians' mean was 69%.
      To improve the expert system ONE further, a follow-up should be implemented for
      the patients, to ease the diagnostic work of some difficult diseases. The six
      diseases were detected with high accuracy also with adaptive learning methods and
      discriminant analysis. An expert system is a practical tool in otoneurology. We
      aim to construct a hybrid program for the reasoning, where the best reasoning
      method for each disease is used.

PMID- 11318497
TI  - A proposal for a model to calculate hearing disability.
AB  - The present paper presents an alternative method to calculate hearing disability.
      As opposed to existing models to calculate hearing disability, the present method
      is not just based on the pure-tone audiogram. Hearing activities playing an
      important role in daily listening are taken into account: detection of sounds,
      distinction of sounds, intelligibility in quiet and in noise, auditory
      localization. Psycho-acoustical tests to measure each of these activities are
      described. Test scores are used to calculate overall hearing disability. A
      comparison is made between the present model and the method of the American
      Medical Association (AMA). Calculations are based on theoretical cases only.
      Further study has to be undertaken to verify the calculations by examining the
      scores of real cases to improve the validity and internal consistency of the
      present model.

PMID- 11318498
TI  - Application of artificial intelligence in audiology.
AB  - In this paper, machine learning methods based on artificial intelligence theory
      are applied to the computer-aided decision making of some otoneurological
      diseases, for example Meniere's disease. Three methods explored are decision
      trees, genetic algorithms and neural networks. By using such a machine learning
      method, the decision-making program is trained with a representative training set
      of cases and tested with another set. The machine learning methods are useful
      also for our otoneurological expert system, One, which is based on a pattern
      recognition approach. The methods are able to differentiate most of the cases
      tested between the six diseases included, provided that a sufficiently large
      training set is available.

PMID- 11318499
TI  - Influence of pH and sodium chloride on selected functional and physical
      properties of African breadfruit (Treculia africana Decne) kernel flour.
AB  - African breadfruit seeds were cleaned, parboiled (98 degrees C) for 15 min,
      drained and dehulled. The kernels were sun-dried, then milled and sieved into
      flour. Nitrogen solubility (NS), water absorption capacity (WAC), emulsion
      activity (EA), viscosity, foaming and emulsifying properties of the flour were
      determined as functions of pH and NaCl concentration. The NS was pH dependent
      with a minimum at pH 4 and maximum at pH 10. The flour also exhibited minimum and
      maximum foam capacity at pH 4 and 10, respectively. The minimum emulsion activity
      was at pH 4, a value which increased from 7-16% at pH 12. The addition of NaCl at
      concentrations of 0.2 to 0.4 M improved WAC, NS, foaming and emulsion properties
      of the flour. Sodium chloride enhanced NS of the flour at pH 4-6 and EA at pH 2
      8. The EA at pH 2, 10 and 12 correlated negatively (r = -0.30) with NaCl
      concentration levels; however, the correlation was not significant (p > 0.05).
      The flour dispersions had lower viscosities at acid pH and in the presence of
      NaCl than at neutral and alkaline pH values. Results indicated the flour could be
      used in food product supplementation.

PMID- 11318500
TI  - Effect of heat processing on in vitro protein digestibility and some chemical
      properties of African breadfruit (Treculia africana Decne) seeds.
AB  - The effects of dry heat (roasting) and moist heat (boiling) on in vitro protein
      digestibility, protein fractions and other chemical properties of African
      breadfruit (Treculia africana Decne) seed that affect their utilization as a
      source of human food were investigated. Chemical analyses showed that the crude
      protein and fat contents of the unprocessed (raw) seeds were 20. 1% and 13.7%,
      respectively. The level of phytic acid in the raw seed (1.19 mg/g) was lower than
      the levels found in some commonly consumed pulses in Nigeria. Albumin and
      globulin protein fractions were found to be the major seed proteins of African
      breadfruit seed, constituting 67.8% of the total protein of the raw seed. There
      were no significant (p > 0.05) differences between crude protein, ash and fat
      contents of the raw and heat processed samples. Boiling proved more effective
      than roasting for improving protein digestibility and for reducing the levels of
      trypsin inhibitor, phytic acid and polyphenols of the samples. The complete
      removal of these antinutrients, however, would require a more severe heat
      treatment of the seed, which in turn would profoundly reduce the nutritional
      value and availability of proteins, as demonstrated by the low values obtained
      for in vitro protein digestibility, protein fractions and protein extractability.

PMID- 11318501
TI  - Levels of beta-carotene and effects of processing on selected fruits and
      vegetables of the arid zone of India.
AB  - Some locally available fruits and vegetables of the arid zone of Rajasthan were
      analyzed for their beta-carotene content; the selected fruits and vegetables
      were: Dansra (Rhus myserensis), Kachri (Cucumis collosus), fruit Kachri (Cucumis
      collosus), Kair (Capparis decidua) and Sanghri (Prosopis cineriria). The beta
      carotene contents of the samples were estimated in fresh and various processed
      states (blanched, dried and roasted). The results showed the heat lability of
      beta-carotene. Among the samples, kair was found to be the richest source of beta
      carotene. Variety, too, had an impact on the content of this fat soluble vitamin.

PMID- 11318502
TI  - Effect of exposure to a country liquor (Toddy) during gestation on lipid
      metabolism in rats.
AB  - The objective of this study was to determine the effects of country liquor Toddy
      and its equivalent quantity of ethanol on lipid metabolism during gestation in
      rats. Female rats weighing an average of 125 g were exposed to Toddy (24.5
      ml/body weight/day) and ethanol (0.52 ml/kg body weight/day) for 15 days before
      conception and throughout gestation. On the 19th day of gestation, altered liver
      function and hyperlipidemia was seen in both the treated groups. Altered liver
      function was evidenced by the increased activity of alcohol dehydrogenase,
      aldehyde dehydrogenase, glutamic oxaloacetic transaminase or aspartate amino
      transferase (GOT), glutamic pyruvic transaminase or alanine amino transferase
      (GPT) and gamma glutamyl transpeptidase (GGT). Hyperlipidemia was caused by
      increased biosynthesis and decreased degradation of lipids. The incorporation of
      14C acetate in lipids and activities of HMG CoA reductase and lipogenic enzymes
      were elevated and activity of LPL and bile acids contents were decreased. Toddy
      treated rats were more severely affected than those receiving an equivalent
      quantity of ethanol. Toddy seemed to potentiate the toxicity induced by alcohol
      indicating the role of the nonethanolic portion. Hepatic functions were also
      affected.

PMID- 11318503
TI  - Amino acid composition and biological evaluation of the protein quality of high
      lysine barley genotypes.
AB  - The protein quality of high lysine barley genotypes Notch1 Notch2, Riso-1508 and
      Hiproly grown in Indian soil was evaluated by determining amino acid composition
      and also by rat growth and nitrogen balance studies. Protein and fat contents
      were found to be highest in Riso-1508. Lysine concentration (5.26 g/16g N) of
      Riso-1508 was also highest compared to the other high lysine genotypes. Rat
      feeding trials indicated that the growth promoting qualities of the proteins of
      genotype Riso-1508 were significantly (p < 0.05) higher than the low lysine
      barley genotype. The comparatively low lysine barley diet had more digestible
      protein than the high lysine barley diet. However, the BV and NPU of the high
      lysine barley were significantly (p < 0.05) higher. This improvement is of
      importance in meeting the essential amino acid requirements of man as well as
      other monogastric animals. The study showed that the high lysine barley harvested
      in Indian agroclimatic conditions retained high lysine quality.

PMID- 11318504
TI  - Comparison of palm and mixtures of refined palm and soybean oils on serum lipids
      and fecal fat and fatty acid excretions of adult humans.
AB  - The effects of palm (P) and mixtures of palm and soybean (PS), palmolein and
      soybean (POS), palmstearin and soybean (PSS) oils on serum lipids and fecal fat
      and fatty acid excretions of humans were studied. Each oil was the dominant fat
      in diets consumed by ten normolipidemic live-in individuals. Test diets were
      assigned by randomization. All four diets had a similar influence on total
      cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL),
      very low density lipoprotein (VLDL), triglycerides (TG) and phospholipids (PL).
      Fecal fat excretion was higher (1.81, 1.80 g/d) with PS and PSS and lower (1.78,
      1.42 g/d) with P and POS diets. Excretions of palmitic (C16: 0), oleic (C18: 1),
      and linoleic (C 18: 2) acids were similar for all diets. Excretions of stearic
      acid (C 18: 0) were higher when feeding POS and PSS, and lower with feeding P and
      PS; the changes were statistically significant at p <0.05. More linolenic acid
      (C18: 3) was excreted when P was fed compared to the feeding of PS, POS, and PSS.
      Changes in linolenic acid excretion between P and POS were statistically
      significant at p <0.05. It was concluded that there were no significant
      differences in serum lipid concentrations due to feeding palm or any of the
      refined palm and soybean oil mixtures. However, a significant difference was
      found in C18: 0 excretions with feeding POS and PSS compared to when P and PS
      were fed. Similarly, significant C18: 3 excretion was found with feeding P
      compared to when POS was fed.

PMID- 11318505
TI  - Cassava-soy weaning food: biological evaluation and effects on rat organs.
AB  - Weaning food was formulated using a cassava product, 'Tapioca' (TAP),
      supplemented with roasted-sprouted soybeans (SS), with and without additional
      (10%) malted sorghum flour (MS). Biological evaluation was carried out on the
      formulations using 4-5 week old weanling albino rats, with Cerelac (a commercial
      maize-milk weaning food) as the control diet. There were increases in growth rate
      of rats fed with both the test and control diets. There were no significant (p
      >0.05) differences between the test diets and control diet in true digestibility
      values. The biological value (BV) and net protein utilization (NPU) values for
      the formulated diets were above the recommended minimum values. The weight of
      organs (small intestine, pancreas, liver and heart) of rats fed TAP + SS and TAP
      + SS + MS based diets were not higher than those of organs of rats fed Cerelac.
      It was concluded that cassava products could potentially be employed successfully
      in the preparation of weaning foods of comparable quality to available commercial
      brands.

PMID- 11318506
TI  - Effect of fermentation on sorghum protein fractions and in vitro protein
      digestibility.
AB  - Changes in pH, titratable acidity, total soluble solids and proteins of Dabar
      sorghum (Sorghum bicolor (Linn) Moench.) during natural fermentation at 37
      degreesC for up to 36 h were monitored. The pH of the fermenting material
      decreased sharply with a concomitant increase in the titratable acidity. Total
      soluble solids increased with progressive fermentation time. The crude protein
      and non-protein nitrogen slightly increased during the last stages of
      fermentation. The in vitro protein digestibility markedly increased as a result
      of fermentation. The globulin plus albumin fractions increased significantly (p <
      or = 0.05) during the first 8 h of fermentation. Kaffirin fraction decreased
      during the first 8 h of fermentation but increased sharply as fermentation
      progressed. Cross-linked kaffirins fluctuated during the fermentation process.
      Glutelin like protein, which was the minor fraction, true glutelins, the second
      most abundant fraction, together with non-extractable proteins fluctuated during
      the fermentation process.

PMID- 11318507
TI  - Development of an owoh-type product from African yam beans (Sphenostylis
      stenocarpa) (Hoechst (ex. A. Rich.) Harms.) seeds by solid substrate
      fermentation.
AB  - African yam beans were fermented to obtain an owoh-type product. Microorganisms
      associated with the fermentation were Bacillus licheniformis, B. pumilus, B.
      subtilis and Staphylococcus sp. Total microbial counts increased from 1.53 x
      10(5) cfu/g to 1.51 x 10(9) cfu/g under aerobic conditions, and from 8.0 x 10(3)
      cfu/g to 1.35 x 10(7) cfu/g under conditions of reduced oxygen tension. The pH of
      the substrate increased throughout the fermentation, from 6.8 to 7.5. A
      comparison of unfermented seeds with the fermented product showed that there were
      decreases in the levels of total nitrogen, crude protein, crude fiber and lipids,
      and that there were increases in the levels of carbohydrate and total organic
      matter. Enzyme activities during fermentation revealed that amylase production
      was erratic showing a slight increase during the first 24 h followed by a steep
      rise in activity in the next 24 h. By contrast, lipase activity increased rapidly
      throughout the first 72 h while proteinase activity followed a type of sigmoid
      curve with a steady increase in activity within the first 48 h and a relatively
      high activity until the 96th h before plunging downwards.

PMID- 11318508
TI  - Effect of sesame seed flour on millet biscuit characteristics.
AB  - Defatted sesame seed flour replaced millet flour at 30, 40, and 50% and was used
      to prepare biscuits. Protein content of the biscuits was significantly (p < or =
      0.05) increased by replacement with sesame seed flour. Millet flour biscuits were
      heavier than those from the blends. Diameters and weights of biscuits were
      reduced and thicknesses and spread factors were increased with increasing level
      of sesame replacement. Sensory evaluation results showed that the biscuits were
      highly rated for flavor and crispiness but considered poor in color.

PMID- 11318509
TI  - Chronic renal failure and anterior hypophysial hormones.
AB  - Kidneys are not only organs with an excretory function but they produce their own
      endocrine factors which are involved in supporting homeostasis in the organism.
      The kidneys are the organs in which metabolism and biodegradation of many
      hormones take place. Together with the liver, the kidneys actively take part in
      the catabolism of hormones.

PMID- 11318510
TI  - Control of brittleness in butyl-methylmethacrylate resin embedding mixtures to
      facilitate their use in immunofluorescence microscopy.
AB  - Butyl-methylmethacrylate resin mixtures were tested for brittleness-inducing
      factors in polymerised resin using a rapid quantitative scoring technique. The
      major source of brittleness was identified as the reducing agent dithiothreitol,
      which is commonly included in resin mixtures at 10 mM, to protect against tissue
      oxidation. Lowering the dithiothreitol content to 5 mM substantially reduced
      brittleness. Changing the 4:1 ratio of butyl- to methylmethacrylate to 9:1 or
      3:2, and reducing the concentration of the catalyst, benzoin ethyl ether, to
      0.25% also reduced dithiothreitol-induced brittleness. Polymerisation at
      temperatures close to 0 degrees C increased dithiothreitol-induced brittleness,
      but this was controlled in the 4:1 and 9:1 resin mixtures by lowering the
      catalyst concentration from 0.5 to 0.25%. Degassing the resin mixture with
      nitrogen gas prior to polymerisation did not reduce brittleness. Immunolabelled
      onion roots which were embedded using the 3:2 resin mixture ratio, 5 mM
      dithiothreitol and the 0.25% catalyst concentration, showed excellent
      preservation of cortical microtubule arrays.

PMID- 11318511
TI  - Karyotype analysis in Brachiaria (Poaceae) species.
AB  - This is the first karyotype characterization of Brachiaria species. Twelve
      accessions belonging to five species were analysed. The basic chromosome number
      was x = 9 and 7, the same reported for the tribe Paniceae. Variations in the
      chromosome number were observed in B. decumbens (2n = 18; 36) and B. humidicola
      (2n = 36; 42; 54). Chromosome numbers of 2n = 18 in B. ruziziensis and 2n = 36 in
      B. brizantha and B. jubata were recorded. Inter- and intraspecific karyotype
      differentiation of the accessions analysed was facilitated by variations in
      karyotypic symmetry. The karyotypes were generally considered symmetrical, with a
      tendency to asymmetry in the direction of the polyploids. It is suggested that
      addition, deletions and mainly polyploidy have been the most direct causes
      involved in the chromosome evolution of this genus.

PMID- 11318512
TI  - Cytogenetic damage in plastic industry workers exposed to polyvinyl chloride.
AB  - Cytogenetic investigations on peripheral blood lymphocytes of 40 workers exposed
      to polyvinyl chloride in the plastic industry were undertaken. These were
      compared with an equal number of occupationally unexposed and matched controls in
      relation to age, sex and smoking habits. The mitotic index (MI), chromosomal
      aberrations (CA), sister chromatid exchanges (SCE) and satellite associations
      (SA) were analysed. All the parameters showed a significant increase (p <0.01) in
      the exposed sample compared with the controls, viz MI, 3.64-6.30, CA 1.02-3.77,
      SCE 3.40-7.83 and SA 5.57-12.05. The occurrence of the DG type of satellite
      association B was highest and that of 3D type lowest. The frequencies of all the
      parameters increased with the duration of exposure, but MI declined after 15
      years of exposure.

PMID- 11318513
TI  - Genetic inactivation of Leuciscus idus L. (ide) oocytes using UV irradiation.
AB  - Oocytes of Leuciscus idus were genetically inactivated using ultraviolet (UV)
      irradiation. Eggs for the experiment were obtained from dark-coloured females,
      whereas milt was taken from yellow-coloured (recessive marker) males. The
      survival at the eleutheroembryo stage (free embryo) in all experimental groups
      fertilized with genetically inactivated spermatozoa was much lower than in
      control groups. All haploid embryos showed morphological abnormalities, such as a
      stunted body and a poorly formed retina, and the condition was referred to as the
      haploid syndrome. The androgenetic origin (haploid or diploid embryos) was
      checked using a recessive colour marker ('blond'). The optimal doses of UV
      irradiation were 3,456-4,608 Jm(-2) at which almost 100% haploid embryos were
      produced at a hatching rate of >15%. Lower UV-ray doses influenced abnormal
      embryo development. Ploidy level recognition showed a typical value of mean
      active nucleoli per cell in haploid and diploid (control fish and spontaneous
      androgenotes) specimens. Abnormal dark embryos were classified as aneuploids.

PMID- 11318514
TI  - A simple method for measuring of intestinal solute transport in mucosal biopsy
      specimens.
AB  - Accurate in vitro measurements of intestinal mucosal solute uptake in humans are
      often difficult because only small amounts of tissue material are available. We
      describe a miniaturized everted sleeve method of measuring intestinal solute
      uptake in endoscopy biopsy samples that combines simplicity, good tissue
      viability and reproducibility. Biopsies were mounted on a dressmaker needle head
      stationed immediately over a stirring bar rotating at 1200 rpm. This approach was
      used to measure taurocholate uptake in sheep and human endoscopy biopsies.
      Comparison was made to conventional standardized everted sleeve preparations. Na+
      dependent uptake rates correlated well among individual sheep (R2 = 0.88, P <
      0.05). There was excellent correlation between conventional and biopsy
      preparations in humans (R2 = 0.98; P < 0.05). The biopsy method overestimated
      diffusional uptake rates in sheep and humans by two to three fold when compared
      to conventional everted sleeve preparations. We conclude that this method is
      valuable to measure Na+-dependent solute uptake rates in biopsy samples from
      human intestine.

PMID- 11318515
TI  - High prevalence of TT virus in human bile juice samples: importance of secretion
      through bile into feces.
AB  - TT virus (TTV) is much more prevalent than we once imagined. With the use of
      primers designed from the noncoding regions, a more than 90% rate of TTV
      infection in the general population by polymerase chain reaction (PCR) has been
      reported, showing that nonparenteral transmission must play an important role to
      its epidemiology. We considered that TTV may be secreted through bile juice into
      feces to establish nonparenteral infection. Paired bile juice and serum samples
      were obtained from 26 patients who were receiving bile drainage. Feces were also
      recovered after the drainage tube was removed. TTV DNA was detected from 22
      patients in serum (84.6%), and they were all TTV DNA positive in bile juice. Most
      feces samples recovered from TTV-positive patients were also TTV DNA positive.
      Secretion of TTV into bile juice appears to be common, and this could play an
      important role to its transmission and its epidemiology.

PMID- 11318516
TI  - Complete treatment of ruptured hepatic cyst into biliary tree by ERCP.

PMID- 11318517
TI  - Kidney transplantation in patients with chronic hepatitis B virus infection: is
      the prognosis worse?
AB  - The impact of hepatitis B virus (HBV) infection on the long-term outcome of
      kidney transplant patients is controversial. A total of 34 chronic hepatitis B
      surface antigen (HBsAg) carriers among 143 renal allograft recipients were
      identified in this study (mean follow-up period: 5.6+/-3.3 years; range: 1-13
      years). During the follow-up, one HBsAg-positive recipient with preexisting
      cirrhosis died of liver failure, and seven (21%) others developed serious HBV
      related complications (four fulminant hepatitis, two hepatocellular carcinoma,
      one cirrhosis), and four died. Although HBsAg-positive recipients had a higher
      rate of liver-related complications and deaths than HBsAg-negative recipients
      did, there were no significant differences in the long-term graft and patient
      survival between the two groups. The survival rates, liver-related complications,
      and deaths in HBsAg-positive allograft recipients and 28 HBsAg-positive uremic
      patients under dialysis were similar. In conclusion, HBV infection is not a
      contraindication to kidney transplantation. However, pretransplant candidates
      should be warned of potentially serious liver-related complications.

PMID- 11318518
TI  - Effects of extrinsic denervation with or without ischemia-reperfusion injury on
      constitutional mucosal characteristics in porcine jejunoileum.
AB  - We investigated the effects of jejunoileal denervation with or without ischemia
      reperfusion on mucosal characteristics and small intestinal structure. Growing
      pigs underwent sham laparotomy, jejunal transection, or extrinsic jejunoileal
      denervation with or without in situ ischemia-reperfusion. Small intestinal
      morphology, crypt cell proliferation, enterocyte ultrastructure, and
      disaccharidase activities were analyzed from jejunum and ileum after eight weeks.
      Immunohistological analysis of the ileum showed no staining of catecholaminergic
      neurons after extrinsic denervation. Neural isolation of the jejunoileum with or
      without ischemia-reperfusion injury reduced weight gain and villous enterocyte
      density in the ileum, abolished the proximodistal gradient of sucrase activity,
      and increased mucosal thickness, villus height, and villus surface area in the
      ileum. However, gross jejunoileal morphology, crypt cell proliferation, and
      enterocyte ultrastructure remained unchanged. In conclusion, jejunoileal
      denervation in growing pigs selectively modulates constitutional mucosal
      characteristics in the ileum, presumably due to altered enterocyte turnover,
      without a decrease in small intestinal absorptive surface area. These changes are
      independent of short ischemia and subsequent reperfusion.

PMID- 11318519
TI  - Aspirin-related hepatotoxicity in a child after liver transplant.

PMID- 11318520
TI  - Time-dependent modifications of splanchnic circulation in female pigs submitted
      to end-to-side portacaval anastomosis.
AB  - Fractional systemic bioavailability of orally administered drugs was found to be
      unexpectedly low in liver cirrhosis, even after surgical portal-systemic
      shunting. Fecal loss or intestinal first-pass elimination were assumed to explain
      the finding. In this paper we evaluated alternative pathophysiological
      interpretations relating low bioavailability to adaptive circulatory
      modifications. D-Sorbitol was used because its hepatic extraction is very high
      and hepatic removal follows a flow-dependent clearance regimen. D-Sorbitol
      bioavailability was measured at steady state in pigs submitted to end-to-side
      portacaval anastomosis, immediately after surgery and four weeks later.
      Intestinal first-pass elimination dependent on fecal loss and intraluminal
      degradation was excluded by administering D-sorbitol into the superior mesenteric
      artery. Almost complete bioavailability was observed immediately after surgery (N
      = 6, 0.96+/-0.08); four weeks later the bioavailability dropped (-36.8+/-18.7%; P
      < 0.001) while hepatic clearance significantly increased (+83.6+/-47.9%; P <
      0.01). Experimental data support the hypothesis that adaptive circulatory changes
      spontaneously occur after some time, leading to a lower than expected portal
      bioavailability.

PMID- 11318521
TI  - Autonomic dysfunction and cholelithiasis in patients with cirrhosis.
AB  - Gallstones are seen in 33-46% of patients with cirrhosis, and their prevalence is
      known to increase with the duration and severity of liver disease. We
      hypothesized that autonomic neuropathy may contribute to the formation of
      gallstones or gallbladder disease, as in diabetics with autonomic neuropathy, due
      to impaired gallbladder emptying. The objective of our study was to determine the
      prevalence of gallstones or gallbladder disease in cirrhotic patients with and
      without autonomic neuropathy. We determined autonomic function tests, gallstones,
      and other gallbladder disease in 123 (male 71) with varying severity of liver
      disease (Child classes: A, 40; B, 45; C, 35). In all, 54 patients had gallstones
      and an additional 22 patients had other gallbladder disease (cholecystitis,
      common bile duct stones, or debris). Autonomic neuropathy was seen in 97 patients
      (one abnormal test in 48 and two or more in 49). The prevalence of gallstones was
      similar in Child A (57%), Child B (64%), and Child C (63%) cirrhosis. The
      gallstones or gallbladder disease was not increased in women, blacks, diabetics,
      or alcoholic cirrhotics. The prevalence of gallbladder disease was increased in
      patients with autonomic neuropathy (51% vs 35%, P = 0.08); in patients with Child
      C cirrhosis, gallstones (P = 0.018) and gallbladder disease (P = 0.03) were seen
      more commonly in patients with autonomic neuropathy. Our findings suggest that
      autonomic neuropathy may contribute to the formation of gallstones in patients
      with advanced cirrhosis, perhaps by impairing gallbladder and sphincter of Oddi
      dysmotility.

PMID- 11318522
TI  - Therapy of refractory ascites with ultrafiltration and peritoneal reinfusion in a
      patient with right ventricular dilated cardiomyopathy.

PMID- 11318523
TI  - Portal hemodynamics in fulminant hepatic failure as assessed by duplex Doppler
      ultrasonography.
AB  - Portal hypertension usually occurs in patients with fulminant hepatic failure
      (FHF). There is, however, no information on portal venous hemodynamics in
      patients with FHF. Therefore, we studied the portal venous hemodynamics in
      patients with FHF using duplex Doppler ultrasonography. We measured the portal
      vein diameter, flow velocity, and volume flow with duplex Doppler ultrasonography
      in 29 patients with FHF and 15 patients with uncomplicated acute viral hepatitis.
      No significant difference was observed in the portal vein parameters in the two
      groups. Nineteen patients with FHF survived. No difference in portal flow
      velocity and flow rate was observed between survivors and nonsurvivors. A
      significantly lower portal flow velocity was observed in nine patients of FHF
      with ascites compared with those without ascites (12.29+/-2.81 vs 16.26+/-4.87
      cm/sec; P < 0.01). Portal hemodynamics do not significantly change in fulminant
      hepatic failure; therefore, it has no prognostic significance.

PMID- 11318524
TI  - A long-term follow-up analysis of serial core promoter and precore sequences in
      Japanese patients chronically infected by hepatitis B virus.
AB  - To investigate the association of hepatitis B virus (HBV) with core promoter
      mutation (T1762A1764) or precore mutation (A1896) with the clinical course of
      illness, we analyzed serial core promoter and precore sequences in 22 patients
      with HBV-associated chronic liver disease who were followed for 12+/-4 years
      (mean +/- SD). Sixteen of 22 patients were positive for HBeAg at baseline, and 15
      of the 16 patients seroconverted to anti-HBe during the observation period.
      T1762A1764 mutation was detected in 16 of 22 patients, including 11 patients
      positive for HBeAg, at baseline. During the follow-up period, A1896 mutation
      emerged in 7 of 16 patients who had the wild-type HBV or only the T1762A1764
      mutation at baseline. Sustained remission of hepatitis correlated with the low
      level of viremia, but did not with type of mutations. These results indicate that
      HBV with T1762A1764 mutation tends to precede A1896 mutation during the course of
      infection in Japanese patients with chronic liver disease.

PMID- 11318525
TI  - Rapid decrease of plasma HCV RNA in early phase of twice daily administration of
      3 MU doses interferon-beta in patients with genotype 1b hepatitis C infection: a
      multicenter randomized study.
AB  - Virological response to interferon (IFN) is poor in patients with plasma levels
      of HCV RNA higher than 1 Meq/ml and genotype 1b hepatitis C viral infection. In
      60 patients, a randomized control study was conducted to compare 3 MU of IFN-beta
      twice daily for four weeks (group A) and 6 MU once a day for four weeks (group B)
      followed by a four-week administration of 6 MU once a day. The plasma levels of
      HCV RNA, determined by an amplicore-monitor method, for patients in group A were
      significantly lower than those for group B at the fourth and eighth day of IFN
      administration, and complete virological responses were noted in two patients
      from group A but none in group B. It is concluded that twice daily administration
      of 3 MU IFN-beta is more effective than once a day 6 MU in the early phase of IFN
      therapy.

PMID- 11318526
TI  - Increased levels of gammaGT suggest the presence of bile duct lesions in patients
      with chronic hepatitis C: absence of influence of HCV genotype, HCV-RNA serum
      levels, and HGV infection on this histological damage.
AB  - Damage to bile ducts in chronic hepatitis C is a characteristic histological
      lesion. Moreover, the presence of abnormal levels of gammaGT in these patients is
      also a common finding. Assessing whether the presence of bile duct lesions is
      indicated by biochemical abnormalities or whether virological characteristics can
      influence their development may help in the definition of clinical-histological
      relationships in chronic hepatitis C. In this study we evaluated the
      relationships among routine biochemical parameters, serum bile acids, and pi
      class glutathione S-transferase levels, and the presence of bile duct lesions in
      60 patients with chronic hepatitis C. Furthermore, we assessed whether the
      presence of bile duct lesion might be related to HCV genotype, HCV-RNA serum
      levels, and positivity for HGV-RNA. We found that gammaGT was the only parameter
      related to the presence of bile duct lesions. Although a trend towards higher
      serum bile acids and pi-class glutathione S-transferase levels was observed in
      patients with bile duct lesions, this trend did not reach statistical
      significance. Different HCV genotypes and RNA levels, and HGV-RNA positivity did
      not seem to influence the presence of bile duct damage. In conclusion we found
      that gammaGT levels point out the presence of bile duct lesions in patients with
      chronic hepatitis C. Since we observed a different pattern of alteration of
      gammaGT, serum bile acids, and pi-class glutathione S-transferase, we suggest
      that these various biochemical alterations reflect a more complex damage to bile
      duct structures, which is not likely represented by the common assessment of bile
      duct lesions. Viral factors such as HCV genotype and RNA levels as well as HGV
      RNA positivity are probably not the main cause of this histological damage.

PMID- 11318527
TI  - Collapsing focal segmental glomerulosclerosis with recovery of renal function: an
      uncommon complication of interferon therapy for hepatitis C.

PMID- 11318528
TI  - Pathological pancreatic exocrine function and duct morphology in patients with
      cholelithiasis.
AB  - Most authors claim alcohol consumption to be the only relevant reason for chronic
      pancreatitis. However, gallstones might cause this disease, as they do cause
      acute pancreatitis. In this study 91 gallstone patients and 94 age-matched
      controls were investigated concerning exocrine pancreatic function (fecal
      elastase-1 concentrations). Furthermore x-rays of 100 consecutive ERCP patients
      were evaluated for differences concerning pancreatic duct changes between
      patients with and without evidence of cholelithiasis. Pathological elastase 1
      levels were more frequent in gallstone patients (30,8%) as compared to age
      matched controls (19%). Symptoms such as upper abdominal pain, bloating, and fat
      intolerance were reported more often in gallstone patients. In ERCP of gallstone
      patients (N = 60), 77% were found to have chronic pancreatitis according to the
      Cambridge classification, while in nongallstone-patients (N = 32) 47% had chronic
      pancreatitis. In conclusion, according to these data a pathophysiological
      connection between gallstones and chronic pancreatitis appears to be probable.

PMID- 11318529
TI  - Role of fibrates and HMG-CoA reductase inhibitors in gallstone formation:
      epidemiological study in an unselected population.
AB  - Fibrate derivatives and HMG-CoA reductase inhibitors modify homeostasis of
      cholesterol. The aim of this study was to assess in an unselected population
      whether these hypolipidemic drugs are risk factors for cholelithiasis or,
      conversely, are protective agents. Both sexes, all socioeconomic categories,
      pregnant women, and cholecystectomized subjects were included. Clinical data
      collection and gallbladder ultrasonography were both carried out in a double
      blind fashion. Fibrate derivatives were predominantly fenofibrate, HMG-CoA
      reductase inhibitors were simvastatin and pravastatin. On univariate analysis,
      age (>50 years), sex, and use of fibrates were found to be significantly related
      to the presence of cholelithiasis. Age, sex, and fibrate treatment remained
      independently correlated with the presence of gallstones on multivariate
      analysis. With fibrates, the relative risk for lithiasis was 1.7 (P = 0.04). The
      HMG-CoA reductase inhibitors were not associated with a protective effect on
      univariate analysis. Of the lipid-lowering drugs, only fibrate derivatives were
      found to increase the risk of gallstone formation.

PMID- 11318530
TI  - Apoptosis induced by ischemia-reperfusion and fasting in gastric mucosa compared
      to small intestinal mucosa in rats.
AB  - The effect of ischemia-reperfusion and 48-hr fasting on apoptosis was
      characterized in rat gastric mucosa and compared to small intestinal mucosa.
      Under halothane anesthesia, the celiac artery or superior mesenteric artery in
      the rat was occluded for 60 min followed by reperfusion. Occlusion of the celiac
      artery reduced blood flow in the stomach and occlusion of the mesenteric artery
      reduced blood flow in the small intestine. Additional rats were fasted for 48 hr
      to evaluate the effect of fasting on mucosal apoptosis. The ratios of fragmented
      DNA to total DNA, electrophoresis, and immunohistochemical staining were examined
      after ischemia-reperfusion or fasting. Apoptosis was not induced significantly in
      the gastric mucosa after ischemia-reperfusion, although it increased dramatically
      in the intestinal mucosa after ischemia-reperfusion. Further, after 48 fasting,
      apoptosis was induced in the small intestine, but not in the stomach. These
      results indicate that rat gastric mucosa is not as sensitive as small intestinal
      mucosa to ischemia-reperfusion or fasting-induced apoptosis.

PMID- 11318531
TI  - Gastric epithelial cell proliferation in patients with liver cirrhosis.
AB  - An increased risk for gastric cancer in patients with liver cirrhosis has
      recently been reported. This study was performed in order to determine gastric
      epithelial cell proliferation in cirrhotic patients and to evaluate the role of
      congestive gastropathy (CG) and Helicobacter pylori infection in this process.
      Thirty-six cirrhotic patients and 18 controls were enrolled in the study. All
      patients underwent endoscopy and three biopsies were performed in the antrum and
      three in the gastric body. The presence of H. pylori infection was assessed by a
      rapid urease test and histology. The antral biopsies were used for gastric cell
      proliferation assessment by an immunohistochemical analysis (Ki-67). There was no
      significant difference in epithelial cell proliferation between cirrhotics and
      controls. Gastric proliferation values were higher in patients with H. pylori
      infection compared with uninfected patients, both in cirrhotic (P = 0.003) and in
      control groups (P = 0.06). Among the cirrhotic group, we found a progressive
      increase in gastric cell proliferation values related to the degree of CG, the
      highest values being observed in cirrhotic patients with severe CG. Moreover,
      cirrhotics with both severe CG and H. pylori infection had the highest
      proliferation values when compared with all other subgroups. In conclusion, this
      study found that: (1) CG significantly affects epithelial cell proliferation in
      gastric mucosa in cirrhotic patients, (2) H. pylori infection plays a similar
      role in gastric cell proliferation in both cirrhotic and non-cirrhotic patients,
      and (3) CG and H. pylori could act synergistically in this process.

PMID- 11318532
TI  - Hemoperitoneum as a first manifestation of hepatocellular carcinoma in western
      patients with liver cirrhosis: effectiveness of emergency treatment with
      transcatheter arterial embolization.
AB  - Hemoperitoneum is a well-known form of hepatocellular carcinoma presentation and
      represents a frequent complication in countries with a high incidence of
      hepatocellular carcinoma, but it is rarely seen in Western countries. Our aim was
      to report the results and describe the arteriographic and CT-scan characteristics
      in a series of seven consecutive patients. They were admitted to our hospital
      because of hemoperitoneum due to ruptured tumor as a first manifestation of
      hepatocellular carcinoma, and the rupture was effectively controlled by
      transcatheter arterial embolization. From April 1989 to April 1998, 440
      consecutive patients were admitted to our liver unit with the diagnosis of
      hepatocellular carcinoma and liver cirrhosis. Fourteen patients (3%) presented
      with acute hemoperitoneum due to tumor rupture as a first manifestation of
      hepatocellular carcinoma. We here report our experience in the group of patients
      treated by transcatheter arterial embolization. Mean age was 67.1+/-5 years
      (range, 61-73). All patients presented with sudden abdominal pain, abdominal
      distension, and four patients had symptoms of acute anemia. In all cases the
      ruptured tumor was subcapsular. The procedure was effective in the control of
      bleeding in all cases, without significant impairment in liver function or
      treatment-related deaths. In six of the seven patients, a self-limited
      postembolization syndrome was observed. Mean survival time was 273+/-488.7 days
      (range: 15-1290). Three patients survived more than six months but at the time of
      evaluation, only one patient was alive. In conclusion, the present results
      confirm that transcatheter arterial embolization is an effective and well
      tolerated treatment in the management of hemoperitoneum due to ruptured
      hepatocellular carcinoma in patients with liver cirrhosis.

PMID- 11318533
TI  - Expression of c-myc promoter binding protein (MBP-1), a novel eukaryotic
      repressor gene, in cirrhosis and human hepatocellular carcinoma.
AB  - We have examined the expression of c-myc and c-myc promoter binding protein (MBP
      1), a novel eukaryotic repressor, in human hepatocellular carcinoma and cirrhosis
      by semiquantitative reverse transcription PCR amplification. Levels were
      normalized for glyceraldehyde-3-phosphate dehydrogenase messenger RNA and then
      compared between these two groups and to normal liver. We found that MBP-1
      expression was significantly decreased in cirrhosis and c-myc and MBP-1 were even
      further diminished in hepatocellular carcinoma. There was no clear correlation
      between MBP-1 and c-myc messenger RNA levels. Our results therefore suggest that
      expression of MBP-1 and c-myc are decreased in a stepwise fashion in the presence
      of chronic liver disease and hepatocellular carcinoma in humans and that further
      study of the interactions of these two genes and their products is warranted to
      determine their role in human hepatocarcinogenesis.

PMID- 11318534
TI  - Primary gastrointestinal follicular center lymphoma resembling multiple
      lymphomatous polyposis.

PMID- 11318535
TI  - Measuring change in quality of life in response to Helicobacter pylori
      eradication in peptic ulcer disease: the QOLRAD.
AB  - This study was designed to determine if a new condition-specific quality of life
      measure, the Quality Of Life in Reflux And Dyspepsia (QOLRAD), was responsive to
      clinical change over a four-week period when evaluating peptic ulcer disease
      patients undergoing Helicobacter pylori (Hp) eradication. A secondary aim was to
      evaluate QOLRAD's psychometric performance. Hp-positive patients with peptic
      ulcer disease were recruited from primary care and gastroenterology clinics (N =
      155). QOLRAD scores improved significantly (P < 0.0001) and mean total score
      increase was 1.07 points on a 7-point scale among 111 subjects who responded to
      Hp eradication. Effect sizes were moderate for responders (0.64) and low for
      nonresponders (0.36). Score changes below 0.60 were associated with the smallest
      improvement in patient and physician condition rating; scores above 1.2 were
      associated with the greatest improvement. The QOLRAD demonstrates reliability and
      validity. Changes in QOLRAD score can be meaningfully related to clinical
      changes, aiding evaluation of health-related quality of life in peptic ulcer
      disease.

PMID- 11318536
TI  - Peptic ulcer occurrence in follow-up of chronic gastritis in patients with
      treated and not eradicated CagA-positive Helicobacter pylori infection.
AB  - The aim of the present prospective investigation was to study 49 dyspeptic
      Helicobacter pylori (HP)-positive (HP+) or -negative (HP), CagA+ and CagA-
      patients with a normal pattern or pure chronic gastritis at initial histology as
      well as normal features or hyperemic gastropathy at initial endoscopy in a two
      year follow up. All the HP+ patients were treated with omeprazole 20 mg twice a
      day plus amoxicillin 1 g twice a day for two weeks. No substantial change was
      seen in gastritis in CagA+ patients in whom the infection was not eradicated,
      and, in contrast, a progressive improvement in 13/14 successfully treated
      patients was found. At endoscopy, a progressive change to a normal picture was
      seen in 8 and no change in 6 of 14 patients whose HP infection was eradicated, in
      contrast a worsening in the 9 HP+ patients who were still infected was observed.
      In particular, peptic lesions arose in 6 of 21 CagA+ patients in whom the
      infection was not eradicated. In conclusions, the lack of change in chronic
      gastritis at histology and the progressive worsening of endoscopic hyperemic
      gastropathy (with peptic lesions arising in 28,6%) when HP+ CagA+ infection is
      not eradicated, unlike the progressive improvement of the anatomoclinical
      condition in the patients whose infection was eradicated, draws attention to the
      relevance of eradicating HP in CagA+ patients even when no peptic lesion is found
      at initial endoscopy.

PMID- 11318537
TI  - Efficacy of rabeprazole once daily for acid-related disorders.
AB  - Proton-pump inhibitors (PPIs) have revolutionized the treatment of
      gastroesophageal reflux disease (GERD) and peptic ulcer. To evaluate the efficacy
      of the new PPI rabeprazole, 12 controlled clinical trials were conducted
      worldwide-three for each indication (erosive or ulcerative GERD healing, long
      term GERD healing maintenance, duodenal ulcer healing, and gastric ulcer
      healing). Rabeprazole was compared to placebo, the H2-receptor antagonist
      ranitidine, and the PPI omeprazole. Treatment duration ranged from < or =4 weeks
      for duodenal ulcer to < or =6 weeks for gastric ulcer, < or =8 weeks for GERD
      healing, and 1 year for maintenance of GERD healing. Rabeprazole was as effective
      as omeprazole for each indication and significantly more effective than
      ranitidine for healing of GERD (87% vs 66%) and duodenal ulcer (83% vs 73%).
      Rabeprazole was also superior to ranitidine in providing symptom relief,
      particularly in GERD.

PMID- 11318538
TI  - Role of esophageal function tests in diagnosis of gastroesophageal reflux
      disease.
AB  - Clinicians typically make the diagnosis of gastroesophageal reflux disease (GERD)
      from the clinical findings and then prescribe acid-suppressing drugs. Endoscopy
      is usually done for persistent or severe symptoms. Esophageal function tests
      (EFTs: esophageal manometry and 24-hr pH monitoring) are generally reserved for
      patients who have the most severe disease, including those being considered for
      surgery. We hypothesized that EFTs are more accurate than symptoms and endoscopy
      in the diagnosis of GERD. This was a retrospective study undertaken in a
      university tertiary care center. Between October 1989 and November 1998, 822
      patients with a clinical diagnosis of GERD (based on symptoms and endoscopic
      findings) were referred for EFTs. The patients were divided into two groups
      depending on whether the 24-hr pH monitoring score showed GERD (group A, GERD-;
      group B, GERD+). The groups were compared with respect to the incidence and
      severity of symptoms, presence of a hiatal hernia on barium x-rays, presence and
      severity of esophagitis on endoscopy, and esophageal motility. In all, 247
      patients (30%) had normal reflux scores (group A, GERD-), and 575 patients (70%)
      had abnormal scores (Group B, GERD+). Eighty percent of group A and 88% of group
      B had been treated with acid-suppressing medications. The incidence of heartburn
      and regurgitation was similar in the two groups. Grade I-II esophagitis was
      diagnosed by endoscopy in 25% of group A and 35% of group B, and grade III
      esophagitis in 4% of group A and 11% of group B. Esophageal manometry showed that
      group B more often had esophageal dysmotility, consisting of a hypotensive lower
      esophageal sphincter and abnormal esophageal peristalsis. These data show that:
      (1) symptoms were unreliable for diagnosing GERD; (2) endoscopic evidence of
      grade I-II esophagitis was diagnostically nonspecific, and grade III was much
      less certain than claimed in other reports; and (3) pH monitoring identified
      patients with GERD and stratified them according to the severity of the disease.
      We conclude that esophageal manometry and pH monitoring are important in
      diagnosing GERD accurately. More liberal use of these tests early in patient
      management would avoid much improper and costly medical therapy and would help
      single out for special attention the patients with GERD who have the most severe
      disease.

PMID- 11318539
TI  - Standard acid reflux testing revisited.
AB  - Patients who present with uncontrolled esophageal acid reflux symptoms require
      endoscopy to determine the presence or absence of ulcers and stenoses, acid
      reflux testing to determine if acid reflux is present, and manometry to evaluate
      esophageal peristalsis and spastic states. These studies are usually done in
      stages, at separate times. Esophageal manometry catheters currently in use have
      an incorporated infusion channel. This allows instillation of a dilute acid meal
      after esophageal manometry has been completed. Standard acid reflux testing can
      then be done using dynamic positioning and physiologic maneuvers. When combined
      with an esophagogastroduodenas copy (EGD), these three studies provide all
      information necessary within 2-3 h to determine further treatment of these
      patients. A total of 210 patients underwent these studies. A hiatus hernia was
      present in 84%. An ineffective lower esophageal sphincter was found in 64%.
      Esophageal hypocontractility was present in 18%, hypercontractility in 14%, and
      dysmotility in 36%. Upper esophageal sphincter was weak in 42%, hypercontractile
      in 42%, and dysmotile in 32%. Acid reflux disease was found in the hiatus hernia
      in 14% and acid reflux to the level of the lower esophagus in 16%, middle
      esophagus in 13%, and upper esophagus in 40%. Distal esophagitis was present in
      47%, esophageal ulceration in 29%, gastric prolapse in 11%, gastritis in 52%,
      bile reflux disease in 10%, and Barrett's epithelium in 5%. In conclusion, an
      extremely high number of patients with esophageal acid reflux disease show
      dysmotility patterns. Standard acid reflux testing using dynamic positioning will
      identify most patients with significant acid reflux disease. When combined with
      an EGD, complete testing for acid reflux disease can be performed at one setting.
      Further study is needed comparing dynamic acid reflux testing to 24-h pH testing.

PMID- 11318540
TI  - Salivary growth factors and cytokines are not deficient in patients with
      gastroesophageal reflux disease or Barrett's esophagus.
AB  - Growth factors, such as epidermal growth factor (EGF), are known to protect upper
      gut mucosa against irritants and to enhance healing of ulcerative lesions in
      animal models. A number of salivary growth factors are found in human saliva. The
      aim of this study was to determine if salivary growth factors and cytokines are
      deficient in patients with esophagitis or with Barrett's metaplasia. Fifteen
      healthy subjects, eight patients with esophagitis, and 13 patients with Barrett's
      metaplasia were included. Salivary concentration of EGF, FGF, IL-1, and IL-6 were
      measured during esophageal saline and hydrochloric acid perfusion and in the
      postprandial state. There was no statistically significant difference in the
      concentration of EGF or cytokines among the three study groups in each
      experimental condition or among the three experimental conditions in each group.
      FGF basic could not be detected in saliva. In conclusion, these findings do not
      support the hypothesis that a deficiency in salivary growth factors or cytokines
      plays a significant role in the development of mild to moderate reflux
      esophagitis or Barrett's metaplasia.

PMID- 11318542
TI  - Gastric accommodation studied by ultrasonography in patients with reflux
      esophagitis.
AB  - The aim of this study was to investigate gastric accommodation to a meal in
      patients with reflux esophagitis using ultrasonography. Twenty consecutive
      patients with reflux esophagitis of grade I (14) or II (6) and 20 healthy
      subjects underwent ultrasonographic measurements of the stomach before and after
      ingestion of a 500 ml soup meal. Reflux esophagitis patients revealed a
      significantly larger sagittal area of the proximal stomach at 5 min (P = 0.002)
      and 15 min (P = 0.007) postprandially and experienced more epigastric fullness
      after the meal (P = 0.0006). Postprandial fullness and sagittal area of the
      proximal stomach correlated significantly (r = 0.69; P = 0.0007). We conclude
      that patients with mild or moderate reflux esophagitis have a larger sagittal
      area of the proximal stomach and more postprandial fullness in response to a soup
      meal than healthy subjects. Postprandial distension of the proximal stomach may
      be a pathogenetic factor in reflux esophagitis.

PMID- 11318541
TI  - Retained gastric antrum syndrome: a forgotten, treatable cause of refractory
      peptic ulcer disease.

PMID- 11318543
TI  - Clonidine inhibits postprandial response of antral myoelectrical activity.
AB  - Clonidine, an alpha2-adrenergic agonist, is known to inhibit gastric motility and
      delay gastric emptying in both humans and animals, but its effect on gastric
      myoelectric activity is unclear. The aim of this study was to investigate the
      effect of clonidine on postprandial gastric myoelectric activity. The experiment
      was performed in eight hound dogs (14.5-22.6 kg) implanted with three pairs of
      bipolar serosal electrodes with an interval of 4 cm and the most distal pair 2 cm
      above the pylorus. Each dog was studied twice on two separate days after a
      complete recovery from surgery. Gastric myoelectrical activity was recorded for
      30 min in the fasting state and 90 min after a solid test meal of 838 kcal. Two
      tablets of clonidine (0.4 mg) were given with the meal in one of the sessions.
      The dominant frequency and power of the slow waves from the most distal pair were
      calculated by computerized spectral analysis. All data were expressed as mean +/-
      SE. A significant postprandial increase in the dominant power of the slow wave
      and an increase in the percentages of gastric slow waves with spike bursts were
      observed in the control session, whereas the dominant frequency of gastric slow
      waves showed a significant postprandial decrease after the meal. The dominant
      power increased 8.24+/-0.5, 8.6+/-0.2, and 7.5+/-0.3 dB, respectively, in the
      first, and second, and third 30-min period after the meal (all P < 0.01 vs
      baseline). Clonidine completely abolished the postprandial increase in the
      dominant power of the gastric slow wave and significantly inhibited spike bursts.
      The dominant power only increased 2.4+/-1.1 dB (P > 0.05 vs baseline; P < 0.01 vs
      the first postprandial period in the control session), 0.6+/-1.5 dB (P > 0.05 vs
      baseline; P < 0.05 vs the second postprandial period in the control session) and 
      1.5+/-2.2 dB (P > 0.05 vs baseline; P < 0.05 vs the third postprandial period in
      the control session) respectively during the first, second, and third periods
      after the meal and clonidine. However, it did not affect the postprandial change
      of the dominant frequency of gastric slow waves. No significant changes in
      percentage of regular slow waves were noted with the meal or with clonidine (P >
      0.05). In conclusion, the postprandial response of gastric myoelectrical activity
      in dogs to a solid meal is featured with an increase in amplitude and spike
      bursts, which is inhibited by clonidine.

PMID- 11318544
TI  - Association of susceptibility locus for inflammatory bowel disease on chromosome
      16 with both ulcerative colitis and Crohn's disease.
AB  - A susceptibility locus for inflammatory bowel disease (IBD) on chromosome 16
      (IBD1) has been linked to Crohn's disease in genome-wide linkage studies. We
      performed a case-control study with two markers for this locus using leukocyte
      DNA from 127 Crohn's patients, 83 ulcerative colitis patients, and 74 control
      patients. Allele, genotype, and haplotype frequencies of the polymerase chain
      reaction products were determined using autoradiography. Haplotype frequencies
      differed for ulcerative colitis and Crohn's disease, particularly for haplotype
      CC (22% ulcerative colitis vs 10% Crohn's disease, P = 0.002 Chi2 = 10.0) and
      haplotype CD (18% Crohn's disease vs 9% ulcerative colitis, P = 0.025 Chi2 =
      5.02). These data demonstrate the association of the IBD1 locus with both
      ulcerative colitis and Crohn's disease in a group of unrelated IBD patients. The
      use of such microsatellite markers when combined with others, might help
      distinguish ulcerative colitis from Crohn's disease in patients with ambiguous
      clinical and histological features.

PMID- 11318545
TI  - Reduced free protein S levels in patients with inflammatory bowel disease:
      prevalence, clinical relevance, and role of anti-protein S antibodies.
AB  - We evaluated free plasma levels of protein S, a natural anticoagulant factor, the
      prevalence of anti-protein S antibodies, a possible cause of protein S
      deficiency, and their correlation with anti-phospholipid antibodies in 53
      patients with inflammatory bowel disease (IBD) and 53 age- and sex-matched
      controls. Mean free plasma protein S levels (+/- SD) were significantly lower in
      IBD patients (0.98+/-0.32 IU/ml) than in controls (1.06+/-0.28 IU/ml) (P < 0.05);
      only one patient showed protein S deficiency. Specific antibodies to protein S
      were found in four IBD patients (7.5%) and in one control (1.9%) (P = NS). Five
      IBD patients (9.4%) and none of the controls showed anti-phospholipid antibodies
      (P < 0.06). No correlation was found between free protein S levels and anti
      protein S antibodies or between anti-protein S and anti-phospholipid antibodies.
      In conclusion, free plasma protein S levels are slightly but significantly
      decreased in IBD patients. The prevalence of anti-protein S and antiphospholipid
      antibodies is increased in IBD patients. Anti-protein S antibodies do not appear
      to determine low protein S levels or to overlap with or belong to anti
      phospholipid antibodies.

PMID- 11318546
TI  - Predictive value of inflammatory and coagulation parameters in the course of
      severe ulcerative colitis.
AB  - Alterations in markers of coagulation have been found in patients with
      inflammatory bowel disease. Our aim was to study the predictive value of
      coagulation and inflammatory parameters in the course of severe ulcerative
      colitis. Twenty-seven patients were included. The disease course was followed for
      one year. Sensitivity, specificity, negative predictive value, positive
      predictive value, and likelihood ratio, as well as the clinical predictive value
      of laboratory variables were calculated. Inflammatory variables, such as ESR,
      CRP, and leukocyte and platelet count showed poor diagnostic accuracy. Several
      coagulation parameters, such as fibrinogen and fibrin(ogen) degradation products,
      were increased in patients with active ulcerative colitis, whereas coagulation
      factor XIII was decreased. No significant relationship between clinical course
      and coagulation parameters was demonstrated, though both inflammatory and
      coagulation parameters were useful in the assessment of disease activity in
      patients with active ulcerative colitis.

PMID- 11318547
TI  - Serum transglutaminase correlates with endoscopic and histopathologic grading in
      patients with ulcerative colitis.
AB  - Factor XIIIa, a circulating form of transglutaminase, plays a key role in
      intestinal mucosal repair. We found that transglutaminase levels are decreased in
      serum of patients with inflammatory bowel diseases and demonstrated in a rat
      model of chronic colitis that serum transglutaminase is closely related to the
      severity of intestinal damage. We aimed, therefore, to correlate serum
      transglutaminase levels with standard endoscopic and histopathologic grading
      systems in patients affected by ulcerative colitis (UC). In 249 patients with UC,
      we assayed serum transglutaminase activity by a radioenzymatic method and
      measured clinical activity index (CAI) according to modified Rachmilewitz's
      criteria. In a subset of 82 patients undergoing colonoscopy, endoscopic and
      histologic indices were studied. Biopsy specimens were also taken from 28
      patients to measure myeloperoxidase (MPO) as a marker of mucosa inflammation.
      Serum transglutaminase levels significantly correlated with the CAI scoring (r = 
      0.63; P < 0.01); likewise serum transglutaminase showed the best correlation with
      endoscopic (r = -0.71; P < 0.001) and histologic (r = -0.79; P < 0.001) scores.
      Myeloperoxidase activity was significantly higher in patients with active UC than
      those in remission (P < 0.01), showing a significant correlation with serum
      transglutaminase levels (r = -0.68; P < 0.01). Immunohistochemistry showed factor
      XIIIa localization in the extracellular matrix of damaged mucosa. In conclusion,
      these results suggest that transglutaminase assay can be useful in managing UC as
      a serological, noninvasive indicator of intestinal mucosal status.

PMID- 11318548
TI  - Measles virus persistence in specimens of inflammatory bowel disease and autism
      cases.

PMID- 11318549
TI  - Lamina propria lymphocytes produce interferon-gamma and develop suppressor
      activity in response to lactoglobulin.
AB  - This study examines the in vitro response of human lamina propria lymphocytes
      (LPLs) to food antigens. LPLs were obtained from jejunum of healthy individuals
      undergoing gastric bypass operations for morbid obesity. Proliferation was
      assayed by [3H]thymidine incorporation and cytokine production by ELISA. LPLs
      proliferated in response to keyhole limpet hemocyanin, ovalbumin, lactoglobulin,
      and phytohemagglutinin (PHA), but not to yeast. The responses to lactoglobulin
      and PHA were inhibited by the CTLA4/Fc chimera and by MAbs against CD2, CD58,
      CD80, and CD86, indicating stimulation of CD28+ LPLs with antigen-presenting
      cells through activation of the CD2 pathway. Besides producing IL-2, IL-10, and
      TNF-alpha, LPLs synthesized large amounts of IFN-gamma (100 ng/ml) with
      lactoglobulin, a process dependent upon CD80/CD86, CD40/CD40L, and IL-12. After a
      three-day culture with lactoglobulin, ovalbumin, or PHA, LPLs developed
      suppressor activity that reduced proliferation of naive LPLs to these same
      stimuli. In summary, LPLs first respond to lactoglobulin by proliferation and IFN
      gamma production, then by development of antigen nonspecific suppression.

PMID- 11318550
TI  - Gut-associated immunolocalization of the Schistosoma mansoni cysteine proteases,
      SmCL1 and SmCL2.
AB  - Transcripts encoding discrete, cathepsin L-like cysteine proteases, known as
      SmCL1 and SmCL2, have been reported from the adult stages of the human blood
      fluke Schistosoma mansoni. However, the physiological roles of these 2 enzymes
      and their natural substrates remain uncertain and controversial. To determine
      their localization in adult S. mansoni by immunocytochemical procedures, and
      thereby to gain insight into their likely functions, polymerase chain reaction
      based cDNAs encoding mature SmCL1 and SmCL2 were ligated into Escherichia coli.
      The bacterially expressed recombinant proteins (bSmSL1, bSmCL2) were used to
      generate monospecific rabbit antisera. For light microscopy, paraffin-embedded
      sections were visualized with the fluorophore Cy3. For transmission electron
      microscopy (TEM), LR White-embedded tissue was visualized with 15 nm gold. Under
      light microscopy, fluorescence was visible on the luminal surface of the
      gastrodermis in both sexes for both proteins. For bSmCL1 and bSmCL2, TEM revealed
      gold particles primarily associated with amorphous deposits within superficial
      digestive vacuoles on the gastrodermal surface of males and females. Some bSmCL1
      reaction product was observed in vesicles within the gastrodermis, and very
      sparse gastrodermal activity was observed with bSmCL2. By contrast, neither
      enzyme was immunolocalized in the reproductive organs, vitelline glands, nor
      gynecorphoric canal. The gut-associated immunolocalization of SmCL1 and SmCL2
      indicates that both these endopeptidases participate in hemoglobin proteolysis.

PMID- 11318551
TI  - Inhibitors of the lipoxygenase pathway block development of Brugia malayi L3 in
      vitro.
AB  - Brugia malayi L3 molt to the L4 stage in serum-free cultures supplemented with
      arachidonic, linoleic, or linolenic acids and the basidiomycetous yeast
      Rhodotorula minuta. These fatty acids are capable of entering the eicosanoid
      pathway of arachidonate metabolism, the pathway responsible for generating a
      number of biologically active mediators, including prostaglandins, leukotrienes,
      and lipoxins. To determine whether this pathway was required for L3 development,
      we added dual inhibitors of cyclooxygenase and lipoxygenase to in vitro cultures
      containing B. malayi L3. These compounds significantly inhibited L3 molting. To
      evaluate whether 1 or both of these pathways of arachidonate metabolism were
      involved in molting, we tested drugs inhibiting either cyclooxygenase or
      lipoxygenase. Lipoxygenase inhibitors blocked L3 molting, whereas cyclooxygenase
      inhibitors did not. To assess whether enzymes operating downstream of
      lipoxygenase were also involved in L3 molting, we added inhibitors of enzymes
      involved in leukotriene synthesis and found they were also capable of preventing
      development. We tested the same inhibitor panel on Dirofilaria immitis L3. A
      single lipoxygenase inhibitor and inhibitors of 2 different enzymes operating
      downstream of lipoxygenase disrupted D. immitis development. These results
      demonstrate that a lipoxygenase pathway product is required for molting of the
      infective stage larvae of filarial parasites.

PMID- 11318552
TI  - Downstream changes in the composition of the parasite community of fishes in an
      Appalachian stream.
AB  - The spatial distribution of 6 parasite species (Myxobolus sp., Dactylogyrus sp.,
      Sterliadochona ephemeridarum, Plagioporus sinitsini, Allopodocotyle chiliticorum,
      Allocreadium lucyae) was studied in 5 species of fishes (Oncorhynchus mykiss,
      Clinostomus funduloides, Notropis chiliticus, Rhinichthys atratulus, Semotilus
      atromaculatus) in Basin Creek, an Appalachian stream in North Carolina. Nonmetric
      multidimensional scaling and vector fitting were used to determine if the
      proximity of sampling sites was related to community similarity. Position along
      Basin Creek was significantly related to parasite community structure. Breaks in
      parasite community composition were imposed by waterfalls at upstream areas of
      Basin Creek that restricted distributions of C. funduloides, N. chiliticus, and
      S. atromaculatus and at the downstream limit of the study area by a break in the
      distribution of S. ephemeridarum coincident with the existence of a dam but were
      independent of suitable piscine host distributions. These discontinuities in
      parasite community composition imply that the relationship between proximity of
      sites and community similarity is predictive because distance between sites is
      related to the probability that fish at different sampling sites recruit
      parasites from different species pools. This relationship is not the same for all
      component communities.

PMID- 11318553
TI  - Horizontal and vertical ectoparasite transmission of three species of Malophaga,
      and individual variation in european bee-eaters (Merops apiaster).
AB  - Dispersal of avian ectoparasites can occur through either vertical transmission
      from adult birds to their offspring in the nest or through horizontal
      transmission between adult birds or through phoresy. In this study, we
      investigated the importance of the 2 main transmission modes in the colonial
      European bee-eater and examined whether individual differences in ectoparasite
      intensity exist in relation to age, sex, and morphological features of the birds.
      The intensity of 3 chewing lice species was investigated. Almost all adult bee
      eaters (98.3%, n = 176) were infested with 1 of the 3 ectoparasite species,
      whereas only 10.8% (n = 167) of all chicks were infested. Meropoecus meropis was
      the most frequent ectoparasite species on adult bee-eaters (prevalence 94.3%),
      whereas Meromenopon meropis was the most common species on chicks (prevalence
      9.6%). Our results suggest that chewing lice are mainly horizontally transmitted
      among adult bee-eaters and mainly among pair members, whereas vertical
      transmission between parents and nestlings is less frequent. These conclusions
      were supported by a relation in ectoparasite intensity of pair members and a
      parasite removal experiment. Ectoparasite intensity was in general low in
      nestlings and did not correlate with ectoparasite intensity of their parents.
      Host age, sex, weight, and other morphological features did not explain variation
      in chewing lice infestation.

PMID- 11318554
TI  - A new species of sucking louse (Insecta, Anoplura) parasitic on Auliscomys
      (Mammalia, Rodentia) in Argentina.
AB  - Hoplopleura auliscomydis n. sp. is described based on specimens collected from
      Auliscomys micropus (Waterhouse 1837), from Colln Cura, Neuquen Province,
      Argentina. Descriptions are provided for the holotype male, female, first nymphal
      instar, external architecture of eggs (by scanning electron microscopy), and
      sites of oviposition, providing differences from its close relative Hoplopleura
      neotomydis Castro, Gonzalez, and Cicchino, 1995. The geographical ranges of these
      2 species are restricted to the Neuquen Province in Argentina. A key to the 9
      species of the Hoplopleura travassosi species-group recorded in Argentina is also
      given.

PMID- 11318555
TI  - Parasite-induced variation in host morphology: brain-encysting trematodes in
      fathead minnows.
AB  - Metacercariae of the trematode Ornithodiplostomum ptychocheilus cause a
      conspicuous enlargement of the cranium of juvenile fathead minnows (Pimephales
      promelas). Minnows sampled from 2 naturally infected ponds in northern Alberta,
      Canada, had 12% higher and 7% wider craniums compared to fish from an adjacent,
      uninfected pond. We tested the prediction that cranial distortion was caused by
      encystment of metacercariae on the brains of slow-growing minnows in a factorial
      experiment. Juvenile fish were either exposed once to 120 cercariae or 3 times to
      40 cercariae; they were then fed either a low- or high-quantity diet for 8 wk.
      Results showed that after controlling for host size, cranial heights were
      affected by infection regime and host diet but not by the infection x diet
      interaction. Cranial distortion was most prominent in minnows exposed once to
      cercariae, showing that the rapid, simultaneous growth of metacercariae
      interfered with the normal development of the cranium. Thus, the expression of
      the parasite-induced phenotype was context dependent, the result of factors
      associated with the dynamics of cercariae transmission and host growth rate.

PMID- 11318556
TI  - Ultrastructure and chaetotaxy of sensory receptors in the cercariae of a species
      of Crepidostomum Braun, 1900 and Bunodera Railliet, 1896 (Digenea:
      Allocreadiidae).
AB  - Previous investigations of cercarial sensory systems have focused on chaetotaxy
      and ultrastructure of sensory receptors and have revealed chaetotaxic patterns
      within families, genera, and species as well as different types of sensory
      receptors. However, chaetotaxic and ultrastructural observations have rarely been
      combined. We investigated the ultrastructure of cercarial sensory receptors in
      conjunction with the chaetotaxy and neuromorphology in 2 allocreadiid species
      belonging to the genera Crepidostomum and Bunodera. Cercariae were treated with
      acetylthiocholine iodide and silver nitrate, and for scanning electron microscopy
      (SEM) and transmission electron microscopy (TEM). Similar cholinergic nerve
      networks were revealed. Chaetotaxy was consistent with that of other
      allocreadiids. Seven and 6 types of receptors were distinguished with SEM in
      Crepidostomum sp. and Bunodera sp., respectively. Types differed in number of
      cilia (1 or 2), cilium length (short, moderately long, or long), presence or
      absence of a tegumentary collar and a domelike base, and tegumentary collar
      length (low, moderately low, or high), TEM of some types revealed unsheathed
      cilia, basal body, and thickened nerve collars. Some receptor types were site
      specific. Thus, long uniciliated receptors were concentrated on the dorsal
      surface. Other types, such as short uniciliated receptors, were widespread
      throughout most regions. Ultrastructure and site-specificity observations suggest
      that most receptors are mechanoreceptors.

PMID- 11318557
TI  - Identification and the role of soluble antigens detected in bile from Eimeria
      stiedai-infected rabbits.
AB  - Antibodies against Eimeria stiedai sporozoites and merozoites were detected in
      the sera of rabbits immunized with bile obtained from infected rabbits on the
      15th day post-infection. The trails made by gliding sporozoites were also
      detected by the sera. After penetration into the host cell, an antibody-binding
      region was observed on the parasitophorous vacuole membranes of the parasites.
      Rabbits administered a combination of the bile and cholera toxin shed fewer
      oocysts in the feces after infection than control rabbits. The immunized rabbits
      developed a high level of IgA antibody against soluble antigens in the bile. By
      immunoblotting, antigens with molecular masses of 32, 37, and 49 kDa were
      detected in the bile obtained from infected rabbits on the 15th day
      postinfection. Absorption treatment with sporozoites reduced or abolished the
      antibody reactivity to the 32-kDa antigen of merozoites and the bile antigens.
      However, antibody reactivity to the 37- and 49-kDa antigens still remained. These
      results indicate that soluble antigens are present in the bile of rabbits in the
      acute phase of infection, and these may be produced and released by merozoites
      during the host cell invasion process.

PMID- 11318558
TI  - Killing of Schistosoma mansoni sporocysts by hemocytes from resistant
      Biomphalaria glabrata: role of reactive oxygen species.
AB  - The fate of Schistosoma mansoni (Trematoda) sporocysts in its molluscan host
      Biomphalaria glabrata (Gastropoda) is determined by circulating phagocytes
      (hemocytes). When the parasite invades a resistant snail, it is attacked and
      destroyed by hemocytes, whereas in a susceptible host it remains unaffected. We
      used 3 inbred strains of B. glabrata: 13-16-R1 and 10-R2, which are resistant to
      the PR-1 strain of S. mansoni, and M-line Oregon (MO), which is susceptible to PR
      1. In an in vitro killing assay using plasma-free hemocytes from these strains,
      the rate of parasite killing corresponded closely to the rate by which S. mansoni
      sporocysts are killed in vivo. Hemocytes from resistant snails killed more than
      80% of S. mansoni sporocysts within 48 hr, whereas sporocyst mortality in the
      presence of hemocytes from susceptible snails was <10%. Using this in vitro
      assay, we assessed the involvement of reactive oxygen species (ROS) produced by
      resistant hemocytes, during killing of S. mansoni sporocysts. Inhibition of NADPH
      oxidase significantly reduced sporocyst killing by 13-16-R1 hemocytes, indicating
      that ROS play an important role in normal killing. Reduction of hydrogen peroxide
      (H2O2) by including catalase in the killing assay increased parasite viability.
      Reduction of superoxide (O2-), however, by addition of superoxide dismutase or
      scavenging of hydroxyl radicals (*OH) and hypochlorous acid (HOCl) by addition of
      hypotaurine did not alter the rate of sporocyst killing by resistant hemocytes.
      We conclude that H2O2 is the ROS mainly responsible for killing.

PMID- 11318559
TI  - Biotic and abiotic effects on endoparasites infecting Dipodomys and Perognathus
      species.
AB  - Between 1989 and 1998, 3,504 rodents of the genera Dipodomys and Perognathus were
      collected from 4 permanent collecting sites on the University of New Mexico's
      Long Term Ecological Research station, located on the Sevilleta National Wildlife
      Refuge (SNWR), Socorro County. New Mexico. All animals were killed and examined
      for endoparasites (acanthocephalans, cestodes, coccidia, and nematodes). The
      present report focuses on 3 endoparasite groups, cestodes, coccidia, and
      nematodes. Specific analyses address how prevalence changes were related to
      abiotic factors such as habitat, season, or precipitation, and how prevalence of
      each parasite species in each host species differed in relation to host age, host
      sex, host reproductive status, host body mass, host density, parasite-parasite
      interactions, and host specificity. A logistic regression was used to determine
      which host characters and which abiotic factors are correlated with a parasite
      infection. Significant variables for at least half of the parasites include
      season, site, and winter precipitation. However, no parasite prevalences were
      correlated, and significant variables were not identical between parasites,
      indicating that each parasite species varied independently and that no
      generalizations can be drawn. The parasite prevalences in these rodents on the
      SNWR vary in independent and complex ways.

PMID- 11318560
TI  - Sylvatic and domestic Trichinella spp. in wild boars; infectivity, muscle larvae
      distribution, and antibody response.
AB  - Thirty-six wild boars were inoculated with Trichinella spiralis, Trichinella
      nativa, Trichinella britovi, Trichinella pseudospiralis (USSR), T. pseudospiralis
      (USA), T. pseudospiralis (AUST), Trichinella murrelli, Trichinella T6, and
      Trichinella nelsoni. The wild boars were killed at 5 and 10 wk postinoculation
      (PI), and the number of muscle larvae per g (lpg) of tissue was determined for 18
      muscles or muscle groups. Five weeks PI, all Trichinella genotypes had
      established as muscle larvae, but their infectivity varied widely: T. spiralis
      established in high numbers (mean = 296 lpg), T. britovi, T. nelsoni, and 1 of
      the T. pseudospiralis genotypes (AUST) in moderate numbers (mean = 53-74 lpg),
      whereas the remaining genotypes were poorly infective (mean 2-16 lpg). Because of
      considerable weight gain of the wild boars, an estimated total larval burden
      (live weight x lpg) was calculated for each animal. The total larval burden did
      not change significantly over time for T. spiralis, T. murrelli, T. britovi, T.
      nelsoni, and T. pseudospiralis (USA and USSR), whereas a significant reduction
      could be demonstrated for T. nativa, Trichinella T6, and T. pseudospiralis
      (AUST). Diaphragm and tongue were predilection sites in wild boars, independent
      of Trichinella genotype and infection level. At low infection levels, a greater
      percentage of larvae were found in diaphragm and tongue at 10 wk than 5 wk PI.
      Antibody responses increased rapidly between weeks 3 and 5 PI. For T. spiralis
      and T. nelsoni, the high antibody level persisted throughout the experimental
      period, but for T. nativa, T. britovi, T. murrelli, or Trichinella T6, the levels
      declined. For T. pseudospiralis, the antibody response increased more gradually
      between weeks 3 to 10 PI. Infection with all genotypes of Trichinella were
      detected using any of 7 excretory-secretory antigens, which points to the
      potential use of 1 common antigen for epidemiological studies on Trichinella in
      wild boars. In conclusion, T. spiralis is highly infective to wild boars, T.
      britovi, T. nelsoni, T. pseudospiralis (USA), and T. pseudospiralis (USSR) are
      moderately infective, and T. nativa, T. murrelli, T. pseudospiralis (AUST), and
      Trichinella T6 are poorly adapted to this host species.

PMID- 11318561
TI  - The effects of Myxobolus cerebralis myxospore dose on triactinomyxon production
      and biology of Tubifex tubifex from two geographic regions.
AB  - The aquatic oligochaete Tubifex tubifex is an obligate host of Myxobolus
      cerebralis, the causative agent of salmonid whirling disease. Tubifex tubifex can
      become infected by ingesting myxospores of M. cerebralis that have been released
      into sediments upon death and decomposition of infected salmonids. Infected worms
      release triactinomyxons into the water column that then infect salmonids. How the
      dose of myxospores ingested by T. tubifex influences parasite proliferation and
      the worm host are not well understood. Using replicated laboratory experiments,
      we examined how differing doses of myxospores (50, 500, 1,000 per worm)
      influenced triactinomyxon production and biomass, abundance, and individual
      weight of 2 geographically distinct populations of T. tubifex. Worm populations
      produced differing numbers of triactinomyxons, but, within a population, the
      production did not differ among myxospore doses. At the lowest myxospore dose, 1
      worm population produced 45 times more triactinomyxons than myxospores received,
      whereas the other produced only 6 times more triactinomyxons than myxospores.
      Moreover, total T. tubifex biomass, abundance, and individual weight were lower
      among worms receiving myxospores than in myxospore-free controls. Thus, T.
      tubifex populations differ in ability to support the replication of M.
      cerebralis, and infection has measurable consequences on fitness of the worm
      host. These results suggest that variability in whirling disease severity
      observed in wild salmonid populations may partially be attributed to differences
      in T. tubifex populations.

PMID- 11318562
TI  - Seasonal prevalence of third-stage larvae of Dirofilaria immitis in mosquitoes
      from Florida and Louisiana.
AB  - Heads of 109,597 mosquitoes collected during 1996 and 1997 from Gainesville,
      Florida (1996, n = 39,131; 1997, = 34,209), Bartow, Florida (1996, n = 12,000;
      1997, n = 12,000), and Baton Rouge, Louisiana (1996, n = 12,257) were tested by a
      polymerase chain reaction and Southern hybridization-based test for the presence
      of third-stage larvae of the canine heartworm Dirofilaria immitis. Mosquito heads
      were pooled (1-200 heads) by month, locality, and species for testing. The test
      used was species specific for D. immitis and was capable of detecting DNA from a
      single larva in a pool of 200 mosquito heads. Specificity for the third larval
      stage was achieved by probing only mosquito heads. One or more D. immitis
      infected mosquito heads were detected in each month of the year from Barrow in
      both 1996 and 1997. No infected mosquito heads were detected from Gainesville or
      Baton Rouge in December, January, February, or March. These results are in
      general agreement with previous sentinel dog and model prediction studies that
      showed heartworm transmission in the warm temperate Gulf coast region of the
      United States to be seasonal rather than continuous as previously believed.

PMID- 11318563
TI  - A comparison of biological performances among a laboratory-isolated population
      and two wild populations of Moniliformis moniliformis.
AB  - Divergence of biological performance of a laboratory-reared population of
      Moniliformis moniliformis (Acanthocephala) was investigated after 31 yr, or
      approximately 60 generations, of genetic isolation. An isolate of the laboratory
      reared population and isolates of 2 wild populations were used to begin 3
      independent life cycles that were maintained for 1 generation for interbreeding
      and life history trait comparison. Both wild population isolates represented
      populations with open gene flow. One wild population isolate represented a
      present-day sample of descendants of the parent population of the laboratory
      isolate. All 3 populations hybridized, and egg production occurred in all mixed
      sex pairs of different populations. The 3 populations did not differ
      significantly in prepatent period, mean daily egg production, or establishment
      within the definitive host Rattus norvegicus. The 3 populations varied in patent
      period, but the laboratory-isolated worms differed from the 2 wild population
      isolates no more than they did from each other. A positive correlation between
      mean daily egg production and duration of patent period resulted in different
      cumulative egg productions. A 31-yr period of isolation did not produce greater
      divergence in a laboratory population of M. moniliformis than occurs between wild
      populations with respect to the biological parameters measured.

PMID- 11318564
TI  - Falcaustra lowei n. sp. and other helminths from the Tarahumara frog, Rana
      tarahumarae (Anura: Ranidae), from Sonora, Mexico.
AB  - Seventy-four specimens of Falcaustra lowei n. sp. were recovered from the
      intestines of 9 of 42 (21%) Tarahumara frogs. Rana tarahumarae, from Sonora,
      Mexico. F. lowei is the 14th Nearctic species to be described and belongs to that
      group of species possessing a pseudosucker, namely F. catesbeianae, F. chabaudi,
      F. chelydrae, F. mexicana, and F. wardi. The new species can be readily
      differentiated from these by the arrangement of caudal papillae and length of
      spicules. Priority description of F. affinis is established and F. concinnae is
      removed from synonymy with F. affinis. In addition to F. lowei, 3 species of
      Digenea, Glypthelmins quieta, Haematoloechus breviplexus, Langeronia macrocirra;
      1 species of Eucestoda, Ophiotaenia magna; 7 species of Nematoda, F. inglisi,
      Foleyellides striatus, Oswaldocruzia pipiens, Rhabdias ranae, Subulascaris
      falcaustriformis, Physaloptera sp. (larvae): and 1 species of Acanthocephala, an
      unidentified oligacanthorhynchid cystacanth, were found.

PMID- 11318565
TI  - Characterization of the Oregon isolate of Neospora hughesi from a horse.
AB  - Neospora hughesi was isolated in cell cultures inoculated with homogenate of
      spinal cord from a horse in Oregon. Tachyzoites of this Oregon isolate of N.
      hughesi were maintained continuously by cell culture passage and tachyzoites were
      infective to immunosuppressed mice. Gamma interferon gene knockout (KO) mice
      injected with tachyzoites developed fatal myocarditis and numerous tachyzoites
      were seen in lesions. Gerbils (Meriones unguiculatus) inoculated with tachyzoites
      developed antibodies (> or = 1:500) as indicated by the Neospora caninum
      agglutination test but did not develop clinical signs, and Neospora organisms
      were not demonstrable in their tissues. Tissue cysts were not found in gerbils,
      nude mice, KO mice, immunosuppressed outbred Swiss Webster mice, or BALB/c mice
      injected with the Oregon isolate of N. hughesi. Ultrastructurally, tachyzoites of
      the Oregon isolate from the myocardium of infected KO mice and from cell culture
      were similar to N. caninum tachyzoites. Western blot analysis using NcSAG1 and
      NcSRS2 polyclonal and monoclonal antibodies and characterization of the internal
      transcribed spacer 1 sequences from the equine isolates and different isolates of
      N. caninum from dogs and cattle indicated that the Oregon isolate of N. hughesi
      is distinct from N. caninum isolates from cattle and dogs.

PMID- 11318566
TI  - Four new species of Acanthobothrium (Cestoda: Tetraphyllidea) from the whiptail
      stingray Dasyatis brevis in the Gulf of California, Mexico.
AB  - Examination of the spiral intestines of 29 whiptail stingrays, Dasyatis brevis,
      from 6 sites in the Gulf of California, Mexico in 1993 and 1996 resulted in the
      discovery of 4 new species of Acanthobothrium: Acanthobothrium bullardi,
      Acanthobothrium dasi, Acanthobothrium rajivi, and Acanthobothrium soberoni. This
      brings the total number of species of Acanthobothrium known from the eastern
      Pacific Ocean to 34. With 22 additional species reported from elasmobranchs from
      the western Atlantic Ocean, and over 100 species globally, the number of
      interspecific comparisons required to justify the designation of a new species is
      rather unwieldy. To facilitate these and future comparisons, and in the absence
      of a phylogenetic hypothesis for this genus, the 56 species of Acanthobothrium
      from these 2 geographic regions were categorized for 4 characters: total length
      (< or = or > 15 mm), number of segments (< or = or > 50 segments), number of
      testes (< or = or > 80), and symmetry of poral and aporal ovarian lobes. These 56
      taxa and their categories are presented in tabular form. Based on these
      characters, A. bullardi, A. dasi, and A. rajivi are category 2 species (they are
      relatively small, possess few segments, relatively few testes, and exhibit
      asymmetrical ovaries); A. soberoni is a category 6 species (it is a relatively
      longer worm with a larger number of segments, but with fewer testes and an
      asymmetrical ovary). All 4 species differ from 1 another and from species in
      other geographic regions in further subtleties of these 4 characters as well as
      hook size and relative length of hook prongs, cirrus sac size, genital pore
      position, number of columns of testes anterior to the cirrus sac, and number of
      postvaginal testes. Five specimens that appear to represent a new species of
      Acanthobothroides were also collected. This species is figured and some details
      of the morphology are described, but the material was considered to be
      insufficient to allow for formal description of this species at this time. This
      is the first record of either of these genera of onchobothriid tapeworms from the
      Gulf of California.

PMID- 11318567
TI  - Description and epidemiology of Theileria youngi n. sp. from a northern
      Californian dusky-footed woodrat (Neotoma Fuscipes) population.
AB  - An epidemiologic study designed to identify the small mammal reservoir for the
      zoonotic WA1-type babesial parasite resulted in the discovery of a small,
      intraerythrocytic piroplasm in smeared blood from dusky-footed woodrats (Neotoma
      fuscipes) in northern California. The woodrat parasites were isolated and
      compared to other piroplasm parasites based on their morphology, antigenicity,
      and genetic characteristics. These studies indicated that the woodrat parasites
      were not the WA1-type babesial agent but were of the genus Theileria. We
      accordingly named it Theileria youngi. The prevalence in the woodrat population
      was high (61%). Infection was unrelated to gender or age of the woodrats.
      Potential vectors for this tick-transmitted parasite included 3 species of ticks
      recovered from the woodrats. Dermacentor occidentalis, Ixodes woodi, and Ixodes
      pacificus. Mostly larval or nymphal stages were recovered, suggesting
      transstadial transmission is possible. This is the first piroplasm fully
      characterized from a dusky-footed woodrat.

PMID- 11318568
TI  - Patterns of occurrence and 18S rDNA sequence variation of PKX (Tetracapsula
      bryosalmonae), the causative agent of salmonid proliferative kidney disease.
AB  - Recent progress in understanding the etiology of proliferative kidney disease
      (PKD) includes the identification of freshwater bryozoans as the natural hosts of
      the myxozoan parasite that causes the disease in salmonid fish and formal
      description of the parasite as Tetracapsula bryosalmonae. This paper presents
      data on patterns of occurrence of T. bryosalmonae and sequence variation among
      isolates. T. bryosalmonae infects bryozoans that range from primitive to more
      derived genera within the Phylactolaemata and that differ in growth form and
      habits. Infected bryozoans have been collected in diverse habitats including
      cold, clear streams and warm, eutrophic lakes. Temporal surveys reveal intra- and
      interannual variation in infection levels, and spatial variation in incidence of
      infection is implicit by the apparent absence of T. bryosalmonae from many
      bryozoan populations. The significance of minor variation in partial sequences of
      18S rDNA requires further investigation. The information presented here provides
      the first significant insights into the ecology of T. bryosalmonae.

PMID- 11318569
TI  - Phylogenetic analysis of Alloglossidium (Digenea: Macroderoididae) and related
      genera: life-cycle evolution and taxonomic revision.
AB  - A phylogenetic analysis was performed on 13 species of digenetic trematodes in
      the Macroderoididae, including 10 species of Alloglossidium, 2 species of
      Alloglossoides, and Hirudicolotrema richardsoni. The evolution of the unusual
      life-cycle patterns in the group was assessed in light of the proposed phylogeny.
      The results support previous hypotheses that taxa with a 3-host life cycle
      involving catfish as definitive hosts are basal to taxa with a 2-host life cycle
      involving invertebrates such as crustaceans and leeches as definitive hosts. Our
      results also strongly suggest that species maturing in leeches evolved from an
      ancestor that matured in crustaceans. Our phylogeny places Alloglossoides and
      Hirudicolotrema within Alloglossidium, showing Alloglossidium to be paraphyletic.
      To achieve a natural classification, Alloglossoides and Hirudicolotrema are
      synonymized with Alloglossidium, and a revised generic diagnosis for
      Alloglossidium is given.

PMID- 11318570
TI  - Philureter trigoniopsis, a new genus and species (Dactylogyridae,
      Ancyrocephalinae) from the ureters and urinary bladder of Galaxias maculatus
      (Osmeriformes: Galaxiidae) in Patagonia (Argentina).
AB  - The monotypic Philureter n. gen. (Ancyrocephalinae; Dactylogyridae) is proposed
      to accommodate Philureter trigoniopsis n. sp. with the following features:
      presence of a cuplike ventral haptor armed with 14 hooks and 2 anchor/bar
      complexes; dorsal pair of anchors poorly defined and variable in shape, 1
      frequently absent; tandem, intercecal gonads, testis bilaterally lobulated.
      Philureter trigoniopsis n. sp. is described from the ureters and urinary bladder
      of Galaxias maculatus (Jenyns, 1842) (Osmeriformes) in Patagonian Andean lakes,
      Argentina.

PMID- 11318571
TI  - Specific detection of Neospora caninum oocysts in fecal samples from
      experimentally-infected dogs using the polymerase chain reaction.
AB  - Neospora caninum oocysts, passed in the feces of a definitive host (dog), were
      isolated, and genomic DNA was extracted. A polymerase cahin reaction (PCR)
      targeting the N. caninum-specific Nc 5 genomic sequence was performed using the
      isolated DNA. A synthesized competitor molecule containing part of the Nc 5
      sequence was included in the assay as a check against false-negative PCR results
      and to quantify N. caninum oocyst DNA in fecal samples. A standard curve of the
      ratio of fluorescence intensity of PCR-amplified competitor to that of oocyst DNA
      was constructed to compare oocyst equivalents from fecal samples containing
      unknown numbers of N. caninum oocysts and to assess the sensitivity of the assay.
      The specificity of the assay was determined using the Nc 5-specific primers in
      PCR assays against other parasites likely to be found in canine feces. Genomic
      DNA sequences from the canine coccidians Hammondia heydorni, Cryptosporidium
      parvum, Sarcocystis cruzi, S. tenella, and Isospora ohioensis and the canine
      helminth parasites Strongyloides stercoralis, Toxocara canis, Dipylidium caninum,
      and Ancylostoma caninum were not amplified. In addition, genomic DNA sequences
      from oocysts of coccidian parasites that might contaminate dog feces, such as
      Hammondia hammondi, Toxoplasma gondii, or Eimeria tenella, were not amplified in
      the PCR assay. The assay should be useful in epidemiological surveys of both
      domestic and wild canine hosts and in investigations of oocyst biology in
      experimental infections.

PMID- 11318572
TI  - Effect of jasplakinolide on the growth, encystation, and actin cytoskeleton of
      Entamoeba histolytica and Entamoeba invadens.
AB  - The effect of jasplakinolide. an actin-polymerizing and filament-stabilizing
      drug, on the growth, encystation, and actin cytoskeleton of Entamoeba histolytica
      and Entamoeba invadens was examined. Jasplakinolide inhibited the growth of E.
      histolytica strain HM-1:IMSS and E. invadens strain IP-1 in a concentration
      dependent manner, the latter being more resistant to the drug. The inhibitory
      effect of jasplakinolide on the growth of E. histolytica trophozoites was
      reversed by removal of the drug after exposure to 1 microM for 1 day. Encystation
      of E. invadens as induced in vitro was also inhibited by jasplakinolide.
      Trophozoites exposed to jasplakinolide in encystation medium for 1 day did not
      encyst after removal of the drug, whereas those exposed to the drug in growth
      medium for 7 days did encyst without the drug. The process of cyst maturation was
      unaffected by jasplakinolide. Large round structures were formed in trophozoites
      of both amoebae grown with jasplakinolide; these were identified as F-actin
      aggregates by staining with fluorescent phalloidin. Accumulation in trophozoites
      of both amoebae of actin aggregates was observed after culture in jasplakinolide.
      Also, E. invadens cysts formed from trophozoites treated with jasplakinolide
      contained the actin aggregate. Sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis and immunoblot analysis revealed that the jasplakinolide
      treatment led to an increase in the proportion of F-actin associated with
      formation of the aggregate. The results suggest that aggregates are formed from
      the cortical flow of F-actin filaments, and that these filaments would normally
      be depolymerized but are artificially stabilized by jasplakinolide binding.

PMID- 11318573
TI  - Quantification of Cryptosporidium parvum oocysts in mouse fecal specimens using
      immunomagnetic particles and two-color flow cytometry.
AB  - Although single-color flow cytometry has been shown to be more sensitive than
      fluorescence microscopy for the quantification of Cryptosporidium parvum oocysts,
      this method has not been optimized. Monoclonal antibody OW50, specific to the
      cell wall of oocysts, was conjugated to superparamagnetic particles, to
      fluorescein isothiocyanate, and to r-phycoerythrin. The oocysts were then double
      stained with the fluorochrome-labeled OW50 and were placed in tubes with known
      numbers of highly fluorescent polystyrene beads, allowing quantification of the
      oocysts without dependence on acquired sample volume by flow cytometry. Data from
      2-color flow cytometry using logical gating of the oocysts and beads showed a
      linear relationship between dilutions of a purified oocyst suspension and the
      mean numbers of oocysts detected (r2 = 1.00). An average of 15 purified
      oocysts/ml were counted in a dilution with a theoretical concentration of 12
      oocysts/ml. Known numbers of purified oocysts were seeded into normal mouse fecal
      specimens, captured by OW50-labeled immunomagnetic particles, eluted with 5%
      potassium dichromate at low pH, and double stained with fluorochrome-labeled
      OW50. By flow cytometry, the mean recovery was 43.1% (+/-8.3%), and as few as 133
      oocysts were detected. The captured and eluted oocysts were infective in neonatal
      BALB/c mice. This 2-color flow cytometry method, used in conjunction with the
      capture and elution of oocysts by and from immunomagnetic particles, provides a
      powerful tool for not only the quantification and purification of C. parvum
      oocysts from different sources but also for the characterization of oocysts in
      vitro and in vivo.

PMID- 11318574
TI  - A comparative study of different albendazole and mebendazole regimens for the
      treatment of intestinal infections in school children of Usigu Division, western
      Kenya.
AB  - A clinical trial to compare the effectiveness of 4- and 6-mo repeated treatment
      with albendazole 600 mg (Zentel, SmithKline Beecham) or mebendazole 600 mg
      (Vermox, Janssen) on geohelminth infections was carried out on children in 6
      primary schools; the study included 1,186 children, ages 4 to 19 yr. Kato-Katz
      examination was performed on stool samples before and after treatment. Overall,
      albendazole produced better cure rates and egg reduction rates for geohelminths.
      The cure rates for albendazole were 92.4% for hookworm infection, 83.5% for
      Ascaris lumbricoides, and 67.8% for Trichuris trichiura. Mebendazole given either
      2 or 3 times in a year had cure rates of 50 and 55.0% (respectively) for
      hookworm, 79.6 and 97.5% for A. lumbricoides, and 60.6 and 68.3% for T. trichiura
      infection. The geometric mean intensity of hookworm eggs per gram (epg) of stool
      decreased by 96.7% after albendazole treatment compared with 66.3 and 85.1%,
      respectively, for 2 or 3 doses of mebendazole (P < 0.05) over the same period.
      Reductions in epg for A. lumbricoides and T. trichiura were comparable for both
      drugs. Our results indicate that treatment with albendazole at a 6-mo interval
      was more effective than mebendazole regimens and may be the best choice for use
      in the control of the 3 geohelminths.

PMID- 11318575
TI  - Systemic efficacy of nodulisporic acid against fleas on dogs.
AB  - Nodulisporic acid A (NSA) is a novel natural product from a new structural class
      that was shown previously to have insecticidal activity against blowfly larvae.
      To determine if there was useful systemic efficacy against fleas (Ctenocephalides
      felis). NSA was evaluated in an artificial membrane flea feeding device and in
      dogs. In the artificial membrane flea feeding device, adult C. felis were allowed
      to feed on bovine blood containing various concentrations of NSA through a
      Parafilm membrane. NSA killed the fleas with a 50% lethal concentration of 0.68
      microg/ml and was approximately 10-fold more potent than the systemic insecticide
      ivermectin. In the initial probe dog test, a single beagle was challenged with
      100 C. felis before oral dosing with 15 mg/kg of NSA. Flea counts conducted at 72
      hr postdosing showed an 88% reduction relative to control. Re-challenge of the
      same dog at 5 days postdosing showed 50% reduction of fleas at day 7,
      demonstrating some residual flea activity. In a confirmatory study, 8 dogs were
      challenged with 100 fleas just before oral dosing with 15 mg/kg of NSA (4 dogs)
      or vehicle (4 dogs). There was 99% reduction of fleas at 48 hr postdosing in the
      NSA-treated dogs relative to control. Additional challenges with 100 fleas were
      performed on these 8 dogs at 48-hr intervals to determine the duration of
      efficacy, and there was 97, 51, and 0% reduction of fleas relative to control on
      days 4, 6, and 8, respectively. No adverse effects were observed in the dogs in
      these studies. These data show that NSA has potent oral activity in the dog for
      the control of fleas, while lacking overt mammalian toxicity.

PMID- 11318576
TI  - Efficacy of praziquantel in treating natural schistosome infections in common
      mergansers.
AB  - Fifty-one common mergansers were captured on Douglas Lake (Cheboygan County,
      Michigan) and their avian schistosome loads were determined by fecal examination.
      Each bird was given a single dose of 0, 40, or 200 mg/kg of body weight of
      praziquantel and released. All birds were recaptured within 10 days of drug
      administration to determine posttreatment schistosome loads. Only the highest
      dose of praziquantel was found to significantly reduce avian schistosome loads.
      The potential use of praziquantel in swimmer's itch control programs is
      discussed.

PMID- 11318577
TI  - Identification of fatty acid molecules in a Fasciola hepatica immunoprophylactic
      fatty acid-binding protein.
AB  - Fasciola hepatica adult flukes have a native protein complex denoted nFh12 and
      consisting of fatty acid binding proteins that comprise at least 8 isoforms. It
      is a potent immunogen because in several animal hosts it induces an early
      antibody response to F. hepatica infection. It is also a potent cross-protective
      immunogen because it induces a protective immune response in mice to challenge
      infection with Schistosoma mansoni cercariae. The gene encoding this protein has
      been cloned and sequenced. It produces a polypeptide of 132 amino acids with a
      predicted molecular mass of 14.7 kDa and is denoted rFh15. It also has a
      significant homology to a 14-kDa S. mansoni fatty acid binding protein (Sm14). In
      the present study, nFh12 was delipidated with charcoal treatment and then studied
      by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Additionally, a
      lipid analysis of nFh12 was undertaken using gas chromatography-mass spectrometry
      to demonstrate that the nFh12 protein complex is, in fact, a complex of fatty
      acid binding proteins. Five long-chain saturated and unsaturated fatty acids were
      detected. The most abundant were palmitic acid (38%), stearic acid (24%), and
      oleic acid (13%). These fatty acid molecules do not have covalent bonds attached
      to the protein molecule. Because both nFh12 and Sm14 protect mice against
      challenge infection with F. hepatica and S. mansoni, it is possible that they
      have common protective epitopes in which fatty acids could be involved. Further
      studies are in progress to determine the chemical nature of these potential
      common epitopes.

PMID- 11318578
TI  - Myosin diversity in Apicomplexa.
AB  - A polymerase chain reaction (PCR) screen was used to examine the diversity of
      myosins in 7 Apicomplexan parasites: Toxoplasma gondii, Plasmodium falciparum,
      Neospora caninum, Eimeria tenella, Sarcocystis muris, Babesia bovis, and
      Cryptosporidium parvum. Using degenerate PCR primers compatible with the majority
      of known myosin classes, putative myosin sequences were obtained from all of
      these species. All of the sequences obtained showed greatest similarity to
      previously identified apicomplexan myosins, suggesting that the diversity of
      myosins in these parasites is limited. Myosin classes that are known to be
      widespread across the phylogenetic spectrum, e.g., the myosins I, II, and V, were
      not seen in the Apicomplexa. Thus, like the plants, the Apicomplexa may have
      evolved their own unique cohort of myosins that are responsible for the myosin
      driven cellular functions observed in these parasites.

PMID- 11318579
TI  - A simple technique to concentrate the protozoan Mikrocytos mackini, causative
      agent of Denman Island Disease in oysters.
AB  - This report describes a simple filtration technique to isolate the parasite
      Mikrocytos mackini from oyster tissue. The technique is based on successive
      filtration through filter papers and polycarbonate membrane filters of decreasing
      mesh using a low vacuum (<8 cm Hg). This technique allows for the recovery of
      about 1 x 10(8) parasites (microcells) from about 2 g of heavily infected oyster
      tissue. About 99% of the particulate material in the final preparation consisted
      of intact M. mackini.

PMID- 11318580
TI  - Naturally-occurring Neospora caninum infection in an adult sheep and her twin
      fetuses.
AB  - Neospora caninum tissue cysts were found in the brains of surgically delivered
      twin fetuses at 119 days of gestation. In the brains of both fetuses, there was
      an inflammatory reaction involving perivascular cuffings of mononuclear cells,
      glial nodules. The dam of these fetuses died because of metritis.
      Histopathological examination of the ewe revealed N. caninum tissue cysts and
      focal gliosis with mononuclear cell cuffings. A N. caninum-specific DNA fragment
      was detected in a brain homogenate of the ewe by the polymerase chain reaction
      method. This is the first report of N. caninum infection in twin ovine fetuses
      and in an adult sheep.

PMID- 11318581
TI  - A genotypically unique Babesia gibsoni-like parasite recovered from a dog in
      Oklahoma.
AB  - A small Babesia gibsoni-like parasite was identified and isolated as the cause of
      clinical babesiosis in a dog from Oklahoma. Because this was potentially the
      first documented case of B. gibsoni infection in Oklahoma, further
      characterization was warranted, and the 18S nuclear small subunit ribosomal RNA
      gene was sequenced. Sequence comparison with other piroplasms from dogs showed
      significant nucleotide sequence differences between this isolate and both B.
      canis and B. gibsoni. These findings demonstrate that in domestic dogs in North
      America there are at least 2 "small" B. gibsoni-like organisms with distinct
      nucleotide sequences and that the geographic distribution of the "small" canine
      Babesia species may be wider than previously recognized.

PMID- 11318582
TI  - Prevalence of Toxoplasma gondii antibodies in barren-ground caribou (Rangifer
      tarandus groenlandicus) from the Canadian Arctic.
AB  - Prevalence of antibodies to Toxoplasma gondii was determined in 147 barren-ground
      caribou (Rangifer tarandus groenlandicus) from 5 herds in the Northwest
      Territories and Nunavut, northern Canada, by the modified agglutination test
      (MAT). In the mainland herds (Bluenose, Bathurst, and Beverly), antibodies were
      found in 43 (37%) of 117 caribou, and MAT titers were 1:25 in 10, 1:50 in 24, and
      1:500 in 9. In the island herds, only 1 (4.3%) of 23 animals sampled from the
      North Baffin Island herd was positive (titer = 1:25) and no antibodies were
      detected in 7 caribou from the Dolphin and Union herd. The high prevalence of
      antibodies to T. gondii in the mainland caribou herds indicates that caribou meat
      may contain viable T. gondii.

PMID- 11318583
TI  - Estimating transmission potential in gastrointestinal nematodes (order:
      Strongylida).
AB  - Microparasite virulence (the potential to cause harm in the host) is thought to
      be regulated by a direct trade-off with pathogen transmission potential, but it
      is unclear whether similar trade-offs occur in macroparasites (helminths). In
      this analysis, the transmission potentials of 5 nematode species (order
      Strongylida), known to differ in their virulence, were estimated using an index
      based on egg production and larval survivability. Virulence estimates were based
      on the minimum number of worms that cause host death. In nematode species where
      mature adults cause pathology (trichonematidic development), there is a direct
      relationship between virulence and transmission, suggesting that high virulence
      is related to parasite fitness in these worms. However, in nematodes where the
      juvenile stages produce pathology during migration and development (strongylidic
      development), virulence is not correlated with transmission. These data suggest
      that trade-offs between transmission and virulence in nematode parasites are not
      analogous for all species and may depend on the developmental strategy and
      mechanism of pathogenicity of the parasites.

PMID- 11318584
TI  - Antibody levels in goats fed Toxoplasma gondii oocysts.
AB  - Outbred goats were fed 10(5) Toxoplasma gondii oocysts and were monitored twice
      weekly for 8 wk for rectal temperature, clinical signs, parasitemia, and antibody
      levels by indirect fluorescence antibody test (IFAT), latex agglutination test
      (LAT), and indirect enzyme-linked immunosorbent assay (ELISA). After 8 wk, all
      goats were killed, and samples of heart, skeletal muscle, brain, lymph nodes,
      kidneys, and liver were bioassayed in mice. Anorexia, fever, and lethargy were
      observed from day 3 to day 7 postinfection (PI). Parasitemia was detected by
      bioassay in 50% of infected goats from day 7 to day 14 PI. Viable T. gondii
      organisms were isolated from all infected goats. Antibodies to T. gondii were
      detected in some animals on day 10 PI by IFAT and LAT and on day 14 PI by ELISA.
      The infected goats were seropositive on day 17 PI.

PMID- 11318585
TI  - Organ infectivity of Toxoplasma gondii in interferon-gamma knockout mice.
AB  - To determine the influence of interferon (IFN)-gamma on the organ infectivity and
      on the genetic susceptibility of susceptible (C57BL/6) and resistant (BALB/c)
      strains after peroral infection with cysts of Toxoplasma gondii. IFN-gamma
      knockout (KO) mice in C57BL/6 and BALB/c backgrounds were utilized. The kinetics
      of the changes in T. gondii abundance were evaluated with a quantitative
      competitive polymerase chain reaction assay in various organs at different times
      after peroral infection. In IFN-gamma KO mice, a T. gondii-specific gene, SAG1,
      was detected in all organs examined, and the protozoan proliferated much more
      actively than in wild-type mice. The abundance of T. gondii was much higher in
      mesenteric lymph nodes and the heart than in other organs. In contrast, in the
      nervous system organs and kidneys, only a weakly detectable reaction was
      observed. Toxoplasma gondii grew at a more rapid rate in the organs of IFN-gamma
      KO C57BL/6 mice than in the organs of IFN-gamma KO BALB/c mice during the course
      of infection. Destruction of the IFN-gamma gene showed remarkable effects on the
      infectivity in both susceptible and resistant mice.

PMID- 11318586
TI  - Effect of refrigeration on the antinematodal efficacy of ivermectin.
AB  - Several observations have suggested that the anthelmintic ivermectin can affect
      nematodes by non-oral entry into the nematode body. To investigate this
      possibility further, we refrigerated Caenorhabditis elegans at 5 C to prevent its
      locomotion and to block the pharyngeal pumping that is so prominent a feature of
      its feeding. Worms were exposed to ivermectin (1-25 microg/ml) at that
      temperature for 1 hr, after which the medium was replaced by unmedicated medium
      at room temperature. After 1 hr at room temperature the worms were examined and
      counted to determine the degree to which irreversible immobilization had
      occurred. The drug was significantly less effective at 5 C than at room
      temperature. This reduction in potency could be attributed to a general cold
      induced decline in the rate of the biochemical processes involved in drug action.
      Alternatively, the reduction could be attributed to the cold-induced blockade of
      pharyngeal pumping, which would suggest that the efficacy of ivermectin is
      partially the result of oral intake of drug. The fact that antinematodal efficacy
      was not entirely abrogated and reached a significant level despite blockade of
      pharyngeal pumping supports the former interpretation and is in accord with
      earlier indications that ivermectin can enter by non-oral routes. This conclusion
      is further supported by the observation that ivermectin is active against the
      nonfeeding third-stage larva of Haemonchus contortus.

PMID- 11318587
TI  - Susceptibility of avian hosts to experimental Gymnophalloides seoi infection.
AB  - To determine whether avian species are susceptible to infection with
      Gymnophalloides seoi (a human-infecting intestinal trematode), we exposed 7
      species of birds with metacercariae obtained from oysters. The birds were
      necropsied at days 2, 4, and 6 postinfection (PI). The highest worm recovery at
      day 6 PI was obtained from the Kentish plover (Charadrius alexandrinus; mean =
      56.0%), followed by the Mongolian plover (C. mongolus; 49.3%), and the grey
      plover (Pluvialis squatarola; 32.3%). In contrast, no mature worms were recovered
      from the great knot (Calidris tenuirostris), dunlin (C. alpina), black-tailed
      gull (Larus crassirostris), and mallard (Anas platyrhynchos). Among the plovers,
      the worms attained the greatest size at day 6 PI (254.1 x 190.4 microm) in the
      Kentish plover, with a significantly higher number of eggs in the uterus. The 3
      species of plovers are highly susceptible to experimental G. seoi infection,
      suggesting that they could play a role as definitive hosts for these worms in
      nature.

PMID- 11318588
TI  - Effect of iron on the virulence of Trichomonas vaginalis.
AB  - The role of iron was evaluated with respect to the virulence of Trichomonas
      vaginalis in mice. Iron-supplemented and iron-depleted Diamond's trypticase-yeast
      extract-maltose (TYM) media were prepared by adding 360 microM of ferrous sulfate
      and 100 microM of 2,2'-dipyridyl. Trophozoites cultivated from normal TYM and
      iron-supplemented TYM media produced subcutaneous abscesses; however,
      trichomonads grown in an iron-deficient TYM medium failed to produce any
      pathology. In addition to the increased virulence of trophozoites in mice, iron
      affects the level of adherence and the cytotoxicity of trichomonads to HeLa
      cells, which are significantly reduced in trophozoites grown in iron-deficient
      medium. In conclusion, it is suggested that under iron-depleted conditions such
      as that induced by 2,2'-dipyridyl the virulence of T. vaginalis is reduced.

PMID- 11318589
TI  - Effect of miracidial dose on adoptively transferred resistance to Schistosoma
      mansoni in the snail intermediate host, Biomphalaria glabrata.
AB  - Adoptively transferred resistance to Schistosoma mansoni in the snail
      intermediate host Biomphalaria glabrata was measured as a function of miracidial
      challenge dose. Schistosome-susceptible snails implanted with the amebocyte
      producing organ (APO) from resistant donors showed 29 and 39% prevalences of
      infection after challenge with 5 and 10 miracidia, respectively, but 68-83%
      prevalences when exposed to 25-200 miracidia. Prevalences in control (untampered)
      susceptible snails ranged from 97 to 100% at the different miracidial doses.
      Higher infection prevalences at elevated doses suggest that a range of
      transferred resistance occurs and possibly that low levels of APO-derived plasma
      factors or hemocytes in some recipients can be overwhelmed by larger numbers of
      parasites.

PMID- 11318590
TI  - Dioctophymatid nematode larva found from human skin with creeping eruption.
AB  - A female dioctophymatid nematode larva, presumably belonging to the genus
      Dioctophyme, was found in a dermal granuloma accompanied by creeping eruption in
      the left inner thigh of a 26-yr-old Chinese woman who had stayed in Japan for 4
      yr. Morphology of the sectioned worm is described in detail. This is the fourth
      case of dermal infection with dioctophymatid larva in humans.

PMID- 11318591
TI  - Telomeres, telomerase, and lupus: the long and short of it.

PMID- 11318592
TI  - Fc(epsilon)Ri-dependent signaling pathways in human mast cells.

PMID- 11318593
TI  - Telomere shortening and decreased replicative potential, contrasted by continued
      proliferation of telomerase-positive CD8+CD28(lo) T cells in patients with
      systemic lupus erythematosus.
AB  - To evaluate whether the immune system of systemic lupus erythematosus (SLE)
      patients shows features of premature aging, we compared telomere length and
      proliferative potential of SLE peripheral blood mononuclear cells (PBMC) (N = 90)
      to those of controls (N = 64). SLE samples showed accelerated loss of telomeric
      DNA (P = 0.00008) and higher levels of senescent (< or =5 kb) telomeric DNA (P =
      0.00003). Viability cell counts and CFSE tracking in 6-week-old cell cultures
      indicated that SLE PBMC (CD8+ and CD4+ T cells) underwent fewer mitotic cycles
      and had shorter telomeres than controls (P = 0.04). However, a CD8(+)CD28(lo) T
      cell subset expanded preferentially in SLE-derived bulk cultures (P = 0.0009),
      preserved telomeric DNA (P = 0.01 vs entire CD8+), and displayed telomerase
      activity [2.1 telomerase arbitrary units (TAU) vs 0.5 TAU in CD8+CD28(hi) cells
      and 0.3 TAU in bulk PBMC; P = 0.05]. These T cell anomalies could be due to
      chronic in vivo stimulation of the immune system and may contribute to the immune
      dysregulation found in SLE.

PMID- 11318594
TI  - Soluble gC1q-R/p33, a cell protein that binds to the globular "heads" of C1q,
      effectively inhibits the growth of HIV-1 strains in cell cultures.
AB  - C1q and the outer envelope protein of HIV, gp120, have several structural and
      functional similarities. Therefore, it is plausible to assume that proteins that
      are able to interact with C1q may also interact with isolated gp120 as well as
      the whole HIV-1 virus. Based on this hypothesis, we studied the potential ability
      of the recombinant form of the 33-kDa protein, which binds to the globular
      "heads" of C1q (gC1q-R/p33), to inhibit the growth of different HIV-1 strains in
      cell cultures. gC1q-R/p33 was found to effectively and dose-dependently inhibit
      the production of one T-lymphotropic (X4) and one macrophage-tropic (R5) strain
      in human T cell lines (MT-4 and H9) and human monocyte-derived macrophage
      cultures, respectively. At a concentration range of 5-25 microg/ml, gC1q-R caused
      a marked and prolonged suppression of virus production. The extent of inhibition
      was enhanced when gC1q-R was first incubated with and then removed from the
      target cell cultures before virus infection, compared to that when the cells were
      infected with gC1q-R-HIV mixtures. The extent of inhibition was comparable to
      that of the Leu3a anti-CD4 antibody. Addition of gC1q-R to the cell cultures on
      day 1 or 2 after infection induced markedly less inhibition of HIV-1 growth than
      pretreatment of the cells just before or together with the infective HIV strains.
      In ELISA experiments, gC1q-R did not bind to a solid-phase recombinant gp120
      while strong and dose-dependent binding of gC1q-R to solid-phase CD4 was
      observed. Our present findings indicate that gC1q-R is an effective inhibitor of
      HIV-1 infection, which prevents viral entry by blocking the interaction between
      CD4 and gp120. Since gC1q-R is a human protein, it is most probably not antigenic
      in humans. It would seem logical, therefore, to consider gC1q-R or its fragments
      involved in the CD4 binding as potential therapeutic agents.

PMID- 11318595
TI  - ELISPOT analysis of hepatitis C virus protein-specific IFN-gamma-producing
      peripheral blood lymphocytes in infected humans with and without cirrhosis.
AB  - An improved ability to monitor hepatitis C virus (HCV)-specific T cell immunity
      in infected patients may provide novel information regarding the pathogenesis and
      prognosis of this infection. We used an ELISPOT assay to analyze a cross-section
      of HCV-infected humans. HCV-infected patients without cirrhosis, those with
      cirrhosis, and controls with other liver diseases were tested for recall
      responses to HCV Core and NS3 proteins. Peripheral blood lymphocytes (PBLs) from
      HCV-infected patients without cirrhosis responded to NS3 and Core proteins,
      producing predominantly IFN-gamma, with little IL-4 or IL-5. In contrast, PBLs
      from HCV-infected patients with cirrhosis responded to NS3, but not to the Core
      protein, suggesting a selectively altered immune state during cirrhosis. Our data
      provide support for the notion that HCV-specific IFN-gamma-producing immunity is
      important in the pathogenesis of progressing HCV-related disease.

PMID- 11318596
TI  - Vaccination with glutamic acid decarboxylase plasmid DNA protects mice from
      spontaneous autoimmune diabetes and B7/CD28 costimulation circumvents that
      protection.
AB  - The nonobese diabetic (NOD) mouse develops spontaneous T-cell-dependent
      autoimmune diabetes. We tested here whether vaccination of NOD mice with a
      plasmid DNA encoding glutamic acid decarboxylase (GAD), an initial target islet
      antigen of autoimmune T cell repertoire, would modulate their diabetes. Our
      results showed that vaccination of young or old female NOD mice with the GAD
      plasmid DNA, but not control-plasmid DNA, effectively prevented their diabetes,
      demonstrating that GAD-plasmid DNA vaccination is quite effective in abrogating
      diabetes even after the development of insulitis. The prevention of diabetes did
      not follow the induction of immunoregulatory Th2 cells but was dependent upon
      CD28/B7 costimulation. Our results suggest a potential for treating spontaneous
      autoimmune diabetes via DNA vaccination with plasmids encoding self-Ag.

PMID- 11318597
TI  - Cell surface CD28 levels define four CD4+ T cell subsets: abnormal expression in
      rheumatoid arthritis.
AB  - CD28 is a costimulatory receptor expressed in most CD4(+) T cells. Despite the
      long-standing evidence for up- and downregulation of surface CD28 expression in
      vitro, and the key regulatory role assigned to the upregulation of CD28
      counterreceptor [the CD152 (CTLA-4) molecule], in vivo CD28 induction has
      attracted little attention. We studied CD28 and CD152 expression and function in
      33 rheumatoid arthritis (RA) patients, 20 clinically active and 13 inactive, and
      in 24 healthy donors. Four subsets of CD28(-), CD28(low), CD28(int), and
      CD28(high) peripheral blood human CD4(+) T cells were defined using three-color
      flow cytometry. The three CD28(+) subsets displayed a one-, two-, or threefold
      quantitative difference in their relative number of CD28 antibody binding sites,
      respectively (P < 0.01). RA patients, whether active or inactive, showed a
      distinct phenotype when compared to healthy donors: (i) the percentage of
      CD4(+)CD28(high) cells was increased twofold and the CD4(+)CD28(low) subset was
      reduced twofold (P < 0.01) and (ii) the CD4(+)CD28(high) cells from RA patients
      showed an in vivo activated phenotype, CD45RO(+)CD5(high)IL-2Ralpha(+) (P <
      0.01). Active RA patients were different from inactive patients. They showed a
      twofold increase in mean CD28 expression (P < 0.05), whereas each of the CD28(+)
      subsets in the inactive RA patients showed reduced expression when compared to
      healthy donors. Notably, both active and inactive RA patients showed abnormal
      CD28 upregulation when T cells were activated in vitro with CD3 antibodies, but
      only inactive RA patients showed a hypoproliferative response to TCR/CD3
      triggering when compared to healthy donors (P < 0.01). This defective
      proliferation was normalized by concurrent crosslinking with CD28 antibody. No
      differences were noted in the expression of CD152 or CD80, a CD28 and CD152
      shared ligand. The disregulated in vivo expression of CD28 was related to the RA
      patients' disease activity and suggests that modulation of CD28 surface levels
      may be an additional mechanism to finely tune the delicate
      responsiveness/tolerance balance.

PMID- 11318598
TI  - Defective apoptosis in lymphocytes and the role of IL-2 in autoimmune hematologic
      cytopenias.
AB  - Fas-mediated signaling is important for lymphocyte elimination. We investigated
      lymphocytes for Fas-signaling defects in 20 pediatric patients with chronic
      hematologic autoimmunity. In 5 of 20 (25%), there was profound resistance to
      exogenous FasL-mediated lysis, Fas mAb, and anti-CD3. FasL function, though
      variable, was not significantly different from that of simultaneously evaluated
      controls. Only 1 patient had a Fas mutation and manifestations of autoimmune
      lymphoproliferative syndrome. In contrast, lymphocytes from his clinically normal
      mother with the same mutation were normally sensitive to FasL. In 3 patients,
      normal Fas-mediated lysis was restored with rhIL-2. IL-2 had no effect in the
      other 2 patients. Activation and proliferation functions of IL-2 were normal in
      all 5. We conclude that altered Fas signaling, independent of Fas mutations, can
      precipitate hematologic autoimmunity. IL-2 can rescue some lymphocytes from this
      defect. In IL-2 refractory cases, a persistently defective response to IL-2
      continues to confer a lymphocyte survival advantage. Hence, altered Fas pathway
      signaling with or without defective IL-2 responses should be considered in the
      etiology of hematologic autoimmunity.

PMID- 11318599
TI  - Mutational analysis of immunoglobulin germline derived Vlambda4A light chains in
      rheumatoid arthritis.
AB  - In order to better characterize the expression of a family of light chains
      previously expressed in IgM rheumatoid factors, we studied the usage and somatic
      mutational pattern of the Vlambda4A light chain gene in rheumatoid arthritis (RA)
      patients. We sequenced 11 different transcripts of Vlambda4A from the synovial
      tissue of three different RA patients. For comparison, we found 8 rearranged
      transcripts of Vlambda4A from 4 normal peripheral blood lymphocyte libraries and
      1 rearranged transcript from a non-RA con-A-resistant hybridoma in GenBank. A
      previously undescribed polymorphism of Vlambda4A was noted. Furthermore,
      conserved replacement mutations in the complementary determining regions, common
      silent mutations around these replacement mutations, and two subsets of mutated
      sequences were detected in multiple RA patients. These mutation patterns also
      correlated with observed consistencies in the rearrangements of the
      Vlambda4A/Jlambda junction. These data suggest that there is clonal expansion of
      Vlambda4A light chains in the RA synovium in response to a RA-specific antigen or
      as the result of an idiotypic response in RA.

PMID- 11318600
TI  - Mutational analysis of immunoglobulin germline derived Vlambda4B light chains in
      rheumatoid arthritis.
AB  - OBJECTIVE: We investigated the somatic mutational pattern of a specific Vlambda
      light chain variable region (V) gene in rheumatoid arthritis (RA) patients. The
      Vlambda4B light chain was chosen because of its location on the lambda locus and
      because of its previously observed use in IgM rheumatoid factors. METHODS: We
      sequenced 13 different mRNA transcripts of Vlambda4B from the synovium of three
      different RA patients. These were compared to 31 identifiable Vlambda4B sequences
      from GenBank, which were obtained from the PBL of patients without RA. RESULTS: A
      subset of Vlambda4B had a high rate of mutation, especially in the framework
      regions within the RA synovium. Furthermore, a set of codons within the first
      complementary determining region of Vlambda4B displayed frequent replacement
      mutations but did not possess any silent mutations. CONCLUSION: The hypermutation
      of RA synovial-derived Vlambda4B sequences, especially in the framework areas,
      may contribute to or may be the result of altered mutational mechanisms and/or
      prolonged B cell life.

PMID- 11318601
TI  - Autoantibody to DNA excision repair enzyme hMYH in a patient with rheumatic
      disease.
AB  - We screened a human HepG2 cell cDNA expression library using serum from a patient
      with rheumatic disease. This serum had immunofluorescence reactivity to nuclei
      with a homogeneous staining pattern and to punctuate nuclear aggregates,
      chromosomal metaphase plate, midbody, and cytoplasmic bridge. YT1, the longest
      cDNA clone isolated, has sequence identity to hMYH, the human homologue of the
      Escherichia coli excision repair enzyme, DNA adenine glycosylase MutY. YT1 is a
      truncated cDNA of 1619 bp, encoding amino acids 22-535, and contains a full
      length 3'-UTR sequence. We were unable to express a bacterial malE fusion protein
      incorporating amino acids 22 to 535 of hMYH. Consequently, we generated two
      additional malE fusion proteins of hMYH encoding amino acids 1-120 (pMAL
      c2:hMYH(1-120)) and amino acids 121-535 (pMAL-c2:hMYH(121-535)). The patient
      serum immunoblotted only pMAL-c2:hMYH(1-120), suggesting that the autoepitope(s)
      is restricted to amino acids 22-120 of hMYH, and detected a protein of
      approximately 59-kDa in total HeLa and nuclear extracts consistent with
      reactivity to hMYH. Affinity-purified autoantibodies to pMAL-c2:hMYH(1-120)
      reacted by immunoblot to pMAL-c2:hMYH(1-120), with no reactivity to pMAL
      c2:hMYH(121-535). By immunofluorescence, these antibodies displayed staining of
      nuclei. This is the first report of autoantibodies to hMYH in a patient with
      rheumatic disease. We were able to identify hMYH reactivity in relatively small
      cohorts of sera collected from rheumatoid factor-positive patients (6 of 18) and
      dsDNA-positive patients (1 of 18), with no reactivity detected in serum collected
      from 9 healthy subjects.

PMID- 11318602
TI  - Idiopathic CD4+ T cell lymphocytopenia evolving to monoclonal immunoglobulins and
      progressive renal damage responsive to IL-2 therapy.
AB  - Idiopathic CD4+ T cell lymphocytopenia was unexpectedly detected in a 33-year
      old, otherwise healthy young woman with no HIV or other viral infection,
      autoimmune, or neoplastic disease or increased susceptibility to infection. CD4+
      T cell levels were 60-140/microl over a 3.5-year period. Following an uneventful
      pregnancy, the patient developed anemia and interstitial nephritis associated
      with a plasma cell dyscrasia with a monoclonal IgA gammopathy and a shifting
      immunoglobulin pattern that included IgG and IgA monoclonal proteins and
      increased urinary light chains. Osteolytic lesions were never detected and bone
      marrow aspirations revealed up to 10% atypical plasma cells. Various therapies
      often used in treating multiple myeloma only temporarily controlled the
      increasing renal damage. IL-2 therapy of 600,000 to 1 million units
      subcutaneously daily resulted in increased CD4+ T cells to normal levels, a
      decrease in the gammopathy, a return of renal function, energy, and weight gain,
      and apparently normal health status sustained for 2 years. The findings are
      compatible with a potentially fatal but nonmalignant immunoregulatory disorder
      that can be controlled by IL-2 administration.

PMID- 11318603
TI  - Leiomodins: larger members of the tropomodulin (Tmod) gene family.
AB  - The 64-kDa autoantigen D1 or 1D, first identified as a potential autoantigen in
      Graves' disease, is similar to the tropomodulin (Tmod) family of actin filament
      pointed end-capping proteins. A novel gene with significant similarity to the 64
      kDa human autoantigen D1 has been cloned from both humans and mice, and the
      genomic sequences of both genes have been identified. These genes form a
      subfamily closely related to the Tmods and are here named the Leiomodins (Lmods).
      Both Lmod genes display a conserved intron-exon structure, as do three Tmod
      genes, but the intron-exon structure of the Lmods and the Tmods is divergent.
      mRNA expression analysis indicates that the gene formerly known as the 64-kDa
      autoantigen D1 is most highly expressed in a variety of human tissues that
      contain smooth muscle, earning it the name smooth muscle Leiomodin (SM-Lmod; HGMW
      approved symbol LMOD1). Transcripts encoding the novel Lmod gene are present
      exclusively in fetal and adult heart and adult skeletal muscle, and it is here
      named cardiac Leiomodin (C-Lmod; HGMW-approved symbol LMOD2). Human C-Lmod is
      located near the hypertrophic cardiomyopathy locus CMH6 on human chromosome 7q3,
      potentially implicating it in this disease. Our data demonstrate that the Lmods
      are evolutionarily related and display tissue-specific patterns of expression
      distinct from, but overlapping with, the expression of Tmod isoforms.

PMID- 11318604
TI  - Characterization of mammalian orthologues of the Drosophila osa gene: cDNA
      cloning, expression, chromosomal localization, and direct physical interaction
      with Brahma chromatin-remodeling complex.
AB  - The osa gene of Drosophila melanogaster encodes a nuclear protein that is a
      component of the Brahma chromatin-remodeling complex. Osa is required for
      embryonic segmentation, development of the notum and wing margin, and
      photoreceptor differentiation. In these tissues, osa mutations have effects
      opposite to those caused by wingless (wg) mutations, suggesting that osa
      functions as an antagonist of wg signaling. Here we describe the cloning and
      characterization of mammalian orthologues of osa. Three evolutionarily conserved
      domains were identified in Osa family members: the N-terminal Bright domain and C
      terminally located Osa homology domains 1 and 2. RNase protection analysis
      indicates a widespread expression of the Osa1 gene during mouse development, in
      adult tissues, and in cultured cell lines. The Osa1 gene was localized to mouse
      chromosome 4, within the region syntenic to chromosomal position 1p35-p36 of its
      human counterpart. We present evidence that the OSA1 product is localized in the
      nucleus and associates with human Brahma complex, which suggests evolutionarily
      conserved function for Osa in gene regulation between mammals and Drosophila.

PMID- 11318605
TI  - RET rearrangements in radiation-induced papillary thyroid carcinomas: high
      prevalence of topoisomerase I sites at breakpoints and microhomology-mediated end
      joining in ELE1 and RET chimeric genes.
AB  - Children exposed to radioactive iodine after the Chernobyl reactor accident
      frequently developed papillary thyroid carcinomas (PTC). The predominant
      molecular lesions in these tumors are rearrangements of the RET receptor tyrosine
      kinase gene. Various types of RET rearrangements have been described. More than
      90% of PTC with RET rearrangement exhibit a PTC1 or PTC3 type of rearrangement
      with an inversion of the H4 or ELE1 gene, respectively, on chromosome 10. To
      obtain closer insight into the mechanisms underlying PTC3 inversions, we analyzed
      the genomic breakpoints of 22 reciprocal and 4 nonreciprocal ELE1 and RET
      rearrangements in 26 post-Chernobyl tumor samples. In contrast to previous
      assumptions, an accumulation of breakpoints at the two Alu elements in the ELE1
      sequence was not observed. Instead, breakpoints are distributed in the affected
      introns of both genes without significant clustering. When compared to the
      corresponding wildtype sequences, the majority of breakpoints (92%) do not
      contain larger deletions or insertions. Most remarkably, at least one
      topoisomerase I site was found exactly at or in close vicinity to all
      breakpoints, indicating a potential role for this enzyme in the formation of DNA
      strand breaks and/or ELE1 and RET inversions. The presence of short regions of
      sequence homology (microhomologies) and short direct and inverted repeats at the
      majority of breakpoints furthermore indicates a nonhomologous DNA end-joining
      mechanism in the formation of chimeric ELE1/Ret and Ret/ELE1 genes.

PMID- 11318606
TI  - Expression and replication timing patterns of wildtype and translocated BCL2
      genes.
AB  - Translocation of the BCL2 gene from chromosome 18 to chromosome 14 results in
      constitutive expression of the gene. We have recently demonstrated that the major
      breakpoint region (mbr) of BCL2, which is implicated in 70% of t(14;18)
      translocations present in human follicular lymphoma, is a matrix attachment
      region. Since these regions are implicated in control of both transcription and
      replication, we wished to determine whether BCL2 translocation was also
      accompanied by changes in replication timing of the translocated allele. Using
      both fluorescence in situ hybridization and allele-specific PCR, we have
      demonstrated that the translocated allele replicates at the G1/S boundary, while
      the wildtype allele continues to replicate as usual in mid-S phase. These
      differences are accompanied by allele-specific changes in BCL2 expression. Since
      the net structural effect of t(14;18) translocations within the mbr is to disrupt
      the BCL2 MAR and replace it with the IGH MARs located just downstream of each
      breakpoint, we conclude that MAR exchange is a significant, selectable outcome of
      these translocations. We propose that subsequent changes of replication and
      transcriptional patterns for the translocated BCL2 allele result from this
      exchange and represent important early steps in lymphomagenesis.

PMID- 11318607
TI  - 09/15: Comparative genomics of a conserved chromosomal region associated with a
      complex human phenotype.
AB  - Three genes that encode related immunoglobulin superfamily molecules have
      recently been mapped to human chromosome 15 in the region q22.3-q23 and to the
      syntenic region on mouse chromosome 9. These genes presumably derived from gene
      duplications, and they are highly similar to Deleted in Colorectal Cancer (DCC),
      which functions as an axon guidance molecule during development of the nervous
      system. To find out whether additional genes of this class were present in a
      chromosomal cluster, we produced a comparative physical map within the region of
      synteny between mouse chromosome 9 and human chromosome 15. This interval
      overlaps the critical region for the fourth genetic locus for Bardet-Biedl
      syndrome (BBS4) in humans. Bardet-Biedl syndrome (OMIM 600374) is characterized
      by poly/syn/brachydactyly, retinal degeneration, hypogonadism, mental
      retardation, obesity, diabetes, and kidney abnormalities. A detailed map of this
      locus will help to identify candidate genes for this disorder.

PMID- 11318608
TI  - Identification of differentially expressed nucleolar TGF-beta1 target (DENTT) in
      human lung cancer cells that is a new member of the TSPY/SET/NAP-1 superfamily.
AB  - The transforming growth factor-beta1 (TGF-beta1) responsive epithelial non-small
      cell lung cancer (NSCLC) cell line NCI-H727 was used to identify potential target
      genes involved in TGF-beta1-mediated responses. Comparative cDNA expression
      patterns between cells treated with TGF-beta1 and those treated with vehicle were
      generated by differential mRNA display. One 496-bp fragment, differentially
      increased threefold by TGF-beta1 and hybridizing to a 2.7-kb mRNA species in NCI
      H727 cells by Northern analysis, revealed no significant match to any known gene
      sequence. The mRNA transcript of this novel gene that we named differentially
      expressed nucleolar TGF-beta1 target (DENTT) is expressed in several normal human
      tissues, with the highest level of expression in brain. Human brain cDNA library
      screening and 5' rapid amplification of cDNA ends yielded full-length DENTT cDNA
      containing an 1899-bp open reading frame encoding a predicted 633-amino-acid
      protein with four potential nuclear localization signals (NLSs) and two coiled
      coil regions. DENTT contains a conserved 191-residue domain that shows
      significant identity to, and defines, the TSPY/TSPY-like/SET/NAP-1 superfamily.
      Enhanced green fluorescent protein (EGFP)-tagged full-length DENTT transfected
      into COS-7 cells showed nucleolar and cytoplasmic localization. Transfection of
      EGFP-tagged DENTT NLS deletion constructs lacking the bipartite NLS-1 were
      excluded from the nucleolus. While NLS-1 is necessary for nucleolar localization
      of DENTT, it is not sufficient for sole nucleolar localization. Our data show
      that DENTT mRNA induction by TGF-beta1 correlates with induction of TGF-beta1
      mRNA, induction of extracellular matrix gene expression, and inhibition of colony
      formation in soft agarose in TGF-beta1 responsive NSCLC cells when exposed to TGF
      beta1. TGF-beta1 does not induce DENTT mRNA expression in TGF-beta1 nonresponsive
      NSCLC cells. Our data suggest that this novel TGF-beta1 target gene has distinct
      domains for direction to different subnuclear locations.

PMID- 11318609
TI  - Transcripts of Fliz1, a nuclear zinc finger protein, are expressed in discrete
      foci of the murine fetal liver.
AB  - The origin and expansion of hematopoietic progenitor and stem cells during fetal
      development and their differentiation into mature effector cells are thought to
      be driven by the activation of developmental stage- and cell-lineage-specific
      genes. To gain further insight into the molecular mechanisms regulating the
      expansion and differentiation of fetal hematopoietic progenitor and stem cells,
      we performed differential display RT-PCR analysis on fractionated murine E12
      fetal liver cells. We identified a novel transcript predicted to encode a protein
      of 305 amino acids with a calculated molecular mass of 35 kDa, containing a
      charged domain and three putative C(3)H-type zinc fingers. The fetal liver zinc
      finger protein 1 (Fliz1) transcript is approximately 1.8 kb and is variably
      expressed both during embryogenesis and in adult tissues. Fliz1 expression was
      detected in discrete cell foci in the fetal liver and in LIN(-)/ckit(+) cells.
      Nuclear localization studies revealed that Fliz1 is targeted to the nucleus.
      Thus, Fliz1 is a newly identified nuclear protein expressed in hematopoietic
      progenitor cells of the developing fetal liver.

PMID- 11318610
TI  - A physical and transcript map of the MCOLN1 gene region on human chromosome
      19p13.3-p13.2.
AB  - Mutations in MCOLN1 have been found to cause mucolipidosis type IV (MLIV; MIM
      252650), a rare autosomal recessive lysosomal storage disorder found primarily in
      the Ashkenazi Jewish population. As a part of the successful cloning of MCOLN1,
      we constructed a 1.4-Mb physical map containing 14 BACs and 4 cosmids that
      encompasses the region surrounding MCOLN1 on human chromosome 19p13.3-p13.2-a
      region to which linkage or association has been reported for multiple diseases.
      Here we detail the precise physical mapping of 28 expressed sequence tags that
      represent unique UniGene clusters, of which 15 are known genes. We present a
      detailed transcript map of the MCOLN1 gene region that includes the genes
      KIAA0521, neuropathy target esterase (NTE), a novel zinc finger gene, and two
      novel transcripts in addition to MCOLN1. We also report the identification of
      eight new polymorphic markers between D19S406 and D19S912, which allowed us to
      pinpoint the location of MCOLN1 by haplotype analysis and which will facilitate
      future fine-mapping in this region. Additionally, we briefly describe the
      correlation between the observed haplotypes and the mutations found in MCOLN1.
      The complete 14-marker haplotypes of non-Jewish disease chromosomes, which are
      crucial for the genetic diagnosis of MLIV in the non-Jewish population, are
      presented here for the first time.

PMID- 11318611
TI  - Cloning and characterization of 13 novel transcripts and the human RGS8 gene from
      the 1q25 region encompassing the hereditary prostate cancer (HPC1) locus.
AB  - The aim of this study was to develop a saturated transcript map of the region
      encompassing the HPC1 locus to identify the susceptibility genes involved in
      hereditary prostate cancer (OMIM 176807) and hyperparathyroidism-jaw tumor
      syndrome (OMIM 145001). We previously reported the generation of a 6-Mb BAC/PAC
      contig of the candidate region and employed various strategies, such as database
      searching, exon-trapping, direct cDNA hybridization, and sample sequencing of
      BACs, to identify all potential transcripts. These efforts led to the
      identification and precise localization on the BAC contig of 59 transcripts
      representing 22 known genes and 37 potential transcripts represented by ESTs and
      exon traps. Here we report the detailed characterization of these ESTs into full
      length transcript sequences, their expression pattern in various tissues, their
      genomic organization, and their homology to known genes. We have also identified
      an Alu insertion polymorphism in the intron of one of the transcripts. Overall,
      data on 13 novel transcripts and the human RGS8 gene (homologue of the rat RGS8
      gene) are presented in this paper. Ten of the 13 novel transcripts are expressed
      in prostate tissue and represent positional candidates for HPC1.

PMID- 11318612
TI  - Genetic, physical, and transcript map of the Ltxs1 region of mouse chromosome 11.
AB  - Lethal factor (LF) is a toxin secreted by Bacillus anthracis that plays an
      important role in the pathogenesis of anthrax. Intoxication with LF results in a
      macrophage-specific cytolysis that is not well understood. Interestingly, inbred
      mouse strains exhibit dramatic differences in the susceptibility of their
      cultured macrophages to killing by LF, and a gene that influences this phenotype,
      called Ltxs1, has been mapped to mouse chromosome 11. Here we report a high
      resolution genetic map that confines the Ltxs1 region to a 0.51-cM interval
      between D11Mit90 and D11Die37/D11Die38. We have also constructed a complete
      physical map of YAC and BAC clones covering the Ltxs1 region. In conjunction with
      synteny homology searching, BLAST searches of sequences obtained from the clones
      in the physical map have revealed 14 known genes and five ESTs that reside in the
      critical interval. Additionally, a region of 100 kb or more is deleted in the
      Ltxs1 interval of some strains. Our genetic, physical, and transcript map
      provides an important resource for the molecular cloning of Ltxs1.

PMID- 11318613
TI  - A retrotransposon-derived gene, PEG10, is a novel imprinted gene located on human
      chromosome 7q21.
AB  - A novel paternally expressed imprinted gene, PEG10 (Paternally Expressed 10), was
      identified on human chromosome 7q21. PEG10 is located near the SGCE (Sarcoglycan
      epsilon) gene, whose mouse homologue was recently shown to be imprinted.
      Therefore, it is highly possible that a new imprinted gene cluster exists on
      human chromosome 7q21. Analysis of two predicted open reading frames (ORF1 and
      ORF2) revealed that ORF1 and ORF2 have homology to the gag and pol proteins of
      some vertebrate retrotransposons, respectively. These data suggest that PEG10 is
      derived from a retrotransposon that was previously integrated into the mammalian
      genome. PEG10 is likely to be essential for understanding how exogenous genes
      become imprinted.

PMID- 11318616
TI  - Formal theory of spin--lattice relaxation.

PMID- 11318614
TI  - Human ITCH is a coregulator of the hematopoietic transcription factor NF-E2.
AB  - We have cloned a new protein that interacts with the hematopoietic DNA-binding
      transcription factor, p45/NF-E2, by screening a human erythroleukemia cell cDNA
      library with the yeast two-hybrid approach. Predicted peptide sequence and
      chromosomal mapping identified the cloned molecule to be the product of the human
      ortholog of the mouse Itch gene, which has been implicated previously in the
      regulation of growth and differentiation of erythroid and lymphoid cells.
      Transfection experiments indicate that this human ITCH protein can act as a
      transcriptional corepressor of p45/NF-E2. Our data provide novel insights into
      the functional roles of the mammalian ITCH proteins in the development of
      hematopoietic cell lineages.

PMID- 11318617
TI  - Revision of spin echoes in pure nuclear quadrupole resonance.
AB  - Goldman's spin-1/2 formalism has been used for describing the response of an
      I=3/2 spin system to a two-pulse sequence in a pure nuclear quadrupole resonance
      experiment. A detailed analysis of the polarization evolution and quadrupolar
      echo generation is carried out through the use of explicit expressions for
      secular homo- and heteronuclear dipolar interactions. In striking contrast with
      previous studies, it is predicted that Van Vleck's second moments governing a
      classical solid-echo or Hahn sequence differ from those obtained by equivalent
      means in magnetic resonance. In fact, it is shown that, although measured moments
      still complement each other, the combined use of standard sequences does not
      allow the separate determination of homo- and heteronuclear dipolar contributions
      to the linewidth, not even in an indirect manner. In this context, the importance
      and potential usefulness of a crossed coil probe are also briefly discussed.

PMID- 11318618
TI  - A Q-band pulse EPR/ENDOR spectrometer and the implementation of advanced one- and
      two-dimensional pulse EPR methodology.
AB  - A versatile high-power pulse Q-band EPR spectrometer operating at 34.5--35.5 GHz
      and in a temperature range of 4--300 K is described. The spectrometer allows one
      to perform one- and two-dimensional multifrequency pulse EPR and pulse ENDOR
      experiments, as well as continuous wave experiments. It is equipped with two
      microwave sources and four microwave channels to generate pulse sequences with
      different amplitudes, phases, and carrier frequencies. A microwave pulse power of
      up to 100 W is available. Two channels form radiofrequency pulses with adjustable
      phases for ENDOR experiments. The spectrometer performance is demonstrated by
      single crystal pulse ENDOR experiments on a copper complex. A HYSCORE experiment
      demonstrates that the advantages of high-field EPR and correlation spectroscopy
      can be combined and exploited at Q-band. Furthermore, we illustrate how this
      combination can be used in cases where the HYSCORE experiment is no longer
      effective at 35 GHz because of the shallow modulation depth. Even in cases where
      the echo modulation is virtually absent in the HYSCORE experiment at Q-band,
      matched microwave pulses allow one to get HYSCORE spectra with a signal-to-noise
      ratio as good as at X-band. Finally, it is shown that the high microwave power,
      the short pulses, and the broad resonator bandwidth make the spectrometer well
      suited to Fourier transform EPR experiments.

PMID- 11318619
TI  - Determination of the rotational diffusion tensor of macromolecules in solution
      from nmr relaxation data with a combination of exact and approximate methods-
      application to the determination of interdomain orientation in multidomain
      proteins.
AB  - In this paper we present a method for determining the rotational diffusion tensor
      from NMR relaxation data using a combination of approximate and exact methods.
      The approximate method, which is computationally less intensive, computes values
      of the principal components of the diffusion tensor and estimates the Euler
      angles, which relate the principal axis frame of the diffusion tensor to the
      molecular frame. The approximate values of the principal components are then used
      as starting points for an exact calculation by a downhill simplex search for the
      principal components of the tensor over a grid of the space of Euler angles
      relating the diffusion tensor frame to the molecular frame. The search space of
      Euler angles is restricted using the tensor orientations calculated using the
      approximate method. The utility of this approach is demonstrated using both
      simulated and experimental relaxation data. A quality factor that determines the
      extent of the agreement between the measured and predicted relaxation data is
      provided. This approach is then used to estimate the relative orientation of SH3
      and SH2 domains in the SH(32) dual-domain construct of Abelson kinase complexed
      with a consolidated ligand.

PMID- 11318620
TI  - Development of a resonator with automatic tuning and coupling capability to
      minimize sample motion noise for in vivo EPR spectroscopy.
AB  - EPR spectroscopy has been applied to measure free radicals in vivo; however,
      respiratory, cardiac, and other movements of living animals are a major source of
      noise and spectral distortion. Sample motions result in changes in resonator
      frequency, Q, and coupling. These instabilities limit the applications that can
      be performed and the quality of data that can be obtained. Therefore, it is of
      great importance to develop resonators with automatic tuning and automatic
      coupling capability. We report the development of automatic tuning and automatic
      coupling provisions for a 750-MHz transversely oriented electric field reentrant
      resonator using two electronically tunable high Q hyperabrupt varactor diodes and
      feedback loops. In both moving phantoms and living mice, these automatic coupling
      control and automatic tuning control provisions resulted in an 8- to 10-fold
      increase in signal-to-noise ratio.

PMID- 11318621
TI  - Determination of genuine diffusivities in heterogeneous media using stimulated
      echo pulsed field gradient NMR.
AB  - Pulsed field gradient (PFG) NMR diffusion measurements in heterogeneous media may
      lead to erroneous results due to the disturbing influence of internal magnetic
      field gradients. Here, we present a simple theoretical model which allows one to
      interpret data obtained by stimulated spin echo PFG NMR in the presence of
      spatially varying internal field gradients. Using the results of this theory, the
      genuine self-diffusion coefficients in heterogeneous media may be extrapolated
      from the dependence of the apparent diffusivities on the dephasing time of the
      simulated echo PFG NMR sequence. Experimental evidence that such extrapolation
      yields satisfactory results for self-diffusion of hexadecane in natural sediments
      (sand) and of n-octanol in doped MgO pastes is provided.

PMID- 11318622
TI  - Delayed-focus pulses optimized using simulated annealing.
AB  - Unlike prefocused pulses and shaped pulses based on the linear response theory,
      delayed-focus pulses (X.-L. Wu et al., 1991, Magn. Reson. Med. 20, 165--170)
      produce a selective spin echo after a predefined short delay without using a pi
      refocusing pulse. In this paper, a series of delayed-focus pulses of different
      flip angles are proposed based on optimization using Fourier series
      representation and simulated annealing. The resistance of these delayed-focus
      pulses to T(2) relaxation is also demonstrated using numerical simulation of
      Bloch equations.

PMID- 11318623
TI  - The VMD-XPLOR visualization package for NMR structure refinement.
AB  - In this paper we present the VMD-XPLOR package combining the XPLOR refinement
      program and the VMD visualization program and including extensions for use in the
      determination of biomolecular structures from NMR data. The package allows one to
      pass structures to and to control VMD from the XPLOR scripting level. The VMD
      graphical interface has been customized for NMR structure refinement, including
      support to manipulate coordinates interactively while graphically visualizing NMR
      experimental information in the context of a molecular structure. Finally, the
      VMD-XPLOR interface is modular so that it is readily transferable to other
      refinement programs (such as CNS).

PMID- 11318624
TI  - Quantitation of localized (31)P magnetic resonance spectra based on the
      reciprocity principle.
AB  - There is a need for absolute quantitation methods in (31)P magnetic resonance
      spectroscopy, because none of the phosphorous-containing metabolites is
      necessarily constant in pathology. Here, a method for absolute quantitation of in
      vivo (31)P MR spectra that provides reproducible metabolite contents in
      institutional or standard units is described. It relies on the reciprocity
      principle, i.e., the proportionality between the B(1) field map and the map of
      reception strength for a coil with identical relative current distributions in
      receive and transmit mode. Cerebral tissue contents of (31)P metabolites were
      determined in a predominantly white matter-containing location in healthy
      subjects. The results are in good agreement with the literature and the
      interexamination coefficient of variance is better than that in most previous
      studies. A gender difference found for some of the (31)P metabolites may be
      explained by different voxel composition.

PMID- 11318625
TI  - Pitfalls in the measurement of metabolite concentrations using the one-pulse
      experiment in in Vivo NMR: commentary on "On neglecting chemical exchange effects
      when correcting in vivo (31)P MRS data for partial saturation".
AB  - In an article in a previous issue of the Journal of Magnetic Resonance, Ouwerkerk
      and Bottomley (J. Magn. Reson. 148, pp. 425--435, 2001) show that even in the
      presence of chemical exchange, the dependence of saturation factors on repetition
      time in the one-pulse experiment is approximately monoexponential. They conclude
      from this fact that the effect of chemical exchange on the use of saturation
      factors when correcting for partial saturation is negligible. We take issue with
      this conclusion and demonstrate that because saturation factors in the presence
      of chemical exchange are strongly dependent upon all of the chemical parameters
      of the system, that is, upon all T(1)'s and M(0)'s of resonances in the exchange
      network and upon the reaction rates themselves, it is problematic to apply
      saturation factor corrections in situations in which any of these parameters may
      change. The error criterion we establish reflects actual errors in quantitation,
      rather than departures from monoexponentiality.

PMID- 11318626
TI  - Double-quantum-filtered NMR signals in inhomogeneous magnetic fields.
AB  - The possibility of exciting and detecting proton NMR double-quantum coherences in
      inhomogeneous static and radiofrequency magnetic fields was investigated. For
      this purpose specialized pulse sequences which partially refocus the strongly
      inhomogeneous evolution of the spin system and generate double-quantum buildup
      and decay curves were implemented on the NMR MOUSE (mobile universal surface
      explorer). The theoretical justification of the method was developed for the
      simple two-spin-1/2 system. The performances of the same pulse sequences were
      also tested on a solid-state high-field NMR spectrometer. It was shown that DQ
      decay curves have a better signal-to-noise ratio in the initial time regime than
      DQ buildup curves. The double-quantum buildup and decay curves were recorded for
      a series of cross-linked natural rubber samples. These curves give access to
      quantitative values of the ratio of proton total residual dipolar couplings which
      are in good agreement with those measured in homogeneous fields. A linear
      dependence of these ratios on the sulfur-accelerator content was found.

PMID- 11318627
TI  - Ramped-speed cross polarization MAS NMR.
AB  - The inverse cubic dependency of the acceleration of a rotor on its diameter
      allows for mechanical dynamics comparable to spin dynamics in coupled spin
      systems. Rotor acceleration up to 300 kHz/s was measured. This feature can be
      used to simplify existing experiments and explore entirely new ones in the study
      of spin topologies and material properties.

PMID- 11318628
TI  - High-resolution NMR of quadrupolar nuclei using mixed multiple-quantum
      coherences.
AB  - A multiple-quantum magic angle spinning (MQMAS) NMR experiment of quadrupolar
      nuclei is demonstrated, which uses two different multiple quantum coherences in
      t(1) to refocus the quadrupolar broadening. This experiment has the potential of
      achieving improved resolution over current techniques.

PMID- 11318629
TI  - A maximum likelihood method for determining D(a)(PQ) and R for sets of dipolar
      coupling data.
AB  - The algorithms available today that use dipolar coupling data for macromolecular
      structure determination require the independent determination of two parameters,
      D(a)(PQ) and R. Methods exist for obtaining these parameters when the set of
      dipolar couplings available is large and the orientations of the interatomic
      vectors on which they report is isotropically distributed. These methods are less
      satisfactory when the set is small and anisotropic. Described here is a maximum
      likelihood method that extracts accurate values for D(a)(PQ) and R from small,
      anisotropic data sets. Also demonstrated is a procedure for estimating the errors
      associated with the values of D(a)(PQ) and R obtained and for incorporating these
      errors into refinement protocols.

PMID- 11318630
TI  - Measurement of homonuclear proton couplings from regular 2D COSY spectra.
AB  - An interactive computer procedure is described which determines (1)H--(1)H
      couplings from fitting the cross-peak multiplets in regular phase-sensitive COSY
      spectra. The robustness and simplicity of the method rely on the fact that a
      given cross-peak intensity is not an independent variable in the fitting
      procedure, making it possible to measure couplings accurately even from
      individual cross peaks with unresolved multiplet structure.

PMID- 11318631
TI  - On neglecting chemical exchange when correcting in vivo (31)P MRS data for
      partial saturation: commentary on: "Pitfalls in the measurement of metabolite
      concentrations using the one-pulse experiment in in Vivo NMR".
AB  - This article replies to Spencer et al. (J. Magn. Reson. 149, 251--257, 2001)
      concerning the degree to which chemical exchange affects partial saturation
      corrections using saturation factors. Considering the important case of in vivo
      (31)P NMR, we employ differential analysis to demonstrate a broad range of
      experimental conditions over which chemical exchange minimally affects saturation
      factors, and near-optimum signal-to-noise ratio is preserved. The analysis
      contradicts Spencer et al.'s broad claim that chemical exchange results in a
      strong dependence of saturation factors upon M(0)'s and T(1) and exchange
      parameters. For Spencer et al.'s example of a dynamic (31)P NMR experiment in
      which phosphocreatine varies 20-fold, we show that our strategy of measuring
      saturation factors at the start and end of the study reduces errors in saturation
      corrections to 2% for the high-energy phosphates.

PMID- 11318632
TI  - Conformationally specific misfolding of an integral membrane protein.
AB  - Membrane protein misfolding is related to the etiology of many diseases, but is
      poorly understood, particularly from a structural standpoint. This study focuses
      upon misfolding of a mutant form of diacylglycerol kinase (s-DAGK), a 40 kDa
      homotrimeric protein having nine transmembrane segments. Preparations of s-DAGK
      sometimes contain a kinetically trapped misfolded population, as evidenced by
      lower-than-expected enzyme activity (with no accompanying change in substrate
      K(m)) and by the appearance of a second band in electrophoresis gels. Misfolding
      of s-DAGK may take place during cellular overexpression, but can also be
      reproduced using the purified enzyme. TROSY NMR spectra of s-DAGK as a 100 kDa
      complex with detergent micelles exhibit a single additional set of resonances
      from the misfolded form, indicating a single misfolded conformational state. The
      relative intensities of these extra resonances correlate with the percent
      reduction in enzyme activity below the maximum observed for fully folded s-DAGK.
      Misfolded s-DAGK exhibits a modest difference in its far-UV CD spectrum compared
      to the folded enzyme, consistent with a small degree of variance in secondary
      structural content between the two forms. However, differences in NMR chemical
      shift dispersion and temperature-dependent line widths exhibited by folded and
      misfolded s-DAGK support the notion that they represent very different structural
      states. Cross-linking experiments indicate that both the correctly folded enzyme
      and the kinetically trapped misfolded form are homotrimers. This work appears to
      represent the first documentation of conformationally specific misfolding of an
      integral membrane protein.

PMID- 11318633
TI  - Mycobacterium tuberculosis mycothione reductase: pH dependence of the kinetic
      parameters and kinetic isotope effects.
AB  - The recent identification of the enzyme in Mycobacterium tuberculosis that
      catalyzes the NADPH-dependent reduction of the unique low molecular weight
      disulfide mycothione, mycothione reductase, has led us to examine the mechanism
      of catalysis in greater detail. The pH dependence of the kinetic parameters V and
      V/K for NADPH, NADH, and an active analogue of mycothione disulfide, des-myo
      inositol mycothione disulfide, has been determined. An analysis of the pH
      profiles has allowed the tentative assignment of catalytically significant
      residues crucial to the mechanism of disulfide reduction, namely, the His444
      Glu449 ion pair and Cys39. Solvent kinetic isotope effects were observed on V and
      V/K(DIMSSM), yielding values of 1.7 +/- 0.2 and 1.4 +/- 0.2, respectively, but
      not on V/K(NADPH). Proton inventory studies (V versus mole fraction of D(2)O)
      were linear, indicative of a single proton transfer in a solvent isotopically
      sensitive step. Steady-state primary deuterium kinetic isotope effects on V have
      been determined using NADPH and NADH, yielding values of 1.27 +/- 0.03 and 1.66
      +/- 0.14, respectively. The pre-steady-state primary deuterium kinetic isotope
      effect on enzyme reduction has values of 1.82 +/- 0.04 and 1.59 +/- 0.06 for
      NADPH and NADH, respectively. The steady-state primary deuterium kinetic isotope
      effect using NADH coincide with that obtained under single turnover conditions,
      suggesting the complete expression of the intrinsic primary kinetic isotope
      effect. Rapid reaction studies on the reductive half-reaction using NADPH and
      NADH yielded maximal rates of 129 +/- 2 and 20 +/- 1 s(-1), respectively, while
      similar studies of the oxidation of the two-electron reduced enzyme by mycothiol
      disulfide yielded a maximum rate of 190 +/- 10 s(-1). These data suggest a unique
      flavoprotein disulfide mechanism in which the rate of the oxidative half-reaction
      is slightly faster than the rate of the reductive half-reaction.

PMID- 11318634
TI  - Structures of apomyoglobin's various acid-destabilized forms.
AB  - The structures and the cold and hot melting thermodynamics of the acid- and salt
      destabilized states of horse heart apomyoglobin (apoMb), including the E
      (extended) and various I forms, are studied using probes of tertiary structure
      (tryptophan fluorescence and FTIR spectroscopy) and secondary structure (far-UV
      CD and FTIR spectroscopy). These forms likely resemble early structures in the
      folding of the largely helical protein. Both the I and E forms retain the AGH
      core whereby the two ends of the protein are tied together with sufficient
      numbers of tertiary contacts, involving a number of hydrophobic residues, to show
      cooperative melting. The melting thermodynamics of E and I are distinctly
      different. E contains no other tertiary structure and probably little other
      secondary structure apart from the core. The more destabilized E form appears to
      contain "random" buried runs of polypeptide backbone which convert to alpha-helix
      in the I form(s). Most interestingly, E consists not of a single structure but is
      composed of a heterogeneous mixture of conformations, all showing corelike
      cooperative melting characteristics, and consisting presumably of varying
      contacts between the A portion of apomyoglobin and the G-H hairpin. These results
      bear on the energy landscape and structural features of the early part of
      apomyoglobin's folding pathway.

PMID- 11318635
TI  - Core formation in apomyoglobin: probing the upper reaches of the folding energy
      landscape.
AB  - An acid-destabilized form of apomyoglobin, the so-called E state, consists of a
      set of heterogeneous structures that are all characterized by a stable
      hydrophobic core composed of 30-40 residues at the intersection of the A, G, and
      H helices of the protein, with little other secondary structure and no other
      tertiary structure. Relaxation kinetics studies were carried out to characterize
      the dynamics of core melting and formation in this protein. The unfolding and/or
      refolding response is induced by a laser-induced temperature jump between the
      folded and unfolded forms of E, and structural changes are monitored using the
      infrared amide I' absorbance at 1648-1651 cm(-1) that reports on the formation of
      solvent-protected, native-like helix in the core and by fluorescence emission
      changes from apomyoglobin's Trp14, a measure of burial of the indole group of
      this residue. The fluorescence kinetics data are monoexponential with a
      relaxation time of 14 micros. However, infrared kinetics data are best fit to a
      biexponential function with relaxation times of 14 and 59 micros. These
      relaxation times are very fast, close to the limits placed on folding reactions
      by diffusion. The 14 micros relaxation time is weakly temperature dependent and
      thus represents a pathway that is energetically downhill. The appearance of this
      relaxation time in both the fluorescence and infrared measurements indicates that
      this folding event proceeds by a concomitant formation of compact secondary and
      tertiary structures. The 59 micros relaxation time is much more strongly
      temperature dependent and has no fluorescence counterpart, indicating an
      activated process with a large energy barrier wherein nonspecific hydrophobic
      interactions between helix A and the G and H helices cause some helix burial but
      Trp14 remains solvent exposed. These results are best fit by a multiple-pathway
      kinetic model when U collapses to form the various folded core structures of E.
      Thus, the results suggest very robust dynamics for core formation involving
      multiple folding pathways and provide significant insight into the primary
      processes of protein folding.

PMID- 11318636
TI  - Enthalpic barriers to the hydrophobic binding of oligosaccharides to phage P22
      tailspike protein.
AB  - The structural thermodynamics of the recognition of complex carbohydrates by
      proteins are not well understood. The recognition of O-antigen polysaccharide by
      phage P22 tailspike protein is a highly suitable model for advancing knowledge in
      this field. The binding to octa- and dodecasaccharides derived from Salmonella
      enteritidis O-antigen was studied by isothermal titration calorimetry and stopped
      flow spectrofluorimetry. At room temperature, the binding reaction is
      enthalpically driven with an unfavorable change in entropy. A large change of 
      1.8 +/- 0.2 kJ mol(-1) K(-1) in heat capacity suggests that the hydrophobic
      effect and water reorganization contribute substantially to complex formation. As
      expected from the large heat-capacity change, we found enthalpy-entropy
      compensation. The calorimetrically measured binding enthalpies were identical
      within error to van't Hoff enthalpies determined from fluorescence titrations.
      Binding kinetics were determined at temperatures ranging from 10 to 30 degrees C.
      The second-order association rate constant varied from 1 x 10(5) M(-1) s(-1) for
      dodecasaccharide at 10 degrees C to 7 x 10(5) M(-1) s(-1) for octasaccharide at
      30 degrees C. The first-order dissociation rate constants ranged from 0.2 to 3.8
      s(-1). The Arrhenius activation energies were close to 50 and 100 kJ mol(-1) for
      the association and dissociation reactions, respectively, indicating mainly
      enthalpic barriers. Despite the fact that this system is quite complex due to the
      flexibility of the saccharide, both the thermodynamic and kinetic data are
      compatible with a simple one-step binding model.

PMID- 11318637
TI  - Three-dimensional structure of 2-amino-3-ketobutyrate CoA ligase from Escherichia
      coli complexed with a PLP-substrate intermediate: inferred reaction mechanism.
AB  - 2-Amino-3-ketobutyrate CoA ligase (KBL, EC 2.3.1.29) is a pyridoxal phosphate
      (PLP) dependent enzyme, which catalyzes the second reaction step on the main
      metabolic degradation pathway for threonine. It acts in concert with threonine
      dehydrogenase and converts 2-amino-3-ketobutyrate, the product of threonine
      dehydrogenation by the latter enzyme, with the participation of cofactor CoA, to
      glycine and acetyl-CoA. The enzyme has been well conserved during evolution, with
      54% amino acid sequence identity between the Escherichia coli and human enzymes.
      We present the three-dimensional structure of E. coli KBL determined at 2.0 A
      resolution. KBL belongs to the alpha family of PLP-dependent enzymes, for which
      the prototypic member is aspartate aminotransferase. Its closest structural
      homologue is E. coli 8-amino-7-oxononanoate synthase. Like many other members of
      the alpha family, the functional form of KBL is a dimer, and one such dimer is
      found in the asymmetric unit in the crystal. There are two active sites per
      dimer, located at the dimer interface. Both monomers contribute side chains to
      each active/substrate binding site. Electron density maps indicated the presence
      in the crystal of the Schiff base intermediate of 2-amino-3-ketobutyrate and PLP,
      an external aldimine, which remained bound to KBL throughout the protein
      purification procedure. The observed interactions between the aldimine and the
      side chains in the substrate binding site explain the specificity for the
      substrate and provide the basis for a detailed proposal of the reaction mechanism
      of KBL. A putative binding site of the CoA cofactor was assigned, and
      implications for the cooperation with threonine dehydrogenase were considered.

PMID- 11318638
TI  - Defining the catalytic metal ion interactions in the Tetrahymena ribozyme
      reaction.
AB  - Divalent metal ions play a crucial role in catalysis by many RNA and protein
      enzymes that carry out phosphoryl transfer reactions, and defining their
      interactions with substrates is critical for understanding the mechanism of
      biological phosphoryl transfer. Although a vast amount of structural work has
      identified metal ions bound at the active site of many phosphoryl transfer
      enzymes, the number of functional metal ions and the full complement of their
      catalytic interactions remain to be defined for any RNA or protein enzyme.
      Previously, thiophilic metal ion rescue and quantitative functional analyses
      identified the interactions of three active site metal ions with the 3'- and 2'
      substrate atoms of the Tetrahymena group I ribozyme. We have now extended these
      approaches to probe the metal ion interactions with the nonbridging pro-S(P)
      oxygen of the reactive phosphoryl group. The results of this study combined with
      previous mechanistic work provide evidence for a novel assembly of catalytic
      interactions involving three active site metal ions. One metal ion coordinates
      the 3'-departing oxygen of the oligonucleotide substrate and the pro-S(P) oxygen
      of the reactive phosphoryl group; another metal ion coordinates the attacking 3'
      oxygen of the guanosine nucleophile; a third metal ion bridges the 2'-hydroxyl of
      guanosine and the pro-S(P) oxygen of the reactive phosphoryl group. These results
      for the first time define a complete set of catalytic metal ion/substrate
      interactions for an RNA or protein enzyme catalyzing phosphoryl transfer.

PMID- 11318639
TI  - Structural analysis of NSAID binding by prostaglandin H2 synthase: time-dependent
      and time-independent inhibitors elicit identical enzyme conformations.
AB  - Nonsteroidal antiinflammatory drugs (NSAIDs) block prostanoid biosynthesis by
      inhibiting prostaglandin H(2) synthase (EC 1.14.99.1). NSAIDs are either rapidly
      reversible competitive inhibitors or slow tight-binding inhibitors of this
      enzyme. These different modes of inhibition correlate with clinically important
      differences in isoform selectivity. Hypotheses have been advanced to explain the
      different inhibition kinetics, but no structural data have been available to test
      them. We present here crystal structures of prostaglandin H(2) synthase-1 in
      complex with the inhibitors ibuprofen, methyl flurbiprofen, flurbiprofen, and
      alclofenac at resolutions ranging from 2.6 to 2.75 A. These structures allow
      direct comparison of enzyme complexes with reversible competitive inhibitors
      (ibuprofen and methyl flurbiprofen) and slow tight-binding inhibitors (alclofenac
      and flurbiprofen). The four inhibitors bind to the same site and adopt similar
      conformations. In all four complexes, the enzyme structure is essentially
      unchanged, exhibiting only minimal differences in the inhibitor binding site.
      These results argue strongly against hypotheses that explain the difference
      between slow tight-binding and fast reversible competitive inhibition by invoking
      global conformational differences or different inhibitor binding sites. Instead,
      they suggest that the different apparent modes of NSAID binding may result from
      differences in the speed and efficiency with which inhibitors can perturb the
      hydrogen bonding network around Arg-120 and Tyr-355.

PMID- 11318640
TI  - The amino-terminal tail of glycogen phosphorylase is a switch for controlling
      phosphorylase conformation, activation, and response to ligands.
AB  - Glycogen phosphorylase is a muscle enzyme which metabolizes glycogen, producing
      glucose-1-phosphate, which can be used for the production of ATP. Phosphorylase
      activity is regulated by phosphorylation/dephosphorylation, and by the allosteric
      binding of numerous effectors. In this work, we have studied 10 site-directed
      mutants of glycogen phosphorylase (GP) in its amino-terminal regulatory region to
      characterize any changes that the mutations may have made on its structure or
      function. All of the GP mutants had normal levels of activity in the presence of
      the allosteric activator AMP. Some of the mutants were observed to have altered
      AMP-binding characteristics, however. R16A and R16E were activated at very low
      AMP concentration and crystallized at low temperature, like the phosphorylated
      form of GP, phosphorylase a, and unlike the dephospho-form, phosphorylase b. This
      indicates that even without phosphorylation, the structures of these mutants are
      more like phosphorylase a than phosphorylase b. These mutants were also very
      poorly phosphorylated in the presence of the inhibitor glucose, while
      phosphorylase b was phosphorylated normally with this inhibitor present. In
      contrast to R16A and R16E, four other mutants behaved like phosphorylase b after
      phosphorylation. R69E was only partially activated by phosphorylation, and I13G,
      R43E, and R43E/R69E were completely inactive after phosphorylation. We propose a
      model for the many functions of the amino terminus to explain the many varied
      effects of these mutations.

PMID- 11318641
TI  - Electron transfer in the substrate-dependent suicide inactivation of lysine 5,6
      aminomutase.
AB  - The lysine 5,6-aminomutase (5,6-LAM) purified from Clostridium sticklandii was
      found to undergo rapid inactivation in the absence of the activating enzyme E(2)
      and ATP. In the presence of substrate, inactivation was also seen for the
      recombinant 5,6-LAM. This adenosylcobalamin-dependent enzyme is postulated to
      generate cob(II)alamin and the 5'-deoxyadenosyl radical through enzyme-induced
      homolytic scission of the Co-C bond. However, the products cob(III)alamin and 5'
      deoxyadenosine were observed upon inactivation of 5,6-LAM. Cob(III)alamin
      production, as monitored by the increase in A(358), proceeds at the same rate as
      the loss of enzyme activity, suggesting that the activity loss is related to the
      adventitious generation of cob(III)alamin during enzymatic turnover. The cleavage
      of adenosylcobalamin to cob(III)alamin is accompanied by the formation of 5'
      deoxyadenosine at the same rate, and the generation of cob(III)alamin proceeds at
      the same rate both aerobically and anaerobically. Suicide inactivation requires
      the presence of substrate, adenosylcobalamin, and PLP. We have ruled out the
      involvement of either the putative 5'-deoxyadenosyl radical or dioxygen in
      suicide inactivation. We have shown that one or more reaction intermediates
      derived from the substrate or/and the product, presumably a radical, participate
      in suicide inactivation of 5,6-LAM through electron transfer from cob(II)alamin.
      Moreover, L-lysine is found to be a slowly reacting substrate, and it induces
      inactivation at a rate similar to that of D-lysine. The alternative substrate
      beta-lysine induces inactivation at least 25 times faster than DL-lysine. The
      inactivation mechanism is compatible with the radical isomerization mechanism
      proposed to explain the action of 5,6-LAM.

PMID- 11318642
TI  - Bacteriophage T7 RNA polymerase transcription elongation is inhibited by site
      specific, stereospecific benzo[c]phenanthrene diol epoxide DNA lesions.
AB  - Benzo[c]phenanthrene diol epoxide (B[c]PhDE), the ultimate carcinogenic
      metabolite of the environmental pollutant benzo[c]phenanthrene, reacts with DNA
      primarily at the exocyclic amino groups of purines, forming B[c]PhDE-DNA adducts
      that differ in their stereochemical configurations and their effect on biological
      processes such as transcription. To determine the effect of these stereoisomers
      on RNA synthesis, in vitro T7 RNA polymerase transcription assays were performed
      using DNA templates modified on the transcribed strand by either a site-specific
      (+)-trans- or (-)-trans-anti-B[c]PhDE-N(6)-dA lesion located within the sequence
      5'-CTCTCACTTCC-3'. The results show that both (-)-trans-anti-B[c]PhDE-N(6)-dA and
      (+)-trans-anti-B[c]PhDE-N(6)-dA block RNA synthesis. Furthermore, both B[c]PhDE
      dA stereoisomeric adducts lead to lower levels of initiation of transcription
      relative to that observed using an unmodified DNA template. In contrast to these
      results, placement of the adduct on the nontranscribed strand within the template
      does not impede transcription elongation. In addition to the assessment of the
      effect of the lesions on transcription elongation, the resulting transcripts were
      characterized in terms of their base composition. A high level of base
      misincorporation is detected at the 3'-ends of truncated transcripts, with
      guanosine being most frequently incorporated opposite the modified nucleotide
      rather than the expected uridine. This result supports the notion that
      translocation past a modified base in a DNA template relies in part on correct
      base incorporation, and suggests that stalling of RNA polymerases at damaged
      sites in DNA may well be dependent on both the presence of the lesion and the
      base which is incorporated opposite the modified nucleotide.

PMID- 11318643
TI  - Nuclear import of Creb and AP-1 transcription factors requires importin-beta 1
      and Ran but is independent of importin-alpha.
AB  - Although the specific role of transcription factors (TFs) is nuclear,
      surprisingly little is known in quantitative terms regarding the pathways by
      which TFs localize in the nucleus. In this study, we use direct binding assays,
      native gel electrophoresis, and fluorescence polarization measurements to show
      for the first time that the cAMP-response element binding protein (CREB) and
      related AP-1 and jun and fos constituents are recognized by importin beta1
      (Impbeta) with nanomolar affinity. We reconstitute the nuclear import of these
      TFs in vitro, demonstrating dependence on cytosolic factors, and show that this
      is due to the requirement for Impbeta, since antibodies to Impbeta, but not to
      importin alpha (Impalpha), inhibit nuclear accumulation significantly. We show
      that Impbeta is necessary and sufficient for docking of CREB at the nuclear
      envelope; that Ran is essential for CREB nuclear import is demonstrated by the
      reduction of nuclear accumulation effected by RanGTPgammaS but not RanGDP, and by
      dissociation of the Impbeta-CREB-GFP complex by RanGTPgammaS but not RanGDP as
      demonstrated using fluorescence polarization assays. The results support the
      existence of an Impbeta1- and Ran-mediated nuclear import pathway for CREB and
      related constitutively nuclear TFs, which is Impalpha-independent and thus
      distinct from import pathways utilized by inducible TFs.

PMID- 11318644
TI  - Actinomycin D binds strongly to d(TGTCATTG), a single-stranded DNA devoid of GpC
      sites.
AB  - Despite the absence of the GpC sequence and complete self-complementarity,
      d(CGTCGTCG) has recently been shown to bind strongly to actinomycin D (ACTD) with
      a binding density of about one drug molecule per strand. To further elucidate the
      nature of such a binding, studies are herein made with single-base G --> A and C 
      -> T replacements in d(CGTCGTCG) to identify the DNA bases that play important
      roles in the strong ACTD binding of this oligomer. On the basis of these results,
      the octamer d(TGTCATTG) has been identified as a potentially strong ACTD binder.
      Indeed, binding titration confirms such an expectation and reveals an ACTD
      binding constant of about 1 x 10(7) M(-1) and a binding density of roughly 0.8
      drug molecule per DNA strand for this strong binding mode. Similar binding
      studies with single-base substitutions on d(TGTCATTG) further reveal the relative
      importance of the C and G bases on its ACTD binding, with the 3'-terminus G
      appearing to be the most crucial base. Further base substitutions lead to the
      conclusion that these C and G bases act in concert rather than individually in
      the ACTD binding of d(TGTCATTG). Spectral comparisons with the apparently single
      stranded GpC-containing d(TGCTTTG) led to the proposal of a speculated monomeric
      hairpin binding model to account for the experimental observations. This model
      makes use of the notion that ACTD prefers to have the 3'-sides of both G bases
      stacking on the opposite faces of its planar phenoxazone chromophore, a principle
      akin to its classic preference for the GpC sequence in duplex form. The finding
      that ACTD can bind strongly to single-stranded DNA of special sequence motifs may
      have important implications.

PMID- 11318645
TI  - Human tissue kallikrein S1 subsite recognition of non-natural basic amino acids.
AB  - We explored the unique substrate specificity of the primary S(1) subsite of human
      urinary kallikrein (hK1), which accepts both Phe and Arg, using internally
      quenched fluorescent peptides Abz-F-X-S-R-Q-EDDnp and Abz-G-F-S-P-F-X-S-S-R-P-Q
      EDDnp [Abz is o-aminobenzoic acid; EDDnp is N-(2,4
      dinitrophenyl)ethylenediamine], which were based on the human kininogen sequence
      at the C-terminal region of bradykinin. Position X, which in natural sequence
      stands for Arg, received the following synthetic basic non-natural amino acids: 4
      (aminomethyl)phenylalanine (Amf), 4-guanidine phenylalanine (Gnf), 4
      (aminomethyl)-N-isopropylphenylalanine (Iaf), N(im)-(dimethyl)histidine [H(2Me)],
      3-pyridylalanine (Pya), 4-piperidinylalanine (Ppa), 4
      (aminomethyl)cyclohexylalanine (Ama), and 4-(aminocyclohexyl)alanine (Aca). Only
      Abz-F-Amf-S-R-Q-EDDnp and Abz-F-H(2Me)]-S-R-Q-EDDnp were efficiently hydrolyzed,
      and all others were resistant to hydrolysis. However, Abz-F-Ama-S-R-Q-EDDnp
      inhibited hK1 with a K(i) of 50 nM with high specificity compared to human plasma
      kallikrein, thrombin, plasmin, and trypsin. The Abz-G-F-S-P-F-X-S-S-R-P-Q-EDDnp
      series were more susceptible to hK1, although the peptides with Gnf, Pya, and Ama
      were resistant to it. Unexpectedly, the peptides in which X is His, Lys, H(2Me),
      Amf, Iaf, Ppa, and Aca were cleaved at amino or at carboxyl sites of these amino
      acids, indicating that the S(1)' subsite has significant preference for basic
      residues. Human plasma kallikrein did not hydrolyze any peptide of this series
      except the natural sequence where X is Arg. In conclusion, the S(1) subsite of
      hK1 accepts amino acids with combined basic and aromatic side chain, although for
      the S(1)-P(1) interaction the preference is for aliphatic and basic side chains.

PMID- 11318646
TI  - Kinetics and thermodynamics of beta 2-microglobulin binding to the alpha 3 domain
      of major histocompatibility complex class I heavy chain.
AB  - The major histocompatibility complex (MHC) class I molecule plays a crucial role
      in cytotoxic lymphocyte function. Functional class I MHC exists as a heterotrimer
      consisting of the MHC class I heavy chain, an antigenic peptide fragment, and
      beta2-microglobulin (beta2m). beta2m has been previously shown to play an
      important role in the folding of the MHC heavy chain without continued beta2m
      association with the MHC complex. Therefore, beta2m is both a structural
      component of the MHC complex and a chaperone-like molecule for MHC folding. In
      this study we provide data supporting a model in which the chaperone-like role of
      beta2m is dependent on initial binding to only one of the two beta2m interfaces
      with class 1 heavy chain. beta2-Microglobulin binding to an isolated alpha3
      domain of the class I MHC heavy chain accurately models the biochemistry and
      thermodynamics of beta2m-driven refolding. Our results explain a 1000-fold
      discrepancy between beta2m binding and refolding of MHC1. The biochemical study
      of the individual domains of complex molecules is an important strategy for
      understanding their dynamic structure and multiple functions.

PMID- 11318647
TI  - Role of intrahelical arginine residues in functional properties of uncoupling
      protein (UCP1).
AB  - The functional role of the four intrahelical arginines in uncoupling protein
      (UCP1) from brown adipose tissue were studied in mutants where they were replaced
      by noncharged residues. Wild-type and mutant UCP1 were expressed in Saccharomyces
      cerevisiae. As measured in isolated UCP1, nucleotide binding was largely lost in
      mutants of R83, R182, and R276 occurring in three repeated domains and common to
      mitochondrial carrier family, whereas mutation of the UCP typical R91 shows
      normal binding capacity but > 20-fold lower binding affinity and a near loss of
      pH dependency of binding. In reconstituted UCP1, fatty acid dependent H(+)
      transport is retained in all four mutants, but inhibition by nucleotide changes
      according to the binding ability of UCP1. Cl(-) transport is inhibited only by
      mutations of arginines in the first domain (R83 and R91). Also in isolated
      mitochondria H(+) transport and respiration with all four mutants is similar to
      wt, and inhibition by GDP is found only in R91T. The three "regular" arginines
      are suggested to influence the nucleotide binding site indirectly via a charge
      network and the "extra" R91 directly via an ion bond with the previously
      characterised pH sensor E190. The mutants were also used to assess intrahelical
      control of UCP1. In the yeast cells expressing UCP1, the aerobic growth could be
      reduced by fatty acid addition only with the nucleotide insensitive mutants. This
      demonstrates an intracellular control of UCP1 by nucleotides and fatty acids.

PMID- 11318648
TI  - Analysis of chimeric receptors shows that multiple distinct functional activities
      of scavenger receptor, class B, type I (SR-BI), are localized to the
      extracellular receptor domain.
AB  - Scavenger receptor BI (SR-BI) mediates the selective uptake of high-density
      lipoprotein (HDL) cholesteryl ester (CE), a process by which HDL CE is taken into
      the cell without degradation of the HDL particle. In addition, SR-BI stimulates
      the bi-directional flux of free cholesterol (FC) between cells and lipoproteins,
      an activity that may be responsible for net cholesterol efflux from peripheral
      cells as well as the rapid hepatic clearance of FC from plasma HDL. SR-BI also
      increases cellular cholesterol mass and alters cholesterol distribution in plasma
      membrane domains as judged by the enhanced sensitivity of membrane cholesterol to
      extracellular cholesterol oxidase. In contrast, CD36, a closely related class B
      scavenger receptor, has none of these activities despite binding HDL with high
      affinity. In the present study, analyses of chimeric SR-BI/CD36 receptors and
      domain-deleted SR-BI have been used to test the various domains of SR-BI for
      functional activities related to HDL CE selective uptake, bi-directional FC flux,
      and the alteration of membrane cholesterol mass and distribution. The results
      show that each of these activities localizes to the extracellular domain of SR
      BI. The N-terminal cytoplasmic tail and transmembrane domains appear to play no
      role in these activities other than targeting the receptor to the plasma
      membrane. The C-terminal tail of SR-BI is dispensable for activity as well for
      targeting to the plasma membrane. Thus, multiple distinct functional activities
      are localized to the SR-BI extracellular domain.

PMID- 11318649
TI  - Electron transfer from heme bL to the [3Fe-4S] cluster of Escherichia coli
      nitrate reductase A (NarGHI).
AB  - We have investigated the functional relationship between three of the prosthetic
      groups of Escherichia coli nitrate reductase A (NarGHI): the two hemes of the
      membrane anchor subunit (NarI) and the [3Fe-4S] cluster of the electron-transfer
      subunit (NarH). In two site-directed mutants (NarGHI(H56R) and NarGHI(H205Y))
      that lack the highest potential heme of NarI (heme b(H)), a large negative
      DeltaE(m,7) is elicited on the NarH [3Fe-4S] cluster, suggesting a close
      juxtaposition of these two centers in the holoenzyme. In a mutant retaining heme
      b(H), but lacking heme b(L) (NarGHI(H66Y)), there is no effect on the NarH [3Fe
      4S] cluster redox properties. These results suggest a role for heme b(H) in
      electron transfer to the [3Fe-4S] cluster. Studies of the pH dependence of the
      [3Fe-4S] cluster, heme b(H), and heme b(L) E(m) values suggest that significant
      deprotonation is only observed during oxidation of the latter heme (a pH
      dependence of -36 mV pH(-1)). In NarI expressed in the absence of NarGH
      [NarI(DeltaGH)], apparent exposure of heme b(H) to the aqueous milieu results in
      both it and heme b(L) having E(m) values with pH dependencies of approximately 
      30 mV pH(-1). These results are consistent with heme b(H) being isolated from the
      aqueous milieu and pH effects in the holoenzyme. Optical spectroscopy indicates
      that inhibitors such as HOQNO and stigmatellin bind and inhibit oxidation of heme
      b(L) but do not inhibit oxidation of heme b(H). Fluorescence quench titrations
      indicate that HOQNO binds with higher affinity to the reduced form of NarGHI than
      to the oxidized form. Overall, the data support the following model for electron
      transfer through the NarI region of NarGHI: Q(P) site --> heme b(L) --> heme b(H)
      --> [3Fe-4S] cluster.

PMID- 11318650
TI  - Electron and proton transfer in the arginine-54-methionine mutant of cytochrome c
      oxidase from Paracoccus denitrificans.
AB  - Arginine 54 in subunit I of cytochrome c oxidase from Paracoccus denitrificans
      interacts with the formyl group of heme a. Mutation of this arginine to
      methionine (R54M) dramatically changes the spectral properties of heme a and
      lowers its midpoint redox potential [Kannt et al. (1999) J. Biol. Chem. 274,
      37974-37981; Lee et al. (2000) Biochemistry 39, 2989-2996; Riistama et al. (2000)
      Biochim. Biophys. Acta 1456, 1-4]. During anaerobic reduction of the mutant
      enzyme, a small fraction of heme a is reduced first along with heme a(3), while
      most of heme a is reduced later. This suggests that electron transfer is impaired
      thermodynamically due to the low redox potential of heme a but that it still
      takes place from Cu(A) via heme a to the binuclear site as in wild-type enzyme,
      with no detectable bypass from Cu(A) directly to the binuclear site. Consistent
      with this, the proton translocation efficiency is unaffected at 1 H(+)/e(-) in
      the mutant enzyme, although turnover is strongly inhibited. Time-resolved
      electrometry shows that when the fully reduced enzyme reacts with O(2), the fast
      phase of membrane potential generation during the P(R )()--> F transition is
      unaffected by the mutation, whereas the slow phase (F --> O transition) is
      strongly decelerated. In the 3e(-)-reduced mutant enzyme heme a remains oxidized
      due to its lowered midpoint potential, whereas Cu(A) and the binuclear site are
      reduced. In this case the reaction with O(2) proceeds via the P(M) state because
      transfer of the electron from Cu(A) to the binuclear site is delayed. The single
      phase of membrane potential generation in the 3e(-)-reduced mutant enzyme, which
      thus corresponds to the P(M)--> F transition, is decelerated, but its amplitude
      is comparable to that of the P(R)--> F transition. From this we conclude that the
      completely (4e(-)) reduced enzyme is fully capable of proton translocation.

PMID- 11318651
TI  - Parameters affecting the restoration of activity to inactive mutants of
      thymidylate synthase via subunit exchange: further evidence that thymidylate
      synthase is a half-of-the-sites activity enzyme.
AB  - In a previous study we demonstrated that Escherichia coli thymidylate synthase
      activity could be restored completely by incubating basically inactive mutants of
      this enzyme at room temperature with R(126)E, another inactive mutant [Maley, F.,
      Pedersen-Lane, J., and Changchien, L.-M. (1995) Biochemistry 34, 1469-1474].
      Since only one of the enzyme's two subunits possessed a functional active site
      and the restoration of activity could be titrated to be equivalent to that of the
      wild-type enzyme's specific activity, it was proposed that thymidylate synthase
      was a half-of-the-sites activity enzyme. We now provide additional support for
      this thesis by presenting an in-depth analysis of some conditions affecting the
      restoration of enzyme activity. For this purpose, we employed two mutants with
      marginal thymidylate synthase activity, Y(94)A and R(126)E. The parameters that
      were examined included pH, concentration of protein, temperature, and urea
      concentration, all of which influenced the rate of activity restoration. It was
      found, surprisingly, that by maintaining the amount of each protein constant,
      while increasing the volume of solution, the rate and total activity restored was
      greatly enhanced. Increasing the pH from 6.0 to 9.0 markedly increased the rate
      at which the optimal activity was restored, as did increasing the temperature
      from 4 to 40 degrees C. A similar effect was obtained when the incubation of the
      mutants was conducted at 4 degrees C in the presence of 1.5 M urea, a temperature
      at which activity is restored extremely slowly. Raising the pH to 9.0 resulted in
      an almost instantaneous restoration of activity at 4 degrees C. The manner in
      which thymidylate synthase activity is restored from the mutants in the presence
      of varying concentrations of ethanol, ethylene glycol, and glycerol suggests that
      changes in subunit interaction and enzyme conformation are in part responsible
      for the observed differences. Most significantly, at solution levels of 10%,
      ethanol was found to activate, while ethylene glycol inhibited slightly and
      glycerol was somewhat more inhibitory. At a concentration of 20%, ethanol
      inhibited rather strikingly, ethylene glycol was slightly more inhibitory than at
      10%, and glycerol was strongly inhibitory. Since the net result of these findings
      is the suggestion that the restoration of thymidylate synthase activity is due to
      a separation of the mutant dimers into their respective subunits, followed by
      their recombination to an active heterodimer, evidence for this phenomenon was
      sought by separating the recombined dimers using nondenaturating polyacrylamide
      gel electrophoresis. Sequence analysis of the isolated homo- and heterodimers
      clearly demonstrated that the active enzyme is a product of subunit exchange, one
      that is very efficient relative to the wild-type enzyme, which did not exchange
      subunits unless denatured.

PMID- 11318653
TI  - Evidence for protein dielectric relaxations in reaction centers associated with
      the primary charge separation detected from Rhodospirillum rubrum chromatophores
      by combined photovoltage and absorption measurements in the 1-15 ns time range.
AB  - Fast photovoltage measurements in Rhodospirillum rubrum chromatophores in the
      nanosecond time range, escorted by time-resolved absorption measurements, are
      described. Under reducing conditions, the photovoltage decayed significantly
      faster than the spectroscopically detected charge recombination of the radical
      pair P(+)H(A)(-). This indicates the occurrence of considerable dielectric
      relaxations. Our data and data from the literature were analyzed by means of a
      reaction scheme consisting of three states, namely, A, P, and P(+)H(A)(-). A time
      dependent DeltaG(t) was introduced by assuming a time-dependent rate constant of
      the back-reaction, k(-1)(t). With the exception of the latter rate constant, all
      other parameters of the model are reliably known within narrow limits. This
      allowed us to distinguish between the three cases assumed for DeltaG degrees (t):
      (1)DeltaG degrees (t) = constant; (2)DeltaG degrees (t) as published by Peloquin
      et al. [Peloquin, J. M., Williams, J. C., Lin, X. M., Alden, R. G., Taguchi, A.
      K. W., Allen, J. P., and Woodbury, N. W. (1994) Biochemistry 33, 8089-8100]; and
      a (3)DeltaG degrees (t) that fits the present data. The assumption that (1)DeltaG
      degrees (t) = constant is incompatible with our photovoltage data, and (2)DeltaG
      degrees (t) is incompatible with the constraint that the ratio of fluorescence
      yields in the closed and open state is F(m)/F(o) approximately 2. We specify a
      (3)DeltaG degrees (t) that should be valid for photosynthetic reaction centers in
      vivo. Furthermore, the overall kinetics of the electric relaxation, e(t), in
      response to the primary charge separation were determined.

PMID- 11318652
TI  - How Ala-->Gly mutations in different helices affect the stability of the
      apomyoglobin molten globule.
AB  - The apomyoglobin molten globule has a complex, partly folded structure with a
      folded A[B]GH subdomain; the factors determining its stability are not yet known
      in detail. Ala-->Gly mutations, made at solvent-exposed positions, are used to
      probe the role of helix propensity of individual helices in stabilizing the
      molten globule. Molten globule stability is measured by reversible urea
      unfolding, monitored both by circular dichroism and by tryptophan fluorescence.
      Two-state unfolding is tested by superposition of these two unfolding curves, and
      stability data are reported only for variants which satisfy the superposition
      test. Results for sites Q8 in the A helix and E109 in the G helix confirm that
      the helix propensities of the A and G helices both strongly affect molten globule
      stability, in contrast to results for the G65A/G73A double mutant which show that
      changing the helix propensity of the E-helix sequence has no significant
      stabilizing effect. Changing the helix propensity of the B-helix sequence with
      the G23A/G25A double mutant affects molten globule stability to an intermediate
      extent, confirming an earlier report that this mutant has increased stability.
      These results are consistent with the bipartite structure for the molten globule
      in which the A, G, and H helices are stably folded, while the long E helix is
      unfolded and the B helix has intermediate stability. Some differences are found
      in the shapes of the unfolding curves of different mutants even though they
      satisfy the superposition test for two-state unfolding, and possible explanations
      are discussed.

PMID- 11318654
TI  - A photolysis-triggered heme ligand switch in H93G myoglobin.
AB  - Resonance Raman spectroscopy and step-scan Fourier transform infrared (FTIR)
      spectroscopy have been used to identify the ligation state of ferrous heme iron
      for the H93G proximal cavity mutant of myoglobin in the absence of exogenous
      ligand on the proximal side. Preparation of the H93G mutant of myoglobin has been
      previously reported for a variety of axial ligands to the heme iron (e.g.,
      substituted pyridines and imidazoles) [DePillis, G., Decatur, S. M., Barrick, D.,
      and Boxer, S. G. (1994) J. Am. Chem. Soc. 116, 6981-6982]. The present study
      examines the ligation states of heme in preparations of the H93G myoglobin with
      no exogenous ligand. In the deoxy form of H93G, resonance Raman spectroscopic
      evidence shows water to be the axial (fifth) ligand to the deoxy heme iron.
      Analysis of the infrared C-O and Raman Fe-C stretching frequencies for the CO
      adduct indicates that it is six-coordinate with a histidine trans ligand.
      Following photolysis of CO, a time-dependent change in ligation is evident in
      both step-scan FTIR and saturation resonance Raman spectra, leading to the
      conclusion that a conformationally driven ligand switch exists in the H93G
      protein. In the absence of exogenous nitrogenous ligands, the CO trans effect
      stabilizes endogenous histidine ligation, while conformational strain favors the
      dissociation of histidine following photolysis of CO. The replacement of
      histidine by water in the five-coordinate complex is estimated to occur in < 5
      micros. The results demonstrate that the H93G myoglobin cavity mutant has
      potential utility as a model system for studying the conformational energetics of
      ligand switching in heme proteins such as those observed in nitrite reductase,
      guanylyl cyclase, and possibly cytochrome c oxidase.

PMID- 11318655
TI  - Neuregulin-1-stimulated phosphorylation of GABP in skeletal muscle cells.
AB  - Localization of acetylcholine receptors (AChRs) to neuromuscular synapses is
      mediated, in part, through selective transcription of AChR genes in myofiber
      synaptic nuclei. Neuregulin-1 (NRG-1) is a good candidate for the extracellular
      signal that induces synapse-specific gene expression, since NRG-1 is concentrated
      at synaptic sites and activates AChR synthesis in cultured muscle cells. NRG-1
      induced transcription requires activation of Erk and Jnk MAP kinases, but the
      downstream substrates that mediate this transcriptional response are not known.
      Previous studies have demonstrated that a consensus binding site for Ets proteins
      is required both for NRG-1-induced transcription and for synapse-specific
      transcription in transgenic mice. This regulatory element binds GABPalpha, an Ets
      protein, and GABPbeta, a protein that dimerizes with GABPalpha, raising the
      possibility that phosphorylation of GABP by MAP kinases induces transcription of
      AChR genes. To determine whether MAP kinases might directly regulate the activity
      of GABP, we studied MAP kinase-catalyzed and NRG-1-induced phosphorylation of
      GABPalpha and GABPbeta. We show that GABPalpha and GABPbeta are phosphorylated in
      vitro by Erk and by Jnk. Using recombinant proteins containing mutated serine and
      threonine resides, we show that GABPalpha is phosphorylated predominantly at
      threonine 280, while serine 170 and threonine 180 are the major phosphorylation
      sites in GABPbeta. We generated antibodies specific to the major phosphorylation
      site in GABPalpha and show that NRG-1 stimulates phosphorylation of GABPalpha at
      threonine 280 in vivo. These results suggest that GABPalpha is a target of MAP
      kinases in NRG-1-stimulated muscle cells and are consistent with the idea that
      phosphorylation of GABPalpha contributes to transcriptional activation of AChR
      genes by NRG-1.

PMID- 11318656
TI  - Yersiniabactin synthetase: probing the recognition of carrier protein domains by
      the catalytic heterocyclization domains, Cy1 and Cy2, in the chain-initiating
      HWMP2 subunit.
AB  - The HMWP2 subunit of yersiniabactin (Ybt) synthetase, a 230 kDa nonribosomal
      peptide synthetase (NRPS) making the N-terminus of the Ybt siderophore of
      Yersinia pestis, has one cysteine-specific adenylation (A) domain, three carrier
      protein domains (ArCP, PCP1, PCP2), and two heterocyclization domains (Cy1, Cy2).
      The A domain loads the two PCP domains with cysteines that get heterocyclized by
      the Cy domains to yield a tricyclic hydroxyphenylthiazolinylthiazolinyl (HPTT)
      chain lodged in thioester linkage to the PCP2 domain. The interdomain recognition
      by the Cy1 and Cy2 domains for the three carrier proteins was tested using
      inactivating mutations at the conserved serine that is phosphopantetheinylated in
      each carrier domain (S52A, S1439A, and S1977A). These mutant forms of HMWP2 were
      tested for in trans complementation by carrier protein fragments: holo-ArCPs
      (S52A), holo-PCP1 and analogues (S1439A), and holo-PCP2 and analogues (S1977A).
      The S52A mutant tests the recognition of the Cy1 domain for donor acyl-ArCP
      substrates, while the S1439A mutant tests the specificity of the same Cy1 domain
      for downstream substrates presented by distinct PCPs. The S1439A likewise tests
      the recognition of Cy2 for its upstream PCP-tethered acyl donor. The S1977A
      mutant analogously tests the Cy2 domain for downstream Cys-PCP recognition. In
      all cases in trans complementation was successful with the carrier protein
      fragments, allowing kinetic probes of catalytic efficiency for PCP scaffolds and
      for uncoupling of the condensation and heterocyclization functions of Cy1 and
      Cy2. Overall, the Cy domains tested showed a definite selectivity for the
      upstream protein scaffold but were more relaxed toward the downstream acceptor
      protein. This work points to the importance of protein-protein interactions in
      mediating directional chain growth in NRPS and presents the first systematic
      exploration of how the protein scaffolds affect catalytic efficiency.

PMID- 11318657
TI  - Inhibition of GDP/GTP exchange on G alpha subunits by proteins containing G
      protein regulatory motifs.
AB  - A novel Galpha binding consensus sequence, termed G-protein regulatory (GPR) or
      GoLoco motif, has been identified in a growing number of proteins, which are
      thought to modulate G-protein signaling. Alternative roles of GPR proteins as
      nucleotide exchange factors or as GDP dissociation inhibitors for Galpha have
      been proposed. We investigated the modulation of the GDP/GTP exchange of
      Gialpha(1), Goalpha, and Gsalpha by three proteins containing GPR motifs (GPR
      proteins), LGN-585-642, Pcp2, and RapIGAPII-23-131, to elucidate the mechanisms
      of GPR protein function. The GPR proteins displayed similar patterns of
      interaction with Gialpha(1) with the following order of affinities: Gialpha(1)GDP
      >> Gialpha(1)GDPAlF(4)(-) > or = Gialpha(1)GTPgammaS. No detectable binding of
      the GPR proteins to Gsalpha was observed. LGN-585-642, Pcp2, and RapIGAPII-23-131
      inhibited the rates of spontaneous GTPgammaS binding and blocked GDP release from
      Gialpha(1) and Goalpha. The inhibitory effects of the GPR proteins on Gialpha(1)
      were significantly more potent, indicating that Gi might be a preferred target
      for these modulators. Our results suggest that GPR proteins are potent GDP
      dissociation inhibitors for Gialpha-like Galpha subunits in vitro, and in this
      capacity they may inhibit GPCR/Gi protein signaling in vivo.

PMID- 11318748
TI  - Coronary artery bypass grafting in patients on chronic hemodialysis in Japan.

PMID- 11318749
TI  - Coronary artery bypass grafting for hemodialysis-dependent patients.
AB  - Patients with end-stage renal disease carry a risk of coronary atherosclerosis.
      This study was performed to evaluate the perioperative and remote data of
      coronary artery bypass grafting (CABG) in hemodialysis dependent patients. We
      retrospectively analyzed the results of isolated CABG performed at Shin-Tokyo
      Hospital between June 1, 1993 and May 31, 2000. Preoperative, perioperative, and
      follow-up data of the patients on hemodialysis (Group HD, n = 37) were collected
      and compared with those of control patients (Group C, n = 1,639). Group HD
      consisted of 26 males and 11 females with a mean age of 59.9 +/- 8.1 years, and
      the mean number of bypasses was 2.5 +/- 1.1. Group HD had a longer postoperative
      intubation time, ICU stay, and hospital stay than Group C. The postoperative
      major complication rate in Group HD (18.9%) was not significantly different from
      that in Group C (11.3%). However, the inhospital mortality rate in Group HD
      (5.4%) was higher than Group C (0.6%). At the mean follow-up of 2.4 years, the
      actuarial 3-year survival of Groups HD and C were 90.6% and 97.6%, respectively
      (p < 0.001), excluding hospital mortality. The actuarial 3-year cardiac event
      free rates were 84.3% in Group HD and 88.8% in Group C, showing no difference.
      Patients on chronic hemodialysis carry a significant risk of prolonged inhospital
      care and hospital death. Once successful surgical revascularization was
      completed, their long-term cardiac events could be controlled as effectively. The
      increased distant death rates was probably associated with the nature of renal
      disease.

PMID- 11318750
TI  - Coronary artery bypass grafting for dialysis patients: usefulness of
      multiarterial bypass.
AB  - This study assessed the efficacy of multiarterial bypass in coronary artery
      bypass grafting (CABG) in dialysis patients. Eighty dialysis patients who
      underwent CABG were divided into 2 groups. Group A consisted of 38 patients in
      whom the left internal thoracic artery and additional saphenous vein graft (SVG)
      had been used. Group B consisted of 42 patients in whom 2 or 3 arterial grafts
      and additional SVGs had been used. No mediastinitis was shown in either group.
      Actuarial survival rates, including all deaths, and estimated by cardiac deaths
      at 8 years, were 28% and 83%, respectively, in Group A and 93% and 100%,
      respectively, in Group B with a significant difference (p = 0.014 and 0.016,
      respectively). Cardiac event-free rates at 8 years were 43% and 96% in Groups A
      and B, respectively, with a significant difference (p = 0.0016). Multiarterial
      grafting improved long-term results after CABG for dialysis patients compared
      with single internal thoracic artery grafting with minimal complications related
      to graft harvesting.

PMID- 11318751
TI  - Immediate and long-term results of coronary artery bypass operation in
      hemodialysis patients.
AB  - This study evaluated the early and late results of coronary artery bypass
      grafting (CABG) in patients on long-term maintenance hemodialysis (chronic HD) at
      Teikyo University Ichihara Hospital between January 1996 and June 2000. Thirty
      six patients on chronic HD underwent CABG. There were 26 males (72%) and 10
      females (28%) ranging from 41 to 81 years (mean +/- SD, 61.8 +/- 9.2 years) of
      age. Twenty-one patients (58%) had unstable angina, 14 (39%) stable angina, and 1
      acute myocardial infarction. Eleven patients (31%) had urgent or emergency CABG.
      The average graft number was 2.5 +/- 0.8 (arterial graft 1.3 +/- 0.7/patient).
      Six patients had concomitant cardiac operations. Three patients underwent re- or
      a second re-CABG. Five patients underwent off-pump CABG. Principally, HD was
      performed during cardiopulmonary bypass and was followed by continuous
      hemodiafiltration in the early postoperative period. The early mortality was 11%;
      25% in emergency and urgent CABG and 4% in elective CABG. In the follow-up period
      between 1 and 53 months (mean +/- SD 21.9 +/- 15.1 months), 4 patients died, and
      9 patients developed recurrence of angina pectoris (6, occlusion of saphenous
      vein graft and 3, native coronary progression). Six patients had coronary
      intervention. The postoperative angiogram showed that all arterial grafts were
      patent, but the patency of the vein grafts was only 61.5%. The early results of
      CABG in patients on chronic HD was satisfactory. The late recurrence of angina
      pectoris mostly was caused by occlusion of the saphenous vein graft. In
      conclusion, the aggressive use of arterial grafts is crucial in CABG for patients
      on chronic HD.

PMID- 11318752
TI  - Coronary artery bypass in dialysis patients.
AB  - This study evaluated the operative outcome of dialysis patients undergoing
      coronary artery bypass (CAB). In the past 6 years, 38 dialysis patients with a
      mean age of 57.5 years underwent CAB. Thirty-one operations were elective, and 7
      were nonelective operations. Thirty-two operations were performed under cardiac
      arrest, 3 operations were performed under fibrillatory arrest, and 3 operations
      were performed without cardiopulmonary bypass. The average number of bypass
      grafts was 2.8. In all patients, the internal thoracic artery was used. Hospital
      mortality was 5.3%. Actuarial survival rates at 1, 3, and 5 years including all
      causes of death were 88%, 80%, and 72%, respectively. With improvements in
      perioperative management, coronary artery bypass can be performed with acceptable
      mortality and morbidity in dialysis patients. Complete revascularization without
      cardiopulmonary bypass is the ideal method and will increase in usage. However,
      the conventional CAB also provides acceptable results.

PMID- 11318753
TI  - Coronary artery bypass grafting in patients with dialysis-dependent renal
      failure.
AB  - This study identified preoperative characteristics of dialysis patients
      undergoing coronary artery bypass grafting (CABG) and determined the early and
      long-term results. We retrospectively analyzed the data of 60 patients (mean age
      60.8 +/- 7.6 years) with end-stage renal disease who underwent CABG between 1982
      and 1999. Seventeen (28%) patients underwent CABG for unstable angina, and 9
      (15%) patients required preoperative intraaortic balloon pumping. The incidence
      of congestive heart failure (18%) and diseased aorta (42%) was higher in the
      dialysis group. In-hospital mortality in the dialysis group was 13% (8/60). The
      estimated survival rate at 5 and 10 years in the dialysis patients was 55.6 +/-
      8.8% and 31.8 +/- 11.6%, respectively. The cardiac event-free rate, excluding the
      in-hospital mortality, was 62.5 +/- 9.9% at 5 years. Although the early and long
      term results of CABG in dialysis patients were inferior to those of nondialysis
      patients, CABG in dialysis-dependent patients allows the patients to continue
      their dialysis therapy and to improve their functional status.

PMID- 11318754
TI  - Coronary artery bypass grafting in patients with dialysis-dependent renal
      failure.
AB  - The aim of this study was to define short- and long-term results of coronary
      artery bypass grafting (CABG) in dialysis patients. A retrospective review was
      carried out on 73 consecutive patients dependent on chronic dialysis who
      underwent CABG. In 63 isolated CABGs, 9 operations were performed under normal
      beating heart because of severe atherosclerotic changes in the ascending aorta or
      carotid arteries. The operative mortality (30 days' mortality) was 4.1%, and
      causes of death were closely related to cardiopulmonary bypass use. In the last
      29 operations after introduction of the beating heart bypass, no hospital deaths
      occurred. The actual survival rates dropped to 45% at 70 months mainly for
      noncardiac late death. CABG for dialysis patients as undertaken with an
      acceptable operative risk. Extended application of beating heart bypass to these
      patients may produce further positive early results.

PMID- 11318755
TI  - Coronary artery bypass grafting in 105 patients with hemodialysis-dependent renal
      failure.
AB  - This study was proposed to define early and long-term results of coronary artery
      bypass grafting (CABG) in dialysis-dependent renal failure (RF) patients, and
      preoperative patient characteristics. This study included 105 patients (87 males
      and 18 females; mean age 60.0 +/- 9.0 years, range 39-79) with RF on maintenance
      dialysis (hemodialysis 100, peritoneal dialysis 5) who underwent isolated CABG
      between August 1985 and April 2000. Postoperative follow-up was completed in 100%
      and averaged 3.1 years. There were 22 emergency and 2 re-CABG cases. Previous
      myocardial infarction (MI) was found in 55 patients (52%), and unstable angina
      was noted in 53 patients (50%). Diabetes mellitus was the cause of RF in 50
      patients (48%; 24 patients required insulin). There was 1 case of single vessel
      disease, 31 cases of double vessel disease, 54 cases of triple vessel disease,
      and 19 cases of left main disease. Preoperative left ventriculography was
      performed in 92 patients (88%). Left ventricular ejection fraction (LVEF) was
      48.3 +/- 15.8% (range 11-74%) and was 40% or less in 25 patients (27%). The mean
      number of distal anastomoses was 2.5 (range 1-5). Three patients received only
      vein grafts, but all were cases of emergency CABG. The remaining 102 patients
      (97%) received at least 1 arterial conduit. Among them, 64 patients received only
      arterial conduits, and 72 patients received 2 or more distal anastomoses with
      arterial conduits. Five patients (4.8%) died within 30 days after CABG (2 cardiac
      deaths and 3 noncardiac deaths), and 8 patients (7.6%) died beyond 30 days after
      CABG before discharge (all noncardiac deaths). The cause of 2 cardiac deaths was
      abrupt circulatory collapse during or after hemodialysis in patients with severe
      left ventricular dysfunction (LVEF; 11% and 28%) in the early postoperative
      period. The causes of 8 noncardiac deaths included infection in 4 and rupture of
      aortic aneurysm, stroke, sleep apnea syndrome, and mesenteric infarction. During
      the follow-up period, there were 29 late deaths (8 cardiac, 13 noncardiac, and 8
      sudden death), 6 MIs, 13 percutaneous transluminal coronary angioplasty, and 1 re
      CABG. The 5-year actuarial survival rate was 59.8%, the cardiac death-free rate
      was 83.0%, and the cardiac event-free rate was 62.4%. Although CABG in patients
      on hemodialysis is associated with high early and long-term mortality in terms of
      both cardiac and noncardiac deaths in proportion to the severity of the
      preoperative condition, long-term survival was still better than that of general
      dialysis patients. Meticulous perioperative management may be the key factor in
      the improvement of early results.

PMID- 11318757
TI  - Experimental study of small arterial anastomosis with gelatin-resorcin
      formaldehyde glue and collagen sheet.
AB  - In cardiovascular surgery, the manual continuous suture has often been used for
      microvascular anastomosis, but the luminal irregularity often causes thrombotic
      stenosis in the anastomosis sites. The purpose of this study was to examine the
      feasibility of the combined use of gelatin-resorcin-formaldehyde (GRF) glue and a
      collagen sheet for the anastomosis of small arteries 3 to 4 mm in diameter in
      experimental animals. End-to-end anastomoses of the carotid and femoral arteries
      of mongrel dogs were carried out with the combined use of GRF glue and collagen
      sheet. The physical strength of the anastomosis, the histopathologic condition of
      the vassels, and the absorptivity and the inflammatory response of the glue were
      evaluated. The physical strength of the anastomosis sites was good and their
      flexibility optimal, the smooth luminal surface appeared excellent for preventing
      thrombotic stenosis in all follow-up periods, and the glue was absorbed almost
      completely within 12 weeks postoperatively. The combined use of GRF glue and
      collagen sheet would be feasible for the anastomosis of small arteries 3 to 4 mm
      in diameter and could substitute for the conventional suture method.

PMID- 11318756
TI  - Efficacy of nonwoven fabric bioreactor immobilized with porcine hepatocytes for
      ex vivo xenogeneic perfusion treatment of liver failure in dogs.
AB  - We have developed a new bioartificial liver bioreactor filled with porcine
      hepatocytes immobilized on polyester nonwoven fabric (NWF). In this study, we
      investigated the efficacy of our hybrid bioartificial liver system incorporating
      the NWF bioreactors and an immunoglobulin adsorbent column for perfusion
      treatment in a canine liver failure model. Xenogeneic perfusion treatment for
      operative canine liver failure models were performed for 3 h, and survival time,
      intracranial pressure, and blood and cerebrospinal fluid data were documented.
      Treatment was carried out without obstruction by immunological rejection when
      immunoglobulin adsorbent columns were used with the NWF bioreactors in
      combination. Dogs treated with this system exhibited a restricted increase of
      intracranial pressure and significant compensatory effects on blood and
      cerebrospinal amino acid imbalances as shown by a significant improvement of
      Fischer's ratio. On the other hand, relatively low capacity for ammonia
      elimination was shown as compared with homologous direct hemoperfusion.

PMID- 11318758
TI  - Laser Doppler velocimetry and flow visualization studies in the regurgitant
      leakage flow region of three mechanical mitral valves.
AB  - Streak line flow visualization and laser Doppler velocimetry (LDV) were conducted
      in the regurgitant leakage flow region of 3 mechanical heart valve types:
      CarboMedics, Medtronic Hall, and St. Jude Medical. Streak line flow visualization
      identified regions of high regurgitant flow, and LDV measurements were focused on
      those locations. Maximum regurgitant flow velocities after valve closure ranged
      from 0.7 to 2.6 m/s, and maximum Reynolds shear stress after valve closure ranged
      from 450 to 3,600 dyne/cm2. These data indicate that leakage flows can generate
      turbulent jets with elevated Reynolds stresses even in bileaflet valves.

PMID- 11318759
TI  - Blood product use during routine open heart surgery: the impact of the
      centrifugal pump.
AB  - A prospective randomized study was done including 1,000 patients undergoing
      routine open heart surgery. Patients were randomly assigned to either a roller
      pump or a BioMedicus centrifugal pump with identical extracorporeal circuits.
      There were no significant differences between study groups. Actual blood products
      transfused and predicted transfusion requirements (using Cardiac RiskMaster) were
      examined as was chest tube drainage (CTD). The predicted transfusion requirement
      was 885 of 1,000 patients. Transfusions were required by 472 of 1,000. Risk
      factors as significant predictors of increased CTD and use of blood products were
      emergency surgery status, increased cross-clamp time, and higher predicted risk
      of mortality. The only significant predictor of decreased CTD was the use of a
      centrifugal pump. Predictors of increased length of stay were myocardial
      infarction, preoperative urea, age, and massive transfusion. Data provide
      evidence that use of the centrifugal pump improves patient outcomes by decreasing
      CTD and decreasing the requirements for transfusion, which results in a shorter
      hospital stay.

PMID- 11318760
TI  - Assessment of skeletal muscle ventricle tissue blood flow using positron emission
      tomography.
AB  - In this pilot study, we assessed the feasibility of using positron emission
      tomography (PET) imaging for in vivo measurement of skeletal muscle ventricle
      (SMV) tissue blood flow. In 4 dogs, with SMVs prepared from their latissimus
      dorsi muscle, we quantified SMV tissue blood flow by PET and related it to the
      tissue flow measured by radiolabeled microspheres under similar physiologic
      conditions. The tissue blood flow was estimated in SMVs wrapped around a mandrel
      (not in circulation) at rest and during SMV stimulation (30 and 90 contraction
      cycles/min). SMV tissue perfusion was heterogeneous, especially during SMV
      contraction. Furthermore, there was a linear relationship between SMV tissue
      flows estimated by PET and those measured by microspheres. We conclude that in
      vivo imaging of SMV is feasible by PET. Quantification of SMV tissue blood flow
      by PET has promise as a means of assessing changes in blood flow, but further
      technical progress needs to be made before absolute flows can be reliably
      measured.

PMID- 11318761
TI  - Metabolic alkalosis in a hemodialysis patient after ingestion of a large amount
      of an antacid medication.
AB  - A maintenance hemodialysis patient developed metabolic alkalosis in the absence
      of vomiting or nasogastric suction. The cause of the metabolic alkalosis was
      ingestion of an exogenous alkali in the form of Bromoseltzer. The metabolic
      alkalosis improved with hemodialysis using a low-bicarbonate bath.

PMID- 11318763
TI  - Methods to identify drug deposition in the lungs following inhalation.

PMID- 11318764
TI  - The role of therapeutic drug monitoring in treatment of HIV infection.

PMID- 11318765
TI  - Lack of effect of ondansetron on the pharmacokinetics and analgesic effects of
      morphine and metabolites after single-dose morphine administration in healthy
      volunteers.
AB  - AIMS: The purpose of this investigation was to study the influence of ondansetron
      on the single-dose pharmacokinetics and the analgesic effects elicited by
      morphine and the 3- and 6-glucuronide metabolites of morphine in healthy
      volunteers. METHODS: This was a randomized, double-blind, placebo-controlled, two
      way crossover study in which six male and six female subjects were administered a
      single 10 mg intravenous dose of morphine sulphate, followed 30 min later by a
      single 16 mg intravenous dose of ondansetron hydrochloride or placebo. Serum and
      urine concentrations of morphine, morphine-3-glucuronide (M3G) and morphine-6
      glucuronide (M6G) samples were quantified over 48 h using high performance liquid
      chromatography with detection by mass spectrometry. Analgesia was assessed in the
      volunteers with a contact thermode device to provide a thermal pain stimulus.
      Four analgesic response variables were measured including thermal pain threshold,
      thermal pain tolerance, temporal summation of pain and mood state. RESULTS: The
      two treatments appeared to be equivalent based on the 90% confidence intervals
      (0.6, 1.67) of the least squares means ratio. All least squares means ratio
      confidence intervals for each parameter, for each analyte fell within the
      specified range, demonstrating a lack of an interaction. CONCLUSIONS: The results
      of this study suggest that administration of ondansetron (16 mg i.v.) does not
      alter the pharmacokinetics of morphine and its 3- or 6-glucuronide metabolites to
      a clinically significant extent, nor does it affect the overall analgesic
      response to morphine as measured by the contact thermode system.

PMID- 11318766
TI  - Dose requirement and prolactin elevation of antipsychotics in male and female
      patients with schizophrenia or related psychoses.
AB  - AIMS: The aim of this study was to investigate the prolactin (PRL) secretion and
      the growth hormone (GH)-insulin-like growth factor I (IGF-I) axis in relation to
      gender and side-effects and dose of antipsychotic drugs during long-term
      treatment. METHODS: Forty-seven patients (21 men and 26 women), diagnosed with
      schizophrenia or related psychoses according to the Diagnostic and Statistical
      Manual of Mental Disorders (DSM-IV) criteria and treated with different classical
      antipsychotics, were studied. Prolactin, GH and IGF-I were measured, as well as
      the serum concentration of the antipsychotics. In addition, body mass index (BMI)
      was calculated. RESULTS: The median daily, as well as the median body weight,
      adjusted daily dose of antipsychotic drugs was twofold higher in male compared
      with female patients. Antipsychotic-induced hyperprolactinaemia was more frequent
      and occurred at a lower daily dose of antipsychotics in women. Irrespective of
      sex, more than half of the patients had elevated BMI. Two patients had a slight
      increment in IGF-I levels, whereas the GH concentration, as assessed on a single
      occasion, was normal in all patients. CONCLUSIONS: Patients on long-term
      antipsychotic therapy, with doses adjusted according to therapeutic efficiency,
      exhibited hyperprolactinaemia and elevated BMI, but no obvious influence on the
      GH-IGF-I axis. Furthermore, it appeared that the males required twice the dose of
      antipsychotic compared with females.

PMID- 11318767
TI  - A randomized controlled assessment of the effects of different dosing regimens of
      budesonide on the HPA-axis in healthy subjects.
AB  - AIMS: To investigate the effect on the hypothalamo-pituitary-adrenal (HPA) axis
      of treatment with budesonide, 400 microg once daily, morning or evening, or 200
      microg twice daily, and 800 microg twice daily via Turbuhaler in a randomized,
      placebo-controlled, double-blind, double-dummy crossover study. METHODS: Healthy
      men received budesonide, 400 microg in the morning (08.00-09.00 h) or evening
      (20.00-21.00 h), budesonide, 200 microg twice daily, 800 microg twice daily, and
      placebo twice daily, for 1 week each. Plasma and urine samples were obtained over
      24 h on day 7 for cortisol determination. Twenty-five subjects completed all
      treatments, and 27 were included in the analysis. RESULTS: The 24 h plasma
      cortisol concentrations vs placebo (95% CI) were 98% (89, 108) for 400 microg in
      the morning, 92% (83, 100) for 400 microg in the evening, 95% (86, 104) for 200
      microg twice daily, and 76% (70, 84) for 800 microg twice daily. CONCLUSIONS:
      Budesonide at a dose of 400 microg day-1 via Turbuhaler had no statistically
      significant effect on 24 h cortisol production, irrespective of whether treatment
      is given once or twice daily, whereas a dose of 800 microg twice daily resulted
      in a statistically significant suppression vs placebo. Neither could a
      significant difference be found between morning and evening dosing.

PMID- 11318768
TI  - A placebo-controlled study examining the effect of allopurinol on heart rate
      variability and dysrhythmia counts in chronic heart failure.
AB  - AIMS: Allopurinol improves endothelial function in chronic heart failure by
      reducing oxidative stress. We wished to explore if such an effect would attenuate
      autonomic dysfunction in CHF in line with many other effective therapies in CHF.
      METHODS: We performed a prospective, randomized, double-blind cross-over study in
      16 patients with NYHA Class II-IV chronic heart failure (mean age 67 +/- 10
      years, 13 male, comparing allopurinol (2 months) at a daily dose of 300 mg (if
      creatinine < 150 micromol l-1) or 100 mg (if creatinine > 150 micromol l-1) with
      matched placebo. Mean heart rate and dysrhythmia counts were recorded from 24 h
      Holter tapes at monthly intervals for 6 months. We assessed autonomic function
      using standard time domain heart rate variability parameters (HRV): SDNN, SDANN,
      SDNN index, rMSSD and TI. RESULTS: Allopurinol had no significant effect on heart
      rate variability compared with placebo; the results are expressed as a difference
      in means +/- s.d. with 95% confidence interval (CI) between allopurinol and
      placebo: SDNN mean = 6.5 +/- 4.8 ms, P = 0.18 and 95% CI (-3.7, 17); TI mean = 
      2.1 +/- 1.4, P = 0.16 and 95% CI (-5.2, 0.8); SDANN mean = -2.8 +/- 7 ms, P =
      0.68 and 95% CI (-18, 12); SDNNi mean = 2 +/- 6.6, P = 0.7 and 95% CI (-12, 16);
      RMSSD mean = -0.9 +/- 2, P = 0.68 and 95% CI (-5.6, 3.7). For mean heart rate the
      corresponding results were 0.9 +/- 1.4, P = 0.5 and 95% CI (-2, 3.8). Log 24 h
      ventricular ectopic counts (VEC) were 0.032 +/- 0.37, P = 0.7 and 95% CI (-0.1,
      0.2). Patient compliance with study medication was good since allopurinol showed
      its expected effect of reducing plasma uric acid (P < 0.001). CONCLUSIONS:
      Allopurinol at doses, which are known to reduce oxidative stress appear to have
      no significant effect on resting autonomic tone, as indicated by time domain
      heart rate variability or on dysrhythmia count in stable heart failure patients.

PMID- 11318770
TI  - Drug expenditure in hospitals: what do German ward physicians know?
AB  - AIMS: Ward physicians hold key positions in the course of efforts to reduce drug
      expenditures in hospitals. This study evaluated the knowledge of German hospital
      physicians with respect to the daily therapeutic costs of 21 frequently used
      drugs. METHODS: A questionnaire survey was carried out among 168 ward physicians
      from university and municipal hospital departments of internal medicine. RESULTS:
      One hundred and twenty-seven physicians returned a completed questionnaire, a
      response rate of 75.6%. On average the physicians successfully identified both
      low cost and expensive drugs. The prices of inexpensive and moderately expensive
      drugs were generally overestimated whereas those for the expensive and highly
      expensive drugs were underestimated in 35% and 68% of respondents, respectively.
      CONCLUSIONS: The results of this survey of German hospital physicians suggest
      that a more economically efficient use of drugs could be achieved by an improved
      knowledge of daily therapeutic costs.

PMID- 11318769
TI  - A dose-response study of adrenaline combined with lignocaine 2%: effect on acute
      postoperative pain after oral soft tissue surgery.
AB  - AIMS: The combination of lignocaine and adrenaline may cause more postoperative
      pain than other types of local anaesthetic agents with comparable clinical
      efficacy. This study investigates the dose-response effect of adrenaline added to
      lignocaine on postoperative pain, when used as local anaesthetic for oral soft
      tissue surgery. METHODS: A controlled, randomized, double-blind, parallel group
      study included 195 patients (108 females/87 males) with mean age 49 years (range
      26-75 years). The patients were allocated to one of three treatment groups
      receiving lignocaine 2% (n = 66), lignocaine 2% with adrenaline 1 : 160 000 (n =
      63) or lignocaine 2% with adrenaline 1 : 80 000 (n = 66). RESULTS: Lignocaine 2%
      with adrenaline 1 : 80 000 gave significantly more pain intensity than lignocaine
      2% or lignocaine 2% with adrenaline 1 : 160 000. The postoperative pain intensity
      courses after lignocaine 2% and lignocaine 2% with adrenaline 1 : 160 000 showed
      a similar pattern except for the time period just after completion of surgery
      when lignocaine 2% with adrenaline 1 : 80 000 caused less pain. CONCLUSIONS: High
      adrenaline concentrations (1 : 80 000) combined with lignocaine local anaesthetic
      solution offers no advantage with respect to pain alleviation during the
      immediate postoperative pain period. High exogenous adrenaline concentrations may
      play a significant role in enhancing acute postoperative intensity.

PMID- 11318771
TI  - Carbamazepine is not a substrate for P-glycoprotein.
AB  - AIMS: To determine whether the anticonvulsant carbamazepine (CBZ), a known CYP3A4
      substrate, is also a substrate for the multidrug efflux transporter P
      glycoprotein (Pgp). METHODS: The role of Pgp in the transport of CBZ was assessed
      in three systems: (a) in mdr1a/1b(-/-) and wild-type mice after administration of
      2 mg kg-1 and 20 mg kg-1, which served as a model for brain penetration; (b) in
      Caco-2 cells, an in vitro model of the intestinal epithelium that is known to
      express high Pgp levels; and (c) by flow cytometry in lymphocytes using rhodamine
      123, a fluorescent substrate for PgP. RESULTS: Brain penetration of both doses of
      CBZ at 1 h and 4 h was comparable in wild-type and mdr1a/1b(-/-) mice. Transport
      across the Caco-2 cell monolayer was Pgp-independent, and was not affected by the
      Pgp inhibitor PSC-833. CBZ had no effect on rhodamine 123 efflux from
      lymphocytes, in contrast to verapamil, which increased fluorescence intensity
      fivefold. CONCLUSION: CBZ is not a substrate for Pgp. Its efficacy is unlikely to
      be affected by Pgp over-expression in the brain. Furthermore, the interaction of
      CBZ with drugs that modulate both CYP3A4 and Pgp function such as verapamil is
      probably due to inhibition of CYP3A4 and not Pgp.

PMID- 11318772
TI  - A single dose of methadone inhibits cytochrome P-4503A activity in healthy
      volunteers as assessed by the urinary cortisol ratio.
AB  - AIMS: To examine the effect of a single oral dose of methadone on cytochrome P450
      (CYP) 3A activity using the urinary 6beta-hydroxycortisol to cortisol ratio (UCR)
      as a marker of CYP3A activity. METHODS: A single oral dose (0.2 mg kg-1) of rac
      methadone was administered to eight healthy female volunteers. Frequent blood
      samples and all urine over seven time periods was collected for 96 h following
      dosing. The UCR and the concentration of the major CYP3A metabolite of methadone,
      EDDP, were measured in urine. Methadone enantiomer concentrations were determined
      in plasma and urine. All quantifications were performed by validated high
      performance liquid chromatography assays. RESULTS: In all volunteers a
      significant decline of the UCR from immediately predose values was observed at
      the 4-8 and 8-12 h collection periods (P < 0.05, 95% CI for the differences:
      0.4,16 and 0.6,16, respectively) with a return to immediately predose values
      after 2-3 days, suggesting methadone was an inhibitor of CYP3A. The UCR was found
      to be significantly correlated with the amount of EDDP excreted in the urine and
      with the area under the plasma concentration vs time profile for total (R + S)
      methadone, supporting in vitro data that CYP3A is primarily responsible for EDDP
      formation and has a significant influence on methadone disposition. CONCLUSIONS:
      Methadone appears to be a CYP3A inhibitor in vivo following a single oral dose
      and measurements of the urinary cortisol ratio appear to be a useful index to
      follow this inhibition.

PMID- 11318773
TI  - Effects of nociceptin and endomorphin 1 on the electrically stimulated human vas
      deferens.
AB  - AIMS: To examine the effects of nociceptin (NC) and endomorphin 1 (EM1) on
      electrical field stimulation (EFS)-induced contractions of the human vas deferens
      (hVD). METHODS: Concentration-response curves to NC and EM1 were constructed in
      the absence and in presence of peptidase inhibitors (PI). In some experiments a
      NC receptor antagonist, [Phe1psi(CH2-NH)Gly2]NC(1-13)NH2 [F/G], 10 microM) or
      naloxone (1 microM) were included. RESULTS: All data are mean(95%CI). In the
      presence of PI, NC inhibited twitches (Emax = 67(44,90)%; pEC50 =
      7.28(6.95,7.61)). NC inhibition was sensitive to [F/G]. EM1 also inhibited
      twitches both in the absence (Emax = 82(73,91)% pEC50 = 7.07(6.92,7.22)) and
      presence (Emax = 83(76,90)%; pEC50 = 7.00(6.91, 7.09)) of PI. EM1 inhibition was
      sensitive to naloxone. CONCLUSIONS: These data suggest that hVD express NC and
      opioid receptors that inhibit neurogenic contractions.

PMID- 11318774
TI  - Pharmacokinetics and systemic beta2-adrenoceptor-mediated responses to inhaled
      salbutamol.
AB  - AIMS: To examine whether systemic beta2-adrenoceptor responses, such as
      tachycardia, tremor and hypokalaemia, can be used as a surrogate for the 20 min
      pharmacokinetic profile of inhaled salbutamol. METHODS: A retrospective analysis
      of eight separate published studies in healthy volunteers was performed, each
      with an identical protocol evaluating the early lung absorption profile of a
      nominal 1200 microg dose of salbutamol given by different inhaler devices. Peak
      postural finger tremor, plasma potassium and heart rate were assessed. RESULTS:
      We found the maximum (Cmax) and average (Cav) plasma concentrations of salbutamol
      to be correlated (P < 0.0001) to change in plasma potassium (Cmax r = 0.904; Cav
      r = 0.899) and tremor (Cmax r = 0.875; Cav r = 0.857). No significant
      correlations existed between change in heart rate and Cmax (r = 0.425) or Cav (r
      = 0.415). CONCLUSIONS: Systemic beta2-adrenoceptor responses, in particular
      hypokalaemia and tremor, but not heart rate, appear to be good surrogates for
      evaluating the lung delivery of inhaled salbutamol. Consequently it is suggested
      that potassium or tremor responses may be used to evaluate the relative lung
      delivery of salbutamol from different inhaler devices.

PMID- 11318775
TI  - Orexins/hypocretins: waking up the scientific world.

PMID- 11318776
TI  - Clinical implications and management of oestrogen deficiency in the male.

PMID- 11318777
TI  - Autoimmune polyendocrinopathy syndrome type 1: treat with kid gloves.

PMID- 11318778
TI  - Effects of androgen deficiency and replacement on prostate zonal volumes.
AB  - BACKGROUND AND OBJECTIVES: Androgens play a key role in prostate development and
      disease. However the effects of androgen deficiency and replacement on the
      prostate during mid-life are not well understood, and there is no information on
      their effects on prostate zonal volumes. This study aimed to define the effects
      of androgen deficiency and androgen replacement therapy on prostate zonal volumes
      (central, peripheral & total) using planimetric prostate ultrasound with
      particular emphasis on the central zone of the prostate, the most hormonally
      sensitive and fastest growing region of the prostate and the zone where nodular
      benign prostate hyperplasia originates. PATIENTS AND MEASUREMENTS: Central and
      total prostate volume were measured directly, and peripheral prostate volume
      calculated, by a single observer using transrectal ultrasound in 71 hypogonadal
      men (aged 40 +/- 2, range 18-78 years) who were compared with individually age
      matched health controls without prostate or gonadal disease. Among the men with
      androgen deficiency, 17 men had untreated androgen deficiency (never treated or
      no treatment for at least 6 months) and 54 men were receiving long-term androgen
      replacement therapy (median 32 months, 93% > or = 6 months) with testosterone
      implants (n = 27), testosterone ester injections (n = 24) or other testosterone
      treatment (n = 3). RESULTS: Compared with individually age-matched controls,
      untreated androgen deficient men (n = 17) had reduced central (4.0 +/- 0.5 vs.
      6.2 +/- 0.5 ml, P < 0.001) and total (23.4 +/- 2.6 vs. 29.2 +/- 1.6 ml, P <
      0.001) prostate volumes whereas the reduction in peripheral prostate volume (19.4
      +/- 2.1 vs. 23.0 +/- 1.3 ml, P = 0.15) was not statistically significant. Men
      with treated androgen deficiency (n = 54) also still had significantly reduced
      central (4.8 +/- 0.4 vs. 6.8 +/- 0.4, P < 0.001), peripheral prostate volume
      (19.6 +/- 0.8 vs. 21.6 +/- 0.7 ml, P = 0.06) and total (24.4 +/- 1.1 vs. 28.4 +/-
      1.0 ml, P = 0.008) despite prolonged restoration of physiological testosterone
      concentrations. Neither modality of testosterone treatment nor type of
      hypogonadism influenced prostate zonal volumes before or after treatment. In
      contrast, central, peripheral and total prostate volume increased with age among
      healthy controls and men with androgen deficiency regardless of androgen
      replacement therapy. Plasma PSA concentrations were reduced in men with untreated
      androgen deficiency and were similar to age-matched controls in men with treated
      androgen deficiency. CONCLUSIONS: We conclude that, during mid-life, chronic
      androgen deficiency due to hypogonadism is associated with reduced central,
      peripheral and total prostate volumes. Reduced prostate volumes persist even
      during long-term maintenance of effective androgen replacement therapy with
      physiological testosterone concentrations until the fourth decade of life. After
      that, prostate volumes increase with age regardless of androgen deficiency or
      replacement. These findings suggest that, during mid-life, age is a more
      important determinant of prostate growth than ambient testosterone concentrations
      maintained in the physiological range. The persistently subnormal prostate
      volumes despite adequate androgen replacement therapy may explain the apparent
      paucity of cases of overt prostate disease among testosterone-treated androgen
      deficient men who retain protection against prostate disease despite
      physiological androgen replacement therapy.

PMID- 11318779
TI  - Lipids and lipoprotein subfractions in women with PCOS: relationship to metabolic
      and endocrine parameters.
AB  - OBJECTIVE: Women with polycystic ovary syndrome (PCOS) exhibit an abnormal
      lipoprotein profile, characterized by raised concentrations of plasma
      triglyceride, marginally elevated low density lipoprotein (LDL)-cholesterol, and
      reduced high density lipoprotein (HDL)-cholesterol. However, a normal LDL
      cholesterol level may be misleading since LDL exists as subpopulations of
      particles differing in size and atherogenic potential. Smaller LDL particles are
      more atherogenic and high concentrations often occur in association with elevated
      circulating triglyceride concentrations (but frequently normal total LDL
      cholesterol), increased hepatic lipase activity (HL) and insulin resistance.
      Information on LDL subclasses and HL activity in women with PCOS is sparse. The
      aim of this study was to determine the concentrations of small, dense LDL (LDL
      III) in women with PCOS relative to body mass index (BMI)-matched controls. We
      also examined the association of lipoprotein subfraction concentrations with
      endogenous sex hormone concentrations, since existing literature suggested that
      androgens up-regulate and oestrogens down-regulate HL activity, a key determinant
      of LDL subfraction distribution. DESIGN: Cross sectional study. PATIENTS: Fifty
      two women with oligomenorrhoea and polycystic ovaries determined by ultrasound
      and BMI matched women with normal menstrual rhythm (NMR) and normal ovarian
      appearances (n = 14) were recruited from gynaecology clinics. Anthropometric data
      and fasting blood samples were obtained for metabolic, hormonal and LDL
      subfraction estimation and a heparin provocation test was used to estimate HL
      activity. RESULTS: Subjects with PCOS demonstrated higher waist:hip ratio (WHR),
      testosterone, triglyceride, VLDL-cholesterol concentrations, and HL activity (P <
      0.05), whereas SHBG concentrations were significantly lower than controls. PCOS
      women had higher concentrations (38.0 vs. 25.0 mg/l; P = 0.026) and proportions
      (12.8 vs. 8.2%; P = 0.006) of small, dense LDL (LDL III), relative to controls.
      Within the PCOS group, plasma triglyceride and HL activity were the strongest
      univariate predictors of LDL III mass. They remained as independent predictors in
      multivariate analysis, and together accounted for 37% of its variability (P =
      0.0002). Independent predictors of plasma triglyceride and HL in turn, were
      measures of fat distribution (waist circumference or WHR) and fasting insulin
      concentration. Serum testosterone concentration was not associated either in
      univariate or multivariate analysis with any of the measured lipid, lipoprotein
      or subfraction parameters, nor with HL activity in the women with PCOS.
      CONCLUSION: We conclude that women with polycystic ovary syndrome have increased
      hepatic lipase activity and mass and percentage of small, dense low density
      lipoprotein relative to body mass index-matched controls with normal menstrual
      rhythm and normal ovaries. Further, these metabolic perturbances appear related
      more closely to adiposity/insulin metabolism than to circulating androgen levels.

PMID- 11318780
TI  - Smaller LDL particle size in women with polycystic ovary syndrome compared to
      controls.
AB  - OBJECTIVE: Women with polycystic ovary syndrome (PCOS) have an increased risk of
      cardiovascular disease. The contribution of lipid abnormalities to this higher
      risk, in particular atherogenic modifications of low density lipoprotein (LDL)
      such as a shift towards smaller LDL, has not been properly explored. We aimed to
      examine LDL size variation in relation to androgens and other risk factors in
      women with PCOS. DESIGN: Comparison of clinical and biochemical measurements in
      women with PCOS and women with normal ovarian function, of similar age and body
      mass index (BMI). PATIENTS: Thirty-one women with PCOS and 27 controls were
      studied. Patients were recruited from the outpatient endocrine clinic.
      MEASUREMENTS: Fasting total cholesterol, triglycerides (TG), high density
      lipoprotein (HDL), LDL, glucose, insulin, gonadotrophins, androgens, oestradiol,
      17 OH progesterone and SHBG were measured. LDL particle diameter was calculated
      based on distance travelled in polyacrylamide native gels. Recumbent blood
      pressure was measured automatically. RESULTS: LDL particle size appeared to be
      significantly smaller in hyperandrogenic PCOS as compared to regularly cycling
      women (P = 0006), independent of variations in lipid levels. SHBG was the only
      independent predictor of LDL size in this population, with a strong correlation,
      which persisted after adjustment for all confounding variables. CONCLUSIONS: Our
      results suggest that androgen excess and mild insulin-resistance (both
      responsible for lower SHBG) may have an early modifying effect on low density
      lipoprotein size in polycystic ovary syndrome women. The denser pattern observed
      in polycystic ovary syndrome women could by itself constitute a higher
      cardiovascular risk, even in the absence of overt dyslipidaemia, and contribute
      to the excess risk of cardiovascular disease reported in this syndrome.

PMID- 11318781
TI  - An audit of 500 subcutaneous glucagon stimulation tests to assess growth hormone
      and ACTH secretion in patients with hypothalamic-pituitary disease.
AB  - OBJECTIVE: The insulin tolerance test (ITT) is usually regarded as the 'gold
      standard' for the assessment of the hypothalamic-pituitary axis (growth hormone
      (GH) and ACTH) but must be used with caution and is contra-indicated in certain
      groups of patients. The glucagon stimulation test (GST) has previously been shown
      to be a good alternative when the ITT is contra-indicated and like the ITT
      stimulates both GH and ACTH secretion. There is however limited data on the use
      of the GST in patients with hypothalamic-pituitary disease. DESIGN AND PATIENTS:
      An audit of 500 GST was performed in 374 patients with hypothalamic-pituitary
      disease. Glucagon was administered via the subcutaneous route and bloods were
      taken at times 0 90 120 150 180 210 and 240 minutes. RESULTS: In the vast
      majority peak GH (84.4%) and cortisol (93%) responses occurred between 120 and
      180 minutes Little information was obtained from the 240 minute sample. The
      medical supervision required was minimal and the side-effects encountered during
      this test were mild; 20% of the tests were associated with nausea occasionally
      with vomiting sweating or headaches. Four patients fainted but recovered quickly.
      CONCLUSIONS: This large audit has shown that the glucose stimulation test is well
      tolerated and can easily be performed in an out-patient setting with minimal
      medical supervision. The 240 minute sample added little additional information
      and could be omitted.

PMID- 11318783
TI  - Serum alpha-subunit levels in patients with pituitary adenomas.
AB  - OBJECTIVE: We investigated preoperative and postoperative serum alpha-subunit
      levels and the alpha-subunit response to TRH in patients with various types of
      pituitary tumour and correlated the data with histological findings in order to
      clarify the significance of alpha-subunit measurement in pituitary adenomas.
      PATIENTS: We examined 59 patients with pituitary tumours (22 with GH cell
      adenomas, 30 with clinically nonfunctioning adenomas and seven with other
      tumours) treated at Toranomon Hospital between 1996 and 1998. RESULTS: The basal
      alpha-subunit level was supranormal in six out of 22 (27%) patients with a GH
      cell adenoma and in nine out of 30 (30%) patients with a nonfunctioning adenoma.
      A paradoxical alpha-subunit response to TRH was found in seven out of 22 (32%)
      patients with a GH cell adenoma. These seven patients also showed a paradoxical
      GH response to TRH administration. In addition, paradoxical response to TRH was
      found in eight out of 30 (27%) patients with a clinically nonfunctioning adenoma.
      In contrast, patients with other types of pituitary tumour showed neither a
      supranormal alpha-subunit level nor a paradoxical response to TRH. The
      supranormal alpha-subunit level and the abnormal response to TRH were normalized
      in both GH cell adenoma and nonfunctioning adenoma patients after successful
      surgery. Immunohistochemical studies showed alpha-subunit positive cells in 51%
      of GH cell adenomas or nonfunctioning adenomas and there was a good concordance
      with the serum alpha-subunit levels in both GH cell adenoma and nonfunctioning
      adenoma patients. CONCLUSIONS: These findings suggest that supranormal serum
      alpha-subunit levels are mainly due to hypersecretion by the tumour itself, while
      the paradoxical alpha-subunit response to TRH is an associated phenomenon in
      patients with a GH cell adenoma or nonfunctioning adenoma. The alpha-subunit
      level and the response to TRH may be useful indicators for assessing the
      operative outcome, especially in nonfunctioning adenoma patients who have no
      other definite endocrine markers.

PMID- 11318782
TI  - In vivo and in vitro effects of octreotide, quinagolide and cabergoline in four
      hyperprolactinaemic acromegalics: correlation with somatostatin and dopamine D2
      receptor scintigraphy.
AB  - OBJECTIVE: GH and PRL cosecretion frequently occurs in acromegaly and the
      sensitivity of both hormones to somatostatin analogs (SA) and dopamine agonists
      (DA) alone or in combination, is still debated. This study was designed to
      evaluate the in vivo and in vitro sensitivity to SA and/or DA and correlate the
      response in terms of hormone suppression to the results of in vivo somatostatin
      and dopamine receptor scintigraphy and to the immunohistochemical findings.
      DESIGN AND PATIENTS: Scintigraphy using 111In-DTPA-D-Phe(1)-OCT (111In-OCT) and
      123I-methoxybenzamide (123I-IBZM) was performed in four patients with acromegaly
      and high circulating GH, PRL and IGF-I levels. The results were correlated with
      the response to long-term treatment with octreotide (OCT), quinagolide (QN)
      and/or cabergoline (CAB), to the in vitro hormone suppression by OCT and DA in
      primary cultures from the pituitary tumors and to the immunohistochemical
      findings. RESULTS: The first patient showed high tumour uptake of 111In-OCT and
      123I-IBZM, the second high uptake of only 111In-OCT, while the third one showed
      faint tumour uptake of only 123I-IBZM, and the fourth a faint uptake of 111In
      OCT. In the first and in the fourth patients OCT or CAB administered alone failed
      to normalize hormone levels while the combined treatment induced circulating GH,
      IGF-I and PRL normalization. In the second patient OCT administered alone
      normalized hormone levels while QN reduced PRL levels only. In the third patient
      both OCT and QN, alone or in combination, failed to normalize hormone levels.
      However, in this patient GH and PRL suppression was significantly greater after
      QN than OCT treatment. After medical therapy, all the patients were operated on.
      Immunohistochemistry showed diffuse GH and focal PRL staining in the first
      patient, while diffuse GH and PRL staining in the remaining three. In vitro, OCT
      significantly suppressed GH secretion in the four primary pituitary tumor
      cultures, while PRL secretion was significantly suppressed only in the second and
      the fourth cases. Dopamine agonists (DA) significantly suppressed PRL release in
      all the cultures, while GH secretion was significantly suppressed in three out of
      four. CONCLUSIONS: These four acromegalics, presenting similar clinical findings
      and comparable peripheral hormone levels, showed different responsiveness to SA
      and DA. Moreover, during the in vitro study on primary tumor cell cultures, OCT
      and DA displayed an inhibiting activity on GH and PRL secretion positively
      correlated with the response observed in vivo. This evidence together with the in
      vivo receptor imaging study suggest the existence of somatostatin and/or dopamine
      D2 receptor heterogeneity in this class of pituitary tumors. The new potent DA
      might be primarily considered in the medical treatment of hyperprolactinemic
      acromegalics, while SA alone or in combination with DA in case of ineffective
      hormone suppression.

PMID- 11318784
TI  - In vitro secretion of FSH by cultured clinically nonfunctioning and gonadotroph
      pituitary adenomas is directly correlated with locally produced levels of activin
      A.
AB  - OBJECTIVE: Expression of mRNAs encoding activin and its antagonists inhibin and
      follistatin has been described in human pituitary adenomas, including clinically
      nonfunctioning adenomas (NFAs) and gonadotroph adenomas (Gn-omas). Since many of
      the NFAs and Gn-omas secrete FSH in vitro, we hypothesized that locally produced
      activin may stimulate secretion of FSH in these pituitary adenomas. PATIENTS AND
      METHODS: Pituitary adenoma tissue was obtained from 38 patients diagnosed
      preoperatively as having NFAs (n = 17), Gn-omas (n = 5), prolactinomas (n = 6) or
      growth hormone (GH)-producing adenomas (n = 10). Actual protein levels of
      activin, inhibin, follistatin, FSH and LH were measured in media of these 38
      cultured pituitary adenomas. In addition, we investigated correlations between
      concentrations of these growth factors and hormones in NFAs and Gn-omas. RESULTS:
      Gn-omas were found to secrete significantly more activin A in their culture
      medium than PRL- and GH-producing adenomas (P < 0.05). Inhibin A and inhibin B
      protein levels in culture media were very low. A positive correlation between
      levels of activin A and FSH (r = 0.56, P < 0.005) was found, while no correlation
      between activin A and LH could be detected. Furthermore, levels of follistatin
      were positively correlated with activin A levels (r = 0.73, P < 0.0005).
      Comparison of the activin A:follistatin ratio with the measured FSH protein
      levels showed an even stronger relationship (r = 0.79, P < 0.0005). CONCLUSIONS:
      It is concluded that levels of activin A, follistatin and FSH in media of
      cultured nonfunctioning adenomas and gonadotroph adenomas are positively
      correlated. This suggests that these adenomas secrete FSH in response to the
      relatively high locally produced levels of activin A.

PMID- 11318785
TI  - A novel homozygous mutation in the second transmembrane domain of the
      gonadotrophin releasing hormone receptor gene.
AB  - BACKGROUND AND OBJECTIVE: Mutations in the GnRH receptor (GnRH-R) gene cause
      hypogonadotrophic hypogonadism. Here, we present the molecular studies of the
      GnRH-R gene in three families with isolated hypogonadotrophic hypogonadism.
      PATIENTS: Three unrelated families, with at least two members diagnosed with
      isolated hypogonadotrophic hypogonadism were included. MEASUREMENTS: DNA
      sequencing was performed after polymerase chain reaction amplification of each of
      the three exons of the gene. RESULTS: A novel homozygous missense mutation, at
      nucleotide 268, turning glutamic acid into lysine, located at the second
      transmembrane domain of the GnRH-R gene was found in two patients pertaining to
      one of the families studied. Both parents and an unaffected brother were
      heterozygous carriers of one mutant allele, an unaffected sister was homozygote
      wild type. In the other two affected families no mutations were found in the GnRH
      R gene. CONCLUSIONS: This constitutes the first description of an spontaneous
      mutation located at the second transmembrane domain (Glu90Lys) of the GnRH-R,
      indicating that the integrity of glutamic acid at this position is crucial for
      receptor function. Also this report, complementing others, demonstrates that
      mutations are distributed throughout the GnRH-R gene and that as in the only
      other homozygous mutation previously described, affected patients present a
      complete form of hypogonadotrophic hypogonadism. Due to the fact that apparently
      consanguinity was present in our affected family, we presume that the mutation
      derived from a common ancestor, by a founder gene effect.

PMID- 11318786
TI  - Increased levels of insulin-like growth factor binding protein-2 in sera and
      tumours from patients with colonic neoplasia with and without acromegaly.
AB  - OBJECTIVE: Patients with acromegaly are at increased risk of developing
      colorectal carcinoma and premalignant tubulovillous adenoma. The pathogenesis of
      these neoplasms could involve a stimulatory effect of serum growth factors on
      colonic epithelial cell proliferation. The aim of this study was to evaluate
      changes in (1) serum IGF-I, IGF-II, IGFBP-3 and IGFBP-2 and (2) changes in local
      expression of IGFBPs and p53 in colonic epithelium in patients with colonic
      neoplasia with and without acromegaly. DESIGN: A cross-sectional retrospective
      study was performed. Fasting serum samples were obtained at the time of
      colonoscopy for patients with acromegaly and at the time of surgery for patients
      with colonic neoplasia without acromegaly. MEASUREMENTS: Serum IGF-I, IGF-II,
      IGFBP-2 and IGFBP-3 were measured using specific immunoassays. Tissue expression
      of IGFBP-2, IGFBP-3 and p53 status were determined by immunohistochemistry.
      PATIENTS: Group 1: 26 age- and sex-matched control subjects (range 40-69 years);
      group 2: 18 patients with acromegaly without colonic neoplasia (range 39-68
      years); group 3: 18 patients with acromegaly and colonic neoplasia (range 41-74
      years, 11 = adenoma, seven = carcinoma); group 4: 19 patients with colonic
      neoplasia without endocrine disease (range 43-91 years, four = adenoma, 15 =
      carcinoma). Immunohistochemical staining of colonic biopsies was performed for
      IGFBP-2, IGFBP-3 and p53 in groups 3 and 4. RESULTS: Mean serum IGF-I and IGFBP-3
      levels were significantly elevated in group 2 (371 +/- 131 microg/l and 6.5 +/-
      1.8 mg/l, respectively) and group 3 (379 +/- 174 microg/l and 5.8 +/- 1.6 mg/l,
      respectively), and significantly reduced in group 4 (103 +/- 36 microg/l and 2.4
      +/- 1 mg/l) compared to controls (165 +/- 40 microg/l and 4.7 +/- 1 mg/l; P <
      0.0001, P < 0.001, respectively). However, median serum IGFBP-2 levels were
      significantly elevated in group 3 (P < 0.01) and group 4 (P < 0.0001).
      Immunostaining for IGFBP-2 showed strong areas of immunoreactivity in the
      cytoplasm of malignant colonic epithelium compared to benign epithelium. IGFBP-3
      immunostaining showed strong areas of immunoreactivity in the cytoplasm and in
      the nucleus of malignant and benign colonic epithelium compared to the normal
      epithelium. Nuclear staining for p53 was observed in three patients from group 3
      (two carcinoma, one adenoma) and four patients from group 4 (all carcinoma).
      CONCLUSION: Our results describe changes in IGFBP-2 expression in colonic
      neoplasia in patients with and without acromegaly, which suggest that this
      binding protein may regulate local bioavailability of IGF, which in turn could
      modulate colonic cell proliferation and/or differentiation.

PMID- 11318787
TI  - Effect of acute pharmacological modulation of plasma free fatty acids on GH
      secretion in acromegalic patients.
AB  - OBJECTIVES: In acromegaly GH secretion is markedly increased due in most cases to
      a GH secreting pituitary adenoma. GH secretion is modulated by variations in the
      levels of free fatty acids (FFA). Recent studies in different clinical
      situations, have shown that reduction in FFA with acipimox (A) modifies
      somatotroph cell responsiveness. The aim of the present study was to evaluate the
      effect of acute pharmacological reduction of plasma FFA on both basal GH levels
      and GHRH-mediated GH secretion in acromegalic patients. PATIENTS: Six acromegalic
      patients (four female, two male) aged 57 +/- 4 years., with active disease due to
      pituitary adenomas were studied. Four of the patients had been treated previously
      by surgery and/or radiotherapy. The diagnosis of active acromegaly was
      established by clinical assessment, increased serum IGF-I and impaired GH
      suppression after oral glucose. MEASUREMENTS: Four tests were performed: placebo,
      A (250 mg, orally, - 210 minutes and - 60 minutes), GHRH (100 microg, iv, 0
      minutes) and GHRH plus A. The different tests on each subject were performed in
      random order one week apart, each subject served as their own control. Serum GH
      was measured by RIA at appropriate intervals. The area under the curve (AUC) was
      calculated by the trapezoidal METHOD: Statistical analysis was performed by
      Wilcoxon test. P < 0.05 was considered significant. RESULTS: The administration
      of A induced a FFA reduction during the entire test both when administered with
      placebo and with GHRH: AUC (mmol/l x 90 minutes): placebo plus placebo: 88.2 +/-
      7.3. Placebo plus A: 23.2 +/- 4.6 (P < 0.05). Placebo plus GHRH: 85.4 +/- 6.9. A
      plus GHRH: 21.8 +/- 3.8 (P < 0.05). Mean peak GH level (microg/l) after placebo
      plus placebo was 5.0 +/- 1.8 not significantly different than after placebo plus
      A with a mean peak of 6.2 +/- 2 (P = ns). Mean peak GHRH-induced GH secretion was
      26.0 +/- 15.4 and was not modified by previous A administration with mean peak of
      24.4 +/- 11.8 (P = ns). CONCLUSIONS: In acromegalic patients acute
      pharmacological reduction of FFA with acipimox did not modify basal GH levels or
      GHRH-induced GH secretion, suggesting that the adenomatous somatotroph cell is
      unresponsive to physiological signals such as FFA which act at a pituitary level.
      These data support the hypothesis of an intrinsic neoplastic pituitary defect for
      the pathogenesis of acromegaly.

PMID- 11318788
TI  - Increased arterial intima-media thickness by B-M mode echodoppler ultrasonography
      in acromegaly.
AB  - BACKGROUND: Patients with acromegaly have an increased morbidity and mortality
      for cardiovascular diseases. Despite the increasing evidence for the existence of
      a specific cardiomyopathy in acromegaly, the presence of vascular abnormalities
      has been never investigated. OBJECTIVE: To evaluate the cardiovascular risk and
      premature atherosclerosis in acromegaly. SUBJECTS: Forty-five patients with
      acromegaly and 30 sex- and age-matched healthy subjects were included in this
      study: 30 patients were studied at the diagnosis of acromegaly and were in active
      disease (GH 59.3 +/- 10.2 mU/l, IGF-I 733 +/- 57.6 microg/l) while 15 patients
      were studied after surgery and/or radiotherapy and were cured from the disease
      (GH 4.5 +/- 0.7 mU/l, IGF-I 172.4 +/- 16.9 microg/l). METHODS: Body mass index
      (BMI), systolic (SBP) and diastolic blood pressure (DBP), serum total, LDL- and
      HDL-cholesterol, triglycerides, and fibrinogen levels, prothrombin time (PT),
      activated partial thromboplastin time (APTT), glucose and insulin levels (fasting
      and after glucose load) were measured in all patients and controls. By
      echodoppler ultrasonography, blood systolic (SPV) and diastolic (DPV) peak
      velocity, and resistance index (RI) were measured at both common and internal
      carotid arteries where presence, size and location of atherosclerotic plaques
      were evaluated by B-Mode ultrasonography. Intima-media thickness (IMT) of both
      common carotids was measured by M-Mode ultrasonography. RESULTS: SBP, but not
      DBP, was significantly higher in patients with active disease than in cured
      patients and controls (P = 0.003). Hypertension was found in nine (30%) patients
      with active disease, in two (13.3%) of those cured from acromegaly and in none of
      controls (chi2 = 10.81, P < 0.004). Fasting blood glucose levels were
      significantly higher both in patients with active disease and in those cured from
      the disease than in controls (P < 0.001). Circulating insulin levels were
      significantly higher in patients with active disease than in cured patients and
      controls (P < 0.001) and in cured patients than in controls (P < 0.001). Glucose
      tolerance abnormalities were found in 13 (43.3%) patients with active disease, in
      four (26.6%) patients with inactive disease and in four controls (13.3%) (chi2 =
      6.71, P = 0.03). Total blood cholesterol levels were similar in the three groups,
      LDL-cholesterol and triglycerides levels were significantly higher, whereas HDL
      cholesterol levels were significantly lower both in patients with active disease
      and in those cured from the disease than in controls (P < 0.001). Serum
      fibrinogen levels were significantly higher both in patients with active disease
      and in those cured from the disease than in controls (P < 0.001). No difference
      was found in PT and APTT levels among the three groups. At the level of right and
      left common carotid arteries, IMT was significantly higher both in patients with
      active disease and in those cured from the disease than in controls (P < 0.001).
      Both right and left SPV, but not DPV, were significantly higher in patients with
      active disease than in those cured from the disease and in controls (P < 0.01).
      Well defined carotid wall plaques were detected in two patients (6.6%) with
      active disease, in one patient cured from the disease (6.6%) and in two controls
      (6.6%). At the level of right and left internal carotid arteries, SPV, DPV and RI
      were similar among the three groups. Well defined carotid wall plaques were
      detected in three patients with active disease (10%), two patients cured from the
      disease (13.3%) and in one control (3.3%). CONCLUSIONS: A significant increase of
      IMT of both common carotid arteries was observed in patients with active
      acromegaly, this was also found in those cured from acromegaly. However, the
      prevalence of well defined carotid plaques was not increased in both groups of
      patients with acromegaly as compared to controls. On this basis, heart more than
      vessels seems to be affected by chronic GH and IGF-I excess in acromegaly.

PMID- 11318789
TI  - The influence of gender on the short and long-term effects of growth hormone
      replacement on bone metabolism and bone mineral density in hypopituitary adults:
      a 5-year study.
AB  - OBJECTIVES: The objectives of this study were to investigate the effects of GH
      replacement therapy in hypopituitary adults with growth hormone deficiency (GHD)
      on activation of bone remodelling during dose titration and on BMD over a median
      of 58 months of continuous therapy. STUDY DESIGN: Open label study in adult
      patients with GHD. rhGH was commenced at dose of 0.8 IU subcutaneously daily (0.4
      IU if hypertensive or glucose tolerance impaired) with subsequent dose titration
      based on 2 weekly measurement of serum IGF-I until levels reached the target
      range (between the median and upper end of the age related reference range). In
      patients previously commenced on GH using weight based regimens the dose of GH
      was adjusted during clinical follow-up in order to maintain serum IGF-I in the
      target range. PATIENTS: Initial effects of GH on bone remodelling during dose
      titration were studied in 17 patients (8F). Long-term effects of GH were
      determined in a separate group of 13 GHD adults (6F) over a median period of 58
      months (range 44-72). MEASUREMENTS: Osteoblastic activity was estimated by
      measuring serum bone specific alkaline phosphatase (S-BAP). BMD was determined at
      both lumbar spine (L2-L4) and femoral neck by dual energy X-ray absorptiometry
      (DEXA). RESULTS: During dose titration a significant increment in S-BAP was
      observed by 10 weeks in females but occurred later in males (12-26 weeks). In the
      long term treatment group there was a significant increment in S-BAP compared to
      baseline (P = 0.013) after 6 months GH treatment. After long-term GH treatment
      (median 58 months) S-BAP levels decreased and were no longer statistically
      significantly different from baseline at the end of the study period. A similar
      response was observed in male and female patients. There were no significant
      differences in baseline BMD between male and female patients at either lumbar
      spine or femoral neck in the long term treatment group. No significant changes
      were observed in BMD after 6 months GH treatment in either lumbar spine or
      femoral neck but BMD increased over the remainder of the study at both sites (P =
      0.023 and P = 0.03 respectively). When analysed by gender male patients showed a
      clear positive change in BMD after longer-term replacement in both lumbar spine
      and femoral neck (P = 0.01 and P = 0.02 respectively) but female patients showed
      no significant changes. Qualitatively similar results were observed when
      analysing changes in BMD expressed as Z scores. CONCLUSION: This study
      demonstrates an earlier onset of GH activation of bone remodelling as reflected
      by S-BAP in females compared to males and confirms that long-term GH treatment in
      hypopituitary adults with GH deficiency increases or preserves BMD both at lumbar
      spine and femoral neck. However male patients seem to derive the greater benefits
      in BMD from long-term GH replacement; in females BMD appears simply to be
      stabilized rather than increased. This constitutes a genuine gender difference in
      susceptibility given that serum IGF-I was in the upper part of the reference
      range in all subjects.

PMID- 11318790
TI  - Effects of insulin and glucocorticoids on the leptin system are mediated through
      free leptin.
AB  - OBJECTIVE: Insulin and glucocorticoids are known to increase total leptin levels.
      However, the effects of insulin and glucocorticoids on the components of the
      leptin system - free leptin (FL), bound leptin (BL) and soluble leptin receptor
      (SR) - have not been elucidated. The aim of this study was to determine if there
      is a differential effect of insulin and glucocorticoids on the leptin system.
      MATERIAL AND METHODS: In the first of two studies (study 1), we measured free
      leptin (FL), bound leptin (BL), a soluble leptin receptor (SR) and insulin, by
      specific RIA methods, in six healthy subjects on a control day, and subsequently
      during a hyperinsulinaemic euglycaemic clamp study. In the second study (study 2)
      we measured the same parameters in six healthy subjects, before (day 1) and
      during administration of dexamethasone over 3 consecutive days. RESULTS: In study
      1, on the control day FL levels rose over the 16 h monitoring period (P = 0.057)
      and SR levels declined (P < 0.001), but there was no change of BL levels. Even
      after accounting for diurnal variation, FL levels increased even more
      substantially over 12 h of insulin infusion than observed on the control day (P <
      0.001). In study 2, mean FL concentration doubled from day 1 to day 2 (P = 0.01)
      and remained elevated subsequently. In contrast to FL, BL and SR levels remained
      unchanged during the study. Fasting insulin levels (pmol/l) increased from day 1
      to day 2, but this rise only approached significance on day 4 (P = 0.05).
      CONCLUSION: We conclude that insulin and dexamethasone increase free leptin
      levels, but do not change the concentrations of bound leptin and soluble leptin
      receptor. Furthermore, the dexamethasone-induced rise in leptin levels is (at
      least partially) independent of the effects of glucocorticoid-induced
      hyperinsulinaemia.

PMID- 11318791
TI  - The islet amyloid polypeptide (amylin) gene S20G mutation in Chinese subjects:
      evidence for associations with type 2 diabetes and cholesterol levels.
AB  - BACKGROUND AND OBJECTIVES: There has been evidence that the S20G mutation in the
      islet amyloid polypeptide (amylin) gene may be associated with type 2 diabetes.
      In the present study, we investigated the distribution of the mutation in Hong
      Kong Chinese, and examined whether there was evidence for associations between
      the mutation and type 2 diabetes and/or metabolic profiles. SUBJECTS AND METHODS:
      This study involved 227 early and 235 late-onset (defined as onset age < or = 40
      and > 40 years, respectively) type 2 diabetic patients, as well as 126
      nondiabetic subjects. The mutation was detected using a PCR-RFLP method. RESULTS:
      We identified six (2.6%) and one (0.4%) patients heterozygous for the mutation
      from the early and late-onset groups, respectively (P = 0.05). None of the
      nondiabetic subjects had the mutation. Insulin deficiency and poor glycaemic
      control were not common findings amongst carriers of the mutation. In the early
      onset group, the patients with the mutation had lower plasma levels of total (4.3
      +/- 0.9 mmol/l vs. 5.3 +/- 1.1 mmol/l, P = 0.02) and low density lipoprotein
      (LDL)-cholesterol (2.3 +/- 0.7 mmol/l vs. 3.2 +/- 0.9 mmol/l, P = 0.01) than
      those without the mutation. CONCLUSIONS: Our data suggest that the islet amyloid
      polypeptide gene mutation might be associated with early occurrence of type 2
      diabetes and lower plasma levels of total and low density lipoprotein-cholesterol
      in the Chinese population.

PMID- 11318792
TI  - Increasing incidence of childhood Graves' disease in Hong Kong: a follow-up
      study.
AB  - OBJECTIVE: Childhood Graves' disease has been reported to be rare but preliminary
      epidemiological data on its incidence appeared to be high in Hong Kong Chinese
      children. The aim of this study is to determine the incidence of childhood
      Graves' disease in Hong Kong and to analyse whether there is an increasing trend
      of the incidence. PATIENTS AND DESIGN: We established a registry of childhood
      Graves' disease at our centre to collect cases from four districts in Hong Kong.
      The diagnosis of Graves' disease was based on clinical features, diffused
      enlargement of thyroid gland, raised free thyroxine or triiodothyronine levels,
      suppressed TSH levels, and the presence of thyroid receptor antibodies. Confirmed
      cases of Graves' disease who resided in any of the four districts were used to
      calculate the incidence for the study period between 1989 and 1998. RESULTS: One
      hundred and eighteen Chinese children under 15 years of age had a confirmed
      diagnosis of Graves' disease during the study period from January 1989 to
      December 1998. There were 11 boys and 107 girls giving a male to female ratio of
      1 : 9.7. The overall incidence rates were 3.2/100 000/year and 6.5/100 000/year
      for the two periods 1989-93 and 1994-98, respectively. The incidence rates for
      girls have increased significantly (P < 0.001) from 3.8/100 000/year in 1989 to
      14.1/100 000/year in 1998. The current incidence of childhood Graves' disease in
      our population is about eight times that reported in Danish children.
      CONCLUSIONS: This study confirms the high incidence of childhood Graves' disease
      in Hong Kong and documents an increasing trend for girls. Further studies are
      required to reveal possible genetic or environmental factors responsible for such
      epidemiology in Hong Kong Chinese children.

PMID- 11318793
TI  - Oncogenic osteomalacia associated with mesenchymal tumour detected by indium-111
      octreotide scintigraphy.
AB  - In a 40-year-old man who had suffered from vague and generalized bone pains for 7
      years due to oncogenic osteomalacia, the causative tumour was finally detected by
      Indium-111 octreotide scintigraphy. Some characteristics of the tumour associated
      with oncogenic osteomalacia, such as its size, growth rate, location and origin,
      often make the diagnosis difficult. However, the recent discovery of somatostatin
      receptors in mesenchymal tumours, which are the most common cause of oncogenic
      osteomalacia, has raised the possibility of early detection of this devastating
      disorder. Here, we report that radiolabelled octreotide scintigraphy has a
      potential role as a diagnostic tool in oncogenic osteomalacia. However, the exact
      role of somatostatin receptors in tumours associated with oncogenic osteomalacia
      still remains elusive.

PMID- 11318794
TI  - Elevated inferior petrosal sinus levels of PTHrP in a patient with Cushing's
      disease.
AB  - PTHrP has been found in various tissues, including prolactinomas and growth
      hormone producing adenomas. The function and clinical importance of PTHrP are
      poorly understood. We report the case of a 25-year-old female patient with
      hirsutism. Autonomous ACTH-dependent hypercortisolism was documented by endocrine
      testing. Magnetic resonance imaging (MRI) revealed a 3-mm intrasellar hypointense
      lesion in the left side of the pituitary gland. The inferior petrosal sinus
      sampling disclosed a gradient of ACTH left central/peripheral of 30.5 and right
      central/peripheral of 2.0 and suggested the diagnosis of a left-sided pituitary
      ACTH secreting microadenoma. Interestingly, we found elevated PTHrP levels in the
      left inferior petrosal sinus with a gradient of 4.7 compared to peripheral venous
      blood and of 3.6 compared to the right sinus. Our results fit very well to the
      concept of a para-/autocrine secretion of PTHrP which has been proposed recently
      and suggest a role in the regulation of cell growth of pituitary adenomas.

PMID- 11318796
TI  - Haemophilias: advances towards genetic engineering replacement therapy.
AB  - Both haemophilia A and B are X-linked recessive disorders and therefore occur
      almost exclusively in males. The genes for both factors VIII and IX have been
      mapped to the distal end of the long arm of the X chromosome, bands Xq28 and
      Xq27.1, respectively. The Factor VIII gene comprises 186 kb DNA with 9 kb of exon
      of DNA which encodes an mRNA of nearly 9 kb. The Factor IX gene is 34 kb in
      length and the essential genetic information is present in eight exons which
      encode 1.6 kb mRNA. In gene therapy, genetic modification of the target cells can
      be either ex vivo or in vivo. The advantage of the ex vivo approach is that the
      genetic modification is strictly limited to the isolated cells. In the in vivo
      approach, the integrity of the target tissue is maintained but the major
      challenge is to deliver the gene to the target tissue. The use of improved
      retroviral and adenovirus-based vectors for gene therapy has produced clinically
      relevant levels of human factor VIII in mice and haemophilic dogs. If further
      improvements can increase the persistence of expression and decrease the
      immunological responses, phase I clinical trials in patients can be considered.

PMID- 11318795
TI  - Management of a pregnant patient with Graves' disease complicated by thionamide
      induced neutropenia in the first trimester.
AB  - A 31-year-old woman presented with neutropenia due to thionamide drug therapy for
      Graves' disease. She also reported 8 weeks of amenorrhoea and had a positive
      pregnancy test. Her drug therapy was discontinued and her neutropenia resolved
      uneventfully. The hyperthyroidism recurred a week later. After consideration of
      all treatment options, it was decided to observe until 14 weeks when an elective
      thyroidectomy was planned. Mother and fetus were monitored closely and both
      tolerated moderate hyperthyroidism well. At 14 weeks the patient underwent a
      total thyroidectomy after rendering her euthyroid with a short course of sodium
      ipodate. Labour was induced at 41 weeks. Delivery was complicated by fetal
      distress and precipitated a forceps delivery. A 3250 g male infant was born with
      poor Apgar score and required 2 h of ventilation. At 1 year, the child had
      reached all developmental milestones at appropriate times. Both mother and fetus
      may tolerate moderate thyrotoxicosis well in early pregnancy, an alternative that
      should be considered when thionamide drug therapy is contraindicated.

PMID- 11318797
TI  - Detection of massive transplacental haemorrhage by flow cytometry.
AB  - Flow cytometry has been shown to be a more accurate and sensitive method than the
      Kleihauer-Betke test for the measurement of feto-maternal haemorrhage in Rh(D)
      incompatibility. This report describes the successful use of flow cytometry to
      detect and monitor the management of a massive transplacental haemorrhage (105
      ml) of fetal Rh(D) positive cells in a Rh(D) negative woman. The report
      highlights the accuracy and reproducibility of the test and the stability of a
      blood sample when transferred 596 kilometres to a central testing facility.

PMID- 11318798
TI  - Coinheritance of two alpha-spectrin gene defects in a recessive spherocytosis
      family.
AB  - We studied a recessive hereditary spherocytosis (HS) family from Norway in which
      all four children had haemolytic spherocytosis while spectrin (Sp) deficiency was
      detected in the proband. Molecular analysis demonstrated that all affected
      children had inherited the low expression alpha-Sp allele LEPRA (Low Expressed
      PRAgue) from the father. Haplotyping with a polymorphic dinucleotide repeat for
      the alpha-Sp gene (alphaVNTR) located in the 3' untranslated region of mRNA
      showed that all recessive children had inherited the same maternal alpha-spectrin
      allele. The paternal Sp-alphaLEPRA allele was found in cis of the polymorphic
      alpha-Sp Bughill allele (alphaBH) characterized by the A970D point mutation in
      the Sp alpha-chain. This mutation was identified on two-dimensional
      electrophoresis of Sp tryptic digests as an acidic shift of the alphaII tryptic
      domains (spots alphaIIa). Analyses of the relative expression of the paternal
      alpha-Sp Bughill polymorphism in the proband showed that the product of the
      maternal alpha-Sp gene is almost completely absent from the mature erythrocyte
      membrane. Comparative analysis between alphaVNTR PCR-amplified from genomic DNA
      and from cDNA showed that the maternal low expression alpha-Sp allele is
      associated with a decreased amount of mRNA. Results from molecular and
      biochemical studies showed that all the affected children of this family are
      compound heterozygous for two different low expression alpha-Sp alleles: an
      uncharacterized defective alpha-Sp allele on the maternal side and an alphaLEPRA
      allele tagged by the alphaIIa polymorphism on the paternal side.

PMID- 11318799
TI  - Cold haemagglutinin disease: clinical significance of serum haemolysins.
AB  - Two hundred and twenty-one patients with cold haemagglutinins of thermal
      amplitude > or = 30 degrees C (considered to be a reasonable indicator of
      clinical significance) were classified by in vitro haemolysin activity into three
      groups. Group 1 contained 116 individuals in whom haemolysins were never
      detected; the 74 patients in Group 2 had monophasic haemolysins alone; whereas
      both monophasic and biphasic haemolysins were detected in the 31 Group 3
      patients. There was a significantly higher proportion of patients in Groups 2 and
      3 with haptoglobin levels < 0.1 g/l compared with Groups 1 and 2, respectively (P
      < 0.005 and P < 0.001). Direct antiglobulin test results showed that the
      autoimmune response became more complex and IgM predominant through Groups 1-3,
      resulting in an increasing ability to activate complement which was reflected in
      increasing haemolysin activity and number of patients with active haemolysis. The
      31 patients in Group 3 were mostly elderly (median age 71 years at presentation)
      and the majority had chronic cold haemagglutinin disease (CHAD), several in
      association with lymphoid neoplasms or carcinomas; only four had acute CHAD. The
      natural history of idiopathic chronic CHAD was of mild, well compensated
      haemolysis, punctuated by severe acute episodes necessitating intensive therapy.
      The condition often remained active for long periods and did not appear to affect
      natural lifespan. In some cases, no treatment (or just warmth) was needed; in
      others continuous or intermittent prednisolone and/or chlorambucil were
      effective; yet others required a greater variety and more intense therapy, or
      treatment of associated conditions. Blood transfusion support was frequently
      required when haemolysis was severe.

PMID- 11318800
TI  - New quantitative parameters on a recently introduced automated blood cell counter
      -the XE 2100.
AB  - The XE 2100 (Sysmex Corporation) is a cell counter that furthers the technology
      of fluorescent flow cytometry developed from the earlier range of Sysmex
      analysers. The new diagnostic features are a nucleated red cell count (NRBC), the
      ability to measure platelets by impedance as well as an 'optical' platelet count
      using a fluorescence dye and an immature granulocyte (IG) count. The NRBC count
      was highly correlated (r = 0.97) with the manual reference count. For counts
      below 100 x 109/l the 'optical' method and the immunocount gave good a
      correlation (r = 0.97) optical and impedance counts were also well correlated (r
      = 0.89). The use of the 'optical' platelet count significantly improves the
      reliability of low platelet counts. The IG count correlated with visual counts (r
      = 0.81) and allows the detection of immature cells at an earlier stage in the
      laboratory process. The introduction of fluorescent flow cytometric analysis
      allows extended quantification of additional cell populations and so potentially
      improves screening and monitoring of various pathological conditions.

PMID- 11318801
TI  - Evaluation of a global screening assay for the investigation of the protein C
      anticoagulant pathway.
AB  - We have evaluated a global screening test for the protein C pathway, the 'ProC
      Global' (Dade Behring Ltd, Milton Keynes, UK). Patient groups tested included
      inherited protein C or S deficient and inherited/acquired activated protein C
      resistance. Results showed that protein C deficiencies and activated protein C
      resistance could be successfully detected with this test whereas deficiencies of
      protein S were less readily distinguished from the normal population. The ProC
      Global was unreliable in patients with antiphospholipid antibodies, raised plasma
      factor VIII:C and in those receiving oral anticoagulant therapy.

PMID- 11318802
TI  - The management of isolated thrombocytopenia in Chinese adults: does bone marrow
      examination have a role at presentation?
AB  - We performed a retrospective analysis of bone marrow examination (BME) in the
      management of Chinese adult patients less than 60 years of age with isolated
      thrombocytopenia at presentation. Eighty-three patients with a median age of 39
      years presenting with isolated thrombocytopenia (median platelet count: 38 x
      10(9)/l) had routinely undergone BME as part of the laboratory investigations
      during the period from January 1996 to December 1999. All 83 patients had bone
      marrow findings of active marrow suggesting causes due to peripheral destruction.
      All of these patients responded to steroid or intravenous immunoglobulin (IVIg)
      therapy at presentation if their platelet counts were significantly low or if
      they had mucosal bleeding. Eighty-one of the 83 patients, after a median of 20
      months follow-up, were finally diagnosed as having idiopathic thrombocytopenic
      purpura (ITP). The remaining two patients were finally confirmed as cases of
      systemic lupus erythematosus (SLE). Our results suggest that BME is not helpful
      in the diagnosis of isolated thrombocytopenia or suspected ITP in adult patients
      at presentation, provided that a thorough clinical history and physical
      examination are undertaken and that the blood count and peripheral blood smear
      show no abnormalities apart from the thrombocytopenia.

PMID- 11318803
TI  - Flow cytometry analysis of platelet P-selectin expression in whole blood-
      methodological considerations.
AB  - P-selectin is an adhesion molecule found in the alpha granules of platelets.
      Activation occurs in response to a range of inflammatory and thrombotic agents
      resulting in rapid up-regulation. Flow cytometry methods have recently been
      described for the analysis of platelet P-selectin expression in whole blood.
      While introducing these methods into our laboratory it was noted that expression
      could be stimulated, in vitro, in a number of ways. This study shows that red
      cell lysis, the anticoagulant K3 EDTA and the time elapse between blood
      collection and antibody labelling had statistically significant effects on P
      selectin expression. Post-labelling fixation, with CellFIX, caused no significant
      effect. We conclude that blood for P-selectin analysis should be collected in
      sodium citrate and that red cell lysis and centrifugation should be avoided. When
      comparing samples, the time between collection and labelling should be
      standardized. The relatively high CV for the assay indicates that all samples
      should be labelled and analysed in duplicate with the mean level reported.

PMID- 11318804
TI  - Direct antiglobulin test negative, non spherocytic autoimmune haemolytic anaemia.
AB  - We report a case of direct antiglobulin test (DAT) negative warm autoimmune
      haemolytic anaemia (AIHA). At initial presentation our patient had compensated
      haemolysis and was DAT positive for complement only. Severe haemolytic anaemia
      developed some years later with a negative DAT. Spherocytes were not a feature of
      the blood film and osmotic fragility studies were negative. Immune mediated
      haemolysis was confirmed by fluorescent activated cell sorter (FACS) analysis
      using antihuman IgG immunoglobulin. Response to immunosuppression was transient
      but a good response was achieved following splenectomy. Repeat FACS analysis post
      splenectomy demonstrated a marked rise in IgG coated red cells. Techniques used
      in establishing the diagnosis and possible mechanisms for this presentation are
      discussed.

PMID- 11318805
TI  - Effect of tourniquet pressure and intra-individual variability on plasma
      fibrinogen, platelet P-selectin and monocyte tissue factor.
AB  - Small differences in levels of certain haemostatic components may be clinically
      significant. It is important therefore to eliminate potential sources of
      confounding variability. This study investigated the effect of removing
      tourniquet pressure prior to sample collection on plasma fibrinogen levels,
      platelet P-selectin and monocyte tissue factor expression. Blood was collected
      from the right arm under maintained tourniquet pressure and from the left arm
      following the release of pressure once the vein was sufficiently inflated for
      insertion of a needle. Whole blood was labelled within one hour of venepuncture
      to allow analysis of platelet P-selectin and monocyte tissue factor by flow
      cytometry. Plasma fibrinogen levels were analysed in samples stored at -70
      degrees C, for all individuals at the end of the study using a method based on
      the Clauss technique. Intra-individual variability for each of the components was
      assessed by collecting samples under tourniquet pressure from four individuals on
      the same day on three consecutive weeks. Intra-individual variations were greater
      than assay CVs for all three components. There were no significant differences
      between the two tourniquet methods of collection for fibrinogen, P-selectin or
      tissue factor. In conclusion, there is no reason not to use a tourniquet during
      collection of blood for analysis of plasma fibrinogen, platelet P-selectin or
      monocyte tissue factor.

PMID- 11318806
TI  - Severe epistaxis in brucellosis-induced isolated thrombocytopenia: a report of
      two cases.
AB  - Brucellosis can present initially with its haematological findings including
      anaemia, leukopenia, and thrombocytopenia and may mimic primary haematological
      diseases. We present two patients with complaints of severe epistaxis and
      isolated thrombocytopenia which was initially diagnosed as idiopathic
      thrombocytopenic purpura but which was finally attributed to brucellosis. Their
      platelet count reverted to normal within 2-3 weeks of initiating antibrucellosis
      treatment with recovery from the disease.

PMID- 11318807
TI  - Vertebral infections caused by Haemophilus aphrophilus: case report and review.
AB  - OBJECTIVE: To review in detail clinical presentation, bacteriologic findings,
      associated conditions and treatment of Haemophilus aphrophilus vertebral
      osteomyelitis and to compare them to a case we report herein. METHODS: A Medline
      (National Library of Medicine) search of the literature was performed by using
      the key words H. aphrophilus, spondylodiscitis, discitis, and vertebral
      osteomyelitis. The references of the case reports were examined for additional
      cases, especially those cited in older articles that had not been entered onto
      the bibliographic database. RESULTS: A case report of spondylodiscitis due to H.
      aphrophilus in a 35-year-old patient with a history of dental abscess 7 months
      before admission is presented. The patient responded well to treatment with
      ceftriaxone and ciprofloxacin. To date, only 14 cases of H. aphrophilus vertebral
      osteomyelitis have been reported. They are usually reported in middle-aged
      patients, usually male. Most recent cases have been treated with
      fluoroquinolones. Duration of treatment usually ranges from 1 to 3 months.
      CONCLUSIONS: H. aphrophilus is an uncommon cause of vertebral osteomyelitis.
      Patients are regularly cured by antibiotic therapy, provided that a tissue biopsy
      is performed in order to isolate the causative bacterium.

PMID- 11318808
TI  - Effect of some fractions of alveolar surfactant (phospholipids and SP-A) on the
      bactericidal activity of different antimicrobials against some respiratory
      pathogens.
AB  - OBJECTIVES: To investigate the effects of physiologic concentrations, at alveolar
      level, of some fractions of pulmonary surfactant (phospholipids and SP-A) on the
      bactericidal activity of different antimicrobials against some respiratory
      pathogens. METHODS: The antimicrobial agents cefdinir, sparfloxacin,
      clarithromycin, teicoplanin, cefepime, ciprofloxacin, netilmicin and tobramycin,
      depending on their specific activity, were investigated against Staphylococcus
      aureus, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis,
      Klebsiella pneumoniae and Pseudomonas aeruginosa. Killing curves were carried out
      with antimicrobials at 0.5 and 2 MIC, SP-A at 1 and 5 mg/L and phospholipids at
      50 mg/L. RESULTS: Time-kill experiments showed that while SP-A never modified the
      activity of antimicrobials, phospholipids exerted, in some cases, a weak
      antagonistic effect. Among antibacterials and pathogens investigated,
      phospholipids were able to decrease the rate of killing of cefepime and
      ciprofloxacin only on P. aeruginosa, both at 0.5 and at 2 MIC, with an increase
      of about 1 log in CFU. The combination of SP-A and phospholipids never modified
      the effect observed in the presence of lipids alone. CONCLUSIONS: The paucity of
      data only allow us to observe that the examined antibiotics do not have
      substantially reduced activity against respiratory pathogens studied in the
      presence of physiologic concentrations of some fractions of surfactant. Cefepime
      alone already exerted a small effect, and ciprofloxacin at 2 MIC, even in the
      presence of phospholipids, retained its bactericidal activity.

PMID- 11318809
TI  - Quantitative detection of Toxoplasma gondii DNA in human body fluids by TaqMan
      polymerase chain reaction.
AB  - OBJECTIVE: A new quantitative polymerase chain reaction (real-time PCR) was
      designed to detect Toxoplasma DNA in human body fluid samples. METHODS: Real-time
      fluorescence detection of amplification product formation on the basis of the
      TaqMan-System was established with Toxoplasma 18S rDNA as a target gene. RESULTS:
      The method provides a high sensitivity comparable to conventional nested PCR
      procedures and generates quantitative data when detecting toxoplasmic DNA in
      human blood, cerebrospinal or amniotic fluid. Moreover, data were obtained
      investigating blood samples from an immunocompromised patient with reactivated
      toxoplasmosis after allogeneic bone marrow transplantation, monitoring the
      therapeutic effect. CONCLUSIONS: The potential application of this method to
      detect Toxoplasma DNA in body fluids and to follow the development of parasitemia
      under therapy could be demonstrated.

PMID- 11318810
TI  - The effects of live Streptococcus pneumoniae and tumor necrosis factor-alpha on
      neutrophil oxidative burst and beta 2-integrin expression.
AB  - OBJECTIVE: To study the effects of TNF-alpha and live Streptococcus pneumoniae on
      human neutrophil oxidative burst and beta 2-integrin expression using flow
      cytometry. METHODS: Six clinical isolates of S. pneumoniae (serotypes 3, 19A,
      22F, 6A, 33F and 9N) from patients with bacteremic pneumonia or upper respiratory
      tract infections were studied. Whole blood was incubated either alone, with TNF
      alpha or with S. pneumoniae or with both TNF-alpha and pneumococci at a ratio of
      one neutrophil per 1--5 bacteria. After 30 min of incubation, the tubes were put
      into ice, fixed and analysed. RESULTS: S. pneumoniae caused an increase in
      oxidative burst but not greater than that caused by TNF-alpha alone. When whole
      blood was preincubated with TNF-alpha for 30 min before the addition of
      pneumococci, a further increase in the oxidative burst response was seen. The
      variation in CD11b expression was not significant. Both S. pneumoniae and TNF
      alpha caused increases in CD18 expression. The addition of TNF-alpha directly
      with the bacteria caused no further increase, but preincubation of blood with TNF
      alpha 30 min before the addition of the bacteria caused a significant increase in
      CD18 expression. CONCLUSIONS: Live S. pneumoniae stimulates polymorphonuclear
      leukocytes to produce an oxidative burst and increases expression of CD18, and
      these effects are enhanced by TNF-alpha.

PMID- 11318811
TI  - Isolation and in vitro susceptibility to amphotericin B, itraconazole and
      posaconazole of voriconazole-resistant laboratory isolates of Aspergillus
      fumigatus.
AB  - OBJECTIVES: To select voriconazole-resistant mutants of Aspergillus fumigatus in
      the laboratory from drug-susceptible clinical isolates and examine their in vitro
      susceptibility to amphotericin B and investigational azoles, and to compare the
      intramycelial accumulation of voriconazole in the resistant isolates with that in
      the susceptible parent. METHODS: Voriconazole-resistant Aspergillus fumigatus
      isolates were selected in the laboratory from three highly susceptible (MIC < or
      = 0.5 mg/L) clinical isolates by stepwise selection on peptone yeast extract
      glucose (PYG) agar containing 0.5 mg and 4 mg voriconazole/L. Twenty-three
      colonies that grew in the presence of 4 mg voriconazole/L on PYG agar (frequency
      1.9 x 10(-8)) were tested for their in vitro susceptibility to amphotericin B,
      itraconazole, voriconazole and posaconazole by a broth macrodilution technique.
      The accumulation of voriconazole in the mycelia of two representative resistant
      isolates (VCZ-W42 and VCZ-W45) was determined by a previously described bioassay.
      RESULTS: The geometric mean MICs (mg/L) of amphotericin B, itraconazole,
      voriconazole and posaconazole for these isolates were 0.45 +/- 0.19, 0.69 +/-
      0.45, 5.24 +/- 3.74 and 0.27 +/- 0.18, respectively. A comparison of the
      geometric mean MICs of the antifungals obtained for the resistant isolates to
      those of the susceptible parents showed 1.15-, 2.76-, 16.90- and 1.42-fold
      increases, respectively, for amphotericin B, itraconazole, voriconazole and
      posaconazole, suggesting that low-level cross-resistance exists between the azole
      antifungals. The susceptible parent and the resistant isolates accumulated
      similar amounts of voriconazole. CONCLUSIONS: These results suggest that
      spontaneous mutants of Aspergillus fumigatus resistant to voriconazole could
      emerge among clinical isolates under selection pressure and that the observed
      reduced in vitro susceptibility to voriconazole may not be due to reduced
      accumulation of the drug in the mycelia.

PMID- 11318812
TI  - Prevalence of Yersinia plasmid-encoded outer protein (Yop) class-specific
      antibodies in patients with Hashimoto's thyroiditis.
AB  - OBJECTIVE: To investigate the prevalence of class-specific antibodies (IgG, IgA)
      to Yersinia enterocolitica plasmid-encoded outer proteins (Yops) in patients with
      diagnosed Hashimoto's thyroiditis. METHODS: Seventy-one patients with Hashimoto's
      disease, 464 healthy blood donors and 250 patients with non-postinfectious
      rheumatic disorders (matched controls) were tested for class-specific antibodies
      to Yops. Anti-Yop antibodies were determined by ELISA and Western blot. RESULTS:
      The prevalence of class-specific antibodies to Yops as determined by ELISA was 14
      fold higher (20 of 71; 28.2%) in people with Hashimoto's thyroiditis than in the
      two control groups. These results were confirmed by the Western blot, with 16
      positive sera, three equivocal and one negative. CONCLUSIONS: There is strong
      clinical and seroepidemiologic evidence for an immunopathologic causative
      relationship between Yersinia enterocolitica infection and Hashimoto's
      thyroiditis. Further investigation concerning the mechanisms involved and the
      possible effects of antibacterial chemotherapy on the outcome of Hashimoto's
      disease is warranted.

PMID- 11318813
TI  - Effect of beta-lactam antibiotics on the in vitro development of resistance in
      Pseudomonas aeruginosa.
AB  - OBJECTIVE: To investigate whether stepwise selection of resistance mutations may
      mirror the continued bacterial exposure to antibiotics that occurs in the
      clinical setting. METHODS: We examined the in vitro development of resistance to
      a number of commonly used antibiotics (cefepime, cefpirome, ceftazidime,
      cefotaxime, piperacillin and imipenem) in Pseudomonas aeruginosa, a significant
      nosocomial pathogen. Stepwise resistance was assessed by serial passage of
      colonies located nearest to the inhibition zone on antibiotic-containing gradient
      plates. RESULTS: The lowest frequencies of spontaneous resistance mutations were
      found with cefepime and imipenem; these drugs also resulted in the slowest
      appearance of resistance of spontaneous resistance mutations. In five wild-type
      P. aeruginosa strains, cefepime-selected isolates required a mean of 30 passages
      to reach resistance; resistance occurred more rapidly in strains selected with
      other cephalosporins. P. aeruginosa strains that produced beta-lactamase or non
      enzymatic resistance generally developed resistance more rapidly than wild-type
      strains. For most strains, resistance to all antibiotics except imipenem
      correlated with increased levels of beta-lactamase activity. Cross-resistance of
      cephalosporin-selected resistant mutants to other cephalosporins was common.
      Cephalosporin-resistant strains retained susceptibility to imipenem and
      ciprofloxacin. CONCLUSIONS: From our in vitro study, we can conclude that the
      rate of development of resistance of P. aeruginosa is lower with cefepime
      compared with other cephalosporines.

PMID- 11318814
TI  - Antimicrobial resistance in viridans group streptococci among patients with and
      without the diagnosis of cancer in the USA, Canada and Latin America.
AB  - OBJECTIVE: To investigate antimicrobial resistance in viridans group streptococci
      (VGS) among patients with and without the diagnosis of cancer in the USA, Canada
      and Latin America. METHODS: All bloodstream isolates of VGS collected from SENTRY
      centers in the Western Hemisphere between January 1997 and December 1999 were
      tested by reference broth microdilution methods (NCCLS). Results for isolates
      from patients with cancer were compared to those from other patient populations.
      RESULTS: Overall, 438 unique patient bloodstream isolates of VGS were collected
      during the study. Percentage susceptible/MIC90 (mg/L) values for antimicrobials
      tested were as follows: penicillin, 66/1; erythromycin, 60/4; clindamycin,
      92/0.12; cefepime, 86/1; trimethoprim-sulfamethoxazole, 80/2; ciprofloxacin, 44/>
      2; gatifloxacin, 98/0.5; and vancomycin, 100/1. Of these isolates, 70 (16%) were
      confirmed to be from cancer patients. VGS isolates from cancer patients were less
      susceptible to most antimicrobials tested than were isolates from non-cancer
      patients. The greatest differences in susceptibility rates for cancer- versus non
      cancer-associated VGS isolates were seen for ciprofloxacin (34% versus 46%, P =
      0.07) and trimethoprim-sulfamethoxazole (64% versus 83%, P < 0.001), two agents
      which are often used for prophylaxis or as presumptive therapy in cancer
      patients. CONCLUSIONS: Susceptibility rates for VGS isolates from cancer patients
      are lower than those for isolates from patients without a cancer diagnosis. These
      differences are greatest for agents that have seen widespread prophylactic and
      empirical use. Ongoing surveillance of VGS infections in this patient population
      is important and should help to guide therapy decisions.

PMID- 11318815
TI  - Assessment of five culture media for the growth and isolation of Capnocytophaga
      spp.

PMID- 11318816
TI  - Bactericidal activity of moxifloxacin against Staphylococcus aureus.

PMID- 11318817
TI  - PCR detection of Streptococcus pneumoniae DNA in serum samples for pneumococcal
      pneumonia diagnosis.

PMID- 11318818
TI  - Treatment of tularemia with levofloxacin.

PMID- 11318819
TI  - The antibiotic food-chain gang.

PMID- 11318820
TI  - Day-to-day variation in oxygen consumption at submaximal loads during ergometer
      cycling by adolescents.
AB  - The day-to-day variation in oxygen consumption (VO2) during ergometer cycling by
      20 healthy adolescents, 10 females and 10 males, was measured using indirect
      calorimetry. The two sets of measurements were performed on two consecutive days.
      Great care was taken to minimize possible disturbing factors. Cycling started at
      50 and 100 W for female and male adolescents, respectively. The load was
      increased at a rate of 5 W 30 s(-1). In order to reach steady state, the load was
      kept constant for 3.5 min twice during the cycling session, at 100 and 130 W for
      the females and at 130 and 160 W for the males. Cycling continued until
      exhaustion. The maximal loads were 196 W (mean) and 271 W (mean) for females and
      males, respectively. At the maximal loads the day-to-day variation (+/-2 SD) in
      oxygen consumption (VO2) was +/-330 ml min(-1) for females and 390 ml min(-1) for
      males. At the submaximal loads the day-to-day variation in heart rate (HR) was
      9.3 beats min(-1) (+/-2 SD) (coefficient of variation, CV=3.4% at 130 W) for both
      sexes. The day-to-day variation in oxygen consumption (VO2) was +/-199 ml min(-1)
      (+/-2 SD) at the different submaximal loads and did not differ between female and
      male adolescents (CV=5.7% at 130 W). This natural day-to-day variation must be
      taken into consideration when using a submaximal ergometer cycling test for the
      evaluation of physical capacity in the two sexes.

PMID- 11318821
TI  - Excessive exercise ventilation in moderate left heart dysfunction. Influence of
      postural changes in central haemodynamics and blood gases.
AB  - To evaluate the relative importance of pulmonary congestion and peripheral
      hypoxia as causes for the excessive exercise ventilation in left heart
      dysfunction, seven patients with excessive ventilation and distinct left heart
      dysfunction during moderate exercise (LHD), and seven control patients with
      essentially normal exertional functions (CTR), had ventilation, central
      haemodynamics, arterial and mixed venous blood gases examined at rest and
      exercise, 32 W (25-40) in the LHD group and 44 W (33-49) in the CTR group, in
      lying and sitting positions. Change from lying to sitting exercise, led to fall
      in pulmonary artery wedge pressure (PAWP) from 31.0 +/- 5.5 to 8.8 +/- 5.0 mmHg
      in the LHD group, compared with from 13.7 +/- 1.0 to 2.1 +/- 2.4 mm Hg in the
      controls, while ventilation/O2 intake ratio (V/VO2) and physiological dead
      space/tidal volume ratio (VD/VT) showed a tendency to rise, from 36.3 +/- 8.8 to
      39.2 +/- 7.4, and from 0.35 +/- 0.11 to 0.39 +/- 0.09, respectively, in the LHD
      group, and from 27.5 +/- 3.1 to 28.7 +/- 5.3, and from 0.19 +/- 0.09 to 0.21 +/-
      0.12 in the controls. Mixed venous O2 tension (PvO2) showed a marked decline from
      3.60 +/- 0.33 to 3.26 +/- 0.36 kPa in the LHD group, as compared with from 3.94
      +/- 0.28 to 3.71 +/- 0.29 kPa in the controls, while the calculated physiologic
      shunt (Qs/Qt) suggested improved alveolo-arterial gas exchange. The data fit in
      with recent studies ascribing the excessive exercise ventilation to a combination
      of signals from hypoxia-induced changes, particularly in the exercising muscles,
      and augmented ergoreflex and central and peripheral chemoreceptor activity,
      partly to changes in the integrated control of ventilation and circulation, not
      to mechanisms related to pulmonary congestion.

PMID- 11318822
TI  - Capnography in spontaneously breathing preterm and term infants.
AB  - OBJECTIVE: To investigate sidestream EtCO2 wave patterns as related to
      prematurity. DESIGN: The EtCO2 wave pattern was analyzed longitudinally in 20
      sequential preterm, 32-37 weeks of gestation and 39 fullterm controls. Infants
      with a cardiorespiratory disease, neurological deficit or a metabolic disorder
      were not included in the study. Sidestream EtCO2 was employed. Wave patterns were
      identified and baseline expiratory/inspiratory length and wave amplitude were
      measured. RESULTS: Two predominant (about 75%) wave patterns were identified: (i)
      (with plateau) significantly more prevalent among infants born at term as
      compared with preterm infants across their postconceptional ages (PCA) (P=0.005
      0.04), (ii) (plateau free) significantly more prevalent among the youngest
      preterm infants as compared with the fullterm controls. Expiratory length was
      significantly correlated with respiratory rate (RR) across ages (P=0.01-0.001)
      whereas inspiratory length was correlated with RR among the two youngest groups
      of infants only (P=0.002 and 0.004). Wave patterns were not found to be affected
      by environmental temperatures, blood pressure, body weight, haemoglobin level,
      aminophylline or O2 supplementation. CONCLUSION: These findings suggest that
      EtCO2 wave pattern distribution among preterm infants is distinctly different
      from that of term controls, regardless of PCA, while inspiration is related to
      the degree of maturity. Alveolar pathology could probably be missed by sidestream
      capnography.

PMID- 11318823
TI  - Is oscillometric ankle pressure reliable in leg vascular disease?
AB  - The objective of the study was to evaluate the validity of oscillometric systolic
      ankle pressure in symptomatic leg arterial occlusive disease. Ankle pressure
      measurements using oscillometric curves obtained using a standard 12-cm cuff with
      a specially designed device for signal processing were validated against the
      continuous wave (CW) Doppler technique. Thirty-four subjects without signs or
      symptoms of peripheral vascular disease (68 legs) and 47 patients with leg
      ischaemia (85 legs) varying from moderate claudication to critical ischaemia were
      examined. The oscillometric curves were analysed using several algorithms
      reported in the literature, based on the assumption that maximum oscillations are
      recorded near mean arterial pressure. In normals, reasonable agreement between CW
      Doppler and oscillometric methods was seen. When an algorithm that determined the
      lowest cuff pressure at which maximum oscillations occurred, and a characteristic
      ratio for systolic pressure of 0.52 was used, the mean difference between CW
      Doppler and oscillometry was 1.7 mmHg [range -19 to +27, limits of agreement (2
      SD) 21.1 mmHg]. In ischaemic legs, oscillometry overestimated systolic ankle
      pressure by a mean of 28.8 mmHg [range -126 to +65, limits of agreement 82.8
      mmHg]. The difference was more pronounced among patients with critical ischaemia
      compared with claudicants, and also more evident among diabetics. The error of
      oscillometric pressure determination in subjects with leg arterial disease
      inversely increased with CW Doppler ankle pressure. In 39% of the recordings in
      legs with a CW Doppler systolic pressure below 100 mmHg, the oscillometric mean
      arterial pressure was higher than the recorded CW Doppler systolic pressure. In
      conclusion, the oscillometric method to determine systolic ankle pressure, based
      on the concept of maximum cuff oscillations occurring near mean arterial
      pressure, is not reliable in leg arterial disease, usually overestimating ankle
      pressure.

PMID- 11318824
TI  - Renal extraction of insulin and C-peptide in man before and after a glucose meal.
AB  - It was recently shown that the early rise in arterial insulin concentration after
      an oral glucose meal is largely because of a decreased extraction of the hormone.
      The kidney is a major site for extraction of insulin and C-peptide. We therefore
      measured the renal extraction of insulin and C-peptide in eight healthy
      individuals before and after ingestion of 75 g of glucose. Arterial, renal venous
      and hepatic venous catheters were inserted. Splanchnic and renal plasma flow were
      measured, as well as arterial, hepatic venous and renal venous concentrations of
      insulin and C-peptide. Renal fractional extraction of insulin increased
      significantly, from 21% to a maximum of 48% after the meal while the renal
      fractional extraction of C-peptide did not change significantly. Renal blood flow
      decreased slightly but significantly after the meal. It is concluded that renal
      fractional extraction of insulin increases and that renal blood flow decreases
      after a glucose meal.

PMID- 11318825
TI  - Endocrine responses to 7 days of head-down bed rest and orthostatic tests in men
      and women.
AB  - The objective of this study was to investigate plasma volume (PV), total body
      water, hormones and hydroelectrolyte responses in eight males (25-40 years) and
      eight females (25-31 years) during 7 days of exposure to simulated microgravity (
      6 degrees head-down bed rest, HDBR). Bed rest is a model that has commonly been
      used to simulate spaceflight. Heart rate (HR), blood pressure (BP) and vasoactive
      hormone responses were studied before and after HDBR during a 10-min stand test.
      No change in total body water and body mass was noted in either sex. The decrease
      in PV was similar in both men (9.1 +/- 1.4%) and women (9.4 +/- 0.8%). Urinary
      normetanephrine (NMN) was decreased during HDBR in both sexes. Urinary
      metanephrine (MN) and plasma catecholamines were unchanged. Daily urinary
      excretion of urea, an indirect index of protein breakdown, was increased only in
      the female subjects during HDBR. Plasma active renin (AR) and aldosterone were
      increased in both sexes, but urinary atrial natriuretic peptide (ANP) and
      arginine vasopressin (AVP) were unchanged throughout the study. Also, the
      hormonal responses to 7 days of HDBR were comparable between men and women.
      Moreover, the results show similar cardiovascular and endocrine responses to
      standing after HDBR. However, the orthostatic intolerance following HDBR was
      associated with a blunted increase in noradrenaline (NA) only in the women during
      the stand test. It is concluded that: (i) 7 days of physical inactivity achieved
      during HDBR resulted in a reduced sympathetic activity in both sexes and
      alterations in protein metabolism in women and (ii) standing after HDBR resulted
      in an attenuated release of noradrenaline in women.

PMID- 11318826
TI  - Circadian rhythm of core body temperature in subjects with chronic fatigue
      syndrome.
AB  - The pathophysiological basis for chronic fatigue syndrome (CFS) remains poorly
      understood. Certain symptoms of CFS, namely fatigue, neurocognitive symptoms and
      sleep disturbance, are similar to those of acute jet lag and shift work syndromes
      thus raising the possibility that CFS might be a condition associated with
      disturbances in endogenous circadian rhythms. In this study, we tested this
      hypothesis by examining the circadian rhythm of core body temperature (CBT) in
      CFS and control subjects. Continuous recordings of CBT were obtained every 5 min
      over 48 h in a group of 10 subjects who met the Center for Disease Control (CDC)
      definition of CFS and 10 normal control subjects. Subjects in the two groups were
      age, sex and weight-matched and were known to have normal basal metabolic rates
      and thyroid function. CBT recordings were performed under ambulatory conditions
      in a clinical research centre with the use of an ingestible radio frequency
      transmitter pill and a belt-worn receiver-logger. CBT time series were analysed
      by a cosinor analysis and by a harmonic-regression-plus-correlated-noise model to
      estimate the mean, amplitude and phase angle of the rhythm. The goodness of fit
      of each model was also compared using the Akaike Information Criterion (AIC) and
      sigma2. Average parameters for each group were compared by Student's t-test. By
      cosinor analysis, the only significant difference between CFS and control groups
      was in the phase angle of the third harmonic (P=0.02). The optimal harmonic
      regression-plus-correlated-noise models selected were ARMA(1,1): control 7, CFS
      6; ARMA(2,0): control 1, CFS 4; and ARMA(2,1): control 2 subjects. The optimal
      fit ARMA model contained two harmonics in eight of 10 control subjects but was
      more variable in the CFS subjects (1 harmonic: 5 subjects; 2 harmonics: 1
      subject; 3 harmonics: 4 subjects). The goodness of fit measures for the optimal
      ARMA model were also better in the control than the CFS group, but the
      differences were not statistically significant. We conclude that, measured under
      ambulatory conditions, the circadian rhythm of CBT in CFS is nearly
      indistinguishable from that of normal control subjects although there was a
      tendency for greater variability in the rhythm. Hence, it is unlikely that the
      symptoms of CFS are because of disturbance in the circadian rhythm of CBT.

PMID- 11318827
TI  - Evaluation of various electrocardiographic criteria for left ventricular
      hypertrophy in patients with stable angina pectoris: influence of using modified
      limb electrodes.
AB  - BACKGROUND: Left ventricular hypertrophy (LVH) in coronary heart disease is
      associated with poor prognosis. Electrocardiography (ECG) criteria for LVH, when
      using ECG with modified limb electrode positions, has not been validated in
      patients with angina pectoris. METHODS: Echocardiography and resting ECGs with
      modified limb electrode positions, i.e. with the limb leads placed on the abdomen
      instead of the extremities, were registered from 468 patients (295 men) with
      stable angina pectoris. To evaluate the influence of using modified limb
      electrode positions, ECGs with standard and modified limb electrode positions
      were compared in a control group consisting of 50 other patients. RESULTS: The
      ECG criteria for LVH according to the Perugia score, the Minnesota code and
      Romhilt & Estes reached the highest sensitivity values, 27-31% in men and 24-38%
      in women, while the sensitivities of different Cornell criteria were as low as 6
      10% in men and 19-29% in women. In the control group, the R- and S-wave
      amplitudes of the precordial leads were only slightly changed, as expected,
      whereas those of the limb leads changed considerably. Based on these results, we
      corrected aVL in the main study, which increased the sensitivity of the Cornell
      voltage criteria from 15 to 30%, while the specificity was maintained at 95%.
      CONCLUSIONS: ECGs registered with modified limb electrode positions can be used
      to detect LVH with traditional ECG criteria, but changes in the limb leads are
      considerable and influence the sensitivities.

PMID- 11318828
TI  - Changes of heart rate and blood pressure in registration of forced respiration
      flow-volume loop.
AB  - Changes in heart rate (HR) and finger mean blood pressure (MBP) during
      registration of the flow-volume loop of forced respiration in healthy young
      subjects were studied. Breathing patterns of performing the flow-volume loop of
      forced respiration (forced respiratory manoeuvre, FRM) as well as the related
      responses of cardiovascular parameters in different subjects were found to vary
      to a large extent. FRM has a remarkable influence on the cardiovascular system:
      during FRM the peak values of MBP were 19 +/- 9 mmHg higher than baseline values
      and the peak values of HR were 30 +/- 11 beats min-1 higher. We conclude that it
      is essential to pay attention to a remarkable elevation of blood pressure in
      functional breathing tests in patients with high blood pressure.

PMID- 11318829
TI  - A practical method to statistically classify devices according to their relative
      accuracy.
AB  - Mathematical methods to statistically compare the relative accuracy of
      physiological monitoring devices to reference measurements are scarce. We
      developed such a method to compare any number of devices to each other as well as
      to reference values. This new statistical comparative procedure uses a
      combination of different known mathematical processes. The method allows the
      separation of the error of the devices into two components, the first, being
      systematic, can be easily amended, while the second, inherent to the technical
      limitations of the measuring device as well as to the physical properties of the
      explored phenomenon, cannot be corrected and will thus be used as the comparative
      criterion for statistics. That method, which is easy to implement should ease
      comparisons of the accuracy of any number of devices as well as comparison of
      other sets of physiological values, by giving an easy access to statistical
      results.

PMID- 11318830
TI  - Tracheal sounds and airflow dynamics in surgically treated unilateral vocal fold
      paralysis.
AB  - The aim of this study was to investigate the changes in tracheal sounds and
      airflow dynamics in patients who underwent surgical medialization of a
      unilaterally paralysed vocal fold. Ten adults with unilateral vocal fold
      paralysis but no history of pulmonary diseases were included. Vocal fold
      medialization was performed by an injection of autologous fascia into the
      paralysed vocal fold. Recording of tracheal sounds, flow-volume spirometry and
      body plethysmography were carried out before and 4-14 months after the operation.
      The mean number of inspiratory wheezes per respiratory cycle increased from 0.02
      (range 0-0.10) to 0.42 (range 0-0.86) and the mean number of expiratory wheezes
      per respiratory cycle from 0.03 (range 0-0.20) to 0.36 (range 0-0.89). The
      increment was statistically significant (P=0.03 and P=0.04, respectively). The
      mean expiratory sound amplitude, in terms of root mean square (RMS), increased
      from 31.5 dB (range 24.0-38.0) to 34.9 dB (range 25-42) (P=0.03) and the average
      peak inspiratory flow (PIF) decreased from 4.63 l s-1 (range 2.84-7.51) to 4.03 l
      s-1 (range 2.27-6.68) (P=0.01). The results indicate that when the paralysed
      vocal fold is brought into midline by a surgical procedure, the prevalence of
      inspiratory and expiratory wheezes increases and sound intensity rises. According
      to this preliminary data tracheal sound analysis gives additional information for
      the assessment of the subtle changes in the larynx.

PMID- 11318831
TI  - Evaluation of impaired dynamic cerebral autoregulation by the Mueller manoeuvre.
AB  - Arterial blood pressure (ABP) shows polyphasic changes during the Mueller
      manoeuvre (voluntary negative intrathoracic pressure). The aim of the present
      study was to investigate (1) whether these changes could be applied to detect
      impaired dynamic cerebral autoregulation (dCA) in carotid stenosis and (2)
      whether the degree of indicated impairment correlates with transfer function
      phase as another current measure for dCA (deep breathing method) and CO2
      reactivity. We examined 13 patients with severe unilateral carotid artery
      stenosis and 16 age-matched controls during 15-s Mueller manoeuvres (MM) at -30
      mmHg using bilateral transcranial Doppler sonography and non-invasive ABP
      recordings (Finapres, 2300, Ohmeda, Englewood, CO, USA). After an initial
      biphasic oscillation, cerebral blood flow velocity (CBFV) and ABP decreased to
      below baseline. CBFV reincreased in controls and on contralateral sides in
      patients 6.0 s (3.8-9.5 s, median and range) after the onset of the decrease,
      despite a further fall in ABP. CBFV over the affected side revealed a
      significantly delayed reincrease (8.0 (5.6-10.3) s; P<0.01) combined with a
      relatively flat and inertial amplitude behaviour. An applied autoregulation index
      derived from the MM (mROR), phase shift and CO2-reactivity were severely reduced
      on the affected side in patients (P<0.01). Reduction of the mROR correlated
      significantly with reduction of phase shift (r=0.69; P=0.002) and CO2-reactivity
      (r=0.78; P=0.002). In conclusion, the different cerebral haemodynamic pattern
      during the MM in patients is likely to reflect impaired dCA. The degree of
      indicated impairment correlates with that of transfer function phase and CO2
      reactivity. Therefore, the MM represents a convenient method for grading of
      compromised cerebral haemodynamics in patients with carotid artery stenosis.

PMID- 11318832
TI  - Changes in cardiac autonomic regulation after prolonged maximal exercise.
AB  - Harmful cardiac events occurs frequently after exercise. However, the cardiac
      autonomic regulation after vigorous exercise is not well known. This study was
      designed to assess heart rate (HR) variability before and after a 75 km cross
      country skiing race. HR variability was assessed by using standard statistical
      measures along with spectral and quantitative Poincare plot analysis of HR
      variability in 10 healthy male subjects (age 36 +/- 11 years). The average HR was
      at the same level 1 day after the race as before the race, but on the second day,
      HR was significantly lower (P<0.001) compared with the prerace and 1 day after
      values. The normalized high-frequency (HF) spectral component of HR variability
      (nuHF) was lower (P<0.01) on the first day after the maximal exercise compared
      with the pre-exercise values but returned to or even exceeded the prerace level
      on the second day (P<0.01). The changes in short-term R-R interval variability
      analysed from the Poincare plot were similar to those observed in the HF spectral
      component. The normalized low-frequency (LF) spectral component of HR variability
      (nuLF) was higher (P<0.01) on the first day after the exercise compared with the
      prerace levels and it also returned to the pre-exercise level or even dropped
      below it on the second day after the race. The mean time it took the HF spectral
      component to return to the pre-exercise level was 4.2 +/- 4.2 h (ranging from 0
      to 12 h). This recovery time correlated inversely with the maximal oxygen
      consumption (VO2max) measured during the bicycle exercise test before the skiing
      race (r=-0.712, P<0.016). The cardiac vagal outflow is blunted for several hours
      after prolonged vigorous exercise. The recovery time of reduced vagal outflow
      depends on individual cardiorespiratory fitness and there is an accentuated
      rebound of altered autonomic regulation on the second day after prolonged
      exercise.

PMID- 11318833
TI  - Factors influencing 133-xenon washout in a nose-sinus model.
AB  - The 133-xenon washout technique is a non-invasive method for the evaluation of
      ventilation of the paranasal sinuses. The half-time of 133-xenon washout (T(1/2))
      is considered to reflect sinus ostial function and sinus ventilation. However, it
      is not known how morphological and physiological factors affect the washout from
      the paranasal sinuses. The aim of the present study was to evaluate how sinus
      volume, ostial diameter and nasal ventilation influence 133-xenon washout in a
      nose-sinus model. This is important for the interpretation of measurements of 133
      xenon washout from paranasal sinuses in healthy subjects and in subjects with
      sinus disease. The 133-xenon washout was measured with a scintillation camera.
      The statistical analysis of the results showed that the logarithm (to the base
      10) of the half-time of 133-xenon washout is linearly related to the ostial
      diameter, the sinus volume and the nasal ventilation in the model. In a multiple
      linear regression model, the most important factor contributing to 133-xenon
      washout was found to be the ostial diameter, which explained 76% of the variation
      in log T(1/2). In the same statistical model the sinus volume explained 7.5% and
      the ventilation 5.3% of the variation in log T(1/2). Calculations of the
      functional ostial diameter in healthy subjects were made, based on the results of
      the model study. The mean functional ostial diameter was found to be 3.5 mm
      (range 0.5-7.5 mm). The results obtained with the present model experiments may
      be of importance for the correct interpretation of the results of measurements of
      133-xenon washout in healthy subjects and patients.

PMID- 11318834
TI  - Gastrointestinal mean transit times in young and middle-aged healthy subjects.
AB  - To investigate the effects of age and gender on gastric, small intestinal and
      colonic mean transit times, a study was conducted in 32 healthy volunteers: eight
      young women (22-30 years), eight young men (20-28 years), eight middle-aged women
      (43-51 years) and eight middle-aged men (38-53 years). After ingestion of a meal
      containing 111Indium-labelled water and 99mTechnetium-labelled omelette imaging
      of the abdomen was performed at intervals of 30 min until all radioactivity was
      located in the colon and henceforth at intervals of 24 h until all radioactivity
      had cleared from the colon. Gastric, small intestinal and colonic mean transit
      times were calculated. The gastric, small intestinal and colonic mean transit
      times were significantly longer in women. Ageing was shown to accelerate the
      gastric and small intestinal transit significantly. In the group of men the
      colonic mean transit time was unaffected by age, but middle-aged women had a
      significantly slower colonic transit than young women. We therefore conclude that
      both age and gender have to be considered when reference values for gastric,
      small intestinal and colonic mean transit times have to be established.

PMID- 11318835
TI  - Asthma, asthma medication and autonomic nervous system dysfunction.
AB  - Asthma is associated with autonomic nervous imbalance: an increased bronchial
      sensitivity to cholinergic constrictors and possibly a decreased sensitivity to
      beta2-adrenergic dilators have been reported in this disease. Also, non
      adrenergic and non-cholinergic (NANC) mediators have a small regulatory effect on
      airway function. These mediators contribute to the pathogenesis of asthma not
      only by regulating smooth muscle tone in the airways but also by affecting
      pulmonary blood flow, endothelial permeability and airway secretions. In many
      studies increased parasympathetic responsiveness has been associated with
      clinical asthma or the worsening of asthma in adults. However, most of the
      studies in children have not found association between autonomic dysfunction and
      asthma. Therefore, the autonomic dysfunction in asthma may be related to more
      advanced disease or long-term asthma medication in adults. This article briefly
      reviews the relationships between airway inflammation, beta2-agonist,
      anticholinergic and glucocorticoid medication as well as autonomic nervous
      function in asthma.

PMID- 11318836
TI  - Coeliac disease and Type 1 diabetes mellitus - the case for screening.
AB  - AIM: To review the relationship between coeliac disease and Type 1 diabetes
      mellitus with emphasis on prevalence of coeliac disease, presentation and
      implications for screening. METHODS: Papers collected over many years by the
      author have been included in the review and a literature search employing Medline
      was undertaken to August 2000. Search words used were coeliac disease and
      diabetes mellitus. RESULTS: Twenty papers exploring the prevalence of coeliac
      disease by serological screening of Type 1 diabetes in children, eight in adults
      and two including both groups were found. An additional 48 papers are included
      and relate to serological screening tests for coeliac disease, expressions and
      complications of coeliac disease, the value of GFD and the genetics of the two
      conditions. Unless formal screening studies are undertaken coeliac disease will
      not be diagnosed because patients are asymptomatic, have atypical symptoms or
      even in those with symptoms the diagnosis is overlooked. Based on small bowel
      biopsy, diagnosis the prevalence of coeliac disease in Type 1 diabetes in
      children is 1:6 to 1:103 and in adults 1:16 to 1:76. Patients may improve
      following the start of a gluten-free diet (GFD) in terms of symptoms, growth in
      children, serum antibody levels, haematological and biochemical indices,
      morphology of the small intestinal mucosa and control of diabetes. CONCLUSION:
      Coeliac disease commonly occurs in Type 1 diabetes. It is recommended that
      screening for coeliac disease should be part of the routine investigation and
      offered to all patients because of the high prevalence and the potential benefits
      of treatment with a GFD. This includes control of symptoms, stabilization of
      diabetes and prevention of complications associated with coeliac disease. The
      cost per patient diagnosed with coeliac disease from the existing population with
      Type 1 diabetes would be pound860 and for those newly arising pound950.

PMID- 11318837
TI  - Relationship between the severity of retinopathy and progression to
      photocoagulation in patients with Type 2 diabetes mellitus in the UKPDS (UKPDS
      52).
AB  - AIM: to establish the degree to which the severity of retinopathy determines the
      risk for the need for subsequent photocoagulation in those with newly diagnosed
      Type 2 diabetes mellitus. METHODS: Of 5102 patients entered into the UK
      Prospective Diabetes Study (UKPDS), 3709 had good quality retinal photographs
      that could be graded at entry. They were followed until the end of the study or
      until lost to follow-up, or until they received photocoagulation. Retinopathy
      severity was categorized as no retinopathy, microaneurysms (MA) only in one eye,
      MA in both eyes or more severe retinopathy features. The risk of photocoagulation
      was assessed in relation to severity of retinopathy at baseline, 3 and 6 years.
      RESULTS: Of the 3709 patients assessed at entry to the UKPDS, 2316 had no
      retinopathy. Of these 0.2% needed photocoagulation at 3 years, 1.1% at 6 years
      and 2.6% at 9 years. Those with MA in one eye only (n = 708) were similar, with
      0%, 1.9% and 4.7% needing photocoagulation by 3, 6 and 9 years, respectively.
      Amongst those who had more retinopathy features at entry (n = 509), 15.3%
      required photocoagulation by 3 years, and 31.9% by 9 years. When those without
      retinopathy at 6 years (n = 1579) were examined 3 and 6 years later (9 and 12
      years after diagnosis), 0.1% and 1.8% required photocoagulation. Those with more
      severe retinopathy (n = 775) needed earlier treatment, 6.6% after 3 years and
      13.3% after 9 years. The commonest indication for laser therapy was maculopathy,
      but those with more severe retinopathy were more likely to be treated for
      proliferative retinopathy and to need both eyes treated. CONCLUSION: Few type 2
      diabetic patients without retinopathy progress to photocoagulation in the
      following 3-6 years, while patients with more severe retinopathy lesions need to
      be monitored closely.

PMID- 11318838
TI  - Relation between homocysteinaemia and diabetic neuropathy in patients with Type 2
      diabetes mellitus.
AB  - AIMS: Limited data are available on determinants of diabetic neuropathy as its
      pathogenesis is multifactorial. Since homocysteine exhibits toxic effects on
      vascular endothelial cells, the association between homocysteine and the
      prevalence of neuropathy in Type 2 diabetes mellitus was investigated. METHODS: A
      total of 65 Type 2 diabetic patients were consecutively enrolled into the study.
      Neuropathy was diagnosed according to clinical symptoms, clinical examination,
      electrophysiological sensory testing and autonomic function testing. With regard
      to homocysteine-related parameters, plasma homocysteine, folate, vitamin B12,
      vitamin B6 and renal function (creatinine, ceratinine clearance, cystatin C) were
      measured, and the C677T polymorphism of the methylenetetrahydrofolate reductase
      gene was determined. RESULTS: Forty-three of the Type 2 diabetic patients were
      classified as suffering from neuropathy. Both patient groups were comparable with
      regard to demographic data, blood pressure, glucose metabolism, renal function
      and homocysteine-related vitamins. In contrast, homocysteine levels (P = 0.04)
      and the frequency of hyperhomocysteinemia (>or= 15 micromol/l) (P = 0.01) were
      significantly increased in neuropathic patients. In a logistic regression model
      with neuropathy as dependent variable, homocysteine (adjusted for creatinine,
      homocysteine-related vitamins, HbA1c and duration of diabetes) was the only
      significant variable associated with the prevalence of neuropathy (odds ratio for
      homocysteine per 5 micromol/l increase: 2.60 (95% confidence interval 1.07
      6.33)). CONCLUSION: The data indicate that homocysteine is independently
      associated with the prevalence of diabetic neuropathy in a collective of Type 2
      diabetic patients. A larger, prospective study would be desirable to clarify the
      role of homocysteine in the pathogenesis of diabetic neuropathy.

PMID- 11318839
TI  - Polynesians: prone to obesity and Type 2 diabetes mellitus but not
      hyperinsulinaemia.
AB  - AIMS: To compare the extent of hyperinsulinaemia among New Zealand Europeans and
      Polynesians (an ethnic group at high risk of Type 2 diabetes mellitus). METHODS:
      A cross-sectional survey from randomly selected households was conducted in inner
      urban South Auckland. Subjects were either European, Maori or Pacific Islands
      Polynesians aged 40-79 years and were screened for diabetes using a random blood
      glucose. Those with an elevated result, and 20% randomly selected from those with
      a normal screening result, were invited to a 75-g glucose tolerance test. WHO
      criteria (1998) for diabetes were used. RESULTS: In those aged 40-59 years, total
      prevalence of diabetes was 7.5 (6.2-9.0)% in Europeans but 21.1 (16.6-25.6)%
      among Maori and 25.0 (19.8-30.1)% among Pacific peoples; obesity (body mass index
      >or= 31.0 kg/m2) was present in 26% Europeans, 63% Maori and 69% Pacific peoples.
      Non-diabetic Polynesians were relatively hyperglycaemic and hyperinsulinaemic.
      After adjusting for the degree of obesity, Polynesians had similar insulin levels
      to Europeans. CONCLUSIONS: These findings indicate that Polynesians are not
      intrinsically insulin resistant as a group, a prerequisite found in most other
      ethnic groups at high risk of Type 2 diabetes mellitus. The high prevalence of
      Type 2 diabetes in Polynesians could be the result of their high prevalence of
      obesity.

PMID- 11318840
TI  - Prolonged QTc interval predicts mortality in patients with Type 1 diabetes
      mellitus.
AB  - AIMS: To evaluate prolonged QTc interval and QT dispersion as predictors of all
      cause and cardiovascular mortality after adjustment for well-established risk
      factors in Type 1 diabetic patients. METHODS: From a cohort of all adult Type 1
      diabetic patients, duration of diabetes >or= 5 years, attending the clinic in
      1984 and followed in an observational study for 10 years (n = 939), all subjects
      with resting baseline electrocardiograms were identified (n = 697, 360 males).
      The QT length was measured and corrected for heart rate (QTc). Maximal QTc length
      (QTc max) and QT dispersion were determined. RESULTS: At baseline, 431 had
      normoalbuminuria (< 30 mg/24 h), 138 had microalbuminuria (30-299 mg/24 h) and
      128 had macroalbuminuria (>or= 300 mg/24 h) of whom 66 (15%), 35 (25%) and 61
      (48%) died during follow-up, respectively (26 (6%), 14 (10%), 21 (16%) from
      cardiovascular disease). QTc max. was 442 (1.2) ms (mean (SEM)) for survivors and
      457 (3.7) in patients who died (P < 0.001). In a Cox proportional hazards model
      including baseline values of putative risk factors, independent predictors of
      death were QTc max (P = 0.03), age (P < 0.001), presence of hypertension (P =
      0.001), male sex (P < 0.001), log urinary albumin excretion (P < 0.001), smoking
      (P = 0.04), log serum-creatinine (P < 0.001), height (P < 0.001), low social
      class (P = 0.04), whereas QT dispersion, heart rate, and HbA1c were not included.
      In the subgroup with macroalbuminuria, but not for all patients, QTc max was an
      independent risk factor for cardiovascular mortality. CONCLUSION: QTc
      prolongation, but not increased QT dispersion, is an independent marker of
      increased mortality in patients with Type 1 diabetes mellitus.

PMID- 11318841
TI  - Association studies of variants in promoter and coding regions of beta-cell ATP
      sensitive K-channel genes SUR1 and Kir6.2 with Type 2 diabetes mellitus (UKPDS
      53).
AB  - AIMS: The beta-cell ATP-sensitive potassium channel consists of two subunits,
      SUR1 and Kir6.2. Population association studies have shown that three variants in
      SUR1 and one in Kir6.2 are associated with Type 2 diabetes. These polymorphisms
      do not result in a functional change or affect splicing, suggesting that they
      could be in linkage disequilibrium with a pathogenic mutation. The present study
      aimed firstly to screen the promoter regions of SUR1 and Kir6.2 to determine
      whether mutations in linkage disequilibrium with the silent variants lie in
      regulatory regions, which might lead to changes in gene expression. Secondly,
      novel and previously described variants associated with Type 2 diabetes (SUR1
      exon 16-3t, exon 18 T, and Kir6.2 E23K) were investigated in the UKPDS cohort.
      METHODS: The promoter sequences of both genes were screened by single-stranded
      conformational polymorphism analysis for variants associated with Type 2
      diabetes. The previously reported variants were evaluated in 364 Type 2 diabetic
      and 328 normoglycaemic control subjects. RESULTS: Two variants were detected in
      the SUR1 promoter, a three base insertion (caa) at -522 bp and a single base
      substitution at - 679 bp (c-->g). Neither of the variants were associated with
      diabetes, nor were they in a sequence consensus region for transcription factors.
      No association with diabetes was observed for either SUR1 variant. However, in
      contrast, analysis of the Kir6.2 E23K variant showed that the KK homozygosity was
      more frequent in Type 2 diabetic than control subjects. Variants were not
      associated with clinical characteristics nor did they affect response to
      sulphonylurea therapy CONCLUSION: There is no support at present for mutations in
      either Kir6.2 or SUR1 promoter sequences contributing to Type 2 diabetes.
      However, the minimal promoter region of SUR1 has yet to be investigated. The E23K
      variant of Kir6.2 is associated with Type 2 diabetes mellitus in the UKPDS
      cohort.

PMID- 11318842
TI  - Factor analysis of thermal and vibration thresholds in young patients with Type 1
      diabetes mellitus.
AB  - AIMS: To identify factors that represent relationships among sets of interrelated
      thermal and vibration threshold variables and to find clinical correlates that
      are significantly associated with these factors. METHODS: Thermal and vibration
      perception thresholds were tested in the hands and feet of Type 1 diabetic
      patients treated in an outpatient clinic for juvenile-onset diabetes. Factor
      analysis was used to identify factors that represent relationships among sets of
      thermal and vibration threshold variables. RESULTS: One hundred and forty-eight
      patients (47.3% males, median current age 22.3 years and median duration of
      diabetes 11.4 years) were evaluated. Three factors explained 77% of the total
      variance: 'hand sensation' factor, underlying cold, warmth and vibration
      perception thresholds in the hand; 'foot sensation' factor, underlying the same
      sensory thresholds in the foot; and 'heat-related pain' factor, underlying heat
      pain perception threshold in both limbs. The 'foot sensation' factor was the only
      factor that significantly correlated with diabetes-related variables (e.g.
      duration and cumulative glycaemic control of the disease) and concurrent diabetic
      microangiopathy. Male sex was associated with higher values of the 'heat-related'
      factor, while the 'hand sensation' factor did not correlate with any of the study
      variables. CONCLUSIONS: The distribution of the various thermal and vibration
      threshold variables according to the three factors may point at length-dependent
      mechanism of axonal degeneration. Cold, warmth and vibration perception
      thresholds in the foot may be the only valuable psychophysical parameters in the
      evaluation of early sensory impairment associated with diabetes.

PMID- 11318843
TI  - Gestational diabetes mellitus in the last trimester - a feature of maternal iron
      excess?
AB  - AIM: To determine whether non-anaemic women with gestational diabetes mellitus
      (GDM) diagnosed in third trimester pregnancy have evidence of increased iron
      stores compared with matched non-diabetic controls. METHODS: In a prospective
      study, women who had antenatal booking before 20 weeks' gestation and without
      anaemia or diabetes mellitus were recruited at the time of the oral glucose
      tolerance test (OGTT) at 28-31 weeks' gestation for the study of serum ferritin,
      iron and transferrin concentrations. The results were blinded to the managing
      obstetricians. After delivery, the records were reviewed. The cases diagnosed as
      GDM were compared with a control group (two controls for each index case matched
      for parity) selected at random from the at-risk but nondiabetic cases. RESULTS:
      GDM was diagnosed in 97 of the 401 women recruited. Compared with the 194
      controls, there was no difference in the weight, body mass index, booking and
      third trimester haemoglobin, or third trimester red cell indices, but
      concentrations of serum ferritin, iron, transferrin saturation, and the post
      natal haemoglobin were significantly higher. On multiple regression analysis,
      maternal BMI and the log-transformed ferritin concentration remained significant
      determinants of the OGTT 2-h glucose value. CONCLUSION: The results suggest an
      association between increased iron stores and glucose intolerance at the third
      trimester in non-anaemic women. The role of iron excess in the pathogenesis of
      GDM needs to be examined.

PMID- 11318844
TI  - Correction of hyperglycaemia reduces insulin resistance and serum soluble E
      selectin levels in patients with Type 2 diabetes mellitus.
AB  - AIMS: To investigate the effects of glycaemic control on insulin sensitivity and
      serum concentrations of soluble vascular cell adhesion molecule (sVCAM)-1 and E
      selectin (sE-selectin) in patients with Type 2 diabetes mellitus. To examine
      whether reductions in serum adhesion molecule levels correlate with improvement
      in insulin resistance. METHODS: A total of 54 patients with Type 2 diabetes were
      treated for 4 weeks with either diet alone, sulphonylurea or insulin. Fasting
      glucose, insulin sensitivity, lipids, sVCAM-1, and sE-selectin levels were
      measured before and after treatment. RESULTS: All treatment modalities
      successfully corrected hyperglycemia. Reductions in blood glucose levels resulted
      in improvement in insulin sensitivity (diet KITT 2.40 +/- 0.26-3.09 +/- 0.36, P <
      0.01; sulphonylurea 2.24 +/- 0.16-2.94 +/- 0.18, P < 0.01; insulin 1.68 +/- 0.27
      2.16 +/- 0.22%/min, P < 0.05), and decrease in sE-selectin levels (diet 88.4 +/-
      14.9-66.2 +/- 10.8, P < 0.05; sulphonylurea 85.1 +/- 11.6-59.8 +/- 7.8, P < 0.01;
      insulin 84.4 +/- 8.7-66.8 +/- 7.4 ng/ml, P < 0.01), but no change in sVCAM-1
      levels. There was a significant correlation between the degree of decrease in sE
      selectin levels and improvement in insulin sensitivity (r = -0.38, P < 0.01).
      CONCLUSIONS: Correction of hyperglycaemia, independent of treatment modality,
      resulted in improvement of insulin resistance and decrease in sE-selectin levels.
      These changes might, in part, contribute to reduce the risk of diabetic
      microvascular and macrovascular complications in patients with Type 2 diabetes
      mellitus.

PMID- 11318845
TI  - The effect of diabetes and severe ischaemia on the penetration of ceftazidime
      into tissues of the limb.
AB  - AIMS: To determine the effect of diabetes and of different degrees of ischaemia
      on the penetration of ceftazidime into different tissues. METHODS: Sixteen
      patients (10 with diabetes mellitus) undergoing lower extremity amputation for
      severe ischaemia (in 12 in combination with infection), received 2000 mg
      ceftazidime intravenously as a bolus 30 min prior to the operation. Skin
      perfusion was determined by transcutaneous oxygen pressure measurements (TcPO2)
      on the dorsal side of the midfoot. After amputation bone, skin and muscle samples
      were obtained from the forefoot, midfoot and proximal tibia. Tissue and plasma
      concentrations were determined by HPLC. The tissue concentrations were corrected
      for blood contamination. RESULTS: No differences were observed in skin, muscle or
      bone ceftazidime levels between diabetic and non-diabetic patients. Multiple
      regression analysis suggested that tissue perfusion was a major determinant of
      skin and bone ceftazidime concentrations, predicting 40-47% of the ceftazidime
      concentrations at several biopsy sites. CONCLUSIONS: The present study suggests
      that tissue perfusion is the major determinant of the penetration of a third
      generation cephalosporin into the tissues of the ischaemic (diabetic) foot.
      Diabetes alone however, has no major effects upon this penetration.

PMID- 11318846
TI  - Prevalence and determinants of diabetes mellitus and glucose intolerance in a
      Canarian Caucasian population - comparison of the 1997 ADA and the 1985 WHO
      criteria. The Guia Study.
AB  - AIMS: To estimate the prevalence of diabetes mellitus, impaired fasting glucose
      and impaired glucose tolerance in a Canarian population according to the 1997 ADA
      and the 1985 WHO criteria; and to study the cardiovascular risk factors
      associated with these categories. METHODS: A total of 691 subjects over 30 years
      old were chosen in a random sampling of the population (stratified by age and
      sex). An oral glucose tolerance test was performed (excluding known diabetic
      patients) and lipids were determined in the fasting state. Anthropometric and
      blood pressure measurements were performed, and history of smoking habits and
      medications was recorded. RESULTS: The prevalence of diabetes was 15.9% (1997
      ADA) and 18.7% (1985 WHO); the prevalence of impaired fasting glucose and
      impaired glucose tolerance was 8.8 and 17.1%, respectively. The age-adjusted
      prevalence of diabetes (Segi's standard world population) for the population aged
      30-64 years was 12.4% (1985 WHO). The risk factors significantly associated with
      diabetes (1997 ADA and 1985 WHO) were age, body mass index; waist-to-hip ratio,
      systolic and mean blood pressure, triglycerides, total cholesterol and low HDL
      cholesterol. Age, body mass index and systolic blood pressure were associated
      with impaired fasting glucose and impaired glucose tolerance; triglycerides were
      also associated with impaired fasting glucose. CONCLUSIONS: The prevalence of
      diabetes mellitus and glucose intolerance in Guia is one of the highest among
      studied Caucasian populations. The new 1997 ADA criteria estimate a lower
      prevalence of diabetes. Impaired fasting glucose also had a lower prevalence than
      impaired glucose intolerance and the overlap of these categories was modest.

PMID- 11318847
TI  - Use of alternative medicines in diabetes mellitus.
AB  - AIMS: Enormous advances have been made in medical care but more people are still
      using herbal or alternative remedies. In chronic conditions such as diabetes
      patients may turn to alternative remedies that have been purported to improve
      glycaemic control. This study surveyed diabetic and control subjects about their
      use of all prescribed medication, over-the-counter supplements, and alternative
      medications. METHODS: Subjects were prospectively contacted in person or by
      telephone. Five hundred and two diabetic subjects and 201 control subjects were
      asked to provide details about themselves, their diabetes (for the diabetic
      subjects) and their use of prescribed medication, over-the-counter supplements
      and alternative medications. Subjects were asked to rank their assessment of the
      effectiveness of each medication. Costs were calculated on a per month basis from
      average prices obtained from five alternative health stores and five chemist
      shops. RESULTS: Of the diabetic subjects, 78% were taking prescribed medication
      for their diabetes, 44% were taking over-the-counter supplements and 31% were
      taking alternative medications. Of the control subjects, 63% were taking
      prescribed medication, 51% were taking over-the-counter supplements, and 37% were
      taking alternative medications. Multivitamins, vitamin E, vitamin C, calcium and
      aspirin were the most commonly used over the counter supplements. Garlic,
      echinacea, herbal mixtures, glucosamine were the most commonly used alternative
      medications. Chromium was used only by diabetic subjects and then only rarely.
      Subjects rated the effectiveness of the alternative medications significantly
      lower than for prescribed medications but still thought them efficacious.
      Alternative medications purported to have some hypoglycaemic effect were little
      used by diabetic subjects. Diabetic subjects spent almost as much money on over
      the-counter supplements and alternative medications together as they did on their
      diabetic medications. CONCLUSIONS: One-third of diabetic patients are taking
      alternative medications that they consider efficacious but this is no more than
      in the control group. The money spent on alternative and non-prescription
      supplements nearly equals that spent on prescription medications. In view of the
      money spent in this area the time is past due to evaluate these remedies and to
      establish what merit they have.

PMID- 11318848
TI  - Cancrum oris in a Caucasian male with Type 2 diabetes mellitus.
AB  - We describe a patient with Type 2 diabetes mellitus who developed cancrum oris
      requiring extensive oro-facial reconstructive surgery. There are no previous
      published reports of cancrum oris occurring in a Caucasian subject with no risk
      factors other than Type 2 diabetes.

PMID- 11318849
TI  - Diabetes and lipids - a conundrum.

PMID- 11318850
TI  - Dietary advice?

PMID- 11318871
TI  - Induction of CspA, an E. coli major cold-shock protein, upon nutritional upshift
      at 37 degrees C.
AB  - BACKGROUND: The synthesis of CspA, the major cold-shock protein of Escherichia
      coli, is dramatically induced upon cold shock. It was recently reported that
      there is massive presence of CspA under nonstress conditions, and it is thus
      claimed that CspA as the cold-shock protein is a misnomer. RESULTS: Here, we re
      examined and confirmed that CspA is induced upon culture dilution at 37 degrees
      C. However, its induction level is one-sixth of the cold-shock-induced level,
      clearly indicating that the major stress that induces CspA is cold shock. It was
      further found that CspA induction can be achieved not only by culture dilution
      but also by the simple addition of nutrients, and that it was almost completely
      abolished in the presence of rifampicin or nalidixic acid. Nutritional upshift
      causes the induction of only CspA but not other cold-shock-inducible CspA
      homologues. The amount of cspA mRNA rapidly and transiently increased by culture
      dilution, but its stability was not significantly changed. CONCLUSIONS: These
      results suggest that CspA is a nutritional-upshift stress protein as well as a
      cold-shock stress protein, and that CspA induction following nutritional upshift
      may be due to transcriptional activation.

PMID- 11318872
TI  - Sequence-specific termination by T7 RNA polymerase requires formation of paused
      conformation prior to the point of RNA release.
AB  - BACKGROUND: The sequence-specific, hairpin-independent termination signal for the
      bacteriophage RNA polymerases in Escherichia coli rrnB t1 terminator consists of
      two modules. The upstream module includes the conserved sequence and the
      downstream one is U-rich. RESULTS: Elongation complexes of T7 RNA polymerase
      paused 2 bp before reaching the termination site at a 500 microM concentration of
      NTP. At 5-50 microM NTP, however, they paused and terminated there or resumed
      elongation beyond the termination site. Only at higher concentrations of NTP (500
      microM), the pause complex proceeded slowly to and became incompetent at the
      termination site. At 4 bp or more before the termination site, the unprotected
      single-stranded region of transcription bubble shrank at the trailing edge to 4-5
      bp from approximately 10 bp, resulting from duplex formation of the conserved
      sequence. The pause and bubble collapse were not observed with an inactive mutant
      of the termination signal. CONCLUSION: Sequence-specific termination requires the
      slow elongation mode of paused conformation, working only at high concentrations
      of NTP for a few bp prior to the RNA release site. The collapse of bubble that
      was observed several base pairs before the termination site and/or the resulting
      duplex might subsequently lead to the paused conformation of T7 elongation
      complexes.

PMID- 11318873
TI  - Regulation of gene expression, cellular localization, and in vivo function of
      Caenorhabditis elegans DNA topoisomerase I.
AB  - BACKGROUND: DNA topoisomerase I is dispensable in yeast, but is essential during
      the embryogenesis of Drosophila and mouse. In order to determine functions of the
      enzyme in the development of Caenorhabditis elegans, phenotypes resulting from
      the deficiency were observed and correlated with the expression of the gene.
      RESULTS: The transcriptional regulation of the C. elegans DNA topoisomerase I
      gene was investigated by mRNA localization and reporter gene expression in C.
      elegans. The mRNA was expressed in the gonad and in the early embryos, followed
      by a rapid decrease in its level during the late embryonic stage. A reporter gene
      expression induced by the 5'-upstream DNA sequence appeared at the comma stage of
      embryos, continued through the L1 larval stage, and began to decrease gradually
      afterwards. The DNA topoisomerase I protein was immuno-localized in the nuclei of
      meiotic gonad cells and interphase embryonic cells, and unexpectedly in
      centrosomes of mitotic embryonic cells. Double-stranded RNA interference of DNA
      topoisomerase I gene expression resulted in pleiotropic phenotypes showing
      abnormal gonadogenesis, oocyte development and embryogenesis. CONCLUSION: These
      phenotypes, along with expressional regulations, demonstrate that DNA
      topoisomerase I plays important roles in rapidly growing germ cells and embryonic
      cells.

PMID- 11318874
TI  - Developmental roles and molecular characterization of a Drosophila homologue of
      Arabidopsis Argonaute1, the founder of a novel gene superfamily.
AB  - BACKGROUND: Arabidopsis Argonaute1 (AGO1) is the founder of a novel gene
      superfamily that is conserved from fission yeasts to humans. AGO1, and several
      other members of this superfamily are necessary for stem cell renewal or RNA
      interference. However, little has been reported about their roles in animal
      development or about the molecular activities of any of the members. RESULTS: We
      have isolated a Drosophila homologue of AGO1, dAGO1, in our attempt to search
      genetically for regulators of Wingless (Wg) signal transduction. dAGO1 is broadly
      expressed in the embryo and the imaginal disc. dAGO1 over-expression at wing
      margins suggested that it behaves as a positive regulator in the genetic
      background employed. Loss-of-function mutations of dAGO1, unexpectedly, did not
      give typical segment polarity phenotypes of the wg class; instead, dAGO1 maternal
      and zygotic mutant embryos showed developmental defects, with malformation of the
      nervous system being the most prominent. The mutant decreased in the numbers of
      several types of neurones and glia examined. The dAGO1 protein was distributed in
      the cytoplasm and co-sedimented with poly(U)- or poly(A)-conjugated beads.
      CONCLUSION: Our results suggest that the dAGO1 protein exerts its developmental
      functions by binding to RNA either directly or indirectly.

PMID- 11318875
TI  - Functional divergence of the TFL1-like gene family in Arabidopsis revealed by
      characterization of a novel homologue.
AB  - BACKGROUND: The TERMINAL FLOWER 1 (TFL1) gene of Arabidopsis plays an important
      role in regulating flowering time and in maintaining the fate of inflorescence
      meristem (IM). TFL1 is a homologue of CENTRORADIALIS (CEN) from Antirrhinum,
      which is only involved in IM maintenance. Recent mutational studies and the
      genome project revealed that TFL1 belongs to a small gene family in Arabidopsis,
      in which functional divergence may have occurred among the members. RESULTS: We
      found a new member of the TFL1 gene family, which is mapped on chromosome 2 of
      Arabidopsis. The predicted protein sequence encoded by this gene is more closely
      related to that of CEN than other Arabidopsis TFL1 homologues (and therefore
      named ATC for Arabidopsis thaliana CENTRORADIALIS homologue). Transgenic plants
      constitutively expressing the ATC gene (35S:ATC), in either wild-type or tfl1
      mutant backgrounds, showed a phenotype similar to that observed in transgenic
      plants constitutively expressing the TFL1 gene. However, in contrast to TFL1, the
      expression of ATC was only detected in the hypocotyl of young plants, and not in
      the IM. In addition, an atc loss-of-function mutant, isolated by screening a T
      DNA library, showed no phenotypes that were similar to those of tfl1 mutants.
      CONCLUSION: The phenotypes of transgenic plants over-expressing ATC suggest that
      the ATC protein can functionally substitute for TFL1. However, the pattern and
      level of expression and the loss-of-function phenotype indicate that ATC does not
      participate in the regulation of IM identity, but rather has a role that is
      different from that of TFL1.

PMID- 11318876
TI  - Down-regulation of alpha6 integrin, an anti-oncogene product, by functional
      cooperation of H-Ras and c-Myc.
AB  - BACKGROUND: The molecular basis of cooperation of H-Ras and c-Myc in regulating
      cellular behaviour, such as cell adhesiveness, is still poorly understood. To
      investigate the role of H-Ras and c-Myc in cell adhesiveness, a constitutively
      active H-RasV12 (H-RasV12) and c-Myc were stably expressed, singly or in
      combination in a haematopoietic cell line, and the expression and activity of
      cell adhesion molecules were monitored. RESULTS: We have shown that the ectopic
      expression of H-RasV12, but not c-Myc alone, in a haematopoietic cell line,
      induces the activation of very late antigen-6 (VLA-6, alpha6beta1) integrin. Co
      expression of H-RasV12 and c-Myc in the same cells further resulted in the
      induction of expression of vascular cell adhesion molecule-1 (VCAM-1) and the
      inhibition of expression of alpha6 integrin, a candidate anti-oncogene product,
      leading to a loss of adhesiveness to laminin (Lm), a ligand for VLA-6.
      CONCLUSIONS: Cooperation of H-Ras and c-Myc reciprocally regulates expression of
      the adhesion molecules, alpha6 integrin and VCAM-1. Our results represent an
      unprecedented account of the cooperation of the oncogene products, H-Ras and c
      Myc, to inhibit expression of an anti-oncogene product, alpha6 integrin.

PMID- 11318877
TI  - p48 subunit of mouse PTF1 binds to RBP-Jkappa/CBF-1, the intracellular mediator
      of Notch signalling, and is expressed in the neural tube of early stage embryos.
AB  - BACKGROUND: Development of the pancreas and the nervous tissues is regulated by
      common transcription factors. A basic helix-loop-helix protein, p48 of pancreas
      transcription factor 1 (PTF1), is essential for differentiation of the exocrine
      acinar cells. RESULTS: We isolated PTF1 p48 from 9.5-day mouse embryos as a
      binding protein of RBP-Jkappa, a mediator of Notch signalling. p48 bound to RBP
      Jkappa more strongly than and in a distinct way from Notch1. In 9.5-12.5 day
      embryos, p48 was expressed in the dorsal part of the neural tube as well as in
      the pancreatic buds. Two lines of evidence suggested functions of p48 in
      neurogenesis: (i) expression of p48 was induced in P19 cells when they committed
      to neural fate upon retinoic acid treatment, and (ii) p48 over-expressed in
      Xenopus embryos repressed the development of neuronal precursors. p48 inhibited
      the MASH1-activated transcription from the E-box, while p48 stimulated
      transcription from the PTF1 motif synergistically with E47. The p48/E47-activated
      transcription from the PTF1 motif was stimulated further by RBP-Jkappa and RBP
      Jkappa derivatives that mimicked the active RBP-Jkappa/Notch complex.
      CONCLUSIONS: In developing embryos, p48 is expressed in both the nervous system
      and the pancreas. p48 inhibits neuronal differentiation. We propose possible
      mechanisms for this inhibition.

PMID- 11318878
TI  - Defective development of secretory neurones in the hypothalamus of Arnt2-knockout
      mice.
AB  - BACKGROUND: Within the basic region-helix-loop-helix (bHLH)-PAS family of
      transcription factors, Arnt and Arnt2 play unique roles; these two factors not
      only heterodimerize with themselves, but also with other members of this family
      and they act as transcription regulators which bind to specific DNA elements.
      Whereas Arnt is broadly expressed in various tissues, the expression of Arnt2 is
      known to be limited to the neural tissues. RESULTS: To elucidate the function of
      Arnt2 in detail, we cloned the mouse Arnt2 gene and its gene structure was
      determined. We subsequently generated germ line Arnt2 mutant mice by gene
      targeting technology. Heterozygous Arnt2 mice were viable, but homozygous Arnt2
      gene knockout mice died shortly after birth. Histological and immunological
      analyses revealed that the supraoptic nuclei (SON) and the paraventricular nuclei
      (PVN) are hypocellular. Moreover, secretory neurones identified by the expression
      of neurosecretory hormone such as arginine vasopressin, oxytocin, corticotrophin
      releasing hormone and somatostatin are completely absent in SON and PVN in the
      mutant Arnt2 mice. Consistent with these observations, prospective SON and PVN
      neurones which express Brn2 appeared around E13.5 in the mantle zone, but no
      neurones which expressed the neurosecretory hormones were found in the SON and
      PVN regions. CONCLUSIONS: These data show that the transcription factor Arnt2
      controls the development of the secretory neurones at the later or final stages
      of differentiation rather than at the beginning stage. Strikingly similar
      observations have been reported with the Sim1 deficient mice. Taken together, our
      results demonstrate that Arnt2 is an indispensable transcription factor for the
      development of the hypothalamus, and suggest that Arnt2 is an obligatory partner
      molecule of Sim1 in the developmental process of the neuroendocrinological cell
      lineages.

PMID- 11318879
TI  - Induction of IRF-3/-7 kinase and NF-kappaB in response to double-stranded RNA and
      virus infection: common and unique pathways.
AB  - BACKGROUND: Infection by virus or treatment with double-stranded RNA (dsRNA)
      results in the activation of transcription factors including IRF-3, IRF-7 and a
      pleiotropic regulator NF-kappaB by specific phosphorylation. These factors are
      important in triggering a cascade of antiviral responses. A protein kinase that
      is yet to be identified is responsible for the activation of these factors and
      plays a key role in the responses. RESULTS: The signal cascade was analysed using
      sensitive assays for the activation of IRF-3 and NF-kappaB, and various
      inhibitors. We found that the activation of IRF-3 and NF-kappaB by dsRNA or virus
      involves a process that is sensitive to Geldanamycin. Although the induction of
      NF-kappaB by dsRNA/virus and TNF-alpha involves common downstream pathways
      including IKK activation, the upstream, Geldanamycin-sensitive process was unique
      to the dsRNA/virus-induced signal. By an in vitro assay using cell extract, we
      found an inducible protein kinase activity with physiological specificity of IRF
      3 phosphorylation. Furthermore, the same extract specifically phosphorylated IRF
      7 in a similar manner. CONCLUSIONS: Double-stranded RNA or virus triggers a
      specific signal cascade that results in the activation of the IRF-3/-7 kinase we
      detected, which corresponds to the long-sought signalling machinery that is
      responsible for triggering the early phase of innate response. The signal
      branches to a common NF-kappaB activation cascade, thus resulting in the
      activation of a set of critical transcription factors for the response.

PMID- 11318880
TI  - Information about migraine disability influences physicians' perceptions of
      illness severity and treatment needs.
AB  - OBJECTIVE: To assess physician-patient communication about headache-related
      disability and to evaluate the influence of information about disability on
      physicians' perceptions of illness severity and the treatment needs of
      migraineurs. BACKGROUND: Evidence suggests that migraine is suboptimally treated
      in clinical practice, partly due to poor communication between physicians and
      their patients. METHODS: One hundred five neurologists and primary care
      physicians with an interest in headache participated in two interactive surveys,
      one in North America (n=42) and one in Europe (n=63). Each survey focused on the
      evaluation of four videotaped migraine cases. The first case was evaluated twice,
      initially after a typical symptom history that centered on diagnosis and then
      following a fuller history of migraine disability. Additional questions assessed
      the extent of the collection of migraine disability information in clinical
      practice. RESULTS: Physicians reported that they recorded symptoms relating to
      diagnosis (eg, pain location/intensity, associated symptoms) rather than
      information on headache-related disability. Only about one third of patients
      volunteered disability information. When made available to them, physicians rated
      information on disability as one of the most important factors in assessing
      treatment needs. In particular, when physicians knew the patient's disability
      history: (1) the proportion of physicians who rated the patient's illness as
      "severe" increased by 128% in North America, 27% in Europe; (2) the proportion of
      physicians who recommended immediate treatment increased by 63% in North America,
      37% in Europe; and (3) the proportion of patients recommended for a follow-up
      visit increased by 15% in North America, 18% in Europe. CONCLUSIONS: Physicians
      and patients often fail to discuss headache-related disability during
      consultation. This information has a powerful influence on physicians'
      perceptions of illness severity, treatment choice, and the need for follow-up.
      Tools to improve communication about headache-related disability, such as the
      Migraine Disability Assessment questionnaire, may favorably improve migraine
      management.

PMID- 11318881
TI  - Delivery outcome in women who used drugs for migraine during pregnancy with
      special reference to sumatriptan.
AB  - OBJECTIVE: To evaluate delivery outcome in women who used drugs for migraine
      during pregnancy with special reference to sumatriptan. BACKGROUND: The safety of
      the use of drugs for migraine during pregnancy is not established. DESIGN AND
      METHODS: Using the Swedish Medical Birth Registry which contains information on
      drug use reported by women at the first antenatal visit, 912 infants (born in 905
      deliveries) whose mothers had used drugs for migraine were identified, the
      majority of whom (n = 658) had used sumatriptan. RESULTS: These women differed
      from the general population of women who had delivered by being older and more
      often of first parity, but they had similar smoking habits. Slightly more often,
      the infants were preterm, and they had a birth weight less than 2500 g; neither
      of these effects were statistically significant. There seemed to be no difference
      between infants exposed to sumatriptan and those exposed to other drugs used for
      migraine. No increase in the rate of congenital malformations was seen.
      CONCLUSIONS: The data indicate that use of sumatriptan in early pregnancy does
      not result in a large increase in teratogenic risk, but do not rule out the
      possibility of a moderate increase in risk for a specific birth defect.

PMID- 11318882
TI  - An open-label dose-titration study of the efficacy and tolerability of tizanidine
      hydrochloride tablets in the prophylaxis of chronic daily headache.
AB  - OBJECTIVE: To assess effectiveness and safety of tizanidine hydrochloride tablets
      for the prophylaxis of chronic daily headache. BACKGROUND: Tizanidine
      hydrochloride is an alpha2-adrenergic agonist that inhibits the release and
      effectiveness of norepinephrine at both central sites (eg, the locus ceruleus)
      and the spinal cord. It acts as a central muscle relaxant and has antinociceptive
      effects. Preliminary research and retrospective analyses have suggested efficacy
      in treatment of both chronic tension-type headache and chronic daily headache
      with migrainous features. DESIGN: Thirty-nine patients with more than 15 headache
      days per month (33 with migraine, 5 migrainous, 1 chronic tension-type) completed
      a 4-week baseline, with 31 completing a planned 12 weeks of treatment with
      tizanidine. Dosing was titrated from 2 mg at bedtime to a median daily dose of 14
      mg (mean, 13.5; SD, 4.3; range, 4 to 20, divided over three doses per day) by
      treatment week 4. RESULTS: The overall headache index through week 12 (headache
      frequency x average intensity x duration) declined significantly (P<.00000002),
      with a corresponding increase in mean percentage improvement from 49% for weeks 1
      through 4, to 65% for weeks 5 through 8, and 64% for weeks 9 through 12
      (P<.0182). During weeks 9 through 12, 67% had improved more than 50% compared to
      baseline. Overall headache frequency declined from 22.83 to 15.83 days per month
      (P<.00001), with frequency of severe headaches dropping from 7.52 to 3.58 days
      per month (P<.000035). Average headache intensity dropped from 1.83 to 1.07 (1-to
      5 scale), peak intensity declined from 2.37 to 1.40, and mean duration was
      reduced from 6.96 to 4.00 hours per headache (P<.00001). Improvement also
      occurred on visual analog scales of overall headache status, mood, sleep, quality
      of life (P<.00001), and sexual function (P<.0075); as well as the Beck Depression
      Inventory-II (P<.00073). Mild-to-moderate adverse events reported by more than
      10% of the patients included somnolence, asthenia, and dry mouth. Only 3 patients
      discontinued treatment due to adverse events: somnolence and dry mouth alone (n =
      1), or in combination with either hyperkinesis (n = 1) or constipation (n = 1).
      One patient had elevated liver enzymes that returned to normal after the drug was
      discontinued. CONCLUSIONS: The results provide preliminary support for the
      efficacy, safety, and tolerability of tizanidine in the prophylaxis of chronic
      daily headache.

PMID- 11318883
TI  - Consumer views on management of trigeminal neuralgia.
AB  - OBJECTIVE: To assess consumers' views on treatments used for trigeminal neuralgia
      and to compare their assessments with those of clinicians. METHODS: A short self
      administered questionnaire was distributed to 133 individuals with trigeminal
      neuralgia and 21 clinicians attending national support group meetings in the
      United States and United Kingdom. RESULTS: Responses were obtained from 82% of
      those with trigeminal neuralgia and from 50% of the clinicians. All sufferers had
      used medical therapies (mean of three drugs), and 40% to 50% had undergone
      surgical treatment. All of the attendees with trigeminal neuralgia reported at
      least one side effect (mean +/- SD, 4.9 +/- 1.8). The clinicians underestimated
      the number of side effects, but both groups agreed that drowsiness and cognitive
      impairment are side effects that are particularly disliked. The mean current
      quality-of-life score, measured on a scale of 1 to 5 (5 = worse), was 2.7 +/-
      1.5. Only 37% of sufferers gave an opinion as to the best form of treatment.
      CONCLUSIONS: Therapy leads to side effects which tend to be underestimated by
      clinicians. Patients currently find it difficult to make decisions about
      treatment. More collaborative research with active involvement of sufferers would
      improve the evidence base on which decisions can be made.

PMID- 11318884
TI  - Sumatriptan nasal spray and cognitive function during migraine: results of an
      open-label study.
AB  - OBJECTIVE: To examine measures of cognitive function during acute migraine,
      before and after treatment with sumatriptan nasal spray, 20 mg. BACKGROUND:
      Migraineurs frequently report symptoms of cognitive impairment during migraine.
      The efficacy of sumatriptan for treatment of migraine-related cognitive
      impairment is undocumented. METHODS: This open-label, single-attack study of 28
      subjects used the Headache Care Center-Automated Neuropsychological Assessment
      Metrics, a computerized neuropsychological assessment battery, to measure
      cognitive function under three patient conditions: migraine-free, untreated
      migraine, and following sumatriptan (primary outcome). Headache response and pain
      free response, percent effectiveness, and clinical disability were measured.
      RESULTS: Cognitive function (simple reaction time, sustained
      attention/concentration, working memory, visual-spatial processing) and
      alertness/fatigue were adversely affected during migraine compared with migraine
      free performance (P<.05), and rapidly restored following sumatriptan nasal spray,
      20 mg (P<.05). Headache and pain-free response were 86% and 68%, respectively, at
      135 minutes postdose. Changes in migraine pain severity, clinical disability, and
      percent effectiveness following treatment with sumatriptan nasal spray, 20 mg,
      were significantly correlated with cognitive function measures across all
      subtests (P<.001). CONCLUSIONS: Sumatriptan nasal spray, 20 mg, restored migraine
      related cognitive function and clinical disability.

PMID- 11318885
TI  - Use of atraumatic spinal needles among neurologists in the United States.
AB  - OBJECTIVE: To evaluate atraumatic spinal needle use among US neurologists.
      BACKGROUND: Postdural puncture headache following lumbar puncture may be
      dramatically reduced through the use of atraumatic pencil-point spinal needles.
      It was hypothesized that atraumatic spinal needles are rarely used by members of
      specialties outside of anesthesiology. To determine the extent to which
      atraumatic spinal needles are currently being used for lumbar puncture in the
      United States, American neurologists (one group of physicians who regularly
      perform lumbar punctures) were surveyed. METHODS: A questionnaire was mailed to
      all 7798 members of the American Academy of Neurology listed in the membership
      directory. The questionnaire included items pertaining to age, practice setting,
      knowledge of pencil-point (atraumatic) spinal needles, and lumbar puncture
      practices. RESULTS: Only a fraction (2%) of the neurologists surveyed routinely
      use atraumatic spinal needles. Almost half of the responding neurologists
      reported having no knowledge of pencil-point spinal needles. Among those who did
      have knowledge of these new spinal needles, the most common reasons given for not
      using them were nonavailability and expense. CONCLUSIONS: Atraumatic spinal
      needles for lumbar puncture have been shown to dramatically decrease the risk of
      postdural puncture headache. Although the use of these needles is standard
      practice among anesthesiologists, they have not been adopted by other medical
      specialties. This may lead to unnecessary morbidity among patients undergoing
      lumbar puncture.

PMID- 11318886
TI  - Comparative study of a combination of isometheptene mucate, dichloralphenazone
      with acetaminophen and sumatriptan succinate in the treatment of migraine.
AB  - OBJECTIVE: To compare the safety and efficacy of isometheptene mucate,
      dichloralphenazone with acetaminophen to sumatriptan succinate for the treatment
      of mild-to-moderate migraine, with or without aura, when taken at the first sign
      of an attack. BACKGROUND: The Food and Drug Administration approved sumatriptan
      succinate and the combination of isometheptene mucate, dichloralphenazone with
      acetaminophen for the treatment of migraine. As part of the stratified treatment
      of migraine, those patients whose headaches are mild or moderate may benefit from
      nontriptan medications. Additionally, early treatment of acute migraine before
      the headache has become moderate or severe may improve response to treatment.
      METHODS: This was a multicenter, double-blind, randomized, parallel-group study
      to assess the safety and efficacy of the combination of isometheptene mucate,
      dichloralphenazone with acetaminophen and sumatriptan succinate in the early
      stages of a single migraine attack. Patients diagnosed with migraine, with or
      without aura, as defined by the International Headache Society diagnostic
      criteria were enrolled. RESULTS: One hundred thirty-seven patients were enrolled
      in the study. Data for efficacy were available for 126 patients; safety data were
      available for 128 patients. No statistically significant difference between the
      two active agents in the patient's response to treatment was demonstrated.
      Headache recurrence was not significantly different over the 24-hour evaluation
      period for those patients responding in the first 4 hours. In those with headache
      recurrence, it was statistically significantly more severe in those patients
      treated with sumatriptan succinate. Improvement in functional disability was, in
      general, better among those treated with isometheptene mucate, dichloralphenazone
      with acetaminophen. Global analysis of efficacy was similar in the two active
      groups. Patients treated with sumatriptan succinate were somewhat more likely to
      have adverse effects than the isometheptene mucate, dichloralphenazone with
      acetaminophen group. CONCLUSIONS: Both isometheptene mucate, dichloralphenazone
      with acetaminophen and sumatriptan succinate are safe and effective when used
      early in the treatment of an acute migraine. Several parameters suggest that
      isometheptene mucate, dichloralphenazone with acetaminophen may have a slight
      advantage compared with sumatriptan succinate in the early treatment of mild-to
      moderate migraine.

PMID- 11318887
TI  - A history of migraine is not a risk factor to develop an ischemic stroke in the
      elderly.
AB  - OBJECTIVE: To assess the prevalence of migraine in elderly patients hospitalized
      with ischemic stroke compared with vascular and nonvascular control groups.
      BACKGROUND: Migraine is a disease with a presumed vascular mechanism. While
      migraine is a common complaint of young victims of ischemic stroke, it is unclear
      whether a current or past history of migraine constitutes a risk factor for
      developing an ischemic stroke in the elderly. METHODS: We obtained current and
      past headache history from 100 consecutive patients hospitalized with ischemic
      stroke (aged 60 years or older) and compared the results with 100 patients
      hospitalized due to acute myocardial infarction and 100 hospitalized patients
      with no vascular disease. RESULTS: The sex and the age of the patients did not
      differ among the groups. The lifetime prevalence of migraine (8% of the patients
      with ischemic stroke, 8% of the nonvascular controls, and 15% of the patients
      with acute myocardial infarction) or of all types of headaches (27%, 30%, and
      15%, respectively), did not differ significantly between the groups. CONCLUSIONS:
      Based on the reported history, elderly migraineurs are not at increased risk to
      develop ischemic stroke.

PMID- 11318888
TI  - Development and validation of the Headache Needs Assessment (HANA) survey.
AB  - OBJECTIVE: To develop and validate a brief survey of migraine-related quality-of
      life issues. The Headache Needs Assessment (HANA) questionnaire was designed to
      assess two dimensions of the chronic impact of migraine (frequency and
      bothersomeness). METHODS: Seven issues related to living with migraine were posed
      as ratings of frequency and bothersomeness. Validation studies were performed in
      a Web-based survey, a clinical trial responsiveness population, and a retest
      reliability population. Headache characteristics (eg, frequency, severity, and
      treatment), demographic information, and the Headache Disability Inventory were
      used for external validation. RESULTS: The HANA was completed in full by 994
      adults in the Web survey, with a mean total score of 77.98 +/- 40.49 (range, 7 to
      175). There were no floor or ceiling effects. The HANA met the standards for
      validity with internal consistency reliability (Cronbach alpha =.92, eigenvalue
      for the single factor = 4.8, and test-retest reliability = 0.77). External
      validity showed a high correlation between HANA and Headache Disability Inventory
      total scores (0.73, P<.0001), and high correlations with disease and treatment
      characteristics. CONCLUSIONS: These data demonstrate the psychometric properties
      of the HANA. The brief questionnaire may be a useful screening tool to evaluate
      the impact of migraine on individuals. The two-dimensional approach to patient
      reported quality of life allows individuals to weight the impact of both
      frequency and bothersomeness of chronic migraines on multiple aspects of daily
      life.

PMID- 11318889
TI  - Migraine with aura after intracranial endovascular procedures.
AB  - OBJECTIVE: To describe three cases of migraine (two with aura) after an
      intracranial endovascular procedure. Method.-Retrospective. RESULTS: One patient
      had an attack of migraine with prolonged aura after embolization of a dural
      arteriovenous fistula. Another patient had an attack of migraine with aura (and
      hemiparesis) after a diagnostic angiogram. The third patient already suffered
      from migraine with aura and had a migraine attack after embolization of an
      occipital arteriovenous malformation. A quadrantanopia persisted in this patient.
      Outcome of the other two patients was good. CONCLUSION: Intracranial endovascular
      procedures can induce migraine with aura. We could not identify the underlying
      pathophysiological mechanism, but mechanical, chemical, immunological, or
      hemodynamic factors could be involved.

PMID- 11318890
TI  - Migraine aura without headache versus transient ischemic attack during pregnancy.

PMID- 11318891
TI  - Pseudo-pseudotumor cerebri.

PMID- 11318892
TI  - Additional thoughts about racial differences in the prevalence of headaches in US
      adolescents.

PMID- 11318893
TI  - Presentation of migraine as odontalgia.

PMID- 11318894
TI  - Pathology of lymphoma progression.
AB  - Reflecting the stepwise process of oncogenesis, lymphomas may cumulatively
      develop a more aggressive phenotype during the course of disease, a process
      referred to as lymphoma progression. Although morphological, clinical and
      biological aspects of lymphoma progression do not always overlap, changes in
      lymphoma morphology frequently indicate alterations in the clinical and
      biological behaviour of the disease. Indolent and aggressive lymphomas in disease
      progression can either be clonally related or represent clonally unrelated
      neoplasms. We propose to use the term 'lymphoma progression' in a biological
      sense denoting only clonal development of and within a lymphoma entity. The term
      'composite lymphoma' should be used as a merely descriptive morphological
      designation for different lymphoma entities in one individual irrespective of
      clonal relationship. Many types of aggressive B-cell non-Hodgkin's lymphomas and
      Hodgkin's lymphomas are reported to secondarily develop in lymphoma progression.
      Genetic changes associated with lymphoma progression frequently abrogate the
      differentiating effects of alterations occurring in indolent lymphomas, leading
      to increased cell proliferation. Within different lymphoma entities, high-risk
      disease variants mimicking lymphoma progression exist.

PMID- 11318895
TI  - The utility of cytokeratin subsets in distinguishing Barrett's-related
      oesophageal adenocarcinoma from gastric adenocarcinoma.
AB  - AIMS: Accurate tumour classification is critical for meaningful epidemiological
      studies in the assessment of cancer incidence rates and trends. Differentiating
      primary gastric carcinoma from oesophageal carcinoma can be difficult, especially
      when tumours are large and involve both the oesophagus and stomach. Furthermore,
      adenocarcinomas of both organs typically are of intestinal histological type and
      arise in a background of intestinal metaplasia. Consequently, histological
      markers that reliably distinguish Barrett's-related oesophageal adenocarcinoma
      from gastric adenocarcinoma would be useful. Cytokeratins (CK)7 and 20 are
      cytoplasmic structural proteins with restricted expression that help to determine
      the origin of many epithelial tumours including those of the gastrointestinal
      tract. The aim of this study was to determine the utility of co-ordinate CK7 and
      20 expression in the distinction of Barrett's-related oesophageal adenocarcinoma
      from gastric adenocarcinoma arising in a background of intestinal metaplasia.
      METHODS AND RESULTS: CK7 and 20 immunostaining was performed on randomly selected
      surgical resection specimens from patients with Barrett's-related oesophageal
      adenocarcinoma (n = 30) and intestinal type gastric adenocarcinoma (n = 14)
      arising in a background of intestinal metaplasia. A CK7+ CK20- immunophenotype
      was demonstrated in 27 of 30 (90%) patients with Barrett's-related oesophageal
      adenocarcinoma and only three of 14 (21%) gastric adenocarcinomas. The
      sensitivity, specificity and positive predictive value of a CK7+/20-
      immunophenotype for a diagnosis of Barrett's-related oesophageal adenocarcinoma
      was 90%, 79%, and 90%, respectively. CONCLUSIONS: A CK7+/20- tumour
      immunophenotype is associated with Barrett's-related oesophageal adenocarcinoma
      and may be useful in accurate tumour classification, thus facilitating improving
      epidemiological evaluation of tumours at the oesophagogastric junction.

PMID- 11318896
TI  - Use of calretinin in the differential diagnosis of unicystic ameloblastomas.
AB  - AIMS: Calretinin, a 29-kDa calcium-binding protein is expressed widely in normal
      human tissues and tumours including both unicystic and solid and multicystic
      ameloblastomas. The histological distinction between unicystic ameloblastomas and
      certain non-neoplastic odontogenic cysts can be problematic. The objective of
      this study was to determine whether calretinin was expressed in the lining
      epithelium of odontogenic keratocysts, residual and dentigerous cysts and to
      determine whether this calcium-binding protein could be used to distinguish these
      cysts from the unicystic ameloblastoma. METHODS AND RESULTS: The lining
      epithelium in 22 cases of odontogenic keratocyst, 26 cases of residual cyst and
      20 cases of dentigerous cyst were examined for the expression of calretinin. No
      positive epithelial staining was observed in any of these cystic lesions. In
      comparison, however, 81.5% of cases of unicystic ameloblastoma showed a coarse
      dark brown staining of the more superficial epithelial cell layers. Scattered
      positive stromal and epithelial cells were present; these were interpreted as
      mast cells. CONCLUSIONS: Calretinin appears to be a specific immunohistochemical
      marker for neoplastic ameloblastic epithelium and we suggest that it may be an
      important diagnostic aid in the differential diagnosis of cystic odontogenic
      lesions and ameloblastic tumours.

PMID- 11318897
TI  - Ultrastructural examination is essential for diagnosis of papillary meningioma.
AB  - AIMS: Papillary meningioma is a rare meningeal tumour. To date only a few cases
      have been reported and their immunohistochemical features have not been fully
      documented. METHODS AND RESULTS: A 49-year-old woman presented with a 2-month
      history of headaches and memory disturbance. CT and MRI imaging showed an
      enhancing pineal mass with extension into the occipital lobes and invasion of the
      splenium. At surgery, the tumour was found to be tough and vascular with a well
      defined capsule. No recurrence was noted 19 months after the operation. In
      another case a 44-year-old woman was admitted with 1-month history of headaches,
      poor memory, imbalance and diplopia. CT scan showed a large hyperdense,
      uniformly, enhancing mass within the middle cranial fossa at the petrous ridge.
      The tumour recurred 19 and 25 months after first resection. The histology of both
      tumours was similar. The neoplasms contained polygonal cells with a moderate
      amount of cytoplasm, rounded regular nuclei and distinct cell borders. The cells
      were arranged radially around the blood vessels (perivascular pattern) and a
      papillary pattern was seen only focally. Mitotic figures were moderately
      frequent. Immunohistochemistry showed that both tumours were immunoreactive to
      vimentin and NSE, whereas GFAP, CAM5.2, EMA, S100 protein and synaptophysin were
      negative. Electron microscopy revealed interdigitating cell processes, desmosomes
      and intermediate filaments. CONCLUSIONS: The histological and immunohistochemical
      features of these two tumours are complex and difficult to interpret. Although
      papillary meningiomas were considered in our initial differential diagnosis, the
      final conclusion was possible only when the ultrastructural features were
      revealed.

PMID- 11318898
TI  - Different roles of arteriosclerosis in the rupture of intracranial dissecting
      aneurysms.
AB  - AIMS: Although intracranial dissecting aneurysm (IDA) is a newly described
      variant of the brain aneurysms that affects mainly the vertebrobasilar arterial
      system, its pathogenesis remains obscure. We aimed to clarify the role of
      arteriosclerosis in the pathogenesis of IDA based on histopathological findings
      in seven autopsy cases of IDA. METHODS AND RESULTS: All cases exhibited systemic
      hypertension or left ventricular hypertrophy. Macroscopically, all cases
      exhibited subarachnoid haemorrhage. Two types of dissection were recognized in
      the vertebral artery. Six of seven IDA cases showed a widespread disruption of
      the entire thickness of the arterial wall with the formation of a dilated
      pseudoaneurysm, which consisted of thin adventitia (arterial wall disruption
      type). Medial disruption of the arterial wall and subadventitial dissecting
      haemorrhage were also found, resulting in the formation of a false lumen and
      stenosis of the 'true' lumen of the artery. However, these lesions were connected
      to the site of rupture of the entire arterial wall. Within 1 day after onset of
      IDA, the autopsy cases showed formation of fibrin thrombus, marked leucocyte
      infiltration and necrosis of the arterial wall at the site of the lesion. Cases
      that survived more than 1 week showed smooth muscle cell proliferation,
      macrophage accumulation and lymphocytic infiltration in the lesions. These cases
      showed no atherosclerotic plaque, but non-atherosclerotic fibrocellular intima.
      The thickness of intima and media was significantly less in the vertebral artery
      of IDA patients than that of non-IDA patients with systemic hypertension. On the
      other hand, the remaining case showed severe atherosclerosis with haemorrhage
      into the lipid core without connection to the arterial lumen (intra-atheromatous
      plaque haemorrhage type). However, unusual arterioles and neovascularization of
      the intra-and peri-arterial walls were observed. CONCLUSIONS: Our results suggest
      that disruption of the entire arterial wall may be a critical event in the
      development of IDA and result in the medial disruption and subadventitial
      haemorrhage. Non-atheromatous intima might function as a protective factor in
      arterial wall disruption. On the other hand, atherosclerosis may predispose to
      intra-atheromatous plaque haemorrhage type of IDA through intramural haemorrhage
      originating from the newly formed vessels.

PMID- 11318899
TI  - Myocardial fibrosis assessment by semiquantitative, point-counting and computer
      based methods in patients with heart muscle disease: a comparative study.
AB  - AIMS: No study has directly compared different histomorphometric methods of
      quantification of myocardial fibrosis. Therefore we compared the results of
      semiquantitative, point-counting and computer-based methods in the assessement of
      myocardial fibrosis in a consecutive series of endomyocardial biopsy samples from
      patients with heart muscle disease. METHODS AND RESULTS: Histological samples (at
      least three per patient) were obtained by endomyocardial biopsy from 11 patients
      with focal myocarditis and from 24 ambulatory patients with idiopathic dilated
      cardiomyopathy, or during surgery in 10 patients who underwent partial left
      ventriculectomy. Samples were cut and stained with Masson-trichrome for better
      contrast. From each sample, a representative field was digitized, and the amount
      of fibrosis was assessed by semiquantitative scoring, by point-counting, and by
      computer-based software. Semiquantitative scoring correlated with both point
      counting (Spearman's r = 0.69, P < 0.0001) and computer-based (Spearman's r =
      0.83, P < 0.0001) methods. There was also a good correlation between point
      counting and computer-based methods (r = 0.71, P < 0.0001). However, when
      compared with the point-counting method, the computer-based method overestimated
      percent fibrosis by 3.0 +/- 6.7% (P = 0.004). This overestimation correlated with
      the mean percent fibrosis (r = 0.38, P = 0.014). CONCLUSIONS: Our data show good
      correlations between the three methods of myocardial fibrosis assessment.
      However, systematic differences between them emphasize that this should be taken
      into consideration when comparing results of the studies using different methods
      of fibrosis assessment.

PMID- 11318900
TI  - Dirofilariasis due to Dirofilaria repens in Italy, an emergent zoonosis: report
      of 60 new cases.
AB  - AIMS: Sixty new cases of human dirofilariasis due to Dirofilaria repens,
      occurring in Italy between 1990 and 1999, are presented. This is the most
      extensive case study of this zoonosis reported worldwide by a single study group.
      The aim is to utilize this large experience to characterize the different
      histopathological findings in the parasitic lesions in man. METHODS AND RESULTS:
      Diagnosis was performed on histological sections of the nematode enclosed in the
      nodules excised at biopsy or surgery. The nematode was located in the
      subcutaneous tissue (49 cases), the epididymis (two cases), the spermatic cord
      (two cases), the lung (two cases), the breast (two cases), the omentum (two
      cases) and under the conjunctival tissue (one case). The majority of cases (46)
      were from Piedmont; the remainder were from Emilia-Romagna, Sardinia, Sicily,
      Tuscany, Apulia and Lombardy. The histopathological features of the lesions are
      described and the clinical and epidemiological aspects of the zoonosis are
      discussed. The prevalence in Italy in general and in the area of Piedmont in
      particular, comprising the provinces of Alessandria, Asti, Novara and Vercelli,
      which is one of the most severely affected areas of the world, is emphasized. The
      evident increase in the number of cases in the last few years is a clear
      indication that it is an emergent zoonosis. CONCLUSIONS: We recommend that each
      and every case observed be recorded, to enable the true extent of human
      dirofilariasis in Italy to be assessed, and that a reference centre be set up in
      the area to collate the data. The importance of the histopathologist's role in
      the diagnosis is stressed.

PMID- 11318901
TI  - Extremely high Langerhans cell infiltration contributes to the favourable
      prognosis of HPV-infected squamous cell carcinoma and adenocarcinoma of the lung.
AB  - AIMS: The infiltration of Langerhans cells in adenocarcinomas and squamous cell
      carcinomas of the lung was examined in relation to prognostic implications and
      human papillomavirus (HPV) infection. METHODS AND RESULTS: Samples from 62
      adenocarcinoma and 59 squamous cell carcinoma patients in 1995-97, the prognosis
      of which had been followed up, were used. The Langerhans cells were demonstrated
      immunohistochemically using anti S100a and CD1 antibodies. Human papillomavirus
      (HPV) infection was examined by polymerase chain reaction (PCR) and nonisotopic
      in-situ hybridization (NISH) methods. Statistical analysis was carried out using
      the Kaplan-Meier method (Wilcoxon analysis) and multiple regression analysis. HPV
      infection was demonstrated in 12 cases (19.4%) of adenocarcinoma. The HPV
      infected adenocarcinomas had abundant faintly eosinophilic cytoplasm, and were
      immunohistochemically positive for the surfactant apoprotein A. In the 59 cases
      of squamous cell carcinomas 19 were of the well differentiated form, and 29 and
      11 were moderately and poorly differentiated cases, respectively. HPV was
      detected in 29 cases (49.2%) (13 well and 16 moderately differentiated cases). In
      all HPV-infected adenocarcinoma and squamous cell carcinoma cases, extremely
      large numbers of Langerhans cells (more than 100 per high-power field) were
      demonstrated in the tumour nests. In contrast, in the non-HPV-infected
      adenocarcinomas and squamous cell carcinomas, only a few (less than about 10 per
      high-power field) Langerhans cells were observed. The squamous cell carcinoma
      cases with high Langerhans cell infiltration, which were also infected with HPV,
      showed a significantly good prognosis (P = 0.007). The adenocarcinoma cases with
      high Langerhans cell infiltration tended to have a better prognosis than the
      cases with low Langerhans cell infiltration, but the difference was not
      statistically significant. The low number of highly infiltrated cases was
      insufficient for an adequate statistical analysis. Furthermore, there was no
      significant correlation between either Langerhans cell infiltration and smoking,
      or HPV infection and smoking, in either squamous cell carcinoma or adenocarcinoma
      cases. CONCLUSIONS: It was considered that the extremely high Langerhans cell
      infiltration in the tumours was caused by HPV infection. The extremely large
      number of Langerhans cells in the tumours contributes to the favourable prognosis
      for HPV-infected lung cancer.

PMID- 11318903
TI  - Websites review-pathology images.

PMID- 11318902
TI  - Interleukin-13 and interleukin-13 receptor in Hodgkin's disease: possible
      autocrine mechanism and involvement in fibrosis.
AB  - AIMS: Hodgkin's disease (HD) is characterized by the presence of Hodgkin and Reed
      Sternberg (H-RS) cells against a hyperplastic background of reactive cells such
      as lymphocytes, histiocytes, plasma cells, eosinophils, neutrophils, and stromal
      cells. There is ample evidence to suggest that proliferation and survival of HD
      derived cells is due to cytokine signalling. Recently, high expression of
      interleukin (IL)-13 was described in HD-derived cell lines. Here we investigated
      the possible involvement of IL-13 in the pathophysiology, especially autocrine
      pathways of H-RS cells. METHODS AND RESULTS: The expression of IL-13 and IL-13
      receptor (IL-13R) was determined by immunostaining and reverse transcriptase
      polymerase chain reaction in 39 cases of HD, including 17 cases with nodular
      sclerosis (NS) type, 19 cases with mixed cellularity (MC), and three cases with
      lymphocyte predominance (LP) type. Expression of IL-13 was confined to H-RS cells
      and a few lymphocytes. IL-13R was expressed in H-RS cells, lymphocytes,
      histiocytes, fibroblasts, and endothelial cells. H-RS cells of MC and NS types
      frequently expressed both IL-13 and IL-13R. However, the number of IL-13-positive
      H-RS cells was statistically higher in NS-type than in MC-type, but the number of
      IL-13R was similar. IL-13R-positive fibroblasts were frequently encountered in NS
      type. H-RS cells of LP type rarely expressed IL-13. CONCLUSIONS: Our results
      suggest that IL-13 might be involved in autocrine pathways of H-RS cells and
      fibrosis at least in NS-type. Our results also indicated that in addition to the
      morphological and phenotypic differences, the neoplastic cells of LP type might
      be functionally different from H-RS cells of MC- and NS-types.

PMID- 11318904
TI  - Assessing the risk of BRCA1-associated breast cancer using individual
      morphological criteria.

PMID- 11318905
TI  - Dermatofibroma (fibrous histiocytoma): an inflammatory or neoplastic disorder?

PMID- 11318906
TI  - Staining of malignant mesothelioma for the trefoil protein pS2.

PMID- 11318907
TI  - Inflammatory pseudotumour of the nasal cavity: an unusual lesion with regressing
      satellite nodules.

PMID- 11318909
TI  - Increased patient concern after false-positive mammograms: clinician
      documentation and subsequent ambulatory visits.
AB  - OBJECTIVE: To measure how often a breast-related concern was documented in
      medical records after screening mammography according to the mammogram result
      (normal, or true-negative vs false-positive) and to measure changes in health
      care utilization in the year after the mammogram. DESIGN: Cohort study. SETTING:
      Large health maintenance organization in New England. PATIENTS: Group of 496
      women with false-positive screening mammograms and a comparison group of 496
      women with normal screening mammograms, matched for location and year of
      mammogram. MEASUREMENTS AND MAIN RESULTS: 1) Documentation in clinicians' notes
      of patient concern about the breast and 2) ambulatory health care utilization,
      both breast-related and non-breast-related, in the year after the mammogram.
      Fifty (10%) of 496 women with false-positive mammograms had documentation of
      breast-related concern during the 12 months after the mammogram, compared to 1
      (0.2%) woman with a normal mammogram (P =.001). Documented concern increased with
      the intensity of recommended follow-up (P =.009). Subsequent ambulatory visits,
      not related to the screening mammogram, increased in the year after the mammogram
      among women with false-positive mammograms, both in terms of breast-related
      visits (incidence ratio, 3.07; 95% confidence interval [CI], 1.69 to 5.93) and
      non-breast-related visits (incidence ratio, 1.14; 95% CI, 1.03 to 1.25).
      CONCLUSIONS: Clinicians document concern about breast cancer in 10% of women who
      have false-positive mammograms, and subsequent use of health care services are
      increased among women with false-positive mammogram results.

PMID- 11318908
TI  - Improving depression outcomes in community primary care practice: a randomized
      trial of the quEST intervention. Quality Enhancement by Strategic Teaming.
AB  - OBJECTIVE: To determine whether redefining primary care team roles would improve
      outcomes for patients beginning a new treatment episode for major depression.
      DESIGN: Following stratification, 6 of 12 practices were randomly assigned to the
      intervention condition. Intervention effectiveness was evaluated by patient
      reports of 6-month change in 100-point depression symptom and functional status
      scales. SETTING: Twelve community primary care practices across the country
      employing no onsite mental health professional. PATIENTS: Using two-stage
      screening, practices enrolled 479 depressed adult patients (73.4% of those
      eligible); 90.2% completed six-month follow-up. INTERVENTION: Two primary care
      physicians, one nurse, and one administrative staff member in each intervention
      practice received brief training to improve the detection and management of major
      depression. MAIN RESULTS: In patients beginning a new treatment episode, the
      intervention improved depression symptoms by 8.2 points (95% confidence interval
      [CI], 0.2 to 16.1; P =.04). Within this group, the intervention improved
      depression symptoms by 16.2 points (95% CI, 4.5 to 27.9; P =.007), physical role
      functioning by 14.1 points (95% CI, 1.1 to 29.2; P =.07), and satisfaction with
      care (P =.02) for patients who reported antidepressant medication was an
      acceptable treatment at baseline. Patients already in treatment at enrollment did
      not benefit from the intervention. CONCLUSIONS: In practices without onsite
      mental health professionals, brief interventions training primary care teams to
      assume redefined roles can significantly improve depression outcomes in patients
      beginning a new treatment episode. Such interventions should target patients who
      report that antidepressant medication is an acceptable treatment for their
      condition. More research is needed to determine how primary care teams can best
      sustain these redefined roles over time.

PMID- 11318910
TI  - Measuring satisfaction with mammography results reporting.
AB  - OBJECTIVE: To assess factors associated with patient satisfaction with
      communication of mammography results and their understanding and ability to
      recall these results. DESIGN: Cross-sectional telephone survey. SETTING: Academic
      breast imaging center. PATIENTS: Two hundred ninety-eight patients who had either
      a screening or diagnostic mammogram. MEASUREMENTS AND MAIN RESULTS: Survey items
      assessed waiting time for results, anxiety about results, satisfaction with
      several components of results reporting, and patients' understanding of results
      and recommendations. Women undergoing screening exams were more likely to be
      dissatisfied with the way the results were communicated than those who underwent
      diagnostic exams and received immediate results (20% vs 11%, P =.05). For these
      screening patients, waiting for more than two weeks for notification of results,
      difficulty getting in touch with someone to answer questions, low ratings of how
      clearly results were explained, and considerable or extreme anxiety about the
      results were all independently associated with dissatisfaction with the way the
      results were reported, while age and actual exam result were not. CONCLUSIONS:
      Patients undergoing screening mammograms were more likely to be dissatisfied with
      the way the results were communicated than were those who underwent diagnostic
      mammograms. Interventions to reduce the wait time for results, reduce patients'
      anxiety, and improve the clarity with which the results and recommendations are
      given may help improve overall satisfaction with mammography result reporting.

PMID- 11318911
TI  - Primary care physicians' experience with disease management programs.
AB  - OBJECTIVE: To examine primary care physicians' perceptions of how disease
      management programs affect their practices, their relationships with their
      patients, and overall patient care. DESIGN: Cross-sectional mailed survey.
      SETTING: The 13 largest urban counties in California. PARTICIPANTS: General
      internists, general pediatricians, and family physicians. MEASUREMENTS AND MAIN
      RESULTS: Physicians' self-report of the effects of disease management programs on
      quality of patient care and their own practices. Respondents included 538 (76%)
      of 708 physicians: 183 (34%) internists, 199 (38%) family practitioners, and 156
      (29%) pediatricians. Disease management programs were available 285 to (53%)
      physicians; 178 had direct experience with the programs. Three quarters of the
      178 physicians believed that disease management programs increased the overall
      quality of patient care and the quality of care for the targeted disease. Eighty
      seven percent continued to provide primary care for their patients in these
      programs, and 70% reported participating in major patient care decisions. Ninety
      one percent reported that the programs had no effect on their income, decreased
      (38%) or had no effect (48%) on their workload, and increased (48%)) their
      practice satisfaction. CONCLUSIONS: Practicing primary care physicians have
      generally favorable perceptions of the effect of voluntary, primary care
      inclusive, disease management programs on their patients and on their own
      practice satisfaction.

PMID- 11318912
TI  - Comparison of the mineral content of tap water and bottled waters.
AB  - OBJECTIVES: Because of growing concern that constituents of drinking water may
      have adverse health effects, consumption of tap water in North America has
      decreased and consumption of bottled water has increased. Our objectives were to
      1) determine whether North American tap water contains clinically important
      levels of calcium (Ca2+), magnesium (Mg2+), and sodium (Na+) and 2) determine
      whether differences in mineral content of tap water and commercially available
      bottled waters are clinically important. DESIGN: We obtained mineral analysis
      reports from municipal water authorities of 21 major North American cities.
      Mineral content of tap water was compared with published data regarding
      commercially available bottled waters and with dietary reference intakes (DRIs).
      MEASUREMENTS AND MAIN RESULTS: Mineral levels varied among tap water sources in
      North America and among bottled waters. European bottled waters generally
      contained higher mineral levels than North American tap water sources and North
      American bottled waters. For half of the tap water sources we examined, adults
      may fulfill between 8% and 16% of their Ca2+ DRI and between 6% and 31% of their
      Mg2+ DRI by drinking 2 liters per day. One liter of most moderate mineralization
      European bottled waters contained between 20% and 58% of the Ca2+ DRI and between
      16% and 41% of the Mg2+ DRI in adults. High mineralization bottled waters often
      contained up to half of the maximum recommended daily intake of Na+. CONCLUSION:
      Drinking water sources available to North Americans may contain high levels of
      Ca2+, Mg2+, and Na+ and may provide clinically important portions of the
      recommended dietary intake of these minerals. Physicians should encourage
      patients to check the mineral content of their drinking water, whether tap or
      bottled, and choose water most appropriate for their needs.

PMID- 11318913
TI  - Improving physicians' HIV risk-assessment skills using announced and unannounced
      standardized patients.
AB  - OBJECTIVE: To evaluate feasibility and to validate a rating scale for two
      educational programs that use standardized patient-instructors (SPIs) in the
      office setting to improve physicians' HIV risk communication skills. DESIGN:
      Pilot randomized trial of announced and unannounced SPIs. PARTICIPANTS/SETTINGS:
      Twenty four primary care physicians in the Rochester, NY, area. MEASUREMENTS: The
      Rochester HIV Interview Rating Scale (RHIRS), HIV test ordering, physician
      satisfaction questionnaire. RESULTS: Physicians found the intervention useful,
      and predicted a positive effect on their future HIV-related communication. HIV
      test ordering and RHIRS scores increased similarly in both intervention groups.
      Announced SPI visits were more convenient and preferred by physicians. Cost for
      each SPI visit was $75. CONCLUSIONS: A brief office-based intervention using SPIs
      was feasible, well-accepted, convenient, and inexpensive. Announced SPIs were
      preferred to unannounced SPIs. Pilot results suggesting improvement in HIV
      related communication should be confirmed in a larger randomized trial.

PMID- 11318914
TI  - Physician incentives and disclosure of payment methods to patients.
AB  - OBJECTIVE: There is increasing public discussion of the value of disclosing how
      physicians are paid. However, little is known about patients' awareness of and
      interest in physician payment information or its potential impact on patients'
      evaluation of their care. DESIGN: Cross-sectional survey SETTING: Managed care
      and indemnity plans of a large, national health insurer. PARTICIPANTS: Telephone
      interviews were conducted with 2,086 adult patients in Atlanta, Ga; Baltimore,
      Md/Washington DC; and Orlando, Fla (response rate, 54%). MEASUREMENTS AND MAIN
      RESULTS: Patients were interviewed to assess perceptions of their physicians'
      payment method, preference for disclosure, and perceived effect of different
      financial incentives on quality of care. Non-managed fee-for-service patients
      (44%) were more likely to correctly identify how their physicians were paid than
      those with salaried (32%) or capitated (16%) physicians. Just over half (54%)
      wanted to be informed about their physicians' payment METHOD: Patients of
      capitated and salaried physicians were as likely to want disclosure as patients
      of fee-for-service physicians. College graduates were more likely to prefer
      disclosure than other patients. Many patients (76%) thought a bonus paid for
      ordering fewer than the average number of tests would adversely affect the
      quality of their care. About half of the patients (53%) thought a particular type
      of withhold would adversely affect the quality of their care. White patients,
      college graduates, and those who had higher incomes were more likely to think
      that these types of bonuses and withholds would have a negative impact on their
      care. Among patients who believed that these types of bonuses adversely affected
      care, those with non-managed fee-for-service insurance and college graduates were
      more willing to pay a higher deductible or co-payment in order to get tests that
      they thought were necessary. CONCLUSIONS: Most patients were unaware of how their
      physicians are paid, and only about half wanted to know. Most believed that
      bonuses or withholds designed to reduce the use of services would adversely
      affect the quality of their care. Lack of knowledge combined with strong
      attitudes about various financial incentives suggest that improved patient
      education could clarify patient understanding of the nature and rationale for
      different types of incentives. More public discussion of this important topic is
      warranted.

PMID- 11318915
TI  - Breast cancer outcomes among older women: HMO, fee-for-service, and delivery
      system comparisons.
AB  - OBJECTIVE: To analyze the relationship of health insurance status and delivery
      systems to breast cancer outcomes--stage at diagnosis, treatment selected,
      survival--focusing on comparisons among women aged 65 or more having Medicare
      alone, Medicare/Medicaid, or Medicare with group model HMO, non-group model HMO,
      or private fee-for-service (FFS) supplement. DESIGN: Retrospectively defined
      cohort from Sacramento, Calif, regional cancer registry. SETTING: Thirteen-county
      region in northern California with mature managed care market. PATIENTS: Female
      invasive breast cancer patients aged 65 or more (N = 1,146), diagnosed 1987-1993.
      MEASUREMENTS AND MAIN RESULTS: Health insurance was determined from hospital
      records. Outcomes were analyzed with multivariate regression models, controlling
      for age, ethnicity, time, and SES measures. Stage I diagnosis was more likely
      among group model HMO patients than among private FFS insured (odds ratio [OR],
      1.42; 95% confidence interval [CI], 0.84 to 2.40). Stage I tumors were
      significantly less likely for Medicaid patients (OR, 0.50; 95% CI, 0.31 to 0.82).
      Use of breast-conserving surgery plus radiation (BCS+) varied significantly by
      hospital type (including HMO-owned and various-sized community hospitals) and
      time. Survival of patients with private FFS, group-, and non-group model HMO
      insurance was not significantly different, but was for those with Medicaid or
      Medicare alone. CONCLUSIONS: This study sheds new light on the relationship of
      insurance to stage and survival among older breast cancer patients, highlighting
      the importance of distinguishing types of HMOs and types of FFS plans. These
      outcomes do not differ significantly between women with Medicare who are in HMOs
      and those with private FFS supplemental insurance. However, patients with
      Medicare/Medicaid or Medicare alone are at risk for poorer outcomes.

PMID- 11318916
TI  - The relation of household income to mammography utilization in a prepaid health
      care system.
AB  - Managed care organizations should be expected to provide equivalent access to
      preventive and screening services to all members. We studied mammography in 1,667
      women members of one HMO who had an overall utilization rate of 84.9%.
      Significant correlates of mammography utilization included age, estimated
      household income, and division of the managed care organization in which the
      member was enrolled. Each $10,000 increment of income increased mammography rates
      by 2.5 percentage points (95% confidence interval [CI], 1.4% to 3.6%),
      independent of age and division. Our findings suggest that coverage for
      mammography services is not sufficient to ensure equivalent use of screening
      across income groups.

PMID- 11318917
TI  - Money talks, patients walk?

PMID- 11318918
TI  - Breast cancer screening: can we talk?

PMID- 11318919
TI  - Communication breakdown in the outpatient referral process.

PMID- 11318920
TI  - Paid not to refer?

PMID- 11318921
TI  - Do gender and race affect decisions about pain management?
AB  - OBJECTIVE: To determine if patient gender and race affect decisions about pain
      management. DESIGN, SETTING, AND PARTICIPANTS: Experimental design using medical
      vignettes to evaluate treatment decisions. A convenience sample of 111 primary
      care physicians (61 men, 50 women) in the Northeast was asked to treat 3
      hypothetical patients with pain (kidney stone, back pain) or a control condition
      (sinusitis). Symptom presentation and severity were held constant, but patient
      gender and race were varied. MEASUREMENTS AND MAIN RESULTS: The maximum permitted
      doses of narcotic analgesics (hydrocodone) prescribed at initial and return
      visits were calculated by multiplying mg per pill x number of pills per day x
      number of days x number of refills. No overall differences with respect to
      patient gender or race were found in decisions to treat or in the maximum
      permitted doses. However, for renal colic, male physicians prescribed higher
      doses of hydrocodone to white patients versus black patients (426 mg vs 238 mg),
      while female physicians prescribed higher doses to blacks (335 mg vs 161 mg,
      F1,85 = 9.65, P =.003). This pattern was repeated for persistent kidney stone
      pain. For persistent back pain, male physicians prescribed higher doses of
      hydrocodone to males than to females (406 mg vs 201 mg), but female physicians
      prescribed higher doses to females (327 mg v. 163 mg, F1,28 = 5.50, P =.03).
      CONCLUSION: When treating pain, gender and racial differences were evident only
      when the role of physician gender was examined, suggesting that male and female
      physicians may react differently to gender and/or racial cues.

PMID- 11318922
TI  - Does physician gender affect satisfaction of men and women visiting the emergency
      department?
AB  - OBJECTIVE: To assess the association of physician gender with patient ratings of
      physician care. DESIGN: Interviewer-administered survey and follow-up interviews
      1 week after emergency department (ED) visit. SETTING: Public hospital ED.
      PATIENTS/PARTICIPANTS: English- and Spanish-speaking adults presenting for care
      of nonemergent problems; of 852 patients interviewed in the ED who were eligible
      for follow-up, 727 (85%) completed a second interview. MEASUREMENTS AND MAIN
      RESULTS: We conducted separate ordered logistic regressions for women and men to
      determine the unique association of physician gender with patient ratings of 5
      interpersonal aspects of care, their trust of the physician, and their overall
      ratings of the physician, controlling for patient age, health status, language
      and interpreter status, literacy level, and expected satisfaction. Female
      patients trusted female physicians more (P =.003) than male physicians and rated
      female physicians more positively on the amount of time spent (P =.01), on
      concern shown (P =.04), and overall (P =.03). Differences in ratings by female
      patients of male and female physicians in terms of friendliness (P =.13), respect
      shown (P =.74), and the extent to which the physician made them feel comfortable
      (P =.10) did not differ significantly. Male patients rated male and female
      physicians similarly on all dimensions of care (overall, P =.74; friendliness, P
      =.75; time spent, P =.30; concern shown, P =.62; making them feel comfortable, P
      =.75; respect shown, P =.13; trust, P =.92). CONCLUSIONS: Having a female
      physician was positively associated with women's satisfaction, but physician
      gender was not associated with men's satisfaction. Further studies are needed to
      identify reasons for physician gender differences in interpersonal care delivered
      to women.

PMID- 11318923
TI  - Do race and gender influence the use of invasive procedures?
AB  - OBJECTIVE: To assess the influence of race and gender influence on the use of
      invasive procedures in patients with acute myocardial infarction (AMI) in
      community hospitals. DESIGN: Prospective, observational. SETTING: Five mid
      Michigan community hospitals. PATIENTS: All patients (838) identified with AMI
      between January 1994 and April 1995 in 1 of these hospitals. MEASUREMENTS AND
      MAIN RESULTS: After adjusting for age, hospital of admission, insurance type,
      severity of AMI, and comorbidity, using white men as the reference group, the
      rate of being offered cardiac catheterization (CC) was 0.88 (95% confidence
      interval [95% CI], 0.60 to 1.29) for white women; 0.79 (95% CI, 0.41 to 1.50) for
      black men; and 1.14 (95% CI, 0.53 to 2.45)for black women. Among patients who
      underwent CC, after also adjusting for coronary artery anatomy, the rate of being
      offered angioplasty, using white men as the reference group, was 1.22 (95% CI,
      0.75 to 1.98) for white women; 0.61 (5% CI, 0.29 to 1.28, P =.192) for black men;
      and 0.40 (95% CI, 0.14 to 1.13) for black women The adjusted rate of being
      offered bypass surgery was 0.47 (95% CI, 0.24 to 0.89) for white women; 0.36 (95%
      CI, 0.12 to 1.06) for black men; and 0.37 (95% CI, 0.11 to 1.28)for black women.
      CONCLUSIONS: Our study shows that white women are less likely than white men to
      be offered bypass surgery after AMI. Although black men and women with AMI are
      less likely than white men to be offered percutaneous transluminal coronary
      angioplasty or coronary artery bypass grafting in both unadjusted and adjusted
      analyses, these findings did not reach statistical significance. Our study is
      limited in power due to the small number of blacks in the sample.

PMID- 11318924
TI  - Mobility difficulties are not only a problem of old age.
AB  - BACKGROUND: Lower extremity mobility difficulties often result from common
      medical conditions and can disrupt both physical and emotional well-being.
      OBJECTIVES: To assess the national prevalence of mobility difficulties among
      noninstitutionalized adults and to examine associations with demographic
      characteristics and other physical and mental health problems. DESIGN: Cross
      sectional survey using the 1994-1995 National Health Interview Survey-Disability
      Supplement (NHIS-D). We constructed measures of minor, moderate, and major lower
      extremity mobility difficulties using questions about ability to walk, climb
      stairs, and stand, and use of mobility aids (e.g., canes, wheelchairs). Age and
      gender adjustment used direct standardization methods in Software for the
      Statistical Analysis of Correlated Data (SUDAAN). PARTICIPANTS:
      Noninstitutionalized, civilian U.S. residents aged 18 years and older. National
      Health Interview Survey sampling weights with SUDAAN provided nationally
      representative population estimates. RESULTS: An estimated 19 million people
      (10.1%) reported some mobility difficulty. The mean age of those with minor,
      moderate, or major difficulty ranged from 59 to 67 years. Of those reporting
      major difficulties, 32% said their problems began at aged 50 years or younger.
      Adjusted problem rates were higher among women (11.8%) than men (8.8%), and
      higher among African American (15.0%) than whites (10.0%). Persons with mobility
      difficulties were more likely to be poorly educated, living alone, impoverished,
      obese, and having problems conducting daily activities. Among persons with major
      mobility difficulties, 30.6% reported being frequently depressed or anxious,
      compared to 3.8% for persons without mobility difficulties. CONCLUSIONS: Reports
      of mobility difficulties are common, including among middle-aged adults.
      Associations with poor performance of daily activities, depression, anxiety, and
      poverty highlight the need for comprehensive care for persons with mobility
      problems.

PMID- 11318925
TI  - Introduction of evidence-based medicine into an ambulatory clinical clerkship.
AB  - Evidence-based medicine (EBM) has emerged has a critical clinical competency in
      the 21st century. Medical schools usually introduce students to critical
      appraisal in the preclinical years, but there have been few evaluated
      interventions in teaching EBM in the clinical years. We describe a strategy to
      encourage students to practice EBM during a required ambulatory medicine
      clerkship. During this clerkship, our students are required to submit an EBM
      report, which is prompted by an individual case, and structured with a 5-step
      approach. One small-group session is devoted to modeling this approach with a
      case of chest pain. Using a checklist to grade 216 consecutive EBM reports, we
      found that students were quite successful with the exercise, achieving on average
      89.6% of possible checklist points. Students who followed the structure of the
      exercise closely were more likely to extend their discussions beyond that
      required and to suggest potential further areas of investigation or design.

PMID- 11318926
TI  - The future of capitation: the physician role in managing change in practice.
AB  - Capitation-based reimbursement significantly influences the practice of medicine.
      As physicians, we need to assure that payment models do not jeopardize the care
      we provide when we accept higher levels of personal financial risk. In this
      paper, we review the literature relevant to capitation, consider the interaction
      of financial incentives with physician and medical risk, and conclude that
      primary care physicians need to work to assure that capitated systems incorporate
      checks and balances which protect both patients and providers. We offer the
      following proposals for individuals and groups considering capitated contracts:
      (1) reimbursement for primary care physicians should recognize both individual
      patient encounters and the administrative work of patient care management; (2)
      reimbursement for subspecialists should recognize both access to subspecialty
      knowledge and expertise as well as patient care encounters, but in some
      situations, subspecialists may provide the majority of care to individual
      patients and will be reimbursed as primary care providers; (3) groups of
      physicians should accept financial risk for patient care only if they have the
      tools and resources to manage the care; (4) physicians sharing risk for patient
      care should meet regularly to discuss care and resource management; and (5)
      physicians must disclose the financial relationships they have with health plans
      and medical care organizations, and engage patients and communities in
      discussions about resource allocation. As a payment model, capitation offers
      opportunities for primary care physicians to influence the future of health care
      by improving the management of resources at a local level.

PMID- 11318927
TI  - Preventive care of older urban American Indians and Alaska natives in primary
      care.
AB  - Little is known about prevention among elderly or urban American Indian/Alaska
      Native (AI/AN) populations. We reviewed the medical records of 550 older urban
      AI/AN primary care patients to evaluate how frequently preventive measures were
      received. Adherence to guidelines was examined by a culturally appropriate (> or
      =50 years) and standard age threshold (> or =65 years), and by performance of
      preventive measures at any time ("ever") and in the past year. Lifetime
      performance was inadequate for the many measures, including mammograms (56%),
      fecal occult blood testing (37%), audiometry (33%), visual acuity testing (50%),
      smoking cessation counseling (50%), and pneumococcal (22%) and influenza (49%)
      vaccinations. Performance of the measures was less frequent in the prior year,
      but did not differ by age threshold. Predictors of adherence included female
      gender, having insurance, and having more health problems and medications.
      Nonadherence infrequently resulted from patients' failure to comply with
      recommendations. We conclude that use of most preventive services among elderly
      urban AI/ANs is suboptimal and should be improved.

PMID- 11318928
TI  - The effect of obesity on medical students' approach to patients with abdominal
      pain.
AB  - Because widely held stereotypes characterize obese people as less intelligent,
      unhappy, lacking in self control and more prone to psychological problems, we
      tested whether obese appearance alone would affect medical students' decisions
      about the diagnosis and management of simulated patients. We videotaped 4 patient
      simulators presenting each of 4 cases in 2 states: normal and obese (by using
      padding and bulky clothing). Seventy-two clinical students at 2 medical schools
      viewed the cases and answered questions about diagnostic tests and management. We
      found the expected biases toward patients when in their obese form as well as
      pessimism about patient compliance and success of therapy, but there were no
      significant differences in tests or treatments ordered except where appropriate
      for an obese patient (e.g., weight reduction diet). Thus, the appearance of
      obesity alone biased the students' impressions of the patients, but did not
      affect diagnostic test ordering.

PMID- 11318929
TI  - Somatic symptom reporting in women and men.
AB  - Women report more intense, more numerous, and more frequent bodily symptoms than
      men. This difference appears in samples of medical patients and in community
      samples, whether or not gynecologic and reproductive symptoms are excluded, and
      whether all bodily symptoms or only those which are medically unexplained are
      examined. More limited, but suggestive, literature on experimental pain, symptom
      reporting in childhood, and pain thresholds in animals are compatible with these
      findings in adults. A number of contributory factors have been implicated,
      supported by varying degrees of evidence. These include innate differences in
      somatic and visceral perception; differences in symptom labeling, description,
      and reporting; the socialization process, which leads to differences in the
      readiness to acknowledge and disclose discomfort; a sex differential in the
      incidence of abuse and violence; sex differences in the prevalence of anxiety and
      depressive disorders; and gender bias in research and in clinical practice.
      General internists need to keep these factors in mind in obtaining the clinical
      history, understanding the meaning and significance that symptoms hold for each
      patient, and providing symptom relief.

PMID- 11318930
TI  - Disparities in health and health care: moving from describing the problem to a
      call for action.

PMID- 11318931
TI  - Capitation's uncertain future.

PMID- 11318932
TI  - The moth and the aspen tree: sodium in early postnatal development.
AB  - Over the past 25 years, our perception of the neonatal kidney has changed
      markedly from its being a "limited" organ compared with that of the adult to
      being extraordinarily well adapted in its role in maintaining homeostasis and
      making possible the rapid somatic growth necessary during this critical period of
      life. The present review focuses on the physiologic adaptations by the neonatal
      kidney in the maintenance of a positive sodium balance, which is necessary for
      normal growth not only in mammals but also in moths. There is a fine interplay
      between the developing brain, heart, thyroid, adrenals, and sympathetic nervous
      system, all converging on the kidney to conserve sodium, which is limited in the
      diet. The renin-angiotensin system plays a central role in this response and is
      balanced by developmental changes in the renal response to atrial natriuretic
      peptide, all of which contribute to sodium conservation. Over the next 25 years,
      advances in molecular genetics will doubtless elucidate many more facets of the
      mechanisms underlying neonatal sodium homeostasis. This will be particularly
      important as the survival of ever smaller preterm infants improves steadily.

PMID- 11318934
TI  - In vitro studies on the roles of transforming growth factor-beta 1 in rat
      metanephric development.
AB  - BACKGROUND: The development of the permanent kidney (metanephros) involves the
      interplay between both positive and negative regulatory molecules. Transforming
      growth factor-beta1 (TGF-beta 1) has previously been shown to negatively regulate
      ureteric duct growth. However, its potential role in nephron development and
      glomerulogenesis has been largely ignored. METHODS: In situ hybridization and
      reverse transcription-polymerase chain reaction were employed to examine the
      temporal and spatial localization of TGF-beta 1 mRNA and a TGF-beta type I
      receptor (activin-like receptor kinase-5; ALK-5) mRNA in developing rat
      metanephroi. The addition of exogenous TGF-beta 1 to rat metanephric organ
      culture at different time points was used to examine the role of TGF-beta 1 in
      ureteric duct growth and nephron development. RESULTS: TGF-beta 1 mRNA did not
      colocalize with ALK-5 mRNA. Instead, TGF-beta1 mRNA colocalized with the TGF-beta
      type II receptor mRNA. The addition of recombinant human TGF-beta 1 to rat
      metanephric organ culture at the beginning of the culture period inhibited total
      metanephric growth and the growth of the ureteric tree, resulting in a decrease
      in nephron number. Similarly, the addition of TGF-beta 1 to metanephroi after 48
      hours of culture inhibited ureteric duct growth, decreasing nephron number. The
      addition of TGF-beta 1 at days 0 or 2 of culture promoted hypertrophy of the
      renal capsule. CONCLUSIONS: These findings confirm that TGF-beta 1 inhibits
      ureteric duct growth and thereby nephron endowment in developing rat metanephroi
      in vitro. However, TGF-beta 1 does not appear to play a significant role in
      nephron development per se once the epithelial vesicle has formed.

PMID- 11318933
TI  - Role of immunocompetent cells in nonimmune renal diseases.
AB  - Renal infiltration with macrophages and monocytes is a well-recognized feature of
      not only immune, but also nonimmune kidney disease. This review focuses on the
      investigations that have shown accumulation of immunocompetent cells in
      experimental models of acute and chronic ischemia, protein overload,
      hypercholesterolemia, renal ablation, obstructive uropathy, polycystic kidney
      disease, diabetes, aging, murine hypertension, and nephrotoxicity. We examine the
      mechanisms of infiltration of immunocompetent cells and their participation in
      the self-perpetuating cycle of activation of the angiotensin system, generation
      of reactive oxygen species, and further recruitment of monocytes and lymphocytes.
      We also discuss the possibility of antigen-dependent and antigen-independent
      mechanisms of immune cell activation in these animal models. Finally, we review
      the recent studies in which suppression of cellular immunity with mycophenolate
      mofetil has proven beneficial in attenuating or preventing the progression of
      renal functional and histologic damage in experimental conditions of nonimmune
      nature.

PMID- 11318935
TI  - Progression of autosomal-dominant polycystic kidney disease in children.
AB  - BACKGROUND: Although many case reports describe manifestations of autosomal
      dominant polycystic kidney disease (ADPKD) in children, no longitudinal studies
      have examined the natural progression or risk factors for more rapid progression
      in a large number of children from ADPKD families. METHODS: Since 1985, we have
      studied 312 children from 131 families with a history, a physical examination,
      blood and urine chemistries, an abdominal ultrasonography, and gene linkage
      analysis. One hundred fifteen of 185 affected children were studied multiple
      times for up to 15 years. Renal volumes were determined by ultrasound imaging.
      Graphs of mean renal volumes according to age were compared between affected and
      unaffected children, ADPKD children with and without early severe disease, and
      children with and without high blood pressure. RESULTS: Affected children had
      faster renal growth than unaffected children. ADPKD children with severe renal
      enlargement at a young age continued to experience faster renal growth than those
      with mild enlargement or normal kidney size for their age, and affected children
      with high blood pressure had faster renal growth than those with lower blood
      pressure. Glomerular filtration rate did not decrease in any children except for
      two with unusually severe early onset disease. CONCLUSIONS: The progression of
      ADPKD clearly occurs in childhood and manifests as an increase in cyst number and
      renal size. This study identifies children at risk for rapid renal enlargement
      who may benefit the most from future therapeutic interventions.

PMID- 11318937
TI  - Segregation of hematuria in thin basement membrane disease with haplotypes at the
      loci for Alport syndrome.
AB  - BACKGROUND: Inherited hematuria is common and is usually attributed to thin
      basement membrane disease (TBMD). The aim of this study was to determine how
      often hematuria in families with TBMD segregated with haplotypes at the
      chromosomal loci for autosomal recessive and X-linked Alport syndrome
      (COL4A3/COL4A4 and COL4A5, respectively). METHODS: The families of 22 individuals
      with TBMD on renal biopsy and with urinary glomerular red blood cell (RBC) counts
      of more than 50,000/mL were studied using phase-contrast microscopy of the urine
      and DNA microsatellite markers. Eighteen families had at least two members with
      hematuria. RESULTS: Hematuria segregated with or was consistent with segregation
      at the COL4A3/COL4A4 locus in eight (36%) families (P < 0.05 in 5 of these) and
      at the COL4A5 locus in four (18%) families (P < 0.05 in 2). The lack of
      segregation in the other 10 (45%) families may have occurred because of
      incomplete penetrance of the hematuria, de novo mutations, coincidental hematuria
      in other family members, or the presence of a novel gene locus. In four different
      families, three of which had hematuria that segregated with the COL4A3/COL4A4
      locus, four family members with the hematuria haplotype had spouses with
      coincidental hematuria (4 of 29, 14%). However, none of their four offspring who
      had also inherited the hematuria haplotype had the clinical features of autosomal
      recessive Alport syndrome. CONCLUSIONS: Hematuria in families with TBMD commonly
      segregates with the COL4A3/COL4A4 locus and thus results from mutations in the
      same genes as autosomal recessive Alport syndrome. Sometimes TBMD may be confused
      with the carrier state for X-linked Alport syndrome. However, nearly half of the
      families in this study had hematuria that did not segregate with the loci for
      either autosomal recessive or X-linked Alport syndrome.

PMID- 11318936
TI  - Effect of prenatal dexamethasone on rat renal development.
AB  - BACKGROUND: Prenatal insults can program the developing fetus to develop diseases
      that manifest in later life. Dexamethasone is often administered to the
      developing fetus to accelerate pulmonary development. The purpose of the present
      study was to determine whether prenatal dexamethasone adversely affects renal
      development and predisposes rats to develop renal disease and hypertension in
      later life. METHODS: Pregnant rats were given either vehicle or two daily
      intraperitoneal injections of dexamethasone (0.2 mg/kg body weight) on
      gestational days: 11 and 12, 13 and 14, 15 and 16, 17 and 18, 19 and 20, or 20
      and 21. Tail cuff blood pressure, glomerular number, and inulin clearance were
      measured in control and prenatal dexamethasone-treated rats when the rats were 60
      to 90 days of age. RESULTS: Prenatal dexamethasone did not affect the length of
      gestation, the number of animals per litter, or the total body weight or kidney
      weight measured at one day of age. Offspring of rats administered dexamethasone
      on days 15 and 16 gestation had a 30% reduction in glomerular number compared
      with control at 60 to 70 days of age (24,236 +/- 441 vs. 30,453 +/- 579, P <
      0.01). Rats receiving prenatal dexamethasone on days 17 and 18 had an approximate
      20% reduction in glomeruli compared with control (P < 0.01). Offspring of rats
      receiving dexamethasone on days 15 and 16 gestation had systolic blood pressures
      at 60 to 90 days of age that were higher than any other group (P < 0.05). The
      glomerular filtration rate was comparable in all of the groups. CONCLUSIONS: This
      study shows that two daily doses of prenatal dexamethasone (0.2 mg/kg body
      weight) in rats do not produce intrauterine growth retardation. Adult offspring
      of rats that received prenatal dexamethasone during specific times of gestation
      have a reduced number of nephrons and hypertension.

PMID- 11318938
TI  - Autosomal-dominant periodic fever with AA amyloidosis: Novel mutation in tumor
      necrosis factor receptor 1 gene Rapid Communication.
AB  - BACKGROUND: The recent identification of genes responsible for syndromes of
      periodic fever with amyloidosis has opened the way to a molecular diagnosis of
      hereditary AA amyloidosis. METHODS: A Belgian woman presented for genetic
      counseling. Three first-degree relatives had a diagnosis of renal amyloidosis
      with a history of recurrent fever and inflammatory episodes. Medical records and
      pathological specimens were obtained from all physicians who had been in charge
      of her three relatives. Immunohistochemical staining was performed on paraffin
      embedded material. A mutation search was performed in the MEFV (Mediterranean
      fever) and tumor necrosis factor receptor 1 (TNFR1 or TNFRSF1A) genes causing
      familial Mediterranean fever (FMF) and tumor necrosis factor receptor-associated
      periodic syndrome (TRAPS), respectively. RESULTS: The family history was
      consistent with autosomal-dominant transmission of periodic fever with
      arthralgias, abdominal pain, and eventual AA amyloidosis involving the kidneys,
      digestive tract, and thyroid. Recurrent amyloidosis in kidney graft was
      demonstrated in one patient and was suspected in the other. A novel heterozygous
      mutation (C55S) in TNFRSF1A was identified in the affected patient available for
      genetic testing but not in the asymptomatic woman requiring counseling. No
      mutation was detected in MEFV. CONCLUSIONS: We report a novel mutation (C55S) in
      TNFRSF1A, resulting in autosomal-dominant periodic fever and AA amyloidosis. This
      condition, known as TRAPS, should be added to the differential diagnosis of
      hereditary renal amyloidosis, with obvious implications for management and
      genetic counseling.

PMID- 11318939
TI  - D1-like dopamine receptor activation and natriuresis by nitrocatechol COMT
      inhibitors.
AB  - BACKGROUND: In recent years, several nitrocatechol derivatives (tolcapone,
      entacapone, and nitecapone) have been developed and found to be highly selective
      and potent inhibitors of catechol-O-methyltransferase (COMT). More recently,
      natriuretic properties were described for two of these compounds (entacapone and
      nitecapone), although this was not accompanied by enhanced urinary excretion of
      dopamine. We hypothesized that nitrocatechol derivatives stimulate D1-like
      dopamine receptors. METHODS: Adult male Wistar rats were treated with a
      nitrocatechol COMT inhibitor (entacapone, tolcapone, or nitecapone, 30 mg/kg,
      orally), and the urinary excretion of dopamine and sodium was quantitated. The
      interaction of nitrocatechol derivatives with D1-like receptors was evaluated by
      their ability to displace [3H]-Sch23390 binding from membranes of rat renal
      cortex and cAMP production in opossum kidney (OK) cells. RESULTS: Urinary
      excretion of sodium (micromol/h) was markedly increased by all three
      nitrocatechol derivatives: vehicle, 55.0 +/- 5.6; entacapone, 98.4 +/- 9.3;
      tolcapone, 97.5 +/- 9.3; and nitecapone, 120.5 +/- 12.6. Pretreatment with the
      selective D1 antagonist Sch 23390 (60 microg/kg) completely prevented their
      natriuretic effects. Nitecapone and tolcapone were equipotent (IC50s of 48 and 42
      micromol/L) and more potent than entacapone and dopamine (IC50s of 107 and 279
      micromol/L) in displacing [3H]-Sch23390 binding. In OK cells, all three
      nitrocatechol derivatives significantly increased cAMP accumulation and reduced
      Na(+)/H(+) exchange and Na(+),K(+)-ATPase activities, this being prevented by a
      blockade of D1-like receptors. CONCLUSION: Stimulation of D1-like dopamine
      receptors and inhibition of Na(+)/H(+) exchange and Na(+),K(+)-ATPase activities
      by nitrocatechol COMT inhibitors may contribute to natriuresis produced by these
      compounds.

PMID- 11318940
TI  - High glucose inhibits renal proximal tubule cell proliferation and involves PKC,
      oxidative stress, and TGF-beta 1.
AB  - BACKGROUND: The alteration of renal cell growth is one of the early abnormalities
      in the diabetic nephropathy. However, the effects of high glucose and its action
      mechanism in renal proximal tubule cell (PTC) proliferation have not been
      elucidated. METHODS: The effects of 25 mmol/L glucose on cell proliferation,
      thymidine, and leucine incorporation, cell cycle, and lipid peroxide formation
      were examined in the primary cultured renal PTCs. RESULTS: Glucose 25 mmol/L
      inhibited [3H]-thymidine incorporation and decreased cell growth. However, it
      increased [3H]-leucine incorporation and protein content. Furthermore, 25 mmol/L
      glucose increased lipid peroxide formation. These effects of glucose were blocked
      by antioxidants, vitamin E, N-acetylcystein, or taurine. Staurosporine and H-7
      totally blocked 25 mmol/L glucose-induced lipid peroxide formation and had an
      inhibitory effect on [3H]-thymidine incorporation. Indeed, 25 mmol/L glucose
      increased the translocation of protein kinase C (PKC) from cytosolic fraction to
      membrane fraction. In addition, high glucose increased the secretion of
      transforming growth factor-beta1 (TGF-beta 1) via the PKC-oxidative stress
      pathway, and TGF-beta 1 inhibited [3H]-thymidine incorporation in a dose
      dependent manner. CONCLUSIONS: High glucose inhibits renal PTC proliferation via
      PKC, oxidative stress, and the TGF-beta 1 signaling pathway.

PMID- 11318941
TI  - Glucocorticoids stimulate p21(CIP1) in mesangial cells and in anti-GBM
      glomerulonephritis.
AB  - BACKGROUND: Glucocorticoids are widely used for the treatment of
      glomerulonephritis, but the mechanism of cell cycle inhibition by glucocorticoids
      is poorly understood at a molecular level. METHODS: The effects of dexamethasone
      on cell cycle progression were examined in rat mesangial cells. To investigate
      the mechanisms of cell cycle inhibition by dexamethasone, we transfected the -2.3
      kb p21(CIP1) promoter-CAT construct to mesangial cells using an electroporation
      METHOD: We also examined whether glucocorticoids stimulate the expression of
      p21(CIP1) and inhibit cell proliferation in glomeruli of anti-glomerular basement
      membrane (GBM) glomerulonephritis in rats. RESULTS: Dexamethasone inhibited 3H
      thymidine uptake and the percentages of S and G2/M phases in rat mesangial cells.
      Dexamethasone stimulated CAT activity of the p21(CIP1) promoter 4.5-fold.
      Deletion analysis of the p21(CIP1) promoter revealed that the glucocorticoid
      responsive region (GRE) is present between -1.4 and -1.1 kb upstream of the
      transcription initiation site. Dexamethasone inducibility of p21(CIP1) promoter
      activity requires the presence of the C/EBP alpha DNA binding site in the GRE of
      the p21(CIP1) promoter and C/EBP alpha protein. Intravenous injection of anti-GBM
      antibody caused mesangial proliferation, crescent formation, and proteinuria in
      rats. Ten days of administration of prednisolone (1 mg/kg/day) reduced
      proteinuria and inhibited mesangial cell proliferation and crescent formation.
      The glomerular-sieving method revealed that prednisolone increased p21(CIP1)
      expression in glomeruli. CONCLUSION: These data suggest that the cell cycle
      arrest of mesangial cells is mediated by a functional link between the
      glucocorticoid receptor and the transcriptional control of p21(CIP1) not only in
      vitro but also in vivo. Our observations provide new insights into the molecular
      mechanisms of glucocorticoid action in glomerulonephritis.

PMID- 11318942
TI  - Up-regulation of a fibroblast growth factor binding protein in children with
      renal diseases.
AB  - BACKGROUND: Basic fibroblast growth factor (bFGF) is an angiogenic growth factor
      that is involved in renal growth and the pathogenesis of renal diseases. We have
      detected high levels of bFGF accumulated in the kidney of HIV-transgenic mice and
      in children with HIV-associated renal diseases and the hemolytic uremic syndrome
      (HUS). However, the mechanism modulating the activity of bFGF under these
      circumstances is poorly understood. We carried out experiments to determine
      whether a secreted binding protein (FGF-BP) that modulates the activity of bFGF
      during the process of tumor growth was expressed in pediatric kidneys and to
      define whether the expression of FGF-BP was altered in pediatric renal diseases
      associated with high levels of bFGF. METHODS: Immunohistochemistry and in situ
      hybridization studies were done in 41 renal sections from children with HIV
      nephropathies, HUS, other pediatric renal diseases, controls, and fetal kidneys.
      Western blots and reverse transcriptase-polymerase chain reaction studies were
      done in selected urine samples and cultured renal cells. Recombinant FGF-BP was
      produced to study the mitogenic activity of FGF-BP in cultured human renal
      proximal tubular epithelial cells (RPTEcs). RESULTS: The expression of FGF-BP was
      up-regulated predominately in renal tubular epithelial cells in children with
      renal tubular injury, HIV-associated nephropathy (HIVAN), and HUS, and FGF-BP was
      secreted in the urine of these patients. FGF-BP was also abundantly expressed in
      developing fetal renal tubules. Recombinant FGF-BP enhanced the mitogenic effects
      of bFGF in cultured human RPTEcs. CONCLUSIONS: The localization of FGF-BP in
      renal tubular epithelial cells could provide a mechanism by which the activity of
      bFGF is modulated in developing and regenerating renal tubules of children.

PMID- 11318943
TI  - Neutrophil priming and apoptosis in anti-neutrophil cytoplasmic autoantibody
      associated vasculitis.
AB  - BACKGROUND: Interactions between anti-neutrophil cytoplasmic autoantibody (ANCA)
      and primed neutrophils (PMNs) may be central to the pathogenesis of primary small
      vessel vasculitis. PMNs from patients are primed, expressing proteinase 3 (PR3)
      on the cell surface, which permits interaction with ANCA. In vitro ANCA activates
      primed PMN to degranulate and generate a respiratory burst. Resultant reactive
      oxygen species are important in triggering apoptosis, but the fate of PMN in ANCA
      associated vasculitis is unknown. Failure to remove apoptotic PMN in a
      nonphlogistic manner may sustain the inflammatory response. METHODS: PMNs from
      patients or controls were isolated, and the basal production of superoxide was
      measured by the superoxide dismutase-inhibitable reduction of ferricytochrome C.
      ANCA antigen expression on apoptotic PMN was assessed at 0, 12, and 18 hours by
      flow cytometry using dual staining with FITC-conjugated annexin V and PE
      conjugated anti-murine IgG against monoclonal ANCA. Apoptosis was also assessed
      by morphology. In further studies, apoptotic PMNs were opsonized with monoclonal
      anti-myeloperoxidase (MPO) or anti-proteinase-3 (PR3) or irrelevant isotype
      matched IgG (N IgG) and phagocytosis by macrophages was measured using
      interaction assays. Cytokines interleukin-8 (IL-8) and interleukin-1 were
      measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Proteinase-3
      expression (active 63.04 +/- 5.6% of total number of cells, remission 51.47 +/-
      7.9% of total number of cells, control 17.7 +/- 4.7% of total number of cells, P
      < 0.05) and basal superoxide production (active 6.9 +/- 0.8 nmol/L x 10(6) cells,
      remission 5.15 +/- 0.4 nmol/L/10(6) cells, control 3.63 +/- 0.3 nmol/L/10(6)
      cells, P < 0.001) were significantly greater with freshly isolated PMN from
      patients than controls. PR3 expression and superoxide generation were positively
      correlated. PMN from patients with active disease became apoptotic at a greater
      rate than those of controls (at 18 hours, patients 72.3 +/- 3.9% apoptosis,
      controls 53.2 +/- 2.7% apoptosis, P < 0.05). PR3 and MPO expression were
      significantly greater on PMN isolated from patients at 12 and 18 hours.
      Opsonization of apoptotic PMN with ANCA significantly enhanced recognition and
      phagocytosis by scavenger macrophages (anti-MPO 88.95 +/- 6.27, anti-PR3 93.98 +/
      4.90, N IgG 44.89 +/- 3.44, P < 0.01) with increased secretion of IL-1 (anti-PR3
      34.73 +/- 6.8 pg/mL, anti-MPO 42.01 +/- 12.3 pg/mL, N IgG 8.04 +/- 6.3 pg/mL, P <
      0.05) and IL-8 (anti-PR3 8.97 +/- 0.93 ng/mL, anti-MPO 8.45 +/- 1.46 ng/mL, N IgG
      0.96 +/- 0.15 ng/mL, P < 0.01). CONCLUSION: In vivo circulating PMNs are primed
      as assessed by PR3 expression and basal superoxide production, thereby enhancing
      their inflammatory potential. These PMNs undergo apoptosis more readily, at which
      times they express PR3 and MPO on their surface. These antigens may then provide
      targets for ANCA. Opsonization of apoptotic PMN will enhance clearance by
      macrophages but will also trigger the release of pro-inflammatory cytokines that
      may contribute to chronic inflammation.

PMID- 11318944
TI  - Regulation of renal proximal tubular epithelial cell hyaluronan generation:
      implications for diabetic nephropathy.
AB  - BACKGROUND: Proximal tubular cells (PTCs) contribute to pathological changes in
      the renal interstitium by the generation of cytokines and alterations in the
      composition of the extracellular matrix. Hyaluronan (HA) is a ubiquitous
      connective tissue polysaccharide that regulates cell function and tissue
      remodeling. In the current study, we investigated the regulation of HA generation
      by PTCs. METHODS: Primary cultures of human PTCs were grown to confluence and
      stimulated under serum-free conditions with either interleukin-1 (IL-1) or 25
      mmol/L D-glucose. Alterations in HA generation were detected by enzyme-linked
      immunosorbent assay, and alterations in HA synthase gene expression were examined
      by reverse transcription-polymerase chain reaction. Subsequently, the mechanisms
      of IL-1 beta and glucose-induced alterations in HA were examined utilizing HK-2
      cells. RESULTS: Stimulation of human PTCs (HPTCs) with either IL-1 beta or 25
      mmol/L D-glucose led to a significant increase in the HA concentration in the
      culture supernatant. In contrast, stimulation of HPTCs with transforming growth
      factor-beta1, basic fibroblast growth factor, or platelet-derived growth factor
      AB did not stimulate HA production. The addition of IL-1 beta or 25 mmol/L D
      glucose also increased HA generation in HK-2 cells and was associated with the
      induction of HAS2 mRNA. HAS3 mRNA was constitutively expressed and was not
      influenced by the addition of either stimulus. HAS1 mRNA expression was not
      detected in either unstimulated or stimulated cells. Inhibition of gene
      transcription or protein synthesis abolished HA production in response to either
      IL-1 beta or glucose. Inhibition of nuclear factor-kappa B (NF-kappa B)
      activation either by sulindac or by the proteosome inhibitor (PSI) abrogated both
      IL-1 beta and glucose-mediated alteration in HA synthesis. CONCLUSION: This study
      demonstrates, to our knowledge for the first time, that increased HA synthesis in
      response to either IL-1 beta or elevated 25 mmol/L D-glucose is associated with
      NF-kappa B-activated transcription of HAS2.

PMID- 11318945
TI  - Cholesterol ester accumulation: an immediate consequence of acute in vivo
      ischemic renal injury.
AB  - BACKGROUND: Cholesterol is a major constituent of plasma membranes, and recent
      evidence indicates that it is up-regulated during the maintenance phase of acute
      renal failure (ARF). However, cholesterol's fate and that of the cholesterol
      ester (CE) cycle [shuttling between free cholesterol (FC) and CEs] during the
      induction phase of ARF have not been well defined. The present studies sought to
      provide initial insights into these issues. METHODS: FC and CE were measured in
      mouse renal cortex after in vivo ischemia (15 and 45 minutes)/reperfusion (0 to
      120 minutes) and glycerol-induced myoglobinuria (1 to 2 hours). FC/CE were also
      measured in (1) cultured human proximal tubule (HK-2) cells three hours after ATP
      depletion and in (2) isolated mouse proximal tubule segments (PTSs) subjected to
      plasma membrane damage (with cholesterol oxidase, sphingomyelinase, phospholipase
      A2, or cytoskeletal disruption with cytochalasin B). The impact of cholesterol
      synthesis inhibition (with mevastatin) and FC traffic blockade (with
      progesterone) on injury-evoked FC/CE changes was also assessed. RESULTS: In vivo
      ischemia caused approximately threefold to fourfold CE elevations, but not FC
      elevations, that persisted for at least two hours of reperfusion. Conversely,
      myoglobinuria had no effect. Isolated CE increments were observed in ATP-depleted
      HK-2 cells. Neither mevastatin nor progesterone blocked this CE accumulation.
      Plasma membrane injury induced with sphingomyelinase or cholesterol oxidase, but
      not with phospholipase A(2) or cytochalasin B, increased tubule CE content. High
      CE levels, induced with cholesterol oxidase, partially blocked hypoxic PTS
      attack. CONCLUSIONS: In vivo ischemia/reperfusion acutely increases renal
      cortical CE, but not FC, content, indicating perturbed CE/FC cycling. The
      available data suggest that this could stem from specific types of plasma
      membrane damage, which then increase FC flux via aberrant pathways to the
      endoplasmic reticulum, where CE formation occurs. That CE levels are known to
      inversely correlate with both renal and nonrenal cell injury suggests the
      potential relevance of these observations to the induction phase of ischemic ARF.

PMID- 11318946
TI  - Monocyte chemoattractant protein-1 and osteopontin differentially regulate
      monocytes recruitment in experimental glomerulonephritis.
AB  - BACKGROUND: This study evaluated the mechanisms of monocyte/macrophage (M/M)
      infiltration in a rat model of anti-glomerular basement membrane
      glomerulonephritis (GN). We focused on chemokines and osteopontin, which are
      known regulators of M/M recruitment. METHODS: Using immunohistology, in situ
      hybridization, and Northern blotting, the expression levels of chemokines and
      osteopontin were evaluated in isolated glomeruli and tubules 4, 10, and 20 days
      after the induction of GN. In vivo blocking experiments were performed by
      application of neutralizing antibodies against osteopontin and monocyte
      chemoattractant protein-1 (MCP-1). RESULTS: In nephritic animals, high glomerular
      MCP-1 and RANTES (regulated upon activation normal T cell expressed and secreted)
      expression levels were observed on days 4 and 10. The tubular expression of MCP
      1, however, was only slightly enhanced. In contrast, tubular osteopontin
      production was maximally stimulated (day 10) and paralleled with peaks of
      albuminuria and tubulointerstitial M/M infiltration. Application of an anti
      osteopontin antibody ameliorated tubulointerstitial and glomerular M/M
      recruitment, whereas treatment with an anti-MCP-1 antibody selectively reduced
      glomerular M/M recruitment. However, tubulointerstitial M/M infiltration remained
      unchanged. CONCLUSION: These studies show that chemokines and osteopontin are
      differentially expressed in glomeruli and tubules in this model of GN. Chemokines
      play a primary role in the glomeruli, whereas osteopontin has a predominant role
      in tubulointerstitial M/M recruitment. The roles of chemokines and osteopontin
      may thus be dependent on the renal compartment and on the disease model.

PMID- 11318947
TI  - Role of alpha(3)beta(1) integrin in tubulogenesis of Madin-Darby canine kidney
      cells.
AB  - BACKGROUND: We isolated several Madin-Darby canine kidney (MDCK) subclones that
      exhibit different degrees of branching tubulogenesis in lower concentrations of
      collagen gel. The M634 clone formed cell aggregates in 0.3% collagen gel, but
      developed branching tubules vigorously in 0.1% collagen gel. In contrast, the
      Y224 clone formed cysts in 0.3% collagen gel and displayed fewer branching
      structures in 0.1% collagen gel. Morphologically, M634 cells exhibited higher
      levels of cell scattering as well as collagen-induced cell migration than Y224.
      We conducted this study to delineate the underlying mechanism of branching
      tubulogenesis in M634 cells. METHODS: Components of the focal contact machinery
      were analyzed in both cell lines, including the extracellular matrix
      glycoproteins fibronectin, laminin, and vitronectin; cytoskeleton-associated
      elements alpha-actinin, talin, and vinculin; and receptors for extracellular
      matrix and alpha(2), alpha(3), alpha(5), alpha(v), beta(1), and beta(3)
      integrins. Furthermore, we established several stable transfectants of alpha(3)
      integrin antisense RNA in M634 cells to examine the role of alpha(3)beta(1)
      integrin in branching morphogenesis directly. RESULTS: There were no obvious
      differences in levels of the focal adhesion complex proteins between M634 and
      Y224 cells, except that the content of the alpha(3) and beta1 integrins were 1.2-
      and 0.6-fold higher in M634 cells, respectively. The expression of alpha(3)
      integrin antisense RNA significantly lowered the levels of alpha(3) integrin mRNA
      and protein. The potential of cell scattering, migration, and branching
      tubulogenesis in M634 cells was inhibited according to the decrease in alpha(3)
      integrin expression. CONCLUSION: Our data indicate that expression of
      alpha(3)beta(1) integrin regulates cell scattering, migration, and branching
      tubulogenesis of MDCK cells, possibly via adhesion to or serving as a signaling
      molecule for type I collagen.

PMID- 11318948
TI  - Bcl-X(L) translocation in renal tubular epithelial cells in vitro protects distal
      cells from oxidative stress.
AB  - BACKGROUND: The molecular pathogenesis of different sensitivities of the renal
      proximal and distal tubular cell populations to ischemic injury, including
      ischemia-reperfusion (IR)-induced oxidative stress, is not well-defined. An in
      vitro model of oxidative stress was used to compare the survival of distal [Madin
      Darby canine kidney (MDCK)] and proximal [human kidney-2 (HK-2)] renal tubular
      epithelial cells, and to analyze for links between induced cell death and
      expression and localization of selected members of the Bcl-2 gene family (anti
      apoptotic Bcl-2 and Bcl-X(L), pro-apoptotic Bax and Bad). METHODS: Cells were
      treated with 1 mmol/L hydrogen peroxide (H2O2) or were grown in control medium
      for 24 hours. Cell death (apoptosis) was quantitated using defined morphological
      criteria. DNA gel electrophoresis was used for biochemical identification.
      Protein expression levels and cellular localization of the selected Bcl-2 family
      proteins were analyzed (Western immunoblots, densitometry, immunoelectron
      microscopy). RESULTS: Apoptosis was minimal in control cultures and was greatest
      in treated proximal cell cultures (16.93 +/- 4.18% apoptosis) compared with
      treated distal cell cultures (2.28 +/- 0.85% apoptosis, P < 0.001). Endogenous
      expression of Bcl-X(L) and Bax, but not Bcl-2 or Bad, was identified in control
      distal cells. Bcl-X(L) and Bax had nonsignificant increases (P> 0.05) in these
      cells. Bcl-2, Bax, and Bcl-X(L), but not Bad, were endogenously expressed in
      control proximal cells. Bcl-X(L) was significantly decreased in treated proximal
      cultures (P < 0.05), with Bax and Bcl-2 having nonsignificant increases (P>
      0.05). Immunoelectron microscopy localization indicated that control and treated
      but surviving proximal cells had similar cytosolic and membrane localization of
      the Bcl-2 proteins. In comparison, surviving cells in the treated distal cultures
      showed translocation of Bcl-X(L) from cytosol to the mitochondria after treatment
      with H2O2, a result that was confirmed using cell fractionation and analysis of
      Bcl-X(L) expression levels of the membrane and cytosol proteins. Bax remained
      distributed evenly throughout the surviving distal cells, without particular
      attachment to any cellular organelle. CONCLUSION: The results indicate that in
      this in vitro model, the increased survival of distal compared with proximal
      tubular cells after oxidative stress is best explained by the decreased
      expression of anti-apoptotic Bcl-X(L) in proximal cells, as well as translocation
      of Bcl-X(L) protein to mitochondria within the surviving distal cells.

PMID- 11318949
TI  - Induction and subcellular localization of protein kinase C isozymes following
      renal ischemia.
AB  - BACKGROUND: We have previously reported that the expression of the receptor for
      activated C kinase (RACK1) is induced post-ischemia/preperfusion injury to the
      kidney, and activation of protein kinase C (PKC) protects renal cells from
      hypoxic injury. This study was done to determine whether the induced expression
      of RACK1 is accompanied by changes in the level of expression and subcellular
      distribution of PKC isozymes. METHODS: Ischemia/reperfusion injury resulting in
      acute renal failure was induced by 60 minutes of bilateral renal artery clamping
      in rats. The expression levels and translocation of various PKC isozymes between
      soluble and particulate fractions in whole kidney homogenates were demonstrated
      by immunoblot analysis. The expression pattern of the various PKC isozymes in the
      kidney postinjury was performed by immunohistochemistry. RESULTS: PKC alpha, beta
      II, and zeta were induced and translocated from the soluble fraction to the
      particulate fraction post-injury. Immunolocalization showed PKC alpha, beta II,
      and zeta expression to be induced in the proximal tubule epithelial cell (PTEC)
      at 0 to 30 minutes post-ischemia/reperfusion injury (IRI). At one-day postinjury,
      the alpha isozyme was translocated to the plasma membrane of the undamaged PTEC,
      while it was translocated to the nucleus in damaged PTEC. PKC beta II expression
      was along the basal and lateral side of the undamaged PTEC, while it was
      distributed in the cytoplasm of sloughed cells in the damaged PTEC. PKC zeta
      expression at one day was along the apical side of the damaged PTEC. At seven
      days postinjury, the expressions of the alpha and zeta isozymes were localized to
      the plasma membrane of the regenerating PTEC and the expression of PKC beta II
      isozyme to certain interstitial cells. CONCLUSION: The induced expression,
      translocation, and the intracellular spatial distributions of the enzymes suggest
      that they may mediate multiple processes during IRI.

PMID- 11318950
TI  - Induction of stress response proteins and experimental renal
      ischemia/reperfusion.
AB  - BACKGROUND: The induction of stress response (heat shock) proteins (HSPs) is a
      highly conserved response that protects many cell types from diverse
      physiological and environmental stressors. We tested the hypothesis that the
      induction of HSPs is protective in experimental renal ischemia/reperfusion
      injury. METHODS: The effect of prior heat stress was examined in a rat model of
      renal ischemia. Postischemic renal function, histopathology, myeloperoxidase
      activity, and mortality were determined in hyperthermia and sham hyperthermia
      groups. RESULTS: HSP84, HSP70, and HSP22 mRNA were increased after eight minutes
      but not four minutes of hyperthermia. The induction of HSP84 and HSP70 was
      blocked by pretreatment with quercetin. Improvement in renal function, mortality,
      and histologic abnormalities was seen with eight minutes of hyperthermia six
      hours before ischemia. Protection was dependent on the timing of ischemia
      relative to heat stress and was not observed when HSPs were not induced.
      Postischemic increases in renal myeloperoxidase activity were markedly attenuated
      in the hyperthermia compared with the sham hyperthermia group. CONCLUSION:
      Endogenous protective mechanisms may be important in renal ischemia/reperfusion
      injury.

PMID- 11318951
TI  - Functional heterogeneity of ROMK mutations linked to hyperprostaglandin E
      syndrome.
AB  - BACKGROUND: The renal K(+) channel ROMK (Kir1.1) controls salt reabsorption in
      the kidney. Loss-of-function mutations in this channel cause hyperprostaglandin E
      syndrome/antenatal Bartter syndrome (HPS/aBS), which is characterized by severe
      renal salt and fluid wasting. METHODS: We investigated 10 HPS/aBS patients for
      mutations in the ROMK gene by single-strand conformation polymorphism analysis
      (SSCA) and direct sequencing. To assess the functional consequences, Ba(2+)
      sensitive K(+) currents were measured in five mutants of the core region as well
      as one mutant with truncated C-terminus, using the two-electrode voltage-clamp
      technique after an injection of mutant cRNA into Xenopus oocytes. RESULTS: Three
      novel ROMK mutations were identified together with six mutations described
      previously. The mutations were categorized into three groups: (1) amino acid
      exchanges in the core region (M1-H5-M2), (2) truncation at the cytosolic C
      terminus, and (3) deletions of putative promoter elements. While the core
      mutations W99C, N124K, and I142T led to significantly reduced macroscopic K(+)
      currents (1 to 8% of wild-type currents), the A103V and P110L variants retained
      substantial K(+) conductivity (23 and 35% of wild-type currents, respectively).
      Coexpression of A103V and P110L, resembling the compound heterozygous state of
      the affected individual, further reduced macroscopic currents to 9% of the wild
      type currents. All mutants in the core region exerted a dominant-negative effect
      on wild-type ROMK1. The C-terminal frameshift (fs) mutation (H354fs) did not
      change current amplitudes compared with ROMK1 wild type, suggesting that a
      mechanism other than alteration of the electrophysiological properties may
      responsible for loss of channel activity. CONCLUSIONS: Analysis of ROMK mutants
      linked to HPS/aBS revealed a spectrum of mechanisms accounting for loss of
      channel function. Further characterization of the molecular defects might be
      helpful for the development of new therapeutic approaches.

PMID- 11318952
TI  - Regulation of ROMK and channel-inducing factor (CHIF) in acute renal failure due
      to ischemic reperfusion injury.
AB  - BACKGROUND: Acute renal failure caused by ischemia followed by reperfusion is
      often associated with severe hyperkalemia. The present study was undertaken to
      characterize the effects of renal ischemia and reperfusion on plasma potassium
      (K) and on the gene expression of channel-inducing factor (CHIF), a putative K
      channel regulator, and of ROMK, the distal nephron secretory K channel. METHODS:
      The following groups of rats were studied: (1) sham operated (sham); (2) after
      one hour of ischemia by bilateral renal artery clamping (I), and after one hour
      of ischemia; (3) one hour of reperfusion (I-R 1 h); (4) 24 hours of reperfusion
      (I-R 24 h); (5) 48 hours of reperfusion (I-R 48 h); and (6) 72 hours reperfusion
      (I-R 72 h). The expression of CHIF and ROMK was examined by Northern blot
      hybridization in renal cortex, medulla, and papilla and in the colon. The
      abundance of ROMK protein was determined in the renal cortex and medulla by
      immunoblotting. RESULTS: Maximal plasma creatinine and potassium levels after
      ischemia and reperfusion were 470 +/- 16 micromol/L, P < 0.0001 versus sham, and
      9.65 +/- 0.33 mmol/L, P < 0.0001 versus sham, respectively. The expression of
      CHIF was significantly down-regulated in the medulla and papilla, with a maximal
      decrease of 80% at 48 to 72 hours. In contrast, a most significant increase in
      CHIF mRNA expression (250% of baseline) was noted in the colon after 24 to 48
      hours of reperfusion. ROMK expression was reduced in the cortex and was
      completely abolished in the medulla at 48 to 72 hours of reperfusion. Ischemia
      and reperfusion injury significantly decreased ROMK protein abundance to 10% of
      control in the medullary fractions. CONCLUSIONS: These results suggest that down
      regulation of renal CHIF and ROMK may contribute at least partly to the
      hyperkalemia of acute renal failure after ischemia and reperfusion, while CHIF up
      regulation in the colon may act as a compensatory mechanism of maintaining K
      balance via increased K secretion.

PMID- 11318953
TI  - Human cystinuria-related transporter: localization and functional
      characterization.
AB  - BACKGROUND: Cystinuria has been proposed to be an inherited defect of apical
      membrane transport systems for cystine and basic amino acids in renal proximal
      tubules. Although the mutations of the recently identified transporter
      BAT1/b(0,+)AT have been related to nontype I cystinuria, the function and
      localization of human BAT1 (hBAT1)/b(0,+)AT have not been well characterized.
      METHODS: The cDNA encoding hBAT1 was isolated from human kidney. Fluorescence in
      situ hybridization was performed to map the hBAT1 gene on human chromosomes.
      Tissue distribution and localization of expression were examined by Northern blot
      and immunohistochemical analyses. hBAT1 cDNA was transfected to COS-7 cells with
      rBAT cDNA, and the uptake and efflux of 14C-labeled amino acids were measured to
      determine the functional properties. The roles of protein kinase-dependent
      phosphorylation were investigated using inhibitors or activators of protein
      kinases. RESULTS: The hBAT1 gene was mapped to 19q12-13.1 on the human
      chromosome, which is the locus of nontype I cystinuria. hBAT1 message was
      expressed predominantly in kidney. hBAT1 protein was localized in the apical
      membrane of proximal tubules in human kidney. When expressed in COS-7 cells with
      a type II membrane glycoprotein rBAT (related to b(0,+)-amino acid transporter),
      hBAT1 exhibited the transport activity with the properties of amino acid
      transport system b(0,+), which transported cystine as well as basic and neutral
      amino acids presumably via a substrate exchange mechanism. BAT1-mediated
      transport was reduced by the protein kinase A activator and enhanced by the
      tyrosine kinase inhibitor. CONCLUSIONS: hBAT1 exhibited the properties expected
      for a transporter subserving the high-affinity cystine transport system in renal
      proximal tubules. The hBAT1 gene was mapped to the locus of nontype I cystinuria,
      confirming the involvement of hBAT1 in cystinuria.

PMID- 11318954
TI  - Creatinine clearance, pulse wave velocity, carotid compliance and essential
      hypertension.
AB  - BACKGROUND: The vascular hallmark of subjects with end-stage renal disease is
      increased arterial stiffness independent of blood pressure, wall stress, and
      cardiovascular risk factors such as hypertension, plasma glucose and cholesterol,
      obesity, and tobacco consumption. Whether arterial stiffness and kidney function
      are statistically associated in subjects with plasma creatinine < or =130
      micromol/L has not yet been determined. Material. In 1290 subjects with normal or
      elevated blood pressure values and plasma creatinine < or =130 micromol/L,
      subjects were divided into three tertiles according to the calculated creatinine
      clearance. Blood pressure, aortic pulse wave velocity (PWV), and standard
      cardiovascular risk factors were determined in parallel. In 112 of the
      hypertensive subjects, common carotid and radial artery structure and function
      (high-resolution echo-Doppler techniques) also were measured. RESULTS: From the
      1290 subjects, only the low-tertile group presented a significant negative
      association between PWV and creatinine clearance independently of blood pressure
      and standard risk factors. This association was stronger in subjects < or =55
      years of age. In the 112 hypertensive subjects, carotid compliance was positively
      correlated to creatinine clearance even after an adjustment for age, gender, and
      blood pressure. At less than 55 years of age, creatinine clearance represented
      20% of the variance of carotid compliance. Such findings were not observed for
      radial artery compliance. CONCLUSION: Increased stiffness of central arteries is
      statistically associated with reduced creatinine clearance in subjects with mild
      to-moderate renal insufficiency, indicating that kidney alterations may interact
      not only with small but also large arteries, and this is independent of age,
      blood pressure, and standard risk factors.

PMID- 11318955
TI  - Long-term exposure to high glucose up-regulates VCAM-induced endothelial cell
      adhesiveness to PBMC.
AB  - BACKGROUND: The changes induced on endothelial cells by a long-term exposure to
      high glucose, a situation that mimics the hyperglycemia of diabetics, have not
      yet been determined. We compared short- and long-term effects of elevated glucose
      on macrovascular and microvascular endothelial cells. METHODS: Endothelial cells
      were grown in high-glucose media for 24 hours and for 8 weeks. Cell proliferation
      was evaluated by cell counting, apoptosis and expression of adhesion molecules by
      flow cytometry; nitric oxide (NO) by measuring the concentration of
      nitrite/nitrate in the cell supernatant; alpha 2(IV) collagen mRNA and protein by
      reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent
      assay, respectively. The adhesion of peripheral blood mononuclear cells (PBMCs)
      to endothelial cells was evaluated by adhesion assay. In some experiments,
      endothelial cells were preincubated with anti-vascular cell adhesion molecule-1
      (VCAM-1) and anti-receptor for advanced glycation end product (RAGE) blocking
      antibodies. RESULTS: At 24 hours, but not at 8 weeks, high glucose increased
      endothelial cell proliferation and apoptosis. High glucose did not modify NO
      synthesis at 24 hours and 8 weeks. Collagen production and expression were
      increased only after eight weeks. VCAM-1 but not intercellular adhesion molecule
      1 was up-regulated after 8 weeks, a change not observed after 24 hours. The
      adhesion of PBMCs was significantly increased at eight weeks and was completely
      abrogated by anti--VCAM-1 and by anti-RAGE antibodies. After 24 hours, there was
      a modest increase of PBMC adhesion that was not blunted by anti-RAGE antibodies.
      CONCLUSIONS: Increased adhesion of PBMCs, caused by up-regulation of VCAM-1 with
      a mechanism involving advanced glycation end product (AGE) adducts, and augmented
      collagen deposition are critical effects of long-term high glucose on endothelial
      cells, and may eventually promote the atherosclerotic process.

PMID- 11318956
TI  - Chronic potassium depletion induces renal injury, salt sensitivity, and
      hypertension in young rats.
AB  - BACKGROUND: Chronic hypokalemia has been associated with renal hypertrophy,
      interstitial disease, and hypertension in both adult animals and humans. However,
      the effects of potassium (K(+)) depletion on the rapidly growing infant have not
      been well studied. The purpose of this study was to determine the effects of
      severe chronic dietary K(+) depletion on blood pressure (BP) and renal structural
      changes in young rats. METHODS: Sprague-Dawley rats (50 +/- 5 g) were fed either
      a control or a potassium-deficient diet (<0.05% K(+)) for 14 to 21 days. At the
      end of this period, the blood pressure (BP) was measured in all rats, and six
      rats in each group were sacrificed to determine changes in renal histology and
      renin-angiotensin system (RAS) activity. The remaining rats in each group were
      then switched to a high-salt (6% NaCl)--normal-K(+) (0.5%) diet or were continued
      on their respective control or K(+)-deficient diet for an additional six days.
      Blood pressure measurements were done every three days until the end of the
      study. RESULTS: K(+)-depleted animals had significant growth retardation and
      increased RAS activity, manifested by high plasma renin activity, recruitment of
      renin-producing cells along the afferent arterioles, and down-regulation of
      angiotensin II receptors in renal glomeruli and ascending vasa rectae. K(+)
      depleted kidneys also showed tubulointerstitial injury with tubular cell
      proliferation, osteopontin expression, macrophage infiltration, and early
      fibrosis. At week 2, K(+)-depleted rats had higher systolic BP than control rats.
      Switching to a high-salt (6% NaCl)--normal-K(+) diet resulted in further
      elevation of systolic BP in K(+)-depleted rats, which persisted even after the
      serum K(+) was normalized. CONCLUSION: Dietary potassium deficiency per se
      increases the BP in young rats and induces salt sensitivity that may involve at
      least two different pathogenic pathways: increased RAS activity and induction of
      tubulointerstitial injury.

PMID- 11318957
TI  - The SOD mimetic tempol restores vasodilation in afferent arterioles of
      experimental diabetes.
AB  - BACKGROUND: Endothelium-dependent vasodilation is impaired in large conduit
      vessels in diabetes mellitus. Oxygen radicals contribute to the impaired
      endothelium-dependent vasodilation. We tested the hypothesis that stimulated
      endothelium-dependent vasodilation is reduced in renal afferent arterioles in
      diabetes and is caused by an increase in vascular superoxide (O2(-)). METHODS:
      Renal afferent arterioles from normal and insulin-treated alloxan-diabetic
      rabbits were microdissected and microperfused in vitro for the study of luminal
      diameter responses to acetylcholine (Ach; 10(-11) to 10(-6) mol/L). The blood
      glucose concentration of insulin-treated alloxan-diabetic rabbits was elevated
      fourfold compared with normal rabbits (319 +/- 23 vs. 79 +/- 6 mg/dL, P < 0.001).
      RESULTS: In norepinephrine (NE)-preconstricted afferent arterioles of normal
      rabbits, Ach significantly (P < 0.001) increased luminal diameter by 165 +/- 44%.
      The nitric oxide synthase inhibitor N(omega)-nitro-L-arginine methyl ester (10(
      4) mol/L) blocked this Ach-induced vasodilation. In marked contrast, in NE
      preconstricted arterioles of diabetic rabbits, Ach significantly (P < 0.01)
      decreased luminal diameter by 41 +/- 11%. Pretreatment of diabetic afferent
      arterioles with the superoxide dismutase (SOD) mimetic tempol (10(-3) mol/L)
      restored a vasodilator response to Ach. In NE-preconstricted diabetic afferent
      arterioles treated with tempol, Ach significantly (P < 0.001) increased luminal
      diameter by 25 +/- 6%. CONCLUSIONS: Ach-induced afferent arteriolar vasodilation
      is dependent on nitric oxide and is impaired in diabetes. O2(-) contributes to
      the impaired Ach-induced vasodilation in renal afferent arterioles in diabetes.

PMID- 11318958
TI  - Salt sensitivity in genetically hypertensive rats of the Lyon strain.
AB  - BACKGROUND: Genetically hypertensive (LH) rats of the Lyon strain exhibit a
      blunted pressure-natriuresis function when compared, in acute conditions, with
      their normotensive (LN) and low blood pressure (LL) controls. The present work
      was aimed to determine whether LH rats were salt sensitive in chronic conditions.
      In addition, a protocol was developed to determine the renal function curve in
      freely moving rats. METHODS: Fourteen-week-old rats either untreated or orally
      treated since weaning with perindopril (3 mg/kg/24 h), an angiotensin-converting
      enzyme inhibitor, or with valsartan (15 mg/kg/24 h), an angiotensin II subtype 1
      receptor antagonist, so as to eliminate the influence of endogenous changes in
      angiotensin formation were used. Blood pressure (BP) and urinary sodium excretion
      were measured before, during an oral salt load (2% NaCl in drinking water), and
      during a two-week aldosterone infusion (50 microg/kg/24 h subcutaneously).
      RESULTS: NaCl induced a greater BP increase in untreated LH rats than in LN and
      LL controls. Perindopril normalized the BP of LH rats but not its elevation
      during a salt load. Aldosterone slightly increased BP in LH and LL rats either
      untreated or treated with valsartan. Finally, the combination of telemetric BP
      measurement with 24-hour urine collection when salt was added to drinking water
      allowed accurate determination of the slope of the chronic renal function curve
      in freely moving rats. CONCLUSION: The present work demonstrates that LH rats are
      salt sensitive. This characteristic manifests despite the lack of an active renin
      angiotensin system and is not explained by a hypersensitivity to aldosterone.

PMID- 11318959
TI  - Circadian rhythms in systemic hemodynamics and renal function in healthy subjects
      and patients with nephrotic syndrome.
AB  - BACKGROUND: The resemblance of the circadian rhythm of glomerular filtration rate
      (GFR) to that of arterial blood pressure (BP) suggests that systemic hemodynamic
      factors contribute to this variation. In the present study, this was investigated
      using continuous BP monitoring and pulse wave analysis. The study was performed
      in eight healthy subjects and in seven patients with nephrotic syndrome who had
      normal or reversed rhythms of GFR. METHODS: Circadian variations of renal
      function (continuous infusion of inulin/paraaminohippuric acid), noninvasive
      finger arterial pressure (Portapres), and vasoactive hormone levels were
      monitored during 27 hours. With stepwise backward regression analysis, the
      contributions of the measured variables to the circadian variation of GFR were
      investigated. RESULTS: Both groups showed a reduction of BP at night. In the
      controls, this was related to a drop in cardiac output, while in the patients,
      total peripheral resistance decreased at night. None of the hemodynamic variables
      explained the circadian GFR variation in both groups. In the controls, only 6% of
      the effective renal plasma flow (ERPF) rhythm was associated with variations in
      cardiac output (P = 0.03). In the patients, atrial natriuretic peptide and plasma
      renin activity were responsible for 36% of the variation in GFR (P < 0.01).
      CONCLUSIONS: These results indicate that the circadian variation of GFR does not
      result directly from changes in BP or cardiac output. An inverted GFR rhythm in
      patients with nephrotic syndrome may originate from hormonal mechanisms rather
      than directly from the hemodynamic effects of edema mobilization.

PMID- 11318960
TI  - Coordinate regulation of canine glomeruli and adrenal angiotensin receptors by
      dietary sodium manipulation.
AB  - BACKGROUND: This study evaluated the effects of dietary sodium manipulation in
      dogs on the regulation of canine angiotensin receptors (cAT1 and cAT2) in the
      kidney and adrenal. METHODS: Isolated glomeruli and membranes from renal medulla
      and the adrenal gland were used in radioligand binding assays from two groups of
      dogs: dogs maintained on low-sodium diet for two weeks followed by a high-sodium
      diet for two weeks (H), and dogs were maintained on the reverse schedule (L).
      RESULTS: Analysis of the binding data showed that dietary sodium manipulation had
      no significant effects on cAT1 and cAT2 receptor binding affinities in glomeruli,
      renal medulla, and adrenal tissues. In contrast, dietary sodium loading induced a
      marked increase in cAT1 receptor expression in both the glomeruli and adrenal
      compared with receptor expression in salt-restricted animals [H/L ratio:
      glomeruli (1.5), renal medulla (1.1), adrenal (1.6)] that inversely correlated
      with the activity of the plasma renin angiotensin system. Conversely, adrenal
      cAT2 receptor expression was regulated in an inverse manner in the H and L animal
      groups [H/L ratio: 0.7]. CONCLUSIONS: This study demonstrates that renal
      glomerular and adrenal AT1 receptors in the dog are coordinately down-regulated
      by dietary sodium restriction compared with sodium loading, which is distinctly
      different from the reciprocal regulation observed for rat AT1 receptors in these
      tissues. Collectively, these data suggest that postreceptor events in dogs are
      determinants of the aldosterone response observed during sodium restriction.
      These findings have important implications for the regulation of the renin
      angiotensin system in humans, and suggest that coordinate regulation of AT1
      receptors in the adrenal and glomeruli represent a negative feedback mechanism
      that when functioning normally prevents fluctuations of arterial blood pressure
      and development of arterial hypertension in response to changes in dietary
      sodium.

PMID- 11318961
TI  - Production of cysteinyl-dopamine during intravenous dopamine therapy.
AB  - BACKGROUND: Oxidized dopamine rapidly forms thiol-conjugates with --SH groups on
      cysteine, glutathione, and proteins. We used cysteinyl-dopamine production as an
      index of thioester production during intravenous dopamine treatment of critically
      ill patients. METHODS: Cysteinyl-dopamine and catecholamines were measured by
      high-performance liquid chromatography with electrochemical detection. The
      production of cysteinyl-dopamine by purified human neutrophils was measured using
      dopamine (1 micromol/L) and cysteine (1 mmol/L) concentrations similar to those
      found during dopamine treatment. To examine the impact of endotoxic shock on
      cysteinyl-dopamine production, anesthetized rats were given dopamine (12 to 15
      microg/kg/min intravenously) with or without endotoxin (50 mg/kg intravenously).
      RESULTS: In vitro, neutrophils converted 26% of dopamine to cysteinyl-dopamine
      (30 min at 37 degrees C). Activating neutrophils with zymogen increased dopamine
      consumption from 26 to 68%, but only 36% appeared as cysteinyl-dopamine. The
      remainder may have been oxidized to other cysteinyl derivatives. Endotoxin
      increased cysteinyl-dopamine in rat plasma from 2.5 nmol/L (range <0.2 to 11) to
      9.7 nmol/L (range <0.3 to 31, P = 0.1). After four hours, with or without
      endotoxin, cysteinyl-dopamine was <0.3 nmol/L in cerebrospinal fluid. In the
      plasma of eight patients receiving dopamine (6 to 20 microg/kg/min for 1 to 3
      days), dopamine was 0.5 to 9.9 micromol/L, and cysteinyl-dopamine was 48 to 1660
      nmol/L. Cysteinyl-dopamine was 4.3 to 22.6% of dopamine and correlated with
      leukocyte count (r(2) = 0.388, P = 0.099). CONCLUSIONS: A significant fraction of
      exogenously administered dopamine reacts with -SH groups of cysteine and probably
      also with -SH groups on peptides and proteins. During brief dopamine treatment of
      endotoxic shock in rats, neither dopamine nor cysteinyl-dopamine crossed the
      blood-brain barrier.

PMID- 11318962
TI  - Peroxisome proliferator-activated receptor-gamma agonist troglitazone protects
      against nondiabetic glomerulosclerosis in rats.
AB  - BACKGROUND: Peroxisome proliferator-activated receptor-gamma (PPAR gamma) is a
      member of the nuclear receptor superfamily of ligand-dependent transcriptional
      factors with beneficial effects in diabetes mediated by improved insulin
      sensitivity and lipid metabolism, but potential adverse effects in
      atherosclerosis by promoting in vitro foam cell formation. We explored whether a
      PPAR gamma agonist, troglitazone (TGL), affects sclerosis by mechanisms unrelated
      to insulin and lipid effects in a model of nondiabetic glomerulosclerosis.
      METHODS: Adult male Sprague Dawley rats underwent 5/6 nephrectomy and were
      treated for 12 weeks as follows: control (CONT), no further treatment; triple
      antihypertensive therapy (TRX); and TGL or TGL + TRX. Functional, morphological,
      and molecular analyses were performed. RESULTS: Systolic blood pressure (SBP) was
      increased in CONT and TGL groups (161 +/- 1 and 160 +/- 3 mm Hg), but not in TGL
      + TRX and TRX (120 +/- 3 vs. 126 +/- 1 mm Hg, P < 0.0001 vs. non-TRX). Serum
      triglyceride and cholesterol levels in all groups remained normal except for
      slightly higher serum cholesterol levels in TRX group. TGL groups had reduced
      proteinuria, serum creatinine, and glomerulosclerosis versus CONT, in contrast to
      no significant effect with TRX alone (sclerosis index, 0 to 4+ scale: CONT 1.99
      +/- 0.42, TGL 0.85 +/- 0.12, TGL + TRX 0.56 +/- 0.14, TRX 1.30 +/- 0.21; TGL, P <
      0.05; TGL + TRX, P = 0.01 vs. CONT). Glomerular cell proliferation, assessed by
      proliferating cell nuclear antigen (PCNA), was decreased after treatment with TGL
      or TGL + TRX, in parallel with decreases in glomerular p21 mRNA and p27 protein
      compared with CONT and TRX (PCNA + cells/glomerulus: CONT 2.04 +/- 0.64, TGL 0.84
      +/- 0.21, TGL + TRX 0.30 +/- 0.07, TRX 1.38 +/- 0.37; TGL, P < 0.05, TGL + TRX, P
      < 0.01 vs. CONT). Glomerular plasminogen activator inhibitor-1 (PAI-1)
      immunostaining was decreased in TGL or TGL + TRX groups (0 to 4+ scale, CONT 2.42
      +/- 0.32, TGL 1.40 +/- 0.24, TGL + TRX 1.24 +/- 0.17, TRX 2.53 +/- 0.24; TGL or
      TGL + TRX vs. CONT, P < 0.05), with a parallel decrease in PAI-1 mRNA by in situ
      hybridization. Glomerular and tubular transforming growth factor-beta (TGF-beta)
      mRNA expression was decreased with TGL treatment. Glomerular macrophages, present
      in CONT and TRX rats, did not express PPAR gamma, in contrast to PPAR gamma +
      macrophages in control carotid artery plaque. PPAR gamma was expressed in
      resident cells. CONCLUSIONS: Our results demonstrate in vivo that the PPAR gamma
      ligand TGL ameliorates the progression of glomerulosclerosis in a nondiabetic
      model. Macrophages show phenotypic diversity in glomerular versus vascular
      sclerosis, with macrophage PPAR gamma expression in only the latter. PPAR gamma
      beneficial effects are independent of insulin/glucose effects and are associated
      with regulation of glomerular cell proliferation, hypertrophy, and decreased PAI
      1 and TGF-beta expression.

PMID- 11318963
TI  - Novel glomerular lipoprotein deposits associated with apolipoprotein E2
      homozygosity.
AB  - BACKGROUND: Hyperlipoproteinemia is occasionally associated with severe
      glomerular injury caused by abnormal accumulation of lipid in glomeruli, which
      occurs in conditions such as lipoprotein glomerulopathy (LPG). This study
      investigates the cases of two siblings with homozygous apolipoprotein (apo) E2
      who show unique histologic features, massive proteinuria, and
      dysbetalipoproteinemia. METHODS: Histologic studies were performed using renal
      biopsy specimens. Plasma lipoproteins were extensively characterized. The exons
      of the apo E genes were sequenced to avoid missing any mutations. RESULTS:
      Histologically, the siblings' condition resembled LPG by light microscopy
      studies. Electron microscopy studies revealed large lipoid deposits in the
      paramesangium, subendothelium, and subepithelium of the glomeruli, which were
      different from LPG in terms of not forming the layered structure resembling a
      fingerprint even in large lipoprotein thrombi, and mesangial foam cells.
      Immunohistochemically, the lipoid deposits contained apo E and apo B. These
      patients did not have either diabetic nephropathy or other known forms of
      glomerulonephritis. The sequence of exons of the apo E genes revealed
      homozygosity for apo E2 in both cases. CONCLUSION: The extensive lipoprotein
      deposition in glomeruli, which resembles LPG, can also occur in apo E2 homozygous
      individuals, but in a distinct fashion. Because the two cases were siblings, they
      may have other shared alleles, in addition to the apo E2 allele, that negatively
      affect processing of lipoproteins and lead to abnormal accumulation of
      lipoprotein deposits in glomeruli.

PMID- 11318964
TI  - Immunosuppressive agents in childhood nephrotic syndrome: a meta-analysis of
      randomized controlled trials.
AB  - BACKGROUND: Many children with steroid-sensitive nephrotic syndrome (SSNS)
      relapse frequently and receive immunosuppressive agents. In this systematic
      review of randomized controlled trials (RCTs), the benefits and harms of these
      immunosuppressive agents are evaluated. METHODS: RCTs with outcome data at six
      months or more that evaluated noncorticosteroid agents in relapsing SSNS were
      included. A summary relative risk for relapse at 6 to 12 months was calculated
      using a random effects model. RESULTS: Seventeen trials involving 631 children
      were identified. Cyclophosphamide [3 trials; relative risk (RR) 0.44, 95%
      confidence interval (CI), 0.26 to 0.73] and chlorambucil (2 trials; RR 0.13, 95%
      CI, 0.03 to 0.57) significantly reduced the relapse risk at 6 to 12 months
      compared with prednisone alone. In the single chlorambucil versus
      cyclophosphamide trial, there was no observed difference in relapse risk at two
      years (RR 1.31, 95% CI, 0.80 to 2.13). Cyclosporine was as effective as
      cyclophosphamide (1 trial; RR 1.07, 95% CI, 0.48 to 2.35) and chlorambucil (1
      trial; RR 0.82, 95% CI, 0.44 to 1.53), but the effect was not sustained when
      cyclosporine was ceased. During treatment, levamisole (3 trials; RR 0.60, 95% CI,
      0.45 to 0.79) was more effective than steroids alone, but the effect was not
      sustained. CONCLUSIONS: Cyclophosphamide, chorambucil, cyclosporine, and
      levamisole reduce the risk of relapse in children with relapsing SSNS compared
      with prednisone alone. Clinically important differences in efficacy among these
      agents are possible, and further comparative trials are still needed. Meanwhile,
      the choice between these agents depends on physician and patient preferences
      related to therapy duration and complication type and frequency.

PMID- 11318965
TI  - Plasma concentration and urinary excretion of N-terminal proatrial natriuretic
      peptides in patients with kidney diseases.
AB  - BACKGROUND: Biologically active N-terminal fragments such as proANP(1-30),
      proANP(31-67), and proANP(1-98) derive from the prohormone of alpha-human atrial
      natriuretic peptide [proANP(99-126) or alpha-ANP]. No systematic data are
      available for patients with different kidney diseases. METHODS: Specific
      immunoassays were developed to determine plasma and urine concentrations of these
      fragments in 121 patients with different degrees of kidney function and urinary
      protein excretion, respectively. RESULTS: In patients with kidney disease and
      normal renal function without proteinuria, circulating proANP(1-30) and proANP(31
      67) increased 2.8-fold and 6.5-fold, respectively. Urinary excretion of proANP(31
      67) increased by a factor of 7.7 in these patients, whereas proANP(1-30) was not
      affected. Patients with impaired renal function had a dramatic increase of
      urinary proANP(31-67) excretion even before serum creatinine levels started to
      rise. The progression of renal failure caused a significant rise of circulating
      proANP(1-30) (4.3-fold) and proANP(31-67) (3.0-fold) compared with patients with
      normal renal function. Urinary excretion of proANP peptides significantly
      increased, particularly when the serum creatinine level was> 5.0 mg/dL [proANP(1
      30) 26-fold, proANP(31-67) 8.4-fold]. Urinary excretion of proANP(1-30) increased
      up to 4.4-fold and urinary excretion of proANP(31-67) increased up to 2.4-fold in
      patients with proteinuria in excess of 3 g/24 h. CONCLUSIONS: Plasma
      concentrations and urinary excretion of proANP(1-30) and proANP(31-67) are
      affected by kidney disease and function, but not by proteinuria per se. It is
      proposed that the diseased kidney increases early urinary excretion of proANP
      fragments to participate in the regulation of renal function as well as sodium
      and water excretion.

PMID- 11318966
TI  - A randomized trial of minidose warfarin for the prevention of late malfunction in
      tunneled, cuffed hemodialysis catheters.
AB  - BACKGROUND: Minidose warfarin (1 mg/day) has been associated with a 74% reduction
      in the thrombosis rate of central venous catheters used in oncology patients. To
      determine the efficacy of minidose warfarin on late malfunction caused by
      thrombosis or fibrin sheath formation in tunneled, cuffed catheters (TCC) used
      for hemodialysis (HD), we performed a randomized, placebo-controlled trial.
      METHODS: One hundred five chronic HD patients with TCCs were initially
      randomized. Of these, 85 (warfarin 41 and placebo 44) completed the first two
      weeks of the protocol and were followed for the first year of TCC life or until
      TCC removal. RESULTS: Sixteen TCCs failed with late TCC malfunction, eight in
      each group. In a multivariate analysis, there was no significant effect of
      warfarin on thrombosis-free TCC survival or time to the first urokinase (UK)
      instillation for incipient thrombosis. The presence of a low hemoglobin (Hgb;
      <10.5 g/dL) or a low international normalized ratio (INR; <1.00) was
      significantly associated with a higher risk of late TCC malfunction (RR 5.2 and
      4.0, respectively), a higher risk of incipient TCC thrombosis requiring UK (RR
      2.0 and 2.8, respectively), and higher rates of UK dosing. Diabetics had a 3.6
      fold higher risk of late TCC malfunction and a twofold higher risk of incipient
      thrombosis requiring UK, although these findings were not statistically
      significant. Aspirin use, race, age, number of hospitalizations, erythropoietin
      dose, intradialytic heparin dose, serum albumin, and the number of episodes of
      TCC-associated infection were not significantly associated with late TCC
      malfunction. CONCLUSIONS: Thrombosis prophylaxis using fixed minidose warfarin is
      not efficacious in TCCs used for HD. However, the present data suggest improved
      TCC survival in patients with an INR> 1.00. Patients with diabetes and those with
      a low Hgb or INR have a higher risk of late TCC malfunction.

PMID- 11318967
TI  - Oxidative stress is reduced by the long-term use of vitamin E-coated dialysis
      filters.
AB  - BACKGROUND: Oxidative stress during hemodialysis is thought to promote the
      progression of vascular complications in hemodialysis patients. The protective
      role of vitamin E as a lipophilic antioxidant against oxidative stress has been
      widely investigated. Here we investigated the effects of a vitamin E-coated
      regenerated cellulose hollow fiber dialyzer (CL-EE) on oxidative stress compared
      with a polysulfone hollow fiber (CL-PS). METHODS: For at least three months
      before beginning the protocol, 10 nondiabetic (NDM) patients (70.0 +/- 7.5 years;
      6 males and 4 females) and 8 diabetic (DM) patients (65.0 +/- 7.4 years; 4 males,
      4 females) were dialyzed with CL-PS. After that, we treated all of the patients
      with CL-EE for six months. Malondialdehyde (MDA), advanced glycation end products
      (AGEs), and 8-hydroxydeoxyguanosine (8-OHdG) were monitored as biomarkers for
      oxidative stress at the start and then at one, three, and six months into
      treatment with CL-EE. RESULTS: Serum MDA, AGE, and 8-OHdG levels increased after
      the hemodialysis with CL-PS. The increase of the biomarkers was completely
      prevented by a single use of CL-EE. Long-term hemodialysis with CL-EE for six
      months significantly reduced the basal levels of the oxidant markers at one month
      for AGE and at six months for 8-OHdG in both DM and NDM patients. Serum MDA was
      reduced in only DM patients at three months. The improvement of the oxidative
      stress with CL-EE was more prominent in the DM patients. CONCLUSIONS: Long-term
      treatment with CL-EE efficiently improves the oxidative stress associated with
      hemodialysis and potentially reduces dialysis complications due to oxidative
      stress.

PMID- 11318968
TI  - beta(2)-Microglobulin increases the expression of vascular cell adhesion molecule
      on human synovial fibroblasts.
AB  - BACKGROUND: beta(2)-Microglobulin (beta(2)m) amyloidosis is a destructive
      articular disease that affects patients on dialysis. The disease presentation is
      similar to other forms of arthritis in which adhesion molecules are felt to be
      pathogenic. Therefore, we hypothesized that beta(2)m directly increases the
      expression of vascular cell adhesion molecule-1 (VCAM-1) by synovial fibroblasts.
      We also examined the effect of alteration of beta(2)m by advanced glycation end
      products on this cellular response. METHODS: Human synovial fibroblasts were
      isolated and incubated with beta(2)m with and without alteration with advanced
      glycation end products. VCAM-1 expression was determined by immunohistochemistry,
      flow cytometry, and Western blot and Northern blot analyses. RESULTS: beta(2)m
      increased the protein expression of VCAM-1 by synovial fibroblasts in a dose
      dependent manner. beta(2)m altered with advanced glycation end products had no
      effect. However, all forms of beta(2)m increased VCAM-1 mRNA. beta(2)m also
      increased the adhesion of peripheral blood mononuclear cells to synovial
      fibroblasts. CONCLUSION: beta2m directly increases the expression of VCAM-1 by
      synovial fibroblasts, indicating that synovial fibroblasts may play a key role in
      the pathogenesis of beta(2)m amyloidosis.

PMID- 11318970
TI  - Acute effects of simultaneous intraperitoneal infusion of glucose and amino
      acids.
AB  - BACKGROUND: The feasibility of simultaneously infusing glucose and amino acid
      (AA)-based peritoneal dialysis solutions was tested to determine whether
      peritoneal dialysis patients could achieve an adequate nonprotein
      calorie/nitrogen ratio while preventing a marked increase in blood urea nitrogen
      (BUN), which is usually seen if the AAs are administered without glucose.
      METHODS: An automatic peritoneal dialysis cycler was used to infuse glucose and
      AA solutions (3:1) simultaneously during the night. Eight infusions of 1000 mL m2
      of body surface area (BSA), with a 60 minute dwell time, were performed in 10
      children on peritoneal dialysis. The dialytic effluent was analyzed at every
      exchange and totaled at eight hours to evaluate volume, glucose, and AA
      concentration. Blood samples for plasma, glucose, insulin, and free AA
      determination were drawn at the beginning of automated peritoneal dialysis (APD)
      session and at each instillation of peritoneal dialysate. RESULTS: The mean
      glucose absorption was 33.7 +/- 10.0% and the AA absorption was 55.2 +/- 13.2% of
      the infused amount, and the ratio of nonprotein calorie (derived from glucose) to
      nitrogen (derived from AA) was 115.4:1. The insulin levels returned to normal
      only three hours after the beginning of APD. The free AA plasma levels were
      already increased two hours after dinner and remained high for the entire APD
      treatment because of the continuous absorption of AA from the peritoneum. The BUN
      levels did not increase despite the supply of AA. CONCLUSIONS: This APD procedure
      may improve utilization of AA for protein synthesis, as suggested by the lack of
      increase of the BUN levels with this regimen.

PMID- 11318969
TI  - Elevated plasma F2-isoprostanes in patients on long-term hemodialysis.
AB  - BACKGROUND: End-stage renal disease (ESRD) patients on long-term hemodialysis
      (HD) may be under increased oxidative stress, caused by either HD or renal
      failure. Plasma F2-isoprostanes have been established as an important indicator
      of in vivo oxidative stress. METHODS: Plasma esterified F2-isoprostanes were
      measured in 25 HD patients and 23 controls with normal renal function, employing
      gas chromatography-mass spectrometry with negative chemical ionization (GC-MS
      NCI). C-reactive protein (CRP) was determined concurrently in patients and
      controls by enzyme-linked immunosorbent assay (ELISA). alpha-Tocopherol, retinol,
      albumin and creatinine were also determined. RESULTS: The average total
      esterified F2-isoprostanes in the ESRD patients was 1.62 +/- 0.73 vs. 0.27 +/-
      0.10 ng/mL in controls (P < 0.001), with no overlap between patients and
      controls. Plasma F2-isoprostanes in diabetic ESRD patients were similar to F2
      isoprostanes in patients with other causes for renal failure. In a subset of 10
      of these ESRD patients evaluated eight months after the initial measurement,
      plasma-esterified F2-isoprostanes were not altered by an individual dialysis
      session. Average plasma CRP values were also higher in HD patients (P < 0.02),
      but some patients had CRP values that were similar to controls. In the HD
      patients, total plasma F2-isoprostanes and plasma CRP were correlated (r = 0.48,
      P = 0.015). Plasma alpha-tocopherol did not differ between patients and controls,
      but plasma retinol was higher in patients (3.15 +/- 1.71 micromol/L) than in
      controls (1.97 +/- 0.51 micromol/L, P < 0.05). CONCLUSIONS: These results are
      consistent with the hypothesis that oxidative stress in ESRD patients contributes
      to increased values of esterified plasma F2-isoprostanes, with concurrent
      increases in plasma CRP levels in some patients. Impaired clearance of esterified
      F2-isoprostanes may contribute to the elevated levels in renal failure. Plasma
      esterified F2-isoprostanes may be a useful indicator to evaluate effectiveness of
      interventions to decrease oxidative stress and associated inflammation.

PMID- 11318971
TI  - Flow in hemodialysis grafts after angioplasty: Do radiologic criteria predict
      success?
AB  - BACKGROUND: The anatomic success of percutaneous angioplasty of venous stenosis
      is determined by the improvement in cross-sectional diameter of the vessel. A
      successful outcome is defined as a residual stenosis of <30%. The purpose of this
      study was to determine whether the angiographic assessment of a venous stenosis
      correlates with the change in graft blood flow following angioplasty. METHODS:
      Twenty-two hemodialysis patients with decreased intragraft blood flow (<700
      mL/min) underwent diagnostic fistulography and angioplasty. All grafts were
      patent at the time of the procedure. Intragraft blood flow was measured before
      and after angioplasty using the ultrasonic dilution technique. Change in graft
      blood flow after angioplasty was correlated to the morphologic changes of the
      treated stenosis. RESULTS: The mean preangioplasty and postangioplasty graft
      blood flows were 457 +/- 136 and 818 +/- 202 mL/min, respectively. The mean
      degree of stenosis before angioplasty was 74 +/- 15% and 18 +/- 14% after
      dilation (P < 0.001). The only variable that significantly correlated with
      postangioplasty blood flow was preangioplasty flow (r2 = 0.22, P < 0.001). The
      postangioplasty blood flow was not significantly different than the highest
      recorded blood flow measured in that graft (798 +/- 213 mL/min, P = NS). There
      was no significant correlation between the change in blood flow and the change in
      percentage of stenosis. CONCLUSION: Following angioplasty of a venous stenosis,
      the graft blood flow is most closely predicted by the preprocedural blood flow
      and is similar to the highest recorded blood flow ever measured in that graft.
      Angiographic criteria to assess the success of angioplasty are not predictive of
      changes in blood flow.

PMID- 11318972
TI  - Childhood ADPKD: answers and more questions.

PMID- 11318973
TI  - ANCA signaling: not just a matter of respiratory burst.

PMID- 11318974
TI  - Idiopathic membranous glomerulonephritis.

PMID- 11318975
TI  - Regulation of cholangiocyte proliferation.
AB  - Intrahepatic bile duct epithelial cells (i.e., cholangiocytes) are the target
      cells of chronic cholestatic liver diseases (i.e., cholangiopathies), which makes
      these cells of great interest to clinical hepatologists. This review will focus
      on "typical" cholangiocyte proliferation, whereas "atypical" (extension of
      cholangiocyte proliferation into parenchyma), and premalignant "oval" cell
      proliferation are reviewed elsewhere. The bile duct ligated (BDL) rat model,
      where most of the known mechanisms of cholangiocyte proliferation have been
      illustrated, was the first and remains the prototype animal model for "typical"
      cholangiocyte proliferation. Following a short overview of cholangiocyte
      functions, we briefly discuss the: (i) in vivo models [i.e., BDL (Fig. 1 and 4),
      chronic alpha-naphthylisothiocyanate (ANIT) or bile acid feeding (Fig. 2), acute
      carbon tetrachloride (CCl4) feeding and partial hepatectomy; and (ii) in vitro
      experimental tools [e.g., purified cholangiocytes and isolated intrahepatic bile
      duct units (IBDU)] that are key to the understanding of the mechanisms of
      "typical" cholangiocyte growth. In the second part of the review, we discuss a
      number of potential factors or conditions [e.g., gastrointestinal hormones,
      nerves, estrogens, blood supply, and growth factors] as well as the intracellular
      mechanisms [e.g., adenosine 3',5'-monophosphate (cAMP), and protein kinase C
      (PKC)] that may regulate "typical" cholangiocyte hyperplasia.

PMID- 11318976
TI  - Cholestatic syndrome with bile duct damage and loss in renal transplant
      recipients with HCV infection.
AB  - BACKGROUND/AIMS: Bile duct cells are known to be susceptible to hepatitis B and C
      virus, while it has been recently suggested that hepatitis B virus (HBV) and
      hepatitis C virus (HCV) infection may have a direct role in the pathogenesis of
      vanishing bile duct syndrome (VBDS) after liver transplantation. We report the
      development of a cholestatic syndrome associated with bile duct damage and loss
      in four HCV-infected renal transplant recipients. METHODS: All four patients were
      followed up biochemically, serologically and with consecutive liver biopsies.
      Serum HCV RNA was quantitatively assessed and genotyping was performed. RESULTS:
      Three patients were anti-HCV negative and one was anti-HCV/HBsAg positive at the
      time of transplantation and received the combination of methylprednisolone,
      azathioprine and cyclosporine A. Two patients became anti-HCV positive 1 year and
      one patient 3 years post-transplantation. Elevation of the cholestatic enzymes
      appeared simultaneously with seroconversion, or 2-4 years later, and was related
      to lesions of the small-sized interlobular bile ducts. Early bile duct lesions
      were characterized by degenerative changes of the epithelium. Late and more
      severe bile duct damage was associated with bile duct loss. The progression of
      the cholestatic syndrome coincided with high HCV RNA serum levels, while HCV
      genotype was 1a and 1b. Two patients (one with HBV co-infection) developed
      progressive VBDS and died of liver failure 2 and 3 years after biochemical onset.
      One patient, despite developing VBDS within a 10-month period, showed marked
      improvement of liver function after cessation of immunosuppression because of
      graft loss. The fourth patient, who had mild biochemical and histological bile
      duct changes, almost normalized liver function tests after withdrawal of
      azathioprine. CONCLUSION: A progressive cholestatic syndrome due to bile duct
      damage and loss may develop in renal transplant patients with HCV infection. The
      occurrence of the lesions after the appearance of anti-HCV antibodies and the
      high HCV RNA levels are indicative of viral involvement in the pathogenesis.
      Withdrawal of immunosuppressive therapy may have a beneficial effect on the
      outcome of the disease.

PMID- 11318977
TI  - Cyclin D1 overexpression in hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: Cyclin D1 gene amplification and cyclin D1 protein
      overexpression have been reported in various human tumors, including
      hepatocellular carcinoma (HCC). However, their significance is still
      controversial. In the present study, we examined the expression of cyclin D1 and
      its relationships to p53 and Ki-67 in HCCs. METHODS: The expression and
      topological distribution of cyclin D1, p53 and Ki-67 in 50 cases of HCC were
      examined immunohistochemically, and the relationship between the expression of
      these proteins and their pathologic features was investigated. RESULTS:
      Overexpression of cyclin D1 was noted in 58% of the HCC cases, and significantly
      associated with a well-differentiated histology and a low Ki-67 labeling index
      (LI). Cyclin D1 overexpression was also observed in all (7 of 7) dysplastic
      nodules and in non-neoplastic hepatocytes. On the other hand, aberrant p53
      expression was detected in 36% of the cases, which showed positive relationships
      with poor differentiation, portal vein invasion, and KI-67 LI. Only eight of the
      50 cases examined (16%) were positive for both cyclin D1 and p53, which showed
      only a small number of cyclin D1-positive cells. There was no significant
      relationship between the expressions of cyclin D1 and p53. CONCLUSIONS: Our
      results suggest that cyclin D1 overexpression may be an early event in
      hepatocarcinogenesis and that it plays a role in tumor differentiation. In
      addition, cyclin D1 expression is not correlated with tumor cell proliferation in
      HCCs.

PMID- 11318978
TI  - Role of myofibroblasts in tumour encapsulation of hepatocellular carcinoma in
      haemochromatosis.
AB  - BACKGROUND/AIMS: Hepatocellular carcinoma is a common malignancy and a major
      complication of untreated haemochromatosis. Encapsulation of liver tumours has
      been associated with a better prognosis and longer disease-free periods following
      resection. This study investigated the source of the tumour capsule in patients
      with haemochromatosis and coexisting hepatocellular carcinoma and examined
      potential factors influencing development. METHODS: Five haemochromatosis
      patients with encapsulated hepatocellular carcinoma were studied. Myofibroblasts
      were identified using combined immunohistochemistry and in situ hybridisation for
      alpha-smooth muscle actin and procollagen alpha1(I) mRNA, respectively.
      Immunohistochemistry was also performed for transforming growth factor (TGF)
      beta1, platelet-derived growth factor (PDGF)-beta receptor and malondialdehyde.
      RESULTS: Procollagen alpha1(I) mRNA co-localised to alpha-smooth muscle actin
      positive myofibroblasts. The number of myofibroblasts was maximal within the
      capsule and decreased away from the tumour. TGF-beta1 protein was expressed in
      iron-loaded cells in non-tumour liver at the interface of tumour capsule. PDGF
      beta receptor expression was observed in mesenchymal cells in the tumour capsule
      and in portal tracts. Malondialdehyde adducts were observed in the tumour, non
      tumour tissue and in the capsule. CONCLUSIONS: This study provides evidence that
      myofibroblasts are the cell type responsible for collagen production within the
      tumour capsule surrounding hepatocellular carcinoma in haemochromatosis. The
      production of TGF-beta1 by iron-loaded hepatic cells at the tumour capsule
      interface may perpetuate the myofibroblastic phenotype, resulting in the
      formation of the tumour capsule.

PMID- 11318979
TI  - Expression of isoforms and splice variants of the latent transforming growth
      factor beta binding protein (LTBP) in cultured human liver myofibroblasts.
AB  - BACKGROUND/AIMS: The activation of hepatic stellate cells (HSC) to extracellular
      matrix (ECM) producing myofibroblasts (MFB) is the key pathogenetic event in
      human liver fibrogenesis. Latent transforming growth factor beta binding protein
      (LTBP), a component of the profibrogenic large latent transforming growth factor
      (TGF)-beta complex, is suggested to be important for secretion, latency, storage
      and activation of TGF-beta in the ECM. This study was performed to identify the
      expression profile of all hitherto known LTBP isoforms and LTBP splice variants
      in conjunction with that of TGF-beta isoforms in cultured human liver MFB.
      METHODS: Cultured human MFB were analyzed for TGF-beta and LTBP using reverse
      transcription polymerase chain reaction (RT-PCR), sequence analysis,
      immunofluorescence staining, metabolic labeling, immunoprecipitation, and enzyme
      linked immunosorbent assay (ELISA). RESULTS: Transcripts of all three TGF-beta
      isoforms, of all four LTBP isoforms and of nearly all splice variants of LTBP-1
      and LTBP-4 so far known were detected. Metabolic labeling followed by
      immunoprecipitation with anti-LTBP-1 antibody revealed the synthesis of LTBP
      proteins. Secretion of free LTBP and LTBP integrated into the large latent TGF
      beta complex was demonstrated by size-exclusion chromatography. Co-localization
      of LTBP-1 and -2 with fibronectin and collagen type I was observed by double
      immunofluorescence staining. CONCLUSION: The expression of a complete profile of
      hitherto known LTBP proteins by cultured human MFB suggests a role in modulating
      the bioactivity of TGF-beta in the diseased liver.

PMID- 11318980
TI  - Enhanced expression of endothelin receptor subtypes in cirrhotic rat liver.
AB  - BACKGROUND/AIMS: A number of vasoactive substances have been implicated as
      potential mediators of intrahepatic portal hypertension. Endothelin (ET)-1 has
      been suggested to be involved in the regulation of hepatic microcirculation and
      development of portal hypertension. The aim of this study was to clarify the
      localization of two subtypes of ET receptors, ET A (ETAR) and B receptors (ETBR),
      in normal rat liver, and how the receptor expressions are altered in CCl4-induced
      cirrhotic rat liver. METHODS: Liver specimens were examined immunohistochemically
      after reacting with anti-ETAR and anti-ETBR rabbit polyclonal antibodies.
      Immunogold staining was also performed using the same antibodies, and examined
      under light and electron microscopy. RESULTS: In normal rat liver,
      immunohistochemistry revealed expression of ETAR and ETBR on the hepatic
      sinusoidal lining cells. By immunogold electron microscopy, electron-dense gold
      particles indicating the presence of ETARs were localized mainly on hepatic
      stellate cells (HSCs) and to a lesser extent on sinusoidal endothelial cells
      (SECs), while ETBRs were expressed equally intensely on HSCs and SECs. In
      cirrhotic animals, both ETAR and ETBR increased significantly on HSCs, while
      there were no significant increases in either receptor on SECs. CONCLUSIONS: In
      the normal state, HSCs possess both ETARs and ETBRs, while SECs mainly possess
      ETBRs. In cirrhosis, endothelins may exert more intense effects on HSCs via the
      enhanced ETARs and ETBRs, causing an increase in hepatic sinusoidal microvascular
      tone.

PMID- 11318981
TI  - Circulating levels of insulin-like growth factors and their binding proteins in
      patients with chronic liver disease: lack of correlation with bone mineral
      density.
AB  - BACKGROUND/AIMS: Insulin-like growth factor-I (IGF-I) levels are low in patients
      with chronic liver disease (CLD) and have been found to correlate with
      measurements of bone mineral density (BMD) in men with viral cirrhosis. The aim
      of this study was to investigate the relationship between circulating IGF-I
      levels and BMD in patients with CLD of other causes. METHODS: Fifty-eight
      patients with CLD were included. Age- and sex-matched normal individuals served
      as controls. Serum levels of IGF-I and IGF-II and their binding proteins (IGFBP-1
      3) were measured by radioimmunoassay. BMD was measured by dual energy X-ray
      absorptiometry. RESULTS: IGF-I levels were 57+/-33 and 136+/-48 ng/ml; p<0.0001
      in patients and controls, respectively. IGF-II and IGFBP-3 levels were lower
      (p<0.0001) and IGFBP-1 and IGFBP-2 levels were higher in patients compared with
      controls (p<0.0005 and p<0.0001, respectively). All growth factors, except for
      IGFBP-2, correlated with parameters of liver function. In a multiple regression
      analysis, adjusting for age, no correlation was found between IGF-I, IGF-II,
      IGFBP-1-3 and BMD in either patients or controls. CONCLUSION: Patients with CLD
      have low levels of IGF-I, IGF-II and IGFBP-3 that correlate with liver function.
      No relationship was found between low levels of growth factors and BMD.

PMID- 11318982
TI  - Colchicine for alcoholic and non-alcoholic liver fibrosis or cirrhosis.
AB  - AIMS/BACKGROUND: Colchicine is an anti-inflammatory and anti-fibrotic drug.
      Several randomized clinical trials have addressed the question whether colchicine
      has any efficacy in patients with alcoholic as well as non-alcoholic fibrosis and
      cirrhosis. The objectives were to assess the efficacy of colchicine evaluated in
      randomized trials on mortality, liver related mortality, liver related
      complications, liver fibrosis markers, liver histology, alcohol consumption,
      quality of life, and health economics in patients with alcoholic and non
      alcoholic fibrosis or cirrhosis. METHODS: Interventions encompassed peroral
      colchicine at any dose versus placebo or no intervention. The trials could be
      double-blind, single-blind or unblinded. The trials could be unpublished or
      published as an article, an abstract, or a letter, and no language limitations
      were applied. All analyses were performed according to the intention-to-treat
      METHOD: MEDLINE, The Cochrane Controlled Trials Register, The Cochrane Hepato
      Biliary Group Controlled Trials Register and full text searches were combined.
      RESULTS: Combining the results of 14 randomized clinical trials including 1138
      patients demonstrated no significant effects of colchicine on mortality (odds
      ratio (OR): 0.91; 95% confidence interval (CI) 0.64, 1.31), liver related
      mortality (OR: 0.98; CI 0.56, 1.74), complications (OR: 1.06; CI 0.65, 1.73), and
      the other outcomes. Colchicine was associated with a significantly increased risk
      of adverse events (OR: 4.41; CI 2.24, 8.70; p< 0.001). CONCLUSIONS: Colchicine
      should not be used for liver fibrosis or liver cirrhosis irrespective of
      etiology. Future trials on colchicine for liver diseases ought to be large.

PMID- 11318983
TI  - Hepatitis C virus core protein promotes cell proliferation through the
      upregulation of cyclin E expression levels.
AB  - AIMS/BACKGROUND: The hepatitis C virus (HCV) core protein is known to play an
      important role in hepatocarcinogenesis. Recent studies have suggested that the
      increased proliferation rate of hepatocytes is a major risk factor for the
      development of hepatocellular carcinoma. In this study, we investigated whether
      the HCV core protein promotes the cell growth rate through the modulation of
      cyclin E expression levels. METHODS/RESULTS: HCV core stable transfectant Rat-1
      cell lines showed a markedly increased proliferation rate compared to mock cells.
      Cyclin E expression and its associated kinase activities were remarkably
      increased in HCV core stable transfectants. Cyclin E mRNA levels were also
      upregulated in these cell lines. CONCLUSIONS: Our data suggest that the HCV core
      protein promotes cell proliferation through upregulation of the cyclin E
      expression levels, implying this property of HCV core protein plays an important
      role in hepatocarcinogenesis.

PMID- 11318984
TI  - HLA class II alleles in Chinese patients with hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: Recent reports of an association between human leucocyte
      antigens (HLA) and persistence of hepatitis B virus infection, and the familial
      clustering of hepatocellular carcinoma raise the question of genetic
      susceptibility. Previous studies have been limited to serological phenotyping of
      HLA B and DR antigens. The aim of this study was to use molecular genotyping to
      investigate HLA class II as a risk factor for the development of hepatocellular
      carcinoma in Hong Kong Chinese. METHODS: We determined HLA DRB1, DQA1, DQB1 and
      DPB1 alleles in 123 hepatitis B surface antigen positive patients (84 with
      hepatocellular carcinoma and 39 without) and 124 matched controls. RESULTS: The
      alleles DRB1*1501 (36% of HCC patients versus 19% of controls, odds ratio=2.44),
      DQA1*0102 (42% versus 26%, odds ratio=2.07), and DPB1*0501 (80% versus 63%, odds
      ratio=2.35) were significantly more common in patients with hepatocellular
      carcinoma, and DQA1*03 (36% versus 56%, odds ratio=0.53), DQB1*0302 (4.% versus
      13%, odds ratio=0.25) and DPB1*0201 (14% versus 29%, odds ratio=0.4) were found
      at significantly lower frequencies. CONCLUSIONS: Although none of these
      associations was significant after correction for multiple testing, this report
      suggests that further investigations are warranted.

PMID- 11318985
TI  - Overexpressed growth hormone (GH) synergistically promotes carcinogen-initiated
      liver tumour growth by promoting cellular proliferation in emerging
      hepatocellular neoplasms in female and male GH-transgenic mice.
AB  - BACKGROUND/AIMS: Growth hormone (GH), when overexpressed in male and female GH
      transgenic mice, is known to induce liver tumours within 1 year. This study aimed
      to gain a clearer understanding of the interaction between GH and tumour cells in
      vivo. METHODS/RESULTS: The carcinogen diethylnitrosomine (DEN) was administered
      to neo-natal transgenic and non-transgenic mice maintained in a
      "hepatocarcinogenesis resistant" genetic background (C57BL/6J). Macroscopic,
      microscopic and liver weight/body weight ratio analyses revealed that carcinogen
      induced hepatocarcinogenesis was dramatically accelerated in young GH-transgenic
      mice compared to non-transgenic counterparts. Image analysis of microscopic
      hepatocellular neoplasms showed rapidly increasing tumour burdens, and neoplastic
      foci size over time in young adult GH-transgenic mice. The magnitude of enhanced
      tumour growth was equivalent in both male and female transgenic mice, whereas
      much lower and sexually dimorphic tumour growth rates (males>females) were
      observed in non-transgenic mice treated with DEN. BrdU labelling experiments
      demonstrated that rapid tumour growth in carcinogen-treated GH-transgenic mice
      was due to the promotion of cell proliferation in emerging lesions. Tumour cell
      proliferation in young GH-transgenic mice was 2.6- and 4-fold higher,
      respectively, than that observed in similar age male and female non-transgenic
      mice. Interestingly, both GH-transgenic and non-transgenic mice displayed
      progressively slower tumour growth rates in older animals. CONCLUSION: Overall,
      GH synergistically promotes carcinogen-induced hepatocarcinogenesis in both sexes
      of GH-transgenic mice by stimulating tumour cell proliferation.

PMID- 11318986
TI  - Severe hypercalcemia and solitary hepatic mass as initial manifestation of
      primary hepatic lymphoma.

PMID- 11318988
TI  - Assessment: the gap between theory and practice.

PMID- 11318989
TI  - Serendipity -- yet another nail in the coffin.

PMID- 11318990
TI  - Community-based education: is the effort worth it?

PMID- 11318991
TI  - Assessing the assessors' assessment.

PMID- 11318992
TI  - Mind the gap: some reasons why medical education research is different from
      health services research.

PMID- 11318993
TI  - Standardized or real patients to test clinical competence? The long case
      revisited.
AB  - BACKGROUND: In undergraduate clinical examinations, the use of real patients as
      long cases is being replaced by objective structured clinical examinations
      (OSCEs) which use simulated scenarios, although we lack published psychometric
      data on long cases to support the move from real to simulated patients. AIM: To
      assess candidate performance across two history-taking long cases to estimate the
      number of cases required for a reliable assessment. Results are compared with
      psychometric data from an OSCE. SETTING: A final-year qualifying undergraduate
      clinical examination. METHOD: Two observed history-taking long cases were
      included, alongside an OSCE. Candidates interviewed two unstandardized real
      patients. The history-taking part (14 minutes) was observed, uninterrupted, by
      examiner(s) who assessed data gathering, interviewing, and diagnostic and
      management skills. The presentation (7 minutes) was unstructured; the examiner(s)
      intervened as appropriate. Marks were expressed as a percentage of the total
      possible score and analysed using generalizability theory to estimate intercase
      reliability. RESULTS: Two examiner pairs independently rated both long cases for
      79 (36.7%) of the 214 candidates. Projections based on generalizability theory
      showed that 10 20-minute cases would give reliabilities of 0.84 for single-marked
      and 0.88 for double-marked candidates, compared with a projected reliability of
      0.73 for the same 214 candidates taking the OSCE. CONCLUSION: If history-taking
      long cases are observed, three-and-a-half hours of testing time using 10
      unstandardized patients would produce a reliable test. Long cases therefore are,
      in terms of reliability, no worse and no better than OSCEs in assessing clinical
      competence.

PMID- 11318994
TI  - Composite undergraduate clinical examinations: how should the components be
      combined to maximize reliability?
AB  - BACKGROUND: Clinical examinations increasingly consist of composite tests to
      assess all aspects of the curriculum recommended by the General Medical Council.
      SETTING: A final undergraduate medical school examination for 214 students. AIM:
      To estimate the overall reliability of a composite examination, the correlations
      between the tests, and the effect of differences in test length, number of items
      and weighting of the results on the reliability. METHOD: The examination
      consisted of four written and two clinical tests: multiple-choice questions (MCQ)
      test, extended matching questions (EMQ), short-answer questions (SAQ), essays, an
      objective structured clinical examination (OSCE) and history-taking long cases.
      Multivariate generalizability theory was used to estimate the composite
      reliability of the examination and the effects of item weighting and test length.
      RESULTS: The composite reliability of the examination was 0.77, if all tests
      contributed equally. Correlations between examination components varied,
      suggesting that different theoretically interpretable parameters of competence
      were being tested. Weighting tests according to items per test or total test time
      gave improved reliabilities of 0.93 and 0.81, respectively. Double weighting of
      the clinical component marginally affected the reliability (0.76). CONCLUSION:
      This composite final examination achieved an overall reliability sufficient for
      high-stakes decisions on student clinical competence. However, examination
      structure must be carefully planned and results combined with caution. Weighting
      according to number of items or test length significantly affected reliability.
      The components testing different aspects of knowledge and clinical skills must be
      carefully balanced to ensure both content validity and parity between items and
      test length.

PMID- 11318995
TI  - An outcomes research perspective on medical education: the predominance of
      trainee assessment and satisfaction.
AB  - CONTEXT: A fundamental premise of medical education is that faculty should
      educate trainees, that is, students and residents, to provide high quality
      patient care. Yet, there is little research on the effect of medical education on
      patient outcomes. OBJECTIVE: A content analysis of leading medical education
      journals was performed to determine the primary foci of medical education
      research, using a three- dimensional outcomes research framework based on the
      paradigm of health services outcomes research. DATA SOURCES: All articles in
      three medical education journals (Academic Medicine, Medical Education, and
      Teaching and Learning in Medicine) from 1996 to 1998 were reviewed. Papers
      presented at the Research in Medical Education conference at the Association of
      American Medical Colleges annual meeting during the same period, and published as
      Academic Medicine supplements, were also analysed. STUDY SELECTION: Only data
      driven articles were selected for analysis; thus editorials and abstracts were
      excluded. DATA EXTRACTION: Each article was categorized according to primary
      participant (i.e. trainee, faculty, provider and patient), outcome (performance,
      satisfaction, professionalism and cost), and level of analysis (geographic,
      system, institution and individual(s)). DATA SYNTHESIS: A total of 599 articles
      were analysed. Trainees were the most frequent participants studied (68.9%),
      followed by faculty (19.4%), providers (8.1%) and patients (3.5%). Performance
      was the most common outcome measured (49.4%), followed by satisfaction (34.1%).
      Cost was the focus of only 2.3% of articles and patient outcomes accounted for
      only 0.7% of articles. CONCLUSIONS: Medical education research is dominated by
      assessment of trainee performance followed by trainee satisfaction. Leading
      journals in medical education contain little information concerning the cost and
      products of medical education, that is, provider performance and patient
      outcomes. The study of these medical education outcomes represents an important
      challenge to medical education researchers.

PMID- 11318996
TI  - Loss of British-trained doctors from the medical workforce in Great Britain.
AB  - OBJECTIVE: To summarize trends over time in the percentage of British medical
      graduates who subsequently practise in Great Britain in the National Health
      Service (NHS), in Great Britain outside the NHS, outside Great Britain, or do not
      practise medicine. DESIGN: Questionnaire-based postal surveys and government
      employment records. SETTING: Great Britain. SUBJECTS: All British medical
      graduates of 1974, 1977, 1983, 1988, and 1993. MAIN OUTCOME MEASURES: Type and
      location of employment at successive years after graduation. RESULTS: Differences
      in career destination between cohorts were generally small. Combining data from
      all cohorts studied, 85% of doctors were working in the NHS 2 years after
      graduation, 82% after 5 and 10 years, 81% after 15 years, and 77% after 20 years.
      Part-time working was much higher among women than among men. Allowing for loss
      and part-time working, the whole-time equivalent available to the NHS at 15 years
      after graduation was 60% of women and 80% of men. More men than women worked in
      medicine outside the NHS in Britain and abroad. Loss from medicine altogether was
      small, and higher among women. CONCLUSIONS: Medical workforce planning in Great
      Britain should assume that 15-20% of home-trained doctors will not be working in
      the NHS within a few years of graduation. Comparing cohorts at the same career
      stage showed no evidence of increased loss from the NHS in recent times. Although
      a higher percentage of women than men were not working in medicine at all, recent
      trends suggest that this percentage is falling.

PMID- 11318997
TI  - Assessment dispersion matrices.

PMID- 11318998
TI  - Do short cases elicit different thinking processes than factual knowledge
      questions do?
AB  - PURPOSE: To assess whether case-based questions elicit different thinking
      processes from factual knowledge-based questions. METHOD: 20 general
      practitioners (GPs) and 20 students solved case-based questions and matched
      factual knowledge-based questions while thinking aloud. Verbatim protocols were
      analysed. Five indicators were defined: extent of protocols; immediate responses;
      re-reading of information given in the stem or case after the question had been
      read; order of re-reading information, and type of consideration, i.e. 'true
      false' type or 'vector', that is, a deliberation which has a magnitude and a
      direction. RESULTS: Cases elicited longer protocols than factual knowledge
      questions. Students re-read more given information than GPs. GPs gave an
      immediate response on twice as many occasions as students. GPs re-ordered the
      case information, whereas students re-read the information in the order it was
      presented. This ordering difference was not found in the factual knowledge
      questions. Factual knowledge questions mainly led to 'true-false' considerations,
      whereas cases elicited mainly 'vector' considerations. CONCLUSION: Short case
      based questions lead to thinking processes which represent problem-solving
      ability better than those elicited by factual knowledge questions.

PMID- 11318999
TI  - Audit and summative assessment: a completed audit cycle.
AB  - OBJECTIVE: To develop and test a system for delivering a completed audit cycle
      for summative assessment of general practitioner registrars in the United
      Kingdom. DESIGN: A trainer-based questionnaire on criteria for a completed audit
      cycle, followed by two marking exercises of audit projects submitted by general
      practice registrars. SETTING: Training practices in the West of Scotland between
      1997 and 1998. SUBJECTS: Trainers and registrars in the above practices. RESULTS:
      116 (89%) agreed that two collections of data were an essential or desirable part
      of an audit project. All 57 registrars who started in August 1997 successfully
      completed an audit cycle, seven (12%) after resubmission. Using two rather than
      three independent assessors to screen the projects, the marking instrument was
      shown to have a sensitivity of 95% (95% confidence interval (CI) +/-3.9%) and a
      specificity of 77% (95% CI +/-7.5%). All assessors found the new system easier to
      mark and 47 registrars (87%) found completing an audit cycle as or easier than
      expected. CONCLUSION: Evidence from the pilot project has shown that a general
      practice registrar's ability to review and critically analyse a piece of his/her
      work, with appropriate management of any necessary change, can be tested feasibly
      by means of a completed audit cycle within the registrar year. The process
      retains adequate levels of sensitivity and specificity and requires fewer
      assessors for marking the projects.

PMID- 11319000
TI  - Clinical assessment of dental students: values and practices of teachers in
      restorative dentistry.
AB  - OBJECTIVES: To investigate the values and practices of assessment of the clinical
      practice of dental students by a sample of teachers in restorative dentistry.
      DESIGN: A questionnaire, based on the above objectives, was designed, piloted and
      redesigned. Its content was based on evidence-based good practice in assessment.
      Structured items in the questionnaire required responses on (i) frequency of use
      and (ii) estimates of value of various approaches and characteristics of the
      assessment systems that respondents were using. SETTING: The 14 undergraduate
      dental schools of the United Kingdom. SUBJECTS: Full-time clinical teachers of
      restorative dentistry in adults (comprising conservation (including endodontics),
      periodontology and prosthodontics). RESULTS: A total of 153 usable questionnaires
      were returned (response rate 70.8%), and 38 statistically significant differences
      were reported (of which 35 were very highly significant), based on the correlated
      t statistic. Values were in line with evidence-based good practice, but practices
      were not in line with values. Particularly noteworthy were the high values
      attached to objective structured clinical examinations, self- and peer
      assessment, portfolio-based learning, feedback to students, the use of objective
      criteria, communication skills and oral health education. The corresponding
      frequency of usage of these aspects was relatively low. The reported aims of
      courses in restorative dentistry were not matched by the profile of assessment
      practices. CONCLUSIONS: The findings have implications for the development of
      student learning, assessment procedures and the management of quality and
      enhancement of dental programmes. Although this is a report of only one study, it
      relates to the major clinical component of undergraduate programmes in dentistry.
      The findings imply that the time is ripe for a reappraisal of approaches to the
      assessment of clinical competence in dentistry.

PMID- 11319001
TI  - The impact of formal instruction in clinical examination skills on medical
      student performance -- the example of peripheral nervous system examination.
AB  - BACKGROUND: Peripheral nervous system examination is an essential part of the
      full medical clerking of a patient. We have investigated the effectiveness of
      formal instruction in peripheral nervous system examination compared to the
      traditional bedside ward teaching that our students usually receive. METHOD: We
      instructed an unselected group of 22 medical students in peripheral nervous
      system examination in a clinical skills centre and evaluated them with a 12 item
      marking schedule before and after instruction. The performance of this group was
      then compared to the rest of their year (220 students) in an end of year OSCE,
      which included a neurology station assessing sensory examination of the lower
      limbs. RESULTS: Students formally instructed in neurology significantly improved
      their scores after instruction and scored 15% higher marks (90% vs. 75%) than the
      rest of their year in the end of year neurology OSCE station 2 months later (P <
      0.01, Mann Whitney U-test). They did not perform significantly better in the OSCE
      overall. CONCLUSIONS: Formal instruction in neurological examination resulted in
      a significant increase in the end of year neurology OSCE station score compared
      to traditional heterogeneous teaching methods.

PMID- 11319002
TI  - Predictability of medical students' performance at the Aga Khan University from
      admission test scores, interview ratings and systems of education.
AB  - INTRODUCTION: Performance in an admission test and carefully conducted,
      structured interview provides a uniform basis for the assessment of applicants
      prepared in different systems of education for admission to an institute of
      higher professional learning. We studied the predictability of the system of
      education followed by the students prior to entrance into the Medical College,
      the admission test scores, and interview ratings on performance after five
      trimesters at the Aga Khan University Medical College. METHOD: A cohort of 374
      medical students who were admitted during 1989--1994, were considered. The
      associations between the admission test score, interview ratings, system of
      education, and the scores obtained for anatomy, physiology, biochemistry and
      community health sciences examinations held after five trimesters were analysed
      using appropriate statistical procedures. RESULTS: Interview ratings were
      associated with the scores in Physiology but not other subjects. The chief
      finding of this study was the association between the system of education and
      performance in both the admission test and the examination after five trimesters.
      Students who followed the British school curricula for 13 years scored
      significantly higher than those who followed the 12 years of the Pakistani
      system. When controlled for the admission test score, the difference in mean
      scores of the two groups was still evident for two subjects; community health
      sciences and physiology. CONCLUSION: We believe that the evidence indicates
      differences in learning methods inculcated by the system of education prior to
      entry into the Medical College, notwithstanding the 1-year difference in duration
      of education.

PMID- 11319003
TI  - The attitudes of 'tomorrow's doctors' towards mental illness and psychiatry:
      changes during the final undergraduate year.
AB  - AIMS: To compare the efficacy of two teaching styles, didactic teaching and
      problem based learning, in producing enduring change in final-year medical
      students' attitudes towards psychiatry and mental illness. METHOD: A 1-year
      follow-up questionnaire survey of two groups of medical students taught
      psychiatry in their fourth-year training by two different methods. One-year
      follow-up scores were compared with pre-attachment and post-attachment scores in
      the fourth year. RESULTS: 70 (68%) students completed both questionnaires at
      follow-up. The follow-up scores were significantly lower compared with both the
      fourth-year pre-attachment and post-attachment scores, suggesting that the
      positive change in attitudes following psychiatric training in the fourth year
      significantly decayed during the final year. The two teaching methods did not
      differ in the magnitude of this reduction. CONCLUSIONS: The positive change that
      occurs in medical students' attitude towards psychiatry, psychiatrists and mental
      illness after their fourth-year psychiatric training is transient and decays over
      the final year.

PMID- 11319004
TI  - An inter-university community child health clinical placement programme for
      medical students.
AB  - BACKGROUND: Inpatient teaching no longer reflects the full spectrum of paediatric
      practice and community-based programmes with clearly defined aims and evaluation
      of learning are becoming increasingly important. Competition for community
      resources poses threats to the delivery of effective community child health
      learning programmes by individual medical schools. OBJECTIVES: To develop and
      evaluate a combined inter-university, child-focused, active learning programme in
      community child health. METHODS: A total of 55 postgraduate-entry medical
      students from the Flinders University of South Australia and 97 undergraduate
      entry University of Adelaide students were placed with 25 community child health
      agencies and instructed to assess services from a client perspective by tracking
      one child and family through multiple agency contacts. Following each placement,
      achievement of specific programme aims was evaluated by students and agency staff
      using a 7-point Likert scale. RESULTS: Students and agency staff indicated
      substantial achievement of programme aims. Mean agency ratings were significantly
      higher than student ratings for three aims: students' experiencing a wider
      spectrum of health care problems than in teaching hospitals (5.7 +/- 1.5 versus
      4.9 +/- 1.6, P < 0.001); the importance of social and environmental factors (5.9
      +/- 1.0 versus 5.2 +/- 1.4, P < 0.001), and the importance of coordinating care
      (6.0 +/- 1.0 versus 5.2 +/- 1.2, P < 0.001). Ratings from undergraduate-entry
      students differed from those of postgraduate-entry students only with respect to
      the importance of social and environmental factors (4.8 +/- 1.4 versus 5.7 +/-
      1.1, P < 0.001). CONCLUSIONS: The new collaborative Community Child Health
      Programme substantially achieved learning aims and demonstrated effective
      integration of postgraduate- and undergraduate-entry medical students from two
      universities.

PMID- 11319005
TI  - Does community-based experience alter career preference? New evidence from a
      prospective longitudinal cohort study of undergraduate medical students.
AB  - CONTEXT: Previous studies have shown that most medical students want a hospital
      based career, but the protagonists of community-based teaching predict that
      increased community exposure within undergraduate curricula will alter subsequent
      career preferences. OBJECTIVES: To evaluate the impact on career preference and
      other attitudes of a year with substantial community exposure, compared with a
      year of hospital-based learning. DESIGN: Questionnaire to student cohort before
      and after two consecutive levels of the course, one with, and the other prior to,
      substantial community placement. SETTING: Sheffield Medical School. SUBJECTS:
      Total of 260 students in the third and fourth year of the MBChB degree. RESULTS:
      There were significant differences in career preference and attitude to primary
      care after the year with a community placement, with more students expressing a
      preference for a community-based career. This was particularly true for women,
      and less true for non-European students. Conversely, the hospital-based students,
      especially men, showed a significant change toward hospital-based careers.
      CONCLUSION: The findings support the hypothetical advantages of shifting medical
      education to primary care settings, both in encouraging a career in general
      practice and in the retention of appropriate professional attitudes.

PMID- 11319006
TI  - Designing a community-based fourth-year obstetrics and gynaecology module: an
      example of innovative curriculum development.
AB  - INTRODUCTION: This paper describes the design and evaluation of the community
      based obstetrics and gynaecology module at St Bartholomew's and the Royal London
      School of Medicine and Dentistry. This module sets out to comply with the General
      Medical Council's recommendations of encouraging students to consider the
      community perspective, and places less emphasis on a disease-orientated approach.
      OBJECTIVES: The development of the module, issues of improving student acceptance
      of the course, staff development and the benefits of community teaching in
      obstetrics and gynaecology are discussed. MODULE ORGANIZATION: The 2-week module
      precedes the 8-week hospital obstetrics and gynaecology firms that occur in the
      fourth undergraduate year. The course is organized into three components: general
      practice, departmental teaching, and self-directed learning. Students are
      allocated to general practices for their clinical teaching, for eight sessions.
      Seven departmental sessions are run by the Academic Department of General
      Practice and Primary Care. These include a review of the students' self-directed
      learning. EVALUATION AND CONCLUSION: Evaluation data are reported for the three
      components of the course. Overall the majority of students rated the module as
      useful, GP attachments being most favourably received. The majority of students
      have grasped the basic obstetric and gynaecological history and examination
      skills and found this useful before starting their hospital firms. Aspects of a
      specialist subject, such as, obstetrics and gynaecology, can be taught
      successfully in the community and GP tutors are, as yet, an untapped source of
      excellent obstetric and gynaecology teaching.

PMID- 11319007
TI  - Historical analysis: a new approach comparing publications from inside and
      outside the discipline over time.
AB  - One new way of analysing a discipline is to track the major ideas it produces
      over time (outputs). This can also be done with the texts which the discipline
      acknowledges through citations (inputs). Using the criteria of citations in peer
      reviewed journals and frequency of citation, it is possible to chart trends and
      even make predictions. A table for the discipline of general practice over 150
      years is shown. This historical analysis suggests that the discipline of general
      practice was essentially clinical and primarily concerned with physical illness
      until 1965 and has since then been more concerned with psychosocial factors.

PMID- 11319008
TI  - Recent perspectives on clinical teaching.
AB  - Clinical teaching is part of a doctor's professional life, whether it takes place
      in surgeries, clinics or in hospitals, with undergraduates, postgraduate trainees
      or colleagues. Learning to teach well means questioning the effectiveness of some
      of the old teaching methods, exploring new ideas and trying out new methods in
      different situations. It means collaborating more closely with colleagues and
      learners about developing and implementing new approaches to medical education.
      This paper is the first of an occasional series of articles about the practical
      aspects of clinical teaching. The articles have the following characteristics:
      they explore contemporary themes in medical and health care education; they use
      up-to-date references; they are a quick and easy resource for busy teachers; they
      explore new ideas about teaching and learning, and they provide a reference list
      of relevant papers. This article deals with recent ideas about clinical teachers'
      knowledge and roles, teaching and organizational strategies, and the measurement
      of teaching effectiveness.

PMID- 11319009
TI  - Singlet oxygen imaging in Arabidopsis thaliana leaves under photoinhibition by
      excess photosynthetically active radiation.
AB  - Arabidopsis thaliana leaves were infiltrated with DanePy (3-(N-diethylaminoethyl)
      N-dansyl)aminomethyl-2,5-dihydro-2,2,5,5-tetramethyl-1H-pyrrole), a double,
      fluorescent and spin sensor of singlet oxygen. DanePy fluorescence was imaged by
      laser scanning microscopy. We found that DanePy penetrated into chloroplasts but
      did not alter the functioning of the photosynthetic electron transport as
      assessed by chlorophyll fluorescence induction. In imaging, DanePy fluorescence
      was well distinct from chlorophyll fluorescence. Photoinhibition by excess
      photosynthetically active radiation caused quenching of DanePy fluorescence in
      the chloroplasts but not in other cell compartments. When leaves were infiltrated
      with dansyl, the fluorescent group in DanePy, there was no fluorescence quenching
      during photoinhibition. This shows that the fluorescence quenching of DanePy is
      caused by the conversion of its pyrrol group into nitroxide, i.e. it was caused
      by the reaction of singlet oxygen with the double sensor and not by artifacts.
      These data provide direct experimental evidence for the localization of singlet
      oxygen production to chloroplasts in vivo.

PMID- 11319010
TI  - Rice alpha-mannosidase digesting the high mannose glycopeptide of glutelin.
AB  - alpha-Mannosidase (EC 3.2.1.24) from rice dry seeds was purified to homogeneity.
      Optimum pH and Km for pNP-alpha-Man hydrolysis were pH 4.3-4.5 and 1.04 mM,
      respectively. The enzyme digested mannobioses such as Manalpha-1,2Man, Manalpha
      1,6Man, Manalpha-1,3Man but Manalpha-1,4Man. Zn2+ ion was required for the
      activity, whereas EDTA and swainsonine inhibited the activity by 80 and 96%,
      respectively. The rice storage protein, glutelin was prepared and its basic
      subunits were shown to have high mannose-type sugar chains by two-dimensional
      mapping using NH2-P and C18 silica columns. They were Man9GlcNAc2, Man8GlcNAc2,
      Man7GlcNAc2, Man6GlcNAc2 and Man5GlcNAc2. All these oligosaccharides were
      digested by the purified alpha-mannosidase, and Man-GlcNAc2 and mannose were
      formed. Glycopeptides, having these high mannose-type sugar chains, could also be
      digested by the alpha-mannosidase. Subunits were prepared from glutelin basic
      subunit and the richest subunit among them, subunit 2 (isoform 2), was digested
      by the alpha-mannosidase. Isoform 2 was digested by V8 protease only partially
      and slowly. However, isoform 2, pre-treated with the alpha-mannosidase, was
      rapidly and completely digested by V8 protease.

PMID- 11319011
TI  - Production of clover broomrape seed germination stimulants by red clover root
      requires nitrate but is inhibited by phosphate and ammonium.
AB  - The effect of nutrients (nitrate, ammonium, urea, phosphate and potassium) on the
      production and/or exudation of germination stimulants for clover broomrape
      (Orobanche minor Sm.), a root holoparasite, by its host red clover (Trifolium
      pratense L.) was examined using hydroponically grown material. Potassium (K2SO4)
      concentrations up to 100 mg l-1 (based on K) did not affect the production of
      germination stimulants by red clover while, in contrast, phosphate (NaH2PO4) was
      highly inhibitory even at concentrations as low as 1 mg l-1 (based on P). Nitrate
      (NaNO3) markedly promoted stimulant production in a dose-dependent manner from 2
      to 50 mg l-1 (based on N). Ammonium [(NH4)2SO4] had no effect at 2 mg l-1 (based
      on N) but was inhibitory at higher concentrations. Ammonium is known to be a seed
      germination inhibitor of root parasites, indicating that ammonium has a dual
      inhibitory action. Urea had no effect at 2 mg l-1 (based on N) but was promotive
      at higher concentrations. These results provide a basis for the inhibitory
      effects of nitrogen fertilizer on infection by root parasitic weeds, broomrapes
      and witchweeds, and explain why these parasites prevail in areas where there is
      lower phosphorus availability in soils.

PMID- 11319012
TI  - Changes induced by Fe deficiency and Fe resupply in the organic acid metabolism
      of sugar beet (Beta vulgaris) leaves.
AB  - The effects of iron deficiency and iron resupply on the metabolism of leaf
      organic acids have been investigated in hydroponically grown sugar beet. Organic
      acid concentrations and activities in leaf extracts of several enzymes related to
      organic acid metabolism were measured. Enzymes assayed included phosphoenol
      pyruvate carboxylase (PEPC; EC 4.1.1.31), different Krebs cycle enzymes: malate
      dehydrogenase (MDH; EC 1.1.1.37), aconitase (EC 4.2.1.3), fumarase (EC 4.2.1.2),
      citrate synthase (CS; EC 4.1.3.7) and isocitrate dehydrogenase (ICDH; EC
      1.1.1.42), glucose-6-phosphate dehydrogenase (G6PDH; EC 1.1.1.49) and two enzymes
      related to anaerobic metabolism (lactate dehydrogenase [LDH]; EC 1.1.1.27, and
      pyruvate decarboxylase [PDC]; EC 4.1.1.1). Iron concentration in leaves was
      severely decreased by iron deficiency. Iron resupply caused an increase in iron
      concentrations, reaching levels similar to the controls in 96 h. Iron deficiency
      induced a 2.3-fold (from 16 to 37 mmol m-2) increase in leaf total organic acid
      concentration. Organic anion concentrations were still 4-fold higher than the
      controls 24 h after resupply and decreased to values similar to those found in
      the controls after 96 h. All measured enzymes had increased activities in
      extracts of iron-deficient leaves when compared to the controls and generally
      decreased to control values 24 h after iron addition. These data provide evidence
      that organic acid accumulation in iron-deficient leaves is likely not due to an
      enhancement in leaf carbon fixation. Instead, this accumulation could be
      associated with organic acid export from the roots to the leaves via xylem.

PMID- 11319013
TI  - Antioxidative enzymes in seedlings of Nelumbo nucifera germinated under water.
AB  - Dry seeds of anoxia-tolerant lotus (Nelumbo nucifera Gaertn=Nelumbium speciosum
      Willd.) have green shoots with plastids containing chlorophyll, so photosynthesis
      starts even in seedlings germinated under water, namely hypoxia. Here we
      investigated antioxidative enzyme changes in N. nucifera seedlings responding to
      oxygen deficiency. The activity of superoxide dismutase (SOD; EC 1.15.1.1),
      dehydroascorbate reductase (DHAR; EC 1.8.5.1) and glutathione reductase (GR; EC
      1.6.4.2) were lower in seedlings germinated under water (submerged condition) in
      darkness (SD seedlings) than those found in seedlings germinated in air and
      darkness (AD seedlings). In contrast, ascorbate peroxidase (APX; EC 1.11.1.11)
      activity was higher in SD seedlings and the activity of catalase (EC 1.11.1.6)
      and monodehydroascorbate reductase (MDAR; EC 1.6.5.4) in SD seedlings was nearly
      the same as in AD seedlings. When SD seedlings were exposed to air, the activity
      of SOD, DHAR and GR increased, while the activity of catalase and MDAR decreased.
      Seven electrophoretically distinct SOD isozymes were detectable in N. nucifera.
      The levels of plastidic Cu,Zn-SODs and Fe-SOD in SD seedlings were comparable
      with those found in AD seedlings, which may reflect the maintenance of green
      plastids in SD seedlings as well as in AD seedlings. These results were
      substantially different from those previously found in rice seedlings germinated
      under water.

PMID- 11319014
TI  - Response of senescing cotyledons of clusterbean to water stress in moderate and
      low light: Possible photoprotective role of beta-carotene.
AB  - Senescence of clusterbean (Cyamopsis tetragonoloba L.) cotyledons in moderate
      light (12 W m-2) brings about a loss in the pigments, enhanced lipid peroxidation
      and a decline in PS II photochemical activity without any loss either in Dl
      protein or in the level of beta-carotene. The senescence syndrome is aggravated
      in the cotyledons of water-stressed seedlings with an increase in thylakoid lipid
      peroxidation, a decline in the level of beta-carotene and a quantitative loss in
      the Dl protein. Loss of the protein, however, is arrested in the seedlings
      experiencing water stress at low light (3 W m-2) intensity that correlates with
      the stability in the level of beta-carotene and a slow rate of lipid
      peroxidation. Loss of the protein in moderate light is attributed to water-stress
      sensitized photoinhibitory damage. The data on changes in the components of
      xanthophyll cycle suggest the low activity of the cycle both during senescence
      and water stress. It is, therefore, concluded that beta-carotene may contribute
      to the assembly and stability of the Dl protein during senescence and water
      stress in clusterbean cotyledons.

PMID- 11319015
TI  - Adjustments of net photosynthesis in Solanum tuberosum in response to reciprocal
      changes in ambient and elevated growth CO2 partial pressures.
AB  - Single leaf photosynthetic rates and various leaf components of potato (Solanum
      tuberosum L.) were studied 1-3 days after reciprocally transferring plants
      between the ambient and elevated growth CO2 treatments. Plants were raised from
      individual tuber sections in controlled environment chambers at either ambient
      (36 Pa) or elevated (72 Pa) CO2. One half of the plants in each growth CO2
      treatment were transferred to the opposite CO2 treatment 34 days after sowing
      (DAS). Net photosynthesis (Pn) rates and various leaf components were then
      measured 34, 35 and 37 DAS at both 36 and 72 Pa CO2. Three-day means of single
      leaf Pn rates, leaf starch, glucose, initial and total Rubisco activity, Rubisco
      protein, chlorophyll (a+b), chlorophyll (a/b), alpha-amino N, and nitrate levels
      differed significantly in the continuous ambient and elevated CO2 treatments.
      Acclimation of single leaf Pn rates was partially to completely reversed 3 days
      after elevated CO2-grown plants were shifted to ambient CO2, whereas there was
      little evidence of photosynthetic acclimation 3 days after ambient CO2-grown
      plants were shifted to elevated CO2. In a four-way comparison of the 36, 72, 36
      to 72 (shifted up) and 72 to 36 (shifted down) Pa CO2 treatments 37 DAS, leaf
      starch, soluble carbohydrates, Rubisco protein and nitrate were the only
      photosynthetic factors that differed significantly. Simple and multiple
      regression analyses suggested that negative changes of Pn in response to growth
      CO2 treatment were most closely correlated with increased leaf starch levels.

PMID- 11319016
TI  - Leaf cuticular waxes of potted rose cultivars as affected by plant development,
      drought and paclobutrazol treatments.
AB  - The present work was carried out to evaluate how plant growth and cultural
      practices influence the amount and composition of cuticular waxes on leaves of
      rose cultivars. The total amount of cuticular wax per leaf area was higher for
      rose cultivar Apollo Parade than for Charming Parade. Both cultivars had waxes
      dominated by alkanes, with the major alkanes being the C31 and C33 homologues.
      Primary alcohols were the next most abundant constituent class, with C26 as the
      dominant homologue. Compared with Charming Parade, Apollo Parade had higher
      proportions of its total wax load as primary alcohols but lower acids and
      aldehydes. The proportion of alkanes in the total load on these cultivars was
      similar. Commercially produced roses are routinely treated with paclobutrazol
      (PBZ) to retard growth. PBZ treatments caused a 10% increase in total wax load
      and changes in the proportions of certain wax constituents within 11 days of
      application. Notable was an increase in the total proportion of acids in the
      total load 25 days after PBZ application, primarily because of increased C28
      acids. An alternative method of retarding plant growth is production of roses
      under limited water availability. When Apollo Parade roses experienced periods of
      moderate drought stress during production, the wax load per leaf area increased
      14 and 8% above control levels at 24 and 38 days after imposition of drought,
      respectively. Drought caused similar changes in the proportions of individual wax
      constituents as did PBZ application.

PMID- 11319017
TI  - Effects of climatic warming on cold hardiness of some northern woody plants
      assessed from simulation experiments.
AB  - Effects of climatic warming on cold hardiness were investigated for some northern
      woody plants. In the first experiment, seedlings of Norway spruce (Picea abies
      [L.] Karst.), Scots pine (Pinus sylvestris L.) and lodgepole pine (Pinus contorta
      Dougl. var. latifolia Engelm.) were exposed to naturally fluctuating temperatures
      averaging -6 degrees C (ambient) and 0 degrees C (elevated) for 16 weeks in
      midwinter before they were thawed and re-saturated with water. In lodgepole pine,
      needle sugar concentrations had decreased by 15%, and the temperature needed to
      induce 10% injury to needles in terms of electrolyte leakage had increased by 6
      degrees C following treatment to elevated as compared with control temperatures.
      In contrast, Norway spruce and Scots pine showed no effects. The lack of an
      effect for Scots pine was ascribed to seedlings containing unusually large energy
      reserves that buffered respiratory expenditure of sugars. A strong, linear
      relationship between levels of cold hardiness, assessed by the electrolyte
      leakage method, and sugars was found when combining data from this and previous,
      similar experiments. In the second experiment, the evergreen dwarf shrub Empetrum
      hermaphroditum Hagerup was analysed for leaf cold hardiness, using the
      electrolyte leakage method, and sugar concentrations in late spring and late
      autumn during the third year of a warming experiment in a subarctic dwarf shrub
      community. The objective was to test the hypothesis that warming in the growing
      season alters hardening/dehardening cycles by increasing soil nitrogen
      mineralization and plant growth. Data found, however, suggested that cold
      hardening/dehardening cycles were unaffected by warming.

PMID- 11319018
TI  - Winter rye antifreeze activity increases in response to cold and drought, but not
      abscisic acid.
AB  - Antifreeze activity increases in winter rye (Secale cereale L.) during cold
      acclimation as the plants accumulate antifreeze proteins (AFPs) that are similar
      to glucanases, chitinases and thaumatin-like proteins (TLPs) in the leaf
      apoplast. In the present work, experiments were conducted to assess the role of
      drought and abscisic acid (ABA) in the regulation of antifreeze activity and
      accumulation of AFPs. Antifreeze activity was detected as early as 24 h of
      drought treatment at 20 degrees C and increased as the level of apoplastic
      proteins increased. Apoplastic proteins accumulated rapidly under water stress
      and reached a level within 8 days that was equivalent to the level of apoplastic
      proteins accumulated when plants were acclimated to cold temperature for 7 weeks.
      These drought-induced apoplastic proteins had molecular masses ranging from 11 to
      35 kDa and were identified as two glucanases, two chitinases, and two TLPs, by
      using antisera raised against cold-induced rye glucanase, chitinase, and TLP,
      respectively. Apoplastic extracts obtained from plants treated with ABA lacked
      the ability to modify the growth of ice crystals, even though ABA induced the
      accumulation of apoplastic proteins within 4 days to a level similar to that
      obtained when plants were either drought-stressed for 8 days or cold-acclimated
      for 7 weeks. These ABA-induced apoplastic proteins were identified
      immunologically as two glucanases and two TLPs. Moreover, the ABA biosynthesis
      inhibitor fluridone did not prevent the accumulation of AFPs in the leaves of
      cold-acclimated rye plants. Our results show that cold acclimation and drought
      both induce antifreeze activity in winter rye plants and that the pathway
      regulating AFP production is independent of ABA.

PMID- 11319019
TI  - Cloning, characterization and functional expression of a phospholipase Dalpha
      cDNA from tomato fruit.
AB  - Phospholipase D (PLD; EC 3.1.4.4) initiates phospholipid (PL) catabolism in plant
      cells and is also involved in signal transduction and retailoring of membrane PL.
      Phosphatidic acid (PA), the product of PLD hydrolysis of PL, increases in
      pericarp tissue during ripening of tomato (Lycopersicon esculentum Mill.) fruit,
      suggesting that increased PLD activity may be involved in loss of membrane
      function associated with ripening. However, a recent report showed a decline in
      soluble PLD activity in both normal and nonripening mutant fruit over the span
      that encompasses full ripening. To directly assess the role of PLD in tomato
      ripening, we have initiated a molecular genetic approach. Using a PLDalpha cDNA
      from castor bean as a probe, a PLDalpha cDNA (LEPLD2) was isolated from a tomato
      fruit library. It has an open reading frame of 2 421 nucleotides, predicted to
      encode a polypeptide of 807 amino acids, with a molecular mass of 91.9 kDa. These
      values are close to those of PLDalphas from 11 plant species and LEPLD2 has
      >/=73% nucleotide sequence identity with PLDalpha cDNAs from castor bean and
      tobacco, as well as another tomato cDNA. LEPLD2 transcript was detected in all
      tissues of the tomato plant by RNA gel-blot analysis. Levels were very low in
      roots, low in stems, moderate in leaves, high in flowers and increased in fruit
      during development and ripening. Expression of LEPLD2 in Escherichia coli yielded
      phosphatidylcholine-hydrolyzing enzyme, and cells transformed with a pFLAG-MAC
      vector construct produced a FLAG-PLDalpha fusion protein that migrated close to
      the calculated 94 kDa on sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis.

PMID- 11319020
TI  - Three MADS-box genes similar to APETALA1 and FRUITFULL from silver birch (Betula
      pendula).
AB  - Despite intensive research on genetic regulation of flower development there are
      still only a few studies on the early phases of this process in perennial plants
      like trees. The aim of this study has been to identify genes that regulate early
      stages of inflorescence development in silver birch (Betula pendula Roth) and to
      follow the expression of these genes during development of the unisexual birch
      inflorescences. Here we describe the cloning and characterization of 3 cDNAs
      representing MADS-box genes designated BpMADS3, BpMADS4 and BpMADS5, all
      belonging to the AP1/SQUA group of plant MADS-box genes. According to RNA blot
      analysis, all 3 genes are active during the development of both male and female
      inflorescences. However, differences in patterns of expression suggest that they
      play different roles. BpMADS3 is most similar in sequence to AP1 and SQUA, but it
      seems to have the highest expression at late developmental stages. BpMADS4 is
      most similar in sequence to the Arabidopsis gene FRUITFULL, but is expressed, in
      addition to developing inflorescences, in shoots and roots. BpMADS5 is also
      similar to FRUITFULL; its expression seems to be inflorescence-specific and
      continues during fruit development. Ectopic expression of either BpMADS3, BpMADS4
      or BpMADS5 with the CaMV 35S promoter in tobacco results in extremely early
      flowering. All of these birch genes seem to act early during the transition to
      reproductive phase and might be involved in the determination of the identity of
      the inflorescence or flower meristem. They could apparently be used to accelerate
      flowering in various plant species.

PMID- 11319021
TI  - Brassinosteroid-induced exaggerated growth in hydroponically grown Arabidopsis
      plants.
AB  - The effects of root application of brassinolide (BL) on the growth and
      development of Arabidopsis plants (Arabidopsis thaliana ecotype Columbia [L.]
      Heynh) were evaluated. Initially, all leaves were evaluated on plants 18, 22, 26
      and 29 days old. The younger leaves were found to exhibit maximal petiole
      elongation and upward leaf bending in response to BL treatment. Therefore, based
      on these results leaves 6, 7 and 8 on 22-24-day-old plants were selected for all
      subsequent studies. Elongation along the length of the petiole in response to BL
      treatment was uniform with the exception of an approximately 4 mm region next to
      the leaf where upward curvature was observed. Both BL and 24-epibrassinolide (24
      epiBL) were evaluated, with BL being more effective at lower concentrations than
      24-epiBL. The exaggerated growth induced by 0.1 uM BL was not observed in plants
      treated with 1 000-fold higher concentrations of GA3, IAA, NAA or 2,4-D (100 uM).
      In addition, no exaggerated growth effects were observed when plants were treated
      with 200 ppm ethylene or 1 mM ACC. All treatments with BL, NAA, 2,4-D, IAA or ACC
      promoted ethylene and ACC production in wild type Arabidopsis plants, but only BL
      triggered exaggerated plant growth. BL also promoted exaggerated growth and
      elevated levels of ACC and ethylene in the ethylene insensitive mutant etr1-3,
      showing that the effect of BR on growth is independent of ethylene. This work
      provides evidence that BR-induced exaggerated growth of Arabidopsis plants is
      independent of gibberellins, auxins and ethylene.

PMID- 11319022
TI  - Auxin modification of the incompatibility response in Theobroma cacao.
AB  - The time course and control of floral abscission and fruit set in Theobroma cacao
      were studied after spray application of growth regulators. 1-Naphthaleneacetic
      acid (NAA) prevented flower abscission in a concentration dependent manner and
      induced the early stages of fruit development. The cytokinin benzylaminopurine
      (BAP) counteracted NAA but resulted in longer fruit retention. Measurements of
      endogenous levels of indole-3-acetic acid showed an inverse correlation between
      the number of flowers per plant and auxin content. The results suggest that the
      genetic control of self-incompatibility in T. cacao may be modulated by the
      hormonal content of the flower.

PMID- 11319023
TI  - Lateral redistribution of auxin is not the means for gravitropic differential
      growth of coleoptiles: A new model.
AB  - Gravicurvature in water- and auxin (IAA)-incubated coleoptiles of rye (Secale
      cereale L.) is similar, despite a general strongly enhancing effect of exogenous
      IAA on the overall (cell) elongation of these organs. Longitudinally split
      coleoptiles or isolated longitudinally halved coleoptiles (horizontally
      positioned as upper or lower halves) respond gravitropically in the same way as
      water-incubated intact coleoptiles, irrespective of whether the halves are
      incubated in distilled water or IAA. A new model for the principal mechanism of
      regulation of gravitropic growth is proposed which depends on, yet does not
      involve, the redistribution of IAA as the means for gravistimulated differential
      growth, as postulated by the Cholodny-Went hypothesis (CWH). It is based on a
      gravimediated temporarily restrained infiltration of IAA-induced wall-loosening
      factors into the growth-limiting outer epidermal walls of the concave organ
      flank.

PMID- 11319024
TI  - Novel cytokinins: The predominant forms in mature buds of Pinus radiata.
AB  - To elicit the roles of cytokinins in the regulation of maturation of Pinus
      radiata D. Don, the spectrum of endogenous cytokinins and their concentration in
      the mature buds were analysed using double-solvent extraction, column complex
      purification and separation, a novel immunoaffinity purification method, normal
      and reverse phase high-pressure liquid chromatography, enzymatic treatment,
      radioimmunoassay and electrospray MS/MS spectrometry. We have isolated two novel
      cytokinin glycosides whose proposed structures are isopentenyladenine-9
      (glucopyranosyl riboside), dihydrozeatin-9-(glucopyranosyl riboside) and
      confirmed the presence of zeatin-9-(glucopyranosyl riboside). We have also found
      the presence of novel phosphorylated forms of these 3 cytokinin ribosyl-linked
      glycosides. Quantitative analyses revealed that the cytokinin ribosyl-linked
      glycosides predominate in P. radiata mature buds. Although cytokinin free base,
      riboside and nucleotide forms are also present, we could find no evidence of the
      traditional cytokinin O- or N-glucosides in the conifer buds. Thus, cytokinin
      metabolism in mature buds of P. radiata is very different from other species
      previously examined.

PMID- 11319025
TI  - Early detection of graft incompatibility in apricot (Prunus armeniaca) using in
      vitro techniques.
AB  - Graft compatibility has been studied in vitro using callus tissues of apricot
      (Prunus armeniaca) and different Prunus rootstocks to form scion/rootstock
      combinations with different degrees of graft compatibility. In these species,
      incompatibility is manifested by a breakdown of the trees at the union area that
      can occur some years after grafting. Here, the possibility of obtaining an early
      detection method to determine graft incompatibility is explored by callus fusion
      in vitro. The adhesion of the two callus partners, the development of the cells
      at the contact surface (cell arrangement, intensity of cell-wall staining), and
      the presence of lipid and phenolic compounds have been studied during the first 3
      weeks after grafting in both compatible and incompatible combinations.
      Differences were observed at the second and the third week of callus co-culture
      in most of the characters determined, although these differences were present as
      early as the first week in the case of phenolic compounds. The behaviour of the
      grafts grown in vitro was correlated to that of the same combinations in the
      field, suggesting that callus fusion in vitro could be a possible and reliable
      method for an early detection of graft incompatibility in different Prunus
      combinations.

PMID- 11319026
TI  - Increasing ploidy level in cell suspension cultures of Doritaenopsis by exogenous
      application of 2,4-dichlorophenoxyacetic acid.
AB  - To clarify the causal factors for ploidy variation in plant cell culture, we
      attempted to alter ploidy distribution in cell cultures of a tetraploid cultivar
      of Doritaenopsis by changing the plant growth regulators (PGRs) in the culture
      medium. The original suspension cultured cells, which had been maintained in
      medium containing 0.1 mg l-1 1-naphthaleneacetic acid and 1 mg l-1 benzyladenine,
      were transferred onto various gellan gum solidified media with a single
      application of PGRs, and the ploidy distributions of the cells were examined
      using flow cytometry analysis during 3 weeks of culture. Among the PGRs tested,
      2,4-dichlorophenoxyacetic acid (2,4-D) and 4-amino-3,5,6-trichloropicolinic acid
      caused a drastic reduction in the 4C-cell proportion in cell cultures with an
      increased cell proportion of 8C or higher C-values. In the case of 2,4-D
      application, a reduction of cell viability was observed. A decreasing proportion
      was also observed in the 8C-cell population accumulated by 2,4-D treatment,
      following transfer back to the medium containing the standard PGR composition.
      These results suggest that the exogenous application of 2,4-D arrested the cell
      cycle at G2 phase in the Doritaenopsis cells, and the removal of 2,4-D might
      induce further endoreduplication or recover the mitotic cycle of the G2-arrested
      cells.

PMID- 11319027
TI  - A potato tuber-expressed mRNA with homology to steroid dehydrogenases affects
      gibberellin levels and plant development.
AB  - Using cDNA-AFLP RNA fingerprinting throughout potato tuber development, we have
      isolated a transcript-derived fragment (TDF511) with strong homology to plant
      steroid dehydrogenases. During in vitro tuberization, the abundance profile of
      the TDF shows close correlation to the process of tuber formation. However, when
      tuberization is inhibited by the addition of gibberellins (GAs) to the growth
      medium, the appearance of TDF511 in the fingerprint is delayed, then steadily
      increases in intensity during later stages of development. TDF511 was used to
      isolate the corresponding cDNA (CB12). The DNA and deduced amino-acid sequences
      of the cDNA show high homology to a fruit-ripening gene from tomato, a series of
      steroid dehydrogenases, and the maize Ts2 gene. A section of the cDNA was cloned
      in antisense orientation behind a 35S CaMV promoter and transformed into potato.
      Transgenic plants expressing the antisense gene showed significantly earlier
      emergence, an increase in height, and longer tuber shape. In vitro tuberization
      experiments reveal extended stolon lengths in comparison to the controls. The
      analysis of endogenous GA levels showed that the transgenic antisense plants have
      elevated levels of biologically active GAs and their respective precursors. We
      propose that this gene plays a role in the metabolism of plant-growth substances
      important for tuber life cycle and plant development.

PMID- 11319028
TI  - The ratio of campesterol to sitosterol that modulates growth in Arabidopsis is
      controlled by STEROL METHYLTRANSFERASE 2;1.
AB  - The Arabidopsis genome contains three distinct genes encoding sterol-C24
      methyltransferases (SMTs) involved in sterol biosynthesis. The expression of one
      of them, STEROL METHYLTRANSFERASE 2;1, was modulated in 35S:SMT2;1 Arabidopsis in
      order to study its physiological function. Plants overexpressing the transgene
      accumulate sitosterol, a 24-ethylsterol which is thought to be the typical plant
      membrane reinforcer, at the expense of campesterol. These plants displayed a
      reduced stature and growth that could be restored by brassinosteroid treatment.
      Plants showing co-suppression of SMT2;1 were characterized by a predominant 24
      methylsterol biosynthetic pathway leading to a high campesterol content and a
      depletion in sitosterol. Pleiotropic effects on development such as reduced
      growth, increased branching, and low fertility of high-campesterol plants were
      not modified by exogenous brassinosteroids, indicating specific sterol
      requirements to promote normal development. Thus SMT2;1 has a crucial role in
      balancing the ratio of campesterol to sitosterol in order to fit both growth
      requirements and membrane integrity.

PMID- 11319029
TI  - CKS1At overexpression in Arabidopsis thaliana inhibits growth by reducing
      meristem size and inhibiting cell-cycle progression.
AB  - The SUC1/CKS1 proteins associate with cyclin-dependent kinases (CDKs) and play an
      essential role in the regulation of the cell cycle. Recently, an Arabidopsis
      thaliana SUC1/CKS1 homologous gene, designated CKS1At, has been cloned. Here,
      overexpression of CKS1At in Arabidopsis is shown to reduce leaf size and root
      growth rates. Reduced root growth resulted primarily from an increase of the cell
      cycle duration and a shortening of the meristem. Endoreduplication was
      unaffected. The increased cell-cycle duration was associated with an equal
      extension of both the G1 and G2 phases. This inhibition was due to the binding of
      CDK subunits with CDKs. The reduced growth rates in response to altered cell
      cycle gene expression demonstrates a direct dependence of plant growth rates on
      cell-cycle regulation.

PMID- 11319030
TI  - Extensive developmental and metabolic alterations in cybrids Nicotiana tabacum (+
      Hyoscyamus niger) are caused by complex nucleo-cytoplasmic incompatibility.
AB  - The genetic basis of multiple phenotypic alterations was studied in cell
      engineered cybrids Nicotiana tabacum (+ Hyoscyamus niger) combining the nuclear
      genome of N. tabacum, plastome of H. niger and recombinant mitochondria. The
      plants possess a complex, maternally inheritable syndrome of nucleo-cytoplasmic
      incompatibility, severely affecting growth, metabolism and development. In vivo,
      the syndrome was manifested as: late germination of seeds; dramatic decrease of
      chlorophyll and carotenoids in cotyledons and leaves; altered morphology of
      cotyledons, leaves and flowers; and dwarfism. The leaf phenotype depended on
      light intensity. In 'green flowers' (an extreme phenotype), homeotic function B
      was downregulated. In vitro, the incompatibility syndrome was restricted to the
      pigment deficiency of cotyledons. Electron microscopy revealed perturbations in
      the differentiation of chloroplasts and palisade parenchyma cells in bleached
      leaves. The pigment deficiency accompanied by retarded growth is discussed as a
      result of plastome-genome incompatibility, whereas other features are likely to
      be due to nucleo-mitochondrial incompatibilities.

PMID- 11319031
TI  - Extracellular secretion of Aspergillus phytase from Arabidopsis roots enables
      plants to obtain phosphorus from phytate.
AB  - Phosphorus (P) deficiency in soil is a major constraint for agricultural
      production worldwide. Despite this, most soils contain significant amounts of
      total soil P that occurs in inorganic and organic fractions and accumulates with
      phosphorus fertilization. A major component of soil organic phosphorus occurs as
      phytate. We show that when grown in agar under sterile conditions, Arabidopsis
      thaliana plants are able to obtain phosphorus from a range of organic phosphorus
      substrates that would be expected to occur in soil, but have only limited ability
      to obtain phosphorus directly from phytate. In wild-type plants, phytase
      constituted less than 0.8% of the total acid phosphomonoesterase activity of root
      extracts and was not detectable as an extracellular enzyme. By comparison, the
      growth and phosphorus nutrition of Arabidopsis plants supplied with phytate was
      improved significantly when the phytase gene (phyA) from Aspergillus niger was
      introduced. The Aspergillus phytase was only effective when secreted as an
      extracellular enzyme by inclusion of the signal peptide sequence from the carrot
      extensin (ex) gene. A 20-fold increase in total root phytase activity in
      transgenic lines expressing ex::phyA resulted in improved phosphorus nutrition,
      such that the growth and phosphorus content of the plants was equivalent to
      control plants supplied with inorganic phosphate. These results show that
      extracellular phytase activity of plant roots is a significant factor in the
      utilization of phosphorus from phytate and indicate that opportunity exists for
      using gene technology to improve the ability of plants to utilize accumulated
      forms of soil organic phosphorus.

PMID- 11319032
TI  - Gastrodianin-like mannose-binding proteins: a novel class of plant proteins with
      antifungal properties.
AB  - The orchid Gastrodia elata depends on the fungus Armillaria mellea to complete
      its life cycle. In the interaction, fungal hyphae penetrate older, nutritive
      corms but not newly formed corms. From these corms, a protein fraction with in
      vitro activity against plant-pathogenic fungi has previously been purified. Here,
      the sequence of gastrodianin, the main constituent of the antifungal fraction, is
      reported. Four isoforms that encoded two different mature proteins were
      identified at the cDNA level. Another isoform was detected in sequenced peptides.
      Because the antifungal activity of gastrodianins produced in and purified from
      Escherichia coli and Nicotiana tabacum was comparable to that of gastrodianin
      purified from the orchid, gastrodianins are the active component of the
      antifungal fractions. Gastrodianin accumulation is probably an important part of
      the mechanism by which the orchid controls Armillaria penetration. Gastrodianin
      was found to be homologous to monomeric mannose-binding proteins of other
      orchids, of which at least one (Epipactis helleborine mannose-binding protein)
      also displayed in vitro antifungal activity. This establishes the gastrodianin
      like proteins (GLIPs) as a novel class of antifungal proteins.

PMID- 11319033
TI  - Novel marker genes for early leaf development indicate spatial regulation of
      carbohydrate metabolism within the apical meristem.
AB  - To identify genes expressed at the earliest stages of leaf development, we have
      performed a differential display analysis using portions of meristems destined to
      form leaves. Our analysis led to the identification of five genes showing an
      asymmetric pattern of gene expression within the meristem associated with leaf
      formation. Surprisingly, three of these genes encoded enzymes involved in
      carbohydrate metabolism (ADPglucose pyrophosphorylase, sucrose synthase and an
      SNF1-like kinase). Furthermore, specific transcript patterns were responsive to
      specific sugar and hormonal treatments. The other two genes identified encoded a
      Phantastica-like myb transcription factor (associated with the acquisition of
      leaf dorsiventrality) and CYP85 (a cytochrome P450, which plays a pivotal role in
      brassinolide metabolism). These data, firstly, identify a novel set of marker
      genes for the analysis of the earliest stages of leaf formation. Secondly, the
      function of the proteins encoded by these genes and their expression patterns
      within the meristem indicate that carbohydrate metabolism is spatially regulated
      within a tissue involved in key developmental processes. Finally, our data
      provide the first indication of an asymmetry in gene expression related to
      hormone biosynthesis in the meristem.

PMID- 11319034
TI  - Interactions within a network of phytochrome, cryptochrome and UV-B
      phototransduction pathways regulate chalcone synthase gene expression in
      Arabidopsis leaf tissue.
AB  - The Arabidopsis gene encoding the key flavonoid biosynthesis enzyme chalcone
      synthase (CHS) is regulated by several environmental and endogenous stimuli. Here
      we dissect the network of light signalling pathways that control CHS expression
      in mature leaves using cryptochrome (cry) and phytochrome (phy) deficient
      mutants. The UV-A/blue light induction of CHS is mediated principally by cry1,
      but neither cry1 nor cry2 is involved in UV-B induction or in the UV-A and blue
      light signalling pathways that interact synergistically with the UV-B pathway to
      enhance CHS expression. Moreover, these synergistic responses do not require phyA
      or phyB. Phytochrome is a positive regulator of the cry1 inductive pathway,
      mediating distinct potentiation and coaction effects. A red light pretreatment
      enhances subsequent cry1-mediated CHS induction. This potentiation is unaltered
      in phyA and phyB mutants but much reduced in a phyA phyB double mutant,
      indicating that it requires principally phyA or phyB. In contrast, the cry1
      mediated induction of CHS, without pretreatment, is much reduced in phyB but not
      phyA mutants, indicating coaction between cry1 and phyB. Further experiments with
      phy-deficient mutants demonstrate that phyB is a negative regulator of the UV-B
      inductive pathway. We further show that phyB acts upstream of the points of
      interaction of the UV-A and blue synergism pathways with the UV-B pathway. We
      propose that phyB functions to balance flux through the cry1 and UV-B signalling
      pathways.

PMID- 11319035
TI  - Maize endosperm secretes a novel antifungal protein into adjacent maternal
      tissue.
AB  - A series of endosperm transfer layer-specific transcripts has been identified in
      maize by differential screening of a cDNA library of transcripts at 10 days after
      pollination. Sequence comparisons revealed among this class of cDNAs a novel,
      small gene family of highly diverged sequences encoding basal layer antifungal
      proteins (BAPs). The bap genes mapped to two loci on chromosomes 4 and 10. So
      far, bap-homologous sequences have been detected only in maize, teosinte and
      sorghum, and are not present in grasses outside the Andropogoneae tribe. BAP2 is
      synthesized as a pre-proprotein, and is processed by successive removal of a
      signal peptide and a 29-residue prodomain. The proprotein can be detected
      exclusively in microsomal membrane-containing fractions of kernel extracts.
      Immunolocalization reveals BAP2 to be predominantly located in the
      placentochalazal cells of the pedicel, adjacent to the basal endosperm transfer
      layer (BETL) cells, although the BAP2 transcript is found only in the BETL cells.
      The biological roles of BAP2 propeptide and mature peptide have been investigated
      by heterologous expression of the proprotein in Escherichia coli, and by tests of
      its fungistatic activity and that of the fully processed form in vitro. The
      mature BAP2 peptide exhibits potent broad-range activity against a range of
      filamentous fungi, including several plant pathogens.

PMID- 11319036
TI  - Localization of single-copy T-DNA insertion in transgenic shallots (Allium cepa)
      by using ultra-sensitive FISH with tyramide signal amplification.
AB  - The sensitivity of fluorescence in situ hybridization (FISH) for mapping plant
      chromosomes of single-copy DNA sequences is limited. We have adapted for plant
      cytogenetics a new signal-amplification method termed tyramide-FISH (Tyr-FISH).
      Until present this technique has only been applied to human chromosomes. The
      method is based on enzymatic deposition of fluorochrome-conjugated tyramide. With
      Tyr-FISH it was possible to detect target T-DNA sequences on plant metaphase
      chromosomes as small as 710 bp without using a cooled CCD camera. Short detection
      time and high sensitivity, in combination with a low background, make the Tyr
      FISH method very suitable for routine application in plant cytogenetic research.
      With Tyr-FISH we analysed the position of T-DNA inserts in transgenic shallots.
      We found that the inserts were preferentially located in the distal region of
      metaphase chromosomes. Sequential fluorescence in situ hybridization with a 375
      bp satellite sequence suggested that a specific T-DNA insert was located within
      the satellite sequence hybridization region on a metaphase chromosome. Analysis
      of less-condensed prophase and interphase chromosomes revealed that the T-DNA was
      integrated outside the satellite DNA-hybridization region in a more proximal
      euchromatin region.

PMID- 11319037
TI  - Normal embryonic stages of the longnose gar, Lepisosteus osseus.
AB  - BACKGROUND: Gaps exist in the modern literature that describes patterns of
      development in living groups of actinopterygian fishes. Relatively recent
      descriptions of development exist for the teleost fishes, bowfin, sturgeon,
      paddlefish and bichirs. Such literature dealing with the gars is to be found in
      older work, done approximately a century ago. The present study concerns the
      gars, of which the garpike, Lepisosteus osseus, is a representative example.
      RESULTS: The embryonic period of life of this fish is divided, as required for
      experimentation, into 34 stages, from fertilization to exhaustion of the yolk
      supply. Diagnostic structural characteristics are cited for each stage, and the
      rate of development is indicated. CONCLUSIONS: Three features of development are
      especially noted that compare or contrast with other members of the Neopterygii,
      and with the Chondrostei. These are meroblastic cleavage, a well-defined yolk
      syncytial layer (ysl), and a pit at the posterodorsal edge of the blastoderm,
      which defines an overhanging dorsal lip. Meroblastic cleavage and the ysl in the
      garpike show an affinity to those character states in the teleosts, though not
      with Amia, the other neopterygian fish. The posterodorsal pit and dorsal lip are
      reminiscent of similar features in the Chondrostei. Lepisosteus is unique among
      the Neopterygii with respect to this character state. Such comparisons set the
      stage for a broader understanding of the mechanisms for development in these
      organisms, and of the evolutionary relationships between them.

PMID- 11319039
TI  - EDITORIAL.

PMID- 11319038
TI  - Tumor necrosis factor and lymphotoxin-alpha genetic polymorphisms and risk of
      relapse in childhood B-cell precursor acute lymphoblastic leukemia: a case
      control study of patients treated with BFM therapy.
AB  - BACKGROUND: Circulating levels of tumor necrosis factor (TNF) and lymphotoxin
      alpha (LT-alpha) have been associated with outcome in solid and hematologic
      malignancies. Within the TNF gene and the LT-alpha gene, polymorphisms have been
      identified at nucleotide positions -308 and +252, respectively. The variant
      alleles for TNF are designated TNF1 and TNF2, the ones for LT-alpha LT-alpha
      (10.5 kb) and LT-alpha (5.5 kb). Of interest, TNF2 and LT-alpha (5.5 kb) were
      shown to be associated with higher TNF and LT-alpha plasma levels than their
      counterparts. In the present study, we investigated the associations of the above
      mentioned polymorphisms with risk of relapse in childhood acute lymphoblastic
      leukemia (ALL) treated according to Berlin-Frankfurt-Munster (BFM) protocols.
      METHODS: Matched case-control study of 64 relapsed and 64 successfully treated
      non-relapsed childhood B-cell precursor ALL patients of standard and intermediate
      risk for treatment failure. RESULTS: The odds ratio (OR) for the combined
      category of TNF1/TNF2 and TNF2/TNF2 genotypes in comparison to the TNF1/TNF1
      genotype was 1.17 (95 % confidence interval (CI) = 0.53 - 2.56, P = 0.697). The
      ORs for the LT-alpha (10.5 kb/5.5 kb) and the LT-alpha (5.5 kb/5.5 kb) genotypes
      with reference to the LT-alpha (10.5 kb/10.5 kb) genotype were 2.17 (95 % CI =
      0.84 - 5.58, P = 0.107) and 0.5 (95 % CI = 0.09 - 2.66, P = 0.418), respectively.
      CONCLUSIONS: Our results do not suggest a major role of the investigated genetic
      polymorphisms with regard to risk of relapse in standard- and intermediate-risk
      childhood B-cell precursor ALL treated according to BFM protocols.

PMID- 11319040
TI  - The evolving role of radical surgery in the management of regionally advanced
      transitional cell carcinoma of the bladder.
AB  - The management of muscle-invasive transitional cell carcinoma (TCC) of the
      bladder continues to evolve. The standard treatment for patients presenting with
      clinical stage T2-4aN0M0 bladder cancer remains radical cystectomy. However, the
      management of patients who present with more advanced disease on clinical
      evaluation, such as unresectable pelvic tumor (T4b) or regional pelvic lymph node
      metastases (N+) remains unclear. In addition, the intraoperative management of
      unsuspected pelvic adenopathy identified during exploration of a planned radical
      cystectomy, continues to generate controversy. The following discussion relates
      to the evolving attitudes towards the role of surgery in the treatment of
      advanced bladder cancer.

PMID- 11319041
TI  - Treatment of cyclophosphamide induced hemorrhagic cystitis with hyperbaric
      oxygen: a case report.
AB  - Hemorrhagic cystitis is a well known complication of treatment with
      cyclophosphamide. We describe a case of refractory cyclophosphamide induced
      hemorrhagic cystitis treated successfully with hyperbaric oxygen.

PMID- 11319042
TI  - Angiographic management of pseudoaneurysm and arteriocalyceal fistula following
      blunt trauma: case report and review of the literature.
AB  - We report a case of blunt trauma causing both a pseudoaneurysm and an
      arteriocalyceal fistula. These 2 lesions have not previously been reported
      occurring simultaneously as a complication of renal trauma. Pathophysiology,
      clinical presentation, and management options are discussed. Angiography in this
      case was both diagnostic and therapeutic. Selective and superselective gelfoam
      embolization led to immediate resolution of both injuries.

PMID- 11319043
TI  - Resident education outcomes and perception of a seminar format to teach female
      pelvic anatomy and procedures to correct pelvic prolapse.
AB  - Urologic residents need to learn basic and applied knowledge of female pelvic
      anatomy, a subject rarely taught beyond preclinical undergraduate medical
      education. This study tests the hypothesis that urologic resident knowledge of
      female pelvic anatomy and prolapse may be enhanced with a seminar. Twenty
      residents attended a one day seminar combining didactics and a cadaveric
      dissection related to female pelvic anatomy and female pelvic prolapse
      conditions. Resident knowledge was measured with a multiple choice test
      administered in a pretest-posttest experimental design. Resident attitudes toward
      the seminar were assessed by a 20 item survey using a strongly disagree to
      strongly agree scale. Pretest and posttest mean scores were 55% and 71%
      respectively, p=.0007 (Kuder-Richardson 20 coefficients were 0.7). Questionnaire
      responses indicated positive opinions regarding the educational value of the
      seminar. Urologic resident knowledge of female pelvic anatomy and pelvic prolapse
      conditions may be enhanced by conducting a one day teaching seminar.

PMID- 11319044
TI  - Re: Meta-analysis and economic evaluation of LH-RH agonists' depot formulations
      in advanced prostatic carcinoma.

PMID- 11319045
TI  - Re: Meta-analysis and economic evaluation of LH-RH agonists' depot formulations
      in advanced prostatic carcinoma.

PMID- 11319046
TI  - Reply by author, Re: Meta-analysis and economic evaluation of LH-RH agonists'
      depot formulations in advanced prostatic carcinoma.

PMID- 11319047
TI  - Reply by editor, Re: Meta-analysis and economic evaluation of LH-RH agonists'
      depot formulations in advanced prostatic carcinoma.

PMID- 11319048
TI  - Cancer risk from low-level ionizing radiation: the role of age at exposure.
AB  - This article examines methodological issues related to epidemiologic
      investigations of the influence of age at exposure on radiation risk estimates;
      the epidemiologic literature on the role of age at exposure in radiation-cancer
      associations; and biological mechanisms that may account for associations
      observed in these studies. There is substantial evidence that young children, and
      especially the fetus, are highly vulnerable to ionizing radiation. Investigations
      also suggest that sensitivity may increase at the oldest ages of exposure.
      Further attention to modifying factors in radiation-cancer associations, such as
      age at exposure, may help to protect workers and the public by improving our
      understanding of sensitivity variation within populations.

PMID- 11319049
TI  - Effects of radiation and chemical exposures on cancer mortality among Rocketdyne
      workers: a review of three cohort studies.
AB  - The purpose of the UCLA Rocketdyne Study was to estimate the effects of
      occupational exposures to low-level ionizing radiation and selected chemicals on
      cancer mortality among nuclear and aerospace workers who were employed at
      Rocketdyne/Atomics International between 1950 and 1993. The results of this
      retrospective cohort study suggest that: (1) exposure to external radiation,
      especially doses greater than 200 mSv, increased the risk of dying from
      lymphopoietic cancers, lung cancer, and possibly other solid cancers; (2)
      exposure to internal radiation increased the risk of dying from lymphopoietic
      cancers and upper-aerodigestive-tract cancers; and (3) exposure to hydrazine or
      other chemicals associated with the same jobs at rocket-engine test stands
      increased the risk of dying from lung cancer and possibly other cancers.

PMID- 11319050
TI  - Improving estimates of exposures for epidemiologic studies of plutonium workers.
AB  - Epidemiologic studies of nuclear facilities usually focus on relations between
      cancer and doses from external penetrating radiation, and describe these
      exposures with little detail on measurement error and missing data. We
      demonstrate ways to document complex exposures to nuclear workers with data on
      external and internal exposures to ionizing radiation and toxic chemicals. We
      describe methods for assessing internal exposures to plutonium and external doses
      from neutrons; the use of a job exposure matrix for estimating chemical
      exposures; and methods for imputing missing data for exposures and doses. For
      plutonium workers at Rocky Flats, errors in estimating neutron doses resulted in
      underestimating the total external dose for production workers by about 16%.
      Estimates of systemic deposition do not correlate well with estimates of organ
      doses. Only a small percentage of workers had exposures to toxic chemicals,
      making epidemiologic assessments of risk difficult.

PMID- 11319051
TI  - Health risks from radium in workplaces: an unfinished story.
AB  - The classic health effects of occupational exposure to radium include
      osteosarcomas and fibrosarcomas of bone, carcinomas of paranasal sinuses and
      mastoid air cells, and microscopically and radiographically evident lesions of
      bone, along with fractures in highly exposed individuals. Among probable effects
      are breast cancer and acceleration of cataracts. Thyroid carcinoma is a possible
      high-dose effect. Leukemia is likely related to employment in the radium
      industry. Multiple myeloma and excess lung cancer may have resulted from high
      gamma radiation and radon exposures rather than from internal radium. At high
      doses, impairment of fertility has occurred. Further investigations of effects on
      the cardiovascular system and hearing, and on fracture-related disability very
      late in life, are needed.

PMID- 11319052
TI  - Leukemia mortality among radiation-exposed workers.
AB  - The qualitative leukemogenicity of ionizing radiation was firmly established by
      studies of medical workers and patients exposed to high radiation levels in the
      mid-1900s. Quantitative relationships were evaluated through extensive studies of
      atomic bomb survivors and patients who received therapeutic radiation, for whom
      the duration of exposure was brief. Although many studies have been conducted of
      nuclear workers and others exposed occupationally, uncertainty remains about
      quantitative aspects of the leukemia-radiation exposure relation for low dose
      rate, fractionated exposures. Some studies have shown dose-related increases in
      leukemia risks for certain nuclear workers in the U.S. and Europe, although these
      findings are inconsistent across populations. Despite limitations in low-dose
      epidemiology, well-designed studies among nuclear workers should inform some
      controversial aspects of the relation between ionizing radiation exposure and
      leukemia risk.

PMID- 11319053
TI  - Reappraisal of brain tumor risk among U.S. nuclear workers: a 10-year review.
AB  - A review of cohort mortality studies among workers exposed to ionizing radiation
      in U.S. nuclear programs was published in this journal 10 years ago. The present
      review extends that investigation to include four new groups of workers at
      Fernald (Ohio), Rocketdyne/Atomics International (California), Mallinckrodt
      Chemical (Missouri), and Los Alamos National Laboratory (New Mexico). The total
      number of brain tumors has doubled to nearly 300, with 3.8 million person-years
      of observation among 140,000 U.S. white male workers. This increased risk of
      brain tumor is highly consistent, persistent, and stable. The sum total of these
      studies dwarfs the reported experience of any other comparison group. The
      observed increased brain tumor risk is statistically significant and has changed
      little since 1991 when it was estimated at 15%. Study results from 1999 and 2000
      may suggest a modest growing risk of 25-30%.

PMID- 11319054
TI  - Tissue studies of persons with intakes of the actinide elements: the U.S.
      Transuranium and Uranium Registries.
AB  - For more than three decades, the United States Transuranium and Uranium
      Registries (USTUR) have studied the biokinetics, dosimetry, and biological
      effects of plutonium, uranium, and americium through voluntary postmortem tissues
      from persons with known intakes. Radiochemical analyses of tissue obtained at
      autopsy have shown that plutonium and americium have different biokinetics and an
      appreciable deposition in the soft tissues of the body as well as the known
      depots in skeleton and liver. Studies of whole-body Thorotrast donors to the
      USTUR indicate that commonly accepted risk coefficients for alpha induction of
      bone sarcoma may be too high while those for leukemia are a factor of six too
      low. This review considers these and other major contributions of the USTUR.

PMID- 11319055
TI  - Health effects in underground uranium miners.
AB  - The health effects associated with uranium miners have received much attention in
      the last 30 years. Although mortality rates are elevated for such causes as
      accidents and nonmalignant respiratory disease, lung cancer caused by exposure to
      radon decay products is the primary hazard to underground uranium miners. This
      review summarizes studies of eight cohorts of radium miners, and examines several
      pooled analyses that provide the best understanding of the radon/lung cancer
      relationship. The relative risk of lung cancer is linearly related to cumulative
      exposure to radon decay products. The excess relative risk decreases with
      attained age and time since exposure. An inverse exposure-rate effect exists,
      such that prolonged exposure at low levels of radon is more hazardous than
      shorter exposures to higher levels. The linear no-threshold model used in most
      epidemiologic studies has been attacked by some as overestimating risk at indoor
      radon levels. These arguments are rejected by this reviewer.

PMID- 11319056
TI  - Cytogenetic assays for monitoring populations exposed to environmental mutagens.
AB  - A variety of cytogenetic assays have been used successfully for monitoring
      populations exposed to environmental mutagens. The traditional chromosome
      aberration (CA) assay is one of the most useful, and it also predicts cancer
      outcome on a population basis. However, the sensitivity of this assay requires
      improvement, and researchers need to understand other factors that influence the
      expression of CA and health outcome, especially on an individual basis. The
      sensitivity and specificity of the CA assay are improved with the use of the
      fluorescence in situ hybridization (FISH) procedure, which employs a variety of
      chromosome-specific and chromosome region-specific fluorescence probes to
      elucidate CA. Factors that influence the expression of CA in a population study
      include inadequate study design, genetic variations in metabolism of chemicals
      (genetic susceptibility), and lifestyle differences in response to exposure to
      environmental mutagens (acquired susceptibility). The latter may involve previous
      or concurrent exposure to environmental mutagens, e.g., cigarette smoking habits.

PMID- 11319057
TI  - Characteristics of the healthy worker effect.
AB  - The healthy worker effect (HWE), which can mask mortality excesses resulting from
      occupational exposures, poses a methodological problem for those who study
      occupational cohorts. This problem is further complicated by the fact that the
      strength of the HWE may vary from one occupational cohort to another.
      Understanding the HWE is particularly important for investigators of nuclear
      worker cohorts, because screening associated with the security clearance process
      may amplify the HWE among certain subpopulations of nuclear workers. This review
      suggests that the HWE is modified by a number of factors, including gender, race,
      age at hire, occupational class, length of employment, monitored status, length
      of follow-up, and cause of death. In general, these factors operate similarly in
      nuclear and other occupational cohorts. Given that many of these factors may be
      highly correlated with exposure, or proxy measurements for exposure, it is
      important for investigators to understand how these factors relate independently
      with mortality. Continuing to document the HWE and its changes over time is
      essential to the proper interpretation of exposure effects in occupational
      cohorts in general, and in nuclear cohorts in particular.

PMID- 11319058
TI  - Historical perspective of achalasia.
AB  - This article provides an overview of the historic background of achalasia. It
      describes how achalasia was first chronicled in the 17th century. Prevalent
      theories of etiology from the original description to present day constructs are
      examined. Important individuals and their contributions to the concepts of
      achalasia are reviewed and various nonsurgical and surgical therapeutic
      techniques from antiquity to today are presented.

PMID- 11319059
TI  - Epidemiology and demographics of achalasia.
AB  - The incidence and prevalence of achalasia has been reported from a limited number
      of centers in the US, UK, Israel, Zimbabwe, Singapore, and New Zealand. With two
      exceptions, the studies have been retrospective. The incidence of the disease is
      about 0.5/10(5)/year with a prevalence of about 8/10(5) population. However,
      there appear to be striking international variations and also significant
      differences within countries. The disease occurs with equal frequency in men and
      women and is commoner with ageing. The appearance of the disease in the older age
      groups together with the lack of evidence for an autosomal recessive pattern of
      inheritance would suggest that environmental factors are important in the cause
      of the disease.

PMID- 11319060
TI  - Etiology and pathogenesis of achalasia.
AB  - The primary pathophysiologic abnormality in achalasia is loss of intrinsic
      inhibitory innervation of the lower esophageal sphincter and smooth muscle
      segment of the esophageal body. Disease of the extrinsic (vagal) nervous system
      and esophageal musculature may also be present, but these are less consistent
      findings and could represent secondary phenomena. Inflammation within the
      esophageal myenteric plexus is pathognomonic of the disease, but the cause of
      this inflammation is uncertain. Autoimmunity and previous viral infection have
      been hypothesized, but remain unproven.

PMID- 11319061
TI  - Diseases associated with or mimicking achalasia.
AB  - Achalasia may be associated with some rare systemic diseases. In addition, a few
      conditions produce a syndrome often indistinguishable from achalasia. Most of
      these diseases are malignant and should be considered in the differential
      diagnosis of idiopathic achalasia.

PMID- 11319062
TI  - Clinical presentations and complications of achalasia.
AB  - Patients with achalasia often present with atypical symptoms. If these occur in
      the context of "normal" morphological findings, the diagnosis may be delayed for
      several years. However, a careful interview and the use of modern methods that
      concentrate on pathophysiologic aspects always allow an early diagnosis and the
      initiation of therapy that affects most but rarely all symptoms. Finally,
      regardless of whether this therapy remains partially or totally effective,
      patients require some follow-up since serious and late complications may occur.

PMID- 11319063
TI  - Diagnostic modalities for achalasia.
AB  - Diagnostic evaluation for achalasia in patients with dysphagia begins with barium
      esophagography to evaluate for an anatomic lesion of the esophagus or the gastric
      fundus. Most of the patients with achalasia can be detected with an initial
      radiologic approach. Esophageal manometry, however, remains the gold standard for
      the diagnosis of achalasia and is important for patients for whom a correct
      diagnosis is uncertain or essential. The article reviews these and other
      diagnostic tests that may be used in evaluating patients suspected of having
      achalasia.

PMID- 11319064
TI  - Pharmacologic therapy in treating achalasia.
AB  - This article focuses on the different pharmacologic treatments for achalasia.
      Most smooth muscle relaxants such as nitrates and calcium antagonists are
      temporizing at best. Botulinum toxin, acting at the neuronal level, is effective
      in two thirds of the patients and has a duration of action of several months. It
      may be particularly suitable for the elderly or high-risk patient. The mechanism
      of action and efficacy of the different drugs are discussed in detail.

PMID- 11319065
TI  - Pneumatic balloon dilation for esophageal achalasia.
AB  - Pneumatic balloon dilation remains the medical treatment of choice for patients
      with achalasia. It is superior to other medical therapies including
      intrasphincteric botulinum toxin injection. The overall efficacy rate for long
      term excellent or good result is 80 to 85%. It is extremely important that the
      endoscopist be quite experienced in the technique of pneumatic dilation and
      develop a standard protocol to minimize the complications. The technique of
      graded balloon dilation starting with 3.0-cm Rigiflex balloon as the initial
      dilator and progressing to 3.5-cm and 4.0-cm balloon in absence of response to
      previous balloon size offers the safest approach. Patients not responding to
      three serial dilations should be offered surgery, although some patients may
      prefer repeat dilations to surgery. The overall complication rate for Rigiflex
      dilation is about 3% and for Witzel dilation is about 6%. Some patients will
      develop GER when measured by 24-hour esophageal pH monitoring, but most patients
      remain asymptomatic.

PMID- 11319066
TI  - Laparoscopic myotomy: technique and efficacy in treating achalasia.
AB  - Esophageal Heller myotomy and a partial antireflux procedure for achalasia are
      the ideal procedures to benefit from the advances in minimally invasive surgery.
      The magnified view of the operative field provided by the laparoscope allows
      precise division of the esophageal muscle fibers with excellent results.
      Laparoscopic Heller myotomy results in reduced postoperative pain, less
      morbidity, shorter hospitalization, better resolution of dysphagia, and less
      postoperative heartburn when compared with the open abdominal and even the
      thoracoscopic approach. A longer myotomy especially at the distal end, and a
      loose, well-formed partial fundoplication are the keys to a successful outcome.
      Superior long-term results after surgical myotomy when compared with nonsurgical
      interventions argue strongly in favor of surgery in any patient who is fit enough
      to undergo general anesthesia.

PMID- 11319067
TI  - Comparison and cost analysis of different treatment strategies in achalasia.
AB  - Currently there are three acceptable long-term treatments of achalasia: pneumatic
      dilatation, laparoscopic Heller myotomy, and botulinum toxin injection. Primarily
      retrospective studies suggest equal efficacy of pneumatic dilatation and surgical
      myotomy, especially in centers with expertise in both treatments. Randomized
      prospective studies find pneumatic dilatation superior to botulinum toxin because
      of the need for serial frequent treatments with the latter therapy. All cost
      analysis studies support the superiority of pneumatic dilatation over the two
      other treatments.

PMID- 11319068
TI  - Strategies for treating severe refractory dysphagia.
AB  - Traditional treatment of achalasia, pneumatic dilatation or surgical myotomy,
      results in satisfactory relief of dysphagia in 85% to 90% of patients.
      Unfortunately, a small percentage of patients do not respond to these therapies
      or remain refractory, often because of a severely dilated or sigmoid esophagus.
      Esophagectomy, with gastric pull up or color interposition, is the procedure of
      choice in these patients, which can result in satisfactory relief of dysphagia
      with minimal mortality. This article reviews the strategies for management of
      achalasia patients with refractory dysphagia.

PMID- 11319070
TI  - Quantitative methods to determine efficacy of treatment in achalasia.
AB  - Determining success after achalasia therapy is an important aspect of treating
      this disease. Esophageal manometry, scintigraphy, and barium esophagram are the
      most commonly employed techniques. Recent data suggest that barium esophagram may
      be most practical and informative compared to manometry and scintigraphy in
      predicting treatment success in achalasia patients after therapy.

PMID- 11319069
TI  - Etiology and treatment of achalasia in the pediatric age group.
AB  - Achalasia in children bears many similarities to the disorder in adults, both in
      terms of clinical features and in terms of the approach to therapy. Pharmacologic
      management is of limited temporary benefit until more definitive therapy is
      undertaken. Intrasphincteric injections of botulinum toxin provides safe but
      short-term relief from symptoms. Based on our review of the safety and
      effectiveness of pneumatic dilation, we advocate this procedure as the primary
      form of definitive therapy for achalasia in children. In patients who do not
      achieve satisfactory results from a series of graduated pneumatic dilations,
      Heller myotomy provides safe and effective surgical treatment.

PMID- 11319071
TI  - Risk and surveillance intervals for squamous cell carcinoma in achalasia.
AB  - This article discusses the risk of esophageal squamous cell carcinoma in patients
      with achalasia. A broad review of the literature is provided with incidence and
      prevalence data. Clinical features, pathophysiologic, diagnostic, and prognostic
      aspects are discussed. Information is also provided on how different treatment
      methods impact this disease. Finally, recommendations on surveillance intervals
      are made, based on an evidence-based approach.

PMID- 11319072
TI  - Green fluorescent protein is lighting up fungal biology.

PMID- 11319073
TI  - Microorganisms with a taste for vanilla: microbial ecology of traditional
      Indonesian vanilla curing.
AB  - The microbial ecology of traditional postharvesting processing of vanilla beans
      (curing) was examined using a polyphasic approach consisting of conventional
      cultivation, substrate utilization-based and molecular identification of
      isolates, and cultivation-independent community profiling by 16S ribosomal DNA
      based PCR-denaturing gradient gel electrophoresis. At two different locations, a
      batch of curing beans was monitored. In both batches a major shift in microbial
      communities occurred after short-term scalding of the beans in hot water. Fungi
      and yeast disappeared, although regrowth of fungi occurred in one batch during a
      period in which process conditions were temporarily not optimal. Conventional
      plating showed that microbial communities consisting of thermophilic and
      thermotolerant bacilli (mainly closely related to Bacillus subtilis, B.
      licheniformis, and B. smithii) developed under the high temperatures (up to 65
      degrees C) that were maintained for over a week after scalding. Only small
      changes in the communities of culturable bacteria occurred after this period.
      Molecular analysis revealed that a proportion of the microbial communities could
      not be cultured on conventional agar medium, especially during the high
      temperature period. Large differences between both batches were observed in the
      numbers of microorganisms, in species composition, and in the enzymatic abilities
      of isolated bacteria. These large differences indicate that the effects of
      microbial activities on the development of vanilla flavor could be different for
      each batch of cured vanilla beans.

PMID- 11319074
TI  - Clostridium beijerinckii and Clostridium difficile detoxify methylglyoxal by a
      novel mechanism involving glycerol dehydrogenase.
AB  - In contrast to gram-negative bacteria, little is known about the mechanisms by
      which gram-positive bacteria degrade the toxic metabolic intermediate
      methylglyoxal (MG). Clostridium beijerinckii BR54, a Tn1545 insertion mutant of
      the NCIMB 8052 strain, formed cultures that contained significantly more (free)
      MG than wild-type cultures. Moreover, BR54 was more sensitive to growth
      inhibition by added MG than the wild type, suggesting that it has a reduced
      ability to degrade MG. The single copy of Tn1545 in this strain lies just
      downstream from gldA, encoding glycerol dehydrogenase. As a result of antisense
      RNA production, cell extracts of BR54 possess significantly less glycerol
      dehydrogenase activity than wild-type cell extracts (H. Liyanage, M. Young, and
      E. R. Kashket, J. Mol. Microbiol. Biotechnol. 2:87-93, 2000). Inactivation of
      gldA in both C. beijerinckii and Clostridium difficile gave rise to pinpoint
      colonies that could not be subcultured, indicating that glycerol dehydrogenase
      performs an essential function in both organisms. We propose that this role is
      detoxification of MG. To our knowledge, this is the first report of targeted gene
      disruption in the C. difficile chromosome.

PMID- 11319075
TI  - Characterization of non-starter lactic acid bacteria from Italian ewe cheeses
      based on phenotypic, genotypic, and cell wall protein analyses.
AB  - Non-starter lactic acid bacteria (NSLAB) were isolated from 12 Italian ewe
      cheeses representing six different types of cheese, which in several cases were
      produced by different manufacturers. A total of 400 presumptive Lactobacillus
      isolates were obtained, and 123 isolates and 10 type strains were subjected to
      phenotypic, genetic, and cell wall protein characterization analyses.
      Phenotypically, the cheese isolates included 32% Lactobacillus plantarum
      isolates, 15% L. brevis isolates, 12% L. paracasei subsp. paracasei isolates, 9%
      L. curvatus isolates, 6% L. fermentum isolates, 6% L. casei subsp. casei
      isolates, 5% L. pentosus isolates, 3% L. casei subsp. pseudoplantarum isolates,
      and 1% L. rhamnosus isolates. Eleven percent of the isolates were not
      phenotypically identified. Although a randomly amplified polymorphic DNA (RAPD)
      analysis based on three primers and clustering by the unweighted pair group
      method with arithmetic average (UPGMA) was useful for partially differentiating
      the 10 type strains, it did not provide a species-specific DNA band or a
      combination of bands which permitted complete separation of all the species
      considered. In contrast, sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis cell wall protein profiles clustered by UPGMA were species
      specific and resolved the NSLAB. The only exceptions were isolates phenotypically
      identified as L. plantarum and L. pentosus or as L. casei subsp. casei and L.
      paracasei subsp. paracasei, which were grouped together. Based on protein
      profiles, Italian ewe cheeses frequently contained four different species and 3
      to 16 strains. In general, the cheeses produced from raw ewe milk contained a
      larger number of more diverse strains than the cheeses produced from pasteurized
      milk. The same cheese produced in different factories contained different
      species, as well as strains that belonged to the same species but grouped in
      different RAPD clusters.

PMID- 11319076
TI  - Characterization of the 450-kb linear plasmid in a polychlorinated biphenyl
      degrader, Rhodococcus sp. strain RHA1.
AB  - A strong polychlorinated biphenyl (PCB) degrader, Rhodococcus sp. strain RHA1,
      has diverse biphenyl/PCB degradative genes and harbors huge linear plasmids,
      including pRHL1 (1,100 kb), pRHL2 (450 kb), and pRHL3 (330 kb). The diverse
      degradative genes are distributed mainly on the pRHL1 and pRHL2 plasmids. In this
      study, the structural and functional characteristics of pRHL2 were determined. We
      constructed a physical map of pRHL2, and the degradative enzyme genes, including
      bphB2, etbD2, etbC, bphDEF, bphC2, and bphC4, were localized in three regions.
      Conjugal transfer of pRHL2 between RHA1 mutant derivatives was observed at a
      frequency of 7.5 x 10(-5) transconjugant per recipient. These results suggested
      that the linear plasmid is a possible determinant of propagation of the diverse
      degradative genes in rhodococci. The termini of pRHL2 were cloned and sequenced.
      The left and right termini of pRHL2 had 3-bp perfect terminal inverted repeats
      and were not as similar to each other (64% identity) as the known actinomycete
      linear replicons are. Southern hybridization analysis with pRHL2 terminal probes
      suggested that the right terminus of pRHL2 is similar to pRHL1 and pRHL3 termini.
      Retardation of both terminal fragments in the gel shift assay indicated that each
      terminus of pRHL2 is linked to a protein. We suggest that pRHL2 has invertron
      termini, as has been reported previously for Streptomyces linear replicons.

PMID- 11319077
TI  - Changes in protein synthesis and morphology during acid adaptation of
      Propionibacterium freudenreichii.
AB  - Survival of bacteria in changing environments depends on their ability to adapt
      to abiotic stresses. Microorganisms used in food technology face acid stress
      during fermentation processes. Similarly, probiotic bacteria have to survive acid
      stress imposed within the stomach in order to reach the intestine and play a
      beneficial role. Propionibacteria are used both as cheese starters and as
      probiotics in human alimentation. Adaptation to low pH thus constitutes a limit
      to their efficacy. Acid stress adaptation in the probiotic SI41 strain of
      Propionibacterium freudenreichii was therefore investigated. The acid tolerance
      response (ATR) was evidenced in a chemically defined medium. Transient exposure
      to pH 5 afforded protection toward acid challenge at pH 2. Protein neosynthesis
      was shown to be required for optimal ATR, since chloramphenicol reduced the
      acquired acid tolerance. Important changes in genetic expression were observed
      with two-dimensional electrophoresis during adaptation. Among the up-regulated
      polypeptides, a biotin carboxyl carrier protein and enzymes involved in DNA
      synthesis and repair were identified during the early stress response, while the
      universal chaperonins GroEL and GroES corresponded to a later response. The
      beneficial effect of ATR was evident at both the physiological and morphological
      levels. This study constitutes a first step toward understanding the very
      efficient ATR described in P. freudenreichii.

PMID- 11319078
TI  - Brachyspira (Serpulina) hyodysenteriae gyrB mutants and interstrain transfer of
      coumermycin A(1) resistance.
AB  - To further develop genetic techniques for the enteropathogen Brachyspira
      hyodysenteriae, the gyrB gene of this spirochete was isolated from a lambdaZAPII
      library of strain B204 genomic DNA and sequenced. The putative protein encoded by
      this gene exhibited up to 55% amino acid sequence identity with GyrB proteins of
      various bacterial species, including other spirochetes. B. hyodysenteriae
      coumermycin A(1)-resistant (Cn(r)) mutant strains, both spontaneous and UV
      induced, were isolated by plating B204 cells onto Trypticase soy blood agar
      plates containing 0.5 microg of coumermycin A(1)/ml. The coumermycin A(1) MICs
      were 25 to 100 microg/ml for the resistant strains and 0.1 to 0.25 microg/ml for
      strain B204. Four Cn(r) strains had single nucleotide changes in their gyrB
      genes, corresponding to GyrB amino acid changes of Gly(78) to Ser (two strains),
      Gly(78) to Cys, and Thr(166) to Ala. When Cn(r) strain 435A (Gly(78) to Ser) and
      Cm(r) Km(r) strain SH (DeltaflaA1::cat Deltanox::kan) were cultured together in
      brain heart infusion broth containing 10% (vol/vol) heat-treated (56 degrees C,
      30 min) calf serum, cells resistant to chloramphenicol, coumermycin A(1), and
      kanamycin could be isolated from the cocultures after overnight incubation, but
      such cells could not be isolated from monocultures of either strain. Seven Cn(r)
      Km(r) Cm(r) strains were tested and were determined to have resistance genotypes
      of both strain 435A and strain SH. Cn(r) Km(r) Cm(r) cells could not be isolated
      when antiserum to the bacteriophage-like agent VSH-1 was added to cocultures, and
      the numbers of resistant cells increased fivefold when mitomycin C, an inducer of
      VSH-1 production, was added. These results indicate that coumermycin resistance
      associated with a gyrB mutation is a useful selection marker for monitoring gene
      exchange between B. hyodysenteriae cells. Gene transfer readily occurs between B.
      hyodysenteriae cells in broth culture, a finding with practical importance. VSH-1
      is the likely mechanism for gene transfer.

PMID- 11319080
TI  - Effect of culture conditions on ergosterol as an indicator of biomass in the
      aquatic hyphomycetes.
AB  - Ergosterol is a membrane component specific to fungi that can be used to estimate
      fungal biomass using appropriate factors of conversion. Our objectives were to
      determine the limits of use of ergosterol content as a measure of biomass for
      aquatic hyphomycetes, and to evaluate a previously established ergosterol-to
      biomass conversion factor. We varied inoculum quality, growth medium, and degree
      of shaking of four aquatic hyphomycete species. In cultures inoculated with
      homogenized mycelium, we found a significant effect of shaking condition and
      culture age on ergosterol content. In liquid cultures with defined medium,
      ergosterol content reached 10 to 11 microg/mg of mycelium (dry mass) and varied
      by factors of 2.2 during exponential growth and 1.3 during stationary phase. The
      increase in ergosterol content during exponential phase could be attributed, at
      least in part, to rapid depletion of glucose. Oxygen availability to internal
      hyphae within the mycelial mass is also responsible for the differences found
      between culture conditions. Ergosterol concentration ranged from 0.8 to 1.6
      microg/mg in static cultures inoculated with agar plugs. Ergosterol content
      varied by a factor of 4 in two media of different richnesses. For different
      combinations of these parameters, strong (r(2) = 0.83 to 0.98) and highly
      significant (P << 0.001) linear relationships between ergosterol and mycelial dry
      mass (up to 110 mg) were observed. Overall, the ergosterol content varied by a
      factor of 14 (0.8 to 11 mg/g). These results suggest that care must be taken when
      the ergosterol content is used to compare data generated in different field
      environments.

PMID- 11319079
TI  - Characterization of glycine sarcosine N-methyltransferase and sarcosine
      dimethylglycine N-methyltransferase.
AB  - Glycine betaine is accumulated in cells living in high salt concentrations to
      balance the osmotic pressure. Glycine sarcosine N-methyltransferase (GSMT) and
      sarcosine dimethylglycine N-methyltransferase (SDMT) of Ectothiorhodospira
      halochloris catalyze the threefold methylation of glycine to betaine, with S
      adenosylmethionine acting as the methyl group donor. These methyltransferases
      were expressed in Escherichia coli and purified, and some of their enzymatic
      properties were characterized. Both enzymes had high substrate specificities and
      pH optima near the physiological pH. No evidence of cofactors was found. The
      enzymes showed Michaelis-Menten kinetics for their substrates. The apparent K(m)
      and V(max) values were determined for all substrates when the other substrate was
      present in saturating concentrations. Both enzymes were strongly inhibited by the
      reaction product S-adenosylhomocysteine. Betaine inhibited the methylation
      reactions only at high concentrations.

PMID- 11319081
TI  - Yeast population dynamics during the fermentation and biological aging of sherry
      wines.
AB  - Molecular and physiological analyses were used to study the evolution of the
      yeast population, from alcoholic fermentation to biological aging in the process
      of "fino" sherry wine making. The four races of "flor" Saccharomyces cerevisiae
      (beticus, cheresiensis, montuliensis, and rouxii) exhibited identical restriction
      patterns for the region spanning the internal transcribed spacers 1 and 2 (ITS-1
      and ITS-2) and the 5.8S rRNA gene, but this pattern was different, from those
      exhibited by non-flor S. cerevisiae strains. This flor-specific pattern was
      detected only after wines were fortified, never during alcoholic fermentation,
      and all the strains isolated from the velum exhibited the typical flor yeast
      pattern. By restriction fragment length polymorphism of mitochondrial DNA and
      karyotyping, we showed that (i) the native strain is better adapted to
      fermentation conditions than commercial strains; (ii) two different populations
      of S. cerevisiae strains are involved in the process of elaboration, of fino
      sherry wine, one of which is responsible for must fermentation and the other, for
      wine aging; and (iii) one strain was dominant in the flor population integrating
      the velum from sherry wines produced in Gonzalez Byass wineries, although other
      authors have described a succession of races of flor S. cerevisiae during wine
      aging. Analyzing all these results together, we conclude that yeast population
      dynamics during biological aging is a complex phenomenon and differences between
      yeast populations from different wineries can be observed.

PMID- 11319082
TI  - Sequence analysis of insecticidal genes from Xenorhabdus nematophilus PMFI296.
AB  - Three strains of Xenorhabdus nematophilus showed insecticidal activity when fed
      to Pieris brassicae (cabbage white butterfly) larvae. From one of these strains
      (X. nematophilus PMFI296) a cosmid genome library was prepared in Escherichia
      coli and screened for oral insecticidal activity. Two overlapping cosmid clones
      were shown to encode insecticidal proteins, which had activity when expressed in
      E. coli (50% lethal concentration [LC(50)] of 2 to 6 microg of total protein/g of
      diet). The complete sequence of one cosmid (cHRIM1) was obtained. On cHRIM1, five
      genes (xptA1, -A2, -B1, -C1, and -D1) showed homology with up to 49% identity to
      insecticidal toxins identified in Photorhabdus luminescens, and also a smaller
      gene (chi) showed homology to a putative chitinase gene (38% identity).
      Transposon mutagenesis of the cosmid insert indicated that the genes xptA2,
      xptD1, and chi were not important for the expression of insecticidal activity
      toward P. brassicae. One gene (xptA1) was found to be central for the expression
      of activity, and the genes xptB1 and xptC1 were needed for full activity. The
      location of these genes together on the chromosome and therefore present on a
      single cosmid insert probably accounted for the detection of insecticidal
      activity in this E. coli clone. Although multiple genes may be needed for full
      activity, E. coli cells expressing the xptA1 gene from the bacteriophage lambda
      P(L) promoter were shown to have insecticidal activity (LC(50) of 112 microg of
      total protein/g of diet). This is contrary to the toxin genes identified in P.
      luminescens, which were not insecticidal when expressed individually in E. coli.
      High-level gene expression and the use of a sensitive insect may have aided in
      the detection of insecticidal activity in the E. coli clone expressing xptA1. The
      location of these toxin genes and the chitinase gene and the presence of mobile
      elements (insertion sequence) and tRNA genes on cHRIM1 indicates that this region
      of DNA represents a pathogenicity island on the genome of X. nematophilus
      PMFI296.

PMID- 11319083
TI  - Isoenzyme multiplicity and characterization of recombinant manganese peroxidases
      from Ceriporiopsis subvermispora and Phanerochaete chrysosporium.
AB  - We expressed cDNAs coding for manganese peroxidases (MnPs) from the
      basidiomycetes Ceriporiopsis subvermispora (MnP1) and Phanerochaete chrysosporium
      (H4) under control of the alpha-amylase promoter from Aspergillus oryzae in
      Aspergillus nidulans. The recombinant proteins (rMnP1 and rH4) were expressed at
      similar levels and had molecular masses, both before and after deglycosylation,
      that were the same as those described for the MnPs isolated from the
      corresponding parental strains. Isoelectric focusing (IEF) analysis of rH4
      revealed several isoforms with pIs between 4.83 and 4.06, and one of these pIs
      coincided with the pI described for H4 isolated from P. chrysosporium (pI 4.6).
      IEF of rMnP1 resolved four isoenzymes with pIs between 3.45 and 3.15, and the
      pattern closely resembled the pattern observed with MnPs isolated from C.
      subvermispora grown in solid-state cultures. We compared the abilities of
      recombinant MnPs to use various substrates and found that rH4 could oxidize o
      dianisidine and p-anisidine without externally added manganese, a property not
      previously reported for this MnP isoenzyme from P. chrysosporium.

PMID- 11319084
TI  - Case of localized recombination in 23S rRNA genes from divergent bradyrhizobium
      lineages associated with neotropical legumes.
AB  - Enzyme electrophoresis and rRNA sequencing were used to analyze relationships of
      Bradyrhizobium sp. nodule bacteria from four papilionoid legumes (Clitoria
      javitensis, Erythrina costaricensis, Rhynchosia pyramidalis, and Desmodium
      axillare) growing on Barro Colorado Island (BCI), Panama. Bacteria with identical
      multilocus allele profiles were commonly found in association with two or more
      legume genera. Among the 16 multilocus genotypes (electrophoretic types [ETs])
      detected, six ETs formed a closely related cluster that included isolates from
      all four legume taxa. Bacteria from two other BCI legumes (Platypodium and
      Machaerium) sampled in a previous study were also identical to certain ETs in
      this group. Isolates from different legume genera that had the same ET had
      identical nucleotide sequences for both a 5' portion of the 23S rRNA and the
      nearly full-length 16S rRNA genes. These results suggest that Bradyrhizobium
      genotypes with low host specificity may be prevalent in this tropical forest.
      Parsimony analysis of 16S rRNA sequence variation indicated that most isolates
      were related to Bradyrhizobium japonicum USDA 110, although one ET sampled from
      C. javitensis had a 16S rRNA gene highly similar to that of Bradyrhizobium
      elkanii USDA 76. However, this isolate displayed a mosaic structure within the 5'
      23S rRNA region: one 84-bp segment was identical to that of BCI isolate Pe1-3 (a
      close relative of B. japonicum USDA 110, based on 16S rRNA data), while an
      adjacent 288-bp segment matched that of B. elkanii USDA 76. This mosaic structure
      is one of the first observations suggesting recombination in nature between
      Bradyrhizobium isolates related to B. japonicum versus B. elkanii.

PMID- 11319085
TI  - Genetically controlled self-aggregation of cell-surface-engineered yeast
      responding to glucose concentration.
AB  - We constructed an arming (cell-surface-engineered) yeast displaying two types of
      agglutinin (modified a-agglutinin and alpha-agglutinin) on the cell surface, with
      agglutination being independent of both mating type and pheromones. The modified
      a-agglutinin was artificially prepared by the fusion of the genes encoding Aga1p
      and Aga2p. The modified a-agglutinin could induce agglutination of cells
      displaying Agalpha1p (alpha-agglutinin). The upstream region of the isocitrate
      lyase gene of Candida tropicalis (UPR-ICL), active at a low glucose
      concentration, was used as the promoter to express the modified a-agglutinin- and
      alpha-agglutinin-encoding genes. The arming yeast displaying both agglutinins
      agglutinated and sedimented in response to decreased glucose concentration. When
      the glucose concentration was high, the arming yeast grew normally. In the late
      log phase, when the glucose concentration became very low, agglutination occurred
      suddenly and drastically and yeast cells sedimented completely. Sedimentation was
      confirmed by weighing the aggregated cells after filtration of the broth. Strains
      in which aggregation can be genetically controlled can be used in industrial
      processes in which the separation of yeast cells from the supernatant is
      necessary.

PMID- 11319086
TI  - Induction of laccase activity in Rhizoctonia solani by antagonistic Pseudomonas
      fluorescens strains and a range of chemical treatments.
AB  - Fungi often produce the phenoloxidase enzyme laccase during interactions with
      other organisms, an observation relevant to the development of biocontrols. By
      incorporating the laccase substrate 2,2'-azino-bis(3-ethylbenzthiazoline-6
      sulfonic acid) (ABTS) into agar, we analyzed laccase induction in the plant
      pathogenic fungus Rhizoctonia solani when paired against isolates of the soil
      bacterium Pseudomonas fluorescens. Substantial induction of R. solani laccase was
      seen only in pairings with strains of P. fluorescens known to produce antifungal
      metabolites. To study laccase induction further, a range of chemical treatments
      was applied to R. solani liquid cultures. p-Anisidine, copper(II), manganese(II),
      calcium ionophore A23187, lithium chloride, calcium chloride, cyclic AMP (cAMP),
      caffeine, amphotericin B, paraquat, ethanol, and isopropanol were all found to
      induce laccase; however, the P. fluorescens metabolite viscosinamide did not do
      so at the concentrations tested. The stress caused by these treatments was
      assessed by measuring changes in lipid peroxidation levels and dry weight. The
      results indicated that the laccase induction seen in pairing plate experiments
      was most likely due to calcium or heat shock signaling in response to the effects
      of bacterial metabolites, but that heavy metal and cAMP-driven laccase induction
      was involved in sclerotization.

PMID- 11319087
TI  - Attached and unattached bacterial communities in a 120-meter corehole in an
      acidic, crystalline rock aquifer.
AB  - The bacteria colonizing geologic core sections (attached) were contrasted with
      those found suspended in the groundwater (unattached) by examining the
      microbiology of 16 depth-paired core and groundwater samples using a suite of
      culture-independent and culture-dependent analyses. One hundred twenty-two meters
      was continuously cored from a buried chalcopyrite ore hosted in a biotite-quartz
      monzonite porphyry at the Mineral Park Mine near Kingman, Ariz. Every fourth 1.5
      m core was acquired using microbiologically defensible methods, and these core
      sections were aseptically processed for characterization of the attached
      bacteria. Groundwater samples containing unattached bacteria were collected from
      the uncased corehole at depth intervals corresponding to the individual cores
      using an inflatable straddle packer sampler. The groundwater was acidic (pH 2.8
      to 5.0), with low levels of dissolved oxygen and high concentrations of sulfate
      and metals, including ferrous iron. Total numbers of attached cells were less
      than 10(5) cells g of core material(-1) while unattached cells numbered about
      10(5) cells ml of groundwater(-1). Attached and unattached acidophilic
      heterotrophs were observed throughout the depth profile. In contrast, acidophilic
      chemolithotrophs were not found attached to the rock but were commonly observed
      in the groundwater. Attached communities were composed of low numbers (<40 CFU g(
      1)) of neutrophilic heterotrophs that exhibited a high degree of morphologic
      diversity, while unattached communities contained higher numbers (ca. 10(3) CFU
      ml(-1)) of neutrophilic heterotrophs of limited diversity. Sulfate-reducing
      bacteria were restricted to the deepest samples of both core and groundwater. 16S
      ribosomal DNA sequence analysis of attached, acidophilic isolates indicated that
      organisms closely related to heterotrophic, acidophilic mesophiles such as
      Acidiphilium organovorum and, surprisingly, to the moderately thermophilic
      Alicyclobacillus acidocaldarius were present. The results indicate that viable
      (but possibly inactive) microorganisms were present in the buried ore and that
      there was substantial distinction in biomass and physiological capabilities
      between attached and unattached populations.

PMID- 11319088
TI  - Cytotoxicity associated with trichloroethylene oxidation in Burkholderia cepacia
      G4.
AB  - The effects of trichloroethylene (TCE) oxidation on toluene 2-monooxygenase
      activity, general respiratory activity, and cell culturability were examined in
      the toluene-oxidizing bacterium Burkholderia cepacia G4. Nonspecific damage
      outpaced inactivation of toluene 2-monooxygenase in B. cepacia G4 cells. Cells
      that had degraded approximately 0.5 micromol of TCE (mg of cells(-1)) lost 95% of
      their acetate-dependent O(2) uptake activity (a measure of general respiratory
      activity), yet toluene-dependent O(2) uptake activity decreased only 35%. Cell
      culturability also decreased upon TCE oxidation; however, the extent of loss
      varied greatly (up to 3 orders of magnitude) with the method of assessment.
      Addition of catalase or sodium pyruvate to the surfaces of agar plates increased
      enumeration of TCE-injured cells by as much as 100-fold, indicating that the TCE
      injured cells were ultrasensitive to oxidative stress. Cell suspensions that had
      oxidized TCE recovered the ability to grow in liquid minimal medium containing
      lactate or phenol, but recovery was delayed substantially when TCE degradation
      approached 0.5 micromol (mg of cells(-1)) or 66% of the cells' transformation
      capacity for TCE at the cell density utilized. Furthermore, among B. cepacia G4
      cells isolated on Luria-Bertani agar plates from cultures that had degraded
      approximately 0.5 micromol of TCE (mg of cells(-1)), up to 90% were Tol(-)
      variants, no longer capable of TCE degradation. These results indicate that a
      toxicity threshold for TCE oxidation exists in B. cepacia G4 and that once a cell
      suspension has exceeded this toxicity threshold, the likelihood of reestablishing
      an active, TCE-degrading biomass from the cells will decrease significantly.

PMID- 11319089
TI  - Diversity and specificity of Frankia strains in nodules of sympatric Myrica gale,
      Alnus incana, and Shepherdia canadensis determined by rrs gene polymorphism.
AB  - The identity of Frankia strains from nodules of Myrica gale, Alnus incana subsp.
      rugosa, and Shepherdia canadensis was determined for a natural stand on a lake
      shore sand dune in Wisconsin, where the three actinorhizal plant species were
      growing in close proximity, and from two additional stands with M. gale as the
      sole actinorhizal component. Unisolated strains were compared by their 16S
      ribosomal DNA (rDNA) restriction patterns using a direct PCR amplification
      protocol on nodules. Phylogenetic relationships among nodular Frankia strains
      were analyzed by comparing complete 16S rDNA sequences of study and reference
      strains. Where the three actinorhizal species occurred together, each host
      species was nodulated by a different phylogenetic group of Frankia strains. M.
      gale strains from all three sites belonged to an Alnus-Casuarina group, closely
      related to Frankia alni representative strains, and were low in diversity for a
      host genus considered promiscuous with respect to Frankia microsymbiont genotype.
      Frankia strains from A. incana nodules were also within the Alnus-Casuarina
      cluster, distinct from Frankia strains of M. gale nodules at the mixed
      actinorhizal site but not from Frankia strains from two M. gale nodules at a
      second site in Wisconsin. Frankia strains from nodules of S. canadensis belonged
      to a divergent subset of a cluster of Elaeagnaceae-infective strains and
      exhibited a high degree of diversity. The three closely related local Frankia
      populations in Myrica nodules could be distinguished from one another using our
      approach. In addition to geographic separation and host selectivity for Frankia
      microsymbionts, edaphic factors such as soil moisture and organic matter content,
      which varied among locales, may account for differences in Frankia populations
      found in Myrica nodules.

PMID- 11319090
TI  - Oxygen requirements of the food spoilage yeast Zygosaccharomyces bailii in
      synthetic and complex media.
AB  - Most yeast species can ferment sugars to ethanol, but only a few can grow in the
      complete absence of oxygen. Oxygen availability might, therefore, be a key
      parameter in spoilage of food caused by fermentative yeasts. In this study, the
      oxygen requirement and regulation of alcoholic fermentation were studied in batch
      cultures of the spoilage yeast Zygosaccharomyces bailii at a constant pH, pH 3.0.
      In aerobic, glucose-grown cultures, Z. bailii exhibited aerobic alcoholic
      fermentation similar to that of Saccharomyces cerevisiae and other Crabtree
      positive yeasts. In anaerobic fermentor cultures grown on a synthetic medium
      supplemented with glucose, Tween 80, and ergosterol, S. cerevisiae exhibited
      rapid exponential growth. Growth of Z. bailii under these conditions was
      extremely slow and linear. These linear growth kinetics indicate that cell
      proliferation of Z. bailii in the anaerobic fermentors was limited by a constant,
      low rate of oxygen leakage into the system. Similar results were obtained with
      the facultatively fermentative yeast Candida utilis. When the same experimental
      setup was used for anaerobic cultivation, in complex YPD medium, Z. bailii
      exhibited exponential growth and vigorous fermentation, indicating that a
      nutritional requirement for anaerobic growth was met by complex-medium
      components. Our results demonstrate that restriction of oxygen entry into foods
      and beverages, which are rich in nutrients, is not a promising strategy for
      preventing growth and gas formation by Z. bailii. In contrast to the growth of Z.
      bailii, anaerobic growth of S. cerevisiae on complex YPD medium was much slower
      than growth in synthetic medium, which probably reflected the superior tolerance
      of the former yeast to organic acids at low pH.

PMID- 11319091
TI  - Comparison of logistic regression and linear regression in modeling percentage
      data.
AB  - Percentage is widely used to describe different results in food microbiology,
      e.g., probability of microbial growth, percent inactivated, and percent of
      positive samples. Four sets of percentage data, percent-growth-positive,
      germination extent, probability for one cell to grow, and maximum fraction of
      positive tubes, were obtained from our own experiments and the literature. These
      data were modeled using linear and logistic regression. Five methods were used to
      compare the goodness of fit of the two models: percentage of predictions closer
      to observations, range of the differences (predicted value minus observed value),
      deviation of the model, linear regression between the observed and predicted
      values, and bias and accuracy factors. Logistic regression was a better predictor
      of at least 78% of the observations in all four data sets. In all cases, the
      deviation of logistic models was much smaller. The linear correlation between
      observations and logistic predictions was always stronger. Validation
      (accomplished using part of one data set) also demonstrated that the logistic
      model was more accurate in predicting new data points. Bias and accuracy factors
      were found to be less informative when evaluating models developed for percentage
      data, since neither of these indices can compare predictions at zero. Model
      simplification for the logistic model was demonstrated with one data set. The
      simplified model was as powerful in making predictions as the full linear model,
      and it also gave clearer insight in determining the key experimental factors.

PMID- 11319092
TI  - Export of cytochrome P450 105D1 to the periplasmic space of Escherichia coli.
AB  - CYP105D1, a cytochrome P450 from Streptomyces griseus, was appended at its amino
      terminus to the secretory signal of Escherichia coli alkaline phosphatase and
      placed under the transcriptional control of the native phoA promoter.
      Heterologous expression in E. coli phosphate-limited medium resulted in abundant
      synthesis of recombinant CYP105D1 that was translocated across the bacterial
      inner membrane and processed to yield authentic, heme-incorporated P450 within
      the periplasmic space. Cell extract and whole-cell activity studies showed that
      the periplasmically located CYP105D1 competently catalyzed NADH-dependent
      oxidation of the xenobiotic compounds benzo[a]pyrene and erythromycin, further
      revealing the presence in the E. coli periplasm of endogenous functional redox
      partners. This system offers substantial advantages for the application of P450
      enzymes to whole-cell biotransformation strategies, where the ability of cells to
      take up substrates or discard products may be limited.

PMID- 11319093
TI  - Effects of alkylphosphates and nitrous oxide on microbial degradation of
      polycyclic aromatic hydrocarbons.
AB  - We conducted a series of liquid-culture experiments to begin to evaluate the
      abilities of gaseous sources of nitrogen and phosphorus to support biodegradation
      of polycyclic aromatic hydrocarbons (PAHs). Nutrients examined included nitrous
      oxide, as well as triethylphosphate (TEP) and tributylphosphate (TBP). Cultures
      were established using the indigenous microbial populations from one manufactured
      gas plant (MGP) site and one crude oil-contaminated drilling field site.
      Mineralization of phenanthrene was measured under alternative nutrient regimes
      and was compared to that seen with ammoniacal nitrogen and PO(4). Parallel
      cultures were used to assess removal of a suite of three- to five-ring PAHs. In
      summary, the abilities of the different communities to degrade PAH when
      supplemented with N(2)O, TEP, and TBP were highly variable. For example, in the
      MGP soil, organic P sources, especially TBP, supported a considerably higher
      degree of removal of low-molecular-weight PAHs than did PO(4); however, loss of
      high-molecular-weight compounds was impaired under these conditions. The
      disappearance of most PAHs was significantly less in the oil field soil when
      organophosphates were used. These results indicate that the utility of gaseous
      nutrients for PAH bioremediation in situ may be limited and will very likely have
      to be assessed on a case-by-case basis.

PMID- 11319095
TI  - Comparison of statistical methods for identification of Streptococcus
      thermophilus, Enterococcus faecalis, and Enterococcus faecium from randomly
      amplified polymorphic DNA patterns.
AB  - Thermophilic streptococci play an important role in the manufacture of many
      European cheeses, and a rapid and reliable method for their identification is
      needed. Randomly amplified polymorphic DNA (RAPD) PCR (RAPD-PCR) with two
      different primers coupled to hierarchical cluster analysis has proven to be a
      powerful tool for the classification and typing of Streptococcus thermophilus,
      Enterococcus faecium, and Enterococcus faecalis (G. Moschetti, G. Blaiotta, M.
      Aponte, P. Catzeddu, F. Villani, P. Deiana, and S. Coppola, J. Appl. Microbiol.
      85:25-36, 1998). In order to develop a fast and inexpensive method for the
      identification of thermophilic streptococci, RAPD-PCR patterns were generated
      with a single primer (XD9), and the results were analyzed using artificial neural
      networks (Multilayer Perceptron, Radial Basis Function network, and Bayesian
      network) and multivariate statistical techniques (cluster analysis, linear
      discriminant analysis, and classification trees). Cluster analysis allowed the
      identification of S. thermophilus but not of enterococci. A Bayesian network
      proved to be more effective than a Multilayer Perceptron or a Radial Basis
      Function network for the identification of S. thermophilus, E. faecium, and E.
      faecalis using simplified RAPD-PCR patterns (obtained by summing the bands in
      selected areas of the patterns). The Bayesian network also significantly
      outperformed two multivariate statistical techniques (linear discriminant
      analysis and classification trees) and proved to be less sensitive to the size of
      the training set and more robust in the response to patterns belonging to unknown
      species.

PMID- 11319094
TI  - Predator-specific enrichment of actinobacteria from a cosmopolitan freshwater
      clade in mixed continuous culture.
AB  - We investigated whether individual populations of freshwater bacteria in mixed
      experimental communities may exhibit specific responses to the presence of
      different bacterivorous protists. In two successive experiments, a two-stage
      continuous cultivation system was inoculated with nonaxenic batch cultures of the
      cryptophyte Cryptomonas sp. Algal exudates provided the sole source of organic
      carbon for growth of the accompanying microflora. The dynamics of several 16S
      rRNA-defined bacterial populations were followed in the experimental communities.
      Although the composition and stability of the two microbial communities differed,
      numerous members of the first assemblage could again be detected during the
      second experiment. The introduction of a size-selectively feeding mixotrophic
      nanoflagellate (Ochromonas sp.) always resulted in an immediate bloom of a single
      phylotype population of members of the class Actinobacteria (Ac1). These bacteria
      were phylogenetically affiliated with an uncultured lineage of gram-positive
      bacteria that have been found in freshwater habitats only. The Ac1 cells were
      close to the average size of freshwater bacterioplankton and significantly
      smaller than any of the other experimental community members. In contrast, no
      increase of the Ac1 population was observed in vessels exposed to the
      bacterivorous ciliate Cyclidium glaucoma. However, when the Ochromonas sp. was
      added after the establishment of C. glaucoma, the proportion of population Ac1
      within the microbial community rapidly increased. Populations of a beta
      proteobacterial phylotype related to an Aquabacterium sp. decreased relative to
      the total bacterial communities following the addition of either predator, albeit
      to different extents. The community structure of pelagic microbial assemblages
      can therefore be influenced by the taxonomic composition of the predator
      community.

PMID- 11319096
TI  - Epidemiology of Rhodococcus equi strains on Thoroughbred horse farms.
AB  - Pulsed-field gel electrophoresis of restriction endonuclease-digested genomic DNA
      from a large collection of clinical isolates of Rhodococcus equi, an important
      pathogen of foals, was used to compare strain distribution between farms and over
      time. Forty-four strains were found among 209 isolates, with 5 of these
      accounting for over half the isolates and the 22 strains isolated more than once
      accounting for 90% of the isolates. The average genotypic diversity on each farm
      and in each year was found to be less than the genotypic diversity of the
      isolates taken as a whole, with 5.2% of the total diversity being due to
      differences between farms and 5.5% to differences between years. A small number
      of strains on each farm were found to have caused at least half the clinical
      cases of disease, and these varied between farms and, to a lesser extent, years.
      Most strains were found on more than one farm, and some very similar restriction
      patterns were found among isolates from different continents, indicating that
      strains can be very widespread. Multiple strains were isolated in five of the six
      cases in which more than one isolate from a single foal was examined, indicating
      that disease may commonly be caused by simultaneous infection with multiple
      strains. It was concluded that there are a number of different strains of R. equi
      which carry the vapA gene, and these strains tend to be widespread, but
      individual farms tend to have particular strains associated with them.

PMID- 11319097
TI  - Purification of Synechocystis sp. strain PCC6308 cyanophycin synthetase and its
      characterization with respect to substrate and primer specificity.
AB  - Synechocystis sp. strain PCC6308 cyanophycin synthetase was purified 72-fold in
      three steps by anion exchange chromatography on Q Sepharose, affinity
      chromatography on the triazine dye matrix Procion Blue HE-RD Sepharose, and gel
      filtration on Superdex 200 HR from recombinant cells of Escherichia coli. The
      native enzyme, which catalyzed the incorporation of arginine and aspartic acid
      into cyanophycin, has an apparent molecular mass of 240 +/- 30 kDa and consists
      of identical subunits of 85 +/- 5 kDa. The K(m) values for arginine (49 microM),
      aspartic acid (0.45 mM), and ATP (0.20 mM) indicated that the enzyme had a high
      affinity towards these substrates. During in vitro cyanophycin synthesis, 1.3 +/-
      0.1 mol of ATP per mol of incorporated amino acid was converted to ADP. The
      optima for the enzyme-catalyzed reactions were pH 8.2 and 50 degrees C,
      respectively. Arginine methyl ester (99.5 and 97% inhibition), argininamide (99
      and 96%), S-(2-aminoethyl) cysteine (43 and 42%), beta-hydroxy aspartic acid (35
      and 37%), aspartic acid beta-methyl ester (38 and 40%), norvaline (0 and 3%),
      citrulline (9 and 7%), and asparagine (2 and 0%) exhibited an almost equal
      inhibitory effect on the incorporation of both arginine and aspartic acid,
      respectively, when these compounds were added to the complete reaction mixture.
      In contrast, the incorporation of arginine was diminished to a greater extent
      than that of aspartic acid, respectively, with canavanine (82 and 53%), lysine
      (36 and 19%), agmatine (33 and 25%), D-aspartic acid (37 and 30%), L-glutamic
      acid (13 and 5%), and ornithine (23 and 11%). On the other hand, canavanine (45%
      of maximum activity) and lysine (13%) stimulated the incorporation of aspartic
      acid, whereas aspartic acid beta-methyl ester (53%) and asparagine (9%)
      stimulated the incorporation of arginine. [(3)H]lysine (15% of maximum activity)
      and [(3)H]canavanine (13%) were incorporated into the polymer, when they were
      either used instead of arginine or added to the complete reaction mixture,
      whereas L-glutamic acid was not incorporated. No effect on arginine incorporation
      was obtained by the addition of other amino acids (i.e., alanine, histidine,
      leucine, proline, tryptophan, and glycine). Various samples of chemically
      synthesized poly-alpha,beta-D,L-aspartic acid served as primers for in vitro
      synthesis of cyanophycin, whereas poly-alpha-L-aspartic acid was almost inactive.

PMID- 11319098
TI  - Organization and transcriptional analysis of a six-gene cluster around the rplK
      rplA operon of Corynebacterium glutamicum encoding the ribosomal proteins L11 and
      L1.
AB  - A cluster of six genes, tRNA(Trp)-secE-nusG-rplK-rplA-pkwR, was cloned and
      sequenced from a Corynebacterium glutamicum cosmid library and shown to be
      contiguous in the C. glutamicum genome. These genes encode a tryptophanyl tRNA,
      the protein translocase component SecE, the antiterminator protein NusG, and the
      ribosomal proteins L11 and L1 in addition to PkwR, a putative regulatory protein
      of the LacI-GalR family. S1 nuclease mapping analysis revealed that nusG and rplK
      are expressed as separate transcriptional units and rplK and rplA are
      cotranscribed as a single mRNA. A 19-nucleotide inverted repeat that appears to
      correspond to a transcriptional terminator was located in the 3' region
      downstream from nusG. Northern analysis with different probes confirmed the S1
      mapping results and showed that the secE-rplA four-gene region gives rise to four
      transcripts. secE was transcribed as a 0.5-kb monocistronic mRNA, nusG formed two
      transcripts of 1.4 and 1.0 kb from different initiation sites, and the two
      ribosomal protein genes rplK and rplA were cotranscribed as a single mRNA of 1.6
      kb. A consensus L1 protein binding sequence was identified in the leader region
      of the rplK-rplA transcript, suggesting that expression of the rplK-rplA cluster
      was regulated by autogenous regulation exerted by the L1 protein at the
      translation level. The promoters of the nusG and rplK-rplA genes were subcloned
      in a novel corynebacterial promoter-probe vector and shown to confer strong
      expression of the reporter gene.

PMID- 11319099
TI  - Molecular characterization of an endopolygalacturonase from Fusarium oxysporum
      expressed during early stages of infection.
AB  - The tomato vascular wilt pathogen Fusarium oxysporum f. sp. lycopersici produces
      an array of pectinolytic enzymes that may contribute to penetration and
      colonization of the host plant. Here we report the isolation of pg5, encoding a
      novel extracellular endopolygalacturonase (endoPG) that is highly conserved among
      different formae speciales of F. oxysporum. The putative mature pg5 product has a
      calculated molecular mass of 35 kDa and a pI of 8.3 and is more closely related
      to endoPGs from other fungal plant pathogens than to PG1, the major endoPG of F.
      oxysporum. Overexpression of pg5 in a bacterial heterologous system produced a 35
      kDa protein with endoPG activity. Accumulation of pg5 transcript is induced by
      citrus pectin and D-galacturonic acid and repressed by glucose. As shown by
      reverse transcription-PCR, pg5 is expressed by F. oxysporum in tomato roots
      during the initial stages of infection. Targeted inactivation of pg5 has no
      detectable effect on virulence toward tomato plants.

PMID- 11319100
TI  - Kinetics of methyl t-butyl ether cometabolism at low concentrations by pure
      cultures of butane-degrading bacteria.
AB  - Butane-oxidizing Arthrobacter (ATCC 27778) bacteria were shown to degrade low
      concentrations of methyl t-butyl ether (MTBE; range, 100 to 800 microg/liter)
      with an apparent half-saturation concentration (K(s)) of 2.14 mg/liter and a
      maximum substrate utilization rate (k(c)) of 0.43 mg/mg of total suspended solids
      per day. Arthrobacter bacteria demonstrated MTBE degradation activity when grown
      on butane but not when grown on glucose, butanol, or tryptose phosphate broth.
      The presence of butane, tert-butyl alcohol, or acetylene had a negative impact on
      the MTBE degradation rate. Neither Methylosinus trichosporium OB3b nor
      Streptomyces griseus was able to cometabolize MTBE.

PMID- 11319101
TI  - In vivo regulation of glutamine synthetase activity in the marine chlorophyll b
      containing cyanobacterium Prochlorococcus sp. strain PCC 9511 (oxyphotobacteria).
AB  - The physiological regulation of glutamine synthetase (GS; EC 6.3.1.2) in the
      axenic Prochlorococcus sp. strain PCC 9511 was studied. GS activity and antigen
      concentration were measured using the transferase and biosynthetic assays and the
      electroimmunoassay, respectively. GS activity decreased when cells were subjected
      to nitrogen starvation or cultured with oxidized nitrogen sources, which proved
      to be nonusable for Prochlorococcus growth. The GS activity in cultures subjected
      to long-term phosphorus starvation was lower than that in equivalent nitrogen
      starved cultures. Azaserine, an inhibitor of glutamate synthase, provoked an
      increase in enzymatic activity, suggesting that glutamine is not involved in GS
      regulation. Darkness did not affect GS activity significantly, while the addition
      of diuron provoked GS inactivation. GS protein determination showed that
      azaserine induces an increase in the concentration of the enzyme. The unusual
      responses to darkness and nitrogen starvation could reflect adaptation mechanisms
      of Prochlorococcus for coping with a light- and nutrient-limited environment.

PMID- 11319102
TI  - New pulp biobleaching system involving manganese peroxidase immobilized in a
      silica support with controlled pore sizes.
AB  - Attempts have been made to use manganese peroxidase (MnP) for chlorine-free pulp
      biobleaching, but they have not been commercially viable because of the enzyme's
      low stability. We developed a new pulp biobleaching method involving mesoporous
      material-immobilized manganese peroxidase from Phanerochaete chrysosporium. MnP
      immobilized in FSM-16, a folded-sheet mesoporous material whose pore size is
      nearly the same as the diameter of the enzyme, had the highest thermal stability
      and tolerance to H(2)O(2). MnP immobilized in FSM-16 retained more than 80% of
      its initial activity even after 10 days of continuous reaction. We constructed a
      thermally discontinuous two-stage reactor system, in which the enzyme (39 degrees
      C) and pulp-bleaching (70 degrees C) reactions were performed separately. When
      the treatment of pulp with MnP by means of the two-stage reactor system and
      alkaline extraction was repeated seven times, the brightness of the pulp
      increased to about 88% within 7 h after completion of the last treatment.

PMID- 11319103
TI  - Dissimilatory nitrite reductase genes from autotrophic ammonia-oxidizing
      bacteria.
AB  - The presence of a copper-containing dissimilatory nitrite reductase gene (nirK)
      was discovered in several isolates of beta-subdivision ammonia-oxidizing bacteria
      using PCR and DNA sequencing. PCR primers Cunir3 and Cunir4 were designed based
      on published nirK sequences from denitrifying bacteria and used to amplify a 540
      bp fragment of the nirK gene from Nitrosomonas marina and five additional
      isolates of ammonia-oxidizing bacteria. Amplification products of the expected
      size were cloned and sequenced. Alignment of the nucleic acid and deduced amino
      acid (AA) sequences shows significant similarity (62 to 75% DNA, 58 to 76% AA)
      between nitrite reductases present in these nitrifiers and the copper-containing
      nitrite reductase found in classic heterotrophic denitrifiers. While the presence
      of a nitrite reductase in Nitrosomonas europaea is known from early biochemical
      work, preliminary sequence data from its genome indicate a rather low similarity
      to the denitrifier nirKs. Phylogenetic analysis of the partial nitrifier nirK
      sequences indicates that the topology of the nirK tree corresponds to the 16S
      rRNA and amoA trees. While the role of nitrite reduction in the metabolism of
      nitrifying bacteria is still uncertain, these data show that the nirK gene is
      present in closely related nitrifying isolates from many oceanographic regions
      and suggest that nirK sequences retrieved from the environment may include
      sequences from ammonia-oxidizing bacteria.

PMID- 11319105
TI  - Purification and characterization of two different alpha-L-rhamnosidases, RhaA
      and RhaB, from Aspergillus aculeatus.
AB  - Two proteins exhibiting alpha-L-rhamnosidase activity, RhaA and RhaB, were
      identified upon fractionation and purification of a culture filtrate from
      Aspergillus aculeatus grown on hesperidin. Both proteins were shown to be N
      glycosylated and had molecular masses of 92 and 85 kDa, of which approximately 24
      and 15%, respectively, were contributed by carbohydrate. RhaA and RhaB, optimally
      active at pH 4.5 to 5, showed K(m) and V(max) values of 2.8 mM and 24 U/mg (RhaA)
      and 0.30 mM and 14 U/mg (RhaB) when tested for p-nitrophenyl-alpha-L
      rhamnopyranoside. Both enzymes were able to hydrolyze alpha-1,2 and alpha-1,6
      linkages to beta-D-glucosides. Using polyclonal antibodies, the corresponding
      cDNA of both alpha-L-rhamnosidases, rhaA and rhaB, was cloned. On the basis of
      the amino acid sequences derived from the cDNA clones, both proteins are highly
      homologous (60% identity).

PMID- 11319104
TI  - Mycobacterium diversity and pyrene mineralization in petroleum-contaminated
      soils.
AB  - Degradative strains of fast-growing Mycobacterium spp. are commonly isolated from
      polycyclic aromatic hydrocarbon (PAH)-contaminated soils. Little is known,
      however, about the ecology and diversity of indigenous populations of these fast
      growing mycobacteria in contaminated environments. In the present study 16S rRNA
      genes were PCR amplified using Mycobacterium-specific primers and separated by
      temperature gradient gel electrophoresis (TGGE), and prominent bands were
      sequenced to compare the indigenous Mycobacterium community structures in four
      pairs of soil samples taken from heavily contaminated and less contaminated areas
      at four different sites. Overall, TGGE profiles obtained from heavily
      contaminated soils were less diverse than those from less contaminated soils.
      This decrease in diversity may be due to toxicity, since significantly fewer
      Mycobacterium phylotypes were detected in soils determined to be toxic by the
      Microtox assay than in nontoxic soils. Sequencing and phylogenetic analysis of
      prominent TGGE bands indicated that novel strains dominated the soil
      Mycobacterium community. Mineralization studies using [(14)C]pyrene added to four
      petroleum-contaminated soils, with and without the addition of the known pyrene
      degrader Mycobacterium sp. strain RJGII-135, indicated that inoculation increased
      the level of degradation in three of the four soils. Mineralization results
      obtained from a sterilized soil inoculated with strain RJGII-135 suggested that
      competition with indigenous microorganisms may be a significant factor affecting
      biodegradation of PAHs. Pyrene-amended soils, with and without inoculation with
      strain RJGII-135, experienced both increases and decreases in the population
      sizes of the inoculated strain and indigenous Mycobacterium populations during
      incubation.

PMID- 11319106
TI  - Detection of the bacteriocin propionicin PLG-1 with polyvalent anti-PLG-1
      antiserum.
AB  - Polyclonal antibodies against the bacteriocin propionicin PLG-1 were produced in
      rabbits at high titer (256,000 to 512,000, as determined by indirect enzyme
      linked immunosorbent assay [ELISA]). Anti-PLG-1 antiserum neutralized the
      antimicrobial activity of PLG-1 preparations in a well diffusion assay. Cross
      reacting protein was detected using an indirect ELISA of the culture supernatant
      from a fed-batch fermentation of the producer strain Propionibacterium thoenii
      P127 within the first 24 h of incubation, but bacteriocin activity was not
      detected in the same culture until 217 h of incubation. Culture supernatants from
      156 strains of classical dairy propionibacteria were tested by indirect ELISA at
      5 and 12 days of incubation for production of cross-reacting protein and by well
      diffusion assay for bacteriocin activity. Cross-reacting protein was detected in
      52 strains: all of the tested strains of P. thoenii, most of the strains of
      Propionibacterium jensenii, and a minority of the Propionibacterium
      acidipropionici and Propionibacterium freudenreichii strains. Of these 52
      strains, only 4 strains of P. thoenii showed bacteriocin activity in a well
      diffusion assay. Eight bacteriocin-negative mutants of strain P127 were negative
      in both ELISA and well diffusion assays. Western blot analysis showed that three
      protein bands bound anti-PLG-1 antibodies in culture supernatants: a 9.1-kDa band
      that is assumed to be the PLG-1 monomer and 16.2- and 27.5-kDa bands that may be
      precursors, multimers, or complexes of PLG-1.

PMID- 11319107
TI  - Morphological and physiological characterization of Listeria monocytogenes
      subjected to high hydrostatic pressure.
AB  - High hydrostatic pressure is a new food preservation technology known for its
      capacity to inactivate spoilage and pathogenic microorganisms. That inactivation
      is usually assessed by the number of colonies growing on solid media after
      treatment. Under normal conditions the method does not permit recovery of damaged
      cells and may underestimate the number of cells that will remain viable and grow
      after a few days in high-pressure-processed foodstuffs. This study investigated
      the damage inflicted on Listeria monocytogenes cells treated by high pressure for
      10 min at 400 MPa in pH 5.6 citrate buffer. Under these conditions, no cell
      growth occurred after 48 h on plate count agar. Scanning electron microscopy,
      light scattering by flow cytometry, and cell volume measurements were compared to
      evaluate the morphological changes in cells after pressurization. All these
      methods revealed that cellular morphology was not really affected. Esterase
      activity, as assessed either by enzymatic activity assays or by carboxy
      fluorescein diacetate fluorescence monitored by flow cytometry, was dramatically
      lowered, but not totally obliterated, under the effects of treatment. The
      measurement of propidium iodide uptake followed by flow cytometry demonstrated
      that membrane integrity was preserved in a small part of the population, although
      the membrane potential measured by analytical methods or evaluated by oxonol
      uptake was reduced from -86 to -5 mV. These results showed that such combined
      methods as fluorescent dyes monitored by flow cytometry and physiological
      activity measurements provide valuable indications of cellular viability.

PMID- 11319108
TI  - Survival of Campylobacter jejuni during stationary phase: evidence for the
      absence of a phenotypic stationary-phase response.
AB  - When Campylobacter jejuni NCTC 11351 was grown microaerobically in rich medium at
      39 degrees C, entry into stationary phase was followed by a rapid decline in
      viable numbers to leave a residual population of 1% of the maximum number or
      less. Loss of viability was preceded by sublethal injury, which was seen as a
      loss of the ability to grow on media containing 0.1% sodium deoxycholate or 1%
      sodium chloride. Resistance of cells to mild heat stress (50 degrees C) or
      aeration was greatest in exponential phase and declined during early stationary
      phase. These results show that C. jejuni does not mount the normal phenotypic
      stationary-phase response which results in enhanced stress resistance. This
      conclusion is consistent with the absence of rpoS homologues in the recently
      reported genome sequence of this species and their probable absence from strain
      NCTC 11351. During prolonged incubation of C. jejuni NCTC 11351 in stationary
      phase, an unusual pattern of decreasing and increasing heat resistance was
      observed that coincided with fluctuations in the viable count. During stationary
      phase of Campylobacter coli UA585, nonmotile variants and those with impaired
      ability to form coccoid cells were isolated at high frequency. Taken together,
      these observations suggest that stationary-phase cultures of campylobacters are
      dynamic populations and that this may be a strategy to promote survival in at
      least some strains. Investigation of two spontaneously arising variants (NM3 and
      SC4) of C. coli UA585 showed that a reduced ability to form coccoid cells did not
      affect survival under nongrowth conditions.

PMID- 11319109
TI  - Comparison of nifH gene pools in soils and soil microenvironments with
      contrasting properties.
AB  - The similarities and differences in the structures of the nifH gene pools of six
      different soils (Montrond, LCSA-p, Vernon, Dombes, LCSA-c, and Thysse Kaymor) and
      five soil fractions extracted from LCSA-c were studied. Bacterial DNA was
      directly extracted from the soils, and a region of the nifH gene was amplified by
      PCR and analyzed by restriction. Soils were selected on the basis of differences
      in soil management, plant cover, and major physicochemical properties.
      Microenvironments differed on the basis of the sizes of the constituent particles
      and the organic carbon and clay contents. Restriction profiles were subjected to
      principal-component analysis. We showed that the composition of the diazotrophic
      communities varied both on a large scale (among soils) and on a microscale (among
      microenvironments in LCSA-c soil). Soil management seemed to be the major
      parameter influencing differences in the nifH gene pool structure among soils by
      controlling inorganic nitrogen content and its variation. However,
      physicochemical parameters (texture and total C and N contents) were found to
      correlate with differences among nifH gene pools on a microscale. We hypothesize
      that the observed nifH genetic structures resulted from the adaptation to
      fluctuating conditions (cultivated soil, forest soil, coarse fractions) or
      constant conditions (permanent pasture soil, fine fractions). We attempted to
      identify a specific band within the profile of the clay fraction by cloning and
      sequencing it and comparing it with the gene databases. Unexpectedly, the nifH
      sequences of the dominant bacteria were most similar to sequences of unidentified
      marine eubacteria.

PMID- 11319110
TI  - Stable transformation of the Xylella fastidiosa citrus variegated chlorosis
      strain with oriC plasmids.
AB  - Xylella fastidiosa is a gram-negative, xylem-limited bacterium affecting
      economically important crops (e.g., grapevine, citrus, and coffee). The citrus
      variegated chlorosis (CVC) strain of X. fastidiosa is the causal agent of this
      severe disease of citrus in Brazil and represents the first plant-pathogenic
      bacterium for which the genome sequence was determined. Plasmids for the CVC
      strain of X. fastidiosa were constructed by combining the chromosomal replication
      origin (oriC) of X. fastidiosa with a gene which confers resistance to kanamycin
      (Kan(r)). In plasmid p16KdAori, the oriC fragment comprised the dnaA gene as well
      as the two flanking intergenic regions, whereas in plasmid p16Kori the oriC
      fragment was restricted to the dnaA-dnaN intergenic region, which contains dnaA
      box like sequences and AT-rich clusters. In plasmid p16K, no oriC sequence was
      present. In the three constructs, the promoter region of one of the two X.
      fastidiosa rRNA operons was used to drive the transcription of the Kan(r) gene to
      optimize the expression of kanamycin resistance in X. fastidiosa. Five CVC X.
      fastidiosa strains, including strain 9a5c, the genome sequence of which was
      determined, and two strains isolated from coffee, were electroporated with
      plasmid p16KdAori or p16Kori. Two CVC isolates, strains J1a12 and B111, yielded
      kanamycin-resistant transformants when electroporated with plasmid p16KdAori or
      p16Kori but not when electroporated with p16K. Southern blot analyses of total
      DNA extracted from the transformants revealed that, in all clones tested, the
      plasmid had integrated into the host chromosome at the promoter region of the
      rRNA operon by homologous recombination. To our knowledge, this is the first
      report of stable transformation in X. fastidiosa. Integration of oriC plasmids
      into the X. fastidiosa chromosome by homologous recombination holds considerable
      promise for functional genomics by specific gene inactivation.

PMID- 11319111
TI  - Degradation of substituted phenylurea herbicides by Arthrobacter globiformis
      strain D47 and characterization of a plasmid-associated hydrolase gene, puhA.
AB  - Arthrobacter globiformis D47 was shown to degrade a range of substituted
      phenylurea herbicides in soil. This strain contained two plasmids of
      approximately 47 kb (pHRIM620) and 34 kb (pHRIM621). Plasmid-curing experiments
      produced plasmid-free strains as well as strains containing either the 47- or the
      34-kb plasmid. The strains were tested for their ability to degrade diuron, which
      demonstrated that the degradative genes were located on the 47-kb plasmid.
      Studies on the growth of these strains indicated that the ability to degrade
      diuron did not offer a selective advantage to A. globiformis D47 on minimal
      medium designed to contain the herbicide as a sole carbon source. The location of
      the genes on a plasmid and a lack of selection would explain why the degradative
      phenotype, as with many other pesticide-degrading bacteria, can be lost on
      subculture. A 22-kb EcoRI fragment of plasmid pHRIM620 was expressed in
      Escherichia coli and enabled cells to degrade diuron. Transposon mutagenesis of
      this fragment identified one open reading frame that was essential for enzyme
      activity. A smaller subclone of this gene (2.5 kb) expressed in E. coli coded for
      the protein that degraded diuron. This gene and its predicted protein sequence
      showed only a low level of protein identity (25% over ca. 440 amino acids) to
      other database sequences and was named after the enzyme it encoded, phenylurea
      hydrolase (puhA gene).

PMID- 11319112
TI  - Intra- and extracellular beta-galactosidases from Bifidobacterium bifidum and B.
      infantis: molecular cloning, heterologous expression, and comparative
      characterization.
AB  - Three beta-galactosidase genes from Bifidobacterium bifidum DSM20215 and one beta
      galactosidase gene from Bifidobacterium infantis DSM20088 were isolated and
      characterized. The three B. bifidum beta-galactosidases exhibited a low degree of
      amino acid sequence similarity to each other and to previously published beta
      galactosidases classified as family 2 glycosyl hydrolases. Likewise, the B.
      infantis beta-galactosidase was distantly related to enzymes classified as family
      42 glycosyl hydrolases. One of the enzymes from B. bifidum, termed BIF3, is most
      probably an extracellular enzyme, since it contained a signal sequence which was
      cleaved off during heterologous expression of the enzyme in Escherichia coli.
      Other exceptional features of the BIF3 beta-galactosidase were (i) the monomeric
      structure of the active enzyme, comprising 1,752 amino acid residues (188 kDa)
      and (ii) the molecular organization into an N-terminal beta-galactosidase domain
      and a C-terminal galactose binding domain. The other two B. bifidum beta
      galactosidases and the enzyme from B. infantis were multimeric, intracellular
      enzymes with molecular masses similar to typical family 2 and family 42 glycosyl
      hydrolases, respectively. Despite the differences in size, molecular composition,
      and amino acid sequence, all four beta-galactosidases were highly specific for
      hydrolysis of beta-D-galactosidic linkages, and all four enzymes were able to
      transgalactosylate with lactose as a substrate.

PMID- 11319113
TI  - Diversity and seasonal fluctuations of the dominant members of the bacterial soil
      community in a wheat field as determined by cultivation and molecular methods.
AB  - There is a paucity of knowledge on microbial community diversity and naturally
      occurring seasonal variations in agricultural soil. For this purpose the soil
      microbial community of a wheat field on an experimental farm in The Netherlands
      was studied by using both cultivation-based and molecule-based methods. Samples
      were taken in the different seasons over a 1-year period. Fatty acid-based typing
      of bacterial isolates obtained via plating revealed a diverse community of mainly
      gram-positive bacteria, and only a few isolates appeared to belong to the
      Proteobacteria and green sulfur bacteria. Some genera, such as Micrococcus,
      Arthrobacter, and Corynebacterium were detected throughout the year, while
      Bacillus was found only in July. Isolate diversity was lowest in July, and the
      most abundant species, Arthrobacter oxydans, and members of the genus Pseudomonas
      were found in reduced numbers in July. Analysis by molecular techniques showed
      that diversity of cloned 16S ribosomal DNA (rDNA) sequences was greater than the
      diversity among cultured isolates. Moreover, based on analysis of 16S rDNA
      sequences, there was a more even distribution among five main divisions,
      Acidobacterium, Proteobacteria, Nitrospira, cyanobacteria, and green sulfur
      bacteria. No clones were found belonging to the gram-positive bacteria, which
      dominated the cultured isolates. Seasonal fluctuations were assessed by
      denaturing gradient gel electrophoresis. Statistical analysis of the banding
      patterns revealed significant differences between samples taken in different
      seasons. Cluster analysis of the patterns revealed that the bacterial community
      in July clearly differed from those in the other months. Although the molecule-
      and cultivation-based methods allowed the detection of different parts of the
      bacterial community, results from both methods indicated that the community
      present in July showed the largest difference from the communities of the other
      months. Efforts were made to use the sequence data for providing insight into
      more general ecological relationships. Based on the distribution of 16S rDNA
      sequences among the bacterial divisions found in this work and in literature, it
      is suggested that the ratio between the number of Proteobacteria and
      Acidobacterium organisms might be indicative of the trophic level of the soil.

PMID- 11319114
TI  - Applications of gene replacement technology to Streptomyces clavuligerus strain
      development for clavulanic acid production.
AB  - Cephamycin C production was blocked in wild-type cultures of the clavulanic acid
      producing organism Streptomyces clavuligerus by targeted disruption of the gene
      (lat) encoding lysine epsilon-aminotransferase. Specific production of clavulanic
      acid increased in the lat mutants derived from the wild-type strain by 2- to 2.5
      fold. Similar beneficial effects on clavulanic acid production were noted in
      previous studies when gene disruption was used to block the production of the non
      clavulanic acid clavams produced by S. clavuligerus. Therefore, mutations in lat
      and in cvm1, a gene involved in clavam production, were introduced into a high
      titer industrial strain of S. clavuligerus to create a double mutant with defects
      in production of both cephamycin C and clavams. Production of both cephamycin C
      and non-clavulanic acid clavams was eliminated in the double mutant, and
      clavulanic acid titers increased about 10% relative to those of the parental
      strain. This represents the first report of the successful use of genetic
      engineering to eliminate undesirable metabolic pathways in an industrial strain
      used for the production of an antibiotic important in human medicine.

PMID- 11319115
TI  - The cel4 gene of Agaricus bisporus encodes a beta-mannanase.
AB  - Mannases have industrial uses in food and pulp industries, and their regulation
      may influence development of the mushrooms of commercially important
      basidiomycetes. We expressed an Agaricus bisporus cel4 cDNA, which encodes a
      mannanase, in Saccharomyces cerevisiae and Pichia pastoris. CEL4 had no
      detectable activity on cellulose or xylan. This gene is the first isolated from
      this economically important fungus to encode a mannanase. P. pastoris secreted
      about three times more CEL4 than S. cerevisiae. The removal of the cellulose
      binding domain of CEL4 lowered the secreted specific activity by P. pastoris by
      approximately 97%. The genomic sequence of cel4 was isolated by screening a
      cosmid library of A. bisporus C54-carb8. The open reading frame was interrupted
      by 12 introns. The level of extracellular CEL4 increases dramatically at the
      postharvest stage in compost extracts of A. bisporus fruiting cultures. In
      laboratory liquid cultures of A. bisporus, the activity of CEL4 detected in the
      culture filtrate reached a maximum after 21 days. The levels of CEL4 broadly
      mirrored the levels of enzyme activity. In the Solka floc-bound mycelium, CEL4
      protein showed a maximum after 2 to 3 weeks of culture and then declined. Changes
      in CEL4 activity during fruiting-body development suggest that hemicellulose
      utilization plays an important role in sporophore formation. The availability of
      the cloned gene will further studies of compost decomposition and the
      extracellular enzymes that fungi deploy in this process.

PMID- 11319116
TI  - Stress and stress-induced neuroendocrine changes increase the susceptibility of
      juvenile oysters (Crassostrea gigas) to Vibrio splendidus.
AB  - Oysters are permanently exposed to various microbes, and their defense system is
      continuously solicited to prevent accumulation of invading and pathogenic
      organisms. Therefore, impairment of the animal's defense system usually results
      in mass mortalities in cultured oyster stocks or increased bacterial loads in
      food products intended for human consumption. In the present study, experiments
      were conducted to examine the effects of stress on the juvenile oyster's
      resistance to the oyster pathogen Vibrio splendidus. Oysters (Crassostrea gigas)
      were challenged with a low dose of a pathogenic V. splendidus strain and
      subjected to a mechanical stress 3 days later. Both mortality and V. splendidus
      loads increased in stressed oysters, whereas they remained low in unstressed
      animals. Injection of noradrenaline or adrenocorticotropic hormone, two key
      components of the oyster neuroendocrine stress response system, also caused
      higher mortality and increased accumulation of V. splendidus in challenged
      oysters. These results suggest that the physiological changes imposed by stress,
      or stress hormones, influenced host-pathogen interactions in oysters and
      increased juvenile C. gigas vulnerability to Vibrio splendidus.

PMID- 11319117
TI  - Development and validation of corynebacterium DNA microarrays.
AB  - We have developed DNA microarray techniques for studying Corynebacterium
      glutamicum. A set of 52 C. glutamicum genes encoding enzymes from primary
      metabolism was amplified by PCR and printed in triplicate onto glass slides.
      Total RNA was extracted from cells harvested during the exponential-growth and
      lysine production phases of a C. glutamicum fermentation. Fluorescently labeled
      cDNAs were prepared by reverse transcription using random hexamer primers and
      hybridized to the microarrays. To establish a set of benchmark metrics for this
      technique, we compared the variability between replicate spots on the same slide,
      between slides hybridized with cDNAs from the same labeling reaction, and between
      slides hybridized with cDNAs prepared in separate labeling reactions. We found
      that the results were both robust and statistically reproducible. Spot-to-spot
      variability was 3.8% between replicate spots on a given slide, 5.0% between spots
      on separate slides (though hybridized with identical, labeled cDNA), and 8.1%
      between spots from separate slides hybridized with samples from separate reverse
      transcription reactions yielding an average spot to spot variability of 7.1%
      across all conditions. Furthermore, when we examined the changes in gene
      expression that occurred between the two phases of the fermentation, we found
      that results for the majority of the genes agreed with observations made using
      other methods. These procedures will be a valuable addition to the metabolic
      engineering toolbox for the improvement of C. glutamicum amino acid-producing
      strains.

PMID- 11319118
TI  - Shewanella putrefaciens adhesion and biofilm formation on food processing
      surfaces.
AB  - Laboratory model systems were developed for studying Shewanella putrefaciens
      adhesion and biofilm formation under batch and flow conditions. S. putrefaciens
      plays a major role in food spoilage and may cause microbially induced corrosion
      on steel surfaces. S. putrefaciens bacteria suspended in buffer adhered readily
      to stainless steel surfaces. Maximum numbers of adherent bacteria per square
      centimeter were reached in 8 h at 25 degrees C and reflected the cell density in
      suspension. Numbers of adhering bacteria from a suspension containing 10(8)
      CFU/ml were much lower in a laminar flow system (modified Robbins device)
      (reaching 10(2) CFU/cm(2)) than in a batch system (reaching 10(7) CFU/cm(2)), and
      maximum numbers were reached after 24 h. When nutrients were supplied, S.
      putrefaciens grew in biofilms with layers of bacteria. The rate of biofilm
      formation and the thickness of the film were not dependent on the availability of
      carbohydrate (lactate or glucose) or on iron starvation. The number of S.
      putrefaciens bacteria on the surface was partly influenced by the presence of
      other bacteria (Pseudomonas fluorescens) which reduced the numbers of S.
      putrefaciens bacteria in the biofilm. Numbers of bacteria on the surface must be
      quantified to evaluate the influence of environmental factors on adhesion and
      biofilm formation. We used a combination of fluorescence microscopy (4',6'
      diamidino-2-phenylindole staining and in situ hybridization, for mixed-culture
      studies), ultrasonic removal of bacteria from surfaces, and indirect
      conductometry and found this combination sufficient to quantify bacteria on
      surfaces.

PMID- 11319119
TI  - Flow cytometric assessment of viability of lactic acid bacteria.
AB  - The viability of lactic acid bacteria is crucial for their applications as dairy
      starters and as probiotics. We investigated the usefulness of flow cytometry
      (FCM) for viability assessment of lactic acid bacteria. The esterase substrate
      carboxyfluorescein diacetate (cFDA) and the dye exclusion DNA binding probes
      propidium iodide (PI) and TOTO-1 were tested for live/dead discrimination using a
      Lactococcus, a Streptococcus, three Lactobacillus, two Leuconostoc, an
      Enterococcus, and a Pediococcus species. Plate count experiments were performed
      to validate the results of the FCM assays. The results showed that cFDA was an
      accurate stain for live cells; in exponential-phase cultures almost all cells
      were labeled, while 70 degrees C heat-killed cultures were left unstained. PI did
      not give clear live/dead discrimination for some of the species. TOTO-1, on the
      other hand, gave clear discrimination between live and dead cells. The
      combination of cFDA and TOTO-1 gave the best results. Well-separated
      subpopulations of live and dead cells could be detected with FCM. Cell sorting of
      the subpopulations and subsequent plating on agar medium provided direct evidence
      that cFDA labels the culturable subpopulation and that TOTO-1 labels the
      nonculturable subpopulation. Applied to cultures exposed to deconjugated bile
      salts or to acid, cFDA and TOTO-1 proved to be accurate indicators of
      culturability. Our experiments with lactic acid bacteria demonstrated that the
      combination of cFDA and TOTO-1 makes an excellent live/dead assay with versatile
      applications.

PMID- 11319120
TI  - Natural communities of novel archaea and bacteria growing in cold sulfurous
      springs with a string-of-pearls-like morphology.
AB  - We report the identification of novel archaea living in close association with
      bacteria in the cold (approximately 10 degrees C) sulfurous marsh water of the
      Sippenauer Moor near Regensburg, Bavaria, Germany. These microorganisms form a
      characteristic, macroscopically visible structure, morphologically comparable to
      a string of pearls. Tiny, whitish globules (the pearls; diameter, about 0.5 to
      3.0 mm) are connected to each other by thin, white-colored threads. Fluorescent
      in situ hybridization (FISH) studies have revealed that the outer part of the
      pearls is mainly composed of bacteria, with a filamentous bacterium
      predominating. Internally, archaeal cocci are the predominant microorganisms,
      with up to 10(7) cells estimated to be present in a single pearl. The archaea
      appear to be embedded in a polymer of unknown chemical composition. According to
      FISH and 16S rRNA gene sequence analysis, the archaea are affiliated with the
      euryarchaeal kingdom. The new euryarchaeal sequence represents a deep
      phylogenetic branch within the 16S rRNA tree and does not show extensive
      similarity to any cultivated archaea or to 16S rRNA gene sequences from
      environmental samples.

PMID- 11319121
TI  - Biotransformations of paralytic shellfish toxins by bacteria isolated from
      bivalve molluscs.
AB  - Due to the possibility that bacteria could be involved in the clearance of
      paralytic shellfish toxins (PST) from bivalve molluscs, investigations into
      which, if any, bacteria were able to grow at the expense of PST focused on
      several common shellfish species. These species were blue mussels, oysters, razor
      fish, cockles, and queen and king scallops. Bacteria associated with these
      shellfish were isolated on marine agar 2216 and characterized by their carbon
      utilization profiles (BIOLOG). Selected isolates from groups demonstrating 90%
      similarity were screened for their ability to metabolize a range of PST
      (gonyautoxins 1 and 4 [GTX 1/4], GTX 2/3, GTX 5, saxitoxin, and neosaxitoxin)
      using a novel screening method and confirming its results by high-performance
      liquid chromatography. Results suggest that molluscan bacteria have different
      capacities to utilize and transform PST analogues. For example, isolates M12 and
      R65 were able to reductively transform GTX 1/4 with concomitant production of GTX
      2/3, while isolate Q5 apparently degraded GTX 1/4 without the appearance of other
      GTXs. Other observed possible mechanisms of PST transformations include
      decarbamoylation by isolate M12 and sulfation of GTXs by isolates Q5, R65, M12,
      and C3. These findings raise questions as to the possible role of bacteria
      resident in the shellfish food transport system. Some researchers have suggested
      that the microflora play a role in supplying nutritional requirements of the
      host. This study demonstrates that bacteria may also be involved in PST
      transformation and elimination in molluscan species.

PMID- 11319122
TI  - DNA extraction from soils: old bias for new microbial diversity analysis methods.
AB  - The impact of three different soil DNA extraction methods on bacterial diversity
      was evaluated using PCR-based 16S ribosomal DNA analysis. DNA extracted directly
      from three soils showing contrasting physicochemical properties was subjected to
      amplified ribosomal DNA restriction analysis and ribosomal intergenic spacer
      analysis (RISA). The obtained RISA patterns revealed clearly that both the
      phylotype abundance and the composition of the indigenous bacterial community are
      dependent on the DNA recovery method used. In addition, this effect was also
      shown in the context of an experimental study aiming to estimate the impact on
      soil biodiversity of the application of farmyard manure or sewage sludge onto a
      monoculture of maize for 15 years.

PMID- 11319123
TI  - Differentiation of environmental and clinical isolates of Vibrio mimicus from
      Vibrio cholerae by multilocus enzyme electrophoresis.
AB  - In this study, we demonstrated that analyzed strains of Vibrio mimicus and Vibrio
      cholerae could be separated in two groups by using multilocus enzyme
      electrophoresis (MEE) data from 14 loci. We also showed that the combination of
      four enzymatic loci enables us to differentiate these two species. Our results
      showed that the ribosomal intergenic spacer regions PCR-mediated identification
      system failed, in some cases, to differentiate between V. mimicus and V.
      cholerae. On the other hand, MEE proved to be a powerful molecular tool for the
      discrimination of these two species even when atypical strains were analyzed.

PMID- 11319124
TI  - Zeamatin inhibits trypsin and alpha-amylase activities.
AB  - Zeamatin is a 22-kDa protein isolated from Zea mays that has antifungal activity
      against human and plant pathogens. Unlike other pathogenesis-related group 5
      proteins, zeamatin inhibits insect alpha-amylase and mammalian trypsin
      activities. It is of clinical significance that zeamatin did not inhibit human
      alpha-amylase activity and inhibited mammalian trypsin activity only at high
      molar concentrations.

PMID- 11319125
TI  - Mutations in the csgD promoter associated with variations in curli expression in
      certain strains of Escherichia coli O157:H7.
AB  - Single-base-pair csgD promoter mutations in human outbreak Escherichia coli
      O157:H7 strains ATCC 43894 and ATCC 43895 coincided with differential Congo red
      dye binding from curli fiber expression. Red phenotype csgD::lacZ promoter
      fusions had fourfold-greater expression than white promoter fusions. Cloning the
      red variant csgDEFG operon into white variants induced the red phenotype.
      Substrate utilization differed between red and white variants.

PMID- 11319126
TI  - 2-Bromoethanesulfonate affects bacteria in a trichloroethene-dechlorinating
      culture.
AB  - Long-term exposure to 2-bromoethanesulfonate (BES), an agent known to inhibit
      methanogenesis, altered the bacterial community structure of an anaerobic
      enrichment culture that reductively dechlorinated trichloroethene (TCE). BES did
      not hinder the dechlorination of TCE or other chlorinated ethenes as previously
      reported, although different intermediates and end products were observed.

PMID- 11319127
TI  - 16S ribosomal DNA characterization of nitrogen-fixing bacteria isolated from
      banana (Musa spp.) and pineapple (Ananas comosus (L.) Merril).
AB  - Nitrogen-fixing bacteria isolated from banana (Musa spp.) and pineapple (Ananas
      comosus (L.) Merril) were characterized by amplified 16S ribosomal DNA
      restriction analysis and 16S rRNA sequence analysis. Herbaspirillum seropedicae,
      Herbaspirillum rubrisubalbicans, Burkholderia brasilensis, and Burkholderia
      tropicalis were identified. Eight other types were placed in close proximity to
      these genera and other alpha and beta Proteobacteria.

PMID- 11319128
TI  - The celA gene, encoding a glycosyl hydrolase family 3 beta-glucosidase in
      Azospirillum irakense, is required for optimal growth on cellobiosides.
AB  - The CelA beta-glucosidase of Azospirillum irakense, belonging to glycosyl
      hydrolase family 3 (GHF3), preferentially hydrolyzes cellobiose and releases
      glucose units from the C(3), C(4), and C(5) oligosaccharides. The growth of a
      DeltacelA mutant on these cellobiosides was affected. In A. irakense, the GHF3
      beta-glucosidases appear to be functional alternatives for the GHF1 beta
      glucosidases in the assimilation of beta-glucosides by other bacteria.

PMID- 11319129
TI  - Detection of acute bee paralysis virus and black queen cell virus from honeybees
      by reverse transcriptase pcr.
AB  - A reverse transcriptase PCR (RT-PCR) assay was developed for the detection of
      acute bee paralysis virus (ABPV) and black queen cell virus (BQCV), two honeybee
      viruses. Complete genome sequences were used to design unique PCR primers within
      a 1-kb region from the 3' end of both genomes to amplify a fragment of 900 bp
      from ABPV and 700 bp from BQCV. The combined guanidinium thiocyanate and silica
      membrane method was used to extract total RNA from samples of healthy and
      laboratory-infected bee pupae. In a blind test, RT-PCR successfully identified
      the samples containing ABPV and BQCV. Sensitivities were approximately 1,600
      genome equivalents of purified ABPV and 130 genome equivalents of BQCV.

PMID- 11319130
TI  - Study of the infectivity of saline-stored Campylobacter jejuni for day-old
      chicks.
AB  - The culturability of three Campylobacter jejuni strains and their infectivity for
      day-old chicks were assessed following storage of the strains in saline. The
      potential for colonization of chicks was weakened during the storage period and
      terminated 3 to 4 weeks before the strains became nonculturable. The results from
      this study suggest that the role of starved and aged but still culturable
      campylobacters may be diminutive, but even more, that the role of viable but
      nonculturable stages in campylobacter epidemiology may be negligible. Even high
      levels of maternally derived anti-campylobacter outer membrane protein serum
      antibodies in day-old chicks did not protect the chicks from campylobacter
      colonization.

PMID- 11319131
TI  - Cyclic changes in the matrix metalloproteinase system in the ovary and uterus.
AB  - With each estrous or menstrual cycle, extensive alterations occur in the
      extracellular matrix and connective tissue of the ovary and uterus. In the ovary,
      these changes occur during follicular development, breakdown of the follicular
      wall and extrusion of the oocyte, as well as during the formation and regression
      of the corpus luteum. In the uterus, the endometrium undergoes dramatic
      connective tissue turnover associated with tissue breakdown and subsequent
      regrowth during each menstrual cycle. These changes in the ovarian and uterine
      extracellular architecture are regulated, in part, by the matrix
      metalloproteinase (MMP) system. This system is comprised of both a proteolytic
      component, the MMPs, and associated inhibitors, and it is involved in connective
      tissue remodeling processes throughout the body. The current review highlights
      the key features of the MMP system and focuses on the changes in the MMPs and the
      tissue inhibitors of metalloproteinases during the dynamic remodeling that takes
      place in the ovary and uterus during the estrous and menstrual cycles.

PMID- 11319132
TI  - Changes in DNA loop domain structure during spermatogenesis and embryogenesis in
      the Syrian golden hamster.
AB  - The DNA in eukaryotic cells is organized into loop domains that are 25 to 100
      kilobases long and attached at their bases to the nuclear matrix. This
      organization plays major roles in DNA replication and transcription. We examined
      changes in DNA loop structure of the 5S rDNA gene cluster in the Syrian golden
      hamster as a function of cellular differentiation by direct visualization with
      fluorescent in situ hybridization. The 5S rDNA cluster is large enough to
      encompass more than one loop domain but small enough that individual loop domains
      can still be resolved. We found that the sizes of the 5S rDNA loops are much
      smaller, and that the numbers of loops per locus are larger, in all pluripotent
      cell types than they are in adult somatic tissue. Within the pluripotent
      spermatogenic cell lineage, the loop domain organization was cell specific. The
      loop size decreased during the early stages of spermatogenesis but did not change
      during spermiogenesis, suggesting that DNA loop structure is independent of the
      chromatin condensation that occurs when protamines replace histones. In early
      embryonic cells, the loop structure remained small, but in differentiated somatic
      cells, it became much larger. We suggest that these changes in the 5S rDNA loop
      domain structure may be related to the maintenance or loss of developmental
      potential.

PMID- 11319133
TI  - Retinoid receptors involved in the effects of retinoic acid on rat testis
      development.
AB  - We have previously shown that retinoic acid (RA) is able to act on the
      development of Leydig, Sertoli, and germ cells in the testis in culture (Livera
      et al., Biol Reprod 2000; 62:1303-1314). To identify which receptors mediate
      these effects, we have now added selective agonists and antagonists of retinoic
      acid receptors (RARs) or retinoid X receptors (RXRs) in the same organotypic
      culture system. The RAR alpha agonist mimicked most of the effects of RA on the
      cultured fetal or neonatal testis, whereas the RAR beta, gamma, and pan RXR
      agonists did not. The RAR alpha agonist decreased the testosterone production,
      the number of gonocytes, and the cAMP response to FSH of fetal testis explanted
      at 14.5 days postconception (dpc). The RAR alpha agonist disorganized the cords
      of the 14.5-dpc cultured testis and increased the cord diameter in cultured 3
      days-postpartum (dpp) testis in the same way as RA. All these RA effects could be
      reversed by an RAR alpha antagonist and were unchanged by an RAR beta/gamma
      antagonist. The RAR beta agonist, however, increased Sertoli cell proliferation
      in the 3-dpp testis in the same way as RA, and this effect was blocked by an RAR
      beta antagonist. The RAR gamma and the pan RXR agonists had no selective effect.
      These results suggest that all the effects of RA on development of the fetal and
      neonatal testis are mediated via RAR alpha, except for its effect on Sertoli cell
      proliferation, which involves RAR beta.

PMID- 11319134
TI  - Cloning and functional expression of an E box-binding protein from rat granulosa
      cells.
AB  - Ovarian granulosa cells undergo cell growth and cytodifferentiation during
      follicular maturation. In a number of tissues, the gene expression that is
      responsible for the cytodifferentiation is largely dependent on E box(es) located
      upstream of the responsible genes. In this study, we report on the cloning of
      cDNA(s) encoding E box (5'-CACGTG-3')-binding protein from a rat granulosa cell
      cDNA library using a yeast one-hybrid system. When multiple E box sequences were
      used as target, we obtained a positive clone that encodes the rat homologue of
      upstream stimulatory factor 2 (USF2). An analysis of the nucleotide sequence and
      its deduced amino acid sequence reveals that rat USF2 protein consists of 346
      amino acid residues and belongs to the basic helix-loop-helix/leucine zipper
      protein family. Northern blot analysis shows that rat USF2 mRNA exists as
      multiple forms between 1.6 and 2.2 kilobases. The size of the cloned insert was
      identical to that of the transcript of maximal length. Electrophoretic mobility
      shift assays showed that in vitro-translated rat USF2 specifically binds to the E
      box. In addition, cotransfection experiments with luciferase-reporter constructs
      in HepG2 cells reveal that the overexpression of rat USF2 leads to an increase of
      luciferase activity in the E box sequence-dependent manner. Thus, we report
      molecular cloning, expression, and functional characterization of full-length rat
      USF2 cDNA.

PMID- 11319135
TI  - Kinesin light-chain KLC3 expression in testis is restricted to spermatids.
AB  - Kinesins are tetrameric motor molecules, consisting of two kinesin heavy chains
      (KHCs) and two kinesin light chains (KLCs) that are involved in transport of
      cargo along microtubules. The function of the light chain may be in cargo binding
      and regulation of kinesin activity. In the mouse, two KLC genes, KLC1 and KLC2,
      had been identified. KLC1 plays a role in neuronal transport, and KLC2 appears to
      be more widely expressed. We report the cloning from a testicular cDNA expression
      library of a mammalian light chain, KLC3. The KLC3 gene is located in close
      proximity to the ERCC2 gene. KLC3 can be classified as a genuine light chain: it
      interacts in vitro with the KHC, the interaction is mediated by a conserved
      heptad repeat sequence, and it associates in vitro with microtubules. In mouse
      and rat testis, KLC3 protein expression is restricted to round and elongating
      spermatids, and KLC3 is present in sperm tails. In contrast, KLC1 and KLC2 can
      only be detected before meiosis in testis. Interestingly, the expression profiles
      of the three known KHCs and KLC3 differ significantly: Kif5a and Kif5b are not
      expressed after meiosis, and Kif5c is expressed at an extremely low level in
      spermatids but is not detectable in sperm tails. Our characterization of the KLC3
      gene suggests that it carries out a unique and specialized role in spermatids.

PMID- 11319136
TI  - Matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-3 are key
      regulators of extracellular matrix degradation by mouse embryos.
AB  - Embryo implantation in humans and rodents is a highly invasive yet tightly
      controlled process involving extracellular matrix (ECM) degradation. Matrix
      metalloproteinase 9 (MMP-9) has been implicated as the major facilitator of this
      ECM degradation. MMP-9 is expressed by the embryo's trophoblast cells, whereas
      tissue inhibitor of metalloproteinases 3 (TIMP-3) is expressed by the maternal
      uterine cells immediately adjacent to the trophoblast. We examined the functional
      roles of MMP-9 and TIMP-3 during in vitro ECM degradation by mouse embryos.
      Blastocysts were treated with either MMP-9 antisense or sense oligonucleotides
      and incubated on an ECM gel. The extent of ECM degradation exhibited by the
      blastocysts due to proteinase secretion was quantified. Embryos exposed to MMP-9
      antisense oligonucleotides exhibited reduced ECM-degrading activity as compared
      with controls, and this reduced activity was correlated with the level of MMP-9
      secreted by the embryos. The functional role of TIMP-3 was then examined by
      incubating blastocysts on an ECM gel that had been impregnated with various
      amounts of TIMP-3. In a dose-dependent manner, increases in TIMP-3 resulted in a
      reduction in ECM degradation and were correlated with diminished MMP-9 activity.
      These results provide important functional evidence that in vitro ECM degradation
      is regulated by embryo-derived MMP-9 and ECM-derived TIMP-3.

PMID- 11319138
TI  - Protein tyrosine phosphorylation in sperm during gamete interaction in the mouse:
      the influence of glucose.
AB  - A key intracellular event during capacitation is protein tyrosine
      phosphorylation, but its involvement during sperm interaction with the oocyte has
      not been investigated. Glucose is necessary to achieve fertilization and thus may
      have an influence on sperm protein tyrosine phosphorylation. The objectives of
      this study were to 1) visualize protein tyrosine phosphorylation patterns in
      sperm during capacitation and interaction with the oocyte and 2) determine the
      influence of glucose. Protein tyrosine phosphorylation was investigated by
      Western analysis and immunofluorescence. Protein tyrosine phosphorylation was
      increased during capacitation, and immunofluorescence revealed that zona binding
      and gamete fusion were correlated with an increase in tyrosine phosphorylation of
      proteins in the midpiece. During capacitation, the absence of glucose led to a
      delay in the appearance of protein tyrosine phosphorylation. Following binding to
      the zona pellucida and the oolemma, tyrosine phosphorylation in the flagellum was
      also delayed in the absence of glucose and resulted in a significant inhibition
      of the midpiece phosphorylation. The correlation between successful gamete fusion
      and the tyrosine phosphorylation of midpiece proteins suggests that the effect of
      glucose on sperm-oocyte interaction is mediated through regulation of protein
      tyrosine phosphorylation in a specific area of the fertilizing sperm.

PMID- 11319137
TI  - Sperm factor induces intracellular free calcium oscillations by stimulating the
      phosphoinositide pathway.
AB  - Injection of a porcine cytosolic sperm factor (SF) or of a porcine testicular
      extract into mammalian eggs triggers oscillations of intracellular free calcium
      ([Ca(2+)](i)) similar to those initiated by fertilization. To elucidate whether
      SF activates the phosphoinositide (PI) pathway, mouse eggs or SF were incubated
      with U73122, an inhibitor of events leading to phospholipase C (PLC) activation
      and/or of PLC itself. In both cases, U73122 blocked the ability of SF to induce
      [Ca(2+)](i) oscillations, although it did not inhibit Ca(2+) release caused by
      injection of inositol 1,4,5-triphosphate (IP(3)). The inactive analogue, U73343,
      had no effect on SF-induced Ca(2+) responses. To determine at the single cell
      level whether SF triggers IP(3) production concomitantly with a [Ca(2+)](i) rise,
      SF was injected into Xenopus oocytes and IP(3) concentration was determined using
      a biological detector cell combined with capillary electrophoresis. Injection of
      SF induced a significant increase in [Ca(2+)](i) and IP(3) production in these
      oocytes. Using ammonium sulfate precipitation, chromatographic fractionation, and
      Western blotting, we determined whether PLCgamma1, PLCgamma2, or PLCdelta4 and/or
      its splice variants, which are present in sperm and testis, are responsible for
      the Ca(2+) activity in the extracts. Our results revealed that active fractions
      do not contain PLCgamma1, PLCgamma2, or PLCdelta4 and/or its splice variants,
      which were present in inactive fractions. We also tested whether IP(3) could be
      the sensitizing stimulus of the Ca(2+)-induced Ca(2+) release mechanism, which is
      an important feature of fertilized and SF-injected eggs. Eggs injected with
      adenophostin A, an IP(3) receptor agonist, showed enhanced Ca(2+) responses to
      CaCl(2) injections. Thus, SF, and probably sperm, induces [Ca(2+)](i) rises by
      persistently stimulating IP(3) production, which in turn results in long-lasting
      sensitization of Ca(2+)-induced Ca(2+) release. Whether SF is itself a PLC or
      whether it acts upstream of the egg's PLCs remains to be elucidated.

PMID- 11319139
TI  - Steroid hormones stimulate gonadotrophs in juvenile male African catfish (Clarias
      gariepinus).
AB  - In juvenile African catfish (Clarias gariepinus), the pituitary LH content
      strongly increased after the beginning of spermatogonial proliferation. We
      hypothesized that a signal of testicular origin is involved in stimulating the
      gonadotrophs. We investigated the effects of castration and sex steroid treatment
      on gonadotrophs in juvenile males by quantifying LH production and release and LH
      subunit transcript levels and by examining gonadotroph morphology and
      proliferation. Castration reduced but did not abolish the maturation-associated
      elevation in pituitary LH content. Treatment with testosterone but not with 11
      ketotestosterone, an otherwise potent androgen in fish, reversed the castration
      induced decrease of pituitary LH levels. An increased pituitary LH content was
      accompanied by an increased number of cytologically mature gonadotrophs. However,
      no evidence was found for gonadotroph proliferation, so that quiescent
      gonadotrophs may have become activated. Although 11-ketotestosterone treatments
      had no effect in castrated males, this androgen attenuated gonadotroph activation
      in intact males. Because androgen production in juvenile catfish is downregulated
      by treatment with 11-ketotestosterone, its inhibitory effects on gonadotrophs in
      gonad-intact males may be due to suppression of Leydig cell testosterone
      production, which appears to be a limiting factor for the activation of catfish
      gonadotrophs. Aromatizable androgens may have opposite effects on fish
      (stimulatory) and mammalian (inhibitory) gonadotrophs.

PMID- 11319140
TI  - Differential effect of hexoses on hamster embryo development in culture.
AB  - The effects of glucose, fructose, and galactose on hamster embryo development in
      the absence of phosphate were studied in culture. One- and two-cell embryos were
      cultured to the blastocyst stage in HECM-9 medium without hexose or in medium
      with increasing concentrations of hexoses. Embryo development, cell number, and
      cell allocation were assessed in blastocysts. Blastocyst viability was determined
      by transfer to pseudopregnant recipients. Although 0.25 mM fructose increased
      mean cell number, low glucose concentrations had no stimulatory effect on
      development to blastocyst. Both galactose and 5.0 mM glucose were detrimental to
      embryos. Addition of 0.5 mM glucose increased implantation and fetal viability as
      compared with controls. Compared with 0.5 mM glucose, treatment with 0.25 mM
      fructose gave similar implantation and fetal viability, whereas 5.0 mM glucose
      tended to decrease implantation and significantly decreased fetal development.
      These data demonstrate that morphology is a poor indicator of embryo viability
      and that exposure of preimplantation embryos to glucose or fructose is important
      for embryo viability post-transfer. Although no difference in blastocyst
      viability was detected between embryos cultured with 0.25 mM fructose and those
      cultured with 0.5 mM glucose, increased cell numbers obtained with fructose
      suggest that fructose may be more appropriate than glucose for inclusion in
      culture medium.

PMID- 11319141
TI  - Ultrastructural morphometry of bovine blastocysts produced in vivo or in vitro.
AB  - The objective of this study was to compare the ultrastructure of bovine
      blastocysts produced in vivo or in vitro by using morphometric analysis.
      Blastocysts produced in vivo (multiple ovulations, MO) were obtained from
      superovulated Holstein cows. For blastocysts produced in vitro, cumulus-oocyte
      complexes aspirated from ovaries of Holstein cows were matured and fertilized in
      vitro. At 20 h postinsemination (hpi), zygotes were distributed into one of three
      culture media: 1) IVPS (in vitro produced with serum): TCM-199 + 10% estrous cow
      serum (ECS); 2) IVPSR (in vitro produced with serum restriction): TCM-199 + 1%
      BSA until 72 hpi, followed by TCM-199 + 10% ECS from 72 to 168 hpi; and 3) mSOF
      (modified synthetic oviductal fluid): mSOF + 0.6% BSA. At 168 hpi, six or seven
      grade 1 blastocysts from each of the four treatments (MO, IVPS, IVPSR, and mSOF)
      were fixed and prepared for transmission electron microscopy. Random micrographs
      of each blastocyst were used to determine the volume density of cellular
      components. Overall, as blastocysts progressed in development, the volume
      densities of cytoplasm and intercellular space decreased (P < 0.05) and the
      volume densities of mature mitochondria, nuclei, blastocoele, and apoptotic
      bodies increased (P < 0.05). Across treatments, the proportional volumes of
      nuclei and inclusion bodies were increased in inner cell mass cells compared with
      trophectoderm cells for mid- and expanded blastocysts. For blastocysts produced
      in vitro, the volume density of mitochondria was decreased (P < 0.05) as compared
      with that of blastocycts produced in vivo. The proportional volume of vacuoles
      was increased (P < 0.05) in blastocysts from the mSOF treatment as compared with
      blastocysts produced in vivo. For mid- and expanded blastocysts from all three in
      vitro treatments, the volume density of lipid increased (P < 0.05) and the volume
      density of nuclei decreased (P < 0.05) compared with those of blastocysts
      produced in vivo. In conclusion, blastocysts produced in vitro possessed
      deviations in volume densities of organelles associated with cellular metabolism
      as well as deviations associated with altered embryonic differentiation. However,
      the specific nature of these deviations varied with the type of culture
      conditions used for in vitro embryo production.

PMID- 11319143
TI  - Effects of the estrous cycle, pregnancy, and interferon tau on 2',5'
      oligoadenylate synthetase expression in the ovine uterus.
AB  - The enzymes which comprise the 2',5'-oligoadenylate synthetase (OAS) family are
      interferon (IFN) stimulated genes which regulate ribonuclease L antiviral
      responses and may play additional roles in control of cellular growth and
      differentiation. This study characterized OAS expression in the endometrium of
      cyclic and pregnant ewes as well as determined effects of IFNtau and progesterone
      on OAS expression in cyclic or ovariectomized ewes and in endometrial epithelial
      and stromal cell lines. In cyclic ewes, low levels of OAS protein were detected
      in the endometrial stroma (S) and glandular epithelium (GE). In early pregnant
      ewes, OAS expression increased in the S and GE on Day 15. OAS expression in the
      lumenal epithelium (LE) was not detected in uteri from either cyclic or pregnant
      ewes. Intrauterine administration of IFNtau stimulated OAS expression in the S
      and GE, and this effect of IFNtau was dependent on progesterone. Ovine
      endometrial LE, GE, and S cell lines responded to IFNtau with induction of OAS
      proteins. In all three cell lines, the 40/46-kDa OAS forms were induced by
      IFNtau, whereas the 100-kDa OAS form appeared to be constitutively expressed and
      not affected by IFNtau. The 69/71-kDa OAS forms were induced by IFNtau in the S
      and GE cell lines, but not in the LE. Collectively, these results indicate that
      OAS expression in the endometrial S and GE of the early pregnant ovine uterus is
      directly regulated by IFNtau from conceptus and requires the presence of
      progesterone.

PMID- 11319142
TI  - DNA damaging agents increase gadd153 (CHOP-10) messenger RNA levels in bovine
      preimplantation embryos cultured in vitro.
AB  - DNA damage and other forms of stress are believed to be important factors in
      reducing the efficiency of in vitro embryo transfer techniques in farm animals.
      The expression of mRNAs from stress-responsive genes such as gadd153 (CHOP-10,
      ddit3) may provide a means of assessing the quality of embryos produced in vitro.
      Treatment of bovine granulosa cell cultures with the DNA-damaging agents, methyl
      methane-sulphonate (MMS) or sodium arsenite, induced the expression of an mRNA,
      which hybridized with the hamster gadd153 cDNA. Part of the corresponding bovine
      cDNA was amplified by nested polymerase chain reaction (PCR), cloned, and
      sequenced. Using a sensitive reverse transcriptase-PCR assay we have investigated
      the expression of gadd153 and beta-actin in blastocyst-stage bovine embryos
      treated with MMS or sodium arsenite. Both agents produced an increase in the
      ratio of gadd153 mRNA relative to beta-actin. These results show that there are
      changes in gene expression in blastocyst-stage bovine embryos in response to
      genotoxic stress, suggesting that an increase in gadd153 mRNA is a useful marker
      of DNA damage and metabolic stress in preimplantation embryos.

PMID- 11319144
TI  - Meiotic expression of the cyclin H/Cdk7 complex in male germ cells of the mouse.
AB  - Cell division requires that cyclin-dependent kinases (Cdks) be activated by
      phosphorylation. In mitotic cells, this is accomplished by the Cdk-activating
      kinase (CAK), which is a complex of cyclin H and Cdk7. There are currently no
      data on the role of CAK in meiotic cells. Previously, we have shown that cyclin
      A1 is meiosis-specific and forms an active kinase with Cdk2. Because cyclin A1 is
      required for meiosis, and its associated kinase must be phosphorylated
      (activated), we propose that cyclin H/Cdk7 function to activate cyclin A1/Cdk2 in
      meiotic cells. Here, we show that cyclin H and Cdk7 are present during meiosis.
      Using reverse transcription-polymerase chain reaction and in situ hybridization,
      we show that the mRNAs encoding cyclin H and Cdk7 are abundant in spermatocytes.
      Immunohistochemistry localized cyclin H and Cdk7 to the nucleus of spermatocytes
      in stages IV to XII of the spermatogenic cycle, overlapping the same stages that
      express cyclin A1-associated kinases. Finally, immunoprecipitation and histone H1
      kinase assays of cyclin H and Cdk7 from testicular extracts show that these
      proteins interact to form an active kinase. We conclude that cyclin H/Cdk7
      complexes are present and during meiosis, form active complexes in testicular
      cells and are strong candidates for the activating kinase for cyclin A1
      associated kinase.

PMID- 11319146
TI  - Effect of age and breeding season on the developmental capacity of oocytes from
      unstimulated and follicle-stimulating hormone-stimulated rhesus monkeys.
AB  - Effects of age and season on the developmental capacity of oocytes from
      unstimulated and FSH-stimulated rhesus monkeys were examined. Immature cumulus
      oocyte complexes were matured in vitro in modified CMRL-1066 medium containing
      20% bovine calf serum and subjected to in vitro fertilization followed by embryo
      culture. After fertilization, ova from unstimulated prepubertal monkeys displayed
      lower development to morula (4%) than those from unstimulated adult females (18%
      in breeding season and 22% in nonbreeding season). No developmental difference
      was found between ova from unstimulated adult monkeys in breeding and nonbreeding
      seasons. However, ova from FSH-primed prepubertal monkeys displayed greater
      development to blastocyst stage (54%) than those from adult monkeys in the
      breeding season (16%) and nonbreeding season (0%); and ova from FSH-primed adult
      females in the breeding season had significantly (P < 0.05) greater developmental
      competence than those obtained in the nonbreeding season (> or = morula stage,
      54% vs. 3%; blastocyst stage, 16% vs. 0%). These data indicate that 1) rhesus
      monkey oocytes acquire developmental competence in a donor age-dependent manner,
      and 2) animal age and breeding season modulate the effect of FSH on oocyte
      developmental competence in the rhesus monkey.

PMID- 11319145
TI  - Primate spermatogonial stem cells colonize mouse testes.
AB  - In mice, transplantation of spermatogonial stem cells from a fertile male to the
      seminiferous tubules of an infertile recipient male results in progeny with donor
      derived haplotype. Attempts to extend this approach by transplanting human testis
      cells to mice have led to conflicting claims that no donor germ cells persisted
      or that human spermatozoa were produced in the recipient. To examine this issue
      we used the baboon, a primate in which testis cell populations of several ages
      could be obtained for transplantation, and demonstrate that donor spermatogonial
      stem cells readily establish germ cell colonies in recipient mice, which exist
      for periods of at least 6 mo. However, differentiation of germ cells toward the
      lumen of the tubule and production of spermatozoa did not occur. The presence of
      baboon spermatogonial stem cells and undifferentiated spermatogonia in mouse
      seminiferous tubules for long periods after transplantation indicates that
      antigens, growth factors, and signaling molecules that are necessary for
      interaction of these cells and the testis environment have been preserved for 100
      million years of evolutionary separation. Because germ cell differentiation and
      spermatogenesis did not occur, the molecules necessary for this process appear to
      have undergone greater divergence between baboon and mouse.

PMID- 11319147
TI  - Status of p53, p21, mdm2, pRb proteins, and DNA methylation in gonocytes of
      control and gamma-irradiated rats during testicular development.
AB  - In fetal and newborn rat testes, gonocytes, which stop cycling for about 8 days,
      become highly radiosensitive. The presence of p53, p21, mdm2, and pRb, which are
      involved in cell cycle, apoptosis control, or both, were studied by
      immunohistochemistry to determine if their expression is related to this
      radiosensitivity. A strong cytoplasmic expression of p53 and p21 was detected.
      Cytoplasmic expression of p53 occurred only in arrested gonocytes, whereas that
      of p21 was observed before and after the block. P21 was found to colocalize with
      mitochondria. No expression of mdm2 was detected and pRb was present only when
      the gonocytes started cycling again. In animals exposed to 1.5 Gy of gamma
      irradiation at Day 19 postcoitum, p53 expression was prolonged in time, whereas
      no change was observed in p21 amounts and localization, compared with controls.
      Using antibodies against 5-methyl cytosine, it was shown that gonocyte DNA passed
      from a hypomethylated to a methylated status 1 day after gonocytes stopped
      cycling. A prolonged survival of gonocytes after exposure to radiation was
      followed by their progressive apoptosis, which finally involved the entire
      gonocyte population between Days 6 and 12 postpartum. The elevated but delayed
      sensitivity of gonocytes to genotoxic stress may be related to the unusual
      expression of p53 and p21, which may itself be related to the large DNA
      methylation changes.

PMID- 11319149
TI  - Aromatase messenger RNA is derived from the proximal promoter of the aromatase
      gene in Leydig, Sertoli, and germ cells of the rat testis.
AB  - It has long been recognized that individual cell types within the testes possess
      the capacity to synthesize estrogen. A number of studies on different species
      have demonstrated that the levels of aromatase expression and the patterns of
      regulation are distinct between the different cell types of the testes. Whereas a
      variety of promoters have been shown to contribute to the patterns of aromatase
      expression in different cell lineages, studies using ovarian RNA, testis RNA, and
      Leydig cell tumor lines have demonstrated that the same promoter (promoter II)
      was used in each. Recent experiments using potent aromatase inhibitors or
      analysis of animals in which the genes encoding the estrogen receptor-alpha (ER
      alpha) or the aromatase, P450, are defective, have confirmed the importance of
      local estrogen formation in normal testicular function. In order to permit
      experiments to identify the elements controlling aromatase expression in the
      individual cell compartments of the testes, we prepared RNA from purified
      preparations of Leydig, Sertoli, and germ cells. Using specific oligonucleotide
      primers, the sites of initiation of the aromatase mRNA were determined using
      rapid amplification of cDNA ends (RACE) and nucleotide sequence analysis of the
      resulting cDNA fragments. Our results indicate that aromatase mRNA is derived
      from the proximal promoter (PII) of the aromatase gene in each of the major cell
      types of the rat testes.

PMID- 11319148
TI  - Expression and molecular characterization of estrogen receptor alpha messenger
      RNA in male reproductive organs of adult goats.
AB  - The fact that male estrogen receptor alpha (ERalpha) knockout mice are infertile
      indicates a role for this receptor in male reproduction. Here, objectives were to
      evaluate ERalpha expression in male goat reproductive tissues at the
      transcriptional level using RNase protection assay (RPA) and in situ
      hybridization (ISH), and to clone a partial cDNA for caprine ERalpha using
      reverse transcription-polymerase chain reaction (RT-PCR). For RPA and ISH
      procedures, a radiolabeled antisense cRNA probe, generated in vitro from the
      ovine oER8 cDNA template, was employed. Evaluations were made on individual
      samples obtained from adult goats. Labeled cRNA sense probe was used as a
      negative control in ISH. A 530-base pair amplicon was generated by RT-PCR from
      efferent ductules (EDs), epididymis (EP), and testis, cloned from the ED and EP,
      and sequenced. The caprine ERalpha (cERalpha) cDNA displayed 81%-96% sequence
      identity with that of other species. A signal indicative of ERalpha mRNA was
      identified by both RT-PCR and RPA in all tissues, but was strongest in the ED.
      Compared with ED, ERalpha signal was sixfold lower in the EP, and 66-fold lower
      in the testis. Similarly, strong ERalpha expression was observed in ED
      epithelium, whereas little or no signal was detected in EP or testis by ISH.
      Thus, among different segments of the male reproductive tract and testis, the
      highest level of ERalpha mRNA expression was found in epithelium of the ED.

PMID- 11319150
TI  - Phosphorylation of mitogen-activated protein kinase is regulated by protein
      kinase C, cyclic 3',5'-adenosine monophosphate, and protein phosphatase
      modulators during meiosis resumption in rat oocytes.
AB  - Mitogen-activated protein (MAP) kinase, protein kinase C (PKC), cAMP, and okadaic
      acid (OA)-sensitive protein phosphatases (PPs) have been suggested to be involved
      in oocyte meiotic resumption. However, whether these protein kinases and
      phosphatases act by independent pathways or interact with each other in
      regulating meiosis resumption is unknown. In the present study, we aimed to
      determine the regulation of meiosis resumption and MAP kinase phosphorylation by
      PKC, cAMP, and OA-sensitive PPs in rat oocytes using an in vitro oocyte
      maturation system and Western blot analysis. We found that ERK1 and ERK2 isoforms
      of MAP kinases existed in a dephosphorylated (inactive) form in germinal vesicle
      breakdown (GVBD)-incompetent and GVBD-competent germinal vesicle intact (GVI)
      oocytes as well as GVBD oocytes at equivalent levels. These results indicate that
      MAP kinases are not responsible for the initiation of normal meiotic resumption
      in rat oocytes. However, when GVBD-incompetent and GVBD-competent oocytes were
      incubated in vitro for 5 h, MAP kinases were phosphorylated (activated) in GVBD
      competent oocytes, but not in meiotic-incompetent oocytes, suggesting that
      oocytes acquire the ability to phosphorylate MAP kinase during acquisition of
      meiotic competence. We also found that both meiosis resumption and MAP kinase
      phosphorylation were inhibited by PKC activation or cAMP elevation. Moreover,
      these inhibitory effects were overcome by OA, which inhibited PP1/PP2A
      activities. These results suggest that both cAMP elevation and PKC activation
      inhibit meiosis resumption and MAP kinase phosphorylation at a step prior to OA
      sensitive protein phosphatases. In addition, inhibitory effects of cAMP elevation
      on meiotic resumption and MAP kinase phosphorylation were not reversed by
      calphostin C-induced PKC inactivation, indicating that cAMP inhibits both meiotic
      resumption and MAP kinase activation in a PKC-independent manner.

PMID- 11319151
TI  - Outer dense fiber proteins are dominant postobstruction autoantigens in adult
      Lewis rats.
AB  - Obstruction of the male reproductive tract commonly results in generation of
      antisperm autoantibodies. However, only a few of the sperm autoantigens
      recognized by these antibodies have been characterized. To identify
      postobstruction rat sperm autoantigens, sperm proteins were separated by two
      dimensional(2-D) gel electrophoresis. Spots corresponding to proteins that were
      stained by at least 50% of postvasectomy rat sera on 2-D Western blots were
      removed from polyacrylamide gels and microsequenced by tandem mass spectrometry.
      From a total of 21 spots, 12 contained peptides that matched solely to either of
      two outer dense fiber proteins, odf1 or odf2. Six additional spots contained
      peptides comprising odf1 or odf2 and were accompanied by peptides representing
      other proteins. Only three spots lacked outer dense fiber peptides but did
      contain sequences of other known proteins. The results indicate that the outer
      dense fiber proteins odf1 and odf2 are dominant postobstruction autoantigens
      because they were detected in the majority of the immunoreactive protein spots
      examined. Possible explanations for this observation include the abundance of
      outer dense fiber proteins in spermatozoa, slow solubility, which may provide a
      sustained supply of antigen, and testis-specific expression during
      spermiogenesis.

PMID- 11319152
TI  - Effects of acute stanozolol treatment on puberty in female rats.
AB  - The effects of anabolic-androgenic steroid (AAS) abuse on the onset of puberty in
      female adolescents are largely unknown. This study assessed the acute effects of
      one AAS, stanozolol, on pubertal onset in the female rat. A single injection of
      stanozolol (5 mg/kg) on Postnatal Day (PN) 21 advanced vaginal opening but did
      not alter the onset of vaginal estrus. Higher doses of stanozolol treatment (10
      and 25 mg/kg) also advanced vaginal opening but had no effect on vaginal estrus.
      The advancement of vaginal opening by stanozolol (5 mg/kg) was prevented by the
      concomitant administration of the pure antiestrogen ICI 182,780 (1 mg/kg) on PN20
      22. Administration of the androgen receptor antagonist flutamide (10 mg/kg twice
      daily) on PN20-22 had no effect on the advancement of vaginal opening by
      stanozolol. Stanozolol treatment also advanced vaginal opening in ovariectomized
      rats. Perivaginal injections of a low dose of stanozolol (0.05 mg) on PN21 and
      PN23 also advanced vaginal opening. These results suggest that stanozolol is
      acting directly at estrogen receptors in the vaginal epithelium to advance
      vaginal opening and that prepubertal stanozolol treatment does not induce true
      precocious puberty.

PMID- 11319153
TI  - Melanin-concentrating hormone stimulates the release of luteinizing hormone
      releasing hormone and gonadotropins in the female rat acting at both median
      eminence and pituitary levels.
AB  - The purpose of this study was to investigate whether melanin-concentrating
      hormone (MCH) acts directly on the median eminence and on the anterior pituitary
      of female rats regulating LHRH and gonadotropin release. In addition,
      immunohistochemistry was used to examine the density and distribution of MCH
      immunoreactive fibers in the median eminence of proestrous rats. MCH
      immunoreactive fibers were found in both the internal and external layers of the
      median eminence and in close association with hypophysial portal vessels. In the
      first series of in vitro experiments, median eminences and anterior pituitaries
      were incubated in Krebs-Ringer bicarbonate buffer containing two MCH
      concentrations (10(-10) and 10(-8) M). The lowest MCH concentration (10(-10) M)
      increased (P < 0.01) LHRH release only from proestrous median eminences. Anterior
      pituitaries incubated with both MCH concentrations also showed that 10(-10) M MCH
      increased gonadotropin release only from proestrous pituitaries. In the second
      series of experiments, median eminences and pituitaries from proestrous rats were
      incubated with graded concentrations of MCH. MCH (10(-10) and 10(-9) M) increased
      (P < 0.01) LHRH release from the median eminence, and only 10(-10) M MCH
      increased (P < 0.01) LH and FSH release from the anterior pituitary. The effect
      of MCH on the stimulation of both gonadotropins from proestrous pituitaries was
      similar to the effect produced by LHRH. Simultaneous incubation of pituitaries
      with MCH and LHRH did not modify LH but increased the FSH release induced by
      LHRH. The present results suggest that MCH could be involved in the regulation of
      preovulatory gonadotropin secretion.

PMID- 11319154
TI  - Gonad-specific expression of two novel chicken complementary DNA isoforms.
AB  - Differential display reverse transcription polymerase chain reaction was used to
      isolate a novel cDNA clone (C47) that was initially shown to be downregulated in
      senescent chicken embryo fibroblast cells. In a tissue environment, C47
      transcripts were only detected in gonadal tissue. The expression of the larger
      isoform (C47L) was essentially restricted to the ovary, and the smaller isoform
      (C47S) was predominately expressed in the testis. Although levels of the C47L
      mRNA were relatively high in both the small white and the developing larger
      follicles, there was very low expression in regressed and postovulated follicles.
      Nucleotide sequence analysis indicated that two different transcripts of the
      single-copy C47 gene were generated by differential polyadenylation in the 3'
      untranslated region. As a result of a single nucleotide deletion, the C47L mRNA
      produced a smaller 48-kDa protein, and the C47S mRNA generated a larger 57-kDa
      protein when both were translated in vitro. Both protein isoforms were shown to
      contain conserved C2H2 Zn finger motifs and nuclear localization signals
      suggestive of being putative transcription factors. These results suggest that
      the C47L and C47S isoforms might play an important role in the regulation and
      maintenance of ovarian and testicular functions, respectively, in the chicken.

PMID- 11319155
TI  - Mediators of interferon gamma-initiated signaling in bovine luteal cells.
AB  - Interferon gamma (IFNgamma) has been implicated as a mediator of luteal
      steroidogenesis and cell fate. IFNgamma-initiated signaling events, although
      implied by studies in cell lines, have yet to be described in primary luteal
      cells. The objective of these studies was to begin to characterize IFNgamma
      initiated signaling within luteal cells. Dispersed bovine luteal cell cultures
      were challenged with increasing levels of bovine recombinant IFNgamma (0-1000 U)
      or IFNgamma (200 U) in the presence or absence of tumor necrosis factor alpha
      (TNFalpha, 10 ng/ml) over time (short term, 0-60 min; long term, 0, 24, 48 h).
      Fractionated or total cell lysates were evaluated by the Western blotting
      technique to determine the changes in the levels of signal transducers and
      activators of transcription (STAT), interferon regulatory factor 1 (IRF-1), and I
      kappa B alpha (IkappaB-alpha). Utilizing antibodies that recognize the
      nonphosphorylated forms of STAT-1 and STAT-3, it was determined that levels of
      STAT-1 and STAT-3 in total cell lysates were constitutively expressed and did not
      change in response to treatment with IFNgamma or TNFalpha. In contrast, nuclear
      levels of STAT-1 and phosphorylated STAT-3 were elevated in a time-dependent
      manner in response to IFNgamma treatment. Furthermore, IFNgamma and TNFalpha
      treatment elevated levels of IRF-1 within 2 h. TNFalpha-induced increases in the
      levels of IRF-1 were transient, whereas the levels of IRF-1 in response to
      IFNgamma treatment remained elevated at 48 h. These data suggest that IFNgamma
      treatment can activate members of the STAT pathway, resulting in increased levels
      of IRF-1. TNFalpha treatment induced a rapid decrease in the levels of IkappaB
      alpha. IFNgamma treatment did not alter the levels of IkappaB-alpha and failed to
      inhibit the TNFalpha-initiated decrease in the levels of IkappaB-alpha. The
      present experiment demonstrates that the steroidogenic cells of the corpus luteum
      have the capacity to respond to IFNgamma via activation of STAT and IRF-1,
      providing further evidence that IFNgamma may be involved in the luteolytic
      process. These data also suggest that IFNgamma does not signal through the
      nuclear factor kappa B cell survival signaling pathway.

PMID- 11319156
TI  - Effect of fibroblast donor cell age and cell cycle on development of bovine
      nuclear transfer embryos in vitro.
AB  - The effects of cell cycle stage and the age of the cell donor animal on in vitro
      development of bovine nuclear transfer embryos were investigated. Cultures of
      primary bovine fibroblasts were established from animals of various ages, and the
      in vitro life span of these cell lines was analyzed. Fibroblasts from both
      fetuses and calves had similar in vitro life spans of approximately 30 population
      doublings (PDs) compared with 20 PDs in fibroblasts obtained from adult animals.
      When fibroblasts from both fetuses and adult animals were cultured as a
      population, the percentage of cells in G1 increased linearly with time, whereas
      the percentage of S-phase cells decreased proportionately. Furthermore, the
      percentage of cells in G1 at a given time was higher in adult fibroblasts than in
      fetal fibroblasts. To study the individual cells from a population, a shake-off
      method was developed to isolate cells in G1 stage of the cell cycle and evaluate
      the cell cycle characteristics of both fetal and adult fibroblasts from either
      25% or 100% confluent cultures. Irrespective of the age, the mean cell cycle
      length in isolated cells was shorter (9.6-15.5 h) than that observed for cells
      cultured as a population. Likewise, the length of the G1 stage in these isolated
      cells, as indicated by 5-bromo-deoxyuridine labeling, lasted only about 2-3 h.
      There were no differences in either the number of cells in blastocysts or the
      percentage of blastocysts between the embryos reconstructed with G1 cells from
      25% or 100% confluent cultures of fetal or adult cell lines. This study suggests
      that there are substantial differences in cell cycle characteristics in cells
      derived from animals of different ages or cultured at different levels of
      confluence. However, these factors had no effect on in vitro development of
      nuclear transfer embryos.

PMID- 11319157
TI  - Endothelium-derived nitric oxide synthase protein expression in ovine placental
      arteries.
AB  - During the third trimester, fetoplacental and uterine blood flows increase
      dramatically to meet the high metabolic demands of the growing fetus. We
      hypothesized that the expression of endothelial nitric oxide synthase (eNOS) in
      fetoplacental artery endothelium and the concentrations of nitric oxide (NO) and
      cyclic GMP (cGMP) in amniotic fluid (AF) are increased during the third trimester
      of ovine gestation. Placental arteries and AF were collected from ewes at 110,
      120, 130, and 142 days of gestation (n = 24; mean +/- SEM term = 145 +/- 3 days).
      Expression of eNOS protein was measured in intact and denuded placental arteries
      and in endothelium-derived protein by Western analysis and confirmed by
      immunohistochemistry. Concentrations of NO (nitrates plus nitrites) and cGMP were
      determined in AF. Placental artery eNOS protein expression was localized to the
      endothelium, where it was markedly greater than in vascular smooth muscle.
      Placental artery endothelium-derived eNOS expression and AF cGMP concentrations
      were similar at 110 and 120 days of gestation; however, both peaked at 130 days
      at levels two- to threefold above baseline (P < 0.05) before returning to
      baseline at 142 days of pregnancy. The AF NO (nitrates plus nitrites) levels,
      however, increased progressively between 120 days of gestation and term (P <
      0.05). We concluded that endothelium-derived placental artery eNOS levels, AF NO
      (nitrates plus nitrites), and AF cGMP were markedly increased during the third
      trimester, thus supporting a role for NO-mediated elevations in cGMP in the
      control of fetoplacental blood flow.

PMID- 11319158
TI  - Reversible inhibition of spermatogenesis in rats using a new male contraceptive,
      1-(2,4-dichlorobenzyl)-indazole-3-carbohydrazide.
AB  - The oral male contraceptive agent 1-(2,4-dichlorobenzyl)-indazole-3
      carbohydrazide (AF2364) is a new analogue of indazole-carboxylic acid. AF2364 was
      orally administered to rats at 50 mg/kg body weight once weekly for five
      consecutive weeks. The effects on fertility efficacy, hormonal profile, organ
      weights, tissue morphology, and serum microchemistry were examined. Complete
      infertility was noted in rats 29 days after the initial dose of AF2364 and
      continued until 90 days. Fertility resumed in 25% of the group after 104 days and
      had resumed in 75% of the rats by the last mating at 197 days. Morphological
      examination of the testis showed rapid exfoliation of elongated spermatids and
      the generation of large multinucleated cells 6 days after the first treatment,
      with depletion of most germ cells after 40 days. Normal spermatogenesis was noted
      in 95% of the tubules in the animals that were fertile at 210 days. Morphological
      analysis of the epididymal compartments revealed reduced lumen size, whereas the
      prostate exhibited an increase in the glandular lumen with a reduction in
      epithelium height. No morphological changes were detected in the kidney, liver,
      and cerebrum by light microscopy. Kidney and liver function, as evaluated by
      serum chemistry, were not affected by the drug treatment. AF2364 did not alter
      the levels of FSH, and only minimal changes were noted for LH and testosterone,
      suggesting that the hypothalamic-pituitary-testicular axis was not affected.
      These results illustrate the potential of AF2364 as a male contraceptive.

PMID- 11319159
TI  - Expression of cystic fibrosis transmembrane conductance regulator in rat efferent
      duct epithelium.
AB  - The expression of cystic fibrosis transmembrane conductance regulator (CFTR) was
      studied in rat efferent ducts. Under whole-cell patch-clamp condition, efferent
      duct cells responded to intracellular cAMP with a rise in inward current. The
      cAMP-activated current exhibited a linear I-V relationship and time- and voltage
      independent characteristics. The current was inhibited by the Cl(-) channel
      blocker diphenylamine 2,2'-dicarboxylic acid (DPC) in a voltage-dependent manner
      and reversed at 24 +/- 0.5 mV, close to the equilibrium potential for Cl(-) (30
      mV), suggesting that the current was Cl(-) selective. The cAMP-activated current
      displayed a permeability sequence of Br(-) > Cl(-) > I(-). Short-circuit current
      measurement in cultured rat efferent duct epithelia also revealed a cAMP
      activated inward current inhibitable by DPC. These electrophysiological
      properties of the cAMP-activated Cl(-) conductance in the efferent duct were
      consistent with those reported for CFTR. In support of the functional studies,
      reverse transcription polymerase chain reaction revealed the presence of CFTR
      message in cultured efferent duct epithelium. Immunohistochemical studies in
      intact rats also demonstrated CFTR protein at the apical membrane of the
      principal cells of efferent duct. CFTR may play a role in modulating fluid
      transport in the efferent duct.

PMID- 11319160
TI  - Immunolocalization of nucleolar proteins during bovine oocyte growth, meiotic
      maturation, and fertilization.
AB  - During the growth phase of the bovine oocyte transcripts, polypeptides and
      ribosomes are accumulated in the oocyte to drive and sustain future meiotic
      maturation, fertilization, and early embryonic development. The oocyte also
      furnishes the early embryo with the components required to establish a functional
      transcriptionally active nucleolus at the time of maternal embryonic transition.
      The aim of the present study was to describe the behavior of key components of
      the nucleolus. The temporal localization of nucleolar proteins fibrillarin,
      nucleophosmin, nucleolin, RNA polymerase I (RNA pol I), topoisomerase I, upstream
      binding factor (UBF), and coilin 5P10 was investigated in growing and fully grown
      immature bovine oocytes during in vitro maturation and during the first
      postfertilization cell cycle using whole-mount immunocytochemistry and confocal
      microscopy. During the oocyte growth phase, fibrillarin, nucleophosmin,
      nucleolin, RNA pol I, and UBF were localized to the oocyte nucleolus. On
      completion of the growth phase, nucleolin and nucleophosmin appeared to migrate
      to the periphery of the nucleolus and into the nucleoplasm, and the proportion of
      oocytes displaying RNA pol I localization had decreased. Topoisomerase I was not
      detected at any stage. Fibrillarin appeared to be localized to large foci within
      the nucleolus and/or nucleoplasm. Nucleophosmin and nucleolin labeling was
      characterized by a homogeneous signal over the nucleolus. RNA pol I and UBF were
      characterized by the localization of the antibodies to individual or clustered
      foci in the nucleolus and/or nucleoplasm. Following oocyte nucleus breakdown
      (ONBD), the proteins appeared to disperse into the cytoplasm. All proteins were
      undetectable during meiotic maturation and were not relocalized until 5-10 h
      postinsemination (hpi). UBF was localized to the fertilizing sperm head of most
      zygotes at 5 hpi. By 10 hpi, all proteins were detected in most oocytes
      displaying two pronuclei. Nucleolar protein localization was exclusive to or more
      abundant in one pronucleus up to 20 hpi; thereafter, the pattern was more evenly
      distributed. Fibrillarin, nucleophosmin, nucleolin, UBF, and Pol I are present in
      the nuclei of growing and fully grown bovine oocytes until ONBD. They reappear at
      the late telophase stage of meiosis II and continue to be present up to the first
      mitotic division of embryo development.

PMID- 11319161
TI  - Modulation of potassium current characteristics in human myometrial smooth muscle
      by 17beta-estradiol and progesterone.
AB  - The K(+) channel currents are important modulators of smooth muscle membrane
      potential and excitability. We assessed whether voltage-gated K(+) currents from
      human myometrium are regulated by placental steroid hormones during pregnancy and
      labor. Pregnant human myometrial cells were isolated from samples obtained at
      cesarean section. Primary cultured cells were treated with 100 nM 17beta
      estradiol, 1 microM progesterone, or both hormones in combination for 24 h. Acute
      effects of the two hormones were also determined. The K(+) currents were recorded
      using the standard whole-cell, patch-clamp technique. Primary cultures possessed
      both delayed rectifier (I(KV)) and A-like (I(KA)) voltage-gated K(+) currents.
      The 24-h 17beta-estradiol treatment caused a hyperpolarizing shift in the steady
      state inactivation of both I(KV) and I(KA). Progesterone treatment also shifted
      the inactivation of I(KA) and increased I(KV) amplitude by 60%-110%. Conversely,
      the combined treatment had no effect on these currents. Neither 17beta-estradiol
      (0.1-1 microM) nor progesterone (1-5 microM) had any effect on the K(+) current
      when applied acutely. These results show that 17beta-estradiol should inhibit
      myometrial K(+) channel activity, whereas progesterone is likely to have the
      opposite effect. These results are consistent with the respective procontractile
      and proquiescence roles for 17beta-estradiol and progesterone in human uterus
      during pregnancy.

PMID- 11319162
TI  - Muc1 and glycan expression in the oviduct and endometrium of a New World monkey,
      Cebus apella.
AB  - Cebus apella is a New World monkey that has a menstrual cycle of 18-23 days with
      implantation at approximately luteal Day 5. The aim of this study was to
      characterize by lectin- and antibody-labeling the distribution of Muc1 and
      associated glycans on the endometrial and oviductal epithelium during the luteal
      phase of the cycle. Endometrial histology showed a thin endometrium, with glands
      extending deeply into the myometrium. No obvious evidence of secretory
      differentiation in cells of either the superficial or the basal segments of
      glands could be obtained using a panel of antibodies and lectins that marked
      epithelial glycoprotein, and glycosylation changes observed in some other primate
      endometrial cycles were not observed in this study. Antibodies to human MUC1 were
      shown to cross-react with C. apella, and Muc1 was localized to the apical
      epithelial surfaces of both the endometrial and the tubal epithelium, with
      stronger expression in the latter. Again, no cyclic changes were noted.
      Antibodies specific to the isoform Muc1/Sec showed strong staining at the apical
      tubal epithelium, but no reactivity was detectable in the luminal epithelium of
      the uterus. This observation suggests differences between the two glycocalyces
      and could help to explain why C. apella embryos do not implant in this location.

PMID- 11319163
TI  - Impact of epididymal maturation on the tyrosine phosphorylation patterns
      exhibited by rat spermatozoa.
AB  - As mammalian spermatozoa migrate through the epididymis, they acquire
      functionality characterized by the potential to express coordinated movement and
      the competence to undergo capacitation. The mechanisms by which spermatozoa gain
      the ability to capacitate during epididymal transit are poorly understood. The
      purpose of this study was to investigate the impact of epididymal maturation on
      the signal transduction pathways regulating tyrosine phosphorylation, because
      this process is thought to be central to the attainment of a capacitated state
      and expression of hyperactivated motility. Western blot and immunocytochemical
      analyses demonstrated that epididymal maturation in vivo is associated with a
      progressive loss of phosphotyrosine residues from the sperm head. As cells pass
      from the caput to the cauda epididymis, tyrosine phosphorylation becomes confined
      to a narrow band at the posterior margin of the acrosomal vesicle. Epididymal
      maturation of rat spermatozoa was also associated with an acquired competence to
      respond to high levels of intracellular cAMP by phosphorylating tyrosine residues
      on the sperm tail. Immature caput spermatozoa were incapable of exhibiting this
      response, despite the apparent availability of cAMP and protein kinase A. These
      findings help to clarify the biochemical changes associated with the functional
      maturation of spermatozoa during epididymal transit.

PMID- 11319164
TI  - Diversification of cyclooxygenase-2-derived prostaglandins in ovulation and
      implantation.
AB  - Previous observations of ovulation and fertilization defects in cyclooxygenase-2
      (COX-2)-deficient mice suggested that COX-2-derived ovarian prostaglandins (PGs)
      participate in these events. However, the specific PG and its mode of action were
      unknown. Subsequent studies revealed that mice deficient in EP(2), a PGE(2)
      receptor subtype, have reduced litter size, apparently resulting from poor
      ovulation but more dramatically from impaired fertilization. Using a
      superovulation regimen and in vitro culture system, we demonstrate herein that
      the ovulatory process, not follicular growth, oocyte maturation, or
      fertilization, is primarily affected in adult COX-2- or EP(2)-deficient mice.
      Furthermore, our results show that in vitro-matured and -fertilized eggs are
      capable of subsequent preimplantation development. However, severely compromised
      ovulation in adult COX-2- or EP(2)-deficient mice is not manifested in immature
      (3-wk-old) COX-2- or EP(2)-deficient mice, suggesting that the process of
      ovulation is more dependent on PGs in adult mice. Although the processes of
      implantation and decidualization are defective in COX-2(-/-) mice, our present
      results demonstrate that these events are normal in EP(2)-deficient mice, as
      determined by embryo transfer and experimentally induced decidualization.
      Collectively, previous and present results suggest that whereas COX-2-derived
      PGE(2) is essential for ovulation via activation of EP(2), COX-2-derived
      prostacyclin is involved in implantation and decidualization via activation of
      peroxisome proliferator-activated receptor delta.

PMID- 11319165
TI  - Activation of the Akt/protein kinase B signaling pathway is associated with
      granulosa cell survival.
AB  - Follicles from the hen ovary that have been selected into the preovulatory
      hierarchy are committed to ovulation and rarely become atretic under normal
      physiological conditions. In part, this is attributed to the resistance of the
      granulosa layer to apoptosis. The present studies were conducted to evaluate the
      role of the phosphatidylinositol (PI) 3-kinase/Akt signaling pathway in hen
      granulosa cell survival and, by implication, follicle viability. Cloning of the
      chicken akt2 homologue revealed a high degree of amino acid homology to its
      mammalian counterparts within the catalytic domain, plus complete conservation of
      the putative Thr(308) and Ser(474) phosphorylation sites. Treatment of granulosa
      cells from the three largest preovulatory follicles with insulin-like growth
      factor (IGF)-I and, to a lesser extent, transforming growth factor (TGF)-alpha
      induces rapid phosphorylation of Akt, and such phosphorylation is effectively
      blocked by the PI 3-kinase-inhibitor LY294006. Serum withdrawal from cultured
      cells for 33-44 h initiates oligonucleosome formation, an indicator of apoptotic
      cell death, whereas cotreatment with IGF-I prevents this effect. Moreover,
      treatment of cultured cells for 20 h with LY294006 induces apoptosis. The
      potential for nonspecific cell toxicity following LY294006 treatment is
      considered unlikely because of the ability of either LH or 8-bromo cAMP
      cotreatment to block LY294006-induced cell death. Finally, both IGF-I and TGF
      alpha also activate mitogen-activated protein (MAP) kinase signaling, at least in
      part, through the phosphorylation of ERK: However, treatment with neither U0126
      nor PD98059 (inhibitors of MAP kinase kinase) induced cell death in cultured
      granulosa cells, despite the ability of each inhibitor to effectively block Erk
      phosphorylation. Taken together, these results provide evidence for a role of the
      Akt signaling pathway in promoting cell survival within the preovulatory follicle
      granulosa layer. In addition, the data indicate the importance of an alternative
      survival pathway mediated via gonadotropins and protein kinase A independent of
      Akt signaling.

PMID- 11319166
TI  - Molecular cloning of chicken vasoactive intestinal polypeptide receptor
      complementary DNA, tissue distribution and chromosomal localization.
AB  - Chicken vasoactive intestinal polypeptide receptor (VIPR) cDNA was cloned by the
      reverse transcription-polymerase chain reaction method using primers designed on
      the basis of other species of VIPR cDNA. The cDNA obtained was sequenced by the
      dideoxy-mediated chain-termination method. Of the 2227 nucleotides that were
      sequenced, 84, 855, and 1338 bases represent the 5'-untranslated region (UTR),
      the 3'-UTR, and the open reading frame that predicts a peptide of 446 amino
      acids. The cDNA of the chicken VIPR shows 65% and 60% homologies to human cDNA of
      VIP1 and VIP2 receptors, respectively. The clone had the expected similarity to
      highly conserved features of the other G protein-coupled receptors (GPCRs) such
      as six cysteine residues that are functionally important in the VIPR subfamily.
      In addition, the seven potential membrane-spanning domains characteristic of the
      family B group III GPCR superfamily and highly conserved motif within the third
      cellular loop between transmembrane regions 5 and 6. Northern blot hybridization
      analysis in this study indicated mRNA expression of VIPRs in the various tissues
      of the chicken. Strong signal was detected in the brain and anterior pituitary
      gland. High levels of VIPR mRNA in the brain was consistent with VIP-binding
      experiments and with the function of VIP in the brain as a neuroendocrine factor
      or neurotransmitter. Expression of VIPR was detected in the anterior pituitary
      gland of chick embryos. The expression of VIPR mRNA in the chick anterior
      pituitary gland may indicate a regulatory function of VIP on prolactin (PRL)
      production or PRL cell proliferation during embryogenesis. Chicken VIPR shows
      high homology with mammalian type I VIPR but, in some part, possesses similarity
      of amino acid sequence. Expression of VIPR in various tissues supports diverse
      functions for VIP in the chicken.

PMID- 11319167
TI  - ASPO Joseph W. Cullen Memorial Award Lecture. Bridging the clinical and public
      health perspectives in tobacco treatment research: scenes from a tobacco
      treatment research career.
AB  - This paper, delivered as the 2000 Joseph W. Cullen Memorial Award Lecture,
      reviews smoking cessation treatment research conducted over the past 15 years at
      the Center for Health Studies, Group Health COOPERATIVE: The research program
      includes assessment, treatment, and health services research that addressed four
      main questions: (a) What motivates people to quit smoking? (b) Are self-help
      interventions effective? (c) Can health care benefits impact the utilization of
      smoking cessation services? and (d) Does smoking cessation impact health care
      utilization and costs? In the area of motivation for smoking cessation, an
      intrinsic-extrinsic model of type of motivation for smoking cessation was used to
      develop and validate a reasons for quitting scale. Results from administration of
      the scale across different samples of smokers show that higher levels of
      intrinsic relative to extrinsic motivation predicts successful cessation. A
      series of five randomized trials of self-help interventions indicate that self
      help interventions accompanied by motivational feedback and/or outreach telephone
      counseling can be effective. However, the same interventions did not improve long
      term abstinence rates in non-volunteer samples of smokers. With regard to health
      care benefits, we find that full coverage of smoking cessation services improves
      the reach of proven interventions into the general population of smokers with no
      significant reductions in effectiveness. Furthermore, studies of smoking
      cessation and health care utilization find that, although quitters have higher
      initial costs, their costs go down at the same time that those of continuing
      smokers' begin to accelerate. Cessation appears to reverse a trajectory of higher
      health care costs.

PMID- 11319168
TI  - Physical activity and cancer prevention: from observational to intervention
      research.
AB  - The purpose of this review is to articulate how progress in epidemiological
      research on physical activity and cancer prevention can be made. This report
      briefly reviews the accumulated evidence for an etiological role of physical
      activity in the prevention of cancer of the colon, breast, prostate, testes,
      lung, endometrium, and ovary and summarizes the evidence for a causal association
      for each of these sites. The evidence for a causal association between physical
      activity and colon and breast cancers is found to be "convincing," for prostate
      cancer to be "probable," for lung and endometrial cancers to be "possible," and
      for testicular and ovarian cancers to be currently "insufficient" to make any
      definitive conclusions. The emerging literature on physical activity and cancer
      prevention intervention studies is presented, and an overview of the literature
      on physical activity intervention is also provided. Given the level of evidence
      that is currently available for the associations between physical activity and
      cancer, it is argued that for additional progress to be made in this field, there
      need to be intervention studies on physical activity and cancers of the colon and
      breast. For the remaining cancer sites, better designed observational
      epidemiological studies are needed that address the identified methodological
      limitations found in previous studies. These limitations include crude and
      incomplete physical activity assessment, lack of adequate control for confounding
      and effect modification, as well as a lack of consideration of the underlying
      biological mechanisms that are operative. This review concludes with detailed
      recommendations for future research in this field.

PMID- 11319169
TI  - The NAD(P)H:quinone oxidoreductase 1 gene polymorphism and lung cancer:
      differential susceptibility based on smoking behavior.
AB  - We conducted a hospital-based case-control study of 814 lung cancer patients and
      1123 controls to examine the association of the NAD(P)H: quinone oxidoreductase 1
      (NQO1) gene polymorphism with lung cancer susceptibility. Using PCR-RFLP
      genotyping assay techniques, we analyzed DNA samples to detect the variant forms
      of the NQO1 gene in exon 6 on chromosome 16q. We examined the relationship
      between lung cancer odds and NQO1 genotypes after adjusting for age, gender, and
      smoking behavior using generalized additive modeling. We found no overall
      association between NQO1 genotypes and lung cancer susceptibility, regardless of
      age, gender, family history of cancer, or histological cell type. However, our
      data demonstrated that in both former and current smokers, there was an
      association between NQO1 genotypes and lung cancer susceptibility that was
      dependent upon cigarette smoking duration and smoking intensity. For both current
      and former smokers, smoking intensity was more important in predicting cancer
      risk than smoking duration for all of the genotypes. Among former smokers,
      individuals with the T/T genotype were predicted to have a greater cancer risk
      than those with the C/C genotype for smoking durations up to 37 years. The
      predicted cancer risk for former smokers with the C/T versus T/T genotype
      depended on both smoking intensity and smoking duration. Our results support the
      concept that differential susceptibility to lung cancer is a function of both an
      inheritable trait in NQO1 metabolism and individual smoking characteristics.

PMID- 11319170
TI  - Modulation of proliferating cell nuclear antigen in the bronchial epithelium of
      smokers.
AB  - Clinical chemoprevention trials seek to intervene in the carcinogenic process to
      suppress, reverse, or delay the development of invasive cancer. Dysregulated cell
      growth is a hallmark of epithelial carcinogenesis, and proliferating cell nuclear
      antigen (PCNA) is a marker of dysregulated proliferation that is highly expressed
      in non-small cell lung cancers. Squamous metaplasia of the bronchial epithelium
      is found in chronic smokers and has been considered an early premalignant change.
      To evaluate the effect of 13-cis-retinoic acid (13-cRA) on PCNA modulation, we
      evaluated PCNA expression in a total of 706 bronchial biopsy specimens from
      histologically normal, hyperplastic, metaplastic, and dysplastic bronchial
      tissues obtained from 86 healthy smokers at baseline, of whom 69 subjects had
      completed 6 months of treatment on a randomized placebo-controlled
      chemoprevention trial of 13-cRA and had repeat bronchoscopic biopsies. PCNA
      expression was evaluated with respect to bronchial metaplasia and as an
      intermediate end point for response in the trial. In the bronchial biopsies
      obtained from six standardized pretreatment and posttreatment sites, high PCNA
      expression correlated significantly with more advanced histological grade (P <
      0.001). Furthermore, smoking cessation during therapy correlated well with
      reduced PCNA expression (P = 0.006), although multivariate analysis indicated
      that this reduction in PCNA expression was associated with the reversal of
      squamous metaplasia. The level of PCNA expression appeared to correlate with the
      level of epidermal growth factor receptor expression both at baseline and at 6
      months. In those patients who ceased smoking during the intervention, the 13-cRA
      also appeared to be more effective than placebo in reducing PCNA expression (P =
      0.034 in all of the layers; P = 0.026 in basal layers). The efficacy of 13-cRA in
      the down-regulation of PCNA in quitters was independent of baseline PCNA
      expression levels. Our study demonstrated that increased PCNA expression was
      associated with histological progression from normal bronchial epithelium to
      squamous metaplasia and dysplasia. The modulation of PCNA by 13-cRA in patients
      who quit smoking suggests a potentially important role for regulating this
      proliferation marker in retinoid chemoprevention studies of former smokers.

PMID- 11319171
TI  - Chromosome polysomy and histological characteristics in oral premalignant
      lesions.
AB  - Head and neck tumorigenesis has been postulated to represent a multistep process
      driven by the accumulation of carcinogen-induced genetic changes throughout the
      exposed tissue field. To better explore this genetic instability process at the
      tissue level, 59 regions within 26 biopsy tissue specimens from individuals with
      oral leukoplakia have been subjected to chromosome 9 in situ hybridization
      analysis, and the degree of chromosome instability was related to known
      clinical/pathological parameters associated with tumor risk. Whereas chromosome
      indices were similar between high-risk lesion sites and low-risk lesion sites,
      high-risk lesions showed higher levels of chromosome polysomy than did low-risk
      sites [median PIs (polysomy indices), 2.1 versus 1.4, respectively]. Similarly,
      dysplastic regions showed significantly higher chromosome polysomy levels than
      hyperplastic regions (median PIs, 2.4 versus 1.5, respectively). Interestingly,
      however, hyperplastic regions in the same biopsy as dysplastic regions showed two
      times higher polysomy levels than those in biopsies without dysplasia (median
      PIs, 2.6 versus 1.3, respectively), suggesting that chromosome polysomy
      determinations provide a field measurement for the degree of ongoing genetic
      insult. Finally, chromosome polysomy tended to persist or increase in the
      superficial epithelial layers in regions showing koilocytosis, whereas their
      frequency decreased in nonkoilocytotic regions, suggesting that epigenetic
      factors may serve to perpetuate the levels of genetically unstable cells in the
      epithelium. These results provide direct support for the field cancerization
      process and suggest that measurements of genetic instability might provide
      additional biological information beyond histology and lesion site
      characteristics in the assessment of head and neck cancer risk.

PMID- 11319172
TI  - Cigarette smoking increases risk for breast cancer in high-risk breast cancer
      families.
AB  - Most epidemiological studies of cigarette smoking and breast cancer have failed
      to demonstrate a strong association. Only one study has been performed on women
      at high genetic risk, and smoking was reported to be a protective factor. To
      further explore this observation, we examined the association of cigarette
      smoking with the risk of breast cancer in a historical cohort study of high-risk
      breast cancer families. A total of 426 families ascertained through a consecutive
      series of breast cancer patients (probands) between 1944 and 1952 were followed
      through 1996. Occurrence of breast cancer and detailed smoking histories for
      sisters, daughters, granddaughters, nieces, and marry-ins were obtained through
      telephone interviews between 1991 and 1996. Cox proportional hazards regression,
      accounting for age, birth cohort, and other risk factors, was used to calculate
      relative risks and 95% confidence intervals (CIs) of breast cancer. All of the
      models were constructed within strata defined by relationship to the index case
      (proband), with nonsmokers designated as the referent group. Of the 426 families
      in the cohort, 132 had at least three incident breast and/or ovarian cancers in
      the biological relatives at the end of the follow-up period. Among sisters and
      daughters in these 132 high-risk families, those who ever smoked were at 2.4-fold
      increased risk of breast cancer (95% CI, 1.2-5.1) relative to never-smokers. No
      association between breast cancer and smoking was observed among nieces and
      granddaughters of probands or among marry-ins. When the analysis was restricted
      to 35 families at highest genetic risk (each containing five breast and/or
      ovarian cancers), smoking became an even stronger risk factor. Among sisters and
      daughters, ever-smokers were at 5.8-fold greater risk than nonsmokers (95% CI,
      1.4-23.9). Among nieces and granddaughters, the risk of breast cancer associated
      with smoking was increased 60% (95% CI, 0.8-3.2). These results suggest that
      smoking may increase risk for breast cancer in families with multiple cases of
      breast or ovarian cancer, especially those with the strongest apparent familial
      predisposition.

PMID- 11319173
TI  - Comparisons of two breast cancer risk estimates in women with a family history of
      breast cancer.
AB  - There is an increasing need for accurate prediction methods of assessing
      individual risk for breast cancer for both clinical and research purposes. The
      purpose of this study is to compare the Gail and Claus model risk estimates of
      breast cancer among women with a family history of breast cancer. This study
      presents risk estimates from two models of breast cancer risk in 491 women 18 to
      74 years of age with a family history of breast cancer who were recruited to risk
      counseling clinical trials in Seattle, Washington between 1996 and 1997. These
      trials included women from the general population and additional samples of
      Ashkenazi Jewish, African-American, and lesbian women. We estimated and compared
      lifetime (to age 79) and 5-year risk for developing breast cancer using the
      National Surgical Adjuvant Breast and Bowel Project adaptation of the Gail model
      and the Claus model. About one-quarter of participants fell into the Gail "high"
      risk category (> or =1.7% risk of developing breast cancer in the next 5 years).
      The average lifetime risk was estimated at 13.2% by the Gail model and 11.2% by
      the Claus model. Estimates from the two models were moderately and positively
      correlated (r = 0.55) with the Gail model yielding a higher estimate than the
      Claus model for most participants. If women with a family history of breast
      cancer are being counseled regarding decisions on genetic testing, tamoxifen use,
      or other preventive measures, presenting both Claus and Gail estimates may be the
      best option.

PMID- 11319174
TI  - Serum enterolactone and risk of breast cancer: a case-control study in eastern
      Finland.
AB  - Phytoestrogens have been linked to a risk of breast cancer. The main
      phytoestrogens in the Finnish diet are lignans, and enterolactone is
      quantitatively the most important circulating lignan. The purpose of this study
      was to examine the association between serum enterolactone and risk of breast
      cancer in Finnish women. The subjects were participants of the Kuopio Breast
      Cancer Study: This analysis concerns 194 breast cancer cases (68 premenopausal
      and 126 postmenopausal) who entered the study before diagnosis and 208 community
      based controls. They completed a validated food frequency questionnaire referring
      to the previous 12 months and gave serum samples before the examinations. The
      measurement of serum enterolactone was performed by time-resolved
      fluoroimmunoassay. The statistical analyses were done by the logistic regression
      method. The mean serum enterolactone concentration was 20 nmol/l for the cases
      and 26 nmol/l for the controls (P 0.003). The mean serum enterolactone
      concentration in the lowest quintile was 3.0 nmol/l and 54.0 nmol/l in the
      highest. The odds ratio in the highest quintile of enterolactone values adjusted
      for all of the known risk factors for breast cancer was 0.38 (95% confidence
      interval,0.18-0.77; P for trend, 0.03). The inverse association between serum
      enterolactone and risk of breast cancer was seen both among premenopausal and
      postmenopausal women. High enterolactone level was associated with higher
      consumption of rye products and tea and higher intake of dietary fiber and
      vitamin E compared with those with low serum enterolactone values. Serum
      enterolactone level was significantly inversely associated with risk of breast
      cancer.

PMID- 11319175
TI  - Body mass index, height, and prostate cancer mortality in two large cohorts of
      adult men in the United States.
AB  - Body weight and height have both been associated consistently with postmenopausal
      breast cancer but less consistently with prostate cancer. The present study
      examined the relationship between body mass index (BMI), height, and death from
      prostate cancer in two large American Cancer Society cohorts. Men in the study
      were selected from the male participants in Cancer Prevention Study I (CPS-I;
      enrolled in 1959 and followed through 1972) and Cancer Prevention Study II (CPS
      II; enrolled in 1982 and followed through 1996). After exclusions, 1,590 prostate
      cancer deaths remained among 381,638 men in CPS-I and 3,622 deaths among 434,630
      men in CPS-II. Cox proportional hazards modeling was used to compute rate ratios
      (RR) and to adjust for confounders. Prostate cancer mortality rates were
      significantly higher among obese (BMI, > or =30) than nonobese (BMI, <25) men in
      both cohorts [adjusted RR, 1.27; 95% confidence interval (CI), 1.04-1.56 in CPS
      I; RR, 1.21; 95% CI, 1.07-1.37 in CPS-II]. Prostate cancer mortality rates in the
      CPS-I cohort were lowest for the shortest men (RR, 0.80; 95% CI, 0.63-1.03 for
      men <65 inches versus 65-66 inches) and highest for the tallest men (RR, 1.39;
      95% CI, 1.11-1.74 for men > or =73 inches tall versus 65-66 inches). Rates
      remained constant among men 65-72 inches tall. No association between height and
      prostate cancer mortality was observed in the CPS-II cohort (RR, 1.03; 95% CI,
      0.82-1.29 for men > or =75 versus 65-66 inches). These results support the
      hypothesis that obesity increases risk of prostate cancer mortality. Decreased
      survival among obese men may be a likely explanation for this association.

PMID- 11319176
TI  - Associations between ERCC2 polymorphisms and gliomas.
AB  - Xeroderma pigmentosum complementation group D/excision repair cross-complementing
      in rodents 2 (ERCC2) encodes a protein that is part of the nucleotide excision
      repair pathway and the transcription factor IIH transcription complex. Mutations
      in this gene have been shown to cause three distinct clinical diseases including
      xeroderma pigmentosum, Cockayne syndrome, and trichothiodystrophy. Several ERCC2
      polymorphisms, the effects of which on gene function are not known, have been
      described. To investigate whether constitutive sequence variations might be
      associated with adult onset gliomas, blood specimens from a case-control study
      (187 cases and 169 controls) were genotyped for seven previously described
      polymorphisms (R156R, I199M, H201Y, D312N, A575A, D711D, and K751Q). A novel
      R616C polymorphism was also identified. Cases were significantly more likely than
      controls to be homozygous for the silent AA variant at codon 156 (odds ratio,
      2.3; 95% confidence interval, 1.3-4.2). Although this was observed for patients
      in each of three histological subgroups of cases, (glioblastoma multiforme,
      astrocytoma, and oligoastrocytoma) compared with controls, the association was
      strongest for patients with oligoastrocytoma (odds ratio, 3.2; 95% confidence
      interval, 1.1-9.5). In contrast, cases were somewhat less likely than controls to
      carry variants at D312N, D711D, and K751Q, but not significantly so overall or
      for any subgroup after adjustment for age and gender. Individuals with variant
      nucleotides at D312N, D711D, and K751Q were significantly more likely to carry a
      variant at another of those three codons and less likely to carry a variant
      nucleotide at R156R, regardless of case or control status. Although the pattern
      of association observed here is consistent with a role of ERCC2 variants in the
      prevention or causation of glioma, these results are also consistent with the
      possibility that another gene linked to ERCC2 may be involved. This seems
      especially so because the strongest association was observed with a silent
      nucleotide variation.

PMID- 11319177
TI  - Blood transfusions and risk of non-Hodgkin's lymphoma subtypes and chronic
      lymphocytic leukemia.
AB  - Allogeneic blood transfusion has been suggested as a risk factor for non
      Hodgkin's lymphoma (NHL), possibly specific to certain NHL subtypes, or chronic
      lymphocytic leukemia (CLL). Self-reported transfusion history and risk of NHL
      subtypes and CLL were examined in a cohort of 37,934 older Iowa women, using data
      from a questionnaire mailed in 1986. Through 1997, 229 cases of NHL and 57 cases
      of CLL in the cohort were identified through linkage to the Iowa Surveillance,
      Epidemiology and End Results Cancer REGISTRY: Women who reported ever receiving a
      blood transfusion were at increased risk for all NHLs [age adjusted relative risk
      (RR), 1.6; 95% confidence interval (CI), 1.2-2.1). On the basis of the Working
      Formulation classification, blood transfusion was positively associated with low
      grade NHL (RR, 2.7; 95% CI, 1.7-4.5) but not with intermediate-grade NHL (RR,
      1.1; 95% CI, 0.7-1.6); there were only 8 cases of high-grade NHL. Blood
      transfusion was positively associated with follicular (RR, 2.8; 95% CI, 1.6-5.1)
      and small lymphocytic (RR, 3.4; 95% CI, 1.5-7.9) NHL subtypes but not with
      diffuse NHL (RR, 1.0; 95% CI, 0.7-1.5). There was also a positive association
      with CLL (RR, 1.7; 95% CI, 1.0-3.0). Finally, transfusion was associated with
      nodal (RR, 1.8; 95% CI, 1.3-2.5) but not extranodal (RR, 1.2; 95% CI, 0.7-2.1)
      NHL. Further adjustment for marital status, farm residence, diabetes, alcohol
      use, smoking, and red meat and fruit consumption did not alter these
      associations. In conclusion, prior blood transfusion was associated with NHL and
      CLL, and the strongest associations were seen for low-grade NHL, particularly
      follicular and small lymphocytic NHL.

PMID- 11319178
TI  - Levels of malondialdehyde-deoxyguanosine in the gastric mucosa: relationship with
      lipid peroxidation, ascorbic acid, and Helicobacter pylori.
AB  - Helicobacter pylori infection is associated with elevated gastric mucosal
      concentrations of the lipid peroxidation product malondialdehyde and reduced
      gastric juice vitamin C concentrations. Malondialdehyde can react with DNA bases
      to form the mutagenic adduct malondialdehyde-deoxyguanosine (M(1)-dG). We aimed
      to determine gastric mucosal levels of M(1)-dG in relation to H. pylori infection
      and malondialdehyde and vitamin C concentrations. Patients (n = 124) attending
      for endoscopy were studied. Levels of antral mucosal M(1)-dG were determined
      using a sensitive immunoslot-blot technique; antral mucosal malondialdehyde was
      determined by thiobarbituric acid extraction, and gastric juice and antral
      mucosal ascorbic acid and total vitamin C were determined by high-performance
      liquid chromatography. Sixty-four H. pylori-positive patients received
      eradication therapy, and endoscopy was repeated at 6 and 12 months. Levels of
      M(1)-dG did not differ between subjects with H. pylori gastritis (n = 85) and
      those with normal mucosa without H. pylori infection (n = 39; 56.6 versus 60.1
      adducts/10(8) bases) and were unaffected by age or smoking habits.
      Malondialdehyde levels were higher (123.7 versus 82.5 pmol/g; P < 0.001), gastric
      juice ascorbic acid was lower (5.7 versus 15.0 micromol/ml; P < 0.001), and
      antral mucosal ascorbic acid was unchanged (48.0 versus 42.7 micromol/g) in H.
      pylori gastritis compared with normal mucosa. Multiple regression analysis
      revealed that M(1)-dG increased significantly with increasing levels of
      malondialdehyde, antral ascorbic acid, and total antral vitamin C. M(1)-dG levels
      were unchanged 6 months (63.3 versus 87.0 adducts/10(8) bases; P = 0.24; n = 38)
      and 12 months (66.7 versus 77.5 adducts/10(8) bases; P = 0.8; n = 13) after
      successful eradication of H. pylori. M(1)-dG thus is detectable in gastric
      mucosa, but is not affected directly by H. pylori.

PMID- 11319179
TI  - Genetic and nongenetic factors associated with variation of plasma levels of
      insulin-like growth factor-I and insulin-like growth factor-binding protein-3 in
      healthy premenopausal women.
AB  - Circulating levels of insulin-like growth factor-I (IGF-I) and insulin-like
      growth factor-binding protein 3 (IGFBP-3) vary considerably between normal
      individuals. Recent epidemiological studies have provided evidence that these
      levels are predictive of risk of several common cancers. To evaluate possible
      sources of variation of the levels of circulating IGF-I and IGFBP-3 in females,
      we studied specific candidate genetic and nongenetic factors in 311 nulliparous,
      premenopausal Caucasian women, 17-35 years of age. Women who used oral
      contraceptives (OC) had reduced levels of IGF-I (269 versus 301 ng/ml; P = 0.001
      adjusted for age) and increased levels of IGFBP-3 (4213 versus 4009 ng/ml; P =
      0.002, adjusted for age) compared with nonusers. The ratio of IGF-I:IGFBP-3 was
      associated with the dose of estrogen contained in the OC (P(trend) = 0.006,
      adjusted for age). We identified a novel single bp polymorphism in the promoter
      region of the gene encoding IGFBP-3. This polymorphism was related to the level
      of IGFBP-3 in the circulation. Mean IGFBP-3 levels were 4390, 4130, and 3840
      ng/ml for the AA, AC, and CC genotypes, respectively (P(trend) = 0.006, adjusted
      for age and OC use). We observed no effect of a recently described polymorphism
      in the promoter region of the gene encoding IGF-I on the plasma IGF-I level, but
      there was evidence for a modifying effect of this locus on the influence of OC on
      the IGF-I level. Our results support the view that circulating IGF-I levels and
      IGFBP-3 levels are complex traits and are influenced by a number of interacting
      genetic and nongenetic factors.

PMID- 11319180
TI  - Interactions of selenium compounds with other antioxidants in DNA damage and
      apoptosis in human normal keratinocytes.
AB  - Selenite (SeL) or selenomethionine (SeM) are the most common selenium (Se)
      compounds taken as dietary antioxidants to reduce oxidative stress. Because the
      public may frequently supplement Se compounds at high doses, the possible pro
      oxidant effect of Se becomes a concern. SeL and SeM have entirely different
      pharmacokinetic effects based on dose-related cytotoxicity. Our laboratory has
      shown previously that high doses of SeL resulted in cytotoxicity and induction of
      8-hydroxydeoxyguanosine (8-OHdG) in DNA of primary human keratinocytes (NHK),
      compared with those treated with the same doses of SEM: Besides Se compounds,
      other dietary antioxidants, such as vitamin (Vit) C or Vit E, are often
      supplemented and taken together with Se compounds. However, the cellular effects
      of these interactions of Se with antioxidants are still unknown. In addition,
      copper is commonly present in drinking water, food, soil, or the environment to
      increase the possibility of subchronic toxicity. Copper has been shown to inhibit
      SeL-induced cytotoxicity and apoptosis in human colonic carcinoma cells. The
      present study was designed to investigate the interactive effects of SeL or SeM
      plus Vit C, trolox (a water-soluble Vit E), or copper sulfate (CuSO(4)) on cell
      viability and induction of 8-OHdG adduct formation in DNA of NHK. NHK cells were
      treated with no Se, SeL (126.6 microM Se), or SeM (316.6 microM Se) plus two
      doses each of Vit C (2.27 and 4.45 microM), trolox (40 and 80 microM), or CuSO(4)
      (7.85 and 15.7 microM) for 24 h. Coincubation of Vit C or CuSO(4) with SeL
      appeared to protect NHK against SeL-induced cytotoxicity. However, synergistic
      effects were observed between SeL and trolox resulting in enhanced cytotoxicity.
      On the other hand, SeM + Vit C, SeM + trolox, and SeM + CuSO(4) did not affect
      cell viability. In the absence of Se supplementation, Vit C, trolox, or CuSO(4)
      alone did not induce 8-OHdG adduct formation, regardless of dose. When NHK cells
      were coincubated with SeL (126.6 microM Se) and Vit C or CuSO(4), they protected
      NHK from SeL-induced DNA damage with a reduction in 8-OHdG generation. In
      contrast, treatment of SeL + trolox elevated generation of 8-OHDG: Furthermore,
      treatments of SeM plus trolox or CuSO(4) elevated 8-OHdG adduct formation. In
      terms of apoptosis measured as internucleosomal DNA fragmentation, copper
      protected NHK against SeL-induced apoptosis in cultured NHK. These data suggest
      that the use of CuSO(4) may play a protective role in SeL-induced cytotoxicity,
      DNA oxidative damage, and apoptosis and that there may be potentially deleterious
      interactions among common high-dose antioxidant supplements taken by the public.

PMID- 11319181
TI  - Effects of novel phenylretinamides on cell growth and apoptosis in bladder
      cancer.
AB  - Superficial bladder cancer is a major target for chemoprevention. Retinoids are
      important modulators of epithelial differentiation and proliferation and are
      effective in the treatment and prevention of several epithelial cancers. One
      class of compounds, the retinamides, is structurally similar to other retinoids
      but have the added feature of being potent apoptosis inducers. Among these,
      fenretinide (N-[4-hydroxyphenyl]retinamide), or 4HPR, has promise for bladder
      cancer chemoprevention and is currently under Phase III study in this setting. In
      addition to 4HPR, there are several new structurally related phenylretinamides
      bearing hydroxyl, carboxyl, or methoxyl residues on carbons 2, 3, and 4 of the
      terminal phenylamine ring [designated N-(2-hydroxyphenyl)retinamide, N-(3
      hydroxyphenyl)retin amide, N-(2-carboxyphenyl)retin- amide, N-(3
      carboxyphenyl)retin amide, N-(4-carboxy- phenyl)retinamide, and N-(4
      methoxyphenyl)retinamide, respectively]. The objective of this study was to
      compare the growth inhibitory and apoptotic effects of these phenylretinamides
      with 4HPR in human bladder transitional cell cancer-derived cell lines of varying
      histological grade (RT4, grade 1; UM-UC9 and UM-UC10, grade 3; and UM-UC14, grade
      4) by cell counting, cell cycle fluorescence-activated cell sorter analysis and a
      dual stain apoptosis assay. All of the seven phenylretinamides reduced cell
      number, altered the cell cycle distribution, and induced apoptosis when
      administered at a concentration of 10 microM, which is within the
      pharmacologically achievable range. Although the relative potencies of the
      phenylretinamides varied depending on the cell line, N-(3-hydroxy phenyl)retin-
      amide was the most active with significantly greater growth inhibition than 4HPR
      in all of the four cell lines. These in vitro findings warrant further study of
      these novel phenylretinamides, which may have potential as preventive or
      therapeutic agents in transitional cell cancer.

PMID- 11319182
TI  - Polymorphisms of methylene-tetrahydrofolate reductase and risk of lung cancer: a
      case-control study.
AB  - Previous studies have suggested that low folate intake is associated with
      increased risk of lung cancer. Methylene-tetrahydrofolate reductase (MTHFR) is
      one of the enzymes involved in folate metabolism and is thought to influence DNA
      methylation and nucleotide synthesis. MTHFR is highly polymorphic, and the
      variant genotypes result in decreased MTHFR enzyme activity and lower plasma
      folate level. Therefore, we hypothesized that these variant genotypes may play a
      role in the etiology of lung cancer. To test this hypothesis, we investigated the
      association between two common MTHFR polymorphisms (C677T and A1298C) and risk of
      lung cancer in a non-population-based case-control study of 550 histologically
      confirmed lung cancer cases and 554 healthy controls. The subjects were non
      Hispanic whites, and the controls were frequency-matched to the cases by age (+
      or -5 years), sex, and smoking status (ever or never). Folate intake and alcohol
      consumption were estimated from a self-administered food-frequency questionnaire.
      The cases consumed significantly less folate (162 microg/day/1000 kcal) than the
      controls did (172 microg/day/1000 kcal; P = 0.033). However, we found no evidence
      for an association between the MTHFR C677T and A1298C polymorphisms and risk of
      lung cancer in either all of the subjects or the low folate intake subgroup; nor
      did we find evidence for an interaction between these two MTHFR polymorphisms and
      dietary folate intake or alcohol use. In multivariate logistic regression
      analysis, the adjusted odds ratios and 95% confidence intervals for MTHFR C677T
      were 1.1 (0.8-1.4) for 677CT versus 677CC wild type and 1.1 (0.7-1.7) for 677TT
      versus 677CC, and for MTHFR A1298C, they were 1.0 (0.8-1.3) for 1298AC versus
      1298AA wild type and 1.1 (0.7-1.8) for 1298CC versus 1298AA. These results
      suggest that the MTHFR C677T and A1298C polymorphisms by themselves do not play
      an important role in the etiology of lung cancer.

PMID- 11319183
TI  - Association between the dopamine D2 receptor A2/A2 genotype and smoking behavior
      in the Japanese.
AB  - For the study presented here, we investigated possible links between the dopamine
      D2 receptor (DRD2) TaqIA genotype (DRD2*A) and smoking behavior in a total of 332
      Japanese individuals. For the first time, functional insertion/deletion
      polymorphism (-141C Ins/Del) in the DRD2 promoter was also examined in relation
      to smoking behavior. The distribution of the DRD2*A genotype was significantly
      different among current, former, and never-smokers (P = 0.001; chi(2) test), and
      smoking appeared to be associated with the DRD2 A2/A2 genotype, showing marked
      contrast to previous reports for non-Hispanic whites in the United STATES:
      Multivariate logistic regression analysis incorporating age, sex, genotype, and
      smoking status as variables revealed that DRD2 A2/A2 genotype was significantly
      associated with an increased risk of predisposition to smoking behavior in the
      Japanese (odds ratio, 3.680; 95% confidence interval, 1.499-9.052). In contrast,
      such an increased risk was not observed in terms of association with the -141C
      Ins/Del polymorphism. These findings suggest an association of the DRD2*A
      genotype with an increased risk of being predisposed to smoking behavior in the
      Japanese and suggest the possible existence of ethnic group-specific differences,
      which warrant additional studies on the underlying molecular mechanism.

PMID- 11319184
TI  - Sources of elevated serum androgens in postmenopausal women who develop breast
      cancer.
AB  - Postmenopausal women with elevated serum androgens are at an increased risk of
      breast cancer. High dehydroepiandrosterone sulfate concentrations in these women
      suggest increased adrenal secretion. Both the adrenals and ovaries could
      contribute to elevated concentrations of androstenedione (Delta4A). 11beta
      Hydroxyandrostenedione (11betaOHA) is elevated, and the Delta4A:11betaOHA ratio
      is depressed when the adrenals are the primary source of elevated Delta4A in
      women. Conversely, Delta4A:11betaOHA is elevated when the ovaries are the primary
      source. We prospectively evaluated associations of serum 11betaOHA and
      Delta4A:11betaOHA with breast cancer in the Columbia, Missouri Serum Bank to
      identify the source of elevated Delta4A related to risk. Fifty-three
      postmenopausal women who were not taking estrogens when they donated blood and
      were diagnosed with breast cancer up to 10 years later (median, 2.9 years) served
      as cases. Two controls, who were also postmenopausal and not taking estrogens,
      were matched to each case on age, date, and time of blood collection. Serum
      Delta4A concentration was significantly (trend P = 0.02) positively associated
      with breast cancer risk. Adjusted risk ratios for women in the lowest to highest
      tertiles were 1.0, 1.6, and 2.4 [95% confidence interval (CI), 0.9-6.5]. However,
      neither 11betaOHA concentration nor Delta4A:11betaOHA was related to risk.
      Comparable risk ratios were 1.0, 1.2, and 1.4 (95% CI, 0.5-3.6) for 11betaOHA and
      1.0, 1.2, and 1.2 (95% CI, 0.4-3.5) for Delta4A:11betaOHA. Our results suggest
      that neither the ovaries nor adrenals are the predominant source of elevated
      serum Delta4A in postmenopausal women who develop breast cancer, but rather both
      may contribute.

PMID- 11319185
TI  - PTEN polymorphism (IVS4) is not associated with risk of prostate cancer.

PMID- 11319186
TI  - Risk of brain glioma not associated with cigarette smoking or use of other
      tobacco products in Iowa.

PMID- 11319187
TI  - Correspondence re: E. Hawk, et al., Male pattern baldness and clinical prostate
      cancer in the epidemiologic follow-up of the First National Health and Nutrition
      Examination Survey. Cancer Epidemiol.Biomark. Prev., 9: 523-527, 2000.

PMID- 11319188
TI  - Correspondence re: Cummings et al., Consumer perception of risk associated with
      filters contaminated with glass fibers. Cancer Epidemiol. Biomark. Prev., 9: 977
      979, 2000.

PMID- 11319189
TI  - Cholesterol sulfate: a new adhesive molecule for platelets.
AB  - BACKGROUND: Cholesterol 3-sulfate is present on a variety of cells and in human
      LDL, and it has been found in atherosclerotic lesions of human aorta. Its precise
      biological role has not yet been described. METHODS AND RESULTS: In this study,
      we investigated the interaction of platelets with cholesterol sulfate. Platelets
      adhered in a concentration-dependent and saturable manner to cholesterol sulfate
      but did not adhere to cholesterol, cholesterol acetate, estrone sulfate, or
      dehydroepiandrosterone sulfate, suggesting that the specificity of this
      interaction is determined not only by the cholesterol moiety but also by the
      sulfate group. This adhesion did not increase after platelet activation, and it
      was not cation-dependent. Soluble cholesterol sulfate inhibited adhesion in a
      concentration-dependent manner. However, antibodies against glycoprotein Ib,
      glycoprotein IIb/IIIa, CD36, P-selectin, von Willebrand factor, or thrombospondin
      had no significant effect on platelet adhesion to cholesterol sulfate. Perfusion
      of whole blood in a parallel-plate flow chamber resulted in the rapid and
      progressive adhesion of platelets to cholesterol sulfate but not to cholesterol
      acetate or estrone sulfate. CONCLUSIONS: Cholesterol sulfate supports platelet
      adhesion and may be one of the factors determining the prothrombotic potential of
      atherosclerotic lesions.

PMID- 11319190
TI  - Preload induces troponin I degradation independently of myocardial ischemia.
AB  - BACKGROUND: Although global ischemia induces troponin I (TnI) degradation,
      regional ischemia does not. We hypothesized that this disparity is related to
      preload-induced proteolysis, which varies as a function of the amount of
      myocardium at risk of ischemia. METHODS AND RESULTS: Isolated rat hearts were
      buffer-perfused at controlled levels of preload. Increasing preload to 25 mm Hg
      in the absence of ischemia produced pronounced TnI degradation (27 kDa versus 31
      kDa bands: 16.4 +/- 3.6% versus 4.7 +/- 1.9% in immediately excised controls,
      P<0.05). TnI degradation could be blocked by preventing the activation of
      endogenous calpains with 25 micromol/L calpeptin (4.3 +/- 0.6%). This improved
      function, with left ventricular systolic pressure increasing from 103 +/- 4 mm Hg
      to 137 +/- 7 mm Hg (P<0.05). Eliminating elevations in preload after global
      ischemia-induced stunning also prevented TnI degradation. CONCLUSIONS: Calpain
      mediated TnI proteolysis can be dissociated from stunning and arises from
      elevations in preload rather than ischemia. This raises the possibility that
      ongoing preload-induced TnI degradation could impair myocardial function long
      term.

PMID- 11319191
TI  - State of complementary and alternative medicine in cardiovascular, lung, and
      blood research: executive summary of a workshop.
AB  - The National Heart, Lung, and Blood Institute and the National Center for
      Complementary and Alternative Medicine recently cosponsored a workshop on the use
      of complementary and alternative medicine (CAM) in cardiovascular, lung, and
      blood research. In view of the increasing use of CAM by the general public, it is
      imperative to promote credible research by the established biomedical community.
      The goal of this workshop was to enhance the exchange of information and ideas
      between alternative medicine practitioners and scientists in cardiovascular,
      lung, and blood research and to foster collaborative research among these
      researchers. The workshop focused on 5 areas of research, including a historical
      and cultural perspective of CAM, methodological issues in clinical trials, herbal
      medicine, chelation therapy, mind/body (meditation) therapy, and acupuncture. CAM
      has become widely used without rigorously proven efficacy and safety. To protect
      the public, it was recommended that the fundamental mechanistic research for
      these CAM approaches be vigorously pursued and that any large-scale clinical
      trial be carefully executed to avoid any waste of resources and any unnecessary
      risk. It was felt that standardization of botanical products and procedure-based
      CAM intervention, such as acupuncture and meditation, is essential for meaningful
      basic and clinical research. Although botanical products properly consumed are
      perceived as generally safe, potential herb-drug interactions are a major safety
      concern. Clearly, many challenges need to be addressed by the scientific
      community before the public can be assured of the proper use of CAM.

PMID- 11319192
TI  - Oral anticoagulant therapy during and after coronary angioplasty the intensity
      and duration of anticoagulation are essential to reduce thrombotic complications.
AB  - BACKGROUND: In the randomized Balloon Angioplasty and Anticoagulation Study
      (BAAS), the addition of oral anticoagulants to aspirin significantly reduced
      early and late events after coronary angioplasty. However, bleeding episodes were
      increased. The present report studied the intensity and the duration of
      anticoagulation as predictors of thrombotic and bleeding events. METHODS AND
      RESULTS: A total of 530 patients, 34% of whom received a stent, were treated with
      aspirin plus coumarins. Half of the patients were randomized to angiographic
      follow-up. The target international normalized ratio (INR) was 2.1 to 4.8 during
      angioplasty and 6-month follow-up. Thrombotic events were death, myocardial
      infarction, target lesion revascularization, and thrombotic stroke. Bleeding
      complications were hemorrhagic stroke, major extracranial bleeding, and false
      aneurysm. "Optimal" anticoagulation was defined as an INR in the target range for
      at least 70% of the follow-up time. There were 17 early thrombotic events (3.2%),
      7 early bleeding episodes (1.3%), and 10 false aneurysms (1.9%). The incidence
      rate for both early thrombotic and bleeding events was lowest in patients in the
      target range. A total of 61 late thrombotic events occurred (11.6%). Optimal
      anticoagulation was an independent predictor of late thrombotic events (relative
      risk, 0.33; 95% CI, 0.19 to 0.57) and was associated with a 0.21 mm (95% CI, 0.17
      to 0.42) larger vessel lumen at 6 months. Late bleeding episodes (1.4%) were
      lowest in patients in the target range. CONCLUSIONS: Coumarins started before
      coronary angioplasty with a target INR of 2.1 to 4.8 led to the lowest procedural
      event rate, without an increase in bleeding episodes. During follow-up, optimal
      anticoagulation was associated with a decrease in the incidence of late events by
      67% and a significant improvement in 6-month angiographic outcome.

PMID- 11319193
TI  - Relation of a common methylenetetrahydrofolate reductase mutation and plasma
      homocysteine with intimal hyperplasia after coronary stenting.
AB  - BACKGROUND: Hyperhomocysteinemia has been identified as an independent risk
      factor for coronary artery disease. Recent studies have shown that a common
      mutation (nucleotide 677 C-->T) in the methylenetetrahydrofolate reductase
      (MTHFR) gene may contribute to mild hyperhomocysteinemia and, therefore, to the
      incidence of coronary artery disease. No information exists, however, regarding
      the association between the mutation of the MTHFR gene or plasma homocysteine
      levels and morphological analysis of coronary atherosclerosis using intravascular
      ultrasound. METHODS AND RESULTS: To examine the potential influence of MTHFR
      genotype and homocysteine on coronaryarteries morphologically, we screened 62
      patients with 65 lesions that were treated with 93 Palmaz-Schatz stents. The
      plasma homocysteine levels in the patients with the TT genotype were not
      significantly higher than those in the patients with non-TT (CC+CT) genotypes
      (13.1 +/- 5.5 versus 11.5 +/- 3.1 mmol/L, P=0.16). Angiographic analysis showed
      that the percent diameter stenosis in the patients with the TT genotype was
      significantly greater than that in those with non-TT genotypes (43.7 +/- 17.8%
      versus 29.0 +/- 22.0%, P=0.015). Intravascular ultrasound analysis showed that
      the TT genotype was significantly associated with greater intimal hyperplasia
      area (5.70 +/- 1.94 versus 3.72 +/- 1.38 mm2, P=0.001). In multiple stepwise
      regression analysis, the number of the T alleles was the only independent
      predictor of intimal hyperplasia after intervention (r2=0.21, P=0.004).
      CONCLUSIONS: The homozygous mutant genotype of the MTHFR gene may increase the
      risk of in-stent restenosis more than does the normal homozygous or heterozygous
      genotype.

PMID- 11319194
TI  - Cytokines and cytokine receptors in advanced heart failure: an analysis of the
      cytokine database from the Vesnarinone trial (VEST).
AB  - BACKGROUND: Previous reports have shown that elevated circulating levels of
      cytokines and/or cytokine receptors predict adverse outcomes in patients with
      heart failure. However, these studies were limited by small numbers of patients
      and/or they were performed in a single center. In addition, these studies did not
      have sufficient size to address the influence of age, race, sex, and cause of
      heart failure on the circulating levels of these inflammatory mediators in
      patients with heart failure. METHODS AND RESULTS: We analyzed circulating levels
      of cytokines (tumor necrosis factor [TNF] and interleukin-6) and their cognate
      receptors in 1200 consecutive patients who were enrolled in a multicenter
      clinical trial of patients with advanced heart failure. This analysis constitutes
      the largest analysis of cytokines and cytokine receptors to date. Analysis of the
      patients receiving placebo showed that increasing circulating levels of TNF,
      interleukin-6, and the soluble TNF receptors were associated with increased
      mortality. In men, there was a linear increase in circulating levels of TNF with
      advancing age. Women < or = 50 years of age had relatively low levels of TNF, but
      TNF levels were disproportionately higher in women >50 years of age. No
      differences existed in cytokines and/or cytokine receptors in whites versus
      nonwhites, and circulating levels of cytokines and cytokine receptors were
      significantly greater in patients with ischemic heart disease. CONCLUSIONS:
      Cytokines and cytokine receptors are independent predictors of mortality in
      patients with advanced heart failure. Moreover, circulating levels of cytokines
      are modified by age, sex, and cause of heart failure.

PMID- 11319195
TI  - Electroanatomic mapping of entrained and exit zones in patients with repaired
      congenital heart disease and intra-atrial reentrant tachycardia.
AB  - BACKGROUND: Characterization of reentrant circuits and targeting ablation sites
      remains difficult for intra-atrial reentrant tachycardias (IART) in congenital
      heart disease (CHD). METHODS AND RESULTS: Electroanatomic mapping and entrainment
      pacing were performed before successful ablation of 18 IART circuits in 15
      patients with CHD. Principal features of IART circuits were atrial septal defect
      (4 patients), atriotomy (3 patients), other atrial scar (3 patients), crista
      terminalis (3 patients), and right atrioventricular valve (5 patients). A median
      of 176 sites (range, 96 to 317 sites) was mapped for activation and 13 sites
      (range, 9 to 28 sites) for entrainment response. Postpacing intervals within 20
      ms of tachycardia cycle length and stimulus-to-P-wave intervals of 0 to 90 ms
      (exit zones) were mapped to atrial surfaces generated by electroanatomic mapping.
      Criteria for entrainment were met over a median of 21 cm2 of atrial surface
      (range, 2 to 75 cm2), 19% (range, 1% to 81%) of total area tested. Using
      integrated data, relations between activation sequence and protected corridor of
      conduction could be inferred for 16 of 17 LARTs. Successful ablation was achieved
      at a site distant from the putative protected corridor in 9 of 18 (50%) circuits.
      CONCLUSIONS: The right atrium in CHD supports a variety of IART mechanisms.
      Fusion of activation and entrainment data provided insight into specific IART
      mechanisms relevant to ablation.

PMID- 11319196
TI  - Electrical storm presages nonsudden death: the antiarrhythmics versus implantable
      defibrillators (AVID) trial.
AB  - BACKGROUND: Electrical storm, multiple temporally related episodes of ventricular
      tachycardia (VT) or ventricular fibrillation (VF), is a frequent problem among
      recipients of implantable cardioverter defibrillators (ICDs). However,
      insufficient data exist regarding its prognostic significance. METHODS AND
      RESULTS: This analysis includes 457 patients who received an ICD in the
      Antiarrhythmics Versus Implantable Defibrillators (AVID) trial and who were
      followed for 31 +/- 13 months. Electrical storm was defined as > or = 3 separate
      episodes of VT/VF within 24 hours. Characteristics and survival of patients
      surviving electrical storm (n = 90), those with VT/VF unrelated to electrical
      storm (n = 184), and the remaining patients (n = 183) were compared. The 3 groups
      differed in terms of ejection fraction, index arrhythmia, revascularization
      status, and baseline medication use. Survival was evaluated using time-dependent
      Cox modeling. Electrical storm occurred 9.2 +/- 11.5 months after ICD
      implantation, and most episodes (86%) were due to VT. Electrical storm was a
      significant risk factor for subsequent death, independent of ejection fraction
      and other prognostic variables (relative risk [RR], 2.4; 95% confidence interval
      [CI], 1.3 to 4.2; P = 0.003), but VT/VF unrelated to electrical storm was not
      (RR, 1.0; 95% CI, 0.6 to 1.7; P = 0.9). The risk of death was greatest 3 months
      after electrical storm (RR, 5.4; 95% Cl, 2.4 to 12.3; P = 0.0001) and diminished
      beyond this time (RR, 1.9; 95% CI, 1.0 to 3.6; P=0.04). CONCLUSIONS: Electrical
      storm is an important, independent marker for subsequent death among ICD
      recipients, particularly in the first 3 months after its occurrence. However, the
      development of VT/VF unrelated to electrical storm does not seem to be associated
      with an increased risk of subsequent death.

PMID- 11319197
TI  - Baroreflex sensitivity and heart rate variability in the identification of
      patients at risk for life-threatening arrhythmias: implications for clinical
      trials.
AB  - BACKGROUND: The need for accurate risk stratification is heightened by the
      expanding indications for the implantable cardioverter defibrillator. The
      Multicenter Automatic Defibrillator Implantation Trial (MADIT) focused interest
      on patients with both depressed left ventricular ejection fraction (LVEF) and the
      presence of nonsustained ventricular tachycardia (NSVT). Meanwhile, the
      prospective study Autonomic Tone and Reflexes After Myocardial Infarctio (ATRAMI)
      demonstrated that markers of reduced vagal activity, such as depressed baroreflex
      sensitivity (BRS) an heart rate variability (HRV), are strong predictors of
      cardiac mortality after myocardial infarction. METHODS AND RESULTS: We analyzed
      1071 ATRAMI patients after myocardial infarction who had data on LVEF, 24-hour
      ECG recording, and BRS. During follow-up (21 +/- 8 months), 43 patients
      experienced cardiac death, 5 patients had episodes of sustained VT, and 30
      patients experienced sudden death and/or sustained VT. NSVT, depressed BRS, or
      HRV were all significantly and independently associated with increased mortality.
      The combination of all 3 risk factor increased the risk of death by 22x. Among
      patients with LVEF<35%, despite the absence of NSVT, depressed BRS predicted
      higher mortality (18% versus 4.6%, P = 0.01). This is a clinically important
      finding because this grou constitutes 25% of all patients with depressed LVEF.
      For both cardiac and arrhythmic mortality, the sensitivity of lo BRS was higher
      than that of NSVT and HRV CONCLUSIONS: BRS and HRV contribute importantly and
      additionally to risk stratification. Particularly when LVEF is depressed, the
      analysis of BRS identifies a large number of patients at high risk for cardiac
      and arrhythmic mortalit who might benefit from implantable cardioverter
      defibrillator therapy without disproportionately increasing the number of false
      positives.

PMID- 11319198
TI  - High-altitude pulmonary edema is initially caused by an increase in capillary
      pressure.
AB  - BACKGROUND: High-altitude pulmonary edema (HAPE) is characterized by severe
      pulmonary hypertension and bronchoalveolar lavage fluid changes indicative of
      inflammation. It is not known, however, whether the primary event is an increase
      in pressure or an increase in permeability of the pulmonary capillaries. METHODS
      AND RESULTS: We studied pulmonary hemodynamics, including capillary pressure
      determined by the occlusion method, and capillary permeability evaluated by the
      pulmonary transvascular escape of 67Ga-labeled transferrin, in 16 subjects with a
      previous HAPE and in 14 control subjects, first at low altitude (490 m) and then
      within the first 48 hours of ascent to a high-altitude laboratory (4559 m). The
      HAPE-susceptible subjects, compared with the control subjects, had an enhanced
      pulmonary vasoreactivity to inspiratory hypoxia at low altitude and higher mean
      pulmonary artery pressures (37 +/- 2 versus 26 +/- 1 mmHg, P<0.001) and pulmonary
      capillary pressures (19 +/- 1 versus 13 +/- 1 mmHg, P < 0.001) at high altitude.
      Nine of the susceptible subjects developed HAPE. All of them had a pulmonary
      capillary pressure >19 mm Hg (range 20 to 26 mmHg), whereas all 7 susceptible
      subjects without HAPE had a pulmonary capillary pressure < 19 mm Hg (range 14 to
      18 mm Hg). The pulmonary transcapillary escape of radiolabeled transferrin
      increased slightly from low to high altitude in the HAPE-susceptible subjects but
      remained within the limits of normal and did not differ significantly from the
      control subjects. CONCLUSIONS: HAPE is initially caused by an increase in
      pulmonary capillary pressure.

PMID- 11319199
TI  - Peripheral arterial responses to treadmill exercise among healthy subjects and
      atherosclerotic patients.
AB  - BACKGROUND-Peripheral cutaneous vascular beds, such as the fingertips, contain a
      high concentration of arteriovenous anastomoses, richly innervated by a
      adrenergic nerve fibers, to control heat regulation. Nevertheless, for a variety
      of technical reasons, finger blood flow responses to exercise have not been well
      studied in health and disease. Hence, we compared finger pulse-wave amplitude
      (PWA) responses to exercise among 50 normal volunteers and 57 patients with
      atherosclerotic coronary artery disease (CAD) using a robust, modified form of
      volume plethysmography. METHODS AND RESULTS: PWA was quantified for each minute
      of exercise as a ratio relative to baseline. Exercise PWA responses were compared
      with clinical, hemodynamic, ECG, and myocardial single photon emission computed
      tomography parameters. Among normal subjects, 38 (76%) manifested vasodilation
      throughout exercise and 12 (24%) manifested initial vasodilation followed by
      vasoconstriction at high heart rate thresholds. None manifested vasoconstriction
      throughout exercise. By contrast, 20 CAD patients (35%) manifested progressive
      vasoconstriction from the onset of exercise, and 10 others (18%) manifested
      vasoconstriction at low heart rate thresholds (P < 0.001 versus normals) after
      initial vasodilation with exercise. Patients exhibiting vasodilation versus
      vasoconstriction during exercise had similar clinical and exercise profiles,
      except for a greater use of ACE inhibitors and a greater level of achieved
      metabolic equivalents among the former (P<0.05 for both). CONCLUSIONS: Half of
      our CAD patients manifested diminution in PWA that was consistent with peripheral
      arterial vasoconstriction during the early phases of treadmill exercise. Such
      paradoxical vasoconstrictive responses were not observed in normal subjects and,
      therefore, they may represent generalized vascular pathology secondary to
      atherosclerosis.

PMID- 11319200
TI  - Selective augmentation of prostacyclin production by combined prostacyclin
      synthase and cyclooxygenase-1 gene transfer.
AB  - BACKGROUND: We tested the hypothesis that combined cyclooxygenase-1 (COX-1) and
      prostacyclin synthase (PGIS) gene transfer selectively augments prostacyclin
      production without a concurrent overproduction of other prostanoids. METHODS AND
      RESULTS: ECV304 cells were transfected with bicistronic pCOX-1/PGIS versus pCOX-1
      or pPGIS, and prostanoids were analyzed. Contrary to the high prostaglandin E2
      synthesis in pCOX-1 transfected cells, selective prostacyclin formation was noted
      with bicistronic plasmid transfection. Next, we determined the optimal ratio of
      Ad-COX-1 to Ad-PGIS by transfecting human umbilical vein endothelial cells with
      various titers of these 2 adenoviral constructs and determined the level of
      protein expression and prostanoid synthesis. Our results show that optimal ratios
      of adenoviral titers to achieve a large prostacyclin augmentation without
      overproduction of prostaglandin E2 or F2alpha were 50 to 100 plaque forming units
      (pfu) of Ad-COX-1 to 50 pfu of Ad-PGIS per cell. A higher Ad-PGIS to Ad-COX-1
      ratio caused a paradoxical decline in prostacyclin synthesis. CONCLUSIONS:
      Prostacyclin synthesis can be selectively augmented by cotransfecting endothelial
      cells with an optimal ratio of COX-1 to PGIS. Combined COX-1 and PGIS gene
      transfer has the potential for therapeutic augmentation of prostacyclin.

PMID- 11319201
TI  - New anti-monocyte chemoattractant protein-1 gene therapy attenuates
      atherosclerosis in apolipoprotein E-knockout mice.
AB  - BACKGROUND: Monocyte recruitment into the arterial wall and its activation may be
      the central event in atherogenesis. Monocyte chemoattractant protein-1 (MCP-1) is
      an important chemokine for monocyte recruitment, and its receptor (CCR2) may
      mediate such in vivo response. Although the importance of the MCP-1/CCR2 pathway
      in atherogenesis has been clarified, it remains unanswered whether postnatal
      blockade of the MCP-1 signals could be a unique site-specific gene therapy.
      METHODS AND RESULTS: We devised a new strategy for anti-MCP-1 gene therapy to
      treat atherosclerosis by transfecting an N-terminal deletion mutant of the human
      MCP-1 gene into a remote organ (skeletal muscle) in apolipoprotein E-knockout
      mice. This strategy effectively blocked MCP-1 activity and inhibited the
      formation of atherosclerotic lesions but had no effect on serum lipid
      concentrations. Furthermore, this strategy increased the lesional extracellular
      matrix content. CONCLUSIONS: We conclude that this anti-MCP-1 gene therapy may
      serve not only to reduce atherogenesis but also to stabilize vulnerable
      atheromatous plaques. This strategy may be a useful and feasible form of gene
      therapy against atherosclerosis in humans.

PMID- 11319202
TI  - Oxidized LDL inhibits vascular endothelial growth factor-induced endothelial cell
      migration by an inhibitory effect on the Akt/endothelial nitric oxide synthase
      pathway.
AB  - BACKGROUND: Oxidized LDL (oxLDL) inhibits endothelial cell (EC) migration.
      Stimulating ECs with vascular endothelial growth factor (VEGF) leads to the
      activation of Akt/protein kinase B, which in turn activates endothelial nitric
      oxide synthase (eNOS) by phosphorylation on serine 1177. VEGF-induced cell
      migration is dependent on the generation of nitric oxide (NO). Therefore, we
      investigated whether oxLDL affects EC migration by an inhibitory effect on the
      Akt/eNOS pathway. METHODS AND RESULTS: During an in vitro "scratched wound
      assay," oxLDL dose-dependently inhibited the VEGF-induced migration of human
      umbilical vein endothelial cells. Western blot analysis revealed that oxLDL dose-
      and time-dependently led to dephosphorylation and thus deactivation of Akt.
      Moreover, oxLDL inhibited the VEGF-induced generation of NO, as detected and
      quantified using a fluorescent NO indicator, 4,5-diaminofluorescein diacetate.
      Overexpression of a constitutively active Akt construct (Akt T308D/S473D) or a
      phosphomimetic eNOS construct (eNOS S1177D) almost completely reversed the
      inhibitory effect of oxLDL on VEGF-induced EC migration and NO generation.
      CONCLUSIONS: Our data indicate that oxLDL-induced dephosphorylation of Akt,
      followed by impaired eNOS activation, reduces the intracellular level of NO and
      thereby inhibits VEGF-induced EC migration.

PMID- 11319203
TI  - Long-term effects of intracoronary beta-radiation in balloon- and stent-injured
      porcine coronary arteries.
AB  - BACKGROUND: The data on the long-term safety and efficacy of intracoronary beta
      radiation in animal models are limited. METHODS AND RESULTS: A total of 30
      coronary arteries in 15 swine were subjected to balloon or stent injury followed
      by beta-radiation from a centered 32P source (2000 cGy to 1 mm beyond lumen
      surface) or a sham radiation procedure. The animals received aspirin for 6 months
      and ticlopidine for 30 days. Five of the 10 animals subjected to radiation died
      (at 5 days, 7 days, 3 months [n = 2], and 4 months) as a result of layered,
      occlusive thrombus at the intervention site (3 stent and 2 balloon injury sites).
      No deaths occurred in the control group. In the surviving animals, balloon
      injured and irradiated vessels showed a trend toward larger lumens than controls
      (2.15 +/- 0.17 versus 1.80 +/- 0.08 mm2, P=0.06) and larger external elastic
      lamina areas (3.32 +/- 0.21 versus 2.62 +/- 0.10 mm2, P=0.003). In the stent
      injured vessels from surviving animals, lumen, neointimal, and external elastic
      lamina areas were 3.58 +/- 0.33, 3.16 +/- 0.35, and 8.12 +/- 0.42 mm2 for
      irradiated vessel segments; these values were not different from those in
      controls (3.21 +/- 0.15, 2.84 +/- 0.27, and 7.76 +/- 0.28 mm2, respectively).
      Histologically, healing was complete in most survivors, although intramural
      fibrin and hemorrhage were occasionally seen. CONCLUSION: In the long-term (6
      month) porcine model of restenosis, the inhibition by intracoronary beta
      radiotherapy of the neointimal formation that is known to be present at 1 month
      is not sustained. This lack of effect on neointimal formation after balloon and
      stent arterial injury is accompanied by subacute and late thrombosis that leads
      to cardiac death on a background of continuous aspirin but relatively brief
      ticlopidine treatment.

PMID- 11319204
TI  - Potentiation of baroreceptor reflex response by heat shock protein 70 in nucleus
      tractus solitarii confers cardiovascular protection during heatstroke.
AB  - BACKGROUND: Whereas hypotension and bradycardia seen during the onset of
      heatstroke may be protected by prior induction of heat shock protein 70 (HSP70)
      in the brain, the underlying mechanism is not fully understood. We evaluated the
      hypothesis that HSP70 may confer cardiovascular protection during heatstroke by
      potentiating the baroreceptor reflex (BRR) control of peripheral hemodynamic
      performance. METHODS AND RESULTS: Adult male Sprague-Dawley rats subjected to a
      brief hyperthermic heat shock (HS; 42 degrees C for 15 minutes) induced
      discernible expression of HSP70 in the bilateral nucleus tractus solitarii (NTS),
      the terminal site in the brain stem for primary baroreceptor afferents. This
      HSP70 expression was detected at 8 hours, peaked at 24 hours, and returned to
      baseline by 48 hours after HS. Brief hyperthermia also significantly potentiated
      the BRR response in a temporal profile that correlated positively with changes in
      HSP70 expression at the NTS. Prior HS also appreciably alleviated hyperthermia,
      severe hypotension, and bradycardia manifested during the onset of heatstroke (45
      degrees C for 60 minutes) elicited 24 hours later. Microinjection bilaterally of
      anti-HSP70 antiserum (1:20) into the NTS or denervation of the sinoaortic
      baroreceptor afferents significantly reversed the enhancement of BRR response and
      cardiovascular protection during heatstroke induced by prior HS. CONCLUSIONS:
      These results suggest that HS-induced expression of HSP70 in the NTS may
      alleviate severe hypotension and bradycardia exhibited during the onset of
      heatstroke by potentiating both the sensitivity and capacity of BRR response.

PMID- 11319205
TI  - Nonpharmacological approaches to atrial fibrillation.

PMID- 11319206
TI  - Endovascular stent graft repair of an infrarenal abdominal aortic aneurysm with a
      horseshoe kidney.

PMID- 11319208
TI  - Electron Beam Computed Tomography for the Diagnosis and Prognosis of Coronary
      Artery Disease.

PMID- 11319207
TI  - Changing Electrocardiographic Patterns During Medical Treatment in a Patient With
      Anomalous Left Coronary Artery Originating From the Pulmonary Artery.

PMID- 11319209
TI  - Sudden Cardiac Death in Mitral Valve Prolapse.

PMID- 11319210
TI  - Cantrell's Syndrome: Left Ventricular Diverticulum in an Adult Patient.

PMID- 11319211
TI  - "Switched" Precordial Leads.

PMID- 11319212
TI  - Systemic Inflammation: The Central Factor in Pathogenesis of Unstable Angina.

PMID- 11319213
TI  - Cardiovascular News.

PMID- 11319214
TI  - Light- and guanosine 5'-3-O-(thio)triphosphate-sensitive localization of a G
      protein and its effector on detergent-resistant membrane rafts in rod
      photoreceptor outer segments.
AB  - Detergent-resistant membrane microdomains in the plasma membrane, known as lipid
      rafts, have been implicated in various cellular processes. We report here that a
      low-density Triton X-100-insoluble membrane (detergent-resistant membrane; DRM)
      fraction is present in bovine rod photoreceptor outer segments (ROS). In dark
      adapted ROS, transducin and most of cGMP-phosphodiesterase (PDE) were detergent
      soluble. When ROS membranes were exposed to light, however, a large portion of
      transducin localized in the DRM fraction. Furthermore, on addition of guanosine
      5'-3-O-(thio)triphosphate (GTPgammaS) to light-bleached ROS, transducin became
      detergent-soluble again. PDE was not recruited to the DRM fraction after light
      stimulus alone, but simultaneous stimulation by light and GTPgammaS induced a
      massive translocation of all PDE subunits to the DRM. A cholesterol-removing
      reagent, methyl-beta-cyclodextrin, selectively but partially solubilized PDE from
      the DRM, suggesting that cholesterol contributes, at least in part, to the
      association of PDE with the DRM. By contrast, transducin was not extracted by the
      depletion of cholesterol. These data suggest that transducin and PDE are likely
      to perform their functions in phototransduction by changing their localization
      between two distinct lipid phases, rafts and surrounding fluid membrane, on disc
      membranes in an activation-dependent manner.

PMID- 11319215
TI  - PAS domain receptor photoactive yellow protein is converted to a molten globule
      state upon activation.
AB  - Biological signaling generally involves the activation of a receptor protein by
      an external stimulus followed by protein-protein interactions between the
      activated receptor and its downstream signal transducer. The current paradigm for
      the relay of signals along a signal transduction chain is that it occurs by
      highly specific interactions between fully folded proteins. However, recent
      results indicate that many regulatory proteins are intrinsically unstructured,
      providing a serious challenge to this paradigm and to the nature of structure
      function relationships in signaling. Here we study the structural changes that
      occur upon activation of the blue light receptor photoactive yellow protein
      (PYP). Activation greatly reduces the tertiary structure of PYP but leaves the
      level secondary structure largely unperturbed. In addition, activated PYP exposes
      previously buried hydrophobic patches and allows significant solvent penetration
      into the core of the protein. These traits are the distinguishing hallmarks of
      molten globule states, which have been intensively studied for their role in
      protein folding. Our results show that receptor activation by light converts PYP
      to a molten globule and indicate stimulus-induced unfolding to a partially
      unstructured molten globule as a novel theme in signaling.

PMID- 11319216
TI  - Tyrosine kinase activation by the angiotensin II receptor in the absence of
      calcium signaling.
AB  - The angiotensin II type 1 (AT(1)) receptor signals via heterotrimeric G-proteins
      and intracellular tyrosine kinases. Here, we investigate a modified AT(1)
      receptor, termed M5, where the last five tyrosines (residues 292, 302, 312, 319,
      and 339) within the intracellular carboxyl tail have been mutated to
      phenylalanine. This receptor did not elevate cytosolic free calcium or inositol
      phosphate production in response to angiotensin II, suggesting an uncoupling of
      the receptor from G-protein activation. Despite this, the M5 receptor still
      activated tyrosine kinases, induced STAT1 tyrosine phosphorylation, and
      stimulated cell proliferation. We also studied another AT(1) mutant receptor,
      D74E, stably expressed in Chinese hamster ovarian cells and a fibroblast cell
      line from mice with a genetic inactivation of Galpha(q/11). Both cell lines have
      a deficit in calcium signaling and in G-protein activation, and yet in both cell
      lines, angiotensin II induced the time-dependent tyrosine phosphorylation of
      STAT1. These studies are the first to show the ability of a seven-transmembrane
      receptor to activate intracellular tyrosine kinase pathways in the absence of a G
      protein-coupled rise in intracellular calcium.

PMID- 11319217
TI  - A newly synthesized, ribosome-bound polypeptide chain adopts conformations
      dissimilar from early in vitro refolding intermediates.
AB  - Little is known about the conformations of newly synthesized polypeptide chains
      as they emerge from the large ribosomal subunit, or how these conformations
      compare with those populated immediately after dilution of polypeptide chains out
      of denaturant in vitro. Both in vivo and in vitro, partially folded intermediates
      of the tailspike protein from Salmonella typhimurium phage P22 can be trapped in
      the cold. A subset of monoclonal antibodies raised against tailspike recognize
      partially folded intermediates, whereas other antibodies recognize only later
      intermediates and/or the native state. We have used a pair of monoclonal
      antibodies to probe the conformational features of full-length, newly synthesized
      tailspike chains recovered on ribosomes from phage-infected cells. The antibody
      that recognizes early intermediates in vitro also recognizes the ribosome-bound
      intermediates. Surprisingly, the antibody that did not recognize early in vitro
      intermediates did recognize ribosome-bound tailspike chains translated in vivo.
      Thus, the newly synthesized, ribosome-bound tailspike chains display structured
      epitopes not detected upon dilution of tailspike chains from denaturant. As
      opposed to the random ensemble first populated when polypeptide chains are
      diluted out of denaturant, folding in vivo from the ribosome may begin with
      polypeptide conformations already directed toward the productive folding and
      assembly pathway.

PMID- 11319218
TI  - Membrane proximal ERK signaling is required for M-calpain activation downstream
      of epidermal growth factor receptor signaling.
AB  - Localization of signaling is critical in directing cellular outcomes, especially
      in pleiotropic signaling pathways. The extracellular signal-regulated kinase
      (ERK)/microtubule-associated protein kinase, which promotes cell migration,
      proliferation, and differentiation is found in the nucleus and throughout the
      cytoplasm. Recently, it has been shown that nuclear translocation of ERK is
      required for transcriptional changes and cell proliferation. However, the
      cellular consequences, of cytoplasmic signaling have not been defined. We
      explored whether cytoplasmic, specifically membrane-proximal, ERK signaling is
      involved in growth factor-induced cell motility. We previously have demonstrated
      that increased M-calpain activity downstream of epidermal growth factor receptor
      (EGFR)-mediated ERK activation is necessary for epidermal growth factor (EGF)
      induced motility. Calpain isoforms also have been found in nuclear, cytosolic,
      and plasma membrane-associated compartments in a variety of cell types. We now
      employ cell engineering approaches to control localization of the upstream EGFR
      and ERK activities to examine the spatial effect of upstream signal locale on
      downstream calpain activity. With differential ligand-induced internalization and
      trafficking-restricted receptor variants, we find that calpain activity is
      triggered only by plasma membrane-restricted activated EGFR, not by internalized
      (although still active) EGFR. Cells transfected with membrane-targeted ERK1 and
      ERK2, which sequester endogenous ERKs, exhibited normal EGF-induced calpain
      activity. Transfection of an inactive ERK phosphatase (MKP-3/Pyst1) that
      sequesters ERK in the cytoplasm prevented calpain activation as well as de
      adhesion. These data strongly suggest that EGF-induced calpain activity can be
      enhanced near sites of membrane-proximal EGFR-mediated ERK signaling, providing
      insights about how calpain activity might be regulated and targeted to enhance
      its effects on adhesion-related substrates.

PMID- 11319219
TI  - Investigating the structure of human RNase H1 by site-directed mutagenesis.
AB  - In this study we examine for the first time the roles of the various domains of
      human RNase H1 by site-directed mutagenesis. The carboxyl terminus of human RNase
      H1 is highly conserved with Escherichia coli RNase H1 and contains the amino acid
      residues of the putative catalytic site and basic substrate-binding domain of the
      E. coli RNase enzyme. The amino terminus of human RNase H1 contains a structure
      consistent with a double-strand RNA (dsRNA) binding motif that is separated from
      the conserved E. coli RNase H1 region by a 62-amino acid sequence. These studies
      showed that although the conserved amino acid residues of the putative catalytic
      site and basic substrate-binding domain are required for RNase H activity,
      deletion of either the catalytic site or the basic substrate-binding domain did
      not ablate binding to the heteroduplex substrate. Deletion of the region between
      the dsRNA-binding domain and the conserved E. coli RNase H1 domain resulted in a
      significant loss in the RNase H activity. Furthermore, the binding affinity of
      this deletion mutant for the heteroduplex substrate was approximately 2-fold
      tighter than the wild-type enzyme suggesting that this central 62-amino acid
      region does not contribute to the binding affinity of the enzyme for the
      substrate. The dsRNA-binding domain was not required for RNase H activity, as the
      dsRNA-deletion mutants exhibited catalytic rates approximately 2-fold faster than
      the rate observed for wild-type enzyme. Comparison of the dissociation constant
      of human RNase H1 and the dsRNA-deletion mutant for the heteroduplex substrate
      indicates that the deletion of this region resulted in a 5-fold loss in binding
      affinity. Finally, comparison of the cleavage patterns exhibited by the mutant
      proteins with the cleavage pattern for the wild-type enzyme indicates that the
      dsRNA-binding domain is responsible for the observed strong positional preference
      for cleavage exhibited by human RNase H1.

PMID- 11319220
TI  - The RING finger protein SNURF is a bifunctional protein possessing DNA binding
      activity.
AB  - The small nuclear C(3)HC(4) finger protein (SNURF), RNF4, acts as transcriptional
      coactivator for both steroid-dependent and -independent promoters such as those
      driven by androgen response elements and GC boxes, respectively. However, SNURF
      does not possess intrinsic transcription activation function, and the precise
      molecular mechanism of its action is unknown. We have studied herein the
      interaction of SNURF with DNA in vitro. SNURF binds to linear double-stranded DNA
      with no apparent sequence specificity in a cooperative fashion that is highly
      dependent on the length of the DNA fragment used. SNURF interacts efficiently
      with both supercoiled circular and four-way junction DNA, and importantly, it
      also recognizes nucleosomes. An intact RING structure of SNURF is not mandatory
      for DNA binding, whereas mutations of specific positively charged residues in the
      N terminus (amino acids 8-11) abolish DNA binding. Interestingly, the ability of
      SNURF to interact with DNA is associated with its capability to enhance
      transcription from promoters containing GC box elements. Because SNURF can
      interact with both DNA and protein (transcription) factors, it may promote
      assembly of nucleoprotein structures.

PMID- 11319221
TI  - Synergistic activity of STAT3 and c-Jun at a specific array of DNA elements in
      the alpha 2-macroglobulin promoter.
AB  - The transcriptional activity of natural promoters is sensitive to the precise
      spatial arrangement of DNA elements and their incorporation into higher order DNA
      protein complexes. STAT3 and c-Jun form a specific ternary complex in vitro with
      a synthetic DNA element containing AP1 and SIE sites. These associations are
      critical for synergistic activation of transcription from a synthetic promoter by
      STAT3 and c-Jun. Expression of the acute phase protein alpha(2)-macroglobulin is
      induced in vivo by interleukin-6 (IL-6)-related cytokines; we demonstrate that
      coordinate interactions among STAT3, c-Jun, and a specific array of DNA elements
      contribute to activation of the alpha(2)-macroglobulin promoter in response to IL
      6 family members. At least five promoter elements are involved in activation: two
      AP1 sites at -113 to -107 and -152 to -140, an acute phase response element (APRE
      (SIE)) at -171 to -163, and two AT-rich regions at -143 to -138 and -128 to -123.
      Synergism between STAT3 or STAT3-C and c-Jun is impaired by mutation of the APRE
      (SIE) or either AP1 site, as well as by mutations that alter the AT-rich regions
      or their phasing. Mutations of STAT3 previously shown to disrupt physical and
      functional interactions with c-Jun do not impair synergy between STAT3-C and c
      Jun at the alpha(2)-macroglobulin promoter in HepG2 cells, suggesting that STAT3
      C and STAT3 differ with respect to their precise contacts with c-Jun.

PMID- 11319223
TI  - Point mutations identified in Lec8 Chinese hamster ovary glycosylation mutants
      that inactivate both the UDP-galactose and CMP-sialic acid transporters.
AB  - Nucleotide-sugar transporters (NSTs) are critical components of glycosylation
      pathways in eukaryotes. The identification of structural elements that are
      involved in NST functions provides an important task. Chinese hamster ovary
      glycosylation mutants defective in nucleotide-sugar transport provide access to
      inactive transporters that can define such structure/function relationships. In
      this study, we have cloned the hamster UDP-galactose transporter (UGT) and
      identified defects in UGT gene transcripts from nine independent Chinese hamster
      ovary mutants that belong to the Lec8 complementation group. Reverse
      transcription polymerase chain reaction with primers that span the UGT open
      reading frame showed that three Lec8 mutants express a full-length open reading
      frame, while six Lec8 mutants predominantly express truncated UGT gene
      transcripts. Sequencing identified different single or triplet nucleotide changes
      in full-length UGT transcripts from three of the mutants. These mutations
      translate into three different amino acid changes at positions that are highly
      conserved in all the known mammalian NSTs. Transfection of a cDNA encoding either
      of the mutations Delta serine 213 or G281D failed to correct the UDP-galactose
      transport defect in Lec8 transfectants. Most importantly, introducing these same
      mutations into the homologous region of the murine CMP-sialic acid transporter
      caused inactivation of this transporter. Thus, identifying point mutations that
      inactivate UGT in Lec8 mutants resulted in the discovery of amino acids that are
      critical to the activity of both UGT and CST, the two most divergent mammalian
      NSTs.

PMID- 11319222
TI  - Expression and characterization of recombinant rat Acyl-CoA synthetases 1, 4, and
      5. Selective inhibition by triacsin C and thiazolidinediones.
AB  - Inhibition by triacsins and troglitazone of long chain fatty acid incorporation
      into cellular lipids suggests the existence of inhibitor-sensitive and -resistant
      acyl-CoA synthetases (ACS, EC ) that are linked to specific metabolic pathways.
      In order to test this hypothesis, we cloned and purified rat ACS1, ACS4, and
      ACS5, the isoforms present in liver and fat cells, expressed the isoforms as ACS
      Flag fusion proteins in Escherichia coli, and purified them by Flag affinity
      chromatography. The Flag epitope at the C terminus did not alter the kinetic
      properties of the enzyme. Purified ACS1-, 4-, and 5-Flag isoforms differed in
      their apparent K(m) values for ATP, thermolability, pH optima, requirement for
      Triton X-100, and sensitivity to N-ethylmaleimide and phenylglyoxal. The ACS
      inhibitor triacsin C strongly inhibited ACS1 and ACS4, but not ACS5. The
      thiazolidinedione (TZD) insulin-sensitizing drugs and peroxisome proliferator
      activated receptor gamma (PPARgamma) ligands, troglitazone, rosiglitazone, and
      pioglitazone, strongly and specifically inhibited only ACS4, with an IC(50) of
      less than 1.5 microm. Troglitazone exhibited a mixed type inhibition of ACS4.
      alpha-Tocopherol, whose ring structure forms the non-TZD portion of troglitazone,
      did not inhibit ACS4, indicating that the thiazolidine-2,4-dione moiety is the
      critical component for inhibition. A non-TZD PPARgamma ligand, GW1929, which is 7
      fold more potent than rosiglitazone, inhibited ACS1 and ACS4 poorly with an
      IC(50) of greater than 50 microm, more than 100-fold higher than was required for
      rosiglitazone, thereby demonstrating the specificity of TZD inhibition. Further,
      the PPARalpha ligands, clofibrate and GW4647, and various xenobiotic carboxylic
      acids known to be incorporated into complex lipids had no effect on ACS1, -4, or 
      5. These results, together with previous data showing that triacsin C and
      troglitazone strongly inhibit triacylglycerol synthesis compared with other
      metabolic pathways, suggest that ACS1 and ACS4 catalyze the synthesis of acyl
      CoAs used for triacylglycerol synthesis and that lack of inhibition of a
      metabolic pathway by triacsin C does not prove lack of acyl-CoA involvement. The
      results further suggest the possibility that the insulin-sensitizing effects of
      the thiazolidinedione drugs might be achieved, in part, through direct
      interaction with ACS4 in a PPARgamma-independent manner.

PMID- 11319224
TI  - The N-terminal nuclear export sequence of IkappaBalpha is required for RanGTP
      dependent binding to CRM1.
AB  - Nuclear export of IkappaBalpha is mediated by the CRM1 nuclear export receptor.
      However, the identity of the nuclear export sequences NES(s) in IkappaBalpha that
      are responsible for binding of IkappaBalpha to CRM1 is controversial. Both a N
      terminal NES-like region (amino acids 45-54) and a C-terminal NES-like region
      (amino acids 265-280) have, in a number of reports from different laboratories,
      been implicated in CRM1-dependent nuclear export of IkappaBalpha. We now
      demonstrate that the N-terminal NES-like region, but not the C-terminal NES-like
      region, is required for RanGTP-dependent binding of IkappaBalpha to CRM1.
      IkappaBalpha is a relatively weak substrate for CRM1, with an affinity for CRM1
      that is 100-fold less than the minute virus of mice NS2 protein, a high affinity
      cargo protein for CRM1. We also demonstrate that IkappaBalpha functions as a
      physical adaptor between CRM1 and NFkappaB/Rel proteins. Both free IkappaBalpha
      and Rel-associated IkappaBalpha have comparable affinities for CRM1, suggesting
      that CRM1 does not discriminate between free IkappaBalpha and Rel-associated
      IkappaBalpha. Nuclear export of c-Rel by IkappaBalpha requires the N-terminal NES
      like sequence of IkappaBalpha but is not affected by alanine substitutions within
      the C-terminal NES-like sequence of IkappaBalpha. In contrast, nuclear export of
      the v-Rel oncoprotein by IkappaBalpha is disrupted by alanine substitutions
      within either the N-terminal or the C-terminal NES-like sequences. However,
      alanine substitutions within the C-terminal NES-like sequence significantly
      reduce the affinity of IkappaBalpha for v-Rel, suggesting that loss of export
      function for this mutant is secondary to reduced association between IkappaBalpha
      and v-Rel. Taken together, our results demonstrate that the N-terminal NES-like
      sequence in IkappaBalpha is required for RanGTP-dependent binding of both free
      IkappaBalpha and NFkappaB/Rel-associated IkappaBalpha proteins to CRM1.

PMID- 11319225
TI  - Invariant Asp-1122 and Asp-1124 are essential residues for polymerization
      catalysis of family D DNA polymerase from Pyrococcus horikoshii.
AB  - Family D DNA polymerase has recently been found in the Euryarchaeota subdomain of
      Archaea. Its genes are adjacent to several other genes related to DNA
      replication, repair, and recombination in the genome, suggesting that this enzyme
      may be the major DNA replicase in Euryarchaeota. Although it possesses strong
      polymerization and proofreading activities, the motifs common to other DNA
      polymerase families are absent in its sequences. Here we report the mapping of
      the catalytic residues in a family D DNA polymerase from Pyrococcus horikoshii.
      Site-directed alanine mutants for 28 conserved aspartic acid or glutamic acid
      residues were screened for polymerization and 3'-5' exonuclease activities. We
      identified the invariant aspartates Asp-1122 and Asp-1124 within the most
      conserved motif as the catalytic residues involved in DNA polymerization. Alanine
      mutation at either site caused a loss of polymerization activity, whereas the
      conserved mutants, D1122E, D1124N, and D1124E, had slightly reduced
      polymerization activity. We also found that the 3'-5' exonuclease activity
      remains in D1122A and D1124A, indicating that the catalytic residues of DNA
      polymerization are different from those of the 3'-5' exonuclease activity.
      Furthermore we determined the molecular mass of the recombinant enzyme by gel
      filtration and proposed a heterotetrameric structure for this enzyme.

PMID- 11319226
TI  - Ca2+ and BMP-6 signaling regulate E2F during epidermal keratinocyte
      differentiation.
AB  - The epidermis consists of a squamous epithelium continuously replenished by
      committed stem cells, which can either self-renew or differentiate. We
      demonstrated previously that E2F genes are differentially expressed in developing
      epidermis (Dagnino, L., Fry, C. J., Bartley, S. M., Farnham, P., Gallie, B. L.,
      and Phillips, R. A. (1997) Cell Growth Differ. 8, 553-563). Thus, we hypothesized
      that various E2F proteins likely play distinct growth regulatory roles in the
      undifferentiated stem cells and in terminally differentiated keratinocytes. To
      further understand the function of E2F genes in epidermal morphogenesis, we have
      examined the expression, regulation, and protein-protein interactions of E2F
      factors in undifferentiated cultured murine primary keratinocytes or in cells
      induced to differentiate with Ca(2+) or BMP-6 (bone morphogenetic protein 6). We
      find similar patterns of E2F regulation with both differentiating agents and
      demonstrate a switch in expression from E2F-1, -2, and -3 in undifferentiated,
      proliferating cells to E2F-5 in terminally differentiated keratinocytes.
      Inhibition of keratinocyte proliferation by transforming growth factor-beta1 did
      not enhance E2F-5 protein levels, suggesting that this response is specific to
      differentiation rather than reversible cell cycle withdrawal. E2F-5 up-regulation
      is also accompanied by formation of heteromeric nuclear complexes containing
      E2F5, p130, and histone deacetylase (HDAC) 1. Overexpression of E2F5 specifically
      inhibited DNA synthesis in undifferentiated keratinocytes in an HDAC-dependent
      manner, suggesting that E2F-5.p130.HDAC1 complexes are likely involved in the
      permanent withdrawal from the cell cycle of keratinocytes responding to
      differentiation stimuli.

PMID- 11319227
TI  - Crystal structure of the eosinophil major basic protein at 1.8 A. An atypical
      lectin with a paradigm shift in specificity.
AB  - The eosinophil major basic protein (EMBP) is the predominant constituent of the
      crystalline core of the eosinophil primary granule. EMBP is directly implicated
      in epithelial cell damage, exfoliation, and bronchospasm in allergic diseases
      such as asthma. Here we report the crystal structure of EMBP at 1.8 A resolution,
      and show that it is similar to that of members of the C-type lectin superfamily
      with which it shares minimal amino acid sequence identity (approximately 15-
      28%). However, this protein lacks a Ca(2+)/carbohydrate-binding site. Our
      analysis suggests that EMBP specifically binds heparin. Based on our results, we
      propose a possible new function for this protein, which is likely to have
      implications for EMBP function.

PMID- 11319228
TI  - Differential incorporation and removal of antiviral deoxynucleotides by human DNA
      polymerase gamma.
AB  - Mitochondrial toxicity can result from antiviral nucleotide analog therapy used
      to control human immunodeficiency virus type 1 infection. We evaluated the
      ability of such analogs to inhibit DNA synthesis by the human mitochondrial DNA
      polymerase (pol gamma) by comparing the insertion and exonucleolytic removal of
      six antiviral nucleotide analogs. Apparent steady-state K(m) and k(cat) values
      for insertion of 2',3'-dideoxy-TTP (ddTTP), 3'-azido-TTP (AZT-TP), 2',3'-dideoxy
      CTP (ddCTP), 2',3'-didehydro-TTP (D4T-TP), (-)-2',3'-dideoxy-3'-thiacytidine (3TC
      TP), and carbocyclic 2',3'-didehydro-ddGTP (CBV-TP) indicated incorporation of
      all six analogs, albeit with varying efficiencies. Dideoxynucleotides and D4T-TP
      were utilized by pol gamma in vitro as efficiently as natural deoxynucleotides,
      whereas AZT-TP, 3TC-TP, and CBV-TP were only moderate inhibitors of DNA chain
      elongation. Inefficient excision of dideoxynucleotides, D4T, AZT, and CBV from
      DNA predicts persistence in vivo following successful incorporation. In contrast,
      removal of 3'-terminal 3TC residues was 50% as efficient as natural 3' termini.
      Finally, we observed inhibition of exonuclease activity by concentrations of AZT
      monophosphate known to occur in cells. Thus, although their greatest inhibitory
      effects are through incorporation and chain termination, persistence of these
      analogs in DNA and inhibition of exonucleolytic proofreading may also contribute
      to mitochondrial toxicity.

PMID- 11319229
TI  - Regulation of plasmin-dependent fibrin clot lysis by annexin II heterotetramer.
AB  - In a previous report we showed that plasmin-dependent lysis of a fibrin polymer,
      produced from purified components, was totally blocked if annexin II
      heterotetramer (AIIt) was present during fibrin polymer formation. Here, we show
      that AIIt inhibits fibrin clot lysis by stimulation of plasmin autodegradation,
      which results in a loss of plasmin activity. Furthermore, the C-terminal lysine
      residues of its p11 subunit play an essential role in the inhibition of fibrin
      clot lysis by AIIt. We also found that AIIt binds to fibrin with a K(d) of 436 nm
      and a stoichiometry of about 0.28 mol of AIIt/mol of fibrin monomer. The binding
      of AIIt to fibrin was not dependent on the C-terminal lysines of the p11 subunit.
      Furthermore, in the presence of plasminogen, the binding of AIIt to fibrin was
      increased to about 1.3 mol of AIIt/mol of fibrin monomer, suggesting that AIIt
      and plasminogen do not compete for identical sites on fibrin. Immunohistochemical
      identification of p36 and p11 subunits of AIIt in a pathological clot provides
      important evidence for its role as a physiological fibrinolytic regulator. These
      results suggest that AIIt may play a key role in the regulation of plasmin
      activity on the fibrin clot surface.

PMID- 11319230
TI  - Design, engineering, and production of human recombinant t cell receptor ligands
      derived from human leukocyte antigen DR2.
AB  - Major histocompatibility complex (MHC) class II molecules are membrane-anchored
      heterodimers on the surface of antigen-presenting cells that bind the T cell
      receptor, initiating a cascade of interactions that results in antigen-specific
      activation of clonal populations of T cells. Susceptibility to multiple sclerosis
      is associated with certain MHC class II haplotypes, including human leukocyte
      antigen (HLA) DR2. Two DRB chains, DRB5*0101 and DRB1*1501, are co-expressed in
      the HLA-DR2 haplotype, resulting in the formation of two functional cell surface
      heterodimers, HLA-DR2a (DRA*0101, DRB5*0101) and HLA-DR2b (DRA*0101, DRB1*1501).
      Both isotypes can present an immunodominant peptide of myelin basic protein (MBP
      (84-102)) to MBP-specific T cells from multiple sclerosis patients. We have
      previously demonstrated that the peptide binding/T cell recognition domains of
      rat MHC class II (alpha1 and beta1 domains) could be expressed as a single exon
      for structural and functional characterization; Burrows, G. G., Chang, J. W.,
      Bachinger, H.-P., Bourdette, D. N., Wegmann, K. W., Offner, H., and Vandenbark A.
      A. (1999) Protein Eng. 12, 771-778; Burrows, G. G., Adlard, K. L., Bebo, B. F.,
      Jr., Chang, J. W., Tenditnyy, K., Vandenbark, A. A., and Offner, H. (2000) J.
      Immunol. 164, 6366-6371). Single-chain human recombinant T cell receptor ligands
      (RTLs) of approximately 200 amino acid residues derived from HLA-DR2b were
      designed using the same principles and have been produced in Escherichia coli
      with and without amino-terminal extensions containing antigenic peptides.
      Structural characterization using circular dichroism predicted that these
      molecules retained the antiparallel beta-sheet platform and antiparallel alpha
      helices observed in the native HLA-DR2 heterodimer. The proteins exhibited a
      cooperative two-state thermal unfolding transition, and DR2-derived RTLs with a
      covalently linked MBP peptide (MBP-(85-99)) showed increased stability to thermal
      unfolding relative to the empty DR2-derived RTLs. These novel molecules represent
      a new class of small soluble ligands for modulating the behavior of T cells and
      provide a platform technology for developing potent and selective human
      diagnostic and therapeutic agents for treatment of autoimmune disease.

PMID- 11319231
TI  - Targeting and processing of nuclear-encoded apicoplast proteins in plastid
      segregation mutants of Toxoplasma gondii.
AB  - The apicoplast is a distinctive organelle associated with apicomplexan parasites,
      including Plasmodium sp. (which cause malaria) and Toxoplasma gondii (the
      causative agent of toxoplasmosis). This unusual structure (acquired by the
      engulfment of an ancestral alga and retention of the algal plastid) is essential
      for long-term parasite survival. Similar to other endosymbiotic organelles
      (mitochondria, chloroplasts), the apicoplast contains proteins that are encoded
      in the nucleus and post-translationally imported. Translocation across the four
      membranes surrounding the apicoplast is mediated by an N-terminal bipartite
      targeting sequence. Previous studies have described a recombinant "poison" that
      blocks plastid segregation during mitosis, producing parasites that lack an
      apicoplast and siblings containing a gigantic, nonsegregating plastid. To learn
      more about this remarkable phenomenon, we examined the localization and
      processing of the protein produced by this construct. Taking advantage of the
      ability to isolate apicoplast segregation mutants, we also demonstrated that
      processing of the transit peptide of nuclear-encoded apicoplast proteins requires
      plastid-associated activity.

PMID- 11319232
TI  - Acyl-CoA synthetase isoforms 1, 4, and 5 are present in different subcellular
      membranes in rat liver and can be inhibited independently.
AB  - Inhibition studies have suggested that acyl-CoA synthetase (ACS, EC ) isoforms
      might regulate the use of acyl-CoAs by different metabolic pathways. In order to
      determine whether the subcellular locations differed for each of the three ACSs
      present in liver and whether these isoforms were regulated independently, non
      cross-reacting peptide antibodies were raised against ACS1, ACS4, and ACS5. ACS1
      was identified in endoplasmic reticulum, mitochondria-associated membrane (MAM),
      and cytosol, but not in mitochondria. ACS4 was present primarily in MAM, and the
      76-kDa ACS5 protein was located in mitochondrial membrane. Consistent with these
      locations, N-ethylmaleimide, an inhibitor of ACS4, inhibited ACS activity 47% in
      MAM and 28% in endoplasmic reticulum. Troglitazone, a second ACS4 inhibitor,
      inhibited ACS activity <10% in microsomes and mitochondria and 45% in MAM.
      Triacsin C, a competitive inhibitor of both ACS1 and ACS4, inhibited ACS activity
      similarly in endoplasmic reticulum, MAM, and mitochondria, suggesting that a
      hitherto unidentified triacsin-sensitive ACS is present in mitochondria. ACS1,
      ACS4, and ACS5 were regulated independently by fasting and re-feeding. Fasting
      rats for 48 h resulted in a decrease in ACS4 protein, and an increase in ACS5. Re
      feeding normal chow or a high sucrose diet for 24 h after a 48-h fast increased
      both ACS1 and ACS4 protein expression 1.5-2.0-fold, consistent with inhibition
      studies. These results suggest that ACS1 and ACS4 may be linked to
      triacylglycerol synthesis. Taken together, the data suggest that acyl-CoAs may be
      functionally channeled to specific metabolic pathways through different ACS
      isoforms in unique subcellular locations.

PMID- 11319233
TI  - Importance of transmembrane segment M3 of the sarcoplasmic reticulum Ca2+-ATPase
      for control of the gateway to the Ca2+ sites.
AB  - The specific functional roles of various parts of the third transmembrane segment
      (M3) of the sarcoplasmic reticulum Ca(2+)-ATPase were examined by functionally
      characterizing a series of mutants with multiple or single substitutions of M3
      residues. Steady-state and transient kinetic measurements, assisted by computer
      simulation of the time and Ca(2+) dependences of the phosphorylation level, were
      used to study the partial reaction steps of the enzyme cycle, including the
      binding and dissociation of Ca(2+) at the high affinity cytoplasmically facing
      sites. The mutation Lys-Leu-Asp-Glu(255) --> Glu-Ile-Glu-His resulted in a
      conspicuous increase in the rate of Ca(2+) dissociation as well as a displacement
      of the major conformational equilibria of the phosphoenzyme and dephosphoenzyme
      forms. The point mutant Phe(256) --> Ala also showed an increased rate of Ca(2+)
      dissociation, whereas a conspicuous decrease both in the rate of Ca(2+)
      dissociation and in the rate of Ca(2+) binding was found for the mutant Gly-Glu
      Gln-Leu(260) --> Ile-His-Leu-Ile. These findings suggest that the NH(2)-terminal
      half of M3 is involved in control of the gateway to the Ca(2+) sites. The main
      effect of two mutations to the COOH-terminal half of M3, Ser-Lys-Val-Ile-Ser(265)
      --> Thr-Gly-Val-Ala-Val and Leu-Ile-Cys-Val-Ala-Val-Trp-Leu-Ile(274) --> Phe-Leu
      Gly-Val-Ser-Phe-Phe-Ile-Leu, was a block of the dephosphorylation.

PMID- 11319235
TI  - A role of the C-terminal part of p44 in the promoter escape activity of
      transcription factor IIH.
AB  - The p44 subunit plays a crucial role in the overall activity of the
      transcription/DNA repair factor TFIIH: on the one hand its N-terminal domain
      interacts with and regulates the XPD helicase (, ); on the other hand, as shown
      in the present study, it participates with the promoter escape reaction.
      Mutagenesis along with recombinant technology using the baculovirus/insect cells
      expression system allowed us to define the function of the two structural motifs
      of the C-terminal moiety of p44: mutations within the C4 zinc finger motif
      (residues 291-308) prevent incorporation of the p62 subunit within the core
      TFIIH. Double mutations in the RING finger motif (residues 345-385) allow the
      synthesis of the first phosphodiester bond by RNA polymerase II, but prevent its
      escape from the promoter. This highlights the role of transcription factor IIH in
      the various steps of the transcription initiation process.

PMID- 11319236
TI  - Iron-sulfur cluster assembly: characterization of IscA and evidence for a
      specific and functional complex with ferredoxin.
AB  - The synthesis of iron-sulfur clusters in Escherichia coli is believed to require
      a complex protein machinery encoded by the isc (iron-sulfur cluster) operon. The
      product of one member of this operon, IscA, has been overexpressed, purified, and
      characterized. It can assemble an air-sensitive [2Fe-2S] cluster as shown by UV
      visible and resonance Raman spectroscopy. The metal form but not the apoform of
      IscA binds ferredoxin, another member of the isc operon, selectively, allowing
      transfer of iron and sulfide from IscA to ferredoxin and formation of the [2Fe
      2S] holoferredoxin. These results thus suggest that IscA is involved in
      ferredoxin cluster assembly and activation. This is an important function because
      a functional ferredoxin is required for maturation of other cellular Fe-S
      proteins.

PMID- 11319234
TI  - A mammalian homolog of yeast MOB1 is both a member and a putative substrate of
      striatin family-protein phosphatase 2A complexes.
AB  - Striatin and S/G(2) nuclear autoantigen (SG2NA) are related proteins that contain
      membrane binding domains and associate with protein phosphatase 2A (PP2A) and
      many additional proteins that may be PP2A regulatory targets. Here we identify a
      major member of these complexes as class II mMOB1, a mammalian homolog of the
      yeast protein MOB1, and show that its phosphorylation appears to be regulated by
      PP2A. Yeast MOB1 is critical for cytoskeletal reorganization during cytokinesis
      and exit from mitosis. We show that mMOB1 associated with PP2A is not detectably
      phosphorylated in asynchronous murine fibroblasts. However, treatment with the
      PP2A inhibitor okadaic acid induces phosphorylation of PP2A-associated mMOB1 on
      serine. Moreover, specific inhibition of PP2A also results in
      hyperphosphorylation of striatin, SG2NA, and three unidentified proteins,
      suggesting that these proteins may also be regulated by PP2A. Indirect
      immunofluorescence produced highly similar staining patterns for striatin, SG2NA,
      and mMOB1, with the highest concentrations for each protein adjacent to the
      nuclear membrane. We also present evidence that these complexes may interact with
      each other. These data are consistent with a model in which PP2A may regulate
      mMOB1, striatin, and SG2NA to modulate changes in the cytoskeleton or
      interactions between the cytoskeleton and membrane structures.

PMID- 11319237
TI  - Characterization of the laminin binding domains of the Lutheran blood group
      glycoprotein.
AB  - Lutheran (Lu) blood group antigens and the basal cell adhesion molecule antigen
      reside on two glycoproteins that belong to the Ig superfamily (IgSF) and carry
      five Ig-like extracellular domains. These glycoproteins act as widely expressed
      adhesion molecules and represent the unique receptors for laminin-10/11 in
      erythroid cells. Here, we report the mapping of IgSF domains responsible for
      binding to laminin. In plasmonic resonance surface experiments, only recombinant
      Lu proteins containing the N-terminal IgSF domains 1-3 were able to bind laminin
      10/11 and to inhibit binding of laminin to Lu-expressing K562 cells. Mutant
      recombinant proteins containing only IgSF domain 1, domains 1 + 2, domains 1 + 3,
      domains 2 + 3, domain 3, domain 4, domain 5, and domains 4 + 5 failed to bind
      laminin as well as a construct containing all of the extracellular domains except
      domain 3. Altogether, these results indicate that IgSF domains 1-3 are involved
      in laminin binding and that a specific spatial arrangement of these three first
      domains is most probably necessary for interaction. Neither the RGD nor the N
      glycosylation motifs present in IgSF domain 3 were involved in laminin binding.

PMID- 11319238
TI  - Polyglutamine-expanded huntingtin promotes sensitization of N-methyl-D-aspartate
      receptors via post-synaptic density 95.
AB  - Increased glutamate-mediated excitotoxicity seems to play an important role in
      the pathogenesis of Huntington's disease (Tabrizi, S. J., Cleeter, M. W., Xuereb,
      J., Taaman, J. W., Cooper, J. M., and Schapira, A. H. (1999) Ann. Neurol. 45, 25
      32). However, how polyglutamine expansion in huntingtin promotes glutamate
      mediated excitotoxicity remains a mystery. In this study we provide evidence that
      (i) normal huntingtin is associated with N-methyl-d-aspartate (NMDA) and kainate
      receptors via postsynaptic density 95 (PSD-95), (ii) the SH3 domain of PSD-95
      mediates its binding to huntingtin, and (iii) polyglutamine expansion interferes
      with the ability of huntingtin to interact with PSD-95. The expression of
      polyglutamine-expanded huntingtin causes sensitization of NMDA receptors and
      promotes neuronal apoptosis induced by glutamate. The addition of the NMDA
      receptor antagonist significantly attenuates neuronal toxicity induced by
      glutamate and polyglutamine-expanded huntingtin. The overexpression of normal
      huntingtin significantly inhibits neuronal toxicity mediated by NMDA or kainate
      receptors. Our results demonstrate that polyglutamine expansion impairs the
      ability of huntingtin to bind PSD-95 and inhibits glutamate-mediated
      excitotoxicity. These changes may be essential for the pathogenesis of
      Huntington's disease.

PMID- 11319239
TI  - Selective interaction of triazole derivatives with DWF4, a cytochrome P450
      monooxygenase of the brassinosteroid biosynthetic pathway, correlates with
      brassinosteroid deficiency in planta.
AB  - Brassinazole, a synthetic chemical developed in our laboratory, is a triazole
      type brassinosteroid biosynthesis inhibitor that induces dwarfism in various
      plant species. The target sites of brassinazole were investigated by chemical
      analyses of endogenous brassinosteroids (BRs) in brassinazole-treated
      Catharanthus roseus cells. The levels of castasterone and brassinolide in
      brassinazole-treated plant cells were less than 6% of the levels in untreated
      cells. In contrast, campestanol and 6-oxocampestanol levels were increased, and
      levels of BR intermediates with hydroxy groups on the side chains were reduced,
      suggesting that brassinazole treatment reduced BR levels by inhibiting the
      hydroxylation of the C-22 position. DWF4, which is an Arabidopsis thaliana
      cytochrome P450 isolated as a putative steroid 22-hydroxylase, was expressed in
      Escherichia coli, and the binding affinity of brassinazole and its derivatives to
      the recombinant DWF4 were analyzed. Among several triazole derivatives,
      brassinazole had both the highest binding affinity to DWF4 and the highest growth
      inhibitory activity. The binding affinity and the activity for inhibiting
      hypocotyl growth were well correlated among the derivatives. In brassinazole
      treated A. thaliana, the CPD gene involved in BR biosynthesis was induced within
      3 h, most likely because of feedback activation caused by the reduced levels of
      active BRs. These results indicate that brassinazole inhibits the hydroxylation
      of the C-22 position of the side chain in BRs by direct binding to DWF4 and that
      DWF4 catalyzes this hydroxylation reaction.

PMID- 11319240
TI  - Attenuated zymosan-induced peritoneal vascular permeability and IgE-dependent
      passive cutaneous anaphylaxis in mice lacking leukotriene C4 synthase.
AB  - Leukotriene C(4) synthase (LTC(4)S), the terminal 5-lipoxygenase pathway enzyme
      that is responsible for the biosynthesis of cysteinyl leukotrienes, has been
      deleted by targeted gene disruption to define its tissue distribution and
      integrated pathway function in vitro and in vivo. The LTC(4)S (-/-) mice
      developed normally and were fertile. LTC(4)S activity, assessed by conjugation of
      leukotriene (LT) A(4) methyl ester with glutathione, was absent from tongue,
      spleen, and brain and > or = 90% reduced in lung, stomach, and colon of the
      LTC(4)S (-/-) mice. Bone marrow-derived mast cells (BMMC) from the LTC(4)S (-/-)
      mice provided no LTC(4) in response to IgE-dependent activation. Exocytosis and
      the generation of prostaglandin D(2), LTB(4), and 5-hydroxyeicosatetraenoic acid
      by BMMC from LTC(4)S (-/-) mice and LTC(4)S (+/+) mice were similar, whereas the
      degraded product of LTA(4), 6-trans-LTB(4), was doubled in BMMC from LTC(4)S (-/
      ) mice because of lack of utilization. The zymosan-elicited intraperitoneal
      extravasation of plasma protein and the IgE-mediated passive cutaneous
      anaphylaxis in the ear were significantly diminished in the LTC(4)S (-/-) mice.
      These observations indicate that LTC(4)S, but not microsomal or cytosolic
      glutathione S-transferases, is the major LTC(4)-producing enzyme in tissues and
      that its integrated function includes mediation of increased vascular
      permeability in either innate or adaptive immune host inflammatory responses.

PMID- 11319241
TI  - Neuroprotection by caffeine and A(2A) adenosine receptor inactivation in a model
      of Parkinson's disease.
AB  - Recent epidemiological studies have established an association between the common
      consumption of coffee or other caffeinated beverages and a reduced risk of
      developing Parkinson's disease (PD). To explore the possibility that caffeine
      helps prevent the dopaminergic deficits characteristic of PD, we investigated the
      effects of caffeine and the adenosine receptor subtypes through which it may act
      in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxin model of
      PD. Caffeine, at doses comparable to those of typical human exposure, attenuated
      MPTP-induced loss of striatal dopamine and dopamine transporter binding sites.
      The effects of caffeine were mimicked by several A(2A) antagonists (7-(2
      phenylethyl)-5-amino-2-(2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine
      (SCH 58261), 3,7-dimethyl-1-propargylxanthine, and (E)-1,3-diethyl-8 (KW-6002)
      (3,4-dimethoxystyryl)-7-methyl-3,7-dihydro-1H-purine-2,6-dione) (KW-6002) and by
      genetic inactivation of the A(2A) receptor, but not by A(1) receptor blockade
      with 8-cyclopentyl-1,3-dipropylxanthine, suggesting that caffeine attenuates MPTP
      toxicity by A(2A) receptor blockade. These data establish a potential neural
      basis for the inverse association of caffeine with the development of PD, and
      they enhance the potential of A(2A) antagonists as a novel treatment for this
      neurodegenerative disease.

PMID- 11319242
TI  - Enhancement by T-type Ca2+ currents of odor sensitivity in olfactory receptor
      cells.
AB  - Mechanisms underlying action potential initiation in olfactory receptor cells
      (ORCs) during odor stimulation were investigated using conventional and dynamic
      patch-clamp recording techniques. Under current-clamp conditions, action
      potentials generated by a least effective odor-induced depolarization were almost
      completely blocked by 0.1 mm Ni(2+), a T-type Ca(2+) channel blocker, but not by
      0.1 mm Cd(2+), a high voltage-activated Ca(2+) channel blocker. Under voltage
      clamp conditions, depolarizing voltage steps induced a fast transient inward
      current, which consisted of Na(+) (I(Na)) and T-type Ca(2+) (I(Ca,T)) currents.
      The amplitude of I(Ca,T) was approximately one-fourth of that of I(Na) (0.23 +/-
      0.03, mean +/- SEM). Because both I(Na) and I(Ca,T) are known to show rapid
      inactivation, we examined how much I(Na) and I(Ca,T) are activated during the
      gradually depolarizing initial phase of receptor potentials. The ratio of
      I(Ca,T)/I(Na) during a ramp depolarization at the slope of 0.5 mV/msec was 0.56
      +/- 0.03. Using the dynamic patch-clamp recording technique, we also recorded
      I(Ca,T) and I(Na) during the generation of odor-induced action potentials. This
      ratio of I(Ca,T)/I(Na) was 0.54 +/- 0.04. These ratios were more than twice as
      large as that (0.23) obtained from the experiment using voltage steps, suggesting
      that I(Ca,T) carries significant amount of current to generate the action
      potentials. We conclude that I(Ca,T) contributes to enhance odor sensitivity by
      lowering the threshold of spike generation in ORCs.

PMID- 11319243
TI  - Behavior-dependent states of the hippocampal network affect functional clustering
      of neurons.
AB  - Local versus distant coherence of hippocampal CA1 pyramidal cells was
      investigated in the behaving rat. Temporal cross-correlation of pyramidal cells
      revealed a significantly stronger relationship among local (<140 microm)
      pyramidal neurons compared with distant (>300 microm) neurons during non-theta
      associated immobility and sleep but not during theta-associated running and
      walking. In contrast, cross-correlation between local pyramidal cell-interneuron
      pairs was significantly stronger than between distant pairs during theta
      oscillations but were similar during non-theta-associated behaviors. We suggest
      that network state-dependent functional clustering of neuronal activity emerges
      because of the differential contribution of the main excitatory inputs, the
      perforant path, and Schaffer collaterals during theta and non-theta behaviors.

PMID- 11319244
TI  - Cannabinoids inhibit the formation of new synapses between hippocampal neurons in
      culture.
AB  - The principal psychoactive ingredient in marijuana, Delta(9)
      tetrahydrocannabinol, has been shown to inhibit adenylyl cyclase activity in
      vitro and can lead to impairment of memory in vivo. cAMP-induced changes in
      synaptic plasticity are thought to underlie memory formation. We examined the
      effects of cannabinoid receptor agonists on forskolin-induced formation of new
      synapses between rat hippocampal neurons in culture. Functional synaptic boutons
      were identified with FM1-43-based digital imaging. Cannabimimetic drugs prevented
      the recruitment of new synapses by inhibiting the formation of cAMP. The
      inhibition produced by Win55212-2, a synthetic cannabinoid receptor agonist, was
      stereoselective and was reversed by a selective CB1 receptor antagonist. Both
      Delta(9)-tetrahydrocannabinol and the endogenous ligand, anandamide, inhibited
      the formation of new synapses. Win55212-2 blocked the formation of new synapses
      induced by forskolin, but not those evoked by a membrane permeant cAMP analog.
      Thus, activation of cannabinoid receptors can modulate synaptic plasticity
      independent of direct effects on neurotransmitter release. Preventing the
      formation of new synapses may contribute to the impairment of memory produced by
      cannabinoids.

PMID- 11319246
TI  - Health-related quality of life following podiatric surgery.
AB  - This 6-month prospective study investigated the outcomes of foot surgery
      performed by Fellows of the Australian College of Podiatric Surgeons. The study
      recruited 140 patients who were treated for orthopedic, neurological, or
      integumentary diseases of the foot. The majority of subjects who underwent
      podiatric surgery experienced significant postoperative improvements in a range
      of health-related quality-of-life dimensions as measured by the disease-specific
      Foot Health Status Questionnaire (FHSQ) and the generic Short Form 36 (SF-36)
      questionnaire. Subjects reported a reduction in foot pain, increased levels of
      physical function, improved general foot health perception, and improved footwear
      related quality of life. No significant adverse outcomes or unplanned re
      admissions to the hospital were reported. This study demonstrates the advantage
      of assessing health-related quality of life as opposed to patient satisfaction.

PMID- 11319247
TI  - Foot orthosis prescription habits of Australian and New Zealand podiatric
      physicians.
AB  - This research project investigated the orthotic prescription habits of podiatric
      physicians in Australia and New Zealand. A 23-item questionnaire was distributed
      to all members of the Australian Podiatry Association and the New Zealand Society
      of Podiatrists. When asked what type of foot orthoses they prescribe most often,
      72% of respondents reported functional foot orthoses; the next most common
      response was prefabricated orthoses (12%). A typical prescription for functional
      foot orthoses consisted of a modified Root style orthosis, balanced to the
      neutral calcaneal stance position, with the shell made from polypropylene and an
      ethyl vinyl acetate (EVA) rearfoot post applied. The majority of podiatric
      physicians surveyed used a commercial orthotic laboratory to fabricate their
      orthoses. However, New Zealand respondents were three times more likely to
      prescribe prefabricated foot orthoses, and males were twice as likely as females
      to manufacture the orthoses themselves rather than use a commercial orthotic
      laboratory.

PMID- 11319248
TI  - Changes in foot function with the use of Root and Blake orthoses.
AB  - This study examined the effects of two designs of rigid foot orthoses on plantar
      pressure measurements and identified differences between the devices. While
      wearing modified Root- and Blake-style orthoses, 27 subjects were examined with
      the Electrodynogram (EDG) in-shoe pressure measurement system. Reliability
      testing was performed on the EDG data. Significant changes were observed in the
      temporal parameters of gait when subjects wore the orthoses. When the devices
      were used, the duration of some of the components of stance phase was altered,
      and the initiation of loading beneath the medial forefoot was delayed. A
      reduction in the total duration of loading at discrete sites beneath the heel and
      forefoot was also observed. The effects of the two orthoses were similar, with
      only small differences observed between the devices.

PMID- 11319249
TI  - Effects of prefabricated foot orthoses and soft insoles on postural stability in
      professional soccer players.
AB  - Postural stability is an important component of skilled athletic activity.
      However, the effects of foot orthoses on stability have not been adequately
      addressed. This study measured postural sway in 30 asymptomatic professional
      soccer players in three standing positions and four underfoot conditions. The
      results revealed that the underfoot condition had no significant effect on sway
      in the mediolateral or anteroposterior planes; however, there was a trend toward
      less mediolateral sway when subjects stood in a unipedal position with
      prefabricated orthoses. These results suggest that insoles and foot orthoses have
      no significant beneficial or detrimental effects on postural stability in
      asymptomatic subjects. Clinically, this suggests that no improvements in balance
      performance could be expected with prophylactic use of insoles or orthoses but
      that clinicians may prescribe insoles and foot orthoses without fear of impairing
      postural performance in elite athletes.

PMID- 11319250
TI  - A comparison of footprint indexes calculated from ink and electronic footprints.
AB  - Pressure platforms offer the potential to measure and record electronic
      footprints rapidly; however, the accuracy of geometric indexes derived from these
      prints has not been investigated. A comparison of conventional ink footprints
      with simultaneously acquired electronic prints revealed significant differences
      in several geometric indexes. The contact area was consistently underestimated by
      the electronic prints and resulted in a significant change in the arch index. The
      long plantar angle was poorly correlated between techniques. This study
      demonstrated that electronic footprints, derived from a pressure platform, are
      not representative of the equivalent ink footprints and, consequently, should not
      be interpreted with reference to literature on conventional footprints.

PMID- 11319251
TI  - Publication patterns and perceptions of the Australian podiatric medical faculty.
AB  - Despite the wide range of publication opportunities in podiatric medicine, little
      is known about how podiatric authors select journals in which to publish or their
      perceptions of journals currently available. To investigate these issues, a
      survey of publication patterns and perceptions of full- and part-time academic
      staff members at podiatric medical schools in Australia was undertaken. Most of
      the papers by Australian podiatric medical faculty members have been published in
      "local" journals, such as the Australasian Journal of Podiatric Medicine (38%)
      and the British Journal of Podiatry (17%). However, an increasing number of
      papers are being published in JAPMA (14%). In addition, a large proportion of
      papers have been published in a variety of journals that are not specific to
      podiatric medicine, particularly in the areas of biomechanics and diabetic
      medicine. The number of publications per faculty member was associated with the
      highest qualification obtained, academic rank, and the number of years of
      employment in higher education. The most important factors in selecting the
      journal in which to publish were the journal's inclusion in MEDLINE, the
      perceived prestige of the journal, and the quality of the journal's peer-review
      panel and editor.

PMID- 11319252
TI  - Medicare compliance for the podiatric medical practice.

PMID- 11319253
TI  - A general empirical model of protein evolution derived from multiple protein
      families using a maximum-likelihood approach.
AB  - Phylogenetic inference from amino acid sequence data uses mainly empirical models
      of amino acid replacement and is therefore dependent on those models. Two of the
      more widely used models, the Dayhoff and JTT models, are estimated using similar
      methods that can utilize large numbers of sequences from many unrelated protein
      families but are somewhat unsatisfactory because they rely on assumptions that
      may lead to systematic error and discard a large amount of the information within
      the sequences. The alternative method of maximum-likelihood estimation may
      utilize the information in the sequence data more efficiently and suffers from no
      systematic error, but it has previously been applicable to relatively few
      sequences related by a single phylogenetic tree. Here, we combine the best
      attributes of these two methods using an approximate maximum-likelihood method.
      We implemented this approach to estimate a new model of amino acid replacement
      from a database of globular protein sequences comprising 3,905 amino acid
      sequences split into 182 protein families. While the new model has an overall
      structure similar to those of other commonly used models, there are significant
      differences. The new model outperforms the Dayhoff and JTT models with respect to
      maximum-likelihood values for a large majority of the protein families in our
      database. This suggests that it provides a better overall fit to the evolutionary
      process in globular proteins and may lead to more accurate phylogenetic tree
      estimates. Potentially, this matrix, and the methods used to generate it, may
      also be useful in other areas of research, such as biological sequence database
      searching, sequence alignment, and protein structure prediction, for which an
      accurate description of amino acid replacement is required.

PMID- 11319254
TI  - Estimating divergence time with the use of microsatellite genetic distances:
      impacts of population growth and gene flow.
AB  - Genetic distances play an important role in estimating divergence time of
      bifurcated populations. However, they can be greatly affected by demographic
      processes, such as migration and population dynamics, which complicate their
      interpretation. For example, the widely used distance for microsatellite loci,
      (deltamu)2, assumes constant population size, no gene flow, and mutation-drift
      equilibrium. It is shown here that (deltamu)2 strongly underestimates divergence
      time if populations are growing and/or connected by gene flow. In recent
      publications, the average estimate of divergence time between African and non
      African populations obtained by using (deltamu)2 is about 34,000 years, although
      archaeological data show a much earlier presence of modern humans out of Africa.
      I introduce a different estimator of population separation time based on
      microsatellite statistics, T(D), that does not assume mutation-drift equilibrium,
      is independent of population dynamics in the absence of gene flow, and is robust
      to weak migration flow for growing populations. However, it requires a knowledge
      of the variance in the number of repeats at the beginning of population
      separation, V(0). One way to overcome this problem is to find minimal and maximal
      bounds for the variance and thus obtain the earliest and latest bounds for
      divergence time (this is not a confidence interval, and it simply reflects an
      uncertainty about the value of V(0) in an ancestral population). Another way to
      avoid the uncertainty is to choose from among present populations a reference
      whose variation is presumably close to what it might have been in an ancestral
      population. A different approach for using T(D) is to estimate the time
      difference between adjacent nodes on a phylogenetic population tree. Using data
      on variation at autosomal short tandem repeat loci with di-, tri-, and
      tetranucleotide repeats in worldwide populations, T(D) gives an estimate of
      57,000 years for the separation of the out-of-Africa branch of modern humans from
      Africans based on the value of V(0) in the Southern American Indian populations;
      the earliest bound for this event has been estimated to be about 135,000 years.
      The data also suggest that the Asian and European populations diverged from each
      other about 20,000 years, after the occurrence of the out-of-Africa branch.

PMID- 11319255
TI  - Pyruvate : NADP+ oxidoreductase from the mitochondrion of Euglena gracilis and
      from the apicomplexan Cryptosporidium parvum: a biochemical relic linking
      pyruvate metabolism in mitochondriate and amitochondriate protists.
AB  - Most eukaryotes perform the oxidative decarboxylation of pyruvate in mitochondria
      using pyruvate dehydrogenase (PDH). Eukaryotes that lack mitochondria also lack
      PDH, using instead the O(2)-sensitive enzyme pyruvate : ferredoxin oxidoreductase
      (PFO), which is localized either in the cytosol or in hydrogenosomes. The
      facultatively anaerobic mitochondria of the photosynthetic protist Euglena
      gracilis constitute a hitherto unique exception in that these mitochondria
      oxidize pyruvate with the O(2)-sensitive enzyme pyruvate : NADP oxidoreductase
      (PNO). Cloning and analysis of Euglena PNO revealed that the cDNA encodes a
      mitochondrial transit peptide followed by an N-terminal PFO domain that is fused
      to a C-terminal NADPH-cytochrome P450 reductase (CPR) domain. Two independent 5.8
      kb full-size cDNAs for Euglena mitochondrial PNO were isolated; the gene was
      expressed in cultures supplied with 2% CO(2) in air and with 2% CO(2) in N(2).
      The apicomplexan Cryptosporidium parvum was also shown to encode and express the
      same PFO-CPR fusion, except that, unlike E. gracilis, no mitochondrial transit
      peptide for C. parvum PNO was found. Recombination-derived remnants of PNO are
      conserved in the genomes of Saccharomyces cerevisiae and Schizosaccharomyces
      pombe as proteins involved in sulfite reduction. Notably, Trypanosoma brucei was
      found to encode homologs of both PFO and all four PDH subunits. Gene organization
      and phylogeny revealed that eukaryotic nuclear genes for mitochondrial,
      hydrogenosomal, and cytosolic PFO trace to a single eubacterial acquisition.
      These findings suggest a common ancestry of PFO in amitochondriate protists with
      Euglena mitochondrial PNO and Cryptosporidium PNO. They are also consistent with
      the view that eukaryotic PFO domains are biochemical relics inherited from a
      facultatively anaerobic, eubacterial ancestor of mitochondria and hydrogenosomes.

PMID- 11319256
TI  - Complete sequence of the mitochondrial genome of the tapeworm Hymenolepis
      diminuta: gene arrangements indicate that Platyhelminths are Eutrochozoans.
AB  - Using "long-PCR," we amplified in overlapping fragments the complete
      mitochondrial genome of the tapeworm Hymenolepis diminuta (Platyhelminthes:
      Cestoda) and determined its 13,900-nt sequence. The gene content is the same as
      that typically found for animal mitochondrial DNA (mtDNA) except that atp8
      appears to be lacking, a condition found previously for several other animals.
      Despite the small size of this mtDNA, there are two large noncoding regions, one
      of which contains 13 repeats of a 31-nt sequence and a potential stem-loop
      structure of 25 bp with an 11-member loop. Large potential secondary structures
      were identified also for the noncoding regions of two other cestode mtDNAS:
      Comparison of the mitochondrial gene arrangement of H. diminuta with those
      previously published supports a phylogenetic position of flatworms as members of
      the Eutrochozoa, rather than placing them basal to either a clade of protostomes
      or a clade of coelomates.

PMID- 11319257
TI  - Microsatellite variation in colonizing and palearctic populations of Drosophila
      subobscura.
AB  - The recent colonization of North America by Drosophila subobscura has provided a
      great opportunity to analyze a colonization process from the beginning. A
      comparative study using 10 microsatellite loci was conducted for five European
      and two North American populations. No genetic differentiation between European
      populations was detected, indicating that gene flow is high among them and that
      the microsatellites used in the present work represent neutral markers not
      subject to differentiation due to selection. Extensive reduction in the number of
      alleles and a significant decrease in heterozygosity in colonizing populations
      were detected that could be explained by the founder effect and a subsequent
      quick but not infinite expansion. Assuming that all alleles present in the
      colonized area were carried by the sample of colonizers, we estimated that most
      probably 4-11 individuals expanded in the new area. F(ST) and the chord distance
      measures reflect the colonization process more accurately, since drift has been
      the major force in differentiating the Old and New World populations, and thus
      other measures considering allele size differences, such as Rho(ST) and deltamu2,
      are less reliable for studying nonequilibrium populations. Finally, our results
      were consistent with the two-phase microsatellite mutational model, indicating
      that most alleles are generated by gain or loss of a repeat unit, while some
      alleles originate by more complex mutations.

PMID- 11319258
TI  - Patterns of temperature adaptation in proteins from the bacteria Deinococcus
      radiodurans and Thermus thermophilus.
AB  - Asymmetrical patterns of amino acid substitution in proteins of organisms living
      at moderate and high temperatures (mesophiles and thermophiles, respectively) are
      generally taken to indicate selection favoring different amino acids at different
      temperatures due to their biochemical properties. If that were the case,
      comparisons of different pairs of mesophilic and thermophilic taxa would exhibit
      similar patterns of substitutional asymmetry. A previous comparison of mesophilic
      versus thermophilic Methanococcus with mesophilic versus thermophilic Bacillus
      revealed several pairs of amino acids for which one amino acid was favored in
      thermophilic Bacillus and the other was favored in thermophilic Methanococcus.
      Most of this could be explained by the higher G+C content of the DNA of
      thermophilic Bacillus, a phenomenon not seen in the Methanococcus comparison.
      Here, I compared the mesophilic bacterium Deinococcus radiodurans and its
      thermophilic relative Thermus thermophilus, which are similar in G+C content. Of
      the 190 pairs of amino acids, 83 exhibited significant substitutional asymmetry,
      consistent with the pervasive effects of selection. Most of these significantly
      asymmetrical pairs of amino acids were asymmetrical in the direction predicted
      from the Methanococcus data, consistent with thermal adaptation resulting from
      universal biochemical properties of the amino acids. However, 12 pairs of amino
      acids exhibited asymmetry significantly different from and in the opposite
      direction of that found in the Methanococcus comparison, and 21 pairs of amino
      acids exhibited asymmetry that was significantly different from that found in the
      Bacillus comparison and could not be explained by the greater G+C content in
      thermophilic Bacillus. This suggests that selection due to universal biochemical
      properties of the amino acids and differences in G+C content are not the only
      causes of substitutional asymmetry between mesophiles and thermophiles. Instead,
      selection on taxon-specific properties of amino acids, such as their metabolic
      cost, may play a role in causing asymmetrical patterns of substitution.

PMID- 11319259
TI  - Structural constraints and emergence of sequence patterns in protein evolution.
AB  - The aim of this work was to study the relationship between structure conservation
      and sequence divergence in protein evolution. To this end, we developed a model
      of structurally constrained protein evolution (SCPE) in which trial sequences,
      generated by random mutations at gene level, are selected against departure from
      a reference three-dimensional structure. Since at the mutational level SCPE is
      completely unbiased, any emergent sequence pattern will be due exclusively to
      structural constraints. In this first report, it is shown that SCPE correctly
      predicts the characteristic hexapeptide motif of the left-handed parallel beta
      helix (LbetaH) domain of UDP-N-acetylglucosamine acyltransferases (LpxA).

PMID- 11319260
TI  - The elevated GC content at exonic third sites is not evidence against neutralist
      models of isochore evolution.
AB  - The human genome is divided into isochores, large stretches (>>300 kb) of genomic
      DNA with more or less consistent GC content. Mutational/neutralist and
      selectionist models have been put forward to explain their existence. A major
      criticism of the mutational models is that they cannot account for the higher GC
      content at fourfold-redundant silent sites within exons (GC4) than in flanking
      introns (GCi). Indeed, it has been asserted that it is hard to envisage a
      mutational bias explanation, as it is difficult to see how repair enzymes might
      act differently in exons and their flanking introns. However, this rejection, we
      note, ignores the effects of transposable elements (TEs), which are a major
      component of introns and tend to cause them to have a GC content different from
      (usually lower than) that dictated by point mutational processes alone. As TEs
      tend not to insert at the extremities of introns, this model predicts that GC
      content at the extremities of introns should be more like that at GC4 than are
      the intronic interiors. This we show to be true. The model also correctly
      predicts that small introns should have a composition more like that at GC4 than
      large introns. We conclude that the logic of the previous rejection of neutralist
      models is unsafe.

PMID- 11319261
TI  - A dependent-rates model and an MCMC-based methodology for the maximum-likelihood
      analysis of sequences with overlapping reading frames.
AB  - We present a model and methodology for the maximum-likelihood analysis of
      pairwise alignments of DNA sequences in which two genes are encoded in
      overlapping reading frames. In the model for the substitution process, the
      instantaneous rates of substitution are allowed to depend on the nucleotides
      occupying the sites in a neighborhood of the site subject to substitution at the
      instant of the substitution. By defining the neighborhood of a site to extend
      over all sites in the codons in both reading frames to which a site belongs,
      constraints imposed by the genetic code in both reading frames can be taken into
      account. Due to the dependency of the instantaneous rates of substitution on the
      states at neighboring sites, the transition probability between sequences does
      not factorize and therefore cannot be obtained directly. We present a Markov
      chain Monte Carlo procedure for obtaining the ratio of two transition
      probabilities between two sequences under the model considered, and we describe
      how maximum-likelihood parameter estimation and likelihood ratio tests can be
      performed using the procedure. We describe how the expected numbers of different
      types of substitutions in the shared history of two sequences can be calculated,
      and we use the described model and methodology in an analysis of a pairwise
      alignment of two hepatitis B sequences in which two genes are encoded in
      overlapping frames. Finally, we present an extended model, together with a
      simpler approximate estimation procedure, and use this to test the adequacy of
      the former model.

PMID- 11319262
TI  - Molecular phylogeny and divergence time estimates for major rodent groups:
      evidence from multiple genes.
AB  - The order Rodentia contains half of all extant mammal species, and from an
      evolutionary standpoint, there are persistent controversies surrounding the
      monophyly of the order, divergence dates for major lineages, and relationships
      among families. Exons of growth hormone receptor (GHR) and breast cancer
      susceptibility (BRCA1) genes were sequenced for a wide diversity of rodents and
      other mammals and combined with sequences of the mitochondrial 12S rRNA gene and
      previously published sequences of von Willebrand factor (vWF). Rodents exhibit
      rates of amino acid replacement twice those observed for nonrodents, and this
      rapid rate of evolution influences estimates of divergence dates. Based on GHR
      sequences, monophyly is supported, with the estimated divergence between
      hystricognaths and most sciurognaths dating to about 75 MYA. Most estimated dates
      of divergence are consistent with the fossil record, including a date of 23 MYA
      for Mus-Rattus divergence. These dates are considerably later than those derived
      from some other molecular studies. Among combined and separate analyses of the
      various gene sequences, moderate to strong support was found for several clades.
      GHR appears to have greater resolving power than do 12S or vWF. Despite its
      complete unresponsiveness to growth hormone, Cavia (and other hystricognaths)
      exhibits a conservative rate of change in the intracellular domain of GHR.

PMID- 11319263
TI  - Analysis of codon usage patterns of bacterial genomes using the self-organizing
      map.
AB  - Codon usage varies both between organisms and between different genes in the same
      organism. This observation has been used as a basis for earlier work in
      identifying highly expressed and horizontally transferred genes in Escherichia
      coli. In this work, we applied Kohonen's self-organizing map to analysis of the
      codon usage pattern of the Escherichia coli, Aquifex aeolicus, Archaeoglobus
      fulgidus, Haemophilus influenzae RD:, Methanococcus jannaschii, Methanobacterium
      thermoautotrophicum, and Pyrococcus horikoshii genomes for evidence of highly
      expressed genes and horizontally transferred genes. All of the analyzed genomes
      had a clear category of horizontally transferred genes, and their apparent
      percentages ranged from 7.7% to 21.4%. The apparent percentage of highly
      expressed genes ranges from 0% to 11.8%. A clustering of average codon usage of
      main gene categories of the seven genomes showed an interesting mixing of gene
      classes in four thermophilic/hyperthermophilic organisms, A. aeolicus, A.
      fulgidus, M. thermoautotrophicum, and P. horikoshii, which suggests possible
      origins of their horizontally transferred genes as well as the need for
      adaptation to a specific environment. Further classification of the three gene
      categories in E. coli and H. influenzae according to gene function revealed that
      genes involved in communication (such as regulation and cell process) and
      structure (cell structure and structural proteins) are more likely to be
      horizontally transferred than are genes involved in information (transcription,
      translation, and related processes) and in some groups of energy (such as energy
      metabolism and carbon compound catabolism).

PMID- 11319264
TI  - Molecular evolution of the ocnus and janus genes in the Drosophila melanogaster
      species subgroup.
AB  - Genes involved in male fertility are potential targets for sexual selection, and
      their evolution may play a role in reproductive isolation and speciation. Here we
      describe a new Drosophila melanogaster gene, ocnus (ocn), that encodes a protein
      abundant in testes nuclear extracts. RT-PCR indicates that ocn transcription is
      limited to males and is specific to testes. ocn shares homology with another
      testis-specific gene, janusB (janB), and is located just distal to janB on
      chromosome 3. The two genes also share homology with the adjacent janusA (janA)
      gene, suggesting that multiple duplication events have occurred within this
      region of the genome. We cloned and sequenced these three genes from species of
      the D. melanogaster species subgroup. Phylogenetic analysis based on protein
      encoding sequences predicts a duplication pattern of janA --> janA janB --> janA
      janB ocn, with the latter event occurring after the divergence of the D.
      melanogaster and Drosophila obscura species groups. We found significant
      heterogeneity in the rates of evolution among the three genes within the D.
      melanogaster species subgroup as measured by the ratio of nonsynonymous to
      synonymous substitutions, suggesting that diversification of gene function
      followed each duplication event and that each gene evolved under different
      selective constraints. All three genes showed faster rates of evolution than
      genes encoding proteins with metabolic function. These results are consistent
      with previous studies that have detected an increased rate of evolution in genes
      with reproductive function.

PMID- 11319265
TI  - A new theory of phylogeny inference through construction of multidimensional
      vector space.
AB  - Here, a new theory of molecular phylogeny is developed in a multidimensional
      vector space (MVS). The molecular evolution is represented as a successive
      splitting of branch vectors in the MVS. The end points of these vectors are the
      extant species and indicate the specific directions reflected by their individual
      histories of evolution in the past. This representation makes it possible to
      infer the phylogeny (evolutionary histories) from the spatial positions of the
      end points. Search vectors are introduced to draw out the groups of species
      distributed around them. These groups are classified according to the nearby
      order of branches with them. A law of physics is applied to determine the species
      positions in the MVS. The species are regarded as the particles moving in time
      according to the equation of motion, finally falling into the lowest-energy state
      in spite of their randomly distributed initial condition. This falling into the
      ground state results in the construction of an MVS in which the relative
      distances between two particles are equal to the substitution distances. The
      species positions are obtained prior to the phylogeny inference. Therefore, as
      the number of species increases, the species vectors can be more specific in an
      MVS of a larger size, such that the vector analysis gives a more stable and
      reliable topology. The efficacy of the present method was examined by using
      computer simulations of molecular evolution in which all the branch- and end
      point sequences of the trees are known in advance. In the phylogeny inference
      from the end points with 100 multiple data sets, the present method consistently
      reconstructed the correct topologies, in contrast to standard methods. In
      applications to 185 vertebrates in the alpha-hemoglobin, the vector analysis drew
      out the two lineage groups of birds and mammals. A core member of the mammalian
      radiation appeared at the base of the mammalian lineage. Squamates were isolated
      from the bird lineage to compose the outgroup, while the other living reptilians
      were directly coupled with birds without forming any sister groups. This result
      is in contrast to the morphological phylogeny and is also different from those of
      recent molecular analyses.

PMID- 11319266
TI  - Pseudogenes, junk DNA, and the dynamics of Rickettsia genomes.
AB  - Studies of neutrally evolving sequences suggest that differences in eukaryotic
      genome sizes result from different rates of DNA loss. However, very few
      pseudogenes have been identified in microbial species, and the processes whereby
      genes and genomes deteriorate in bacteria remain largely unresolved. The typhus
      causing agent, Rickettsia prowazekii, is exceptional in that as much as 24% of
      its 1.1-Mb genome consists of noncoding DNA and pseudogenes. To test the
      hypothesis that the noncoding DNA in the R. prowazekii genome represents degraded
      remnants of ancestral genes, we systematically examined all of the identified
      pseudogenes and their flanking sequences in three additional Rickettsia species.
      Consistent with the hypothesis, we observe sequence similarities between genes
      and pseudogenes in one species and intergenic DNA in another species. We show
      that the frequencies and average sizes of deletions are larger than insertions in
      neutrally evolving pseudogene sequences. Our results suggest that inactivated
      genetic material in the Rickettsia genomes deteriorates spontaneously due to a
      mutation bias for deletions and that the noncoding sequences represent DNA in the
      final stages of this degenerative process.

PMID- 11319267
TI  - Evolution of endogenous retrovirus-like elements of the woolly mammoth (Mammuthus
      primigenius) and its relatives.
AB  - Endogenous retrovirus-like elements characterizable by a leucine tRNA primer (ERV
      Ls) are reiterated genomic sequences known to be widespread in mammals, including
      humans. They may have arisen from an ancestral foamy virus-like element by
      successful germ line infection followed by copy number expansion. However, among
      mammals, only primates and rodents have thus far exhibited high copy number
      amplification and sequence diversification. Conventionally, empirical studies of
      proviral amplification and diversification have been limited to extant species,
      but taxa having good Quaternary fossil records could potentially be investigated
      using the techniques of "ancient" DNA research. To examine evolutionary
      parameters of ERV-Ls across both time and taxa, we characterized this proviral
      class in the extinct woolly mammoth (Mammuthus primigenius) and living elephants,
      as well as extant members of the larger clade to which they belong (Uranotheria,
      a group containing proboscideans, sirenians, hyraxes, and their extinct
      relatives). Ungulates and carnivores previously analyzed demonstrated low copy
      numbers of ERV-L sequences, and thus it was expected that uranotheres should as
      well. Here, we show that all uranothere taxa exhibit unexpectedly numerous and
      diverse ERV-L sequence complements, indicating active expansion within this group
      of lineages. Selection is the most parsimonious explanation for observed
      differences in ERV-L distribution and frequency, with relative success being
      reflected in the persistence of certain elements over a variety of sampled time
      depths (as can be observed by comparing sequences from fossil and extant
      elephantid samples).

PMID- 11319268
TI  - Structural and phylogenetic analysis of TRAS, telomeric repeat-specific non-LTR
      retrotransposon families in Lepidopteran insects.
AB  - TRAS1 is a non-LTR retrotransposon inserted specifically into the telomeric
      repeat (TTAGG)(n) in the silkworm, Bombyx mori. To characterize the evolutionary
      origin of TRAS-like elements, we identified seven TRAS families (TRAS3, TRAS4,
      TRAS5, TRAS6, TRASY, TRASZ, and TRASW) from B. mori and four elements from two
      Lepidoptera, Dictyoploca japonica (TRASDJ) and Samia cynthia ricini (TRASSC3,
      TRASSC4, and TRASSC9). More than 2,000 copies of various Bombyx TRAS elements
      accumulated within (TTAGG)(n) sequences as unusual but orderly tandem repeats.
      The 5' and 3' regions were highly conserved within each class of Bombyx TRAS
      elements without truncation. This suggests that distinct classes of TRAS have
      been maintained independently by retrotransposition into (TTAGG)(n). The
      phylogenetic tree of site-specific retroelements showed that nine TRAS families
      in Lepidoptera constitute a single phylogenetic group that is closely related to
      the R1 family that inserts specifically into arthropod 28S rDNA. The higher amino
      acid sequence identity from endonuclease (EN) to reverse transcriptase (RT)
      domains between TRAS groups (about 37%-70%) than among TRAS elements and R1Bm
      (about 25%-30%), may reflect the presence of some DNA structure responsible for
      their target specificity. Sequence comparison from EN to RT domains among non-LTR
      elements revealed several regions conserved only within TRAS elements. We found a
      highly conserved region that resembles the Myb-like DNA-binding structure,
      between the EN and RT domains. These regions may be involved in site-specific
      integration of TRAS elements into the (TTAGG)(n) telomeric repeats.

PMID- 11319269
TI  - Numerous gene rearrangements in the mitochondrial genome of the wallaby louse,
      Heterodoxus macropus (Phthiraptera).
AB  - The complete arrangement of genes in the mitochondrial (mt) genome is known for
      12 species of insects, and part of the gene arrangement in the mt genome is known
      for over 300 other species of insects. The arrangement of genes in the mt genome
      is very conserved in insects studied, since all of the protein-coding and rRNA
      genes and most of the tRNA genes are arranged in the same way. We sequenced the
      entire mt genome of the wallaby louse, Heterodoxus macropus, which is 14,670 bp
      long and has the 37 genes typical of animals and some noncoding regions. The
      largest noncoding region is 73 bp long (93% A+T), and the second largest is 47 bp
      long (92% A+T). Both of these noncoding regions seem to be able to form stem-loop
      structures. The arrangement of genes in the mt genome of this louse is unlike
      that of any other animal studied. All tRNA genes have moved and/or inverted
      relative to the ancestral gene arrangement of insects, which is present in the
      fruit fly Drosophila yakuba. At least nine protein-coding genes (atp6, atp8,
      cox2, cob, nad1-nad3, nad5, and nad6) have moved; moreover, four of these genes
      (atp6, atp8, nad1, and nad3) have inverted. The large number of gene
      rearrangements in the mt genome of H. macropus is unprecedented for an arthropod.

PMID- 11319270
TI  - Maximum-likelihood phylogenetic analysis under a covarion-like model.
AB  - Here, a model allowing covarion-like evolution of DNA sequences is introduced. In
      contrast to standard representation of the distribution of evolutionary rates,
      this model allows the site-specific rate to vary between lineages. This is
      achieved by adding as few as two parameters to the widely used among-site rate
      variation model, namely, (1) the proportion of sites undergoing rate changes and
      (2) the rate of rate change. This model is implemented in the likelihood
      framework, allowing parameter estimation, comparison of models, and tree
      reconstruction. An application to ribosomal RNA sequences suggests that covarions
      (i.e., site-specific rate changes) play an important role in the evolution of
      these molecules. Neglecting them results in a severe underestimate of the
      variance of rates across sites. It has, however, little influence on the
      estimation of ancestral G+C contents obtained from a nonhomogeneous model, or on
      the resulting inferences about the evolution of thermophyly. This theoretical
      effort should be useful for the study of protein adaptation, which presumably
      proceeds in a typical covarion-like manner.

PMID- 11319271
TI  - Elevated rates of nonsynonymous substitution in island birds.
AB  - Slightly deleterious mutations are expected to fix at relatively higher rates in
      small populations than in large populations. Support for this prediction of the
      nearly-neutral theory of molecular evolution comes from many cases in which
      lineages inferred to differ in long-term average population size have different
      rates of nonsynonymous substitution. However, in most of these cases, the
      lineages differ in many other ways as well, leaving open the possibility that
      some factor other than population size might have caused the difference in
      substitution rates. We compared synonymous and nonsynonymous substitutions in the
      mitochondrial cyt b and ND2 genes of nine closely related island and mainland
      lineages of ducks and doves. We assumed that island taxa had smaller average
      population sizes than those of their mainland sister taxa for most of the time
      since they were established. In all nine cases, more nonsynonymous substitutions
      occurred on the island branch, but synonymous substitutions showed no significant
      bias. As in previous comparisons of this kind, the lineages with smaller
      populations might differ in other respects that tend to increase rates of
      nonsynonymous substitution, but here such differences are expected to be slight
      owing to the relatively recent origins of the island taxa. An examination of
      changes to apparently "preferred" and "unpreferred" synonymous codons revealed no
      consistent difference between island and mainland lineages.

PMID- 11319272
TI  - Structural and evolutionary analysis of the copia-like elements in the
      Arabidopsis thaliana genome.
AB  - The analysis of 460 kb of genomic sequence of Arabidopsis thaliana chromosome III
      allowed us to identify two new transposable elements named AtC1 and AtC2. AtC1
      shows identical long terminal repeats (LTRs) and all the structural features
      characteristic of the copia-like active elements. AtC2 is also a full copia-like
      element, but a putative stop codon in the open reading frame (ORF) would produce
      a truncated protein. In order to identify the copia-like fraction of the A.
      thaliana genome, a careful computer-based analysis of the available sequences
      (which correspond to 92% of the genome) was performed. Approximately 300
      nonredundant copia-like sequences homologous to AtC1 and AtC2 were detected,
      which showed an extreme heterogeneity in size and degree of conservation. This
      number of copies would correspond to approximately 1% of the A. thaliana genome.
      Seventy-one sequences were selected for further analysis, with 23 of them being
      full complete elements. Five corresponded to previously described ones, and the
      remaining ones, named AtC3 to AtC18 are new elements described in this work. Most
      of these elements presented a putative functional ORF, nearly identical LTRs, and
      the other elements necessary for retrotransposon activity. Phylogenetic trees,
      supported by high bootstrap values, indicated that these 23 elements could be
      considered separate families. In turn, these 23 families could be clustered into
      six major lineages, named copia I-VI. Most of the 71 analyzed sequences clustered
      into these six main clades. The widespread presence of these copia-like
      superfamilies throughout plant genomes is discussed.

PMID- 11319273
TI  - Microuli, a family of miniature subterminal inverted-repeat transposable elements
      (MSITEs): transposition without terminal inverted repeats.

PMID- 11319274
TI  - Opacification of isolated rat lenses intoxicated with diethylmaleate: relation to
      lens membrane dysfunction.
AB  - We examined whether opacification of rat lenses treated with diethylmaleate
      (DEM), a depletor of reduced glutathione (GSH), is associated with membrane
      dysfunction. When isolated rat lenses were incubated with 2 mM DEM for 1, 6, and
      24 h, a cortical opacity appeared at 6 h and was more pronounced at 24 h. This
      opacification was accompanied by decreases in GSH and vitamin E (Vit. E) content
      and Na+,K+-ATPase activity, and an increase in water content, but not by a change
      in the content of thiobarbituric acid reactive substances (TBARS), an index of
      lipid peroxidation. Vit. E co-treatment caused a partial prevention of
      opacification, a complete recovery of decreased Vit. E content, attenuation of
      decreased Na+,K+-ATPase activity, and a decrease in TBARS content in rat lenses
      treated with 2 mM DEM for 24 h. Neither opacity formation nor changes in Vit. E,
      TBARS, and water content and Na+,K+-ATPase activity occurred in rat lenses
      treated for 48 h with 2 mM l-buthionine-(S,R)-sulfoximine, an inhibitor of
      glutathione synthesis, although a marked GSH depletion was observed. These
      results suggest that opacification of isolated rat lenses treated with DEM could
      be associated with impairment of Na+,K+-ATPase rather than GSH depletion.

PMID- 11319275
TI  - N-acetyl-L-cysteine simultaneously increases mitogenesis and suppresses apoptosis
      in mitogen-stimulated B-lymphocytes from p53 haploinsufficient Tg.AC (v-Ha-ras)
      mice.
AB  - Recent epidemiological evidence suggests that antioxidants may enhance
      carcinogenesis by promoting cellular proliferation and/or impeding programmed
      cell death. We examined the effect of N-acetyl-l-cysteine (NAC) on mitogenesis
      and apoptosis in splenocytes from p53 haploinsufficient Tg.AC (v-Ha-ras) mice.
      This model contains genetic lesions found frequently in human cancer and is
      predisposed to develop carcinogen-induced cancer. Splenocytes were incubated with
      NAC alone or with the B- and T-cell-specific mitogens Concanavalin A (Con A) and
      E. coli lipopolysaccharide (LPS), respectively. Mitogenesis increased 17-fold in
      mitogen-stimulated cultures and 10-fold in cultures incubated with NAC alone. Co
      incubation with both NAC (1000 microg/mL) and mitogen increased mitogenesis by 33
      fold without changing apoptosis rates. Strikingly, incubation with NAC and LPS
      attenuated LPS-induced apoptosis. Mitogen alone did not affect GSH levels but NAC
      induced increases were significantly depleted by co-incubation with mitogen.
      Furthermore, NAC increased the number of CD45R+ B cells, but decreased CD3+ T
      cells showing enhanced survival of B cells under these conditions. These results
      demonstrate concurrent reduced apoptosis and increased mitogenesis in B
      lymphocytes that may favor clonal selection of preneoplastic cells.

PMID- 11319276
TI  - Human neuroblastoma cell viability and growth are affected by altered culture
      conditions.
AB  - The effects of differing culture parameters are seldomly investigated, even
      though they influence the way immortalized cells grow and die. In this study, the
      changes in total cell number, confluency, membrane permeability, and DNA content
      were evaluated in SH-SY5Y and IMR-32 human neuroblastoma cells following culture
      at different seeding densities and media consistencies. These four endpoints were
      determined using a hemacytometer, phase-contrast microscope, trypan blue (0.4%
      v/v), and propidium iodide (50 microg/mL), respectively. Both cell lines (SH-SY5Y
      and IMR-32) responded in a similar manner to changing culture conditions, even
      though baseline values for all four endpoints were different. Higher seeding
      densities (19,200 and 38,400 cells/cm2) significantly increased the percent
      confluency and total cell number over time, but decreased the initial percentage
      of cells with fragmented (subG1) DNA in both cell lines when compared with lower
      seeding densities (4800 and 9600 cells/cm2, p < 0.05). Daily media changes
      significantly increased the percentage of cells in S and G2/M, but decreased the
      percentage of cells in G0/G1 phase of the cell cycle over time in both cell lines
      when compared with cultures without media changes (p < 0.05). Results suggest
      that environmental culture conditions greatly affect cellular mitosis and death.
      This information may be of particular relevance in the investigation of compounds
      that act on specific cell-cycle stages, such as antineoplastic agents.

PMID- 11319277
TI  - Trimethyltin reduces ATP levels and MTT reduction in the LRM55 rat astrocytoma
      cell line.
AB  - The LRM55 rat astrocytoma cell line was used to study the time and concentration
      effects of trimethyltin (TMT) exposure on intracellular adenosine triphosphate
      (ATP) levels, formazan production from (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl
      tetrazolium bromide (MTT), and lactate dehydrogenase (LDH) release. TMT
      concentrations of > or =50 microM produced a delayed increase in extracellular
      LDH from approximately 20% at 24 h to almost 70%, at 72 h. Twenty-four hours
      before cell lysis was detectable ATP levels decreased to less than 30% and
      formazan production declined to 70% (50 microM), 31% (100 microM), and 21% (200
      microM) of control values. Concentrations of TMT (5 and 10 microM) that produced
      little or no LDH release also decreased ATP levels (62 and 49% of control,
      respectively) and formazan production (63 and 52% of control, respectively) by 48
      h. These data support the hypothesis that TMT exposure interferes with energy
      production and that this event likely contributes to the delayed cell death seen
      in this cell line. Moreover, the declines in ATP and formazan production can
      occur at subtoxic concentrations in LRM55 cells.

PMID- 11319278
TI  - Radical generation, radical-scavenging activity, and cytotoxicity of eugenol
      related compounds.
AB  - To clarify the possible link between radicals and cytotoxicity of eugenol-related
      compounds, dimeric compounds were synthesized from eugenol (4-allyl-2-methoxy
      phenol), butylated hydroxyanisole (BHA) (2-t-butyl-4-methoxyphenol) or MMP (2
      methoxy-4-methylphenol); bis-EUG (3,3'-dimethoxy-5,5'-di-2-propenyl-1,1'-biphenyl
      2,2'-diol), bis-BHA (3,3'-di-t-butyl-5,5'-dimethoxy-1,1'-biphenyl-2,2'-diol), and
      bis-MMP (3,3'-di-methoxy-5,5'-dimethyl-1,1'-biphenyl-2,2'-diol). The cytotoxic
      activity of these compounds was determined using a salivary gland tumor cell line
      (HSG), oral squamous cell carcinoma cell line (HSC-2) and human promyelocytic
      leukemia cell line (HL-60). A parabolic relationship between the cytotoxicity and
      log P (the octanol-water partition coefficient) was observed, showing that both
      BHA and bis-MMP, with a log P of 3-4, were the most cytotoxic. The cytotoxic
      activity of the 2-methoxy derivatives, eugenol, MMP and bis-MMP, against HSG
      cells was significantly enhanced by visible-light irradiation, possibly due to
      their high redox potential. Electron spin resonance (ESR) spectroscopy indicated
      that eugenol and BHA alone produced radicals under alkaline conditions (pH >
      9.5), and eugenol most efficiently scavenges reactive oxygen species (O2-).
      Antioxidative reactivity of eugenol-related compounds was determined by measuring
      the inhibiting periods of the AIBN (2,2'-azobisisobutyronitrile)/MMA (methyl
      methacrylate) polymerization system, and the number of moles of peroxy radical
      trapped by moles of the relevant phenols (stoichiometric factor, n). It was found
      that the n values of eugenol and MMP were approximately 1, whereas those of BHA
      >2, suggesting that eugenol and MMP undergo dimerization through radical-radical
      couplings through quinone methides, whereas BHA undergoes the competitive
      interaction with poly-MMA radicals after oxidation by AIBN-peroxy radicals. BHA
      was an efficient peroxy radical-scavenger, but possibly reacted with polymer
      radicals of the lipid, thus mediating the cytotoxicity. The n value of bis-BHA
      was two, whereas those of bis-EUG and bis-MMP were 1.6-1.7, suggesting that the
      latter were further oxidized. The enthalpies of phenoxyl radical formation were
      determined using the semi-empirical PM3 quantum-mechanical method and the
      possible link to redox potential was discussed.

PMID- 11319279
TI  - Comparison of in vitro and in utero ethanol exposure on indices of oxidative
      stress.
AB  - Prenatal ethanol exposure produces neural tube defects and growth retardation in
      experimental animals. Because ethanol's teratogenic effects may involve oxidative
      stress and effects may differ in vitro and in utero, glutathione, cysteine and
      ATP were evaluated in gestational day 10 rat conceptuses exposed to ethanol.
      Cultured embryos exposed to ethanol (1.5 or 3.0 mg/mL) maintained a concentration
      dependent decrease in glutathione of 21 or 35%, respectively, at 6 h; visceral
      yolk sac (VYS) glutathione (GSH) decreased by 22 or 18%, respectively, at 3 h.
      Maternal ethanol exposure (4.5 g/kg) decreased glutathione by 30% in embryos and
      VYSs at 3 h, but values rebounded. Cultured embryonic cysteine decreased after 30
      min by 42% with both doses and after 6 h by 32 or 38% with 1.5 or 3.0 mg/mL,
      respectively. Ethanol (1.5 mg/mL) increased VYS cysteine by 35% after 30 min. In
      utero ethanol exposure decreased embryonic cysteine by 58% at 3 h. Ethanol (1.5
      mg/mL) decreased adenosine triphosphate (ATP) by 30-60% in embryos and VYSs at 30
      min. After 6 h, embryonic ATP decreased by 41 and 30% with 1.5 and 3.0 mg/mL,
      respectively, while VYS ATP decreased by 38% with 1.5 mg/mL. In utero ethanol
      exposure decreased ATP by 31% at 3 h in VYSs. While decreases in GSH and cysteine
      were evident earlier in utero than in vitro, values returned to control
      suggesting embryos exposed in utero respond rapidly to chemical-induced oxidative
      stress due to maternal protective mechanisms. Differences between in vitro and in
      utero responses to ethanol have important implications for interpretation of in
      vitro developmental studies.

PMID- 11319280
TI  - Improved overall survival among responders to preoperative chemoradiation for
      locally advanced rectal cancer.
AB  - The aim of this study was to determine if the response to preoperative radiation
      and chemotherapy with continuous infusion 5-fluorouracil (5-FU) was predictive
      for survival among patients with locally advanced rectal cancer. Preoperative
      chemoradiation (CTX/XRT) that delivered 45 Gy in 25 fractions over 5 weeks with
      continuous infusion 5-FU (300 mg/m2/day) was given to 117 patients. The
      pretreatment stage distribution, as determined by endorectal ultrasound (u),
      included uT2N0 in 2%, uT3N0 in 47%, uT3N1 in 49%, and uT4N0 in 2% of cases;
      endorectal ultrasound was not performed in 13% of cases (15 patients).
      Approximately 6 weeks after completion of CTX/XRT, surgery was performed.
      Adjuvant chemotherapy, consisting of 400 to 425 mg/m2 of 5-FU plus 20 mg/m2
      leucovorin for 5 days, was administered every 28 days for 4 to 6 cycles after
      surgical resection. Among the 74 patients treated with adjuvant chemotherapy, the
      preoperative stage of disease was 31 with T3N0 and 43 T3N1. Median follow-up was
      46 months (range 2 to 89 months). The pathologic tumor stages were Tis-2N0 in
      26%, T2N1 in 5%, T3N0 in 21%, T3N1 in 15%, T4N0 in 5%, and T4N1 in 1%; a complete
      response (CR) to preoperative CTX/XRT was pathologically confirmed in 32 (27%) of
      patients. Tumor down-staging occurred in 72 (62%) cases. A sphincter-saving
      procedure (SP) was possible in 59% of patients. The median DFS and overall
      survival rates for responders were 46 months and 47 months, respectively; for non
      responders these outcome measures were 38 months and 41 months, respectively. Log
      rank analysis showed that the distant metastatic-free survival rates improved
      with any response to CTX/XRT (p < 0.00001), CR to CTX/XRT (p < 0.009) and SP (p <
      0.012). Likewise, these parameters also significantly influenced DFS rates
      (CTX/XRT p < 0.00001; CR p < 0.006; and SP p < 0.008). Control of pelvic disease
      was influenced by clinical size (p < 0.002) and SP (p < 0.016) on univariate
      analysis. On multivariate analysis only clinical size (p < 0.002) continued to be
      a significant factor for local control. Factors on multivariate analysis that
      resulted in significant improvements in cancer-specific survival included any
      response to preoperative CTX/XRT (p < 0.017) and administration of adjuvant
      chemotherapy (p < 0.034). Any response to preoperative CTX/XRT improved distant
      metastatic-free and disease-free survival rates. Multivariate analysis confirmed
      that a response to preoperative CTX/XRT predicted for improvements in overall
      survival among patients with locally advanced rectal cancer. Patients who fail to
      respond to preoperative 5-FU based chemotherapy given concomitantly with
      radiation have higher rates of distant metastases with adjuvant 5-FU therapy.

PMID- 11319281
TI  - Long-term local control and survival after concomitant boost accelerated
      radiotherapy for locally advanced cervix cancer.
AB  - Between 1989 and 1994, a prospective clinical trial tested the safety and
      efficacy of concomitant boost accelerated superfractionated (CBASF) radiotherapy
      for patients with locally advanced cervix cancer. CBASF radiotherapy included 45
      Gy/25 fractions to the pelvis and a 14.4 Gy/9 fraction concomitant boost to the
      primary tumor, followed by brachytherapy for a total point A dose of 85 Gy to 90
      Gy. The 22 patients of International Federation of Gynecology and Obstetrics
      stages IIIA-IVA who received CBASF radiotherapy now have a median follow-up time
      of more than 8 years. The 7-year actuarial rates of local control and overall
      survival are 81% and 36%, respectively. Serious late toxicity included bowel
      injury requiring colostomy in eight patients within 2.5 years after treatment,
      but no other severe toxicity was observed after longer follow-up intervals. The
      local control and survival rates achieved with CBASF radiotherapy were higher
      than those observed within a matched contemporaneous cohort of patients treated
      with standard radiotherapy alone at the same institution (p = 0.1 for local
      control, 0.09 for survival). The encouraging trend toward improved tumor control,
      tempered by the complication rate, suggests an opportunity to apply more
      sophisticated radiotherapy techniques that might sustain the favorable effects of
      dose intensification while mitigating the normal tissue toxicity.

PMID- 11319282
TI  - Breast carcinoma treated by conservative surgery: results of postoperative
      external radiotherapy with photons only and a nonsplit supraclavicular field.
AB  - Eighty-nine breasts in 85 patients were treated by lumpectomy and then
      radiotherapy from a Co-60 source only. The supraclavicular field was nonsplit.
      Eighty percent were in their 40s, 60s, or 70s with almost equal distribution. The
      majority of cases (80%) was T1 followed by T2 (18%). Axillary dissection was not
      done in 26% of patients. The majority (84%) had infiltrating ductal carcinoma; 6%
      had carcinoma in situ only. The dose to the breast including the boost was in the
      range of 6,000 cGy to 7,000 cGy in 96%, whereas in 4% it was in the range of
      5,000 cGy. Forty-four patients (49%) with N0 did not have nodal irradiation. The
      dose to the nodes in the remaining patients ranged from 5,040 to 6,840 cGy. The
      cosmetic result was good to excellent in 99% of evaluated patients. There was
      telangiectasia in 1, arm edema in 2, no fibrosis in supraclavicular-tangential
      fields junction and no other soft-tissue or bone complications. Fifteen percent
      died; 6% had no evidence of cancer, and 9% had metastatic disease. Two had local
      recurrence, but with salvage mastectomy and systemic therapy were alive and well.
      The use of external photons only for breast irradiation and a nonsplit
      supraclavicular field yielded good results compared with alternative methods.

PMID- 11319283
TI  - Stomal recurrence in patients with T1 glottic cancer after salvage laryngectomy
      for radiotherapy failures: role of p53 overexpression and subglottic extension.
AB  - The role of p53 overexpression in the development of stomal recurrence was
      studied in patients with T1 glottic cancer who had undergone salvage laryngectomy
      after primary radiotherapy failure (first recurrence). The role of subglottic
      extension of the recurrent tumor in the development of stomal recurrence was also
      studied. One hundred fourteen patients with T1 squamous cell carcinoma of the
      glottic larynx were irradiated with curative intent. A local recurrence (first
      recurrence) developed in 23 patients (20%), and salvage laryngectomy was
      performed for 20 of these patients. No postlaryngectomy radiation therapy was
      included in the treatment of recurrences. Several risk factors thought to be
      significant in the development of stomal recurrence were analyzed in these 20
      patients. Prognostic factors analyzed include: p53 overexpression in the
      preradiation biopsy specimen, subglottic extension of the first recurrence,
      thyroid cartilage and lymph node involvement at the time of first recurrence,
      emergency tracheostomy performed before salvage laryngectomy, and the
      laryngectomy procedure performed for first recurrence. Presence of p53 protein in
      the preradiation biopsy specimen of laryngeal cancer did not show any adverse
      effect on the development of stomal recurrence. Stomal recurrence developed in
      27% of patients with positive biopsies and in 20% of patients with negative
      biopsies (p = 1.00). Subglottic extension of the first recurrence was associated
      with an increased incidence of stomal recurrence. Rates of stomal recurrence were
      6% in patients without subglottic extension and 100% in patients with subglottic
      extension (p = 0.001). All other risk factors studied showed no effect on stomal
      recurrence. In this study, p53 overexpression showed no effect on the development
      of stomal recurrence after salvage laryngectomy in patients with T1 glottic
      cancer. Conversely, subglottic extension of the recurrence was found to be
      strongly associated with stomal recurrence. All other factors analyzed showed no
      effect on stomal recurrence.

PMID- 11319284
TI  - External beam radiotherapy and intraluminal brachytherapy in advanced inoperable
      esophageal cancer: JIPMER experience.
AB  - From January 1994 to September 1998, all inoperable cases of cancer of the
      esophagus at Jawaharlal Institute of Postgraduate Medical Education and Research
      (JIPMER), Pondicherry, India were given external beam radiotherapy (EBRT) 36
      Gy/18 times by anteroposterior pair. After EBRT, those patients who could be
      intubated with 16 F Levine's tube either directly or after endoscopic dilatation
      were given intraluminal brachytherapy (ILBT) 36 Gy in 48 hours at 1 cm. Others
      were treated by EBRT by posterior oblique fields 24 Gy/12 times. Fifty-eight
      patients who received EBRT and ILBT formed the study group. Fifty percent had
      middle one third growth and except for three, all were squamous cell carcinoma
      (95%). Fifty-nine percent required postradiation endoscopic dilatation. The
      overall survival rate was 24% at the end of 1 year. In one patient,
      tracheoesophageal fistula developed 4 months after treatment. Mild-to-moderate
      acute esophagitis developed in 10% of the patients, and 2% had slight hemoptysis,
      but these were not significant enough to interrupt treatment. There was no
      treatment-related mortality. Thirty-four patients (59%) were followed up for 6
      months to 5 years (mean, 9.6 months). Three patients had follow-up of more than 3
      years with no evidence of disease. EBRT with ILBT, with intermittent esophageal
      dilatations as required, offers very good palliation in advanced inoperable
      cancer of the esophagus.

PMID- 11319285
TI  - An unusual presentation of non-Hodgkin's lymphoma in the head and neck.
AB  - The lymphomas are a group of lymphoproliferative disorders that can be divided
      histologically in the two main groups of Hodgkin's and non-Hodgkin's lymphoma.
      They sometimes present in the head and neck, and the diagnosis and management
      require a multidisciplinary approach. An unusual case is described presenting at
      an advanced stage because of patient delay in seeking medical help.

PMID- 11319286
TI  - Nonaspiration puncture biopsy for suspected thoracic cavum tumor: experience of
      2,010 clinical cases.
AB  - In our hospital from October 1980 to February 2000, 2,010 patients with suspected
      thoracic cavum cancer were diagnosed by nonaspiration puncture with multiple-hole
      type and surface trough-type biopsy needles. The positive rate of cytology or
      pathology examination for lesions in pleura, mediastinum, and lung tissue were
      88.6% (148/167), 83% (297/358), and 80.2% (1,191/1,485), respectively. The mean
      positive rate in all cases was 81.4% (1,636/2,010). Complications rates for
      pneumothorax or hemoptysis were 1.3% and 0.8%, respectively, in this group. Such
      revised puncture needles have been used by us in various organs, such as brain
      tumors, metastatic lymph nodes of head and neck cancers, malignant disease of
      breast, liver, kidney, prostate, rectum and bone, etc. The use of such
      nonaspiration puncture needles is very simple, safe, and effective; even for
      beginners with this technique, the rate of successful diagnoses is fairly high.

PMID- 11319287
TI  - High-dose epirubicin plus docetaxel at standard dose with lenograstim support as
      first-line therapy in advanced breast cancer.
AB  - On the basis of preclinical and clinical data, we designed a phase II study to
      determine the efficacy and feasibility of high-dose epirubicin plus docetaxel
      (Taxotere) with lenograstim support, as first-line therapy for patients with
      advanced breast cancer. Patients with histologic evidence of metastatic breast
      cancer, without previous chemotherapy, adequate organ functions, Eastern
      Cooperative Oncology Group performance status less than 2, and signed informed
      consent entered in the trial. Treatment consisted of premedication the day before
      the treatment day for 3 consecutive days (dexamethasone 16 mg o.r. and 5-HT3
      antagonists). On the treatment day 1, epirubicin 130 mg/m2 was administered as a
      15-minute intravenous infusion followed 1 hour later by 1-hour intravenous
      infusion of docetaxel 100 mg/m2. Cycles were repeated every 21 days, for a
      maximum of 8 cycles. Lenograstim (5 microg/kg, s.c.) was started 48 hours later
      (day 4) and was given daily for 10 consecutive days. Response evaluation was made
      after the third cycle was applied, following World Health Organization criteria.
      Responding patients received five additional cycles. Median time to progression
      and survival were calculated according to the Kaplan-Meier method. A total of 32
      patients have been included in the study. A total of 236 courses were delivered.
      A total response rate of 87.5% (95% confidence interval [CI] of 77-98) was
      obtained. There were 11 complete responses and 17 partial responses. Toxicity was
      mild, with a low incidence of undesirable effects (7 cycles, 2.9% were delayed
      from 3 to 6 days because of neutropenia). After a median follow-up time of 490
      days (range, 131-966 days), the median time to progression was 490 days (95% CI
      314-575), and the median survival was 604 days (95% CI 513-785). This epirubicin
      plus docetaxel regimen is an efficient treatment for patients with advanced
      breast cancer. The lenograstim support allows the administration of such a
      chemotherapy regimen with a modest incidence of side effects. A larger number of
      patients need to be evaluated.

PMID- 11319288
TI  - Combination chemotherapy with mitoxantrone, methotrexate, and mitomycin (MMM
      regimen) in malignant pleural mesothelioma: a phase II study.
AB  - The prognosis of malignant pleural mesothelioma is poor, with a median survival
      time from diagnosis of 7 to 17 months. At present there is no standardized
      treatment of this neoplasia. Between July 1995 and January 1999, 22 patients with
      malignant pleural mesothelioma were enrolled in our study. The characteristics of
      patients were: 16 men and 6 women; median age 61 years (range, 49-77 years);
      stage (according to Butchart): 8 patients stage I, 10 stage II, 2 stage III, and
      2 stage IV; cytologic diagnosis in 5 cases and histologic diagnosis in 17 cases.
      The treatment consisted of mitoxantrone 10 mg/m2 intravenous (IV) or intrapleural
      (IPL), methotrexate 35 mg/m2 IV, and mitomycin 7 mg/m2 IV on day 1 and repeated
      every 3 weeks, with mitomycin in alternate cycles (MMM regimen). One complete
      response (4.5%) (42 months of duration) and 6 partial responses (27.3%) (5, 5, 7,
      9, 14, and 19 months of duration) were achieved; the overall response rate (ORR)
      was 31.8% (95% CI, 12.4-51.3%); 7 patients were stable under this treatment
      (31.8%). According to the pathologic type, ORR for the only epithelial type was
      39.9% (95% CI, 15.2-64.8%). Median time to progression was 6 months (range, 1
      22). The overall median survival time was 13.5 months (range, 1-50); the median
      survival time of responders significantly differed from that of nonresponders
      (18.0 versus 8.5 months; p = 0.017). This treatment produced a considerable
      clinical benefit, with improvement of dyspnea (68.4%) and pain (33.3%); 15 of 19
      patients (78.9%) with pleural effusion at the time of diagnosis showed an
      important reduction in pleural fluid during chemotherapy. Hematologic toxicity
      was the main side effect; World Health Organization grade III to IV of
      neutropenia, anemia, and thrombocytopenia were observed in 81.8%, 13.6%, and
      22.7% of patients, respectively. From the data presented here, this regimen can
      be considered active in the treatment of malignant pleural mesothelioma.

PMID- 11319289
TI  - Measurement of serum CA 19-9 may be more valuable than CEA in prediction of
      recurrence in patients with gastric cancer.
AB  - In 35 patients with recurrent gastric cancer who had undergone curative
      gastrectomy, serum carcinoembryonic antigen (CEA) and CA 19-9 (carbohydrate
      antigen) tumor marker levels were investigated. At least one tumor marker was
      elevated in 24 (68.6%) patients. The levels of serum CA 19-9 and CEA markers were
      increased in 20 (57.1%) and 12 (34.3%) patients, respectively. This difference
      was not statistically significant. However, it may be important in terms of
      clinical practice.

PMID- 11319290
TI  - Phase II evaluation of menogaril in advanced prostate cancer: Eastern Cooperative
      Oncology Group EST P-A885.
AB  - Menogaril is a semisynthetic anthracycline that is less cardiotoxic than
      doxorubicin in a preclinical model. We conducted a phase II trial to determine
      the activity of menogaril in hormone-refractory prostate cancer. Between October
      1985 and November 1987, 32 eligible patients were enrolled and were divided into
      good- and poor-risk categories, the latter being defined by prior radiotherapy to
      less than one third of the marrow-containing skeleton. Good-risk patients
      received a starting dose of 200 mg/m2 by 60-minute IV infusion, whereas the poor
      risk patients received 160 mg/m2. Treatment was repeated every 3 weeks until
      disease progression. Menogaril caused leukopenia in 90% of patients, of whom 47%
      had grade III or IV toxicity. Thrombocytopenia was uncommon and mild, with only
      three patients (9%) experiencing grade II toxicity. Nonhematologic toxicity
      included mucositis (9%), and mild weight loss in 33% of patients. Nine patients
      (28%) had stable disease of 3 or more months' duration. There were no objective
      partial or complete responses. The median time to progression for the entire
      group was 10 weeks, and the median survival time for all patients was 24 weeks.
      Because of appreciable toxicity and limited antitumor activity, further study of
      menogaril cannot be recommended in hormone-refractory prostate cancer.

PMID- 11319291
TI  - Protracted venous infusion 5-fluorouracil with concomitant radiotherapy compared
      with bolus 5-fluorouracil for unresectable pancreatic cancer.
AB  - Radiation therapy (RT) with concurrent 5-fluorouracil (5-FU) administered by
      protracted venous infusion (PVI) replaced our prior institutional protocol of RT
      with bolus administration of 5-FU as standard therapy for unresectable pancreatic
      cancer in 1994. In this article, we compare the treatment intensity, toxicity,
      and outcome for patients with unresectable pancreatic cancer treated on these
      sequential protocols. Fifty-four patients, 27 on each protocol, with biopsy
      confirmed pancreatic cancer received chemoradiotherapy. The radiotherapy field
      included the gross tumor volume and regional lymph nodes to a dose of 45 Gy,
      followed by "boost" to the gross tumor volume to 54 Gy to 60 Gy. From 1987 to
      1994, patients received concurrent 5-FU administered by bolus injection, at a
      dose of 500 mg/m2 on days 1 to 3 and days 29 to 31 of RT. After December 1994, 5
      FU was administered by PVI (200-250 mg/m2) beginning on day 1 and continuing
      until the completion of RT. The chemotherapy treatment intensity was increased in
      the group receiving 5-FU by PVI, as evidenced by an increased average weekly and
      cumulative dose of 5-FU (p < 0.01). The radiotherapy treatment intensity was
      equivalent between the two groups. The incidence of objectively quantified
      toxicity was not statistically different between treatment groups. Overall
      survival remained poor in both treatment groups. With a median follow-up of 18
      months (range: 3-30 months) for surviving patients, the 6-month, 1-year, and 2
      year survivals for the PVI 5-FU-treated group versus the bolus 5-FU-treated group
      were 56% versus 52%, 34% versus 18%, and 22% versus 13%, respectively (p = 0.9).
      Radiotherapy with concomitant 5-FU by PVI results in a greater weekly and total
      dose of chemotherapy. The method of 5-FU administration (bolus versus PVI) did
      not change the RT treatment intensity, experienced toxicity, or overall survival.

PMID- 11319292
TI  - Detection of human papillomavirus DNA in primary and metastatic lesions of
      carcinoma of the cervix in women from Okinawa, Japan.
AB  - Of 351 patients with invasive cervical cancer treated at Ryukyu University
      Hospital, Okinawa, 293 who were tested for human papilloma virus (HPV) DNA of the
      primary cervical lesion before the initiation of treatment were considered for
      the study. The polymerase chain reaction (PCR) was performed using fresh
      specimens, immediately after sampling. In 250 of 293 patients (85.3%), HPV DNA
      was detected in cervical tumor by PCR using L1 consensus primer. The positive
      rate by histology was 89.9% in squamous cell carcinoma, 93.8% in adenosquamous
      carcinoma, and 51.4% in adenocarcinoma. The former two figures were significantly
      higher than the latter (p < 0.001 and p = 0.002). Concerning identification of
      HPV types, HPV 16 was most predominant in squamous cell carcinoma, whereas type
      18 was relatively high in adenocarcinoma. However, the type distribution of HPV
      was different to some extent from those in other countries. During treatment, 489
      nodal and other tissue samples were obtained from 113 of 250 HPV DNA-positive
      patients, and were submitted to an assay of HPV DNA. HPV DNA was amplified in all
      55 metastatic samples and also in 12 of 434 nonmetastatic tissues (2.8%). HPV
      types specified in these samples were always identical with the HPV types
      determined in their primary tumors. In 154 samples from 29 of 43 HPV DNA-negative
      patients, HPV DNA was not detected, either in 14 metastatic samples or in 140
      histologically benign samples. Cancer-free, but HPV DNA-positive nodal, liver,
      and pulmonary tissues could be interpreted to be already involved at the time of
      examination, by observing the clinical course of the disease over time.

PMID- 11319293
TI  - Phase 1 drug interaction study of suramin and warfarin in patients with prostate
      cancer.
AB  - Potential interaction between suramin and warfarin was evaluated when
      coadministered to patients with cancer. Thirteen men with advanced hormone
      refractory prostate cancer were initially stabilized with warfarin to a
      prothrombin time (PT) of 2 +/- 0.2 International Normalized Ratio (INR) during a
      lead-in period of 4 weeks. A baseline daily warfarin dose was established, and
      treatment with suramin plus hydrocortisone was then started. The effect of
      suramin on the anticoagulant activity of warfarin was assessed in each patient by
      comparing his baseline warfarin dose with average daily doses required to
      maintain the same INR level over each of the initial 6 weeks of a 12-week course
      of suramin treatment. The average daily dose of warfarin required to maintain PT
      at 2 +/- 0.2 INR decreased from a baseline value of 4.2 to between 3.4 and 4.0
      during the 6 weeks of suramin plus warfarin treatment. Despite failing to
      demonstrate equivalence applying a 90% confidence interval approach, required
      reductions in warfarin dose were clinically minor and the combination was well
      tolerated. Based on these results, the eligibility criteria for a large ongoing
      randomized study were amended to allow entry of men receiving warfarin therapy.
      This interaction study, together with experience gained in a larger trial
      setting, has confirmed that warfarin and suramin can be safely coadministered,
      provided that coagulation status is appropriately monitored.

PMID- 11319294
TI  - Shoulder and arm problems after radiotherapy for primary breast cancer.
AB  - There is little, if any, difference in disease-free or overall survival for
      patients with stage I and II breast cancer treated by either breast conservation
      therapy or mastectomy. With either treatment, there may be cosmetic and
      functional problems related to arm edema, limited shoulder motion, and shoulder
      pain. The extent to which factors such as surgery, radiotherapy, systemic
      therapy, and patient characteristics affect development of arm edema, limited
      shoulder motion, and shoulder pain is not well documented. We undertook a
      prospective study of arm edema, limited shoulder motion, and shoulder pain in
      every patient (N = 331) seen during a 6-month period for follow-up after
      radiotherapy postlumpectomy or mastectomy for primary breast cancer. Local
      treatment included lumpectomy and breast irradiation with (n = 232) or without (n
      = 97) axillary dissection. Ten other women underwent mastectomy and postoperative
      radiotherapy. Doses to each region treated were 50 Gy in 25 fractions. The
      operative area was treated with an additional 1,000 Gy in approximately 60% of
      patients. Twelve patients received axillary irradiation without axillary
      dissection, and 11 patients received supraclavicular irradiation. Chemotherapy
      with or without tamoxifen was used in 71 patients and tamoxifen alone was used in
      150 patients. One hundred ten patients did not receive any adjuvant therapy.
      Ipsilateral arm edema occurred in 20 women (6.0%), limited ipsilateral shoulder
      motion in 5 (1.5%), and ipsilateral shoulder pain in 5 (1.5%). Edema was mild
      (1+) in 15 patients and moderate (2+) in five patients. Multivariate analysis
      revealed that the risk of arm edema was significantly increased in black women (p
      = 0.005, 4/18 versus 16/313 whites) and with mastectomy (p = 0.048, 2/10 versus
      18/321 with lumpectomy). There is a low incidence of arm edema, decreased range
      of motion of the ipsilateral shoulder, and shoulder-arm pain in patients
      undergoing postlumpectomy or postmastectomy radiotherapy. The risk of arm edema
      is increased in black women and in patients after mastectomy as opposed to
      lumpectomy.

PMID- 11319295
TI  - Fractionated doses of oral etoposide in the treatment of patients with aids
      related kaposi sarcoma: a clinical and pharmacologic study to improve therapeutic
      index.
AB  - The purpose of this study was to examine the antitumor activity, toxic effects,
      and plasma pharmacokinetics of fractionated doses of oral etoposide aiming at the
      achievement of prolonged safe and active plasma drug levels in patients with AIDS
      related Kaposi sarcoma (KS). This was designed as a phase II trial in which
      consecutive patients with progressing AIDS-KS after at least 3 months of active
      antiretroviral therapy received oral etoposide at the dose of 20 mg/m2 every 8
      hours daily for 7 days every 21 days, with the study of its plasma
      pharmacokinetics. Eligible patients were 18 to 60 years old, with a
      histopathologically confirmed diagnosis of AIDS-related KS, human
      immunodeficiency virus-positive test, progressing after at least 3 months of
      active antiretroviral therapy, World Health Organization (WHO) performance status
      0 to 3, New York University staging IIA or greater, no active infection except
      oral candidiasis, normal bone marrow, liver, and renal function, and who signed
      an informed consent. Objective tumor responses were evaluated after at least one
      full treatment course according to a modified WHO criteria, and toxicity was
      evaluated weekly and graded using the National Cancer Institute-Common Toxicity
      Criteria (NCI-CTC) criteria. For the pharmacokinetic study, plasma was obtained
      from patients during the first drug administration immediately before and at
      various time points thereafter. Etoposide was measured after extraction from
      plasma by a standard high-performance liquid chromatography. Twenty-one patients
      were accrued for the study, and 18 of them met the eligibility criteria. They
      were all men, with median age of 36 years old (range: 25-50 years), median WHO
      performance status 0 (range: 0-3) median CD4+ count (cells/mm3) 67 (range: 8
      443), prior AIDS diagnosis in 10 of 18 cases, NYU staging IIA (1 patient), IIB
      (1), IIIA (7), IIIB (1), IVA (4), and IVB (4) sites of disease: mucocutaneous
      only (5), mucocutaneous/lymph nodes (5), mucocutaneous/lung (5) and
      mucocutaneous/lymph nodes/lung (2); and prior cytotoxic treatment in two
      patients. Seventy-two percent of cases presented some form of toxic effect (NCI
      CTC). Leukopenia was documented in 50% of cases, anemia occurred in 61%, whereas
      thrombocytopenia was documented in 17% of the patients. The main nonhematologic
      toxicities were nausea and vomiting in 17% of cases and alopecia in 44%. The
      overall objective response rate was 83%, with 2 complete remissions documented
      (11%). The median duration of responses was 12 weeks (range: 3-45 weeks). The
      median t1/2 of etoposide in plasma was 4.11 hours (range: 1.95-9.64), area under
      the curve was 13.51 microg/h/ml (range: 7.12-24.42), Cmax was 2.17 microg/ml
      (1.40-4.41), tmax (1.00-2.00), mean residence time 4.62 hours (range: 3.75-5.20
      hours), CIt (total clearance) 3.13 l/m2/h (range: 1.49-5.20 l/m2/h), Vd 13.08
      l/m2 (range: 6.23-19.65 l/m2), and the median etoposide plasma concentration time
      greater than 1 microg/ml was 3.69 hours (range: 1.00-6.80 hours). The use of
      fractionated oral daily doses of etoposide produced significant antitumor
      activity with manageable clinical toxicity in the individuals with AIDS-KS
      included in this trial. This more favorable therapeutic index of etoposide could
      be due to the achievement of more sustained plasma levels of the drug within safe
      but active concentrations.

PMID- 11319296
TI  - Intraarterial infusion chemotherapy and radiotherapy with or without surgery for
      patients with locally advanced or recurrent breast cancer.
AB  - We analyzed response, side effects, and local control rates of a multimodal
      treatment consisting of intraarterial infusion chemotherapy (IAIC) and
      radiotherapy with or without surgery for patients with locally advanced or
      recurred breast cancer. Thirty-three patients, clinically diagnosed as stage IIB
      in 1, IIIA in 2, IIIB in 12, IV in 18, were treated from 1991 to 1998. Twenty
      five were primary and eight were recurrent cases after surgery. IAIC started as
      initial treatment up to three times maximum. In most cases, doxorubicin 50 mg,
      cisplatin 50 mg, and mitomycin 10 mg were infused in the subclavian and/or
      internal mammary artery. After IAIC, patients in primary cases underwent radical
      mastectomy or breast conservation surgery, after radiotherapy at a total dose of
      50 Gy/25 fractions/5 weeks with a boost of 10 Gy. In recurrent cases, a full dose
      of radiotherapy was delivered. Clinical objective and complete response rates
      were 78% and 9% after IAIC. Despite a high rate of residual positive margin (67%)
      or clinically residual carcinoma, local recurrence developed only in 2 patients
      (6%) and local control rates at 5 years were calculated as 89%. Bone marrow
      suppression was frequent, and skin vesiculation (15%) and ulceration (9%) were
      experienced after IAIC. Skin ulcer (6%), brachial plexus neuropathy (3%), and
      radiation pneumonitis (3%) occurred as late toxicity. IAIC was effective as an
      induction treatment and radiotherapy played a role of local control for patients
      with locally advanced or recurrent breast cancer.

PMID- 11319297
TI  - Renal tolerance to cisplatin in patients 70 years and older.
AB  - The purpose of this study was to evaluate cisplatin nephrotoxicity in patients 70
      years and older and to identify factors influencing nephrotoxicity occurrence.
      Forty-nine (N = 49) patients older than 70 years were studied retrospectively.
      All patients received treatment with cisplatin. Variables under study were as
      follows: prechemotherapy serum creatinine levels (Crb), maximum serum creatinine
      level during treatment (Crmax), steady serum creatinine level 3 months after
      treatment completion (Crstb), as well as their corresponding creatinine clearance
      values (CrbC, CrmaxC, CrstbC) as calculated by the Cockroft and Gault formula.
      Maximum creatinine increment (Imax = Crmax - Crb), stable creatinine increment
      (Istb = Crstb - Crb) and the corresponding clearance decrements (Dmax and Dstb)
      were calculated as well. The potential relationship of the above variables to
      cisplatin dose intensity and accumulated dose as well as to different prognostic
      factors were also considered. Assessment of associated conditions was carried out
      by means of Charlson comorbidity index. The patients' mean age was 73 years
      (range: 70-79 years). There were 43 men (88%) and 6 women (12%). Mean cisplatin
      dose intensity was 27 mg/m2/wk. A total of 157 chemotherapy courses were
      administered with a mean of 3.2 per patient. Mean Crb was 1.02 mg/dl (95% CI =
      1.02-1.12), mean Crmax was 1.45 (95% CI = 1.34-1.46), and mean Crstb was 1.24
      (95% CI = 1.16-1.32). Imax was equal to 0 in 13 patients (26%) and more than 0.4
      mg/dl in 21 patients (43%). Istb was equal to 0 or negative in 22 (45%) and more
      than 0.4 in only 9 patients (18.3%). No significant relationship of serum
      creatinine levels, creatinine clearance levels, or of their increments or
      decrements to cisplatin dose intensity or accumulated dose were found. These
      levels also did not correlate with age, sex, comorbidity or Eastern Cooperative
      Oncology Group score. In 85% of patients, Crmax was reached between chemotherapy
      initiation and the third chemotherapy course, and thereafter renal function began
      to recover despite continued administration of cisplatin. Cisplatin is well
      tolerated by patients 70 years and older and dose intensity does not seem to
      influence renal function deterioration. Therefore, we failed to find reasons to
      encourage modification or limitation of cisplatin treatment in the elderly
      population.

PMID- 11319298
TI  - Surgical treatment for pancreatic metastasis from soft-tissue sarcoma: report of
      two cases.
AB  - We present two cases in which a soft-tissue sarcoma metastasized to the pancreas,
      but both patients survived as a result of repetitive surgical treatment during a
      6- to 10-year period. The first case was a 29-year-old man who had a history of
      removal of mesenchymal chondrosarcoma in the left thigh in 1986 and who underwent
      distal pancreatectomy and the enucleation of a tumor in the head of the pancreas
      because of the development of three metastatic lesions in 1989. Afterward,
      although metastases were found in other organs, they were resected each time (for
      a total of five times) and the patient has survived over 10 years. The second
      case was a 40-year-old woman who had a history of the removal of synovial sarcoma
      in the right thigh and had 6 surgical resections of local or pulmonary recurrent
      tumors. She underwent pylorus-preserving pancreaticoduodenectomy in 1993 because
      of the development of a solitary metastatic lesion in the pancreas and survived
      more than 6 years after the pancreatectomy. Our report suggests, in selected
      cases, that long-term survival from pancreatic metastasis of soft-tissue sarcoma
      is expected as a result of curative resection. However, because pancreatic
      metastasis has a potential to recur in other organs, it is necessary to take
      aggressive surgical procedures repeatedly for the treatment of recurrences to
      improve prognosis after pancreatectomy.

PMID- 11319299
TI  - Diffuse large B-cell non-Hodgkin's lymphoma presenting as a vaginal mass in a
      patient with a history of intestinal mucosa-associated lymphoid tissue (MALT)
      lymphoma.
AB  - Vaginal involvement in non-Hodgkin's lymphoma is uncommon and is often secondary
      to disseminated disease. Primary disease at this site is quite rare. We present
      here an unusual case of a patient who developed a diffuse large B-cell lymphoma
      presenting as a vaginal mass after having been treated for primary intestinal
      mucosa-associated lymphoid tissue (MALT) lymphoma 4 years earlier. Combined
      chemotherapy and radiation therapy for the intestinal MALT lymphoma produced
      complete remission that lasted for 2 years. Chemotherapy given for the diffuse
      large B-cell lymphoma with secondary vaginal involvement produced a second
      complete remission. The second remission was consolidated with high-dose
      chemotherapy and autologous bone marrow transplantation. Although the patient
      died from complications related to the transplant procedure, the disease was in
      complete remission at the time of her death. Given the rarity of primary
      intestinal MALT lymphoma and primary vaginal lymphoma, no standard treatment has
      been established. Treatment options have included chemotherapy, radiation
      therapy, or surgery, given alone or in combination.

PMID- 11319300
TI  - The American Cancer Center.

PMID- 11319301
TI  - Bilateral inflammatory breast involvement as the first site of relapse of ovarian
      carcinoma.

PMID- 11319302
TI  - Methotrexate-induced radiation recall.

PMID- 11319303
TI  - Use of corticosteroid therapy in autoimmune hepatitis resulting in the resolution
      of cirrhosis.

PMID- 11319304
TI  - Radiofrequency ablation of liver tumors.

PMID- 11319305
TI  - Office-based testing for gastric emptying: a breath away?

PMID- 11319306
TI  - Molecular testing of Helicobacter pylori-associated chronic gastritis and
      premalignant gastric lesions: clinical implications.
AB  - Helicobacter pylori-associated gastritis may progress or be complicated by peptic
      ulcer and gastric malignancy, including gastric carcinoma and mucosa-associated
      lymphoid tissue lymphoma. Predicting who develops malignancy remains a clinical
      challenge. The molecular understanding of pathways that are associated with
      progression of the normal gastric epithelium to malignancy together with classic
      histologic parameters are promising ways of tackling this problem. Ideally,
      molecular tools used for screening should be available as noninvasive tests, such
      as examination of markers detectable in blood samples, but these are not
      currently available. In contrast, molecular markers that correlate with cancer
      risk can be examined in the epithelium after endoscopic biopsy and can be of
      importance in identifying individuals at risk, especially if combined with other
      parameters of gastric cancer risk.

PMID- 11319307
TI  - Randomized control trials on chemoembolization for hepatocellular carcinoma: is
      there room for new studies?
AB  - Hepatocellular carcinoma (HCC) generally occurs in patients with cirrhosis.
      Curative options, such as liver transplantation, hepatic resection, and
      percutaneous alcohol injection, are applicable to a minority of cases. Because
      systemic chemotherapy and radiation therapy provide dismal results, transarterial
      chemoembolization (TACE) remains the sole approach to antagonizing the cancer
      growth in most patients. Although most tumors show an extensive necrosis after
      TACE, the beneficial effect on survival has not been properly substantiated, so
      that its application still remains a matter of debate. This review analyzes the
      results of randomized clinical trials on TACE. In most studies, TACE did not
      increase the survival of patients as compared with the palliative treatment.
      However, several methodologic and technical pitfalls may have adversely affected
      the results of these trials, such as inadequate patient selection and statistical
      power of the study design, a nonoptimal procedure, and treatment repetition not
      tailored to the cancer response and patient tolerance. Nonetheless, the
      literature will hardly be enriched by new trials including untreated patients
      because, wrong or right, TACE is currently considered the standard treatment of
      unresectable HCC. It seems more realistic to expect randomized studies comparing
      different techniques and time schedules of treatment, as well as TACE alone
      versus combined procedures.

PMID- 11319308
TI  - Endoscopic ultrasound-guided (neurolytic) celiac plexus block.
AB  - Celiac plexus neurolysis is an established technique for relieving pain in
      cancers of the upper abdomen. This article reviews the novel technique of
      endoscopic ultrasound (EUS)-guided neurolytic celiac plexus block. This recently
      described procedure is a therapeutic extension of curvilinear array
      endosonographic fine needle aspiration. The indications, patient preparation, and
      technical aspects of the procedure are described in detail. The potential
      complications are mentioned and the results of the published studies are
      reviewed. We believe that where the expertise is available, this procedure can be
      integrated into the diagnostic EUS of patients with inoperable upper abdominal
      malignancy. As such, this would be the safest and most cost-effective approach
      for celiac plexus neurolysis in these patients. The role of EUS-guided celiac
      plexus block in patients with chronic pancreatitis may be emerging and needs
      further study.

PMID- 11319309
TI  - Gastric emptying characteristics of a novel (13)C-octanoate-labeled muffin meal.
AB  - GOALS: Determine the gastric emptying characteristics of a novel, 350-kcal test
      meal consisting of two muffins, using scintigraphy and the 13C-octanoate breath
      test (OBT). STUDY: Healthy volunteers underwent three studies on separate days
      within a 1-week period. On day 1, we measured emptying of the 350-kcal muffin
      test meal labeled simultaneously with 99mTc sulfur colloid and 13C-octanoate. On
      day 2, reproducibility of the OBT using a single-labeled 350-kcal test meal was
      assessed. On day 3, the effect of erythromycin on the 350-kcal OBT was
      determined. RESULTS: The mean (+/-SD) half-emptying time (T1/2) as measured by
      scintigraphy was 104 +/- 24 minutes, versus 212 +/- 52 minutes by OBT. There was
      a strong correlation between T1/2 determined by scintigraphy and the breath test
      (r = 0.83). Multiple linear regression analysis identified a significant
      relationship between T1/2 determined by scintigraphy and the 90-and 180-minute
      breath samples. There was a strong correlation (r = 0.830, slope = 0.732 +/-
      0.120 [SE], intercept = 26.4 +/- 12.7) between the T1/2 obtained using the
      regression equation and the actual T1/2 obtained by scintigraphy. The mean T1/2
      (+/-SD) for replicate determinations using the OBT was 209 +/- 52 minutes,
      compared with 196 +/- 42 minutes on days 1 and 2, respectively (not significant,
      p = 0.28, paired Student t test). Treatment with erythromycin on day 3 produced a
      significant decrease in T1/2 (155 +/- 49 minutes, p = 0.002). CONCLUSIONS: The
      350-kcal muffin meal OBT provides a convenient, nonscintigraphic way of measuring
      solid-phase gastric emptying. Multiple linear regression appears promising as a
      method of analyzing OBT data and may allow for an abbreviated breath test
      protocol.

PMID- 11319310
TI  - Inability to noninvasively diagnose gastric intestinal metaplasia in Hispanics or
      reverse the lesion with Helicobacter pylori eradication.
AB  - BACKGROUND: Helicobacter pylori infection has been linked with the development of
      gastric adenocarcinoma and its precursor lesion, intestinal metaplasia (IM). The
      presence of gastric IM is not associated with symptoms, which makes
      identification of individuals with this lesion difficult. It is not clear whether
      eradication of H. pylori infection leads to reversal of gastric IM or the
      potential decrease in the risk of cancer in these patients. GOALS: The purpose of
      this pilot study was to define the prevalence of gastric IM in a population at
      high risk for gastric cancer (Southwestern Hispanics), examine the ability of
      noninvasive testing to identify individuals with the lesion, and determine
      whether eradication of H. pylori infection reverses gastric IM in this
      population. STUDY: Subjects from the Tucson metropolitan area were recruited, and
      baseline data, including the presence of upper gastrointestinal (UGI) symptoms,
      urinary sodium, and serum pepsinogen levels, were obtained. Upper endoscopy was
      performed and six gastric biopsies from specific anatomic sites were obtained,
      followed by methylene blue staining with targeted biopsies from blue-stained
      mucosa. Biopsies were evaluated for the presence of H. pylori infection and
      gastric IM. A subset of patients with gastric IM were treated to eradicate H.
      pylori infection. Follow-up exams with methylene blue staining, including
      biopsies for histology and rapid urease testing, were performed for up to 48
      months. RESULTS: There were 84 subjects with a mean age of 53.0 years; 24 (29%)
      had gastric IM and 65 (77%) had H. pylori. There was no significant association
      between gastric IM and age, gender, UGI symptoms, H. pylori, or urine sodium.
      There was an association identified between gastric IM and a decreased pepsinogen
      I:II ratio (p = 0.03). Of the 11 individuals with gastric IM treated for H.
      pylori infection, 9 had successful therapy and underwent at least 2 follow-up
      examinations. The mean length of follow-up was 3.3 years. Eight of the nine (89%)
      had gastric IM identified histologically at the final endoscopic exam.
      CONCLUSIONS: H. pylori infection and gastric IM are frequent findings in
      Southwestern Hispanics, a high-risk population for gastric cancer. Noninvasive
      testing is not clinically useful in distinguishing individuals within this group
      who harbor gastric IM. Although eradication of H. pylori infection may lead to a
      decrease in the amount of gastric IM in some individuals, the lesion may be
      detected in the majority of individuals after more than 3 years of follow-up.
      These data suggest that therapy for H. pylori may not eliminate the risk of
      gastric cancer once IM has developed.

PMID- 11319311
TI  - Plasma and gastric tissue selenium levels in patients with Helicobacter pylori
      infection.
AB  - GOALS: We investigated plasma and gastric mucosal selenium levels in patients
      with Helicobacter pylori (HP)-associated histopathologic findings in their
      gastric antral mucosa. STUDY: Before and after a successful HP eradication
      therapy, we quantitated the plasma and antral selenium levels in patients with HP
      associated chronic antral gastritis using atomic absorption flame emission
      spectrometry. The same measurements were done in patients with dyspeptic
      complaints who had normal antral histology and negative urease test. RESULTS:
      Thirty-four patients were studied, of whom 24 had HP-associated chronic antral
      gastritis confirmed by histology and positive urease test; the control group
      included 10 healthy patients. There was no difference between the groups with
      regard to age, gender, and number of smokers. All patients with HP infection were
      diagnosed with diffuse antral gastritis. Histopathology showed that 11 (49%) had
      some degree of atrophy. Of the 11 patients, 7 were classified as having chronic
      atrophic gastritis (CAG) without intestinal metaplasia (IM), 4 had IM, and none
      had dysplasia. The plasma concentrations of selenium were found to be very
      similar in controls and HP-infected subjects (68.0 +/- 25.97 microg/L and 71 +/-
      32.9 microg/L, respectively; p > 0.05). The antral biopsy samples of the patients
      with HP-associated gastritis contained significantly higher levels of tissue
      selenium than the controls (20.17 +/- 19.74 microg/g and 2.83 +/- 1.42 microg/g,
      respectively; p < 0.05). Also, it was shown that antral tissue selenium levels
      decrease after successful HP eradication therapy (20.17 +/- 19.4 microg/g and 7.4
      +/- 4.56 microg/g, respectively; t < 0.05). The patients with HP gastritis were
      assigned to mild, moderate, and severe gastritis groups, according to the
      histopathologic degree of inflammation present. The antral gastric selenium
      levels were significantly higher in patients with moderate and severe HP
      gastritis (21.13 +/- 22.5 microg/g and 22.81 +/- 17.35 microg/g, respectively)
      than in patients with mild gastric inflammation (9.53 +/- 10.3 microg/g; p <
      0.05). The selenium concentrations in the biopsies of patients with CAG were
      significantly lower than in those with HP gastritis who did not have CAG (9.45 +/
      6.44 microg/g vs. 19.13 +/- 22.48 microg/g, respectively; p < 0.05).
      CONCLUSIONS: Selenium accumulates in gastric tissue when it is needed, as is the
      case in HP-related antral inflammation. This reactive increase in gastric mucosal
      selenium seems to disappear in the presence of precancerous gastric lesions in
      the setting of HP-associated gastritis.

PMID- 11319312
TI  - Abscesses in Crohn's disease: outcome of medical versus surgical treatment.
AB  - GOALS: To compare the long-term outcome of medical, percutaneous, and surgical
      treatment of abdominal and pelvic abscesses complicating Crohn's disease. STUDY:
      All patients with Crohn's disease and an abdominal abscess treated at one
      institution during a 10-year period were retrospectively identified. We reviewed
      hospital and outpatient records and contacted patients for telephone interviews.
      Outcome measures included abscess recurrence, subsequent surgery for Crohn's
      disease, and medications used at the time of most recent follow-up. RESULTS:
      Fifty-one subjects were identified, with a mean follow-up of 3.75 years. Fewer
      patients developed recurrent abscesses after initial surgical drainage and bowel
      resection (12%) than patients treated with medical therapy only or percutaneous
      drainage (56%) (p = 0.016). One half of the patients treated nonoperatively
      ultimately required surgery, whereas only 12% of those treated with initial
      surgery required reoperation during the follow-up period (p = 0.010). Most
      failures of nonoperative therapy occurred within 3 months. Medication use was
      similar between the treatment groups at the time of most recent follow-up.
      CONCLUSIONS: In this series, surgical management of abscesses in Crohn's disease
      was more effective than medical treatment or percutaneous drainage for prevention
      of abscess recurrence. However, nonoperative therapy prevented subsequent surgery
      in half of the patients and may be a reasonable treatment option for some
      patients.

PMID- 11319313
TI  - Assessment of fatigue and psychologic disturbances in patients with hepatitis C
      virus infection.
AB  - BACKGROUND: It is a common clinical impression that fatigue is a frequent, and
      often debilitating, symptom in patients with chronic hepatitis C virus (HCV)
      infection. However, despite its obvious clinical importance, several aspects of
      fatigue, including its relationship with the underlying liver disease and the
      presence of psychologic disturbances, have not been well examined. GOALS: The
      current study was carried out to assess these issues. STUDY: A total of 149
      subjects were included in the study and were assigned to one of the following
      study groups: healthy controls (31), chronic HCV infection (24), combined HCV
      infection and chronic alcohol abuse (32), alcoholic liver disease (22), and
      chronic non-liver diseases (40). All subjects were administered investigator
      assisted questionnaires designed to analyze the presence and severity of fatigue
      and psychologic abnormalities. RESULTS: The mean (+/-SD) fatigue scores in
      patients with chronic HCV infection (140 +/- 22.9; p = 0.002), alcoholic liver
      disease (127 +/- 31.4; p < 0.001), mixed (HCV/alcoholic) liver disease (131 +/-
      29.0; p < 0.001), and chronic non-liver diseases (128 +/- 35.9; p = 0.004) were
      significantly greater compared to with healthy subjects (101 +/- 31.8). The total
      fatigue scores were higher in HCV-infected subjects compared with the other
      patient groups, but the differences failed to reach statistical significance.
      Moreover, the fatigue experienced by patients with HCV did not improve with rest
      as effectively as in the other study groups. All patient groups had higher scores
      for psychologic disturbances compared with healthy subjects. CONCLUSIONS: The
      current study shows that fatigue and psychologic disturbances occur frequently in
      chronic diseases. The fatigue experienced by patients with HCV infection is more
      severe and intransigent and responds poorly to relieving factors. Moreover,
      patients with HCV infection are more depressed and harbor greater feelings of
      anger and hostility compared with those with non-liver chronic diseases. These
      observations are important because proper management of the psychologic symptoms
      may have a favorable impact on the quality of life of patients with HCV
      infection.

PMID- 11319314
TI  - Percutaneous radio-frequency ablation therapy using a clustered electrode for
      malignant liver tumors.
AB  - GOALS: To examine the safety and effectiveness of percutaneous radio-frequency
      ablation therapy (PRAT) for malignant liver tumors, using a needle with cluster
      radio-frequency (RF) electrodes. STUDY: The subjects were 13 patients with
      solitary malignant liver tumors: 10 had hepatocellular carcinoma and 3 had
      metastatic liver tumors. One session of PRAT with cluster RF electrodes was
      performed until roll-off occurred two times. Dynamic computed tomography (CT) and
      fine needle tumor biopsy under ultrasonographic guidance were conducted to assess
      the therapeutic efficacy. Aspartate aminotransferase, alanine aminotransferase,
      lactic dehydrogenase, and total bilirubin were evaluated before and 1, 3, and 7
      days after PRAT. RESULTS: There were no serious complications. Aspartate
      aminotransferase, alanine aminotransferase, and lactic dehydrogenase levels
      peaked 1 day after PRAT and decreased thereafter. No icterus occurred. Of the 13
      tumors, 12 showed complete necrosis on dynamic CT; however, one of them showed
      histologically incomplete necrosis in the tumor biopsy. In both of the
      ineffective cases, the tumors were located near relatively large vessels. There
      was no recurrence in the liver in all cases of PRAT that were effective
      (observation periods: 6--14 months; mean, 10 months). CONCLUSIONS: Percutaneous
      radio-frequency ablation therapy using a clustered electrode is a safe and
      effective treatment of malignant liver tumors, if the tumor is not located near
      the large vessels.

PMID- 11319315
TI  - Ischemic bile duct injury as a serious complication after transarterial
      chemoembolization in patients with hepatocellular carcinoma.
AB  - BACKGROUND: Bile duct injuries after transarterial chemoembolization (TACE) have
      been reported; however, the exact pathogenic mechanisms and clinical implications
      of the injuries remain to be clarified. STUDY: A total of 950 consecutive
      patients with hepatocellular carcinoma (HCC) were studied. Among them, 807 were
      treated with TACE and the remaining 143 were treated with transarterial
      chemoinfusion (TACI) of cisplatin. RESULTS: None of 143 patients with HCC treated
      with TACI were found to have any radiographic evidence of biliary injury. In
      contrast, of the 807 patients treated with TACE, 17 (2%) developed biliary
      complications. Of all complications, 12 (71%) were subcapsular bilomas; 3 (17%),
      focal strictures of the common hepatic duct or common bile duct; and 2 (12%),
      diffuse mild dilatation of the intrahepatic bile ducts. Interestingly, 2 of the
      12 bilomas were found in the lobe that was not embolized with gelatin sponge
      particles. The median numbers of TACE tended to be greater in the patients with
      focal stricture than in those with bilomas (6.0 vs. 2.5; p = 0.08). All 3
      patients with focal strictures and 4 of the 12 patients with bilomas had
      associated serious bacterial infections at presentation. CONCLUSIONS: Bilomas
      seem to be caused by iodized oil rather than gelatin sponge particles; focal
      strictures of large bile ducts seem to be caused by gelatin sponge particles. We
      suggest that adjustments in the amounts of iodized oil or gelatin sponge
      particles and in the sites of embolization may reduce ischemic biliary injuries
      after TACE.

PMID- 11319316
TI  - Resolution of cirrhosis in autoimmune hepatitis with corticosteroid therapy.
AB  - Successful therapy for liver diseases, including autoimmune hepatitis, primary
      biliary cirrhosis, and hepatitis C, has been associated with a reduction in
      hepatic fibrosis. Recently, a study of needle liver biopsy specimens documented
      resolution of cirrhosis in a small group of patients with autoimmune hepatitis
      who responded to corticosteroid therapy. We describe a woman with autoimmune
      hepatitis who had cirrhosis on a wedge biopsy of the liver in 1985 and who
      attained a biochemical response with immunosuppressive therapy. A repeat wedge
      liver biopsy performed 14 years later was normal, providing unequivocal evidence
      that cirrhosis can reverse completely in autoimmune hepatitis.

PMID- 11319318
TI  - Progression of collagenous colitis to ulcerative colitis.
AB  - Collagenous colitis is a form of microscopic colitis that results in chronic
      watery diarrhea. The disorder predominantly affects middle-aged women, and its
      course tends to be benign. It is not thought to be a precursor of overt
      inflammatory bowel disease; however, apparent progression to ulcerative colitis
      has been reported on one previous occasion. We describe two further patients with
      symptoms and histologic features of collagenous colitis who subsequently
      developed ulcerative colitis. The first patient developed ulcerative colitis 13
      months after diagnosis of collagenous colitis, although she gave a 23-year
      history of profuse watery diarrhea, which had not been adequately investigated.
      In the second patient, collagenous colitis was diagnosed soon after the onset of
      watery diarrhea, and 12 months later, progression to ulcerative colitis was
      documented. Both patients tested positive for perinuclear antineutrophil
      cytoplasmic antibody after they developed ulcerative colitis; the first patient
      was initially negative. In conclusion, these two cases, in addition to the one
      other in the literature, suggest that collagenous colitis and ulcerative colitis
      may represent extremes in the spectrum of inflammatory bowel disease and that
      collagenous colitis may evolve to ulcerative colitis. Therefore, progression to
      ulcerative colitis should be considered in any patient with known collagenous
      colitis whenever bloody diarrhea occurs, or if red cells, as well as white cells,
      are noted on stool microscopy.

PMID- 11319317
TI  - Hepatic epithelioid hemangioendothelioma.
AB  - Epithelioid hemangioendothelioma (EHE) is a rare neoplasm of vascular origin with
      unpredictable malignant potential. We describe two patients with primary EHE of
      the liver and review 34 cases previously published in Japan and compare them with
      those in Western countries. The clinical aspects of EHE and relevant treatment
      results in Japanese patients were similar to those found in Western countries,
      the exception being the matter of difference in incidence between genders.
      Although this tumor type has been reported to be more frequent among women, there
      was no significant difference in incidence between men and women. Hepatic EHE
      generally behaves as a low-grade malignant tumor with a slow progression
      phenotype; however, this disease seems to be resistant to chemotherapy and to be
      lethal in some cases. Surgical resection or liver transplantation is recommended
      after rapid diagnosis by radiologic examination and histologic findings,
      including positive staining of tumor cells for factor VIII-related antigen.

PMID- 11319319
TI  - Prostate cancer metastasizing to the small bowel.
AB  - Although prostate cancer is one of the most commonly encountered malignancies in
      clinical practice, it is very unusual for prostate cancer to metastasize to the
      small bowel. Our search of the literature found no such cases published from 1966
      to the present. We report the case of a 69-year-old man who presented for
      evaluation of anasarca and anorexia. He had a history of prostate cancer
      diagnosed 9 years before and had undergone a radical prostatectomy with
      subsequent radiotherapy for positive tumor margins. He developed anasarca 2 years
      before presentation to us. His serum albumin ranged between 1.5 and 2.5 g/dL.
      Upper endoscopy was performed for possible protein-losing enteropathy and the
      appearance of gastric and duodenal mucosa was found to be normal. Random small
      bowel biopsies revealed submucosal infiltrating adenocarcinoma with positive
      prostate-specific antigen stains consistent with the diagnosis of prostate cancer
      metastatic to the small bowel. This is a rare presentation of metastatic prostate
      cancer. Even though prostate cancer is the most commonly diagnosed cancer in
      American men, antemortem diagnosis of small bowel metastasis has not been
      reported. In patients with unexplained anasarca, especially with a history of
      malignancy, an upper endoscopy with small bowel biopsy may be useful in
      establishing the diagnosis.

PMID- 11319320
TI  - Microcytic adenoma coexistent with low-grade malignant islet cell tumor of the
      pancreas.
AB  - We report a case of microcystic (glycogen-rich) adenoma of the whole pancreas
      with coexistent pancreatic low-grade malignant islet cell tumor in a 29-year-old
      woman. She complained of nausea, vomiting, and growing abdominal mass. Abdominal
      computed tomography showed multiple cysts in the whole pancreas and a calcified
      solid mass in the pancreatic head. A Whipple's operation and total pancreatectomy
      with splenectomy was performed to treat pancreatic cystic neoplasm. The pancreas
      was entirely replaced by variable-sized, multilocular cysts, which were lined by
      a flattened-to-cuboidal glycogen-rich epithelium. Furthermore, in the head of the
      pancreas, a focal yellowish solid mass showed a positive reaction for
      chromogranin A and neuron-specific enolase. Careful examination of the pancreas
      is warranted in cases of microcystic adenoma to rule out a possible coexistent
      pancreatic malignancy.

PMID- 11319321
TI  - Pancreatic cancer presenting as bleeding gastric varices.
AB  - Given the extremely poor prognosis of pancreatic adenocarcinoma, early diagnosis
      is crucial; however, clinical signs and symptoms of the disease are neither
      sensitive nor specific. In the two cases described, previously undiagnosed
      pancreatic cancers initially presented with upper gastrointestinal tract
      hemorrhage. Endoscopic surveys to identify the origin of the bleeding revealed
      gastric varices secondarily attributed to splenic vein thrombosis. Upon further
      investigation, the splenic vein occlusions were found to be caused by pancreatic
      tumors. A review of the incidence, pathogenesis, diagnostic modalities, and
      implications of splenic vein occlusion is included.

PMID- 11319322
TI  - A giant Brunner's gland adenoma presenting as gastrointestinal hemorrhage.
AB  - Brunner's gland adenomas are rare tumors of the duodenum that are usually small
      in size. Only a few cases of tumors more than 4 to 5 cm in size are reported in
      the literature. Although the majority of patients are asymptomatic, hemorrhage
      and obstruction are the most clinically significant manifestations. We report a
      case of Brunner's gland adenoma in which the patient presented with major
      gastrointestinal bleeding. Endoscopic, radiologic, and endosonographic
      appearances are illustrated.

PMID- 11319323
TI  - Anaerobic bacteremia and necrotizing fasciitis in a patient with Crohn's disease.
AB  - Crohn's disease is a chronic, granulomatous disease that affects the gut that is
      frequently treated with immunosuppressive therapy. Infectious complications are
      common and are usually related to the transmural nature of the inflammation,
      frequently manifesting as abscesses or perianal sepsis. Necrotizing fasciitis has
      not been reported in Crohn's disease. A case of a fatal necrotizing fasciitis in
      a patient with Crohn's disease after gut biopsies and corticosteroid therapy is
      reported.

PMID- 11319324
TI  - Peritonitis caused by a ruptured infected mesenteric cyst.
AB  - Perforation of a mesenteric cyst is a very rare complication of a very unusual
      lesion. Acute presentation is the rule in half of all affected children.
      Ultrasonography and computed tomography are the best preoperative diagnostic
      tools. The treatment of choice is an urgent laparotomy and complete cyst removal.
      Results are good in cases that are operated on in a timely manner.

PMID- 11319325
TI  - Familial cluster of fulminant hepatitis A infection.
AB  - Hepatitis A virus is a common cause of a self-limited liver disease. Fulminant
      hepatitis is a rare complication of acute hepatitis A infection. We report a
      small epidemic of three consecutive fulminant hepatitis A infections in three
      previously healthy siblings. This is the first report of a cluster of fulminant
      hepatitis A.

PMID- 11319326
TI  - Recurrent, progressive giant cell hepatitis in two consecutive liver allografts
      in a middle-aged woman.
AB  - In this report, we present a 41-year-old woman who developed rapidly progressive
      "giant cell hepatitis" that lead to end-stage liver disease. She underwent a
      successful liver transplantation in 1989. However, the giant cell hepatitis
      recurred in the allograft, resulting in cirrhosis within 4 years. She underwent a
      second liver transplantation in 1993. After 2 years of a relatively stable
      course, she again developed cirrhosis and was awaiting liver transplantation at
      the time of this report. The histopathologic features in the two allografts were
      identical to her original disease. Despite extensive investigations, no etiology
      for her liver disease could be found.

PMID- 11319327
TI  - An unexpected cause of hemobilia.

PMID- 11319329
TI  - Stop abusing "dyspepsia".

PMID- 11319328
TI  - True heartburn: a case of gastropericardial fistula.

PMID- 11319330
TI  - Fibroadenoma of the gall bladder.

PMID- 11319331
TI  - Endoscopic retrograde cholangiopancreatography appearances of early primary
      sclerosing cholangitis.

PMID- 11319332
TI  - Acute viral hepatitis with severe hyperbilirubinemia and massive hemolysis in
      glucose-6-phosphate dehydrogenase deficiency.

PMID- 11319333
TI  - Chicken bone in the common bile duct.

PMID- 11319334
TI  - Hyperamylasemia associated with hepatocellular carcinoma.

PMID- 11319356
TI  - [Erysipelas. Clinicopathological classification and terminology].
AB  - Erysipelas and necrotizing fasciitis are the words used to qualify 2 well-defined
      aspects of acute microbial dermohypodermal infection. According to the literature
      a third word, "cellulitis" is used to describe a large variety of inflammatory
      conditions of soft tissues, either infectious or not. The authors who advocate
      using this word consider either that an infectious cellulitis is a clinical
      variant differing from erysipelas or fasciitis, or that it describes the whole
      spectrum of acute microbial infections of soft tissues, including these 2
      entities. This term, whatever its meaning, has no anatomical or histopathological
      validation. It should be definitively deleted and replaced by "dermohypodermal
      infection".

PMID- 11319357
TI  - [Descriptive epidemiology and knowledge of erysipelas risk factors].
AB  - Few epidemiological data related to erysipelas or cellulitis is available in the
      literature. Descriptive data, such as incidence, has mainly been assessed in
      hospital settings, and exceptionally in the general population. In the only case
      control study available, main risk factors for erysipelas of the leg were
      lymphoedema and the site of entry. Leg edema, venous insufficiency, and
      overweight were associated to erysipelas to a lesser extent. Given its high
      attributable risk, secondary prevention strategies targeted at toe-web intertrigo
      should be evaluated. Risk factors for severity are difficult to assess if they
      are transient - such as NSAIDs intake. A study on prognostic factors is needed
      before intervention strategies are tested in appropriate groups of patients.

PMID- 11319358
TI  - [Erysipelas: microbiological and pathogenic data].
AB  - Streptococcus pyogenes is considered as the primary cause of erysipelas and the
      virulence factors of this species are reviewed. The role of Staphylococcus aureus
      alone or associated with Streptococcus pyogenes remains unclear. Other etiologies
      are infrequent. Several techniques were used to detect bacteria (direct
      examination, culture, antigen or genome assay) in local samples (needle
      aspiration, swab.), in others sites (throat, blood cultures), or specific
      antibodies. The performance of the various diagnosis methods is evaluated.
      Despite the combination of 2 or more methods, the etiology remains unknown in
      almost 20 p. 100 of the cases.

PMID- 11319359
TI  - [Diagnostic criteria for erysipelas].
AB  - Diagnosis of erysipelas is based upon the association of an acute inflammatory
      plaque with fever, lymphagiitis, adenopathy and hyperleukocytosis. These
      associated symptoms are variable (20-70 p. 100 of cases). Bacteriology is not
      helpful for the diagnosis of erysipelas because of a low sensitivity (hemoculture
      5 p. 100, standard examinations 5-41 p. 100), or delayed positivity (serology).
      Moreover cutaneous bacteriology is difficult to assess when other bacteria than
      streptococci are isolated. Erysipelas have to be distinguished from non
      necrotizing cellulitis by peculiar clinical features (such as erysipeloid, facial
      staphylococcal infection, Pasteurella, Haemophilus influenzae) and from
      necrotizing fasciitis. Some non-infectious diseases may mimic erysipelas such as
      venous thrombosis, familial Mediterranean fever, prosthesis intolerance, and
      compartment syndrome. Because the diagnostic value of clinical symptoms is not
      known and no diagnostic gold standard has been established, it is impossible to
      be sure that non-streptococcal erysipelas (especially staphylococcal) really
      exists. Thus, the first line treatment for all erysipelas must be an
      antistreptococcal antibiotic. Before prescribing a treatment, hemoculture and
      blood cell count could be useful. If antistreptococcal antibiotherapy is
      inefficient, all the differential diagnoses must be reviewed.

PMID- 11319360
TI  - [A prospective study on erysipelas and infectious cellulitis: how are they dealt
      within hospital?].
AB  - 771 cases of erysipelas and 52 cases of infectious cellulitis were collected over
      3 months in a prospective study carried out in French hospitals. The mean age was
      62.7 +/- 19.3 years for the erysipelas patients and 69.7 +/- 16 years for the
      cellulitis patients. Sex-ratios were respectively 0.92 and 2.7. The infection was
      mainly localized in the lower limbs in both categories (90.9 p. 100 and 71 p.
      100); the upper limbs and the face were more often involved in cellulitis than in
      erysipelas (13 p. 100 versus 5.2 p. 100 and 10 p. 100 versus 2.5 p. 100).
      Penicillin G was the initial antimicrobial treatment in 45 p. 100 of the
      erysipelas cases, whereas amoxicillin-clavulanic acid was used in 32.7 p. 100 of
      the cellulitis cases. Other antibiotics used were pristinamycin,
      antistaphylococcal penicillin, and amoxicillin. Combinations of antibiotics were
      used to treat 50 p. 100 of the cellulitis cases but only 11 p. 100 of the
      erysipelas cases. Anticoagulants were used in 67.4 p. 100 of the erysipelas cases
      and in 59.7 p. 100 of the cellulitis cases. Surgery was performed in 52 p. 100 of
      the cellulitis cases, and hyperbaric oxygen in 4.2 p. 100. The outcome was quite
      different for the 2 diseases: cure rate without complications reached 86.6 p. 100
      for erysipelas, and only 48.1 p. 100 for cellulitis; death rates reached
      respectively 0.77 p. 100 and 5.7 p. 100, median length of hospitalization 8 days
      and 21 days, and median length of antibiotic treatment 15 days and 21 days.

PMID- 11319361
TI  - [Dealing with bacterial hypodermal infection in general practice: an inquiry and
      a prospective study].
AB  - OBJECTIVE: The author had for aim to collect data on how general practitioners
      deal with bacterial hypodermal inflammation. MATERIAL AND METHODS: An enquiry on
      practice and a prospective study were carried out over 3 months. RESULTS: The
      mean number of cases reached 0.54 per physician over the 3-month period, for a
      total of 103 cases of bacterial hypodermal infection. The patients'mean age was
      slightly superior to 60 years, with a high female predominance and a preferential
      site of infection located in the lower limbs (89.6 p. 100 of the cases). 20 p.
      100 of the patients were immediately sent to hospital, mainly because of the
      importance of local and/or general symptoms, and of the underlying conditions. In
      home care, antibiotic therapy was almost always oral and consisted in courses of
      group A penicillin or pristinamycin in over half of the cases, for a mean
      duration of 12.4 days for erysipelas, and 9.1 days for cases classified as "other
      type of bacterial hypodermal infection". An anticoagulant treatment was
      associated in close to 30 p. 100 of the cases, and anti-inflammatory or
      corticoids agents were prescribed in 17.9 p. 100 of the cases. The cure rate
      among home care patients reached 89.3 p. 100 and only 3 patients were
      hospitalized after the initial treatment; these 3 patients had all been given non
      steroidal anti-inflammatory agents.

PMID- 11319362
TI  - [Which treatment for erysipelas? Antibiotic treatment: drugs and methods of
      administering].
AB  - Erysipelas is an acute, bacterial cellulitis involving the derma and hypoderma,
      without necrosis, usually due to Streptococcus pyogenes. Penicilline remains the
      'gold standard' treatment. However, others drugs, given their pharmacodynamic
      properties, may have an excellent indication here. Reccurence is the main
      evolutive risk.

PMID- 11319363
TI  - [Should NSAID/corticoids be considered when treating erysipelas?].
AB  - Using non-steroidal anti-inflammatory drugs (NSAID) in association with a
      suitable antibiotherapy in the treatment of erysipelas, is still being largely
      discussed in medical publications. When compared to other fields of medicine,
      here their use might be justified by their ability to reduce local inflammation
      processes, to relieve patients more quickly, and to prevent potential sequels due
      to an inflammatory process. Numerous reports have suggested an association
      between the use of NSAID and the progression of an invasive streptococcal
      infection, particularly necrotizing fasciitis. The exact mechanism is still
      unclear. No controlled survey (NSAID versus placebo) checking the efficiency and
      the safety of these treatments is currently available. Only one comparative study
      showed a gain of one single day for prednisolone The prednisolone-treated
      patients had a shorter median length of hospital stay (5 days vs. 6) than the
      placebo-treated ones. The median treatment time with intravenous antibiotics, in
      the placebo group, was 1 day longer than in the prednisolone group. The
      occurrence of side effects was not higher in the prednisolone group. If this
      currently available data is not sufficient to establish a relationship between
      severe infectious complications and the use of NSAID, one should be cautious when
      using them to treat erysipelas, since their efficiency has not been positively
      proved.

PMID- 11319364
TI  - [Is anticoagulant therapy useful when treating erysipelas?].
AB  - INTRODUCTION: Low or high dosage heparin adjuvant therapy for Erysipelas (E) has
      become frequent, especially in France. MATERIAL AND METHODS: Publications on
      erysipelas complications were reviewed, and 2 studies were found in which the
      detection of deep venous thrombosis (DVT) was systematically performed: Mahe A
      (6DVT/40E), and Perrot JL (4DVP/155E). We calculated the relative incidence (CRI)
      at 4.9 p. 100, for all studies systematically detecting the DVT (whether
      symptomatic or not). The other studies reported clinical DVT. CRI was at 0.7 p.
      100 without heparin adjuvant therapy. CRI was at 0, not statistically
      significant, with low or high dosage heparin adjuvant therapy. The most frequent
      complications for heparin treatment were: thrombocytopenia (5.7 and 0.9 p. 100
      respectively with standard and low weight heparin), and hemorrhage (less than 3
      p. 100 for DVT treatment). DISCUSSION: The risk of DVT associated with E is
      inferior to 10 p. 100 (the level of risk for DVT is small according to consensus
      conferences on thromboembolism). The incidence of asymptomatic DVT is superior to
      that of symptomatic DVT. But we do not know if asymptomatic DVT is equivalent to
      symptomatic DVT. Consensus conferences on thromboembolism do not recommend the
      preventive administration of heparin to bedfast patients with a low risk of DVT.
      CONCLUSION: There is no indication of adjuvant anticoagulant therapy for
      erysipelas. There is no indication for systematic prophylactic anticoagulant
      therapy for erysipelas. Prophylactic anticoagulant therapy is used depending on
      other risk factors of DVT. Wearing stockings may be another indication for
      patients.

PMID- 11319365
TI  - [Erysipelas: evolution under treatment, complications].
AB  - OBJECTIVE: The authors studied the evolution and the complications of lower limb
      erysipelas under antibiotherapy. METHOD: The following parameters were studied in
      literature over the last 20 years (keyword=erysipelas): percentage of favorable
      course, delay for cure, local or systemic complications, prognostic factors, and
      mortality. RESULTS: Data was only available in series of hospitalized patients.
      The lower limbs were the exclusive or the most frequently involved areas. Under
      systemic antibiotherapy, the overall efficacy rates reached 76-84 p. 100, with
      apyrexia within 24 to 48 h, and regression of local symptoms within 4 to 6 days.
      The median hospital stay was 10-13 days. A longer hospital stay was observed for:
      older patients, associated diseases, longer duration of illness prior to
      admission, and presence of a leg ulcer. Complications were observed: abscess or
      superficial necrosis (3-12 p. 100), deep thrombophlebitis in 1.4 p. 100 of
      retrospective studies vs. 2.6-15 p. 100 in prospective series. Mortality was low
      (0.5 p. 100) due to systemic complications more than to the severity of local
      symptoms. Relapse was frequent (15-25 p. 100). DISCUSSION: The unavailability of
      data concerning outpatients limits the formulation of valid conclusions.
      Nevertheless the medical course was favorable (80 p. 100) with apyrexia within 2
      days, and absence of local symptoms within 4 to 6 days. Mortality or longer
      duration of hospital stay was linked to age or to associated diseases. The risk
      of deep thrombophlebitis was rare in absence of predisposing factors. Systematic
      prevention should be suggested and care given to local predisposing factors
      responsible for frequent recurrent forms.

PMID- 11319366
TI  - [Primary and secondary hospitalization criteria].
AB  - The reference therapy for erysipelas is penicillin G given intravenously. Since
      I.V. injections are difficult to perform at home, hospitalization would seem
      mandatory. However, many cases of erysipelas are actually treated at home (cf.
      results of the 2 surveys concerning general practice). The lack of studies on non
      hospitalized erysipelas patients makes it difficult to answer the following
      question: "What are the criteria for primary and secondary hospitalization?" The
      literature suggests, mostly indirectly, that the reasons of primary
      hospitalization are: the severity of general (fever, impairment of general
      condition, confusion) or local (blisters, purpura, skin necrosis, extent of the
      cellulitis, facial involvement) signs and symptoms, old age, associated diseases
      (diabetes, alcoholism, obesity, cardiovascular disease), the practical modalities
      of the treatment (penicillin given intravenously, bed rest), or the necessity to
      eliminate deep venous thrombosis. The reasons for secondary hospitalization are
      above all the (true or suspected) failure of oral antibiotherapy at home, or the
      occurrence of local complications. True criteria of primary or secondary
      hospitalization remain to be defined by adequate prospective studies performed in
      both in and outpatients. They will depend of the emerging possibilities of
      successfully treating erysipelas by oral antibiotics.

PMID- 11319367
TI  - [Primary and secondary prevention for erysipelas].
AB  - Erysipelas is a bacterial infection of the deepest skin layer. Predisposing
      factors are systemic and/or local. Main systemic factors are alcoholism, diabetes
      and immunodeficiency. The main local factors are an Athlete's foot (tineapedis),
      venous or lymphatic stasis, prosthetic surgery of the knee, and a past history of
      saphenous phlebectomy, lymphadenectomy, or irradiation. Such predisposing factors
      account for the predominance of erysipelas in the lower limbs and for the
      frequency of recurrence. The prevention of recurrence is stressed by all authors,
      and would associate correct treatment of the disease, treatment of venous and
      lymphatic stasis and/or wounds. A preventive antibiotic treatment should be
      proposed to patients with multiple predisposing factors and frequent recurrence,
      by using prolonged therapy with Macrolides or Penicillin. Primary prevention
      could concern local and/or systemic predisposing factors; however its efficacy
      and necessity has yet to be demonstrated. The usefulness of nosopharyngeal
      streptococcal carriage eradication and/or vaccination has not demonstrated
      either.

PMID- 11319368
TI  - [Necrotizing fasciitis. Clinical criteria and risk factors].
AB  - Necrotizing cellulitis and fasciitis may be difficult to recognize. When skin
      necrosis is not obvious, the diagnosis must be suspected if there are signs of
      severe sepsis (accelerated heart or respiratory rates, oliguria, mental
      confusion.) and/or some of the following local symptoms or signs: severe
      spontaneous pain, indurated edema, bullae, cyanosis, skin pallor, absence of
      lymphangitis, skin hypoesthesia, crepitation, muscle weakness, foul smell of
      exudates. Many risk factors are suspected. A recent case-control study
      demonstrated that using ibuprofen increased the risk of cellulitis complicating
      chickenpox in children. Evidence is lower for other risk factors that are present
      with a high prevalence in most series: local lesion of skin or mucous membranes
      (acute or chronic disease, traumatism, surgery.), diabetes, arteriopathy,
      alcoholism, obesity, immunosuppression, NSAIDs. The risk of streptococcal
      necrotizing fasciitis is increased when in contact with patients infected by the
      same streptococcus.

PMID- 11319369
TI  - [Cellulitis and necrotizing fasciitis: microbiology and pathogenesis].
AB  - Streptococcus pyogenes is a common cause of necrotizing cutaneous infections in
      otherwise healthy children and adults. Several surface components are involved in
      the processes of adherence and invasiveness, such as protein M and capsulae.
      Streptolysin O and other bacterial products, such as pyrogenic exotoxins, are
      involved in tissue injury and necrosis. Toxins A and C act as superantigens and
      are expressed by strains associated with the toxic shock syndrome. Staphylococcus
      aureus, alone or in association with streptococci, is also commonly isolated form
      all body sites, but bacteremia is inconstant. Capsule, protein A, and the
      staphylococcal toxic shock syndrome toxin are the major pathogenicity factors. In
      infections of the face and the neck, the predominant anaerobes recovered in
      association with group A streptococci are Peptostreptococcus magnus, oral
      Prevotella, Porphyromonas spp., and Fusobacterium spp. Bacteroides fragilis,
      Clostridium, enterobacteria, and enterococci are recovered in infections located
      next to the perineal area. Penicillin is the drug of choice for the treatment of
      streptococcal infections. However benzylpenicillin may be not sufficient for
      severe infections and large inoculum, therefore the administration of clindamycin
      or another inhibitor of protein synthesis is recommended. Since the infection may
      be polymicrobial, the initial therapy should include treatment for staphylococci
      and anaerobes. In some cases broad- spectrum antibiotics also, effective on
      enterobacteria, are needed. The efficacy of appropriate parenteral antibiotics,
      however, depends on the prompt and aggressive exploration and debridement of
      suspected deep-seated infection, and supportive care of shock and multiple organ
      failure.

PMID- 11319370
TI  - [Subacute forms of necrotizing fasciitis and necrotizing cellulitis: diagnosis
      criteria and surgical decision-making].
AB  - Subacute cellulitis could be described as intermediary forms between benign
      erysipelas and life-threatening necrotizing fasciitis with toxic shock syndrome.
      The key point is to consider any cellulitis a possible indication for surgery.
      Subacute cellulitis may occur in the elderly or diabetic patients. Local signs
      (cyanosis, necrosis.) are sometimes isolated. They may occur during the evolution
      of cellulitis requiring a medical treatment. This emphasizes the importance of
      carefully following-up any patient treated by antibiotics for cellulitis, i.e.
      monitoring the extension of erythema (using a felt-pen) and atypical local signs.
      Complementary investigations are especially helpful when diagnosing cellulitis
      requiring a surgical treatment: fine-needle aspirations; histology; soft-tissue X
      ray; MR imaging that can detect alterations of the cutis and fascia, myositis,
      and abscesses. Surgery can be delayed for such patients, allowing for a better
      preparation. Sometimes, only surgical exploration may confirm cellulitis. Lastly,
      some cases may mimic surgical cellulitis but a prolonged course of antibiotics is
      able to control the disease. Abscesses requiring secondary surgical evacuation
      may complicate all these insidious features.

PMID- 11319371
TI  - [The therapeutic approach to necrotizing fasciitis].
AB  - Necrotizing fasciitis are characterized by the necrosis of fascias, and their
      severe consequences in terms of morbidity and mortality. An early diagnosis,
      based on sometimes subtle cutaneous lesions (associated to a sepsis syndrome)
      allows to start resuscitation and decide on a probable surgery. 3 major forms can
      be distinguished: streptococcal fasciitis, due to beta-hemolytic streptococci,
      often following minor trauma, and increasingly associated to a streptococcal
      toxic shock syndrome (STTS); clostridial gangrene (often polymicrobial when
      developed on a open wound or after surgery); and synergistic gangrene due to a
      mixed aerobic-anaerobic flora. Other apparently "primitive" necrotizing
      fasciitis, caused by specific organisms, may occur in debilitated patients. The
      prognosis depends on age, comorbidity, and above all on the severity of the
      sepsis syndrome. Initial resuscitation involves controlling the hypotension and
      organ dysfunction associated with severe sepsis, and is usually dominated by a
      severe hypovolemia. Penicillin G remains the key antibiotic for streptococcal and
      clostridial fasciitis, with a broad spectrum including enterobacteriaceae,
      streptococci and enterococci, and anaerobes (including Bacteroides spp.) in other
      types or when the etiology is unknown. In patients presenting with STSS, a
      combination of clindamycin (or rifampin) to penicillin is recommended, because of
      their effect on exotoxin production; administration of non-specific
      immunoglobulins also appears to improve the outcome of patients affected.
      Hyperbaric oxygen therapy has not proved effective. Early surgical debridement
      largely influences the prognosis. The prevention of complications associated with
      long-term intensive care, including early nutritional support and prevention of a
      thromboembolic disease, is also important.

PMID- 11319372
TI  - [Subcutaneous infection and necrotizing fasciitis of the limbs in adults.
      Surgical treatment].
AB  - We report the clinical aspect of subcutaneous cellular tissue streptococcal
      necrosis. These dramatic infections have 2 clinical aspects: superficial and
      deep. The hypodermic tissue necrosis is limited and does not affect the fascia.
      It is caused by the thrombosis of local vessels and is followed by skin necrosis.
      Necrotizing fasciitis is more dramatic and much less frequent. Anatomic
      pathophysiology concerns the soft tissue surrounding the fascia. A Streptococcus
      is involved in most of the cases for both diseases, even if this is difficult to
      demonstrate. Surgery is suggested after a short therapeutic test, if erythema
      does not regress after a few hours of penicillin-therapy. Surgery consists in
      excision of all the necrotic tissue. Deep necrotizing fasciitis calls for a
      really dramatic surgery with a high level of mortality and heavy functional
      sequels.

PMID- 11319373
TI  - [Hyperbaric oxygen for the treatment of necrotizing fasciitis].
AB  - Necrotizing fasciitis (NF) is a severe often life threatening bacterial
      infection. There are 2 main reasons to use hyperbaric oxygen (HBO2): the
      polymorphism of the bacterial flora with a predominance of anaerobes, either
      strict or aerotolerant; and the tissular necrosis due to an extensive
      disseminated microvascular obstruction within the infected area. Association of
      HBO2 to antibiotics and surgery is based on strong pathophysiological findings as
      well as on evidences from animal studies. Clinical evidence in human is still
      lacking even if published data supports its use in severe cases. Controversy on
      its use as a treatment for NF is caused more by the difficulty to dispose of a
      hyperbaric equipment allowing for the management of a patient in critical state,
      than by doubt on its real efficiency.

PMID- 11319374
TI  - [What data is needed today to deal with erysipelas?].
AB  - Erysipelas are common dermo-hypodermal infections. In spite of that, different
      questions are not clearly resolved. To improve our knowledge of this infection,
      it is important to have epidemiological, microbiological and diagnostical data.
      The current data are summarized in this article after a bibliographic research.
      The epidemiology has changed, with an increase of the number of erysipelas of the
      leg whereas face localization is less frequent. Some facilitating factors can be
      individualized, like circulatory insufficiency of the legs. There are only few
      data concerning pathophysiology. The diagnosis is mainly made on clinical
      symptoms. There is no specific diagnostic test. The bacteria that cause
      erysipelas is rarely isolated in clinical practice. The group A Streptococcus is
      the most frequent bacteria in erysipelas. It is important for physicians, to have
      a better knowledge of this infection, so that the efficacy of the treatment can
      be improved.

PMID- 11319375
TI  - [Management of erysipelas].
AB  - The objective of this literature review was to evaluate the therapeutic
      management of erysipelas. We selected 74 publications, some of written a long
      time ago, and thus open to criticism regarding their methodology. However, no
      recent or better study was available on the subject. Penicillin G remains the
      therapeutic reference. The use of macrolides and stretogramins is an alternative
      after the exclusion of severe forms of erysipelas. The preventive treatment of
      thrombosis by heparin must be discussed taking into account risk factors. More
      studies are necessary to suggest a coprescription corticoid/NSAIDs and
      antibiotherapy. The best antibiotic prophylaxis after the initial treatment
      isabenzathine-penicillin injection every 15 days.

PMID- 11319376
TI  - [What data is needed today to deal with cellulitis and necrotizing fasciitis?].
AB  - Cellulitis and necrotizing fasciitis can be distinguished by the depth of the
      cutaneous lesion and classically by the different bacteria implicated. This
      classification is not taken into account by the practitioner because of a similar
      therapeutic strategy. That is why most authors used a single title: necrotizing
      soft tissue infection. The potential severity of these infections required a
      quick diagnosis to decrease the risk of mortality and severe functional
      consequences. The analysis of the literature doesn't allow to establish the
      incidence of these infections. It was demonstrated that infections due to
      Streptococcus serogroup A increased over the last few years, thanks to a specific
      surveillance system. Risk factors leading to these infections are: cutaneous
      trauma, age, diabetes, varicella in children, contact with people infected by
      Streptococcus. The most recent studies demonstrated a frequent polymicrobism of
      the infections, with anaerobes, Streptococcus, Staphylococcus, and gram-negative
      rods. At the onset of the disease, the diagnosis is difficult to establish. Pain,
      induration of tissues, a rapid evolution, the inefficacy of antibiotic treatment
      suggest the diagnosis of necrotizing infection. MRI, when available, is a good
      technique to reveal the depth of the infection and necrosis. Surgery will confirm
      the diagnosis and allow for debridement of necrotized tissues. A delayed surgery
      increases the mortality risk factor, as stated in numerous studies.

PMID- 11319377
TI  - [Management of necrotizing cellulitis and fasciitis].
AB  - A literature review did not reveal any controlled study on the management of
      necrotizing fasciitis. Treatment protocol includes: - an immediate or early
      surgical management with debridement of all necrotic tissue and extensive
      fasciotomy followed by a surgical reexamination of the infected area in the
      following days; - an initial antibiotic therapy targeting aerobic Gram-positive
      and Gram-negative organisms and anaerobes (e.g: amoxicilline-clavulanic acid or
      vancomycin-metronidazole); - an adequate nutritional support, infusion, and
      resuscitation; - hyperbaric oxygen therapy may be considered as an associated
      treatment; but there is no randomized, controlled trial demonstrating its
      efficacy.

PMID- 11319378
TI  - [Management of erysipelas and necrotizing fasciitis].

PMID- 11319379
TI  - [Management of erysipelas and necrotizing fasciitis].

PMID- 11319380
TI  - [Is worldwide eradication of leprosy an attainable goal?].

PMID- 11319381
TI  - [From Wells syndrome to "eosinophilic disease"].

PMID- 11319382
TI  - [Histological and clinical forms of the eosinophilic cellulitis].
AB  - BACKGROUND: Wells' syndrome is characterized by clinical features of cellulitis
      and a histological picture of eosinophilic infiltrate of the dermis with some
      "flame" figures. PATIENTS AND METHODS: The clinical and histological features of
      nine patients with Wells' syndrome seen from 1988 to 1998 were retrospectively
      reviewed. RESULTS: The clinical features of the nine patients (five men and four
      women) were urticaria (n=1), cellulitis (n=2), annular plaques (n=3), vesiculo
      bullous lesions (n=2) and edema of the face with nodules of the conjunctiva
      (n=1). Histological examination of skin biopsies showed an eosinophilic
      infiltrate of the dermis associated with some "flame" figures in all cases. The
      infiltrate was located in the superficial or deep dermis in accordance with the
      different clinical features. One patient developed a non Hodgkin lymphoma and
      presented successively: a Wells' syndrome, a leucocytoklastic vasculitis and a
      Sweet's syndrome. Numerous treatment were used: topical corticosteroids, H1
      antihistamines, dapsone and systemic corticosteroids. Two patients relapsed after
      treatment withdrawal. DISCUSSION: This study demonstrated a wide polymorphism of
      the clinical and histological features of Wells' syndrome. The clinical features
      seem to depend on the location of the dermal infiltrate, suggesting the existence
      of a spectrum of eosinophilic dermatoses, like in neutrophilic dermatoses. The
      successive occurrence of vasculitis, Wells' syndrome and Sweet'syndrome in a
      patient suggests an overlap between these diseases. Systemic corticosteroids are
      the most effective treatment, but may lead to a corticosteroid dependence.

PMID- 11319383
TI  - [New cases of leprosy at the Marchoux Institute: a comparative study 1988-1997].
AB  - BACKGROUND: The prevalence of leprosy had declined greatly over the last decade.
      The purpose of this work was to determine whether changes in the epidemiology,
      clinical and bacteriological patterns occurred among patients with leprosy
      treated at the Marchoux Institute in 1988 and in 1997. PATIENTS AND METHODS: We
      conducted a descriptive cross-sectional study, reviewing retrospectively all
      files of patients with leprosy seen in 1988 in comparison with a prospective
      series of leprosy patients seen in 1997. Only new cases of leprosy, prior to
      treatment and with skin and/or nervous lesions irrespective of the bacilloscopy
      results, were included in the two series. RESULTS: We included 93 patients among
      246 patient files in 1988. There were 119 new cases in 1997. The following
      variables showed changes: mean delay to consultation (41.2 months in 1988 versus
      26.1 months in 1997; patient's suspicion of having leprosy (93 patients in 1988
      versus 22 in 1997); notion of contact (35 cases in 1988 versus 45 in 1997).
      Multibacilli leprosy predominated over paucibacilli leprosy in 1988 (51 versus 42
      cases). This trend was inverted in 1997 (44 versus 75) (p<0.009). Patients with
      grade 2 handicap were more numerous in 1988 (20 cases versus 2 cases, p<0.001).
      CONCLUSION: These findings demonstrate a change in the epidemiology, clinical and
      bacilloscopic pattern of patients with leprosy from 1988 to 1997.

PMID- 11319384
TI  - [Detection of clonal T-cell receptor gamma gene rearrangement with the use of PCR
      DGGE for diagnosis of erythroderma].
AB  - BACKGROUND: It is often difficult to establish the etiological diagnosis of
      erythroderma because clinical findings and immunohistology cannot always
      distinguish between lymphomatous erythroderma and inflammatory erythroderma. The
      purpose of this work was to assess the contribution of PCR-DGGE for detecting
      clonal T-cell receptor gamma gene rearrangement to the etiological diagnosis of
      erythroderma. PATIENTS AND METHODS: The following inclusion criteria were used:
      patient with erythroderma; skin biopsy for histologic study, immunophenotyping
      and molecular biology; minimal follow-up of 12 months after initial diagnosis.
      Thirty patients were included from May 1, 1995 to November 30, 1998. Histology
      slides were reread by one of the authors blinded to other data who classed them
      in three categories: probable lymphoma, probable inflammatory disease, uncertain
      diagnosis. Molecular data were also analyzed in the same blinded manner.
      Immunohistology diagnosis was compared with the molecular data and the final
      diagnosis retained from clinical, histological and molecular findings as well as
      the disease course to last follow-up (November 1, 1999) after a mean 12 +/- 18
      months follow-up. RESULTS: Eight biopsies were classed as probable lymphomas; a T
      cell clonal rearrangement of the TCR genes was detected in 7/8 cases. The one
      sample with no detectable T clone was a drug-induced Sezary pseudolymphoma. The
      histologial classification identified 16 cases of probable inflammatory disease;
      no clonal rearrangement of the TCR genes was found in these cases. One of these
      patients had fungoid mycosis treated with caryolysin for three months and
      developed treatment intolerance at the time of the skin biopsy. For six biopsies
      the histological diagnosis was "uncertain"; a clonal rearrangement of the TCR
      genes was found in 2/3 of the fungoid mycosis cases and in none of the three
      cases of toxic dermal reactions. DISCUSSION: This study demonstrated the
      contribution of genotypic analysis with PCR-DGGE to the diagnosis of
      erythroderma. Monoclonal TCR gene rearrangement was detected in 9/11 (82 p. 100)
      of the patients with lymphoma and in 0/19 of the patients with an inflammatory
      dermatosis. The etiological diagnosis of erythroderma is an excellent indication
      for molecular stud of skin biopsies with PCR-DGGE.

PMID- 11319385
TI  - [Acne flare-up and deterioration with oral isotretinoin].
AB  - BACKGROUND: Isotretinoin treatment for acne can lead to inflammatory flare-ups or
      an aggravation, occasionally leading to acne fulminans. The purpose of this work
      was to examine our cases and to propose a classification system for management.
      PATIENTS AND METHODS: Over a 3-year period, we selected patients referred to our
      dermatology unit for paradoxical aggravation of acne under isotretinoin
      treatment. We recorded clinical data, drug prescriptions and the course of the
      flare-up. RESULTS: Over 3 years (1995-1998) we observed 32 cases of acne flare-up
      in patients taking isotretinoin, 6 women and 26 men. DISCUSSION: Four types of
      aggravation could be identified depending on their date of onset, the skin signs,
      and the presence or not of general signs. Systemic corticosteroids are generally
      required, together with a lower daily dose of isotretinoin and local care
      (excision of open and closed comedons). Factors predictive of aggravation are
      young age, male sex and sebaceous retention. CONCLUSION: Acne fuminans is
      exceptional in patients taking isotretinoin compared with the number of patients
      treated. Clinicians should nevertheless be aware of the risk in order to make the
      diagnosis and provide appropriate care.

PMID- 11319386
TI  - [Calcipotriol].
AB  - Calcipotriol is a vitamin D derivative synthesized in 1985 by the Leo
      Laboratories. Its mode of action is identical to that of 1-25 vitamin D3
      (calcitriol), essentially by regulating the activity of genes capable of
      responding to vitamin D. Calcipotriol leads to reduction in keratinocyte
      proliferation and induces their differentiation as well as having important
      immunomodulator functions. Toxicology studies have demonstrated that phosphorus
      calcium metabolism anomalies are only observed for doses above those recommended
      for clinical use (100 g per week). The half-life of Calcipotriol is much shorter
      than that of calcitriol and its metabolites are inactive. The effects of
      Calcipotriol on phosphorus calcium metabolism are much less pronounced than those
      of calcitriol. Therapeutic trials in psoriasis have demonstrated the superiority
      of Calcipotriol over its excipient, class 2 dermatocorticoids, and reducers.
      Given in combination with phototherapy, cyclosporin or retinoids, Calcipotriol
      provides more complete improvement in lesions and allows a reduction in the
      cumulative doses of these treatments. Calcipotriol is effective in certain
      keratinization disorders (ichtyoses) as well as in localized sclerodermia and
      vitiligo, although the effect is less certain for the latter conditions. At
      recommended doses, adverse effects are limited to skin reactions with lesional
      and perilesional irritation in about 20 p. 100 of the cases. Contact dermatitis
      is rare. Photosensitivization can be observed when Calcipotriol is applied in
      patients undergoing UVB phototherapy. The marketing approval in France includes
      indications for psoriasis not involving more than 40 p. 100 of the skin surface.
      Several studies have demonstrated the efficacy and safety of Calcipotriol in
      children using the dose of 50 g per week per m2 body surface area.
      Contraindications include hypercalcemia, pregnancy and nursing. Three
      formulations are available (salve, cream, and lotion, all at 0.005 p. 100
      concentration) for different administration schemes: two applications per day,
      alternative applications with dermocorticoid or in combination with systemic
      treatment for psoriasis. Long-term treatment protocols have not been determined.

PMID- 11319387
TI  - [Intense hemosiderin deposits in a case of self-healing congenital
      histiocytosis].
AB  - BACKGROUND: Congenital self healing histiocytosis, described for the first time
      in 1973 by Hashimoto and Pritzker, is characterized by multiple violaceous brown
      cutaneous papulonodules present at birth and disappearing spontaneously in 2 to 4
      months. There are classically no systemic manifestations and the prognosis is
      always good. We present a case, particular by the intensity of hemosiderinic
      deposits. CASE-REPORT: The patient was a 2-month-old female infant. Physical
      examination at birth revealed a healthy-appearing full-term newborn, with five
      skin lesions: firm violaceous-reddish pigmented papules and nodules distributed
      over the head (scalp and forehead), right ear, right forearm and the flexural
      aspect of the left thigh. There was no hepatosplenomegaly or lymphadenopathy, and
      the patient's general condition was excellent. Histologic examination confirm the
      diagnosis by showing a dense polymorphous infiltrate composed of histiocytes
      associated with giant cells and erythrocytes extravasation. Perls stain was
      strongly positive. Staining with S100 Protein was positive. Outcome was good with
      involution of all lesions with atrophic and pigmented scars. DISCUSSION: The
      patient's excellent general condition, the absence of visceral locations and the
      spontaneous self healing allows us to classify this form as a benign self healing
      congenital histiocytosis. This patient presented intensely hemosiderinic deposits
      giving the lesions a strongly pigmented aspect.

PMID- 11319389
TI  - [Subacute cutaneous lupus gyratus repens].
AB  - BACKGROUND: Erythema gyratum repens is a rare paraneoplastic eruption. To date,
      only sixty have appeared in the literature. We report a patient with clinical and
      histological cutaneous subacute lupus and typical erythema gyratum repens. CASE
      REPORT: A 86-year-old woman presented with a 2-month history erythematous
      patches, confined mainly to the trunk, arms, thighs and the face. Cutaneous
      biopsy was compatible with cutaneous subacute lupus. After 4 weeks of
      hydroxychloroquine treatment, physical examination revealed erythematous,
      concentric, serpiginous and scaly bands on the trunk. Erythematous patches
      persisted on the limbs and the face. Physical examination and investigations in
      search of an internal malignancy were negative. All cutaneous lesions resolved
      after three months of chloroquine and dapsone treatment. DISCUSSION: Fourteen
      cases of erythema gyratum repens have been reported unassociated with underlying
      malignancy. This eruption usually precedes the occurrence of the neoplasm.
      Erythema gyratum repens is a migrating gyrate erythema with a serpiginous,
      concentric appearance creating a wood-grain look in the skin, which is
      pathognomonic. Histological findings are not specific, showing light
      parakeratosis and perivascular lymphocytic infiltrate of superficial dermis. Five
      cases of cutaneous lupus associated with erythema gyratum repens eruption have
      been reported. Considering the negative check-up in search of internal malignancy
      on a follow-up period of 20 months, our case is a probably a particular form of
      subacute lupus.

PMID- 11319388
TI  - [Methylprednisolone-induced acute generalized exanthematous pustulosis].
AB  - BACKGROUND: Acute generalized exanthematous pustulosis is a rare drug allergy.
      Generalized reactions to systematically administrated corticosteroids are even
      rarer. We report the first case of acute generalized exanthematous pustulosis due
      to methylprednisolone. CASE REPORT: A thirty year-old-woman presented, a few
      hours after intravenous administration of methylprednisolone indicated for
      multiple sclerosis, a maculopapulous rash predominant in the folds rapidly
      becoming pustulous with malaise, fever and neutrophilia. The histologic
      examination and negativity of microbiological cultures were consistent with the
      diagnostic of acute generalized exanthematous pustulosis. The rash cleared
      spontaneously in one week with normalization of the biology. One month later,
      epicutaneous tests, confirmed the allergy to group A corticosteroids. The
      treatment of multiple sclerosis was pursued with dexamethasone. DISCUSSION:
      Clinical and histological manifestations were consistent with the diagnostic of
      acute generalized exanthematous pustulosis to methylprednisolone. Generalized
      reaction to systematically administered corticosteroids are very rare. Immediate
      reactions are the most frequently reported reactions, only about thirty delayed
      type generalized skin eruptions have been reported to date. Group A
      corticosteroids are the most frequent causal agent. Epicutaneous tests have good
      sensitivity for acute generalized exanthematous pustulosis, for allergy to
      corticosteroids, delayed results are very important.

PMID- 11319390
TI  - [Hydroa vacciniforme: dietary fish oil].
AB  - BACKGROUND: Hydroa vaccinniforme is a highly uncommon photodermatosis acquired in
      childhood. The clinical course is dominated by the risk of varioliform scars.
      Numerous treatments have been proposed with variable efficacy. One recent open
      study suggested dietary fish oil could be useful. We report a case of hydroa
      vacciniforme treated successfully with dietary fish oil (Maxepa(R)). CASE REPORT:
      A 15-year-old girl consulted in May 1988 for vesiculobullous lesions typical of
      hydroa vacciniforme in photo-exposed areas. Anti-malaria drugs and
      photoprotection had been used for several years without success. Maxepa(R) was
      introduced in June 1998 and was followed by regression of the lesions within a
      few weeks despite the summer season. The treatment was interrupted at the
      patient's request due to fetid breath. Reintroduction of Maxepa(R) in April 1999
      after an episode of recurrent lesions, again led to total resolution of the
      lesions within three weeks. DISCUSSION: Hydroa vacciniforme is an exceptional
      photodermatosis of uncertain etiology. It may possibly be related to an abnormal
      sensitivity to ultraviolet A. Fish oil rich in 3-omega polyunsaturated fatty
      acids would reduce the local inflammation triggered by sun exposure. Recent
      studies have demonstrated that dietary fish oil can increase the level of 3-omega
      polyunsaturated fatty acids in the epidermis and reduce the level of
      prostaglandins in the skin. Our case would appear to confirm the contribution of
      dietary fish oil to treatment despite the poor tolerance due to fetid breath.

PMID- 11319391
TI  - [Mycobacterium kansasii skin infection at insulin injection sites].
AB  - BACKGROUND: Insulin injection sites rarely become infected. We report a case of
      Mycobacterium kansasii infection at the sites of insulin injection. CASE REPORT:
      An 84-year-old woman with insulin-dependent diabetes consulted for lesions on the
      anterior aspect of the thighs. She had papulonodules at the sites of insulin
      injection. These lesions progressed to hard fibrinonecrotic ulcerations with a
      raised erythematous border. There were no enlarged nodes locally. Laboratory
      tests were normal. Bacteriological samples were negative at direct examination.
      Histology was not specific. The biopsy cultures finally found an atypical
      mycobacteria, Mycobacterium kansasii. The clinical course was favorable with
      clarithromycin alone. DISCUSSION: Only 35 cases of Mycobacterium kansasii skin
      infections have been reported in the literature. This is the first case observed
      in a diabetic subject and the first treated with clarithromycin alone. This case
      illustrates the potential, though exceptional, risk of insulin bottle
      contamination by an environmental germ.

PMID- 11319393
TI  - [Is ophthalmologic screening essential during alpha interferon treatment?].

PMID- 11319392
TI  - [Cutaneous blastomycosis revealing a corticoadenoma].
AB  - BACKGROUND: Blastomycosis is an uncommon chronic granulomatosis caused by
      Blastomyces dermatitidis. We present a case with a skin localization that
      disclosed malignant corticoadenoma. CASE REPORT: A 32-year-old man consulted for
      inflammatory nodules of the face and lower limbs. The histological examination of
      a nodule biopsy was in favour of blastomycosis. Ketoconazole treatment was
      ineffective. Amphotericin B provided cure of the skin lesions. Search for
      extension disclosed a malignant corticoadrenoma. DISCUSSION: Blastomycosis is
      very rare in Morocco. The portal is usually the lung. Unique skin involvement is
      very exceptional. To our knowledge this is the first report of a blastomycosis
      corticoadenoma association. The clinical situation may be alarming in
      immunodepressed subjects. Amphotericin B treatment is indicated.

PMID- 11319394
TI  - [Ophthalmologic screening during alpha interferon therapy: how and why?].

PMID- 11319395
TI  - [Skin pathology examination: a small contribution from Belgium to Pr Grosshans'
      editorial].

PMID- 11319396
TI  - [Transverse nasal line in childhood].

PMID- 11319397
TI  - [Ungueal and periungueal lesions].

PMID- 11319398
TI  - [Pilomatrixoma].

PMID- 11319399
TI  - [Collodion baby syndrome].

PMID- 11319400
TI  - [Acquired bullous epidermplysis].

PMID- 11319401
TI  - [Lichen striatus].

PMID- 11319402
TI  - [Asymmetric vulvar pigmentation in a 51-year-old woman].

PMID- 11319403
TI  - [Second intention healing: indications and practical use].

PMID- 11319404
TI  - [Treatment of childhood psoriasis].

PMID- 11319405
TI  - [Anetoderma secondary to juvenile xanthogranuloma].

PMID- 11319406
TI  - [Tympanic grafts: surgical techniques and results of 260 cases].
AB  - PURPOSE OF STUDY: The aim of this retrospective survey was to define factors
      which may influence tympanic grafts results. METHODS: 260 surgical procedures
      were retrospectively analyzed between 1992 and 1997 by studying anatomical and
      functional results with a mean follow-up of 18 months. RESULTS: Global rate of
      tympanic grafts reperforation was 9.2%. At 18 months, the air conduction gain was
      9.5 +/- 11.5 dB, with an 13 +/- 7.7 dB air-bone gap (ABG) and 80% ABG inferior to
      20 dB, the change in air bone gap was 9 +/- 10.3 dB. Several factors influencing
      the results were identified: second hand surgical procedures (40%) had worse
      functional results than patients from first hand procedures, inflammatory atrial
      mucosa or obstruction of the eustachian tube (more graft retraction), retracted
      malleus handle and/or stuck to the promontory (worse auditory results), temporal
      aponeurosis placed under malleus handle (more reperforation of the graft without
      hearing difference as to graft placement above malleus handle), association of
      canal wall-down technique (poor auditory results), surgeon experience (better
      auditory results). CONCLUSION: A first surgical procedure, normal malleus handle
      and atrial mucosa, no mastoidectomy or canal wall-up technique, a temporal
      aponeurosis graft placed above malleus handle are predictive factors for
      anatomical and/or functional good results.

PMID- 11319407
TI  - [T3 and T4 cancer of the oral cavity, surgical treatment with oral tongue
      resection].
AB  - Amputation of the oral tongue is required to treat T3 and T4 bilateral tumors of
      the anterior two third of the tongue with or without extension to the floor of
      the mouth. This partial glossectomy was performed initially for 27 patients and
      as salvage therapy for 35 patients with recurrent diseases. The reconstruction
      required a flap in all cases, including 8 microvascular free flaps. Two months
      after surgery, two third of patients had a satisfactory swallowing hability. The
      functional results were worst for patients operated after radiotherapy. Actuarial
      survival rates were 37.5% and 22.1% at 3 and 5 years respectively. The survival
      rate of patients who had surgery as primary modality of treatment was
      significantly better as compared with those who had radiotherapy before surgery
      (p=0,018). This surgery offers a perfect control of tumors of the anterior floor
      and oral tongue and good rehabilitation provided by the conservation of the
      posterior tongue.

PMID- 11319408
TI  - [Articulatory compensation after supracricoid partial laryngectomy with
      cricohyoidoepiglottopexy].
AB  - OBJECTIVES: The consequences of the modification of the glottis and the
      shortening of the vocal tract after supracricoid partial laryngectomy (SCPL) with
      cricohyoidoepiglottopexy (CHEP) were investigated prospectively on ten patients.
      An acoustic analysis of the transfer function of the vocal tract was performed by
      measuring the formant frequencies of the [a] and [i] vowels. The articulation
      compensatory mechanisms of the vocal tract were observed with cinefluoroscopy in
      order to evaluate the phonation and articulation constraints. PATIENTS AND
      METHODS: Ten male patients were recorded before surgery and at six, 12 and 18
      months after surgery. The results were compared with those of 10 male normal
      speakers having the same range of age. For the acoustic measures, we tracked the
      three first formant frequencies of the cardinal vowels [a] and [i], before and
      after surgery. Articulation investigation was performed with cinefluoroscopy for
      the vowels [a] and [i] uttered by two of the 10 patients. RESULTS: For the [a]
      vowel, the acoustic analysis showed higher values for all three formants, related
      to the shortening of the vocal tract after surgery. For the [i] vowel, the
      lowering of the second formant frequencies after surgery was related to an
      articulatory compensation. Cinefluoroscopy confirmed the shortening of the vocal
      tract, the tongue-root retraction for voicing and the anterior position of the
      tip of the tongue for the [i] vowel. CONCLUSIONS: The consequences of the
      shortening of the vocal tract after SCPL with CHEP can be evaluated, non
      invasively, by means of acoustic analysis. The understanding of the articulation
      compensatory mechanisms resulting from voicing constraints should help voice
      rehabilitation and improve oral communication in such patients.

PMID- 11319409
TI  - [Neonatal deafness screening with the evoked otoacoustic emissions technique.
      Study of 320 newborns at the neonatal resuscitation service of the Amiens
      neonatal care unit].
AB  - Between January 1997 and June 1999, we screened for hearing loss using evoked
      otoacoustic emissions in 320 newborns in the neonate intensive care unit at the
      Amiens University Hospital. The purpose of this study was to search for
      correlations between deafness and one of the hearing loss risk factors identified
      by the Joint Committee on Infant Screening. Three risk factors were found to be
      significant: craniofacial abnormalities, low birth weight (less than 1500 g) and
      a familial history of hearing loss. Unfortunately a large proportion of the
      infants were lost to follow-up. Evoked otoacoustic emission provide an excellent
      screening technique for hearing loss in newborns. Such screening implies however
      the creation of networks to assure patient follow-up.

PMID- 11319410
TI  - Benign paroxysmal positional vertigo, incidence and treatment.
AB  - Benign paroxysmal positional vertigo is characterized by acute vertigo that is
      accentuated by movements of the head. It can be identified by the presence of
      nystagmus triggered by certain head positions. Over a 1-year period, among 1,902
      cases of different types of equilibrium disorders, there were 98 cases of BPPV
      including 63 BPPV ofthe posterior canal, 21 of the lateral canal, 13 combined (HC
      + PC) and one case affecting the anterior canal. Most of the cases were
      idiopathic. Treatment was based on the Semont maneuver for BPPV-PC. BPPV-HC was
      treated with the Vannucchi maneuver and a personal method. The one case of BPPV
      AC was treated with a modified Semont maneuver. Satisfactory therapeutic results
      were noted in all cases. Cases with a long-term follow-up showed a high
      percentage of elimination of relapse after 24 months.

PMID- 11319411
TI  - [Use of neck platysma myocutaneous flap for reconstruction substance defects
      after surgical resection of oropharyngeal tumors. Report of 70 cases].
AB  - PURPOSE OF THE STUDY: We analyzed our experience with the cervical platysma
      myocutaneous flap and reviewed the pertinent literature. We evaluated the
      harvesting technique, surgical indications, reliability of the flap, its
      advantages and drawbacks compared with other reconstruction techniques and
      assessed survival and local control. MATERIALS AND METHODS: This retrospective
      series included 70 patients with a mean 83-month follow-up. All patients had an
      oral cavity or oropharyngeal carcioma ranging from T1 to T4, N0 to N2b according
      to the TNM classification. All underwent one-step surgery with unilateral or
      bilateral type III elective neck dissection, followed by tumor resection, and
      reconstruction with a cervical platysma myocutaneous flap. RESULTS: Complications
      related to flap reliability were observed in 17 cases (24.3%): 1 total necrosis
      (1.4%), 6 partial necrosis (8.6%), and 10 paddle epidermolysis (14.3%). Median
      survival and local control were 35 and 59 months respectively. Eight out of 55
      preoperative N0 patients were histologically N+ (14.5%). No significant
      difference in risk of metastasis recurrence was evidenced between N0 and N+
      patients (p > 0.05). DISCUSSION: Reconstruction after ablation of oral or
      oropharyngeal cancer using a cervical platysma myocutaneous flap can be easily
      combined with an elective neck dissection without increasing the risk of
      recurrence. The flap must preserve the facial artery and its submental branch and
      the external jugular vein to ensure reliability. When indications are strictiy
      applied, the properties of the platysma plasty and the anterolateral cervical
      situation provide very satisfactory functional and esthetic results.

PMID- 11319412
TI  - [Laryngomucoceles and subtotal C.H.E.P. reconstructive laryngectomy. Report of 6
      cases].
AB  - We conducted a retrospective analysis of 131 patients who underwent subtotal CHEP
      laryngectomy for a tumor of the larynx between 1990 and 1999 in order to
      determine the incidence of laryngomucocele after surgery. RESULTS: Five patients
      developed laryngomucocele late after surgery. A sixth patient underwent surgery
      in another unit. Laryngomucocele developed progressively or was disclosed by
      acute episodes of dyspnea, requiring tracheotomy again in two cases. One patient
      developed bilateral mucocele. Three patients had cervicotomy, and three others
      were treated by CO(2) laser endoscopic marsupialization. DISCUSSION: We discuss
      the pathophysiology of late laryngomucocele after subtotal laryngectomy and
      various techniques that can be used to avoid this complication. CONCLUSION:
      Although exceptional, laryngomucocele generally requires surgical removal by
      cervicotomy or CO(2) laser endoscopic marsupialization to prevent acute
      respiratory failure.

PMID- 11319413
TI  - [Leg ulcers and cancer. 6 case reports].
AB  - OBJECTIVE: It is estimated that 1 leg ulcer out of 300 is a carcinoma. In the
      literature ulceration of skin cancer is distinguished from chronic leg ulcers
      although this later category remains a subject of debate. We examined the
      clinical features of suspected malignant leg ulcers and discuss the notion of
      secondary malignant transformation of leg ulcers. PATIENTS AND METHODS: This
      study included patients attending the Vascular Clinic at the Saint-Joseph
      Hospital in Paris between 1991 and 1999 who were referred for leg ulcers and
      whose final diagnosis was cancerous ulceration. RESULTS: There were six patients,
      mean age 77 years who had squamous cell carcinomas (4 cases) and basocellular
      carcinomas (2 cases). We observed two distinct situations: leg carcinomas that
      ulcerated from onset (2 cases) and malignant transformation of a cicatrix, known
      as Marjolin's ulcer (4 cases). There were no cases of malignant transformation of
      chronic leg ulcers in this series. The clinical elements suggestive of a
      cancerous leg ulcer were the absence of a vascular etiology, the red, budding
      aspect of the ulcer with hard borders, and its development on a cicatrix.
      CONCLUSION: Malignant transformation of a vascular leg ulcer was not observed in
      our series, but has been reported in the literature although a critical analysis
      of reported data is only significant for squamous cell carcinoma. The frequency
      is probably overestimated. Our series enabled us to identify the clinical
      circumstances leading to an early diagnosis of carcinoma of the lower limbs.
      There are three essential criteria: analysis of the vascular status of the
      patient, the clinical characteristics of the leg ulcer, and its development on a
      cicatrix.

PMID- 11319414
TI  - [Three-dimensional reconstruction calibrated with ultrasonographic images.
      Application to the measurement of clot volume in vitro].
AB  - OBJECTIVE: We used 3D ultrasonographic reconstruction with manual acquisition to
      study the volume of venous clots in vitro. MATERIAL AND METHODS: Native 2D
      ultrasound slices were acquired free hand for 3D reconstruction. The spatial
      coordinates of each slice were delivered in real time with an electromagnetic
      captor. We applied a standard ultrasound protocol to test the calibrated 3D
      reconstruction quantitatively. The volume of 5 clots of increasing size was
      quantified in vitro using manual segmentation in a double-blind manner by two
      independent operators. RESULTS: The comparison tests and the interoperator
      regression lines evidenced good agreement between real and measured volumes,
      confirming the coherence of the reconstruction protocol and the feasibility of
      this technique in a routine medical setting. Intraoperator variability was 7 to
      11% and interoperator variability 16.9%. CONCLUSION: This calibrated 3D
      reconstruction is compatible with in vitro measurement of venous clots. This
      technique could be useful to follow the evolution of the head of proximal deep
      vein thrombi in vivo. It will be more reliable with semi-automatic or even
      automatic segmentation becomes available.

PMID- 11319415
TI  - [Incidence of erysipelas of the lower limbs in a spa resort. Efficacy of a
      strategy of sanitation education (La Lechere: 1992-1997)].
AB  - OBJECTIVE: Erysipela is a common skin infection readily found in patients with
      venous insufficiency or lymphedema. The aim of this work was to measure the
      incidence of erysipela in a spa resort specialized in the treatment of venous and
      lymphatic diseases and to evaluate the influence of a preventive strategy
      principally based on education of patients at risk. PATIENTS AND METHODS: The
      measurement of incidence was based on the detection of the reasons for which the
      patients did not attend their thermal care sessions. Quality control was obtained
      from the reports of cases diagnosed by local private and public health care
      centers. RESULTS: The incidence of erysipela in this high risk population was
      40.2 and 48.5 cases for 1000 persons per exposure-year in 1993 and 1994
      respectively. The preventive strategy carried out was able to induce a reduction
      of 65% during the next years (p<0.01). CONCLUSION: This study confirms the high
      incidence of erysipela in subjects with severe venous insufficiency or lymphedema
      and the efficacy of an active educational preventive strategy.

PMID- 11319416
TI  - [Blunt trauma to the infrarenal abdominal aorta with neurologic lesions. Case
      report and review of the literature].
AB  - We report the case of a 31-year-old female involved in a severe motor vehicle
      accident. The diagnosis of blunt trauma to the abdominal aorta was not retained
      initially. The patient was referred to our institution when she developed a
      delayed paralysis of the lower limbs associated with the disappearance of both
      femoral pulses. Computed tomography evidenced dissection of the infrarenal aorta
      and NMR ruled out injury to the spinal cord. An aortoiliac endarteriectomy was
      then performed. Neurological recovery was partial at 3 months. We reviewed the
      frequency, the mechanisms and the management of blunt trauma to the abdominal
      aorta.

PMID- 11319417
TI  - [Are rheological markers of poor prognosis present in diabetic arteriopathies?].
AB  - One of the traits of type I and II diabetes lies in the presence of extensive
      rheological disorders. Rheological changes appear during infancy, mainly in type
      I diabetes: decreased red cell deformability, leukocyte rigidity, monocyte
      activation, alteration in microvessel flux (sludge) and functions. Such disorders
      are however sensitive to insulin and metabolic correction for a long period.
      Macrorheological disorders develop at the time of puberty and when lipid changes
      and vascular complications appear (hypertension, visceral obesity,
      atherosclerosis). Such changes have potent effects on diabetic arteriopathy, as
      shown by altered TcPO(2). Numerous medical teams are taking into account red cell
      aggregation measurements reflecting post-capillary flux behavior. In addition, a
      proposed score may be used based on fibrinogen, hematocrit, triglycerides as
      viscosity acting factors, and endothelial markers, Willebrand factor and VCAM-1.
      An increased score is an indication of suspected distal functional alteration of
      microvessels.

PMID- 11319418
TI  - [Critical analysis of vascular explorations in diabetic complications].
AB  - Diabetes mellitus is the chief medical cause of amputation. The risk of
      amputation is 15-fold higher in diabetic subjects and 5 out of 6 amputees are
      diabetic. Among the three risk factors for amputation in diabetic patients
      neuropathy, ischemia, and infection-ischemia is the most difficult to quantify.
      Thus, functional and/or distal foot arteriopathy may be present without any
      clinical symptoms long before trophic changes occur. Therefore additional
      vascular explorations, including measurement of systolic toe pressure, must be
      performed. Physical examination is sufficient to diagnose lower limb arterial
      disease when ankle pulses are missing, but severe foot ischemia may be present
      despite minimal clinical signs and normal ankle pulses. Mediacalcinosis alters
      ankle pressure. Toe pressure is the most reliable test for quantifying ischemia
      of the diabetic foot. Other investigations such as TcPO(2) measurement, laser
      Doppler and capillaroscopy are useful for revealing early functional diabetic
      microangiopathy, but they can only be done and interpreted in specialized
      centers.

PMID- 11319419
TI  - [Diabetic angiopathy: the role of microvascular exploration in routine practice.
      Consequences of a new algorithm for care of the diabetic foot].
AB  - Diabetes mellitus is the chief medical cause of amputation. The risk of
      amputation is 15-fold higher in diabetic subjects and 5 out of 6 amputees are
      diabetic. There are three types of clinical presentation of diabetes
      neurological, infectious and ischemic. In clinical practice, these three forms
      are often intertwined but the most frequent clinical sequence of events is
      neuropathy --> ulceration --> infection --> amputation. In this sequence,
      ischemia is not mentioned. The explanation is that the ischemic component of the
      diabetic foot is only recognized when ankle pulses are missing and when duplex
      scanning shows stenosis or occlusion of the main arterial trunks of the legs.
      This manner of diagnosing the ischemic component of diabetic foot is wrong as it
      fails to recognize the possibility of distal diabetic arteritis. Some experts in
      diabetology deny the existence of this arteritis which is obvious for those who
      measure systolic toe pressure. This distal arteritis is present in about 15% of
      all diabetic patients without trophic changes and in 35% of those with trophic
      changes. This foot arteritis is closely related to neuropathy. Toe pressure is
      not usually mentioned in text books or in consensus conferences concerning the
      diabetic foot. This is the main explanation for the calamitous number of
      amputations among diabetic patients. Nothing will change as long as physicians do
      not include toe pressure as a useful diagnostic tool in patients with diabetes.
      We present here a four-stage algorithm including toe pressure measurement for the
      management of the diabetic foot.

PMID- 11319420
TI  - [Necessary multidisciplinary management of diabetic foot].
AB  - The pathogenesis of diabetic foot is multifactorial and optimal management
      requires a multidisciplinary team. In most cases, the diabetic foot complication
      is seen as a wound subsequent to trauma, less often as an acute neuroarthropathy
      or cellulitis without any apparent skin lesion. Patients look for medical care
      more or less rapidly, depending on the information received previously concerning
      foot problems. The patient may consult a general practitioner or sometimes
      directly attend a diabetic foot clinic. The efficiency of treatment depends on
      early diagnosis, a specific etiology-guided approach to wound care and management
      of diabetes mellitus. A multidisciplinary team is needed to provide optimal care
      for foot wounds and neurological, vascular and infections complications, and to
      control blood glucose in a global approach to management of the diabetic patient.
      The team must coordinate the actions of its different members, the goal for all
      being to obtain not only foot healing but also optimal foot function. This
      requires experience in surgery of the diabetic foot. Creation of special diabetic
      foot units has been proposed to manage diabetic patients with foot pathologies as
      outpatients or inpatients when necessary.

PMID- 11319421
TI  - [Diabetic arteriopathy. Microcirculation, an inevitable therapeutic objective].
AB  - The most severe stages of arteriopathy often involve multifocal macrovascular
      lesions leading to defective perfusion of the distal tissues and subsequent
      dysfunction of the microcirculation. Diabetic autonomous neuropathy facilitates
      and aggravates this endothelial dysfunction. Loss of vasomotricity, platelet and
      white cell activation, and cytokine release lead to an obstruction of the
      capillaries and alteration or even destruction of the endothelium. At this stage,
      the lesions are irreversible and tissue vitality is definitively compromised. The
      goal of medical treatment is to delay the development of dysfunction and
      subsequent destruction of the microcirculation before, during and after
      restoration of sufficient flow through the macrocirculation lesions by
      angioplasty and/or surgery. Extrapolating from in vitro and animal studies, two
      mediators, EDRF (NO) and prostacycline, could theoretically inactivate
      inappropriate activated cells and re-establish flow. Besides their vasodilator
      proprieties, NO and prostacycline have a synergetic inhibitory effect on platelet
      and leukocyte activation. The role of platelet antiaggregates and heparins in
      this stage of severe chronic ischemia remains to be determined. The relative
      failures of therapeutic drug trials conducted since the end of the eighties
      demonstrates the importance of intervening before the microcirulation disorders
      become too severe. Until new compounds are developed, therapeutic progress can be
      achieved by more precise and earlier detection of alterations in the
      microcirculation to enable optimal management of arteriopathy of the lower limbs
      with surgery or angioplasty.

PMID- 11319422
TI  - [Current techniques for the clinical evaluation of the microcirculation].
AB  - Three main types of approaches are currently used for the exploration of the
      microcirculation in man: Clinimetric measurements of the cutaneous temperature
      (thermometry), skin color (chromametry) and tissue volume (leg or foot volumetry)
      allow a quantification of clinical indexes of skin blood flow, blood volume and
      edema that are useful in therapeutic trials. Global parameters evaluating the
      hemodynamic or nutritional efficacy of the microcirculation in a tissue sample
      (laser Doppler and TcPO(2)) are easy to perform in clinical routine. TcPO(2)
      measurements through Clarke electrodes or fluorescence lifetime imaging
      technology evaluate the nutritional efficacy of the microcirculation. Laser
      Doppler devices are producing a semi-quantitative index of superficial tissue
      perfusion, that can be split into a volumic and a velocimetric components; its
      high sensitivity makes it a valuable tool for clinical research, mainly for
      dynamic measurements of reactivity of the superficial microcirculation to various
      stimuli. New instruments are able to use two different frequencies in order to
      compare tissue perfusion at different depths beneath the skin surface. The
      combination of a laser probe and a small automate can produce a two-dimensional
      image allowing the evaluation of spatial heterogeneity in tissue perfusion.
      Visualization of the skin capillary bed, i.e. capillaroscopy, was recently
      improved by the emergence of flexible videomicroscopes easily allowing the
      exploration of the whole body skin surface and not only the classical site of the
      nailfold. The use of the method was therefore broadened from vascular
      acrosyndromes and connective tissue diseases to the whole spectrum of skin
      trophic changes of the extremities. Combination with digital image analysis
      systems allows the quantification of the microvascular and microlymphatic
      structure (quantitative appraisal of microangiopathies) and function (capillary
      hemodynamics and exchange). Laser-doppler and capillaroscopy can also be combined
      for the measurement of red blood cell velocity in single capillaries.

PMID- 11319423
TI  - [Impact factor or do we have to choose between the impact factor and the Revue de
      Chirurgie Orthopedique?].
AB  - It is common practice to evaluate the scientific value of a candidate for a
      university or hospital position using the mean of the impact factors of the
      journals he/she has published in. This shows that the true composition and true
      meaning of the impact factor are not sufficiently understood. The impact factor
      was invented in the 60s to help librarians choose the most read journals. The
      impact factor provides an accurate definition of the distribution of a journal,
      but in no case the quality of its publications. Moreover, the impact factor has
      many technical limitations that are detailed in this article. This strongly
      limits the accuracy of the impact factor to compare between journals of different
      specialties. There is no correlation between the scientific value of a single
      author and the impact factor of the journals he/she has published in. Eugene
      Garfield, the inventor of the impact factor, has emphasized that it should not be
      used to judge the scientific value of a candidate.

PMID- 11319424
TI  - [One-segment interbody lumbar arthrodesis using impacted cages: posterior
      unilateral approach versus posterior bilateral approach].
AB  - PURPOSE OF THE STUDY: We assessed the relative advantages of unilateral versus
      bilateral posterior approaches for lumbar spine fusion. MATERIAL AND METHODS:
      Eighty-three patients who underwent lumbar spine fusion via a bilateral posterior
      approach and who had reached more than two years follow-up were compared with 80
      patients who had undergone the same procedure via a unilateral posterior
      approach, including 54 with a follow-up greater than one year and 24 greater than
      two years. Most cases were L4-L5 fusions for degenerative spondylolisthesis or
      recurrent discal herniation with instability. Two composite carbon cages were
      filled with autologous cancellous bone. The key to the unilateral approach was
      the comfortable exposure of the disc by lamino-arthectomy; the osteosynthesis
      could then be performed unilaterally if only one gutter was opened. We measured
      bleeding and operative time to quantify surgical difficulty. At one year we
      assessed disc height, lordosis, frontal balance, and fusion of the operated disk.
      At two years, we assessed lombalgia and sciatalgia [scored from 4 (none) to 0
      (intolerable)], subjective outcome, and recovery of former activity level.
      RESULTS: Mean blood loss and operative time were 360 ml and 162 min for the 83
      classical procedures and 216 ml and 118 min for the 80 unilateral procedures.
      There were ten dural wounds with the bilateral approach and one dural wound and
      one transient radicular deficit with the unilateral approach. At one year, 81 of
      the 83 unilateral cases had reached fusion (2 nonunions). There was a mean 2
      degrees gain in discal lordosis despite three cases of impaction due to
      osteoporosis. For the unilateral procedures, all 54 reached fusion at one year
      with a mean 2.5 degrees gain in lordosis, also with 3 impactions. With
      intersomatic distraction, balanced disc height in the frontal plane was obtained
      in all cases where the initial narrowing was not excessive. There were no cases
      of posterior displacement. There was a degradation of the supra-adjacent segment
      in three of the bilateral cases and one of the unilateral cases. At two years,
      the mean pain score for the bilateral cases was 3.88 for lombalgia (1.22
      preoperatively) and 3.51 for sciatalgia (1.30 preoperatively). For the unilateral
      cases, lombalgia improved from 1.57 to 3.62 and sciatalgia from 0.98 to 3.79. the
      difference between the two approaches was significant for sciatalgia (p<0.01).
      The subjective assessment for the bilateral cases was: good 34, improved 43,
      unchanged 4, worse 2. For the unilateral cases it was: good 10, improved 11,
      unchanged 2, worse 1. Thirty of the 54 active patients in the bilateral group
      returned to their former work at a mean 8.5 months and 11 of the 17 active
      patients in the unilateral group did so at a mean 7.5 months. DISCUSSION: The
      unilateral approach simplifies the spinal fusion procedure. Fusion conditions and
      delay to consolidation as well as the final outcome appear to be better for
      sciatalgia. CONCLUSION: Adapted instrumentation (cages and instruments) allow
      using this simplified technique for many patients with an indication for
      classical bilateral access fusion.

PMID- 11319425
TI  - [Reconstruction by graft and reinforcement device in severe aseptic acetabular
      loosening: 10 years survivorship analysis].
AB  - PURPOSE OF THE STUDY: We report our experience with the treatment of aceptic
      acetabular loosening with important loss of bone stock using a graft and a
      metallic reinforcement device. MATERIAL AND METHOD: We carried out a
      retrospective study on 56 acetabular revision arthroplasties with severe loss of
      bone stock performed between November 1980 and June 1992. Mean age of the 35
      females and 19 males was 68.5 years. In all cases, there was a combined lesion
      (cavity + segmentary) of two roofs (type 3 or 4 in the SOFCOT classification).
      The superior wall was concerned in all cases (80 p. 100 with a combined lesion).
      Reconstruction was performed using grafts (autograft (n=15), allograft (n=39) or
      both (n=2)) covering more than 50 p. 100 of the socket. Structural grafts were
      embedded into the defects in case of superior combined lesion with extension to
      the anterior and the posterior walls. A morselized graft was used to fill other
      defects. The reinforcement device was a Muller ring (n=35) or the Burch-Schneider
      APC (n=21). Mean follow-up was 8.75 years (range 3 - 16 years). RESULTS: There
      were 29 iterative aseptic loosenings of acetabular component revised or non
      revised (n=11). Twenty-four of these cases had a Muller ring and 5 had a Burch
      Schneider APC. The 10-year cumulative survival rate (CSR) was 0.43 +/- 0.16 and
      the 11-year CSR was 0.350.16 using iterative aseptic loosening as the end point.
      The lateral position of the hip center (p=0.02), female gender (p=0.03), and the
      Muller ring (p=0.0054) were statistically negative factors. The 10-year CSR was
      0.44 +/- 0.18 for the Muller ring and 0.78 +/- 0.1 for the Burch-Schneider APC,
      the difference being statistically significant (p=0.007). These two populations
      were strictly comparable. CONCLUSIONS: In case of important loss of bone stock,
      reconstruction by grafts is widely used as reported in the literature. A metallic
      reinforcement device must be used to protect the graft during incorporation and
      to prevent late resorption. Compared with the Muller ring, the Burch-Schneider
      APC is much more adapted to meet these requirements, particularly when the graft
      covers more than 50 p. 100 of the socket.

PMID- 11319426
TI  - [Bone reconstruction, leg length discrepancy, and dislocation rate in 52 Wagner
      revision total hip arthroplasties at 44-month follow-up].
AB  - PURPOSE OF THE STUDY: The primary and secondary stability of a revision implant
      is highly compromised in cases with important loss of bone stock from the
      proximal femoral after severe femoral loosening. Several methods using implants
      with or without cement have been proposed for reconstruction after femoral bone
      loss. The purpose of this study was to analyze mid-term clinical and radiological
      outcome with the Wagner prosthesis for revision surgery. MATERIAL AND METHODS:
      Fifty-two cases of aseptic femoral loosening were treated with this method in 36
      women and 14 men, mean age 70 years (range 32-92 years). None of the patients was
      lost to follow-up; five who died after 18 months were retained for analysis. Mean
      follow-up was 44 months (range 18-88 months). The mean preoperative Postel Merle
      d'Aubigne (PMA) score was 10.5 +/- 0.4. These patients had major bone loss (5
      grade II, 24 grade III, 23 grade IV in the SOFCOT classification). The
      transfemoral access was used in 17 cases and bone grafts in 32. Clinical outcome
      was assessed with the PMA score and leg length discrepancy was measured.
      Radiographically, stability was assessed by measuring stem impaction and
      progression of radiolucent lines. RESULTS: The overall functional score was
      significantly improved from 10.5 +/- 0.4 preoperatively to 14.6 +/- 0.5
      (p<0.001). All items on the score improved but pain relief was the most notable.
      Improvement in the gait score was limited due to persistent limping in 39
      patients. Leg length discrepancies were found in 8 patients with 6 shortenings
      and 2 lengthenings. The clinical situation remained stable after one year. The
      implant remained stable in 48 patients (92 p. 100) and stem impaction was
      observed in 4 before 12 months. Two of these cases required a second revision.
      Metaphyseal reconstruction was observed in 42 patients (81 p. 100), including 24
      (46 p. 100) who exhibited homogeneous reconstruction with trabeculation. The
      reconstruction did not progress further after 18 months postoperatively.
      Complications included four dislocations and five revision procedures (three for
      cup loosening, two for femoral pivot instability). DISCUSSION: The functional
      outcome was similar to results reported in the literature, including the high
      frequency of limping that was caused by various factors (valgus prosthesis neck,
      leg length discrepancy, muscle deficits). Leg length discrepancies resulted from
      defective positioning or impaction at loading. Standard radiographic series
      allowed an assessment of stem impaction. Our low rate could be due to delayed
      weight bearing. La reconstruction of bone loss did not progress after 18 months
      and was independent of bone grafting, route of access, and the initial degree of
      loosening. The high frequency of dislocations with this type of implant can be
      prevented by horizontalization of the acetabulum and use of anti-dislocation
      inserts at the first intention revision. CONCLUSION: Our results with the Wagner
      prosthesis are satisfactory both clinically and radiographically. The two
      drawbacks of this implant (limping and dislocation), partly due to the design of
      the femoral stem, have led us to study a new implant that preserves good distal
      anchoring and optimizes the proximal biomechanics of the hip joint.

PMID- 11319427
TI  - [Shock absorption by intermediate hip prostheses].
AB  - PURPOSE OF THE STUDY: The bipolar prosthesis was developed in an attempt to
      alleviate acetabular wear of conventional metallic endoprostheses. The prosthesis
      was designed to achieve low-friction metal-on-polyethylene inner bearing motion
      while decreasing shear stress across the acetabular cartilage. Although good
      clinical results were obtained, the principle of a persistent inner mobility was
      contested and some authors have assigned the delay of cartilage erosion to the
      shock absorption capacity of the polyethylene. The present study was focused on
      assessing the vibration and shock damping effect of metal monoblock and bipolar
      head prostheses. MATERIAL AND METHODS: The transmission of the shock wave through
      these two types of prostheses was studied in vitro. The two heads were first
      tested in a rigid environment to eliminate all external parasite frequencies. The
      impact excitation was applied with a hammer connected to an oscillometer. A
      second accelerometer was connected to the prosthesis stem. Shock wave
      transmission was analyzed. Secondly, the head was tested with a system vibrating
      in the same order of frequencies as the skeleton, with and without pre
      constraint. The frequency response functions were analyzed. RESULTS: For the
      metallic prosthesis, the frequency of vibration recorded on the femoral stems was
      in a large frequency range from 0 Hz to 10 KHz. For the bipolar prosthesis, all
      the high frequencies of the shock wave were eliminated and only shock wave
      frequencies from 0 to 500 Hz were recorded. In an environmental system vibrating
      below 100 Hz, the metallic head did not express high frequencies of vibration.
      The coefficient of shock absorption was not significantly different for the two
      heads. DISCUSSION: In the first rigid environment, the metallic head did not
      filter the high frequency components of the shock wave and the bipolar head
      tended to eliminate high frequency components due to the flattening effect of the
      impulse load by the polymer. But, the lower leg is not a rigid structure and the
      musculo-skeletal system vibrates in frequencies below 100 Hz. In similar
      conditions, the increased shock-absorbing effect of the polyethylene is far more
      difficult to observe. For the metallic prosthesis, the recorded frequency of
      vibration also belongs to a small domain of frequency, from 0 Hz to 100 Hz. The
      range of frequency is similar for the two types of prostheses. CONCLUSION: Even
      though polyethylene is characterized by a more pronounced damping capacity than
      metallic materials, in experimental conditions simulating the vibratory
      characteristics of the human body, the introduction of a high-density
      polyethylene liner does not afford any additional shock-absorbing effect compared
      with a metallic head. It cannot explain cartilaginous sparing.

PMID- 11319428
TI  - [New varieties of lateral metatarsophalangeal dislocations of the great toe].
AB  - PURPOSE OF THE STUDY: We report seven cases of traumatic dislocation of the great
      toe, detailing the anatomy, the mechanism of injury and the radiographic
      diagnosis. We propose an additional classification based on three hereto
      unreported cases. MATERIAL AND METHODS: Between october 1994 and october 1997, we
      treated seven patients with traumatic dislocation of the first metatarso
      phalangeal joint of the great toe. There were six men and one woman, mean age 35
      years (range 24 - 44 years). Dislocation was caused by motor vehicle accidents in
      four cases and by falls in three. Diagnosis was made on anteroposterior, lateral
      and medial oblique radiographs. According to Jahss' classification, there was one
      type I and three type IIB dislocations. There was also one open lateral
      dislocation and two dorsomedial dislocations. Only these dorsomedial dislocations
      required open reduction, done via a dorsal approach. Mean follow-up was 17.5
      months (range 9 - 24 months) in six cases. One patient was lost to follow-up. The
      outcome was good in six cases and poor in one (dorsomedial dislocation).
      DISCUSSION: Dislocation of the first metatarso-phalangeal joint of the great toe
      is an uncommon injury. In 1980, Jahss reported two cases and reviewed three
      others described in the literature. He proposed three types of dislocation based
      on the feasibility of closed reduction (type I, II and IIB). In 1991, Copeland
      and Kanat reported a unique case in which there was an association of IIA and IIB
      lesions. They proposed an addition to the classification (type IIC). In 1994,
      Garcia Mata et al. reported another case which had not been described by Jahss
      and proposed another addition. All dislocations reported to date have been
      sagittal dislocations. Pathological alteration of the collateral ligaments has
      not been previously reported. In our experience, we have seen one case of open
      lateral dislocation due, at surgical exploration, to medial ligament rupture and
      two cases of dorsomedial dislocation due, at surgical exploration, to lateral
      ligament rupture. CONCLUSION: We propose another additional classification with
      pure lateral dislocation (type III) and dorso-lateral dislocation (type IL or
      IIL+), which are related to the formerly described variants.

PMID- 11319429
TI  - [Beta risk: an unrecognized risk of statistical error].
AB  - Data collected in a medical study should, from a methodological point of view, be
      considered as a sample taken from a larger population. The purpose of the
      statistical analysis is to check whether the differences in the experimental
      results observed in different subgroups are related to chance or not. The risks
      of error must be known to assess the validity of the conclusions. The first order
      risk, also called the alpha risk, is the risk of announcing a wrongly positive
      conclusion, that is to conclude that there is a significant difference that in
      reality does not exist. By convention, an alpha risk of 5 p. 100 is generally
      accepted. This means that it is acceptable to announce a statistically positive
      test when no difference exists in at most 5 p. 100 of the cases. After recording
      and processing the data, the statistical analysis produces a value called p that
      is the exact value of the first order risk in the given situation. If p is less
      than or equal to the alpha risk accepted before the study, it can be concluded
      that the observed difference is statistically significant at the chosen alpha
      level and that the p value represents the risk of first order risk in the given
      situation. If p is greater than the initially accepted alpha, the observed
      difference is not considered to be significant at the alpha level. But the
      assertion that two samples are equivalent, also involves a second order risk,
      also called the beta risk, that must be known. The beta risk is the risk of
      announcing wrongly negative results, that is to conclude that two samples are
      equivalent while in reality they are different. The number of elements in each
      sample necessary to demonstrate a difference becomes greater as the size of the
      difference becomes smaller. The beta risk increases as the alpha risk decreases,
      the number of cases becomes smaller, and the difference to detect becomes
      smaller. If a difference is not statistically significant at the chosen alpha
      level, the beta risk of an erroneous conclusion of equivalence is generally less
      than or equal to 20 p. 100. In most cases, the beta risk is not determined before
      the study but after, being calculated from the alpha risk, the sample size, and
      the non-significant difference observed. If the beta risk is found to be greater
      than 20 p. 100, no conclusion can be drawn and the study data are useless. It is
      therefore preferable to define both the alpha and beta risk and the smallest
      clinically pertinent difference, and to calculate the necessary sample size,
      before initiating the study. Let us take a numerical example where two different
      treatments, A and B, are given to two groups of 100 patients each. Treatment A
      produced success in 70 cases and treatment B in 80 cases. The chi-squared test
      yields a p value of 0.10. The observed difference is thus not statistically
      significant at an alpha level of 5 p. 100. In this case, the calculated beta risk
      is 54 p. 100. With 200 patients and a beta risk of 20 p. 100, a difference of 20
      p. 100 in the success rates between the two groups cannot be detected. If it is
      accepted that a difference of 10 p. 100 between the success rates is clinically
      pertinent, to have an acceptable beta risk of 20 p. 100 and detect the
      difference, the study would have to include 500 patients instead of 200. In
      conclusion, when a comparative study concludes that there is no significant
      difference between two groups, one cannot deduct that these two groups are
      identical unless the beta risk is less than 20 p. 100. If the beta risk is
      greater than 20 p. 100, or if it is not mentioned, one cannot conclude that the
      two groups are equivalent.

PMID- 11319430
TI  - [Comminutive fracture of the trapezium treated by ligamentotaxis. A case report].
AB  - We report a case of trapezium fracture treated by continuous traction. The
      fracture involved the trapezium alone and was associated with scapho-trapezium
      subluxation. Three percutaneously inserted pins were used for traction, one
      scapho-capitate pin and two pins in the first and second metacarpal bones. This
      allowed distraction of the entire first row. Good anatomic reconstruction of the
      trapezium was evidenced radiographically. The functional outcome was quite
      satisfactory with mobility strictly the same as the healthy side and complete
      pain relief.

PMID- 11319431
TI  - [Rare localizations of bone tuberculosis. Three case reports].
AB  - Bone and joint involvement is observed in 3 to 5 p. 100 of all cases of
      tuberculosis and in 15 p. 100 of extrapulmonary tuberculosis. Spinal and weight
      bearing joints are most frequently involved. We report three cases of bone
      tuberculosis with rare localizations that raised difficult diagnostic problems.
      Our patients had tuberculosis of the sternum, the iliac bone and in the third
      case, the spine but solely in the posterior arch of the fourth cervical vertebra.
      X-ray evidenced bone lysis and invasion of adjacent tissues. The cold abscesses
      were evacuated surgically allowing bacteriological and histological diagnosis.
      The patients were successfully treated with anti-tuberculosis regimens. An
      infectious etiology should be considered in patients with bone lesions in order
      to obtain the samples necessary for positive diagnosis.

PMID- 11319432
TI  - [Infection of a total knee prosthesis revealed by an abscess of the posterior leg
      compartment. A case report].
AB  - We report a case of infection of a non-cemented total knee prosthesis that led to
      abscess formation in the posterior compartment of the leg. This case illustrates
      the deleterious effect of screws used to fix the non-cemented articular surface
      of the tibia. Infection, like osteolysis due to polyethylene granuloma, can
      develop along the screw tract and reach the posterior compartment, especially
      when the screw protrudes through the posterior cortical of the tibia. Diffusion
      of an intra-articular event into the posterior compartment should be suspected in
      patients with a total knee prosthesis who experience calf pain.

PMID- 11319433
TI  - [Original valgus tibial osteotomy by internal opening and without loss of bone
      contact. Technique and incidence of consolidation speed: a preliminary series of
      33 cases].
AB  - PURPOSE OF THE STUDY: We propose an original open wedge medial osteotomy of the
      upper tibia. This new technique, unlike conventional open wedge osteotomies,
      allows a large bone contact surface without requiring graft filling. MATERIAL AND
      METHOD: The new technique is based on two anterior and posterior hemi-osteotomies
      instead of the single osteotomy with the classical technique. The two hemi
      osteotomies join laterally but start medially at very different heights on the
      tibia. The two hemi-osteotomies open a wedge but nevertheless lead to a very
      large bone contact due to the slippage in a frontal connecting frontal osteotomy.
      The technique uses a cutting guide to allow perfect orientation meeting the
      requirements of the operative plan. We studied prospectively the first 33
      patients who underwent this new procedure in two centers (Jouvenet Clinic and
      Tenon Hospital, Paris). We report here the effect on healing time. RESULTS: There
      was one failure (retarded healing and partial loss of correction) due to
      incomprehension of the postoperative instructions. The other 32 cases
      consolidated in 45 days. No graft filling was needed.

PMID- 11319434
TI  - ["Simultaneous knee arthroplasty and tibial osteotomy, for knee osteoarthritis
      and severe congenital genu varum deformity"].

PMID- 11319435
TI  - [Establishing quality-assurance for invasive procedures].

PMID- 11319436
TI  - [Patients with alcoholic liver disease hospitalized in gastroenterology. A
      national multicenter study].
AB  - OBJECTIVES: To describe the characteristics of in-patients with alcoholic liver
      disease in Hepatogastroenterology and to evaluate whether geographic location was
      a risk factor for cirrhosis. METHODS: A French, national, multicenter,
      prospective investigation was performed in the last quarter of 1997. To be
      included in the study, patients had to have drunk at least 50 g of alcohol per
      day for the past year or to have cirrhosis. RESULTS: Seventeen centers included
      802 patients, 20% had histologically proven cirrhosis or probable cirrhosis.
      Thirty-five percent had undergone liver biopsy. Twenty five percent of these
      patients had cirrhosis without acute alcoholic hepatitis and 37% had cirrhosis
      with acute alcoholic hepatitis. After dividing France along a Bordeaux-Strasbourg
      axis, there was more histologically proven or probable cirrhosis in the North
      (46%) than in the South (36%) (P<0.005) while daily alcohol intake was greater
      the South (150 +/- 6 g) than in the North (129 +/- 4 g) (P<0.0001). When the six
      variables (age, sex, daily consumption of alcohol over the past 5 years, presence
      of hepatitis B surface antigen and antibodies to hepatitis C virus, total
      duration of alcohol abuse) were considered together in stepwise logistic
      regression analysis, geographic location changed the prediction of cirrhosis. The
      odds ratio for cirrhosis in patients living to the North of the Bordeaux
      Strasbourg axis was 1.9 (95% confidence interval range 1.1-3.2) (P<0.02),
      suggesting the role of nutritional factors.

PMID- 11319437
TI  - [Mechanisms of the inflammatory reaction implicated in acute experimental
      alcoholic hepatitis].

PMID- 11319438
TI  - [How to evaluate the results of functional proctologic surgery?].

PMID- 11319439
TI  - [Can common bile duct lithiasis be removed laparoscopically without external
      biliary drainage?].
AB  - AIM OF THE STUDY: To evaluate the indications, feasibility and results of
      laparoscopic treatment of common bile duct stones without biliary drainage.
      PATIENTS AND METHODS: Between 1992 and 1999, laparoscopic procedures were
      performed in 70 consecutive patients, mean age 60 +/- 15 years (range: 18-82).
      Stone removal was attempted via the cystic duct (n=25) or choledocotomy (n=45).
      The emptiness of the common bile duct was checked by intraoperative
      cholangiography or endoscopy. After choledocotomy, closure was performed by
      interrupted or non-interrupted suture with slowly resorbable thread. Transcystic
      drainage was used whenever necessary. RESULTS: Nine conversions to laparotomy
      were necessary (12.8%). Among the 61 patients who had an exclusively laparoscopic
      procedure, 21 were treated via the transcystic route and 40 through
      choledocotomy. Biliary endoscopy was possible in only 10 of the 21 patients
      (47.6%) treated via the transcystic route and in all with choledocotomy. No
      biliary drainage was used in 16 of the 21 patients treated via the transcystic
      route and in 39 of the 40 treated through choledocotomy. The 30-day mortality was
      1/61 (1.6%). Morbidity was 9.8% and 2 patients underwent a second laparoscopic
      procedure (one fistula on a choledocotomy suture, one hemoperitoneum of unknown
      origin). An endoscopic sphincterotomy for residual stone was necessary in 4
      patients (4/61, 6.5%), 2 after choledocotomy for an unrecognized stone without
      biliary drainage. CONCLUSIONS: These results confirm the feasibility of
      laparoscopic treatment of common bile duct stones and suggest it can be performed
      without biliary drainage in most cases.

PMID- 11319440
TI  - [Quality of life, symptoms of dyschezia, and anatomy after correction of rectal
      motility disorder].
AB  - AIM OF THE STUDY: To evaluate the quality of life of patients suffering from
      dyschezia and its correlation with symptomatic complaints and anatomical
      abnormalities, before and after elective surgery for rectal static disorder.
      PATIENTS AND METHODS: A prospective study was conducted using a general quality
      of life questionnaire (SF36) and a constipation specific score (PAC-QoL), a
      dyschezia symptom score, and defecography. RESULTS: Thirty-eight female dyschesic
      patients (mean age 54 years) underwent surgery for rectocele with (n=16) or
      without (n=14) internal rectal prolapse, an isolated internal rectal prolapse
      (n=3), or a total rectal prolapse (n=5). Preoperative quality of life was low,
      correlated with the intensity of dyschezia. Seven months after surgery, quality
      of life and dyschezia improved independently of the amplitude of the anatomical
      correction. More items improved in the constipation specific score than on the
      quality of life questionnaire; they were correlated with the course of dyschezia
      symptoms. Neither incontinence nor irritable bowel syndrome affected evolution of
      the symptoms. CONCLUSION: Surgery improved initially low quality of life and
      symptomatic complaints in patients with dyschezia and a rectal static disorder,
      independently of anatomic repair. Differences in changes observed in the PAC-QoL
      and SF36 suggest different fields of application.

PMID- 11319442
TI  - [Acute pancreatitis: new physiopathological concepts].

PMID- 11319441
TI  - [Is endoscopic diagnosis of Candida albicans esophagitis reliable? Correlations
      with pathology and mycology].
AB  - AIM OF STUDY: To assess the reliability of endoscopic diagnosis of Candida
      albicans esophagitis. PATIENTS AND METHODS: A case - control prospective study
      was carried out from November 1997 to July 1998 at the Campus Teaching Hospital
      of Lome, in patients with esophagitis macroscopically suggestive of Candida
      albicans origin at upper digestive endoscopy. Fifteen subjects with normal
      endoscopy served as controls. Esophageal biopsies for mycologic and pathological
      examination were performed, as well as HIV serology. RESULTS: During the study
      period, 26 of the 850 endoscopies performed in our Unit revealed an esophagitis
      suggestive of Candida albicans origin. Mycology confirmed the presence of
      filamentous form of Candida albicans in 23 patients and pathology showed non
      specific lesions of esophagitis, 20 with intramucous hyphae. HIV serology was
      positive in 19/23 patients (82.6%) and in 1/15 controls (6.6%). Sensitivity and
      specificity of upper GI endoscopy for the diagnosis of Candida albicans were 100
      and 83.3% respectively; positive and negative predictive values were 88.5 and
      100%, respectively. CONCLUSION: Upper digestive endoscopy is a reliable method
      for the diagnosis of Candida albicans esophagitis. However, mycological
      confirmation is warranted.

PMID- 11319443
TI  - [Consensus conference: acute pancreatitis].

PMID- 11319444
TI  - [Hepatic disorders related to Lyme disease. Study of two cases and a review of
      the literature].
AB  - We report two cases of Lyme disease, revealed by hepatic damage in a 71- and a 59
      year old man. In the first case, the disease was revealed by febrile jaundice
      whereas, in the second case, results of liver tests showed cytolytic and
      cholestatic abnormalities with fever. Lyme disease is a zoonosis due to infection
      by Borrelia burdorferi transmitted by ticks. The multiple phases of the disease
      explain the polymorphism of the clinical manifestations. Usually, extrahepatic
      symptoms are first observed, including neurological tropisms of Borrelia
      burdorferi. On the contrary, hepatic impairment due to Lyme disease is rare,
      often asymptomatic and with biological manifestations only.

PMID- 11319445
TI  - [Ulceronecrotic tracheobronchial involvement in Crohn's disease].
AB  - We report the case of a young female patient hospitalized for the first episode
      of a colonic Crohn's disease with specific ulceronecrotic tracheobronchial
      involvement leading to chronic and invalidant cough. Symptomatic bronchopulmonary
      manifestations are very rare in the course of inflammatory bowel diseases and
      usually not mentioned in Gastroenterology textbooks.

PMID- 11319446
TI  - [Non-alcoholic steatohepatitis with cirrhosis after raltitrexed administration].

PMID- 11319447
TI  - [Acute cholestatic hepatitis due to chlorambucil].

PMID- 11319448
TI  - [Palmar fasciitis and paraneoplastic polyarthritis associated with hepatocellular
      carcinoma].

PMID- 11319449
TI  - [Adenocarcinoma of the esophago-gastric junction arising after endoscopic laser
      photocoagulation ablation of the short segment of Barrett's esophagus].

PMID- 11319450
TI  - [Readministration of oxaliplatin using a rapid desensitization method after
      severe anaphylactic reaction].

PMID- 11319451
TI  - [Adenocarcinoma of the common bile duct and celiac disease].

PMID- 11319452
TI  - [Primary hyperparathyroidism associated with colon cancer].

PMID- 11319453
TI  - [The precautionary principle: to be used with precaution].

PMID- 11319454
TI  - [The precautionary principle: advantages and risks].
AB  - The extension of the precautionary principle to the field of healthcare is the
      social response to two demands of the population: improved health safety and the
      inclusion of an informed public in the decision-making process. The necessary
      balance between cost (treatment-induced risk) and benefit (therapeutic effect)
      underlies all healthcare decisions. An underestimation or an overestimation of
      cost, i.e. risk, is equally harmful in public healthcare. A vaccination should be
      prescribed when its beneficial effect outweighs its inevitable risk. Mandatory
      vaccination, such as in the case of the Hepatitis B virus, is a health policy
      requiring some courage because those who benefit will never be aware of its
      positive effect while those who are victims of the risk could resort to
      litigation. Defense against such accusations requires an accurate assessment of
      risk and benefit, which underlines the importance of expertise. Even within the
      framework of the precautionary principle, it is impossible to act without
      knowledge, or at least a plausible estimation, of expected effects. Recent
      affairs (blood contamination, transmissible spongiform encephalitis by growth
      hormone, and new variant of Creutzfeldt-Jacob disease) illustrate that in such
      cases the precautionary principle would have had limited impact and it is only
      when enough knowledge was available that effective action could be taken.
      Likewise, in current debates concerning the possible risks of electromagnetic
      fields, cellular phones and radon, research efforts must be given priority. The
      general public understands intuitively the concept of cost and benefit. For
      example, the possible health risks of oral contraceptives and hormone replacement
      therapy were not ignored, but the public has judged that their advantages justify
      the risk. Estimating risk and benefit and finding a balance between risk and
      preventive measures could help avoid the main drawbacks of the precautionary
      principle, i.e. inaction and refusal of innovation, highly restrictive
      administrative procedures, and a waste of funds on the search for the utopian
      goal of zero risk. Other drawbacks are more insidious. The precautionary
      principle could contribute to a general feeling of anxiety and unease in the
      population. It could be used by campaigns to manipulate public opinion in favor
      of a particular commercial interest or ideology. Furthermore, practitioners and
      public policy makers could be led to make choices not dictated by a search for
      the optimal solution but rather a solution that would protect them from future
      accusations (the so-called umbrella phenomenon). On the international level, the
      precautionary principle must not be used to mask protectionism. Nevertheless, a
      clear advantage of the precautionary principle is that it requires decision
      makers to explain the rationale behind their decisions, to quantify the risks,
      and to provide objective information. However, the physician must not be tempted
      to make patients sign documents certifying that they have been given all relevant
      information on his or her diagnosis and treatment. This example underlines the
      role of legal texts and jurisprudence in the application of the precautionary
      principle. Finally, the precautionary principle implies new obligations for the
      State. In the field of health and healthcare, the State must undertake actions
      based on fully open and undisguised decision-making and provide complete
      information to the public. A pplication of the precautionary principle requires
      much discernment because the final outcome can be beneficial or harmful,
      depending on the way it is implemented. The precautionary principle, and its
      applications, must be precise and detailed within a well-defined framework.

PMID- 11319455
TI  - [Radiofrequency for the treatment of liver tumors].
AB  - Radiofrequency is performed with thin electrodes that are placed in the center of
      a tumor under ultrasonographic guidance. Radiofrequency waves induce ionic
      agitation which destroys neighboring tissues by heat. The most recent equipment
      can produce necrosis of 4-cm diameter areas. Efficacy is enhanced by blocking
      intrahepatic blood flow which naturally refreshes the liver parenchyma. The
      technique has the advantage of minimal invasion and of sparing liver parenchymal
      tissue. radiofrequency can be performed percutaneously or by laparoscopi or
      laparotomy. results in most reported series have been good with low morbidity.
      rapid improvment of material and of new associated procedures (vascular clamping,
      cooling infusion of the bile ducts, transplaeurodiaphragmatic approach,
      combination with other new approaches in liver surgery) are continuously
      modifying performance levels and potential indications curently under validation.
      radiofrequency, like other tools for local tumor destruction, will greatly change
      our therapeutic strategies in the neat future.

PMID- 11319456
TI  - [Laparoscopic resection of the right adrenal gland].

PMID- 11319457
TI  - [Simplified vaginal hysterectomy].

PMID- 11319458
TI  - [Terminalized functional lateral ileostomy].

PMID- 11319459
TI  - [Abdominal fibromatosis (desmoid tumor)].

PMID- 11319460
TI  - [Gastrointestinal stromal tumors].
AB  - There are two main types of gastrointestinal connective tissue tumors:
      differentiated connective tissue tumors arising from smooth muscle tissue,
      schwanommas or fibroblastic tissue, and non-differentiated connective tissue
      tumors with no precise origin. Pathologically non-classifiable tumors comprise a
      group of real gastrointestinal stromal tumors. Stromal tumors are rare and
      generally develop in the stomach. Immunohistochemistry has been able to identify
      three entities: stromal tumorswith skenoid fibers, gastoinestinal autonomic nerve
      tumors, and intraabdominal desmoplastic small round-cell tumors. After resection,
      survival is almost 50% at 5 years and depends particulary on tumors size, the
      presence of synchronous metastases and mitosis count.

PMID- 11319461
TI  - [A 48-year-old woman admitted for an occlusive syndrome and jaundice with
      elevated liver enzymes].

PMID- 11319462
TI  - [About Pierre Jourdan].

PMID- 11319463
TI  - [Resuscitation in severe forms of pre-eclampsia (short text)].
AB  - An expert's conference about Intensive Care in preeclampsia was organized by the
      French Society of Anesthesiology and Intensive Care (SFAR) associated with the
      societies of Pediatrics (SFP) and Obstetricians (SFMP and CNGOF). Each expert
      wrote a chapter according to instructions previously defined by the Referential
      Committee of Sfar. The coordinator was in charge of a short text which was
      presented to each society. The main issue was the intensive care management, but
      chapters about epidemiology, pathology and physiopathology were also included.
      Principles of care in less severe cases were also added as well as prognosis in
      mothers and babies. Finally, mandatory anesthetic requirements of were also
      presented. The aim of this work was to take stock of the state of art in severe
      preeclampsia. Due to improved knowledge, intensive care strategies for severe pre
      eclampsia will have to be updated in the near future.

PMID- 11319464
TI  - [Withholding and withdrawing treatment in the perinatal period: importance of a
      coherent attitude between gyneco-obstetricians and pediatricians].
AB  - According to several recent surveys, 50% of deaths occurring in neonatal
      intensive care units in France occur subsequent to a medical decision. The French
      Neonatal Group therefore decided to publish guidelines for practice. These
      guidelines present: definitions, clinical situations, ethical principles,
      obligations of the medical and nursing staff, and specific conditions where
      dilemmas occur. These guidelines focus on the obstetrico-pediatrics relationship.

PMID- 11319465
TI  - [Laparoscopic promontofixation feasibility study in 44 patients].
AB  - OBJECTIVE: To evaluate the feasibility of laparoscopic promontofixation.
      MATERIAL: and methods. Forty patients between 1993 and 1999 were scheduled for a
      laparoscopic promontofixation. Fifteen of these patientes had a previous cure of
      prolapse with recurrence. Three patients had a "universal jointcervix" syndrome
      (Masters and Allen). RESULTS: We observed no recurrence of the prolapse after an
      average follow-up of 18.6 months. The peroperatoire complication rate is 9%, and
      the postoperative complication rate is 9% too. 4.5% of the patients had to
      undergo a laparotomy. CONCLUSION: Laparoscopic promontofixation is feasible with
      good results in the cure of genital prolapse. Laparoscopy is performing the same
      procedure as the open technique with the advantages of the minimal invasive
      surgery.

PMID- 11319466
TI  - [Surgical treatment of stress incontinence using a new vaginal tissue sling:
      short-term feasibility and complications].
AB  - OBJECTIVE: Many operative techniques have been proposed for urinary stress
      incontinence, a common finding in women. The goal of operating solely via a
      vaginal approach using autologous material has led to the development of a sling
      technique using a band of vaginal tissue. METHODS: We described the operative
      technique and analyzed outcome in the first 35 patients operated with the new
      vaginal tissue sling technique. RESULTS: Mean duration of the procedure was 35
      minutes. The procedure was performed in two cases and thus could be used for
      prolapsus cure. We had no peroperative complications. Postoperative complications
      were mainly urine retention (50%) lasting a mean 4.4 days. Transfixation of the
      bladder was observed late in one case with resection of an intravesicular suture.
      At mean follow-up of 16.9 months, the success rate was 80% with 68.5% of the
      patients free of urine leakage. In case of sphincter insufficiency, the success
      rate was 85.7% (64.3% of the patients were free of leakage). Three of the four
      patients who had undergone prior Burch colpopexy were cured. DISCUSSION: Our
      series demonstrated the feasibility of the new vaginal tissue sling technique. It
      appears to be an adapted procedure for urinary stress incontinence with sphincter
      insufficiency and particularly well adapted for low closure pressures and after
      failure of surgical cure. The final assessment of this technique will require
      longer follow-up and comparative studies with other methods.

PMID- 11319467
TI  - [Hysterectomy for benign lesions in the north of France: epidemiology and
      postoperative events].
AB  - OBJECTIVE: We conducted an inquiry on hysterectomy practices in gynecology and
      obstetric units of general hospitals in the north of France (North and Picardy
      regions) focusing on procedures made for benign lesions of non-prolapsed uteri.
      MATERIAL: and methods: Two studies supported this inquiry. The first was a
      retrospective study in 1997 concerning 21 gynecology and obstetric units in
      general hospitals among the 24 units belonging to the general hospital network in
      the North and Picardy regions. The series included 1293 hysterectomies for benign
      lesions on non-prolapsed uteri, accounting for 68.6% of all hysterectomies
      performed during the study period. Surgical route, indications and duration of
      hospital stay were recorded. The second study was a prospective study conducted
      in 1998 in 9 voluntary units among the 24 units in the hospital network. This
      study included 423 hysterectomies and recorded techniques, indications, and
      complications as well as late complications and social and psycho-sexual impact
      assessed during a telephone interview at 3 months. The 5 University Hospitals in
      the North, Picardy and Champagne regions also participated in the inquiry and
      provided data on 191 hysterectomies performed during a three-month period.
      RESULTS: Twenty-seven hysterectomies were performed per year and per operator.
      The main indications for hysterectomy were, for the two studies respectively:
      fibroid uterus 66.7% and 60%, menstrual disorders 13.8% and 27.2%, endometriosis
      10.6% and 5%, and hyperplasia of the endometrium 3.9% and 5%. Surgical routes
      recorded in the second study were: vaginal 64.8%, abdominal 30.5%, vaginal
      laparoscopy 4.7%. Reductions were performed to facilitate vaginal hysterectomy in
      25% of the cases. The vaginal route was used for adnexectomy in 30% of the cases.
      The rate of peroperative complications were observed in 3 - 4.8% of the vaginal,
      4.8 - 10.7% of the abdominal and 15% of the laparoscopic vaginal hysterectomies.
      Bleeding was reported in 0.4% and 9.3% of the vaginal and abdominal
      hysterectomies respectively (p<0.001). The rate of postoperative complications
      was 0.8 - 4.9%, 1.6 - 19.4%, and 5% for vaginal, abdominal and vaginal
      laparoscopic hysterectomies respectively. Duration of convalescence was 4.4 weeks
      for vaginal and 6.1 weeks for abdominal (p<0.00001) and 5.3 weeks for vaginal
      laparoscopic procedures. The quality of sexual intercourse was improved in 30% of
      the patients irrespective of the surgical rout but was found to be deteriorated
      in 20% of those who had laparoscopic vaginal hysterectomy. DISCUSSION: It is
      difficult to ascertain the exact number of hysterectomies performed in France.
      The computerized information system currently in use in France (PMSI) should
      provide interesting data. Reports from North America, Great Britain and the
      Scandinavian countries have found comparable data. Complication rate, duration of
      hospitalization and social impact are in favor of vaginal hysterectomy.

PMID- 11319468
TI  - [Sickle cell anemia and pregnancy: considerations on systematic prophylactic
      transfusion].
AB  - Sickle cell anemia, a congenital hemolytic type of anemia due to a genetic defect
      in the beta chain of the globin molecule can cause severe disease. During
      pregnancy, the risk for preeclampsia and deep venous thrombosis is increased in
      patients with sickle cell anemia. Occlusion of placenta blood vessels with rigid
      deformed erythrocytes can cause repeated miscarriages and intra-uterine fetal
      death. Repeated blood transfusions can prevent these complications by reducing
      the concentration of abnormal hemoglobin S. We report on the evolution of five
      pregnancies in three patients with sickle cell anemia who received multiple blood
      transfusions during gestation, and discuss advantages and risks involved in the
      care of such cases.

PMID- 11319469
TI  - [An appreciation of maternal smoking with high-performance liquid chromatographic
      determination of maternal and neonatal urinary cotinine].
AB  - OBJECTIVE: To study the correlation of urinary cotinine levels in mothers and
      newborns with the number of cigarettes smoked at the end of pregnancy. Population
      and methods. We recorded the smoking habits of 123 mothers attending a university
      maternity clinic and measured urinary cotitine levels in mothers and their
      newborns. All mothers were Europeans and gave birth to a normal full-term (37
      weeks gestation) infant. Cotinine levels were measured with high-performance
      liquid chromatography from urine samples taken during the 6-hour period prior to
      or after delivery for the mothers and 24-h after birth for the newborns. RESULTS:
      The average cotinine level for non-smoking mothers, for those who smoked one to
      nine cigarettes a day and heavy smokers (ten or more cigarettes per day) were
      0.21, 2.17 and 4.28 mol/l respectively (p<0.001). The average levels in their
      newborns were 0.04, 0.39 and 1.36 mol/l respectively (p<0.001). Thirteen percent
      of the mothers who claimed they did not smoke had cotinine levels higher than the
      significance cut-off (0.3 mol/l). There was a significant correlation 1) between
      the number of cigarettes the mothers stated they smoked at the end of pregnancy
      and their urinary cotinine concentrations (cotinine level=0.213 + 0.349
      cigarettes, r=0.78, p<0.001); 2) between the number of cigarettes smoked and
      newborn's urinary cotinine concentration (cotinine level=0.002 + 0.104
      cigarettes/day, r=0.81, p<0.001); and 3) between the mother's and the newborn's
      urinary cotinine concentrations (newborn cotinine=0.027 + 0.219 maternal
      cotinine, r=0.77, p<0.001). CONCLUSION: The number of cigarettes smoked at the
      end of pregnancy accounts for roughly 50% of the variance in the mother's urinary
      cotinine level and that in her newborn at birth. The urinary cotinine
      concentration in newborns is 3 to 5 times lower than that of their mothers. A
      woman smoking 3 cigarettes per day has a urinary cotinine concentration of 1
      mol/l. The urinary cotinine level in newborns is 1 mol/l for mothers smoking 10
      cigarettes per day.

PMID- 11319470
TI  - [Factors predicting outcome of trial of labor after prior cesarean section in a
      developing country].
AB  - OBJECTIVE: To determine factors predictive of the outcome of trial of labor after
      cesarean section in women living in developing countries. MATERIAL: and methods.
      A retrospective study of 313 cases of trial of labor was conducted in patients
      with a history of at least one prior cesarean section. Multiple logistic
      regression was used to identify predictive factors. The adjusted odds ratios with
      95% confidence intervals (95%CI) were used to indicate risk of failure of the
      trial of labor when the factor was present. RESULTS: The rate of vaginal birth
      was 71.6%. Factors significantly predictive of failure of trial of labor were
      birth weight>3000 g (OR=2.68; 95%CI: 1.57-4.57), no previous vaginal delivery
      (OR=1.71; 95%CI: 1.26-3.76) and maternal age>28 years (OR=1.71; 95%CI: 1.01
      2.90). CONCLUSION: Trial of labor should be proposed in most women with one
      previous cesarean section. A prior history of vaginal delivery is the best
      predictor of the positive outcome of trial of labor.

PMID- 11319471
TI  - [Cystic adenoid carcinoma of the endocervix (or cylindroma of the uterine
      cervix). Exclusive laparoscopic vaginal treatment].
AB  - We report a rare case of adenoid carcinoma of the endocervix (cylindroma).
      Laparoscopic lymphadenectomy and extended vaginal hysterectomy (Schauta-Dargent
      operation) was successfully performed. We present illustrative pathology findings
      and review the literature on this severe disease.

PMID- 11319473
TI  - [Breach presentation: questions raised by the controlled trial by Hannah et al.
      on systematic use of cesarean section for breach presentations].

PMID- 11319472
TI  - [Multidisciplinary management of aortic dissection complicating pregnancy].
AB  - BACKGROUND: Most cases of aortic dissection observed in women under 40 years of
      age occur as a complication of pregnancy in patients with other risk factors.
      Case report. We report a case of dissection of the ascending aorta in a young
      primigravida at 35 weeks gestation. The risk factor was aortic regurgitation.
      Multidisciplinary management enabled fetal extraction followed by repair of the
      aorta. Outcome was favorable for both mother and child. DISCUSSION: A review of
      the literature shows a variety of etiological factors leading to this disease.
      Emergency diagnosis and management is mandatory. Obstetricians should be aware
      that pregnancy can be a triggering factor in patients with a predisposition, e.g.
      connective tissue disease. A complete cardiovascular evaluation should be
      conducted before conception and a suitable surveillance planned for the entire
      pregnancy. The aim of this careful follow-up it to avoid surgery in an emergency
      setting that could compromise prognosis for both mother and child.

PMID- 11319474
TI  - [The debate on breach presentation: Delivery of breach presentations: the
      position of the National College of French gynecologists].

PMID- 11319475
TI  - ["Labor trial" for breach presentation].

PMID- 11319476
TI  - [The question of breach presentation delivery, the answer lies up front].

PMID- 11319477
TI  - [Assessment of health care quality: a public health challenge].

PMID- 11319478
TI  - [Prevalence and incidence of HIV-1 infection among employees of a large textile
      business and their wives in Kinshasa, 1991-1996].
AB  - BACKGROUND: The Democratic Republic of Congo has been experiencing a critical
      economic situation for several years, resulting in a favorable context for the
      spread of HIV-infection. A study was performed in a large textile factory in
      Kinshasa, to determine prevalence and incidence of HIV-infection among employees
      and their wives. METHODS: From February to November 1996, a cross-sectional study
      was conducted among 2010 employees (1859 males, 151 females) of the factory and
      their 1198 female partners. Participants responded to a structured questionnaire
      and HIV testing was performed after an informed consent was obtained in a pre
      test counselling session. Using a reconstituted population of 1580 employees
      (1502 males, 78 females) and their 806 female partners (all HIV-seronegative in
      1990), we determined the HIV incidence between 1990 and 1996. Employees included
      manual workers, middle managers and senior managers. RESULTS: Overall prevalence
      and incidence rates were 2.1% (95% CI=1.6%-2.6%) and 0.16/100 persons-years (95%
      CI=0.09-0.22) respectively. Reported condom use was associated with HIV infection
      in men (OR=2.5; 95% CI=1.2-5.3) and their spouces (OR=1; 95% CI=0.02-10.7) and
      with a history of urethral discharge in men (OR=4.1; 95% CI=1-30.1). The HIV
      incidence between 1990 and 1996 was 0,2/100 person-years (95% CI=0.1-0.2). The
      seroconversion risk increased from manual workers to senior managers (chi-square
      for linear trend=12.9; p<0.001). CONCLUSIONS: Despite the deterioration of health
      services and the economical instability in Kinshasa, HIV prevalence and incidence
      rates in this factory were much lower than rates observed in factories in same
      East and Southern African countries. Comparative prospective studies using a
      similar methodology are needed to better understand the reasons for these
      differences.

PMID- 11319479
TI  - [Frequency of childhood injuries: first results of the Boulogne-Billancourt
      registry].
AB  - BACKGROUND: Boulogne-Billancourt database is in France the only permanent and
      specific childhood injury surveillance system. Integrated in an safe community
      program designed by the World Health Organization (WHO), the aims of a local
      database are to provide precise information intended to implement prevention
      actions. METHOD: All children less than sixteen years old living in Boulogne
      Billancourt, victims of injuries occurring in that town, and requiring hospital
      care, are targeted. RESULTS: Two thousand five hundred and eighty accidents have
      been computed between 1(st) January 1998 and 31 December 1999, i.e. an average
      annual incidence of 79.7/1000 children. As in other similar databases, domestic
      accidents are prevalent in the average (40%), even though after five years old
      school injuries become the most frequent ones (36%). Falls are the main mechanism
      involved in injury at any age (44 to 54%). Distribution of other mechanisms
      varies with respect to age: foreign body prevalence is maximum between one and
      four (2.5%), struck-collisions (38%) between ten and fifteen years old. A
      significant increase of falls involving roller-skates or skateboards has been
      observed between 1998 and 1999 (3.8% versus 1.1%, p<0.001). Predominanting injury
      causes are contusions (38%), mainly head trauma (10%), open wounds (16%),
      fractures (10%), and sprains (6%). Two hundred and twenty four injuried children
      have been admitted in 1998, 205 in 1999, i.e. respectively 13.8/1000 and
      12.7/1000 children dwelling in Boulogne. Overall recurrence rate is 32%, reaching
      47% after eleven years old. A significant relationship has been observed between
      injury recurrence and problems related to education (odds ratio: 2.95; 95% CI:
      1.75-5.00), atypical parenting situation (odds ratio: 1.70; 95% CI: 1.20-2.30),
      and family discord (odds ratio: 1.62; 95% CI: 1.05-2.50). Household accidents are
      the most avoidable ones in parents'opinion. This is not the case for road-traffic
      accidents, given evidence of the lack of means of protection observed in bicycle
      injuries. CONCLUSION: In spite of methodological issues such as control of
      exhaustivity of data, or difficulties to maintain a long-term surveillance sytem,
      this project worth carrying on with regard to provided information and usefulness
      for prevention. Other similar community experiences should be implemented with
      the aim of setting up a national-wide surveillance system, based on an homogenous
      data collection.

PMID- 11319480
TI  - Sentinel monitoring of general community health during the 1998 World Football
      Cup.
AB  - BACKGROUND: Present knowledge of the consequences of mass gatherings for the
      health of the community is scant. Our objective was to determine the impact of
      the 1998 World Football Cup on general community health. METHODS: We set up an
      electronic sentinel disease surveillance, before, during and after the World
      Football Cup tournament held in France from June 10 to July 12, 1998. Medical
      activity, and the daily number of cases of communicable, environmental, and
      societal diseases relating to mass gatherings were surveyed. The incidence of the
      pathologies surveyed in real time during and after the World Cup versus the pre
      Cup reference period was the main outcome measure. Five sentinel networks
      participated, comprising 553 general practitioners, 60 hospital adult emergency
      departments, 19 private emergency community services, 4 community health centres,
      and the medical centre of the Paris airports. RESULTS: Throughout the 66-day
      study period, physicians reported 558,829 medical encounters via 21,532
      connections to the computer. Compared to the reference period, the level of
      medical activity reflected by the pathological items surveyed remained stable
      during the study period. CONCLUSION: The 1998 World Football Cup had no
      epidemiological impact on general community health, as observed by sentinel
      networks located downstream of the specific health services provided by the
      French authorities to ensure high standards of safety.

PMID- 11319482
TI  - Influenza vaccine in healthy preschool children.
AB  - BACKGROUND: Studies of influenza vaccination in healthy children have not
      definitely answered the question of their efficacy. METHODS: We have carried out
      a randomized trial in a well selected population of healthy preschool children in
      Sardinia, Italy. During October 1995, 344 children aged 1 to 6 years, were
      randomly assigned to receive influenza vaccine (n=177) or no treatment (n=167).
      Two doses of a trivalent subvirion vaccine, containing 15mg of highly purified
      surface antigens from the component strains A/Johannesburg/33/94-like,
      A/Singapore/6/86-like and B/ Beijing/184/ 93-like were administered. Follow-up
      data were collected from December 1, 1995 through April 30, 1996. RESULTS:
      Seroconversion was documented in 17 out of 17 children. No specific systemic
      symptoms or severe local reactions were observed after vaccination. Influenza
      like episodes, defined by the presence of fever and cough or sore throat that
      lasted at least 72 hours, occurred in 63 (37.7%) of unvaccinated children and in
      22 (12.4%) of vaccinated ones. The corresponding reduction in disease incidence
      was 67% (95% CI: 0.59-0.74). Three episodes of otitis were observed among
      children in the control group versus zero among vaccinated children (p=0.07).
      Mean duration of day care center absenteism was significantly reduced by
      vaccination (2.3 days in unvaccinated and 0.5 day in vaccinated children,
      p<0.001) CONCLUSIONS: Influenza vaccine is safe and effective in healthy
      preschool children. However the favourable implications of vaccination on disease
      rate in subsequent years have to be evaluated.

PMID- 11319481
TI  - [Dietary risk factors of nasopharyngeal carcinoma in the Setif area in Algeria].
AB  - BACKGROUND: The aim of our work was to identify risk factors specific to
      populations in our region for primary prevention of risk behaviors, particularly
      eating habits. METHODS: We conducted a case-control study on dietary factors of
      nasopharyngeal carcinoma in the Setif area in Algeria. The study included 72
      cases and 72 controls matched for age, sex and area of residence. The variables
      analyzed were identified by an anthropological study. RESULTS: Increased risk of
      disease was associated with consumption of traditionally preserved foods such as
      "harissa", pickled fruit and vegetables and dried and salted meat. These factors
      were commonly found in other endemic areas. Certain products appeared to be
      specific to the Setif area including dried and salted fat, especially after
      prolonged exposure. Rancid butter was related to a 4 to 7-fold increase in risk
      and use of pickling increased the risk of nasopharyngeal carcinoma 4 to 12-fold
      depending on the type of food. CONCLUSIONS: These data point to the need for
      biochemical analysis of food specimens to search for the carcinogenic agents and
      to the importance of an immediate information and education program on food
      habits for the populations living in this area.

PMID- 11319483
TI  - [Evaluation of nutrition instruction in a group of Senegalese students at the
      secondary level].
AB  - BACKGROUND: In Senegal, nutrition instruction was implanted in 1981 in the
      national curriculum of biology and has never been evaluated since. METHODS: The
      purpose of this study, was to evaluate the effect of a six weeks nutrition
      instruction program on improving nutrition knowledge and nutrition attitudes in
      an experimental group including 81 subjects aged 16.7+/-1.2 years and a control
      group including 80 subjects aged 15.7+/-1.3 years. These subjects came
      respectively from third and fourth grade. A questionnaire on knowledge and one on
      attitudes were administered to the experimental group, before and after the
      nutrition instruction, while the control group, who did not received any
      nutrition instruction, also answered the questionnaires. RESULTS: Results
      indicate that the adjusted mean knowledge posttest scores did not significantly
      increase in the experimental group compared to the control group. In addition,
      the adjusted mean attitude postscores of the boys and girls of the experimental
      group on the attitude scale "Nutrition affects health" were significantly higher
      from that of the control group. CONCLUSION: An evaluation of the nutrition
      curriculum and the teaching methods is suggested in order to improve the
      effectiveness of this nutrition program.

PMID- 11319484
TI  - [Relationship between in-hospital mortality rate and patient volume for total hip
      arthroplasty in the Rhone-Alpes public hospitals].
AB  - BACKGROUND: Comparisons between hospitals using surgical volume, among other
      criteria can be made using large hospital databases. A relationship between
      hospital volume and care results, particularly mortality, is assumed to justify
      the use of activity volume as a comparison criterion. We aimed to assess a
      relationship between hospital volume and mortality after total hip replacement
      using the data available in the French Diagnosis Related Groups (Programme de
      Medicalisation des Systemes d'Information, PMSI). We also searched for a
      threshold associated with mortality. METHODS: We included all stays with a
      surgical procedure for total hip replacement in public hospitals in the Rhone
      Alpes region in France in 1997 (n=5521). We examined the relationship between
      mortality and the number of procedures per hospital and assessed activity
      threshold using logistic regression. RESULTS: Using the number of procedures as
      the continuous variable, we observed a relationship with mortality (OR=0.94
      [0.91; 0.96] for an increase in activity of 100 total hip replacements). We found
      no evidence of an activity threshold. The reason for performing total hip
      replacement (OR=6.36 [2.78; 14.55] for trauma compared with rheumatology
      diseases) and patient age (OR=1.76 [1.31; 2.36] for a 10-year increase in age)
      were strongly related to mortality. CONCLUSIONS: PMSI only collects in-hospital
      mortality, limiting the impact of our findings. The relationship between
      mortality and hospital volume is significant, but too small and consequently of
      little use. We found no activity threshold. It would be difficult to recommend
      surgical volume as a criterion for comparing hospitals.

PMID- 11319485
TI  - [Early readmission as an indicator of hospital quality of care].
AB  - BACKGROUND: The purpose of this study was to assess early readmission as an
      indicator of quality of care, to estimate the frequency of avoidable emergency
      readmission in a French hospital, and then to describe the feasibility and
      contribution of routine use of this indicator. METHODS: A randomly selected
      sample of 469 readmissions within 30 days after a conventional hospitalization
      was chosen among the database of 40,242 hospitalizations during the first half of
      1997. Two independent practitioners, whose true agreement was measured with a
      kappa test, studied the features of readmission recorded on the patient files,
      classing them as "unforeseeable" or "potentially avoidable". Database criteria
      that could automatically class the readmission in either group were analyzed.
      RESULTS: There were 119 unforeseeable readmissions (25.4%). The two physicians
      agreed on the unforeseeable nature of 97 of these readmissions and 50 of them
      were judged avoidable. None of the database criteria allowed identifying all
      unforeseeable and avoidable readmissions. Readmission via the emergency unit was
      a sure indicator of unforeseeable readmission in 66% of the cases and of
      avoidable readmissions in 60%. The frequency of unforeseen readmissions was
      estimated at 3.9% of all conventional stays during the first half of 1997. The
      frequency of avoidable readmissions was 1.5%. CONCLUSIONS: Unforeseen early
      readmission can be an indicator of quality of the care taking process. It is
      however impossible to use the current database to classify with certainty
      readmissions as "unforeseeable" or "avoidable". Emergency unit readmission could
      offer a possible approach to measuring the frequency of unforeseen readmission.
      This ratio can provide caretakers with information concerning the quality of care
      and thus help in making decisions concerning reorganization for improvement.

PMID- 11319486
TI  - The causes of cancer.

PMID- 11319487
TI  - [Is there such a thing as brain fatigue?].

PMID- 11319488
TI  - [Orofacial idiopathic pain: clinical signs, causes and mechanisms].
AB  - Atypical facial pain, stomatodynia, atypical odontalgia, masticatory muscle and
      some temporomandibular joint disorders are grouped together under the category of
      orofacial idiopathic pain as they reveal numerous common clinical features. For
      each of these entities, problems of definition and terminology are discussed.
      Epidemiological and demographic data and a semiological description are given.
      Proposed diagnostic criteria and some of the causes or mechanisms common to these
      entities are also described in this article. Firstly, the role of female hormones
      in the physiology and treatment of certain patients is suggested with regard to
      the marked prevalence of changes in oestrogen levels in patients with orofacial
      idiopathic pain. Postmenopausal osteoporosis and the hypothesis of neuralgia due
      to the presence of cavities of osteonecrosis are placed within the context of
      atypical facial pain. A neuropathic component is suggested for these pain
      entities. These latter may be linked to a phenomenon of central sensitisation
      that is induced and maintained by activity in the peripheral tissues. Clinical
      features of both atypical facial pain and atypical odontalgia have led several
      authors to advocate the existence of a sympathetic mechanism in the
      physiopathology of these entities. Moreover, some arguments emphasize
      similarities with Complex Regional Pain Syndromes of limbs. Lastly, psychosocial
      components are also considered as a common factor, but it is currently impossible
      to determine if the pain is the cause or the result of psychosocial problems.
      Currently, none of these mechanisms can be considered as a single established
      etiological factor. Indeed, each of these mechanisms can be observed in all types
      of orofacial idiopathic pain. This leads to the hypothesis that these different
      mechanisms may act on each target tissue but the details of interaction are still
      unknown.

PMID- 11319489
TI  - [Toe phasic posture reflex: description and distribution among patients with
      neurological disease and in the general population].
AB  - A clinical sign is described consisting of a brief extension of the toes after
      upward tapping of the plantar surface of their terminal phalanges. Electrological
      data support the hypothesis of a long loop reflex, which we call the "toe phasic
      posture reflex" (TPPR). In a preliminary study, this sign was observed in
      patients with central nervous system disease, especially in subcortical brain
      disorders regardless of etiology. In Parkinson's disease, it was seen mostly in
      severe and postural forms. Among 237 healthy subjects, it was observed in none of
      those under 70 years old (n=116), and in 10p. cent of those over 69 years and
      doing no sport (n=132), but in none of those doing regularly gymnastics or
      swimming (n=29). TPPR could thus be a sign of motor and especially postural
      aging.

PMID- 11319490
TI  - [Musical hallucinosis following infarction of the right middle cerebral artery].
AB  - A 44-year-old woman demonstrated a musical hallucinosis four months after a
      massive infarction in the territory of the right middle cerebral artery. This
      musical hallucinosis consisting of familiar tunes, was continuous and perceived
      by both ears. Magnetic Resonance Imaging, middle and late auditory evoked
      potentials suggested that right Heschl's gyrus and associative areas were
      imparied. Audiometry demonstrated a low right transmission deafness. The
      hallucinosis was persistent for seven months and stopped just after hemorrhage of
      the right ear. This case gives the opportunity to review the different mechanisms
      responsible for musical hallucinosis.

PMID- 11319491
TI  - [Georges Gilles of Tourette, pioneer of gait analysis in the nervous system
      diseases].
AB  - Georges Gilles de la Tourette's contribution to neurology goes beyond the
      description of the neurological disorder named after him. On December 28, 1885,
      he defended his doctoral thesis devoted to "gait in the diseases of the nervous
      system, studied by the method of imprints". In collaboration with Albert Londe,
      he worked for two years in Charcot's department on "a simple method applicable to
      both healthy and unhealthy patients", establishing the scientific and modern
      basis of functional exploration of human gait. The purpose was to "record the
      modifications of the gait and to fix them permanently, using suitable devises to
      guarantee not only rigorous comparison, but also to prevent observers, making use
      of the same method, from disputing or canceling the results completely
      independent of the experimenter himself". Georges Gilles de la Tourette defined
      the various characteristic parameters and provided the normal reference values in
      males and females, determining the physiological asymmetry of steps. He described
      spastic gait, shaking palsy, and locomotor ataxia. He distinguished between
      disorders of nervous control and related joint diseases. He also classified gait
      disorders occurring during hemiplegia. Modern development of kinetic, kinematic
      and biomechanical studies is a good illustration of the current relevancy of
      Gilles de la Tourette's contribution.

PMID- 11319492
TI  - [Psychiatric disorders in juvenile myoclonic epilepsy].
AB  - Mild personality problems have been described in patients with juvenile myoclonic
      epilepsy (JME), but clinical practice shows that JME can be diagnosed in patients
      with more or less severe psychiatric disorders (PD). The presence in JME patients
      of personality disorders has been described repeatedly, but never quantified. We
      thus decided to evaluate, using the DSM IV, the current prevalence and types of
      PD in a large series of consecutive, newly referred patients with JME. Among 170
      consecutive JME cases referred to two departments of epileptology (Marseilles and
      Nice) between 1981 and 1998 (66 males, 104 females; aged 11.7-70; mean+/-SD
      32.4+/-10.4 follow-up 12.7+/-10 [0.5-52]), we found 45 patients (26.5p.100) with
      PD. According to the DSM IV, they could be classified as severe mental
      retardation (main diagnosis) (one case); pervasive developmental disorders (2
      cases); tic disorder (1 case); enuresis (1 case); psychotic disorders (5 cases,
      including schizophrenia paranoid type (1 case), disorganized type (1 case),
      delusional disorder (1 case), unspecified (2 cases)); depressive disorders (3
      cases); generalized anxiety (6 cases); anorexia nervosa (2 cases); personality
      disorders (24 cases, including borderline personality (11 cases), dependent
      personality (5 cases), histrionic personality (2 cases), obsessive-compulsive
      personality (1 case), not specified (5 cases)). Sudden unexplained death occurred
      in 2 cases (borderline personality and pervasive developmental disorder not
      otherwise specified, respectively) and death due to pneumonia in 1 cases
      (anorexia). Although uncommonly severe cases of JME may have been selected in our
      referral centers, it appears that JME may be associated with PD. Comparatively
      mild personality disorders are the most common finding, and may be part of the
      clinical picture to some extent, while severe PD are less common, and probably
      coincidental. The presence of PD does not exclude the diagnosis of JME, and PD
      may represent a further challenge in the comprehensive care of these patients.

PMID- 11319493
TI  - [Acute polyradiculoneuritis and dysautonomia: contribution of assaying
      catecholamines and their methoxylated metabolites].
AB  - Guillain-Barre syndrome is an acute demyelinating polyradiculoneuritis usually
      evolving with rapid, functional recovery. In severely paralysed patients, cranial
      nerve palsy and autonomic nervous system dysfunctions are common. Lesions of the
      spinal roots predominate but segmentary demyelination of peripheral nervous
      system reflects various clinical subtypes. Twelve patients (42,8 p. cent) had
      clinical dysautonomia. Ten had an increase of urinary methoxylated metabolites.
      Patients exempt of dysautonomia had normal biological parameters. The elevated
      level of urinary methoxylated metabolites is statistically correlated to clinical
      dysautonomia and can be used as a biological marker to monitoring demyelinating
      polyradiculoneuritis.

PMID- 11319494
TI  - [Trismus, pseudobulbar syndrome and cerebral deep venous thrombosis].
AB  - We report a case of cerebral deep venous thrombosis that manifested clinically by
      a pseudobulbar syndrome with major trismus, abnormal movements and static
      cerebellar syndrome. To our knowledge, only three other cases of deep cerebral
      venous thrombosis associated with cerebellar or pseudobulbar syndrome have been
      published since 1985. The relatively good prognosis in our patient could be
      explained by the partially intact internal cerebral veins as well as use of early
      anticoagulant therapy. There was a spontaneous hyperdensity of the falx cerebri
      and the tentorium cerebelli on the brain CT scan, an aspect highly contributive
      to diagnosis. This hyperdensity of the falx cerebri was found in 19 out of 22
      cases of deep venous thrombosis detailed in the literature.

PMID- 11319495
TI  - [Hemicontracture and facial myokimia as the first manifestation of multiple
      sclerosis].
AB  - Continuous facial myokimia (CFM) are characterized by a contracted facial
      appearance and vermicular movements that spread across a hemiface. Pontine
      lesions are their most frequent cause. Although their occurrence during the
      course of multiple sclerosis is not uncommun, CFM are rarely the first sign of
      the disease. We report two cases of CMF as first manifestation of multiple
      sclerosis. Multiple sclerosis is the first diagnosis to suspect in young people
      with CFM.

PMID- 11319496
TI  - [Effect of traumatic brain injury on control and suppression of inhibition
      processes].
AB  - Recent hypotheses have renewed discussion on the mechanisms linking executive
      functions and working memory in patients with traumatic brain injury. In this
      context, we studied the control and suppression functions of inhibition
      processes. Results obtained with a suppression paradigm showed that the traumatic
      brain injury patient makes a number of suppression errors and that suppression
      responses imply an important temporal loss in this population.

PMID- 11319497
TI  - [Benign acute ataxia in an adult with VZV infection].
AB  - In adults, neurological complications of VZV virus usually occur after herpes
      zoster infection in patients with AIDS. We report a case of acute and benign
      cerebellar ataxia after chickenpox in a patient without immunodeficiency.

PMID- 11319498
TI  - [Transient hemiballismus secondary to minimal head trauma].

PMID- 11319499
TI  - [Vascular dementia].

PMID- 11319500
TI  - [Kleine-Levin syndrome].

PMID- 11319501
TI  - [Fetal malformations diagnosed using ultrasonography during tri-test. A
      retrospective study of 1633 fetuses].
AB  - BACKGROUND: To find out which fetal malformations are diagnosed during the tri
      test. METHODS: A total of 1633 pregnant women were enrolled in the study and
      underwent biochemical screening for Down s syndrome and DTN at the Outpatient
      Clinic for Prenatal Diagnosis of  Santo Bambino  Hospital in Catania between
      January 1997 and December 1998. Scans were performed using a TA route in all
      cases and mainly during the 16th week. RESULTS: 21 abnormal fetuses were
      diagnosed, equal to 1 out of 77 fetuses (3 cases of isolated DTN; 1 case of cyst
      in the posterior cranial fossa associated with complex heart malformation; 6
      cases of cyst of the choroid plexus; 2 cases of bone dysplasia; 2 cases of
      cardiopathy; 4 cases of non-immunological fetal hydrops; 1 case of hygroma). In 8
      out of 21 abnormal fetuses the tri-test was positive for DNT and SD or atypical.
      One case of trisomy 18 and 1 case of mosaicism were diagnosed. CONCLUSIONS: A
      fetal abnormality was diagnosed in one out of 77 fetuses. This finding, although
      it underestimates the real frequency of these anomalies (retrospective study,
      selected sample, non optimal period for the diagnosis of fetal malformations, non
      systematic study of 4 chambers), once again underlines the importance of a
      careful morphological evaluation in eyery scan carried out. In our study some
      malformations were not diagnosed previously because this was the first scan (1
      case of anencephaly), or because the abnormality was presumably not present in
      earlier tests (bone dysplasia at early stage of pregnancy) or because the earlier
      test was inadequate (2 DTN tested after the 12th week). In some cases it is also
      possible to diagnose images, such as  transient  hygromas which indicate a group
      of patients with a risk of chromosome pathology. Since they are transient, these
      lesions are only found if the test is performed at a period of pregnancy before
      the optimal moment for the tri-test. In personal experience the execution of
      biochemical screening for Down s syndrome and DTN should always be associated
      with a scan not only to date the pregnancy, but also because it is not infrequent
      to diagnose malformations.

PMID- 11319502
TI  - [Laparoscopic treatment of ovarian cysts in women over 40].
AB  - BACKGROUND: Laparoscopy constitutes the main surgical method for treating benign
      ovarian pathology in women under 40 years of age. The discussion is about the
      possibility of extending this surgical method to patients over 40 in whom the
      risk of malignant ovarian pathology is either borderline or considerably higher.
      The objective of this study was to evaluate the feasibility of laparoscopic
      treatment for these patients, who have been submitted to adequate screening,
      comparing the results of echographic diagnosis, laparoscopy and histology.
      METHODS: This study includes 65 patients, all over 40 (average age 51 years,
      range 41-71 years): 34 were in menopause and 31 had a normal menstrual cycle. All
      were suffering from ovarian pathology. They were selected on the basis of a
      diagnostic protocol and then submitted to laparoscopic treatment and a follow-up
      check. RESULTS: The laparoscopic approach led to a clear improvement of the
      diagnosis compared to echography and dosage of the markers. The percentage of
      similarity between echographic and laparoscopic diagnosis was 84.6% while in the
      case of echographic diagnosis and histological examination this was 78%. The
      percentage of similarity between laparoscopic and histological diagnosis was 94%.
      Only one case of conversion to laparotomy occurred. CONCLUSIONS: Patients over 40
      years of age can present a wide range of pathologies that can be treated by means
      of laparoscopy. Never the-less, also when confronted with an unclear diagnosis,
      which would otherwise require laparotomy, the laparoscopic approach significantly
      improves of the diagnosis without any ultimate worsening of the prognosis.

PMID- 11319503
TI  - [Correlations between acne and polycystic ovary. A study of 60 cases].
AB  - BACKGROUND: In this paper we correlated the clinical severity of the polycystic
      ovary with the clinical manifestation of acne. Acne is an inflammatory process of
      follicle sebaceous unites. Polycystic ovaries (PCOS) are characterized by several
      subcapsular cystic follicles with an increased production of androgens. Onset of
      polycystic ovaries in women with acne, ranges from 45 to 84% of cases. METHODS:
      Sixty patients, aged from 19 to 28 years, with acne and polycystic ovaries were
      enrolled. The clinical severity of acne was appraised by millimetric
      macrophotography. This technique evaluated subsequent phases of acne like comedo,
      papules or pustules, nodular or scarring lesions. Polycystic ovaries were studied
      by ultrasound and hormonal assay. Sonora Logic 500 MD, by GE Echography, with 3.5
      MHz convex probe, were employed. US examination was performed, in each patient,
      on day 6th, 10th, 15th and 22th of the menstrual cycle. The following US
      parameters were considered: dimension of the ovaries, thickness of albuginea and
      number of cysts. Serum levels of FSH, LH, 17-b-estradiol, progesterone, DHEA-S,
      testosterone and LH/FSH ratio were determined. Furthermore, the presence of
      premenstrual syndrome (PMS) was evaluated. RESULTS: We found that in PCOS the
      increased levels of androgens can cause the onset of acne. Photographic score and
      ovaries ultrasonography may be useful in the assessment of the clinical
      association between acne and polycystic ovaries. We observed that the subsequent
      phases of acne were correlated with the clinical severity of polycystic ovaries
      and to the presence of Premenstrual Syndrome in 93% of the cases (56 of 60
      patients). CONCLUSIONS: US images, compared with visual score, established the
      clinical association between acne and PCOS in three phases with a progressive
      severity.

PMID- 11319504
TI  - [Embryo-fetal diseases in multiple pregnancies].
AB  - BACKGROUND: Embryo-fetal diseases are the consequence of prenatal (progenetic and
      metagenetic or environmental) and intranatal (of a traumatic, infective, toxic
      nature) pathological factors. In multiple pregnancies this complex
      etiopathogenesis also includes an altered didymous embriogenesis. This study
      aimed to evaluate the pathologies affecting the fetus in multiple pregnancy, a
      special biological situation leading to the potential onset of severe fetal and
      neonatal damage. METHODS: The authors studied 205 patients with multiple
      pregnancies, including 199 bigeminal, 5 trigeminal and 1 quadrigeminal, admitted
      to the Department  B  of the Obstetrics and Gynecological Clinic of Turin
      University between 1989-1999. Possible embyro-fetal damage was examined using a
      chronological criterion: namely following the development of the multiple fetuses
      from the zygotic to the neonatal phase. RESULTS: Pregnancies were biamniotic
      bichorionic in 54% of cases, biamniotic monochorionic in 45% and monochorionic
      monoamniotic in 1%. There were a total of 154 (79.38%) premature births out of
      194 and neonatal birth weight was always SGA (small for gestational age). 66.84%
      of newborns were LBW (<2500 g) and 7.14% were VLBW (<1500 g). Fetal mortality
      (2.29%) was higher than early neonatal mortality (1.53%). Perinatal mortality
      (3.82%) was three times higher than in all neonates from the same period (1.03%).
      CONCLUSIONS: The severe embryo-fetal and neonatal damage found in multiple
      pregnancies is a clinical reality that calls for adequate diagnostic and
      therapeutic measures, and above all specific medical and social prevention to
      limit maternal pathogenic risks.

PMID- 11319505
TI  - [Current epidemiologic features of septic abortion].
AB  - BACKGROUND: This article deals with the current epidemiological features of
      septic abortion. METHODS: Forty-two of 431 abortions (9,74%) were diagnosed as
      septic abortions during 1998 at the I and II Institute of Obstetrics and
      Gynecology, University of Rome La Sapienza , and are retrospectively analyzed.
      RESULTS: Thirty-four women (81%) came from an EEC country, whereas 8 (19%) from a
      developing country. Their mean age was 31,4 years (range: 18-43 years). Eighteen
      patients (43%) were nulliparous; 24 (57%) multiparous; 14 (33%) had previous
      abortions, none had previous septic abortions. Among risk factors, premature
      rupture of membranes was found in 5 cases (12%); whereas amniocentesis, HIV
      positivity, diabetes, positive urine culture and illegal pregnancy termination
      procedures were found in 5 further cases. No risk factors were found in 76% of
      patients. CONCLUSIONS: It is observed that, due to medical-scientific advances,
      previously unknown risk factors have emerged during the last three decades in
      Western Countries, such as invasive procedures of prenatal diagnosis, IUD
      contraception and AIDS immunodepression. However, other previously frequent risk
      factors, such as sepsis from illegal abortion, may emerge again in Countries
      where abortion is legal (such as Italy), due to massive immigration of
      clandestine women from developing Countries.

PMID- 11319506
TI  - [An alternative to postmenopausal Hormone Replacement Therapy? Selective
      Estrogens Receptors Modulators (SERMs)].
AB  - Hormone Replacement Therapy (HRT) represents the first and probably sole
      therapeutically approach for prevention and treatment of medical postmenopausal
      disease. Nevertheless, the adverse effects and the risks HRT associated,
      suggested, to clinical and pharmaceutical research new pharmacological treatment
      options. Actually a group of compounds, SERMs (Selective Estrogen Receptor
      Modulators), allows a large interest. These pharmacological agents, due to their
      estrogen agonist/antagonist properties, are able to bind Estrogen Receptors in
      female target tissues (bone, brain, heart, etc) with different actions; so, by
      these properties, SERMs represent actually a possible alternative to HRT.

PMID- 11319507
TI  - [Vesicouterine fistula and bladder endometriosis. A case report].
AB  - Vesicouterine fistula is rare, accounting nearly 4% of all urogenital fistulas.
      Cesarean delivery through uterine lower segment is the main predisposing event
      but in the last years other possible predisposing factors have been pointed out.
      Clinically, it can occur in different forms and the diagnosis is often delayed
      although it is not difficult. In this study personal experience in a case of
      postcesarean vesicouterine fistula arisen on a focus of bladder endometriosis is
      reported and an eventual hypothetical pathogenetic correlation between bladder
      endometriosis and vesicouterine fistula is discussed.

PMID- 11319508
TI  - [Effect of estriol treatment per vaginam before Burch culposuspension].
AB  - BACKGROUND: To assess the effect of estriol treatment per vaginam before Burch
      culposuspension in postmenopausal women with stress urinary incontinence (IUS).
      METHODS:  DESIGN: prospective randomised study. SETTING: Department of
      Gynaecology, Obstetrics and Physiopathology of Human Reproduction-Medical School
      University of Naples  Federico II . PATIENTS: twenty women in postmenopause at
      least from five years with a urogenital symptomatology due to IUS. INTERVENTIONS:
      women were randomised into one of two groups (treated or control) and they were
      submitted to an evaluation of vulva and vagina trophism. All the women were
      submitted to a urodynamic examination and to a transvaginal ultrasonography with
      evaluation of pubis-bladder neck distance, bladder and proximal urethra position,
      before treatment, one week before the operation and after six months from the
      same operation. EVALUATIONS: subjective symptomatology and urodynamic parameters
      between treated and control groups before and after operation. RESULTS: After 12
      weeks of treatment, a significant improvement of subjective symptomatology and a
      not significant improvement of all the urodynamic parameters in the treated group
      in comparison with the control group have been demonstrated, while any anatomic
      alteration compared with the basal hasn t been observed. After six months from
      the operation in all the women a significant reduction of subjective quantity of
      urine lost after a strain has been demonstrated and significant variations of
      urodynamic parameters without significant differences between treated group and
      control group were also observed. CONCLUSIONS: The estriol treatment per vaginam
      is not so effective on the result of Burch culposuspension in postmenopausal
      women with IUS.

PMID- 11319509
TI  - [Ethical problems concerning artificial fecondation].
AB  - In view of the seriousness of the facts regarding artificial fecondation as
      reported in the news and by the mass media, the various experiments carried out
      are analysed from the anthropological and ethical points of view. The purpose of
      these experiments is the procreation of a person and all those who are implicated
      in  vital  decisions-physicians, nurses, legislators and families-are invited to
      refrain from carrying out experiments or actions that might be damaging to the
      dignity of people and the couple in question.

PMID- 11319510
TI  - Th2 cytokine role in autoimmune haemolytic anaemia (AIHA) pathogenesis.
AB  - BACKGROUND: AIHA is characterised by the destruction of antibody-coated red blood
      cells, but the mechanism that initiates the production of autoantibodies remains
      unclear. We have studied the proliferative response and the spontaneous and
      mitogen-induced (PHA and OKT3) synthesis of IFN-g, IL-2 and IL-4 by peripheral
      blood mononuclear cells from patients with AIHA before any treatment to
      investigate the activation of Th1 and Th2 subsets. METHODS: Thirteen AIHA
      patients, both idiopathic and associated with other diseases, were studied by
      ELISA methods and H3 thymidine incorporation to determine in vitro cytokine
      production and T cell proliferative response, respectively. RESULTS: Under basal
      conditions the proliferative response induced in peripheral blood mononuclear
      cells was enhanced in AIHA patients suggesting a basal state of hyperactivation.
      This increase in proliferative response can be related to the basal enhanced
      levels of IL-2 (p<0.04), a key cytokine, that regulates the growth,
      differentiation and function of lymphocytes. High IL-2 levels in AIHA patients
      supernatants, with or without OKT3 stimulation, justify the high basal activation
      of T lymphocytes. Under basal conditions levels of IFN-g are decreased and IL-4
      levels are increased. CONCLUSIONS: AIHA is characterised by the destruction of
      antibody-coated red blood cells, but the mechanism that initiates the production
      of autoantibodies remains unclear. But looking to this data it is possible to
      suppose that there is a prevalent contribution of Th2 lymphocytes to the
      pathogenesis of AIHA.

PMID- 11319511
TI  - Chronobiology of non fatal pulmonary thromboembolism.
AB  - BACKGROUND: It as been demonstrated that acute myocardial infarction, sudden
      cardiac death, stroke, and fatal pulmonary embolism show an increased onset rate
      during certain periods of the day, week, or year. According to some authors, the
      highest risk appears to occur in the morning, on weekends and during winter. This
      paper, therefore, intends to examine whether a circadian, weekly, or annual
      rhythm in the incidence rate of deep vein thrombosis (DVT) and non-fatal
      pulmonary embolism (PE) in ageing patients does exists. METHODS: A survey was
      conducted into 212 patients affected by DVT and PE, admitted to the Second
      Medicine Institute of Padua, Italy, over a period of two solar years. Thromboses
      were diagnosed via echo-Doppler examination of the legs and pulmonary embolism
      via perfusive and ventilatory scintiphotographs. RESULTS: In the overall sample,
      a circadian variation was found, both for deep vein thrombosis (peak at 12:26
      hrs, p=0.001), and pulmonary embolism (peak at 10:26 hrs, p=0.001). A weekly,
      rhythmic recurrence was also found for the two complaints, with a peak on
      Saturdays, while no significant annual rhythmic recurrence was found. There was,
      however, a tendency towards an increase during the winter and summer months.
      CONCLUSIONS: The results may have important clinical applications, both in
      prevention and in the  timing  of drug dosage.

PMID- 11319512
TI  - The influence of somatostatin on bacterial translocation.
AB  - BACKGROUND: Bacterial translocation is defined as the passage of bacteria from
      the gastrointestinal tract to extraintestinal sites mostly as a consequence of
      the loss of the gut barrier function. Somatostatin and octreotide, exerting many
      inhibitory effects on the gastrointestinal tract, have been evidenced to promote
      bacterial translocation. METHODS:  DESIGN: experimental research. SETTING:
      University teaching Hospital. INTERVENTIONS: Sixteen pigs forming the study group
      received 25 mg/kg of octreotide twice a day for ten days. A control group (n=16)
      received an equal volume of saline solution for the same period. All animals were
      sacrificed and tissue cultures were obtained from mesenteric lymph nodes (MLN),
      liver and spleen. Portal venous and central venous blood samples were also
      withdrawn for culture. RESULTS: In the octreotide group, cultures were positive
      for bacteria in 43.7% (7/16) of animals. Viable bacteria were recovered from MLN,
      liver and spleen. Portal and systemic blood cultures showed no growth of
      bacteria. The mean value of bacterial detection in MLN, liver and spleen was
      196+/-13 CFU/g, 190+/-26 CFU/g, and 173+/-0 CFU/g, respectively. P value was not
      statistically significant. Bacterial translocation did not occur in the animals
      of the control group. Fisher s exact test revealed a statistically significant
      difference (p<0.007) between the two groups regarding bacterial translocation to
      MLN. CONCLUSIONS: The administration of octreotide is followed by a conspicuous
      increase in bacterial translocation in pigs. Further clinical studies are needed
      to demonstrate similar effects on humans.

PMID- 11319514
TI  - Endoscopy and surgery. A combined strategy for diagnosis and therapy of polyposis
      cancer sequence in the colon.
AB  - BACKGROUND: The aim of the paper is to evaluate retrospectively the series of
      patients affected by colon polyps and colon cancer to purpose a planned follow-up
      for patients who underwent colon polypectomy. METHODS: Out of 198 patients
      affected by colon carcinoma, the authors describe 95 cases of previous,
      synchronous or metachronous polyps, with a global prevalence of 47.9%, and
      respectively of 13.6%, 16.6%, and 17.6%. RESULTS: The evolutive sequence between
      colon polyp and carcinoma is shown through both clinical experience and
      experimental tests. The epidemiologic curve of adenoma rate precedes by five
      years the curve of carcinoma, and such is the average period of time for the
      transformation of an adenoma into invasive carcinoma. In clinical practice, it is
      frequent to note synchronous or metachronous polyps with respect to colon
      carcinoma. It is also possible to note carcinoma in patients with previous
      polypectomies. CONCLUSIONS: On the basis of the retrospective evaluation of the
      clinical cases, and reviewing international literature, the authors suggest their
      diagnostic-therapeutic and endoscopic follow-up protocol for patients affected by
      colon neoformations (Fig. 1).

PMID- 11319513
TI  - Gemcitabine as single agent therapy in advanced non small cell lung cancer and
      quality of life in the elderly.
AB  - BACKGROUND: The aim of this study is to test the efficacy of gemcitabine as
      single agent therapy in advanced non-small cell lung cancer in the elderly by the
      evaluation of the clinical response, the survival increase and the quality of
      life. METHODS: Nineteen patients (age >65 years) with a PS >2, bearing an
      advanced non-small cell lung cancer (IIIb-IV) not treated with chemotherapy
      before, were charged between December 1996 and December 1998. Sixteen patients
      were treated with gemcitabine at the dose of 1000 mg/mq 1-8-15 every 28 days. CT
      scan, X-rays and skeletal scintigraphy were used in the evaluation of the
      therapeutic response. The toxicity was estimated by following WHO indexes. The
      quality of life and the modification of the specific symptoms were estimated by
      particular tests (Spitzer Index, IADL, EORTC-LC13). RESULTS: One complete
      response (6%), 4 partial responses (25%), 7 cases of illness stabilization (43%),
      4 cases of illness progression, were shown. One year of survival was found in 43%
      of cases with a 14 week of therapeutic response and a global survival ratio of
      12.4 weeks. Only 2 cases (12.5) of medium grade G3-leucopenia were found. All
      patients improved their quality of life (IADL and Spitzer indexes) with reduction
      of symptoms, (EORTC-LC13) and increase of self-agin and relationships.
      CONCLUSIONS: The effectiveness of gemcitabine as single agent therapy as not yet
      been tested due to the scanty number of patients, nevertheless it must be
      considered in relation to the improvement of the patient s quality of life.

PMID- 11319515
TI  - Oxidative stress status: possible guideline for clinical management of critically
      ill patients.
AB  - BACKGROUND: Critical care medicine has developed in the last few years into a
      separate scientific discipline and studies related to the outcome after intensive
      care usually suggest a long hospital stay that becomes cost prohibitive. The
      majority of problems (death) amongst critically ill patients requiring critical
      care involve sepsis, inflammation, tissue damage-oxidative stress, oxygen tension
      PO2, lipid peroxidation. The present investigation involves monitoring of serum
      levels of MDA, SOD as a possible guideline for severity of clinical situations in
      critically ill patients. METHODS: Fifty critically ill heterogeneous patients
      requiring intensive care in the ICU of IKDRC were selected as subjects with ages
      varying from 17 to 75 years. Serum levels of MDA (ng/ml), SOD (U/ml) were
      determined right from admission to discharge due to improvement / DAMA / death.
      MDA and SOD were estimated according to the methods of Buege and Aust et al.
      (1978), Nandi and Chatterji (1988). RESULTS: Critically ill patients irrespective
      of the disease process indicated significantly very high serum levels of MDA and
      low levels of SOD at the time of admission (13.28+/-4.26 ng/ml, 3.80+/-2.60 U/ml,
      respectively) according to the severity of the prevalent clinical situation. The
      pattern of serum levels of MDA and SOD according to subsequent clinical
      performance did indicate a decreasing trend of MDA (oxidant) and fluctuating
      trend of SOD (antioxidant enzyme except in those who inevitably succumbed to
      death in spite of adequate clinical management. CONCLUSIONS: The results of the
      present study have amply revealed the utility and relevance of monitoring
      oxidative stress in critically ill patients as biochemical markers, cost
      effectiveness and role in decision making (withdrawal/continuation of different
      support modalities) as deemed fit.

PMID- 11319516
TI  - The development of the suprarenal gland: surgical and anatomical considerations.
AB  - BACKGROUND: Aim of this research is to study the situation and relationships of
      the adrenal gland in the first stage of development in order to give some
      contributes for the application of laparoscopic adrenalectomy; in the meantime we
      describe the series of the debate changes occurring in the constitution of the
      cortex and medulla. METHODS: Analysis of histologic slices of thoraco-abdominal
      and abdominal regions of human embryos and fetuses ranging from the fifth (12 mm
      CR) to the twentieth week (170 mm CR). RESULTS: At 12 mm CR an unique type of
      cells is present in the cortex; at 16 mm CR there are two different groups of
      cells. Sympathogonia enter into the cortex at 16 mm CR. The right adrenal gland
      seems enclosed into the liver and a ligament containing the middle adrenal vein
      reaches the vena cava inferior sulcus. The left adrenal gland, through the
      coelomic cavity, is in relationship with the stomach, the medial border of the
      spleen and the pancreatic body contained in the primitive dorsal mesogastrium.
      CONCLUSIONS: The timing of penetration of the ganglion cells into the cortex is
      defined as well as the hypothesis that the matrix of the fetal and definitive
      cortex is the same: moreover the study of the early development allows to
      understand the main characteristics of both the adrenal glands which are
      significant for a rational and differential laparoscopic approach.

PMID- 11319517
TI  - Perfusion of the subarachnoid space in cadavers: a technique applicable for
      prevention of paraplegia in surgery of the thoracic aorta.
AB  - BACKGROUND: No safe technique of subarachnoid perfusion during thoracoabdominal
      aneurysm surgery has been described. We tested the hypothesis that in cold
      cadavers, perfusion of the subarachnoid space at the lumbar level with warm
      solution is feasible and increases the temperature at the thoracic level without
      an increase in cerebrospinal fluid (CSF) pressure. METHODS: Six cadavers were
      used. A 5 Fr silastic catheter in the subarachnoid space between the second and
      third lumbar vertebra (L2-3) was used as an inflow and a 16-gauge catheter at L4
      5 as an outflow. Normal saline at 38 degrees C was infused at 999 mL/h.
      Temperatures of inflow and outflow, of the thoracic subarachnoid space (T8), and
      of the cisterna magna, were recorded. CSF pressures were measured from the
      outflow catheter. RESULTS: Outflow temperature was 9+/-1 degrees C at 10 minutes.
      At 15 minutes it was 27+/-4 degrees C, and thoracic subarachnoid temperatures was
      22+/-5 degrees C. There was no statistical difference between the temperatures
      recorded at 10 and 15 minutes. The temperature of the cisterna magna was 8.5+/
      1.2 degrees C at 15 minutes, significantly higher than the baseline (p=0.01), but
      lower than that at the T8 level (p=0.0001). CSF pressures during the experiment
      did not changed significantly from baseline and remained below 10 cm H20.
      CONCLUSIONS: The technique described is simple to implement, and effective in
      changing the temperature of the subarachnoid space at the thoracic level. Whether
      spinal cord cooling by this technique safely reduces the risk of paraplegia
      remains to be established in an animal model.

PMID- 11319518
TI  - Endothelin and diabetic nephropathy: a new pathogenetic factor?
AB  - Endothelin is a vasoconstrictor and a mitogenic peptide. It is able in vivo as
      well as in vitro to affect renal function and structure. Experiments conducted on
      animal models have shown that diabetes mellitus is associated with an increase in
      urinary and plasma endothelin levels. This increase, is probably correlated to
      renal damage progression and to characteristic alterations in diabetic
      nephropathy. Also studies conducted on diabetic patients have demonstrated an
      increase in plasma endothelin. The role of endothelin should therefore be
      considered because it could be involved in the pathogenesis of diabetic
      nephropathy.

PMID- 11319519
TI  - Focal segmental glomerulosclerosis and hepatitis C virus: a case report.
AB  - Focal segmental glomerulosclerosis (FSGS) is a renal disease characterized by
      sclerotic segmentary lesions, involving a few glomeruli. Male-female ratio is >1
      and, in the majority of cases, the patients are aged between 25 to 35 years. The
      clinical picture is similar to a nephrotic syndrome with non-selective
      proteinuria poorly sensitive to steroids and often associated with
      microhematuria. The etiology is still unknown, even in a prevalence in drug
      addicts, patients with AIDS and subjects with recurrent urological infections
      with vesico-ureteral reflux was observed. Recent reports showed that chronic
      infection Hepatitis C Virus (HCV)-related may be associate with or responsible
      for onset of some syndrome involving the kidney but not the liver. We report the
      case of a young woman with HCV-Ab positive chronic hepatitis that, during the
      disease, showed clinical findings of renal involvement, histologically related to
      a FSGS. We administered to her alpha-IFN at doses of 3 Mega Units thrice-a-week
      for six months. Serum HCV-RNA, proteinuria and hematuria disappeared
      simultaneously after the treatment. We underline that the lack of finding of HCV
      antigens or HCV-RNA in glomerular lesions (as occurred in our patient) does not
      rule out the virus role in pathogenesis of immunological nephritis. The recovery
      of our patient as well as the disappearance of proteinuria and hematuria during
      IFNalpha treatment may be further evidence that FSGS and chronic hepatitis HCV
      related are not associated by chance. Further observations and perfectioning of
      diagnostic techniques are required to clarify the pathogenetic relationship
      between HCV and renal immunological syndromes.

PMID- 11319520
TI  - Collagenous colitis in symptomatic subjects without endoscopic morphologic
      evidence: case report.
AB  - Collagenous colitis (CC) is a rare pathology and, even though various
      etiopathogenetic hypotheses have been put forward, the etiology and pathology are
      still not well defined. We report the case of a female patient suffering from
      chronic watery diarrhoea, positive for guaiac-based fecal occult blood test and
      morphologically negative to endoscopic investigation, but histologically
      classifiable as CC. This case report suggests that the clinical history must lead
      towards the execution of a colonoscopy with bioptic samples done even on
      apparently normal mucosa. Furthermore, the clinic should always signal a suspect
      CC to the anatomopathologist in order to have a correct diagnosis.

PMID- 11319521
TI  - Quality evaluation of health care offered by an Internal Medicine Department.
AB  - BACKGROUND: The aim of this work is to evaluate the quality and patients 
      satisfaction for given services in an Internal Medicine Department during three
      months. METHODS: A questionnaire was given to all the patients admitted to our
      Medicine Department to evaluate our strength and to correct weakness. RESULTS:
      Our patients assessed doctors and nursing staff for skill and dedication. They
      gave suggestions about hotel management: bathroom cleaning and number of beds in
      the same room. They also asked for a pharmacy and a post office inside the
      hospital. CONCLUSIONS: It appears that our ward gives a satisfactory health care
      situation. Some of our patients  suggestions can be put into practice in a short
      time, while others require longer, depending on public resources and not on
      private, such as happens, on the contrary, in the United States.

PMID- 11319526
TI  - Load distribution in extension saddle partial dentures. 1952.

PMID- 11319527
TI  - Restorative and orthodontic treatment of maxillary peg incisors: a clinical
      report.
AB  - This clinical report describes a combination treatment approach to an esthetic
      defect that resulted from diastemata and peg-shaped lateral incisors. Minor tooth
      movement was achieved through the use of a removable orthodontic appliance and
      orthodontic rubber band, and full-coverage PFM crowns were placed on the lateral
      incisors. These complementary orthodontic and restorative procedures successfully
      corrected the defect.

PMID- 11319528
TI  - Prosthetic considerations in the restoration of orthodontically treated maxillary
      lateral incisors to replace missing central incisors: a clinical report.
AB  - The treatment of young patients with missing maxillary incisors poses a challenge
      to prosthodontists and orthodontists. The 2 principal treatment options are (1)
      the reopening or maintenance of space for future autotransplantation and/or
      prosthodontic restoration of the missing teeth, or (2) total orthodontic space
      closure, followed by prosthodontic modification of the lateral incisors to
      simulate the central incisors. This article discusses only the second option and
      describes 2 alternative methods for the modification of crown anatomy. These
      procedures facilitate the orthodontic closure of missing central incisor spaces
      to ensure satisfactory, esthetic results.

PMID- 11319529
TI  - Bimaxillary soft splints for unconscious hard-clenching patients: a clinical
      report.

PMID- 11319530
TI  - Cement-retained prostheses in implant dentistry: a clinical report.

PMID- 11319531
TI  - Augmentation of obturator retention by extension into the nasal aperture: a
      clinical report.

PMID- 11319532
TI  - Effects of triclosan on the cytotoxicity and fungal growth on a soft denture
      liner.
AB  - STATEMENT OF PROBLEM: Contamination of removable prostheses with microorganisms,
      particularly Candida albicans, is a common clinical problem. Microban, a broad
      spectrum antimicrobial containing triclosan, recently has been proposed to
      inhibit microbial growth. PURPOSE: This study aimed to determine whether the
      addition of Microban to PermaSoft denture liner prevents the growth of C albicans
      and affects the cytotoxicity of the PermaSoft material. MATERIAL AND METHODS:
      Experimental specimen disks (5 x 1 mm each) with and without incorporated
      Microban were fabricated aseptically (n = 6) against polyester film to produce a
      smooth surface. To assess the cytotoxic effect of Microban, the MTT assay was
      used. To determine the effect of Microban on the growth of C albicans, disks were
      placed in Transwell dishes, covered with Sabouraud's broth containing an ATCC
      strain of C albicans, and incubated at 37 degrees C for 24 hours. Wells
      containing fluorocarbon resin disks or broth alone served as controls. The disks
      were rinsed to remove unattached C albicans and then sonicated in sterile water
      to remove surface organisms. Serial dilutions of the water extracts were plated
      on Sabouraud's agar and returned to the incubator for 24 hours. Colonies were
      counted with a Brunswick Colony Counter. Growth of C albicans in the internal
      aspects of the specimens was determined in a manner as previously described, with
      the exception that the specimens were sonicated to remove surface organisms,
      minced, and sonicated once more before making serial dilutions. The results were
      compared with ANOVA and Tukey intervals (alpha=.05). RESULTS: The number of
      colonies formed ranged from 17 to 31 x 10(5) (mean = 23 +/- 4 x 10(5)) and 14 to
      69 x 10(5) (mean = 32 +/- 20 x 10(5)) for the PermaSoft with and without Microban
      groups, respectively. There was no statistically significant difference between
      PermaSoft with and without Microban. CONCLUSION: The addition of Microban did not
      significantly alter the cytotoxicity of the PermaSoft denture lining material or
      reduce the adherence of viable C albicans to the surface of PermaSoft material
      after 24 hours.

PMID- 11319533
TI  - New method for divesting cobalt-chromium alloy castings: sandblasting with a
      mixed abrasive powder.
AB  - STATEMENT OF PROBLEM: Because the conventional divesting method for cobalt
      chromium (Co-Cr) alloys is laborious, a more convenient method is desirable.
      PURPOSE: This study compared sandblasting with a mixed powder composed of
      aluminum oxide and glass beads to sandblasting with single powders (carborundum,
      aluminum oxide, and glass beads) when a Co-Cr casting was removed from the
      investment mold. MATERIAL AND METHODS: Rectangular plates with the 2 surfaces
      simulating the inner and outer surfaces of a removable partial denture framework
      were fabricated with Co-Cr alloys. Four kinds of sandblasting powders were used
      to remove the remnants of investment molds. Total time (seconds) required for
      each procedure was measured, as was the surface roughness (Ra) of each specimen
      after sandblasting. SEM was used to analyze the powders themselves and the
      sandblasted specimen surfaces. RESULTS: Glass beads alone and the mixed powder of
      aluminum oxide and glass beads generated a smoother surface compared with
      aluminum oxide and carborundum powders. The use of the mixed powder significantly
      reduced the time of the sandblasting procedure. SEM revealed that glass beads
      generated fewer scars, followed by the mixed powder and then aluminum oxide. The
      surface sandblasted by carborundum powder was always the roughest. CONCLUSION:
      Sandblasting Co-Cr castings with the mixed powder effectively decreased treatment
      time and resulted in smooth, clinically acceptable casting surfaces.

PMID- 11319534
TI  - Tooth preparations for complete crowns: an art form based on scientific
      principles.
AB  - STATEMENT OF THE PROBLEM: No recent literature has reviewed the current
      scientific knowledge on complete coverage tooth preparations. PURPOSE: This
      article traces the historic evolution of complete coverage tooth preparations and
      identifies guidelines for scientific tooth preparations. MATERIAL AND METHODS:
      Literature covering 250 years of clinical practice was reviewed with emphasis on
      scientific data acquired during the last 50 years. Both a MEDLINE search and an
      extensive manual search were used to locate relevant articles written in English
      in the last 50 years. RESULTS: Teeth should be prepared so that they exhibit the
      following characteristics: 10 to 20 degrees of total occlusal convergence, a
      minimal occlusocervical dimension of 4 mm for molars and 3 mm for other teeth,
      and an occlusocervical-to-faciolingual dimension ratio of 0.4 or greater.
      Facioproximal and linguoproximal line angles should be preserved whenever
      possible. When the above features are missing, the teeth should be modified with
      auxiliary resistance features such as axial grooves or boxes, preferably on
      proximal surfaces. Finish line selection should be based on the type of
      crown/retainer, esthetic requirements, ease of formation, and personal
      experience. Expectations of enhanced marginal fit with certain finish lines could
      not be validated by recent research. Esthetic requirements and tooth conditions
      determine finish line locations relative to the gingiva, with a supragingival
      location being more acceptable. Line angles should be rounded, and a reasonable
      degree of surface smoothness is desired. CONCLUSIONS: Nine scientific principles
      have been developed that ensure mechanical, biologic, and esthetic success for
      tooth preparation of complete coverage restorations.

PMID- 11319535
TI  - Implant-induced expansion of atrophic ridges for the placement of implants.
AB  - The applicability of endosseous implants is directly related to the topography
      and quality of the patient's residual bone. Several techniques have tried to
      expand the applicability through implant design alterations and surgical
      techniques for bone augmentation. This article describes an implant-induced bone
      expansion procedure that facilitates the placement of implants in atrophic
      alveolar ridges. This procedure expands the cortical plates of the alveolar
      ridges with or without fracture using wedge-shaped implants and the principles of
      guided tissue regeneration. The use of implants of larger diameters and the
      remodeling of the ridge external contour can be achieved with this procedure.

PMID- 11319536
TI  - Immediate loading of single root form implants with the use of a custom acrylic
      stent.
AB  - This article describes a technique for fabricating a provisional screw-retained
      restoration for immediate loading of single implants. Until immediate loading of
      single implants becomes a well-documented treatment modality, this technique
      should be used cautiously.

PMID- 11319537
TI  - A comparison of the wear resistance and hardness of indirect composite resins.
AB  - STATEMENT OF PROBLEM: Various new, second-generation indirect composites have
      been developed with claimed advantages over existing tooth-colored restorative
      materials. To date, little independent research has been published on these
      materials, and the properties specified in the advertising materials are largely
      derived from in-house or contracted testing. PURPOSE: Four second-generation
      indirect composites (Artglass, belleGlass, Sculpture, and Targis) were tested for
      wear resistance and hardness against 2 control materials with well-documented
      clinical application. Human enamel was also tested for comparison. MATERIAL AND
      METHODS: Twelve specimens of each material were fabricated according to the
      manufacturers' directions and subjected to accelerated wear in a 3-body abrasion,
      toothbrushing apparatus. Vickers hardness was measured for each of the tested
      materials, and energy dispersive x-ray (EDX) spectroscopy was performed to
      determine the elemental composition of the composite fillers. The statistical
      tests used for wear and hardness were the Kruskal-Wallis 1-way ANOVA test with
      Mann-Whitney tests and 1-way ANOVA with multiple comparisons (Tukey HSD). The
      Pearson correlation coefficient was used to determine the existence of a
      relationship between the hardness of the materials and the degree to which they
      had worn. The level of statistical significance chosen was alpha=.05. RESULTS:
      The control material Concept was superior to the other composites in wear
      resistance and hardness and had the lowest surface roughness. Significant
      relationships were observed between depth of wear and hardness and between depth
      of wear and average surface roughness. Enamel specimens were harder and more wear
      resistant than any of the composites. EDX spectroscopy revealed that the
      elemental composition of the fillers of the 4 new composites was almost
      identical, as was the composition of the 2 control composites. CONCLUSION: The
      differences in wear, hardness, and average surface roughness may have been due to
      differences in the chemistry or method of polymerization of the composites.
      Further research in this area should be encouraged. It was also apparent that the
      filler present in the tested composites did not exactly fit the manufacturers'
      descriptions.

PMID- 11319538
TI  - Shear peel bond strength of compomers veneered to amalgam.
AB  - STATEMENT OF PROBLEM: The practice of veneering compomers to amalgam restorations
      has not been studied. PURPOSE: This in vitro study was designed to assess the
      shear peel bond strength and fracture pattern of 3 currently available compomers
      veneered to amalgam. MATERIAL AND METHODS: Sixty cylindrical preparations were
      filled with amalgam. Half (30) had no surface treatment, whereas the other half
      were air abraded. In both groups, 10 specimens each were veneered with Dyract AP,
      Hytac, and F2000 according to the manufacturers' instructions. All samples were
      kept at 37 degrees C in 100% relative humidity for 48 hours. SPBS was assessed
      with a universal testing machine and fracture patterns with a stereomicroscope.
      The results were analyzed with 2-way ANOVA and Tukey's multiple comparison test.
      RESULTS: Dyract AP veneered to air-abraded amalgam had the highest SPBS (5.78 +/-
      1.30 MPa); F2000 veneered to non-air-abraded amalgam had the lowest (2.99 +/- 1.4
      MPa). Sandblasting significantly influenced SPBS in the case of Hytac (P<.02) and
      F2000 (P<.01). Within the non-air-abraded group, Dyract AP had significantly
      higher SPBS than Hytac (P<.03) and F2000 (P<.015). F2000 air-abraded specimens
      exhibited adhesive bond failure only, whereas all other groups showed both
      adhesive and combined bond failures. CONCLUSION: Of the 3 compomers tested for
      veneering to amalgam, Dyract AP showed the highest SPBS. Air-abrading the amalgam
      surface was found to improve the SPBS of Dyract AP, though not significantly. Low
      SPBS and poor adhesion indicated that F2000 is unsuitable for veneering amalgam.

PMID- 11319539
TI  - In vitro testing of the bond between soft materials used for maxillofacial
      prostheses and cast titanium.
AB  - STATEMENT OF PROBLEM: The choice of soft materials for maxillofacial prostheses
      is important for covering extraoral defects after tumor surgery or radiation
      therapy. The use of cast commercially pure titanium as reinforcement seems to be
      a suitable option. PURPOSE: Making use of the advantages of titanium frameworks
      for maxillofacial prostheses requires exploring ways of combining it with soft
      materials. This study investigated such combinations and evaluated discoloration
      of the soft material to determine whether it was attributable to the titanium
      reinforcement. MATERIAL AND METHODS: Five soft materials used for maxillofacial
      prostheses and their bond strengths to cast titanium were tested. Different ways
      of conditioning the titanium surface and different adhesives were used. Plain
      mechanical retention was also studied. The Gretag SPM 100 was used to determine
      the potential effects on coloring after 24 hours of radiation in the Suntest
      rapid exposure unit. RESULTS: Suitable material combinations for bonding soft
      materials to titanium were found for all soft materials studied. Bond strength
      varied depending on the chemical basis of the soft material. Results indicated
      that maximal bond strengths were obtained by the combinations Supersoft with
      Super-Bond, Supersoft with subsequent silicoating, and bonding with Dentacolor
      connector. Few color shifts attributable to the titanium reinforcement were
      evident in the 2-mm layers of the soft materials applied. CONCLUSION: The results
      of this study showed that it is possible to combine a titanium framework and soft
      silicone materials.

PMID- 11319541
TI  - Use of a patient's old complete denture to determine vertical dimension of
      occlusion.

PMID- 11319540
TI  - Use of inductively coupled plasma-emission spectroscopy and mercury vapor
      analyses to evaluate elemental release from a high-copper dental amalgam: a pilot
      study.
AB  - STATEMENT OF PROBLEM: The use of dental amalgam as a direct restorative material
      has been a subject of controversy for many years. The potential safety of amalgam
      has been questioned because of leakage of elements such as mercury, copper, tin,
      and silver. PURPOSE: This study evaluated the elemental leaching from Tytin
      dental amalgam placed in deionized water for 2 months. Both mercury vapor and
      elemental (silver, copper, tin, and mercury) analyses were performed. MATERIAL
      AND METHODS: Two capsules of Tytin amalgam were triturated (one for the
      precipitate and liquid analysis, and the other for the mercury vapor analysis)
      and stored in a polypropylene tube with 10 mL deionized water for 60 days at room
      temperature. The amalgam pellet then was removed and rinsed with deionized water.
      The resulting liquid was separated from a precipitate, and 2 separate analyses
      were run: one on the liquid without any precipitate and another on the
      precipitate. Elemental analyses for copper (Cu), tin (Sn), mercury (Hg), and
      silver (Ag) were determined by inductively coupled plasma-emission spectroscopy
      with a Perkin-Elmer P2000 spectrometer. Mercury vapor analyses were performed
      daily for 60 days with a Jerome 431-X vapor analyzer. RESULTS: The maximum amount
      of copper (80 microg), silver (2.6 microg), mercury (15 microg), and tin (550
      microg) was found in the precipitate. The maximum amount of mercury vapor
      released was 67 microg/m(3)/d. CONCLUSION: Under the conditions of this in vitro
      study, there was a significant amount of elemental leaching and mercury vapor
      release from the Tytin amalgam over a 60-day period.

PMID- 11319542
TI  - Modification of a Super-Sep bottle for paint-on application of a separating
      medium used in flasking dentures.
AB  - Modifying a Super-Sep bottle by adding a brush to the lid for paint-on use allows
      for the precise application of the separating medium used when flasking dentures.
      Super-Sep offers many advantages over other commonly used separating mediums: It
      is virtually dimensionless, allowing for better accuracy; it dries quickly and
      functions best on moist stone; and it can be poured against immediately. The
      latter fact means less time is needed before the subsequent layers of stone can
      be applied when denture flasking.

PMID- 11319543
TI  - Fabricating a simple closure guide for the dual-arch impression technique.

PMID- 11319544
TI  - Technique for quick conversion of an obturator into a hollow bulb.

PMID- 11319545
TI  - Listening to postdocs.

PMID- 11319546
TI  - Do 'smart' mice feel more pain, or are they just better learners?

PMID- 11319548
TI  - Faces and places: of central (and peripheral) interest.

PMID- 11319549
TI  - Beam me up, Scottie! TREK channels swing both ways.

PMID- 11319550
TI  - Brain glucosensing and the K(ATP) channel.

PMID- 11319551
TI  - Representing retinal image speed in visual cortex.

PMID- 11319553
TI  - Regeneration of CNS axons back to their target following treatment of adult rat
      brain with chondroitinase ABC.

PMID- 11319554
TI  - Beyond parallel fiber LTD: the diversity of synaptic and non-synaptic plasticity
      in the cerebellum.
AB  - In recent years, it has become clear that motor learning, as revealed by
      associative eyelid conditioning and adaptation of the vestibulo-ocular reflex,
      contributes to the well-established cerebellar functions of sensorimotor
      integration and control. Long-term depression of the parallel fiber-Purkinje cell
      synapse (which is often called 'cerebellar LTD') is a cellular phenomenon that
      has been suggested to underlie these forms of learning. However, it is clear that
      parallel fiber LTD, by itself, cannot account for all the properties of
      cerebellar motor learning. Here we review recent electrophysiological experiments
      that have described a rich variety of use-dependent plasticity in cerebellum,
      including long-term potentiation (LTP) and LTD of excitatory and inhibitory
      synapses, and persistent modulation of intrinsic neuronal excitability. Finally,
      using associative eyelid conditioning as an example, we propose some ideas about
      how these cellular phenomena might function and interact to endow the cerebellar
      circuit with particular computational and mnemonic properties.

PMID- 11319555
TI  - Protein mobility and GABA-induced conformational changes in GABA(A) receptor pore
      lining M2 segment.
AB  - Protein movements underlying ligand-gated ion channel activation are poorly
      understood. Here we used disulfide bond trapping to examine the proximity and
      mobility of cysteines substituted for aligned GABAA receptor alpha1 and beta1 M2
      segment channel-lining residues in resting and activated receptors. With or
      without GABA, disulfide bonds formed at alpha1N275C/beta1E270C (20') and
      alpha1S272C/beta1H267C (17'), near the extracellular end, suggesting that this
      end is more mobile and/or flexible than the rest of the segment. Near the middle
      of M2, at alpha1T261C/beta1T256C (6'), a disulfide bond formed only in the
      presence of GABA and locked the channels open. Channel activation must involve an
      asymmetric rotation of two adjacent subunits toward each other. This would move
      aligned engineered cysteines on different subunits into proximity and allow
      disulfide bond formation without blocking conduction. Asymmetric rotation of M2
      segments is probably a common gating mechanism in other ligand-gated ion
      channels.

PMID- 11319556
TI  - KCNK2: reversible conversion of a hippocampal potassium leak into a voltage
      dependent channel.
AB  - Potassium leak channels are essential to neurophysiological function. Leaks
      suppress excitability through maintenance of resting membrane potential below the
      threshold for action potential firing. Conversely, voltage-dependent potassium
      channels permit excitation because they do not interfere with rise to threshold,
      and they actively promote recovery and rapid re-firing. Previously attributed to
      distinct transport pathways, we demonstrate here that phosphorylation of single,
      native hippocampal and cloned KCNK2 potassium channels produces reversible
      interconversion between leak and voltage-dependent phenotypes. The findings
      reveal a pathway for dynamic regulation of excitability.

PMID- 11319557
TI  - A candidate taste receptor gene near a sweet taste locus.
AB  - The mechanisms underlying sweet taste in mammals have been elusive. Although
      numerous studies have implicated G proteins in sweet taste detection, the
      expected G protein-coupled receptors have not been found. Here we describe a
      candidate taste receptor gene, T1r3, that is located at or near the mouse Sac
      locus, a genetic locus that controls the detection of certain sweet tastants.
      T1R3 differs in amino acid sequence in mouse strains with different Sac
      phenotypes ('tasters' versus 'nontasters'). In addition, a perfect correlation
      exists between two different T1r3 alleles and Sac phenotypes in recombinant
      inbred mouse strains. The T1r3 gene is expressed in a subset of taste cells in
      circumvallate, foliate and fungiform taste papillae. In circumvallate and foliate
      papillae, most T1r3-expressing cells also express a gene encoding a related
      receptor, T1R2, raising the possibility that these cells recognize more than one
      ligand, or that the two receptors function as heterodimers.

PMID- 11319558
TI  - The scaffold protein, Homer1b/c, regulates axon pathfinding in the central
      nervous system in vivo.
AB  - Homer proteins are a family of multidomain cytosolic proteins that have been
      postulated to serve as scaffold proteins that affect responses to extracellular
      signals by regulating protein-protein interactions. We tested whether Homer
      proteins are involved in axon pathfinding in vivo, by expressing both wild-type
      and mutant isoforms of Homer in Xenopus optic tectal neurons. Time-lapse imaging
      demonstrated that interfering with the ability of endogenous Homer to form
      protein-protein interactions resulted in axon pathfinding errors at stereotypical
      choice points. These data demonstrate a function for scaffold proteins such as
      Homer in axon guidance. Homer may facilitate signal transduction from cell
      surface receptors to intracellular proteins that govern the establishment of axon
      trajectories.

PMID- 11319559
TI  - ATP-sensitive K+ channels in the hypothalamus are essential for the maintenance
      of glucose homeostasis.
AB  - Glucose-responsive (GR) neurons in the hypothalamus are thought to be critical in
      glucose homeostasis, but it is not known how they function in this context.
      Kir6.2 is the pore-forming subunit of K(ATP) channels in many cell types,
      including pancreatic beta-cells and heart. Here we show the complete absence of
      both functional ATP-sensitive K+ (K(ATP)) channels and glucose responsiveness in
      the neurons of the ventromedial hypothalamus (VMH) in Kir6.2-/- mice. Although
      pancreatic alpha-cells were functional in Kir6.2-/-, the mice exhibited a severe
      defect in glucagon secretion in response to systemic hypoglycemia. In addition,
      they showed a complete loss of glucagon secretion, together with reduced food
      intake in response to neuroglycopenia. Thus, our results demonstrate that KATP
      channels are important in glucose sensing in VMH GR neurons, and are essential
      for the maintenance of glucose homeostasis.

PMID- 11319560
TI  - Joint-encoding of motion and depth by visual cortical neurons: neural basis of
      the Pulfrich effect.
AB  - Motion and stereoscopic depth are fundamental parameters of the structural
      analysis of visual scenes. Because they are defined by a difference in object
      position, either over time or across the eyes, a common neural machinery may be
      used for encoding these attributes. To examine this idea, we analyzed responses
      of binocular complex cells in the cat striate cortex to stimuli of various intra-
      and interocular spatial and temporal shifts. We found that most neurons exhibit
      space-time-oriented response profiles in both monocular and binocular domains.
      This indicates that these neurons encode motion and depth jointly, and it
      explains phenomena such as the Pulfrich effect. We also found that the
      relationship between neuronal tuning of motion and depth conforms to that
      predicted by the use of motion parallax as a depth cue. These results demonstrate
      a joint-encoding of motion and depth at an early cortical stage.

PMID- 11319561
TI  - Learning to see: experience and attention in primary visual cortex.
AB  - The response properties of neurons in primary sensory cortices remain malleable
      throughout life. The existence of such plasticity, and the characteristics of a
      form of implicit learning known as perceptual learning, suggest that changes in
      primary sensory cortex may mediate learning. We explored whether modification of
      the functional properties of primary visual cortex (V1) accompanies perceptual
      learning. Basic receptive field properties, such as location, size and
      orientation selectivity, were unaffected by perceptual training, and visual
      topography (as measured by magnification factor) was indistinguishable between
      trained and untrained animals. On the other hand, the influence of contextual
      stimuli placed outside the receptive field showed a change consistent with the
      trained discrimination. Furthermore, this property showed task dependence, only
      being manifest when the animal was performing the trained discrimination.

PMID- 11319562
TI  - Speed skills: measuring the visual speed analyzing properties of primate MT
      neurons.
AB  - Knowing the direction and speed of moving objects is often critical for survival.
      However, it is poorly understood how cortical neurons process the speed of image
      movement. Here we tested MT neurons using moving sine-wave gratings of different
      spatial and temporal frequencies, and mapped out the neurons' spatiotemporal
      frequency response profiles. The maps typically had oriented ridges of peak
      sensitivity as expected for speed-tuned neurons. The preferred speed estimate,
      derived from the orientation of the maps, corresponded well to the preferred
      speed when moving bars were presented. Thus, our data demonstrate that MT neurons
      are truly sensitive to the object speed. These findings indicate that MT is not
      only a key structure in the analysis of direction of motion and depth perception,
      but also in the analysis of object speed.

PMID- 11319563
TI  - Center-periphery organization of human object areas.
AB  - The organizing principles that govern the layout of human object-related areas
      are largely unknown. Here we propose a new organizing principle in which object
      representations are arranged according to a central versus peripheral visual
      field bias. The proposal is based on the finding that building-related regions
      overlap periphery-biased visual field representations, whereas face-related
      regions are associated with center-biased representations. Furthermore, the
      eccentricity maps encompass essentially the entire extent of object-related
      occipito-temporal cortex, indicating that most object representations are
      organized with respect to retinal eccentricity. A control experiment ruled out
      the possibility that the results are due exclusively to unequal feature
      distribution in these images. We hypothesize that brain regions representing
      object categories that rely on detailed central scrutiny (such as faces) are more
      strongly associated with processing of central information, compared to
      representations of objects that may be recognized by more peripheral information
      (such as buildings or scenes).

PMID- 11319564
TI  - Musical syntax is processed in Broca's area: an MEG study.
AB  - The present experiment was designed to localize the neural substrates that
      process music-syntactic incongruities, using magnetoencephalography (MEG).
      Electrically, such processing has been proposed to be indicated by early right
      anterior negativity (ERAN), which is elicited by harmonically inappropriate
      chords occurring within a major-minor tonal context. In the present experiment,
      such chords elicited an early effect, taken as the magnetic equivalent of the
      ERAN (termed mERAN). The source of mERAN activity was localized in Broca's area
      and its right-hemisphere homologue, areas involved in syntactic analysis during
      auditory language comprehension. We find that these areas are also responsible
      for an analysis of incoming harmonic sequences, indicating that these regions
      process syntactic information that is less language-specific than previously
      believed.

PMID- 11319565
TI  - Effect of subjective perspective taking during simulation of action: a PET
      investigation of agency.
AB  - Perspective taking is an essential component in the mechanisms that account for
      intersubjectivity and agency. Mental simulation of action can be used as a
      natural protocol to explore the cognitive and neural processing involved in
      agency. Here we took PET measurements while subjects simulated actions with
      either a first-person or a third-person perspective. Both conditions were
      associated with common activation in the SMA, the precentral gyrus, the precuneus
      and the MT/V5 complex. When compared to the first-person perspective, the third
      person perspective recruited right inferior parietal, precuneus, posterior
      cingulate and frontopolar cortex. The opposite contrast revealed activation in
      left inferior parietal and somatosensory cortex. We suggest that the right
      inferior parietal, precuneus and somatosensory cortex are specifically involved
      in distinguishing self-produced actions from those generated by others.

PMID- 11319566
TI  - A federal solution a regulation for all.

PMID- 11319567
TI  - Effects of fosinopril or sustained-release verapamil on blood pressure and serum
      catecholamine concentrations in elderly hypertensive men.
AB  - A randomized, double-blind, placebo-controlled clinical trial showed 14 of 18
      (78%) of the elderly hypertensive men in this study had an uncomplicated and
      beneficial response to either fosinopril or verapamil. There was a well-tolerated
      reduction in systolic blood pressure (SBP) and diastolic blood pressure (DRP).
      There were no significant adverse drug events. Only the sitting SBP and the
      sitting DBP were significantly lowered by fosinopril and verapamil SR. Because
      reduction in both SBP and DBP in elderly hypertensives has been shown to be
      beneficial, these findings take on further importance when considering the choice
      of medication for antihypertensive therapy in the elderly. The increase in
      norepinephrine in the fosinopril-treated patients may explain why patients
      treated with long-term angiotensin-converting enzyme inhibitors alone or in
      combination with diuretics rarely complain of orthostatic symptoms.

PMID- 11319568
TI  - Effect of temperature on binding characteristics of phenytoin to serum proteins
      in monotherapy adult patients with epilepsy.
AB  - The effects of temperature on binding characteristics of phenytoin (PHT) to serum
      proteins were determined in adult patients with epilepsy. Serum samples examined
      in the study were obtained from 47 adult patients (29 men, 18 women) with
      epilepsy on PHT monotherapy. Ages ranged from 18 to 64 years (mean [SD], 36.8
      [12.1] years). Protein binding of PHT was evaluated by ultrafiltration under
      current laboratory routine conditions (25 +/- 3 degrees C) or at a temperature of
      37 degrees C. The in vivo binding parameters of PHT to serum proteins were
      determined using a binding equation derived from the Scatchard equation for a one
      site binding model. Significant differences were observed in serum concentrations
      of unbound PHT between paired data (P <.05). The mean association constants (K)
      of PHT to serum proteins are 0.009 L micromol(-1) at 25 +/- 3 degrees C and 0.003
      L micromol(-1) at 37 degrees C, whereas mean total concentrations of binding
      sites [n(Pt)] are 1215 micromol L(-1) for 25 +/- 3 degrees C and 2263 micromol L(
      1) for 37 degrees C. Significant differences were observed in binding
      characteristics of PHT to serum proteins between the data determined in different
      conditions of ultrafiltration (P <.05). Our study confirms that binding affinity
      for PHT-serum protein interaction is approximately 67% lower at 37 degrees C than
      at 25 +/- 3 degrees C, and, consequently, binding potential [K.n(Pt)] is
      approximately 38% lower at 37 degrees C than at 25 +/- 3 degrees C.

PMID- 11319569
TI  - Improved efficacy and safety of controlled-release diltiazem compared to
      nifedipine may be related to its negative chronotropic effect.
AB  - The objective of this study was to assess the safety and efficacy of long-acting
      preparations of two commonly used calcium antagonists with particular reference
      to their effects on heart rate. Twenty patients with chronic stable angina were
      recruited to a double-blind, double-dummy crossover study of controlled-release
      diltiazem (diltiazem CR) versus sustained-release nifedipine (nifedipine SR) and
      underwent clinical assessment, symptom and adverse event reporting, and repeated
      treadmill exercise tests over a 10- to 11-week period. The main outcome measures
      were heart rate at rest and exercise, incidence of angina and nitroglycerin use,
      treadmill exercise performance (duration, time to angina, time to 1-mm ST-segment
      depression, heart rate at equivalent maximal exercise, and maximal ST-segment
      depression), and adverse events. Diltiazem CR significantly reduced heart rate at
      rest and equivalent exercise and incidence of angina and nitroglycerin use
      compared with nifedipine SR. Exercise duration time to angina and time to 1-mm ST
      segment depression (but not maximal ST-segment depression) were all significantly
      improved by diltiazem CR. Diltiazem CR also caused significantly fewer adverse
      events than nifedipine SR. Calcium antagonists with negative chronotropic effects
      (eg, diltiazem CR) are safer and more efficacious as monotherapy in chronic
      stable angina than dihydropyridines (eg, nifedipine SR) even when a long-acting
      formulation of the latter is used.

PMID- 11319570
TI  - University of Miami Division of Clinical Pharmacology Therapeutic Rounds: the
      water-intolerant patient and perioperative hyponatremia.
AB  - Perioperative hyponatremia has been recognized as a serious in-hospital
      complication for many years. Because the kidney responds to changes in
      extracellular fluid tonicity by adjusting water excretion, a defect in any of
      several key elements of water excretion can lead to water retention and
      hyponatremia. Most cases of hyponatremia are caused by impaired renal water
      excretion in the presence of continued water intake. For the kidney to excrete
      excess free water and thereby protect the extracellular fluid against
      hyponatremia, there must be an adequate glomerular filtration rate (GFR),
      adequate delivery of glomerular filtrate to the diluting segments of the distal
      nephron, intact tubular diluting mechanisms, and appropriate inhibition of
      antidiuretic hormone (ADH) synthesis and release. Virtually all of the clinical
      disorders producing hyponatremia are based on abnormalities of these few
      mechanisms of water regulation. Finding the reason for impaired renal water
      excretion is the key to diagnosing the cause of hyponatremia. Impaired renal
      water excretion may be caused by impaired GFR (renal failure), impaired water
      delivery to the diluting segments of the distal nephron because of increased
      proximal reabsorption (decreased extracellular fluid volume and edematous
      states), impaired renal diluting mechanism (thiazide diuretics), the syndrome of
      inappropriate ADH (SIADH) due to a variety of causes including the perioperative
      state, and hypothyroidism or adrenal insufficiency. Any of the states that impair
      water excretion can produce hyponatremia in a patient with an initially normal
      serum sodium concentration if sufficient free water is supplied. Therefore, a
      patient who has one of the conditions listed above, including the perioperative
      state, may be considered "water intolerant" even if the serum sodium is normal.
      Such a patient is at risk for developing severe hyponatremia if given hypotonic
      IV fluids or a large oral water load. An understanding of the basic mechanisms
      leading to impaired water excretion and "water intolerance" is therefore an
      important key to avoiding perioperative hyponatremia.

PMID- 11319571
TI  - The management challenges of chronic pain: the role of antidepressants.
AB  - Chronic pain is both difficult for patients to tolerate and for clinicians to
      treat effectively. It differs from other types of pain in etiology and impact,
      which in turn affects the duration and modalities of treatment options. Forty
      years of research have confirmed the efficacy of antidepressant agents in the
      management of chronic pain, yet these agents are used inadequately. A significant
      amount of evidence supports the use of the traditional tricyclic antidepressants
      (TCAs) in the management of chronic pain, but because of their acute synaptic
      effects on multiple, nontherapeutic receptor systems, they are associated with
      numerous undesirable side effects. The newer selective serotonin reuptake
      inhibitors (SSRIs) have, comparatively, only serotonin-receptor-mediated side
      effects. These agents have not been thoroughly studied in the treatment of
      chronic pain. Moreover, because SSRIs impact reuptake of only one monoamine
      system, it is plausible that they may be less efficacious than the TCAs in
      treating chronic pain. Venlafaxine, the first agent in the new class of serotonin
      (5-HT)-norepinephrine (NE) reuptake inhibitors, is unique because it inhibits
      reuptake of both 5-HT and NE (and to a lesser extent dopamine), as do some of the
      TCAs; however, it accomplishes this without affecting other nontherapeutic
      receptors. Venlafaxine is at least as effective as the TCAs, but is more
      tolerable, because it lacks the receptor-mediated side effects common to the
      TCAs. The unique characteristics of venlafaxine, including minimal cytochrome P
      450 drug interaction, may make it a particularly useful antidepressant in the
      adjunctive treatment of chronic pain.

PMID- 11319572
TI  - What's gone wrong with clinical research.

PMID- 11319573
TI  - The position of paracetamol in the world of analgesics.

PMID- 11319574
TI  - Recommending analgesics for people with asthma.
AB  - Asthma is a common condition, affecting approximately 7% of people worldwide.
      However, the prevalence varies among countries, and in Australia, asthma affects
      10% of adults and approximately 20% of children. For some of these patients,
      ingredients in some over-the-counter analgesics may pose problems. Aspirin
      sensitivity, defined as urticaria, angioedema, or rhinitis after aspirin
      ingestion, affects only 0.3% of the general population. However, certain patient
      groups, such as asthmatics, are at an increased risk, with reports of an
      incidence as high as 20% in this patient population. This phenomenon is not
      restricted to aspirin, as all nonsteroidal anti-inflammatory drugs (NSAIDs) that
      inhibit the enzyme cyclooxygenase display a high incidence of cross-sensitivity.
      In contrast, paracetamol (acetaminophen) is well tolerated by the majority of
      people with asthma and is seldom associated with cross-sensitivity. Determining
      who is likely to be affected is difficult because the sequence of symptoms is
      hard to predict, and patients often do not associate an asthma attack with the
      use of aspirin or an NSAID. The only definitive way to diagnose sensitivity is by
      provocation tests. In view of these difficulties, it is important for health care
      practitioners to take a pro-active stance by asking questions to determine
      whether aspirin sensitivity is a problem, counseling people about the risks, and
      helping them make an appropriate analgesic choice.

PMID- 11319575
TI  - Renal and related cardiovascular effects of conventional and COX-2-specific
      NSAIDs and non-NSAID analgesics.
AB  - On a daily basis it appears that as many as one in five adults in the United
      States may consume an analgesic compound either on a prescription basis or by
      over-the-counter (OTC) purchase. This high profile of intermittent or repetitive
      analgesic use appears to be relatively similar throughout the developed world.
      Although analgesics generally have a good renal safety profile, the nonsteroidal
      anti-inflammatory drug (NSAID) analgesics may produce mild renal side effects,
      such as the generation of peripheral edema in up to 5% of the general population.
      Other more serious renal and related cardiovascular side effects tend to be more
      apparent in lesser numbers of clinically "at risk" NSAID analgesic users. In
      contrast, non-NSAID analgesics, such as paracetamol or tramadol, have essentially
      no renal or related cardiovascular side effects when used at recommended dosing
      schedules. This review characterizes the renal syndromes associated with the use
      of NSAID analgesics, identifies the risks inherent in the use of these compounds
      in treated patients with hypertension and congestive heart failure, summarizes
      the early comparable data available for the new COX-2-specific inhibitors, and
      profiles the scant acute and long-term clinical concerns attendant with the use
      of non-NSAID nonnarcotic analgesics. It is important that healthcare providers
      and practitioners are aware of the relative renal risks of different analgesics
      and that they use this knowledge to counsel the analgesic-consuming population
      appropriately.

PMID- 11319576
TI  - The role of analgesics in the management of osteoarthritis pain.
AB  - Osteoarthritis (OA), previously called degenerative joint disease, is a common
      condition. Figures from the United States indicate that as many as 80% of the
      population has radiographic evidence of this disease by the age of 65 years, and
      difficulty with ambulation, mostly attributable to OA, accounts for as many as
      30% of all visits to a doctor. There is no known cure for OA and hence treatments
      are used to reduce pain and other symptoms, maintain and/or improve joint
      mobility, and limit functional disability, with the overall management goal of
      improving the patients' quality of life. To this point, one of the key objectives
      of treatment is to manage knee pain. In the past, treatment was most often
      initiated with the prescription of nonsteroidal anti-inflammatory drugs (NSAIDs).
      However, evidence that (1) NSAIDs offer no additional symptomatic benefit over
      simple analgesics, such as paracetamol (acetaminophen), for many patients with
      OA, (2) NSAID-related adverse gastrointestinal (GI) effects are a significant
      cause or morbidity and mortality, and (3) NSAIDs could have a possible
      deleterious effect on articular cartilage metabolism, has led to a change in
      management strategy. Contemporary thinking is that nonpharmacologic measures
      should be tried first, with pharmacologic intervention used as an adjunct.
      Nonpharmacologic therapy includes such things as patient education, weight loss,
      physical therapy, occupational therapy, and exercise. Paracetamol, in doses of as
      high as 4000 mg/day, is the first-line drug of choice for the management of the
      pain of OA. If the patient does not respond to paracetamol, NSAIDs may be an
      appropriate alternative, provided they are not medically contraindicated. Because
      of their GI toxicity, it is suggested that NSAIDs be used in the lowest possible
      dose for the shortest possible time. In OA, the intensity of pain varies both
      during the day and night, enabling the use of NSAIDs with a short half-life on an
      as-needed basis. Strategies to reduce the risk of NSAID-related GI complications
      include prophylaxis with misoprostol. Current developments in the field of OA
      management are also discussed, including the emergence of drugs that specifically
      inhibit cyclooxygenase 2 (COX-2) and disease-modifying treatments.

PMID- 11319577
TI  - Exploring the link between gastrointestinal complications and over-the-counter
      analgesics: current issues and considerations.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the most widely used
      classes of drug worldwide, with as many as 8% of the global adult population
      taking prescription NSAIDs at any given time. It is well documented that NSAID
      related gastrointestinal (GI) effects are a significant cause of morbidity and
      mortality. Data from Australia alone suggest that each year there may be as many
      as 2300 serious GI complications and 300 deaths. Risk factors for NSAID-related
      GI complications have been established and can be broadly divided into two
      groups: uncontrollable factors, which include elements such as age, gender,
      comorbidity, and a history of GI conditions, and controllable factors, such as
      the dose, type, and duration of NSAID treatment and cotherapy and possibly
      Helicobacter pylori infection. The increasing trend toward self-medication raises
      questions about the potential for GI complications with OTC doses of NSAIDs.
      Although there is some evidence that the frequency of GI complications with OTC
      doses may be less than that seen with prescription doses, it still exists. At
      present, there is insufficient evidence to determine the population attributable
      risk associated with their widespread use. Emerging data and factors that
      confound their interpretation are discussed. Given that the data are limited, a
      clear picture of the true extent of GI complications with OTC NSAIDs is not yet
      available. In light of our current understanding and because paracetamol
      continues to demonstrate a favorable side-effect profile, it remains a first-line
      analgesic for everyday pain.

PMID- 11319578
TI  - Therapeutic misadventure with paracetamol: fact or fiction?
AB  - As a consequence of its consistent safety profile and the low incidence of side
      effects, paracetamol is one of the most widely used analgesics, both in adults
      and children. However, paracetamol has the potential for hepatotoxicity, usually
      as a result of deliberate self-poisoning or, to a much lesser extent, accidental
      overdose. A variety of factors is thought to influence hepatotoxicity, including
      dose, concomitant use of microsome-inducing agents and other drugs, underlying
      disease, malnutrition, fasting, acute and chronic alcohol intake, ethnicity, and
      age. Unfortunately, none of these factors has been properly studied in humans.
      From a physiological standpoint, acute paracetamol hepatotoxicity at therapeutic
      doses is extremely unlikely despite reports of so-called therapeutic
      misadventure. It is clear that, in many of these cases, grossly excessive doses
      of paracetamol have been taken. Analyzing the various reports is difficult as the
      data are often incomplete. In summary, although hepatic toxicity is recognized in
      patients taking a major paracetamol overdose, the incidence of adverse events
      with its proper use is very low, particularly when considering with the enormous
      volume of drug use. Therapeutic misadventure is extremely uncommon and the facts
      are often misrepresented.

PMID- 11319579
TI  - Gastrointestinal complications of prescription and over-the-counter nonsteroidal
      anti-inflammatory drugs: a view from the ARAMIS database. Arthritis, Rheumatism,
      and Aging Medical Information System.
AB  - More than 30 million people worldwide consume prescription nonsteroidal anti
      inflammatory drugs (NSAIDs) on a daily basis. Gastrointestinal (GI) toxicity
      owing to the use of NSAIDs is a well-recognized clinical problem, with
      approximately 25% of all reported adverse drug reactions being attributed to
      prescription NSAID use. In addition to prescription NSAIDs, the use of over-the
      counter (OTC) formulations of these products is common. Although it has been
      suggested that OTC doses of NSAIDs may not lead to significant GI toxicity, the
      data confirming this have been lacking. Data on the GI risks of OTC doses of
      aspirin, ibuprofen, naproxen, paracetamol, and no drug from 4164 consecutively
      diagnosed patients with rheumatoid arthritis from eight ARAMIS (Arthritis,
      Rheumatism, and Aging Medical Information System) centers in North America are
      presented. Serious GI events were defined as GI bleeds and other clinically
      significant GI events requiring hospitalization. Relative risks were standardized
      for potential demographic confounders using Cox proportional hazard models.
      Although the relative risk of OTC doses of NSAIDs (3 to 4) is less than the
      previously published risk of prescription doses (6 to 7), it remains clinically
      significant and a matter of serious concern because of the widespread use of
      these medications and an underappreciation of the true risk. Paracetamol was not
      associated with increased risk of GI complications and should be considered first
      line therapy.

PMID- 11319580
TI  - Treatment of pain or fever with paracetamol (acetaminophen) in the alcoholic
      patient: a systematic review.
AB  - An unexpected clinical question has emerged in the treatment of pain or fever in
      the alcoholic patient: Is paracetamol a safe medication for the alcoholic
      patient? After decades of use in a variety of patients, sporadic reports suggest
      a relationship between liver injury and the use of paracetamol by alcoholic
      patients. We performed a systematic review of the medical literature to answer
      the question: Can administration of therapeutic doses of paracetamol cause
      hepatic injury in the alcoholic patient? After extensive data retrieval, each
      article in any language that involved the use of paracetamol by an alcoholic
      patient was abstracted and categorized for strength of evidence. Class I data
      (randomized, controlled trials) show that repeated ingestion of a therapeutic
      dose of paracetamol over 48 hours by patients with severe alcoholism did not
      produce an increase in hepatic aminotransferase enzyme levels nor any clinical
      manifestations compared with a placebo group. Class II data (prospective,
      nonrandomized trials) reveal that therapeutic doses of paracetamol have been
      administered to patients and an array of liver diseases (alcoholic, primary
      biliary, postnecrotic, or unspecified cirrhosis or alcoholic, acute viral,
      chronic active, or other infectious hepatitis) for periods up to 14 days without
      adverse effect. Finally, in several studies, a 1- to 2-g single dose of
      paracetamol was administered to alcoholic patients to study metabolism, again
      without adverse effect. In contrast, Class III data (retrospective case reviews
      and case reports) describe hepatic injury after repeated paracetamol ingestion
      with therapeutic intent, although usually not at therapeutic doses.
      Unfortunately, the information contained in Class III reports is often incomplete
      and contradictory. The history of ingestion is often unknown or contradicts other
      clinical information provided. For example, the history may indicate a
      therapeutic dose, but the serum paracetamol is elevated to levels only produced
      by ingestion much larger than the history indicates. In summary, all
      methodologically sound studies available indicate that therapeutic dosing of
      paracetamol to the alcoholic patient is not associated with hepatic injury. In
      fact, there is no change at all in hepatic aminotransferase enzymes, prothrombin
      time, or other biochemical parameters when compared with a placebo group in well
      designed trials. Unless stronger evidence of a potentially dangerous interaction
      emerges, the use of paracetamol in the alcoholic patient is reasonable. During
      chronic treatment of pain, paracetamol may be preferred in the compliant
      alcoholic patients owing to the adverse effects associated with long-term use of
      nonsteroidal anti-inflammatory agents.

PMID- 11319581
TI  - Paracetamol efficacy and safety in children: the first 40 years.
AB  - Paracetamol (acetaminophen) has a unique role in children because it is the first
      line choice for the treatment of both fever and pain. When used in the
      recommended doses, it has few side effects and is remarkably well tolerated.
      While fever alone requires no treatment, when associated with discomfort or pain,
      paracetamol offers relief. Also, for mild to moderate pain, paracetamol, either
      alone or in combination with another drug, is effective. Even in severe pain,
      paracetamol offers a significant additive analgesic effect to opiates. Globally,
      the pediatric dose varies between 10 and 15 mg/kg. In the United Kingdom, 10
      mg/kg is given every 4 hours, up to a maximum of four doses per day; in
      Australia, 15 mg/kg is administered 4-hourly up to a total dose of 60 mg/kg/day.
      In overdose, paracetamol is hepatotoxic. Single ingestions of more than ten times
      the recommended dose are potentially toxic. The development of specific antidotes
      and the universal availability of the Rumack-Matthew Nomogram have made the early
      treatment of overdose effective without long-term sequelae. There are sporadic
      case reports of chronic overdosing resulting in liver failure. Although the
      specific predictors are still being defined, exposures greater than 140 mg/kg/day
      for several days carry a risk of serious toxicity. In children, aspirin use has
      almost disappeared with the concurrent decline in Reye Syndrome. Less clinical
      experience has accumulated with ibuprofen, and it remains the second-line
      treatment for fever and pain. In conclusion, paracetamol remains the first-choice
      over-the-counter treatment for analgesia and antipyresis in children.

PMID- 11319582
TI  - Paracetamol: past, present, and future.
AB  - Paracetamol (acetaminophen) is one of the most widely used of all drugs, with a
      wealth of experience clearly establishing it as the standard antipyretic and
      analgesic for mild to moderate pain states. First used clinically by von Mering
      in 1893, paracetamol did not appear commercially until 1950 in the United States
      and 1956 in Australia. During the 1960s and 1970s, increasing concern was raised
      about the toxicity of nonprescription analgesics, but in normal use paracetamol
      exhibited a consistent safety profile. Its exemplary safety record was marred by
      the discovery in 1966 that a major overdose could be complicated by severe and
      sometimes fatal liver damage. Fortunately, early treatment with N-acetylcysteine
      prevents liver toxicity. A turning point in the choice of pediatric analgesic
      came in the 1980s when aspirin was linked to Reye's syndrome. As a consequence,
      paracetamol became the mainstay analgesic and antipyretic for children with a
      subsequent reduction in the incidence of Reye's syndrome. Currently, paracetamol
      is a first-line choice for pain management and antipyresis in a variety of
      patients, including children, pregnant women, the elderly, those with
      osteoarthritis, simple headaches, and those with noninflammatory musculoskeletal
      conditions. With proper use, paracetamol seldom causes adverse events and reports
      of serious side effects are rare. It has a broad tolerability and is of
      particular value in the treatment of patients in whom nonsteroidal anti
      inflammatory drugs are contraindicated such as aspirin-sensitive asthmatics and
      people at risk of gastrointestinal complications. In the future, a better insight
      into the mechanism of action of paracetamol may be gained from a fuller
      understanding of the cyclooxygenase enzymes. In the meantime, paracetamol may
      find applications in other therapeutic areas, such as the prevention of
      atherosclerosis via a potential antioxidant activity. In summary, although it is
      more than a century since the first clinical use of paracetamol, it continues to
      be a first-line therapy of choice in adults and children with fever and pain. In
      addition, current research suggests that paracetamol may have a much broader
      clinical utility in years to come.

PMID- 11319583
TI  - Monoclonal antibodies and autologous stem cell transplantation for lymphoma.
AB  - The introduction of monoclonal antibodies into the clinic has paved the way for
      new approaches to stem cell transplantation for patients with lymphoma. These
      approaches include the development of new high-dose regimens with radiolabeled
      antibodies, in vivo purging techniques with the unlabeled antibodies, and post
      transplant adjuvant immunotherapy. Numerous trials have demonstrated the
      feasibility of these approaches. However, questions remain regarding the
      application of these antibodies including the ultimate efficacy. The recent
      results of the incorporation of monoclonal antibodies into stem cell
      transplantation and current research directions are reviewed.

PMID- 11319584
TI  - Megatherapy combining I(131) metaiodobenzylguanidine and high-dose chemotherapy
      with haematopoietic progenitor cell rescue for neuroblastoma.
AB  - Despite the use of aggressive chemotherapy, stage 4 high risk neuroblastoma still
      has very poor prognosis which is estimated at 25%. Metabolic radiotherapy with
      I(131) MIBG appears a feasible option to enhance the effects of chemotherapy.
      Seventeen patients having MIBG-positive residual disease received 4.1-11.1 mCi/kg
      of I(131) MIBG 7-10 days before initiating the high-dose chemotherapy cycle
      consisting of busulphan 16 mg/kg and melphalan 140 mg/m(2) followed by PBSC
      infusion. We compared the toxicity in these patients to that seen in 15 control
      subjects with neuroblastoma who underwent a PBSC transplant without MIBG therapy.
      We observed greater toxic involvement of the gastrointestinal system in children
      treated with I(131) MIBG: grade 2 or 3 mucositis developed in 13/17 patients
      treated with I(131) MIBG and in 9/15 treated without it. Grade 1-2
      gastrointestinal toxicity occurred in 12/17 children given MIBG and in 5/15 of
      the controls. One child receiving I(131) MIBG developed transient interstitial
      pneumonia. Another child who also received I(131) MIBG after PBSC rescue
      developed fatal pneumonia after the third course of metabolic radiotherapy. Our
      experience indicates that MIBG can be included in the high-dose chemotherapy
      regimens followed by PBSC rescue for children with residual neuroblastoma taking
      up MIBG. Attention should be paid to avoiding lung complications. Prospective
      studies are needed to demonstrate the real efficacy of this treatment.

PMID- 11319585
TI  - Influence of CD34(+) marrow cell dose on outcome of HLA-identical sibling
      allogeneic bone marrow transplants in patients with chronic myeloid leukaemia.
AB  - In order to study the influence of bone marrow CD34(+) cell dose on the outcome
      of allogeneic bone marrow transplantation (BMT), we analysed the results of BMT
      from HLA-identical siblings donors in 50 patients with chronic myeloid leukaemia
      (CML). The median numbers of nucleated cells (NC) and CD34(+) cells infused were
      2.18 x 10(8)/kg (0.05-4.14 x 10(8)/kg) and 3.12 x 10(6)/kg (0.35-8.52 x
      10(6)/kg), respectively. All patients engrafted. In univariate analysis, there
      was no correlation between the number of CD34(+) cells infused and the time to
      neutrophil recovery (P = 0.17). The Kaplan-Meier estimate of grade II-IV acute
      graft-versus-host disease (GVHD) at day 100 was 53 +/- 14% and 2-year survival
      was 46 +/- 15%. A number of CD34(+) cells infused greater than the median was the
      main factor increasing survival (P = 0.0006) and decreasing 100 day transplant
      related mortality (P = 0.009). Patient-, disease- and transplant-related
      characteristics were not statistically different among patients receiving more or
      less than the median number of CD34(+) cells. The rate of infectious deaths was
      significantly higher in patients receiving less than 3.12 x 10(6) CD34/kg (48% vs
      16%, P = 0.01). In a multivariable analysis, two factors associated with
      increased risk of death were advanced disease status at transplant (HR: 2.5 (95%
      CI: 1.09-5.75), P = 0.03) and a lower number of marrow CD34(+) cells infused/kg
      (HR: 4.55 (95% CI: 1.87-10.90), P = 0.0008).

PMID- 11319586
TI  - Non-HLA barriers to unrelated donor stem cell transplantation.
AB  - A prospective survey involving 544 searches of the US National Marrow Donor
      Program (NMDP) Registry was conducted to identify reasons why many patients who
      have apparent HLA-matched donors do not proceed to transplant. Coordinators at
      NMDP transplant centers, patients and referring physicians were surveyed shortly
      after the initial search, and follow-up surveys were sent to the coordinators as
      the search was ongoing. The death of the patient, worsening of the patient's
      medical condition and length of the search process were the most commonly cited
      barriers to transplantation. Other times a decision was made not to transplant
      through the NMDP due to the use of a donor from another source, a preference for
      chemotherapy or immunotherapy, hesitancy on the part of the transplant physician
      or patient, or because the patient did not require a transplant. Responses
      differed between U.S. and international cases. An unrelated donor outside the
      NMDP was the most common reason cited by international coordinators (46%),
      whereas the death of the patient was the most common reason among US coordinators
      (13%). The death of the patient was the second most common reason cited by
      international coordinators at 9%. Financial problems were listed by 41% of US
      coordinators as a potential barrier at the time of initial search, but only 5%
      indicated this as an actual barrier on a follow-up survey. Finances were cited as
      the most important reason 3% of the time overall, and 6% for African Americans
      and Asian/Pacific Islanders.

PMID- 11319587
TI  - Successful unrelated donor bone marrow transplantation for paroxysmal nocturnal
      hemoglobinuria.
AB  - Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal disease of
      hematopoiesis due to a mutation in the PIG-A gene. Affected patients may
      demonstrate hemolysis or venous thrombosis, and may develop MDS or aplastic
      anemia. Successful results may be obtained after conditioning and transplantation
      from syngeneic or genotypically matched sibling donors. Experience with
      transplantation from matched unrelated donors (MUD) is limited to eight patients,
      with only one survivor. We report three patients who underwent successful MUD BMT
      for PNH. All three patients had severe aplastic anemia (SAA) and PNH at the time
      of BMT. Unrelated donors were six-antigen HLA-matched (n = 2) or HLA-A mismatched
      (n = 1). Conditioning consisted of cytarabine, cyclophosphamide, TBI, and ATG.
      Grafts were T cell-depleted by anti-CD6/CD8 antibodies + complement. Further GVHD
      prophylaxis consisted of cyclosporine. Patients received 0.7-1.1 x 10(8)
      nucleated cells/kg and 1.1-2.1 x 10(6) CD34(+) cells/kg. Neutrophil engraftment
      occurred at 16-21 days. One patient developed grade 1 acute GVHD. Although all
      three patients experienced significant transplant-related complications, they
      ultimately resolved and all patients are alive and well 30-62 months after BMT. T
      cell-depleted MUD BMT is an effective treatment option for PNH-related MDS and
      SAA.

PMID- 11319588
TI  - Efficacy of high-dose therapy and autologous hematopoietic stem cell
      transplantation for non-Hodgkin's lymphoma in adults 60 years of age and older.
AB  - High-dose therapy (HDT) with autologous stem cell transplantation (ASCT) is the
      optimal treatment for patients with relapsed aggressive non-Hodgkin's lymphoma
      (NHL). HDT, however, is often reserved for relatively younger patients due to
      limited data in older adults. We treated 53 patients aged 60 years and older
      (median age 62 years, range 60.3-67.7 years) with HDT and ASCT for NHL at our
      centers. Forty-four patients (83%) had aggressive histology, 75% had
      chemosensitive disease and all had failed anthracycline therapy. Conditioning
      regimens included busulfan, melphalan, and thiotepa (45%); cyclophosphamide (CY),
      etoposide (VP-16), and total body irradiation (TBI) (30%); CY and TBI (15%); and
      other regimens (10%). Estimated 4-year overall survival (OS), progression-free
      survival, and treatment-related mortality (TRM) were 33%, 24% and 22%,
      respectively. A multivariable analysis demonstrated that patients with
      chemosensitive disease (P = 0.03) and < or =3 prior regimens (P = 0.03) had
      superior survival. Four-year OS in patients with chemosensitive disease was 39%
      vs 15% in patients with chemoresistant disease. Reduced TRM was associated with
      the CY, VP-16 and TBI regimen (P = 0.02). HDT therapy with ASCT may result in
      prolonged survival and potential cure for about a quarter of elderly patients,
      and for almost 40% with chemosensitive disease. Optimal conditioning regimen
      selection may further improve outcome by reducing TRM. Age alone should not be
      used to exclude patients from receiving myeloablative therapy with ASCT.

PMID- 11319589
TI  - Human gammadelta(+) T lymphocytes have in vitro graft vs leukemia activity in the
      absence of an allogeneic response.
AB  - Refractory acute lymphoblastic leukemia (ALL) is often incurable, and relapse
      rates following allogeneic bone marrow transplantation (BMT) remain high. We have
      reported that patients who develop increased numbers of gammadelta(+) T cells
      soon after BMT are significantly less likely to relapse. We now show in seven
      donor/recipient pairs that donor-derived Vdelta1(+)CD4(-)CD8(-)gammadelta(+) T
      cells are activated and proliferate in response to recipient primary ALL blasts.
      In addition, these cells have been shown to bind and lyse the recipient ALL
      blasts. Separately, gammadelta(+) T cells proliferate poorly or not at all in
      mixed lymphocyte culture against HLA-mismatched unrelated stimulator cells. These
      observations suggest that allogeneic gammadelta(+) T cells could be an effective
      immunotherapeutic strategy against refractory disease without the risk of graft
      versus-host disease.

PMID- 11319590
TI  - Extensive clonal expansion of T lymphocytes causes contracted diversity of
      complementarity-determining region 3 and skewed T cell receptor repertoires after
      allogeneic hematopoietic cell transplantation.
AB  - We previously described skewed repertoires of the T cell receptor-beta chain
      variable region (TCRBV) and the TCR-alpha chain variable region (TCRAV) soon
      after allogeneic hematopoietic cell transplantation. To determine the
      characteristics of skewed TCRBV after transplantation, we examined the clonality
      of T lymphocytes carrying skewed TCRBV subfamilies and determined the CDR3
      sequences of expanded T cell clones. In all 11 recipients examined, TCR
      repertoires were skewed, with an increase of certain TCRBV subfamilies that
      differed among individuals. In nine of 11 patients, clonal/oligoclonal T cell
      expansion was observed, although the expanded T cells were not necessarily
      oligoclonal. The extent of expansion after transplantation appeared to predict
      clonality. The arginine (R)-X-X-glycine (G) sequence was identified in clonally
      expanded T cells from four of five recipients examined, and glutamic acid (E),
      aspartic acid (D) and alanine (A) were frequently inserted between R and G. These
      results suggest that T lymphocyte expansion may result from the response to
      antigens widely existing in humans, and that the extensive clonal expansion of a
      limited number of T cells leads to contracted CDR3 diversity and post-transplant
      skewed TCR repertoires.

PMID- 11319591
TI  - High frequency of positive surveillance for cytomegalovirus (CMV) by PCR in
      allograft recipients at low risk of CMV.
AB  - Cytomegalovirus (CMV) causes significant morbidity and mortality following
      allogeneic haemopoietic stem cell transplantation. A pre-emptive strategy for
      ganciclovir therapy is widely used, where treatment is commenced on finding
      positive evidence of CMV replication. Surveillance by PCR has increased the
      sensitivity for CMV detection, but it is not known whether this may detect cases
      with evidence of CMV DNAemia who have a low probability of CMV disease. We
      reviewed our experience of CMV infection and disease since introducing CMV
      surveillance by PCR. All 30 allografts received bedside leucodepleted CMV
      negative blood products. Seven of 10 CMV-positive recipients of a CMV-positive
      graft developed CMV DNAemia, with three developing clinical disease requiring
      ganciclovir treatment. In contrast, of 11 low risk patients (CMV-negative
      recipients of CMV-negative grafts), six developed evidence of CMV DNAemia
      although only one had clinical evidence of CMV disease requiring ganciclovir.
      Transfusion records confirmed that four of these had received exclusively CMV
      negative blood products. The aetiology of the CMV DNAemia in these cases is
      unclear. It is suggested that before commencing ganciclovir therapy, confirmatory
      CMV antigenaemia testing is carried out on samples which test positive for CMV
      DNA, unless there is high clinical suspicion of CMV disease.

PMID- 11319592
TI  - Early diagnosis of adenovirus infection and treatment with cidofovir after bone
      marrow transplantation in children.
AB  - Adenovirus infection remains an important cause of mortality after bone marrow
      transplantation (BMT). Currently no efficient antiviral treatment is known. Thus,
      testing new modalities of early diagnosis and treatment is a crucial objective.
      Adenovirus infection is defined by the combination of symptoms and the isolation
      of virus from the source of clinical symptoms. The involvement of two or more
      organs and the presence of virus in blood cultures define disseminated disease.
      Seven children with a median age of 7 years received bone marrow transplantation
      for leukemia. All received an unrelated graft without T cell depletion.
      Adenovirus was sought in blood, urine and biopsy specimens using PCR and culture.
      Analysis of biopsy specimens included systematic immunohistochemistry. Cidofovir
      treatment was initiated as soon as biopsy revealed the histopathological signs of
      adenovirus. Cidofovir was given at 5 mg/kg once weekly for 3 weeks then every 2
      weeks. Six patients had diarrhoea and one patient had cystitis. Adenovirus
      infection and disseminated disease were diagnosed in four cases and three cases,
      respectively. In six cases, serotype A31 was isolated from gastrointestinal
      biopsy and in two cases serotypes B2 and C6 were detected in blood and urine.
      Cidofovir treatment was associated with clinical improvement of diarrhoea,
      cystitis and fever in five patients, in whom the virus became undetectable in
      cultures and PCR analyses despite the persistence of immunodeficiency. The median
      follow-up was 360 days after BMT (240-570). One child died of invasive
      aspergillosis and another of disseminated adenovirus after interruption of
      cidofovir therapy. Further studies in immunocompromised patients will be needed
      to extend these promising results concerning the role of cidofovir in adenovirus
      infection.

PMID- 11319593
TI  - Retrospective multivariate analysis of hepatic veno-occlusive disease after blood
      or marrow transplantation: possible beneficial use of low molecular weight
      heparin.
AB  - This retrospective cohort study of 462 consecutive adult allogeneic and
      autologous blood or marrow transplantation (BMT) patients compared the incidence
      of hepatic veno-occlusive disease (VOD) after BMT with three prophylactic
      regimens. Patients receiving heparin (Hep), heparin + prostaglandin E1 (Hep +
      PGE1) or low molecular weight heparin (LMWH) as a prophylactic VOD regimen were
      compared to a historical cohort receiving no VOD prophylaxis. Of 462 BMT
      patients, VOD was diagnosed in 22% (31 of 142) of the no prophylaxis group, 11%
      (11 of 104) of the Hep, 12% (13 of 110) in the Hep + PGE1 and 4% (four of 106) of
      the LMWH group (P = 0.0002). VOD was the primary cause of death in 20% (12 of
      59). By multivariate logistic regression, independent risk factors for developing
      VOD were: no VOD prophylactic regimen, unrelated allogeneic BMT, Karnofsky
      performance score (KPS) < 80 and aspartate aminotransferase (AST) > or =50 U/l.
      There was no increase in the rate of death due to hemorrhagic events or VOD in
      any prophylaxis group compared to the control group. Prospective randomized
      trials of Hep vs LMWH vs placebo are warranted to assess the efficacy of heparin
      compounds in the prevention of VOD.

PMID- 11319595
TI  - Thrombotic thrombocytopenic purpura-like syndromes following bone marrow
      transplantation: an analysis of associated conditions and clinical outcomes.
AB  - The diagnosis and treatment of thrombotic thrombocytopenic purpura (TTP) in
      patients following BMT are often uncertain and unsuccessful. To better understand
      the evaluation and management of these patients, we describe 17 patients treated
      with plasma exchange for a presumptive diagnosis of TTP following BMT during a 10
      year period, 1989-1998. Because of the uncertainty of the diagnosis, these
      patients are described as having a 'TTP-like syndrome'. All 17 patients had
      received an allogeneic BMT. Comparison with the other 245 patients who had an
      allogeneic BMT during the same period demonstrated that patients with a TTP-like
      syndrome more frequently had unrelated and/or HLA-mismatched donors, and had also
      experienced more serious complications: grade III-IV acute GVHD and systemic
      bacterial, fungal, and viral infections. Three months after the diagnosis of the
      TTP-like syndrome, only four of 17 patients (24%) were alive; currently only one
      patient survives. These data emphasize: (1) the diagnosis of TTP following BMT is
      uncertain because of the presence of multiple BMT-associated complications. (2)
      The outcome of patients with TTP-like syndromes following BMT is poor. (3) Urgent
      intervention with plasma exchange when TTP is suspected following BMT may not
      always be appropriate. Alternative explanations for the signs and symptoms should
      be considered and treated aggressively.

PMID- 11319594
TI  - Serum hyaluronic acid in patients with veno-occlusive disease following bone
      marrow transplantation.
AB  - The development of hepatic veno-occlusive disease following bone marrow
      transplantation is associated with high-dose combination cytoreductive therapy.
      Experimental models have suggested that drug-induced injury to hepatic sinusoidal
      endothelial cells is involved in the pathogenesis of this syndrome. Hyaluronic
      acid is a polysaccharide that is metabolized, almost exclusively, by hepatic
      sinusoidal endothelial cells. The aim of the present study was to evaluate serum
      hyaluronic acid as a marker for endothelial cell injury in patients with veno
      occlusive disease following bone marrow transplantation. Hyaluronic acid was
      measured in sera from patients with and without veno-occlusive disease using an
      enzyme-linked protein binding assay. Mean peak serum hyaluronic acid levels were
      significantly greater in patients who had a diagnosis of VOD compared to those
      transplant patients who did not, 1173.4 +/- 982.9 vs 444.9 +/- 735.6 ng/ml (P =
      0.01). Serial serum samples obtained from a separate cohort of patients also
      demonstrated that serum hyaluronic acid levels were higher in patients with
      moderate or severe veno-occlusive disease compared to those with none or mild
      disease at days 7, 17 and 25 following transplantation (greatest difference at
      day 25: 366 +/- 327 vs 126 +/- 151, P = 0.01). Serum hyaluronic acid levels are
      increased in veno-occlusive disease and increase over time in patients with
      severe disease. Further studies are required to determine if elevated serum
      hyaluronic acid levels are due to decreased clearance by injured hepatic
      sinusoidal endothelial cells or increased production from early hepatic
      fibrogenesis associated with the acute liver injury.

PMID- 11319596
TI  - Dendritic cell-mediated stimulation of the in vitro lymphocyte response to
      Aspergillus.
AB  - Lymphocytes play a major role in host defense against Aspergillus, but little is
      known about the contribution of dendritic cells (DC) to antifungal immunity in
      humans. We have observed that DC derived from normal volunteers phagocytose heat
      killed A. fumigatus conidia. Following 24 h of exposure to the fungus, DC
      displayed an increase in the mean fluorescence intensity of HLA-DR, CD80, and
      CD86, and an increase in the percentage of CD54(+) cells. These DC also displayed
      increased production of IL-12. DC derived from CD34(+) progenitors or monocytes
      stimulated autologous lymphocytes to proliferate and produce high levels of
      interferon-gamma, but not interleukin-10, in response to fungal antigen. DC
      generated from CD34(+) progenitors collected prior to autologous or allogeneic
      stem cell transplantation also partially restored the in vitro antifungal
      proliferative response of lymphocytes obtained from patients 1 month after
      transplantation. These results suggest that DC are important to host-response to
      A. fumigatus, and that ex vivo-generated DC might be useful in restoring or
      enhancing the antifungal immunity after hematopoietic stem cell transplantation.

PMID- 11319597
TI  - Recurrent disseminated retinoblastoma in a 7-year-old girl treated successfully
      by high-dose chemotherapy and CD34-selected autologous peripheral blood stem cell
      transplantation.
AB  - A localized retinoblastoma of the left eye in a 7-year-old girl, was treated by
      enucleation. She received no additional therapy. Four months later, metastases of
      retinoblastoma in the lymph nodes, bone and bone marrow were diagnosed. Relapse
      chemotherapy consisting of three courses of vincristine, cyclophosphamide,
      etoposide and carboplatin led to a second complete remission. Subsequent high
      dose chemotherapy with thiotepa, etoposide and carboplatin and autologous stem
      cell transplantation with CD34-selected stem cells were successful, with no
      adverse effects. No radiotherapy was given and the girl remains in continuous
      second remission with a follow-up of more than 4 years.

PMID- 11319598
TI  - Cardiac death after autologous stem cell transplantation (ASCT) for treatment of
      systemic sclerosis (SSc): no evidence for cyclophosphamide-induced
      cardiomyopathy.
AB  - In patients with systemic sclerosis (SSc) treatment-related mortality after
      autologous stem cell transplantation (ASCT) appears to be increased as compared
      to patients with hematological malignancies. In our phase I/II study on ASCT in
      autoimmune diseases a patient with SSc died on day 2 after ASCT. Here we report
      the results of the autopsy which revealed advanced pulmonary and cardiac fibrosis
      as the most probable cause of death. In spite of detailed technical examination
      before enrollment, the cardiopulmonary function tests did not reflect the
      advanced stage of the disease. We conclude that in selected patients with SSc,
      biopsies should be performed to reduce mortality after ASCT.

PMID- 11319599
TI  - Indolent aspergillus arthritis complicating fludarabine-based non-myeloablative
      stem cell transplantation.
AB  - Fungal arthritis and osteomyelitis are rare and documented mainly in
      immunocompromised or neutropenic patients. Patients receiving therapeutic
      immunosuppression for organ transplants have also reported to suffer from
      aspergillus osteoarthritis. We describe two patients with aspergillus arthritis
      of the knee joint following fludarabine-based non-myeloablative stem cell
      transplantation. Both were suffering from acute and chronic GVHD and treated with
      heavy immunosuppression including steroids and cyclosporine. Interestingly in one
      of our patients, the arthritis was almost asymptomatic and did not spread to
      other organs. Heavy pre- and post-transplant immunosuppression is a major risk
      factor for invasive fungal infection, which can involve remote organs and
      manifest in an indolent and atypical manner.

PMID- 11319600
TI  - Expression of a free gamma heavy chain in serum following autologous stem cell
      transplantation for IgG kappa multiple myeloma.
AB  - A 41-year-old male with IgG kappa multiple myeloma is described. He developed a
      free gamma heavy chain without an accompanying light chain following high-dose
      chemotherapy and autologous peripheral blood stem cell transplantation. The free
      gamma heavy chain was detected in serum and urine specimens 2 months after
      transplant, and eventually evolved into an IgG kappa monoclonal protein with
      electrophoretic properties similar to the original myeloma protein. Although the
      origin of the free gamma heavy chain remains uncertain, it was most likely
      related to the underlying plasma cell malignancy and, therefore, was an early
      sign of disease relapse.

PMID- 11319602
TI  - Insight into age-related macular degeneration: new vision in sight.

PMID- 11319603
TI  - p53-dependent apoptosis induced by proteasome inhibition in mammary epithelial
      cells.
AB  - We have examined the effects of inhibition of the 26S proteasome in a murine
      mammary cell line, KIM-2 cells using the peptide aldehyde inhibitor MG132. These
      studies have demonstrated a clear requirement for proteasome function in cell
      viability. Induction of apoptosis was observed following MG132 treatment in KIM-2
      cells and this death was shown to be dependent on the cell actively traversing
      the cell cycle. KIM-2 cells were generated using a temperature sensitive T
      antigen (Tag) and studies at the permissive temperature (33 degrees C) have shown
      that a Tag binding protein was essential for this apoptotic response. Studies in
      two additional cell lines, HC11, which is a mammary epithelial cell line carrying
      mutant p53 alleles and p53 null ES cells suggest that p53 is actively required
      for the apoptosis induced as a consequence of proteasome inhibition. These
      results suggest a pivotal role for the 26S proteasome degradation pathway in
      progression through the cell cycle in proliferating cells.

PMID- 11319604
TI  - Detection of drug-induced apoptosis and necrosis in human cervical carcinoma
      cells using 1H NMR spectroscopy.
AB  - Apoptosis and necrosis need to be differentiated in order to distinguish drug
      induced cell death from spontaneous cell death due to hypoxia. The ability to
      differentiate between these two modes of cell death, especially at an early stage
      in the process, could have a significant impact on accessing the outcome of
      anticancer drug therapy in the clinic. Nuclear magnetic resonance spectroscopy
      was used to distinguish apoptosis from necrosis in human cervical carcinoma
      (HeLa) cells. Apoptosis was induced by treatment with the topoisomerase II
      inhibitor etoposide, whereas necrosis was induced by the use of ethacrynic acid
      or cytochalasin B. We found that the intensity of the methylene resonance
      increases significantly as early as 6 h after the onset of apoptosis, but that no
      such changes occur during necrosis. The spectral intensity ratio of the methylene
      to methyl resonances also shows a high correlation with the percentage of
      apoptotic cells in the sample (r2=0.965, P<0.003).

PMID- 11319605
TI  - Developmental regulation of the bcl-2 family during spermatogenesis: insights
      into the sterility of bcl-w-/- male mice.
AB  - Expression of bcl-w, a close relative of bcl-2 is essential for male fertility in
      mice. Although the initial wave of spermatogenesis in bcl-w -/- mice proceeds
      normally until 3-4 weeks of age, adults fail to produce sperm. To clarify why bcl
      w is essential for adult but not juvenile spermatogenesis, we investigated the
      expression pattern of eight bcl-2 family members. We found that both the level
      and pattern of expression varied in different cell types during juvenile and
      adult spermatogenesis. Anti-apoptotic genes bcl-w, bcl-2 and bcl-xL were all
      expressed in spermatogonia during juvenile spermatogenesis, but only bcl-w was
      detected in spermatogonia of adult mice. A similar shift was evident in Sertoli
      cells. This developmental regulation may co-ordinate physiological germ cell
      apoptosis in wild type mice and account for the time of onset for pathological
      germ cell apoptosis in bcl-w -/- animals.

PMID- 11319606
TI  - Staurosporine-induced apoptosis of HPV positive and negative human cervical
      cancer cells from different points in the cell cycle.
AB  - In the present study, we compare the sensitivity of CaSki and HeLa cells (HPV
      positive, wild-type p53) and C33A cells (HPV negative, mutated p53) to a protein
      kinase inhibitor, the staurosporine (ST). We show that ST can reversibly arrest
      the three cervical-derived cell lines, either in G1 or in G2/M. Beyond certain ST
      concentrations or/and over 24 h exposure, the cells underwent apoptosis. This
      process took place in G1 and G2/M for C33A and CaSki plus HeLa cell lines,
      respectively. By using an in vitro cell-free system, we demonstrated that
      cytoplasmic extracts from apoptotic cells were sufficient to induce hallmarks of
      programmed cell death on isolated nuclei. Moreover, we found that only G2/M
      cytoplasmic extracts from viable CaSki and HeLa cells supplemented with ST,
      triggered apoptosis while exclusively G1 cytoplasmic fractions from C33A cells
      were efficient. Our study describes a possible involvement of the HPV infection
      or/and p53 status in this different ST-induced apoptosis susceptibility.

PMID- 11319607
TI  - Elevated DNA double strand breaks and apoptosis in the CNS of scid mutant mice.
AB  - Genetic approaches have provided evidence that DNA end-joining problems serve an
      essential role in neuronal survival during development of mammalian embryos. In
      the present study, we tested whether the DNA repair enzyme, DNA dependent protein
      kinase, plays an important role in the survival of cerebral cortical neurons in
      mice. DNA-PK is comprised of a DNA-binding subunit called Ku and a catalytic
      subunit called DNA-PKcs. In mice with the scid mutation, DNA-PKcs is truncated
      near the kinase domain, which causes loss of kinase activity. We compared the
      spatial and temporal aspects of neuronal cell death in scid versus isogenic wild
      type embryos and found a significant increase in dying cells in scid mice, as
      assessed by nuclear changes, DNA fragmentation and caspase-3 activity. Additional
      biochemical and immunocytochemical studies indicated that of several DNA repair
      enzymes investigated, only PARP was increased in scid mice, possibly in response
      to elevated DNA strand breaks.

PMID- 11319608
TI  - Pro-caspase-3 overexpression sensitises ovarian cancer cells to proteasome
      inhibitors.
AB  - The ubiquitin-proteasome pathway plays a critical role in the degradation of
      several proteins involved in the cell cycle. Dysregulation of this pathway leads
      to inhibition of cellular proliferation and the induction of apoptosis.
      Ubiquitination and its downstream consequences have been investigated intensively
      as targets for the development of drugs for tumour therapy. Here we have
      investigated the mechanism of apoptosis induced by the proteasome inhibitors MG
      132, lactacystin and calpain inhibitor I (ALLN), in the HEK 293 cell line and the
      ovarian cancer cell lines SKOV3 and OVCAR3. We have found strong caspase-3-like
      and caspase-6-like activation upon treatment of HEK 293 cells with MG-132. Using
      a tricistronic expression vector based on a tetracycline-responsive system we
      generated stable SKOV3 nd OVCAR3 cell lines with inducible expression of pro
      caspase-3. Induction of pro-caspase-3 expression in normally growing cells does
      not induce apoptosis. However, in the presence of the proteasome inhibitors MG
      132, lactacystin or ALLN we found that cells overexpressing pro-caspase-3 are
      rapidly targeted for apoptosis. Our results demonstrate that pro-caspase-3 can
      sensitise ovarian cancer cells to proteasome inhibitor-induced apoptosis, and a
      combination of these approaches might be exploited for therapy of ovarian and
      other cancers.

PMID- 11319609
TI  - A20 zinc finger protein inhibits TNF-induced apoptosis and stress response early
      in the signaling cascades and independently of binding to TRAF2 or 14-3-3
      proteins.
AB  - A20 zinc finger protein is a negative regulator of tumor necrosis factor (TNF)
      induced signaling pathways leading to apoptosis, stress response and
      inflammation. A20 has been shown to bind to TNF-receptor-associated factor 2
      (TRAF2) and 14-3-3 chaperone proteins. Our data indicate that the zinc finger
      domain of A20 is sufficient and that neither TRAF2 nor 14-3-3 binding is
      necessary for the inhibitory effects of A20. Mutations in the 14-3-3 binding site
      of A20 did, however, result in a partial cleavage of A20 protein suggesting that
      14-3-3 chaperone proteins may stabilize A20. Furthermore, we show that A20 acts
      early in TNF-induced signaling cascades blocking both TNF-induced rapid
      activation of c-Jun N-terminal kinase and processing of the receptor-associated
      caspase-8. Taken together our data indicate that the zinc finger domain of A20
      contains all necessary functional domains required for the inhibition of TNF
      signaling and that A20 may function at the level of the receptor signaling
      complex.

PMID- 11319610
TI  - CD95 ligand (CD95L) immunohistochemistry: a critical study on 12 antibodies.
AB  - In recent years, some studies on the expression of CD95(Fas/APO-1) ligand (CD95L)
      in tissues or cells raised concerns about the specificity of the antibodies used.
      We therefore tested 12 CD95L antibodies for their reliability in
      immunocyto/histochemistry by (i) staining CD95L-transfected and control CV-1/EBNA
      cells and (ii) comparing staining patterns in immunohistochemically labeled
      tissue sections with the localization of CD95L+ cells in in situ hybridization.
      While G247-4, NOK-1, NOK-2, 4H9, and MIKE-1 stained CD95L-transfected cells and
      did not significantly bind to controls, G247-4 was the only antibody giving
      satisfying signals in tissue sections perfectly matching the distribution of
      CD95L+ cells by in situ hybridization. MAb 33, C-20, and N-20 comparably stained
      both transfected and control cells and showed considerable background or falsely
      positive staining in sections. MIKE-2, 8B8, A11, and 4A5 did not or only very
      faintly bind to either cells and, thus, were not tested on sections. We conclude
      that G247-4 is the only tested antibody that is recommendable for
      immunohistochemistry.

PMID- 11319611
TI  - Dexamethasone inhibits spontaneous apoptosis in primary cultures of human and rat
      hepatocytes via Bcl-2 and Bcl-xL induction.
AB  - We examined the effects of dexamethasone (DEX) on the apoptotic process in
      primary cultures of human and rat hepatocytes. DEX prolonged cell viability,
      inhibited the development of an apoptotic morphology, and stabilised the
      expression of procaspase-3 in both human and rat hepatocytes. In addition, the
      inhibition of apoptosis by DEX was strongly correlated with a decrease of caspase
      3-like protease activity. Moreover, DEX treatment increased the expression of
      anti-apoptotic Bcl-2 and Bcl-xL proteins in human and rat hepatocytes,
      respectively, whereas the expression of pro-apoptotic proteins Bcl-xS or Bad was
      not detected or remained unchanged. The bcl-xL transcript is regulated at the
      transcriptional level and its expression paralleled that of Bcl-xL protein in DEX
      treated rat hepatocytes. Taken together, these results indicate that this
      glucocorticoid exerts a protective role on cell survival and it delays apoptosis
      of human and rat hepatocytes by modulating caspase-3-like protease activity and
      bcl-2 and bcl-x gene expression.

PMID- 11319612
TI  - Lysosomal enzymes in the macronucleus of Tetrahymena during its apoptosis-like
      degradation.
AB  - A key characteristic of apoptosis is its regulated nuclear degradation. Apoptosis
      like nuclear degradation also occurs in the ciliated unicellular organism,
      Tetrahymena thermophila. Chromatin of the macronucleus undergoes massive
      condensation, a process that can be blocked by caspase inhibitors. The nucleus
      becomes TUNEL-positive, and its DNA is cleaved into nucleosome-sized fragments.
      In a matter of hours the macronucleus is completely degraded, and disappears. The
      condensed nucleus sequesters acridine orange, which means that it might become an
      acidic compartment. We therefore asked whether lysosomal bodies fuse with the
      condensed macronucleus to form an autophagosome. We monitored acid phosphatase
      (AP) activity, which is associated with lysosomal bodies but is not found in
      normal nuclei. We find that after the macronucleus condenses AP activity is
      localized in cap-like structures at its cortex. Later, after the degrading
      macronucleus loses much of its DNA, acid phosphatase deposits appear deeper
      within the nucleus. We conclude that although macronuclear elimination is
      initiated by an apoptosis-like mechanism, its final degradation may be achieved
      through autophagosomy.

PMID- 11319613
TI  - Apoptosis-inducing protein, AIP, from parasite-infected fish induces apoptosis in
      mammalian cells by two different molecular mechanisms.
AB  - AIP (apoptosis-inducing protein) is a protein purified and cloned from Chub
      mackerel infected with the larval nematode, Anisakis simplex, which induces
      apoptosis in various mammalian cells including human tumor cell lines. AIP has
      shown structural and functional homology to L-amino acid oxidase (LAO) which
      oxidizes several L-amino acids including L-lysine and AIP-induced apoptosis has
      been suggested to be mediated by H2O2 generated by LAO activity of AIP. In this
      study, we confirmed that recombinant AIP generated enough H2O2 in culture medium
      to induce rapid apoptosis in cells and this apoptosis was clearly inhibited by co
      cultivation with antioxidants such as catalase and N-acetyl-cysteine.
      Surprisingly, however, we found that AIP still could induce H2O2-independent
      apoptosis more slowly than H2O2-dependent one in HL-60 cells even in the presence
      of antioxidants. In addition, the HL-60-derived cell line HP100-1, which is a
      H2O2-resistant variant, underwent apoptosis on treatment with AIP with a similar
      delayed time course. The latter apoptosis was completely blocked by addition of L
      lysine to the culture medium, which is the best substrate of AIP as LAO,
      indicating that decreased concentration of L-lysine in the culture medium by AIP
      treatment induced apoptosis. We also showed that the both apoptosis by AIP were
      associated with the release of cytochrome c from mitochondria and activation of
      caspase-9, and overexpressed Bcl-2 could inhibit both of the AIP-induced
      apoptosis. These results indicate that AIP induces apoptosis in cells by two
      distinct mechanisms; one rapid and mediated by H2O2, the other delayed and
      mediated by deprivation of L-lysine, both of which utilize caspase-9/cytochrome c
      system.

PMID- 11319614
TI  - Apoptosis-induced cleavage of keratin 15 and keratin 17 in a human breast
      epithelial cell line.
AB  - Keratin 15 (K15) and keratin 17 (K17) are intermediate filament (IF) type I
      proteins that are responsible for the mechanical integrity of epithelial cells.
      By analyzing the human breast epithelial cell line H184A1 before and after
      induction of apoptosis by high-resolution two-dimensional gel electrophoresis (2
      DE) we identified the caspase-mediated cleavage of keratins 15 and 17. After
      induction of apoptosis three fragments of both K15 and K17 could be observed by 2
      -DE. K15 and K17 proteolysis was observed during staurosporine-induced apoptosis
      and anoikis (anchorage-dependent apoptosis) as well and was shown to be caspase
      dependent. By using mass spectrometry we could determine the caspase cleavage
      sites, one in K15 and two in K17. The sequence VEMD/A at the cleavage site
      located in the conserved linker region was found in K15 and K17. A further
      cleavage site was identified in the tail region of K17 with the recognition motif
      EVQD/G.

PMID- 11319615
TI  - The checkpoint monitoring chromosomal pairing in male meiotic cells is p53
      independent.

PMID- 11319616
TI  - Administration of subtumor regression dosage of TNF-alpha to mice with pre
      existing parental tumors augments the vaccination effect of TNF gene-modified
      tumor through the induction of MHC class I molecule.
AB  - One obstacle in treating pre-existing parental tumors by vaccination with
      cytokine gene-modified tumor cells is the impaired expression of immune-related
      molecules such as MHC class I. In this study, to enhance MHC class I expression
      on pre-inoculated parental tumors, low dose TNF (300 U, 500 U, 1000 U), that is,
      TNF at levels shown to cause neither tumor regression nor any severe adverse
      reaction, was systemically injected into parental tumors bearing mice before
      vaccination with TNF gene-modified Meth-A cells or B-16 cells. Since the class I
      expression was confirmed to continue for at least 24 h following administration
      of TNF, TNF was administered 6 h before vaccination. Complete regression of
      relatively large parental tumors (M0) (8.0-10.0 mm in diameter) was observed in
      five of eight mice treated with 1000 U TNF, partial regression was observed in
      mice treated with 500 U, and a lesser yet significant regression was observed in
      mice treated with only 300 U. Contrarily, in the mice which had received
      vaccination without the TNF pretreatment, no complete regression was observed.
      This effect was inhibited with the anti-class I antibody or anti-CD8 antibody.
      Growth of a re-established, B16 tumor was significantly suppressed with a
      combination of TNF preadministration and vaccination of TNF gene-modified B16.
      These results indicate that pre-administration of low-dose TNF may be promising
      for enhancing vaccination effects of TNF gene-modified tumor cells.

PMID- 11319617
TI  - Polyethylenimine-mediated gene transfer into pancreatic tumor dissemination in
      the murine peritoneal cavity.
AB  - Although peritoneal dissemination of cancer cells often occurs at the advanced
      stages of pancreatic, gastric or ovarian cancers, no effective therapy has been
      established. Cationic lipid-mediated gene transfer into peritoneal dissemination
      may offer a prospect of safe therapies, but vector improvements are needed with
      regard to the efficiency and specificity of the gene transfer. In this study, the
      intraperitoneal injection of plasmid DNA:polyethylenimine (PEI) complexes into
      mice was evaluated as a gene delivery system for the peritoneal disseminations.
      The luciferase and beta-galactosidase genes were used as marker genes. PEI was
      more efficient than the cationic lipids examined in this study in vivo, and the
      transgene was preferentially expressed in the tumors. Although PCR analysis
      showed that the injected DNA was delivered to various organs, the distributed DNA
      became undetectable by 6 months after the gene transfer. Blood chemistry and
      histological analysis showed no significant toxicity in the injected mice. This
      study demonstrated that the intraperitoneal injection of DNA:PEI is a promising
      delivery method to transduce a gene into disseminated cancer nodules in the
      peritoneal cavity.

PMID- 11319618
TI  - DNA binding chelates for nonviral gene delivery imaging.
AB  - Noninvasive in vivo monitoring of gene delivery would provide a critically
      important information regarding the spatial distribution, local concentration,
      kinetics of removal and/or biodegradation of the expression vector. We developed
      a novel approach to noninvasive gene delivery imaging using heterobifunctional
      peptide-based chelates (PBC) bearing double-stranded DNA-binding groups and a
      technetium-binding amino acid motif. One of such chelates: Gly-Cys(Acm)-Gly
      Cys(Acm)-Gly-Lys(4)-Lys-(N-epsilon-[4-(psoralen-8-yloxy)]butyrate)-NH(2) has been
      characterized and labeled with reduced (99m)Tc pertechnetate (oxotechnetate). The
      psoralen moiety (a DNA binding group of PBC) allowed linking to double-stranded
      DNA upon short-term irradiation with the near UV range light (>320 nm).
      Approximately 30-40% of added (99m)Tc-labeled PBC was nonextractable and co
      eluted with a model pCMV-GFP vector during the gel-permeation chromatography.
      Nuclear imaging of "naked" DNA and DNA complexes with lipid-based transfection
      reagents ("lipoplexes") has been performed after systemic or local administration
      of (99m)Tc-PBC-labeled DNA in mice. Imaging results were corroborated with the
      biodistribution using (99m)Tc-PBC and (32)P-labeled DNA and lipoplexes. A
      markedly different biodistribution of (99m)Tc PBC-labeled DNA and lipoplexes was
      observed with the latter being rapidly trapped in the liver, spleen and lung.
      (99m)Tc PBC-DNA was used as an imaging tracer during in vivo transfection of B16
      melanoma by local injection of "naked" (99m)Tc PBC-DNA and corresponding
      lipoplexes. As demonstrated by nuclear imaging, (99m)Tc PBC-DNA lipoplexes showed
      a slower elimination from the site of injection than (99m)Tc PBC-DNA alone. This
      result correlated with a higher expression of marker mRNA and green fluorescent
      protein as determined using RT-PCR and immunohistochemistry, respectively.

PMID- 11319619
TI  - Delivery of FGF-2 but not VEGF by encapsulated genetically engineered myoblasts
      improves survival and vascularization in a model of acute skin flap ischemia.
AB  - Stimulating angiogenesis by gene transfer approaches offers the hope of treating
      tissue ischemia which is untreatable by currently practiced techniques of vessel
      grafting and bypass surgery. Vascular endothelial growth factor (VEGF) and basic
      fibroblast growth factor (FGF-2) are potent angiogenic molecules, making them
      ideal candidates for novel gene transfer protocols designed to promote new blood
      vessel growth. In this study, an ex vivo gene therapy approach utilizing cell
      encapsulation was employed to deliver VEGF and FGF-2 in a continuous and
      localized manner. C(2)C(12) myoblasts were genetically engineered to secrete
      VEGF(121), VEGF(165) and FGF-2. These cell lines were encapsulated in hollow
      microporous polymer membranes for transplantation in vivo. Therapeutic efficacy
      was evaluated in a model of acute skin flap ischemia. Capsules were positioned
      under the distal, ischemic region of the flap. Control flaps showed 50% necrosis
      at 1 week. Capsules releasing either form of VEGF had no effect on flap survival,
      but induced a modest increase in distal vascular supply. Delivery of FGF-2
      significantly improved flap survival, reducing necrosis to 34.2% (P < 0.001).
      Flap vascularization was significantly increased by FGF-2 (P < 0.01), with
      numerous vessels, many of which had a large lumen diameter, growing in the
      proximity of the implanted capsules. These results demonstrate that FGF-2,
      delivered from encapsulated cells, is more efficacious than either VEGF(121) or
      VEGF(165) in treating acute skin ischemia and improving skin flap survival.
      Furthermore, these data attest to the applicability of cell encapsulation for the
      delivery of angiogenic factors for the treatment and prevention of tissue
      ischemia.

PMID- 11319620
TI  - In vivo suppression of restenosis in balloon-injured rat carotid artery by
      adenovirus-mediated gene transfer of the cell surface-directed plasmin inhibitor
      ATF.BPTI.
AB  - Injury-induced neointimal development results from migration and proliferation of
      vascular smooth muscle cells (SMC). Cell migration requires controlled
      proteolytic degradation of extracellular matrix surrounding the cell. Plasmin is
      a major contributor to this process by degrading various matrix proteins
      directly, or indirectly by activating matrix metalloproteinases. This makes it an
      attractive target for inhibition by gene transfer. An adenoviral vector,
      Ad.ATF.BPTI, was constructed encoding a hybrid protein, which consists of the
      aminoterminal fragment (ATF) of urokinase-type plasminogen activator (u-PA)
      linked to bovine pancreas trypsin inhibitor (BPTI), a potent inhibitor of
      plasmin. This hybrid protein binds to the u-PA receptor, thereby inhibiting
      plasmin activity at the cell surface, and was found to be a potent inhibitor of
      cell migration in vitro. Local infection with Ad.ATF.BPTI of balloon-injured rat
      carotid artery resulted in detectable expression of ATF.BPTI mRNA and protein in
      the vessel wall. Morphometric analysis of arterial cross-sections revealed that
      delivery of Ad.ATF.BPTI to the carotid artery wall at the time of balloon injury
      inhibited neointima formation by 53% (P < 0.01) at 14 days and 19% (P = NS) at 28
      days after injury when compared with control vector-infected arteries.
      Intima/media ratios were decreased by 60% (P < 0.01) and 35% (P < 0.05) at 14 and
      28 days, respectively, when compared with control vector-infected arteries.
      Furthermore, a small but significant increase in medial area was found in the
      Ad.ATF.BPTI-treated arteries at 28 days (P < 0.05). These results show that local
      infection of the vessel wall with Ad.ATF.BPTI reduces neointima formation,
      presumably by inhibiting SMC migration, thereby offering a novel therapeutic
      approach to inhibiting neointima development.

PMID- 11319621
TI  - Intratumoral IL-18 gene transfer improves therapeutic efficacy of antibody
      targeted superantigen in established murine melanoma.
AB  - Antibody-targeted superantigen C215Fab-SEA is a fusion protein of staphylococcal
      enterotoxin A (SEA) and the Fab region of the tumor-reactive C215 mAb. It can
      trigger CTL against C215 antigen-positive tumor cells and induce tumor
      suppressive cytokines. However, the antitumor effect of C215Fab-SEA is not
      satisfactory because of suboptimal production of Th1 cytokines after repeated
      administration. Interleukin 18 (IL-18) is a novel cytokine with profound effects
      on Th1 cellular response. In this study, we showed that adenovirus-mediated
      intratumoral IL-18 gene transfer strongly improved the therapeutic efficacy of
      C215Fab-SEA in the pre-established C215 antigen-expressing B16 melanoma murine
      model. More significant tumor inhibition and prolonged survival time were
      observed in tumor-bearing mice received combined therapy of C215Fab-SEA and Ad IL
      18 than those of mice treated with C215Fab-SEA or AdIL-18 alone. Combination
      therapy augmented NK and CTL activities of tumor-bearing mice more markedly. The
      production of IL-2 and IFN-gamma also increased more significantly. More potent
      antitumor effect of combined therapy was observed in IL-10 KO mice with enhanced
      Th1 response. Our data demonstrated that the antitumor effect of C215Fab-SEA
      immunotherapy could be potentiated significantly by combination with intratumoral
      IL-18 gene transfer through more efficient activation of Th1 immune responses.

PMID- 11319622
TI  - Antinociceptive effect of a genomic herpes simplex virus-based vector expressing
      human proenkephalin in rat dorsal root ganglion.
AB  - Endogenous opiate peptides acting pre- and post-synaptically in the dorsal horn
      of spinal cord inhibit transmission of nociceptive stimuli. We transfected
      neurons of the dorsal root ganglion in vivo by footpad inoculation with 30 microl
      (3 x 10(7) p.f.u.) of a replication-incompetent (ICP4-deleted) herpes simplex
      virus (HSV) vector with a cassette containing a portion of the human
      proenkephalin gene coding for 5 met- and 1 leu-enkephalin molecules under the
      control of the human cytomegalovirus immediate-early promoter (HCMV IEp) inserted
      in the HSV thymidine kinase (tk) locus. Vector-directed expression of enkephalin
      produced a significant antinociceptive effect measured by the formalin footpad
      test, that was most prominent in the delayed ("tonic") phase 20-70 min after the
      administration of formalin. The magnitude of the antinociceptive effect
      diminished over 4 weeks after transduction, but reinoculation of the vector
      reestablished the analgesic effect, without evidence for the development of
      tolerance. The antinociceptive effect was blocked completely by intrathecal
      naltrexone. These results suggest that gene therapy with an enkephalin-producing
      herpes-based vector may prove useful in the treatment of pain.

PMID- 11319623
TI  - Genetic prodrug activation therapy (GPAT) in two rat prostate models generates an
      immune bystander effect and can be monitored by magnetic resonance techniques.
AB  - Treatment of hormone refractory prostate cancer requires new treatment
      strategies. Genetic prodrug activation therapy (GPAT) may provide a new
      therapeutic avenue. In this study the antitumour efficacy of the gene encoding
      herpes simplex virus thymidine kinase (HSVtk) activating the prodrug ganciclovir
      (GCV) was compared in two models of ectopic (subcutaneous) rat prostate cancer.
      Both models, which differ in their characteristics, were previously shown to be
      weakly immunogenic but susceptible to immunotherapy. Tumour cell lines were
      stably transfected with HSVtk and were rendered highly sensitive to GCV. Little
      or no bystander killing effect was observed by tk-transfected cells on wild-type
      cells in vitro. However, a significant in vivo bystander effect was observed
      suggesting an immune-mediated response. Indeed, such an immune response was
      capable of slowing the growth of distant wild-type tumours and increased overall
      animal survival. A T helper 1 immune response was generated as a result of GCV
      activation and cell kill, demonstrated by the secretion of IFNgamma by cultured
      splenocytes in response to tumour cells. BrDU staining of tk-transfected cells
      treated with GCV in vitro suggested apoptotic cell death, but Annexin V staining
      was less marked for one of the cell lines. Serial in vivo monitoring by non
      invasive magnetic resonance spectroscopy (MRS) of the tk-transfected MATLyLu
      tumours demonstrated a decreased ATP/Pi ratio (a measure of cell energy status)
      during growth and an increase in the ATP/Pi ratio during regression initiated by
      treatment with GCV. Further, significant differences were found in the
      phosphomonester (PME) to total phosphate (SigmaP) ratios in treated compared with
      untreated tumours, a result rarely seen in animal models, but commonly observed
      in patients. This study showed that a Th1-biased immune response generated by
      killing prostate tumour cells with tk/GCV can kill distant as well as local wild
      type tumour cells. These findings suggest that GPAT may have a potential
      application in patients with both confined and metastatic prostate cancer and MRS
      may provide a method of monitoring response to treatment.

PMID- 11319624
TI  - The telomerase reverse transcriptase promoter drives efficacious tumor suicide
      gene therapy while preventing hepatotoxicity encountered with constitutive
      promoters.
AB  - In human cells, telomerase activity is regulated by transcriptional control of
      the telomerase reverse transcriptase gene (hTERT) whose product is the catalytic
      subunit of the enzyme. The hTERT promoter is active in virtually all types of
      tumors and immortal cells, but is silent in most adult somatic tissues. In this
      study, we placed the herpes simplex virus thymidine kinase gene under the control
      of the hTERT promoter with the aim of restricting its expression to tumor cells.
      In transfection experiments, the hTERT promoter driven thymidine kinase gene
      (hTERTp/TK) conferred ganciclovir sensitivity to all tumor and immortal cell
      lines tested, whereas normal somatic cells remained largely unaffected. Human
      hTERTp/TK-positive cancer cells implanted in nude mice developed into tumors that
      could be eradicated by ganciclovir treatment. The hTERTp/TK cassette was inserted
      into an adenovirus vector and its efficacy in reducing tumor growth was compared
      with that of an adenovirus carrying the thymidine kinase gene under the control
      of the cytomegalovirus immediate-early promoter (CMVp/TK). In a xenograft model
      using the human 143B osteosarcoma cell line, a single injection of either virus
      resulted in equivalent tumor regression and survival upon ganciclovir treatment.
      In animals injected intratumorally with the CMVp/TK adenovirus, expression of the
      thymidine kinase gene was detected in tumors, as well as in liver samples.
      Expression of the suicide gene in combination with ganciclovir resulted in severe
      liver histopathology and in an elevation of hepatic enzymes. In sharp contrast,
      when the hTERT promoter controlled the thymidine kinase gene, transgene
      expression was observed in tumors, but not in liver samples. Normal liver
      function in these animals was confirmed by serum levels of hepatic enzymes that
      were indistinguishable from those of control healthy mice. These results indicate
      that by restricting thymidine kinase expression to tumor cells, the hTERT
      promoter allows the tumoricidal effect of the suicidal gene to be exerted without
      detrimental consequences on healthy tissues and vital organs. The tight
      specificity of expression imparted by the hTERT promoter will assist the
      development of novel approaches to the treatment of a broad array of cancer
      types.

PMID- 11319625
TI  - Physical activity and dietary fiber determine population body fat levels: the
      Seven Countries Study.
AB  - BACKGROUND: A global epidemic of obesity is developing. Current prevalence rates
      are about 20-25% in American adults and 15-20% in Europeans. OBJECTIVE: We
      investigated the association between population levels of physical activity,
      dietary fat, dietary fiber and indicators of body fat. DESIGN: Cross-cultural
      study of 16 cohorts of, in total, 12 763 middle-aged men in seven countries.
      These men were examined between 1958 and 1964. MEASUREMENTS: Height, weight and
      subscapular skinfold thickness were measured. Information about job-related
      physical activity and diet was gathered by questionnaire. RESULTS: The population
      average body mass index (weight/height) varied between 21.8 and 26.0 kg/m2 and
      the population average subscapular skinfold thickness between 8.4 and 23.7 mm.
      The population average physical activity index and dietary fiber intake were both
      strongly inversely related to population average subscapular skinfold thickness
      and explained together 90% of the variance in subscapular skinfold thickness.
      Similar but less strong results were obtained for average population body mass
      index. CONCLUSION: At the population level job-related physical activity and
      dietary fiber but not dietary fat, are important determinants of subscapular
      skinfold thickness.

PMID- 11319626
TI  - The effect of addition of modified guar gum to a low-energy semisolid meal on
      appetite and body weight loss.
AB  - OBJECTIVE: To investigate the effect of addition of modified guar gum (GG) to a
      low-energy semisolid meal on appetite and body weight (BW) loss. SUBJECTS: Twenty
      eight mainly overweight male volunteers (age, 19-56 y; body mass index, 29+/-2 kg
      x m(-2); BW, 89.4+/-9.2 kg). DESIGN: Baseline of one week with self-selected
      diet. Three treatments of 2 weeks with a low-energy diet divided over three times
      a day, consisting of a semisolid meal with (SSM+) or without GG (SSM) or a solid
      meal (SM) with the same energy content (947 kJ) and macronutrient composition,
      and a dinner of the subject's own choice. Washout periods lasted 4 weeks.
      RESULTS: Compared to baseline values, reduction in energy intake and BW loss were
      similar for SSM+, SSM and SM. Appetite (hunger, desire to eat or estimation of
      how much one could eat) was increased in SSM and in SM compared to baseline, but
      not in SSM+. Satiety and fullness in SSM+, SSM and SM were similar to baseline.
      Any intervention was more effective on BW loss when it took place the first time
      compared to the second and third times (2.6+/-0.2 kg, 1.7+/-0.2 kg and 1.1+/-0.2
      kg, respectively; P<0.001). The SM-SSM+-SSM sequence was more effective on BW
      loss compared to the SSM+-SSM-SM sequence (5.6+/-1.0 and 2.5+/-0.6 kg,
      respectively; P<0.05). CONCLUSION: All the three treatments were equally
      effective with respect to BW loss. GG addition to a semisolid meal prevented an
      increase in appetite, hunger and desire to eat, which increase was present in the
      other treatments. However, differences between treatments were not statistically
      significant. The order effect shows that repeated 2-week bouts of dieting become
      increasingly ineffective. The sequence SM-SSM+-SSM was more effective than the
      sequence SSM+-SSM-SM, probably because compliance was relatively higher with the
      SSM+ or SSM diet, and compliance decreased towards the end of the complete
      experiment.

PMID- 11319627
TI  - An herbal supplement containing Ma Huang-Guarana for weight loss: a randomized,
      double-blind trial.
AB  - OBJECTIVE: To examine in overweight humans the short-term safety and efficacy for
      weight loss of an herbal supplement containing Ma Huang, Guarana and other
      ingredients. DESIGN: An 8 week randomized, double-blind placebo controlled study
      of a herbal dietary supplement (72 mg/day ephedrine alkaloids and 240 mg/day
      caffeine). SUBJECTS: Overweight men and women (body mass index, > or =29 and < or
      =35 kg/m2). MEASUREMENTS: The primary outcome variable was body weight change.
      Secondary variables included anthropometric, metabolic and cardiovascular
      changes. RESULTS: Sixty-seven subjects were randomized to either placebo (n=32)
      or active Ma Huang/Guarana (n=35). Twenty-four subjects in each group completed
      the study. Active treatment produced significantly (P<0.006) greater loss of
      weight (X+/-s.d.,-4.0+/-3.4 kg) and fat (-2.1+/-3.0% fat) over the 8-week
      treatment period than did placebo (-0.8+/-2.4 kg and 0.2+/-2.3% fat). Active
      treatment also produced greater reductions in hip circumference and serum
      triglyceride levels. Eight of the 35 actively treated subjects (23%) and none of
      the 32 placebo-treated control subjects withdrew from the protocol because of
      potential treatment-related effects. Dry mouth, insomnia and headache were the
      adverse symptoms reported most frequently by the herbal vs placebo group at the
      final evaluation visit. CONCLUSIONS: This herbal mixture of Ma Huang and Guarana
      effectively promoted short-term weight and fat loss. Safety with long-term use
      requires further investigation.

PMID- 11319628
TI  - Weight-loss maintenance in overweight individuals one to five years following
      successful completion of a commercial weight loss program.
AB  - OBJECTIVE: To determine weight loss maintenance among participants in a
      commercial weight loss program (Weight Watchers) who had reached their goal
      weights 1-5 y previously. DESIGN: A national sample (n=1002) was surveyed by
      phone to obtain demographic and weight-related information. An oversample (n=258)
      was recruited and weighed in person to develop a correction factor for self
      reported weights in the national sample. RESULTS: Based on corrected weights,
      weight regain from 1 to 5 y following weight loss ranged between 31.5 and 76.5%.
      At 5 y, 19.4% were within 5 lb of goal weight, 42.6% maintained a loss of 5% or
      more, 18.8% maintained a loss of 10% or more, and 70.3% were below initial
      weight. CONCLUSIONS: These results are not directly comparable to those obtained
      in clinical settings because of differences in the populations studied.
      Nonetheless, they suggest that the long-term prognosis for weight maintenance
      among individuals who reach goal weight in at least one commercial program is
      better than that suggested by existing research.

PMID- 11319629
TI  - Impact of high-intensity exercise on energy expenditure, lipid oxidation and body
      fatness.
AB  - OBJECTIVE: Two studies were conducted to assess the potential of an increase in
      exercise intensity to alter energy and lipid metabolism and body fatness under
      conditions mimicking real life. METHODS: Study 1 was based on the comparison of
      adiposity markers obtained in 352 male healthy adults who participated in the
      Quebec Family Study who either regularly participated in high-intensity physical
      activities or did not. Study 2 was designed to determine the effects of high
      intensity exercise on post-exercise post-prandial energy and lipid metabolism as
      well as the contribution of beta-adrenergic stimulation to such differences under
      a real-life setting. RESULTS: Results from Study 1 showed that men who regularly
      take part in intense physical activities display lower fat percentage and
      subcutaneous adiposity than men who never perform such activities, and this was
      true even if the latter group reported a lower energy intake (917 kJ/day,
      P<0.05). In Study 2, the high-intensity exercise stimulus produced a greater post
      exercise post-prandial oxygen consumption as well as fat oxidation than the
      resting session, an effect which disappeared with the addition of propranolol. In
      addition, the increase in post-prandial oxygen consumption observed after the
      high-intensity exercise session was also significantly greater than that promoted
      by the low-intensity exercise session. CONCLUSION: These results suggest that
      high-intensity exercise favors a lesser body fat deposition which might be
      related to an increase in post-exercise energy metabolism that is mediated by
      beta-adrenergic stimulation.

PMID- 11319630
TI  - Psychological and behavioral predictors of weight loss during drug treatment for
      obesity.
AB  - OBJECTIVE: This study investigated whether baseline eating behavior, emotions,
      and body image were significant predictors of change in body mass index (BMI)
      over 6 month and 12 month time intervals for individuals enrolled in a weight
      loss program that combined appetite suppressant medications and behavior therapy
      for obesity. METHOD: Participants were asked to complete self-report
      questionnaires at baseline, 6 months, and 12 months. In addition, their height
      and weight were measured and they were administered a body image assessment
      procedure at each time interval. RESULTS: At baseline, perceived hunger, dietary
      restraint, current body size, and trait anxiety were important components in a
      model for prediction of weight loss at 6 months. Perceived hunger, dietary
      restraint, and current body size as measured at baseline were important
      components in the prediction of weight loss at 12 months. These predictive
      variables, together with gender and initial BMI, accounted for 48.6% of the
      variance in weight loss at 6 months and 51.7% of the variance in weight loss at
      12 months. DISCUSSION: These findings suggest that scores on certain paper and
      pencil tests may be useful as predictors of success or failure for individuals
      entering a weight loss program using pharmacological and behavioral
      interventions.

PMID- 11319631
TI  - Plasma leptin concentrations and four-year weight gain among US men.
AB  - OBJECTIVE: Leptin, a primarily adipose tissue-derived protein product of the
      obesity (ob) gene, is an important regulator of energy metabolism. The strong
      association between body fat mass and elevated circulating leptin levels in
      humans suggests that leptin resistance, rather than leptin production, may
      contribute to the development of obesity and associated disorders. The purpose of
      this study is to evaluate the relationship between circulating plasma leptin
      levels and regulation of body weight over time among US men. DESIGN: Four-year
      prospective study. SUBJECTS: A total of 247 men from the Health Professionals
      Follow-up Study, who at baseline (1994), were 47-64 y of age, were free of
      cardiovascular diseases, diabetes mellitus and malignant neoplasmas, and
      completed a detailed lifestyle questionnaire. In addition, all participants
      completed a follow-up questionnaire in 1998. MEASUREMENTS: Baseline plasma leptin
      levels and 4-y weight change. RESULTS: At the start of follow-up, men in the
      highest quintile for plasma leptin (mean=12.1 ng/ml) weighed more, were less
      physically active, and had higher circulating insulin levels than men in the
      lowest quintile (mean=2.7 ng/ml). After adjustments for baseline age, weight,
      height, smoking status, alcohol intake, and physical activity, each 10 ng/ml
      increase in plasma leptin concentration was associated with a 1.68 kg (95% CI
      0.14-3.18 kg) weight gain over the 4-y follow-up period. The observed association
      between leptin level and weight gain was limited to men with a baseline body mass
      index (BMI) of > or =25 kg/m2, in whom a 10 ng/ml higher baseline leptin was
      associated with a 2.45 kg (95% CI 0.73-4.18-kg) weight gain. Further adjustments
      for baseline total energy intake, plasma insulin and soluble tumor necrosis
      factor receptors levels did not appreciably alter these results. Plasma insulin
      level was not independently associated with subsequent weight gain. CONCLUSION:
      These results suggest that elevated plasma leptin concentrations among overweight
      men may be a marker of leptin resistance and subsequent weight gain.

PMID- 11319632
TI  - Soft tissue concentrations of ciprofloxacin in obese and lean subjects following
      weight-adjusted dosing.
AB  - OBJECTIVE: To investigate whether weight adjusted ciprofloxacin dosing results in
      comparable target site concentrations in obese and lean subjects. DESIGN:
      Comparative study in two populations. SUBJECTS: Twelve obese subjects (mean
      weight 122+/-22.6 kg, 28-52 y, male&ratio;female ratio 4&ratio;8) and 12 age- and
      sex-matched lean controls (mean weight 59+/-8.6 kg). METHODS: Sampling of
      interstitial space fluid by means of calibrated in vivo microdialysis after a
      weight-adjusted intravenous bolus dose of 2.85 mg/kg ciprofloxacin. Analysis of
      drug concentration by high pressure liquid chromatography. RESULTS: We found
      significantly higher peak and trough levels of ciprofloxacin in plasma for obese
      subjects (9.97+/-5.64 and 0.44+/-0.10 microg/ml vs 2.59+/-1.06 and 0.19+/-0.09
      microg/ml in lean subjects, P<0.05), while concentration-time curves of
      interstitial fluid of muscle and subcutaneous fat did not differ between the
      groups. Tissue penetration, expressed as AUC(tissue)/AUC(plasma) ratio was
      significantly lower in obese subjects (0.45+/-0.27 vs 0.82+/-0.36, P<0.01).
      CONCLUSION: We conclude that the penetration process into the interstitial space
      fluid is impaired in obese subjects. Therefore antibiotic doses need not be
      adjusted for an increase in fat/water ratio. Weight-adjusted dosing based on
      actual body weight will yield adequate tissue levels for ciprofloxacin.

PMID- 11319633
TI  - The prediction of basal metabolic rate in female patients with anorexia nervosa.
AB  - OBJECTIVE: To evaluate in female patients with anorexia nervosa the accuracy of a
      specific predictive formula for basal metabolic rate (BMR) already proposed in
      the literature and to derive a new disease-specific equation with the same
      purpose. DESIGN: Cross-sectional study. SUBJECTS: One-hundred and twenty
      adolescent girls (<18 y) and young-adult women (18-30 y) with anorexia nervosa.
      MEASUREMENTS: BMR was determined by indirect calorimetry or predicted according
      to the Schebendach formula, which was specifically derived for anorexia nervosa.
      RESULTS: On average the Schebendach formula performed well in the adolescent
      group but not in the young-adult group. The range including 95% of the predicted
      measured differences was in both cases wider than 2000 kJ/day. In the young-adult
      patients the accuracy of the prediction was also related to age and body mass
      index. Weight and age (but not height or body mass index) emerged as predictors
      of BMR in the sample as a whole, and only weight when the two age groups were
      considered separately, thus leading to three different equations. The intercepts
      of these regression lines were very close and not significantly different from
      zero while their standard error of estimate was 500-550 kJ/day. CONCLUSION: The
      Schebendach formula is not very accurate in estimating the BMR of female
      anorectic patients. Moreover, in this group the relationship between BMR and
      weight was altered. The predictive formulas proposed by the present study have a
      reasonable prediction power.

PMID- 11319634
TI  - Night eating and nocturnal eating-two different or similar syndromes among obese
      patients?
AB  - OBJECTIVE: The main aim of this study was to identify subjects with (1) night
      eating syndrome (defined as morning anorexia, evening hyperphagia and insomnia)
      and (2) nocturnal eating syndrome (defined as eating at night after having gone
      to bed). In the literature the differences and similarities between these two
      syndromes are not clear. SUBJECTS: One-hundred and ninety-four obese patients
      from an academic, clinical obesity unit. Mean BMI (+/-s.d.) was 40+/-5 kg/m2, age
      44+/-12 y and 76% were women. MEASUREMENTS: Questionnaires with multiple choices
      and open questions along with the Binge Eating Scale. RESULTS: Fourteen percent
      of the patients met the criteria for night eating and/or nocturnal eating
      syndrome. Night eating syndrome was manifest in 6% of the patients and nocturnal
      eating syndrome in 10%. Both the night eaters and the nocturnal eaters had more
      trouble getting to sleep than the patients without night/nocturnal eating
      problems (P<0.001 and P<0.01). The nocturnal eaters also had more trouble staying
      asleep (P<0.001). Morning anorexia was not typically found in nocturnal eaters.
      Being on long-term sick leave was more common among the nocturnal eaters
      (P<0.01). CONCLUSION: Fourteen percent of the patients at our obesity unit met
      the criteria for night eating and/or nocturnal eating syndrome. There are clear
      similarities between night eating syndrome and nocturnal eating syndrome, but
      also differences.

PMID- 11319635
TI  - Relationship between dietary restraint, binge eating, and leptin in obese women.
AB  - OBJECTIVE: To describe some biological, behavioural and psychological correlates
      of the Three-Factor Eating Questionnaire, and to determine the relationship
      between dietary restraint, binge eating, and leptin among obese women seeking
      treatment. DESIGN: Consecutive series of obese women enrolled in a clinical
      program for weight reduction treatment. SUBJECTS: Forty-two obese women. Eight
      participants met the criteria for 'severe binge eating' as measured by the Binge
      Eating Scale. MEASUREMENTS: Energy intake, resting energy expenditure, body
      composition, leptin, restraint, disinhibition, hunger and binge eating were
      assessed before starting the treatment. RESULTS: In this sample both higher
      disinhibition and hunger scores were associated with greater binge eating
      severity. Obese women with severe binge eating had lower restraint, higher
      disinhibition and hunger scores, as well as higher daily fat intake, when
      compared with obese non-binge-eaters. Interestingly, restraint scores were
      negatively associated with leptin levels among subjects with severe binge eating.
      CONCLUSION: In obese women with severe binge eating, the negative relationship
      between dietary restraint and serum leptin concentrations seems mediated by a
      greater fat intake. These findings need to be verified in further human studies.

PMID- 11319636
TI  - Mechanism for obesity-induced increase in myocardial lipid peroxidation.
AB  - OBJECTIVE: To determine the mechanisms underlying the obesity-induced increase in
      myocardial lipid peroxidation in the fa/fa rat. We hypothesized that elevated
      heart work (ie rate-pressure product), an increased rate of superoxide (O2*-))
      production, total myocardial lipid content, and/or insufficient antioxidant
      defenses are potential contributors to myocardial lipid peroxidation in obesity.
      DESIGN: Comparative, experimental study of myocardial tissue in 16-week-old lean
      control (Fa/?, normal diet), obese high-fat fed (Fa/?, 45% dietary fat), and
      obese fatty (fa/fa, normal diet) Zucker rats. MEASUREMENTS: Myocardial work
      (heart rate x systolic blood pressure), myocardial lipid content, oxidative and
      antioxidant enzyme activities (citrate synthase (CS), catalase (CAT), glutathione
      peroxidase (GPX), superoxide dismutase (SOD)), the rate of papillary muscle
      superoxide radical production in vitro, thiol content, basal and post-oxidative
      challenge myocardial lipid peroxidation levels using thiobarbituric reactive acid
      substances (TBARS) and lipid hydroperoxides (PEROX) as indices of lipid
      peroxidation. RESULTS: Compared to lean controls, the high-fat fed and fatty
      animals had similar elevations (P<0.05) in myocardial TBARS and PEROX (23%, 25%
      and 29% 45%, respectively; P<0.05), and elevated susceptibilities to oxidative
      stress in vitro following exposure to oxidizing agents (P<0.05). Resting heart
      work was slightly higher (P<0.05) in both the high-fat fed and fatty animals
      compared to controls. Myocardial lipid content, SOD activities and non-protein
      thiol (glutathione) levels were elevated (P<0.05) in high-fat fed and fatty
      animals compared to controls. The rate of superoxide formation by isolated
      papillary muscles in vitro did not differ among groups (P<0.05). Regression
      analysis revealed that the myocardial lipid content contributed most to
      myocardial lipid peroxidation (R2=0.76, P<0.05). CONCLUSIONS: Myocardial
      oxidative injury is closely associated with myocardial lipid content, but is not
      closely correlated with heart work, insufficient antioxidant defenses or a
      greater rate of superoxide production.

PMID- 11319637
TI  - A social epidemiologic study of obesity among preschool children in Thailand.
AB  - OBJECTIVE: To describe the prevalence of childhood obesity in a moderately
      industrialized province in Thailand and examine the influence of socioeconomic
      status (SES) on childhood obesity. DESIGN: Cross-sectional study. SUBJECTS: One
      thousand one hundred and fifty seven children in the second or third grade of
      kindergartens in Saraburi Province, Thailand. MEASUREMENTS: Height and weight
      were measured and the weight-for-height index with the Thai national standard was
      used for assessing nutritional status. A questionnaire was used for measuring
      parents' socioeconomic status. RESULTS: The prevalence of childhood obesity over
      97th percentile for weight-for-height (>p(97)) was 22.7% in urban and 7.4% in
      rural areas. There were marked relationships between childhood obesity and
      parents' educational level and household income. CONCLUSION: Childhood obesity is
      an emerging health problem in developing countries, especially in urban areas.
      This study demonstrates a marked correlation between SES and prevalence of
      childhood obesity in an Asian developing country.

PMID- 11319638
TI  - Trends in BMI among Belgian children, adolescents and adults from 1969 to 1996.
AB  - OBJECTIVE: To document secular data on changes in the distribution of body mass
      index (BMI), to determine the probability of overweight at 40 y of age in Belgian
      males in relation to the presence or absence of overweight at different ages in
      adolescence, and to estimate tracking of BMI in Belgian males in Belgium aged 12
      40 y. DESIGN: Cross-sectional and mixed longitudinal surveys in nationally
      representative samples of Belgian males and females. SUBJECTS: Cross-sectional
      more than 21 000 boys and 9698 girls; to examine secular trends-3164 boys and
      5140 girls; to examine tracking-161 males. MEASURES: Body mass and height to
      determine BMI. RESULTS: In Belgian children the degree of overweight has
      increased between 1969 and 1993. Tracking of BMI is high in adolescence (r=0.77)
      and adulthood (r=0.69-0.91) and moderate from adolescence to adulthood (r=0.49).
      In Belgian males, the probability of overweight at 40 y of age in the presence of
      overweight at different ages in adolescence is important (odds ratios 5.0-6.9).
      CONCLUSIONS: Cross-sectional and longitudinal data, trends and tracking of BMI
      from 1969 until 1996 in Belgium indicate an increase in the degree of childhood
      overweight and obesity. Moreover, the risk of an overweight male adolescent
      becoming an overweight adult is substantial. Measures to restrict the Belgian
      overweight and obesity epidemic should be taken.

PMID- 11319639
TI  - Comparison of the body mass index to other methods of body fat evaluation in
      ethnic Japanese and Caucasian adolescent girls.
AB  - OBJECTIVE: The aim of this study was to assess the body mass index (BMI) and its
      relationship with other methods of body fat evaluation in pre- and post
      menarcheal, Japanese and Caucasian female adolescents, using two different cut
      off points for obesity: 28% and 30%. DESIGN: A cross-sectional study with
      incomplete sampling, using the subject as the evaluation unit. SUBJECTS: A total
      of 436 Japanese and Caucasian female adolescents in two age groups: 10-11 (pre
      menarcheal adolescent); and 16-17 (post-menarcheal adolescents). METHODS: For the
      BMI the cut-off point for thinness was set at the 5th percentile of the BMI
      distribution of the NCHS reference population and the cut-off point for
      overweight and obesity was set at the 85th percentile. Body composition was
      assessed using foot-to-foot bioelectrical impedance analysis (BIA), near-infrared
      interactance (NIR) and Slaughter skinfold equations (SKI). The statistical
      comparison of the methods was performed using the kappa agreement test and the
      McNemar disagreement test. RESULTS: In the 10- and 11-y-old girls, the BMI was
      considerably and significantly correlated with the other methods. The major
      agreements were: in Japanese adolescents BMI x NIR=82.3% (cut-off point of 28%),
      BMI x BIA=85.7% (cut-off point of 30%); in Caucasian adolescents BMI x NIR=80.7%
      (cut-off point of 28%), BMI x BIA=87.4% (cut-off point of 30%). The disagreement
      above the diagonal between BMI x NIR was higher within the two groups for both
      the cut-off points, revealing that the girls identified as obese by the BMI were
      considered eutrophic by NIR. In the 16- and 17-y-old adolescents, the BMI
      demonstrated low or no correlation with the other methods. Furthermore, it
      presented disagreements below the diagonal, revealing that the BMI identified
      fewer obese subjects than the other methods. CONCLUSION: Among the 10- and 11-y
      olds, the BMI presented a good correlation with the other methods, independent of
      ethnicity. The BMI can therefore be used in place of these methods, although it
      may underestimate obesity. Among the 16- and 17-y-olds, the BMI presented low or
      no agreement with the other methods, suggesting that it is probably not a
      suitable index for this age-group in studies focusing on the identification of
      obesity. In such cases the choice of one of the other methods, depending on
      availability, cost or technical experience, may represent a better approach.

PMID- 11319640
TI  - Prevalence of overweight in a triethnic pediatric population of San Antonio,
      Texas.
AB  - OBJECTIVES: To investigate the prevalence of overweight among different ethnic
      and gender groups of children and adolescents in the San Antonio, Texas, area and
      to compare the prevalence with that of the US national figures. DESIGN: Cross
      sectional study SUBJECTS: A total of 7208 schoolchildren in kindergarten through
      12th grade. There were 4215 Mexican American (MA) (58.5%), 2040 non-Hispanic
      white (NHW) (28.3%) and 953 African American (AA) (13.2%) subjects. MEASUREMENTS:
      Weight, height and skinfold thicknesses. RESULTS: The body mass index (BMI,
      kg/m2) values of MA boys were almost consistently and significantly (P<0.05)
      larger than NHW boys and showed a tendency to be larger than AA boys, beginning
      as early as age 6 and continuing through age 17. Although rarely significant, a
      similar trend in ethnic difference was also noted for girls, with the smallest
      BMI seen in NHW girls. The subscapular skinfold thickness (SST) for MA boys and
      girls was significantly (P<0.05) larger than that for NHW counterparts and showed
      a tendency to be larger than AA counterparts. No significant ethnic differences
      were present in the triceps skinfold thickness (TST) for girls, but MA boys' TST
      were occasionally larger (P<0.05) than other ethnic-gender groups. Girls' TST
      were frequently larger (P<0.05) than boys for each ethnic groups. Using the
      population data from the National Health and Nutrition Examination Survey
      (NHANES) I as reference, the prevalence of overweight (BMI> or =95th percentile)
      was greater in MA (15-28%) and AA (11-29%) boys and girls than in NHW (7-17%)
      counterparts. The combined prevalence of overweight and 'at risk of overweight'
      (BMI>85th percentile) was much larger in MA boys (40-50%), MA girls (34-52%), and
      AA girls (33-51%) than other subgroups. The onset of overweight is quite early,
      starting at 5-6 y of age, especially in girls. Compared to the data from national
      surveys, the prevalence of overweight found in this study is higher than reported
      nationally. We found a marked increase in the skinfold thickness, especially SST
      for boys, but the increase is less for girls. CONCLUSIONS: The prevalence of
      overweight is higher in MA boys and girls and AA girls than other ethnic-gender
      groups in the San Antonio, Texas, area. The prevalence of childhood overweight in
      the San Antonio area is higher than national figures. The findings of increasing
      prevalence and early onset of childhood overweight are concerning, because these
      are known risk factors for diabetes and diseases of many other organ systems.
      Measures to prevent, reduce or treat childhood obesity are urgently needed.

PMID- 11319641
TI  - Fat balance and serum leptin concentrations in normal, hypothyroid, and
      hyperthyroid rats.
AB  - OBJECTIVE: To study the influence of thyroid hormones on the relationship between
      serum leptin and fat mass, as well as on energy and macronutrient balance.
      DESIGN: Rats with different thyroid states were obtained by 7 and 15 days of
      treatment with the antithyroid drug propylthiouracil or with triiodothyronine
      (T3). MEASUREMENTS: Energy balance, macronutrient balance and serum leptin
      concentrations. RESULTS: In hypothyroid rats we found a decrease in metabolizable
      energy (ME) intake and energy expenditure together with an increase in lipid
      gain/lipid intake ratio and a decrease in protein gain/protein intake ratio.
      Consequently, body lipid percentage significantly increased compared to euthyroid
      rats. Hyperthyroid rats first increased energy expenditure and later ME intake,
      so that increased metabolism was balanced by increased intake, and energy gain
      was similar to that found in euthyroid rats. CONCLUSION: These results indicate
      that T3 plays a major role in the maintenance of energy and lipid balance. Our
      results also indicate that an inverse relationship exists between T3 and leptin
      serum concentrations, and that this relationship is not only the result of
      changes in body fat stores induced by changed T3 concentrations.

PMID- 11319642
TI  - Decreased lipolysis and enhanced glycerol and glucose utilization by adipose
      tissue prior to development of obesity in monosodium glutamate (MSG) treated
      rats.
AB  - OBJECTIVE: To determine the metabolic alterations that lead to the neonatal
      administration of monosodium glutamate (MSG), which results in arrested growth
      and obesity. ANIMALS AND DESIGN: Wistar rats were injected 5 times, every other
      day, with 4 g of MSG/kg b.w. or with hyperosmotic saline (controls), within the
      first 10 days of life, and were studied at the age of 30 days. RESULTS: Body
      weight was lower, whereas adipocyte lipid content, cell diameter, surface area
      and volume were higher in MSG rats than in controls. Plasma glucose, insulin,
      NEFA, glycerol and triglyceride levels, and in vitro production of NEFA by lumbar
      fat pad pieces incubated under basal conditions or in the presence of epinephrine
      and epinephrine plus glucose in the media were lower in MSG than in control rats.
      In the same fat pad pieces, the conversion of 1-14C-glycerol into fatty acids was
      always enhanced and its conversion into glyceride glycerol was enhanced when
      incubations were carried out in the presence of epinephrine or glucose. Both the
      hormone sensitive lipase activity and mRNA expression were lower in adipose
      tissue from MSG rats. Besides, the number of insulin receptors, lipid synthesis
      from U14C glucose, 3H-2-deoxy D-glucose uptake and cellular GLUT4 translocation
      index were higher in adipocytes from MSG rats than from the controls. CONCLUSION:
      It is proposed that an enhanced insulin sensitivity in 1 month old MSG rats is
      responsible for the decreased lipolytic activity and enhanced glucose uptake. In
      addition, the enhanced lipogenesis and glycerol reutilization seen in their
      adipose tissue, disturbs the normal balance between fat depots breakdown and
      accumulation in favor of the latter.

PMID- 11319643
TI  - Different origin of hypertriglyceridemia induced by a high-fat and a high-sucrose
      diet in ventromedial hypothalamic-lesioned obese and normal rats.
AB  - OBJECTIVE: To clarify the mechanism by which plasma triacylglycerol is affected
      by a high fat or a sucrose diet. DESIGN: Two sets of six groups each having six
      rats were prepared-(1) ventromedial hypothalamic (VMH)-lesioned rats fed a
      standard diet; (2) sham VMH-lesioned rats fed a standard diet; (3) VMH-lesioned
      rats fed a high-fat diet; (4) sham VMH-lesioned rats fed a high-fat diet; (5) VMH
      lesioned rats fed a high-sucrose diet; and (6) sham VMH-lesioned rats fed a high
      sucrose diet. After VMH lesions and sham operations, the rats were provided
      standard, high-fat and high sucrose diets for 2 weeks. Two weeks later, blood
      samples were collected after overnight fast to determine plasma triacylglycerol
      (TAG), hepatic triacylglycerol secretion rate (TGSR), fractional catabolic rate
      (FCR) of triacylglycerol and postheparin plasma lipoprotein lipase (LPL), plasma
      glucose, insulin and leptin. RESULTS: Values of TAG, TGSR, FCR and LPL in VMH
      lesioned obese rats were all greater than those in sham-operated rats, regardless
      of the diet fed. In sham-operated rats, high-fat diet fed rats showed higher TAG
      with similar TGSR, higher LPL and lower FCR than those of standard diet fed rats.
      High-sucrose diet fed rats showed significantly higher TAG with higher TGSR,
      higher LPL and lower FCR than those of standard diet fed rats. Moreover, high
      sucrose diet fed rats showed higher TAG with higher TGSR, lower LPL and higher
      FCR than those of high-fat diet fed rats. In VMH-lesioned rats, high-fat diet fed
      rats showed higher TAG with similar TGSR, higher LPL and lower FCR than those of
      standard diet fed rats. High-sucrose diet fed rats showed markedly higher TAG
      with notably higher TGSR, higher LPL and lower FCR than those of standard diet
      fed rats. High-sucrose diet fed rats showed still higher TAG with markedly higher
      TGSR, similar LPL and higher FCR than those of high-fat diet fed rats.
      CONCLUSIONS: The mechanism by which TAG metabolism is affected by a high-fat or a
      high-sucrose diet differed; a high-fat diet increased plasma TAG level by
      lowering removal of TAG without increase in hepatic TAG secretion in sham
      operated (normal) rats. A high-sucrose diet, in contrast, induced much higher
      plasma TAG levels by both increased hepatic TAG secretion and decreased removal
      of TAG. The effects of a high-fat or a high-sucrose diet were similar but
      exaggerated in VMH lesioned animals.

PMID- 11319644
TI  - Validation of dual energy X-ray absorptiometry (DXA) by comparison with chemical
      analysis of dogs and cats.
AB  - BACKGROUND: Dual-energy X-ray absorptiometry (DXA) has been used extensively to
      measure body composition, but has been validated by comparison to chemical
      analysis on relatively few occasions. Moreover, these previous validation studies
      have ground up entire carcasses prior to chemical analysis, thus potentially
      obscuring sources of error in the DXA analysis. OBJECTIVE: The purpose of this
      study was to validate DXA by comparison to chemical analysis in dogs and cats,
      performing chemical analysis on dissected rather than ground carcasses to reveal
      sources of discrepancy between the two methods. DESIGN: Sixteen animals (10 cats
      and 6 dogs weighing between 1.8 and 22.1 kg) were scanned by DXA post-mortem
      using a Hologic QDR-1000 W pencil beam machine and then dissected into 22
      separate components. Individual tissues were dried and then sub-sampled for
      analysis of fat content by Soxholet extraction, or ashing in a muffle furnace.
      Body composition by DXA was compared to body composition by chemical analysis and
      discrepancies between the two correlated with chemical composition of individual
      tissues. We also explored the capability of the machine to establish the fat
      contents of mixtures of ground beef, lard and water. RESULTS: DXA estimates were
      strongly correlated with estimates derived from chemical analysis: total body
      mass (r=1.00), lean tissue mass (r=0.999), body water content (r=0.992) and fat
      mass (r=0.982). Across individuals the absolute and percentage discrepancies were
      also small: total body mass (13.2 g, 1.02%), lean tissue mass (119.4 g, 2.64%),
      water content (101 g, 1.57%) and fat content (28.5 g, 2.04%), where the
      percentage error is expressed relative to the average mass of that component
      across all individuals. Although on average DXA compared very well to chemical
      analysis, individual errors were much greater. Individual errors in the lean
      tissue and fat tissue components were strongly correlated with the fat content of
      skeletal muscle and the lean content of mesenteric fat. The error in the DXA
      estimate of total fat content was related to skeletal muscle hydration.
      Experimental studies using mixtures of lean ground beef, water and lard indicated
      that tissue hydration may have important effects on the perception of tissue fat
      content by DXA. Bone mineral content by DXA was approximately 30% lower than
      whole body ash content but only 7.7% lower than ash content of the bones.
      CONCLUSIONS: On average pencil beam DXA analysis using the Hologic QDR-1000 W
      machine provides an accurate estimate of body composition in subjects weighing
      between 1.8 and 22.1 kg. Individual discrepancies, however, can be large and
      appear to be related to lean tissue hydration.

PMID- 11319645
TI  - Fiber type dependent upregulation of human skeletal muscle UCP2 and UCP3 mRNA
      expression by high-fat diet.
AB  - OBJECTIVE: To test the hypothesis that consumption of a high-fat diet leads to an
      increase in UCP mRNA expression in human skeletal muscle. In a group of endurance
      athletes, with a range in fiber type distribution, we hypothesized that the
      effect of the high-fat diet on UCP2 and UCP3 mRNA expression is more pronounced
      in muscle fibers which are known to have a high capacity to shift from
      carbohydrate to fat oxidation (type IIA fibers). DESIGN: Ten healthy trained
      athletes (five males, five females) consumed a low-fat diet (17+/-0.9 en% of fat)
      and high-fat diet (41.4+/-1.4 en% fat) for 4 weeks, separated by a 4 week wash
      out period. Muscle biopsies were collected at the end of both dietary periods.
      MEASUREMENTS: Using RT-PCR, levels of UCP2 and UCP3 mRNA expression were measured
      and the percentage of type I, IIA and IIB fibers were determined using the
      myofibrillar ATPase method in all subjects. RESULTS: UCP3L mRNA expression tended
      to be higher on the high-fat diet, an effect which reached significance when only
      males were considered (P=0.037). Furthermore, diet-induced change in mRNA
      expression of UCP3T (r: 0.66, P=0.037), UCP3L (r: 0.61, P=0.06) and UCP2 (r:
      0.70, P=0.025), but not UCP3S, correlated significantly with percentage dietary
      fat on the high-fat diet. Plasma FFA levels were not different during the two
      diets. Finally, the percentage of type IIA fibers was positively correlated with
      the diet-induced change in mRNA expression for UCP2 (r: 0.7, P=0.03), UCP3L (r:
      0.73, P=0.016) and UCP3T (r: 0.68, P=0.03) but not with UCP3S (r: 0.06, NS).
      CONCLUSION: UCP2 and UCP3 mRNAs are upregulated by a high-fat diet. This
      upregulation is more pronounced in humans with high proportions of type IIA
      fibers, suggesting a role for UCPs in lipid utilization.

PMID- 11319646
TI  - In-vivo quantitative hydrolipidic map of perirenal adipose tissue by chemical
      shift imaging at 4.7 Tesla.
AB  - OBJECTIVE: In this work, chemical shift magnetic resonance imaging is used for in
      vivo quantitative evaluation of fat and water content in the perirenal white
      adipose tissue. DESIGN AND MEASUREMENTS: Experiments were carried out on female
      Sprague-Dawley rats with a 4.7 T magnet. Fat and water fractions were computed
      pixel-by-pixel from the chemical shift selective images with an algorithm of
      reconstruction that allowed parametric maps (called hydrolipidic maps) to be
      produced with a pixel size of 625 x 625 microm. RESULTS: Our findings indicate
      that, in the perirenal adipose tissue, the water content ranges between 15% and
      20%, with slight differences between the ventral and dorsal portions, and between
      the left and right deposits. The mesenteric adipose tissue, observed for
      comparison, has a mean water content of 30%. CONCLUSION: The present work
      demonstrates that methods based on magnetic resonance imaging can be useful tools
      for non-invasive in vivo quantitative mapping of the hydrolipidic content of
      adipose tissues.

PMID- 11319647
TI  - Genetic variation in the stress protein hsp70-2 gene is highly associated with
      obesity.
AB  - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) expression is increased in
      adipose tissue of both rodent models of obesity and obese humans. It has
      therefore been considered as a candidate gene for obesity. Several studies have
      indeed shown statistical evidence of linkage between obesity and the chromosomal
      region encompassing the TNF-alpha gene, suggesting that TNF-alpha and/or a nearby
      gene (eg hsp70 gene) is involved in the onset and progression of weight gain. We
      designed a case-controlled study to investigate the potential association of
      polymorphism of the TNF-alpha and that of a stress protein (hsp70-2) with
      obesity. METHODS: We used the polymerase chain reaction and restriction enzyme
      digestion to characterize the variation of the TNF-alpha promoter region and that
      of the hsp70-2 gene in 343 unrelated Tunisian patients with obesity and 174
      healthy control subjects. RESULTS: Analysis of the -308 TNF-alpha polymorphism in
      patients with obesity and in control subjects did not reveal an association
      between TNF-alpha alleles and obesity. In contrast, polymorphism analysis of the
      hsp70-2 gene in patients with obesity demonstrated highly significant differences
      in genotypic distribution of this bi-allelic locus compared to the control
      subject group. Homozygosity for one hsp70-2 allele was highly associated with
      obesity (r2=7.12; P<10(-6)). CONCLUSION: Tunisian persons carrying the P2/P2
      genotype of the hsp70-2 gene may have an increased risk of obesity.

PMID- 11319648
TI  - The association between the val/ala-55 polymorphism of the uncoupling protein 2
      gene and exercise efficiency.
AB  - BACKGROUND: Energy expenditure may partly be determined by genetic variations in
      uncoupling proteins. We have previously found an increased physical activity but
      a similar 24-h energy expenditure (EE) in subjects with the val/val-55 UCP2
      genotype compared to those with the ala/ala genotype which indicates that the val
      55 allele is statistically associated with a higher metabolic efficiency. DESIGN:
      EE during bicycling was determined by indirect calorimetry at three different
      loads (30, 40 and 60% of VO2max in eight subjects with the val/val-55 genotype
      (35+/-6 y weight=76.8+/-13.6 kg, VO2max=2.79+/-0.71 l/min) and eight subjects
      with the ala/ala-55 genotype (37+/-3 y, weight=78.3+/-16.5 kg, VO2max=2.66+/-0.41
      l/min). RESULTS: Incremental exercise efficiency across the three different work
      levels was higher in the val/val (25.3%, c.i. 24.2-26.4%) than in the ala/ala
      (23.6%, c.i. 22.5-24.7%) genotype P<0.05. Gross exercise efficiency at 40% VO2max
      was higher in the val/val (15.3+/-0.6%) than in the ala/ala (13.5+/-0.4%) group.
      CONCLUSION: As the val/ala-55 polymorphism is located in a domain of the protein
      without any known function, the different exercise efficiency between the two
      genotypes most likely reflects a linkage disequilibrium with a functionally
      significant polymorphism in UCP2 or in the neighbouring UCP3 gene. The study
      suggests that variations in the UCP genes may affect not only basal metabolic
      rate but also influence energy costs of exercise.

PMID- 11319649
TI  - Uncoupling protein 3 genetic variants in human obesity: the c-55t promoter
      polymorphism is negatively correlated with body mass index in a UK Caucasian
      population.
AB  - OBJECTIVE: To investigate whether genetic variation at the UCP3 locus contributes
      to human obesity. SUBJECTS: Ninety-one obese children (BMI>4 standard deviations
      from age related mean) and 419 Caucasian adults from the Isle of Ely Study.
      DESIGN: Single strand conformation polymorphism (SSCP) analysis was used to scan
      the coding region of the UCP3 gene in 91 severely obese children. A common
      polymorphism identified in this gene (c-55t) has been shown to associate with
      lower UCP3 mRNA expression. Polymerase chain reaction-based forced restriction
      digestion was used to detect this allele in Caucasian adults. Multiple regression
      analysis was used to determine associations between the c-55t genotype and
      anthropometric, energetic and biochemical indices relevant to obesity.
      MEASUREMENTS: For the obese children, SSCP analysis and sequencing of variants
      were carried out. For the Isle of Ely Study, c-55t genotype and anthropometric
      (body mass index, waist-hip ratio, percentage body fat), energetic (dietary fat
      intake, physical activity index, adjusted metabolic rate, maximum oxygen
      consumption) and biochemical indices (pre- and post-glucose challenge plasma
      triglycerides, non-esterified fatty acids, insulin and glucose) were determined.
      RESULTS: A previously reported missense mutation (V102I) was detected in a single
      obese Afro-Carribean child. Twenty-one percent of the genes examined in the Isle
      of Ely study carried the c-55t promoter variant. Age-adjusted body mass index
      (BMI) was significantly (P=0.0037) lower in carriers of this variant. CONCLUSION:
      Mutations in the coding sequence of UCP3 are unlikely to be a common monogenic
      cause of severe human obesity. In a Caucasian population the UCP3 c-55t
      polymorphism is negatively associated with BMI.

PMID- 11319650
TI  - Sibutramine metabolites increase glucose transport by cultured rat muscle cells.
AB  - BACKGROUND: The anti-obesity agent sibutramine, a serotonin and noradrenaline
      reuptake inhibitor (SNRI), has been shown to reduce insulin resistance and
      improve glycaemic control in obese-diabetic ob/ob mice and overweight type 2
      diabetic patients. OBJECTIVE: To investigate whether sibutramine or its
      metabolites act directly on muscle cells to improve glucose uptake and insulin
      action. DESIGN: Uptake of the non-metabolized glucose analogue 2-deoxyglucose was
      measured in cultured L6 rat muscle cells after incubation with sibutramine, its
      two pharmacologically active metabolites and related agents. RESULTS: Sibutramine
      itself (10(-8)-10(-6) M) did not significantly affect 2-deoxyglucose uptake
      during incubations up to 72 h. The primary amine metabolite M2 (10(-7) and 10(-6)
      M) increased basal and insulin-stimulated 2-deoxyglucose uptake (by 12% and 34%)
      after 24 h incubation. These effects of M2 were lost by 72 h incubation. However,
      the secondary amine metabolite M1 (10(-6) M) increased basal and insulin
      stimulated 2-deoxyglucose uptake (by 50%) after 72 h incubation, although M1 was
      ineffective after 24 h. M2 stimulated 2-deoxyglucose uptake in the presence of LY
      294,002 (an inhibitor of phosphatidylinositol 3-kinase) but the effect of M2 was
      inhibited by cytochalasin B, which acutely blocks glucose transporters.
      Incubations with serotoninergic, noradrenergic and dopaminergic agents, or agents
      known to stimulate release or inhibit reuptake of these substances in nervous
      tissues indicated that the sibutramine metabolites were not affecting 2
      deoxyglucose uptake via mechanisms associated with their SNRI properties.
      CONCLUSIONS: Sibutramine metabolites can improve insulin-sensitive 2-deoxyglucose
      uptake by cultured muscle cells independently of SNRI effects.

PMID- 11319651
TI  - Continuous negative abdominal pressure device to treat pseudotumor cerebri.
AB  - OBJECTIVE: To study the effects of an externally applied negative abdominal
      pressure device designed to lower the effects of intra-abdominal pressure (IAP)
      on headaches and pulsatile tinnitus in severely obese women with pseudotumor
      cerebri (PTC). DESIGN: Short-term clinical intervention trial in the Clinical
      Research Center. Days 1 and 3 were 'control' days; on days 2 and 4-6 patients
      were in the device from 8:00 am to noon and from 1:00 to 5:00 pm, and on nights 7
      11 they were in the device from 10:00 pm to 8:00 am. The last four patients were
      treated in a device with a counter-traction mechanism. SUBJECTS: Seven centrally
      obese women with PTC. MEASUREMENTS: Headache and pulsatile tinnitus severity were
      graded by the patient using visual analog scale (1-10) and averaged for the time
      that the device was in use or not in use. IAP was estimated from urinary bladder
      pressure (UBP) before and during device use. The internal jugular vein (IJV)
      elliptical cross-sectional area was measured with B-mode ultrasonography; the
      timed average velocity was measured by Doppler. RESULTS: There was a decrease in
      both headache (6.8+/-0.8 to 4.2+/-0.8, P<0.05) and pulsatile tinnitus (4.2+/-0.5
      to 1.8+/-0.5, P<0.02) within 5 min, and in headache (to 2.2+/-0.8, P<0.01) and
      tinnitus (to 1.7+/-0.5, P<0.01) within 1 h of device activation. UBP decreased
      (P<0.001) from 19.1+/-3 to 12.5+/-2.8 cmH2O. Headache remained improved
      throughout time that the device was used. During the second week, five of seven
      patients slept in the device without difficulty and four awoke without headache.
      There was a progressive decrease (P<0.01) in headache during the day after
      sleeping in the device at night as compared with days 1 and 3 when it was not
      used (6.5+/-0.5, day 1; 4.1+/-0.7, day 3; 3.1+/-0.8, day 8; 2.3+/-0.8, day 10).
      Headaches returned late in the afternoon in two patients; the device was
      reactivated and headache again improved. Five patients underwent IJV sonography;
      the IJV area decreased (129+/-53 to 100+/-44 mm2, P=0.06) without a change in IJV
      flow (1004+/-802 to 1000+/-589 ml/min) with the device. When activated, the
      device was pulled into the patient, creating discomfort that was alleviated with
      the counter-traction mechanism in the last four patients. One patient developed a
      5 cm area of blisters that resolved when the device was worn over a hospital
      gown. CONCLUSIONS: Decreasing IAP relieved headaches and pulsatile tinnitus in
      PTC. When patients slept in the device, they awoke without headache or tinnitus,
      which remained markedly improved throughout most of the following day. This study
      supports the hypothesis that PTC in obese women is secondary to an increased IAP.

PMID- 11319652
TI  - Relatively low serum leptin levels in adults born with intra-uterine growth
      retardation.
AB  - BACKGROUND: In-utero under-nutrition dramatically alters the development of
      adipose tissue, during the fetal and the neonatal period. THE AIM OF THE STUDY:
      To investigate whether adults born with intra-uterine growth retardation (IUGR)
      show evidence of impaired adipose tissue development and leptin regulation.
      DESIGN: Serum leptin concentrations were measured in 26 healthy adults born with
      IUGR and 25 controls aged 24 y who have been studied previously, 3 y ago.
      RESULTS: The IUGR group demonstrated a significant increase of body mass index
      (BMI) in comparison to controls between 21 and 24 y of age (4.8+/-7.7%, P=0.004
      vs 0.8+/-6.7%, P=0.70). Percentage of total body fat mass was significantly
      higher in IUGR-born subjects than in controls (27.2+/-7.6 vs 22.0+/-7.3%,
      P=0.02). Fasting insulin was significantly higher in the IUGR group (7.5+/-3.8 vs
      5.3+/-2.3 miccroU/ml, P=0.03). Surprisingly, crude serum leptin concentrations
      did not significantly differ between the two groups. Moreover, adjusted means of
      serum leptin levels were significantly lower in IUGR-born subjects than in
      controls when corrected for body fat mass, gender and fasting insulin (11.3 vs
      13.8 ng/ml, P=0.02). SUMMARY: Adults born with IUGR developed an excess of
      adipose tissue associated with relatively low serum leptin levels suggestive of
      an altered adipocyte function. Considering the close relationship between adipose
      tissue and insulin-sensitivity, these observations point to the potential
      implication of abnormal adipose tissue development in the long-term metabolic
      consequences associated with in-utero undernutrition.

PMID- 11319653
TI  - Predictors of weight loss and maintenance during 2 years of treatment by
      sibutramine in obesity. Results from the European multi-centre STORM trial.
      Sibutramine Trial of Obesity Reduction and Maintenance.
AB  - BACKGROUND: In this report we assess pre-treatment determinants of weight loss
      and maintenance outcome in The Sibutramine Trial of Obesity Reduction and
      Maintenance (STORM), a 2 y randomized, double-blind, placebo-controlled, European
      multicenter study examining the effect of sibutramine (Sib) on inducing and
      maintaining weight loss in obese subjects. MATERIAL: A total of 605 obese
      patients (BMI: 30-45 kg/m2) of both gender were included from eight European
      centers and treated for 24 months. The patients were treated for the initial 6
      months by Sib (10 mg/day) and a low-fat low-energy, individualized diet (600
      kcal/day deficit). The 467 patients who achieved >5% weight loss after 6 months
      were randomized 3&ratio;1 to Sib (10 mg/day) (Sib/Sib) and placebo (Sib/Pla) for
      weight maintenance over a further 18 months. MAIN OUTCOME AND ANALYSES: Pre
      treatment individual characteristics were assessed as predictors of 6 months
      weight loss (kg) and 24 months weight maintenance using simple and multivariate
      correlation and regression analyses. RESULTS: In univariate analyses, the 6 month
      weight loss (n=505) was positively associated with pre-treatment body weight
      (r=0.27), height (r=0.18), fat-free mass (r=0.21) (all P<0.001), fat mass
      (r=0.13, P<0.03), and resting metabolic rate (r=0.13, P<0.003). However, no
      relation was found with age, gender, smoking status, age at onset of obesity, or
      number of previous slimming attempts. The same predictors were found for weight
      change to endpoint in the Sib/Sib group (n=350), while no predictors were
      identified in the Sib/Pla (n=114). In the multivariate regression analysis only
      pre-treatment body weight predicted weight loss at 6 months (P<0.001). Weight
      change (kg) to 24 month was predicted by: 4.34+0.07*body weight (kg)-4*treatment
      (Sib=1, Pla=0)-0.06*age (y), (r2=8%, P<0.001). CONCLUSION: Only pre-treatment
      body weight seems to be an important independent predictor of 6 months weight
      loss and 24 month weight maintenance in this study on diet and Sib. As only 8% of
      the variation in 24 months weight change could be explained by the predictors,
      the clinical value of this information is limited.

PMID- 11319654
TI  - Assessing abdominal fatness with local bioimpedance analysis: basics and
      experimental findings.
AB  - OBJECTIVE: Abdominal fat is of major importance in terms of body fat distribution
      but is poorly reflected in conventional body impedance measurements. We developed
      a new technique for assessing the abdominal subcutaneous fat layer thickness
      (SFL) with single-frequency determination of the electrical impedance across the
      waist (SAI). SUBJECTS AND MEASUREMENTS: The method uses a tetrapolar arrangement
      of surface electrodes which are placed symmetrically to the umbilicus in a plane
      perpendicular to the body axis. Twenty-four test subjects (12 male, 12 female)
      underwent SAI and abdominal magnetic resonance imaging (MRI). The SFL below the
      sensing electrodes was determined from MRI and correlated with the SAI data at
      four different frequencies (5, 20, 50 and 204 kHz). RESULTS: A highly significant
      linear correlation (r2=0.99) between SFL and SAI over a wide range of the
      abdominal SFL was found. Separate regression models for female and male subjects
      did not differ significantly, except at 50 kHz. CONCLUSION: SAI represents a good
      predictor of the SFL and provides an excellent tool for the assessment of central
      obesity.

PMID- 11319655
TI  - Relationships between physical activity, obesity and diabetes mellitus in a
      French elderly population: the POLA study. Pathologies Oculaires liees a l' Age.
AB  - OBJECTIVE: To analyse the relationships between body mass index, waist
      circumference, waist-to-hip ratio, physical activity and the risk of type 2
      diabetes in a French elderly population. DESIGN AND SUBJECTS: We conducted a
      cross-sectional study on 1113 men and 1419 women aged 60 y or more, participating
      in the POLA Study. RESULTS: The prevalence of diabetes was two-fold higher in men
      than in women (19.1% and 9.3%, respectively). The anthropometric variables
      studied-body mass index (BMI), waist circumference (WC) and the waist/hip ratio
      (WHR)-were all positively related to the prevalence of type 2 diabetes. The
      strongest relationships were found for BMI in men and WHR in women. In both
      genders, sport activity and diabetes were inversely linked whereas no
      relationship was shown between the amount of household activity and diabetes
      mellitus. CONCLUSION: In the elderly, overall obesity in men and abdominal fat
      accumulation in women appeared strongly related to diabetes. Sport activity was
      negatively and independently associated with the prevalence of diabetes mellitus.

PMID- 11319656
TI  - Compared with nibbling, neither gorging nor a morning fast affect short-term
      energy balance in obese patients in a chamber calorimeter.
AB  - OBJECTIVE: To test if a diet of 4.2 MJ/24 h as six isocaloric meals would result
      in a lower subsequent energy intake, or greater energy output than (a) 4.2 MJ/24
      h as two isocaloric meals or (b) a morning fast followed by free access to food.
      DESIGN: Subjects were confined to the Metabolic Unit from 19:00 h on day 1 to
      09:30 h on day 6. Each day they had a fixed diet providing 4.2 MJ with three
      pairs of meal patterns which were offered in random sequence. They were: six
      meals vs two meals without access to additional foods (6vs2), or six meals vs 2
      meals with access to additional food (6+vs2+), or six meals vs four meals
      (6+vsAMFAST). In the AMFAST condition the first two meals of the day were omitted
      to reduce daily intake to 2.8 MJ and to create a morning fast, but additional
      food was accessible thereafter. Patients were confined in the chamber calorimeter
      from 19:00 h on day 2 until 09:00 h on day 4, and then from 19:00 h on day 4 to
      09:00 h on day 6. The order in which each meal pattern was offered was balanced
      over time. MEASUREMENTS: Energy expenditure (chamber calorimetry), spontaneous
      activity (video) and energy intake (where additional foods were available) during
      the final 24 h of each dietary component. SUBJECTS: Ten (6vs2), eight (6+vs2+)
      and eight (6+vsAMFAST) women were recruited who had a BMI of greater than 25
      kg/m2. RESULTS: From experiment 6vs2 the difference between energy expenditure
      with six meals (10.00 MJ) and two meals (9.96 MJ) was not significant (P=0.88).
      Energy expenditure between 23:00 h and 08:00 h ('night') was, however,
      significantly higher (P=0.02) with two meals (9.12 MJ/24 h) compared with six
      meals (8.34 MJ/24 h). The pattern of spontaneous physical activity did not differ
      significantly between these two meal patterns (P>0.05). Total energy intake was
      affected by neither meal frequency in experiment 6+vs2+ (10.75 MJ with six, 11.08
      MJ with two; P=0.58) nor a morning fast in experiment 6+vsAMFAST (8.55 MJ/24 h
      with six, 7.60 MJ with AMFAST; P=0.40). The total diet of subjects who had a
      morning fast tended to have a lower percentage of total energy from carbohydrate
      (40%) than when they had six meals per 24 h (49%) (P=0.05). Subsequent energy
      balance was affected by neither meal frequency (6vs2; P=0.88, 6+vs2+; P=0.50) nor
      a morning fast (P=0.18). CONCLUSIONS: In the short term, meal frequency and a
      period of fasting have no major impact on energy intake or expenditure but energy
      expenditure is delayed with a lower meal frequency compared with a higher meal
      frequency. This might be attributed to the thermogenic effect of food continuing
      into the night when a later, larger meal is given. A morning fast resulted in a
      diet which tended to have a lower percentage of energy from carbohydrate than
      with no fast.

PMID- 11319657
TI  - Effects of short-term energy restriction and physical training on haemostatic
      risk factors for coronary heart disease in obese children and adolescents.
AB  - OBJECTIVE: To study the changes of haemostatic risk factors for coronary heart
      disease during a weight reduction programme in obese children and adolescents.
      DESIGN: A short-term longitudinal study. SUBJECTS: Thirty-seven obese white girls
      (age, 12+/-1.8 y; body mass index (BMI), 26.9+/-5.25) and 19 obese white boys
      (age, 11.9+/-1.7 y; BMI, 26.2+/-5.2). MEASUREMENTS: Fibrinogen, factor VII
      coagulant activity, von Willebrand factor antigen, and soluble P-selectin were
      determined before and after a 3 week programme including energy restriction and
      physical activities. RESULTS: All determined haemostatic risk factors decreased
      significantly during the programme. Changes in risk factors were correlated to
      changes in body composition. Children and adolescents with the highest initial
      concentrations showed the greatest decreases. CONCLUSION: Energy restriction
      combined with physical activity improves the haemostatic risk profile in obese
      children and adolescents.

PMID- 11319658
TI  - A twin study of weight loss and metabolic efficiency.
AB  - OBJECTIVE: To assess the genetic contribution to determinants of therapeutic
      weight loss in obese female identical twins. DESIGN: Subjects were studied for 40
      days on an inpatient unit in three phases: 7 baseline days; 28 days of weight
      reduction by a very low calorie diet (1.6 MJ per day); and 5 days after weight
      reduction. SUBJECTS: Fourteen pairs of premenopausal obese female identical twins
      (age: 39.0+/-1.7 y; body weight (BW): 93.9+/-21.2 kg; body mass index (BMI):
      34.2+/-7.8 kg/m2). MEASUREMENTS: : Body composition by hydrodensitometry and
      resting metabolic rate by indirect calorimetry were assessed before and after
      weight loss. RESULTS: : There was great variability among pairs in loss of weight
      (5.9-12.4 kg) and body fat (3.1-12.4 kg). By contrast, the intraclass correlation
      (ICC) within twin pairs was 0.85, P<0.001 for weight and 0.88, P<0.001 for body
      fat. A measure of metabolic efficiency, calculated as the difference between
      'estimated' and 'measured' energy deficit showed high intrapair correlation
      (ICC=0.77; P<0.001). CONCLUSIONS: The high correlation in metabolic efficiency
      within twin pairs in response to therapeutic weight loss suggests a strong
      genetic contribution.

PMID- 11319659
TI  - Interrelationship between insulin, leptin and growth hormone in growth hormone
      treated children.
AB  - OBJECTIVES: The aim of the study was to examine insulin homeostasis during growth
      hormone (GH) therapy, and to investigate the effect of GH treatment on insulin
      and leptin concentration in obese children. SUBJECTS: Nineteen obese children (8
      with Prader-Willi Syndrome (PWS)) were treated with GH 0.1 IU/kg/day dose for 3
      months and were compared with 29 non-treated age and sex matched obese children
      (9 PWS) and 49 GH treated non-obese short children. Mean age of the children was
      10.3+/-1.8 (6.7-13.8) y, with body mass index of 23.6+/-10.4 (11.5-47) kg/m2.
      RESULTS: Leptin concentration decreased and was correlated inversely with initial
      leptin value (r2=-0.374, P<0.001) and decreased body mass (r2=0.338, P=0.001).
      Insulin sensitivity index was not significantly changed during therapy. Leptin
      decrease after 3 months of GH administration was correlated inversely with the
      increase in first phase insulin response to intravenous glucose tolerance test
      (IVGTT) (r2=-0.595, P<0.001). Results of long-term follow-up of treated patients
      demonstrated a decrease in insulin concentration after cessation of therapy. In
      GH-treated subjects, the glucose increase in response to glucose load appeared to
      be higher than in untreated subjects. CONCLUSION: The high insulin response to
      glucose load seen in GH-treated subjects was appropriate to their glucose
      concentration and the insulin sensitivity index was unchanged relative to the
      pretreatment period. Increased insulin dosage in our patients did not induce an
      increase in leptin concentrations as had been hypothesised.

PMID- 11319660
TI  - BMI rebound, childhood height and obesity among adults: the Bogalusa Heart Study.
AB  - OBJECTIVE: The beginning of the post-infancy rise in the body mass index (BMI,
      kg/m2) has been termed the adiposity rebound, and several studies have found that
      an early rebound increases the risk for overweight in adulthood. We examined
      whether this relation is independent of childhood BMI levels. DESIGN: A
      longitudinal study of 105 subjects who examined at ages 5, 6, 7, 8 and 19-23 y.
      RESULTS: Subjects with an age at the BMI rebound (age(min)) of < or =5 y were, on
      average, 4-5 kg/m2 heavier in early adulthood than were subjects whose age(min)
      was > or =7 y. Age(min), however, was also correlated with childhood BMI levels
      (r approximately -0.5), and we found that age(min) provided no additional
      information on adult overweight if the BMI level at age 7 y (or 8 y) was known.
      In contrast, childhood height, which was also correlated with age(min) (r=-0.47),
      was independently related to adult BMI. Among relatively heavy (BMI=16.0 kg/m2) 5
      y-olds, a child with a height of 120 cm was estimated to be 1.2 kg/m2 heavier in
      adulthood than would a 104 cm tall child. CONCLUSIONS: Although an early BMI
      rebound was related to higher levels of relative weight in adulthood, this
      association was not independent of childhood BMI levels. The relation of
      childhood height to adult BMI needs to confirmed in other cohorts, but it is
      possible that childhood height may help identify children who are likely to
      become overweight adults.

PMID- 11319661
TI  - How does maturity adjustment influence the estimates of overweight prevalence in
      adolescents from different countries using an international reference?
AB  - OBJECTIVE: To investigate the effect of adjusting for differences in timing of
      maturation when assessing overweight prevalence among adolescents in different
      populations by using an international reference recommended by the WHO. DESIGN:
      Cross-sectional, comparative study in three large samples from China, Russia and
      the United States. SUBJECTS: A total of 2014 American, 1316 Chinese and 744
      Russian non-pregnant adolescent girls aged 10-18 y. MEASUREMENTS: Data on body
      weight, height, menarcheal status and age at menarche (AAM) were collected.
      Overweight was defined as age-sex-specific body mass index (BMI) greater than the
      85th percentiles from the US NHANES I data (collected in 1971-1974), which is
      recommended by the WHO for international use. Maturity adjustments were made
      using population differences in median age at menarche (MAM), calculated using
      the status quo method. MAM was 12.8 in the WHO reference population, 13.7 in
      China, 13.2 in Russia, and 12.6 in the US (NHANES III data). Maturation age
      matched BMI cut-offs were used to compute the adjusted prevalence. We also
      compared population-adjusted results with individually adjusted results in post
      menarcheal American girls (based on each girl's AAM) and in pre-menarcheal girls
      (based on breast stage). RESULTS: Maturity adjustment increased the estimated
      prevalence of overweight in China and Russia where girls mature later than the
      reference population, and decreased it in the NHANES III sample. The unadjusted
      and adjusted prevalence was 3.5 vs 4.9% in the China sample, 8.3 vs 9.7% in
      Russia, and 29.2 vs 28.0% in the US. The adjustment had a greater effect in
      younger adolescent girls (10-13 y) than in older girls (14-18 y). In general, we
      found a good agreement between the population and individual adjustments. Viewing
      the individual adjustment as a 'gold standard', the population method has a high
      sensitivity and specificity. CONCLUSION: This is the first study to assess WHO
      recommendations for maturation adjustment when estimating overweight prevalence
      in different countries. While the overall effects of adjustment are small,
      maturation status should be considered, particularly when assessing young
      adolescents, and populations with markedly different timing of maturation
      relative to the international reference. Population-based adjustment is useful
      and practical in situations where individual maturity data are not available.

PMID- 11319662
TI  - The role of dietary calcium and other nutrients in moderating body fat in
      preschool children.
AB  - OBJECTIVE: To assess preschool children's food consumption (24-60 months) and
      relate these findings to body composition at 70+/-2 months. DESIGN: A
      longitudinal study of children's dietary intakes for selected nutrients and
      servings of dairy products. SUBJECTS: Fifty-three white children participating in
      a longitudinal study (2-96 months) of children's food practices and growth.
      MEASUREMENTS: Using in-home interviews and trained interviewers, 18 days of
      dietary data and measured height and weight of each child at 6 month intervals
      were collected. Body composition was determined by dual energy X-ray
      absorptiometry. RESULTS: Dietary fat was 30-33% of energy with saturated and
      monounsaturated fat intakes>10% and polyunsaturated<10%. Adjusting for body mass
      index (BMI), GLM models to predict percent body fat (%BF) or grams of total fat
      (gTF) with mean longitudinal calcium intake (%BF: R2=0.51, F=7.88, P<0.0001; gTF:
      R2=0.51, F=9.84, P=0.0001) or total servings of dairy products (%BF: R2=0.47,
      F=6.93, P<0.0001; gTF: R2=0.47, F=8.31, P<0.0001) as independent variables gave
      significant results. Higher mean longitudinal calcium (mg/day) intakes and more
      servings/day of dairy products were associated with lower body fat. Males had
      significantly less body fat (P=0.01) than females. CONCLUSIONS: Higher
      longitudinal intakes of calcium, monounsaturated fat, and servings of dairy
      products were associated with lower body fat.

PMID- 11319663
TI  - How covert are covertly manipulated diets?
AB  - OBJECTIVE: To quantitatively assess subjects' ability to detect hedonic
      (palatability), sensory and nutritional differences between covertly manipulated
      high-fat (HF) and low-fat (LF) diets. SUBJECTS AND DIETS: This study examined the
      response of 16 subjects (eight men, eight women) to 20 LF and 20 HF versions of
      manipulated foods. Average percentage protein:fat:carbohydrate (by energy) and
      energy density (ED) of the two diets were 13:25:62, 371 kJ/100 g and 13:50:37,
      672 kJ/100 g, respectively. PROTOCOL: Subjects were asked to simultaneously
      assess the HF and LF versions of each food in terms of (i) subjective
      pleasantness of each food, (ii) perceived differences in appearance, smell, taste
      and texture of the foods, and (iii) for each sample to assess whether it was high
      or low in energy, protein, carbohydrate, fat, fibre, sugar and salt. ANALYSIS:
      Perceived pleasantness of HF and LF versions of the foods was compared by
      analysis of variance. Comparisons used chi-squared tests of independence to
      assess departure from the null hypothesis of no perceived difference in remaining
      parameters (ii-iii). RESULTS: On average, subjects exhibited no significant
      preference for LF or HF versions of the foods (no difference 15 foods, three HF
      foods more pleasant, two LF foods more pleasant (P<0.03)). On average there were
      no general differences in comparison of sensory attributes that were consistently
      ascribable to the LF or HF foods, although there were numerous significant
      differences for individual foods. Subjects appeared unable to distinguish the HF
      foods as being HF (66% of estimates) and guessed correctly 33% of the time. They
      were better able to categorize the LF foods correctly (53% correct). On aggregate
      43% of HF and LF foods were correctly identified. Subjects appeared able to
      detect sensory differences between foods but not to relate them to energy or
      nutrient content of these foods. CONCLUSIONS: These data suggest that subjects
      are on average not able to perceive large differences in the fat content of diets
      manipulated in this manner. In general the assumption that the manipulation of
      such foods is covert appears to hold, but subjects were far better at correctly
      identifying certain food types (dairy-based) over others.

PMID- 11319664
TI  - The relationship between restraint and weight and weight-related behaviors among
      individuals in a community weight gain prevention trial.
AB  - PURPOSE: The present study evaluated the cross-section and prospective
      associations between the Eating Inventory's (EI) total, flexible and rigid
      dietary restraint scales and changes in weight and behaviors in a community
      sample of adults enrolled in a 3 y weight gain prevention study. METHODS:
      Subjects were participants in the Pound of Prevention (POP) study, a community
      based weight gain prevention trial. RESULTS: Higher levels of baseline total,
      flexible and rigid dietary restraint were related to lower weight and more weight
      controlling behaviors at the baseline assessment. Baseline restraint measures
      positively predicted increases in weighing frequency over the 3 y follow-up.
      Increases in restraint over the follow-up period were related to decreases in
      weight, energy intake and television watching, and increases in self-weighing and
      physical activity. CONCLUSION: The EI's total, flexible and rigid restraint
      scales were not differently associated with weight and behaviors in this
      heterogeneous sample of adults who were attempting to lose weight. Developing
      methods to increase behavioral and cognitive strategies to control weight may
      help to prevent weight gain in clinical and community samples.

PMID- 11319665
TI  - Tumor necrosis factor-alpha--308 G/A polymorphism in obese Caucasians.
AB  - OBJECTIVE: Tumor necrosis factor-alpha (TNF-alpha) is expressed primarily in
      adipocytes, and elevated levels of this cytokine have been linked to obesity and
      insulin resistance. Recently, the A allele of a polymorphism in the 5'-flanking
      region of the TNF-alpha gene (G-308A) has been reported to be more frequent in
      obese than in lean subjects and has also been associated with increased
      expression of this cytokine in fat tissue and influences fat mass and insulin
      resistance. We, therefore, examined the relationship between this variant and
      obesity in a German Caucasian population. SUBJECTS AND METHODS: We genotyped 176
      index subjects recruited within the framework of the BErG (Berlin Ernahrung
      Geschwister)- Study for the TNF-alpha-G-308A polymorphism. Subjects were
      characterized for weight, height, waist and hip circumference, body mass index
      (BMI), body composition, glucose tolerance, leptin and angiotensinogen levels.
      RESULTS: The frequency of the -308A allele (0.18) was similar to that reported
      previously and genotype distribution was in Hardy-Weinberg equilibrium (GG,
      n=118; GA, n=53; AA, n=5). There was a significant difference in allele
      frequencies of the polymorphism by BMI quartiles (I,<27.3 kg/m2; II, 27.3-31.9
      kg/m2; III, 31.9-36.5 kg/m2; IV,>36.5 kg/m2, in each quartile n=44) with -308A
      allele carriers having a higher BMI than G allele carriers (P=0.013). Despite
      previous smaller studies that have related insulin resistance to the G-308A
      polymorphism, we found no relationship between glucose and insulin response
      during an oral glucose tolerance test (OGTT) and the polymorphism. Furthermore,
      none of the plasma parameters were related to the polymorphism. CONCLUSION: Our
      findings support the hypothesis that the G-308A polymophism of the TNF-alpha gene
      is associated with BMI. The G-308A polymorphism may, therefore, represent a
      genetic marker for increased susceptibility for obesity in Caucasians.

PMID- 11319666
TI  - Does obesity affect febrile responsiveness?
AB  - BACKGROUND AND OBJECTIVE: A decreased resistance to infection and impairments of
      immunity are common in obese humans and in rodents with hereditary obesity. Since
      brown fat thermogenesis is also suppressed in obese rodents, we hypothesized that
      obesity leads to a decreased febrile responsiveness. METHODS: We compared the
      fever responses to intravenous E. coli lipopolysaccharide (10 microg/kg) between
      Zucker fa/fa (obese due to a defective leptin receptor) and Fa/? (lean) rats and
      between Otsuka Long-Evans Tokushima Fatty (OLETF; obese due to the lacking
      cholecystokinin-A receptor) and Long-Evans Tokushima Otsuka (lean) rats. Obesity
      of Zucker fa/fa and OLETF rats was verified by increased body mass and fat
      content, hypertriglyceridemia and hypercholesterolemia. RESULTS: Neither fa/fa
      nor OLETF animals exhibited a decreased febrile responsiveness; if anything,
      their fevers tended to be higher than those in their lean counterparts.
      CONCLUSION: Obesity per se does not lead to antipyresis.

PMID- 11319667
TI  - Thinness and body shape of Playboy centerfolds from 1978 to 1998.
AB  - OBJECTIVE: Changes in the body weight and shape of Playboy centerfolds over the
      past two decades (1978-1998) were examined. METHODS: The body mass index (BMI)
      and waist-to-hip circumference ratio (WHR) were obtained from measurements
      reported by 240 centerfolds (ages 19-35 y). RESULTS: The 20-y averages (mean+/
      s.d.) were 18.1+/-0.8 kg/m2 for BMI and 0.68+/-0.03 for WHR, and there has been
      no appreciable change in either BMI or WHR in centerfolds over the past 20 y.
      Based on current recommendations for the classification of underweight (BMI<18.5
      kg/m2), 70% of the centerfolds were underweight. Further, 77.5% of the
      centerfolds were <85% of their ideal body weight. CONCLUSION: Given the
      perception of Playboy centerfolds as culturally 'ideal' women, the notion that
      70% of them are underweight highlights the social pressures on women to be thin
      and helps to explain the high levels of body dissatisfaction and disordered
      eating among women.

PMID- 11319668
TI  - The ECG and left ventricular hypertrophy in primary care hypertensives.

PMID- 11319669
TI  - Nitric oxide and hypertension: not just an endothelium derived relaxing factor!
AB  - The importance of endothelial nitric oxide (NO) generation in sustaining a tonic
      systemic vasodilatation is well established. Inhibiting NO production produces
      hypertension in animals and in humans and not surprisingly there has been
      considerable interest in establishing whether deficiencies of endothelial NO
      pathway activity are implicated in the aetiology of essential hypertension. The
      results of these investigations have been inconsistent with some suggestion that
      observed deficiencies of both basal and stimulated endothelial NO generation in
      hypertensive subjects may be an effect rather than the cause of raised arterial
      pressure. It is increasingly recognised that neuronal production of NO also
      influences cardiovascular homeostasis through its action as a neuromodulator
      within the autonomic nervous system. Overall NO has been shown to have sympatho
      inhibitory and vagotonic effects, acting by both central and peripheral
      mechanisms. Sympathetic overactivity, coupled with the permissive role of a
      depressed level of baroreflex mediated cardiac vagal control, may play a
      significant role in the genesis of human hypertension. Early work in hypertensive
      rats suggests that neuronal NO production is impaired at a number of key central
      sites concerned with autonomic cardiovascular regulation. This data is consistent
      with the pattern of autonomic dysfunction observed in human hypertension. The
      possibility that neuronal rather than endothelial production of NO might play a
      significant role in the aetiology of essential hypertension is a promising area
      for future human research.

PMID- 11319670
TI  - Urinary calcium excretion, sodium intake and blood pressure in a multi-ethnic
      population: results of the Wandsworth Heart and Stroke Study.
AB  - BACKGROUND: Hypertension is associated with increased urinary calcium excretion
      (UCa). A high sodium intake increases both UCa and blood pressure (BP). However,
      it is not clear whether these effects are modified by gender or ethnic origin.
      OBJECTIVES: To examine the relationships between BP, urinary sodium (UNa), gender
      and ethnic origin with both daily and fasting UCa in a population-based study.
      DESIGN AND METHODS: Out of 1577 individuals taking part in a cross-sectional
      survey, 743 were considered for the present analysis (407 women, 336 men) as they
      were all untreated, had provided a complete 24-h urine collection, and had all
      measurements of anthropometry, BP, UNa and UCa. They were 277 whites, 227 of
      black African origin and 239 South Asians. Comparisons were also carried out in
      the 690 participants who also provided 3-h fasting urine collections. RESULTS:
      After adjustment for confounders including age, and gender, 24-h UCa was
      significantly and independently associated with ethnic origin, BP and UNa. Mean
      24-h UCa was 4.62 (s.e. 0.11) mmol/d in whites, 3.33 (0.12) in South Asians and
      3.16 (0.13) in blacks (P < 0.001). a 100 mmol higher UNa predicted a 1.04 mmol
      higher daily UCa (P < 0.001), and a 20 mm Hg higher systolic BP predicted a 0.28
      mmol higher UCa. The slopes were not significantly different by ethnic group. The
      ethnic differences in UCa were present when fasting UCa was used instead (1.64
      [0.05] micromol/min in whites, 1.08 [0.06] in South Asians and 1.13 [0.06] in
      blacks; P < 0.001). CONCLUSIONS: These results indicate that BP, salt intake and
      ethnic origin are independent predictors of UCa in an unselected population.
      These relationships are unlikely to be the result of differences in Ca intake or
      intestinal Ca absorption as they are seen also after an overnight fast,
      suggesting that they may reflect differences in renal tubular handling. The
      estimated effects of either BP or sodium intake on UCa, sustained over many
      years, may be associated with significant effects on bone calcium content.

PMID- 11319671
TI  - Factors determining the 24-h blood pressure profile in normotensive patients with
      type 1 and type 2 diabetes.
AB  - Some controversy still exists about factors involved in the abnormal circadian
      pattern of blood pressure (BP) in diabetes, while prognostic value of non-dipping
      condition is being increasingly recognised. This study was aimed at evaluating
      the relative influence of autonomic neuropathy (AN) and albumin excretion on 24-h
      BP profile in type 1 and type 2 diabetes. We measured AN cardiovascular tests, 24
      h ambulatory BP, and urinary albumin excretion rate (UAE) in 47 type 1 and 34
      type 2 normotensive non-proteinuric diabetic patients. In type 1 diabetic
      patients day-night differences (Delta) in systolic and diastolic BP were lower in
      those with AN than in those without (3 +/- 9 vs 10 +/- 6%, P < 0.01, and 8 +/- 9
      vs 16 +/- 6%, P < 0.001), and in univariate regression analysis they were
      inversely related to both autonomic score, index of degree of AN (r = -0.61, P <
      0.001 and r = -0.65, P < 0.001), and to 24-h UAE (r = -0.39, P < 0.01 and r = 
      0.46, P < 0.001). In type 1 diabetic patients AN was also associated with lower
      nocturnal decrease in UAE (patients with AN vs without AN: -37 +/- 214 vs 49 +/-
      37%, P < 0.05), and with a stronger relationship between simultaneous 24-h UAE
      and 24-h BP (for systolic BP patients with AN vs without AN: r = 0.62, P < 0.01
      vs r = 0.28, NS). In type 2 diabetic patients Delta systolic BP was reduced in
      patients with AN compared to those without (4 +/- 7 vs 10 +/- 4%, P < 0.01), and
      it was related only to autonomic score (r = -0.42, P < 0.01). Using a stepwise
      regression analysis, in type 1 diabetic patients autonomic score was the variable
      of primary importance for Delta BP, while in type 2 diabetic patients it was the
      unique determinant not only of Delta systolic BP but also of 24-h systolic BP. In
      conclusion, AN is the pivotal factor of blunted nocturnal fall in BP in both type
      1 and type 2 diabetic patients. In type 1 diabetic patients AN is associated with
      attenuated circadian pattern of albuminuria and with a steeper relationship
      between albuminuria and BP, in type 2 diabetic patients AN is the only factor
      related to elevated 24-h BP levels. Longitudinal studies are needed to establish
      the potential role of autonomic dysfunction as a progression promoter for
      nephropathy and hypertension in type 1 and type 2 diabetes respectively.

PMID- 11319672
TI  - Have rapid socioeconomic changes influenced awareness of blood pressure in
      Poland?
AB  - The aim of our study was to evaluate changes in awareness of blood pressure
      during transition into a market economy in Poland. Thus, in 1994, we conducted a
      cross-sectional survey based on a questionnaire interview on a sample of 2080 men
      (M) and women (F) aged 18 years and over. The subjects were selected from a
      Polish population by stratified and cluster random sampling with quotas by the
      Center for Social Research in Sopot. They were asked if they were aware of blood
      pressure. The results were analysed according to age, sex, education level,
      income and place of living. In September 1997 we carried out the same
      investigation on a new group of 1664 adults. In addition to the questionnaire,
      the blood pressure (three recordings at home) measurements were completed. The
      interviewers were well-trained medical students. Awareness of blood pressure has
      declined (P < 0.001) from 71% in 1994 to 65.5% in 1997. The highest decrease in
      awareness of blood pressure was observed among less educated people, as well as
      among people living in smaller cities and villages. The overall prevalence of
      hypertension was 25.9% by 'older' WHO criteria (BP > or =160/95 mm Hg or taking
      antihypertensive medication) and 44.5% by JNC VI criteria (BP > or =140/90 mm Hg
      or taking antihypertensive medication). Forty-six percent of hypertensive
      subjects classified by JNC VI criteria were previously known to be hypertensives
      and 54% were newly detected (F: 39%, M: 69%). Low awareness of blood pressure in
      Poland is the crucial factor of insufficient detectability of hypertension.
      Decline of awareness of blood pressure being the most significant among people
      representing lower social status, emphasises the need for urgent preventive
      measures.

PMID- 11319673
TI  - Prevalence of left ventricular hypertrophy in Finnish primary health care
      hypertensive patients.
AB  - BACKGROUND: Hypertensive patients who present left ventricular hypertrophy (LVH)
      are at considerable risk of developing cardiovascular complications.
      Echocardiography, being the best method for assessing of LVH, is too expensive
      for routine daily practice particularly in primary health care. Therefore,
      electrocardiogram (ECG) still remains the most feasible method to assess LVH in
      these settings. OBJECTIVES: The aim of this study was to determine the prevalence
      of ECG-LVH in Finnish hypertensive primary health care patients and evaluate the
      quality of their blood pressure control. METHODS: A total of 255 general
      practitioners in 26 primary health care centres identified all of their
      hypertensive patients visiting during a 1-week period. A health examination was
      carried out on these patients by health nurses and laboratory tests, including
      ECG, were taken. The ECG's were analysed by using the Minnesota Code. Altogether,
      1746 hypertensive patients were examined. RESULTS: The prevalence of ECG-LVH when
      using Sokolow-Lyon criterion was 9.8% for males and 5.7% for females. The
      corresponding figures, when using the sex-specific Cornell product, were 14.9%
      for males and 18.8% for females. Only 17% of LVH patients had their blood
      pressure under good control (BP <140/90 mm Hg) as compared to 25% of non-LVH
      patients (P < 0.01). CONCLUSION: The prevalence of ECG-LVH in Finnish
      hypertensive primary health care patients is high. Despite this warning signal,
      the treatment situation for LVH patients was even worse than that of other
      hypertensives.

PMID- 11319674
TI  - Sphygmomanometer calibration: a survey of one inner-city primary care group.
AB  - Sphygmomanometers are the cornerstone of blood pressure management and yet there
      is no national standard for the regulation of this equipment in the UK. It is
      known that these machines may often be inaccurate, particularly those used in the
      community. We embarked upon a survey of all sphygmomanometers in current use in
      one inner city primary care group. Contrary to our initial hypothesis, inaccuracy
      rates were lower than in other reported community surveys with 2.3% of mercury
      and 14.8% of anaeroid sphygmomanometers failing the test. Surprisingly,
      inaccurate machines did not cluster in the less well developed practices. The
      implication is that all practices need to have procedures in place for the
      regular calibration of their sphygmomanometers.

PMID- 11319675
TI  - Breathing-control lowers blood pressure.
AB  - We hypothesise that routinely applied short sessions of slow and regular
      breathing can lower blood pressure (BP). Using a new technology BIM (Breathe with
      Interactive Music), hypertensive patients were guided towards slow and regular
      breathing. The present study evaluates the efficacy of the BIM in lowering BP. We
      studied 33 patients (23M/10F), aged 25-75 years, with uncontrolled BP. Patients
      were randomised into either active treatment with the BIM (n = 18) or a control
      treatment with a Walkman (n = 15). Treatment at home included either musically
      guided breathing exercises with the BIM or listening to quiet music played by a
      Walkman for 10 min daily for 8 weeks. BP and heart rate were measured both at the
      clinic and at home with an Omron IC BP monitor. Clinic BP levels were measured at
      baseline, and after 4 and 8 weeks of treatment. Home BP measurements were taken
      daily, morning and evening, throughout the study. The two groups were matched by
      initial BP, age, gender, body mass index and medication status. The BP change at
      the clinic was -7.5/-4.0 mm Hg in the active treatment group, vs -2.9/-1.5 mm Hg
      in the control group (P = 0.001 for systolic BP). Analysis of home-measured data
      showed an average BP change of -5.0/-2.7 mm Hg in the active treatment group and 
      1.2/+0.9 mm Hg in the control group. Ten out of 18 (56%) were defined as
      responders in the active treatment group but only two out of 14 (14%) in the
      control group (P = 0.02). Thus, breathing exercise guided by the BIM device for
      10 min daily is an effective non-pharmacological modality to reduce BP.

PMID- 11319676
TI  - Treating hypertension with a device that slows and regularises breathing: a
      randomised, double-blind controlled study.
AB  - OBJECTIVE: To examine the efficacy of a new device, which slows and regularises
      breathing, as a non-pharmacological treatment of hypertension and thus to
      evaluate the contribution of breathing modulation in the blood pressure (BP)
      reduction. DESIGN AND SETTING: Randomised, double-blind controlled study, carried
      out in three urban family practice clinics in Israel. PATIENTS: Sixty-five male
      and female hypertensives, either receiving antihypertensive drug therapy or
      unmedicated. Four patients dropped out at the beginning of the study.
      INTERVENTION: Self treatment at home, 10 minutes daily for 8 consecutive weeks,
      using either the device (n = 32), which guides the user towards slow and regular
      breathing using musical sound patterns, or a Walkman, with which patients
      listened to quiet music (n = 29). Medication was unchanged 2 months prior to and
      during the study period. MAIN OUTCOME MEASURES: Systolic BP, diastolic BP and
      mean arterial pressure (MAP) changes from baseline. RESULTS: BP reduction in the
      device group was significantly greater than a predetermined 'clinically
      meaningful threshold' of 10.0, 5.0 and 6.7 mm Hg for the systolic BP, diastolic
      BP and MAP respectively (P = 0.035, P = 0.0002 and P = 0.001). Treatment with the
      device reduced systolic BP, diastolic BP and MAP by 15.2, 10.0 and 11.7 mm Hg
      respectively, as compared to 11.3, 5.6 and 7.5 mm Hg (P = 0.14, P = 0.008, P =
      0.03) with the Walkman. Six months after treatment had stopped, diastolic BP
      reduction in the device group remained greater than the 'threshold' (P < 0.02)
      and also greater than in the walkman group (P = 0.001). CONCLUSIONS: The device
      was found to be efficacious in reducing high BP during 2 months of self-treatment
      by patients at home. Breathing pattern modification appears to be an important
      component in this reduction.

PMID- 11319677
TI  - Martorell's hypertensive leg ulcer: case report and concise review of the
      literature.
AB  - Hypertensive leg ulcers (Martorell's ulcers) are a unique form of lower extremity
      ischaemic leg ulcer. First described by Martorell, and Hines and Farber in the
      1940s, these ulcers are defined by pain disproportionate to the size of the
      ulcer, specific location on the lower extremity, female-to-male predominance,
      association with long-standing, often poorly, controlled hypertension, and
      healing response to specific antihypertensive agents. We present a case of
      Martorell's hypertensive ischaemic leg ulcer and a concise review of the 104
      previous cases in the world's English literature. Hypertensive ischaemic leg
      ulcers will be more commonly recognised with a renewed appreciation of the
      existence of this clinical entity.

PMID- 11319678
TI  - Reduced heat shock proteins: a mechanism to explain higher cardiovascular events
      associated with doxazosin.

PMID- 11319679
TI  - Experimental yellow fever virus infection in the Golden Hamster (Mesocricetus
      auratus). I. Virologic, biochemical, and immunologic studies.
AB  - This report describes the clinical laboratory findings in golden hamsters
      experimentally infected with yellow fever (YF) virus. An accompanying paper
      describes the pathologic findings. Following intraperitoneal inoculation of a
      virulent strain of YF virus, hamsters developed a high-titered viremia (up to
      109/mL) lasting 5--6 days and abnormal liver function tests. YF hemagglutination
      inhibiting antibodies appeared 4 or 5 days after infection, often while viremia
      was still present. The mortality rate in YF-infected hamsters was variable,
      depending on the virus strain and the age of the animals. Clinical and pathologic
      changes in the infected hamsters were very similar to those described in
      experimentally infected macaques and in fatal human cases of YF, which indicates
      that the golden hamster may be an excellent alternative animal model, in place of
      nonhuman primates, for research on the pathogenesis and treatment of YF and other
      viscerotropic flavivirus diseases.

PMID- 11319680
TI  - Experimental yellow fever virus infection in the Golden hamster (Mesocricetus
      auratus). II. Pathology.
AB  - Subadult and adult hamsters were inoculated intraperitoneally with 10(6) TCID(50)
      of yellow fever (YF) virus (Jimenez strain). Four animals from each group were
      subjected daily to histologic examination for 9 days. The liver showed spotty
      necrosis on day 3 after infection, which was followed by steatosis and focally
      confluent necrosis. In surviving hamsters, hepatocyte regeneration began on day
      8, which was accompanied by decreasing steatosis. The spleen initially exhibited
      lymphoid hyperplasia, which was followed by lymphoid depletion and increased
      phagocytosis by splenic macrophages. Focal pancreatic acinar necrosis and spotty
      adrenal cortical necrosis were seen transiently between days 5 and 7. Viral
      antigen was detected immunohistochemically in the liver and the spleen. TUNEL
      analysis showed a dynamic change of hepatocyte necrapoptosis, with activity
      corresponding to the severity of disease. The histopathologic changes were more
      severe in younger (subadult) animals. The YF-hamster model appears to be an
      accurate and inexpensive experimental system for studying the pathophysiology and
      treatment of YF.

PMID- 11319681
TI  - Patterns of plasma human immunodeficiency virus type 1 RNA response to
      antiretroviral therapy.
AB  - Early identification of treatment failure among human immunodeficiency virus
      (HIV) type 1--infected patients receiving antiretroviral therapy could enable
      clinicians to modify inadequate regimens and to improve treatment response.
      Clinical definitions of treatment failure, however, may not be ideally suited for
      this purpose. This study empirically characterizes the patterns of HIV-1 RNA
      response to antiretroviral therapy in patients in 4 AIDS clinical trials. The
      approach assumed 2 patterns of HIV-1 response: "on track," for eventual
      suppression to HIV-1 RNA levels below the limit of quantification, and "off
      track," for deviation from this response. The results of this on- or off-track
      classification generally agreed with the protocol-defined outcomes of virologic
      success and failure, thus validating these commonly used definitions. Overall,
      only a minority of patients went off track because of suboptimal HIV-1 RNA
      response by the first follow-up visit. Most patients who went off track did so at
      later time points and had sharp unexpected rebounds without prior indication of a
      suboptimal response.

PMID- 11319682
TI  - Treatment of primary human immunodeficiency virus type 1 infection with potent
      antiretroviral therapy reduces frequency of rapid progression to AIDS.
AB  - Immunologic data supporting immediate antiretroviral therapy in primary human
      immunodeficiency virus type 1 (HIV-1) infection are emerging; however, clinical
      benefit has not been demonstrated. The clinical and virologic course of 47
      patients who were enrolled from September 1993 through June 1996 and who were not
      initially treated with potent therapy was compared with the course of 20 patients
      who immediately began therapy with zidovudine, lamivudine, and indinavir.
      Demographic and baseline laboratory data were comparable. During 78 weeks of
      follow-up, the early-treatment cohort showed a reduced frequency of opportunistic
      infections (5% vs. 21.3%; relative risk, 0.11; P=.02), less frequent progression
      to AIDS (13% vs. 0%), and significantly less frequent nonopportunistic
      mucocutaneous disorders and respiratory infections (P<.01). Plasma HIV-1 RNA
      levels were <50 copies/mL in all patients who continued therapy; however, after 9
      -12 months, HIV-1 remained detectable in latently infected CD4(+) T cells and in
      lymph node mononuclear cells. Combination antiretroviral therapy during primary
      HIV-1 infection demonstrated a decreased frequency of minor opportunistic
      infections, mucocutaneous disorders, and respiratory infections and reduced
      progression to AIDS.

PMID- 11319683
TI  - Efficacy of low-dose intermittent subcutaneous interleukin (IL)--2 in antiviral
      drug--experienced human immunodeficiency virus--infected persons with detectable
      virus load: a controlled study of 3 il-2 regimens with antiviral drug therapy.
AB  - To evaluate the safety and efficacy of 3 regimens of intermittent subcutaneous
      (sc) interleukin (IL)--2 in a phase 2 study, 61 antiviral drug-experienced human
      immunodeficiency virus (HIV)--positive patients were randomly assigned to one of
      the following study arms: antiretroviral therapy (ART) plus IL-2 (12 million IU
      [MIU] by continuous intravenous infusion, followed by 7.5 MIU twice a day, sc,
      every 8 weeks); ART plus IL-2 (7.5 MIU twice a day, sc, every 8 weeks); ART plus
      IL-2 (3 MIU twice a day, sc, every 4 weeks); or ART alone. A significant increase
      of circulating CD4 cells was observed in IL-2--treated subjects, compared with
      those given ART alone. Low doses of IL-2 were better tolerated. Despite the
      incomplete suppression of viral replication, IL-2 with ART did not increase
      either plasma viremia or cell-associated HIV DNA levels. Low doses of
      intermittent sc IL-2 induced a stable increase of peripheral CD4 cells that was
      indistinguishable from those associated with higher, less well-tolerated doses of
      IL-2.

PMID- 11319684
TI  - A Phase 1 study of a recombinant viruslike particle vaccine against human
      papillomavirus type 11 in healthy adult volunteers.
AB  - Viruslike particles (VLPs) produced from the L1 protein of several
      papillomaviruses have induced protection from infection after live challenge in
      animal models. In the present study, the safety and immunogenicity of a human
      papillomavirus (HPV)--11 L1 VLP candidate vaccine were measured in a phase 1,
      dose-finding trial in humans. The vaccine was well tolerated and induced high
      levels of both binding and neutralizing antibodies. Marked increases in
      lymphoproliferation to HPV--11 L1 antigens were noted after the second
      vaccination. In addition, lymphoproliferation was induced after vaccination in
      peripheral blood mononuclear cells (PBMC) stimulated with heterologous L1 VLP
      antigens of HPV types 6 and 16. Statistically significant increases in HPV
      antigen--specific interferon--gamma and interleukin-5 production were measured
      from PBMC culture supernatants. This candidate HPV VLP vaccine induced robust B
      and T cell responses, and T cell helper epitopes appear to be conserved across
      HPV types.

PMID- 11319685
TI  - Characterization of the antibody response to pneumococcal glycoconjugates and the
      effect of heat-labile enterotoxin on IGg subclasses after intranasal
      immunization.
AB  - The antibody response to pneumococcal glycoconjugate (Pnc) was characterized by
      analyzing pneumococcal polysaccharide (PPS)-- and protein carrier-specific IgG
      subclass profiles and their relationship. Mice were immunized intranasally (inl)
      or subcutaneously (sc) with Pnc with mutants of Escherichia coli heat-labile
      enterotoxin, LT-R72 and LT-K63, as mucosal adjuvants. Subcutaneous immunization
      with Pnc alone induced predominantly IgG1, whereas native PPS administered sc
      induced very low IgG titers that were exclusively of the IgG3 subclass. Compared
      with sc immunization with Pnc alone, inl immunization with Pnc and LT mutants
      induced significantly higher systemic IgG2a, IgG3, and IgA antibodies to both PPS
      and the carrier, whereas the IgG1 titers were comparable. There also was a
      significant correlation between PPS- and protein carrier--specific antibody
      responses for all IgG subclasses. This demonstrates that LT mutants can be used
      to both enhance and modulate the antibody response to the PS moiety of
      glycoconjugate vaccines.

PMID- 11319686
TI  - Clones of Streptococcus pneumoniae isolated from nasopharyngeal carriage and
      invasive disease in young children in central Tennessee.
AB  - To determine whether nasopharyngeal carriage isolates of Streptococcus pneumoniae
      are of the same genetic background as isolates that caused invasive disease in
      one community, IS1167 and boxA genotypes were obtained for 182 pneumococcal
      isolates from children living in central Tennessee. The isolates represented 70
      combined IS1167-boxA genotypes. The genotypic diversity of the invasive isolates
      was significantly less than that of the total population (P=.003). Most of the
      carriage isolates belonged to genotypes unique to carriage, whereas most of the
      invasive isolates belonged to genotypes common to carriage and disease (P=.02).
      Monte Carlo simulations showed a greater number of genotypes unique to carriage
      than can be explained by chance (P<.05 in all cases). Two genotypes were
      identified by multilocus sequence typing as members of globally disseminated
      clones, and one such genotype that was strictly carriage in this sample caused
      disease in other studies. Thus, clones can have different propensities for
      carriage and invasion.

PMID- 11319687
TI  - Clonal relationships and extended virulence genotypes among Escherichia coli
      isolates from women with a first or recurrent episode of cystitis.
AB  - To identify bacterial predictors of recurrence and/or persistence in acute
      cystitis, extended virulence genotypes were compared with clonal background and
      epidemiologic status among 74 Escherichia coli urine isolates from women with
      first or recurrent episodes of urinary tract infection (UTI). Sequential isolates
      from patients with recurrent UTI were classified, using macrorestriction
      analysis, as having caused an isolated recurrence versus a single or multiple
      same-strain recurrences. papA, papG allele II, iha, and iutA predicted multiple
      same-strain recurrences, whereas nfaE and the absence of sfaS or fyuA predicted
      isolated recurrences. Phylogenetic group B2 accounted for 70% of isolates and for
      most of the putative virulence factors (VFs) studied. The meningitis-associated
      O18:K1:H7 clonal group comprised 18% of isolates, exhibited multiple VFs, and
      caused "once-only" recurrences less commonly than did other strains. These
      findings identify specific VFs and clonal groups against which preventive
      interventions might be beneficial and illustrate the importance of delineating
      pathogenetically relevant subgroups within the "recurrent cystitis" population.

PMID- 11319688
TI  - The relationships between ethnicity, sex, risk group, and virus load in human
      immunodeficiency virus type 1 antiretroviral-naive patients.
AB  - This cross-sectional study examined the relationships between ethnicity, sex,
      risk group, and virus load in human immunodeficiency virus type 1 (HIV-1)
      antiretroviral-naive patients. HIV-1 RNA levels were measured in 322 patients
      attending St. Thomas' Hospital between May 1997 and February 1999. By univariate
      analyses, only clinical status and CD4(+) cell count were related to virus load.
      In multivariate analysis, variables independently related to virus load were
      CD4(+) cell count (P=.001), being black African (P=.001), having a nonsexual risk
      for HIV infection (P=.03), and having AIDS (P=.05). Neither sex nor age was a
      significant predictor of initial virus load after adjusting for other variables.
      For a given CD4(+) cell count, black Africans and people who contracted HIV
      nonsexually presented with a virus load lower than that of patients in other
      groups. Because virus loads may need to be interpreted differently according to
      ethnicity, this may affect decisions on when to initiate antiretroviral therapy
      and how to interpret clinical trial results.

PMID- 11319689
TI  - Immunologic profile of human immunodeficiency virus-infected patients during
      viral remission and relapse on antiretroviral therapy.
AB  - A dissociation between plasma human immunodeficiency virus (HIV) RNA levels and
      CD4(+) cell counts has been reported in patients experiencing viral relapse while
      receiving antiretroviral therapy. This study compared patients with stable CD4(+)
      lymphocytes during viral relapse while receiving treatment with patients who had
      sustained virus suppression. Plasma HIV RNA levels, lymphocyte immunophenotyping,
      and T cell receptor excision circle (TREC) levels were measured. Naive CD4(+)
      lymphocyte phenotype and TREC levels were not significantly different in patients
      with virus suppression or in those who had relapsed. However, CD8(+) lymphocyte
      activation, including the number and percentage of activated cells and CD38
      antibody-binding capacity, was significantly elevated during viral relapse,
      compared with that in suppressed patients. By multivariable regression analyses,
      CD8(+) and CD4(+) lymphocyte activation were associated significantly with
      increasing plasma HIV RNA levels.

PMID- 11319690
TI  - Ampicillin-resistant Escherichia coli in gestational pyelonephritis: increased
      occurrence and association with the colonization factor Dr adhesin.
AB  - The pattern of ampicillin resistance and possible association with virulence
      factors of 78 Escherichia coli isolates taken from 78 pregnant women with
      pyelonephritis were evaluated. The current incidence of ampicillin resistance
      among pyelonephritis isolates (46%) was significantly higher than that reported
      in 1985 (22%). Resistance was found more frequently during the first (60%) and
      third (53%) trimesters than during the second trimester (33%). Of all dra(+) E.
      coli isolates, 75% were ampicillin resistant, whereas dra(+) isolates of O75
      serotype E. coli accounted for 87% of ampicillin-resistant strains. The
      significant increase of ampicillin resistance among gestational pyelonephritis E.
      coli and the association with the dra gene cluster encoding colonization and
      invasive capacity may warrant further study involving obstetric and neonate
      wards, with the latter being at the higher risk for potential problems.

PMID- 11319691
TI  - Plasmodium falciparum induces a Th1/Th2 disequilibrium, favoring the Th1-type
      pathway, in the human placenta.
AB  - During pregnancy, a local and systemic Th2 bias of maternal immunity favors Th1
      dependent infections such as malaria. This study measured cytokines secreted in
      cultures of chorionic villi, placental blood cells (PBC), and serum in term
      placentas from 88 malaria-infected and -noninfected Cameroon women. Interleukin
      (IL)--2 and --4 were consistently low; IL-1 beta, IL-6, granulocyte-macrophage
      colony-stimulating factor, and transforming growth factor (TGF)--beta 2 were
      highest in villi cultures. Tumor necrosis factor (TNF)--alpha, interferon (IFN)-
      gamma, and IL-10 were highest in PBC cultures. Malaria placental infection
      increased Th1-type cytokines, whereas Th2-type cytokines and TGF-beta 2 were
      unchanged. Addition of lipopolysaccharide or infected erythrocytes to cultures
      increased TNF-alpha, IL-1 beta, IL-6, and IL-10 secretions but not those of IFN
      gamma and IL-4. Overall, Plasmodium falciparum induced a placental immune
      response involving both Th1- and Th2-type cell activation. Although the Th1
      pathway was favored, IL-10 secretion was also increased, and this increase should
      be effective in protecting the placenta by controlling the negative effects of
      Th1 cytokines on pregnancy.

PMID- 11319692
TI  - High-level chloroquine resistance in Sudanese isolates of Plasmodium falciparum
      is associated with mutations in the chloroquine resistance transporter gene pfcrt
      and the multidrug resistance Gene pfmdr1.
AB  - Polymorphisms were examined in 2 Plasmodium falciparum genes, as were chloroquine
      responses of clones and isolates from a village in eastern Sudan. There was a
      significant association between an allele of the P. falciparum chloroquine
      resistance transporter gene (pfcrt-T76) and both in vitro and in vivo resistance.
      There was a less significant association with the multidrug resistance gene
      pfmdr1-Y86 allele. A significant association between pfmdr1-Y86 and pfcrt-T76 was
      apparent among resistant isolates, which suggests a joint action of the 2 genes
      in high-level chloroquine resistance.

PMID- 11319693
TI  - Once-daily regimen may increase drug holidays.

PMID- 11319695
TI  - Prenatal short-course zidovudine reduces mortality in children born to human
      immunodeficiency virus-positive mothers in rural Kenya.

PMID- 11319697
TI  - Chlamydia trachomatis omp1 genotyping.

PMID- 11319698
TI  - Sequence polymorphisms in pfcrt are strongly associated with chloroquine
      resistance in Plasmodium falciparum.

PMID- 11319700
TI  - Recruiting older adults in our studies.

PMID- 11319701
TI  - In their own words: oncology nurses respond to patient requests for assisted
      suicide and euthanasia.
AB  - Little is currently known about the context, nature, or frequency of nurses'
      responses to patient requests for help in dying. Only two empirical studies have
      surveyed American nurses about their actual responses to such requests. In one of
      those studies, 441 New England oncology nurses described how often patients ask
      them for help in ending their lives and also indicated how often they
      participated in assisted suicide and patient-requested euthanasia. One hundred
      and ten of those 441 nurses wrote comments on their returned questionnaires. This
      article describes the content analysis of those comments. Those oncology nurses
      who wrote have much to say about caring for patients at the end of life.

PMID- 11319702
TI  - Perceptions of health and their relationship to symptoms in African American
      women with type 2 diabetes.
AB  - Diabetes mellitus is an incurable disease and a major cause of mortality and
      morbidity. Diabetes disproportionately affects members of minorities who suffer
      from higher rates of complications and greater disability (Cowie & Eberhardt,
      1996). The purpose of this study was to (a) describe the symptoms of African
      American women with Type 2 diabetes and examine the relationship among diabetes
      related symptoms; (b) document complications of diabetes and perceptions of
      health and functioning; and (c) examine the relationship between duration of
      diabetes and age at diagnosis and perceived health. A convenience sample of 75
      African American women with Type 2 diabetes were interviewed. A 44-item
      questionnaire measured selected demographic variables, symptoms, documented
      complications, and their perceived relationship to diabetes. The SF-20 was used
      to measure perceptions of health status. Data show that African American women
      with Type 2 diabetes have a wide variety of symptoms and poor perceptions of
      their general health and physical functioning.

PMID- 11319703
TI  - Predictors of risk for adolescent childbearing.
AB  - The purpose of this research was to develop a predictive model that identifies
      young women at risk for adolescent motherhood. A stratified sample of 357
      adolescents was drawn from public health units and public schools in six randomly
      selected counties in North Central Florida. Data were collected regarding the
      environmental context (social and family), individual perceptions of self and
      trajectory, and adolescent motherhood status. A stepwise logistic regression was
      used to investigate the combined effects of these variables for identification of
      risk for adolescent motherhood. Using the combination of these variables,
      practitioners can identify adolescents at highest risk for early motherhood
      (97.66%) and those with the least risk of adolescent motherhood (approximately
      1%).

PMID- 11319704
TI  - Fatigue and hope: relationships to psychosocial adjustment in Korean women with
      breast cancer.
AB  - This study focuses on the relationships of fatigue and hope to psychosocial
      adjustment of 122 Korean women with breast cancer who received postsurgical
      chemotherapy or radiation therapy. The results indicated that after controlling
      for hope, fatigue uniquely accounted for 38% of the variance in psychosocial
      adjustment. After controlling for fatigue, hope uniquely accounted for 7% of the
      variance in psychosocial adjustment. However, there was no significant
      interaction between fatigue and hope in accounting for the variance in
      psychosocial adjustment. The findings inform clinicians of the importance of
      fatigue and hope, so that they may consider these factors when planning care for
      women with breast cancer, especially in women receiving chemotherapy or radiation
      therapy.

PMID- 11319705
TI  - Black populations, human immunodeficiency virus/acquired immune deficiency
      syndrome, and research: implications for nurses.
AB  - Knowledge that is generated from research is critical toward understanding the
      prevention, impact, and treatment of human immunodeficiency virus (HIV) disease
      and acquired immune deficiency syndrome (AIDS). During the past several decades,
      the Black community has been disproportionately affected by the HIV/AIDS
      epidemic. Therefore, engaging their participation in HIV/AIDS research is
      necessary to understand the disease further and to develop strategies for nursing
      interventions. Many factors hinder Blacks from participating in HIV/AIDS
      research. This review provides information for nurses about problems related to
      recruitment and recommendations for recruiting Black participants for HIV/AIDS
      research.

PMID- 11319706
TI  - Insights on the poster preparation and presentation process.
AB  - Dissemination of research findings and effective clinical innovations is key to
      the growth and development of the nursing profession. Several avenues exist for
      the dissemination of information. One forum for communication that has gained
      increased recognition over the past decade is the poster presentation. Poster
      presentations are often a significant part of regional, national, and
      international nursing conferences. Although posters are frequently used to
      disseminate information to the nursing community, little is reported about actual
      poster presenters' experiences with preparation and presentation of their
      posters. The purpose of this article is to present insights derived from
      information shared by poster presenters regarding the poster preparation and
      presentation process. Such insights derived from the personal experiences of
      poster presenters may assist others to efficiently and effectively prepare and
      present scholarly posters that disseminate information to the nursing community.

PMID- 11319707
TI  - Perceptions of human immunodeficiency virus and sexually transmitted disease risk
      among low-income adults: a pilot study.
AB  - Sexual risk-taking research and subsequent intervention programs have focused
      almost exclusively on adolescents and men who have sex with men. In comparison,
      less research has been conducted into adult heterosexual risk-taking behavior.
      The purposes of this pilot study were to test a survey instrument, assess how low
      income adults perceive their risk of human immunodeficiency virus (HIV) and
      sexually transmitted disease (STD) infection, and determine the degree to which
      condom use is a function of age. The Health Belief Model was used to guide the
      development of the survey instrument. In the Health Belief Model, age is a
      mediating factor that influences a person's likelihood to take action to change
      his or her lifestyle. Respondents perceived that their vulnerability to infection
      declined because of increased age and decreased frequency of coitus. Condom use
      was found to significantly decline as the age of the respondents increased.
      Although this is only a pilot study, the findings highlight the need for HIV and
      STD education for all age groups and genders.

PMID- 11319708
TI  - Dollars and sense: a primer for the novice in economic analyses (Part II).

PMID- 11319709
TI  - Lost in familiar places...again (on the nature of nursing leadership).

PMID- 11319710
TI  - Postprandial changes in sex hormones after meals of different composition.
AB  - The postprandial effects of different meals on serum testosterone, serum sex
      hormone-binding globulin (SHBG), and free androgen index were sequentially
      evaluated in 15 healthy men. The isocaloric meals contained different proteins
      and different quantities and type of fat as a mixed meal. Four test meals were
      given to subjects in random order: a lean meat meal, a tofu meal (both containing
      approximately 20% energy from fat), and meat meals with added animal fat or
      safflower oil (both 54% energy from fat). Blood samples were obtained at baseline
      and at 2, 3, and 6 hours after each meal. There was a significant decrease in
      testosterone and free androgen index after both tofu and lean meat meals. The 2
      hour serum testosterone and the decremental area under the curve were
      significantly more negative after the lean meat meal than the meat meal with
      added animal fat. The testosterone area under the curve was least for the high
      animal fat meal indicating little change from baseline. As men are postprandial
      for a significant proportion of the day, the lower sex hormone values after a low
      animal fat meal may provide long-term benefits in reducing the risk of diseases,
      such as prostate cancer, which appear to be sex hormone-dependent.

PMID- 11319711
TI  - Physiologic modeling of the intravenous glucose tolerance test in type 2
      diabetes: a new approach to the insulin compartment.
AB  - The minimal model of Bergman et al has been used to yield estimates of insulin
      sensitivity (Si) and glucose effectiveness (Sg) in type 2 diabetes by
      incorporating exogenous insulin protocols into the regular intravenous glucose
      tolerance test (IVGTT). These estimates, however, are influenced by the degree to
      which the dose of exogenous insulin is greater than the physiologic response to a
      glucose load. Moreover, most studies have related to type 2 diabetes subjects
      whose diabetes was relatively mild in terms of therapeutic requirements. To
      develop a "minimal disturbance" approach in estimating Si and Sg in type 2
      diabetes, we have used a reduced glucose load (200 mg/kg) and a "physiologic"
      insulin infusion throughout the IVGTT in a series of 8 patients, 5 of whom were
      insulin-requiring. Data from this approach were analyzed using the modelling
      program CONSAM to apply the Bergman model, either unmodified (BMM), or
      incorporating an additional delay element between the plasma and "remote" insulin
      compartments (MMD). Application of the MMD and extension of the IVGTT from 3 to 5
      hours improved successful resolution of Si and Sg from 37.5% (BMM, 3-hour IVGTT)
      to 100% (MMD, 5-hour IVGTT). Si was reduced in these type 2 diabetes patients
      compared with normal subjects (1.86 +/- 0.60 v. 8.65 +/- 2.27 min(-1) x microU(
      1) x mL x 10(4) P <.01). The results were validated in the type 2 diabetes group
      using a 2-stage euglycemic clamp ((Si)CLAMP = 2.02 +/- 0.42 min(-1) x microU(-1)
      x mL x 10(4) P >.4). Sg was not significantly reduced (2.00 +/- 0.25 type 2
      diabetes v. 1.55 +/- 0.26 normal min(-1) x 10(2)). Data from a group of normal
      nondiabetic subjects was then analyzed using the MMD, but this approach did not
      enhance the fit of the model compared with the BMM. This result indicates that
      the delay in insulin action in type 2 diabetes represents an abnormality whereby
      the onset of insulin action cannot be described as a single phase in the transfer
      of insulin from plasma to the remote compartment. It is postulated that the
      physiologic basis for this delayed action may relate to transcapillary
      endothelial transfer of insulin, this process limiting the rate of onset of
      insulin action.

PMID- 11319712
TI  - Effects of diets enriched with two different plant stanol ester mixtures on
      plasma ubiquinol-10 and fat-soluble antioxidant concentrations.
AB  - Plant stanols lower intestinal cholesterol absorption. This causes a decrease in
      serum low-density lipoprotein (LDL)-cholesterol, despite a compensatory increase
      in cholesterol synthesis. We therefore hypothesized that plant stanols also
      change LDL-cholesterol-standardized concentrations of ubiquinol-10 (a side
      product of the cholesterol synthesis cascade) and of those fat-soluble
      antioxidants that are mainly carried by LDL. To examine this, 112
      nonhypercholesterolemic subjects consumed low erucic acid rapeseed oil (LEAR)
      based margarine and shortening for 4 weeks. For the next 8 weeks, 42 subjects
      consumed the same products, while the other subjects received products with
      vegetable oil-based stanols (2.6 g sitostanol plus 1.2 g campestanol daily, n =
      36) or wood-based stanols (3.7 g sitostanol plus 0.3 g campestanol daily, n =
      34). Consumption of both plant stanol ester mixtures increased cholesterol
      synthesis and lowered cholesterol absorption, as indicated by increased serum
      cholesterol-standardized lathosterol and decreased plant sterol concentrations,
      respectively. Compared with the control group, absolute plasma ubiquinol-10
      concentrations were lowered by 12.3% +/- 18.9% (-0.14 microg/mL v. the control
      group; P =.004; 95% confidence interval [CI] for the difference in changes, -0.05
      to -0.22 microg/mL) in the vegetable oil-based group and by 15.4% +/- 13.0% (
      0.17 microg/mL v. the control group; P <.001; 95% CI for the difference, -0.08 to
      -0.27 microg/mL) in the wood-based group. Changes in LDL-cholesterol-standardized
      ubiquinol-10 concentrations were not significantly changed. The most lipophylic
      antioxidants, the hydrocarbon carotenoids (beta-carotene, alpha-carotene, and
      lycopene), decreased most, followed by the less lipophylic oxygenated carotenoids
      (lutein/zeaxanthin and beta-cryptoxanthin) and the tocopherols. These reductions
      were related to the reduction in LDL, which carry most of these antioxidants. The
      decrease in the hydrocarbon carotenoids, however, was also significantly
      associated with a decrease in cholesterol absorption. LDL-cholesterol
      standardized antioxidant concentrations were not changed, except for beta
      carotene, which was still, although not significantly, lowered by about 10%. We
      conclude that the increase in endogenous cholesterol synthesis during plant
      stanol ester consumption does not result in increased LDL-cholesterol
      standardized concentrations of ubiquinol-10, a side product of the cholesterol
      synthesis cascade. Furthermore, decreases in absolute fat-soluble antioxidant
      concentrations are related to decreases in LDL-cholesterol. However, for the most
      lipophylic carotenoids, some of the reduction was also related to the decrease in
      cholesterol absorption.

PMID- 11319713
TI  - Thyroid hormone increases plasma cholesteryl ester transfer protein activity and
      plasma high-density lipoprotein removal rate in transgenic mice.
AB  - Thyroid dysfunction produces multiple alterations in plasma lipoprotein levels,
      including high-density lipoprotein (HDL). Cholesteryl ester transfer protein
      (CETP) and hepatic lipase (HL) are important proteins that modulate the
      metabolism of HDL. Thus, the effect of thyroid hormone on the activities of CETP
      and of HL was investigated using hypothyroid and hyperthyroid CETP transgenic
      (Tg) and nontransgenic (nTg) mice. Hyperthyroid Tg mice plasma lipoprotein (LP)
      profile analysis showed a significant increase in the very-low-density
      lipoprotein (VLDL) fraction (P <.001) and decrease in the HDL fraction (P <.005),
      whereas in the hypothyroid Tg mice an increase in low-density lipoprotein (LDL)
      was observed (P <.02). CETP activity was measured as the transfer of (14)C
      cholesteryl ester (CE) from labeled HDL to LDL by an isotopic assay indicative of
      mass. Hyperthyroid Tg mice had twice as much plasma CETP activity as compared
      with their controls, while in hypothyroid Tg mice plasma CETP activity did not
      change. The role of CETP in determining the changes in LP profile of hyperthyroid
      animals was confirmed by showing that nTg wild-type hyperthyroid and euthyroid
      mice exhibited the same percent cholesterol distribution in LP. Postheparin HL
      activity measured in hyperthyroid Tg mice was significantly reduced (P <.05).
      (3)H-cholesteryl oleoyl ether ((3)H-Cet)-HDL plasma fractional removal rate (FRR)
      was approximately 2-fold faster in the hyperthyroid Tg mice than in controls, but
      was not modified in hypothyroid animals. Tissue uptake of (3)H-Cet was examined
      in 10 tissue samples: levels were significantly increased in skeletal muscle and
      decreased in small intestine in hyperthyroid Tg mice, and decreased in the small
      intestine of hypothyroid Tg mice. In conclusion, the excess of thyroid hormone
      accelerates HDL metabolism in CETP transgenic mice mainly due to an increase in
      plasma CETP activity and independently from the HL activity. Hypothyroid status
      did not change CETP activity and HDL metabolism.

PMID- 11319714
TI  - Alterations in body composition and fat distribution in growth hormone-deficient
      prepubertal children during growth hormone therapy.
AB  - Growth hormone (GH) deficiency in children results in increased body fat, reduced
      fat-free mass (FFM) including muscle (protein) and bone, and abdominal obesity.
      Thus, proper GH secretion likely has major developmental influences on later
      health risks including cardiovascular diseases and osteoporosis. However, the in
      vivo control of the development of the body composition and fat distribution by
      GH has not yet been accurately investigated using children with GH deficiency as
      a model. We determined the effect of GH therapy (GH replacement, n = 3; GH +
      physiologic cortisol and thyroxine replacement, n = 3) on body composition, the
      proportional composition of the FFM, and body fat distribution in GH-deficient
      prepubertal children compared with healthy control children (n = 6) not treated
      with GH. The GH-deficient and control children were initially matched for gender,
      bone age, and weight. As assessed by a 4-compartment model, GH therapy reduced
      percent body fat during the first 3 months of therapy but not thereafter. This
      change was primarily due to FFM, which increased 3-fold more in the GH-deficient
      group and accounted for 91.5% of the increase in body weight. Fat mass increased
      in the controls but was unchanged in the GH-deficient group. Therapy temporarily
      increased the proportional contribution of water to the FFM, decreased the
      proportion of mineral, and slightly increased the proportion of protein. Using
      magnetic resonance imaging (MRI), abdominal visceral fat was reduced in the GH
      deficient group and unchanged in the controls. Abdominal subcutaneous fat
      measured in the same image was not changed. The abdominal and suprailiac skinfold
      thicknesses also were not decreased in the GH-deficient group. In conclusion,
      within 1 to 3 months, GH therapy accelerates lean tissue accrual, especially the
      water and protein components, but has a smaller effect on reducing fat mass. GH
      therapy has site-specific effects on reducing abdominal adiposity.

PMID- 11319715
TI  - Acute suppressive effect of hydrocortisone on p47 subunit of nicotinamide adenine
      dinucleotide phosphate oxidase.
AB  - We have recently demonstrated that reactive oxygen species (ROS) generation by
      polymorphonuclear leukocytes (PMNL) and mononuclear cells (MNC) is inhibited
      following the intravenous administration of hydrocortisone. This is associated
      with a parallel decrease in intranuclear NFkappaB, known to modulate inflammatory
      responses including ROS generation. We have also shown that the plasma levels of
      interleukin-10 (IL-10), an anti-inflammatory and immunosuppressive cytokine
      produced by TH2 cells, are also increased after hydrocortisone administration. In
      this study, we have investigated the effect of hydrocortisone on p47(phox)
      subunit, a key component of nicotinamide adenine dinucleotide phosphate (NADPH)
      oxidase, in MNC and the pharmacodynamics of this effect with ROS generation and
      plasma IL-10 levels. p47(phox) subunit protein levels in MNC showed a progressive
      decrease after hydrocortisone administration. It reached a nadir at 4 hours and
      increased thereafter to a baseline level at 24 hours. ROS generation also
      decreased, reached a nadir between 2 and 4 hours, and returned to a baseline
      level at 24 hours. IL-10 concentrations increased, peaked at 4 hours, and
      reverted to the baseline levels at 24 hours. In conclusion, p47(phox) subunit
      suppression may contribute to the inhibition of ROS generation in MNC after
      hydrocortisone administration. This suppression occurs in parallel with the
      suppression of NFkappaB and an increase in IL-10 plasma levels. Therefore, it
      would appear that the decrease in intranuclear NFkappaB and an increase in IL-10
      may cause the inhibitory modulation on p47(phox) subunit and ROS generation by
      MNC following hydrocortisone and other glucocorticoids.

PMID- 11319716
TI  - Increased protein kinase C theta in skeletal muscle of diabetic patients.
AB  - In this study we have investigated whether protein kinase C (PKC) protein and
      activity are increased in skeletal muscle of human diabetic patients. The protein
      content of different PKC isoforms (beta, Theta, epsilon, delta, mu, and zeta) in
      the particulate fraction was measured, using Western analysis, in human rectus
      abdominus skeletal muscle from obese (hyperinsulinemic, normoglycemic) and obese
      diabetic (hyperinsulinemic, hyperglycemic) subjects. PKC Theta protein content
      was significantly higher in the particulate fraction of muscle from diabetic
      patients compared with the nondiabetic controls. PKC Theta was immunoprecipitated
      and its activity was measured in muscle from diabetic and nondiabetic controls.
      There was a significant increase in PKC Theta activity in muscle from diabetic
      patients compared with muscle from nondiabetic controls. Therefore, both PKC
      Theta protein content and activity were significantly increased in the
      particulate fraction in muscle from diabetic patients, suggesting the involvement
      of this isoform in diabetes. Most of the PKC Theta protein was found in the
      cytosol. There was no change in cytosolic PKC Theta protein content in muscle
      from diabetic patients compared with muscle from nondiabetic controls. Thus, the
      increase in particulate-associated PKC Theta was likely due to translocation and
      activation rather than an increase in protein mass.

PMID- 11319717
TI  - Aspirin reduces blood cholesterol in copper-deficient rats: a potential
      antioxidant agent?
AB  - The purpose of this study was to examine whether the hypocholesterolemic effect
      of aspirin is to due to its antioxidant properties. Oxidative stress was induced
      in rats by feeding them a copper-deficient diet. Copper deficiency reduced the
      activity of the enzyme superoxide dismutase (SOD) and lowered liver copper
      concentration but elevated liver iron. The combination of reduced SOD activity,
      high liver iron, and low liver copper resulted in an oxidative stress assessed by
      increased liver lipid peroxidation compared with copper-adequate controls. In
      addition, copper-deficient rats exhibited elevation of blood cholesterol. The
      administration of aspirin lowered both liver lipid peroxidation and blood
      cholesterol. It is suggested that the hypocholesterolemic properties of aspirin
      could be due to its ability to reduce oxidative stress.

PMID- 11319718
TI  - Effects of maternal iron restriction in the rat on blood pressure, glucose
      tolerance, and serum lipids in the 3-month-old offspring.
AB  - Epidemiologic studies have demonstrated associations between low birth weight and
      increased rates of adult diseases such as hypertension and diabetes. Maternal
      iron restriction in the rat has been reported to both reduce birth weight and to
      elevate blood pressure at 40 days of age. The aim of the present study was to
      extend these findings to investigate the effects of maternal iron restriction on
      glucose tolerance and serum lipids, 2 important components of the metabolic
      syndrome, in adult offspring. Blood pressure, glucose tolerance, and serum lipids
      were measured in the 3-month-old offspring of iron-restricted dams. Rats were
      placed on control or iron-restricted diets 1 week before mating. At term, dams on
      the iron-restricted diet were anemic with decreased haemoglobin, red blood cell
      (RBC) count, hematocrit, and mean RBC volume compared with controls. Neonates
      from iron-restricted litters were more severely anemic than the dams. At birth,
      body weight was lower in the offspring of iron-restricted dams than in controls
      and was still decreased at 3 months of age. At this same age, systolic blood
      pressure was significantly elevated in the offspring of iron-restricted dams.
      Glucose tolerance was improved in the maternal iron-restricted group. Fasting
      serum insulin levels were not different between the control and maternal iron
      restricted groups. Fasting serum triglyceride was decreased in the offspring of
      iron-restricted dams compared with controls. Fasting serum cholesterol and free
      fatty acid concentrations were similar in both groups. These results suggest that
      maternal iron restriction has long-term effects on physiology and metabolism in
      the offspring. Some of these findings are comparable to those reported for the
      maternal protein-restriction model. It is thus speculated that the long-term
      effects of maternal dietary restriction may result from common fetal metabolic
      responses to this restriction.

PMID- 11319719
TI  - Changes in skin blood flow in type 2 diabetes induced by prostacyclin:
      association with ankle brachial index and plasma thrombomodulin levels.
AB  - In a previous study, we reported that beraprost sodium (BPS), a stable
      prostaglandin I(2) (PGI(2)) analog, increases skin blood flow in the feet of both
      control subjects and patients with type 2 diabetes, and that the flow increase
      induced by BPS is lower in diabetic patients than in controls. The present study
      was undertaken to clarify factors associated with smaller increases in skin blood
      flow in the feet of patients with type 2 diabetes after the administration of
      BPS, and to investigate the relationship between microalbuminuria and the changes
      in skin blood flow induced by the PGI(2) analog. We studied 61 patients with type
      2 diabetes: 10 received placebo (control) and 51 (31 with normoalbuminuria and 20
      with microalbuminuria) received BPS. Using laser Doppler flowmetry, we measured
      the skin blood flow at the pulp of the right big toe before and 90 minutes after
      administration of 40 microg BPS, and calculated the change in blood flow, i.e.,
      delta flux (peak flux at 90 minutes - basal flux at 0 minutes). Plasma
      concentrations of soluble thrombomodulin (TM) were determined using an enzyme
      immunoassay (EIA) sandwich method. BPS significantly increased skin blood flow in
      the treatment group compared with the placebo group (P <.01). The delta flux was
      positively correlated with the value of the ankle brachial index (ABI) (r =.41, P
      <.0038) and was negatively correlated with plasma TM levels (r = -.53, P <.0001).
      By multiple regression analysis both the ABI value and the plasma TM level
      retained a significant influence on delta flux. Furthermore, both the delta flux
      and the ABI value in patients with microalbuminuria were lower than in patients
      with normoalbuminuria (P <.05). The results suggest that BPS increases the skin
      blood flow of the toe of patients with type 2 diabetes and that the increased
      flow is independently influenced by the value of the ABI and the plasma TM
      levels; in addition, microalbuminuria is associated with the impairment of
      vasodilation in the feet in response to BPS.

PMID- 11319720
TI  - Insulin sensitivity of blood glucose versus insulin sensitivity of blood free
      fatty acids in normal, obese, and obese-diabetic subjects.
AB  - We calculated insulin sensitivity indices (ISI) concerning the insulin effect on
      both glycemia and blood free fatty acids (FFA), named ISI(gly) and ISI(ffa),
      respectively, in 34 normal, 27 obese, and 11 obese-diabetic subjects by using the
      following formulas: ISI(gly)= 2/[(INSp x GLYp) +1], and ISI(ffa)= 2/[(INSp x
      FFAp)+1], in which INSp, GLYp, and FFAp = insulinemic, glycemic, and FFA areas
      during oral glucose tolerance test (OGTT) (75 g glucose, suggested sampling time:
      0, 1, and 2 hours) of the person studied. A slight modification of these formulas
      allows the calculation of insulin resistance indices (IRI), ie, IRI(gly) and
      IRI(ffa). ISI and IRI are complementary, as their sum is always equal to 2, so
      that IRI can be deduced from ISI and vice versa. By using basal levels instead of
      areas, insulin sensitivity (or resistance) in the basal state can also be
      measured. Basal levels and areas are expressed by taking the mean normal value as
      1, so that in normal subjects ISI(gly) and ISI(ffa), as well as IRI(gly) and
      IRI(ffa), are always around 1, with maximal variations comprised between 0 and 2.
      ISI(ffa) was markedly reduced in both the obese (mean, 0.47 +/- 0.04) and the
      obese-diabetic (mean, 0.41 +/- 0.06) subjects, whereas ISI(gly) was less reduced
      in the obese (mean, 0.57 +/- 0.04) than in the obese-diabetic (mean, 0.40 +/-
      0.03) subjects. ISI(gly)-basal was less affected than ISI(ffa)-basal in both
      groups. Multiple regression showed that ISI(gly) and ISI(ffa) were significantly
      inversely correlated with age, body mass index (BMI), and diastolic (but not
      systolic) blood pressure. Meta-analysis of data from the literature showed that
      ISI(gly) was significantly correlated with the hyperinsulinemic-euglycemic clamp
      data. However, the "clamp" is performed under artificial, persistent
      hyperinsulinemia (which entails FFA suppression) as never occurs in the life of
      patients, whereas our indices are performed under physiologic conditions, and
      represent simple tools suitable for clinical or epidemiologic studies, allowing
      assessment of whole-body insulin sensitivity with regard to both glycemia and
      blood FFA.

PMID- 11319721
TI  - Insulinotropic actions of exendin-4 and glucagon-like peptide-1 in vivo and in
      vitro.
AB  - This study compares in vitro effects of exendin-4 and glucagon-like peptide (GLP)
      1 on basal and glucose-stimulated insulin release from isolated rat islets and in
      vivo insulinotropic actions of exendin-4 and GLP-1 after an intravenous glucose
      challenge in rats. In static incubation of isolated islets, changing ambient
      glucose concentration from 3 mmol/L to 10 mmol/L stimulated insulin secretion 9.8
      +/- 1.3-fold. The addition of exendin-4 or GLP-1 (1 nmol/L to 1 micromol/L)
      increased glucose-stimulated insulin secretion up to 5.8 +/- 1.6-fold and 3.3 +/-
      1.0-fold, respectively, over basal rates (defined as no hormones added, 3 mmol/L
      glucose) and 19.6 +/- 2.3-fold and 15.0 +/- 3.1-fold at 10 mmol/L glucose. In
      dynamically perfused isolated islets exposed to 7.5 mmol/L glucose, insulin
      secretion increased 6.4 +/- 1.5-fold, and exendin-4 (20 nmol/L) or GLP-1 (20
      nmol/L) increased this similarly by up to 13.5 +/- 2.8 and 12.7 +/- 3.9
      fold,respectively. Anesthetized rats administered 5.7 mmol/kg intravenous glucose
      increased plasma insulin concentration 3.0-fold. Infusion of exendin-4 or GLP-1
      increased this to a maximum of 7.6-fold and 5.3-fold, respectively. As with
      isolated islet studies, in vivo dose responses and concentration responses with
      exendin-4 and GLP-1 were bell-shaped. When insulinotropic effects were mapped
      onto the steady-state plasma concentrations associated with these infusion rates,
      both peptides exhibited bell-shaped concentration responses with peak
      insulinotropic effects occurring with plasma peptide concentrations of
      approximately 1 nmol/L in this model. In summary, exendin-4 and GLP-1 exhibited
      similar insulinotropic potencies (median effective dose [ED(50)]) when assessed
      on a concentration basis in in vitro and in vivo models, while exendin-4
      exhibited greater efficacy (maximum response).

PMID- 11319722
TI  - Insulin secretory dysfunction and insulin resistance in the pathogenesis of
      korean type 2 diabetes mellitus.
AB  - Although insulin resistance has been shown to be a primary defect causing type 2
      (non insulin-dependent) diabetes mellitus in Pima Indians and Caucasians, insulin
      secretory defect has also been known to be an important factor in the development
      of type 2 diabetes. We undertook a study to investigate the initial abnormality
      of glucose intolerance in Koreans. A total of 370 Korean subjects were classified
      into 5 groups according to their degree of glucose intolerance (normal fasting
      glucose [NFG]/normal glucose tolerance [NGT], n = 95; impaired fasting glucose
      [IFG]/NGT, n = 29; NFG/impaired glucose tolerance [IGT], n = 60; IFG/IGT, n = 68;
      diabetes, n = 118). Insulinogenic index was used as an index of early-phase
      insulin secretion. Insulin resistance was assessed by the R value of the
      homeostasis model assessment [HOMA(R)]. Insulinogenic index significantly
      decreased in subjects with IFG/NGT and NFG/IGT compared with those with NFG/NGT.
      However, there was no significant difference in HOMA(R) between subjects with
      NFG/NGT and those with IFG/NGT or NFG/IGT. Insulinogenic index decreased
      significantly with the increase of plasma glucose 120-minute value at the earlier
      stage of glucose intolerance compared with HOMA(R). These results suggest that
      early-phase insulin secretory defect may be the initial abnormality in the
      development of type 2 diabetes in Korean subjects.

PMID- 11319723
TI  - Insulin resistance, dietary cholesterol, and cholesterol concentration in
      postmenopausal women.
AB  - Questions remain concerning the effect of variations in cholesterol intake on
      plasma cholesterol concentration, as well as on the role of factors modulating
      the metabolic impact of this dietary intervention. To define the impact of wide
      variations in dietary cholesterol intake on plasma total and low-density
      lipoprotein (LDL) cholesterol concentrations, as well as testing the hypothesis
      that resistance to insulin-mediated glucose disposal would accentuate the
      increase in plasma total and LDL cholesterol concentrations in response to a
      given increment in dietary cholesterol intake, we performed a prospective,
      randomized study comparing diets varying in cholesterol content in 65 healthy,
      postmenopausal women, 31 defined as insulin-resistant and 34 as insulin
      sensitive. The changes in total and LDL cholesterol in response to increments in
      dietary cholesterol of up to approximately 800 mg/day were modest in magnitude,
      without evidence of a statistically significant diet-induced increase in
      cholesterol concentration, or of any difference in the responses of insulin
      resistant as compared with insulin-sensitive women. These results indicate that
      relatively large increments in dietary cholesterol intake had little effect on
      total or LDL cholesterol concentrations in healthy, postmenopausal women,
      irrespective of whether they were insulin-resistant or insulin-sensitive.

PMID- 11319725
TI  - Exercise increases hexokinase II mRNA, but not activity in obesity and type 2
      diabetes.
AB  - Glucose phosphorylation, catalyzed by hexokinase, is the first committed step in
      glucose uptake in skeletal muscle. Hexokinase II (HKII) is the isoform that is
      present in muscle and is regulated by insulin and muscle contraction. Glucose
      phosphorylation and HKII expression are both reduced in obese and type 2 diabetic
      subjects. A single bout of exercise increases HKII mRNA and activity in muscle
      from healthy subjects. The present study was performed to determine if a moderate
      exercise increases HKII mRNA expression and activity in patients with type 2
      diabetes. Muscle biopsies were performed before and 3 hours after a single bout
      of cycle ergometer exercise in obese and type 2 diabetic patients. HKII mRNA and
      activity and glycogen synthase activity were determined in the muscle biopsies.
      Exercise increased HKII mRNA in obese and diabetic subjects by 1.67 +/- 0.34 and
      1.87 +/- 0.26-fold, respectively (P <.05 for both). Exercise did not
      significantly increase HKI mRNA. When HKII mRNA increases were compared with the
      2.26 +/- 0.36-fold increase in HKII mRNA previously reported for healthy lean
      subjects, no statistically significant differences were found. In contrast to the
      increase in HKII activity observed after exercise by lean healthy controls,
      exercise did not increase HKII activity in obese nondiabetic or diabetic
      subjects. Exercise increased glycogen synthase activity (GS(0.1) and GS(FV))
      significantly in both obese nondiabetic and type 2 diabetic patients. The present
      results indicate that there is a posttranscriptional defect in the response of
      HKII expression to exercise in obese and type 2 diabetic subjects. This defect
      may contribute to reduced HKII activity and glucose uptake in these patients.

PMID- 11319724
TI  - Contribution of net hepatic glycogen synthesis to disposal of an oral glucose
      load in humans.
AB  - The contribution of hepatic glycogen synthesis to whole body glucose disposal
      after an oral glucose load was examined using (13)C nuclear magnetic resonance
      (NMR) spectroscopy to measure liver glycogen content in healthy, volunteers after
      an overnight fast. In group 1 (n = 14), hepatic glycogen synthesis was measured
      using (13)C-NMR spectroscopy for 240 minutes after ingestion of 98 +/- 1 g
      glucose. Liver volumes were measured using magnetic resonance imaging (MRI). To
      assess the direct (glucose --> glucose-6-P --> glucose-1-P --> uridine
      diphosphate (UDP)-glucose --> glycogen) and indirect (3-carbon units --> -->
      glycogen) pathways of liver glycogen synthesis, group 2 (n = 6) was studied with
      an identical glucose load enriched with [1-(13)C]glucose along with acetaminophen
      to noninvasively assess the (13)C enrichment in hepatic UDP-glucose. The fasting
      hepatic glycogen content was 305 +/- 17 mmol/L liver, and the liver volume was
      1.46 +/- 0.07 L. For the initial 180 minutes after ingestion of glucose, hepatic
      glycogen concentrations increased linearly (r =.94, P =.0006) achieving a maximum
      concentration of 390 +/- 7 mmol/L liver and then remained constant until the end
      of the study. The mean maximum rate of net hepatic glycogen synthesis was 0.48 +/
      0.07 mmol/L liver-minute. Total liver glycogen synthesis could account for 16.7
      +/- 3.8 g (17% +/- 4%) of the glucose ingested, and of this, 10.5 +/- 2.4 g (63%
      +/- 7%) was synthesized by the direct pathway. In conclusion, after ingestion of
      98 g of glucose: (1) 16.7 +/- 3.8 g (17% +/- 4%) glucose was stored in the liver
      as glycogen, and (2) 63% +/- 7% (10.5 +/- 2.4 g) of this glycogen was formed via
      the direct pathway.

PMID- 11319726
TI  - Vascular insulin/insulin-like growth factor-1 resistance in female obese Zucker
      rats.
AB  - Because insulin resistance/diabetes may cause inordinate vascular complications
      in females, we have investigated the effects of insulin and insulin-like growth
      factor (IGF-1) on vascular reactivity in 12-week-old female Zucker obese (Ob)
      rats, a rodent model of insulin resistance and its lean (Ln) age-matched
      counterpart. Endothelium intact aortic rings from Ob animals and their Ln
      littermates (12 weeks of age) were subjected to contractile concentration
      responses to phenylephrine (PE) followed by relaxation to isoproterenol (Iso),
      with and without preincubation for 2 hours with cholera toxin (CTX; 1 microg/mL)
      or pertussis toxin (PTX; 2 microg/mL) and before and after incubation with either
      insulin or IGF-1 (100 nmol/L) for 1 hour. Systolic blood pressure was higher (138
      +/- 3 v. 109 +/- 4 mm Hg; P <.0001) in the 12-week-old Ob rats. Contractile
      responses to PE were similar in both groups; however, both insulin and IGF-1
      induced a paradoxical increase (P <.001) in contraction in Ob vasculature (929 +/
      92 v. 679 +/- 25 mg, respectively). CTX alone decreased contraction in the Ob (P
      <.02) and PTX in the Ln (P <.02), but there were no interactions between either
      IGF-1 or insulin and the toxins. Marked impairment of relaxation to Iso was seen
      in aortic rings of these female Ob rats (ED(50) = 2.6 micromol/L v. 418 nmol/L, P
      =.0002), an effect exacerbated by preincubation with either insulin or IGF-1 (P
      =.0001). Again, no role for G-proteins could be demonstrated. Insulin-dependent
      glucose uptake was severely impaired (P <.05) in aortic segments of the Ob
      insulin-resistant rats. Insulin receptor binding, tyrosine kinase activity (TKA),
      and abundance of several G-protein alpha subunits (inhibitory and stimulatory) in
      solubilized arterial membrane preparations (assessed by Western blot) were
      comparable in the 2 groups. These results indicate that resistance to the
      vascular actions of insulin/IGF-1 in female Ob rats is a postreceptor event that
      parallels glucose uptake resistance and is independent of G-proteins.

PMID- 11319727
TI  - Effects of free fatty acids on beta-cell functions: a possible involvement of
      peroxisome proliferator-activated receptors alpha or pancreatic/duodenal
      homeobox.
AB  - It is well known that acute administration of fatty acids enhances insulin
      release from beta cells, although chronic exposure to fatty acids inhibits
      insulin release (lipotoxicity). The mechanism for these reciprocal effects of
      fatty acids on insulin release remains to be elucidated. The present study was
      performed to investigate the effects of fatty acids on gene expression related to
      glucose metabolism or insulin biosynthesis. In islets cultured with palmitate for
      8 hours, glucose-induced insulin release was enhanced together with increment of
      pyruvate carboxylase (PC) mRNA or peroxisome proliferator-activated receptors
      (PPAR)alpha. In contrast, by extending the culture period up to 48 hours, glucose
      induced insulin release or islet insulin content was significantly impaired by
      the coexistence of palmitate. Concomitantly, PC, PPARalpha, GLUT-2, glucokinase
      (GK), preproinsulin, or pancreatic/duodenal homeobox-1 (PDX-1) mRNA were
      significantly suppressed in those islets cultured for 48 hours with palmitate.
      These data may imply that during short-term culture period palmitate promotes
      PPARalpha gene expression, which enhances PC mRNA expression leading to the
      enhancement of insulin release, whereas during long-term culture period,
      palmitate rather inhibits PPARalpha mRNA, which reduces PC mRNA expression.
      Furthermore, palmitate reduces GLUT-2, GK, or preproinsulin mRNA expression
      probably through the inhibition of PDX-1 mRNA.

PMID- 11319728
TI  - Selective breeding for infant vocal response: a role for postnatal maternal
      effects?
AB  - N:NIH rats were selectively bred on the basis of high or low rates of ultrasonic
      vocalization (USV) response to isolation at 10 days of age (Brunelli et al.,
      1997: Dev Psychobiol 31:255-265). To examine the possibility of postnatal
      maternal effects in the generational transmission of divergent traits, pups were
      cross-fostered shortly after birth between dams of the two lines (Low- and High
      USV). Controls were fostered to dams of the same line (in-fostered). Additional
      (population) control data were obtained from the entire 13th generation of the
      selectively bred lines. USV rates of cross-fostered pups in each line were not
      significantly different from rates of in-fostered pups of the same line. High USV
      line pups cross-fostered to Low USV line dams weighed significantly less than in
      fostered pups, on the day of testing. The results provide no evidence for a
      postnatal maternal contribution to the USV phenotype. Prenatal and/or perinatal
      maternal effects have not been ruled out.

PMID- 11319729
TI  - Variation in reproductive traits is associated with short anogenital distance in
      female rats.
AB  - Anogenital distance was used as a biomarker for natural variation in prenatal
      androgenization of female rats and was associated with individual differences in
      a suite of reproductive characteristics. Females with short anogenital distances
      were likely to have first vaginal estrus earlier than females with longer
      anogenital distances and to have first vaginal estrus on the same day as vaginal
      opening. In young adulthood, females with short anogenital distances had shorter
      ovarian cycles and less intense lordosis reflexes in response to manual palpation
      than those with longer anogenital distances, but only when living individually,
      not in groups. Taken together, these findings indicate that prenatal
      androgenization affects reproductive traits throughout the life span.

PMID- 11319730
TI  - Comparison of the effects of early handling and early deprivation on maternal
      care in the rat.
AB  - It has been reported in the rat that postnatal manipulations can induce robust
      and persistent effects on offspring neurobiology and behavior, mediated in part
      via effects on maternal care. There have, however, been few studies of the
      effects of postnatal manipulations on maternal care. Here, we describe and
      compare the effects on maternal behavior on postnatal days 1-12 of two
      manipulations, early handling (EH, 15-min isolation per day) and early
      deprivation (ED, 4-hr isolation per day), relative to our normal postnatal
      husbandry procedure. Maternal behavior was measured at five time points across
      the dark phase of the reversed L:D cycle. EH yielded an increase in arched-back
      nursing across several time points but did not affect any other behavior. ED
      stimulated a bout of maternal behavior such that licking and arched-back nursing
      were increased at the time of dam-litter reunion, although not at any other time
      point. Neither EH nor ED affected weaning weight significantly. Importantly,
      within-treatment variation was high relative to these between-treatment effects.

PMID- 11319731
TI  - Human fetal and neonatal movement patterns: Gender differences and fetal-to
      neonatal continuity.
AB  - Longitudinal quantification of leg movements per minute for human subjects during
      both fetal and neonatal periods was accomplished from videotapings conducted
      antenatally (ultrasonography 30, 34, and 37 weeks gestational age) and
      postnatally (birth and 6 weeks of age). Fetal/neonatal subjects displayed
      decreasing numbers of leg movements per minute during antenatal development (30
      to 37 weeks), followed by increasing numbers of leg movements per minute during
      postnatal development (birth to 6 weeks of age). Male subjects displayed greater
      numbers of leg movements per minute than female subjects during both antenatal
      and postnatal development. Fetal-to-neonatal continuity for numbers of leg
      movements per minute was found for comparisons between fetal (37 weeks
      gestational age) and neonatal (during sleep states at birth) measures, and
      females displayed a stronger and different movement continuity pattern than
      males. These results indicate a differential time course for neurobehavioral
      development of male and female fetuses/neonates, and the findings have
      implications for the clinical assessment of fetal neurobehavioral development and
      well-being.

PMID- 11319732
TI  - Attachment and sleep: a study of night waking in 12-month-old infants.
AB  - Sleep regulation was examined from a mother-child relational perspective.
      Although the link between sleep and attachment has been previously discussed,
      empirical support is rather limited. This report, which is a part of a
      longitudinal investigation of sleep in infancy, examines the association between
      the child's sleep pattern and mother-infant attachment in 94 mother-infant dyads.
      At 12 months each dyad participated in the Strange Situation procedure; 77% were
      securely attached. Mothers' description of the infant's fussiness was not found
      to predict the attachment pattern, but was associated with the sleep habits. It
      was found that 55% of the secure and 60% of the ambivalent children were
      described as night wakers. To a sub-group of 37 infants, a sleep monitor
      (actigraph) was provided for two nights' recordings. The frequency of the
      objective awakenings was higher than what mothers reported but similar for the
      secure and insecure infants. The findings confirm that night waking at the end of
      the first year is a common developmental phenomenon. Among this group of non-risk
      infants, sleep characteristics were only marginally associated with the quality
      of the child's attachment relationship.

PMID- 11319734
TI  - Dimensional changes of dental impression materials by thermal changes.
AB  - Dental impression materials for prosthodontic treatment must be easy to use,
      precisely replicate of oral tissue, be dimensionally stable, and be compatible
      with gypsum materials. The dimensional accuracy of all materials is affected by
      thermal changes; impression materials shrink during cooling from mouth
      temperature (37 degrees C) to room temperature (23 degrees C). Five kinds of
      light body addition-reaction silicone impression materials [Contrast (CT), Voco
      Co., Germany; Examix (EM), GC Co., Japan; Extrude (EX), Kerr Co., USA; Imprint II
      (IM), 3M Co., USA; Perfect (PF), Handae Chemical, Korea] were tested by making
      cylindrical specimens (6 mm diameter and 12 mm height). The thermal expansion of
      the impression materials was measured with a thermomechanical analyzer (TMA 2940,
      TA Instruments, USA) between 23-37 degrees C. Data were analyzed via the Mann
      Whitney Usage Test. To simulate actual dental impressions, tooth and tray shapes
      were modeled to measure the linear shrinkage of impression materials at anterior
      and posterior locations. The thermal expansion of impression materials tested
      decreased as follows: CT >or= PF >or= EM >or= EX >or= IM (p < 0.05). The anterior
      region changed more than the posterior region for the same impression materials.
      The dimensional changes averaged more than 40 microm in the anterior region, but
      less than 40 microm in the posterior region for all materials. Thermal expansion
      coefficients of some impression materials were significantly different from each
      other (p < 0.05), and the anterior region had more dimensional change than the
      posterior region for the same impression materials.

PMID- 11319735
TI  - Vascular graft healing. II. FTIR analysis of polyester graft samples from
      implanted bi-grafts.
AB  - FTIR-ATR analysis has shown that the 4-step process for preclotting polyester
      vascular grafts results in a uniform and reproducible fibrin coating of the
      polyester fibers. Western blot analyses have shown that FN and VEGF are also
      present in this fibrin coating. FTIR-ATR analyses of explanted grafts indicate
      that, while the in vivo healing of these preclotted polyester grafts proceed
      through the inflammation, proliferation, and remodeling phases of normal wound
      healing, these phases are modified. Because the fibrin coating provides a
      nonporous barrier between peri-graft tissue and the flowing blood, these
      molecular changes are controlled by the interactions of blood-borne constituents
      with the lumenal surface of the preclotted graft. Also, a well prepared
      preclotted polyester graft shows a minimal inflammatory response. After
      implantation, the fibrin preclot is more than 90% gone by the fifth day. However,
      the proliferation phase, involving synthesis of new protein and polysaccharide
      materials to replace the fibrin, appears to have begun by the third day.
      Detection of collagen I in the 5-day explants suggests that the overlapping
      remodeling phase of healing has begun. Protein and saccharide materials continue
      to be synthesized and remodeled, and, by the tenth day, collagen IV is detected.
      By 14-days post-implantation, there is an increase in collagen IV and cellular
      membrane lipids. Because collagen IV is an indicator of the presence of
      endothelial cells, some of these cellular membranes must be of endothelial
      origin. Thus, it appears that FTIR-ATR can be a useful tool in the study of
      vascular healing.

PMID- 11319736
TI  - Effect of hydroxyapatite sintering temperature on intracellular ionic
      concentrations of monocytes: a TEM-cryo-X-ray microanalysis study.
AB  - Hydroxyapatite used as bone replacement can lead to particle release in the
      implantation site. These particles interact with monocytes, which are the first
      immune cells to colonize the implant and an inflammatory site. Thanks to cryo-X
      ray microanalysis, we can observe cells in a state close to the physiological one
      and we have access to diffusible ions. We paid particular attention to the
      potassium-to-sodium ratio, which is one of the best viability criteria. We used
      this method to study the interaction between three hydroxyapatite particles
      treated at three different temperatures (not treated, treated at 600 degrees C
      and 1180 degrees C), and monocytes. In the culture condition, the hydroxyapatite
      treated at 1180 degrees C underwent the least dissolution. We demonstrate that
      monocytes were altered by the three hydroxyapatite particles. The hydroxyapatite
      particules treated at 600 degrees C were found to be more toxic.

PMID- 11319737
TI  - Lifetime predictions for resin-based composites using cyclic and dynamic fatigue.
AB  - Because dental restorative materials undergo fatigue in use, testing is often
      performed in the laboratory to evaluate material responses to cyclic loading. The
      purpose of this study was to compare the lifetime predictions resulting from two
      methods of fatigue testing: dynamic and cyclic fatigue. Model composites were
      made in which one variable was the presence of a silanizing agent, and specimens
      tested in 4-point flexure. Cyclic fatigue was carried out at a frequency of 5 Hz,
      while dynamic fatigue testing spanned seven decades of stress rate application.
      Data were reduced and the crack propagation parameters for each material were
      calculated from both sets of fatigue data. These parameters were then used to
      calculate an equivalent static tensile stress for a 5-year survival time. The 5
      year survival stresses predicted by dynamic fatigue data were approximately twice
      those predicted by cyclic fatigue data. In the absence of filler particle
      silanization, the survival stress was reduced by half. Aging in a water-ethanol
      solution reduced the survival stresses by a factor of four to five. Cyclic
      fatigue is a more conservative means of predicting lifetimes of resin-based
      composites.

PMID- 11319738
TI  - A new bioresorbable polymer for screw augmentation in the osteosynthesis of
      osteoporotic cancellous bone: a biomechanical evaluation.
AB  - The aim of the study was to assess the mechanical efficacy of a new resorbable
      polymer developed on the basis of alkylene bis(dilactoyl)-methacrylate to improve
      the anchorage of osteosynthesis material in cancellous bone. Cancellous bone
      screws were inserted in bovine as well as in human vertebrae and human femoral
      condyles and were augmented with the new polymer or polymethylmethacrylate
      (PMMA), respectively. Nonaugmented screws were used as controls. A removal torque
      test, a dynamic fatigue test, and a pullout test were performed. Augmentation
      with the new polymer increased the removal torque by 84% in human femoral bone.
      In the dynamic fatigue test of bovine vertebrae, the removal torque after cyclic
      loading was 115% higher for the new polymer compared to the nonaugmented
      controls. In the human vertebrae, the reinforcement with the new polymer
      increased the removal torque after dynamic loading by 114%. The augmentation with
      the new polymer increased the pullout force by 88% in bovine vertebrae and by
      118% in human vertebrae in comparison to nonaugmented screws. It was concluded
      that augmentation by the new resorbable polymer significantly enhanced the
      anchorage of bone screws in cancellous bone. The mechanical efficiency of the new
      polymer was comparable to that of PMMA cement.

PMID- 11319739
TI  - In vivo model for frontal sinus and calvarial bone defect obliteration with
      bioactive glass S53P4 and hydroxyapatite.
AB  - An in vivo model was developed to investigate the usability of a frontal sinus
      and a calvarial bone defect obliteration with bioactive glass S53P4 (BG) and
      hydroxyapatite (HA) granules. Roofs of 21 Elco rabbit frontal sinuses were
      drilled open from 4 separate holes using a standard method, and the sinuses,
      located in pairs, in frontal bone were filled with BG on one side and with HA on
      the other side. Two parallel posterior defects were covered with a pedicled
      periosteum flap, and 2 anterior defects with a free flap. The stability of
      materials, new bone, and connective tissue formation were observed with
      histomorphometry, scanning electron microscopy (SEM), energy dispersive X-ray
      analysis (EDXA), and X-ray pictures at 1, 3, 6, and 12 months postoperatively.
      The results showed more rapid resorption of filling material (p = 0.019) and new
      bone formation (p = 0.0001) in the defects filled with BG than in the
      corresponding HA-filled defects studied by histomorphometry throughout the study.
      New bone formation and resorption of materials were faster in defects covered by
      a pedicled flap than by a free periosteum flap. The results were supported by SEM
      histomorphometric and radiologic analysis. Both bioactive materials studied were
      well tolerated in frontal sinuses and in calvarial bone defects. The experimental
      model showed the influence of early periosteum vascularization on accurate
      frontal sinus filling and the healing process in rabbit frontal sinuses.

PMID- 11319740
TI  - Bone induction by porous glass ceramic made from Bioglass (45S5).
AB  - Porous glass ceramic, which was prepared from Bioglass powder (45S5, U.S.
      Biomaterials) by foaming with diluted H(2)O(2) solution and sintering at 1000
      degrees C for 2 h, was implanted as cylinders (5 mm in diameter and 6 mm in
      length) in thigh muscles of dogs for 3 months. Histological observation was made
      on thin un-decalcified sections. Bone formation was histologically found in pores
      of all implants (X16) retrieved from 16 dogs. The bone tissue was also identified
      with backscattered scanning electron microscopy observation (BSE) and energy
      dispersive X-ray microanalysis (EDX). This is the first report of bone induction
      in soft tissues of animals by glass ceramic that has long been recognized as a
      bioactive (osteoconductive) biomaterial. The present results justify the impetus
      to investigate the osteoinductivity of calcium phosphate-based biomaterials, to
      study the mechanism of bone induction (osteoinduction) by calcium phosphate-based
      biomaterials, to develop osteoinductive calcium phosphate-based biomaterials, and
      to examine the relation between osteoinduction and osteoconduction.

PMID- 11319741
TI  - Long-term measurement of bone strain in vivo: the rat tibia.
AB  - Despite the importance of strain in regulating bone metabolism, knowledge of
      strains induced in bone in vivo during normal activities is limited to short-term
      studies. Biodegeneration of the bond between gauge and bone is the principle
      cause of this limitation. To overcome the problem of bond degeneration, a unique
      calcium phosphate ceramic (CPC) coating has been developed that permits long-term
      attachment of microminiature strain gauges to bone. Using this technique, we
      report the first long-term measurements of bone strain in the rat tibia. Gauges,
      mounted on the tibia, achieved peak or near peak bonding at 7 weeks. Measurements
      were made between 7-10 weeks. Using ambulation on a treadmill, the pattern and
      magnitude of strain measured in the tibia remained relatively constant between 7
      10 weeks post implantation. That strain levels were similar at 7 and 10 weeks
      suggests that gauge bonding is stable. These data demonstrate that CPC-coated
      strain gauges can be used to accurately measure bone strain for extended periods,
      and provide an in vivo assessment of tibial strain levels during normal
      ambulation in the rat.

PMID- 11319742
TI  - The effect of contact area on wear in relation to fixed bearing and mobile
      bearing knee replacements.
AB  - It is generally assumed that the wear rates in knee replacements are reduced as
      the contact area is increased. Hence, fixed bearing or mobile bearing designs
      with large contact areas throughout the full range of flexion wear less than
      partially conforming fixed-bearing designs. This hypothesis was investigated in
      an experimental model, where flat-ended ultra high molecular weight polyethylene
      pins of varying diameters were reciprocated and rotated on polished metal plates
      under a constant load with serum lubrication. The pin diameters ranged from 8-23
      mm, giving nominal contact pressures from 23.9-2.8 MPa, covering the range
      associated with a wide spectrum of total knees including mobile-bearings. For pin
      diameters of 8-12 mm, the mean wear rates were in the range of 5.0-16.0 E-10
      g/cycle. For diameters of 17 and 23 mm, the mean wear rates were approximately
      1.0 E-10 g/cycle. The latter wear rates were significantly less than the former.
      Scanning electron microscopy indicated milder wear processes with the larger
      diameters, while the smaller diameters exhibited transverse ripples and cracks
      and detachment of thin layers from the surface. The percentages of granules
      (mostly submicron), fibrils and flakes, and the sizes of these particle types
      were similar among all pin diameters, except that, for the 23 mm pin diameter,
      the percentage of fibrils increased and of flakes decreased. This work supports
      the hypothesis that larger contact areas, up to the maximum area tested in our
      study, produce lower wear rates, and suggests that there is no disadvantage
      regarding particle type or size associated with the larger areas of contact.

PMID- 11319743
TI  - A simple synthetic route to the formation of a block copolymer of poly(lactic-co
      glycolic acid) and polylysine for the fabrication of functionalized, degradable
      structures for biomedical applications.
AB  - This article documents the formation of a block copolymer of poly(lactic-co
      glycolic acid) and polylysine via a simple coupling technique using dicyclohexyl
      carbodiimide (DCC). The resulting polymer has been characterized via UV-Vis
      spectroscopy, GPC, (1)H NMR, and elemental analysis, is soluble in a wide variety
      of solvents, and is easily processable, making the technique a simple and
      practical one for the formation of functionalized, degradable block copolymers
      for the fabrication of functionalized structures for biomedical applications.

PMID- 11319744
TI  - A novel amorphous calcium phosphate polymer ceramic for bone repair: I. Synthesis
      and characterization.
AB  - Traditional materials for bone repair or replacements such as autografts and
      allografts have a limited supply and other complications. Thus, alternative
      materials need to be explored. Three-dimensional, porous composites prepared from
      bioresorbable polymers and hydroxyapatite or other calcium phosphate ceramics are
      promising materials for the repair or replacement of diseased or damaged bone.
      However, in many cases the ceramic component of these composites is crystalline
      in nature, while bone apatite is made of a poorly crystalline, carbonated
      phosphate system. In this study, we synthesized a noncrystalline, carbonated
      calcium phosphate ceramic by carrying out the reaction within bioresorbable PLAGA
      microspheres using a modified emulsion/solvent evaporation technique, making each
      individual microsphere a composite. Sintering the composite microspheres together
      yielded a bioresorbable, porous, 3-dimensional scaffold that may be ideal for
      tissue ingrowth, making this composite scaffold potentially suitable for bone
      repair applications.

PMID- 11319745
TI  - Biodegradation of polyether polyurethane inner insulation in bipolar pacemaker
      leads.
AB  - Several bipolar coaxial pacemaker leads, composed of an outer silicone rubber
      insulation and an inner polyether polyurethane (PEU) insulation, which were
      explanted due to clinical evidence of electrical dysfunction, were analyzed in
      this study. Optical microscopy (OM) and scanning electron microscopy (SEM) were
      used to determine the cause of failure. Attenuated total reflectance-Fourier
      transform infrared microscopy (ATR-FTIR) was used to analyze the PEU insulation
      for chemical degradation. In all leads, the silicone rubber outer insulation
      showed no signs of physical damage. Physical damage to the inner PEU insulation
      was the source of electrical dysfunction. Cracks through the PEU compromised the
      insulation between the inner and outer conductor coils in the lead. It was
      observed with SEM that these cracks originated on the outer surface of the inner
      insulation and progressed inward. ATR-FTIR analysis showed that the PEU had
      chemically degraded via oxidation of the ether soft segment. Furthermore, it was
      revealed that chemical degradation was more advanced on the outer surface of the
      PEU. It was hypothesized that hydrogen peroxide permeated through the outer
      silicone insulation and decomposed into hydroxyl radicals that caused the
      chemical degradation of PEU. The metal in the outer conductor coil catalyzed the
      decomposition of the hydrogen peroxide. Chemical degradation of the PEU could
      also have been catalyzed by metal ions created from the corrosion of the metal in
      the outer conductor coil by hydrogen peroxide. Physical damage probably occurred
      in regions of the leads that were subjected to a higher hydrogen peroxide
      concentration from inflammatory cells and high degrees and rates of strain due to
      intercorporeal movement, including, but not limited to, cardiac movement.
      Chemical degradation and physical damage probably had a synergistic affect on
      failure of the insulation, in that as chemical degradation proceeded, the polymer
      surface became brittle and more susceptible to physical damage. As physical
      damage proceeded, cracks propagated into the unaffected bulk, exposing it to
      oxidants.

PMID- 11319746
TI  - Treatment of suture line bleeding with a novel synthetic surgical sealant in a
      canine iliac PTFE graft model.
AB  - CoSeal mark surgical sealant (CoSeal) was evaluated for inhibiting suture line
      bleeding using a canine iliac PTFE graft model. Both iliac arteries of 12
      heparinized canines were grafted with PTFE. CoSeal was applied to the suture
      lines of one graft in each animal. The contra-lateral graft served as a control
      and bleeding was controlled with gauze and pressure (tamponade). The cross-clamps
      were removed 30 s following application of CoSeal. Times to hemostasis and volume
      of blood loss at each graft site were determined. Compared to tamponade control,
      CoSeal significantly reduced the time to hemostasis (average of 5 min vs. greater
      than 15 min, p < 0.05) and blood loss (19 g vs. 284 g, p < 0.05). Small amounts
      of CoSeal were visible grossly or histologically at day 7. Histology showed
      moderate to marked inflammation in CoSeal sites and moderate inflammation in
      control sites at day 7. At 30 and 60 days, no CoSeal was visible grossly or
      histologically. Histology showed moderate inflammation in both CoSeal treated
      sites and in control sites at day 30 and mild to moderate inflammation in both
      CoSeal and control sites at day 60. CoSeal significantly reduced the time to
      hemostasis and blood loss in comparison to tamponade.

PMID- 11319747
TI  - Long- and short-term effects of biological hydrogels on capsule microvascular
      density around implants in rats.
AB  - Fibrous capsule formation around implants can inhibit solute exchange between
      implantable devices and the circulation. Parylene-n coated polycarbonate disks
      surrounded with growth factor reduced Matrigel (MG) or several gelatin-based
      matrices were implanted intramuscularly into rats for 21 or 50 days. MG
      supplemented with vascular endothelial growth factor (VEGF) or basic fibroblast
      growth factor (bFGF) increased capsule microvascular density at 21 days (p <
      0.05) when compared to bare parylene-coated polycarbonate disks (control). The
      increased microvascular density around VEGF- and bFGF-treated implants regressed
      by 50 days and was no longer significantly different from controls. The
      microvascular density induced by the gelatin-based matrices was not significantly
      different from controls at 21 days, but was increased at 50 days (p < 0.05),
      suggesting a slower, long-term effect. Disks treated with MG and gelatin-based
      matrices had thinner capsules at 21 days (p < 0.05). By 50 days, the capsule
      thicknesses around these implants were no longer statistically thinner than
      controls. The capsule thickness around implants treated with VEGF, bFGF, and
      essential gelatin-based matrix was thinner than controls at 50 days (p < 0.05).
      These results indicate that it is possible to increase functional microvascular
      density within fibrous capsules using angiogenic growth factors and gelatin-based
      matrices. However, this effect may be short-lived, requiring chronic
      administration of growth factors.

PMID- 11319748
TI  - In vitro and in vivo investigations into the biocompatibility of diamond-like
      carbon (DLC) coatings for orthopedic applications.
AB  - Diamond-like carbon (DLC) shows great promise as a durable, wear- and corrosion
      resistant coating for biomedical implants. The effects of DLC coatings on the
      musculoskeletal system have not been investigated in detail. In this study, DLC
      coatings were deposited on polystyrene 24-well tissue culture plates by fast-atom
      bombardment from a hexane precursor. Two osteoblast-like cell lines were cultured
      on uncoated and DLC-coated plates for periods of up to 72 h. The effects of DLC
      coatings on cellular metabolism were investigated by measuring the production of
      three osteoblast-specific marker proteins: alkaline phosphatase, osteocalcin, and
      type I collagen. There was no evidence that the presence of the DLC coating had
      any adverse effect on any of the parameters measured in this study. In a second
      series of experiments, DLC-coated cobalt-chromium cylinders were implanted in
      intramuscular locations in rats and in transcortical sites in sheep. Histologic
      analysis of specimens retrieved 90 days after surgery showed that the DLC-coated
      specimens were well tolerated in both sites. These data indicate that DLC
      coatings are biocompatible in vitro and in vivo, and further investigations into
      their long-term biological and tribological performance are now warranted.

PMID- 11319749
TI  - First histological observations on the incorporation of a novel calcium phosphate
      bone substitute material in human cancellous bone.
AB  - Calcium phosphates are frequently used as bone substitute materials because of
      their similarity to the mineral phase of bone, absence of antigenicity, and
      excellent osteoconductivity. However, in most currently available mineral
      substitutes, resorption occurs slowly if at all. In contrast, calcium phosphate
      cements have shown rapid resorption and remodeling in animal studies. In two
      prospective studies, a novel amorphous calcium phosphate cement (Biobon) was
      implanted in human patients for the first time. After 2-12 months, ten biopsies
      were obtained from nine individuals during secondary surgical interventions, for
      example, for implant removal. In all specimens, partial replacement of the
      material by new bone was observed, while residues of the cement were still
      visible. Undecalcified sections revealed extensive bone formation in immediate
      contact to the cement without fibrous interface. Polynucleated cells and
      superficial lacunae were indicative of resorptive activity, but inflammatory
      tissue response was absent. The new bone displayed regular trabecular and
      osteonal patterns. The histologic findings are in accordance with the excellent
      biocompatibility observed in the clinical follow-up. Though still incomplete, the
      resorbability of this cement appears superior to sintered calcium phosphates in
      these biopsy specimens. Presumably this is due to its amorphous crystalline
      structure. Biobon merits further studies as a promising substance for bone defect
      reconstruction in non-stress-bearing areas.

PMID- 11319750
TI  - Divergence and convergence of TGF-beta/BMP signaling.
AB  - The transforming growth factor-beta (TGF-beta) superfamily includes more than 30
      members which have a broad array of biological activities. TGF-beta superfamily
      ligands bind to type II and type I serine/threonine kinase receptors and
      transduce signals via Smad proteins. Receptor-regulated Smads (R-Smads) can be
      classified into two subclasses, i.e. those activated by activin and TGF-beta
      signaling pathways (AR-Smads), and those activated by bone morphogenetic protein
      (BMP) pathways (BR-Smads). The numbers of type II and type I receptors and Smad
      proteins are limited. Thus, signaling of the TGF-beta superfamily converges at
      the receptor and Smad levels. In the intracellular signaling pathways, Smads
      interact with various partner proteins and thereby exhibit a wide variety of
      biological activities. Moreover, signaling by Smads is modulated by various other
      signaling pathways allowing TGF-beta superfamily ligands to elicit diverse
      effects on target cells. Perturbations of the TGF-beta/BMP signaling pathways
      result in various clinical disorders including cancers, vascular diseases, and
      bone disorders.

PMID- 11319751
TI  - Nitric oxide chemistry and cellular signaling.
AB  - Nitric oxide (NO) has been shown to mediate a number of different physiological
      functions within every major organ system. This wide variety of functional roles
      is made all the more remarkable when one considers that NO is a simple diatomic
      molecule. However, despite the simplicity of the molecule, NO possesses a wide
      range of chemical reactivity and multiple potential reactive targets. It is the
      variability of NO reactivity, which leads to its capability to control such a
      vast range of biological functions. In essence the functionality of NO is
      controlled by its chemical reactivity. In order to understand this possibility
      further it is necessary to consider the biologically relevant reactions of nitric
      oxide.

PMID- 11319752
TI  - Antibodies against a putative heparin receptor slow cell proliferation and
      decrease MAPK activation in vascular smooth muscle cells.
AB  - Heparin has long been known to slow the growth of vascular smooth muscle cells.
      However, the mechanism(s) by which heparin acts has yet to be resolved. The
      identification of a putative heparin receptor in endothelial cells with
      antibodies that blocked heparin binding to the cells provided the means to
      further examine the possible involvement of a heparin receptor in smooth muscle
      cell responses to heparin. Immunoprecipitation of a smooth muscle cell protein
      with the anti-heparin receptor antibodies provided evidence that the protein was
      present in smooth muscle cells. Experiments with the anti-heparin receptor
      antibodies indicate that the antibodies can mimic heparin in decreasing PDGF
      induced thymidine and BrdU incorporation. The anti-heparin receptor antibodies
      were also found to decrease MAPK activity levels after activation similarly to
      heparin. These results support the identification of a heparin receptor and its
      role in heparin effects on vascular smooth muscle cell growth.

PMID- 11319753
TI  - IL-1- and TNF-induced bone resorption is mediated by p38 mitogen activated
      protein kinase.
AB  - We have previously shown that p38 mitogen-activated protein kinase (MAPK)
      inhibitors, which block the production and action of inflammatory cytokines such
      as tumor necrosis factor (TNF) and interleukin-1 (IL-1), are effective in models
      of bone and cartilage degradation. To further investigate the role of p38 MAPK,
      we have studied its activation in osteoblasts and chondrocytes, following
      treatment with a panel of proinflammatory and osteotropic agents. In osteoblasts,
      significant activation of p38 MAPK was observed following treatment with IL-1 and
      TNF, but not parathyroid hormone, transforming growth factor-beta (TGF-beta),
      1,25(OH)(2)D(3), insulin-like growth factor-1 (IGF-1), or IGF-II. Similar results
      were obtained using primary bovine chondrocytes and an SV40-immortalized human
      chondrocyte cell line, T/C28A4. SB 203580, a selective inhibitor of p38 MAPK,
      inhibited IL-1 and TNF-induced p38 MAPK activity and IL-6 production (IC(50)s 0.3
      -0.5 microM) in osteoblasts and chondrocytes. In addition, IL-1 and TNF also
      activated p38 MAPK in fetal rat long bones and p38 MAPK inhibitors inhibited IL-1
      and TNF-stimulated bone resorption in vitro in a dose-dependent manner (IC(50)s
      0.3--1 microM). These data support the contention that p38 MAPK plays a central
      role in regulating the production of, and responsiveness to, proinflammatory
      cytokines in bone and cartilage. Furthermore, the strong correlation between
      inhibition of kinase activity and IL-1 and TNF-stimulated biological responses
      indicates that selective inhibition of the p38 MAPK pathway may have therapeutic
      utility in joint diseases such as rheumatoid arthritis (RA).

PMID- 11319754
TI  - Regulatory volume decrease (RVD) by isolated and in situ bovine articular
      chondrocytes.
AB  - Articular chondrocytes in vivo are exposed to a changing osmotic environment
      under both physiological (static load) and pathological (osteoarthritis)
      conditions. Such changes to matrix hydration could alter cell volume in situ and
      influence matrix metabolism. However the ability of chondrocytes to regulate
      their volume in the face of osmotic perturbations have not been studied in
      detail. We have investigated the regulatory volume decrease (RVD) capacity of
      bovine articular chondrocytes within, and isolated from the matrix, before and
      following acute hypotonic challenge. Cell volumes were determined by visualising
      fluorescently-labelled chondrocytes using confocal laser scanning microscopy
      (CLSM) at 21 degrees C. Chondrocytes in situ were grouped into superficial (SZ),
      mid (MZ), and deep zones (DZ). When exposed to 180mOsm or 250mOsm hypotonic
      challenge, cells in situ swelled rapidly (within approximately 90 sec).
      Chondrocytes then exhibited rapid RVD (t(1/2) approximately 8 min), with cells
      from all zones returning to approximately 3% of their initial volume after 20
      min. There was no significant difference in the rates of RVD between chondrocytes
      in the three zones. Similarly, no difference in the rate of RVD was observed for
      an osmotic shock from 280 to 250 or 180mOsm. Chondrocytes isolated from the
      matrix into medium of 380mOsm and then exposed to 280mOsm showed an identical RVD
      response to that of in situ cells. The RVD response of in situ cells was
      inhibited by REV 5901. The results suggested that the signalling pathways
      involved in RVD remained intact after chondrocyte isolation from cartilage and
      thus it was likely that there was no role for cell-matrix interactions in
      mediating RVD.

PMID- 11319755
TI  - Regulation of alpha-smooth muscle actin and CRBP-1 expression by retinoic acid
      and TGF-beta in cultured fibroblasts.
AB  - We have reported that Cellular Retinol Binding Protein-1 (CRBP-1) is expressed de
      novo during skin wound healing by a proportion of fibroblastic cells which then
      differentiate into myofibroblasts and express alpha-smooth muscle actin. In
      fibroblasts cultured from different tissues we have shown that alpha-smooth
      muscle actin expression, mainly controlled by Transforming Growth Factor-beta
      (TGF-beta), is also regulated by retinoic acid and that CRBP-1, known to be a
      retinoic acid-responsive gene, is modulated by TGF-beta. The aim of the present
      study has been to investigate the relationships between retinoic acid and TGF
      beta in regulating the expression of CRBP-1 and alpha-smooth muscle actin in
      cultured rat subcutaneous tissue fibroblasts. We have observed that the TGF-beta
      induced, but not the retinoic acid-induced, alpha-smooth muscle actin expression
      is associated with a modulation of endogenous TGF-beta and TGF-beta receptors,
      suggesting that the action of retinoic acid on alpha-smooth muscle actin
      expression is not mediated by TGF-beta. The expression of CRBP-1 is regulated at
      the transcriptional level by TGF-beta and retinoic acid but not synergistically,
      suggesting a possible common pathway. However, retinoic acid, but not TGF-beta,
      increases the transcription of a transiently transfected chimeric construct
      containing the retinoic acid response element of the CRBP-1 promoter, indicating
      that TGF-beta does not influence CRBP-1 through the retinoic acid pathway. Our
      results indicate that distinct pathways regulate the genes involved in the
      appearance and evolution of the myofibroblastic cells. The characterization of
      these pathways will be helpful for the design of drugs influencing wound healing.

PMID- 11319756
TI  - Angiotensin II type 1 receptor regulation and differential trophic effects on rat
      cardiac myofibroblasts after acute myocardial infarction.
AB  - Fibroblast growth in the scar and surviving tissue is a key element of the
      remodeling post myocardial infarction. The regulation of fibroblast growth after
      acute myocardial infarction remains to be determined. Recently, Angiotensin II
      has been demonstrated to be a mitogen for neonatal cardiac fibroblasts. In this
      study adult rat cardiac fibroblasts were isolated from different regions of the
      infarcted rat heart and Angiotensin II effects examined. Adult Wistar-rats were
      sham operated or left coronary artery ligated. After 4 days, hearts were removed
      and fibroblasts from sham operated, infarct- and non-infarct regions of the left
      ventricle isolated. Radioligand binding studies were performed and cell number,
      cell area, total protein, and AT(1) receptor mRNA after stimulation determined.
      Radioligand binding studies demonstrated that myofibroblasts expressed a single
      class of high affinity Angiotensin II AT(1) receptors. Myofibroblasts from the
      infarct area revealed a lower maximal binding capacity, compared to sham operated
      myocardium. Conversely, myofibroblasts from the non-infarct area had a higher
      expression of Angiotensin II AT(1) receptor mRNA compared to sham operated
      myofibroblasts. Angiotensin II (1 microM, 48 h) increased cell-number in sham
      operated and non-infarct, but not in infarct myofibroblasts. Angiotensin II
      elevated total protein in sham operated, non-infarct, and infarct myofibroblasts.
      In addition, Angiotensin II increased cell area in sham operated and infarct
      myofibroblasts. These data demonstrate that Angiotensin II acted as a mitogen in
      sham operated and non-infarct myofibroblasts and stimulated hypertrophy in
      infarct myofibroblasts. These regional different effects of Angiotensin II might
      participate in the remodeling post myocardial infarction.

PMID- 11319757
TI  - Stimulation of DNA synthesis by tumor promoters in primary rat hepatocytes is not
      mediated by arachidonic acid metabolites.
AB  - Studies in vivo using inhibitors of eicosanoid synthesis suggested that
      prostaglandins may play a role in mediating tumor promotion in liver by agents
      such as phenobarbital (PB). However, it is not clear whether any stimulation of
      arachidonic acid metabolism/prostaglandin formation results directly from the
      action of tumor promoters on hepatocytes or indirectly from effects of promoters
      on Kupffer cells or other non-hepatocytes. Our laboratory has been utilizing
      relatively pure populations of rat hepatocytes under the defined conditions of
      primary cultures, to investigate growth-stimulatory actions of tumor promoters,
      an important element in the promotion stage of carcinogenesis. It has been shown
      that most if not all liver tumor promoters tested stimulate hepatocyte DNA
      synthesis when added in combination with factors such as EGF, insulin, and
      glucocorticoid. In the present study, we sought evidence for a role of
      prostaglandins (PGs) in the direct growth-stimulatory actions of tumor promoters
      on hepatocytes. PGE(2), PGF(2 alpha), and PGD(2) cause concentration-dependent
      stimulation of hepatocyte DNA synthesis, while arachidonic acid was without any
      effect. PGE(2) and PGF(2 alpha) required the presence of dexamethasone to exert
      significant effects. These PGs did not further augment the stimulatory effect of
      EGF. In contrast, PGD(2) stimulated DNA synthesis in the presence or absence of
      insulin, dexamethasone, or EGF. The effect of tumor promoters on arachidonic acid
      metabolism, as measured by [(3)H]arachidonic acid release and PGE(2) production,
      was determined. The phorbol ester TPA significantly increased [(3)H]arachidonic
      acid release as well as PGE(2) formation in hepatocytes in line with known
      effects in other cell types. However, liver tumor promoters phenobarbital (PB),
      alpha-hexachlorocycohexane (HCH), 1,1-bis(p-chlorophenyl)-2,2,2-trichloroethane
      (DDT), and pregnenolone-16 alpha-carbonitrile (PCN) were without effects.
      Finally, inhibitors of arachidonic acid metabolism were tested for effects on the
      ability of TPA or liver tumor promoters to stimulate DNA synthesis by direct
      action on cultured hepatocytes. In all cases, lack of selective inhibition was
      observed. Taken together, the results show that while prostaglandins may directly
      stimulate DNA synthesis in hepatocytes, they are unlikely to mediate the direct
      growth-stimulatory actions of liver tumor promoters.

PMID- 11319758
TI  - Cultivation of rat marrow-derived mesenchymal stem cells in reduced oxygen
      tension: effects on in vitro and in vivo osteochondrogenesis.
AB  - Rat mesenchymal stem cells (rMSCs) represent a small portion of the cells in the
      stromal compartment of bone marrow and have the potential to differentiate into
      bone, cartilage, fat, and fibrous tissue. These mesenchymal progenitor cells were
      maintained as primary isolates and as subcultured cells in separate closed
      modular incubator chambers purged with either 95% air and 5% CO(2) (20% or
      control oxygen) or 5% oxygen, 5% CO(2), and 90% nitrogen (5% or low oxygen). At
      first passage, some cells from each oxygen condition were loaded into porous
      ceramic vehicles and implanted into syngeneic host animals in an in vivo assay
      for osteochondrogenesis. The remaining cells were continued in vitro in the same
      oxygen tension as for primary culture or were switched to the alternate
      condition. The first passage cells were examined for in vitro osteogenesis with
      assays involving the quantification of alkaline phosphatase activity and calcium
      and DNA content as well as by von Kossa staining to detect mineralization.
      Cultures maintained in low oxygen had a greater number of colonies as primary
      isolates and proliferated more rapidly throughout their time in vitro, as
      indicated by hemacytometer counts at the end of primary culture and increased DNA
      values for first passage cells. Moreover, rMSCs cultivated in 5% oxygen produced
      more bone than cells cultured in 20% oxygen when harvested and loaded into porous
      ceramic cubes and implanted into syngeneic host animals. Finally, markers for
      osteogenesis, including alkaline phosphatase activity, calcium content, and von
      Kossa staining, were elevated in cultures which had been in low oxygen throughout
      their cultivation time. Expression of these markers was usually increased above
      basal levels when cells were switched from control to low oxygen at first passage
      and decreased for cells switched from low to control oxygen. We conclude that
      rMSCs in culture function optimally in an atmosphere of reduced oxygen that more
      closely approximates documented in vivo oxygen tension.

PMID- 11319759
TI  - Growth inhibition due to complementation of transforming growth factor-beta
      receptor type II-defect by human chromosome 3 transfer in human colorectal
      carcinoma cells.
AB  - The transforming growth-beta receptor type II (TGF-beta RII) gene is one of the
      target genes of the DNA mismatch repair (MMR) defect. The human colorectal
      carcinoma cell line HCT116 has mutations in the hMLH1 gene and in the
      microsatellite region of the TGF-beta RII gene, both located on the short arm of
      chromosome 3. Introduction of the wild-type hMLH1 gene on transferred human
      chromosome 3 restores many characteristics of MMR-deficiency in HCT116. In this
      study, we determined whether transfer of chromosome 3 into HCT116 also
      complements the TGF-beta RII gene defect. We compared in vitro growth
      characteristics between HCT116 and HCT116 with a transferred chromosome 3 (HCT116
      + ch3). The growth was suppressed in HCT116 + ch3 compared with parental HCT116.
      This suppression was abolished by frequent replacement with fresh medium,
      suggesting that the autocrine TGF-beta-TGF-beta RII system may be responsible for
      growth suppression. To explore this possibility, we determined several
      characteristics essential for the autocrine system. We found that HCT116 + ch3
      expresses wild-type as well as mutated TGF-beta RII mRNA. In addition,
      phosphorylation of TGF-beta RI and growth inhibition were observed in HCT116 +
      ch3 but not in HCT116 by exposure to exogenous TGF-beta. The amount of TGF-beta1
      in HCT116 + ch3 cultures was remarkably less than that in the HCT116, suggesting
      that TGF-beta produced by HCT116 + ch3 cells may be consumed by the cells. The
      conditioned medium from HCT116 cultures inhibits HCT116 + ch3 growth. This
      inhibition was neutralized by the anti-TGF-beta antibody. Taken together, these
      results strongly suggest that the TGF-beta RII gene defect in HCT116 is
      complemented by a wild-type gene on the transferred chromosome 3 and that HCT116
      + ch3 gained the ability to respond to TGF-beta. Simultaneous complementation of
      defects of a responsible gene and a major target gene by the chromosome transfer
      is useful to prove the inactivated phenotypes acquired during colorectal
      tumorigenesis.

PMID- 11319760
TI  - Na(+)/K(+) pump expression in the L8 rat myogenic cell line: effects of
      heterologous alpha subunit transfection.
AB  - We have characterized the physiological and biochemical properties of the
      Na(+)/K(+) pump and its molecular expression in L8 rat muscle cells. Pump
      properties were measured by [(3)H]ouabain binding and (86)Rb uptake. Scatchard
      plot analysis of specific ouabain binding indicated the presence of a single
      family of binding sites with a B(max) of approximately 135 fmol/ mg P and a K(D)
      of 3.3 x 10(-8). (86)Rb uptake due to specific pump activity was found to be 20%
      of the total in L8 cells. The results indicated lower affinity of L8 cells for
      ouabain and lower activity of the pump than that reported for chick or rat
      skeletal muscle in primary culture. Both the alpha(1) and beta(1) protein and
      mRNA isoforms were expressed in myoblasts and in myotubes, while the alpha(2),
      alpha(3), and beta(2) isoforms were not detectable. We attempted to overcome low
      physiological expression of the Na(+)/K(+) pump by employing a vector expressing
      an avian high affinity alpha subunit. This allowed identification of the
      transfected subunit separate from that endogenously expressed in L8 cells.
      Successful transfection into L8 myoblasts and myotubes was recognized by anti
      avian alpha subunit monoclonal antibodies. Fusion index, Na(+)/K(+) pump
      activity, and the level of the transmembrane resting potential were all
      significantly greater in transfected L8 (tL8) cells than in non-tL8. The total
      amount of alpha subunit (avian and rat) in tL8 cells was greater than that (only
      rat) in non-tL8 cells. This relatively high abundance of the Na(+)/K(+) pump in
      transfected cells may indicate that avian and rat alpha subunits hybridize to
      form functional pump complexes.

PMID- 11319761
TI  - Possible involvement of reactive oxygen species in D-galactosamine-induced
      sensitization against tumor necrosis factor-alpha-induced hepatocyte apoptosis.
AB  - Intravenous administration of tumor necrosis factor-alpha (TNF-alpha) (0.5
      microg/mouse) caused hepatocyte apoptosis in BALB/c mice when they were
      sensitized with D-galactosamine (GalN, 20 mg/mouse). Activation of nuclear factor
      kappa B (NF-kappa B) and expression of apoptotic Bcl-2 family members were not
      significantly different between livers of mice treated with TNF-alpha alone and
      GalN + TNF-alpha, indicating that neither activation of NF-kappa B nor expression
      of Bcl-2 family is involved in the sensitization by GalN against TNF-alpha
      induced hepatocyte apoptosis. To identify differentially expressed genes
      implicated in GalN-induced hepatocyte sensitization, we adopted mRNA
      fingerprinting using an arbitrarily primed polymerase chain reaction. The present
      analysis revealed that mRNA expression of extracellular antioxidant,
      selenoprotein P, was up-regulated in the livers after GalN administration. GalN
      induced increase in its protein level was confirmed by Western blotting.
      Increased expression of this gene was also observed in the liver of mice treated
      with concanavalin A, but not anti-Fas antibody. mRNA of another antioxidant,
      glutathione peroxidase-1, was also up-regulated, and lipid peroxides were
      produced in the liver after GalN administration. Selenoprotein P mRNA level also
      increased in Huh-7 human hepatoma cells incubated with GalN (5 or 10 mM).
      Accordingly, formation of reactive oxygen species (ROS) was observed in GalN
      treated Huh-7 cells. H(2)O(2) induced up-regulation of selenoprotein P mRNA and
      sensitized Huh-7 cells to TNF-alpha-induced apoptosis. These results suggest that
      ROS produced by GalN may play a pivotal role in hepatocyte sensitization toward
      TNF-alpha-induced apoptosis.

PMID- 11319762
TI  - Growth and characterization of a cell line from a human primary neuroendocrine
      carcinoma of the skin (Merkel cell carcinoma) in culture and as xenograft.
AB  - The primary neuroendocrine carcinoma of the skin or Merkel cell carcinoma (MCC)
      is a skin tumor with aggressive biological behaviour. Experimental models for
      investigating the biological properties of the tumor are prerequisite for
      developing new therapeutic approaches. In this study, we report the establishment
      and characterisation of a cell line derived from the lymph-node metastasis of a
      patient with highly aggressive MCC. Merkel carcinoma cells (MCC-1) grew as
      floating aggregates in suspension cultures for more than two years and over 70
      subcultures. The proliferation rate in suspension cultures was rather moderate
      with a population doubling time of 69 h. The immunocytochemical pattern of the
      cultured MCC-1 was similar to that of the original tumor with expression of
      cytokeratin 18, neuron-specific enolase, neurofilaments, and synaptophysin. In
      addition, reverse transcriptase polymerase chain reaction (RT-PCR) revealed
      presence of chromogranin A mRNA in the MCC-1 cell line. Furthermore, electron
      microscopy yielded the rare finding of neuroendocrine granules in the cytoplasm
      of the cultured cells. The cell line MCC-1 was able to form colonies in soft
      agar. Nude mice developed solid tumors with similar histology to the original
      tumor after subcutaneous and intravenous injections of cultured MCC-1, and
      malignant ascites was seen after intraperitoneal injection. Also, two MCC-1
      sublines were established by reculturing cells from the xenografts grown in vivo
      and immunocytochemistry confirmed their neuroendocrine origin. The MCC-1 line may
      thus serve as a model for studying the biology and the metastatic potential of
      Merkel cell carcinoma.

PMID- 11319763
TI  - Reduction of telomerase activity in human liver cancer cells by a histone
      deacetylase inhibitor.
AB  - The presence of telomerase has been demonstrated recently in many different
      malignancies. Several reports documented that in human hepatocellular carcinoma,
      the level of telomerase activity parallels its differentiation stage. In the
      present study, the effect of the differentiation-inducing agent sodium butyrate
      on telomerase activity in four human liver cancer cell lines was investigated
      using the telomeric repeat amplification protocol. We assayed telomerase activity
      before and after butyrate treatment and in cell cycle synchronized non-dividing
      quiescent cells. In addition, telomerase reverse transcriptase levels were
      measured at the mRNA level. All four cell lines possessed high but not identical
      levels of telomerase activity. Telomerase activity was significantly reduced by
      treatment with sodium butyrate as well as trichostatin A in a dose- and time
      dependent fashion, paralleling the reduction of cell proliferation. Although
      methotrexate, hydroxyurea, and colchicine synchronized the cell cycle at G1, S,
      and G2/M, respectively, and thereby also caused proliferating cells to cease
      dividing and become quiescent, in this case telomerase activity remained
      essentially unaltered compared to the control cultures. Moreover, levels of mRNA
      encoding telomerase reverse transcriptase were not always significantly altered
      by either sodium butyrate treatment or cell cycle synchronization. These results
      suggest that sodium butyrate, as a histone deacetylase inhibitor, effectively
      reduces telomerase activity without affecting transcription levels of the reverse
      transcriptase component.

PMID- 11319764
TI  - The lack of effect of acute hyperglycemia on visual cortical activation.

PMID- 11319765
TI  - Glial transporters for glutamate, glycine, and GABA III. Glycine transporters.
AB  - Glial cells possess transport systems for the three major amino acid
      neurotransmitters glutamate, gamma-aminobutyric acid (GABA) and glycine, involved
      in the arrest of neurotransmission mediated by these compounds. Two glycine
      transporters have been cloned: GLYT1, mainly expressed by glial cells and shown
      to colocalize with NMDA receptors, and GLYT2, exclusively expressed by neurons
      and colocalized with the inhibitory glycine receptors. The way in which the
      regulation of extracellular glycine concentration by glial glycine transporters
      affects physiological and pathological conditions is discussed. The presence,
      differential pharmacology and specific regulation of glycine transporters in
      glial cells strongly support an important role for glia in the modulation of
      both, excitatory and inhibitory neurotransmission.

PMID- 11319766
TI  - Differential NF-kappa B regulation of bcl-x gene expression in hippocampus and
      basal forebrain in response to hypoxia.
AB  - Cell death often occurs after hypoxic/ischemic injury to the central nervous
      system. Changes in levels of the anti-apoptotic Bcl-X(L) protein may be a
      determining factor in hypoxia-induced neuronal apoptosis. The transcription
      factor NF-kappa B regulates bcl-x gene expression. In this study, we examined the
      role of NF-kappa B in the regulation of bcl-x in hypoxia-induced cell death. Rat
      hippocampus and basal forebrain tissues were collected at different time points
      after hypoxia (7%O(2), 93% N(2) for 10 or 20 min). We found that 1) hypoxia
      induced apoptosis in the hippocampus and basal forebrain; 2) the NF-kappa B
      dimers c-Rel/p50 and p50/p50 bound to the bcl-x promoter NF-kappa B sequence
      (CS4) in the hippocampus, but only p50/p50 bound to the CS4 sequence in the basal
      forebrain and hypoxia-induced differential binding patterns of c-Rel/p50 and
      p50/p50 correlated with the bcl-x expression pattern in the hippocampus; 3) the
      hypoxia-induced patterns of binding of c-Rel/p50 to the bcl-x promoter CS4
      sequence were different from those to the IgG-kappa B enhancer sequence, whereas
      those of p50/p50 were similar to both sequences; 4) nuclear protein levels of c
      Rel, but not p50, correlated with the c-Rel/p50 DNA binding patterns to the bcl-x
      CS4 site; and 5) there were differential responses to hypoxia among the different
      NF-kappa B protein subunits. These results suggest that there is a tissue
      specific regulation of bcl-x gene expression by NF-kappa B in hypoxia-induced
      cell death in the hippocampus. The absence of these regulating features in the
      basal forebrain may account for the early appearance of apoptosis in response to
      hypoxia as compared with that in hippocampus.

PMID- 11319767
TI  - Calcium-dependent association of annexin VI, protein kinase C alpha, and
      neurocalcin alpha on the raft fraction derived from the synaptic plasma membrane
      of rat brain.
AB  - A membrane microdomain enriched in cholesterol and sphingolipids or so called
      "raft" region was found to contain many signal transducing proteins such as GPI
      anchored proteins, trimeric G proteins and protein tyrosine kinases. Because
      brain-derived raft contains two calmodulin-binding proteins, GAP-43 and NAP-22 as
      the major protein components, the raft domain is assumed to be important in the
      Ca(2+)-signaling. In this study, we analyzed protein components showing Ca(2+)
      dependent binding to the raft of synaptic plasma membrane from rat brain. SDS
      PAGE analysis of the protein components in the EGTA eluate from the raft prepared
      in the presence of Ca(2+)-ions showed the elution of 80 kDa, 68 kDa, 22 kDa, and
      21 kDa proteins. These proteins were identified as protein kinase C alpha (80
      kDa) and annexin VI (68 kDa) from the partial amino-acid sequencing, and
      neurocalcin alpha (22 kDa) and calmodulin (21 kDa) with western blotting and
      electrophoretic mobilities in the presence or absence of Ca(2+) ions. Further
      immunoblotting experiments showed the Ca(2+)-dependent association of
      conventional, but not non-conventional, subtypes of PKC to the raft.

PMID- 11319768
TI  - Differential regulation of GDNF, neurturin, and their receptors in primary
      cultures of rat glial cells.
AB  - Glial cell line-derived neurotrophic factor (GDNF) and neurturin (NTN) bind to
      GFR alpha-1 and GFR alpha-2 receptors, respectively, and their neurotrophic
      activity is mediated by the tyrosine kinase receptor, Ret. All these molecules
      were found to be expressed in primary cultures of rat glial cells, which were
      largely composed of astrocytes and maintained in serum-free medium. Although
      GDNF, NTN and Ret mRNA levels were at the limit of detection, RNase protection
      assays revealed relatively high amounts of GFR alpha-1 and GFR alpha transcripts.
      To characterize signals controlling their expression, glial cells were exposed to
      serum or treated with hormones acting through nuclear receptors and by activators
      of the cAMP or protein kinase C (PKC)-dependent pathways. Retinoic acid or 1,25
      dihydroxyvitamin D3 appeared ineffective. In contrast, the 5-fold increase in GFR
      alpha-2 mRNA after 24 hr of treatment with 10(-10) M of tri-iodothyronine,
      suggests a physiological role of thyroid hormone in the regulation of this
      receptor in vivo. The serum induced a 7-fold increase in GFR alpha-1 mRNA levels.
      These changes may be mediated by the cAMP or PKC pathways because both forskolin
      and TPA up-regulated the GFR alpha-1 gene. Interestingly, only TPA led to a
      coordinated increase in the levels of GDNF, GFR alpha-1 and GFR alpha-2 mRNAs. On
      the other hand, NTN transcripts remained constant, irrespective of the culture
      conditions. Taken together, these results indicate that GDNF family ligands and
      their receptors are regulated in glial cells by common or independent
      transductional pathways, which could modulate their specific expression during
      brain development or in the case of trauma.

PMID- 11319769
TI  - Differential regulation of telomerase activity and TERT expression during brain
      development in mice.
AB  - Telomerase is an enzyme activity consisting of a reverse transcriptase called
      TERT and an RNA component that adds repeats of a DNA sequence (TTAGGG) to the
      ends of chromosomes, thereby preventing their shortening. Associations between
      telomerase activity and proliferation and differentiation of neural tumor cells
      and neural stem cells have been reported, but the role of telomerase in brain
      development is unknown. We now report analyses of telomerase activity, TERT mRNA
      levels and levels of mRNAs encoding the telomere-associated proteins TRF1 and
      TRF2 in three different brain regions (brainstem, hippocampus and cerebral
      cortex) and the eye of mice at increasing developmental time points. Telomerase
      activity is high in the brain at embryonic day 13 (E13), declines markedly
      between E13 and E18, remains at a low level until postnatal day 3 (P3) and
      becomes undetectable by P10. Surprisingly, the temporal pattern of change in
      telomerase activity is not paralleled by a decrease in levels of TERT mRNA that
      remain elevated from E13 to P5 (with fluctuations during this time window that
      vary among brain regions), and then decrease to a lower level that is maintained
      into adulthood. TRF1 and TRF2 mRNA levels are relatively constant throughout
      brain development. Our data are consistent with a role for telomerase activity in
      proliferation of neural progenitor cells, and further suggest that TERT may play
      roles in neuronal differentiation and survival. The dissociation between TERT
      expression and telomerase activity is a novel finding that suggests biological
      functions for TERT in addition to telomere maintenance. J. Neurosci. Res. 64:252
      260, 2001. Published 2001 Wiley-Liss, Inc.

PMID- 11319770
TI  - Serotonin regulation of nerve growth factor synthesis in neonatal and adult
      astrocytes: comparison to the beta-adrenergic agonist isoproterenol.
AB  - Although serotonin regulates synthesis of the neurotrophic factor S-100 beta by
      astrocytes, its ability to affect nerve growth factor (NGF) synthesis has never
      been examined. We report here that there is a correlation between the effect of
      serotonin on cyclic adenosine monophosphate (cAMP) content and on NGF content in
      neonatal astrocytes but not in adult astrocytes. In neonatal striatal astrocytes,
      serotonin increases both cAMP and NGF, whereas, in neonatal cerebellar
      astrocytes, serotonin decreases both. The increase in neonatal cortical astrocyte
      cAMP appeared to be too small (45%) to increase NGF significantly. The beta
      adrenergic agonist isoproterenol increased cAMP and NGF in both cortical and
      striatal astrocytes derived from neonatal rats. In contrast, there was a
      dissociation between cAMP changes and NGF changes in astrocytes derived from
      adult rats. Both serotonin and isoproterenol increased cAMP in adult cortical
      astrocytes, without any effect on NGF content. However, adult striatal astrocytes
      responded to serotonin with an elevation of both cAMP and NGF, whereas
      isoproterenol could only enhance cAMP, without affecting NGF. Thus, in neonatal
      astrocytes, a change of sufficient magnitude in cAMP was correlated with a
      comparable change in NGF, in response to activation of either serotonergic or
      beta-adrenergic receptors; in cerebellar astrocytes, the decrease in cAMP was
      accompanied by a decrease in NGF. In contrast, adult astrocytes were not
      responsive: Although cAMP changes were large, NGF synthesis was increased only in
      striatal astrocytes and only in response to serotonin. J. Neurosci. Res. 64:261
      267, 2001. Published 2001 Wiley-Liss, Inc.

PMID- 11319772
TI  - Adrenocorticosteroid receptor blockade and excitotoxic challenge regulate
      adrenocorticosteroid receptor mRNA levels in hippocampus.
AB  - The mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) are
      glucocorticoid-activated transcription factors essential for maintenance of
      cellular homeostasis. Differential activation of these adrenocorticosteroid
      receptors (ACR) is thought to influence neuronal viability, particularly under
      challenging cellular conditions. The present study is designed to determine the
      effects of receptor blockade and excitotoxic insult on MR and GR mRNA expression
      and neuronal viability in hippocampus. Male Sprague--Dawley rats were pretreated
      for 48 hr with vehicle, MR antagonist spironolactone (SPIRO) (50 mg/kg, twice
      daily, s.c.), or GR antagonist RU486 (25 mg/kg, twice daily, s.c.) and
      subsequently injected with saline or the glutamate analog kainic acid (KA) (12
      mg/kg i.p.). Twenty-four hr post-insult, MR and GR mRNA levels were assessed by
      in situ hybridization analysis, and hippocampal neurons were counted to assess KA
      induced cell loss. MR blockade with SPIRO increased basal MR mRNA levels in
      hippocampal subregions CA1, CA3, and dentate gyrus (DG) and increased basal GR
      mRNA levels in CA3. GR blockade with RU486 increased basal GR mRNA levels in CA3.
      The excitotoxin KA decreased MR mRNA levels in CA1 and CA3, decreased GR mRNA
      levels in DG, and negated all antagonist-induced increases of ACR mRNAs. Cell
      counts quantifying KA damage indicated increased CA3 vulnerability to KA insult
      after treatment with MR antagonist spironolactone but demonstrated no significant
      cell loss in any other group or region. These results demonstrate dynamic
      regulation of hippocampal MR and GR mRNAs after ACR antagonist treatment and
      kainate toxicity, underscoring the potential importance of MR and GR availability
      to neuronal viability after insult.

PMID- 11319771
TI  - Absence of hippocampal mossy fiber sprouting in transgenic mice overexpressing
      brain-derived neurotrophic factor.
AB  - Excess neuronal activity upregulates the expression of two neurotrophins, nerve
      growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in adult
      hippocampus. Nerve growth factor has been shown to contribute the induction of
      aberrant hippocampal mossy fiber sprouting in the inner molecular layer of the
      dentate gyrus, however the role of prolonged brain-derived neurotrophic factor
      exposure is uncertain. We examined the distribution and plasticity of mossy
      fibers in transgenic mice with developmental overexpression of brain-derived
      neurotrophic factor. Despite 2--3-fold elevated BDNF levels in the hippocampus
      sufficient to increase the intensity of neuropeptide Y immunoreactivity in
      interneurons, no visible changes in mossy fiber Timm staining patterns were
      observed in the inner molecular layer of adult mutant hippocampus compared to
      wild-type mice. In addition, no changes of the mRNA expression of two growth
      associated proteins, GAP-43 and SCG-10 were found. These data suggest that early
      and persistent elevations of brain-derived neurotrophic factor in granule cells
      are not sufficient to elicit this pattern of axonal plasticity in the
      hippocampus.

PMID- 11319773
TI  - Role of oxidative stress in the apoptotic cell death of cultured cerebellar
      granule neurons.
AB  - When cultured cerebellar granule neurons (CGN) are transferred from 25 mM KCl
      (K25) to 5 mM KCl (K5) caspase-3 and caspase-8, but not caspase-1 or caspase
      9,activities are induced and cells die apoptotically. CGN death was triggered by
      a [Ca(2+)](i) modification when [Ca(2+)](i) was reduced from 300 nM to 50 nM in a
      K5 medium. The [Ca(2+)](i) changes were followed by an increase in ROS levels.
      The generation of both cytosolic and mitochondrial reactive oxygen species (ROS)
      occurred at three different times, 10 min, 30 min and 3--4 hr but only those ROS
      produced after 3--4 hr are involved in the process of cell death. When CGN
      cultured in a K5 medium are treated with different antioxidants like scavengers
      of ROS (mannitol, DMSO) or antioxidant enzymes (superoxide dismutase and
      catalase) phosphatidylserine translocation, caspase activity, chromatin
      condensation and cell death is markedly diminished. The protective effect of
      antioxidants is not mediated through a modification in [Ca(2+)](i). Caspase
      activation, PS translocation and chromatin condensation were downstream of ROS
      production. In contrast to H(2)O(2), ROS produced by a xanthine/xanthine oxidase
      system in CGN cultured in K25 were able to directly induce caspase-3 activation
      and death that resulted sensitive to z-VAD, a caspase inhibitor. These findings
      indicate that a reduction in [Ca(2+)](i) triggers CGN death by inducing a
      generation of ROS after 3--4 hr, which could play a critical role in the initial
      phases of the apoptotic process including PS translocation, chromatin
      condensation and the activation of initiator and executor caspases.

PMID- 11319774
TI  - Vaccination with a CDR2 BV6S2/6S5 peptide in adjuvant induces peptide-specific T
      cell responses in patients with multiple sclerosis.
AB  - Earlier studies from several groups including ours have documented that patients
      with multiple sclerosis (MS) have over-expression of activated T-cells from
      specific TCR V beta families, including BV6S2/S5 (Kotzin et al. [1991] Proc.
      Natl. Acad. Sci. USA 88:9161--9165; Gold et al. [1997] J. Neuroimmunol. 76:29-
      38). It has also been established in the rat EAE model that peptide vaccines to
      the over-expressed V beta 8.2 TCR can prevent MBP induced disease (Vandenbark et
      al. [1989] Nature 341:541--544). In the current clinical study, 10 patients were
      vaccinated with 300 microg of BV6S2/6S5 peptide emulsified in incomplete Freund's
      adjuvant (IFA) and monitored for safety and immunogenicity in a 48-week
      multicenter, open-label trial. The peptide vaccine was well tolerated and no
      serious adverse events were observed. Vaccinations induced cell-mediated immunity
      to the immunizing peptide in eight of 10 patients as demonstrated by lymphocyte
      proliferation assay (LPA) and delayed-type hypersensitivity (DTH) skin test
      responses. In summary, these results demonstrate that immunization with TCR
      BV6S2/6S5 peptide vaccine in MS patients is safe and immunogenic, and supports a
      larger double-blind placebo controlled trial to determine the clinical efficacy
      of this approach.

PMID- 11319775
TI  - Identifying genes involved in regulating differentiation of neuroblastoma cells.
AB  - The genes regulating the induction of differentiation in neurons are not
      definitively known. Some neuronal tumors retain the ability to differentiate into
      mature, functional neurons in response to pharmacological agents, despite the
      presence of genetic anomalies. We hypothesized that some of the genes whose
      expression is altered between undifferentiated and differentiated states may be
      those responsible for inducing differentiation. To investigate this, we used a
      mouse neuroblastoma (NB) cell line, NBP(2), in which > or =90% of the cells in
      the culture terminally differentiate upon elevation of intracellular adenosine
      3',5'-cyclic monophosphate (cAMP) levels. Gene expression was analyzed using cDNA
      array blots containing 588 known genes. mRNA from cultures of undifferentiated
      and differentiated NB cells was used to make cDNA probes for blot hybridization.
      We identified several genes that are predominantly expressed in either
      undifferentiated or differentiated NB cells. In addition, numerous genes are
      moderately up- or down-regulated during differentiation of NB cells. We
      identified the N-myc protooncogene, cyclin B1, and protease nexin 1 as genes that
      are expressed in undifferentiated NB cells and whose levels are significantly
      down-regulated upon differentiation. In contrast, the c-fes and c-fos
      protooncogenes and the RAG-1 gene activator are genes whose expression is
      significantly up-regulated during differentiation of NB cells. These findings
      were confirmed by RT-PCR analysis. The transcript size and expression level of N
      myc, cyclin B1, protease nexin 1, c-fes, and c-fos were verified by Northern
      blotting. These genes may represent key mediators involved in the regulation of
      NB cell differentiation.

PMID- 11319776
TI  - Thresholds for sweet, salt, and sour taste stimuli in cockatiels (Nymphicus
      hollandicus).
AB  - Little is known about avian taste perception and how taste affects food choice.
      We designed a study to determine the concentrations of aqueous solutions of
      common chemical taste stimuli that result in altered consumption patterns. Using
      two-choice taste-preference tests, we studied the taste thresholds of caged
      cockatiels (Nymphicus hollandicus) for aqueous solutions of potassium chloride, a
      phosphate buffer (to test pH), fructose, and glucose. First, the preferred and
      nonpreferred bottle locations were determined for each bird. Then, depending on
      the compound, the test solutions were placed in bottles in either the preferred
      or the nonpreferred locations and water was placed in the opposite bottle. Four
      parameters were measured at the end of 3-day test periods (total consumption,
      consumption from water side, consumption from test solution side, and proportion
      of nonpreferred side consumption to total consumption). Experiments were repeated
      with increasing concentrations of test flavors until intake variables were
      significantly affected (P < 0.05). Cockatiels distinguished (P < 0.05) between
      purified water and 0.16 mol L(-1) potassium chloride, 0.40 mol L(-1) fructose, or
      0.16 mol L(-1) glucose. The test birds did not distinguish between water and 0.05
      mol L(-1) mono- and dibasic sodium phosphate buffer solution at any tested pH
      within the range of 4.9-7.7. When these findings are compared to previous
      experiments with the same birds, it becomes clear that the gustatory reactions of
      cockatiels for two different stimuli (e.g., NaCl and KCl) from the same general
      taste category (salt, sweet, sour) can vary widely. This variation in the
      responses to related stimuli could be the result of a number of factors including
      anion effects (for salts and acids) as well as nongustatory physiological
      processes (e.g., as renal control of blood osmolarity). Zoo Biol 20:1-13, 2001.
      Copyright 2001 Wiley-Liss, Inc.

PMID- 11319777
TI  - Behavior of captive Bulwer's wattled pheasants, Lophura bulweri (Galliformes:
      Phasianidae).
AB  - Bulwer's wattled pheasant (Lophura bulweri) have traditionally been housed in
      pairs in captivity, although it is unknown whether monogamy is the species'
      natural mating system. In 1998 we placed our group of 3.3 L. bulweri together in
      a complex outdoor habitat, in order to investigate several questions. These
      included whether monogamous pairing was the natural mating system for the
      species, how the new grouping would affect their behavior, and what microhabitats
      the individuals preferred within the complex habitat. Initially, all six
      individuals remained in the same enclosure without conflict. After a period of
      approximately 6 weeks, 2.1 of these individuals were removed for their safety,
      due to increasingly aggressive interactions. The data we collected indicate that
      the species may have an exploded lek type of mating system in the wild and that
      individuals may flock together in the nonbreeding season. In addition, males and
      females seem to prefer different types of shade regimes. These results suggest
      ways to improve husbandry and breeding success of the species in captivity. Zoo
      Biol 20:15-25, 2001. Copyright 2001 Wiley-Liss, Inc.

PMID- 11319778
TI  - A preliminary behavioral comparison of two captive all-male gorilla groups.
AB  - Gorillas live in polygamous harem groups, generally composed of one male, several
      adult females, and their offspring. With an equal numbers of male and female
      gorillas born in captivity, however, housing gorillas in social breeding units
      inevitably means that some males will not have access to female social partners.
      Thus, the future of the captive gorilla population depends on the collective
      ability of zoos to house equal numbers of males and females. This study examined
      the behavioral profiles of two all-male groups of captive lowland gorillas
      (Gorilla gorilla gorilla) to provide information on this type of housing
      situation. One group consisted of three subadult individuals, while the other
      consisted of two subadults and a silverback. Data were collected during two 6
      month intervals, for a total of 284 hr. The behavioral profiles of the animals
      were stable over the course of the study but proximity patterns changed.
      Differences in feeding, solitary play, and object-directed behavior were found
      between groups, while no significant differences were observed in affiliative or
      agonistic social behavior. At both institutions, group cohesion appeared to be
      high, particularly between subadults; these individuals spent approximately 10%
      of their time engaging in social behavior and 25-50% of their time in close
      proximity (within 5 m). However, the Zoo Atlanta males spent significantly more
      time within 1 m and 5 m of each other than the Santa Barbara males, which may
      reflect a higher level of cohesiveness among members of the Zoo Atlanta group.
      The behavioral profiles of the animals in this study were similar to those found
      in bachelor groups of wild mountain gorillas. One notable exception was the
      absence of homosexual behavior between the silverback and subadults in Santa
      Barbara and the low frequency of this behavior between subadults in both groups.
      Although more longitudinal data are needed, these data suggest that all-male
      groups can be a feasible housing strategy for males at certain periods of their
      life span. Zoo Biol 20:27-40, 2001. Copyright 2001 Wiley-Liss, Inc.

PMID- 11319779
TI  - Application of a noninvasive, PCR-based test for sex identification in an
      endangered parrot, Amazona guildingii.
AB  - The St. Vincent Amazon Parrot Consortium was established during the 1980s in an
      effort to cooperatively manage the captive population of the St. Vincent parrot
      (Amazona guildingii) and support conservation of the wild population. Ex situ
      management of A. guildingii has been hindered by the sexual monomorphism of the
      group, mediated in the past through the use of time-consuming, expert-driven, and
      sometimes hazardous sexing procedures. In this article, we apply a noninvasive,
      molecular sexing technique, using the polymerase chain reaction (PCR) and DNA
      from a single feather tip to the captive populations of A. guildingii residing on
      St. Vincent (66 individuals) and Barbados (13 individuals). This study allowed
      for the rapid assessment of gender, while posing no threat to individual health,
      and will facilitate the efforts of the consortium breeding programs in the United
      States, Europe and on the islands of St. Vincent and Barbados. Zoo Biol 20:41-45,
      2001. Copyright 2001 Wiley-Liss, Inc.

PMID- 11319780
TI  - Comparisons among selected neonatal biomedical parameters of four species of semi
      free ranging Hippotragini: Addax (Addax nasomaculatus), scimitar-horned oryx
      (Oryx dammah), Arabian oryx (Oryx leucoryx), and sable antelope (Hippotragus
      niger).
AB  - Basic biomedical data from 164 neonates of four species of the tribe
      Hippotragini, addax (Addax nasomaculatus), scimitar-horned oryx (Oryx dammah),
      Arabian oryx (Oryx leucoryx), and sable antelope (Hippotragus niger), were
      compared at one zoological institution over a 9-year period. Measured biomedical
      parameters included body weight, temperature, pulse and respiratory rates, packed
      cell volume (PCV), total plasma protein, glucose, IgG assessment via zinc sulfate
      turbidity, and white blood cell count with differential. All species were
      maintained in a semi-free ranging setting with the same diet, available shelter,
      and opportunity for social interaction. Based on clinical and field observations,
      all neonates used in the study were believed to be at least 24 hr old, to have
      bonded with the dam, and to have no obvious physical abnormalities. Median body
      weights were similar only in the addax and Arabian oryx with sable antelope
      having the largest median body weight. No significant differences in rectal
      temperatures or pulse rates were found among species. Median respiratory rates
      were similar between certain groups. Arabian oryx and scimitar-horned oryx shared
      the highest packed cell volumes while the sable antelope had the lowest. Sable
      antelope had the highest median total plasma protein with no significant
      differences among the other species. Sable were also significantly lower in
      median blood glucose than the three other Hippotraginae. Zinc sulfate turbidities
      in all species were similar. Addax had higher median total white blood cell
      counts than sable. No significant differences in the median numbers of segmented
      neutrophils, band neutrophils, and eosinophils were detected among species.
      Basophils were only found in the scimitar-horned oryx in one animal. Addax had
      higher median lymphocyte counts than sable and Arabian oryx as well as higher
      median monocyte counts than sable. All four species exhibited higher median
      counts of neutrophils compared with lymphocytes. The biomedical differences
      observed highlight the importance of having an accurate database of clinical
      normal values against which to evaluate neonatal health. Zoo Biol 20:47-54, 2001.
      Copyright 2001 Wiley-Liss, Inc.

PMID- 11319781
TI  - Is peak height sufficient?
AB  - The suggestion that more power can be obtained from a genome scan by
      consideration of "peak width" in addition to "peak height" has been
      controversial. Regarding this question from the viewpoint of smoothing, one finds
      that to the extent that smoothing increases the informativeness of individual
      markers it is possible to obtain increased power; but for markers that are fully
      informative the value of smoothing is questionable.

PMID- 11319782
TI  - True and false positive peaks in genomewide scans: The long and the short of it.
AB  - When performing a genome scan in linkage or linkage disequilibrium studies to
      detect loci underlying complex or quantitative traits, it is important to attempt
      to distinguish between true and false positives using the appropriate statistical
      methods. There has been some controversy in the literature regarding the use of
      the length of a positive peak, i.e., the length of a chromosome region displaying
      identity-by-descent in linkage studies among affected individuals or the length
      of a continuous chromosome region for which the test statistic is above a certain
      threshold. We show in this study, by reasoning and by simulation studies, that
      conditional on the strength of evidence for a locus affecting a trait of
      interest, i.e., conditional on the peak height of a test statistic, there is no
      information in the length of the peak. Our finding has implications for linkage
      and association studies.

PMID- 11319783
TI  - Power and robustness of a score test for linkage analysis of quantitative traits
      using identity by descent data on sib pairs.
AB  - Identification of genes involved in complex traits by traditional (lod score)
      linkage analysis is difficult due to many complicating factors. An unfortunate
      drawback of non-parametric procedures in general, though, is their low power to
      detect genetic effects. Recently, Dudoit and Speed [2000] proposed using a
      (likelihood-based) score test for detecting linkage with IBD data on sib pairs.
      This method uses the likelihood for theta, the recombination fraction between a
      trait locus and a marker locus, conditional on the phenotypes of the two sibs to
      test the null hypothesis of no linkage (theta = (1/2)). Although a genetic model
      must be specified, the approach offers several advantages. This paper presents
      results of simulation studies characterizing the power and robustness properties
      of this score test for linkage, and compares the power of the test to the Haseman
      Elston and modified Haseman-Elston tests. The score test is seen to have
      impressively high power across a broad range of true and assumed models,
      particularly under multiple ascertainment. Assuming an additive model with a
      moderate allele frequency, in the range of p = 0.2 to 0.5, along with
      heritability H = 0.3 and a moderate residual correlation rho = 0.2 resulted in a
      very good overall performance across a wide range of trait-generating models.
      Generally, our results indicate that this score test for linkage offers a high
      degree of protection against wrong assumptions due to its strong robustness when
      used with the recommended additive model.

PMID- 11319784
TI  - Issues concerning association studies for fine mapping a susceptibility gene for
      a complex disease.
AB  - The usefulness of association studies for fine mapping loci with common
      susceptibility alleles for complex genetic diseases in outbred populations is
      unclear. We investigate this issue for a battery of tightly linked anonymous
      genetic markers spanning a candidate region centered around a disease locus, and
      study the joint behavior of chi-square statistics used to discover and to
      localize the disease locus. We used simulation methods based on a coalescent
      process with mutation, recombination, and genetic drift to examine the spatial
      distribution of markers with large noncentrality parameters in a case-control
      study design. Simulations with a disease allele at intermediate frequency,
      presumably representing an old mutation, tend to exhibit the largest
      noncentrality parameter values at markers near the disease locus. In contrast,
      simulations with a disease allele at low frequency, presumably representing a
      young mutation, often exhibit the largest noncentrality parameter values at
      markers scattered over the candidate region. In the former cases, sample sizes or
      marker densities sufficient to detect association are likely to lead to useful
      localization, whereas, in the latter case, localization of the disease locus
      within the candidate region is much less likely, regardless of the sample size or
      density of the map. The effects of increasing sample size or marker density are
      also investigated. Based upon a single marker analysis, we find that a simple
      strategy of choosing the marker with the smallest associated P value to begin a
      laboratory search for the disease locus performs adequately for a common disease
      allele. We also investigated a strategy of pooling nearby sites to form multiple
      allele markers. Using multiple degree of freedom chi-square tests for two or
      three nearby sites, we found no clear advantage of this form of pooling over a
      single marker analysis. Genet. Epidemiol. 20:432-457, 2001. Published by Wiley
      Liss, 2001.

PMID- 11319785
TI  - Evidence for a major gene influence on abdominal fat distribution: the Minnesota
      Breast Cancer Family Study.
AB  - Abdominal fat has been shown to be an important risk factor for many chronic
      conditions, including diabetes, heart disease, and breast cancer. The objective
      of this study was to provide evidence for a major gene influence on the ratio of
      waist to hip circumference (WHR), a measurement commonly used in large scale
      studies to indicate the presence of abdominal fat. Segregation analysis was
      conducted on three subsets of families from the Minnesota Breast Cancer Family
      Study. One analysis was conducted among families with WHR measurements on all
      women. Two additional analyses were conducted on subsets of women stratified on
      menopausal status. Multiple regression analysis was used to identify factors
      associated with WHR expressed as a continuous trait. Complex segregation analyses
      were performed on the continuous trait of WHR and the covariates identified in
      the regression analysis. In the analysis of all women, all hypotheses were
      rejected. Among premenopausal women, the environmental hypothesis with no
      heterogeneity between generations fit the data best (P = 0.85). However, among
      postmenopausal women, the requirements for conclusion of the presence of a major
      gene were met. All non-Mendelian hypotheses were rejected (P < 0.0001), but the
      additive hypothesis was not rejected (P = 0.19) and provided the best fit to the
      data. The putative major gene identified by this model accounted for 42% of total
      phenotypic variance in WHR among these postmenopausal women. The allele for high
      WHR had a frequency of 27%. These findings support the hypothesis that the
      distribution of abdominal fat in postmenopausal women is under genetic control.

PMID- 11319786
TI  - Accurate mass measurement of synthetic analogues of prazosine by matrix-assisted
      laser desorption/ionisation time-of-flight mass spectrometry.
AB  - Matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry
      (MALDI-TOFMS) has been investigated as a tool for accurate determination of the
      molecular mass of synthetic analogues of prazosine, a molecule used for the
      treatment of hypertension. Samples were dissolved in methanol, mixed with mass
      calibration standards, and crystallised on the target with alpha-cyano-4
      hydroxycinnamic acid as matrix. Acquisition of spectra was rapidly completed in
      reflectron mode, allowing high resolution (6000-10000) and sensitive (about 1-10
      pmol of sample on target) determination of the synthetic products. The results
      show the effectiveness of MALDI-TOFMS for accurate mass determination of these
      fairly large molecules, which are otherwise difficult to analyse by other high
      resolution mass spectrometric techniques.

PMID- 11319787
TI  - Quantitative determination of noncovalently bound acridinium in protein
      conjugates by liquid chromatography/electrospray ion trap mass spectrometry.
AB  - A sensitive and robust liquid chromatography/electrospray ion trap mass
      spectrometry (LC/MS/MS) method has been developed for the quantitative
      determination of noncovalently bound acridinium free acid in protein-acridinium
      conjugates. The lower level of quantitation (LOQ) for acridinium free acid was
      determined to be 0.6 ng. The assay was validated with a linear concentration
      range of 0.6-60 ng. The method requires minimum sample handling and is specific,
      reproducible, and provides a new aspect for protein-acridinium conjugate
      characterization.

PMID- 11319788
TI  - Copper(I) chloride: a simple salt for enhancement of polystyrene cationization in
      matrix-assisted laser desorption/ionization mass spectrometry.
AB  - The possibility of using copper(I) chloride as a doping salt to enhance the
      cationization of polystyrene in matrix-assisted laser desorption/ionization mass
      spectrometry (MALDI-MS) was investigated. It was shown that copper(I) chloride
      possesses sufficient solubility in tetrahydrofuran. The parameters of the MALDI
      mass spectra of different polystyrene samples, such as the number-average (M(n))
      and mass-average (M(w)) molecular mass values, obtained by copper(I)
      cationization were compared with those obtained by means of silver(I)
      cationization, and good agreement was found. It was also shown that application
      of copper(I) chloride as a doping salt, and dithranol as a matrix, ensured good
      MALDI mass spectra of the sample spots even after storage for 1 month.

PMID- 11319789
TI  - Evaluation of axial DC offsets during scanning of a quadrupole ion trap for
      sensitivity improvements.
AB  - In the normal operation of quadrupole ion trap mass spectrometers, approximately
      half of the trapped ions are ejected through the source endcap during a mass
      selective instability scan. This reduces the sensitivity of the instrument by
      approximately 50%. In this preliminary study, a circuit was constructed that
      produced a dipolar DC offset on the axial modulation waveform to recover this
      lost ion current. A variable (0 to 10 V DC), positive and negative offset was
      applied to the source and detector endcap, respectively. This DC offset axially
      displaced the ion cloud toward the detector endcap increasing the probability of
      detection. Several compounds, including 11 pesticides, were evaluated.
      Sensitivity enhancements ranged from 13 to 97% (theoretical 100%). No spectral
      resolution problems were observed; however, a compound-dependent mass
      discrimination was observed in several cases. This mass discrimination problem is
      currently under investigation.

PMID- 11319790
TI  - Studies on the association of 2-thiazolidinecarboxylic acid and antimony
      potassium tartrate: chiral recognition and prediction of absolute configuration
      by electrospray ionization mass spectrometry.
AB  - Optically active 2-thiazolidinecarboxylic acid (2-THC), a substrate for D-amino
      acid oxidase in animal kidney, is known to undergo racemization quickly in
      solution. The association of (+)- and (-)-2-THC with antimony potassium tartrate
      K(2)[Sb(2)(L or D-tart)(2)] was studied by electrospray ionization mass
      spectrometry (ESI-MS). We observed that relative intensities of associated ions
      in acetonitrile/water solution were changing as the racemization progressed. For
      [Sb(2)(L-tart)(2)](2-), the intensities of the associated ions increased as (+)-2
      THC underwent racemization to a (-)-isomer; on the other hand, the intensity of
      the associated ion decreased as (-)-2-THC underwent racemization to a (+)-isomer.
      In the case of [Sb(2)(D-tart)(2)](2-), an opposite effect on the intensities of
      the associated ions was observed. The change in the intensities of associated
      ions can be used for chiral recognition of (+)-2-THC and (-)-2THC. Stereochemical
      models of the association of the optical isomers with [Sb(2)(L- or D-tart)(2)](2
      ) were constructed from the consideration of both hydrogen bonding of NH-O
      functions and HSAB (hard and soft acids and bases) interaction of S and Sb atoms.
      Comparison of the stereochemical models with the ESI-MS results enabled us to
      predict the absolute configurations of the 2-THC isomers.

PMID- 11319791
TI  - Investigation of hexabromocyclododecane thermal degradation pathways by gas
      chromatography/mass spectrometry.
AB  - The decomposition products of hexabromocyclododecane (HBCD), a widely used
      brominated flame retardant, were investigated by gas chromatography/mass
      spectrometry (GC/MS). HBCD thermal degradation was conducted under a moderate
      heating rate (10 degrees C/min) in a batch reactor using both inert and oxidizing
      atmospheres. GC/MS analysis allowed the identification of substances derived from
      the primary pyrolysis process at the moderate heating rates used. The presence of
      oxygen seems to have a negligible influence on the degradation products obtained
      in HBCD decomposition, at least at moderate heating rates. Based on the
      identified products, the main pathways of HBCD thermal degradation were assessed
      and a mechanism for HBCD decomposition was proposed. The results obtained
      indicate that hexa-, penta- and tetrabrominated polyaromatic structures seem not
      to be primary products of HBCD decomposition, and may only be obtained by
      secondary bromination reactions.

PMID- 11319792
TI  - Tandem mass spectrometric analysis of quaternary ammonium pesticides.
AB  - A detailed MS(n) study on an ion trap instrument of the quaternary ammonium
      pesticides paraquat, diquat, difenzoquat, mepiquat and chlormequat reveals a
      number of ions not reported previously, and has allowed examination of the
      fragmentation pathways. A number of transitions that are highly specific to each
      quat have been identified. Optimal ion trap operating conditions determined using
      Simplex optimisation can promote either detection of a particular fragmentation
      transition or a range of MS/MS product ions with a high overall signal response.
      Thus, fragmentation conditions were optimised to enhance the specificity or
      sensitivity of MS/MS methods.

PMID- 11319793
TI  - Preparation and mass spectrometric study of egg yolk antibody (IgY) against
      rabies virus.
AB  - Rabies virus was used as the antigen to immunize laying chickens. Anti-rabies
      virus immunoglobulin Y(IgY) was isolated from yolks of the eggs laid by these
      chickens using a two-step salt precipitation and one-step gel filtration
      protocol. The purified IgY was reduced with dithiothreitol, and heavy chains (HC)
      and light chains (LC) were obtained. In addition, the purified IgY was digested
      with pepsin and the fragment with specific antigen binding properties (Fab) was
      produced. Using matrix-assisted laser desorption/ionization mass spectrometry
      (MALDI-TOFMS), the average molecular weights of IgY, HC, LC, and Fab were
      determined as 167 250, 65 105, 18 660, and 45,359 Da, respectively. IgY has two
      structural differences compared with mammalian IgGs. First, the molecular weight
      of the heavy chain of IgY is larger than that of its mammalian counterpart, while
      the molecular weight of the light chain of IgY is smaller. Second, upon pepsin
      digestion, anti-rabies virus IgY is degraded into Fab, in contrast to mammalian
      IgG, which has been reported to be degraded into F(ab')(2) under the same
      conditions.

PMID- 11319794
TI  - Gln-Gly cleavage: a dominant dissociation site in the fragmentation of protonated
      peptides.
AB  - An understanding of the gas-phase dissociation of protonated peptides within the
      mass spectrometer is essential for automated high-throughput protein
      identification. In this communication we describe a facile cleavage of the Gln
      Gly peptide bond under low-collisional energy conditions. A variety of synthetic
      peptides have been analysed where key amino acids have been substituted within
      the sequence PQGPPQQGGR, which is a consensus repeat present in the tryptic
      peptides of acidic proline-rich protein 1 (PRP-1). The collision-induced
      dissociation spectra obtained from the PRP-1 tryptic peptides and the synthetic
      peptides indicate that facile Gln-Gly cleavage occurs when an X-Gln-Gly-Y
      sequence is present in a peptide, where X is any amino acid and Y any amino acid
      other than Gly.

PMID- 11319795
TI  - Electron impact mass spectral interpretation for some thiophosphoryl-p
      acetylaminobenzenesulfonamides.
AB  - This work discusses the synthesis and the fragmentation patterns for 2-(p
      acetylaminosulfonamido)-2-thiono-(5,5-dimethyl-1,3,2-dioxaphosphorinane)(1) and
      for the p-acetylaminosulfonylamides of O,O-diethylthiophosphoric acid (2), O,O
      diphenylthiophosphoric acid (3), dimethylaminocyclohexylthiophosphoric acid (4),
      and diethylaminophenylthiophosphoric acid (5). A thionamidic-thiolimidic
      structure was attributed to compounds 1-5, consistent with their IR and NMR
      spectra. EI mass spectra at 70 eV, high resolution (HR) mass measurements and
      metastable ion spectra were used to elucidate the fragmentation processes and to
      determine the kinetic energy release values associated with the metastable ion
      dissociations. HR accurate mass measurements were used to confirm the
      compositions of the more abundant ions.

PMID- 11319796
TI  - Practical and theoretical considerations in the gas
      chromatography/combustion/isotope ratio mass spectrometry delta(13)C analysis of
      small polyfunctional compounds.
AB  - Carbohydrates and proteins are among the most abundant naturally occurring
      biomolecules and so suitable methods for their reliable stable isotope analysis
      by gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS) are
      required. Due to the non-volatile nature of these compounds they require
      hydrolytic cleavage to their lower molecular weight subunits and derivatisation
      prior to GC/C/IRMS analysis. The addition of carbon to the molecules and any
      kinetic isotopic fractionation associated with derivatisation must be accounted
      for in order to provide meaningful stable isotope values and estimates of
      propagated errors. To illustrate these points amino acid
      trifluoroacetate/isopropyl esters and alditol acetates were prepared from
      authentic amino acids and monosaccharides, respectively. As predicted from the
      derivatisation reaction mechanisms, a kinetic isotope effect was observed which
      precludes direct calculation of delta(13)C values of the amino acids and
      monosaccharides by simple mass balance equations. This study shows that the
      kinetic isotope effect associated with derivatisation is both reproducible and
      robust, thereby allowing the use of correction factors. We show how correction
      factors can be determined and accurately account for the addition of derivative
      carbon. As a consequence of the addition of a molar excess of carbon and the
      existence of a kinetic isotope effect during derivatisation, errors associated
      with determined delta(13)C values must be assessed. We illustrate how such errors
      can be quantified (for monosaccharides +/-1.3 per thousand and for amino acids
      between +/-0.8 per thousand and +/-1.4 per thousand). With the magnitude of the
      errors for a given delta(13)C value of a monosaccharide or amino acid quantified,
      it is possible to make reliable interpretations of delta(13)C values, thereby
      validating the determination of delta(13)C values of amino acids as TFA/IP esters
      and monosaccharides as alditol acetates.

PMID- 11319797
TI  - Different expression of P14ARF defines two groups of breast carcinomas in terms
      of TP73 expression and TP53 mutational status.
AB  - In 95 breast carcinomas, we investigated P14ARF and TP73 mRNA expression and
      their relationship to TP53 mutations, determined by an immunohistochemical
      method, studying several clinicopathologic features of the tumors. P14ARF and
      TP73 mRNA levels were determined by semiquantitative reverse transcription
      polymerase chain reaction (RT-PCR), using beta-actin as a control. P14ARF was
      overexpressed in 19% of the cases and underexpressed in 24%. TP73 was
      overexpressed in 22% of the tumors, and normal levels were found in the remaining
      78%. The analysis of TP53 showed positive immunostaining in 38% of cases. The
      association of P14ARF and TP73 overexpression was statistically significant, as
      was the association between positive TP53 staining and TP73 overexpression.
      P14ARF was related to TP53 only in those cases in which there was low expression
      of P14ARF. Concomitant overexpression of P14ARF and TP73 was statistically
      related to positive TP53 immunostaining. The analysis of concomitant P14ARF and
      TP73 overexpression and clinicopathologic parameters of the tumors showed a
      statistically significant difference with respect to peritumoral vessel invasion
      (P = 0.01), lymph node metastasis (P = 0.03), negative ERBB2 expression (P =
      0.005), and more advanced pathologic stages (P = 0.03). These results suggest
      that overexpression of P14ARF and TP73 could be implicated in breast carcinoma
      tumorigenesis and, ultimately, in the phenotypic features of these lesions.

PMID- 11319798
TI  - Haplotype analysis and age estimation of the 113insR CDKN2A founder mutation in
      Swedish melanoma families.
AB  - Germline mutations in the CDKN2A tumor suppressor gene located on 9p21 have been
      linked to development of melanomas in some families. A germline 3-bp insertion in
      exon 2 of CDKN2A, leading to an extra arginine at codon 113 (113insR), has been
      identified in 17 Swedish melanoma families. Analysis of 10 microsatellite
      markers, spanning approximately 1 Mbp in the 9p21 region, showed that all
      families share a common allele for at least one of the markers closest to the
      CDKN2A gene, suggesting that the 113insR mutation is an ancestral founder
      mutation. Differences in the segregating haplotypes, due to meiotic
      recombinations and/or mutations in the short-tandem-repeat markers, were analyzed
      further to estimate the age of the mutation. Statistical analysis using a maximum
      likelihood approach indicated that the mutation arose 98 generations (90%
      confidence interval: 52-167 generations), or approximately 2,000 years, ago.
      Thus, 113insR would be expected to have a more widespread geographic distribution
      in European and North American regions with ancestral connections to Sweden.
      Alternatively, CDKN2A may lie in a recombination hot spot region, as suggested by
      the many meiotic recombinations in this narrow approximately 1-cM region on 9p21.

PMID- 11319799
TI  - Genomic alterations in uterine leiomyosarcomas: potential markers for clinical
      diagnosis and prognosis.
AB  - Genomic alterations were analyzed in 21 uterine leiomyosarcomas (ULMSs) by
      comparative genomic hybridization. DNA copy number changes were detected in all
      21 tumors. The most frequent losses were 13q (16/21 = 76%), 10q (13/21 = 62%),
      16q (8/21 = 38%), 12p (7/21 = 33%), and 2p (9/21 = 43%). The most common gains
      were 17p (8/21 = 38%), Xp (7/21 = 33%), and 1q (7/21 = 33%). High-copy-number
      gains (ratio > 1.5) were identified in Xp, 1q, and 17p. Loss of 13q was
      identified in both low-grade and high-grade tumors. Inactivation of a tumor
      suppressor gene in 13q may be an early event in the development of
      leiomyosarcomas. Loss of 10q, 2p, and 12p and gains of 1q as well as 17p were
      frequently found in high-grade tumors and recurrent tumors. Inactivation of tumor
      suppressor genes and activation of oncogenes in these regions may be associated
      with a more aggressive behavior of ULMS. Patients with only loss of 13q and
      without the other alterations listed above had longer survival times. Gains of
      Xp, 17p, and 1q and losses of 13q, 10q, 16q, 12p, and 2p have been reported in
      extra-uterine leiomyosarcomas. Our findings indicate that the pathogenesis of
      uterine leiomyosarcomas and extra-uterine leiomyosarcomas follows the same
      genetic pathways.

PMID- 11319800
TI  - Identification of recurrent chromosomal rearrangements and the unique
      relationship between low-level amplification and translocation in glioblastoma.
AB  - To elucidate the structural abnormalities and the relationship between chromosome
      structural disorders and DNA copy number aberrations in tumor cells, we applied
      the techniques of spectral karyotyping (SKY), comparative genomic hybridization
      (CGH), and fluorescence in situ hybridization (FISH), using yeast artificial
      chromosome (YAC) probes for nine human glioblastoma cell lines. One striking
      finding was that independently derived cell lines had the same recurrent marker
      chromosomes. Seven recurrent chromosomes were detected by these cytogenetic
      methods. In particular, cell lines U251, SNB-19, and U373-MG showed very similar
      karyotypes. It is also interesting that regions of DNA amplification were found
      translocated and/or inserted at a high rate (91.7%). In all, there were 12
      amplified loci in five of the nine cell lines. These amplified chromosomal bands
      were scattered on the chromosomes, including the normal chromosome, with one
      exception (7q32-qter in U373-MG). FISH with YAC clones mapping to these
      chromosomal regions as DNA probes often showed DNA probe signals not only at
      original chromosomal sites but also in translocated or inserted segments. This
      form of DNA amplification was characterized by low-level increases (four- to 10
      fold) and by translocation or insertion of the relevant chromosomal locus. These
      studies shed light on typical derivative chromosomes and the relationship between
      DNA amplification and chromosomal translocation in glioblastoma.

PMID- 11319801
TI  - Identification of new translocations involving ETV6 in hematologic malignancies
      by fluorescence in situ hybridization and spectral karyotyping.
AB  - TEL/ETV6 is the first transcription factor identified that is specifically
      required for hematopoiesis within the bone marrow. This gene has been found to
      have multiple fusion partners; 35 different chromosome bands have been involved
      in ETV6 translocations, of which 13 have been cloned. To identify additional ETV6
      partner genes and to characterize the chromosomal abnormalities more fully, we
      studied bone marrow samples from patients known to have rearrangements of 12p,
      using fluorescence in situ hybridization (FISH) and spectral karyotyping (SKY).
      FISH analysis was done with 14 probes located on 12p12.1 to 12p13.3. Nine ETV6
      rearrangements were identified using FISH. The aberrations include
      t(1;12)(p36;p13), t(4;12)(q12;p13) (two patients), t(4;12)(q22;p13),
      t(6;12)(p21;p13), der(6)t(6;21)(q15;q?)t(12;21)(p13;q22), t(6;12)(q25;p13),
      inv(12)(p13q24), and t(2;2;5;12;17)(p25;q23;q31;p13;q12). Six new ETV6 partner
      bands were identified: 1p36, 4q22, 6p21, 6q25, 12q24, and 17q12. Our present data
      as well previous data from us and from other researchers suggest that ETV6 is
      involved in 41 translocations. The breakpoints in ETV6 were upstream from the
      exons coding for the HLH (helix-loop-helix) domain in six cases. Although
      cytogenetic analysis identified 12p abnormalities in all cases, FISH and SKY
      detected new and unexpected chromosomal rearrangements in many of them. Thus,
      complete characterization of the samples was achieved by using all three
      techniques in combination.

PMID- 11319802
TI  - Suppression of tumorigenicity in the human prostate cancer cell line M12 via
      microcell-mediated restoration of chromosome 19.
AB  - Previously we immortalized human, nontransformed prostate epithelial cells with
      SV40 large T-antigen (SV40TAg) and derived increasingly aggressive sublines from
      the immortalized line. The progression of the tumorigenic sublines to metastatic
      capacity was accompanied by the formation of an unbalanced translocation between
      chromosomes 16 and 19, resulting in loss of 19p and proximal 19q. To test whether
      the tumorigenic and/or metastatic phenotype was causally related to this genetic
      alteration, we restored a neo-tagged human chromosome 19 to M12 cells by
      microcell-mediated transfer and assessed their growth. In vitro, the resultant
      hybrids grew more slowly in monolayer culture and showed a significant reduction
      in anchorage-independent growth as compared to M12neo controls. In vivo, all mice
      (13/13) injected subcutaneously (SC) with control M12neo cells developed tumors
      after 9-15 days. In contrast, 9/15 mice injected SC with microcell-transferred
      chromosome 19 hybrid cells failed to form tumors, with 6/15 producing very small
      tumors after 120 days. Analysis of three of these six tumors showed consistent,
      new chromosomal changes. Furthermore, in one of the tumors, loss of a chromosome
      19 was noted in 40% of the cells. After intraprostatic injections of the hybrid
      cells, only 2/7 mice developed microscopic tumors, with no metastases. These data
      suggest the presence of a gene or genes on chromosome 19 that function to
      suppress growth.

PMID- 11319803
TI  - Multivariate analyses of genomic imbalances in solid tumors reveal distinct and
      converging pathways of karyotypic evolution.
AB  - A total of 3,016 malignant solid tumors (kidney, colorectal, breast, head and
      neck, ovarian, and lung carcinomas, neuroglial tumors, malignant melanoma, and
      testicular germ cell tumors) were selected for statistical analyses regarding
      karyotypic evolution. Genomic imbalances, i.e., net gains and losses, present in
      more than 5% of each tumor type were identified. Individual tumors were then
      classified with respect to absence or presence of these imbalances. To analyze
      for possible patterns of correlated imbalances, principal component analyses
      (PCA) were performed. Furthermore, algorithms were developed to analyze the
      temporal order of the imbalances, as well as the possible selection for early or
      late appearance in the karyotypic evolution. By analyzing the temporal order of
      imbalances common to many tumor types, a general order for nine of these emerged,
      namely, +7, -3p, -6q, -1p, -8p, -17p, -9p, -18, and -22. The distributions of the
      number of imbalances per case revealed a geometrical distribution, ranging from
      one to nine imbalances per tumor, in the majority of the tumor types. In tumor
      types in which cases with a high number of imbalances per case were frequent,
      notably head and neck, ovarian, and lung carcinomas, the overall distributions
      were bimodal, indicating the presence of two modes of chromosome evolution. By
      combining data from the PCA with the temporal analyses, it was possible to
      identify karyotypic pathways. It was found that the majority of the tumor types
      displayed more than one cytogenetic route, but, as the karyotypic evolution
      continued, these converged to a common pathway.

PMID- 11319804
TI  - Three chromosomal rearrangements in neuroblastoma cluster within a 300-kb region
      on 1p36.1.
AB  - Deletions in the short arm of chromosome 1 (1p36) and MYCN amplification are
      common in neuroblastoma. Previously we showed evidence of at least two different
      neuroblastoma tumor-suppressor loci on 1p. One is associated with MYCN single
      copy tumors and maps distal on 1p36.3. A second, more proximal locus maps to
      1p36.1 and is deleted in about 90% of neuroblastomas with MYCN amplification. The
      cell line UHG-NP has the smallest 1p36 deletion of all neuroblastoma cell lines
      with MYCN amplifications. We assume that the more proximal locus maps within this
      deletion, close to its proximal border. Here we present the exact localization of
      the 1p deletion breakpoint of UHG-NP. A 600-kb PAC contig spanning the breakpoint
      was analyzed for genes and aberrations. Two more neuroblastoma-associated
      aberrations were mapped within 150 kb of the UHG-NP breakpoint. Within the
      contig, we identified nine genes expressed in neuroblastoma cells. One of these
      genes, AML2, maps 200 kb distal to the UHG-NP breakpoint but is expressed only
      rarely in neuroblastoma and showed no mutations.

PMID- 11319805
TI  - Spectral karyotyping reveals 17;22 fusions in a cytogenetically atypical
      dermatofibrosarcoma protuberans with a large marker chromosome as a sole
      abnormality.
AB  - The presence of an extra ring chromosome containing material from 17q and 22q,
      or, less frequently, a t(17;22)(q22;q13), is a cytogenetic hallmark of
      dermatofibrosarcoma protuberans (DFSP). However, occasionally tumors with other,
      atypical karyotypes are encountered. We describe a case of recurrent DFSP without
      a ring chromosome or a t(17;22) on standard cytogenetic analysis. In all cells
      analyzed by G-banding, an additional, large marker chromosome was present as a
      sole abnormality. This chromosome apparently included chromosome 8 or the 8q arm,
      but the origin of its remaining part could not be determined with certainty. To
      characterize further the abnormal chromosome, we applied spectral karyotyping
      (SKY). SKY confirmed the presence of an extra chromosome 8 or arm 8q in the
      marker and showed that its remaining part was composed of segments from
      chromosomes 7, 17, 21, and 22, with two copies of a 17;22 fusion. Our results and
      the literature data suggest that, in addition to a specific 17;22 fusion,
      amplification of material from chromosomes 17, 22, 8, 5, 7, and 21 may play a
      role in DFSP development and/or progression. Furthermore, our case demonstrates
      the usefulness of SKY in detection of a diagnostically relevant 17;22 fusion in
      DFSP patients who have unusual karyotypic features.

PMID- 11319807
TI  - Alteration of chromosome arm 6p is characteristic of primary mediastinal B-cell
      lymphoma, as identified by genome-wide allelotyping.
AB  - Five cases of primary mediastinal B-cell lymphoma (PMBL) each have been studied
      with 375 microsatellite markers from all 22 autosomes. Of the 151 genomic
      alterations among the 1,875 assays, only five were allelic losses. The remainder
      of the microsatellite alterations consisted of 114 allelic imbalances and 32
      instabilities. Microsatellite alterations were found in all cases on chromosomal
      arms 6p and 9p. These allelic imbalances most likely are indicative of genetic
      amplification, a finding agreeing well with those of studies using either
      comparative genomic hybridization or arbitrarily primed polymerase chain
      reaction, in which amplification of chromosome arm 9p in PMBL has been found. The
      allelic imbalances on chromosome arm 6p always included marker D6S276 located at
      6p21.3-p22.3, where the MHC class I genes reside. These allelic imbalances may be
      reflective of alterations in the expression of the MHC gene products,
      characteristic of PMBL. Allelic anomalies close to the MYB gene locus on 6q were
      detected in two cases and prompted the analysis of MYB rearrangements in a series
      of 30 lymphomas. One rearrangement was detected in one of 18 cases of PMBL and in
      none of 10 diffuse, large B-cell lymphomas and two T-cell lymphomas. Our genome
      wide microsatellite analysis provides independent confirmation that PMBL is
      characterized by infrequent chromosomal losses and by frequent genetic
      alterations involving chromosomal arm 9p. For the first time, chromosomal arm 6p
      has been identified as a highly frequent target of genetic alterations in this
      tumor type. Finally, MYB may also be involved occasionally in PMBL pathogenesis.

PMID- 11319806
TI  - Coduplication of the MLL and FLT3 genes in patients with acute myeloid leukemia.
AB  - Tandem duplication (TD) of the MLL or FLT3 gene in acute myeloid leukemia (AML)
      has been reported. We examined whether TD of these two genes occurs
      simultaneously. We analyzed 13 AML and 2 myelodysplastic syndrome patients,
      including 6 adult patients with trisomy 11 and 9 pediatric patients with TD of
      the FLT3 gene, using RT-PCR followed by sequencing. Among these, TD of the MLL
      and FLT3 genes was found in 5 and 10 patients, respectively. Notably, TD of both
      the MLL and FLT3 genes (coduplication) was detected in two AML patients, who died
      6 and 14 months after diagnosis. TD of these two genes in AML is rare; thus,
      coduplication of these genes in the same patient is predicted to be very rare.
      Although the mechanisms of TD of both genes are different, development of TD of
      both genes may be related to an unknown similar etiology in leukemia because the
      frequency of coduplication of these genes in a single patient is considered to be
      very low. Further studies of the coduplication of these genes in AML patients may
      lead to the clarification of its mechanism and clinical implications.

PMID- 11319808
TI  - Microcell-mediated transfer of chromosome 4 into HeLa cells suppresses telomerase
      activity.
AB  - Telomerase activity can be detected in most human cancers and immortal cell
      lines. In contrast, the lack of telomerase activity in normal diploid fibroblasts
      has been correlated with progressive reduction of telomere lengths to critically
      short sizes followed by the cessation of cell division and the onset of
      senescence. Several investigators have provided evidence for the localization of
      a telomerase suppressor gene on chromosome 3. The aim of our study was to
      determine whether other chromosomes are involved in telomerase repression. Beside
      human chromosome 3 (serving as positive control), chromosomes 4, 6, and 11 were
      introduced into HeLa cells via microcell-mediated chromosome transfer. Telomerase
      activity from different hybrid cell lysates was determined at an early time point
      after fusion using a Telomerase ELISA kit. Strong repression of telomerase
      activity was only found in a subset of HeLa hybrids in which chromosome 3 or
      chromosome 4 had been introduced. Telomerase suppression induced by chromosome 3
      or 4 transfer was paralleled by a high frequency (30% or 43%, respectively) of a
      senescent-like phenotype. Chromosomes 6 and 11, the functional loss of which is
      also implicated in cervical cancer, had no effect. These results indicate that
      normal human chromosomes 3 and 4 carry a gene or genes that suppress telomerase
      activity and induce cellular senescence in HeLa cells.

PMID- 11319809
TI  - 12p12-13 deletion in prostate tumors and quantitative expression of CDKN1B and
      ETV6 candidate genes.

PMID- 11319810
TI  - Microplate enzyme-linked immunosorbent assay for the detection of primary DNA
      alterations based on the interaction with UvrA/UvrB.
AB  - An enzyme-linked microplate immunoassay for the analysis of primary DNA lesions
      is described. The assay principle is based on the interaction of the bacterial
      DNA repair proteins UvrA and UvrB with DNA and on the immunodetection of UvrB
      forming a stable complex with covalently modified nucleotides. Using this
      technique we were able to detect damages in genomic DNA induced by uv light and
      by several different genotoxic agents. The detection sensitivity of the method
      reaches down to the nanomolar range of the mutagenic compound depending on the
      type of the DNA alteration. The method might be used in automated high-throughput
      studies.

PMID- 11319811
TI  - Yeast cell permeabilization by osmotic shock allows determination of enzymatic
      activities in situ.
AB  - Yeast cells were permeabilized by incubation in 0.8 M sorbitol followed by
      suspension in dilute buffer. A preincubation with 2-mercaptoethanol was also
      included for optimal permeabilization. More than 90% of the treated cells were
      stainable with methylene blue. Determinations of cell wall-synthesizing enzymes
      (beta(1 --> 3)glucan and chitin synthases) and cytosolic enzymes in permeabilized
      cells yielded similar or higher activities than those in cell extracts. With
      chitin synthase III, the activity obtained with cells was 4- to 6-fold higher
      than in membrane preparations. Little protein leaks from the cells during
      permeabilization; yet the cells appear to be readily permeable to substrates and
      even proteins. Thus, these preparations may be of wide use for the study of
      enzymes and of biological processes in situ.

PMID- 11319812
TI  - A cell-based assay system for monitoring NF-kappaB activity in human HaCat
      transfectant cells.
AB  - A cell-based assay system for monitoring NF-kappaB activity was developed to
      determine the influence of activated NF-kappaB in human HaCaT cells. The pNF
      kappaB-SEAP-NPT plasmid that permits expression of the secretory alkaline
      phosphatase (SEAP) reporter gene in response to the NF-kappaB activity and
      contains the neomycin phosphotransferase (NPT) gene for geneticin resistance in
      host cells was constructed and transfected into the human keratinocyte cell line
      HaCaT. Human HaCaT transfectant cells were demonstrated to secrete the SEAP
      enzyme into the culture medium in a time-dependent manner until 72 h. NF-kappaB
      activities were measured by the SEAP reporter gene assay using a fluorescence
      detection method. HaCaT cell transfectants treated with antioxidants [e.g., N
      acetyl-l-cysteine and vitamin C] showed reduction of NF-kappaB activity in a time
      and concentration-dependent manner, whereas phorbol 12-myristate 13-acetate
      known as a stimulator of NF-kappaB expression increased NF-kappaB activity in a
      time- and concentration-dependent manner. This assay system could be used to
      determine the quantitative measurement of NF-kappaB activity in the human skin
      and allow the screening of anti-inflammatory agents for dermatological purpose
      from various synthetic chemicals and natural products.

PMID- 11319813
TI  - Zymography with caseogram prints: quantification of pepsinogen.
AB  - In caseogram prints, a type of zymogram which is designed for the detection of
      acid proteases, enzyme activity is detected in an overlay gel of agarose
      containing skim milk. The use of this technique for protease quantification was
      investigated in this study using pepsinogen as an example protease. The area of
      caseogram bands was found to be logarithmically related to protease activity
      whereas the intensity of the bands was no reliable measure for activity. A
      reproducible quantification procedure was described. Accuracy and variation were
      acceptable over a 128-fold range whose lower border was the detection limit (35
      pg pepsinogen).

PMID- 11319814
TI  - Application of a fluorometric assay for characterization of the catalytic
      competency of a domain III fragment of Pseudomonas aeruginosa exotoxin A.
AB  - Pseudomonas aeruginosa exotoxin A (ETA) is a member of the family of bacterial
      ADP-ribosylating toxins that use NAD(+) as the ADP-ribose donor. The reaction
      catalyzed by ETA involves the nucleophilic attack of the diphthamide residue on
      the anomeric carbon of the nicotinamide ribose forming a new glycosidic bond. A
      fluorometric assay involving the use of etheno-beta-nicotinamide adenine
      dinucleotide (epsilon-NAD(+)), an analog of NAD(+), has been found to provide a
      rapid, reliable, and sensitive procedure for assessing the kinetic parameters of
      this class of enzymes including ETA and its C-terminal fragment, PE24.
      Furthermore, application of this new assay facilitated the determination of the
      kinetic parameters for the protein substrate of ETA, elongation factor, which has
      previously been difficult to characterize. These findings provide new insights
      into catalytic mechanism of dipthamide-specific ribosyltransferases. In addition,
      this assay should also prove valuable for the study of NADases or NAD(+)
      glycohydrolase enzymes (B. Weng, W. C. Thompson, H. J. Kim, R. L. Levine, and J.
      Moss, 1999, J. Biol. Chem. 274, 31797-31803; Y. S. Cho, M. K. Han, O. S. Kwark,
      M. S. Phoe, Y. S. Cha, N. H. An, and U. H. Kim, 1998, Comp. Physiol. B: Biochem.
      Mol. Biol. 120, 175-181) and the poly-ADP-ribosyltransferases (A. A. Pieper, A.
      Verma, J. Zhang, S. H. Snyder, 1999, Trends Pharmacol. Sci. 20, 171-181; M. K.
      Jacobson and E. L. Jacobson, 1999, Trends Biochem. Sci. 24, 415-417).

PMID- 11319815
TI  - In situ assays of fungal enzymes in cells permeabilized by osmotic shock.
AB  - Permeabilization of yeast and other fungal cells by osmotic shock enabled the in
      situ assays of intracellular plasma membrane-bound enzymes, such as beta-1,3
      glucan synthase, chitin synthase, and Na(+)/K(+) ATPase as well as the soluble,
      cytoplasmic enzymes, such as lactate dehydrogenase and alpha-glucosidase. The
      permeabilization was accomplished by rapid changes in osmolarity of the washing
      buffer at 0 degrees C whereby 0.5-3.5 M glycerol, sorbitol, and/or mannitol
      and/or 1 M KCl could be used as the osmolytes. No appreciable leakage of
      intracellular proteins occurred during the permeabilization procedure. The
      described procedure caused practically complete cell permeabilization while
      avoiding treatments with organic solvents, detergents, and other xenobiotics
      currently used for the permeabilization of microbial cells.

PMID- 11319816
TI  - The ligand affinity of proteins measured by isothermal denaturation kinetics.
AB  - An isothermal denaturation kinetic method was developed for identifying potential
      ligands of proteins and measuring their affinity. The method is suitable for
      finding ligands specific toward proteins of unknown function and for large-scale
      drug screening. It consists of analyzing the kinetics of isothermal denaturation
      of the protein-with and without the presence of potential specific ligands-as
      measured by long-wavelength fluorescent dyes whose quantum yield increases when
      bound to hydrophobic regions exposed upon unfolding of the proteins. The
      experimental procedure was developed using thymidylate kinase and stromelysin as
      target proteins. The kinetics of thermal unfolding of both of these enzymes were
      consistent with a pathway of two consecutive first-order rate-limiting steps.
      Reflecting the stabilizing effect of protein/ligand complexes, the presence of
      specific ligands decreased the value of the rate constants of both steps in a
      dose-dependent manner. The dependence of the rate constants on ligand
      concentration obeyed a simple binding isotherm, the analysis of which yielded an
      accurate equilibrium constant for ligand binding. The method was validated by
      comparing its results with those obtained under the same conditions by steady
      state fluorescence spectroscopy, circular dichroism, and uv spectrophotometry:
      The corresponding rate constants were comparable for each of the analytical
      detection methods.

PMID- 11319817
TI  - Assay of protein tyrosine phosphatases by using matrix-assisted laser desorption
      ionization time-of-flight mass spectrometry.
AB  - A nonradioactive assay for protein tyrosine phosphatases (PTPs), employing a
      tyrosine-phosphorylated peptide as a substrate, has been developed and applied to
      analyze purified enzymes, cell extracts, and immunoprecipitates. The reaction was
      followed by matrix-assisted laser desorption ionization time-of-flight mass
      spectrometry (MALDI-TOF MS) in a linear and positive ion mode with delayed
      extraction. MALDI-TOF MS detects a loss of peptide mass by 80 Da as a result of
      dephosphorylation and, more importantly, it yields phospho-peptide to
      dephosphorylated product peak intensity ratios proportional to their
      concentration ratios. A strong bias of the MALDI-TOF MS toward detection of the
      non-phospho-peptide allows accurate detection of small fractions of
      dephosphorylation. The method is highly sensitive and reproducible. It can be
      applied to general assays of protein phosphatases with various phospho-peptides
      as substrates.

PMID- 11319818
TI  - Simultaneous direct determination of amiloride and triamterene in urine using
      isopotential fluorometry.
AB  - A method for the simultaneous fluorometric determination of two diuretics in
      urine is proposed. The combination of matrix isopotential synchronous
      fluorescence (MISF) and first derivative techniques provides good analytical
      results. MISF spectra are obtained by calculating the isopotential trajectory in
      the three-dimensional fluorescence spectrum for a urine solution. In the spectral
      contour, the trajectory is taken to be the portion of the line that passes by the
      fluorescence maxima of both diuretics (lambda(ex) = 365 and lambda(em) = 413 nm
      for amiloride and lambda(ex) = 365 and lambda(em) = 437 nm for triamterene).
      Because contour lines connect points of identical intensity and the trajectory is
      part of a contour line, it is called "isopotential." Analyses was carried out in
      a 1/1 (v/v) ethanol/water mixture, using an apparent pH of 6.3 provided by 0.01 M
      sodium/citrate citric acid buffer. Urine samples are diluted 50 times and provide
      linear calibration plots at amiloride and triamterene concentrations up to 320
      and 100 ng mL(-1), respectively. The goodness of the analytical signal was
      checked by using variance analysis. Signals recorded throughout the calibration
      range were subjected to three calibrations per each analyte, both in the absence
      and in the presence of variable amounts of the other analyte. Differences between
      individual calibrations and slopes were compared with those within individual
      calibrations. Based on the results, triamterene and amiloride can be accurately
      quantified in the presence of each other. The limit of detection calculated
      according to Clayton who uses error propagation throughout the calibration curve
      and a noncentralized security factor was 16.8 and 2.4 ng mL(-1) for amiloride and
      triamterene, respectively.

PMID- 11319819
TI  - Determining the binding capability of the mouse major urinary proteins using 2
      naphthol as a fluorescent probe.
AB  - The mouse major urinary proteins (MUPs) are an ensemble of isoforms secreted by
      adult male mice and involved in sexual olfactory communication. MUPs belong to
      the lipocalin superfamily, whose conserved structure is a beta-barrel made of
      eight antiparallel beta-strands forming a hydrophobic pocket that accommodates
      small organic molecules. A detailed knowledge of the molecular mechanism
      associated to the binding of those molecules can guide protein engineering to
      devise mutated proteins where the ligand specificity, binding affinity, and
      release rate can be modulated. Proteins with such peculiar properties may have
      interesting biotechnological applications for pest control, as well as in food
      and cosmetic industries. In this work, we demonstrate that the fluorescent
      molecule 2-naphthol binds to the natural ligand's binding site of MUPs with high
      affinity. In addition, we show that 2-naphthol binds to MUPs in its protonated
      form, that its fluorescence is blue-shifted, and the quantum yield is increased,
      thus confirming the high hydrophobicity of the protein pocket and the absence of
      proton acceptors inside the binding site. At large the results presented, besides
      demonstrating that the use of 2-naphthol provides a convenient and quick method
      for testing MUPs binding activity and to ascertain the quality of the protein
      preparation, suggest that MUPs can represent an interesting system for studying
      the photophysical characteristics of fluorescent molecules in a highly
      hydrophobic environment.

PMID- 11319820
TI  - Mass spectrometric analysis of cyanogen bromide fragments of integral membrane
      proteins at the picomole level: application to rhodopsin.
AB  - Advances in time-of-flight mass spectrometry allow unit mass resolution of
      proteins and peptides up to about 6000 Da molecular weight. Identification of
      larger proteins and study of their posttranslational or experimental
      modifications by mass analysis is greatly enhanced by cleavage into smaller
      fragments. Most membrane proteins are difficult to mass analyze because of their
      high hydrophobicity, typical expression in low quantities, and because the
      detergents commonly used for solubilization may be deleterious to mass analysis.
      Cleavage with cyanogen bromide is beneficial for analysis of membrane proteins
      since the methionine cleavage sites are typically located in hydrophobic domains
      and cleavage at these points reduces the size of the hydrophobic fragments.
      Cyanogen bromide also gives high cleavage yields and introduces only volatile
      contaminants. Even after cleavage membrane proteins often contain fragments that
      are difficult to chromatograph. Matrix-assisted laser desorption ionization mass
      spectrometry (MALDI MS) is capable of analyzing complex mixtures without
      chromatography. We present a MALDI MS method that quickly and reliably identifies
      the cyanogen bromide fragments and posttranslational modifications of reduced and
      alkylated bovine rhodopsin from as little as 30 pmol of rhodopsin in detergent
      solubilized retinal rod disk membranes, using 1-5 pmol of digest per sample. The
      amino acid sequences of some of the peptides in the digest were confirmed by post
      source decomposition MS analysis of the same samples. The method appears to be
      general and applicable to the analysis of membrane proteins and the protein
      composition of membrane preparations.

PMID- 11319821
TI  - Quantification of BK1-5, the stable bradykinin plasma metabolite in humans, by a
      highly accurate liquid-chromatographic tandem mass spectrometric assay.
AB  - Bradykinin is a vasoactive nonapeptide involved in cardiorenal physiology and
      inflammatory states. It has been linked to the pathophysiology of hypertension
      and diabetes. Correlating levels of bradykinin with disease states has been
      hampered by its rapid degradation, artifactual production during blood sampling,
      and nonspecific radioimmunoassay techniques. We previously identified BK1-5 as
      the stable in vivo plasma metabolite of systemic bradykinin in humans. We now
      report a sensitive and specific assay method for BK1-5 in human blood utilizing
      liquid chromatography-tandem mass spectrometry(MS) with electrospray ionization.
      [(13)C(2),(15)N]Glycine was incorporated into chemically synthesized BK1-5 for
      use as an internal standard. Blood samples (5 ml) were collected into 15-ml
      chilled ethanol to prevent artifactual kinin production and degradation. BK1-5 in
      ethanolic plasma supernatant was purified on a polymeric solid phase extraction
      cartridge. MS analysis was in the selective reaction monitoring mode. Precision
      of the assay is +/-7.5% and accuracy is 99%. Recovery of BK1-5 through sample
      preparation was 43% and the lower limit of detection is 4 fmol/ml blood.
      Concentrations of BK1-5 in 12 normal volunteers were 44.2 +/- 7.1 fmol/ml blood
      (mean +/- SE). During blood sampling, no artifactual production of BK1-5 was
      detected for up to 60 s prior to denaturing the sample. This assay provides the
      first accurate and precise method using MS to quantify BK1-5 in human blood as a
      marker for the production of systemic bradykinin in humans.

PMID- 11319822
TI  - Miniaturized amperometric biosensor based on xanthine oxidase for monitoring
      hypoxanthine in cell culture media.
AB  - Fabrication and characterization of miniaturized amperometric hypoxanthine
      biosensors are described and demonstrated for monitoring hypoxanthine in
      myocardial cell culture media. The sensors are based on xanthine oxidase (XO)
      immobilized on carbon fiber microelectrodes (CFMEs) using a composite film of
      Nafion and electropolymerized phenol (PPh). Nafion was used for XO immobilization
      because of its film hydrophobicity, enzyme-favored environment, and electrostatic
      interaction with XO, which was dispersed in Nafion film by immersing the Nafion
      coated CFMEs in XO solution for 5 h. PPh film was formed as an overlay on Nafion
      and XO-modified CFMEs via electropolymerization. Hypoxanthine was measured with
      the sensor by the oxidation of enzymatic reaction products, hydrogen peroxide
      (H(2)O(2)), and uric acid (UA) at +0.60 V (vs Ag/AgCl). The use of Nafion and PPh
      as a matrix for XO immobilization yields enhanced specificity, sensitivity, and
      linearity toward hypoxanthine. A dynamic linear range of 5.0 microM to 1.8 mM was
      achieved with a calculated detection limit of 1.5 microM (S/N = 3) and a
      sensitivity of 3.144 nA/mM. In addition, the measurement was virtually
      interference-free from easily oxidizable species such as UA, ascorbic acid,
      physiological levels of neurotransmitters, and their principal metabolites. The
      biosensor was used to monitor hypoxanthine accumulation in myocardial cell
      culture media, in which the level of extracellular hypoxanthine was found to
      increase with ischemic tolerance.

PMID- 11319823
TI  - Determination of the hydrophobicity of local anesthetic agents.
AB  - Hydrophobicity, a term used to describe a fundamental physicochemical property of
      local anesthetics, was in the past obtained by octanol/buffer partitioning. It
      has been suggested that the octanol method, despite its obvious advantages, also
      has some drawbacks. HPLC has become an attractive alternative for the measurement
      of hydrophobicity and has been applied to local anesthetics recently. However,
      the methods in current use for measuring the hydrophobicity of local anesthetics
      suffer from a number of limitations and remain obscure. This study introduces a
      new HPLC method for measuring the hydrophobicity of eight local anesthetics in
      current clinical use. Using a C(18) derivatized polystyrene-divinylbenzene
      stationary phase HPLC column, the log k'(w) values of local anesthetics were
      determined by measuring the capacity factor k'(i) in the process of
      chromatographic separation using a hydrophobic stationary phase and a hydrophilic
      mobile phase. A rapid reversed-phase HPLC method was developed to directly
      measure log k'(w) of eight local anesthetics. A high correlation between log
      k'(w) and hydrophobicity (log P(oct)) from the traditional shake-flask method was
      obtained for the local anesthetics, demonstrating the reliability of the method.
      The results reveal an improved method for measuring the hydrophobicity of the
      local anesthetic agents in the unionized form. This simple, sensitive and
      reproducible approach may serve as a valuable tool for describing the
      physicochemical properties of novel local anesthetics.

PMID- 11319824
TI  - From small-molecule reactions to protein folding: studying biochemical kinetics
      by stopped-flow electrospray mass spectrometry.
AB  - This work introduces stopped-flow electrospray ionization (ESI) mass spectrometry
      (MS) as a method for studying fast biochemical reaction kinetics. After
      initiating a reaction by rapid mixing of two solutions, the mixture is
      transferred to a reaction vessel and a steady liquid flow to the ESI source of
      the mass spectrometer is established. The kinetics are studied in real time by
      monitoring selected ion intensities as a function of time. In order to
      characterize the performance of this setup the acid-induced demetallation of
      chlorophyll a was studied. It was found that the reaction is second order in acid
      concentration and that pseudo-first-order rate constants of up to roughly 7 s(-1)
      can be measured reliably. Stopped-flow ESI MS was also applied to study the acid
      induced denaturation of myoglobin. The data presented here confirm the occurrence
      of a short-lived unfolding intermediate during this reaction. Stopped-flow ESI MS
      can provide information that is not accessible by optical rapid-mixing
      experiments. Therefore it appears that this novel technique has the potential to
      become a standard tool for kinetic studies in a number of different fields.

PMID- 11319826
TI  - A ninhydrin-based assay to quantitate the total protein content of tissue
      samples.
AB  - Quantitation of small tissue samples for total protein content is essential for
      many biochemical analyses. In this study a ninhydrin method for measuring the
      total protein content of tissue hydrolysates is presented. The ninhydrin reagent
      is stable at room temperature for up to 1 month in the ethylene glycol-sodium
      acetate solvent system without the requirement for a nitrogen atmosphere. The
      reaction was very accurate and precise, with intra- and interassay variations of
      less than 3% when 5 microg of protein was assayed. All proteins that were
      investigated contributed the same color intensity per microgram protein as bovine
      serum albumin. This assay was several times more sensitive than the Coomassie
      reaction and linear over a greater range of protein concentration.

PMID- 11319825
TI  - Determination of cytochrome P450 metabolites of arachidonic acid in coronary
      venous plasma during ischemia and reperfusion in dogs.
AB  - Arachidonic acid (AA) can be metabolized by cytochrome P450 enzymes to many
      biologically active compounds including 5,6-, 8,9-, 11,12-, and 14,15
      epoxyeicosatrienoic acids (EETs), their corresponding dihydroxyeicosatrienoic
      acids (DHETs), as well as 19- and 20-hydroxyeicosatetraenoic acids (HETEs). These
      eicosanoids are potent regulators of vascular tone. However, their role in the
      ischemic myocardium has not been well investigated. In this study, we used a gas
      chromatographic-mass spectrometric technique to analyze total EETs, DHETs, and 20
      HETE released into coronary venous plasma during coronary artery occlusion and
      reperfusion in anesthetized dogs. Pentafluorobenzyl esters (PFB-esters) of EETs
      and PFB-esters/trimethylsilyl ethers (TMS-ethers) of DHETs and 20-HETE were
      detected in the negative ion chemical ionization (NICI) using methane as a
      reagent gas. Under the conditions used, all four regioisomers of EET eluted from
      the capillary gas chromatographic column at similar retention times while four
      regioisomers of DHETs and 20-HETE eluted separately. The detection limits in
      plasma samples are 5 pg for total EETs, 40 pg for DHET, and 15 pg for 20-HETE.
      14,15-DHET is the major regioisomer detected in the plasma samples while other
      regioisomers of DHETs are probably present at too low a concentration for
      detection. During the first 5 to 15 min of coronary occlusion, a slight decrease
      in the concentration of EETs, 14,15-DHET, and 20-HETE from the control values was
      observed in coronary venous plasma. At 60 min of occlusion, their concentrations
      significantly increased and remained elevated during 5 to 60 min of reperfusion.
      The concentrations decreased at 120 min of reperfusion. The NICI GC-MS was
      successfully used as a sensitive technique to determine cP450 metabolites of AA
      in plasma during prolonged occlusion-reperfusion periods. Furthermore, the
      results indicate that these metabolites may play a role in mediating ischemic
      reperfusion injury.

PMID- 11319827
TI  - Determination of substrate preference in phosphatidylserine decarboxylation by
      liquid chromatography-electrospray ionization mass spectrometry.
AB  - A method has been developed to determine the substrate preference in
      phosphatidylserine decarboxylation (PSD), the process by which phosphatidylserine
      is converted to phosphatidylethanolamine (PE) in the mitochondria. The in vitro
      assay utilized liposomes containing deuterium-labeled PS molecular species
      incubated with liver and brain cortex mitochondria, and the conversion of PS to
      the corresponding PE species was monitored by electrospray ionization mass
      spectrometry in conjunction with reversed-phase liquid chromatography. Employing
      this approach we were able to establish for the first time that there exists a
      substrate preference in PSD in liver (18:0,18:1 > or = 18:0,22:6 > 18:0,20:4-PS)
      and brain cortex (18:0,22:6 > 18:0,18:1 > 18:0,20:4-PS). The observed PSD
      molecular species preference, however, did not reflect the mitochondrial PE
      profile, suggesting that selectivity in other processes such as de novo PE
      synthesis, intracellular transport of phospholipid molecules, or remodeling by
      deacylation-reacylation may be important contributors in maintaining a specific
      lipid profile in mitochondria.

PMID- 11319829
TI  - Gas chromatography/mass spectrometry method to quantify blood hydroxycitrate
      concentration.
AB  - Hydroxycitrate (HCA), a popular dietary supplement for weight loss, is a
      competitive inhibitor of ATP-citrate lyase, an extramitochondrial enzyme involved
      in the initial steps of de novo lipogenesis (DNL). Although animal studies have
      shown that HCA effectively inhibits DNL and induces weight loss, these findings
      have not been consistent in humans. This raises the possibility that the
      bioavailability of HCA may differ among species. We developed a new GC/MS method
      to measure HCA levels in blood, using [U-(13)C]citrate (CA*) as internal standard
      to account for losses associated with the isolation, derivatization, and
      measurement of HCA. HCA and CA* were derivatized with BSTFA + 10% TMCS and
      analyzed using PCI/GC/MS (CA*, m/z 471; and HCA, m/z 553). The plasma HCA
      concentration was measured over a 3.5-h period in four subjects having ingested 2
      g of HCA. Their plasma HCA concentration ranged from 0.8 to 8.4 microg/ml 30 min
      and 2 h after ingestion, respectively. These results demonstrate that when taken
      acutely, HCA is absorbed, yet present in small quantities in human plasma. This
      simple method requiring minimal sample preparation is able to measure trace
      amounts of HCA with accuracy and precision.

PMID- 11319828
TI  - An integrated system to study multiply substituted human immunodeficiency virus
      type 1 reverse transcriptase.
AB  - We describe a gene system allowing the facile production of multiply substituted
      reverse transcriptases (RTs), the enzymatic characterization of these purified
      RTs, and the study of these mutations in the defined genetic background of the
      macrophagetropic, non-laboratory-adapted human immunodeficiency virus type 1 (HIV
      1) AD8 strain. Thirteen unique silent restriction sites were introduced in the
      pol gene encoding HIV-1 RT, allowing easy introduction of mutations. To simplify
      genetic manipulation and generate p66/p51 heterodimers in Escherichia coli, a
      gene construct of the viral protease alone was optimized for expression from a
      separate vector carrying a p15A origin of replication. Active-site titration
      experiments using pre-steady-state kinetics showed that our system yields a
      higher proportion of active enzyme than that obtained by alternate methods. To
      facilitate phenotype/genotype correlations, the modified RT gene was designed to
      be easily reintroduced into a recombinant proviral AD8 HIV-1 DNA. Infectious
      viruses made from this vector were undistinguishable from wild-type AD8 HIV-1, an
      isolate able to infect peripheral blood mononuclear cells and macrophages. Thus,
      the pol gene can tolerate many silent mutations in the polymerase domain without
      affecting the functionality of the HIV-1 genome. The system was validated
      biochemically and virologically using the V75T substitution associated with
      stavudine resistance.

PMID- 11319831
TI  - Horizontal gel electrophoresis of SDS-proteins on the PhastSystem with an at
      least 25-fold increased protein load volume.

PMID- 11319830
TI  - Integration of multiple PCR amplifications and DNA mutation analyses by using
      oligonucleotide microchip.
AB  - We have developed a method for parallel independent on-chip amplification and the
      following sequence variation analysis of multiple DNA regions directly using
      microchip with an array of nanoliter gel pads containing specific sets of
      tethered primers. The method has three key features. First, DNA to be amplified
      is enriched at gel pads by its hybridization with immobilized primers. Second,
      different sets of specific primers are immobilized within various gel pads, and
      primers are detached within gel pads just before polymerase chain reaction to
      enhance the amplification. A gel pad may contain an additional permanently
      immobilized dormant primer that is activated to carry out the allele-specific
      primer extension reaction to detect mutations. Third, multiple polymerase chain
      reactions are confined within nanoliter gel pads covered and separated from each
      other with mineral oil. The method was applied to simultaneously identify several
      abundant drug-resistant mutations in three genes of Mycobacterium tuberculosis.

PMID- 11319832
TI  - Colorimetric quantification of cellobiose employing cellobiose phosphorylase.

PMID- 11319833
TI  - Comparison of three different proliferation assays for mouse myoblast cultures.

PMID- 11319834
TI  - Isolation of recombinant plasmids for rapid analysis using a sodium dodecyl
      sulfate/potassium chloride precipitation.

PMID- 11319835
TI  - Localization of the GLUT1 glucose transporter to brefeldin A-sensitive vesicles
      of differentiated CIT3 mouse mammary epithelial cells.
AB  - Glucose is a precursor of lactose, the major carbohydrate and osmotic constituent
      of human milk, which is synthesized in the Golgi. The GLUT1 glucose transporter
      is the only glucose transporter isoform expressed in the mammary gland. The
      hypothesis that lactogenic hormones induce GLUT1 and cause its localization to
      the Golgi of mammary epithelial cells was tested in CIT(3)mouse mammary
      epithelial cells. Treatment with prolactin and hydrocortisone caused a 15-fold
      induction of GLUT1 by Western blotting, but 2-deoxyglucose uptake decreased.
      Subcellular fractionation and density gradient centrifugation demonstrated
      enrichment of Golgi fractions with GLUT1. Lactogenic hormones enhanced GLUT1
      glycosylation, but did not determine whether GLUT1 was targeted to plasma
      membrane or to Golgi. Confocal microscopy revealed that lactogenic hormones alter
      GLUT1 targeting from a plasma membrane pattern to a predominant perinuclear
      distribution with punctate scattering through the cytoplasm. GLUT1 is targeted to
      a compartment which is more sensitive to Brefeldin A than the compartments in
      which GM130 and beta-COP reside. Targeting of GLUT1 to endosomes was specifically
      excluded. We conclude that prolactin and hydrocortisone induce GLUT1, enhance
      GLUT1 glycosylation, and cause glycosylation-independent targeting of GLUT1 to
      Brefeldin A-sensitive vesicles which may represent a subcompartment of cis-Golgi.
      These results demonstrate a hormonally-regulated targeting mechanism for GLUT1
      and are consistent with an important role for GLUT1 in the provision of substrate
      for lactose synthesis.

PMID- 11319836
TI  - Measurement of fibroblast and bacterial detachment from biomaterials using jet
      impingement.
AB  - Fibroblast and Staphylococcus aureus detachment strength from orthopaedic alloys
      and a tissue culture plastic (Thermanox) have been investigated with jet
      impingement. For S. aureus, unlike fibroblasts, detachment is caused more by
      pressure than shear. For these biomaterials, detachment strength is much higher
      for S. aureus than fibroblasts. Comparing materials under equivalent flow
      conditions, S. aureus attach to stainless steel and titanium with equal strength
      and more strongly than to Thermanox. For fibroblasts, detachment strength from
      all materials was similar. Fibroblast detachment strength from these biomaterials
      substantially decreases with time at equal flow rates and increases with flow
      rate at equal exposure times. Detachment strength is very similar for 3T3 and
      L929 fibroblasts on Thermanox for equivalent flow rate/time combinations, though
      enhanced adhesion of 3T3 cells was often noted for metals. Time effects are less
      evident for S. aureus. S. aureus adhesion to metals is more affected by flow rate
      than fibroblast adhesion.

PMID- 11319837
TI  - Translocation of the IL-1 receptor to focal adhesions is regulated through the C
      terminal end of the cytoplasmic domain.
AB  - The mechanisms of translocation of the IL-1 receptor to focal adhesions were
      analysed using EGFP reporter constructs and confocal microscopy. In fibronectin
      attached cells, the receptor fusion protein was present in distinct punctate
      areas, co-localizing with the transmembrane-linkage protein vinculin. In
      migrating cells, the two proteins co-localized at the leading edge in ruffle-like
      structures. Experiments using a series of receptor mutants revealed that
      translocation of the IL-1 receptor to focal adhesions was dependent on motifs
      conserved between members of the TIR family, in the C-terminal end of the
      receptor. Further, an enhanced level of expression of the wild-type receptor at
      attachment sites was shown to correlate with an increased severity of IL-1
      induced structural effects. This report demonstrates that translocation of the IL
      1 receptor to focal adhesions is dependent on conserved domains in the C-terminal
      end of the protein, and that receptor localization at these sites is important in
      structural regulation of IL-1 mediated responses.

PMID- 11319838
TI  - Tumour necrosis factor-alpha provokes upregulation of alpha2beta1 and alpha5beta1
      integrins, and cell migration in OST osteosarcoma cells.
AB  - OST cells enhance the induction of matrix metalloproteinase (MMP)-9 by tumour
      necrosis factor (TNF)-alpha and the corresponding metastasis to lungs in vivo
      (Kawashima et al., 1994). We focused on the adhesive and migratory properties of
      OST cells, and investigated the expression of integrins in OST cells stimulated
      by TNFalpha in vitro. OST cells potentiated not only adhesion to the
      extracellular matrix (ECM) but also the migration on ECM. On competitive reverse
      transcription-polymerase chain reaction (RT-PCR) analyses, the amounts of alpha2
      (4.9-fold), alpha5 (1.2-fold) and alpha(v) (4.9-fold) were upregulated by
      TNFalpha at the transcriptional level. Alpha-5 showed a slight increase by flow
      cytometry; however, alpha2 and alphav integrins remained unchanged at the protein
      level. Immunofluorescence study disclosed integrins of alpha2beta1 and
      alpha5beta1 were much clustered at cell processes by TNFalpha stimulation,
      probably related to increased cell adhesion and migration. Therefore, the
      upregulation of alpha2beta1 and alpha5beta1 integrins seems to contribute to
      tumour invasion and metastatic potential.

PMID- 11319839
TI  - Cytochrome-C localizes in secretory granules in pancreas and anterior pituitary.
AB  - We used quantitative immunogold electron microscopy to evaluate the subcellular
      distribution of cytochrome-c in normal rat tissues, employing a wide variety of
      monoclonal and polyclonal antibodies against mammalian cytochrome-c. Immunogold
      labeling of tissues embedded in the acrylic resin LR Gold shows highly specific
      labeling of mitochondria in all tissues examined, including adrenal gland,
      cerebellum, cerebral cortex, heart, kidney, liver, pituitary, pancreas, skeletal
      muscle, spleen and thyroid. In pancreatic acinar cells and anterior pituitary,
      however, there was also strong cytochrome-c reactivity in zymogen granules and
      growth hormone granules, respectively. In the pancreas, strong immunoreactivity
      is also detected in condensing vacuoles and in the acinar lumen.
      Immunocytochemical controls included (i) use of monoclonal antibodies to horse
      cytochrome-c which recognize an epitope not present in rat cytochrome-c, (ii)
      preadsorption of antibodies with purified cytochrome-c, and (iii) omission of the
      primary antibody. The indicated presence of cytochrome-c outside mitochondria in
      certain tissues under normal physiological conditions raises interesting
      questions concerning translocation mechanisms and the cellular functions of
      cytochrome-c.

PMID- 11319840
TI  - Ultrastructural evidence that apoptosis is the mechanism by which human amylin
      evokes death in RINm5F pancreatic islet beta-cells.
AB  - A view is emerging that human amylin (HA) kills pancreatic islet beta-cells by
      apoptosis. This study strengthens this view by documenting time-dependent
      morphological and ultrastructural changes in 10 microm HA-treated cultured RINm5F
      islet beta-cells. Membrane blebbing and microvilli loss were the earliest
      detectable apoptosis-related phenomena, already evident 1 h after HA exposure.
      Following 6-12 h of HA-treatment, chromatin margination became evident,
      consistent with detecting DNA laddering about the same time. Nuclear shrinkage,
      nuclear membrane convolution and prominent cytoplasmic vacuolization were clearly
      recognized at 22 h post-treatment. Together, these cellular changes constitute a
      strong case for HA-induced apoptosis, and further demonstrates that electron
      microscopy is a more sensitive tool for early apoptosis detection in cultured
      cells than classical biochemical assays like visualizing DNA laddering. The
      ultrastructural changes reported here contribute further evidence to be included
      in the ongoing dissection of molecular mechanisms underlying HA-induced
      apoptosis, as may occur in type-2 diabetes mellitus.

PMID- 11319841
TI  - Cloning and expression of Munc 30: a member of the paired -like homeodomain gene
      family.
AB  - The temporal and spatial expression of transcription factors is of critical
      importance in the organization and specification of cellular phenotypes in the
      anterior structures of the head and in particular the CNS. In order to identify
      further genes which might play a role in such patterning we have cloned the Munc
      30 gene, a new isoform of the paired -like homeodomain gene Ptx2. Using RT-PCR,
      Munc 30 expression was detected in embryonic head and brain and in a wide panel
      of adult mouse tissues including brain, spinal cord, eye and tongue. In situ
      hybridization showed the expression domain of Munc 30 to be localized to a wide
      variety of developing organs and primordial tissues of the embryo with extremely
      high levels of expression in Rathke's pouch, tooth primordia and the
      hypothalamus. In situ RT-PCR was used to localize gene expression to cells of the
      cortex, striatum and thalamus of adult mouse forebrain. Together, these
      expression patterns suggest that this gene may not only play a critical role in
      patterning of anterior structures of the head during development but may also be
      responsible for the maintenance and/or modulation of cell identity in adult.

PMID- 11319842
TI  - Abnormalities of meiotic division caused by T-DNA tagged mutation in tobacco
      (Nicotiana tabacum L.).

PMID- 11319843
TI  - PDGF-BB and IGF-I use different signaling pathways to induce fibronectin
      synthesis in cultured rat thoracic aortic smooth muscle cells.
AB  - Fibronectin, an extracellular matrix protein, acts as an early signal in
      initiating cell proliferation. Results have indicated that platelet-derived
      growth factor BB (PDGF-BB) and insulin-like growth factor-I (IGF-I) both enhance
      fibronectin gene expression. Genistein inhibits PDGF-BB-induced fibronectin
      levels without inhibiting IGF-I-induced fibronectin levels. It indicates that
      PDGF-BB and IGF-I utilize separate signaling pathways to induce the synthesis of
      fibronectin.

PMID- 11319846
TI  - Locoregionally recurrent breast cancer: incidence, risk factors and survival.
AB  - Locoregional recurrence (LRR) after therapy for early breast cancer is common.
      Patients with LRR can suffer both local consequences and symptoms of metastatic
      disease, as LRR is an independent predictor of subsequent distant metastases.
      Much of the available data on LRR is derived from small, single institution,
      retrospective studies, so marked differences in the incidence rates for LRR, it's
      risk factors and subsequent systemic recurrence are reported. The purpose of this
      review was to try and collate this data in a format that would be useful for both
      clinicians and their patients.

PMID- 11319847
TI  - Does treatment at the time of locoregional failure of breast cancer alter
      prognosis?
AB  - Locoregional recurrence (LRR) after therapy for early breast cancer is common.
      Patients with LRR can suffer local consequences such as bleeding, ulceration,
      pain and arm oedema or symptoms of metastases. Unlike existing treatment
      guidelines for primary tumours, both local (surgical and radiation) and systemic
      treatment recommendations are less well defined after LRR. The purpose of this
      review was to assess whether or not treatment at the time of locoregional failure
      ultimately alters a patient's prognosis. Unfortunately, the data from both
      retrospective and prospective studies are inconclusive and therefore the
      treatment of patients with LRR will continue to be recommended using guidelines
      similar to those for primary breast cancer. Future studies of factors predicting
      LRR and metastatic spread may allow better prognostication of patients with LRR
      which may in turn effect both local and systemic treatment decisions.

PMID- 11319848
TI  - Ovarian cancer chemotherapy.
AB  - The treatment of ovarian cancer has evolved over the past two decades from one of
      palliation to one where patients can achieve prolonged remission and cure.
      Although prognosis remains poor, it has improved with the intervention of a
      multidisciplinary team and greater site specialization in the organization of
      cancer services. The introduction of new chemotherapy agents both as first line
      treatment and on relapse has had a benefit in terms of overall survival and
      progression-free survival. In this review we describe first-line therapy,
      including the use of intraperitoneal chemotherapy, the importance of dose and
      dose intensity in platinum agents and the treatment of refractory and relapsed
      disease. Finally the review focuses on important prognostic factors and how these
      can be used to predict outcome.

PMID- 11319849
TI  - The surgical management of ovarian cancer.
AB  - This article aims to cover current concepts and controversies in the surgical
      management of ovarian cancer. While there have been significant advances in the
      surgical management of vulval, cervical and even endometrial cancer there have
      been few developments in the surgical management of ovarian cancer. This
      situation is likely to continue until we get a clearer understanding of the
      natural history of this disease and better therapeutic options become available.

PMID- 11319850
TI  - Preoperative chemotherapy for non-small cell lung cancer.
AB  - Surgery has been considered the standard of care in patients with early-stage non
      small cell lung cancer (NSCLC), as well as in some cases of stage III, for a long
      time. Poor survival after complete resection has led to the search for new
      therapeutic strategies such as combining anticancer treatments. However, at the
      present time, attempts to combine chemotherapy and radiotherapy after surgery
      have failed to show any significant impact on survival among patients with
      completely resected NSCLC.

PMID- 11319853
TI  - Ecological developmental biology: developmental biology meets the real world.
AB  - The production of phenotype is regulated by differential gene expression.
      However, the regulators of gene expression need not all reside within the embryo.
      Environmental factors, such as temperature, photoperiod, diet, population
      density, or the presence of predators, can produce specific phenotypes,
      presumably by altering gene-expression patterns. The field of ecological
      developmental biology seeks to look at development in the real world of
      predators, competitors, and changing seasons. Ecological concerns had played a
      major role in the formation of experimental embryology, and they are returning as
      the need for knowledge about the effects of environmental change on embryos and
      larvae becomes crucial. This essay reviews some of the areas of ecological
      developmental biology, concentrating on new studies of amphibia and Homo.

PMID- 11319854
TI  - Sparking new frontiers: using in vivo electroporation for genetic manipulations.
AB  - In vivo electroporation is a fascinating new approach by which gene expression,
      regulation, and function can be studied in developmental systems. This technique
      offers new opportunities for manipulations in animal models that lack genetic
      approaches, including avians. Furthermore, this approach is applicable to other
      embryo populations including mice, ascidians, zebrafish, Xenopus, and Drosophila.
      In this review, we discuss technical aspects of in vivo electroporation, review
      recent studies where this approach has been utilized successfully, and identify
      future directions.

PMID- 11319855
TI  - Wnt and BMP signaling govern lineage segregation of melanocytes in the avian
      embryo.
AB  - Recent studies show that specification of some neural crest lineages occurs prior
      to or at the time of migration from the neural tube. We investigated what
      signaling events establish the melanocyte lineage, which has been shown to
      migrate from the trunk neural tube after the neuronal and glial lineages. Using
      in situ hybridization, we find that, although Wnts are expressed in the dorsal
      neural tube throughout the time when neural crest cells are migrating, the Wnt
      inhibitor cfrzb-1 is expressed in the neuronal and glial precursors and not in
      melanoblasts. This expression pattern suggests that Wnt signaling may be involved
      in specifying the melanocyte lineage. We further report that Wnt-3a-conditioned
      medium dramatically increases the number of pigment cells in quail neural crest
      cultures while decreasing the number of neurons and glial cells, without
      affecting proliferation. Conversely, BMP-4 is expressed in the dorsal neural tube
      throughout the time when neural crest cells are migrating, but is decreased
      coincident with the timing of melanoblast migration. This expression pattern
      suggests that BMP signaling may be involved in neural and glial cell
      differentiation or repression of melanogenesis. Purified BMP-4 reduces the number
      of pigment cells in culture while increasing the number of neurons and glial
      cells, also without affecting proliferation. Our data suggest that Wnt signaling
      specifies melanocytes at the expense of the neuronal and glial lineages, and
      further, that Wnt and BMP signaling have antagonistic functions in the
      specification of the trunk neural crest.

PMID- 11319856
TI  - Integrin receptors are required for cell survival and proliferation during
      development of the peripheral glial lineage.
AB  - Proliferation and survival of Schwann cells are important for nerve development
      and for disease processes in peripheral nerves. We have analyzed embryos lacking
      alpha4- or alpha5-integrins and show here that these integrins contribute to the
      control of glial cell numbers. To overcome early embryonic lethality an explant
      and grafting system that allows the study of isolated glial progenitor cells both
      in vitro and in vivo was used. Schwann cells differentiate in the absence of
      alpha5 but their numbers and the proliferation rate of early progenitor cells are
      reduced, suggesting that alpha5 is essential for normal proliferation. Survival,
      rather than proliferation, is compromised in alpha4-deficient explants.
      Conditional immortalization allowed further characterization and revealed that
      alpha4 contributes to survival in a cell-density-dependent fashion. In addition,
      transplants into chicken embryos were used to analyze in vivo cell migration and
      showed that cell death occurs mainly in highly motile, individually migrating
      cells. The cell death patterns in vitro and in vivo argue that alpha4-integrins
      play a role in survival during cell migration. Neural crest migration has been
      suggested to require these integrins; however, no defects in migration were
      observed in the absence of alpha4 or alpha5. We conclude that integrins can
      complement growth factors in the control of glial cell numbers.

PMID- 11319857
TI  - Misexpression of Fgf-4 in the chick limb inhibits myogenesis by down-regulating
      Frek expression.
AB  - Skeletal muscle development involves an initial period of myoblast replication
      followed by a phase in which some myoblasts continue to proliferate while others
      undergo terminal differentiation. The latter process involves the permanent
      cessation of DNA synthesis, activation of muscle-specific gene expression, and
      fusion of single cells to generate multinucleated muscle fibres. The in vivo
      signals regulating the progression through all these steps remain unknown.
      Fibroblast growth factors (Fgfs) and Fgf receptors comprise a large family whose
      members have been shown to play multiple roles in the development of skeletal
      muscle in vitro. Exogenously applied Fgfs are able to stimulate proliferation and
      suppress myogenic differentiation in cell culture. We sought to determine the
      role played by Fgf-4 during limb myogenesis in vivo. Fgf-4 transcripts are
      located at both extremities of myotubes whereas the mRNAs of one of the Fgf
      receptors, Frek, are detected in mononucleated proliferating myoblasts
      surrounding the multinucleated fibres. Overexpression of mouse Fgf-4 (mFgf-4)
      using a replication-competent retrovirus, RCAS, leads to a down-regulation of
      muscle markers followed by an inhibition of terminal differentiation in limb
      muscles. Using quail/chick transplantations we were able to follow the muscle
      cells and found a dramatic decrease in their number after exposure to mFgf-4.
      Interestingly ectopic mFgf-4 down-regulates Frek transcripts in limb muscle
      areas. We conclude that overexpression of mFgf-4 inhibits myoblast proliferation,
      probably by down-regulating Frek mRNAs. This suggests a role for Fgf-4, located
      at the extremities of the myotubes, where it could be responsible for the absence
      of Frek mRNA in the muscle fibre.

PMID- 11319858
TI  - FGF-10 stimulates limb regeneration ability in Xenopus laevis.
AB  - By reciprocal transplantation experiments with regenerative and nonregenerative
      Xenopus limbs, we recently demonstrated that the regenerative capacity of a
      Xenopus limb depends on mesenchymal tissue and we suggested that fgf-10 is likely
      to be involved in this capacity (Yokoyama et al., 2000, Dev. Biol. 219, 18-29).
      However, the data obtained in that study are not conclusive evidence that FGF-10
      is responsible for the regenerative capacity. We therefore investigated the role
      of FGF-10 in regenerative capacity by directly introducing FGF-10 protein into
      nonregenerative Xenopus limb stumps. Exogenously applied FGF-10 successfully
      stimulated the regenerative capacity, resulting in the reinduction of all gene
      expressions (including shh, msx-1, and fgf-10) that we examined and the
      regeneration of well-patterned limb structures. We report here for the first time
      that a certain molecule activates the regenerative capacity of Xenopus limb, and
      this finding suggests that FGF-10 could be a key molecule in possible
      regeneration of nonregenerative limbs in higher vertebrates.

PMID- 11319859
TI  - Calcium-dependent adhesion is necessary for the maintenance of prosomeres.
AB  - Cell adhesion has been suggested to function in the establishment and maintenance
      of the segmental organization of the central nervous system. Here we tested the
      role of different classes of adhesion molecules in prosencephalic segmentation.
      Specifically, we examined the ability of progenitors from different prosomeres to
      reintegrate and differentiate within various brain regions after selective
      maintenance or removal of different classes of calcium-dependent versus 
      independent surface molecules. This analysis implicates calcium-dependent
      adhesion molecules as central to the maintenance of prosomeres. Only conditions
      that spared calcium-dependent adhesion systems but ablated more general (calcium
      independent) adhesion systems resulted in prosomere-specific integration after
      transplantation. Among the members of this class of adhesion molecules, R
      cadherin shows a striking pattern of prosomeric expression during development. To
      test whether expression of this molecule was sufficient to direct progenitor
      integration to prosomeres expressing R-cadherin, we used a retroviral-mediated
      gain-of-function approach. We found that progenitors originally isolated from
      prosomere P2 (a region which does not express R-cadherin), when forced to express
      this molecule, can now integrate more readily into R-cadherin-expressing regions,
      such as the cortex, the ventral thalamus, and the hypothalamus. Nonetheless, our
      analysis suggests that while calcium-dependent molecules are able to direct
      prosomere-specific integration, they are not sufficient to induce progenitors to
      change their regional identity. While diencephalic progenitors from R-cadherin
      expressing regions of prosomere 5 could integrate into R-cadherin-expressing
      regions of the cortex, they did not express the cortex-specific gene Emx1 or the
      telencephalic-specific gene Bf-1. Furthermore, diencephalic progenitors that
      integrate heterotopically into the cortex do not persist postnatally, whereas the
      same progenitors survive and differentiate when they integrate homotopically into
      the diencephalon. Together our results implicate calcium-dependent adhesion
      molecules as key mediators of prosomeric organization but suggest that they are
      not sufficient to bestow regional identities.

PMID- 11319860
TI  - fucosyltransferase1 and H-type complex carbohydrates modulate epithelial cell
      proliferation during prostatic branching morphogenesis.
AB  - The prostate undergoes branching morphogenesis dependent on paracrine
      interactions between the prostatic epithelium and the urogenital mesenchyme. To
      identify cell-surface molecules that function in this process, monoclonal
      antibodies raised against epithelial cell-surface antigens were screened for
      antigen expression in the developing prostate and for their ability to alter
      development of prostates grown in serum-free organ culture. One antibody defined
      a unique expression pattern in the developing prostate and inhibited growth and
      ductal branching of cultured prostates by inhibiting epithelial cell
      proliferation. Expression cloning showed that this antibody binds
      fucosyltransferase1, an alpha-(1,2)-fucosyltransferase that synthesizes H-type
      structures on the complex carbohydrate modifications of some proteins and lipids.
      The lectin UEA I that binds H-type 2 carbohydrates also inhibited development of
      cultured prostates. These data demonstrate a previously unrecognized role for
      fucosyltransferase1 and H-type carbohydrates in controlling the spatial
      distribution of epithelial cell proliferation during prostatic branching
      morphogenesis. We also show that fucosyltransferase1 is expressed by epithelial
      cells derived from benign prostatic hyperplasia or prostate cancer; thus,
      fucosyltransferase1 may also contribute to pathological prostatic growth. These
      data further suggest that rare individuals who lack fucosyltransferase1 (Bombay
      phenotype) should be investigated for altered reproductive function and/or
      altered susceptibility to benign prostatic hyperplasia and prostate cancer.

PMID- 11319861
TI  - Dorsal and ventral positional cues required for the onset of planarian
      regeneration may reside in differentiated cells.
AB  - We previously showed by grafting experiments that the dorsoventral (DV)
      interaction evokes morphogenetic events similar to those that occur in
      regeneration. However, it is not yet understood whether the stem cells themselves
      or differentiated cells have the ability to induce regeneration. Here we
      demonstrated by a combination of X-ray irradiation and grafting experiments that
      the dorsal and ventral positional cues inducing morphogenetic events are retained
      in X-ray-irradiated tissues, suggesting that the differentiated cells may be
      responsible for the positional cues. We grafted a small piece of irradiated worm,
      in which the stem cells were certainly eliminated, to an intact one in DV
      reversed orientation. We observed that projections were developed from the host
      donor boundary, as in the previous experiments. Whole-mount in situ hybridization
      with several markers demonstrated that the projections had a newly established DV
      axis and also had anterior or posterior characteristics. Furthermore, chimeric
      analysis with a strain-specific marker showed that the projections consisted of
      nonirradiated cells and that IFb-expressing cells, which normally belonged to the
      ventral tissue, could be generated even from the stem cells located on the dorsal
      side. Taken together, the findings suggest that the stem cells may simply
      differentiate depending on the surroundings and that differentiated cells may
      present positional cues that induce morphogenesis.

PMID- 11319862
TI  - An acylatable residue of Hedgehog is differentially required in Drosophila and
      mouse limb development.
AB  - The Drosophila Hedgehog protein and its vertebrate counterpart Sonic hedgehog are
      required for a wide variety of patterning events throughout development. Hedgehog
      proteins are secreted from cells and undergo autocatalytic cleavage and
      cholesterol modification to produce a mature signaling domain. This domain of
      Sonic hedgehog has recently been shown to acquire an N-terminal acyl group in
      cell culture. We have investigated the in vivo role that such acylation might
      play in appendage patterning in mouse and Drosophila; in both species Hedgehog
      proteins define a posterior domain of the limb or wing. A mutant form of Sonic
      hedgehog that cannot undergo acylation retains significant ability to repattern
      the mouse limb. However, the corresponding mutation in Drosophila Hedgehog
      renders it inactive in vivo, although it is normally processed. Furthermore,
      overexpression of the mutant form has dominant negative effects on Hedgehog
      signaling. These data suggest that the importance of the N-terminal cysteine of
      mature Hedgehog in patterning appendages differs between species.

PMID- 11319863
TI  - The hiiragi gene encodes a poly(A) polymerase, which controls the formation of
      the wing margin in Drosophila melanogaster.
AB  - The hiiragi (hrg) gene plays a key role in the development of the wing margin in
      Drosophila melanogaster. A mutation in the hrg gene resulted in a decrease in the
      level of the hrg transcript and was associated with a notched wing phenotype. We
      report here that the hrg gene encodes a poly(A) polymerase (PAP). The bovine cDNA
      for PAP type II reversed the phenotype due to mutation of the hrg gene,
      suggesting that hrg might encode a functional homolog of PAP. A mutation that
      reduced the enzymatic activity of Hrg failed to reverse the phenotype of hrg
      mutants, suggesting that the enzymatic activity of Hrg was required to rescue the
      wing phenotype. The levels of expression of wingless and cut at the presumptive
      wing margins were reduced in the late third-instar larvae of hrg mutants. These
      results suggest that the product of hrg is required for the normal expression of
      a series of genes in this region. Our results provide the first evidence that a
      PAP in Drosophila plays a key role in the early development of the wing margin,
      acting to regulate the specific expression of a series of genes via, perhaps,
      control of the processing of the 3' ends of transcripts.

PMID- 11319864
TI  - Laminin-induced change in conformation of preexisting alpha7beta1 integrin
      signals secondary myofiber formation.
AB  - Two distinct populations of myoblasts, distinguishable by alpha7 integrin
      expression have been hypothesized to give rise to two phases of myofiber
      formation in embryonic limb development. We show here that alpha7 integrin is
      detectable far earlier than previously reported on both "primary" and "secondary"
      lineage myoblasts and myofibers. An antibody (1211) that recognizes an
      intracellular epitope allowed detection of alpha7 integrin previously missed
      using an antibody (H36) that recognizes an extracellular epitope. We found that
      when myoblasts were isolated and cultured from different developmental stages,
      H36 only detected alpha7 integrin that was in direct contact with its ligand,
      laminin. Moreover, alpha7 integrin detection by H36 was reversible and highly
      localized to subcellular points of contact between myoblasts and laminin-coated
      2.8-microm microspheres. Prior to secondary myofiber formation in limb
      embryogenesis, laminin was present but not in close proximity to clusters of
      primary myofibers that expressed alpha7 integrin detected by antibody 1211 using
      deconvolution microscopy. These results suggest that the timing of the
      interaction of preexisting alpha7 integrin with its ligand, laminin, is a major
      determinant of allosteric changes that result in an activated form of alpha7
      integrin capable of transducing signals from the extracellular matrix
      commensurate with secondary myofiber formation.

PMID- 11319865
TI  - In vivo functional analysis of ezrin during mouse blastocyst formation.
AB  - During mouse blastocyst formation, a layer of outer cells differentiates in less
      than 48 h into a functional epithelium (the trophectoderm). Ezrin, an actin
      binding structural component of microvilli in epithelial cells, is also involved
      in signal transduction and ionic pump control. In the mouse embryo, ezrin becomes
      restricted to the apical cortex of all blastomeres at compaction and of outer
      cells at later stages. Here we investigated the function of ezrin in living
      embryos during epithelial differentiation using mutant forms of ezrin tagged with
      green fluorescent protein (GFP). GFP-tagged wild-type ezrin (Ez/GFPc) behaved
      like endogenous ezrin and did not interfere with development. Deletion of the
      last 53 amino acids (Delta53/GFP) changed the localization of ezrin: after
      compaction, Delta53/GFP remained associated with the apical and basolateral
      cortex in all blastomeres, and its expression slightly disturbed the cavitation
      process. Finally, full-length ezrin with GFP inserted at position 234 (Ez/GFPi)
      was localized all around the cortex throughout development, although it was
      concentrated at the apical pole after compaction. In embryos expressing Ez/GFPi,
      the duration of the 16-cell stage was reduced, while the onset of cavitation was
      delayed. Moreover, cavitation was abnormal, and the blastocoele was small and
      retracted almost completely several times as if there were major leakages of
      blastocoelic fluid. Our results suggest that, in addition to its role in
      microvilli organization, ezrin is involved in the formation of a functional
      epithelium through a still unknown mechanism.

PMID- 11319867
TI  - Mouse antral oocytes regulate preantral granulosa cell ability to stimulate
      oocyte growth in vitro.
AB  - In this study we evaluated whether mouse oocytes derived from early antral or
      preovulatory follicles could affect the ability of preantral granulosa cells to
      sustain oocyte growth in vitro. We found that early antral oocytes with a
      diameter > or =75 microm did not grow any further during 3 days of culture on
      preantral granulosa cell monolayers in vitro, while most of the oocytes with a
      smaller diameter increased significantly in size. Similarly, about 65% of growing
      oocytes isolated from preantral follicles grew when cultured on preantral
      granulosa cells. By coculturing with growing oocytes fully grown early antral or
      preovulatory oocytes, a small proportion (about 10%) of growing oocytes increased
      in diameter, and changes in granulosa cell morphology were observed. Such effects
      occurred as a function of the fully grown oocyte number seeded and were not
      associated with a decrease in coupling index values. By avoiding physical contact
      between antral oocytes and granulosa cells, the proportion of growing oocytes
      undergoing a significant increase in diameter was about 36%. These results
      indicate that fully grown mouse oocytes can control preantral granulosa cell
      growth-promoting activity through the production of a soluble factor(s) and the
      maintenance of functional communications with surrounding granulosa cells.

PMID- 11319866
TI  - Gprk2 controls cAMP levels in Drosophila development.
AB  - G protein-coupled receptors mediate their biological responses through the
      generation of second messengers, such as cAMP. The down-regulation of their
      activity (desensitization) is carried out, in part, by the family of G protein
      coupled receptor kinases, which phosphorylate activated receptors. The Gprk2 gene
      in Drosophila melanogaster is a putative member of this family. The GPRK2 protein
      is expressed most abundantly in the ovaries and in the mushroom bodies, the brain
      region that is implicated in learning and memory in insects. Many of the genes
      that are involved in learning in Drosophila are members of a cAMP-signaling
      pathway and are also expressed in the mushroom bodies. These observations suggest
      that the Gprk2 gene may be involved in a cAMP-mediated pathway. To investigate
      this possibility, we tested for a genetic interaction between Gprk2 and dunce
      (which encodes cAMP-specific phosphodiesterase). A mutant allele of Gprk2, called
      gprk2(6936), has decreased fertility as a result of reduced levels of egg laying
      and hatching, and developing egg chambers display defects in the formation of
      anterior structures. Similarly, many alleles of dunce are sterile, with an ovary
      phenotype that resembles gprk2(6936). Introduction of a single copy of a
      hypomorphic or null allele of dunce into the gprk2(6936) background suppressed
      all of these defects to a significant degree. Suppression was also observed when
      a single copy of gprk2(6936) was introduced into a dunce background. Like mutants
      of rutabaga (which encodes a calcium/calmodulin-dependent adenylate cyclase),
      gprk2(6936) has reduced levels of cAMP. Ovaries from gprk2(6936) females contain
      about one third of the normal amount of cAMP. In addition, in every mutant
      combination where fertility is increased, cAMP levels are closer to wild type
      levels. These results suggest that Gprk2 is functioning in a cAMP-signaling
      pathway and that the underlying basis of the interaction between Gprk2 and dunce
      is a normalization of cAMP levels.

PMID- 11319868
TI  - Factors controlling the loss of immunoreactive somatic histone H1 from blastomere
      nuclei in oocyte cytoplasm: a potential marker of nuclear reprogramming.
AB  - Nuclei of differentiated cells can acquire totipotency following transfer into
      the cytoplasm of oocytes. While the molecular basis of this nuclear reprogramming
      remains unknown, the developmental potential of nuclear-transfer embryos is
      influenced by the cell-cycle stage of both donor and recipient. As somatic H1
      becomes immunologically undetectable on bovine embryonic nuclei following
      transfer into ooplasm and reappears during development of the reconstructed
      embryo, suggesting that it may act as a marker of nuclear reprogramming, we
      investigated the link between cell-cycle state and depletion of immunoreactive H1
      following nuclear transplantation. Blastomere nuclei at M-, G1-, or G2-phase were
      introduced into ooplasts at metaphase II, telophase II, or interphase, and the
      reconstructed embryos were processed for immunofluorescent detection of somatic
      histone H1. Immunoreactivity was lost more quickly from donor nuclei at metaphase
      than at G1 or G2. Regardless of the stage of the donor nucleus, immunoreactivity
      was lost most rapidly when the recipient cytoplast was at metaphase and most
      slowly when the recipient was at interphase. When the recipient oocyte was not
      enucleated, however, immunoreactive H1 remained in the donor nucleus. The
      phosphorylation inhibitors 6-DMAP, roscovitine, and H89 inhibited the depletion
      of immunoreactive H1 from G2, but not G1, donor nuclei. In addition,
      immunoreactive H1 was depleted from mouse blastomere nuclei following transfer
      into bovine oocytes. Finally, expression of the developmentally regulated gene,
      eIF-1A, but not of Gapdh, was extinguished in metaphase recipients but not in
      interphase recipients. These results indicate that evolutionarily conserved cell
      cycle-regulated activities, nuclear elements, and phosphorylation-linked events
      participate in the depletion of immunoreactive histone H1 from blastomere nuclei
      transferred in oocyte cytoplasm and that this is linked to changes in gene
      expression in the transferred nucleus.

PMID- 11319870
TI  - Growing dictyate oocytes, but not early preimplantation embryos, of the mouse
      display high levels of DNA homologous recombination by single-strand annealing
      and lack DNA nonhomologous end joining.
AB  - We have investigated the ability of growing dictyate oocytes and early
      preimplantation embryos of the mouse to process extrachromosomal DNA molecules
      with free ends by intranuclearly microinjecting DNA fragments containing a region
      of homology of various extent at either the 5' or 3' terminus. Homologous
      recombination of these fragments by single-strand annealing (SSA), but not other
      DNA recombination/joining mechanisms, resulted in the formation of a full-length
      hsp-lacZ-pA fusion gene that was transcriptionally activated by heat shock in
      growing oocytes and spontaneously at the early two-cell stage in the embryos,
      making it possible to quantitatively evaluate SSA activities of these cells by
      the beta-galactosidase produced. SSA activities of oocytes and embryos were
      similar in their general properties and in the activity levels observed with
      saturating amounts of DNA. However, embryo SSA was almost one order of magnitude
      less effective than that of oocytes. Oocyte and embryo 5' --> 3' exonuclease (a
      key function of the SSA pathway) and DNA nonhomologous end joining (NHEJ)
      activities were also investigated using an asymmetric PCR assay. Results showed
      that NHEJ is lacking in oocytes and is very prominent in the embryos, where it
      competes with SSA for the injected DNA.

PMID- 11319869
TI  - Analysis of loss of adhesive function in sperm lacking cyritestin or fertilin
      beta.
AB  - We produced mice lacking the sperm surface protein cyritestin (ADAM 3) and found
      mutant males are infertile. Similar to fertilin beta (ADAM 2) null sperm (C. Cho
      et al., 1998, Science 281, 1857-1859), cyritestin null sperm are drastically
      deficient in adhesion to the egg zona pellucida (0.3% of wild type) and to the
      egg plasma membrane (9% of wild type). Thus sperm from male mice with a gene
      deletion of either ADAM have a loss of adhesive function in at least two steps of
      fertilization. We found deletion of either ADAM gene resulted in the loss of
      multiple gene products. This loss of multiple gene products (sperm membrane
      proteins) appears to result from a novel, developmental mechanism during sperm
      differentiation. Because the altered sperm protein expression must be responsible
      for the fertilization defects, our data suggest new models for the molecular
      basis of the affected steps in fertilization.

PMID- 11319871
TI  - The phosphorylated C-terminus of cAR1 plays a role in cell-type-specific gene
      expression and STATa tyrosine phosphorylation.
AB  - cAMP receptors mediate some signaling pathways via coupled heterotrimeric G
      proteins, while others are G-protein-independent. This latter class includes the
      activation of the transcription factors GBF and STATa. Within the cellular mounds
      formed by aggregation of Dictyostelium, micromolar levels of cAMP activate GBF
      function, thereby inducing the transcription of postaggregative genes and
      initiating multicellular differentiation. Activation of STATa, a regulator of
      culmination and ecmB expression, results from cAMP receptor-dependent tyrosine
      phosphorylation and nuclear localization, also in mound-stage cells. During mound
      development, the cAMP receptor cAR1 is in a low-affinity state and is
      phosphorylated on multiple serine residues in its C-terminus. This paper
      addresses possible roles of cAMP receptor phosphorylation in the cAMP-mediated
      stimulation of GBF activity, STATa tyrosine phosphorylation, and cell-type
      specific gene expression. To accomplish this, we have expressed cAR1 mutants in a
      strain in which the endogenous cAMP receptors that mediate postaggregative gene
      expression in vivo are deleted. We then examined the ability of these cells to
      undergo morphogenesis and induce postaggregative and cell-type-specific gene
      expression and STATa tyrosine phosphorylation. Analysis of cAR1 mutants in which
      the C-terminal tail is deleted or the ligand-mediated phosphorylation sites are
      mutated suggests that the cAR1 C-terminus is not essential for GBF-mediated
      postaggregative gene expression or STATa tyrosine phosphorylation, but may play a
      role in regulating cell-type-specific gene expression and morphogenesis. A mutant
      receptor, in which the C-terminal tail is constitutively phosphorylated, exhibits
      constitutive activation of STATa tyrosine phosphorylation in pulsed cells in
      suspension and a significantly impaired ability to induce cell-type-specific gene
      expression. The constitutively phosphorylated receptor also exerts a partial
      dominant negative effect on multicellular development when expressed in wild-type
      cells. These findings suggest that the phosphorylated C-terminus of cAR1 may be
      involved in regulating aspects of receptor-mediated processes, is not essential
      for GBF function, and may play a role in mediating subsequent development.

PMID- 11319872
TI  - The education of an academic surgeon.

PMID- 11319873
TI  - 18F-labeled fluorodeoxyglucose positron emission tomography-guided surgery for
      recurrent colorectal cancer: a feasibility study.
AB  - OBJECTIVE: Positron emission tomography (PET) scanning is an accepted diagnostic
      tool for the detection of colorectal cancer (CRC). The purpose of this study was
      to determine whether diagnostic information offered by preoperative PET scan
      could be used to detect disease intraoperatively using beta and gamma handheld
      probes. METHODS: Two studies were carried out. First, tumor "phantoms" were
      created using 62 microCi fluorodeoxyglucose (FDG) in a saline-filled basin. Gamma
      and beta handheld probes were used to determine detection characteristics with
      respect to probe type, distance from source, and isotope half-life. In a second
      study, probes were used intraoperatively to detect tumor in 10 patients with
      recurrent colorectal cancer as determined by preoperative PET scan. Counts
      relative to background were determined for each probe as was histopathologic
      correlation with probe-positive tissue. RESULTS: Phantom studies documented that
      FDG detection by each probe was nonlinearly related to source proximity and half
      life. In human subjects, abnormal findings on preoperative PET studies were
      detected by both probes with tumor:normal ratios of 1.6 (beta) and 1.5 (gamma).
      All probe-positive tissue was histologically confirmed to be recurrent colorectal
      cancer. CONCLUSIONS: Intraoperative detection of CRC using an FDG source and beta
      and gamma probes correlates with preoperative PET. With further improvements in
      probe technology, successful differentiation of normal and tumor tissue as shown
      here may allow for more precise localization and directed resection.

PMID- 11319874
TI  - Tumor cell adhesion to endothelial cells is increased by endotoxin via an
      upregulation of beta-1 integrin expression.
AB  - BACKGROUND: Recent studies have demonstrated that metastatic disease develops
      from tumor cells that adhere to endothelial cells and proliferate
      intravascularly. The beta-1 integrin family and its ligand laminin have been
      shown to be important in tumor-to-endothelial cell adhesion. Lipopolysaccharide
      (LPS) has been implicated in the increased metastatic tumor growth that is seen
      postoperatively. We postulated that LPS increases tumor cell expression of beta-1
      integrins and that this leads to increased adhesion. METHODS: The human
      metastatic colon cancer cell line LS174T was labeled with an enhanced green
      fluorescent protein (eGFP) using retroviral transfection. Cell cultures were
      treated with LPS for 1, 2, and 4 h (n = 6 each) and were subsequently cocultured
      for 30 or 120 min with confluent human umbilical vein endothelial cells (HUVECs),
      to allow adherence. Adherent tumor cells were counted using fluorescence
      microscopy. These experiments were carried out in the presence or absence of a
      functional blocking beta-1 integrin monoclonal antibody (4B4). Expression of beta
      1 integrin and laminin on tumor and HUVECs was assessed using flow cytometric
      analysis. Tumor cell NF-kappaB activation after incubation with LPS was measured.
      RESULTS: Tumor cell and HUVEC beta-1 integrin expression and HUVEC expression of
      laminin were significantly (P < 0.05) enhanced after incubation with LPS. Tumor
      cell adhesion to HUVECs was significantly increased. Addition of the beta-1
      integrin blocking antibody reduced tumor cell adhesion to control levels. LPS
      increased tumor cell NF-kappaB activation. CONCLUSIONS: Exposure to LPS increases
      tumor cell adhesion to the endothelium through a beta-1 integrin-mediated pathway
      that is NF-kappaB dependent. This may provide a target for immunotherapy directed
      at reducing postoperative metastatic tumor growth.

PMID- 11319875
TI  - Flow-induced DNA synthesis requires signaling to a translational control pathway.
AB  - BACKGROUND: The mTOR translational control pathway that signals to the P70/P85 S6
      kinase (pp70(S6k)) is essential for mitogenesis. We have previously shown that
      pp70(S6k) is activated by fluid flow. We hypothesized that oscillatory fluid flow
      in the absence of exogenous mitogens would induce endothelial cells to synthesize
      DNA via activation of the mTOR pathway. For comparison, we also studied the
      ERK1/2 transcriptional signaling pathway. METHODS: Confluent human umbilical vein
      endothelial cells (HUVECs) were exposed to oscillatory flow (12 dyn/cm(2) peak
      shear stress; 3.3 Hz) or kept static in serum-deprived culture medium. Rapamycin
      or PD98059 was used to inhibit pp70(S6k) or ERK1/2 activation, respectively.
      RESULTS: Oscillatory flow activated both the pp70(S6k) and ERK1/2 signaling
      pathways. Rapamycin blocked activation of pp70(S6k) but not ERK1/2, while PD98059
      blocked ERK1/2 but not pp70(S6k). DNA synthesis, as measured by [3H]thymidine
      uptake, increased by approximately twofold (P < 0.01) in HUVEC cultures exposed
      to oscillatory flow compared with those kept static. Rapamycin completely
      abolished the flow-induced increase in DNA synthesis while PD98059 did not.
      Oscillatory flow upregulated expression of cyclin-dependent kinases 1 and 4 mRNA
      in a temporal pattern consistent with cell cycle entry; rapamycin also inhibited
      these changes. CONCLUSIONS: Oscillatory flow activates both the ERK 1/2 and
      pp70(S6k) signaling pathways in HUVECs and induces DNA synthesis in the absence
      of other exogenous mitogens. Complete blockade of [3H]thymidine uptake by the
      mTOR pathway inhibitor rapamycin indicates that separate and distinct signaling
      to a translational control pathway is necessary to mediate flow-induced DNA
      synthesis by endothelial cells. Oscillatory flow-induced endothelial
      proliferation may contribute to atherogenesis.

PMID- 11319876
TI  - Open-heart endocardial radiofrequency ablation: an alternative to incisions in
      Maze surgery.
AB  - BACKGROUND: Radiofrequency (RF) ablation produces transmural atrial lesions in
      vitro, and may provide advantages over incisions currently used in maze surgery.
      This study examines the feasibility, safety, and efficacy of open-heart
      endocardial RF ablation. METHODS: Eighteen sheep (42.8 +/- 4.4 kg, age < 2 years)
      underwent left thoracotomy with placement of pacing leads on a pulmonary vein and
      the left atrial dome. On cardiopulmonary bypass, lesions were made using incision
      and suture or a novel RF ablation device in three sites: PVC = circle excluding
      pulmonary veins, IAB = line across the interatrial bundle, SVC = line from the
      superior to the inferior vena cava. Pacing across the PVC lesion was attempted to
      assess the completeness of each lesion. Preselected animals (incision n = 4, RF n
      = 5) were recovered and pacing attempts were repeated at 1 month. After
      sacrifice, hearts were sectioned and measured for lesion size and completeness.
      RESULTS: RF ablation lesions took less time to create (total bypass time: RF 51.8
      min vs incision 106 min, P < 0.001). No evidence of thromboembolism, atrial
      rupture, or coronary sinus thrombosis was seen. All PVC lesions were complete as
      demonstrated by the inability to pace across them. Stained sections demonstrated
      that acutely studied incision lesions were thinner than RF lesions; however, all
      lesions were transmural and similar in width at 1 month. CONCLUSIONS: RF ablation
      consistently created transmural lesions more quickly than the incision and suture
      method and without additional complications. Endocardial RF ablation appears to
      be a simple and effective alternative to surgical incisions during open-heart
      atrial Maze procedures.

PMID- 11319877
TI  - VEGF is upregulated in a neuroblastoma and hepatocyte coculture model.
AB  - BACKGROUND: We hypothesize that angiogenic factors are altered by the interaction
      between neuroblastoma cells and host tissues. MATERIALS AND METHODS: Human Chang
      hepatocytes and human neuroblastoma cells are cultured separately and in a
      noncontact, coculture system. Immunostaining for VEGF is performed on the cells.
      ELISA is used to detect vascular endothelial growth factor (VEGF), basic
      fibroblast growth factor, and interleukin-8 in the conditioned media. Human
      umbilical vein endothelial cells (HUVEC) are cultured with standard medium
      (control) and hepatocyte, neuroblastoma, and coculture conditioned media. After
      48 and 72 h, cells are counted to determine proliferation. Finally, VEGF-blocking
      antibody is added to the HUVEC cultures with the conditioned media. RESULTS: VEGF
      is markedly elevated in the coculture medium compared to the media from
      hepatocytes or neuroblastoma grown alone [412.2 +/- 52 vs 235 +/- 35 or 74.5 +/-
      28.5 (pg/10(6) cells), P < 0.05]. Other growth factors are almost undetectable in
      any of the media. Immunostaining for VEGF in the cocultured hepatocytes is
      decreased by almost 50%, but VEGF immunostaining is increased fourfold in the
      cocultured neuroblastoma cells. A significant increase in cell proliferation is
      seen at both 48 and 72 h when HUVEC are cultured with the coculture media. Cell
      proliferation is blocked with the addition of anti-VEGF antibody. CONCLUSION: The
      interaction of neuroblastoma with hepatocytes results in an increased production
      of VEGF. It stimulates endothelial cell proliferation and may enhance the tumor's
      metastatic potential in an autocrine fashion.

PMID- 11319878
TI  - Lack of enteral feeding increases expression of E-selectin after LPS challenge.
AB  - BACKGROUND: Total parenteral nutrition (IV-TPN) increases neutrophil accumulation
      in the small intestine, expression of intestinal ICAM-1 and P-selectin, and
      upregulates E-selectin expression in the lung. Endothelial activation induced by
      lack of enteral nutrition may change the response to injury or infection. This
      study investigated whether nutrition influenced the expression of the adhesion
      molecule, E-selectin and ICAM-1, following endotoxin challenge. MATERIALS AND
      METHODS: Forty-three mice were injected with saline, 2, 20, 200, 2000, or 10000
      microg/kg lipopolysaccharide (LPS) intraperitoneally. E-selectin expression in
      the lung, small intestine, and heart was quantified at 3 h after challenge, while
      ICAM-1 was measured at 5 h, using the dual-radiolabeled monoclonal antibody
      technique. Next, 80 mice were fed chow, intragastric (IG)-TPN, or IV-TPN for 5
      days, and then received intraperitoneal 2 or 200 microg/kg LPS. E-selectin and
      ICAM-1 expression in organs was measured at 3 and 5 h after endotoxin,
      respectively. RESULTS: E-selectin expression in organs increased LPS dose
      dependently. ICAM-1 levels reached early peaks in the lung and in the intestine.
      Also, IV-TPN significantly increased E-selectin expression in the small intestine
      and tended to increase pulmonary E-selectin, when compared to chow or IG-TPN
      animals. There were no significant differences in E-selectin expression among
      three diet groups after 200 microg/kg LPS challenge. No differences in ICAM-1
      expression were observed in any organ among the three groups after 2 or 200
      microg/kg LPS injection. CONCLUSIONS: E-selectin rather than ICAM-1, because of
      the expression pattern after various dosages of LPS challenge, may be a
      determining factor for the degree of LPS-induced inflammation at the early phase.
      Lack of enteral nutrition may increase inflammatory response through enhanced gut
      E-selectin levels after a small dose of LPS.

PMID- 11319879
TI  - Bile salt stimulates intestinal epithelial cell migration through TGFbeta after
      wounding.
AB  - BACKGROUND: In addition to aiding in the digestion of fats, luminal bile salts
      have been shown to modulate gastrointestinal epithelial growth, differentiation,
      and other functions. We hypothesized that bile acids could modulate the
      intestinal mucosal repair process of restitution. We investigated the effect of
      the bile salt taurodeoxycholic acid on epithelial migration and identified a role
      for TGFbeta, a widely expressed cytokine in the intestinal villus, in this repair
      process. METHODS: Using a well-established model of epithelial restitution, IEC-6
      cells were plated on 60-mm Matrigel-coated plastic dishes and grown to
      confluence. The epithelium was wounded by scraping with a 6-mm-wide blade to
      create a smooth denuded edge and cell migration was measured 8 h later. Cells
      were grown in control DMEM with 5% FBS with or without 0.01-2 mM taurodeoxycholic
      acid (TDCA). In parallel experiments, cells were harvested for Northern analysis
      of TGFbeta and GAPDH expression; [3H]thymidine uptake was used to measure
      proliferation. Anti-TGFbeta antibody was added to cells grown in the presence of
      0.05 mM TDCA and migration was measured at 8 h. RESULTS: TDCA at physiologic
      luminal concentrations augments IEC-6 cell migration, with a maximal effect at
      0.05 mM. TDCA inhibited proliferation at these concentrations. TGFbeta expression
      increased in response to bile acid, while wounding had less of an effect on
      TGFbeta expression. Blockade of TGFbeta function with TGFbeta antibody eliminated
      the effect of bile on cell migration. CONCLUSIONS: Bile acid at physiologic
      concentrations augments small intestinal epithelial cell migration. The process
      is dependent on TGFbeta and is independent of cell division. The data further
      support a role for bile acids and TGFbeta in differentiated intestinal cell
      function and in preservation of an intact mucosa.

PMID- 11319880
TI  - Endotoxin (LPS) stimulates 4E-BP1/PHAS-I phosphorylation in macrophages.
AB  - INTRODUCTION: Translational control of cytokine production in endotoxin (LPS)
      stimulated macrophages is poorly characterized but likely important. An early
      step in protein translation is engagement of mRNA by eukaryotic initiation factor
      4E (eIF-4E). Translation initiation can be prevented by small 4E-binding proteins
      (4E-BP1 or PHAS-I) which must be phosphorylated in order to disengage eIF-4E. We
      examined whether LPS alters 4E-BP1 phosphorylation in macrophages. MATERIALS AND
      METHODS: Elicited rat peritoneal macrophages and Raw 264.7 macrophages were
      treated with signal transduction inhibitors and then LPS. Cells were harvested
      and equal protein amounts were electrophoresed (SDS-PAGE). Western blots (WB)
      were developed with 4E-BP1 antibody. Alternatively cell lysates were exposed to 7
      methyl GTP Sepharose beads in order to isolate the cap-binding protein eIF-4E.
      The relative amounts of 4E-BP1 associated with eIF-4E were then determined by WB.
      RESULTS: Macrophage 4E-BP1 is phosphorylated upon stimulation by LPS as evidenced
      by the appearance of a more slowly migrating gamma (hyperphosphorylated) band on
      gel electrophoresis. Inhibition of both the p42/p44 MAPK pathway (PD 98059) and
      the p38 MAPK pathway (SB 203580) failed to alter LPS-induced 4E-BP1
      phosphorylation. Rapamycin (FRAP/mTOR inhibitor) blocked 4E-BP1 phosphorylation
      causing a predominance of the alpha (hypophosphorylated) band. This was confirmed
      further by 7-methyl-GTP Sepharose isolation of eIF-4E with which 4E-BP1
      coprecipitates. CONCLUSION: LPS stimulates 4E-BP1 phosphorylation in macrophages
      through FRAP/mTOR signaling. This pathway may contribute to the translational
      control of cytokine gene expression in macrophages.

PMID- 11319881
TI  - Epithelial cyclooxygenase-2 expression: a model for pathogenesis of colon cancer.
AB  - BACKGROUND: Recent studies indicate a close relationship between cyclooxygense-2
      (COX-2) expression and the pathogenesis of colorectal cancer, yet little
      information exists regarding the stimuli and pathways involved in COX-2
      expression by the colonic epithelium. We studied the induction of COX-2 in
      response to such environmental stress as hyperosmolarity and lipopolysaccharide
      (LPS) in a human colon cell line. We further investigated the transduction
      cascades mediating COX-2 expression, focusing upon the mitogen-activated protein
      kinase pathways p38 and extracellular signal-regulated kinase (ERK). MATERIALS
      AND METHODS: Human colon cancer cells (Caco-2) were stimulated with increasing
      concentrations of sodium chloride (NaCl) or LPS. Total protein was extracted at
      different time points and subjected to Western blot analysis with antibodies to
      human COX-2, COX-1, or phospho-specific antibodies to ERK and p38. RESULTS: LPS
      failed to induce COX-2 or COX-1 expression. Hyperosmolarity induced COX-2
      expression by 2 h, with peak levels occurring at 6-8 h. NaCl at 40 and 100 mM
      induced a 2-fold and more than 50-fold increase in COX-2 expression,
      respectively; COX-1 expression was not affected. Hyperosmolarity induced both p38
      and ERK activation within 30 min; however, only p38 inhibition attenuated osmotic
      induced COX-2 expression; inhibition of ERK activation had no effect.
      CONCLUSIONS: Increase in osmolarity activates p38 and induces COX-2 expression in
      the colonic epithelium. The lack of response to LPS is teleologically expected of
      the colonic epithelium that is in constant contact with the fecal bacteria. This
      model also predicts that an increase in luminal osmolarity in the colon may
      induce COX-2 and thereby promote a neoplastic phenotype.

PMID- 11319882
TI  - Epithelial permeability is not increased in rats following small bowel resection.
AB  - BACKGROUND: Increased intestinal permeability and translocation of bacteria
      and/or bacterial products may cause infection and liver dysfunction in patients
      with the short bowel syndrome. In previous studies, serum from mice undergoing
      small bowel resection (SBR) enhanced growth of cultured rat intestinal epithelial
      cells (RIEC-6), implicating a role for a serum factor(s) in the enterocyte
      response to SBR. These experiments tested the hypothesis that epithelial cell
      permeability is increased following SBR. MATERIALS AND METHODS: Male Sprague
      Dawley rats underwent a 75% SBR or sham operation. Intestinal permeability in the
      remnant ileum was determined by Ussing chambers on Postoperative Day (POD) 3.
      Additionally, serum was collected on POD 1, 3, and 7 and mesenteric lymph was
      harvested on POD 3. Once confluent, RIEC-6 cells were incubated for 3 days in
      media supplemented with 10% fetal bovine serum (FBS; control), 1% FBS, 1% FBS
      plus 9% Sham serum, or 1% FBS plus 9% SBR serum or exposed to media with varied
      concentrations of SBR or Sham lymph. Monolayer permeability was determined by
      measuring the passage of dextran-rhodamine. RESULTS: Intestinal permeability was
      reduced in rats undergoing SBR. Sham serum-treated monolayers demonstrated the
      greatest permeability. Incubation with SBR serum reduced permeability to near
      control media. There were no permeability differences between SBR and Sham lymph
      treated monolayers. CONCLUSION: The early adaptive response of the remnant
      intestine after SBR is associated with reduced permeability. These results
      suggest an alternative mechanism for the increased bacterial translocation that
      has been described following SBR.

PMID- 11319883
TI  - Comparison of performance 2 years after the old and new (interactive) ATLS
      courses.
AB  - BACKGROUND: We previously (1997) demonstrated superior clinical but similar
      cognitive performance after the new interactive compared to the old ATLS course.
      The present study is aimed at determining whether this difference was short term
      or maintained over time (2 years). MATERIALS AND METHODS: Two groups of 13
      physicians out of the original 32 physicians were available for the study which
      compared performance in a 40-item MCQ examination on trauma topics and clinical
      performance in 4 trauma OSCE stations consisting of simulated trauma patients.
      Paired and unpaired t tests were used for within- and between-group comparisons,
      respectively, with P < 0.05 being considered statistically significant. Overall
      OSCE scores (maximum standard 20), adherence to priority scores (Priority, scale
      1 to 7), and overall approach (Approach, scale 1 to 5) scores were analyzed.
      RESULTS: Values are means +/- SD; (+)-P < 0.05 compared to 1999; *P < 0.05
      compared to old group [table in text]. CONCLUSIONS: Although knowledge base
      decreases similarly with time after both courses, the new interactive course
      participants maintained a consistently higher clinical skill performance level at
      2 years.

PMID- 11319884
TI  - Extrinsic neural innervation mediates absorption of water and electrolytes in
      canine proximal colon in vivo.
AB  - INTRODUCTION: Extrinsic innervation mediates a proabsorptive effect in small
      intestine. Our aim was to determine whether extrinsic neural input modulates
      similar effects in the proximal colon in vivo. METHODS: Ten adult dogs underwent
      enteric isolation of a 50-cm proximal colon loop; five each were randomized to
      undergo extrinsic denervation (Ext Den) of the isolated colonic segment or to
      serve as neurally innervated controls. After recovery, a 38 degrees C electrolyte
      solution (Na(+) 125 meq/L, K(+) 9 meq/L, Cl(-) 75 meq/L, HC03(-) 65 meq/L) was
      infused at 4 ml/min into the segment. Effluent was collected in 30-min intervals
      for 2 h after achieving steady state (determined by 14C nonabsorbable marker
      recovery); four studies were conducted at 1 and 12 weeks postoperatively. Net
      flux of H20, Na(+), K(+), and Cl(-) was determined. Colon morphometry was
      evaluated at 0 and 14 weeks. Data are presented as mean +/- SEM. Unpaired t test
      was applied for comparisons. RESULTS: Net absorptive flux of H20 (microL/min/cm)
      was decreased in Ext Den vs controls at 1 week (4.40 +/- 0.63 vs 7.92 +/- 0.92, P
      = 0.03) but was not different at 12 weeks (4.70 +/- 1.20 vs 5.97 +/- 0.69; P >
      0.05). Na(+) and Cl(-) followed the trends in H20 absorption (P < or = 0.05).
      Crypt depth (microm) decreased in controls at 14 weeks vs 0 week (915 +/- 20 vs
      740 +/- 07, P = 0.01) but remained unchanged in Ext Den. CONCLUSIONS: Loss of
      extrinsic neural input decreases colonic absorption. This observation suggests
      that extrinsic neural innervation provides net proabsorptive mechanisms for
      absorption of water and electrolytes in the proximal canine colon.

PMID- 11319885
TI  - Preoperative treatment with recombinant human growth hormone prevents ischemia
      reperfusion-induced diaphragmatic dysfunction.
AB  - BACKGROUND: Respiratory complications continue to be a major cause of morbidity
      and mortality following major vascular surgery. The recent UK Small Aneurysm
      Trial cited preoperative respiratory function as the major predictor of outcome
      following elective aortic surgery. AIM: The aim of this study was to investigate
      the effect of aortic clamping and revascularization on diaphragmatic muscle
      function in a small animal model and to evaluate the role of preoperative
      treatment with recombinant human growth hormone (rhGH) in preventing
      diaphragmatic muscle dysfunction. METHODS: Male Sprague-Dawley rats (n = 18) were
      randomized into one of three groups: control (n = 6) underwent laparotomy only;
      IR (n = 6) had a laparotomy with infrarenal cross-clamping for 30 min followed by
      lower torso revascularization for 2 h; IR + rhGH (n = 6) were treated with rhGH
      (Genotropin 0.3 IU/kg/day) for 5 days before laparotomy and aortic cross-clamping
      for 30 min followed by lower torso revascularization for 2 h. Diaphragmatic
      muscle contractile function was assessed ex vivo using electrical field
      stimulation in a tissue bath. RESULTS: Two hours of IR injury resulted in a
      significant impairment in diaphragmatic twitch (Control, 242.01 + 38.45 g; IR,
      108.55 + 7.15 g). This impairment was prevented by pretreatment with rhGH (rhGH,
      319.14 + 30.71 g; P < 0.01). Tetanic function was also significantly impaired by
      ischemia reperfusion injury (control, 605 + 77.63 g; IR, 228.12 + 14.38 g).
      Again, pretreatment with rhGH prevented this deterioration (IR + rhGH, 704.39 +
      45.69 g; P < 0.05) compared with controls. CONCLUSION: The results of this study
      suggest that preoperative administration of rhGH may have a role in preventing
      the diaphragmatic dysfunction associated with infrarenal aortic cross-clamping
      and revascularization.

PMID- 11319886
TI  - Pericytes augment the capillary barrier in in vitro cocultures.
AB  - Most in vitro studies of capillary permeability focus on endothelial cell (MVEC)
      monolayers and ignore the second cell that forms the capillary wall: the
      microvascular pericyte (PC). We describe a model to study the permeability
      characteristics of MVEC, PC, and MVEC:PC cocultures. METHODS: Semipermeable
      culture inserts were coated with collagen and then plated with early passage
      bovine pulmonary MVEC. On Day 3, bovine pulmonary PC were added at concentrations
      to approximate MVEC:PC ratios of 1:1, 5:1, and 10:1. Electrical resistance was
      measured on subsequent days and fluorescently labeled (FITC) albumin was used in
      a permeability assay to calculate an albumin clearance for each culture. RESULTS:
      The results for electrical resistance measurements and albumin assays showed a
      similar pattern. Resistance for endothelial cell monolayers was significantly
      higher and albumin permeability was significantly lower than that of controls.
      Addition of pericytes at a 10:1 and 5:1 ratios increased the permeability barrier
      compared to endothelial cells alone, although these cultures were not
      significantly different from one another. Cocultures at a 1:1 ratio had the best
      barrier, significantly better than all other cultures. CONCLUSIONS: Endothelial
      cell monolayers are an inadequate model of the microcirculation. As PC form a key
      component of the capillary wall in vivo and as addition of PC to MVEC monolayers
      in vitro, optimally at a 1:1 ratio, increase their barrier effect to large and
      small molecules, we believe it is necessary to include both cells in future in
      vitro studies.

PMID- 11319887
TI  - Learning curves and breast cancer lymphatic mapping: institutional volume index.
AB  - INTRODUCTION: To date, studies of breast cancer lymphatic mapping (LM) have
      analyzed success with respect to individual surgeons. However, LM and sentinel
      lymph node biopsy (SLNBx) are procedures that require institutional
      multidisciplinary cooperation between the departments of radiology, pathology,
      and surgery. Thus, it is important to evaluate these procedures with respect to
      the institution. This study examines 30 institutions to clarify the value of the
      institutional volume index (IVI) (cases/month) to the outcome of LM and SLNBx in
      breast cancer. METHODS: From July 1997 to July 1999, 30 institutions participated
      in the Department of Defense national breast LM trial. All participants underwent
      a 2-day training course for surgeons, nuclear medicine physicians, and
      pathologists. The records for each institution were prospectively accrued and
      submitted to a database. The false negatives, failure rates, and IVI were
      calculated for each institution. A logistic regression model plots the
      relationship between IVI and institutional failure rate. Using a multivariate
      analysis, mapping failure was analyzed as a function of case number with respect
      to the individual surgeon and the institution as a whole. RESULTS: False negative
      results were demonstrated in only 5 (4%) cases among all institutions and were
      excluded from further analysis due to small numbers. Mapping failures were found
      in all but 7 of the 30 institutions whose data were complete. There were 71
      mapping failures among 74 surgeons over 555 cases, which yielded an overall
      failure rate of 12.79% (71 555). The logistic regression model revealed an
      inverse relationship between IVI and institutional failure rate. However, the
      multivariate analysis revealed that the individual surgeon performance was the
      most significant factor in determining institutional mapping success. CONCLUSION:
      Failure to map can be a function of multiple factors including surgical skill,
      surgical volume index, and injection method of the SLN patient, all under the
      quality control of an institution. The surgical failure rate on the other hand is
      a function of surgical skill, surgical volume, and injection methods. While
      differences in mapping success exist across institutions, this disparity is not
      due to factors associated with the institution as a whole, but lie with the
      individual surgeon.

PMID- 11319888
TI  - Clostridium difficile toxins and enterococcal translocation in vivo and in vitro.
AB  - BACKGROUND: Clostridium difficile toxins alter permeability in cultured
      enterocytes and may alter intestinal epithelial permeability to bacteria in vivo.
      Experiments were designed to test the effects of C. difficile toxins on in vitro
      interactions of Enterococcus gallinarum with cultured enterocytes, as well as on
      translocation of E. gallinarum in mice. MATERIALS AND METHODS: Mature Caco-2 and
      HT-29 enterocytes were pretreated with C. difficile toxin A or toxin B followed
      by incubation with E. gallinarum. E. gallinarum-enterocyte interactions were
      assessed by quantitative culture. For in vivo experiments, antibiotic-treated
      mice were orally inoculated with C. difficile or saline, and all mice were orally
      inoculated 24 h later with E. gallinarum and sacrificed after another 24 h for
      analysis of cecal bacteria, cecal C. difficile toxin, and enterococcal
      translocation. Cecal C. difficile toxin was assayed as cytopathic effects on
      human foreskin fibroblasts. RESULTS: Although neither toxin had a noticeable
      effect on bacterial internalization by cultured enterocytes, C. difficile toxins
      were associated with increased E. gallinarum transmigration across confluent
      enterocyte cultures. Mice orally inoculated with saline rather than C. difficile
      (n = 29) had no detectable cecal toxin, while mice orally inoculated with C.
      difficile (n = 30) had detectable cecal toxin. Viable E. gallinarum was recovered
      from the mesenteric lymph nodes of 97% of mice orally inoculated with saline
      followed by oral E. gallinarum, but only 37% of mice orally inoculated with C.
      difficile followed by oral E. gallinarum (P < 0.01). CONCLUSIONS: These results
      suggested that observations with cultured enterocytes, demonstrating that C.
      difficile toxins facilitated bacterial migration across the intestinal
      epithelium, might have little in vivo relevance in a mouse model of antibiotic
      induced C. difficile overgrowth.

PMID- 11319889
TI  - Modeling of branching structures of plants.
AB  - Previous studies of branching structures generally focused on arteries. Four cost
      models minimizing total surface area, total volume, total drag and total power
      losses at a junction point have been proposed to study branching structures. In
      this paper, we highlight the branching structures of plants and examine which
      model fits data of branching structures of plants the best. Though the effect of
      light (e.g. phototropism) and other possible factors are not included in these
      cost models, a simple cost model with physiological significance, needs to be
      verified before further research on modeling of branching structures is
      conducted. Therefore, data are analysed in this paper to determine the best cost
      model. Branching structures of plants are studied by measuring branching angles
      and diameters of 234 junctions from four species of plants. The sample includes
      small junctions, large junctions, two- and three-dimensional junctions, junctions
      with three branches joining at a point and those with four branches joining at a
      point. First, junction exponents (x) were determined. Second, log-log plots
      indicate that model of volume minimization fits data better than other models.
      Third, one-sided t -tests were used to compare the fitness of four models. It is
      found that model of volume minimization fits data better than other cost models.

PMID- 11319890
TI  - Theory of robustness of irreversible differentiation in a stem cell system: chaos
      hypothesis.
AB  - Based on an extensive study of a dynamical systems model of the development of a
      cell society, a novel theory for stem cell differentiation and its regulation is
      proposed as the "chaos hypothesis". Two fundamental features of stem cell systems
      stochastic differentiation of stem cells and the robustness of a system due to
      regulation of this differentiation-are found to be general properties of a system
      of interacting cells exhibiting chaotic intra-cellular reaction dynamics and cell
      division, whose presence does not depend on the detail of the model. It is found
      that stem cells differentiate into other cell types stochastically due to a
      dynamical instability caused by cell-cell interactions, in a manner described by
      the Isologous Diversification theory. This developmental process is shown to be
      stable not only with respect to molecular fluctuations but also with respect to
      the removal of cells. With this developmental process, the irreversible loss of
      multipotency accompanying the change from a stem cell to a differentiated cell is
      shown to be characterized by a decrease in the chemical diversity in the cell and
      of the complexity of the cellular dynamics. The relationship between the division
      speed and the loss of multipotency is also discussed. Using our model, some
      predictions that can be tested experimentally are made for a stem cell system.

PMID- 11319891
TI  - The theory and application of transition state pK(a) values: the reaction of
      papain with a series of trimethylene disulphide reactivity probes.
AB  - For many years methods to describe the structure of the transition state for a
      reaction have been sought. Most commonly these structures have been inferred from
      kinetic isotope effects. We report here for the first time the application of
      transition state pK(a) values to describe the relationship between molecular
      recognition and the transition state for the catalytic mechanism of papain. The
      background to the theory is presented and applied to the reactions of papain with
      a series of trimethylene disulphide reactivity probes. The common feature of
      these reactions is a loss in reactivity on ionization of the imidazolium cation
      for those probes containing molecular recognition features and an increase in
      reactivity on ionization of the electrostatic switch residue. The use of
      transition state pK(a) values enhances this information by providing details
      regarding the protonic distribution within the transition state. This has led to
      the reconsideration of the effect of the electrostatic switch ionization and the
      role of the hydrogen bond formed between the catalytic-site imidazolium cation
      and the leaving group of the reaction in the catalytic mechanism of papain.

PMID- 11319892
TI  - Modelling inert gas exchange in tissue and mixed-venous blood return to the
      lungs.
AB  - Inert gas exchange in tissue has been almost exclusively modelled by using an
      ordinary differential equation. The mathematical model that is used to derive
      this ordinary differential equation assumes that the partial pressure of an inert
      gas (which is proportional to the content of that gas) is a function only of
      time. This mathematical model does not allow for spatial variations in inert gas
      partial pressure. This model is also dependent only on the ratio of blood flow to
      tissue volume, and so does not take account of the shape of the body compartment
      or of the density of the capillaries that supply blood to this tissue. The
      partial pressure of a given inert gas in mixed-venous blood flowing back to the
      lungs is calculated from this ordinary differential equation. In this study, we
      write down the partial differential equations that allow for spatial as well as
      temporal variations in inert gas partial pressure in tissue. We then solve these
      partial differential equations and compare them to the solution of the ordinary
      differential equations described above. It is found that the solution of the
      ordinary differential equation is very different from the solution of the partial
      differential equation, and so the ordinary differential equation should not be
      used if an accurate calculation of inert gas transport to tissue is required.
      Further, the solution of the PDE is dependent on the shape of the body
      compartment and on the density of the capillaries that supply blood to this
      tissue. As a result, techniques that are based on the ordinary differential
      equation to calculate the mixed-venous blood partial pressure may be in error.

PMID- 11319893
TI  - Multiple walking speed-frequency relations are predicted by constrained
      optimization.
AB  - A person constrained to walk at a given speed v on a treadmill, chooses a
      particular step frequency f and step length d=v/f. Testing over a range of speeds
      generates a speed-frequency (v-f) relationship. This relationship is commonly
      posited as a basic feature of human gait. It is often further posited that this
      curve follows from minimum energy cost strategy. We observed that individuals
      walking under different constraint circumstances--walking to a range of fixed
      metronome frequencies (fixed f) or over a range of spaced markers (fixed d)-
      produce speed-frequency relations distinct from the constrained v relation. We
      show here that three distinct speed-frequency curves, similar to those observed,
      are predicted by the assumption that a walking person optimizes an underlying
      objective function F (v, f) that has a minimum at the preferred gait. Further,
      the metabolic cost of transport is a reasonable approximate candidate for the
      function F.

PMID- 11319894
TI  - Are certain life histories particularly prone to local extinction?
AB  - Using stochastic simulations and elasticity analysis, we show that there are
      inherent differences in the risk of extinction between life histories with
      different demographies. Which life history is the most vulnerable depends on
      which vital rate varies. When juvenile survival varies semelparous organisms with
      delayed reproduction are the most vulnerable ones, while a varying developmental
      rate puts a greater threat to semelparous organisms with rapid development.
      Iteroparous organisms are the most vulnerable ones when adult survival varies.
      Generally, we do not expect to observe organisms in nature having variation in
      vital rates that produce a high risk of extinction. Given the results here we
      therefore predict that iteroparous organisms should show low variation in adult
      survival. Moreover, we predict that semelparous organisms should show low
      variation in juvenile survival and low variation in developmental rate. The
      effect of temporal correlation on extinction risk is most pronounced in organisms
      with semelparous life histories.

PMID- 11319895
TI  - A reliable and safe T cell repertoire based on low-affinity T cell receptors.
AB  - Antigens are presented to T cells as short peptides bound to MHC molecules on the
      surface of body cells. The binding between MHC/peptides and T cell receptors
      (TCRs) has a low affinity and is highly degenerate. Nevertheless, TCR-MHC/peptide
      recognition results in T cell activation of high specificity. Moreover, the
      immune system is able to mount a cellular response when only a small fraction of
      the MHC molecules on an antigen-presenting cell is occupied by foreign peptides,
      while autoimmunity remains relatively rare. We consider how to reconcile these
      seemingly contradictory facts using a quantitative model of TCR signalling and T
      cell activation. Taking into account the statistics of TCR recognition and
      antigen presentation, we show that thymic selection can produce a working T cell
      repertoire which will produce safe and effective responses, that is, recognizes
      foreign antigen presented at physiological levels while tolerating self. We
      introduce "activation curves" as a useful tool to study the repertoire's
      statistical activation properties.

PMID- 11319896
TI  - Regressive biological evolution due to environmental change.
AB  - Simulation results are presented which suggest that regressive evolution (i.e.,
      evolution to a less adapted state) often occurs in response to environmental
      change, by a process analogous to the stress-induced reversal of aging in glassy
      materials. The key to this process is the stress-induced disappearance of fitness
      optima that lead to irreversible changes in the location of a population in
      genotype space. Even though the population may always evolve to higher fitness
      states, this irreversible process will often act to bring an initially well
      adapted system to a less adapted state upon a return to initial conditions.

PMID- 11319897
TI  - Hypothesis: hemimelia and the maintenance of pentadactyly?
AB  - The limbs of extant terrestrial vertebrates possess five or fewer digits, yet,
      polydactyly is accepted as being the ancestral state. Therefore, I propose a
      hypothesis to account for the maintenance of digital number at five or fewer
      digits, based on a selective disadvantage associated with polydactylous states in
      terrestrial vertebrates. This disadvantage is not associated with the polydactyly
      per se, but rather with the hemimelia which is a common feature of polydactylies
      in mammals. Hemimelia causes a twisting, or luxation, of the distal segment of
      the limb, which is due to a malformation of the radius/tibia of the limb. This
      defect results in the limb being held in an abnormal gait, which causes problems
      in the locomotion of the animal which would compromise their ability to flourish.
      Therefore, the abnormal gait and torsion of the limb caused by the hemimelia is
      acting as a stabilizing force to maintain the dactyly of the tetrapod limb with
      five or fewer digits.

PMID- 11319898
TI  - A mathematical model for experimental gene evolution.
AB  - The purpose of this paper is to determine the optimal mutation rate for random
      mutagenesis procedures used to make mutant libraries for subsequent screening.
      When the mutation rate is low, the probability of achieving a rare beneficial
      mutation is low. When the mutation rate is high, the probability of producing
      lethal mutations which result in loss of function is also high. We demonstrate
      that between these two extremes, an optimal mutation rate exists for experimental
      gene improvement. This rate depends strongly on the number of simultaneous
      mutations required for a beneficial change of the gene, but only weakly on the
      number of possible lethal mutations. This model predicts that when mutagenesis is
      performed at the optimum mutation rate, at least 63% (1--e(-1)) of the cloned
      genes in a mutant library will be non-functional.

PMID- 11319899
TI  - Pharma + profits = continued aids epidemic.

PMID- 11319901
TI  - Correcting a deficiency.

PMID- 11319902
TI  - A death in the laboratory: the politics of the Gelsinger aftermath.

PMID- 11319903
TI  - Therapeutic efficacy of G207, a conditionally replicating herpes simplex virus
      type 1 mutant, for gallbladder carcinoma in immunocompetent hamsters.
AB  - Gallbladder cancer is an extremely difficult disease to cure once metastases
      occur. In this paper, we explored the potential of G207, an oncolytic,
      replication-competent herpes simplex virus type 1 mutant, as a new therapeutic
      means for gallbladder cancer. Gallbladder carcinoma cell lines (four human and
      one hamster) showed nearly total cell killing within 72 h of G207 infection at a
      m.o.i. of 0.25 to 2.5 in vitro. The susceptibility to G207 cytopathic activity
      correlated with the infection efficiency demonstrated by lacZ expression.
      Intraneoplastic inoculation of G207 (1 x 10(7) pfu) in immunocompetent hamsters
      bearing established subcutaneous KIGB-5 tumors caused a significant inhibition of
      tumor growth and prolongation of survival. Repeated inoculations (three times
      with 4-day intervals) were significantly more efficacious than a single
      inoculation. In hamsters with bilateral subcutaneous KIGB-5 tumors, inoculation
      of one tumor alone with G207 caused regression or growth reduction of
      uninoculated tumors as well as inoculated tumors. In athymic mice, however, the
      anti-tumor effect was largely reduced in inoculated tumors and completely
      abolished in remote tumors, suggesting large contribution of T-cell-mediated
      immune responses to both local and systemic anti-tumor effect of G207. These
      results indicate that G207 may be useful as a new strategy for gallbladder cancer
      treatment.

PMID- 11319904
TI  - Enhanced transgene expression in cord blood CD34(+)-derived hematopoietic cells,
      including developing T cells and NOD/SCID mouse repopulating cells, following
      transduction with modified trip lentiviral vectors.
AB  - The recent development of lentivirus-derived vectors is an important breakthrough
      in gene transfer technology because these vectors allow transduction of
      nondividing cells such as hematopoietic stem cells (HSC), due to an active
      nuclear import of reverse-transcribed vector DNA. We recently demonstrated that
      addition of the central DNA flap of HIV-1 to an HIV-derived lentiviral vector
      strikingly increases transduction of CD34(+) cells. We now describe improvements
      of the transduction protocol designed to preserve HSC properties and two
      modifications of the previously described TRIP-CMV vector. First, deletion of the
      enhancer/promoter of the 3' LTR in the TRIP-CMV vector resulted in a safer vector
      (TRIPDeltaU3-CMV) with conserved transduction efficiency and increased EGFP
      transgene expression. Second, the original internal CMV promoter was replaced
      with the promoter for the ubiquitously expressed elongation factor 1alpha
      (EF1alpha). This promoter substitution resulted in a significantly more
      homogeneous expression of the EGFP transgene in all hematopoietic cell types,
      including CD34(+)-derived T lymphocytes, in which the CMV promoter was inactive,
      and NOD/SCID mouse repopulating cells. We thus present here an HIV-derived
      lentiviral vector, TRIPDeltaU3-EF1alpha, which can very efficiently transduce
      human cord blood HSC and results in high long-term transgene expression in
      CD34(+)-derived T, B, NK, and myeloid hematopoietic cells.

PMID- 11319905
TI  - Exogenously regulated stem cell-mediated gene therapy for bone regeneration.
AB  - Regulated expression of transgene production and function is of great importance
      for gene therapy. Such regulation can potentially be used to monitor and control
      complex biological processes. We report here a regulated stem cell-based system
      for controlling bone regeneration, utilizing genetically engineered mesenchymal
      stem cells (MSCs) harboring a tetracycline-regulated expression vector encoding
      the osteogenic growth factor human BMP-2. We show that doxycycline (a
      tetracycline analogue) is able to control hBMP-2 expression and thus control MSC
      osteogenic differentiation both in vitro and in vivo. Following in vivo
      transplantation of genetically engineered MSCs, doxycycline administration
      controlled both bone formation and bone regeneration. Moreover, our findings
      showed increased angiogenesis accompanied by bone formation whenever genetically
      engineered MSCs were induced to express hBMP-2 in vivo. Thus, our results
      demonstrate that regulated gene expression in mesenchymal stem cells can be used
      as a means to control bone healing.

PMID- 11319906
TI  - Lipopolysaccharide potentiates the effect of hepatocyte growth factor upon
      replication in lung, thyroid, spleen, and colon in rats in vivo.
AB  - Induction of replication may potentiate in vivo gene therapy, as some viral
      vectors only transduce dividing cells. Hepatocyte growth factor (HGF) increases
      the percentage of replicating hepatocytes to 18-fold that in normal rats, and
      lipopolysaccharide (LPS) modestly potentiates this effect. In this study, the
      effect of iv HGF upon replication in other organs was determined. HGF at 10 mg/kg
      resulted in replication that was < or =3-fold that of normal rats in alveolar and
      proximal renal tubular cells. HGF alone had no effect upon replication of
      epithelial cells from the bronchi, thyroid, pancreas, or colon or upon cells from
      the muscle, pancreatic islets, spleen, blood vessels, or thymus. HGF and LPS at 5
      mg/kg resulted in replication that was 9-fold that of normal rats in alveolar
      cells, 25-fold in bronchial epithelial cells, 4-fold in thyroid epithelial cells,
      1.5-fold in the red pulp of the spleen, and 2-fold in colonic epithelial cells.
      The synergistic effect may be due to the fact that LPS upregulated the HGF
      receptor c-met in thyroid, spleen, and colon. We conclude that iv administration
      of HGF alone is relatively specific for inducing hepatocyte replication and would
      allow selective gene transfer into the liver.

PMID- 11319907
TI  - Receptor-targeted gene delivery using multivalent phagemid particles.
AB  - Although growth factor- and antibody-targeted filamentous phage have recently
      been demonstrated to transduce mammalian cells, there is a significant need to
      increase transduction efficiency so as to improve the usefulness of targeted
      phage vectors for gene therapy and ligand discovery. Here, we describe the use of
      multivalent phagemid vectors that are specifically designed for ligand-targeted
      mammalian cell transduction. This phagemid system has certain advantages over
      phage vectors, such as larger insert size and vector stability, and it retains
      the multivalent display necessary for efficient cell binding and internalization.
      Immunoblotting revealed that the most efficient multivalent display (exceeding
      that of a phage vector) was achieved in the phagemid system when epidermal growth
      factor (EGF) was fused to the C-terminal domain of the pIII coat protein. We
      compared phagemid particles displaying EGF at high or low valence by rescuing the
      vector with R408d3 (pIII deleted) or wild-type R408 helper phage, respectively.
      More efficient display of EGF correlated with increased internalization, vector
      potency, and transduction efficiency ( approximately 9%). The findings described
      here support our original hypothesis that phage-based vectors can be modified for
      more efficient gene transfer and suggest that directed evolution may be applied
      to increase their potential even further.

PMID- 11319908
TI  - Functional correction of fanconi anemia group C hematopoietic cells by the use of
      a novel lentiviral vector.
AB  - Lentiviral vectors transduce nondividing hematopoietic cells more efficiently
      than other currently available vector systems. Here we report the results of
      human hematopoietic cell gene transfer using lentiviral vectors based upon human
      immunodeficiency virus (HIV-1) and equine infectious anemia virus (EIAV). EIAV is
      a nonprimate lentivirus and is severely restricted in its host range to horses
      and closely related equines. We employed the EIAV vector system to test for gene
      transfer to human Fanconi anemia (FA) hematopoietic cells by comparison with HIV
      1- and Moloney murine leukemia virus-based systems. Fanconi anemia is
      characterized by bone marrow failure secondary to stem cell dysfunction. Fanconi
      anemia group C EBV-transformed lymphoblasts were transduced with all three viral
      vectors. Phenotypic correction of FA cells, as measured by mitomycin C drug
      resistance, was observed with a similar efficiency in all vector systems. This is
      the first description of lentiviral correction of FA cells and suggests that
      lentiviral vectors may be useful for FA gene transfer.

PMID- 11319909
TI  - Suppression of colorectal cancer growth using an adenovirus vector expressing an
      antisense K-ras RNA.
AB  - In human colorectal cancer, K-ras point mutations occur in approximately 40-50%
      of the cases, a frequency second only to pancreatic cancer (80-90%). Unlike
      pancreatic and lung cancers, however, the tumor-suppressive effect of antisense K
      ras RNA expression has not been examined for colorectal cancers. A recombinant
      adenovirus vector expressing an antisense or sense K-ras gene fragment (AxCA-AS-K
      ras or AxCA-S-K-ras) was first transduced into seven human colorectal cancer cell
      lines. Stable expression of antisense or sense K-ras RNA was detected by RNA blot
      analysis. Western blot analysis confirmed a reduction of up to 25% of K-ras
      specific p21 protein in the antisense K-ras-transduced HCT-15 cells. In contrast
      to our previous findings on pancreatic cancer, the status of K-ras point
      mutations was not correlated with the growth-suppressive effect of the antisense
      K-ras vector: both the K-ras-mutation-positive and -negative colorectal cancer
      cell lines were suppressed for their growth in vitro. There was no growth
      inhibitory effect on normal cells such as hepatocytes. Next, to test the efficacy
      in vivo, HCT-15 cells were inoculated subcutaneously into the left flank of SCID
      mice, and AxCA-AS-K-ras was injected intratumorally three times after the tumor
      mass was established. The infection of AxCA-AS-K-ras, but not the control AxCA-S
      K-ras, significantly suppressed the growth of the HCT-15 subcutaneous tumor. This
      study shows that the adenovirus-mediated in vivo gene transfer of the antisense K
      ras construct may be a useful therapeutic strategy for colorectal cancer.

PMID- 11319910
TI  - In vivo surgical resection plus adjuvant gene therapy in the treatment of mammary
      and prostate cancer.
AB  - Adenoviral-mediated gene therapy delivery, combining the herpes simplex virus
      thymidine kinase gene (Ad-tk) with gancyclovir, has been evaluated as a treatment
      modality for numerous tumors in the laboratory and in the clinics. As a single
      modality, gene therapy has shown some promising local and systemic results but no
      curative success. Surgery is the standard of care for many solid tumors. However,
      minor residual tumor following surgical resection can lead to local recurrence,
      and surgery is neither efficient nor plausible for metastatic disease. In this
      study, two tumor models were used to evaluate the effects of Ad-tk gene therapy
      as an adjuvant to surgery. Subcutaneous mammary- and prostate-derived tumors were
      produced in syngeneic mice. To evaluate systemic effects, tumor cells were
      injected intravenously, with subsequent formation of lung nodules. The
      subcutaneous tumors were surgically resected and the tumor bed was bathed with
      saline or Ad-tk. The animals were evaluated for toxicity, local tumor recurrence,
      survival, and lung nodule formation. No evidence of additional toxicity was
      observed. In the less aggressive mammary model, the time to recurrence was
      increased from 11.7 (+/-1.0) days to 22.7 (+/-5.5) days. In the prostate model,
      recurrence went from a mean of 17.3 (+/-5.6) to 22.6 (+/-6.8) days. Survival was
      also improved from a mean of 19.7 (+/-1.1) to 32.3 (+/-4.8) and 26.1 (+/-5.0) to
      34.1 (+/-6.1) days in the mammary and prostate models, respectively. Evidence of
      systemic benefits from the use of adjuvant Ad-tk therapy was demonstrated by a
      significant reduction in lung nodules from a mean of 17 to 3.5. These results
      suggest that Ad-tk gene therapy may be a useful adjuvant for patients undergoing
      surgery for treatment of cancer.

PMID- 11319911
TI  - Two animal models of retinal degeneration are rescued by recombinant adeno
      associated virus-mediated production of FGF-5 and FGF-18.
AB  - The goal of these experiments was to evaluate the potential of the fibroblast
      growth factor family members FGF-5 and FGF-18 to rescue photoreceptors from cell
      death in retinal degenerative disease. Two strains of transgenic rats, expressing
      either a P23H or an S334ter rhodopsin mutation, were used as model systems. The
      neurotrophic growth factors were delivered by subretinal injection of adeno
      associated virus vectors, driving expression of the genes with a constitutive CMV
      promoter. Morphological and functional analyses were performed to determine
      whether FGF-5 or FGF-18 overexpression could ameliorate cell death in the retina.
      Immunocytochemistry was used to determine the cellular sites of expression of the
      factors and to test for up-regulation of FGF receptors due to injection.
      Significant rescue from photoreceptor cell death was found after injections of
      vectors expressing either FGF-5 or FGF-18 in the animal models. Increased
      survival of photoreceptors did not produce a significant increase in
      electroretinographic responses, however, reflecting either trauma due to the
      surgery or a suppression of signaling due to expression of proteins. Three weeks
      after injections, both growth factors were localized to the inner and outer
      segments of photoreceptors, and the receptors FGFR1 and FGFR2 were also found to
      be up-regulated in these regions. No visible pathological changes were seen in
      the FGF-5- or FGF-18-treated eyes. These results indicate that the delivery of
      either FGF-5 or FGF-18 with adeno-associated virus protects photoreceptors from
      apoptosis in transgenic rat models of retinitis pigmentosa and that the rescue is
      probably mediated by conventional receptor tyrosine kinase pathways in
      photoreceptors.

PMID- 11319912
TI  - Factors affecting long-term expression of a secreted transgene product after
      intravenous administration of a retroviral vector.
AB  - We have studied parameters affecting in vivo expression of human growth hormone
      (hGH) in mice after intravenous administration of a retroviral vector encoding
      the protein as a model system for clotting factor VIII gene therapy. Such
      treatment results in a brief burst of high-level expression followed by lower
      level sustained expression of the hGH in the circulation. The major targets for
      transduction in the mouse are liver and spleen. Such direct transduction (i.e.,
      without surgical or chemical induction of cell division) requires vector at high
      titer (>/=10(8) cfu/ml) and is dose dependent. Transduction efficiency decreases
      with increasing age of the recipient. Nevertheless, long-term expression in
      adults is observed after administration of vector as a split dose on 2
      consecutive days. We also show that anti-vector immune responses may enhance long
      term expression and that both anti-vector and anti-transgene immunity can be
      modulated. This work provides a framework for the rational development of means
      to enhance the efficiency of retroviral vectors for use in clinical gene
      replacement therapy.

PMID- 11319913
TI  - Introduction of single base substitutions at homologous chromosomal sequences by
      adeno-associated virus vectors.
AB  - Adeno-associated virus (AAV) vectors can modify homologous chromosomal sequences
      at high rates. This gene targeting transduction pathway is distinct from the
      integrating and episomal pathways used in gene addition approaches. In previous
      studies, AAV vectors were used to introduce small insertion and deletion
      mutations at homologous chromosomal loci. Here we show that AAV-mediated gene
      targeting can also be used to introduce all possible types of single base
      substitution mutations at the endogenous single-copy hypoxanthine phosphoribosyl
      transferase locus. Southern blot and sequence analysis showed that the point
      mutations were introduced with high fidelity. We also show that AAV vectors can
      repair chromosomal alkaline phosphatase genes containing point mutations. Our
      results suggest that AAV vectors can be used to introduce single base
      substitutions at high frequencies in normal human cells, including the correction
      of point mutations responsible for genetic diseases.

PMID- 11319914
TI  - Smaller amounts of antiretroviral drugs are needed when combined with an active
      ribozyme against HIV-1.
AB  - We have tested for combined anti-HIV-1 effects of a hammerhead ribozyme and
      antiretroviral drugs and the possibility of reducing the drug burden of patients
      on highly active antiretroviral therapy (HAART). The antiretroviral compounds
      used represent the three groups in HAART: nucleoside analogue reverse
      transcriptase inhibitors, nonnucleoside reverse-transcriptase inhibitors, and
      protease inhibitors. A human T cell line (HUT78), stably expressing a hammerhead
      ribozyme targeted to nef (hhRz.nef(9016-9029)), was infected with HIV-1(SF2) in
      the presence of a single drug. The combined effects on HIV-1 replication were
      measured by p24 antigen determinations over a 2-week period. In the presence of
      the ribozyme, smaller amounts of antiretroviral drugs were required to reduce the
      HIV-1 p24 levels equally as much as when only drugs were present. The results
      support a strategy of combining ribozyme gene therapy with HAART to improve the
      long-term outcome of anti-HIV-1 therapy.

PMID- 11319915
TI  - Enhanced therapeutic effect of HSV-tk+GCV gene therapy and ionizing radiation for
      prostate cancer.
AB  - Standard therapies for prostate cancer including radiation, prostatectomy, and
      hormone ablation have significant toxicities and recurrence risk. HSV-tk gene
      therapy may be effective in combination with radiation therapy due to
      complementary mechanisms and distinct toxicity profiles. Mouse prostate tumors
      transplanted subcutaneously were treated by either gene therapy involving
      intratumoral injection of AdV-tk followed by systemic ganciclovir or local
      radiation therapy or the combination of gene and radiation therapy. Both single
      therapy modalities showed a 38% decrease in tumor growth compared to controls.
      The combined treatment resulted in a decrease of 61%. In addition the combined
      therapy group had a mean survival of 22 days versus 16.6 days for single therapy
      and 13.8 days for nontreated controls. To analyze systemic anti-tumor activity,
      lung metastases were generated by tail vein injection of RM-1 prostate cancer
      cells on the same day that they were injected subcutaneously. The primary tumors
      were treated as before with AdV-tk followed by ganciclovir, radiation, or the
      combination. The number of lung nodules was reduced by 37% following treatment
      with AdV-tk, whereas radiotherapy alone had no effect on metastatic growth. The
      combination led to an additional 50% reduction in lung colonization. Primary
      tumors that received the combination therapy had a marked increase in CD4 T cell
      infiltrate. This is the first report showing a dramatic systemic effect following
      the local combination treatment of radiation and AdV-tk. A clinical study using
      this strategy has been initiated and patient accrual is ongoing.

PMID- 11319917
TI  - Transgene expression in mouse airway epithelium by aerosol gene therapy with PEI
      DNA complexes.
AB  - Gene therapy targeted at the respiratory epithelium holds therapeutic potential
      for diseases such as cystic fibrosis and alpha-1 anti-trypsin deficiency. A
      variety of approaches such as intranasal or intratracheal instillation and
      aerosol delivery have been utilized to target genes to the airways.
      Polyethylenimine (PEI), a linear or branched polycationic polymer, has been used
      for delivery of genes to various organs. In this study, using fluorescein
      isothiocyanate (FITC)-labeled branched PEI, we initially examined the
      localization of PEI in the lungs after aerosol delivery to Balb/C mice. Further,
      after aerosol delivery of PEI-CAT DNA, in situ immunostaining for chloramphenicol
      acetyl transferase (CAT) protein was used to localize the transgene expression
      within the lungs. Immunohistochemistry for CAT, as well as localization of FITC
      labeled PEI, revealed that after aerosol delivery, the PEI-DNA complexes deposit
      and subsequently transfect most of the epithelial cells in the conducting airways
      (including the peripheral airways). High levels of CAT were detected at 24 h
      after aerosol exposure and significant CAT expression was detected in the lungs
      up to 28 days after a single aerosol exposure. The data suggest that aerosol
      delivery of PEI-DNA complexes could be effective for the treatment of pulmonary
      diseases such as cystic fibrosis and alpha-1 anti-trypsin deficiency.

PMID- 11319916
TI  - Bone-directed expression of Col1a1 promoter-driven self-inactivating retroviral
      vector in bone marrow cells and transgenic mice.
AB  - Gene therapy of bone would benefit from the availability of vectors that provide
      stable, osteoblast-specific expression. This would allow bone-specific expression
      of Col1a1 cDNAs for treatment of osteogenesis imperfecta. In addition, such a
      vector would restrict expression of secreted therapeutic proteins to the bone
      synthesizing regions of the bone marrow after ex vivo transduction of marrow
      stromal cells and reintroduction of the cells into patients. Retrovirus vectors
      stably integrate into target cell genomes; however, long-term regulated
      expression from internal cellular promoters has not been consistently achieved.
      In some cases this is due to a stem cell-specific mechanism for transcriptional
      repression of retroviruses. We evaluated the ability of self-inactivating ROSA
      derived vectors containing a bone-directed 2.3-kb rat Col1a1 promoter to display
      osteoblast-specific expression. In vitro expression was examined in bone marrow
      stromal cell cultures induced to undergo osteoblastic differentiation. In vivo
      expression was evaluated in chimeric mice derived from transduced embryonic stem
      cells. The results indicate that self-inactivating retrovirus vectors containing
      the Col1a1 promoter are not permanently inactivated in embryonic stem cells and
      are specifically expressed in osteoblasts in vivo and in vitro. Thus these
      vectors should be useful for bone-directed gene therapy.

PMID- 11319918
TI  - Direct exposure of mouse ovaries and oocytes to high doses of an adenovirus gene
      therapy vector fails to lead to germ cell transduction.
AB  - The risk of insertion of adenovirus gene therapy DNA into female germ cells
      during the course of somatic gene therapy was stringently tested in the mouse by
      injecting up to 10(10) infectious particles directly into the ovary and by
      incubating naked oocytes in a solution of 2 x 10(8) particles/ml for 1 h prior to
      in vitro fertilization (IVF). The vector used was a recombinant adenovirus
      carrying the bacterial lacZ gene driven by the cytomegalovirus promoter (Adbeta
      gal). Ovaries were stained for LacZ activity, or immunochemically for LacZ, 5-7
      days after injection. Although very large amounts of LacZ activity and protein
      were detected, all positive staining was in the thecal portion of the ovary, with
      no staining seen in oocytes. In another series of experiments, mice with injected
      ovaries were mated, and preimplantation embryos or fetuses were analyzed either
      for LacZ expression or by PCR for lacZ DNA. None of 202 preimplantation embryos
      stained positively for LacZ and none of 58 fetuses were positive for DNA by PCR
      analysis. Finally, more than 1400 eggs were fertilized after exposure to the
      vector prior to IVF and stained as morulae for LacZ activity. Fewer than 2% of
      the embryos stained positively for LacZ, and experiments indicated that the
      staining was due to incomplete washing of the eggs prior to IVF. These data
      provide strong evidence that adenoviruses cannot infect oocytes and that the risk
      of female germ-line transduction with such vectors is very low.

PMID- 11319919
TI  - Comparison of five retrovirus vectors containing the human IL-2 receptor gamma
      chain gene for their ability to restore T and B lymphocytes in the X-linked
      severe combined immunodeficiency mouse model.
AB  - X-linked severe combined immunodeficiency (XSCID) is caused by mutations in the
      IL-2 receptor gamma chain (IL2RG) gene, resulting in absent T lymphocytes and
      nonfunctional B lymphocytes. Recently T lymphocyte production and B lymphocyte
      function were restored in XSCID patients infused with autologous stem cells
      transduced with a retrovirus containing the human IL2RG cDNA. To optimize the
      expression of human IL2RG for future clinical trials, we compared five retroviral
      vectors expressing human IL2RG from different LTR enhancer-promoter elements in a
      mouse model. Northern and Southern blot analysis of hematopoietic tissues from
      repopulated mice revealed that the retroviral vector with the highest expression
      per copy number was MFG-S-hIL2RG, followed by MND-hIL2RG. All five vectors were
      capable of restoring lymphopoiesis in irradiated XSCID mice transplanted with
      transduced IL2RG-deficient hematopoietic stem cells. Transduction of IL2RG
      deficient hematopoietic stem cells with all five vectors restored T lymphopoiesis
      in transplanted stem cell-deficient W/W(v) mouse recipients. However, only XSCID
      stem cells transduced with the MFG-S-hIL2RG vector generated B lymphocytes in
      W/W(v) mice. We conclude that the MFG-S-hIL2RG vector provides the best
      opportunity for in vivo selection and development of B and T lymphocytes for
      human XSCID gene therapy.

PMID- 11319920
TI  - Gene therapy for the treatment of hemophilia B using PINC-formulated plasmid
      delivered to muscle with electroporation.
AB  - Gene therapy, as a safe and efficacious treatment or prevention of diseases, is
      one of the next fundamental medical innovations. Direct injection of plasmid into
      skeletal muscle is still a relatively inefficient and highly variable method of
      gene transfer. However, published reports have shown that application of an
      electric field to the muscle immediately after plasmid injection increases gene
      expression at least 2 orders of magnitude. Using this methodology, we have
      achieved potentially therapeutic circulating levels of human factor IX (hF.IX) in
      mice and dogs. A plasmid encoding hF.IX formulated with a protective,
      interactive, noncondensing (PINC) polymer was injected into the skeletal muscle
      followed by administration of multiple electrical pulses (electroporation). In
      mice long-term expression was achieved and the ability to readminister formulated
      plasmid was demonstrated. In normal dogs, expression of hF.IX reached 0.5-1.0% of
      normal levels. The transient response in dogs was due to the development of
      antibodies against hF.IX. Elevated circulating creatine kinase levels and
      histological examination indicated transient minor trauma associated with the
      procedure. These data show that gene delivery using a plasmid formulated with a
      PINC polymer augmented with electroporation is scalable into large animal models
      and represents a promising approach for treating patients with hemophilia B.

PMID- 11319921
TI  - Auto-regulated hepatic insulin gene expression in type 1 diabetic rats.
AB  - Paradigms of insulin gene therapy for type 1 diabetes should incorporate vigorous
      control for insulin gene expression to be effective in correcting postprandial
      hyperglycemia and to be safe in preventing fasting hypoglycemia. We hypothesize
      that hepatic insulin gene expression auto-regulated positively by glucose and
      negatively by insulin might be both effective and safe in the treatment of type 1
      diabetes. Expression of the glucose 6-phosphatase (G6Pase) gene in the liver is
      both stimulated by glucose and suppressed by insulin. The G6Pase promoter
      incorporated with intronic enhancers of the aldolase B gene was used to direct
      insulin gene expression in the liver of streptozotocin-induced diabetic nude
      rats. In the treated animals, blood insulin levels were elevated after feeding,
      and nonfasting hyperglycemia was significantly reduced. Glucose tolerance testing
      also illustrated that the treated animals exhibited accelerated glucose
      utilization rates. Upon fasting, blood glucose was reduced to normoglycemic range
      within 4 h and maintained at that level during the prolonged fasting of 16 h. No
      hypoglycemia was observed in any treated animals at any time throughout the
      fasting period, as blood insulin gradually declined to the normal range. These
      results suggest that auto-regulated hepatic insulin expression can potentially be
      developed as an effective and safe treatment modality for type 1 diabetes.

PMID- 11319922
TI  - Improved helper virus-free packaging system for HSV amplicon vectors using an
      ICP27-deleted, oversized HSV-1 DNA in a bacterial artificial chromosome.
AB  - Herpes simplex virus type 1 (HSV-1) amplicons are prokaryotic plasmids containing
      one or more transcriptional units and two cis-acting HSV-1 sequences: a viral
      origin of DNA replication and a viral DNA cleavage/packaging signal. In the
      presence of HSV-1 "helper" functions, amplicons are replicated and packaged into
      HSV-1 virions. Despite recent improvements in packaging methods, stocks of
      amplicon vectors are still contaminated with replication-competent helper virus
      at a frequency of 10(-4)-10(-6). To overcome this problem, we report that: (i)
      genetic modifications of HSV-1 genomes can be routinely achieved in Escherichia
      coli, either by homologous or site-specific recombination, (ii) a novel HSV-1
      bacterial artificial chromosome (fHSVDeltapacDelta27 0+), which has a deletion in
      the essential gene encoding ICP27 and an addition of ICP0 "stuffer" sequences to
      increase its size to 178 kb, supports the replication and packaging of
      cotransfected amplicon DNA without generating replication-competent helper virus
      (<1 helper virus per 10(8) TU amplicon vectors), and (iii) the resulting amplicon
      stocks have titers of up to 3-10 x 10(8) TU/ml after concentration. Elimination
      of replication-competent helper virus from HSV-1 amplicon vector stocks further
      improves safety in gene transfer applications.

PMID- 11319923
TI  - Generation of a flexible cell line with regulatable, high-level expression of HIV
      Gag/Pol particles capable of packaging HIV-derived vectors.
AB  - HIV-derived vectors are of potential clinical relevance due to their ability to
      transduce nondividing cells in vitro and in vivo. However, the generation of cell
      lines stably and reproducibly expressing high amounts of defined subviral
      particles, capable of packaging and transducing HIV-derived vectors, has been
      hampered by the cytotoxicity of some of the required gene products, in particular
      of the HIV-1 protease. The successful use of regulatable gene expression systems
      to overcome this problem requires that the remaining basally expressed gene
      product activity is below the threshold for cytotoxicity. To try to achieve this,
      we have consecutively introduced appropriate plasmids, encoding HIV rev and HIV
      gag/pol gene products, each under the control of separate ecdysone-inducible
      promoters, into human 293 cells. Using a protocol in which a specific HIV
      protease inhibitor, Saquinavir, was continuously present in the culture medium
      during selection, we could generate stable cell lines inducibly expressing high
      amounts of subviral particles. A cell line, termed 293-Rev/Gag/Pol(i), which has
      been characterized in more detail, inducibly releases, within 48 h postinduction,
      high amounts of HIV Gag/Pol particles (about 10 microg CA/ml). These HIV Gag/Pol
      particles can package and transduce third-generation HIV vectors to high titers.
      Thus, in addition to other applications, the 293-Rev/Gag/Pol(i) cell line
      represents a "founder" packaging cell line which, depending on the requirement,
      can be further modified to include specific transgene-encoding vector and
      targeting glycoprotein genes.

PMID- 11319924
TI  - A Cre-expressing cell line and an E1/E2a double-deleted virus for preparation of
      helper-dependent adenovirus vector.
AB  - Adenoviral vectors are attractive for the delivery of transgenes into mammalian
      cells because of their efficient transduction, high titer, and stability. The
      major concerns with using E1-deleted adenoviral vectors in gene therapy are the
      pathogenic potential of the virus backbone and the leaky viral protein synthesis
      that leads to host immune responses and a short duration of transgene expression.
      Helper-dependent (HD) adenoviral vectors that are devoid of all viral protein
      coding sequences have significantly increased the safety and reduced the
      immunogenicity of these vectors. Currently available HD vectors depend on an E1
      deleted adenovirus as a helper to provide viral proteins in trans. As a
      consequence, contamination with helper virus cannot be avoided in the HD vector
      preparation though it can be decreased to 0.01% using a Cre/loxP mechanism. Since
      the presence of E1-deleted helper virus may have substantial unwanted effects, we
      have developed a new Cre-expressing cell line based on an E1- and E2a
      complementing cell. This new cell line can efficiently cleave the packaging
      region in the helper virus genome. We have also developed an E1 and E2a double
      deleted helper virus. By using the CreE cell with the helper virus deleted in
      both the E1 and the E2a genes it may be possible to further improve the safety of
      the vectors.

PMID- 11319925
TI  - Streptavidin paramagnetic particles provide a choice of three affinity-based
      capture and magnetic concentration strategies for retroviral vectors.
AB  - Three strategies have been designed to concentrate infectious retroviral vectors
      from the supernatants of human- (HT1080) and murine- (NIH 3T3) based packaging
      cells. Streptavidin-conjugated paramagnetic particles in conjunction with (i)
      antibodies directed against murine fibronectin, (ii) biotinylated lectins, or
      (iii) biotin-modified packaging cell-surface proteins allow affinity-mediated
      magnetic concentration of retroviral vectors. Retroviral titers (assayed by
      colony formation of human myeloid K562 cells) are increased by 1-4 x 10(3)-fold
      after volume reductions of only 125-fold. Using these procedures, preparations of
      5 x 10(8) cfu/ml are routinely made from relatively low-titer (2-5 x 10(5)
      cfu/ml) starting material. High-titer (paramagnetic) retroviral vector
      preparations can be used for magnetic field-dependent retroviral infection in
      vitro. Magnetic field-dependent localization such as this may enable the in vivo
      administration of formulations that concentrate retroviral infection to the
      required target tissues and organs.

PMID- 11319926
TI  - Characterization of cis-acting sequences involved in canine adenovirus packaging.
AB  - The cis-acting packaging domain in adenovirus serotype 5 (Ad5) is a series of
      redundant, albeit not functionally equivalent, "A-repeats" made up of the
      consensus sequence 5'-TTTGN(8)CG-3'. A-repeats may bind trans-acting factors that
      direct packaging of the adenovirus genome into the preformed capsid. To try to
      understand this basic mechanism, we examined the packaging domain from a nonhuman
      adenovirus. We delimited the canine adenovirus type 2 (CAV-2) packaging domain to
      within 156 bp via a conditional mutation based on the Cre/loxP excision. Using an
      insertion, deletion, and substitution strategy, we generated packaging-defective
      CAV-2 vectors. Our results demonstrate that, like Ad5, CAV-2 cis-acting packaging
      sequences are located near the left inverted terminal repeat and are redundant,
      but not functionally equivalent. However, the bipartite motif found in Ad5 is
      present only once in CAV-2 and deletion of it caused only a minor variation in
      the packaging efficiency. We have identified at least four functional cis-acting
      packaging sequences in CAV-2. The CAV-2 vectors that we generated were not
      replication-defective in an E1-transcomplementing cell line and as heat stable as
      the parental vectors that did not contain mutations.

PMID- 11319927
TI  - The plasmid status of satellite bacteriophage P4.
AB  - P4 is a natural phasmid (phage-plasmid) that exploits different modes of
      propagation in its host Escherichia coli. Extracellularly, P4 is a virion, with a
      tailed icosahedral head, which encapsidates the 11.6-kb-long double-stranded DNA
      genome. After infection of the E. coli host, P4 DNA can integrate into the
      bacterial chromosome and be maintained in a repressed state (lysogeny).
      Alternatively, P4 can replicate as a free DNA molecule; this leads to either the
      lytic cycle or the plasmid state, depending on the presence or absence of the
      genome of a helper phage P2 in the E. coli host. As a phage, P4 is thus a
      satellite of P2 phage, depending on the helper genes for all the morphogenetic
      functions, whereas for all its episomal functions (integration and immunity,
      multicopy plasmid replication) P4 is completely autonomous from the helper.
      Replication of P4 DNA depends on its alpha protein, a multifunctional polypeptide
      that exhibits primase and helicase activity and binds specifically the P4 origin.
      Replication starts from a unique point, ori1, and proceeds bidirectionally in a
      straight theta-type mode. P4 negatively regulates the plasmid copy number at
      several levels. An unusual mechanism of copy number control is based on protein
      protein interaction: the P4-encoded Cnr protein interacts with the alpha gene
      product, inhibiting its replication potential. Furthermore, expression of the
      replication genes cnr and alpha is regulated in a complex way that involves
      modulation of promoter activity by positive and negative factors and multiple
      mechanisms of transcription elongation-termination control. Thus, the relatively
      small P4 genome encodes mostly regulatory functions, required for its propagation
      both as an episomal element and as a temperate satellite phage. Plasmids that,
      like P4, propagate horizontally via a specific transduction mechanism have also
      been found in the Archaea. The presence of P4-like prophages or cryptic prophages
      often associated with accessory bacterial functions attests to the contribution
      of satellite phages to bacterial evolution.

PMID- 11319928
TI  - Comparative sequence analysis of plasmids pME2001 and pME2200 of
      methanothermobacter marburgensis strains Marburg and ZH3.
AB  - Comparison of the updated complete nucleotide sequences of the two related
      plasmids pME2001 and pME2200 from the thermophilic archaeon Methanothermobacter
      marburgensis (formerly Methanobacterium thermoautotrophicum) strains Marburg and
      ZH3, respectively, revealed an almost identical common backbone structure and
      five plasmid-specific inserted fragments (IFs), four of which are flanked by
      perfect or nearly perfect direct repeats 25-52 bp in length. A 4354-bp minimal
      replicon was derived from the alignment of the two plasmids, which encodes one
      putative antisense RNA related to replication control and five open reading
      frames (ORFs) organized in two operons. The first operon consists of four ORFs,
      the third of which, i.e. ORF3, contains a helix-turn-helix motif and a purine NTP
      binding motif often found in proteins involved in DNA metabolic processes. The
      database search results suggest that ORF3 might function as a replication
      initiator protein. The large putative Rep protein encoded by pME2001 was
      overexpressed in Escherichia coli as an N-terminal His-tagged version using
      pET28a and a compatible helper plasmid that coexpresses minor tRNAs, argU and
      ileX to compensate for codon usage difference. ORFs 1, 2, and 3 are organized in
      a sequence reminiscent of that described in E. coli plasmids of the R1 family,
      cop-tap-rep. ORF6 encoded by IF1, one of the pME2200-specific elements, showed
      significant similarity to ORF6 encoded by archaeal phage psiM2 of M. marburgensis
      strain Marburg and may confer the apparent immunity of its host strain ZH3 to
      infection by phage psiM2. Our data indicate that M. marburgensis plasmids may
      evolve by a series of gene duplication and excision events.

PMID- 11319929
TI  - Construction of a new integration vector for use in Streptococcus mutans.
AB  - A new integration vector, pBGK, was constructed for delivery of heterologous DNA
      into the chromosome of Streptococcus mutans. A kanamycin resistance element
      (OmegaKm), which is flanked by transcriptional and translational terminators and
      which is selectable in both Escherichia coli and streptococci, was inserted into
      a 2.4-kb EcoRI fragment carrying the S. mutans gtfA gene. A unique SmaI site
      flanking OmegaKm is available for cloning of promoter:reporter gene fusions or
      foreign genes, which can then be integrated into the S. mutans chromosome by
      allelic exchange with the gtfA gene. The vector was used to analyze the activity
      of an S. mutans promoter by fusing it to a chloramphenicol acetyltransferase
      gene. The reporter fusions could readily be cloned into the vector at a unique
      SmaI site and the vector and passenger DNA were stable in E. coli. DNAs flanked
      by gtfA sequees integrated efficiently into the chromosome of S. mutans and were
      stably maintained in the absence of selective pressure. Expression levels of the
      reporter gene were consistent regardless of orientation or repeated subculturing.

PMID- 11319930
TI  - A simple method to construct T-vectors using XcmI cassettes amplified by
      nonspecific PCR.
AB  - Polymerase chain reaction (PCR) is one of the most powerful tools in cloning
      genes. For the direct cloning of PCR products, T-vectors, which contain
      complementary 3'-thymidine overhangs, are widely used. In the present study, we
      developed a plasmid, pNB-T, which was constructed by cloning an XcmI cassette
      with a sufficient length of DNA (over 500 bp long) between two XcmI restriction
      sites into pBluescript SK(+). An XcmI cassette was made by nonspecific PCR using
      a primer containing recognition sequences of XcmI so that pNB-T can easily be
      converted into a T-vector by restriction of the plasmid with XcmI. In addition,
      the recognition sequences for BamHI and NcoI were added at 5'-end of the primer
      in order to facilitate subcloning of the gene cloned in the T-vector. The cloning
      efficiency of a PCR product, the glyceraldehyde-3-phosphate dehydrogenase (GAPDH)
      gene, was approximately 90%. Digestion of the recombinant plasmid containing the
      GAPDH gene with BamHI or NcoI liberated the DNA fragments with the expected size,
      demonstrating the usefulness of extra restriction sites. The method described in
      this report is quite simple and enables us to construct a variety of useful T
      vectors.

PMID- 11319931
TI  - Transfer region of a bacteroides conjugative transposon, CTnDOT.
AB  - Bacteroides species harbor large self-transmissible integrated elements called
      conjugative transposons (CTns). In this paper, we report the first complete
      sequence analysis of the transfer region of a Bacteroides CTn. The transfer
      region contained 17 genes (designated orfA-orfQ). Only 2 of the genes shared
      sequence similarity with genes in the databases and only 1 of these genes was
      associated with self-transmissible elements.

PMID- 11319932
TI  - Sequencing and analysis of the Edwardsiella ictaluri plasmids.
AB  - To determine possible functions of the Edwardsiella ictaluri plasmids, pEI1 and
      pEI2, we analyzed the sequence of both plasmids. Plasmid pEI1 is 4807 bp, with
      51% G + C, and 23 possible open reading frames of 40 amino acids or greater.
      Plasmid pEI2 is 5643 bp, with 51% G + C, and 24 possible reading frames. Database
      searches indicated that pEI1 contains an insertion element and a ROM analog. In
      addition, pEI1 possesses an open reading frame with strong homology to SlrP,
      SspH1, and SspH2 of Salmonella typhimurium and IpaH of Shigella flexnari, which
      have leucine-rich repeat regions and are components of type III secretory
      systems. pEI2 has a frame with weak homology to Spa15 of S. flexnari 5 and InvB
      of S. sonnei and S. typhimurium, which are also type III secretory system
      components, three origins of replication, a Rep analog, and a multimer resolution
      site.

PMID- 11319933
TI  - The Enterococcus faecalis pheromone-responsive plasmid pAM373 does not encode an
      entry exclusion function.
AB  - pAM373 is a conjugative plasmid in Enterococcus faecalis that confers a mating
      response to the peptide sex pheromone cAM373 which is produced also by
      Staphylococcus aureus and Streptococcus gordonii. Unlike other sex pheromone
      inducible plasmids, pAM373 does not confer an entry exclusion phenotype.

PMID- 11319934
TI  - Quantification of the differences in electromyographic activity magnitude between
      the upper and lower portions of the rectus abdominis muscle during selected trunk
      exercises.
AB  - BACKGROUND AND PURPOSE: Controversy exists around exercises and clinical tests
      that attempt to differentially activate the upper or lower portions of the rectus
      abdominis muscle. The purpose of this study was to assess the activation of the
      upper and lower portions of the rectus abdominis muscle during a variety of
      abdominal muscle contractions. SUBJECTS: Subjects (N = 11) were selected from a
      university population for athletic ability and low subcutaneous fat to optimize
      electromyographic (EMG) signal collection. METHODS: Controlling for spine
      curvature, range of motion, and posture (and, therefore, muscle length), EMG
      activity of the external oblique muscle and upper and lower portions of rectus
      abdominis muscle was measured during the isometric portion of curl-ups, abdominal
      muscle lifts, leg raises, and restricted or attempted leg raises and curl-ups. A
      one-way repeated-measures analysis of variance was used to test for differences
      in activity between exercises in the external oblique and rectus abdominis
      muscles as well as between the portions of the rectus abdominis muscle. RESULTS:
      No differences in muscle activity were found between the upper and lower portions
      of the rectus abdominis muscle within and between exercises. External oblique
      muscle activity, however, showed differences between exercises. DISCUSSION AND
      CONCLUSION: Normalizing the EMG signal led the authors to believe that the
      differences between the portions of the rectus abdominis muscle are small and may
      lack clinical or therapeutic relevance.

PMID- 11319935
TI  - Maximum voluntary activation in nonfatigued and fatigued muscle of young and
      elderly individuals.
AB  - BACKGROUND AND PURPOSE: Researchers studying central activation of muscles in
      elderly subjects (> or = 65 years of age) have investigated activation in only
      the nonfatigued state. This study examined the ability of young and elderly
      people to activate their quadriceps femoris muscles voluntarily under both
      fatigued and nonfatigued conditions to determine the effect of central activation
      failure on age-related loss of force. SUBJECTS AND METHODS: Twenty young subjects
      (11 men, 9 women; mean age = 22.67 years, SD = 4.14, range = 18-32 years) and 17
      elderly subjects (8 men, 9 women; mean age = 71.5 years, SD = 5.85, range = 65-84
      years) participated in this study. Subjects were seated on a dynamometer and
      stabilized. Central activation was quantified, based on the change in force
      produced by a 100-Hz, 12-pulse electrical train that was delivered during a 3- to
      5-second isometric maximum voluntary contraction (MVC) of the quadriceps femoris
      muscle. Next, subjects performed 25 MVCs (a 5-second contraction with 2 seconds
      of rest) to fatigue the muscle. During the last MVC, central activation was
      measured again. RESULTS: In the nonfatigued state, elderly subjects had lower
      central activation than younger subjects. In the fatigued state, this difference
      became larger. DISCUSSION AND CONCLUSION: Central activation of the quadriceps
      femoris muscle in elderly subjects was reduced in both the fatigued and
      nonfatigued states when compared with young subjects. Some part of age-related
      weakness, therefore, may be attributed to failure of central activation in both
      the fatigued and nonfatigued states.

PMID- 11319936
TI  - The effect of duration of stretching of the hamstring muscle group for increasing
      range of motion in people aged 65 years or older.
AB  - BACKGROUND AND PURPOSE: Stretching protocols for elderly people (> or = 65 years
      of age) have not been studied to determine the effectiveness of increasing range
      of motion (ROM). The purpose of this study was to determine which of 3 durations
      of stretches would produce and maintain the greatest gains in knee extension ROM
      with the femur held at 90 degrees of hip flexion in a group of elderly
      individuals. SUBJECTS: Sixty-two subjects (mean age = 84.7 years, SD = 5.6, range
      = 65-97) with tight hamstring muscles (defined as the inability to extend the
      knee to less than 20 degrees of knee flexion) participated. Subjects were
      recruited from a retirement housing complex and were independent in activities of
      daily living. METHODS: Subjects were randomly assigned to 1 of 4 groups and
      completed a physical activity questionnaire. The subjects in group 1 (n = 13,
      mean age = 85.1 years, SD = 6.4, range = 70-97), a control group, performed no
      stretching. The randomly selected right or left limb of subjects in group 2 (n =
      17, mean age = 85.5 years, SD = 4.5, range = 80-93), group 3 (n = 15, mean age =
      85.2 years, SD = 6.5, range = 65-92), and group 4 (n = 17, mean age = 83.2 years,
      SD = 4.6, range = 68-90) was stretched 5 times per week for 6 weeks for 15, 30,
      and 60 seconds, respectively. Range of motion was measured once a week for 10
      weeks to determine the treatment and residual effects. Data were analyzed using a
      growth curve model. RESULTS: A 60-second stretch produced a greater rate of gains
      in ROM (60-second stretch = 2.4 degrees per week, 30-second stretch = 1.3 degrees
      per week, 15-second stretch = 0.6 degrees per week), which persisted longer than
      the gains in any other group (group 4 still had 5.4 degrees more ROM 4 weeks
      after treatment than at pretest as compared with 0.7 degrees and 0.8 degrees for
      groups 2 and 3, respectively). DISCUSSION AND CONCLUSION: Longer hold times
      during stretching of the hamstring muscles resulted in a greater rate of gains in
      ROM and a more sustained increase in ROM in elderly subjects. These results may
      differ from those of studies performed with younger populations because of age
      related physiologic changes.

PMID- 11319937
TI  - Patient participation in physical therapy goal setting.
AB  - BACKGROUND AND PURPOSE: An important part of treatment planning in physical
      therapy is effective goal setting. The Guide to Physical Therapist Practice
      recommends that therapists should identify the patient's goals and objectives
      during the initial examination in order to maximize outcomes. The purpose of this
      study was to examine whether therapists seek to involve patients in goal setting
      and, if so, what methods they use. Therapists' attitudes toward participation and
      patient satisfaction with the examination were also examined. SUBJECTS AND
      METHODS: Twenty-two physical therapists audiotaped the initial examination of 73
      elderly patients (mean of 76.4 years of age, SD = 7.1, range = 65-94). The
      audiotaped examinations were then scored using the Participation Method
      Assessment Instrument (PMAI) to determine the frequency of attempts made by
      therapists to involve patients in goal setting. Therapists and patients completed
      surveys following the examinations. RESULTS: Therapists' use of participation
      methods during examinations ranged from a minimum of 1 to a maximum of 19 out of
      21 possible items on the PMAI. The therapists stated that they believed that it
      is important to include patients in goal-setting activities and that outcomes
      will be improved if patients participate. Patients also indicated that
      participation is important to them. DISCUSSION AND CONCLUSION: In most cases, the
      therapists did not fully take advantage of the potential for patient
      participation in goal setting. Patient and therapist education is needed
      regarding methods for patient participation during initial goal-setting
      activities.

PMID- 11319938
TI  - Changes in attitudes and perceptions about research in physical therapy among
      professional physical therapist students and new graduates.
AB  - BACKGROUND AND PURPOSE: The physical therapy profession, through its published
      educational accreditation standards and its normative model of professional
      education, has addressed the importance of educating physical therapist students
      in the basic principles and application of research. The purpose of this study
      was to conduct a longitudinal study of students relative to (1) their perception
      of knowledge with respect to research, (2) their perception of what source should
      be used (evidence-based practice or traditional protocols) for clinical decision
      making, and (3) their perception of what should be used in a clinical setting for
      patient management. SUBJECTS: Thirty-six students during the final year of their
      professional program from a sample of 115 physical therapist students who
      requested 2 consecutive physical therapist classes completed the entire sequence
      of pretest and posttest survey administrations. Seventy-nine students did not
      complete the entire sequence. METHODS: A 10-item 5-point Likert-type
      questionnaire was designed by the authors to probe the students' attitudes and
      perceptions about research, their level of comfort and confidence in reading and
      applying research findings published in the literature, and their personal habits
      regarding reading the professional literature. An expert panel consisting of
      internal and external reviewers was used for construction of the questionnaire.
      The questionnaire was completed by the students immediately preceding their
      research methods course, immediately after the completion of that course, and
      following the second research course, which included statistics and development
      of a research proposal. The subjects also completed the questionnaire after 1
      year of physical therapy practice. Friedman's analysis of variance was used as an
      omnibus test to detect differences across time. In addition, a follow-up analysis
      using the Wilcoxon signed-rank procedure to examine differences between baseline
      data and data obtained during each follow-up was done for all items to determine
      whether a difference occurred at a time other than at the final posttest survey
      administration. RESULTS: The students showed differences on 5 of the 10 items on
      the questionnaire during the study. DISCUSSION AND CONCLUSION: These items
      related to reading peer-reviewed professional journals, critically reading
      professional literature, relevance and importance of evidence-based clinical
      practice, and level of comfort with knowledge in research.

PMID- 11319939
TI  - Using published evidence to guide the examination of the sacroiliac joint region.

PMID- 11319940
TI  - Management of low back pain.

PMID- 11319941
TI  - Complex trait analysis of the mouse striatum: independent QTLs modulate volume
      and neuron number.
AB  - BACKGROUND: The striatum plays a pivotal role in modulating motor activity and
      higher cognitive function. We analyzed variation in striatal volume and neuron
      number in mice and initiated a complex trait analysis to discover polymorphic
      genes that modulate the structure of the basal ganglia. RESULTS: Brain weight,
      brain and striatal volume, neuron-packing density and number were estimated
      bilaterally using unbiased stereological procedures in five inbred strains (A/J,
      C57BL/6J, DBA/2J, BALB/cJ, and BXD5) and an F2 intercross between A/J and BXD5.
      Striatal volume ranged from 20 to 37 mm3. Neuron-packing density ranged from
      approximately 50,000 to 100,000 neurons/mm3, and the striatal neuron population
      ranged from 1.4 to 2.5 million. Inbred animals with larger brains had larger
      striata but lower neuron-packing density resulting in a narrow range of average
      neuron populations. In contrast, there was a strong positive correlation between
      volume and neuron number among intercross progeny. We mapped two quantitative
      trait loci (QTLs) with selective effects on striatal architecture. Bsc10a maps to
      the central region of Chr 10 (LRS of 17.5 near D10Mit186) and has intense effects
      on striatal volume and moderate effects on brain volume. Stnn19a maps to distal
      Chr 19 (LRS of 15 at D19Mit123) and is associated with differences of up to
      400,000 neurons among animals. CONCLUSION: We have discovered remarkable
      numerical and volumetric variation in the mouse striatum, and we have been able
      to map two QTLs that modulate independent anatomic parameters.

PMID- 11319942
TI  - Expression of nm23-H1 gene product in esophageal squamous cell carcinoma and its
      association with vessel invasion and survival.
AB  - BACKGROUND: We assessed the nm23-H1 gene product expression and its relationship
      with lymphatic and blood vessel invasion in patients with esophageal squamous
      cell carcinoma. METHODS: Formalin-fixed and paraffin-embedded tissue sections
      from 45 patients who were treated surgically were used in this study.
      Pathologists graded lymphatic and blood vessel invasion in each of the tissue
      samples. Expression of nm23-Hl gene product was determined using a specific
      monoclonal antibody. RESULTS: Expression of nm23-H1 gene product was present in
      17 (37.8%) cases. We found an inverse correlation between nm23-H1 gene product
      expression and lymphatic vessel invasion, whereas no correlation between nm23-H1
      gene product expression and blood vessel invasion. Overall survival rate was not
      different between nm23-H1 gene product positive and negative patients (p = 0.21).
      However, reduced expression of nm23-H1 gene product was associated with shorter
      overall survival in patients with involved lymph nodes (p < 0.05), but not in
      patients without involved lymph nodes (p = 0.87). CONCLUSIONS: In patients with
      esophageal squamous cell carcinoma, there appears to be an inverse relationship
      between nm23-H1 gene product expression and lymphatic vessel invasion.
      Furthermore, nm23-H1 gene product expression might be a prognostic marker in
      patients with involved lymph nodes. Our data does not demonstrate any correlation
      between nm23-H1 gene product expression and blood vessel invasion.

PMID- 11319943
TI  - Upregulation of the SERCA-type Ca2+ pump activity in response to endoplasmic
      reticulum stress in PC12 cells.
AB  - BACKGROUND: Ca2+-ATPases of endoplasmic reticulum (SERCAs) are responsible for
      maintenance of the micro- to millimolar Ca2+ ion concentrations within the
      endoplasmic reticulum (ER) of eukaryotic cells. This intralumenal Ca2+ storage is
      important for the generation of Ca2+ signals as well as for the correct folding
      and posttranslational processing of proteins entering ER after synthesis. ER
      perturbations such as depletion of Ca2+ or abolishing the oxidative potential,
      inhibition of glycosylation, or block of secretory pathway, activate the Unfolded
      Protein Response, consisting of an upregulation of a number of ER-resident
      chaperones/stress proteins in an effort to boost the impaired folding capacity.
      RESULTS: We show here that in PC12 cells, depletion of ER Ca2+ by EGTA, as well
      as inhibition of disulphide bridge formation within the ER by dithiotreitol or
      inhibition of N-glycosylation by tunicamycin, led to a 2- to 3-fold increase of
      the SERCA-mediated 45Ca2+ transport to microsomes isolated from cells exposed to
      these stress agents. The time course of this response corresponded to that for
      transcriptional upregulation of ER stress proteins, as well as to the increase in
      the SERCA2b mRNA, as we recently observed in an independent study. CONCLUSIONS:
      These findings provide the first functional evidence for the increase of SERCA
      pumping capacity in cells subjected to the ER stress. Since at least three
      different and unrelated mechanisms of eliciting the ER stress response were found
      to cause this functional upregulation of Ca2+ transport into the ER, these
      results support the existence of a coupling between the induction of the UPR
      pathway in general, and the regulation of expression of at least one of the SERCA
      pump isoforms.

PMID- 11319967
TI  - Abstracts from meeting 13 October 2000.

PMID- 11319968
TI  - Proceedings of Semon Club, 12 May 2000.

PMID- 11319944
TI  - Waiting lists for radiation therapy: a case study.
AB  - BACKGROUND: Why waiting lists arise and how to address them remains unclear, and
      an improved understanding of these waiting list "dynamics" could lead to better
      management. The purpose of this study is to understand how the current shortage
      in radiation therapy in Ontario developed; the implications of prolonged waits;
      who is held accountable for managing such delays; and short, intermediate, and
      long-term solutions. METHODS: A case study of the radiation therapy shortage in
      1998-99 at Princess Margaret Hospital, Toronto, Ontario, Canada. Relevant
      documents were collected; semi-structured, face-to-face interviews with ten
      administrators, health care workers, and patients were conducted, audio-taped and
      transcribed; and relevant meetings were observed. RESULTS: The radiation therapy
      shortage arose from a complex interplay of factors including: rising cancer
      incidence rates; broadening indications for radiation therapy; human resources
      management issues; government funding decisions; and responsiveness to previous
      planning recommendations. Implications of delays include poorer cancer control
      rates; patient suffering; and strained doctor-patient relationships. An
      incompatible relationship exists between moral responsibility, borne by
      government, and legal liability, borne by physicians. Short-term solutions
      include re-referral to centers with available resources; long-term solutions
      include training and recruiting health care workers, improving workload
      standards, increasing compensation, and making changes to the funding formula.
      CONCLUSION: Human resource planning plays a critical role in the causes and
      solutions of waiting lists. Waiting lists have harsh implications for patients.
      Accountability relationships require realignment.

PMID- 11319969
TI  - Sexually transmitted diseases: magnitude, determinants and consequences.
AB  - Sexually transmitted diseases (STDs) including human immuno-deficiency virus
      (HIV) infections constitute a major reproductive health burden for sexually
      active individuals. The short-term and long-term consequences of STD have been
      well documented and include genital and other cancers, pelvic inflammatory
      disease, ectopic pregnancy, infertility, and adverse outcomes of pregnancy
      including pre-term delivery and low birth weight. The burden of sexually
      transmitted infections falls disproportionately on the young, the poor,
      minorities and women. At the societal level, there is a continuing need to
      educate people, particularly adolescents, about their risk for STDs and their
      sequelae and to increase the use of barrier methods including condoms. Policy
      decisions that facilitate more open discussion of sexuality and STDs, and that
      expand the accessibility and acceptability of sexual risk assessment, STD
      screening and treatment services would help decrease STD rates in the United
      States to levels similar to those observed in other industrialized countries.

PMID- 11319970
TI  - The dysfunctional foreskin.
AB  - Although important, the foreskin is not absolutely essential to penile function.
      Dysfunction is common and a cause of considerable morbidity, and is sometimes
      associated with mortality from squamous cell carcinoma (SCC). Penile dermatoses
      herald, complicate or cause preputial dysfunction. Their effective diagnosis and
      management reduces morbidity and possibly mortality. Medical treatment has its
      limitations and circumcision is often required.

PMID- 11319971
TI  - Testicular atrophy in 80 HIV-positive patients: a multivariate statistical
      analysis.
AB  - This retrospective study of risk factors for testicular atrophy in HIV-infected
      men investigates the relationship between complications of AIDS such as wasting
      or opportunistic illness and testicular atrophy. Microscopic sections of the
      right testis were evaluated for testicular atrophy by assessing the mean score in
      each of 80 selected HIV-infected patients who underwent an autopsy during a one
      year period. A significant association was observed between testicular atrophy
      and body mass index (BMI) (P=0.0496). Thus, underweight patients with HIV
      infection were 3.52 times more likely to have testicular atrophy than those with
      acceptable body weight. Other significant associations between other variables
      were not found.

PMID- 11319972
TI  - HIV seroprevalence among military blood donors in Manica Province, Mozambique.
AB  - HIV seroprevalence data show an alarming HIV situation in central Mozambique, but
      little is known about the situation of HIV in Mozambican military personnel. This
      study is a retrospective analysis of laboratory records for voluntary blood
      donors at a rural hospital from January 1997 through December 1999. The hospital
      screened blood samples with HIV SPOT rapid test for HIV and rapid plasma reagin
      (RPR) serological test for syphilis. Of the 797 blood donors during this period,
      110 (13.8%) were military personnel of whom 39.1% were HIV positive (35.0% in
      1997, 33.3% in 1998 and 48.7% in 1999). Among the 687 nonmilitary donors 15.3%
      were HIV positive (P<0.0001 vs military). 74.4% of HIV-positive military
      personnel were also RPR positive. Conversely, only 3.0% of HIV-negative military
      donors were RPR positive. In light of the high rates of HIV and syphilis in
      military personnel, aggressive intervention measures must be taken to prevent and
      treat HIV and STDs in this population.

PMID- 11319973
TI  - The endogenous interferon system in anal squamous epithelial lesions with
      different grades from HIV-positive individuals.
AB  - Anal intraepithelial lesions (ASILs) are considered as precursors of anal cancer.
      The incidence of high-grade ASIL (HSIL) and progression of low-grade ASIL (LSIL)
      to HSIL are high in HIV-positive men. Endogenous cytokines, such as interferons
      (IFNs) play an important role in the regulation of proliferation and immune
      responses in epithelial cells, and thus, they might control the above-mentioned
      progression events. Accordingly, we determined mRNA levels of IFN-gamma and IFN
      gamma receptors, levels of IFN-gamma receptor-associated kinases (JAK1 and TYK2)
      and signalling molecules (signal transducer and activator of transcription-1
      [STAT1], STAT3, interferon-responsive-factor-1 [IRF-1] and IRF-2) as well as
      inhibitors of cytokine signalling (protein inhibitor of activated STAT1 [PIAS1]
      and suppressor of cytokine signalling 2 [SOCS2]) in biopsies of anal condylomas,
      LSILs as well as HSILs from HIV-positive individuals by a semi-quantitative
      reverse transcribed polymerase chain reaction (RT-PCR) method. We found that HSIL
      significantly differs in expression of these genes from LSIL and condylomas.
      Expression profile of HSIL samples showed activation of STAT3 signalling,
      probably accounting for the observed high levels of genes that support cellular
      proliferation (IRF-2, c-fos and c-myc). Decreases in levels of suppressors (IFN
      gamma and IRF-1) and JAK1 kinase, but increases in levels of inhibitors of
      cytokine signalling (PIAS1 and SOCS2) might also contribute to the altered
      cytokine signalling in HSIL biopsies. These findings might reveal important
      molecular events associated with progression of LSIL to HSIL in HIV-infected men.

PMID- 11319974
TI  - Effect of highly active antiretroviral therapy on cytomegalovirus antigenaemia in
      AIDS patients.
AB  - To assess the effect of highly active antiretroviral therapy (HAART) on
      cytomegalovirus (CMV) antigenaemia in AIDS patients, 70 patients with CD4+ cell
      counts < or = 50/mm3 and positive anti-(CMV) immunoglobulin G (IgG) were tested
      at 15-30 day intervals for CMV antigenaemia. We selected those patients who had
      been followed up for more than 3 months. Three patient profiles were defined: A,
      followed up before the introduction of HAART; B, followed up before and after the
      use of HAART; and C, followed up after the use of HAART. Thirty-nine patients
      were included, 12 in group A, 17 in group B, and 10 in group C. Group A patients
      presented a lower median CD4+ cell count compared with groups B and C patients
      (9, 122 and 127 cells/mm3, respectively), with the increase in the last 2 groups
      being related to the use of HAART (P<0.001). A lower proportion of positive
      antigenaemia was observed in group B after the introduction of HAART compared
      with the time before HAART (P=0.02). HAART caused an immunological improvement
      and was found to be associated with negativity of CMV antigenaemia.

PMID- 11319975
TI  - Prognostic score of short-term survival in HIV-infected patients admitted to
      medical intensive care units.
AB  - A retrospective cohort was set up to identify prognostic factors associated with
      in-hospital survival in HIV-infected patients admitted to medical intensive care
      units (MICUs), from 1991 to 1994. Survival from MICU admission to hospital
      discharge (or in-hospital fatal issue) was estimated and a prognostic score at
      MICU admission was developed. One hundred and thirty patients were recruited of
      whom 20% were AIDS-free prior to admission. In-hospital mortality rate was 65%.
      Median survival was 20 days. The following variables were predictive of
      mortality: Simplified Acute Physioloy Score II (SAPS II): (hazard ratio [HR]=1.5
      for 10 points higher, P<10(-3)), time between HIV diagnosis and admission >5
      years (HR=2.7, P<10(-4)), hypoalbuminaemia (HR=1.2 per 5 g/l lower, P=0.03). The
      prognostic score developed was: SAPS II+25 (if time between HIV diagnosis and
      MICU admission >5 years) albuminaemia (g/l). A new prognostic score including
      SAPS II, prior HIV history and albuminaemia better reflected the in-hospital
      mortality than SAPS II alone. Our findings may still be useful to better evaluate
      the immediate prognosis of current HIV-infected patients admitted to MICU,
      particularly those naive to antiretroviral therapy or in treatment failure.

PMID- 11319976
TI  - Gay men's estimates of the likelihood of HIV transmission in sexual behaviours.
AB  - In 3 studies we recorded gay men's estimates of the likelihood that HIV would be
      transmitted in various sexual behaviours. In Study 1 (data collected 1993, n=92),
      the men were found to believe that transmissibility is very much greater than it
      actually is; that insertive unprotected anal intercourse (UAI) by an HIV-infected
      partner is made safer by withdrawal before ejaculation, and very much safer by
      withdrawal before either ejaculation or pre-ejaculation; that UAI is very much
      safer when an infected partner is receptive rather than insertive; that insertive
      oral sex by an infected partner is much less risky than even the safest variant
      of UAI; that HIV is less transmissible very early after infection than later on;
      and that risk accumulates over repeated acts of UAI less than it actually does.
      In Study 2 (data collected 1997/8, n=200), it was found that younger and older
      uninfected men generally gave similar estimates of transmissibility, but that
      infected men gave somewhat lower estimates than uninfected men; and that
      estimates were unaffected by asking the men to imagine that they themselves,
      rather than a hypothetical other gay man, were engaging in the behaviours.
      Comparison of the 1993 and 1997/8 results suggested that there had been some
      effect of an educational campaign warning of the dangers of withdrawal; however,
      there had been no effect either of a campaign warning of the dangers of receptive
      UAI by an infected partner, or of publicity given to the greater transmissibility
      of HIV shortly after infection. In Study 3 (data collected 1999, n=59), men
      induced into a positive mood were found to give lower estimates of
      transmissibility than either men induced into a neutral mood or men induced into
      a negative mood. It is argued that the results reveal the important contribution
      made to gay men's transmissibility estimates by cognitive strategies (such as the
      'availability heuristic' and 'anchoring and adjustment') known to be general
      characteristics of human information-processing. Implications of the findings for
      AIDS education are discussed.

PMID- 11319977
TI  - Management of chronic prostatitis in Genitourinary Medicine clinics in the United
      Kingdom's North Thames Region 2000.
AB  - Twenty-two Genitourinary Medicine (GUM) clinics in North Thames participated in a
      survey of policies and case notes audit of chronic prostatitis managed within the
      past 2 years, compared with the UK National Guideline. For 32/33 cases notes
      reviewed (97%) chronic abacterial prostatitis/chronic pelvic pain syndrome
      (CAP/CPPS) were diagnosed. Of these, 14/32 cases (44%) were following non
      chlamydial non-gonococcal urethritis (NGU), 1/32 cases (3%) followed Chlamydia
      trachomatis infection and for 17/32 cases (53%) no predisposing cause was
      identified. The single case of chronic bacterial prostatitis (CBP) was caused by
      prostatic infection with Staphylococcus spp. All cases were prescribed
      antibiotics, initial follow-up appointments coinciding with completion of
      antibiotics. Fourteen cases (42%) were discharged following GUM clinic
      management; only 7 of these cases (50%) were asymptomatic, the others having
      residual problems. Nine cases (27%) were referred to a specialist. Ten cases
      (30%) defaulted follow-up appointments; 7 of these did not attend their first
      follow-up appointments.

PMID- 11319978
TI  - Audit of HIV testing: who, why and when?
AB  - The risk factors, referral pattern and presence/absence of genital tract symptoms
      and/or sexually transmitted infections (STIs) in 189 patients having HIV
      counselling and/or testing at genitourinary medicine (GUM) clinics are reviewed.
      Eighty per cent were concerned about heterosexual transmission, 9.5% men who have
      sex with men (MSM) and 4.8% intravenous drug users (IDUs). Heterosexuals and
      first-time GUM attenders were more likely to have sought prior advice from their
      general practitioner (GP). The majority were asymptomatic for genital tract
      infections, but 83% accepted an STI screen, with 44 STIs being diagnosed. Only
      one individual who had attended primarily for HIV screening was found to have an
      STI. About half of individuals presented within the window period, and of those
      stating that they wished to proceed with deferred testing, half subsequently
      failed to return, resulting in wasted health adviser appointments.

PMID- 11319979
TI  - Successful treatment of molluscum contagiosum with topical imiquimod in a
      severely immunocompromised HIV-positive patient.
AB  - Molluscum contagiosum is a common viral infection in the immuno-compromised HIV
      positive patient where it is often severe and affecting the face and neck. It is
      frequently resistant to conventional, locally destructive therapies. Anecdotal
      evidence suggests that the immunomodulatory drug imiquimod might be a valid
      therapeutic option in this group of patients. We report the case of a severely
      immunocompromised HIV-positive patient with resistant facial molluscum
      contagiosum lesions that responded to topical imiquimod. The response to therapy
      and the possible implications for pathogenesis are discussed.

PMID- 11319980
TI  - An aggressive neuroendocrine tumour in a man with AIDS.
AB  - Pancreatic neuroendocrine tumours (PETs), though rare, are usually slow growing
      tumours with a relatively good prognosis. We describe a case of an aggressive
      malignant neuroendocrine tumour of the pancreas occurring in an AIDS patient,
      which has not been reported previously.

PMID- 11319982
TI  - International Union against Sexually Transmitted Infections.

PMID- 11319984
TI  - The emerging AIDS crisis in Russia: review of enabling factors and prevention
      needs.

PMID- 11319985
TI  - HIV seroprevalence among military blood donors in Manica Province, Mozambique.

PMID- 11319986
TI  - The fascinating development of sexually transmitted diseases in the Asia-Pacific
      region.

PMID- 11319987
TI  - Young men's views about topical microbicides.

PMID- 11319989
TI  - General health status measures for people with cognitive impairment: learning
      disability and acquired brain injury.
AB  - BACKGROUND: Currently there is a wide range of health status measures that aim to
      assess general health status in people with cognitive impairment. However, the
      validity and/or applicability to this patient group are largely unknown. This has
      implications for the assessment of treatment outcomes and rehabilitation, for
      prognostic purposes, for planning services, and for determining the benefits and
      adverse effects of health technologies targeted at these patient groups.
      OBJECTIVES: (1) To identify the general health status measures that have been
      validated in patients with cognitive impairment. (2) To assess the extent to
      which these measures have been validated. (3) To draw out the implications of the
      findings for the use of existing measures and for future primary research in this
      area. METHODS. SELECTION CRITERIA: Studies that assessed general health status in
      people with cognitive impairment due to acquired brain injury (traumatic brain
      injury, cerebro-vascular accident or multiple sclerosis (MS)) or learning
      disability (LD) were included in the review. Studies that used general health
      status instruments measuring only one general health dimension, and studies that
      only featured participants with cognitive impairment due to dementia were
      excluded. METHODS. SEARCH STRATEGY: A wide range of relevant databases were
      searched for studies on cognitive impairment, general health status measures, and
      validation of health status measures. A handsearch of general health status
      bibliographies was also conducted. Data were collected on the general health
      status measure used, the population characteristics, aims of the study, validity
      details, and conclusions. RESULTS: The review includes data from 71 studies,
      reported in 83 separate publications. In total 34 different general health status
      measures were described in the 83 publications, with the Sickness Impact Profile
      (SIP) and the Short Form-36 (SF-36) the most frequently used measures (20 and 19
      studies, respectively). These studies included a total of 98 instrument
      validations, 52 of which definitely or probably included people with cognitive
      impairment. Six measures were extensively validated (quality scores ranged from
      0.25 to 0.5, on a scale from 0 to 1) in studies in which more than 50% of the
      respondents were people with cognitive impairment. A further three measures were
      also validated in studies in which more than 50% of the respondents were people
      with cognitive impairment, but their level of validation was more limited
      (quality scores ranged from 0.1 to 0.2). Five measures were validated in studies
      in which 20-50% of the respondents were cognitively impaired, which may limit
      their relevance to participants with cognitive impairment (quality scores ranged
      from 0.1 to 0.6). The SF-36 was also validated in two studies in which 20-50% of
      the respondents were cognitively impaired and the quality score was 0.3. Finally,
      nine of the measures were only validated in studies in which less than 20% of the
      respondents were cognitively impaired. For these measures it was unclear whether
      the findings applied to people with cognitive impairment. CONCLUSIONS: Very few
      measures have been validated specifically for cognitively impaired respondents.
      Studies where at least 50% of the respondents were cognitively impaired generally
      showed poorer validity results compared with studies with fewer cognitively
      impaired persons, indicating that general health status measures designed for the
      general population are not automatically suitable for people with cognitive
      impairment. The few measures that were specifically developed for people with
      cognitive impairment also reported poor validity results. Therefore, there are no
      validated instruments available for use in cognitively impaired respondents;
      existing measures, specifically designed for use in these populations, should be
      used with caution. The most promising measure is the MS-Quality of Life Interview
      (MS-QLI) for MS patients. The MS-QLI was thoroughly validated in 300 MS patients
      and the results were good, except for the 'social function' subscale. However,
      only 20-50% of the respondents in this study had cognitive impairment. Most
      information on the validity of general health status measures was found in
      studies among people with LD. For these patients, six measures were found that
      have been validated in a populations where more than 50% of the respondents were
      cognitively impaired LD patients. CONCLUSIONS: (1) Existing general health status
      measures should be used with caution in individuals with cognitive impairments.
      (2) There is no evidence to indicate the most suitable general health status
      measure for use in economic evaluations of cognitive impairment. (3) There is
      little evidence to support the validity of proxy assessments in cognitively
      impaired populations. (ABSTRACT TRUNCATED)

PMID- 11319990
TI  - Effects of educational and psychosocial interventions for adolescents with
      diabetes mellitus: a systematic review.
AB  - BACKGROUND: Insulin-dependent diabetes mellitus, also known as type 1 diabetes,
      is a life-threatening condition and is the third most common chronic illness
      among young people. As a result of minimal or non-existent insulin production,
      people with diabetes must take over the normally automatic task of regulation of
      blood glucose levels. This is achieved by a complex regimen involving multiple,
      daily administrations of insulin coordinated with dietary intake and energy
      expenditure and monitored by blood glucose testing. OBJECTIVES: To examine the
      effectiveness of educational and psychosocial interventions for adolescents with
      type 1 diabetes designed to improve their diabetes management. Specifically, it
      addressed the following research questions: (1) Do educational and psychosocial
      interventions for adolescents with type 1 diabetes have beneficial effects on
      biological and psychosocial outcomes? (2) Are there types or features of
      interventions that have been shown to be more effective than others? (3) What
      evidence is there of the cost-effectiveness of interventions? METHODS: A search
      strategy was formulated, piloted and refined. Three journals were handsearched,
      11 electronic databases were searched and personal contacts, flyers, conferences
      and websites were used to notify the research community of the review to access
      further literature. This process generated 10,535 abstracts, which, after
      screening, resulted in 367 articles identified for retrieval. This number was
      augmented by hand-searching, personal contact and exploding references, and a
      final total of 457 articles were scrutinised. Of these, 64 reports describing 62
      studies were identified as empirical papers evaluating educational or
      psychosocial interventions. The relevant data were extracted from the papers and
      summary tables for each study were prepared. Where possible, effect sizes were
      computed for outcomes from studies that included a randomised control group (CG)
      and other relevant information. RESULTS: A descriptive analysis of the 62 studies
      was undertaken. Most studies (67.7%) were conducted in the USA and 41% were
      randomised controlled trials (RCTs), none of which were UK-based. Only 48% of the
      reports provided an explicit theoretical rationale for the intervention. The mean
      number of participants was 53.8. The studies took place in various settings,
      evaluated a variety of interventions, involved various interventionists,
      addressed various components and assessed the effects by a range of outcomes,
      including measures of metabolic control and psychological and behavioural
      outcomes. Follow-up assessments were relatively rare. RESULTS - THE EFFECTIVENESS
      OF INTERVENTIONS: The 25 RCTs were examined in more detail and three of the most
      effective were described in depth. Effect sizes could be calculated for 14
      studies. The mean (pooled) effect size for psychosocial outcomes was 0.37 and
      0.33 for glycated haemoglobin with outliers (0.08 without outliers), indicating
      that these interventions have small to medium beneficial effects on diabetes
      management outcomes. A narrative review of the 21 pre-post studies with no CG was
      performed, including evaluations of interventions conducted at summer camps,
      interventions for poorly controlled patients and educational interventions. All
      studies reported beneficial effects. RESULTS - COST-EFFECTIVENESS: Few studies
      addressed economic considerations associated with interventions, and the lack of
      information on costs and the diversity of outcomes included by investigators
      impeded cost- effectiveness comparisons. Shorter hospitalisation at diagnosis is
      at least as effective in achieving control and avoiding complications in
      adolescence as longer stays. Home care may result in improved outcomes but may
      not be cheaper than hospital care at diagnosis. Targeting poorly controlled
      subjects may reduce adverse events and hospitalisations and may be more cost
      effective than generic interventions. There is a need for rigorous cost
      effectiveness studies of educational and psychosocial interventions for
      adolescents with type 1 diabetes that include longer-term considerations.
      CONCLUSIONS: The following conclusions were drawn from this review: (1)
      Educational and psychosocial interventions have small to medium beneficial
      effects on various diabetes management outcomes. (2) Well-designed trials of such
      interventions are needed in the UK (no completed RCTs of educational or
      psychosocial interventions for adolescents with type 1 diabetes conducted in the
      UK were found). (3) The evidence, arising primarily from studies in the USA,
      provides a starting point for the design of interventions in the UK. (4)
      Quantitative and narrative analysis of the evidence suggested that interventions
      are more likely to be effective if they demonstrate the inter-relatedness of the
      various aspects of diabetes management. (ABSTRACT TRUNCATED)

PMID- 11319991
TI  - Statistical assessment of the learning curves of health technologies.
AB  - OBJECTIVES: (1) To describe systematically studies that directly assessed the
      learning curve effect of health technologies. (2) Systematically to identify
      'novel' statistical techniques applied to learning curve data in other fields,
      such as psychology and manufacturing. (3) To test these statistical techniques in
      data sets from studies of varying designs to assess health technologies in which
      learning curve effects are known to exist. METHODS - STUDY SELECTION (HEALTH
      TECHNOLOGY ASSESSMENT LITERATURE REVIEW): For a study to be included, it had to
      include a formal analysis of the learning curve of a health technology using a
      graphical, tabular or statistical technique. METHODS - STUDY SELECTION (NON
      HEALTH TECHNOLOGY ASSESSMENT LITERATURE SEARCH): For a study to be included, it
      had to include a formal assessment of a learning curve using a statistical
      technique that had not been identified in the previous search. METHODS - DATA
      SOURCES: Six clinical and 16 non-clinical biomedical databases were searched. A
      limited amount of handsearching and scanning of reference lists was also
      undertaken. METHODS - DATA EXTRACTION (HEALTH TECHNOLOGY ASSESSMENT LITERATURE
      REVIEW): A number of study characteristics were abstracted from the papers such
      as study design, study size, number of operators and the statistical method used.
      METHODS - DATA EXTRACTION (NON-HEALTH TECHNOLOGY ASSESSMENT LITERATURE SEARCH):
      The new statistical techniques identified were categorised into four subgroups of
      increasing complexity: exploratory data analysis; simple series data analysis;
      complex data structure analysis, generic techniques. METHODS - TESTING OF
      STATISTICAL METHODS: Some of the statistical methods identified in the systematic
      searches for single (simple) operator series data and for multiple (complex)
      operator series data were illustrated and explored using three data sets. The
      first was a case series of 190 consecutive laparoscopic fundoplication procedures
      performed by a single surgeon; the second was a case series of consecutive
      laparoscopic cholecystectomy procedures performed by ten surgeons; the third was
      randomised trial data derived from the laparoscopic procedure arm of a
      multicentre trial of groin hernia repair, supplemented by data from non
      randomised operations performed during the trial. RESULTS - HEALTH TECHNOLOGY
      ASSESSMENT LITERATURE REVIEW: Of 4571 abstracts identified, 272 (6%) were later
      included in the study after review of the full paper. Some 51% of studies
      assessed a surgical minimal access technique and 95% were case series. The
      statistical method used most often (60%) was splitting the data into consecutive
      parts (such as halves or thirds), with only 14% attempting a more formal
      statistical analysis. The reporting of the studies was poor, with 31% giving no
      details of data collection methods. RESULTS - NON-HEALTH TECHNOLOGY ASSESSMENT
      LITERATURE SEARCH: Of 9431 abstracts assessed, 115 (1%) were deemed appropriate
      for further investigation and, of these, 18 were included in the study. All of
      the methods for complex data sets were identified in the non-clinical literature.
      These were discriminant analysis, two-stage estimation of learning rates,
      generalised estimating equations, multilevel models, latent curve models, time
      series models and stochastic parameter models. In addition, eight new shapes of
      learning curves were identified. RESULTS - TESTING OF STATISTICAL METHODS: No one
      particular shape of learning curve performed significantly better than another.
      The performance of 'operation time' as a proxy for learning differed between the
      three procedures. Multilevel modelling using the laparoscopic cholecystectomy
      data demonstrated and measured surgeon-specific and confounding effects. The
      inclusion of non-randomised cases, despite the possible limitations of the
      method, enhanced the interpretation of learning effects. CONCLUSIONS - HEALTH
      TECHNOLOGY ASSESSMENT LITERATURE REVIEW: The statistical methods used for
      assessing learning effects in health technology assessment have been crude and
      the reporting of studies poor. CONCLUSIONS - NON-HEALTH TECHNOLOGY ASSESSMENT
      LITERATURE SEARCH: A number of statistical methods for assessing learning effects
      were identified that had not hitherto been used in health technology assessment.
      There was a hierarchy of methods for the identification and measurement of
      learning, and the more sophisticated methods for both have had little if any use
      in health technology assessment. This demonstrated the value of considering
      fields outside clinical research when addressing methodological issues in health
      technology assessment. CONCLUSIONS - TESTING OF STATISTICAL METHODS: It has been
      demonstrated that the portfolio of techniques identified can enhance
      investigations of learning curve effects. (ABSTRACT TRUNCATED)

PMID- 11319992
TI  - Uveal melanoma: implications of tumor doubling time.

PMID- 11319995
TI  - Acromegaly and junctional visual field loss.

PMID- 11319996
TI  - Intracameral lidocaine for phacoemulsification.

PMID- 11319999
TI  - Corneal ectasia after refractive surgery.

PMID- 11320000
TI  - Acute comitant esotropia in Chiari 1 malformation.

PMID- 11320001
TI  - Trabeculectomy with mitomycin-C in pediatric glaucomas.

PMID- 11320003
TI  - Trabeculectomy with mitomycin-C in pediatric glaucomas.

PMID- 11320007
TI  - Acanthoamoeba attachment to contact lenses.

PMID- 11320009
TI  - Inhaled corticosteroids and glaucoma.

PMID- 11320010
TI  - Retina and vitreous pathology after laser-assisted in situ keratomileusis: is
      there a cause-effect relationship?

PMID- 11320011
TI  - Photodynamic therapy of subfoveal choroidal neovascularization in pathologic
      myopia with verteporfin. 1-year results of a randomized clinical trial--VIP
      report no. 1.
AB  - OBJECTIVE: To determine if photodynamic therapy with verteporfin (Visudyne; CIBA
      Vision Corp, Duluth, GA) can improve the chance of stabilizing or improving
      vision (<8 letter loss) safely in patients with subfoveal choroidal
      neovascularization (CNV) caused by pathologic myopia. DESIGN: Multicenter, double
      masked, placebo-controlled, randomized clinical trial at 28 ophthalmology
      practices in Europe and North AMERICA: PARTICIPANTS: One hundred twenty patients
      with subfoveal CNV caused by pathologic myopia with a greatest linear dimension
      no more than 5400 microM and best-corrected visual acuity (Snellen equivalent) of
      approximately 20/100 or better. INTERVENTION: Patients were randomly assigned
      (2:1) to verteporfin (6 mg per square meter of body surface area; n = 81) or
      placebo (5% dextrose in water; n = 39) administered via intravenous infusion of
      30 ml over 10 minutes. Fifteen minutes after the start of the infusion, a laser
      light at 689 nm was delivered at an intensity of 600 mW/cm(2) over 83 seconds to
      give a light dose of 50 J/cm(2) to a round spot size on the retina with a
      diameter of 1000, microM larger than the greatest linear dimension of the
      choroidal neovascular lesion. At follow-up examinations every 3 months,
      retreatment with either verteporfin or placebo (as assigned at baseline) was
      applied to areas of fluorescein leakage if present. MAIN OUTCOME MEASURES: The
      primary outcome was the proportion of eyes at the follow-up examination 12 months
      after study entry with fewer than eight letters (approximately 1.5 lines) of
      visual acuity lost, adhering to an intent-to-treat analysis. RESULTS: At
      baseline, more than 90% of each group had evidence of classic CNV (regardless of
      whether occult CNV was present) and only 12 (15%) and 5 (13%) cases in the
      verteporfin and placebo groups, respectively, had occult CNV (regardless of
      whether classic CNV was present). Seventy-nine of the 81 verteporfin-treated
      patients (98%) compared with 36 of the 39 placebo-treated patients (92%)
      completed the month 12 examination. Visual acuity, contrast sensitivity, and
      fluorescein angiographic outcomes were better in the verteporfin-treated eyes
      than in the placebo-treated eyes at every follow-up examination through the month
      12 examination. At the month 12 examination, 58 (72%) of the verteporfin-treated
      patients compared with 17 (44%) of the placebo-treated patients lost fewer than
      eight letters (P < 0.01), including 26 (32%) versus 6 (15%) improving at least
      five letters (>/=1 line). Seventy (86%) of the verteporfin-treated patients
      compared with 26 (67%) of the placebo-treated patients lost fewer than 15 letters
      (P = 0.01). Few ocular or other systemic adverse events were associated with
      verteporfin therapy compared with placebo treatment. CONCLUSIONS: Because
      photodynamic therapy with verteporfin can safely increase the chance of
      stabilizing or improving vision in patients with subfoveal CNV from pathologic
      myopia compared with a placebo, we recommend ophthalmologists consider
      verteporfin therapy for treatment of such patients.

PMID- 11320012
TI  - Traumatic macular hole: observations, pathogenesis, and results of vitrectomy
      surgery.
AB  - PURPOSE: To review our experience with vitrectomy surgery techniques for the
      treatment of traumatic macular holes and the biomicroscopic and surgical
      findings. DESIGN: Retrospective noncomparative, multicenter, case series.
      PARTICIPANTS AND INTERVENTION: Twenty-five patients with traumatic macular hole
      underwent surgical repair. INTERVENTION: Vitrectomy with membrane peeling and gas
      injection followed by prone positioning for 7 to 14 days. MAIN OUTCOME MEASURES:
      Postoperative evaluation included visual acuity testing, closure of the macular
      hole, and ocular complications. RESULTS: The macular hole was successfully closed
      in 24 of 25 cases (96%). The visual acuity improved two or more lines in 21 (84%)
      cases, and 16 (64%) achieved 20/50 or better vision. CONCLUSIONS: Vitrectomy
      surgery can successfully close macular holes associated with trauma and improve
      vision.

PMID- 11320013
TI  - Interferon-induced retinopathy in asymptomatic cancer patients.
AB  - OBJECTIVES: Interferon-induced ocular complications, including retinal ischemia
      and ischemic optic neuropathy, can be associated with significant visual loss. We
      report three cases of asymptomatic ischemic retinopathy in cancer patients
      receiving interferon. DESIGN: Retrospective, interventional, noncomparative small
      case series. METHODS: Retrospective review of the medical records and fundus
      photographs. RESULTS: Interferon-induced ischemic retinopathy can occur in
      asymptomatic cancer patients. The retinal changes are usually reversible with
      discontinuation of interferon therapy. CONCLUSIONS: These three cases underscore
      the importance of dilated funduscopic examination at baseline and during follow
      up, at least every 3 months, for all cancer patients receiving interferon to
      identify retinal toxicity at its earliest stages. A prospective study evaluating
      the incidence and severity of interferon retinopathy in cancer patients would be
      prudent.

PMID- 11320014
TI  - Acute multifocal placoid pigment epitheliopathy and central nervous system
      involvement: nine new cases and a review of the literature.
AB  - OBJECTIVE: The authors describe nine new cases of acute multifocal placoid
      pigment epitheliopathy (AMPPE) with associated central nervous system (CNS)
      involvement and permanent visual sequelae. The study includes a review of the
      literature and discussion of evaluation, management, and treatment options.
      DESIGN: Retrospective, noncomparative case series. PARTICIPANTS: Nine patients
      were identified with AMPPE and CNS involvement in addition to 22 patients
      reviewed in the literature. MAIN OUTCOME MEASURES: A review of nine patients with
      AMPPE and CNS involvement was performed. Charts were reviewed for age, gender,
      preceding viral prodromes, visual acuity, ophthalmologic examination findings,
      CNS findings, and treatment. RESULTS: Thirty-one patients (nine new patients)
      were diagnosed with AMPPE and various degrees of CNS involvement. Ages ranged
      from 8 to 54 years, with an average of 27 years. Twenty-one males (68%) and 10
      females (32%) were identified. Eleven patients (35%) had antecedent viral
      illnesses. Visual acuity was variable and ranged from 20/20 to count fingers. The
      spectrum of CNS findings ranged from headaches to sagittal sinus thrombosis.
      CONCLUSIONS: Acute multifocal placoid pigment epitheliopathy can be associated
      with CNS abnormalities and permanent visual deficits. Neuroimaging, lumbar
      puncture, and cerebral angiography analysis provide useful diagnostic tools when
      CNS involvement is suspected. Intravenous corticosteroids and collaboration with
      neurovascular colleagues should be considered in these situations. In cases
      complicated by CNS arteritis, immunosuppressive agents can be a beneficial
      adjunct to corticosteroids.

PMID- 11320015
TI  - Herpes simplex virus type 2 as a cause of acute retinal necrosis syndrome in
      young patients.
AB  - PURPOSE: To determine the causative virus in acute retinal necrosis (ARN)
      syndrome in a series of patients by calculation of modified Witmer coefficients.
      DESIGN: Noncomparative case series. PARTICIPANTS: Ten patients with ARN syndrome
      from four medical centers. METHODS: Aqueous samples, vitreous samples, or both
      were collected prospectively during surgery from patients with a clinical
      diagnosis of ARN syndrome. Serologic measures of intraocular and serum antibodies
      to potentially causative viruses were measured by enzyme-linked immunosorbent
      assay. MAIN OUTCOME MEASURES: Modified Witmer coefficients (immunoglobulin G and
      immunoglobulin A) for herpes simplex virus types 1 (HSV-1) and 2 (HSV-2),
      varicella zoster virus (VZV), and cytomegalovirus (CMV), as well as adenovirus
      type 2, were calculated from aqueous or vitreous samples, or both. RESULTS:
      Intraocular antibody measurements were strongly suggestive of a single diagnosis
      in 9 of 10 patients tested. Modified Witmer coefficients demonstrated intraocular
      antibody production to HSV in five patients and antibodies to VZV in four
      patients, and the measurement was inconclusive in one patient. No patients were
      positive for adenovirus or CMV. Strain-specific antibody titers demonstrated that
      all HSV-positive patients were reactive only to HSV-2. Herpes simplex virus type
      2 was found predominantly in younger patients with ARN syndrome (mean age, 21.2
      +/- 10 years; range, 17-39 years), whereas VZV was more commonly seen in older
      patients (mean age, 40.8 +/- 12.2 years; range, 29-58 years; P = 0.033).
      Immunoglobulin A testing confirmed immunoglobulin G testing in all patients
      examined. CONCLUSIONS: Although VZV is thought to be the most common cause of ARN
      syndrome, HSV-2 is an important cause of ARN syndrome, particularly in younger
      patients. Because infection with HSV-2 has important medical ramifications, these
      results suggest that determination of a causal agent should be considered in some
      cases of ARN syndrome.

PMID- 11320016
TI  - Subjective visual halos after sildenafil (Viagra) administration:
      Electroretinographic evaluation.
AB  - PURPOSE: The ophthalmologic and electroretinographic (ERG) findings in one
      subject with subjective visual disturbances after sildenafil administration are
      described. DESIGN: Interventional case report. METHODS: A complete ophthalmologic
      examination was performed, including best-corrected visual acuity and ERG,
      repeated 1 and 2 hours after administration of 100 mg of sildenafil. MAIN OUTCOME
      MEASURES: Rod responses were obtained over a range of retinal illuminances from
      those producing a minimum detectable response to those producing rod saturation.
      Intensity amplitude function was determined. RESULTS: At 2 hours after 100 mg of
      oral sildenafil, we observed significant variations from baseline in parameters
      of best-fit Naka-Rushton function; V(max) was notably higher, and K was 0.14 log
      units lower than baseline. CONCLUSIONS: Sildenafil administration resulted in a
      higher rod response to light stimuli and in a higher rod sensitivity. These
      findings are consistent with the weak PDE-6 inhibition induced by sildenafil.

PMID- 11320017
TI  - Estimated incidence of open-angle glaucoma in Olmsted County, Minnesota.
AB  - PURPOSE: To determine the incidence rates of open-angle glaucoma (OAG) in Olmsted
      County, MINNESOTA: DESIGN: Retrospective population-based estimate of incidence.
      PARTICIPANTS: From the medical histories of 60,666 residents of Olmsted County,
      Minnesota, who had ocular diagnoses during the study period, 114 subjects with
      newly diagnosed OAG were identified. METHODS: The database of the Rochester
      Epidemiology Project was used to identify all Olmsted County residents with a
      coded diagnosis of OAG, glaucoma suspect, or ocular hypertension during the
      period 1965 to 1980. Subjects newly diagnosed with and treated for OAG who also
      had documented clinical evidence of elevated intraocular pressure, optic nerve
      damage, and/or visual field loss consistent with glaucoma were included as
      incident cases. Population data for Olmsted County were drawn from United States
      Census data. Crude incidence data were adjusted to the age and gender
      distribution of the 1990 United States white population. MAIN OUTCOME MEASURES:
      Estimated incidence rates of OAG. RESULTS: The overall age- and gender-adjusted
      annual incidence rate of OAG in a predominantly Caucasian population is
      conservatively estimated to be 14.5 per 100,000 population. The rates increased
      with age from 1.6 in the fourth decade of life to 94.3 in the eighth decade.
      There was no significant difference in incidence by gender. The average annual
      rate of OAG in the last 2 years of the study was 27.7 compared with 12.3 before
      1979. This difference is suggestive of the effect of the introduction of a new
      medical therapy (timolol) for OAG during the last 2 years. CONCLUSIONS: The
      incidence rates of OAG increase markedly with advancing age, and screening
      efforts should be targeted at both men and women in the older age groups. The
      advent of new diagnostic and therapeutic modalities can have an effect on
      incidence rates.

PMID- 11320020
TI  - The sensitivity and specificity of scanning laser polarimetry in the detection of
      glaucoma in a clinical setting.
AB  - OBJECTIVE: A study was conducted to determine the sensitivity and specificity of
      masked experts in classifying results obtained from normal eyes, glaucomatous
      eyes, and eyes suspicious for glaucoma using the Nerve Fiber Analyzer GDx (Laser
      Diagnostic Technologies, San Diego, CA), a scanning polarimeter. DESIGN:
      Retrospective consecutive case series. METHODS: Consecutive subjects seen in a
      glaucoma clinic were imaged with the GDX: The masked printouts were distributed
      to nine experienced users of the machine, who were asked to classify the scan
      from each eye as normal, suspicious for glaucoma, or consistent with glaucoma. No
      specific guidelines for interpretation were used. The interpretations were
      compared with the known diagnoses obtained from review of the subjects' medical
      records. The number of correct diagnoses, false-positive answers (specificity),
      and false-negative answers (sensitivity) were noted for each observer and
      averaged for all nine. Interobserver agreement was calculated by use of the kappa
      statistic. MAIN OUTCOME MEASURES: False-positive and false-negative responses
      from reviewers' assessments compared with known diagnoses from chart review.
      RESULTS: A total of 104 eyes was included: 29 normal eyes, 33 eyes from glaucoma
      suspects, and 42 eyes with glaucoma. Interobserver agreement was moderate for
      normals (kappa = 0.42, P = 0.00) and glaucoma (kappa = 0.48, P = 0.00), but
      slight for glaucoma suspects (kappa = 0.09, P = 0.00). Overall, the average
      sensitivity was 74% and the specificity was 74%. If only considering whether or
      not the scan represented glaucoma (i.e., reviewer assessment of "suspect" meant
      "not glaucoma"), the average sensitivity was 86% and the specificity 83%. If only
      considering whether a scan was normal or not (i.e., reviewer assessment of
      "suspect" meant "abnormal"), the sensitivity was 83% and the specificity 86%.
      Eliminating glaucoma suspects (but allowing the assessment of "suspect")
      increased overall sensitivity to 80% and specificity to 79%. With suspects
      eliminated, sensitivity was 80% and specificity 91% for determination of
      glaucoma, and sensitivity was 93% and specificity 79% for determination of
      abnormality. CONCLUSIONS: Scanning laser polarimetry may have good sensitivity
      and specificity for separating normal from abnormal eyes, but it is not as good
      for classifying unknown subjects when glaucoma suspects are included. Evaluation
      of new parameters and continued clinical experience may help develop guidelines
      for interpretation and/or specific indicators for glaucomatous damage to increase
      the sensitivity and specificity.

PMID- 11320018
TI  - Quality of life in newly diagnosed glaucoma patients : The Collaborative Initial
      Glaucoma Treatment Study.
AB  - OBJECTIVE: The Collaborative Initial Glaucoma Treatment Study (CIGTS) was
      designed to determine whether patients with newly diagnosed open-angle glaucoma
      are better treated initially by medicine or immediate filtering surgery. This
      paper describes the quality-of-life (QOL) measurement approach, instruments
      included, and the CIGTS participants' QOL findings at the time of diagnosis.
      DESIGN: Baseline results from a randomized, controlled clinical trial.
      PARTICIPANTS: Six hundred seven patients from 14 clinical centers were enrolled.
      INTERVENTION: Patients randomized to initial medication received a stepped
      medical regimen (n = 307). Those randomized to initial surgery underwent a
      trabeculectomy (n = 300). The baseline interview was conducted before treatment
      initiation. All baseline and posttreatment QOL assessments were conducted by
      telephone from a centralized interviewing center. MAIN OUTCOME MEASURES: The
      primary outcome measure described in this paper was QOL. The QOL instrument is
      multidimensional and incorporates both disease-specific and generic measures,
      including the Visual Activities Questionnaire, Sickness Impact Profile, and a
      Symptom and Health Problem CHECKLIST: RESULTS: The correlations between QOL
      measures and clinical outcomes were in the expected direction, but relatively
      weak. At initial diagnosis, difficulty with bright lights and with light and dark
      adaptation were the most frequently reported symptoms related to visual function,
      whereas visual distortion was the most bothersome. Approximately half of the
      patients reported at least some worry or concern about the possibility of
      blindness. Within the Visual Activities Questionnaire, higher scores on the
      Peripheral Vision subscale were associated with more field loss (P < 0.01). In
      regression analyses controlling for sociodemographics and nonocular
      comorbidities, increased visual field loss was significantly associated with
      higher dysfunction among five disease-specific QOL measures (P < 0.05).
      CONCLUSIONS: Newly diagnosed glaucoma patients reported experiencing some visual
      function symptoms at the time of diagnosis that would not be intuitively expected
      based on clinical testing. Some discussion about the association between clinical
      presentation and worry about blindness may reduce unnecessary concern. These
      results provide the basis for long-term comparisons of the QOL effects of initial
      medical and surgical treatment for open-angle glaucoma.

PMID- 11320021
TI  - Correlation between optical coherence tomography, pattern electroretinogram, and
      visual evoked potentials in open-angle glaucoma patients.
AB  - OBJECTIVE: [corrected] To correlate the nerve fiber layer (NFL) thickness and the
      visual function evaluated by electrophysiologic retinal and cortical responses
      assessed in open-angle glaucoma (OAG) eyes. DESIGN: Prospective case-control
      study. PARTICIPANTS: Thirty glaucoma patients (mean age, 47.1 +/- 7.15 years;
      refractive error range, +/- 2 spherical equivalent) with a mean deviation of
      computerized static perimetry (24/2 Humphrey, Dublin, CA) from -5 to -28 dB and
      intraocular pressure less than 21 mmHg on pharmacologic treatment and 14 age
      matched control participants. METHODS: Nerve fiber layer thickness was measured
      by optical coherence tomography. Retinal and visual pathway function was assessed
      by simultaneously recording pattern electroretinograms (PERGs) and visual evoked
      potentials (VEPs) using high-contrast (80%) checkerboard stimuli (the single
      check edges subtend 15 minutes of the visual arc) reversed at the rate of two
      reversals per second. Linear regression analyses were adopted to establish the
      correlation between NFL thickness and PERG and VEP parameters. MAIN OUTCOME
      MEASURES: Nerve fiber layer thickness measurements in each quadrant (superior,
      inferior, nasal, and temporal) were taken and then averaged (12 values averaged)
      and identified as NFL overall, whereas the data obtained in the temporal quadrant
      only (three values averaged) were identified as NFL temporal. PERG P50 implicit
      time and P50-N95 amplitude and VEP P100 implicit time and N75-P100 amplitude were
      also measured. RESULTS: In OAG eyes, we found a significant (P < 0.01) reduction
      in NFL thickness in both NFL overall and NFL temporal evaluations with respect to
      the values observed in control eyes. PERG and VEP parameters showed a significant
      (P < 0.01) delay in implicit time and a reduction in peak-to-peak amplitude. In
      OAG eyes, the NFL overall and NFL temporal values were significantly correlated
      (P < 0.01) with the PERG P50 implicit time and P50-95 peak-to-peak amplitude. No
      correlations (P > 0.01) between NFL values and VEP parameters were found.
      CONCLUSIONS: There is a correlation between PERG changes and NFL thickness, but
      there is no correlation between VEP changes and NFL thickness in patients
      affected by OAG.

PMID- 11320022
TI  - Is Posner Schlossman syndrome benign?
AB  - PURPOSE: To determine the clinical course of patients with Posner Schlossman
      syndrome (PSS). DESIGN: Retrospective noncomparative case series. PARTICIPANTS:
      Fifty-three eyes of 50 patients. METHODS: The case notes of all patients with PSS
      seen at the Uveitis Clinic of Singapore National Eye Centre were reviewed for
      evidence of glaucoma damage and risk factors. MAIN OUTCOME MEASURES: Visual field
      and optic disc changes consistent with glaucoma. RESULTS: There were 28 men and
      22 women, and their mean age at onset was 35 years. Fourteen eyes (26.4%) were
      diagnosed to have developed glaucoma as a result of repeated attacks of PSS.
      Patients with 10 years or more of PSS have a 2.8 times higher risk (95%
      confidence interval 1.19-6.52) of developing glaucoma compared with patients with
      less than 10 years duration of the disease. Nine eyes (17%) underwent glaucoma
      filtering surgery with antimetabolites. Their postoperative follow-up ranged from
      15 to 50 months (mean, 37 months). Four eyes continued to have episodes of iritis
      after surgery, and one of these eyes had elevated intraocular pressure during the
      event. CONCLUSIONS: A significant number of patients with PSS have glaucoma
      develop over time, and they need to have their optic disc appearance and visual
      fields carefully monitored.

PMID- 11320023
TI  - Transscleral suture fixation of posterior chamber lenses combined with
      trabeculectomy.
AB  - OBJECTIVE: To evaluate the outcome of transscleral suture-fixated posterior
      chamber intraocular lens (PCIOL) implantation in glaucoma patients when combined
      with a trabeculectomy. DESIGN: A retrospective study of 56 consecutive glaucoma
      patients with a minimum follow-up of 6 months after transscleral suture-fixated
      PCIOL implantation combined with trabeculectomy. SETTING: Patients were drawn
      from the clinical glaucoma practice of the Kresge Eye Institute, Detroit,
      MICHIGAN: PATIENTS: Fifty-six eyes of 56 consecutive chronic glaucoma patients
      who had undergone transscleral suture-fixated PCIOL implantation in combination
      with a trabeculectomy were included in the analysis. RESULTS: The mean follow-up
      time was 38.5 +/- 19.1 months. Mean intraocular pressure (IOP) was significantly
      reduced, from 22.9 +/- 10.9 mmHg before surgery to 16.7 +/- 6.7 mmHg at the last
      follow-up visit (P = 0.0005), with the mean number of medications used also
      significantly decreased, from 2.3 +/- 0.9 to 1.9 +/- 0.9 (P = 0.0002).
      Postoperative IOP control to 21 mmHg or less was achieved or maintained in 84% of
      patients. Visual acuity improved or remained stable within two Snellen lines of
      the preoperative level in 39 eyes (70%) and within three Snellen lines in 45 eyes
      (80%) at the last follow-up visit. Overall, 46% to 68% of the patients had both
      stable visual acuity and satisfactory pressure control at the last postoperative
      visit, depending on criteria of varying stringency. However, 19 eyes (34%)
      required one or more additional surgical interventions for pressure control.
      Patients with anterior chamber intraocular lens (ACIOL) complications, diabetes
      mellitus, or a preoperative IOP level of more than 21 mmHg on maximum tolerated
      medications were especially prone to requiring additional surgical interventions.
      CONCLUSIONS: We conclude that transscleral suture-fixated PCIOL implantation can
      be combined successfully with a trabeculectomy and can be useful in glaucoma
      patients in need of both visual rehabilitation and IOP control. However, patients
      with ACIOL complications, diabetes, or preoperative IOP of more than 21 mmHg on
      maximum tolerated medications were prone to requiring additional surgical
      interventions.

PMID- 11320024
TI  - The early complications of cataract surgery: is routine review of patients 1 week
      after cataract extraction necessary?
AB  - OBJECTIVE: This study sought to define the nature and frequency of complications
      present 1 week after cataract surgery, to determine whether these complications
      are predictable, and to ascertain if patients undergoing cataract surgery require
      routine review at this time. DESIGN: Retrospective, noncomparative case series.
      PARTICIPANTS: One thousand consecutive patients undergoing cataract removal by
      either phacoemulsification or extracapsular extraction at a large teaching
      hospital between January 1996 and May 1998. Patients with both complicated and
      uncomplicated histories and surgeries were included. MAIN OUTCOME MEASURES:
      Nature and frequency of complications present 1 week after cataract surgery.
      RESULTS: At the routine 1-week visit, postoperative complications were observed
      in 41 of 1000 patients (4.1%). Twenty-one (51%) of these patients had a
      completely unremarkable history to that point, and whereas only four (19%) were
      symptomatic, 20 (95%) required a change to their postoperative management. The
      most significant unexpected complications were uveitis (seven cases), cystoid
      macular edema (four cases), and vitreous to the wound, exposed knots, and loose
      suture (one case of each). Complications were present in 20 of 257 (7.8%)
      patients with a preoperative or surgical risk factor, and there was a significant
      relationship between preoperative (P = 0.02), and combined preoperative and
      intraoperative risk factors (P = 0.001), and complications present at the 1-week
      review. The relationship between surgical risk factors and 1-week complications
      was not significant (P = 0.07). There were coexistent pathologic features in 19%
      of all eyes. Registrars performed 38% of surgeries, and 96% of cataracts were
      removed by phacoemulsification. Operative complications occurred in 6.7% of
      patients, most commonly a posterior capsule tear (4.4% of all cases).
      Complications were observed in 10% of eyes on the first postoperative day. Raised
      intraocular pressure was the complication in 88% of these patients. CONCLUSIONS:
      This study provides an overview of modern cataract surgery in a large teaching
      hospital and indicates that abandonment of routine 1-week review may result in
      the failure to detect significant postoperative complications.

PMID- 11320025
TI  - Keratitis, ulceration, and perforation associated with topical nonsteroidal anti
      inflammatory drugs.
AB  - PURPOSE: To report corneal complications associated with topical nonsteroidal
      anti-inflammatory drugs (NSAIDs). DESIGN: Retrospective, noncomparative
      interventional case series. PARTICIPANTS: Eighteen eyes of 16 patients with
      adverse corneal events associated with NSAID use. METHODS: Evaluation of 16
      patients referred for management of corneal complications during use of topical
      NSAIDs (ketorolac tromethamine [Acular], diclofenac sodium [Voltaren], diclofenac
      sodium [Falcon DSOS]). MAIN OUTCOME MEASURES: Type and severity of corneal
      complications. RESULTS: Of the 16 patients, two experienced severe keratopathy,
      three experienced ulceration, six experienced corneal or scleral melts, and five
      experienced perforations. Eleven patients had recent cataract surgery; nine of
      these were on concurrent topical steroids and antibiotics. Another patient who
      did not have recent surgery was using concurrent topical steroids without
      antibiotics for sarcoid uveitis. Systemic associations included two patients with
      rheumatoid arthritis, one patient with asymptomatic Sjogren's syndrome, and two
      with rosacea. CONCLUSIONS: Topical NSAIDs were associated with corneal
      complications in 18 eyes of 16 patients. Potential risk factors include
      conditions that predispose the patient to corneal melting, concurrent topical
      steroids, and epithelial keratopathy in the early postoperative period.

PMID- 11320026
TI  - Adjustable refractive surgery: 6-mm Artisan lens plus laser in situ
      keratomileusis for the correction of high myopia.
AB  - PURPOSE: To evaluate efficacy, predictability, stability and safety of adjustable
      refractive surgery (ARS) by combining a phakic intraocular lens (IOL) (Artisan
      lens 6-mm optical zone [OZ]) and laser in situ keratomileusis (LASIK) (6.5 mm OZ)
      for the correction of myopia greater than -15.00 diopters (D). DESIGN:
      Noncomparative interventional case series. PARTICIPANTS: Twenty-six eyes of 18
      patients with a preoperative spherical equivalent between -16.00 and -23.00 D.
      METHODS: First surgery: An 8.5/9.5-mm flap was created and a 6-mm optic iris claw
      phakic IOL of -15.00 D was inserted in the anterior chamber through a posterior
      corneal incision. The second surgery was performed once refraction and topography
      were stable, between 3 and 5 months later. Second surgery: LASIK enhancement (6.5
      9.2 OZ); the flap was relifted, and the residual refractive error was corrected.
      MAIN OUTCOME MEASURES: The main parameters in this study were uncorrected visual
      acuity, best-corrected visual acuity (BCVA), refraction, contrast sensitivity,
      endothelial cell count (ECC), and subjective response. RESULTS: Twenty-eight
      months after both surgeries, 80.70% of the eyes were within 0.50 D of emmetropia
      and 100% within 1.0 D. Twenty-six percent of the eyes gained 3 or more lines from
      their preoperative BCVA, and 42% gained 2 or more lines. There was no visual loss
      in any eye from 6 weeks to 24 months after LASIK enhancement (second surgery) and
      refraction, and visual acuities remained stable. Two subjects (11%) had some
      subjective disturbances at night. There was a 0.61% mean loss of ECC during the
      first 12 months and a 0.60% loss during the next 16 months. No serious
      complications were observed. CONCLUSIONS: ARS with the combination of a 6-mm
      optic, 15 D Artisan lens, and LASIK appears to be a safe and highly predictable
      method for the correction of myopia greater than -15.00 D. It is the best
      approach with the technology currently available.

PMID- 11320027
TI  - Late natural history of corneal topography after excimer laser photorefractive
      keratectomy.
AB  - PURPOSE: To investigate the 3 month to 1 year natural history of corneal
      topography after excimer laser photorefractive keratectomy (PRK). DESIGN: A
      prospective, multicenter, nonrandomized comparative study. PARTICIPANTS: A total
      of 75 eyes of 68 patients with myopia were studied. INTERVENTION: Excimer laser
      photorefractive keratectomy and computer-assisted videokeratography were
      performed. MAIN OUTCOME MEASURES: Preoperative and 3, 6, and 12 month
      postoperative topography patterns were compared and changes assessed by averaging
      defined sectors of the ablation zone in individual maps to produce composite
      "average" topography maps. RESULTS: Corneal topography was relatively smooth 3
      months after PRK. By 12 months, the corneal contour in general had become even
      more uniform. No "central island" effect was observed. When looking at right and
      left eyes independently, there was a tendency toward maximum flattening nasally.
      CONCLUSIONS: Corneal topography in general continues to smooth from 3 to 12
      months after PRK, possibly as a result of epithelial and stromal healing and
      remodeling. Right and left eyes on average show mirror-image, spatially oriented
      topography patterns.

PMID- 11320028
TI  - Cause-specific prevalence of bilateral visual impairment in Victoria, Australia:
      the Visual Impairment Project.
AB  - PURPOSE: To study the cause-specific prevalence of eye diseases causing bilateral
      visual impairment in Australian adults. DESIGN: Two-site, population-based cross
      sectional study. PARTICIPANTS: Participants were aged 40 years and older and
      resident in their homes at the time of recruitment for the study. The study was
      conducted during 1992 through 1996. METHODS: The study uses a cluster stratified
      random sample of 4744 participants from two cohorts, urban, and rural Victoria.
      Participants completed a standardized interview and eye examination, including
      presenting and best-corrected visual acuity, visual fields, and dilated ocular
      examination. The major cause of vision loss was identified for all participants
      found to be visually impaired. Population-based prevalence estimates are weighted
      to reflect the age and gender distribution of the two cohorts in Victoria. MAIN
      OUTCOME MEASURES: Visual impairment was defined by four levels of severity on the
      basis of best-corrected visual acuity or visual field: <6/18 > or =6/60 and/or
      <20 degrees > or =10 degrees radius field, moderate vision impairment; severe
      vision impairment, <6/60 > or =3/60 and/or <10 degrees > or =5 degrees radius
      field; and profound vision impairment <3/60 and/or <5 degrees radius field. In
      addition, less-than-legal driving vision, <6/12 > or =6/18, and/or homonymous
      hemianopia were defined as mild vision impairment. In Australia, legal blindness
      includes severe and profound vision impairment. RESULTS: The population-weighted
      prevalence of diseases causing less-than-legal driving or worse impairment in the
      better eye was 42.48/1000 (95% confidence interval [CI], 30.11, 54.86).
      Uncorrected refractive error was the most frequent cause of bilateral vision
      impairment, 24.68/1000 (95% CI, 16.12, 33.25), followed by age-related macular
      degeneration (AMD), 3.86/1000 (95% CI, 2.17, 5.55); other retinal diseases,
      2.91/1000 (95% CI, 0.74, 5.08); other disorders, 2.80/1000 (95% CI, 1.17, 4.43);
      cataract, 2.57/1000 (95% CI, 1.38, 3.76); glaucoma, 2.32/1000 (95% CI, 0.72,
      3.92); neuro-ophthalmic disorders, 1.80/1000 (95% CI, 0, 4.11); and diabetic
      retinopathy, 1.53/1000 (95% CI, 0.71, 2.36). The prevalence of legal blindness
      was 5.30/1000 (95% CI, 3.24, 7.36). Although not significantly different, the
      causes of legal blindness were uncorrected refractive errors, AMD, glaucoma,
      other retinal conditions, and other diseases. CONCLUSIONS: Significant reduction
      of visual impairment may be attained with the application of current knowledge in
      refractive errors, diabetes mellitus, cataract, and glaucoma. Although easily
      preventable, uncorrected refractive error remains a major cause of vision
      impairment.

PMID- 11320029
TI  - Sensitivity and specificity of tests to detect eye disease in an older
      population.
AB  - OBJECTIVE: To compare the ability of tests of visual function to detect the
      presence of eye disease. DESIGN: Cross-sectional study. PARTICIPANTS: Three
      thousand six hundred fifty-four of 4433 (82.4%) eligible residents of an area
      near Sydney aged 49 years and older had a detailed eye examination, including
      retinal and lens photography and subsequent grading of eye disease, tests of
      presenting and corrected visual acuity, contrast sensitivity, screening visual
      field and intraocular pressure. MAIN OUTCOME MEASURES: Receiver operator
      characteristic (ROC) curves were created and area under the curve compared for
      each vision test. Sensitivity and specificity were calculated for each test.
      RESULTS: No single vision test predicted the presence of eye disease with any
      consistency. Best-corrected visual acuity or contrast sensitivity had the highest
      area under the ROC curve for most eye diseases examined but had poor sensitivity
      and specificity. For glaucoma and diabetic retinopathy there was no difference in
      area under the curve for any of the tests examined, and no test had a good
      balance of sensitivity and specificity. Screening tests (performed with
      presenting correction) did not perform as well as nonscreening tests (those
      carried out after refraction with best correction). CONCLUSIONS: Current vision
      tests are not particularly good at detecting eye disease compared with the "gold
      standard" of a full eye examination performed by an ophthalmologist. Further work
      in this area should be carried out before vision screening programs can be
      recommended for implementation among older people.

PMID- 11320030
TI  - Microsporidial keratoconjunctivitis in a healthy contact lens wearer without
      human immunodeficiency virus infection.
AB  - PURPOSE: To present a rare case of microsporidial keratoconjunctivitis in an
      otherwise healthy contact lens wearer without human immunodeficiency virus
      infection who responded to treatment with systemic albendazole and topical
      fumagillin. DESIGN: Interventional case report. METHOD: A cornea epithelial
      scraping from a man with unilateral keratoconjunctivitis previously treated with
      topical steroids was evaluated by modified trichome staining. MAIN OUTCOME
      MEASURES: The patient was evaluated for his symptoms, visual acuity, clinical
      observations, and pathologic examination of corneal scrapes. RESULTS: Modified
      trichome staining of an epithelial corneal scraping revealed pinkish to red
      organisms characteristic of microsporidia. Results of a human immunodeficiency
      virus (HIV) enzyme-linked immunosorbent assay test were negative. The symptoms of
      ocular discomfort and clinical signs of keratoconjunctivitis resolved after 2
      months of treatment with albendazole and topical fumagillin. CONCLUSIONS: Ocular
      infection with microsporidia, although classically occurring in patients with HIV
      infection, may occur rarely in healthy individuals, especially if previously
      treated with systemic immune suppression or topical steroids. Microsporidial
      keratoconjunctivitis should be considered in the differential diagnosis of a
      contact lens wearer with atypical multifocal diffuse epithelial keratitis.

PMID- 11320031
TI  - Conjunctival lymphoid tumors: clinical analysis of 117 cases and relationship to
      systemic lymphoma.
AB  - OBJECTIVE: To investigate the clinical features of conjunctival lymphoid tumors
      and factors predictive of systemic lymphoma. DESIGN: Retrospective, observational
      case series. SETTING: Clinical practice of ocular oncology. PARTICIPANTS: The
      participants included 117 consecutive patients with lymphoid tumors of the
      conjunctiva treated at the Oncology Service of Wills Eye Hospital between 1974
      and 1999. MAIN OUTCOME MEASURE: The main outcome measure was the development of
      systemic lymphoma. Cox proportional regression models were used to calculate the
      risk of eventual systemic lymphoma. Kaplan-Meier survival estimates were used to
      analyze the development of systemic lymphoma as a function of time. RESULTS:
      There were 55 males (47%) and 62 females (53%); 110 patients (94%) were white and
      7 patients (6%) were African AMERICAN: The mean age at ocular presentation was 61
      years, and the conjunctival lymphoid infiltrate was unilateral in 72 patients
      (62%) and bilateral in 45 patients (38%). In 8 patients (7%), initial unilateral
      conjunctival disease evolved into bilateral involvement over a mean of 32 months.
      Additional sites of ocular involvement were found in 27 patients (23%) and
      included lymphoid tumor in the eyelid in 3 cases, orbit in 18, choroid in 5, and
      vitreous in 1. Systemic lymphoma was known to exist before ocular diagnosis in 16
      patients; (14%; for a mean of 51 months) and was found subsequent to ocular
      diagnosis in 20 patients (17; at a mean of 21 months). Therefore, of 117 patients
      with conjunctival lymphoid infiltration, 36 (31%) had or eventually developed
      systemic lymphoma, and 81 (69%) did not manifest systemic lymphoma during the
      mean follow-up of 38 months. Of the 64 patients with unilateral conjunctival
      involvement, 11 (17%) manifested systemic lymphoma, and of the 53 patients with
      bilateral involvement, 25 (47%) manifested systemic lymphoma. By univariate
      analysis, the clinical factors at date first seen predictive of the presence or
      development of systemic lymphoma included location of the tumor at an extralimbal
      site (fornix or midbulbar conjunctiva; P = 0.02) and increasing number of
      conjunctival tumors (P = 0.02). Using Kaplan-Meier life table analysis of those
      101 patients who had conjunctival lymphoid tumor(s) and no evident systemic
      lymphoma at presentation, systemic lymphoma was eventually discovered in 7% of
      patients at 1 year, 12% at 2 years, 15% at 5 years, and 28% at 10 years. Overall,
      only one patient (<1%) died of systemic lymphoma, at 28 months after the
      diagnosis of the ocular disease. CONCLUSIONS: Lymphoid tumors of the conjunctiva
      are associated with systemic lymphoma in 31% of patients. Systemic lymphoma is
      found more often in those patients with forniceal or midbulbar conjunctival
      involvement and in those with multiple conjunctival tumors. Long-term systemic
      follow-up is advised, because related systemic lymphoma can manifest many years
      later.

PMID- 11320033
TI  - Primary and secondary transconjunctival involutional entropion repair.
AB  - PURPOSE: Lower eyelid involutional entropion is a significant disorder of the
      aging population resulting from horizontal eyelid laxity, overriding orbicularis
      oculi muscle, and attenuation of the lower eyelid retractors. The purpose of this
      study is to describe the long-term results of transconjunctival entropion repair.
      DESIGN: Interventional noncomparative case series. PARTICIPANTS: Thirty-six
      eyelids in 31 patients. METHODS: Charts were reviewed of all transconjunctival
      entropion repairs, which included myectomy, retractor fixation, and horizontal
      shortening performed by three oculoplastic surgeons between January 1993 and
      January 1999. Cases with less than 12 months follow-up were excluded. MAIN
      OUTCOME MEASURES: Entropion recurrence. RESULTS: Thirty-six lids in 31 patients
      were followed for mean of 31.5 months (12.5-79). Six of 36 lids (16.7%) had
      postoperative complications. Recurrent entropion occurred in 3 of 36 lids (8.3%)
      an average 16.3 months (7-35) after surgery. An average of 6 trichiasis lashes (1
      10) occurred in 4 of 36 lids (11.1%) at a mean of 2.25 months (1-4) after
      surgery. There were no overcorrections. Three of 36 lids (8.3%) required
      additional surgery. CONCLUSIONS: Entropion recurrence after three-step
      transconjunctival repair is within the 0% to 30% reported recurrence for other
      repair techniques but more frequent than reported for a similar transcutaneous
      procedure. The 8.3% recurrence rate might have resulted from inadequate myectomy,
      inadequate retractor fixation, cicatricial changes directly related to the
      transconjunctival incision, or progressive involutional changes. Trichiasis was
      the most frequent complication. Transconjunctival entropion repair may be
      slightly less effective than transcutaneous repair.

PMID- 11320032
TI  - Proliferative activity and p53 expression in primary and recurrent pterygia.
AB  - PURPOSE: To assess p53 expression and proliferative activity in primary and
      recurrent pterygia from the same eyes. DESIGN: Retrospective comparative human
      tissue study. PARTICIPANTS: Tissue from excised primary pterygia that did not
      recur (group A, n = 10) was compared with tissue from primary pterygia that
      recurred (group B, n = 10) and to the recurrent pterygia tissue that was excised
      from subjects in group B (group C, n = 10). Ten normal conjunctivas served as
      controls (group D). METHODS: Sections from each pterygium were immunostained with
      the MIB-1 and bp53. 12 monoclonal antibodies that react with Ki-67 and p53
      antigens, respectively. MAIN OUTCOME MEASURES: Proliferative activity was
      calculated as the mean of the MIB-1 positive cell count per eyepiece grid in high
      magnification (x40) (positive cell count/grid). Percentage of positive cells of
      all cells in the grid area was evaluated in the p53-stained sections. RESULTS:
      Proliferative activity was found in the epithelium overlying the pterygia and
      normal conjunctiva. The mean MIB-1 positive cell count/grid +/- standard error
      was 2.84 +/- 1.07, 1.74 +/- 0.82, 3.83 +/- 1.35, and 0.86 +/- 0.33 in groups A,
      B, C, and D, respectively (P = 0.17, Kruskal-Wallis). P53 staining was found in
      50% of pterygia in groups A, B, and C; none of the normal conjunctival tissues
      showed p53 immunoreactivity. Four of five p53-positive tissues in group B were
      p53-negative in group C. In the p53-positive pterygia, less than 10% of cells
      were p53 positive. However, p53-positive pterygia had higher mean MIB-1 positive
      cell count/grid +/- standard error as compared with the p53-negative lesions,
      4.56 +/- 0.94 vs 1.39 +/- 0.59 (P = 0.021, Mann-Whitney). CONCLUSIONS: p53
      immunoreactivity and high proliferative activity in the epithelium overlying the
      pterygium are not associated with recurrence of pterygium.

PMID- 11320034
TI  - Canalicular stenosis secondary to docetaxel (taxotere): a newly recognized side
      effect.
AB  - OBJECTIVE: To report a newly recognized side effect of a commonly used
      antineoplastic agent, docetaxel, in three patients with metastatic breast cancer.
      DESIGN: Observational case reports. PARTICIPANTS: Three patients with metastatic
      breast cancer who received weekly docetaxel chemotherapy. MAIN OUTCOME MEASURES:
      Occurrence of epiphora and severity of punctal and canalicular fibrosis secondary
      to docetaxel. RESULTS: In three patients receiving weekly docetaxel, canalicular
      stenosis and resultant epiphora developed shortly after start of their treatment.
      Discontinuation of drug several months after initiation of therapy did not lead
      to resolution of symptoms in two of the three patients. CONCLUSIONS: Epiphora is
      a newly recognized side effect of docetaxel and may occur more frequently with
      weekly cycles of this drug. The mechanism for epiphora seems to be punctal and
      canalicular stenosis. This side effect, in advanced cases, is not reversible with
      discontinuation of the drug. Patients being administered weekly cycles of
      docetaxel should be screened for epiphora and canalicular stenosis, and treatment
      in the form of silicone intubation or punctoplasty should be considered in early
      stages to prevent the need for conjunctivodacryocystorhinostomy.

PMID- 11320035
TI  - Microcirculation patterns other than loops and networks in choroidal and ciliary
      body melanomas.
AB  - PURPOSE: To provide ophthalmologists and pathologists with expanded criteria for
      separating patients at high risk of metastatic melanoma from those at low risk on
      the basis of microcirculation patterns in choroidal and ciliary body melanomas.
      DESIGN: Tissue culture studies and observational case series. PARTICIPANTS: The
      pattern-forming ability of four uveal melanoma cell lines of varying degrees of
      aggressive behavior was studied in vitro. Histologic sections of 234 eyes removed
      for choroidal or ciliary body melanoma were studied for the presence of
      microcirculation patterns. METHODS: The study was divided into two phases: the
      study of histologic sections of eyes removed for choroidal and ciliary body
      melanomas and observations on the in vitro behavior of cultured melanoma cells of
      varying degrees of invasive behavior. The presence or absence of each of nine
      microcirculation patterns was recorded from tissue sections, and
      interrelationships between different patterns were explored statistically. In
      vitro reconstitution of patterns and a study of the interrelationships of
      patterns in histologic sections was carried out. In the in vitro studies, uveal
      melanoma cell lines of varying degrees of aggressive potential were cultured to
      observe the development of architectural patterns other than loops and networks.
      MAIN OUTCOME MEASURES: In histologic studies, the outcome measure was the
      conditional probability of detecting loops or networks given the presence or
      absence of other patterns positive for periodic acid-SCHIFF: For tissue culture
      studies, the outcome measure was either the development or lack of development of
      patterns of different shapes in vitro. RESULTS: Histologic studies disclosed that
      given the presence of arcs without or with branching in a tissue section, it is
      likely that loops or networks will be detected in the same section plane,
      suggesting that the production of these patterns by aggressive tumor cells
      reflects a spectrum of architectural potential. In vitro studies confirmed this
      hypothesis by revealing that highly aggressive and metastatic uveal melanoma cell
      lines, but not poorly aggressive tumor cell lines, generated parallel channels
      with and without crosslinking and arcs with and without branching as well as
      loops and networks. CONCLUSIONS: The criteria for separating patients into low-
      and high-risk categories for metastasis from uveal melanoma should be expanded to
      include patterns other than loops or networks. In both the pathology laboratory
      as well as in a clinical setting, the detection of arcs or arcs with branching
      and parallel channels should prompt a careful search for loops and networks and
      for crosslinking parallel channels, respectively.

PMID- 11320036
TI  - Management of the neonate with symptomatic congenital heart disease.

PMID- 11320038
TI  - High or low oxygen saturation for the preterm baby.

PMID- 11320037
TI  - Critical haemoglobin thresholds in premature infants.

PMID- 11320039
TI  - Ultrasound diagnosis and neurodevelopmental outcome of localised and extensive
      cystic periventricular leucomalacia.
AB  - AIMS: To compare the ultrasound (US) evolution and neurodevelopmental outcome of
      infants with localised (grade II) and extensive (grade III) cystic
      periventricular leucomalacia (c-PVL). METHODS: Over a nine year period, c-PVL was
      diagnosed in 96/3451 (2.8%) infants in two hospital cohorts. Eighteen were
      excluded from the study. Thirty nine infants with grade II PVL were compared with
      39 infants with grade III PVL. RESULTS: The two populations were comparable for
      gestational age and birth weight. In infants with grade II PVL, cysts were noted
      to develop more often after the first month of life (53%) in contrast with grade
      III PVL (22%) (odds ratio (OR) 3.81 (95% confidence interval (CI) 1.19 to
      12.63)). Cysts were also more often unilateral in grade II (54%) than in grade
      III PVL (0%) (OR indefinite; RR 3.17 (95% CI 2.16 to 4.64)). At 40 weeks
      postmenstrual age (PMA), cysts were no longer seen on US in 13/38 infants with
      grade II PVL, with ventriculomegaly being the only visible sequel in nine cases.
      In grade III PVL, cysts were still present in 25 of the 27 surviving infants.
      Nine infants with grade II PVL were free of motor sequelae at follow up compared
      with one infant with grade III PVL (OR 8.07 (95% CI 0.92 to 181.66)). Twenty two
      out of 29 children with grade II PVL who developed cerebral palsy achieved
      independent walking compared with 3/26 with grade III PVL (OR 75 (95% CI 11.4 to
      662)). CONCLUSIONS: In the cohort studied, 50% of the infants with c-PVL had a
      more localised form (grade II). In grade II PVL, the cysts developed beyond the
      first month of life in more than half of the cases and were often no longer
      visible, on US, at 40 weeks PMA. In order not to miss this diagnosis, sequential
      US should also be performed beyond the first month of life. Mild ventriculomegaly
      noted at term can sometimes be due to grade II c-PVL. Cerebral palsy was slightly
      less common and tended to be less severe in infants with grade II PVL than in
      those with grade III PVL.

PMID- 11320040
TI  - Community based universal neonatal hearing screening by health visitors using
      otoacoustic emissions.
AB  - OBJECTIVES: To carry out a pilot study to test the feasibility of health visitors
      (HVs) performing neonatal otoacoustic emissions (OAE) hearing screening in the
      community using Echoport ILO288 and to evaluate its acceptability to parents and
      HVs. DESIGN: Prospective cohort study. SETTING: Local health centres and babies'
      homes in urban and rural settings in West Gloucestershire. PARTICIPANTS: Twelve
      HVs, 683 babies, and their parents. MAIN OUTCOME MEASURES: Coverage rate, age at
      testing, referral rate for formal audiology testing, and parental anxiety scores.
      RESULTS: Of the 683 babies registered with the study HVs, 99% (675) were tested,
      with a median age at first test of 18 days. Parental consent for the study was
      refused for six of the eight not tested. Taking a unilateral pass as a screening
      pass (for comparison with other studies), 4% (27/675) failed the first OAE test,
      and 1.9% (13/675) failed a second OAE test performed by the HV within a further
      two weeks and were referred for formal audiology testing. One baby (0.15%) was
      found to have a moderate sensorineural hearing loss on brain stem auditory evoked
      responses, giving a false positive rate of 1.7% (12/675). Some 18% (120/675) were
      tested at home, of which 80% (96/120) were combined with another planned reason
      for HV contact. In all, 82% (555/675) of tests were carried out in health centre
      clinics, of which 47% (260/555) were combined purpose visits. Mean parental
      anxiety scores (possible range 0-5) were 0.86, 2.27, and 3.45 before the first
      test, first retest, and audiology test respectively. The median time taken for
      one HV to complete testing was 12.2 minutes (range 3-65), compared with the 15
      minutes currently allocated for two HVs to perform distraction testing. Based on
      the results of questionnaires, the test was very well received by parents and HVs
      alike. CONCLUSION: HVs are able to perform OAE testing in the neonatal period at
      home and in local health centre clinics. They achieve high population coverage
      rates and low false positive rates. Universal neonatal hearing screening by HVs
      using OAE testing is feasible, well received, and could be less demanding of HV
      time than the current distraction testing. This model of universal neonatal
      hearing screening should be considered by the National Screening Committee.

PMID- 11320041
TI  - Background electroencephalographic (EEG) activities of very preterm infants born
      at less than 27 weeks gestation: a study on the degree of continuity.
AB  - AIMS: To clarify the features of the background electroencephalographic (EEG)
      activities in clinically well preterm infants born at less than 27 weeks
      gestation and to outline their chronological changes with increasing
      postconceptional age (PCA). METHODS: EEGs of clinically well premature infants
      born at less than 27 weeks gestation were recorded during the early postnatal
      period. The infants were separated into three groups according to their PCA at
      the time of EEG recording (21-22 weeks PCA, 23-24 weeks PCA, and 25-26 weeks
      PCA). The mean and maximum duration of interburst intervals (IBIs), the mean
      duration of bursts, and the percentage of continuous and discontinuous patterns
      in each PCA group were evaluated. RESULTS: There were three infants at 21-22
      weeks PCA, seven at 23-24 weeks PCA, and five at 25-26 weeks PCA. Eighteen EEG
      recordings were obtained. The mean and maximum IBI duration decreased with
      increasing PCA. The percentage of continuous patterns increased with increasing
      PCA. Conversely, the percentage of discontinuous patterns decreased with
      increasing PCA. CONCLUSIONS: In premature infants born at less than 27 weeks
      gestation, the characteristics of the background EEG activities were similar to
      those of older premature infants. These changes reflect the development of the
      central nervous system in this period.

PMID- 11320042
TI  - Type I collagenases in bronchoalveolar lavage fluid from preterm babies at risk
      of developing chronic lung disease.
AB  - OBJECTIVE: To assess whether increased collagenolysis precedes severe chronic
      lung disease (CLD). METHODS: Matrix metalloproteinase-1 (MMP-1) and MMP-8
      (enzymes that degrade type I collagen, the main structural protein of lung
      extracellular matrix) were measured by enzyme linked immunosorbent assay in 100
      bronchoalveolar lavage samples taken during the first 6 postnatal days from 45
      ventilated preterm babies < 33 weeks gestation. The median value for each baby
      was calculated. CLD was defined as an oxygen requirement after the 36th week
      after conception. RESULTS: MMP-8 levels in bronchoalveolar lavage fluid were
      higher (median 13 ng/ml) in 20 babies who developed CLD than in 25 without CLD
      (median 2 ng/ml). No MMP-1 was detected in any sample. CONCLUSIONS: MMP-8 can be
      detected in bronchoalveolar lavage fluid from preterm babies, and higher levels
      are found in those who later develop CLD. MMP-8 may contribute to lung injury
      that occurs as a prelude to CLD.

PMID- 11320043
TI  - A trial of recombinant human granulocyte colony stimulating factor for the
      treatment of very low birthweight infants with presumed sepsis and neutropenia.
AB  - OBJECTIVES: The primary objective was to investigate the safety of recombinant
      human granulocyte colony stimulating factor (rhG-CSF) for the treatment of very
      low birthweight infants (VLBW) with sepsis and relative neutropenia, specifically
      with regard to worsening of respiratory distress and thrombocytopenia and all
      cause mortality. Secondary objectives were to evaluate duration of ventilation,
      intensive care, and antibiotic use as markers of efficacy. DESIGN: Neonates (< or
      = 28 days) in intensive care, with birth weights of 500-1500 g, absolute
      neutrophil count (ANC) of < or = 5 x 10(9)/l, and clinical evidence of sepsis,
      were randomly assigned to receive either rhG-CSF (10 microg/kg/day) administered
      intravenously (n = 13), or placebo (n = 15) for a maximum of 14 days, in addition
      to standard treatment and antibiotics. All adverse events, oxygenation index,
      incidence of thrombocytopenia, all cause mortality, duration of ventilation,
      intensive care and antibiotic treatment, and ANC recovery were compared between
      the two groups. RESULTS: Adverse events and oxygenation index were not increased
      by, and thrombocytopenia was not attributable to, treatment with rhG-CSF. At 6
      and 12 months postmenstrual age, there were significantly fewer deaths in the
      group receiving rhG-CSF (1/13 v 7/15; p < or = 0.038). There was a non
      significant trend towards a reduction in duration of ventilation, intensive care,
      and antibiotic use in the rhG-CSF group. There was a significantly more rapid
      increase in ANC in the rhG-CSF treated babies (p < 0.001). CONCLUSIONS: In a
      small randomised placebo controlled trial in a highly selected group of neonates,
      adjuvant treatment with rhG-CSF increased ANC rapidly, and no treatment related
      adverse events were identified. Mortality at 6 and 12 months postmenstrual age
      was significantly lower in the treatment group. A large trial investigating
      efficacy in a similar group of neonates is warranted.

PMID- 11320044
TI  - Randomised controlled study of oral erythromycin for treatment of
      gastrointestinal dysmotility in preterm infants.
AB  - AIM: To evaluate the effectiveness of oral erythromycin as a prokinetic agent for
      the treatment of moderately severe gastrointestinal dysmotility in preterm very
      low birthweight infants. METHODS: A prospective, double blind, randomised,
      placebo controlled study in a tertiary referral centre of a university teaching
      hospital was conducted on 56 preterm infants (< 1500 g) consecutively admitted to
      the neonatal unit. The infants were randomly allocated by minimisation to receive
      oral erythromycin (12.5 mg/kg, every six hours for 14 days) or an equivalent
      volume of placebo solution (normal saline) if they received less than half the
      total daily fluid intake or less than 75 ml/kg/day of milk feeds by the enteral
      route on day 14 of life. The times taken to establish half, three quarters, and
      full enteral feeding after the drug treatment were compared between the two
      groups. Potential adverse effects of oral erythromycin and complications
      associated with parenteral nutrition were assessed as secondary outcomes.
      RESULTS: Twenty seven and 29 infants received oral erythromycin and placebo
      solution respectively. The times taken to establish half, three quarters, and
      full enteral feeding after the drug treatment were significantly shorter in the
      group receiving oral erythromycin than in those receiving the placebo (p < 0.05,
      p < 0.05 and p < 0.0001 respectively). There was also a trend suggesting that
      more infants with prolonged feed intolerance developed cholestatic jaundice in
      the placebo than in the oral erythromycin group (10 v 5 infants). None of the
      infants receiving oral erythromycin developed cardiac dysrhythmia, pyloric
      stenosis, or septicaemia caused by multiresistant organisms. CONCLUSIONS: Oral
      erythromycin is effective in facilitating enteral feeding in preterm very low
      birthweight infants with moderately severe gastrointestinal dysmotility. Treated
      infants can achieve full enteral feeding 10 days earlier, and this may result in
      a substantial saving on hyperalimentation. However, until the safety of
      erythromycin has been confirmed in preterm infants, this treatment modality
      should remain experimental. Prophylactic or routine use of this medication for
      treatment of mild cases of gastrointestinal dysmotility is probably not warranted
      at this stage.

PMID- 11320045
TI  - Randomised controlled trial of prophylactic etamsylate: follow up at 2 years of
      age.
AB  - AIM: To assess the role of etamsylate in reducing the risk of haemorrhagic brain
      damage and its consequences. DESIGN: Follow up of babies recruited into a
      randomised controlled trial. METHODS: A total of 334 infants born before 33 weeks
      gestation in France and Greece were randomly allocated within the first four
      hours of birth either to receive etamsylate or to act as controls. The principal
      outcomes in the trial were death or impairment and/or disability at the age of 2
      years. RESULTS: Fifty nine children were lost to follow up. A total of 115 (34%)
      either died or had some impairment or disability, and 88 (26%) either died or had
      severe impairment or disability at 2 years of age. These outcomes did not differ
      significantly between the two randomised groups: relative risks and 95%
      confidence intervals 1.14 (0.78 to 1.4) and 1.17 (0.82 to 1.68) respectively. The
      findings were similar for all the prespecified subgroup analyses stratified by
      key prognostic factors at trial entry: country of birth, gestational age < or
      >or= 29 weeks, inborn or outborn, age < or >or= 1 hour, and with or without
      cerebral scan abnormality. CONCLUSION: These findings do not support the use of
      etamsylate. Other strategies need to be evaluated for the prevention of mortality
      and morbidity in these vulnerable infants.

PMID- 11320046
TI  - Blood transfusion increases radical promoting non-transferrin bound iron in
      preterm infants.
AB  - BACKGROUND: Blood transfusion has been recognised as a risk factor for the
      development of retinopathy of prematurity (ROP) or chronic lung disease (CLD) in
      preterm infants, but the precise mechanism involved is not understood. AIM: To
      investigate the level of non-transferrin bound "free" iron, which has the
      potential to promote the generation of reactive oxygen species, and its redox
      status in the plasma of preterm infants immediately before and after blood
      transfusion. METHODS: Twenty one preterm infants with a median gestational age
      and birth weight of 27 weeks and 1021 g respectively were prospectively enrolled
      in the study. Sixteen of the 21 infants developed ROP and/or CLD. The infants
      were transfused with concentrated red blood cells at a median age of 32 days. The
      plasma concentration of total bleomycin detectable iron (BDI) was measured and
      also the ferrous iron (Fe(2+)) activity by bleomycin-iron complex dependent
      degradation of DNA. RESULTS: Even before blood transfusion, BDI was detectable in
      one third of the blood samples, and all but one sample had ferrous iron activity.
      After transfusion, both BDI and ferrous iron activity were significantly
      increased, in contrast with the situation in full term infants. Plasma ascorbic
      acid (AA) concentration was significantly decreased after blood transfusion,
      whereas the level of its oxidation product, dehydroascorbic acid (DHAA), and the
      DHAA/AA ratio were significantly increased compared with before the transfusion.
      The activity of plasma ferroxidase, which converts iron from the ferrous to the
      ferric state, was appreciably decreased in preterm infants, as expected from
      their very low plasma caeruloplasmin concentration. CONCLUSIONS: Plasma non
      transferrin bound iron was significantly increased in preterm infants after blood
      transfusion and existed partly in the ferrous form, because of the low
      ferroxidase activity and the reduction of ferric iron (Fe(3+)) by ascorbic acid.
      This finding was specific to preterm infants and was not observed in full term
      infants after blood transfusion. Non-transferrin bound "free" iron may catalyse
      the generation of reactive oxygen species, which may be responsible for the
      clinical association of blood transfusion with ROP and CLD.

PMID- 11320047
TI  - Improved survival and neurodevelopmental outcome after prolonged ventilation in
      preterm neonates who have received antenatal steroids and surfactant.
AB  - AIMS: To assess survival and neurodevelopmental outcome following prolonged
      ventilation beyond 27 or 49 days of postnatal life in neonates treated with
      antenatal steroids and surfactant. METHODS: The medical records of 84 babies born
      in 1994-1996 requiring ventilation after 27 postnatal days at Liverpool Women's
      Hospital were reviewed to determine the duration of mechanical ventilation,
      survival, and neurodevelopmental outcome at 3 years of age. RESULTS: Fifty six
      babies were mechanically ventilated after 27 postnatal days but for less than 50
      days; 48 (86%) survived to 3 years. Twenty six (54%) of the survivors had normal
      neurodevelopment at 3 years and seven (15%) had only mild disability. Twenty
      eight babies were ventilated after 49 postnatal days; 14 survived to 3 years.
      Five of these survivors were neurodevelopmentally normal at 3 years and two had
      mild disability. CONCLUSIONS: Survival decreases with more prolonged ventilation.
      When antenatal steroids and postnatal surfactant are used, there appears to be
      improved survival and neurodevelopmental outcome in preterm babies who require
      prolonged ventilation.

PMID- 11320048
TI  - An unusual cause of respiratory distress: unilateral pulmonary agenesis.

PMID- 11320049
TI  - Neonatal thrombocytosis resulting from the maternal use of non-narcotic
      antischizophrenic drugs during pregnancy.
AB  - Neonatal thrombocytosis can result from maternal narcotic drug abuse. The case of
      a male infant is reported who was born to a woman with schizophrenia treated with
      non-narcotic psychotropic drugs during pregnancy; he developed severe prolonged
      thrombocytosis. The platelet count reached 1310 x 10(9)/l on day 15. This
      thrombocytosis persisted for three months. The patient was treated with
      dipyridamole. A bone marrow aspirate showed normal myeloid and erythroid
      precursors with an increased number of megakaryocytes. Plasma concentrations of
      interleukin 6 and thrombopoietin were suppressed. No obvious complications from
      the thrombocytosis occurred, and the platelet count fell to within the upper
      limit of normal after 3 months of age. This case indicates that thrombocytosis
      may occur in infants born to mothers treated with non-narcotic
      psychopharmaceutical drugs during pregnancy. The thrombocytosis in this case may
      have been induced by factors other than interleukin 6 or thrombopoietin.

PMID- 11320050
TI  - Hepatitis C in pregnancy.

PMID- 11320051
TI  - Detection of inborn errors of metabolism in the newborn.

PMID- 11320053
TI  - Dr Edward Rigby, junior, of London (1804-1860) and his system of midwifery.

PMID- 11320054
TI  - Glypicans in growth control and cancer.
AB  - The name glypican has been assigned to a family of heparan sulfate (HS)
      proteoglycans that are linked to the cell membrane by a glycosyl
      phosphatidylinositol anchor. To date, six family members of this family have been
      identified in mammals (GPC1 to GPC6) and two in Drosophila. Glypicans are
      expressed predominantly during development, and they are thought to play a role
      in morphogenesis. As HS-carrying molecules, glypicans were initially considered
      potential regulators of heparin-binding growth factors. This has been recently
      confirmed by genetic interaction experiments showing that glypicans regulate
      wingless signaling in Drosophila. The involvement of glypicans in the in vivo
      regulation of other heparin-binding growth factors, such as fibroblast growth
      factors, remains to be determined. Interestingly and unexpectedly, a role for
      GPC3 in the regulation of insulin-like growth factors has been proposed. This
      hypothesis is based on the phenotype of patients with Simpson-Golabi-Behmel
      syndrome (SGBS), an overgrowth and dysmorphic syndrome in which the GPC3 gene is
      mutated. Thus, it is possible that glypicans regulate different kinds of growth
      factors in a tissue-specific manner. In addition to its involvement in SGBS, down
      regulation of GPC3 has been recently associated with the progression of several
      types of malignant tumors, including mesotheliomas and ovarian cancer. A role for
      GPC1 in pancreatic cancer progression has also been proposed.

PMID- 11320052
TI  - Nucleated red blood cells in the fetus and newborn.

PMID- 11320055
TI  - Formation of the glycan chains in the synthesis of bacterial peptidoglycan.
AB  - The main structural features of bacterial peptidoglycan are linear glycan chains
      interlinked by short peptides. The glycan chains are composed of alternating
      units of N-acetylglucosamine (GlcNAc) and N-acetylmuramic acid (MurNAc), all
      linkages between sugars being beta,1-->4. On the outside of the cytoplasmic
      membrane, two types of activities are involved in the polymerization of the
      peptidoglycan monomer unit: glycosyltransferases that catalyze the formation of
      the linear glycan chains and transpeptidases that catalyze the formation of the
      peptide cross-bridges. Contrary to the transpeptidation step, for which there is
      an abundant literature that has been regularly reviewed, the transglycosylation
      step has been studied to a far lesser extent. The aim of the present review is to
      summarize and evaluate the molecular and cellullar data concerning the formation
      of the glycan chains in the synthesis of peptidoglycan. Early work concerned the
      use of various in vivo and in vitro systems for the study of the polymerization
      steps, the attachment of newly made material to preexisting peptidoglycan, and
      the mechanism of action of antibiotics. The synthesis of the glycan chains is
      catalyzed by the N-terminal glycosyltransferase module of class A high-molecular
      mass penicillin-binding proteins and by nonpenicillin-binding monofunctional
      glycosyltransferases. The multiplicity of these activities in a given organism
      presumably reflects a variety of in vivo functions. The topological localization
      of the incorporation of nascent peptidoglycan into the cell wall has revealed
      that bacteria have at least two peptidoglycan-synthesizing systems: one for
      septation, the other one for elongation or cell wall thickening. Owing to its
      location on the outside of the cytoplasmic membrane and its specificity, the
      transglycosylation step is an interesting target for antibacterials.
      Glycopeptides and moenomycins are the best studied antibiotics known to interfere
      with this step. Their mode of action and structure-activity relationships have
      been extensively studied. Attempts to synthesize other specific
      transglycosylation inhibitors have recently been made.

PMID- 11320056
TI  - Characterization of sialyltransferase mutants using surface plasmon resonance.
AB  - Sialyltransferases are enzymes responsible for the important sialylation of
      glycoconjugates. Since crystal structures are not available, other tools are
      needed to study enzymatic mechanisms. As a model, we used human alpha2,6
      sialyltransferase. A putative acceptor-binding domain containing the small and
      the very small sialyl motifs was randomly mutated. This resulted in enzymes with
      altered enzymatic activity. Affinity chromatography demonstrated that their
      binding to donor substrate was maintained. To illustrate the role of the mutated
      domain in acceptor binding, a method based on surface plasmon resonance was set
      up. Only at low salt and high acceptor concentration was association of wild-type
      ST6GalI with asialofetuin demonstrated. As expected, this interaction was
      affected by cytidine 5'-monophospho-N-acetylneuraminic acid, the donor substrate,
      which proves the specificity of the interaction. Different types of mutants were
      found. For some, the drop in activity could be explained by loss in affinity for
      the acceptor. For others, the catalytic center, but not the acceptor-binding
      site, was affected. Neither acceptor binding nor catalytic activity were limited
      to the sialyl motifs. To our knowledge, this is the first example in which
      surface plasmon resonance is successfully used to demonstrate the binding of a
      glycosyltransferase to its natural acceptor.

PMID- 11320057
TI  - Anticoagulant heparan sulfate proteoglycans expression in the rat ovary peaks in
      preovulatory granulosa cells.
AB  - Ovarian granulosa cells synthesize anticoagulant heparan sulfate proteoglycans
      (aHSPGs), which bind and activate antithrombin III. To determine if aHSPGs could
      contribute to the control of proteolytic activities involved in follicular
      development and ovulation, we studied the pattern of expression of these
      proteoglycans during the ovarian cycle. aHSPGs were localized on cells and
      tissues by (125)I-labeled antithrombin III binding followed by microscopic
      autoradiography. Localization of aHSPGs has shown that cultured granulosa cells,
      hormonally stimulated by gonadotropins to differentiate in vitro, up-regulate
      their synthesis and release of aHSPGS: In vivo, during gonadotropin-stimulated
      cycle, aHSPGs are present on granulosa cells of antral follicles and are strongly
      labeled in preovulatory follicles. These data demonstrate that aHSPG expression
      in the ovarian follicle is hormonally induced to culminate in preovulatory
      follicles. Moreover, we have shown that five heparan sulfate core proteins mRNA
      (perlecan; syndecan-1, -2, and -4; and glypican-1) are synthesized by granulosa
      cells, providing attachment for anticoagulant heparan sulfate chains on the cell
      surface and in the extracellular matrix. These core proteins are constantly
      expressed during the cycle, indicating that modulations of aHSPG levels observed
      in the ovary are likely controlled at the level of the biosynthesis of
      anticoagulant heparan sulfate glycosaminoglycan chains. This expression pattern
      enables aHSPGs to focus serine protease inhibitors in the developing follicle to
      control proteolysis and fibrin formation at ovulation.

PMID- 11320058
TI  - N-linked oligosaccharides of cobra venom factor contain novel alpha(1
      3)galactosylated Le(x) structures.
AB  - Cobra venom factor (CVF), a nontoxic, complement-activating glycoprotein in cobra
      venom, is a functional analog of mammalian complement component C3b. The
      carbohydrate moiety of CVF consists exclusively of N-linked oligosaccharides with
      terminal alpha1-3-linked galactosyl residues, which are antigenic in human. CVF
      has potential for several medical applications, including targeted cell killing
      and complement depletion. Here, we report a detailed structural analysis of the
      oligosaccharides of CVF. The structures of the oligosaccharides were determined
      by lectin affinity chromatography, antibody affinity blotting, compositional and
      methylation analyses, and high-resolution (1)H-NMR spectroscopy. Approximately
      80% of the oligosaccharides are diantennary complex-type, approximately 12% are
      tri- and tetra-antennary complex-type, and approximately 8% are oligomannose type
      structures. The majority of the complex-type oligosaccharides terminate in
      Galalpha1-3Galbeta1-4(Fucalpha1-3)GlcNAcbeta1, a unique carbohydrate structural
      feature abundantly present in the glycoproteins of cobra venom.

PMID- 11320059
TI  - Human alpha3-fucosyltransferases convert chitin oligosaccharides to products
      containing a GlcNAcbeta1-4(Fucalpha1-3)GlcNAcbeta1-4R determinant at the
      nonreducing terminus.
AB  - Human alpha3-fucosyltransferases (Fuc-Ts) are known to convert N
      acetyllactosamine to Galbeta1-4(Fucalpha1-3)GlcNAc (Lewis x antigen); some of
      them transfer fucose also to GalNAcbeta1-4GlcNAc, generating GalNAcbeta1
      4(Fucalpha1-3)GlcNAc determinants. Here, we report that recombinant forms of Fuc
      TV and Fuc-TVI as well as Fuc-Ts of human milk converted chitin oligosaccharides
      of 2-4 GlcNAc units efficiently to products containing a GlcNAcbeta1-4(Fucalpha1
      3)GlcNAcbeta1-4R determinant at the nonreducing terminus. The product structures
      were identified by mass spectrometry and nuclear magnetic resonance experiments;
      rotating frame nuclear Overhauser spectroscopy data suggested that the fucose and
      the distal N-acetylglucosamine are stacked in the same way as the fucose and the
      distal galactose of the Lewis x determinant. The products closely resembled a
      nodulation factor of Mesorhizobium loti but were distinct from nodulation signals
      generated by NodZ-enzyme.

PMID- 11320060
TI  - The DXD motif is required for GM2 synthase activity but is not critical for
      nucleotide binding.
AB  - We tested the importance of the aspartate-any residue-aspartate (DXD) motif for
      the enzymatic activity and nucleotide binding capacity of the Golgi
      glycosyltransferase GM2 synthase. We prepared point mutations of the motif, which
      is found in the sequence 352-VLWVDDDFV, and analyzed cells that stably expressed
      the mutated proteins. Whereas the folding of the mutated proteins was not
      seriously disrupted as judged by assembly into homodimers, Golgi localization,
      and secretion of a soluble form of the enzyme, exchange of the highly conserved
      aspartic acid residues at position 356 or 358 with alanine or asparagine reduced
      enzyme activity to background levels. In contrast, the D356E and D357N mutations
      retained weak activity, while the activity of V352A and W354A mutants was 167%
      and 24% that of wild-type enzyme, respectively. Despite the major effect of the
      DXD motif on enzymatic activity, nucleotide binding was not altered in the triple
      mutant D356N/D357N/D358N as revealed by binding to UDP-beads and labeling with
      the photoaffinity reagent, P(3)-(4-azidoanilido)uridine 5'-triphosphate (AAUTP).
      In summary, rather than being critical for nucleotide binding, this motif may
      function during catalysis in GM2 synthase, as has been proposed elsewhere for the
      SpsA glycosyltransferase based on its crystal structure.

PMID- 11320061
TI  - Polysialyltransferase ST8Sia II (STX) polysialylates all of the major isoforms of
      NCAM and facilitates neurite outgrowth.
AB  - The neural cell adhesion molecule (NCAM) has different isoforms due to different
      sizes in its polypeptide and plays a significant role in neural development. In
      neural development, the function of NCAM is modified by polysialylation catalyzed
      by two polysialyltransferases, ST8Sia II and ST8Sia IV. Previously, it was
      reported by others that ST8Sia II polysialylates only transmembrane isoforms of
      the NCAM, such as NCAM-140 and NCAM-180, but not NCAM-120 and NCAM-125 anchored
      by a glycosylphosphotidylinositol. In the present study, we first discovered that
      ST8Sia II polysialylates all isoforms of the NCAM examined, and we demonstrated
      that polysialylation of NCAM expressed on 3T3 cells facilitates neurite outgrowth
      regardless of isoforms of NCAM, where polysialic acid is attached. We then show
      that neurite outgrowth is significantly facilitated only when polysialylated NCAM
      is present in cell membranes. Moreover, the soluble NCAM coated on plates did not
      have an effect on neurite outgrowth exerted by soluble L1 adhesion molecule
      coated on plates. These results, taken together, indicate that ST8Sia II plays
      critical roles in modulating the function of all major isoforms of NCAM. The
      results also support previous studies showing that a signal cascade initiated by
      NCAM differs from that initiated by L1 molecule.

PMID- 11320062
TI  - Genomic structure and transcriptional regulation of human Galbeta1,3GalNAc
      alpha2,3-sialyltransferase (hST3Gal I) gene.
AB  - Previous studies have shown that hST3Gal I mRNA is overexpressed in colorectal
      cancer tissues and primary breast carcinoma compared with nonmalignant or benign
      tissue, suggesting that the transcriptional regulation of hST3Gal I gene is
      altered during malignant transformation. We report transcriptional regulation of
      the hST3Gal I gene in colon adenocarcinoma and leukemia cell lines. To determine
      the genomic structure of the 5'-untranslated region, we cloned and identified the
      5'-untranslated region of hST3Gal I from a human genome library. The 5'
      untranslated region was found to be divided into three exons, namely, exons Y, X,
      and C1. The transcription initiation sites map at -1035 bp from the translation
      initiation site. Our results indicate that the transcriptional regulation of
      hST3Gal I depends on the pI promoter that exists 5'-upstream of exon Y in these
      cell lines. The results of luciferase assay suggest that the nt -304 to -145
      region is important for transcriptional activity of hST3Gal I gene in both cell
      lines. The nt -304 to -145 region contains two sequences similar to the Sp1
      recognition elements (GC-box) and one USF binding site. The results of site
      directed mutagenesis indicated that the Sp1 binding sites and USF binding site of
      the pI promoter are involved in the transcription of hST3Gal I mRNA. However, the
      triple mutant of these sites still exhibits about 50% transcriptional activity,
      suggesting that there are other transcription factors involved in the
      transcription of hST3Gal I mRNA. These results suggest that these factors may
      play a critical role in the up-regulation of the hST3Gal I gene during malignant
      transformation.

PMID- 11320063
TI  - Fucosyltransferases in Schistosoma mansoni development.
AB  - Glycoconjugate-bound fucose, abundant in the parasite Schistosoma mansoni, has
      been found in the form of Fucalpha1,3GlcNAc, Fucalpha1,2Fuc, Fucalpha1,6GlcNAc,
      and perhaps Fucalpha1,4GlcNAc linkages. Here we quantify fucosyltransferase
      activities in three developmental stages of S. mansoni. Assays were performed
      using fluorophore-assisted carbohydrate electrophoresis with detection of
      radioactive fucose incorporation from GDP-[(14)C]-fucose into structurally
      defined acceptors. The total fucosyltransferase-specific activity in egg extracts
      was 50-fold higher than that in the other life stages tested (cercaria and adult
      worms). A fucosyltransferase was detected that transferred fucose to type-2
      oligosaccharides (Galbeta1,4GlcNAc-R), both sialylated (with the sialic acid
      attached to the terminal Gal by alpha2,3 or 2,6 linkage) and nonsialylated.
      Another fucosyltransferase was identified that transferred fucose to lactose
      based and type-2 fucosylated oligosaccharides, such as LNFIII
      (Galbeta1,4(Fucalpha1,3)GlcNAcbeta1,3Galbeta1,4Glc). A low level of
      fucosyltransferase that transfers fucose to no-sialylated type-1 oligosaccharides
      (Galbeta1,3GlcNAc-R) was also detected. These studies revealed multifucosylated
      products of the reactions. In addition, the effects of fucose-type iminosugars
      inhibitors were tested on schistosome fucosyltransferases. A new fucose-type 1-N
      iminosugar was four- to sixfold more potent as an inhibitor of schistosome
      fucosyltransferases in vitro than was deoxyfuconojirimycin. In vivo, this novel 1
      iminosugar blocked the expression of a fucosylated epitope (mAb 128C3/3 antigen)
      that is associated with the pathogenesis of schistosomiasis.

PMID- 11320064
TI  - An informatics infrastructure is essential for evidence-based practice.
AB  - The contention of the author is that an informatics infrastructure is essential
      for evidenced-based practice. Five building blocks of an informatics
      infrastructure for evidence-based practice are proposed: 1) standardized
      terminologies and structures, 2) digital sources of evidence, 3) standards that
      facilitate health care data exchange among heterogeneous systems, 4) informatics
      processes that support the acquisition and application of evidence to a specific
      clinical situation, and 5) informatics competencies. Selected examples illustrate
      how each of these building blocks supports the application of evidence to
      practice and the building of evidence from practice. Although a number of major
      challenges remain, medical informatics can provide solutions that have the
      potential to decrease unintended variation in practice and health care errors.

PMID- 11320066
TI  - Structural validation of nursing terminologies.
AB  - OBJECTIVE: The purpose of the study is twofold: 1) to explore the applicability
      of combinatorial terminologies as the basis for building enumerated
      classifications, and 2) to investigate the usefulness of formal terminological
      systems for performing such classification and for assisting in the refinement of
      both combinatorial terminologies and enumerated classifications. DESIGN: A formal
      model of the beta version of the International Classification for Nursing
      Practice (ICNP) was constructed in the compositional terminological language
      GRAIL (GALEN Representation and Integration Language). Terms drawn from the North
      American Nursing Diagnosis Association Taxonomy I (NANDA taxonomy) were mapped
      into the model and classified automatically using GALEN technology. MEASUREMENTS:
      The resulting generated hierarchy was compared with the NANDA taxonomy to assess
      coverage and accuracy of classification. RESULTS: In terms of coverage, in this
      study ICNP was able to capture 77 percent of NANDA terms using concepts drawn
      from five of its eight axes. Three axes-Body Site, Topology, and Frequency-were
      not needed. In terms of accuracy, where hierarchic relationships existed in the
      generated hierarchy or the NANDA taxonomy, or both, 6 were identical, 19 existed
      in the generated hierarchy alone (2 of these were considered suitable for
      incorporation into the NANDA taxonomy and 17 were considered inaccurate), and 23
      appeared in the NANDA taxonomy alone (8 of these were considered suitable for
      incorporation into ICNP, 9 were considered inaccurate, and 6 reflected different,
      equally valid perspectives). Sixty terms appeared at the top level, with no
      indenting, in both the generated hierarchy and the NANDA taxonomy. CONCLUSIONS:
      With appropriate refinement, combinatorial terminologies such as ICNP have the
      potential to provide a useful foundation for representing enumerated
      classifications such as NANDA. Technologies such as GALEN make possible the
      process of building automatically enumerated classifications while providing a
      useful means of validating and refining both combinatorial terminologies and
      enumerated classifications.

PMID- 11320065
TI  - Collaborative efforts for representing nursing concepts in computer-based
      systems: international perspectives.
AB  - Current nursing terminology efforts have converged toward meeting the demand for
      a reference terminology for nursing concepts by building on the foundation of
      existing interface and administrative terminologies and by collaborating with
      terminology efforts across the spectrum of health care. In this article, the
      authors illustrate how collaboration is promoting convergence toward a reference
      terminology for nursing by briefly summarizing a wide range of exemplary
      activities. These include: 1) the International Classification of Nursing
      Practice (ICNP) activities of the International Council of Nurses (ICN), 2) work
      in Brazil and Korea that has contributed to, and been stimulated by, ICNP
      developments, 3) efforts in the United States to improve understanding of the
      different types of terminologies needed in nursing and to promote harmonization
      and linking among them, and 4) current nursing participation in major multi
      disciplinary standards initiatives. Although early nursing terminology work
      occurred primarily in isolation and resulted in some duplicative efforts, the
      activities summarized in this article demonstrate a tremendous level of
      collaboration and convergence not only in the discipline of nursing but in multi
      disciplinary standards initiatives. These efforts are an important prerequisite
      for ensuring that nursing concepts are represented in computer-based systems in a
      manner that facilitates multi-purpose use at local, national, regional, and
      international levels.

PMID- 11320067
TI  - How the past teaches the future: ACMI distinguished lecture.
AB  - More than 30 years of experience in developing a computer-based patient record
      system, The Medical Record (TMR), in multiple settings, in multiple specialty
      groups, and at multiple sites has taught us many lessons. Lessons related to
      computer-based patient records include the importance of a data model in which
      input, storage, and planned use are independent; separation of patient-specific
      data from metadata; a modular design to localize the program code that deals with
      a set of data; redundant storage to optimize tasks and response time; and
      integration of decision support into work process. Lessons related to medical
      informatics include the importance of a clinical-technical partnership, control
      of tools at the leading edge, and rapid prototyping in the real world. Finally,
      changes in technology move the challenges but do not eliminate them.

PMID- 11320068
TI  - Toward an informatics research agenda: key people and organizational issues.
AB  - As we have advanced in medical informatics and created many impressive
      innovations, we also have learned that technologic developments are not
      sufficient to bring the value of computer and information technologies to health
      care systems. This paper proposes a model for improving how we develop and deploy
      information technology. The authors focus on trends in people, organizational,
      and social issues (POI/OSI), which are becoming more complex as both health care
      institutions and information technologies are changing rapidly. They outline key
      issues and suggest high-priority research areas. One dimension of the model
      concerns different organizational levels at which informatics applications are
      used. The other dimension draws on social science disciplines for their
      approaches to studying implications of POI/OSI in informatics. By drawing on a
      wide variety of research approaches and asking questions based in social science
      disciplines, the authors propose a research agenda for high-priority issues, so
      that the challenges they see ahead for informatics may be met better.

PMID- 11320069
TI  - Problem-oriented prefetching for an integrated clinical imaging workstation.
AB  - Prefetching methods have traditionally been used to restore archived images from
      picture archiving and communication systems to diagnostic imaging workstations
      prior to anticipated need, facilitating timely comparison of historical studies
      and patient management. The authors describe a problem-oriented prefetching
      scheme, detailing 1) a mechanism supporting selection of patients for prefetching
      via characterizations of clinical problems, using multiple data sources (picture
      archiving and communication systems, hospital information systems, and radiology
      information systems), classifying patients into cohorts on the basis of their
      medical conditions (e.g., lung cancer); and 2) prefetching of multimedia data
      (imaging, laboratory, and medical reports) from clinical databases to enable the
      viewing of an integrated patient record. Preliminary evaluation of the
      prefetching algorithm using classic information retrieval measures showed that
      the system had high recall (100 percent), correctly identifying and retrieving
      data for all patients belonging to a target cohort, but low precision (50
      percent). A key finding during testing was that the recall of the system was
      increased through the use of multiple data sources (compared with one data
      source), because of better patient descriptors. Medical problems and patient
      cohorts were more specifically defined by combining information from
      heterogeneous databases.

PMID- 11320070
TI  - Using computerized data to identify adverse drug events in outpatients.
AB  - OBJECTIVE: To evaluate the use of a computer program to identify adverse drug
      events (ADEs) in the ambulatory setting and to evaluate the relative contribution
      of four computer search methods for identifying ADEs, including diagnosis codes,
      allergy rules, computer event monitoring rules, and text searching. DESIGN:
      Retrospective analysis of one year of data from an electronic medical record,
      including records for 23,064 patients with a primary care physician, of whom
      15,665 actually came for care. MEASUREMENT: Presence of an ADE; sensitivity and
      specificity of computer searches for ADE. RESULTS: The computer program
      identified 25,056 incidents, which were associated with an estimated 864 (95
      percent confidence interval [CI], 750-978) ADES. Thus, the ADE rate was 5.5 (CI,
      5.2-5.9) per 100 patients coming for care. Furthermore, in 79 (CI, 68-89) ADEs,
      the patient required hospitalization, resulting in an estimated rate of 3.4 (CI,
      2.7-4.3) admissions per 1,000 patients. The sensitivity of the search methods for
      identifying ADEs was estimated to be 58 (CI, 18-98) percent, and the estimated
      specificity was 88 (CI, 87-88) percent. The positive predictive value was 7.5
      (CI, 6.5-8.5) percent, and the negative predictive value was 99.2 (CI, 95.5
      99.98) percent. Compared with age and gender-matched controls with no positive
      screen, patients with ADEs had twice as many outpatient visits and were taking
      nearly three times as many drugs. Antihypertensives, ACE-inhibitors, antibiotics,
      and diuretics were associated with 56 (CI, 47-65) percent of ADES. Among ADEs, 23
      (CI, 16-32) percent were life-threatening or serious, and 38 (CI, 29-47) percent
      were judged preventable. CONCLUSION: Computerized search programs can detect
      ADEs, and free-text searches were especially useful. Adverse drug events were
      frequent, and admissions were not rare, although most hospitals today do not
      identify them. Thus, such detection programs demonstrate "value-added" for the
      electronic record and may be useful for directing and assessing the impact of
      quality improvement efforts.

PMID- 11320071
TI  - Generation and evaluation of intraoperative inferences for automated health care
      briefings on patient status after bypass surgery.
AB  - OBJECTIVE: The authors present a system that scans electronic records from
      cardiac surgery and uses inference rules to identify and classify abnormal events
      (e.g., hypertension) that may occur during critical surgical points (e.g., start
      of bypass). This vital information is used as the content of automatically
      generated briefings designed by MAGIC, a multimedia system that they are
      developing to brief intensive care unit clinicians on patient status after
      cardiac surgery. By recognizing patterns in the patient record, inferences
      concisely summarize detailed patient data. DESIGN: The authors present the
      development of inference rules that identify important information about patient
      status and describe their implementation and an experiment they carried out to
      validate their correctness. The data for a set of 24 patients were analyzed
      independently by the system and by 46 physicians. MEASUREMENTS: The authors
      measured accuracy, specificity, and sensitivity by comparing system inferences
      against physician judgments, in cases where all three physicians agreed and
      against the majority opinion in all cases. RESULTS: For laboratory inferences,
      evaluation shows that the system has an average accuracy of 98 percent (full
      agreement) and 96 percent (majority model). An analysis of interrater agreement,
      however, showed that physicians do not agree on abnormal hemodynamic events and
      could not serve as a gold standard for evaluating hemodynamic events. Analysis of
      discrepancies reveals possibilities for system improvement and causes of
      physician disagreement. CONCLUSIONS: This evaluation shows that the laboratory
      inferences of the system have high accuracy. The lack of agreement among
      physicians highlights the need for an objective quality-assurance tool for
      hemodynamic inferences. The system provides such a tool by implementing
      inferencing procedures established in the literature.

PMID- 11320072
TI  - Record linkage of health care insurance claims.
AB  - OBJECTIVE: This paper provides a detailed description of a method developed for
      purposes of linking records of individual patients, represented in diverse data
      sets, across time and geography. DESIGN: The procedure for record linkage has
      three major components-data standardization, weight estimation, and matching. The
      proposed method was designed to incorporate a combination of exact and
      probabilistic matching techniques. MEASUREMENTS: The procedure was validated
      using convergent, divergent, and criterion validity measures. RESULTS: The output
      of the process achieved a sensitivity of 92 percent and a specificity that
      approached 100 percent. CONCLUSIONS: The procedure is a first step in addressing
      the current trend toward larger and more complex databases.

PMID- 11320073
TI  - Evidence-based nursing practice: a call to action for nursing informatics.

PMID- 11320074
TI  - Presentation of the Morris F. Collen award to Jean-Raoul Scherrer, MD.

PMID- 11320077
TI  - Functionally different agonists induce distinct conformations in the G protein
      coupling domain of the beta 2 adrenergic receptor.
AB  - G protein-coupled receptors represent the largest class of drug discovery
      targets. Drugs that activate G protein-coupled receptors are classified as either
      agonists or partial agonists. To study the mechanism whereby these different
      classes of activating ligands modulate receptor function, we directly monitored
      ligand-induced conformational changes in the G protein-coupling domain of the
      beta(2) adrenergic receptor. Fluorescence lifetime analysis of a reporter
      fluorophore covalently attached to this domain revealed that, in the absence of
      ligands, this domain oscillates around a single detectable conformation. Binding
      to an antagonist does not change this conformation but does reduce the
      flexibility of the domain. However, when the beta(2) adrenergic receptor is bound
      to a full agonist, the G protein coupling domain exists in two distinct
      conformations. Moreover, the conformations induced by a full agonist can be
      distinguished from those induced by partial agonists. These results provide new
      insight into the structural consequence of antagonist binding and the basis of
      agonism and partial agonism.

PMID- 11320076
TI  - Non-small cell lung cancer cyclooxygenase-2-dependent invasion is mediated by
      CD44.
AB  - Elevated tumor cyclooxygenase (COX-2) expression is associated with increased
      angiogenesis, tumor invasion, and suppression of host immunity. We have
      previously shown that genetic inhibition of tumor COX-2 expression reverses the
      immunosuppression induced by non-small cell lung cancer (NSCLC). To assess the
      impact of COX-2 expression in lung cancer invasiveness, NSCLC cell lines were
      transduced with a retroviral vector expressing the human COX-2 cDNA in the sense
      (COX-2-S) and antisense (COX-2-AS) orientations. COX-2-S clones expressed
      significantly more COX-2 protein, produced 10-fold more prostaglandin E(2), and
      demonstrated an enhanced invasive capacity compared with control vector
      transduced or parental cells. CD44, the cell surface receptor for hyaluronate,
      was overexpressed in COX-2-S cells, and specific blockade of CD44 significantly
      decreased tumor cell invasion. In contrast, COX-2-AS clones had a very limited
      capacity for invasion and showed diminished expression of CD44. These findings
      suggest that a COX-2-mediated, CD44-dependent pathway is operative in NSCLC
      invasion. Because tumor COX-2 expression appears to have a multifaceted role in
      conferring the malignant phenotype, COX-2 may be an important target for gene or
      pharmacologic therapy in NSCLC.

PMID- 11320078
TI  - Protein phosphatase 2A activates the HIV-2 promoter through enhancer elements
      that include the pets site.
AB  - Human immunodeficiency virus type 2 (HIV-2) gene expression is regulated by
      upstream promoter elements, including the peri-Ets (pets) site, which mediate
      enhancer stimulation following treatment with the phorbol ester 12-O
      tetradecanoylphorbol-13-acetate (TPA). We previously showed that the oncoprotein
      DEK binds to the pets site in a site-specific manner. In this report, we show
      that binding to the HIV-2 pets site is modulated by treatment of U937 monocytic
      cells with TPA, an activator of protein kinase C. TPA treatment resulted in a
      reduction in the levels of DEK and the formation of a faster migrating pets
      complex in gel shift assays. We show further that the actions of TPA on pets
      binding can be duplicated by phosphatase treatment of nuclear proteins and is
      blocked with okadaic acid, a protein phospatase-2A (PP2A) inhibitor. Finally, we
      demonstrate that ectopic expression of the catalytic domain of PP2A can activate
      the HIV-2 enhancer/promoter alone or in synergy with TPA, an effect mediated in
      part through the pets site. These results suggest that, through an interaction
      with the protein kinase C pathway, PP2A is strongly involved in regulating HIV-2
      enhancer-mediated transcription. This is a consequence of its effects on DEK
      expression and binding to the pets site, as well as its effects on other promoter
      elements. These findings have implications not only for HIV-2 transcription but
      also for multiple cellular processes involving DEK or PP2A.

PMID- 11320079
TI  - On the role of conserved histidine 106 in 10-formyltetrahydrofolate dehydrogenase
      catalysis: connection between hydrolase and dehydrogenase mechanisms.
AB  - The enzyme, 10-formyltetrahydrofolate dehydrogenase (FDH), converts 10
      formyltetrahydrofolate (10-formyl-THF) to tetrahydrofolate in an NADP(+)
      dependent dehydrogenase reaction or an NADP(+)-independent hydrolase reaction.
      The hydrolase reaction occurs in a 310-amino acid long amino-terminal domain of
      FDH (N(t)-FDH), whereas the dehydrogenase reaction requires the full-length
      enzyme. The amino-terminal domain of FDH shares some sequence identity with
      several other enzymes utilizing 10-formyl-THF as a substrate. These enzymes have
      two strictly conserved residues, aspartate and histidine, in the putative
      catalytic center. We have shown recently that the conserved aspartate is involved
      in FDH catalysis. In the present work we studied the role of the conserved
      histidine, His(106), in FDH function. Site-directed mutagenesis experiments
      showed that replacement of the histidine with alanine, asparagine, aspartate,
      glutamate, glutamine, or arginine in N(t)-FDH resulted in expression of insoluble
      proteins. Replacement of the histidine with another positively charged residue,
      lysine, produced a soluble mutant with no hydrolase activity. The insoluble
      mutants refolded from inclusion bodies adopted a conformation inherent to the
      wild-type N(t)-FDH, but they did not exhibit any hydrolase activity. Substitution
      of alanine for three non-conserved histidines located close to the conserved one
      did not reveal any significant changes in the hydrolase activity of N(t)-FDH.
      Expressed full-length FDH with the substitution of lysine for the His(106)
      completely lost both the hydrolase and dehydrogenase activities. Thus, our study
      showed that His(106), besides being an important structural residue, is also
      directly involved in both the hydrolase and dehydrogenase mechanisms of FDH.
      Modeling of the putative hydrolase catalytic center/folate-binding site suggested
      that the catalytic residues, aspartate and histidine, are unlikely to be adjacent
      to the catalytic cysteine in the aldehyde dehydrogenase catalytic center. We
      hypothesize that 10-formyl-THF dehydrogenase reaction is not an independent
      reaction but is a combination of hydrolase and aldehyde dehydrogenase reactions.

PMID- 11320080
TI  - Neuronal Cdc2-like protein kinase (Cdk5/p25) is associated with protein
      phosphatase 1 and phosphorylates inhibitor-2.
AB  - Protein phosphatase 1 (PP1) is complexed with inhibitor 2 (I-2) in the cytosol.
      In rabbit muscle extract PP1.I-2 is activated upon preincubation with ATP/Mg.
      This activation is caused by phosphorylation of I-2 on Thr(72) by glycogen
      synthase kinase 3 (GSK3). We have found that PP1.I-2 in bovine brain extract is
      also activated upon preincubation with ATP/Mg. However, blocking GSK3 action by
      LiCl inhibited only approximately 29% of PP1 activity and indicated that GSK3 is
      not the sole PP1.I-2 activator in the brain. When bovine brain extract was
      analyzed by gel filtration PP1.I-2 and neuronal Cdc2-like protein kinase (NCLK),
      a heterodimer of Cdk5 and the regulatory p25 subunit, co-eluted as a
      approximately 450-kDa size species. The NCLK from the eluted column fractions
      bound to PP1-specific microcystin-Sepharose and glutathione S-transferase (GST)-I
      2-coated glutathione-agarose beads. Similarly, PP1 from the eluted column
      fractions was pulled down with GST-Cdk5-coated glutathione-agarose beads. In
      vitro, NCLK phosphorylated I-2 on Thr(72) and activated PP1.I-2 in an ATP/Mg
      dependent manner. NCLK bound to PP1 through its Cdk5 subunit and the PP1 binding
      region was localized to Cdk5 residues 28-41. Our data demonstrate that in brain
      extract PP1.I-2 and NCLK are associated within a complex of approximately 450 kDa
      and suggest that NCLK is one of the PP1.I-2-activating kinases in the mammalian
      brain.

PMID- 11320081
TI  - Apolipoprotein A-I promotes the formation of phosphatidylcholine core aldehydes
      that are hydrolyzed by paraoxonase (PON-1) during high density lipoprotein
      oxidation with a peroxynitrite donor.
AB  - High density lipoprotein (HDL) is rich in polyunsaturated phospholipids that are
      sensitive to oxidation. However, the effect of apolipoprotein A-I and paraoxonase
      1 (PON-1) on phosphatidylcholine oxidation products has not been identified. We
      subjected native HDL, trypsinized HDL, and HDL lipid suspensions to oxidation by
      the peroxynitrite donor, 3-morpholinosydnonimine. HDL had a basal level of
      phosphatidylcholine mono- and di-hydroperoxides that increased to a greater
      extent in HDL, compared with either trypsinized HDL or HDL lipid alone.
      Phosphatidylcholine core aldehydes, which were present in small amounts,
      increased 10-fold during oxidation of native HDL, compared with trypsinized HDL
      (p = 0.004), and 4-fold compared with HDL lipid suspensions (p = 0.0021). In
      addition, the content of lysophosphatidylcholine increased 300% during oxidation
      of native HDL, but only 80 and 25%, respectively, during oxidation of trypsinized
      HDL and HDL lipid suspensions. Phosphatidylcholine isoprostanes accumulated in
      comparable amounts during the oxidation of all three preparations. Incubation of
      apolipoprotein A-I with 1-palmitoyl-2-linoleoyl glycerophosphocholine
      proteoliposomes in the presence of 3-morpholinosydnonimine or apoAI with
      phosphatidylcholine hydroperoxides resulted in a significant increase in
      phosphatidylcholine core aldehydes with no formation of lysophosphatidylcholine.
      We propose that apolipoprotein A-I catalyzes a one-electron oxidation of alkoxyl
      radicals. Purified PON-1 hydrolyzed phosphatidylcholine core aldehydes to
      lysophosphatidylcholine. We conclude that, upon HDL oxidation with peroxynitrite,
      apolipoprotein AI increases the formation of phosphatidylcholine core aldehydes
      that are subsequently hydrolyzed by PON1.

PMID- 11320082
TI  - Electron transfer and stability of the cytochrome b6f complex in a small domain
      deletion mutant of cytochrome f.
AB  - The lumen segment of cytochrome f consists of a small and a large domain. The
      role of the small domain in the biogenesis and stability of the cytochrome b(6)f
      complex and electron transfer through the cytochrome b(6)f complex was studied
      with a small domain deletion mutant in Chlamydomonas reinhardtii. The mutant is
      able to grow photoautotrophically but with a slower rate than the wild type
      strain. The heme group is covalently attached to the polypeptide, and the visible
      absorption spectrum of the mutant protein is identical to that of the native
      protein. The kinetics of electron transfer in the mutant were measured by flash
      kinetic spectroscopy. Our results show that the rate for the oxidation of
      cytochrome f was unchanged (t(12) = approximately 100 micros), but the half-time
      for the reduction of cytochrome f is increased (t(12) = 32 ms; for wild type,
      t(12) = 2.1 ms). Cytochrome b(6) reduction was slower than that of the wild type
      by a factor of approximately 2 (t(12) = 8.6 ms; for wild type, t(12) = 4.7 ms);
      the slow phase of the electrochromic band shift also displayed a slower kinetics
      (t(12) = 5.5 ms; for wild type, t(12) = 2.7 ms). The stability of the cytochrome
      b(6)f complex in the mutant was examined by following the kinetics of the
      degradation of the individual subunits after inhibiting protein synthesis in the
      chloroplast. The results indicate that the cytochrome b(6)f complex in the small
      domain deletion mutant is less stable than in the wild type. We conclude that the
      small domain is not essential for the biogenesis of cytochrome f and the
      cytochrome b(6)f complex. However, it does have a role in electron transfer
      through the cytochrome b(6)f complex and contributes to the stability of the
      complex.

PMID- 11320083
TI  - Ultraviolet irradiation blocks cellular responses to transforming growth factor
      beta by down-regulating its type-II receptor and inducing Smad7.
AB  - Transforming growth factor-beta (TGF-beta) is a multi-functional cytokine that
      regulates cell growth and differentiation. Cellular responses to TGF-beta are
      mediated through its cell surface receptor complex, which activates transcription
      factors Smad2 and Smad3. Here we report that UV irradiation of mink lung
      epithelial cells causes near complete inhibition of TGF-beta-induced Smad2/3
      mediated gene expression. UV irradiation inhibited TGF-beta-induced
      phosphorylation of Smad2 and subsequent nuclear translocation and DNA binding of
      Smad2/3. Specific cell surface binding of TGF-beta was substantially reduced
      after UV irradiation. This loss of TGF-beta binding resulted from UV-induced down
      regulation of TGF-beta type II receptor (T beta RII) mRNA and protein. UV
      irradiation significantly inhibited T beta RII promoter reporter constructs,
      indicating that UV reduction of T beta RII expression involved transcriptional
      repression. In contrast to its effects on T beta RII, UV irradiation rapidly
      induced Smad7 mRNA and protein. Smad7 is known to antagonize activation of
      Smad2/3 and thereby block TGF-beta-dependent gene expression. UV irradiation
      stimulated Smad7 promoter reporter constructs, indicating that increased Smad7
      expression resulted, at least in part, from increased transcription.
      Overexpression of Smad7 protein to the level induced by UV irradiation inhibited
      TGF-beta-induced gene expression 30%. Maintaining T beta RII levels by
      overexpression of T beta RII prevented UV inhibition of TGF-beta responsiveness.
      Taken together, these data indicate that UV irradiation blocks cellular
      responsiveness to TGF-beta through two mechanisms that impair TGF-beta receptor
      function. The primary mechanism is down-regulation of T beta RII, and the
      secondary mechanism is induction of Smad7.

PMID- 11320084
TI  - Resolution, detection, and characterization of redox conformers of human HSF1.
AB  - We describe here an experimental protocol for the resolution, detection, and
      quantitation of the reduced and oxidized conformers of human heat shock factor 1
      (hHSF1) and report on the effects in vitro and in vivo of redox-active agents on
      the redox status, structure, and function of hHSF1. We showed that diamide, a
      reagent that promotes disulfide bond formation, caused a loss of
      immunorecognition of the monomeric hHSF1 protein in a standard Western blot
      detection procedure. Modification of the Western blot procedure to include
      dithiothreitol in the equilibration and transfer buffers after gel
      electrophoresis allowed for the detection of a compact, intramolecularly
      disulfide cross-linked oxidized hHSF1 (ox-hHSF1) in the diamide-treated sample.
      The effect of diamide was blocked by pretreatment with N-ethylmaleimide and was
      reversed by dithiothreitol added to the sample prior to gel electrophoresis.
      Incubation with nitrosoglutathione at 42 degrees C also promoted the conversion
      of HSF1 to ox-HSF1; at 25 degrees C, however, nitrosoglutathione was by itself
      without effect but blocked the formation of ox-hHSF1 in the presence of diamide.
      The disulfide cross-linked ox-hHSF1 was monomeric and resistant to the in vitro
      heat-induced trimerization and activation. The possibility that ox-HSF1 may occur
      in oxidatively stressed cells was evaluated. Treatment of HeLa cells with 2 mm l
      buthionine sulfoximine promoted the formation of ox-HSF1 and blocked the heat
      induced activation of HSF DNA binding activity. Our result suggests that hHSF1
      may have integrated redox chemistry of cysteine sulfhydryl into its functional
      responses.

PMID- 11320085
TI  - An invariant threonine is involved in self-catalyzed cleavage of the precursor
      protein for ornithine acetyltransferase.
AB  - In Bacillus stearothermophilus ornithine acetyltransferase is a bifunctional
      enzyme, catalyzing the first and the fifth steps of arginine biosynthesis; it
      follows a ping-pong kinetic mechanism. A single chain precursor protein is
      cleaved between the alanine and threonine residues in a highly conserved ATML
      sequence leading to the formation of alpha and beta subunits that assemble into a
      heterotetrameric 2alpha2beta molecule. The beta subunit has been shown to form an
      acetylated intermediate in the course of the transacetylation reaction. The
      present data show that the precursor protein synthesized in vitro or in vivo
      undergoes a self-catalyzed cleavage involving an invariant threonine (Thr-197).
      Using site-directed mutagenesis T197G, T197S, and T197C derivatives have been
      generated. The T197G substitution abolishes both precursor protein cleavage and
      catalytic activity, whereas T197S and T197C substitutions reduce precursor
      cleavage and catalytic activity in the order Thr-197 (wild type) --> Ser-197 -->
      Cys-197. A mechanism is proposed in which Thr-197 plays a crucial role in the
      autoproteolytic cleavage of ornithine acetyltransferase.

PMID- 11320086
TI  - The breast cancer beta 4 integrin and endothelial human CLCA2 mediate lung
      metastasis.
AB  - Adhesion of blood-borne cancer cells to the endothelium is a critical determinant
      of organ-specific metastasis. Here we show that colonization of the lungs by
      human breast cancer cells is correlated with cell surface expression of the
      alpha(6)beta(4) integrin and adhesion to human CLCA2 (hCLCA2), a Ca(2+)-sensitive
      chloride channel protein that is expressed on the endothelial cell luminal
      surface of pulmonary arteries, arterioles, and venules. Tumor cell adhesion to
      endothelial hCLCA2 is mediated by the beta(4) integrin, establishing for the
      first time a cell-cell adhesion property for this integrin that involves an
      entirely new adhesion partner. This adhesion is augmented by an increased surface
      expression of the alpha(6)beta(4) integrin in breast cancer cells selected in
      vivo for enhanced lung colonization but abolished by the specific cleavage of the
      beta(4) integrin with matrilysin. beta(4) integrin/hCLCA2 adhesion-blocking
      antibodies directed against either of the two interacting adhesion molecules
      inhibit lung colonization, while overexpression of the beta(4) integrin in a
      model murine tumor cell line of modest lung colonization potential significantly
      increases the lung metastatic performance. Our data clearly show that the
      beta(4)/hCLCA2 adhesion is critical for lung metastasis, yet expression of the
      beta(4) integrin in many benign breast tumors shows that this integrin is
      insufficient to bestow metastatic competence on cells that lack invasiveness and
      other established properties of metastatic cells.

PMID- 11320087
TI  - Pituitary adenylate cyclase-activating polypeptide and cyclic adenosine 3',5'
      monophosphate stimulate the promoter activity of the rat gonadotropin-releasing
      hormone receptor gene via a bipartite response element in gonadotrope-derived
      cells.
AB  - Specific type I receptors for pituitary adenylate cyclase-activating polypeptide
      (PACAP) are present in gonadotrope cells of the anterior pituitary gland. By
      transient transfection of mouse gonadotrope-derived alphaT3-1 cells, which are
      direct targets for PACAP and express gonadotropin-releasing hormone receptor
      (GnRH-R), a marker of the gonadotrope lineage, we provide the first evidence that
      PACAP stimulates rat GnRH-R gene promoter activity. The EC(50) of this
      stimulation is compatible with a mediation via activation of the cyclic AMP
      dependent signaling pathway and, consistently, co-transfection of an expression
      vector expressing the protein kinase A inhibitor causes reduction in PACAP as
      well as cholera toxin-stimulated promoter activity. Deletion and mutational
      analyses indicate that PACAP activation necessitates a bipartite response element
      that consists of a first region (-272/-237) termed PACAP response element (PARE)
      I that includes a steroidogenic factor-1 (SF-1)-binding site and a second region
      (-136/-101) referred to as PARE II that contains an imperfect cyclic AMP response
      element. Gel shift experiments indicate the specific binding of the SF-1 and a
      potential SF-1-interacting factor to PARE I while a protein immunologically
      related to the cyclic AMP response element-binding protein interacts with PARE
      II. These findings suggest that PACAP might regulate the GnRH-R gene at the
      transcriptional level, providing novel insights into the regulation of pituitary
      specific genes by hypothalamic hypophysiotropic signals.

PMID- 11320088
TI  - Activation of c-Abl kinase activity and transformation by a chemical inducer of
      dimerization.
AB  - c-Abl is a non-receptor tyrosine kinase that is activated in human leukemias by
      the fusion of Bcr or Tel sequences to the Abl NH(2) terminus. Although Bcr and
      Tel have little in common, both contain oligomerization domains. To determine
      whether oligomerization alone is sufficient to activate c-Abl, we have generated
      and characterized an Abl protein that can be activated selectively with the
      chemical inducer of dimerization, AP1510. Mutant Abl proteins with one (c4F1) or
      two (c4F2) copies of the AP1510 binding motif (FKBP) transformed NIH 3T3 cells in
      a ligand-dependent manner with the c4F2 protein 60-fold more potent than c4F1.
      Both chimeric proteins exhibited ligand-dependent dimerization in vivo,
      suggesting that the increased transformation efficiency of the c4F2 mutant
      reflects more effective dimerization rather than formation of higher order
      oligomers. In the absence of ligand, c4F2-expresssing fibroblasts morphologically
      reverted and arrested in G(1). In Ba/F3 cells, the c4F2 chimera exhibited ligand
      dependent kinase activation, transformation to interleukin 3-independent growth,
      and relocalization of the fusion protein from nucleus to cytoplasm. These results
      demonstrate that dimerization alone is sufficient to activate the Abl kinase and
      provide a method to regulate conditionally c-Abl activity that will be useful for
      studying the normal physiological role of c-Abl and the mechanism of
      transformation and leukemogenesis.

PMID- 11320089
TI  - Bcl-xL blocks transforming growth factor-beta 1-induced apoptosis by inhibiting
      cytochrome c release and not by directly antagonizing Apaf-1-dependent caspase
      activation in prostate epithelial cells.
AB  - The mechanism by which transforming growth factor-beta1 (TGF-beta1) induces
      apoptosis of prostate epithelial cells was studied in the NRP-154 rat prostate
      epithelial cell line. TGF-beta 1 down-regulates expression of Bcl-xL and poly(ADP
      ribosyl)polymerase (PARP), promotes cytochrome c release, up-regulates expression
      of latent caspase-3, and activates caspases 3 and 9. We tested the role of Bcl-xL
      in this cascade by stably overexpressing Bcl-xL to prevent loss by TGF-beta 1.
      Clones overexpressing Bcl-xL are resistant to TGF-beta 1 with respect to
      induction of apoptosis, cytochrome c release, activation of caspases 9 and 3, and
      cleavage of PARP; yet they remain sensitive to TGF-beta 1 by cell cycle arrest,
      induction of both fibronectin and latent caspase-3 expression, and loss of PARP
      expression. We show that Bcl-xL associates with Apaf-1 in NRP-154 cells; but this
      association does not inhibit the activation of caspases 9 and 3 by cytochrome c.
      Together, our data suggest that TGF-beta1 induces apoptosis through loss of Bcl
      xL, leading to cytochrome c release and the subsequent activation of caspases 9
      and 3. Moreover, our data demonstrate that the antiapoptotic effect of Bcl-xL
      occurs by inhibition of mitochondrial cytochrome c release and not through
      antagonizing Apaf-1-dependent processing of caspases 9 and 3.

PMID- 11320090
TI  - Gelatin-binding region of human matrix metalloproteinase-2: solution structure,
      dynamics, and function of the COL-23 two-domain construct.
AB  - Human matrix metalloproteinase-2 (MMP-2) contains an array of three fibronectin
      type II (FII) modules postulated to interact with gelatin (denatured collagen).
      Here, we verify that the NMR solution structure of the third FII repeat (COL-3)
      is similar to that of the second FII repeat (COL-2); characterize its ligand
      binding properties; and derive dynamics properties and relative orientation in
      solution for the two domains of the COL-23 fragment, a construct comprising COL-2
      and COL-3 in tandem, with each domain possessing a putative collagen-binding
      site. Interaction of the synthetic gelatin-like octadecapeptide (Pro-Pro-Gly)(6)
      (PPG6) with COL-3 is weaker than with COL-2. We found that a synthetic peptide
      comprising segment 33-42 (peptide 33-42) from the MMP-2 prodomain interacts with
      COL-3 and, albeit with lower affinity, with COL-2 in a way that mimics PPG6
      binding. COL-3 strongly prefers peptide 33-42 over PPG6, which suggests that
      intramolecular interactions with the prodomain could modulate binding of pro-MMP
      2 to its gelatin substrate. In COL-23, the two modules retain their structural
      individuality and tumble independently. Overall, the NMR data indicate that the
      relative orientation of the modules in COL-23 is not fixed in solution, that the
      modules do not interact with one another, and that COL-23 is rather flexible. The
      binding sites face opposite each other, and their responses to, and normalized
      affinities for, the longer ligand PPG12 are virtually identical to those of the
      individual domains for PPG6, thus precluding co- operativity, although they may
      interact simultaneously with multiple sites of the extracellular matrix.

PMID- 11320091
TI  - The carbonate radical is a site-selective oxidizing agent of guanine in double
      stranded oligonucleotides.
AB  - The carbonate radical anion (CO(3)) is believed to be an important intermediate
      oxidant derived from the oxidation of bicarbonate anions and
      nitrosoperoxocarboxylate anions (formed in the reaction of CO(2) with ONOO(-)) in
      cellular environments. Employing nanosecond laser flash photolysis methods, we
      show that the CO(3) anion can selectively oxidize guanines in the self
      complementary oligonucleotide duplex d(AACGCGAATTCGCGTT) dissolved in air
      equilibrated aqueous buffer solution (pH 7.5). In these time-resolved transient
      absorbance experiments, the CO(3) radicals are generated by one-electron
      oxidation of the bicarbonate anions (HCO(3)(-)) with sulfate radical anions
      (SO(4)) that, in turn, are derived from the photodissociation of persulfate
      anions (S(2)O(8)(2-)) initiated by 308-nm XeCl excimer laser pulse excitation.
      The kinetics of the CO(3) anion and neutral guanine radicals, G(-H)( small middle
      dot), arising from the rapid deprotonation of the guanine radical cation, are
      monitored via their transient absorption spectra (characteristic maxima at 600
      and 315 nm, respectively) on time scales of microseconds to seconds. The
      bimolecular rate constant of oxidation of guanine in this oligonucleotide duplex
      by CO(3) is (1.9 +/- 0.2) x 10(7) m(-1) s(-1). The decay of the CO(3) anions and
      the formation of G(-H)( small middle dot) radicals are correlated with one
      another on the millisecond time scale, whereas the neutral guanine radicals decay
      on time scales of seconds. Alkali-labile guanine lesions are produced and are
      revealed by treatment of the irradiated oligonucleotides in hot piperidine
      solution. The DNA fragments thus formed are identified by a standard
      polyacrylamide gel electrophoresis assay, showing that strand cleavage occurs at
      the guanine sites only. The biological implications of these oxidative processes
      are discussed.

PMID- 11320092
TI  - Caspase-3-mediated cleavage of the NF-kappa B subunit p65 at the NH2 terminus
      potentiates naphthoquinone analog-induced apoptosis.
AB  - The transcription factor nuclear factor kappaB (NF-kappaB) plays a crucial role
      in immune and inflammatory response, and protects cells from apoptosis. In this
      report, we investigate whether the NF-kappaB signaling pathway is blocked during
      apoptosis induced by 2,3-dichloro-5,8-dihydroxy-1,4-naphthoquinone (NA), an
      analog of naphthoquinone. It is observed that NA triggers apoptotic cell death in
      HeLa cells and destroys resistance to apoptosis caused by tumor necrosis factor
      alpha. Data presented in this study establish that p65/RelA, a subunit of NF
      kappaB, is cleaved at Asp(97) by caspase-3 during apoptosis. Caspase-3-cleaved
      p65 loses transcriptional activity and potentiates NA-induced apoptosis, in
      contrast to an uncleavable mutant of p65, which protects the cell from apoptosis.
      Caspase-3, which is responsible for the cleavage of p65, is activated via the
      cytochrome c/caspase-9 signaling pathway rather than Fas/caspase-8 pathway during
      NA-induced apoptosis. Our results suggest that NA induces apoptosis by the
      negative regulation of cell survival through caspase-3-mediated cleavage of p65.

PMID- 11320093
TI  - Brefeldin A block of integrin-dependent mechanosensitive ATP release from Xenopus
      oocytes reveals a novel mechanism of mechanotransduction.
AB  - Many animal cells release ATP into the extracellular medium, and often this
      release is mechanosensitive. However, the mechanisms underlying this release are
      not well understood. Using the luciferin-luciferase bioluminescent assay we
      demonstrate that a Xenopus oocyte releases ATP at a basal rate approximately 0.01
      fmol/s, and gentle mechanical stimulation can increase this to 50 fmol/s.
      Brefeldin A, nocodazole, and progesterone-induced- maturation block basal and
      mechanosensitive ATP release. These treatments share the common feature of
      disrupting the Golgi complex and vesicle trafficking to the cell surface and
      thereby block protein secretion and membrane protein insertion. We propose that
      ATP release occurs when protein transport vesicles enriched in ATP fuse with the
      plasma membrane. Collagenase, integrin-binding peptides, and cytochalasin D also
      block ATP release, indicating that extracellular, membrane and cytoskeletal
      elements are involved in the release process. Elevation of intracellular Ca(2+)
      does not evoke ATP release but potentiates mechanosensitive ATP release. Our
      study indicates a novel mechanism of mechanotransduction that would allow cells
      to regulate membrane trafficking and protein transport/secretion in response to
      mechanical loading.

PMID- 11320094
TI  - Membrane topology of the ATP binding cassette transporter ABCR and its
      relationship to ABC1 and related ABCA transporters: identification of N-linked
      glycosylation sites.
AB  - ABCR is a member of the ABCA subclass of ATP binding cassette transporters that
      is responsible for Stargardt macular disease and implicated in retinal transport
      across photoreceptor disc membranes. It consists of a single polypeptide chain
      arranged in two tandem halves, each having a multi-spanning membrane domain
      followed by a nucleotide binding domain. To delineate between several proposed
      membrane topological models, we have identified the exocytoplasmic
      (extracellular/lumen) N-linked glycosylation sites on ABCR. Using trypsin
      digestion, site-directed mutagenesis, concanavalin A binding, and endoglycosidase
      digestion, we show that ABCR contains eight glycosylation sites. Four sites
      reside in a 600-amino acid exocytoplasmic domain of the N-terminal half between
      the first transmembrane segment H1 and the first multi-spanning membrane domain,
      and four sites are in a 275-amino acid domain of the C half between transmembrane
      segment H7 and the second multi-spanning membrane domain. This leads to a model
      in which each half has a transmembrane segment followed by a large exocytoplasmic
      domain, a multi-spanning membrane domain, and a nucleotide binding domain. Other
      ABCA transporters, including ABC1 linked to Tangier disease, are proposed to have
      a similar membrane topology based on sequence similarity to ABCR. Studies also
      suggest that the N and C halves of ABCR are linked through disulfide bonds.

PMID- 11320095
TI  - Enhancement of transport-dependent decarboxylation of phosphatidylserine by S100B
      protein in permeabilized Chinese hamster ovary cells.
AB  - Phosphatidylethanolamine synthesis through the phosphatidylserine (PtdSer)
      decarboxylation pathway requires PtdSer transport from the endoplasmic reticulum
      or mitochondrial-associated membrane to the mitochondrial inner membrane in
      mammalian cells. The transport-dependent PtdSer decarboxylation in permeabilized
      Chinese hamster ovary (CHO) cells was enhanced by cytosolic factors from bovine
      brain. A cytosolic protein factor exhibiting this enhancing activity was
      purified, and its amino acid sequence was partially determined. The sequence was
      identical to part of the amino acid sequence of an EF-hand type calcium-binding
      protein, S100B. A His(6)-tagged recombinant CHO S100B protein was able to
      remarkably enhance the transport-dependent PtdSer decarboxylation in
      permeabilized CHO cells. Under the standard assay conditions for PtdSer
      decarboxylase, the recombinant S100B protein did not stimulate PtdSer
      decarboxylase activity and exhibited no PtdSer decarboxylase activity. These
      results implicated the S100B protein in the transport of PtdSer to the
      mitochondrial inner membrane.

PMID- 11320096
TI  - Structure of the C-domain of human cardiac troponin C in complex with the Ca2+
      sensitizing drug EMD 57033.
AB  - Ca(2+) binding to cardiac troponin C (cTnC) triggers contraction in heart muscle.
      In heart failure, myofilaments response to Ca(2+) are often altered and compounds
      that sensitize the myofilaments to Ca(2+) possess therapeutic value in this
      syndrome. One of the most potent and selective Ca(2+) sensitizers is the
      thiadiazinone derivative EMD 57033, which increases myocardial contractile
      function both in vivo and in vitro and interacts with cTnC in vitro. We have
      determined the NMR structure of the 1:1 complex between Ca(2+)-saturated C-domain
      of human cTnC (cCTnC) and EMD 57033. Favorable hydrophobic interactions between
      the drug and the protein position EMD 57033 in the hydrophobic cleft of the
      protein. The drug molecule is orientated such that the chiral group of EMD 57033
      fits deep in the hydrophobic pocket and makes several key contacts with the
      protein. This stereospecific interaction explains why the (-)-enantiomer of EMD
      57033 is inactive. Titrations of the cCTnC.EMD 57033 complex with two regions of
      cardiac troponin I (cTnI(34-71) and cTnI(128-147)) reveal that the drug does not
      share a common binding epitope with cTnI(128-147) but is completely displaced by
      cTnI(34-71). These results have important implications for elucidating the
      mechanism of the Ca(2+) sensitizing effect of EMD 57033 in cardiac muscle
      contraction.

PMID- 11320097
TI  - Insertion of mitochondrial DNA-encoded F1F0-ATPase subunit 8 across the
      mitochondrial inner membrane in vitro.
AB  - Cytochrome oxidase subunits I, II, and III, the mitochondrial DNA-encoded
      proteins, are inserted across the inner membrane by the Oxa1p-containing
      translocator in a membrane potential-dependent manner. Oxa1p is also involved in
      the insertion of the cytoplasmically synthesized precursor of Oxa1p itself into
      the inner membrane from the matrix via the conservative sorting pathway. The
      mechanism of insertion of the other mitochondrially synthesized proteins,
      however, is unexplored. The insertion of the mitochondrial DNA-encoded subunit 8
      of F(1)F(0)-ATPase (Su8) across the inner membrane was analyzed in vitro using
      the inverted inner membrane vesicles and the Escherichia coli lysate-synthesized
      substrate. This assay revealed that the N-terminal segment of Su8 inserted across
      the membrane to the intermembrane space and assumed the correct trans-cis
      topology depending on the mitochondrial matrix fraction. This translocation
      reaction was similar to those of Sec-independent, direct insertion pathways of E.
      coli and chloroplast thylakoid membranes. (i) It required neither nucleotide
      triphosphates nor membrane potential, and hydrophobic forces drove the process.
      (ii) It did not require protease-sensitive membrane components facing the matrix
      space. (iii) It could be inserted across liposomes in the correct topology in a
      matrix fraction-dependent manner. Thus, a novel mechanism conserved in bacteria
      and chloroplasts also functions in the insertion of Su8 across the mitochondrial
      inner membrane.

PMID- 11320098
TI  - Characterization of a stellate cell activation-associated protein (STAP) with
      peroxidase activity found in rat hepatic stellate cells.
AB  - A proteome approach for the molecular analysis of the activation of rat stellate
      cell, a liver-specific pericyte, led to the discovery of a novel protein named
      STAP (stellate cell activation-associated protein). We cloned STAP cDNA. STAP is
      a cytoplasmic protein with molecular weight of 21,496 and shows about 40% amino
      acid sequence homology with myoglobin. STAP was dramatically induced in in vivo
      activated stellate cells isolated from fibrotic liver and in stellate cells
      undergoing in vitro activation during primary culture. This induction was seen
      together with that of other activation-associated molecules, such as smooth
      muscle alpha-actin, PDGF receptor-beta, and neural cell adhesion molecule. The
      expression of STAP protein and mRNA was augmented time dependently in
      thioacetamide-induced fibrotic liver. Immunoelectron microscopy and proteome
      analysis detected STAP in stellate cells but not in other hepatic constituent
      cells. Biochemical characterization of recombinant rat STAP revealed that STAP is
      a heme protein exhibiting peroxidase activity toward hydrogen peroxide and
      linoleic acid hydroperoxide. These results indicate that STAP is a novel
      endogenous peroxidase catabolizing hydrogen peroxide and lipid hydroperoxides,
      both of which have been reported to trigger stellate cell activation and
      consequently promote progression of liver fibrosis. STAP could thus play a role
      as an antifibrotic scavenger of peroxides in the liver.

PMID- 11320099
TI  - Specific force deficit in skeletal muscles of old rats is partially explained by
      the existence of denervated muscle fibers.
AB  - We tested the hypothesis that denervated muscle fibers account for part of the
      specific force (sF(o)) deficit observed in muscles from old adult (OA) mammals.
      Whole muscle force (F(o)) was quantified for extensor digitorum longus (EDL)
      muscles of OA and young adult (YA) rats. EDL muscle sF(o) was calculated by
      dividing F(o) by either total muscle fiber cross-sectional area (CSA) or by
      innervated fiber CSA. Innervated fiber CSA was estimated from EDL muscle cross
      sections labeled for neural cell adhesion molecules, whose presence is a marker
      for muscle fiber denervation. EDL muscles from OA rats contained significantly
      more denervated fibers than muscles from YA rats (5.6% vs 1.1% of total CSA).
      When compared with YA muscle, OA muscle demonstrated deficits of 34.1% for F(o),
      28.3% for sF(o), and 24.9% for sF(o) calculated by using innervated CSA as the
      denominator. Denervated muscle fibers accounted for 11.3% of the specific force
      difference between normal YA and OA skeletal muscle. Other mechanisms in addition
      to denervation account for the majority of the sF(o) deficit with aging.

PMID- 11320100
TI  - Kinetics of human aging: I. Rates of senescence between ages 30 and 70 years in
      healthy people.
AB  - A calculation of loss rates is reported for human structural and functional
      variables from a substantially larger data set than has been previously studied.
      Data were collected for healthy, nonsmoking human subjects of both sexes from a
      literature search of cross-sectional, longitudinal, and cross-sequential studies.
      The number of studies analyzed was 469, and the total number of subjects was
      54,274. A linear model provided a fit of the data, for each variable, that was
      not significantly different from the best polynomial fit. Therefore, linear loss
      rates (as a percent decline per year from the reference value at age 30) were
      calculated for 445 variables from 13 organ systems, and additionally for 24
      variables even more integrative, such as maximum oxygen consumption and exercise
      performance, that express effects of multiple contributing variables and systems.
      The frequency distribution of the 13 individual system linear loss rates (as
      percent loss per year) for a very healthy population has roughly a unimodal,
      right-skewed shape, with mean 0.65, median 0.5, and variance 0.32. (The actual
      underlying distribution could be a truncated Gaussian, an exponential, Poisson,
      gamma or some other). The linear estimates of loss rates were clustered between
      0% and 2% per year for variables from most organ systems, with exceptions being
      the endocrine, thermoregulatory, and gastrointestinal systems, for which wider
      ranges (up to approximately 3% per year) of loss rates were found. We suggest
      that this set of linear losses over time, observed in healthy individuals between
      ages (approximately) 30 to 70 years, exposes the underlying kinetics of human
      senescence, independent of effects of substantial disease.

PMID- 11320101
TI  - Longitudinal muscle strength changes in older adults: influence of muscle mass,
      physical activity, and health.
AB  - The longitudinal changes in isokinetic strength of knee and elbow extensors and
      flexors, muscle mass, physical activity, and health were examined in 120 subjects
      initially 46 to 78 years old. Sixty-eight women and 52 men were reexamined after
      9.7 +/- 1.1 years. The rates of decline in isokinetic strength averaged 14% per
      decade for knee extensors and 16% per decade for knee flexors in men and women.
      Women demonstrated slower rates of decline in elbow extensors and flexors (2% per
      decade) than men (12% per decade). Older subjects demonstrated a greater rate of
      decline in strength. In men, longitudinal rates of decline of leg muscle strength
      were approximately 60% greater than estimates from a cross-sectional analysis in
      the same population. The change in leg strength was directly related to the
      change in muscle mass in both men and women, and it was inversely related to the
      change in medication use in men. Physical activity declined yet was not directly
      associated with strength changes. Although muscle mass changes influenced the
      magnitude of the strength changes over time, strength declines in spite of muscle
      mass maintenance or even gain emphasize the need to explore the contribution of
      other cellular, neural, or metabolic mediators of strength changes.

PMID- 11320102
TI  - Effect of age on the gastrointestinal-associated mucosal immune response of
      humans.
AB  - Age-related changes in gastrointestinal-associated mucosal immune response have
      not been well studied. Thus, we investigated the effect of age on this response
      and compared these responses to those of peripheral immune cells. Saliva, blood,
      and intestinal biopsies were collected from young and old healthy subjects to
      determine immunoglobulin (Ig) levels and to isolate peripheral blood mononuclear
      cells, intraepithelial lymphocytes (IELs), and lamina propria lymphocytes (LPLs).
      Although subject age did not influence the level of total IgA found in saliva,
      IgA levels in serum increased (p <.05) with age. Older subjects' peripheral blood
      mononuclear cell proliferation and IL-2 production were significantly lower than
      those of young subjects. LPLs from older subjects produced significantly less IL
      2 in response to all stimuli than did that from the young. IEL's ability to
      proliferate and produce IL-2 was not affected by subject age. Thus, LPL but not
      IEL demonstrated an age-related decline in immune function similar to that seen
      in peripheral lymphocytes.

PMID- 11320103
TI  - Skeletal muscle regeneration in very old rats.
AB  - This study was undertaken to assess the regenerative capacity of skeletal muscle
      in rats near the end of their normal life span. Two experiments were performed.
      In the first, extensor digitorum longus (EDL) muscles were cross-age transplanted
      from 32-month-old male inbred Wistar (WI/HicksCar) rats in place of an EDL muscle
      in 4-month-old hosts. The other EDL muscle in the hosts was autotransplanted.
      After 60 days, the old-into-young muscle transplants regenerated as well as the
      young-into-young autotransplants. In the second experiment, EDL muscles in young
      adult (4 months) and old rats (32 and 34 months) of WI/HicksCar and Brown Norway
      (BN) were injected with a local anesthetic, bupivacaine, and allowed to
      regenerate for 41 days. In all cases, the masses and absolute maximum tetanic
      force of the regenerates equaled or exceeded those of untouched contralateral
      control muscles. These experiments showed that under appropriate conditions, very
      old muscles can regenerate to equal or exceed the contralateral control values,
      which in old rats are much less than those in muscles of young rats.

PMID- 11320104
TI  - Andropause: is it time for the geriatrician to treat it?

PMID- 11320105
TI  - Effects of transdermal testosterone on bone and muscle in older men with low
      bioavailable testosterone levels.
AB  - BACKGROUND: A large proportion of men over 65 years of age have bioavailable
      testosterone levels below the reference range of young adult men. The impact of
      this on musculoskeletal health and the potential for improvement in function in
      this group with testosterone supplementation require investigation. METHODS:
      Sixty-seven men (mean age 76 +/- 4 years, range 65--87) with bioavailable
      testosterone levels below 4.44 nmol/l (lower limit for adult normal range) were
      randomized to receive transdermal testosterone (two 2.5-mg patches per day) or
      placebo patches for 1 year. All men received 500 mg supplemental calcium and 400
      IU vitamin D. Outcome measures included sex hormones (testosterone, bioavailable
      testosterone, sex-hormone binding globulin [SHBG], estradiol, and estrone), bone
      mineral density (BMD; femoral neck, Ward's triangle, trochanter, lumbar spine,
      and total body), bone turnover markers, lower extremity muscle strength, percent
      body fat, lean body mass, hemoglobin, hematocrit, prostate symptoms, and prostate
      specific antigen (PSA) levels. RESULTS: Twenty-three men (34%) withdrew from the
      study; 44 men completed the trial. In these men, bioavailable testosterone levels
      increased from 3.2 +/- 1.2 nmol/l (SD) to 5.6 +/- 3.5 nmol/l (p <.002) at 12
      months in the testosterone group, whereas no change occurred in the control
      group. Although there was no change in estradiol levels in either group, estrone
      levels increased in the testosterone group (103 +/- 26 pmol/l to 117 +/- 33
      pmol/l; p <.017). The testosterone group had a 0.3% gain in femoral neck BMD,
      whereas the control group lost 1.6% over 12 months (p =.015). No significant
      changes were seen in markers of bone turnover in either group. Improvements in
      muscle strength were seen in both groups at 12 months compared with baseline
      scores. Strength increased 38% (p =.017) in the testosterone group and 27% in the
      control group (p =.06), with no statistical difference between the groups. In the
      testosterone group, body fat decreased from 26.3 +/- 5.8% to 24.6 +/- 6.5% (p
      =.001), and lean body mass increased from 56.2 +/- 5.3 kg to 57.2 +/- 5.1 kg (p
      =.001), whereas body mass did not change. Men receiving testosterone had an
      increase in PSA from 2.0 +/- 1.4 microg/l to 2.6 +/- 1.8 microg/l (p =.04),
      whereas men receiving placebo had an increase in PSA from 1.9 +/- 1.0 microg/l to
      2.2 +/- 1.5 microg/l (p =.09). No significant differences between groups were
      seen in hemoglobin, hematocrit, symptoms or signs of benign prostate hyperplasia,
      or PSA levels. CONCLUSIONS: Transdermal testosterone (5 mg/d) prevented bone loss
      at the femoral neck, decreased body fat, and increased lean body mass in a group
      of healthy men over age 65 with low bioavailable testosterone levels. In
      addition, both testosterone and placebo groups demonstrated gains in lower
      extremity muscle strength, possibly due to the beneficial effects of vitamin D.
      Testosterone did result in a modest increase in PSA levels but resulted in no
      change in signs or symptoms of prostate hyperplasia.

PMID- 11320106
TI  - Orthostatic hypotension in elderly persons during passive standing: a comparison
      with young persons.
AB  - BACKGROUND: The present study was aimed at clarifying the mechanism of
      orthostatic hypotension (OH) that occurs in elderly persons and at investigating
      assisting methods to prevent OH by evaluating changes in autonomic nervous system
      (ANS) activity and cerebral circulation of elderly persons when engaged in
      passive standing. METHODS: Eight elderly volunteers and 9 young volunteers gave
      informed consent to participate in the study. Two experimental conditions were
      established: (i) "active standing," in which the subjects stood on their own with
      guidance from an assistant, and (ii) "passive standing," in which the subjects
      were placed in a standing position completely by an assistant. ANS was determined
      before and after standing by measuring the heart rate variability. The reaction
      of the ANS was evaluated on the basis of low-frequency power (LF: 0.05--0.15 Hz)
      and high-frequency power (HF: 0.15--0.4 Hz), which were separated from the R-R
      interval data by power spectral analysis using the fast Fourier transformation.
      Cerebral perfusion was measured over the right frontal region using a near
      infrared spectroscopy cerebral oxygen monitor. RESULTS: The main findings were:
      (i) Transient decreases in blood pressure occurred immediately after standing in
      both the young and elderly subjects. (ii) The LF:HF ratio increased significantly
      ( p <.05) immediately after active standing in the young subjects, whereas this
      ratio increased in the elderly subjects after some delay. (iii) The LF:HF ratio
      increased significantly ( p <.01) immediately after passive standing in the young
      subjects, whereas this ratio decreased significantly ( p <.05) in the elderly
      subjects. (iv) In the elderly subjects, the total hemoglobin (HbT) and
      oxyhemoglobin showed the greatest decrease during the 15-second period after
      standing. The maximum changes in the HbT with passive standing differed
      significantly ( p <.01) from those observed during active standing. CONCLUSIONS:
      Our findings emphasize the need to devise bioengineered means that allow elderly
      persons to exert themselves, to maintain or improve muscle contractility and ANS
      function, while providing minimum assistance for standing.

PMID- 11320107
TI  - Effect of intense strength training on standing balance, walking speed, and sit
      to-stand performance in older adults.
AB  - BACKGROUND: Muscle size and strength decrease with aging, and the resultant
      muscle weakness has been implicated in increased risk of falls in older adults.
      These falls have large economic and functional costs. METHODS: The purpose of
      this randomized, controlled study was to determine if an 8-week, 3-day per week
      intense (77.8 +/- 3.4% of 1-repetition maximum [1RM]) strength training program
      could improve functional ability related to the risk of falling in subjects aged
      61--87 years (mean 72, SD 6.3). Twelve strength-training-naive subjects performed
      two sets of 10 repetitions for six lower body exercises while 12 subjects served
      as nonintervention controls. Subjects were tested pre-, mid-, and
      postintervention for strength gain and on three tests of functional ability.
      RESULTS: Postintervention strength was significantly better (p <.017) in all
      training subjects across all exercises, and no injuries were reported as a result
      of either training or 1RM testing. After controlling for preintervention
      differences, repeated measure analysis of covariance (ANCOVA) found a significant
      difference between experimental and nonintervention control subjects for
      postintervention maximal walking speed [F(1,19) = 5.03, p <.05]. There were no
      significant between-group differences for 1-leg blind balance time or 5
      repetition sit-to-stand performance [F(1,19) =.082; F(1,19) =.068, respectively,
      p >.05]. CONCLUSIONS: These findings suggest that strength training alone does
      not appear to enhance standing balance or sit-to-stand performance in active,
      community-dwelling older adults but that it may improve maximal walking speed.
      The relationship between strength gain and risk of falls remains unclear. The
      data do reinforce the notion that intense strength training is a safe and
      effective way to increase muscle strength in this population.

PMID- 11320108
TI  - Laparoscopic nephrectomy in young-old, old-old, and oldest-old adults.
AB  - BACKGROUND: This study reports findings for laparoscopic nephrectomy in
      comparison with open nephrectomy in geriatric patients. METHODS: Since 1993, a
      total of 249 patients have undergone nephrectomy for benign disease at the
      Medical University of Lubeck, Germany. In 11 patients older than 65 years, a
      laparoscopic nephrectomy was performed (in the majority via a transperitoneal
      approach), and 42 patients older than 65 years underwent an open-flank
      nephrectomy. Clinical parameters were evaluated in comparison with both groups
      and stratified according to age groups. RESULTS: With respect to operative
      results (operative duration and pre- and postoperative hemoglobin levels), no
      relevant differences were observed between the laparoscopy group and the open
      nephrectomy group, even when stratified according to patient age. However,
      patients in the laparoscopy group demonstrated a significant advantage concerning
      blood loss and the number of required blood transfusions, regardless of age. In
      addition, patients after laparoscopy showed advantages in the postoperative
      course. Benefits were proven for the analgesic consumption, hospital stay, and
      convalescence parameters. Although complication rates were comparable in both
      groups, an increase was observed in both groups for patients aged between 75 and
      84 years. CONCLUSIONS: Laparoscopic nephrectomy offers comparable operative
      results (with reduced blood loss and less need for blood transfusions) when
      compared with open surgery. Significant advantages can be demonstrated in the
      postoperative course, and especially geriatric patients benefit from these
      aspects of the minimally invasive approach. Laparoscopy should be regarded as the
      primary therapeutic option for nephrectomy for benign disease in these patients.

PMID- 11320109
TI  - Clinical characteristics and six-month outcomes of nursing home residents with
      low activities of daily living dependency.
AB  - BACKGROUND: Up to 30% of nursing home residents have very little dependency in
      activities of daily living (ADLs). We compared the characteristics and six-month
      outcomes of a sample of low-ADL--dependent nursing home residents (LDR) with
      other residents. METHODS: This is a cross-sectional, six-month follow-up study
      using secondary data analysis. We combined the separate 1990 and 1993 cohorts in
      the Resident Assessment Instrument evaluation study. In each case these data were
      collected in the same 254 nursing homes in 10 states. We studied residents with a
      length of stay greater than 60 days and age 65 years and older (N = 3955). We
      compared the baseline characteristics of LDR (n = 985) with all other residents.
      We then compared six-month outcomes of LDR with other residents and
      characteristics of LDR with poor outcomes (death or worsened ADL disability) with
      LDR who remained stable. RESULTS: The LDR had a significantly decreased frequency
      of geriatric syndromes (i.e., cognitive impairment, urinary incontinence, under
      nutrition, vision problems, poor balance, and pressure ulcers) and neurological
      disease but had the same frequency of non-neurological chronic diseases and were
      on more medications. Thirty-one percent had poor six-month outcomes associated
      with baseline poor cognition, incontinence, poor appetite, and presence of
      vascular disease, daily pain, shortness of breath, and multiple medications.
      CONCLUSION: Our research identified 29% of nursing home residents with higher
      physical function (LDR) who had fewer geriatric syndromes and neurological
      disease diagnoses; 69% of these remained stable at 6 months. Those LDR with a
      higher risk of poor outcomes could be prospectively identified. LDR who remained
      stable for 6 months may represent a group who could potentially be maintained in
      the community.

PMID- 11320110
TI  - Aerobic exercise and resting blood pressure in older adults: a meta-analytic
      review of randomized controlled trials.
AB  - BACKGROUND: It is well established that resting systolic and diastolic blood
      pressure (SBP and DBP, respectively) increases as one ages. This study used the
      meta-analytic approach to examine the effects of aerobic exercise for reducing
      resting SBP and DBP in older adults. METHODS: Study data were compiled through
      use of the following: (i) computer searches (MEDLINE, Current Contents, and Sport
      Discus), (ii) cross-referencing from bibliographies of retrieved studies and
      review articles, and (iii) an expert who reviewed our reference list. Inclusion
      criteria and sources for this study were (i) randomized trials, (ii) aerobic
      activity as the only exercise intervention, (iii) a nonexercise control group,
      (iv) an assessment of changes in resting SBP and/or DBP, (v) within-study ages of
      subjects > or = 50 years, (vi) English-language studies published in journals,
      and (vii) studies published between January 1966 and January 1998. Net changes in
      resting BP were calculated as the exercise minus control group difference.
      RESULTS: Fourteen primary outcomes were derived from seven studies. Decreases of
      approximately 2% and 1% were found for resting SBP and DBP, with only changes in
      SBP as statistically significant (SBP, mean +/- SD = -2 +/- 3 mm Hg, 95%
      confidence interval [CI] = -4 to -1 mm Hg; DBP, mean +/- SD = -1 +/- 2 mm Hg, 95%
      CI = -2 to 0 mm Hg). CONCLUSIONS: This study supports the efficacy of aerobic
      exercise for reducing resting SBP in older adults. However, a need exists for
      studies that address the effectiveness of this intervention for reducing resting
      BP in older adults.

PMID- 11320111
TI  - Geographical structure and host specificity in bacteria and the implications for
      tracing the source of coliform contamination.

PMID- 11320112
TI  - Endotoxic properties of lipid A from Comamonas testosteroni.
AB  - The lipid A from Comamonas testosteroni has been isolated and its complete
      chemical structure determined [Iida, T., Haishima, Y., Tanaka, A., Nishijima, K.,
      Saito, S. & Tanamoto, K. (1996). Eur J Biochem 237, 468-475]. In this work, the
      relationship between its chemical structure and biological activity was studied.
      The lipid A was highly homogeneous chemically and was characterized by the
      relatively short chain length (C(10)) of the 3-hydroxy fatty acid components
      directly bound to the glucosamine disaccharide backbone by either amide or ester
      linkages. The lipid A exhibited endotoxic activity in all of the assay systems
      tested (mitogenicity in mouse spleen cells; induction of tumour necrosis factor
      alpha release from both mouse peritoneal macrophages and mouse macrophage-like
      cell line J774-1, as well as from the human monocytic cell line THP-1; induction
      of nitric oxide release from J774-1 cells; Limulus gelation activity and lethal
      toxicity in galactosamine-sensitized mice) to the same extent as did 'Salmonella
      minnesota' lipid A or Escherichia coli LPS used as controls. The strong endotoxic
      activity of the C. testosteroni lipid A indicates that the composition of 3
      hydroxydecanoic acid is not responsible for the low endotoxicity of the lipid A
      observed in members of the genus Rhodopseudomonas, as has previously been
      suggested. Furthermore, both the lack of a second acylation of the 3-hydroxy
      fatty acid attached at the 3' position, and the substitution of the hydroxyl
      group of the 3-hydroxy fatty acid attached at position 2, do not affect the
      manifestation of endotoxic activity or species specificity.

PMID- 11320113
TI  - Comparative genetic characterization of Listeria monocytogenes isolates from
      human and animal listeriosis cases.
AB  - Listeria monocytogenes isolates from human sporadic and epidemic cases (n=119)
      and from animal cases (n=76) were characterized by automated ribotyping and PCR
      restriction fragment length polymorphism (PCR-RFLP) typing of the virulence genes
      actA and hly. This combination of typing methods differentiated 39 distinctive
      strains, each reflecting a unique combination of ribotypes, hly and actA alleles.
      Simpson's index of discrimination indicated a high discriminatory ability of
      ribotyping for both animal (0.867) and human isolates (0.857), which was further
      increased by the addition of hly and actA typing (0.916 and 0.904, respectively).
      Ribotype and hly allele data were further used to group isolates into three
      genetically distinct lineages. Each lineage is composed of several ribotype
      fragment subsets, each of which contains multiple ribotypes characterized by
      common ribotype fragments. To determine whether certain clones of L.
      monocytogenes show indications for unique pathogenic potential or host
      specificity, frequency distributions for five genetic characteristics (i.e.
      lineage, ribotype, ribotype fragment subset and hly and actA allele) were
      calculated for isolates from animal cases, human epidemic cases and human
      sporadic cases. Lineage III isolates were found less frequently in human cases (1
      of 119 isolates) than in animal cases (8 of 76 isolates; P=0.003). These results
      suggest the possibility of host specificity for non-primate mammals among lineage
      III strains. In addition, lineage I strains were found more frequently among
      human cases than among animal cases (P<0.001). Among the eight hly alleles
      observed, hly allele 1 was more common among human isolates as compared to animal
      isolates (P=0.002). We also identified one ribotype (DUP-1030) which was
      significantly more common among animal isolates (P=0.005) and one ribotype (DUP
      1038; lineage I) which was significantly more common among human epidemic
      isolates as compared to human sporadic isolates (P<0.001). These findings confirm
      the presence of clonal groups of L. monocytogenes, which appear to be
      characterized by unique virulence or host specificity patterns. This study also
      establishes baseline data describing the genetic diversity of human and animal L.
      monocytogenes isolates which can be utilized in future surveillance programmes to
      track the emergence of new strains.

PMID- 11320114
TI  - Pseudomonas aeruginosa mutations in lasI and rhlI quorum sensing systems result
      in milder chronic lung infection.
AB  - To understand the importance of quorum sensing in chronic Pseudomonas aeruginosa
      lung infection, the in vivo pathogenic effects of the wild-type P. aeruginosa
      PAO1 and its double mutant, PAO1 lasI rhlI, in which the signal-generating parts
      of the quorum sensing systems are defective were compared. The rat model of P.
      aeruginosa lung infection was used in the present study. The rats were killed on
      days 3, 7, 14 and 28 after infection with the P. aeruginosa strains. The results
      showed that during the early stages of infection, the PAO1 double mutant induced
      a stronger serum antibody response, higher production of pulmonary interferon
      gamma, and more powerful blood polymorphonuclear leukocyte (PMN)
      chemiluminescence compared to its wild-type counterpart. On days 14 and 28 post
      infection, significantly milder lung pathology, a reduction in the number of mast
      cells present in the lung foci, a reduced number of lung bacteria, and minor
      serum IgG and IgG1 responses but increased lung interferon gamma production were
      detected in the group infected with the PAO1 double mutant when compared with the
      PAO1-infected group. Delayed immune responses were observed in the PAO1-infected
      group and they might be associated with the production of virulence factors that
      are controlled by the quorum sensing systems. The conclusion of this study is
      that functional lasI and rhlI genes of P. aeruginosa PAO1 play a significant role
      during lung infection.

PMID- 11320115
TI  - Functional analysis of yersiniabactin transport genes of Yersinia enterocolitica.
AB  - Yersinia enterocolitica O:8, biogroup (BG) IB, strain WA-C carries a high
      pathogenicity island (HPI) including iron-repressible genes (irp1-9, fyuA) for
      biosynthesis and uptake of the siderophore yersiniabactin (Ybt). The authors
      report the functional analysis of irp6,7,8, which show 98-99% similarity to the
      corresponding genes ybtP,Q,X on the HPI of Yersinia pestis. It was demonstrated
      that irp6,7 are involved in ferric (Fe)-Ybt utilization and mouse virulence of Y.
      enterocolitica, thus confirming corresponding results for Y. pestis. Additionally
      it was shown that inactivation of the ampG-like gene irp8 did not affect either
      Fe-Ybt utilization or mouse virulence. To determine whether irp6, irp7 and fyuA
      (encoding the outer-membrane Fe-Ybt/pesticin receptor FyuA) are sufficient to
      mediate Fe-Ybt transport/utilization, these genes were transferred into
      Escherichia coli entD,F and into non-pathogenic Y. enterocolitica, BG IA, strain
      NF-O. Surprisingly, E. coli entD,F but not Y. enterocolitica NF-O gained the
      capability to utilize exogenous Fe-Ybt as a result of this gene transfer,
      although both strains expressed functional FyuA (pesticin sensitivity). These
      results suggest that besides irp6, irp7 and fyuA, additional genes are required
      for sufficient Fe-Ybt transport/utilization. Finally, it was shown that irp6,
      irp7 and fyuA but not irp8 are involved in controlling Ybt biosynthesis and fyuA
      gene expression: irp6 and/or irp7 mutation leads to upregulation whereas fyuA
      mutation leads to downregulation. However, fyuA-dependent control of Ybt
      biosynthesis could be bypassed in a fyuA mutant by ingredients of chrome azurol S
      (CAS) siderophore indicator agar.

PMID- 11320116
TI  - Functional characterization of a microbial aquaglyceroporin.
AB  - The major intrinsic proteins (MIPs) constitute a widespread membrane channel
      family essential for osmotic cell equilibrium. The MIPs can be classified into
      three functional subgroups: aquaporins, glycerol facilitators and
      aquaglyceroporins. Bacterial MIP genes have been identified in archaea as well as
      in Gram-positive and Gram-negative eubacteria. However, with the exception of
      Escherichia coli, most bacterial MIPs have been analysed by sequence homology.
      Since no MIP has yet been functionally characterized in Gram-positive bacteria,
      we have studied one of these members from Lactococcus lactis. This MIP is shown
      to be permeable to glycerol, like E. coli GlpF, and to water, like E. coli AqpZ.
      This is the first characterization of a microbial MIP that has a mixed function.
      This result provides important insights to reconstruct the evolutionary history
      of the MIP family and to elucidate the molecular pathway of water and other
      solutes in these channels.

PMID- 11320117
TI  - Eubacterial arylamine N-acetyltransferases - identification and comparison of 18
      members of the protein family with conserved active site cysteine, histidine and
      aspartate residues.
AB  - Arylamine N-acetyltransferases (NATs) are enzymes involved in the detoxification
      of a range of arylamine and hydrazine-based xenobiotics. NATs have been
      implicated in the endogenous metabolism of p-aminobenzoyl glutamate in
      eukaryotes, although very little is known about the distribution and function of
      NAT in the prokaryotic kingdom. Using DNA library screening techniques and the
      analysis of data from whole-genome sequencing projects, we have identified 18 nat
      like sequences from the Proteobacteria and Firmicutes. Recently, the three
      dimensional structure of NAT derived from the bacterium Salmonella typhimurium
      (PDB accession code 1E2T) was resolved and revealed an active site catalytic
      triad composed of Cys(69)-His(107)-Asp(122). These residues have been shown to be
      conserved in all prokaryotic and eukaryotic NAT homologues together with three
      highly conserved regions which are found proximal to the active site triad. The
      characterization of prokaryotic NATs and NAT-like enzymes is reported. It is also
      predicted that prokaryotic NATs, based on gene cluster composition and
      distribution amongst genomes, participate in the metabolism of xenobiotics
      derived from decomposition of organic materials.

PMID- 11320118
TI  - Evaluation of in vivo activation of protein kinase A under non-dissociable
      conditions through the overexpression of wild-type and mutant regulatory subunits
      in Saccharomyces cerevisiae.
AB  - BCY1-encoded protein kinase A (PKA) wild-type and mutant regulatory (R) subunits
      from Saccharomyces cerevisiae were inducibly overexpressed in their corresponding
      background strains containing the same mutation in the bcy1 gene. The aim of this
      approach was to shift the catalytic activity of PKA within the cell to the
      undissociated holoenzyme form(s) in order to evaluate whether the wild-type or
      the mutant forms of the holoenzyme could display catalytic activity. Two mutants
      of R subunits were used: bcy1-16, with a complete deletion of cAMP-binding domain
      B; and bcy1-14, with a small deletion in the carboxy terminus of cAMP-binding
      domain A. Their overexpression caused an increase in the level of R subunits in
      the range 40-90-fold, as detected by cAMP-binding activity, Coomasie-stained SDS
      PAGE and Western blot analysis. The change in PKA activity attained by
      overexpression of R was assessed in three ways: (i) through the analysis of PKA
      dependent phenotypes, and (ii, iii) by measurement of PKA activity -/+ cAMP using
      the specific substrate kemptide in crude extracts (ii) and permeabilized cells
      (iii). Upon overexpression of the R subunits, PKA-dependent phenotypes were less
      severe when compared with their own background. However, a gradient in the degree
      of severity of phenotypes bcy1-14>bcy1-16> wild-type was observed in the
      background strains and was maintained in the strains overexpressing the R
      subunits. cAMP levels measured in background and in R-overexpressing strains
      showed an increase of around two orders accompanying the overexpression of the R
      subunits. Three main conclusions could be drawn from the PKA activity
      measurements -/+ cAMP in crude extracts: (i) catalytic activity was not increased
      in compensation for the increase in R subunits in any of the three cases (wild
      type, bcy1-16 or bcy1-14 overexpression); (ii) PKA activity assayed in the
      absence of cAMP was lower in the case of extracts from strains overexpressing
      wild-type or bcy1-16 R subunits when compared with the corresponding extracts
      without overexpression; and (iii) in these two cases, the great excess of R
      subunits in the crude extracts displayed additional inhibitory capacity towards
      exogenously added catalytic (C) subunits. To provide an estimate of the in vivo
      activation of PKA, permeabilized cells from control strains and strains
      transformed with either wild-type, bcy1-16 or bcy1-14 R subunits were used to
      measure PKA activity in the presence of variable concentrations of cAMP. There
      were two main observations from the results: (i) the activity of PKA detected in
      the absence of exogenous cAMP was decreased in the strains overexpressing the R
      subunits when compared to their corresponding backgrounds, and (ii) the
      sensitivity to activation by cAMP was decreased or almost nil. The biochemical
      and genetic results obtained are consistent with the hypothesis that within the
      cell it is possible to have catalytically active, cAMP-bound, undissociated PKA
      holoenzyme.

PMID- 11320119
TI  - Insertion of fluorescent fatty acid probes into the outer membranes of the
      pathogenic spirochaetes Treponema pallidum and Borrelia burgdorferi.
AB  - The authors examined the ability of octadecanoyl (C(18)), hexadecanoyl (C(16))
      and dodecanoyl (C(12)) fatty acid (FA) conjugates of 5-aminofluorescein (OAF, HAF
      and DAF, respectively) to insert into the outer membranes (OMs) of Treponema
      pallidum, Borrelia burgdorferi and Escherichia coli. Biophysical studies have
      demonstrated that these compounds stably insert into phospholipid bilayers with
      the acyl chain within the hydrophobic interior of the apical leaflet and the
      hydrophilic fluorescein moiety near the phospholipid head groups. Consistent with
      the known poor intrinsic permeability of the E. coli OM to hydrophobic compounds
      and surfactants, E. coli was not labelled with any of the FA probes. OAF inserted
      more readily into OMs of B. burgdorferi than into those of T. pallidum, although
      both organisms were completely labelled at concentrations at or below 2 microg
      ml(-1). Intact spirochaetes were labelled with OAF but not with antibodies
      against known periplasmic antigens, thereby confirming that the probe interacted
      exclusively with the spirochaetal OMs. Separate experiments in which organisms
      were cooled to 4 degrees C (i.e. below the OM phase-transition temperatures)
      indicated that labelling with OAF was due to insertion of the probe into the OMs.
      B. burgdorferi, but not T. pallidum, was labelled by relatively high
      concentrations of HAF and DAF. Taken as a whole, these findings support the
      prediction that the lack of lipopolysaccharide renders T. pallidum and B.
      burgdorferi OMs markedly more permeable to lipophilic compounds than their Gram
      negative bacterial counterparts. The data also raise the intriguing possibility
      that these two pathogenic spirochaetes obtain long-chain FAs, nutrients they are
      unable to synthesize, by direct permeation of their OMs.

PMID- 11320120
TI  - Highly conserved sequences flank avirulence genes: isolation of novel avirulence
      genes from Pseudomonas syringae pv. pisi.
AB  - DNA sequences flanking two avr genes (avrPpiA1 and avrPpiB1) from Pseudomonas
      syringae pv. pisi show a high degree of similarity. Specific primers designed
      from the conserved regions were used in PCR amplifications with all P. syringae
      pv. pisi races. As well as amplifying the expected avrPpiA- and avrPpiB
      containing fragments, two additional fragments were amplified: one contained a
      single open reading frame (ORF1) and was found in races of genomic group II (2,
      3A, 4A and 6); the second fragment contained two open reading frames (ORF2 and
      ORF3), separated by 658 nt, and was detected in all races. All three ORFs had G+C
      ratios (46.9-48 mol%) that were significantly less than that for P. syringae and
      each was preceded by a potential hrp box promoter. In P. syringae pv.
      phaseolicola, ORF1 and ORF2 each elicited a strong non-host hypersensitive
      reaction on bean leaves; ORF1 was designated avrPpiG, the product of which had
      strong similarity to AvrRxv, AvrBsT and YopP. ORF2 was identical to a gene,
      designated avrPpiC, previously isolated from P. syringae pv. pisi race 5. ORF3
      was always found in association with avrPpiC and both were detected in a wide
      range of P. syringae pathovars. In contrast, avrPpiG was only detected in strains
      of P. syringae pv. pisi genomic group II and P. syringae pv. coronafaciens (ICMP
      3113). In P. syringae pv. pisi, avrPpiG was plasmid-borne and avrPpiC and ORF3
      were chromosomal. This conservation of flanking sequences has implications for
      the horizontal transfer of avirulence and virulence genes, suggesting that
      specific regions of the bacterial genome act as sites for their
      integration/excision.

PMID- 11320121
TI  - Application of fibre-FISH (fluorescence in situ hybridization) to filamentous
      fungi: visualization of the rRNA gene cluster of the ascomycete Cochliobolus
      heterostrophus.
AB  - Fibre-FISH (fluorescence in situ hybridization) has not been used in filamentous
      fungi before to the authors' knowledge. In this study, this technique was applied
      to a filamentous ascomycete, Cochliobolus heterostrophus, to visualize the
      organization of the rRNA gene clusters (rDNA). Using protoplasts embedded in
      agarose, DNA fibres were released from interphase nuclei and extended on a glass
      slide. Four kinds of probes (0.5-9.0 kb in size) that correspond to specific
      regions in the repeat unit of rDNA were hybridized singly or in combination to
      the DNA fibres, and the hybridization was detected with fluorescein- and/or
      rhodamine-conjugated antibodies after one round of signal amplification. The
      alternating arrangement of 18S and 28S rRNA genes as well as the tandem
      repetitive nature of the repeat units were clearly visualized by this single- or
      two-colour fibre-FISH. With a probe targeting the 5.8S or 18S rRNA gene, a region
      spanning over 800 kb could be visualized in a single fibre, allowing estimation
      of both the copy number of the repeat unit in rDNA and the stretching degree of
      the DNA fibre. It was shown that C. heterostrophus has more than 90 copies of the
      repeat unit in its rDNA and the stretching degree was similar to the value based
      on the Watson-Crick model. Visualization of individual genes on an extended DNA
      fibre was accomplished in filamentous fungi by this study.

PMID- 11320122
TI  - Development of Streptococcus thermophilus lacZ as a reporter gene for Candida
      albicans.
AB  - The study of gene regulation in many organisms has been facilitated by the
      development of reporter genes. The authors report the use of lacZ from
      Streptococcus thermophilus, a gene encoding a beta-galactosidase, as a reporter
      for the fungal pathogen Candida albicans. As test cases, Strep. thermophilus lacZ
      was placed under control of three different C. albicans promoters: MAL2
      (maltase), inducible by maltose; HWP1 (hyphal cell wall protein), induced by
      conditions that promote filamentous growth; and ACT1 (actin). These constructs
      were each integrated into the C. albicans genome and beta-galactosidase activity
      was readily detected from these strains, but only under the appropriate growth
      conditions. Beta-galactosidase activity could be detected by several methods:
      quantitative liquid assays using permeabilized cells, colorimetric assays of
      colonies replicated to paper filters, and in situ coloration of colonies growing
      on medium containing the indicator X-Gal. These results show the usefulness of
      STREP: thermophilus lacZ as a monitor of gene regulation in this medically
      important yeast.

PMID- 11320123
TI  - Genomic analysis of the histidine kinase family in bacteria and archaea.
AB  - Two-component signal transduction systems, consisting of histidine kinase (HK)
      sensors and DNA-binding response regulators, allow bacteria and archaea to
      respond to diverse environmental stimuli. HKs possess a conserved domain (H-box
      region) which contains the site of phosphorylation and an ATP-binding kinase
      domain. In this study, a genomic approach was taken to analyse the HK family in
      bacteria and archaea. Based on phylogenetic analysis, differences in the sequence
      and organization of the H-box and kinase domains, and the predicted secondary
      structure of the H-box region, five major HK types were identified. Of the 336
      HKs analysed, 92% could be assigned to one of the five major HK types. The Type I
      HKs were found predominantly in bacteria while Type II HKs were not prevalent in
      bacteria but constituted the major type (13 of 15 HKs) in the archaeon
      Archaeoglobus fulgidus. Type III HKs were generally more prevalent in Gram
      positive bacteria and were the major HK type (14 of 15 HKs) in the archaeon
      Methanobacterium thermoautotrophicum. Type IV HKs represented a minor type found
      in bacteria. The fifth HK type was composed of the chemosensor HKs, CheA. Several
      bacterial genomes contained all five HK types. In contrast, archaeal genomes
      either contained a specific HK type or lacked HKs altogether. These findings
      suggest that the different HK types originated in bacteria and that specific HK
      types were acquired in archaea by horizontal gene transfer.

PMID- 11320124
TI  - A chromosome map of the European stone fruit yellows phytoplasma.
AB  - A physical map of the European stone fruit yellows phytoplasma strain GSFY1
      chromosome was constructed using PFGE-purified genomic DNA from diseased tobacco
      and tomato plants. The map was generated with single and double digestions of the
      chromosome with SmaI, BssHII, ApaI, BamHI and XhoI restriction endonucleases and
      the fragments were resolved by PFGE. Reciprocal double digestions were used to
      locate 26 restriction sites on the chromosome. Southern blot analysis was also
      used to assist in the arrangement of the contiguous restriction fragments
      obtained. From the restriction fragments generated by double digestion, the
      circular chromosome was calculated to be approximately 635 kb. Loci of two rRNA
      operons, the operon containing the tuf gene, genes encoding an immunodominant
      membrane protein and a putative nitroreductase, and randomly cloned DNA fragments
      IH184 and AT67 were placed on the map. Digestion of chromosomal DNA of strain
      GSFY1 with MluI gave a complex restriction pattern, suggesting that this isolate
      consists of a population with heterogeneity with respect to MluI restriction
      sites. The GSFY1 physical map was different from that of the closely related
      apple proliferation phytoplasma but the genetic arrangement was similar.

PMID- 11320125
TI  - Identity elements in tRNA-mediated transcription antitermination: implication of
      tRNA D- and T-arms in mRNA recognition.
AB  - tRNA-mediated transcription antitermination has been shown to control the
      expression of several amino acid biosynthesis operons and aminoacyl-tRNA
      synthetase-encoding genes in Gram-positive bacteria. A model originally put
      forward by Grundy & Henkin describes the conserved structural features of the
      leader sequences of these operons and genes. Two sequences of 3 and 4 nt,
      respectively, take a central position in this model and are thought to be
      responsible for the binding of the system-specific uncharged tRNA, an interaction
      which would stabilize the antiterminator conformation of the leader. Here a
      further evolution of this model is presented based on an analysis of trp
      regulation in Lactococcus lactis in which a function is assigned to hitherto
      unexplained conserved structures in the leader sequence. It is postulated that
      the mRNA-tRNA interaction involves various parts of the tRNA in addition to the
      anticodon and the acceptor in the original model and that these additional
      interactions contribute to the recognition of a specific tRNA, and hence to the
      specificity and efficacy of the regulatory response.

PMID- 11320126
TI  - Cyclic heptapeptide microcystin biosynthesis requires the glutamate racemase
      gene.
AB  - It was demonstrated previously that the operon consisting of the non-ribosomal
      peptide synthetase (NRPS) gene coupled with the polyketide synthase (PKS) gene
      involved in cyclic heptapeptide microcystin synthesis includes two different D
      amino acid synthetase genes, an epimerization domain at the 3' end of module 2,
      and the racemase gene mcyF. To determine the role of mcyF in microcystin
      synthesis, gene-disruption and complementation analyses were carried out.
      Insertional mutagenesis in the mcyF gene, generated by homologous recombination,
      abolished only microcystin synthesis, but did not influence cell growth.
      Furthermore, McyF supported D-Glu-independent growth of a strain of Escherichia
      coli defective in D-Glu synthesis. It is concluded that mcyF is the glutamic acid
      racemase gene involved in the synthesis of D-Glu residues in the microcystin
      molecule. This is the first report of the racemase in prokaryotic NRPS.

PMID- 11320127
TI  - Comparison of Tn5397 from Clostridium difficile, Tn916 from Enterococcus faecalis
      and the CW459tet(M) element from Clostridium perfringens shows that they have
      similar conjugation regions but different insertion and excision modules.
AB  - Comparative analysis of the conjugative transposons Tn5397 from Clostridium
      difficile and Tn916 from Enterococcus faecalis, and the CW459tet(M) element from
      Clostridium perfringens, has revealed that these tetracycline-resistance elements
      are closely related. All three elements contain the tet(M) resistance gene and
      have sequence similarity throughout their central region. However, they have very
      different integration/excision modules. Instead of the int and xis genes that are
      found in Tn916, Tn5397 has a large resolvase gene, tndX. The C. perfringens
      element encodes the putative Int459 protein, which is a member of the integrase
      family of site-specific recombinases but is not closely related to Int from
      Tn916. Based on these studies it is concluded that the clostridial elements have
      a modular genetic organization and were derived independently from distinct
      mobile genetic elements.

PMID- 11320128
TI  - Isolation of strong expression signals of Mycobacterium tuberculosis.
AB  - The natural fluorescence of the Aequoria victoria green fluorescent protein was
      exploited to isolate strong expression signals of Mycobacterium tuberculosis.
      Mycobacterium bovis bacille Calmette-Guerin harbouring M. tuberculosis fragments
      driving high levels of gfp expression were isolated by fluorescence-activated
      cell sorting (FACS). DNA sequencing and subsequent comparison with the M.
      tuberculosis genome sequence revealed that a total of nine postulated promoters
      had been identified. The majority of the promoters displayed activity that was
      greater than or equal to the Mycobacterium fortuitum beta-lactamase promoter, one
      of the strongest mycobacterial promoters characterized to date. Two of the
      promoters corresponded to proteins predicted to be involved in calcium and
      magnesium utilization, the importance of such functions for cell physiology
      suggesting why these two genes are controlled by strong transcription signals.
      The seven other promoters corresponded to genes encoding proteins of unknown
      function. Promoter activity was maintained after prolonged incubation within
      macrophages, implying that these promoters could be used to drive sustained
      foreign gene expression in vivo. The strength of these expression signals
      identified could be employed for the overexpression of foreign genes in
      mycobacteria to aid protein purification and vaccine vector development.
      Furthermore, this study demonstrated that FACS provides a sensitive and efficient
      technique to measure and select strong mycobacterial expression signals.

PMID- 11320129
TI  - zur: a Zn(2+)-responsive regulatory element of Staphylococcus aureus.
AB  - A putative operon encoding a probable zinc-responsive regulatory element (zur)
      and components of an ABC-type transporter (mreA mreB) have been characterized in
      Staphylococcus aureus. The zur gene was inactivated but apparently this did not
      alter Zn(2+) uptake. Expression of mreAB zur is at a low level under a range of
      ion conditions. To allow inducible expression of the operon, a construct was made
      placing it under the control of the IPTG-inducible P(spac) promoter. Using this
      approach, it was shown that zur is able to repress expression of the entire
      operon in a Zn(2+)-dependent manner, and that mreA and mreB are likely to be
      involved in high-affinity ion uptake. zur has no apparent role in pathogenicity
      in a lesion model of S. aureus infection.

PMID- 11320130
TI  - Lethality of glnD null mutations in Azotobacter vinelandii is suppressible by
      prevention of glutamine synthetase adenylylation.
AB  - GlnD is a pivotal protein in sensing intracellular levels of fixed nitrogen and
      has been best studied in enteric bacteria, where it reversibly uridylylates two
      related proteins, PII and GlnK. The uridylylation state of these proteins
      determines the activities of glutamine synthetase (GS) and NtrC. Results
      presented here demonstrate that glnD is an essential gene in Azotobacter
      vinelandii. Null glnD mutations were introduced into the A. vinelandii genome,
      but none could be stably maintained unless a second mutation was present that
      resulted in unregulated activity of GS. One mutation, gln-71, occurred
      spontaneously to give strain MV71, which failed to uridylylate the GlnK protein.
      The second, created by design, was glnAY407F (MV75), altering the adenylylation
      site of GS. The gln-71 mutation is probably located in glnE, encoding
      adenylyltransferase, because introducing the Escherichia coli glnE gene into
      MV72, a glnD(+) derivative of MV71, restored the regulation of GS activity. GlnK
      UMP is therefore apparently required for GS to be sufficiently deadenylylated in
      A. vinelandii for growth to occur. The DeltaglnD GS(c) isolates were Nif(-),
      which could be corrected by introducing a nifL mutation, confirming a role for
      GlnD in mediating nif gene regulation via some aspect of the NifL/NifA
      interaction. MV71 was unexpectedly NtrC(+), suggesting that A. vinelandii NtrC
      activity might be regulated differently than in enteric organisms.

PMID- 11320131
TI  - Neisserial TonB-dependent outer-membrane proteins: detection, regulation and
      distribution of three putative candidates identified from the genome sequences.
AB  - Computer searches were carried out of the gonococcal and meningococcal genome
      databases for previously unknown members of the TonB-dependent family (Tdf) of
      outer-membrane receptor proteins. Seven putative non-contiguous genes were found
      and three of these (identified in gonococcal strain FA1090) were chosen for
      further study. Consensus motif analysis of the peptide sequences was consistent
      with the three genes encoding TonB-dependent receptors. In view of the five
      previously characterized TonB-dependent proteins of pathogenic neisseriae, the
      putative genes were labelled tdfF, tdfG and tdfH. TdfF had homology with the
      siderophore receptors FpvA of Pseudomonas aeruginosa and FhuE of Escherichia
      coli, whereas TdfG and TdfH had homology with the haemophore receptor HasR of
      Serratia marcescens. The aim of this project was to characterize these proteins
      and determine their expression, regulation, distribution and surface exposure.
      Strain surveys of iron-stressed commensal and pathogenic neisseriae revealed that
      TdfF is unlikely to be expressed, TdfG is expressed by gonococci only and that
      TdfH is expressed by both meningococci and gonococci. Expression of TdfH was
      unaffected by iron availability. Susceptibility of TdfH to cleavage by proteases
      in live gonococci was consistent with surface exposure of this protein. TdfH may
      function as a TonB-dependent receptor for a non-iron nutrient source.
      Furthermore, TdfH is worthy of future investigation as a potential meningococcal
      vaccine candidate as it is a highly conserved, widely distributed and surface
      exposed outer-membrane protein.

PMID- 11320132
TI  - Expression of the gap gene encoding glyceraldehyde-3-phosphate dehydrogenase of
      Streptomyces aureofaciens requires GapR, a member of the AraC/XylS family of
      transcriptional activators.
AB  - Expression of the gap gene encoding glyceraldehyde-3-phosphate dehydrogenase
      (GAPDH) is developmentally regulated, and induced by glucose in Streptomyces
      aureofaciens. A gene, gapR, encoding a protein similar to the AraC/XylS family of
      bacterial transcriptional regulators was identified upstream of gap. The gapR
      gene was constitutively expressed from a single promoter during the course of
      differentiation. By integrative transformation, via double crossover, a stable
      null mutant of the gapR gene was obtained. The mutation only slightly affected
      growth, and had no effect on differentiation of S. aureofaciens. However,
      transcription of the GAPDH-encoding gap gene was substantially reduced in the S.
      aureofaciens DeltagapR null mutant, irrespective of carbon source used. Though
      GAPDH activity was about 1.5-fold lower in the mutant, the substantial enzyme
      activity remained, suggesting the presence of a second GAPDH which is sufficient
      to ensure growth. The GapR protein, overproduced in Escherichia coli, was shown
      to bind upstream of the gap-P promoter region. The results indicate a direct role
      of GapR in regulation of gap expression in S. aureofaciens.

PMID- 11320133
TI  - The Burkholderia cepacia fur gene: co-localization with omlA and absence of
      regulation by iron.
AB  - The ferric uptake regulator (Fur) functions as a transcription repressor of many
      genes in bacteria in response to iron, but the presence of a functional
      equivalent of this protein has not been demonstrated in Burkholderia cepacia. A
      segment of the Burkholderia pseudomallei fur gene was amplified using degenerate
      primers and used to identify chromosomal restriction fragments containing the
      entire fur genes of B. cepacia and B. pseudomallei. These fragments were cloned
      and sequenced, revealing the Fur protein of both species to be a polypeptide of
      142 amino acids possessing a high degree of amino acid sequence identity to Fur
      of other members of the beta subclass of the Proteobacteria. Primer extension
      analysis demonstrated that transcription of B. cepacia fur originated from a
      single promoter located 36 bp upstream from the fur translation initiation codon.
      The Fur polypeptide of B. cepacia was shown to functionally substitute for Fur in
      an Escherichia coli fur mutant. Single copy fur-lacZ fusions were constructed and
      used to examine the regulation of B. cepacia fur. The B. cepacia fur promoter was
      not responsive to iron availability, the presence of hydrogen peroxide or the
      superoxide generator methyl viologen. In addition, fur expression was not
      significantly influenced by carbon source. Interestingly, the presence of the
      divergently transcribed omlA/smpA gene upstream of fur in some members of the
      gamma subclass of the Proteobacteria is retained in several genera within the
      beta taxon, including Burkholderia.

PMID- 11320134
TI  - The bio operon on the acquired symbiosis island of Mesorhizobium sp. strain R7A
      includes a novel gene involved in pimeloyl-CoA synthesis.
AB  - The symbiosis island of Mesorhizobium sp. strain R7A is a 500 kb chromosomal
      genetic element that upon transfer converts nonsymbiotic mesorhizobia to
      symbionts able to nodulate and fix nitrogen with Lotus corniculatus. Four genomic
      species of nonsymbiotic mesorhizobia have been isolated. All were auxotrophic for
      thiamin and biotin and three were auxotrophic for nicotinate, whereas derivatives
      of the strains containing the symbiosis island were prototrophic for all three
      vitamins. In this work, a 13.2 kb region of the island that converts the
      nonsymbionts to nicotinate and biotin prototrophy was characterized. The region
      contained orthologues of the Escherichia coli bioBFD and A genes arranged in an
      operon with a novel gene, bioZ, a nadABC operon, the nitrogen-fixation regulatory
      gene nifA, and a homologue of the pantothenate biosynthesis gene panD. The bioZ
      gene product was similar to beta-ketoacyl-acyl carrier protein synthase III
      (FabH). bioZ::Tn5 mutants grew poorly in the absence of biotin and the bioZ gene
      complemented an E. coli bioH mutant, suggesting that its product is involved in
      the synthesis of pimeloyl-COA: The bio operon was not required for symbiosis, as
      only mutants in the nifA gene were impaired in symbiosis, and a bioA::Tn5 mutant
      was not impaired in rhizosphere colonization. The rationale for the vitamin
      biosynthetic loci being located on an acquired genetic element that is absent
      from nonsymbiotic mesorhizobia remains to be determined.

PMID- 11320135
TI  - Molecular characterization of Pseudomonas putida KT2440 rpoH gene regulation.
AB  - The rpoH gene of Pseudomonas putida KT2440 encoding the heat-shock sigma factor
      sigma(32) was cloned and sequenced, and the translated gene product was predicted
      to be a protein of 32.5 kDa. The unambiguous role of the gene as a sigma factor
      was confirmed because the cloned P. putida gene complemented the growth defect,
      at 37 and 42 degrees C, of an Escherichia coli rpoH mutant strain. Primer
      extension analysis showed that in P. putida the rpoH gene is expressed from three
      promoters in cells growing at 30 degrees C. Two of them, P1 and P3, share
      homology with the sigma(70)-dependent promoters, while the third one, P2, shows a
      typical sigma(24)-consensus sequence. The pattern of transcription initiation of
      the rpoH gene did not change in response to different stresses, i.e. a sudden
      heat shock or the addition of aromatic compounds. However, the predicted
      secondary structure of the 5' region of the mRNA derived from the three different
      promoters suggests regulation at the level of translation efficiency and/or mRNA
      half-life. An inverted repeat sequence located 20 bp downstream of the rpoH stop
      codon was shown to function as a terminator in vivo in P. putida growing at
      temperatures from 18 to 42 degrees C.

PMID- 11320136
TI  - Transcripts of the genes sacB, amyE, sacC and csn expressed in Bacillus subtilis
      under the control of the 5' untranslated sacR region display different
      stabilities that can be modulated.
AB  - When Bacillus subtilis levanase (SacC), alpha-amylase (AmyE) and chitosanase
      (Csn) structural genes were expressed under the regulated control of sacR, the
      inducible levansucrase (SacB) leader region in a degU32(Hy) mutant, it was
      observed that the production yields of the various extracellular proteins were
      quite different. This is mainly due to differences in the stabilities of their
      corresponding mRNAs which lead to discrepancies between the steady-state level of
      mRNA of sacB and csn on the one hand and amyE and sacC on the other. In contrast
      to levansucrase mRNA, the decay curves of alpha-amylase and levanase mRNAs
      obtained by Northern blotting analysis did not match the decay curves of their
      functional mRNA. This suggested that only a part of the population of the amyE
      and sacC transcripts was fully translated, while the others were possibly poorly
      bound to ribosomes and thus were only partially translated or not at all and
      consequently submitted to rapid endonuclease degradation. This hypothesis was
      substantiated by the finding that the introduction of a Shine-Dalgarno sequence
      upstream from the ribosome-binding site in the sacC transcript resulted in a
      fourfold increase in both the half-life of this transcript and the production of
      levanase. An additional cause of low-level levanase production is the premature
      release of mRNA by the polymerase. It was attempted to correlate this event with
      internal secondary structures of sacC mRNA.

PMID- 11320137
TI  - A general strategy for identification of S-layer genes in the Bacillus cereus
      group: molecular characterization of such a gene in Bacillus thuringiensis subsp.
      galleriae NRRL 4045.
AB  - Despite its possible role in virulence, there has been little molecular
      characterization of members of the S-layer protein family of the Bacillus cereus
      group. It is hypothesized that the components of the S-layers are likely to
      display similar anchoring structures in Bacillus thuringiensis and Bacillus
      anthracis. Based on inferred sequence similarities, a DNA fragment encoding the
      cell-wall-anchoring domain of an S-layer component of BAC: thuringiensis subsp.
      galleriae NRRL 4045 was isolated. The complete gene was identified and sequenced.
      An ORF of 2463 nt was identified, which was predicted to encode a protein of 821
      aa, SlpA. The mature SlpA protein (792 residues) carries three S-layer homology
      (SLH) motifs towards its amino terminus, each about 50 aa long. These motifs were
      sufficient to bind Bac. thuringiensis and Bac. anthracis cell walls in vitro by
      interacting with peptidoglycan-associated polymers, confirming a common wall
      anchoring mechanism. The slpA null-allele mutant was constructed and shown to
      possess no other abundant surface protein. It is proposed that the method
      described in this paper could be applied to the identification and deletion of
      any Bac. cereus S-layer gene and is of great value for the molecular and
      functional characterization of these genes.

PMID- 11320138
TI  - Analysis of the structure-function relationship of the S-layer protein SbsC of
      Bacillus stearothermophilus ATCC 12980 by producing truncated forms.
AB  - The mature surface layer (S-layer) protein SbsC of Bacillus stearothermophilus
      ATCC 12980 comprises amino acids 31-1099 and self-assembles into an oblique
      lattice type which functions as an adhesion site for a cell-associated high
      molecular-mass exoamylase. To elucidate the structure-function relationship of
      distinct segments of SbsC, three N- and seven C-terminal truncations were
      produced in a heterologous expression system, isolated, purified and their
      properties compared with those of the recombinant mature S-layer protein rSbsC(31
      1099). With the various truncated forms it could be demonstrated that the N
      terminal part (aa 31-257) is responsible for anchoring the S-layer subunits via a
      distinct type of secondary cell wall polymer to the rigid cell wall layer, but
      this positively charged segment is not required for the self-assembly of SbsC,
      nor for generating the oblique lattice structure. If present, the N-terminal part
      leads to the formation of in vitro double-layer self-assembly products. Affinity
      studies further showed that the N-terminal part includes an exoamylase-binding
      site. Interestingly, the N-terminal part carries two sequences of 6 and 7 aa
      (AKAALD and KAAYEAA) that were also identified on the amylase-binding protein
      AbpA of Streptococcus gordonii. In contrast to the self-assembling N-terminal
      truncation rSbsC(258-1099), two further N-terminal truncations (rSbsC(343-1099),
      rSbsC(447-1099)) and three C-terminal truncations (rSbsC(31-713), rSbsC(31-844),
      rSbsC(31-860)) had lost the ability to self-assemble and stayed in the water
      soluble state. Studies with the self-assembling C-terminal truncations rSbsC(31
      880), rSbsC(31-900) and rSbsC(31-920) revealed that the C-terminal 219 aa can be
      deleted without interfering with the self-assembly process, while the C-terminal
      179 aa are not required for the formation of the oblique lattice structure.

PMID- 11320140
TI  - Assessment of GFP fluorescence in cells of Streptococcus gordonii under
      conditions of low pH and low oxygen concentration.
AB  - Use of green fluorescent protein (GFP) as a molecular reporter is restricted by
      several environmental factors, such as its requirement for oxygen in the
      development of the fluorophore, and its poor fluorescence at low pH. There are
      conflicting data on these limitations, however, and systematic studies to assess
      the importance of these factors for growing bacterial cultures are lacking. In
      the present study, homogeneous expression of the gfpmut3* gene directed by a
      synthetic constitutive lactococcal promoter was demonstrated in batch cultures
      and in biofilms of Streptococcus gordonii DL1. A lower limit of oxygen
      concentration for maturation of the GFP fluorophore was determined: fluorescence
      was emitted at 0.1 p.p.m. dissolved oxygen (in conventionally prepared anaerobic
      media lacking reducing agents), whereas no fluorescence was detected in the
      presence of 0.025 p.p.m. dissolved oxygen (obtained by addition of L-cysteine as
      reducing agent). When an anaerobically grown (non-fluorescent) >50 microm thick
      biofilm was shifted to aerobic conditions, fluorescence could be detected within
      4 min, reaching a maximum over the next 16 min. It was not possible to detect any
      fluorescence gradients (lateral or vertical) within the >50 microm thick biofilm,
      and fluorescence development after the shift to aerobic conditions occurred
      throughout the biofilm (even at the substratum). This suggests that oxygen
      gradients, which might result in reduced GFP fluorescence, did not exist in the
      >50 microm thick biofilm of this organism. Production of lactic acid and the
      subsequent acidification in batch cultures of S. gordonii DL1 led to a decrease
      in fluorescence intensity. However, severe pH reduction was prevented when the
      bacterium was grown as a biofilm in a flowcell, and a homogeneous distribution of
      a strong fluorescence signal was observed. These findings show that GFP can be
      applied to studies of oxygen-tolerant anaerobic bacteria, that densely packed,
      flowcell-grown biofilms of S. gordonii do not develop oxygen gradients inhibitory
      to GFP fluorescence development, and that the often transient nature of GFP
      fluorescence in acid-producing bacteria can be overcome in flowcells, probably by
      the elimination of metabolic by-product accumulation.

PMID- 11320139
TI  - Structure of the cell envelope of corynebacteria: importance of the non
      covalently bound lipids in the formation of the cell wall permeability barrier
      and fracture plane.
AB  - With the recent success of the heterologous expression of mycobacterial antigens
      in corynebacteria, in addition to the importance of these bacteria in
      biotechnology and medicine, a better understanding of the structure of their cell
      envelopes was needed. A combination of molecular compositional analysis,
      ultrastructural appearance and freeze-etch electron microscopy study was used to
      arrive at a chemical model, unique to corynebacteria but consistent with their
      phylogenetic relatedness to mycobacteria and other members of the distinctive
      suprageneric actinomycete taxon. Transmission electron microscopy and chemical
      analyses showed that the cell envelopes of the representative strains of
      corynebacteria examined consisted of (i) an outer layer composed of
      polysaccharides (primarily a high-molecular-mass glucan and arabinomannans),
      proteins, which include the mycoloyltransferase PS1, and lipids; (ii) a cell wall
      glycan core of peptidoglycan-arabinogalactan which may contain other sugar
      residues and was usually esterified by corynomycolic acids; and (iii) a typical
      plasma membrane bilayer. Freeze-etch electron microscopy showed that most
      corynomycolate-containing strains exhibited a main fracture plane in their cell
      wall and contained low-molecular-mass porins, while the fracture occurred within
      the plasma membrane of strains devoid of both corynomycolate and pore-forming
      proteins. Importantly, in most strains, the amount of cell wall-linked
      corynomycolates was not sufficient to cover the bacterial surface; interestingly,
      the occurrence of a cell wall fracture plane correlated with the amount of non
      covalently bound lipids of the strains. Furthermore, these lipids were shown to
      spontaneously form liposomes, indicating that they may participate in a bilayer
      structure. Altogether, the data suggested that the cell wall permeability barrier
      in corynebacteria involved both covalently linked corynomycolates and non
      covalently bound lipids of their cell envelopes.

PMID- 11320141
TI  - Micronucleus induction and chromosomal aberration of 1- and 3
      nitroazabenzo[a]pyrene and their N-oxides.
AB  - Nitro-azabenzo[a]pyrenes, 1- or 3-nitro-azabenzo[a]pyrene and their N-oxides are
      nitrated derivatives of azabenzo[a] pyrene (ABP) containing nitrogen in the 6
      position of benzo[a]pyrene (B[a]P). The nitro-ABP-N-oxides (ABPOs) were formed by
      reaction of ABP with excess HNO(3). These derivatives were noteworthy as potent
      mutagens for Salmonella strains, and were present in fine particles of diesel
      particulates. In this study, micronucleus induction in mice and chromosomal
      aberrations due to means of Chinese hamster lung fibroblast (CHL) cells were
      investigated to determine genotoxicity in order to define the relationship with
      the mutagenic potency of these derivatives. The induction of micronucleus
      polychromatic erythrocytes (MNPCEs) was dependent on the dose response of 10-40
      mg for 3-N-6-ABP, and of 10-40 mg for 1-N-6-ABP, and in addition, 1- and 3-N-6
      ABPOs markedly induced MNPCEs in a dose range of 10-400 mg and from 1 to 80 mg,
      respectively, when the compound was intraperitoneally administrated in two mice
      at each dose. The results show that of the four compounds, 3-N-6-ABPO
      demonstrated a marked increase in MNPCES: On the other hand, chromosomal
      aberrations of the four compounds were investigated by the duplicate tests using
      CHLS: The results after a 48 h treatment induced aberrations of the chromatid
      type, chromatid breaks and exchanges for 1- and 3-N-6-ABP, and mainly chromatid
      exchanges for 1- and 3-N-6-ABPO. The frequency of chromosomal aberrations
      associated with nitro substitution on the ABPO structure. Chromosomal aberrations
      of nitro derivatives of ABPO substituted at the 3-position on the structure were
      more potent than those at the 1-postion. N-oxide derivatives have been found to
      be reduced to anion radicals much more easily than azaB[a]P and its nitro
      derivatives. This suggests that the electrochemical reduction of the chemicals
      plays an important role in the metabolic activation of nitrated B[a]P
      derivatives.

PMID- 11320142
TI  - Evaluation of inter-scorer and inter-laboratory reliability of the mouse
      epididymal sperm aneuploidy (m-ESA) assay.
AB  - The mouse epididymal sperm aneuploidy (mESA) assay using 3-chromosome
      fluorescence in situ hybridization (FISH) was recently developed for assessing
      the aneugenic potential of chemicals on male germ cells. This study was designed
      to identify the major technical factors that affect inter-scorer and inter
      laboratory variability of the mESA assay. Two laboratories participated in this
      study (GSF and Lawrence Livermore National Laboratory, LLNL). Mice
      (102/ElxC3H/El) F(1) were exposed in one laboratory (GSF) to vinblastine (VBL;
      single intraperitoneal injection of 0, 0.5, 1.0 or 2.0 mg/kg), one of the 10
      priority compounds of the Commission of the European Communities (CEC) Aneuploidy
      Program. Twenty-two days later the mESA assay was applied to analyze sperm
      aneuploidy. In the initial evaluation, small but statistically significant
      differences were found between the two laboratories in baseline frequencies and
      there was also disagreement in the determination of a VBL aneuploid effect.
      Therefore, experiments were conducted to identify the sources of the inter
      laboratory differences and technical factors that affected assay reliability and
      the VBL study was repeated. A harmonization experiment was conducted by bringing
      the microscope scorers from both laboratories to the same site (LLNL) for a cross
      training exercise. Following this exercise, a second group of VBL-treated and
      control mice were evaluated, and we concluded that VBL is not a sperm aneugen.
      Our research has identified scoring criteria as the major source of inter
      laboratory variation and emphasizes the importance of strict technical controls
      for the mESA assay, including controlling slide preparations for treatment
      induced reductions in sperm count, coding of slides and selection of statistical
      tests. These considerations are particularly important for the interpretation of
      small effects (< or =2-fold) on sperm aneuploidy. Our findings suggest that 2
      fold differences in frequencies can result from differences among scorers,
      samples and treatment groups, and are readily within the normal variation for the
      mESA assay. Such small differences should be viewed with caution until
      independently confirmed.

PMID- 11320143
TI  - Induction of mutant lymphocytes in cyclophosphamide- and chlorambucil-treated
      patients.
AB  - Monitoring patients treated with single antineoplastic agents is aiding our
      understanding of what hazard these drugs pose in vivo. In this study, the
      frequency of mutant 6-thioguanine-resistant (TG(R)) peripheral blood lymphocytes
      was monitored before treatment and for < or =35 weeks after treatment of patients
      with cyclophosphamide (CP) or chlorambucil (CAB). The mean mutant frequency
      before treatment for six multiple sclerosis patients treated with high-dose CP
      was 2.53 x 10(-5) and increased after treatment to 4.61 x 10(-5) (P = 0.08,
      paired t-test). Using each patient as their own control, there were significant
      increases (each at P < 0.04) detectable within 2-4 weeks in four of the multiple
      sclerosis patients treated with CP. There was no increase in an untreated control
      monitored over the same period. In a patient receiving five sequential CP
      treatments at 1 month intervals, there were cumulative increases in the frequency
      of mutant cells. The mutant frequency increased from 0.31 x 10(-5) before
      treatment to 3.64 x 10(-5) after the final treatment and had decreased to 0.53 x
      10(-5) at 35 weeks after treatment. In one of two CAB-treated patients with
      indolent non-Hodgkin's lymphoma, there was a significant increase in mutant
      frequency (P < 0.03) after treatment. Freshly isolated peripheral blood
      lymphocytes treated with 4-hydroperoxy-CP in vitro demonstrate a dose-dependent
      increase in mutant frequency. The increment in mutant frequency observed in vivo
      is of the order expected from the in vitro experiments. Although this study
      demonstrates that single or multiple doses of a single antineoplastic agent are
      mutagenic in vivo for some patients, further studies are needed to determine the
      extent and mechanism of the inter-individual variations in mutagenic response.

PMID- 11320144
TI  - Enhancement of genetic instability in human B cells by Epstein-Barr virus latent
      infection.
AB  - The level of genetic instability, as assessed by micronucleus (MN) formation, was
      higher in Epstein-Barr virus (EBV)-converted B-cell lines with one copy of the
      EBV genome integrated in each cell than in the parental, EBV-negative, B lymphoma
      cells. MN induced by EBV latency, as analysed by in situ hybridization, contained
      mainly centromeric regions, indicating that the presence of EBV affects the
      segregation of entire chromosomes. The instability was inhibited by treatment
      with antioxidants. Flow cytometric analysis indicated that there was a higher
      basal level of peroxides in EBV(+) cells. Direct oxidative stress caused by
      hydrogen peroxide (which is known to be both apoptogenic and mutagenic) enhanced
      the number of MN only in an EBV-converted clone. These cells were also resistant
      to apoptosis, as expected, suggesting that in the parental EBV cells apoptosis
      may efficiently eliminate cells with genetic damage. These results show for the
      first time a direct involvement of EBV in the induction of genetic instability,
      suggesting that it could contribute to tumour progression.

PMID- 11320145
TI  - Increased formation of micronuclei after hormonal stimulation of cell
      proliferation in human breast cancer cells.
AB  - The carcinogenicity of sex hormones is considered to be the result of a
      combination of genotoxic and epigenetic modes of action. For estrogens, genotoxic
      activities include DNA damage by reactive metabolites and indirect genotoxicity
      by redox cycling and production of reactive oxygen species. Here, we present data
      on the induction of micronuclei in estrogen receptor-positive (MCF-7) and 
      negative (MDA) human breast cancer cell lines treated with estradiol to support
      an additional mechanism of chromosomal damage. MCF-7 cells, but not MDA cells,
      treated with estradiol in the picomolar concentration range showed an increase in
      micronucleus formation which correlated with the estradiol-induced cell
      proliferation. Addition of the specific estradiol-receptor antagonist
      hydroxytamoxifen suppressed the estradiol-induced formation of micronuclei in MCF
      7 cells. Increased frequencies were also seen after normalization of the data to
      the number of cell divisions by additional treatment of the cells with
      cytochalasin B. Thus, formation of micronuclei was not due to the chromosomal
      damaging activity of estradiol. The induced genomic damage may be explained by a
      hormone-specific forcing of responsive cells through the cell cycle, thereby
      overriding checkpoints operating under homeostatic control of the cell cycle.

PMID- 11320146
TI  - Preliminary study of the genotoxic potential of homocysteine in human lymphocytes
      in vitro.
AB  - Homocysteine (Hcy), an immediate precursor of methionine (Met), is considered a
      risk factor for cardiovascular disease, Alzheimer's disease and neural tube
      defects. Hcy concentration is also reported to correlate positively with the
      micronucleus index in lymphocytes in vivo, a marker of chromosome damage.
      However, it is unclear whether Hcy is genotoxic or simply a biomarker of folate
      deficiency, a known cause of chromosome damage. We investigated whether high
      concentrations of Hcy are genotoxic to human lymphocytes in vitro using the
      cytokinesis-block micronucleus assay. Eighteen lymphocyte cultures were initiated
      in Met-free and serum-free RPMI 1640 medium for each of four male volunteers aged
      22-23 years. At 0, 24, 44 and 72 h, cultures were spiked with L-Hcy or L-Met to
      achieve concentrations ranging between 50 and 400 microM. The concentration of
      Hcy at 96 h ranged from 19.45 +/- 2.34 to 149.02 +/- 28.16 microM in Hcy cultures
      and 0.91 +/- 0.17 to 2.15 +/- 0.9 microM in Met cultures spiked with 50 and 400
      microM of metabolite, respectively. Forty-four hours after mitogen stimulation,
      cytokinesis was inhibited with cytochalasin B. After 96 h, cells were transferred
      to microscope slides and the frequency of micronucleated-binucleate and necrotic
      cells was scored. Neither Hcy (P = 0.24) nor Met (P = 0.93) had an apparent dose
      effect on micronucleus frequency. However, when data were pooled, micronucleus
      frequency was moderately higher (50.1%) in Hcy- than in Met-spiked cultures (P =
      0.04; paired t-test). Hcy concentration was positively correlated with necrosis
      (P < 0.0005; r(2)= 0.276), however, when data were pooled, levels of necrosis
      were higher in Met- than in Hcy-spiked cultures (P= 0.01; paired t-test). Further
      research is required to define more clearly the genotoxic and cytotoxic potential
      of homocysteine and its metabolites.

PMID- 11320147
TI  - Assessment of genotoxic damage by the comet assay in white storks (Ciconia
      ciconia) after the Donana Ecological Disaster.
AB  - Single cell gel electrophoresis, the so-called "Comet" assay, was performed as a
      genotoxicity test in white storks sampled in an area heavily contaminated after
      the ecological disaster in south western Spain. This disaster occurred as a
      consequence of a massive toxic spillage of acid waste rich in heavy metals that
      impacted on the Donana National Park. The importance of this protected area as a
      breeding and wintering site for many endangered bird species makes this analysis
      of DNA damage of special interest. Our results clearly show that white storks
      born in the contaminated area 1 year after the toxic spill bear a high burden of
      genetic damage as compared with control individuals. The possible implications
      for future survival as well as reproductive rate are discussed.

PMID- 11320148
TI  - Analysis of repair and PCNA complex formation induced by ionizing radiation in
      human fibroblast cell lines.
AB  - Proliferating cell nuclear antigen (PCNA), an auxiliary factor for DNA polymerase
      delta and epsilon, is involved in both DNA replication and repair. Previous
      studies in vitro have demonstrated the requirement of PCNA in the resynthesis
      step of nucleotide excision repair (NER) and base excision repair (BER). Using a
      native chromatin template isolated under near physiological conditions, we have
      analysed the involvement of PCNA in the BER pathway in different NER defective
      human cell lines. The repair sites and PCNA were visualized by indirect
      immunolabelling followed by fluorescence microscopy. The results indicate that
      exposure to X-rays triggers the induction of PCNA in all the three human
      fibroblast cell lines studied, namely normal, xeroderma pigmentosum group A (XP
      A) and Cockayne syndrome group B (CS-B). In all the cell lines, induction of PCNA
      and repair patches occurred in a dose- and time-dependent fashion. Induction of
      repair patches in NER-deficient XP-A cells suggests that the X-ray-induced
      lesions are largely repaired via the BER pathway involving PCNA as one of the key
      components of this pathway. X-ray-induced repair synthesis was greatly inhibited
      by treatment of cells with DNA polymerase inhibitors aphidicolin and cytosine
      arabinoside. Interestingly, inhibition of repair resynthesis did not affect the
      intensity of PCNA staining in X-irradiated cells indicating that the PCNA may be
      required for the BER pathway at a step preceding the resynthesis step.

PMID- 11320149
TI  - Effect of ultraviolet light, methyl methanesulfonate and ionizing radiation on
      the genotoxic response and apoptosis of mouse fibroblasts lacking c-Fos, p53 or
      both.
AB  - c-Fos and p53 are DNA damage-inducible proteins that are involved in gene
      regulation, cell cycle checkpoint control and cell proliferation following
      exposure to genotoxic agents. To investigate comparatively the role of c-Fos and
      p53 in the maintenance of genomic stability and the induction of apoptosis, we
      generated mouse fibroblast cell lines from knockout mice deficient for either c
      fos (fos -/-) or p53 (p53-/-) or for both gene products (fosp53-/-). The
      sensitivity of these established cell lines was compared with the corresponding
      wild-type cells as to the cytotoxic, clastogenic and apoptosis-inducing effects
      of ultraviolet (UV-C) light and methyl methanesulfonate (MMS). Additionally, we
      analysed the frequency of apoptosis of the cell lines after treatment with
      ionizing radiation (IR). We observed c-fos-/-, p53-/- and fosp53-/- cells to be
      more sensitive than wild-type cells with respect to cell death, as measured in a
      cytotoxicity (MTT) assay. Regarding apoptosis, all deficient cell lines displayed
      hypersensitivity to UV-C light, MMS and IR. With chromosomal aberrations as the
      endpoint, the sensitivity of the double-knockout cells was between wild-type and
      single-knockouts. The results indicate that both c-Fos and p53 play an important
      role in protecting fibroblasts against a broad range of genotoxic agents. The
      results also show that, in fibroblasts, apoptosis induced by UV-C light, MMS and
      IR does not require p53 and that, in this cell type, p53 rather protects against
      DNA damage-induced apoptotic cell death.

PMID- 11320150
TI  - Apoptosis can be a confusing factor in in vitro clastogenic assays.
AB  - Among the tests used to determine the mutagenic potential of chemicals, the
      chromosomal aberrations and micronucleus assays play an important role. These
      tests score either chromosomal structural aberrations at metaphase or micronuclei
      at interphase. One of the hallmarks of apoptosis is DNA fragmentation into 50-300
      kpb leading to oligonucleosomal fragmentation that can interfere with the results
      of clastogenic assays. In this case, apoptosis may be a confusing factor in the
      evaluation of the mutagenic potential of molecules and lead to false positive
      results. For these reasons we have developed a cell line able to demonstrate the
      interference of apoptosis in two mutagenicity tests: the in vitro micronucleus
      test and metaphase analysis in vitro. We used a murine cytotoxic T cell line,
      CTLL-2 Bcl2, in which a stably transfected bcl2 gene is known to protect these
      cells from apoptosis induced by various stimuli. A comparison between results
      obtained in parental CTLL-2 cells and in CTLL-2 Bcl2 cells treated with non
      genotoxic apoptosis inducers, such as dexamethasone or gliotoxin, leads us to
      conclude that apoptosis could give false positive results due to DNA
      fragmentation. Moreover, with etoposide, a clastogen that also induces apoptosis,
      we observed that the percentages of aberrant cells and numbers of micronuclei
      were significantly increased in CTLL-2 cells compared with CTLL-2 Bcl2 cells.
      This observation suggests that apoptosis leads to an overestimation of the
      genotoxic potential of chemicals. Finally, with nocodazole, an aneugen, we
      confirm that this model can also detect agents that have only genotoxic potential
      and thus allows a better estimation of the genotoxic threshold in studies with
      aneugens, thus avoiding overestimation of the mutagenic risk of such a compound.

PMID- 11320152
TI  - Inducible protective processes in animal systems: VIII. Enhancement of adaptive
      response by nicotinamide.
AB  - The molecular mechanism of the adaptive response or inducible DNA repair process
      has not been clearly demonstrated in eukaryotic systems. The involvement of
      poly(ADP-ribose) polymerase (PARP), a DNA repair enzyme has been reported in the
      adaptive response (Shadley and Wolff, 1987; Wiencke, 1987). Hence, the present
      studies were undertaken to understand the role of PARP in ethyl methanesulfonate
      (EMS)-induced adaptive response in mouse bone marrow cells by employing the
      inhibitor of this enzyme, nicotinamide. Inter-, pre- and post-treatments of
      nicotinamide with EMS were made. The results have revealed that there is a
      reduction in the frequencies of chromosomal aberrations compared with combined or
      challenge treatment at the different recovery times tested. These results are
      discussed with reference to the enhancement of the adaptive response by
      nicotinamide in mouse bone marrow cells.

PMID- 11320151
TI  - Dynamics of changes in micronucleus frequencies in subjects post cessation of
      chronic low-dose radiation exposure.
AB  - To assess DNA damage remaining in peripheral lymphocytes, 48 individuals were
      evaluated twice for lymphocyte micronucleus frequencies by the cytokinesis
      blocking cytochalasin B (CBMN) analysis post relocation from radio-contaminated
      apartments after various periods of time. The frequencies of CBMN at the first
      evaluation were significantly higher than those at the second examination (Chang
      et al., 1999c). These individuals were categorized into three groups: those with
      cumulative exposure of >300 mSv (defined as high exposure, HDose), those with 100
      300 mSv (MDose) and those with <100 mSv (LDose). Using the Poisson mixed-effect
      model (Little et al., 1996), the estimated mean CBMN frequencies ( per thousand)
      for individuals in HDose, MDose and LDose exposure categories when they had only
      recently relocated were 21.8, 17.6 and 15.4, respectively. The estimated mean
      duration post relocation for the CBMN frequencies of these individuals to reduce
      to 10.2, the second CBMN frequency, on average, was 47.5, 37.2 and 28.3 months in
      the three exposure groups, respectively. The rates of change in CBMN frequencies
      were shown to be significantly higher in the HDose group than in the MDose and
      LDose groups. The results suggested a characteristic dose-dependent decline in
      the CBMN frequencies in the exposed population post cessation of chronic low-dose
      ionizing radiation exposure.

PMID- 11320153
TI  - Is the capacity of lead acetate and cadmium chloride to induce genotoxic damage
      due to direct DNA-metal interaction?
AB  - Even though the toxic effects of lead and cadmium compounds have been studied
      over many years, inconsistent results have been obtained about their mutagenic,
      clastogenic and carcinogenic properties. However, these metals are considered to
      be potential human carcinogens. The mechanism of metal-induced carcinogenesis is
      still unknown, but one possible pathway may involve the interaction of metals
      with DNA, either directly or indirectly. In this work we explore the capacity of
      lead, cadmium or a mixture of both metals to interact with acellular DNA, by
      employing a variant of the comet assay. Our results, using low non-cytotoxic
      metal concentrations (0.01, 0.1 and 1.0 microM) with the standard protocol for
      the acellular assay, showed an induction of DNA damage in cells of all organs
      studied; however, basal DNA damage was different in each organ. To confirm that
      we were working with pure DNA, proteinase K was added to the lysis solution. With
      this enriched-lysis solution we found a negative response in the induction of DNA
      damage in cells derived from the liver, kidney and lung of CD-1 male mice. To
      support the results obtained by the enriched-acellular assay, we studied the
      capacity of lead and cadmium (0.1 microM) to induce breaks in pooled genomic DNA
      in cells of the same organs, with negative results. Consistent with these
      findings, these metals do not induce DNA breaks in the plasmid pUSE amp+. On the
      whole, we did not detect direct induction of DNA strand breaks by lead acetate,
      cadmium chloride or a mixture of both metals, all at low non-cytotoxic
      concentrations. However, we found an induction of lipid peroxidation and an
      increase in free radical levels in the different organs of CD-1 male mice after
      inhalation of lead acetate (0.0068 microg/cc) or cadmium chloride (0.08
      microg/cc) for 1 h, suggesting the induction of genotoxicity and carcinogenicity
      by indirect interactions, such as oxidative stress.

PMID- 11320154
TI  - Fast repair of the radical cations of dCMP and poly C by quercetin and rutin.
AB  - The effects of quercetin and rutin on the repair of the radical cations of dCMP
      and poly C were studied using the technique of pulse radiolysis. The radical
      cations of dCMP and poly C were formed by the reaction of dCMP and poly C with
      SO( 4)(-). After pulse irradiation of nitrogen-saturated aqueous solutions
      containing dCMP, 20 mM K(2)S(2)O(8), 200 mM t-BuOH and either rutin or quercetin,
      the initially formed radical cation of dCMP, detected spectrophotometrically,
      rapidly decayed with the concurrent formation of the phenoxyl radical of rutin or
      quercetin within 8-40 micros. The repair efficiencies of the tested compounds
      towards the poly C radical cation were also determined using the same procedure.
      The results indicate that dCMP and poly C radical cations can be rapidly repaired
      by quercetin and rutin. The rate constants of the repair reactions were
      determined to be 4.3-8.8x10(8) M/s and 1.5-3.6x10(8) M/s for dCMP and poly C
      radical cations, respectively. Together with findings from our previous studies,
      the present results demonstrate that non-enzymatic fast repair may be a universal
      form of repair involving phenolic antioxidants.

PMID- 11320155
TI  - Trans-stilbene oxide-induced sister chromatid exchange in cultured human
      lymphocytes: influence of GSTM1 and GSTT1 genotypes.
AB  - About 50% and 15% of Caucasians lack the glutathione S-transferase M1 (GSTM1) and
      T1 (GSTT1) genes and the corresponding enzyme activity, respectively. Both of
      these polymorphisms have been shown to affect the genotoxicity of some epoxides
      in cultured human lymphocytes. Especially GSTT1 appears to be important in whole
      blood cultures, probably because GSTT1 activity is high in erythrocytes. The in
      vitro genotoxicity of trans-stilbene oxide (TSO), a model substrate for GSTM1,
      has been shown to depend on individual GSTM1 activity. The potential role of
      GSTM1 genotype, and the possible interference of GSTT1 genotype, has not
      previously been examined in this context. We have studied TSO-induced sister
      chromatid exchanges (SCEs) in 72 h whole-blood lymphocyte cultures from 24
      healthy human donors, representing different combinations of GSTM1 and GSTT1
      positive and null genotypes. TSO clearly increased SCEs in cultures of all
      donors. The mean number of SCEs per cell induced by 75 and 150 microM TSO was,
      respectively, 1.5- and 1.3-times higher in cultures of GSTM1 null than GSTM1
      positive donors. In another experiment, GSTM1 null individuals showed, in
      comparison with GSTM1 positive subjects, a 1.8-fold SCE induction by 50 microM
      TSO. GSTT1 genotype did not have an unequivocal effect. Our findings suggest that
      the lack of the GSTM1 gene, resulting in reduced detoxification capacity,
      increases individual sensitivity to the genotoxic effects of TSO.

PMID- 11320156
TI  - Hydrogen peroxide: effects on DNA, chromosomes, cell cycle and apoptosis
      induction in Fanconi's anemia cell lines.
AB  - Fanconi's anemia (FA) is an inherited autosomal recessive syndrome; cells from FA
      patients are very sensitive to crosslinking agents and to oxygen. Epstein-Barr
      virus (EBV)-transformed lymphoblasts belonging to different FA complementation
      groups and normal EBV-transformed lymphoblasts were studied for their response to
      treatment with the oxidizing agent hydrogen peroxide (H2O2). The analysis of 8
      hydroxy-2'-deoxyguanosine (8-OHdG) content in the DNA of untreated cells showed
      an increased basal level of damage in cells from the complementation groups FA-C
      and FA-E. H2O2-induced 8-OHdG was higher in FA than in normal cell lines. The
      removal of 8-OHdG after H2O2 treatment was significantly reduced in the cells
      from complementation group E. However, all FA cell lines showed a normal ability
      in the resealing of DNA breaks, at least soon after treatment. All cell lines
      were also equally efficient in the removal of damaged pyrimidines. Compared with
      normal cells, FA cell lines showed an increase in the baseline level of
      micronuclei, but not in the number of micronuclei induced by H2O2. Micronuclei in
      FA cells originated prevalently from chromosomal fragmentation and, at a minor
      extent, from chromosome loss. After H2O2 treatment, FA cell lines accumulated in
      G(2) phase to a greater extent than normal lymphoblasts. However, reversion of
      mutation in FA-A and FA-C cells did not result in the correction of this
      phenotype. In cells evaluated for apoptosis no ladder formation was found in FA
      C, FA-E and corrected FA-C cells. In conclusion, among the FA cell lines
      examined, only FA-E showed a defect in the repair of H2O2-induced damage. On the
      other hand, differences found in the cell cycle and apoptosis might be due to
      irreversible changes occurring in FA cell lines as a consequence of the primary
      defect.

PMID- 11320157
TI  - Auditory peripersonal space in humans: a case of auditory-tactile extinction.
AB  - Animal experiments have shown that the spatial correspondence between auditory
      and tactile receptive fields of ventral pre-motor neurons provides a map of
      auditory peripersonal space around the head. This allows neurons to localize a
      near sound with respect to the head. In the present study, we demonstrated the
      existence of an auditory peripersonal space around the head in humans. In a right
      brain damaged patient with tactile extinction, a sound delivered near the
      ipsilesional side of the head extinguished a tactile stimulus delivered to the
      contralesional side of the head (cross-modal auditory-tactile extinction). In
      contrast, when an auditory stimulus was presented far from the head, cross-modal
      extinction was dramatically reduced. This spatially specific cross-modal
      extinction was found only when a complex sound like a white noise burst was
      presented; pure tones did not produce spatially specific cross-modal extinction.
      These results show a high degree of functional similarity between the
      characteristics of the auditory peripersonal space representation in humans and
      monkeys. This similarity suggests that analogous physiological substrates might
      be responsible for coding this multisensory integrated representation of
      peripersonal space in human and non-human primates.

PMID- 11320158
TI  - A double-blind placebo-controlled case study of the use of donepezil to improve
      cognition in a schizoaffective disorder patient: functional MRI correlates.
AB  - Cognitive impairment in multiple domains is common in patients with schizophrenia
      and may be a powerful determinant of poor functional ability and quality of life.
      We report a double-blind, placebo-controlled, cross-over study of donepezil
      augmentation in a schizoaffective disorder patient stabilized on olanzapine
      pharmacotherapy. The patient showed significant improvements in several cognitive
      measures and increased activation of prefrontal cortex and basal ganglia on
      functional MRI during the donepezil augmentation. In addition, the donepezil
      augmentation resulted in a reduction of depressive symptoms and in significant
      improvements in functional abilities and quality of life. Further studies of
      donepezil augmentation of neuroleptics in schizophrenia are warranted.

PMID- 11320159
TI  - The neuropsychology of frontal variant frontotemporal dementia and semantic
      dementia. Introduction to the special topic papers: Part II.
AB  - The second part of this review, which accompanies 10 special topic articles
      dedicated to frontotemporal dementia (FTD), describes some of the advances in
      understanding frontal variant FTD (fvFTD) and semantic dementia, and the
      theoretical insights gained into normal cognitive processes from the study of
      these syndromes. Recent work has clarified the neuropsychiatric features that
      distinguish fvFTD from Alzheimer's and has begun to spread light on the
      underlying deficits in social judgement, theory of mind, processing of emotional
      stimuli and decision making. With regard to central aspects of cognitive
      processing, such as memory, patients with fvFTD may have a distinctive profile of
      performance on tests of explicit and implicit memory, and contrary to current
      views some patients may even have a severe amnesic syndrome. There is also
      growing evidence that despite relatively well preserved general language skills,
      patients with fvFTD have particular problems with verb processing. Although there
      is agreement regarding the key features of semantic dementia, much controversy
      has surrounded the issue of whether the cognitive findings favour an explanation
      in terms of progressive breakdown of a central amodal semantic store or
      differential involvement of verbal and non-verbal systems. Other topics discussed
      include the impact of semantic breakdown on phonological processes and episodic
      memory. We also review recent structural and functional neuroimaging findings in
      semantic dementia.

PMID- 11320160
TI  - Dissociation of social cognition and executive function in frontal variant
      frontotemporal dementia.
AB  - In this paper, we adopt a neurodevelopmental stance to examining frontal variant
      frontotemporal dementia (fv-FTD) by using experimental procedures from the
      literature on the growth of social behaviour in children to examine the deficits
      in social reasoning which may underpin behavioural disturbance in fv-FTD. We
      present the case of a 47-year-old man with a diagnosis of fv-FTD and severe
      antisocial behaviour. Tests of general neuropsychology and of executive function
      were performed. In addition, the patient, JM, was assessed on tasks which test
      theory of mind. Theory of mind develops in distinct stages through childhood and
      is a core ability to represent the thoughts and feelings of others, independent
      of the level of intellectual ability. The results indicate relatively intact
      general neuropsychological and executive function, but extremely poor performance
      on tasks of theory of mind. This indicates a dissociation of social cognition and
      executive function suggesting that in psychiatric presentations of fv-FTD there
      may be a fundamental deficit in theory of mind independent of the level of
      executive function. The implications of this finding for diagnostic procedures
      and possible behavioural management are discussed.

PMID- 11320161
TI  - Novel applications of social-personality measures to the study of dementia.
AB  - Despite the realization that personality change is a core feature of
      frontotemporal dementia (FTD), little work has been performed using personality
      as a diagnostic tool for this disease. Likewise, personality change in
      Alzheimer's disease (AD) has long been recognized, but generally has not been
      used for diagnostic purposes. We introduce novel social-personality measures (Big
      Five Inventory, Interpersonal Adjectives Scale and Interpersonal Measure of
      Psychopathy) in the differential diagnosis of AD and temporal subtypes of FTD,
      and integrate these measures with traditional behavioural and neuropsychological
      methods commonly used in diagnosing dementia. We present four cases: an FTD
      patient with predominantly left temporal degeneration, an FTD patient with
      predominantly right temporal degeneration and two patients with Alzheimer's
      disease (one with mild and the other with moderate impairment). Results show the
      diagnostic utility of these measures in differentiating among temporal subtypes
      of FTD and moderate AD. Right temporal FTD, in particular, shows profound shifts
      in personality and interpersonal behaviour, as well as a striking lack of insight
      into these shifts. In addition to diagnostic purposes, we discuss how measures of
      personality and interpersonal behaviour can be utilized as an important component
      of understanding disease susceptibility and risk, as well as offering insights
      into the neuroanatomical underpinnings of personality and social behaviour.

PMID- 11320162
TI  - Hemispheric dominance for emotions, empathy and social behaviour: evidence from
      right and left handers with frontotemporal dementia.
AB  - Although evidence from primates suggests an important role for the anterior
      temporal cortex in social behaviour, human research has to date concentrated
      almost solely on the orbitofrontal cortex and amygdala. By describing four cases
      of the temporal variant of frontotemporal dementia we show how this degenerative
      condition provides an excellent model for investigating the role of the anterior
      temporal lobe, especially the right, in emotions, empathy and social behaviour.
      Assessments of semantic memory, processing of emotional facial expression and
      emotional prosody were made, empathy was measured, and facial expressions of
      emotion were coded. Of the two right handers described, one subject with
      predominantly left temporal lobe atrophy had severe semantic impairment but
      normal performance on all emotional tasks. In contrast, the subject with right
      temporal lobe atrophy showed severely impaired recognition of emotion from faces
      and voices that was not due to semantic or perceptual difficulties. Empathy was
      lost, interpersonal skills were severely affected and facial expression of
      emotion was characterized by a fixed expression that was unresponsive to
      situations. Additionally, two left handers with right temporal lobe atrophy are
      described. One demonstrated the same pattern of hemispheric lateralization as the
      right handers and had emotional impairment. The other left hander showed the
      opposite pattern of deficits, suggesting a novel presentation of anomalous
      dominance with reversed hemispheric specialization of semantic memory and
      emotional processing.

PMID- 11320163
TI  - Memory impairment differs in frontotemporal dementia and Alzheimer's disease.
AB  - The aim of this study was to assess short-term and long-term explicit memory and
      implicit memory in frontotemporal dementia (FTD; frontal variant) and to compare
      FTD and Alzheimer's disease (AD) patients with similar severity of dementia.
      Fifteen FTD patients [mean age: 68 years; Mini-Mental State (MMS): 24], 30
      probable AD patients (mean age: 72 years; MMS: 23) and 12 healthy subjects
      participated in the study. The three groups were comparable in terms of gender
      and educational level. Short-term memory was assessed with the digit span and
      Corsi block-tapping tests. Explicit verbal memory was assessed with the Grober
      and Buschke test, and implicit memory with a verbal priming task and a fragmented
      picture test. FTD patients demonstrated a genuine memory deficit with impaired
      digit span, encoding deficit and retrieval strategy difficulties, but preserved
      implicit verbal and visual priming. Memory patterns differed in AD and FTD: short
      term memory and free recall were similarly decreased in FTD and AD but cues
      provided more benefit to FTD than to AD; encoding was more impaired and the
      forgetting rate was faster in AD than in FTD; priming was lower in AD than in
      FTD. AD patients with clinical and imaging frontal lobe dysfunction tended to
      have lower memory performance and to differ even more from FTD patients than AD
      patients without frontal lobe dysfunction.

PMID- 11320164
TI  - Verb comprehension in frontotemporal degeneration: the role of grammatical,
      semantic and executive components.
AB  - Verb comprehension has been associated with the left frontal cortex, but
      assessments of verb comprehension in frontotemporal degeneration (FTD) have been
      rare. This study assessed word-picture matching for verbs and nouns under two
      conditions: alone (baseline) and during concurrent performance of a secondary
      task. In addition, we correlated FTD patients' verb comprehension with their
      performance on measures of executive resources and language. We found that FTD
      patients were significantly less accurate and required significantly longer to
      make word-picture matching decisions about verbs compared with nouns at baseline.
      During concurrent performance of a secondary task, accuracy decreased and
      response latencies became prolonged for nouns to the point that these measures
      equaled the performance with verbs at baseline. Verb comprehension accuracy was
      significantly correlated with the performance on executive measures such as
      category naming fluency, the Stroop test, and the Trail Making Test Part B
      (Trails B test). Assessment of FTD patient subgroups revealed distinct profiles
      of performance, suggesting that several factors contribute to verb comprehension
      in FTD. Verb comprehension in FTD patients with a dysexecutive syndrome (EXEC, n
      = 10) was sensitive to concurrent performance of a secondary task, and their verb
      comprehension accuracy correlated with the time required to complete executive
      measures such as the Stroop test and the Trails B test. This suggested a
      relationship between impaired verb comprehension and limited information
      processing speed in EXEC patients. Verb comprehension in patients with a
      progressive non-fluent aphasia (PNFA, n = 7) was not selectively influenced by
      executive resources. Instead, verb comprehension accuracy in PNFA was
      significantly correlated with sentence comprehension accuracy, suggesting that
      grammatical aspects of verbs play a crucial role in their verb comprehension
      difficulty. Although we studied only a small number of patients with semantic
      dementia (SD, n = 4), we observed significant verb comprehension difficulty that
      was minimally influenced by executive resources and was unrelated to sentence
      comprehension. It is possible that impaired verb comprehension in SD is related
      in part to the degradation of semantic feature knowledge.

PMID- 11320166
TI  - Noninvasive carotid imaging to select patients for endarterectomy: is it really
      safer than conventional angiography?

PMID- 11320167
TI  - Lawyers, litigation, and liability: can they make patients safer?

PMID- 11320168
TI  - Congenital muscular dystrophy: searching for a definition after 98 years.

PMID- 11320169
TI  - Practice advisory: participation of neurologists in direct-to-consumer
      advertising.

PMID- 11320170
TI  - Clinical carotid endarterectomy decision making: noninvasive vascular imaging
      versus angiography.
AB  - OBJECTIVE: Carotid endarterectomy (CEA) is frequently performed based solely on
      noninvasive vascular imaging (NVI) results (duplex ultrasound, DU; magnetic
      resonance angiography, MRA; CT angiography, CTA). The authors determined how
      often intra-arterial contrast angiography (ANGIO) alters a CEA decision as
      compared to NVI in clinical practice. METHODS: Reports of all NVI studies in 569
      consecutive patients undergoing ANGIO at an academic medical center (AMC, n =
      360) and a community hospital (CH, n = 209) over 3 years were reviewed. Patients
      were classified as to whether CEA was indicated based on each study.
      Misclassification rates, sensitivities, specificities, positive (PPV) and
      negative (NPV) predictive values were calculated. RESULTS: CTA was performed
      infrequently (2.5%) and not considered further. Misclassification rates for CEA
      based on DU in the AMC and CH were similar. The misclassification rate for DU
      alone was 28% (95% CI: 24,32), and for MRA alone was 18% (95% CI: 11,25). Both
      NVI were done in 11% of patients, with a misclassification rate of 7.9% (95% CI:
      0,16) when the two were concordant (76% of studies). DU had a sensitivity of 87%
      (95% CI: 83,91), specificity 46% (95% CI: 38,54), PPV 73% (95% CI: 68,78) and NPV
      68% (95% CI: 60,77). MRA had a sensitivity of 75% (95% CI: 63,87), specificity
      88% (95% CI: 80,96), PPV 84% (95% CI: 73,95) and NPV 80% (95% CI: 70, 90). The
      sensitivity of concordant NVIs was 96% (95% CI: 88,100), specificity 85% (95% CI:
      65,100), PPV 93% (95% CI: 81,100) and NPV 92% (95% CI: 76,100). CONCLUSION: These
      data suggest that surgical decisions should be made with caution if based on the
      results of noninvasive studies, particularly DU performed alone. Concordant DU
      and MRA results in a lower misclassification rate than either test used alone.

PMID- 11320171
TI  - Why are stroke patients excluded from TPA therapy? An analysis of patient
      eligibility.
AB  - BACKGROUND: Thrombolytic therapy for acute stroke (<3 hours) will not have a
      major impact on death and dependency unless it is accessible to more patients.
      OBJECTIVE: To determine why patients with ischemic stroke did not receive IV TPA
      and assess the availability of this therapy to patients with ischemic stroke.
      METHODS: Consecutive patients with acute ischemic stroke were prospectively
      identified at a university teaching hospital between October 1996 and December
      1999. Additional patients with ischemic stroke were identified that were admitted
      to one of three other hospitals in the Calgary region during the study period.
      The Oxford Community Stroke Programme Classification was used to record type and
      side of stroke. RESULTS: Of 2165 stroke patients presenting to the university
      hospital, 1168 (53.9%) were diagnosed with ischemic stroke, 31.8% with
      intracranial hemorrhage (intracerebral, subarachnoid, or subdural), and 13.9%
      with TIA. Delay in presentation to emergency department beyond 3 hours excluded
      73.1% (854/1168). Major reasons for delay included uncertain time of onset
      (24.2%), patients waited to see if symptoms would improve (29%), delay caused by
      transfer from an outlying hospital (8.9%), and inaccessibility of treating
      hospital (5.7%). Twenty-seven percent of patients with ischemic stroke (314/1168)
      were admitted within 3 hours of sympton onset and of these 84 (26.7%) patients
      received IV TPA. The major reasons for exclusion in this group of patients (<3
      hours) were mild stroke (13.1%), clinical improvement (18.2%), perceived protocol
      exclusions (13.6%), emergency department referral delay (8.9%), and significant
      comorbidity (8.3%). Of those patients who were considered too mild or were
      documented to have had significant improvement, 32% either remained dependent at
      hospital discharge or died during hospital admission. Throughout the region there
      was a total of 1806 ischemic stroke patients (admitted to all four Calgary
      hospitals). During this study period, 4.7% received IV TPA. CONCLUSIONS: The
      majority of patients are unable to receive TPA for acute ischemic stroke because
      they do no not reach the hospital soon enough. Of those patients presenting
      within 3 hours, 27% received the therapy but a further 31% were excluded because
      their symptoms were either considered too mild or were rapidly improving.
      Subsequently, a third of these patients were left either dependent or dead,
      bringing into question the initial decision not to treat.

PMID- 11320172
TI  - Dysarthria in acute ischemic stroke: lesion topography, clinicoradiologic
      correlation, and etiology.
AB  - BACKGROUND AND PURPOSE: Although dysarthria is a frequent symptom in cerebral
      ischemia, there is little information on its anatomic specificity, spectrum of
      associated clinical characteristics, and etiologic mechanisms. METHODS: An
      investigation of 68 consecutive patients with sudden onset of dysarthria due to a
      single infarction confirmed by MRI or CT was conducted. RESULTS: Dysarthria was
      associated with a classic lacunar stroke syndrome in 52.9% of patients. Isolated
      dysarthria and dysarthria-central facial and lingual paresis occurred in 2.9% (n
      = 2) and 10.3% (n = 7), respectively. Dysarthria-clumsy hand syndrome was
      observed in 11.7% (n = 8) of patients and associated with pure motor hemiparesis
      and/or ataxic hemiparesis in 27.9% (n = 19). The lesions were due to small-vessel
      disease in 52.9% (n = 36), to cardioembolism in 11.8% (n = 8), and to large
      vessel disease in only 4.4% (n = 3) of cases. Infarctions were located in the
      lower part of the primary motor cortex (5.9%; n = 4), middle part of the centrum
      semiovale (23.5%; n = 16), genu and ventral part of the dorsal segment of the
      internal capsule (8.8%; n = 6), cerebral peduncle (1.5%; n = 1), base of the pons
      (30.9%; n = 21), and ventral pontomedullary junction (1.5%; n = 1). Isolated
      cerebellar infarctions affected the rostral paravermal region in the superior
      cerebellar artery territory. CONCLUSIONS: Extracerebellar infarcts causing
      dysarthria were located in all patients along the course of the pyramidal tract.
      This finding correlates with the frequent occurrence of associated pyramidal
      tract signs in 90.7% (n = 62) of patients. Isolated cerebellar infarcts leading
      to dysarthria were in all cases located in the territory of the superior
      cerebellar artery.

PMID- 11320173
TI  - Involvement of the CACNA1A gene containing region on 19p13 in migraine with and
      without aura.
AB  - OBJECTIVE: To assess the involvement of the 19p13 familial hemiplegic migraine
      (FHM) locus in migraine with and without aura. BACKGROUND: Migraine with and
      without aura are likely to be polygenetic multifactorial disorders. FHM is a rare
      dominantly inherited type of migraine with aura. In about 50% of families, FHM is
      caused by mutations in the P/Q-type calcium channel alpha(1A)-subunit (CACNA1A)
      gene on chromosome 19p13. The CACNA1A gene is thus a good candidate gene for
      "nonhemiplegic" migraine with or without aura. METHODS: The authors performed an
      affected sibpair analysis using flanking and CACNA1A intragenic markers. The
      authors assessed the occurrence of shared parental marker alleles among 189
      affected siblings from 36 extended families with typical migraine with or without
      aura. RESULTS: Sibling pairs with any form of migraine had inherited the same
      19p13 CACNA1A-containing region significantly more frequently than expected by
      chance (maximum multipoint lod score = 1.22). This result was almost exclusively
      dependent on the increased sharing found in sibling pairs with migraine with aura
      (maximum multipoint lod score = 1.41). The locus-specific relative risk for a
      sibling (lambda(s)) to suffer from migraine with aura, defined as the increase in
      risk of the trait attributable to the 19p13 locus, was lambda(s) = 1.56. When
      combining migraine with and without aura, lambda(s) was 1.22. CONCLUSIONS: The
      increased allele sharing in the CACNA1A gene region on 19p13 is consistent with
      an important involvement of this region in migraine, especially migraine with
      aura.

PMID- 11320174
TI  - Characterization of chronic daily headaches in children in a multidisciplinary
      headache center.
AB  - BACKGROUND: Chronic daily headaches (CDH) occur in >4% of the adult population.
      The criteria for CDH, however, are controversial. In children, the
      characterization of frequent headaches and CDH is limited. METHODS: A Headache
      Center to characterize headaches in children (3 to 18 years old) was established.
      Over 34 months, 577 children have been evaluated. With use of a definition of >
      or =15 headaches per month, 200 (34.6%) children had CDH. RESULTS: The average
      age at the first headache in these children was 9.3 +/- 3.6 years, whereas the
      average age at presentation to the Headache Center was 12.5 +/- 3.1 years. Sixty
      eight percent were girls, 88% were Caucasian, and 11% were African American.
      Ninety-two percent clinically had migraine headaches, whereas 60.5% met the
      International Headache Society migraine criteria. The pain was pulsatile in 79%,
      63.5% had nausea with or without vomiting, and 59.5% had photophobia and
      phonophobia. Three subcategories emerged, with 37% having frequent headaches but
      not daily, 43.5% having episodic daily headaches, and 19.5% having a continuous
      headache. CONCLUSION: The features of CDH in children most closely match those of
      migraine. A clear division of these children using frequency identifies three
      groups: frequent headaches (15 to 29), daily intermittent, and daily continuous.
      The daily continuous group is the most unique; however, the nature of these
      headaches continues to remain migrainous.

PMID- 11320175
TI  - Neuromuscular transmission in migraine: a single-fiber EMG study in clinical
      subgroups.
AB  - OBJECTIVE: To search for impairment of neuromuscular transmission by single-fiber
      electromyography (SFEMG) in patients with common forms of migraine. BACKGROUND:
      P/Q Ca(2+) channels are genetically abnormal in most cases of familial hemiplegic
      migraine (International Headache Society [IHS] code 1.2.3) and may be involved in
      other types of migraine. Besides in the brain, these channels are found in motor
      nerve endings, where they control stimulation-induced acetylcholine release. If
      they are functionally abnormal, the neuromuscular transmission might be impaired.
      METHODS: Sixty-two migraineurs (18 without aura, IHS code 1.1; 19 with typical
      aura, IHS code 1.2.1; 10 with prolonged aura, IHS code 1.2.2; 15 with and without
      aura) and 16 healthy control subjects underwent stimulation SFEMG. Results were
      expressed as the mean value of consecutive differences (MCD) and percentage of
      single-fiber abnormalities (abnormal jitter or impulse blocking). RESULTS:
      Average MCD was comparable in control subjects and migraineurs (17.1 +/- 2.6
      versus 17.5 +/- 4.7 microsec). By contrast, single-fiber abnormalities were found
      in 17 patients but in none of the control subjects (p = 0.036). Most of these
      patients had unilateral sensorimotor symptoms and/or aphasia and/or loss of
      balance during the aura. SFEMG abnormalities were significantly correlated with
      the occurrence of these clinical features and with a diagnosis of migraine with
      prolonged aura. CONCLUSIONS: Stimulation SFEMG shows mild abnormalities of
      neuromuscular transmission in a subgroup of migraineurs with aura, characterized
      by clinical features frequently found in human P/Q Ca(2+) channelopathies. These
      abnormalities might thus be due to genetically modified P/Q Ca(2+) channels.

PMID- 11320176
TI  - Relationship of extinction to perceptual thresholds for single stimuli.
AB  - OBJECTIVE: To demonstrate the effects of target stimulus intensity on extinction
      to double simultaneous stimuli. BACKGROUND: Attentional deficits contribute to
      extinction in patients with brain lesions, but extinction (i.e., masking) can
      also be produced in healthy subjects. The relationship of extinction to
      perceptual thresholds for single stimuli remains uncertain. METHODS: Brief
      electrical pulses were applied simultaneously to the left and right index fingers
      of 16 healthy volunteers (8 young and 8 elderly adults) and 4 patients with right
      brain stroke (RBS). The stimulus to be perceived (i.e., target stimulus) was
      given at the lowest perceptual threshold to perceive any single stimulus (i.e.,
      Minimal) and at the threshold to perceive 100% of single stimuli. The mask
      stimulus (i.e., stimulus given to block the target) was applied to the
      contralateral hand at intensities just below discomfort. RESULTS: Extinction was
      less for target stimuli at 100% than Minimal threshold for healthy subjects.
      Extinction of left targets was greater in patients with RBS than elderly control
      subjects. Left targets were extinguished less than right in healthy subjects. In
      contrast, the majority of left targets were extinguished in patients with RBS
      even when right mask intensity was reduced below right 100% threshold for single
      stimuli. RBS patients had less extinction for right targets despite having
      greater left mask - threshold difference than control subjects. In patients with
      RBS, right "targets" at 100% threshold extinguished left "masks" (20%) almost as
      frequently as left masks extinguished right targets (32%). CONCLUSIONS: Subtle
      changes in target intensity affect extinction in healthy adults. Asymmetries in
      mask and target intensities (relative to single-stimulus perceptual thresholds)
      affect extinction in RBS patients less for left targets but more for right
      targets as compared with control subjects.

PMID- 11320177
TI  - Neuropsychological assessment in children with absence epilepsy.
AB  - OBJECTIVE: To define cognitive deficits in children with absence epilepsy.
      BACKGROUND: Cognitive deficits have often been reported in children with
      epilepsy, but have rarely been characterized in patients with a specific
      epileptic syndrome. METHODS: Detailed neuropsychological testing was carried out
      on 16 right-handed children with absence epilepsy with similar clinical and EEG
      findings, and the findings were compared to 16 well-matched right-handed children
      without absence epilepsy. RESULTS: The authors found lower scores of measures of
      general cognitive functioning and visuospatial skills in patients with absence
      epilepsy, as compared to controls. Memory disturbances were also detected in
      absence epilepsy patients, with selective involvement of nonverbal memory and
      delayed recall. In contrast, verbal memory and language skills were relatively
      preserved. Patients whose seizures began at an earlier age seemed to have more
      severe cognitive deficits. CONCLUSION: Language skills tend to be relatively well
      preserved in children with generalized epilepsy, with more dysfunction seen in
      global terms rather than specific lateralizing deficits. Patients with absence
      epilepsy seem to show a similar neurocognitive profile that may be a reflection
      of the underlying epilepsy syndrome.

PMID- 11320178
TI  - Retest effects and cognitive decline in longitudinal follow-up of patients with
      early HD.
AB  - OBJECTIVE: To assess the natural progression of cognitive impairment in
      Huntington's disease (HD) and to reveal factors that may mask this progression.
      BACKGROUND: Although numerous cross-sectional studies reported cognitive
      deterioration at different stages of the disease, progressive cognitive
      deterioration has been, up to now, difficult to demonstrate in neuropsychological
      longitudinal studies. METHODS: The authors assessed 22 patients in early stages
      of HD at yearly intervals for 2 to 4 years (average, 31.2 +/- 10 months), using a
      comprehensive neuropsychological battery based on the Core Assessment Program for
      Intracerebral Transplantation in Huntington's Disease (CAPIT-HD). RESULTS: The
      authors observed a significant decline in different cognitive functions over
      time: these involved primarily attention and executive functions but also
      involved language comprehension, and visuospatial immediate memory. Episodic
      memory impairment that was already present at the time of enrollment did not show
      significant decline. The authors found a significant retest effect at the second
      assessment in many tasks. CONCLUSION: Many attention and executive tasks
      adequately assess the progression of the disease at an early stage. For other
      functions, the overlapping of retest effects and disease progression may confuse
      the results. High interindividual and intraindividual variability seem to be
      hallmarks of the disease.

PMID- 11320179
TI  - Clinical and genetic distinction between Walker-Warburg syndrome and muscle-eye
      brain disease.
AB  - BACKGROUND: Three rare autosomal recessive disorders share the combination of
      congenital muscular dystrophy and brain malformations including a neuronal
      migration defect: muscle-eye-brain disease (MEB), Walker-Warburg syndrome (WWS),
      and Fukuyama congenital muscular dystrophy (FCMD). In addition, ocular
      abnormalities are a constant feature in MEB and WWS. Lack of consistent ocular
      abnormalities in FCMD has allowed a clear clinical demarcation of this syndrome,
      whereas the phenotypic distinction between MEB and WWS has remained
      controversial. The MEB gene is located on chromosome 1p32-p34. OBJECTIVES: To
      establish distinguishing diagnostic criteria for MEB and WWS and to determine
      whether MEB and WWS are allelic disorders. METHODS: The authors undertook
      clinical characterization followed by linkage analysis in 19 MEB/WWS families
      with 29 affected individuals. With use of clinical diagnostic criteria based on
      Finnish patients with MEB, each patient was categorized as having either MEB or
      WWS. A linkage and haplotype analysis using 10 markers spanning the MEB locus was
      performed on the entire family resource. RESULTS: Patients in 11 families were
      classified as having MEB and in 8 families as WWS. Strong evidence in favor of
      genetic heterogeneity was obtained in the 19 families. There was evidence for
      linkage to 1p32-p34 in all but 1 of the 11 pedigrees segregating the MEB
      phenotype. In contrast, linkage to the MEB locus was excluded in seven of eight
      of the WWS families. CONCLUSION: These results allow the classification of MEB
      and WWS as distinct disorders on both clinical and genetic grounds and provide a
      basis for the mapping of the WWS gene(s).

PMID- 11320180
TI  - Lack of apoptosis in mitochondrial encephalomyopathies.
AB  - BACKGROUND/OBJECTIVE: Apoptosis, or programmed cell death, is an evolutionary
      conserved mechanism essential for morphogenesis and tissue homeostasis, but it
      plays an important role also in pathologic conditions, including neurologic
      disorders. Its execution pathway is critically regulated at the mitochondrial
      level. Evidence of apoptosis in muscle specimens was investigated in patients
      with genetically defined mitochondrial encephalomyopathies. METHODS: Thirty-three
      muscle biopsies from patients with genotypically different mitochondrial diseases
      (single and multiple deletions, A3243G/A8344G point mutations of the
      mitochondrial DNA) were studied. The terminal deoxynucleotidyl transferase
      mediated dUTP nick end labeling (TUNEL) reaction was used as a marker of nuclear
      DNA fragmentation, as well as antibodies against pro- (Fas) or anti- (Bcl-2)
      apoptotic factors. Also, because one hallmark of apoptosis is morphologic,
      ultrastructural studies were performed on skeletal muscle from 18 of 33 patients,
      examining both phenotypically normal and ragged red fibers. RESULTS: In all
      muscle biopsies, no significant expression of either pro (Fas) and inhibiting
      (Bcl-2) apoptosis-related proteins was found, nor TUNEL positivity. This latter
      finding is confirmed by lack of morphologic evidence of apoptosis in all the
      fibers examined at the ultrastructural level. CONCLUSION: The authors' findings
      suggest that genetically determined defects of oxidative phosphorylation do not
      induce the apoptotic process and that apoptosis is not involved in the
      pathogenesis of mitochondrial disorders.

PMID- 11320181
TI  - A randomized efficacy and safety trial of oxandrolone in the treatment of
      Duchenne dystrophy.
AB  - BACKGROUND: A pilot study suggested that oxandrolone, an anabolic steroid,
      improved strength in boys with Duchenne dystrophy (DD) and indicated the need for
      a more definitive study. METHODS: A 6-month, randomized, double-blind, placebo
      controlled study of oxandrolone in boys with an established diagnosis of DD,
      using the change from baseline to 6 months in the average muscle strength score
      (MMT) as the primary efficacy measure. RESULTS: The mean change from baseline for
      the oxandrolone group was +0.035 and that for the placebo group was -0.140.
      Although the oxandrolone group did not get worse and the placebo patients showed
      some deterioration in strength, the difference was not significant (p = 0.13).
      The average of the four quantitative muscle tests (QMT) showed a significant
      improvement in the oxandrolone-treated boys as compared with placebo. No adverse
      reactions attributable to oxandrolone were recorded. CONCLUSIONS: Although
      oxandrolone did not produce a significant change in the average manual muscle
      strength score as compared with placebo, the mean change in QMT was significant.
      Because oxandrolone is safe, accelerates linear growth, and may have some
      beneficial effect in slowing the progress of weakness, it may be useful before
      initiating corticosteroid therapy.

PMID- 11320182
TI  - Creutzfeldt-Jakob disease after receipt of a previously unimplicated brand of
      dura mater graft.
AB  - BACKGROUND: Iatrogenic Creutzfeldt-Jakob disease (CJD) transmission via dura
      mater grafts has been reported in many countries. In September 1998, a 39-year
      old Colorado woman was reported as having suspected CJD after receiving a dura
      mater graft 6 years earlier. METHODS: An investigation was initiated to confirm
      the diagnosis of CJD and assess the possible source of CJD transmission. The
      authors determined the presence or absence of other known CJD risk factors,
      checked for epidemiologic evidence of possible CJD transmission via neurosurgical
      instruments, and evaluated the procedures used in the collection and processing
      of the graft, including whether the donor may have had CJD. RESULTS: The CJD
      diagnosis was confirmed in the dural graft recipient by neuropathologic and
      immunodiagnostic evaluation of the autopsy brain tissue. She had no history of
      receipt of cadaveric pituitary hormones or corneal grafts or of CJD in her
      family. The authors found no patients who underwent a neurosurgical procedure
      within 6 months before or 5 months after the patient's surgery in 1992 who had
      been diagnosed with CJD. The dura mater was obtained from a 57-year-old man with
      a history of dysarthria, ataxia, and behavioral changes of uncertain origin. The
      graft was commercially prepared by use of a process that included treatment with
      0.1 N sodium hydroxide and avoided commingling of dura from different donors.
      CONCLUSIONS: The patient's age, absence of evidence for other sources of CJD, the
      latent period, and the report of an unexplained neurologic illness in the donor
      of the dura mater indicate that the graft was the most likely source of CJD in
      this patient.

PMID- 11320183
TI  - MRI and CSF oligoclonal bands after autologous hematopoietic stem cell
      transplantation in MS.
AB  - OBJECTIVE: To analyze the MRI and CSF oligoclonal bands (OB) changes in patients
      with MS who underwent an autologous hematopoietic stem cell transplantation
      (AHSCT). BACKGROUND: AHSCT is evaluated as an alternative therapy in severe MS.
      In previous series of AHSCT for MS, data on MRI or OB outcome were limited or not
      provided. METHODS: Five patients with a median Kurtzke's EDSS score of 6.5, more
      than two attacks, and confirmed worsening of the EDSS in the previous year
      received an AHSCT. Hematopoietic stem cells were mobilized with cyclophosphamide
      (3 g/m2) and granulocyte colony-stimulating factor (5 microg/kg/d). The graft was
      T cell depleted by positive CD 34+ selection. Conditioning regimen included BCNU
      (300 mg/m(2)), cyclophosphamide (150 mg/kg in 3 days), and antithymocyte globulin
      (60 mg/kg in 4 days). MRI scans were scheduled at baseline and 1, 3, 6, and 12
      months and OB analysis at baseline and 3 and 12 months post-AHSCT. RESULTS: Four
      patients had a stable or improved EDSS after a median follow-up of 18 months
      (range, 12 to 24 months). The fifth patient's condition deteriorated during
      AHSCT. She partially improved and remained stable after month 3 after AHSCT. The
      baseline CSF OB persisted 1 year after AHSCT. MRI studies after AHSCT showed no
      enhanced T1 lesions and no new or enlarging T2 lesions. The median percentage
      change of T2 lesion load was -11.8% (range, -26.6 to -4.0%). All patients had a
      decrease of corpus callosum area at 1 year (median, 12.4%; range, 7.8% to 20.5%)
      that did not progress in the two patients evaluated at 2 years after AHSCT.
      CONCLUSIONS: Although the persistence of CSF OB suggests the lymphocytes were not
      eliminated from the CNS, the follow-up MRI studies showed no enhanced T1 brain
      lesions and a reduction in the T2 lesion load that correlated with the clinical
      stabilization of MS after AHSCT.

PMID- 11320184
TI  - The influence of cognitive impairment on driving performance in multiple
      sclerosis.
AB  - OBJECTIVE: To examine the influence of impaired cognitive processing on measures
      of driving skills in persons with MS. METHODS: Twenty-eight subjects with
      documented MS were divided into two groups-with [MS(+), n = 13] and without [MS(
      ), n = 15] cognitive impairment-based on neuropsychological performance. Healthy
      control (HC) subjects (n = 17) matched on age and driving experience were also
      studied. Driving-related skills were compared between the groups based on
      performance on two computerized driving tests: the Useful Field of Vision (UFOV)
      and the Neurocognitive Driving Test (NDT). RESULTS: The MS(+) group performed
      significantly worse than both the MS(-) and HC groups in the latency to perform
      several driving-specific functions on the NDT, but no overall group differences
      were observed in actual errors on the NDT. On the UFOV, when compared to MS(-)
      and HC subjects, the MS(+) group demonstrated poorer performance on two of the
      three subtests. Additionally, a significantly higher percentage of MS(+)
      individuals were rated within the high risk (probability of crash involvement)
      category, relative to the MS(-) and HC groups. CONCLUSIONS: Cognitive impairment
      can negatively affect driving-related skills in persons with MS and should be
      considered in the determination of driving ability.

PMID- 11320185
TI  - Increased CSF cortisol in AD is a function of APOE genotype.
AB  - BACKGROUND: Increased hypothalamic-pituitary-adrenal (HPA) axis activity
      manifested by elevated cortisol levels is observed in AD and may contribute to AD
      by lowering the threshold for neuronal degeneration. Presence of the APOE
      epsilon4 allele increases risk for AD. Increased cortisol concentrations in apoE
      deficient mice suggest that APOE genotype may influence cortisol concentrations
      in AD. METHODS: The authors measured cortisol levels in CSF and determined APOE
      genotypes for 64 subjects with AD and 34 nondemented older control subjects.
      RESULTS: CSF cortisol was significantly higher in AD than in control subjects.
      CSF cortisol concentrations differed with respect to APOE genotype in both
      subjects with AD (epsilon4/epsilon4 > epsilon3/4epsilon > epsilon3/epsilon3) and
      normal older control subjects (epsilon3/epsilon4 > epsilon3/epsilon3 >
      epsilon2/epsilon3). Comparison of CSF cortisol concentrations within the
      epsilon3/epsilon4 and epsilon3/epsilon3 genotypes revealed no differences between
      AD and control subject groups. CONCLUSIONS: Higher CSF cortisol concentrations
      were associated with increased frequency of the APOE-epsilon4 allele and
      decreased frequency of the APOE-epsilon2 allele in AD subjects relative to
      control subjects. This effect of APOE genotype on HPA axis activity may be
      related to the increased risk for AD in persons carrying the APOE-epsilon4 allele
      and decreased risk for AD in persons carrying the APOE-epsilon2 allele.

PMID- 11320186
TI  - Malpractice claims: outcome evidence to guide neurologic education?
AB  - The choice of objectives and content in neurologic education should be informed
      by evidence from patient outcomes and errors. Malpractice claims are proposed as
      one data source, although they only partially reflect health outcomes.
      Epidemiologic, statewide data suggest some provisional priorities for key topics
      and training targets, but require further research to assess their value for
      guiding neurologic education.

PMID- 11320187
TI  - No correlation between muscle A3243G mutation load and mitochondrial function in
      vivo.
AB  - The authors studied the relationship between the percentage level of A3243G
      mitochondrial DNA mutation and the degree of mitochondrial dysfunction in vivo in
      nine individuals from four pedigrees using phosphorus MRS in muscle. There was no
      significant correlation between mutation load and maximum rate of adenosine
      triphosphate production (V(max)). V(max) was normal in a subject with 32% A3243G
      in muscle, which is in contrast with a previous observation of markedly reduced
      V(max) in a patient with only 6% A3243G in muscle. Factors besides mutation load,
      such as nuclear genes, influence expression of the A3243G mutation in vivo.

PMID- 11320188
TI  - Clinical features and prognosis of Miller Fisher syndrome.
AB  - The authors reviewed the clinical features and outcome of Miller Fisher syndrome
      (MFS) for 50 consecutive patients with MFS including 28 patients who received no
      immunotherapy. Besides the characteristic clinical triad (ophthalmoplegia,
      ataxia, and areflexia), pupillary abnormalities, blepharoptosis, and facial palsy
      are frequent in MFS, whereas sensory loss is unusual despite the presence of
      profound ataxia. Patients with MFS usually had good recovery and no residual
      deficits.

PMID- 11320190
TI  - Poor school and cognitive functioning with silent cerebral infarcts and sickle
      cell disease.
AB  - The authors evaluated education attainment and neuropsychological deficits in
      children with sickle cell disease (SCD) and silent cerebral infarcts. Children
      with silent infarcts had twice the rate of school difficulties as children
      without infarcts. Eighty percent of silent infarct cases had clinically
      significant cognitive deficits, whereas 35% had deficits in academic skills.
      Children with silent cerebral infarcts show high rates of poor educational
      attainment, cognitive deficits, and frontal lobe injury. Poor school performance
      in SCD is one indicator of silent infarcts.

PMID- 11320189
TI  - Cerebral involvement in graft-versus-host disease after murine bone marrow
      transplantation.
AB  - Neurologic manifestation of graft-versus-host disease (GvHD) after allogeneic
      bone marrow transplantation (BMT) has until now been limited to rare
      neuromuscular syndromes. Investigating cerebral findings using a murine BMT
      model, the authors found parenchymal lymphocytic inflammation, microglia
      activation, and mild cerebral angiitis-like changes in allogeneic transplanted
      animals but not in syngeneic controls. These findings suggest that cerebral
      involvement during GvHD may be a new neurologic complication after BMT.

PMID- 11320191
TI  - Safety of Diastat when given at larger-than-recommended doses for acute
      repetitive seizures.

PMID- 11320192
TI  - Cerebral sinus thrombosis with tamoxifen.

PMID- 11320193
TI  - Adult-onset combined methylmalonic aciduria and homocystinuria (cblC).

PMID- 11320194
TI  - Herpes simplex virus encephalitis complicating myxedema coma treated with
      corticosteroids.

PMID- 11320195
TI  - Episodic encephalopathy with dilated pupils.

PMID- 11320196
TI  - Pseudomeningoceles: a role for mechanical compression in the treatment of dural
      tears.

PMID- 11320197
TI  - Carotid endarterectomy: another wake-up call.

PMID- 11320198
TI  - A compulsive collecting behavior following an A-com aneurysmal rupture.

PMID- 11320199
TI  - Results of carotid endarterectomy with prospective neurologist follow-up.

PMID- 11320200
TI  - Pharmacologic treatment of pain in polyneuropathy.

PMID- 11320201
TI  - Paraspinal motor evoked potentials by magnetic stimulation of the motor cortex.

PMID- 11320202
TI  - Apoptotic features accompany acute quadriplegic myopathy.

PMID- 11320205
TI  - The role of distinct p185neu extracellular subdomains for dimerization with the
      epidermal growth factor (EGF) receptor and EGF-mediated signaling.
AB  - The extracellular domain of p185(c-neu) can be viewed as a complex structure of
      four subdomains, two of which are cysteine-rich subdomains. We have investigated
      the contribution of these distinct p185(c-neu) extracellular subdomains to
      p185/epidermal growth factor receptor (EGFR) heteromer formation and EGF-induced
      heteromeric signaling. Our studies indicate that at least two separate p185
      subdomains, a region spanning subdomains I and II and subdomain IV are involved
      in association of p185 with the EGFR. We also demonstrated that subdomain IV
      reduced the heteromeric signaling and transforming activities induced by EGF
      after associating with EGFR. When 126 aa were deleted from subdomain IV, this
      small subdomain IV-derived fragment could still lead to heterodimers with EGFR
      and suppress EGF-induced mitogen-activated protein kinase activation and
      subsequent transformation abilities. These data provide information about trans
      inhibitory mechanisms of mutant p185 species and also indicate that both the
      entire and a part of subdomain IV may represent a therapeutic target for erbB
      overexpressing tumors. Finally, these studies define a basic feature of receptor
      receptor associations that are determined by cystine-knot containing subdomains.

PMID- 11320206
TI  - Methionine adenosyltransferase 1A knockout mice are predisposed to liver injury
      and exhibit increased expression of genes involved in proliferation.
AB  - Liver-specific and nonliver-specific methionine adenosyltransferases (MATs) are
      products of two genes, MAT1A and MAT2A, respectively, that catalyze the formation
      of S-adenosylmethionine (AdoMet), the principal biological methyl donor. Mature
      liver expresses MAT1A, whereas MAT2A is expressed in extrahepatic tissues and is
      induced during liver growth and dedifferentiation. To examine the influence of
      MAT1A on hepatic growth, we studied the effects of a targeted disruption of the
      murine MAT1A gene. MAT1A mRNA and protein levels were absent in homozygous
      knockout mice. At 3 months, plasma methionine level increased 776% in knockouts.
      Hepatic AdoMet and glutathione levels were reduced by 74 and 40%, respectively,
      whereas S-adenosylhomocysteine, methylthioadenosine, and global DNA methylation
      were unchanged. The body weight of 3-month-old knockout mice was unchanged from
      wild-type littermates, but the liver weight was increased 40%. The Affymetrix
      genechip system and Northern and Western blot analyses were used to analyze
      differential expression of genes. The expression of many acute phase-response and
      inflammatory markers, including orosomucoid, amyloid, metallothionein, Fas
      antigen, and growth-related genes, including early growth response 1 and
      proliferating cell nuclear antigen, is increased in the knockout animal. At 3
      months, knockout mice are more susceptible to choline-deficient diet-induced
      fatty liver. At 8 months, knockout mice developed spontaneous macrovesicular
      steatosis and predominantly periportal mononuclear cell infiltration. Thus,
      absence of MAT1A resulted in a liver that is more susceptible to injury,
      expresses markers of an acute phase response, and displays increased
      proliferation.

PMID- 11320207
TI  - BRS1, a serine carboxypeptidase, regulates BRI1 signaling in Arabidopsis
      thaliana.
AB  - Brassinosteroid-insensitive 1 (BRI1) of Arabidopsis thaliana encodes a cell
      surface receptor for brassinosteroids. Mutations in BRI1 severely affect plant
      growth and development. Activation tagging of a weak bri1 allele (bri1-5)
      resulted in the identification of a new locus, brs1-1D. BRS1 is predicted to
      encode a secreted carboxypeptidase. Whereas a brs1 loss-of-function allele has no
      obvious mutant phenotype, overexpression of BRS1 can suppress bri1 extracellular
      domain mutants. Genetic analyses showed that brassinosteroids and a functional
      BRI1 protein kinase domain are required for suppression. In addition,
      overexpressed BRS1 missense mutants, predicted to abolish BRS1 protease activity,
      failed to suppress bri1-5. Finally, the effects of BRS1 are selective:
      overexpression in either wild-type or two other receptor kinase mutants resulted
      in no phenotypic alterations. These results strongly suggest that BRS1 processes
      a protein involved in an early event in the BRI1 signaling.

PMID- 11320208
TI  - Transferring an inborn auditory perceptual predisposition with interspecies brain
      transplants.
AB  - Inborn species' perceptual preferences are thought to serve as important guides
      for neonatal learning in most species of higher vertebrates. Although much work
      has been carried out on experiential contributions to the expression of such
      preferences, their neural and developmental correlates remain largely unexplored.
      Here we use embryonic neural transplants between two bird species, the Japanese
      quail and the domestic chicken, to demonstrate that an inborn auditory perceptual
      predisposition is transferable between species. The transfer of the perceptual
      preference was dissociated from changes to the vocalizations of the resulting
      animals (called chimeras), suggesting that experiential differences in auditory
      self-stimulation cannot explain the perceptual change. A preliminary localization
      of the effective brain region for the behavioral transfer by using a naturally
      occurring species-cell marker revealed that it is not contained within the major
      avian auditory pathways. To our knowledge, this is the first demonstration that
      abstract aspects of auditory perception can be transferred between species with
      transplants of the central nervous system.

PMID- 11320209
TI  - Sequence conservation at human and mouse orthologous common fragile regions,
      FRA3B/FHIT and Fra14A2/Fhit.
AB  - It has been suggested that delayed DNA replication underlies fragility at common
      human fragile sites, but specific sequences responsible for expression of these
      inducible fragile sites have not been identified. One approach to identify such
      cis-acting sequences within the large nonexonic regions of fragile sites would be
      to identify conserved functional elements within orthologous fragile sites by
      interspecies sequence comparison. This study describes a comparison of
      orthologous fragile regions, the human FRA3B/FHIT and the murine Fra14A2/Fhit
      locus. We sequenced over 600 kbp of the mouse Fra14A2, covering the region
      orthologous to the fragile epicenter of FRA3B, and determined the Fhit deletion
      break points in a mouse kidney cancer cell line (RENCA). The murine Fra14A2
      locus, like the human FRA3B, was characterized by a high AT content. Alignment of
      the two sequences showed that this fragile region was stable in evolution despite
      its susceptibility to mitotic recombination on inhibition of DNA replication.
      There were also several unusual highly conserved regions (HCRs). The positions of
      predicted matrix attachment regions (MARs), possibly related to replication
      origins, were not conserved. Of known fragile region landmarks, five cancer cell
      break points, one viral integration site, and one aphidicolin break cluster were
      located within or near HCRs. Thus, comparison of orthologous fragile regions has
      identified highly conserved sequences with possible functional roles in
      maintenance of fragility.

PMID- 11320210
TI  - The P450-1 gene of Gibberella fujikuroi encodes a multifunctional enzyme in
      gibberellin biosynthesis.
AB  - Recent studies have shown that the genes of the gibberellin (GA) biosynthesis
      pathway in the fungus Gibberella fujikuroi are organized in a cluster of at least
      seven genes. P450-1 is one of four cytochrome P450 monooxygenase genes in this
      cluster. Disruption of the P450-1 gene in the GA-producing wild-type strain IMI
      58289 led to total loss of GA production. Analysis of the P450-1-disrupted
      mutants indicated that GA biosynthesis was blocked immediately after ent
      kaurenoic acid. The function of the P450-1 gene product was investigated further
      by inserting the gene into mutants of G. fujikuroi that lack the entire GA gene
      cluster; the gene was highly expressed under GA production conditions in the
      absence of the other GA-biosynthesis genes. Cultures of transformants containing
      P450-1 converted ent-[(14)C]kaurenoic acid efficiently into [(14)C]GA(14),
      indicating that P450-1 catalyzes four sequential steps in the GA-biosynthetic
      pathway: 7beta-hydroxylation, contraction of ring B by oxidation at C-6, 3beta
      hydroxylation, and oxidation at C-7. The GA precursors ent-7alpha
      hydroxy[(14)C]kaurenoic acid, [(14)C]GA(12)-aldehyde, and [(14)C]GA(12) were also
      converted to [(14)C]GA(14). In addition, there is an indication that P450-1 may
      also be involved in the formation of the kaurenolides and fujenoic acids, which
      are by-products of GA biosynthesis in G. fujikuroi. Thus, P450-1 displays
      remarkable multifunctionality and may be responsible for the formation of 12
      products.

PMID- 11320211
TI  - Virulence of a Mycobacterium tuberculosis clinical isolate in mice is determined
      by failure to induce Th1 type immunity and is associated with induction of IFN
      alpha /beta.
AB  - To understand how virulent mycobacteria subvert host immunity and establish
      disease, we examined the differential response of mice to infection with various
      human outbreak Mycobacterium tuberculosis clinical isolates. One clinical
      isolate, HN878, was found to be hypervirulent, as demonstrated by unusually early
      death of infected immune-competent mice, compared with infection with other
      clinical isolates. The differential effect on survival required lymphocyte
      function because severe combined immunodeficiency (SCID) mice infected with HN878
      or other clinical isolates all died at the same rate. The hypervirulence of HN878
      was associated with failure to induce M. tuberculosis-specific proliferation and
      IFN-gamma production by spleen and lymph node cells from infected mice. In
      addition, 2- to 4-fold lower levels of tumor necrosis factor-alpha (TNF-alpha),
      IL-6, IL-12, and IFN-gamma mRNAs were observed in lungs of HN878-infected mice.
      IL-10, IL-4, and IL-5 mRNA levels were not significantly elevated in lungs of
      HN878 infected mice. In contrast, IFN-alpha mRNA levels were significantly higher
      in lungs of these mice. To further investigate the role of Type 1 IFNs, mice
      infected with HN878 were treated intranasally with purified IFN-alpha/beta. The
      treatment resulted in increased lung bacillary loads and even further reduced
      survival. These results suggest that the hypervirulence of HN878 may be due to
      failure of this strain to stimulate Th1 type immunity. In addition, the lack of
      development of Th1 immunity in response to HN878 appears to be associated with
      increased induction of Type 1 IFNs.

PMID- 11320212
TI  - Surface expression and function of p75/AIRM-1 or CD33 in acute myeloid leukemias:
      engagement of CD33 induces apoptosis of leukemic cells.
AB  - p75/AIRM-1 is a recently identified inhibitory receptor expressed by natural
      killer and myeloid cells displaying high homology with CD33. Crosslinking of
      p75/AIRM-1 or CD33 has been shown to sharply inhibit the in vitro proliferation
      of both normal myeloid cells and chronic myeloid leukemias. In this study, we
      analyzed acute myeloid leukemic cells for the expression of p75/AIRM-1. p75/AIRM
      1 marked the M5 (11/12) and M4 (2/2) but not the M1, M2, and M3 subtypes
      according to the French-American-British classification. Cell samples from 12
      acute myeloid leukemias were cultured in the presence of granulocyte/macrophage
      colony-stimulating factor. Addition to these cultures of anti-CD33 antibody
      resulted in approximately 70% inhibition of cell proliferation as assessed by
      [(3)H]thymidine uptake or by the recovery of viable cells. Anti-p75/AIRM-1
      antibody exerted a strong inhibitory effect only in two cases characterized by a
      high in vitro proliferation rate. After crosslinking of CD33 (but not of p75/AIRM
      1), leukemic cells bound Annexin V and displayed changes in their light
      scattering properties and nucleosomal DNA fragmentation, thus providing evidence
      for the occurrence of apoptotic cell death. Remarkably, when anti-CD33 antibody
      was used in combination with concentrations of etoposide insufficient to induce
      apoptosis when used alone, a synergistic effect could be detected in the
      induction of leukemic cell death. These studies provide the rationale for new
      therapeutic approaches in myeloid leukemias by using both chemotherapy and
      apoptosis-inducing mAbs.

PMID- 11320213
TI  - S-nitrosothiol repletion by an inhaled gas regulates pulmonary function.
AB  - NO synthases are widely distributed in the lung and are extensively involved in
      the control of airway and vascular homeostasis. It is recognized, however, that
      the O(2)-rich environment of the lung may predispose NO toward toxicity. These
      Janus faces of NO are manifest in recent clinical trials with inhaled NO gas,
      which has shown therapeutic benefit in some patient populations but increased
      morbidity in others. In the airways and circulation of humans, most NO
      bioactivity is packaged in the form of S-nitrosothiols (SNOs), which are
      relatively resistant to toxic reactions with O(2)/O(2)(-). This finding has led
      to the proposition that channeling of NO into SNOs may provide a natural defense
      against lung toxicity. The means to selectively manipulate the SNO pool, however,
      has not been previously possible. Here we report on a gas, O-nitrosoethanol
      (ENO), which does not react with O(2) or release NO and which markedly increases
      the concentration of indigenous species of SNO within airway lining fluid.
      Inhalation of ENO provided immediate relief from hypoxic pulmonary
      vasoconstriction without affecting systemic hemodynamics. Further, in a porcine
      model of lung injury, there was no rebound in cardiopulmonary hemodynamics or
      fall in oxygenation on stopping the drug (as seen with NO gas), and additionally
      ENO protected against a decline in cardiac output. Our data suggest that SNOs
      within the lung serve in matching ventilation to perfusion, and can be
      manipulated for therapeutic gain. Thus, ENO may be of particular benefit to
      patients with pulmonary hypertension, hypoxemia, and/or right heart failure, and
      may offer a new therapeutic approach in disorders such as asthma and cystic
      fibrosis, where the airways may be depleted of SNOs.

PMID- 11320215
TI  - Does recombination improve selection on codon usage? Lessons from nematode and
      fly complete genomes.
AB  - Understanding the factors responsible for variations in mutation patterns and
      selection efficacy along chromosomes is a prerequisite for deciphering genome
      sequences. Population genetics models predict a positive correlation between the
      efficacy of selection at a given locus and the local rate of recombination
      because of Hill-Robertson effects. Codon usage is considered one of the most
      striking examples that support this prediction at the molecular level. In a wide
      range of species including Caenorhabditis elegans and Drosophila melanogaster,
      codon usage is essentially shaped by selection acting for translational
      efficiency. Codon usage bias correlates positively with recombination rate in
      Drosophila, apparently supporting the hypothesis that selection on codon usage is
      improved by recombination. Here we present an exhaustive analysis of codon usage
      in C. elegans and D. melanogaster complete genomes. We show that in both genomes
      there is a positive correlation between recombination rate and the frequency of
      optimal codons. However, we demonstrate that in both species, this effect is due
      to a mutational bias toward G and C bases in regions of high recombination rate,
      possibly as a direct consequence of the recombination process. The correlation
      between codon usage bias and recombination rate in these species appears to be
      essentially determined by recombination-dependent mutational patterns, rather
      than selective effects. This result highlights that it is necessary to take into
      account the mutagenic effect of recombination to understand the evolutionary role
      and impact of recombination.

PMID- 11320214
TI  - Host microarray analysis reveals a role for the Salmonella response regulator
      phoP in human macrophage cell death.
AB  - Bacterial pathogens manipulate host cells to promote pathogen survival and
      dissemination. We used a 22,571 human cDNA microarray to identify host pathways
      that are affected by the Salmonella enterica subspecies typhimurium phoP gene, a
      transcription factor required for virulence, by comparing the expression profiles
      of human monocytic tissue culture cells infected with either the wild-type
      bacteria or a phoPTn10 mutant strain. Both wild-type and phoPTn10 bacteria
      induced a common set of genes, many of which are proinflammatory. Differentially
      expressed genes included those that affect host cell death, suggesting that the
      phoP regulatory system controls bacterial genes that alter macrophage survival.
      Subsequent experiments showed that the phoPTn10 mutant strain is defective for
      killing both cultured and primary human macrophages but is able to replicate
      intracellularly. These experiments indicate that phoP plays a role in Salmonella
      induced human macrophage cell death.

PMID- 11320216
TI  - Nonlinear-dynamical arrhythmia control in humans.
AB  - Nonlinear-dynamical control techniques, also known as chaos control, have been
      used with great success to control a wide range of physical systems. Such
      techniques have been used to control the behavior of in vitro excitable
      biological tissue, suggesting their potential for clinical utility. However, the
      feasibility of using such techniques to control physiological processes has not
      been demonstrated in humans. Here we show that nonlinear-dynamical control can
      modulate human cardiac electrophysiological dynamics by rapidly stabilizing an
      unstable target rhythm. Specifically, in 52/54 control attempts in five patients,
      we successfully terminated pacing-induced period-2 atrioventricular-nodal
      conduction alternans by stabilizing the underlying unstable steady-state
      conduction. This proof-of-concept demonstration shows that nonlinear-dynamical
      control techniques are clinically feasible and provides a foundation for
      developing such techniques for more complex forms of clinical arrhythmia.

PMID- 11320217
TI  - FGF-2 regulation of neurogenesis in adult hippocampus after brain injury.
AB  - Fibroblast growth factor-2 (FGF-2) promotes proliferation of neuroprogenitor
      cells in culture and is up-regulated within brain after injury. Using mice
      genetically deficient in FGF-2 (FGF-2(-/-) mice), we addressed the importance of
      endogenously generated FGF-2 on neurogenesis within the hippocampus, a structure
      involved in spatial, declarative, and contextual memory, after seizures or
      ischemic injury. BrdUrd incorporation was used to mark dividing neuroprogenitor
      cells and NeuN expression to monitor their differentiation into neurons. In the
      wild-type strain, hippocampal FGF-2 increased after either kainic acid injection
      or middle cerebral artery occlusion, and the numbers of BrdUrd/NeuN-positive
      cells significantly increased on days 9 and 16 as compared with the controls. In
      FGF-2(-/-) mice, BrdUrd labeling was attenuated after kainic acid or middle
      cerebral artery occlusion, as was the number of neural cells colabeled with both
      BrdUrd and NeuN. After FGF-2(-/-) mice were injected intraventricularly with a
      herpes simplex virus-1 amplicon vector carrying FGF-2 gene, the number of BrdUrd
      labeled cells increased significantly to values equivalent to wild-type
      littermates after kainate seizures. These results indicate that endogenously
      synthesized FGF-2 is necessary and sufficient to stimulate proliferation and
      differentiation of neuroprogenitor cells in the adult hippocampus after brain
      insult.

PMID- 11320218
TI  - Radial and longitudinal diffusion of myoglobin in single living heart and
      skeletal muscle cells.
AB  - We have used a fluorescence recovery after photobleaching (FRAP) technique to
      measure radial diffusion of myoglobin and other proteins in single skeletal and
      cardiac muscle cells. We compare the radial diffusivities, D(r) (i.e., diffusion
      perpendicular to the long fiber axis), with longitudinal ones, D(l) (i.e.,
      parallel to the long fiber axis), both measured by the same technique, for
      myoglobin (17 kDa), lactalbumin (14 kDa), and ovalbumin (45 kDa). At 22 degrees
      C, D(l) for myoglobin is 1.2 x 10(-7) cm(2)/s in soleus fibers and 1.1 x 10(-7)
      cm(2)/s in cardiomyocytes. D(l) for lactalbumin is similar in both cell types.
      D(r) for myoglobin is 1.2 x 10(-7) cm(2)/s in soleus fibers and 1.1 x 10(-7)
      cm(2)/s in cardiomyocytes and, again, similar for lactalbumin. D(l) and D(r) for
      ovalbumin are 0.5 x 10(-7) cm(2)/s. In the case of myoglobin, both D(l) and D(r)
      at 37 degrees C are about 80% higher than at 22 degrees C. We conclude that
      intracellular diffusivity of myoglobin and other proteins (i) is very low in
      striated muscle cells, approximately 1/10 of the value in dilute protein
      solution, (ii) is not markedly different in longitudinal and radial direction,
      and (iii) is identical in heart and skeletal muscle. A Krogh cylinder model
      calculation holding for steady-state tissue oxygenation predicts that, based on
      these myoglobin diffusivities, myoglobin-facilitated oxygen diffusion contributes
      4% to the overall intracellular oxygen transport of maximally exercising skeletal
      muscle and less than 2% to that of heart under conditions of high work load.

PMID- 11320219
TI  - Protein quantification from complex protein mixtures using a proteomics
      methodology with single-cell resolution.
AB  - We have developed an extremely sensitive technique, termed immuno-detection
      amplified by T7 RNA polymerase (IDAT) that is capable of monitoring proteins,
      lipids, and metabolites and their modifications at the single-cell level. A
      double-stranded oligonucleotide containing the T7 promoter is conjugated to an
      antibody (Ab), and then T7 RNA polymerase is used to amplify RNA from the double
      stranded oligonucleotides coupled to the Ab in the Ab-antigen complex. By using
      this technique, we are able to detect the p185(her2/neu) receptor from the crude
      lysate of T6-17 cells at 10(-13) dilution, which is 10(9)-fold more sensitive
      than the conventional ELISA method. Single-chain Fv fragments or complementarity
      determining region peptides of the Ab also can be substituted for the Ab in IDAT.
      In a modified protocol, the oligonucleotide has been coupled to an Ab against a
      common epitope to create a universal detector species. With the linear
      amplification ability of T7 RNA polymerase, IDAT represents a significant
      improvement over immuno-PCR in terms of sensitivity and has the potential to
      provide a robotic platform for proteomics.

PMID- 11320220
TI  - Regulation of toxin synthesis in Clostridium difficile by an alternative RNA
      polymerase sigma factor.
AB  - Clostridium difficile, a causative agent of antibiotic-associated diarrhea and
      its potentially lethal form, pseudomembranous colitis, produces two large protein
      toxins that are responsible for the cellular damage associated with the disease.
      The level of toxin production appears to be critical for determining the severity
      of the disease, but the mechanism by which toxin synthesis is regulated is
      unknown. The product of a gene, txeR, that lies just upstream of the tox gene
      cluster was shown to be needed for tox gene expression in vivo and to activate
      promoter-specific transcription of the tox genes in vitro in conjunction with RNA
      polymerases from C. difficile, Bacillus subtilis, or Escherichia coli. TxeR was
      shown to function as an alternative sigma factor for RNA polymerase. Because
      homologs of TxeR regulate synthesis of toxins and a bacteriocin in other
      Clostridium species, TxeR appears to be a prototype for a novel mode of
      regulation of toxin genes.

PMID- 11320221
TI  - Y chromosome polymorphism is a strong determinant of male fitness in Drosophila
      melanogaster.
AB  - In many species, the Y (or W) chromosome carries relatively few functional genes.
      This observation motivates the null hypothesis that the Y will be a minor
      contributor to genetic variation for fitness. Previous data and theory supported
      the null hypothesis, but evidence presented here shows that the Y of Drosophila
      melanogaster is a major determinant of a male's total fitness, with standing
      genetic variation estimated to be 68% of that of an entire X/autosome genomic
      haplotype. Most Y-linked genes are expressed during spermatogenesis, and
      correspondingly, we found that the Y influences fitness primarily through its
      effect on a male's reproductive success (sperm competition and/or mating success)
      rather than his egg-to-adult viability. But the fitness of a Y highly depended on
      the genetic makeup of its bearer, reverting from high to low in different genetic
      backgrounds. This pattern leads to large epistatic (inconsistent among
      backgrounds) but no additive (consistent among backgrounds) Y-linked genetic
      variance for fitness. On a microevolutionary scale, the observed large epistatic
      variation on the Y substantially reduces heritable variation for fitness among
      males, and on a macroevolutionary scale, the Y produces strong selection for
      genomic rearrangements that move interacting genes onto the nonrecombining region
      of the Y.

PMID- 11320222
TI  - Non-Arrhenius kinetics for the loop closure of a DNA hairpin.
AB  - Intramolecular chain diffusion is an elementary process in the conformational
      fluctuations of the DNA hairpin-loop. We have studied the temperature and
      viscosity dependence of a model DNA hairpin-loop by FRET (fluorescence resonance
      energy transfer) fluctuation spectroscopy (FRETfs). Apparent thermodynamic
      parameters were obtained by analyzing the correlation amplitude through a two
      state model and are consistent with steady-state fluorescence measurements. The
      kinetics of closing the loop show non-Arrhenius behavior, in agreement with
      theoretical prediction and other experimental measurements on peptide folding.
      The fluctuation rates show a fractional power dependence (beta = 0.83) on the
      solution viscosity. A much slower intrachain diffusion coefficient in comparison
      to that of polypeptides was derived based on the first passage time theory of SSS
      [Szabo, A., Schulten, K. & Schulten, Z. (1980) J. Chem. Phys. 72, 4350-4357],
      suggesting that intrachain interactions, especially stacking interaction in the
      loop, might increase the roughness of the free energy surface of the DNA hairpin
      loop.

PMID- 11320223
TI  - Growth factors regulate phototransduction in retinal rods by modulating cyclic
      nucleotide-gated channels through dephosphorylation of a specific tyrosine
      residue.
AB  - Illumination of vertebrate rod photoreceptors leads to a decrease in the
      cytoplasmic cGMP concentration and closure of cyclic nucleotide-gated (CNG)
      channels. Except for Ca(2+), which plays a negative feedback role in adaptation,
      and 11-cis-retinal, supplied by the retinal pigment epithelium, all of the
      biochemical machinery of phototransduction is thought to be contained within rod
      outer segments without involvement of extrinsic regulatory molecules. Here we
      show that insulin-like growth factor-I (IGF-I), a paracrine factor released from
      the retinal pigment epithelium, alters phototransduction by rapidly increasing
      the cGMP sensitivity of CNG channels. The IGF-I-signaling pathway ultimately
      involves a protein tyrosine phosphatase that catalyzes dephosphorylation of a
      specific residue in the alpha-subunit of the rod CNG channel protein. IGF-I
      conjointly accelerates the kinetics and increases the amplitude of the light
      response, distinct from events that accompany adaptation. These effects of IGF-I
      could result from the enhancement of the cGMP sensitivity of CNG channels. Hence,
      in addition to long-term control of development and survival of rods, growth
      factors regulate phototransduction in the short term by modulating CNG channels.

PMID- 11320224
TI  - Rac and Cdc42 GTPases control hematopoietic stem cell shape, adhesion, migration,
      and mobilization.
AB  - Critical to homeostasis of blood cell production by hematopoietic stem/progenitor
      (HSC/P) cells is the regulation of HSC/P retention within the bone marrow
      microenvironment and migration between the bone marrow and the blood. Key
      extracellular regulatory elements for this process have been defined (cell-cell
      adhesion, growth factors, chemokines), but the mechanism by which HSC/P cells
      reconcile multiple external signals has not been elucidated. Rac and related
      small GTPases are candidates for this role and were studied in HSC/P deficient in
      Rac2, a hematopoietic cell-specific family member. Rac2 appears to be critical
      for HSC/P adhesion both in vitro and in vivo, whereas a compensatory increase in
      Cdc42 activation regulates HSC/P migration. This genetic analysis provides
      physiological evidence of cross-talk between GTPase proteins and suggests that a
      balance of these two GTPases controls HSC/P adhesion and mobilization in vivo.

PMID- 11320225
TI  - Excitation-contraction coupling is unaffected by drastic alteration of the
      sequence surrounding residues L720-L764 of the alpha 1S II-III loop.
AB  - The II-III loop of the skeletal muscle dihydropyridine receptor (DHPR) alpha(1S)
      subunit is responsible for bidirectional-signaling interactions with the
      ryanodine receptor (RyR1): transmitting an orthograde, excitation-contraction
      (EC) coupling signal to RyR1 and receiving a retrograde, current-enhancing signal
      from RyR1. Previously, several reports argued for the importance of two distinct
      regions of the skeletal II-III loop (residues R681-L690 and residues L720-Q765,
      respectively), claiming for each a key function in DHPR-RyR1 communication. To
      address whether residues 720-765 of the II-III loop are sufficient to enable
      skeletal-type (Ca(2+) entry-independent) EC coupling and retrograde interaction
      with RyR1, we constructed a green fluorescent protein (GFP)-tagged chimera (GFP
      SkLM) having rabbit skeletal (Sk) DHPR sequence except for a II-III loop (L) from
      the DHPR of the house fly, Musca domestica (M). The Musca II-III loop (75%
      dissimilarity to alpha(1S)) has no similarity to alpha(1S) in the regions R681
      L690 and L720-Q765. GFP-SkLM expressed in dysgenic myotubes (which lack
      endogenous alpha(1S) subunits) was unable to restore EC coupling and displayed
      strongly reduced Ca(2+) current densities despite normal surface expression
      levels and correct triad targeting (colocalization with RyR1). Introducing rabbit
      alpha(1S) residues L720-L764 into the Musca II-III loop of GFP-SkLM (substitution
      for Musca DHPR residues E724-T755) completely restored bidirectional coupling,
      indicating its dependence on alpha(1S) loop residues 720-764 but its independence
      from other regions of the loop. Thus, 45 alpha(1S)-residues embedded in a very
      dissimilar background are sufficient to restore bidirectional coupling,
      indicating that these residues may be a site of a protein-protein interaction
      required for bidirectional coupling.

PMID- 11320226
TI  - Acclimation of photosynthetic microorganisms to changing ambient CO2
      concentration.

PMID- 11320228
TI  - Sea urchin recovery from mass mortality: new hope for Caribbean coral reefs?

PMID- 11320227
TI  - How activated receptors couple to G proteins.

PMID- 11320229
TI  - mRNA display: diversity matters during in vitro selection.

PMID- 11320230
TI  - The future of electronics manufacturing is revealed in the fine print.

PMID- 11320231
TI  - From molecular genetics to archaeogenetics.

PMID- 11320232
TI  - Animals know more than we used to think.

PMID- 11320233
TI  - Paper-like electronic displays: large-area rubber-stamped plastic sheets of
      electronics and microencapsulated electrophoretic inks.
AB  - Electronic systems that use rugged lightweight plastics potentially offer
      attractive characteristics (low-cost processing, mechanical flexibility, large
      area coverage, etc.) that are not easily achieved with established silicon
      technologies. This paper summarizes work that demonstrates many of these
      characteristics in a realistic system: organic active matrix backplane circuits
      (256 transistors) for large ( approximately 5 x 5-inch) mechanically flexible
      sheets of electronic paper, an emerging type of display. The success of this
      effort relies on new or improved processing techniques and materials for plastic
      electronics, including methods for (i) rubber stamping (microcontact printing)
      high-resolution ( approximately 1 microm) circuits with low levels of defects and
      good registration over large areas, (ii) achieving low leakage with thin
      dielectrics deposited onto surfaces with relief, (iii) constructing high
      performance organic transistors with bottom contact geometries, (iv)
      encapsulating these transistors, (v) depositing, in a repeatable way, organic
      semiconductors with uniform electrical characteristics over large areas, and (vi)
      low-temperature ( approximately 100 degrees C) annealing to increase the on/off
      ratios of the transistors and to improve the uniformity of their characteristics.
      The sophistication and flexibility of the patterning procedures, high level of
      integration on plastic substrates, large area coverage, and good performance of
      the transistors are all important features of this work. We successfully
      integrate these circuits with microencapsulated electrophoretic "inks" to form
      sheets of electronic paper.

PMID- 11320234
TI  - Pitch perception: a dynamical-systems perspective.
AB  - Two and a half millennia ago Pythagoras initiated the scientific study of the
      pitch of sounds; yet our understanding of the mechanisms of pitch perception
      remains incomplete. Physical models of pitch perception try to explain from
      elementary principles why certain physical characteristics of the stimulus lead
      to particular pitch sensations. There are two broad categories of pitch
      perception models: place or spectral models consider that pitch is mainly related
      to the Fourier spectrum of the stimulus, whereas for periodicity or temporal
      models its characteristics in the time domain are more important. Current models
      from either class are usually computationally intensive, implementing a series of
      steps more or less supported by auditory physiology. However, the brain has to
      analyze and react in real time to an enormous amount of information from the ear
      and other senses. How is all this information efficiently represented and
      processed in the nervous system? A proposal of nonlinear and complex systems
      research is that dynamical attractors may form the basis of neural information
      processing. Because the auditory system is a complex and highly nonlinear
      dynamical system, it is natural to suppose that dynamical attractors may carry
      perceptual and functional meaning. Here we show that this idea, scarcely
      developed in current pitch models, can be successfully applied to pitch
      perception.

PMID- 11320235
TI  - The asymptotic distribution of canonical correlations and vectors in higher-order
      cointegrated models.
AB  - The study of the large-sample distribution of the canonical correlations and
      variates in cointegrated models is extended from the first-order autoregression
      model to autoregression of any (finite) order. The cointegrated process
      considered here is nonstationary in some dimensions and stationary in some other
      directions, but the first difference (the "error-correction form") is stationary.
      The asymptotic distribution of the canonical correlations between the first
      differences and the predictor variables as well as the corresponding canonical
      variables is obtained under the assumption that the process is Gaussian. The
      method of analysis is similar to that used for the first-order process.

PMID- 11320236
TI  - Structure and function in rhodopsin: Mass spectrometric identification of the
      abnormal intradiscal disulfide bond in misfolded retinitis pigmentosa mutants.
AB  - Retinitis pigmentosa (RP) point mutations in both the intradiscal (ID) and
      transmembrane domains of rhodopsin cause partial or complete misfolding of
      rhodopsin, resulting in loss of 11-cis-retinal binding. Previous work has shown
      that misfolding is caused by the formation of a disulfide bond in the ID domain
      different from the native Cys-110-Cys-187 disulfide bond in native rhodopsin.
      Here we report on direct identification of the abnormal disulfide bond in
      misfolded RP mutants in the transmembrane domain by mass spectrometric analysis.
      This disulfide bond is between Cys-185 and Cys-187, the same as previously
      identified in misfolded RP mutations in the ID domain. The strategy described
      here should be generally applicable to identification of disulfide bonds in other
      integral membrane proteins.

PMID- 11320238
TI  - Mapping of contact sites in complex formation between light-activated rhodopsin
      and transducin by covalent crosslinking: use of a chemically preactivated
      reagent.
AB  - Contact sites in interaction between light-activated rhodopsin and transducin (T)
      have been investigated by using a chemically preactivated crosslinking reagent, N
      succinimidyl 3-(2-pyridyldithio)propionate. The 3 propionyl-N-succinimidyl group
      in the reagent was attached by a disulfide exchange reaction to rhodopsin mutants
      containing single reactive cysteine groups in the cytoplasmic loops. Complex
      formation between the derivatized rhodopsin mutants and T was carried out by
      illumination at lambda > 495 nm. Subsequent increase in pH (from 6 to 7.5 or
      higher) of the complex resulted in crosslinking of rhodopsin to the T(alpha)
      subunit. Crosslinking to T(alpha) was demonstrated for the rhodopsin mutants
      K141C, S240C, and K248C, and the crosslinked sites in T(alpha) were identified
      for the rhodopsin mutant S240C. The peptides carrying the crosslinking moiety
      were isolated from the trypsin-digested peptide mixture, and their identification
      was carried out by matrix-assisted laser desorption ionization-time of flight
      mass spectrometry. The main site of crosslinking is within the peptide sequence,
      Leu-19-Arg-28 at the N-terminal region of T(alpha). The total results show that
      both the N and the C termini of T(alpha) are in close vicinity to the third
      cytoplasmic loop of rhodopsin in the complex between rhodopsin and T.

PMID- 11320237
TI  - Mapping of contact sites in complex formation between transducin and light
      activated rhodopsin by covalent crosslinking: use of a photoactivatable reagent.
AB  - Interaction of light-activated rhodopsin with transducin (T) is the first event
      in visual signal transduction. We use covalent crosslinking approaches to map the
      contact sites in interaction between the two proteins. Here we use a
      photoactivatable reagent, N-[(2-pyridyldithio)-ethyl], 4-azido salicylamide. The
      reagent is attached to the SH group of cytoplasmic monocysteine rhodopsin mutants
      by a disulfide-exchange reaction with the pyridylthio group, and the derivatized
      rhodopsin then is complexed with T by illumination at lambda >495 nm. Subsequent
      irradiation of the complex at lambda310 nm generates covalent crosslinks between
      the two proteins. Crosslinking was demonstrated between T and a number of single
      cysteine rhodopsin mutants. However, sites of crosslinks were investigated in
      detail only between T and the rhodopsin mutant S240C (cytoplasmic loop V-VI).
      Crosslinking occurred predominantly with T(alpha). For identification of the
      sites of crosslinks in T(alpha), the strategy used involved: (i) derivatization
      of all of the free cysteines in the crosslinked proteins with N-ethylmaleimide;
      (ii) reduction of the disulfide bond linking the two proteins and isolation of
      all of the T(alpha) species carrying the crosslinked moiety with a free SH group;
      (iii) adduct formation of the latter with the N-maleimide moiety of the reagent,
      maleimido-butyryl-biocytin, containing a biotinyl group; (iv) trypsin degradation
      of the resulting T(alpha) derivatives and isolation of T(alpha) peptides carrying
      maleimido-butyryl-biocytin by avidin-agarose chromatography; and (v)
      identification of the isolated peptides by matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry. We found that
      crosslinking occurred mainly to two C-terminal peptides in T(alpha) containing
      the amino acid sequences 310-313 and 342-345.

PMID- 11320239
TI  - Solution 19F nuclear Overhauser effects in structural studies of the cytoplasmic
      domain of mammalian rhodopsin.
AB  - 19F nuclear Overhauser effects (NOEs) between fluorine labels on the cytoplasmic
      domain of rhodopsin solubilized in detergent micelles are reported. Previously,
      high-resolution solution (19)F NMR spectra of fluorine-labeled rhodopsin in
      detergent micelles were described, demonstrating the applicability of this
      technique to studies of tertiary structure in the cytoplasmic domain. To
      quantitate tertiary contacts we have applied a transient one-dimensional
      difference NOE solution (19)F NMR experiment to this system, permitting
      assessment of proximities between fluorine labels specifically incorporated into
      different regions of the cytoplasmic face. Three dicysteine substitution mutants
      (Cys-140-Cys-316, Cys-65-Cys-316, and Cys-139-Cys-251) were labeled by attachment
      of the trifluoroethylthio group through a disulfide linkage. Each mutant
      rhodopsin was prepared (8-10 mg) in dodecylmaltoside and analyzed at 20 degrees C
      by solution (19)F NMR. Distinct chemical shifts were observed for all of the
      rhodopsin (19)F labels in the dark. An up-field shift of the Cys-316 resonance in
      the Cys-65-Cys-316 mutant suggests a close proximity between the two residues.
      When analyzed for (19)F-(19)F NOEs, a moderate negative enhancement was observed
      for the Cys-65-Cys-316 pair and a strong negative enhancement was observed for
      the Cys-139-Cys-251 pair, indicating proximity between these sites. No NOE
      enhancement was observed for the Cys-140-Cys-316 pair. These NOE effects
      demonstrate a solution (19)F NMR method for analysis of tertiary contacts in high
      molecular weight proteins, including membrane proteins.

PMID- 11320240
TI  - Dynamics of Fos-Jun-NFAT1 complexes.
AB  - Transcription initiation in eukaryotes is controlled by nucleoprotein complexes
      formed through cooperative interactions among multiple transcription regulatory
      proteins. These complexes may be assembled via stochastic collisions or defined
      pathways. We investigated the dynamics of Fos-Jun-NFAT1 complexes by using a
      multicolor fluorescence resonance energy transfer assay. Fos-Jun heterodimers can
      bind to AP-1 sites in two opposite orientations, only one of which is populated
      in mature Fos-Jun-NFAT1 complexes. We studied the reversal of Fos-Jun binding
      orientation in response to NFAT1 by measuring the efficiencies of energy transfer
      from donor fluorophores linked to opposite ends of an oligonucleotide to an
      acceptor fluorophore linked to one subunit of the heterodimer. The reorientation
      of Fos-Jun by NFAT1 was not inhibited by competitor oligonucleotides or
      heterodimers. The rate of Fos-Jun reorientation was faster than the rate of
      heterodimer dissociation at some binding sites. The facilitated reorientation of
      Fos-Jun heterodimers therefore can enhance the efficiency of Fos-Jun-NFAT1
      complex formation. We also examined the influence of the preferred orientation of
      Fos-Jun binding on the stability and transcriptional activity of Fos-Jun-NFAT1
      complexes. Complexes formed at sites where Fos-Jun favored the same binding
      orientation in the presence and absence of NFAT1 exhibited an 8-fold slower
      dissociation rate than complexes formed at sites where Fos-Jun favored the
      opposite binding orientation. Fos-Jun-NFAT1 complexes also exhibited greater
      transcription activation at promoter elements that favored the same orientation
      of Fos-Jun binding in the presence and absence of NFAT1. Thus, the orientation of
      heterodimer binding can influence both the dynamics and promoter selectivity of
      multiprotein transcription regulatory complexes.

PMID- 11320241
TI  - Crystallographic structures of the ligand-binding domains of the androgen
      receptor and its T877A mutant complexed with the natural agonist
      dihydrotestosterone.
AB  - The structures of the ligand-binding domains (LBD) of the wild-type androgen
      receptor (AR) and the T877A mutant corresponding to that in LNCaP cells, both
      bound to dihydrotestosterone, have been refined at 2.0 A resolution. In contrast
      to the homodimer seen in the retinoid-X receptor and estrogen receptor LBD
      structures, the AR LBD is monomeric, possibly because of the extended C terminus
      of AR, which lies in a groove at the dimerization interface. Binding of the
      natural ligand dihydrotestosterone by the mutant LBD involves interactions with
      the same residues as in the wild-type receptor, with the exception of the side
      chain of threonine 877, which is an alanine residue in the mutant. This
      structural difference in the binding pocket can explain the ability of the mutant
      AR found in LNCaP cells (T877A) to accommodate progesterone and other ligands
      that the wild-type receptor cannot.

PMID- 11320242
TI  - Unnatural base pairs for specific transcription.
AB  - An unnatural base pair of 2-amino-6-(N,N-dimethylamino)purine (designated as x)
      and pyridin-2-one (designated as y) has been developed for specific
      transcription. The ribonucleoside triphosphates of y and a modified y, 5
      methylpyridin-2-one, are selectively incorporated into RNA opposite x in the
      templates by T7 RNA polymerase. In addition, the sequences of the DNA templates
      containing x can be confirmed by a dideoxynucleotide chain-terminator method
      supplemented with the deoxynucleoside triphosphate of y. The bulky dimethylamino
      group of x in the templates effectively eliminates noncognate pairing with the
      natural bases. These results enable RNA biosynthesis for the specific
      incorporation of unnatural nucleotides at the desired positions.

PMID- 11320243
TI  - Dynamic properties of the Ras switch I region and its importance for binding to
      effectors.
AB  - We have investigated the dynamic properties of the switch I region of the GTP
      binding protein Ras by using mutants of Thr-35, an invariant residue necessary
      for the switch function. Here we show that these mutants, previously used as
      partial loss-of-function mutations in cell-based assays, have a reduced affinity
      to Ras effector proteins without Thr-35 being involved in any interaction. The
      structure of Ras(T35S)(.)GppNHp was determined by x-ray crystallography. Whereas
      the overall structure is very similar to wildtype, residues from switch I are
      completely invisible, indicating that the effector loop region is highly mobile.
      (31)P-NMR data had indicated an equilibrium between two rapidly interconverting
      conformations, one of which (state 2) corresponds to the structure found in the
      complex with the effectors. (31)P-NMR spectra of Ras mutants (T35S) and (T35A) in
      the GppNHp form show that the equilibrium is shifted such that they occur
      predominantly in the nonbinding conformation (state 1). On addition of Ras
      effectors, Ras(T35S) but not Ras(T35A) shift to positions corresponding to the
      binding conformation. The structural data were correlated with kinetic
      experiments that show two-step binding reaction of wild-type and (T35S)Ras with
      effectors requires the existence of a rate-limiting isomerization step, which is
      not observed with T35A. The results indicate that minor changes in the switch
      region, such as removing the side chain methyl group of Thr-35, drastically
      affect dynamic behavior and, in turn, interaction with effectors. The dynamics of
      the switch I region appear to be responsible for the conservation of this
      threonine residue in GTP-binding proteins.

PMID- 11320244
TI  - Conversion of a maltose receptor into a zinc biosensor by computational design.
AB  - We have demonstrated that it is possible to radically change the specificity of
      maltose binding protein by converting it into a zinc sensor using a rational
      design approach. In this new molecular sensor, zinc binding is transduced into a
      readily detected fluorescence signal by use of an engineered conformational
      coupling mechanism linking ligand binding to reporter group response. An
      iterative progressive design strategy led to the construction of variants with
      increased zinc affinity by combining binding sites, optimizing the primary
      coordination sphere, and exploiting conformational equilibria. Intermediates in
      the design series show that the adaptive process involves both introduction and
      optimization of new functions and removal of adverse vestigial interactions. The
      latter demonstrates the importance of the rational design approach in uncovering
      cryptic phenomena in protein function, which cannot be revealed by the study of
      naturally evolved systems.

PMID- 11320245
TI  - Controlling small guanine-nucleotide-exchange factor function through cytoplasmic
      RNA intramers.
AB  - ADP-ribosylation factor (ARF) GTPases and their regulatory proteins have been
      implicated in the control of diverse biological functions. Two main classes of
      positive regulatory elements for ARF have been discovered so far: the large
      Sec7/Gea and the small cytohesin/ARNO families, respectively. These proteins
      harbor guanine-nucleotide-exchange factor (GEF) activity exerted by the common
      Sec7 domain. The availability of a specific inhibitor, the fungal metabolite
      brefeldin A, has enabled documentation of the involvement of the large GEFs in
      vesicle transport. However, because of the lack of such tools, the biological
      roles of the small GEFs have remained controversial. Here, we have selected a
      series of RNA aptamers that specifically recognize the Sec7 domain of cytohesin
      1. Some aptamers inhibit guanine-nucleotide exchange on ARF1, thereby preventing
      ARF activation in vitro. Among them, aptamer M69 exhibited unexpected specificity
      for the small GEFs, because it does not interact with or inhibit the GEF activity
      of the related Gea2-Sec7 domain, a member of the class of large GEFs. The
      inhibitory effect demonstrated in vitro clearly is observed as well in vivo,
      based on the finding that M69 produces similar results as a dominant-negative,
      GEF-deficient mutant of cytohesin 1: when expressed in the cytoplasm of T-cells,
      M69 reduces stimulated adhesion to intercellular adhesion molecule-1 and results
      in a dramatic reorganization of F-actin distribution. These highly specific
      cellular effects suggest that the ARF-GEF activity of cytohesin 1 plays an
      important role in cytoskeletal remodeling events of lymphoid cells.

PMID- 11320246
TI  - The preferred stoichiometry of c subunits in the rotary motor sector of
      Escherichia coli ATP synthase is 10.
AB  - The stoichiometry of c subunits in the H(+)-transporting F(o) rotary motor of ATP
      synthase is uncertain, the most recent suggestions varying from 10 to 14. The
      stoichiometry will determine the number of H(+) transported per ATP synthesized
      and will directly relate to the P/O ratio of oxidative phosphorylation. The
      experiments described here show that the number of c subunits in functional
      complexes of F(o)F(1) ATP synthase from Escherichia coli can be manipulated, but
      that the preferred number is 10. Mixtures of genetically fused cysteine
      substituted trimers (c(3)) and tetramers (c(4)) of subunit c were coexpressed and
      the c subunits crosslinked in the plasma membrane. Prominent products
      corresponding to oligomers of c(7) and c(10) were observed in the membrane and
      purified F(o)F(1) complex, indicating that the c(10) oligomer formed naturally.
      Oligomers larger than c(10) were also observed in the membrane fraction of cells
      expressing c(3) or c(4) individually, or in cells coexpressing c(3) and c(4)
      together, but these larger oligomers did not copurify with the functional
      F(o)F(1) complex and were concluded to be aberrant products of assembly in the
      membrane.

PMID- 11320247
TI  - Efficient pyrophosphorolysis by a hepatitis B virus polymerase may be a primer
      unblocking mechanism.
AB  - Effective antiviral agents are thought to inhibit hepatitis B virus (HBV) DNA
      synthesis irreversibly by chain termination because reverse transcriptases (RT)
      lack an exonucleolytic activity that can remove incorporated nucleotides.
      However, since the parameters governing this inhibition are poorly defined, fully
      delineating the catalytic mechanism of the HBV-RT promises to facilitate the
      development of antiviral drugs for treating chronic HBV infection. To this end,
      pyrophosphorolysis and pyrophosphate exchange, two nonhydrolytic RT activities
      that result in the removal of newly incorporated nucleotides, were characterized
      by using endogenous avian HBV replication complexes assembled in vivo. Although
      these activities are presumed to be physiologically irrelevant for every
      polymerase examined, the efficiency with which they are catalyzed by the avian
      HBV-RT strongly suggests that it is the first known polymerase to catalyze these
      reactions under replicative conditions. The ability to remove newly incorporated
      nucleotides during replication has important biological and clinical
      implications: these activities may serve a primer-unblocking function in vivo.
      Analysis of pyrophosphorolysis on chain-terminated DNA revealed that the potent
      anti-HBV drug beta-l-(-)-2',3'-dideoxy-3'-thiacytidine (3TC) was difficult to
      remove by pyrophosphorolysis, in contrast to ineffective chain terminators such
      as ddC. This disparity may account for the strong antiviral efficacy of 3TC
      versus that of ddC. The HBV-RT pyrophosphorolytic activity may therefore be a
      novel determinant of antiviral drug efficacy, and could serve as a target for
      future antiviral drug therapy. The strong inhibitory effect of cytoplasmic
      pyrophosphate concentrations on viral DNA synthesis may also partly account for
      the apparent slow rate of HBV genome replication.

PMID- 11320248
TI  - The Caenorhabditis elegans maternal-effect sterile proteins, MES-2, MES-3, and
      MES-6, are associated in a complex in embryos.
AB  - The Caenorhabditis elegans maternal-effect sterile genes, mes-2, mes-3, mes-4,
      and mes-6, encode nuclear proteins that are essential for germ-line development.
      They are thought to be involved in a common process because their mutant
      phenotypes are similar. MES-2 and MES-6 are homologs of Enhancer of zeste and
      extra sex combs, both members of the Polycomb group of chromatin regulators in
      insects and vertebrates. MES-3 is a novel protein, and MES-4 is a SET-domain
      protein. To investigate whether the MES proteins interact and likely function as
      a complex, we performed biochemical analyses on C. elegans embryo extracts.
      Results of immunoprecipitation experiments indicate that MES-2, MES-3, and MES-6
      are associated in a complex and that MES-4 is not associated with this complex.
      Based on in vitro binding assays, MES-2 and MES-6 interact directly, via the
      amino terminal portion of MES-2. Sucrose density gradient fractionation and gel
      filtration chromatography were performed to determine the Stokes radius and
      sedimentation coefficient of the MES-2/MES-3/MES-6 complex. Based on those two
      values, we estimate that the molecular mass of the complex is approximately 255
      kDa, close to the sum of the three known components. Our results suggest that the
      two C. elegans Polycomb group homologs (MES-2 and MES-6) associate with a novel
      partner (MES-3) to regulate germ-line development in C. elegans.

PMID- 11320249
TI  - Mutation in bone morphogenetic protein receptor-IB is associated with increased
      ovulation rate in Booroola Merino ewes.
AB  - Ewes from the Booroola strain of Australian Merino sheep are characterized by
      high ovulation rate and litter size. This phenotype is due to the action of the
      FecB(B) allele of a major gene named FecB, as determined by statistical analysis
      of phenotypic data. By genetic analysis of 31 informative half-sib families from
      heterozygous sires, we showed that the FecB locus is situated in the region of
      ovine chromosome 6 corresponding to the human chromosome 4q22-23 that contains
      the bone morphogenetic protein receptor IB (BMPR-IB) gene encoding a member of
      the transforming growth factor-beta (TGF-beta) receptor family. A nonconservative
      substitution (Q249R) in the BMPR-IB coding sequence was found to be associated
      fully with the hyperprolificacy phenotype of Booroola ewes. In vitro, ovarian
      granulosa cells from FecB(B)/FecB(B) ewes were less responsive than granulosa
      cells from FecB(+)/FecB(+) ewes to the inhibitory effect on steroidogenesis of
      GDF-5 and BMP-4, natural ligands of BMPR-IB. It is suggested that in
      FecB(B)/FecB(B) ewes, BMPR-IB would be inactivated partially, leading to an
      advanced differentiation of granulosa cells and an advanced maturation of
      ovulatory follicles.

PMID- 11320250
TI  - Cancer-predisposing mutations within the RING domain of BRCA1: loss of ubiquitin
      protein ligase activity and protection from radiation hypersensitivity.
AB  - BRCA1 is a breast and ovarian cancer-specific tumor suppressor that seems to be
      involved in transcription and DNA repair. Here we report that BRCA1 exhibits a
      bona fide ubiquitin (Ub) protein ligase (E3) activity, and that cancer
      predisposing mutations within the BRCA1 RING domain abolish its Ub ligase
      activity. Furthermore, these mutants are unable to reverse gamma-radiation
      hypersensitivity of BRCA1-null human breast cancer cells, HCC1937. Additionally,
      these mutations within the BRCA1 RING domain are not capable of restoring a G(2)
      + M checkpoint in HCC1937 cells. These results establish a link between Ub
      protein ligase activity and gamma-radiation protection function of BRCA1, and
      provide an explanation for why mutations within the BRCA1 RING domain predispose
      to cancer. Furthermore, we propose that the analysis of the Ub ligase activity of
      RING-domain mutations identified in patients may constitute an assay to predict
      predisposition to cancer.

PMID- 11320251
TI  - IL-4 determines eicosanoid formation in dendritic cells by down-regulation of 5
      lipoxygenase and up-regulation of 15-lipoxygenase 1 expression.
AB  - Dendritic cell (DC) differentiation from human CD34(+) hematopoietic progenitor
      cells (HPCs) can be triggered in vitro by a combination of cytokines consisting
      of stem cell factor, granulocyte-macrophage colony-stimulating factor, and tumor
      necrosis factor alpha. The immune response regulatory cytokines, IL-4 and IL-13,
      promote DC maturation from HPCs, induce monocyte-DC transdifferentiation, and
      selectively up-regulate 15-lipoxygenase 1 (15-LO-1) in blood monocytes. To gain
      more insight into cytokine-regulated eicosanoid production in DCs we studied the
      effects of IL-4/IL-13 on LO expression during DC differentiation. In the absence
      of IL-4, DCs that had been generated from CD34(+) HPCs in response to stem cell
      factor/granulocyte-macrophage colonystimulating factor/tumor necrosis factor
      alpha expressed high levels of 5-LO and 5-LO activating protein. However, a small
      subpopulation of eosinophil peroxidase(+) (EOS-PX) cells significantly expressed
      15-LO-1. Addition of IL-4 to differentiating DCs led to a marked and selective
      down-regulation of 5-LO but not of 5-LO activating protein in DCs and in EOS
      PX(+) cells and, when added at the onset of DC differentiation, also prevented 5
      LO up-regulation. Similar effects were observed during IL-4- or IL-13-dependent
      monocyte-DC transdifferentiation. Down-regulation of 5-LO was accompanied by up
      regulation of 15-LO-1, yielding 15-LO-1(+) 5-LO-deficient DCs. However,
      transforming growth factor beta1 counteracted the IL-4-dependent inhibition of 5
      LO but only minimally affected 15-LO-1 up-regulation. Thus, transforming growth
      factor beta1 plus IL-4 yielded large mature DCs that coexpress both LOs.
      Localization of 5-LO in the nucleus and of 15-LO-1 in the cytosol was maintained
      at all cytokine combinations in all DC phenotypes and in EOS-PX(+) cells. In the
      absence of IL-4, major eicosanoids of CD34(+)-derived DCs were 5S
      hydroxyeicosatetraenoic acid (5S-HETE) and leukotriene B(4), whereas the major
      eicosanoids of IL-4-treated DCs were 15S-HETE and 5S-15S-diHETE. These actions of
      IL-4/IL-13 reveal a paradigm of eicosanoid formation consisting of the inhibition
      of one and the stimulation of another LO in a single leukocyte lineage.

PMID- 11320252
TI  - Global survey of genetic variation in CCR5, RANTES, and MIP-1alpha: impact on the
      epidemiology of the HIV-1 pandemic.
AB  - Expression of CC chemokine receptor 5 (CCR5), the major coreceptor for HIV-1 cell
      entry, and its ligands (e.g., RANTES and MIP-1alpha) is widely regarded as
      central to the pathogenesis of HIV-1 infection. By surveying nearly 3,000 HIV+
      and HIV- individuals from worldwide populations for polymorphisms in the genes
      encoding RANTES, MIP-1alpha, and CCR5, we show that the evolutionary histories of
      human populations have had a significant impact on the distribution of variation
      in these genes, and that this may be responsible, in part, for the heterogeneous
      nature of the epidemiology of the HIV-1 pandemic. The varied distribution of
      RANTES haplotypes (AC, GC, and AG) associated with population-specific HIV-1
      transmission- and disease-modifying effects is a striking example. Homozygosity
      for the AC haplotype was associated with an increased risk of acquiring HIV-1 as
      well as accelerated disease progression in European Americans, but not in African
      Americans. Yet, the prevalence of the ancestral AC haplotype is high in
      individuals of African origin, but substantially lower in non-Africans. In a
      Japanese cohort, AG-containing RANTES haplotype pairs were associated with a
      delay in disease progression; however, we now show that their contribution to HIV
      1 pathogenesis and epidemiology in other parts of the world is negligible because
      the AG haplotype is infrequent in non-Far East Asians. Thus, the varied
      distribution of RANTES, MIP-1alpha, and CCR5 haplotype pairs and their population
      specific phenotypic effects on HIV-1 susceptibility and disease progression
      results in a complex pattern of biological determinants of HIV-1 epidemiology.
      These findings have important implications for the design, assessment, and
      implementation of effective HIV-1 intervention and prevention strategies.

PMID- 11320255
TI  - A wholly empirical explanation of perceived motion.
AB  - Because the retinal activity generated by a moving object cannot specify which of
      an infinite number of possible physical displacements underlies the stimulus, its
      real-world cause is necessarily uncertain. How, then, do observers respond
      successfully to sequences of images whose provenance is ambiguous? Here we
      explore the hypothesis that the visual system solves this problem by a
      probabilistic strategy in which perceived motion is generated entirely according
      to the relative frequency of occurrence of the physical sources of the stimulus.
      The merits of this concept were tested by comparing the directions and speeds of
      moving lines reported by subjects to the values determined by the probability
      distribution of all the possible physical displacements underlying the stimulus.
      The velocities reported by observers in a variety of stimulus contexts can be
      accounted for in this way.

PMID- 11320254
TI  - RNA is a structural element in retrovirus particles.
AB  - A single retroviral protein, Gag, is sufficient for virus particle assembly.
      While Gag is capable of specifically packaging the genomic RNA into the particle,
      this RNA species is unnecessary for particle assembly in vivo. In vitro, nucleic
      acids profoundly enhance the efficiency of assembly by recombinant Gag proteins,
      apparently by acting as "scaffolding" in the particle. To address the
      participation of RNA in retrovirus assembly in vivo, we analyzed murine leukemia
      virus particles that lack genomic RNA because of a deletion in the packaging
      signal of the viral RNA. We found that these particles contain cellular mRNA in
      place of genomic RNA. This result was particularly evident when Gag was expressed
      by using a Semliki Forest virus-derived vector: under these conditions, the
      Semliki Forest virus vector-directed mRNA became very abundant in the cells and
      was readily identified in the retroviral virus-like particles. Furthermore, we
      found that the retroviral cores were disrupted by treatment with RNase. Taken
      together, the data strongly suggest that RNA is a structural element in
      retrovirus particles.

PMID- 11320253
TI  - Alterations in the regulation of androgen-sensitive Cyp 4a monooxygenases cause
      hypertension.
AB  - Hypertension is a leading cause of cardiovascular, cerebral, and renal disease
      morbidity and mortality. Here we show that disruption of the Cyp 4a14 gene causes
      hypertension, which is, like most human hypertension, more severe in males. Male
      Cyp 4a14 (-/-) mice show increases in plasma androgens, kidney Cyp 4a12
      expression, and the formation of prohypertensive 20-hydroxyarachidonate.
      Castration normalizes the blood pressure of Cyp 4a14 (-/-) mice and minimizes Cyp
      4a12 expression and arachidonate omega-hydroxylation. Androgen replacement
      restores hypertensive phenotype, Cyp 4a12 expression, and 20-hydroxy-arachidonate
      formation. We conclude that the androgen-mediated regulation of Cyp 4a
      arachidonate monooxygenases is an important component of the renal mechanisms
      that control systemic blood pressures. These results provide direct evidence for
      a role of Cyp 4a isoforms in cardiovascular physiology, establish Cyp 4a14 (-/-)
      mice as a monogenic model for the study of cause/effect relationships between
      blood pressure, sex hormones, and P450 omega-hydroxylases, and suggest the human
      CYP 4A homologues as candidate genes for the analysis of the genetic and
      molecular basis of human hypertension.

PMID- 11320256
TI  - Dopamine D2 and D3 receptors are linked to the actin cytoskeleton via interaction
      with filamin A.
AB  - We have used a yeast two-hybrid approach to uncover protein interactions
      involving the D2-like subfamily of dopamine receptors. Using the third
      intracellular loop of the D2S and D3 dopamine receptors as bait to screen a human
      brain cDNA library, we identified filamin A (FLN-A) as a protein that interacts
      with both the D2 and D3 subtypes. The interaction with FLN-A was specific for the
      D2 and D3 receptors and was independently confirmed in pull-down and
      coimmunoprecipitation experiments. Deletion mapping localized the dopamine
      receptor-FLN-A interaction to the N-terminal segment of the D2 and D3 dopamine
      receptors and to repeat 19 of FLN-A. In cultures of dissociated rat striatum, FLN
      A and D2 receptors colocalized throughout neuronal somata and processes as well
      as in astrocytes. Expression of D2 dopamine receptors in FLN-A-deficient M2
      melanoma cells resulted in predominant intracellular localization of the D2
      receptors, whereas in FLN-A-reconstituted cells, the D2 receptor was
      predominantly localized at the plasma membrane. These results suggest that FLN-A
      may be required for proper cell surface expression of the D2 dopamine receptors.
      Association of D2 and D3 dopamine receptors with FLN-A provides a mechanism
      whereby specific dopamine receptor subtypes may be functionally linked to
      downstream signaling components via the actin cytoskeleton.

PMID- 11320257
TI  - Amygdala-enriched genes identified by microarray technology are restricted to
      specific amygdaloid subnuclei.
AB  - Microarray technology represents a potentially powerful method for identifying
      cell type- and regionally restricted genes expressed in the brain. Here we have
      combined a microarray analysis of differential gene expression among five
      selected brain regions, including the amygdala, cerebellum, hippocampus,
      olfactory bulb, and periaqueductal gray, with in situ hybridization. On average,
      0.3% of the 34,000 genes interrogated were highly enriched in each of the five
      regions, relative to the others. In situ hybridization performed on a subset of
      amygdala-enriched genes confirmed in most cases the overall region-specificity
      predicted by the microarray data and identified additional sites of brain
      expression not examined on the microarrays. Strikingly, the majority of these
      genes exhibited boundaries of expression within the amygdala corresponding to
      cytoarchitectonically defined subnuclei. These results define a unique set of
      molecular markers for amygdaloid subnuclei and provide tools to genetically
      dissect their functional roles in different emotional behaviors.

PMID- 11320258
TI  - Molecular mechanisms of cocaine reward: combined dopamine and serotonin
      transporter knockouts eliminate cocaine place preference.
AB  - Cocaine blocks uptake by neuronal plasma membrane transporters for dopamine
      (DAT), serotonin (SERT), and norepinephrine (NET). Cocaine reward/reinforcement
      has been linked to actions at DAT or to blockade of SERT. However, knockouts of
      neither DAT, SERT, or NET reduce cocaine reward/reinforcement, leaving
      substantial uncertainty about cocaine's molecular mechanisms for reward.
      Conceivably, the molecular bases of cocaine reward might display sufficient
      redundancy that either DAT or SERT might be able to mediate cocaine reward in the
      other's absence. To test this hypothesis, we examined double knockout mice with
      deletions of one or both copies of both the DAT and SERT genes. These mice
      display viability, weight gain, histologic features, neurochemical parameters,
      and baseline behavioral features that allow tests of cocaine influences. Mice
      with even a single wild-type DAT gene copy and no SERT copies retain cocaine
      reward/reinforcement, as measured by conditioned place-preference testing.
      However, mice with no DAT and either no or one SERT gene copy display no
      preference for places where they have previously received cocaine. The serotonin
      dependence of cocaine reward in DAT knockout mice is thus confirmed by the
      elimination of cocaine place preference in DAT/SERT double knockout mice. These
      results provide insights into the brain molecular targets necessary for cocaine
      reward in knockout mice that develop in their absence and suggest novel
      strategies for anticocaine medication development.

PMID- 11320259
TI  - Direct toxicity of nonsteroidal antiinflammatory drugs for renal medullary cells.
AB  - Antipyretic analgesics, taken in large doses over a prolonged period, cause a
      specific form of kidney disease, characterized by papillary necrosis and
      interstitial scarring. Epidemiological evidence incriminated mixtures of drugs
      including aspirin (ASA), phenacetin, and caffeine. The mechanism of toxicity is
      unclear. We tested the effects of ASA, acetaminophen (APAF, the active metabolite
      of phenacetin), caffeine, and other related drugs individually and in combination
      on mouse inner medullary collecting duct cells (mIMCD3). The number of rapidly
      proliferating cells was reduced by approximately 50% by 0.5 mM ASA, salicylic
      acid, or APAF. The drugs had less effect on confluent cells, which proliferate
      slowly. Thus, the slow in vivo turnover of IMCD cells could explain why clinical
      toxicity requires very high doses of these drugs over a very long period.
      Caffeine greatly potentiated the effect of acetaminophen, pointing to a potential
      danger of the mixture. Cyclooxygenase (COX) inhibitors, indomethacin and NS-398,
      did not reduce cell number except at concentrations greatly in excess of those
      that inhibit COX. Therefore, COX inhibition alone is not toxic. APAF arrests most
      cells in late G(1) and S and produces a mixed form of cell death with both
      oncosis (swollen cells and nuclei) and apoptosis. APAF is known to inhibit the
      synthesis of DNA and cause chromosomal aberrations due to inhibition of
      ribonucleotide reductase. Such effects of APAF might account for renal medullary
      cell death in vivo and development of uroepithelial tumors from surviving cells
      that have chromosomal aberrations.

PMID- 11320260
TI  - Distinct gene-specific mechanisms of arrhythmia revealed by cardiac gene transfer
      of two long QT disease genes, HERG and KCNE1.
AB  - The long QT syndrome (LQTS) is a heritable disorder that predisposes to sudden
      cardiac death. LQTS is caused by mutations in ion channel genes including HERG
      and KCNE1, but the precise mechanisms remain unclear. To clarify this situation
      we injected adenoviral vectors expressing wild-type or LQT mutants of HERG and
      KCNE1 into guinea pig myocardium. End points at 48-72 h included
      electrophysiology in isolated myocytes and electrocardiography in vivo. HERG
      increased the rapid component, I(Kr), of the delayed rectifier current, thereby
      accelerating repolarization, increasing refractoriness, and diminishing beat-to
      beat action potential variability. Conversely, HERG-G628S suppressed I(Kr)
      without significantly delaying repolarization. Nevertheless, HERG-G628S
      abbreviated refractoriness and increased beat-to-beat variability, leading to
      early afterdepolarizations (EADs). KCNE1 increased the slow component of the
      delayed rectifier, I(Ks), without clear phenotypic sequelae. In contrast, KCNE1
      D76N suppressed I(Ks) and markedly slowed repolarization, leading to frequent
      EADs and electrocardiographic QT prolongation. Thus, the two genes predispose to
      sudden death by distinct mechanisms: the KCNE1 mutant flagrantly undermines
      cardiac repolarization, and HERG-G628S subtly facilitates the genesis and
      propagation of premature beats. Our ability to produce electrocardiographic long
      QT in vivo with a clinical KCNE1 mutation demonstrates the utility of somatic
      gene transfer in creating genotype-specific disease models.

PMID- 11320270
TI  - Colorectal cancer: does early detection matter?

PMID- 11320271
TI  - The menopause and its treatment in perspective.

PMID- 11320272
TI  - Hypophosphataemia in anorexia nervosa.

PMID- 11320273
TI  - Hutchinson-Guilford progeria syndrome.

PMID- 11320274
TI  - Ethical, professional, and legal obligations in clinical practice: a series of
      discussion topics for postgraduate medical education. Topic 2: consent and legal
      competence.

PMID- 11320275
TI  - Management of the impalpable testis: a six year review together with a national
      experience.
AB  - The management of undescended testes remains variable, and the use of laparoscopy
      for localisation is controversial. This study reviews the need for laparoscopy
      and also assesses the current practice among a cohort of surgeons.A retrospective
      review of all patients undergoing orchidopexy was performed, together with a
      postal survey of all members of the Welsh Surgical Society. Of the 139
      orchidopexies performed, the testis was deemed impalpable in 39 (28%) cases. All
      patients were treated with groin exploration, and only in two (5%) patients was
      the testis not located. From the survey, replies were received from 90 (81%)
      surgeons, of whom 65 (72%) were still performing orchidopexy. Forty eight (74%)
      surgeons performed orchidopexy between the age of 2 and 3, and only 32 (36%)
      performed preoperative investigations. The follow up period was variable with the
      majority of patients seen at six weeks. Laparoscopy for the impalpable testis is
      not initially warranted. An inguinal exploration is regarded as the definitive
      investigation. This has the advantage of providing the diagnosis and treatment in
      the majority of cases.

PMID- 11320276
TI  - Importance of family history in type 2 black South African diabetic patients.
AB  - OBJECTIVE: To assess the family history of diabetes in type 2 black South African
      diabetics with emphasis on the parental phenotype. DESIGN: Prospective case
      control study in which family histories were obtained from patients. SETTING:
      Diabetic clinic of a provincial teaching hospital in the Transkei region of South
      Africa. SUBJECTS: A total of 1111 type 2 diabetics attending the diabetic clinic
      and 687 controls. MAIN OUTCOME MEASURES: History of diabetes in parents,
      siblings, maternal and paternal grandparents, aunts, and uncles. RESULTS:
      Altogether 27.3% of diabetic subjects had a family history of diabetes compared
      with 8.4% in the control group (p<0.01). Among the group with positive family
      history 82.6% reported only one diabetic family member, while 17.4% reported at
      least two relatives; 6.6% had a diabetic relative from both maternal and paternal
      sides, and 87.8% had first degree relative with diabetes. Among them there was a
      significant maternal aggregation with 64.7% of patients having a diabetic mother
      compared with 27% who had a diabetic father (p<0.01). No maternal effect was
      observed among the second and third degree relatives. Patients with positive
      family history had an earlier onset of diabetes than those without family history
      (p<0.01). CONCLUSION: These data suggest that type 2 diabetes is heritable in
      black South African diabetics. It is also likely that maternal influences may
      play an important part.

PMID- 11320277
TI  - Human immunoglobulin for diabetic amyotrophy--a promising prospect?
AB  - Diabetic neuropathies are universally recognised and cause significant morbidity.
      At present improving glycaemic control is the only recognised treatment. A man
      with type 2 diabetes presented with disabling asymmetric lower limb proximal
      neuropathy. Rapid clinical, functional, and electrical improvement followed
      treatment with intravenous immunoglobulin. The aetiology of diabetic amyotrophy
      remains controversial but there is evidence for an immune mediated process and
      this case suggests a role for immunoglobulin in the management of this
      debilitating condition.

PMID- 11320278
TI  - Acute diquat poisoning with intracerebral bleeding.
AB  - A case of severe diquat poisoning complicated by the development of aggressive
      behaviour, oliguric renal failure, and intracerebral bleeding is described. The
      patient was successfully managed and made a complete recovery. In this paper
      special attention has been given to the major clinical differences between diquat
      and paraquat intoxication.

PMID- 11320279
TI  - Nephrotic syndrome and mesenteric infarction secondary to metastatic
      mesothelioma.
AB  - Malignant mesothelioma can present insidiously with progressive breathlessness
      and chest pain. Paraneoplastic, or non-chest related, presentations are very
      rare. The case of an elderly man with occupational exposure to asbestos who
      presented with nephrotic syndrome due to minimal change nephropathy in the
      context of advanced pleural mesothelial malignancy is reported.

PMID- 11320280
TI  - Autoamputation of the tongue.
AB  - Autoamputation is an uncommon phenomenon that has been reported for the fingers,
      toes, appendix, ovary, spleen, etc. Autoamputation of the tongue has never been
      reported. An elderly man with carcinoma of lateral pharyngeal wall and tonsil
      presented with an autoamputated tongue that was attached to the oral cavity with
      a thin band. The patient required detachment of the tongue and tracheostomy
      followed by radiotherapy for the primary tumour.

PMID- 11320281
TI  - Aspergillus thyroiditis.

PMID- 11320282
TI  - Future clinical role of nurses in the United Kingdom.

PMID- 11320283
TI  - An elderly woman with dyspnoea and bronchorrhoea. Bronchioloalveolar carcinoma.

PMID- 11320284
TI  - Unexplained weight loss and a palpable abdominal mass in a middle aged woman.
      Abdominal tuberculosis.

PMID- 11320285
TI  - Low back pain in a child--a diagnostic dilemma. Acute lymphoblastic leukaemia
      causing osteopenia.

PMID- 11320286
TI  - Atopy, proptosis, and nasal polyposis. Allergic fungal sinusitis with proptosis.

PMID- 11320287
TI  - Recurrent syncope. Drug induced long QT syndrome.

PMID- 11320289
TI  - An 80 year old woman with intermittent severe vomiting. Giant intrathoracic
      hiatus hernia.

PMID- 11320290
TI  - Pleuropericardial effusion in a 50 year old woman. Pleuropericardial effusion
      caused by adult inset Still's disease.

PMID- 11320295
TI  - Sequential occurrence within three years in a premenopausal woman of cervical,
      ovarian, and endometrial cancers.

PMID- 11320302
TI  - Structures of three diphtheria toxin repressor (DtxR) variants with decreased
      repressor activity.
AB  - The diphtheria toxin repressor (DtxR) from Corynebacterium diphtheriae regulates
      the expression of the gene on corynebacteriophages that encodes diphtheria toxin
      (DT). Other genes regulated by DtxR include those that encode proteins involved
      in siderophore-mediated iron uptake. DtxR requires activation by divalent metals
      and holo-DtxR is a dimeric regulator with two distinct metal-binding sites per
      three-domain monomer. At site 1, three side chains and a sulfate or phosphate
      anion are involved in metal coordination. In the DtxR-DNA complex this anion is
      replaced by the side chain of Glu170 provided by the third domain of the
      repressor. At site 2 the metal ion is coordinated exclusively by constituents of
      the polypeptide chain. In this paper, five crystal structures of three DtxR
      variants focusing on residues Glu20, Arg80 and Cys102 are reported. The
      resolution of these structures ranges from 2.3 to 2.8 A. The side chain of Glu20
      provided by the DNA-binding domain forms a salt bridge to Arg80, which in turn
      interacts with the anion. Replacing either of the salt-bridge partners with an
      alanine reduces repressor activity substantially and it has been inferred that
      the salt bridge could possibly control the wedge angle between the DNA-binding
      domain and the dimerization domain, thereby modulating repressor activity. Cys102
      is a key residue of metal site 2 and its substitution into a serine abolishes
      repressor activity. The crystal structures of Zn-Glu20Ala-DtxR, Zn-Arg80Ala-DtxR,
      Cd-Cys102Ser-DtxR and apo-Cys102Ser-DtxR in two related space groups reveal that
      none of these substitutions leads to dramatic rearrangements of the DtxR fold.
      However, the five crystal structures presented here show significant local
      changes and a considerable degree of flexibility of the DNA-binding domain with
      respect to the dimerization domain. Furthermore, all five structures deviate
      significantly from the structure in the DtxR-DNA complex with respect to overall
      domain orientation. These results confirm the importance of the hinge motion for
      repressor activity. Since the third domain has often been invisible in previous
      crystal structures of DtxR, it is also noteworthy that the SH3-like domain could
      be traced in four of the five crystal structures.

PMID- 11320303
TI  - Caged and clustered structures of endothelin inhibitor BQ123, cyclo(-D-Trp-D-Asp-
      Pro-D-Val-Leu-)-Na+, forming five and six coordination bonds between sodium ions
      and peptides.
AB  - BQ123 is a cyclic pentapeptide and a potent endothelin-1 inhibitor. The crystal
      structure of the BQ123 sodium salt was determined as the first example of an
      endothelin inhibitor. Four independent molecules and many solvent molecules were
      found in the asymmetric unit; the total weight was about 3000 Da. The precise
      structure including the solvent molecules was determined using high-resolution
      data collected on a synchrotron source. Sodium ions formed unique structures with
      five and six coordination bonds and their forms were distinguished into three
      classes. An ion was sandwiched by two BQ123 molecules. This peptide-sodium (2:1)
      complex showed a cage-like structure and octahedral coordination was observed.
      Sodium ions also formed a cluster composed of hydrated water molecules and
      peptides. Two sodium ions were contained in this cluster, making five
      coordination bonds. Despite having the same coordination numbers, these ions were
      distinguishable by differences in the polyhedra. One was trigonal bipyramidal
      (having six planes) and the other was square pyramidal (having five planes). Both
      shapes were very similar to each other, although the synchrotron data clearly
      revealed slight geometrical differences.

PMID- 11320304
TI  - NADP+ and NAD+ binding to the dual coenzyme specific enzyme Leuconostoc
      mesenteroides glucose 6-phosphate dehydrogenase: different interdomain hinge
      angles are seen in different binary and ternary complexes.
AB  - The reduced coenzymes NADH and NADPH only differ by one phosphate, but in the
      cell NADH provides reducing power for catabolism while NADPH is utilized in
      biosynthetic pathways. Enzymes almost invariably discriminate between the
      coenzymes, but glucose 6-phosphate dehydrogenase (G6PD) from Leuconostoc
      mesenteroides is rare in being functionally dual specific. In order to elucidate
      the coenzyme selectivity, the structures of NADP(+)- and NAD(+)-complexed L.
      mesenteroides G6PD have been determined including data to 2.2 and 2.5 A
      resolution, respectively, and compared with unliganded G6PD crystallized in the
      same space groups. Coenzyme binding is also compared with that in a ternary
      complex of a mutant in which Asp177 in the active site has been mutated to
      asparagine. There are no gross structural differences between the complexes. In
      both binary complexes, the enzyme interdomain hinge angle has opened. NADP(+)
      binds to the furthest open form; of the residues within the coenzyme domain, only
      Arg46 moves, interacting with the 2'-phosphate and adenine. NAD(+) is less well
      defined in the binding site; smaller hinge opening is seen but larger local
      changes: Arg46 is displaced, Thr14 bonds the 3'-hydroxyl and Gln47 bonds the 2'
      hydroxyl. In the ternary complex, the hinge angle has closed; only the adenine
      nucleotide is ordered in the binding site. Arg46 again provides most binding
      interactions.

PMID- 11320305
TI  - Ultrahigh-resolution structure of a BPTI mutant.
AB  - The crystal structure of a mutant of bovine pancreatic trypsin inhibitor has been
      refined to 0.86 A resolution using low-temperature synchrotron data. The variant
      contains three mutations in the binding loop (Thr11Ala, Pro13Ala, Lys15Arg) and
      an unrelated Met52Leu substitution. Refinement with anisotropic displacement
      parameters and with removal of main-chain stereochemical restraints converged
      with R = 0.1035. The use of full-matrix refinement provided an estimate of the
      variances in the derived parameters. Some stereochemical parameters, such as the
      planarity of the peptide group and the value of the N-C(alpha)-C angle, show a
      wide spread, suggesting that the standard values used as restraints in protein
      structure refinements may not always be entirely appropriate. Comparison with the
      recently determined room-temperature structure of the same mutant at 1.42 A
      resolution confirms the previous observations and provides new details, such as a
      double conformation of the main chain at Leu29 and at Gly56-Gly57, a high
      proportion (over 20%) of residues in double conformations, correlation of
      disorder through lattice contacts and the positions of H atoms, including those
      in water molecules, and their involvement in C-H...O and N-H...pi hydrogen bonds.

PMID- 11320306
TI  - Structure of Escherichia coli fragment TR2C from calmodulin to 1.7 A resolution.
AB  - Fragment TR2C is the C-terminal part of the calcium-binding protein calmodulin,
      including residues 78-148. The crystal structure of TR2C was solved by molecular
      replacement and refined to a conventional R value of 21.8% (R(free) = 22.0%),
      using all data in the resolution range 20.0-1.7 A. This study shows that the
      secondary structure of TR2C, a pair of EF-hand motifs with two calcium-binding
      sites, is similar to the corresponding motifs in intact calmodulin. However, it
      also indicates that the N-terminus of helix E is closer to the C-terminus of
      helix H in TR2C than in the intact protein and that the loop connecting the EF
      hands shows different conformations in the two structures. The crystal structure
      of TR2C was further found to be similar to the set of NMR structures of this
      fragment, although some pronounced differences exist.

PMID- 11320307
TI  - Structure of cytochrome c7 from Desulfuromonas acetoxidans at 1.9 A resolution.
AB  - Multihaem cytochromes play a key role in electron-transport reactions in the
      periplasm of sulfate- and sulfur-reducing bacteria. The redox proteins grouped in
      the c3 superfamily also display metal-reducing activities, which make them
      interesting biotechnological tools. The crystal structure of the fully oxidized
      cytochrome c7 from Desulfuromonas acetoxidans has been solved by combined
      molecular-replacement and MAD methods. The structure has been refined at 1.9 A
      resolution to an R value of 19.1% (R(free) = 24.3%) and includes three haems and
      116 water molecules. The protein displays the cytochrome c3 fold in a highly
      minimized form, while haem 2 and the surrounding protein environment are missing.
      The geometry of haem packing and of the haem axial ligands and propionates are
      described and compared with that of c3 cytochromes. The crystal structure is
      compared with the solution structure recently obtained by NMR methods and with
      its homologue cytochromes of the c3 superfamily. Comparison of the high number of
      available structures makes it possible to analyze the structural role of the few
      highly conserved residues, in addition to the cysteines and histidines that link
      the porphyrin rings and the Fe atoms to the protein chain.

PMID- 11320308
TI  - Protein crystallization by rational mutagenesis of surface residues: Lys to Ala
      mutations promote crystallization of RhoGDI.
AB  - Crystallization is a unique process that occurs at the expense of entropy,
      including the conformational entropy of surface residues, which become ordered in
      crystal lattices during formation of crystal contacts. It could therefore be
      argued that epitopes free of amino acids with high conformational entropy are
      more thermodynamically favorable for crystal formation. For a protein
      recalcitrant to crystallization, mutation of such surface amino acids to residues
      with no conformational entropy might lead to enhancement of crystallization. This
      paper reports the results of experiments with an important cytosolic regulator of
      GTPases, human RhoGDI, in which lysine residues were systematically mutated to
      alanines. Single and multiple mutations were introduced into two different
      variants of RhoGDI, NDelta23 and NDelta66, in which the first 23 and 66 residues,
      respectively, were removed by recombinant methods. In total, 13 single and
      multiple mutants were prepared and assessed for crystallization and all were
      shown to crystallize using the Hampton Research Crystal Screens I and II, in
      contrast to wild-type NDelta23 and NDelta66 RhoGDI which did not crystallize.
      Four crystal structures were solved (the triple mutants NDelta23:K135,138,141A
      and NDelta66:K135,138,141A, and two single mutants NDelta66:K113A and
      NDelta66:K141A) and in three cases the crystal contacts of the new lattices were
      found precisely at the sites of mutations. These results support the notion that
      it is, in principle, possible to rationally design mutations which systematically
      enhance proteins' ability to crystallize.

PMID- 11320309
TI  - On the routine use of soft X-rays in macromolecular crystallography.
AB  - A diffraction data set has been collected from a blood coagulation factor XIII
      Ca(2+) complex crystal at the X-ray diffraction beamline of the ELETTRA
      synchrotron (Trieste, Italy) at a wavelength of 2.6 A. The data collection could
      be carried out using the beamline as is, without making any time-consuming
      changes to the apparatus. Various data-processing schemes have been employed and
      it has been observed that local or detector scaling procedures are essential for
      producing the 'best' anomalous differences.

PMID- 11320310
TI  - X-LIGAND: an application for the automated addition of flexible ligands into
      electron density.
AB  - With the advent of drug-design experiments where the interaction between a
      protein and a ligand is determined using X-ray crystallography, the use of
      automated methods for modelling the ligand into electron density represents a
      powerful tool. Once the protein structure has been determined by crystallography
      it is normal that subsequent ligand-complex structures are isomorphous, or nearly
      so, with the original structure and it is necessary only to determine the fit of
      ligand to any unsatisfied electron density. The X-LIGAND application was designed
      with this protocol in mind and provides a tool that searches for unsatisfied
      electron density and then fits flexible ligands to this within minutes without
      user intervention.

PMID- 11320311
TI  - Expression, crystallization and preliminary characterization of methylmalonyl
      coenzyme A epimerase from Propionibacterium shermanii.
AB  - Methylmalonyl-CoA epimerase (MMCE) is an enzyme that interconverts the R and S
      epimers of methylmalonyl-CoA in the pathway that links propionyl-CoA with
      succinyl-CoA. This is used for both biosynthetic and degradative processes,
      including the breakdown of odd-numbered fatty acids and some amino acids. The
      enzyme has been expressed in Escherichia coli both as the native enzyme and as
      its selenomethionine (SeMet) derivative. Crystals of both forms have been
      obtained by vapour diffusion using monomethylether PEG 2000 as precipitant. The
      native MMCE crystals are orthorhombic, with unit-cell parameters a = 56.0, b =
      114.0, c = 156.0 A, and the SeMet-MMCE crystals are monoclinic, with unit-cell
      parameters a = 43.6, b = 78.6, c = 89.4 A, beta = 92.0 degrees; both diffract to
      better than 2.8 A resolution.

PMID- 11320312
TI  - Crystallization and preliminary X-ray analysis of cardiotoxic phospholipase A2
      from Ophiophagus hannah (king cobra).
AB  - An acidic phospholipase A2 exhibiting cardiotoxicity, myotoxicity and anti
      platelet activity was isolated from Ophiophagus hannah (king cobra) from Guangxi,
      China. It contains an unusual 'pancreatic loop'. The enzyme was purified to
      homogeneity and crystallized using polyethylene glycol and ethylene glycol as
      precipitants. The crystal belongs to space group C2, with unit-cell parameters a
      = 117.92, b = 62.94, c = 57.16 A, beta = 100.93 degrees. Diffraction data were
      collected to 2.6 A.

PMID- 11320313
TI  - Crystallization and preliminary crystallographic analysis of mannitol
      dehydrogenase (MtDH) from the common mushroom Agaricus bisporus.
AB  - Mannitol dehydrogenase (MtDH) is a key enzyme controlling the reductive synthesis
      of mannitol from fructose in the common mushroom Agaricus bisporus. A better
      understanding of the control of mannitol metabolism can be obtained by studying
      the structure of this enzyme. Here, the purification and crystallization of
      recombinant MtDH are reported. Crystals generally belonged to the space group C2,
      with unit-cell parameters a = 227, b = 125, c = 133 A, beta = 118 degrees, and
      diffracted to at least 1.8 A resolution, although a tantalum derivative belonged
      to the space group P2(1) and diffracted to the lower resolution of 2.9 A.

PMID- 11320314
TI  - Crystallographic characterization of the PDZ1 domain of the human Na+/H+
      exchanger regulatory factor.
AB  - The Na(+)/H(+) exchanger regulatory factor (NHERF) contains two PDZ domains that
      mediate the assembly of transmembrane and cytosolic proteins into functional
      signal transduction complexes. The human NHERF PDZ1 domain, which spans residues
      11-99, interacts specifically with carboxy-terminal residues of the beta2
      adrenergic receptor and the cystic fibrosis transmembrane conductance regulator.
      The NHERF PDZ1 was expressed in Escherichia coli as a soluble protein, purified
      and crystallized in the unbound form using the vapor-diffusion method with 2 M
      ammonium sulfate as the precipitant. Diffraction data were collected to 1.5 A
      resolution using synchrotron radiation. The crystals belong to space group
      P3(1)21 or P3(2)21, with unit-cell parameters a = b = 51.6, c = 58.9 A, and one
      molecule in the asymmetric unit.

PMID- 11320315
TI  - Crystallization and preliminary X-ray diffraction studies of a novel alkaline
      serine protease (KP-43) from alkaliphilic Bacillus sp. strain KSM-KP43.
AB  - A novel alkaline serine protease (KP-43) which belongs to a new class of the
      subtilisin superfamily was crystallized by the sitting-drop vapour-diffusion
      method with ammonium sulfate as a precipitant. The crystals belong to the
      orthorhombic space group C222(1), with unit-cell parameters a = 43.50 (2), b =
      110.4 (1), c = 168.9 (1) A. The crystals diffract X-rays beyond 1.9 A resolution
      using Cu Kalpha radiation from a rotating-anode generator and are suitable for
      high-resolution crystal structure analysis.

PMID- 11320316
TI  - Crystallization and preliminary X-ray crystallographic studies of wild-type human
      ornithine transcarbamylase and two naturally occurring mutants at position 277.
AB  - Wild-type human ornithine transcarbamylase (OTCase) and two mutants (R277Q and
      R277W) that cause 'late-onset' hyperammonemia were crystallized and a preliminary
      structure determination was carried out. The unliganded wild-type enzyme
      crystallizes in the cubic space group I23, with unit-cell parameters a = b = c =
      203.4 A. R277Q crystallizes in two crystal forms under the same crystallization
      conditions. One crystal form is isomorphous to that of unliganded wild-type
      crystals, with unit-cell parameters a = b = c = 202.2 A. The second form also
      belongs to a cubic space group, P4(3)32, but has unit-cell parameters a = b = c =
      139.8 A. R277W crystals are isomorphous to the second crystal form of R277Q, with
      unit-cell parameters a = b = c = 138.7 A. None of these crystal forms is
      isomorphous to other crystal forms of OTCase that have been studied. The
      structures in both crystal forms have been solved using molecular replacement. In
      the first crystal form there are two monomers in the asymmetric unit,
      corresponding to a solvent content of 75%. Because of its high molecular and
      crystal symmetry and the presence of non-crystallographic symmetry, this
      structure could not be solved with AMoRe or X-PLOR, but was solved successfully
      with COMO. There is only one monomer in the asymmetric unit in the second crystal
      form, corresponding to a solvent content of 62%. This structure was successfully
      solved with AMoRe.

PMID- 11320317
TI  - Crystallization and preliminary X-ray analysis of the complex of the epsilon
      subunit and the central domain of the gamma-subunit from the Escherichia coli ATP
      synthase.
AB  - A complex of the epsilon-subunit and the central domain of the gamma-subunit from
      the ATP synthase of Escherichia coli has been purified and crystallized and
      preliminary X-ray analysis has been carried out. The crystals belong to space
      group C222(1), with unit-cell parameters a = 76.7, b = 176.1, c = 67.1 A (at 100
      K). Determination of the structure of this protein complex promises to greatly
      improve the understanding of energy coupling between the F(0) and F(1) sectors
      within the enzyme complex.

PMID- 11320318
TI  - Crystallization and preliminary X-ray analysis of Drosophila glutathione S
      transferase-2.
AB  - The sigma-class glutathione S-transferase-2 (GST-2) from Drosophila melanogaster
      is predominantly found within the indirect flight muscles (IFMs), where it is
      bound to the 'heavy' subunit of the IFM thin filament troponin complex (Tn-H). An
      N-terminal extension found in GST-2 is unique within the sigma GST class and may
      be involved in its interaction with Tn-H or modulate its enzymatic function. The
      recombinant protein has been crystallized at room temperature using ammonium
      sulfate as precipitant. Synchrotron radiation was used to measure a complete
      native data set to 1.75 A resolution from flash-cooled crystals. The crystals
      belong to one of the trigonal space groups P3(1)21 or P3(2)21, with unit-cell
      parameters a = b = 89.7, c = 131.8 A. The self-rotation function is consistent
      with a GST-2 dimer in the asymmetric unit.

PMID- 11320319
TI  - Crystallization and preliminary X-ray crystallographic analysis of Escherichia
      coli RbsD, a component of the ribose-transport system with unknown biochemical
      function.
AB  - The Escherichia coli high-affinity ribose-transport system consists of six
      proteins encoded by the rbs operon (rbsD, rbsA, rbsC, rbsB, rbsK and rbsR). Of
      the six components, RbsD is the only one whose function is unknown. In order to
      gain insights into the function of RbsD by structural analysis, we overexpressed
      and crystallized the protein as a first step toward this goal. RbsD was
      overexpressed in E. coli and crystallized using the hanging-drop vapour-diffusion
      method at 296 K. The crystals belong to the monoclinic space group C2, with unit
      cell parameters a = 285.9, b = 92.3, c = 93.3 A, beta = 105.0 degrees. The unit
      cell is likely to contain 64 molecules of RbsD, with a crystal volume per protein
      mass (V(M)) of 2.43 A(3) Da(-1) and a solvent content of about 49.3% by volume.
      An equilibrium centrifugation analysis demonstrated that RbsD (MW = 15 292 Da)
      exists as an octamer in solution, suggesting that the asymmetric unit contains
      two octameric assemblies of RbsD. A native data set to 2.7 A resolution was
      obtained from a flash-cooled crystal.

PMID- 11320320
TI  - Overexpression, purification, crystallization and data collection of 3
      methylaspartase from Clostridium tetanomorphum.
AB  - 3-Methylaspartase (E.C. 4.3.1.2) catalyses the reversible anti elimination of
      ammonia from L-threo-(2S,3S)-3-methylaspartic acid to give mesaconic acid as well
      as a slower syn elimination from the (2S,3R)-epimer, L-erythro-3-methylaspartic
      acid. The anti-elimination reaction occurs in the second step of the catabolic
      pathway for glutamic acid in Clostridium tetanomorphum. The reverse reaction is
      of particular interest because the addition of ammonia to substituted fumaric
      acids is highly stereoselective and gives highly functionalized amino acids. The
      mechanism of the transformation is unusual and of considerable interest. 3
      Methylaspartase from C. tetanomorphum has been overexpressed and purified from
      Escherichia coli. Crystals of the enzyme have been obtained by sitting-drop
      vapour diffusion. Two native data sets have been collected, one in-house on a
      rotating-anode generator to 3.2 A and one at the European Synchrotron Radiation
      Facility to 2.0 A. A 2.1 A data set has been collected on a crystal of
      selenomethionine protein. Combining the data sets identify the space group as
      P2(1)2(1)2, with unit-cell parameters a = 110.3, b = 109.9, c = 67.2 A, alpha =
      beta = gamma = 90 degrees. The asymmetric unit contains two monomers with 42%
      solvent. A self-rotation function indicates the presence of a twofold axis,
      consistent with a biological dimer.

PMID- 11320321
TI  - Crystallization and preliminary X-ray crystallographic analysis of FlhD/FlhC
      complex from Escherichia coli.
AB  - The heterotetrameric (C(2)D(2)) FlhD/FlhC complex was first discovered as a
      transcriptional activator of the flagellar genes in Escherichia coli. Recent
      studies now show that FlhD/FlhC also regulates several non-flagellar target genes
      in E. coli. The FlhD/FlhC complex also plays several important roles in other
      microorganisms. The molecular interactions between FlhD and FlhC, as well as the
      mechanisms by which the complex may vary its DNA-binding specificity, are not
      clear. Determination of the FlhD/FlhC crystal structure will provide insight into
      these protein-protein and protein-DNA interactions. The initial steps in this
      investigation are reported here: the overexpression, purification and
      crystallization of the FlhD/FlhC complex, the characterization of this crystal
      form and the recording and processing of an initial diffraction data set. The
      obtained crystal form of the FlhD/FlhC complex is hexagonal (space group P6(1),
      unit-cell parameters a = b = 150.5, c = 115.9 A). The crystal density is very low
      (V(M) = 5.5), with 81.7% of its volume occupied by solvent. A single C(2)D(2)
      tetramer is present in the crystallographic asymmetric unit. A complete native
      data set has been collected to 4.5 A resolution.

PMID- 11320322
TI  - Purification, crystallization and preliminary X-ray analysis of two crystal forms
      of ribonuclease Sa3.
AB  - RNase Sa3 produced by Streptomyces aureofaciens strain CCM 3239 belongs to the T1
      family of microbial ribonucleases. It is closely related both to RNase Sa,
      studied in detail earlier, and to RNase Sa2 produced by the same microorganism.
      The most important property of RNase Sa3 is the relatively high cytotoxic
      activity, which was not observed for RNase Sa and Sa2. Recombinant RNase Sa3 was
      overexpressed in Escherichia coli and purified to high homogeneity. The hanging
      drop vapour-diffusion method was used for crystallization. The two crystal forms
      are trigonal P3(1)21 and tetragonal P4(1)2(1)2, with unit-cell parameters a = b =
      64.7, c = 69.6 A, gamma = 120 degrees and a = b = 34.0, c = 147.2 A,
      respectively. They diffract to 2.0 and to 1.7 A resolution, respectively, using
      synchrotron radiation. The asymmetric units of crystal forms I and II contain one
      molecule of the enzyme, which corresponds to V(M) = 3.8 A(3) Da(-1) with a
      solvent content of 68% and V(M) = 1.9 A(3) Da(-1) with a solvent content of 37%,
      respectively.

PMID- 11320323
TI  - Purification, crystallization and preliminary X-ray investigation of the complex
      of human vitamin D binding protein and rabbit muscle actin.
AB  - The vitamin D binding protein binds globular actin with high affinity and is
      involved in the clearance of actin from the blood circulation. A complex of the
      human vitamin D binding protein and rabbit muscle actin was subjected to
      purification steps. The pure complex was crystallized using the hanging-drop
      vapour-diffusion procedure. The best obtained crystals belong to the monoclinic
      space group P2(1), with unit-cell parameters a = 74.44, b = 74.90, c = 88.02 A,
      beta = 110.19 degrees. A complete data set to 2.4 A was collected from a single
      crystal using synchrotron radiation at DESY, Hamburg, Germany.

PMID- 11320324
TI  - Crystallization and preliminary characterization of crystals of the C-terminal
      half fragment of tropomodulin.
AB  - Tropomodulin (40 kDa) stabilizes the actin-tropomyosin filament by capping the P
      end (slow-growing end). The C-terminal half (C20, 20 kDa), an independently
      folded domain that is believed to be responsible for the P-end capping, has been
      crystallized. Crystals grew in the presence of Zn(2+) as the solution pH was
      increased from 3 towards the pI of the protein. The crystals belong to the
      trigonal space group R3. They have unit-cell parameters a = b = 69.6, c = 101.3 A
      (mean values, with a estimated standard deviation of 0.009 A) and diffract to 1.9
      A resolution when the frozen crystals were measured at 120 K on a rotating-anode
      X-ray source at 120 K.

PMID- 11320325
TI  - Crystallization and preliminary X-ray diffraction studies of the epsilonzeta
      addiction system encoded by Streptococcus pyogenes plasmid pSM19035.
AB  - The proteins encoded by the Streptococcus pyogenes broad-host range and low copy
      number plasmid pSM19035 form a toxin-antitoxin module that secures stable
      maintenance by causing the death of plasmid-free segregants. The epsilonzeta
      protein complex was crystallized in four different forms at pH 5.0 and pH 7.0
      using the vapour-diffusion method with PEG 3350 and ethylene glycol as
      precipitants. Three of the crystal forms were obtained in the same droplet under
      identical conditions at pH 5.0. One form belongs to the enantiomorphic space
      groups P4(3)2(1)2 or P4(1)2(1)2. For the other two, the X-ray reflection
      conditions match those of space group P2(1)2(1)2(1), one representing a
      superlattice of the other. A crystal form growing at pH 7.0 also belongs to space
      group P2(1)2(1)2(1), but there is no indication of a structural relationship to
      the other orthorhombic forms. Initially, the crystals diffracted to 2.9 A
      resolution and diffracted to 1.95 A after soaking at pH 7.0. A preparation of
      selenomethionyl epsilonzeta protein complex yielded single crystals suitable for
      X-ray diffraction experiments using synchrotron sources.

PMID- 11320326
TI  - Cloning, expression, purification and preliminary X-ray crystallographic studies
      of yeast Hsp40 Sis1 complexed with Hsp70 Ssa1 C-terminal lid domain.
AB  - Heat-shock protein 70 (Hsp70) plays essential roles in a number of cellular
      processes such as protein folding, assembly and translocation. Heat-shock protein
      40 (Hsp40) transiently interacts with Hsp70 and facilitates Hsp70 functions in
      these processes within cells. Hsp40 recognizes and binds non-native polypeptide
      and delivers it to Hsp70. Hsp40 can then stimulate the ATPase activity of Hsp70
      to refold the polypeptide. To investigate the molecular mechanism by which Hsp40
      interacts with Hsp70 to transport the non-native polypeptide, Saccharomyces
      cerevisiae Hsp40 Sis1 C-terminal peptide-binding fragment complexed with Hsp70
      Ssa1 C-terminal lid domain has been produced and crystallized. The complex
      crystals diffract to 3.3 A and belong to the space group P4(1)2(1)2 or
      P4(3)2(1)2, with unit-cell parameters a = 112.17, c = 171.31 A. Structure
      determination by the MAD method is under way.

PMID- 11320327
TI  - How the CO in myoglobin acquired its bend: lessons in interpretation of
      crystallographic data.
AB  - Contrary to the expectation of chemists, the first X-ray structures of carbon
      monoxide bound to myoglobin (Mb) showed a highly distorted Fe-C-O bond system.
      These results appeared to support the idea of a largely steric mechanism for
      discrimination by the protein against CO binding, a lethal act for the protein in
      terms of its physiological function. The most recent independently determined
      high-resolution structures of Mb-CO have allowed the 25 year old controversy
      concerning the mode of CO binding to be resolved. The CO is now seen to bind in a
      roughly linear fashion without substantial bending, consistent with chemical
      expectations and spectroscopic measurements. Access to deposited diffraction data
      prompted a reevaluation of the sources of the original misinterpretation. A
      series of careful refinements of models against the data at high (1.1 A) and
      modest resolutions (1.5 A) have been performed in anisotropic versus isotropic
      modes. The results suggest that the original artifact was a result of lower
      quality crystals combined with anisotropic motion and limited resolution of the
      diffraction data sets. This retrospective analysis should serve as a caution for
      all researchers using structural tools to draw far-reaching biochemical
      conclusions.

PMID- 11320328
TI  - Structure of the macrocycle thiostrepton solved using the anomalous dispersion
      contribution of sulfur.
AB  - The structure of a tetragonal crystal form of thiostrepton has been solved using
      the anomalous dispersive effects of five S atoms from high-redundancy data
      collected to 1.33 A resolution at the Cu Kalpha wavelength. Data measured to 1.02
      A resolution with a synchrotron source were used for refinement. Details of the
      molecular structure, intramolecular and intermolecular interactions are given.

PMID- 11320329
TI  - Post-translational modification of the N-terminal His tag interferes with the
      crystallization of the wild-type and mutant SH3 domains from chicken src tyrosine
      kinase.
AB  - Structural studies of the wild type and mutants of the src SH3 domain were
      initiated to elucidate the correlation of the native-state topology with protein
      thermostability and folding kinetics. An extra mass of 178 Da arising from the
      post-translational modification at the N-terminal His tag was observed. The
      spontaneous alpha-N-6 gluconoylation at the amino group of the His-tagged SH3
      domain contributed to the observed extra mass. The partial modification of the N
      terminal His-tag produced heterogeneity, both in size and in charge, in the
      Escherichia coli expressed SH3 domain. The removal of the His tag from the SH3
      domain was essential for the crystallization of both wild-type and mutant src
      SH3. Both the wild type and the W43I mutant were crystallized by hanging-drop
      vapor diffusion and are in the hexagonal space group P6(5)22 with one molecule in
      the asymmetric unit. Data sets were collected to 1.8 and 1.95 A resolution for
      the the wild type and the W43I mutant, respectively.

PMID- 11320330
TI  - Effects of different post-crystallization soaking conditions on the diffraction
      of Mtcp1 crystals.
AB  - The crystal structure of human Mtcp1 was determined at 2 A resolution after the X
      ray diffraction limit was improved by post-crystallization soaking in 2.0 M
      ammonium sulfate for 1-5 months. The effects of varying the ammonium sulfate
      concentration and addition of polyethylene glycol to the soaking solution were
      examined in order to understand the phenomenon and to reduce the soaking time.
      Soaking the crystal for one week in a solution of 1.5 M ammonium sulfate and 2%
      PEG 3400 gave the desired improvement in diffraction quality. Therefore,
      different soaking conditions should be explored when crystals show disordered and
      low-resolution diffraction.

PMID- 11320331
TI  - [Developments in anti-malaria agents: chemical data, structure-activity
      relationships].
AB  - Various features of the evolution of a few antimalarial drugs including
      amodiaquine, dihydrofolate-reductase inhibitors, and artemisinin are described.
      The mechanism of action of artemisinin is detailed to explain the information of
      the main metabolites and drug design of certain compounds. Structure-activity and
      structure-neurotoxicity relations are reported. A few examples of cyclic
      peroxycetal synthesis are given. Finally, trends in new and novel compounds are
      presented.

PMID- 11320332
TI  - [Molecular aspects of chloroquine and antifols resistance in P. falciparum].
AB  - Drug resistant malaria is mostly due to Plasmodium falciparum, a species highly
      prevalent in tropical Africa, Amazon and Southeast Asia. P. falciparum is
      responsible for severe involvement of fever or anaemia prompting more than a
      million deaths per year. The emergence of chloroquine resistance has been
      associated with a dramatic increase in malaria mortality in some human
      populations from endemic regions. Rationale for chemoprophylaxis is becoming week
      as multiple drug resistance against well tolerated drugs develops. Plasmodium
      falciparum drug resistant malaria originate from chromosomal mutations. Analysis
      using molecular, genetic and biochemical approaches has shown that
      Epidemiological studies have established that the frequency of chloroquine
      resistant mutants varies among parasites isolates populations while resistance to
      antifolinics is highly prevalent in most malarial endemic countries. An
      established and strong drug pressure and a low antiparasitic immunity probably
      explains the multidrug-resistance encountered in forests of Southeast Asia and
      South America. In Africa, frequent genetic recombinations in Plasmodium originate
      from a high level of malaria transmission, and falciparum chloroquine-resistant
      prevalence seems to stabilise at an equal level as chloroquine-sensitive malaria.
      Nevertheless, resistance levels may differs according to places and time. In vivo
      and in vitro tests are insufficient to give an accurate map of resistance.
      Biochemical tools at a low cost are urgently needed for a prospective monitoring
      of resistance.

PMID- 11320333
TI  - [Malaria, genetics and molecular biology: myths, hopes and realities].
AB  - In the last two decades, progress in molecular biology has revealed a
      considerable genetic diversity among several parasitic species and especially in
      Plasmodium falciparum. This variability is of course facilitated by the haploid
      state of all plasmodial stages present in the human organism. Demonstrating this
      has lead to great progress in understanding some of the great epidemiological,
      pathophysiological, or therapeutic problems raised by malaria. The therapeutic
      aspects, especially those concerning resistance to antimalarials, will be
      presented elsewhere. We will deal only the following questions Several studies,
      some of which are very recent, partially answer these questions and our expertise
      should considerably increase with the future full sequencing of the Plasmodium
      falciparum genome. These observations are of considerable interest but should not
      be over estimated. Indeed, the structure of a genome does not reflect all the
      aspects of biological reality and it will be long and difficult to establish a
      correspondence between plasmodial genotypes and the features of a parasitic
      disease for which there is no true experimental model. Furthermore, the host
      parasite relationships are of course not unifactorial and do not limit themselves
      to the parasite's features. Ecological and ethiological parameters, as well as
      the anophele's vector capacity, the human genetic predisposition for receptivity
      or sensitivity to malaria, and specific or non-specific immune phenomena all play
      a role. Possible interactions with co-infecting micro-organisms, whether viruses
      (CMV, HIV), or other parasites of the same genus (Plasmodiumvivax), or even other
      strains of the same parasitic species (Plasmodium falciparum) may also be of
      crucial importance

PMID- 11320334
TI  - [Conclusion. Malaria 2000: synopsis and perspectives].

PMID- 11320335
TI  - [Human plasma paraoxonase (HuPON1): an anti-atherogenic enzyme with
      organophosphate hydrolase activity].
AB  - Human plasma paraoxonase (PON1) is a calcium-dependent organophosphate-hydrolase.
      In plasma, PON1 is bound to high-density lipoproteins (HDL). PON1 prevents the
      oxidation of LDL and scavenges oxidized phospholipids, thus protecting from
      atherogenesis. Improving the prophylaxis and treatment of organophosphate (OP)
      poisoning is a public health concern that also interests the civilian safety and
      the military. In this context, engineering and formulation of enzymes able to
      scavenge or hydrolyze OPs, such as PON1, are widely studied. Determination of the
      PON1 three-dimensional structure is a key step toward improvement of the enzyme
      functional properties.

PMID- 11320336
TI  - [Principal constituents from flowering aerial parts of wild pansy].
AB  - Dried flowering aerial parts of 12 harvested batches and 9 batches of commercial
      origin from Viola arvensis Murray were examined. The levels of principal
      compounds averaged respectively: total flavonoids 2.86 and 1.63%, rutin 1.15 and
      0.57%, violanthin 0.80 and 0.82%, violarvensin 0.75 and 0.20%, mucilage 21.5 and
      16.5%, total ashes 10.6 and 14.8%, potassium 2.75 and 2.85% and also salicy lic
      acid 0.11 and 0.09%. Saponins were not detected. Specifications were discussed
      for an European Pharmacopoeial monography.

PMID- 11320337
TI  - [Appraisal of fungistatic and fungicidal activities of quaternary compounds
      towards yeasts belonging to the genera Candida and Cryptococcus].
AB  - The fungistatic and fungicidal activities of five quaternary ammonium compounds
      towards Candida and Cryptococcus strains were determined using a bacteriological
      method adapted to mycological experiments. It could be deduced from this study
      that Cryptococcus in spite of the capsule around the cell were more sensitive
      than Candida and that the benzethonium chloride (BC) exhibited the most effective
      action against the whole yeasts. No resistance appeared, only Cryptococcus strain
      was less sensitive than the others.

PMID- 11320338
TI  - [Evaluation of the quality drug prescription for patients to be discharged from a
      university teaching hospital: statutory aspects].
AB  - The aim of this work was to assess the quality of written drug prescriptions for
      patients to be discharged from our hospital. The pharmacological pertinence was
      not evaluated. Each statutory mention was noted according to a binary system:
      1=mention present, 0=mention not present. The total note after analysis of 308
      drug prescriptions was 7.3 +/- 1.3 (3.3-10) for a 3.1 +/- 1.0 (1-10) for each
      prescription. Concerning the "physician" note, the average was 8.1 +/- 1.8.
      Nevertheless, the function and the name were quite ofently omitted (1/2 and 1/3
      respectively). The lowest note was obtained for mentions relating to the patient
      [5.8 +/- 2.0 (0-10)]. The age and the name were omitted (9/10 and 1/10
      respectively). The "drug" note was closed to total note and represented 7.5 +/-
      1.8 (2-10). The detailed analysis showed that 1.8% of drug prescriptions
      presented an illegible drug name. The dosage form was not specified (1/2), the
      galenic form (1/3), the schedule (1/3) and the posology (1/5). These omissions
      did not have any serious repercussion as they were rectified in futher control
      steps. Nevertheless, educational and corrective measures could be aimed to
      improve the drug prescription.

PMID- 11320339
TI  - [New pyrrolo-pyrimidine derivatives with antifungal or antibacterial properties
      in vitro].

PMID- 11320340
TI  - Application of mesenchymal stem cells in the regeneration of musculoskeletal
      tissues.
AB  - Mesenchymal stem cells are a rare population of undifferentiated cells, isolated
      from adult tissue sources, that have the capacity to differentiate into
      mesodermal lineages, including bone, fat, muscle, cartilage, tendon, and marrow
      stroma. These cell populations may be expanded in culture and subsequently
      permitted to differentiate into the desired lineage. This directed
      differentiation may be reached by the application of bioactive molecules,
      specific growth factors, and signaling molecules. Understanding the functional
      potential of these cells and the signaling mechanisms underlying their
      differentiation should lead to innovative protocols for clinical orthopaedic
      interventions. Clinically applicable techniques to isolate, expand, and reimplant
      these autogenous cells will become part of the repertoire of orthopaedic therapy.
      In the presence of extrinsic signaling molecules, provided by both the clinician
      and the local cellular environment, the intrinsic multipotential nature of the
      stem cells may be realized for applications such as the replacement of bone graft
      for segmental defects, nonunions, and spinal fusions. Additional applications may
      include treatment of full-thickness articular defects and articular resurfacing
      by site-specific delivery of stem cells. The ultimate goal is directed cellular
      regeneration of damaged or diseased musculoskeletal tissue. Currently, the
      limitation is our knowledge and ability to direct this differentiation, but with
      further study molecular orthopaedic interventions should become a reality.

PMID- 11320342
TI  - Therese Hidalgo, RN, FNP; proud to be a nurse; Belen, New Mexico.

PMID- 11320341
TI  - Analysis of the marketing provisions of the HIPAA privacy rules.

PMID- 11320343
TI  - Inability of an "energy transfer diagnostician" to distinguish between fertile
      and infertile women.
AB  - CONTEXT: Various forms of "energy healing" have become popular in the United
      States. OBJECTIVE: To test the assertion that an energy healer can, without
      physical contact, distinguish the presence or absence of internal organ pathology
      in individuals who lack overt physical findings. DESIGN: Observational randomized
      study, in which we tested the assertion by a well-recognized alternative healer
      that he had particular skill in using energy transfer to detect the presence or
      absence of fertility disorders in women. PATIENTS: Convenience sample of 37
      women, 28 of whom had documented pathology resulting in infertility, and 9 of
      whom were fertile. OUTCOMES: The healer was provided with no medical history and
      performed diagnostic evaluations without physical contact with the blindfolded,
      clothed, and silent subjects. We compared to random chance the ability of the
      healer to establish a diagnosis of fertility or fertility disorder. SETTING:
      Teaching hospital. MAIN RESULTS: The healer was unable to distinguish the
      presence or absence of fertility disorders in the study subjects. CONCLUSION:
      This study points to further need for fair yet rigorous assessment of claims that
      energy transfer can lead to accurate clinical diagnoses.

PMID- 11320344
TI  - National serologic survey of measles immunity among persons 6 years of age or
      older, 1988-1994.
AB  - CONTEXT: Measles incidence in the United States is at a record low, and
      indigenous transmission has been interrupted in each year since 1996, suggesting
      that measles is no longer endemic. A national estimate of measles immunity and an
      understanding of predictors of measles susceptibility are essential for assuring
      sustained elimination of endemic disease. OBJECTIVE: To assess patterns of
      immunity and to determine predictors of susceptibility to measles.
      DESIGN/SETTING: Sera and data on participants from the third National Health and
      Nutrition Examination Survey (1988-1994) (NHANES III) were examined. NHANES III
      was a cross-sectional survey of a representative sample of the civilian,
      noninstitutionalized population of the United States. POPULATION: 20,100 persons
      6 years of age or older were tested for measles-specific immunoglobulin G (IgG)
      antibody by an enzyme immunoassay. MAIN OUTCOME MEASURE: Participants with serum
      positive for measles antibody were considered protected or immune to measles
      disease. RESULTS: Prevalence of measles immunity was 93%. Nearly all persons
      (99%) born in the prevaccine era (before 1957) were immune. Immunity declined
      among persons born in the vaccine era (after 1956) to 81% among those born in
      1967-1976, and increased again to 89% among those born in 1977-1988. Among
      persons born in the vaccine era, independent predictors of measles susceptibility
      varied by birth cohort and included birth in the United States, residence in a
      noncrowded household, residence in a nonmetropolitan area, and, among males, non
      Hispanic white and Mexican American race/ethnicity. Among adults 17 years of age
      or older, additional predictors of susceptibility included living at or above the
      poverty line and not currently being married. CONCLUSIONS: Population immunity
      among persons 6 years of age or older is very high; however, as many as 15
      million persons across the United States may lack humoral immunity. While it is
      unclear that the susceptible population can support continuous, indigenous
      transmission of measles, providers should follow current recommendations to
      evaluate the measles susceptibility of patients born in the vaccine era and
      vaccinate eligible patients.

PMID- 11320345
TI  - Neil Calman, MD; urban warrior; New York, New York.

PMID- 11320346
TI  - Addressing postmenopausal estrogen deficiency: a position paper of the American
      Council on Science and Health.
AB  - During the past century, Medicine has made immense strides toward improving the
      general health, so much so that it now claims dominion over many events that were
      once perceived as immutably natural. In the case of postmenopausal estrogen
      replacement therapy (ERT), it is not clear that the public has entirely accepted
      Medicine's mandate. Despite cogent arguments for adopting a long-term regimen of
      prophylaxis for estrogen deficiency-related problems, relatively few women have
      received sustained treatment. Medical providers will be more effective advocates
      of long-term estrogen therapy by becoming more conversant with its effects and
      proficient in its application. This review aims to provide readers with a
      foundation in estrogen physiology and pharmacology that will enhance present
      therapeutic efforts and facilitate a critical appraisal of new regimens as they
      become available.

PMID- 11320347
TI  - Letter in Response to: Words that are not spoken: An inside look at the African
      AIDS crisis.

PMID- 11320349
TI  - A perinatal pathology view of preterm labor.
AB  - The development and widespread use of tocolytic agents over the past 2 decades
      has not appeared to substantially affect the overall incidence of preterm
      delivery in the United States. Preterm delivery, therefore, remains one of the
      most poorly controlled and poorly understood mechanisms of perinatal morbidity
      and mortality and a significant strain on public health resources. The purpose of
      this review is to examine what is currently understood about the clinical
      manifestations and indicators of preterm delivery, and what, if any, may be the
      contribution of placental pathology to the understanding of the structural and
      functional abnormalities that may precede these clinical signs. Two case studies
      will be used to show how placental pathology may document a pattern of
      reproductive failure that eludes current methods of clinical screening. A
      retrospective analysis of what may have gone wrong in the pregnancies, focusing
      on the placental lesions, may contribute to a greater understanding of the
      heterogeneous overall processes behind recurrent idiopathic preterm delivery.
      Such analysis, in conjunction with known clinical factors, may guide the
      development of better-directed diagnostics and therapies.

PMID- 11320350
TI  - Rationale and technique of clinical breast examination.
AB  - Despite the advances in breast imaging, there are clear indications for the need
      of clinical breast examination as part of breast cancer screening for all women.
      The article reviews the technique for clinical breast examination and assessment
      of its results. The main goal of the clinical breast examination is to
      differentiate normal physiologic nodularity from a discrete breast mass. If a
      discrete mass is identified, evaluation is mandatory in all cases to exclude
      breast cancer. This evaluation is guided by the features of the clinical
      findings, the age of the woman, and her personal risk for breast cancer.

PMID- 11320351
TI  - Addressing intimate partner violence in primary care practice.
AB  - Primary care practice provides an ideal opportunity for the discussion of the
      remarkably prevalent yet often hidden problem of intimate partner violence.
      Patients report that screening of intimate partner violence is acceptable, yet
      most providers do not discuss intimate partner violence with their patients. The
      purpose of this article is 3-fold: to outline what is known about the prevalence
      and health effects of intimate partner violence and why providers should discuss
      intimate partner violence with their patients, to review recommended screening
      policy and how to ask about and intervene in cases of intimate partner violence,
      and finally to provide suggestions for institutionalizing a clinical response to
      intimate partner violence.

PMID- 11320352
TI  - Optimal procedure for extracting RNA from human ocular tissues and expression
      profiling of the congenital glaucoma gene FOXC1 using quantitative RT-PCR.
AB  - PURPOSE: To develop methods for obtaining high quality RNA from human donor eyes
      and to determine the expression profile of the congenital glaucoma gene FOXC1 in
      human ocular tissues. METHODS: To obtain high quality RNA from donor eyes,
      several different preservation methods were tested including storing eyes on ice,
      freezing eyes, and placing eyes in the commercial fixative RNAlaterTM prior to
      dissection and RNA extraction. Nine different ocular tissues from human donors
      were dissected and examined. Pigment-free total RNA was isolated and used for
      quantitative real-time RT-PCR using FOXC1 and GAPDH (internal standard) primers
      to assess the quality and expression of FOXC1. RESULTS: An expression profile of
      FOXC1 in human ocular tissues was determined using quantitative PCR of RNA
      isolated using a simple and effective procedure for ocular tissue preservation
      and pigment-free RNA isolation. Higher quality RNA was obtained from human donor
      eyes preserved in RNAlaterTM compared to RNA extracted from eyes stored on ice or
      frozen at -80 degrees C. RNA extraction techniques that removed interfering
      pigment from ocular tissues produced RNA that could be easily amplified by PCR.
      In the adult human eye, expression of FOXC1 was greatest in the trabecular
      meshwork (TM) followed by the optic nerve head, choroid/RPE, ciliary body,
      cornea, and iris. FOXC1 expression levels were much lower in other non-ocular
      human tissues, such as liver, muscle, lung, heart, and kidney. CONCLUSIONS: Using
      an optimized donor eye preservation method and tissue RNA isolation procedure, we
      show that the FOXC1 transcription factor gene, which is known to be associated
      with developmental glaucoma, also may have an important role in the adult eye.

PMID- 11320353
TI  - Expression of rhodopsin and arrestin during the light-dark cycle in Drosophila.
AB  - PURPOSE: To determine the protein and transcript levels for rhodopsin (Rh1),
      arrestin 1 (Arr1), and arrestin 2 (Arr2) over a 12 h light/12 h dark cycle in the
      retina of the fruit fly, Drosophila melanogaster. This information is important
      for understanding the process of photoreceptor membrane turnover. METHODS:
      Drosophila were entrained for several generations to a daily 12 h light/12 h dark
      cycle. They were sacrificed at 4 h intervals, beginning at the time of onset of
      the light phase. Proteins were resolved by polyacrylamide gel electrophoresis
      (PAGE) and subjected to immunoblot analysis using antibodies directed to
      rhodopsin, NinaA, Arr1, and Arr2. Northern blots were incubated with riboprobes
      corresponding to the rhodopsin gene (ninaE), arrestin1 (arr1), and arrestin2
      (arr2). RESULTS: In entrained Drosophila, protein and mRNA levels for rhodopsin,
      arrestin1, and arrestin2 were constant during a 12 h light/12 h dark cycle.
      CONCLUSIONS: These results indicate that rhodopsin and arrestin protein synthesis
      in Drosophila photoreceptors do not fluctuate on a daily cycle. These findings
      are similar to those obtained in Xenopus laevis, but in contrast to a variety of
      other vertebrate and invertebrate species.

PMID- 11320354
TI  - Postoperative atrial fibrillation after heart surgery: What are the goals of
      prevention?

PMID- 11320355
TI  - Noninvasive tests of vascular function and structure: why and how to perform
      them.
AB  - BACKGROUND: Early atherosclerosis involves the endothelium of many arteries.
      Information about peripheral arterial anatomy and function derived from vascular
      imaging studies such as brachial artery reactivity (BAR) and carotid intima media
      thickness (IMT) may be pertinent to the coronary circulation. The prevention and
      early treatment of atherosclerosis is gaining more attention, and these tests
      might be used as indications or perhaps guides to the effectiveness of therapy,
      but their application in clinical practice has been limited. This review seeks to
      define the anatomy and pathophysiology underlying these investigations, their
      methodology, the significance of their findings, and the issues that must be
      resolved before their application. METHODS: The literature on BAR and IMT is
      extensively reviewed, especially in relation to clinical use. RESULTS: Abnormal
      flow-mediated dilation is present in atherosclerotic vessels, is associated with
      cardiovascular risk factors, and may be a marker of preclinical disease.
      Treatment of known atherosclerotic risk factors has been shown to improve flow
      mediated dilation, and some data suggest that vascular responsiveness is related
      to outcome. Carotid IMT is associated with cardiovascular risk factors, and
      increased levels can predict myocardial infarction and stroke. Aggressive risk
      factor management can decrease IMT. CONCLUSIONS: BAR and IMT are functional and
      structural markers of the atherosclerotic process. The clinical use of BAR has
      been limited by varying reproducibility and the influence by exogenous factors,
      but IMT exhibits less variability. A desirable next step in the development of
      BAR and IMT as useful clinical tools would be to show an association of
      improvement in response to treatment with improvement in prognosis.

PMID- 11320356
TI  - Infarct artery reocclusion after primary angioplasty, stent placement, and
      thrombolytic therapy for acute myocardial infarction.
AB  - BACKGROUND: The benefits of thrombolytic therapy for acute myocardial infarction
      (AMI) are limited by reocclusion of the infarct-related artery, which occurs in
      25% to 30% of patients after successful reperfusion. The frequency of reocclusion
      after balloon angioplasty and stenting in this setting is less well documented.
      The aim of this study was to analyze the frequency and timing of reocclusion
      after percutaneous transluminal coronary angioplasty (PTCA) and stent placement
      during AMI from all available studies compared with previously published
      reocclusion rates after thrombolysis. METHODS AND RESULTS: The previously
      published thrombolysis data included 4231 patients in 19 studies with > or = 75
      patients. Only PTCA studies with > or = 50 patients and stent studies with > or =
      30 patients, in which routine angiographic follow-up was obtained in > or = 60%
      of patients, were included. Ten PTCA studies with a total of 1943 patients were
      analyzed, with follow-up angiography in 1391 (72%). Reocclusion rates ranged from
      5% to 16.7%. The stent studies included 698 patients from 7 studies, with follow
      up angiography in 92%. Reocclusion rates ranged from 0% to 6%. With the use of
      logistic regression analysis with allowance for overdispersion, there was a
      significantly lower rate of reocclusion after PTCA (odds ratio, 0.38; confidence
      interval, 0.24 to 0.57; P <.0001) and stent placement (odds ratio, 0.11;
      confidence interval, 0.05 to 0.22; P <.0001) compared with thrombolysis.
      Reocclusion after stent placement was lower than after PTCA (odds ratio, 0.28;
      confidence interval, 0.13 to 0.6; P <.0001). CONCLUSIONS: Reocclusion after PTCA
      and stent placement during AMI is less frequent than after thrombolysis. This may
      contribute to the superior outcome of patients treated with PTCA and stent
      placement in this setting.

PMID- 11320357
TI  - INTER-HEART: A global study of risk factors for acute myocardial infarction.
AB  - BACKGROUND: Although declines in mortality rates have occurred in most developed
      countries, increases are being seen in developing countries. Our knowledge of
      risk factors for acute myocardial infarction (AMI) is largely derived from
      studies in the former. Applicability of these results to other populations is
      unknown. The objectives of INTER-HEART are to determine the association between
      risk factors and AMI within populations defined by ethnicity and/or geographic
      region and to assess the relative importance of risk factors across these
      populations. METHODS: INTER-HEART is a study of 14,000 cases of AMI and 16,000
      matched control patients from 46 countries, which was conducted with a
      standardized protocol. Questionnaires were translated into 11 languages; physical
      measurements were obtained, and 20 mL of blood was drawn and shipped frozen to a
      central laboratory in Canada. The study will evaluate the importance of
      conventional and emerging risk factors within each geographic region and whether
      their impact varies by region. RESULTS: INTER-HEART is sponsored by the World
      Health Organization and the World Heart Federation and has received funding from
      several peer-reviewed agencies and many different pharmaceutical companies. A
      vanguard phase (February 1999 to 2000) enrolled 4000 subjects from 41 countries.
      Full data collection started in April 2000 and is expected to be completed by
      October 2002. CONCLUSIONS: Several years of targeted work have allowed the
      development of the concepts that were tested in the pilot studies. This has
      ensured the feasibility of INTER-HEART. This study has the potential to have a
      major impact in developing a worldwide strategy for cardiovascular disease
      prevention, especially in developing countries and nonwhite populations.

PMID- 11320358
TI  - Aggressive versus moderate lipid-lowering therapy in postmenopausal women with
      hypercholesterolemia: Rationale and design of the Beyond Endorsed Lipid Lowering
      with EBT Scanning (BELLES) trial.
AB  - BACKGROUND: Electron beam tomography (EBT) is a noninvasive technique that allows
      the study of the entire coronary artery tree during a brief imaging session
      without the injection of any contrast media. Atherosclerosis is identified
      vicariously through the visualization of coronary calcific deposits. Quantitative
      assessments of calcium burden, such as calcium volume scores, have been shown to
      be a useful means to assess treatment-related changes in the extent of
      atherosclerotic plaques. Historically, the elderly female population has received
      less medical recognition regarding the risk and severity of coronary heart
      disease (CHD). METHODS: In the BELLES (Beyond Endorsed Lipid Lowering with EBT
      Scanning) trial, the presence of asymptomatic CHD in 600 postmenopausal women
      will be assessed by EBT. In this 1-year, multicenter, randomized, double-blind,
      parallel-group study, aggressive lipid-lowering treatment will be compared with
      moderate lipid-lowering treatment in postmenopausal women with
      hypercholesterolemia. The hypothesis we will test is that aggressive lipid
      lowering therapy with 80 mg/d atorvastatin can produce greater reductions in
      atherosclerotic plaque burden as assessed by volumetric calcium scores than a
      moderate treatment with 40 mg/d pravastatin. The primary outcome measure will be
      the percent change from baseline in total CVS determined by EBT at 12 months.
      CONCLUSIONS: The results of the BELLES trial will help assess the actual
      incidence of CHD in postmenopausal women and the relative ability of two
      different lipid-lowering therapies to halt its progression.

PMID- 11320359
TI  - Cost-effectiveness of pravastatin therapy for survivors of myocardial infarction
      with average cholesterol levels.
AB  - BACKGROUND: The objective of this study was to assess the cost-effectiveness of
      pravastatin therapy in survivors of myocardial infarction with average
      cholesterol levels. METHODS: We performed a cost-effectiveness analysis based on
      actual clinical, cost, and health-related quality-of-life data from the
      Cholesterol and Recurrent Events (CARE) trial. Survival and recurrent coronary
      heart disease events were modeled from trial data in Markov models, with the use
      of different assumptions regarding the long-term benefit of therapy. RESULTS:
      Pravastatin therapy increased quality-adjusted life expectancy at an incremental
      cost of $16,000 to $32,000 per quality-adjusted life-year gained. In subgroup
      analyses, the cost-effectiveness of pravastatin therapy was more favorable for
      patients >60 years of age and for patients with pretreatment low-density
      lipoprotein cholesterol levels >125 mg/dL. Results were sensitive to the cost of
      pravastatin and to assumptions about long-term survival benefits from pravastatin
      therapy. CONCLUSIONS: The cost-effectiveness of pravastatin therapy in survivors
      of myocardial infarction with average cholesterol levels compares favorably with
      other interventions.

PMID- 11320360
TI  - Coronary microvascular dysfunction is highly prevalent in women with chest pain
      in the absence of coronary artery disease: results from the NHLBI WISE study.
AB  - BACKGROUND: Chest pain in the absence of obstructive coronary artery disease
      (CAD) is common in women; it is frequently associated with debilitating symptoms
      and repeated evaluations and may be caused by coronary microvascular dysfunction.
      However, the prevalence and determinants of microvascular dysfunction in these
      women are uncertain. METHODS: We measured coronary flow velocity reserve
      (coronary velocity response to intracoronary adenosine) to evaluate the coronary
      microvasculature and risk factors for atherosclerosis in 159 women (mean age,
      52.9 years) with chest pain and no obstructive CAD. All women were referred for
      coronary angiography to evaluate their chest pain as part of the Women's Ischemia
      Syndrome Evaluation (WISE) study. RESULTS: Seventy-four (47%) women had subnormal
      (<2.5) coronary flow velocity reserve suggestive of microvascular dysfunction
      (mean, 2.02 +/- 0.38); 85 (53%) had normal reserve (mean, 3.13 +/- 0.64).
      Demographic characteristics, blood pressure, ventricular function, lipid levels,
      and reproductive hormone levels were not significantly different between women
      with normal and those with abnormal microvascular function. Postmenopausal
      hormone use within 3 months was significantly less prevalent among those with
      microvascular dysfunction (40% vs 60%, P =.032). Age and number of years past
      menopause correlated with flow velocity reserve (r = -0.18, P =.02, and r = 
      0.30, P <.001, respectively). No significant associations were identified between
      flow velocity reserve and lipid and hormone levels, blood pressure, and left
      ventricular ejection fraction. CONCLUSIONS: Coronary microvascular dysfunction is
      present in approximately one half of women with chest pain in the absence of
      obstructive CAD and cannot be predicted by risk factors for atherosclerosis and
      hormone levels. Therefore, the diagnosis of coronary microvascular dysfunction
      should be considered in women with chest pain not attributable to obstructive
      CAD.

PMID- 11320361
TI  - Lower-dose heparin with fibrinolysis is associated with lower rates of
      intracranial hemorrhage.
AB  - BACKGROUND: The optimal heparin dose as an adjunct to fibrinolysis and its role
      in causing intracranial hemorrhage (ICH) is unclear. METHODS: We reviewed the
      heparin regimens and rates of ICH in 3 sets of recent fibrinolytic trials: (1)
      studies with accelerated recombinant tissue plasminogen activator (TPA,
      alteplase) plus intravenous heparin, in which the heparin regimen was changed
      during the course of the trial; (2) phase III trials with accelerated TPA plus
      intravenous heparin; and (3) trials of new single-bolus fibrinolytic agents.
      RESULTS: Lower rates of ICH were observed among studies of accelerated TPA that
      reduced the heparin dose mid-trial (TIMI 9A --> 9B: 1.87% --> 1.07%, GUSTO-IIa -
      > IIb: 0.92% --> 0.71%, TIMI 10B: 2.80% --> 1.16%). Rates of ICH with accelerated
      TPA gradually increased from GUSTO-I (0.72%) in 1990 to 1993 to ASSENT-2 (0.94%)
      in 1997 to 1998. However, this trend was reversed in InTIME-II, which used the
      lowest heparin dose and most aggressive activated partial thromboplastin time
      monitoring and observed an ICH rate of 0.64% with accelerated TPA. Lower ICH
      rates were also observed when the heparin dose was reduced with single-bolus
      tenecteplase (TNK-TPA) and lanoteplase. CONCLUSIONS: Nonrandomized comparisons
      with accelerated TPA suggest that lower doses of intravenous heparin are
      associated with lower rates of ICH. This observation also appears to apply to
      single-bolus TNK-TPA and novel plasminogen activator. A lower-dose, weight
      adjusted heparin regimen (60 U/kg bolus; maximum, 4000 U; 12 U/kg per hour
      infusion; maximum, 1000 U/h) with earlier monitoring of activated partial
      thromboplastin time is currently recommended in the revised American College of
      Cardiology/American Heart Association myocardial infarction guidelines and should
      be used in clinical practice.

PMID- 11320362
TI  - Effects of prolonged strenuous exercise on plasma levels of atrial natriuretic
      peptide and brain natriuretic peptide in healthy men.
AB  - BACKGROUND: Now that marathon racing is growing in popularity, many thousands of
      enthusiastic athletes are participating in various ultramarathons all over the
      world each year. However, it remains controversial whether such a sport
      contributes to the promotion of health. The occurrence of transient cardiac
      dysfunction and irreversible myocardial injury has been reported in association
      with such exercise in healthy individuals. Brain natriuretic peptide (BNP) is a
      cardiac hormone, as is atrial natriuretic peptide (ANP), and its measurement has
      been widely used for clinical evaluation of cardiac dysfunction. However, little
      is known about the response of plasma BNP to prolonged strenuous exercise. We
      hypothesized that confirmation of minimal cardiac dysfunction or myocardial
      injury may be made by measurements of plasma BNP. METHODS: Levels of plasma ANP,
      BNP, catecholamines, blood lactate, and serum cardiac troponin T (cTnT) were
      determined before and after a 100-km ultramarathon in 10 healthy men to examine
      the effects of the exercise on levels of ANP and BNP and correlations between the
      natriuretic peptides and cTnT as a marker for myocardial damage. RESULTS: Whereas
      all variables significantly increased after the race, increased levels of ANP and
      BNP were most strongly correlated with increases in cTnT levels. The cTnT level
      after the race was greater than the upper reference limit in 9 of 10 men.
      CONCLUSIONS: Such exercise significantly increased ANP and BNP levels in healthy
      men, and the increases could be partially attributed to myocardial damage during
      the race.

PMID- 11320363
TI  - Early peak creatine kinase activity is not always a marker of successful
      reperfusion with myocardial salvage in patients with reperfused anterior acute
      myocardial infarction.
AB  - BACKGROUND: Although early peak creatine kinase activity (peak CK) is considered
      a reliable marker of coronary reperfusion in patients with acute myocardial
      infarction (AMI), whether early peak CK indicates good myocardial salvage is
      unclear. Moreover, some patients have late peak CK despite successful
      reperfusion, and its clinical implication remains to be elucidated. METHODS AND
      RESULTS: We examined the association of the time to peak CK with predischarge
      left ventricular function in 124 patients with a first AMI who had successful
      reperfusion within 6 hours from symptom onset. Patients were classified according
      to the time from reperfusion to peak CK: group A, 61 patients with peak CK < 6
      hours; group B, 42 with peak CK from 6 to 12 hours; and group C, 21 with peak CK
      > 12 hours. There were no differences among the 3 groups in age, sex, method of
      reperfusion, time from symptom onset to reperfusion, collateral circulation, or
      the extent of risk area estimated by number of leads with ST-segment elevation.
      Left ventricular ejection fraction measured by predischarge left ventriculography
      was lowest in group A, followed by group B, and highest in group C (median
      values, 43%, 52%, and 60%, P < .01). Left ventricular dysfunction (left
      ventricular ejection fraction < or = 40%) occurred in 26 (43%) patients in group
      A, 8 (19%) in group B, and none in group C (P < .01). CONCLUSIONS: We conclude
      that compared with early peak CK, late peak CK consistently reflects good
      myocardial salvage in patients with anterior AMI who had successful reperfusion
      within 6 hours from symptom onset.

PMID- 11320364
TI  - Depression but not anxiety influences the autonomic control of heart rate after
      myocardial infarction.
AB  - AIMS: It has been previously hypothesized that the adverse outcome observed in
      depressed patients after myocardial infarction might be due to an imbalance in
      autonomic nervous system activity. The aim of this study was to define the role
      of depressive and anxious symptoms in influencing autonomic control of heart rate
      after myocardial infarction. METHODS AND RESULTS: The SD of RR intervals,
      baroreflex sensitivity, and depression and anxiety (Zung's scales) were assessed
      before discharge in 103 patients with acute myocardial infarction; 32 were found
      to be depressed. Among the patients who were not taking beta-blockers, those with
      depression had significantly lower SDs of RR intervals and baroreflex sensitivity
      than did those without depression (96.3 +/- 22.2 ms vs 119.5 +/- 37.7 ms, P
      =.016; 8.6 +/- 6.2 ms vs 11.8 +/- 6.5 ms/mm Hg, P =.01, respectively). No
      differences were found when anxiety was considered or when beta-blockers were
      given. Among the patients not taking beta-blockers, there was a significant
      correlation between depression levels and both the SD of RR intervals (r = -0.47)
      and baroreflex sensitivity (r = -0.40). CONCLUSIONS: In patients with myocardial
      infarction, depression but not anxiety negatively influences autonomic control of
      heart rate. Beta-blockers modify these influences.

PMID- 11320365
TI  - Exercise versus dobutamine-induced ST elevation in the infarct-related
      electrocardiographic leads: clinical significance and correlation with functional
      recovery.
AB  - BACKGROUND: The clinical significance of stress-induced ST elevation early after
      acute myocardial infarction and its relation to functional recovery remain
      controversial. The aims of this study were (1) to determine the incidence of ST
      elevation during dobutamine and exercise tests and (2) to assess the relative
      accuracy of exercise and dobutamine ST elevation for predicting functional
      recovery after acute myocardial infarction. METHODS AND RESULTS: We investigated
      52 patients who underwent supine exercise (from 25 W to maximal charge) and
      dobutamine (from 5 to 40 microg/kg per minute and up to 1 mg atropine) stress
      electrocardiography in the same position. ST elevation was defined as new or
      worsening at >1 mm, 80 ms after J point. Echocardiography and quantitative
      angiography were available in all patients before hospital discharge. The follow
      up resting echocardiogram was recorded 30 +/- 6 days after the acute event. ST
      elevation developed during 30 (58%) dobutamine and 24 (46%) exercise tests. The
      sum of ST elevation was higher during dobutamine testing (7.7 +/- 3.8 mm) than
      during exercise (5.5 +/- 2.5 mm) (P =.03). A low peak creatine kinase level was
      the single independent predictor of dobutamine-induced ST elevation. Functional
      improvement occurred in 35 patients. Two independent predictors of functional
      recovery were selected from multivariate analysis: dobutamine ST elevation
      (chi(2) = 9.1; P =.0026) and low peak creatine kinase level (chi(2) = 5.1; P
      =.025). When dobutamine ST elevation was not included in multivariate analysis,
      exercise-induced ST elevation emerged as an independent predictor of functional
      recovery (chi(2) = 5.0; P =.023). Significant linear correlation was found
      between the sum of ST elevation at peak dobutamine stress and the extent of
      functional recovery (r = 0.87; P <.0001). In contrast, no correlation was
      observed with exercise ST elevation (r = 0.06; P = not significant). CONCLUSIONS:
      Stress-induced ST elevation is an ancillary sign of viable myocardium that can
      recover. The sum of ST elevation at peak dobutamine stress correlates with the
      extent of functional recovery.

PMID- 11320366
TI  - Anti-human skeletal muscle glycolipid antibodies in unstable angina.
AB  - BACKGROUND: We studied whether the level of anti-skeletal muscle glycolipid
      antibodies (AGA), a marker of acute rejection in heart transplantation, may be
      associated with an adverse prognosis in unstable angina. METHODS AND RESULTS: The
      in-hospital evolution of 50 patients with unstable angina (Braunwald class III B)
      was assessed. We determined the incidence of death, myocardial infarction, and
      refractory angina. Blood was collected at admission and 24 hours later for
      determination of AGA levels by enzyme-linked immunosorbent assay. Twenty-three
      patients showed a decrease in the AGA level at 24 hours after admission. Ten in
      hospital cardiac events occurred in these patients (43.4%) as compared with 4
      (14.8%) in the 27 patients who did not show a decrease (P =.025). In patients
      with previous myocardial infarction (n = 26), the AGA assay was a powerful
      predictor of outcome. In this subgroup, 66.6% of patients who had decreased AGA
      levels (8 of 12) had cardiac events as compared with 14.2% (2 of 14) of those who
      did not have that decrease (P =.001). CONCLUSIONS: We conclude that a decrease of
      AGA levels 24 hours after admission is associated with a complicated in-hospital
      course. This finding may provide new insights in the phenomenon of plaque
      instability involved in the development of acute coronary syndromes.

PMID- 11320367
TI  - Left ventricular function and hemodynamic features of inappropriate left
      ventricular hypertrophy in patients with systemic hypertension: the LIFE study.
AB  - BACKGROUND: Predicted left ventricular (LV) mass for sex, height (2.7), and
      hemodynamic load can be used as an intrapatient reference for the observed LV
      mass. The ratio of observed/predicted LV mass may allow more physiologically
      correct comparisons of LV geometry, systolic and diastolic functions, and
      hemodynamics among hypertensive patients. METHODS: We studied 659 participants in
      the LIFE (Losartan Intervention for Endpoint Reduction in Hypertension) study
      with both electrocardiographic and echocardiographic LV hypertrophy (68% of the
      echocardiographic cohort) without previous myocardial infarction. LV mass was
      predicted by an equation including sex, stroke work, and height (2.7).
      Observed/predicted LV mass > 128% defined inappropriate LV hypertrophy (iLVH).
      Relative wall thickness > or = 0.43 defined concentric LV geometry. Systolic
      myocardial dysfunction was assessed by midwall mechanics and abnormal LV
      relaxation by isovolumic relaxation time (IVRT). RESULTS: Compared with patients
      with appropriate LV hypertrophy (aLVH), those with iLVH had higher body mass
      index, LV mass index, relative wall thickness, prevalences of systolic myocardial
      dysfunction and prolonged IVRT and lower end-systolic stress and cardiac index.
      Patients with eccentric iLVH had the highest wall stress and lowest ejection
      fraction; 43% had systolic myocardial dysfunction. Of patients with concentric
      iLVH, 79% had systolic myocardial dysfunction but normal ejection fraction and
      the lowest wall stress. Systolic myocardial dysfunction was present in 12% with
      concentric aLVH and none with eccentric aLVH. Prevalence of prolonged IVRT was
      high in all 4 groups (65% to 77%). Cardiac index was similarly lower with
      concentric or eccentric iLVH than with aLVH. CONCLUSIONS: Among hypertensives
      with LV hypertrophy, iLVH identified cardiac phenotypes with a high prevalence of
      myocardial systolic dysfunction.

PMID- 11320368
TI  - Uric acid in cachectic and noncachectic patients with chronic heart failure:
      relationship to leg vascular resistance.
AB  - BACKGROUND: Chronic heart failure (CHF) is a hyperuricemic state, and capillary
      endothelium is the predominant site of xanthine oxidase in the vasculature.
      Upregulated xanthine oxidase activity (through production of toxic free radicals)
      may contribute to impaired regulation of vascular tone in CHF. We aimed to study
      the relationship between serum uric acid levels and leg vascular resistance in
      patients with CHF with and without cachexia and in healthy control subjects.
      METHODS: In 23 cachectic and 44 noncachectic patients with CHF (age, 62 +/- 1
      years, mean +/- SEM) and 10 healthy control subjects (age, 68 +/- 1 years), we
      assessed leg resting and postischemic peak vascular resistance (calculated from
      mean blood pressure and leg blood flow by venous occlusion plethysmography).
      RESULTS: Cachectic patients, compared with noncachectic patients and control
      subjects, had the highest uric acid levels (612 +/- 36 vs 459 +/- 18 and 346 +/-
      21 micromol/L, respectively, both P <.0001) and the lowest peak leg blood flow
      and vascular reactivity (reduction of leg vascular resistance from resting to
      postischemic conditions: 83% vs 88% and 90%, both P <.005). In all patients,
      postischemic vascular resistance correlated significantly and independently of
      age with uric acid (r = 0.61), creatinine (r = 0.47, both P <.0001), peak VO2 (r
      = 0.34), and New York Heart Association class (r = 0.33, both P <.01). This
      correlation was not present in healthy control subjects (r = -0.04, P =.9). In
      multivariate and stepwise regression analyses, serum uric acid emerged as the
      strongest predictor of peak leg vascular resistance (standardized coefficient =
      0.61, P <.0001) independent of age, peak VO2, creatinine, New York Heart
      Association class, and diuretic dose. CONCLUSIONS: Hyperuricemia and postischemic
      leg vascular resistance are highest in cachectic patients with CHF, and both are
      directly related independent of diuretic dose and kidney function. The xanthine
      oxidase metabolic pathway may contribute to impaired vasodilator capacity in CHF.

PMID- 11320369
TI  - ADEPT: Addition of the AT1 receptor antagonist eprosartan to ACE inhibitor
      therapy in chronic heart failure trial: hemodynamic and neurohormonal effects.
AB  - BACKGROUND: Persistent activation of the renin-angiotensin-aldosterone-system
      (RAAS) is known to occur in patients with chronic heart failure (CHF) despite
      treatment with angiotensin-converting enzyme inhibitor (ACE) therapy. When added
      to ACE inhibitors, angiotensin II type 1 (AT1) antagonists may allow more
      complete blockade of the RAAS and preserve the beneficial effects of bradykinin
      accumulation not seen with AT1 receptor blockade alone. METHODS: Thirty-six
      patients with stable New York Heart Association class II-IV CHF receiving ACE
      inhibitor therapy were randomly assigned in a double-blind manner to receive
      either eprosartan, a specific competitive AT1 receptor antagonist (400 to 800 mg
      daily, n = 18) or placebo (n = 18) for 8 weeks. The primary outcome measure was
      left ventricular ejection fraction (LVEF) as measured by radionuclide
      ventriculography, and secondary measures were central hemodynamics assessed by
      Swan-Ganz catheterization and neurohormonal effects. RESULTS: There was no change
      in LVEF with eprosartan therapy (mean relative LVEF percentage change [SEM]
      +10.5% [9.3] vs +10.1% [5.0], respectively; difference, 0.4; 95% confidence
      interval [CI], -20.8 to 21.7; P =.97). Eprosartan was associated with a
      significant reduction in diastolic blood pressure and a trend toward a reduction
      in systolic blood pressure compared with placebo (-7.3 mm Hg [95% CI, -14.2 to 
      0.4] diastolic; -8.9 mm Hg [95% CI, -18.6 to 0.8] systolic). No significant
      change in heart rate or central hemodynamics occurred during treatment with
      eprosartan compared with placebo. A trend toward an increase in plasma renin
      activity was noted with eprosartan therapy. Eprosartan was well tolerated, with
      an adverse event profile similar to placebo, whereas kidney function remained
      unchanged. CONCLUSIONS: When added to an ACE inhibitor, eprosartan reduced
      arterial pressure without increasing heart rate. There was no change in LVEF
      after 2 months of therapy with eprosartan.

PMID- 11320370
TI  - Impairment of cardiac autonomic function in patients with Duchenne muscular
      dystrophy: relationship to myocardial and respiratory function.
AB  - BACKGROUND: Previous studies reported an impairment of nervous autonomic activity
      in patients with Duchenne muscular dystrophy (DMD). However, the relationship of
      the autonomic dysfunction to the impairment of cardiac mechanical function and of
      respiratory failure is not completely understood. METHODS: We evaluated cardiac
      autonomic function by time- and frequency-domain heart rate variability (HRV)
      analysis on 24-hour Holter recordings in 60 patients with DMD (16.8 +/- 4.8
      years) and 28 healthy control patients (15.2 +/- 4.6 years, P = not significant).
      The circadian rhythm of R-R interval, low frequency, high frequency, and low
      frequency/high-frequency ratio was also assessed. In all patients, left
      ventricular ejection fraction was measured by 2D echocardiography; respiratory
      function was assessed by spirometry. RESULTS: All HRV parameters were lower in
      patients with DMD than in control subjects, with the percentage of differences
      between adjacent R-R intervals >50 ms (11.6% +/- 8.5% vs 27.3% +/- 14.1%, P
      =.00001) and high frequency (23.9 +/- 10.3 ms vs 36.1 +/- 12.2 ms, P =.0001)
      showing the strongest differences. A significant circadian rhythm of HRV
      variables was present in both groups, but it was considerably flattened in
      patients with DMD. There was no correlation between left ventricular ejection
      fraction and HRV indexes except for a weak correlation with high frequency (r =
      0.30, P =.02) and with low-frequency to high-frequency ratio (r = -0.29, P <.03).
      Similarly modest correlations were found between forced vital capacity and high
      frequency (r = 0.4, P =.007) and low-frequency/high-frequency ratio (r = -0.32, P
      =.026). Multiple regression analysis did not show any independent predictive
      variable for the autonomic impairment. CONCLUSIONS: Our data show a marked
      impairment of cardiac autonomic function in patients with DMD, which appears to
      mainly involve the parasympathetic branch and appears to have a multifactorial
      origin.

PMID- 11320371
TI  - Prevalence of central venous occlusion in patients with chronic defibrillator
      leads.
AB  - BACKGROUND: Many patients with previously implanted ventricular defibrillators
      are candidates for an upgrade to a device capable of atrial-ventricular
      sequential or multisite pacing. The prevalence of venous occlusion after
      placement of transvenous defibrillator leads is unknown. The purpose of this
      study was to determine the prevalence of central venous occlusion in asymptomatic
      patients with chronic transvenous defibrillator leads. METHODS: Thirty
      consecutive patients with a transvenous defibrillator lead underwent bilateral
      contrast venography of the cephalic, axillary, subclavian, and brachiocephalic
      veins as well as the superior vena cava before an elective defibrillator battery
      replacement. The mean time between transvenous defibrillator lead implantation
      and venography was 45 +/- 21 months. Sixteen patients had more than 1 lead in the
      same subclavian vein. No patient had clinical signs of venous occlusion. RESULTS:
      One (3%) patient had a complete occlusion of the subclavian vein, 1 (3%) patient
      had a 90% subclavian vein stenosis, 2 (7%) patients had a 75% to 89% subclavian
      stenosis, 11 (37%) patients had a 50% to 74% subclavian stenosis, and 15 (50%)
      patients had no subclavian stenosis. CONCLUSIONS: The low prevalence of
      subclavian vein occlusion or severe stenosis among defibrillator recipients found
      in this study suggests that the placement of additional transvenous leads in a
      patient who already has a ventricular defibrillator is feasible in a high
      percentage of patients (93%).

PMID- 11320372
TI  - Predictive value of presyncope in patients monitored for assessment of syncope.
AB  - BACKGROUND: The purpose of this study was to assess the diagnostic value of
      recording the cardiac rhythm during presyncope in patients undergoing monitoring
      for undiagnosed syncope. METHODS AND RESULTS: Eighty-five patients (age, 59 +/-
      18 years; 44 men, 41 women) with recurrent unexplained syncope underwent
      prolonged monitoring with an implantable loop recorder. Patients were examined
      for syncope, which was either recurrent or associated with at least 2 presyncopal
      episodes. Patients had a mean of 5.1 +/- 5.5 syncopal episodes in the previous 12
      months, and 70% of patients had symptoms for >2 years. Sixty-two (73%) patients
      had recurrent symptoms during a 12-month follow-up period. Of 150 recurrent
      events captured by the implantable loop recorder, there were 38 (25%) episodes of
      syncope and 112 (75%) episodes of presyncope. Syncope alone recurred in 12
      patients, presyncope in 25, and both in 16. An arrhythmia was present in 64% of
      syncopal events (bradycardia in 16, tachycardia in 2) versus 25% for presyncopal
      events (bradycardia in 7, tachycardia in 3, P =.001). An arrhythmia was detected
      in 9 (56%) of the 16 patients with both syncope and presyncope, which was present
      in all recorded episodes of syncope compared with 6 of 9 presyncopal episodes.
      Patient-related failure to freeze the device after symptoms occurred in 21 (36%)
      of 59 syncopal events compared with 15 (12%) of 127 presyncopal events (P
      =.0001). CONCLUSIONS: Syncope is more likely to be associated with an arrhythmia
      than is presyncope in patients undergoing extended monitoring. Presyncope is a
      nonspecific end point that is frequently associated with sinus rhythm. Patients
      undergoing extended monitoring for syncope should continue to be monitored after
      an episode of presyncope unless an arrhythmia is detected.

PMID- 11320373
TI  - Prognostic value of absolute versus relative measures of the procedural result
      after successful coronary stenting: importance of vessel size in predicting long
      term freedom from target vessel revascularization.
AB  - BACKGROUND: The procedural result is a major determinant of the incidence of 6
      month target vessel revascularization (TVR) after successful coronary stenting.
      However, the prognostic implications of the different measures of the procedural
      result or procedural end points have not been directly compared. In this study,
      we sought to assess and compare the impact of achieving different procedural end
      points on the long-term (2-year) incidence of TVR. METHODS AND RESULTS: We
      studied 234 patients in whom 1 or 2 stents were successfully deployed and
      ultrasound imaging performed after angiographic optimization. End points included
      a visually estimated angiographic residual stenosis <10% and ultrasound stent-to
      mean reference lumen area > or = 80%. After 2 years, TVR was required in 48
      (20.5%) patients. Qualitative predictors of TVR were vein graft lesions, 3-vessel
      disease, and baseline TIMI flow grade < 3. Quantitatively, reference diameter by
      quantitative coronary angiography (QCA), final minimum lumen diameter (MLD) by
      QCA, and in-stent minimum lumen area (MLA) by ultrasound were predictive of TVR.
      Stent-to-reference ratios were not significantly predictive of TVR. By
      multivariable analysis, vein graft location and MLA by ultrasound were the only
      significant predictors of TVR (relative risk, 2.9 [1.5, 5.4] and 0.72 [0.6, 0.9],
      respectively). Receiver operator curves for MLD by QCA and MLA by ultrasound were
      similar in predicting TVR. Neither was significantly superior to reference vessel
      diameter. CONCLUSIONS: Commonly used angiographic and ultrasound stent-to
      reference ratios do not predict the incidence of TVR. Absolute measures of the
      lumen size (MLA by ultrasound and MLD by QCA) were the most important
      quantitative predictors of TVR within 2 years. This emphasizes the role of the
      vessel size as the limiting factor in determining the long-term outcome of
      coronary stenting.

PMID- 11320375
TI  - Use of routine functional testing after percutaneous transluminal coronary
      angioplasty: results from the ROSETTA Registry.
AB  - BACKGROUND: The American College of Cardiology (ACC)/American Heart Association
      (AHA) guidelines for exercise testing suggest that only selected groups of high
      risk patients should undergo routine functional testing after percutaneous
      transluminal coronary angioplasty (PTCA) for the detection of restenosis.
      OBJECTIVES: Our purpose was (1) to document the patterns of use of post-PTCA
      functional testing and (2) to determine whether the choice of functional testing
      strategy is related to clinical characteristics of patients or whether physicians
      use a similar strategy for all their patients. METHODS: The Routine Versus
      Selective Exercise Treadmill Testing After Angioplasty (ROSETTA) Registry is a
      prospective study examining the use of functional testing among 788 patients at
      13 centers in 5 countries. RESULTS: During the 6-month period after a successful
      PTCA, 49% of patients underwent functional testing (range among centers 10%-81%).
      Among patients who underwent functional testing, 39% had a clinical indication
      and 61% had functional testing as a routine follow-up. The first functional test
      was performed a median of 7 weeks after PTCA, with 13% of patients having second
      tests at a median of 14 weeks and 4% having additional tests at a median of 20
      weeks. Univariate and multivariate analyses demonstrated that the chief
      determinant of the use of routine functional testing was clinical center. Aside
      from age (P <.0001), no baseline clinical or procedural characteristics were
      consistently associated with the use of routine functional testing after PTCA.
      CONCLUSIONS: Physicians do not appear to be adhering to the ACC/AHA guidelines
      for exercise testing regarding the routine use of post-PTCA functional testing.
      None of the clinical characteristics identified by the ACC/AHA guidelines were
      associated with the routine use of post-PTCA functional testing, and the primary
      determinant of functional testing was the location of the center at which the
      patient had the PTCA.

PMID- 11320374
TI  - Six-month angiographic follow-up after intravascular ultrasound-guided stenting
      of infarct-related artery: comparison with non-infarct-related artery.
AB  - BACKGROUND: Compared with balloon angioplasty, stenting has been established as
      an effective treatment modality to reduce restenosis in patients with acute
      myocardial infarction. However, the immediate results that predict favorable long
      term outcomes in the acute infarct stenting are unknown. Therefore, we evaluated
      long-term outcomes of stenting for infarct-related artery (IRA) lesions by using
      intravascular ultrasound (IVUS) compared with that of stenting for non-IRA
      lesions. METHODS: IVUS-guided coronary stenting was successfully performed in 510
      native coronary lesions (105 IRA vs 405 non-IRA). A 6-month follow-up angiogram
      was performed in 419 (82.2%) lesions: 87 (82.9%) IRA lesions and 332 (82.0%) non
      IRA lesions. Coronary stenting on the IRA lesions was successfully performed
      within 7 to 10 days after onset of infarction in 42 patients and within 12 hours
      in 45 patients. Results were evaluated by clinical, angiographic, and IVUS
      methods. RESULTS: There were no significant differences in clinical and
      angiographic variables between the two groups. IVUS variables including reference
      vessel area and minimal stent area were also similar between the two groups.
      There was no significant difference in angiographic restenosis rate between the
      two groups in cases of minimal stent area > or = 7 mm(2): 12.8% (6 of 47) in IRA
      versus 19.1% (33 of 173) in non-IRA lesions (P = .315). However, the angiographic
      restenosis rate in cases of minimal stent area <7 mm(2) was 50% (20 of 40) in IRA
      lesions versus 31.5% (50 of 159) in non-IRA lesions (P = .028). CONCLUSIONS:
      Angiographic restenosis is significantly higher in stenting for IRA lesions
      compared with that for non-IRA lesions in cases of minimal stent area < 7 mm(2).

PMID- 11320376
TI  - Antithrombotic therapy after prosthetic cardiac valve implantation: improving
      postoperative, long-term patient management. Introduction.

PMID- 11320377
TI  - Evolution of prosthetic heart valves.

PMID- 11320378
TI  - The "ideal" replacement heart valve.

PMID- 11320379
TI  - Designing trials for testing prosthetic cardiac valves: a Food and Drug
      Administration perspective.

PMID- 11320380
TI  - International differences in cardiovascular clinical trials. Introduction.

PMID- 11320381
TI  - International differences in cardiovascular clinical trials.

PMID- 11320382
TI  - International differences in treatment effects in cardiovascular clinical trials.

PMID- 11320383
TI  - Single-day loading dose of oral amiodarone for the prevention of new-onset atrial
      fibrillation after coronary artery bypass surgery.
AB  - BACKGROUND: Various regimens have been proposed for the prevention of
      postoperative atrial fibrillation, including the use of intravenous and oral
      amiodarone. The purpose of this study was to determine the effectiveness of a
      single-day loading dose of oral amiodarone in prophylaxis of atrial fibrillation
      during the 7 days after coronary artery bypass surgery. METHODS: We conducted a
      double-blind, randomized, placebo-controlled study encompassing 315 consecutive
      patients who underwent coronary artery bypass surgery. They received either
      amiodarone (159 patients) or placebo (156 patients). Therapy consisted of a
      single oral loading dose of 1200 mg of amiodarone 1 day before surgery, followed
      by the maintenance dose of 200 mg daily during the next 7 days. Only episodes of
      atrial fibrillation lasting more than 1 hour or associated with hemodynamic
      compromise were taken into consideration. RESULTS: Overall, the incidence of
      atrial fibrillation was similar in patients who received amiodarone (31/159,
      19.5%) and placebo (33/156, 21.2%) (P = .78). However, amiodarone reduced the
      incidence of atrial fibrillation in elderly patients (age > or = 60 years): it
      occurred in 20 of 75 (26.7%) patients on amiodarone and in 28 of 65 (43.1%)
      patients in the placebo group (P = .05). There were no differences between the
      study groups regarding the postoperative intrahospital morbidity and mortality
      and the duration of hospital stay. CONCLUSIONS: A single-day loading dose of oral
      amiodarone (1200 mg) does not prevent postoperative atrial fibrillation in a
      general population of patients undergoing coronary artery bypass surgery.
      However, it appears that this regimen reduces the occurrence of postoperative
      atrial fibrillation in elderly patients.

PMID- 11320384
TI  - Acute effects of melatonin administration on cardiovascular autonomic regulation
      in healthy men.
AB  - BACKGROUND: Previous studies have suggested that melatonin, a major pineal
      hormone, possibly modulates the autonomic nervous system in animals. The aim of
      this study was to examine the effects of melatonin administration on heart rate
      variability (HRV) in human beings. METHODS: In 26 healthy men, melatonin (2 mg)
      or placebo was randomly administered. Power spectral analysis of HRV and blood
      pressure monitoring were performed in the supine position before and 60 minutes
      after administration and in the standing position 60 minutes after
      administration. Plasma catecholamine levels were also assessed. RESULTS: No
      differences in any baseline parameters were found between the two groups.
      Compared with placebo, melatonin administration within 60 minutes increased R-R
      interval, the square root of the mean of the squared differences between adjacent
      normal R-R intervals, high-frequency power, and low-frequency power of HRV and
      decreased the low-frequency to high-frequency ratio and blood pressure in the
      supine position (all P <.01). Plasma norepinephrine and dopamine levels in the
      supine position 60 minutes after melatonin administration were lower compared
      with placebo (P <.05 and P <.01, respectively). Standing up resulted in the
      decrease of HRV and the increase of blood pressure and plasma catecholamine
      levels in both administration groups, and the differences between the groups
      found in the supine position disappeared. CONCLUSIONS: These findings indicate
      that melatonin administration increased cardiac vagal tone in the supine position
      in awake men. Melatonin administration also may exert suppressive effects on
      sympathetic tone.

PMID- 11320385
TI  - The efficacy of a Salmonella typhi Vi conjugate vaccine in two-to-five-year-old
      children.
AB  - BACKGROUND: Typhoid fever is common in developing countries. The licensed typhoid
      vaccines confer only about 70 percent immunity, do not protect young children,
      and are not used for routine vaccination. A newly devised conjugate of the
      capsular polysaccharide of Salmonella typhi, Vi, bound to nontoxic recombinant
      Pseudomonas aeruginosa exotoxin A (rEPA), has enhanced immunogenicity in adults
      and in children 5 to 14 years old and has elicited a booster response in children
      2 to 4 years old. METHODS: In a double-blind, randomized trial, we evaluated the
      safety, immunogenicity, and efficacy of the Vi-rEPA vaccine in children two to
      five years old in 16 communes in Dong Thap Province, Vietnam. Each of the 11,091
      children received two injections six weeks apart of either Vi-rEPA or a saline
      placebo. Cases of typhoid, diagnosed by the isolation of S. typhi from blood
      cultures after 3 or more days of fever (a temperature of 37.5 degrees C or
      higher), were identified by active surveillance over a period of 27 months. We
      estimated efficacy by comparing the attack rate of typhoid in the vaccine group
      with that in the placebo group. RESULTS: S. typhi was isolated from 4 of the 5525
      children who were fully vaccinated with Vi-rEPA and from 47 of the 5566 children
      who received both injections of placebo (efficacy, 91.5 percent; 95 percent
      confidence interval, 77.1 to 96.6; P<0.001). Among the 771 children who received
      only one injection, there was 1 case of typhoid in the vaccine group and 8 cases
      in the placebo group. Cases were distributed evenly among all age groups and
      throughout the study period. No serious adverse reactions were observed. In all
      36 children studied four weeks after the second injection of the vaccine, levels
      of serum IgG Vi antibodies had increased by a factor of 10 or more. CONCLUSIONS:
      The Vi-rEPA conjugate typhoid vaccine is safe and immunogenic and has more than
      90 percent efficacy in children two to five years old. The antibody responses and
      the efficacy suggest that this vaccine should be at least as protective in
      persons who are more than five years old.

PMID- 11320386
TI  - DNA content as a prognostic marker in patients with oral leukoplakia.
AB  - BACKGROUND: Oral leukoplakia may develop into squamous-cell carcinoma, which has
      a poor prognosis. Risk factors for oral carcinoma have been identified, but there
      are no reliable predictors of the outcome in individual patients with oral
      leukoplakia. METHODS: We identified 150 patients with oral leukoplakia that was
      classified as epithelial dysplasia and measured the nuclear DNA content (ploidy)
      of the lesions to determine whether DNA ploidy could be used to predict the
      clinical outcome. Biopsy specimens obtained at annual follow-up visits were
      graded histologically and classified with respect to DNA content in a blinded
      fashion. Disease-free survival was assessed in relation to DNA ploidy and the
      histologic grade. The mean duration of follow-up was 103 months (range, 4 to
      165). RESULTS: Among 150 patients with verified epithelial dysplasia, a carcinoma
      developed in 36 (24 percent). Of the 150 patients, 105 (70 percent) had diploid
      (normal) lesions, 20 (13 percent) had tetraploid (intermediate) lesions, and 25
      (17 percent) had aneuploid (abnormal) lesions at the time of the initial
      diagnosis. A carcinoma developed in 3 of the 105 patients with diploid lesions (3
      percent), as compared with 21 of the 25 patients with aneuploid lesions (84
      percent), yielding a negative predictive value of 97 percent with respect to the
      diploid lesions and a positive predictive value of 84 percent with respect to the
      aneuploid lesions. Carcinoma developed in 12 of 20 patients with tetraploid
      lesions (60 percent). The mean time from the initial assessment of the DNA
      content to the development of a carcinoma was 35 months (range, 4 to 57) in the
      group with aneuploid lesions and 49 months (range, 8 to 78) in the group with
      tetraploid lesions (P=0.02). The cumulative disease-free survival rate was 97
      percent among the group with diploid lesions, 40 percent among the group with
      tetraploid lesions, and 16 percent among the group with aneuploid lesions
      (P<0.001). CONCLUSIONS: The DNA content in cells of oral leukoplakia can be used
      to predict the risk of oral carcinoma.

PMID- 11320387
TI  - Temporal aspects of heparin-induced thrombocytopenia.
AB  - BACKGROUND: Heparin-induced thrombocytopenia is a relatively common antibody
      mediated drug reaction. We studied the temporal relation between previous or
      current heparin therapy and the onset of heparin-induced thrombocytopenia.
      METHODS: We examined the time between the start of heparin therapy and the onset
      of thrombocytopenia in 243 patients with serologically confirmed heparin-induced
      thrombocytopenia. We also investigated the persistence of circulating heparin
      dependent antibodies by performing a platelet serotonin-release assay and an
      assay for antibodies against platelet factor 4. The outcome in seven patients who
      had previously had an episode of heparin-induced thrombocytopenia and were later
      treated again with heparin was also examined. RESULTS: A fall in the platelet
      count beginning four or more days after the start of heparin therapy occurred in
      170 of the 243 patients (70 percent); in these patients, a history of previous
      heparin treatment did not influence the timing of the onset of thrombocytopenia.
      In the remaining 73 patients (30 percent), the onset of thrombocytopenia was
      rapid (median time of onset, 10.5 hours after the start of heparin
      administration); all these patients had been treated with heparin within the
      previous 100 days. During recovery from thrombocytopenia, heparin-dependent
      antibodies in the serum fell to undetectable levels at a median of 50 to 85 days,
      depending on the assay performed. In the seven patients who were given heparin
      again after the disappearance of heparin-dependent antibodies, a new episode of
      heparin-induced thrombocytopenia did not occur. CONCLUSIONS: Heparin-induced
      thrombocytopenia can begin rapidly in patients who have received heparin within
      the previous 100 days. Heparin-dependent antibodies do not invariably reappear
      with subsequent heparin use.

PMID- 11320388
TI  - Images in clinical medicine. Leprosy.

PMID- 11320389
TI  - Global trends in resistance to antituberculosis drugs. World Health Organization
      International Union against Tuberculosis and Lung Disease Working Group on Anti
      Tuberculosis Drug Resistance Surveillance.
AB  - BACKGROUND: Data on global trends in resistance to antituberculosis drugs are
      lacking. METHODS: We expanded the survey conducted by the World Health
      Organization and the International Union against Tuberculosis and Lung Disease to
      assess trends in resistance to antituberculosis drugs in countries on six
      continents. We obtained data using standard protocols from ongoing surveillance
      or from surveys of representative samples of all patients with tuberculosis. The
      standard sampling techniques distinguished between new and previously treated
      patients, and laboratory performance was checked by means of an international
      program of quality assurance. RESULTS: Between 1996 and 1999, patients in 58
      geographic sites were surveyed; 28 sites provided data for at least two years.
      For patients with newly diagnosed tuberculosis, the frequency of resistance to at
      least one antituberculosis drug ranged from 1.7 percent in Uruguay to 36.9
      percent in Estonia (median, 10.7 percent). The prevalence increased in Estonia,
      from 28.2 percent in 1994 to 36.9 percent in 1998 (P=0.01), and in Denmark, from
      9.9 percent in 1995 to 13.1 percent in 1998 (P=0.04). The median prevalence of
      multidrug resistance among new cases of tuberculosis was only 1.0 percent, but
      the prevalence was much higherin Estonia (14.1 percent), Henan Province in China
      (10.8 percent), Latvia (9.0 percent), the Russian oblasts of Ivanovo (9.0
      percent) and Tomsk (6.5 percent), Iran (5.0 percent), and Zhejiang Province in
      China (4.5 percent). There were significant decreases in multidrug resistance in
      France and the United States. In Estonia, the prevalence in all cases increased
      from 11.7 percent in 1994 to 18.1 percent in 1998 (P<0.001). CONCLUSIONS:
      Multidrug-resistant tuberculosis continues to be a serious problem, particularly
      among some countries of eastern Europe. Our survey also identified areas with a
      high prevalence of multidrug-resistant tuberculosis in such countries as China
      and Iran.

PMID- 11320390
TI  - Cardiac resuscitation.

PMID- 11320391
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 13-2001. A 19-year-old man with bouts of hypertension and severe
      headaches.

PMID- 11320392
TI  - Polysaccharide conjugate typhoid vaccine.

PMID- 11320393
TI  - Molecular markers of the risk of oral cancer.

PMID- 11320394
TI  - Drug treatment of anxiety disorders in children.

PMID- 11320395
TI  - Do we need guidelines or 'songlines'?

PMID- 11320396
TI  - How can we translate advances in respiratory diseases into improved care?

PMID- 11320397
TI  - Re: Physician asthma management practices in Canada.

PMID- 11320399
TI  - Alpha1-antitrypsin deficiency: a position statement of the Canadian Thoracic
      Society.
AB  - OBJECTIVE: To prepare new guidelines for the Canadian Thoracic Society (CTS)
      regarding severe alpha1-antitrypsin (AAT) deficiency and AAT replacement therapy.
      MATERIALS AND METHODS: Previously published guidelines and the medical literature
      about AAT deficiency and AAT replacement were reviewed. The prepared statement
      was reviewed and approved by the CTS Standards and Executive Committees. RESULTS:
      Three studies evaluated AAT replacement. The National Heart, Lung and Blood
      Institute's AAT Registry was a nonrandomized comparison of patients receiving and
      not receiving AAT replacement, and evaluated the decline in forced expiratory
      volume in 1 s (FEV1) in 927 subjects. The rate of FEV1 decline was significantly
      less in those receiving AAT treatment (66 +/- SE 5 mL/year versus 93 +/- SE 11
      mL/year; P=0.03) only in the subgroup with FEV1 35% to 49% predicted. In another
      study comparing 198 German patients receiving weekly AAT infusions and 97
      untreated Danish patients, the mean annual decline in FEV1 was significantly less
      in treated patients only in the subgroup with FEV1 31% to 65% predicted (62 mL
      versus 83 mL, P=0.04). Neither of these studies was a randomized, controlled
      study and, thus, cannot be taken as proof of efficacy. A randomized, double
      blind, placebo controlled trial of monthly replacement therapy over three years
      in 56 exsmokers with severe AAT deficiency and moderate emphysema showed a trend
      (P=0.07) favouring slower progression of emphysema by computed tomography scan in
      the group receiving AAT replacement. CONCLUSIONS: AAT replacement therapy has not
      been proven definitively to be clinically effective in reducing the progression
      of disease in AAT-deficient patients, but there is a possible benefit to selected
      patients. A placebo controlled, randomized clinical trial of AAT replacement
      therapy is required. The authors recommend reserving AAT replacement therapy for
      AAT-deficient patients with impaired FEV1 of 35% to 50% predicted who have quit
      smoking and are on optimal medical therapy but continue to show a rapid decline
      in FEV1, and participation of all AAT-deficient subjects in the Canadian AAT
      Registry.

PMID- 11320400
TI  - Etiology of exudative pleural effusions in adults in North Lebanon.
AB  - OBJECTIVE: To establish the clinical pattern and etiology of exudative pleural
      effusions in adults in North Lebanon. MATERIALS AND METHODS: All patients aged 21
      years and older who were admitted with exudative pleural effusions to the
      Husseini Hospital, Tripoli, North Lebanon, between 1997 and 1999 were studied
      prospectively. RESULTS: Of 165 patients with exudative pleural effusions, 114
      (69.1%) were men and 51 (30.9%) were women. The most frequent cause of exudative
      pleural effusions was tuberculosis (43.7%), followed by malignancy (32.1%). The
      majority (88.7%) of malignant pleural effusions were due to lung cancer.
      Tuberculous effusions were more frequent in the first five decades of life
      (66.7%) and were the most common type of pleural effusion, accounting for 68.6%
      of patients younger than 50 years of age. Malignant effusions were more frequent
      among the older age groups, with 73.6% of patients with malignant effusions being
      older than 50 years of age. Most types of exudative pleural effusions showed a
      preference for the right side of the thorax. Of the diagnostic procedures used in
      the present study, the most useful were histological examination and culture of
      pleural biopsies. CONCLUSIONS: In North Lebanon, the clinical pattern and
      etiology of exudative pleural effusions are similar to those in the developing
      countries; the most frequent cause of pleural exudates is tuberculosis, followed
      by malignancy, particularly malignancy due to lung cancer.

PMID- 11320401
TI  - Hypersensitivity pneumonitis with normal high resolution computed tomography
      scans.
AB  - A case of symptomatic hypersensitivity pneumonitis with normal high resolution
      computed tomography (CT) scans is presented. The patient, a 32-year-old man with
      systemic lupus erythematosus, had a chronic, progressive history of respiratory
      symptoms, abnormal findings on examination and abnormal pulmonary function tests
      but normal high resolution CT scans of the chest. Diagnosis was made through open
      lung biopsy. Clinical improvement was seen on removal of the offending antigen.
      The literature on the utility of high resolution CT scans in hypersensitivity
      pneumonitis is reviewed.

PMID- 11320402
TI  - Orthodeoxia and platypnea secondary to a patent foramen ovale despite normal
      right-sided cardiac pressures.
AB  - Numerous cases of orthodeoxia and platypnea have been reported. Some have been
      found to be due to intracardiac shunts despite normal intracardiac pressures. In
      the case presented, a 79-year-old woman was noted to have orthodeoxia and
      platypnea secondary to a patent foramen ovale (PFO) despite normal intracardiac
      pressures. She recovered after closure of the PFO. The authors postulate that
      recent vertebral fractures and subsequent kyphosis, as well as a dilated thoracic
      aorta, altered intrathoracic relationships and may have led to a stream of venous
      return being directed across the PFO in the upright position, despite normal
      intracardiac pressures.

PMID- 11320403
TI  - Gene therapy effectiveness differs for neuronal survival and behavioral
      performance.
AB  - If neuronal gene therapy is to be clinically useful, it is necessary to
      demonstrate neuroprotection when the gene is introduced after insult. We now
      report equivalent neuronal protection if calbindin D(28K) gene transfer via
      herpes simplex virus amplicon vector occurs immediately, 30 min, or 1 h after an
      excitotoxic insult, but not after a 4 h delay. Behavioral performance was
      evaluated for immediate and 1 h delay groups using a hippocampal-dependent task.
      Despite equivalent magnitude and pattern of sparing of neurons with the immediate
      and 1 h delay approaches, the delay animals took a significantly longer time
      after insult to return to normal performance.

PMID- 11320404
TI  - Single chain Fv: a ligand in receptor-mediated gene delivery.
AB  - We have used an anti-human polymeric immunoglobulin receptor (pIgR) single chain
      Fv (scFv) to deliver reporter genes to epithelial cells in vitro. The scFv was
      constructed from a monoclonal antibody directed against pIgR and a cysteine
      residue was added at the carboxyl end to facilitate its conjugation to polylysine
      (polyK) via the heterobifunctional cross-linker SPDP. ScFv-cys was expressed in
      Drosophila S2 cells and purified to homogeneity using conventional column
      chromatography. ScFv-polyK, and polyK as control, were condensed with a DNA
      expression plasmid containing the luciferase reporter gene driven by the CMV
      promoter into unimolecular (with respect to DNA) complexes under high salt
      conditions. Target cells were MDCK cells transfected with human pIgR and
      repeatedly sorted for high-level receptor expression, with untransfected MDCK
      cells as control. Receptor-bearing MDCK cells were readily transfected by scFv
      cys containing, pIgR directed complexes, and expression could be blocked by
      addition of excess human secretory component (SC), the extracellular portion of
      pIgR. In contrast, MDCK cells that did not express pIgR were not transfected.
      Nontargeted complexes were not effective in transfecting MDCK cells with or
      without pIgR. Targeted complexes also transfected human tracheal epithelial cells
      in primary culture, corroborating the pIgR-mediated gene delivery. These data
      indicate that a scFv directed against human pIgR can direct foreign genes
      specifically into receptor-bearing cells in vitro. We have expressed and purified
      a ligand that is efficient and specific in pIgR-mediated gene delivery.

PMID- 11320405
TI  - Envelope fusion protein binding studies in an inducible model of retrovirus
      receptor expression and in CD34(+) cells emphasize limited transduction at low
      receptor levels.
AB  - Successful gene therapy for the treatment of heritable or acquired diseases
      typically requires high efficiency gene transfer and sustained transgene
      expression. Indirect evidence on the basis of RNA analysis and in vivo
      competitive repopulation experiments in animal models suggests a correlation
      between transduction efficiency and the abundance of retrovirus receptors on the
      hematopoietic target cell. However, transduction by oncoretroviral vectors is
      also subject to other factors such as target cell cycle status and the
      composition of the virus-containing medium, making it difficult to determine the
      level of receptor expression required for efficient transduction. In the present
      study we investigated the impact of receptor expression level on transduction by
      a vector with a gibbon ape leukemia virus (GALV) envelope protein in a
      tetracycline-inducible tissue culture model that allowed for the cell cycle
      independent, regulated expression of the GALV receptor (Pit1) in otherwise non
      susceptible NIH 3T3 cells. Up-regulation of receptor RNA expression by 4.5-fold
      resulted in a mean 150-fold increase in transduction efficiency. We then analyzed
      cell surface expression of the Pit1 receptor using a fusion protein consisting of
      GALV SU portion of the viral envelope protein linked to the human IgG Fc. These
      experiments showed that tetracycline-regulated receptor induction resulted in a
      dose-dependent increase in binding of fusion protein. At maximum induction fusion
      protein binding increased up to five-fold which paralleled the increase in RNA
      expression, and correlated with the improved transduction efficiency. Finally,
      studies of pseudotype-specific fusion protein binding to human CD34-enriched
      cells revealed increased expression of retrovirus receptors after cytokine
      stimulation, although overall receptor expression in CD34(+)cells remained lower
      than in fibroblast cell lines efficiently transduced by amphotropic and GALV
      vectors.

PMID- 11320406
TI  - Efficient in vitro and in vivo gene regulation of a retrovirally delivered pro
      apoptotic factor under the control of the Drosophila HSP70 promoter.
AB  - We have developed a self-inactivating retroviral vector system with an internal,
      inducible Drosophila HSP70 promoter. This vector system delivers the desired
      transgene into cells rapidly and efficiently. It generates mixed populations of
      transduced cells where the transgene is inducible, and does not require the
      isolation of specific clones. Since the transgene is not expressed (or poorly
      expressed) at the restrictive condition (34 degrees C), mixed populations can be
      selected in which tumor suppressors or other inhibitory genes can be strongly
      induced upon changing the conditions (39 degrees C or the plant amino acid L
      canavanine). This retroviral vector should be very useful for the expression of
      sequences that are poorly tolerated by cells, and is also active in animals.

PMID- 11320407
TI  - Direct transfection and activation of human cutaneous dendritic cells.
AB  - Gene therapy techniques can be important tools for the induction and control of
      immune responses. Antigen delivery is a critical challenge in vaccine design, and
      DNA-based immunization offers an attractive method to deliver encoded transgenic
      protein antigens. In the present study, we used a gene gun to transfect human
      skin organ cultures with a particular goal of expressing transgenic antigens in
      resident cutaneous dendritic cells. Our studies demonstrate that when delivered
      to human skin, gold particles are observed primarily in the epidermis, even when
      high helium delivery pressures are used. We demonstrate that Langerhans cells
      resident in the basal epidermis can be transfected, and that biolistic gene
      delivery is sufficient to stimulate the activation and migration of skin
      dendritic cells. RT-PCR analysis of dendritic cells, which have migrated from
      transfected skin, demonstrates the presence of transgenic mRNA, indicating direct
      transfection of cutaneous dendritic cells. Importantly, transfected epidermal
      Langerhans cells can efficiently present a peptide derived from the transgenic
      melanoma antigen MART-1 to a MART-1-specific CTL. Taken together, our results
      demonstrate direct transfection, activation, and antigen-specific stimulatory
      function of in situ transduced human Langerhans cells.

PMID- 11320408
TI  - Successful therapeutic effect in a mouse model of erythropoietic protoporphyria
      by partial genetic correction and fluorescence-based selection of hematopoietic
      cells.
AB  - Erythropoietic protoporphyria is characterized clinically by skin
      photosensitivity and biochemically by a ferrochelatase deficiency resulting in an
      excessive accumulation of photoreactive protoporphyrin in erythrocytes, plasma
      and other organs. The availability of the Fech(m1Pas)/Fech(m1Pas) murine model
      allowed us to test a gene therapy protocol to correct the porphyric phenotype.
      Gene therapy was performed by ex vivo transfer of human ferrochelatase cDNA with
      a retroviral vector to deficient hematopoietic cells, followed by re-injection of
      the transduced cells with or without selection in the porphyric mouse.
      Genetically corrected cells were separated by FACS from deficient ones by the
      absence of fluorescence when illuminated under ultraviolet light. Five months
      after transplantation, the number of fluorescent erythrocytes decreased from 61%
      (EPP mice) to 19% for EPP mice engrafted with low fluorescent selected BM cells.
      Absence of skin photosensitivity was observed in mice with less than 20% of
      fluorescent RBC. A partial phenotypic correction was found for animals with 20 to
      40% of fluorescent RBC. In conclusion, a partial correction of bone marrow cells
      is sufficient to reverse the porphyric phenotype and restore normal
      hematopoiesis. This selection system represents a rapid and efficient procedure
      and an excellent alternative to the use of potentially harmful gene markers in
      retroviral vectors.

PMID- 11320409
TI  - The role of receptors in the maturation-dependent adenoviral transduction of
      myofibers.
AB  - One of the major hurdles facing the application of adenoviral gene transfer to
      skeletal muscle is the maturation-dependent transduction of muscle myofibers. It
      was recently proposed that the viral receptors (Coxsackie and adenovirus receptor
      (CAR) and the integrins alphavbeta3/beta5) play a major role in the poor
      adenoviral transduction of mature myofibers. Here we report the findings of
      morphological studies designed to determine experimentally the role of receptors
      in the adenoviral transduction of mature myofibers. First, we observed that the
      expression of both attachment and internalization receptors did not change
      significantly during muscle development. Second, when an extended tropism
      adenoviral vector (AdPK) that attaches to heparan sulfate proteoglycan (HSP) is
      used, a significant reduction of adenoviral transduction still occurs in mature
      myofibers despite HSP's high expression in mature skeletal muscle fibers. Third,
      when the adeno-associated virus (AAV) is used, which also utilizes HSP as a viral
      receptor, muscle fibers at different maturities can be highly transduced. Fourth,
      the pre-irradiation of the skeletal muscle of newborn mice to inactivate
      myoblasts dramatically decreased the transduction level of Ad and AdPK, but had
      no effect on AAV-mediated viral transduction of immature myofibers. These results
      taken together suggest that the viral receptor(s) is not a major determinant in
      maturation-dependent adenoviral transduction of myofibers.

PMID- 11320410
TI  - Gene transfer of antisense hypoxia inducible factor-1 alpha enhances the
      therapeutic efficacy of cancer immunotherapy.
AB  - Solid tumors meet their demands for nascent blood vessels and increased
      glycolysis, to combat hypoxia, by activating multiple genes involved in
      angiogenesis and glucose metabolism. Hypoxia inducible factor-1 (HIF-1) is a
      constitutively expressed basic helix-loop-helix transcription factor, formed by
      the assembly of HIF-1alpha and HIF-1beta (Arnt), that is stablized in response to
      hypoxia, and rapidly degraded under normoxic conditions. It activates the
      transcription of genes important for maintaining oxygen homeostasis. Here, we
      demonstrate that engineered down-regulation of HIF-1alpha by intratumoral gene
      transfer of an antisense HIF-1alpha plasmid leads to the down-regulation of VEGF,
      and decreased tumor microvessel density. Antisense HIF-1alpha monotherapy
      resulted in the complete and permanent rejection of small (0.1 cm in diameter) EL
      4 tumors, which is unusual for an anti-angiogenic agent where transient
      suppression of tumor growth is the norm. It induced NK cell-dependent rejection
      of tumors, but failed to stimulate systemic T cell-mediated anti-tumor immunity,
      and synergized with B7-1-mediated immunotherapy to cause the NK cell and CD8 T
      cell-dependent rejection of larger EL-4 tumors (0.4 cm in diameter) that were
      refractory to monotherapies. Mice cured of their tumors by combination therapy
      resisted a rechallenge with parental tumor cells, indicating systemic antitumor
      immunity had been achieved. In summary, whilst intensive investigations are in
      progress to target the many HIF-1 effectors, the results herein indicate that
      blocking hypoxia-inducible pathways and enhancing NK-mediated antitumor immunity
      by targeting HIF-1 itself may be advantageous, especially when combined with
      cancer immunotherapy.

PMID- 11320411
TI  - Recombinant angiostatin prevents retinal neovascularization in a murine
      proliferative retinopathy model.
AB  - Retinal neovascularization is central to the pathogenesis of proliferative
      diabetic retinopathy, the leading cause of blindness among the middle-aged
      population. Angiostatin, a proteolytic fragment of plasminogen is one of the most
      promising inhibitors of angiogenesis currently in clinical trials. Here we show
      that recombinant angiostatin can inhibit retinal neovascularization in a mouse
      model of proliferative retinopathy. Because proliferative diabetic retinopathy is
      a recurrent disease, effective therapy will need to be sustained. Recombinant
      adeno-associated viruses permit long-term expression of transfected genes;
      however, they can only accommodate a small insert sequence. Thus, we engineered
      and tested a shortened recombinant angiostatin derivative containing a signal
      sequence to permit secretion. Recombinant protein was purified from the medium of
      transfected HEK293 cells and injected subcutaneously into treated animals. The
      retinal vasculature was analyzed in retinal flat mounts and using
      immunohistochemically stained sections. Both methods demonstrate that this short,
      secreted form of angiostatin is effective in reducing the development of blood
      vessels in a nontumor environment and has therapeutic potential for neovascular
      retinopathies such as diabetic retinopathy, retinopathy of prematurity, retinal
      vein occlusion and, possibly, age-related macular degeneration.

PMID- 11320412
TI  - Interruption of coding sequences by heterologous introns can enhance the
      functional expression of recombinant genes.
AB  - Sustained expression of recombinant proteins is a critical factor for the
      effectiveness of numerous applications in the biomedical sciences including the
      treatment of human disease by gene therapy, the large scale production of
      therapeutic proteins, as well as the investigation of gene function by
      transgenesis or cell type specific mutagenesis. Although much attention has been
      paid to the optimisation of regulatory sequences such as promoters, untranslated
      regions and polyadenylation signals, effective and sustained expression of
      recombinant genes in vivo is often difficult to achieve. Here we report that the
      creation of artificial exons, by insertion of two short heterologous introns into
      open reading frames, is not only compatible with functional expression, but also
      leads to a 30-fold enhancement of mRNA production for both green fluorescent
      protein and the bacteriophage P1-derived Cre recombinase. The levels of green
      fluorescence were increased five-fold in cell lines and sustained long-term
      expression at increased levels was observed in rat brain after transduction with
      a herpes simplex virus-based vector. The data presented identify a means by which
      the expression of recombinant genes can be enhanced considerably, in addition to
      and independently from the surrounding regulatory sequences. The method should
      help obtain sustained and effective expression of recombinant proteins in vivo.

PMID- 11320414
TI  - Human pathogens associated with raw produce and unpasteurized juices, and
      difficulties in decontamination.
AB  - The ability of public health agencies to identify, through enhanced epidemiologic
      and surveillance techniques, raw fruits, vegetables, and unpasteurized juices as
      probable sources of infectious microorganisms, has undoubtedly resulted in
      increased numbers of documented outbreaks. Changes in agronomic, harvesting,
      distribution, processing, and consumption patterns and practices have also likely
      contributed to this increase. The risk of illness associated with raw produce and
      unpasteurized produce products can be reduced by controlling or preventing
      contamination, or by removing or killing pathogenic microorganisms by washing or
      treating them with sanitizers. However, the hydrophobic cutin, diverse surface
      morphologies, and abrasions in the epidermis of fruits and vegetables limit the
      efficacy of these treatments.

PMID- 11320413
TI  - Treatment of bladder cancer cells in vitro and in vivo with 2-5A antisense
      telomerase RNA.
AB  - Bladder cancer is the most common malignant tumor of the urinary tract. Novel
      treatment approaches are essential because of the failure of current treatment
      options to cure a high percentage of patients. Telomerase, a ribonucleoprotein,
      is detected in almost all bladder cancer, but not in normal bladder tissues.
      Therefore, telomerase is expected to be a very promising candidate for targeted
      therapy of bladder cancer. In this study, we synthesized a 19-mer antisense
      oligonucleotide against the RNA component of human telomerase (hTR) linked to a 2
      5A molecule (2-5A-anti-hTR) and investigated its antitumor effect against bladder
      cancer cells. The 2-5A antisense strategy relies on the recruitment and
      activation of RNase L at the site of targeted RNA sequence. Here we demonstrate
      that treatment with 2-5A-anti-hTR reduced the viability of seven bladder cancer
      cell lines (UM-UC-2, UM-UC-3, UM-UC-6, UM-UC-9, UM-UC-14, RT4 and T24) expressing
      telomerase activity to 21-55% within 4 days. The cytotoxicity was mainly due to
      induction of caspase-dependent apoptosis. In contrast, normal fibroblast WI38
      cells lacking telomerase activity were resistant to the treatment. Furthermore,
      treatment of subcutaneous UM-UC-2 tumors in nude mice with 2-5A-anti-hTR
      significantly suppressed the tumor growth through induction of apoptosis (P <
      0.001). These findings may offer a strong support to the feasibility of the 2-5A
      anti-hTR treatment for human bladder cancer.

PMID- 11320415
TI  - The production of mixed cultures containing strains of Lactococcus lactis,
      Leuconostoc cremoris and Lactobacillus rhamnosus, on commercial starter media.
AB  - Mixed starters containing Lactococcus lactis, Leuconostoc cremoris and
      Lactobacillus rhamnosus strains were produced on commercial starter media (MB
      Complete, Thermolac, Marlac), as well as on milk. With the exception of Marlac,
      the starters were cultured under pH control. The effect of media and incubation
      temperature (22 or 32 degrees C) on population ratios, on specific acidifying
      activities (SAA) of the cultures as well as on their ability to produce aroma
      compounds in milk was studied. The starters had higher contents in lactobacilli
      when they were produced at 32 degrees C, whereas a tendency to obtain higher
      Leuconostoc populations was observed at 22 degrees C. With respect to the
      lactococci, there was a significant interaction between temperature and growth
      medium for both strains. Thus, Le. cremoris T2 reached higher populations at 32
      degrees C if grown in MB complete and Thermolac, whereas in Marlac and skim milk,
      viable counts were higher at 22 degrees C. The lactococci represented 50% of the
      total population of the culture at the beginning of the incubation, but they
      composed between 80% and 99% of the total population following fermentation. The
      best medium for growth of Leuconostoc was milk, but populations of only 10(8)
      cfu/ml were reached. The lactobacilli did not grow well in MB Complete, and their
      development was best in the low-phosphate Marlac medium. The cultures grown on
      Marlac had the highest SAA values, whereas those grown on MB complete had the
      lowest. Overall, more ethanol and diacetyl were detected in the fermented milks
      when the starters used to inoculate them were produced at 22 degrees C.

PMID- 11320416
TI  - Citric and gluconic acid production from fig by Aspergillus niger using solid
      state fermentation.
AB  - The production of citric and gluconic acids from fig by Aspergillus niger ATCC
      10577 in solid-state fermentation was investigated. The maximal citric and
      gluconic acids concentration (64 and 490 g/kg dry figs, respectively), citric
      acid yield (8%), and gluconic acid yield (63%) were obtained at a moisture level
      of 75%, initial pH 7.0, temperature 30 degrees C, and fermentation time in 15
      days. However, the highest biomass dry weight (40 g/kg wet substrate) and sugar
      utilization (90%) were obtained in cultures grown at 35 degrees C. The addition
      of 6% (w/w) methanol into substrate increased the concentration of citric and
      gluconic acid from 64 and 490 to 96 and 685 g/kg dry fig, respectively.

PMID- 11320417
TI  - Purification, cloning, and characterization of an arylsulfotransferase from the
      anaerobic bacterium Eubacterium rectale IIIH.
AB  - A bacterium, Eubacterium rectale IIIH, which possessed arylsulfotransferase
      (ASST) activity was isolated from human feces. The ASST gene (astA) was cloned
      and the corresponding protein partially characterized. This gene shows only
      moderate homology to the previously sequenced ASST genes of Klebsiella and
      Enterobacter, which are very closely related to each other.

PMID- 11320418
TI  - Development of an Escherichia coli expression system and thermostability
      screening assay for libraries of mutant xylanase.
AB  - A thermostability screening assay was developed using an Escherichia coli
      expression system to express Streptomyces lividans xylanase A (XlnA). The
      screening system was tested using mutants randomized at position 49 of the S.
      lividans XlnA gene, a position previously shown to confer thermostability with a
      I49P point mutation. The library was cloned into an E. coli expression vector and
      transformed into XL1-blue bacteria. The resulting clones were screened for
      increased thermostability with respect to wild-type XlnA. Using this assay, we
      isolated the I49P mutant previously shown to be thermostable, as well as novel
      I49A and I49C mutants. The I49A and I49C mutants were shown to have 2.8- to 8
      fold increase in thermostability over that of wild-type XlnA. The results show
      that the screening assay can selectively enrich for clones with increased
      thermostability and is suitable for screening small- to medium-sized libraries of
      5000-20,000 clones.

PMID- 11320419
TI  - Inhibitors of farnesylation of Ras from a microbial natural products screening
      program.
AB  - Mutant ras oncogenes are associated with various human tumors such as pancreas,
      colon, lung, thyroid, bladder and several types of leukemia. Prenylation of Ras
      proteins plays a major role in cell proliferation of both normal and cancerous
      cells. Normal and oncogenic Ras proteins are posttranslationally modified by a
      farnesyl group that promotes membrane binding. Inhibitors of farnesyl protein
      transferase (FPTase), the enzyme that catalyzes the prenylation of Ras proteins,
      inhibit growth of tumor cells. In an effort to identify structurally diverse and
      unique inhibitors of FPTase, a program devoted to screening of natural products
      was initiated. This effort led to the identification of 10 different families of
      compounds, all of which selectively inhibit FPTase with a variety of mechanisms
      that are reviewed in this manuscript. These compounds originated from the
      fermentations of a number of microorganisms, either actinomycetes or fungi,
      isolated from different substrates collected in tropical and temperate areas. A
      chemotaxonomic discussion on the distribution of each compound among single or
      different types of microorganisms, either phylogenetically related or unrelated
      species, is included.

PMID- 11320420
TI  - The carboxylic acid reduction pathway in Nocardia. Purification and
      characterization of the aldehyde reductase.
AB  - Whole cultures of Nocardia sp. NRRL 5646 reduce carboxylic acids, first to
      aldehydes, then to alcohols and subsequently to the corresponding acetyl esters.
      This work describes an NADPH-dependent reductase responsible for catalyzing the
      reduction of aldehyde intermediates, which was purified 3240-fold by a
      combination of Mono-Q, hydroxyapatite, and ADP-agarose chromatographies. By
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the purified enzyme
      ran as a single band of 47 kDa. A native molecular mass estimated at 101 kDa
      indicated that the enzyme was a homodimer in the native, active state. Edman
      degradation indicated a unique N-terminal sequence as NH(2)-X-X-Ala-Ala-Ala-Tyr
      Ala-Val-Pro-Ala-Pro-Asp-Gly-Cys-Phe-Glu-Lys-Val-Thr-Ile-Glu-Arg-Arg-Glu-Leu-Gly.
      The enzyme catalyzed reductions of many aryl- and alkyl-aldehyde substrates.
      Reactions were most favorable in the direction of aldehyde reduction to alcohols.

PMID- 11320421
TI  - Characterization of an echinocandin B-producing strain blocked for
      sterigmatocystin biosynthesis reveals a translocation in the stcW gene of the
      aflatoxin biosynthetic pathway.
AB  - Echinocandin B (ECB), a lipopolypeptide used as a starting material for chemical
      manufacture of the anti-Candida agent LY303366, is produced by fermentation using
      a strain of Aspergillus nidulans. In addition to ECB, the wild-type strain also
      produces a significant level of sterigmatocystin (ST), a potent carcinogen
      structurally related to the aflatoxins. Characterization of a mutant designated
      A42355-OC-1 (OC-1), which is blocked in ST biosynthesis, was the result of a
      chromosomal translocation. The chromosomal regions containing the breakpoints of
      the translocation were isolated and DNA sequencing and PCR analysis of the
      chromosomal breakpoints demonstrated the translocation occurred within the stcW
      gene of the ST biosynthetic pathway, resulting in disruption of the open reading
      frame for this gene. Biochemical feeding studies indicate the involvement of this
      gene product in the conversion of averufin to 1-hydroxy versicolorone. This work
      demonstrates an effective synergy between classical strain improvement methods
      and molecular genetics.

PMID- 11320422
TI  - LC-NMR: a new tool to expedite the dereplication and identification of natural
      products.
AB  - The rapid identification of known or undesirable compounds from natural products
      extracts - "dereplication" - is an important step in an efficiently run natural
      products discovery program. Dereplication strategies use analytical techniques
      and database searching to determine the identity of an active compound at the
      earliest possible stage in the discovery process. In the past few years, advances
      in technology have allowed the development of tandem analytical techniques such
      as liquid chromatography mass spectrometry (LC-MS), LC-MS-MS, liquid
      chromatography nuclear magnetic resonance (LC-NMR), and LC-NMR-MS. LC-NMR,
      despite its lower sensitivity as compared to LC-MS, provides a powerful tool for
      rapid identification of known compounds and identification of structure classes
      of novel compounds. LC-NMR is especially useful in instances where the data from
      LC-MS are incomplete or do not allow confident identification of the active
      component of a sample. LC-NMR has been used to identify the marine alkaloid
      aaptamine as the active component in an extract of the sponge Aaptos sp. This
      extract had been identified as an enzyme inhibitor by a high throughput screening
      (HTS) effort. Isolated aaptamine exhibited an IC(50)=120 uM against this enzyme.
      Strategies for the identification of aaptamine and for the use of LC-NMR in a
      natural products HTS program are discussed.

PMID- 11320430
TI  - Performance of compensation seeking and non-compensation seeking samples on the
      Victoria symptom validity test: cross-validation and extension of a
      standardization study.
AB  - Previous research suggests that the Victoria Symptom Validity Test (VSVT) is
      effective in confirming or disconfirming the validity of a patient's reported
      cognitive impairments. We sought to cross-validate the findings of the VSVT
      standardization study, and to determine cut-off scores that are most efficient in
      discriminating our samples of compensation-seeking patients, primarily with mild
      traumatic brain injury (CS; n = 53), and non-compensation seeking patients with
      intractable seizures (NCS; n = 30). All patients in the NCS sample scored in the
      "valid" range on the VSVT difficult memory items, compared to only 58.5% of the
      CS sample. We also identified VSVT measures and cut-off scores maximally
      efficient in discriminating these samples. This study confirms previous research
      that non-compensation seeking patients do well on the VSVT, but that many
      compensation seeking patients perform poorly on this measure.

PMID- 11320431
TI  - A personal floor effect strategy to evaluate the validity of performance on
      memory tests.
AB  - Four methods of assessing the validity of performance on a word recognition test
      were compared among 609 criminal defendants engaged in competency-to-stand-trial
      evaluations. One of the methods, the "normative" floor effect strategy, involves
      comparing an individual's performance to the average performance of individuals
      with true memory impairment. In this sample, 16.9% of defendants performed below
      the normative floor for individuals with true impairment. Another method, the
      "personal" floor effect strategy, identifies performance as suspect when
      individuals perform below a level for which they themselves have already
      demonstrated intact ability. In this sample, the personal floor effect strategy
      identified fewer instances of suspicious performance (15.6%), but the strategy
      may be less sensitive to true memory impairment than the normative floor effect.
      Consequently, the personal floor effect strategy may be more compelling as
      evidence of poor effort or bad intentions on memory testing. Convergent validity
      of the personal floor effect strategy is demonstrated over four analyses.

PMID- 11320432
TI  - A study of three cases of familial related agenesis of the corpus callosum.
AB  - This paper provides data on a family in which three members, all female, have
      been diagnosed as having agenesis of the corpus callosum. That all three
      acallosal individuals came from the same family and showed relatively uniform
      neuropsychological impairment and could be compared in similar terms with their
      "callosal" siblings, also female, provides a unique sample. Inter-hemispheric
      transfer, psychometric measures, and motor and cognitive function were examined
      in the acallosal individuals, all of whom had borderline to low-average
      intelligence, with results compared to their non-acallosal siblings. The data
      indicated that all acallosal individuals exhibited deficits with the cognitive
      tests indicating difficulties of inter-hemispheric transfer of tactile
      information, difficulties in some areas of memory and, at least as far as the
      children are concerned, a marked difference in Verbal IQ and Performance IQ.

PMID- 11320433
TI  - ERP indices of resource allocation difficulties in mild head injury.
AB  - This study examined the hypothesis that distractibility is a characteristic
      sequela of mild closed head injury (MHI). The Minnesota Multiphasic Personality
      Inventory (MMPI-2) was used to study whether comorbid stress-related symptoms are
      associated with behavioral and electrophysiological indexes of attention. Event
      related potentials (ERPs) and performance (reaction time, accuracy) were studied
      in patients with MHI (n = 20), patients with frontal lesions (n = 14), and
      healthy controls (n = 20) during a three-tone oddball task. Participants were
      instructed to detect rare target (2000 Hz) tones, and to withhold responding to
      equally rare distractor (500 Hz) tones and frequently occurring standard (1000
      Hz) tones. All groups distinguished the two classes of deviants as indicated by
      the larger P3 amplitude to target relative to distractor tones. This indicates
      that the group with MHI was capable of differential allocation of attentional
      resources to target and non-target events. However, impaired performance and
      attenuated ERP amplitudes to both classes of deviants relative to patients with
      frontal lesions and controls, suggest limited availability, or expenditure of the
      resources needed for adequate task performance. In the group with MHI, both P3
      amplitude and reaction time (RT) were significantly related to subjectively
      reported distress. The difference in RT disappeared, whereas the P3 amplitude
      differences between the patient groups remained when adjusting for level of
      distress.

PMID- 11320434
TI  - Using the WMS-III to detect malingering: empirical validation of the rarely
      missed index (RMI).
AB  - To detect malingering during memory assessment, we evaluated item response biases
      to the Logical Memory Delayed Recognition (LMDR) subtest of the WMS-III. In a
      sample of 50 healthy volunteers who were completely naive to the content of the
      Logical Memory stories, 6 LMDR items were correctly endorsed above chance
      probabilities. These 6 rarely missed items significantly discriminated 51
      patients with neurological impairment from 36 volunteers who attempted to feign
      head injury and poor cognitive performance. A weighted combination of the 6 items
      was summed to form a single Rarely Missed Index (RMI). The RMI accurately
      classified over 98% of participants and demonstrated high sensitivity (97%) and
      specificity (100%) in discriminating between analog malingerers and patients.
      Because the RMI is calculated directly from the LMDR items, it has the advantage
      of requiring no additional administration time or materials, and thus may serve
      as a quick screen for dissimulation that can be obtained without additional
      testing.

PMID- 11320435
TI  - Trail making across languages.
AB  - The effects of different language backgrounds on trail making tasks were examined
      in this study. The measures adopted were the Color Trails Test (CTT) and the
      Trail Making Test (TMT), the former being the culturally fair analogue of the
      latter. Eighty-four right-handed participants belonging to the Chinese-English
      Bilingual (CEB) and English Monolingual (EM) groups participated in this study.
      The results of between-group comparisons revealed no significant differences in
      performance on the two measures between our Chinese bilingual and English
      monolingual participants, except on the TMT-A. However, a within-group
      correlation indicated that performances on the TMT and CTT were highly correlated
      for the English sample, but not for the Chinese. These observations suggest that
      trail making tasks like the TMT and CTT are themselves generally fair across
      Chinese and English, but equivalence between them may be more language-specific.
      Furthermore, mastery of a language loaded on temporal sequencing like English may
      give an advantage in the completion of trail making tasks.

PMID- 11320436
TI  - The relationship between CVLT-C process scores and measures of executive
      functioning: lack of support among community-dwelling adolescents.
AB  - In an effort to characterize how a child goes about learning and recalling
      information, the developers of the California Verbal Learning Test for Children
      (CVLT-C) provided normative data related to both learning outcome and learning
      process. The present study examined the assertion that CVLT-C process indices
      relate to executive functioning in a sample of community-dwelling adolescents.
      Contrary to predictions, measures of executive functioning typically correlated
      poorly with measures of learning process, despite displaying significant
      correlations with measures of learning outcome. Although further research is
      recommended, these findings do not support the clinical interpretation of CVLT-C
      process indices as reflections of executive functioning.

PMID- 11320437
TI  - Test-retest performance for the consonant-vowel dichotic listening test with and
      without attentional manipulations.
AB  - The present work aimed to replicate Hugdahl and Hammar's (1997) study on the
      reliability of dichotic listening under divided or focused attention conditions.
      With the same consonant-vowel syllable dichotic listening procedure, 16 subjects
      were tested twice, 2 weeks apart. The design included a condition without
      attentional instructions (nonforced) and two conditions with the instruction to
      attend either to the right- or the left-ear input. The results showed a
      significant correlation coefficient of.82 for the standard nonforced condition,
      indicating temporal stability for the ear advantages. There were also high
      correlation coefficients for the focused attention conditions (.77 and.76),
      although the subjects performed the attentional instructions more accurately in
      session two.

PMID- 11320438
TI  - Profiles of cognitive performance associated with reading disability in temporal
      lobe epilepsy.
AB  - 92 patients with temporal lobe epilepsy (TLE) were classified into reading
      deficient (RD; N = 41) and non-reading deficient (no-RD; N = 51) groups. A cutoff
      of 80 was used to further classify patients as having low average or better (AVG:
      IQ > 79) or below average (LOW: 69 < IQ < 80) intellectual ability. Differences
      between RD-AVG and no-RD-AVG patients in profiles of performance on cognitive
      tests were specific to verbal and non-verbal memory and verbal abilities, but not
      visuoconstructional and executive abilities. RD-LOW patients exhibited globally
      reduced abilities. Profiles of performance on cognitive tests were sensitive to
      side of seizure onset in the no-RD AVG group, but not the RD-AVG or RD-LOW
      groups. These data suggest that a group of patients with TLE and reduced academic
      achievement exhibit cognitive deficits suggestive of a language learning
      disability, and that cognitive tests are less sensitive to side of seizure onset
      in this group.

PMID- 11320439
TI  - Word frequency and word stem completion in Korsakoff patients.
AB  - Korsakoff patients are generally agreed to be impaired in conscious recollection,
      but whether their implicit memory performance is also affected is less certain. A
      deficit in novelty dependent encoding (i.e., elaboration learning) could account
      for both types of impairments and predicts a reduced implicit word frequency
      effect in the patients. This effect was examined with word stem completion in
      nineteen Korsakoff patients and nineteen healthy controls. The word frequency
      effect was larger in controls than in patients in absolute terms, but not
      reliably so. It is concluded that elaboration learning may be spared to some
      degree in Korsakoff amnesia, but, in line with the original reasoning by
      Korsakoff (1889/1996), it may only be engaged by the patients when they are
      continuously prompted to do so.

PMID- 11320440
TI  - Confrontation naming of environmental sounds.
AB  - The development of a set of everyday, nonverbal, digitized sounds for use in
      auditory confrontation naming applications is described. Normative data are
      reported for 120 sounds of varying lengths representing a wide variety of
      acoustic events such as sounds produced by animals, people, musical instruments,
      tools, signals, and liquids. In Study 1, criteria for scoring naming accuracy
      were developed and rating data were gathered on degree of confidence in sound
      identification and the perceived familiarity, complexity, and pleasantness of the
      sounds. In Study 2, the previously developed criteria for scoring naming accuracy
      were applied to the naming responses of a new sample of subjects, and oral naming
      times were measured. In Study 3 data were gathered on how subjects categorized
      the sounds: In the first categorization task - free classification - subjects
      generated category descriptions for the sounds; in the second task - constrained
      classification - a different sample of subjects selected the most appropriate
      category label for each sound from a list of 27 labels generated in the first
      task. Tables are provided in which the 120 stimuli are sorted by familiarity,
      complexity, pleasantness, duration, naming accuracy, speed of identification, and
      category placement. The. WAV sound files are freely available to researchers and
      clinicians via a sound archive on the World Wide Web; the URL is
      http://www.cofc.edu/~marcellm/confront.htm.

PMID- 11320441
TI  - Learning impairment is associated with recall ability in multiple sclerosis.
AB  - Recent evidence suggests that persons with multiple sclerosis may experience
      deficits in verbal and visuospatial acquisition rather than recall. The present
      study was designed to determine whether this finding generalized to a broader
      range of neuropsychological tests of learning and memory. To control for group
      differences in information acquisition, healthy controls (HCs) and persons with
      multiple sclerosis (MS) were trained to specific learning criteria on both verbal
      (i.e., paragraph learning and paired associates) and visuospatial (i.e., facial
      recognition) memory tasks. Persons with MS required significantly more learning
      trials to meet criteria on the paragraph learning and facial recognition tasks,
      but not the paired associates test. However, after learning comparable amounts of
      information, the MS and HC groups recalled statistically similar amounts of
      information at 30-minutes, 90-minutes, and up to 1-week on the paragraph learning
      and paired associate tests. This suggests that persons with MS may have deficits
      in acquisition rather than recall per se. Results are discussed in terms of
      possible rehabilitation strategies to improve memory functioning in persons with
      MS.

PMID- 11320442
TI  - Advances in functional neuroimaging methodology for the study of brain systems
      underlying human neuropsychological function and dysfunction.
AB  - Functional neuroimaging allows the non-invasive identification of distributed
      patterns of human brain activity associated with perceptual, congnitive,
      emotional and behavioral processes, in health and disease. Work in this field is
      methodologically intensive, requiring an interdisciplinary team of scientists to
      develop and apply rapidly advancing techniques. Here we focus upon the principles
      and methods of functional imaging, from hypothesis generation and study design,
      to subject recruitment and clinical characterization, neuropsychological paradigm
      development, image acquisition, image processing and statistical analysis, and
      data interpretation. The strengths and limitations of the various techniques are
      discussed, with an emphasis on positron emission tomography (PET) and functional
      magnetic resonance imaging (fMRI), which have proven to be powerful tools for
      human brain mapping. The integration of these techniques with
      electroencephalography (EEG) and magnetoencephalography (MEG), which provide
      greater temporal information, is outlined. An understanding of such
      methodological issues is a necessary prerequisite to the development of new
      imaging methods with improved capabilities, to the careful application of
      existing methods to neuropsychological problems, and to the critical examination
      of planned or published studies.

PMID- 11320443
TI  - Bridging the gap between neuroimaging and neuropsychology: using working memory
      as a case-study.
AB  - Neuropsychology and neuroimaging both provide information about the relationship
      between brain structure and function, and thus attempt to understand if the
      neural basis of cognition should benefit from converging results obtained across
      the two methods. However, serious attempts to integrate the two methodologies
      face several challenges, such as differences in basic paradigm designs. To
      illustrate these points, this article will review neuropsychological and
      neuroimaging research in the area of working memory. Points of discussion will
      include discrepancies between neuropsychological and neuroimaging evidence for
      domain-specific rehearsal systems, the role of left inferior parietal cortex in
      phonological storage, and the contributions of Brocas area and the cerebellum to
      articulatory rehearsal. Methodological factors and assumptions that may account
      for these discrepancies, and the steps that could be taken to overcome them, will
      be evaluated. The overall objective of this "case study" is to encourage
      neuroimagers and neuropsychologists to evaluate seriously the results obtained in
      both methodologies when formulating interpretations of their data and when
      designing new studies.

PMID- 11320444
TI  - Functional neuroimaging and episodic memory: a perspective.
AB  - One area of research that has significantly benefited from the recent development
      of functional neuroimaging techniques is the study of memory. In this review we
      explore what has been learned about the neural basis of normal memory function
      using these techniques. We focus on episodic memory, which is characterized by
      the ability to consciously recollect memories for facts or events. We highlight
      three neuroanatomical regions that have been linked to episodic memory: The
      hippocampal complex, the prefrontal cortex and the amygdala. For each of these
      regions, we discuss the behavioral methods of assessment and specific episodic
      memory processes, particularly encoding and retrieval. Finally, we briefly
      comment on the potential clinical applications for this research and other memory
      systems.

PMID- 11320445
TI  - Language and brain: what is up? What is coming up?
AB  - The classical aphasiological model of brain/language relationships is nowadays
      complemented by independent results from functional neuroimaging studies using
      techniques such as Positron Emission Tomography, functional Magnetic Resonance
      Imaging, or Event-Related Electro-Encephalography and Magneto-Encephalography
      mapping. Although brain mapping of language is still hampered by many
      methodological pitfalls, these methods now appear reliable and provide a renewed
      description of the temporal spatial dynamics of neural ensembles subserving
      language functions. Moreover, neuroimaging techniques should also shed a new
      light on remaining difficult issues such as neural and functional plasticity in
      developmental or post-lesional contexts.

PMID- 11320446
TI  - Brain imaging of attentional networks in normal and pathological states.
AB  - The ability to image the human brain has provided a new perspective for
      neuropsychologists in their efforts to understand, diagnose, and treat insults to
      the human brain that might occur as the result of stroke, tumor, traumatic
      injury, degenerative disease, or errors in development. These new findings are
      the major theme of this special issue. In our article, we consider brain networks
      that carry out the functions of attention. We outline several such networks that
      have been studied in normal and pathological states. These include networks for
      orienting to sensory stimuli, for maintaining the alert state, and for
      orchestrating volitional control. There is evidence that these networks have a
      certain degree of anatomical and functional independence, but that they also
      interact in many practical situations. Damage to each of these networks,
      irrespective of the source, produces distinctive neuropsychological deficits. We
      consider the links between the etiology of the injury and changes in cognition
      and behavior and examine the role of brain imaging in the study of
      rehabilitation.

PMID- 11320447
TI  - Functional neuroimaging of human central auditory processing in normal subjects
      and patients with neurological and neuropsychiatric disorders.
AB  - Auditory sensory processing in the human cerebral cortex is disturbed in several
      neurological and neuropsychiatric disorders, ranging from devastating perceptual
      deficits in neuropsychological syndromes such as cortical deafness and auditory
      agnosia to the problem of involuntary hallucinatory perception in schizophrenia.
      With modern non-invasive functional imaging techniques (e.g., PET, fMRI, and
      MEG), the normal auditory cortical functional anatomy can now be studied in
      humans in vivo, as well as its disruption in pathological conditions. This
      article will summarize current knowledge on human central auditory perception in
      health and disease, with an emphasis on recent functional neuroimaging studies,
      in the context of clinical and basic neuroscientific knowledge. New strategies
      include a focus on the role of other, non-temporal brain areas for auditory
      processing, particularly in the frontal lobes, and the combined use of techniques
      offering both precise spatial and temporal resolution. One step towards this goal
      has been the recent development of a silent, event-related fMRI scanning
      technique.

PMID- 11320448
TI  - The role of functional neuroimaging in the neuropsychology of depression.
AB  - Depressed individuals show impaired performance in tests of attention and
      concentration. They also exhibit PET resting state abnormalities in dorsal
      prefrontal cortex and anterior cingulate, regions known to be substrates of
      attentional processing in healthy individuals. This chapter outlines a strategy
      to study neuropsychological mechanisms in emotional disorders using functional
      imaging methods. It reviews evidence strongly implicating the dorsolateral
      prefrontal cortex, particularly in the right hemisphere, as a key brain structure
      in emotion/cognition interactions in negative mood states. It will be argued that
      this neocortical region is a crucial convergence zone, being the substrate of
      sustained attention to the external environment, and the main target of limbic
      cortical influences during changes in mood state across health and disease.

PMID- 11320449
TI  - Worldwide prevalence of antimicrobial resistance in Streptococcus pneumoniae,
      Haemophilus influenzae, and Moraxella catarrhalis in the SENTRY Antimicrobial
      Surveillance Program, 1997-1999.
AB  - The in vitro activities of numerous antimicrobials against clinical isolates of
      Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis from
      patients with bloodstream and respiratory tract infections in the United States,
      Canada, Europe, Latin America, and the Asia-Pacific region were studied in the
      SENTRY Antimicrobial Surveillance Program. Penicillin resistance (minimum
      inhibitory concentration, > or =2 microg/mL) was noted in all 5 geographic
      regions, and a high and increasing rate of macrolide resistance among S.
      pneumoniae isolates was observed. Elevated rates of resistance to clindamycin,
      trimethoprim-sulfamethoxazole, chloramphenicol, and tetracycline were seen. beta
      Lactamase-mediated resistance in H. influenzae to amoxicillin and variable
      trimethoprim-sulfamethoxazole resistance by region were documented. Resistance to
      several drugs continues to emerge among pneumococci worldwide, but more stable
      resistance patterns have been noted for H. influenzae and M. catarrhalis.
      Continued surveillance of this pathogen group appears to be prudent.

PMID- 11320450
TI  - Variations in the prevalence of strains expressing an extended-spectrum beta
      lactamase phenotype and characterization of isolates from Europe, the Americas,
      and the Western Pacific region.
AB  - To evaluate the prevalence of extended-spectrum beta-lactamase (ESBL)-producing
      strains among species of Enterobacteriaceae, a microdilution susceptibility test
      was performed with strains of Klebsiella pneumoniae, Escherichia coli, Proteus
      mirabilis, and Salmonella species that were isolated as part of the SENTRY
      project. The highest percentage of ESBL phenotype (defined as a minimum
      inhibitory concentration [MIC] > or =2 microg/mL for ceftazidime, ceftriaxone, or
      aztreonam) was detected among K. pneumoniae strains from Latin America (45%),
      followed by those from the Western Pacific region (25%), Europe (23%), the United
      States (8%), and Canada (5%). P. mirabilis and E. coli strains for which MICs of
      extended-spectrum cephalosporins or monobactams were elevated also were more
      prominent in Latin America. Testing with ceftazidime revealed more isolates with
      elevated MICs than did testing with ceftriaxone or aztreonam. ESBL strains showed
      high levels of co-resistance to aminoglycosides, tetracycline, trimethoprim
      sulfamethoxazole, and ciprofloxacin. Imipenem remains highly effective against
      ESBL strains. Organisms expressing an ESBL are widely distributed worldwide,
      although prevalence rates are significantly higher in certain geographic regions.

PMID- 11320451
TI  - Emerging importance of multidrug-resistant Acinetobacter species and
      Stenotrophomonas maltophilia as pathogens in seriously ill patients: geographic
      patterns, epidemiological features, and trends in the SENTRY Antimicrobial
      Surveillance Program (1997-1999).
AB  - As part of the SENTRY Antimicrobial Surveillance Program, a total of 1078
      Acinetobacter species and 842 Stenotrophomonas maltophilia isolates were
      collected between January 1997 and December 1999 from 5 geographic regions
      (Canada, the United States, Latin America, Europe, and the Asia-Pacific). The
      frequency of infections (by geographic region and body site), including those due
      to imipenem-resistant Acinetobacter species and trimethoprim-sulfamethoxazole
      (TMP-SMZ)-resistant S. maltophilia, was evaluated. The possibility of seasonal
      variations in bloodstream infections caused by Acinetobacter species was studied,
      as was the activity of several therapeutic antimicrobials against all strains.
      Acinetobacter species and S. maltophilia were most frequently associated with
      pulmonary infections, independent of the region evaluated. In contrast, patterns
      of antimicrobial resistance markedly varied among distinct geographic regions,
      especially for nosocomial isolates. Although the carbapenems were the most active
      antimicrobials against Acinetobacter species, nearly 11.0% of the nosocomial
      isolates were resistant to this drug group in both regions. TMP-SMZ, ticarcillin
      clavulanic acid, gatifloxacin, and trovafloxacin were the only agents with
      consistent therapeutic activity against S. maltophilia isolates. Rates of
      resistance to TMP-SMZ ranged from 2% in Canada and Latin America to 10% in
      Europe. The geographic differences in resistance patterns among Acinetobacter
      species and S. maltophilia isolates observed in this study emphasize the
      importance of local surveillance in determining the most adequate therapy for
      acinetobacter and S. maltophilia infections and the possible clonal, epidemic
      nature of occurrence.

PMID- 11320452
TI  - Survey of infections due to Staphylococcus species: frequency of occurrence and
      antimicrobial susceptibility of isolates collected in the United States, Canada,
      Latin America, Europe, and the Western Pacific region for the SENTRY
      Antimicrobial Surveillance Program, 1997-1999.
AB  - Between January 1997 and December 1999, bloodstream isolates from 15,439 patients
      infected with Staphylococcus aureus and 6350 patients infected with coagulase
      negative Staphylococcus species (CoNS) were referred by SENTRY-participating
      hospitals in the United States, Canada, Latin America, Europe, and the Western
      Pacific region. S. aureus was found to be the most prevalent cause of bloodstream
      infection, skin and soft-tissue infection, and pneumonia in almost all geographic
      areas. A notable increase in methicillin (oxacillin) resistance among community
      onset and hospital-acquired S. aureus strains was observed in the US centers. The
      prevalence of methicillin (oxacillin)-resistant S. aureus varied greatly by
      region, site of infection, and whether the infection was nosocomial or community
      onset. Rates of methicillin resistance were extremely high among S. aureus
      isolates from centers in Hong Kong and Japan. Uniformly high levels of
      methicillin resistance were observed among CoNS isolates. Given the increasing
      multidrug resistance among staphylococci and the possible emergence of vancomycin
      resistant strains, global strategies are needed to control emergence and spread
      of multiply resistant staphylococci.

PMID- 11320453
TI  - Clinical prevalence, antimicrobial susceptibility, and geographic resistance
      patterns of enterococci: results from the SENTRY Antimicrobial Surveillance
      Program, 1997-1999.
AB  - As part of the SENTRY Antimicrobial Resistance Surveillance Program, a total of
      4998 strains of enterococci isolated from 1997 to 1999 were processed. The
      occurrence of enterococcal infections by species and site of infection was
      analyzed, as were the occurrence of vancomycin-resistant enterococci (VRE) and
      their resistance phenotypes and genotypes. Trends in antimicrobial susceptibility
      to a variety of agents (including experimental compounds) were also reported.
      Enterococci accounted for >9% of isolates from all bloodstream infections (BSIs)
      in North America. Ampicillin was active against strains from Latin America and
      Europe but not against those from the United States and Canada. US isolates were
      considerably more resistant to vancomycin (17% resistant strains in 1999) than
      were those from patients in the rest of the world. The highest proportion of VRE
      was observed among BSI isolates (81.7%). Quinupristin-dalfopristin,
      chloramphenicol, and doxycycline were the most active agents tested against VRE.
      The results of this study confirm the worldwide trend in increasing occurrence of
      enterococci and the emerging pattern of antimicrobial resistance among such
      isolates.

PMID- 11320454
TI  - Characterization of Pseudomonas aeruginosa isolates: occurrence rates,
      antimicrobial susceptibility patterns, and molecular typing in the global SENTRY
      Antimicrobial Surveillance Program, 1997-1999.
AB  - During 1997-1999, a total of 70,067 isolates (6631 Pseudomonas aeruginosa
      isolates) were analyzed in the SENTRY program by geographic region and body site
      of infection. The respiratory tract was the most common source of P. aeruginosa.
      P. aeruginosa isolation rates increased during the study interval. Europe was the
      only region to show a significant decline in beta-lactam and aminoglycoside
      susceptibility rates. There was a reduction in the rates of susceptibility of
      Canadian isolates to imipenem and of Latin American isolates to meropenem. A
      total of 218 multidrug-resistant P. aeruginosa isolates (MDR-PSA; resistant to
      piperacillin, ceftazidime, imipenem, and gentamicin) were observed; MDR-PSA
      occurrence rates (percentages of all isolates) ranged from 8.2% (Latin America)
      to 0.9% (Canada). No antimicrobial inhibited >50% of MDR-PSA strains. Molecular
      characterization of selected, generally resistant strains was performed. Isolates
      showing unique ribogroups were found in Europe, Latin America, and the United
      States, but clonal spread was documented in several medical centers.

PMID- 11320455
TI  - Integration of molecular characterization of microorganisms in a global
      antimicrobial resistance surveillance program.
AB  - The SENTRY Antimicrobial Surveillance Program has incorporated molecular strain
      typing and resistance genotyping as a means of providing additional information
      that may be useful for understanding pathogenic microorganisms worldwide.
      Resistance phenotypes of interest include multidrug-resistant pathogens, extended
      spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae, methicillin
      resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci, and
      fluoroquinolone-resistant (FQR) strains of gram-negative bacilli and
      Streptococcus pneumoniae. Clusters of > or =2 isolates within a given resistance
      profile that are linked temporally and by hospital location are flagged for DNA
      fingerprinting. Further characterization of organisms with respect to resistance
      genotype is accomplished with use of polymerase chain reaction and DNA
      sequencing. This process has been highly successful in identifying clonal spread
      within clusters of multiresistant pathogens. Between 50% and 90% of MRSA clusters
      identified by phenotypic screening contained evidence of clonal spread. Among the
      Enterobacteriaceae, ESBL-producing strains of Escherichia coli and Klebsiella
      pneumoniae are the most common pathogens causing clusters of infection, and
      approximately 50% of recognized clusters demonstrate clonal spread. Clusters of
      Pseudomonas aeruginosa, Acinetobacter species, and Stenotrophomonas maltophilia
      have been noted with clonal spread among patients with urinary tract,
      respiratory, and bloodstream infections. Characterization of mutations in the FQR
      determining region of phenotypically susceptible isolates of E. coli and S.
      pneumoniae has identified first-stage mutants among as many as 40% of isolates.
      The ability to characterize organisms phenotypically and genotypically is
      extremely powerful and provides unique information that is important in a global
      antimicrobial surveillance program.

PMID- 11320456
TI  - Independent risk for cardiovascular disease predicted by modified continuous
      score electrocardiographic criteria for 6-year incidence and regression of left
      ventricular hypertrophy among clinically disease free men: 16-year follow-up for
      the multiple risk factor intervention trial.
AB  - Risk prediction for electrocardiographic (ECG) left ventricular hypertrophy
      related criteria, used in clinical trials, and epidemiologic studies of
      clinically healthy people, has depended in the past on dichotomous classification
      of ECG LVH criteria. Recent analyses have shown that more sensitive methods of
      LVH ECG classification without loss of specificity are needed to improve on
      dichotomous classification. This was done by relating six year incident
      significant change in continuous score criteria of ECG LVH to the 16 year (10
      year post trial) coronary heart disease (CHD) and cardiovascular disease (CVD)
      mortality among 12,866 men, free of clinical disease, aged 35 to 57 years at
      baseline in the Multiple Risk Factor Intervention Trial. It was found that
      significant change in continuous ECG LVH criteria was a stronger independent
      predictor of future CHD and CVD mortality than was use of dichotomous
      classification of the same criteria. It was also demonstrated that increase in
      continuous ECG LVH indexes, below previous dichotomous thresholds independently
      (of standard CVD risk factors, including increase in obesity-indicated by an
      increase in adult BMI) predicted excess CHD and CVD mortality and that
      combinations of continuous indices increases the specificity and relative risk in
      clinically disease-free middle-aged men.

PMID- 11320457
TI  - Early assessment of long-term risk with continuous ST-segment monitoring among
      patients with unstable coronary syndromes. Results from 1-year follow-up in the
      TRIM study.
AB  - A total of 323 patients who took part in the TRIM trial underwent an initial 24 h
      continuous electrocardiogram ST-segment monitoring. A ST vector magnitude (ST-VM)
      maximum > or = 144 microV predicted death or myocardial infarction within 1 year
      with a 78% specificity and a 52% sensitivity, an area under the ST-VM trend curve
      > or = 162 mu with a 86% specificity and a 42% sensitivity and presence of ST-VM
      episodes with a 70% specificity and a 68% sensitivity. Patients who had neither
      ST-VM episodes nor a ST-maximum > or = 144 microV had only a 4.5% incidence of
      death or myocardial infarction within one year as compared to 18% among those
      patients who met any of these criteria. ST-segment monitoring with continuous
      vectorcardiography is feasible for risk stratification at least up to 1 year
      after an episode of unstable coronary artery disease and several
      vectorcardiographic parameters may be used.

PMID- 11320458
TI  - Dynamic changes of QT interval and QT dispersion in non-Q-wave and Q-wave
      myocardial infarction.
AB  - QT interval and QT dispersion both prolong early postinfarction. Non-Q wave
      (NQMI) and Q-wave myocardial infarction (QMI) differ in the extent of transmural
      necrosis, which may influence these measures of myocardial repolarization. This
      study compared dynamic changes in QT interval and QT dispersion early
      postinfarction between NQMI and QMI. In 40 patients with NQMI and 69 patients
      with QMI, maximum QTc (QTc(max)) and QT dispersion (QTD) were measured during the
      first 4 days postinfarction. Infarct size was assessed daily by using the
      Selvester QRS score. In both infarct types, QTc(max) and QTD were prolonged on
      day 1 of infarction, peaking over the next 2 days before returning toward
      baseline by day 4. NQMI patients had significantly longer QTc(max) and QTD by
      days 2 to 3 when compared with QMI patients. Multivariable linear regression
      identified "infarct type x QRS score" as the only independent predictor of
      QTc(max) (R(2) =.32, P <.0001) and QTD (R(2) =.19, P <.0001) on day 2. In
      conclusion, dynamic changes of QTc(max) and QTD occur in both infarct types.
      Large NQMI is associated with greater prolongation of QTc(max) and QTD, which may
      be due to greater M cell uncoupling and exposure when compared with QMI.

PMID- 11320459
TI  - QT and JT dispersion in patients with monomorphic or polymorphic ventricular
      tachycardia/ventricular fibrillation.
AB  - The present study evaluates the repolarization abnormalities in patients with
      monomorphic sustained ventricular tachycardia (MVT) and polymorphic ventricular
      tachycardia/ventricular fibrillation (PMVT/VF) by measuring QT and JT dispersion
      on the surface electrocardiogram (ECG). QT dispersion is a predictor of
      ventricular arrhythmias in several clinical settings. However, the value of QT
      and JT dispersion in identifying patients at risk for PMVT/VF is controversial.
      Maximum QT (JT) interval duration and QT (JT) dispersion were compared between 20
      healthy individuals, 12 patients with inducible MVT during programmed electrical
      stimulation and seven patients with PMVT/VF recorded during 24-hour ambulatory
      ECG or induced by programmed electrical stimulation. QT dispersion was 40 +/- 9
      ms in the control group, 63 +/- 21 ms in the MVT group, and 79 +/- 31 ms in the
      PMVT/VF group. QT dispersion in both the MVT and PMVT/VF groups were
      significantly greater than in the control group (P <.001 and P <.0001,
      respectively); however, there was no significant difference between the MVT and
      PMVT/VF groups. JT dispersion was 41 +/- 14 ms in the control group, 69 +/- 14 ms
      in the MVT group and 103 +/- 37 ms in the PMVT/VF group. JT dispersion differed
      significantly between the study groups and was significantly increased in PMVT/VF
      group than in the control group or MVT groups (P <.0001 vs. the control group, P
      <.005 vs. the MVT group). Patients with PMVT/VF have a greater dispersion of
      ventricular repolarization time. Repolarization abnormalities are important for
      ventricular arrhythmogenesis and detectable on the surface ECG.

PMID- 11320460
TI  - Recovery time dispersion measured by body surface mapping: noninvasive method of
      assessing vulnerability to ventricular tachyarrhythmias.
AB  - To assess the significance of recovery time (RT) dispersion measured by body
      surface mapping, we investigated body surface RT isochrone maps of 40 patients
      with anterior old myocardial infarction (OMI), 40 patients with dilated
      cardiomyopathy (DCM), and 40 controls. Among the OMI and DCM groups, 20 patients
      per group had sustained ventricular tachycardia (VT). The dispersion of corrected
      recovery time (RTc) by Bazett's formula significantly increased in OMI patients
      (169 +/- 38 ms) and DCM patients (163 +/- 22 ms) compared with controls (147 +/-
      10 ms) (P <.01). RTc dispersion was greater in OMI patients with sustained VT
      than in those without sustained VT [184 +/- 43 ms vs. 155 +/- 24 ms (P <.05)], as
      well as in DCM patients with sustained VT compared with those without sustained
      VT [170 +/- 25 ms vs. 156 +/- 17 ms (P <.05)]. The results suggest that RTc
      dispersion determined by body surface mapping can be useful for assessing
      vulnerability to sustained VT.

PMID- 11320461
TI  - Alternans of ventricular gradient during percutaneous transluminal coronary
      angioplasty.
AB  - We evaluated the influence of local myocardial ischemia induced by acute coronary
      occlusion during percutaneous transluminal coronary angioplasty (PTCA) on the
      ventricular gradients (VG) and investigated whether 2:1 alternans of VG occurs.
      Twenty-seven patients with angina pectoris, who had one-vessel coronary artery
      stenosis, were studied. The VG of each consecutive heartbeat before, during, and
      after PTCA over a 22-second interval was calculated using a microcomputer. The
      standard deviation and coefficient of variation of magnitude were used as indices
      of VG variability. Frequency-domain analysis of time series consisting of beat-to
      beat VG magnitude for a 22-second interval was also performed by the maximum
      entropy method. The standard deviation and coefficient of variation of VG
      magnitude during PTCA were significantly greater than those before and after PTCA
      (P <.01, P <.01, respectively), and the indices before PTCA were also
      significantly greater than those after PTCA (P <.05). The maximum power spectrum
      peaks around 0.5 cycles/beat during PTCA were significantly greater than those
      after PTCA (P <.01); this suggests that the enhancement of VG alternans is
      reflected by 2:1 alternans of the action potential in the acute local ischemic
      myocardium during PTCA.

PMID- 11320462
TI  - Heart rate decline after exercise in patients with hypertrophic cardiomyopathy.
AB  - To evaluate the heart rate recovery, submaximal exercise, echocardiographic
      examination, and Holter monitoring were performed on 30 patients with
      hypertrophic cardiomyopathy and 11 controls. The time constant of heart rate
      decline after exercise was calculated. Spectral analysis was performed on Holter
      recordings. The time constant did not correlate with heart rate, left ventricular
      end-diastolic pressure, ejection fraction, or wall thickness. There was no
      correlation between the time constant and any mean spectral indices over 24 hours
      in patients. However, the time constant correlated with high frequency component
      in the night. Nocturnal high frequency component in patients with short time
      constant was significantly less than in those with long time constant, but did
      not significantly differ from that in controls. In conclusion, the heart rate
      decline after exercise does not primarily reflect the severity of hypertrophy or
      hemodynamic impairment but is associated with nocturnal parasympathetic
      modulation in patients with hypertrophic cardiomyopathy.

PMID- 11320463
TI  - Diagnosis of myocardial infarction-induced ventricular aneurysm in the presence
      of complete left bundle branch block.
AB  - An analysis of the 4,196 files of our Cardiology Clinic cohort showed 128
      patients with a complete left bundle branch block (LBBB) in their
      electrocardiograms (ECGs). Of these patients, 27 had suffered a myocardial
      infarction in the past and had been found to have a ventricular aneurysm (VA),
      documented by > or = 1 of several noninvasive and invasive diagnostic methods.
      Five of these 27 patients had stable ST-segment elevation in > or = 1 of left
      precordial ECG leads, with predominantly positive QRS complexes (an ECG criterion
      for the diagnosis of VA in the presence of LBBB, which we have recently
      described). The sensitivity of this ECG criterion for the diagnosis of VA was
      18.5%, and the specificity was 100%. The frequency of distribution of VA in the
      septal, and even more, apical myocardial regions was higher in the patients with
      a positive ECG diagnosis of VA, than in the patients with a negative one (P =
      .049, and P = .009, correspondingly). The number of myocardial territories
      involved with a VA was not different in the 2 subgroups (P =.325).
      Pathophysiologically, this ECG alteration diagnostic of VA represents a
      superimposition of the primary ST-segment elevation due to the VA, on the
      expected secondary ST-segment depression due to the LBBB, and represents a
      summation effect.

PMID- 11320464
TI  - The evaluation of a precordial ECG BELT: technologist satisfaction and accuracy
      of recording.
AB  - The standard method for performing electrocardiogram (ECG) recordings presents a
      challenge to technicians because of the need to correctly position the individual
      precordial electrodes according to 6 bony thoracic landmarks. A proposed new
      method using a 6-lead ECG BELT for precordial application was compared to the
      standard method to determine the level of agreement among automated
      interpretations. A comparison of automated interpretations from repeat standard
      recordings served as the control. Results indicate that BELT and standard
      automated interpretations disagreed significantly more frequently than repeat
      standard recording automated interpretations of the cardiac rhythm. The BELT's
      most obvious weakness was the inability to obtain a recording with a stable ECG
      baseline, triggering automated detection of "baseline artifact or wander," and
      requiring a repeat recording. These findings suggest that the ECG BELT is not
      adequate for clinical application in its current form.

PMID- 11320465
TI  - Use of the sinus P wave in diagnosing electrocardiographic limb lead misplacement
      not involving the right leg (ground) lead.
AB  - No general approach has been established for the diagnoses of the various types
      of electrocardiograms of limb lead misplacement not involving the right leg
      (ground) lead. We have developed a 3-step algorithm for such differential
      diagnosis that can be applied without having to rely on the comparison with a
      reference electrocardiogram. It is based on the observation that the frontal
      plane sinus P vector loop is almost invariably inscribed counterclockwise. The 5
      types of electrocardiograms of limb lead misplacement can be differentiated
      according to the P wave axis, the location of the lead aVR in the
      electrocardiogram, and specifically any apparent reversal of the direction of
      inscription of the frontal plane P vector loop due to lead misplacement.
      Characteristic limb lead P wave patterns provide 6 signs capable of inferring
      from the electrocardiogram alone the direction of inscription about 94% of the
      time. P wave axis itself is diagnostic in an additional 4%.

PMID- 11320466
TI  - Giant R-waves in a patient with an acute inferior myocardial infarction.
AB  - We describe a case of a male patient with "giant" R-waves (GRWs) in association
      with an acute inferior myocardial infarction (MI). Such electrocardiogram (ECG)
      pattern has been associated heretofore with the hyperacute phase of an anterior
      MI, and unstable, and variant angina, although it is found in illustrations of
      many previous publications in conjunction with inferior MI. The GRWs, along with
      ST-segment elevations, were noted transiently in the inferior ECG leads, early in
      the clinical course of our patient. Subsequent evolution of the ECG revealed
      classic appearances for an inferior MI. Cardiac enzymes, and thallium-201
      myocardial perfusion scintigraphy revealed evidence for inferiorly-located
      myocardial necrosis. Coronary arteriography showed stenosis of the right coronary
      artery, for which the patient underwent an uneventful angioplasty and "stenting"
      of the culprit vessel. The pathophysiology of the syndrome of GRWs is briefly
      discussed.

PMID- 11320467
TI  - Repetitive supernormal conduction in the right bundle branch in high degree
      bilateral bundle branch block.
AB  - Electrocardiograms were taken from a 67-year-old woman with high-degree
      atrioventricular block in which ventricular escape beats of right bundle branch
      block pattern occurred, accompanying occasional ventricular capture beats. Only
      when a sinus P wave occurred 0.60 s after the preceding escape beat, it was
      followed by a capture beat of left bundle branch block pattern with the RP
      interval of 0.60 s and the PR interval of 0.19 s. Similar left bundle branch
      block with left axis deviation pattern had been shown in the electrocardiogram
      taken 2 years before. Such RP and PR intervals in capture beats were invariable.
      These suggest that capture beats occurred as a result of supernormal conduction
      in the right bundle branch, which denies the possibility of ventricular
      extrasystoles. Such capture beats with the above RP and PR intervals were
      observed repeatedly.

PMID- 11320469
TI  - Candida albicans colonization of surface-sealed interim soft liners.
AB  - PURPOSE: This in-vivo investigation evaluated the effect of 2 denture sealer
      agents on the microbial colonization of a newly placed soft interim denture liner
      during a period of 14 days. MATERIALS AND METHODS: An interim soft denture liner
      (Coe-Soft; GC America, Alsip, IL) was coated with 2 different denture surface
      sealants (Palaseal [Heraeus Kulzer, Irvine, CA] and Mono-Poly [Plastodent, New
      York, NY]). Three rectangular wells of 1 cm wide x 2 cm long x 2 mm deep were
      placed in the intaglio of 10 maxillary complete dentures and filled with the soft
      liner material. The soft liner surface was treated with Palaseal (first well) and
      Mono-Poly (second well), and the unsealed (third well) was used as a control.
      These were exposed to the oral cavity for 14 days. The effect the sealant had in
      the prevention of Candidal colonization in vivo of the soft liner material was
      evaluated. Microbiological specimens were recovered from all samples and
      cultivated. Microbiological data from the control and 2-test samples in each
      denture were tabulated, and statistical analyses were performed. RESULTS: This
      investigation showed clear differences (p <.001) between the sealed and unsealed
      soft liners. The sealed material showed significantly less colonization by yeast
      and bacteria. Intercomparison of the surface denture sealers, Palaseal versus
      Mono-Poly, showed no statistically significant differences (p < .005) in total
      yeast or bacterial colonization. CONCLUSION: Coating of Coe-Soft denture liner
      with either Palaseal or Mono-Poly significantly decreased yeast and bacterial
      colonization. .

PMID- 11320470
TI  - Periodic evaluation of the occlusal vertical dimension of maxillary dentures from
      the wax trial denture through 48 hours after polymerization.
AB  - PURPOSE: This study measured the effects of commercial resin type on maxillary
      complete dentures with monoplane teeth by periodically comparing the occlusal
      vertical dimension of the polymerized dentures with the baseline, wax trial
      denture fiducial measurements. MATERIALS AND METHODS: Commercially available
      compression-molded, injection-molded, and fluid poly(methyl methacrylate) resins,
      as well as one compression-molded methyl acrylate ester copolymer, were
      evaluated. Ten dentures were fabricated from each resin using monoplane teeth.
      The occlusal vertical dimension at the articulator pin was measured at the wax
      denture stage for each specimen, and changes in occlusal vertical dimension for
      each denture were evaluated at a simulated laboratory remount, and at 0, 3, 6,
      24, and 48 hours after a simulated clinical remount. Repeated measures analysis
      of variance (alpha = 0.05) and post hoc one-way factorial analysis of variance
      and Scheffe's F-Tests for each resin group were performed using ranks of raw
      data. RESULTS: Changes in the maxillary denture mean occlusal vertical dimensions
      were recognized throughout the evaluation periods compared with the wax-denture
      baseline, and time was a significant influence on displacement (p = .0001). Only
      the compression-molded poly(methyl methacrylate) dentures exhibited a mean
      laboratory remount occlusal vertical dimension that was significantly greater
      than the mean wax denture measurement, and all resin systems exhibited occlusal
      error that was significantly less than the laboratory remount measurements at 48
      hours. At 48 hours, all resin groups exhibited mean occlusal vertical dimension
      changes that were less than 1 mm compared with the wax denture. Only compression
      molded poly(methyl methacrylate) dentures exhibited a mean 48-hour clinical
      remount measurement that was statistically similar to the mean wax denture
      occlusal vertical dimension. CONCLUSIONS: Individual maxillary dentures from all
      resin types and at all intervals exhibited dimensional change. At the last
      evaluation period, the compression-molded poly(methyl methacrylate) showed no
      change in mean occlusal vertical dimension from baseline, whereas remaining
      groups exhibited occlusal vertical dimensions significantly less than baseline.

PMID- 11320471
TI  - Tensile bond strength of resin-modified glass-ionomer cement to microabraded and
      silica-coated or tin-plated high noble ceramic alloy.
AB  - PURPOSE: The purpose of this study was to evaluate the influence of alloy surface
      microabrasion, silica coating, or microabrasion plus tin plating on the tensile
      bond strengths between a resin-modified glass-ionomer luting cement and a high
      noble alloy. Bond strength between the microabraded alloy specimens and
      conventional glass-ionomer cement or resin cement were included for comparison.
      MATERIALS AND METHODS: One hundred twenty uniform size, disk-shaped specimens
      were cast in a noble metal alloy and divided into 6 groups (n = 10 pairs/group).
      The metal surfaces of the specimens in each group were treated and cemented as
      follows. Group 1: No surface treatment (as cast, control), cemented with a resin
      modified glass-ionomer cement. Group 2: Microabrasion with 50-microm aluminum
      oxide particles, resin-modified glass-ionomer cement. Group 3: A laboratory
      microabrasion and silica coating system, resin-modified glass-ionomer cement.
      Group 4: Microabrasion and tin-plating, resin-modified glass-ionomer cement.
      Group 5: Microabrasion only, conventional glass-ionomer cement. Group 6:
      Microabrasion and tin-plating, conventional resin cement. The uniaxial tensile
      bond strength for each specimen pair was determined using an Instron Universal
      Testing Machine (Instron Corp, Canton, MA). Results were analyzed using a one-way
      analysis of variance (alpha = 0.05) and a Tukey post-hoc analysis. RESULTS: Mean
      bond strength: Group 1: 3.6 (+/- 1.5) MPa. Group 2: 4.2 (+/-0.5) MPa. Group 3:
      6.7 (+/- 0.9) MPa. Group 4: 10.6 (+/- 1.8) MPa. Group 5: 1.1 (+/- 0.4) MPa. Group
      6: 14.6 (+/- 2.3) MPa. Group 6 was significantly stronger than Group 4. The bond
      strength of specimens cemented with the resin-modified glass-ionomer cement using
      microabrasion and tin-plating (Group 4) was significantly stronger than all other
      groups except the resin cement with microabrasion and tin-plating (Group 6).
      CONCLUSION: Microabraded and tin-plated alloy specimens luted with the resin
      modified glass-ionomer cement resulted in the greatest mean tensile strengths for
      the resin-modified glass-ionomer cement groups. This strength was 73% of the mean
      tensile strength of microabraded specimens luted with resin cement.

PMID- 11320472
TI  - Predictions of cement microfracture under crowns using 3D-FEA.
AB  - PURPOSE: The objective of this research study was to test the effects of (1)
      crown margin type, (2) cement type, (3) cement thickness, (4) loading direction,
      and (5) loading magnitude on stress levels and distributions within luting cement
      that might lead to cement microfracture using three-dimensional Finite Element
      Analysis techniques. MATERIALS AND METHODS: Thirty-two three-dimensional computer
      models, as well as models for standards, were generated for a mandibular first
      premolar. Crown preparations exhibited shoulder or chamfer margin configurations,
      and zinc phosphate, zinc polycarboxylate, glass ionomer, and resin cements were
      used in thicknesses of 25 or 100 microm. Modeled crowns were loaded axially or
      obliquely at 10 and 100 MPa. Areas and levels of stress concentrations within the
      cement were determined. RESULTS: Stresses in the cement were low for all
      situations except 100 MPa oblique stressing. Stresses at the margins of crowns
      with chamfer marginal configuration were higher than those with shoulder margins.
      Stresses under oblique stressing were 10 to 150 times higher than under axial
      stressing. Except for Zn phosphate cement, cement thickness minimally affected
      stress levels and distributions. Greater stresses were found in cements with the
      greater Young's modulus. CONCLUSIONS: Although the chamfer margin design could
      lead to greater stresses near the margins that places the cement at risk for
      microfracture and possible crown failure, glass-ionomer and composite resin
      cements have more favorable mechanical properties for resisting microfracture.

PMID- 11320473
TI  - The ocular impression: A review of the literature and presentation of an
      alternate technique.
AB  - Improved fit is one advantage of a custom ocular prosthesis. Numerous methods
      exist to gain intimate tissue adaptation. This article reviews the literature
      concerning such methods and presents an improved technique for fabrication of a
      custom ocular impression tray.

PMID- 11320474
TI  - The history of articulators: early attempts to reproduce mandibular movement,
      Part III: searching for the solution to a puzzle.

PMID- 11320476
TI  - Reinventing the prosthodontic workplace.

PMID- 11320477
TI  - Strategies for laparoscopic diagnosis of malignancy.
AB  - Accurate cancer diagnosis and staging are crucial to the determination of an
      efficacious treatment plan for localized and advanced malignancy. The physician
      must differentiate patients with potentially resectable, localized disease from
      those with advanced and/or distant disease. The diagnostic and staging modalities
      currently available are expensive and often inaccurate. This can result in the
      nonoperative management of potentially resectable malignancies or, more commonly,
      in an underestimation of the preoperative cancer stage with intraoperative
      evidence of advanced/metastatic disease. The combination of laparoscopy and
      laparoscopic ultrasonography can be used to help diagnose and stage malignancies
      and select patients for either curative or palliative procedures.

PMID- 11320478
TI  - The use of laparoscopic ultrasonography in staging abdominal malignancy.
AB  - The merit of intraoperative ultrasonography in abdominal surgery has been
      recognized for several decades and has been well documented in the literature.
      With the proliferation of laparoscopic abdominal surgery, laparoscopic
      ultrasonographic technology rapidly developed and studies have confirmed its
      value in staging intra-abdominal malignancy. The combination of diagnostic
      laparoscopy and laparoscopic ultrasonography has been shown to be consistently
      superior to other preoperative imaging modalities in the staging of abdominal
      malignancy. Consequently there has been an improvement in the management of
      patients with abdominal malignancy, demonstrated by reductions in nontherapeutic
      laparotomies, improved resectability rates, and optimization of palliation.

PMID- 11320479
TI  - New imaging strategies for laparoscopic management of cancer.
AB  - The Information Age has brought to the medical and surgical community the tools
      of digital imaging and 3-dimensional (3-D) visualization. These tools provide new
      methods for diagnosis and treatment of cancer. Using 3-D reconstructions from
      computed tomography and magnetic resonance imaging scans of patient-specific
      anatomy, diagnosis from virtual endoscopy is supplementing or replacing invasive
      endoscopic procedures. These same images can be used for preoperative planning of
      complicated procedures. At the time of surgery, data fusion of the real-time
      video image and the preoperative digital image provides intraoperative
      stereotactic navigation. These augmentations can be used in many types of
      procedures, from open and minimally invasive surgery to catheter-based and energy
      directed therapies. This is a US government work. There are no restrictions on
      its use.

PMID- 11320480
TI  - Laparoscopic splenectomy for malignant diseases.
AB  - A variety of malignant diseases involving the spleen, both primary and
      metastatic, may require splenectomy for diagnosis or therapeutic reasons. The
      role of minimally invasive surgery in the management of malignant diseases
      involving the spleen is not well defined because of a lack of reported experience
      with laparoscopic splenectomy in this group. A reluctance to perform laparoscopic
      splenectomy in these patients may be explained by the technical and oncological
      challenges that often accompany malignant splenic diseases such as splenomegaly,
      perisplenitis, hilar lymphadenopathy, and fear of splenic disruption and tumor
      spillage. In our experience, the adoption of a lateral technique and the use of
      hand-assisted devices has allowed for the successful completion of laparoscopic
      splenectomy for malignant hematologic diseases including spleens up to 28 cm in
      length and greater than 3 kg morcellated weight. Laparoscopic splenectomy
      reliably alleviates the symptoms related to splenomegaly and reverses the
      hematologic abnormalities of hypersplenism. Although laparoscopic splenectomy for
      malignant diseases is feasible, the role of minimally invasive surgery in the
      staging of Hodgkin's lymphoma remains undetermined.

PMID- 11320481
TI  - Laparoscopic colectomy for malignancy.
AB  - It is clear from published series that laparoscopic colectomy for cancer can be
      performed safely by experienced surgeons, but there is a considerable learning
      curve for the procedure. Although surgeons have shown that an equivalent
      resection can be performed, it is not clear yet that this translates into
      equivalent recurrence and survival rates. Most of the expected benefits of
      minimal access surgery are being provided by laparoscopic colectomy, although
      these benefits have not been as readily achievable as those seen with other
      procedures. Even the early results of laparoscopic colectomy for cancer are
      encouraging, although the fate of this procedure rests with the long-term
      analysis of a number of trials currently underway. Laparoscopic techniques are
      continuing to evolve and improve secondary not only to technological
      breakthroughs but also advances in basic science and clinical research. This
      article provides technical descriptions to illustrate key concepts in
      laparoscopic resection of the right colon and rectosigmoid for cancer and reviews
      the results of recent prospective randomized trials.

PMID- 11320482
TI  - Minimally invasive management of hepatic metastases.
AB  - The introduction of laparoscopy for diagnosis of abdominal tumors has also
      allowed for the destruction of hepatic metastases by cryotherapy and
      radiofrequency ablation. The advantage of laparoscopically based therapy over the
      percutaneous treatment is the benefit of finding additional lesions that
      preoperative studies may not have detected. The results from available data in
      patients with metastatic colorectal carcinoma suggest an improvement in survival.
      Tumor ablation in patients offers an 18- to 36-month median survival and the
      possibility of 50% and 24% survival rates at 2 and 5 years, respectively.
      Patients with metastases from melanoma, breast, esophagus, lung, stomach,
      pancreas, and gynecologic malignancies have historically not demonstrated
      improved survival after hepatic resection. The value of hepatic tumor ablation
      for metastases from these lesions remains undetermined.

PMID- 11320483
TI  - Laparoscopic interventions in lymphoma management.
AB  - The widespread use of laparoscopy has been made possible by the exponential
      improvements in imaging technology as well as the development of specialized
      instruments. Although the use of laparoscopy for procedures such as
      cholecystectomy has become commonplace, its applicability in the management of
      malignancies remains in evolution. The role of the surgeon in the care of the
      patient with lymphoma is limited mostly to obtaining a diagnosis. Laparoscopy can
      play a significant role in the care of the patient requiring accurate intra
      abdominal staging. The staging procedure is conducted in a fashion identical to
      the open procedure, including multiple liver biopsies, a splenectomy, and
      multiple lymph node biopsies. Patients with non-Hodgkin's lymphoma almost never
      require staging, and laparoscopy may play a role in obtaining tissue for
      diagnosis in a small fraction of patients. Patients with Hodgkin's disease who
      have diffuse disease (stages III and IV) never need staging because they will all
      receive chemotherapy. Likewise, patients with limited disease (stage I) are
      usually treated with radiation therapy alone. Some patients with stage II disease
      will require surgical staging, which should be performed laparoscopically. The
      laparoscopic approach to this procedure may afford benefits to the patient
      including decreased hospitalization, morbidity, and reduced delays in obtaining
      definitive treatment.

PMID- 11320484
TI  - Laparoscopic placement of a continuous hepatic artery infusion pump.
AB  - Regional liver infusion chemotherapy has been used for several decades in the
      treatment of isolated hepatic metastases from colorectal cancer. Although
      implantation of infusion pumps has traditionally required a laparotomy, minimally
      invasive techniques have been used recently in an attempt to reduce the morbidity
      resulting from pump placement. This report describes a technique for laparoscopic
      pump placement and presents the investigators' results with this technique.

PMID- 11320485
TI  - Control of interstitial fluid pressure: role of beta1-integrins.
AB  - This review has summarized experiments which show that the connective tissue
      cells can actively modulate the physical properties of the interstitial matrix so
      that it becomes an "active" participant in transcapillary fluid exchange and
      thereby interstitial fluid homeostasis. The beta1-integrin system seems to
      provide a common pathway by which the cells can both raise and lower the
      interstitial fluid pressure. The experiments with alpha-trinositol and platelet
      derived growth factor-BB suggest that the connective tissue can serve as a novel
      target for pharmacologic intervention in inflammation.

PMID- 11320486
TI  - Physiology and pathophysiology of renal aquaporins.
AB  - The discovery of aquaporin-1 (AQP1) by Agre and associates answered the
      longstanding biophysical question of how water specifically crosses biological
      membranes. In the kidney at least 7 aquaporins are expressed at distinct sites.
      AQP1 is extremely abundant in the proximal tubule and descending thin limb and is
      essential for urinary concentration. AQP2 is exclusively expressed in the
      principal cells of the connecting tubule and collecting duct and is the
      predominant vasopressin-regulated water channel. AQP3 and AQP4 are both present
      in the basolateral plasma membrane of collecting duct principal cells and
      represent exit pathways for water reabsorbed apically via AQP2. Studies in
      patients and transgenic mice have shown that both AQP2 and AQP3 are essential for
      urinary concentration. Three additional aquaporins are present in the kidney.
      AQP6 is present in intracellular vesicles in collecting duct intercalated cells
      and AQP8 are present intracellularly at low abundance in proximal tubules and
      collecting duct principal cells but the physiological function of these 2
      channels remain undefined. AQP7 is abundant in the brush border of proximal
      tubule cells and is likely to be involved in proximal tubule water reabsorption.
      A series of studies have underscored crucial roles of aquaporins for regulation
      of renal water metabolism and hence body water balance. Moreover it has become
      clear that dysregulation of aquaporins, and especially AQP2 is critically
      involved in many water balance disorders. Lack of functional AQP2 is seen in
      primary forms of diabetes insipidus, and reduced expression and targeting is seen
      in several diseases associated with urinary concentrating defects such as
      acquired nephrogenic diabetes insipidus, postobstructive polyuria, as well as
      acute and chronic renal failure. In contrast, in conditions with water retention
      such as severe congestive heart failure, pregnancy and SIADH both AQP2 expression
      levels and apical plasma membrane targetting is increased suggesting a role for
      AQP2 in the development of water retention. Continued analysis of the aquaporins
      is providing detailed molecular insight into the fundamental physiology and
      pathophysiology of water balance and water balance disorders.

PMID- 11320487
TI  - Involvement of the renal natriuretic peptide urodilatin in body fluid regulation.
AB  - Urodilatin, a 32-aminoacid peptide, is expressed in distal tubular cells of the
      human kidney and presumably released into the luminal part of the nephron to
      exert its effect via activation of membrane-bound guanylyl cyclases (type A) at
      the medullary collecting duct. Thereby, the tubular reabsorption of sodium is
      inhibited and natriuresis is stimulated. The peptide is derived from the same
      gene and propeptide as the atrial natriuretic peptide (ANP), a more N-terminal
      cleavage in the human kidney than in other body tissues may be responsible for
      the existence of this renal natriuretic peptide and its increased stability in
      the extreme environment of the kidney and primary urine. The results of a
      sequence of human and animal physiology experiments has suggested that the renal
      natriuretic peptide, rather than its cardiac analog ANP, may play an essential
      role in mediating urinary sodium excretion. First observations are made
      suggesting a contribution of the renal natriuretic peptide also to disturbed
      sodium handling under pathophysiological conditions.

PMID- 11320488
TI  - Hormonal insights into the pathogenesis of cyclic idiopathic edema.
AB  - Cyclic idiopathic edema is a nonlife-threatening syndrome of excessive weight
      gain. Although the cause is not clear, a number of hormones are postulated to be
      involved. Altered vascular permeability and increased lymph formation may also be
      part of the disorder. This article reviews some relevant data as to the
      pathogenesis of this noninflammatory disorder, concluding with an approach to
      diagnosis and therapy.

PMID- 11320489
TI  - Edema and acute renal failure.
AB  - Acute renal failure (ARF) with overhydration and edematous state may follow Acute
      endocapillary proliferative glomerulonephritis and extracapillary
      glomerulonephritis, because of reduction of the glomerular capillary area
      available for filtration. But ARF may also be observed in edematous patients with
      minimal change nephrotic syndrome; it may require dialysis until recovery and is
      attributable to some of the following factors: (1) ischemic renal injury, (2)
      hypovolemia, (3) interstitial edema with tubular collapse, (4) redistribution of
      renal blood flow (RBF) from cortical to juxtaglomerular nephrons, (5) decrease of
      capillary filtration coefficient (Kf), (6) use of nonsteroidal antiinflammatory
      drugs. Congestive heart failure also leads to prerenal azotemia and edema
      formation secondary to salt retention. Multiple organ dysfunction syndrome (MODS)
      is frequently associated with ARF; but edema occurs even without ARF in septic
      patients with severe inflammatory response syndrome (SIRS). ARF may follow severe
      burns; burned patients are frequently edematous because of a rapid leak of fluid
      from the vascular bed into the wound; edema in undamaged areas occurs in the
      'flow phase', because of a fall of oncotic pressure because of massive loss of
      plasma proteins into the wound. Edema must be treated with diuretics or by
      dialysis.

PMID- 11320490
TI  - Nephritic edema.
AB  - Nephritic edema results from the primary retention of salt. Acute
      glomerulonephritis is the prototypical form of the disorder. The stimulus for the
      salt retention arises within the kidney by an unknown mechanism. As effective
      arterial blood volume (EABV) was normal at the start of the disease process, it
      becomes expanded as salt and water are added to it. The pathophysiological
      sequelae of this process are compared with those which follow the salt retention
      of congestive heart failure (CHF). The latter is a syndrome in which salt
      retention is secondary, driven by the contraction of EABV which is at the heart
      of CHF. Finally, mechanisms responsible for the salt retention of nephrosis are
      considered. It is possible, and even likely, that most patients with nephrotic
      edema have primary salt retention, rather than secondary edema. If this view is
      correct, salt is retained not because of urinary protein loss and its consequent
      hypoalbuminemia, but rather because of the glomerulopathy which caused the
      syndrome in the first place.

PMID- 11320491
TI  - Nephrotic edema.
AB  - This article starts with a concise synopsis of the history of edema. The role of
      underfilling, overflow, antidiuretic hormone, and acquaporins is subsequently
      discussed. Emphasis is given to the use of diuretics in edematous patients. The
      role and risks of albumin infusion are illustrated. The new hypothesis of pulse
      reverse osmosis is discussed. The final section deals with the measurement of
      colloid osmotic pressure in the clinical setting.

PMID- 11320492
TI  - Correction of hyponatremia.
AB  - The development of selective oral V2 receptor antagonists has led to confirmation
      of established concepts of the pathogenesis of hyponatremia and to new approaches
      to its treatment. V2 receptor antagonists are effective and promising agents.
      Their properties as specific pharmacologic tools will facilitate the treatment of
      the different types of hyponatremia because of the improved predictability of
      response, and improved control of fine tuning of responses, compared with what is
      achieved by current therapies. In addition, the quality of life of hyponatremic
      patients will improve because there will be less need for severe fluid
      restrictions. It is likely that these agents can be administered over prolonged
      periods of time.

PMID- 11320493
TI  - Pathogenesis of heart failure.
AB  - Heart failure is a complex clinical syndrome, and only part of this syndrome is
      based on the mechanical failure of the heart muscle itself to provide sufficient
      systemic perfusion. Heart failure is accompanied by the activation of various
      immunologic and neurohumoral mechanisms. These may be intended by nature to be
      physiologically beneficial, but eventually become deleterious as they provoke
      ischemic, proarrhythmic, vascular, and structural changes in the myocardium that
      contribute to the versatile symptoms of the heart failure syndrome. Today's
      concept of the pathogenesis of heart failure regards heart failure as a dynamic
      state influenced by at least 2 major mechanisms, namely "neurohumoral" activation
      and ventricular remodeling. Progressive chronic heart failure can be viewed as a
      result of the prolonged impact of both pathogenetic mechanisms. This article will
      describe briefly the features of the neurohumoral forces on the pathogenesis of
      heart failure, including immunologic forces, which also influence the remodeling
      process.

PMID- 11320494
TI  - Hemodialitic treatment of cardiac failure.
AB  - The various options for treatment of diuretic-resistant edema in heart failure
      and report on their experience with on line bicarbonate daily hemofiltration (135
      min) in 16 patients with congestive heart failure IV class NYHA is discussed. The
      outcome was excellent. Only 6 patients died. Survival averaged 25 weeks in 4
      patients. A total of 6 patients are still alive on dialysis after 18 to 52 weeks.

PMID- 11320495
TI  - Bioelectrical impedance analysis in heart transplantation: early and late
      changes.
AB  - The objectives of this study were to perform bioelectrical impedance analysis
      before and after heart transplantation with comparison to healthy subjects. Eight
      patients (7 men, 1 woman) before (day 0) and after transplantation (day 3, 7, 12,
      15, and 180) and 24 healthy controls, matched for sex, age, and body mass were
      studied. Data collection included bioelectrical impedance analysis (resistance,
      reactance, and estimates of body water), clinical, and laboratory measurements.
      Compared with controls, patients had at baseline significantly higher reactance,
      not significantly different resistance, body weight, total body water, and intra-
      to extracellular water ratio. After surgery, for reactance, there was an acute
      decrease followed by a slow, progressive increase up to normal level by day 15.
      Resistance and body weight did not significantly change; the intra- to
      extracellular water ratio significantly decreased with stable total body water.
      Changes in reactance are the main effects induced on bioelectrical impedance by
      heart transplantation. Acutely, there is a large decrease which likely reflects
      changes both in water distribution and in cell membrane function. The late
      changes more likely reflect the shift of body water from the extra- to the
      intracellular space with stable total body water.

PMID- 11320496
TI  - Dry weight in hemodialysis: volemic control.
AB  - In dialysis patients the chronic fluid overload may represent a nonphysiologic
      condition which brings both arterial hypertension and hemodynamic instability.
      Volume expansion is significantly correlated to casual predialysis blood pressure
      and 24-hour arterial pressure. The normalization of the patient hydration status
      is not only followed by a reduction in pressure values but also by an improvement
      of the circadian blood pressure rhythm. On the other hand, hypovolemia and
      underhydration combined with an impaired cardiovascular regulatory response may
      generate the dialysis-related hypotension. Many techniques have been introduced
      to obtain an objective measurement of the hydration status: postdialysis
      radiological chest examination, plasma atrial natriuretic peptide (ANP), and
      plasma cyclic guanidine monophosphate (cGMP) levels, multifrequency electrical
      bioimpedance and the continuous plasma volume measurement. The latter, alone or
      in combination with provocative tests (stop and go of the ultrafiltration), may
      help in optimizing plasma volume contraction. The plasma volume monitoring avoids
      the risk of hypovolemic hypotension and facilitates the achievement of a correct
      dry body weight. The biofeedback system, exploiting the automatic control of the
      intradialytic variations, may represent an additional advantage in the
      formulation of an ideal postdialysis blood volume that overlaps the patient's dry
      weight.

PMID- 11320497
TI  - Dry weight and sodium balance.
AB  - To achieve good blood pressure control and minimal intradialytic patient
      discomfort, it is very important to define the correct dry weight and
      individualize the "adequate" dialysate sodium concentration. Given the highly
      variable amounts of sodium introduced during interdialytic periods, the use of
      the sodium and conductivity kinetic models guarantees adequate sodium removal in
      each patient with each treatment. According to our data, the imprecision of the
      sodium kinetic model was less than 0.84 mEq/L; that of the conductivity kinetic
      model, which has the advantage not requiring blood or dialysate samples, was less
      than 0.14 mS/cm. In paired filtration dialysis (PFD), the corresponding figures
      were less than 1.1 mEq/L and less than 0.1 mS/cm. A multicenter prospective,
      controlled and randomized trial has demonstrated that the application of the
      conductivity kinetic model in PFD makes it possible to improve cardiovascular
      stability in patients prone to dialysis hypotension. The sodium kinetic model is
      difficult to apply in routine clinical practice because of the need for blood and
      dialysate samples, but this may be overcome by the conductivity kinetic model,
      which is a very promising tool for achieving a zero intradialytic sodium balance
      and improving cardiovascular stability.

PMID- 11320498
TI  - Adsorption of natriuretic factors in uremia.
AB  - Patients with end-stage renal disease have a deranged sodium and water
      homeostasis leading to chronic volume overload. Atrial natriuretic peptides
      (ANPs) are circulating hormones that are involved in the regulation of volume
      homeostasis, blood pressure control, and electrolyte balance. In hemodialysis
      patients plasma ANPs are highly elevated and decrease during the dialysis session
      when fluid is removed. However, hemodialysis treatment never corrects the defect
      in the metabolism of these peptides and their circulating concentrations do not
      return to levels found in healthy controls. Besides uremia and chronic volume
      overload, other factors such as cardiac dysfunction or hypertension may
      contribute to the elevated plasma concentrations of ANPs. ProANP fragments which
      derive from the N-terminus of the ANP prohormone have been also found in the
      circulation and they have biological functions similar to alpha-ANP (ie, the C
      terminus of the prohormone). The proANP peptides proANP(1-30), proANP(31-67), and
      proANP(1-98) are increased in patients undergoing regular hemodialysis treatment,
      but their decrease during the dialysis procedure is less pronounced than for
      alpha-ANP or cyclic GMP. Cellulose triacetate dialyzer membrane material lowered
      the plasma concentrations of proANP(1-30), proANP(31-67), and proANP(1-98)
      significantly more than polysulfone, whereas alpha-ANP and cyclic GMP were not
      differently affected. Aside from a variety of factors that influence circulating
      natriuretic factors in the uremic patient, there is evidence for differences in
      dialyzer membrane adsorption of these peptides which speculatively may be linked
      to dialysis-associated symptoms.

PMID- 11320499
TI  - Cerebral edema.
AB  - Two major types of brain edema may be discriminated, characterized by intra- or
      extracellular fluid accumulation. Intracellular (cytotoxic) edema is found after
      cerebral ischemia, trauma, intoxications, and metabolic disorders. Pathogenetic
      mechanisms include (1) failure of active Na+ export via Na/K-ATPase because of
      energy shortage, (2) increased Na+-permeability, or (3) activation of Na+-driven
      membrane pumps. The latter mechanism reflects homeostatic functions of astroglia,
      which at reduced availability of energy resources uses the remaining Na+-gradient
      to fuel uptake of transmitters such as glutamate, and for control of pH(i).
      Extracellular (vasogenic) edema is caused by damage to the blood-brain barrier
      and consists of protein-rich fluid. It accompanies brain tumors, trauma,
      infections, and hypertensive crisis. Pathogenetic mechanisms include (1) opening
      of tight junctions responsible for barrier opening in acute conditions, or (2)
      sprouting of immature blood vessels in chronic conditions such as brain tumors.

PMID- 11320500
TI  - Pathogenesis and treatment of fluid and electrolyte imbalance in cirrhosis.
AB  - Patients with cirrhosis have significant abnormalities in their fluid and
      electrolyte balance, this is manifested mainly by the development of ascites and
      edema. Ascites is the most common complication of patients with cirrhosis and its
      development constitutes the first and most important manifestation of the
      disease. Patients with advanced cirrhosis and portal hypertension often show an
      abnormal extracellular fluid volume regulation, which results in accumulation of
      fluid as ascites, pleural effusion, or edema. This abnormality in volume
      regulation is associated with significant changes in the splanchnic circulation
      and renal circulation that induce sodium and water retention. During the last
      decade significant advances have been accomplished in regard to the pathogenesis
      and the treatment ascites. The description of a new hypothesis, the
      identification of new vasoactive factors involved in the pathogenesis of arterial
      vasodilation and the introduction of different therapeutic modalities such as
      therapeutic paracentesis, transjugular intrahepatic portosystemic shunt,
      aquaretics agents, and liver transplantation are all proof of this. Likewise, the
      description of predictive factors for the survival of patients with cirrhosis has
      been of major importance for the identification of patients candidates for liver
      transplantation.

PMID- 11320502
TI  - Renal tubular function by lithium clearance in liver cirrhosis.
AB  - Increased tubule sodium reabsorption has been largely suspected in liver
      cirrhosis (LC), however studies in humans have produced contrasting results.
      Therefore to ascertain the entity of renal sodium handling in LC this study was
      devised. A total of 13 patients with child A LC were studied along with 26 age
      sex matched healthy controls (HC). Patients and controls were kept on daily Na
      intake of 100 mmol for at last 1 week, by measuring glomerular filtration rate
      (GFR; inulin) and lithium clearance. We have calculated (1) C(Li); (2) the
      absolute reabsorption of isotonic fluid in the proximal tubule (APR) as GFR -
      C(LI); (3) the fractional proximal sodium reabsorption (FPRNa) as 1 -
      (C(Li)/GFR); (4) the absolute distal reabsorption of sodium (ADRNa) as (C(LI) -
      C(Na)) x P(Na;) and (5) the fractional distal sodium reabsorption (FDRNa) as
      (C(LI) - C(Na))/C(Li). GFR was significantly lower in LC (P<.001), C(Li) was
      significantly higher in LC than in HC (P<.001). APRNa and FPRNa were reduced in
      LC (P<.0001). ADRNa was higher in LC than in HC (P<.001). No difference was found
      for FDRNa. In conclusion, lithium clearance discloses an increase sodium
      reabsorption in distal tubule in humans with LC.

PMID- 11320501
TI  - Sodium retention in preascitic stage of cirrhosis.
AB  - Renal Na+ handling abnormalities have been shown in preascitic cirrhosis. To
      investigate the underlying pathophysiology, the effects of different sodium
      intakes on Na(+) balance and renal hemodynamics were assessed at 100 mEq Na+/day
      (low-sodium diet [LSD]) and after 6 days of 250 mEq Na+/day (high-sodium diet
      [HSD]). Eight asymptomatic patients with cirrhosis (Pugh-Child A class) (PAC) and
      10 healthy controls (CON) were studied. At HSD, although CON readjusted Na+
      excretion within the fourth day, PAC did not reach the new balance and developed
      a final greater Na+ retention (+437 mEq in PAC v +228 mEq in CON, P<.001). In
      PAC, fractional Na+ excretion (FENa) was significantly lower than in CON at LSD
      (P<.05), and, after HSD, increased in both groups (P<.05). In PAC, renal vascular
      resistances (RVR) at LSD resulted lower than in CON (P<.05) and failed to
      decrease after HSD. As a consequence, after HSD, glomerular filtration rate and
      renal plasma flow failed to increase in PAC. PRA and plasma aldosterone were
      significantly lower in PAC, than in CON at LSD (P<.05), and decreased in both
      groups after HSD (P<.05). Proximal Na+ reabsorption (RProx) [as indicated by
      fractional free water clearance measured in a state of maximal water diuresis] at
      LSD was lower in PAC than in CON (P<.05) and decreased in both groups after HSD
      (P<.05). In summary, early stages of cirrhosis are characterized by: (1) a
      reduction of RVR, probably associated with splanchnic vasodilation; (2) a Na+
      retention already at LSD, as indicated by the lower FENa observed in PAC, that
      produces extracellular volume (ECV) expansion, with a consequent RProx and renin
      angiotensin-aldosterone axis (RAS) suppression; (3) a greater Na+ retention after
      HSD, associated with an abnormal adaptation of renal hemodynamic, a greater ECV
      expansion and a consequent Rprox and RAS suppression. These data show the
      presence of early renal hemodynamic dysfunction in PAC. Our findings also show in
      this phase of the disease a preserved adaptation of RProx and RAS, thus
      suggesting that the observed tubular Na+ reabsorption derangement is probably
      related to abnormal ANP behavior.

PMID- 11320503
TI  - Stable sol-gel microstructured and microfluidic networks for protein patterning.
AB  - We demonstrate the formation of micropatterned sol-gel structures containing
      active proteins by patterning with polydimethylsiloxane (PDMS) microchannels. To
      transport sol solution efficiently into the hydrophobic PDMS microchannels, a
      hydrophilic-hydrophobic block copolymer was used to impart hydrophilicity to the
      PDMS microchannels. Poor adhesion of the micropatterned gel structure onto glass
      slides was improved by treating the glass surface with a polymeric substrate. To
      minimize cracks in the gel microstructure, hybrid matrices of interpenetrating
      organic and inorganic networks were prepared containing the reactive organic
      moieties polyvinylalcohol or polyvinylpyrrolidone. Retention of biochemical
      activity within the micropatterned gel was demonstrated by performing
      immunobinding assays with immobilized immunoglobulin G (IgG) antibody. The
      potential application of microfluidics technology to immobilized-enzyme
      biocatalysis was demonstrated using PDMS-patterned microchannels filled with
      trypsin-containing sol-gels. This work provides a foundation for the
      microfabrication of functional protein chips using sol-gel processes.

PMID- 11320504
TI  - Characterization of monoclonal antibody fragments produced by plant cells.
AB  - Production of a murine IgG1 was investigated using hairy roots, shooty teratomas,
      and suspended cells of transgenic tobacco. In all cases, in addition to complete
      assembled antibody, two to four major antibody fragments accumulated in the
      biomass. A range of protease inhibitors, protein-stabilizing agents, inhibitors
      of N-glycosylation and protein secretion, glycan-reactive agents, and affinity
      probes was used to characterize these fragments and investigate their sites and
      mechanisms of formation. The fragments were not experimental artifacts caused by
      antibody degradation during tissue homogenization and sample preparation, nor did
      they represent glycosylation variants. All of the molecules were actively
      secreted into the culture media and some showed evidence of Golgi-associated
      glycan processing, indicating they were not assembly intermediates. Antibody
      fragments of 50 and 80 kDa were identified mainly as the products of
      extracellular degradation in the root and shoot apoplast; the 80-kDa fragment was
      also present in cell suspension medium, and in suspended cell biomass toward the
      end of the growth phase. Larger 120- and 135-kDa fragments were most likely
      produced by proteolytic degradation along the secretory pathway outside of the
      endoplasmic reticulum (ER) and Golgi apparatus; the carbohydrate residues of the
      135-kDa antibody suggest formation between these organelles. Inhibition of
      protein secretion and retention of antibody in the ER and/or Golgi reduced
      fragmentation and increased antibody accumulation levels, probably by reducing
      exposure to the principal sites of protease activity. This work highlights the
      importance of foreign protein degradation in plant tissues as a mechanism for
      posttranslational product loss. Identifying the nature of these degradative
      processes is a first step toward alleviating their effects, improving protein
      yields, and enhancing the feasibility of plants as a commercial means for large
      scale protein production.

PMID- 11320505
TI  - Determination of the maximum specific uptake capacities for glucose and oxygen in
      glucose-limited fed-batch cultivations of Escherichia coli.
AB  - A simple pulse-based method for the determination of the maximum uptake
      capacities for glucose and oxygen in glucose limited cultivations of E. coli is
      presented. The method does not depend on the time-consuming analysis of glucose
      or acetate, and therefore can be used to control the feed rate in glucose limited
      cultivations, such as fed-batch processes. The application of this method in fed
      batch processes of E. coli showed that the uptake capacity for neither glucose
      nor oxygen is a constant parameter, as often is assumed in fed-batch models. The
      glucose uptake capacity decreased significantly when the specific growth rate
      decreased below 0.15 h(-1) and fell to about 0.6 mmol g(-1) h(-1) (mmol per g
      cell dry weight and hour) at the end of fed-batch fermentations, where specific
      growth rate was approximately 0.02 h(-1). The oxygen uptake capacity started to
      decrease somewhat earlier when specific growth rate declined below 0.25 h(-1) and
      was 5 mmol g(-1) h(-1) at the end of the fermentations. The behavior of both
      uptake systems is integrated in a dynamic model which allows a better fitting of
      experimental values for glucose in fed-batch processes in comparison to generally
      used unstructured kinetic models.

PMID- 11320506
TI  - Stability of crystalline proteins.
AB  - By using two model proteins, glucose oxidase and lipase, we demonstrate that dry
      crystalline formulations are significantly more stable than their amorphous
      counterparts. The results of Fourier-transform infrared spectroscopy indicate
      that crystalline proteins better maintain their native conformation in
      accelerated stability studies. The lower tendency of crystalline proteins to
      aggregate is confirmed by size-exclusion chromatography. The data suggest that
      protein crystallization may significantly improve some aspects of protein
      handling, and change the way biopharmaceuticals are produced, formulated, and
      delivered.

PMID- 11320507
TI  - Strength of mid-logarithmic and stationary phase Saccharopolyspora erythraea
      hyphae during a batch fermentation in defined nitrate-limited medium.
AB  - A method for measuring mechanical properties of Saccharopolyspora erythraea is
      reported with data from a batch fermentation. Briefly, hyphae were glued to the
      end of a tungsten filament mounted horizontally on a sensitive force transducer.
      Free ends of hyphae were trapped against a flat surface by a second probe. The
      force transducer and tungsten filament were then moved at a fixed rate, the hypha
      were strained, and the force resisting motion recorded. From these data the
      maximum force resisting motion is taken as the force at which breakage occurs.
      Hyphae from the mid-logarithmic phase of a simple batch fermentation on defined
      medium were found to have a breaking force of 890 +/- 160 nN (95% confidence),
      while stationary phase hyphae were weaker at 580 +/- 150 nN. Video recordings of
      the experiments allowed an approximation of breaking strain, which did not differ
      significantly between samples at 0.18 +/- 0.03. Electron microscopy was used to
      measure cell wall thickness, cell diameter, and hence cell wall cross-sectional
      area. The ultimate tensile strength was estimated to be 24 +/- 3 MPa with no
      difference between the two samples, the lower breaking force of the stationary
      phase hyphae being attributed to a thinner cell wall. Assuming a linear
      relationship between stress and strain, the elastic modulus was estimated to be
      140 +/- 30 MPa. These values are comparable with other structural biological
      materials such as yeast cell walls and collagen.

PMID- 11320508
TI  - Effects of oxygenation and flow on the viability and function of rat hepatocytes
      cocultured in a microchannel flat-plate bioreactor.
AB  - The goal of this study was to investigate the viability and synthetic function of
      rat hepatocytes cocultured with 3T3-J2 fibroblasts in a small-scale microchannel
      flat-plate bioreactor with and without an internal membrane oxygenator under
      flow. Bioreactor channel heights ranged between 85 and 500 microm and medium flow
      rates ranged between 0.06 and 4.18 mL/min. The results showed that the bioreactor
      without the oxygenator resulted in significantly decreased viability and function
      of hepatocytes, whereas hepatocytes in the bioreactor with internal membrane
      oxygenator were able to maintain their viability and function. The shear stress
      calculations showed that, at lower wall shear stresses (0.01 to 0.33 dyn/cm(2)),
      hepatocyte functions, measured as albumin and urea synthesis rates, were as much
      as 2.6- and 1.9-fold greater, respectively, than those at higher wall shear
      stresses (5 to 21 dyn/cm(2)). Stable albumin and urea synthesis rates for 10 days
      of perfusion were also demonstrated in the bioreactor with internal membrane
      oxygenator. These results are relevant in the design of hepatocyte bioreactors
      and the eventual scaling-up to clinical devices.

PMID- 11320509
TI  - Scale-down model to simulate spatial pH variations in large-scale bioreactors.
AB  - For the first time a laboratory-scale two-compartment system was used to
      investigate the effects of pH fluctuations consequent to large scales of
      operation on microorganisms. pH fluctuations can develop in production-scale
      fermenters as a consequence of the combined effects of poor mixing and adding
      concentrated reagents at the liquid surface for control of the bulk pH. Bacillus
      subtilis was used as a model culture since in addition to its sensitivity to
      dissolved oxygen levels, the production of the metabolites, acetoin and 2,3
      butanediol, is sensitive to pH values between 6.5 and 7.2. The scale-down model
      consisted of a stirred tank reactor (STR) and a recycle loop containing a plug
      flow reactor (PFR), with the pH in the stirred tank being maintained at 6.5 by
      addition of alkali in the loop. Different residence times in the loop simulated
      the exposure time of fluid elements to high values of pH in the vicinity of the
      addition point in large bioreactors and tracer experiments were performed to
      characterise the residence time distribution in it. Since the culture was
      sensitive to dissolved oxygen, for each experiment with pH control by adding base
      into the PFR, equivalent experiments were conducted with pH control by addition
      of base into the STR, thus ensuring that any dissolved oxygen effects were common
      to both types of experiments. The present study indicates that although biomass
      concentration remained unaffected by pH variations, product formation was
      influenced by residence times in the PFR of 60 sec or longer. These changes in
      metabolism are thought to be linked to both the sensitivity of the acetoin and
      2,3-butanediol-forming enzymes to pH and to the inducing effects of dissociated
      acetate on the acetolactate synthase enzyme.

PMID- 11320510
TI  - Fluorescent detection of cyanobacterial DNA using bacterial magnetic particles on
      a MAG-microarray.
AB  - Bacterial magnetic particles (BMPs) were used for the identification of
      cyanobacterial DNA. Genus-specific oligonucleotide probes for the detection of
      Anabaena spp., Microcystis spp., Nostoc spp., Oscillatoria spp., and
      Synechococcus spp. were designed from the variable region of the cyanobacterial
      16S rDNA of 148 strains. These oligonucleotide probes were immobilized on BMPs
      via streptavidin-biotin conjugation and employed for magnetic-capture
      hybridization against digoxigenin-labeled cyanobacterial 16S rDNA. Bacterial
      magnetic particles were magnetically concentrated, spotted in 100-microm-size
      microwell on MAG-microarray, and the fluorescent detection was performed. This
      work details the development of an automated technique for the magnetic
      isolation, the concentration of hybridized DNA, and the detection of specific
      target DNA on MAG-microarray. The entire process of hybridization and detection
      was automatically performed using a magnetic-separation robot and all five
      cyanobacterial genera were successfully discriminated.

PMID- 11320511
TI  - Integrated flow-injection processing for on-line quantification of plasmid DNA
      during cultivation of E. coli.
AB  - An integrated flow-injection processing (FIP) system for the quantification of
      plasmids during cultivation is described. The system performs on-line sampling,
      cell lysis, and quantification of plasmids in an integrated manner during
      cultivation of E. coli. The system was operated by using a miniaturized expanded
      bed column which can be used for handling samples containing cells and cell
      debris without interfering with the binding analysis. Two types of detectors (one
      measuring UV absorbance at 254 nm and a fluorometer) are used for on-line plasmid
      detection. The system was developed using standard solutions and it was
      successfully applied in monitoring plasmid contents during a cultivation of E.
      coli.

PMID- 11320512
TI  - In vivo dynamics of galactose metabolism in Saccharomyces cerevisiae: metabolic
      fluxes and metabolite levels.
AB  - The dynamics of galactose metabolism in Saccharomyces cerevisiae was studied by
      analyzing the metabolic response of the CEN.PK 113-7D wild-type strain when
      exposed to a galactose pulse during aerobic growth in a galactose-limited steady
      state cultivation at a dilution rate of 0.097 h(-1). A fast sampling technique
      and subsequent methanol-chloroform/solid phase extractions were applied for in
      vivo measurements of the dynamic changes of the AMP, ADP, ATP levels and the
      sugar phosphates of the Leloir pathway. The ATP level was found to be
      significantly lower for yeast growing under galactose limitation (0.37 +/- 0.05
      micromol/g CDW) than what has been reported for growth under glucose limitation.
      The galactose pulse of 5.58 mM was consumed within 40 min (t = 40) and 7 min
      after the pulse was added cell growth stopped. Subsequently, the cells started to
      grow and at t = 30 the specific growth rate had recovered to half the steady
      state growth rate (0.047 h(-1)). To evaluate the change in flux distribution at
      steady state and during the galactose transient, a stoichiometric model
      describing the aerobic metabolism of S. cerevisiae was set up for quantification
      of the metabolic fluxes. At t = 7 the flux entering the TCA cycle was low and
      acetate and ethanol started to be excreted to the extracellular medium. During
      recovery of cell growth the flux entering the TCA cycle increased again, and at t
      = 30 this flux exceeded the corresponding steady-state flux. During the pulse an
      enhanced level of Gal-1P was measured, which may be responsible for a toxic
      metabolic response in S. cerevisiae. The increase in the Gal-1P concentration is
      intensified by the low affinity of Gal7 towards Gal-1P and, hence, under the
      physiological conditions examined Gal7 seems to exert control over flux through
      the Leloir pathway.

PMID- 11320513
TI  - Highly efficient synthesis of ampicillin in an "aqueous solution-precipitate"
      system: repetitive addition of substrates in a semicontinuous process.
AB  - The synthesis of ampicillin catalyzed by Escherichia coli penicillin acylase was
      optimized in an aqueous system with partially dissolved antibiotic nucleus 6
      aminopenicillanic acid (6-APA). The yields of both 6-APA and acyl donor could be
      improved by repetitively adding substrates to the reaction, allowing the
      concentration of 6-APA to remain saturated throughout. In this reaction concept,
      with four subsequent additions of substrates, 97% conversion of 6-APA and 72% of
      D-(-)-phenylglycine methyl ester (D-PGM) to ampicillin was achieved. The
      synthetic potential of this concept was estimated using a mathematical model
      which showed that by increasing the amount of added substrates a nearly
      quantitative conversion of 6-APA and 85% conversion of acyl donor into ampicillin
      could be achieved.

PMID- 11320514
TI  - Hepatic colorectal metastases and extrahepatic disease.

PMID- 11320515
TI  - Relationship between excision volume, margin status, and tumor size with the
      development of local recurrence in patients with ductal carcinoma-in-situ treated
      with breast-conserving therapy.
AB  - BACKGROUND AND OBJECTIVES: We reviewed our institution's experience treating
      patients with ductal carcinoma-in-situ (DCIS) with breast-conserving therapy
      (BCT) to help define the interrelationship between excision volume, margin
      status, and tumor size with local recurrence. METHODS: From January 1980 to
      December 1993, 146 patients received BCT for DCIS. All patients underwent
      excisional biopsy and 95 cases (64%) underwent re-excision. Each patient received
      whole breast radiation to a median dose of 45 Gy. An additional 139 cases (94%)
      received a supplemental boost to the tumor bed (median total dose 60.4 Gy). The
      median follow-up is 7.2 years. RESULTS: Seventeen patients developed an
      ipsilateral breast failure for a 5- and 10-year actuarial rate of 10.2 and 12.4%,
      respectively. On multivariate analysis, patient age, margin status, the number of
      slides containing DCIS, the number of DCIS/cancerization of lobules (COL) foci
      near (< 5 mm) the margin, and a smaller volume of excision (< 60 cm(3)) were all
      independently associated with outcome. Although the local recurrence rate
      generally decreased as margin distance increased, these differences did not
      achieve statistical significance unless the volume of excision was taken into
      consideration. CONCLUSIONS: These findings suggest that the success of BCT is
      directly related to the degree of surgical removal of DCIS and that margin status
      alone may be suboptimal in defining excision adequacy.

PMID- 11320516
TI  - Is the UICC pathological node status system useful? Comparison with the Japanese
      Breast Cancer Society pathological node status system.
AB  - BACKGROUND AND OBJECTIVES: The UICC and the Japanese Breast Cancer Society have
      different TNM classifications. There is a large discrepancy between the
      pathological node status in the UICC (UICC-NS) and JBCS (JBCS-NS) systems. We
      compared the UICC-NS with the JBCS-NS. METHODS: Reviewed were data on 1,684
      invasive ductal carcinomas at the Cancer Institute Hospital from 1981 to 1986.
      Each case was categorized according to the UICC-NS and JBCS-NS, respectively.
      Overall survival 10 years after surgery (OS) by UICC-NS and JBCS-NS was
      calculated by the Kaplan-Meier method. RESULTS: OS with UICC-NS and number of
      case were, respectively, 87.8% and 968 for pN0, 83.9% and 93 for pN1a, 71.6% and
      190 for pN1bi, 60.0% and 25 for pN2, 58.8% and 51 for pN1bii, 55.7% and 238 for
      pN1biii, 54.2% and 24 for pN1biv, 44.8% and 58 for pN3, and 20.6% and 34 for pM
      (LYM). Differences between pN1a and pN1bi and pN3 and pM (LYM) were significant
      (p < 0.05). In JBCS-NS, they were 87.8% and 968 for n0, 75.3% and 384 for n1
      alpha, 51.3% and 152 for n1 beta, 46.6% and 141 for n2, 21.2% and 33 for n3, 0%
      and 2 for n4d and n4i, respectively. Differences between n0 and n1 alpha, n1
      alpha and n1 beta, and n2 and n3 were significant (p < 0.05). CONCLUSIONS: With a
      large number of classification factors, UICC-NS was more complicated and hard to
      show significant difference in OS than JBCS-NS. But the latter also had redundant
      classifications. So, it is necessary to establish a new, simple, and easy-to
      register node classification in future.

PMID- 11320517
TI  - Paget disease of the breast--an easily overlooked disease?
AB  - BACKGROUND AND OBJECTIVES: Paget disease of the breast has long been recognized
      as a distinct clinical disease. The clinical manifestations and outcomes of Paget
      disease of the breast were reviewed to understand its earlier diagnostic clues
      and achieve an optimal treatment plan. Patients and Methods Thirty-one patients
      with Paget disease of the breast were included in this study. The postoperative
      outcomes and possible related prognostic factors were reviewed and analyzed.
      RESULTS: The 5-year overall survival was 69%. Nineteen patients (61%, Group A)
      did not have a palpable breast mass and 12 patients (39%, Group B) had a palpable
      breast mass. There was significant difference (P < 0.01) in the 5-year overall
      survival between Group A (94%) and Group B (19%). Group A patients had
      significantly higher incidences of underlying noninvasive breast carcinoma (73%
      vs. 8%, P < 0.01) and n0 lymph nodes status (84%vs. 50%, P = 0.043) than those of
      Group B. CONCLUSIONS: Paget disease of the breast without a palpable breast mass
      carries a more favorable prognosis. Patients with any nipple complaints deserve a
      detailed evaluation even in the absence of a palpable breast mass in order not to
      overlook a favorable disease.

PMID- 11320518
TI  - The prognostic significance of preoperative serum CA 19-9 in patients with
      resectable gastric carcinoma: comparison with CEA.
AB  - BACKGROUND AND OBJECTIVES: In this study, the prognostic value of pre-operative
      serum levels of tumor markers CA 19-9 and carcinoembryonic antigen (CEA) in
      gastric carcinoma which has been a controversial matter was investigated.
      METHODS: Preoperative serum CA 19-9 (cut-off value 37 U/ml) and CEA (cut-off
      value 5 ng/ml) levels were measured in 168 patients with resectable gastric
      carcinoma. The correlation between tumor marker levels and clinicopathological
      features and overall survival was studied. RESULTS: CA 19-9 and CEA positivity
      rates were 31.5 and 17.8% respectively. In CA 19-9 positive patients, the ratio
      of males, tumors exceeding subserosa and advanced stage tumors (stages III and
      IV) was significantly higher (P = 0.052, P = 0.0005 and P= 0.029, respectively).
      A weak correlation was found with CA 19-9 positivity and tumor location; however,
      no correlation existed between CA 19-9 positivity and age, tumor size, histologic
      type, lymph node, hepatic and peritoneal metastasis. The proportion of tumors
      extending beyond subserosa and with lymph node metastasis was significantly
      higher in CEA positive patients (P = 0.011 and P = 0.045, respectively). No
      correlation was found between CEA positivity and gender, age, tumor location,
      tumor size, and hepatic and peritoneal metastasis; however, a weak correlation
      existed between CEA positivity and histologic type and tumor stage. Overall
      survival was significantly poorer in CA 19-9 and CEA positive patients (log-rank
      test, P = 0.014, P = 0.003, respectively). However, the Cox proportional hazards
      regression analysis did not show independent prognostic value for both tumor
      markers. CONCLUSIONS: In resectable gastric carcinoma, preoperative serum CA 19-9
      and CEA levels may indicate stage of the disease, but neither has an independent
      prognostic value.

PMID- 11320519
TI  - Pathology and prognosis of mucinous gastric carcinoma.
AB  - BACKGROUND AND OBJECTIVES: Clinicopathologic characteristics of mucinous gastric
      carcinoma (MGC) are unclear, and whether surgical results of MGC are unfavorable
      is controversial. Pathology and prognosis of patients with MGC were studied using
      multivariate analysis. METHODS: The study included 17 patients with MGC and 614
      with nonmucinous gastric carcinoma (NGC). The tumor was defined as MGC when more
      than one half of tumor area had mucin pools. Patients were evaluated with regard
      to age, sex, tumor location, size, gross type, depth of wall invasion, lymph node
      metastasis, lymphatic and vascular permeations, stage of disease, and operative
      curability. RESULTS: MGC tumors, when compared with NGC tumors, were featured by
      the large size (9.0 vs. 5.2 cm), grossly infiltrative type (76 vs. 30%), T2 or
      more invasion (100 vs 53%), positive lymph node metastasis (88 vs. 32%),
      lymphatic permeation (94 vs. 55%), vascular permeation (47 vs. 25%), and stages
      III and IV (88 vs. 32%). On a multivariate analysis, mucinous histologic type was
      not an independent prognostic factor. Although 5-year survival rate for all MGC
      patients was lower than that for all NGC patients, the survival rate was not
      different between the MGC and NGC patients when compared in the same category of
      tumor size, depth of wall invasion, lymph node metastasis, and stage.
      CONCLUSIONS: MGC is rare and detected mostly in an advanced stage. Mucinous
      histologic type itself is not a prognostic significance in patients with gastric
      carcinoma, and the biologic behavior of MGC is similar to that of ordinary
      advanced gastric carcinoma.

PMID- 11320520
TI  - Prognosis of T4 gastric carcinoma patients: an appraisal of aggressive surgical
      treatment.
AB  - BACKGROUND AND OBJECTIVES: Despite precipitous drop in the incidence of gastric
      carcinoma in Japan, it is still one of the leading causes of death associated
      with malignant disease. Once the contiguous organs are involved the prognosis
      becomes dismal. Prognostic factors governing the survival of patients with T4
      gastric carcinoma remain unclear. METHODS: Between 1980 and 1998, 150 patients
      were treated for T4 gastric carcinoma. Results and prognostic factors were
      evaluated by univariate and multivariate analyses. RESULTS: With a 73%
      resectability, patients with tumor resection had a significantly (P < 0.0001)
      improved survival rate. Within an acceptable operative mortality (2.6%),
      apparently curative cases had survival benefit (P < 0.0001) over noncurative
      cases. In the multivariate analysis, the death risk increased by 2.18 (relative
      risk) when splenectomy was spared from the operative procedure (P < 0.0071).
      Presence of esophageal invasion was the other independent prognostic factor in T4
      gastric carcinoma patients (relative risk 2.11). Conventional prognostic factors
      along with the type of organs invaded by the carcinoma had no impact on
      prognosis. CONCLUSIONS: Patients with T4 gastric carcinoma might be benefited
      from aggressive surgery with a curative intent. Whenever possible, splenectomy
      should be done along with invaded organ resection.

PMID- 11320521
TI  - Epidemiologic differences between women with colorectal cancer and women with
      ovarian cancer.
AB  - BACKGROUND AND OBJECTIVES: The difference between the epidemiologic features of
      women with colorectal cancer and those with ovarian cancer has not been
      thoroughly studied. The aim of this study is to review the epidemiologic features
      of women with colorectal cancer and compare them with those of women with ovarian
      cancer. METHODS: The epidemiologic features of 705 women with colorectal cancer
      were compared with those of 503 women with primary epithelial ovarian cancer.
      Both groups included all women with the confirmed respective histologic diagnoses
      admitted to Roswell Park Cancer Institute between 1982 and 1996 who returned a
      voluntary self-administered epidemiologic questionnaire. RESULTS: Women with
      ovarian cancer were significantly younger, had higher education and income, had
      fewer children, and were more likely to have never been married and nulligravid
      than those with colorectal cancer. There was a significant difference in the
      contraceptive history between both groups among women > or = 45 years of age.
      More women with ovarian cancer had a family history of ovarian cancer and more
      women with colorectal cancer had a family history of colorectal cancer.
      CONCLUSIONS: The epidemiologic features of women with colorectal cancer are
      different from those with ovarian cancer. The difference between both groups
      might indicate difference in the environmental or genetic etiology of both
      cancers.

PMID- 11320522
TI  - Solid-pseudopapillary tumor of the pancreas (Frantz tumor) in children: report of
      four cases and review of the literature.
AB  - BACKGROUND: Solid-pseudopapillary tumor of the pancreas (SPT) is an exceptionally
      rare neoplasm in children. Its origin remains enigmatic. It is of low malignant
      potential and occurs most frequently in young females. PATIENTS AND METHODS: A
      cumulative review of the tumor's clinicopathological characteristics from the
      world's literature is presented. The clinical course, pathohistologic data and
      outcome of surgery of four Austrian children treated at the general hospital of
      Vienna are analyzed. RESULTS: Between 1987 and 1999, four girls (age: 12--16
      years) with SPT were diagnosed at our institution. All patients presented with an
      abdominal mass and uncharacteristic abdominal pain. Two tumors were located in
      the tail, one in the body and tail and one in the head of the pancreas (diameter:
      7--15 cm). Surgical procedures included three distal pancreatectomies and one
      partial duodenopancreatectomy (Whipple procedure). One patient had two
      recurrences with metastases that could only be partially resected. Chemotherapy
      was initiated for this patient. In the follow-up period (range: 6 months to 12
      years) all patients are alive with no evidence of recurrence. CONCLUSIONS: SPT is
      a rare differential diagnosis of a pancreatic mass in children. It is mandatory
      to establish this diagnosis since complete surgical removal of the tumor even in
      case of metastases or local invasion offers an excellent prognosis.

PMID- 11320523
TI  - Intraductal cooling of the main bile ducts during intraoperative radiofrequency
      ablation.

PMID- 11320524
TI  - Treatment of neoplastic diseases of the sacrum.
AB  - Sacral neoplasms constitute a wide range of pathological entities including
      primary and metastatic as well as benign and malignant conditions. Often these
      lesions are large at the time of initial diagnosis and surgical cure may be
      difficult. Nonetheless, surgery may be indicated for a wide range of reasons
      including tissue diagnosis, palliation of pain, preservation of neurological
      function, or attempts for curative resection. There are numerous surgical
      approaches to lesions of this area which require a complete understanding of the
      neural, pelvic, and bony anatomy. For this reason we utilize a multidisciplinary
      team approach when treating these lesions. This allows for the combination of
      expertise from areas such as general surgery, orthopedic surgery, and
      neurosurgery that optimizes the treatment of these patients. In this article we
      review the basic techniques of diagnosis and treatment of these lesions. This
      overview includes the relative anatomy, symptoms, diagnosis, imaging, operative
      indications, surgical approaches, and potential complications.

PMID- 11320525
TI  - Mucin production as a prognostic factor in resected pancreatic carcinoma.

PMID- 11320526
TI  - Why are the genes that cause risk of human neural tube defects so hard to find?

PMID- 11320527
TI  - A screen for mutations in human homologues of mice exencephaly genes Tfap2alpha
      and Msx2 in patients with neural tube defects.
AB  - BACKGROUND: Very little is known about the identity of genetic factors involved
      in the complex etiology of nonsyndromic neural tube defects (NTD). Potential
      susceptibility genes have emerged from the vast number of mutant mouse strains
      displaying NTD. Reasonable candidates are the human homologues of mice
      exencephaly genes Tfap2alpha and Msx2, which are expressed in the developing
      neural tube. METHODS: A single-strand conformation analysis (SSCA) mutation
      screen of the coding sequences of TFAP2alpha and MSX2 was performed for 204
      nonsyndromic NTD patients including cases of anencephaly (n = 10), encephalocele
      (n = 8), and spina bifida aperta, SBA (n = 183). A selected number of SBA
      patients was additionally tested for specific mutations in MTHFD, FRalpha, and
      PAX1 already shown to be related to NTD. RESULTS: Two TFAP2alpha point mutations
      in individual SBA patients were silent on the amino acid level (C308C, T396T). On
      nucleic acid level, these mutations change evolutionary conserved codons and thus
      may influence mRNA processing and translation efficiency. One SBA patient
      displayed an exonic 9-bp deletion in MSX2 leading to a shortened and possibly
      less functional protein. None of these mutations was found in 222 controls. Seven
      polymorphisms detected in TFAP2alpha and MSX2 were equally distributed in
      patients and controls. Patients with combined heterozygosity of an exonic MSX2
      and an intronic TFAP2alpha polymorphism were at a slightly increased risk of NTD
      (OR 1.71; 95% CI 0.57-5.39). CONCLUSIONS: Although several new genetic variants
      were found in TFAP2 and MSX2, no statistically significant association was found
      between NTD cases and the new alleles or their combinations. Further studies are
      necessary to finally decide if these gene variants may have acted as
      susceptibility factors in our individual cases.

PMID- 11320528
TI  - Description and mission evaluation of the Hungarian case-control surveillance of
      congenital abnormalities, 1980-1996.
AB  - BACKGROUND: The Hungarian Case-Control Surveillance of Congenital Abnormalities
      was established in 1980. This article describes how the Hungarian Case-Control
      Surveillance of Congenital Abnormalities was first organized and is currently
      maintained. The baseline statistics are provided and potential venues of
      postmarketing surveillance of drug teratogenicity and other public health tasks
      and research are proposed. METHODS: Cases with congenital abnormalities and
      patient controls with Down syndrome were selected from the Hungarian Congenital
      Abnormality Registry. Population controls without congenital abnormalities were
      selected from the National Birth Registry on the basis of three matching
      criteria: sex, week of birth, and district of parent's residence. Three sources
      of information concerning drug exposures, maternal disorders, and pregnancy
      complications, among others, were used: (1) prospective and medically recorded
      data from antenatal care logbooks and discharge summaries; (2) retrospective
      maternal self-reported data obtained with a structured questionnaire in all the
      three study groups; and (3) data collected by regional nurse in house visits to
      nonrespondent cases and patient controls. Twenty-five congenital abnormality
      groups were evaluated. During the 17-year period of data collection, 22,843
      cases, 38,151 population controls, and 834 patient controls were incorporated
      into the data set, constituting the largest population-based case-control data
      set of congenital abnormalities to date. RESULTS: Demographic features of
      pregnant women and informative offspring are presented along with the
      distribution of 25 main groups of congenital abnormalities. CONCLUSIONS: This
      system is appropriate for postmarketing the surveillance of drug teratogenicity,
      for the improvement of congenital abnormality diagnosis, to get informed consent,
      to have a communication with parents and to provide material for research.

PMID- 11320529
TI  - Pregnancy outcome after gestational exposure to metronidazole: a prospective
      controlled cohort study.
AB  - BACKGROUND: Metronidazole is an important antibacterial agent commonly used in
      women of reproductive age. Its use in pregnancy is a reason for concern for women
      and their health care providers. The objective was to examine the fetal safety of
      metronidazole. METHODS: The Israeli Teratogen Information Service prospectively
      collected and followed up 228 women exposed to metronidazole in pregnancy, 86.2%
      of whom with first-trimester exposure. Pregnancy outcome was compared with that
      of a control group, who were counseled during the same period for nonteratogenic
      exposure. RESULTS: There was no difference in the rate of major malformations
      between the groups (3/190; 1.6% [metronidazole] vs. 8/575; 1.4% [control], P =
      0.739). The rate of major malformations did not differ between the groups even
      after including elective terminations of pregnancy due to prenatally diagnosed
      malformations (5/192; 2.6% [metronidazole] vs. 12/579; 2.1% [control], P =
      0.777). A reduced neonatal birth weight was found in the metronidazole group
      compared with controls without significant differences in the rate of prematurity
      or in gestational age at delivery. The mean birth weight was lower in the
      metronidazole group when comparing the subgroup of term infants. CONCLUSIONS:
      This study confirms that metronidazole does not represent a major teratogenic
      risk in humans when used in the recommended doses.

PMID- 11320530
TI  - Induction of embryonic dysmorphogenesis by high glucose concentration, disturbed
      inositol metabolism, and inhibited protein kinase C activity.
AB  - BACKGROUND: Exposure to a diabetic environment causes excess reactive oxygen
      species (ROS), decreased prostaglandin E(2) (PGE(2)) concentration, and increased
      embryonic maldevelopment. The aim of the present work was to study whether
      embryonic dysmorphogenesis is also dependent on alterations of inositol and
      associated intracellular metabolites. METHODS: Day 9 rat embryos were cultured
      for 24 or 48 hr and evaluated for gene expression. Day 10 and day 11 embryos from
      normal and diabetic rats were also examined. RT-PCR was used to study embryonic
      gene expression of protein kinase C (PKC) and cytosolic phospholipase A(2)
      (cPLA(2)). RESULTS: Embryos exposed to 30 mmol/L glucose (30G), 500 or 750
      micromol/L of scyllo-inositol (500SI or 750SI) had higher malformation score than
      control embryos cultured in 10 mmol/L glucose (10G). Adding 1.6 mmol/L inositol
      to the 30G or 750SI culture medium partly corrected these embryos, and completely
      normalized 500SI embryonic development. Adding 0.5 mmol/L N-acetylcysteine (NAC)
      or 280 nmol/L PGE(2) protected, and failed to protect, the SI-exposed embryos,
      respectively. 10G embryos exposed to the PKC inhibitor GF-109203X displayed dose
      dependent dysmorphogenesis. Addition of 1.6 mmol/L inositol or 0.5 mmol/L NAC to
      the PKC-inhibitor-exposed 10G embryos largely normalized the outcome, whereas
      PGE(2) again failed to protect embryonic development. 30G culture tended to
      decrease the expression of cPLA(2) after 24 hr in vitro. We also found decreased
      mRNA levels of cPLA(2) in offspring of diabetic rats on gestational day 10 and of
      PKC on day 11, as compared with normal offspring. CONCLUSIONS: High glucose
      concentration causes dysmorphogenesis in embryos by an interaction of oxidative
      stress and inositol depletion.

PMID- 11320531
TI  - 1999 Warkany lecture: improving the science for predicting risks to children's
      health.

PMID- 11320532
TI  - How MRI and MRS can probe tissue microstructure far below the spatial dimensions
      of a voxel.

PMID- 11320533
TI  - Magnetization transfer in MRI: a review.
AB  - This review describes magnetization transfer (MT) contrast in magnetic resonance
      imaging. A qualitative description of how MT works is provided along with
      experimental evidence that leads to a quantitative model for MT in tissues. The
      implementation of MT saturation in imaging sequences and the interpretation of
      the MT-induced signal change in terms of exchange processes and direct effects
      are presented. Finally, highlights of clinical uses of MT are outlined and future
      directions for investigation proposed.

PMID- 11320534
TI  - Magnetization transfer MRS.
AB  - This review deals with magnetization transfer (MT) effects observed in in vivo
      NMR spectroscopy. The basic experimental methods of MT experiments, the
      underlying kinetic mechanisms as well as the evaluation of measured data by fits
      to two- or three-pool models are described. Experimental results of both (31)P
      and (1)H in vivo MRS are reviewed showing the potential of MT experiments to
      characterize kinetic equilibrium reactions. This includes reactions where all
      involved components are MR visible, as well as situations where one indirectly
      measures pools of bound spins which cannot directly be observed in vivo. In
      particular, MT effects are described which have been observed in in vivo (1)H NMR
      spectra measured on the animal or human brain or on skeletal muscle. Possible
      mechanisms for the strong MT effects observed for the signals of
      creatine/phosphocreatine, lactate, alcohol and other metabolites are discussed.
      It is also emphasized that MT effects caused by water suppression techniques may
      lead to systematic errors in the quantification of in vivo (1)H NMR spectra.

PMID- 11320535
TI  - The effects of microscopic tissue parameters on the diffusion weighted magnetic
      resonance imaging experiment.
AB  - This review examines the way in which microscopic tissue parameters can affect MR
      experiments which are sensitive to diffusion. The interaction between the intra-
      and extravascular as well as that between the intra- and extracellular spaces is
      examined. Susceptibility gradients due to the presence of deoxyhemoglobin can
      cause diffusion-induced signal losses which are significant in functional
      magnetic resonance experiments, particularly at higher main magnetic field
      strengths. This is also true of the fast response that manifests itself as an
      early negative signal change in functional magnetic resonance experiments. The
      fields surrounding paramagnetic vessels are described and the way in which
      diffusion in these fields contributes to functional signal changes is examined.
      Flow in the capillary bed can be a confounding factor in experiments which aim to
      examine the diffusion characteristics of extravascular water. It is potentially
      also a method for assessing capillary perfusion. The intravoxel incoherent motion
      experiment is described in terms of how significantly this effect can influence
      diffusion attenuation curves from water. The major models for describing water
      diffusion in tissue are presented, as are the main experimental results that have
      contributed to an understanding of the mechanisms of diffusion contrast. The
      widely accepted view that changes in the diffusion characteristics are caused by
      a shift of water to the intracellular space and a concomitant change in
      extracellular tortuosity is examined critically. More recent experiments that
      indicate that a reduction in the intracellular diffusion may occur simultaneously
      with the cell swelling are described and their compatibility with existing models
      discussed.

PMID- 11320536
TI  - Diffusion NMR spectroscopy.
AB  - MR offers unique tools for measuring molecular diffusion. This review focuses on
      the use of diffusion-weighted MR spectroscopy (DW-MRS) to non-invasively
      quantitate the translational displacement of endogenous metabolites in intact
      mammalian tissues. Most of the metabolites that are observed by in vivo MRS are
      predominantly located in the intracellular compartment. DW-MRS is of fundamental
      interest because it enables one to probe the in situ status of the intracellular
      space from the diffusion characteristics of the metabolites, while at the same
      time providing information on the intrinsic diffusion properties of the
      metabolites themselves. Alternative techniques require the introduction of
      exogenous probe molecules, which involves invasive procedures, and are also
      unable to measure molecular diffusion in and throughout intact tissues. The
      length scale of the process(es) probed by MR is in the micrometer range which is
      of the same order as the dimensions of many intracellular entities. DW-MRS has
      been used to estimate the dimensions of the cellular elements that restrict
      intracellular metabolite diffusion in muscle and nerve tissue. In addition, it
      has been shown that DW-MRS can provide novel information on the cellular response
      to pathophysiological changes in relation to a range of disorders, including
      ischemia and excitotoxicity of the brain and cancer.

PMID- 11320538
TI  - Relaxation times and microstructures.
AB  - A discussion is presented of the evaluation of multiple relaxation components
      from water protons in biological tissue. The principal focus is to draw attention
      to the way in which limitations in the raw NMR data, such as signal-to-noise
      ratio, data sampling density and acquisition window width, affect the precision
      and resolution in the processed multiple component solution of the return to
      thermal equilibrium. The second issue discussed is the interpretation of these
      multiple components in terms of microstructural compartments of the biological
      sample and, thirdly, we outline some of the successes in determining regional and
      pathological variations in microstructure in the human body in-vivo, using the
      technique of multiple relaxation components.

PMID- 11320537
TI  - Multiquantum filters and order in tissues.
AB  - In ordered systems, where the molecular motion is anisotropic, quadrupolar and
      dipolar interactions are not averaged to zero. In such cases, double quantum (DQ)
      coherences can be formed. This review deals mainly with the effect of anisotropic
      motion of water molecules and sodium ions in intact biological tissues on (2)H,
      (1)H and (23)Na NMR spectroscopy and its application to NMR imaging (MRI). Double
      quantum filtered (DQF) spectra of water molecules and sodium ions were detected
      in a variety of ordered biological tissues. In collagen-containing tissues such
      as ligaments, tendons, cartilage, skin, blood vessels and nerves, the DQ
      coherences are formed as a result of the interaction with the collagen fibers. In
      red blood cells and presumably also in nerve axons it stems from the interaction
      with the cytoskeleton. For (23)Na, an I = 3/2 nucleus, the DQ coherences can also
      be formed in isotropic media. By a judicial choice of the pulse angle in the DQ
      pulse sequence only the DQ coherences arising from anisotropic motion are
      detected. For I = 1 nuclei such as 2H, DQF spectra can be observed only in
      ordered structures. Thus, the observation of 2H DQF spectra is an indication of
      order. The same is true for pairs of equivalent 1H nuclei. The dependence of the
      DQF signal on the creation time of the double quantum coherences is
      characteristic to each tissue and allows signals to be resolved from different
      tissues by performing the measurements at different creation times. In this way,
      the 2H DQF signals of the different compartments of sciatic nerve were resolved
      and water diffusion in each compartment was studied independently. In the axon,
      the diffusion was heavily restricted perpendicular to the axon's long axis, a
      result from which the axon diameter could be deduced. In blood vessel walls, this
      characteristic enabled the different layers of the vessel to be viewed and
      studied under strain. For 2H, a DQF spectroscopic imaging sequence was used to
      study the orientation of the collagen fibers in the different zones of articular
      cartilage and bone plug. The effect of pressure on the fibers and their return to
      equilibrium was studied as well. In blood vessels, a DQF image was obtained and
      strain maps of the different layers were calculated. The efficiency of the 1H DQF
      imaging technique was demonstrated on a phantom of rat tail where only the four
      tendons were detected at short creation times. 1H DQF imaging and spectroscopy
      followed the healing of a rabbit's ruptured Achilles tendon and the results were
      far more sensitive to the process than conventional imaging. Finally, the method
      was implemented on a commercial whole body MRI spectrometer. Images of human
      wrist and ankle showed a positive contrast for the tendons and ligaments,
      indicating the potential of the method for clinical imaging. (c) 2001 John Wiley
      & Sons, Ltd.

PMID- 11320539
TI  - Dipolar coupling and ordering effects observed in magnetic resonance spectra of
      skeletal muscle.
AB  - Skeletal muscle is a biological structure with a high degree of organization at
      different spatial levels. This order influences magnetic resonance (MR) in vivo
      in particular 1H-spectra-by a series of effects that have very distinct physical
      sources and biomedical applications: (a) bulk fat (extramyocellular lipids, EMCL)
      along fasciae forms macroscopic plates, changing the susceptibility within these
      structures compared to the spherical droplets that contain intra-myocellular
      lipids (IMCL); this effect leads to a separation of the signals from EMCL and
      IMCL; (b) dipolar coupling effects due to anisotropic motional averaging have
      been shown for 1H-resonances of creatine, taurine, and lactate; (c) aromatic
      protons of carnosine show orientation-dependent effects that can be explained by
      dipolar coupling, chemical shift anisotropy or by relaxation anisotropy; (d)
      limited rotational freedom and/or compartmentation may explain differences of 1H
      MR-visibility of the creatine/phosphocreatine resonances; (e) lactate 1H-MR
      resonances are reported to reveal information on tissue compartmentation; (f)
      transverse relaxation of water and metabolites show multiple components,
      indicative of intra-, extracellular and/or macromolecular-bound pools, and in
      addition dipolar or J-coupling lead to a modulation of the signal decay,
      hindering straightforward interpretation; (g) diffusion weighted 31P-MRS has
      shown restricted diffusion of phosphocreatine; (h) magnetization transfer (MT)
      indicates that there is a motionally restricted proton pool in spin-exchange with
      free creatine; reduced availability or restricted motion of creatine is
      particularly important for an estimation of ADP from 31P-MR spectra, and in
      addition MT effects may alter the signal intensity of creatine 1H-resonances
      following water-suppression pulses; (i) transcytolemmal water-exchange can be
      studied in 1H-MRS by contrast-agents applied to the extracellular space; (k)
      transport of glucose across the cell membrane has been studied in diabetes
      patients using a combination of 13C- and 31P-MRS; and l residual quadrupolar
      interaction in 23Na MR spectra from human skeletal muscle suggest that sodium
      ions are bound to ordered muscular structures.

PMID- 11320541
TI  - Current awareness in NMR in biomedicine.

PMID- 11320540
TI  - Studies of metabolic compartmentation and glucose transport using in vivo MRS.
AB  - Organs consist of several types of cells with specialized functions. This
      cellular localization of function is often referred to as compartmentation. Due
      to the intrinsic low sensitivity of MR methods it is generally not possible in
      vivo to obtain images or spectra of single cells. Instead the MRS signal is the
      sum of the signal from millions of cells and multiple cell types. A major
      challenge in using MRS to study biological processes such as metabolism and
      transport is to devise measurements that provide cell-specific information from
      this mix. Fortunately nature has helped the MR scientist by in several cases
      nearly completely localizing metabolic pathways and their associated metabolites
      in specific cell types. The chemical specificity of MRS allows the concentrations
      and synthesis rates of these metabolites to be measured, providing information
      about the compartmentation of metabolism and function. In this review examples
      are presented from MRS studies of metabolic trafficking between neurons and
      astrocytes in the brain, brain glucose transport, and the role of muscle glucose
      transport in insulin resistance and diabetes. The concepts and approaches used in
      these studies are generally applicable for studying cellular metabolic
      compartmentation in a wide range of systems.

PMID- 11320542
TI  - [Preoperative use of nonsteroidal anti-infective agents (NSAID) in treatment of
      postoperative pain].
AB  - The purpose of the investigation was to evaluate the application of NSAiD before
      the surgical procedure and its impact on pain sensation and the amount of opioids
      and other analgetics administered to patient during the postoperation period. 60
      patients had been operated on choledocholithiasis and iguinal haemia. 20 of those
      patients were operated on cholelithiasis by using conventional method i.e.
      laparotomy, while 20 others had laparoscopic cholecystectomy. All these patients
      received general anesthesia. Another 20 patients had performed herniotomy using
      Schouldice method. They received subarachnoid blockade. Each group was devided at
      random into two subgroups consisting of 10 people each. One of them was
      administered 3 doses of NSAiD during 24 h before scheduled operation and the
      other was given placebo. To evaluate the intensity of pain the following
      parameters were used: visual analgetic scale (VAS), breath frequency, lung vital
      capacity, and total dose of opioids and other analgetics used during first and
      second day after procedure. Only patients who had been applied the same method of
      surgical treatment were compared. All the parameters, mainly VAS and the total
      dose of analgetics differed. The most visible difference was in the group of
      patients operated conventionally on cholelithiasis. Preemptive administration of
      NSAiD is justified, specially in patients before laparotomy.

PMID- 11320543
TI  - [Surgical treatment of primary liver cysts. Personal experience].
AB  - Nonparasitic liver cysts are diagnosed more often now. The aim of this study was
      to report the authors' experience with treatment for nonparasitic liver cysts.
      Retrospective review of medical records of 25 patients with hepatic cyst between
      1990 and 1999 was undertaken to determine optimal treatment. Polycystic liver
      disease (PLCD) occurred in 2 patients and remaining patients had a simple liver
      cyst. In eight patients liver cyst were diagnosed incidentally and 17 patients
      were symptomatic. Twenty one patients underwent operations: 9 open deroofing, 5
      liver resection (2 segmentectomies and 3 nonanatomical), 4 cyst excision, one
      case of laparoscopic fenestration and in 2 cases open drainage in infected liver
      cyst were performed. Four patients with asymptomatic, small (< 2 cm) hepatic cyst
      had no operative procedures--they were observed with ultrasonography control
      every six months. There were no perisurgical deaths. The symptomatic recurrence
      occurred in one patients (4.7%). The complications rate was low (4.7%)--the
      patient with PLCD had liver abscess and the open drainage were performed. Open
      surgery is safe and effective for symptomatic liver cyst and complication rate is
      low. Small and asymptomatic liver cysts should be followed up under
      ultrasonographic examination.

PMID- 11320544
TI  - [Activation of hemostasis in patients with chronic cholecystitis].
AB  - The aim of the study was to evaluate the influence of chronic cholecystitis on
      haemostasis. The study was conducted on 48 patients suffering from chronic
      cholecystolithiasis admitted for cholecystectomy to the Department of Surgery
      Regional Hospital in Bialystok. The control group consisted of 25 healthy
      subjects in this same age range. As a result of the study we found out that
      patients with chronic cholecystitis had hypercoagulability characterised by
      increase plasma concentrations of the sensitive markers of haemostasis:
      prothrombin fragments (F1 + 2), thrombin/antithrombin complex (TAT) and D-dimer.

PMID- 11320545
TI  - [The value of marker antigens TPS, SCC and CEA in diagnosis, evaluation of
      histologic type and clinical disease progression in patients with cervical
      carcinoma].
AB  - Pretreatment values TPS, SCC and CEA were measured in 84 patients with cervical
      carcinoma in order to evaluate the usefulness of markers in diagnosis, estimation
      of the histological type, estimation of stage of disease and grade of cellular
      differentiation. TPS was raised in 78.4%, SCC was raised in 71.8% and CEA was
      raised in 32.4% patients with cervical carcinoma. The frequency of increased
      results and absolute value of TPS and SCC levels showed tendency to significant
      increase with the stage of disease and to the grade of cellular differentiation.
      The highest sensitivities TPS and SCC were observed in patients with carcinoma
      planoepitheliale macrocellulare akeratodes, CEA in adenocarcinoma clarocellulare.
      These results suggest that TPS especially in the combination with SCC may be
      useful in the diagnosis and estimation of stage of disease of patients with
      cervical carcinoma.

PMID- 11320546
TI  - [Elevation of the diaphragma after cardiac surgery].
AB  - Phrenic nerve injury and diaphragmatic dysfunction can be induced by cardiac
      operation. We evaluated nonconsecutive 34 patients (pts) with elevation of the
      diaphragma after cardiac operation. 27 pts have coronary artery bypass grafting,
      7 pts have prosthetic valve implantation. We have impression that ice/saline
      slush used along with cold cardioplegia for heart arrest can cause hypothermic
      damage of phrenic nerve. Palsy of that nerve results in raised hemidiaphragm and
      delayed recovery of the pts. In our pts normalisation of the diaphragm we
      observed 6 months after operation in 41% pts and 12 month after in 93% pts. We
      suggest that results depends on early and well rehabilitation.

PMID- 11320547
TI  - [Evaluation of surgical flaps used for creation of an artificial penis in female
      male type transsexuals].
AB  - In the years 1983-1997, 252 female to male transsexuals were treated in the
      Department of Plastic Surgery of University Medical School in Lodz. In 209
      patients surgical penis construction was performed. The paper presents operative
      techniques and results of penis construction with the use of four kinds of flaps:
      a bipedicled abdominal tube flap, a single pedicled infraumblical flap, a
      pedicled myocutaneous flap with gracilis muscle and a pedicled lateral groin
      flap. Overall estimation of early results of penis construction with the use of
      the four methods applied in the Department showed that we obtained good results
      in 69.8% of operated transsexuals, satisfactory effects in 24.4% of patients and
      poor outcome in 5.8% of cases. The best results were achieved with the technique
      involving a lateral groin flap.

PMID- 11320548
TI  - [Psychologic factors for imminent lower extremity pain caused by peripheral
      angiopathy disorders in middle-age and elderly persons].
AB  - The aim of the study was to determine factors of pain threat in lower extremities
      caused by peripheral angiopathy disorders using the following psychometric
      methods: Cattell's 16 PF, Gough's CPI, and Gough and Helibrun's ACL-37 with the
      instructions: This is how I was This is how I am. In the comparative inter- and
      intra-group analysis the following risk factors were identified: active way of
      life, self-control, balance, self awareness free from dependence on the social
      environment and defense mechanisms and such needs as dominance, order, change,
      which can become a guarantee of a more effective pharmacological treatment. In
      the application consideration was given to legitimacy of those factors in
      prevention of such pain caused by peripheral angiopathy vessels.

PMID- 11320549
TI  - [Psychologic disorders in acute and persistent neuroborreliosis].
AB  - In the risk group, inhabiting endemic areas, even non-specific symptoms should
      alert the physician to the possibility of infection caused by the spirochete. The
      invasion of central nervous system (neuroborreliosis) may be the cause for
      persisting, irreversible intellectual impairment and memory deficits. Brain
      lesions are the result of misdiagnosis and delayed antibiotic treatment. This
      paper describes a case of neuroborreliosis with atypical beginning and diagnostic
      difficulties.

PMID- 11320550
TI  - [Acute pancreatitis].
AB  - The care of patients with acute pancreatitis is complex. This review summarizes
      the etiopathogenesis, prognosis, nonoperative management of patients with acute
      pancreatitis, the importance of nutrition in patients with severe acute
      pancreatitis and the role of monitoring and rationale of endoscopic and surgical
      intervention.

PMID- 11320551
TI  - [Secretin. New views on the oldest digestive system hormone].
AB  - For many years secretin, discovered in 1902, has been known as a hormone taking
      part in the digestion process. In the 70-ties the effects of secretin in other
      organs than gastrointestinal tract were observed. This fact and identification of
      a new hormone of gastrointestinal tract, VIP, that resembles the structure and
      function of secretin have initiated the new era of research work. The sites
      binding this hormone were found in different organs and the role of stimulation
      of secretin receptors coupled with G protein were studied. Recently a new
      classification of the hormones of gastrointestinal tract has differentiated
      peptides of the secretin family.

PMID- 11320552
TI  - [Allogeneic transplantation in reconstruction of cruciate ligaments in the knee
      joint].
AB  - Allografts have been used successfully by orthopaedic surgeon for reconstructing
      ligaments, including intraarticular reconstructions of cruciate ligaments. This
      type of grafts are particularly attractive alternative for reconstruction surgery
      because donor site morbidity is eliminated, operative time is shorter, incision
      can be smaller and the availability of different transplant sizes is almost
      unlimited. This article offers some summaries of scientific background on ACL
      reconstruction with allografts in animals, clinical follow-up in the humans and
      discussions on the risk of disease transmission, secondary sterilization,
      incorporation and remodeling of the allografts after transplantation.

PMID- 11320553
TI  - [Pathogenesis and clinical characteristics of cytomegalovirus infection].
AB  - The general characteristics of cytomegalovirus (CMV), one of a member of the
      family Herpesviridae has been described. Epidemiologic findings, especially CMV
      infection rates in normal individuals and different risk groups, as well as
      sources of infection have been discussed. The article presented clinical
      syndromes associated with CMV infection in normal host, infants, blood products
      and allograft recipients, HIV-positive and undergoing immuno-suppressive therapy
      patients.

PMID- 11320554
TI  - [Hirsutism--difficult diagnostic and treatment problem].
AB  - In the study, in concise way, actual knowledge concerning hirsutism was
      presented. Its causes, forms, diagnostic proceeding and methods of treatment were
      discussed.

PMID- 11320555
TI  - [Homocysteine--new risk factor for progression of atherosclerosis and its
      complications].
AB  - The main cause of mortality and morbidity in Europe and United States are
      cardiovascular diseases. Besides well known atherogenic risk factors there has
      recently been a lot of attention paid to homocysteine. It is a sulfur aminoacid
      which is the demethylation product of methionine. Many facts support the role of
      this agent in development of arteriosclerosis and its sequelle. The relation of
      hyperhomocysteinemia with vascular complications, therapeutic options and
      potential atherogenic mechanisms are discussed in this paper. Special attention
      was paid to chronic renal failure patients.

PMID- 11320556
TI  - [Progress in rehabilitation of dizziness and equilibrium disorders].
AB  - Physiopathological basics of vestibular rehabilitation are based on mechanisms of
      vestibular compensation. In the course of vestibular organ lesion compensation
      can be achieved sooner through increased activity of the patient in habituation
      process, with active contribution of the vision and proprioceptive organs. The
      criteria of qualification and preparation of the patients were presented. The
      role of creation of adequate motivation of the subject in the process of
      preparation was emphasised. The progresses that had been achieved in this
      treatment method were mentioned. The value of individual training programs, that
      is programs adapted to definite needs of the patients, was appreciated in recent
      years. It was revealed, that training programs directed to train certain system
      such as lower limbs strength, failure of vestibular receptor, gait disturbances
      bring significant improvement in such cases. However traditional exercises
      consisting in the whole body movements do not bring desirable effects in certain
      cases. The new methods of assessment of rehabilitation progress were presented.
      Those methods are based on receding of subjective symptoms during normal daily
      activities.

PMID- 11320557
TI  - [Significance of medium molecular weight peptides in pathologic processes].
AB  - The literature concerning of prevalence and meaning of middle molecular peptids
      in experimental and clinical pathology has been reviewed. Middle molecular
      peptids have been extracted for the first time from plasma of the patients with
      renal insufficiency by Babb in 1970.

PMID- 11320558
TI  - [Significance of cathepsin B and D in physiologic and pathologic processes].
AB  - The lysosomal proteases play an important role in the cells nourishment,
      immunogenesis, development of the arteriosclerosis perturbations in blood vessel
      cells and in the pathogenesis of degeneration diseases, cancer diseases and in
      the great number of others. For the many cancer disease durations, an increased
      activity of the lysosomal enzymes both in blood serum and in tumor tissues was
      revealed. Over the past few years a particular attention have been paid to the
      fact that the high activity of some lysosomal enzymes i.e. cathepsin B and D is
      connected with the increased cancer invasiveness. The results of preliminary
      clinical research point to great diagnostic value of cathepsin B and D in breast
      cancer detection.

PMID- 11320559
TI  - [The effect of electromagnetic fields on blood coagulation and fibrinolysis in
      humans].
AB  - Reports concerning a decrease of blood fibrinolytic activity in humans during
      electromagnetic storms, abortions in women working with or near screen monitors
      and sudden cardiac death in locomotive drivers, decided to examine the
      coagulation and fibrinolytic systems in workmen staying in areas of
      electromagnetic waves--25 locomotive drivers, 23 persons working with monitors
      and control groups. The result of the performed studies allowed me to draw the
      following conclusions: 1) Professional contact with electromagnetic fields had
      its influence upon changes in the coagulation and fibrinolytic systems in the
      examined persons. 2) Increased activity of inhibitor of plasminogen activator
      (PAI-I), the main factor inhibiting fibrinolysis is ascertained in both
      investigated groups. 3) Precise knowledge concerning PEM influence on the
      examined systems has its prophylactic and epidemiologic significance.

PMID- 11320560
TI  - [Genetic factors in sarcoidosis].

PMID- 11320561
TI  - [Comparison of HLA class I and DR class II antigen frequency in Polish patients,
      in relation to different stages of the disease].
AB  - The aim of this study was to analyze the association between HLA class I and
      class II DR frequency in the different stages of sarcoidosis in Polish
      population. 88 patients and 30 healthy controls have been typed. Patients were
      divided into three groups depending on radiological findings. In the first group
      were 28 cases presenting the regression of the disease. In the second were 33
      patients in stable stage II or III and in the third group 27 patients with
      pulmonary fibrosis (stage IV). The typing was performed by NIH method using
      commercial sera. There were no statistically significant differences between
      studied group in HLA-A class I. The frequency of HLA B-18 was statistically more
      frequent in patients with sarcoidosis compared to healthy controls. HLA-DR1 was
      not present in third group of patients and the difference was significant
      compared to healthy controls.

PMID- 11320562
TI  - [Familial sarcoidosis in Poland: analysis of clinical characteristics and
      environmental aspects].
AB  - Sarcoidosis is a systemic disease of undetermined etiology although it can be
      related to genetic or environmental factors or both. We investigated 19 polish
      caucasian families with at least two affected relatives and healthy families
      members in order to evaluate the clinical aspects of familial sarcoidosis and the
      influence of environmental factors. We have found three types of familial
      sarcoidosis: 10 sib pairs, 1 sib triplet, 5 parent offspring pairs and one case
      of sarcoidosis in cousins. Most of sarcoidosis cases were histologically proved.
      A high frequency of chronic onset of the disease, chronic form with
      extrapulmonary sarcoidosis and fibrosis were observed. In only three families the
      course of the disease was similar in both affected relatives. There was no
      specific environmental agent found that could be related to the development of
      the disease. We concluded that it may be possible that familial sarcoidosis can
      have poorer prognosis that non-familial form, but there is no epidemiological
      data available about the clinical aspects of sarcoidosis in Poland. The clinical
      aspects of familial sarcoidosis can suggest the inherited susceptibility to the
      disease. The etiologic extrinsic factor has not been identified, but it doesn't
      exclude its role in the pathogenesis.

PMID- 11320563
TI  - [Histocompatibility class I antigens loci A and B in familial sarcoidosis in
      Poland].
AB  - Thirty three affected members from 17 Polish sarcoidosis families and their
      healthy relatives (61 subjects) have been typed for HLA class I (A and B).
      Controls consisted of 101 healthy Polish subjects. The HLA typing was performed
      by the serological method using the standard microcytotoxicity test. No
      significant differences were observed between group 1 (33 affected family
      members), group 2 (61 healthy relatives) and group 3 (healthy controls)
      considering the HLA class I locus A antigens. The frequencies of HLA B8, HLA B16
      and HLA B40 were significantly higher in affected sarcoidosis families members
      compared to control subjects (p < 0.05). When comparing all families members
      (affected and non-affected as a one group) to the control group we found a
      significant overrepresentation of HLA B12 and B35 in the control group. We
      concluded that HLA antigens locus B: B12 and B35 may have a protective function
      against the disease; the role of HLA class I antigens in the pathogenesis of
      sarcoidosis needs further evaluation.

PMID- 11320564
TI  - [Polymorphism of histocompatibility class II antigens coded with the DRB gene in
      in familial sarcoidosis in Poland].
AB  - Several studies suggested association between some human leukocyte antigen (HLA)
      alleles and sarcoidosis, but none has been conclusive. To confirm possible
      association of sarcoidosis with HLA-DRB1, -DRB3,- DRB4, -DRB5 associated alleles
      HLA-DR genotyping was performed using polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP) method in 17 polish families with
      familial sarcoidosis and in 101 healthy controls. The families with sarcoidosis
      consisted of 31 affected first-degree relatives from 16 families, 2 affected
      cousins from 1 family and 78 healthy relatives of those patients. We found 3
      varieties of familial sarcoidosis: a) in parent and offspring (5 pairs), b) in
      siblings (10 sib pairs and 1 sib triplet) and in cousins (1 family). Genotyping
      for HLA-DRB1,-DRB3,-DRB4,-DRB5 revealed an over-representation of HLA-DR5(12) and
      DRw52 among antigens shared by affected relatives comparing to the control group.
      A significant increase in the frequency of HLA-DR7 and HLA-DRw53 antigens (p <
      0.05) was found in subjects from the control group. Comparing the group of family
      members (affected and healthy relatives taken together, n = 111) with the control
      group (n = 101) we found a significant differences in the distribution of HLA
      DR2(15), HLA-DR5(12), HLA-DR6, HLA-DR9 and HLA-DRw52. Those antigens were more
      frequent (p < 0.05) in members from families with sarcoidosis. The frequencies of
      HLA-DR1, HLA-DR2(16), HLA-DR7 and HLA-DRw53 were significantly higher (p < 0.05)
      in the control group. Presented results suggest that HLA-DRB alleles contribute
      to the susceptibility to sarcoidosis in the Polish population.

PMID- 11320565
TI  - [A probe for evaluating the role of HLA class II antigens coded with the DRB gene
      in etiopathogenesis of familial sarcoidosis in Poland using the K-nearest
      neighbor experimental statistical method].
AB  - The aim of this study was evaluation of the significance of HLA-DRB1,-DRB3,-DRB4,
      DRB5 associated alleles in the genetic susceptibility to sarcoidosis. We
      investigated 17 Polish 'families with' familial occurrence of the disease. Thirty
      three affected family members and 78 healthy relatives and 101 healthy
      individuals (control group) have been typed for HLA class II DR antigens.
      Assuming that relatives from families with two or more affected members are more
      susceptible to develop sarcoidosis we considered two classes: affected and
      healthy family members taken together (class 1, N = 111) and healthy control
      group (class 2, N = 101). HLA antigens from both classes were compared using a
      statistical pattern recognition method. This method, called k-NN method, assumes
      that objects (individuals) are described by a certain number of variables called
      features. Selected features that played an important role in the decision to
      which class an individual person would be classified were: HLA-DR7, HLA-DR2(16),
      HLA-DR1, HLA-DR5(12), HLA-DR6(14), HLA-DR6(13), HLA-DR9, HLA-DR5(11) and HLA
      DRw52. K-NN method allowed to classify properly 76% of studied subjects to
      healthy or disease susceptible group. However, 24 out of 100 individuals would be
      misclassified which gives the total error rate of 0.24. We concluded that using
      HLA-DR antigens as features characterising every individual we can predict with
      high probability to which class ("high risk" or "healthy") individual would
      belong.

PMID- 11320566
TI  - [The relation between lymphocyte profile in BALF and the course of sarcoidosis
      based on short term observation].
AB  - The aim of this study was to assess how the extent of the number and percentage
      of lymphocytes in BALF and also the CD4 to CD8 ratio can help to predict the
      short outcome in sarcoidosis. Material consisted of 74 patients, 39 men and 35
      women in the age from 23 to 58 years. 11 patients had chest lesions in stage I,
      43 in stage II and 20 in stage III. Clinical markers of activity (fever, erythema
      nodosum) were present in 22 cases. Extrathoracic lesion were present in 31 and
      abnormal pulmonary function in 30. In all patients BAL was done before treatment
      and lymphocyte count, percentage and CD4/CD8 ratio was calculated. 50 patients
      were treated with corticosteroids and 24 were observed without treatment. After 6
      12 month of observation regression of sarcoid lesions was observed in 46 of 50
      patients treated with corticosteroids and in 17 out of 24 patients observed
      without treatment. There were no differences in lymphocyte count and percentage
      in BALF and in the short term outcome between group treated with corticosteroids
      and without treatment. The patients in whom regression of lesions was observed
      have however significantly higher CD4/CD8 ratio than others.

PMID- 11320567
TI  - [Atypical radiologic image of pulmonary sarcoidosis as a diagnostic problem].
AB  - Sarcoidosis is a multisystem disorder of unknown cause frequently presenting with
      hilar lymphadenopathy, pulmonary infiltration, ocular and skin lesions. Multiple
      circular or oval pulmonary dentisties appear in the less than 5% of patients. We
      describe 4 sarcoidosis cases with multiple or single tumor lesion. These patients
      were referred to our department with initial diagnosis of metastatic or primary
      lung malignancy. Two of them presented the picture of multiple tumors and two had
      single peripheral lung mass with hilar lymphadenopathy. This report shows
      difficulties in the diagnosis of the interstitial lung diseases when the
      radiological pattern mimics malignancy.

PMID- 11320568
TI  - [Pulmonary sarcoidosis diagnosed in 2 cases suspected to be neoplasms].
AB  - Two young patients suspected of neoplasms were admitted to Thoracic Surgery
      Department of Institute of Tuberculosis in first case (35-years old woman) chest
      x-ray showed atelectasis of upper right lobe, enlarged lymph nodes of mediastinum
      and right hillium-lymphoproliferative process was suspected. Repeated
      bronchoscopies revealed narrowing of upper right bronchus and in biopsy-
      granulomas with small focus of necrosis were found. Tuberculosis was not
      excluded. During short antituberculous treatment progression of lung lesions and
      enlarged supraclavicular lymph node were observed. Following biopsy confirmed
      sarcoidosis. Treatment with prednisone was successful. In second case the chest x
      ray showed large masses in both lungs suspected of seminoma metastases. Lung
      biopsy made during thoracotomy revealed sarcoidosis.

PMID- 11320569
TI  - [A procedure for bronchial dilatation using a balloon-based technique as a method
      for removing post-inflammatory stenosis].
AB  - 18-years old girl was admitted to hospital because of recurrent infections after
      pulmonary tuberculosis treated 4 year ago. Chest X-ray was near normal but during
      bronchoscopy--narrowing of lingula bronchi was revealed. In order to dilate the
      bronchi, a balloon, bronchoscopically directed, coming from a set designed for
      percutaneous transluminal coronary angioplasty, was applied.

PMID- 11320570
TI  - [Diagnosis and treatment of sarcoidosis].

PMID- 11320571
TI  - [The role of mast cells in inflammatory reactions].

PMID- 11320572
TI  - [Central pontine myelinolysis in an eighteen year old woman].
AB  - Central pontine myelinolysis is sporadically diagnosed disease. The disease has
      fulminant course and fatal prognosis. Myelinolysis is known for 40 years, but its
      cause remain still unclear and therapy is not established. A case of 18 year old
      woman hospitalized in the Department of Infectious Disease Medical Academy of
      Bialystoku is an example of such a difficulties.

PMID- 11320573
TI  - [Malignant fibrous histiocytoma (fibrohistiocytoma malignum) localized
      intracranially].
AB  - Primary intracranial malignant fibrous histiocytoma (MFH) is an extremely rare
      occurrence, however this kind of neoplasm is observed among the sarcomas. The aim
      of this report is to present a case of malignant fibrous histiocytoma in a 22
      years-old woman. The control examination performed five years after operation
      revealed only mild exophthalmus and visual disturbances as presented before
      surgery.

PMID- 11320574
TI  - [Chronic demyelinative polyneuropathy Guillain-Barre type in the course of
      systemic lupus erythematosus ].
AB  - The authors presented a rare case of chronic demyelinative polyneuropathy
      Guillain-Barre type in 49-year old woman with systemic lupus erythematosus. The
      diagnostic was based on electroneurographic examination and immunodiffusion of
      cerebrospinal fluid proteins. The authors indicated to the high effectiveness of
      high doses of immunoglobulins administrated intravenously after 3 months of the
      beginning of peripheral symptoms. At the onset of the disease the
      immunosuppression by use of prednisolone and cyclophosphamide was ineffective.

PMID- 11320575
TI  - [Subclinical hyperthyroidism ].
AB  - Subclinical hyperthyroidism is defined as normal thyroid hormone level in serum
      but low serum thyrotropin TSH concentration in an asymptomatic individuals. The
      article described prevalence, pathogenesis, causes, clinical symptoms and
      diagnostic criteria of subclinical hyperthyroidism and is especially focused on
      patients with this thyroid dysfunction induced increase risk for development of
      atrial fibrillation and a decrease in bone mass in the case of postmenopausal
      women. It is not clear whether and when this pathology should be treated but the
      problem is important because of 4% patients per year which can possible develop
      overt hyperthyroidism. Most of the authors conclude that a treatment is required
      in selected cases or under special circumstances only.

PMID- 11320576
TI  - [Cephalosporins in empirical treatment of neutropenic fever].
AB  - Neutropenic fever and infection became a significant clinical problem with the
      common use of chemotherapy of cancer. The cephalosporins are a large group of
      beta-lactam antimicrobial agents. Because of their broad spectrum of activity and
      low toxicity, they are excellent choice for initial empirical treatment of fever
      in neutropenia. The article summarises the role of third and fourth generation
      cephalosporins in therapy of neutropenic fever.

PMID- 11320577
TI  - [The role of free radicals in inflammatory states, ulceration, and ulcers of the
      stomach and duodenum].
AB  - The free radicals derived from oxygen have been implicated in damage caused to
      the gastroduodenal mucosa. The association between the mucosal production of
      reactive oxygen radicals in the gastric antrum and duodenum, Helicobacter pylori
      density and duodenal ulcer has been previously described. The role of interleukin
      IL-8 in the inflammatory process and its relationship with reactive oxygen
      radicals has also been investigated. These results indicate that oxygen radicals
      play an important role in the mechanism of ulcer aggravation induced by a variety
      of different factors.

PMID- 11320578
TI  - [Chemokines in meningitis of different etiologies].
AB  - Chemokines constitute a group of cytokines with strong chemotactic activity
      towards different populations of leukocytes, playing significant role in the
      pathogenesis of inflammatory responses. The chemokines of the alpha subfamily act
      mainly on neutrophiles, while beta subfamily chemokines attract primarily
      monocytes and lymphocytes. Research conducted within the last few years suggests
      chemokines to be the main factors responsible for the attraction of leukocytes to
      the cerebrospinal fluid (CSF) in the course of both bacterial and viral
      meningitis. In cerebrospinal fluid from patients with meningitis of different
      etiologies significant concentrations of both alpha and beta chemokines were
      observed, which tended to decrease after the introduction of the treatment, with
      the relationship to the clinical improvement. It was also confirmed in in vitro
      experiments that the chemotactic properties of the inflammatory CSF mainly depend
      on the presence of chemokines. The most important chemokines in the
      pathophysiology of the meningitis in humans are probably interleukin 8 (IL-8),
      monocyte chemoattractant protein (MCP-1) and INF-gamma inducible protein (IP-10).
      They seem to be responsible for the attraction to the cns of, respectively,
      neutrophiles, monocytes and activated T lymphocytes. Differences between the
      chemokine profiles observed in meningitides of different etiologies are to some
      degree relevant to coexisting differences in type and extent of pleocytosis. In
      future, measurements of concentrations of certain chemokines may become of some
      importance in diagnostics of meningitis and monitoring its clinical course.

PMID- 11320580
TI  - [The role of psychologic factors in adaptive behavior of younger and older
      people].
AB  - Contemporary view on the issue of adjustment potential in an aging human being is
      presented. In a prognostic model the following features, ranked according to
      their importance, were identified: for younger individuals--friendship, warmth,
      responsibility, thoroughness, persistence, control of conditioned and
      unconditioned reflexes, sensitivity, tenderness, wide range of interests,
      tolerance towards other people and high level of intellectual efficiency; for
      older individuals--self control, social maturity and balanced approach to the
      others, lack of conflicts in interpersonal relationships, self sufficiency and
      independence, tolerance with a tendency to self subordination and psychological
      immunity. Attention is drawn to the results of the obtained prognostic models
      which will constitute a reference base for psychologists working in geriatric
      wards.

PMID- 11320579
TI  - [Vitamin C in treatment of certain cardiovascular diseases].
AB  - The human organism is incapable of producing vitamin C by biosynthesis. We are
      therefore totally dependent on the presence of this vitamin in our diet. Vitamin
      C is capable of essentially influencing the course of many metabolic processes,
      and it is therefore used in the treatment and prophylaxis of many diseases,
      including those that are a consequence of the activity of the so-called reactive
      forms of oxygen. The presence of vitamin C in the anti-oxidant protective system
      is believed to be very important, since it can react with the free radicals of
      oxygen and other oxidants, and "sweep" them away. Therefore, attention is more
      and more frequently focused on the possibility of using vitamin C in the
      treatment of those circulatory diseases that are believed to be associated with
      the action of free radicals. Routine administration of vitamin C should be
      therefore recommended in the treatment of patients with coronary arterial
      disease, treatment of patients after cardiac infarction or cerebral stroke, or in
      the treatment of arterial hypertension.

PMID- 11320581
TI  - [The effect of influenza vaccine on the immune system in elderly persons].
AB  - Development in the area of immunology revealed new phenomena accompanying a
      vaccination against influenza. The authors discuss the mechanisms participating
      in the arising of the immunity against influenza, influence of the vaccine on the
      immune system of the elderly and also basic recommendations for vaccination.

PMID- 11320582
TI  - [Activity of cefepime compared with other antibiotics against major hospital
      bacterial pathogens].
AB  - The aim of the study was to evaluate susceptibility of 976 bacterial isolates
      from nosocomial infections to cefepime and 9 other antibiotics used in the
      treatment of hospitalised patients. Bacterial strains were mainly derived from
      wound and soft tissue infections, sputum, abscesses and blood. The most prevalent
      etiologic agents were: Pseudomonas aeruginosa (18.7%), Escherichia coli (13.8%),
      Staphyloccocus aureus (9.7%, Acinetobacter baumannii (9.12%), Klebsiella
      pneumoniae (7.38%), Enterobacter cloacae (5.6%). The most susceptible to cefepime
      were strains of K. pneumoniae (98.62%), E. coli (98.52%) and E. cloacae (98.19%)
      including those producing extended spectrum beta-lactamases. The degree of
      susceptibility to cefepime was equal to that of imipenem. A. baumannii was the
      least susceptible species (67.42%). This study indicate that cefepime may play an
      important role in therapy of nosocomial infections in particular caused by
      Enterobacteriace.

PMID- 11320583
TI  - [Analysis of voice function disorders using videostroboscopic techniques].
AB  - Clinical applications of videostroboscope in phoniatrics were investigated.
      Altogether 79 patients with functional lesions of the larynx and 20 with normal
      were examined. Measurements of vibration, amplitude, frequency and mucosal wave
      of vocal cords yielded cords objective information about vibration in the
      functional dysphonia. Videolaryngostroboscope can help identify the kind of
      functional diseases of the larynx.

PMID- 11320584
TI  - [Use of a dynamic test with HCG for evaluation of endocrine function in gonads of
      men with chronic alcohol abuse].
AB  - We studied 40 chronic alcoholic men (aged 39 +/- 11) after alcohol withdrawal. We
      excluded in these patients severe internal organs disorders (first of all liver
      dysfunction) and seminal pathology. We analysed (in HCG test) plasma levels of:
      luteinizing hormone--LH, follicle stimulating hormone--FSH, total testosterone-
      T, free testosterone--fT, estradiol--E, 17-OH progesterone, sex hormone binding
      globulin--SHBG. Our results suggest: 1) decreased testicular reserve of free
      testosterone and normal level of total testosterone, 2) decreased initial level
      and functional reserve of 17-OH progesterone, 3) mild hyperoestrogenism, 4) no
      significant difference of LH, FSH, SHBG levels between alcoholics and controls,
      5) these results were not changed after 6 months observation. These results
      indicate on subclinic alcoholic hypogonadism.

PMID- 11320585
TI  - [Some adhesion molecules in blood of patients with chronic B-cell lymphocytic
      leukemia].
AB  - Adhesion molecules actively participate in all stages of leukocyte migration,
      directly or indirectly by means of appropriate ligands. Therefore the aim of
      study was the determination of concentrations of L-selectin and ICAM-1 in cell
      culture supernatante, broken lymphocyte and plasma. The measurement of cell
      adhesion molecules (CA) concentrations were performed by means of immunoenzymatic
      kits of ELISA type in the patients with chronic lymphocytic leukaemia in the
      clinicals stages I and III. The levels of L-selectin were increased in cell
      culture supernatante but in the plasma concentrations of L-selectin were
      decreased. The behaviour of concentrations of studied substances in the broken
      lymphocytes was differently. It is possible that these investigations may appear
      useful in the future as an additional diagnostic indecks.

PMID- 11320586
TI  - [Tissue factor and it's inhibitor in patients up to 50 years of age with ischemic
      stroke].
AB  - Stroke is the third leading cause of death and an important cause of longterm
      disability. Up to 10% of stroke patients is younger than 45 years old. In the
      present study we measured and compared TF and TFPI concentrations in 50 ischemic
      stroke patients up to the age of fifty and in 30 control subjects matched for
      age. TF concentration was significantly higher in ischemic stroke patients, TFPI
      concentration did not differ compared to controls. No relationship was
      established between TF and TFPI in relation to clinical subtypes of stroke, sex,
      smoking, plasma cholesterol level, hypertension, previous stroke.

PMID- 11320587
TI  - [Familial occurrence of nephroblastoma].
AB  - Wilms' tumour can develop in ways: sporadic--non-hereditary or familial. Familial
      Wilms' tumour is not very seldom. It is a form of autosomal dominant segregation
      and probably low and variable penetration. Up to now it has not been observed in
      the presence of characteristic genetic changes. Taking into consideration the
      case of the patient with positive family interview we presented the way of
      diagnosing and treating the child. Moreover we presented the results of
      cytogenetic examination and molecular analyses (loss of heterozygosity of WT1
      gene and loss of heterozygosity 16 q), which had not shown any changes. We also
      discussed the actual level of knowledge abut familial form of Wilms' tumour.

PMID- 11320588
TI  - [Blepharospasm and Meige's syndrome--a contribution to it's pathogenesis].
AB  - Two cases with blepharospasm followed by Meige syndrome were described. In the
      first magnetic resonants revealed bilateral hypodensive foci in thalamus. During
      the few years general dystonia has been developed after several relapses of
      disease diagnosed as multiple infarcts followed by aphasia, hemiparesis and
      asynergia. In the other one, who died, loss of neurons in striatum, especially in
      caudate nuclei was found. It is concluded that blepharospasm could be a syndrome
      of different origin and only the phase of Meige syndrome.

PMID- 11320589
TI  - Management of patients with head injuries and multiple other trauma.
AB  - The management of patients with multiple trauma including head injuries is a
      complex task. The prime goal is to minimize secondary neuronal injury. Attention
      to establishment of an airway, assurance of adequate gas exchange, and
      circulatory resuscitation is mandatory to minimize any secondary neuronal
      injuries. Once these principles of resuscitation have been applied and the
      primary neuronal injury is treated, additional etiologies of secondary brain
      trauma, such as hypoglycemia and hypothermia, should be addressed. Continual
      monitoring of oxygenation and perfusion is mandatory optimizing the outcome of
      these patients.

PMID- 11320590
TI  - The nutritional management of patients with head injuries.
AB  - Severe head injuries tend to be associated with hypermetabolism and
      hypercatabolism resulting in negative nitrogen balances which may exceed 30 grams
      day-1. Enteral feeding should begin as soon as the patient is hemodynamically
      stable, attempting to reach a non-protein caloric intake of at least 30-35 kcal
      kg-1 day-1 and a protein intake of 2.0-2.5 g kg-1 day-1 as soon as possible. With
      severe head injuries (Glasgow Coma Scale < 8), there is an increased tendency for
      gastric feeding to regurgitate into the upper airway. Keeping the patient upright
      and checking residuals is important in such patients. Jejunal feedings are less
      apt to be aspirated. If it is apparent that the gastro-intestinal tract cannot be
      used to reach the nutritional goals within three days, total parental nutrition
      is begun within 24-48 h so as to reach these nutrition goals by either one or
      both routes by the third or fourth day. Blood glucose levels exceeding 150-200 mg
      dl-1 tend to increase the severity of the neurologic problems and efforts should
      be made to prevent hyperglycemia by carefully regulating the glucose and insulin
      intake. Indirect calorimetry to determine the respiratory quotient and resting
      energy expenditure should be determined twice weekly. To determine N2 balance,
      urinary urea nitrogen should be measured in 24-h specimens. These tests should be
      performed once or twice weekly until it is clear that the nutrition is adequate.

PMID- 11320591
TI  - Alterations in cerebral energy metabolism induced by traumatic brain injury.
AB  - Energy metabolism of the brain is unique, possessing high aerobic metabolism with
      no significant capacity for anaerobic glycolysis and limited tissue stores of
      glucose. A steady supply of oxygen and glucose is essential in order to maintain
      cerebral function and integrity. Extensive research in experimental and human
      head injury has been conducted regarding the delivery of oxygen and outcome. This
      research has provided evidence which indicates that in addition to the
      availability of oxygen and glucose, other factors, such as perturbation of
      mitochondrial energy transducing processes which also follow head trauma, play
      significant roles. In this paper, the salient findings from biochemical studies
      of experimental and clinical brain injury are summarized and indicate that the
      mitochondrial respiratory chain-linked oxidative phosphorylation and calcium
      transport are compromised by trauma-induced brain injury and support the idea
      that oxidative stress and perturbation of cellular calcium homeostasis play
      significant roles in traumatic brain injury.

PMID- 11320592
TI  - Acute alterations of endothelin-1 and iNOS expression and control of the brain
      microcirculation after head trauma.
AB  - The biosynthetic equilibrium between endothelin-1 (ET-1, a vasoconstricting
      agent) and nitric oxide (NO, a gas with vasodilating effects) is thought to play
      a role in the autoregulation of microvessel contractility and maintenance of
      adequate perfusion after traumatic brain injury. ET-1 is a constitutively
      expressed peptide, while the gene that encodes for the inducible nitric oxide
      synthase (iNOS, an enzyme responsible for the synthesis of excessive and toxic
      amounts of NO) is solely activated after brain injury. We employed the Marmarou
      acceleration impact model of brain injury (400 g from 2 m) to study the effect of
      closed head trauma on the rat brain microcirculation. Following head trauma we
      analyzed changes of cerebral cortex perfusion using laser Doppler flowmetry and
      ultrastructural alterations of endothelial cells. We temporally correlated these
      changes with the expression of ET-1 (immunocytochemistry) and iNOS (in situ
      hybridization) to assess the role of these vasoactive agents in vascular
      contractility and cortical perfusion. Cortical perfusion was reduced by
      approximately 50% during the second hour as compared to values during preceding
      time points after TBI, reached a peak minutes before 3 h, and subsequently showed
      a trend towards normalization. A significant reduction in the lumen of
      microvessels and severe distortion of their shape were observed after the fourth
      hour post-trauma. At the same time period ET-1 expression in endothelial cells
      was stronger than in microvessels of control animals. ET-1 expression was further
      increased at 24 h after TBI. iNOS mRNA synthesis was strongly upregulated in the
      same cells at 4 h but was undetectable at 24 h post trauma. Our combined
      functional, cellular and molecular approach supports the notion that ET-1 and
      iNOS are expressed differentially in time within individual endothelial cells of
      cortical microvessels for the control of cortical blood flow following closed
      head trauma. This differential expression further indicates a reciprocal
      interaction in the synthesis of these two molecules which may underlie the
      control of microvascular autoregulation.

PMID- 11320593
TI  - Biomechanics of neurotrauma.
AB  - This paper reviews the traditional areas of impact biomechanics as they relate to
      brain injury caused by blunt impact. These areas are injury mechanisms, human
      response to impact, human tolerance to impact and the use of human surrogates.
      With the advent of high-speed computers, it is now possible to add computer
      models to the list of human surrogates that used to be limited to animals and
      human cadavers. The advantages and shortcomings of current computer models are
      discussed. One of the computer models was used to predict the pressures and shear
      stresses developed in the brain and the extent of stretch of the bridging veins
      in the brains of American football players who sustained severe helmet-to-helmet
      head impact during the game. It was found that increases in intracranial pressure
      were more dependent on translational acceleration while the primary determinant
      for the development of shear stresses in the brain is rotational acceleration.
      Although the current head injury criterion is based almost entirely on
      translational acceleration, it is recommended that any new criterion should
      reflect the contribution of both translational and rotational acceleration.

PMID- 11320594
TI  - Bedside invasive monitoring techniques in severe brain-injured patients.
AB  - In patients with severe brain injury, brain edema, elevated intracranial
      pressure, and cerebral ischemia are accountable for a significant morbidity and
      mortality. New invasive methods of monitoring attempt to foresee the
      physiopathological mechanisms responsible for the production of secondary brain
      injuries. The available methods for monitoring severely brain-injured patients,
      their potential usefulness, advantages, and disadvantages are reviewed.

PMID- 11320595
TI  - Cerebral perfusion and blood flow in neurotrauma.
AB  - Post-traumatic cerebral ischemia is associated with a poor prognosis.
      Optimization of cerebral perfusion and blood flow thus plays a key role in
      contemporary head injury management. However, understanding of the
      pathophysiology of severe head injury is required for optimal patient management.
      This article explains the relationships between cerebral blood flow and
      metabolism and summarizes the current understanding of how these parameters can
      be helpful in the treatment of patients with severe head injuries.

PMID- 11320596
TI  - Endothelial cell activation following moderate traumatic brain injury.
AB  - Traumatic brain injury (TBI) initiates a cascade of acute and chronic injury
      responses which include disturbances in the cerebrovasculature that may result in
      the activation of the microvascular endothelial development of a dysfunction
      endothelium. The present study examines endothelial cell (EC) activation in a
      percussion model of moderate TBI. The criteria for endothelial activation used in
      these studies was surface expression of a number of markers collectively termed
      endothelial activation antigens. Temporal induction of the major
      histocompatibility (MHC) class II molecules, E-selectin (CD62E), vascular cell
      adhesion molecule (VACM-1) (CD106) as well as altered expression of
      constitutively expressed intercellular adhesion molecule-1 (ICAM-1) (CD54), the
      glucose transporter protein (glut-1), the transferrin receptor (tfR) (CD71), and
      MHC class I molecules was examined at various times following impact. Induction
      of E-selectin and increased expression of ICAM-1 was seen by 2 h post-impact (PI)
      and was sustained through 24 h PI. Decreased expression of immunologically
      reactive glut-1 and tfR was observed by 2-4 h PI and remained low up to 24 h PI.
      No induction of VCAM-1, MHC class II molecules or altered constitutive expression
      or MHC class I molecules was seen. Changes in EC activation were observed
      predominantly at the site of impact and were diminished temporarily. These
      results indicate that mild concussive injury to the brain results in activation
      of the endothelium.

PMID- 11320597
TI  - Adenosine and neurotrauma: therapeutic perspectives.
AB  - Cerebral ischemia studies demonstrating that stimulation of adenosine A1
      receptors by either endogenously released adenosine or the administration of
      selective receptor agonists causes significant reductions in the morbidity and
      mortality associated with focal or global brain ischemias have triggered interest
      in the potential of purinergic therapies for the treatment of traumatic injuries
      to the brain and spinal cord. Preliminary findings indicate that activation of A1
      adenosine receptors can ameliorate trauma-induced death of central neurons. Other
      avenues of approach include the administration of agents which elevate local
      concentrations of adenosine at injury sites by inhibiting its metabolism to
      inosine by adenosine deaminase, rephosphorylation to adenosine triphosphate by
      adenosine kinase; or re-uptake into adjacent cells. Amplification of the levels
      of endogenously released adenosine in such a 'site and event specific' fashion
      has the advantage of largely restricting the effect of such inhibitors to areas
      of injury-induced adenosine release. Another approach involving purinergic
      therapy has been applied to the problem of respiratory paralysis following high
      spinal cord injuries. In this instance, the adenosine antagonist theophylline has
      been used to enhance residual synaptic drive to spinal respiratory neurons by
      blocking adenosine A1 receptors. Theophylline induced, and maintained,
      hemidiaphragmatic recovery for prolonged periods after C2 spinal cord hemisection
      in rats and may prove to be beneficial in assisting respiration in spinal cord
      injury patients.

PMID- 11320598
TI  - Design and statistical issues in multicenter trials of severe head injury.
AB  - Multicenter clinical trials are the most powerful agent to evaluate new therapies
      in medicine, but have failed to impact traumatic brain injury, in which at least
      20 such trials have been performed, without a positive result. Such trials need
      to be carefully planned, with a run-in period to ensure center compliance.
      Stratification, careful monitoring, adequate sample size, interim analysis and
      adequate numbers of patients per center are all vital requirements for a useful
      outcome in such trials.

PMID- 11320599
TI  - Impaired motor learning and diffuse axonal damage in motor and visual systems of
      the rat following traumatic brain injury.
AB  - Cognitive-motor functioning or motor skill learning is impaired in humans
      following traumatic brain injury. A more complete understanding of the mechanisms
      involved in disorders of motor skill learning is essential for any effective
      rehabilitation. The specific goals of this study were to examine motor learning
      disorders, and their relationship to pathological changes in adult rats with mild
      to moderate closed head injury. Motor learning deficits were determined by
      comparing the ability to complete a series of complex motor learning tasks with
      simple motor activity. The extent of neuronal damage was determined using silver
      impregnation. At all post-injury time points (day 1 to day 14), statistically
      significant deficits were observed in parallel bar traversing, foot placing,
      ladder climbing, and rope climbing. Performance improved with time, but never
      reached control levels. In contrast, no deficits were found in simple motor
      activity skills tested with beam balance and runway traverse. Histologically,
      axonal degeneration was widely distributed in several brain areas that relate to
      motor learning, including the white matter of sensorimotor cortex, corpus
      callosum, striatum, thalamus and cerebellum. Additionally, severely damaged axons
      were observed in the primary visual pathway, including the optic chiasm, optic
      tract, lateral geniculate nuclei, and superior colliculus. These findings suggest
      that motor learning deficits could be detected in mild or moderate brain injury,
      and this deficit could be attributed to a diffuse axonal injury distributed both
      in the motor and the visual systems.

PMID- 11320600
TI  - Gene expression in neurotrauma.
AB  - It has been established that following injury to the central nervous system two
      types of damage take place, the initial insult and the secondary response to
      injury. This review will focus on the secondary molecular aspects of neurotrauma.
      These responses may be either deleterious or have protective effects upon the
      injured cell population. Molecular responses include the regulation of genes
      which change cellular architecture, up-regulate of growth factors, induce
      reparative stress responses, influence apoptosis and regulate the transcriptional
      process. The purpose of this study is to provide the reader with a brief overview
      of some of the molecular mechanisms which are activated following a neurological
      insult.

PMID- 11320601
TI  - Therapeutic implications of fibroblast growth factors in traumatic spinal cord
      injury.
AB  - Neurological damage after acute traumatic spinal cord injury (SCI) results from
      both the primary mechanical injury as well as the subsequent activation of cell
      death cascades mediating delayed tissue damage. Since secondary injury following
      traumatic SCI is a tightly regulated process in which several neurotrophic
      factors seem to be implicated, administration of these proteins has a clinical
      interest. Fibroblast growth factor may be one of the agents to be used for the
      treatment of traumatic SCI.

PMID- 11320602
TI  - Craniocerebral missile injuries.
AB  - Gun shot wounds to the brain are among the most devastating causes of morbidity
      and mortality in the civilian population. The majority of the victims will not
      survive and for a great number of survivors life becomes an uphill battle with
      permanent deficits and complications. While the fundamental surgical care of
      these patients is essentially unchanged, our scientific understanding of the
      pathophysiological changes and the post-injury care of the victims has been
      evolving. The purpose of this article is to provide an overview of the current
      clinical and laboratory advances in understanding and treating gun shot injuries
      to the brain.

PMID- 11320603
TI  - Penetrating head injury: a prospective study of outcomes.
AB  - The purpose of our study was to describe the outcomes of persons with penetrating
      brain injury resulting from a gunshot wound to the head. It is a prospective
      study of 442 patients admitted with gunshot wounds to the head over a 7 year
      period to our University Trauma Center Emergency Department, an urban trauma
      center and an inpatient rehabilitation hospital with a specialized brain injury
      unit. Measures and factors described include initial Glasgow Coma Scale score,
      Revised Trauma Score, the Disability Rating Scale, Functional Independence
      Measure, levels of cognitive functioning, patient demographics, length of stay,
      hospital charges, and discharge disposition. Initially 36% of patients expired in
      or were dead upon arrival to the Emergency Department; 64% of patients survived
      to be admitted for inpatient care. Of those admitted, 41% expired within the
      first 48 h of admission. Fifty-two percent of those admitted had severe injuries,
      7% moderate injuries, and 42% had mild head injuries. Sixty-two percent of the
      survivors were discharged from acute care to private residences. The remaining
      38% were discharged to programs providing varying levels of care depending upon
      their level of functioning and care needs. Patients sustaining severe injuries
      following gunshot wound(s) to the head have high early mortality. Survivors able
      to participate in an inpatient rehabilitation program have good potential for
      functional improvement.

PMID- 11320604
TI  - Complications of head injury.
AB  - Management of head injury is based on two concepts, proper treatment of the acute
      insult and the prevention and treatment of secondary insults. The head injured
      patient is subject to both intracranial and extracranial secondary insults. This
      paper will review complications related to the central nervous system as well as
      the pulmonary, infectious, gastrointestinal, and psychiatric complications
      frequently seen following traumatic brain injury. Complications following head
      trauma lead to significant acute and chronic morbidity and mortality. It is
      essential that clinicians be able to recognize and treat these complications in
      order to more effectively manage head trauma, improve outcome, and care for
      patients.

PMID- 11320605
TI  - Use of sedative and analgesic agents in neurotrauma patients: effects on cerebral
      physiology.
AB  - Sedation and analgesia is used primarily in the intensive care unit (ICU) to
      limit the stress response to critical illness, provide anxiolysis, improve
      ventilatory support, and facilitate adequate ICU care. However, in the
      neurotrauma ICU there are many other reasons for the use of these agents. The
      primary aim is to prevent secondary cerebral damage by maintaining adequate
      cerebral perfusion pressures. This is accomplished in several different ways.
      Controlling intracranial pressure (ICP) and maintaining an adequate mean arterial
      pressure (MAP) is at the cornerstone of this management. Lowering the metabolic
      demands of the brain is also an important consideration as a treatment strategy.
      Analgesic and sedative agents are utilized to prevent undesirable increases in
      ICP and to lower cerebral metabolic demands. Concerns surrounding the use of
      these agents include time to awakening after discontinuation, effect on the
      cerebrovasculature, and the effect on patient outcome. There are many different
      pharmacological agents available, each with their distinct advantages and
      disadvantages. The purpose of this review is to evaluate the pharmacokinetic and
      pharmacological effects of each of these agents when used in neurotrauma
      patients.

PMID- 11320606
TI  - Comparison of neural precursor cell fate in second trimester human brain and
      spinal cord.
AB  - Neural transplantation holds promise for the treatment of traumatic brain and
      spinal cord injury by replacing lost cellular elements as well as repairing
      neural damage. Fetal human stem cells derived from central nervous system (CNS)
      tissue are potential transplantable sources for all cell types found in the
      mature human nervous system including neurons, astrocytes and oligodendroglia.
      Although nearly all areas of the fetal human neuraxis contain undifferentiated
      neural precursor cells, the phenotypic fate of the daughter cells might vary from
      one region to another during a specific developmental period. The purpose of this
      study was to compare the various cell types derived from neural precursors
      cultured from second trimester fetal human brain and spinal cord. To this end,
      brains (n = 8) and spinal cords (n = 8) of 15-24 week fetuses were dissociated
      and grown in culture medium supplemented with epidermal growth factor (EGF),
      basic fibroblast growth factor (FGF) and leukemia inhibitory factor (LIF). The
      proliferating precursor cells from both brain and spinal cord grew as spherical
      masses that were plated on laminin-coated dishes after seven days in culture.
      During the next 5-7 days, the cells that emerged from these spheres were fixed
      and processed for immunocytochemistry. Brain derived spheres gave rise to cells
      expressing antigens specific for neurons (MAP-2ab and neuron specific
      intermediate filaments), astrocytes (GFAP) and oligodendrocytes (A007). In
      contrast, cells that emerged from spinal cord derived spheres were only
      immunoreactive for GFAP. These data suggest that neuroepithelial precursor cells
      from different CNS regions, although similar in their responsiveness to
      proliferative growth factors, might differ in their ability to generate different
      cell types in the adult CNS.

PMID- 11320607
TI  - Biomechanical properties of calvarium prosthesis.
AB  - There are many materials available for the reconstruction of calvarial defects.
      Even though their biomaterial properties are well known, the biomechanical
      properties as part of the calvarium have not been investigated. In this article,
      calvarial implants are reviewed with their historic development into modern
      cranioplasty. Materials for trephined skulls are classified by their category.
      Individual parameters to describe their mechanical properties are collected and
      revealed in detail. The laboratory testing methodology for cranioplasty material
      is introduced to understand each parameter. At last, we discuss an engineering
      technique to look into the implant behavior. Since there is no standard goal for
      the biomechanical and biomaterial point of view for cranioplasty, this article
      suggests the finite element method for evaluation of the implant behavior and the
      degree of damage upon the impact injury.

PMID- 11320608
TI  - Intracranial pressure and surgical decompression for traumatic brain injury:
      biological rationale and protocol for a randomized clinical trial.
AB  - Commonly, severe traumatic brain injury (TBI) patients undergo amputation of
      contused brain; the rationale being that edema in presumed unsalvageable cerebrum
      increases intracranial pressure (ICP). Neuro-critical care expends great effort
      to control ICP and prevent secondary injury. Non-randomized investigations have
      employed hemicraniectomy with duraplasty after developing refractory ICP. We
      undertook a randomized pilot of hemicraniectomy with duraplasty as the initial
      surgery for severe TBI patients. Goals included reduced ICP therapeutic intensity
      and return to the operating room, and improved neurological outcome. Upon
      hospital presentation, the study was to randomize 92 patients with midline shift
      greater than the size of a surgically removable hematoma. One group was to
      receive standardized hemicraniectomy and duraplasty; the other would undergo
      'traditional' craniotomy (with brain amputation at the neurosurgeon's
      discretion). A standardized medical protocol followed. The six-month Glasgow
      Outcome Scale was the primary outcome, with secondary measures including quality
      of life one year after TBI, duration and frequency of elevated ICP, intensive
      care unit (ICU) therapeutic intensity, operating room return, and ICU and
      hospital lengths-of-stay. This article presents the biological rationale and the
      evidence-based standardized protocols of the study and its outcome measures. The
      study has stopped and a phase III outcome trial is being organized.

PMID- 11320609
TI  - Vascular injury in neurotrauma.
AB  - Traumatic vascular lesions can occur after severe or even the most mild of head
      and cervical trauma. The initial evaluation of the injured patient must be
      thorough and the clinical suspicion of vascular injury must be highly suspected
      based on the mechanism of injury. Traumatic vascular injuries can be broadly
      classified into traumatic aneurysms, dissections and occlusions and fistulae of
      the carotid or vertebral arteries. The current management and treatment options
      of each condition are discussed.

PMID- 11320610
TI  - Random tulips.

PMID- 11320611
TI  - Compassion in medicine.

PMID- 11320612
TI  - Case of the Month. Giant multiple intraductal papilloma of the breast: a case
      report and review of the literature.
AB  - A case is described of multiple intraductal papilloma of the breast in a 39 year
      old Micronesian female who presented to our institution with a 2 year history of
      spontaneous bloody nipple discharge with an associated giant cystic breast mass.
      This case report illustrates an unusual presentation of a rare benign breast
      lesion. The clinical, radiographic, and pathologic features of this disease
      process are discussed; the literature is reviewed; and management options are
      discussed.

PMID- 11320613
TI  - DNR orders in the OR.
AB  - Patients with do-not-resuscitate (DNR) orders may elect to have palliative
      surgery. Should DNR orders be automatically suspended in the operating room (OR)?
      This article addresses the following issues: (1) Ethics of DNR orders. (2) The
      American Society of Anesthesiology's Ethical Guidelines for the Anesthesia Care
      of Patients with Do-Not-Resuscitate Orders or Other Directives that Limit
      Treatment. (3) The Statement of the American College of Surgeons on Advance
      Directives by Patients. (4) Current hospital policies regarding perioperative DNR
      policies in Hawaii. (5) Recommendations to improve DNR policies in the OR.

PMID- 11320614
TI  - The Hawaii Diet: ad libitum high carbohydrate, low fat multi-cultural diet for
      the reduction of chronic disease risk factors: obesity, hypertension,
      hypercholesterolemia, and hyperglycemia.
AB  - OBJECTIVE: The purpose of this study was to determine the health effects of a
      high carbohydrate, low fat multi-cultural traditional diet, The Hawaii Diet, fed
      ad libitum to an adult population. METHODS: Twenty-two adults recruited from
      various cultural backgrounds in Hawaii were fed, without calorie or portion size
      restriction, the Hawaii Diet for 21 days. The Hawaii Diet, based on familiar
      traditional foods from different cultures, is high in complex carbohydrate (77%
      of calories), low in fat (12% of calories), and moderate in protein (11% of
      calories). Participants were encouraged to eat to satiety. RESULTS: There was a
      significant weight loss on The Hawaii Diet averaging 10.8 lbs (23.8 kg) (P <
      .0001). Blood pressure was decreased from an average of 136.0/82.7 mm Hg to
      125.5/78.9 mm Hg yielding a significant decrease of 10.4 mm Hg for systolic (P <
      .01). Beginning diastolic levels were normal so decreases in these values were
      not significant. Average lipid values also decreased with total serum cholesterol
      being significantly reduced from 205.3 to 156.9 mg/dl (P < .0001); LDL from 125.9
      to 94.9 mg/dl (P < .001); and HDL from 38.3 to 31.3 mg/dl (P < .0005).
      Triglycerides (238.7 to 152.2 mg/dl) and the Chol:HDL ratio (5.8 to 5.2) improved
      at marginally significant levels (P < .08). There was also a significant
      reduction in blood glucose levels from 112.2 to 91.5 mg/dL (P < .01). CONCLUSION:
      The Hawaii Diet consisting of high carbohydrate, low fat ethnic meals appears to
      have a beneficial influence on weight loss and in decreasing systolic blood
      pressure, total cholesterol, LDL, and blood glucose values. Marginal improvement
      occurred for triglyceride levels. There was also a significant drop in HDL
      levels, however, the Chol:HDL was ratio did not increase. Further studies of
      longer duration with a control group should be conducted to test the
      effectiveness of The Hawaii Diet in maintaining these health benefits over a
      longer period of time.

PMID- 11320615
TI  - Major new grant in cancer epidemiology.

PMID- 11320616
TI  - [Cellular antigen stimulation test (CAST). A new possibility in diagnosis of
      aspirin-sensitivity rhinosinusitis?].

PMID- 11320617
TI  - [Difficult decision in treatment of Meniere disease].

PMID- 11320618
TI  - [Bilateral recurrent laryngeal nerve paralysis].
AB  - This paper seeks to provide the reader with a state-of-the-art review of the
      aetiology, diagnosis and clinical management of bilateral recurrent nerve
      paralysis. The recurrent laryngeal nerves are more frequently involved in
      bilateral paralysis than any other cranial nerve. Most of the underlying lesions
      are iatrogenic, with thyroid surgery being the single most important causative
      factor. However, a variety of different reasons can lead to such a condition.
      Whenever the aetiology is uncertain, a complete diagnostic work-up is mandatory.
      Massive stridor on inspiration is the key symptom. Indirect laryngoscopy confirms
      the diagnosis. Laryngeal electromyography is of great value because it
      differentiates between paralysis and ankylosis of the cricoarytenoid joint.
      Moreover, in many cases, laryngeal electromyography yields reliable prognosis of
      clinical outcome. While unfavorable results can be predicted with high accuracy,
      correct prognosis of complete recovery is more difficult. Clinical management is
      surgical in the vast majority of cases. A variety of endoscopic techniques for
      widening the glottic airway are available today and are discussed in detail.
      Compared to permanent tracheostomy, these procedures have much less impact on the
      patient's quality of life and should be preferred whenever possible. Since such
      an operation is irreversible, a decision should be made only in the presence of a
      reliable electrophysiological prognosis and/or after 6-9 months of watchful
      waiting. Inevitably, voice quality is traded for airway normalisation. However,
      modern surgical techniques accomplish very tolerable phonatory results. Timing,
      type and extent of surgery need to be customised for every patient individually.

PMID- 11320619
TI  - [The value of saccotomy in Meniere disease. A long-term analysis of 42 cases].
AB  - MATERIAL AND METHODS: Saccotomy is well known to be a specific alternative
      treatment for patients suffering from conservatively intractable Meniere's
      disease. In a long-term study, we investigated the results in hearing and vertigo
      after this operation and evaluated the subjective contentment of our patients.
      For the first time, we focused on the influence of an intraoperatively observed
      fibrotic narrowing (11 cases) of the endolymphatic sac ("sac fibrosis") on these
      results. RESULTS: We found complete restitution or significant improvement of the
      typical vertigo attacks after saccotomy in more than 80% of the cases with a
      normally shaped endolymphatic sac as determined microscopically during operation.
      In the cases with sac fibrosis, however, we saw a considerable reduction of this
      percentage to about 36%. Regardless of the presence of sac fibrosis, 50% of our
      patients showed progressive hearing loss in the operated ear after saccotomy. The
      postoperative hearing remained unchanged in about 25% of the cases. The
      contentment of the patients depended mostly on the postoperative vertigo and not
      on the hearing. CONCLUSION: We consider a microscopically normally shaped and
      wide saccus endolymphaticus to be a very important prognostic factor for the
      success of saccotomy. Consequently, preoperative selection of patients with sac
      fibrosis, for example, with high-resolution MRI, appears to be advisable.

PMID- 11320620
TI  - [Dependence of "amplitude modulation following response" on attention].
AB  - BACKGROUND AND OBJECTIVE: Amplitude modulation following responses (AMFR) allows
      good estimation of the hearing threshold due to the very narrow band excitation
      of the cochlea. Audiological use of AMFR requires knowledge of the relationship
      of these responses to the state of vigilance. The few studies published compared
      only qualitatively the amplitude of AMFR recorded in awake subjects to that
      recorded in sleeping subjects. A quantitative determination of the level of
      vigilance on the basis of recorded physiological parameters has not yet been
      carried out. In the present study, the relationship between the amplitude of AMFR
      and the level of vigilance was investigated quantitatively. PATIENTS/METHODS: In
      eight adults with normal hearing, the relationship between the AMFR amplitude and
      EEG amplitude in the delta- and theta-band was determined. The amplitude in both
      frequency bands was used to indicate the state of vigilance. The subjects were
      studied during natural and drug-induced sleep. A 1-kHz carrier tone with a
      sinusoidally modulated amplitude of 40 Hz or 80 Hz was used as stimulus. RESULTS:
      At 40-Hz modulation frequency, the AMFR amplitude correlates with the EEG
      amplitude both in natural and drug-induced sleep. An increase in EEG activity is
      paralleled by a significant reduction of AMFR amplitude. At 80-Hz modulation
      frequency, no relationship between AMFR amplitude and EEG activity could be
      detected. Under all conditions, the amplitudes of AMFR evoked by a modulation
      frequency of 80 Hz were significantly lower than those evoked by 40 Hz.
      CONCLUSIONS: These results suggest that for an audiological use of the 40-Hz AMFR
      the state of vigilance should be stabilised at a constantly high level. In spite
      of the lower influence of vigilance on the 80-Hz AMFR, this response appears less
      ideal for threshold estimation in adults due to the significantly smaller
      amplitudes.

PMID- 11320621
TI  - [Results of an in vitro study and initial clinical application of a combined
      Ho:YAG-/Nd:YAG laser].
AB  - BACKGROUND AND OBJECTIVE: A combined Ho:YAG/Nd:YAG laser produces light with
      properties similar to the beams of the mainly coagulating Nd:YAG laser and the
      cutting CO2 laser alone. PATIENTS/METHODS: The combined laser was tested in vitro
      on pig tissue. Additionally, we used this new combined tool for enoral
      operations. RESULTS: An effect of the pulsed Ho:YAG laser was explosive-like
      tissue disruption and sprinkling of fragments. Simultaneous use of the Nd:YAG
      laser resulted in an enlarged zone of coagulation. Clinically, the laser-assisted
      intervention was inferior to the classic operational methods. CONCLUSIONS:
      Comparing the established CO2 laser and the Ho:YAG laser, the latter showed only
      the advantage of delivery via a flexible fiber. Sprinkling of tissue fragments
      and wide incisions are oncologically problematic. We conclude that this new tool
      is of minor value for otorhinolaryngologists and head and neck surgeons.

PMID- 11320622
TI  - [Treatment of therapy refractory chronic otitis externa by local injection of
      triamcinolone acetate crystalline suspension. Initial experiences].
AB  - BACKGROUND AND OBJECTIVE: External otitis is characterized by otalgia, otorrhea,
      itching, and hearing loss. Treatment usually consists of local application of
      corticosteroids and antibiotics. Chronic external otitis is accompanied by
      thickening of the skin in the external auditory channel. This reduces the effect
      of the applied substances. Local injection of suitable drugs may support the
      conservative treatment. The aim of the study was to evaluate the efficacy of
      local injection of triamcinolone acetonide in the external auditory channel.
      PATIENTS/METHODS: Thirteen patients with external otitis resistant to
      conservative treatment received an injection of triamcinolone acetonide in the
      external auditory channel. The improvement achieved was assessed by clinical
      examination and questionnaires. RESULTS: The symptoms improved substantially in
      all patients; most of the patients were cured completely. CONCLUSIONS: Our
      results demonstrate that local injection of triamcinolone acetonide is effective
      in the management of chronic external otitis.

PMID- 11320623
TI  - [Prognostic significance of expression of p53, bcl-2 and bax in squamous
      epithelial carcinoma of the larynx--a multivariate analysis].
AB  - BACKGROUND AND OBJECTIVE: Conventional clinicopathologic parameters do not
      accurately reflect the clinical outcome of patients with head and neck carcinoma.
      The establishment of additional prognostic factors that may give insight into the
      biologic features of a tumor is therefore an essential goal. The present study
      analyses the expression patterns of p53, bcl-2, and bax with regard to their
      relationships with conventional tumor parameters and to their prognostic
      significance in patients with laryngeal squamous cell carcinoma.
      PATIENTS/METHODS: Paraffin-embedded tissue sections of 88 primary laryngeal
      squamous cell carcinomas diagnosed and treated between 1986 and 1996 were
      investigated for p53, bcl-2, and bax protein expression by immunohistochemistry.
      The mean follow-up time was 45.9 months. RESULTS: Bcl-2 immunoreactivity was
      positively correlated with an advanced clinical stage, a high T category,
      regional lymph node metastasis, and a high histological grading. Significant
      relationship between clinicopathologic parameters and p53 or bax expression were
      not detectable. The age of the patients, advanced disease, positive bcl-2
      expression, and a high level of p53 expression were significantly associated with
      shortened disease-specific survival in univariate analysis. In multivariate
      analysis, age, clinical stage, and p53 expression had independent prognostic
      value. CONCLUSIONS: Although expression of p53 and bcl-2 was found to be
      clinically relevant in univariate analysis, only p53 but not bcl-2 was an
      independent predictor of patient outcome. This superiority of p53 in multivariate
      analysis points to its central role within cell cycle and death regulation, with
      which it influences two important parameters of tumor progression.

PMID- 11320624
TI  - [Siblings with pediatric hearing loss. Data on age at diagnosis and degree of
      hearing loss].
AB  - The Deutsches Zentralregister fur kindliche Horstorungen (DZH = German Registry
      for Hearing Loss in Children) has so far (30.6.2000) entered data records of
      4,027 permanently hearing impaired children. These records include data on a
      total of 151 pairs of siblings. In seven cases a third sibling was registered. An
      analysis of the data of siblings with different dates of birth shows that the
      diagnosis for older siblings was delayed 2 years on average compared to the
      younger siblings (mean 23.6 months, 95% confidence interval 19.3-27.8 months).
      The degree of hearing loss, which crucially determines the average age at which a
      child is diagnosed, correlates statistically significantly with pairs of
      siblings, so that misleading results can be almost totally avoided. In 11 of 17
      cases of twins and triplets, the diagnosis was pronounced simultaneously for both
      siblings; in the remaining 6 cases, one sibling was diagnosed later. It has
      become apparent that younger siblings of hearing-impaired children profit from
      the concomitant routine diagnostic investigation of siblings of hearing-impaired
      children nowadays common in many institutions, but avoidable delays nevertheless
      still occur, as shown by the data for twins and triplets. Since in approximately
      18% of the registered children with one or more siblings one of the brothers or
      sisters is likewise hearing-impaired, consistent family investigation is
      recommended.

PMID- 11320625
TI  - [Arteriovenous fistula of the maxillary artery, eustachian tube dysfunction and
      tinnitus after Le Fort I osteotomy].
AB  - A 36-year-old woman with a maxillary retrognathia underwent a Le Fort I
      osteotomy. Postoperatively, she complained of pulsatile noise and hearing loss in
      the left ear. Carotid arteriography revealed an arteriovenous fistula of the left
      maxillary artery; in addition, a persistent eustachian tube dysfunction with left
      middle ear effusion was noticed. After embolization of the fistula and
      ventilation tube treatment, improved hearing and a significant reduction of
      tinnitus were achieved. Arteriovenous fistulas after orthognathic surgery are
      very rare. Postoperative eustachian tube dysfunction has not yet been reported in
      the literature.

PMID- 11320626
TI  - [Dyspnea caused by spontaneous hematoma of the oropharynx and larynx during
      marcumar therapy].
AB  - A patient with a history of tachycardiac atrial fibrillation and pulmonary
      embolism was admitted to the emergency unit with acute shortness of breath. The
      patient was on coumarin medication. Pulmonary embolism, heart failure, or
      pulmonary edema could be ruled out. Laryngoscopy revealed a huge hematoma of both
      valleculae extending to the lateral pharyngeal wall and the epiglottis. The
      epiglottic cartilage was displaced to the posterior pharyngeal wall. The INR was
      > 6. Prothrombin complex, vitamin K1, corticoids, and fresh frozen plasma were
      administered immediately. The patient was monitored--without tracheotomy--in the
      intensive care unit and received oxygen. In a patient with dyspnea, impaired
      ventilation has to be considered besides impaired perfusion or diffusion.

PMID- 11320627
TI  - [Underestimation of minor noise-induced hearing loss].

PMID- 11320628
TI  - [Pulsating space-occupying lesion of the right tympanum after radical operation.
      Glomus jugulare tumor and acoustic neuroma right].

PMID- 11320629
TI  - [International health market within the European community. New chances for
      patients and health care providers].

PMID- 11320630
TI  - [Diagnostic and therapeutic possibilities in temporomandibular joint diseases].

PMID- 11320631
TI  - Ergometry for estimation of mechanical power output in sprinting in humans using
      a newly developed self-driven treadmill.
AB  - An evaluation of mechanical power during walking and running in humans was
      undertaken after developing a specially designed running ergometer (RE) in which
      the subjects gripped the handlebar in front of them keeping both arms straight
      and in a horizontal position. Ten subjects participated in comparisons of the
      mean horizontal pushing force (MFam) on the handlebar with the mean horizontal
      ground reaction force (MFfp) recorded by force platform under the RE during five
      different constant speeds of walking or running and sprint running with maximal
      effort. Mechanical power developed during sprint running on the RE was compared
      with a 50 m sprint. Mean linear velocity (Mv) of the RE belt was recorded by the
      rotary encoder attached to the axis of the belt. Mean mechanical power calculated
      from the handlebar setting (MPam = MFam x Mv) was compared to that calculated
      from force platform recordings (MPfp = MFfp x Mv). A high test-retest
      reproducibility was observed for both MFfp (r = 0.889) and MFam (r = 0.783).
      Larger values for the coefficient of variation for MFam (11.3%-15.8%) were
      observed than for MFfp (3.3%-8.2%). The MPam, which were obtained from five
      different constant speeds of walking, running and sprint running were closely
      correlated to those of MPfp (y = 0.98x - 19.10, r = 0.982, P < 0.001). In sprint
      running, MPam was 521.7 W (7.67 W.kg-1) and was correlated to the 50 m sprint
      time (r = -0.683, P < 0.01). It is concluded that the newly developed RE was
      useful in the estimation of mechanical power output during human locomotion such
      as when walking, jogging and sprinting.

PMID- 11320632
TI  - Assessment of lower-back muscle fatigue using electromyography, mechanomyography,
      and near-infrared spectroscopy.
AB  - We have investigated the etiology of lower-back muscle fatigue using simultaneous
      recordings of electromyography (EMG), mechanomyography (MMG), and near-infrared
      spectroscopy (NIRS) in an attempt to shed some light on the electrophysiological,
      mechanical, and metabolic characteristics, respectively. Eight male subjects
      performed isometric back extensions at an angle of 15 degrees with reference to
      the horizontal plane, for a period of 60 s. Surface EMG, MMG and NIRS signals
      were recorded simultaneously from the center of the erector spinae at the level
      of L3. NIRS was measured to determine the level of muscle blood volume (BV) and
      oxygenation (Oxy-Hb). The root mean square amplitude value (RMS) of the EMG
      signal was significantly increased at the initial phase of contraction and then
      fell significantly, while mean power frequency (MPF) of the EMG signal decreased
      significantly and progressively as a function of time. There were also
      significant initial increases in RMS-MMG that were followed by progressive
      decreases at the end of fatiguing contractions. MPF-MMG remained unchanged.
      Muscle BV and Oxy-Hb decreased dramatically at the onset of the contraction and
      then remained almost constant throughout the rest of the contraction. These
      results, obtained by simultaneous recordings of EMG, MMG, and NIRS, demonstrate
      that the restriction of blood flow due to high intramuscular mechanical pressure
      is one of the most important factors in muscle fatigue in the lower-back muscles.
      In addition, the simultaneous recording system described here can be used to
      obtain more reliable information regarding the mechanism(s) of lower-back muscle
      fatigue.

PMID- 11320633
TI  - Markers of inflammation and myofibrillar proteins following eccentric exercise in
      humans.
AB  - The purpose of this study was to examine the time-course and relationships of
      technetium-99m (99mTc) neutrophils in muscle, interleukin-6 (IL-6), myosin heavy
      chain fragments (MHC), eccentric torque, and delayed onset muscle soreness (DOMS)
      following eccentric exercise in humans. Twelve male subjects completed a pre-test
      DOMS questionnaire, performed a strength test and had 100 ml blood withdrawn for
      analysis of plasma IL-6 and MHC content. The neutrophils were separated, labelled
      with 99mTc, and re-infused into the subjects immediately before the exercise.
      Following 300 eccentric repetitions of the right quadriceps muscles on an
      isokinetic dynamometer, the subjects had 10 ml of blood withdrawn with repeated
      the eccentric torque exercise tests and DOMS questionnaire at 0, 2, 4, 6, 20, 24,
      48, 72 h, and 6 and 9 days. Bilateral images of the quadriceps muscles were taken
      at 2, 4, and 6 h. Computer analysis of regions of interest was used to determine
      the average count per pixel. The 99mTc neutrophils and IL-6 increased up to 6 h
      post-exercise (P < 0.05). The neutrophils were greater in the exercised muscle
      than the non-exercised muscle (P < 0.01). The DOMS was increased from 0 to 48 h,
      eccentric torque decreased from 2 to 24 h, and MHC peaked at 72 h post-exercise
      (P < 0.001). Significant relationships were found between IL-6 and 2 h and DOMS
      at 24 h post-exercise (r = 0.68) and assessment of the magnitude of change
      between IL-6 and MHC (r = 0.66). These findings suggest a relationship between
      damage to the contractile proteins and inflammation, and that DOMS is associated
      with inflammation but not with muscle damage.

PMID- 11320634
TI  - Post-exercise recovery of autonomic cardiovascular control: a study by spectrum
      and cross-spectrum analysis in humans.
AB  - The recovery of the baseline autonomic control of cardiovascular activity after
      exercise has not been extensively studied. In 12 healthy subjects, we assessed
      the time-course of recovery by autoregressive spectrum and cross-spectrum
      analysis of heart period and systolic blood pressure during the 3 h after the end
      of 20 min of steady-state exercise at 50% (light workload, LW) and 80% (moderate
      workload, MW) of the individual's anaerobic threshold. The electrocardiogram and
      non-invasive blood pressure were simultaneously recorded during 10 min periods in
      the sitting position, at rest before exercise, and at 15, 60 and 180 min of
      recovery after exercise. At 15 min we observed a persistent tachycardia and
      relative hypotension; after MW, at 60 min heart rate was still slightly higher.
      Spectrum and cross-spectrum analysis showed, at 15 min, an increase in the low
      frequency component of systolic blood pressure, a reduction in the high frequency
      component of heart rate (larger in MW), and a decrease in baroreceptor
      sensitivity. After 60 and 180 min none of these parameters was significantly
      different from those at rest, although, in MW, some subjects still displayed
      signs of sympathetic activation after 1 h. We concluded that, after 15 min of
      recovery, the cardiovascular reflexes were blunted, that sympathetic nerve
      activity was still enhanced, and that the tone in the vagus had not fully
      recovered. Only the persistent vagal restraint seemed to be exercise intensity
      dependent. For complete restoration of autonomic control after LW 1 h of rest was
      sufficient, and just enough after MW.

PMID- 11320635
TI  - Neutrophil antiserum response to decrease in proteolytic activity in loaded rat
      muscle.
AB  - The leukocytes that are found in skeletal muscles after intense muscular activity
      have been shown to infiltrate areas of injury in skeletal muscle tissue. We
      believe that leukocyte enzymes, which appear in the tissue after the
      degranulation or destruction of leukocytes, could play a role in tissue enzyme
      activities. Neutrophil proteinases were investigated. Histological data provided
      evidence of rat muscular tissue infiltration by leukocytes after intense physical
      loading. To reduce the influx of leukocytes in rat muscles, a rabbit antiserum
      against rat peritoneal leukocytes was injected into rats after muscle loading.
      This resulted in a reduction in muscle cytosol proteolytic activity as compared
      to control animals (who received saline injections). The levels of proteolytic
      activities of media conditioned by the soleus muscle isolated from antiserum
      treated rats were also reduced. These data provide evidence that the increase in
      proteolytic activity observed in rat skeletal muscles after physical loading is
      partially induced by neutrophil proteinases.

PMID- 11320636
TI  - Influence of body mass on maximal oxygen uptake: effect of sample size.
AB  - Basal metabolic rate is scaled to body mass to the power of 0.73, and we
      evaluated whether a similar scaling applies when the O2 transport capacity of the
      body is challenged during maximal exercise (i.e. at maximal O2 uptake, VO2max).
      The allometric relationship between VO2max and body mass (y = a.xb, where y is
      VO2max and x is body mass) was developed for 967 athletes representing 25
      different sports, with up to 157 participants in each sport. With an increasing
      number of observations, the exponent approached 0.73, while for ventilation the
      exponent was only 0.55. By using the 0.73 exponent for VO2max, the highest value
      [mean (SD)] for the males was obtained for the runners and cyclists [234 (16)
      ml.kg-0.73.min-1], and for the females the highest value was found for the
      runners [189 (14) ml.kg-0.73.min-1]. For the females, aerobic power was about 80%
      of the value achieved by the males. Scaling may help both in understanding
      variation in aerobic power and in defining the physiological limitations of work
      capacity.

PMID- 11320637
TI  - Contraction-specific differences in maximal muscle power during stretch
      shortening cycle movements in elderly males and females.
AB  - Elderly people (age 75 years; n = 48 males and 34 females) were studied in order
      to elucidate gender differences in elderly subjects on the determinants of muscle
      power (force and velocity) during a stretch-shortening cycle. All subjects
      performed three maximal counter-movement vertical jumps using both legs, on a
      force platform (Kistler 9281 B). The eccentric (Ep) and concentric (Cp) phases of
      the jumps were analyzed. The Ep was further divided into an acceleration phase
      (Epacc: from the start of the downward movement to the maximal negative velocity)
      and deceleration phase (Epdec: from the maximal negative velocity to the end of
      the downward movement). Jump height for the men was higher than for the women (P
      < 0.001). During both Epacc and Epdec no significant differences were observed
      between males and females in force and power generation. However, the men had a
      higher peak muscle power during the Cp, which may be explained exclusively by the
      velocity determinant (P < 0.001). No specific gender-related strategy appeared to
      influence the motor pattern of the movement. The comparable eccentric force
      generation of the leg extensors in both genders suggests a similar ability to
      cope with eccentric muscle actions during everyday activities. In contrast, the
      marked lower capacity for concentric contractions in women may result in an
      impaired performance, especially in activities where intense and rapid movements
      are essential, for example when reversing a forward fall. This may be one reason
      why elderly women are more prone to falls than are elderly men.

PMID- 11320638
TI  - Motor impairment in the human hand following eccentric exercise.
AB  - Motor impairment was induced by having subjects perform two sets of 50 maximal
      contractions, using the first dorsal interosseus (FDI) muscle to abduct the index
      finger, while the muscle was being stretched. Tests were conducted prior to the
      exercise (pre-exercise) and 24 h following the exercise (post-exercise). There
      were declines of 19% in maximal abduction torque and 15% in maximal flexion
      torque at the metacarpaphalangeal joint, during isometric contraction post
      exercise compared to pre-exercise. The ability to stabilize the
      metacarpophalangeal joint about the abduction/adduction axis was reduced by 14%
      post-exercise, and the variability in tracking an isometric torque target
      increased by 30%. There was a decrement of 7%-10% in the median frequency of the
      power density spectrum of FDI electromyogram (EMG) throughout a 60 s maintained
      abduction at 50% maximal voluntary contraction. The mean rectified EMG, on the
      other hand, increased by 100%-175% for torque levels below 40% of maximal
      voluntary contraction, post-exercise. The results were consistent with
      preferential injury of type II muscle fibres in FDI. Although non-exercised
      synergist muscles appeared to be inhibited during maximal voluntary flexion,
      there was evidence that they compensated for injured FDI muscle fibres during
      maintained contraction at sub-maximal flexion torque.

PMID- 11320639
TI  - The effects of voluntary contraction intensity and gender on perceived exertion
      during isokinetic quadriceps exercise.
AB  - The objectives of the present study were to: (1) examine perceived exertion
      across different target voluntary contraction intensities, (2) compare perceived
      exertion ratings with actual target intensities, and (3) compare perceived
      exertion ratings between males and females. The subjects for this study included
      30 healthy, college-aged male (n = 15) and female (n = 15) volunteers. All
      subjects were free of orthopedic, cardiopulmonary, systemic and neurological
      disease. Each subject completed five maximal isokinetic, concentric quadriceps
      contractions in a seated position at 60 degrees.s-1 to determine their single,
      highest peak torque. All subjects then completed, in a random order, 3-5
      submaximal isokinetic contractions at 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, and
      90% of their single, highest peak torque. Each relative contraction level (i.e.,
      percentage) was achieved by having the subjects attempt to match the peak of
      their torque curve to a horizontal line on a computer monitor. Perceived exertion
      was measured by asking the subjects to provide a number that corresponded to the
      feelings in their quadriceps during exercise by viewing a modified category-ratio
      (CR-10) scale. The results of a two-factor (gender x intensity) analysis of
      variance revealed a significant, intensity main effect (F8,232 = 92.19, P <
      0.001, eta 2 = 0.77, 1 - beta = 0.99) and no significant gender main effect
      (F8,232 = 2.66, P = 0.11, eta 2 = 0.09, 1 - beta = 0.35) or interactions (F8,232
      = 1.01, P = 0.43, eta 2 = 0.04, 1 - beta = 0.46). The findings of this study
      demonstrate that perceived exertion is significantly (P < 0.05) different from
      the specific target values on the CR-10 scale at 10%, and 50-90% maximum
      voluntary contraction. The results revealed that the increase in perceived
      exertion across the contraction intensities could be fit to both linear (F1,29 =
      205.41, P < 0.001, eta 2 = 0.88, 1 - beta = 0.99) and quadratic (F1,29 = 10.05, P
      = 0.004, eta 2 = 0.26, 1 - beta = 0.87) trends. These findings suggest that
      perceived exertion is underestimated during submaximal isokinetic exercise, and
      is not different between males and females.

PMID- 11320640
TI  - Force/velocity and power/velocity relationships in squat exercise.
AB  - The purpose of this study was to describe the force/velocity and power/velocity
      relationships obtained during squat exercise. The maximal force (F0) was
      extrapolated from the force/velocity relationship and compared to the isometric
      force directly measured with the aid of a force platform placed under the
      subject's feet. Fifteen international downhill skiers [mean (SD) age 22.4 (2.6)
      years, height 178 (6.34) cm and body mass 81.3 (7.70) kg] performed maximal
      dynamic and isometric squat exercises on a guided barbell. The dynamic squats
      were performed with masses ranging from 60 to 180 kg, which were placed on the
      shoulders. The force produced during the squat exercise was linearly related to
      the velocity in each subject (r2 = 0.83-0.98, P < 0.05-0.0001). The extrapolated
      F0 was 23% higher than the measured isometric force (P < 0.001), and the two
      measurements were not correlated. This may be attributed to the position of the
      subject, since the isometric force was obtained at a constant angle (90 degrees
      of knee flexion), whereas the dynamic forces were measured through a range of
      movements (from 90 degrees to 180 degrees). The power/velocity relationship was
      parabolic in shape for each subject (r2 = 0.94-0.99, P < 0.01-0.0001). However,
      the curve obtained exhibited only an ascending part. The highest power was
      produced against the lightest load (i.e., 60 kg). The maximal power (Wmax) and
      optimal velocity were never reached. The failure to observe the descending part
      of the power/velocity curve may be attributed to the upper limitation of the
      velocities studied. Nevertheless, the extrapolation of Wmax from the
      power/velocity equation showed that it would be reached for a load close to body
      mass, or even under unloaded conditions.

PMID- 11320641
TI  - Effect of high altitude (7,620 m) exposure on glutathione and related metabolism
      in rats.
AB  - Reduced and oxidised glutathione (GSH and GSSG) contents, and glutathione
      reductase, and glutathione S-transferase activities were studied in the livers,
      muscles, and blood/erythrocytes of male Sprague-Dawley rats exposed to
      intermittent hypoxia (6 h.day-1) at a simulated altitude of 7,620 m for 1, 7, 14,
      and 21 days. Significant decreases in GSH and increases in GSSG contents were
      observed in the muscles and blood of hypoxia-exposed rats in comparison to
      unexposed rats. Significant declines in GSH content by 43% and 45% respectively
      in muscles and blood were observed in the group exposed for 1 day which tended to
      recover on subsequent exposure. Glutathione reductase and glutathione S
      transferase activities were decreased in the livers and erythrocytes of hypoxia
      exposed rats, but were increased significantly in muscle. Lipid peroxidation was
      also increased in the livers and muscles of exposed rats. The changes were
      indicative of an increased production of reactive oxygen species and an
      impairment of drug and xenobiotic metabolism during exposure to high altitude
      hypoxia.

PMID- 11320642
TI  - Effect of creatine supplementation on metabolism and performance in humans during
      intermittent sprint cycling.
AB  - This double blind study investigated the effect of oral creatine supplementation
      (CrS) on 4 x 20 s of maximal sprinting on an air-braked cycle ergometer. Each
      sprint was separated by 20 s of recovery. A group of 16 triathletes [mean age
      26.6 (SD 5.1) years. mean body mass 77.0 (SD 5.8) kg, mean body fat 12.9 (SD
      4.6)%, maximal oxygen uptake 4.86 (SD 0.7) l.min-1] performed an initial 4 x 20 s
      trial after a muscle biopsy sample had been taken at rest. The subjects were then
      matched on their total intramuscular creatine content (TCr) before being randomly
      assigned to groups to take by mouth either a creatine supplement (CRE) or a
      placebo (CON) before a second 4 x 20 s trial. A muscle biopsy sample was also
      taken immediately before this second trial. The CrS of 100 g comprised 4 x 5 g
      for 5 days. The initial mean TCr were 112.5 (SD 8.7) and 112.5 (SD 10.7) mmol.kg
      1 dry mass for CRE and CON, respectively. After creatine loading and placebo
      ingestion respectively, CRE [128.7 (SD 11.8) mmol.kg-1 dry mass] had a greater (P
      = 0.01) TCr than CON [112.0 (SD 10.0) mmol.kg-1 dry mass]. While the increase in
      free creatine for CRE was statistically significant (P = 0.034), this was not so
      for the changes in phosphocreatine content [trial 1: 75.7 (SD 6.9), trial 2: 84.7
      (SD 11.0) mmol.kg-1 dry mass, P = 0.091]. There were no significant differences
      between CRE and CON for citrate synthase activity (P = 0.163). There was a
      tendency towards improved performance in terms of 1 s peak power (in watts P =
      0.07; in watts per kilogram P = 0.05), 5 s peak power (in watts P = 0.08) and
      fatigue index (P = 0.08) after CrS for sprint 1 of the second trial. However,
      there was no improvement for mean power (in watts P = 0.15; in watts per kilogram
      P = 0.1) in sprint 1 or for any performance values in subsequent sprints. Our
      results suggest that, while CrS elevates the intramuscular stores of free
      creatine, this does not have an ergogenic effect on 4 x 20 s all-out cycle
      sprints with intervening 20-s rest periods.

PMID- 11320643
TI  - Chemokines are elevated in plasma after strenuous exercise in humans.
AB  - During the last few years much attention has been paid to the chemokines.
      Chemokine receptors are necessary to render a target permissive for infection by
      the human immunodeficiency virus (HIV) and high concentrations of chemokines have
      been shown to protect against the progression of HIV disease towards death. In
      the present study, we investigated the capability of strenuous exercise to induce
      elevated plasma concentrations of the chemokines interleukin (IL)-8, macrophage
      inflammatory protein (MIP)-1 alpha and MIP-1 beta. Eight male athletes completed
      the Copenhagen Marathon 1997. Blood was sampled before, immediately after the run
      and every 30 min during a 4 h recovery period. Plasma chemokine concentrations
      were measured using enzyme-linked immunosorbent assays. The IL-8, MIP-1 alpha and
      MIP-1 beta concentrations all peaked 0.5 h after the run when they were 6.7-fold,
      3.5-fold and 4.1-fold increased, respectively. The elevated concentrations of
      chemokines in plasma after exercise could have implications for HIV-infected
      individuals; a possibility that needs further investigation.

PMID- 11320644
TI  - Age related blood flow around the Achilles tendon during exercise in humans.
AB  - Injuries due to the overuse of tendons increase with age, and it has been
      suggested that this correlates with hypovascularity of the tendon. In the present
      study, the peritendinous blood flow was determined using xenon-133 washout at
      rest and during standardised intermittent exercise of the calf-muscle (1.5 s
      contraction, 1.5 s rest, 40 min) in young (n = 6; 26 years), middle-aged (n = 6;
      48 years), and older (n = 6; 74 years) individuals. At rest, the older
      individuals had a lower peritendinous blood flow compared with the two other age
      groups. During exercise, blood flow in all three groups rose 2.5-3.5-fold to
      reveal similar blood flows [2.7 (SEM 0.5) to 7.8 (SEM 1.0) ml.100 g tissue-1 min
      1 (young group); 3.0 (SEM 0.4) to 7.3 (SEM 1.6) ml.100 g tissue-1 min-1 (middle
      aged group); 1.6 (SEM 0.2) to 5.5 (SEM 1.1) ml 100 g tissue-1.min-1 (older
      group)]. The findings demonstrated that the peritendinous blood flow to the zone
      of the tendon with the highest incidence of injury from overuse is unaltered by
      age during exercise, and indicates that factors other than blood flow are
      important for the increased incidence with age of injuries from overuse.

PMID- 11320645
TI  - Time of day effects on isometric and isokinetic torque developed during elbow
      flexion in humans.
AB  - The aim of this study was, firstly, to confirm or refute the existence of
      circadian rhythms during several velocities of concentric action of the elbow
      flexor muscles and, secondly, to compare the characteristics of these circadian
      rhythms with those obtained during isometric actions. Eight volunteer subjects
      participated in this study. The circadian rhythms were obtained from six test
      sessions (TS) carried out at different times of day over 6 days with only one TS
      a day. During each TS, oral temperature and the torque of the muscle action were
      measured. The subjects made, on an isokinetic ergometer, two maximal isokinetic
      concentric elbow flexions at five angular velocities (60, 120, 180, 240 and 300
      degrees.s-1) and at an angle of 60 degrees. Torque-angular velocity
      relationships, which characterised the functioning of the muscle during
      concentric and isometric actions, were established for the different times of
      day. The values of the torque recorded at each of the angular velocities
      presented a clear circadian rhythm. After normalisation of the torque values, no
      significant differences were observed among the computed characteristics of the
      circadian rhythms obtained at different angular velocities. Since the circadian
      rhythms during isometric and concentric torque were the same, the characteristics
      of the circadian rhythms of the musculo-skeletal system can be studied using
      either type of muscle action. The results indicated that torque and temperature
      varied concomitantly during the day. Thus, the recording of body temperature
      allows one to estimate the times of occurrence of maximal and minimal values in
      the circadian rhythm of muscle torque.

PMID- 11320646
TI  - Regional and cellular expression of the mannose receptor in the post-natal
      developing mouse brain.
AB  - The mannose receptor, a glycoprotein expressed in a soluble and membrane form by
      macrophages, plays an important role in homeostasis and immunity. Using
      biochemical and immunohistochemical analyses, we demonstrate that this receptor,
      both in its soluble and membrane forms, is expressed in vivo in the post-natal
      murine brain and that its expression is developmentally regulated. Its expression
      is at its highest in the first week of life and dramatically decreases
      thereafter, being maintained at a low level throughout adulthood. The receptor is
      present in most brain regions at an early post-natal age, the site of the most
      intense expression being the meninges followed by the cerebral cortex, brain stem
      and the cerebellum. With age, expression of the mannose receptor is maintained in
      regions such as the cerebral cortex and the brain stem, whereas it disappears
      from others such as the hippocampus or the striatum. In healthy brain, no
      expression can be detected in oligodendrocytes, ependymal cells, endothelial
      cells or parenchymal microglia. The mannose receptor is expressed by perivascular
      macrophages/microglia and meningeal macrophages, where it might be important for
      the brain immune defence, and by two populations of endogenous brain cells,
      astrocytes and neurons. The developmentally dependent, regionally regulated
      expression of the mannose receptor in glial and neuronal cells strongly suggests
      that this receptor plays an important role in homeostasis during brain
      development and/or neuronal function.

PMID- 11320647
TI  - Neurochemically distinct myenteric neurone populations containing calbindin have
      specific distribution patterns around the circumference of the gastric corpus.
AB  - We recently described calbindin immunoreactivity in the myenteric plexus of the
      guinea-pig stomach. To study the neurochemical coding of calbindin D28 k (CALB)
      containing myenteric neurones, the presence of calretinin (CALRET), choline
      acetyltransferase (ChAT), enkephalin (ENK), neuropeptide Y, serotonin (5-HT),
      somatostatin (SOM) and substance P(SP) was investigated immunohistochemically in
      colchicine-treated preparations. Nitric oxide synthase-containing neurones were
      detected by NADPH-diaphorase histochemistry. In addition, we investigated the
      neurone distribution patterns around the gastric corpus. Most CALB neurones were
      ChAT positive. ChAT/CALB neurones were either CALRET (ca 75%) or 5-HT positive
      and most contained in addition SP and/or ENK. All 5-HT neurones contained CALB.
      CALB labelled on average 2.3, 4.8 and 7.5 neurones per ganglion at the lesser
      curvature, in the central region and the greater curvature, respectively, which
      indicated a preferential localisation at the greater curvature. Compared to the
      total number of myenteric neurones, the proportion of CALB neurones increased
      significantly from the lesser curvature (6%) towards the greater curvature (18%).
      This shift, although observed for most ChAT/CALB-positive populations, was most
      prominent for the ChAT/CALB/CALRET/SP/ENK-encoded neurones. SOM-positive and ChAT
      only encoded neurones were preferentially located at the lesser curvature. The
      remaining ten neurochemically defined populations did not exhibit an uneven
      distribution. The colocalisation of CALB with CALRET or 5-HT is specific for
      myenteric neurones in the stomach and represents one significant difference to
      the neurochemical code of CALB neurones in the guinea-pig intestine. The
      functional significance of the unevenness of neurone distribution along the
      circumference of the gastric corpus remains to be studied.

PMID- 11320648
TI  - Role of reactive nitrogen species in neuronal cell damage during intestinal
      schistosomiasis.
AB  - Free radicals are known to be involved in the host reaction during Schistosoma
      mansoni-induced inflammation in the liver and the intestine. In the present
      study, the influence of reactive nitrogen species (RNS) on the enteric neurons of
      infected ileum of mice was investigated. Cryosections and whole-mounts of the
      ileum of control, and 8- and 15-week-infected mice were processed for
      immunohistochemical localization of 3-nitrotyrosine, a biomarker of RNS, and of
      active caspase-3, a key executioner of apoptosis. An antibody directed against
      protein gene product 9.5 or S100 protein was used as a marker for neurons or
      enteroglial cells. In infected mice, but not in control animals, 3-nitrotyrosine
      was detected in parasite eggs and, as revealed by double immunolabelling, in some
      neuronal and enteroglial cells. Quantitative analysis of whole-mounts showed that
      the percentage of 3-nitrotyrosine-immunoreactive neurons significantly increased
      with time in both the submucous and myenteric plexus. Caspase-3 immunoreactivity
      was predominantly found in parasite eggs in infected mice. Immunoreactive enteric
      neurons were occasionally observed. The results indicate that inflammation
      induced RNS are present in the ileum of S. mansoni-infected mice, and participate
      in the elimination of the schistosome eggs causing damage in a significant number
      of enteric neurons. However, neuronal cell death appears to be a rare phenomenon
      in the schistosome-infected mouse ileum.

PMID- 11320649
TI  - Expression and cell-specific and membrane-specific localization of NHE-3 in the
      human and guinea pig upper gastrointestinal tract.
AB  - Na+/H+ exchangers (NHEs) are vital transmembrane transport proteins mediating the
      electroneutral exchange of Na+ and H+ ions in mammalian cells. In the epithelium
      of the lower intestine, the isoform NHE-3 is apparently involved in Na+
      absorption; however, its presence and cellular localization in the duodenum and
      particularly in the stomach remain largely unclear. Therefore, we studied the
      human and guinea pig stomach and duodenum for the expression, regional and
      mucosal distribution pattern, and membrane-specific localization of NHE-3.
      Reverse transcription/polymerase chain reaction analyses revealed strong
      expression of NHE-3 in the stomach and duodenum, where it was identified as a 85
      kDa immunoreactive protein by Western blotting experiments. Whereas NHE-3 was
      localized to the basolateral membrane of surface mucous cells of the stomach, it
      was exclusively confined to the brush border membrane of epithelial cells in the
      duodenum. We conclude that the basolateral NHE-3 in the stomach protects the
      mucosa by secreting protons that diffuse into the mucous cells. In the duodenum,
      the localization of NHE-3 to the apical membrane of enterocytes suggests a
      resorptive function by directional Na+ transport. These findings indicate that
      NHE-3 may be involved in various segment-specific functions in the upper
      gastrointestinal tract.

PMID- 11320651
TI  - Mitochondria-rich cells in gills and skin of an African lungfish, Protopterus
      annectens.
AB  - We used scanning electron microscopy, the vital dye DASPEI and an antibody to the
      inner mitochondrial membrane to study the presence and localisation of
      mitochondria-rich cells in the gills and skin (opercular, dorsal and ventral) of
      the lungfish Protopterus annectens in its free-swimming conditions and at the
      beginning of aestivation. In the free-swimming period, the gills were short and
      thick and the pavement cells were extremely large (30-40 microns). The
      mitochondria-rich cells, which were distributed in the secondary and primary
      epithelium, occurred as two morphologically different types, i.e. elongated and
      oval, similar to the alpha and beta chloride cells of fresh water teleosts. In
      the skin, only one type of mitochondria-rich cells was found, resembling the
      alpha chloride cells. All the mitochondria-rich cells distributed in the gills
      and skin were labelled with anti Ca(2+)-ATPase serum indicating the possible
      uptake of Ca2+ at freshwater chloride cell level. At the start of aestivation,
      the skin and gills were covered by a thick layer of mucus and the epithelium of
      the gills was reduced. The mitochondria-rich cells were almost completely covered
      by the pavement cells.

PMID- 11320650
TI  - TrkA and TrkC neurotrophin receptor-like proteins in the lizard gut.
AB  - The tyrosine kinase proteins (Trk), encoded by the trk family of proto-oncogenes,
      mediate, in mammals, the action of neurotrophins, a family of growth factors
      acting on the development and maintenance of the nervous system. Neurotrophins
      and their specific receptors, TrkA, TrkB and TrkC, seem to be phylogenetically
      well preserved but, in reptiles, data regarding the occurrence of Trk-like
      proteins are very scarce, especially in non-nervous organs. Western blot analysis
      demonstrated that the lizard gut contains TrkA- and TrkC-like, but not TrkB-like,
      proteins. Consistently, TrkA- and TrkC-like immunoreactivity were both observed
      in neurons of the anterior intestine, whereas endocrine cells of the stomach and
      anterior intestine only displayed TrkA-like immunoreactivity. These results
      demonstrate for the first time the occurrence of Trk-like proteins in non
      neuronal tissues of reptilians and provide further evidence for the evolutionary
      preservation of the molecular mass and cell distribution of Trk neurotrophin
      receptor-like proteins in the gut of vertebrates.

PMID- 11320652
TI  - Expression of cathepsin K mRNA and protein in odontoclasts after experimental
      tooth movement in the mouse maxilla by in situ hybridization and immunoelectron
      microscopy.
AB  - This study demonstrated the simultaneous expression of cathepsin K (CK) mRNA by
      in situ hybridization and CK protein by immunoelectron microscopy in odontoclasts
      in mouse maxillae after experimental tooth movement. On the pressure side (the
      area under pressure during tooth movement), CK mRNA was detected in odontoclasts
      in resorption lacunae in the tooth root, in osteoclasts in bone resorption
      lacuane, and in fibroblasts in the periodontal ligament. Using electron
      microscopy, CK protein was detected at the apex of odontoclasts, intracellularly
      in vesicles and granules, and extracellularly in irregularly shaped vacuoles
      (extracellular spaces), on the plasma membrane of the ruffled border, and on and
      between typical striated type I collagen fibrils in the lacunae. These vesicles
      and granules appeared to fuse with irregular vacuoles containing CK-positive
      fragmented fibril-like structures close to the ruffled border. In the basolateral
      portion of odontoclasts, small amounts of CK-positive rough endoplasmic reticulum
      (ER) were found. CK-positive intracellular vacuoles (not extracellular spaces)
      also appeared to fuse with the vesicles and granules. However, these fused
      organelles rarely contained fragmented fibril-like structures. They are probably
      endolysosomes. The distribution of CK in odontoclasts was similar to that
      previously seen in osteoclasts. Furthermore, CK-positive fibril-like structures
      were found in the vacuoles of fibroblasts. These results indicated that during
      tooth movement CK is synthesized in odontoclasts on the pressure side and
      secreted into the tooth resorption lacunae. Therefore, CK may take part in the
      degradation of the dentin matrix (type I collagen fibrils and non-collagenous
      protein) of the tooth root, and in the subsequent intracellular degradation of
      endocytosed fragmented fibril-like structures in endolysosomes.

PMID- 11320653
TI  - ID gene expression varies with lineage during differentiation of pluripotential
      male germ cell tumor cell lines.
AB  - Human male germ cell tumors (GCTs) comprise an excellent model system for
      understanding the molecular events controlling cellular differentiation and
      lineage decision. Pluripotential embryonal carcinoma cell lines derived from GCTs
      can be induced to undergo terminal differentiation along specific lineages
      dependent upon the differentiating agent. We report here that one such cell line,
      NTera2/clone D1 (NT2/D1), previously shown to undergo differentiation along a
      neuronal lineage by all-trans-retinoic acid (RA), can be induced along a distinct
      non-neuronal lineage by the mammalian morphogens, bone morphogenetic proteins-2
      and -4 (BMP-2 and -4). Very little is known regarding the molecular events that
      govern such human lineage decisions. In this study, the role of the ID (inhibitor
      of differentiation and DNA-binding) family of genes that act as inhibitors of the
      function of helix-loop-helix (HLH) transcriptional activators involved in lineage
      commitment was investigated using two pluripotential GCT cell lines as a model
      system. In the differetiation programs studied, Id1 was noted to decline, an
      event often associated with the decrease in proliferative rate occurring during
      differentiation. However, differences in the expression of ID2 and ID3 family
      members were detected between the programs. Notably, an increase in Id3 during RA
      induced differentiation of NT2/D1 cells was observed, while Id2 levels increased
      during BMP-2 and -4 treatment of NT2/D1 cells and during the induction of an
      endodermal-like differentiation program in the cell line, 27X-1. The
      pluripotential male GCT cell lines comprise a unique system in which the roles of
      specific genes such as the ID family of genes in human cell differentiation and
      lineage decision can be studied.

PMID- 11320654
TI  - Immuno-characterisation of neuroendocrine cells of the rat thymus gland in vitro
      and in vivo.
AB  - Primary cell cultures and organ fragments of rat thymus were characterised by use
      of a panel of antibodies raised against the neural adhesion molecule L1, tyrosine
      hydroxylase, protein gene product 9.5, nerve growth factor, calcitonin gene
      related peptide, glial fibrillary acidic protein, vimentin, pan-cytokeratin, a
      ganglioside of neural crest and neuroendocrine cells (A2B5), and thymulin (4
      beta). Immunoreactivity for neural markers only was identified in a single
      morphology (nerve-like) of cell in culture and throughout the adult thymus as
      fine, tortuous staining. Immunoreactivity for endocrine markers only was
      identified in polygonal epithelial-like cells in culture, throughout viable
      tissue in fragment culture and in the subcapsular cortex of the adult thymus.
      Immunoreactivity for both endocrine and neural markers was identified in three
      distinct morphologies in cell culture: elongate, spherical, and stellate. Similar
      results were observed in the mitotic periphery of the cultured fragments and in
      the medulla and cortico-medullary junction of the adult thymus. Cells with
      immunoreactivity to A2B5 were present in primary and fragment cultures and
      occurred throughout the adult thymus. The apparent diversity of cell
      immunoreactivity in primary and fragment thymic cultures suggests that numerous
      neural and endocrine factors may be required for the development and/or
      regeneration of the thymic microenvironment.

PMID- 11320655
TI  - A DiI-tracing study of the neural connections of the pineal organ in two
      elasmobranchs (Scyliorhinus canicula and Raja montagui) suggests a pineal
      projection to the midbrain GnRH-immunoreactive nucleus.
AB  - The pineal organ of elasmobranchs is an elongated photoreceptive organ. In order
      to investigate the afferent and efferent connections of the pineal organ of two
      elasmobranchs, the skate (Raja montagui) and the dogfish (Scyliorhinus canicula),
      a fluorescent carbocyanine (DiI) was applied to the pineal organ of
      paraformaldehyde-fixed brains. This application strongly labeled the pineal
      tract, which formed extensive bilateral projections. In both species, the
      pinealofugal fibers coursed to the dorsomedial thalamus, the medial pretectal
      area, the posterior tubercle, and the medial mesencephalic tegmentum and branched
      profusely in these areas. Application of DiI to the pineal organ also labeled
      occasional perikarya in the dorsomedial thalamus, posterior commissural region,
      posterior tubercle, and mesencephalic tegmentum. A comparison of these results
      with those of immunocytochemical analyses of the dogfish brain with an anti
      salmon gonadotropin-releasing hormone (sGnRH) antiserum revealed a close
      topographical relation between the pineal projections and the midbrain sGnRH
      immunoreactive (ir) nucleus, the only structure in the dogfish brain that
      contained sGnRHir neurons. This and the widespread distribution of sGnRHir fibers
      in the brain suggest that the midbrain sGnRHir nucleus is a part of the secondary
      pineal pathways and may be involved in light-mediated pineal regulation of brain
      function. Although GnRH distribution has not been studied in the skate, a
      midbrain GnRHir nucleus has been identified in three other elasmobranchs,
      including a skate relative. The probable existence of direct pineal projections
      to the GnRHir midbrain nucleus in elasmobranchs and other anamniotes is
      discussed.

PMID- 11320656
TI  - Double immunocytochemistry of vasoactive intestinal peptide and cGnRH-I in male
      quail: photoperiodic effects.
AB  - Reproduction in Japanese quail is primarily regulated by photoperiod. Vasoactive
      intestinal peptide (VIP) has been suggested as a transducer of environmental
      information, especially photoperiodic cues, to the hypothalamo-pituitary-gonadal
      axis. To investigate the possible interaction of VIP and the reproductive
      (gonadotropin-releasing hormone, GnRH) system, double-immunocytochemical staining
      for VIP and cGnRH-I was conducted in sexually mature male quail held under a long
      day photoperiod (16L:8D; LD) and in sexually quiescent males held under a short
      day photoperiod (8L:16D; SD). VIP-immunoreactive (ir) cells were found primarily
      in three locations: lateral septal organ (LSO) in nucleus accumbens (Ac), ventral
      hypothalamus, and infundibular area. VIP-ir cells in LSO displayed
      characteristics typical of cerebrospinal fluid (CSF)-contacting cells, and co
      existed with cGnRH-I-ir cells and beaded fibers. In contrast, VIP-ir cells in the
      infundibular area did not co-exist with cGnRH-I-ir structures. The number of
      visible VIP-ir cells in the infundibular area of SD males was significantly lower
      than that of LD males, while the number of visible VIP-ir cells in Ac/LSO was not
      altered by photoperiod. A cluster of cGnRH-I-ir cells in the caudalmost septal
      area was heavily innervated by VIP-ir fibers, which appeared to contact cGnRH-I
      ir cells directly at this location. Both VIP- and cGnRH-I-ir fibers heavily
      innervated the external layer of the median eminence (ME). These data suggest
      that Ac/LSO, the caudalmost septal area, and ME are possible sites of interaction
      between the VIP and the GnRH systems.

PMID- 11320657
TI  - Functionally impaired, hypertrophic ECL cells accumulate vacuoles and lipofuscin
      bodies. An ultrastructural study of ECL cells isolated from hypergastrinemic
      rats.
AB  - ECL cells in the oxyntic mucosa of stomach control gastric acid secretion by
      mobilizing histamine in response to gastrin. They respond to gastrin also with
      hypertrophy and hyperplasia. ECL cells exhibit functional impairment upon long
      term gastrin stimulation. The impairment is manifested in a gradual decline of
      the activity of the histamine-forming enzyme per individual ECL cell and in a
      failure of gastrin to mobilize histamine. The mechanism behind this impairment is
      unknown. In the present study, rats were treated with the proton pump inhibitor
      pantoprazole for 45 days to induce sustained hypergastrinemia. The ECL cells were
      isolated from normogastrinemic and hypergastrinemic rats and size-separated from
      other mucosal cells by the elutriation technique. The total ECL cell number was
      twofold higher in hypergastrinemic rats than in normogastrinemic rats, and most
      of the cells appeared in elutriation fractions where large cells predominate. The
      ECL cells of the different fractions were analyzed by quantitative electron
      microscopy. Normal-sized ECL cells from hypergastrinemic rats displayed a reduced
      number of secretory vesicles (probably because of degranulation) compared with
      normal-sized ECL cells from normogastrinemic rats. Hypertrophic ECL cells from
      hypergastrinemic rats had an unchanged number of secretory vesicles, supporting
      the view that such cells fail to respond to gastrin with degranulation. Although
      both normal-sized and hypertrophic ECL cells from hypergastrinemic rats contained
      vacuoles, those in the hypertrophic ECL cells were larger and more numerous. In
      addition, hypertrophic ECL cells were found to contain numerous, prominent
      lipofuscin bodies which are the presumed end product of crinophagia. Conceivably
      therefore, large vacuoles and lipofuscin bodies cause functional impairment of
      the hypertrophic ECL cells.

PMID- 11320658
TI  - Microglia play a role in mediating the effects of cytokines on the structure and
      function of the rat pineal gland.
AB  - The role of the pineal gland in regulating immune function has been extensively
      investigated. However, there is little information about possible feedback
      mechanisms of immunological factors on pineal gland neuroendocrine functions.
      Therefore, experiments were designed to test the effects of cytokines (interferon
      gamma, IFN-gamma, interleukin-1 beta, IL-1 beta; tumor necrosis factor-alpha, TNF
      alpha; transforming growth factor-beta 1, TGF-beta 1) on pinealocytes and the
      role of pineal microglia in mediating these cytokine effects in the pineal gland
      of the rat. Our studies showed that IFN-gamma enhanced 5-hydroxytryptamine (5-HT)
      content (measured by high-performance liquid chromatography, HPLC) and increased
      pinealocyte process length in pineal cultures. IL-1 beta treatment decreased 5-HT
      content in both cell and organ culture, but exhibited no effect on pinealocyte
      process length. 5-HT content and process length were decreased by TNF-alpha
      treatment. IFN-gamma and IL-1 beta exhibited no significant effect in the absence
      of microglia in cell cultures. In contrast, TNF-alpha caused a further decline in
      5-HT content even in the absence of microglia in the cultures. The effects of TNF
      alpha were probably due to toxic effects, since an increased number of pyknotic
      nuclei were observed in treated cultured explants. TGF-beta 1 treatment caused
      aggregation of pinealocytes in cultures and suppressed process length and 5-HT
      content. In conclusion, cytokine effects on pinealocytes may be mediated by
      microglia (IFN-gamma and IL-1 beta) or act directly on pinealocytes (TNF-alpha).
      The presence of IL-1 beta and TGF-beta 1 protein in the pineal gland and the
      suppressive effect of TGF-beta 1 on pinealocytes in cultures further suggest that
      endogenous cytokines play regulatory roles in response to peripheral homeostatic
      changes.

PMID- 11320659
TI  - Expression of SNMP-1 in olfactory neurons and sensilla of male and female
      antennae of the silkmoth Antheraea polyphemus.
AB  - SNMP-1 (sensory neuron membrane protein 1) is an olfactory-specific membrane
      bound protein which is homologous with the CD36 receptor family. Previous light
      level immunocytochemical studies suggested that SNMP-1 was localized in the
      dendrites and distal cell body of sex-pheromone-specific olfactory receptor
      neurons (ORN); these studies further suggested SNMP-1 was expressed in only one
      of two to three neurons in male-specific pheromone-sensitive trichoid sensilla.
      To better understand the expression and localization of SNMP-1, an
      immunocytochemical study was performed using electron microscopy to visualize the
      distribution of SNMP-1 among the neurons of several classes of olfactory sensilla
      of both male and female antennae of the silkmoth Antheraea polyphemus. SNMP-1
      antigenicity was primarily restricted to the receptive dendritic membranes of
      ORNs of all sensilla types examined and was observed in cytosolic granules, but
      not plasma membranes, of the cell soma. Mean labeling densities ranged from 1 to
      16 gold particles per micrometer of dendrite circumference; dendrites of trichoid
      and intermediate sensilla showed significantly higher labeling densities than
      those of basiconic sensilla. Larger dendrites of trichoid sensilla showed
      significantly higher mean labeling densities (13-16/micron) than smaller diameter
      dendrites (3-7/micron). Immunofluorescence studies using baculovirus expressed
      SNMP-1 and multiphoton photon laser scanning microscopy (MPLSM) indicated that
      rSNMP-1, which was post-translationally processed to the in vivo molecular
      weight, was inserted into the plasma membrane in a topography presenting
      extracellular epitopes. These studies suggest SNMP-1 is a common feature of the
      ORNs, is asymmetrically expressed among functionally distinct neurons, and
      possesses a topography which permits interaction with components of the
      extracellular sensillum lymph.

PMID- 11320660
TI  - Increased intracellular content of enteroglucagon in proximal colon is related to
      intestinal adaptation to germ-free status.
AB  - Changes in the frequency of endocrine cells are evidence of intestinal adaptation
      to germ-free (GF) status. Not only the distribution of these cells along the
      intestine, but also the differences in intracellular content of these regulatory
      peptides may be explored to explain functional and structural aspects of GF
      intestinal adaptation. Focusing on the endocrine L-cells, we analyzed the
      intracellular content of enteroglucagon (EG) and peptide YY (PYY) throughout the
      intestine of the 14 GF and 14 conventional (CV) mice by using
      immunohistochemistry and the supra-optimal dilution technique. The percentage of
      EG-immunoreactive cells, but not of PYY-immunoreactive cells stained at supra
      optimal dilution was significantly higher in the proximal colon of GF mice than
      in the CV counterparts (P < 0.05). Since the content of co-stored PYY did not
      differ between GF and CV mice, the higher content of EG was compatible with a
      selective cellular response. Moreover, in the cecum of GF mice, the density of EG
      immunoreactive cells was significantly higher than that of PYY-immunoreactive
      cells (P < 0.05). These results are consistent with preferential production of EG
      by L-cells at the expense of PYY in the proximal colon and in the enlarged cecum
      of GF mice. In addition, they may reflect the dynamics of the GF intestinal
      epithelium and/or be correlated with the higher serum levels of these peptides.
      The role of endocrine cells needs to be better studied in human and other
      experimental adaptative conditions in order to elucidate the regulatory
      mechanisms of intestinal functions.

PMID- 11320661
TI  - Novel mechanism of cellular DNA topoisomerase II inhibition by the
      pyranonaphthoquinone derivatives alpha-lapachone and beta-lapachone.
AB  - PURPOSE: The mechanisms of intracellular topoisomerase II inhibition by the
      pyranonaphthoquinone derivatives alpha-lapachone and beta-lapachone were studied.
      METHODS: Cell-based mechanistic studies were designed based on the in vitro
      mechanisms [17] and primarily involved the use of cultured KB (nasopharyngeal
      tumor cells) cells and the etoposide-resistant sub-line KB-7d. RESULTS: The KB-7d
      cells exhibited collateral sensitivity to alpha-lapachone; this supports the
      possibility of catalytic inhibition of topoisomerase II in the cells.
      Interestingly, both compounds induced an increase (two- to threefold) in
      reversible double-stranded DNA breaks in cell lines with a reduced expression of
      topoisomerase II. However, these drug-induced DNA breaks became irreversible at
      treatment times greater than 1 h. Studies showed that DNA breaks in KB-7d cells
      were not caused by endonucleases. Use of antioxidants abolished the appearance of
      cellular DNA breaks; this suggests involvement of the oxidation-reduction cycle
      of pyranonaphthoquinones in topoisomerase II inhibition; however, irreversible
      DNA breaks were not a result of drug-induced oxidative stress. CONCLUSIONS: On
      the basis of the findings, it is proposed that the compounds, on longer
      incubation with cells, induce abortive dissociation of topoisomerase II from the
      DNA, leading to an irreversible accumulation of high molecular weight DNA
      fragments. In addition to establishing topoisomerase II as an intracellular
      target of alpha-lapachone, the results suggest that both compounds can be
      classified as neither typical poisons nor as typical catalytic inhibitors of the
      enzyme. In summary, both compounds are members of a new inhibitor class, and
      alpha-lapachone, in particular, can be considered a potential lead for the
      development of drugs to treat multidrug-resistant cell lines with lower
      expression of topoisomerase II.

PMID- 11320662
TI  - Plasma pharmacokinetics and cerebrospinal fluid penetration of thioguanine in
      children with acute lymphoblastic leukemia: a collaborative Pediatric Oncology
      Branch, NCI, and Children's Cancer Group study.
AB  - PURPOSE: In preclinical studies, thioguanine (TG) has been shown to be more
      potent than the standard acute lymphoblastic leukemia (ALL) maintenance agent,
      mercaptopurine (MP), suggesting that TG may be more efficacious than MP in the
      treatment of childhood ALL. As part of a pilot trial in which TG was used in
      place of MP, we studied the plasma pharmacokinetics of oral TG and measured
      steady-state plasma and CSF TG concentrations during a continuous intravenous
      infusion (CIVI) in children with newly diagnosed standard-risk ALL. METHODS: Nine
      plasma samples were collected after each patient's first 60 mg/m2 oral TG dose
      during maintenance. CIVI TG (20 mg/m2/h over 24 h) was administered during the
      consolidation phase of therapy, and simultaneous plasma and CSF samples were
      collected near the end of the infusion. TG was measured by reverse-phase HPLC
      with ultraviolet detection. Erythrocyte TG nucleotide (TGN) concentrations were
      measured 7 days after a course of CIVI TG and prior to the start of each
      maintenance cycle. RESULTS: After oral TG (n = 35), the mean (+/- SD) peak plasma
      concentration was 0.46 +/- 0.68 microM and the AUC ranged from 0.18 to 9.5
      microM.h (mean 1.5 microM.h). Mean steady-state plasma and CSF TG concentrations
      during CIVI (n = 33) were 2.7 and 0.5 microM, respectively. The mean (+/- SD) TG
      clearance was 935 +/- 463 ml/min per m2. Plasma TG concentrations did not
      correlate with erythrocyte TGN concentrations after oral or CIVI TG. The 8-OH-TG
      metabolite was detected in plasma and CSF. CONCLUSIONS: TG concentrations that
      are cytotoxic to human leukemia cell lines can be achieved in plasma after a 60
      mg/m2 oral dose of TG and in plasma and CSF during CIVI of TG.

PMID- 11320663
TI  - A phase II study of dose-intense ifosfamide plus epirubicin with hematopoietic
      growth factors for the treatment of patients with advanced soft tissue sarcomas;
      a novel sequential schedule.
AB  - PURPOSE: The efficacy and feasibility of a novel sequential schedule of high-dose
      ifosfamide (HD-IFO) and full-dose epirubicin (EPI) with granulocyte colony
      stimulating factor (G-CSF) was evaluated in adult patients with soft tissue
      sarcomas (STS). METHODS: Since November 1995, 22 chemotherapy-naive patients have
      been treated. HD-IFO was given as a continuous infusion at a total dose of 14-18
      g/m2 per cycle, with mesna, over 6 to 8 days, q 3 weeks, twice. EPI was
      administered subsequently as an i.v. bolus at a total dose of 120-160 mg/m2, on
      days 1-2, q 2 weeks, twice. G-CSF was planned for each course of treatment as a
      daily subcutaneous injection for 7 days, starting 24 h after the end of the
      treatment. After the first four cycles, patients were evaluated for surgery and
      patients with locally inoperable or metastatic disease received further
      chemotherapy up to a maximum of eight cycles. RESULTS: The response of 19
      patients could be assessed. One complete response (CR) and six partial responses
      (PRs) were achieved for an overall response rate of 37% (95% confidence interval,
      15-59%). Noteworthy is that two of the six leiomyosarcoma patients responded to
      the HD-IFO treatment. The median survival period was 15 months. Most common
      toxicities included myelosuppression, nausea and vomiting, and stomatitis. Six
      patients were hospitalized for complicated nadir fever. No severe renal and CNS
      toxicities were seen. Transient gross hematuria occurred in six patients and
      affected treatment in only one case. There were no treatment-related deaths.
      CONCLUSIONS: By the protraction of continuous infusion of HD-IFO over 6 to 8
      days, ifosfamide-induced acute renal toxicity is avoided, while G-CSF support
      allows the delivery of the planned dose intensity in most of the patients.
      Although manageable in an oncology setting, the hematologic toxicity of such a
      regimen remains substantial. Moreover, in terms of efficacy and median survival,
      this regimen showed no benefits over a conventional-dose anthracycline-ifosfamide
      schema. Further evaluations of this novel ifosfamide-epirubicin schedule are not
      warranted, even if the HD-IFO regimen could be taken forward specifically for
      leiomyosarcomas in a phase II trial.

PMID- 11320664
TI  - Development, characterization and therapy of a disseminated model of childhood
      neuroblastoma in SCID mice.
AB  - PURPOSE: To develop a highly reproducible model of disseminated childhood
      neuroblastoma in mice to allow secondary evaluation of therapeutics against
      microscopic disseminated disease. METHODS: CB17/Icr SCID were injected i.v. with
      10(3) to 5 x 10(6) human NB-1691 neuroblastoma cells. NB-1691 cells were detected
      by PCR for synaptophysin and tyrosine hydroxylase in peripheral blood, and bone
      marrow. Therapeutic studies evaluated topotecan and vincristine as single agents
      or in combination. Topotecan was administered i.v. daily for 5 days on two
      consecutive weeks. Courses were repeated every 21 days for three cycles.
      Vincristine (1 mg/kg) was administered i.v. every 7 days for nine consecutive
      weeks. Treatment started 11-21 days after tumor cell inoculation. RESULTS:
      Following injection of > or = 1 x 10(5) cells 100% of mice developed disease.
      Mice inoculated with 10(7) cells survived a median of 42 days. Survival time was
      a linear function of the cell inoculum. At autopsy, gross tumor was routinely
      detected in many organs in particular liver, ovaries, kidneys and adrenals. NB
      1691 cells were detected by PCR in peripheral blood, and bone marrow.
      Immunohistochemical staining showed that lesions were strongly positive for
      synaptophysin, chromogranin A and negative for leukocyte common antigen.
      Topotecan (0.6 mg/kg) alone extended median survival from 44 days (controls) to
      95 days. When treatment was started 21 days after inoculation of NB-1691 cells,
      topotecan extended median survival from 39 days (controls) to 91 and 99 days at
      dose levels of 0.3 and 0.6 mg/kg, respectively. Vincristine (1 mg/kg) extended
      survival by a median of 9.5 days. In combination with vincristine (1 mg/kg),
      median survival was increased to 141 days (topotecan 0.6 mg/kg) and 159 days
      (topotecan 1.0 mg/kg). CONCLUSION: This model of disseminated neuroblastoma is
      highly reproducible. As this model may more closely simulate childhood disease it
      may be a valuable adjunct in developing new approaches to advanced stage, poor
      prognosis neuroblastoma.

PMID- 11320665
TI  - Cyclophosphamide metabolism in children following a 1-h and a 24-h infusion.
AB  - PURPOSE: The pharmacokinetics and metabolism of cyclophosphamide (CPA) when given
      as a 1-h and a 24-h infusion to children were compared. METHODS: Thirteen
      children with a variety of different malignancies received an identical dose of
      cyclophosphamide as a 1- and 24-h infusion. In each case the concentration of CPA
      and its principal metabolites were measured by a thin-layer-chromatography
      photographic-densitometry technique. RESULTS: Cyclophosphamide clearance was
      greater during the 24-h infusion, following time-dependent increases in the
      metabolism of the drug (autoinduction) (median 5.1 vs 3.1 l/h/m2: P = 0.037).
      Autoinduction was seen in five children (38%), producing a median end of infusion
      concentration of 49% (range 28-89%) of the maximum and was not accompanied by an
      increase in the production of the principal inactive metabolites
      carboxyphosphamide and dechloroethylcyclophosphamide. CONCLUSIONS: These results
      suggest potential benefits of prolonging the infusion of CPA in clinical
      practice.

PMID- 11320666
TI  - Cytocidal effect and DNA damage of nedaplatin: a mathematical model and analysis
      of experimental data.
AB  - PURPOSE: Cell cycle non-specific anticancer agents such as cis
      diamminedichloroplatinum(II) are believed to depend linearly on the value of the
      area under the drug concentration time curve, which is supported by a
      mathematical model. However, the quantitative non-linear phenomena of both the
      cytocidal effect and DNA crosslink formation by cisdiammine(glycolato)platinum
      (nedaplatin) have been shown in vitro. Therefore, we developed a new mathematical
      model to explain these phenomena. METHODS: We assumed that nedaplatin enters
      intracellular fluid from medium through simple diffusion to form DNA crosslinks
      that kill cells. We developed a mathematical model to represent this assumption
      using differential equations that we then solved using an original computer
      program. The calculated results were compared with the experimental data.
      RESULTS: The drug's simple diffusion rate constant, the DNA crosslink formation
      rate constant, and the crosslink-dependent cell death rate constant in the model
      were 1.8 x 10(-14) (l h-1), 1.6 x 10(8) (l mol-1/2 h-1), 5.45 x 10(1) (mol-1),
      respectively. The model fits the experimental results statistically. The model
      also demonstrated theoretical proof that continuous exposure at a low dose was
      superior to the short exposure at a high dose seen in published experimental
      data. CONCLUSIONS: We developed a mathematical model to describe the non-linear
      pharmacodynamic effect of nedaplatin in vitro. This model may provide a novel
      drug infusion procedure for cancer patients.

PMID- 11320667
TI  - Comparative study of a novel nucleoside analogue (Troxatyl, troxacitabine, BCH
      4556) and AraC against leukemic human tumor xenografts expressing high or low
      cytidine deaminase activity.
AB  - PURPOSE: Troxacitabine (beta-L-dioxolane cytidine, BCH-4556; Troxatyl, BioChem
      Pharma Inc.) is a novel nucleoside analogue, which in experiments demonstrated
      potent antitumor activity against both leukemias and solid tumors. Since
      troxacitabine is a cytidine nucleoside analogue like AraC (1-beta-D
      arabinofuranosylcytosine), which is currently used in the treatment of acute
      myelogenous leukemia, we compared the in vivo antileukemic activity of
      troxacitabine with that of AraC in human leukemia xenograft models. METHODS: The
      antiproliferative activity of troxacitabine and AraC was analyzed on hemapoietic
      cell lines by use of a thymidine incorporation assay. For in vivo studies, we
      compared troxacitabine with AraC by using equitotoxic schedules of the two
      nucleosides optimized for therapeutic activity. The antileukemic activity of both
      drugs was evaluated by measurement of their effect on the percent increased
      lifespan. RESULTS: AraC had good in vitro antiproliferative activity (IC50 = 14
      nM) but was ineffective in vivo against the HL60 promyelocyte leukemia cell line
      (treated vs control, T/C = 105%). Troxacitabine, which in contrast to AraC is not
      a substrate for cytidine deaminase, showed potent in vitro and in vivo activity
      in the same model (IC50 = 53 nM and T/C = 272% to 422%). The poor in vivo
      activity of AraC against HL60 leukemia cells could be due to the high cytidine
      deaminase (CDA; EC 3.5.4.5) activity in this cell line. This hypothesis was
      tested with CCRF-CEM T-lymphoblastoid leukemia cells which have undetectable
      levels of CDA activity. Short-term exposure of these leukemia cell lines to both
      drugs indicated that AraC was indeed significantly more effective in the CCRF-CEM
      cell line than in HL60. In contrast, the antiproliferative activity of
      troxacitabine was similar for both cell lines. These observations were extended
      to in vivo studies. Mice bearing CCRF-CEM tumor xenografts were treated with AraC
      and troxacitabine. In this model, T/C values were comparable for both drugs and
      ranged from 138% to 157%. CONCLUSIONS: Our findings indicate that troxacitabine
      is likely to be effective not only against solid tumors with high CDA activity
      but also in leukemias which have developed resistance to AraC due to increased
      CDA levels; this suggests that troxacitabine is a promising agent for the
      treatment of cancer. Indeed, significant antileukemic activity has been observed
      with troxacitabine in a phase I clinical trial in patients with primary
      refractory or relapsed acute myeloid leukemias (AML).

PMID- 11320668
TI  - Bisimidazoacridones induce a potent cytostatic effect in colon tumor cells that
      sensitizes them to killing by UCN-01.
AB  - PURPOSE: To determine the ability of WMC26, a prototypic bisimidazoacridone
      (BIA), to induce apoptosis in sensitive colon adenocarcinoma cells and to advance
      the hypothesis that cancer cells that are growth-arrested by WMC26 are
      predisposed to undergo apoptotic death by abrogators of cell cycle checkpoints.
      METHODS: The antiproliferative activity of WMC26 was examined in detail by a 4
      day MTT assay, cell counting, BrdU incorporation and a two-color LIVE/DEAD assay.
      To detect apoptosis a number of established techniques were used, including gel
      electrophoresis, flow cytometry, and confocal laser microscopy of treated cells.
      The activity of senescence-associated beta-galactosidase in treated cells was
      also analyzed. RESULTS: WMC26, at physiological concentrations, induced complete
      and longlasting growth arrest of HCT116 cells in culture but did not trigger cell
      death. The growth-arrested cells (blocked at G1 and G2/M cell cycle checkpoints)
      did not synthesize DNA but were metabolically active and had intact plasma
      membranes. Although they resembled the senescence-like phenotype reported to be
      induced by treatment with some antitumor agents, the cells did not express
      senescence-associated beta-galactosidase, an indicator of the senescence-like
      state. Treatment of WMC26 growth-arrested cells with 1 microM UCN-01, an
      abrogator of the G2/M checkpoint, caused a very rapid (1 h) change in morphology
      and cell death within 72 h. CONCLUSIONS: BIAs do not induce apoptosis in
      sensitive colon tumor cells. They are highly cytostatic but only marginally toxic
      to the cells even at concentrations 100-fold higher than those sufficient for
      complete growth arrest. In this respect WMC26 differs from some other DNA
      interacting antitumor agents that produce cell growth arrest at low
      concentrations but are toxic at higher doses. The complete growth arrest induced
      by WMC26 in colon cancer cells sensitized them to apoptotic death induced by UCN
      01. This finding suggests that a combination of WMC26 and cyclin-dependent kinase
      inhibitors may be an attractive treatment method for colon cancer that utilizes
      the highly tumor-selective activity of WMC26.

PMID- 11320669
TI  - Effects of PR-350, a newly developed radiosensitizer, on dihydropyrimidine
      dehydrogenase activity and 5-fluorouracil pharmacokinetics.
AB  - This study was designed to investigate the effects of PR-350, a newly developed
      radiosensitizer, on dihydropyrimidine dehydrogenase (DPD) activity and 5
      fluorouracil (5-FU) pharmacokinetics in 8-week-old male Sprague-Dawley rats. In
      an in vitro study with hepatic cytosol, DPD activity was dose-dependently reduced
      by PR-350 at 0.5, 1.0, and 2.0 mmol/l to 75.5%, 64.9%, and 61.5%, respectively,
      of the control values. In an ex vivo study, DPD activities in hepatic cytosols
      obtained from animals which had received PR-350 over 4 days (200 mg/kg per day)
      were not significantly different from those in animals which had not. In an in
      vivo study, none of the pharmacokinetic parameters obtained from the plasma
      concentration-time profile of 5-FU were significantly altered by single i.v.
      injections of PR-350 (50, 100, or 200 mg/kg). However, (E)-5-(2)
      (bromovinyl)uracil (BVU), a DPD inhibitor, significantly increased the half-life
      and area under the curve of 5-FU to 238.1% and 323.2%, respectively, of the
      control values. Administration of PR-350 over 4 days (200 mg/kg per day) did not
      affect either of these parameters. The administration of PR-350 significantly
      reduced the clearance (73.5% of control) and volume of distribution (71.0% of
      control) of 5-FU, but the alterations were much less than those caused by BVU.
      These results suggest that the effect of PR-350 on 5-FU pharmacokinetics is much
      less than that of BVU and that the enhancement of 5-FU toxicity by PR-350 is less
      than we initially anticipated.

PMID- 11320670
TI  - Primary breast tumor levels of suspected molecular determinants of cellular
      sensitivity to cyclophosphamide, ifosfamide, and certain other anticancer agents
      as predictors of paired metastatic tumor levels of these determinants. Rational
      individualization of cancer chemotherapeutic regimens.
AB  - PURPOSE: Cyclophosphamide is one of the most frequently used agents in the
      neoadjuvant, adjuvant, and high-dose chemotherapeutic treatment of breast
      cancers. Preclinical models indicate that cellular sensitivity to
      cyclophosphamide and other oxazaphosphorines, e.g., ifosfamide, is inversely
      related to the cellular content of two aldehyde dehydrogenases, viz ALDH1A1 and
      ALDH3A1, and glutathione. Breast tumor levels of these "determinants of cellular
      sensitivity to the oxazaphosphorines" are known to vary widely, and the decision
      as to whether or not to use an oxazaphosphorine as part of the therapeutic
      strategy to treat breast cancer in any given patient is likely to depend, in
      large part, on the levels of these determinants in that cancer. ALDH1A1, ALDH3A1,
      and glutathione levels can be easily quantified in primary breast tumors and in
      detectable metastatic breast tumors present in axillary lymph nodes because the
      amounts of tissue required for the desired analysis can be readily obtained,
      whereas these levels cannot be quantified in residual metastatic breast cancer
      cell populations, i.e., those that escape detection and/or that are inaccessible
      to surgical harvest. The inability to directly quantify residual metastatic
      breast cancer cell ALDH1A1, ALDH3A1, and glutathione levels would not preclude a
      rational decision with regard to the inclusion/exclusion of an oxazaphosphorine
      as part of the chemotherapeutic strategy intended to eradicate residual
      metastatic breast cancer cells if primary breast tumor levels of these
      determinants reliably predicted those in metastatic breast cancer cells. METHODS:
      ELISAs and spectrophotometric assays were used to quantify enzyme and glutathione
      levels in paired human primary and locally advanced metastatic breast tumor
      samples. RESULTS: Primary breast tumor ALDH1A1 and ALDH3A1 levels were highly
      predictive of their respective levels in paired metastatic breast tumors present
      in axillary lymph nodes (r2 = 0.80 and 0.85, respectively). On the other hand,
      those of glutathione were relatively poorly predictive of its levels in paired
      metastatic offshoots (r2 = 0.35). Primary breast tumor levels of some additional
      enzymes known to catalyze the detoxification/toxification of various anticancer
      agents, though not of cyclophosphamide, were poorly predictive (DT-diaphorase and
      glutathione S-transferases alpha, mu, and pi) or not predictive (cytochrome P450
      1A1) of their respective levels in paired metastatic offshoots. CONCLUSION: Since
      ALDH1A1, ALDH3A1 and, to a lesser extent, glutathione levels in primary breast
      tumors reliably predicted those in detectable and easily accessible metastatic
      breast cancer cell populations, viz those in axillary lymph nodes, they are also
      likely to be predictive of these levels in undetectable and/or relatively
      inaccessible metastatic breast cancer cell populations. Thus, quantification of
      primary breast tumor ALDH1A1, ALDH3A1 and, to a lesser extent, glutathione levels
      prior to the initiation of not only neoadjuvant but also adjuvant and high-dose
      breast cancer chemotherapy is likely to be of value in the rational design of
      individualized chemotherapeutic regimens intended to eradicate breast cancer
      cells with a minimum of untoward effects.

PMID- 11320671
TI  - Pharmacokinetics of deguelin, a cancer chemopreventive agent in rats.
AB  - PURPOSE: To study the pharmacokinetics of deguelin, a naturally occurring
      potential cancer chemopreventive agent, in rats. METHODS: [3H]Deguelin was
      administered intravenously (i.v.) under anesthesia, and blood samples were
      collected over 24 h. [3H]Deguelin and metabolites were extracted from plasma with
      ethyl acetate, and quantified by HPLC. Data were analyzed with the WinNolin
      pharmacokinetic software package to determine pharmacokinetic parameters. A three
      compartment first-order elimination model was used to fit the plasma
      concentration-time curve. In addition, deguelin concentrations in tissues after
      i.v. and intragastric (i.g.) administration were determined by HPLC, and
      excretion (feces and urine) was evaluated over a 5-day period after i.g.
      administration. RESULTS: Deguelin exhibited a mean residence time (MRT) of 6.98 h
      and terminal half-life (t1/2(gamma)) of 9.26 h. The area under the curve (AUC)
      and total clearance (Cl) were 57.3 ng.h/ml and 4.37 l/h per kg, respectively,
      with an apparent volume of distribution (V) and volume of distribution at steady
      state (Vss) of 3.421 l/kg and 30.46 l/kg, respectively. Following i.v.
      administration, the relative levels of tissue distribution were as follows: heart
      > fat > mammary gland > colon > liver > kidney > brain > lung. Following i.g.
      administration, the relative levels of tissue distribution were as follows:
      perirenal fat > heart > mammary gland > colon > kidney > liver > lung > brain >
      skin. Within 5 days of i.g. administration, about 58.1% of the [3H]deguelin was
      eliminated via the feces and 14.4% via the urine. Approximately 1.7% of unchanged
      deguelin was found in the feces, and 0.4% in the urine. CONCLUSIONS: An initial
      pharmacokinetic investigation of deguelin showed that this rotenoid has a
      relatively long MRT and half-life in plasma in the rat. The compound distributed
      in the tissues and excreted as metabolites, mainly via the feces.

PMID- 11320673
TI  - Typhlitis (neutropenic enterocolitis) after a single dose of vinorelbine.
AB  - We report a case of a 50-year-old man with pretreated adenocarcinoma of the lung,
      who developed fatal neutropenic enterocolitis (typhlitis) after a standard dose
      of the cytotoxic drug vinorelbine. Blood cultures were negative for all
      microorganisms tested for. Stool cultures were negative for enteric rods but
      direct examination of fresh stool revealed the presence of Giardia lamblia.
      Abdominal pain and diarrhoea developed very rapidly while the patient was only
      moderately neutropenic. Metronidazole was prescribed without clinical benefit:
      the abdominal pain remained stable. The duration of neutropenia was very short (4
      days). The abdominal catastrophe ending in shock occurred after complete recovery
      of the neutrophil count. Neutropenic colitis has been reported with increasing
      frequency in solid tumours after the introduction of taxanes. This complication
      has been observed mainly in phase I studies, near the maximally tolerated doses
      (MTD). The combined use of vinorelbine has recently been reported to exacerbate
      the toxic effects of taxane on the colon. The case presented here demonstrates
      that typhlitis can occur even with vinorelbine alone, used at a standard
      recommended dose (30 mg/m2).

PMID- 11320672
TI  - Impact of carrier solutions on pharmacokinetics of intraperitoneal chemotherapy.
AB  - PURPOSE: In the treatment of gastrointestinal malignancies with dissemination to
      peritoneal surfaces the principal advantage of intraperitoneal chemotherapy over
      intravenous chemotherapy is the high drug concentration achieved locally with low
      systemic toxicity. This advantage can be optimized by maintaining a large area of
      contact between the chemotherapy solution and the surfaces within the abdomen and
      pelvis over a prolonged time period. Using a rat model we compared the
      pharmacokinetics of two drugs infused intraperitoneally, 5-fluorouracil and
      gemcitabine, in five different carrier solutions. METHODS: A total of 120 Sprague
      Dawley rats were randomized into groups according to the carrier solution and the
      drug administered. Rats were given a single dose of intraperitoneal 5
      fluorouracil (20 mg/kg) or gemcitabine (12.5 mg/kg) in 0.1 ml/g body weight of
      each carrier solution. The carrier solutions used varied in their tonicity (0.3%,
      0.9% or 3% sodium chloride), or were isotonic and varied in molecular weight
      (0.9% sodium chloride, 4% icodextrin and 6% hetastarch). With the hypotonic,
      isotonic and hypertonic sodium chloride solutions, only 5-fluorouracil was used.
      Each group was further randomized according to the intraperitoneal dwell period
      (1, 3 or 6 h). At the end of the procedure the rats were killed, the peritoneal
      fluid was withdrawn completely and the blood was sampled using a standardized
      protocol. The volume of the peritoneal fluid was recorded, and the drug
      concentrations in the peritoneal fluid and plasma were determined by high
      performance liquid chromatography. RESULTS: Measurements of peritoneal fluid
      volume showed a more rapid clearance of hypotonic and isotonic sodium chloride
      solutions from the peritoneal cavity as compared to hypertonic sodium chloride
      and high molecular weight solutions. When comparing the remaining intraperitoneal
      volumes at 6 h, the differences were statistically significant for both 5
      fluorouracil and gemcitabine when hetastarch (P < 0.0001 and P = 0.0004) and
      icodextrin (P = 0.002 and 0.008) were compared with isotonic sodium chloride
      solution. Similarly, there was a significant difference in the volumes recorded
      at 6 h when hypotonic (P < 0.0001) and isotonic sodium chloride solutions (P =
      0.0002) were compared with hypertonic sodium chloride solution. The
      concentrations of chemotherapy in the different carrier solutions varied little.
      The total amount of drug in the peritoneal cavity decreased with all solutions
      and more quickly with 5-fluorouracil than with gemcitabine. There was a
      significant difference in the total intraperitoneal 5-fluorouracil between
      hypotonic and isotonic sodium chloride solutions at 1 h (P = 0.0003) and 3 h (P =
      0.0043), as well as between the isotonic and hypertonic sodium chloride solutions
      at 1 h (P = 0.03) and 3 h (P < 0.0001). Similarly, there was a significant
      difference in the total peritoneal gemcitabine at 6 h between icodextrin and
      isotonic sodium chloride solution (P = 0.01) and between hetastarch and isotonic
      sodium chloride solution (P = 0.05). There were no significant differences in
      plasma 5-fluorouracil and plasma gemcitabine concentrations obtained with the
      five solutions. CONCLUSIONS: These findings show that the clearance of 5
      fluorouracil and gemcitabine from the peritoneal cavity can be significantly
      modified by varying the tonicity or the molecular weight of the carrier solution.
      Peritoneal fluid clearance was slower with hypertonic sodium chloride and high
      molecular weight solutions and this resulted in a reduced clearance of
      chemotherapy. By using a high molecular weight carrier solution the exposure of
      intraperitoneal cancer cells to gemcitabine was prolonged and drug availability
      at the peritoneal surface was increased. Similarly, by using a hypertonic carrier
      solution the exposure to 5-fluorouracil was prolonged and drug availability at
      the peritoneal surface was also increased.

PMID- 11320674
TI  - UFT-induced haemolytic anaemia.
AB  - A case of haemolytic anaemia in a patient under treatment with UFT for metastatic
      colon cancer is reported. Haemolytic anaemia has previously been associated with
      many other chemotherapeutic agents, but not with UFT, an oral anticancer agent
      combining tegafur (Ftorafur, a prodrug of 5-fluorouracil) and uracil.

PMID- 11320675
TI  - Why behavioural genetics is important for psychiatry.

PMID- 11320676
TI  - Why are children in the same family so different? Nonshared environment a decade
      later.
AB  - OBJECTIVE: To review recent developments in the study of nonshared environment;
      that is, the environmental influences that make children growing up in the same
      family different, rather than similar. METHOD: We review several recent
      influential books and papers on the subject of nonshared environment from the
      decade following the 1987 paper that highlighted its importance in psychological
      development. RESULTS: Modest progress has been made toward identifying the
      specific aspects of the environment responsible for nonshared environment.
      Although parents treat their multiple children differently, such differential
      treatment accounts for only a small amount of nonshared environmental influence,
      once genetic factors are controlled. It has been suggested that some degree of
      nonshared environment may be due to the fact that siblings react differently to
      ostensibly shared environmental influences. Peer influence and other experiences
      outside the family may be more important sources of systematic nonshared
      environment. CONCLUSIONS: Despite the difficulties encountered in identifying
      specific sources of nonshared environment, the fact remains that most
      environmental variance affecting the development of psychological dimensions and
      psychiatric disorders is not shared by children growing up in the same family.
      More research and theory are needed to explain why such siblings are so
      different. Chance, in the sense of idiosyncratic experiences, also needs to be
      considered.

PMID- 11320677
TI  - Behavioural-genetic perspectives on personality function.
AB  - In the wake of the recent announcements that the human genome has been mapped,
      efforts to identify the genetic loci underlying personality function will grow
      and intensify. Much research has already been done in this area, but it has for
      the most part been limited to classical biometrical approaches designed to
      determine if personality has a heritable basis. These so-called "heritability"
      studies estimate how much of the individual differences in personality are
      attributable to genetic differences among people. Molecular-genetic approaches,
      on the other hand, are designed to identify specific putative loci, but have
      yielded mixed results. The inconsistency in research findings can be attributed
      in part to the lack of sufficient numbers of genetic markers in the chromosomal
      regions of interest--a problem that the creation of a map of the human genome
      will help to rectify. This map and its inevitable refinements, however, can only
      advance the search for the genes for personality to a limited degree. Serious
      unresolved problems in the conceptualization and definition of personality and
      its dysfunction remain, which will hamper the search for personality genes.

PMID- 11320678
TI  - Community attitudes toward people with schizophrenia.
AB  - OBJECTIVE: We surveyed public attitudes toward people with schizophrenia as part
      of a pilot project for the World Psychiatric Association's Global Campaign to
      Fight Stigma and Discrimination Because of Schizophrenia. METHODS: We conducted
      random-digit telephone surveys with 1653 respondents (aged 15 years or over)
      residing in 2 adjacent rural and urban health regions (71.9% response rate). A
      brief interview collected information on experiences with people with a mental
      illness or schizophrenia, knowledge of causes and treatments for schizophrenia,
      and levels of social distance felt toward people with schizophrenia. RESULTS: One
      half of the sample had known someone treated for schizophrenia or another mental
      illness. Of those able to identify a cause of schizophrenia (two-thirds), most
      identified a biological cause, usually a brain disease. Social distance increased
      with the level of intimacy required. One in 5 respondents thought they would be
      unable to maintain a friendship with, one-half would be unable to room with, and
      three-quarters would be unable to marry, someone with schizophrenia. Those over
      60 were least knowledgeable or enlightened and the most socially distancing.
      Greater knowledge was associated with less-distancing attitudes. When other
      factors were controlled, exposure to the mentally ill was not correlated with
      knowledge or attitudes, even among those who had worked in agencies providing
      services to the mentally ill. CONCLUSIONS: Most respondents were relatively well
      informed and progressive in their reported understanding of schizophrenia and its
      treatment. Clear subgroup differences were apparent with respect to age and
      knowledge. Knowledge of schizophrenia, not exposure to the mentally ill, was a
      central modifiable correlate of stigma.

PMID- 11320679
TI  - Educating the public about mental illness and homelessness: a cautionary note.
AB  - OBJECTIVE: To determine whether the viewing of a video depicting the successful
      struggles of homeless persons with mental illness in finding and maintaining
      housing can have a positive impact on attitudes toward homeless persons with
      mental illness. METHOD: Five hundred and seventy-five high school students
      attending a brief educational session on mental illness participated in 1 of 3
      comparison versions of the 2-hour program (control, video, video plus
      discussion). All completed an "Attitudes toward Homelessness and Mental Illness
      Questionnaire." Demographic and prior exposure variables were entered as a
      covariates in between-group analyses of variance. RESULTS: Females and subjects
      who had more prior encounters with homeless persons were found to have the most
      positive attitudes. After controlling for these effects, the video alone had a
      negative impact on attitudes relative to the other groups, while the video
      followed by a discussion with one of the people featured in it had a largely
      positive impact. CONCLUSIONS: The apparent immediacy and the evocative power of
      video presentations cannot substitute for direct contact for the purpose of
      promoting positive attitude change. The findings are consistent with prior
      research emphasizing the importance of direct interaction with members of
      stigmatized groups to reduce negative attitudes. Education programs trying to
      destigmatize mental illness and homelessness using videos should proceed with
      caution.

PMID- 11320680
TI  - Who develops severe or fatal adverse drug reactions to selective serotonin
      reuptake inhibitors?
AB  - OBJECTIVE: To ascertain the risk factors associated with the development of
      severe and fatal adverse drug reactions (ADRs) or intentional overdoses by
      patients on selective serotonin reuptake inhibitors (SSRIs). METHODS: We
      undertook a data analysis of Health Canada's database of Adverse Drug Reactions
      to SSRIs from 1986 to 1996, as well as a literature review. RESULTS: Among the
      complete ADR reports in the SSRI database, there were no sex differences in
      occurrences of all ADRs (n = 1011), severe ADRs (n = 295), drug-drug interactions
      (n = 312), deaths (n = 87), or intentional overdoses (n = 79), when sex
      differences in prescription practices were considered. There were no differences
      in ADR rates among different SSRIs. The most common cause of death among patients
      taking SSRIs was intentional overdose (n = 65, 74.7%). This was reported in 47
      (72.3%) women and 18 (27.7%) men. The most common drugs taken with SSRIs in
      patients who died of intentional overdoses were benzodiazepines, tricyclic
      antidepressants (TCAs), narcotics, alcohol, and diphenhydramine. Patients who had
      severe or fatal ADRs were more likely to be taking an SSRI with 2 or more other
      drugs, including alcohol. Drug combinations that included another CYP-450 drug
      were especially problematic. A total of 129 cardiovascular ADRs were reported,
      most of which were severe. These included rhythm disturbances, blood pressure
      perturbations, and chest pain or angina. Cardiovascular ADRs most often occurred
      with concomitant drug use of benzodiazepines, TCAs, histamine H2 antagonists,
      lithium, and calcium channel blockers. There were 3 deaths from malignant
      neuroleptic syndrome unassociated with intentional overdose. CONCLUSIONS: SSRIs
      are relatively safe when their widespread use is compared with the prevalence of
      ADRs. SSRIs may, however, be associated with ADRs, and even death, following
      intentional overdose or when taken with 2 or more other drugs or alcohol
      (particularly another drug metabolized by CYP-450). Physicians prescribing SSRIs
      need to consider drug-drug interactions and carefully monitor patients with
      severe affective disorders, comorbid medical conditions (especially
      cardiovascular disease), alcohol abuse, or a history of overdosing.

PMID- 11320681
TI  - Attention-deficit hyperactivity disorder in Manitoba children: medical diagnosis
      and psychostimulant treatment rates.
AB  - OBJECTIVE: To describe physicians' diagnosis rates for attention-deficit
      hyperactivity disorder (ADHD) for children in the province of Manitoba and to
      describe the rate of psychostimulant medication use by these children. METHODS:
      This descriptive study reviewed the computerized administrative records of
      physician visits and prescriptions dispensed to examine a population-based, cross
      sectional cohort of children diagnosed with ADHD or prescribed stimulant
      medication, or both. We found 4787 children with a diagnosis of ADHD over a 24
      month period or a prescription for stimulant medication over a 12-month period,
      or both. Rates were calculated by age, sex, region of residence, neighbourhood
      income level, and physician specialty. RESULTS: Among Manitoba children, 1.52%
      received a medical diagnosis of ADHD and 0.89% received stimulant medication.
      Regionally, diagnosis rates for ADHD varied almost 4-fold, and over 8-fold for
      medications prescribed. Urban areas had higher rates than did rural areas,
      regardless of physician specialty. Diagnosis and prescription rates varied
      according to physician specialty, with the highest rates found among
      pediatricians. An income gradient was evident in rural areas, with rates of ADHD
      diagnosis and medication prescribed increasing with increased neighbourhood
      income level. CONCLUSIONS: The pattern of regional variation found in this study
      suggests that the diagnosis and treatment of ADHD in Manitoba are influenced
      strongly by the practice styles of local physicians.

PMID- 11320682
TI  - Antipsychotic metabolic effects: weight gain, diabetes mellitus, and lipid
      abnormalities.
AB  - OBJECTIVE: To review published and nonpublished literature describing changes in
      weight, glucose homeostasis, and lipid milieu with antipsychotics. METHODS: A
      Medline search was completed using the words weight gain, diabetes mellitus,
      cholesterol, triglycerides, risperidone, clozapine, olanzapine, quetiapine,
      ziprasidone, predictors, prolactin, obesity, and conventional antipsychotics.
      Publications, including original articles, review articles, letters to the
      editor, abstracts or posters presented at professional meetings in the last 4
      years, and references from published articles, were collected. Manufacturers,
      including Eli Lilly Canada Inc, JanssenOrtho Inc, Pfizer Canada Inc, AstraZeneca
      Inc, and Novartis Pharmaceuticals, were contacted to retrieve additional medical
      information. RESULTS: The topic of antipsychotic-induced weight gain is
      understudied, and there are relatively few well-controlled studies. Weight gain
      as a side effect has been described with both conventional and atypical
      antipsychotics. Moreover, some atypical antipsychotics are associated with de
      novo diabetes mellitus and increased serum triglyceride levels. Predictors of
      weight gain may be age, baseline body mass index, appetite stimulation, previous
      antipsychotic exposure, and antipsychotic treatment duration. CONCLUSION:
      Significant weight gain is reported with the existing atypical antipsychotics.
      The weight gain described is highly distressing to patients, may reduce treatment
      adherence, and may increase the relative risk for diabetes mellitus and
      hypertriglyceridemia. Physicians employing these agents should routinely monitor
      weight, fasting blood glucose, and lipid profiles.

PMID- 11320683
TI  - The evolving clinical profile of atypical antipsychotic medications.

PMID- 11320684
TI  - A case of resistant trichotillomania treated with risperidone-augmented
      fluvoxamine.

PMID- 11320685
TI  - Are newer antidepressants really "better tolerated"?

PMID- 11320686
TI  - Gabapentin use in benzodiazepine dependence and detoxification.

PMID- 11320687
TI  - Accelerated weight loss after treating refractory depression with fluoxetine plus
      topiramate: possible mechanisms of action?

PMID- 11320688
TI  - The confidentiality of psychiatric records and the patient's right to privacy.

PMID- 11320689
TI  - Effects of conformation and management system on hoof and leg diseases and
      lameness in dairy cows.
AB  - Foot and leg disorders that result in lameness tend to increase with more
      confined management systems and increased production. Many factors affect hoof
      health, including genetics, conformation, diet, contagious agents, hygiene,
      housing systems, animal behavior, and management. This article describes
      relationships between hoof health and some of these factors as well as methods
      for prevention of lameness on a herd basis.

PMID- 11320690
TI  - Metabolic hoof horn disease. Claw horn disruption.
AB  - Low-quality hoof horn is a frequent underlying cause of lameness in cattle.
      Because the lesions that are observed are the result of insults that affect horn
      production at the cellular level, the term claw horn disruption has been proposed
      to describe the disease process. Although claw horn disruption may result from
      multiple etiologies, the response of the keratinocytes is relatively nonspecific
      in that lesions often appear the same regardless of cause. To solve herd
      problems, the investigation of possible etiologies must be integrated with a
      basic understanding of the anatomic and physiologic features of hoof horn
      production.

PMID- 11320691
TI  - Diseases of the digital soft tissues.
AB  - This article reviews diseases of the digital soft tissues, including digital
      dermatitis, interdigital dermatitis, interdigital phlegmon, and interdigital
      hyperplasia. The clinical signs and diagnosis, epidemiology and pathogenesis,
      etiology, and treatment and prevention of each disease are discussed.

PMID- 11320692
TI  - Surgical treatment of lameness.
AB  - Digital diseases are commonly seen in cattle. Cattle affected by digital
      disorders do not always respond to conservative therapy and require surgery.
      Surgical procedures for the common digital disorders are described, with emphasis
      on the different approaches to the distal interphalangeal joint.

PMID- 11320693
TI  - Antimicrobial issues in bovine lameness.
AB  - This article reviews some of the issues surrounding antimicrobial use in treating
      diseases that cause lameness in cattle. The discussion includes sections on
      selection of an antimicrobial, regimen design, and medication of multiple
      animals. Pathogen susceptibility testing is covered, along with empiric selection
      of antimicrobials. Other issues covered include regional perfusion and topical
      application of antimicrobials, antimicrobials in footbaths and in feed, and
      withdrawal time estimates.

PMID- 11320694
TI  - Investigating herds with lameness problems.
AB  - Many dairy herds have unusual or exceptionally serious lameness problems. Based
      on published observations of risk factors for specific disease problems, along
      with the author's experience, this article describes a systematic way to approach
      and evaluate lameness problems. It is important to define the etiologic diagnosis
      because preventive or corrective measures depend on the cause of the herd
      problem. Compound etiologies and complex risk factor interactions are the norm in
      this sometimes frustrating endeavor.

PMID- 11320695
TI  - Lameness in feedlot cattle.
AB  - This article examines the various causes of lameness in feedlot cattle, with an
      emphasis on clinical signs, treatment, and prevention. Specific conditions are
      discussed, including interdigital necrobacillosis, laminitis, feedlot injuries,
      and feedlot lameness associated with Mycoplasma bovis. Immune management of the
      foot is also reviewed.

PMID- 11320696
TI  - Prevention of lameness in cow-calf operations.
AB  - Lameness is a significant cause of economic loss, premature culling, and loss of
      genetics in cow-calf operations. In recent years, attention to treatment and
      prevention of lameness has increased. Veterinarians must be aware of factors
      associated with lameness such as genetics, environment, and nutrition so that
      preventive measures can be instituted in consultation with ranchers.

PMID- 11320697
TI  - Anatomy of the distal limb.
AB  - A detailed knowledge of anatomy is essential to understand the various pathologic
      processes and to perform different surgical techniques involving the limbs of
      cattle. This article reviews macroscopic anatomy of the distal limb, muscle
      tendon units, neurovascular anatomy, and external and microanatomy of the claw.

PMID- 11320698
TI  - Lameness examination in cattle.
AB  - Veterinarians are often asked to examine cattle for lameness. A good history,
      observation of stance and stride, and physical examination are critical to the
      diagnosis of lameness in cattle. Methods of examination, including observation of
      the animal at a distance and during movement, are described. Lameness grading
      systems and ancillary diagnostic tests are also discussed.

PMID- 11320699
TI  - Functional and corrective claw trimming.
AB  - Foot care and claw trimming require proper systems for restraint, sharp knives
      and trimming equipment, and an understanding of the biomechanics of weight
      bearing and hoof overgrowth in cattle. The objective of functional claw trimming
      is to correct hoof overgrowth, thereby re-establishing appropriate weight bearing
      within and between the claws of each foot. Traditional trimming methods fail to
      achieve these objectives. Corrective trimming procedures are applied to horn
      lesions affecting the claw capsule. Primary objectives of corrective trimming are
      to adjust weight bearing to provide rest for diseased claws and to remove loose
      horn and hard ridges that may cause further injury to the corium. The application
      of a foot block to the healthy claw is a valuable aid in foot care when
      corrective trimming alone is insufficient to provide needed relief from weight
      bearing. Finally, the use of topical treatments under a bandage is controversial.
      It is recommended that caustic treatments be avoided and that the use of a
      bandage be limited to conditions requiring hemostasis or when operators are
      committed to their removal within a period of 2 to 5 days depending on the level
      of environmental contamination.

PMID- 11320700
TI  - Abnormalities of hoof growth and development.
AB  - The normal development of the horn capsule (epidermis), with its dermal support
      (corium), is described. Abnormalities of horn growth may be caused by changes in
      blood flow (laminitis), the biomechanics of weight bearing, heritable
      developmental conditions, and other changes of unknown cause.

PMID- 11320701
TI  - Sand cracks, horizontal fissures, and other conditions affecting the wall of the
      bovine claw.
AB  - The wall of the bovine claw is created only by the dermis beneath the coronary
      band. Keratogenic tissues in this region are susceptible to nutritional changes
      or stress, which changes the characteristics of the horn produced. Horizontal
      grooves or fissures result that weaken the claw wall and are instrumental in
      generating many vertical fissures. The rate at which the claw grows can be used
      to calculate the date of a nutritional insult.

PMID- 11320702
TI  - A case of lichenoid purpura possibly caused by diltiazem hydrochloride.
AB  - A 65-year-old Japanese man presented with itchy purpuric lichenoid papules of six
      months' duration on his legs and buttock. A topical glucocorticoid ointment was
      not effective. The biopsy specimen histologically showed a dense lichenoid
      infiltration of lymphocytes and histiocytes into the dermoepidermal junction; red
      blood cells were seen in the infiltration. Based on the clinical and pathological
      findings, we diagnosed this case as lichenoid purpura of Gougerot-Blum. The
      lesions disappeared when the diltiazem hydrochloride that he had been taking was
      discontinued.

PMID- 11320703
TI  - Pedunculated basal cell epithelioma which is not Pinkus tumor.
AB  - A 33-year-old female with pedunculated basal cell epithelioma was reported. She
      had noticed a cutaneous tumor on the scalp for two years before admission. It
      developed gradually and clinically resembled fibroma or pigmented nevus. Total
      resection was performed, and its histopathology revealed the solid or cystic type
      of basal cell epithelioma.

PMID- 11320704
TI  - A linear erythema on the nose of a Korean girl.

PMID- 11320705
TI  - Kerion celsi in an infant treated with oral terbinafine.

PMID- 11320706
TI  - A papillary carcinoma: cutaneous metastases from lung cancer.

PMID- 11320707
TI  - About the paper "Elephantiasis neuromatosa and Becker's melanosis" (J Dermatol,
      26: 396-398, 1999).

PMID- 11320708
TI  - Distribution density of intraepidermal nerve fibers in normal human skin.
AB  - A total of 74 specimens was obtained from the normal human skin of patients from
      3 to 90 years old. The specimens were roughly classified into 5 groups: 15 for
      the face group from the face; 15 for the abdomen group from the abdomen; 13 for
      the back group from the back; 14 for the arm group from the upper arm and
      forearm; and 17 for the leg group from the thigh and lower leg. They were all
      fixed in 4% paraformaldehyde and 14% saturated picric acid. Cryostat sections
      were examined by the immunoperoxidase method and indirect immunofluorescence
      (IF). Primary antibodies against neurofilament, neuron-specific enolase, protein
      gene product 9.5 (PGP 9.5) and S-100 protein were used. The most effective method
      was found to be the combination of IF with PGP 9.5; it visualized the
      intraepidermal nerve fibers easily and clearly. Of the 74 specimens, 32 (43%) had
      intraepidermal PGP 9.5-immunoreactive (or nerve) fibers (IPIF), and 42 (57%) did
      not have any. With reference to the different skin locations, the maximal rate of
      specimens having IPIF was 57% in the arm group, and the minimum was 23% in the
      back group. IPIF positive specimens had approximate surface lengths of 6 mm, in
      which the existence number of the IPIF was 1 to 75. Their distribution density
      per 1000 epidermal basal cells was highest at 9.63 in the arm group and lowest at
      2.89 in the back group. Their thickness was 2.94 +/- 0.83 microns with no
      significant differences among the five groups. We concluded that intraepidermal
      nerve fibers may not be distributed evenly in the hairy portions of normal human
      skin, but they may be present focally. Physiologically, two-point discrimination
      of itch may be explained by the distribution mode of intraepidermal nerve fibers.

PMID- 11320709
TI  - Churg-Strauss syndrome with renal involvement: a case report.
AB  - We report a case of Churg-Strauss syndrome with renal involvement. A 51-year-old
      woman was admitted to our hospital in April of 1999 complaining of abdominal pain
      and severe diarrhea followed by multiple purpura on both legs. A diagnosis of
      Churg-Strauss syndrome was made on the basis of the presence of preceding asthma,
      eosinophilia, increased IgE, and the histological findings of a biopsy taken from
      the purpura. Creatinine clearance level at admission was low (43.3 ml/min) and
      urinalysis revealed proteinuria and microscopic hematuria. These abnormalities
      were improved with systemic steroid therapy. Renal involvement seems to be more
      common than previously reported in Churg-Strauss syndrome.

PMID- 11320710
TI  - Grouping prurigo: report of cases.
AB  - Grouping prurigo was reported as a new clinical entity by Ofuji et al. in 1977
      and 1988. No further cases have been reported since. Herein we report four cases
      of grouping prurigo and discuss the possible relationship between this condition
      and other diseases in the prurigo group, including chronic pruritic papular
      dermatitis in adult men, which was reported by Chang et al. in 1999. Since
      grouping prurigo and chronic pruritic papular dermatitis in adult men share
      approximately the same characteristics in both clinical and histopathological
      findings, we concluded that these two disorders may be the same entity,
      characterized by grouped pruritic solid papules on the trunk.

PMID- 11320711
TI  - Disseminated superficial actinic porokeratosis with both typical and prurigo
      nodularis-like lesions.
AB  - We report a 50-year-old Korean patient who developed a disseminated superficial
      actinic porokeratosis (DSAP) with two types of lesions. One was a typical DSAP
      lesion clinically and histopathologically. The other was clinically similar to
      prurigo nodularis, but histologic examination showed the findings of
      porokeratosis such as cornoid lamellae and loss of the granular layer in addition
      to those of chronic lichenified dermatitis, so it could be described as prurigo
      nodularis-like porokeratosis. The nodular lesions seemed to develop on
      preexisting typical lesions of DSAP mainly during the summer by the aggravation
      of pruritic symptoms and scratching associated with sun exposure. Although we
      could not find any published reports describing lesions like those of our case,
      we think that such prurigo nodularis-like porokeratosis can develop in patients
      with DSAP in some situations involving pruritus and scratching.

PMID- 11320712
TI  - Sarcoidosis associated with psoriasis vulgaris.
AB  - We report a 70-year-old patient with sarcoidosis associated with psoriasis
      vulgaris. He had a nodule on the medial lower lid of his right eye. Oral
      corticosteroid for the sarcoid lesions and oral PUVA for psoriasis were employed.
      The cutaneous lesion disappeared within two months after starting the therapy. No
      relapse of sarcoidosis has been seen for eight years. The association of
      sarcoidosis with psoriasis has been previously reported; however, it is still
      unclear whether this association coincidental or meaningful.

PMID- 11320713
TI  - Malignant melanoma cells in the eccrine apparatus.
AB  - A case of malignant melanoma arising on the sole of a 75-year-old Japanese man is
      presented. Histopathologically, in addition to the intraepidermal and intradermal
      malignant melanoma cells reaching the upper part of the dermis, cells were also
      found in the deep part of the ductal epithelium of the eccrine apparatus.
      Melanoma cells, and melanocytic nevus cells as well, are rarely found within the
      epithelial structure of sweat glands, yet they are frequently found in that of
      hair follicles. In order to avoid a residue of melanoma cells in the deep part of
      the eccrine apparatus, a fairly deep excision should be performed even for this
      melanoma.

PMID- 11320714
TI  - A case of cutaneous disseminated sporotrichosis.
AB  - We described a case of cutaneous disseminated sporotrichosis. The condition was
      diagnosed based on isolation and identification of Sporothrix schenckii from the
      lesions. The patient was otherwise normal, including a negative HIV test. The
      blood culture did not grow S. schenckii. However, spores were detected in the
      biopsy histological sections and stained positively with PAS staining and ConA
      and LCA lectin histochemistry.

PMID- 11320715
TI  - [Alcohol concentration in the coronary sinus after transarterial ablation of
      septal hypertrophy in hypertrophic obstructive cardiomyopathy].
AB  - BACKGROUND AND OBJECTIVE: The size of the resulting myocardial necrosis varies
      after percutaneous transarterial ablation (PTA) of hypertrophied septum in
      patients with hypertrophic obstructive cardiomyopathy (HOCM). It was the aim of
      this study to discover whether the alcohol concentration in coronary sinus (CS)
      blood is a useful and appropriate parameter and what conclusions can be drawn
      from it. PATIENTS AND METHODS: PTA was done in four patients (two women and two
      men, aged 30-53 years) with HOCM. Before the intervention the gradient across the
      left ventricular outflow tract ranged form 20 to 80 mmHg, postextrasystolic it
      ranged from 40 to 180 mmHg. 1 x 2 ml ethanol was injected into the first septal
      branch in 3 patients, 2 x 2 ml in one. The alcohol concentration in coronary
      sinus blood was measured every 30 sec for up to 5 min before and after ablation.
      The amounts were compared with the size of the akinetic area in the
      echocardiogram and the maximal value of creatine kinase, as a measure of the size
      of myocardial necrosis. RESULTS: The left ventricular outflow gradient was
      reduced in all patients, to 0-30 mmHg and postextrasystolic to 30-90 mmHg. A
      pacemaker had to be implanted in one patient who developed a 3 degrees AV block.
      The alcohol concentration in coronary sinus blood ranged from maximally 1.53 and
      0.23 per thousand after 30 sec and then fell to 0.56-0.12 per thousand after 5
      min. The patient with the highest CS alcohol concentration also had the highest
      maximal value for creatine kinase (68 mumol/l) and the largest akinetic area in
      the echocardiogram. CONCLUSION: The extent of myocardial necrosis can probably be
      estimated from the CS blood concentration of alcohol after alcohol ablation. If,
      after the first injection, high alcohol concentrations are measured, further
      alcohol injections are not indicated.

PMID- 11320716
TI  - [German Health survey 1997/98: immune status against poliomyelitis].
AB  - BACKGROUND: One of the goals of the WHO is the worldwide eradication of
      poliomyelitis in the next years. A high level of population immunity protects
      against imported wild viruses from endemic areas. PATIENTS AND METHODS: The first
      German Health Survey, a representative study of the health status of the
      population (aged between 17 and 79 years) in unified Germany, was started in
      1997. In order to study the serological status against poliomyelitis, a
      representative serum panel was investigated (n = 2564). Furthermore, 881 sera
      from persons aged less than 18 years were included in the study. The
      microneutralization test was used to demonstrate antibodies against the three
      poliovirus types. For the first time, the results were expressed in International
      Units. The threshold values 0.075 IU, 0.180 IU, 0.080 IU were calculated for
      Polio 1, 2, 3 respectively. RESULTS: Overall, neutralizing antibodies against
      poliovirus type 1, 2 and 3 were detected in 96.2%; 96.8% and 89.6% of samples,
      respectively. 85% of test persons had antibodies against all three virus types.
      CONCLUSIONS: The seroprevalence of antibodies against all three types of
      polioviruses indicates a very high population immunity. It must be kept after the
      switch of immunization strategy from attenuated to inactivated vaccine in Germany
      (OPV to IPV).

PMID- 11320718
TI  - [Chylous cyst of the mesentery].

PMID- 11320717
TI  - [Antiphospholipid antibody syndrome as the cause of clinical rapidly progressing
      vasculopathy].
AB  - HISTORY AND ADMISSION FINDINGS: For 3 weeks a 54-year-old man had been
      unsuccessfully treated with antibiotics for ulcerating tonsillitis with fever,
      weight loss, occasional headaches, and hypertension. A year before he had
      suffered a transitory cerebral ischaemic attack. On admission he had a fever of
      38.6 degrees C, blood pressure of 185/100 mmHg and a nonspecific 2/6 apical
      systolic murmur. INVESTIGATIONS: Erythrocyte sedimentation rate was 100/120 mm, C
      reactive protein 1.5 mg/dl, serum creatinine 2.45 mg/dl, urinary protein 0.8 g/d.
      Tests for antinuclear antibodies (ANCA) against neutrophil granulocytes and for
      native DNA antibodies were negative, as were serological tests for Coxsackie
      virus, Cytomegalovirus and Epstein-Barr virus. Sonography and computed tomography
      revealed thrombosis along the entire aortic wall, renal artery stenosis and a
      contracted left kidney. Transoesophageal echocardiography demonstrated small
      thrombi on the aortic valve leaflets. Coloscopy showed ulcerative colitis.
      TREATMENT AND COURSE: The patient was anticoagulated. Local cold produced livedo
      reticularis. Tests for cardiolipin antibodies in serum and a skin biopsy provided
      the diagnosis of antiphospholipid antibody syndrome (APS). As the skin biopsy
      showed vasculitis, immunosuppressive treatment was started. This stabilized the
      condition and he was discharged to be followed by his general practitioner.
      CONCLUSION: APS can cause complex symptoms in many organs, but effective
      treatment (anticoagulation, corticosteroids, immunosuppressives) is available, as
      this case demonstrates.

PMID- 11320719
TI  - [Furosemide].

PMID- 11320720
TI  - [Early summer meningoencephalitis in low risk areas].

PMID- 11320721
TI  - [Erythropoietin--use in hematologic oncology and radiotherapy].

PMID- 11320722
TI  - [Dosage and monitoring of tacrolimus after kidney transplantation].

PMID- 11320723
TI  - [Lactose intolerance].

PMID- 11320724
TI  - [Risks and views on responsibility in the medical profession].

PMID- 11320725
TI  - The MNSs blood group system in the population of South Backa.
AB  - Blood groups represent qualitative characteristics of humans which are controlled
      by one or a few genetic loci and due to this it is easy to determine various
      kinds of alleles and their frequencies in certain samples. Analyzing variability
      of characteristics such as blood groups, it is possible to get an insight in
      genetic structure of a population and it represents a suitable manner for
      detecting similarities and differences between populations. The intention of this
      study was to determine the genetic structure of the population of South Backa in
      a classic manner by phenotypic characteristics in MNSs blood group system, to
      assess frequencies of alleles, phenotypes, genotypes, allelic frequencies and
      genetic distances between the population of South Backa and populations of
      various geographic regions. Immunohematologic investigation of 1.000 persons
      included blood group testing in the MNSs system, which was a basis for applying
      population-genetic analysis based on Hardy-Weinberg equilibrium in populations.
      Results of investigation revealed that in population of South Backa, s allele has
      the highest frequence (85.59%); the most frequent genotypes are ss (48.5%), MN
      (43.4%), Ss (37.4%); the most frequent phenotypes are MNss (19.3%), MNSs (18.4%)
      and NNss (15.3%). Genetic distances between populations are greatest among
      geographically most distant populations as Eskimos, Australian Aborigines,
      populations of Papua-Gvinea, Fiji and low in populations of Turkey, Italy,
      Albania and Cyprus.

PMID- 11320726
TI  - [Use of nasogastric intubation in laryngeal surgery].
AB  - INTRODUCTION: This article reviews postoperative feeding in 173 patients after
      total laryngectomy, pharyngolaryngectomy or functional partial laryngectomy.
      Nasogastic feeding-tube was used in all patients except those with chordectomy
      and there was a follow-up of average recovery time of the swallowing function in
      all operated patients. RESULTS: We compared effects of feeding, from the 4th
      postoperative day, via nasogastric tube and orally--without tube on appearance of
      pharyngocutaneous fistula in laryngectomized patients. Average time of appearance
      of fistula in total laryngectomies was 9.3 days, in pharyngolaryngectomies 9.7
      days. The average length of feeding via nasogastric tube was 11.2 days in the
      first and 11.7 days in the second group, indicating that fistula appeared at the
      time of nasogastric tube-feeding, or that the tube did not prevent appearance of
      fistula. In horizontal supraglottic laryngectomy and subtotal laryngectomy
      nasogastric tube-feeding is necessary in the first 7 to 10 postoperative days.
      DISCUSSION AND CONCLUSION: When starting peroral feeding it is necessary to take
      out the tube due to changes it caused on laryngcal mucosa that can prolong the
      period of swallowing recovery. In vertical partial laryngectomy nasogastric tube
      is not necessary and peroral feeding can start from the 4th postoperative day. If
      we compare pharyngolaryngectomy and other kinds of laryngeal operations, the
      greatest body weight loss occurred in horizontal supraglottic laryngectomy p <
      0.05 and subtotal laryngectomy p < 0.05.

PMID- 11320727
TI  - [Free oxygen radiacals and kidney diseases--part I].
AB  - ADVERSE EFFECTS OF OXYGEN: Adverse effect of oxygen on anaerobes implies
      oxidation of the basic cell constituents NAD(P)H, thiols, iron-sulphur proteins,
      pteridines and others) and inactivation of the essential components of the active
      site of enzymes. Oxygen can also adversely affect the aerobes, especially if long
      term influence is taken into consideration, while exposition to high-pressure
      oxygen causes considerable damages. Direct influence of oxygen on aerobes due to
      slow and limited enzyme inactivation (for example glutamate decarboxylase) and
      small number of affected "targets" is not responsible for total adverse effects
      of oxygen. Even in 1954 it was supposed that oxygen free radicals are the most
      responsible for the adverse effects of oxygen. ATMOSPHERIC (TRIPLET) OXYGEN:
      Electron configuration of triplet oxygen explains its reactivity since it is a
      biradical. The reactions of oxygen with non-radicals are possible with
      participation of transition metals (except zinc), while its reactivity is much
      more expressed in case of reactions with other radical species. ACTIVE OXYGEN:
      More reactive forms of oxygen, known as singlet oxygen, can be generated by an
      input of energy to triplet oxygen. Singlet-oxygen is obtained mainly by
      photoexcitation in the presence of initiators (methylene blue, chlorophyll etc.)
      and as a product of reactions of ozone with certain biomolecules. REDUCED FORMS
      OF OXYGEN: If a single electron is added to the triplet oxygen, it must enter one
      of the antibonding molecular orbitals and produce the superoxide radical--(O2.-).
      Addition of one more electron produces peroxide ion--O2(2-), which forms hydro
      peroxide in presence of H+, the most common two-electron reduction product of
      oxygen in biological systems. The four-reduction product of oxygen in biological
      systems is water. SUPEROXIDE RADICAL: The in vivo production of superoxide
      radical is possible in many different ways mentioned in this paper. This radical
      species is unstable in water solutions because of dismutation reaction leading to
      non-enzymic generation of hydroperoxide. The most reactive radical species-
      hydroxyl radical is produced from hydro peroxide by Fenton or Haber-Weiss
      reactions in the presence of catalytic transition metals (iron or copper).
      HYDROXYL RADICAL: Hydroxyl radicals are the most reactive radical species. The
      way of their generation has been shown in detail in this paper with special
      emphasis given to Fenton and Haber-Weiss reactions, that is, transition metals
      (iron and copper) as catalizators for these reactions. The reactivity of hydroxyl
      radical can be recognized by monitoring the second-order rate constants for
      reactions of the hydroxyl radical with some organic compounds in aqueous solution
      presented in this paper. Although the number of compounds that can be affected
      and damaged by hydroxyl radicals is great, until now, attention has been paid
      mostly to investigation of attacks of these radical species on lipids, proteins
      and DNA. LIPID PEROXIDATION: Radicals react with lipids and cause oxidative
      destruction of unsaturated, that is, polyunsaturated fatty acids, known as lipid
      peroxidation. Both lipids in biological systems and lipids as food constituents
      are submitted to this process. Lipid peroxidation is a chain reaction and its
      mechanism has been shown in detail in this paper. Lipid peroxidation in cells
      leads to direct damage of cell membranes with indirect damages of other cell
      constituents, caused by reactivity of secondary products of this reaction,
      aldehydes. This complex reaction is responsible for damages of many tissues and
      progress of some diseases (atherosclerosis). OXIDATIVE STRESS: Protection of an
      organism from oxygen free radicals implies activity of enzymatic (catalase, SOD,
      glutathione peroxidase, glutathione reductase etc.) and nonenzymatic (vitamin E.
      vitamin C. glutathione, uric acid etc.) systems of protection. Disturbance of the
      balance between production of oxygen free radicals (or some other radical
      species) and activity of antioxidative system of protection causes the so called
      oxidative stress. An organism can tolerate a mild oxidative stress but a higher
      disturbance between the production of free radicals and the activity of the
      antioxidative protection results in lipid protein and DNA as well as numerous
      diseases.

PMID- 11320728
TI  - [Ovarian Leydig cell tumor].
AB  - INTRODUCTION: Leydig cell tumors are sex cord-stromal tumors with sexual steroid
      production (predominantly testosterone). They account for less than 0.6% of
      ovarian neoplasms and mostly appear at the age of 28. HISTOPATHOLOGY: It is a
      solid yellowish nodular tumor, less than 5 cm in diameter. It consists of
      polygonal Leydig cells, eosinophillic cytoplasm with lipid vacuole and lipochrome
      pigments. Nuclei are oval, pleomorphic with rare nucleoli. Hyperthecosis is
      around the tumor. CASE DESCRIPTION: Signs and symptoms depend on age of women and
      testosterone levels. Women complain about hirsutism, hoarseness, muscular
      hypertrophy, increased libido, clitoromegaly, temporal hair loss and menstrual
      disturbances. DIAGNOSIS: Basal hormone analysis reveals extremely high
      testosterone levels, mildly high androstenedione and 17 OH progesterone, and
      suppressed follicle stimulating hormone and luteinizing hormone. Estradiol,
      dehydroepiandrosterone sulfate and other hormones are normal. Dexamethasone
      screening test decreases dehydroepioandrosterone sulfate and androstenedion,
      whereas testosterone levels are only partly suppressed. Human choriogonadotropin
      test is clearly stimulatory for testosterone. Suppressed gonadotropin levels do
      not respond to luteinizing hormone releasing hormone stimulation.
      Ultrasonography, nuclear magnetic imaging, Doppler sonography, ovarian vein
      catheterization can be used for visualization. The removal of tumor is followed
      by normalization of testosterone levels, increase of gonadotropins and gradual
      disappearance of all symptoms and signs. THERAPY: The only effective therapy is
      operative.

PMID- 11320729
TI  - [New views on the physiology of wound healing].
AB  - INTRODUCTION: A great deal of progress has been made in the last few decades in
      understanding the cellular and biochemical interplay that comprises the normal
      wound healing response. This response is a complex process involving intricate
      interactions among a variety of different cell types, structural proteins, growth
      factors and proteinases. PHASES OF WOUND HEALING: Acute wounds maturate through
      phases of coagulation, inflammation, matrix synthesis and deposition,
      angiogenesis, fibroplasia, epithelialization, contraction and remodelling, but
      three classic phases of wound healing are inflammation, fibroplasia and
      maturation. DERMAL FIBROPROLIFERATIVE DISORDERS: Two main forms of
      fibroproliferative disorders are hypertrophic scars and keloids. These disorders
      are characterized by an overabundance of wound collagen through overproduction of
      collagen or impaired degradation of collagen. Hypertrophic scars are raised,
      pruritic and edematous lesions that do not exceed the margins of the original
      wound (in contrast to keloids). Histologically, these lesions are
      indistinguishable and are characterized by thick, hyalinized collagen bundles
      arranged in nodules. The degree of hypertrophic scarring is believed to be
      related to the duration of time during which the wound is allowed to remain in
      inflammatory phase of healing. Wound closure tension may also play a role by
      altering the intracellular cytoskeletion of fibroblasts and increased secretion
      of TGF-beta and cytokines. CONCLUSION: Healing of chronic cutaneous wounds is
      still a great problem of modern society--huge costs, impaired quality of life. In
      the last few decades a great progress was made in understanding the cellular and
      biochemical interplay.

PMID- 11320730
TI  - Incidence of cerebral dysfunction as a parameter for decision making in the
      management of preterm labor.
AB  - The study presents a retrospective analysis of the data on pregnancy, delivery
      and cerebral dysfunction in 296 premature infants of singleton pregnancies, body
      weight > 1000 g, delivered at the Department of Obstetrics and Gynaecology in
      Novi Sad during 1997. Preterm newborns are exposed to a high risk of perinatal
      pathology, with 66.55% newborns from pathological course of pregnancy. Vaginal
      delivery--vertex presentation was registered in 69.93%, breech presentation in
      6.41% and cesarean section in 23.65%. The preterm children have lower Apgar
      Scores and umbilical artery Ph values than term children. Cerebral dysfunction
      was diagnosed in 32.09%, whereas the incidence is inversely proportionate to
      gestational age and body weight at birth. The mode of delivery does not
      significantly affect cerebral dysfunction (p < 0.05) which means that intrapartal
      trauma is not a frequent cause of cerebral distress of preterm newborns. The
      labor occurring before the 34th gestational week can be performed vaginally if
      the fetus is either in vertex or complete breech presentation, if the course of
      labor is regular and cardiotocography findings within physiologic values.

PMID- 11320731
TI  - [Nutritional status of children in the North Backa Region based on the body mass
      index].
AB  - INTRODUCTION: Monitoring nutritional status of children at a population level
      represents an important index of the nutritional quality and quantity in a
      certain period of time. The aim of this paper was to determine the body mass
      index (BMI kg/m2) and evaluate the nutritional status of children in the North
      Backa Region (Subotica, Backa Topola and Mali Idos). MATERIAL AND METHODS: A
      transversal anthropometric study examining body weight and height during a mass
      screening of children in Health centers in the North Backa Region, 25.790
      children aged 1-18 have been examined in the period 1995-1998. Evidence and
      statistical evaluation of data have been processed using the software "CHILD"
      determining the percentile values of BMI and nutritional status according to
      reference values of the First National Healts and Nutrition Examination Survey
      (NHANES 1). RESULTS: Analyzing the nutritional status of children aged 6-18 in
      the North Backa Region we found 4.39% boys and 5.41 girls with BMI < P5 as
      underweight, moderate underweight with BMI P5-15 were 7.28% boys and 6.96% girls,
      whereas normal nutritional status (BMI P15-85) was found in 67.13% boys and
      67.25% girls. 12.77% of boys and 11.78% of girls were overweight (BMI P85-95) and
      obesity (BMI > P95) was registered in 8.46% boys and 8.60% girls. Using the same
      software and based on results for the whole group of children aged 1-18,
      reference values were calculated for BMI as a regional reference data which can
      be used in everyday public health setting. DISCUSSION: This research is the first
      examination of the nutritional status of children at a population level in the
      North Backa Region in regard to BMI. This model of nutritional status monitoring
      in children using the above mentioned software will be used at a national level.
      CONCLUSION: These results show an inadequate nutritional status of children in
      the North Backa Region which can be associated with unbalanced nutrition and life
      style. Therefore, permanent monitoring of the nutritional status in children has
      been established in order to take adequate preventive measures to realize
      nutrition of children and adolescents.

PMID- 11320732
TI  - [Radiochemical purity and stability of Tc-99m-pyrophosphate].
AB  - INTRODUCTION: In vitro stability of 99mTc-radiopharmaceuticals is an important
      parameter of quality. In the paper the shelf-life of the bone-seeking
      radiopharmaceutical 99mTc(Sn)-pyrophosphate was examined under different
      experimental conditions. MATERIAL AND METHODS: The solution of pyrophosphate was
      prepared and dispensed into 2-ml fractions which were kept at-20 degrees C. In
      different time intervals the samples were thawed and labeled. The in vitro
      stability of labeled preparation was examined on the unprotected and the samples
      protected by nitrogen purge or by addition of solutions of ascorbic or genetisic
      acid of known concentrations. The content of 99mTc-pertechnetate was determined
      by paper chromatography. RESULTS AND DISCUSSION: In comparison with unprotected,
      samples protected by nitrogen purge exhibit better, but not satisfactory
      stability. Best results are obtained by using chemical stabilizers. The presence
      of 50-60 micrograms/ml of ascorbic acid keeps the content of 99mTc-pertechnetate
      below 5% during six hours even in solutions of high initial radioactive
      concentrations (up to about 814 MBq/ml). With this concentration of ascorbic
      acid, good results are obtained also by labeling inactive solutions kept at low
      temperatures during seven days. Genetisic acid is also efficient but its
      concentration should be about ten times higher. CONCLUSION: The in vitro
      stability of 99mTc(Sn)-pyrophosphate depends on the initial radioactive
      concentration of 99mTc and time after labeling. Best results were obtained when
      the preparation contained ascorbic acid as a chemical stabilizer. Its
      concentration in the range of 50-60 micrograms/ml is sufficient to keep the
      content of 99mTc-pertechnetate below 5% during six hours, both in freshly
      prepared samples and those kept at low temperatures for seven days.

PMID- 11320733
TI  - [Anesthesia for thymectomy in patients with myasthenia gravis].
AB  - INTRODUCTION: Anesthetic approach to patients with myasthenia gravis requires
      preoperative treatment with anticholinesterase drugs, corticosteroids,
      plasmapheresis and mechanical ventilation support, either before or immediately
      after the surgical procedure. MATERIAL AND METHODS: During the period of 10
      years, 41 patients with myasthenia gravis (71.42% female and 28.57% male, aged
      between 9 and 69 years) underwent surgical procedures. All the patients were
      preoperatively treated with anticholinesterase drugs and corticosteroids and were
      in remission. Considering the fact that barbiturates and succinylcholine should
      be avoided during induction of anesthesia, halothane was used. The induction into
      the surgical stage of anesthesia was pronged. RESULTS: Intubation, as well as the
      surgical procedure, were successfully completed in all patients. All, except
      three patients, started breathing spontaneously. Two patients required
      respiratory support during the immediate postoperative period and one patient
      died. After the surgical procedure one patient had manifested gastrointestinal
      bleeding and three patients had pneumothorax (one iatrogenic and two during
      mechanical ventilation). Mechanical ventilation in postoperative period indicates
      inadequate respiratory function in patients with myasthenia gravis, whereas
      thymectomy is a therapy of choice. Volatile inhalation anesthetic with pre and
      postoperative anticholinesterase drugs and corticosteroids resulted in complete
      remission.

PMID- 11320734
TI  - [Emergency contraception].
AB  - INTRODUCTION: The aim of this study was to point to the significance of emergency
      contraception following unsafe sexual intercourse. This method of contraception
      has been in use since the middle sixties, although in our country it is not
      applied very often. Indications for emergency contraception comprise every woman
      who experiences contraceptive failure or those not using any common contraception
      for any reason. MATERIAL AND METHODS: Emergency contraceptive devices are most
      often applied either in combination with estrogen and progesterone or only
      progesterone in high dosage (0.25 mg levonorgestrel and 50 mg ethinyl-estradiol)
      during 72 hours after the intercourse and a repeated dose 12 hours later.
      CONCLUSION: Emergency contraception is recommended as a single procedure. If used
      several times during a year, the risk of unwanted pregnancy increases. The
      mechanism of effect of emergency contraception depends on the timing during
      menstrual cycle; it can prevent ovulation, fertilization or implantation.
      Emergency contraception does not cause abortion and it is not effective if the
      process of implantation has started. Unwanted side-effects are not known.

PMID- 11320735
TI  - [Histiocytic necrotizing lymphadenitis (Kikuchi-Fujimoto disease)].
AB  - INTRODUCTION: Histiocytic necrotizing lymphadenitis is a disease of unknown
      etiology, favourable course and outcome, mostly encountered in young women. It
      exhibits increased temperature and lymphadenopathy. The illness resolved
      spontaneously after a few months. A CASE REVIEW: In a 32-year-old patient the
      disease developed gradually, with pain in the right axilla, within enlarged
      lymph. Two weeks later, her temperature increased to 39 degrees C, accompanied by
      fever, shivering, malaise and loss of appetite. The ultrasonographic finding
      showed a conglomerate of hypoechogenic lymph nodes, with a few enlarged lymph
      glands. By immunohistochemical examination of a gland tissue sample the diagnosis
      was established Kikuchi-Fujimoto disease ("Histiocytica necrotizing
      lymphadenitis"--"Apoptotic lymphadenitis"). Corticosteroid therapy had been
      administered for one year, which resulted in both subjective improvement and
      regression of enlarged lymph nodes. DISCUSSION: A connection between this disease
      and viruses has not been proved. Presence of intracellular tubuloreticular
      formations suggests autoimmune etiology of histiocytic necrotizing lymphadenitis.
      It is considered as hyperimmune reaction of the organism induced by a viral
      infection. Differential diagnosis should consider taxoplasmosis, tuberculosis,
      lymphadenitis and malignant lymphoma. CONCLUSION: Although histiocytic
      necrotizing lymphadenitis is a rare disease, this case shows that it should be
      considered when lymphadenopathy, particularly cervical, occurs in young women,
      accompanied by increased temperature.

PMID- 11320736
TI  - [Von Recklinghausen's neurofibromatosis (neurofibromatosis type I)--a familial
      case report].
AB  - INTRODUCTION: Neurofibromatosis is a term used for two disorders: NF-1 and NF-2.
      NF-1 is Von Recklinghasusen's neurofibromatosis and comprises characteristic skin
      lesions (cafe au lait spots, intertriginous freckles, neurofibromatous skin
      tumors) and other congenital and hamartomatous bone, endocrine glands and central
      nervous system lesions. Its incidence is one in every 2500 to 3300 births. CASE
      REPORT: Two female patients, a 20 years old daughter and her mother 46 years of
      age were admitted to the Clinic of Dermatovenereology in Novi Sad due to
      appearance of many sessile and pedunculated neurofibromas, cafe au lait spots and
      freckles on their trunks, axillary and inguinal regions. Laboratory findings
      showed no abnormalities. Both of them were examined by many specialists. No
      systemic disturbances were established. The daughter was sent to plastic surgery
      for operative treatment. DISCUSSION: The clinical presentation of NF-1 is very
      variegated. Beside characteristic skin lesions, other clinical features include
      skeletal bony abnormalities, mental deficiency, seizures, neurofibromas of the
      spinal and cranial nerve roots, iris hamartomas, optic nerve gliomas, endocrine
      disorders, endocrine tissue tumors, other visceral tumors, etc. Some of these
      disorders can be life-threatening. Malignant transformations of the NF-1 lesions
      occur approximately in 5% of patients, most often as neurofibrosarcomas, Wilms'
      tumors, rhabdomyosarcomas or various forms of leukemias. CONCLUSION: We present
      familial cases of Von Recklingausen's neurofibromatosis without systemic
      abnormalities so far. The clinical course of this disease is unpredictable and a
      multidiscipline clinical assessment is necessary during whole life.

PMID- 11320737
TI  - [Scoring systems for evaluating injury severity].
AB  - INTRODUCTION: Various trauma scoring systems were developed in order to assess
      injury severity and aid in decision making regarding further therapy and probable
      outcome. ANATOMIC INJURY SEVERITY SCALES: AIS--Abbreviated Injury Scale is a
      summary of all the values (from 1-9) for each organ or body part that is injured.
      ISS--Injury Severity Scale scores three dominant injuries from AIS scale. The
      maximum score for ISS is 75. MISS--Modified Injury Severity Score is a square of
      the AIS value for the three body parts with most severe injuries. PHYSIOLOGIC
      INJURY SEVERITY SCALES: GCS--Glasgow Coma Score is a numerical scale that
      assesses the severity of CNS injuries, that is the most appropriate system for
      numerical assessment of consciousness disturbance. Trauma score is a sum of GCS
      decreased for 1/3, plus the assessment of cardiopulmonary function. COMBINED
      ANATOMIC-PHYSIOLOGIC SCORING SYSTEMS: TRISS score (TS-ISS--trauma and injury
      severity score) TRISS combines ISS, TS, age of the patient and mechanism of
      injury, in order to determine survival probability. PTS--Pediatric Trauma Score
      takes into consideration all of the peculiarities of pediatric patients in
      response to trauma. Score values are from -6 to +12. APACHE--Acute Physiology And
      Chronic Health Evaluation Although it is complicated for general use, it still
      represents the most commonly used scoring system in Intensive Care Units. NEW
      SCORING SYSTEMS: MPM--Mortality Probability Models. MODS--Multiple Organ
      Dysfunction Syndrome. LODS--Logistic Organ Dysfunction Syndrome. SAPS--Simplified
      Acute Physiologic Score.

PMID- 11320738
TI  - [Dr. Koloman (Kalman) Kalivoda, a physician from Senta and a participant in the
      first congress of Serbian physicians and naturalists in 1904].
AB  - INTRODUCTION: The first congress of Serbian physicians and naturalists was held
      in Belgrade from September 5-7, 1904. There were 433 active registered
      participants listed in the Collection of Congress Papers. A great number of
      physicians from Vojvodina took part in the work of Congress. There is an
      authentic list of 27 physicians participants from Vojvodina. Although they made
      only 6% of all participants, their attendance was of utmost importance due to
      delicate political situation of that time. However, there is no explanation why
      only one physician from Vojvodina read his paper at this meeting. It was Dr.
      Koloman Kalivoda from Senta and his paper was tittled "Alcoholism and People".
      CONGRESS REPORT: Dr. Koloman (Kalman) Kalivoda was probably born between 1870 and
      1875. He moved to Senta in 1901 and in September 1901 started working as a
      regional physician in the third area. From 1908 he was a member of the Medical
      Board in Senta. He worked in Senta till October 31, 1918 when he submitted
      resignation from the post of a regional physician at the Assembly meeting. Then
      he moved from Senta and started civil service as a Hungarean Royal Resort
      physician. This paper presents Dr. Koloman's paper in complete, published in the
      Collection of Congress Papers. This paper received great attention and praises
      were found at several places such as: journal of "Czech Physicians", number 44
      from 1904; "Serbian Literary Herald", volume XIII, number 3 and in journal called
      "Pozor" from Moravska, number 146 from 1904. Further on, authors comment on Dr.
      Koloman's attitudes to alcoholism and treatment of alcoholics. Some were
      estimated as drastic: "the role of alcohol in rase cleansing"; how to
      "exterminate" alcoholics; suggestions for "interning drunkards overcome by fury"
      and suggestions for passing a law which would forbid drunkards to get married.
      Such attitudes of Dr. Koloman Kalivoda towards alcoholism may be associated with
      the circumstances of that time in Senta, because there are reliable data
      according to which in 1894 there were 26,648 inhabitants in Senta, whereas one
      brandy taproom or tavern came on every 213 inhabitants. Contrary to these
      attitudes, authors think that Dr. Koloman had very progressive ideas in regard to
      prevention of alcoholism as well as some suggestions and measures that should be
      undertaken by the society from the aspect of public hygiene.

PMID- 11320739
TI  - Viruses today and tomorrow.
AB  - The current studies show that viral infections can cause not only acute, but also
      persistent viral diseases. A certain number of viruses are able to incorporate
      their nucleic acid into the genome of the host-cell, leading to rearrangement of
      the cell genes and formation of malignant tumors. Viral persistence can cause
      manifestations of latent or chronic infections, as well as prion-caused slow
      infections of the central nervous system. Defective Di particles play an
      important role in maintaining viral persistence. Viruses are important agents
      involved in various disorders of the immunological homeostasis of the organism.

PMID- 11320740
TI  - [Evaluation of the level of hearing loss based on the results of tympanometry in
      children under 5 years of age with eustachian tube dysfunction].
AB  - INTRODUCTION: The paper describes the correlation between pathological
      tympanogram findings, and the degree and type of hearing loss. We have
      established a possibility of indirect evaluation of hearing loss based on
      tympanometric curve, in children aged five or less, with tympanometry established
      dysfunction of Eustachian tube. Statistical methods provided a degree of
      certainty based on which conclusions can be made on the degree of hearing loss.
      MATERIAL AND METHODS: The research was done from 1986 to 1998 in an insulated
      chamber of the audiological laboratory of the General Hospital in Subotica. 100
      children were tested, aged between 5 and 19. RESULTS: We have found that: type B
      tympanogram shows a statistically significant incidence in the examined group;
      patients with Eustachian tube dysfunction show a statistically significantly
      higher incidence of pathologic compared to normal audiogram, conductive hearing
      loss compared to other types of hearing loss, mild hearing loss compared to other
      types of hearing loss, horizontal audiogram form; based on performed tests, with
      a 95% expectancy, it can be concluded that 90% of patients whose Eustachian tube
      dysfunction is characterized by type B tympanogram simultaneously show (mild or
      medium) hearing loss, i.e. 70% of patients with type B tympanogram show a mild
      hearing loss, and 20% have a medium hearing loss. CONCLUSION: It is well known
      that the degree of hearing loss does not depend on tympanogram, but the above the
      research and statistical methods used indirectly lead to a conclusion that in
      mild dysfunction of Eustachian tube characterized by type C tympanogram the
      conductive hearing reduction does not exceed 25 dB, while in cases with type B
      tympanogram we can expect a conductive hearing loss between 20 and 40 dB, and in
      20% of cases a conductive hearing loss of 40-60 dB. The results of this research
      show that findings of tympanometric testing can be used as a basis for hearing
      evaluation in children below 5 years of age with a diagnosed Eustachian tube
      dysfunction.

PMID- 11320741
TI  - [Analysis of the plasmid profile of various Salmonella serotypes].
AB  - INTRODUCTION: Every year foodborne infections cause millions of illnesses but
      many of them go undiagnosed and unreported. The epidemiology of these illnesses
      is changing, new pathogens have emerged (Escherichia coli O157:H7, Cyclospora
      cayetanensis, Vibrio vulnificus). Salmonella spp. is the most common bacterial
      cause of acute enterocolitis with us. All over the world, as well as in our
      country the most often isolated serotype is Salmonella Enteritidis. A great
      problem in many countries is the multiresistant Salmonella Typhimurium, as well
      as other serotypes resistant to a great number of antimicrobial drugs (S. Hadar,
      S. Typhi). Clinical microbiologists are often asked to determine the relatedness
      of bacterial isolates. Recently, traditional methods of strain typing such as
      bacteriophage typing, resistotyping and serotyping, have been supplemented or
      replaced in many laboratories with newer molecular methods such as plasmid
      fingerprinting, ribotyping. PCR-based methods, etc. The goal of strain typing is
      to provide evidence that epidemiologically related isolates collected during an
      outbreak are also genetically related and thus represent the same strain.
      MATERIAL AND METHODS: In the laboratory for Enterobacteriaceae of the Institute
      of Public Health Novi Sad in the four year period (1995-1998) 3659 primary
      isolates of Salmonella spp. were isolated using standard bacteriological methods
      (cultural, biochemical and serological examination). For certain strain of
      Salmonella Enteritidis, S. Typhimurium and S. Hadar susceptibility to
      antimicrobial agents was tested by disc-diffusion test (Kirby-Bauer) and plasmid
      profiles were analyzed. Plasmid DNA was extracted by Birnboim and Doly alkaline
      lysis method and plasmid bands were separated by electrophoresis in agarose gel.
      RESULTS: In the period of 1995-1998 the most common serotype isolated was
      Salmonella Enteritidis with 3017 (82.5%) of the total number of isolated
      Salmonellas; S. Typhimurium 203 (5.5%), S. Hadar 118 (3.2%). Plasmid profiles
      were tested in 10 S. Enteritidis isolates that originated from patients with
      sporadic cases of diarrhea. All investigated strains had one plasmid band with
      molecular weight of 38 MDa. All isolates were susceptible to all antibiotics
      tested. Ten isolates of S. Hadar originated from one outbreak from food samples
      and stools of patients with diarrheal disease and from the worker in the
      restaurant. All isolates were resistant to ampicillin and streptomycin, and
      plasmid profile analysis showed 5 plasmid bands with molecular weights of 13,
      5.4, 4.2, 2.0 and 1.7 MDa. Chosen strains of S. Typhimurim were not epidemically
      related. Strains number 1, 3, 4, 5 were susceptible to all antibiotics tested,
      and had only one plasmid of 50 MDa, strain number 7 was resistant to streptomycin
      and had 2 plasmid bands of 50 and 1.7 MDa, other strains were multiresistant and
      had different plasmid profiles with 4-7 plasmid bands with molecular weights
      ranging from 50-1.4 MDa. CONCLUSION: Plasmid profile analysis is not a sufficient
      method for examination of Salmonella Enteritidis which is the most common cause
      of enterocolitis with us. It is, however, a helpful method for proving
      epidemiological and clonal relatedness of Salmonella isolates that are resistant
      to antimicrobial agents and have a great number of plasmids (such as some strains
      of S. Typhimurim and S. Hadar).

PMID- 11320742
TI  - Transvaginal ultrasonography of uterine cervix in prediction of the outcome of
      labour induction.
AB  - The aim of this prospective, blind, observational study was to estimate the role
      of transvaginal ultrasound examination of the uterine cervix in prediction of
      labour induction outcome in order to adequately chose patients that will have
      high chance for labour induction. One hundred patients scheduled for induction of
      labour had a transvaginal ultrasound scan during which cervical length and
      anterior cervical angle were assessed and the presence/absence of cervical
      tunneling was noted. Induction was successful if a vaginal delivery within 24
      hours took place. The difference between the mean values of the cervical lengths
      assessed by transvaginal ultrasonography in the group of successful (25.89 mm--SD
      8.27, 95% CI 23.65-28.13) and unsuccessful inductions (32.03 mm--SD 6.25, 95% CI
      29.01-34.96) is statistically significant (p < 0.05). The anterior cervical angle
      is not a useful predictor of induction success (sensitivity 22%, positive
      predictive value 40%). Cervical length assessed by transvaginal ultrasonography
      is a reliable predictor of labour induction outcome and the best statistical
      performance of this parameter this test has at the cut-off value of 30 mm
      (positive predictive value 87.2%, sensitivity 74%, specificity 70%).

PMID- 11320743
TI  - [Microcirculatory changes in chronic venous insufficiency].
AB  - INTRODUCTION: The venous system of lower leg can be topographically divided into
      two subsystems: superficial (extrafascial) and profound (subfascial).
      Functionally, we can divide circulation in to macrocirculation (arteries and
      veins) and microcirculation (arterioles, capillaries, and venules). Blood flow
      towards heart can be disturbed by different pathological conditions, and than
      chronic venous insufficiency (CVI) develops. First alterations occurs in
      macrocirculation, and after some period changes in microcirculation also appear.
      Those changes are leading to the ultimate stage in CVI--venous ulcer. RESULTS AND
      DISCUSSION: Previous conceptions that alterations in microcirculation in CVI are
      consequences of venous stasis, high pressure in capillaries and anoxic tissue are
      still actual. Observations that partial pressure of oxygen is higher in venous
      blood of lower limbs with ulceration than in limbs without ulceration lead to
      hypothesis that blood is passing directly from arterioles to venules over arterio
      venous temperature-regulating shunts in dermis. Histological and electron
      microscopic examinations certain alterations in the structure of capillaries.
      Raised pressure in these altered capillaries leads to exudation of plasma and
      fibrinogen in the interstitial space. Soluble fibrinogen is transformed to
      insoluble fibrin and forms fibrin cuffs. These cuffs are a barrier for normal
      diffusion of oxygen. Recently, it was observed that blood cells can adhere to the
      endothelial cells--Leukocyte trapping hypothesis. It can be explained by slower
      blood flow velocity and also by expression of certain endothelial and leukocyte
      adhesion molecules intercellular adhesion molecule-1 (ICAM-1), vascular cell
      adhesion molecule-1 (VCAM-1). This causes congestion of white blood cells which
      leads to tissue damage due to secretion of inflammatory mediators.

PMID- 11320744
TI  - [Current diagnostic methods of the specific distribution of adipose tissue].
AB  - INTRODUCTION: The classification of obesity into male or the android type and
      female or the gynoid type dates from the first clinical observations of J. Vague
      in the distant 1947. Researches carried out in the recent years show that in the
      android type of obesity there is an insulin resistance and hyperinsulinism as a
      metabolic bases for accelerated atherosclerosis. These insights imposed a need to
      determine body composition, and within it also the mass and the fat tissue
      distribution. The simplest anthropometric parameter which gives us insight into
      the nutritional status is BMI, while waist/hip ratio (WHR) offers orientation for
      the fat tissue distribution. MATERIAL AND METHODS: The subcutaneous fat tissue is
      measured by standard calipers. A particularly important anthropometric parameter
      which has been increasingly applied in the recent years is the sagittal abdominal
      diameter (SAD) measured by a simple caliper constructed by Kahn. This
      anthropometric indicator measures only the visceral fat tissue. As for other
      techniques, in the first place one should mention measuring of body density which
      presents a relation between the body mass an volume. Tetrapolar bioelectric
      impedance analysis is based on measuring the resistance of the body exposed to
      the impact of alternating current of 50 kHz and the strength of 800 microA.
      Double photon absorptiometry and X ray absorptiometry are precise methods for the
      determination of body composition, but they require expensive equipment and X ray
      absorptiometry also exposes the organism to certain radiation. Radio-isotopic
      techniques are based on measuring the total body liquid by marked deuterium or
      tritium and measuring of the total body potassium. Infrared spectrometry is a
      simple and not a particularly reliable method based on application of two sources
      of monochromatic light. Ultrasonographic measuring of fat tissue is a very
      favoured technique by which one can measure both the subcutaneous and visceral
      fat tissue. Measuring is carried out by transducer of 7.5 mHz for the
      subcutaneous and 3.5 mHz for visceral fat tissue. It is certain that fat-tissue
      depots can be most exactly measured by computerized tomography and nuclear
      magnetic resonance which, however, require a very expensive equipment.
      CONCLUSION: Modern concept of obesity implies an obligatory determination not
      only of the degree, but, which is even more important, of the type of obesity.
      Within these activities, besides the techniques already used so far (BMI, WHR),
      it is recommended to introduce measuring of the visceral fat tissue by SAD and
      ultrasonographic measuring of both fat-tissue depots into the everyday routine
      work.

PMID- 11320745
TI  - [Anti-U1RNP antibodies and lupus nephritis].
AB  - INTRODUCTION: Systemic Lupus Erythematosus is characterized by production of
      numerous autoantibodies as an abnormal immune response. The most important
      antibodies are those aimed at constitutive elements of cell nucleus. METHODS:
      After antigen typing of antinuclear antibodies in 30 patients with Systemic Lupus
      Erythematosus we analyzed the correlation between anti-Sm antibodies and anti
      U1RNP antibodies and the degree of disease activity, such as correlation of these
      two antibodies with some clinical manifestations of this disease. This study
      included patients who fulfilled all revised American Rheumatism Association
      criteria to diagnose systemic lupus. To determine the degree of disease activity
      we used Systemic Lupus Erythematosus Disease Activity Index after Bombardier. To
      detect antinuclear antibodies technique of indirect immunofluorescence and ELISA
      procedure for antigen typing of these antibodies were used. RESULTS: We
      registered antinuclear antibodies (ANA) in 100% of our patients, with domination
      of homogenous pattern of immunofluorescence (70%). Speakled pattern was
      registered in 16.66% and margin type in 6.66%. Using ELISA procedure of antigen
      typing of ANA we registered anti-U1RNP antibodies in 26.7% patients, while anti
      Sm antibodies were registered in 20%. CONCLUSION: Anti-U1RNP antibodies finding
      is associated with mild forms of disease and rare appearance of lupus nephritis,
      while anti-Sm antibodies finding is characteristic for very active forms of
      disease and often lupus nephritis.

PMID- 11320746
TI  - [Sex knowledge and behavior in male high school students].
AB  - INTRODUCTION: Adolescent sexual activity has increased in the last 30 years.
      Nowadays approximately 73% of male adolescent had sexual intercourse by the age
      of 18. Practice is not always followed by adequate knowledge and behavior.
      Therefore, it is of utmost importance to have appropriate education on sexual
      life and contraception in order to prevent unwanted pregnancies, abortions and
      spreading of sexually transmitted diseases. MATERIAL AND METHODS: Sexual behavior
      and knowledge was surveyed in a high school in Novi Sad among 520 male students,
      aged 15-19, in order to prepare lectures on sexual topics. RESULTS: Most
      information male teenagers got from different forms of mass-media (63.65%) and
      through communication with friends (50.58%). The communication with parents (5%)
      and experts (1%) is poor. According to their opinion, 69% have enough knowledge
      about sexuality and 62% about contraception, but 75.77% want further education
      from experts. 90% participated in some kind of sexual activity by the age of 18,
      and 84.3% had sexual intercourse for the first time at the age of 15.55 years, on
      average. artificial abortion occurred only in one case of pregnancy. Almost all
      young men knew about AIDS. The most common known means of contraception was
      condom (90%) and 70% consider it as the best method. 90% of male students
      consider abortion harmful, because it can cause infertility (51.38%). DISCUSSION:
      Most knowledge on sex life and contraception male adolescents gain from
      magazines, TV and friends, which can not be accepted as appropriate and
      undoubtedly can be incorrect and inadequate. Communication with parents and
      teachers is poor. Male adolescents are aware of their need for more education on
      these subjects and they want it from experts. CONCLUSION: Young men are not
      educated about sexual life and contraception well enough. Proper sexual education
      among adolescents is of great importance for psychic and reproductive health of
      young people.

PMID- 11320747
TI  - [Effect of alcohol consumption on recurrence of venereal diseases].
AB  - INTRODUCTION: Sexually transmitted diseases (STDs) comprise a large group of
      infections caused by different microorganisms including spirochetes, bacteria,
      chlamydia, mycoplasma, protozoa, fungi, parasites, and viruses. A considerable
      number of patients with sexually transmitted diseases are STD recurrences. As
      reported by Marijanovic and Lalosevic, in Belgrade, among patients who visited
      the City Department of Skin and Venereal Diseases, during 1985 and 1986 because
      of syphilis or gonorrhea, 22.8% had these diseases two or more times during their
      lives (male/female ratio 10:1). The aim of this study was to test the hypothesis
      that there is a relationship between alcohol use and recurrence of STD. MATERIAL
      AND METHODS: A case-control study was performed in Belgrade population, from
      June, 1997 to April, 1998. Participants were recruited among patients attending
      the City Department of Skin and venereal Diseases of Belgrade because of sexually
      transmitted diseases (syphilis, gonorrhea, nongonoccocal urethritis and genital
      warts). The case group comprised 101 patients who already had STD two or more
      times in their personal histories. The control group consisted of 210 patients
      treated at the same institution for micotic diseases, patients who either never
      had STD or had it only once (13% of controls) in their personal histories. All
      participants were men aged 20 to 50 years and all were from Belgrade. Data on
      demographic characteristics, sexual history and sexual behavior, and data on
      antisocial behavior were collected from all participants using an anonymous
      questionnaire. In the present paper only data on alcohol use are presented. In
      the analysis of data chi 2-test was used. RESULTS: STD recurrence patients in
      comparison to their controls used alcohol more frequently (56.3%:16.1%),
      especially hard liquors, and 55.5% of them used alcohol at the time of STD
      infection. DISCUSSION: In the present study STD recurrence patients consumed
      alcohol more frequently than their controls, especially hard liquors. In the
      study of Myliueva et al, 50% of venereal disease patients consumed alcohol now
      and then and 10% consumed alcohol frequently. Scheidt and Windle found that 60%
      of alcoholics had at least one sexually transmitted disease as the result of a
      high number of sexual partners, low use of condoms and practicing sex for drugs
      or money. Alcohol has a depressive effect on central nervous system, reduces
      anxiety and increases libido. CONCLUSION: The obtained results support the
      hypothesis that alcohol use is related to recurrence of STDs.

PMID- 11320748
TI  - [Evaluation of the quality control system in blood transfusion service].
AB  - INTRODUCTION: Implementation of quality system improvement at the Blood
      Transfusion Institute Novi Sad, included adjustments in practice to the request
      of ISO 9001 standard. Quality improvement must be a permanent activity of the
      Institute. The audit is a management tool for monitoring the quality assurance
      system and is either a quality audit or a medical audit. A well planned,
      comprehensive quality audit covers each activity of the Blood Transfusion
      Institute. The procedures may be internal or external. INTERNAL AUDIT: Quality
      manager is responsible for annual internal quality audits. The purpose of
      internal audits is to check the efficiency of the quality system in terms of
      realization of quality policy, fulfullment of designed targets and implementation
      of quality system documents. An internal quality audit is performed in accordance
      with the procedure and audit findings are reported to the management in a form of
      internal quality report as a part of quality system review. The findings must be
      communicated to all persons responsible for the controlled area. Quality manager
      can initiate an internal quality audit whenever it is realized that problems
      about the quality system have occurred. Audits are conducted by the quality
      manager or an audit team. The accurate list of internal auditors is kept in the
      Institute archive. MEDICAL AUDIT: Medical audit carried out by a transfusion
      committee, evaluates the quality of blood transfusion for determining the degree
      of compliance with established local or national guidelines, in order to promote
      optimal transfusion practice. CONCLUSION: Audits are not only used for
      determining further quality management activities, but also make basis for
      creating and maintenance of excellent relations with product and service users.
      Considering all this, Blood Transfusion Institute exceeds the requirements of ISO
      9000 standards series.

PMID- 11320749
TI  - [Radical vulvectomy with inguino-femoral lymphadenectomy in the surgical
      treatment of vulvar carcinoma].
AB  - INTRODUCTION: Vulvar carcinomas comprise almost 5% of all malignant tumors of the
      female genital tract. The final diagnosis is made after histologic examination of
      biopsy specimens obtained from different sites in the vulva. Primary therapeutic
      approach in all cases is surgery, whereas the operative procedure depends on the
      size and location of the lesion, stage of the disease, general condition and age
      of the patient, as well as on the condition of the surrounding tissue and
      possible continuance of sexual life. METHODS: In the period from 1985-1999, there
      were 39 patients with invasive forms of vulvar carcinomas operated at the
      Department of Gynaecology in Novi Sad. Radical vulvectomy associated with
      inguinal-femoral lymphadenectomy was performed in 26 (66.6%) patients. During
      1994, a wide "butterfly-shaped "block" dissection of the vulva, pubis and
      inguinal area was done, whereas during the following period, the operative area
      was reduced by application of separate inguinal incisions after Hacker, leaving
      the tissue bridge in between. RESULTS: The mean age of operated patients was 62.1
      years (34-85). There were 53.8% stage I, 17.9% stage II, 20.7% stage III and 7.6%
      stage IV patients. In patients undergoing radical surgery the average number of
      extirpated lymph nodes was 16.3 out of which in 7 (26.9%) cases the nodes were
      positive. Lethal outcome was recorded in 4 (15.3%) patients. Two (7.6%) died of
      pulmonary thromboembolism and 2 (7.6%) during the following 5 years for diffuse
      dissemination of metastases. During 1994, complications were recorded in 69.2%
      operated patients versus 7.6% recorded during the following period. CONCLUSIONS:
      Radical vulvectomy associated with bilateral inguinal-femoral lymphadenectomy is
      a standard procedure in surgical treatment of invasive stages of vulvar carcinoma
      protruding more than 1 mm. The application of two separate inguinal incisions
      after Hacker resulted in shortening the intrahospital postoperative period from
      34.2 to 14 days and reduction of the rate of wound dehiscence and postoperative
      complications in the period following 1994.

PMID- 11320750
TI  - [Congenital postero-lateral right diaphragmatic hernia--case report].
AB  - OBJECTIVE: There are three types of congenital diaphragmatic hernias (DH):
      posterolateral (Bochdalek) diaphragmatic hernia, subcostosternal (Morgagni's)
      hernia and esophageal hiatal hernia. The posterolateral (Bochdalek) diaphragmatic
      hernia is the result of a congenital diaphragmatic defect in the posterior costal
      part of the diaphragm in the region of 10th and 11th ribs, which allows free
      communication between the thoracic and abdominal cavity. The defect is usually
      found at the left side (90%) but may occur on the right side, where the liver
      often prevents detection. CASE REPORT: We present a 9-year-old girl with
      persistent cough during four weeks, vomiting and loss of appetite. She was
      admitted in hospital after one month ambulatory treatment without success. Chest
      x-ray showed an infiltrative shadow in basal lobe of the right lung and multiple
      radiolucencies over the right hemithorax. Irrigography confirmed presence of
      contrast in the right hemithorax (with herniation of colon in the right lung).
      The child had a restrictive type of pulmonary function and was operated after
      establishing the diagnosis of the disease. Posterolateral diaphragmatic defect
      was established intraoperatively with diameter 10 x 11 cm and with ascending
      colon prolapse, caecum appendix and part of colon transfersum. The child was in
      good condition after operation. Control X-ray was normal and the child has a
      normal pulmonary function on routine controls. COMMENT: The posterolateral right
      congenital DH is a rare diaphragmatic defect. The symptoms are noncharacteristic
      and patients with this disease can be without symptoms for a long period. The
      main tool for diagnosis of congenital DH is radiography, whereas treatment is
      surgical.

PMID- 11320751
TI  - [The premature infant as an anesthesiology problem--case report].
AB  - INTRODUCTION: In pediatric anesthesia, neonatal anesthesia takes a special place
      because of its specific problems connected to physiological properties of
      newborns and their adaptation after birth. Adaptation itself, represents a line
      of changes in organ function and organ systems for new circumstances of life.
      DISCUSSION: Preoperative evaluation means identification of any present disease
      that might need preoperative treatment or specific course of anesthesia and
      surgery, in order to determine the most proper anesthesia regimen for the child.
      The primary aim of anesthesia is analgesia, unconsciousness and muscle
      relaxation, keeping vital parameters in optimal state. CONCLUSION: Newborns and
      infants, as specific age groups, demand special preoperative evaluation and
      approach to surgery. Knowledge of newborn's physiology and pathology either
      congenital or acquired is necessary for optimal choice of anesthesia regimen and
      surgical procedure in order to minimise postoperative complications.

PMID- 11320752
TI  - [Surgeons, midwives and physicians in Senta in the 18th and 19th centuries].
AB  - INTRODUCTION: Authors present history data on development of the medical
      profession in Prussia, Germany, Austria and Hungary, that is countries from which
      surgeons, midwives and physicians most often came to work in Senta. It has been
      established that mostly junior physicians and "surgeons" came to our country, and
      from the forties till nineties of the 19th century they made a considerable
      number of our first medical professionals. In 1872 a law was passed according to
      which only doctors of medicine with university degrees were allowed to practice
      medicine, and so junior physicians gradually disappeared. OUR INVESTIGATIONS AND
      DATA: The earliest data on health care of Senta date back to the tax register for
      1771 according to which the expenditure for November contained expenses for bread
      and half of the allowance for fodder which were paid to the city surgeon.
      According to the census from 1774/75 the first registered barber surgeon was
      Mihalj Nad, whereas four years later he was advertised as a surgeon in the tax
      register. In the following years more surgeons were registered: Janos Grubanovic,
      Jozef Forgac, Antal Kovac and Johan Brun. The first city midwife registered in
      the city court record in 1794 was Doroteja Gubik. During 18th century at the
      territory of Senta only barbers and surgeons were known, and there were no
      graduated physicians. The first city physician who received a degree from the
      School of Medicine was Samuel Borod who started working in Senta on April 24,
      1822. After that, during 19th century the following physicians worked in Senta:
      Dr. Laslo Eres, Dr. Jozef Cendic, Dr. Simon Slezinger, Dr. Janos Nepomuki Revai,
      Dr. Zigmund Veksler, Dr. Adolf Glikstal, Dr. Jozef Kelner, Dr. Mor Lendvai, Dr.
      Sandor Meri, Dr. Jozef Havel and Dr. Jozef Rejcer. Dr. Janos Nepomuki Revai was
      at the head of the public health care of our town for 40 years, whereas his
      predecessor Dr. Jozef Cendic was engaged in this honorable profession for 30
      years. Dr. Janos Revai was an outstanding person who introduced vaccination
      against smallpox and diphtheria, prevented further spreading of trachoma, stopped
      a great epidemic of cholera in 1892/93 and continually worked on promotion and
      improvement of health care in Senta. During 19th century the following surgeons
      worked in Senta: Istvan Budai, Mihajlo Zivkovic, Jozua Veksler, Istvan Kalman,
      while the last surgeon working in Senta was Lajos Kuti. In the 19th century the
      following midwives were registered in Senta: Apolonija Hauser, Verona Kremzer,
      Regina Zinger, Jozefa Vig, Apolonija Bauc, Apolonija Hauber and Rozalija Huska.
      At the end, authors list all surgeons, midwives and physicians with complete data
      on them from all available documents.

PMID- 11320753
TI  - [Technetium-99m production for use in nuclear medicine].
AB  - INTRODUCTION: Technetium-99m is the most important radioisotope used in nuclear
      medicine. Its routine application is ensured by introduction of 99Mo/99mTc
      generators. This paper reviews the present status and perspectives of different
      types of generators. Novelties in the production of either 99Mo for generators or
      directly 99mTc by using accelerators are also included. PRODUCTION OF 99MO IN
      NUCLEAR REACTORS AND 99MO/99MTC TYPES OF GENERATORS: The main source of 99Mo is a
      nuclear reactor. Nuclear reaction 99Mo(n, gamma)99Mo is rather simple, but the
      main disadvantage is a low specific activity of 99Mo. For routine production the
      nuclear reaction 235U(n,f)99Mo is used. It gives high yields of 99Mo of very high
      specific activity. However, its main disadvantages are high costs and generation
      of large quantities of highly radioactive waste. Depending on the separation
      method several types of generators were developed. The predominant is the
      chromatographic generator based on fission-produced 99Mo. Due to the
      disadvantages of (n,f)99Mo production, the alternatives based on (n, gamma)99Mo
      were developed. However, sublimation (except low temperature sublimation) and
      extraction generators at the present stage have no perspective. Only gel
      generators are promising. PRODUCTION OF 99MO AND 99MTC IN ACCELERATORS: Several
      nuclear reactions are considered. 100Mo(gamma, n)99Mo gives 99Mo of low specific
      activity. So it could be used in production by sublimation generators. The
      reaction 100Mo(p,pn)99Mo was also investigated but it seems not to be suitable
      for routine production of 99Mo. 99mTc can be directly produced by 98Mo(p,
      gamma)99mTc and 100Mo(p,2n)99mTc nuclear reactions. It seems that the latter
      could serve as an auxilliary source of 99mTc. CONCLUSION: At present
      chromatographic generators based on fission-produced 99Mo seem to have no real
      alternative. Gel and in lesser extent sublimation generators are prosperous, but
      still not suitable for large scale production of 99mTc. The accelerators offer
      good possibilities but a real alternative to fission 99Mo has not been found yet.

PMID- 11320754
TI  - [Hypoglycemic effect of sodium salt of monoketocholic acid in diabetic rats].
AB  - INTRODUCTION: In recent years experiments have showed that synthetic derivatives
      of bile acid affect blood glucose level. The aim of this work was to study the
      influence of sodium salt of monoketcholanate (MKH) on blood glucose level in rats
      with induced diabetes. MATERIAL AND METHODS: Diabetes was induced with
      streptozotocin applied intraperitoneally in a dose of 70 mg/kg body weight. The
      experiments were carried out in white laboratory rats. They were divided in two
      groups: group A--rats with induced diabetes (n = 10) and group B--rats with
      normal blood glucose level (control group, n = 10). Both groups of animals were
      anesthetized with urethan applied intraperitoneally in a dose of 0.75 g/kg body
      weight and were divided in two subgroups. The subgroups, one of each group of
      animals, were treated intranasally with 2% solution of MHK, in dose of 0.2 ml/kg
      body weight. The other two subgroups (control subgroups) received saline solution
      intranasally in a dose of 0.2 ml/kg body weight. Blood was taken periodically
      from the tail vein and blood glucose level was determined at 0, 15, 30, 45, 60,
      90, 120 and 180-th minutes after treatment. RESULTS: In the group of rats with
      normal blood glucose level (group B) MKH did not show any statistically important
      changes in blood glucose level. In group of rats with induced diabetes (group A).
      MKH significantly decreased blood glucose level at 30, 45, 60 and 90-th minute in
      comparison to the diabetic rats treated with saline solution. CONCLUSION: The
      results of the study show that intranasally applied 2% solution of MKH has a
      hypoglycemic effect, but only in rats with diabetes. The same substance has no
      influence on blood glucose level in normoglycemic rats.

PMID- 11320755
TI  - Uses of epoetin for anemia in oncology.

PMID- 11320756
TI  - Emerging issues in measles.

PMID- 11320757
TI  - Ventilatory capacity indices in Malawian children.
AB  - OBJECTIVE: To compare ventilatory capacity indices in healthy Malawian school
      children with those of other ethnic Africans and Caucasians. DESIGN: Forced vital
      capacity (FVC), forced expiratory volume in one second (FEV1), peak expiratory
      flow rate (PEFR), FEV1 expressed as a percentage of FVC (FEV%), weight and
      height. SETTING: Two primary schools in urban Blantyre, Malawi. SUBJECTS: Five
      hundred and fourteen apparently healthy school children (230 boys and 284 girls)
      aged six to 17 years. RESULTS: Ventilatory capacity indices (FEV1, FVC and PEFR)
      strongly and significantly correlated to body size and age of children of both
      sexes. The mean value of FEV% was 88.3% and it did not change significantly with
      increasing body size and age of children. The mean values of FEV1 and FVC were
      9.8% and 10.8% higher in boys than in girls, respectively. The 1.4% gender
      difference in PEFR values was statistically non-significant. For FEV1 and FVC
      values, the average differences between Malawian and European children were
      between 20.5% and 23% while for PEFR the ethnic difference was about 12%. The
      Malawian children have similar ventilatory capacity indices to those of Nigerian,
      Jamaican and Tanzanian children. CONCLUSION: Prediction equations calculated in
      this study should be used for interpretation of ventilatory capacity indices in
      Malawian children instead of reference values for Caucasians or ethnic scaling
      factors. Computation of regional reference values for ventilatory capacity
      indices shall be continued. It shall embrace additional factors contributing to
      variance in respiratory functions such as customary physical activity, local
      environmental conditions, altitude of residence, nutritional status and smoking.

PMID- 11320758
TI  - Paediatric intussusception in Calabar, Nigeria.
AB  - OBJECTIVES: To determine prevalence, clinical presentation, evaluate management
      methods and outcome of paediatric intussusception in Calabar. DESIGN: A
      retrospective study. SETTING: University of Calabar Teaching Hospital, Calabar,
      Nigeria. PARTICIPANTS: All cases of intussusception in children that presented at
      the children emergency Room and Surgical Outpatient Department of the University
      of Calabar Teaching Hospital between 1989 and December 1998. RESULTS: The mean
      age was 7.5 months with a male:female ratio of 1.8:1. The main presenting
      symptoms were vomiting in 76 (85.3%) patients, general irritability in 69 (77.5%)
      patients, bleeding per rectum in 47 (52.8%) patients and palpable abdominal mass
      in 38 cases (42.6%). Majority of the patients presented late to hospital beyond
      36 hours since onset of illness and had had enema administration before
      presentation, a popular phenomenon in the region. Diagnosis of this condition was
      confirmed clinically in fifty nine patients (66%). Eighty one patients (91%) had
      laparotomy, the only method of treatment available with simple manual reduction
      while in eight patients (9%) laparotomy was accompanied with resection and
      anastomosis for bowel with doubtful viability. CONCLUSION: Time lapse from onset
      to presentation is not a criterion for choosing between operative and non
      operative reduction. The clinical status and abdominal evaluation of the patients
      are the important features to consider. Operative reduction in most instances
      involve manual reduction hence should be preceded by conservative methods of
      reduction.

PMID- 11320759
TI  - Left-handedness as a risk factor for head injuries.
AB  - OBJECTIVE: To study prevalence of left-handedness among traumatic patients with
      head injuries. DESIGN: A case-control study. SETTING: Queen Elizabeth Central
      Hospital, Blantyre, Malawi. SUBJECTS: One hundred and sixty three traumatic
      patients newly admitted to a surgical ward at Queen Elizabeth Central Hospital,
      Blantyre during one month period with exception of patients with arm injury,
      severe injury and confused patients. MAIN OUTCOME MEASURES: Maximal grip strength
      of both hands, questionnaire on hand preferred for eight habitual activities.
      RESULTS: The overall prevalence of left-handers determined on the basis of
      bilateral asymmetry in maximal grip strength was non-significantly higher in
      traumatic than in the control group. Relative to the control group, lefties were
      over-represented among victims of head injury, while prevalence of left-handers
      among patients with leg and trunk injuries and among controls was similar. Left
      handed patients were more likely to sustain head traumas during fighting, road
      transport accidents and sport activities. Possible reasons for increased level of
      traumatisation among sinistrals are discussed. CONCLUSION: Left-handedness is a
      risk factor for head injuries obtained during confrontational activities.
      Therefore, left handers should avoid such type of behaviour in order to reduce
      traumatisation rate.

PMID- 11320760
TI  - Illegal abortions in Addis Ababa, Ethiopia.
AB  - OBJECTIVES: To identify the primary abortionist while the patient is in the
      hospital; to determine the type of materials used to terminate the pregnancy; to
      determine the number of attempts made to terminate the index pregnancy and; to
      characterise women with induced abortions at five hospitals in the City of Addis
      Ababa. DESIGN: Cross-sectional hospital-based descriptive multi-centre (WHO)
      study. SETTING: Addis Ababa University, Faculty of Medicine. SUBJECTS: All cases
      of abortions admitted to the study hospitals at five hospitals with obstetric and
      gynaecologic services. MAIN OUTCOME MEASURES: Identification of the primary
      abortionist, the places where abortion is carried out, the number of attempts
      made to terminate the index pregnancy and the materials used to terminate the
      pregnancy and reasons for terminating the pregnancy. RESULTS: A total of 2275
      cases of abortion had been identified and managed in the five study hospitals.
      The study demonstrated that 984 (43.3%) were spontaneous abortions. Of the 1290
      illicit or unsafe abortions admitted by the patients (certainly induced) in 455
      (35.3%) of the abortions were performed by the health assistants, 366 (28.3%)
      self-induced, and 306 (23.7%) by cleaners working in the operation theatres. In
      744 (60%) of the abortion procedures were carried out at the abortionists home
      while 452 (35%) at the patients' home. The remaining 94 (5%) of the abortions
      were done safely in the hospital or doctor's office by professionals. The most
      commonly used methods for inducing the abortions were; in 417 (32.3%) high doses
      of ampicillin per OS, and in 414 (32.1%) by inserting plastic tubes (intravenous
      giving set) per vagina. CONCLUSION: The issue of abortion clearly presents an
      enormous complex moral and ethical dilemma. The study results are very clear.
      Where abortion is illegal or where the services are not readily available and/or
      personnel are not well trained, unsafe abortion carries a high risk of
      complications, permanent damage resulting in infertility and even death. The
      question is not really whether or not abortion should be legal or illegal but
      whether or not it should be prevented through modern family planning methods,
      safe or unsafe abortions. In all societies no matter what the legal moral or
      cultural status of abortion are, there will be some women who will desperately
      seek to terminate an unwanted or unplanned pregnancy. Unsafe abortion is a major
      medical and public health problem in Ethiopia. The magnitude of the problem in
      terms of numbers affected, and severe adverse consequences can no longer be
      ignored.

PMID- 11320761
TI  - Re: Identification of acid fast bacilli in histologically diagnosed tuberculous
      lymphadenitis.

PMID- 11320762
TI  - General practitioners and clinical guidelines.
AB  - OBJECTIVE: To assess the attitudes of general practitioners in Harare, Zimbabwe,
      towards the use of clinical practice guidelines (CPG's). DESIGN: Cross sectional
      survey. SETTING: General practitioners in private practice within the urban
      Harare (Zimbabwe) environs. SUBJECTS: Two hundred and thirty two general
      practitioners in Harare, Zimbabwe. MAIN OUTCOME MEASURES: The response to a
      questionnaire enlisting attitudes to CPGs. RESULTS: Questionnaires were sent to
      232 general practitioners. Of these, 137 (59.1%) returned a completed
      questionnaire. Among the respondents, 95.6% felt that general practitioners
      should be involved in the development of guidelines, 72.6% had read at least one
      guideline, 65.9% were prepared to use guidelines in their practice, 61.6% thought
      that guidelines would improve their treatment ability, and 59.7% thought that
      guidelines would improve their knowledge of disease. 76.5% felt that the
      government should not legislate, 66.2% felt that guidelines reduce practitioners'
      flexibility and 57.9% felt that guidelines would not improve their diagnostic
      ability. CONCLUSION: The respondents were, in general, favourably disposed
      towards CPGs. Most had already read some guidelines, and about two thirds were
      prepared to use them. Almost all respondents felt that general practitioners
      should be involved in the development of guidelines for use in general practice.
      These general practitioners felt that guidelines were likely to help them treat
      patients than to make a diagnosis. Despite these favourable attitudes, many
      practitioners felt that guidelines would limit their personal flexibility in
      caring for patients. Organisations developing or implementing CPGs in general
      practice should address these concerns.

PMID- 11320763
TI  - Psychiatric aspects of criminal homicide in Nigeria.
AB  - OBJECTIVES: To investigate the Psychiatric aspects of homicide in Nigeria, and,
      the psychosocial and forensic background of homicide offenders in Nigeria; to
      determine the role of the mental health services in the disposal of the accused
      by the criminal justice system. DESIGN: Retrospective study, involving interview
      of homicide convicts and, the scrutiny of court and prison documents for relevant
      clinico-forensic data. SETTING: Federal Prison, Jos, Nigeria. RESULTS: One
      hundred and eighteen subjects participated in the study. Psychotic disorder
      (mainly paranoid schizophrenia) and alcohol intoxication accounted for the
      offenses of 28 (24%) accused. Amnesia for the events occurred in psychotic
      offenders. Psychiatric services were underutilised in the trial and disposal of
      the accused. Marked psychosocial maladjustment in offenders was suggested by a
      high rate (45%) of substance use disorders predating the homicide events. Thirty
      three (28%) offenders had dysfunctional family circumstances. Eighty six per cent
      of the accused were first time offenders. Adverse life events, predominantly in
      relation to the victims, were reported by 33 (28%) of the accused in the month
      predating the events. CONCLUSIONS: Psychiatric disorders and substance use are
      significantly involved in homicide events in Nigeria. There is a need for close
      liaison between the psychiatric and criminal justice systems, in the disposal of
      all homicide accused. A continuing study of homicide in Nigeria is recommended,
      to bridge the gap in our present level of knowledge.

PMID- 11320764
TI  - Measles sero-surveillance during mass immunisation campaign in Malawi.
AB  - OBJECTIVE: To determine age-specific measles antibody prevalence and serological
      response to vaccination during the first mass campaign against measles in Malawi.
      DESIGN: Cross-sectional study using a questionnaire and a serological particle
      agglutination (PA) test. SETTING: Two health centres in Salima district, central
      Malawi during the national measles immunisation week, 1998. PARTICIPANTS: Two
      hundred forty six under-five year old children. RESULTS: Seventy four per cent of
      enrolled children (95% confidence interval, 69-80%) were measles PA antibody
      positive at the vaccination. The antibody positive rate was 17.4% in children
      aged 8-12 months and gradually increased up to 90% by four years-old, while the
      age-specific geometric mean titers (GMTs) in 48-59 months-old group were
      significantly lower than those in 24-35 months-old group, suggesting antibody
      waning after previous vaccination (p = 0.0047). Two hundred and thirty follow up
      specimens were obtained eight weeks after the vaccination. The sero-conversion
      rate was 100% in 58 children sero-negative at the vaccination and the GMTs in 172
      children seropositive at the vaccination were significantly increased (p <
      0.001). CONCLUSION: These results indicated that the first national measles
      immunisation campaign successfully immunised the enrolled children or gave a
      booster response of antibody levels. It was also confirmed that the PA test was
      easy to perform and most suitable for the field condition in developing
      countries.

PMID- 11320765
TI  - Foodborne diseases in Kenya.
AB  - OBJECTIVES: To determine the occurrence of foodborne disease outbreaks in Kenya
      and the efforts employed to combat them. DESIGN: Cross-sectional survey. SETTING:
      Forty two districts in Kenya between 1970 and 1993. STUDY SUBJECTS: Foodborne
      disease outbreak episodes due to Staphylococcus aureus, Clostridium perfringens,
      Clostridium botulinum, Bacillus cereus, Escherichia coli, Campylobacter jejuni,
      Yersinia enterocolitica, Listera monocytogenes, chemicals, aflatoxin, plant and
      animal poisons. OUTCOME MEASURES: Number and aetiological causes of foodborne
      disease outbreaks reported in the study period. RESULTS: Thirty seven food
      poisoning outbreaks were reported to the Ministry of Health from various parts of
      the country in the study period 1970 to 1993, and only 13 of these involving a
      total of 926 people were confirmed to be due to particular aetiological agents.
      Foods that were involved included milk and milk products, meat and meat products,
      maize flour, bread, scones and other wheat products, vegetables and lemon pie
      pudding. A high number of food poisoning cases were treated as outpatients in
      various health facilities. CONCLUSION: Under-reporting, inadequate investigation
      of outbreaks and inadequate diagnostic facilities suggest that foodborne disease
      outbreaks are more than is recorded by the Ministry of Health.

PMID- 11320766
TI  - Compliance with medication in patients with heart failure in Zimbabwe.
AB  - OBJECTIVES: To determine the extent of adherence to prescribed medication in
      patients with chronic heart failure and to determine to what extent patients
      recall information given regarding their medication. DESIGN: Compliance and
      knowledge of prescribed medication was studied in 22 heart failure patients [mean
      age 45 +/- 4 (range 40-67); 14 (64%) male], using in-depth interviews performed
      30 days after having been prescribed medication. All patients received
      standardised verbal and written information regarding their medication. SETTING:
      Patients attending four general practices in the private sector (in Harare,
      Zimbabwe) for at least six months prior to enrolling were in included in the
      study. RESULTS: Only 12 (55%) patients could correctly name what medication had
      been prescribed, 11 (50%) were unable to state the prescribed doses and 14 (64%)
      could not account for when the medication was to be taken, that is to say, at
      what time of day and when in relation to meals the medication was to be taken. In
      the overall assessment six (27%) patients were found non-compliant and 16 (73%)
      patients were considered as possibly being compliant with their prescribed
      medication. CONCLUSIONS: Non-compliance was common in heart failure patients, as
      were shortcomings in patients' knowledge regarding prescribed medication, despite
      efforts to give adequate information. There exists a need for alternative
      strategies to improve compliance in these patients.

PMID- 11320767
TI  - Schistomiasis of the spinal cord: report two cases.
AB  - Schistosomiasis affects over 200 million people worldwide. Schistosomiasis of the
      spinal cord is a rare occurrence. In Africa, there have been recent reports from
      Egypt and South Africa. In Uganda, the last histological records were over two
      decades ago. Schistosomiasis of the spinal cord is commonly caused by Schistosoma
      mansoni although Schistosoma haematobium has been isolated. Two case reports are
      presented. In both patients, the diagnosis was made retrospectively. The first
      patient was a female patient with a lesion in the thoracic region. The second
      patient was a 21 year old male with a lesion in the conus. Apart from a block on
      the myelograms, all other laboratory investigations were negative. The diagnosis
      was made histologically in both cases with the identification of eggs of
      schistosoma in the spinal cord. The eggs could however, not be retrieved from the
      stool or urine samples. Both patients were treated with antischistosomal drugs
      and steroids. On follow up they had marked improvement in their neurological
      signs. We hope to renew attention in this rare but devastating neurological
      manifestation of a disease which affects many in our region and which if left
      untreated can lead to permanent neurological damage.

PMID- 11320768
TI  - Infant feeding practices during the first six months of life in a rural area in
      Tanzania.
AB  - OBJECTIVE: To assess breastfeeding practices in infants aged 0-6 months,
      focussing particularly on beliefs, knowledge and practices affecting exclusive
      breastfeeding. DESIGN: A house-to-house survey with individual interviews using a
      structured questionnaire, key informants interviews and focus group discussions.
      PARTICIPANTS: One hundred and seven mothers were interviewed, nearly all of those
      living in Nkinga community with infants less than seven months old. The focus
      group discussions and key informant interviews were also held. SETTING: Nkinga
      community, Igunga District, Tabora region, Tanzania. RESULTS: Sixty four per cent
      of the sample was put to the breast within two to eleven hours. Prelacteal feeds
      were given to about 25% of the infants. The type of prelacteal fluid given was
      mainly glucose water in hospital and plain water with home deliveries. Forty six
      per cent of the mothers discarded colostrum. The median duration of exclusive
      breastfeeding was about two months and of full breastfeeding was about four
      months. CONCLUSION: The average duration of exclusive breastfeeding, though far
      below recommended levels, is higher than is found in most studies in Africa and
      Tanzania. This may be due to the efforts of hospital staff who had received
      special training on breastfeeding in recent years.

PMID- 11320769
TI  - Clinical and parasitological aspects of Bancroftian filariasis in Hale, northeast
      Tanzania.
AB  - OBJECTIVES: To document the endemicity characteristic of Bancroftian filariasis
      and to validate the effect of blood sampling time adjustment method on
      microfilarial intensity in relation to sex and age. DESIGN: Community based cross
      sectional survey. SETTING: Four rural communities in Hale area, Muheza district,
      northeast Tanzania. SUBJECTS: A sample of 1,025 inhabitants aged one year and
      above. MAIN OUTCOME MEASURES: Chronic clinical manifestations (elephantiasis and
      hydrocele), microfilarial prevalence as well as crude and time adjusted
      microfilarial geometric mean intensity (GMI). RESULTS: Clinically, 6.9% of
      examined individuals had elephantiasis and 28.5% males aged 15 years and above
      had hydrocele. Prevalence of Wuchereria bancrofti infection was 31.8%, with
      females and males showing a microfilarial rate of 32.1% and 31.5% respectively.
      Both the clinical manifestations and microfilarial prevalence increased with age.
      The GMI among microfilarial positive individuals for the crude microfilaraemia
      was 1,122 or 1,175 mf/ml of blood after adjustment of the sample to the expected
      level if it had been collected at peak hour. In different age and sex groups, the
      adjusted microfilarial GMI was slightly higher but exhibited a similar pattern to
      crude microfilaraemia count suggesting that time of blood sampling has similar
      effect on each age and sex group.

PMID- 11320770
TI  - Symptoms and findings related to HIV in women in rural Gutu District, Zimbabwe,
      1992 to 1993.
AB  - OBJECTIVE: To relate self-reported morbidity and clinical findings to HIV-status
      in rural women in Zimbabwe. DESIGN: A cross sectional study. SETTING: 12 randomly
      selected villages in rural Gutu District, Zimbabwe. SUBJECTS: In 1992 to 1993 all
      women of fertile age (15 to 44 years) in the selected villages were interviewed
      and examined (n = 1,213). Retrospectively, HIV status was assessed anonymously
      from frozen blood samples. MAIN OUTCOME MEASURES: Self-reported morbidity, body
      mass index (BMI), arm circumference, palpable lymphnodes, prevalence of syphilis,
      haemoglobin, HIV status. RESULTS: Overall HIV prevalence was 22%. Mean
      haemoglobin (Hb) was significantly lower (p < 0.005) and anaemia was
      significantly more common (p < 0.001) among HIV positive women. Syphilis
      prevalence was 2.2%, a positive syphilis test increased the risk of being HIV
      positive three-fold. Persistent cough was significantly more common in HIV
      positives (OR = 3.0, 95% CI 1.4-6.2). Palpable lymphnodes was the most common
      clinical finding and generalised lymph adenopathy had a positive predictive value
      of 67% for HIV. Self-reported morbidity was low and no increased pregnancy loss
      was reported related to HIV. CONCLUSION: The low morbidity found in 1992 to 1993,
      in spite of the high prevalence, indicates a fairly short duration of the HIV
      infection and would also have contributed to the late awareness of the problem.

PMID- 11320771
TI  - Storage of breast milk: effect of temperature and storage duration on microbial
      growth.
AB  - OBJECTIVE: To study the effect of storage duration at varying temperature ranges,
      the pattern of microbial isolates and the quantity of colony-forming units (CFU)
      on expressed breast milk. DESIGN: Cross sectional study. SETTING: Bacteriology
      laboratory, University of Zimbabwe in Parirenyatwa Hospital, Harare. MAIN OUTCOME
      MEASURES: The temperature, storage duration and types of micro-organisms in
      freshly expressed breast milk. RESULTS: Freshly expressed human breast milk
      contained microbial non-pathogens of skin flora. There was no growth of organisms
      in stored breast milk after four hours, eight hours, 24 hours and 72 hours
      storage duration at temperature ranges 0 to 4 degrees C (freezing temperature), 4
      to 10 degrees C (refrigerator temperature), 15 to 27 degrees C (room temperature)
      and 30 to 38 degrees C (high temperature) respectively. Growth was detected after
      the storage durations and organisms isolated were both pathogens and non
      pathogens with low counts. Average colony counts was (CFU < 200). CONCLUSION: The
      study revealed that storage duration for expressed breast milk should not exceed
      24 hours in refrigerator temperature (4 to 10 degrees C), eight hours at room
      temperature (15 to 27 degrees C) and four hours at high temperature (30 to 38
      degrees C). Although freezing temperature (0 to 4 degrees C) seemed safest for
      breast milk storage, short-term storage in a freezer is not recommended due to
      likely the hazards of the thawing process.

PMID- 11320772
TI  - Thyroid status and the levels of thyroid auto-antibodies in the sera of
      hyperthyroid and goitrous subjects.
AB  - OBJECTIVES: To determine the prevalence of thyroid auto-antibodies in specimens
      sent to Parirenyatwa hospital laboratory for thyroid function testing and to
      compare the thyroid status of these patients with that of apparently healthy
      subjects. DESIGN: Cross sectional study. SETTING: Immunology and radio
      immunoassay laboratories, Parirenyatwa hospital, Department of Chemical
      Pathology, and Blood Transfusion Services, Harare. SUBJECTS: 212 blood samples
      submitted for thyroid function testing and 230 blood samples from apparently
      healthy blood donors. MAIN OUTCOME MEASURES: Serum concentrations of free
      triiodothyronine (FT3), thyroxine (FT4), thyrotropin (TSH), and thyroid auto
      antibodies; anti microsomal (M Ab) and antithyroglobulin (Ag Ab) antibodies.
      RESULTS: The hyperthyroid subjects had median serum TSH level of 0.027 mIU/L (Q1
      = 0.006, Q3 = 0.052), median serum FT3 level of 15.895 pmol/L (Q1 = 10.563; Q3 =
      30.111), and a median serum FT4 level of 45.513 pmol/L (Q1 = 30.256; Q3 =
      63.910). The goitrous subjects had median serum TSH level of 0.390 mIU/L (Q1 =
      0.157; Q3 = 0.745). The blood donor group had median TSH value of 0.724 mIU/L (Q1
      = 0.471; Q3 = 1.170). (Normal ranges: TSH = 0.167 to 2.80) Amerlite TSH-30
      diagnostic kit; FT3 = 3.4 to 7.2 pmol/L; FT4 = 11 to 24 pmol/L) Amelex-MAB
      diagnostic kits) Thirty nine percent of the hyperthyroid subjects had either
      positive M Ab or Tg Ab or both. None of the goitrous subjects and the blood
      donors tested positive for neither M Ab, nor Tg Ab. No significant difference was
      found between the blood donors and the goitrous subjects for serum FT4 (P =
      0.51). However, significant differences were found between the goitrous, the
      blood donor and the hyperthyroid groups with regards to serum TSH, serum FT4, and
      serum FT3 levels (p = 0.001). CONCLUSION: Our findings indicate that the
      occurrence of thyroid auto-antibodies among the blood donors and the goitrous
      population was uncommon, but high in the hyperthyroid subjects. The increase of
      iodine intake through iodine prophylaxis could have had the side effects of
      iodine induced hyperthyroidism.

PMID- 11320773
TI  - Rational drug use (II): Hospital drug and therapeutics committees.

PMID- 11320774
TI  - Meaning follow up in Africa: myth or reality?

PMID- 11320775
TI  - Cigarette smoking, blood pressure and serum lipids and lipoproteins in middle
      aged women.
AB  - The relationship of cigarette smoking with blood pressure and serum lipids and
      lipoproteins was studied in the 3934 middle-aged women aged 40 to 59 years. After
      adjusting age, body mass index (BMI), alcohol intake and physical activity
      scores, the mean systolic and diastolic blood pressures (SBP and DEP,
      respectively) did not indicate dose-dependent relationships. The largest
      significant mean differences in SBP (4.6 mmHg), DBP (3.9 mmHg), high density
      lipoprotein cholesterol (HDL-C) (9.6 mg/dL), ratio of total cholesterol to HDL-C
      (TC/HDL-C) (0.8), triglycerides (TG) (22.9 mg/dL) and the logarithmic
      transformation of TG (Log TG) (0.26) were found between the non-smokers and
      smokers. When age, BMI, alcohol intake and physical activity scores were included
      in the forward stepwise multiple regression analyses, there were negative
      relationships found for cigarette smoking and SBP, DBP and HDL-C and positive
      relationships for cigarette smoking and TC/HDL-C, TG, Log TG and low density
      lipoprotein cholesterol. Although the results are somewhat variable, the present
      study shows cigarette smoking is negatively associated with SBP and DBP and
      unfavorably associated with serum lipids and lipoproteins in middle-aged women.

PMID- 11320776
TI  - Japanese and Korean elderly people's evaluation of clothing colors for elderly
      people.
AB  - This study evaluated the clothing colors in the elderly. We took photos using the
      elderly as models, displayed them on a computer screen, and produced 75 colors of
      the clothing in the elderly using computer graphics. The 75 colors were evaluated
      by Japanese and Korean elderly women. We compared the ideal colors for and the
      colors actually worn by elderly people in Japan and Korea. Japanese and Korean
      elderly women differed concerning their ideal clothing color and their most often
      worn color. The images concerning clothing colors also differed between the two
      groups, suggesting differences in their views related to clothing. Japanese
      elderly women tended to view clothing as a means of expressing their
      individuality, while Korean elderly women tended to view clothing as a means of
      expressing their character.

PMID- 11320777
TI  - The influence of posture change on measurements of relative body fat in the
      bioimpedance analysis method.
AB  - The purpose of this study was to clarify the influence of posture change on
      relative body fat in the bioelectrical impedance analysis (BIA) method. The
      subjects were 30 Japanese healthy young adult males (age: 19.8 +/- 1.4 years,
      height: 172.3 +/- 5.8 cm, weight: 67.1 +/- 8.2 kg). We used devices with
      different body segment inductions, between the hand and foot (H-F BIA) and
      between hands (H-H BIA), and set four measurement conditions differing in posture
      (supine or sitting), during rest and measurement. The reliabilities of %BF in the
      H-H and H-F BIA methods were very high (r = 0.995, 0.966), and the relationship
      in %BF between the UW method and each BIA method was mid-range (r = 0.767,
      0.709). Although there were no differences in %BF among different measurement
      postures in the H-F BIA method, %BF in the H-H BIA method increased significantly
      when the posture was changed just before measurement. This indicated that it is
      necessary to pay attention to the posture change just before measurement in the H
      H BIA method.

PMID- 11320778
TI  - Quantitative EEG data and comprehensive ADL (Activities of Daily Living)
      evaluation of stroke survivors residing in the community.
AB  - The purpose of this study was to investigate the hypothesis that EEG values match
      other comprehensive activities of daily living (ADL) evaluations between stroke
      survivors and normal controls. Various functions related to ADL were examined by
      means of ADL assessments (Measurement of Competence in the Elderly Living at
      Home, Barthel Index, Stroke Impairment Assessment Set, time needed to walk 10
      metres) and biosocial synchronization (the questionnaire on biosocial rhythms of
      daily living). EEG was undertaken using a computer-assisted portable EEG
      recorder. The power spectra were computed using a fast Fourier transformation
      analysis (FFT). The absolute and relative powers (percent of the total EEG power)
      of 5 frequency bands (delta, theta, alpha 1, alpha 2 and beta) and the peak
      frequency were analyzed. In comparing stroke survivors and the independent
      elderly, the latter had higher scores than the former in assessments of various
      functions related to ADL. The absolute and relative power of the delta band were
      lower in normal controls, and the relative power of the alpha (2) band and the
      peak frequency were higher than those of stroke survivors. Among the correlations
      between EEG and ADL assessments, the absolute and relative power of the alpha (2)
      band correlated significantly with ADL assessments of stroke survivors with right
      hemiplegia. The peak frequency was significantly increased in cases with high ADL
      scores. In conclusion, significant correlations were identified between the
      quantitative EEG data of stroke survivors in the chronic stage, living in the
      community, and ADL-related functions. Computer-assisted portable EEG recording is
      a potentially useful screening tool for objectively evaluating the functional
      levels of stroke survivors in field work.

PMID- 11320779
TI  - Cigarette smoking, blood pressure and serum lipids in Japanese men aged 20-39
      years.

PMID- 11320780
TI  - The effects of hedonic properties of odors and attentional modulation on the
      olfactory event-related potentials.
AB  - The purpose of this study was to investigate the influence of the hedonic
      properties of odors and the attention of subjects on components of the olfactory
      event-related potentials (OERP). The subjects were seven healthy male students.
      Two odors (orange and eugenol) of different hedonic properties were presented to
      the subjects via a constant-flow olfactometer during an oddball paradigm under
      ignore and attend conditions, and the OERP were then established. The latencies
      of the OERP were not affected by the qualitatively different odors, whereas the
      amplitude of late positive component (P3) during the presentation of orange was
      significantly larger than that during the presentation of eugenol. On the other
      hand, the allocation of a subject's attention led to a decrease in the latency
      and to an increase in the amplitude of P3. Moreover, the amplitude of P3
      increased significantly when the pleasant odor (orange) in the rare stimulus was
      presented under the attend condition. These results suggested that hedonic
      property, distribution of attention, and the interaction between these factors
      may influence the OERP components.

PMID- 11320781
TI  - [Fruitful mixture between quantitative and qualitative research. But the
      definition of evidence-based medicine could have been better prepared].

PMID- 11320782
TI  - [Long way from evidence to clinical recommendations].

PMID- 11320783
TI  - [Qualitative research methods in clinical practice].
AB  - Evidence-based medicine (EBM) corresponds to the physician's ambition to
      integrate his/her experience with the best current scientific knowledge, applying
      this integrated proficiency to clinical problems. The concept of EBM has become
      widely accepted and given rise to a global network usually emphasizing the
      randomized clinical trial (RCT) as the most important scientific method. However,
      clinical situations are very complex. To a greater or less extent they are all
      composed of diverse factors, ranging from bio-medical ones to inter-subjective
      relations, values and beliefs. In addition to RCT and other quantitative
      procedures, qualitative scientific methods could be used to explore complex
      clinical problems. Clinical problems always deserve to be addressed from various
      perspectives. Unfortunately, RCT has acquired such a dominant position as to give
      the impression that it is the sole preferred method within the EBM framework.
      Based on three examples, the present article claims that it is the questions
      asked by an investigation that should determine one's choice of methods, not the
      reverse. Consequently, we argue that it is important to remember that RCT is just
      one out of several potential scientific methods. The respective utility of any
      one method depends on the clinical issue at hand.

PMID- 11320784
TI  - [Evidence on hallux valgus. Weak scientific basis for treatment of a common
      complaint].

PMID- 11320785
TI  - [Cochrane meeting in South Africa: evidence-based medicine meets the third
      world].

PMID- 11320786
TI  - [Consumption of psychopharmaceuticals in residential facilities for the elderly.
      Evaluation of the extent, indications and effects].
AB  - Previous studies have shown a high level of consumption of psychopharmacological
      drugs in nursing homes. A questionnaire study in Kronoberg County in the autumn
      of 1998 investigated treatment with psychopharmacological drugs at ten nursing
      homes with a total of 405 care recipients. The questionnaire included questions
      about the extent of treatment, indications, duration of treatment and evaluation
      routines. Some 59% of the recipients, with a variation of 48-73% in different
      homes, were in continuous treatment with psychopharmacological drugs.
      Disturbances of sleep, depression and anxiety accounted for 79% of all
      indications. For 84%, treatment duration was not time-limited ("until further
      notice"). Assessments by the care staff were the most common evaluation
      procedure. In only 43% of cases were patients' self-evaluations heeded.
      Neuroleptics were probably overused, often with indications other than psychotic
      symptoms. Repeated treatment evaluations involving different categories of staff
      are important if excessive medication is to be avoided.

PMID- 11320787
TI  - [Multidisciplinary investigation is best for children with learning disabilities.
      Too critical attitude to diagnoses can keep the disorders hidden].
AB  - This article presents evidence of the importance of multidisciplinary assessment
      of students with learning disabilities. Multidisciplinary collaboration between
      different professions provides a more complete picture of each person's unique
      requirements, thereby facilitating more appropriate teaching. A critical attitude
      toward diagnosing students with learning disabilities may result in exaggeration
      of psychosocial problems, thereby running the risk that genuine learning
      disabilities, neurological problems or other disorders are being overlooked.

PMID- 11320788
TI  - [Work disability--a problem of many dimensions. Careful analysis can facilitate
      understanding].
AB  - Discrepancies between patients' and medical doctors' perceptions of disability as
      a result of illness and impaired function, respectively, is common in clinical
      practice. The evaluation of chronic pain is complicated, especially in a
      transcultural context. A multi-dimensional diagnostic schedule used at a health
      care center in a multiethnic community is discussed here. It encompasses somatic
      and psychiatric health, psychosocial pressure, social adaptation, pain
      communication, attitudes toward pain, and current place of employment. This
      schedule is used by two primary care physicians who assess patients' ability to
      participate in work and the extent to which their ability might be reduced.

PMID- 11320790
TI  - [A historical note on CRP in myocardial infarction. Old pioneer work should be
      noticed in the current debate].

PMID- 11320789
TI  - [Task and task time should dictate the choice of gloves in health care services].
AB  - Worldwide consumption of medical gloves increased during the 1980's due to the
      recognized risk of cross infections in medical and dental care. In Stockholm
      County Council around 1 million pairs of surgical gloves and 18 millions pairs of
      examination gloves are purchased per year. In the following paper different glove
      materials and types are presented and also regulations on use and purchase. The
      protective capacity of gloves and contact hypersensitivity reactions are also
      discussed and advice is provided on glove usage.

PMID- 11320791
TI  - [How to understand the world? An epilogue to the five "frog explanations"].

PMID- 11320792
TI  - [Breast cancer mortality: Is the effect of screening affected by participation
      and hormone therapy?].

PMID- 11320793
TI  - [Time for national guidelines on do-not-resuscitate decisions].

PMID- 11320794
TI  - [Insufficient standardization of blood pressure measurements is a serious source
      of error].

PMID- 11320795
TI  - [Reply: Yes, the recommendation should be to measure blood pressure with patients
      sitting].

PMID- 11320797
TI  - [Regionalization is good--also for health care services].

PMID- 11320796
TI  - [(Pseudo)croup, air humidification and choice of steroids].

PMID- 11320798
TI  - [Reply: Isaksson mixes up the cards].

PMID- 11320799
TI  - [Why there are not more physicians among blood donors?].

PMID- 11320800
TI  - [Fibromyalgia--reality or fantasy?].

PMID- 11320801
TI  - [Doubtful advertisement on an antiepileptic agent].

PMID- 11320802
TI  - Schizophrenic patients' normative needs for community-based psychiatric care: an
      evaluative study throughout the year following hospital release in the Dresden
      region.
AB  - BACKGROUND: The present study is part of a public health research project that
      evaluates restructured psychiatric community care for chronic patients in Saxony
      after the German reunification. It focuses on the analysis of the individual
      (expert-based) normative needs for mental health care of chronic schizophrenic
      patients in the Dresden region. METHOD: A cohort of ICD-10 chronic schizophrenic
      patients (n = 115) was examined at 1, 6 and 12 months after hospital release
      using the Needs for Care Assessment. RESULTS: Schizophrenics' normative needs for
      care in the clinical sector are dominated by positive and negative symptoms,
      psychopharmacological side effects and psychosocial distress. In the social
      realm, problems dealing with the management of household affairs, recreational
      activities, household chores, occupation and communication skills are the most
      frequent areas of need. In the Dresden region, considerable deficits apparently
      persist in the subsections "recreational activities" and "occupational and
      communication skills", which can be ascribed to the lack of appropriate
      institutions of care in the area. Schizophrenic patients' normative needs for
      care cannot be determined simply on the basis of a few, quickly identifiable
      markers. Individualized analysis is needed that incorporates variables pertaining
      to psychopathology, subjective coping, social competence, and the course of the
      disorder. The development of the needs for care over the period of 1 year can be
      predicted by trends in the social realm that are already visible within the first
      months. CONCLUSIONS: Community-based care offers available for schizophrenic
      patients in the studied region are by no means generally insufficient. Identified
      deficits in focal fields of social skills and rehabilitation must be minimized to
      meet international standards. This is of special importance because social
      impairments/disabilities predominate over the entire spectrum of schizophrenics'
      normative needs for psychiatric care.

PMID- 11320803
TI  - Predictors of social relations in persons with schizophrenia living in the
      community: a Nordic multicentre study.
AB  - BACKGROUND: Deinstitutionalisation has led to persons with serious mental illness
      spending most of their time outside psychiatric institutions. Not much is known
      about their social life. The paper presents the results of structured interviews
      with non-institutionalised persons with schizophrenia about treatment, care and
      social network. The network data are analysed from three perspectives: finding
      predictors of the number and of the quality of social contacts, and establishing
      the respective variables that characterise persons with high, and those with low,
      scores on both the quantity and quality dimensions of social integration.
      METHODS: Random samples of persons with schizophrenia receiving outpatient
      services in ten psychiatric centres in the four Nordic countries were
      interviewed. The following instruments were used: Interview Schedule for Social
      Interaction (ISSI), Camberwell Assessment of Needs, Lancashire Quality of Life
      Profile, General Assessment of Functioning (GAF) and Brief Psychiatric Rating
      Scale (BPRS), in addition to a checklist covering the utilisation of different
      services. The ISSI provided the main data for this paper. A restricted number of
      possible predictors were used in General Linear Model (GLM) factorial analysis
      and discriminant analysis. RESULTS: A total of 418 persons took part in the
      study. The overall participation rate was 55%. Social integration in terms of
      number of contacts was related to a high GAF score, few BPRS negative and
      hostility symptoms, having contact with user organisations and living in urban
      (in contrast to rural) areas. Availability of emotional relations was predicted
      by female sex, low scores on the BPRS hostility dimension, high GAF score, having
      contact with one's family more than once a month, and living in urban areas.
      Work, adequate leisure activities and GAF score discriminated between the best
      and worst integrated groups. CONCLUSIONS: Living in urban areas, being female,
      having a high GAF score and low scores on hostility predicted better integration
      in terms of number of contacts and emotional relations.

PMID- 11320804
TI  - A1 Ain Community Psychiatric Survey. I. Prevalence and socio-demographic
      correlates.
AB  - BACKGROUND: Psychiatric community studies are essential for the planning and
      development of psychiatric services, as well as being helpful in examining the
      socio-demographic correlates of mental disorders in a given community. Few such
      studies have been carried out to date in the Arabian peninsula. This paper forms
      part of a multipurpose community psychiatric survey conducted in A1 Ain in the
      United Arab Emirates. The findings regarding lifetime prevalence and psychiatric
      morbidity are reported. METHODS: A total of 1394 (n = 1394) adults systematically
      sampled from Al Ain community were assessed with a modified version of the
      Composite International Diagnostic Interview (CIDI) as well with other
      instruments: the new screening psychiatric instrument, Self-Reporting
      Questionnaire (SRQ-20), and the Structured Clinical Interview for DSM-IV Axis 1
      disorders (SCID) screening module. Lifetime prevalence and 1-week prevalence
      rates of mental distress as measured by screening instruments were estimated as
      well as the lifetime prevalence rate of CIDI ICD-10 psychiatric disorders. The
      sensitivity of the CIDI interview to correctly pick up distressed subjects, as
      well as those who had undergone previous treatment for a psychiatric disorder,
      was also calculated. Associations between socio-demographic risk factors and ICD
      10 psychiatric disorder as well as with mental distress were also examined by
      bivariate and multivariate analyses. RESULTS: Overall lifetime prevalence of ICD
      10 psychiatric disorder was found to be 8.2% (95% CI: 6.7-9.7), while the 1-week
      prevalence rate of mental distress as measured by the SRQ-20 was 15.6% (95% CI:
      11.8-19.5) and the lifetime prevalence rate of mental distress as measured by the
      new screening instrument was 18.9% (95% CI: 11.5-25.9). The CIDI interview
      correctly picked up 42% of subjects who had received previous psychiatric
      treatment and 51% of the distressed. Mood disorders and anxiety (neurotic)
      disorders were more common in women and alcohol and substance use disorders were
      exclusively confined to men. Female sex, young age, quality of marital
      relationship, life events over past year, chronic life difficulties, physical
      illness, family history of psychiatric disorders and past history of psychiatric
      treatment were found to be significantly associated with ICD-10 psychiatric
      disorder. Multivariate analysis revealed that age, sex, exposure to chronic
      difficulties and past history of psychiatric treatment were the most significant
      predictors of ICD-10 psychiatric disorders, and exposure to chronic difficulties,
      past history of psychiatric treatment and educational attainment were the
      significant predictors of lifetime ever and current mental distress. CONCLUSION:
      The pattern and trend of psychiatric morbidity found in this survey is in line
      with those reported by other surveys that utilized similar assessment
      instruments. Differences in rates are explained by different methodologies used.

PMID- 11320805
TI  - Excess mortality of suicide attempters.
AB  - BACKGROUND: Excessive mortality of suicide attempters has emerged from many
      follow-up studies. Completed suicide is the main cause of excess deaths, but the
      increased risk of deaths from other unnatural and natural causes is also of major
      public health concern. We lack follow-up studies of the different causes of death
      in cohorts of suicide attempters. The present study aimed to determine the
      mortality by suicide and other causes of death and to investigate risk factors.
      METHODS: This mean 5.3-year follow-up study was based on an unselected cohort of
      suicide attempts by both violent and non-violent methods, treated in hospitals in
      a well-defined urban catchment area in Helsinki. In total, 2782 patients aged 15
      years and over admitted to the emergency rooms after suicide attempt between 1989
      and 1996 were included in the follow-up analysis. Standardised mortality ratios
      (SMR) for suicide, disease, accident, homicide, and undetermined death were
      calculated. RESULTS: Mortality from all causes was 15 times higher than that
      expected among men and nine times higher in women. SMRs in men were 5402 (95% CI
      4339-6412) for suicide, 2480 (95% CI 925-4835) for homicide, and 11,139 (95% CI
      6884-16,680) for undetermined cause, and for women 7682 (95% CI 5423-9585), 3763
      (95% CI 52-5880) and 15,681 (95% CI 6894-22,294), respectively. Fifteen percent
      of all suicide attempters died during the average 5.3-year follow-up of the index
      attempt. Deaths from suicide accounted for 37% of all excess deaths in men and
      44% in women. The mortality ratio was highest during the 1st follow-up year. The
      total number of lost years of life among the 413 suicide attempters who died
      during follow-up was 13,883. The risk factors for all causes of death were male
      sex, single, retirement, drug overdose as a method, an index attempt not
      involving alcohol, and a repeated attempt. CONCLUSION: A suicide attempt
      indicates a severe risk of premature death, and suicide is the main cause of
      excess deaths. However, it appears that concentrating efficient treatment only on
      the most suicidal patients could prevent no more than two of five premature
      deaths. More effort is therefore needed to prevent the excess mortality of
      suicide attempters by also addressing causes of death other than suicide.

PMID- 11320806
TI  - The Lancashire Quality of Life Profile: modification and psychometric evaluation.
AB  - BACKGROUND: Although widely used in Europe, the conceptual and psychometric
      qualities of the Lancashire Quality of Life Profile (LQoLP) have not been
      thoroughly examined. Four issues need attention: coverage, scale construction,
      systematic missing data, and psychometric properties. METHOD: Concept mapping was
      used to examine the coverage, and exploratory factor analysis to examine the
      empirical scale structure of the LQoLP. Data of 518 long-term patients from ten
      different mental health care settings were used. Modifications to the LQoLP were
      proposed on the basis of these findings, and its psychometric properties were
      tested. Thirty-one respondents participated in a test-retest reliability study
      (T1-T2: 2 weeks). RESULTS: The modified LQoLP covers the quality of life-concept
      in a more comprehensive manner. Internal consistency, test-retest reliability and
      validity are good. CONCLUSIONS: The modified version of the LQoLP now covers ten
      domains, paying specific attention to patients' definition of quality of life
      (autonomy, coping, self-worth). Domains are now based on factor analysis. The
      problem of systematic missing data is solved. Psychometric properties are good.
      Because of moderate alphas, two domains need further investigation.

PMID- 11320807
TI  - DSM-IV and ICD-10 generalized anxiety disorder: discrepant diagnoses and
      associated disability.
AB  - BACKGROUND: It is commonly assumed that diagnoses according to DSM-IV and ICD-10
      are equivalent. Recent discussions on generalized anxiety disorder (GAD) have
      suggested that ICD-10 criteria may be identifying a milder form of the disorder
      than DSM-IV. This report examines prevalence and associated disability of DSM-IV
      and ICD-10 GAD. METHODS: The Composite International Diagnostic Interview was
      administered to a community sample of 10,641 people, and the diagnostic criteria
      that contributed to discrepancies between DSM-IV and ICD-10 GAD were identified.
      A multiple linear regression analysis was carried out to determine the strength
      of the relationship between disability, as measured by the SF-12, and discrepant
      diagnoses of GAD. RESULTS: The concordance between DSM-IV and ICD-10 GAD was fair
      (kappa = 0.39). The two sources of discrepancy when DSM-IV was positive and ICD
      10 was negative resulted from the requirement in ICD-10 that the respondent
      endorse symptoms of autonomic arousal (ICD-10 criterion B) and the requirement
      that ICD-10 GAD does not co-occur with panic/agoraphobia, social phobia or
      obsessive-compulsive disorder (ICD-10 criterion C). The two major sources of
      discrepancy when ICD-10 was positive and DSM-IV was negative resulted from the
      requirement in DSM-IV that the worry be excessive (DSM-IV criterion A) and that
      it causes clinically significant distress or impairment (DSM-IV criterion E). DSM
      only GAD cases had significantly higher levels of disability than ICD-only cases
      of GAD after controlling for demographic variables and the presence of comorbid
      psychiatric disorders. CONCLUSIONS: While the prevalence rates for DSM-IV and ICD
      10 GAD are almost identical, these classification systems are diagnosing
      different groups of people.

PMID- 11320808
TI  - [Neuroprotection. Bases and possibilities of a future clinical use].

PMID- 11320809
TI  - [The effect of gabapentin and gabapentin-lactam on retinal ganglion cell
      survival. Situation after acute retinal ischemia in animal models].
AB  - BACKGROUND: Reduction in the excitatory and potentially toxic neurotransmitter
      glutamate can protect retinal ganglion cells. What are the effects of the
      antiepileptic drug gabapentin, for which antiglutamatergic effects have been
      described, and the new substance gabapentin-lactam (GBP-L) on retinal ganglion
      cell survival after retinal ischemia? METHODS: In 3 groups of 10 rats each,
      ischemia was induced by elevating the intraocular pressure of the left eye to 120
      mmHg for 1 h. Saline, gabapentin (2 x 50 mg/kg intraperitoneally) and GBP-L (2 x
      50 mg/kg intraperitoneally) were injected before and 5 h after ischemia. Two
      weeks later ischemic damage was quantified histologically by counting the number
      of neurons in the ganglion cell layer. In vitro transmitter release experiments
      were performed to obtain information on the effect of gabapentin and GBP-L on
      ischemia-induced glutamate release and the mechanism of action of GBP-L. RESULTS:
      In the control group 17% of the retinal ganglion cells survived ischemia. GBP-L
      doubled the number of the surviving cells while gabapentin was not effective in
      these experiments. In vitro gabapentin and GBP-L reduced ischemia-induced
      glutamate release by 35.7% and 42.5%, respectively. The blockade of ATP-sensitive
      potassium channels antagonized the effect of GBP-L completely. CONCLUSION: GBP-L
      is neuroprotective in retinal ischemia and diminishes the release of the
      excitatory neurotoxic amino acid glutamate. The effect of GBP-L might be mediated
      by ATP-sensitive potassium channels. Also gabapentin reduced glutamate release
      but was not neuroprotective in vivo.

PMID- 11320810
TI  - [Retinal degeneration. Apoptosis as pathomechanism and therapy strategy].
AB  - Molecular techniques in ophthalmology and related subjects have led in recent
      years to the identification of many genes expressed in photoreceptor cells and
      have allowed the characterization of mutations leading to distinct phenotypes of
      retinal degeneration. Programmed cell death, or apoptosis, has been identified as
      the final common pathway in this disease group. A cascade of events has evolved,
      starting with specific stimuli and developing over different mediators and
      regulators (e.g., Fas ligand, proteins of the Bcl-2 family, p53) to effector
      enzymes (caspases). The ever increasing data of this pathway serve as a basis for
      new therapeutic strategies. We review the current knowledge on apoptosis in
      retinal degeneration.

PMID- 11320811
TI  - [Pilot study of pattern-electroretinographic changes in the DBA/2NNia mouse.
      Animal model of congenital angle-closure glaucoma].
AB  - PURPOSE: The aim of this study was to document the time-course of retinal
      dysfunction by pattern-electroretinography (PERG) in eyes of the DBA/2NNia
      substrain of mouse that develop an inherited angle-closure glaucoma. METHODS:
      Twelve DBA/2NNia mice and 12 control C57BL/6 J mice were studied by PERG
      recordings from 2 to 10 months of age. PERGs were recorded using different
      spatial and temporal frequencies. RESULTS: PERGs recorded with a temporal
      frequency of 7.5 Hz and a spatial frequency of 0.4 cycles/degree performed best
      to discriminate between DBA/2NNia mice and C57BL/6 J mice. When compared with
      normal C57BL/6 J mice, significant amplitude reductions of the PERG (Student's t
      test; p < 0.01) were found in DBA/2NNia mice by 5 months of age and continued to
      decline as the animals aged. At beginning of follow-up, the mean PERG amplitude
      in DBA/2NNia mice was 2.3 +/- 0.5 microV. At 5 months of age, the mean PERG
      amplitude was reduced by 0.9 +/- 0.45 microV (paired t-test; p < 0.0001).
      CONCLUSION: Previously, a significant loss of retinal ganglion cells was found in
      the DBA/2NNia mouse substrain at 6-7 months of age. In the present study, we
      found decreases in PERG amplitudes, occurring from the age of 5 months onward.
      Similarities with the findings in human glaucoma indicate the relevance of this
      animal model for further glaucoma research.

PMID- 11320812
TI  - [Combined cataract-glaucoma surgery with deep sclerectomy. An alternative to
      gonio-trephination in the intra- and early postoperative phases].
AB  - BACKGROUND: We examined the value of deep sclerectomy combined with
      phacoemulsification as a surgical technique in the peri- and postoperative
      phases. MATERIALS AND METHODS: Deep sclerectomy with phacoemulsification was
      carried out in 18 patients. Mean postoperative follow-up was 7.5 weeks. RESULTS:
      Deep sclerectomy was more difficult to perform than goniotrephination. We
      observed neither fibrin reaction nor hypotonic dysregulation (intraocular
      pressure, IOP, < 8 mmHg). Five patients required additional pressure-lowering
      drugs during postoperative IOP regulation. CONCLUSION: We consider the low
      inflammatory response in the early postoperative phase to outweigh the greater
      surgical difficulty and prolonged surgery time. Further studies must verify
      whether higher IOP during the early postoperative phase is sufficient for good
      long-term IOP regulation.

PMID- 11320813
TI  - [Optoacoustic tissue alterations for optimizing laser cyclophotocoagulation.
      Transscleral detection of laser-induced optoacoustic pressure transients].
AB  - BACKGROUND: Considerable problems occur in transscleral laser
      cyclophotocoagulation concerning energy dosage. We investigated the feasibility
      of localizing the ciliary body by the detection of thermoelastic pressure
      transients and of supervising on-line the degree of tissue damage during
      treatment. METHOD: We used a specially designed handpiece to apply short pulsed
      laser radiation with low energy levels to enucleated bulbs of rabbits. With an
      adjusted pressure transducer we examined acoustical transients generated in the
      area of absorption of the ciliary muscle or the pigmented epithelial layer and
      measured axial resolution of the method at various distances to the corneoscleral
      limbus. RESULTS: We detected acoustic transients that allowed rough localization
      of the target area. A marked change in signal was recorded with increasing level
      of ciliary destruction. CONCLUSION: This procedure can serve as an essential tool
      in the on-line supervision of the coagulation process. The laser parameters can
      thus be adjusted optimally to the progress of the treatment.

PMID- 11320814
TI  - [Age-related contractility of retinal arterioles during pure oxygen breathing].
AB  - BACKGROUND: Pure oxygen breathing is a non-invasive method to test the
      contractility of retinal arterioles. The normal response curve of this
      provocation method was tested using the Retinal Vessel Analyzer (RVA).
      Statistical analysis between groups was performed with th Man-Whitney test,
      correlations were tested with Pearsons' linear function. METHODS: After a 3-min
      baseline measurement 32 healthy volunteers breathed 100% oxygen for 5 min. The
      diameter of an retinal arteriole was measured continuously during this
      provocation by the RVA. Volunteers were separated into four groups according age.
      RESULTS: All four groups reacted to pure oxygen breathing with significant
      vasoconstriction of the retinal arteriole: in the youngest group (20-29 years)
      the reduction was 14.6 +/- 5.2% and the three older age groups 9.4 +/- 5.2%, 4.6
      +/- 2.7%, and 2.8 +/- 3.3%. The correlation between vasoconstriction and age was
      r = 0.73. CONCLUSIONS: Pure oxygen breathing is an easily performed method with
      minimal invasiveness to the patient. However, the age-correlated response curve
      must be kept in mind for the clinical use of this method.

PMID- 11320815
TI  - [Incidence of potential transmitters of Creutzfeldt-Jakob disease. A study of a
      collective of potential cornea donors].
AB  - BACKGROUND: The prevalence of Creutzfeldt-Jakob disease (CJD) is 1.5 cases per
      million persons. In addition to familial and sporadic forms, fewer than 5% of
      cases are due to iatrogenic transmission. Corneal transplantation has clearly
      been implicated as the origin of CJD in four cases. MATERIALS AND METHODS: We
      examined possible risks factors for corneal transplantation in material from 2545
      deceased patients at the University Hospital of Halle. RESULTS: Two patients had
      died of CJD or slow virus disease. Also in the 109 identified as being at higher
      risk of CJD no organs or tissues were harvested. CONCLUSION: We strongly
      recommend that patients at higher risk group of CJD, patients dying of CNS
      diseases of unknown origin and cause, and patients dying in psychiatric clinics
      be excluded from donating organ and tissue.

PMID- 11320816
TI  - [Pathologically reduced endothelial cell number despite normal slit-lamp
      microscopic corneal findings. An important result before cataract surgery].
AB  - BACKGROUND: A reduced number of endothelial cells increases the risk of corneal
      decompensation after cataract surgery. It is difficult to quantify the number of
      endothelial cells using slit-lamp microscopy since normal corneas may also show a
      reduced number of endothelial cells. MATERIALS AND METHODS: We compared the
      number of endothelial cells pre- and postoperatively in a group of 500
      consecutive patients. RESULTS: Corneas diagnosed preoperatively with corneae
      guttata by slit-lamp microscopy may reveal more than 1800 endothelial cells/mm2.
      These corneas may decompensate after surgery. CONCLUSION: We consider the routine
      use of endothelial microscopy to be a helpful diagnostic tool prior to cataract
      surgery.

PMID- 11320817
TI  - [Meeting the demand for quality and safety checked corneal transplants. The role
      of corneal banks and health care organizations in Germany].
AB  - Only cornea banks with organ culture techniques provide the substantial length of
      time often required by safety and quality controls of corneal transplants. In
      Germany the annual need would be 4,500 transplants per year, for which 7,500
      donor corneas must be primarily taken into culture. Meeting total demand should
      theoretically be easy as only 3,800 corneal donors are needed from a total of
      860,000 deceased per year. Since consent is given in up to 50% if approached
      properly, shortage in donor corneas should not pose a problem. However, shortage
      still is the major problem because most cornea banks are still in the initial
      phase. This is because of the lack of direct refinancing by health care
      organizations. These organizations must be required to meet their legal
      responsibilities in this area.

PMID- 11320818
TI  - [Clinical findings in autosomal recessive syndrome of blue cone
      hypersensitivity].
AB  - BACKGROUND: Intrafamilial variability of the syndrome of night blindness,
      maculopathy, and enhanced S-cone hypersensitivity was examined. PATIENTS AND
      METHODS: Siblings with a history of night blindness and reduced visual acuity
      were examined clinically, psychophysically, electroretinographically (ERG), and
      electro-oculographically (EOG). RESULTS: The siblings had had night blindness
      since early childhood and reduced visual acuity since the age of 20 years.
      Ophthalmoscopy showed degenerative, pigmented changes and subretinal spots, while
      one sibling had cystic lesions in the fovea. Scotopic ERG showed no rod-driven
      responses, while large, slow waveforms were detected in response to bright
      flashes. Photopic ERG induced responses similar in time, amplitude, and
      configuration to those of the dark-adapted ERG. The b-wave configuration was
      unchanged in response to chromatic stimuli. However, photopic ERG was more
      sensitive to blue and white than to red stimuli. The light peak on EOG was
      reduced. CONCLUSIONS: The enhanced S-cone sensitivity syndrome was expressed to a
      different degree of severity and probably inherited in an autosomal recessive
      mode. These unusual ERG findings may be due to a depressed rod system and an
      increased number of S-cone photoreceptors, postreceptoral circuits, and S-cone
      sensitive ganglion cells.

PMID- 11320819
TI  - [A differentiated study of the retinal function in segmental retinitis pigmentosa
      by multifocal electroretinograms].
AB  - PURPOSE: Generalized retinal degenerations such as retinitis pigmentosa may
      manifest with focal retinal dysfunctions. These may be detected objectively by
      new electrophysiological techniques, such as multifocal electroretinography
      (ERG). CASE REPORT: A mother and daughter, aged 81 and 46 years, showed bilateral
      caudal bone spiculae formations with corresponding cranial visual field defects
      in the static perimetry of the central visual field (Octopus) and in the kinetic
      perimetry (Goldmann). RESULTS: Pattern VEP, pattern ERG, EOG, and cone ERG were
      within the normal range. The scotopic ERG was in the lower normal range. The
      multifocal cone ERG of the central 50 degrees showed reduced amplitudes and
      prolonged latencies in the first-order response component. These findings
      corresponded to the area of the bone spiculae and the scotomata. CONCLUSION:
      Multifocal ERG enables the detection of focal retinal cone dysfunction in
      segmental retinitis pigmentosa. It is an additional tool that may aid in the
      diagnosis and classification of this disease.

PMID- 11320820
TI  - [Consistent IOL calculation].

PMID- 11320821
TI  - [Tumor of the eyebrow with extension into the orbit. An 85-year-old patient with
      progressive swelling in the area of the left eyebrow].

PMID- 11320822
TI  - [Juvenile glaucoma: a 17-year-old patient with liver transplantation].

PMID- 11320823
TI  - [Optic neuritis. First manifestation of multiple sclerosis? Current diagnostic
      and therapeutic strategies].

PMID- 11320825
TI  - Tubular e-PTFE implants in glottal and neoglottal insufficiency: tolerance and
      stability in an animal model.
AB  - The aim of our research is to develop a laryngeal tissue augmentation technique
      that will be useful in treating glottal and neoglottal insufficiency. In a
      previous study the feasibility of insertion of tubular expanded poly
      tetrafluoroethylene (e-PTFE) tissue implants into the larynx of a porcine model
      was demonstrated. In this paper we report the clinical, endoscopic, computed
      tomography (CT) and magnetic resonance image (MRI) and histopathological follow
      up findings. These results demonstrate host tolerance of the implant over the
      period of study (six months) with little tissue reactivity to tubular e-PTFE
      implants in the porcine model. The tubular shape of the implant enhances
      stabilization by the rapid and complete host tissue penetration of the implant's
      interstices, making tubular e-PTFE a potentially useful soft tissue augmentation
      material for laryngeal incompetence.

PMID- 11320824
TI  - Bacterial coating with immunoglobulins on the palatine tonsils during infectious
      mononucleosis: immunocytochemical study with gold markers.
AB  - Epithelial cells and bacteria were sampled from the tonsillar surfaces of seven
      patients (six males, one female; median age 16 years, range 10 to 21 years)
      suffering from acute infectious mononucleosis with concomitant
      pharyngotonsillitis. By using gold-labelled antiserum to human IgG and secretory
      IgA (sIgA), micro-organisms on the tonsillar surfaces coated with these
      immunoglobulins could be identified by tracing the gold particles in the
      transmission electron microscope. The patients harboured significantly fewer
      bacteria coated with immunoglobulins than did healthy controls. More bacteria
      were coated with IgG immunoglobulins than with sIgA. Reduced immunoglobulin
      coating of the bacteria on the tonsillar surfaces during infectious mononucleosis
      can explain their tendency to immense local colonization and proneness to
      penetrate into the epithelial cells.

PMID- 11320826
TI  - Clinical features of pharyngeal cancer: a retrospective study of 258 consecutive
      patients.
AB  - Pharyngeal cancer still presents an unsatisfactory mortality (30-40 per cent in
      most series, with a slightly better prognosis for nasopharyngeal cancer relative
      to both oropharyngeal and hypopharyngeal cancers) despite advances in treatment.
      Therefore, it is critical to know the clinical features of pharyngeal cancer. The
      purpose of this study was to investigate the most relevant clinical features of
      pharyngeal cancer (oropharyngeal, hypopharyngeal, and nasopharyngeal) in order to
      improve knowledge of this malignancy with the aim of ameliorating diagnosis and
      treatment. The retrospective study was based on a review of medical records from
      258 consecutive patients with pharyngeal cancer (oropharyngeal, hypopharyngeal
      and nasopharyngeal) diagnosed at La Paz University Hospital, Madrid, Spain,
      between January 1 1991 and and December 31 1995. Medical records were provided by
      the Departments of Otorhinolaryngology, Head and Neck Surgery, Radiation
      Oncology, and Medical Oncology. All medical records were analysed for the
      following clinical variables: 1) incidence, 2) sociodemographics, 3) sites
      (oropharynx, hypopharynx, nasopharynx) and subsites, 4) clinical and histological
      staging, 5) pathology, 6) presenting symptoms, 7) time to diagnosis, 8) patients'
      general performance status at diagnosis, 9) personal cancer history and
      synchronous head and neck tumours, 10) premalignant lesions, and 11) paediatric
      cases. Our most outstanding finding was the excessively long time that elapsed
      between first clinical manifestation appearance and conclusive diagnosis of
      pharyngeal cancer (4.7 months for pharynx, 4.5 for oropharynx, 4.4 for
      hypopharynx and 6.5 for nasopharynx cancers). It was found that nasopharyngeal
      cancer was quite different from both oropharyngeal and hypopharyngeal cancers
      with respect to its potential aetiology, risk factors and clinical presentation.
      In addition it has a better prognosis.

PMID- 11320827
TI  - Resident training in head and neck flap reconstruction in U.S. academic
      otolaryngology programmes.
AB  - The main objective of this study was to assess resident training in head and neck
      flap reconstruction, and to determine the confidence of graduating residents in
      performing these flaps independently. Questionnaires were distributed to
      otolaryngology residents graduating in 1997. Respondents recorded the number of
      pedicled and free flap procedures they performed, or assisted with, and indicated
      flaps they felt confident about performing independently. Pectoralis major
      myocutaneous (PMMC) (n = 560, mean 6.59) and radial forearm (RF) (66, 0.78) were
      the most common pedicled and free flaps performed. There was a significant
      difference (p = 0.0002, Mann-Whitney U test) between median confidence for
      pedicled (44.5 per cent) and free flaps (two per cent). Ten of the 17 flaps
      showed a significant Pearson correlation (p < 0.05) between number of procedures
      performed and confidence in performing them independently. Of the pedicled flaps,
      latissimus dorsi (LD) showed good correlation (r = 0.67), PMMC showed low
      correlation (r = 0.19) and other pedicled flaps fair correlation. Of the free
      flaps, LD (r = 0.64) and fibula (r = 0.50) showed good correlation and rectus
      abdominis and RF fair correlation. There was a fair inverse correlation (r = 
      0.29) between numbers of pedicled and free flaps performed. Higher correlation in
      flaps uncommonly performed reflects greater operative training necessary to
      achieve the confidence for performing these flaps independently. As respondents
      performed greater numbers of free flaps, the number of pedicled flaps decreased.
      It might thus be important to train residents in all aspects of pedicled flaps.
      Most respondents were of the opinion that additional training in free flaps was
      necessary for those planning a career in head and neck reconstructive surgery.

PMID- 11320828
TI  - Landmarks for parotid gland surgery.
AB  - Many surgical landmarks have been suggested to help the surgeon identify the
      facial nerve when performing parotid gland surgery. There is no conclusive
      evidence that any one landmark is better than the rest. In this study distances
      from the most frequently used surgical landmarks to the main trunk of the facial
      nerve were measured in 30 halves of cadaver heads. Two ENT surgeons assessed the
      best landmark in each case. The tympanomastoid suture was nearest to the main
      trunk and was therefore considered the most reliable landmark. Its average
      distance to the main trunk of the facial nerve was 2.7 mm. This result was
      consistent with the subjective best score given by two ENT surgeons.

PMID- 11320829
TI  - An improved instrument mounting arm.
AB  - Although some form of commercial instrument mounting arm is available, a paucity
      of information in the literature may cause problems in selecting the most
      appropriate model for an ENT department wishing to trial their invention for use
      in the clinic or operating theatre. The instrument mounting arm described here is
      based on existing designs used by hobbyists and model makers for many years but
      the main benefit of this innovation is its multi-purpose use in the operating
      theatre and cost effectiveness since it is made of aluminum alloy. It is compact,
      stable and easily adjustable and can incorporate an endoscope holder or an
      operating end piece to mount various ENT instruments that offers considerable
      advantages to the unassisted operator.

PMID- 11320830
TI  - Sudden bilateral hearing loss and sporadic mitochondrial DNA deletion.
AB  - Several studies have indicated that a number of different mitochondrial DNA
      (mtDNA) mutations may be responsible for human pathologies. Sensorineural Hearing
      Loss (SNHL) may be associated with known syndromes (syndromal SNHL) or represent
      the only manifestation of mitochondrial damage (non-syndromal hearing loss).
      Moreover, mtDNA alterations may be responsible for aminoglycoside-induced
      deafness. We describe a patient harbouring a single sporadic mtDNA deletion, who
      presented with sudden adult-onset bilateral, although non-simultaneous SNHL, that
      was partially responsive to corticosteroids. Increased values of rest, and
      exercise, blood lactic acid were decisive for diagnosis, prompting muscle biopsy
      that revealed the mtDNA deletion. The case underscores the importance of
      investigating a mitochondrial disease in cases of SNHL of unknown origin and
      points out the importance of an increased blood level of lactic acid as a
      screening test.

PMID- 11320831
TI  - Traces of perilymph detected in epipharyngeal fluid: perilymphatic fistula as a
      cause of sudden hearing loss diagnosed with beta-trace protein (prostaglandin D
      synthase) immunoelectrophoresis.
AB  - The incidence of perilymphatic fistula as cause of sudden hearing loss is not
      known. We present a case with sudden unilateral hearing loss associated with a
      positive beta-trace protein test of an epipharyngeal fluid sample. The patient
      presented with sudden sensorineural hearing loss on the right side. A stapedotomy
      had been performed nine months previously due to otosclerosis. Intravenous
      therapy for the treatment of sudden hearing loss was unsuccessful. At the time of
      sudden hearing loss, epipharyngeal fluid was collected using a Raucocel sinus
      pack. Investigation using rocket immunoelectrophoresis showed the presence of
      beta-trace protein. Upon repeating tympanoscopy there was no obvious labyrinthine
      fluid egress, but the oval window was sealed with fibrin sponge and fibrin glue.
      The patient's hearing improved over a period of five months.

PMID- 11320832
TI  - Osteolipoma of the skull base.
AB  - Although lipomas are the most common benign tumours of the head and neck, the
      involvement of the skull base is rare and it is also very rare for a lipoma to
      undergo osseous metaplasia to become an ossifying lipoma or osteolipoma. We
      present a case of a solitary osteolipoma involving the skull base in a 17-year
      old girl. A few cases of osteolipoma involving the head and neck have been
      reported, but this may be the first reported case of a solitary osteolipoma
      involving the skull base with extension to the infratemporal fossa and
      parapharyngeal space. The computed tomography (CT) scan helped to clinch the
      diagnosis and the histopathology confirmed it. The clinical presentation, role of
      CT scan, surgical approach used, histological features and the review of
      literature are discussed.

PMID- 11320833
TI  - Inflammatory myofibroblastic tumour of larynx.
AB  - Inflammatory myofibroblastic tumour (IMT) is a benign pseudoneoplastic
      proliferation, mainly developing in the lung and extremely rare in the larynx. A
      patient with a two-month history of dysphonia and a polypoid left true vocal fold
      tumour is presented. Histological and clinical knowledge of this lesion is
      important to exclude a misdiagnosis (e.g. malignant epithelial or mesenchymal
      tumours) and an inappropriate treatment.

PMID- 11320834
TI  - Post-tonsillectomy bleed: a delayed diagnosis of duodenal ulceration.
AB  - Post-operative haemorrhage is one of the commonest complications of
      tonsillectomy. We report a case of a 36-year-old lady who presented with three
      haemorrhagic episodes following tonsillectomy. Although initially treated as
      secondary tonsillar haemorrhage, the actual cause of the bleeding was later
      identified to be a duodenal ulcer. The case is presented with a review of the
      literature.

PMID- 11320835
TI  - 'Hairy polyp' of the pharynx in association with an ipsilateral branchial sinus:
      evidence that the 'hairy polyp' is a second branchial arch malformation.
AB  - The pharyngeal 'hairy polyp', or 'dermoid' has caused considerable debate as to
      its origin since the original classification proposed by Arnold in 1870. This
      classification implies that the hairy polyp is either a teratoma or sequestration
      dermoid cyst. Many papers contest this view, in favour of a developmental
      malformation. We describe the first case of a hairy polyp in association with an
      ipsilateral branchial sinus as further supportive evidence of a developmental
      malformation of the second branchial arch.

PMID- 11320836
TI  - Tongue-base hamartoma in tuberous sclerosis.
AB  - This paper describes the case of a 41-year-old female with tuberous sclerosis who
      presented with a large tongue-base hamartoma. The surgical management of the
      patient was complicated by the presence of a large thyroid goitre. Awake fibre
      optic intubation, thyroidectomy then tracheostomy were necessary before the
      tongue-base hamartoma could be safely resected. To the best of our knowledge,
      this is the first reported case of a tongue-base hamartoma in a patient with
      tuberous sclerosis.

PMID- 11320837
TI  - Neurofibromatosis type 1 of the head and neck: dilemmas in management.
AB  - Neurofibromatosis type 1 (NF 1) or Von Recklinghausen's disease is an autosomal
      dominant condition characterized by multiple skin cafe-au-lait lesions and
      multiple neurofibromas. In the head and neck neurofibromas have a predilection to
      arise in th deep planes of the neck. Surgical management is nearly always
      required for functional or cosmetic reasons or to exclude the possibility of
      malignant transformation. We present four cases of neurofibroma of the head and
      neck and illustrate the difficulties inherent in managing this condition,
      particularly the age range in which it may occur, the risk of malignant
      transformation, the possibility of abnormal bleeding and the morbidity that may
      be associated with the surgical resection. The role of magnetic resonance (MR)
      scan in the assessment and monitoring of these lesions is highlighted. We also
      report a unique association of a pharyngeal pouch with NF 1 in a young (25-year
      old) patient.

PMID- 11320838
TI  - Alveolar rhabdomyosarcoma of the parotid gland.
AB  - Alveolar rhabdomyosarcoma of the parotid gland is a rare condition. The treatment
      should involve an aggressive multi-modality approach incorporating surgical
      removal of the tumour, radiotherapy, and multi-agent chemotherapy. The
      presentation of this condition along with the most appropriate line of treatment
      is discussed.

PMID- 11320839
TI  - Ischaemic optic neuropathy following bilateral neck dissection.
AB  - Two cases of ischaemic optic neuropathy, which occurred as a complication of
      oncological neck surgery, are reported. These cases are submitted because of the
      apparent scarcity in the literature of this complication after head and neck
      surgery. They are also unusual because they presented with different clinical
      manifestations of ischaemic optic neuropathy after separate forms of bilateral
      neck dissection. A literature review identifies a small number of similar cases
      and risk factors and preventative measures are discussed.

PMID- 11320840
TI  - Mediastinal tuberculosis in a 10-month-old child.
AB  - We report a rare case of mediastinal tuberculosis in a child who presented as a
      possible inhaled foreign body. A 10-month-old girl was admitted with a five-month
      history of cough, wheeze and problematic feeding, thought initially to be due to
      asthma. A clinical deterioration and subsequent X-rays suggested an inhaled
      foreign body. However, at direct laryngotracheobronchoscopy no foreign body was
      found and subsequent investigations revealed a subcarinal mediastinal mass. She
      underwent a thoracotomy and excision of the mass, the histological analysis of
      which revealed it to be of tuberculous origin. When a patient presents with
      symptoms of upper airway obstruction which are highly suggestive of a foreign
      body, other causes such as mediastinal tuberculosis must be borne in mind when no
      foreign body can be found. Although rare, cases of tuberculosis are apparently
      increasing and the otolaryngologist must be aware of its various manifestations
      and submit specimens for appropriate analysis. We also briefly review mediastinal
      lymphadenopathy due to tuberculosis.

PMID- 11320841
TI  - Papillary squamous cell carcinoma of the larynx.
AB  - A case of papillary squamous cell carcinoma of the larynx in a 50-year-old man is
      reported. The lesion was located in the supraglottic region and grossly presented
      a characteristic finger-like pattern of growth. The tumour pursued an indolent
      clinical course, and the patient is well and free of disease after 47 months of
      follow-up. The present paper recapitulates the macro- and microscopic features of
      this rare neoplasm and stresses its differential diagnosis with other exophytic
      squamous cell carcinomas of the region.

PMID- 11320842
TI  - Epidemiology of basal cell carcinoma and squamous cell carcinoma of the pinna.
AB  - This is a retrospective study designed to compare the incidence of basal cell
      carcinoma (BCC) and squamous cell carcinoma (SCC) in the head and neck skin area
      with special reference to the pinna. The results showed 426 patients had 460
      cutaneous malignancies in the head and neck area, managed by four specialties
      (ENT, Dermatology, General Surgery and GPs) over the period 1994-99. The lesions
      comprised 375 (80.47 per cent) BCC and 85 (18.47 per cent) SCC. In cases of BCC
      the facial areas were commonly involved (88 per cent), whilst SCC was almost
      equally distributed between the most (face, forehead and nose) and least exposed
      areas (pinna and scalp). The overall ratio of BCC to SCC remained four to one in
      the head and neck area. In 41 patients with 51 lesions over the pinna there were
      29 (56.8 per cent) BCC and 22 (43.1 per cent) SCC hence the ratio was 1.3 to 1
      for this site. We conclude that in the case of a suspicious lesion over the
      pinna, the risk of SCC is comparatively much higher. With increasing awareness of
      early and quick diagnosis of cancer cases, it is recommended that these patients
      should be referred urgently to prevent the significant morbidity associated with
      invasive SCC.

PMID- 11320843
TI  - Improving standards in the treatment of acute otitis externa by the use of a
      treatment protocol and open access to aural toilet.
AB  - A prospective audit of the procedure and outcome in the management of acute
      otitis externa was undertaken in our unit. The first cycle demonstrated a
      heterogeneous approach and clinical isolation of junior staff. A questionnaire
      survey of local general practitioners highlighted clinical confusion over the use
      of topical medication and a need for improved access to facilities for aural
      toilet. General practitioner liaison and education was an essential component in
      formulating a change in practice. In particular, open access for aural toilet was
      introduced and utilization encouraged. Following changes in practice, the second
      cycle of the audit showed that treatment protocols were effective and adhered to
      by junior staff.

PMID- 11320844
TI  - Tympanometric findings in cleft palate patients: influence of age and cleft type.
AB  - Tympanometry was analysed according to cleft type with respect to age in 239
      cleft palate patients (57 with bilateral cleft lip and palate (BCLP)), 122 with
      unilateral cleft lip and palate (UCLP) and 60 with isolated cleft palate (ICP).
      The frequency of type B tympanograms was 46.5 per cent in the BCLP group, 50.6
      per cent in the UCLP group and 58.3 per cent in the ICP group. Type A
      tympanograms were more frequently observed in older patients (median age 11
      years) in comparison to type B (median age five years; p < 0.001) and type C
      (median age six years; p < 0.001). The total sample showed an age-related
      decrease in the frequency of type B tympanograms (rs = -0.3942; p < 0.001). The
      frequency of type A tympanograms increased significantly with age (rs = 0.4263; p
      < 0.001), whereas type C was not correlated with age. In the UCLP group, the
      frequency of type B tympanograms decreased with age (rs = -0.4430; p < 0.001),
      the decrease being faster than in the BCLP group (rs = -0.3186; p = 0.001) and
      the ICP group (rs = -0.3378; p < 0.0001)). Type B tympanograms had the highest
      correlation with a hearing loss of 21-40 dB at mean hearing level at speech
      frequencies (MHLSF) (rs = 0.4574; p < 0.001), a lower correlation with a hearing
      loss of 11-20 dB (rs = 0.2184; p = 0.02) and the lowest correlation with hearing
      loss above 40 dB. At the ages of one to three, the frequency of type B is higher
      in UCLP patients than in the BCLP and ICP groups, decreasing at seven to 12,
      increasing again at 13 to 15, and thereafter showing a continuous decrease. In
      the BCLP group, the frequency of type B increased significantly at the ages of
      four to six and then decreased continuously from seven to 18. In ICP patients,
      the changes in the frequency of type B with age are not significant until the age
      of 15; at the age of seven, it is higher than in the BCLP and ICP groups. The
      type C tympanogram is not typically found in cleft palate patients and its
      frequency is not correlated with age. It can be presumed that each type of cleft
      lip and palate, due to its characteristic conditions in the epipharynx, will
      favour a different mode of pathophysiological development of middle-ear disease.

PMID- 11320845
TI  - In vitro evaluation of a malleus head to stapes head 'incus replica' prosthesis.
AB  - An ossicular prosthesis produced by making a mould from a cadaveric incus and
      injecting ionomeric cement into it (incus replica prosthesis, IRP) has been
      cemented to the malleus head and stapes head and evaluated in fresh human
      temporal bones using a laser vibrometer. Stapes velocity was recorded under
      acoustic stimulation and foot plate displacements were derived. Fourteen
      frequencies between 125 Hz and 8000 Hz have been used. Measurements were made
      with the ossicular chain intact, following removal of the incus, with the
      prosthesis cemented to the malleus, but not the stapes, and with the incudo
      stapedial joint cemented. In a second series of experiments the performance of
      the IRP was compared with that of a Causse partial ossicular replacement
      prosthesis, using the same experimental set-up. The results indicate that the
      prosthesis performs almost as well as the intact ossicular chain and that
      cementing the incudo-stapedial joint gives better sound transmission than leaving
      it uncemented. In addition the IRP outperforms the conventional partial ossicular
      replacement prosthesis.

PMID- 11320846
TI  - [Hospital discharge report of patients with chronic obstructive pulmonary
      disease].
AB  - Chronic obstructive pulmonary disease usually doesn't require hospital admission.
      However, the course of the disease is characterized by frequent exacerbations
      that often require hospital admission, representing a good chance to define all
      aspects of chronic obstructive pulmonary disease and improve the management of
      the patient. When the patient is discharged from the hospital, an essential
      Report should specify the reasons of admission, the symptoms (e.g.: cough, sputum
      production and dyspnoea) and the findings of physical examination, the results of
      the main laboratory and radiological tests performed (pulmonary function tests
      are essential to define the severity of degree of airway obstruction and useful
      for its longitudinal assessment), the treatment administered, the final
      diagnosis, the suggested therapy, the follow-up appointments and the
      recommendations (nutrition, psychological support, muscle reconditioning) of a
      possible rehabilitation program.

PMID- 11320847
TI  - [Perspectives of gene therapy in ischemic syndromes of the lower limbs].
AB  - In recent years, new knowledge has been provided from the study of the biological
      mechanisms underlying the angiogenic process, i.e. the development of a new
      vasculature from preexisting blood vessels. These advances suggested a possible
      new approach for the therapy of peripheral obstructive arterial disease, based on
      the treatment of ischemic tissues with angiogenic growth factors. As demonstrated
      by experimental studies in animal models, a therapeutic effect can be reached as
      the newly formed vascular network, functioning as a biologic by-pass, restores a
      normal blood supply to the ischemic territories. New techniques of gene therapy
      proved effective in reaching sustained concentrations of angiogenic factors in
      the target tissues. This paper will briefly describe the methodological
      background, the results of the early clinical applications of angiogenic gene
      therapy and the open questions that need to be addressed before this new approach
      can be proposed as an effective option instead of existing medical and surgical
      therapies.

PMID- 11320848
TI  - [Predictive variables of mortality in elderly patients after hospitalization.
      Significance of multidimensional evaluation].
AB  - Functional status evaluation in the elderly is stronger predictor of hospital
      outcomes than type and number of pathology. Multidimensional and functional
      assessment among hospitalized elderly allows to identify, as well as acute and
      chronic illness, disabilities of sanitary problems and socio-economical aspects
      that in the elderly can complicate illness. Our study has identified six-month
      mortality post hospitalization of 20.2%. The high mortality observed in our
      follow-up agrees with the literature and it is a marker of considerable frailty
      among elderly patients. The independent predictor variables of six month post
      hospital mortality in the study were: male gender, dependence DMI score, low
      serum albumin (2.8 g/dl), impaired IADL score, cancer illness and APACHE score <
      13.7. These measures represent distinct domains: demographic, functional and
      clinical. Identifying predictors of high-risk patients is an important way in
      accurate targeting.

PMID- 11320849
TI  - [Therapeutic infusion of heparin. Application of a nomogram correlated with
      weight].
AB  - We performed a retrospective study to determine whether the use of a nomogram in
      General Medicine Wards is superior to the empiric method for the adjustment of
      heparin dosage. In the period october 1998-september 1999 we treated 138 patients
      with continuous infusion of heparin using a weight-based nomogram. Then we
      compared these data (nomogram group) with data from period october 1997-september
      1998, when we had treated 155 patients with heparin, using empiric method for
      dose adjustments (empiric group). The proportion of patients reaching the
      therapeutic aPTT 24 hours after the start of therapy was 90.5% in nomogram group
      compared with 56.1% in the empiric group (P < 0.001). The proportion of
      nontherapeutic and subtherapeutic aPTT was significantly reduced in the nomogram
      group (6.0% vs. 11.1%, P < 0.001; 13.7% vs. 19.3%, P < 0.001). Furthermore, in
      the nomogram group the proportion of consecutive nontherapeutic or
      overtherapeutic values were significantly reduced (0.1% vs. 2.2%, P < 0.001; 1.8%
      vs. 2.3%, P < 0.001). We conclude that a weight-based heparin nomogram adapted
      for own aPTT range is successfully used in General Medical Wards of a community
      hospital.

PMID- 11320850
TI  - [Cytomegalovirus chorioretinitis in a patient with orthotopic liver transplant.
      Role of virologic diagnosis and of antiviral chemoprophylaxis].
AB  - A case report of cytomegalovirus retinitis in a patient who underwent orthotopic
      liver transplantation, and suffered from a prior episode of systemic
      cytomegalovirus disease, is described. Although the diagnosis was obtained only
      when clinical symptoms prompted ophthalmoscopic evaluation, a successful outcome
      was attained after ganciclovir treatment. The role of clinical and virologic
      monitoring of organ transplant recipients, and that of primary and secondary
      chemoprophylaxis against cytomegalovirus infection are discussed, according to
      personal observations and to an updated literature review.

PMID- 11320851
TI  - [Acute cholestatic hepatitis caused by propafenone. Report of a case and review
      of the literature].
AB  - A case of acute cholestatic hepatitis associated with use of propafenone is
      reported. Hepatitis developed 3 weeks after the beginning of administration of
      this drug. The close time relationship between the administration of the
      antiarrhythmic drug and the acute onset of the liver damage, the exclusion of
      hepatobiliary disease and the rapid normalisation of biochemical parameters
      following withdrawal of the drug strongly suggest that propafenone was involved
      in the pathogenesis of this syndrome. Meticulous taking of patient history and
      clinical assessment are mandatory for the early identification of drug-induced
      hepatotoxicity and avoidance of more severe types of reactions, such as liver
      failure.

PMID- 11320852
TI  - [New strategies for the postsurgical treatment of malignant glioma].
AB  - Malignant gliomas are known for their intrinsic heterogeneity that contributes to
      tumour recurrence, despite aggressive multimodality therapy. New approaches of
      post surgical treatment are formulated, according to specific aspects of the
      biology of gliomas including angiogenesis, invasion, DNA-repair mechanisms, cell
      cycle regulation and apoptosis. Efforts are also done in order to define the use
      of currently available cytotoxic agents by combining them with so-called biologic
      modalities. Thus there has been a change in the concept of management of
      malignant gliomas focusing the aim in containing the tumour, rather than
      attempting a cure.

PMID- 11320853
TI  - [Hypertrophic cardiomyopathy and sudden death].
AB  - Hypertrophic cardiomyopathy is a primary and usually familial cardiac disorder
      characterized by a genetic, pathophysiologic and clinical complexity. The natural
      history of the disease is extremely heterogenous: many patients have no or mild
      symptoms and a near-normal longevity, some develop severe symptoms of heart
      failure, and others die suddenly often at a young age and in the absence of
      previous symptoms. Although sudden and unexpected cardiac death may occur at any
      age in hypertrophic cardiomyopathy, this devastating event is the most common
      modality of death in children and young patients. Despite intense investigation,
      risk stratification remains a major challenge. This paper examines the present
      knowledge on risk assessment and treatment strategies for the prevention of
      sudden death.

PMID- 11320854
TI  - [Estrogens and progestins in hormone replacement therapy in menopause].
AB  - Although the use of hormone replacement therapy for menopause based on estrogens
      alone increases endometrial cancer risk, several studies indicate that combined
      therapy with estrogens and progestins is not related to an appreciable excess of
      endometrial cancer risk, if progestins are given for more than 10 or 14 days in
      each cycle. Combined therapy, however, may be associated to greater excess in
      breast cancer incidence as compared to estrogens alone.

PMID- 11320855
TI  - [The return of thalidomide].
AB  - Nearly four decades after its withdrawal from the marketplace because of the
      discover of its teratogenicity, the thalidomide is now attracting a renewed
      interest due to the identification of its important anti-inflammatory,
      immunomodulatory and anti-angiogenic effects. After the approval in the United
      States of the thalidomide for treatment of erythema nodosum leprosum, several
      studies have been conducted in patients with dermatologic disorders, conditions
      associated with HIV infection, graft-versus-host disease, rheumatoid arthritis,
      Cron's disease, and cancer. In this paper the mechanisms of action of thalidomide
      and its indications in human diseases are summarized.

PMID- 11320856
TI  - [Rheumatoid arthritis. Recent findings and new pathogenic concepts].
AB  - The etiology of rheumatoid arthritis (RA) is still unknown, and many
      uncertainties regarding its pathogenetic mechanisms persist. During the past
      decade, various hypotheses have been advanced, yet none of these has been able to
      explain the complexity of the disease. In light of the most recent research, a
      sub-division of the pathogenesis of RA, in four phases, has been proposed. The
      first phase is that of tissue damage, induced by unknown infective or traumatic
      factors with the liberation of possible arthrogenic antigens that are presented
      to the immune system. In the second phase the immune and inflammatory mechanisms
      should begin to function and, if they are effective, they should determine the
      resolution of the process; the failure of these mechanisms would create a further
      amplification of the immuno-inflammation response (the third phase). The fourth
      phase would then be a chronic inflammatory with progressive articular
      destruction, as well as anatomical and functional damage. This evolution, in
      response to common pathogenic agents, is dependent upon a particular hereditary
      genetic asset (not only the HLA system) that is able to control the production of
      citokines and also upon the neuroendocrine system. The final outcome of the
      process is, therefore, determinated by multiple interference between the
      inflammatory/immune system and other systems that also interact with it (the
      integrated pathogenetic hypothesis). This hypothesis reflects the complexity of
      the immune/inflammatory system that must be considered to be an acting part of an
      integrated network of diverse systems. A better knowledge of these interactions
      needed for the discovery of potential new therapies for RA.

PMID- 11320857
TI  - [Use of erythropoietin in hematologic oncology].
AB  - Erythropoietin (EPO) is a glycoprotein synthesized by the kidney, which has a
      stimulating effect on bone marrow erythroid precursors. It has been identified
      many years ago, but its clinical use has been developed only since 1985 with the
      introduction of recombinant molecle (rHuEPO). In the past decade, rHuEPO has been
      employed in neoplastic as well as in chronic inflammatory diseases associated
      with anemia, that recognizes a multifactorial pathogenesis: defective endogenous
      EPO production, impaired erythroid proliferation due to excessive release of
      inflammatory cytokines, intrinsic abnormalities of erythroid precursors, reticulo
      endothelial blockage with reduced erythroid uptake of iron. Anemia of neoplastic
      diseases, moreover, may be induced or worsened by marrow toxicity of
      chemotherapy. The efficacy of rHuEPO in these conditions is still unclear.

PMID- 11320858
TI  - [Nitric oxide and gastroduodenal damage caused by NSAIDs. Recent findings and
      clinical implications].
AB  - A significant role of nitric oxide (NO) is being acknowledged gastroduodenal
      mucosa defense mechanism(s) against the injurious effect of NSAIDs. Many of the
      NO effects recall those of prostaglandins, such as direct protection of
      epithelial cells, mucus release, repair of mucosal erosions or ulcerations, mast
      cell degranulation. Other co-effects prove to be the inhibition of neutrophil
      adherence to the vascular endothelium, also associated with an improved mucosal
      blood flow. NO may also act by scavenging oxygen-derivedfree radicals.
      Consequently, in order to reduce the NSAID gastrotoxicity has been proposed: a)
      the linking of a NO-releasing mojety to these agents (NSAID NO-donors); b) the
      use of amtolmetin guacyl (AMG), a drug which induces an increase in the gastric
      mucosa NO concentration via direct stimulation of the local endogenous synthesis
      of this gas. Clinical studies on the efficacy and tolerability have been carried
      out with AMG versus other NSAIDs (diclofenac, indomethacin, piroxicam, naproxen)
      in patients with osteoarthritis, rheumatoid arthritis and a number of post
      traumatic arthropathies. As far as clinical symptoms are concerned AMG proves to
      be equally effective, but significantly better as far as gastroscopic lesions are
      concerned. NONSAIDs and AMG may play an important role among the long-term
      treatment of chronic inflammatory osteoarticular and rheumatic diseases.

PMID- 11320859
TI  - [Acute disseminated encephalomyelitis (ADEM)].
AB  - Acute disseminated encephalomyelitis (ADEM) is an unusual demyelinating disease
      of the CNS. We review clinical symptoms, findings from radiological and CSF
      examinations, and current treatment strategies for ADEM. This disorder is often
      associated with a precedent infection or vaccination but may also occur
      spontaneously. The clinical symptoms are highly variable. Analysis of CSF usually
      reveals lymphocytic pleocytosis and an elevated protein content but may also
      yield normal results. Magnetic resonance imaging shows solitary or multiple
      lesions within the CNS. Most patients improve quickly with methylprednisolone. If
      that fails, immunoglobulin, plasmapheresis, or cytostatic drugs can be employed.
      Unlike MS, ADEM has a monophasic course and favourable long-term prognosis.
      Multiphasic courses are very rare. There are no diagnostic criteria to
      distinguish ADEM reliably from MS during the acute phase. We presume that ADEM is
      a variant of MS and not an independent disease entity.

PMID- 11320860
TI  - [Ischemia tolerance; model for research, hope for clinical practice?].
AB  - A brief episode of ischemia renders the brain resistant against subsequent,
      longer ischemic events. This ischemic tolerance has been shown in numerous
      experimental models of cerebral ischemia. After global cerebral ischemia,
      ischemic tolerance may protect up to 90% of hippocampal CA1 neurons. In focal
      ischemia, this phenomenon reduces infarct volume by 20-60%. However, the basic
      molecular mechanisms of ischemic tolerance are largely unknown. During the
      induction phase, N-methyl-d-aspartate (NMDA) and adenosine receptors and,
      possibly, oxygen free radicals and conservation of energy metabolism are
      required. Protein kinases, transcription factors, and immediate early genes
      appear to transduce the signal into a tolerant response. Ischemic tolerance can
      be observed in different phases. The early phase lasts for several hours after
      the preconditioning stimulus and adenosine receptors and ATP-dependent potassium
      channels play a role similar to that in cardiac ischemic tolerance. The delayed
      protection, retained for a maximum of 2-4 days, currently is best explained by
      genetic remodeling with expression or repression of multiple genes. Several
      candidates have been identified to date, among them heat-shock proteins,
      cytokines, and antioxidant enzymes. Several studies have shown that angina
      pectoris before myocardial infarction represents a clinical correlate of
      experimental preconditioning protocols. Accordingly, evidence for a possible
      protective effect of transient ischemic attacks (TIAs) occurring before stroke
      are accumulating.

PMID- 11320861
TI  - [Botulinum toxin A for the treatment of headache disorders and pericranial pain
      syndromes].
AB  - For 20 years botulinum toxin A has been used for the treatment of a variety of
      disorders characterised by pathologically increased muscle contraction. Recently,
      treatment of tension headache, migraine, cluster headache, and myofascial pain
      syndromes of neck, shoulder girdle, and back with botulinum toxin A has become a
      rapidly expanding new field of research. Several modes of action are discussed
      for these indications. The blockade of cholinergic innervation reduces muscular
      hyperactivity for 3 to 6 months. Degenerative changes in the musculoskeletal
      system of the head and neck are prevented. Nociceptive afferences and blood
      vessels of the pericranial muscles are decompressed and muscular trigger points
      and tender points are resolved. The normalisation of muscle spindle activity
      leads to a normalisation of muscle tone and central control mechanisms of muscle
      activity. Oromandibular dysfunction is eliminated and muscular stress removed.
      However, the effect of botulinum toxin A cannot be explained by muscular actions
      only. Its retrograde uptake into the central nervous system modulates the
      expression of substance P and enkephalins in the spinal cord and nucleus raphe.
      Recent findings suggest an inhibition of sterile inflammation which may lead to a
      blockade of the neurogenic inflammation believed to be the pathophysiological
      substrate of primary headache disorders. The efficacy of botulinum toxin A in the
      treatment of pain disorders is being investigated in several studies at the
      moment. The results and experiences obtained so far present new alternatives in
      the treatment of chronic pain disorders. The practical use of botulinum toxin A
      is demonstrated.

PMID- 11320862
TI  - [Cognitive impairments due to add-on therapy with topiramate].
AB  - In an open study, 37 epilepsy patients were investigated with regard to cognitive
      impairments in anticonvulsant add-on therapy with topiramate (TPM). In addition
      to a preexisting antiepileptic medication, TPM administration was started and
      increased by 25 mg/week. Cognitive side effects noted by the patient or doctor
      were assessed by a neuropsychological test battery. In 18/37 patients (49%),
      cognitive deficits consisting of impaired concentration, psychomotoric slowing,
      memory deficits, and dysphasia were observed. The adverse effects became apparent
      at dosages of 50-575 mg TPM/day (average 210 mg). In four patients, they were
      reversible after reducing the dose of TPM by 25-150 mg/day. In eight patients,
      the adverse effects led to withdrawal of TPM. In spite of slow titration, the
      present study showed a higher frequency of cognitive side effects under TPM than
      was previously reported. In some patients, these side effects led to substantial
      impairments in daily life and at work. For early recognition of cognitive
      impairments, neuropsychological baseline and follow-up investigations of verbal
      fluency, psychomotor processing speed, and verbal memory are recommended.

PMID- 11320863
TI  - [Camptocormia--segmental dystonia. Proposal of a new definition for an old
      disease].
AB  - Camptocormia is defined as a forced posture with a forward-bent trunk which
      appears during standing and sitting. It was first described in 1818 by Brodie. In
      the last 100 years, numerous cases were observed. A psychogenic origin was
      presumed in most cases. We describe four patients with typical symptoms of
      camptocormia who present with the clinical and electromyographical criteria of a
      segmental dystonia. A new classification of camptocormia is proposed including
      (1) the primary form, a segmental dystonia of the abdominal wall muscles and (2)
      secondary forms. Among other conditions (psychogenic disorder, neurosis,
      myopathy, myositis, Parkinson's disease, multiple-system atrophy, thoracolumbar
      kyphosis, paraneoplastic syndrome), camptocormia is to be considered in essential
      tremor. A combination of dystonia of the abdominal wall muscles and essential
      tremor seems possible.

PMID- 11320864
TI  - [Interferon beta-1b (Betaferon)therapy in patients with relapsing-remitting
      multiple sclerosis: findings of a prospective, multi-center study of disease
      progression].
AB  - In a survey of disease course, the efficacy and tolerability of 24-month
      interferon beta-1b therapy for relapsing remitting multiple sclerosis (RRMS) were
      evaluated in 410 patients. The investigation aimed at obtaining data from general
      practice and of possibly unknown, unexpected adverse reactions. In the 241
      patients still on therapy, efficacy was rated after 24 months as "good" or "very
      good" in 75% of cases. After 24 months, 36.9% of the patients had no exacerbation
      (baseline 0.3%). Annual exacerbation rates dropped from 1.5 before treatment to
      0.7 in the second treatment year. In the 2 years before treatment, 66.2% had
      worsened by at least 0.5 points on the extended disability status scale (EDSS).
      This proportion was reduced to 41.2% after 2 years of treatment. The safety
      profile corresponded to results from controlled trials. This postmarketing survey
      supports data from the published controlled interferon beta-1b studies and
      confirms the main effects of this therapy under routine conditions in general
      practice.

PMID- 11320865
TI  - [Survival with artificial respiration at home. An open, prospective study on home
      ventilation for neuromuscular diseases, in particular, the situation of ALS
      patients].
AB  - A growing number of patients with neuromuscular disease have been treated with
      home mechanical ventilation during the past 15 years. We prospectively examined
      the long-term effects and complications of this method, particularly with regard
      to noninvasive positive pressure ventilation (NPPV). Thirty-one patients with
      amyotrophic lateral sclerosis (ALS, n = 20) or other slowly progressive
      neuromuscular diseases (NMD, n = 11) were observed for 17,517 home ventilation
      days (almost 48 ventilation years). The mean observed ventilation time was 565
      days (min/max: 30/2930). Twenty-five patients were ventilated noninvasively with
      different masks. The calculated mean survival with NPPV ventilation (criteria:
      death, tracheostomy, or patient deciding to break off) was 2052 (SE: +/- 317.8)
      days in the NMD group, 248 days (+/- 35.7) for ALS patients without bulbar
      symptoms, and 82 days (+/- 27.4) with bulbar paralysis. Complications with the
      need for intervention were observed six times more frequently with ALS than with
      NMD. NPPV is effective for years in patients with slowly progressing NMD. Those
      ALS patients without bulbar symptoms can profit for up to a year from NPPV, while
      those with bulbar paralysis can have some symptom relief. Complications of every
      kind are much more frequent in ALS patients.

PMID- 11320866
TI  - [Reduction of pain and muscle spasms by botulinum toxin A].
AB  - Botulinum toxin A (BoNT-A) develops its muscle-relaxing effect by the inhibition
      of acetylcholine (ACh) release. This toxin is also known to relieve muscular pain
      in different disorders. Conspicuously, pain in some patients responds earlier and
      sometimes even better than muscle tension, indicating that the effect of BoNT-A
      on pain is not only due to inhibition of ACh release. A questionnaire was
      distributed to 88 patients suffering from cervical dystonia (CD). Thirty-five
      completed questionnaires could be used for data analysis. After intramuscular
      injections of BoNT-A, patients with CD experience significant reductions in pain
      which sometimes occur significantly earlier than the improvements in head
      posture. In the iris sphincter muscle of the rabbit and in dorsal root ganglion
      cells (DRG) of the rat, inhibition of the release of substance P by BoNT-A has
      been shown experimentally, and BoNT-C has been proven to develop endopeptidase
      activity toward substance P (SP) in vitro. Findings in the current literature and
      our observations allow the conclusion that alleviation of muscle pain by BoNT-A
      may also be due to an effect on the release of nociceptive neuropeptides, among
      which SP seems to have a key function.

PMID- 11320867
TI  - [Delayed appearance of posttraumatic cerebrospinal fluid fistulas as a cause of
      recurrent meningitis].
AB  - Immediate post-traumatic fistulas with rhinorrhea are well known after head
      injury with frontobasal trauma. Less attention is paid to the possibility of
      delayed onset of rhinorrhea after severe head injury. Unrecognised frontobasal
      injury may cause recurrent meningitis due to communication of CSF with the
      outside world. In the last 5 years, seven patients who developed rhinorrhea 2-25
      years after trauma were treated in our department. All patients had been through
      at least two episodes of meningitis. Intermittent rhinorrhea was reported by
      four. In all cases, coronal bone window CT scan disclosed a bony defect of the
      anterior skull base, and in three cases an encephalocele was revealed on MRI.
      Treatment consisted of reconstruction of the anterior skull base with a pedicled
      galeal-pericranial flap via bifrontal craniotomy. Delayed traumatic CSF fistulas
      are not rare but must be considered in the differential diagnosis of recurrent
      meningitis.

PMID- 11320868
TI  - [Reversible multifocal encephalopathy in fulminant eclampsia].
AB  - Fulminant eclampsia characterised by the onset of focal neurological signs and
      convulsions is a rare complication of normal pregnancy in the third trimenon. We
      report on eight women (22-35 years old) with fulminant eclampsia who were
      admitted to our hospital due to seizures and central pareses. The patients
      presented with multifocal lesions involving grey and white matter preferentially
      of the occipital lobes, as evidenced by neuroimaging. Transcranial Doppler
      sonography revealed increased cerebral blood flow velocities. Treatment consisted
      of antihypertensive and anticonvulsive medication and operative termination of
      pregnancy. The patients normalised within 14 days. Our data show that fulminant
      eclampsia can induce a severe multifocal encephalopathy that can be reversible
      when treatment and termination of pregnancy are initiated immediately.

PMID- 11320869
TI  - [Evaluation of stroke units as medical technology].

PMID- 11320870
TI  - [New insights into brain function by combination of transcranial magnetic
      stimulation and functional brain mapping].
AB  - The present paper aims to summarize potential applications of transcranial
      magnetic stimulation (TMS) combined with functional brain imaging. Transcranial
      magnetic stimulation is a well-established noninvasive tool for stimulating
      circumscribed areas of the human cortex. Functional imaging techniques such as
      positron emission tomography, functional magnetic resonance imaging, and
      electroencephalographic mapping enable assessment of TMS-related functional brain
      activation. A combination of TMS and functional imaging can be useful in three
      principal ways. (1) Brain imaging before TMS is helpful in defining the accurate
      coil position over a distinct cortical area which is targeted by TMS. Since TMS
      can be used to interfere with regional cortical function during a given task, the
      effects of focal TMS on task performance can help to clarify the task-specific
      functional contribution of a given cortical area which has previously shown task
      related activation in a functional imaging study. (2) Imaging the brain during
      TMS is a promising approach for assessing cortical excitability and intracerebral
      functional connectivity. (3) By evaluating lasting effects of TMS, brain imaging
      after TMS can be employed to study the plasticity of the human cortex. Moreover,
      this approach will help to advance our understanding of therapeutical effects
      related to TMS.

PMID- 11320871
TI  - [German Society for Psychiatry, Psychotherapy and Neurology: national planning of
      hospitals should be the driving force in promoting destigmatization of community
      psychiatry].

PMID- 11320872
TI  - [Psychoacoustic scaling of acoustic voice parameters by multicenter voice
      ratings].
AB  - BACKGROUND: The purpose of the study was to analyze if perceptual voice quality
      ratings of the well-known RBH rating procedure (a 4-point scale of roughness,
      breathiness, and hoarseness) covary with acoustical voice parameters. METHODS:
      120 voice samples from subjects with healthy and hoarse voices were rated on the
      RBH-index in a multicenter study with 31 raters. Multivariate regression tree
      analysis classified the perceptual ratings as "gold standard". Voice samples were
      acoustically analyzed with a feature extraction method. Feedforward-networks were
      trained to selected acoustical parameters having highest "relative importance" in
      the regression trees. Based on the best classifier, a computer program consisting
      of 50 simultaneous working networks was developed. RESULTS: Mean probabilities
      for correct classifications were found at 0.65-0.85, implying a significance
      level over chance (0.25). Classifications of the program matched in 40% with a
      priori values in the categories roughness combined with breathiness, and in 65%
      in at least one domain. CONCLUSIONS: The new method described here provides a
      psychoacoustically based "objective" classification of hoarse voices, which seems
      to enable future analysis of new parameters (like GNE), which may even improve
      the present results.

PMID- 11320873
TI  - [Cochlear implantation: relationship between speech development and insertion
      depth in children].
AB  - BACKGROUND: The goal in pediatric cochlear implantation is improved hearing
      leading to better speech development, which may allow their integration into
      mainstream schools. Whether the intracochlear position of the electrode array has
      an influence on speech development or not is controversially discussed. PATIENTS:
      Between 1996 and 1998 29 children ranging from 1.5 to 11.8 years (median 4 years)
      were provided with a Nucleus 22M or 24M cochlear implant system. Speech and
      language skills were assessed by a closed-set test (Mainzer test) and by the
      Schmid-Giovannini score for hearing development pre-implantation and at 6, 12, 18
      and 24 months post-implantation. The position of the electrode array was
      determined by the surgical record and by a postoperative transorbital x-ray.
      Since the promontory has a thickness of one to two electrode bands, we defined
      deep insertion as more than 24 bands intracochlear. RESULTS: The patients were
      divided into 2 groups according to the insertion depth: Group 1 (n = 8) 24 bands
      (22 electrodes and 2 stiffening rings correspond to < or = 18 mm) or less and
      group 2 (n = 21) more than 24 bands intracochlear correspond to > 18 mm). The
      mean closed-set test scores 12 months post-implantation were 51.4% and 68.5% for
      group 1 and group 2, respectively. Schmid-Giovannini test scores were 8.7 for
      group 1 and 10.1 for group 2. There was no significant statistical difference in
      the closed-set and Schmid-Giovannini test scores. We observed incomplete
      insertion (i.e. less than 22 active bands are intracochlear) because of electrode
      extrusion in only one child. CONCLUSION: Speech development in children does not
      improve with deeper insertion of the cochlear implant electrode array.

PMID- 11320874
TI  - [Cochlear hearing loss following Mycoplasma pneumoniae infection].
AB  - BACKGROUND: A sudden unilateral hearing loss in childhood is commonly regarded as
      an unusual event. CASE-REPORT: In this paper, we report of a 10 year old girl
      suffering from a unilateral right-sided sudden hearing loss following an acute
      infection with Mycoplasma pneumoniae, which is also rarely observed. Maximum
      hearing loss was estimated around 30 dB (0.25-6 kHz), which resolved after
      infusions using plasma expanders. Both transitory and distortion product
      otoacoustic emissions remained absent, while latencies of acoustically evoked
      potentials were normal. DISCUSSION: This suggests a damage of outer hair cell
      function as an explanation for the observed hearing loss. The coincidence of two
      rare events for children such as a spontaneous sudden unilateral hearing loss
      combined with an infection with Mycoplasma pneumoniae gives rise to the
      hypothesis of a causal relationship that is discussed according to the
      literature.

PMID- 11320875
TI  - [Retraction of the endolymphatic membranes in temporal bones of the Wittmaack and
      Tufts collections].
AB  - BACKGROUND: In histologic studies, the volumetric status of the intralabyrinthine
      fluids is judged by the position of the endolymphatic membranes. Bulging of the
      membranes, commonly known as endolymphatic hydrops, is assumed to be caused by
      excess of endolymph. The opposite situation, retraction of the membranes is,
      however, only incidentally described and relatively little attention has been
      paid to its significance. Almost one hundred years ago Wittmaack described
      retraction of the endolymphatic membranes, which has since been considered to be
      preparation artifact--a concept that essentially remains unchallenged. To test
      the validity of this long premise, we examined two sets of temporal bones from
      different centers. MATERIAL AND METHODS: We studied the following collections: 1.
      The Wittmaack collection in Hamburg, Germany. The original material of 67
      temporal bones (patient ages 0-92 years, average age 35.2 years) on which
      Wittmaack based his opinions. 2. For comparison and to exclude age related
      phenomena, 125 temporal bones from 73 children between the ages newborn to ten
      years (average age 13.4 months, median 1.5 months) from the temporal bone
      collection of the Department of Otolaryngology Tufts University School of
      Medicine. All specimens were studied by light microscopy. Retraction was defined
      as depression of Reissner's membrane toward the stria vascularis and the Organ of
      Corti in more than one cochlear turn and was graded into mild, moderate and
      severe. Additionally the saccule, utricle and semicircular ducts were examined
      for collapse. RESULTS: The reevaluation of the 67 temporal bones described by
      Wittmaack, including those of 7 children below the age of 10 years, showed
      retraction of Reissner's membrane in 81% compared to 33% of the temporal bones
      from the Tufts collection. In contrast to the high incidence of retraction in the
      cochlear duct, fewer saccules (12%) and utricles (4%) were collapsed in the Tufts
      collection. In the Wittmaack collection no significant differences between the
      underlying diseases were found, however in the Tufts collection the group of
      children who suffered from extracochlear infections and malignancies had a higher
      frequency of retraction. CONCLUSION: Mild retraction might be to some extent
      physiologic or even artifactual. Severe retraction, however, is a definitive
      finding that is a part of a local or regional otopathologic process. Of material,
      it is quite possible that Wittmaack's original observations of what he called
      "hypotonic collapse" was of viral origin (viruses were not known during
      Wittmaack's time), ototoxicity or even of genetic origin.

PMID- 11320877
TI  - [Injuries in the throat-nose-ear area by automobile air bags].
AB  - BACKGROUND: Airbags are successful in avoiding or in reducing serious injuries
      caused by motor vehicle accidents. On the other hand airbag deployment has led to
      a new kind of injuries. Only a few publications about that item exist. The
      experiences made with two patients after airbag deployment are described. The
      relevant literature is discussed. PATIENTS: Two patients after airbag injuries
      were examined. The face of the first patient hit a regularly expanding airbag.
      Afterwards his nose was obviously deformed. In the other case both front airbags
      of a car burst triggered by a frontal crash. The symptoms of this patient were
      painful itching skinlesions in his face, unilateral hearing loss and tinnitus.
      RESULTS: The first described patient had a clinical and radiological provable
      fracture of his nasal bone with a frontal impression. The facial skin of the
      other patient was etched by the filling gas of the airbags. He was also suffering
      from an acoustic trauma. These cases are compared to other cases found in the
      literature. CONCLUSIONS: Oto-rhino-laryngological injuries can be caused by
      airbag deployment, especially by bursting airbags. Beside of outward injuries
      like dermatological hurts and fractures of the facial skeleton also more serious
      and life-threatening traumata can occur with damage of the cervical spine and
      upper airway. Moreover otologic handicaps like temporary or permanent hearing
      loss, tinnitus, vertigo, otalgia and tympanic membrane perforations are possible
      consequences.

PMID- 11320876
TI  - [Unilateral opacification of the paranasal sinuses in CT or MRI: an indication of
      an uncommon histological finding].
AB  - BACKGROUND: Clinical and radiological differentiation between subacute or chronic
      sinusitis and differential pathologies such as malignoma, inverted papilloma or
      mycosis can be very difficult. In some cases the CT- or MRI-scan shows a
      unilateral opacification of the paranasal sinuses. Which histological results can
      be found in patients with persisting sinusitis related problems and a unilateral
      opacification of the paranasal sinuses in the CT- or MRI-scan? There are only a
      few publications on this topic. PATIENTS: In a prospective study between June
      1998 and November 1999 all patients who underwent surgery in our Department for
      subacute or chronic sinusitis problems were included into our study group if they
      had a unilateral opacification of the paranasal sinuses. Thereafter, the same
      neuroradiologist verified the unilateral radiological findings on CT or MRI,
      unaware of the clinical and histological findings. Cases with a pre-existing
      histological examination, previous operation or injury to the paranasal system
      were excluded from this study. Data on clinical symptoms, radiological and
      histological findings were analysed. RESULTS: 43 cases with unilateral opacified
      paranasal sinuses were diagnosed by means of CT or MRI. These were comprised of
      24 males and 19 females with an average age of 43.6 years (range 6 to 88 years).
      The major findings of our study were as follows: Firstly unilateral opacification
      of the paranasal sinuses is often (19/43 cases or 43%) associated with diseases
      othe than simple chronic sinusitis (8 inverted papilloma, 5 malignoma, 3 mycoses
      and one brown tumor, one osteoidosteoma and one haemangioma). Secondly the
      incidence of significant pathology other than simple chronic sinusitis rises
      strikingly with increasing age of the patient. For instance pathologies other
      than simple chronic sinusitis were found in 14% (1/7) of cases in the under 16
      years group, 27% (6/22) of cases in the 16-60 years group and in 86% (10/12) of
      cases in the over 60 years group. Concerning clinical signs of our patients with
      unilateral sinus opacity 7 of 11 patients (63%) with epistaxis and 3/5 with
      diplopia had histological findings other than simple chronic sinusitis. In
      contrast unilateral rhinorrhea, unilateral nasal congestion and cephalgia were
      not of predictive value. CONCLUSION: Unilateral opacification of paranasal
      sinuses in the CT or MRI is--especially at a higher age--an indice for a neoplasm
      or mycotic sinusitis and therefore an early histological diagnosis or operative
      treatment is always suggested.

PMID- 11320878
TI  - [The ulnar artery or the radial artery can be used alternatively in the free
      underarm flap].
AB  - BACKGROUND: The free, microvascular forearm flap is harvested and transplanted
      with the radial artery most frequently. Lovie and coworkers published the
      possibility to elevate this flap with the ulnar artery in 1984. Later on we
      introduced a DOPPLER-sonographic method to determine the artery which is dominant
      for the perfusion of the hand in order to leave this artery in the forearm. This
      procedure might minimize the donor site morbidity. METHOD: In 9 years we treated
      30 consecutive patients this way and interviewed them for dysaesthesia in contact
      with coldness. Furthermore we performed a standardized exposition to 17 degrees C
      cold water. RESULTS: In 4 of 30 forearm flaps we had to experience flap necrosis.
      One patient suffered from dysaesthesia during extreme exposure to coldness
      (motorcycling during the winter without gloves). None of the patients showed
      dysaesthesia after one minute of cold water exposure. DISCUSSION: Flap necrosis
      was relatively frequent in our patients but not related to the feeding vessel. On
      the other hand perfusion related donor site morbidity was extremely rare. To use
      the radial or the ulnar artery alternatively as the feeding vessel for
      transplantation of the forearm flap seems to be reasonable and keeps feared
      complications (disturbance of perfusion, cold-intolerance) rare.

PMID- 11320879
TI  - [Long-term results of radium contact irradiation of laryngeal carcinoma and their
      relevance in modern therapeutical regimens].
AB  - BACKGROUND: Despite the fact that it is widely accepted that a second radiogenic
      carcinoma might occur after radiotherapy of laryngeal carcinomas, there are only
      a few long-term follow-up studies published yet. METHODS: Between 1973 and 1988
      193 patients have been treated by radium contact irradiation because of glottic
      cancer (Tcis, T1, T2). After the cancer had been diagnosed by biopsy, a partial
      resection of the thyroid cartilage in the shape of a window 16 x 18 mm was
      carried out and a self-retaining capsule which harbours the radium was brought
      into position. RESULTS: 190 (181 men and 9 women) out of 193 patients could be
      followed up. At the time of investigation 109 patients had already died, 66
      intercurrently. The actuarial disease free survival rate 5 and 10 years for
      Tcis/T1 glottic cancers were 84.6% and 83.6%. For T2 carcinomas a rate of 100%
      was found respectively. The actuarial overall survival rate was 96.8% after 5 and
      93.1% after 10 years for Tcis/T1 carcinomas. The T2 carcinomas revealed an
      actuarial overall survival rate of 100% after 5 and 10 years. CONCLUSIONS: As the
      results of radium contact irradiation are not better than those which can be
      achieved by microsurgery or modern irradiation techniques no indication exists
      for a radium contact irradiation of glottic laryngeal cancer today.

PMID- 11320880
TI  - [Clinical manifestation of Ewing's sarcoma as a retrotonsillar pharyngeal tumor].
AB  - BACKGROUND: Ewing's sarcoma is a malignant tumour which usually arises from bony
      structures. It can be found in dia- or metaphysis of bones of the extremities but
      as well in 50% of cases in skeletal parts of the trunk. Clinically patients often
      present with various symptoms as there are pain, swelling and progredient loss of
      function if extremities are involved. But in many cases, Ewing's sarcoma shows a
      lack of specific symptoms and therefore stays inapparent for a long time. CASE
      REPORT: A 14-year-old patient complained about intermittent nuchal pain and was
      sent to hospital because of an extensive retropharyngeal swelling. The
      preoperative imaging showed a tumour of the soft tissue of the neck. It had
      reached the cervical spine and after surgical treatment it was histologically and
      molecular biologically diagnosed as a Ewing's sarcoma arising from the
      transversal processes of the atlas. CONCLUSION: Since Ewing's sarcoma may have an
      immense component of soft tissue it has to be included in the range of
      differential diagnosis of soft tissue tumours of the head and neck, e.g., as
      there are extracranial schwannoma, inflammatory lymph nodes or lymph node
      metastases and lateral and medial cysts of the neck.

PMID- 11320881
TI  - [The interesting case No. 43].

PMID- 11320882
TI  - [Surgery of the mediastinum. II].

PMID- 11320883
TI  - [What is your diagnosis? Verrucae plantares (plantar warts)].

PMID- 11320885
TI  - [Prevention of pelvic recurrence by preoperative radiochemotherapy and total
      mesorectal excision of rectal carcinoma?].
AB  - Preoperative radiotherapy (RT) alone or in combination with a pre- or
      postoperative chemotherapy reduces the recurrence rate and increases the survival
      rate for patients with resectable rectal cancer. The therapeutic index, i.e.
      relationship between effects and side effects is objective of studies. Especially
      toxicities to the small intestine and to the sphincter function are evaluated.
      Preoperative radiotherapy achieves the best results. The treatment volume
      includes the mesorectum in case of continence maintaining surgery and includes
      the anal sphincter in case of abdominoperineal resection. To exclude the small
      intestine from the RT-field, we prefer the use of 3 or 4 field technique in a
      prone position with filled bladder, using an optimal field limitation. The
      Swedish study, which uses 25 Gy in five fractions per week leads to an increased
      rate of acute and late toxicities. A fractionation schedule using 45-50 Gy in
      five weeks should be preferred. During the radiotherapy the patient is followed
      up once per week. If surgery is foreseen, it should take place as soon as 3 weeks
      after the end of radiotherapy. If a primary surgery is performed preoperatively,
      the operative finding should be discussed with the surgeon. Quality control
      programs have to certify optimal treatment of the patient by radiotherapist and
      surgeon.

PMID- 11320884
TI  - [Rectal carcinoma--oncologically adequate resection].
AB  - The local recurrence rate is besides distant metastatic spread the most relevant
      factor for the longterm survival of patients with rectal cancer. Of decisive
      importance are the experienced surgeon and special techniques such as the precise
      mesorectal dissection with respect of the holy planes. Total mesorectal excision
      (TME) for carcinomas of the lower and middle third of the rectum and a sufficient
      distal margin of 2 cm reduced the local recurrence rate to below 10% and allow
      sphincter preservation in more than 80%. The local excision is ideal for low-risk
      patients with circumscript T1-tumors. In high-risk-patients the operation should
      be followed by additional chemoradiation therapy. Multivisceral surgery and
      pelvic exenteration do have a place in patients with locally advanced tumors,
      which should be treated by neoadjuvant radiochemotherapy. Laparoscopic operations
      of rectal cancer show first promising results but should, however, be restricted
      to controlled clinical trials.

PMID- 11320886
TI  - [Radiochemotherapy plus hyperthermia in rectal carcinoma].
AB  - In locally advanced rectal cancer (uT3/uT4) resectability as well as local
      control is reduced. In the patients combined preoperative radiochemotherapy
      demonstrated an increase of resectability and a reduction of local recurrence.
      Radiotherapy was applied in standard blocks, 5 x 1.8 Gy up to 45 Gy. Chemotherapy
      consisted out of two cycles of 5-Fluorouracil (300-350 mg/m2/d) and Leucovorin
      (50 mg). Prior to radiotherapy additionally thermotherapy was carried out using
      the SIGMA 60 applicator BSD 2000 once a week. The hyperthermia method is based on
      heating up affected tissue compartments to temperature above 42 degrees Celsius
      without damaging surrounding tissue compartments. In regional hyperthermia tumors
      in the abdominal region are treated by emitting radio waves into the patient. 4-6
      weeks after radiochemotherapy, surgery was performed. The therapeutic toxicity
      was acceptable and the resectability rate was up to 90%. Response rate to
      treatment was 60%. Our data with preoperative combined treatment in locally
      advanced rectal cancer revealed encouraging downstaging, local control, and
      survival rates.

PMID- 11320887
TI  - [Bacteriuria in a 47-year-old long-term catheterized patient].

PMID- 11320888
TI  - Ricinosomes: an organelle for developmentally regulated programmed cell death in
      senescing plant tissues.
AB  - This review describes aspects of programmed cell death (PCD). Present research
      maps the enzymes involved and explores the signal transduction pathways involved
      in their synthesis. A special organelle (the ricinosome) has been discovered in
      the senescing endosperm of germinating castor beans (Ricinus communis) that
      develops at the beginning of PCD and delivers large amounts of a papain-type
      cysteine endopeptidase (CysEP) in the final stages of cellular disintegration.
      Castor beans store oil and proteins in a living endosperm surrounding the
      cotyledons. These stores are mobilized during germination and transferred into
      the cotyledons. PCD is initiated after this transfer is complete. The CysEP is
      synthesized in the lumen of the endoplasmic reticulum (ER) where it is retained
      by its C-terminal KDEL peptide as a rather inactive pro-enzyme. Large number of
      ricinosomes bud from the ER at the same time as the nuclear DNA is
      characteristically fragmented during PCD. The mitochondria, glyoxysomes and
      ribosomes are degraded in autophagic vacuoles, while the endopeptidase is
      activated by removal of the propeptide and the KDEL tail and enters the cytosol.
      The endosperm dries and detaches from the cotyledons. A homologous KDEL-tailed
      cysteine endopeptidase has been found in several senescing tissues; it has been
      localized in ricinosomes of withering day-lily petals and dying seed coats. Three
      genes for a KDEL-tailed cysteine endopeptidase have been identified in
      Arabidopsis. One is expressed in senescing ovules, the second in the vascular
      vessels and the third in maturing siliques. These genes open the way to exploring
      PCD in plants.

PMID- 11320889
TI  - Atomic-size metallic conductors.
AB  - A number of newly developed experimental techniques and theoretical insights have
      made it possible to investigate the electronic transport properties of conductors
      at the atomic scale. Although the field is still rapidly evolving, a number of
      new discoveries, concepts and insights have been clearly established. The central
      theme of this brief review will be the electronic conductance of a single atom.
      This conductance can be described in terms of a number of quantum modes, where
      the number of these modes is determined by the valence orbitals of the metal
      atom. I first present some elements of the theoretical basis for these concepts,
      and discuss the various experimental tools that have been used to verify it.
      Electronic conductance at the atomic scale cannot be separated from the problem
      of the energetics and dynamics of atomic-scale configurations. Investigations in
      this area have produced a number of surprising discoveries, and of these I will
      discuss the spontaneous formation of a conducting chain of single gold atoms, and
      the enhanced stability of nanowires of alkali metals at 'magic' radii determined
      by shell structure of the conductance modes.

PMID- 11320890
TI  - Microstructural homogeneity of support silk spun by Eriophora fuliginea (C.L.
      Koch) determined by scanning X-ray microdiffraction.
AB  - Scanning X-ray microdiffraction (SXD) permits the 'imaging' in-situ of
      crystalline phases, crystallinity and texture in whole biopolymer samples on the
      micrometre scale. SXD complements transmission electron microscopy (TEM)
      techniques, which reach sub-nanometre lateral resolution but require thin
      sections and a vacuum environment. This is demonstrated using a support thread
      from a web spun by the orb-weaving spider Eriophora fuliginea (C.L. Koch).
      Scanning electron microscopy (SEM) shows a central thread composed of two fibres
      to which thinner fibres are loosely attached. SXD of a piece of support thread
      approximately 60 microns long shows in addition the presence of nanometre-sized
      crystallites with the beta-poly(L-alanine) structure in all fibres. The
      crystallinity of the thin fibres appears to be higher than that of the central
      thread, which probably reflects a higher polyalanine content of the fibroins. The
      molecular axis of the polymer chains in the central thread is orientated parallel
      to the macroscopic fibre axis, but in the thin fibres the molecular axis is
      tilted by about 71 degrees to the macroscopic fibre axis. A helical model is
      tentatively proposed to describe this morphology. The central thread has a
      homogeneous distribution of crystallinity along the macroscopic fibre axis.

PMID- 11320891
TI  - Colony disassociation following diet partitioning in a unicolonial ant.
AB  - Discriminating nestmates from alien conspecifics via chemical cues is recognized
      as a critical element in maintaining the integrity of insect societies. We
      determined, in laboratory experiments, that nestmate recognition in an introduced
      population of the Argentine ant, Linepithema humile, is modified by hydrocarbons
      acquired from insect prey, and that workers from spatially isolated colony
      fragments, each provided with prey that possessed distinct cuticular
      hydrocarbons, displayed aggressive behavior towards their former nestmates.
      Isolation for 28 days or more between colony fragments fed different prey was
      sufficient to prevent re-establishment of inter-nest communication for at least
      an additional 28 days through the introduction of a bridge between the nests.
      Ants possessed intrinsic cuticular hydrocarbons plus only those hydrocarbons from
      the prey they received during the isolation period. Colony fragments which were
      isolated for less than 28 days reunited with workers possessing both prey
      hydrocarbons. Therefore, L. humile nestmate recognition may be dynamic, being in
      part dependent on the spatio-temporal distribution of prey, along with physical
      factors permitting or restricting access of subcolony units to those prey.

PMID- 11320892
TI  - Structural differences in the drone olfactory system of two phylogenetically
      distant Apis species, A. florea and A. mellifera.
AB  - Male insects that are attracted by sex pheromones to find their female mates over
      long distances have specialized olfactory subsystems. Morphologically, these
      subsystems are characterized by a large number of receptor neurons sensitive to
      components of the female's pheromones and hypertrophied glomerular subunits
      ('macroglomeruli' or 'macroglomerular complexes') in the antennal lobes, in which
      the axons of the receptor neurons converge. The olfactory subsystems are adapted
      for an increased sensitivity to perceive minute amounts of pheromones. In Apis
      mellifera, drones have 18,600 olfactory poreplate sensilla per antenna, each
      equipped with receptor neurons sensitive to the queen's sex pheromone, and four
      voluminous macroglomeruli (MG1-MG4) in the antennal lobes. In contrast, we show
      that drones of the phylogenetically distant species, Apis florea, have only 1,200
      poreplate sensilla per antenna and only two macroglomeruli in their antennal
      lobes. These macroglomeruli are homologous in anatomical position to the two most
      prominent macroglomeruli in A. mellifera, the MG1 and MG2, but they are much
      smaller in size. The morphological and anatomical differences described here
      suggest major modifications in the sex-pheromone processing subsystem of both
      species: (1) less pheromone sensitivity in A. florea and (2) a more complex sex
      pheromone processing and thus a more complex sex-pheromone communication in A.
      mellifera. Research in honey bee sex-pheromone communication dates back to the
      1960s, when Gary (1962) demonstrated that in Apis mellifera the queen's
      mandibular gland secretion and especially its main component, 9-ODA (9-keto-2(E)
      decenoic acid), is highly attractive to drones on their nuptial flight. Later,
      cross-species attraction experiments showed that other honey bee species, Apis
      florea, A. cerana, and A. dorsata probably also use the queen's mandibular gland
      secretion as a mating attractant (Butler et al. 1967; Sanasi et al. 1971).
      Besides its function in mating behavior, the queen's mandibular gland secretion
      is the main pheromone regulating queen-worker interactions (Free 1987). In this
      context, several studies have demonstrated the behavioral significance of single
      components (Slessor et al. 1988) and differences in the composition of the
      secretion between Apis species (Plettner et al. 1996, 1997; Keeling et al. 2000).
      Regarding the interspecific differences in the queen's signal, the question
      arises whether this variation is reflected in the olfactory system of drones and
      workers of the various species.

PMID- 11320893
TI  - The first discovery of a brachiosaurid from the Asian continent.
AB  - Described here is a sauropod tooth from the Early Cretaceous of South Korea,
      similar to Brachiosaurus. The crown of the tooth is beveled off lingually so that
      when worn it presents a chisel-like edge. This find confirms the presence of a
      brachiosaurid in East Asia during the Early Cretaceous.

PMID- 11320894
TI  - Are queen Bombus terrestris giant workers or are workers dwarf queens? Solving
      the 'chicken and egg' problem in a bumblebee species.
AB  - In the social bee, Bombus terrestris, the two castes differ in size and
      physiology, but not in any other morphological and anatomical aspects. The size
      differences between the castes are the result of longer instar duration in
      prospective queen larvae. It appears that queen larvae are programmed to have a
      higher molting weight at the end of the 2nd, 3rd and 4th instars. Calculation of
      the growth ratio, the ratio between the logarithm of molting weight at two
      successive instars, revealed that queen larvae have a linear growth ratio over
      the entire larval development as predicted by Dyar's rule. In the worker larvae,
      in contrast, linearity of the growth ratio breaks after the second instar,
      resulting in larval molting at lower weights than expected by Dyar's rule. We
      therefore suggest that workers' development is abnormally shortened, either by
      parental manipulation or by adopting a different growth plan in response to the
      queen's signal.

PMID- 11320895
TI  - Synthetic attractants for the bark beetle parasitoid Coeloides bostrichorum
      Giraud (Hymenoptera: Braconidae).
AB  - Coeloides bostrichorum Giraud parasitoids (Hymenoptera: Braconidae) attack late
      larval stages of various bark beetle species breeding in spruce. Volatile
      compounds collected from Norway spruce (Picea abies) infested by Ips typographus
      L. (Coleoptera: Scolytidae) were analysed by coupled gas chromatography-mass
      spectrometry (GC-MS) and GC-electroantennographic detection (GC-EAD). Monoterpene
      hydrocarbons are the predominant volatile compounds of fresh Norway spruce, while
      the presence of oxygenated monoterpenes indicates damaged trees. Between one and
      eight EAD-active oxygenated monoterpenes were used, in amounts reflecting their
      natural abundance in spruce trees containing bark beetle larvae, to prepare five
      synthetic baits which were tested in wind tunnel bioassays. Odour samples
      collected from spruce logs containing the preferred host stage were attractive,
      while similar samples from uninfested logs failed to elicit any flight activity.
      However, when a four- or an eight-component synthetic bait was added to volatiles
      collected from uninfested spruce logs, this combination was as attractive as
      volatiles collected from infested spruce logs.

PMID- 11320896
TI  - Allogeneic transplantation of blood stem cells: coming of age?
AB  - Mobilized peripheral blood progenitor cells (PBSC) are increasingly being used
      instead of bone marrow for allogeneic transplantation. The purpose of the present
      article is to give a concise and clinically oriented overview on current results
      and perspectives of allogeneic peripheral blood stem cell transplantation, with
      particular focus on reconstitution of hematopoiesis and the immune system, graft
      versus-host disease, graft-versus-leukemia effects, intensity-reduced
      conditioning, and graft engineering.

PMID- 11320897
TI  - Quality of life and factors related to perceived satisfaction with quality of
      life after allogeneic bone marrow transplantation.
AB  - The quality of life after bone marrow transplantation (BMT) was studied in 109
      adult allogeneic BMT recipients transplanted on at the Helsinki University
      Central hospital for a haematological malignancy. Physical, functional, emotional
      and social well-being was measured on the Functional Assessment of Cancer Therapy
      Scale (FACT-BMT) and a shortened version of the Profile of Mood States Scale
      (POMS) and by the MOS social support survey and a Brief Measure of Social Support
      (SSQ6). The results of the present study replicate those of previous
      investigations by finding that physical well-being, educational level, age at BMT
      and social support have an impact on the perceived quality of life of BMT
      patients. Our results indicate that these factors have a varying impact at
      different time points during the post-BMT recovery process. During the first
      three years after BMT, physical well-being proved to be a highly significant (P <
      0.001) factor for perceived life satisfaction. Moreover, physical well-being
      showed an average significant improvement after the first post-BMT year. The
      percentage of the recipients experiencing the highest levels of satisfaction with
      life increased from 51% during the first year after BMT to 81% for those patients
      five years post-BMT. One year after BMT, 75.6% of the BMT recipients were able to
      work, 67.8% of the patients were actively participating in work/school and 7.8%
      were unemployed.

PMID- 11320898
TI  - Treatment of relapsing leukemia after allogeneic blood stem cell transplantation
      by using dose-reduced conditioning followed by donor blood stem cells and GM-CSF.
AB  - Ten patients with high-risk acute myeloid leukemia (AML), chronic myeloid
      leukemia (CML), and myelodysplastic syndrome (MDS) relapsing early (< 1 year, n =
      8) or late (> or = 1 year, n = 2) after allogeneic transplantation were treated
      with cytoreductive chemotherapy followed by unmanipulated peripheral blood stem
      cell transplantation (PBSCT) from related (n = 3) and unrelated donors (n = 7).
      In order to enhance the graft-versus-leukemia effect, patients received no graft
      versus-host disease (GVHD) prophylaxis and granulocyte-macrophage colony
      stimulating factor (GM-CSF) was given at a dose of 60 micrograms/m2 after
      transplant. Acute GVHD grade I-IV was seen in all patients. Eight out of ten
      patients achieved complete remission: one out of two patients with AML and late
      relapse is in good condition with limited chronic GVHD more than 1 year after the
      second PBSCT. The other patient died on day +171 after the second PBSCT from
      cerebral aspergillosis. One patient with blastic phase CML achieved molecular
      remission but died +330 days after the second PBSCT because of intracranial
      bleeding. Of the remaining five patients, three died of infectious complications
      on days +36, +70, and +27, one patient died with extramedullary relapse on day
      +35, and one from multi-organ failure in association with acute GVHD on day +32
      after the second PBSCT. Two out of ten showed progressive disease and died on
      days +30 and +90, respectively. Although several patients achieved complete
      remission, the high risk of GVHD and treatment-related mortality should be kept
      in mind, especially when a second transplant is considered during a period of
      less than 12 months after the first procedure. Monitoring of minimal residual
      disease might predict relapse thus preventing high doses of cytotoxic drugs for
      reconditioning. The potential of GM-CSF to enhance the graft-versus-leukemia
      reactivity after cytoreductive therapy for allogeneic transplantation warrants
      further investigation.

PMID- 11320899
TI  - Effect of locally applied GM-CSF on oral mucositis after stem cell
      transplantation: a prospective placebo-controlled double-blind study.
AB  - Oral mucositis is a frequent side effect of myeloablative chemo- and radiotherapy
      preceding stem cell transplantation. It causes pain, poor food intake, and is a
      port of entry for infection. We studied whether GM-CSF applied topically in the
      oral cavity can prevent or ameliorate this mucositis. In 36 consecutive patients
      undergoing a stem cell transplantation, we performed a double-blind placebo
      controlled study of 300 micrograms GM-CSF in a 2% methylcellulose gel daily
      versus a 2% methylcellulose gel alone. Both were locally applied in the oral
      cavity. The primary end-point was mucositis as measured by the WHO toxicity scale
      for mucositis, oral assessment scale, and a subjective pain scale, all scored
      daily. The secondary end-points were need to give parenteral nutrition and
      morphine, incidence of fever and infections, and duration of neutropenia and
      hospitalization. No differences were found in the median subjective pain scores,
      WHO scores, and oral assessment scores between the placebo and the GM-CSF groups.
      In both groups, nine patients required morphine for pain control. Ten patients in
      the placebo group and 11 in the GM-CSF group received parenteral nutrition.
      Documented infections, use of broad-spectrum antibiotics, and number of days with
      fever were similar in the placebo and the GM-CSF groups. The duration of
      neutropenia below 0.5 x 10(9)/l (median 14.5 days in the placebo group versus 17
      days in the GM-CSF group) and the duration of hospitalization (28.5 versus 29
      days) was also not significantly different. We found no beneficial effect of 300
      micrograms GM-CSF dissolved in a 2% methylcellulose gel applied locally for chemo
      and radiotherapy-induced mucositis in patients undergoing a stem cell
      transplantation.

PMID- 11320900
TI  - Treatment of elderly patients with intermediate- and high-grade non-Hodgkin's
      lymphoma: a retrospective population-based study.
AB  - PURPOSE AND METHODS: Nowadays more people are becoming older. The median age of a
      patient with non-Hodgkin's lymphoma (NHL) at diagnosis is over 60 years. The
      incidence of NHL in elderly has increased in the last decades. Therefore, in the
      future, NHL will be diagnosed more often in the elderly. Data of all patients in
      the south-east of the Netherlands with newly diagnosed NHL between January 1991
      and January 1995 were analysed in a retrospective multicentre population-based
      study to investigate if and how elderly patients (> 60 years) with advanced NHL
      (Ann Arbor Staging > or = IIB) of intermediate- and high-grade malignancy were
      treated. Treatment modalities applied, outcome, and causes of death were
      evaluated. Treatment was considered inadequate if it deviated from the standard
      anthracycline-containing chemotherapy (CNOP/CHOP) for a minimum of six cycles.
      RESULTS: The entry criteria were met by 68 patients. Of these patients, 57
      (83.8%) were treated and 11 (16.2%) were not treated. The treatment consisted of
      CHOP (36 patients), CNOP (6 patients), chlorambucil (13 patients), or COP (2
      patients). Forty-two of 68 patients had adequate treatment, but 14 of 42 (33.3%)
      patients had a suboptimal numbers of cycles (< 6). Of 28 patients with adequate
      chemotherapy, only 16 had the optimal number of cycles and dose; the result is
      that the treatment of 76.5% (52/68) of patients differed from that of their
      younger counterparts. The most important reason for treatment not being optimal
      was high age (23%) or poor performance (35%). In the appropriately treated
      patients, 62.5% (10/16) had a complete response. Survival in the CHOP/CNOP
      treated group was better than in other groups. The main cause of death in the
      total study group was NHL. The results cannot be explained by the different
      international prognostic index. CONCLUSION: A significant subset (76.5%) of
      elderly people with intermediate/high-grade NHL received suboptimal therapy,
      mainly because of a suboptimal performance status. However, a significant part of
      the patients (23%) were not treated optimally because of high age, despite a good
      performance. For improving the overall survival in the elderly, it is not only
      the schedule that is important, but also the intention to treat the elderly
      patient.

PMID- 11320901
TI  - Clinical and morphological criteria for the diagnosis of prefibrotic idiopathic
      (primary) myelofibrosis.
AB  - A clinicopathological study was performed to define initial-prefibrotic precursor
      stages of idiopathic (primary) myelofibrosis (IMF) by presenting laboratory and
      histological bone marrow features. Contrary to the usually accepted diagnostic
      requirements for IMF, including bone marrow fibrosis and a leukoerythroblastic
      blood picture, we found that 80 patients did not completely comply with these
      criteria. In particular, this cohort displayed no increase in the reticulin
      collagen fiber content of the bone marrow at onset. Therefore, these cases were
      occasionally regarded as unclassifiable chronic myeloproliferative disorders
      (MPDs), or presumptively as essential thrombocythemia (ET). Patients were
      characterized by a certain set of clinical parameters comprising a borderline to
      slight leukocytosis and therapy-refractory anemia, minimal to modest
      splenomegaly, and often an elevated platelet count. Peripheral blood films
      revealed, only very sparsely, tear drop cells and a few erythroid and myeloid
      precursors, but no definite leukoerythroblastic reaction. Bone marrow
      histopathology was consistent with an increase in cellularity and a prominent
      left-shifted neutrophil granulopoiesis. Erythropoiesis disclosed a slight
      reduction with small to medium-sized islets. Megakaryopoiesis was the most
      prominent diagnostic hallmark to distinguish initial-prefibrotic IMF from the
      allied subtypes of MPDs. This cell lineage was not only characterized by a
      conspicuous growth and abnormal clustering, but also by a pronounced deviation
      from nuclear-cytoplasmic differentiation (dysplastic appearance). Cytological
      anomalies were compatible with a large variety of size and shape, ranging from
      giant- to atypical micromegakaryocytes with compact and bulky, cloud-like nuclei,
      due to a coarse lobulation and a frequent occurrence of naked (denuded) nuclei.
      Follow-up examinations, including sequential trephine biopsies in 22 patients,
      revealed a transition into myelofibrosis accompanied by laboratory findings in
      keeping with manifest IMF. In conclusion, morphological and clinical parameters
      have been validated by this study, which are consistent with a set of diagnostic
      criteria to recognize initial or prefibrotic precursor stages of IMF.

PMID- 11320902
TI  - A bone marrow report of absent stainable iron is not diagnostic of iron
      deficiency.
AB  - The absence of stainable iron in a bone marrow aspirate is widely considered to
      be diagnostic of iron deficiency anemia (IDA). We re-evaluated this concept by
      studying a cohort of 108 consecutive bone marrow specimens from an unselected
      series of patients who were seen at a hematology clinic and in whom iron stores
      were reported as being absent. A review of the pathologic reports revealed 19
      inadequate specimens and 15 with decreased, but not absent, iron stores. Thus,
      only 74 of the 108 cases had been accurately reported. In 37 of these cases,
      adequate clinical and laboratory data were available and allowed further
      analysis. In 18 patients, careful review of patient history, physical
      examination, results of endoscopic procedures, and follow-up information failed
      to suggest the presence of IDA (group A). The review process in the remaining 19
      patients suggested the possibility of IDA (group B). Significant differences
      between groups A and B were observed in serum ferritin (P = 0.001) and red blood
      cell mean corpuscular volume (P = 0.004). In contrast, the two groups did not
      differ significantly in hemoglobin concentration, serum iron, total iron-binding
      capacity, transferrin saturation, or erythrocyte sedimentation rate. These
      observations suggest that a pathology report of absent bone marrow hemosiderin
      may be inaccurate in more than 30% of cases and, even when accurate, may not
      necessarily signify the presence of IDA. Measurement of the serum ferritin level
      is needed to confirm a clinical diagnosis.

PMID- 11320903
TI  - Effective treatment with rituximab in a patient with refractory prolymphocytoid
      transformed B-chronic lymphocytic leukemia and Evans syndrome.
AB  - A 65-year-old male who had been diagnosed as having chronic lymphocytic leukemia
      (CLL) stage Rai 0 three years previously presented in October 1998 with
      progressive disease (splenomegaly, increasing lymphocytosis: 30/nl) and 50%
      prolymphocytes in his peripheral blood. The patient was refractory to initial
      treatment with fludarabine and epirubicin, and 2-chlorodeoxyadenosine.
      Additionally, the patient developed Evans syndrome. Therapy with
      cyclophosphamide, vincristine, and prednisone lead to an improvement of
      hemolysis, but the patient remained thrombocytopenic. Subsequently, lymphocytes
      further increased to 135/nl, and cyclophosphamide 3 g/m2 was again given but
      without effect on the peripheral lymphocyte count. At this stage, therapy with
      rituximab 375 mg/m2 four times weekly was initiated. The platelet count
      normalized within 1 week after the first dose of rituximab, and the lymphocyte
      count dropped within 2 months to 1.1/nl. This case demonstrates that patients
      with prolymphocytoid transformed B-CLL refractory to purine analogs and
      alkylating agents and autoimmune-hemolytic disease can effectively and safely be
      treated with rituximab and indicates that an investigation of antibody therapy is
      warranted in this patient group.

PMID- 11320904
TI  - Central nervous system involvement in pyothorax-associated lymphoma: ring
      enhancement on CT scan.
AB  - A 71-year-old male was diagnosed as having pyothorax-associated lymphoma (PAL), a
      rare hematological malignancy associated with artificial pneumothorax for the
      treatment of pulmonary tuberculosis. Because of the low incidence, its clinical
      features have not been fully clarified. The PAL lesion in this patient
      disappeared after local radiotherapy and corticosteroid treatment. However, 8
      months after the initial diagnosis, he developed a variety of neurological
      disorders and low-grade fever. Neither recurrence of the primary pulmonary lesion
      nor nodal enlargement was observed. Immediate magnetic resonance imaging of the
      brain revealed a ring-enhanced mass, suggesting a brain abscess. However, through
      a stereotactic biopsy of the brain lesion, infiltration of PAL cells was
      identified. The brain lesion rapidly enlarged despite intensive radiotherapy, and
      he finally died of lymphoma progression. This case demonstrates that PAL may
      progress as a type of extranodal lymphoma, and that brain lesions may produce a
      ring-enhanced pattern on computed tomography.

PMID- 11320905
TI  - Candida ciferrii, a new fluconazole-resistant yeast causing systemic mycosis in
      immunocompromised patients.
AB  - Systemic infections related to fluconazole-resistant yeasts are increasingly
      observed in immunocompromised patients receiving fluconazole as a prophylactic
      antifungal treatment. Here, we report a case of invasive candidiasis caused by
      Candida ciferrii in a patient with acute myeloid leukemia and who suffered a
      relapse after autologous peripheral blood progenitor cell transplantation.
      Erythematous skin papulae and spotted pulmonary infiltrations were present. A
      skin biopsy led to the diagnosis of invasive candidiasis, emphasizing the
      diagnostic usefulness of this procedure. The yeast was identified as Candida
      ciferrii and in vitro susceptibility testing revealed its resistance to
      fluconazole. Until now, Candida ciferrii has not been known to cause invasive
      fungal infections in humans. Thus, we add another fungus to the list of
      flucanozole-resistant yeasts and suggest that in vitro susceptibility testing of
      isolated fungi should be performed for the selection of appropriate antimycotic
      drugs.

PMID- 11320906
TI  - Severe hemolytic anemia and excessive leukocytosis masking mycoplasma pneumonia.
AB  - The formation of cold agglutinins is frequently observed during Mycoplasma
      pneumoniae infections. Nevertheless, severe hemolysis is exceptional. We report a
      case of life-threatening hemolytic anemia caused by M. pneumoniae. As the
      leucocyte count was excessively elevated, the differential diagnosis primarily
      comprised hematological malignancies. The presence of cold agglutinins indicated
      the correct diagnosis, which was confirmed by highly elevated levels of both IgG
      and IgM antibodies to M. pneumoniae and a chest X-ray suggestive of atypical
      pneumonia. The patient was treated with roxithromycin and showed a favorable
      recovery within ten days after admission. This case demonstrates that, even in
      patients with clinically mild pneumonia, M. pneumoniae may be the cause of severe
      anemia.

PMID- 11320907
TI  - Hemophagocytic syndrome associated with B cell lymphoma in a patient with
      mitochondrial diabetes.

PMID- 11320908
TI  - New structures and new perspectives for Social and Preventive Medicine: the
      International Journal of Public Health.

PMID- 11320909
TI  - A worksite intervention module encouraging the use of stairs: results and
      evaluation issues.
AB  - OBJECTIVES: Recent recommendations suggest that health benefits can also be
      derived from regular daily activities of moderate intensity which accelerate
      breathing, such as climbing stairs. The purpose of this study was to examine the
      effect of an intervention programme on behaviour change in stair use in a working
      environment. METHODS: Intervention field workers were instructed to offer
      attractive or pull actions. 338 employees of four offices of the Swiss federal
      government were involved in the evaluation. Two methods were used to assess stair
      and lift use both before and after the four month intervention period: a non
      covered personal observation and an automatic measurement. RESULTS: Taking all
      four offices together, a significant increase in stair use, from 61.8% to 67.1%
      (p = 0.028), was found between the baseline and the follow-up observation. The
      automatic measurement during observation time reveals a change in stair use from
      68.8% to 71.4% (p = 0.268). The pattern of stair use examined for 24 hours by
      automatic means, however, was not so consistent. Due to the proportion of stair
      use in each office it is assumed that environmental factors influences the
      behaviour. The highest percentage of stair use at baseline (86.2%) was identified
      in an office with a bright stairwell and a small number of steps between floors.
      The lowest proportion (31.4%) was observed in an office with a dark stairwell, a
      large number of steps between floors and a stairwell accessible only with a key.
      CONCLUSIONS: However, our findings indicate that intervention with "rewarding"
      elements encourage individuals to use stairs.

PMID- 11320910
TI  - "Getting Switzerland to move": evaluation of a new "Sport for All" programme.
AB  - OBJECTIVES: Even though sports participation in Switzerland appears to be quite
      elevated, recent research suggests that only about a third of the population are
      doing enough sports from a health perspective. METHODS: Against this background
      several Swiss health insurance companies together with the Swiss Olympic
      Association have recently developed a novel approach to get people to start
      physical exercise: Under the label of "Allez Hopl" sport clubs offer training and
      information courses aimed at motivating and helping previously inactive people to
      take on regular exercise. RESULTS: The paper presents results from an
      interdisciplinary evaluation of the first three years of the "Allez Hopl"
      campaign. Starting from an overview of the basic idea and features of the
      campaign it asks whether "Allez Hopl" has reached its self-declared goal of
      "getting Switzerland moving". Available evidence on the social background of
      participants and their further activities shows that by systematically avoiding
      any reference to conventional notions of sport and by stressing the health and
      fun aspect instead. "Allez Hopl" has indeed managed to mobilise an important
      group with under-average levels of activity (particularly middle-aged women). In
      addition, on average the level of physical exercise of participants appears to
      have increased. Yet, the number of participants is below the original target
      values and, contrary to the campaign's initial goal, participants are reluctant
      to leave the programme after one course to take up an independent activity or to
      join a club. CONCLUSIONS: The paper explores the achievements and problems of the
      campaign so far and offers an explanation of recent problems which can also serve
      as a basis for the implementation of similar programmes in other countries.

PMID- 11320911
TI  - [Health promotion by sports and physical activity: politics, behavior and
      infrastructures in a European comparison].
AB  - OBJECTIVES: The focus of physical activity promotion is moving from measures to
      increase health-enhancing physical activity on the individual level to higher
      level strategies including policy and environmental approaches. Scientific
      evidence, traditionally related to individual-based strategies, calls for
      adaptation and refinement when environmental and policy changes become more
      relevant. METHODS: This paper investigates differences in physical activity
      promotion and public policy among six European countries. Data from a European
      study on public health promotion policy and health behaviours (MAREPS) is
      analysed to study behaviour, community-based opportunities for physical activity,
      and populations' perception of the effectiveness of their national policies in
      promoting physical activity. RESULTS: Analyses show significant differences in
      both involvement in and perceived opportunities for physical activity among the
      investigated countries. Populations in Finland, Switzerland, and The Netherlands
      show comparably higher participation and, at the same time, perceive better
      opportunities for physical activity within the residential environment than
      people in East Germany, Belgium, and Spain. Moreover, respondents from the former
      group of nations report considerably greater contribution of health policy in
      their country to the promotion of physical activity than respondents from the
      latter group. CONCLUSIONS: In conclusion, the results provide empirical support
      for the significance of environmental and policy approaches with regard to
      physical activity. Opportunities created by implementing such approaches may
      enable populations to develop more active lifestyles conducive to health. Further
      research employing longitudinal designs could be especially helpful to explore
      the causalities of the relationship between policy, environment and physical
      activity.

PMID- 11320912
TI  - [Sports and physical activity in the elderly: social structural context and
      relation to health].
AB  - OBJECTIVES: The following contribution analyses the socio-structural context of
      sport as well as the relationship between sport/physical activity and health
      among older people (> or = 60 years). METHODS: The data are part of a telephone
      survey by random sample with 436 realised cases in the independent cities of the
      Western Ruhr-District and thus represent a situation in highly urbanised areas.
      RESULTS: In the cardinal question concerning the meaning of sport and physical
      activity for health a positive relationship was found, in particular between
      sport intensity and health measured by Advanced Activities of Daily Living (AADL)
      as well as for sport as hobby, which showed a highly significant relationship
      with subjective health. With regard to socio-demographic variables results show
      that sport and physical activity vary with gender and age. Apart from that
      attitudes like low external control for one's health as well as the value of
      appearance show strong relationships with sport participation. Stratification
      variables with the exception of income only show weak effects. CONCLUSIONS: The
      results, which are partly not congruent, indicate that further research is needed
      in the field of sport and health among the aged.

PMID- 11320913
TI  - Physical activity of urban adults: a general population survey in Geneva.
AB  - OBJECTIVES: Describing the distribution of physical activity in populations is of
      major importance for developing public health campaigns to prevent sedentarism.
      METHODS: A population-based survey conducted during 1997-1999 in Geneva,
      Switzerland, included 3410 randomly selected men (n = 1707) and women (n = 1703),
      aged 35 to 74 years. Percentiles P10, P50, and P90 summarised the distributions
      of the total energy expenditure and of the percents used in moderate intensity
      activities (3 to 3.9 times the basal metabolism rate (BMR), e.g., normal walking,
      household chores), and in high and very high intensity activities (> or = 4 BMR,
      e.g., brisk walking, sports). RESULTS: The total energy expenditure (median 2929
      kcal/day in men, 2212 kcal/day in women) decreased with age. Prevalence of
      sedentarism, defined as less than 10% of total energy expended in > or = 4 BMR
      activities, was 57% in men and 70% in women. Men expended 12% (median) of their
      total energy in 3 to 3.9 BMR and 8% in > or = 4 BMR activities. Corresponding
      percentages in women were 11% and 5%. The highest prevalence of sedentarism was
      in older age, women, and lower socio-economic status persons. CONCLUSION: Most of
      Geneva population is sedentary. Promoting physical activity should target
      children, adults and elderly, and physical activities which would be both
      attractive and financially affordable by most people.

PMID- 11320914
TI  - [Physical activity and health].

PMID- 11320915
TI  - Cohort analysis: W.H. Frost's contributions to the epidemiology of tuberculosis
      and chronic disease.
AB  - Although Wade Hampton Frost was not the first to develop cohort analysis, it was
      the post-humous publication of his study of age and time trends of tuberculosis
      mortality that directed attention to this method of analysis. Frost's developing
      interest in and contributions to the epidemiology of chronic disease are reviewed
      in connection with a summary of his professional career.

PMID- 11320916
TI  - Is a palpable short saphenous vein a useful clinical sign in varicose vein
      assessment?
AB  - The short saphenous vein (SSV) may be palpable in the popliteal fossa in patients
      with varicose veins. A prospective study has been carried out to determine the
      significance of this sign in the presence of primary varicose veins. The SSV was
      assessed by palpation of the popliteal fossa with the knee slightly flexed. Hand
      held Doppler insonation (HHD) was also used in the out-patient clinic. All
      patients had SSV assessment by duplex scanning. One hundred and sixty legs were
      examined. In 68 the SSV was palpable; 39 (57%) of these had SSV reflux on duplex
      examination. When the SSV was not palpable (92 legs), only 1% (1 leg) refluxed on
      duplex scanning. SSV palpability had a 98% sensitivity, 75% specificity, 57%
      positive predictive value (PPV), and 99% negative predictive value (NPV). In
      comparison, HHD had 80% sensitivity, 87% specificity, 67% PPV and 93% NPV. The
      combined tests had 78% sensitivity, 73% specificity, 76% PPV and 100% NPV.
      Palpation of the SSV is a valuable part of clinical examination. If the SSV is
      not palpable, it is unlikely to reflux.

PMID- 11320917
TI  - Can breast surgeons read mammograms of symptomatic patients in the one-stop
      breast clinic?
AB  - AIM: To establish how accurate surgeons were when compared to the radiologists in
      interpreting symptomatic mammograms in one-stop clinics. METHODS: The surgeons
      were asked to write their opinion on the mammograms which was compared with the
      radiologists' report. 144 patients were involved in the study and the data were
      analysed by McNemara's test for paired categorical data. RESULTS AND CONCLUSIONS:
      Surgeons were accurate in interpreting most of the mammographic findings.
      However, they underestimated the presence of benign calcification which was
      statistically significant. Surgeons can, therefore, be involved in double reading
      of mammograms in symptomatic breast disease patients and improve the sensitivity
      which has been the case in double reading by radiologists in the breast screening
      programme.

PMID- 11320918
TI  - Replace fine needle aspiration cytology with automated core biopsy in the triple
      assessment of breast cancer.
AB  - All patients presenting with a symptomatic breast lump are assessed by means of
      triple assessment (clinical examination, radiology in the form of mammography and
      cytology by means of a fine needle aspiration) performed by the clinician in the
      rapid access breast clinic at the Royal Gwent Hospital, Newport, UK. In our
      initial experience, it was found that a significant number of patients were
      returning to clinic for the results of the triple assessment to find that the
      cytology was not conclusive and hence needed a core biopsy, thus delaying
      diagnosis and definitive treatment. Therefore, a prospective study was carried
      out over a 6-month period, where all patients presenting with a symptomatic lump
      with a clinical or radiological suspicion of breast cancer had, in addition to
      the standard triple assessment, an automated core biopsy, thus giving rise to the
      quadruple assessment of the breast lump. A total of 52 patients with a clinical
      or radiological suspicion of breast cancer were included over this 6-month
      period. Of these 52 patients, 31 had a definitive diagnosis of breast cancer on
      fine needle aspiration (sensitivity 60%) compared with 50 of the 52 patients on
      core biopsy (sensitivity 96%). When radiology was diagnostic of breast cancer (R
      5), the sensitivity of cytology was 61% compared with 97% with core biopsy.
      However, when radiology was not diagnostic of cancer (R 1-4), the sensitivity of
      cytology fell to 53% while the sensitivity of core biopsy remained high at 95%.
      The overall cellularity rate for cytology was 96%, which exceeds the BASO
      requirement for fine needle aspiration cytology. From these results, we conclude
      that automated core biopsy has a superior diagnostic power when compared with
      fine needle aspiration cytology and hence should replace fine needle aspiration
      cytology in the assessment of symptomatic breast lumps.

PMID- 11320919
TI  - Why should diagnostic benign breast biopsies weight less than twenty grams?
AB  - To reduce the cosmetic deformity resulting from diagnostic biopsies, current
      breast screening guidelines recommend that 80% of biopsy specimens that
      subsequently prove to be benign should weigh less than 20 g. The relationship
      between specimen weight and cosmesis is unknown and evidence to support a 20 g
      upper limit is lacking. Patient satisfaction following all benign biopsies
      weighing more than 20 g (n = 49) and a random sample of 30 of those weighing less
      than 20 g (n = 103) performed by one screening unit, over a 6 year period, was
      assessed by a postal questionnaire. Overall, 32% of patients were unhappy with
      the cosmetic outcome of their surgery. Patient dissatisfaction appeared to
      increase with specimen weight (6/23 [26%] < 20 g versus 13/36 [36%] > 20 g) but
      no statistically significant relationship between weight and cosmesis was
      apparent (P = 0.57). Reducing benign breast biopsy specimen weights to a minimum
      is a desirable objective. However, the current quality standard is not evidence
      based, is too stringent and should be revised. Strategies need to be introduced
      to improve patient satisfaction following breast wire-localisation biopsies. In
      particular, patients should be counselled pre-operatively regarding possible
      adverse cosmetic outcome.

PMID- 11320920
TI  - The next millennium--are we becoming emergency surgeons? A seven year audit of
      surgical and urological admissions in a rural district general hospital.

PMID- 11320921
TI  - Circumcision: a refined technique and 5 year review.
AB  - The vast majority of circumcisions currently performed in the UK are for phimosis
      or balanitis and the patients are not looking for the denuded glans appearance of
      a ritual circumcision. We present a refinement of the sleeve technique of
      circumcision, which involves Horton's test to define the proximal incision
      margin, and bipolar electro-dissection. A review of all patients undergoing
      circumcision at the Wordsley Plastic Surgery Unit, in a 5-year period, has shown
      this technique to be safe with a haematoma rate of only 1.4%, and an overall
      complication rate of 3%.

PMID- 11320922
TI  - Modified puncture technique for reduction of paraphymosis.
AB  - PATIENTS AND METHODS: A total of 45 patients underwent reduction of paraphymosis
      at LN Hospital, Delhi, India and Leighton Hospital, Crewe, UK from August 1991 to
      September 1999 using the multiple puncture and glans squeeze technique. These
      were divided into 3 grades: grade 1, paraphymosis without engorgement of glans;
      grade 2, paraphymosis with engorgement of glans; and grade 3, paraphymosis with
      associated skin changes (non-pitting oedema, cheese-cutting of the shaft of the
      penis or erosions). RESULTS: Grade 1 (6) patients were reduced by simply pulling
      the foreskin back into the normal position. Grade 2 (37) patients were reduced by
      the above-mentioned technique. Grade 3 (2) patients could not be reduced by this
      technique and the band had to be divided. CONCLUSIONS: Difficult paraphymosis
      with gross engorgement of the glans can be successfully reduced by this technique
      as long as the skin changes are not marked.

PMID- 11320923
TI  - Disability and mental health of patients waiting for total hip replacement.
AB  - We performed a cross sectional study to examine the relationship between physical
      function and mental health of patients waiting for total hip replacement surgery,
      and the relationship between physical and social function and mental health to
      time spent waiting for surgery. We found that, in addition to the expected poor
      hip function, limited mobility and pain, one-quarter of the patients had
      clinically significant mood disorders and another quarter were in the borderline
      range. No association was found between severity of mental disorder and
      assessment of hip function. The patients had been waiting for 1-26 months (median
      6 months) for surgery: yet those waiting longest were no worse on any of the
      outcome measures and their mental health was better. We conclude that mental
      disorders are common in patients waiting for hip replacements, are not directly
      related to hip function and their origins are unknown, but they require clinical
      assessment and treatment. There is no evidence that physical or social function
      or mental health are worse in those waiting longer for hip replacement surgery.
      Even so, these patients are severely disabled and some have to wait too long.

PMID- 11320924
TI  - Laparoscopic forceps--a useful tool in revision hip arthroplasty.
AB  - During revision hip arthroplasty, distal cement plugs and broken instrument tips
      in the femoral canal pose quite a challenge. We report the use of laparoscopic
      forceps to facilitate their removal thereby avoiding complications associated
      with other methods previously described.

PMID- 11320925
TI  - Dog ear: an overview of causes and treatment.
AB  - Dog ear is a term used to describe a characteristic puckering of the skin that
      can occur after surgical wound closure. Every surgeon practising cutaneous
      surgery should be conversant with dog ears as they are a common and generally
      preventable problem. They are significant as they may mar an otherwise excellent
      aesthetic outcome and may, on occasions, require revisional surgery.

PMID- 11320926
TI  - Correlation between psychometric test scores and learning tying of surgical reef
      knots.
AB  - We have investigated the correlation between the scores attained on a
      computerised psychometric test, measuring psychomotor aptitude and learning tying
      of a surgical reef knot. Fifteen surgical trainees performed a test of
      psychomotor aptitude (ADTRACK 2) from the MICROPAT testing system. They then
      performed a simple test of their ability to tie a surgical reef knot and were
      assessed by a panel of experts prior to embarking on a standardised course of
      instruction and practice session. The knot-tying test was repeated at the end of
      the day and the differences in average scores recorded. There was a significant
      correlation between the means of the differences in knot tying scores and ADTRACK
      2 scores (r = -0.533, P < 0.05). Psychomotor abilities appear to be determinants
      of trainees' initial proficiency in learning to tie a surgical reef knot.

PMID- 11320927
TI  - Percutaneous (Portex) tracheostomy: an audit of the Newcastle experience.

PMID- 11320928
TI  - Management of isolated sternal fractures: determining the risk of blunt cardiac
      injury.

PMID- 11320929
TI  - 'Fast track' carotid duplex scanning in a district general hospital.

PMID- 11320930
TI  - 'Fast track' carotid duplex scanning in a district general hospital.

PMID- 11320931
TI  - Clinical examination of varicose veins--a validation study.

PMID- 11320932
TI  - Large bowel impaction by the BioEnterics Intragastric Balloon necessitating
      surgical intervention.

PMID- 11320933
TI  - The role of the colonic flora in maintaining a healthy large bowel mucosa.
AB  - This work explores the intricate relationships between bacterial products of
      fermentation, the short chain fatty acids and the effect that these have on the
      colonic epithelium and the immune system. It confirms that butyrate is a major
      energy source for the colonic epithelium and there may be a minor epithelial
      abnormality in the metabolism of butyrate in patients with ulcerative colitis.
      Immunological studies suggest that butyrate has an effect on lymphocyte
      activation and inhibits cell proliferation. Possibly, butyrate induces anergy in
      lymphocytes via an effect on the TCR receptor. This may represent a mechanism
      whereby colonic bacteria are able to regulate the host immune response. An
      abnormal response to butyrate may upset the homeostasis between the gut immune
      system and the colonising bacteria resulting in epithelial unrest and
      inflammation.

PMID- 11320934
TI  - Oophorectomy in primary colorectal cancer.
AB  - Colorectal cancer is a common cancer affecting women which may metastasize to the
      ovaries. We present five cases of ovarian metastases requiring surgery and review
      the debate regarding oophorectomy at the primary resection for colorectal cancer.
      Although prophylactic oophorectomy has not been proven to affect survival,
      further surgery for symptomatic ovarian metastases may be avoided and the
      increased risk of developing primary ovarian cancer is abolished.

PMID- 11320935
TI  - Neo-adjuvant therapy improves resectability rates for colorectal liver
      metastases.
AB  - PURPOSE: Liver resection improves survival in selected patients with colorectal
      liver metastases. However, the majority of patients with colorectal liver
      metastases have inoperable disease at presentation. Neo-adjuvant therapy
      (systemic or regional chemotherapy and interstitial laser therapy) used singly or
      in combination may convert a selected group of patients with irresectable liver
      metastases into an operable state. PATIENTS AND METHODS: We report a series of
      patients with initially inoperable multiple colorectal liver metastases who
      became operable after neo-adjuvant therapy. Operability was defined as unilateral
      disease limited to the liver. Twelve patients (7 female, 5 male, median age 57
      years, range 38-69 years) with multiple inoperable colorectal liver metastases (8
      synchronous, 4 metachronous) were initially treated with systemic chemotherapy (n
      = 7), hepatic arterial chemotherapy (n = 2) and chemotherapy plus interstitial
      laser therapy (n = 3). RESULTS: In all cases, a significant response was achieved
      which enabled subsequent liver resection to be undertaken. There was only one
      postoperative complication (8%) and no peri-operative deaths. 3 patients were
      operated on within the last 12 months and are still alive. Of the remainder, 1
      died within 1 year with recurrent disease. The remaining patients have a median
      survival of 2.5 years, range 1.39-4 years. CONCLUSIONS: These results are similar
      to those reported for patients undergoing resection for operable metastases
      without neo-adjuvant therapy. Aggressive multimodality treatment of colorectal
      liver metastases in specialised centres may improve the resectability rates and
      survival in a selected group of patients.

PMID- 11320936
TI  - Cadaveric dissection for the rectal surgeon.
AB  - The benefits of total mesorectal excision are due to the complete excision of the
      mesorectum with preservation of the pelvic autonomic nerve plexuses, the
      hypogastric nerves and nervi erigentes. Several important structures are
      incompletely seen at operation, and cadaveric dissection of an intact lower trunk
      and a sagittally hemisected pelvis is a valuable exercise in demonstrating them.
      A method for dissection is described which illustrates the key anatomical points.

PMID- 11320938
TI  - From catsup to salsa: a revised vision of multiculturalism.

PMID- 11320939
TI  - Herbal foods: health and happiness on a corn flake?

PMID- 11320937
TI  - Spontaneous common iliac arteries rupture in Ehlers-Danlos syndrome type IV:
      report of two cases and review of the literature.
AB  - Two patients with previously undiagnosed Ehlers-Danlos syndrome type IV (EDS IV)
      presented acutely with clinical features suggestive of hypovolemic shock.
      Emergency laparotomies in both of them revealed spontaneous rupture of the common
      iliac arteries. The clinical features, operative findings, surgical approach,
      outcome and implications are discussed.

PMID- 11320940
TI  - Dietitian business Web sites: a survey of their profitability and how you can
      make yours profitable.

PMID- 11320941
TI  - Avocado fruit is a rich source of beta-sitosterol.

PMID- 11320942
TI  - An international dietetics internship experience.

PMID- 11320943
TI  - ADA's historic commitment to improve nutrition policy.

PMID- 11320944
TI  - MNT: success means ongoing effort.

PMID- 11320945
TI  - What we know for sure.

PMID- 11320946
TI  - Popular diets: correlation to health, nutrition, and obesity.
AB  - OBJECTIVE: To examine the association between a range of health and nutrition
      indicators and popular diets. DESIGN: The Continuing Survey of Food Intake by
      Individuals (CSFII) 1994-1996 data were used to examine the relationship between
      prototype popular diets and diet quality as measured by the healthy eating index
      (HEI), consumption patterns, and body mass index (BMI). The prototype diets
      included vegetarian (no meat, poultry, or fish on day of survey) and non
      vegetarian. The nonvegetarian group was further subdivided into low carbohydrate
      (less than 30% of energy from carbohydrate), medium (30% to 55%), and high
      (greater than 55% of energy). Within the high carbohydrate group, participants
      were classified as having Pyramid or non-Pyramid eating patterns. The Pyramid
      group was defined as 30% or less of energy from fat and at least one serving from
      the five major food groups in the USDA Food Guide Pyramid. Finally, the non
      Pyramid group was further subdivided into low fat (less than 15% of energy from
      fat) and moderate fat (15% to 30% of energy from fat). In addition, a review of
      the published scientific literature was conducted; all studies identified were
      included in the review. SUBJECTS: 10,014 adults, aged 19 years and older, from
      the 1994-1996 CSFII were included in the analyses of extant data. More than 200
      individual studies were included in the review of the literature. RESULTS:
      Analyses of the CSFII indicate that diet quality as measured by HEI was highest
      for the high carbohydrate Pyramid group (82.9) and lowest for the low
      carbohydrate group (44.6). Energy intakes were low for the vegetarians (1,606
      kcals) and high carbohydrate/low fat group (1360 kcals). BMIs were lowest for
      women in the vegetarian group (24.6) and the high carbohydrate/low fat group
      (24.4); for men, the lowest BMIs were observed for vegetarians (25.2) and the
      high carbohydrate Pyramid group (25.2). Review of the literature suggests that
      weight loss is independent of diet composition. Energy restriction is the key
      variable associated with weight reduction in the short term. CONCLUSIONS: Diets
      that are high in carbohydrate and low to moderate in fat tend to be lower in
      energy. The lowest energy intakes were observed for those on a vegetarian diet.
      The diet quality as measured by HEI was highest for the high carbohydrate groups
      and lowest for the low carbohydrate groups. The BMIs were significantly lower for
      men and women on the high carbohydrate diet; the highest BMIs were noted for
      those on a low carbohydrate diet.

PMID- 11320947
TI  - Change in women's diet and body mass following intensive intervention for early
      stage breast cancer.
AB  - OBJECTIVE: To determine the effectiveness of an intensive dietary intervention on
      diet and body mass in women with breast cancer. DESIGN: Randomized clinical
      trial. SUBJECTS: 172 women aged 20 to 65 years with stage I or II breast cancer.
      INTERVENTION: A 15-session, mainly group-based and dietitian-led nutrition
      education program (NEP) was compared to a mindfulness-based stress reduction
      clinic program (SRC); or usual supportive care (UC). MAIN OUTCOME MEASURES:
      Dietary fat, complex carbohydrates, fiber, and body mass were measured.
      STATISTICAL ANALYSIS: In addition to descriptive statistics, analysis of variance
      was conducted to test for differences according to intervention group. RESULTS:
      Of the 157 women with complete dietary data at baseline, 149 had complete data
      immediately postintervention (at 4 months) and 146 had complete data at 1 year.
      Women randomized to NEP (n = 50) experienced a large reduction in fat consumption
      (5.8% of energy as fat) at 4 months and much of this reduction was preserved at 1
      year (4.1% of energy) (both P < .0002) vs no change in either SRC (n = 51) or UC
      (n = 56). A 1.3-kg reduction in body mass was evident at 4 months in the NEP
      group (P = .003) vs no change in the SRC and UC groups. Women who had higher-than
      average expectations of a beneficial effect of the intervention experienced
      larger changes. APPLICATIONS: Dietitians' use of group nutrition interventions
      appear to be warranted. Increasing their effectiveness and maintaining high
      levels of adherence may require additional support, including the involvement of
      significant others, periodic individual meetings, or group booster sessions.

PMID- 11320948
TI  - A longitudinal study of children's juice intake and growth: the juice controversy
      revisited.
AB  - OBJECTIVES: To determine associations between children's longitudinal juice
      intake and growth parameters at age 72 months and to determine children's
      beverage intake patterns over time. SUBJECTS/SETTING: White children (n = 72)
      residing in the vicinity of a Southern US city participated in a longitudinal
      study. METHODS: Seven in-home interviews were conducted per child when each child
      was between 24 and 72 months of age. The 7 sets of 3-day dietary data were
      analyzed for beverage intake, categorized as juice (100% juice only), milk,
      carbonated beverages, and other drinks (e.g., lemonade, tea, juice drinks). The
      following growth parameters were determined for each child at age 72 months:
      height, weight, body mass index (measured as kg/m2), and ponderal index (measured
      as kg/m3); the 3 latter are measures of overweight. STATISTICAL ANALYSES:
      Associations between longitudinal juice intake and each growth parameter were
      tested with general linear models. Repeated measures analysis of variance tested
      changes in beverage intakes over time. RESULTS: There were no statistically
      significant associations between juice and children's height, weight, or body
      mass index, as tested by general linear models. Children's longitudinal juice
      intake was negatively related to ponderal index (beta = 0.065, P = .050).
      Children's juice intake decreased significantly between ages 2 and 6 years, from
      6.8 to 3.6 oz/day (P = .0001); intakes of carbonated beverages and other drinks
      increased from 1.7 to 3.8 oz/day (P = .0016) and from 2.7 to 6.2 oz/day (P =
      .0001), respectively. APPLICATIONS/CONCLUSIONS: Children's longitudinal juice
      intake was not associated with either short stature or overweight. As juice
      consumption decreased, intakes of less nutritious beverages increased.
      Consumption of 100% juices should be encouraged by health professionals and
      parents/caregivers.

PMID- 11320949
TI  - Getting back to basics: tips for squeezing by the juice controversy.

PMID- 11320950
TI  - Stature as a prognostic factor in cystic fibrosis survival.
AB  - OBJECTIVE/DESIGN: This study provides a longitudinal analysis of the National
      Cystic Fibrosis Patient Registry to determine if height-for-age percentile would
      be a useful predictor of survival. SUBJECTS: All patients were selected from the
      national registry (n = 19,000) maintained by the Cystic Fibrosis Foundation's 115
      accredited Cystic Fibrosis Care Centers in the United States. Inclusion in our
      analysis required that subjects were born between 1980 and 1989; had a minimum of
      4 records each; the subject was alive at age 7; and the subject had a recorded
      height measurement at age 7 to 8 (n = 2,773). STATISTICAL ANALYSIS: The Cox
      proportional hazards model was used to compare height-for-age with survival. We
      recorded whether a subject was less than the 5th National Center for Health
      Statistics (NCHS) percentile at age 5 and then in a separate analysis at age 7.
      Cohort effect was coded as "1" if they were born before 1982 and "0" otherwise.
      RESULTS: Stature is a significant prognostic indicator of survival. The relative
      hazard associated with height below the 5th NCHS percentile for age was
      significant for both males and females. In males at age 5 the relative hazard was
      2.9, [95% confidence interval (CI) 1.23, 6.91; P < .02] and at age 7 it was 6.3
      (95% CI 2.1, 18.8; P < .001). The relative hazard in females at age 5 was 4.3
      (95% CI 2.4, 7.3; P < .0001) and at age 7 was 5.8 (95% CI 2.5, 13.1; P < .0001).
      APPLICATION: These highly significant relative hazard values strongly suggest
      that shorter patients are much more likely to die before taller patients. The
      dietetic professional should consider using height-for-age as an effective
      screening tool to identify patients at risk. Based on these data, short stature
      should not be considered benign to patients with cystic fibrosis. The CF team,
      clinicians, family, and patients need work together to maximize linear growth
      through medical and nutritional intervention.

PMID- 11320951
TI  - Effect of timing of introduction of complementary foods on iron and zinc status
      of formula fed infants at 12, 24, and 36 months of age.
AB  - OBJECTIVE: The timing of introduction of complementary food to an infant's diet
      is variable throughout the world. Our objective was to determine whether early
      introduction of complementary foods affects iron and zinc status of formulated
      infants at 12, 24, and 36 months of age. DESIGN: A randomized, prospective trial
      was conducted. Infants were randomly assigned to receive either a) early
      introduction (at 3 to 4 months of age) of commercially prepared or parent's
      choice of complementary foods; or b) late introduction (at 6 months of age) of
      commercially prepared complementary foods or parent's choice of complementary
      foods. In addition to complementary foods, infants were fed commercial infant
      formula as recommended by their pediatrician. Hemoglobin, mean corpuscular
      volume, and serum ferritin and zinc concentrations were determined at 12, 24, and
      36 months of age. Three-day diet diaries were completed at 3, 6, 12, 18, 24, 30,
      and 36 months of age. SUBJECTS/SETTING: One hundred seventy-five infants younger
      than 3 months were recruited by mailings to parents in the Cincinnati area. Of
      these, 172 were enrolled, 90 in the early-introduction group and 82 in the late
      introduction group. One hundred thirty-three infants (n = 67 in the early, n = 66
      in the late group) completed the study. STATISTICAL ANALYSES PERFORMED: Student t
      test and regression analyses were used to determine whether there were group
      differences and whether there was a relationship between serum parameters and
      dietary intake. RESULTS: Infants fed complementary foods early had significantly
      greater iron intakes until 6 months of age; however, there were no differences in
      the iron status parameters (ferritin, hemoglobin, and mean corpuscular volume) at
      12, 24, or 36 months of age. The early introduction group consumed slightly less
      zinc than the late introduction group at 5 months (4.4 vs 4.8 mg/day, P < .01)
      and 6 months (4.4 vs 4.7 mg/day, P < .01). At all other times there were no
      differences between the early and late group in zinc intakes. The serum zinc
      concentration was not associated with dietary zinc. Both groups had normal serum
      zinc concentrations at 12, 24, and 36 months and there were no differences
      between groups. APPLICATIONS/CONCLUSIONS: The iron and zinc status of infants in
      this study was not influenced by the timing or type of complementary foods
      introduced. However, the infants were formula fed and the mean iron and zinc
      intakes that were equal or greater than the Recommended Dietary Allowances for
      the first 6 months of age.

PMID- 11320952
TI  - Bulimia nervosa during pregnancy: a review.
AB  - Pregnant women with bulimia nervosa present interesting practice challenges for
      dietitians and healthcare professionals due to potential complications of bulimia
      nervosa for both mothers and fetuses. This review summarizes case study reports,
      case series reports, and retrospective studies of women with bulimia nervosa
      during pregnancy, and focuses on relationships among bulimic behaviors, pregnancy
      results, and birth outcomes. Pregnancy and birth outcomes of women with bulimia
      nervosa varied among individuals and studies. Material outcomes of concern
      included miscarriages, inappropriate weight gains (excessive or inadequate),
      complicated deliveries, and resumed and/or continued bulimic behaviors shortly
      after parturition. Fetal complications included low birth weights, prematurity,
      malformations, and low Apgar scores. Screening to detect bulimic behaviors is
      recommended, as is multidisciplinary treatment of pregnant women with bulimia
      nervosa to emphasize adequate dietary intakes, promote appropriate weight gains,
      and help achieve healthy infant outcomes in addition to long-term, healthy eating
      habits for these women. Future research regarding maternal and fetal outcomes of
      women with bulimia nervosa during pregnancy, conducted by registered dietitians,
      is needed to provide greater clarity and understanding of the impact of bulimic
      behaviors, dietary intakes, and nutritional status during pregnancy on maternal
      and fetal health.

PMID- 11320953
TI  - Assessment of the effect of fat-modified foods on diet quality in adults, 19 to
      50 years, using data from the Continuing Survey of Food Intake by Individuals.
AB  - Fat-reduction strategies and the role of fat-modified foods in the US diet were
      assessed using a nationally representative survey: the 1996 US Department of
      Agriculture Continuing Survey of Food Intakes by Individuals. A sample of 878 men
      and 853 women was included. The sample was divided into low fat and high fat
      based on the Dietary Guideline's cutoff poin of 30% or less of energy from total
      fat. The survey sample was further stratified in nonusers, low-users or high
      users of fat-modified foods. Approximately 10% of 7,000 foods were classified as
      fat-modified. There was a 400 to 500 kcal difference in energy intake of
      individuals consuming low-fat compared with high-fat diets. Adults who were users
      of fat-modified foods consumed more nutrient-dense diets, with higher intakes of
      vitamin A, folate, and iron. Not all fat-reduction strategies were equally
      effective in reducing fat and maintaining nutrient intake. Nonusers of fat
      modified foods who consumed a low-fat diet tended to do so by substituting
      carbohydrate, in part from carbonated beverages, for fat. Both men and women
      consuming a low-fat diet had lower average BMIs; this difference between
      individuals consuming low-fat vs high-fat diets was significant for women who
      were high-users of fat-modified foods. The data suggest that a low-fat diet with
      high use of fat-modified foods may be one strategy for achieving adequate
      nutrient intake while maintaining weight in the desirable BMI range of 19 to 25.

PMID- 11320954
TI  - Soy protein lowers fat and saturated fat in school lunch beef and pork entrees.

PMID- 11320955
TI  - Use of low-fat milk by children in the New York State WIC varies with parental
      characteristics.

PMID- 11320956
TI  - Acceptability of peanut butter cookies prepared using mungbean paste as a fat
      ingredient substitute.

PMID- 11320957
TI  - Size categories most effective for estimating portion size of muffins.

PMID- 11320959
TI  - MedBytes.

PMID- 11320958
TI  - Standards of professional practice: measuring the beliefs and realities of
      Consultant Dietitians in Health Care Facilities.
AB  - A dietetic practice group of the American Dietetic Association (ADA), Consultant
      Dietitians in Health Care Facilities (CD-HCF), surveyed members (n = 5930) on
      agreement with the six standards of professional practice and frequency of
      completing indicators within each standard. Sampling approaches included placing
      a survey in the publication, The Consultant Dietitian, and disseminating at the
      following CD-HCF activities: the 1998 business meeting at ADA's Annual Meeting &
      Exhibition, a multi-state teleconference in December 1998, and conferences held
      between November 1998 to April 1999. Duplication was monitored using the RD or RD
      eligible registration number. The final sample included 553 surveys and
      represented 10% of the membership. Of the survey responders, 50% were individual
      consultants and 43% were employees; 88% consulted to facilities providing skilled
      care (geriatrics/adults) and 48% consulted to intermediate care facilities. With
      the exception of one, all standards and indicators met acceptance criterion. The
      standard statement "participation in research to enhance practice" did not attain
      the validation criterion. Study findings indicated that consulting to a facility
      conducting nutrition research increased chances of agreement with the research
      participation standard. The Executive Committee approved all standards,
      indicators and outcomes as a document defining quality consultation and business
      services conduct for consultant dietitians in health care facilities.

PMID- 11320960
TI  - Managed care under repair.

PMID- 11320961
TI  - Blue Cross blues.

PMID- 11320962
TI  - Full disclosure.

PMID- 11320963
TI  - The screaming silence.

PMID- 11320964
TI  - Teaching to heal. Part 1.

PMID- 11320965
TI  - Trends in the incidence of hepatitis A in Texas, 1986 through 1997.
AB  - Hepatitis A is one of the most common infections reported in Texas. This study
      examined the trends in incidence of hepatitis A in Texas for the years from 1986
      through 1997. Demographic and clinical data of reported cases were obtained from
      the Texas Department of Health. Population estimates were obtained from Epigram.
      Rates were calculated per 100,000 population. For the 1986-1997 period, 33,833
      cases of acute hepatitis A were reported. Rates varied considerably by ethnicity
      and race: Hispanics had the highest average annual rate (32.2 per 100,000),
      followed by non-Hispanic whites (8.2 per 100,000) and African Americans (6.0 per
      100,000). The rate for Hispanics was more than two times higher than the rates
      for non-Hispanic whites and African Americans in all 11 public health regions in
      Texas. Children aged 5 through 9 years had the highest rates of hepatitis A. The
      3-month period from August through October had the largest reported number of
      onsets of hepatitis A (P < .01).

PMID- 11320966
TI  - [Screening tests "ImmunoKhrom-anti-MT-Ekspress" in postmortal diagnosis of
      tuberculosis].

PMID- 11320967
TI  - [59th Annual Meeting of the Japanese Cancer Association. October 4-6, 2000.
      Yokohama, Japan. Abstracts].

PMID- 11320968
TI  - [28th Annual meeting of the Austrian Diabetes Society. Baden bei Wien, 30
      November-2 December 2000. Abstracts].

PMID- 11320969
TI  - FDI Paris 2000 Congress. Abstracts.

PMID- 11320970
TI  - [Academic Conference of the Polish Society of Neurology Section on Extrapyramidal
      Diseases. Jachranka, 22-24 September 2000. Abstracts].

PMID- 11320971
TI  - Lumbar discectomy and the diabetic patient: incidence and outcome.
AB  - Medical records of 363 patients who had a diagnosis of lumbar disc disease and
      were managed by a posterior approach lumbar discectomy over a 7 year period were
      reviewed: 33 patients had a preoperative diagnosis of diabetes, an incidence in
      this patient population of 9.1%. The results for these 33 patients who had a
      diagnosis of diabetes mellitus were compared with those of 33 age and sex matched
      nondiabetic (control) patients who had a similar operative approach. Twenty-five
      of the diabetic and 28 of t he control patients were available for long term
      follow up. The results were positive (good to excellent) for 24 of the 28 (86%)
      control patients and 15 of the 25 (60%) diabetic patients. Seven of the 25 (28%)
      diabetic patients had reoperation for recurrent disc herniation at the same level
      following the initial procedure compared with one of the 28 (3.5%) control
      patients.

PMID- 11320973
TI  - Adolescent health. Bibliography of journal articles (July to December 1999).

PMID- 11320972
TI  - Inter-rater reliability of stroke sub-type classification by neurologists and
      nurses within a community-based stroke incidence study.
AB  - The stroke classification developed for use in the Oxfordshire Community Stroke
      Project (OCSP) is simple, clinically meaningful and requires no investigations.
      However, its inter-rater reliability in a community setting is unknown. We aimed
      to assess the inter-rater reliability of this classification among neurologists
      and nurses within a community-based stroke incidence study. Fifty-four stroke
      patients with cerebral infarction who were registered in the North East Melbourne
      Stroke Incidence Study (NEMESIS) were assigned OCSP classifications by two
      neurologists and one of seven research nurses. There was moderate agreement
      between neurologists (kappa = 0.53), fair agreement between neurologist 1 and
      nurse (kappa = 0.31) and moderate agreement between neurologist 2 and nurse
      (kappa = 0.45). Disagreement about the neurological signs was an important reason
      for classification differences. The OCSP classification can be easily applied in
      a community setting with moderate inter-rater reliability and is thus a useful
      instrument for commun ity-based epidemiological studies.

PMID- 11320974
TI  - Changing the focus: resiliency and youth development. Annual meeting of the
      Society for Adolescent Medicine. San Diego, California, USA. March 21-25, 2001.
      Abstracts.

PMID- 11320975
TI  - 27th Annual Meeting of The Japanese Society of Toxicology. June 28-30, 2000.
      Yokohama, Japan. Abstracts.

PMID- 11320977
TI  - APICON 98. 53rd Joint Annual Conference. Bangalore, India. January 17-20, 1998.
      Abstracts.

PMID- 11320978
TI  - APICON 2001. 56th Joint Annual Conference. New Delhi, India. January 20-24, 2001.
      Abstracts.

PMID- 11320976
TI  - IX International Symposium on Progress in Clinical Pacing. 5-8 December 2000,
      Rome, Italy. Abstracts.

PMID- 11320979
TI  - IV World Congress on Mountain Medicine and High Altitude Physiology. October 1-6,
      2000. Arica, Chile. Abstracts.

PMID- 11320980
TI  - [RNSA Days (National Aerobiology Surveillance Network). 1-2 December 2000. Part
      1].

PMID- 11320981
TI  - Factors modifying the effect of bystander cardiopulmonary resuscitation on
      survival in out-of-hospital cardiac arrest patients in Sweden.
AB  - AIM: To describe possible factors modifying the effect of bystander
      cardiopulmonary resuscitation on survival among patients suffering an out-of
      hospital cardiac arrest. PATIENTS: A national survey in Sweden among patients
      suffering out-of-hospital cardiac arrest and in whom resuscitative efforts were
      attempted. Sixty per cent of ambulance organizations were included. DESIGN:
      Prospective evaluation. Survival was defined as survival 1 month after cardiac
      arrest. RESULTS: In all, 14065 reports were included in the evaluation. Of these,
      resuscitation efforts were attempted in 10966 cases, of which 1089 were witnessed
      by ambulance crews. The report deals with the remaining 9877 patients, of whom
      bystander cardiopulmonary resuscitation was attempted in 36%. Survival to 1 month
      was 8.2% among patients who received bystander cardiopulmonary resuscitation vs
      2.5% among patients who did not receive it (odds ratio 3.5, 95% confidence
      interval 2.9-4.3). The effect of bystander cardiopulmonary resuscitation on
      survival was related to: (1) the interval between collapse and the start of
      bystander cardiopulmonary resuscitation (effect more marked in patients who
      experienced a short delay); (2) the quality of bystander cardiopulmonary
      resuscitation (effect more marked if both chest compressions and ventilation were
      performed than if either of them was performed alone); (3) the category of
      bystander (effect more marked if bystander cardiopulmonary resuscitation was
      performed by a non-layperson); (4) interval between collapse and arrival of the
      ambulance (effect more marked if this interval was prolonged); (5) age (effect
      more marked in bystander cardiopulmonary resuscitation among the elderly); and
      (6) the location of the arrest (effect more marked if the arrest took place
      outside the home). CONCLUSION: The effect of bystander cardiopulmonary
      resuscitation on survival after an out-of-hospital cardiac arrest can be modified
      by various factors. Factors that were associated with the effect of bystander
      cardiopulmonary resuscitation were the interval between the collapse and the
      start of bystander cardiopulmonary resuscitation, the quality of bystander
      cardiopulmonary resuscitation, whether or not the bystander was a layperson, the
      interval between collapse and the arrival of the ambulance, age and the place of
      arrest.

PMID- 11320982
TI  - Unusual appearance of an en plaque  meningioma of the cervical spinal canal.    
      A case report and literature review.
AB  - STUDY DESIGN: A case report of a patient with cervical spinal cord and nerve root
      compression caused by a meningioma en plaque together with calcification of the
      posterior longitudinal ligament is presented,with a review of the literature.
      OBJECTIVE: To present the diagnosis of a calcified dural meningioma en plaque,
      with extradural extension into the ligamentum flavum, in a woman with cervical
      myelopathy and neuropathy. SUMMARY OF BACKGROUND DATA: This case demonstrates
      that the cervical spine can be involved in dural meningioma en plaque with
      calcifications, in a manner mimicking ossification of the ligamentum flavum,
      which has never been previously reported. METHODS: A patient presenting with
      cervical cord and nerve root compression caused by ossification of the posterior
      longitudinal ligament and a concurrent calcified dural meningioma en plaque was
      treated surgically and has made a gradual recovery. Imaging studies,surgical
      findings, and histopathologic evaluation were analyzed to support the diagnosis.
      RESULTS: At surgery, ossification of the posterior longitudinal ligament was
      noted, along with a calcified lesion involving the posterior cervical dura and
      the adjacent ligamentum flavum. A calcified meningioma was diagnosed by
      histopathologic examination of the dural-based lesion. CONCLUSION: Although
      previously not described, the diagnosis of calcified dural meningioma en plaque
      should be considered in all patients presenting with spinal cord and/or nerve
      root compression,even at cervical levels. Although ossification of the posterior
      longitudinal ligament and ossification of the ligamentum flavum are more common
      etiologies of partially circumferential spinal calcification, dural-based
      meningiomas with extension into the surrounding ligaments demand early
      recognition because they can be associated with a poorer prognosis.

PMID- 11320983
TI  - Coexistence of thrombophilic gene polymorphisms among 559 unrelated consecutive
      patients with a history of thrombosis.

PMID- 11320984
TI  - Virchow's triad revisited: the importance of soluble coagulation factors, the
      endothelium, and platelets.

PMID- 11320985
TI  - [Obstetrical ultrasonography during pregnancy without risk factors].

PMID- 11320986
TI  - Joint meeting of Sicilia and Calabria-Basilicata-Puglia-Campania-Molise section,
      and neurochemistry, nucleotides and nucleic acids, marine and environmental
      biochemical groups. Catania, June 11-13, 1998. Abstracts.

PMID- 11320987
TI  - Fanconi anemia associated with increased nuchal translucency detected by first
      trimester ultrasound.
AB  - Increased nuchal translucency between 10 and 14 weeks of gestation has now been
      established as a marker for chromosomal defects in several large-scale studies.
      In addition, a growing number of structural defects and some rare genetic
      syndromes have been identified in association with this marker. We describe a
      case of a fetus with increased nuchal translucency at 12 weeks of gestation, in
      which second-trimester evaluation by ultrasound showed an enlarged cisterna
      magna, a ventricular septal defect and moderate signs of dysmorphia. Karyotyping
      by chorionic villus sampling revealed a high rate of chromosomal breaks. The
      diagnosis of Fanconi anemia with early onset was confirmed following the
      development of severe postnatal anemia 2 months after birth.

PMID- 11320988
TI  - Prenatal diagnosis of 13q- syndrome in a fetus with holoprosencephaly and thumb
      agenesis.
AB  - Partial deletion of the long arm of one of the chromosomes 13 is an exceedingly
      rare condition. We report such a case in a 32-week fetus presenting with
      polyhydramnios, growth restriction and multiple structural defects including
      alobar holoprosencephaly, facial abnormalities, clubfoot, clinodactyly and thumb
      agenesis. Fetal blood sampling revealed a 46,XY, del(13)(q22 --> qter) abnormal
      male karyotype. Postmortem examination confirmed the prenatal findings and showed
      other manifestations of the syndrome. To our knowledge, this case represents the
      first in which the prenatal ultrasound detection of holoprosencephaly in
      association with distal limb abnormalities led to the prenatal diagnosis of the
      13q- syndrome.

PMID- 11320989
TI  - Congenital lobar emphysema--the disappearing chest mass: antenatal ultrasound
      appearance.
AB  - Prenatal diagnosis of congenital lobar emphysema is rarely reported in the
      literature. This case presents a fetus with an echogenic lung diagnosed at 18
      weeks' gestation, that resolved completely during the pregnancy. This case is
      unique in that sonographic increased echogenicity was first noted at 18 weeks'
      gestation and had disappeared by 29 weeks' gestation. The diagnosis was made in
      the postnatal period as a result of follow up of the prenatal findings. This case
      reinforces the importance of continuing postnatal investigations of prenatal
      sonographic abnormalities even when they appear to have disappeared. A discussion
      of the causes of congenital lobar emphysema is presented.

PMID- 11320990
TI  - Investigational COX-2 inhibitor relieves pain in dental model.

PMID- 11320991
TI  - FDA approves shock wave device for treatment of chronic heel pain.

PMID- 11320992
TI  - Epidural corticosteroid injections most effective soon after symptom onset.

PMID- 11320993
TI  - Web alert.

PMID- 11320995
TI  - 9th International Symposium on Pediatric Neuro-Oncology. San Francisco,
      California, USA. June 11-14, 2000. Abstracts.

PMID- 11320994
TI  - 4th Congress of the European Association of Neuro-Oncology. Copenhagen, Denmark.
      June 3-6, 2000. Abstracts.

PMID- 11320997
TI  - Proceedings of the 15th International Conference on Oral Biology. June 28-July 1,
      1998. Baveno, Italy.

PMID- 11320996
TI  - Consultation section. Refractive surgical problem.

PMID- 11320998
TI  - Sylvester O'Halloran Surgical Scientific Meeting. March 9-10, 2001. Abstracts.

PMID- 11320999
TI  - [2nd National Meeting of Graduate Studies in Endocrinology-Diabetes. Nice,
      France, 14-16 December 2000].

PMID- 11321000
TI  - Increasing productivity and quality of care: robot-aided neuro-rehabilitation.
AB  - This paper presents an overview of our research in robot-aided stroke neuro
      rehabilitation and recovery. At the onset of this research we had to confront
      squarely (and solve!) a critical question: If anatomy is destiny, can we
      influence it? Our efforts over the last five years have been focused on answering
      this question and we will present a few of our clinical results from over 2,000
      hours of robot-aided therapy with 76 stroke patients. To determine if exercise
      therapy influences plasticity and recovery of the brain following a stroke, we
      needed the appropriate "microscope" that would allow us to concomitantly control
      the amount of therapy delivered to a patient, while objectively measuring
      patient's performance. Back-driveable robots are the key enabling technology. Our
      results to date using common clinical scales suggest that robot-aided
      sensorimotor training does have a genuinely positive effect on reduction of
      impairment and the reorganization of the adult brain. Yet while clinical scales
      can help us to examine the impact in the neuro-recovery process, their coarse
      nature requires extensive and time-consuming trials, and on top of that they fail
      to show us details important for optimizing therapy. Alternative, robot-based
      scales offer the potential benefit of new finer measurements-and deeper insight
      into the process of recovery from neurological injury. We also plan to use
      present technology to establish the practicality and economic feasibility of
      clinician-supervised, robot-administered therapy, including classroom therapy. We
      feel quite optimistic that the march of progress will accelerate substantially in
      the near future and allow us to transfer this technology from the research realm
      to the everyday treatment of stroke survivors.

PMID- 11321001
TI  - Understanding and treating arm movement impairment after chronic brain injury:
      progress with the ARM guide.
AB  - Significant potential exists for enhancing physical rehabilitation following
      neurologic injury through the use of robotic and mechatronic devices (or
      "rehabilitators"). We review the development of a rehabilitator (the "ARM Guide")
      to diagnose and treat arm movement impairment following stroke and other brain
      injuries. As a diagnostic tool, the ARM Guide provides a basis for evaluation of
      several key motor impairments, including abnormal tone, incoordination, and
      weakness. As a therapeutic tool, the device provides a means to implement and
      evaluate active assist therapy for the arm. Initial results with three stroke
      subjects demonstrate that such therapy can produce quantifiable benefits in the
      chronic hemiparetic arm. Directions for future research regarding the efficacy
      and practicality of rehabilitators are discussed.

PMID- 11321002
TI  - Development of robots for rehabilitation therapy: the Palo Alto VA/Stanford
      experience.
AB  - For over 25 years, personal assistant robots for severely disabled individuals
      have been in development. More recently, using robots to deliver rehabilitation
      therapy has been proposed. This paper summarizes the development and clinical
      testing of three mechatronic systems for post-stroke therapy conducted at the VA
      Palo Alto in collaboration with Stanford University. We describe the philosophy
      and experiences that guided their evolution. Unique to the Palo Alto approach is
      provision for bimanual, mirror-image, patient-controlled therapeutic exercise.
      Proof-of-concept was established with a 2-degree-of-freedom (DOF) elbow/forearm
      manipulator. Tests of a second-generation therapy robot producing planar forearm
      movements in 19 hemiplegic and control subjects confirmed the validity and
      reliability of interaction forces during mechanically assisted upper-limb
      movements. Clinical trials comparing 3-D robot-assisted therapy to traditional
      therapy in 21 chronic stroke subjects showed significant improvement in the Fugl
      Meyer (FM) measure of motor recovery in the robot group, which exceeded
      improvements in the control group.

PMID- 11321003
TI  - A body-powered functional upper limb orthosis.
AB  - This paper describes the development and preliminary testing of a functional
      upper-limb orthosis for people that have limited strength in their arms. This is
      symptomatic of conditions such as muscular dystrophy (MD), spinal muscular
      atrophy (SMA), and partial spinal cord injury. The exoskeletal orthosis is
      wheelchair mounted, has two links and four degrees of freedom. It uses linear
      elastic elements to balance out the effects of gravity in three dimensions.
      Preliminary results on testing with ten subjects will be presented.

PMID- 11321004
TI  - A multi-purpose rehabilitation frame: a novel apparatus for balance training
      during standing of neurologically impaired individuals.
AB  - We present a novel mechanical apparatus, named Multi-purpose Rehabilitation Frame
      (MRF), and methods for balance training during standing of neurologically
      impaired individuals. The device has two degrees of freedom (DOF), which allow
      for constrained movement of both lower limbs and pelvis in the sagittal and
      frontal planes. The MRF aims at improving balancing in impaired individuals by
      providing a stiffness support and action of perturbations, which facilitate
      development of alternative balancing strategies. The level of stiffness support
      and strength of perturbations, which are generated by means of two hydraulic
      servo-controlled actuators, can be selected according to current balancing
      abilities of an impaired individual. We further present preliminary results of
      nine days of balance training in two paraplegic and two incomplete tetraplegic
      subjects standing in the MRF. All subjects improved their balancing abilities as
      measured from the level of needed supporting stiffness provided by the MRF.

PMID- 11321005
TI  - Treadmill training of paraplegic patients using a robotic orthosis.
AB  - Recent studies have confirmed that regular treadmill training can improve walking
      capabilities in incomplete spinal cord-injured subjects. At the beginning of this
      training the leg movements of the patients have to be assisted by
      physiotherapists during gait on the moving treadmill. The physical capabilities
      and the individual experience of the therapists usually limit this training. A
      driven gait orthosis (DGO) has been developed that can move the legs of a patient
      in a physiological way on the moving treadmill. The orthosis is adjustable in
      size so different patients can use it. Actuators at the knee and hip joints are
      controlled by a position controller. With the DGO the legs of patients with
      different degrees of paresis and spasticity could be trained for more than half
      an hour, and physiological gait patterns were obtained.

PMID- 11321006
TI  - A mechanized gait trainer for restoration of gait.
AB  - The newly developed gait trainer allows wheel-chair-bound subjects the repetitive
      practice of a gait-like movement without overstressing therapists. The device
      simulates the phases of gait, supports the subjects according to their abilities,
      and controls the center of mass (CoM) in the vertical and horizontal directions.
      The patterns of sagittal lower limb joint kinematics and of muscle activation for
      a normal subject were similar when using the mechanized trainer and when walking
      on a treadmill. A non-ambulatory hemiparetic subject required little help from
      one therapist on the gait trainer, while two therapists were required to support
      treadmill walking. Gait movements on the trainer were highly symmetrical, impact
      free, and less spastic. The vertical displacement of the CoM was bi-phasic
      instead of mono-phasic during each gait cycle on the new device. Two cases of non
      ambulatory patients, who regained their walking ability after 4 weeks of daily
      training on the gait trainer, are reported.

PMID- 11321007
TI  - User involvement in the design and evaluation of a smart mobility aid.
AB  - This paper describes the design and evaluation of an innovative smart mobility
      aid for the frail visually impaired. The Personal Adaptive Mobility AID (PAM-AID)
      was developed to address the difficulties in personal mobility of the frail and
      elderly visually impaired. The paper provides an overview of the PAM-AID research
      at Trinity College and describes the evolutionary nature of the design process.
      Because there were no existing systems to guide its development, a series of
      prototypes was constructed and they were regularly evaluated in the field. This
      approach views potential users as vital contributing members of the design team
      and led to rapid and hopefully useful improvements in the design.

PMID- 11321008
TI  - Rehabilitation applications of robotic technology.

PMID- 11321009
TI  - Low vision and blindness October 1999.

PMID- 11321011
TI  - Medical software's free future. More and better programmers are needed.

PMID- 11321010
TI  - Medical software's free future. All software developed at public's expense should
      be licensed as open source.

PMID- 11321013
TI  - Distinguishing between partial seizures and panic attacks. Psychotic and
      behavioural symptoms are also common in elderly patients.

PMID- 11321014
TI  - Distinguishing between partial seizures and panic attacks. Epileptic panic
      attacks are not limited to adults.

PMID- 11321015
TI  - Delivering bad news. Receiving bad news will always be unpleasant.

PMID- 11321016
TI  - Delivering bad news. Not all surgeons can counsel, and fewer psychotherapists can
      operate.

PMID- 11321017
TI  - Delivering bad news. Communication skills must be part of medical education in
      all specialties.

PMID- 11321018
TI  - Empathy is important for enablement.

PMID- 11321019
TI  - Radiation dose from depleted uranium can now be measured.

PMID- 11321020
TI  - Most psychiatrists oppose plans for new mental health act.

PMID- 11321021
TI  - Fumonisins Risk Assessment Workshop. 10-12 January 2000. College Park, Maryland,
      USA. Proceedings and abstracts.

PMID- 11321022
TI  - Lou Gehrig's death.

PMID- 11321023
TI  - Proceedings of the International Symposium on low-digestible carbohydrates.
      University of Salford, United Kingdom, 24-25 June 1999.

PMID- 11321024
TI  - Tolerance to low-digestible carbohydrates: symptomatology and methods.
AB  - Low-digestible carbohydrates (LDCs) are incompletely or not absorbed in the small
      bowel and fermented in the colon. They are usually well tolerated but may also
      have some dose-related undesirable effects due to their natural osmotic potential
      and/or excessive fermentation: borborygmi, excessive flatus, bloating, abdominal
      cramps and eventually diarrhoea. There is an important intersubject variability
      in the tolerance to LDCs because of differences in absorption capacity, motility
      pattern, colonic response and intestinal sensitivity. There is also a great
      intrasubject variability, depending on the type of LDC, dosage and type of
      consumption. Absorption of LDC in the small intestine can be assessed using
      hydrogen breath test or intubation techniques or analysis of ileostomy effluents.
      Double-blind, placebo-controlled studies are required to assess the subjective
      symptoms of intolerance, and the experimental conditions may influence the
      results.

PMID- 11321025
TI  - Beneficial health effects of low-digestible carbohydrate consumption.
AB  - Low-digestible carbohydrates represent a class of enzyme-resistant saccharides
      that have specific effects on the human gastrointestinal tract. in the small
      bowel, they affect nutrient digestion and absorption, glucose and lipid
      metabolism and protect against known risk factors of cardiovascular disease. In
      the colon they are mainly degraded by anaerobic bacteria in a process called
      fermentation. As a consequence, faecal nitrogen excretion is enhanced, which is
      used clinically to prevent or treat hepatic encephalopathy. Low-digestible
      carbohydrates are trophic to the epithelia of the ileum and colon, which helps to
      avoid bacterial translocation. Short-chain fatty acids are important fermentation
      products and are evaluated as new therapeutics in acute colitis. They are
      considered in the primary prevention of colorectal cancer. The bifidogenic effect
      of fructo-oligosaccharides merits further attention, Unfermented carbohydrates
      increase faecal bulk and play a role in the treatment of chronic functional
      constipation, symptomatic diverticulosis and, possibly, the irritable bowel
      syndrome. In conclusion, low-digestible carbohydrates may play a role in the
      maintenance of human digestive health. However, the strength of evidence differs
      between disease entities.

PMID- 11321026
TI  - Non-polyol low-digestible carbohydrates: food applications and functional
      benefits.
AB  - Many LDCs currently on the market are not digested in the upper gastrointestinal
      tract and become fermented in the large intestine. They possess physiological
      benefits similar to those of dietary fibre. For some of these materials the
      fermentation process is highly specialised and leads to the selective stimulation
      and growth of beneficial gut bacteria, e.g. bifidobacteria. These materials are
      described as prebiotics, which are defined as nutrients fermented in the large
      bowel that favour the growth of desirable large bowel microflora. This activity
      has been demonstrated for inulin and oligofructose. Two other carbohydrates with
      low digestibility that offer desirable physiological properties are resistant
      starch (RS) and polydextrose (PD). These 'functional benefits have led to
      considerable interest from the food industry leading to the use of these
      ingredients in the development of new 'healthy' products. This paper describes
      the use of these materials in the development of 'healthy' products, some of
      their functional properties, and the benefits they confer on different food
      systems.

PMID- 11321027
TI  - Low-digestible carbohydrates: the regulatory framework.
AB  - Legislation is described that impacts on the use of low-digestible carbohydrates
      in foods. This includes controls on the use of these carbohydrates, mandatory
      labeling concerned with gastrointestinal effects, nutrition labeling, and
      nutrition and other claims. Regional differences in approach to legislation have
      led to inconsistencies in the information that must be provided to consumers,
      even for the same food products. Also, within regions, different regulations
      apply to food carbohydrates that may be classified similarly from the
      physiological perspective. Consistency of food labelling globally and in
      application to similar carbohydrates would benefit from greater attention to the
      underpinning science.

PMID- 11321028
TI  - Workshop: physiology and tolerance of LDCs.

PMID- 11321029
TI  - Workshop: consumption and consumer perceptions.

PMID- 11321030
TI  - Workshop: regulatory affairs.

PMID- 11321031
TI  - Tolerance of low-digestible carbohydrates: a general view.
AB  - The tolerance of low-digestible carbohydrates (LDCs) may be measured as the
      potential to cause abdominal symptoms and laxation. Tolerance of any one LDC is
      determined by its concentration in the food product eaten, the amount of the food
      product eaten, the frequency of eating the food and the consumption of other
      foods (increasing tolerance) and water decreasing tolerance). Added to these,
      individuals vary considerably in their response to low-digestible carbohydrates
      in the reporting of gastrointestinal symptoms. A precise maximum no-response dose
      is sometimes difficult to obtain because some dose--response curves are
      distinctly sigmoidal. Food regulators hoping to set a trigger level at which
      laxation may occur have been unable to take account of all these factors because
      the necessary information matrices are not available for any one LDC.
      Nevertheless analysis of the data shows consistent trends and for circumstances
      when food is consumed throughout the day it now seems feasible to assign specific
      tolerances to specific low-digestible carbohydrates, especially the polyols for
      which most is known. The method by which the no-effect dose or laxative threshold
      is expressed is critical to its application to individual foods.

PMID- 11321032
TI  - [Representation of women in German medical research. Editorial].

PMID- 11321033
TI  - Apoptosis in AIDS.
AB  - Infection with the human immunodeficiency virus type 1 (HIV-1) leads to
      progressive immunodeficiency and onset of opportunistic infections and neoplasms.
      The loss of immune competence is associated with declines in both the
      functionality and the number of CD4+ lymphocytes. Multiple mechanisms have been
      proposed to explain death and dysfunction of CD4+ T-cells. The mechanisms of HIV
      1-mediated cell death which are relevant in vivo are unclear at present. However,
      in vitro explorations on the cytopathic effects of HIV-1 have yielded a wealth of
      potential triggering events, and signaling and effector pathways leading to
      apoptosis. The types of pro- and anti-apoptotic stimuli that have been associated
      with HIV-1 are multiple and often appear overlapping or even contradictory. This
      review focuses on the various molecular determinants from HIV-1 that play a role
      in induction of apoptosis in T-lymphocytes. Special attention is devoted to the
      viral genes, env, nef, tat and vpr, for which a significant body of literature on
      apotosis-related effects is available.

PMID- 11321034
TI  - Will imaging of apoptosis play a role in clinical care? A tale of mice and men.
AB  - Programmed cell death (apoptosis) plays a role in the pathophysiology of many
      diseases and in the outcome of treatment. Apoptosis is the likely mechanism
      behind the cytoreductive effects of standard chemotherapeutic and radiation
      treatments, rejection of organ transplants, cellular damage in collagen vascular
      disorders, and delayed cell death due to hypoxic-ischemic injury in myocardial
      infarction and neonatal hypoxic ischemic injury. Observations about the role of
      apoptosis have fueled the development of novel agents and treatment strategies
      specifically aimed at inducing or inhibiting apoptosis. Despite these research
      developments there are no clinical entities where specific measures of apoptosis
      are used in either diagnosis or patient management. Part of the difficulty in
      bridging the gap between the basic science understanding of apoptosis and the
      clinical application of this information is the lack of a sensitive marker to
      monitor programmed cell death in association with disease progression or
      regression. Technetium-99m labeled annexin V localizes at sites of apoptosis in
      vivo, due to its nanomolar affinity for membrane bound phosphatidylserine.
      Radiolabeled annexin V imaging permits identification of the site and extent of
      apoptosis in experimental animals. Annexin V has been successfully used in animal
      models to image organ transplant rejection, characterize successful therapy of
      tumors, pinpoint acute myocardial infarction, and identify hypoxic ischemic brain
      injury of the newborn and adult. Early studies in human subjects suggest that
      99mTc annexin imaging will be also be useful to identify rejection in transplant
      recipients, localize acute myocardial infarction, and characterize the
      effectiveness of a single treatment in patients with tumors. This review
      describes the imaging approaches to detect and monitor apoptosis in-vivo that are
      presently in early clinical trials. The preliminary data are extrapolated to
      identify conditions where apoptosis imaging may be valuable in clinical decision
      making. These conditions include: transplant rejection; hypoxic/ischemic injury
      of heart and brain; and determining the efficacy of therapy in cancer, heart
      failure and osteoporosis.

PMID- 11321035
TI  - A concomitant ATP-depleting strategy markedly enhances anticancer agent activity.
AB  - Most anticancer agents effect DNA damage which initiate the cell death pathways
      of necrosis and apoptosis, but cancer cells of lesser sensitivity are only
      sublethally injured, and recover. The two death pathways and their
      interelationships in the presence of endogenous inhibitors of apoptosis and
      genetic deletions that facilitates only sublethal damage, are reviewed. Both ATP
      and pyrimidine levels in the sublethally injured cancer cells are reduced but not
      to low levels insuffient to sustain cell viability. However, this sublethal
      damage by the anticancer agent creates a therapeutic opportunity for further
      reduction of these key metabolites to lower levels that will not support life.
      Data in tumor-bearing animals is reviewed demonstrating that a combination of ATP
      depleting agents plus a de novo pyrimidine inhibitor (PALA) administered
      concomitantly with each of nine different anticancer agents markedly enhances
      tumor regression rates,and even produces some cures. It is necessary to deplete
      tumor ATP levels seveerely (>85%) by a combination of agents that block both
      synthesis (6-methylmercaptopurine riboside, a purine de novo synthesis inhibitor)
      and generation of ATP(6-aminonicotinamide, an inhibitor of glycolysis.) Cell
      viability cannot be sustained if the intracellular ATP level is reduced to 15% of
      normal or below. In vivo data employing this novel therapeutic strategy with
      cisplatin is presented. The potential significance of these findings to the
      improvement of cancer treatment is discussed.

PMID- 11321036
TI  - Inactivation of Myc-induced p53-dependent apoptosis in human tumors.
AB  - The Myc family of oncoproteins promote cell growth and are frequently
      overexpressed in human tumors. However, Myc can also trigger cell death by
      apoptosis. This is at least in part mediated via the ARF-p53 pathway. Myc
      activation leads to a selection for inactivation of ARF or p53, allowing cell
      survival and tumor progression. Restoration of p53-dependent apoptosis by various
      means is an attractive approach for new cancer therapy.

PMID- 11321037
TI  - Exploiting the apoptotic process for management of HIV: are we there yet?
AB  - CD4+ T cells die in individuals infected with HIV, either as a result of direct
      HIV infection or as uninfected "innocent bystanders". Possible mechanisms for
      bystander killing include generation of viral products such as Tat or gp120 and
      expression of death receptor ligands, such as FasL, that engage functional death
      receptors on uninfected cells. This review covers the sometimes conflicting in
      vitro and ex vivo studies that address these possible mechanisms of HIV
      associated cell death. It is an intriguing possibility that manipulation of cell
      death processes, to decrease bystander death or increase death of infected cells,
      in patients infected with HIV might provide a useful adjunct to antiretroviral
      therapy.

PMID- 11321038
TI  - Role of the newer p53 family proteins in malignancy.
AB  - The most recently identified members of the p53 family, p63 and p73, share
      certain structural and functional similarities with p53. Both p63 and p73 can
      bind to canonical p53-DNA-binding sites, transactivate the promoters of known p53
      target genes and induce apoptosis. Despite these similarities there are many
      important differences. In contrast to p53, p63 and p73 give rise to multiple
      distinct protein isoforms that have different functional properties. Upstream
      signaling pathways involved in the activation of p63 and p73 differ from those
      involved in p53 activation. Only a subset of the DNA damaging agents that induce
      p53 can induce p73. Cellular and viral oncoproteins can discriminate between p53
      and the newer family members. In addition, the levels of p63 and p73 are affected
      by certain states of cellular differentiation. Finally, it is becoming clear that
      the newest members of the p53 family are not classical tumor suppressor genes. In
      contrast to the high prevalence of p53 mutations in human cancers, p63 and p73
      mutations are rare. Indeed, levels of p73 increase during malignant progression.
      In addition, unlike p53-/- mice, mice lacking p63 and p73 do not develop tumors,
      but instead have significant developmental abnormalities. Mutations in p63 have
      also been detected in humans with the ectodermal dysplastic syndrome EEC. Further
      studies are required to determine whether qualitative or quantitative differences
      in the expression of p63 and p73 isoforms are important in the development of
      human cancers.

PMID- 11321039
TI  - Implications of altered apoptosis in diabetes mellitus and autoimmune disease.
AB  - Lymphocyte development, selection and education represent tightly controlled
      immune processes that normally prevent autoimmunity. Lymphocyte development
      requires cellular selection through apoptosis to remove potentially autoreactive
      cells. Dysregulated apoptosis, both interrupted as well as accetuated apoptosis,
      are now demonstrated as central defects in diverse human and murine autoimmune
      disease. In murine models of autoimmune lupus, mutations in cell death receptor
      CD95 (Fas) and its ligand CD95L (FasL) have been identified; these errors create
      a lymphoid system resistant to apoptosis. In contract, select lymphoid
      subpopulations of auto immune diabetic mice have accelerated apoptosis due to
      faulty activation of transcription factor NF-kappaB that normally protects
      against apoptotic death. The genetic basis of interrupted NF-kappaB in diabetes
      is a gene defect in an essential subunit of the proteasome. Although no specific
      gene in most common forms of human autoimmune disease has been identified,
      functional assays repeatedly demonstrate apoptotic defects in multiple cellular
      signaling pathways for cell death.

PMID- 11321041
TI  - Apoptosis in the eyes of a clinician.

PMID- 11321040
TI  - Apoptosis in multiple myeloma: therapeutic implications.
AB  - Apoptosis is the primary means by which most radio- and chemotherapy modalities
      kill cancer cells, and abnormalities in the apoptotic pathways may contribute to
      disease pathogenesis of cancer. Multiple Myeloma (MM) is a hematological
      malignancy which will affect 14,000 new individuals in the United States in 2001
      and remains irreversibly fatal despite all available therapies. The current
      review focuses on the studies of apoptotic and survival signaling pathways in MM
      cells, which have both identified novel apoptotic and anti-apoptotic proteins and
      provided targets for novel therapeutics.

PMID- 11321042
TI  - Novel vitamin K-dependent pathways regulating cell survival.
AB  - Historically, the vitamin K1-dependent proteins have been associated primarily
      with blood coagulation and secondarily with bone formation. Recent identification
      of K1-dependent proteins as specific ligands for the receptor tyrosine kinases
      (RTKs) that can stimulate cell replication and transformation and participate in
      cell survival highlighted a previously unrecognized and potentially important
      role for vitamin K1 in cell signaling. Growing evidence suggests that most normal
      and tumor cells possess an active K1-dependent gamma-carboxylation mechanism
      necessary for the production of gamma-carboxyglutamic acid (Gla)-containing
      proteins. Gla residues in proteins facilitate calcium-dependent
      protein/phospholipid interaction. Recent studies demonstrating the potentially
      positive effects of a vitamin K-dependent receptor:ligand system on cell growth
      and survival in general and the effects of the overexpression of these RTKs on
      malignant cell survival provide a new perspective on the role of vitamin K1, its
      dependent protein ligands, and their receptors. These cumulative observations
      also provide an explanation for the rigidly controlled K1 levels in the mammalian
      fetus and the minimal hepatic stores in the adult.

PMID- 11321043
TI  - Neurodegenerative disorders and ischemic brain diseases.
AB  - Degeneration and death of neurons is the fundamental process responsible for the
      clinical manifestations of many different neurological disorders of aging,
      incuding Alzheimer's disease, Parkinson's disease and stroke. The death of
      neurons in such disorders involves apoptotic biochemical cascades involving
      upstream effectors (Par-4, p53 and pro-apoptotic Bcl-2 family members),
      mitochondrial alterations and caspase activation. Both genetic and environmental
      factors, and the aging process itself, contribute to intiation of such neuronal
      apoptosis. For example, mutations in the amyloid precursor protein and presenilin
      genes can cause Alzheimer's disease, while head injury is a risk factor for both
      Alzheimer's and Parkinson's diseases. At the cellular level, neuronal apoptosis
      in neurodegenerative disorders may be triggered by oxidative stress, metabolic
      compromise and disruption of calcium homeostasis. Neuroprotective (antiapoptotic)
      signaling pathways involving neurotrophic factors, cytokines and "conditioning
      responses" can counteract the effects of aging and genetic predisposition in
      experimental models of neurodegenerative disorders. A better understanding of the
      molecular underpinnings of neuronal death is leading directly to novel
      preventative and therapeutic approaches to neurodegenerative disorders.

PMID- 11321044
TI  - The p53 tumor suppressor: critical regulator of life & death in cancer.
AB  - p53 is the most commonly mutated or deleted known gene in human cancer. The
      consequences of its disruption are profound, either in the germlines of patients
      with Li-Fraumeni Syndrome, or in mice with targeted gene knockouts. Abundant
      evidence suggests that p53 exerts regulation of cell cycle progression as well as
      apoptotic cell death, both in response to identical environmental or metabolic
      stressors. The specific decision of cell cycle arrest vs. death may underlie
      p53's differential ability to trigger death in cancer cells and arrest with
      repair in non-cancer cells, thus producing a therapeutic index pertinent to
      cancer therapy. Indeed, p53 status is likely to correlate with prognosis in many
      human cancers and in multiple animal tumor models. The mechanistic basis for
      p53's functions are still emerging, and will hopefully yield new therapeutic
      strategies applicable to treatment of the many poor-prognosis, p53-deficient
      human malignancies.

PMID- 11321045
TI  - Role of apoptosis of renal tubular cells in acute renal failure: therapeutic
      implications.
AB  - Acute renal failure (ARF) can be defined as a sudden loss of renal function and
      is a common and serious clinical problem. There are many causes of ARF but the
      most common cause results from injury to the renal tubular epithelial cells
      (RTECs). RTECs can be injured by schemia or by cytotoxic agents and, once
      injured, can die by necrosis or apotosis. In general, necrosis occurs in response
      to any severe injury, which leads to the biochemical collapse of the cell. Milder
      forms of the same types of injury cause apoptosis. At the cellular level there
      are fundamental differences between necrosis and apoptosis. Necrosis results from
      the additive effect of a number of independent biochemical events that are
      activated by severe depletion of cell energy stores. By contrast, apoptosis
      occurs via a coordinated, predictable and pre-determined pathway. These
      biochemical differences between apoptosis and necrosis have important therapeutic
      implications. Once a cell has been severely injured, necrosis is difficult to
      prevent. By contrast, the apoptotic pathway can potentially be modulated to
      maintain cell viability. The components of the apoptotic pathway that are
      potentially amenable to therapeutic modulation are discussed in detail in this
      review.

PMID- 11321046
TI  - Na+-dependent recovery of intracellular pH from acid loading in mouse colonic
      crypt cells.
AB  - The membrane transport mechanism for regulating the intracellular pH value (pHi)
      was investigated in mouse distal colon crypt cells. pHi was measured by
      microfluorometry in an isolated crypt fragment loaded with the pH-sensitive
      fluoroprobe, 2',7'-bis-(2-carboxyethyl)-5-(6) carboxyfluorescein. The pHi
      recovery process after acid loading induced by a 40 mM NH4Cl prepulse was almost
      totally dependent on Na+ in both the presence and absence of CO2/HCO3- in the
      perfusion solution. In the CO2/HCO3(-)-free, HEPES-buffered solution, amiloride
      partially inhibited the pHi recovery rate from acid loading with an ED50 value of
      15 microM and maximum inhibition of 83%. In a CO2/HCO3- solution, amiloride
      inhibited the pHi recovery rate with an ED50 value of 18 microM, which was
      similar to that in the HEPES-buffered solution, while the rate of pHi recovery
      remaining in the presence of the maximum effective concentration of amiloride was
      significantly larger than that in the HEPES-buffered solution. The Na+-dependent
      pHi recovery from the acid loading was significantly less (by 18%) in the
      presence of forskolin. These results suggest that the pHi recovery from acid
      loading was mediated by 1) amiloride-sensitive Na+/H+ exchanger, 2) the amiloride
      insensitive Na+/H+ exchanger, and 3) the Na+- and HCO3(-)-dependent acid
      extruder. The pHi recovery could be inhibited by cAMP.

PMID- 11321047
TI  - Involvement of granule-mediated apoptosis in the cyclic changes of the normal
      human endometrium.
AB  - Our objective is to investigate the involvement of granule-mediated apoptosis in
      the cyclic changes of the endometrium. We demonstrated the localization of CD56,
      perforin, granzyme B and caspase-3 in the endometrium by immunohistochemistry. We
      also confirmed the localization of perforin by immuno-electron microscopy, and
      demonstrated apoptosis in endometrial glandular cells by TdT-mediated dUTP-biotin
      nick end labeling (TUNEL) and electron microscopy. Uterine CD56-positive natural
      killer (NK) cells expressed perforin and granzyme B in its cytoplasm. Uterine NK
      cells increased significantly in the endometrial stroma during the secretory
      phase, and peaked during the late secretory phase. These cells started decreasing
      in number during the menstrual period. In endometrial glandular cells, caspase-3
      and TUNEL-positive cells increased significantly from the late secretory phase,
      with apoptosis reaching a peak during the menstrual period. Using electron
      microscopy, we observed uterine NK cells with chromatin rich, segmented nuclei
      and intracytoplasmic granules in the stroma obtained from late secretory phase
      endometria. These cells extended projections to the lining of endometrial
      glandular cells and attached to form a cell-to-cell contact. In addition, nuclear
      chromatin was observed to have already cohered and small cytoplasmic organelles
      were beginning to disappear, suggesting that these endometrial glandular cells
      were undergoing apoptosis. Utilizing immuno-electron microscopy, intracytoplasmic
      granules in uterine NK cells were stained with anti-perforin antibody. The
      findings of this study suggest that granule-mediated apoptosis in endometrial
      glandular cells induced by NK cells expressing perforin and granzyme B may be
      associated with the onset of menstruation.

PMID- 11321048
TI  - Changes in the tissue and plasma superoxide dismutase (SOD) levels in a burned
      rat model.
AB  - To examine whether thermal injury alters the superoxide dismutase (SOD)
      concentrations in various types of tissue or plasma, we studied the plasma and
      tissue Mn- and Cu/Zn-SOD levels in a rodent burn model. The animals were
      resuscitated with saline (50 mg/kg, i.p.) immediately following thermal injury
      and thereafter were sacrificed at either 6 or 24 hours post-burn. The Mn- and
      Cu/Zn-SOD levels were measured using an enzyme-linked immunosorbent assay
      (ELISA). The plasma Mn- and Cu/Zn-SOD concentrations significantly increased 6
      hours after the injury and positively correlated with the burn size. The kidney
      Mn-SOD concentrations were significantly higher 24 hours after the injury in the
      animals with 30% burns than in those with either sham or 50% burn injuries. The
      lung Cu/Zn-SOD concentrations were also significantly higher 6 hours after the
      injury in animals with 30% burns than in the other two types above. These
      findings suggest that the changes in the SOD concentrations after burn injury
      vary according to the type of SOD and also the type of tissue. As a result, the
      SOD concentrations may play some role in the early response to thermal trauma.

PMID- 11321049
TI  - In situ morphometric analysis of left and right ventricles in fetal rats: changes
      in ventricular volume, mass, wall thickness, and valvular size.
AB  - We studied morphological changes in the left and right ventricles of fetal rats
      in late-gestation using rapid whole-body freezing technique. Pregnant Wistar rats
      (term, 21.5 day) were immediately frozen in liquid nitrogen on 17-, 18-, 19-, 20
      , and 21-day of gestation. The frozen fetal hearts were serially sectioned with a
      sliding microtome and photographed. The ventricular volume, mass, wall thickness,
      and area of valvular orifice were measured on the photographs. During the study
      period, the left and right ventricular volumes increased very rapidly (9.9-fold
      and 7.6-fold, respectively) compared with the increase in the body weight (4.0
      fold); the volumes divided by body weight increased linearly. Left and right
      ventricular masses also rapidly increased (5.9-fold and 5.0-fold, respectively).
      Mass/volume ratios for the two ventricles rapidly decreased. The wall thicknesses
      divided by body weights rapidly decreased with the progression of the gestational
      age. The left and right ventricles at 17 day of gestation have relative
      hypertrophy and relatively large valvular orifices as compared with those in
      terminal gestation. The improvement of the relative hypertrophy of the ventricles
      may indicate the morphological and functional maturation of the fetal heart.

PMID- 11321050
TI  - Determination of optimal protein contents for a protein restriction diet in type
      2 diabetic patients with microalbuminuria.
AB  - To establish the method by which the optimal dietary protein content for type 2
      diabetic patients with nephropathy could be determined, dietary protein content
      was reduced in gradated steps and renal function was evaluated at the completion
      of each diet. Eight type 2 diabetic patients with microalbuminuria were examined
      in this study. Renal function, urinary albumin excretion rate (AER) and urinary
      excretion rates of prostaglandins were evaluated at the completion of each of
      three consecutive one-week dietary periods where the protein content was 1.2, 0.8
      and 0.6 g x kg Body Weight (BW)(-1) x day(-1) on the first, second and third
      week, respectively. Filtration fraction (FF), AER and urinary excretion rates of
      prostaglandin E2 and 6-keto-prostaglandin F1alpha significantly decreased in
      response to reduced dietary protein content from 1.2 to 0.8 g x kg BW(-1) x day(
      1). No additional decreases in FF, AER and urinary excretion rates of these two
      prostaglandins were obtained after the 0.6 g x kg BW(-1) x day(-1) low protein
      diet period. The method evaluating renal hemodynamics at the completion of
      several consecutive one-week dietary periods was confirmed to be useful to
      determine the optimal protein contents in type 2 diabetic patients with
      nephropathy. The result showed that the optimal protein content in type 2
      diabetic patients with microalbuminuria was 0.8 g x kg BW(-1) x day(-1) and
      protein restriction of less than 0.8 g x kg BW(-1) x day(-1) was not necessary
      for patients with this stage of diabetic nephropathy. A part of reasons in which
      FF decreased after reduced protein content in diet may be due to decreased
      prostaglandins production in the kidneys.

PMID- 11321051
TI  - Isolated and focal retrograde amnesia: a hiatus in the past.
AB  - Two cases of isolated retrograde amnesia were reported. Both showed the same
      clinical pattern in development and resolution of amnesia despite of different
      etiologies. Sudden insult to the brain (trauma in Case 1 and viral encephalitis
      in Case 2) caused concurrent antero- and retrograde amnesia. Fortunately both
      recovered from the anterograde amnesia completely. However, both were left with a
      period of postictal amnesia of a few months and retrograde amnesia of up to 14
      months' duration. The analysis of their pattern of temporal evolution and
      dissolution of amnesia support the hypothesis that recently acquired episodic
      information requires a certain amount of constant activation for a certain period
      of time in order to be organized into a durable memory. The nature of this
      activation as well as its origin remains to be solved.

PMID- 11321052
TI  - Marked improvement of neuropsychological impairment in a patient with chronic
      obstructive pulmonary disease after lung volume reduction surgery.
AB  - This paper reports a case of a 71-year-old pulmonary emphysema patient with
      neuropsychological impairments that were markedly improved 6 months after he
      underwent lung volume reduction surgery (LVRS). He also underwent pulmonary
      rehabilitation before and after surgery. He was suspected of having memory
      impairment and attention disorder when he was referred for rehabilitation. The
      neuropsychologic test showed a general cognitive impairment, attention disorder,
      and verbal memory impairment. Magnetic resonance imaging showed moderate atrophy
      of the left hippocampal area, cortex, and lacunae infarction in the
      periventricular area. Interestingly, scores of the neuropsychologic test, as well
      as severity of dyspnea and lung function, remarkably improved 6 months after
      LVRS. These results suggested that the neuropsychological impairments in
      pulmonary emphysema patients can be improved after lung reduction surgery.

PMID- 11321053
TI  - Thrombotic stroke in a child with diarrhea-associated hemolytic-uremic syndrome
      with a good recovery.
AB  - A boy aged 3.5 years with post-diarrheal hemolytic-uremic syndrome (HUS) was
      referred to our hospital because of convulsion and stupor. He had been admitted
      to a regional hospital with a 3-day history of bloody diarrhea, colic abdominal
      pain and fever. Two days later, he had complained of generalized seizures and
      oliguria. On admission, he developed anuria, and serum blood nitrogen and
      creatinine increased to 56 mg/100 ml and 2.8 mg/100 ml, respectively. Platelets
      decreased to 42,000/microl. Under the diagnosis of HUS, a continuous
      hemodiafiltration treatment had to be instituted. Computed tomography of his head
      at hospital day 5 revealed abnormal low density area of infarction with edema in
      both the basal ganglia involving with the posterior limb of internal capsule.
      Serum titer of IgM antibody to Escherichia coli O157 showed positive value.
      Although his anuria and stupor persisted over 10 days, he recovered without
      serious complications. These clinical observations may indicate that patients
      with similar lesions do not necessarily have serious morbidity.

PMID- 11321054
TI  - Environmental change and rates of evolution: the phylogeographic pattern within
      the hartebeest complex as related to climatic variation.
AB  - Global climate fluctuated considerably throughout the Pliocene-Pleistocene
      period, influencing the evolutionary history of a wide array of species. Using
      the phylogeographic patterns within the hartebeest (Alcelaphus buselaphus
      (Pallas, 1766)) complex, we evaluated the evolutionary consequences of such
      environmental change for a typical large mammal ranging on the African savannah.
      Our results, as generated from two mitochondrial DNA markers (the D-loop and
      cytochrome b), suggest an origin of the hartebeest in eastern Africa from where
      the species has colonized other parts of the continent. Phylogenetic analyses
      revealed an early diversification into southern and northern hartebeest lineages,
      an event that may be related to the formation of the Rift Valley lakes. The
      northern lineage has further diverged into eastern and western lineages, most
      probably as a result of the expanding central African rainforest belt and
      subsequent contraction of savannah habitats during a period of global warming.
      The diversification events appear to have coincided with major climatic changes
      and are highly correlated in time. These observations strongly suggest that large
      scale climatic fluctuations have been a major determinant for the species'
      evolutionary history and that hartebeest evolution has mainly taken place in
      isolated yet environmentally favourable refugia during periods of global warming.
      Indications of sudden population expansion for two putative ancestral hartebeest
      populations provide further support for a refugia-based explanation of the
      diversification events. Reciprocal monophyly between southern and northern
      lineages may suggest that reproductive barriers exist and that the hartebeest
      complex comprises two different species.

PMID- 11321055
TI  - The oldest fossil cichlids (Teleostei: Perciformes): indication of a 45 million
      year-old species flock.
AB  - Five closely related species of fossil cichlids collected from an Eocene site in
      Tanzania, East Africa, represent the oldest known cichlids. The specimens are
      whole-body, articulated fishes that are extremely well preserved and, therefore,
      have the potential to add to our knowledge of the history of this family. Modern
      cichlids are particularly well known for the numerous species flocks of the East
      African Great Lakes. A great deal of research is ongoing regarding all aspects of
      the fishes in these flocks, including their evolutionary history The new
      collection of fossils reported here is interpreted as representing a species
      flock that arose in a small crater lake. These fossils indicate that cichlids'
      ability to form species flocks evolved early in the history of this family.

PMID- 11321056
TI  - Phylogenetic relationships, historical biogeography and character evolution of
      fig-pollinating wasps.
AB  - Nucleotide sequences from the cytochrome oxidase I (COI) gene were used to
      reconstruct phylogenetic relationships among 15 genera of fig-pollinating wasps.
      We present evidence supporting broad-level co-cladogenesis with respect to most
      but not all of the corresponding groups of figs. Using fossil evidence for
      calibrating a molecular clock for these data, we estimated the origin of the fig
      wasp mutualism to have occurred ca. 90 million years ago. The estimated
      divergence times among the pollinator genera and their current geographical
      distributions corresponded well with several features of the break-up of the
      southern continents during the Late Cretaceous period. We then explored the
      evolutionary trajectories of two characteristics that hold profound consequences
      for both partners in the mutualism: the breeding system of the host (monoecious
      or dioecious) and pollination behaviour of the wasp (passive or active). The fig
      wasp mutualism exhibits extraordinarily long-term evolutionary stability despite
      clearly identifiable conflicts of interest between the interactors, which are
      reflected by the very distinct variations found on the basic mutualistic theme.

PMID- 11321057
TI  - Photopigments and colour vision in New World monkeys from the family Atelidae.
AB  - Most New World monkeys have an X-chromosome opsin gene polymorphism that produces
      a variety of different colour vision phenotypes. Howler monkeys (Alouatta), one
      of the four genera in the family Atelidae lack this polymorphism. Instead, they
      have acquired uniform trichromatic colour vision similar to that of Old World
      monkeys, apes and people through opsin gene duplication. In order to determine
      whether closely related monkeys share this arrangement, spectral sensitivity
      functions that allow inferences about cone pigments were measured for 56 monkeys
      from two other Atelid genera, spider monkeys (Ateles) and woolly monkeys
      (Lagothrix). Unlike howler monkeys, both spider and woolly monkeys are
      polymorphic for their middle- and long-wavelength cone photopigments. However,
      they also differ from other polymorphic New World monkeys in having two rather
      than three possible types of middle- and long-wavelength cone pigments. This
      feature directly influences the relative numbers of dichromatic and trichromatic
      monkeys.

PMID- 11321058
TI  - Matched filtering in motion detection and discrimination.
AB  - When humans detect and discriminate visual motion, some neural mechanism extracts
      the motion information that is embedded in the noisy spatio-temporal stimulus. We
      show that an ideal mechanism in a motion discrimination experiment cross
      correlates the received waveform with the signals to be discriminated. If the
      human visual system uses such a cross-correlator mechanism, discrimination
      performance should depend on the cross-correlation between the two signals.
      Manipulations of the signals' cross-correlation using differences in the speed
      and phase of moving gratings produced the predicted changes in the performance of
      human observers. The cross-correlator's motion performance improves linearly as
      contrast increases and human performance is similar. The ideal cross-correlator
      can be implemented by passing the stimulus through linear spatio-temporal filters
      matched to the signals. We propose that directionally selective simple cells in
      the striate cortex serve as matched filters during motion detection and
      discrimination.

PMID- 11321059
TI  - Reproductive performance links to fine-scale spatial patterns of female grey seal
      relatedness.
AB  - Fine-scale spatial patterns of female relatedness throughout the established grey
      seal breeding colony of North Rona, Scotland, were investigated by accurate
      mapping and spatially explicit analyses of a large sample (n = 262) of mothers
      using variation at nine microsatellite DNA loci. Local spatial autocorrelation
      analyses identified locations where seals were more highly related to the colony
      than average. These locations were also areas where the more successful females
      bred, were occupied first during each breeding season, were centrally placed
      locations of preferred habitat types and were likely to be the locations which
      were the first to be colonized historically. Mothers occupying such sites
      achieved higher than average pup growth rates, suggesting a founder fitness
      benefit.

PMID- 11321060
TI  - Patterns of sperm precedence and predictors of paternity in the Trinidadian
      guppy.
AB  - Despite its widespread occurrence in animals, sperm competition has been studied
      in a limited range of taxa. Among the most neglected groups in this respect are
      internally fertilizing fish in which virtually nothing is known about the
      dynamics of sperm competition. In this study, we examined the outcome of sperm
      competition when virgin female guppies mated with two males. Behavioural cues
      were used to ensure that each male mated once (with female cooperation) and that
      sperm were successfully inseminated at copulation. Two polymorphic microsatellite
      loci were used to estimate the proportion of offspring sired by the second male
      (P2) and the results revealed a bimodal distribution with either first or (more
      often) second male priority The observed P2 distribution differed from that
      expected under the 'fair raffle' model of sperm competition. Random sperm mixing
      is therefore unlikely to account for the observed variance in P2 in this study. A
      further aim of our study was to identify predictors of male reproductive success.
      Using logistic linear modelling, we found that the best predictors of paternity
      were time to remating and the difference in courtship display rate between first
      and second males. Males that mated quickly and performed relatively high numbers
      of sigmoid displays obtained greater parentage than their slower and less
      vigorous counterparts. Since females are attracted to high-displaying males, our
      results suggest that female choice may facilitate sperm competition and/or sperm
      choice in guppies.

PMID- 11321061
TI  - Selection on females can create 'larger males'.
AB  - In many bird and mammal species, males are significantly larger than females. The
      prevailing explanation for larger-sized males is that sexual selection drives
      increased male size. In addition, researchers commonly assume that the extent of
      dimorphism indicates the strength of selection for increased size in males. Here,
      through reconstruction of ancestral morphology for males and females of one large
      avian clade we present data that contradict this assumption and illustrate that
      selection for decreased female size explains 'male-biased' dimorphism ca. 50% of
      the time. Our findings are also inconsistent with ecological niche partitioning
      between the sexes and increased breeding benefits from reduced female size as
      general explanations for the evolution of size dimorphism within the clade. We
      conclude that it is incorrect to assume sexual dimorphism results from a single
      selective factor, such as directional sexual selection on increased male size.
      Rather, we suggest that the selective forces leading to sexual dimorphism may
      vary between species and should be tested on a case-by-case basis using a
      phylogenetic approach.

PMID- 11321062
TI  - Strategic male mating effort and cryptic male choice in a scorpionfly.
AB  - In animal species with high male mating effort, males often find themselves in a
      dilemma: by increasing their mating effort, the gain from each copulation
      increases but simultaneously reduces available resources and, thus, the
      opportunity for future copulations. Therefore, we expect males to spend less
      reproductive resources on matings that provide low reproductive potential,
      thereby saving resources for future copulations, possibly with high-quality
      females, a sort of cryptic male choice. However, the strength of the trade-off
      between investment in a current mating and resources available for future matings
      must not be the same for all males. Males with relatively high mating costs
      should allocate their limited resources more cautiously than males with more
      plentiful resources. Here, we examine this prediction in the scorpionfly Panorpa
      cognata. Prior to copulation, males produce a large salivary mass on which
      females feed during copulation. We show that the production of larger salivary
      masses leads to longer copulations. Moreover, the size of the salivary gland and
      salivary mass increases with increasing male condition. However, males in poor
      condition make a relatively higher mating investment than males in good
      condition. We therefore expect male condition to influence cryptic male choice.
      In accordance with our hypothesis, only males in poor condition choose
      cryptically, producing larger salivary masses in copulations with females of high
      fecundity.

PMID- 11321063
TI  - Intrasexual selection predicts the evolution of signal complexity in lizards.
AB  - Sexual selection has often been invoked in explaining extravagant morphological
      and behavioural adaptations that function to increase mating success. Much is
      known about the effects of intersexual selection, which operates through female
      mate choice, in shaping animal signals. The role of intrasexual selection has
      been less clear. We report on the first evidence for the coevolution of signal
      complexity and sexual size dimorphism (SSD), which is characteristically produced
      by high levels of male male competition. We used two complementary comparative
      methods in order to reveal that the use of complex signals is associated with SSD
      in extant species and that historical increases in complexity have occurred in
      regions of a phylogenetic tree characterized by high levels of pre-existing size
      dimorphism. We suggest that signal complexity has evolved in order to improve
      opponent assessment under conditions of high male male competition. Our findings
      suggest that intrasexual selection may play an important and previously
      underestimated role in the evolution of communicative systems.

PMID- 11321064
TI  - Evolution of cooperation through indirect reciprocity.
AB  - How can cooperation through indirect reciprocity evolve and what would it be
      like? This problem has previously been studied by simulating evolution in a small
      group of interacting individuals, assuming no gene flow between groups. In these
      simulations, certain 'image scoring' strategies were found to be the most
      successful. However, analytical arguments show that it would not be in an
      individual's interest to use these strategies. Starting with this puzzle, we
      investigate indirect reciprocity in simulations based on an island model. This
      has an advantage in that the role of genetic drift can be examined. Our results
      show that the image scoring strategies depend on very strong drift or a very
      small cost of giving help. As soon as these factors are absent, selection
      eliminates image scoring. We also consider other possibilities for the evolution
      of indirect reciprocity. In particular, we find that the strategy of aiming for
      'good standing' has superior properties. It can be an evolutionarily stable
      strategy and, even if not, it usually beats image scoring. Furthermore, by
      introducing quality variation among individuals into the model, we show that the
      standing strategy can be quality revealing, adding a new dimension to indirect
      reciprocity. Finally, we discuss general problems with currently popular
      modelling styles.

PMID- 11321065
TI  - Evolution of pathogen virulence: the role of variation in host phenotype.
AB  - Selection on pathogens tends to favour the evolution of growth and reproductive
      rates and a concomitant level of virulence (damage done to the host) that
      maximizes pathogen fitness. Yet, because hosts often pose varying selective
      environments to pathogens, one level of virulence may not be appropriate for all
      host types. Indeed, if a level of virulence confers high fitness to the pathogen
      in one host phenotype but low fitness in another host phenotype, alternative
      virulence strategies may be maintained in the pathogen population. Such
      strategies can occur either as polymorphism, where different strains of pathogen
      evolve specialized virulence strategies in different host phenotypes or as
      polyphenism, where pathogens facultatively express alternative virulence
      strategies depending on host phenotype. Polymorphism potentially leads to
      specialist pathogens capable of infecting a limited range of host phenotypes,
      whereas polyphenism potentially leads to generalist pathogens capable of
      infecting a wider range of hosts. Evaluating how variation among hosts affects
      virulence evolution can provide insight into pathogen diversity and is critical
      in determining how host pathogen interactions affect the phenotypic evolution of
      both hosts and pathogens.

PMID- 11321066
TI  - Fundamental clusters in spatial 2x2 games.
AB  - The notion of fundamental clusters is introduced, serving as a rule of thumb to
      characterize the statistical properties of the complex behaviour of cellular
      automata such as spatial 2 x 2 games. They represent the smallest cluster size
      determining the fate of the entire system. Checking simple growth criteria allows
      us to decide whether the cluster-individuals, e.g. some mutant family, are
      capable of surviving and invading a resident population. In biology, spatial 2 x
      2 games have a broad spectrum of applications ranging from the evolution of
      cooperation and intraspecies competition to disease spread. This methodological
      study allows simple classifications and long-term predictions in various
      biological and social models to be made. For minimal neighbourhood types, we show
      that the intuitive candidate, a 3 x 3 cluster, turns out to be fundamental with
      certain weak limitations for the Moore neighbourhood but not for the Von Neumann
      neighbourhood. However, in the latter case, 2 x 2 clusters generally serve as
      reliable indicators to whether a strategy survives. Stochasticity is added to
      investigate the effects of varying fractions of one strategy present at
      initialization time and to discuss the rich dynamic properties in greater detail.
      Finally, we derive Liapunov exponents for the system and show that chaos reigns
      in a small region where the two strategies coexist in dynamical equilibrium.

PMID- 11321067
TI  - Geometrical and crystallographic constraints determine the self-organization of
      shell microstructures in Unionidae (Bivalvia: Mollusca).
AB  - Unionid shells are characterized by an outer aragonitic prismatic layer and an
      inner nacreous layer. The prisms of the outer shell layer are composed of single
      crystal fibres radiating from spheruliths. During prism development, fibres
      progressively recline to the growth front. There is competition between prisms,
      leading to the selection of bigger, evenly sized prisms. A new model explains
      this competition process between prisms, using fibres as elementary units of
      competition. Scanning electron microscopy and X-ray texture analysis show that,
      during prism growth, fibres become progressively orientated with their three
      crystallographic axes aligned, which results from geometric constraints and space
      limitations. Interestingly transition to the nacreous layer does not occur until
      a high degree of orientation of fibres is attained. There is no selection of
      crystal orientation in the nacreous layer and, as a result, the preferential
      orientation of crystals deteriorates. Deterioration of crystal orientation is
      most probably due to accumulation of errors as the epitaxial growth is suppressed
      by thick or continuous organic coats on some nacre crystals. In conclusion, the
      microstructural arrangement of the unionid shell is, to a large extent, self
      organized with the main constraints being crystallographic and geometrical laws.

PMID- 11321068
TI  - Validation of publication of new names and new combinations previously
      effectively published outside the IJSEM.

PMID- 11321069
TI  - Notification that new names and new combinations have appeared in volume 50, part
      6, of the IJSEM.

PMID- 11321070
TI  - Notification that new names and new combinations have appeared in volume 51, part
      1, of the IJSEM.

PMID- 11321071
TI  - Burkholderia cepacia genomovar VI, a new member of the Burkholderia cepacia
      complex isolated from cystic fibrosis patients.
AB  - A polyphasic taxonomic study was performed on 23 strains isolated from cystic
      fibrosis (CF) patients in the USA. These strains were tentatively identified as
      Burkholderia cepacia, Burkholderia vietnamiensis and Burkholderia or Ralstonia
      sp. using biochemical tests and 16S rDNA-based PCR assays. Visual comparison of
      protein profiles indicated that they belonged to a single new group ('group 13').
      The polyphasic taxonomic data showed that 18 of these strains represent a new
      member of the B. cepacia complex, referred to in this report as B. cepacia
      genomovar VI, whereas the other five strains belonged to Burkholderia
      multivorans. By means of biochemical tests, B. cepacia genomovar VI strains can
      be separated from B. cepacia genomovars I and III, Burkholderia stabilis, B.
      vietnamiensis and Burkholderia gladioli, but not from B. multivorans. Separation
      of B. cepacia genomovar VI and B. multivorans is possible using AFLP (amplified
      fragment length polymorphism) fingerprinting and DNA-DNA hybridizations.
      Retrospective analysis of epidemiological and genotypic data suggests that
      strains of B. cepacia genomovar VI have been involved in chronic colonization of
      CF patients and have been spread from person to person.

PMID- 11321072
TI  - Proposal of Sphingomonas wittichii sp. nov. for strain RW1T, known as a dibenzo-p
      dioxin metabolizer.
AB  - A polyphasic taxonomic study was performed on Sphingomonas sp. strain RW1T. The
      organism was isolated from water of the River Elbe and has been known as a potent
      metabolizer of dibenzo-p-dioxin and its relatives. TLC of a mild alkaline
      hydrolysate of extractable cellular lipids of strain RW1T and type strains of 21
      Sphingomonas species gave a spot of sphingoglycolipid (SGL)-1 (glucuronosyl
      ceramide), which is characteristic of sphingomonads. In addition, strain RW1T and
      type strains of three Sphingomonas species (Sphingomonas yanoikuyae, Sphingomonas
      terrae and Sphingomonas macrogoltabidus) showed a second spot of SGL (SGL-1')
      identified as galacturonosyl ceramide. The presence of SGL-1 in cellular lipids
      suggested that strain RW1T is a member of the genus Sphingomonas. DNA-DNA
      reassociation rates between strain RW1T and each type strain of 14 Sphingomonas
      species including Sphingomonas paucimobilis, type species for the genus, revealed
      that strain RW1T is independent from these species. Results of phylogenetic
      analysis of 16S rDNA sequences of strain RW1T and type strains of 21 named
      Sphingomonas species verified that strain RW1T belongs to the genus Sphingomonas.
      Strain RW1T could be differentiated from named species of the genus by phenotypic
      characteristics and has been assigned to a new species, Sphingomonas wittichii
      sp. nov. The type strain is DSM 6014T (= JCM 10273T = EY 4224T). DNA G+C content
      is 67 mol %.

PMID- 11321073
TI  - Characterization of two novel saccharolytic, anaerobic thermophiles,
      Thermoanaerobacterium polysaccharolyticum sp. nov. and Thermoanaerobacterium zeae
      sp. nov., and emendation of the genus Thermoanaerobacterium.
AB  - Two anaerobic, thermophilic, Gram-positive, non-spore forming bacteria with an
      array of polysaccharide-degrading enzymes were isolated from the leachate of a
      waste pile from a canning factory in Hoopeston, East Central Illinois, USA. The
      results of 16S rDNA sequence homology indicated that their closest relatives
      belong to the saccharolytic, thermophilic and anaerobic genera of
      Thermoanaerobacterium and Thermoanaerobacter. Although, the evolutionary
      distances between these bacteria and their closest relatives are greater than
      11%, there is no defining phenotypic characteristic for the creation of a new
      genus. It is proposed that these bacteria should be placed in the genus
      Thermoanaerobacterium, which requires emendment of the genus description with
      regard to the reduction of thiosulfate to sulfur, because neither isolate is
      capable of this reduction. Thermoanaerobacterium polysaccharolyticum reduces
      thiosulfate to sulfide, whereas Thermoanaerobacterium zeae is unable to reduce
      thiosulfate. The cells of both isolates are rod-shaped and exist as single cells
      or sometimes in pairs. Cells are motile by means of flagella. Growth occurs
      between 45 and 72 degrees C, with optimum temperature of 65-68 degrees C at pH
      6.8. The pH range for growth is from 4 to 8 at a temperature of 65 degrees C.
      Both organisms ferment glucose, arabinose, maltose, mannose, rhamnose, sucrose,
      trehalose, xylose, cellobiose, raffinose, melibiose and melezitose. The major end
      products of fermentation with glucose are ethanol and CO2, with lesser amounts of
      acetate, formate, lactate and hydrogen. The DNA G+C contents of
      Thermoanaerobacterium polysaccharolyticum sp. nov. and Thermoanaerobacterium zeae
      sp. nov. are 46 and 42 mol%, respectively. The type strains are KMTHCJT (= ATCC
      BAA-17T = DSM 13641T) and mel2T (= ATCC BAA-16T = DSM 13642T), respectively.

PMID- 11321074
TI  - Pyrobaculum oguniense sp. nov., a novel facultatively aerobic and
      hyperthermophilic archaeon growing at up to 97 degrees C.
AB  - A novel hyperthermophilic, heterotrophic, rod-shaped archaeon was isolated from a
      terrestrial hot spring at Oguni-cho, Kumamoto Prefecture, Japan. The new isolate,
      strain TE7T, grew under aerobic, microaerobic and anaerobic conditions. Isolate
      TE7T grew optimally at 90-94 degrees C and pH 7.0-7.5 (adjusted at 25 degrees C)
      under atmospheric air with vigorous shaking. Strain TE7T cells were motile rods 2
      10 microm in length and covered with a surface-layer lattice. Cell yields at 90
      degrees C under aerobic conditions were twice that under anaerobic conditions.
      Under aerobic conditions, growth was inhibited by elemental sulfur, but
      thiosulfate stimulated growth. Under anaerobic conditions, no growth was observed
      in the presence of nitrate and nitrite, but elemental sulfur, thiosulfate, L
      cystine and oxidized glutathione stimulated growth. The 16S rDNA sequence of TE7T
      exhibited a close relationship to the sequences of Pyrobaculum aerophilum and
      Thermoproteus neutrophilus, which belong to the cluster of the genus Pyrobaculum.
      DNA-DNA hybridization analysis showed a low level of DNA similarity between TE7T
      and previously described Pyrobaculum species. As TE7T is phenotypically and
      phylogenetically different from the other members of this genus, it is described
      as a new species named Pyrobaculum oguniense (type strain TE7T = JCM 10595T = DSM
      13380T).

PMID- 11321075
TI  - Phylogenetic relationships of Xylella fastidiosa strains from different hosts,
      based on 16S rDNA and 16S-23S intergenic spacer sequences.
AB  - The phylogenetic relationships of Xylella fastidiosa strains isolated from
      different hosts, including citrus trees, coffee, grapevine, plum and pear, were
      inferred by sequence analysis of the 16S rDNA and 16S-23S intergenic spacer
      region. A high level of similarity (97.1-100%) was found in the 16S rDNA of the
      Xylella fastidiosa strains. The 16S-23S region showed a higher level of
      variation, with similarity values ranging from 79.8 to 100%. Two tRNAs (tRNA(Ala)
      and tRNA(Ile)) were encountered within the spacer sequence. The phylogenetic
      trees, constructed using the neighbour-joining method, showed that the citrus,
      coffee, peach and plum strains were closely related and separate from grapevine
      strains. The pear strain remained isolated from all the other Xylella strains in
      both analyses and produced values of less than 20% in DNA-DNA hybridization
      experiments with a citrus strain. These results show that this strain does not
      belong to the Xylella fastidiosa genomic species.

PMID- 11321076
TI  - Saccharopolyspora flava sp. nov. and Saccharopolyspora thermophila sp.nov., novel
      actinomycetes from soil.
AB  - The generic position of two aerobic, Gram-positive, non-acid-alcohol-fast
      actinomycetes was established following the isolation of their PCR-amplified 16S
      rRNA genes and alignment of the resultant sequences with the corresponding
      sequences from representatives of the families Actinosynnemataceae and
      Pseudonocardiaceae. The assignment of the organisms to the genus
      Saccharopolyspora was strongly supported by chemotaxonomic and morphological
      data. The strains were distinguished both from one another and from
      representatives of validly described Saccharopolyspora species on the basis of a
      number of phenotypic properties. It is proposed that the organisms, strains 07T
      (= AS4.1520T = IFO 16345T = JCM 10665T) and 216T (= AS4.1511T = IFO 16346T = JCM
      10664T), be classified in the genus Saccharopolyspora as Saccharopolyspora flava
      sp. nov. and Saccharopolyspora thermophila sp. nov., respectively.

PMID- 11321077
TI  - Dethiosulfovibrio russensis sp. nov., Dethosulfovibrio marinus sp. nov. and
      Dethosulfovibrio acidaminovorans sp. nov., novel anaerobic, thiosulfate- and
      sulfur-reducing bacteria isolated from 'Thiodendron' sulfur mats in different
      saline environments.
AB  - Four strains of strictly anaerobic, sulfur- and thiosulfate-reducing bacteria,
      SR12T, SR13, SR15T and WS100T, were isolated from 'Thiodendron' sulfur mats
      obtained from different saline environments. All isolates were motile, Gram
      negative, non-spore-forming curved rods with pointed or rounded ends. The sizes
      of cells varied from 0.9 x 3-5 microm for strains SR12T, SR13 and SR15T to 0.9 x
      4.8 microm for strain WS100T. All strains could form long spiral filamentous
      cells up to 70-110 microm during the early stage of growth. All strains were
      motile by a tumbling movement and possessed lateral flagella arranged at the
      concave side of cells. Incomplete cross-septa were distinctive features of all
      strains. Growth occurred at temperatures of 10-40 degrees C with an optimum at 28
      degrees C. The pH limits for growth were 5.5 to 8.0, with optimal growth at pH
      6.5-7.0. All isolates were obligately anaerobic and slightly halophilic and grew
      in media containing 0.5-5% NaCl with an optimum at 2% NaCl. All strains were
      chemoorganoheterotrophic, having a fermentative type of metabolism and utilized
      proteins, peptides, amino acids and some organic acids, but not sugars, fatty
      acids or alcohols. Some organic substrates (isoleucine, valine, alanine,
      glutamate) were utilized only by strain SR12T in the presence of sulfur or
      thiosulfate. Fermentation of citrate yielded mainly acetate, CO2 and H2. Sulfur
      and thiosulfate were reduced to hydrogen sulfide during the fermentation of
      organic substances, which increased cell yields and growth rates. Sulfate,
      sulfite, fumarate, nitrate, Fe2O3, MnO2, DMSO and elemental selenium were not
      used as electron acceptors by these strains. The G+C contents of the DNA were 51
      mol% for strains SR12T, SR13 and SR15T and 52 mol% for strain WS100T. Based on
      morphological, physiological and phylogenetic similarities, all four isolates
      could be assigned to three new species of the genus Dethiosulfovibrio, named
      Dethiosulfovibrio russensis (type strain DSM 12538T), Dethiosulfovibrio marinus
      (type strain DSM 12537T) and Dethiosulfovibrio acidaminovorans (type strain DSM
      12590T).

PMID- 11321078
TI  - Rickettsia felis: molecular characterization of a new member of the spotted fever
      group.
AB  - In this report, placement of Rickettsia felis in the spotted fever group (SFG)
      rather than the typhus group (TG) of Rickettsia is proposed. The organism, which
      was first observed in cat fleas (Ctenocephalides felis) by electron microscopy,
      has not yet been reported to have been cultivated reproducibly, thereby limiting
      the standard rickettsial typing by serological means. To overcome this challenge,
      several genes were selected as targets to be utilized for the classification of
      R. felis. DNA from cat fleas naturally infected with R. felis was amplified by
      PCR utilizing primer sets specific for the 190 kDa surface antigen (rOmpA) and 17
      kDa antigen genes. The entire 5,513 bp rompA gene was sequenced, characterized
      and found to have several unique features when compared to the rompA genes of
      other Rickettsia. Phylogenetic analysis of the partial sequence of the 17 kDa
      antigen gene indicated that R. felis is less divergent from the SFG rickettsiae
      than from the TG rickettsiae. The data corroborate results from previous reports
      that analysed the citrate synthase, 16S rRNA, rompB (135 kDa surface antigen),
      metK, ftsY, polA and dnaE genes that placed R. felis as a member of the SFG. The
      organism is passed trans-stadially and transovarially, and infection in the cat
      flea has been observed in the midgut, tracheal matrix, muscle, hypodermis,
      ovaries and testes.

PMID- 11321079
TI  - Pseudomonas alcaliphila sp. nov., a novel facultatively psychrophilic alkaliphile
      isolated from seawater.
AB  - Facultatively psychrophilic alkaliphilic strains were isolated from seawater
      obtained off the coast of Rumoi, Hokkaido, Japan. They were Gram-negative,
      aerobic straight rods with polar flagella. The isolates were catalase- and
      oxidase-positive and able to grow at 4 degrees C, but not at 40 degrees C. They
      produced acid from D-glucose under aerobic conditions. The isolates reduced
      nitrate to nitrite and hydrolysed casein and gelatin, but not starch or DNA. NaCl
      was required for growth at pH 10 but was not required at neutral pH. The major
      isoprenoid quinone was ubiquinone-9 (Q-9) and the DNA G+C content was 62.3-63.2
      mol%. The whole-cell fatty acids mainly consisted of C16:0, C16:1(9c) and
      C18:1(9c), with 3-OH C10:0 and 3-OH C12:0 as the hydroxyl fatty acids. A larger
      amount of trans-unsaturated fatty acid, C16:1(9t) was observed when the cells
      were grown at pH 7 compared to when cells were grown at pH 10. Phylogenetic
      analysis based on 16S rRNA gene sequencing indicated that the bacteria are
      members of the genus Pseudomonas. Analysis of DNA-DNA relatedness data with
      several close phylogenetic neighbours revealed a low level of hybridization (less
      than 61%). On the basis of phenotypic characteristics, phylogenetic analysis and
      DNA-DNA relatedness data, it is concluded that these isolates represent a
      separate new species. Accordingly, the name Pseudomonas alcaliphila is proposed.
      The type strain is AL15-21T (= JCM 10630T = IAM 14884T).

PMID- 11321080
TI  - Streptimonospora salina gen. nov., sp. nov., a new member of the family
      Nocardiopsaceae.
AB  - Actinomycete strain YIM 90002T (= CCTCC 99003T = CCRC 16284T) was isolated from a
      soil sample collected from a salt lake in the west of China. The aerial mycelium
      of this organism is well developed but not fragmented and, at maturity, forms
      short chains of spores. Spores in short chains are oval- to rod-shaped and have
      wrinkled surfaces. Substrate mycelium is branched with non-fragmenting hyphae and
      forms single oval to round spores borne on sporophores or dichotomously branching
      sporophores. Single spores have wrinkled surfaces. Single spores and spores in
      short chains are non-motile. Strain YIM 90002T contains meso-diaminopimelic acid,
      DD-diaminopimelic acid, glycine, lysine and aspartic acid in its cell wall and
      has glucose, galactose, ribose, xylose, arabinose and mannose as whole-cell
      sugars (no diagnostic sugars). The phospholipids are phosphatidylglycerol,
      phosphatidylinositol and phosphatidylethanolamine. The major menaquinones are MK
      9(H6), MK-10(H2) and MK-10(H4). Phylogenetic data indicate that this strain
      belongs to the family Nocardiopsaceae. The morphological and physiological
      characteristics and chemotaxonomic and phylogenetic data for this strain differ
      from those of previously described actinomycetes. Therefore, a new genus,
      Streptimonospora, is proposed for this organism; the type species of the genus is
      Streptimonospora salina gen. nov., sp. nov., and the type strain of S. salina is
      strain YIM 90002T.

PMID- 11321081
TI  - Desulfomonile limimaris sp. nov., an anaerobic dehalogenating bacterium from
      marine sediments.
AB  - Strains DCB-MT and DCB-F were isolated from anaerobic 3-chlorobenzoate (3CB)
      mineralizing cultures enriched from marine sediments. The isolates are large,
      Gram-negative rods with a collar girdling each cell. The isolates are obligate
      anaerobes capable of reductive dechlorination of 3CB to benzoate. Growth by
      chlororespiration in strain DCB-MT yielded 1.7 g protein mol(-1) 3CB
      dechlorinated with lactate as the electron donor. Strain DCB-MT also used
      fumarate, sulfate, sulfite, thiosulfate and nitrate as physiological electron
      acceptors for growth, but grew poorly on sulfate and nitrate. Reductive
      dechlorination was inhibited completely by sulfite and thiosulfate but not by
      sulfate. Both strains were incapable of growth at NaCl concentrations below 0.32%
      (w/v). They grew well at sea-water salt concentrations; however, the optimum
      growth rate was achieved at a NaCl concentration half that of sea water. The 16S
      rDNA sequence analysis shows strains DCB-MT and DCB-F to be 99% similar to each
      other and 93% similar to their closest relative, Desulfomonile tiedjei strain DCB
      1T. Strain DCB-MT can also be distinguished from strain DCB-1T by its inability
      to use acetate for growth on 3CB and by its requirement for NaCl. The morphology,
      physiology and 16S rDNA sequences of DCB-MT and DCB-F suggest that these strains
      represent a new, marine-adapted species of the genus Desulfomonile, designated
      Desulfomonile limimaris sp. nov. The type strain is strain DCB-MT (= ATCC
      700979T).

PMID- 11321082
TI  - Clarification of the relationship between the members of the family
      Thermomonosporaceae on the basis of 16S rDNA, 16S-23S rRNA internal transcribed
      spacer and 23S rDNA sequences and chemotaxonomic analyses.
AB  - To resolve relationships between members of the family Thermomonosporaceae,
      phylogenetic analyses using three sets of nucleotide sequences from 16S rDNA, 23S
      rDNA and the 16S-23S internal transcribed spacer (ITS) were carried out. Nearly
      all species of the family were included in this study. On the basis of congruous
      phylogenetic results and chemotaxonomic data, the following proposals are made.
      First, Actinomadura libanotica, Actinomadura aurantiaca, Actinomadura glomerata
      and Actinomadura longicatena are transferred to the genus Actinocorallia as
      Actinocorallia libanotica comb. nov., Actinocorallia aurantiaca comb. nov.,
      Actinocorallia glomerata comb. nov. and Actinocorallia longicatena comb. nov.,
      respectively. All the species of this genus are phylogenetically coherent and of
      phospholipid type PII (presence of phosphatidylethanolamine), distinguishing them
      from other Actinomadura species that are of phospholipid type PI (absence of
      diagnostic phospholipids). Second, Excellospora viridilutea is transferred to the
      genus Actinomadura as Actinomadura viridilutea comb. nov. As a result of the
      proposed transfers, the family Thermomonosporaceae now contains four genera
      Thermomonospora, Actinomadura, Actinocorallia and Spirillospora. The genus
      Actinocorallia and family Thermomonosporaceae are redescribed.

PMID- 11321083
TI  - A multiple-outgroup approach to resolving division-level phylogenetic
      relationships using 16S rDNA data.
AB  - The 16S rRNA gene (16S rDNA) is currently the most widely used gene for
      estimating the evolutionary history of prokaryotes. To date, there are more than
      30,000 16S rDNA sequences available from the core databases, GenBank, EMBL and
      DDBJ. This great number may cause a dilemma when composing datasets for
      phylogenetic analysis, since the choice and number of reference organisms are
      known to affect the resulting tree topology. A group of sequences appearing
      monophyletic in one dataset may not be so in another. This can be especially
      problematic when establishing the relationships of distantly related sequences at
      the division (phylum) level. In this study, a multiple-outgroup approach to
      resolving division-level phylogenetic relationships is suggested using 16S rDNA
      data. The approach is illustrated by two case studies concerning the monophyly of
      two recently proposed bacterial divisions, OP9 and OP10.

PMID- 11321084
TI  - Enterococcus villorum sp. nov., an enteroadherent bacterium associated with
      diarrhoea in piglets.
AB  - The taxonomic positions of five enteroadherent bacterial pig isolates, showing
      phenotypic characteristics most similar to those of Enterococcus durans and
      Enterococcus hirae, were investigated in a polyphasic study that included 16S
      rDNA sequence analysis, DNA-DNA hybridizations, DNA base-ratio determinations,
      whole-cell protein fingerprinting, D11344-primed PCR typing and an extensive
      examination of phenotypic properties. The results demonstrated that the organisms
      represent a new species in the Enterococcus faecium species group, for which the
      name Enterococcus villorum sp. nov. is proposed. The type strain is LMG 12287T (=
      CCM 4887T).

PMID- 11321085
TI  - Schineria larvae gen. nov., sp. nov., isolated from the 1st and 2nd larval stages
      of Wohlfahrtia magnifica (Diptera: Sarcophagidae).
AB  - Four bacterial strains were isolated from the fly larvae of an obligate parasitic
      fly, Wohlfahrtia magnifica (Diptera: Sarcophagidae). These isolates were
      characterized by a polyphasic approach and represent a new lineage of gamma
      Proteobacteria as their closest relative is Xylella fastidiosa (87.1% 16S rDNA
      similarity). The four strains are identical at the 16S rDNA level, the level of
      similarity between them, based on DNA-DNA hybridization, is high (97.8-102.5%)
      and they are similar in their physiological and biochemical characteristics,
      although they differ in their utilization of different sole carbon sources. All
      produce chitinase. They are obligately aerobic: no growth is detected under
      anaerobic conditions, even in the presence of NO3- as terminal electron acceptor.
      Their predominant respiratory quinone is Q-8. The G+C content of their DNA is 42
      mol%. Their cell membrane contains phosphatidylglycerol, diphosphatidylglycerol,
      phosphatidylethanolamine, phosphatidylserine and two unknown polar lipids. Their
      main fatty acids are C18:1, C16:0 and C14:0. To accommodate these bacteria, a new
      genus, Schineria gen. nov., with the type species Schineria larvae sp. nov., is
      proposed.

PMID- 11321086
TI  - Mycoplasma microti sp. nov., isolated from the respiratory tract of prairie voles
      (Microtus ochrogaster).
AB  - Mycoplasmas were isolated from the respiratory tracts of prairie voles (Microtus
      ochrogaster). This paper presents biochemical, serological and molecular genetic
      characterizations of those organisms and proposes a new species, Mycoplasma
      microti sp. nov. The type strain of Mycoplasma microti is strain IL371T (ATCC
      700935T).

PMID- 11321087
TI  - Mycoplasma agassizii sp. nov., isolated from the upper respiratory tract of the
      desert tortoise (Gopherus agassizii) and the gopher tortoise (Gopherus
      polyphemus).
AB  - Biochemical, serological and molecular genetic studies were performed on seven
      mycoplasma isolates that were recovered from the upper respiratory tract of
      clinically ill desert tortoises. The isolates were serologically related to each
      other but serologically distinct from previously described species. Unique
      mycoplasma species-specific 16S rRNA nucleotide sequences were found in the
      proposed type strain. The name Mycoplasma agassizii is proposed for these
      isolates. The type strain is PS6T (= ATCC 700616T) which caused upper respiratory
      tract disease (URTD) in experimentally infected tortoises.

PMID- 11321088
TI  - Mycoplasma alligatoris sp. nov., from American alligators.
AB  - Mycoplasmas were isolated from multiple tissues of diseased American alligators
      (Alligator mississippiensis). This paper presents biochemical, serological and
      molecular genetic characterizations of a lethal pathogen of alligators for which
      the name Mycoplasma alligatoris sp. nov. is proposed. The type strain is A21JP2T
      (ATCC 700619T).

PMID- 11321089
TI  - Taxonomic study of aerobic thermophilic bacilli: descriptions of Geobacillus
      subterraneus gen. nov., sp. nov. and Geobacillus uzenensis sp. nov. from
      petroleum reservoirs and transfer of Bacillus stearothermophilus, Bacillus
      thermocatenulatus, Bacillus thermoleovorans, Bacillus kaustophilus, Bacillus
      thermodenitrificans to Geobacillus as the new combinations G. stearothermophilus,
      G. th.
AB  - Five hydrocarbon-oxidizing strains were isolated from formation waters of
      oilfields in Russia, Kazakhstan and China. These strains were moderately
      thermophilic, neutrophilic, motile, spore-forming rods, aerobic or facultatively
      anaerobic. The G+C content of their DNA ranged from 49.7 to 52.3 mol%. The major
      isoprenoid quinone was menaquinone-7; cellular fatty acid profiles consisted of
      significant amounts of iso-15:0, iso-16:0 and iso-17:0 fatty acids (61.7-86.8% of
      the total). Based on data from 16S rDNA analysis and DNA-DNA hybridization, the
      subsurface isolates could be divided into two groups, one of which consisted of
      strains UT and X and the other of which consisted of strains K, Sam and 34T. The
      new strains exhibited a close phylogenetic relationship to thermophilic bacilli
      of 'Group 5' of Ash et al. [Ash, C., Farrow, J. A. E., Wallbanks, S. & Collins,
      M. D. (1991). Lett Appl Microbiol 13, 202-206] and a set of corresponding
      signature positions of 16S rRNA. Comparative analysis of the 16S rDNA sequences
      and fatty acid compositions of the novel isolates and established species of
      thermophilic bacilli indicated that the subsurface strains represent two new
      species within a new genus, for which the names Geobacillus subterraneus gen.
      nov., sp. nov., and Geobacillus uzenensis sp. nov. are proposed. It is also
      proposed that Bacillus stearothermophilus, Bacillus thermoleovorans, Bacillus
      thermocatenulatus, Bacillus kaustophilus, Bacillus thermoglucosidasius and
      Bacillus thermodenitrificans be transferred to this new genus, with Geobacillus
      stearothermophilus (formerly Bacillus stearothermophilus) as the type species.

PMID- 11321090
TI  - Ureibacillus gen. nov., a new genus to accommodate Bacillus thermosphaericus
      (Andersson et al. 1995), emendation of Ureibacillus thermosphaericus and
      description of Ureibacillus terrenus sp. nov.
AB  - A polyphasic taxonomic study was performed on the type strain of Bacillus
      thermosphaericus DSM 10633T and three related soil isolates. On the basis of
      phenotypic characteristics, chemotaxonomic profiles and phylogenetic data a new
      genus, Ureibacillus gen. nov., is proposed for the strains in the Bacillus
      thermosphaericus cluster. Strains of this cluster fall into two DNA-DNA
      similarity groups: while one group contains the type strain of Ureibacillus
      thermosphaericus comb. nov. and a single soil isolate, the other contains two
      soil isolates. The two groups differed in the composition of isoprenoid quinones
      and some phenotypic properties. These data support the description of a novel
      species of Ureibacillus for which the name Ureibacillus terrenus is proposed. The
      type strain of this new species is TH9AT (= DSM 12654T = LMG 19470T).

PMID- 11321091
TI  - Anaerobranca gottschalkii sp. nov., a novel thermoalkaliphilic bacterium that
      grows anaerobically at high pH and temperature.
AB  - A novel thermoalkaliphilic, obligately anaerobic bacterium was isolated from a
      humid soil sample of a hot inlet of Lake Bogoria, Kenya. The newly isolated
      strain grows optimally at pH 9.5 and 50-55 degrees C and its growth range is pH
      6.0-10.5 and 30-65 degrees C. Unlike the already known thermoalkaliphiles, the
      strain grows heterotrophically on a variety of mono- and polysaccharides
      (glucose, ribose, mannose, fructose, sucrose, maltose, starch, pullulan, xylan
      and cellulose) and on proteinaceous substrates such as yeast extract, peptone and
      tryptone. No dissimilatory sulfate reduction was observed, whereas thiosulfate
      was found to enhance growth when glucose or starch were used as substrates. Under
      optimal conditions, the doubling time is 48 min. Sodium ions are necessary for
      growth, with an optimal concentration of 230 mM (1% NaCl, w/v) at pH 9.5. The rod
      shaped cells are motile in the exponential growth phase under optimal growth
      conditions. Despite the Gram-negative staining and negative KOH assay, the strain
      is a Gram-positive organism, having an atypically thin cell wall. A sheath-like
      structure occurs at the cell separation area and parts of a surface layer-like
      structure were also observed. Based on physiological properties and molecular
      biological analysis, the strain falls within the radiation of the clostridia and
      represents a new species of Anaerobranca within the Clostridium/Bacillus
      subphylum of the Gram-positive bacteria. Strain LBS3T (= DSM 13577T) is named
      Anaerobranca gottschalkii sp. nov. and is designated as the type strain.

PMID- 11321092
TI  - Actinopolymorpha singaporensis gen. nov., sp. nov., a novel actinomycete from the
      tropical rainforest of Singapore.
AB  - A novel actinomycete was isolated from soil in the tropical rainforest of
      Singapore. The cells of this actinomycete are highly pleomorphic. In the early
      stages of growth, most cells are of irregular squarish shape and varied sizes.
      Cells remain attached after cell division, often forming chains or aggregates of
      a few cells. Cells at the end of a chain tend to elongate. With prolonged
      cultivation, cells show different degrees of elongation and enlargement,
      producing branched hyphae of uneven thickness. At the periphery of the colony,
      long hyphae form, which are divided into alternating segments of elongated cells
      and chains of squarish cells. This actinomycete is considerably salt-tolerant,
      able to grow in the presence of 15% NaCl. Chemotaxonomically, it contains LL
      diaminopimelic acid (DAP) in the cell wall, type PI phospholipids and MK-9(H6) as
      the predominant menaquinone. 16S rDNA sequence analysis assigned this
      actinomycete to the family Nocardioidaceae, but its 16S rDNA shared no more than
      91.2% sequence similarity with other members of the family. Based on phenotypic,
      chemotaxonomic and phylogenetic evidence, it is proposed that this actinomycete
      be classified as a new species in a new genus, Actinopolymorpha singaporensis
      gen. nov., sp. nov.

PMID- 11321093
TI  - Aerococcus sanguicola sp. nov., isolated from a human clinical source.
AB  - Phenotypic and phylogenetic studies were performed on an unknown, Gram-positive,
      catalase-negative coccus isolated from human blood. Comparative 16S rRNA gene
      sequencing demonstrated that the organism represents a new subline within the
      genus Aerococcus. The unknown bacterium was readily distinguished from the three
      currently recognized Aerococcus species, Aerococcus christensenii, Aerococcus
      urinae and Aerococcus viridans, by biochemical tests and electrophoretic analysis
      of whole-cell proteins. On the basis of phylogenetic and phenotypic evidence, it
      is proposed that this unknown bacterium from blood be classified as Aerococcus
      sanguicola sp. nov. The type strain of Aerococcus sanguicola is CCUG 43001T (=
      CIP 106533T).

PMID- 11321094
TI  - Hydrogenophilus hirschii sp. nov., a novel thermophilic hydrogen-oxidizing beta
      proteobacterium isolated from Yellowstone National Park.
AB  - A novel thermophilic hydrogen-oxidizing bacterium, Hydrogenophilus hirschii
      Yel5aT (= DSM 11420T = JCM 10831T) has been isolated from the Angel Terrace
      Spring, Yellowstone National Park. The isolate was rod-shaped (1.0-1.5 x 0.8
      microm) with a polarly inserted flagellum. Cells grew chemolithoautotrophically
      under an atmosphere of H2 and CO2 (80:20) in the presence of low concentrations
      of O2 (optimum 2.5%). Organotrophic growth occurred on complex organic substrates
      such as yeast extract and peptone and on organic acids. Carbohydrates and amino
      acids were not utilized. The strain grew between 50 and 67 degrees C; optimal
      growth occurred at a temperature of 63 degrees C. The pH optimum was 6.5. NaCl
      inhibited growth at concentrations higher than 1.5%. The major respiratory
      lipoquinone was ubiquinone-8. Analysis of fatty acids of Yel5aT revealed a
      straight-chain saturated C16:0 as the major component followed by cyclo C17:0 and
      cyclo C19:0. The G+C content of total DNA was 61 mol%. Phylogenetic analysis
      placed the strain in the beta-proteobacteria. The 16S rDNA sequence of strain
      Yel5aT was related to that of Hydrogenophilus thermoluteolus. To our knowledge,
      Hydrogenophilus hirschii is the most thermophilic micro-organism found within the
      proteobacteria that grows in the temperature range 50-68 degrees C.

PMID- 11321095
TI  - Methanobacterium congolense sp. nov., from a methanogenic fermentation of cassava
      peel.
AB  - Strain CT, a non-motile, mesophilic, hydrogenotrophic, methanogenic bacterium,
      was isolated from an anaerobic digester used for the treatment of raw cassava
      peel waste in Congo. The cells were rods, 0.4-0.5 x 2-10 microm in size, and
      stained Gram-positive. Hydrogen and carbon dioxide were the only substrates that
      supported growth and methane production. Methane production, but not growth,
      occurred with CO2 in the presence of either 2-propanol, 2-butanol or
      cyclopentanol as hydrogen donors. The temperature range for growth was 25-50
      degrees C, the optimum being between 37 and 42 degrees C. The optimum pH for
      growth was 7.2; consistent growth and methane production were not observed below
      pH 5.9 or above pH 8.2. The doubling time under optimal growth conditions was 7.5
      h. The DNA base composition was 39.5 mol% G+C. On the basis of 16S rRNA gene
      sequence analysis and phenotypic characteristics, the isolate is proposed as a
      new species of the genus Methanobacterium, namely Methanobacterium congolense sp.
      nov. The type strain is strain CT (= DSM 7095T = OCM 779T).

PMID- 11321096
TI  - Marinitoga camini gen. nov., sp. nov., a rod-shaped bacterium belonging to the
      order Thermotogales, isolated from a deep-sea hydrothermal vent.
AB  - A thermophilic, anaerobic, chemo-organotrophic sulfur-reducing bacterium,
      designated MV1075T, was isolated from a deep-sea hydrothermal chimney sample
      collected on the Mid-Atlantic Ridge. Cells were rod-shaped with a sheath-like
      outer structure, motile with polar flagella and stained Gram-negative. They
      appeared singly, in pairs or in short chains. The temperature range for growth
      was 25-65 degrees C, with an optimum at 55 degrees C. Growth was observed from pH
      5 to pH 9, and the optimum pH was around 7. The salinity range for growth was 15
      70 g sea salt l(-1) (corresponding to 10-45 g NaCl l(-1)), with an optimum at 30
      g l(-1) (20 g NaCl l(-1)). The isolate was able to grow on a broad spectrum of
      carbohydrates or complex proteinaceous substrates. Sulfur was not necessary for
      growth. Growth was inhibited by H2, but, in presence of sulfur, this inhibition
      was removed and H2S was produced. The G+C content of the genomic DNA was 29 mol
      %. Phylogenetic analyses of the 16S rRNA gene located the strain within the order
      Thermotogales, in the domain Bacteria. On the basis of 16S rDNA sequence
      comparisons, in combination with morphological and physiological characteristics,
      it is proposed that the isolate should be described as a novel species of a new
      genus, Marinitoga gen. nov., of which Marinitoga camini sp. nov. is the type
      species. The type strain is MV1075T (= CNCM 1-2413T = DSM 13578T).

PMID- 11321097
TI  - rRNA sequences reflect the ecophysiology and define the toxic cyanobacteria of
      the genus Nodularia.
AB  - Nodularia, a member of the order Nostocales, is a bloom-forming filamentous
      cyanobacterium that possesses the ability to form toxic blooms. The toxin
      produced by Nodularia, nodularin, is a hepatotoxin, similar in structure to the
      heptapeptide toxin microcystin. Twenty-one strains of Nodularia, representing the
      species Nodularia spumigena, Nodularia harveyana and Nodularia sphaerocarpa, were
      analysed for toxin production by protein phosphatase inhibition assay and
      sequenced over the 16S rDNA region. Phylogenetic analysis of Nodularia 16S rDNA
      sequences found that Nodularia clustered into two main groups. An N. spumigena
      cluster was distinct from the benthic species N. harveyana and N. sphaerocarpa.
      There was no distinction between strains isolated from globally diverse
      locations. Nodularin-producing species were restricted to the single,
      evolutionally distinct cluster of N. spumigena. This observation has enabled the
      design of a specific 16S rRNA PCR for the rapid detection of nodularin-producing
      strains. Alignment of 16S rDNA sequences from toxic and non-toxic Nodularia with
      other members of the cyanobacteria allowed the design of both Nodularia generic
      and toxic N. spumigena-specific primers.

PMID- 11321098
TI  - Molecular characterization of planktic cyanobacteria of Anabaena, Aphanizomenon,
      Microcystis and Planktothrix genera.
AB  - Toxic and non-toxic cyanobacterial strains from Anabaena, Aphanizomenon,
      Calothrix, Cylindrospermum, Nostoc, Microcystis, Planktothrix (Oscillatoria
      agardhii), Oscillatoria and Synechococcus genera were examined by RFLP of PCR
      amplified 16S rRNA genes and 16S rRNA gene sequencing. With both methods, high
      16S rRNA gene similarity was found among planktic, anatoxin-a-producing Anabaena
      and non-toxic Aphanizomenon, microcystin-producing and non-toxic Microcystis, and
      microcystin-producing and non-toxic Planktothrix strains of different
      geographical origins. The respective sequence similarities were 99.9-100%, 94.2
      99.9% and 99.3-100%. Thus the morphological characteristics (e.g. Anabaena and
      Aphanizomenon), the physiological (toxicity) characteristics or the geographical
      origins did not reflect the level of 16S rRNA gene relatedness of the closely
      related strains studied. In addition, cyanobacterial strains were fingerprinted
      with repetitive extragenic palindromic (REP)- and enterobacterial repetitive
      intergenic consensus (ERIC)-PCR. All the strains except two identical pairs of
      Microcystis strains had different band profiles. The overall grouping of the
      trees from the 16S rRNA gene and the REP- and ERIC-PCR analyses was similar.
      Based on the 16S rRNA gene sequence analysis, four major clades were formed. (i)
      The clade containing filamentous heterocystous cyanobacteria was divided into
      three discrete groups of Anabaena/Aphanizomenon, Anabaena/Cylindrospermum/
      Nodularia/Nostoc and Calothrix strains. The three other clades contained (ii)
      filamentous non-heterocystous Planktothrix, (iii) unicellular non-heterocystous
      Microcystis and (iv) Synechococcus strains.

PMID- 11321099
TI  - Dechloromonas agitata gen. nov., sp. nov. and Dechlorosoma suillum gen. nov., sp.
      nov., two novel environmentally dominant (per)chlorate-reducing bacteria and
      their phylogenetic position.
AB  - Previous studies on the ubiquity and diversity of microbial (per)chlorate
      reduction resulted in the isolation of 20 new strains of dissimilatory
      (per)chlorate-reducing bacteria. Phylogenetic analysis revealed that all of the
      isolates were members of the Proteobacteria with representatives in the alpha-,
      beta- and gamma-subclasses. The majority of the new isolates were located in the
      beta-subclass and were closely related to each other and to the phototrophic
      Rhodocyclus species. Here an in-depth analysis of these organisms which form two
      distinct monophyletic groups within the Rhodocyclus assemblage is presented. Two
      new genera, Dechloromonas and Dechlorosoma, are proposed for these beta-subclass
      lineages which represent the predominant (per)chlorate-reducing bacteria in the
      environment. The type species and strains for these new genera are Dechloromonas
      agitata strain CKBT and Dechlorosoma suillum strain PST, respectively.

PMID- 11321100
TI  - Paenibacillus borealis sp. nov., a nitrogen-fixing species isolated from spruce
      forest humus in Finland.
AB  - Seven spore-forming, nitrogen-fixing bacterial isolates from spruce forest humus
      in Finland were studied using the polyphasic approach. PCR amplification of 16S
      rRNA gene fragment with specific primers showed that the isolates were members of
      Paenibacillus. Levels of 16S rDNA similarity between the isolates were 97.3
      100.0% and those between the isolates and other Paenibacillus species were 90.3
      96.5%. The highest similarities were observed with Paenibacillus azotofixans and
      Paenibacillus durus. Ribotyping with EcoRI and PvuII restriction showed a high
      diversity in the Paenibacillus species and distinguished the isolates from these
      closely related species. The main whole-cell fatty acids were anteiso-C15:0 (33
      48%), straight-chain C14:0 (7-21%) and C16:0 (9-20%), and iso-C15:0 (6-15%).
      Electron microscopy revealed a unique striped morphology of the spore surfaces.
      Based on phylogenetic inference and phenotypic and chemotaxonomic
      characteristics, these isolates are proposed as a new species, Paenibacillus
      borealis sp. nov., the type strain of which is KK19T (= DSM 13188T = CCUG
      43137T).

PMID- 11321101
TI  - Classification of Ralstonia pickettii biovar 3/'thomasii' strains (Pickett 1994)
      and of new isolates related to nosocomial recurrent meningitis as Ralstonia
      mannitolytica sp. nov.
AB  - Strains isolated independently from two patients could be recognized as Ralstonia
      pickettii biovar 3/'thomasii'. The 16S rDNA sequences of these strains and two
      other strains of R. pickettii biovar 3/'thomasii' clustered at less than 98%
      similarity versus all other described Ralstonia species and at less than 97 %
      versus the two other R. pickettii biovars. The separate species status of R.
      pickettii biovar 3/'thomasii' was confirmed by DNA-DNA hybridization, indicating
      less than 60% DNA homology with the R. pickettii biovars Va-1 and Va-2 and with
      two as-yet unclassified but biochemically similar Ralstonia strains.
      Phenotypically, this Ralstonia species can be distinguished from all described
      Ralstonia species by its acidification of D-arabitol and mannitol and by its lack
      of nitrate reduction and of alkalinization of tartrate and from two as-yet
      unclassified Ralstonia strains only by its lack of nitrate reduction. The name
      Ralstonia mannitolytica sp. nov. is proposed, reflecting the characteristic
      acidification of mannitol. Resistance to desferrioxamine is another difference
      from R. pickettii and Ralstonia solanacearum. Although several nosocomial
      outbreaks have been associated with R. mannitolytica, life-threatening infections
      have not yet been reported, possibly due to misidentification as Pseudomonas
      fluorescens or Burkholderia cepacia. In at least one of the two cases reported
      here, the R. mannitolytica isolate was found to be clinically relevant, causing
      recurrent nosocomial meningitis, with an infected implanted catheter as the
      source. The type strain of R. mannitolytica is NCIMB 10805T (= LMG 6866T), which
      was isolated during the first described outbreak as 'Pseudomonas thomasii' at St
      Thomas' Hospital, London, UK, in 1971.

PMID- 11321102
TI  - Asaia siamensis sp. nov., an acetic acid bacterium in the alpha-proteobacteria.
AB  - Five bacterial strains were isolated from tropical flowers collected in Thailand
      and Indonesia by the enrichment culture approach for acetic acid bacteria.
      Phylogenetic analysis based on 16S rRNA gene sequences showed that the isolates
      were located within the cluster of the genus Asaia. The isolates constituted a
      group separate from Asaia bogorensis on the basis of DNA relatedness values.
      Their DNA G+C contents were 58.6-59.7 mol%, with a range of 1.1 mol%, which were
      slightly lower than that of A. bogorensis (59.3-61.0 mol%), the type species of
      the genus Asaia. The isolates had morphological, physiological and biochemical
      characteristics similar to A. bogorensis strains, but the isolates did not
      produce acid from dulcitol. On the basis of the results obtained, the name Asaia
      siamensis sp. nov. is proposed for these isolates. Strain S60-1T, isolated from a
      flower of crown flower (dok rak, Calotropis gigantea) collected in Bangkok,
      Thailand, was designated the type strain ( = NRIC 0323T = JCM 10715T = IFO
      16457T).

PMID- 11321103
TI  - Thioalkalimicrobium aerophilum gen. nov., sp. nov. and Thioalkalimicrobium
      sibericum sp. nov., and Thioalkalivibrio versutus gen. nov., sp. nov.,
      Thioalkalivibrio nitratis sp.nov., novel and Thioalkalivibrio denitrificancs sp.
      nov., novel obligately alkaliphilic and obligately chemolithoautotrophic sulfur
      oxidizing bacteria from soda lakes.
AB  - Forty-three strains of obligately chemolithoautotrophic sulfur-oxidizing bacteria
      were isolated from highly alkaline soda lakes in south-east Siberia (Russia) and
      in Kenya using a specific enrichment procedure at pH 10. The main difference
      between the novel isolates and known sulfur bacteria was their potential to grow
      and oxidize sulfur compounds at pH 10 and higher. The isolates fell into two
      groups that were substantially different from each other physiologically and
      genetically. Most of the Siberian isolates belonged to the group with a low DNA
      G+C content (48.0-51.2 mol%). They were characterized by a high growth rate, a
      low growth yield, a high cytochrome content, and high rates of oxidation of
      sulfide and thiosulfate. This group included 18 isolates with a DNA homology of
      more than 40%, and it is described here as a new genus, Thioalkalimicrobium, with
      two species Thioalkalimicrobium aerophilum (type species) and Thioalkalimicrobium
      sibericum. The other isolates, mainly from Kenyan soda lakes, fell into a group
      with a high DNA G+C content (61.0-65.6 mol%). In general, this group was
      characterized by a low growth rate, a high molar growth yield and low, but
      relatively equal, rates of oxidation of thiosulfate, sulfide, elemental sulfur
      and polythionates. The group included 25 isolates with a DNA homology of more
      than 30%. It was less compact than Thioalkalimicrobium, containing
      haloalkalophilic, carotenoid-producing, nitrate-reducing and facultatively
      anaerobic denitrifying strains. These bacteria are proposed to be assigned to a
      new genus, Thioalkalivibrio, with three species Thioalkalivibrio versutus (type
      species), Thioalkalivibrio denitrificans and Thioalkalivibrio nitratis.
      Phylogenetic analysis revealed that both groups belong to the gamma
      Proteobacteria. The Thioalkalimicrobium species were closely affiliated with the
      neutrophilic chemolithoautotrophic sulfur bacteria of the genus Thiomicrospira,
      forming a new alkaliphilic lineage in this cluster. In contrast, Thioalkalivibrio
      was not related to any known chemolithoautotrophic taxa, but was distantly
      associated with anaerobic purple sulfur bacteria of the genus Ectothiorhodospira.

PMID- 11321104
TI  - Geobacter hydrogenophilus, Geobacter chapellei and Geobacter grbiciae, three new,
      strictly anaerobic, dissimilatory Fe(III)-reducers.
AB  - Recent studies on the diversity and ubiquity of Fe(III)-reducing organisms in
      different environments led to the isolation and identification of four new
      dissimilatory Fe(III)-reducers (strains H-2T, 172T, TACP-2T and TACP-5). All four
      isolates are non-motile, Gram-negative, freshwater, mesophilic, strict anaerobes
      with morphology identical to that of Geobacter metallireducens strain GS-15T.
      Analysis of the 16S rRNA sequences indicated that the new isolates belong to the
      genus Geobacter, in the delta-Proteobacteria. Significant differences in
      phenotypic characteristics, DNA-DNA homology and G+C content indicated that the
      four isolates represent three new species of the genus. The names Geobacter
      hydrogenophilus sp. nov. (strain H-2T), Geobacter chapellei sp. nov. (strain
      172T) and Geobacter grbiciae sp. nov. (strains TACP-2T and TACP-5) are proposed.
      Geobacter hydrogenophilus and Geobacter chapellei were isolated from a petroleum
      contaminated aquifer and a pristine, deep, subsurface aquifer, respectively.
      Geobacter grbiciae was isolated from aquatic sediments. All of the isolates can
      obtain energy for growth by coupling the oxidation of acetate to the reduction of
      Fe(III). The four isolates also coupled Fe(III) reduction to the oxidation of
      other simple, volatile fatty acids. In addition, Geobacter hydrogenophilus and
      Geobacter grbiciae were able to oxidize aromatic compounds such as benzoate,
      whilst Geobacter grbiciae was also able to use the monoaromatic hydrocarbon
      toluene.

PMID- 11321105
TI  - Characterization of halobenzoate-degrading, denitrifying Azoarcus and Thauera
      isolates and description of Thauera chlorobenzoica sp. nov.
AB  - The taxonomic relationships of Azoarcus and Thauera isolates in the beta-subclass
      of the Proteobacteria capable of degrading fluoro-, chloro- or bromobenzoate
      under denitrifying conditions were analysed. A detailed classification of these
      strains was performed using a polyphasic approach, which included studies on
      morphology, phenotypic characterization, fatty acid analysis, 16S rRNA gene
      sequence analysis, 16S rRNA gene mapping (ribotyping) and DNA-DNA hybridization.
      The analyses of fatty acids and 16S rRNA gene sequencing differentiated strains
      2FB2, 2FB6 and 4FB10 as new members of the genus Azoarcus and strains 4FB1, 4FB2,
      3CB2, 3CB3 and 3BB1 as new members of the genus Thauera. DNA-DNA hybridization
      experiments established that strains 2FB2, 2FB6 and 4FB10 belong to the species
      Azoarcus tolulyticus. Strains 3CB2 and 3CB3 were assigned to the species Thauera
      aromatica on the basis of DNA-DNA hybridization and ribotyping experiments.
      Strains 4FB1, 4FB2 and 3BB1 showed close relatedness with strain 3CB-1T,
      previously described as T. aromatica genomovar chlorobenzoica. This group of
      strains is clearly differentiated from the species T. aromatica on the basis of
      16S rRNA sequence analysis, DNA homology and ribotyping analysis. Strains 3CB-1T,
      4FB1, 4FB2 and 3BB1 are proposed as members of the new species Thauera
      chlorobenzoica sp. nov., strain 3CB-1T (= ATCC 700723T) being the type strain.

PMID- 11321106
TI  - Sphingomonas cloacae sp. nov., a nonylphenol-degrading bacterium isolated from
      wastewater of a sewage-treatment plant in Tokyo.
AB  - A nonylphenol-assimilating bacterium isolated at a sewage-treatment plant in
      Tokyo was studied phenotypically, genotypically and phylogenetically. Analysis of
      the 16S rDNA sequence, the G+C content of the DNA (63 mol%) and the isoprenoid
      quinone composition, as well as the presence of sphingoglycolipid and the whole
      cell fatty acid profile, revealed that the isolate is a member of the genus
      Sphingomonas. However, the sequence similarity of the 16S rDNA with that of known
      Sphingomonas spp. was found to be at most 96%, implying that the isolate is
      distinctive. Furthermore, the results of DNA-DNA hybridization experiments and
      its physiological characteristics clearly indicated that the isolate represents a
      new Sphingomonas species, for which the name Sphingomonas cloacae is proposed;
      strain S-3T (= JCM 10874T = IAM 14885) is the type strain.

PMID- 11321107
TI  - Methylosarcina fibrata gen. nov., sp. nov. and Methylosarcina quisquiliarum
      sp.nov., novel type 1 methanotrophs.
AB  - Two novel species of obligate methane-oxidizing bacteria, isolated from landfill
      soil, were characterized. Both strains were unusual in that some members of the
      population grew in irregularly shaped, refractile cell packets that resembled
      sarcina-like clusters. Electron microscopy revealed that the cell packets were
      covered with a slime layer and the cells contained many large granular inclusion
      bodies. The individual cells of each strain were sometimes motile and had
      differing morphologies. Isolate AML-C10T was always coccoidal in shape, and the
      cells were covered with extracellular fibrils. Isolate AML-D4T was pleomorphic,
      changing from rod to coccal form, sometimes exhibiting an unusual fusiform
      morphology. AML-D4T lacked the extensive fibrillar matrix observed with AML-C10T.
      Both strains utilized only methane and methanol as carbon sources. In stationary
      phase, the cells of each strain swelled in size and formed cysts. Aside from
      morphological differences, strains could also be distinguished from each other by
      cellular protein patterns, as well as by temperature and pH tolerances. 16S rDNA
      phylogenetic analysis showed that these are type I methanotrophs (family:
      Methylococcaceae) most closely related to the Methylobacter/Methylomicrobium
      clade, although they form a monophyletic grouping supported by moderately high
      bootstrap values. By 16S rDNA database searches, the most similar species to both
      isolates were Methylobacter spp. However, partial particulate methane
      monooxygenase sequence analysis suggested that these bacteria might be more
      closely related to Methylomicrobium than Methylobacter. Furthermore, cellular
      fatty acid profiles of the strains more closely resemble those of
      Methylomicrobium, although the absence of significant levels of 16:1omega5c
      argues for the uniqueness of these two strains. On the basis of the results
      described here, it is proposed that a new genus should be created, Methylosarcina
      gen. nov., harbouring two species, Methylosarcina fibrata sp. nov. (type species)
      and Methylosarcina quisquiliarum sp. nov. The type strains are AML-C10T (= ATCC
      700909T = DSM 13736T) and AML-D4T (= ATCC 700908T = DSM 13737T), respectively.

PMID- 11321108
TI  - Comparison of sequence analysis of 16S-23S rDNA spacer regions, AFLP analysis and
      DNA-DNA hybridizations in Bradyrhizobium.
AB  - The sequences of the 16S-23S rDNA intergenic spacer region of 62 strains of
      Bradyrhizobium, including representatives of the three valid species, were
      determined. The majority of strains had a single rRNA operon type and all
      contained a tRNA(Ala) and a tRNA(Ile) gene. Analysis of the sequence data
      produced groupings in line with previously obtained AFLP data. DNA-DNA
      hybridizations were performed to determine to what extent spacer sequences and
      AFLP profiles reflected the overall genomic similarities. Strains belonging to
      the same AFLP group, and strains with spacer sequences diverging less than 4%,
      were found to belong to the same genospecies. More remote relationships (DNA
      homology levels of 40-60%) between species were reflected in the spacer sequence
      analysis, but not in the AFLP analysis. For the genus Bradyrhizobium, 16S-23S
      rDNA spacer sequence analysis provides taxonomic information similar, but not
      always identical to that obtained by DNA-DNA hybridizations. Our results indicate
      that this genus consists of a group of four highly related genospecies
      (Bradyrhizobium japonicum, Bradyrhizobium liaoningense and two other genospecies)
      and at least three other genospecies, one of which is Bradyrhizobium elkanii.

PMID- 11321109
TI  - Re-evaluation of the classical Mycoplasma lipophilum cluster (Weisburg et al.
      1989) and description of two new clusters in the hominis group based on 16S rDNA
      sequences.
AB  - The Mycoplasma lipophilum cluster (Weisburg et al. 1989) in the hominis group of
      the mollicutes is re-evaluated in this work to update the phylogenetic framework
      for classification of species within the genus Mycoplasma. Therefore, sequences
      of the 16S rRNA gene were determined from previously described species, and 11
      were found to be closely related to the M. lipophilum cluster. A selection of
      members of the other hitherto defined clusters of the hominis group was included
      for phylogenetic analysis, revealing that the classical M. lipophilum cluster
      could be re-organized into two clusters, namely the M. lipophilum cluster and the
      Mycoplasma bovis cluster. The former was found to contain two species, while the
      latter contained 20 species. The two clusters were closely related, sharing an
      ancestral branch with the Mycoplasma synoviae cluster. Furthermore, the M. bovis
      cluster could be divided into subclusters. Interestingly, two species, Mycoplasma
      equigenitalium and Mycoplasma elephantis, formed a distinct and early branch of
      the M. lipophilum, M. bovis and M. synoviae clusters. This entity was termed the
      M. equigenitalium cluster. The clusters and subclusters could be verified by
      using neighbour-joining and maximum-likelihood analyses on a variety of data
      sets, bootstrap calculations, secondary structure analysis and signature
      nucleotides. Therefore, the new 16S rDNA data presented in this work were used to
      re-evaluate the M. lipophilum cluster, leading to the definition of two
      additional clusters. At present, the mollicutes belonging to the hominis group
      can be classified into ten evolutionary lineages.

PMID- 11321110
TI  - Amycolatopsis albidoflavus sp. nov.
AB  - The generic position of an actinomycete strain, 'Pseudonocardia sp.' IMSNU 22139,
      was investigated by the phylogenetic analysis of 16S rDNA sequence. Comparative
      studies of 16S rDNA sequences indicated that this organism consistently formed a
      distinct clade within the radiation of the genus Amycolatopsis of the family
      Pseudonocardiaceae. This organism was also found to have chemotaxonomic
      properties consistent with those of the genus Amycolatopsis, which were
      represented by a type IV cell wall (meso-diaminopimelic acid, arabinose and
      galactose), a major menaquinone of MK-9(H4), a predominant fatty acid of 14
      methylpentadecanoic acid, phosphatidylmethylethanolamine as a diagnostic
      phospholipid (a phospholipid type PII pattern) and DNA base composition of 68.5
      mol% G+C. On the basis of physiological properties, cellular fatty acid profiles
      and its unique phylogenetic position, this organism is readily differentiated
      from all of the validly described species of the genus Amycolatopsis, and the
      name Amycolatopsis albidoflavus sp. nov. is proposed for it. The type strain is
      IMSNU 22139T (= KCTC 9471T = ATCC 53205T).

PMID- 11321111
TI  - Campylobacter hominis sp. nov., from the human gastrointestinal tract.
AB  - Sequences of 16S rDNA of a novel campylobacter from faeces of healthy humans were
      previously shown to originate from a new taxon, 'Candidatus Campylobacter
      hominis', which could not be cultured. Since phylogenetic analysis suggested that
      anaerobic conditions might be required for growth, an isolation strategy was
      developed employing initial non-selective membrane filtration onto fastidious
      anaerobe agar. Campylobacters were then isolated from the resulting mixed
      microbial flora by a dilution strategy and/or by immunomagnetic separation with
      genus-specific polyclonal antibody. Isolates were identified by a genus and taxon
      specific PCR assay, and 16S rDNA nucleotide sequence analysis was carried out.
      All isolates exhibited the typical Campylobacter characteristics of being non
      fermentative, oxidase-positive, catalase-negative and Gram-negative. Unusually,
      however, they were straight rods lacking flagella. The 16S rDNA nucleotide
      sequence analysis, DNA and mol% G+C were consistent with a new Campylobacter
      species whose nearest phylogenetic neighbours were Campylobacter gracilis and
      Campylobacter sputorum. The unique species status of the isolates was further
      confirmed by taxonomic analysis of 47 phenotypic characteristics. The name
      Campylobacter hominis sp. nov. is proposed for the new species, the type strain
      of which is NCTC 13146T (= LMG 19568T).

PMID- 11321112
TI  - Hahella chejuensis gen. nov., sp. nov., an extracellular-polysaccharide-producing
      marine bacterium.
AB  - A bacterial strain, designated 96CJ10356T, which produced abundant extracellular
      polysaccharides and red pigment was isolated from marine sediment collected from
      Marado, Cheju Island, Republic of Korea. The organism is Gram-negative, aerobic,
      rod-shaped and motile. Growth was not observed in the absence of NaCl, and was
      optimal at an NaCl concentration of 2%. The strain contained oxidase and
      catalase, and was able to hydrolyse aesculin and gelatin. The major cellular
      fatty acids were saturated or monounsaturated straight-chain fatty acids. An
      almost complete 16S rDNA sequence of the test strain was determined. Phylogenetic
      analysis based on the neighbour-joining and Fitch-Margoliash methods indicated
      that the organism formed a distinct phyletic line within the gamma
      Proteobacteria. This relationship was also supported by sequence comparison, as
      no valid bacterial species showed more than 90% sequence homology with the
      isolate. It is clear from polyphasic evidence that the isolate merits the status
      of genus in the gamma subclass of the Proteobacteria, and the name Hahella
      chejuensis gen. nov., sp. nov. is proposed for the marine isolate 96CJ10356T (=
      KCTC 2396T = IMSNU 11157T).

PMID- 11321113
TI  - Relationship of 16S rRNA sequence similarity to DNA hybridization in prokaryotes.
AB  - The relationship between 16S rRNA sequence similarity (S) and the extent of DNA
      hybridization (D) was well described by the equation In(-InD) = 0.53 [In(
      InS)]+2.201 when D was determined by either the S1 nuclease or membrane filter
      methods. When the presence of nonultrametric rRNA sequences and differences
      between genera or families were controlled, this relationship accounted for 78%
      of the variability of D given S, and it was possible to estimate the distribution
      of D from S with a known precision. Thus, D<0.70 was expected to occur 50, 95 and
      99% of the time when S was 0.998, 0.992 and 0.986, respectively. The relationship
      between D and S varied between prokaryotic taxa even within the same subphylum,
      and more precise estimates of D could be made when the relationship for a
      particular taxon was known. The relationship between D and S was not
      significantly different between the prokaryotic domains, and S appeared to be a
      quasi-molecular clock of approximately constant rate when averaging effects and
      stochastic factors were taken into account. The relationship between logD and
      logS was nonlinear, and D provided a very poor measure of relatedness for
      distantly related organisms. For instance, within the range 1.0 >S>> 0.95, D
      decreased from 1.0 to 0.15; and within the range 0.95 >S> 0.90, D decreased from
      0.15 to 0.06. Lastly, at least some of the rRNA sequences from about one-third of
      the taxa examined had nonultrametric properties where S was much lower than
      expected from the value of D. For these taxa, S was a poor indicator of
      relatedness for closely related strains. Thus, the ultrametric properties of rRNA
      sequences should be tested before making taxonomic or phylogenetic conclusions
      based upon S.

PMID- 11321114
TI  - Actinomyces catuli sp. nov., from dogs.
AB  - An Actinomyces-like bacterium was recovered from two dogs. Based on cellular
      morphology and biochemical criteria, the unknown bacterium resembled the genus
      Actinomyces but it did not appear to correspond to any of the currently
      recognized species of this genus. PAGE analysis of whole-cell proteins confirmed
      that the strain was phenotypically distinct from all other Actinomyces species
      and comparative 16S rRNA gene sequencing showed that the bacterium represents an
      unknown sub-line within the genus. Based on phenotypic and phylogenetic evidence,
      it is proposed that the bacterium from dogs be classified as a new species of the
      genus Actinomyces, Actinomyces catuli. The type strain of Actinomyces catuli is
      CCUG 41709T (= CIP 106507T).

PMID- 11321115
TI  - Aerococcus urinaehominis sp. nov., isolated from human urine.
AB  - Phenotypic and phylogenetic studies were performed on an unknown Gram-positive
      catalase-negative coccus isolated from human urine. Comparative 16S rRNA gene
      sequencing demonstrated that the organism represents a new subline within the
      genus Aerococcus. The unknown bacterium was readily distinguished from the three
      currently recognized Aerococcus species, Aerococcus christensenii, Aerococcus
      urinae and Aerococcus viridans, by biochemical tests and electrophoretic analysis
      of whole-cell proteins. Based on phylogenetic and phenotypic evidence, it is
      proposed that the unknown bacterium from urine be classified as Aerococcus
      urinaehominis sp. nov. The type strain of Aerococcus urinaehominis is CCUG
      42038bT (= CIP 106675T).

PMID- 11321116
TI  - Polyphasic taxonomy of the basidiomycetous yeast genus Rhodosporidium:
      Rhodosporidium kratochvilovae and related anamorphic species.
AB  - The phenotypic and genetic heterogeneity of the basidiomycetous yeast species
      Rhodosporidium kratochvilovae was investigated in a group of recent isolates and
      collection strains. A polyphasic taxonomic approach was followed which included
      micromorphological studies, nuclear staining, determination of sexual
      compatibility, physiological characterization, comparison of electrophoretic
      isoenzyme patterns, PCR fingerprinting, determination of mol% G+C, DNA-DNA
      reassociation experiments and 26S and ITS rDNA sequence analysis. The results
      allowed a more natural circumscription of the species, both from the genetic and
      phenotypic perspectives. The relationships with anamorphic species of the genus
      Rhodotorula were studied and isolates previously identified as Rhodotorula
      glutinis were found to belong to Rhodosporidium kratochvilovae. Other isolates
      included in the study were found to represent members of Rhodotorula glutinis
      var. dairenensis. Rhodosporidium kratochvilovae was found to include
      heterothallic strains, besides those already known to be self-sporulating. A
      total of 17 isolates, which were found to belong to this species, were
      heterothallic, self-sporulating and anamorphic strains. It is anticipated that
      integrated polyphasic studies of basidiomycetous yeasts will provide a more
      coherent classification system and the basis for accurate identification schemes,
      which in turn are essential for detailed ecological studies.

PMID- 11321117
TI  - Candida orba sp. nov., a new cactus-specific yeast species from Queensland,
      Australia.
AB  - A new species of yeast from decaying cladodes of Opuntia cactus, Candida orba, is
      described. This species is a member of a four-species clade of cactophilic
      yeasts. The new species has only been found in one region of Queensland,
      Australia, where it was presumably introduced during attempts to eradicate
      prickly pear cactus. DNA-DNA relatedness, phylogenetic analysis, physiological
      differences, killer-sensitivity profiles and mating reactions establish the
      distinctness of the taxon as a new species. C. orba is most closely related to
      Phaffomyces thermotolerans, a species found associated with columnar cacti in the
      North American Sonoran Desert. The type strain of C. orba, isolated from rotting
      cladodes of Opuntia stricta in the State of Queensland, Australia, is strain UCD
      FST 84-833.1T (= CBS 8782T = NRRL Y-27336T = ATCC MYA-341). Only the h- mating
      type of the species has been recovered. The lack of the opposite mating type
      could be the result of a bottleneck during its introduction to Australia. The
      original geographic/host distribution of this species in the Americas is unknown.

PMID- 11321118
TI  - Taxonomic ambiguities: a case history.

PMID- 11321119
TI  - Rhodocista centenaria vs Rhodospirillum centenum: a reply to Gest and Favinger.

PMID- 11321120
TI  - Recommendations of the subcommittee on the taxonomy of Campylobacter and related
      bacteria.
AB  - The ICSB Subcommittee on the taxonomy of Campylobacter and related bacteria has
      discussed several contemporaneous issues and makes the following recommendations.
      (i) The reported synonymy between Campylobacter coli and Campylobacter hyoilei
      was based on valid taxonomic arguments. The subcommittee therefore discourages
      the use of the name C. hyoilei. (ii) The revised infrasubspecific nomenclature of
      Campylobacter sputorum is endorsed. C sputorum is subdivided into C. sputorum
      biovar sputorum (characterized by the absence of catalase and urease activity);
      C. sputorum biovar faecalis (characterized by catalase but not urease activity);
      and C. sputorum biovar paraureolyticus (characterized by urease, but not catalase
      activity). (iii) The subcommittee points out that 'Flexispira rappini' is a taxon
      that is circumscribed by means of morphological criteria. It encompasses multiple
      Helicobacter species, including Helicobacter billis and Helicobacter trogontum.
      (iv) Finally, the subcommittee wishes to point out that the etymology of several
      specific or subspecific epithets of Campylobacter taxa has been corrected and
      that the spelling of the epithet 'fecalis' was corrected to 'faecalis'.

PMID- 11321121
TI  - Recommended conservation of the names Streptococcus sanguis, Streptococcus
      rattus, Streptococcus cricetus, and seven other names included in the Approved
      Lists of Bacterial Names. Request for an opinion.
AB  - With reference to the first Principle of the International Code of Nomenclature
      of Bacteria, which emphasizes stability of names, it is proposed that the
      original names Streptococcus sanguis, Streptococcus rattus, Streptococcus
      cricetus, Erwinia ananas, Eubacterium tarantellus, Lactobacillus sake,
      Nitrosococcus oceanus, Pseudomonas betle, Rickettsia canada and Streptomyces
      rangoon, all included in the Approved Lists of Bacterial Names, be conserved.
      Request for an Opinion.

PMID- 11321122
TI  - Nomenclatural type of orders: corrections necessary according to Rules 15 and 21a
      of the Bacteriological Code (1990 Revision), and designation of appropriate
      nomenclatural types of classes and subclasses. Request for an opinion.
AB  - An important aspect of the Bacteriological Code (1990 Revision) is the
      designation of nomenclatural types to the various taxonomic ranks to provide a
      suitable reference point for the unambiguous identification of the taxon.
      Although the nomenclatural type of the species is the designated strain, and the
      nomenclatural type of the genus is the type species, the nomenclatural type of
      both the family and the order is the 'genus on whose name the name of the
      relevant taxon is based'. However, in some cases a genus has not been designated
      as the nomenclatural type of an order. Twelve cases that are contrary to the
      Rules listed and appropriate corrections are proposed. In addition, several
      classes have been named for which no nomenclatural type has been designated; this
      brings into question whether they can be considered to have been validly
      published, as well as highlighting the fact that they would be/are illegitimate.

PMID- 11321123
TI  - A personal glimpse of clinical infectious diseases: 1949-1999.
AB  - We have witnessed the advent of the antibiotic era and the development of potent
      immunization agents in the second half of the 20th century. These remarkable
      scientific tools enable us to treat and control infectious diseases effectively.
      Yet the development of microbial resistance to antimicrobial agents and the
      emergence of new or previously unrecognized infectious diseases continue to
      challenge the medical and public health professionals. Most ominously, the ill
      natured terrorists and mistrustful administrators in certain nations have
      capitalized on the modern microbial technology to create means for bioterrorism
      and biological warfare. When will humans ever learn?

PMID- 11321124
TI  - Screening procedure from cattle feces and the prevalence of Escherichia coli
      O157:H7 in Taiwan dairy cattle.
AB  - A procedure has been established for screening Escherichia coli O157:H7 from
      bovine feces. It consists of four steps: enrichment, selective culture,
      phenotyping and genotyping. Modified trypticase soy broth (mTSB) containing 20
      microg/mL of novobiocin was used for the enrichment step. The selective culture
      step was done using sorbitol MacConkey agar containing 0.05 microg/mL of cefixime
      and 2.5 microg/mL of potassium tellurite. The phenotyping steps include: species
      confirmation as E. coli, serotyping to O157 and H7, and the detection of
      verocytotoxin (VT) production. Genotyping was made up of confirmation of the
      presence of the O157 antigen (rfb), the H7 antigen (ficC), the adherence factor
      (eaeA), hemolysin (hlyA), and VT production (vt I and vt II) by polymerase chain
      reaction. mTSB gave better enrichment for E. coli O157 than gram-negative (GN)
      broth. The detection limit for this screening procedure was 0.85 +/- 0.5 cfu/g.
      Using the screening procedure described above, E. coli O157 was found in four out
      of 3062 (0.13%) fresh bovine fecal specimens, and in two out of 78 (2.56%) dairy
      herds in Taiwan. Three out of the four detected strains were vt II producing E.
      coli O157:H7, while the other was E. coli O157:H7 which lacked VT-producing
      ability.

PMID- 11321125
TI  - Effects of BCG on ovalbumin-induced bronchial hyperreactivity in a guinea pig
      asthma model.
AB  - To test the effects of Bacillus Calmette-Guerin (BCG) on ovalbumin (OVA)-induced
      airway hyper-reactivity in guinea pigs, a total of 40 young guinea pigs was
      individually vaccinated subcutaneously with 0.2 mL of 2% OVA, 50 microg BCG, or a
      mixture of OVA and BCG (OVA+BCG). Airways were sensitized using nebulization with
      1% OVA for 3 min once a week for two applications, followed by 2% OVA nebulized
      challenge for 3 min 1 week after the last application. Different concentrations
      of methacholine were used to detect airway hyperreactivities. At the third week,
      the guinea pigs were nebulized with either methacholine or OVA to test airway
      hyperreactivity. The OVA-vaccinated group presented with severe airway
      hyperresponsiveness after OVA and methacholine challenges; the BCG-vaccinated
      group showed mild airway hyperreactivity; and the OVA+BCG group showed the least
      amount of airway hyperreactivity. Lung histopathology in all groups, except the
      OVA+BCG-vaccinated group, showed severe thickening of the alveolar walls which
      became firmly fibrotic, and narrowing of the alveolar spaces was also noted. The
      guinea pigs in the OVA+BCG-vaccinated group had similar pulmonary morphology with
      that of naive guinea pigs, and had mild cell infiltration in the alveolar wall.
      The results of the skin biopsies at 6 h (2% OVA, 0.05 mL) and 36 h (20 microg
      PPD, 0.05 mL) after purified protein derivative (PPD) inoculation showed that
      infiltration of eosinophils and activation of CD4+ T-cells occurred in the OVA
      vaccinated group. In the BCG-vaccinated groups, infiltration of CD4+ T-cells,
      CD8+ T-cells and macrophages occurred. OVA-specific IgG2 increased in the BCG
      vaccinated groups after OVA-induced airway hyperreactivity occurred. The
      peripheral cell subpopulation showed that there was obviously increased
      activation of CD4+ and CD8+ T-cells in the OVA+BCG-vaccinated group. The
      phagocytic activity of macrophages also increased in both BCG- and OVA+BCG
      vaccinated groups. The prevention of OVA-induced airway hyperreactivities using
      BCG vaccination in conjugation with OVA in these young guinea pigs indicated that
      it might be a good approach to avoid allergic reactions in humans.

PMID- 11321126
TI  - Soluble CD4 suppresses T-dependent IgG2a antibody response of CD4 loosing mice by
      inhibiting IFNgamma production.
AB  - To analyze the role of soluble CD4 (sCD4) in antibody (Ab) responses in CD4
      loosing (CD4L) mice, experiments have been done in comparing CD4L mice with CD4
      knockout (CD4KO) mice on the same C57BL/6 background. The CD4L mice have a defect
      in CD4 expression where CD4 mRNA is alternatively spliced so that a transmembrane
      portion is deleted and sCD4 are secreted without expression of membrane-bound
      CD4. Significantly reduced immunoglobulin (Ig) G2a isotype Ab response against a
      T-dependent antigen (Ag), trinitrophenyl-keyhole limpet hemocyanin (TNP-KLH), was
      found in CD4L mice as compared with those of CD4KO mice. Gamma interferon
      (IFNgamma) production of KLH-stimulated lymph nodes cells was significantly
      reduced in CD4L mice as compared with those in CD4KO mice. The positive
      proportion of cells expressing CD40 ligand from CD4KO mice or CD4L mice was much
      lower than those from wild type mice. There was no difference between CD4KO and
      CD4L mice in T-cells expressing CD40 ligand after stimulation. Taken together,
      results in this study indicate that sCD4 suppresses IgG2a Ab responses of CD4L
      mice by inhibiting IFNgamma production. The mutant mice could provide a good
      model to analyze the mechanism of IFNgamma involvement in the Ab response against
      T-dependent Ag.

PMID- 11321127
TI  - Dietary fish oil increases CD8+ T-cells and decreases autoreactive T-cell
      activity in autoimmune NZB/W F1 mice.
AB  - To further elucidate the effect of different dietary fats on the pathogenesis of
      autoimmune diseases, five groups of New Zealand black/white (NZB/W) F1 mice were
      fed diets containing 200 g of different dietary fats including palm oil, lard
      soybean oil (1:1, w/w), soybean oil, canola oil or fish oil. Serum levels of anti
      DNA antibodies, proteinuria were followed every month and life span of the mice
      was determined. After 5 months of the respective diets, mice were killed at the
      age of 7 months and phenotypic analysis of splenic cells and peritoneal resident
      cells was performed. The pattern of production of cytokines in splenic T-cells
      was also investigated. The peritoneal resident cells were isolated for
      measurement of prostaglandin E2 (PGE2) levels. Significantly lower immunoglobulin
      G (IgG) anti-single-stranded DNA (ssDNA) and anti-double-stranded DNA (dsDNA)
      antibody levels were associated with less severe proteinuria and prolonged life
      span in mice fed dietary fish oil compared to mice fed other dietary oils.
      Phenotypic analysis of spleen cells showed increased CD8+ T-cells in the mice fed
      dietary fish oil compared to mice of the other dietary groups, and the percentage
      of natural killer (NK) cells in the mice fed dietary fish oil was also higher
      compared to the other dietary groups. The peritoneal resident cells produced
      lower PGE2 in mice fed fish oil compared to mice in the other dietary groups. To
      further investigate the effect of fish oil on autoreactive T-cells, splenic T
      cells purified using a nylon wool column were stimulated with non-T-cells of
      young NZB/W F1 mice. Our data suggest that the anti-DNA antibody augmentation
      ability of T-cells in mice fed dietary fish oil was significantly decreased
      compared to mice in the other dietary groups. These data indicate that dietary
      fish oil might maintain the existence of CD8+ T-cells, decrease autoreactive T
      cell activity and alleviate subsequent autoimmune processes in autoimmune prone
      NZB/W F1 mice.

PMID- 11321128
TI  - An outbreak of meningitis caused by Angiostrongylus cantonensis in Kaohsiung.
AB  - Eight Thai laborers developed meningitis after eating raw snails (Ampullarium
      canaliculatus) during the period from September 27 to October 6, 1998. The
      diagnosis of Angiostrongylus cantonensis infection was established in all
      patients by serologic studies of serum and cerebral spinal fluid (CSF). Clinical
      manifestations included meningitis, radiculitis and cranial nerve palsy. Symptoms
      included fever, headache, orbital pain, gastrointestinal upset, hyperesthesia,
      muscle weakness, skin rash and diplopia. Laboratory abnormalities included
      peripheral eosinophilia, CSF eosinophilia, transient elevation of liver enzymes
      and creatinine phosphokinase, elevation of IgE. No space occupying lesions were
      detected by magnetic resonance imaging of the brain. None of the patients
      developed severe sequelae during the 6-month follow-up except for occasional
      headache in one patient. This report also provides evidence that third stage
      larvae were present in the intermediate host, A. canaliculatus, which the
      laborers had eaten.

PMID- 11321129
TI  - Prevalence and relationship between allergic diseases and infectious diseases.
AB  - In order to determine the prevalence of childhood allergic diseases, infectious
      diseases, and the relationship between them, 8723 children from three junior high
      schools in Tou-Cheng City, Taipei County, were studied using questionnaires
      developed according to the International Study of Asthma and Allergies in
      Childhood (ISAAC) criteria combined with supplementary questions about infectious
      diseases. Students and their parents completed the questionnaires at home. The
      age of the children ranged from 10 to 18 years old (14.12 +/- 0.89 years), the
      majority (96.03%) was aged from 13 to 15 years old. The 12-month prevalences of
      self-reported allergic disease symptoms were: asthma symptom 8.2%, allergic
      rhinitis symptom 39.6%, and atopic dermatitis symptom 5.9%. The prevalences of
      diagnosis of the allergic diseases were: asthma 8.7%, allergic rhinitis 24.1%,
      and atopic dermatitis 3.9%. The 12-month prevalences of diagnosis of infectious
      diseases were: pneumonia 0.6%, bronchitis 7.2%, sinusitis 7.2%, purulent
      conjunctivitis 2.5%, otitis media 4.3%, encephalitis or meningitis 0.4%,
      gastroenteritis 14.5%, acne 23.9%, purulent dermatitis 1.3%, and other infectious
      diseases 1.2%. Lifetime admission rates of children due to infectious diseases
      were: pneumonia 1%, bronchitis 1.8%, sinusitis 0.3%, purulent conjunctivitis
      0.2%, otitis media 0.3%, encephalitis or meningitis 0.3%, gastroenteritis 2.1%,
      and other infectious diseases 0.6%. The prevalence of infectious diseases was
      significantly higher in children with allergic disease symptoms (defined as
      asthma, allergic rhinitis, or atopic dermatitis). These results demonstrated the
      presence of a link between allergic diseases and infectious diseases, which may
      have some important clinical implications.

PMID- 11321130
TI  - Efficacy of zafirlukast in the treatment of patients with bronchial asthma.
AB  - Zafirlukast is a drug newly used for the treatment of asthma. In this study, we
      examined the efficacy of zafirlukast on asthmatic patients and compared this
      efficacy between patients in different age groups and with different severities
      of pulmonary function. Patients concurrently inhaled long-acting beta2-agonist,
      corticosteroid or taken an oral aminophylline regimen, were treated with 20 mg
      oral zafirlukast twice daily for 6 weeks. In total, 32 asthmatic patients were
      included in the study. The primary efficacy measures included morning and evening
      peak expiratory flows (PEFs); secondary efficacy measures were the scoring of
      asthma symptoms including sleeping, coughing, and wheezing scores. Pulmonary
      functions including forced expiratory flow in 1 sec (FEV1), forced vital capacity
      (FVC), and PEF rate (PEFR) were examined during each clinical visit. Results
      showed that oral zafirlukast administration resulted in improvements in morning
      and evening PEFs and asthma symptom scores with the following statistical p
      values: morning PEF (285.8 vs 308.4 L/min), p = 0.003; evening PEF (293.3 vs
      312.1 L/min), p = 0.007; coughing score (1.03 vs 0.72), p = 0.011; and wheezing
      score (0.71 vs 0.51), p = 0.009. As to the pulmonary function during the clinical
      visit, only the improvement of PEFR reached a statistically significant level
      (74.3 vs 82, p = 0.017). We compared the efficacy between asthmatic patients of
      different ages and those with different severities of pulmonary function. In
      patients aged below 50 years, those with FEV1 above 80% of the predicted value
      and FVC above 85% of the predicted value were more responsive to zafirlukast. In
      conclusion, we demonstrate the efficacy of zafirlukast in asthma therapy
      particularly for those patients who are younger and have better pulmonary
      function. When asthmatic patients do not respond to inhaled corticosteroid, long
      acting beta2-agonist, or oral aminophylline, zafirlukast may provide an adjunct
      effect for asthma therapy.

PMID- 11321131
TI  - Ataxia telangiectasia: report of two cases.
AB  - Ataxia telangiectasia (A-T) is a rare autosomal recessive multisystem disease.
      The diagnosis of A-T is based on the typical clinical picture: ataxia and
      telangiectasia. However, an increase in (alpha-fetoprotein (AFP) level and the
      identification of the A-T mutated gene (ATM) assist in an early diagnosis. Here
      we report two cases of A-T diagnosed in our hospital (case 1: a 7-year-old boy;
      case 2: an 8-year-old girl). Both of these patients had typical clinical pictures
      of ataxia and telangiectasia, AFP was also increased (case 1:471.2 ng/dL; case 2:
      196 ng/dL). T-cell dysfunction was noted in both patients. Case 1 had IgG2
      deficiency and case 2 had IgA, IgG2 and IgG3 deficiency. Case 2 developed
      malignant lymphoma at 9 years of age and died of pneumonia with respiratory
      failure at 10 years of age. Because of rhe rarity of A-T in Taiwan, we report two
      cases to help pediatricians make an early diagnosis of A-T if they have a patient
      with progressive ataxia and oculocutaneous telangiectasia.

PMID- 11321132
TI  - Legionnaires' disease in a patient with rheumatoid arthritis.
AB  - A 62-year-old male with rheumatoid arthritis (RA) who was taking nonsteroid anti
      inflammatory drug for controlling synovitis developed a flare of his arthritis,
      hepatitis, and pneumonia due to infection with Legionella pneumophila serotype 1.
      Adult respiratory distress syndrome (ARDS) occurred following the development of
      pneumonia. After the introduction of erythromycin and ventilator support with
      positive end expiratory pressure (PEEP), his condition stabilized and he
      recovered gradually. We suggest that L. pneumophila should be considered early in
      the differential diagnosis of pneumonia in RA patients due to their
      immunocompromised status.

PMID- 11321133
TI  - Formation and regeneration of protoplasts for protease production in Streptomyces
      rimosus.
AB  - To improve the formation and regeneration frequency of protoplasts for protease
      production, experiments were performed using a cultivation of Streptomyces
      rimosus TM-55 (CCRC 940061) in a Tryptic-soy broth (TSB) containing 2% of glycine
      for 2 days. It was found that the protoplast formation decreased with increased
      incubation temperature and increased ratio of culture broth to vessel volume. The
      optimal incubation temperature was 28 degreesC and the ratio of culture broth to
      vessel volume was 2:5. The hypertonic medium containing 10 mM MgCl2, 25 mM CaCl2
      and 500 mM sucrose provided high stability for protoplasts. Supplementation with
      MgSO4, KCl and NaNO3 improved the regeneration frequency of protoplasts. The
      smear method had a higher protoplast regeneration frequency than the pour plate
      method. Protoplasts had protease productivity which was similar to that obtained
      with fresh mycelia, with each milliliter of culture broth yielding 141 units of
      protease with 3.5 x 10(8) protoplasts and 148 units of protease with 14.25 mg
      fresh mycelia respectively in a shaking culture, while the values were 15 and
      eight units of protease in a static culture.

PMID- 11321134
TI  - Pediatric rhegmatogenous retinal detachment.
AB  - PURPOSE: To review the clinical features and surgical and visual outcomes of
      pediatric rhegmatogenous retinal detachment (RRD) as seen in a tertiary referral
      center. METHODS: Retrospective case series spanning 6 years from January 1, 1991
      to January 1, 1997. Exclusionary criteria were trauma disrupting the globe and
      acute retinopathy of prematurity. RESULTS: The authors reviewed a series of 29
      eyes in 27 pediatric patients (birth to 18 years of age) with RRD. Seventy
      percent of the patients were male. The mean patient age was 9.6 years. Bilateral
      RRD was present in 22% of patients; 89% of patients had some form of bilateral
      ocular pathology at initial presentation. The two most common etiologies (34%
      each) were myopia and eyes that had undergone surgery for another ocular disorder
      with subsequent development of RRD. The most common presentation was decreased
      vision, with a mean duration of 52 days. At presentation, 75% of the affected
      eyes and 48% of the fellow eyes had visual acuity worse than 20/800. The most
      common type of retinal break was a horseshoe tear. Late diagnosis was a common
      problem, evidenced by the frequency of macular detachment (79%) and proliferative
      vitreoretinopathy (45%) at initial presentation. The most common primary repair
      was a scleral buckle. Anatomic reattachment was ultimately accomplished in 72% of
      cases with a mean of 2.2 surgeries per eye. Average postoperative follow-up time
      was 21.4 months (range 4 to 61 months). At final follow-up, 41% of the affected
      eyes had visual acuity 20/800 or better. Thirty-eight percent of the affected
      eyes had a final visual acuity better than or equal to the fellow eye.
      CONCLUSION: In this series, pediatric RRD occurred most commonly in association
      with myopia (Stickler's syndrome and adolescent retinopathy of prematurity) and
      prior intraocular surgery. Most eyes were anatomically reattached after multiple
      surgeries. Forty-one percent of eyes retained vision of 20/800 or better.
      Preserving vision in children with RRD is of great importance, particularly given
      the 89% frequency of vision-threatening abnormalities in fellow eyes.

PMID- 11321135
TI  - Results and complications of temporary silicone oil tamponade in patients with
      complicated retinal detachments.
AB  - BACKGROUND: To assess the results and complications of temporary silicone oil
      tamponade in the treatment of complicated retinal detachments. METHODS: Fifty
      eight consecutive eyes undergoing silicone oil removal were studied in a
      retrospective fashion. Forty-two eyes with proliferative vitreoretinopathy, nine
      eyes with giant tears, and seven traumatized eyes were included. In addition to
      anatomic and visual results, the following complications and their associated
      preoperative and intraoperative variables were assessed: glaucoma, hypotony, and
      keratopathy. RESULTS: Anatomic success was achieved in 81% of the eyes.
      Postoperative glaucoma was found in 12%, hypotony in 9%, and keratopathy in 7% of
      the eyes. Twenty-six (45%) of the 58 eyes had an increase in visual acuity of at
      least two Snellen lines after silicone oil removal. After multivariate logistic
      regression analysis for all variables versus the visual and anatomic results and
      versus the complications of glaucoma, hypotony, and keratopathy successively, a
      total of three or more operations (P < 0.05; odds ratio, 14.7) and the absence of
      an encircling band (P < 0.05; odds ratio, 29.9) were associated with
      redetachment, and a retinectomy size of more than 180 degrees was associated with
      hypotonia (P < 0.05; odds ratio, 67.5). CONCLUSIONS: Temporary silicone oil
      tamponade may be associated with a lower incidence of complications than recent
      studies have reported. Despite the acceptable risk of recurrent retinal
      detachment, the early removal of silicone oil may yield a lower rate of anterior
      segment complications and an increase in visual acuity in approximately half the
      eyes.

PMID- 11321136
TI  - Choroidal neovascularization in myopic eyes after laser-assisted in situ
      keratomileusis.
AB  - PURPOSE: To analyze the appearance and characteristics of choroidal
      neovascularization (CNV) in patients with high myopia corrected by laser-assisted
      in situ keratomileusis (LASIK). PATIENTS AND METHODS: The authors studied CNV in
      2955 consecutive eyes (1632 patients) that underwent LASIK for the correction of
      myopia (from -6 to -27.5 diopters). Follow-up was 34.2+/-11.3 months. RESULTS:
      Choroidal neovascularization occurred in three eyes (0.10%) and in one eye
      previous CNV was reactivated (three women, one man). The time interval between
      refractive surgery and CNV was 13+/-9.5 months (range, 4-26 months). Mean best
      corrected visual acuity (BCVA) after LASIK and before CNV development was 20/57
      (range, 20/100-20/29). After the appearance of CNV, mean BCVA was 20/606 (range,
      20/2000-20/80). Differences between BCVA before and after CNV were statistically
      significant (P = 0.04, paired Student's t-test). The CNV was treated in two cases
      by argon laser photocoagulation and in two cases by surgical excision of CNV by
      vitrectomy. The final mean BCVA was 20/277 (range, 20/800-20/50). Differences
      between BCVA after LASIK and after CNV treatment were statistically significant
      (P = 0.04, paired Student's t-test). CONCLUSIONS: Laser-assisted in situ
      keratomileusis as a correcting procedure for myopia was followed by low
      appearance of CNV. The appearance and treatment of CNV was followed by a
      significant decrease of BCVA.

PMID- 11321137
TI  - Polypoidal choroidal vasculopathy in Italy.
AB  - PURPOSE: To report on the frequency and clinical features of polypoidal choroidal
      vasculopathy (PCV) in a consecutive series of elderly Italian patients presenting
      with macular exudation. METHODS: The authors conducted a retrospective study on a
      series of 194 consecutive patients 50 years or older with newly diagnosed
      exudative maculopathy and the presumed diagnosis of age-related macular
      degeneration (ARMD). Color and/or red-free photographs and fluorescein and
      indocyanine green angiography were performed in all patients. RESULTS: Of the 194
      patients, 19 (9.8%) were diagnosed with PCV. The remaining 175 (90.2%) patients
      had ARMD complicated by choroidal neovascularization. No age or sex differences
      were observed between the two groups. The disease was unilateral in 103 (58.9%)
      of 175 ARMD cases compared with 15 (78.9%) of 19 PCV cases (P = 0.09). Nine
      (47.3%) of 19 patients with PCV had an extramacular choroidal neovascularization,
      compared with only 5 (2.9%) of 175 patients with ARMD (P < 0.0001). Significant
      drusen were present in the fellow eyes of 66 (64.1%) of 103 unilateral cases in
      the ARMD group and in 4 (26.7%) of 15 patients with unilateral disease in the PCV
      group (P = 0.006). CONCLUSIONS: Polypoidal choroidal vasculopathy is not an
      uncommon disease in Italy and should be suspected in patients presenting with
      extramacular lesions and no large drusen in the fellow eye.

PMID- 11321138
TI  - Dynamic observation of selective accumulation of a photosensitizer and its
      photodynamic effects in rat experimental choroidal neovascularization.
AB  - PURPOSE: The authors investigated the selective accumulation of a
      photosensitizer, ATX-S10(Na), in experimental choroidal neovascularization (CNV)
      in rats using a highly sensitive colorchromatic charge coupled device (CCD)
      camera. METHODS: To detect the development of experimental CNV in 30 rats, the
      animals were followed weekly with simultaneous fluorescein and indocyanine green
      angiography. After injecting ATX-S10(Na), the authors detected fluorescence from
      the photosensitizer using a highly sensitive color CCD camera. The camera was
      connected to a surgical microscope, under which rat fundi were observed through a
      coverglass in contact with the cornea. The retinas were excited with 405-435 nm
      light, and the light emitted from the photosensitizer passed through a 680-nm
      bandpass filter before being detected by the CCD camera. RESULTS: Immediately
      after injection, fluorescence appeared in the retinal vessels and then the entire
      retina. Thirty minutes postinjection, the intensity of the fluorescence was still
      strong from the whole retina, and the CNV was not detected. One hour after
      injection, retinal fluorescence was weak but still observable; 1.5 hours
      postinjection, retinal fluorescence was undetectable but fluorescence was strong
      from the CNV. Under the optimum therapeutic conditions, CNV was effectively
      occluded. CONCLUSION: ATX-S10(Na) selectively accumulates in the CNV in rats. The
      optimum therapeutic timing is approximately 1.5 hours postinjection of the dye in
      this CNV model.

PMID- 11321139
TI  - The clinical and ocular manifestations of Takayasu arteritis.
AB  - PURPOSE: To evaluate the clinical and ocular manifestations of Takayasu arteritis
      and the fundus fluorescein angiography (FFA) characteristics of Takayasu
      retinopathy (TR). PATIENTS AND METHODS: Medical records and fundus fluorescein
      angiograms of 156 eyes of 78 patients with Takayasu arteritis were reviewed.
      Fundus FA using a wide-field fundus camera (60 degrees) was performed in 19
      patients, and conventional angiography or spiral computed tomographic angiography
      was performed in all 78 patients. RESULTS: The series included 67 female and 11
      male patients; mean age at time of diagnosis was 26.7 years (range, 4-61 years).
      Hypertension was found in 44 (56.4%) patients, ischemic cerebrovascular symptoms
      in 18 (23.1%) patients, and amaurosis fugax in 20 (25.6%) patients. On fundus
      examination, no retinopathy was found in 87 (55.8%) eyes; hypertensive
      retinopathy was found in 48 (30.8%) eyes; and TR was found in 21 (13.5%) eyes.
      Patients with TR had carotid artery or aortic arch involvement, and patients with
      hypertensive retinopathy had involvement of the descending aorta or renal artery
      and sparing of the carotids. Best-corrected visual acuity in TR Stage 1 to 3
      ranged from 20/15 to 20/30, but in Stage 4, it ranged from 20/200 to hand motions
      because of secondary ocular complications. On FFA, the arm-to-retina circulation
      time was prolonged in all 21 eyes with TR (mean, 22.7+/-8.9 seconds), but only 14
      eyes showed delayed arteriovenous filling time, which was mainly found in
      chronic, moderate to severe TR, Stage 3 or 4. Arteriovenous anastomosis was found
      in all 12 eyes with Stage 3 and 4 TR. CONCLUSIONS: Delayed arm-to-retina
      circulation time is shown in all cases of TR, but delayed arteriovenous filling
      time is mostly found in moderate and severe TR. During ophthalmic examination,
      the delay of arteriovenous filling time and formation of arteriovenous
      anastomosis must be examined carefully to prevent visual deterioration.

PMID- 11321140
TI  - Presumed Eales' disease with neurologic involvement: report of three cases.
AB  - PURPOSE: To report three cases of presumed Eales' disease with neurologic
      lesions. METHODS: Case reports, systemic and neurologic evaluation, and magnetic
      resonance imaging. RESULTS: All three patients were young men who had seizures in
      the past; two had migrainous headache. Magnetic resonance imaging showed
      putaminal infarct in two cases and edema in the white matter of temporal cortex
      was noticed in one case. Clinical features in all these patients were suggestive
      of Eales' disease. CONCLUSION: Ischemic infarction of the brain can be seen in
      clinically suspected cases of Eales' disease.

PMID- 11321141
TI  - Sympathetic ophthalmia associated with pars plana vitrectomy without antecedent
      penetrating trauma.
AB  - PURPOSE: To evaluate, describe, and categorize the clinical presentation,
      clinical course, histopathology, and response to therapy in patients without a
      history of penetrating ocular trauma who developed sympathetic ophthalmia
      following pars plana vitrectomy. METHODS: The records of patients without a
      history of trauma who underwent pars plana vitrectomy and developed sympathetic
      ophthalmia were retrospectively reviewed. Cases were analyzed with respect to
      clinical presentation, fluorescein angiographic findings, anatomic and visual
      outcomes, histopathology, and response to therapy. RESULTS: Eight eyes were
      identified. The median age at presentation was 55 years, with a range of 14 to 62
      years. The time from vitrectomy to diagnosis of sympathetic ophthalmia ranged
      from 2 months to greater than 2 years, with a median of 7 months. Six of eight
      patients (75%) presented with anterior chamber reaction. All eight patients
      presented with a vitreous inflammatory response. The optic nerve was inflamed
      clinically or angiographically in four of eight cases (50%). Small yellow-white
      sub-retinal pigment epithelial deposits were present in four of eight cases
      (50%). Two eyes had lesions characterized as multifocal choroiditis. One eye had
      larger yellow placoid-like lesions. One eye presented with vitritis but no
      retinal lesions. Subretinal choroidal neovascularization was noted in the
      inciting eye of one patient. Vision improved in the sympathizing eye with
      immunosuppressive therapy in five of eight cases (62.5%). CONCLUSIONS:
      Sympathetic ophthalmia can be seen following pars plana vitrectomy in patients
      without penetrating injuries or a history of trauma. Indeed, it may be seen after
      successful vitrectomy for retinal detachment. Diverse clinical presentations are
      possible, and persistent or atypical uveitis following vitrectomy should alert
      the surgeon to the development of sympathetic ophthalmia.

PMID- 11321142
TI  - Hemodynamic changes in two patients with retinal circulatory disturbances shown
      by fluorescein angiography using a scanning laser ophthalmoscope.
AB  - PURPOSE: To assess hemodynamic changes in two patients with severely affected
      retinal circulation. METHODS: A 62-year-old man with central retinal artery
      occlusion and a 46-year-old woman with branch retinal vein occlusion were studied
      by fluorescein angiography with a scanning laser ophthalmoscope (SLO).
      Fluorescein angiography with SLO revealed hypofluorescent clumps of different
      sizes and hyperfluorescent dots in large retinal vessels. The velocities of the
      hypofluorescent clumps were calculated between two points on the same vessel, and
      movements of the hypofluorescent clumps and the hyperfluorescent dots were
      investigated. RESULTS: The velocities of the hypofluorescent clumps were slow and
      varied in the same vessel. The velocities of the hypofluorescent clumps increased
      at the sites with narrow calibers. The hypofluorescent clumps occasionally
      changed size in the bloodstream. The hypofluorescent clumps flowed along the
      walls of retinal vessels. Distance between consecutive hypofluorescent clumps was
      wide. Some vessels filled with hypofluorescent clumps were also detected. Rolling
      hyperfluorescent dots were seen in fluorescent plasma. CONCLUSIONS: The
      hypofluorescent clumps were concluded to be packed erythrocytes and the
      hyperfluorescent dots corresponded to leukocytes and platelets moving in the
      vessels. Fluorescein angiography with SLO is a useful method for evaluating
      hemodynamic changes using the hypofluorescent clumps in severely affected retinal
      circulation.

PMID- 11321144
TI  - Diagnostic and therapeutic challenges.

PMID- 11321143
TI  - Prevalence of factor V Leiden and activated protein C resistance in central
      retinal vein occlusion.
AB  - PURPOSE: Factor V Leiden is a common inherited mutation that is a significant
      risk factor for deep vein thrombosis. It results in resistance to activated
      protein C (APC). The association between factor V Leiden and central retinal vein
      occlusion (CRVO) remains controversial. This study was designed to determine the
      prevalence of APC resistance and the factor V Leiden mutation in patients with
      CRVO in a controlled study. METHODS: The study was designed as a case control
      study conducted in a tertiary care retina practice. The prevalence of APC
      resistance and factor V Leiden was determined by genetic testing of blood samples
      obtained from patients with CRVO and clinic control patients. RESULTS: Factor V
      Leiden was identified in 2.3% of patients with CRVO and 3.5% of clinic control
      patients. There was no significant association between the presence of factor V
      Leiden and CRVO (odds ratio, 1.13; 95% confidence interval, 0.65-1.98; P = 0.66).
      CONCLUSION: Factor V Leiden does not appear to be associated with CRVO. Routine
      screening of patients with CRVO does not appear to be warranted.

PMID- 11321145
TI  - Transient appearance of classic choroidal neovascularization after transpupillary
      thermotherapy for occult choroidal neovascularization.

PMID- 11321146
TI  - Bilateral choroidal neovascularization after laser-assisted in situ
      keratomileusis.

PMID- 11321147
TI  - Transient improvement in visual acuity and macular edema in central retinal vein
      occlusion accompanied by inflammatory features after pulse steroid and anti
      inflammatory therapy.

PMID- 11321148
TI  - Ischemic central retinal vein occlusion and retinitis pigmentosa: lower risk of
      neovascularization?

PMID- 11321149
TI  - Evolution of distinct chorioretinal scars in recurrent MEWDS.

PMID- 11321150
TI  - Late recurrence and choroidal neovascularization in multiple evanescent white dot
      syndrome.

PMID- 11321151
TI  - Disappearance of soft drusen following macular hole surgery.

PMID- 11321152
TI  - Spontaneous resolution of small stage 3 and 4 full-thickness macular holes viewed
      by optical coherence tomography.

PMID- 11321153
TI  - A simple noncontact wide-angle fundus photography procedure for clinical and
      research use.

PMID- 11321154
TI  - Intravitreal injection of tissue plasminogen activator and gas in subretinal
      hemorrhage caused by age-related macular degeneration.

PMID- 11321155
TI  - Dense premacular hemorrhage from a retinal macroaneurysm treated by argon laser.

PMID- 11321156
TI  - Silastic infusion trochar.

PMID- 11321157
TI  - New instruments for intraocular lens manipulation via the pars plana.

PMID- 11321158
TI  - Intrusion of a scleral buckle: a late complication of retinal reattachment
      surgery.

PMID- 11321159
TI  - Strategy for increased efficiency of transfection in human cell lines using radio
      frequency electroporation.
AB  - Traditional electroporation devices use direct current electric fields to
      stimulate the uptake of oligonucleotides, plasmids, short peptides, and proteins
      into a variety of cell types. A variation of this widely used technique is now
      available which relies on radio frequency (RF) electrical pulses. This
      oscillating type of electrical field reportedly elicits greater uptake of plasmid
      DNA across the plasma membrane. We evaluated a protocol for RF electroporation of
      the a human embryonic kidney cell line and a Burkitt's lymphoma (BL) cell line
      for effeciency of transfection by RF electroporation. The plasmid EGFP, which
      codes for the widely used fusion protein, enhanced green fluorescent protein
      (EGFP), was used as a reporter of plasmid uptake after transfections.
      Transfection efficiency consistently increased approximately 30% from that
      typically obtained with conventional DC type electroporation and was accompanied
      by greater survivability of cells. Additionally, in some instances, percent
      transfection efficiency increased to over 70%. Thus, RF electroporation
      represents an improved methodology for transfection of human cell lines.
      Moreover, the RF protocol is simple to incorporate in laboratories already
      utilizing conventional electroporation devices and techniques.

PMID- 11321160
TI  - Heterologous gene expression in bacterial systems under reduced oxygen tensions.
      Small-scale optimization precedes industrial fermentation.
AB  - The expression of heterologous fusion proteins from the anaerobically inducible
      Escherichia coli nitrite reductase nirB promoter has been described using a
      number of different industrial regimes, but which have proved impractical for
      scaling down to suit primary research purposes. This paper describes the novel
      application of microbiological gas sachets generating anaerobic and
      microaerophilic environments to evaluate the inducible expression under the
      influence of nirB of heterologous proteins by attenuated vaccine strains of
      Salmonella typhimurium. The conditions of reduced oxygen tension model those
      found in lymphoid organs colonized by Salmonella in vivo and so can be used to
      optimize the vaccine dose prior to administration. Modeling in vivo promoter
      inducibility to monitor the stability of a plasmid within attenuated vaccine
      strains of bacteria offers an attractive alternative to antibiotic resistance,
      which is not permitted for clinical use in humans. This technological advance may
      be utilized to optimize heterologous gene expression in any microaerophilic
      bacterial system as a pilot, prior to production-scale applications.

PMID- 11321161
TI  - The effect of KSCN on the partition of proteins in polyethylene glycol/(NH4)2SO4
      aqueous two-phase system.
AB  - The effect of potassium thiocyanate on the partitioning of lysozyme and BSA in
      polyethylene glycol 2000/ammonium sulfate aqueous two-phase system has been
      investigated. As a result of the addition of potassium thiocyanate to the
      PEG/ammonium sulfate system, the PEG/mixed salts aqueous two-phase system was
      formed. It was found that the potassium thiocyanate could alter the pH difference
      between the two phases, and, thus, influence the partition coefficients of the
      differently charged proteins. The relationship between partition coefficient of
      the proteins and pH difference between two phases has been discussed. It was
      proposed that the pH difference between two phases could be employed as the
      measurement of electrostatic driving force for the partitioning of charged
      proteins in polyethylene 2000/ammonium sulfate aqueous two-phase system.

PMID- 11321162
TI  - Carbonic anhydrase from bovine bone.
AB  - In this research, carbonic anhydrase enzyme, which was taken from the bones of an
      animal, was purified and characterized for the first time. For this, the bones of
      a young cow were used. The purification treatment was completed in three steps.
      Three different isoenzymes, such as peripheral, cystolic, and integral from the
      bone-cell cytozolic isoenzyme were purified and characterized. In purification of
      the three isoenzymes, the technique of affinity chromatography, which utilized
      Sepharose-4B-L-Tyrosine-Sulphanylamide, was used. In measuring the activities of
      enzymes, two different methods were applied. These are the esterase methods that
      utilize hydratase and p-nitrophenylacetate as substrate. The measurement of
      proteins was done with the methods of Bradford and Coomassie Brillant Blue. The
      optimum pH and temperature of each enzyme were measured and molecular weights
      were measured by gel-filtration. Its purity was examined by SDS-PAGE (3-10%
      alternating) electrophoresis and the inferior unit was defined. The inhibition
      effects of some chemicals were tested for each of the three isoenzymes.

PMID- 11321163
TI  - Expression of anti-neuroexcitation peptide (ANEP) of scorpion Buthus martensii
      Karsch in Escherichia coli.
AB  - According to the cDNA sequence of anti-neuroexcitation peptide of scorpion Buthus
      martensii Karsch, the putative mature anti-neuroexcitation peptide (ANEP)
      encoding DNA fragment was obtained by a PCR method, then was cloned into
      expression plasmid pET28a, fused with His tag at its 3' end. When expressed in E.
      coli BL21 (DE3), the expression of recombinant ANEP was 15% of total cellular
      proteins, while most recombinant ANEP products existed in the form of insoluble
      inclusion bodies. Coexpression of molecular chaperones or protein disulfide
      isomerase could not improve its solubility. The recombinant ANEP in the cell
      lysate was purified to homogeneity by metal chelating affinity chromatography and
      Superdex 30 chromatography. In bioassay with convulsive mice model induced by
      thiosemicarbazide, recombinant ANEP could apparently delay the convulsion seizure
      of model animals by 18% and showed anti-neuroexcitatory activity.

PMID- 11321165
TI  - Chemoenzymatic synthesis of surfactants from carbohydrates, amino acids, and
      fatty acids.
AB  - The chemoenzymatic synthesis of new surfactants is reported; they were prepared
      from unprotected carbohydrates, amino acids, and fatty acids. This study pointed
      out the factors that govern the possibility to enzymatically bind the
      carbohydrate to the amino acid.

PMID- 11321164
TI  - Polyethylene glycol enhanced refolding of the recombinant human tissue
      transglutaminase.
AB  - Tissue transglutaminase forms cross-links between lysine and glutamine side
      chains of polypeptide chains in a Ca2+-dependent reaction; its structural basis
      is still not clarified. In this study, we demonstrate that the refolding of the
      human recombinant enzyme molecule to its catalytically active form from inclusion
      bodies needs the presence of a helper material with higher molecular mass, but
      only in the initiation phase. Ca2+ and nucleotides are ascribed as affector
      molecules also in the early phase of structural reconstitution. Two optimal
      concentrations of polyethylene glycol and a relatively long time scale for the
      evolution of the final structure were identified. The optimized refolding
      procedure is reported.

PMID- 11321166
TI  - Consultant medical manpower.

PMID- 11321167
TI  - Lung cancer detection: a new challenge for Irish medicine.

PMID- 11321168
TI  - In defence of the single case report.

PMID- 11321169
TI  - Hypoglycaemic episodes in children with insulin dependent diabetes mellitus--can
      the frequency or severity be reduced?
AB  - To ascertain if significant hypoglycaemic episodes can be avoided or managed more
      appropriately in children with insulin dependent diabetes mellitus (IDDM). A
      retrospective chart audit was performed on all children with IDDM admitted with
      hypoglycaemia between 1.1.90 and 31.8.97. Of the 21 children studied, 9 presented
      with seizures and 1 with coma. In 9 the hypoglycaemia was unexplained. Only 6
      parents used glucagon. Five children were readmitted during the review with a
      further hypoglycaemic episode. Four of these had their first admission
      significantly sooner after diagnosis than those without recurrent episodes.
      Hypoglycaemic episodes are often unexplained and are unlikely to be completely
      avoidable. Improved support services during intercurrent illness may reduce the
      frequency of some hypoglycaemic episodes and increased use of glucagon at home
      may reduce the severity of some. Children who have their first hypoglycaemic
      episode within one year of diagnosis are at risk of having recurrent episodes.

PMID- 11321170
TI  - A critical appraisal of the out-patient fracture clinic: is communication really
      the key?
AB  - The most common factor in an adversarial doctor-patient relationship is failed
      communication. We audited our communication skills, patient satisfaction and
      assessed patients' capacity for retaining information. 120 consecutive first time
      patients with one of 5 fracture types were assessed. Patients scored (a) the
      doctor's communication skills and (b) their overall fracture clinic experience.
      Patient satisfaction was high, mean 8.2 (range 2-10, SD 1.76) points. There was a
      statistically significant difference in a patient's knowledge pre and post
      consultation. Forty-three patients (36%) could recall a specific consequence of
      the fracture (p<0.005). Forty (31%) and twenty six (22%) patients could recall
      the name of the Registrar and Consultant respectively. Doctors scored 9.2 (range
      7-10, SD 1.23) points for communication skills. Patients are concerned with a
      fracture's impact on daily activities, often failing to register who treats them
      and any serious consequences. With doctors being scored so highly, the dilemma
      remains of how better to deliver the message.

PMID- 11321171
TI  - Nutrition and lifestyle survey of 15-17 year old second level school pupils in
      the Cork city area.
AB  - This study deals with the dietary intakes of a representative sample of Cork city
      area, school-going children, aged 15-17 years (n=125). Dietary intake was
      assessed by diet history with published food portion sizes to estimate size.
      Background data and information on lifestyle were collected by means of a
      questionnaire. Results indicate that, in general, the study group was reasonably
      well nourished. However, fat consumption (40%) was higher than the target of <35%
      for energy intake, for both males and females, and saturated fat intake (15%) was
      also above the 10% of energy guideline. The percentage of energy derived from
      carbohydrate (45%) was below the guideline value of 50% for energy intake for
      males and females. Relatively low iron, calcium and folate intakes were found for
      females. Smoking was more prevalent among females than males. Alcohol consumption
      among females was higher than among males. Even though all students participated
      in some physical activity, less females participated in high activity sport.
      Based on these results, some concern about the dietary habits and the related
      health consequences in Cork adolescents appears justified.

PMID- 11321172
TI  - Efficacy of pulmonary rehabilitation in an Irish population.
AB  - This study evaluated the results after 8 and 52 weeks of a comprehensive
      pulmonary rehabilitation programme for patients with chronic obstructive
      pulmonary disease (COPD) in Ireland. 170 patients with clinical and physiological
      evidence of COPD (mean FEV1 43.1 +/- 17.0%pred.) were recruited into an 8 week
      programme. At the time of final evaluation 15 patients had died, 25 patients had
      not been compliant with required attendances and 1 patient had transferred to
      another programme. To date assessments of 106 of the remaining 129 patients were
      made after eight weeks and of 78 patients after 1 year. Assessment consisted of
      pulmonary function testing; exercise tolerance as measured by a progressive
      maximal walking test (shuttle walk test) and an endurance test (treadmill test);
      quality of life (QoL) as measured by the Chronic Respiratory Disease
      Questionnaire (CRDQ), the St. George's Hospital Questionnaire (SGHQ) and the
      Breathing Problems Questionnaire (BPQ); and perceived dyspnoea on the Borg scale.
      Significant improvements in exercise tolerance, (shuttle p<.001, treadmill
      p<.001), QoL, (BPQ p<.001, CRDQ p<.001, SGHQ p<.001) and dyspnoea (p<.001) were
      demonstrated after 8 weeks. These improvements were maintained at 1 year. These
      results suggest that pulmonary rehabilitation can increase exercise tolerance and
      improve QoL in patients with COPD.

PMID- 11321173
TI  - A study of the use of aspirin by general practitioners in suspected myocardial
      infarction.
AB  - Aspirin's role in the management of suspected myocardial infarction has been well
      established. The general practitioner is in an ideal position to administer this
      well proven therapy to suitable patients. This study investigates the extent of
      use of aspirin by general practitioners in the acute setting in a rural area in
      the West of Ireland. It comprises two parts. Part one is a prospective survey of
      all patients referred to Roscommon County Hospital by their G.P. in a four month
      period with a complaint of chest pain (n=76). Details were taken regarding the
      characteristics of the pain, use of referral letter, presence of risk factors for
      ischaemic heart disease and pre-hospital administration of drugs, including
      aspirin. Part two is a telephone survey of the G.P.s in the referral area. They
      were asked whether they carried each of six common drugs, including aspirin, in
      their doctor's bag. Less than two thirds of G.P.s contacted carried aspirin
      routinely in their bag and less than 10% administered aspirin in patients with
      chest pain highly suspicious of cardiac ischaemia. Discussion includes a review
      of relevant recent literature and exploration of possible reasons for the
      results.

PMID- 11321174
TI  - Posterior fossa tumours in childhood: evaluation of presenting clinical features.
AB  - A retrospective review was performed of the age profile and clinical features at
      presentation of 79 children with posterior fossa tumours. The mean age at
      presentation in this series (6.6 years) is consistent with a decreasing trend
      over the past 70 years. Headaches, ataxia and torticollis emerge as significant
      symptoms worthy of further investigation whilst abdominal pain and constipation
      might herald the presence of a posterior fossa tumour on rare occasions.

PMID- 11321175
TI  - Severe HELLP syndrome remote from term.
AB  - A 27 year-old nulliparous woman was admitted to University College Hospital
      Galway with severe preeclampsia at 21 weeks 'gestation. In addition, there was
      evidence of HELLP syndrome with renal failure. A decision was made to end the
      pregnancy to save the mother's life. Labour was induced with misoprostol and
      vaginal delivery of a male stillborn fetus weighing 250 g was achieved after 19
      hours. The condition of the patient improved gradually following delivery. Renal
      impairment, however, persisted postpartum. HELLP syndrome is a life-threatening
      complication of pregnancy which can only be cured by delivery. Other therapeutic
      modalities are only palliative but may improve the outcome for the very premature
      viable fetus. Conservative management is not an option when HELLP syndrome occurs
      long before fetal viability has been reached.

PMID- 11321176
TI  - Incisional hernia following supra-pubic catheterisation.

PMID- 11321177
TI  - Acute lymphoblastic leukemia: a diagnosis easily missed.

PMID- 11321178
TI  - Hepatitis B vaccine uptake in a high risk hospital population.

PMID- 11321179
TI  - Exaggerated claims do not help consultants' cause.

PMID- 11321180
TI  - A pilot case-control study of zidovudine compared with zidovudine plus didanosine
      in patients with advanced HIV-1 disease and no previous experience with
      antiretrovirals.
AB  - Although zidovudine (ZDV) is effective in HIV-1-infected patients, the duration
      of its efficacy may be short when treatment is started in advanced HIV disease.
      This pilot prospective case-control study was designed to evaluate the
      combination of ZDV plus didanosine [ddI] compared with ZDV monotherapy as an
      initial therapeutic strategy. 'Control' patients (ZDV monotherapy) were matched
      with 'case' patients (ZDV plus ddI combination therapy) according to the presence
      or absence of AIDS-defining criteria at entry and CD4 cell count. The case
      patient group consisted of 35 consecutive HIV-1-infected individuals with < or =
      300 CD4 cells/mm3, no previous experience of antiretroviral therapy and who
      accepted treatment with a combination of ZDV plus ddI. The control patient group
      consisted of 35 consecutive patients with similar characteristics, but who
      preferred to start treatment with ZDV alone. Control patients received 250 mg ZDV
      bid and case patients received ZDV at the same dose plus ddI (200 mg bid).
      Primary study endpoints were virological (serum HIV-1 RNA) and immunological (CD4
      cell count) responses. Viral phenotype (syncytium-inducing (SI) or non-syncytium
      inducing (NSI)), development of mutations at codons 215, 41 and 74 and clinical
      progression (new AIDS-defining event or death) were also assessed. Virological
      and CD4 cell count responses were significantly greater and more sustained in the
      group treated with ZDV plus ddI than in the control group, with peak responses of
      -1.2 +/- 0.7 log10 versus -0.3 +/- 0.4 log10 at 1 month (P = 0.0003) and 61 +/-
      52 cells/mm3 versus 19 +/- 25 cells/mm3 at 2 months (P = 0.001), respectively. In
      both groups the percentage of patients developing a mutation at codon 215 was
      around 80 per cent at 12 months. A mutation at codon 74 was detected in 30 per
      cent of case patients at 12 months. Five case patients (14 per cent) versus 12
      control patients (34 per cent) showed signs of clinical progression (P = 0.09).
      In a multivariate model, clinical progression was significantly associated with a
      baseline

PMID- 11321181
TI  - Antiretroviral therapy and clinical trials: what now?

PMID- 11321182
TI  - Nucleoside analogues and other investigational modalities for the treatment of
      chronic hepatitis B.

PMID- 11321183
TI  - Synergy, activity and tolerability of zidovudine and interferon-alpha in patients
      with symptomatic HIV-1 infection: AIDS Clincal Trial Group 068.
AB  - Thirty-four subjects with symptomatic HIV-1 infection, p24 antigenaemia, and CD4
      cell counts > 200/mm3 were randomly assigned to receive treatment with either
      zidovudine (ZDV) orally, interferon-alpha (IFN-alpha) subcutaneously, or both at
      respective low (200 mg ZDV/ 2 million international units IFN-alpha (MIU)),
      middle (400 mg/4 MIU) or high (600 mg/6 MIU) daily dose levels for 12 weeks.
      Thereafter, all patients received combination therapy at the initially assigned
      dose level to a total of 96 weeks. This design permitted analysis by the
      combination index (CI) method, which demonstrated antiretroviral synergy between
      ZDV and IFN-alpha with respect to p24 antigen suppression. Over the first 12
      weeks, combination therapy was acceptably tolerated, more so than IFN-alpha
      monotherapy, and it was significantly more active in suppressing antigenaemia
      than either of the monotherapies. Similarly, the high-dose combination was the
      most active dose level over weeks 12 to 96. Combination ZDV/IFN-alpha at the
      optimal dose level defined by this trial merits further study. In addition, the
      CI design strategy employed here may be useful for the investigation of new
      antiretroviral combinations.

PMID- 11321184
TI  - Tolerability and activity of a new recombinant interferon-alpha B/D hybrid in
      patients with HIV-1 infection.
AB  - The maximum tolerated dose (MTD) and toxicity profile of a new recombinant
      interferon-alpha B/D hybrid (IFN-alpha B/D) in HlV-1-infected patients were
      determined in an outpatient, dose-escalating study with dose groups of three
      patients: 16, 32, 48, 64, 96 and 112 million international units (MIU) three
      times weekly subcutaneously during 12 weeks. The MTD was the last dose level just
      below the dose level at which more than one patient experienced > or = grade 3
      toxicity. The study also searched for preliminary evidence of efficacy of IFN
      alpha B/D. Sixteen HIV-1-infected patients with CD4 cell counts > or = 200/mm3
      were enrolled: eight were asymptomatic and eight had symptomatic disease. Two
      patients were excluded as a result of protocol violations. Five patients (36 per
      cent; one at each tested dose level) discontinued prematurely due to side
      effects. One patient was lost to follow-up. Twelve patients (87 per cent)
      experienced > or = grade 2 toxicity. Toxicity > or = grade 3 occurred in none of
      three patients assigned to 16 MIU, one of five assigned to 32 MIU (fatigue), one
      of three assigned to 48 MIU (haemorrhagic colitis) and two of three assigned to
      64 MIU (fatigue). One patient (48 MIU) had reversible cardiomegaly. Progressive
      weight loss was experienced by 12 of 14 participants. Serum HIV-1 p24 antigen
      declined in nine of 11 antigenaemic patients (seven persistently > 50 per cent)
      without a clear dose-response relationship. CD4 percentages showed no consistent
      pattern and T cell reactivity diminished. The tolerability and toxicity profile
      of IFN-alpha B/D appear to be fairly similar to that of other types of IFN-alpha.

PMID- 11321186
TI  - Millennium reflections.

PMID- 11321185
TI  - Resistance to (-)-2',3'-dideoxy-3'-thiacytidine (3TC) in HIV-1 isolated from
      paediatric patients.
AB  - We conducted detailed virological evaluations of 16 HIV-1-infected paediatric
      patients treated with 3TC (lamivudine) monotherapy. High-level phenotypic
      resistance against this compound (up to 2,500-fold) was seen in virtually all
      cases, usually within 8-12 weeks of initiation of therapy. This was concomitant
      with the appearance of the M184V mutation in viral reverse transcriptase,
      previously shown to be responsiblefor such resistance. Viral burden fell in
      virtually all cases after commencement of therapy, and remained below baseline in
      each instance studied, despite a rebound effect and the appearance of drug
      resistance. Viral isolates from some patients underwent a switch from a non
      syncytium-inducing (NSI) to a syncytium-inducing (SI) phenotype during the course
      of the study, although no relationship was apparent between dose of drug
      employed, time to development of drug resistance or time of appearance of SI
      phenotype.

PMID- 11321187
TI  - Chlamydia pneumoniae in multiple sclerosis: humoral immune responses in serum and
      cerebrospinal fluid and correlation with disease activity marker.
AB  - Humoral immune responses to Chlamydia pneumoniae (C. pneumoniae) were studied in
      paired sera and cerebrospinal fluid (CSF) of patients with definite multiple
      sclerosis (MS) and other inflammatory and non-inflammatory neurological diseases.
      Seropositivity was not significantly different between these groups. However, C.
      pneumoniae-specific IgG titers were significantly higher in CSF of MS than in
      controls. Sixteen out of 52 seropositive MS patients (30.8%) showed intrathecal
      synthesis of C. pneumoniae-specific IgG but only one of 43 seropositive controls
      (2.3%). In MS, this was strongly associated with intrathecal synthesis of
      polyclonal IgG in 13/16 patients. However, these elevated C. pneumoniae antibody
      titers in CSF did not significantly correlate with disease duration, disease
      course, clinical or MRI disease activity, disability or presence of oligoclonal
      IgG in MS.

PMID- 11321188
TI  - Raised cerebrospinal fluid nitrite and nitrate levels in patients with multiple
      sclerosis: no correlation with disease activity.
AB  - A growing body of evidence implicates excessive generation of nitric oxide (NO)
      within the central nervous system (CNS) in multiple sclerosis (MS). The aim of
      our study is to analyse nitrite and nitrate as end products of NO in the
      cerebrospinal fluid (CSF) from MS patients and correlate the concentrations with
      clinicol characteristics of the disease. CSF nitrite and nitrate concentrations
      were measured after reduction of nitrate, by Griess reaction, in 105 MS potients,
      27 patients with non-inflammatory neurological disorders (NIND) and 13
      individuals without neurological disorder (Co). Mean CSF nitrite and nitrate
      concentrations were significantly higher in patients with MS and NIND compared
      with the Co patients (9.44 and 8.68, respectively, versus 6.85 microM; P=0.0001
      and P=0.031, respectively). There was no significant correlation between CSF
      nitrite and nitrate concentrations and activity, phase, severity and duration of
      MS. Our data are in agreement with the results of previous studies which have
      demonstrated raised concentrations of CSF NO metabolites in MS patients,
      providing further evidence for NO involvement in MS. The lack of correlation
      between NO metabolites and disease activity speaks in favour of the possible dual
      role of NO, as both immunoregulatory and pro-inflammatory molecule, in the
      pathogenesis of MS.

PMID- 11321189
TI  - The predictive value of gadolinium enhancement for long term disability in
      relapsing-remitting multiple sclerosis--preliminary results.
AB  - As short-term MRI studies are increasingly being used to monitor disease activity
      in multiple sclerosis (MS) it is vital to establish if short-term MRI activity is
      predictive of long term clinical outcome. We followed up after 5 years a group of
      10 benign (relapsing-remitting MS with a disease duration > 10 years and EDSS <
      or = 3) and 10 early relapsing-remitting patients who previously had monthly
      serial MRI scans for 6 months. In the early relapsing-remitting group median EDSS
      at entry to the initial serial study was three and in the benign group 2.5. At 5
      year follow up, five of these 20 patients had developed a definite deterioration
      in EDSS. The median number of new enhancing lesions detected originally in the
      group that had deteriorated was 11 (7-17) compared to 0 (0-5) new enhancing
      lesions, for those who had not deteriorated (P < 0.05). There was a trend towards
      a higher baseline T2 lesion load in the group with a definite change in EDSS but
      this was not significant This study suggests that short-term measurement of the
      number of gadolinium enhancing lesions may predict long term outcome in relapsing
      remitting MS.

PMID- 11321190
TI  - Intra-observer, inter-observer and inter-scanner variations in brain MRI volume
      measurements in multiple sclerosis.
AB  - INTRODUCTION: Measurement of brain volume on magnetic resonance imaging (MRI)
      scans is regarded as an objective marker of multiple sclerosis (MS) severity with
      the potential to monitor treatment efficacy accurately. This study was performed
      to assess the variability of brain MRI volume measurements. PATIENTS AND METHODS:
      We studied nine patients with relapsing-remitting MS, who were imaged on two
      occasions (separated by an interval of 24 h) using two different MR scanners and
      fast fluid-attenuated inversion recovery (fast-FLAIR) sequences. The whole brain
      volume computed from each image was measured three times by three observers using
      a seed-growing technique based on signal intensity thresholding. Intra-observer,
      inter-observer and inter-scanner variabilities were expressed as coefficients of
      variations (COVs). The inter-scanner variability included not only the intra
      observer variation but also the repositioning variability and the variation in
      observed brain volume caused by different scanner hardware and sequence
      implementations. RESULTS: There was no statistically significant difference in
      patients' brain volume values between observers (P=0.82) or between scanners
      (P=0.30). The mean intra-observer COV was 1.2% (s.e.=0.4%), the mean inter
      observer COV was 1.8% (s.e.=0.8%) and the mean inter-scanner COV was 2.4%
      (s.e.=1.2%). The intra-observer variance was not statistically different from
      those found between observers (P=0.83) or scanners (P=0.44). CONCLUSION: The
      intra-observer variability in brain volume measurements found in this study was
      within the range of intra-observer variability found in previous studies. This
      study shows that the use of different observers and MR scanners has only a small
      influence on the measured brain volume and does not affect the reproducibility of
      this measurement greatly.

PMID- 11321191
TI  - A meta-analysis of genomic screens in multiple sclerosis. The Transatlantic
      Multiple Sclerosis Genetics Cooperative.
AB  - We combined the raw genotyping data from three large multiple sclerosis genome
      screens and performed a global meta-analysis in order to compare and summarize
      the linkage results from the different studies. In alphabetical order, the
      screens provided data from 442 markers typed in 52 multiplex families with a
      total of 133 affected individuals (the American screen), 314 markers typed in 128
      families with 264 affecteds (the British screen) and 257 markers typed in 61
      families with a total of 139 affected subjects (the Canadian screen). Multipoint
      analysis of these data was performed using the GENEHUNTER program. The highest
      non-parametric linkage (NPL) score in the meta-analysis was observed on
      chromosome 17q11 (NPL score 2.58), although this score falls short of genome-wide
      significance. A total of eight regions had NPL scores greater than 2.0. One of
      the regions with an NPL score greater than 2.0 was the HLA region on chromosome
      6p21 (NPL=2.2). This region is known, from association studies, to be involved in
      MS susceptibility, but the modest linkage result observed here suggests the
      encoded susceptibility effect is not large compared with the high familial
      recurrence in MS (lambda approximately 20). Overall, our linkage results suggest
      that MS is likely to be multigenic in its genetic susceptibility.

PMID- 11321192
TI  - United States open-label glatiramer acetate extension trial for relapsing
      multiple sclerosis: MRI and clinical correlates. Multiple Sclerosis Study Group
      and the MRI Analysis Center.
AB  - After the placebo-controlled extension of the pivotal US trial of glatiramer
      acetate for the treatment of relapsing multiple sclerosis ended, 208 participants
      entered an open-label, long-term treatment protocol Magnetic resonance imaging
      (MRI) was added to the planned evaluations of these subjects to determine the
      consequences of long-term treatment on MRI-defined pathology and evaluate its
      clinical correlates. Of the 147 subjects that remained on long-term follow-up,
      adequate images were obtained on 135 for quantitative MRI analysis. The initial
      imaging sessions were performed between June 1998 and January 1999 at 2,447 +/-
      61 days (mean +/- standard deviation) after the subject's original randomization.
      Clinical data from a preplanned clinical visit were matched to MRI within 3 +/-
      51 days. At imaging, 66 patients originally randomized to placebo (oPBO) in the
      pivotal trial had received glatiramer acetate for 1,476 +/- 63 days, and 69
      randomized to active treatment with glatiramer acetate (oGA) were on drug for
      2,433 +/- 59 days. The number of documented relapses in the 2 years prior to
      entering the open-label extension was higher in the group originally randomized
      to placebo (oPBO=1.86 +/- 1.78, oGA=1.03 +/- 1.28; P=0.002). The annualized
      relapse rate observed during the open-label study was similar for both groups
      (oPBO=0.2 7, +/- 0.45 oGA=0.28 +/- 0.40), but the reduction in rate from the
      placebo-controlled phase was greater for those beginning therapy with GA (oPBO
      reduced by 0.66 +/- 0.71, oGA reduced by 0.23 +/- 0.58; P=0.0002). One or more
      gadolinium enhancing lesions were found in 27.4% of all patients (number of
      distinct enhancements=1.16 +/- 2.52, total enhanced tissue volume=97 +/- 26
      microl). The risk of having an enhancement was higher in those with relapses
      during the open-label extension (odds ratio 4.65, 95% confidence interval (CI)
      2.0 to 10.7; P=0.001). The odds for finding an enhancement was 2.5 times higher
      for those patients originally randomized to placebo (CI 1.1 to 5.4; P=0.02)
      compared to those always on glatiramer acetate. MRI-metrics indicative of chronic
      pathology, particularly measures of global cerebral tissue loss (atrophy), were
      uniformly worse for those originally on placebo. These observations enrich our
      long-term follow up of the clinical consequences of treatment with glatiramer
      acetate to include its apparent effects on MRI-defined pathology. They show that
      the effect of glatiramer acetate on enhancements is definite, but modest,
      consistent with the drug's described mechanisms of action, and that a delay in
      initiating treatment results in progression of MRI-measured pathology that can be
      prevented.

PMID- 11321193
TI  - Long-term therapy with glatiramer acetate in multiple sclerosis: effect on T
      cells.
AB  - Glatiramer acetate (GA) is an immunotherapeutic drug for multiple sclerosis (MS).
      Several mechanisms of action have been demonstrated which target and affect T
      cells that are specific for myelin antigen epitopes. We measured the in vitro
      proliferation of GA-responsive T-cells from untreated MS patients and from normal
      healthy subjects; in addition, we determined the effect of prolonged GA therapy
      or interferon-beta therapy on the in vitro proliferation of GA-responsive T-cells
      of MS patients. We found that GA induces the proliferation of T-cells isolated
      from individuals who have not been previously exposed to GA, and that long-term
      in vivo therapy of MS patients with GA abrogates the GA-induced proliferative
      response of T-cells. In GA-treated patients, there is no evidence of generalized
      immunosuppression; both tetanus toxoid and anti-CD3 induced proliferative
      responses remain unaffected. We propose that prolonged in vivo exposure to GA may
      result in the eventual induction of anergy or deletion of a population of GA
      responsive cells that may also be T-cells that are pathogenic in MS. This
      mechanism of action, in addition to other mechanisms that have been demonstrated,
      suggests that GA has pleiotropic effects on the immune system in MS.

PMID- 11321194
TI  - Interferon beta-1b and intravenous methylprednisolone promote lesion recovery in
      multiple sclerosis.
AB  - OBJECTIVE: To determine whether lesion evolution in relapsing-remitting multiple
      sclerosis (RRMS) patients is altered by treatment with interferonbeta1b (IFNbeta
      1b) or by intravenous methylprednisolone (IVMP) as measured by magnetization
      transfer imaging. METHODS: Magnetization transfer ratios (MTR) of 225 contrast
      enhancing lesions (CEL), in four RRMS patients were serially determined for 12
      months before and 12-18 months after contrast enhancement in a baseline vs
      treatment trial with IFNbeta-1b. During the baseline period, 185 new CEL were
      identified: 76 were treated with IVMP (1 g/day x 5 days) and designated steroid
      CEL (S-CEL); the remaining 109 were considered baseline lesions (BCEL). During
      IFNbeta-1b treatment, 40 CEL (IFN-CEL) were identified. After image co
      registration, regions of interest (ROIs) defining new CEL were transferred to the
      MTR image set to determine the mean lesion MTR on each monthly exam. The lesion
      MTR was compared to MTR of normal appearing white matter (NAWM) on the same exam.
      RESULTS: As early as 12 months prior to enhancement, the MTR of CEL was reduced
      compared to NAWM (mean 9.43 +/- 3.2%; P<0.001). The further reduction in MTR (28%
      +/- 4.0) at the time of contrast enhancement was not significantly different for
      BCEL, S-CEL or IFN-CEL Following enhancement, lesion recovery for IFN-CEL
      (P=0.02) and S-CEL (P=0.002) was significantly higher than BCEL CONCLUSION:
      IFNbeta-1b and IVMP reduce tissue damage and promote lesion recovery in RRMS
      patients. The additional benefit of IVMP compared to IFNbeta-1b may be related to
      its inhibitory effect on demyelination.

PMID- 11321195
TI  - Disability and prognosis in multiple sclerosis: demographic and clinical
      variables important for the ability to walk and awarding of disability pension.
AB  - OBJECTIVE: To evaluate disability and prognosis in an untreated population-based
      incidence cohort of multiple sclerosis (MS) patients. METHODS: The Expanded
      Disability Status Scale (EDSS) score was recorded in 220 MS patients. Disease
      progression was assessed by life table analysis with different endpoints and
      multivariate Cox regression analysis was performed for evaluation of prognostic
      factors. RESULTS: The probability of being alive after 15 years was 94.8 +/- 1.8%
      (s.e.), of managing without a wheelchair (EDSS < 7.0) 75.8 +/- 3.2%, of walking
      without walking assistance (EDSS<6.0) 60.3 +/- 3.6%, and of not being awarded a
      disability pension 46.0 +/- 3.7%. The probability of still having a relapsing
      remitting (RR) course after 15 years was 62.0 +/- 4.1%. A RR course and long
      interval between the initial (onset) and second episode (> 3 years) predicted
      favorable outcome. There was also a trend towards favorable outcome in patients
      with optic neuritis, sensory symptoms and low age at onset but these factors were
      associated with the RR course. Motor symptoms and high age at onset indicated
      unfavorable outcome, but these factors were associated with the primary
      progressive course. CONCLUSIONS: A RR course and long inter-episode intervals in
      the early phase of the disease were associated with a better outcome. Other onset
      characteristics indicating a favorable outcome were associated with the RR course
      while characteristics indicating an unfavorable outcome were associated with the
      PP course.

PMID- 11321196
TI  - Episodic hyperlibidinism in multiple sclerosis.
AB  - BACKGROUND: Changes in sexual function are commonly associated with MS and occur
      in many forms. Hypersexual thoughts or behavior are rare, but can present on the
      background of persistent cognitive impairment or psychiatric conditions such as
      mania, whereas isolated hypersexuality is still rarer. CASE REPORT: We describe
      the clinical, neuropsychological, electrodiagnostic, neuroimaging and endocrine
      findings in a MS patient with episodes of greatly increased libido. Imaging and
      neuropsychologicol studies indicated frontal lobe dysfunction; hormone studies
      showed no significant changes. CONCLUSION: Episodic hypersexuality can be a
      recurrent transient manifestation of MS.

PMID- 11321197
TI  - Acute pulmonary oedema: presenting symptom of multiple sclerosis.
AB  - Acute pulmonary oedema and headache are both common. The former is usually
      cardiogenic in origin. Severe headache of sudden onset in a young person may be
      suggestive of subarachnoid headache. We describe a 24-year-old man who presented
      with headache and pulmonary oedema, finally ascribed to multiple sclerosis. This
      is the first report of neurogenic pulmonary oedema as the first symptom of
      multiple sclerosis. We review the neuroanatomical basis and experimental evidence
      for neurogenic pulmonary oedema.

PMID- 11321198
TI  - Annotation: conceptions of intelligence.
AB  - This paper argues for the scientific utility of the concept "intelligence". In
      the first section three common arguments against the validity of general
      intelligence are discussed and dismissed. The second section presents the
      evidence in favour of the proposition that individual differences in IQ may be
      based on differences in speed of information processing. However, the third
      section shows that executive functions, particularly inhibitory processes,
      represent a more likely basis for the development of intelligence. The theory of
      the minimal cognitive architecture underlying intelligence and development
      (Anderson, 1992a) shows how speed and executive functioning might represent two
      dimensions to g--one an individual differences (within age) dimension based on
      speed and the other a developmental dimension based on changing executive
      functioning. In the fourth section this theory is used to generate new insights
      on the nature of intellectual disability and specific cognitive deficits and to
      make practical suggestions for educational intervention for low-IQ children.

PMID- 11321199
TI  - Exploring the cognitive phenotype of autism: weak "central coherence" in parents
      and siblings of children with autism: I. Experimental tests.
AB  - Previous twin and family studies have indicated that there are strong genetic
      influences in the etiology of autism, and provide support for the notion of a
      broader phenotype in first-degree relatives. The present study explored this
      phenotype in terms of one current cognitive theory of autism. Parents and
      brothers of boys with autism, boys with dyslexia, and normal boys were given
      tests of "central coherence", on which children with autism perform unusually
      well due to an information-processing bias favouring part/detail processing over
      processing of wholes/meaning. Results indicated that fathers of boys with autism,
      as a group, showed piecemeal processing across four tests of central coherence.
      This was not true for any other group. These findings raise the possibility that
      the broader autism phenotype may include a "cognitive style" (weak central
      coherence) that can confer information-processing advantages.

PMID- 11321200
TI  - Exploring the cognitive phenotype of autism: weak "central coherence" in parents
      and siblings of children with autism: II. Real-life skills and preferences.
AB  - Information on everyday life activities and preferences in both social and
      nonsocial domains was obtained from parents and children who had taken part in an
      experimental study of central coherence. Comparisons were made between parents
      who had a son with autism, parents with a dyslexic son, and families without a
      history of developmental disorder, as well as the male siblings in these
      families. Data on everyday preferences and abilities were elicited by means of an
      experimental questionnaire. Significant group differences in social and nonsocial
      preferences were found, suggesting that some parents showed similarities with
      their son with autism, in preference for nonsocial activities and ability in
      detail-focused processing. A similar experimental questionnaire, completed by
      parents on behalf of their sons, discriminated between autism group probands and
      controls, but did not differentiate sibling groups. The relevance of the
      nonsocial items to central coherence is discussed in the light of the findings in
      Part I: autism parents who reported more autism-related nonsocial (but not
      social) preferences, tended to show a piecemeal processing style on the
      experimental tasks.

PMID- 11321201
TI  - Action-monitoring and intention reporting in children with autism.
AB  - The " mindblindness" theory of core cognitive impairment in autism and at least
      one of the executive theories of the core cognitive deficit both predict that
      children with autism should find it difficult to report what their intention was
      when it diverged from an outcome. The former predicts this because it takes
      intention reporting to require a " theory of mind " and the latter predicts it
      because the theory posits an impairment in the monitoring of goal-directed
      actions. The latter also predicts impairments in the ability to monitor basic
      actions. Our three studies failed to support either of these views. Experiment 1
      demonstrated intact abilities in the monitoring of basic actions (detecting which
      stimulus of a number of stimuli one is controlling). Experiment 2 demonstrated
      intact abilities in reporting an intention, both for self and for another agent,
      when the outcome was unintended but desired. In Experiment 3, using the novel
      "transparent intentions task", we found (with a minor qualification) intact
      ability in reporting on nonballistic intended actions when the result that the
      action achieved was unexpected. The implications of these results for views of
      the relation between theory of mind and executive difficulties in autism are
      discussed.

PMID- 11321202
TI  - Phonological processing, language, and literacy: a comparison of children with
      mild-to-moderate sensorineural hearing loss and those with specific language
      impairment.
AB  - Phonological skills, language ability, and literacy scores were compared for four
      groups: 19 children with mild-to-moderate sensorineural hearing loss (SNH), 20
      children with specific language impairment (SLI), 20 controls matched on
      chronological age to the SNH group (CA), and 15 controls matched on receptive
      vocabulary level to a subset of the SLI group (CB). In common with the SLI group,
      mean scores of children with mild-to-moderate hearing loss were significantly
      poorer on tests of phonological short-term memory, phonological discrimination,
      and phonological awareness than CA controls. No differences between group means
      were observed in SNH and CA control groups on vocabulary, digit and sentence
      recall, sentence comprehension, and literacy scores. However, there was
      considerable individual variation within the SNH group. Nearly 50% of the SNH
      group showed phonological impairment associated with poorer expressive and
      receptive vocabulary and higher hearing thresholds than remaining children
      without phonological impairment. Nonword repetition deficits were observed in SNH
      subgroups with and without phonological impairment and were of a similar
      magnitude to those observed in children with SLI. Indeed, poorer repetition in
      children with SLI could only be differentiated from children with SNH on
      phonologically complex nonwords. Overall, findings suggested major problems in
      nonword repetition and phonological impairment occurred without clinically
      significant deficits in wider language and literacy abilities in children with
      mild-to-moderate sensorineural hearing loss. Implications for theories of SLI are
      discussed.

PMID- 11321203
TI  - DSM-IV related ADHD symptom ratings by professional caretakers in residential
      treatment centres.
AB  - In this study the factorial validity and the reliability of DSM-IV related ADHD
      symptom ratings made by care professionals working in residential treatment
      centres were determined in a sample of 412 residential youngsters. Three
      concurrent models of the ADHD disorder were investigated, a one-factor model
      comprising all 18 symptoms, a two-factor model with the Inattention and
      Hyperactivity/Impulsivity symptoms, respectively, combined and a three-factor
      model comprising Inattention, Hyperactivity, and Impulsivity symptoms,
      respectively. An analysis of the covariance structure shows acceptable fits for
      both the two- and the three-factor models, slightly favouring the three-factor
      model. The internal consistencies, the test-retest reliabilities, and the inter
      rater reliabilities turned out to be good to excellent for all scales based on
      each of the three concurrent models.

PMID- 11321204
TI  - Response execution and inhibition in children with AD/HD and other disruptive
      disorders: the role of behavioural activation.
AB  - This study was aimed at (a) replicating findings of slow and variable response
      execution and slow response inhibition in Attention Deficit/Hyperactivity
      Disorder (AD/HD). (b) investigating whether these deficits are specifically
      related to AD/HD or may also be observed in Oppositional Defiant Disorder (ODD),
      and children comorbid for AD/HD+ODD, and (c) examining the role of activation
      level in task performance of children with AD/HD. To meet these aims, the stop
      paradigm was administered at three levels of activation, using a slow, medium,
      and fast presentation rate of stimuli, to 4 groups of children: 24 AD/HD
      children, 21 children with ODD, 27 children with comorbid AD/HD + ODD, and 41
      normal controls. As hypothesized, children with AD/HD exhibited a slow response
      execution process with considerable variability in the speed of responding
      compared to normal controls. Slow response execution was also observed in the
      comorbid AD/HD+ODD group but not in the pure ODD group. Larger variability in the
      speed of responding was common to all disruptive groups compared with controls.
      In contrast to our hypothesis, no group differences emerged for inhibitory
      functioning. Finally, the slow event rate condition caused a further
      deterioration in the speed of the response execution process in both the AD/HD
      group and ODD group.

PMID- 11321205
TI  - Efficacy of cognitive-behavioral treatment and fire safety education for children
      who set fires: initial and follow-up outcomes.
AB  - The efficacy of cognitive-behavioral treatment (CBT) and fire safety education
      (FSE) for children who had set a recent fire was evaluated. Assessments were
      conducted with 38 children who were randomly assigned to CBT or FSE and with
      another 16 children who received a brief intervention (home visit from a
      firefighter or HVF) that paralleled routine services. Measures in four domains
      related to the child's fire history were obtained from children and their parents
      at pre-treatment, post-assessment, and 1-year follow-up. There were several
      improvements at post-treatment for all conditions on measures of fire
      involvement, interest, and risk. However, CBT and FSE were more efficacious than
      HVF on certain measures, including the frequency of firesetting and proportion of
      children playing with matches, severity of individualized problems with fire, and
      involvement in fire-related acts and other deviant fire activities. These and
      other group differences, along with certain time effects, were evident at 1-year
      follow-up. The findings from this initial comparison study are discussed in the
      context of needed clinical and research directions for work with firesetters and
      their families.

PMID- 11321206
TI  - Two-year prediction of children's firesetting in clinically referred and
      nonreferred samples.
AB  - This study provides the first prospective evaluation of the course and predictors
      of children's involvement with fire over a 2-year period in 268 nonpatient and
      patient children (ages 6-13 yrs). Selected predictor variables obtained at
      initial (intake) assessment, which included fire-specific and general
      psychosocial measures, were examined in each sample using hierarchical logistic
      regression. Both samples reported heightened involvement in matchplay and
      firesetting at follow-up, though the frequency of each behavior was nearly four
      times higher in patients than in nonpatients. Fifty per cent and 59% of the
      initial firesetters in the nonpatient and patient samples, respectively, became
      recidivists. In the nonpatient sample, the child's initial involvement in
      firesetting and level of covert antisocial behavior were the only psychosocial
      predictors of follow-up firesetting that added incremental variance beyond
      demographics. In the patient sample, the child's initial involvement in fire
      related acts and level of covert antisocial behavior were the only predictors of
      follow-up firesetting beyond any initial involvement in matchplay. The findings
      highlight somewhat different risk factors for subsequent firesetting in
      nonpatient and patient children, especially prior firesetting and matchplay,
      respectively, and bear implications for the prevention of firesetting recidivism.

PMID- 11321207
TI  - Parental concordance and comorbidity for psychiatric disorder and associate risks
      for current psychiatric symptoms and disorders in a community sample of juvenile
      twins.
AB  - In this report we characterize associations between parental psychiatric
      disorders and children's psychiatric symptoms and disorders using a population
      based sample of 850 twin families. Juvenile twins are aged 8-17 years and are
      personally interviewed about their current history of DSM-III-R conduct,
      depression, oppositional-defiant, overanxious, and separation anxiety disorders
      using the CAPA-C. Mothers and fathers of twins are personally interviewed about
      their lifetime history of DSM-III-R alcoholism, antisocial personality disorder,
      generalized anxiety disorder, major depression, panic disorder/agoraphobia,
      social phobia, and simple phobia using a modified version of the SCID and the
      DIS. Generalized least squares and logistic regression are used to identify the
      juvenile symptoms and disorders that are significantly associated with parental
      psychiatric histories. The specificity of these associations is subsequently
      explored in a subset of families with maternal plus parental psychiatric
      histories with a prevalence > 1%. Parental depression that is not comorbid or
      associated with a different spousal disorder is associated with a significantly
      elevated level of depression and overanxious disorder symptoms and a
      significantly increased risk for overanxious disorder. Risks are higher for both
      symptomatic domains in association with maternal than paternal depression, and
      highest in association with maternal plus paternal depression. Risks for
      otherjuvenile symptoms and disorders index the comorbid and spousal histories
      with which parental depression is commonly associated. Paternal alcoholism that
      is not comorbid or associated with a maternal disorder is not significantly
      associated with current psychiatric symptoms or disorders in offspring. Risks for
      oppositional-defiant or conduct symptoms/disorders in the offspring of alcoholic
      parents index parental comorbidity and/or other spousal histories.

PMID- 11321209
TI  - Stress, emotional skill, and illness in children: the importance of
      distinguishing between children's and parents' reports of illness.
AB  - This study examined relationships of stress (negative event frequency during the
      last year) to reports of illness among 92 children, aged 10 to 13 years.
      Children's health status was reported separately by children and parents, and
      children's skill in identifying and communicating their feelings was tested for
      direct and buffering relationships on illness reports. Analyses controlled for
      demographics and negative affect of both children and parents, and children's
      verbal ability was also tested for confounding. Results showed that stress
      correlated positively with children's poor health, whether the children's health
      status was reported by children or by parents. Children's emotional skill was
      correlated with better health when health was reported by children, but with
      worse health when health was reported by parents. Further, moderator analyses
      indicated that the relationship between negative event frequency and children's
      poor health as reported by parents held only for children with high levels of
      skill in identifying and communicating feelings. These findings suggest that
      negative life events impair children's health, but that the health reports of
      children and parents are quite different, and parents' views may be affected by
      children's skill in communicating their internal states.

PMID- 11321208
TI  - War exposure and maternal reactions in the psychological adjustment of children
      from Bosnia-Hercegovina.
AB  - As part of a UNICEF-sponsored Psychosocial Programme in Bosnia, data were
      collected from a representative sample of 339 children aged 9-14 years, their
      mothers, and their teachers in order to investigate risk and moderating factors
      in children's psychological reactions to war. Self-report data from children
      revealed high levels of post-traumatic stress symptoms and grief reactions, but
      normal levels of depression and anxiety. Mothers' self-reports also indicated
      high levels of post-traumatic stress reactions, but normal levels of depression
      and anxiety. Child distress was related to both their level of exposure and to
      maternal reactions. Structural equation modeling was used to quantify the
      relationships between these risk factors and child distress, and to examine
      putative pathways to account for the association between child and maternal
      health. Children's adjustment was associated significantly with both exposure
      (phi = .37) and maternal mental health (phi = .37). Modeling also revealed a
      significant distorting effect of mother's own mental health on behavioural
      ratings of her child (psi = .59). Although evidence exists for an association
      between maternal mental health and mother rating errors, there is also a
      substantive association between maternal mental health and children's adjustment
      following war.

PMID- 11321210
TI  - The assessment of the situational specificity of children's problems behaviour in
      peer-peer context.
AB  - In both theory and research the general issue of the extent to which children's
      problem behaviour is generalised across situations, and to what extent it is
      situation specific, has been neglected. In the clinical assessment of disordered
      children, too, little attention has been paid to the specific situations in which
      these children display their inappropriate behaviour. In this study the Taxonomy
      of Problematic Social Situations (TOPS) (Dodge, McClaskey, & Feldman, 1985) was
      employed. This is a questionnaire in which the child's teacher is asked to rate
      the likelihood of a child responding in an inappropriate manner in a specific
      situation. Characteristics of TOPS were investigated both in randomly selected
      normal school children and in boys with a conduct disorder. Four factors appeared
      to underlie the TOPS scores from 652 randomly selected boys and girls from grades
      1 to 6, these being: teachers' scores for the types of problem situation Being
      Disadvantaged, Coping with Competition, Social Expectations of Peers, and Teacher
      Expectations. Because of the high internal consistency of the four factors, TOPS
      was abbreviated to a TOPS-Short Form (18 instead of 44 items). The four-factor
      model was cross-validated by means of a second sample of 326 boys and girls. A
      model with only one general problem behaviour factor did not fit the data of both
      samples. When the four specific factors were added a satisfactory fit resulted.
      Moreover, it was found that in the first sample 52% of the variance was explained
      by the general factor, whereas 18% of the variance was explained by the four
      specific factors together. Thus, the extent to which problem behaviour is
      situation specific should not be disregarded. In all four types of problem
      situation, boys showed more inappropriate behaviour than girls. With increasing
      age, children were rated as being more competent in dealing with the problem
      situation Being Disadvantaged. Teachers rated the four types of problem situation
      as more problematic for boys with a conduct disorder (N = 42) than for normal
      control boys (N = 67). Conduct disordered boys also differed individually in the
      number of situational types that were problematic for them. With respect to
      clinical implications, the identification of the particular social context in
      which a conduct disordered child displays his or her inappropriate behaviour may
      help refine treatment goals: more adequate social functioning should be aimed at
      specifically in those situations that are problematic.

PMID- 11321211
TI  - Client and consumer interests: a driving force for change.

PMID- 11321212
TI  - Evaluation of bacteria isolated from infected eyes of captive, non-domestic
      animals.
AB  - Bacteria isolated from the eyes of captive species with suspected ocular
      infections at London Zoo were identified by standard methods. The sensitivity of
      the organisms to several topical antibiotics was determined by using sensitivity
      discs, and the minimum inhibitory concentrations of chloramphenicol and fusidic
      acid were determined. Correlations were evaluated between the results from the
      antibiotic discs and the minimum inhibitory concentrations and, where possible,
      between the clinical response to treatment and the results of bacteriological
      sensitivity tests. Unlike the isolates found in cats and dogs gram-positive cocci
      accounted for 54 per cent of isolates but almost half of the bacteria isolated
      were gram-negative organisms.

PMID- 11321213
TI  - Gender, age, breed and distribution of morbidity and mortality in insured dogs in
      Sweden during 1995 and 1996.
AB  - More than 200,000 dogs insured by one Swedish company at the beginning of either
      1995 or 1996 were included in a retrospective, cross-sectional study. They could
      be covered for veterinary care at any age, but were eligible for life insurance
      only up to 10 years of age. Accessions for veterinary care that exceeded the
      deductible cost were used to calculate the risk of morbidity. The morbidity and
      mortality data have been stratified by gender, age, breed, location and human
      population density. In each year, 13 per cent of the dogs experienced at least
      one veterinary care event and the mortality risk was 3.0 per cent. The risk of
      morbidity varied with age, gender, breed, and location. The risk of mortality
      increased principally with age. It was possible to derive population-based risks
      of morbidity and mortality from these insurance data.

PMID- 11321214
TI  - Ultrasound-guided percutaneous lung biopsy in sheep.
AB  - Lung biopsies were taken through the ninth intercostal space on the two sides of
      the thorax of 10 clinically healthy sheep, using a Tru-Cut needle on one side and
      the Bard Biopty-System on the other. Nine of the 10 sheep remained clinically
      healthy, but one coughed transiently and had a mild bloody discharge from the
      right nostril immediately after the biopsy. The sheep were slaughtered 10 days
      later and the lungs and pleura were examined macroscopically; there were either
      no lesions or only small scars visible at the sites of the biopsies. However,
      well-developed subpleural nodules due to parasites were observed in some of the
      lungs. There were no adhesions between the costal and pulmonary pleurae. Of the
      20 biopsy specimens, 18 were ideal for histological examination, and none of them
      was histologically normal. Mild interstitial pneumonia was diagnosed in 15
      specimens, chronic bronchiolitis in nine specimens, and hyperplasia of smooth
      muscle or connective tissue in 17.

PMID- 11321215
TI  - Differences between primary and secondary infestations with the sheep scab mite,
      Psoroptes ovis.

PMID- 11321216
TI  - Colonisation state and colostral immunity to Mycoplasma hyopneumoniae of
      different parity sows.

PMID- 11321217
TI  - Male pseudo-hermaphroditism in a dog: a clinical case.

PMID- 11321218
TI  - Severe urolithiasis due to trimagnesium orthophosphate calculi in a goat.

PMID- 11321219
TI  - Inclusion of dimetridazole in gamebird feeds.

PMID- 11321220
TI  - Corporate practice.

PMID- 11321221
TI  - Unseasonal snake bites in dogs.

PMID- 11321222
TI  - Retired members of the RCVS.

PMID- 11321223
TI  - Sociology and the public understanding of science: from rationalization to
      rhetoric.
AB  - This paper contributes to the reappraisal of sociological theories of modernity
      inspired by the sociology of scientific knowledge (SSK). As much as these
      theories rely on received ideas about the nature of science that SSK has called
      into doubt, so do they rely on ideas about the public understanding of science.
      Public understanding of science has been assumed to conform to the monolithic
      logic and perception of science associated with rationalization, leading to an
      impoverished view of the cognitive outlook of the modern individual.
      Rationalization has become the basis for the construction of theoretical critique
      of science divorced from any clear reference to public understanding, with the
      result that theory has encountered considerable problems in accounting for public
      scepticism towards science. However, rather than question rationalization, the
      more typical strategy has been to propose radical changes in the modernization
      process, such as postmodernism and the risk society. Against this, an alternative
      view of public understanding is advanced drawn from SSK and rhetorical
      psychology. The existence of the sociological critique of science, and SSK in
      particular, suggests that the meaning of science in modernity is not monolithic
      but multiple, arising out of a central dilemma over the universal form of
      knowledge-claims and their necessarily particular, human and social grounding.
      This dilemma plays out not only in intellectual discourses about science, but
      also in the public's understanding of science. This argument is used to call for
      further sociological research into public understanding and to encourage
      sociologists to recognize the central importance of the topic to a proper
      understanding of modernity.

PMID- 11321224
TI  - Zygmunt Bauman's poisoned gift of morality.
AB  - Bauman's attempt to develop a sociological theory of morality turning around
      fundamental premises of Durkheim's approach fails in the last analysis, since in
      Bauman's view the 'moral party of two' does not constitute a social situation. It
      is argued that the necessary condition to think sociologically about morality is
      the concept of reciprocity and thus one can arrive at a view of morality in
      postmodernity consistent with Bauman's earlier theory of practice. If Bauman's
      idea about responsibilty as the core of morality is transformed to the idea of an
      appeal of history to compassion and is supplemented with the idea of reciprocity
      as an emerging norm it is possible to outline a sociological theory of moral
      practice according to postmodern conditions.

PMID- 11321225
TI  - Witchcraft, genealogy, Foucault.
AB  - This paper is a genealogical reflection on both the historiography of European
      witchcraft and the dynamics of witchcraft trials. I argue that traditional
      scholarly assumptions about the 'unsophisticated' nature of early modern European
      mentalities result in inadequate representations of accused witches and of the
      social contexts and processes of the trials. Genealogy, by contrast,
      problematizes fundamental notions such as reason, order, power and progress in
      ways that not only provide a different range of effective tools for the analysis
      of belief in witchcraft, but also underline its crucial significance for social
      theory. In the final section, an analysis of a typical trial is undertaken
      employing key genealogical insights into confession, torture, truth,
      governmentality, power, pleasure and pain.

PMID- 11321226
TI  - Religion and attitudes towards nature in Britain.
AB  - Religious institutions have been identified as important conduits in shaping
      social attitudes toward nature and the environment. Using Lynn White's historical
      thesis that Judeo-Christianity has cherished the domination of nature ('dominion'
      belief) by humans as our frame of reference, this article examines the impact of
      religion, specifically Abrahamic and Judeo-Christian beliefs, on environmental
      attitudes in Britain. Based on the 1993 British Social Attitudes Survey, a
      nationally representative sample of the adult population in Britain, the
      multivariate results of this paper suggest that: (a) there is no significant
      difference between Christians and non-Christians concerning environmental
      attitudes; (b) Roman Catholics are the most sceptic toward nature among Christian
      denominations; and (c) irrespective of religious identification, the two most
      notable and consistent factors in determining pro-dominion attitudes in Britain
      are educational attainment and particularly levels of scientific knowledge about
      the natural environment.

PMID- 11321227
TI  - Uncertain identities and health-risking behaviour: the case of young people and
      smoking in late modernity.
AB  - This paper argues that 'uncertain identities' are a distinct contributing factor
      to the residual and intractable level of smoking among young people. Further, it
      argues that the significance of this factor is increased by the specific
      social/historical context of late modernity. Findings from research with 15 to 16
      year olds in the East Midlands of England are used to explore the role that
      smoking is perceived to play in constructing a self identity. A voluntaristic
      perspective is adopted on the use of tobacco, reflecting both the focus on young
      people's motivation to smoke and the tendency for many young people to perceive
      smoking as a matter of personal choice. Smoking was found to have a symbolic
      significance not only in terms of the presentation of self to others but also in
      terms of the reflexive construction of the self by those involved. The paper
      analyses the role of smoking in relation to self-image, self-empowerment and self
      affirmation and it is concluded that for many young people smoking has certain
      benefits in terms of coping with uncertain identities.

PMID- 11321228
TI  - Science against modernism: the relevance of the social theory of Michael Polanyi.
AB  - Science, as an institution, is widely taken by sociologists to exemplify the
      modern tendency towards vesting trust and authority in impersonal offices and
      procedures, rather than in embodied human individuals. Such views of science face
      an important challenge in the social philosophy of Michael Polanyi. His work
      provides important insights into the continuing role of embodied personal
      authority and tradition in science and, hence, in late modernity. I explicate
      Polanyi's relevance for social theory, through a comparison with Weber's essay
      'Science as a Vocation'. An understanding of the personal dimensions of trust and
      authority in science suggests practical limits to the position of Giddens on the
      disembedding of social relations and on the scepticism and reflexivity of
      modernity.

PMID- 11321229
TI  - Colonizing nature: scientific knowledge, colonial power and the incorporation of
      India into the modern world-system.
AB  - In this paper, the role of scientific knowledge, institutions and colonialism in
      mutually co-producing each other is analysed. Under the overarching rubric of
      colonial structures and imperatives, amateur scientists sought to deploy
      scientific expertise to expand the empire while at the same time seeking to take
      advantage of the opportunities to develop their careers as 'scientists'. The role
      of a complex interplay of structure and agency in the development of modern
      science, not just in India but in Britain too is analysed. The role of science
      and technology in the incorporation of South Asian into the modern world system,
      as well as the consequences of the emergent structures in understanding the
      trajectory of modern science in post-colonial India is examined. Overall,
      colonial rule did not simply diffuse modern science from the core to the
      periphery. Rather the colonial encounter led to the development of new forms of
      scientific knowledge and institutions both in the periphery and the core.

PMID- 11321230
TI  - The myth of the best argument: power, deliberation and reason.
AB  - Power in communication takes two main forms. As 'external' power, it consists in
      the ability to acknowledge or disregard a speaker or a discourse. As 'internal'
      power, it is the ability of an argument to eliminate other arguments by
      demonstrating its superiority. A positive or negative value may be ascribed to
      these forms of power. Four ideal-typical positions are discussed--strategy,
      technocracy, constructionism, and deliberation. Public deliberation has three
      virtues--civic virtue, governance virtue and cognitive virtue. Deliberation
      lowers the propensity to, and the benefit of, strategic behaviour. It also
      increases knowledge, enhancing the quality of decisions. For Habermas, the unity
      of reason is expressed in the possibility of agreement on the most convincing
      argument. However, sometimes conflicts are deep-lying, principles and factual
      descriptions are profoundly different, and uncertainty is radical. The best
      argument cannot be found. There is no universal reason. The question is whether
      non-strategic agreement may spring from the incommensurability of languages. In
      search of an answer, Rawls's concept of overlapping consensus, the feminist
      theory of the public sphere, and the idea of deliberation as co-operation are
      discussed. The argument developed is that the approach to deliberative democracy
      may be renewed by rethinking its motivational and cognitive elements. Public
      deliberation is grounded on a pre-political level of co-operation. Intractable
      controversies may be faced at the level of practices, looking for local,
      contextual answers.

PMID- 11321231
TI  - Dialectical dialogue: the struggle for speech, repressive silence, and the shift
      to multiplicity.
AB  - In the present essay I intend to explore 'dialectical dialogue' in three distinct
      moments: the battle for recognition, the ethics of giving recognition, and the
      multiplicity of conversation. The essay begins with Hegel's figures of Master and
      Slave portraying the struggle of speech for recognition. This struggle culminates
      in a duel for mastery, which implies the repression and silencing of the other's
      speech. Ethical dialogue comes as a response to repressive silence, calling the
      other into egalitarian exchange. Ethical dialogue as such, however, remains
      within the dialectical framework of agonistic relations. To shift from dialectics
      to multiplicity, the essay turns from the politics of recognition to the poetics
      of conversation, to polyphony and to passage. I will follow the three moments
      both separately, through particular dialogic instances and theoretical
      perspectives, and as they develop, respond to, and shift from one to the other.
      Together they will portray an idea of the 'social' as a critical dialogic stance
      with its inherent dialectical betweenness and potential opening and expanding
      multiplicity.

PMID- 11321233
TI  - The role of Fas-FasL in CD8+ T-cell-mediated insulin-dependent diabetes mellitus
      (IDDM).
AB  - In the past few years a number of studies have evaluated the contributions of
      different cytolytic pathways in the autoimmune destruction of pancreatic beta
      cells, which results in insulin-dependent (type I) diabetes mellitus. Conflicting
      results continue to emerge regarding the role of Fas-mediated apoptosis in beta
      cell destruction. This is likely to reflect differences inherent to the model
      systems under investigation, as well as the pleiotropic nature of the genes that
      are involved in cytotoxicity. Despite these complications, it may be possible to
      reconcile some of these apparently conflicting results by considering that T-cell
      mediated cytotoxicity can occur simultaneously by several mechanisms and that
      variables such as the cytokine milieu and the strength of the signal to the T
      cell received through the T-cell receptor complex may alter the relative
      contribution of each cytolytic pathway to beta-cell destruction.

PMID- 11321232
TI  - The Fas signaling connection between autoimmunity and embryonic lethality.
AB  - The first gene to cause systemic autoimmune disease in mice was identified as the
      fas gene, which is mutated in lymphoproliferative (lpr) mice. These mice
      exhibited a defect in activation-inducted cell death of T cells and B cells in
      vivo, causing a failure of proper clearance of immune cells and defective down
      modulation of an immune response. This led to the speculation that apoptosis
      defects may play a role in defective down-modulation of the hyperimmune response
      observed in human autoimmune diseases. More recently, scientists have generated
      different mouse lines with defects in Fas-apoptosis-associated molecules such as
      FADD and Apaf-1. These mice, however, died during embryonic development and did
      not develop autoimmune disease. These findings suggest that molecules associated
      with Fas apoptosis signaling can be important at the most limited levels for
      development of the immune system but also have more global apoptosis roles in
      other systems. We propose that the more global role of Fas-associated apoptosis
      molecules should be considered when evaluating their role in autoimmune disease.

PMID- 11321234
TI  - Fas-FasL in Hashimoto's thyroiditis.
AB  - Hashimoto's thyroiditis is a common chronic autoimmune disease characterized by
      the loss of thyroid follicular cells (thyrocytes) that are gradually replaced by
      lymphocytic infiltration and diffuse fibrosis. These morphological findings
      suggested that autoreactive T-cell clones were responsible for thyrocyte
      destruction and hypothyroidism through effector-target cytotoxic recognition.
      Later, autonomous interaction between thyrocyte Fas and FasL has been proposed as
      a major mechanism of thyrocyte depletion in Hashimoto's thyroiditis. Here, we
      analyze the possible role of Fas and FasL in the pathogenesis of Hashimoto's
      thyroiditis. We suggest that the Fas-FasL system dictates the outcome of the
      autoimmune response by acting on both immune and target cells.

PMID- 11321235
TI  - Fas (CD95, Apo-1) ligand gene transfer.
AB  - Gene therapy represents a new form of medical intervention that relies on direct
      transfer of genetic materials into patients. Although initially envisioned as a
      treatment for genetic diseases, gene therapy is currently being explored for a
      wide range of acquired disorders including cancer, cardiovascular diseases,
      arthritis, and neurodegenerative disorders. Since most acquired diseases are not
      caused by single gene mutations, the choice of therapeutic genes is crucial for
      the success of the gene therapy. In this review, we discuss the progresses that
      have been made and problems that remain to be resolved in using Fas (CD95, Apo-1)
      ligand gene for the treatment of acquired disorders. Fas ligand is a member of
      the tumor necrosis factor family that can induce both apoptosis and activation of
      various cells. While Fas ligand gene transfer indeed eliminates cancer cells and
      inflammatory cells through apoptosis, it also kills normal cells and initiates
      inflammation in certain tissues. Thus, new strategies that can modify the
      apoptotic or proinflammatory activities of the FasL will help to fully realize
      the potential of the FasL gene therapy.

PMID- 11321236
TI  - Hepatitis B immunization of healthy elderly adults: relationship between naive
      CD4+ T cells and primary immune response and evaluation of GM-CSF as an adjuvant.
AB  - The efficacy of granulocyte-macrophage colony-stimulating factor (GM-CSF) to
      enhance the primary immune response to hepatitis B vaccine was studied in healthy
      elderly with young volunteers included as controls in this double-blind, placebo
      controlled trial of GM-CSF as an immune adjuvant. Naive T-helper cells
      (CD4+CD45RA+) were determined at baseline. Forty-five healthy elderly (average
      age, 74 years) and 37 healthy young controls (average age, 28 years) were
      randomized. Hepatitis B vaccine was administered at 0, 1, and 6 months. GM-CSF as
      a single injection of either 80 microg or 250 microg with the first and second
      doses of hepatitis B vaccine. In this trial GM-CSF did not enhance antibody
      responses. However, the antibody responses were dramatically different between
      these two groups: 35/35 young developed a protective titer versus 19/45 elderly
      (P < 0.0001). In addition, the mean logarithm of anti-hepatitis B antibody level
      in the 35 young who completed the study was 3.17 (log mIU/ml) but only 2.21 in
      the 19 elderly responders (P < 0.0001). Naive T-helper cells differed
      significantly between the two groups: the mean percentage of CD4+CD45RA+ T cells
      was 47.9% versus 35.0% (P < 0.0001) in the young and elderly volunteers
      respectively. Naive T cells also differed significantly between elderly who did
      or did not respond to HBV (39.9% vs. 31.7%, P = 0.039). Using linear regression,
      age, and percent naive, CD4 T cells were determined to significantly influence
      the anti-hepatitis B antibody response, but sex and dose of GM-CSF did not. For a
      two-parameter model: logarithm of antibody titer = (-0.038 x age in years) +
      (0.031 x % naive CD4T cells) + 2.68; adjusted r2 = 0.605 and P < 0.0001. However,
      age had a larger effect than naive CD4 T cells, i.e., in comparing young and
      elderly groups the log antibody titer decreased by 1.73 due to the increase in
      age but only 0.40 due to the decrease in naive CD4 T cells. Thus, there was a
      large effect of age that could not be explained by the quantitative change in the
      naive T-helper cells.

PMID- 11321237
TI  - Lymphocyte subset populations in children with polysaccharide antibody deficiency
      following cardiac transplantation.
AB  - Pneumococcal polysaccharide (PPS) antibody deficiency occurs in some children
      immunosuppressed following cardiac transplantation in early childhood. We studied
      lymphocyte subset populations in these children to identify patterns associated
      with antibody deficiency, particularly in CD21 + B cells. Lymphocyte surface
      markers CD3, CD4, CD8, CD19, and CD21 were measured on whole blood by FACS
      analysis in four patient groups: cardiac transplant patients who did and did not
      respond to PPS, nontransplanted cardiac patients, and normal controls. Absolute
      cell numbers were compared with age-related normal ranges. The proportion of
      children with values below the age-related 25th percentile in each group was
      compared. Normal controls had significantly more CD3+, CD8+, and CD19+ cells,
      even when age-related differences were accounted for. Control groups had
      significantly more CD19 cells than transplant patients and transplanted PPS
      responders and cardiac controls had more mature B cells (CD21+) than transplanted
      PPS nonresponders. PPS antibody deficiency following pediatric cardiac
      transplantation may be related to an immaturity in B cells due to
      immunosuppression commenced in early childhood.

PMID- 11321238
TI  - Characterization of the impaired antipneumococcal polysacharide antibody
      production in immunosuppressed pediatric patients following cardiac
      transplantation.
AB  - We previously have demonstrated impaired pneumococcal polysaccharide IgG antibody
      responses in children immunosuppressed following cardiac transplantation in early
      childhood. We have further characterized the antibody defect. To further
      investigate the production of antibody, antipneumococcal polysaccharide (PPS)
      specific IgM, IgG, IgG subclasses, and IgA were measured in postvaccination sera
      by enzyme-linked immunosorbent assay. Two groups were studied: posttransplant
      children who made pneumococcal antibody in vivo following natural exposure or PPS
      immunization (R) and those with an impaired response (NR). There was no
      difference in IgM or IgA levels between R and NR. IgG and IgG2 levels were higher
      in R than NR (P = 0.002), even after adsorption of nonspecific common cell wall
      antigen antibody. Differences in anti-pneumococcal antibody levels suggest that
      immunoglobulin isotype switching from IgM to IgG and particularly IgG2 is
      impaired in patients immunosuppressed at a young age. These findings confirm data
      regarding the effect of immunosuppressive agents derived from animal models in
      humans.

PMID- 11321240
TI  - Changes in the pathogenesis and prevention of chronic lung disease of
      prematurity.
AB  - With the increasing survival of extremely premature infants there is a large
      number of them who are developing chronic lung disease (CLD), but the severity of
      the lung damage is considerably less than that observed in the classic form of
      bronchopulmonary dysplasia (BPD). Because many of these infants have only a mild
      initial respiratory distress and therefore do not receive aggressive ventilation,
      it is clear that factors other than oxygen toxicity and barotrauma are involved
      in the pathogenesis of this new milder type of CLD. CLD results from the
      interaction of multiple factors that can injure the immature lung. For this
      reason the prevention must be based on the elimination of all the factors
      implicated in its pathogenesis. Clinical and epidemiological data strongly
      suggest that infections, either prenatal or nosocomial, and the presence of a
      patent ductus arteriosus (PDA) play a major role in the development of CLD in
      these infants. For this reason, efforts to prevent CLD in extremely low birth
      weight infants should include an aggressive approach to the prevention and
      treatment of prenatal and neonatal infections and an early closure of the PDA.

PMID- 11321239
TI  - BCG infection in allergen-presensitized rats suppresses Th2 immune response and
      prevents the development of allergic asthmatic reaction.
AB  - Recent investigations demonstrate that bacille Calmette-Guerin (BCG), a potent
      inducer of Th1 response, infection prior to allergen sensitization inhibits Th2
      immune responses to the allergen. However, it is not clear whether BCG infection
      in allergen-presensitized rats switches off Th2 response and prevents allergic
      asthmatic reaction to the subsequent allergen exposure. In this study we
      investigate whether BCG infection in ovalbumin (OVA)-presensitized Sprague-Dawley
      rats suppresses airway hyperresponsiveness and eosinophilic inflammation induced
      by OVA and Th2 cytokine production. BCG infection in OVA-presensitized rats
      significantly inhibited not only the sensitivity of airway smooth muscle to
      electrical field stimulation and acetylcholine but also absolute eosinophil
      counts in bronchoalveolar lavage fluid. As a correlate, interleukin-4 (IL-4)
      production significantly decreased and interferon-gamma (IFN-gamma) slightly
      increased, resulting in a markedly decreased ratio of IL-4-IFN-gamma in OVA
      presensitized rats with BCG infection. These results indicate that BCG infection
      in pre-sensitized rats suppresses allergic asthmatic reaction and Th2 immune
      response. It is possible from these findings that BCG vaccine may be used as an
      immunomodulating agent for the sensitized host with preestablished Th2 memory.

PMID- 11321241
TI  - Aneurysm of the ductus arteriosus in a neonate with 13q-deletion.
AB  - Aneurysm of the ductus arteriosus is a rare abnormality for which different ways
      of pathogenesis are described. We report the case of a fatal thrombosis of an
      aneurysm of the ductus arteriosus in an infant presenting feeding difficulties
      and a mild dysmorphic facies. Karyotype analysis revealed a de novo chromosomal
      deletion 46,XY, del (13)(q12.3,q22.3). To the best of our knowledge, this is the
      first case of an aneurysm of the ductus arteriosus associated with a chromosomal
      aberration.

PMID- 11321242
TI  - Prenatal sonographic diagnosis of bladder outlet obstruction caused by a
      ureterocele associated with hydrocolpos and imperforate hymen.
AB  - We report a case of prenatal bladder obstruction due to a single system
      ureterocele associated with hydrocolpos. Ultrasound at 22 weeks demonstrated an
      enlarged bladder. Serial scans showed progressive ipsilateral obstructive
      uropathy, contralateral hydronephrosis, and oligohydramnios. Neonatal endoscopic
      decompression and hymenotomy was performed with residual decreased ipsilateral
      renal function and dilation. Prenatal bladder obstruction may cause permanent
      renal damage.

PMID- 11321243
TI  - Adverse perinatal outcome of twin pregnancies according to chorionicity: review
      of the literature.
AB  - Twin gestations are at significant increased risk for adverse perinatal outcome.
      As a result, although prospective randomized data is lacking, increased fetal
      surveillance has been advocated for twins. Growth concordance is considered a
      reassuring sign in twins and conversely, discordancy to possibly reflect a
      hostile intrauterine environment at least to the smaller twin. Consequently,
      increased surveillance of discordant twins is commonly practiced. Monochorionic
      twins are at further risk for type-specific perinatal complications, for example,
      twin-twin transfusion syndrome. Recently, precise first-trimester depiction of
      chorionicity has enabled early antepartum stratification of twin gestations
      according to chorionicity, in comparison with previous later (mid- and third
      trimester) ultrasonographic diagnosis of chorionicity. This immediately leads to
      the question whether antenatal testing of twins should differ according to
      chorionicity? Review of the literature supports that despite the existence of
      complications unique to monochorionic twin gestations, dichorionic twins sustain
      an increased risk of adverse perinatal outcome (such as fetal growth restriction)
      in comparison with singletons, and that close antenatal fetal surveillance of
      twins should be performed, irrespective of chorionicity.

PMID- 11321244
TI  - Restrictive dermopathy: case report, subject review with Kaplan-Meier analysis,
      and differential diagnosis of the lethal congenital contractural syndromes.
AB  - We report on a 34-week-old infant with restrictive dermopathy (RD), a rare lethal
      genodermatosis, characterized by an abnormal skin growth and differentiation with
      thin, tightly adherent skin that causes a dysmorphic face, generalized flexion
      joint contractures, and respiratory insufficiency. Kaplan-Meier analysis of 32
      previously well-described infants affected with RD showed a median survival of
      132 hours. Lethal congenital contractural syndromes, including Pena-Shokeir
      phenotype, cerebro-oculo facio-skeletal syndrome, and lethal multiple pterygium
      syndrome, should be considered first in the differential diagnosis. Other lethal
      contractural syndromes are discussed.

PMID- 11321245
TI  - Pilot study of expedited HIV-1 testing of women in labor at an inner-city
      hospital in New York City.
AB  - To evaluate the feasibility of offering voluntary counseling and expedited human
      immunodeficiency virus (HIV) testing to women in labor, and to assess the
      characteristics of two rapid HIV assays compared with results from an expedited
      standard enzyme immunoassay (EIA), with Western blot confirmation, as indicated,
      we undertook a pilot study immediately prior to enactment of New York State
      regulations (August 1999) requiring expedited testing of laboring women (or
      newborns) with undocumented HIV status. From June 9, 1999 through July 2, 1999,
      we offered HIV counseling and testing (C&T) to all medically stable women in
      active labor, 106 of 125 (85%) of whom accepted. One woman was confirmed HIV-1
      seropositive. Rapid assay sensitivity and specificity were: SUDS 100 and 98%, and
      Multispot 100 and 100%, respectively in comparison with 100 and 99% for the
      standard EIA. The positive predictive values (PPV) were SUDS 33%; Multispot 100%;
      and EIA 50%. While our sample size was small, it appears that the accuracy of
      rapid and expedited HIV assays may be improved by requiring two different
      reactive assays before informing women of HIV-seropositive results or initiating
      antiretroviral treatment.

PMID- 11321246
TI  - Prostate-specific antigen: current status.
AB  - PSA is the most important of all tumor markers because it has significant
      applications in all aspects of the management of men with prostatic disease.
      Certainly, the most important utilization of PSA is for early detection of this
      most ubiquitous of all human neoplasms. In this article the authors describe the
      molecular forms of PSA and their characteristics, the factors influencing values
      of serum concentration of PSA, the problems of screening, and particularly the
      possibility to use PSA for detection of prostate carcinoma. A big problem in
      prostate carcinoma detection is the low specificity of PSA at the concentrations
      between 4-10 ng/ml, the so-called diagnostic gray zone, where the incidence of
      prostate carcinoma is only 25%. The authors evaluate the methods which make it
      possible to increase the sensitivity and/or specificity of PSA detection, such as
      PSA density, PSA density of the transition zone, PSA velocity, PSA doubling time,
      age-specific PSA, free PSA and, prospectively, the use of the RT-PCR technique.

PMID- 11321247
TI  - The alkaline single-cell gel electrophoresis/comet assay: a way to study DNA
      repair in radicle cells of germinating Vicia faba.
AB  - Dry seeds are known to accumulate DNA damage with time of storage. Repair of DNA
      lesions during germination of Vicia faba seeds was followed in the radicles using
      the alkaline single-cell gel electrophoresis/comet assay. In this assay nuclei
      were liberated, mixed with agarose and spread out over a microscope slide. After
      lysis of the nuclear membrane and unwinding of the DNA duplex, DNA was stretched
      during electrophoresis, giving a comet-like migration pattern. The more DNA was
      damaged, the higher its mobility. DNA repair took place rapidly the first hours
      of imbibition and more slowly until ca 33 h after onset of germination. A small
      amount of heavily damaged cells remained present. Labelling with BrdU provided
      the possibility to localize repair patches and replicated sites in the comet
      migration pattern. At 15 h of germination, incorporation of BrdU in radicle DNA
      was situated at random over the entire comet. At 33 h, DNA repair was more or
      less accomplished and BrdU was mainly localized in the 'heads' of most comets.

PMID- 11321248
TI  - Production of TGF-beta1 in lungs after low-dose whole-body radiation exposure in
      fibrosing (C57BL/6) and non-fibrosing (C3H/J) mouse strain.
AB  - The aim of the presented study was to observe acute and subacute discrete TGF
      beta1 production after a low-dose whole-body radiation stimulus, known to induce
      thrombocytopenia. TGF-beta1 mRNA production and the number of thrombocytes was
      followed up in two mouse strains with different tendencies to the origination of
      fibroses. Mice of the C57BL/6 and C3H/J strains were exposed to a whole-body dose
      of 7 Gy. Non-irradiated mice of both strains were used as negative controls. The
      relative number of thrombocytes recorded in lung capillaries was significantly
      lower in both strains on day 9 after irradiation in comparison with controls.
      This finding was in accordance with a decrease in the number of thrombocytes in
      the peripheral blood in irradiated animals of both strains. On day 56 relative
      platelet counts reached physiological numbers in comparison to controls. On the
      other hand, TGF-beta1 mRNA production was higher in the C57BL/6 strain (on day 9)
      contrary to minimal production in the C3H/J strain (on day 9) or no production in
      both groups on day 56 and in controls. Thus, TGF-beta1 production without
      increased thrombocyte trapping in lung vessels in acute stage suggests that an
      additional mechanism is involved in low-dose radiation-induced cytokine synthesis
      in lung tissue besides the release of growth factors from thrombocytes.

PMID- 11321249
TI  - HLA alleles and susceptibility to dermatological disorders associated with
      Helicobacter pylori infection: a significant association to HLA-Cw*06.
AB  - The occurrence rate of HLA class I and class II alleles was established in 24
      patients suffering from dermatological disorders associated with the Helicobacter
      pylori infection. The increased frequency of HLA-C*0602, 4 was found to be 0.1875
      compared to 0.0733 in the control group (odds ratio: 2.913; two-sided P value: P
      = 0.0251). Our data suggest that the HLA-Cw6 molecule play a role in the
      susceptibility to the Helicobacter pylori infection.

PMID- 11321250
TI  - Immunohistochemical distribution of DSIP immunoreactivity in the human
      hypothalamus during the first postnatal year. A preliminary report.
AB  - The distribution of DSIP-IR cell bodies and fibers was investigated in the normal
      human hypothalamus during the first postnatal year using the indirect
      immunofluorescence technique. The analysis of the immunohistochemical patterns
      obtained in the seven cases analyzed showed regional differences in the
      localization of cell bodies and fibers. Immunoreactive perikarya were relatively
      few, and were mostly scattered throughout the anterior and the mediobasal
      hypothalamus. DSIP-IR fibers and terminal-like structures were observed
      throughout the rostro-caudal extent of the hypothalamic region. In the present
      study, we noticed qualitative changes in the density of DSIP immunoreactivity in
      several hypothalamic structures such as the preoptic area and the median eminence
      with respect to age. These postnatal differences observed for DSIP could be
      related to neuronal maturation processes occurring at this period in the central
      nervous system as well as other physiological processes controlling the evolution
      of DSIP concentrations. These data are compatible with the proposed role of the
      neuropeptide in the regulation of many postnatal physiological functions.

PMID- 11321251
TI  - Comparative study of neutrophil activities in adults and full-term neonates in
      relation to the method of delivery.
AB  - The aim of this study was to compare the markers of neutrophil activity in
      healthy adults with those in healthy neonates in relation to the method of
      delivery. The following parameters were studied: absolute neutrophil count,
      neutrophil adherence to nylon fiber, NBT reduction, and neutrophil phagocytosis
      of latex particles. The study has shown that the method of delivery significantly
      affects the markers of neutrophil activity measured in umbilical cord blood. The
      levels of these markers were higher in neonates born by elective cesarean section
      than in adults, neonates born vaginally or those born by emergency cesarean
      section. This comparative study of defensive functions of neutrophils from adults
      and neonates indicates that the conflicting results of other studies may be
      caused not only by differences in investigative methodology but also by the fact
      that the eligibility criteria used in these studies did not include the method of
      delivery, which can affect the markers of neutrophil activity via triggering a
      stress response.

PMID- 11321252
TI  - Preventive effect of indomethacin and melatonin on 7, 12-dimethybenz/a/anthracene
      induced mammary carcinogenesis in female Sprague-Dawley rats. A preliminary
      report.
AB  - The aim of the experiment was to analyse the oncostatic effect of nonsteroidal
      antiinflammatory drug INDO, hormone MEL and combination of both substances in
      DMBA-induced mammary carcinogenesis in female SD rats. Chemoprevention started 10
      days before the application of the first dose of DMBA to 35-day-old rats. INDO
      was administered in tap water (20 microg/ml of water) for 3 days in a week (days
      2, 4 and 6), MEL solution in the concentration of 20 microg/ml of tap water was
      administered between 3 p.m. and 8 a.m. for 4 days in a week (days 1, 3, 5 and 7);
      during other days the animals drank tap water only. In combined chemoprevention,
      rats were drinking solutions of INDO and MEL according to the above-mentioned
      scheme. DMBA in the dose of 10 mg/rat was administered intragastrically using a
      probe to all rats 3 times on postnatal days 45, 50 and 55. There were four
      experimental groups: group 1--without chemoprevention, group 2--INDO treatment,
      group 3 --MEL treatment, group 4--application of INDO + MEL. The experiment
      lasted 26 weeks from the first administration of DMBA, when the final incidence
      and frequency of tumours per animal and group, as well as latency and average
      volume of tumours were evaluated. The content/concentration of malondialdehyde
      (MDA) was determined in selected tissues as a criterion of lipoperoxidation,
      considering its potential influencing by chemoprevention. The tumour incidence in
      controls was 100%; INDO reduced the incidence (36.84%) and frequency per group
      and animal, decreased the mean volume of tumours and prolonged the latency.
      Chemoprevention using combination of INDO with MEL was successful like that with
      INDO; however, it did not influence the tumour volume. MEL decreased the
      incidence to 42.11% and pronouncedly reduced the tumour frequency per group.
      INDO, administered alone or in combination with MEL, reduced an increased
      content/concentration of MDA in the liver, bone marrow and serum of tumour
      bearing rats. INDO, MEL and INDO + MEL had a pronounced chemopreventive effect
      and showed to be a favourable combination in prevention of experimental mammary
      carcinogenesis.

PMID- 11321253
TI  - A method for improving vaccination coverage in rural Tunisia.

PMID- 11321254
TI  - Rural men and their attitude towards vasectomy as means of contraception in
      Ethiopia.
AB  - A descriptive study on the attitude of rural men towards vasectomy as means of
      contraception was conducted in southwestern Ethiopia. A total of 200 men who came
      to a rural health centre either for treatment or to accompany a patient were
      included for interview. The mean age of the interviewees was 30.9 and the main
      occupation was farming (67.5%). The mean number of offspring born to the
      respondents was 3.5 with 70% of the respondents wanting more children. Fifty-five
      per cent had heard about contraception before and in this group 31% of the wives
      used or were using one of the common methods. None of the respondents was against
      the use of contraceptives and none of them had heard previously of vasectomy as
      means of contraception. The acceptance of vasectomy as means of contraception was
      79%. Twenty-one per cent opposed vasectomy because of the problem of possible
      loss of children due to death or divorce. The high acceptance rate of vasectomy
      indicates an unmet need for surgical contraception and the training of health
      personnel on the 'no scalpel vasectomy' technique. Making this service available,
      starting at health centre level, is recommended.

PMID- 11321255
TI  - Anaesthesia in rural Tanzania.
AB  - A survey of the anaesthetic services in rural Tanzania was carried out in an area
      of 67500 km2 and population of 4 million in order to assess the quality of
      anaesthesia and the major obstacles to good practice. Lack of draw-over
      vaporizers, Ayre's T-pieces, and a supply of oxygen were found to be the major
      obstacles to safe practice in this area of Africa.

PMID- 11321256
TI  - Management of enterocutaneous fistulae in Benin City Nigeria.
AB  - We report a prospective study of 17 cases of enterocutaneous fistulae managed at
      the University of Benin Teaching Hospital, Benin City, Nigeria between June 1992
      and June 1999. All the cases were iatrogenic in origin and all age groups (6
      weeks to 68 years, mean 27) were represented. There were 10 males and 7 females.
      Emergency surgery for acute appendicitis and intestinal obstruction were the
      commonest causes. Management should be conservative initially but surgery should
      be resorted to if there is no significant improvement, particularly in
      circumstances where facilities for total parenteral nutrition are not available.
      A literature review has been carried out and measures to prevent the development
      of enterocutaneous fistula are outlined.

PMID- 11321257
TI  - Three years' experience of empyema thoracis in association with HIV infection.

PMID- 11321258
TI  - Avoidable factors in maternal mortality following caesarean section (excluding
      ruptured uterus) in Calabar, Nigeria.

PMID- 11321259
TI  - Subacute sclerosing panencephalitis--a Pakistan perspective.
AB  - Subacute sclerosing panencephalitis (SSPE) remains a problem in areas of the
      world where measles virus is prevalent because of a lack of commitment to
      universal vaccination. We recently studied 89 cases compatible with a clinical
      diagnosis of SSPE and tested for antibody in serum or cerebrospinal fluid for
      measles virus. Eleven cases were confirmed to be SSPE on the basis of strongly
      supportive laboratory data.

PMID- 11321260
TI  - Ureteric fibrosis: a complication of guinea worm infestation of the
      retroperitoneum.

PMID- 11321261
TI  - Hydrocoele.

PMID- 11321262
TI  - Plagues of tomorrow and yesterday: emerging diseases in international health.

PMID- 11321263
TI  - Pitfalls of measuring smoking status.

PMID- 11321264
TI  - Intraosseous access in paediatric patients in a developing country setting.

PMID- 11321265
TI  - Small bowel perforation.

PMID- 11321267
TI  - New director for African Centre.

PMID- 11321266
TI  - Comparison of topical and intravenous lignocaine with thiopentone for insertion
      of laryngeal mask airway.

PMID- 11321268
TI  - Teenagers need access to safer sexual and reproductive health information and
      services.

PMID- 11321269
TI  - HIV testing: a practical approach.

PMID- 11321271
TI  - Blood safety.

PMID- 11321270
TI  - Unsafe injection practices.

PMID- 11321272
TI  - Adapting international protocols to local settings.

PMID- 11321273
TI  - Management of infantile hydrocephalus in Central Africa.
AB  - Hydrocephalus in children in the first year of life in the Central African
      countries of Malawi, Zambia and Zimbabwe is due mainly to congenital and
      infective causes. The children first present in hospital around the age of 3
      months. The clinical diagnosis is confirmed by cranial ultrasonography.
      Ventriculo-peritoneal CSF diversion is performed using locally made shunts
      (Harare, Malawi) which have given satisfactory results comparable to those from
      conventional shunts. The use of ETV should be explored for the future treatment
      of hydrocephalus as an alternative to shunting procedures.

PMID- 11321274
TI  - Influence of place of delivery on immediate perinatal outcomes: a study from
      Northern India.
AB  - One hundred and six women giving birth in a rural hospital in Northern India were
      compared with 100 women delivering in a tertiary care urban hospital located in
      an adjacent state. The women in the rural hospital were younger and more likely
      to be multiparous. Their antenatal course was characterized by fewer antenatal
      check-ups, significantly lower haemoglobin values, but equal weight gain during
      pregnancy. They were more likely to have a spontaneous vaginal delivery, and less
      likely to undergo caesarean section and episiotomy. Neonatal birth weights were
      lower in the rural group; other indices of neonatal well-being were comparable.

PMID- 11321275
TI  - Single-stage lumbar sympathectomy and omentopexy: a new surgical approach towards
      patients with Buerger's disease.
AB  - Single-stage lumbar sympathectomyand omentopexy were performed in six patients
      with Buerger's disease at the Department of Surgery, Jawahar Lal Nehru Medical
      College and Hospital, Ajmer, India, between January 1994 and December 1996. All
      were male smokers and had limb coldness, intermittent claudication and rest pain.
      Four had limb discoloration and three had ulcers of toes unresponsive to medical
      treatment. Postoperatively there was relief of symptoms in all, with improvement
      of tissue oxygen saturation and increase in claudication distance. We conclude
      that single-stage lumbar sympathectomy and omentopexy is an effective new
      surgical approach towards patients with Buerger's disease.

PMID- 11321276
TI  - Diagnosis of pneumonia by community health volunteers: experience of BRAC,
      Bangladesh.
AB  - The study assessed the validity of community health volunteers'diagnosis of
      pneumonia in children through simple clinical signs. Data were collected by a
      group of research physicians who observed the case management performance of 120
      health volunteers in Bangladesh where the Bangladesh Rural Advancement Committee
      has been providing community-based acute respiratory infection control since mid
      1992.1,166 children age 3-60 months were assessed at household level by both a
      community health volunteer and a research physician. Using physician diagnosis as
      gold standard, health volunteers'diagnosis of pneumonia was 67.6% sensitive and
      95.2% specific. Cohen's kappa for agreement between volunteers and physicians was
      0.67. Of the clinical signs elicited, chest in drawing and noisy breathing
      predicted physician's diagnosis of pneumonia most strongly ([positive predictive
      value (PPV)] 84% and 79%, respectively). The study concludes that less educated
      health volunteers can be effectively used in diagnosing pneumonia at grassroots
      level in developing countries.

PMID- 11321277
TI  - Open arthrolysis for functional restoration in post-traumatic elbow stiffness.
AB  - A prospective study of nine patients who had elbow stiffness after trauma and had
      open arthrolysis to restore function is presented: seven were children aged 6-10,
      two were adults--six males and three females. Five patients had supracondylar
      fracture as the initial lesion, one had posterior dislocation of the elbow and
      three had elbow sprains. They were all previously treated by native bonesetters
      and presented with elbow stiffness and fixed extension of the elbow. All had open
      arthrolysis using a posterior approach. The flexion range and loss of extension
      were measured pre-operatively and at 6 months after surgery using a goniometer.
      Both values were compared using the Student's t-tests for correlated samples.
      There was a significant improvement in the flexion range from a mean pre
      operative value of 3.6 degrees to 88.3 degrees post-operatively (t=8.87, P >
      0.01) and in the extension loss from a mean value of 33.8 degrees pre-operatively
      to 12.1 degrees post-operatively (t=7, P < 0.01). The improved flexion range was
      due to the operation while the improvement in the loss of extension was due to
      physiotherapy. Useful functional range of movement was restored in all patients.
      The operation is a very useful procedure and is recommended for patients with
      post-traumatic elbow stiffness when the elbow is fixed in the extended position.
      Best results are obtained if arthrolysis is done within 1 year of injury.

PMID- 11321278
TI  - An evaluation of on-site testing for syphilis.
AB  - One of the major obstacles to the eradication of perinatal transmission of
      syphilis is the delay in obtaining the results of syphilis serological tests. The
      availability of on-site syphilis testing lead to this study which attempted to
      evaluate on-site syphilis testing performed by nursing staff. The seroprevalence
      of syphilis by laboratory rapid plasma reagin (RPR) was 8.2% (n=42). Twenty-one
      of the 42 women were correctly identified by the on-site test. The overall
      sensitivity of on-site testing was 50% [95% confidence interval (CI)=34.4-65.6];
      specificity of 90.9% (95% CI=87.8-93.2). The on-site test correctly identified as
      uninfected 429 of the 471 women reported as RPR negative by the laboratory,
      giving a specificity of 91.1% (95% CI=88.1-93.4). The results of the study show
      that on-site RPR test had a sensitivity of 75% in respect of the clinically
      important titres of > or = 1:8. The specificity of the on-site test was 91.1% and
      on-site testing only failed to detect syphilis in those patients with titres of
      1:1 and 1:2. On-site testing is a practical and cost-effective option to prevent
      congenital syphilis, in settings of a high prevalence of syphilis and using
      skilled testers.

PMID- 11321279
TI  - Neurologic disease in a rural Zambian hospital.

PMID- 11321280
TI  - Prevalence of anaemia and iron deficiency in three trimesters in Rural Vellore
      district, South India.
AB  - A multistage sampling technique was used to select 845 pregnant women from two
      blocks in Vellore district. Haematological measurement of haemoglobin (Hb) was
      done on all women and serum ferritin (SF) on a subsample of 445. The prevalence
      of anaemia (Hb <11 g/dl) was 56.6%, 70.2% and 69.5%, respectively among the
      first, second and third trimester women. The mean Hb of 10.7 g/dl was
      significantly higher among the first trimester than among the second and third
      trimester women, which was less than the recommended value of 11 g/dl. Iron
      deficiency (SF <12 microg/L) was significantly (P< 0.05) more among the third
      trimester women than among the first. The high prevalence of anaemia in each
      trimester in pregnancy indicates the need for iron supplementation as early as
      possible starting from the fourth month of pregnancy.

PMID- 11321281
TI  - Perceptions, beliefs and practices of mothers in sub-urban and rural areas
      towards measles and measles vaccination in Northern Nigeria.
AB  - Measles is of particular concern in Nigeria because of the high fatality rate,
      and high morbidity rate, particularly in young children. Measles and its
      complications are a common reason for hospitalization, indicating very low
      immunization coverage. This study was carried out to elucidate the contributing
      factors from attitudes, beliefs and practices of mothers towards measles and its
      vaccination. A cross-sectional survey was conducted in Konduga Local Government
      Area. One per cent of the 500 mothers interviewed believed that measles is
      prevented by immunization, 16% that it is contagious or due to an infectious
      agent, 26% that it is caused by evil spirits, witchcraft and heat, and 25% had
      never heard of measles immunization. Twenty-seven per cent said they did not
      believe immunization was effective and 4% were not allowed to go for immunization
      by their husbands. Of those mothers whose children had developed measles, only
      31% had been treated in formal health facilities. These results indicate an
      unfavourable attitude and practice by mothers in relation to measles and measles
      vaccination. There is the need for an intensive health education campaign to
      improve this state of affairs and to reduce the morbidity and mortality from
      measles.

PMID- 11321282
TI  - A very low cost hospital electrical safety testing device used in north India.

PMID- 11321283
TI  - A modified technique of devascularization for surgical management of portal
      hypertension in children.
AB  - In developing countries surgery is indicated in patients with portal hypertension
      for a variety of reasons. This study prospectively evaluates a modified technique
      of devascularization for secondary prophylaxis of variceal bleeding in patients
      with portal hypertension of different aetiologies. Transabdominal extensive
      oesophagogastric devascularization combined with transmural ligation of
      oesophageal and gastric varices was performed in 16 paediatric patients (nine
      with extrahepatic portal venous obstruction, and seven with non-cirrhotic portal
      fibrosis) in an elective setting. The Sugiura devascularization procedure was
      modified to minimize the operating time and to avoid the problems associated with
      oesophageal transection and anastomosis. The operative mortality rate as well as
      the oesophageal leak rate was zero. One patient developed an oesophageal
      stricture. During a 12-month follow-up, patients were seen with residual varices
      (2), recurrent varices (3) and rebleeding (1). Porto-systemic encephalopathy was
      seen in one patient only. This technique is a simple, straightforward, safe and
      effective modification of the Sugiura procedure in controlling bleeding,
      providing good quality of life with minimal porto-systemic encephalopathy.

PMID- 11321284
TI  - Development of reactive onchocercal skin lesions during a placebo-controlled
      trial with ivermectin among persons without lesions at baseline.
AB  - Clinical trials of the effects of ivermectin on onchocercal skin disease have
      documented reduction in itching, but a less than clear benefit on reactive skin
      lesions. It has been suggested that one of the positive effects might be the
      prevention of new lesions. A study among a rural adult farming population in
      southwestern Nigeria provided ivermectin in three treatment groups and a placebo
      to community members who were examined and treated at 3-monthly intervals over a
      15-month period. Among the 1206 people recruited for the study, 627 (52%) had no
      lesions at baseline examination. Atotal of 291 participants without baseline
      lesions attended all five follow-up examinations, and only their results were
      analysed. Members of all four groups developed new lesions, but those receiving
      ivermectin had a consistently lower proportion of lesions than the placebo group.
      This difference reached statistical significance at the 5% level in three of the
      five periods and was below the 10% level at the other two periods. These findings
      are suggestive of an inhibiting effect of ivermectin among those without lesions
      at the beginning of a community treatment programme, and justify community
      treatment as a way of limiting morbidity and social stigma associated with these
      lesions.

PMID- 11321285
TI  - Fishing line: a valuable suture material.

PMID- 11321286
TI  - Nanoscale atmospheric pressure laser ablation-mass spectrometry.
AB  - We describe an atmospheric pressure nanosampling interface for mass spectrometry
      based on near-field laser ablation. Pulsed laser radiation is delivered to the
      sample surface through a near-field optical probe, and the ablation plume is
      sampled through a capillary orifice and analyzed by standard MS methods. A
      spatial resolution of less than 200 nm and a sensitivity below 2 amol is
      demonstrated.

PMID- 11321287
TI  - Detection of biotin in individual sea urchin oocytes using a bioluminescence
      binding assay.
AB  - The ability to detect biomolecules in single cells is important in order to fully
      understand the processes by which many biochemical events occur. To that end, we
      have developed a bioluminescence binding assay capable of measuring the
      intracellular biotin content of individual cells. The assay depends on
      competition between an aequorin-biotin conjugate (AEQ-biotin) and free biotin
      within the oocytes for binding sites on the protein avidin. The assay is
      performed by microinjecting each component into the oocytes and following the
      resulting bioluminescence within the oocyte upon triggering of aequorin. Results
      obtained using sea urchin oocytes show that the assay performed within the cells
      behaves in a manner consistent with assay theory. Using the assay, the individual
      biotin content of the oocytes is an average of approximately 20 amol. To our
      knowledge, this is the first reported multicomponent binding assay to be
      performed inside an intact single cell.

PMID- 11321288
TI  - Three-way analysis of fluorescence spectra of polycyclic aromatic hydrocarbons
      with quenching by nitromethane.
AB  - The application of trilinear decomposition (TLD) to the analysis of fluorescence
      excitation-emission matrices of mixtures of polycyclic aromatic hydrocarbons
      (PAHs) is described. The variables constituting the third-order tensor are
      excitation wavelength, emission wavelength, and concentration of a fluorescence
      quencher (nitromethane). The addition of a quencher to PAH mixtures selectively
      reduces the fluorescence intensity of mixture components according to the Stern
      Volmer equation. TLD allows the three-way matrix to be decomposed to give unique
      solutions for the excitation spectrum, emission spectrum, and quenching profiles
      for each component. The availability of spectra and calculated Stern-Volmer
      constants can aid in the identification of unknown components. Preprocessing of
      the data to correct for Rayleigh/Raman scatter and primary absorption by the
      quencher is necessary. Both three-component (anthracene, pyrene, 1-methylpyrene)
      and four-component (fluoranthene, anthracene, pyrene, 2,3-benzofluorene)
      synthetic mixtures are successfully resolved by TLD using quencher concentrations
      up to 100 mM. Results are compared using both alternating least-squares and
      direct trilinear decomposition algorithms. The reproducibility of extracted Stern
      Volmer constants is determined from replicate experiments. To illustrate the
      application of TLD to a real sample, a chromatographic cut from the analysis of a
      light gas oil sample was used. Analysis of the TLD extracted spectra and
      quenching constants suggests the presence of three classes of polycyclic aromatic
      hydrocarbons consistent with data from a second dimension of chromatography and
      mass spectrometry.

PMID- 11321289
TI  - A high-efficiency cross-flow micronebulizer for inductively coupled plasma mass
      spectrometry.
AB  - A pneumatically driven, high-efficiency cross-flow micronebulizer (HECFMN) is
      introduced for inductively coupled plasma (ICP) spectrometries. The HECFMN uses a
      smaller nozzle orifice for nebulizer gas (75 microm in diameter) and a
      replaceable and adjustable fused-silica capillary for sample uptake. The HECFMN
      is optimally operated over a wide range of sample uptake rate (5-120 microL/min)
      at a rf power of 1100 W and nebulizer gas flow rates of 0.8-1.0 L/min when a 50
      microm i.d. by 150 microm o.d. capillary is used. The aerosol quality is
      qualitatively examined in a simple manner, and the transport efficiencies are
      determined by direct filter collection. Compared with conventional cross-flow
      nebulizers (CFNs), the HECFMN produces much smaller and more uniform droplets and
      thus provides much higher analyte transport efficiencies (generally 24-95%) at
      the sample uptake rates of 5-100 microL/min. Several analytical performance
      indexes are acquired using an Ar ICPMS system. The sensitivities and detection
      limits measured with the HECFMN at 50 microL/min sample uptake rate are
      comparable to or improved over those obtained with a conventional CFN consuming 1
      mL/min sample, and the precisions with the HECFMN (typically 1.1-1.7% RSDs) are
      slightly better than those with the CFN (1.6-2.3% RSDs). The ratios of refractory
      oxide ion-to-singly charged ion (CeO+/Ce+) are typically in the range from 0.7 to
      3.3% for the sample uptake rates of 5-100 microL/min. The free aspiration rate of
      the HECFMN is 8.9 microL/min for distilled deionized water at the nebulizer gas
      flow rate of 1.0 L/min without any effect of pressure. The features of the HECFMN
      suggest good potential for HECFMN use in interfacing ICPMS with capillary
      electrophoresis and microcolumn high-performance liquid chromatography.

PMID- 11321290
TI  - Precise determination of mass-dependent variations in the isotopic composition of
      molybdenum using MC-ICPMS.
AB  - We present an analytical approach for the precise determination of mass-dependent
      differences in the isotopic composition of Mo between samples and reference
      standards using multiple-collector magnetic sector inductively coupled plasma
      mass spectrometry (MC-ICPMS). Either Zr or Ru "element spikes" are employed to
      correct for instrumental mass bias. Differences in 95Mo/97Mo can be determined to
      a precision of +/-0.2%o (+2sigma) using 1-10 microg of Mo. Similar precision is
      possible for other ratios after correction for isobaric interferences from either
      spike element. This approach facilitates study of mass-dependent variations in
      the isotopic composition of Mo in nature and in materials produced by laboratory
      processes. We observe fractionation of Mo isotopes of approximately 1.5%o/amu
      during ion-exchange chromatography in the laboratory and a shift of approximately
      0.3%o/amu between natural MoS2 and a laboratory standard.

PMID- 11321291
TI  - Chip-based quantitative capillary electrophoresis/mass spectrometry determination
      of drugs in human plasma.
AB  - A chip-based capillary electrophoresis/mass spectrometry (CE/MS) system is
      described for the on-chip separation and coupled electrospray detection of
      selected small drug molecule compounds. These studies include the quantitative
      determination of carnitine and acetylcarnitine in analytical standard solutions
      as well as imipramine and desipramine in fortified human plasma samples. A
      clinical human plasma sample was also analyzed following the normal
      administration of desipramine to a volunteer, and the parent drug was determined
      using the described chipbased CE/MS technique. In each instance, stable isotope
      incorporated internal standards were used. The chip-based CE system was
      microfabricated from glass and coupled to a micro ion spray device constructed in
      house. The atmospheric pressure ionization system employed in this work was a PE
      Sciex API III tandem triple quadrupole system operated in the selected ion
      monitoring (SIM) mode. The results from the work reported here demonstrate the
      feasibility for carrying out rapid (30 s) chipbased quantitative CE/MS
      determinations of samples containing small-molecule compounds. Using SIM CE/ MS
      techniques, the described API III quadrupole system provided acceptable ion
      current electropherograms from subpicomole levels of the targeted compounds
      loaded onto the chip. The corresponding electropherograms for the standard
      solution of carnitines at the 1-500 microg/mL level were obtained via SIM CE/MS
      techniques (R2 > 0.99). In addition, analyses of fortified samples of imipramine
      desipramine were measured relative to their corresponding d3 internal standards
      to obtain calibration curves ranging from 5 to 500 microg/mL in human plasma (R2
      > 0.99). The intra-assay precision ranged from 4.1 to 7.3% RSD. The intra-assay
      accuracy ranged from 94.0 to 104%. These results demonstrate the feasibility for
      on-chip CE separation and electrospray mass spectrometric determination in
      applications for bioanalytical measurements for these important compounds in
      synthetic mixtures and human plasma extracts.

PMID- 11321292
TI  - Detection of tyrosine phosphorylated peptides by precursor ion scanning
      quadrupole TOF mass spectrometry in positive ion mode.
AB  - Phosphorylation is a common form of protein modification. To understand its
      biological role, the site of phosphorylation has to be determined. Generally,
      only limited amounts of phosphorylated proteins are present in a cell, thus
      demanding highly sensitive procedures for phosphorylation site determination.
      Here, a novel method is introduced which enables the localization of tyrosine
      phosphorylation in gel-separated proteins in the femtomol range. The method
      utilizes the immonium ion of phosphotyrosine at m/z 216.043 for positive ion mode
      precursor ion scanning combined with the recently introduced Q2-pulsing function
      on quadrupole TOF mass spectrometers. The high resolving power of the quadrupole
      TOF instrument enables the selective detection of phosphotyrosine immonium ions
      without interference from other peptide fragments of the same nominal mass.
      Performing precursor ion scans in the positive ion mode facilitates sequencing,
      because there is a no need for polarity switching or changing pH of the spraying
      solvent. Similar limits of detection were obtained in this approach when compared
      to triple-quadrupole mass spectrometers but with significantly better
      selectivity, owing to the high accuracy of the fragment ion selection. Synthetic
      phosphopeptides could be detected at 1 fmol/microL, and 100 fmol of a tyrosine
      phosphorylated protein in gel was sufficient for the detection of the
      phosphorylated peptide in the unseparated digestion mixture and for unambiguous
      phosphorylation site determination. The new method can be applied to unknown
      protein samples, because the identification and localization of the modification
      is performed on the same sample.

PMID- 11321293
TI  - Automated high-throughput infusion ESI-MS with direct coupling to a microtiter 
      plate.
AB  - This paper describes the design and application of instrumentation for automated
      high-throughput infusion ESI-mass spectrometry. The approach, based on a
      subatmospheric ESI interface, allows sample introduction from a commercially
      available microtiter plate without the need for a separate fluid delivery system.
      The microtiter plate was placed vertically on a three-dimensional translation
      stage in front of the sampling ESI interface. A single, 7-cm, 20-microm-i.d.
      fused-silica capillary (total volume, 70 nL), with a tapered tip, served as a
      combination of sample delivery and spraying capillary. The tapered tip of the
      capillary was enclosed in a subatmospheric chamber attached in front of the
      orifice of the mass spectrometer. The sample aspiration rate (flow rate) was
      regulated by computer-controlled pneumatic valves, which allowed fast switching
      of the pressure in the subatmospheric ESI chamber. A flow-through wash device was
      positioned between the microtiter plate and the ESI interface. This design
      allowed alternate filling of the capillary with (a) sample from the wells and (b)
      wash solution from the wash device. Sample turnaround times of 10 s/sample, with
      a 120-nL sample consumption/analysis, and a duty cycle (percentage of total
      analysis time spent acquiring data) of 40% were achieved. The infusion system was
      demonstrated in the analysis of preparative HPLC fractions from a small molecule
      combinatorial library.

PMID- 11321294
TI  - Supercharged protein and peptide ions formed by electrospray ionization.
AB  - The multiple charging of large molecules in electrospray ionization provides key
      advantages for obtaining accurate molecular weights by mass spectrometry and for
      obtaining structural information by tandem mass spectrometry and MS(n)
      experiments. Addition of glycerol or m-nitrobenzyl alcohol into the electrospray
      solutions dramatically increases both the maximum observed charge state and the
      abundances of the high charge states of protein and peptide ions. Adding glycerol
      to acidified aqueous solutions of cytochrome c shifts the most abundant charge
      state from 17+ to 21+, shifts the maximum charge state from 20+ to 23+, and
      shifts the average charge state from 16.6+ to 20.9+. Much less m-nitrobenzyl
      alcohol (<1%) is required to produce similar results. With just 0.7% m
      nitrobenzyl alcohol, even the 24+ charge state of cytochrome c is readily
      observed. Similar results are obtained with myoglobin and (Lys)4. For the latter
      molecule, the 5+ charge state is observed in the electrospray mass spectrum
      obtained from solutions containing 6.7% m-nitrobenzyl alcohol. This charge state
      corresponds to protonation of all basic sites in this peptide. Although the
      mechanism for enhanced charging is unclear, it does not appear to be a
      consequence of conformational changes of the analyte molecules. This method of
      producing highly charged protein ions should be useful for improving the
      performance of mass measurements on mass spectrometers with performances that
      decrease with increasing m/z. This should also be particularly useful for tandem
      mass spectrometry experiments, such as electron capture dissociation, for which
      highly charged ions are desired.

PMID- 11321295
TI  - Molecular resolution and fragmentation of fulvic acid by electrospray
      ionization/multistage tandem mass spectrometry.
AB  - Molecular weight distributions of fulvic acid from the Suwannee River, Georgia,
      were investigated by electrospray ionization/quadrupole mass spectrometry (ESI/
      QMS), and fragmentation pathways of specific fulvic acid masses were investigated
      by electrospray ionization/ion trap multistage tandem mass spectrometry (ESI/MST/
      MS). ESI/QMS studies of the free acid form of low molecular weight
      poly(carboxylic acid) standards in 75% methanol/25% water mobile phase found that
      negative ion detection gave the optimum generation of parent ions that can be
      used for molecular weight determinations. However, experiments with poly(acrylic
      acid) mixtures and specific high molecular weight standards found multiply
      charged negative ions that gave a low bias to molecular mass distributions. The
      number of negative charges on a molecule is dependent on the distance between
      charges. ESI/MST/MS of model compounds found characteristic water loss from
      alcohol dehydration and anhydride formation, as well as CO2 loss from
      decarboxylation, and CO loss from ester structures. Application of these
      fragmentation pathways to specific masses of fulvic acid isolated and fragmented
      by ESI/MST/MS is indicative of specific structures that can serve as a basis for
      future structural confirmation after these hypothesized structures are
      synthesized.

PMID- 11321296
TI  - Development of a multichannel microfluidic analysis system employing affinity
      capillary electrophoresis for immunoassay.
AB  - A six-channel microfluidic immunoassay device with a scanned fluorescence
      detection system is described. Six independent mixing, reaction, and separation
      manifolds are integrated within one microfluidic wafer, along with two optical
      alignment channels. The manifolds are operated simultaneously and data are
      acquired using a singlepoint fluorescence detector with a galvano-scanner to step
      between separation channels. A detection limit of 30 pM was obtained for
      fluorescein with the scanning detector, using a 7.1-Hz sampling rate for each of
      the reaction manifolds and alignment channels (57-Hz overall sampling rate).
      Simultaneous direct immunoassays for ovalbumin and for anti-estradiol were
      performed within the microfluidic device. Mixing, reaction, and separation could
      be performed within 60 s in all cases and within 30 s under optimized conditions.
      Simultaneous calibration and analysis could be performed with calibrant in
      several manifolds and sample in the other manifolds, allowing a complete
      immunoassay to be run within 30 s. Careful chip conditioning with methanol,
      water, and 0.1 M NaOH resulted in peak height RSD values of 3-8% (N = 5 or 6),
      allowing for cross-channel calibration. The limit of detection (LOD) for an anti
      estradial assay obtained in any single channel was 4.3 nM. The LOD for the cross
      channel calibration was 6.4 nM. Factors influencing chip and detection system
      design and performance are discussed in detail.

PMID- 11321297
TI  - Determination of vaporization enthalpies of polychlorinated biphenyls by
      correlation gas chromatography.
AB  - The vaporization enthalpies of 16 polychlorinated biphenyls have been determined
      by correlation gas chromatography. This study was prompted by the realization
      that the vaporization enthalpy of the standard compounds used in previous
      studies, octadecane and eicosane, were values measured at 340 and 362 K,
      respectively, rather than at 298 K. Adjustment to 298 K amounts to a 7-8 kJ/mol
      increment in the values. With the inclusion of this adjustment, vaporization
      enthalpies evaluated by correlation gas chromatography are in good agreement with
      the values determined previously in the literature. The present results are based
      on the vaporization enthalpies of several standards whose values are well
      established in the literature. The standards include a variety of n-alkanes and
      various chlorinated hydrocarbons. The vaporization enthalpies of PCBs increased
      with the number of chlorine atoms and were found to be larger for meta- and para
      substituted polychlorinated biphenyls.

PMID- 11321298
TI  - Picogram determination of "earthly-musty" odorous compounds in water using
      modified closed loop stripping analysis and large volume injection GC/MS.
AB  - "Earthy-musty" off-flavor problems in water samples are due to organic compounds
      present at the sub-part-per-trillion level. Numerous analytical methods such as
      purge and trap, liquid/liquid extraction, and closed-loop stripping analysis
      (CLSA) followed by GC/MS analysis have been used to determine these compounds.
      However, these methods offer poor sensitivity (detection limits of approximately
      1 to 10 ng/L) when compared to the 20-30 pg/L of sensorial sensitivity. The
      purpose of this study was to develop a new method involving a modified CLSA
      preconcentration technique together with large volume injection GC/MS in order to
      attain analytical sensitivity equal to or better than olfactory sensitivity. For
      eight target compounds that cause taste and odor problems in water at trace
      levels, the method developed was linear in the 0.05-10 ng/L range and provided
      recoveries greater than 70% together with satisfactory repeatability. Detection
      limits as low as 15-30 pg/L were achieved, representing a 50-fold improvement in
      sensitivity as compared to current methods. The accuracy and sensitivity of the
      method were demonstrated in different aqueous matrixes, including raw surface
      water. The method was successfully applied to earthy-musty water samples that had
      remained unsolved by conventional techniques, thus proving its effectiveness.

PMID- 11321299
TI  - High-performance liquid chromatography linked to inductively coupled plasma mass
      spectrometry and orthogonal acceleration time-of-flight mass spectrometry for the
      simultaneous detection and identification of metabolites of 2-bromo-4
      trifluoromethyl.
AB  - The use of HPLC coupled to inductively coupled plasma mass spectrometry (ICPMS)
      and orthogonal acceleration time-of-flight (oa-TOF) for the profiling,
      identification, and quantification of metabolites in rat urine following the
      administration of 2-bromo-4-trifluoromethylacetanilide is described. The
      metabolites present in the sample were separated by reversed-phase gradient
      chromatography with UV-diode array detection. The bulk of the eluent (90%) from
      the UV detector was directed to an ICPMS where bromine-containing metabolites
      were detected and quantified using ICPMS. The minor portion of the eluent (10%)
      was taken for oa-TOFMS for identification. By these means, the metabolites were
      identified as sulfate and glucuronide conjugates of a ring hydroxy-substituted
      metabolite, a N-sulfate, a N-hydroxylamine glucuronide, and N- and N
      hydroxyglucuronides.

PMID- 11321300
TI  - A high-capacity LC/MS system for the bioanalysis of samples generated from plate
      based metabolic screening.
AB  - HPLC/MS is a linear technique characterized by serial injection and analysis of
      individual samples. Parallel-format high-throughput screens for druglike
      properties present a significant analytical challenge. Analysis speed and system
      ruggedness are key requirements for bioanalysis of thousands of samples per day.
      The tasks involved in LC/MS analysis are readily divided into three areas, sample
      preparation/liquid handling, LC/MS method building/sample analysis, and data
      processing. Several automation and multitasking strategies were developed and
      implemented to minimize plating and liquid handling errors, reduce dead times
      within the analysis cycle, and allow for comprehensive review of data. Delivering
      multiple samples to multiple injectors allows the autosampler time to complete
      its wash cycles and aspirate the next set of samples while the previous set is
      being analyzed. A dual-column chromatography system provides column cycling and
      peak stacking and allows rapid throughput using conventional LC equipment.
      Collecting all data for a compound into a single file greatly reduces the number
      of data files collected, increases the speed of data collection, allows rugged
      and complete review of all data, and provides facile data management. The
      described systems have analyzed over 40 000 samples per month for two years and
      have the capacity for over 2000 samples per instrument per day.

PMID- 11321301
TI  - On-line process control of liquid chromatography.
AB  - Many analytical methods are based on liquid chromatography and typically the only
      measure of system stability is standards, injected repeatedly throughout the
      sequence. In this paper, a novel approach is presented, where the analytical run
      is treated as a process with the chromatographic data as the product. It is
      postulated that enhanced quality of the data can be obtained through monitoring
      the process, i.e., the chromatographic system, during the sequence. For this
      purpose, a liquid chromatography process control (LCPC) system has been
      developed. Here, several parameters, e.g., the pressure at the column and the
      injection valve, are monitored. Chemometrics is used for interpreting the data
      and producing multivariate statistical process control (MSPC) charts. The
      chromatographic run is divided into two parts: the dynamic injection phase and
      the static elution phase. Two principal component analysis (PCA) models, one for
      each phase, are continuously created and upgraded as the data are collected. The
      results of the PCA are shown in the MSPC charts, and when an error detection
      limit is exceeded, the analyst is promptly notified. LCPC, a continuous system
      suitability test, provides better control of the analysis, allowing a reduction
      in the number of standards and replicates. Furthermore, troubleshooting is
      facilitated.

PMID- 11321302
TI  - Stir bar sorptive extraction for the determination of ppq-level traces of
      organotin compounds in environmental samples with thermal desorption-capillary
      gas chromatography--ICP mass spectrometry.
AB  - The extraction and preconcentration capabilities of a new extraction technique,
      stir bar sorptive extraction, were combined with the separation power of
      capillary gas chromatography (CGC) and the low limits of detection (LODs) of
      inductively coupled plasma mass spectrometry (ICPMS) for the determination of the
      organotin compounds tributyltin (TBuT) and triphenyltin (TPhT) in aqueous
      standard solutions, harbor water, and mussels (after digestion with
      tetramethylammonium hydroxide). Throughout, tripropyltin for TBuT and
      tricyclohexyltin for TPhT were used as internal standards to correct for
      variations in the derivatization and extraction efficiency. Calibration was
      accomplished by means of single standard addition. Derivatization to transform
      the trisubstituted compounds into sufficiently volatile compounds was carried out
      with sodium tetraethylborate. The compounds were extracted from their aqueous
      matrix using a stir bar of 1-cm length, coated with 55 microL of
      poly(dimethylsiloxane) (PDMS). After 15 min of extraction, the stir bar was
      desorbed in a thermal desorption unit at 290 degrees C for 15 min, during which
      the compounds were cold-trapped on a precolumn at -40 degrees C. Flash heating
      was used to rapidly transfer the compounds to the GC where they were separated on
      a capillary column with a PDMS coating. After separation, the compounds were
      transported to the ICP by means of a homemade heated (270 degrees C) transfer
      line. Monitoring of the 120Sn+ signal by ICPMS during the run of the GC provided
      extremely low LODs for TPhT in water: 0.1 pg L(-1) (procedure) and 10 fg L(-1)
      (instrumental) and a repeatability of 12% RSD (n = 10). In harbor water,
      concentrations of 200 pg L(-1) for TBuT and 22 pg L(-1) for TPhT were found. In
      fresh mussels, a concentration of 7.2 ng g(-1) (dry weight) TPhT was found. The
      accuracy of the method was checked by the determination of TPhT in CRM477 (mussel
      tissue) and comparison of the result to that of an analysis of the same material
      with a classical liquid/liquid extraction with isooctane.

PMID- 11321303
TI  - High-temperature, microwave-assisted UV digestion: a promising sample preparation
      technique for trace element analysis.
AB  - A novel, microwave-assisted, high-temperature UV digestion procedure was
      developed for the accelerated decomposition of interfering dissolved organic
      carbon (DOC) prior to trace element analysis of liquid samples such as,
      industrial/municipal wastewater, groundwater, and surface water, body fluids,
      infusions, beverages, and sewage. The technique is based on a closed,
      pressurized, microwave digestion device. UV irradiation is generated by immersed
      electrodeless Cd discharge lamps (228 nm) operated by the microwave field in the
      oven cavity. To enhance excitation efficiency an antenna was fixed on top of the
      microwave lamp. The established immersion system enables maximum reaction
      temperatures up to 250-280 degrees C, resulting in a tremendous increase of
      mineralization efficiency. Compared to open UV digestion devices, decomposition
      time is reduced by a factor of 5 and the maximum initial concentration of DOC can
      be raised by at least a factor of 50. The system's performance on a real-type
      sample was evaluated for the mineralization of skimmed milk (IRMM, CRM 151) and
      subsequent determination of trace elements using standard spectroscopic
      techniques. Recovery for Cd (109%), Cu (112%), Fe (99%), and Pb (96%) showed good
      agreement with the 95% confidence interval of the certified values.

PMID- 11321304
TI  - Development of highly fluorescent detection reagents for the construction of
      ultrasensitive immunoassays.
AB  - We developed two kinds of highly fluorescent streptavidin-based conjugates for
      use as universal detection reagents in ultrasensitive immunoassays. The direct
      conjugate was produced by covalently linking streptavidin to poly(Glu: Lys) which
      was labeled heavily with Eu chelates; the indirect conjugate was made by first
      conjugating bovine serum albumin (BSA) to poly(Glu:Lys) labeled heavily with Eu
      chelates and then further linking streptavidin to the conjugate of BSA
      poly(Glu:Lys)-Eu chelate. Both direct and indirect conjugates were used to
      construct a highly sensitive time-resolved fluorometric assay for prostate
      specific antigen (PSA). Of two monoclonal antibodies used in the assay, one was
      coated on the well surface of the microtitration strips, and the other was
      biotinylated. When 10 microL of sample volume was used, we found that the assay
      using the indirect conjugate had a detection limit of 0.006 microg/L, which was
      approximately 5.6-fold more sensitive than the one using Eu chelate directly
      labeled detection antibody and 6.8-fold more sensitive than the one using Eu
      chelate-labeled streptavidin. However, the assay that used the direct conjugate
      was 1.5-fold more sensitive than the one that utilized the indirect conjugate.
      When 45 microL of sample volume was used, a detection limit of 0.001 microg/L was
      achieved by using the direct conjugate. This improvement in sensitivity should be
      equally obtainable for the analytes other than PSA. We further demonstrated that
      the final immunoassay performance was affected not only by the quality of the
      streptavidin-based conjugate used but also by the quality of the biotinylated
      antibody reagent. The universal detection reagents described here are believed to
      be particularly useful for the construction of ultrasensitive time-resolved
      fluorometric immunoassays and are potentially applicable in other fields such as
      immunohistochemistry and nucleic acid detection.

PMID- 11321305
TI  - Boronic acid fluorophore/beta-cyclodextrin complex sensors for selective sugar
      recognition in water.
AB  - A novel boronic acid fluorophore 1/beta-cyclodextrin (beta-CyD) complex sensor
      for sugar recognition in water has been designed. The probe 1 bearing pyrene
      moiety as a fluorescent signal transducer exhibits no fluorescence emission, due
      to its aggregation in water containing 2% DMSO; however, the addition of beta-CyD
      to this solution largely changes UV-vis and fluorescence spectra of 1 by forming
      an inclusion complex with beta-CyD, and an efficient fluorescence emission
      response of 1/beta-CyD complex upon sugar binding is found to be obtained at pH
      7.5. The pH-fluorescence profile of the 1/beta-CyD complex reveals that the
      boronate ester formation with fructose induces the apparent pKa shift from 7.95+/
      0.03 in the absence of fructose to 6.06+/-0.03 in the presence of 30 mM fructose,
      resulting in the fluorescence emission response under the neutral condition. The
      spectral properties of 1 in 95% methanol:5% water (v/v), as well as the
      fluorescence quenching study of 1-methylpyrene with 4-methoxycarbonylphenyl
      boronic acid 2, demonstrate that the response mechanism is based on the
      photoinduced electron transfer (PET) from the pyrene donor to the acid form of
      phenylboronic acid acceptor in 1, and thus, the proton dissociation of
      phenylboronic acid induced by sugar binding inhibits the PET system while
      increasing the fluorescence intensity of the pyrene moiety. To evaluate the
      binding ability and selectivity of the 1/beta-CyD complex for monosaccharides in
      water, the response equilibria have been derived. The 1:1 binding constants of
      the 1/beta-CyD complex obtained from the equilibrium analysis are in the order: D
      fructose (2515+/-134 M(-1)) >> L-arabinose (269 +/- 28 M(-1)) > D-galactose
      (197+/-28 M(-1)) > D-glucose (79+/-33 M(-1)), which is consistent with the
      binding selectivity of phenylboronic acid.

PMID- 11321306
TI  - Selective detection of individual DNA molecules by capillary polymerase chain
      reaction.
AB  - On-line capillary polymerase chain reaction (PCR) coupled with laser-induced
      fluorescence detection was successfully demonstrated for individual DNA
      molecules. A single 30-microm-i.d. fused-silica capillary was used both as the
      reaction vessel and for isolating single molecules. SYBR green I dye was added
      into the reaction mixture for dynamic fluorescent labeling. Because of the small
      inside diameter of the capillary, PCR-amplified DNA fragments from single
      molecules were localized in the capillary, providing discrete product zones with
      concentrations at readily detectable levels. By counting the number of peaks in
      the capillary via electromigration past a detection window, the number of
      starting DNA molecules could be determined. With selective primer design, only
      the molecule of interest was detected. Amplification of the 110-bp fragment from
      an individual human beta-globin gene and the 142-bp fragment from an individual
      HIV-1 DNA was demonstrated. This opens the possibility of highly selective and
      sensitive disease diagnosis at a very early stage.

PMID- 11321307
TI  - Analysis of viral glycoproteins by MALDI-TOF mass spectrometry.
AB  - Membrane glycoproteins were shown to be useful biomarkers of enveloped viruses
      using on-target deglycosylation and matrix-assisted laser desorption/ionization
      time-of-flight mass spectrometry (MALDI-TOF MS). Sindbis virus, the prototype
      alpha-virus, was used as a model system. The glycoproteins and the capsid protein
      of the Sindbis virus were successfully detected by MALDI-TOF MS using two solvent
      systems. One of them is 0.5% n-octyl glucoside/0.5% trifluoroacetic acid. The two
      components of this solvent acted synergistically on the virus to help release and
      solubilize the structural proteins. The other is 70% acetonitrile/30% formic
      acid. This solvent solubilized the integral membrane glycoproteins very
      effectively even after serious aggregation. On-target deglycosylation was
      performed to confirm the detection of the glycoprotein peak and to produce
      protein moieties that can be used as biomarkers. After a simple and fast
      incubation using peptide-N-glycosidase F on target, sequential mass shifts were
      observed, which proved that the proteins detected at 51 000 Da have N-linked
      carbohydrate moieties at two sites. Observation of this mass shift could provide
      confirmatory evidence for viral identification.

PMID- 11321308
TI  - Electric manipulation of bioparticles and macromolecules on microfabricated
      electrodes.
AB  - Bioparticle separation, bioparticle enrichment, and electric field-mediated
      immune detection were carried out on microfabricated semiconductor chips
      utilizing ac and dc electric fields. Microscale separation on a chip surface
      having an active area of approximately 16 mm2 was demonstrated for a mixture of
      Bacillus globigii spores and Escherichia coli bacteria. Dielectrophoretic
      enrichment was performed by collecting target bioparticles from a flow stream in
      flow cells of 47.5 microL, achieving a 20-fold increase in the concentration of
      E. coli bacteria from a diluted sample, a 28-fold enrichment for peripheral blood
      mononuclear cells from red blood cells, and a 30-fold increase in white blood
      cells from diluted whole blood. The ability to manipulate and collect
      bioparticles and macromolecules at microfabricated electrodes with ac and dc
      fields was further illustrated in electric field-mediated immunoassays for
      analyzing the biological identities of E. coli bacteria and B. globigii spores.
      According to these results, the electric methods for manipulating bioparticles
      present themselves as viable techniques for novel biomedical applications in
      sample preparations and biochemical assays on microelectrode arrays.

PMID- 11321309
TI  - Mammalian cell cultures on micropatterned surfaces of weak-acid, polyelectrolyte
      hyperbranched thin films on gold.
AB  - A four-step soft lithographic process based on micro-contact printing of organic
      monolayers, hyperbranched polymer grafting, and subsequent polymer
      functionalization results in polymer/n-alkanethiol patterns that direct the
      growth and migration of mammalian cells. The functional units on these surfaces
      are three-dimensional cell "corrals" that have walls 52+/-2 nm in height and
      lateral dimensions on the order of 60 microm. The corrals have hydrophobic,
      methyl-terminated n-alkanethiol bottoms, which promote cell adhesion, and walls
      consisting of hydrophilic poly(acrylic acid)/poly(ethylene glycol) layered
      nanocomposites that inhibit cell growth. Cell viability studies indicate that
      cells remain viable on the patterned surfaces for up to 21 days, and fluorescence
      microscopy studies of stained cells demonstrate that cell growth and spreading
      does not occur outside of the corral boundaries. This simple, chemically flexible
      micropatterning method provides spatial control over growth of IC-21 murine
      peritoneal macrophages, human umbilical vein endothelial cells, and murine
      hepatocytes.

PMID- 11321310
TI  - Cantilever-based optical deflection assay for discrimination of DNA single
      nucleotide mismatches.
AB  - Characterization of single-nucleotide polymorphisms is a major focus of current
      genomics research. We demonstrate the discrimination of DNA mismatches using an
      elegantly simple microcantilever-based optical deflection assay, without the need
      for external labeling. Gold-coated silicon AFM cantilevers were functionalized
      with thiolated 20- or 25-mer probe DNA oligonucleotides and exposed to target
      oligonucleotides of varying sequence in static and flow conditions. Hybridization
      of 10-mer complementary target oligonucleotides resulted in net positive
      deflection, while hybridization with targets containing one or two internal
      mismatches resulted in net negative deflection. Mismatched targets produced a
      stable and measurable signal when only a four-base pair stretch was complementary
      to the probe sequence. This technique is readily adaptable to a high-throughput
      array format and provides a distinct positive/negative signal for easy
      interpretation of oligonucleotide hybridization.

PMID- 11321311
TI  - Ultrasensitive detection of CrO4(2-) using a microcantilever sensor.
AB  - Microcantilevers modified with a self-assembled monolayer respond sensitively to
      specific ion concentrations. Here, we report the detection of trace amounts of
      CrO4(2-) using microcantilevers modified with a self-assembled monolayer of
      triethyl-12-mercaptododecylammonium bromide. The self-assembled monolayer was
      prepared on a silicon microcantilever coated with a thin layer of gold on one
      side. The microcantilever undergoes bending due to sorption of CrO4(2-) ions on
      the monolayer-modified side. It was found that a concentration of 10(-9) M CrO4(2
      ) can be detected using this technology in a flow cell. Other anions, such as Cl
      , Br-, CO3(2-) (or HCO3-), and SO4(2-), have minimal effect on the deflection of
      this cantilever. The mechanics of the bending and the chemistry of cantilever
      modification are discussed.

PMID- 11321312
TI  - A strategy for chemical sensing based on frequency tunable acoustic devices.
AB  - A new acoustic sensor geometry, the magnetic acoustic resonant sensor (MARS), is
      described. The device comprises a circular 0.5-mm-thick resonant plate fabricated
      from a wide variety of nonpiezoelectric materials and coated on the underside
      with a 2.5-microm-thick aluminum film. Harmonic radial shear waves over at least
      a 2 orders of magnitude frequency range can be induced in the resonant plate by
      enhanced magnetic direct generation using a noncontacting rf coil and NdFeB
      magnet. Mass loading with adherent aluminum films produced frequency changes of
      106 Hz/nm (40.8 Hz/ng-mm(-2)), while contact with viscous fluids resulted in
      maximum changes of 15 446 Hz/cP. At an operating frequency of 50 MHz, the device
      detected viscosity changes as low as 0.0006 cP. The adsorption of proteins such
      as human IgG and the binding of a complementary antigen, goat anti-human IgG, on
      the upper nonmetallized surface of the device has been monitored with a detection
      limit of approximately 75 ng/mL. The binding of substrates and allosteric
      effectors to glycogen phosphorylase b has provided evidence that the device is
      very sensitive to viscoelastic changes in adsorbed proteins. The MARS device
      generates radial shear acoustic waves over a broad bandwidth that are unaffected
      by the conductivity of the solution. These results suggest that simple metal,
      glass, crystalline, or polycrystalline plates can be used as a new type of
      tunable acoustic immunosensor.

PMID- 11321313
TI  - Resolving factor analysis.
AB  - Bilinear data matrices may be resolved into abstract factors by factor analysis.
      The underlying chemical processes that generated the data may be deduced from the
      abstract factors by hard (model fitting) or soft (model-free) analyses. We
      propose a novel approach that combines the advantages of both hard and soft
      methods, in that only a few parameters have to be fitted, but the assumptions
      made about the system are very general and common to a range of possible models:
      The true chemical factors span the same space as the abstract factors and may be
      mapped onto the abstract factors by a transformation matrix T, since they are a
      linear combination of the abstract factors. The difference between the true
      factors and any other linear combination of the abstract factors is that the true
      factors conform to known chemical constraints (for instance, nonnegativity of
      absorbance spectra or monomodality of chromatographic peaks). Thus, by excluding
      linear combinations of the abstract factors that are not physically possible
      (assuming a unique solution), we can find the true chemical factors. This is
      achieved by passing the elements of a transformation matrix to a nonlinear
      optimization routine, to find the best estimate of T that fits the criteria. The
      optimization routine usually converges to the correct minimum with random
      starting parameters, but more difficult problems require starting parameters
      based on some other method, for instance EFA. We call the new method resolving
      factor analysis (RFA). The use of RFA is demonstrated with computer-generated
      kinetic and chromatographic data and with real chromatographic (HPLC) data. RFA
      produces correct solutions with data sets that are refractory to other methods,
      for instance, data with an embedded nonconstant baseline.

PMID- 11321314
TI  - Detection of electrochemical enzymatic reactions by surface plasmon resonance
      measurement.
AB  - We describe the surface plasmon resonance (SPR) detection of an enzymatic
      turnover reaction and the measurement of glucose concentration using a
      multienzyme layer modified gold electrode. We constructed an osmium redox polymer
      mediated enzyme sensor on a gold thin-film electrode and monitored
      electrochemical reaction by SPR measurement. Unlike the usual binding assay with
      SPR, here we used SPR to detect the redox state of an electron mediator that was
      the result of the electron-transfer reaction of sequential enzymatic reactions.
      Therefore, the degree of refractive index change was independent of the
      dielectric property of the substrate and enzymatic molecular recognition was
      converted to refractive index change with amplification. For the quantitative
      evaluation of glucose with this method, we used chronopotentiometry and a linear
      relation was obtained between the glucose concentration and the rate of
      refractive index change.

PMID- 11321315
TI  - Combinatorial discovery of alloy electrocatalysts for amperometric glucose
      sensors.
AB  - Combinatorial methods were used to search for active alloy electrocatalysts for
      use in enzyme-free amperometric glucose sensors. Electrode arrays (715-member)
      containing combinations of Pt, Pb, Au, Pd, and Rh were prepared and screened by
      converting anodic current to visible fluorescence. The most active compositions
      contained both Pt and Pb. Bulk quantities of catalysts with compositions
      corresponding to those identified in the screening experiments were prepared and
      characterized. The best alloy electrocatalysts catalyzed glucose oxidation at
      substantially more negative potentials than pure platinum in enzyme-free
      voltammetric measurements. They were also insensitive to potential interfering
      agents (ascorbic and uric acids, and 4-acetamidophenol), which are oxidized at
      slightly more positive potentials. Rotating disk electrode (RDE) experiments were
      carried out to study the catalytic mechanism. The improvement in catalytic
      performance was attributed to the inhibition of adsorption of oxidation products,
      which poison Pt electrodes.

PMID- 11321316
TI  - SoI--gel modification of pH electrode glass membranes for sensing anions and
      metal ions.
AB  - To obtain glass membrane electrodes selective for anions and metal ions, pH
      electrode glass membranes were modified by a sol-gel method using a quaternary
      ammonium salt and a bis(crown ether). A chloride ion-sensing glass membrane was
      designed, in which a pH electrode glass membrane was modified chemically by an
      alkoxysilyl quaternary ammonium chloride. X-ray photoelectron spectroscopy
      confirmed the chemical bonding of the quaternary ammonium moiety to the starting
      glass surface, which afforded the first example of glass-based "anion"-sensing
      membranes. A neutral carrier-type sodium ion-selective glass membrane was also
      fabricated which encapsulates a bis(12-crown-4) derivative in its sol-gel-derived
      surface. Both sol-gel-modified anion and metal ion-selective glass electrodes
      exhibited high sensitivity to their ion activity changes. The present sol-gel
      modification paves the way for designing glass-based ion sensors with tailor-made
      ion selectivities toward anions as well as cations.

PMID- 11321317
TI  - Attomole-level protein fingerprinting based on intrinsic peptide fluorescence.
AB  - Protein identification has relied heavily on proteolytic analysis, but current
      techniques are often slow and generally consume large quantities of valuable
      protein sample. We report the development of a rapid, ultralow volume protein
      analysis strategy based on tryptic digestion within the tip of a 1.5-microm
      capillary channel followed by separation of the proteolytic fragments using
      capillary electrophoresis (CE). Two-photon excitation is used to probe the
      intrinsic fluorescence of peptide fragments through "deep-UV" excitation of
      aromatic amino acid residues at the outlet of the CE channel. Detection limits
      using this technique are 0.7, 2.4, and 23 amol for the aromatic amino acids
      tryptophan, tyrosine, and phenylalanine, respectively. In these studies, we
      demonstrate the capacity to differentiate bovine and yeast cytochrome c variants
      using less than 15 amol of protein through tryptic fingerprinting. Moreover, the
      detection of a single amino acid substitution between bovine and canine
      cytochrome c illustrates the sensitivity of this approach to minor differences in
      protein sequence. The 2-pL sample volume required for this on-column tryptic
      digestion is, to our knowledge, the smallest yet reported for a proteolytic
      assay.

PMID- 11321318
TI  - Simultaneous determination of five beta-lactam antibiotics in bovine milk using
      liquid chromatography coupled with electrospray ionization tandem mass
      spectrometry.
AB  - A multiresidue method for the detection of five important beta-lactam antibiotics
      (amoxicillin, ampicillin, cloxacillin, oxacillin, penicillin G) in fresh milk is
      presented that allows quantitation of the analytes well below established
      legislative limits. The method avoids the use of acid during the extraction
      procedure and entails a cleanup step over a C18 cartridge. The analytes are
      separated and detected by liquid chromatography-electrospray ionization tandem
      mass spectrometry (LC-ESI-MS/MS) using a stable isotope-labeled internal
      standard. Mass spectral acquisition is done in the positive ion mode by applying
      selected reaction monitoring of two or more fragmentation transitions per analyte
      to provide a high degree of sensitivity and specificity. The typical recoveries
      for all five beta-lactams in fresh milk ranged from 76 to 94% at a fortification
      level of 4 microg/kg. This study also addresses common problems encountered in
      the stability of penicillins during sample preparation as well as the employment
      of postcolumn infusion of a standard compound to verify potential matrix-induced
      signal suppression in ESI-MS.

PMID- 11321319
TI  - Monolithic capillary electrophoresis device with integrated fluorescence
      detector.
AB  - A monolithic capillary electrophoresis system with integrated on-chip
      fluorescence detector has been microfabricated on a silicon substrate.
      Photodiodes in the silicon substrate measure fluorescence emitted from eluting
      molecules. The device incorporates an on-chip thin-film interference filter that
      prevents excitation light from inhibiting the fluorescence detection. A
      transparent AZO conducting ground plane is also used to prevent the high electric
      fields used for the separation from interfering with the photodiode response.
      Separations of DNA restriction fragments have been performed in these devices
      with femtogram detection limits using SYBR Green I intercalating dye.

PMID- 11321320
TI  - Concentration and separation of proteins in microfluidic channels on the basis of
      transverse IEF.
AB  - The use of microfluidic channels formed by two electrodes made of gold or
      palladium to perform transverse isoelectric focusing (IEF) is presented as a
      means for continuous concentration and fractionation of proteins. The
      microchannels were 40 mm long with an electrode gap of 1.27 mm and a depth of
      0.354 mm. The properties of pH gradients formed as a result of the electrolysis
      of water were influenced by variation of parameters such as the initial pH, ionic
      strength, and flow rate. Transverse IEF in pressure-driven flow is demonstrated
      using bovine serum albumin in a single ampholyte buffer as well as in multiple
      component buffers. Experimental results of protein focusing compare well to
      predictions of a mathematical model. Optimal conditions for efficient continuous
      fractionation of a protein mixture are summarized and discussed.

PMID- 11321321
TI  - Phenyl-modified reversed-phase liquid chromatography coupled to atmospheric
      pressure chemical ionization mass spectrometry: a universal method for the
      analysis of partially oxidized aromatic hydrocarbons.
AB  - A new liquid chromatographic method for the efficient separation of aromatic
      compounds having a wide range of sizes, molecular structures, and polarities has
      been developed. Based on a phenyl-modified silica reversed stationary phase and a
      methanol-water solvent gradient, it allows the separation of mono- and polycyclic
      aromatic hydrocarbons (PAHs) having up to five condensed aromatic rings and
      partially oxidized derivatives within a single chromatographic run of 40-min
      duration. The applicability of the method is demonstrated using 81 reference
      substances (PAHs, phenols, quinones, acids, lactones, esters, etc.) and real
      samples of environmental, medical, and technical relevance (ozonized PAHs, lake
      water, human urine, diesel exhaust condensates). The retention times of the
      investigated aromatics exhibit a regular increase with molecular mass and a
      systematic decrease with increasing number and polarity of functional groups. In
      case of intramolecular hydrogen bonding, a positive shift of retention time
      provides additional structural information. The combination of chromatographic
      retention time with the molecular mass and structural information from mass
      spectrometric detection allows the tentative identification of unknown aromatic
      analytes at trace levels, even without specific reference substances. With
      atmospheric pressure chemical ionization (APCI), low detection limits and highly
      informative fragmentation patterns can be obtained by in-source collision-induced
      fragmentation in a single-quadrupole LC-APCI-MS system as applied in this study,
      and multidimensional MS experiments are expected to further enhance the potential
      of the presented method.

PMID- 11321322
TI  - Limitations to the use of solid-phase microextraction for quantitation of
      mixtures of volatile organic sulfur compounds.
AB  - A study of the range of volatile organic sulfur compounds produced by brassica
      plants has highlighted limitations to the use of Carboxen/PDMS fibers for their
      analysis by solid-phase microextraction (SPME). These fibers are sometimes
      advocated for the analysis of sulfur gases, but a quantitative comparison of
      analytical data derived by SPME and by direct gas sampling of standard mixtures
      of volatile low molecular weight sulfur compounds at 0.01-10 mg/L has identified
      potential errors associated with their use. Higher molecular compounds displace
      lower molecular weight compounds as a consequence of competition for active sites
      on the fiber, and the relative proportions of the components adsorbed onto the
      fiber depend on their ratio in the headspace. As their relative concentrations
      change from sample to sample, the varying interactions result in irregular
      analytical responses, reflected in erratic calibration curves. Standards
      containing single components are not valid; only a standard containing all
      components found in the sample to be analyzed, and at the same relative
      concentrations, is appropriate. In practice, this may preclude the use of the
      fibers for quantitative analysis of multicomponent mixtures.

PMID- 11321323
TI  - Interdisciplinary research.

PMID- 11321324
TI  - Single molecule imaging sheds light on chromatography.

PMID- 11321325
TI  - "Matchsticks" for MALDI.

PMID- 11321326
TI  - Gradients from a microfluidic "Christmas tree".

PMID- 11321327
TI  - Chips to clear out crime backlog.

PMID- 11321328
TI  - ISAS regroups. Institute of Spectrochemistry and Applied Spectroscopy.

PMID- 11321329
TI  - Do pacts pay?

PMID- 11321330
TI  - New bioengineering institute at the NIH.

PMID- 11321331
TI  - New millenium new attitude?

PMID- 11321332
TI  - Chromatographic immunoassays.

PMID- 11321333
TI  - Imaging spectrometry from nature's own atomic lenses.

PMID- 11321334
TI  - NMR spectroscopy: past and present.

PMID- 11321335
TI  - Quartz crystal microbalances.

PMID- 11321336
TI  - Telomerase activity levels for evaluating the surgical margin in breast
      conserving surgery.
AB  - To evaluate the efficiency of measuring telomerase activity levels in clinical
      diagnosis, we performed a semiquantitative analysis of telomerase activity in
      breast tumors and compared the results with the histological findings. Breast
      tissue adjacent to areas of cancer were also serially resected and checked for
      telomerase activity. The amount of telomerase activity in the breast cancers
      ranged widely, from 0.36 to 1180 units/microg, with 31 of the 34 (91.2%) showing
      a value above 1.0unit/microg. None of the normal breast tissues including
      mastopathy, and only 4 (23.5%) of 17 benign breast masses had values above
      1.0unit/microg. Telomerase activity was detectable in serial sections of adjacent
      tissues as far as 10mm from the macroscopic tumor margin with histologically
      detectable cancer cells. Furthermore, telomerase activity was detectable in the
      scrape specimens obtained from the stump of the surgical margins for breast
      conserving surgery, and this activity was in accordance with the histological
      findings. These findings show that conducting a semiquantitative assay of
      telomerase activity is useful for evaluating the surgical margin in breast
      conserving surgery.

PMID- 11321337
TI  - Intrathoracic transposition of a pectoralis major and pectoralis minor muscle
      flap for empyema in patients previously subjected to posterolateral thoracotomy.
AB  - The latissimus dorsi muscle flap cannot be used to eliminate an empyema cavity in
      patients who have previously undergone posterolateral thoracotomy, because of the
      division of this muscle. Moreover, thoracoplasty alone cannot sufficiently
      eliminate an empyema cavity that includes the thoracic apex, where space remains
      between the clavicle and the first rib. Therefore, we constructed a flap from the
      pectoralis major (P.Ma) and pectoralis minor (P.Mi) muscles to eliminate empyema
      cavities in five patients who had undergone lobectomy (n = 3) or pneumonectomy (n
      = 2) via posterolateral thoracotomy from 3 months to 40 years previously. All
      five patients had bronchopleural fistulae, and because of the previous upper
      lobectomy or pneumonectomy, they had large empyema cavities including the
      thoracic apex. Open-drainage thoracotomy was performed due to severe infection,
      and intrathoracic transposition of the P.Ma and P.Mi muscle flap with
      simultaneous thoracoplasty was carried out 7-124 weeks (mean 38 weeks) later. The
      P.Ma and P.Mi muscle flap easily reached the apex space with sufficient
      obliteration of the empyema cavity. All of the patients remained free of empyema
      12-85 months after thoracic closure. The P.Ma and P.Mi muscle flap is useful for
      eliminating empyema cavities including the thoracic apex in patients who have
      previously undergone a posterolateral thoracotomy.

PMID- 11321338
TI  - Postoperative fecoflowmetric analysis in patients with anorectal malformation.
AB  - Because conventional methods of evaluating anorectal function do not necessarily
      provide good correlations between investigative results and symptoms in patients
      who have undergone surgery for an anorectal malformation (ARM), we recently
      introduced feco-flowmetry (FFM) to simulate natural anorectal evacuation. The
      purpose of this study was to embody significant parameters to elucidate the
      dynamics of anorectal activity on FFM. The parameters of FFM were compared with
      those of manometry and Kelly's clinical score (KCS) in 24 patients who underwent
      surgery for an ARM. There were three fecoflow patterns, namely, block (B) type,
      segmental (S) type, and flat (F) type. The B-type or S-type patterns were seen in
      patients classified as "clinically good." There were close relationships between
      the fecoflow pattern and both the operative procedure and the KCS (P = 0.01 and
      0.001, respectively). Maximum fecal stream flow rate (Fmax) precisely reflected
      the tolerance rate of intended normal saline solution in the colorectum (TR), the
      evacuative rate (ER), and KCS. Fmax > 45 ml/s or TR > 70% or ER > 50% was
      statistically regarded as the borderline of fecal continence. Thus, the fecoflow
      pattern might reflect the motor activity of the pelvic floor muscle. FFM provided
      quantiative and qualitative evaluations concerning anorectal motor activity in
      patients who had undergone surgery for an ARM.

PMID- 11321339
TI  - The importance of peripheral blood leukocytes and macrophage infiltration on
      bronchial wall wound healing in rats treated preoperatively with anticancer
      agents.
AB  - Preoperative chemotherapy is commonly used for small cell lung cancer or advanced
      non-small cell lung cancer. This study was conducted to investigate the effects
      of preoperative antineoplastic agents on the postoperative would healing of
      bronchial anastomoses in a rat model. Cisplatin (CDDP), doxorubicin (ADM), or
      cyclophosphamide (CPA) was administered either 3 days preoperatively (experiment
      1) or 7 days preoperatively (experiment 2). Wound healing was assessed on
      postoperative days (POD) 3, 5, and 7 after anastomosis of the bronchus, by
      examining the bursting strength and hydroxyproline tissue content. In experiment
      1, significant impairment of wound healing was seen on POD 3 in the CPA-treated
      rats, but no significant changes were seen in the other groups. Severe leukopenia
      and marked reduction of macrophage infiltration into the wound were also observed
      in the CPA-treated rats. The impairment of wound healing coincided with the time
      of leukopenia and reduced macrophage infiltration into the wounds. In experiment
      2, induction chemotherapy did not impair wound healing. Our experimental results
      suggest that preoperative chemotherapy producing mild leukopenia, or when
      followed by a sufficient interval to allow for the recovery of myelosuppression,
      did not impair wound healing of the bronchial anastomoses. The findings of this
      study also showed that the depletion of macrophages at the anastomotic site is
      one of the most important causes of impaired wound healing.

PMID- 11321340
TI  - Mixed medullary-papillary carcinoma of the thyroid with lymph node metastases:
      report of a case.
AB  - We report herein the case of a 77-year-old woman found to have mixed medullary
      papillary carcinoma in the right thyroid with lymph node metastases 30 years
      after a left thyroidectomy. The preoperative values of serum calcitonin and
      carcinoembryonic antigen (CEA) were high, and fine-needle aspiration biopsy
      revealed class V, which led us to suspect papillary carcinoma. A right
      thyroidectomy with dissection of the right neck lymph nodes was performed.
      Histopathological examination of the tumor specimens revealed gradual borders
      between medullary carcinoma and papillary carcinoma with positive
      immunohistochemical staining to calcitonin, chromogranin A, CEA, and
      thyroglobulin. The serum levels of calcitonin and CEA decreased to normal after
      the operation. The point mutation of the RET proto-oncogene was found to be
      negative by a DNA analysis of the peripheral leukocytes. This cancer seemed not
      to be associated with multiple endocrine neoplasia type 2 syndrome. The presence
      of both medullary and papillary components in the thyroid with lymph node
      metastases is rare and may suggest that the tumor had arisen from a common stem
      cell.

PMID- 11321341
TI  - Bochodalek hernia in a young adult: report of a case.
AB  - A Bochodalek hernia is rarely seen in adults. An 18-year-old man was referred to
      our institute with the chief complaint of a sudden onset of left subcostal pain,
      nausea, and vomiting. A radiograph and a computed tomographic scan of the chest
      revealed a Bochodalek hernia. Emergency surgery was thus performed. The herniated
      organs were put back into the peritoneal cavity and the hernial hilum was closed.
      The postoperative course was uneventful. A routine chest radiograph 1 month
      before had shown a slight elevation of the left hemidiaphragm and further
      examination using computed tomography suggested a Bochodalek hernia, but he had
      merely been followed up since there were no symptoms. As soon as a diagnosis is
      made, specific repairs should be carried out even if no symptoms are present, to
      prevent such complications as strangulation or perforation.

PMID- 11321342
TI  - Surgical treatment of cardiac echinococcosis: report of eight cases.
AB  - Cardiac involvement of hydatid disease is uncommon, and establishing a diagnosis
      is difficult because the presenting symptoms are variable. Between 1985 and 1997,
      eight patients ranging in age from 8 to 56 years underwent surgical excision of
      cardiac hydatid cysts, located in the interventricular septum in two, the right
      atrium in one, and the intrapericardium in five. There was one hospital death due
      to septic shock, but the other seven patients recovered uneventfully.

PMID- 11321343
TI  - Contained rupture of an abdominal aortic aneurysm presenting as obstructive
      jaundice: report of a case.
AB  - Chronic rupture of an abdominal aortic aneurysm (AAA) is a rare occurrence, the
      presentation of which is unusual, often mimicking other conditions such as
      femoral neuropathy or radicular compression syndrome. We report herein the case
      of an 87-year-old woman found to have a contained rupture of an AAA after
      presenting with back pain and obstructive jaundice. A computed tomography (CT)
      scan revealed the contained rupture of the aneurysm with a large hematoma
      compressing the common bile duct. Surgical repair of the aortic aneurysm was
      successfully performed and the patient remains well.

PMID- 11321344
TI  - Primary subclavian venous thrombosis which developed after sleeping with the arm
      in an outstretched position: report of a case.
AB  - Primary subclavian venous thrombosis is more rare than secondary thrombosis. This
      type of thrombosis is called "effort thrombosis" or Paget-Schroetter syndrome,
      and develops after a strenuous effort of the superior limb. A day after a 55-year
      old man got drunk and slept in the left lateral position in combination with an
      abducted and elevated position of the left superior limb, he became aware of
      swelling and an oppressive feeling in his left superior limb and was admitted 9
      days later. Thrombus of the left axillary-subclavian vein was confirmed by
      venography, and thrombolytic therapy with urokinase was performed immediately.
      The left arm symptoms improved for the most part. Venography after the therapy
      revealed thrombolysis at the site of the axillary vein, while the subclavian vein
      enhanced the collateral vessel pathway. The patient was discharged on the seventh
      hospital day, and anticoagulant therapy with oral warfarin sodium has since been
      continued. This is considered to be a rare case of subclavian venous thrombosis
      caused by sleeping in an abnormal position with the arm outstretched.

PMID- 11321345
TI  - An obstructed venous aneurysm presenting as an abdominal mass: report of a case.
AB  - We report herein the case of a 32-year-old woman found to have a venous aneurysm
      originating from the ovarian vein. The patient presented with a 9-cm abdominal
      tumor, and surgery was performed under the preoperative diagnosis of a mesenteric
      cyst. The tumor was easily ablated from the mesentery and resected with the right
      ovarian artery and vein. Histologically, the wall of the cyst showed the
      structure of a vein, and the diagnosis of a venous aneurysm was made. This
      disease is difficult to diagnose preoperatively when a patient presents with no
      symptoms other than a palpable mass, or when the lumen is obstructed by thrombus.
      This report serves to demonstrate that a venous aneurysm should be considered in
      the differential diagnosis of an asymptomatic abdominal mass.

PMID- 11321346
TI  - Gastric cancer with Virchow's and multiple lung metastases showing a remarkable
      response to preoperative chemotherapy: report of a case.
AB  - We report herein a rare case with advanced gastric cancer combined with group 4
      lymph node and lung metastases that responded remarkably to neoadjuvant
      chemotherapy. A 65-year-old man was found to have a well-differentiated type 3
      gastric cancer that invaded the duodenum locally and was accompanied with
      Virchow's, para-aortic lymph nodes, and multiple lung metastases based on
      physical, endoscopic, and radiological examinations. In addition, his
      carbohydrate antigen (CA) 19-9 was elevated to 3965U/ml, and CA72-4 to 46U/ml.
      Prior to surgery, he was treated with 5-fluorouracil (5-FU; 500mg/body per day)
      and low-dose cisplatinum (CDDP; 10mg/body per day) as neoadjuvant chemotherapy
      for 6 weeks. As a result, a partial response was obtained in all lesions, and
      CA19-9 and CA72-4 decreased to 463U/ml and 9.4U/ml, respectively. Four weeks
      after the completion of neoadjuvant chemotherapy, a distal gastrectomy was
      performed, and a histopathological examination of the resected specimen showed a
      grade 2 response to chemotherapy. Immunohistochemically, the thymidylate synthase
      expression level was very low in the tumor tissues, which might account for the
      good response to the combination chemotherapy with 5-FU and CDDP observed in the
      present case.

PMID- 11321347
TI  - Gastrointestinal stromal tumor of the stomach: report of a case.
AB  - We report herein the case of a 70-year-old woman found to have a gastrointestinal
      stromal tumor (GIST) of the stomach. Preoperative X-ray and endoscopic
      examination revealed a hemispheric submucosal tumor with central depression in
      the anterior wall of the gastric fornix. The tumor, which was 3 cm in diameter,
      was resected by a laparoscopy-assisted procedure. Histologic examination revealed
      that it was composed of spindle-shaped cells with elongated nuclei, and few
      mitoses. Most of the tumor cells showed immunoreactivity for vimentin and CD34,
      but not for alpha-smooth muscle actin, desmin, or S-100 protein. The PCNA index
      was 40.5%. Thus, the GIST did not show differentiation toward smooth muscle or
      neural cells. A gastrectomy was not performed because the small size of the
      tumor, and the paucity of the mitoses indicated that it was benign. Nevertheless,
      careful and long-term follow-up is needed to monitor for signs of possible local
      recurrence or distant metastases.

PMID- 11321349
TI  - Antegrade jejunojejunal intussusception after Roux-en-Y esophagojejunostomy as an
      unusual cause of postoperative intestinal obstruction: report of a case.
AB  - Postoperative intestinal obstruction in adults is rarely caused by
      intussusception. A case of antegrade jejunojejunal intussusception that occurred
      after Roux-en-Y esophagojejunostomy is described, followed by a discussion of the
      literature on this unusual entity.

PMID- 11321348
TI  - A spontaneously ruptured gastric stromal tumor presenting as generalized
      peritonitis: report of a case.
AB  - Among the diverse clinical presentations of gastrointestinal stromal tumor
      (GIST), spontaneous rupture with peritonitis is extremely rare. We report herein
      the unusual case of a 75-year-old man found to have a spontaneously ruptured
      gastric stromal tumor after presenting with generalized peritonitis. The patient
      was brought to the emergency department of our hospital by ambulance, with
      generalized severe abdominal pain. On examination, his abdomen was extensively
      distended with generalized severe rebound tenderness. Abdominal computed
      tomography scan showed a giant mass arising from the anterior gastric wall with
      an irregular internal low-density area and a small amount of ascites. An
      emergency laparotomy revealed a ruptured gastric tumor with dissemination of its
      necrotic tissue throughout the peritoneal cavity. The tumor was excised together
      with normal gastric tissue around its base. The tumor, which was 15 x 11 x 4.4cm
      in size, had a coarse laceration over its well-capsulated smooth serosal surface
      with massive necrosis and clotted blood inside. Immunohistochemical examination
      revealed positive reactivity to C-kit protein, which was consistent with the
      newly introduced diagnostic criteria of GIST. The patient had an uneventful
      postoperative course and remains well.

PMID- 11321350
TI  - Small bowel perforation caused by metastasis from an extra-abdominal malignancy:
      report of three cases.
AB  - Small bowel perforation is rarely caused by metastasis from an extra-abdominal
      malignancy. This report describes three cases of small bowel perforation that
      occurred secondary to a metastatic tumor. The first case involved a 72-year-old
      man with malignant lymphoma of the larynx that had been treated with chemo- and
      radiation therapy; the second involved a 70-year-old man with rhabdomyosarcoma of
      the mediastinum that had been treated with radiation therapy; and the third
      involved a 41-year-old man with lung carcinoma that had been treated with surgery
      10 months prior to perforation. Each patient presented with acute abdominal pain,
      had X-ray findings of free air in the abdomen, and underwent limited emergency
      surgery. Wedge resection and closure of the ileum was performed for the first
      patient and partial bowel resection with the creation of an intestinal stoma was
      performed for the second and third patients. In each case, the histologic
      findings of the resected specimens were consistent with the extra-abdominal
      primary tumors. Although the patients recovered sufficiently to begin eating and
      moving about, all three died of cancer or cancer-related complications within 45
      days of surgery. We conclude that surgeons should be aware of the poor prognosis
      of such patients and perform only the minimal surgery required.

PMID- 11321351
TI  - Pedicle myocutaneous flaps for reconstruction following total pelvic exenteration
      of intrapelvic recurrent rectal cancer: report of a case.
AB  - A vast metastatic tumor mass of recurrent rectal carcinoma in the intrapelvic
      organs is commonly considered unsuitable for total pelvic exenteration (TPE);
      first, because it is unlikely that it would improve the prognosis and health
      related quality of life of the patient, and second, because of the difficulties
      involved in this surgical technique. However, by using a plastic surgery
      technique involving reconstruction by filling the pelvic dead space with pedicle
      myocutaneous flaps (PMF), primary wound closure and extensive resection of the
      perineum can be achieved, whereby postoperative metastasis may be prevented. We
      report herein the case of a 71-year-old man found to have local recurrence in the
      perineum with extensive invasion of the soft tissue as well as adjacent organs,
      20 months after abdominal perineal resection for rectal carcinoma. TPE with
      extensive resection of the perineal soft tissue was performed, followed by
      perineal reconstruction and packing of the pelvic dead space with PMF, mainly
      constructed from the gracilis and sartorius muscles of both femurs. His
      postoperative course was uneventful and he has remained free of local recurrence
      and symptomatic perineal complaints for 1 year. In this report, we examine the
      effectiveness of using the gracilis muscle for PMF in intrapelvic and perineal
      reconstruction after TPE.

PMID- 11321352
TI  - Intrahepatic pseudoaneurysm after surgical hemostasis for a delayed  hemorrhage
      due to blunt liver injury: report of a case.
AB  - We report herein a case of delayed hemorrhage occurring after blunt hepatic
      trauma which was further complicated by an intrahepatic pseudoaneurysm. The
      delayed hemorrhage with free rupture occurred 2 weeks after the injury and the
      pseudoaneurysm developed 8 weeks after surgical hemostatic intervention for the
      delayed hemorrhage. The pseudoaneurysm was successfully treated by transcatheter
      arterial embolization. This rare case is reported to demonstrate the possibility
      of delayed catastrophic complications occurring after blunt liver injury and to
      point out the necessity of continued surveillance until the liver has completely
      healed.

PMID- 11321353
TI  - Ectopic vascularization of the right kidney by a contralateral origin of the main
      renal artery from the left common iliac artery: report of a case.
AB  - In daily practice, an atypical renal blood supply is a rare finding. An ectopic
      origin of the right main renal artery from the contralateral common iliac artery
      was observed when angiography was performed to diagnose irregularities in
      perfusion of the lower extremities and to determine the necessity for vascular
      surgical intervention in a 66-year-old man. Conservative treatment was successful
      in this patient, who suffered from intermittent claudication because of an
      obstruction of the superficial femoral arteries. The diagnostic approach with
      angiography is considered to be essential for revealing such anomalies.
      Conventional vascular surgical reconstruction would have threatened the perfusion
      of the right kidney in this case.

PMID- 11321354
TI  - Successful surgical treatment of renal cell carcinoma in a transplanted kidney
      from a cadaveric donor: report of a case.
AB  - Posttransplant renal cell carcinoma (RCC) usually arises in the native kidneys of
      renal transplant recipients rather than in the transplanted kidney. This report
      describes a case of RCC that developed in the transplanted cadaveric kidney in a
      37-year-old male recipient 9 months after transplantation. An en bloc radical
      transplant nephrectomy was performed, and he has subsequently remained stable on
      hemodialysis for 3 years without any sign of recurrence.

PMID- 11321355
TI  - Small incisional esophagectomy with endoscopic assistance: evaluation of a new
      technique.
AB  - Laparoscopic surgery now can be performed safely and efficiently for various
      types of cancer; however, reconstruction of the gastric tube may be technically
      demanding. We attempted to make a breakthrough by designing and employing a new
      technique for performing a small incisional operation with endoscopic assistance.
      A midline incision, 10cm in length, was made in the upper abdomen. Some
      procedures were performed through the incision under direct vision, while other
      procedures required in the lateral extremes of the abdominal cavity, that are
      inaccessible by direct vision, were performed by laparoscopic-assisted surgery.
      Similarly, intrathoracic procedures were essentially performed through a
      minithoracotomy, 10-15cm in length, made without dissection of the dorsal
      latissmus or anterior serratus muscles. The postoperative courses of 20
      consecutive patients who underwent this procedure were generally uneventful, and
      significant improvements in terms of intensive care and analgesic requirements
      were observed.

PMID- 11321356
TI  - Circulating E-selectin levels in chronic hepatitis C patients with normal or
      elevated transaminase before and after alpha-interferon treatment.
AB  - E-selectin, an adhesion molecule of the selectin family, is involved in leukocyte
      adhesion to the endothelium and in the cellular immunological reactions.
      Expression of this molecule, in fact, is physiologically absent, but it becomes
      evident on sinusoidal lining cells during inflammatory liver disease. The aim of
      this study was to evaluate the behavior of E-selectin in chronic hepatitis C (CH
      C) patients with persistently normal transaminase in comparison to patients with
      CH-C and elevated transaminase, and its changes during alpha-interferon therapy.
      Immunohistochemical localization of E-selectin was also performed on liver tissue
      specimens of both groups. Fifty-eight subjects were divided into 3 groups: group
      A included 18 patients with CH-C and persistently normal transaminase; group B 20
      patients with CH-C and persistently elevated transaminase levels and group C
      included 20 healthy subjects, representing the control group. The first two
      groups were treated with r-IFN alpha at a dose of 6 MU 3 times a week for 3
      months and followed-up with 3 MU 3 times a week for another 3 months. Serum
      baseline values of E-selectin in groups A and B were significantly higher than
      those in group C (P < 0.04), but there was no difference between groups A and B.
      Furthermore, there was a trend toward higher E-selectin values as histological
      severity increased (r = 0.69; P < 0.0001). Post-treatment E-selectin serum values
      showed a moderate decrease in both groups, but only among responder patients;
      while E-selectin levels were unchanged in non responders. Immunohistochemical
      localization showed no staining for E-selectin in normal liver specimens, while
      there was a quite similar staining for E-selectin in the two groups of patients.
      In conclusion, this study shows that serum E-selectin levels in patients with CH
      C and persistently normal transaminase are higher than in controls and they are
      associated with severity of liver disease. Liver of these patients express E
      selectin molecules, suggesting an activation of the immune system almost
      identical to that of patients with CH-C and elevated transaminase. In both groups
      only responder patients showed a moderate decrease below baseline serum values.

PMID- 11321357
TI  - Glucocorticoids and TGF-beta1 synergize in augmenting fibroblast mediated
      contraction of collagen gels.
AB  - TGF-beta plays a central role in the initiation and progression of pulmonary
      fibrosis. Glucocorticoids are frequently used to treat fibrotic diseases, but
      beneficial effects are often modest. Both TGF-beta and glucocorticoids have been
      reported to increase fibroblast contraction of native collagen gels, a model of
      fibrotic tissue remodeling. Therefore, we sought to determine how glucocorticoids
      interact with TGF-beta in this system. In this study, human fetal lung
      fibroblasts (HFL-1) were pretreated with or without TGF-beta for 72 h before they
      were cast into type I collagen gels. Various concentrations of glucocorticoids
      (budesonide or hydrocortisone) were added at the time of casting. Gel size was
      then monitored at different times after gel release. The surrounding media were
      collected for the assay of prostaglandin E2 (PGE2) and the cell lysates were
      analyzed for cyclooxygenase (COX) expression by immunoblot. Glucocorticoids alone
      significantly enhanced fibroblast-mediated contraction of collagen gels (P <
      0.01) and dose-dependently inhibited PGE2 release by HFL-1 fibroblasts. TGF-beta
      significantly augmented gel contraction but also induced a 30% increase in PGE2
      release and increased the expression of COX-1. Glucocorticoids inhibited TGF
      beta1 induced-PGE2 release, and enhanced TGF-beta augmented gel contraction
      without significantly affecting TGF-beta augmented COX-1 expression.
      Indomethacin, a COX inhibitor, increased TGF-beta augmented gel contraction but
      had no further effect when added together with glucocorticoids. Thus,
      glucocorticoids can synergize with TGF-beta in augmenting fibroblast mediated
      collagen gel contraction through the inhibition of PGE2 production. Such
      interactions between glucocorticoids and TGF-beta may account, in part, for the
      lack of response of fibrotic diseases to glucocorticoids.

PMID- 11321358
TI  - Acute effects of the anti-inflammatory cyclooxygenase-2 selective inhibitor,
      flosulide, on renal plasma flow and glomerular filtration rate in rats.
AB  - Nephrotoxicity of nonsteroidal anti-inflammatory drugs is associated with other
      risk factors (volume-depletion) and may be secondary to functional changes
      mediated by the inhibition of renal cyclooxygenases. Acute anti-inflammatory
      doses of flosulide and indomethacin were determined on carrageenan paw edema and
      its effects on renal plasma flow (RPF) and glomerular filtration rate (GFR) were
      studied in normovolemic and hypovolemic rats. In normovolemic rats, flosulide
      increased RPF and GFR (25 mg/kg) and indomethacin (5-10 mg/kg) was without
      effect. Volume-depleted rats were obtained by oral furosemide (32 mg/kg), urinary
      eicosanoids were determined. After furosemide, plasma volume, RPF and GFR and
      PGE2 decreased. Treatment of hypovolemic rats with flosulide (5-25 mg/kg) or
      indomethacin 10 mg/kg reduced RPF and GFR. Flosulide at 5 mg/kg reduced 6-keto
      PGF1alpha whereas at 25 mg/kg and after indomethacin at 10 mg/kg a fall in 6-keto
      PGF1alpha and TXB2 appeared. Our data suggest that acute COX-2 selective
      inhibition may alter renal function.

PMID- 11321359
TI  - Blood polymorphonuclear leukocyte activation in atherosclerosis: effects of
      aspirin.
AB  - The aim of the study was to demonstrate an activation of polymorpho-nuclear
      leukocytes (PMNs) in chronic progressive atherosclerosis (ATH). A group of
      patients with ATH, and a group of ATH patients under aspirin (ASA) therapy were
      compared with control persons without atherosclerotic alterations (healthy
      controls). Each group comprised 15 male age-matched subjects. The following
      inflammatory parameters related to PMN activities were measured: the
      polymorphonuclear leukocyte (PMN) blood count; blood PMN migration and reactive
      oxygen species release in vitro; the blood levels of PMN elastase,
      malondialdehyde, antibodies to oxidized LDL and soluble ICAM-1. In ATH patients,
      the PMN blood counts and the share of blood PMNs migrating upon platelet
      activating factor and leukotriene B4 stimulation were significnatly above the
      values of the healthy controls, while the other parameters were not significantly
      altered. ASA treatment attenuated the inflammatory response and reduced the
      differences between ATH and the healthy controls. It can be concluded that, in
      patients with chronic progressive atherosclerosis, PMNs are involved in the
      inflammatory process underlying the disease.

PMID- 11321360
TI  - Evaluation of signal transduction pathways in chemoattractant-induced human
      monocyte chemotaxis.
AB  - The intracellular signaling pathways involved in human monocyte chemotaxis toward
      a variety of chemoattractant molecules were evaluated using selected
      pharmacological agents. Neither phosphatidylinositol-3-kinase (P13K) or
      extracellular signal-regulated kinase (ERK) activity were required for monocyte
      migration toward monocyte chemoattractant protein-1 (MCP-1), RANTES (Regulated on
      Activation, Normal T cell Expressed and Secreted), macrophage inflammatory
      protein-1alpha (MIP-1alpha) or formyl-Met-Leu-Phe (fMLP), since pretreatment with
      wortmannin or LY294002, or with PD098059, had no effect on the chemotactic
      response. Addition of forskolin and IBMX significantly attenuated chemotaxis to
      each of these chemoattractants and was reversed by co-treatment with Rp-cAMP, a
      competitive inhibitor of cAMP-dependent protein kinase A. Incubation with the
      protein kinase C (PKC) inhibitor GF109203X-HCl (GF109) did not affect monocyte
      migration, but pretreatment of monocytes with PMA significantly impaired the
      response to each of these chemotactic agents. Inhibition by PMA was reversed by
      co-treatment with GF109, implying that heterologous PKC activation is capable of
      desensitizing chemokine and fMLP-induced monocyte chemotaxis. These results help
      to define the signalling pathways involved in human monocyte chemotaxis and
      suggest pharmacological approaches to evaluating the cross-desensitization of
      chemoattractant-induced leukocyte migration.

PMID- 11321361
TI  - TGF-beta1 null mutation leads to CD154 upregulated expression in affected
      tissues.
AB  - The TGF-beta1(-/-) mouse is a murine model for systemic autoimmune disease. The
      aim of this study is to elucidate the immunological mechanism that leads to
      multifocal tissue inflammation and autoantibody production in TGF-beta1(-/-)
      mice. Heart, lung, liver, and salivary gland from TGF-beta1(-/-) were assessed
      for CD154 expression by RT-PCR and immunohistochemistry. Compared to wild-type
      littermates, CD154 expression was elevated in all tissues studied. Furthermore,
      IL-12 mRNA was expressed in the salivary gland and heart of TGF-beta1(-/-) mice
      and not in wild-type littermates. This suggests that the CD154 pathway is
      activated in these tissues. This shows that TGF-beta1 regulates CD154 expression
      leading to spontaneous IL-12 production and autoimmunity.

PMID- 11321362
TI  - Downregulation of lipopolysaccharide-induced intercellular adhesion molecule-1
      expression via EP2/EP4 receptors by prostaglandin E2 in human fibroblasts.
AB  - In the present study, the effect of prostaglandin E2 (PGE2) on intercellular
      adhesion molecule-1 (ICAM-1) expression in human gingival fibroblasts (HGF)
      stimulated with lipopolysaccharides (LPS) was investigated. LPS were isolated
      from periodontopathic bacteria, Actinobacillus actinomycetemcomitans (A.
      actinomycetemcomitans) and Porphyromonas gingivalis (P. gingivalis), by the
      phenol-water method and Escherichia coli (E. coli) LPS was used as a control.
      PGE2 significantly inhibited A. actinomycetemcomitans-, P. gingivalis- and E.
      coli-LPS-induced ICAM-1 expression. Next, of four PGE2 receptor subtypes (EP1,
      EP2, EP3 and EP4), we examined which subtype(s) was involved in inhibition of LPS
      elicited ICAM-1 expression by PGE2. Eleven-deoxy-PGE1, a selective EP2/EP4
      agonist, and butaprost, a selective EP2 agonist, attenuated A.
      actinomycetemcomitans-, P. gingivalis- and E. coli-LPS-elicited ICAM-1
      expression, although butaprost was less potent than PGE2 and 11-deoxy-PGE1.
      Sulprostone, an EP1/EP3 agonist, and ONO-AP-324, an EP3 agonist, was inert to the
      LPS-elicited ICAM-1 expression. Furthermore, dibutyryl cAMP, a cAMP analogue, and
      forskolin, an adenylate cyclase activator, downregulated A. actinomycetemcomitans
      , P. gingivalis- and E. coli-LPS-elicited ICAM-1 expression in HGF. Our data
      suggest that PGE2 downregulates A. actinomycetemcomitans- and P. gingivalis-LPS
      induced ICAM-1 expression in HGF, via EP2/EP4 receptors by cAMP-dependent
      signaling pathways. The cAMP-elevating agents such as EP2/EP4 receptor activators
      may serve to control inflammatory and immune responses in periodontal disease.

PMID- 11321363
TI  - Effects of C5a and FMLP on interleukin-8 production and proliferation of human
      umbilical vein endothelial cells.
AB  - Interleukin-8 (IL-8), C5a and N-formyl-methionyl-leucyl-phenylalanine (fMLP) are
      chemotactic peptides with predominant effects on leukocytes during inflammation.
      With emphasis on C5a we studied the regulation of the production of IL-8 by human
      umbilical vein endothelial cells (HUVEC) in vitro. Primary HUVEC cultures were
      incubated with IL-1alpha, TNFalpha, C5a and fMLP for 24 h and 48 h prior to
      measurement of IL-8 in supernatants of the cells by an enzyme immunoassay.
      Whereas IL-1alpha and TNFalpha significantly increased the levels of IL-8, C5a
      decreased the IL-8 production after 48 h. In addition, the ability of IL-1alpha,
      TNFalpha, C5a, fMLP and IL-8 to induce cell proliferation was compared by means
      of a 3H-thymidine incorporation assay. In contrast with IL-1alpha and TNFalpha,
      both C5a and fMLP increased cell proliferation of HUVEC. This increase occurred
      with increasing concentrations of C5a contrary to IL-8, which showed increased
      cell proliferation at low, but not high IL-8 concentrations.

PMID- 11321364
TI  - Differential effects of thalidomide on angiogenesis and tumor growth in mice.
AB  - Thalidomide, clinically used as an antiinflammatory and antitumoral drug,
      inhibited sponge-induced angiogenesis when administered systemically (100 mg/kg(
      1)) in mice. However, it failed to inhibit solid Ehrlich tumor in the same mouse
      strain. We have used functional, biochemical and histological parameters to
      assess neovascularization and fibrovascular tissue infiltration of the mice
      sponge granuloma. The neovascularization growth as detected by development of
      blood flow and hemoglobin content extracted from the implants showed that
      thalidomide inhibited fibrovascular tissue formation by 40%. The functional and
      biochemical parameters correlated well with the histological study. Thalidomide
      had no inhibitory effect in the development of Ehrlich tumor. The detection of
      this selective action using the same animal strain bearing two different
      processes, supports the hypothesis that rather than species specificity,
      thalidomide is tissue specific. This approach may be used to identify the
      specificity of other therapeutic agents against distinct angiogenesis-dependent
      diseases.

PMID- 11321365
TI  - Plasma levels of procalcitonin and interleukin-6 in acute myocardial infarction.
AB  - Estimation of cardiac morbidity in patients after major surgery is a difficult
      problem. In addition, infectious complications seriously decrease potential
      beneficial outcome after cardiovascular surgery. The present study assessed the
      use of a newer marker of the inflammatory response, procalcitonin, in the field
      of myocardial infarction, in conjunction with measurements of interleukin-6.
      Forty-four consecutive cases with acute myocardial infarction were included in
      the study 4+/-1.3 h after the onset of symptoms. Plasma levels of procalcitonin
      and interleukin-6 were obtained at admission, and after 3, 6, 12, 18, 24 and 48
      h, using commercially available test kits. The range of levels of interleukin-6
      and procalcitonin was about normal at admission. Interleukin-6 levels increased
      significantly following myocardial infarction, whereas procalcitonin were
      essentially unchanged, i.e. remained close to the normal level threshold of 0.5
      ng/ml; only minor variability occurred with a mean peak level of procalcitonin of
      1+/-0.4 ng/ml. Data demonstrate that, in contrast to the acute phase reactant
      interleukin-6, plasma levels procalcitonin are not significantly elevated during
      uncomplicated acute myocardial infarction. This observation may support the role
      of procalcitonin measurements in the differential diagnosis of infectious and
      cardiovascular complications after major surgery.

PMID- 11321367
TI  - Chiasma formation in Arabidopsis thaliana accession Wassileskija and in two
      meiotic mutants.
AB  - Meiotic chiasmata were analysed in metaphase I pollen mother cells (PMCs) of wild
      type Arabidopsis thaliana and in two meiotic mutants. Fluorescence in situ
      hybridisation (FISH) with 45S rDNA and 5S rDNA as probes was used to identify the
      five chromosome pairs. A wild-type chiasma frequency of 9.24 per cell was found,
      consistent with estimated genetic recombination values. Individual bivalent
      chiasma frequencies varied according to chromosome size; chromosome 1 had the
      highest mean chiasma frequency (2.14) while the short acrocentric chromosomes had
      the lowest frequencies (1.54 and 1.56). FISH analysis was extended to two meiotic
      mutants (asy1 and dsy1) having low residual bivalent and chiasma frequencies.
      Mutant dsy1 gave no indication of chromosome preference for residual bivalent
      formation; instead it showed a general reduction in bivalent and chiasma
      frequencies. In asy1, the longest chromosome (1) had the lowest bivalent
      frequency and chiasma frequency while the short acrocentric chromosome 2 had the
      highest frequencies. This chromosome pair may be preferentially involved in
      synapsis and chiasma formation because of their association with the nucleolus.
      However, other factors may be operating since the other acrocentric chromosome
      (4), with similar size and structure to chromosome 2, did not share these chiasma
      properties.

PMID- 11321366
TI  - Comparative chromosome and mitochondrial DNA analyses and phylogenetic
      relationships within common voles (Microtus, Arvicolidae).
AB  - The four species of common voles within the genus Microtus--M. kirgisorum, M.
      transcaspicus, M. arvalis, and M. rossiaemeridionalis--are so closely related
      that neither morphological features nor paleontological evidence allow
      clarification of their phylogeny. Analysis of vole karyotypes and mitochondrial
      DNA sequences, therefore, is essential for determining their phylogenetic
      relationships. A comparison of high resolution GTG-banding patterns allows us to
      ascertain the similarity between the karyotypes of these species, revealing that
      they are composed of rearrangements of the same chromosomal elements. Based on
      this analysis, we propose possible routes of chromosomal divergence involved in
      speciation within this group of voles and construct a phylogenetic tree of their
      karyotypes. We suggest that two different karyotypic variants existed during the
      course of vole evolution--one resulting in M. rossiaemeridionalis and M.
      transcaspicus, the other, M. kirgisorum and M. arvalis. As an alternative
      approach FITCH and KITSCH computer programs were used to construct a phylogenetic
      tree of vole molecular evolution based on a pairwise comparison of mitochondrial
      cytochrome b sequences and the divergence time of the species was determined. The
      correlation between the trees constructed using karyologic and molecular
      approaches is discussed in the context of other available data.

PMID- 11321368
TI  - Chromosomal distribution of reverse transcriptase-containing retroelements in two
      Triticeae species.
AB  - A large portion of plant and particularly cereal genomes consist of repetitive
      DNA families, many of which are likely to be or to have evolved from
      retroelements. Molecular evidence suggests that repeated DNA sequences, although
      perhaps originating as innocuous or 'selfish' elements, can have dramatic effects
      on genome organization and function. Knowledge of chromosomal distribution of
      retroelements is important for understanding plant chromosome
      structure/functional organization, and could shed light on the dynamics of
      retroelements and their role in the evolutionary process. In the present study we
      aim to find a possible correlation between physical location of the regions with
      species-specific sequences and the distribution of conserved RT domains of the
      Ty1-copia, Ty3-gypsy and LINE groups of retroelements on the chromosomes of two
      diploid species that belong to the different branches of the tribe Triticeae,
      namely Aegilops speltoides Tausch (2n=2x=14) and Hordeum spontaneum L (2n=2x=14).
      All three groups of retroelements were found in large quantities in the genomes
      of the tested species. They are cluster-distributed, and the important role of
      these elements in the formation of terminal heterochromatin is shown. We found
      that there was a predominance of Ty1-copia and LINE elements in the chromosome
      regions with preferential content of species-specific sequences.

PMID- 11321369
TI  - Chromosome healing by addition of telomeric repeats in wheat occurs during the
      first mitotic divisions of the sporophyte and is a gradual process.
AB  - Alien gametocidal chromosomes cause extensive chromosome breakage prior to S
      phase in the first mitotic division of gametophytes lacking the alien chromosome.
      The broken chromosomes may be healed either by addition of telomeric repeats in
      the gametophyte or undergo fusions to form dicentric or translocation
      chromosomes. We show that dicentric chromosomes undergo breakage fusion-bridge
      (BFB) cycles in the first few mitotic divisions of the sporophyte, are partially
      healed before the germ line differentiation regimen, and are healed completely in
      the ensuing gametophytic stage. The gametocidal factor on chromosome 4Mg of
      Aegilops geniculata was used to induce dicentrics involving the satellite
      chromosomes1B and 6B of wheat, Triticum aestivum. The dicentrics 1BS x 1BL-2AL x
      2AS and 6BS x 6BL-4BL x 4BS initiated BFB cycles that ceased 2 to 4 weeks after
      seed germination. At the end of the BFB cycles, we observed deficient 1B and 6B
      chromosomes with breakpoints in proximal regions of the 1BL and 6BL arms. The
      process of chromosome healing was analyzed in root tip meristems, at meiotic
      metaphase I, and in the derived progenies by fluorescence in-situ hybridization
      analysis using a telomeric probe pAtT4. The results show that chromosome healing
      in wheat occurs during very early mitotic divisions in the sporophyte by de-novo
      addition of telomeric repeats and is a gradual process. Broken chromosome ends
      have to pass through several cell divisions in the sporophyte to acquire the full
      telomeric repeat length.

PMID- 11321370
TI  - Transcripts of the MHM region on the chicken Z chromosome accumulate as non
      coding RNA in the nucleus of female cells adjacent to the DMRT1 locus.
AB  - The male hypermethylated (MHM) region, located near the middle of the short arm
      of the Z chromosome of chickens, consists of approximately 210 tandem repeats of
      a BamHI 2.2-kb sequence unit. Cytosines of the CpG dinucleotides of this region
      are extensively methylated on the two Z chromosomes in the male but much less
      methylated on the single Z chromosome in the female. The state of methylation of
      the MHM region is established after fertilization by about the 1-day embryonic
      stage. The MHM region is transcribed only in the female from the particular
      strand into heterogeneous, high molecular-mass, non-coding RNA, which is
      accumulated at the site of transcription, adjacent to the DMRT1 locus, in the
      nucleus. The transcriptional silence of the MHM region in the male is most likely
      caused by the CpG methylation, since treatment of the male embryonic fibroblasts
      with 5-azacytidine results in hypo-methylation and active transcription of this
      region. In ZZW triploid chickens, MHM regions are hypomethylated and transcribed
      on the two Z chromosomes, whereas MHM regions are hypermethylated and
      transcriptionally inactive on the three Z chromosomes in ZZZ triploid chickens,
      suggesting a possible role of the W chromosome on the state of the MHM region.

PMID- 11321371
TI  - FISH with locus-specific probes on stretched chromosomes: a useful tool for
      genome organization studies.

PMID- 11321372
TI  - The structural maintenance of chromosomes (SMC) family of proteins in mammals.
AB  - Structural maintenance of chromosomes (SMC) family proteins play critical roles
      in chromosome structural changes. SMC proteins are known to be involved in two
      major chromosome structural organization events required for mitotic segregation
      of chromosomes: mitotic chromosome condensation and sister chromatid cohesion. In
      eukaryotes, two separate sets of SMC heterodimers form the cores of two distinct
      multiprotein complexes termed 'condensin' and 'cohesin', each specialized for
      condensation or cohesion, respectively. It is clear that both condensin and
      cohesin are conserved in mammals, including humans. The mammalian complexes
      demonstrate dynamic changes in intracellular distribution in a cell cycle
      dependent manner. At any point in the cell cycle, the intracellular localization
      of the majority of mammalian cohesin and condensin appears to be complementary.
      Cohesin is associated with chromatin in interphase, while condensin is largely
      cytoplasmic. Similarly, in mitosis, cohesin is mostly excluded from chromosomes
      while condensin is distinctly bound to them. Cell cycle-dependent targeting of
      the two complexes appears to play a major role in regulating their cell cycle
      specific activities, and how this redistribution is controlled is an area of
      active research. Finally, there is evidence that SMC proteins may be involved in
      DNA recombination and repair. This review focuses on what we have learned about
      SMC family proteins in humans and other mammalian species in comparison to those
      in lower eukaryotes. The authors present their own views with regard to some of
      the major outstanding questions surrounding the nature and functions of the SMC
      family of proteins.

PMID- 11321373
TI  - Reciprocal chromosome painting between a New World primate, the woolly monkey,
      and humans.
AB  - We employed fluorescence-activated chromosome sorting (FACS) to construct
      chromosome paint sets for the woolly monkey (Lagothrix lagotricha) and then FISH
      to reciprocally paint human and woolly monkey metaphases. Reciprocal chromosome
      painting between humans and the woolly monkey allowed us to assign subchromosomal
      homologies between these species. The reciprocal painting data between humans and
      the woolly monkey also allow a better interpretation of the chromosomal
      difference between humans and platyrrhines, and refine hypotheses about the
      genomic rearrangements that gave origin to the genome of New World monkeys.
      Paints of woolly monkey chromosomes were used to paint human metaphases and forty
      five clear signals were detected. Paints specific to each human chromosome were
      used to paint woolly monkey metaphases. The 23 human paints gave 39 clear signals
      on the woolly monkey karyotype. The woolly monkey chromosomes painted by human
      paints produced 7 associations of segments homologous to human chromosomes or
      human chromosome segments: 2/16, 3/21, 4/15, 5/7, 8/18, 10/16 and 14/15. A
      derived translocation between segments homologous to human chromosomes 4 and 15
      is a synapomorphic marker linking all Atelines. These species may also be linked
      by fragmentation of homologs to human 1, 4, and 15.

PMID- 11321374
TI  - Just plain uggly.

PMID- 11321376
TI  - The future of pediatric research looks bright.

PMID- 11321375
TI  - Maintenance of certification in the USA: a program for assessment of continuing
      competence.

PMID- 11321377
TI  - A multicenter trial of 6-mercaptopurine and prednisone in children with newly
      diagnosed Crohn disease.

PMID- 11321378
TI  - Enteropathogenic Escherichia coli strain RDEC-1 produces a novel electrogenic
      factor active on rabbit ileum in vitro.
AB  - BACKGROUND: Attaching and effacing Escherichia coli demonstrate marked species
      specificity in inducing diarrhea, although its mechanism remains largely unclear.
      The purpose of this study was to investigate the existence of a soluble, species
      specific factor that induces diarrhea in an in vitro model. METHODS: Stripped
      rabbit ileum was mounted in Ussing chambers, and changes in potential difference
      and short-circuit current were monitored after the addition of bacterial culture
      supernatant. RESULTS: The culture supernatant from rabbit-specific strain RDEC-1,
      but not from human-specific enteropathogenic Escherichia coli strain E2348/69,
      induced an increase in potential difference and short-circuit current in rabbit
      ileum mounted in Ussing chambers. This electrical signal was related to chloride
      ion secretion, was absent in colonic tissue, and was retained in the 30 to 100
      KDa fraction of the supernatant. Preliminary experiments failed to show an
      involvement of calcium or cyclic nucleotides as intracellular messengers. RDEC-1
      cured of a 42-MDa plasmid lost the enterotoxicity whereas conjugation of the
      plasmid into the negative E. coli recipient HB101 resulted in the expression of
      toxicity. CONCLUSIONS: The authors describe a novel, species-specific factor that
      helps to explain RDEC-1 diarrhea, which may be relevant to the pathogenesis of
      enteropathogenic Escherichia coli infection.

PMID- 11321379
TI  - An infant formula free of glycomacropeptide prevents hyperthreoninemia in formula
      fed preterm infants.
AB  - BACKGROUND: Hyperthreoninemia is a well-known phenomenon in infants fed a whey
      protein-predominant formula. Sweet whey is commonly used for the production of
      these whey-predominant infant milk formulas. Sweet whey contains not only whey
      proteins but also the threonine-rich glycomacropeptide (GMP). In the current
      study, an experimental formula based on acid whey without GMP and a formula based
      on sweet whey with GMP (threonine content 17.2% higher than in the experimental
      formula) but otherwise with identical composition were tested with particular
      respect to threonine metabolism. METHODS: Fourteen preterm infants appropriate
      for gestational age were enrolled in this randomized cross-over study. After a
      feeding period of at least 7 days, the nutrition of each infant was switched to
      the other formula for the second feeding period. At the end of each feeding
      period, the concentrations of creatinine and amino acids in the plasma and in the
      urine were measured. RESULTS: In the plasma, the threonine concentration was
      significantly lower in the group fed the experimental GMP-free formula than in
      the group fed the sweet whey formula (P < 0.001). Renal excretion of all
      essential amino acids was generally very low and less than 2% of the intake,
      indicating that the kidneys had no marked homeostatic function with respect to
      plasma amino acid. The plasma concentrations of the threonine metabolites glycine
      and serine, and that of urea were not influenced by diet. CONCLUSION: Feeding a
      whey protein-predominant bovine milk produced from acid whey protein reduces
      significantly the hyperthreoninemia commonly found in formula-fed preterm
      infants. Thus, acid whey formulas should be recommended for feeding preterm
      infants.

PMID- 11321380
TI  - Autoimmune hepatitis as a late complication of liver transplantation.
AB  - BACKGROUND: The development of de novo autoimmune hepatitis as a long-term
      complication after liver transplantation has been recently reported. The authors
      describe five liver allograft recipients who developed chronic hepatitis
      associated with autoimmune features. METHODS: Five of 155 liver transplant
      recipients at risk (2.5%) developed this particular form of graft dysfunction.
      The authors review the clinical records, liver histology, therapy, and outcome of
      these five patients. RESULTS: Patients included two boys and three girls. Median
      age at transplantation was 3.5 years (range, 0.5-14 years), median age at
      presentation was 9 years (range, 2-17 years), and median interval after
      transplantation was 5.1 years (range, 1.5-9 years). Indications for liver
      transplant included biliary atresia in four patients and primary sclerosing
      cholangitis in one patient. At the time of presentation, all patients were
      receiving cyclosporine as their primary immunosuppressive agent. Only one patient
      had a history of rejection, which had resolved. All patients presented with
      increased transaminase levels, and one had a mildly elevated conjugated bilirubin
      level. Only one patient had constitutional complaints. Acute and chronic
      rejection, viral hepatitis, vascular insufficiency, and biliary tract obstruction
      were excluded. Antinuclear antibody levels were elevated in four patients (titer
      range, 1:160-1:640), one of whom also had positive antismooth muscle antibody
      (titer 1:80) results. The fifth patient had an elevated serum total protein
      level. Histologic analysis of liver biopsy samples from the five patients showed
      findings consistent with chronic autoimmune hepatitis. All patients were treated
      with standard therapy for autoimmune hepatitis, which included daily steroids and
      azathioprine. Cyclosporine doses were reduced in three patients and eliminated in
      two. All patients responded with normalization (n = 2) or improvement (n = 3) of
      liver transaminases within the first 3 months of therapy. Histologic analysis of
      the 3-month follow-up liver biopsy was normal (n = 2) or showed improvement in
      inflammation (n = 2). Two patients developed acute allograft rejection within 6
      to 12 months after discontinuation or reduction in cyclosporine. CONCLUSIONS:
      Autoimmune hepatitis occurs after liver transplantation in patients without a
      previous history of autoimmune hepatitis. The risk of developing autoimmune
      hepatitis appears to be greater in children after liver transplantation than in
      the general pediatric population. Standard therapy for autoimmune hepatitis is
      effective.

PMID- 11321381
TI  - Effect of preterm formula with and without long-chain polyunsaturated fatty acids
      on the urinary excretion of F2-isoprostanes and 8-epi-prostaglandin F2alpha.
AB  - BACKGROUND: The objective of this study was to evaluate the effect of
      conventional and long-chain polyunsaturated fatty acids (LCP)-enriched preterm
      formula on the endogenous formation of F2-isoprostanes and 8-epi-prostaglandin
      (PG) F2alpha as possible markers of lipid peroxidation in preterm infants during
      their first weeks of life. METHODS: In a prospective, randomized, double-blind
      study, infants received either formula enriched with LCP (n = 8), standard
      preterm formula (n = 7), or (expressed) breast milk (n = 8). Urine was sampled at
      study entry and after the study period of 3 weeks. The formation of F2
      isoprostanes and 8-epi-PGF2alpha was evaluated by measuring the urinary excretion
      by gas chromatography-mass spectrometry. RESULTS: No differences in the urinary
      excretion of F2-isoprostanes and 8-epi-PGF2alpha were observed at the end of the
      study period. CONCLUSIONS: This result suggests that supplementation of a preterm
      formula with LCP for a period of 3 weeks does not stimulate lipid peroxidation in
      preterm infants.

PMID- 11321383
TI  - Omeprazole maintenance therapy for gastroesophageal reflux disease after failure
      of fundoplication.
AB  - BACKGROUND: Recurrence of gastroesophageal reflux (GER) in children after failed
      fundoplication poses a therapeutic challenge. The authors report the experience
      with long-term omeprazole for children with severe GER after failed
      fundoplication. METHODS: The authors reviewed the charts of all children who were
      treated with omeprazole for GER subsequent to failed fundoplication from 1990 to
      1999. All underwent endoscopic and clinical assessment of the treatment at
      baseline, at 3-5 months, at 6-9 months, and annually. RESULTS: Eighteen children
      presented with GER, after a total of 27 fundoplications. Ten had corrected
      esophageal atresia, 6 had neurologica impairment, and 2 had hiatal hernia. The
      mean age of presentation of children with recurrence of GER was 7.8 years, and
      symptoms of GER occurred 4.9 years (range, 0.6-13) after last fundoplication.
      Fifteen patients had a mean follow-up of 4.4 years for omeprazole. Ten patients
      had grade III/IV esophagitis and 5 had grade II esophagitis at presentation after
      fundoplication. Marked improvement was noted in symptoms of GER and severity of
      esophagitis while taking omeprazole. Remission of esophagitis was maintained
      while the patient was taking omeprazole and none had further surgery. There was
      no recurrence of peptic strictures in eight of nine children on omeprazole, after
      initial esophageal dilatations. Except for benign gastric polyps in three
      patients, no clinical adverse effects were observed. CONCLUSIONS: Omeprazole is
      an effective long-term drug for gastroesophageal reflux disease after failed
      fundoplication in children. Omeprazole was well-tolerated by all children and
      should be tried before subsequent surgical intervention.

PMID- 11321382
TI  - Could local anesthesia while breast-feeding be harmful to infants?
AB  - BACKGROUND: Few studies have been carried out on the levels and possible toxicity
      of local anesthetics in breast milk after parenteral administration. The purpose
      of this study is to determine the amount of lidocaine and its metabolite
      monoethyl-glycinexylidide (MEGX) in breast milk after local anesthesia during
      dental procedures. METHODS: The study population consisted of seven nursing
      mothers (age, 23-39 years) who received 3.6 to 7.2 mL 2% lidocaine without
      adrenaline. Blood and milk concentrations of lidocaine and its metabolite MEGX
      were assayed using high-performance liquid chromatography. The milk-to-plasma
      ratio and the possible daily doses in infants for both lidocaine and MEGX were
      calculated. RESULTS: The lidocaine concentration in maternal plasma 2 hours after
      injection was 347.6 +/- 221.8 microg/L, the lidocaine concentration in maternal
      milk ranged from 120.5 +/- 54.1 microg/L (3 hours after injection) to 58.3 +/-
      22.8 microg/L (6 hours after injection), the MEGX concentration in maternal
      plasma 2 hours after injection was 58.9 +/- 30.3 microg/L, and the MEGX
      concentration in maternal milk ranged from 97.5 +/- 39.6 microg/L (3 hours after
      injection) to 52.7 +/- 23.8 microg/L (6 hours after injection). According to
      these data and considering an intake of 90 mL breast milk every 3 hours, the
      daily infant dosages of lidocaine and MEGX were 73.41 +/- 38.94 microg/L/day and
      66.1 +/- 28.5 microg/L/day respectively. CONCLUSIONS: This study suggests that
      even if a nursing mother undergoes dental treatment with local anesthesia using
      lidocaine without adrenaline, she can safely continue breastfeeding.

PMID- 11321384
TI  - Helicobacter pylori and Meckel's diverticula.
AB  - BACKGROUND: Helicobacter pylori is known to infect only gastric mucosa and is
      strongly associated with gastroduodenal ulceration. The authors studied whether
      H. pylori colonizes the gastric mucosa of Meckel's diverticula, and determined
      its relationship to "gastritis" and bleeding. METHODS: A 10-year retrospective
      review identified 45 children with Meckel's diverticulum. Hematoxylin-eosin and
      Diff-Quik stains were used to assess the presence and severity of gastritis, and
      to highlight organisms in the resected diverticula. Cases with organisms were
      then studied with antibodies specific for H. pylori using immunoperoxidase
      methods. RESULTS: Twenty-eight children, 7 months to 12.6 years of age, had lower
      gastrointestinal hemorrhage caused by Meckel's diverticulum and had positive
      radionuclide scans. All had acid-secreting mucosa in their diverticula, and
      ulceration. "Chronic gastritis" and eosinophilia were constant findings; "acute
      gastritis" was present in four patients. Twenty specimens exhibited lymphoid
      follicles in the gastric mucosa. Seventeen patients with Meckel's diverticula
      (age range, 1 month-14.7 years) who presented with acute abdominal pain
      associated with intussusception were used for comparison. Acid-secreting gastric
      mucosa was seen in four patients. H. pylori was identified in only one of the 45
      patients; this patient had ulceration and moderate "acute gastritis."
      CONCLUSIONS: H. pylori does not colonize a substantial number of children who
      have ulcerated and bleeding Meckel's diverticulum in the presence of acid
      secreting mucosa. Although H. pylori is a notable cause of ulceration, the
      authors confirm that ulceration is possible in its absence, and alternative
      mechanisms of ulceration are important. The presence of lymphoid follicles in
      Meckel's diverticula, unlike gastric biopsies, is not associated with H. pylori.

PMID- 11321385
TI  - Residual intestinal disease after milk allergy in infancy.
AB  - BACKGROUND: The subsidence of cow's milk allergy (CMA) has been a subject of
      controversy. In this study the authors examined whether children with this
      condition in infancy developed full tolerance or whether they continue to have
      vague gastrointestinal (GI) symptoms relating to the consumption of milk or dairy
      products and/or signs of mucosal lesion in the GI tract. METHODS: The authors
      reexamined 56 10-year-old subjects who manifested CMA before 1 year of age, and
      compared the results with a group of 204 randomly selected age-matched school
      children. Fifty-three and 90 subjects respectively attended a reexamination and
      were evaluated for growth, lactose tolerance, and immunoglobulin A (IgA)- and IgG
      class antibodies to whole cow's milk. The subjects reporting milk-related GI
      symptoms were encouraged to do a 4-week blind elimination-challenge test with 1
      week of low-lactose milk flour. Sixteen of the 25 children were able to complete
      the trial. RESULTS: Approximately half the study subjects (45%) reported milk
      related GI symptoms, whereas the respective figure among the control subjects was
      10%. Three of six study subjects and seven of 10 control subjects, although
      completing the challenge, responded with intestinal symptoms. The growth of the
      former CMA subjects was retarded compared with the control subjects, and the
      difference in height was most striking in those subjects still reporting milk
      related GI symptoms. However, all subjects had normal hemoglobin and whole-blood
      folic acid levels. The CMA subjects had significantly (P = 0.014) lower
      concentrations of milk antibodies compared with the control subjects. Lactose
      malabsorption, defined as high counts in a hydrogen breath test and related
      clinical symptoms, was found in eight CMA subjects (14%) and six control subjects
      (3%). CONCLUSIONS: In a certain proportion of subjects with CMA in infancy, GI
      intolerance seems to persist even after small-dose tolerance has been achieved.
      The intestinal symptoms and the increased prevalence of lactose intolerance may
      be caused by a disturbance of the surface epithelial cells--a state to which the
      authors refer as residual intestinal disease.

PMID- 11321386
TI  - Survival of rotavirus antibody activity derived from bovine colostrum after
      passage through the human gastrointestinal tract.
AB  - BACKGROUND: Rotavirus is a major cause of infectious diarrhea in infants and
      young children. Several studies have shown that hyperimmune bovine colostrum,
      derived from cows immunized with rotavirus, can prevent rotavirus diarrhea when
      given passively. The objective of this study was to determine whether colostral
      antibody activity survived transit through the gut by measuring the level of
      rotavirus antibody activity in the feces. METHODS: Hyperimmune colostrum
      containing different levels of rotavirus antibody was administered to 105
      children attending nine Adelaide childcare centres. Subjects were asked to drink
      100 ml of whole milk supplemented with colostrum 3 times a day, for a period of 6
      days. Stool samples were collected from the subjects before, during, and after
      consumption of the study product. Rotavirus activity was determined using a novel
      virus reduction enzyme-linked immunosorbent assay (ELISA) and a virus
      neutralization assay. RESULTS: Rotavirus antibody activity was detected in 521
      (86%) of 602 fecal specimens obtained during the study using the virus reduction
      ELISA. The antibody activity was detected as early as 8 hours after ingestion of
      hyperimmune colostrum and up to 72 hours after consumption had ceased. There was
      a strong relation (r = 0.81) between the titer of rotavirus antibody administered
      to subjects and the level of antibody activity detected in the feces.
      CONCLUSIONS: The results show that antirotavirus activity survived passage
      through the gut. Therefore, passive immunotherapy may be used to prevent or treat
      infectious diseases that affect the entire length of the gastrointestinal tract.

PMID- 11321387
TI  - Successful immune response to a recombinant hepatitis B vaccine in children after
      liver transplantation.
AB  - BACKGROUND: Patients who undergo liver transplantation require multifaceted
      general care, and vaccination has a fundamental role before and after
      transplantation. The purpose of this study was to provide a prospective
      evaluation of the immunogenicity of the recombinant vaccine (RV) against
      Hepatitis B in pediatric patients with liver transplants (TxH) who for different
      reasons did not receive a pretransplantation vaccine. METHODS: From June 1996 to
      December 1999, 47 pediatric patients with liver transplants were vaccinated with
      RV. Patients older than 1 year of age, in stable condition, and 6 months post
      transplantation were included. The vaccination scheme was 0-1 and 6 months,
      intramuscular 10 microg in less than 30 kg body weight, and 20 microg in more
      than 30 kg body weight. The nonresponder patients were vaccinated with a booster
      dose and a double dose 1 to 6 months after the last dose. Responders to titer HBs
      Ab enzyme immunoassay (EIA) <10 UI/ml were defined as nonresponders, to titer
      between 10-100 UI/ml as responders, and to higher titer of 100 UI/ml as high
      responders. RESULTS: The following data were obtained from the 47 patients: mean
      +/- standard deviation (SD) age at vaccination was 10.76 +/- 5.96 years old and
      the mean +/- SD post-transplant time at the beginning of vaccination was 3.56 +/-
      2.19 years. Thirty-three of 47 patients (70%) responded to doses according to
      body weight, and 14 (30%) did not respond, necessitating a booster dose after
      which 7 responded (50%). The global seroconversion was 85%. There was not a
      significant responder cyclosporine concentration dosage (154 vs. 150 ng/ml)
      difference between responders and nonresponders. Sixty-six percent (8 of 12) of
      patients receiving a triple immunosuppressive scheme (cyclosporine, steroids, and
      Azathioprine) had a positive response, while 84% (16 of 19) receiving a double
      scheme (cyclosporine and steroids) and 100% (16 of 16) receiving monotherapy with
      cyclosporine had a positive response. By comparing a triple scheme with
      monotherapy, the Fisher exact test found a P < 0.01. Incidence of adverse effects
      (local pain) was 2.63%. CONCLUSION: Immunization with RV was well-tolerated with
      acceptable seroconversion and safety in recipients after liver transplantation,
      particularly in those undergoing cyclosporine monotherapy. The population studied
      showed better results than did other populations of immunosuppressed patients.

PMID- 11321388
TI  - Fecal calprotectin as a measure of disease activity in childhood inflammatory
      bowel disease.
AB  - BACKGROUND: Calprotectin is an abundant neutrophil protein that is extremely
      stable in feces. The aim of this study was to assess the effectiveness of fecal
      calprotectin as a noninvasive measure of disease activity in childhood
      inflammatory bowel disease (IBD) by comparison to a modified Lloyd-Still and
      Green score and laboratory inflammatory indices. METHODS: Spot fecal samples from
      37 children with IBD and 31 control children were sent by ordinary mail to the
      laboratory. Fecal calprotectin concentration was measured by an in-house enzyme
      linked immunosorbent assay (ELISA). A modified Lloyd-Still & Green score (mLSS)
      was calculated for each child with IBD within 10 days of obtaining the fecal
      sample. RESULTS: Compared with control values (median, range) (2.1, 0.5-6.3
      mg/L), fecal calprotectin was increased in 16 children with ulcerative colitis,
      (11.5, 0.6-272.5 mg/L, P < 0.001) and in 21 children with Crohn disease, (14.0,
      0.7-59.7 mg/L, P < 0.001). Twelve "moderately affected" children (mLSS of 35-65)
      had higher fecal calprotectin concentrations (22.2, 2.7-141.7 mg/L) than 25
      "mildly affected" children (mLSS > 65), (10.3, 0.6-272.5 mg/L, P = 0.002). For
      the total IBD group, fecal calprotectin concentration correlated negatively with
      the mLSS (r = -0.61, P < 0.001). It also correlated negatively with serum albumin
      concentration (r = -0.49, P = 0.002) and positively with erythrocyte
      sedimentation rate (r = 0.40, P = 0.01). CONCLUSIONS: Fecal calprotectin seems to
      reflect bowel inflammation in children with IBD. As a simple, safe, noninvasive
      test, it has the potential to reduce the number of invasive investigations
      performed in these children.

PMID- 11321389
TI  - Efficacy of long-term treatment with thalidomide in children and young adults
      with Crohn disease: preliminary results.
AB  - BACKGROUND: Several proinflammatory cytokines are involved in the pathogenesis of
      inflammatory bowel diseases. A significant role has been given to tumor necrosis
      factor alpha (TNF-alpha) as a guide proinflammatory cytokine. Thalidomide
      selectively reduces TNF-alpha production by inflammatory cells. The aim of the
      study was to assess the efficacy of thalidomide to induce and maintain remission
      in refractory Crohn disease. METHODS: The decision to administer thalidomide was
      made on the basis of patient intolerance or resistance to conventional medical
      treatment or as the last medical resort before surgical intervention. Only 5 of
      96 patients with inflammatory bowel disease satisfied these criteria. All five
      patients had Crohn disease (male: mean age, 17 years). Thalidomide was
      administered at night at a dose of 1.5-2 mg/kg/day. The Pediatric Crohn Disease
      Activity Index, modified Harvey-Bradshaw scores, and steroids reduction were used
      to assess clinical response. RESULTS: Disease activity decreased consistently in
      four patients with a reduction of mean Pediatric Crohn Disease Activity Index
      from 36,9 to 2,5 and the mean Harvey-Bradshaw from 8.5 to 0.75 after 3 months of
      treatment. Steroid treatment (mean dose, 35 mg/day before treatment) was tapered
      and then discontinued, in four patients, within 1-3 months. Four patients are in
      remission after 19-24 months of treatment. The fifth patient discontinued
      thalidomide after 1 week because of distal paresthesia. CONCLUSION: Thalidomide
      seems to be an effective and safe treatment in patients with refractory Crohn
      disease. This is the first report of long-term use of thalidomide in refractory
      Crohn disease in pediatric patients.

PMID- 11321390
TI  - Gastroesophageal endoscopic findings and gastrointestinal symptoms in preterm
      neonates with and without perinatal indomethacin exposure.
AB  - BACKGROUND: The aim of this study was to investigate whether perinatal
      indomethacin treatment has effects on the development of esophageal and gastric
      lesions in preterm infants and to evaluate other potential etiologic factors
      behind these lesions. METHODS: Sixty-nine infants were born at less than 33
      weeks' gestation. Forty-five of these infants underwent treatment with perinatal
      indomethacin (study group) and 24 did not (control group). All underwent upper
      gastrointestinal tract endoscopy and biopsy during the neonatal period. The
      correlation between gastrointestinal symptoms, abnormal endoscopic findings, and
      the factors correlating with the development of esophageal and gastric mucosal
      lesions was evaluated. RESULTS: Abnormal endoscopic findings were equally common
      in the study group (77.8%) and in controls (83.3%). There was no dependence
      between gastrointestinal symptoms and endoscopic findings because only 15 infants
      (21.7%) were symptomatic before endoscopy. The interval between endoscopy and the
      last perinatal indomethacin dose correlated significantly with abnormal
      esophageal findings and gastric mucosal lesions. Shorter duration of enteral
      feeding before endoscopy correlated with greater risk of abnormal esophageal
      findings. Older gestational age and need of ventilator treatment at the time of
      endoscopy remained the risk factors associated with abnormal gastric findings.
      CONCLUSIONS: Esophageal and gastric lesions diagnosed by endoscopy correlate
      poorly with the gastrointestinal symptoms of patients. Short duration of enteral
      feeding seems to be correlated with an increased risk of esophageal mucosal
      lesions, increasing gestational age and ventilator treatment with gastric mucosal
      lesions, and perinatal indomethacin with esophageal and gastric mucosal lesions
      in preterm infants. Ventilator-treated preterm infants not receiving enteral
      nutrition and patients with indomethacin exposure might benefit from ulcer
      prophylaxis.

PMID- 11321392
TI  - Crohn-like enteritis presenting as hypoglycemia in a patient with glycogen
      storage disease type 1b, treated with granulocyte colony-stimulating factor and
      splenectomy.

PMID- 11321391
TI  - The interrelationship of malnutrition and diarrhea in a periurban area outside
      Alexandria, Egypt.
AB  - BACKGROUND: In the developing world, children are often observed to have both
      diarrhea and malnutrition. This observation has led many researchers to speculate
      that diarrhea may produce malnutrition and that malnutrition may predispose to
      diarrhea. In this study, the interrelationship between diarrhea and malnutrition
      was investigated among 143 Egyptian children less than 3 years of age. METHODS:
      For 22 months, children were followed for diarrhea at twice weekly home visits
      and measured for nutritional status at approximately 3-month intervals.
      Nutritional measurements were converted to z-scores based on the National Center
      for Health Statistics/World Health Organization (NCHS/WHO) reference population.
      RESULTS: Three hundred fifty-eight diarrheal episodes were reported with only 1%
      of episodes lasting 14 days or more. Stunting, wasting, and low weight-for-age
      were found in 19%, 3%, and 7%, of these children, respectively. When testing
      whether malnutrition predisposes to diarrhea, a weight-for-age z-score of <-2
      standard deviations was associated with increased incidence of diarrhea (RR =
      1.7, P < 0.01) but not height-for-age or weight-for-height. Diarrhea itself was
      associated with a subsequent attack of diarrhea (RR = 2.1, P < 0.001). During
      short intervals of follow-up (approximately 3 months), an association was
      detected between diarrhea episodes and growth faltering for height-for-age z
      score (-0.16, P < 0.05). This association was reduced, however, when analyzed
      during 6-month intervals, if no diarrhea was reported in either the first or
      second half of this interval. CONCLUSIONS: In a population with moderate
      malnutrition, both low weight-for-age and diarrhea itself are associated with
      increased diarrhea risk. Diarrhea alone does not appear to contribute
      substantially to malnutrition when children have diarrhea-free time for catch-up
      growth.

PMID- 11321393
TI  - Achalasia in an adolescent with Fabry disease.

PMID- 11321394
TI  - Immature gastric teratoma of the lesser curvature in a male infant.

PMID- 11321395
TI  - Systemic absorption with complications during topical tacrolimus treatment for
      orofacial Crohn disease.

PMID- 11321396
TI  - Cerebral venous thrombosis as a complication of Crohn disease: a case report.

PMID- 11321397
TI  - Gastrojejunostomy button migration into the duodenal bulb mimicking
      ventriculoperitoneal shunt malfunction.

PMID- 11321398
TI  - Clinical quiz. Solitary rectal ulcer.

PMID- 11321399
TI  - Fundic gland polyposis with high-grade dysplasia in a child with attenuated
      familial adenomatous polyposis and familial gastric cancer.

PMID- 11321400
TI  - Lichenification and enlargement of hands and feet: a sign of progressive familial
      intrahepatic cholestasis with normal gamma-glutamyl-transpeptidase.

PMID- 11321401
TI  - Crohn disease in early childhood.

PMID- 11321402
TI  - Granulocyte colony stimulating factor for the treatment of interferon-induced
      neutropenia in patients with chronic hepatitis B.

PMID- 11321403
TI  - Choosing triple therapy for Helicobacter pylori in children: antimicrobial
      resistance testing of first gastric biopsy culture may predict outcome.

PMID- 11321404
TI  - Obesity in an 18-year-old boy with untreated celiac disease.

PMID- 11321405
TI  - Celiac disease screening: exploring the iceberg with salivary antigliadin
      antibodies.

PMID- 11321406
TI  - Decreased Na+/K+ pump activity in the erythrocytes of children with treated
      celiac disease.

PMID- 11321407
TI  - Topographic manometry: an evolving method for motility.

PMID- 11321408
TI  - The neurophysiology of emesis: lessons from basic science for understanding
      paediatric problems.

PMID- 11321409
TI  - Cyclic vomiting syndrome.

PMID- 11321410
TI  - Regurgitation & GERD.

PMID- 11321411
TI  - Medical and surgical therapies for GERD.

PMID- 11321412
TI  - Chronic intestinal pseudo-obstruction: the clinical perspective.

PMID- 11321413
TI  - Chronic intestinal pseudo-obstruction: the pathologist's perspective.

PMID- 11321414
TI  - Small intestinal transplantation: past, present, future.

PMID- 11321415
TI  - Emerging techniques in the evaluation of gastric motility and gastric afferent
      sensation.

PMID- 11321416
TI  - The physiology of gastrointestinal motility.

PMID- 11321417
TI  - Dyspepsia: functional or not?

PMID- 11321418
TI  - Irritable bowel syndrome: contrasts and comparisons between children and adults.

PMID- 11321419
TI  - Novel medications for the irritable bowel syndrome: motility and sensation.

PMID- 11321420
TI  - Controversies in the management of chronic constipation.

PMID- 11321421
TI  - Psychological management strategies for functional disorders.

PMID- 11321422
TI  - Diagnosis and treatment efficacy of functional non-retentive fecal soiling in
      childhood.

PMID- 11321423
TI  - Nutritional management of pediatric patients with chronic intestinal pseudo
      obstruction syndrome.

PMID- 11321424
TI  - Functional gastrointestinal disorders and the biopsychosocial model of practice.

PMID- 11321425
TI  - Inflammation, food allergy and motility.

PMID- 11321426
TI  - Direct in vivo visualization of glomerular microcirculation by intravital pencil
      lens-probe CCD videomicroscopy.
AB  - There have been developed several types of experimental techniques for evaluation
      of renal microcirculation. Although each methodology possesses excellent and
      unique characteristics, it requires substantial artificial manipulation that
      might alter the renal microvascular responsiveness. To circumvent such
      limitations of previous ex vivo or in vitro approaches to glomerular
      microcirculation, we have developed a pencil lens probe CCD intravital
      videomicroscopic system that allows us to evaluate both systemic hemodynamics and
      renal microcirculation. Furthermore, real time images of afferent and efferent
      arterioles as well as glomeruli can be continuously assessed, which would
      facilitate the functional characterization of these microvessels in vivo.
      Finally, the tapered nature of the CCD probe of this videomicroscopy may allow
      direct observation of the renal microvasculature in small animals. In conclusion,
      this novel technique is a valuable tool for unveiling the in vivo, in situ, and
      intact renal microvascular behavior, and may provide further approaches to the
      understanding of renal microcirculation.

PMID- 11321427
TI  - Dysfunction of microvascular endothelial cells induced by tumor necrosis factor
      (TNFalpha): cellular and molecular mechanism.
AB  - The dysfunction of rat pulmonary microvascular endothelial cells (RPMVEC) induced
      by tumor necrosis factor alpha (TNFalpha) was investigated in cell culture. The
      TNFalpha concentrations added into culture were 1000-5000 u/ml. The study was
      done at different steps as follows: (1) cell proliferation dynamic, (2)
      coagulation and anti-coagulation, (3) adhesive molecule, (4) nitric oxide (NO),
      (5) oncogens, and (6) apoptosis. It was concluded that attention should be paid
      to the metabolic disorder and dysfunction of RPMVEC induced by TNFalpha which can
      not be found easily according to the morphological changes. This might be the
      common pathway in the pathogenesis of some diseases related to TNFalpha.

PMID- 11321428
TI  - Dietary antioxidative potential in arteries.
AB  - Many researches show that traditional Indonesian diet is good for physical
      health. The present study examines the antioxidative, anti-inflammatory and
      antithrombotic potentials of aqueous extract of tempe (fermented soya-beans) and
      Curcuma domestica in an experimental photochemical thrombogenesis model using rat
      femoral artery. A total of 15 male Wistar rats weighing 250 g were used, and
      divided into three groups: control (group-1, n = 5), animals, treated orally with
      0.25 ml aqueous extracts of 50 g tempe (fermented soybean cake) once daily for 7
      consecutive days (group-2, n = 5) and animals treated orally with 0.25 ml aqueous
      extracts of 10 g roots of Curcuma domestica once daily for 5 consecutive days
      (group-3, n = 5). All animals were anesthetized, and Sn-pyrophosphate and Tc99m
      solutions were injected intravenously for in vivo red cell radioactive labeling.
      Femoral arterial occlusion was observed, using a gamma camera. Induction of
      femoral arterial thrombosis was effected following an endothelial injury by free
      radicals produced by green light-irradiated Rose Bengal (10 mg/kg). The results
      showed that in the control group arterial total flow occlusion was seen in 15 min
      of irradiation. The results of MDA absorbency was 0.3700 +/- 1.7 nmol/ml in
      control group-1, 0.0520 +/- 0.025 in group-2 (significant p < 0.05 in comparison
      to control group) and 0.2780 +/- 0.027 in group-3 (non-significant). Interleukin
      1alpha plasma level was 14.44 +/- 2.3 in control group-1, 8.93 +/- 2.4 in group-2
      (significant p < 0.05), and 6.21 +/- 2.5 in group-3 (significant p < 0.05).
      Plasma thromboxane B2 plasma level was 20.31 +/- 2.4 in control group-1, 14.32 +/
      2.2 in group-2 (significant p < 0.05), and 19.41 +/- 2.1 in group-3
      (significant). This study suggests the potential antioxidative, anti-inflammatory
      and antithrombotic effect that the dietary aqueous extracts has in rat femoral
      artery.

PMID- 11321429
TI  - Microvascular medicine in Asia.
AB  - The frontiers of microcirculatory research in the present world is reviewed in
      relation to the development of genomics and post-genomics.

PMID- 11321430
TI  - Asian traditional medicine: from molecular biology to organ circulation.
AB  - Asian tradition medicine (ATM), such as herbal medicine and acupuncture, has been
      widely used in the treatment of diseases, but the effects still remain unclear at
      the level of the microcirculation. Up to now, a variety of approaches have been
      made to comprehensively evaluate the significance of ATM. Microcirculatory
      studies of ATM are introduced with reference to the history of international
      workshops in Asia.

PMID- 11321431
TI  - Herbs of activating blood circulation to remove blood stasis.
AB  - Drugs with the efficacy of modifying rheological properties of blood, blood
      vessels and their interactions are denoted by "hemorheologicals". Drugs of anti
      hyperviscosemia, anti-coagulants, anti-platelet drugs, anti-thrombotics,
      vasodilators, endothelial cell protectors and anti-arthrosclerosis should be
      considered as hemorheologicals due to the actions in keeping blood fluidity and
      in maintaining normal vascular functions. The studies in hemorheology indicate
      that a tendency of hyperviscosity, hypercoagulation and being prone to thrombosis
      is prevalent in the elderly. Hemorheologicals are importance for and aging and
      life-threatening diseases. Blood stasis syndrome is a common pathological
      syndrome in the elderly. In traditional Chinese medicine, the treatment for the
      syndrome is by herbs which activates blood circulation to remove blood stasis.
      The herbs have the efficacy of improving hemorheological events. Therefore, the
      herbs are the source for developing hemorheologicals. Ligustrazine isolated from
      Chuangxiong is an example. It showed significant inhibition on shear induced
      platelet aggregation and on platelet intracellular calcium demonstrated by laser
      confocal microscope.

PMID- 11321432
TI  - The therapeutic effect of Ginkgo biloba extract in SHR rats and its possible
      mechanisms based on cerebral microvascular flow and vasomotion.
AB  - This paper aimed to investigate the therapeutic effect of an extract of Ginkgo
      biloba leaves (EGb 761) on hypertension and its possible mechanisms in the view
      of cerebral microcirculation. Twenty normotensive rats and 24 SHR rats were used.
      Surgical preparation was made to produce a cranial window for observation of the
      capillary network on the cerebral cortex. The intravital videomicroscopy equipped
      with digital image processing system and laser Doppler flowmeter were used for
      this study. The arterial blood pressure, red cell velocity (V), microvacular
      diameter (D), number of open capillaries (OCN), circulating endothelial cells
      (CEC) in blood, relative blood flow (Flow) and frequency (Fc), amplitude (AMP) of
      vasomotion were measured. The obtained data were compared between EGb-treated
      rats that received per os 100 mg/kg/d for 9 days and placebo control rats.
      Untreated SHR rats showed very severe dysfunction in the microcirculation with
      high blood pressure (213 +/- 16.7 mmHg). The blood pressure decreased
      significantly to 153 +/- 20 mmHg in EGb-treated SHRs group, compared with those
      of untreated rats (p < 0.01). Both normotensive and hypertensive rats increased
      the blood flow velocity and LDF flow after EGb-treatment. The vasomotion
      property, the CEC and OCN changed greatly in EGb-treated SHR rats, but no
      significant difference was observed in normotensive rats. It was suggested that
      EGb 761 had therapeutic effect on SHR rats by increasing blood perfusion,
      regulating vasomotion function, opening efficiently capillaries and releasing the
      peripheral resistance. The injured vascular endothelium of SHR rats was also
      partly reversed by EGb-treatment. It was concluded that EGb 761 could be used to
      regulate hypertension and to protect the cerebral microcirculatory function.

PMID- 11321433
TI  - Effects of Ginkgo biloba extract on somatosensory evoked potential, nitric oxide
      levels in serum and brain tissue in rats with cerebral vasospasm after
      subarachnoid hemorrhage.
AB  - This study aimed to investigate the protective effects of Ginkgo biloba extract
      on cerebral vasospasm and neural damage following subarachnoid hemorrhage (SAH)
      in rats. It was found that the regional cerebral blood flow decreased immediately
      and persistently after SAH in SAH rats. The latency of somatosensory evoked
      potential delayed progressively. The nitric oxide levels in serum and brain
      tissue decreased and increased, respectively, after SAH. Ginkgo biloba extract
      effectively antagonized the changes of above parameters. It was concluded that
      somatosensory evoked potential is useful for the judgement of cerebral ischemic
      damage during cerebral vasospasm after SAH. Decrease in serum nitric oxide and
      increase in brain tissue nitric oxide are important factors leading to cerebral
      vasospasm and neural damage, respectively, after SAH. Ginkgo biloba extract
      relieves cerebral vasospasm and cerebral ischemic damage by reversing the
      pathological alteration of nitric oxide.

PMID- 11321434
TI  - Tetramethylpyrazine inhibits phytohemagglutinin-induced upregulation of ICAM-1
      and LFA-1 mediated leukocyte adhesion.
AB  - The aim of this work was to study the effects of tetramethylpyrazine (TMP) on the
      interaction between lymphocyte function-associated antigen-1 (LFA-1) and
      intercellular adhesive molecule-1 (ICAM-1) by micropipette technique. A pair of
      cells, i.e., a human lymphocyte or a S KW-3 cell (human T cell leukemia), LFA-1
      was expressed on which cellular surfaces, and a RBC coupled with ICAM-1, were the
      carriers for LFA-1 and ICAM-1. The adhesion probabilities of this pair of cells
      were mediated by specific interactions between ICAM-1 and LFA-1.
      Phytohemagglutinin (PHA) stimulation resulted in the significant increase in the
      adhesion probability compared to the resting lymphocyte. TMP treatment can
      inhibit such increase and even make the adhesion probability lower than the
      resting state. While the LFA-1 expression has not changed significantly with PHA
      stimulation or with TMP treatment, which indicated that TMP inhibiting effects
      was realized by a possible conformation change.

PMID- 11321435
TI  - Macro- and microcirculatory effects of tetramethylpyrazine and extract of
      Charthamus tinctorius L. in rabbit mesentery.
AB  - Effects of tetramethylpyrazine (TMP) and that of extracts of Charthamus
      tinctorius L. (CTL) on the macro- and microcirculation in rabbit mesentery were
      studied. The intestinal arterial blood flow (Qa) was measured using an
      electromagnetic flowmeter, together with the arterial blood pressure (Pa). The
      inner diameter and red cell velocity in single arteriole in the mesentery were
      measured by a video-image technique and a dual-slit photometric method,
      respectively. Using the measured diameter and red cell velocity, the arteriolar
      blood flow (Qm) was calculated. Both the Qa and Qm decreased when Pa was
      decreased after the intravenous administration of TMP, CTL, Nicardipine,
      Phentolamine and acetylcholine (Ach). Changes in Qa and Qm with changes in Pa
      were analyzed, and it was found that (i) both the Pa-Qa and Pa-Qm curves, during
      the administration of TMP or CTL, show different patterns from those during the
      administration of Nicardipine or Phentolamine; (ii) the Pa-Qa and Pa-Qm curves
      after the administration of TMP or CTL show similar patterns with those after the
      administration of Ach.

PMID- 11321436
TI  - In vivo microvascular actions of Artemisia vulgaris L. in a model of ischemia
      reperfusion injury in the rat intestinal mesentery.
AB  - Water extract fractions of leaves from Artemisia vulgaris L. (commonly known as
      mugwort) were tested for their effects on tissue damage brought about by ischemia
      reperfusion injury in the rat mesentery. Male Sprague-Dawley rats, 200-300 grams
      in weight were divided into two groups, control and treatment (AV) group. All
      rats were anesthetized with ketamine HCl administered intramuscularly,
      tracheotomized and cannulated in one carotid artery and one jugular vein. After a
      midline abdominal incision, the mesenteric area was exteriorized and observed
      using videomicroscopy. After baseline observations of systemic blood pressure,
      heart rate, venular diameters and leukocyte adhesion along venules, the
      mesenteric artery and vein were occluded for 10 minutes. Prior to occlusion, A.
      vulgaris-treated animals were given a bolus injection of a 1% w/v solution of
      extracts, while the control group received saline. Monastral Blue dye was also
      administered before the occlusion at a dose of 30 mg/kg via the jugular vein in
      order to assess transendothelial leakage. Hemodynamic and cellular parameters
      were measured immediately after the release of occlusion and at 10 minute
      intervals thereafter. Results show that the extracts had no significant effects
      on mean blood pressures and heart rates, but appeared to significantly reduce
      leukocyte adherence and transendothelial leakage while improving flow in the
      ischemia-reperfused organ. The extract fractions contain yomogin, which has been
      previously shown to inhibit iNOS activity, and may therefore explain the anti
      inflammatory property of the plant.

PMID- 11321437
TI  - Phytochemical analysis and hemodynamic actions of Artemisia vulgaris L.
AB  - Artemisia vulgaris L. is widely used in the Philippines for its anti-inflammatory
      properties. The plant was cultivated and mature leaves were collected and washed.
      The dried leaves were extracted with both distilled water and chloroform. NMR
      data were obtained using a Varian Unity 500 MHz spectrophotometer. High and low
      resolution mass spectra were obtained on a Finnigan MAT 96 high resolution gas
      chromatograph/mass spectrophotometer with a MAT ICIS operating system. The leaves
      yielded 2 sesquiterpene lactones and a novel aromatic compound. Two partition
      fractions from the aqueous extracts and four partition fractions from the
      chloroform extracts were tested on male Sprague-Dawley rats using both the in
      situ mesenteric circulation and the isolated perfused mesentery. In the isolated
      perfused rat mesentery, administration of 10% w/v solutions of water extract
      fractions FGN 63-1 and FGN 63-2 of A. vulgaris were highly effective in reversing
      the hypertensive action induced by norepinephrine, but they did not change the
      regional mesenteric pressures when given at baseline. In the intact rat,
      injection of 10 mg/ml of FGN 63-1 and chloroform extract FGN 64-2 did not
      significantly alter baseline blood pressures, but were able to reverse the
      increase in mean systolic and diastolic pressures induced by norepinephrine. The
      same fractions did not exert any significant effect on heart rate in either the
      normotensive or hypertensive states. The present data suggest that aqueous and
      chloroform extracts from leaves of A. vulgaris have anti-hypertensive actions but
      have no significant effects on cardiovascular hemodynamics under basal
      conditions.

PMID- 11321439
TI  - Cytotoxic mechanism of flavonoid from Temu Kunci (Kaempferia pandurata) in cell
      culture of human mammary carcinoma.
AB  - The cytotoxic activity of flavonoid from Temu Kunci (Kaempferia pandurata) was
      tested by brine shrimp lethality test and cell culture of human mammary
      carcinoma. This compound is pinostrobin, and has antitumor activity. However, the
      critical biochemical target of these pinostrobin has not been identified. In our
      present studies, we used DNA topoisomerase I which was isolated from human tumor.
      This result showed that pinostrobin inhibited DNA topoisomerase I activity.
      Pinostrobin may be interfere with DNA breakage-reunion reaction by stabilizing a
      key covalent intermediate between DNA and the enzyme, resulting in the cleavage
      DNA. An inhibition in the activity of DNA topoisomerase I is suggesting that this
      could be a possible mechanism of pinostrobin from Temu Kunci for the cytotoxicity
      observed in cell culture of human mammary carcinoma.

PMID- 11321438
TI  - Immunostimulating effect of pule (Alstonia scholaris L. R.Br., Apocynaceae) bark
      extracts.
AB  - The immunostimulating effect of "Pule" (Alstonia scholaris (L.) R.Br.,
      Apocynaceae) bark extracts was studied in BALB/c mouse. The extracts were
      administered orally, once a day for 7 consecutive days. The results showed that
      at the same doses (50, 100 and 200 mg/kg b.w.) the aqueous extract had higher
      phagocytic index (1.39-1.79) than the ethanolic extracts (0.81-0.93) in normal
      mice. The aqueous extract at 50 mg/kg b.w. also enhanced phagocytic activity of
      immunosuppressed mice significantly (P < 0.01). At 50 and 100 mg/kg b.w. the
      extract prevents the decrease of immune system induced by prednisone. The aqueous
      extract at 100 mg/kg b.w. increased lytic activity of peritoneal exudate cells
      against Escherichia coli significantly (P < 0.05). At the doses of 50 and 100
      mg/kg b.w. the aqueous extract had no effect on primary antibody level. The
      aqueous extract at 50 mg/kg b.w. induced the cellular immune response while at
      100 mg/kg b.w. inhibited the delayed type of hypersensitivity reaction.

PMID- 11321440
TI  - Microvascular vasodilatory responses to electric acupuncture in rat brain under
      acute hemorrhagic hypotension.
AB  - The present experiment attempted to evaluate the effect of electrical acupuncture
      on the cerebral microcirculation in anesthetized rats, using fluorescence
      videomicroscopy. Changes in the pial arteriolar diameter under acute hemorrhagic
      hypotension were examined quantitatively. The present results suggest that
      acupuncture may be effective in improving the cerebral microcirculation in
      hemorrhagic hypotension.

PMID- 11321442
TI  - Changes in coagulation and tissue plasminogen activator after the treatment of
      cerebral infarction with lumbrokinase.
AB  - This paper aimed to investigate the effect of lumbrokinase on the anticoagulation
      and fibrinolysis in treating cerebral infarction. Lumbrokinase was used in
      patients with cerebral infarction. Patients were randomly divided into treatment
      group (n = 31) and control group (n = 20). Single blind method was used in this
      investigation. The Chinese stroke score was used to evaluate the results of
      treatment before and after administration of lumbrokinase. Kaolin partial
      thromboplastin time (KPTT), prothrombin time (PT), fibrinogen content, vWF
      content were analyzed, and tissue plasminogen activator (t-PA) activity,
      plasminogen activator inhibitor (PAI) activity, D-dimer level were assayed. In
      both groups, the stroke score decreased after administration, but in the
      treatment group, it was more obvious. In the treatment group, KPTT was prolonged,
      t-PA activity and D-dimer level increased, while the content of fibrinogen
      decreased significantly. There were no significant changes of PT and PAI activity
      in both groups. It is concluded that lumbrokinase is beneficial to the treatment
      of cerebral infarction. The effect of lumbrokinase is related to the inhibition
      of intrinsic coagulation pathway and the activation of fibrinolysis via an
      increase of t-PA activity.

PMID- 11321441
TI  - Endothelial cell dysfunction in microvasculature: relevance to disease processes.
AB  - Functional and morphological alterations of microvascular endothelial cells (ECs)
      would lead to microcirculatory disturbances, thereby providing a basis for the
      development of a disease state. Clinically endotoxemia frequently encountered in
      a variety of diseases is considered to be a trigger to develop the
      microcirculatory disorders such as disseminated intravascular coagulation (DIC)
      and multiple organ failure (MOF), both of which feature the end stage of severe
      systemic disease. Experimentally intravital microscopy reveals that continuous
      venous infusion of endotoxin (LPS) causes a low flow state in the rat mesenteric
      microcirculatory unit. By vital stain with monastral blue B (MBB), the
      microvascular ECs are focally positive for MBB at the postcapillary venular site,
      where leukocytes adhere and extravasate. As shown in the histamine-induced
      diapedesis by transmission electron microscopy, the MBB-positve venular ECs may
      correspond to the contracted ECs, enabling the polymorphonuclear leukocytes and
      erythrocytes to extravasate through the widened gaps between the contracted ECs.
      Actin filaments proven in the microvascular ECs by electron microscopy may play a
      modulating role in this neutrophil diapedesis. In the process of gastric ulcer
      formation under restrained stress to the rat, the ECs of microvessels in the
      gastric mucosa, particularly of the mucosal capillaries and postcapillary venules
      directly innervated by the cholinergic nerves, are altered by the stress-induced
      overstimulation of the autonomic nerves, inducing the diapedesis of leukocytes
      and erythrocytes followed by hemorrhagic and ischemic injuries in the gastric
      mucosa. Liver cirrhosis also accompanies endotoxemia. The most prominent electron
      microscopic alterations of hepatic microvasculature are a decrease of hepatic
      sinusoidal endothelial fenestrae (SEF) both in diameter and in number, and the
      formation of basement membranes beneath the hepatic sinusoidal ECs. These
      ultrastructural changes would be induced by a most potent vasoconstrictor
      endothelin (ET)-1 through the overexpressed ET(A) and ET(B) receptors on the
      hepatic stellate cells and the sinusoidal ECs, contributing to the development of
      portal hypertension as well as to the disturbance in excretion of endotoxin into
      the bile canaliculi via the hepatocytes from the circulating sinusoidal blood to
      prevent endotoxemia.

PMID- 11321443
TI  - Lipoate ameliorates ischemia-reperfusion in animal models.
AB  - Ischemia and reperfusion were studied in isolated working rat hearts and in
      exarticulated rat hind limbs. Free radicals are known to be generated in
      ischemia/reperfusion and to propagate complications. To reduce reperfusion
      injury, conditions were ameliorated including the treatment with antioxidants,
      lipoate or dihydrolipoate. In isolated working rat hearts, cardiac and
      mitochondrial parameters are impaired during hypoxia and partially recover in
      reperfusion. Dihydrolipoate, if added into the perfusion buffer at 0.3 microM
      concentration, keeps the pH higher (7.15) during hypoxia, as compared to controls
      (6.98). This compound accelerates and stabilizes the recovery of the aortic flow.
      With dihydrolipoate, ATP synthesis is increased, ATPase activity (ATP hydrolysis)
      reduced, intracellular creatine kinase activity maintained and thus
      phosphocreatine contents are higher than in controls. For exarticulated rat hind
      limbs, the dihydrolipoate group contained 8.3 microM in the modified reperfusate.
      Recovery of the contractile function was 49% vs. 34% in controls and muscle
      flexibility was maintained whereas it decreased by 15% in the controls. Release
      of creatine kinase from cells was significantly lower with dihydrolipoate.
      Lipoate/dihydrolipoate effectively reduced reperfusion injury in isolated working
      rat hearts and in exarticulated rat hind limbs after extended ischemia. Finally,
      the compound was successfully applied in an in vivo pig hind limb model.

PMID- 11321444
TI  - Immunogenetics of peripheral arteriopathies.
AB  - Takayasu's arteritis (TA) and thrombangiitis obliterans (Buerger's disease) are
      idiopathic, inflammatory arteriopathies with strong indications for the
      involvement of autoimmunity and host genetic factors in their immunopathogenesis.
      The exact etiology of these arteriopathies still remains unknown even after
      almost nine decades of their description. A series of immunogenetic studies
      conducted worldwide seeking to define genetic factors in governing immune
      response in these diseases have yielded conflicting results on the involvement of
      HLA molecules. While an association of HLA-B5 or its molecular subtypes with
      Takayasu's arteriitis has been emphasized in patients from Japan, Korea and
      India, no such association has been reported in Mexican and North American
      patients. On the other hand, a limited data is available on the association of
      HLA antigens with Buerger's disease. In this article, we provide an overview of
      the immunogenetics of Buerger's disease and Takayasu's arteriitis in the context
      of studies in North Indian patients and those in other ethnic groups. Our studies
      indicate a positive association of Takayasu's arteriitis with the HLA-B5 molecule
      with no preferential association with its two major subtypes. In Buerger's
      disease, we have observed a strong positive association with HLA-DRB1*1501
      consistent with the findings in Japanese patients. These results suggest an
      important role of HLA linked factors in governing susceptibility to both
      arteriopathies.

PMID- 11321445
TI  - Diagnosis and treatment in the management of chronic venous insufficiency.
AB  - Chronic venous insufficiency (CVI) is caused mainly by an alteration in the
      elasticity of venous walls and the dysfunction of venous valves. The diagnosis
      and treatment for CVI management are discussed in this paper.

PMID- 11321446
TI  - Pathophysiology of microcirculation in venous disease.
AB  - Microcirculatory disturbances lead to chronic ulceration of the leg, and this
      symptom is a sign of a chronic venous insufficiency (CVI), caused by increased
      leg vein pressure and continous changes in vein pressure, which need medical
      treatment, and if a chronic capillary reaction present, treatment by applying a
      graduated compression bandage of the leg is mandatory. Subcutaneous tissue
      hypoxaemia and interstitial edema lead to worsening of the ulcer and need
      intensive and systematic wound care, because unhealed chronic wound with trophic
      changes of the skin is the major cause of further CVI changes of the leg. As
      chronic venous disease has complex etiologic basis, it needs diagnostics and
      treatment modality based on various approaches, and that microcirculatory
      pathophysiological approach should be considered in all kinds of the treatment of
      chronic venous insufficiency. Microcirculation pathology should be used as an
      approach in the treatment regiment of CVI, whilst the basic pathophysiology of
      the venous diseases, which is known as one of the causes of CVI. This approach
      will give better results of treatment and other pathologic disturbances which
      were caused by chronic vitious circle chain processes.

PMID- 11321447
TI  - Effects of exercise on rheological and microcirculatory parameters.
AB  - The physiological changes occurring during exercise and its possible consequences
      have been receiving considerable attention lately. In this paper, we studied the
      changes in hemorheological and microcirculatory parameters, before and after the
      exercise, in the subjects undergoing mild exercise (n = 20). A cycle ergometer
      adjusted at 2.5 kilopounds was used for 15 minutes. The whole blood viscosity
      showed a significant increase after exercise at all shear rates (0.512-51.2/s)
      except at the high shear rate (94.5/s). However, the significant level was more
      (P < 0.005) at low shear rates (0.512-4.39/s). A significant elevation in plasma
      viscosity was observed after the exercise (P < 0.0008). Red cell rigidity showed
      a significant increase after the exercise (P < 0.001) while red cell aggregation
      and hematocrit failed to show any significant change. Microcirculatory studies
      showed a significant increase in the basal perfusion level after exercise (P <
      0.0002) when compared to the resting state value. There was a significant
      decrease in reactive hyperaemia perfusion index after exercise (P < 0.0007).
      Hence, it is evident from this study that short-term exercise significantly
      alters hemorheological and microcirculatory parameters.

PMID- 11321448
TI  - Anticancer treatment of endostatin gene therapy by targeting tumor neovasculature
      in C57/BL mice.
AB  - Antiangiogenesis strategy has been widely recognized as a viable approach to
      fight cancer. Considering the high cost and inconvenience of protein therapy of
      endostatin (ES), which is a potent antiangiogenic protein, we attempted to
      explore the inhibitory effect of ES gene therapy on tumor growth and metastasis.
      In this experiment, Lewis lung carcinoma (LLC)-bearing C57/BL mice were used to
      evaluate the antitumor effect of ES gene therapy and its impairment of tumor
      neovasculature. The data showed that the ectopic ES in circulation expressed by
      intramuscular administration of formulated ES-encoding plasmid DNA significantly
      suppressed primary tumor growth and lung metastasis in LLC-bearing C57/BL mice.
      Hence, our results demonstrated the inhibitory effect of ES gene therapy on
      angiogenesis-dependent tumor growth and metastasis.

PMID- 11321449
TI  - Peroxynitrite leads to arteriolar smooth muscle cell membrane hyperpolarization
      and low vasoreactivity in severe shock.
AB  - This paper aimed to study the mechanism of vascular hyporeactivity during severe
      hemorrhagic shock. Rats were divided into control and shock group. Membrane
      potential of arteriolar strips was measured with intracellular recording method
      and membrane potential changes in arteriolar smooth muscle cells (ASMC) were
      recorded with membrane potential sensitive fluorescent dye (DiBAC4) and confocal
      microscopy. Hyperpolarization of ASMC membrane appeared at the late stage of
      shock, which correlated to low vasoreactivity. Glybenclamide, an inhibitor of
      K(ATP) channel reversed the hyperpolarizing effect. S-nitroso-N
      acetylpenicillamine (SNAP), a donor of NO, in a higher concentration (400 mol/l)
      caused membrane hyperpolarization in control and shock group, which was
      completely reversed by application of Tiron, a scavenger of O2-. The
      hyperpolarizing effect of SNAP was decreased by ODQ, glybenclamide and (or)
      charybdotoxin. It is concluded that hyperpolarization of ASMC leads to vascular
      hyporeactivity. Peroxynitrite (OONO-) involves in the development of
      hyperpolarization in severe shock. The production of cGMP and activation of
      K(ATP) and K(Ca) channel contribute to the hyperpolarizing effect of OONO-*.

PMID- 11321450
TI  - Effects of adrenomedullin on the cardiac performance and coronary flow in an
      isolated perfused rat heart model.
AB  - The effect of adrenomedullin (AM) on the cardiac performance and coronary flow
      were studied in an isolated perfused rat heart model based on the modified
      Langendorff method. The heart rate (HR), electrocardiogram (ECG), left
      ventricular contraction (LVC) (dP/dt), and coronary flow (CF) were measured
      before and after the application of AM. The effect of AM on the coronary flow was
      examined in the model with and without endothelial degradation, using different
      inhibitors such as N(G)-nitro-L-arginine, glibenclamide, and indomethacin. The
      present results indicated that AM increased HR and CF, but decreased LVC
      significantly, while it had no effect on ECG. The vasodilatory effect of AM was
      discussed in views of endothelial-dependence due to nitric oxide and K+ channel
      activation.

PMID- 11321451
TI  - Relaxation effect of nitric oxide-donor on diabetic penile smooth muscle in
      vitro.
AB  - The primate model has been used for investigations on the physiology and
      pharmacology of erection. Recent in vitro investigations indicate that nitric
      oxide (NO)-donor act as the mediator of penile erection, but it is unclear
      whether NO-donor could enhance the relaxation effect of sildenafil on diabetic
      penile smooth muscle. To determine the relaxation effect of NO-donor on diabetic
      penile smooth muscle, we studied strips of corpus cavernosum tissue obtained from
      15 diabetic cynomolgus monkey (Macaca fascicularis). Contraction was induced on
      isolated strips of corporal smooth muscle by norepinephrine; then relaxation was
      assessed with the administration of two agents: selective phosphodiesterase type
      5 (PDE5) inhibitor (sildenafil citrate) and S-nitroso-N-acetylpenicillamine
      (SNAP), an NO-donor, and combination of both agents. Analysis of variance was
      used to compare the responses to the different agents under various treatments.
      It was concluded that NO-donor could not enhance the relaxation effect of
      sildenafil on corpus cavernosum of diabetic monkey.

PMID- 11321452
TI  - The role of nitric oxide in the mechanism of penile erection.
AB  - This paper aimed to evaluate the significance of nitric oxide (NO) in the
      physiology of the penis. Pudendal arteries and penile cavernous tissue of the
      Macaca nemestrina pertaining to NO were examined in the view of molecular biology
      and physiology. The results showed that potential resources of NO were in the
      neuron, sinusoidal endothelium and corporal smooth muscle cells of the penis. NO
      exerted a host of functional roles by binding with specific molecular targets. It
      was concluded that NO exerts a significant role in physiology, especially in the
      microcirculation of the penis, as the principal mediator of erectile function.

PMID- 11321453
TI  - Mechanism of free radicals on the molecular fluidity and chemical structure of
      the red cell membrane damage.
AB  - This paper investigated the mechanism for the rheological dysfunction of red
      blood cell (RBC) caused by free radicals. Normal RBCs were collected from healthy
      volunteers. Fenton system was added to the RBCs and allowed to react for 30
      minutes in vitro. The RBC membrane molecules were damaged due to the free
      radicals reaction. It was found that: (1) The protein configurations changed such
      as the ratio decreasing in alpha-helix and increasing in both of beta-sheet and
      coiled-coil; (2) -P=O/-P-O chemical group ratio in phospholipids increases; (3)
      the molecular rotational correlation times of proteins and lipids were extremely
      elevated; (4) the membrane shear elastic modulus was significantly enhanced. The
      present results support that the chemical structure changes led by free radicals
      are ultimately responsible for the reduction in molecular fluidity of RBC
      membrane.

PMID- 11321454
TI  - Microcirculatory characterization of cerebral angiogenesis in mice using
      intravital videomicroscopy.
AB  - The present study investigated microcirculatory characteristics of the cerebral
      neovasculature induced in mice, using basic fibroblast growth factor (bFGF) and
      platelet derived growth factor (PDGF). The nylon-mesh sandwich (collagen
      gel/growth factor in bovine serum albumin embedded in between two nylon-mesh
      pieces) was used to induce angiogenesis. After different days of incubation, the
      observations of neocapillaries were done on the upper surface of the nylon-mesh,
      using fluorescence video-microscopy. The neocapillary diameter, red cell
      velocity, and the neocapillary density were evaluated based on the video-image.
      The neocapillaries were visible on the upper surface of the mesh on the 6th day
      after the incubation, and red cells started to flow from the day 7. The
      neocapillary red cell velocity increased with days after incubation, but its
      level was less than that of the pre-existing capillaries. The neocapillary
      diameter decreased as the neocapillaries got matured. The neocapillary density
      was dependent on the doses of bFGF and PDGF. The neocapillary diameter did not
      alter with the higher concentration as well as with different growth factors.
      Both bFGF and PDGF showed an increase in red cell velocity at high concentration.

PMID- 11321455
TI  - Gene transfer of vascular endothelial growth factor plasmid/liposome complexes in
      glioma cells in vitro: the implication for the treatment of cerebral ischemic
      diseases.
AB  - Vascular endothelial growth factor (VEGF) is most promising in therapeutic
      angiogenesis for ischemic vascular disease. This paper aimed to study VEGF gene
      therapy for the treatment of cerebral ischemia. The glial cell was chosen as the
      target cell for gene transfer, and the expression of VEGF was studied in vitro.
      VEGF plasmid/liposome complexes were constructed by mixing VEGF plasmid with
      liposome, and then cultured C6 glioma cells were transfected with these complexes
      by lipofectamine method. As control, the same kind of cells were exposed to
      liposome only. Immunohistochemistry was performed to both groups at 24, 48 and 72
      hours after transfection. The transfected cells expressed VEGF significantly
      higher than the control. The present result demonstrated the feasibility of
      choosing the glial cell as the target cell for VEGF gene transfer, and found the
      rationale for the cerebral VEGF gene therapy.

PMID- 11321456
TI  - Role of nitric oxide in the control of cerebral microcirculation under
      physiological and pathological conditions.
AB  - Effect of nitric oxide (NO) on vasomotor tone of cerebral parenchymal arterioles
      was studied in rats. Then, the role of NO was clinically investigated in the
      pathogenesis of progressive cerebral vascular occlusive disease, moyamoya
      disease. In rat, the cerebral arterioles, about 30-60 microm in diameter, were
      dilated by L-arginine, a precursor of NO, at concentrations as low as 0.1
      micromol with maximal dilation of 14% at 100 micromol. The arterioles were
      constricted by N(G)-monomethyl-L-arginine (L-NMMA), a NO synthesis inhibitor.
      Superoxide dismutase, which seems to protect NO from inactivation, increased
      sensitivity of L-arginine. Compared with control specimens of cerebral spinal
      fluid (CSF) obtained from 16 patients, concentrations NO metabolites in the CSF
      of 23 patients with moyamoya disease were significantly higher. NO metabolites
      concentrations obtained during initial surgery decreased during a second,
      contralateral procedure. NO plays an important role in the regulation of basal
      tone of cerebral parenchymal arterioles and contributes to the increase in
      collateral circulation in cerebral occlusive disease like moyamoya disease.
      Vascular bypass surgery can reduce NO metabolites together with abnormal
      collateral circulation.

PMID- 11321457
TI  - Microcirculatory responses to repeated embolism-reperfusion in cerebral
      microvessels of cat: a fluorescence videomicroscopic study.
AB  - Intra-carotid injections of degradable starch microspheres (DSMs) can induce DSM
      embolism-reperfusion in the level of cerebral arterioles. Vascular responses of
      cerebral arterioles to repeated DSM embolism (ischemia)-reperfusion were examined
      when DSMs were injected twice through a carotid artery with a time interval of 30
      min. Arteriolar diameter was measured from images of arterioles filled with
      rhodamine-B isothiocyanate dextran and red cell velocity was measured with a dual
      window technique using FITC-labeled red cells as a flow tracer. DSM embolization
      induced ischemia (flow reduction including stasis) for approximately 10 min in
      the level of microvessels (arterioles). Cerebral arterioles began to dilate
      immediately after embolism induced by the DSM injection and vasodilation was
      sustained until reperfusion. After reperfusion the arteriole began to constrict
      and the arteriolar diameter returned to the initial diameter level at
      approximately 20 min after the DSM injection. The arteriolar diameters for the
      second DSM embolism showed a similar response to those for the first embolism in
      7 out of 8 cats. It can be concluded that the vascular response of cerebral
      arterioles to the second embolism-reperfusion could not be affected by the first
      embolism-reperfusion.

PMID- 11321458
TI  - Effects of blockade of cerebral lymphatic drainage on cerebral ischemia after
      middle cerebral artery occlusion in rats.
AB  - This experiment aimed to investigate the effects of blockade of cerebral
      lymphatic drainage on cerebral ischemic damage. Seventy six Wistar rats were
      divided randomly into middle cerebral artery occlusion (MCAO) group and MCAO plus
      cerebral lymphatic blockade (MCAO+CLB) group for the experiment. The contents of
      water and electrolytes, the activity of superoxide dismutase (SOD) and the
      content of malondialdehyde (MDA) in the ischemic brain tissue were detected at
      24, 48 and 72 hours after the operation. The morphologic examination was also
      performed. In MCAO group, contents of water, sodium and calcium in the ischemic
      brain tissue increased significantly at any time after the operation. The SOD
      activity decreased while the MDA content increased markedly. The morphologic
      findings showed severe damage of ischemic brain tissue and neurons. In MCAO+CLB
      group, the above parameters were altered more obviously. The present observation
      suggests that blockade of cerebral lymphatic drainage may deteriorate ischemic
      brain damage after MCAO.

PMID- 11321459
TI  - Effects of leg rotation on lymph flow and pressure in rabbit lumbar lymph
      circulation: in vivo experiments and graphical analysis.
AB  - The intraluminal lymphatic pressure in rabbit lumbar lymphatic trunks was
      determined. To estimate the lymphatic pressure, graphical analysis was performed
      from lymph outflow pressure-flow rate relationship and lymph infusion pressure
      flow rate relationship. A direct measurement technique with a T-tube was also
      carried out to measure the pressure in the lumbar lymphatic. The rabbit leg was
      passively rotated at 0.3 Hz in the diameter of 8 cm to enhance the lymphatic pump
      activity of the leg. The estimated pressure and measured pressure in the
      lymphatics were 6.50 and 7.14 +/- 2.38 cmH2O, respectively. It was confirmed that
      similar values could be obtained from these two methods. The lymphatic pumping in
      the leg may affect a distribution of pressure in the lumbar lymphatic system.

PMID- 11321460
TI  - Changes in the microcirculation at the superficial and deeper levels in
      lymphoedema: the effects and results of massage, compression, exercise and
      benzopyrones on these levels during treatment.
AB  - This review starts with a brief description of the pioneering work done by J.R.
      Casley-Smith when he looked at the pathophysiological changes that occur, and
      transport from the blood vessels, through the interstitium to the lymphatics and
      lymphatic uptake, with the electron microscope. Collaboration with, and further
      work by many colleagues producing a better understanding of lymphatic drainage,
      have led to this work being applied in the treatment of lymphoedema.

PMID- 11321461
TI  - In vivo identification of parasinus macrophages in the mesenteric lymph node.
AB  - Macrophages beneath the marginal sinus in the lymph nodes may play a role in
      defense against microorganism. The purpose of this study was to directly
      visualize the parasinus macrophages in the mesenteric lymph node. Fluorescent
      latex particles were injected into the appendix submucosa of rats. The mesenteric
      lymph node was epi-illuminated and observed with a fluorescent microscope.
      Fluorescent particles entered the marginal sinus of the mesenteric lymph node
      through the afferent lymphatic vessels, and distributed diffusely all over the
      marginal sinus. The particles became aggregated and interspersed 3 hr after
      injection, suggesting that particles were incorporated by phagocytes. The number
      of these particle-laden phagocytes increased up to 12 hr after injection, and
      then declined. Some phagocytes migrated rapidly within the marginal sinus.
      Morphology of these phagocytes in cell suspension was consistent with
      macrophages. In conclusion, we successfully visualized parasinus macrophages in
      vivo, which incorporated foreign bodies and migrated within the marginal sinus.

PMID- 11321462
TI  - The role of the microlymphatic valve in the propagation of spontaneous rhythmical
      lymphatic motion in rat.
AB  - Male Wistar rats (n = 12) with the mesenteric preparation were used to
      quantitatively investigate the characteristics of wave-like propagation of
      spontaneous rhythmical lymphatic motion and to explore the mechanism of
      microlymphatic valve on the activity of lymphatic motion. The dynamical behaviors
      of collecting lymphatics were visualized by a closed circuit TV system. The
      frequency, amplitude, and phase angle of the diameter oscillation, the spreading
      speed of peristaltic wave and the contractile index (CI) of rhythmical lymphatic
      motion were measured and calculated by the image processing system. The lymphatic
      segment between two adjacent valves, named by lymphangion, was a basic unit of
      microlymphatic activity. The present results revealed that there was a wave-like
      propelling of the contractile activity progressively from one lymphangion to the
      next. No significant characteristic differences were observed from the two
      adjacent lymphangion units except the increasing contractile index. The motion
      wave propagation from upstream over a valve to down stream led to a significant
      phase angle change. The pacemaker site of lymphatic motion seemed to be at the
      inlet side of the valve in each lymphangion unit. The contractile motion wave
      propagated just within each lymphangion unit. The lymph flow over the valve
      converted the pressure changes between two adjacent lymphangions and stimulated a
      new contraction wave at the next inlet site of valve. The endothelium response to
      wall tension and shear stress alteration near the inlet valve site might be one
      of the pacemaking mechanisms of lymphatic motion.

PMID- 11321463
TI  - Development of hemorheology: perspective in instrumentation development.
AB  - New viscometers for blood viscometry, improved intravital microscope, and related
      instruments, which are capable of measuring important rheological factors for
      microcirculatory research were developed and applied for hemorheological studies.
      As the results, four major determinants of the suspension viscosity were
      determined and the role of suspension viscosity of the blood as a function of
      microcirculatory flow was clarified. Meanwhile, the use of fluorescence
      microscopy and digitized video microscopic techniques has allowed the
      investigation of the structure and function of cells at the level of the single
      intact living cell. In addition, the developments and applications of laser
      confocal microscopy provided for not only three-dimensional image construction,
      but also four-dimensional image construction. In recent years, the dramatic
      advances in molecular biology and instrumental technology have made it possible
      to probe the structural and functional bases of cellular events at the molecular
      level. The ultimate understanding of biorheological behavior is dependent upon a
      molecular basis. In the future, the use of molecular biological techniques and
      nanotechnology (e.g., laser tweezers, atomic force microscopy and near-field
      microscopy, etc.) will allow the understanding of normal and abnormal rheological
      properties of cells, tissues, organs, and systems at the molecular level, and
      will contribute to progress in biomedical science.

PMID- 11321464
TI  - Local regulators of hepatic sinusoidal microcirculation: recent advances.
AB  - This article reviews our recent studies on the local regulation of hepatic
      microcirculation with special reference to the inlet sphincter-like structures,
      the roles of sinusoidal endothelial cells and the mechanism of dynamic changes in
      the sinusoidal endothelial fenestrae (SEF) as well as in the terminal portal
      venules and the terminal hepatic arterioles induced by the potent vasoconstrictor
      endothelin (ET)-1. There are two types of sphincter-like structures at the
      entering sites of hepatic sinusoids. One is located at the junction between the
      terminal portal venule and the sinusoid, and is characterized by the large
      endothelial cells surrounded with Ito cells (hepatic stellate cells: HSCs). The
      other is located at the junction between the terminal hepatic arteriole and the
      sinusoid, and corresponds to the precapillary sphincter since our
      enzymohistochemical demonstration of arterial capillaries in close association
      with the sinusoids combined with intravital microscopy has revealed that the
      terminal hepatic arteriole directly terminates in the sinusoid. It is essential
      for the local control of hepatic sinusoidal blood flow that the dynamic
      contracting and relaxing changes not only in these inlet sphincter-like
      structures but also in the SEF correspond with those of the HSCs, both of which
      are mediated by the sinusoidal endothelium-derived vasoconstrictor endothelins
      (ETs) and vasodilator nitric oxide (NO). The contractility of the SEF and HSCs
      depends on the intracellular Ca++-calmodulin-actomyosin system.

PMID- 11321465
TI  - Adrenomedullin: a new peptidergic regulator of the vascular function.
AB  - Adrenomedullin (AM) is a vasodilator peptide first identified in pheochromocytoma
      tissue, but endothelial cells and vascular smooth muscle cells actively secrete
      AM in addition to expressing AM receptors. AM dilates blood vessels through its
      direct action on the smooth muscle and the endothelial cell-mediated nitric oxide
      pathway. We have further demonstrated that AM is synthesized and secreted from
      macrophages, fibroblasts, cardiomyocytes and many other types of cells. AM
      secretion from these cells as well as the vascular wall cells are commonly
      stimulated with inflammatory cytokines and lipopolysaccharide. AM receptor is
      also widely distributed, and AM is shown to regulate production of inflammatory
      cytokines and cell growth. Based on these data, AM is deduced to be a multi
      functional peptide participating in the regulation of vascular tone, inflammation
      and other physiologic events of the vasculature.

PMID- 11321466
TI  - Evidence of Qi-gong energy and its biological effect on the enhancement of the
      phagocytic activity of human polymorphonuclear leukocytes.
AB  - In order to test for an effect of phosphate buffered saline (PBS) treated
      externally with Qi energy ("Qi-treated" PBS) on the phagocytic activity of human
      polymorphonuclear leukocytes (PMNs), rigorously controlled experiments employing
      masking and randomized procedures were carried out under independent monitoring.
      In all experiments, Qi treatment was externally applied under monitoring to newly
      purchased unopened 100 ml bottles of PBS, and the PMN phagocytic activity was
      assayed by one experimenter in masked, randomized and monitored conditions using
      a highly sensitive chemiluminescence method. Phagocytic activity data were
      obtained in triplicate for each sample and then statistically analyzed. The PBS
      samples Qi-treated by the Qi-gong master and by one of the Qi-gong trainees
      showed clear stimulation of PMN phagocytic activity which was significant
      statistically, and this phenomenon was highly reproducible. Out of 10 experiments
      by the Qi-gong master, only twice did Qi-treatment fail to influence the PBS. The
      activity of Qi-treated PBS decayed over days or weeks. Furthermore, it was found
      that Qi-treated PBS had decreased phagocytic stimulatory activity after microwave
      treatment, but not after autoclave treatment. We also demonstrated that microwave
      irradiation and infrared laser pulse irradiation have similar effects on PBS as
      Qi-treatment. The results obtained in this experiment provide evidence of the
      existence of Qi energy, its ability to influence an electrolyte solution and its
      biological effect. Furthermore, microwave or infrared laser pulse treatment was
      found to partly mimic the Qi-treatment of PBS.

PMID- 11321467
TI  - Anti-oxidative herbs and indomethacin-induced rat gastric mucosal lesions:
      protection by GamiHyangsa-Yukgunja.
AB  - This study investigates the protective effects of GamiHyangsa-Yukgunja (GHY, a
      popular herbal medicine formula) on indomethacin-induced gastric mucosal lesions
      and morphological change in rats. Subcutaneous injection of indomethacin (25
      mg/kg) produced the following gastric morphological alterations: mucosa
      hemorrhagic infarct, mucosa cell necrosis, leukocyte infiltration, mucosa
      hemorrhagic erosion, and gastric pit disappearance. Tissue damages were
      accompanied by increased oxidative stress, lipid peroxidation, and decreases in
      superoxide dismutase (SOD), and catalase (CAT) activities, and glutathione (GSH)
      concentrations. Our results show that pretreatment of the rats with orally
      administered GHY extract (3.3 ml/kg/day) significantly reduced gastric lesion
      formation and caused the amelioration of several pathological changes in the
      above-mentioned gastric mucosal lesions. Concomitantly, GHY-pretreatment
      increased gastric mucosal SOD and CAT activities and GSH concentrations. We
      therefore propose that GHY exerts a prophylactic effect on the indomethacin
      induced gastric mucosal lesions by enhancing antioxidant defense systems.

PMID- 11321468
TI  - The inhibitory effect of herbal medicine -Dai Kenchu To (DKT)- on the colonic
      motility in rats in vitro.
AB  - Dai-Kenchu-To (DKT) is a herbal medicine and is currently used as the treatment
      of paralytic ileus in Japan. We investigated the mechanism of beneficial effects
      of DKT in vitro. DKT-extract powder (DKT-EP; 30-300 microg/ml) caused a
      significant inhibition on carbachol (CCH: 10(-6))-induced contraction in a
      concentration dependent manner of the rat distal colon. DKT-EP (100 microg/ml)
      consists of 20 microg/ml of Zanthoxylum Fruit, 30 microg/ml of Ginseng Root and
      50 microg/ml of Ginger Rhizome. Although each of them had no effect on CCH
      induced muscle contraction, the combination of three ingredients caused a
      significant inhibition on CCH-induced contraction.

PMID- 11321469
TI  - Effects of coffee cherry, the residue left after removal of the beans from the
      coffee fruit, on mammary glands, automatic behavior and related parameters in
      mice.
AB  - To clarify the mechanisms of the anti-mammary tumor activity of coffee cherry
      (CC), the residue left after the removal of beans from the fruit, the effects in
      SHN mice of CC on plasma and urine component levels, mammary gland growth,
      spontaneous motor activity and several related parameters were examined. Hot
      water extract of CC was given to 2-month-old mice in drinking water (0.5%) for 60
      days. The treatment prevented the elevation of plasma and urine levels of alanin
      amino-transferase and asparate aminotransferase, indicating that CC can protect
      against metabolic abnormality, which is a cause of the high mammary tumor
      susceptibility of SHN mice. It also resulted in an inhibition of the formation of
      precancerous mammary hyperplastic alveolar nodules. Neither food and water intake
      nor spontaneous motor activity was affected by CC. The findings provide novel
      information on the mechanism of the protective effect of CC on mammary
      tumorigenesis and confirm the usefulness of CC as a safe chemopreventive agent of
      mammary and other types of tumors.

PMID- 11321470
TI  - Anti-allergic activity of the Sophorae radix water extract in experimental
      animals.
AB  - The water extract of Sophorae radix was tested for its preventive effects against
      cardiovascular anaphylaxis elicited in experimental animals. In actively
      sensitized pithed rats, the extract partially protected the animals from death
      resulting from antigen challenge. Of the cardiovascular changes observed during
      the anaphylaxis in the pithed animals, the initial pressor response was
      significantly attenuated by the extract. The extract also improved anaphylactic
      cardiac dysfunction in passively sensitized isolated guinea hearts: improvement
      was noted in the contractility, arrhythmic duration and lactate dehydrogenase
      elevation. The perfusion pressure change to antigen challenge was not altered by
      the extract in passively sensitized isolated mesenteric artery preparations. The
      extract however significantly inhibited homologous passive cutaneous anaphylaxis
      responses in rats. When examined in isolated guinea pig tracheal muscle, the
      extract did not influence at reasonable concentrations on the contraction
      elicited by three major anaphylactic mediators, histamine, leukotriene D4 and
      serotonin. These results suggest that the water extract of Sophorae radix
      possesses anti-anaphylactic effect in cardiovascular system, primarily acting on
      the heart not the peripheral resistance vessels.

PMID- 11321471
TI  - Effects of Orengedoku-to and Senkanmeimoku-to, traditional herbal medicines, on
      the experimental elevation of aqueous flare in pigmented rabbits.
AB  - We investigated the effects of Orengedoku-to (Huanglian-Jie-Du-Tang in Chinese)
      and Senkanmeimoku-to (Xygan-Ming-Mu-Tang in Chinese), traditional herbal
      medicines, on experimantal elevation of aqueous flare in pigmented rabbits. To
      produce the elevation of aqueous flare in rabbits, prostaglandin E2 (PGE2) was
      applied to the cornea with use of a glass cylinder, or lipopolysaccharides (LPS)
      were injected into the ear vein. Animals were pretreated by the oral
      administration of 150 g/day of food containing 0.7%, 0.2% or 0.07% (w/w)
      Orengedoku-to, or 2%, 0.6% or 0.2% (w/w) Senkanmeimoku-to for 5 days. Aqueous
      flare was measured with a laser flare-cell meter. Pretreatment with 0.7% or 0.2%
      Orengedoku-to and 2% Senkanmeimoku-to did suppress significantly (P < 0.05)
      elevation of aqueous flare induced by PGE2. Pretreatment with 0.7% or 0.2%
      Orengedoku-to and 2% or 0.6% Senkanmeimoku-to significantly suppressed (P <
      0.001) elevation of aqueous flare induced by LPS. It is possible that Orengedoku
      to and Senkanmeimoku-to may migrate some forms of uveitis.

PMID- 11321472
TI  - Effect of American ginseng extract (Panax quinquefolius) on formalin-induced
      nociception in mice.
AB  - Twenty-three ICR mice were force fed orally with American ginseng extract, Panax
      quinquefolius, (Cold FX) for 4 days. Another 20 mice were fed with water as
      placebo in a similar fashion. Formalin tests which yield typically two phases of
      pain behavior were done in both groups. Although there was no difference in the
      first phase between groups, mice treated with Cold FX spent significantly less
      time in licking and biting of the injured paws in the second phase. The data
      indicate that American ginseng may have analgesic effect in this chronic pain
      model.

PMID- 11321473
TI  - Effects of Ginsenoside Rb2 and Rc on inferior human sperm motility in vitro.
AB  - The purpose of the study was to investigate the effects of two constituents of
      Panax notoginseng flower extract, Ginsenoside Rb2 and Rc, on human sperm motility
      and progression in vitro. Semen samples were collected from 20 patients with
      sperm motility between 20% and 40% of normal. All samples had sperm counts of
      over 20 million per milliliter, in accordance with the World Health Organization
      standard. Sperm were separated by a Percoll discontinuous gradient technique, and
      divided into a Percoll sperm control group, and three Ginsenoside Rb2
      experimental groups (0.1, 0.01 and 0.001 mg/ml) and three Ginsenoside Rc
      experimental groups (0.1, 0.01 and 0.001 mg/ml). The results showed that at
      concentrations of 0.01 mg/ml and 0.001 mg/ml, Ginsenoside Rc enhanced both sperm
      motility and sperm progression significantly at the end of the 1st and 2nd hour.
      However, the three concentrations of Ginsenoside Rb2 did not increase sperm
      motility at the 1st or 2nd hour, but promoted sperm progression at the 2nd hour,
      when compared to the Percoll group.

PMID- 11321475
TI  - Effects of emitted Qi on in vitro natural killer cell cytotoxic activity.
AB  - The present study investigated the effects of Korean Qi-therapy, ChunSoo Energy
      Healing, on natural killer (NK) cell cytotoxicity in vitro depending on Qi
      treatment time and the types of cells treated. NK cell cytotoxicity was assayed
      by measuring LDH release from tumor target cells (K562 cell lines). NK activity
      was significantly increased by emitted-Qi treatment of 30 sec duration. Three and
      5 minutes of Qi projection created the greatest increase in NK cell activity when
      mixtures of NK cells and K562 cells were treated (1.81 and 2.12 fold for 4 hr
      culture; 1.54 and 1.36 for 16 hr culture, respectively). NK cell activity
      increased significantly in Qi-treated K562 cells alone (1.13 fold, p<0.05)
      compared to control. These results are consistent with in vivo Qi-therapy on
      humans and suggests that emitted-Qi has an acute stimulatory effect on NK cell
      activity. This study provides direct scientific support that Qi as such may
      positively affect human cellular immunity.

PMID- 11321474
TI  - Effect of norcantharidin on N-acetyltransferase activity in HepG2 cells.
AB  - The inhibition ofarylamine N-acetyltransferase (NAT) activity by norcantharidin
      (NCTD), the demethylated form of cantharidin, in human hepatocellular carcinoma
      HepG2 cells was investigated. By using high performance liquid chromatography,
      NAT activity on acetylation of 2-aminofluorene (AF) and p-aminobenzoic acid
      (PABA) were examined. Two assay systems were performed, one with cellular
      cytosols, the other with intact HepG2 cell suspensions. The NAT activity in HepG2
      cell line was inhibited by norcantharidin in a dose-dependent manner in both
      types of examined systems: i.e. the greater the concentration of norcantharidin
      in the reaction, the greater the inhibition of NAT activities. This report is the
      first to show that norcantharidin has an inhibitory effect on NAT activity in
      HepG2 cell.

PMID- 11321476
TI  - Protective effect of phenolic compounds isolated from the hooks and stems of
      Uncaria sinensis on glutamate-induced neuronal death.
AB  - We isolated the phenolic compounds epicatechin, catechin, procyanidin B-1,
      procyanidin B-2, hyperin and caffeic acid from the hooks and stems of Uncaria
      sinensis (HSUS), and studied their protective effects against glutamate-induced
      neuronal death in cultured rat cerebellar granule cells. Cell viability evaluated
      by MTT assay was significantly increased by application of epicatechin (100-300
      microM), catechin (300 microM), procyanidin B-1 (30-300 microM) and procyanidin B
      2 (100-300 microM) compared with exposure to glutamate only. 45Ca2+ influx into
      cells induced by glutamate was also significantly inhibited by administration
      ofepicatechin (300 microM), catechin (300 microM), procyanidin B-1 (100-300
      microM) and procyanidin B-2 (100-300 microM). These results suggest that
      epicatechin, catechin, procyanidin B-1 and procyanidin B-2 are the active
      components of HSUS that protect against glutamate-induced neuronal death in
      cultured cerebellar granule cells by inhibition of Ca2+ influx.

PMID- 11321477
TI  - Epilepsy in Chinese culture.
AB  - This article reviewed the meaning and development of epilepsy in Chinese culture.
      The theories of Yin and Yang and the five elements, fundamentals of traditional
      Chinese medicine, were introduced, which form the context of understanding of the
      etiology, classification, and treatment of epilepsy in traditional Chinese
      medicine.

PMID- 11321478
TI  - Spatio-temporal pattern of EEG in young brain respiration-training children.
AB  - We have evaluated the effect of 'Brain Respiration' training on brain activity
      using Karhunen-Loeve (KL) decomposition as a method for spatio-temporal analysis
      of the electroencephalogram (EEG). BR training is a form of breath-work to
      optimize the function of the brain by concentrating Qi energy in the brain.
      Recently, BR-training has been reported to improve emotional maturity (i.e., EQ),
      short-term memory and intuition (Yoo et al., 1998). EEG data were taken during BR
      training from 12 young BR-trainees (average age: 9.4 years) who had trained for 4
      to 14 months, and during relaxation from age matched non-trained children. Spatio
      temporal analysis showed a significant difference of EEG dynamics in right
      prefrontal, right inferior frontal, posterior temporal, parietal and occipital
      areas between BR-trainees and the control group. Amplitude of eigenvector
      components of BR-trainees in the areas of frontal, temporal and occipital cortex
      was larger than that of non-trained children (values were smaller in parietal
      cortex), with remarkably high amplitude alpha coherence all over the scalp. These
      results suggest that BR-training possibly activates brain function through
      changes in the activity of the frontal association area where higher mental
      integration and creative activities are mediated.

PMID- 11321479
TI  - Moxibustion treatment of breech presentation.
AB  - Breech presentation was successfully corrected by stimulating acupuncture points
      with moxibustion or low-frequency electrical current. Only patients with breech
      pregnancies at the 28th week or later were entered into the study. With
      moxibustion treatment, the control group had a spontaneous correction rate of
      165/224 (73.66%), and the treatment group had a correction rate of 123/133
      (92.48%) (P<0.0001, x2 test). With low-frequency percutaneous electrical
      stimulation, the correction rate was 20/941 (83.87%) in the control group and
      171/191 (89.52%) in the treatment group (P=0.094, x2 test). The controls in the
      moxibustion study did no exercises and received no external manipulation to
      correct breech presentation whereas those in the electrical stimulation study
      experienced both. Acupuncture stimulation, especially with moxibustion, is
      expected to serve as a safe and effective modality in the management of breech
      presentation in a clinical setting.

PMID- 11321480
TI  - Effects of a 10-minute back rub on cardiovascular responses in healthy subjects.
AB  - This study determined the cardiovascular responses to a 10-minute back rub.
      Twelve healthy, college-age males and females (mean age = 22 years) volunteered
      to participate as subjects. Using an ABA design, the subjects tested for 10
      minutes (Control #1) on a padded plinth lying on one side. During the Treatment
      period, the back rub was administered, which was followed by Control #2. Oxygen
      consumption (VO2) was determined via the Medical Graphics CPX/D metabolic
      analyzer, which also estimated cardiac output (Q) using the CO2 rebreathing
      (equilibrium) method. A repeated measures ANOVA was performed to statistically
      compare the cardiovascular responses across the three periods. The back rub, when
      compared to Control #1, had no significant effect on VO2, but the central and
      peripheral components of VO2 were changed. Cardiac output was decreased as a
      result of the decreased stroke volume (SV), as a function of the increased
      peripheral vascular resistance (PVR). We also found an increase in the extraction
      of oxygen (a-vO2 diff) in the peripheral tissues. These results indicate that the
      VO2 response during the back rub was achieved by reciprocal central (SV,Q) and
      peripheral (a-vO2 diff) adjustments. Following the back rub, (i.e., Control #2
      vs. Treatment), the decrease in VO2, VCO2, Ve, and a-vO2 diff appears to indicate
      that it was effective in inducing relaxation. Since HR, SV, and Q were unchanged,
      the VO2 response was a result of the decreased a-vO2 diff. Hence, the findings
      suggest certain positive implications for the health care industry.

PMID- 11321481
TI  - Studies on the psychosomatic functioning of ill-health according to Eastern and
      Western medicine 5. Psychosomatic characteristics of anxiety and anxiety
      affinitive constitution.
AB  - In successive studies of the psychosomatic functioning of ill-health according to
      Oriental and Western medicine in medical students, we established the existence
      of the psychosomatic characteristics we have provisionally termed the anxiety
      affinitve constitution at the core of ill-health. Therefore, we conducted this
      research because our previous investigation showed this constitution included a
      high complexity of respiratory movement and eye movement with a significant
      correlation to the State Trait Anxiety Inventory (STAI). We examined the
      correlation between the STAI and somatic function of 88 medical students to
      identify the psychosomatic characteristics of anxiety and the anxiety-affinitive
      constitution. These tests included STAI, fractal (EEG, EOG, plethysmogram,
      respiratory curves, and EMG) and non-fractal (accelerated plethysmogram)
      dimension analyses, and malocclusion (based on Angle's classification). In
      particular, EOG, plethysmogram, and respiratory curves are known to have close
      association with trait anxiety. We were able to discover the correlation between
      (1) trait anxiety and thoracic and abdominal respiratory movements, and
      malocclusion (Class III), and (2) the correlation of state anxiety with thoracic
      respiratory movement, horizontal eye movement, a plethysmogram and an EEG-Pz (in
      males only). In subsequent study the relation between thoracic dominance and
      state-trait anxiety and between abdominal dominance and state-trait anxiety
      should be assessed to develop this research regarding the psychosomatic
      characteristics of anxiety and the anxiety-affinitive constitution. Further, it
      is essential to create an anxiety-affinitve constitution index based on multi
      regression analysis.

PMID- 11321482
TI  - Anti-HIV activity of medicinal herbs: usage and potential development.
AB  - The acquired immunodeficiency syndrome (AIDS) is a result of human
      immunodeficiency virus (HIV) infection which subsequently leads to significant
      suppression of immune functions. AIDS is a significant threat to the health of
      mankind, and the search for effective therapies to treat AIDS is of paramount
      importance. Several chemical anti-HIV agents have been developed. However,
      besides the high cost, there are adverse effects and limitations associated with
      using chemotherapy for the treatment of HIV infection. Thus, herbal medicines
      have frequently been used as an alternative medical therapy by HIV positive
      individuals and AIDS patients. The aim of this review is to summarize research
      findings for herbal medicines, which are endowed with the ability to inhibit HIV.
      In this article, we will emphasize a Chinese herbal medicine, Scutellaria
      baicalensis Georgi and its identified components (i.e., baicalein and baicalin),
      which have been shown to inhibit infectivity and replication of HIV. Potential
      development of anti-AIDS compounds using molecular modeling methods will also be
      discussed.

PMID- 11321483
TI  - Effects of Choto-san on microcirculation, serum nitric oxide and lipid peroxides
      in patients with asymptomatic cerebral infarction.
AB  - The effects of Choto-san on microcirculation, serum nitric oxide and lipid
      peroxides were investigated. Fifteen patients with asymptomatic cerebral
      infarction were investigated before and after a four-week administration of Choto
      san. The variables of microcirculation of the bulbar conjunctiva, which were the
      internal diameter of vessels, flow velocity and flow volume rate, were increased.
      Serum NO2(-)/NO3(-) tended to increase and lipid peroxides were decreased. Total
      serum cholesterol was also decreased. These results suggest that Choto-san may
      improve microcirculation affected by endothelial function and fat metabolism.

PMID- 11321484
TI  - Effect of CDA-II, urinary preparation, on lipofuscin, lipid peroxidation and
      antioxidant systems in young and middle-aged rat brain.
AB  - The levels of lipofuscin and lipid peroxidation reflect the degree of free
      radical-induced oxidative damage in the brain. We examined the effects of CDA-II,
      a preparation of human urine, on lipofuscin and lipid peroxidation in the brain
      of young (3.5 months) and middle-aged rats (17 months). The rats were given CDA
      II orally at dosages of 0.3 or 1.0 g/kg daily for 8 weeks. CDA-II significantly
      suppressed the contents of lipofuscin and lipid peroxidation in both young and
      middle-aged rats. CDA-II also elevated the activity of superoxide dismutase, and
      the amounts of glutathione and ascorbic acid in the middle-aged rats, but not in
      the young ones. Our results suggest that the protection against oxidative damage
      by CDA-II in the young rat brain may be due to its scavenging activity against
      free radicals. In the middle-aged rats, in addition to the scavenging activity,
      the levels of endogenous antioxidants were also enhanced by the CDA-II treatment.

PMID- 11321485
TI  - Recurrent Paget's disease of the vulva in a myocutaneous flap: case report and
      review of the literature.
AB  - A 74-year-old patient with recurrent Paget's disease of the vulva in the gluteus
      maximus island myocutaneous flap 11 years after a hemivulvectomy with
      reconstruction is presented. This report is only the second case of recurrent
      noninvasive Paget's disease in a reconstructive flap. The English literature on
      this subject is reviewed with special attention to the biological behavior of
      these tumors.

PMID- 11321486
TI  - 60Cobalt vs. linear accelerator in the treatment of locally advanced cervix
      carcinoma: a comparison of survival and recurrence patterns.
AB  - OBJECTIVE: To compare the survival and recurrence patterns of patients with
      locally advanced cervical carcinoma treated with 60cobalt radiotherapy units and
      linear accelerators. METHODS: Two hundred and forty-eight patients with cervical
      carcinoma stages IIB-IVA who were treated with primary irradiation between the
      years 1985 and 1988 comprised the study group. The median survival of patients
      treated with 60cobalt units and linear accelerators was calculated using the
      method of Kaplan and Meier and compared using the log-rank test. Recurrence
      patterns were compared using chi-square analysis; p < .05 was considered
      significant for all tests. RESULTS: One hundred and ninety-five patients were
      treated with 60cobalt units (Group 1) and 53 patients were treated with a linear
      accelerator (Group 2). Group 1 and 2 were similar with regard to mean age and
      weight, stage distribution, and mean dose to point A. The rate of recurrence was
      comparable between Group 1 and 2 (65.6% vs. 64.2%) and no significant difference
      was found in overall survival between the groups (20 months vs. 21 months. p =
      81). There was a trend toward increasing pelvic recurrence in Group 1 (50.8%)
      compared to Group 2 (35.8%, p = .08). CONCLUSIONS: 60Cobalt units and linear
      accelerators offer comparable rates of overall survival in patients with locally
      advanced cervix carcinoma.

PMID- 11321487
TI  - Primary vaginal melanoma and long-term survivors.
AB  - Vaginal melanoma is a rare and highly malignant disease. This report describes
      the characteristics and clinical course of all patients treated at one institute
      (Northern Gynaecological Oncology Centre, UK) over the last 25 years. Of a total
      of nine patients identified with a primary malignant vaginal melanoma, only one
      patient survived for more than five years. A literature review revealed only 21
      reported cases with a survival greater than five years. The most important factor
      for survival appears to be the tumour size. Treatment modality varied equally
      within the group of long-term survivors (27% radical surgery, 27% wide local
      excision, 27% radiotherapy, 14% wide local excision and radiotherapy, and 5%
      unknown therapy). The prognosis of patients with primary malignant melanoma is
      poor, regardless of primary therapy (conservative or radical). Conservative
      treatment and accurate investigation of every discoloured lesion is recommended.

PMID- 11321489
TI  - Prevalence and management of (non-fistulous) urinary incontinence in women
      following radical hysterectomy for early stage cervical cancer.
AB  - OBJECTIVES: 1) to determine the prevalence of urinary incontinence before and
      after radical surgical treatment for early cervical cancer, 2) to retrospectively
      analyse the outcome results following the investigation/treatment of incontinence
      in these women. PATIENTS AND METHODS: 27 women were studied prospectively by
      questionnaire prior to surgery and six weeks and three months after surgery
      (group 1). Seventy-seven women who were more than 12 months post-radical surgery
      were questioned directly at the follow-up clinic (group 2). Three hundred and two
      satisfactory responses were obtained to questionnaires sent to general
      practitioners of patients previously treated by radical surgery for early
      cervical cancer (group 3). RESULTS: 14.8% of women reported regular incontinence
      prior to surgery, and 48.1% and 29.6% of women, respectively, reported regular
      incontinence six weeks and three months after surgery; 31.2% of women also
      reported regular incontinence more than 12 months after post-radical surgery. Of
      the women in the 12-month post-radical surgery group, 16.6% had considered their
      symptoms of regular incontinence severe enough to attend their local practice for
      treatment and 14.6% (44 women) were referred for further management. In six of
      these 44 patients (13.6%), spontaneous resolution of incontinence occurred at
      varying intervals within the first 12 months following radical surgery. Twenty
      four of the 44 women who were referred underwent urodynamic investigation. Of
      these 24 women, in 17 cases the diagnosis was genuine stress incontinence (GSI),
      of which, in seven cases (41%) GSI was the sole urodynamic abnormality. In six of
      these seven cases (85.7%), the women were cured or very greatly improved
      following treatment with either physiotherapy or surgery. However, only six of
      the remaining ten cases (60%) with coexistent abnormalities achieved this result.
      Patients with coexistent impaired bladder compliance showed the poorest result,
      as only two of the six cases (33%) achieved satisfactory improvement following
      treatment. CONCLUSION: Non-fistulous urinary incontinence following radical
      pelvic surgery for carcinoma of the cervix despite being a common problem shows a
      significant spontaneous improvement rate within the first 12 months following
      surgery. Urodynamics should be a mandatory investigation in patients who complain
      of persisting problems thereafter. Subjective improvement rates for women with
      genuine stress incontinence alone are in excess of 85%, being comparable to those
      of women without any prior history of radical pelvic surgery.

PMID- 11321488
TI  - Detection of numerical aberration in chromosome 17 and c-erbB2 gene amplification
      in epithelial ovarian cancer using recently established dual color FISH.
AB  - This paper presents a new dual color FISH technique that will allow the use of
      cell specimens isolated from formaldehyde-fixed and paraffin-embedded (F-P)
      tissues. The new FISH method was used to examine numerical aberration in
      chromosome 17 and c-erbB2 gene amplification in 26 F-P epithelial ovarian cancer
      tissues. Numerical aberration of chromosome 17 appears frequently in clear cell
      adenocarcinoma. The frequency of amplification of the c-erbB2 gene in stage III
      and IV cases was significantly higher than in stage I cases. The FISH technique
      as established here may serve as a molecular tool for examination of clinico
      pathological significance in F-P tissues.

PMID- 11321490
TI  - Radical vaginal hysterectomy with extraperitoneal pelvic lymphadenectomy in
      cervical cancer.
AB  - OBJECTIVE: The aim of this work was to examine three types of radical vaginal
      hysterectomy with different degrees of radicality, performed in order to reduce
      surgical complications and sequelae in different indications, and to test the
      feasibility of a new simple and quick technique for extraperitoneal pelvic
      lymphadenectomy to be used in combination with radical vaginal hysterectomy for
      treatment of cervical cancer. In this way the advantages of vaginal surgery
      (e.g.: unnecessary general anaesthesia, reduced surgical trauma, applicability to
      obese and poor surgical risk patients, fast time-saving procedure) can be
      preserved. METHODS: We compared retrospectively the long-term results of radical
      vaginal and radical abdominal operations in a large series of stage IB-IIA
      cervical cancer patients treated at our institution in Florence from 1968 to
      1983. Furthermore, we analysed the results of our experience from 1995 to 1998,
      when we performed extraperitoneal pelvic lymphadenectomy, followed by radical
      vaginal hysterectomy, on 48 patients affected by cervical cancer. Extraperitoneal
      pelvic lymphadenectomy was performed through two small abdominal incisions (6-7
      cm). Twenty-two patients (45%) were obese (BMI>30 kg/m2) and 20 were poor
      surgical risks. FIGO stage was: IB1 in 18 cases, IB2 in eight, IIA in six, IIB in
      12, IIIB in four. Neoadjuvant chemotherapy was given in 12 cases and preoperative
      irradiation was given in ten. General and regional anaesthesia were used in 30
      (62.5%) and in 18 (37.5%) cases, respectively. RESULTS: As for past experience,
      in stage IB the five-year survival of 356 patients who underwent radical vaginal
      hysterectomy and that of 288 who had radical abdominal hysterectomy with pelvic
      lymphadenectomy were 81% and 75%, respectively (p<0.05). Surgical complications
      were fewer with no mortality in the first group. In stage IIA, survival rates
      were 68% for radical vaginal hysterectomy and 64% for radical abdominal
      hysterectomy, in 76 and 64 cases, respectively (p=n.s.). As for the more recent
      experience, median operative time for extraperitoneal pelvic lymphadenectomy was
      20 minutes for each side (range 15-36). In each patient a median of 26 lymph
      nodes were removed (range 16-48). Positive nodes were found in 12 cases (25%).
      Median operative time for radical vaginal hysterectomy was 40 minutes (range 30
      65). Extraperitoneal pelvic lymphadenectomy complications included: lymphocyst,
      five cases (10%) and retroperitoneal hematoma, one (2%); all occurred at the
      beginning of the experience. Radical vaginal hysterectomy complications included:
      ureteral stenosis, one (2%) and uretero-vaginal fistula, one (2%). All
      complications occurred in patients who received radiotherapy or chemotherapy
      preoperatively. Median hospital stay was ten days (range 6-20). CONCLUSIONS: The
      results of our work demonstrate that our technique for extraperitoneal pelvic
      lymphadenectomy shows a good applicability to cervical cancer patients submitted
      to radical vaginal hysterectomy, which has a high rate of cure for stage IB and
      IIA as shown by our past experience. The procedure of extraperitoneal pelvic
      lymphadenectomy was quick, easy, and safe, and its realization was not
      detrimental to the advantages of radical vaginal hysterectomy. Our experience
      supports the continued use of this combined extraperitoneal and vaginal approach
      in the treatment of cervical cancer. Moreover, the three classes of radical
      vaginal hysterectomy allow tailoring the type of the operation to the clinical
      and physical characteristics of the patients.

PMID- 11321491
TI  - Does long-term follow-up have a role for node negative squamous carcinoma of the
      vulva? The Gateshead experience.
AB  - A retrospective review was performed of 138 cases of squamous vulval cancer
      referred to Gateshead between 1986 and 1997, with a median follow-up of 48
      months. Eighteen recurrences were detected, 11 within one year of surgery. All
      nine patients with groin/distant recurrence (including 4 presenting initially
      with local recurrence only) died of vulval cancer. Vulval pain, bleeding or other
      symptoms heralded all recurrences. Routine review was ineffective in detecting
      recurrence. Eight cases were detected by general practitioners, three by
      specialists, and one was self-diagnosed. Six of these had had clinical review
      less than two months previously. Follow-up does not appear to offer early
      detection or survival advantages. Patient education, with symptom-triggered rapid
      clinic access, may be more effective. Prospective research is indicated to assess
      both the effectiveness and psychological implications of routine follow-up and
      alternative strategies.

PMID- 11321492
TI  - Response to neo-adjuvant intraperitoneal and intravenous immunochemotherapy
      followed by interval secondary cytoreduction in stage IIIc ovarian cancer.
AB  - DESIGN: The aim of this study was to determine the effect of intraperitoneal
      (i.p.) neo-adjuvant immunochemotherapy, followed by secondary interval
      cytoreduction in bulky ovarian carcinoma, considered inoperable at first
      exploratory laparotomy. PATIENTS AND METHODS: From 1980 to 1996, 13 naive
      patients with stage IIIc ovarian cancer underwent an initial laparotomy.
      Cytoreduction was judged too dangerous in these patients due to the large bulk of
      the tumor and the extent of peritoneal carcinomatosis. Simple biopsies were
      performed. The patients received an intraperitoneal cisplatin-based protocol
      monthly plus immunotherapy (DGZ). The interval secondary cytoreduction was
      started either when the patients seemed to be in complete remission or after a
      minimum of 4 courses of chemotherapy if the patients' results were stagnant or
      deteriorated. Immunochemotherapy was then resumed for a total of up to 10
      courses. RESULTS: At secondary cytoreduction, six patients were in complete
      remission as demonstrated histologically and cytologically. Seven patients were
      in incomplete remission. In six, debulking was completed without visceral
      resection. The seventh patient still had nodules more than 2 cm in diameter.
      Median overall survival was 57 months (range: 6-165). CONCLUSION: Intraperitoneal
      immunochemotherapy was effective in bulky tumors, making optimal secondary
      cytoreduction possible in almost all cases.

PMID- 11321493
TI  - Advanced primary carcinoma of the Bartholin gland: report of 18 patients.
AB  - Conservative surgery plus radiotherapy for vulvar cancer has been established as
      a therapeutic alternative to extensive radical surgery and produces a similar
      cumulative 5-year survival. We retrospectively analyzed the cases of 18 patients
      with advanced primary carcinoma of the Bartholin gland treated with wide local
      excision (WLE) or radical vulvectomy and lymphadenectomy followed by radiotherapy
      (RT) at the University of Texas M. D. Anderson Cancer Center from January 1978
      through December 1990. All patients have been observed for a minimum of 7 months
      (maximum follow-up, 15 years; median follow-up, 9 years). Of the 18 patients, 7
      were treated with wide local excision (WLE) followed by radiation therapy (RT)
      (Group 1), 9 had radical vulvectomy (RV) followed by RT to the vulvar and
      inguinal-femoral and pelvic node areas (Group II), and 2 were treated with RT
      alone after biopsy of the tumor (Group III). The 5-year disease-free survival
      rates were 86%, 78%, and 50% for groups I, II, and III, respectively, and 83% for
      the whole group. Of 2 patients treated with RT alone, one lived for 6 years with
      no evidence of disease, and the other lived for 20 months. The rate of local
      tumor control was 100% for all three treatment groups. There were no significant
      differences among the treatment groups in rate of primary tumor control or 5-year
      disease-free survival rate (p=0.1300). The present study demonstrated WLE
      followed by RT is the best treatment for advanced primary carcinoma of the
      Bartholin gland. Less radical surgery plus RT produces good long-term survival
      and has fewer complications.

PMID- 11321494
TI  - A report of the E.S.G.O. session during the Fifth European Meeting of the French
      Society of Gynecology "Recent data about endometrial carcinoma".

PMID- 11321495
TI  - Increased expression of interleukin-1 beta is associated with persistence of the
      disease and invasion in complete hydatidiform moles (CHM).
AB  - Complete hydatidiform moles (CHM), a post-conceptual pathologic condition of the
      placenta, have a high prevalence rate (12/1,000 deliveries) in Kerala, India.
      This study addresses the expression of IL-1 alpha and beta by
      immunohistochemistry in relation to persistence and invasion of the disease. Mild
      to moderate expression of IL-1 alpha in the villous cytotrophoblasts,
      syncytiotrophoblasts and decidua of the first trimester in the normal placenta
      and all gestational ages in the molar placenta were observed. IL-1 beta
      expression was observed in the extravillous trophoblasts, syncytiotrophoblasts
      and decidua in both the normal and molar placentae and also in the villous
      cytotrophoblasts and the stromal Haufbaur cells in molar placentae. Strong
      expression of IL-1 beta in the placenta suggests its involvement in placental
      physiology supporting earlier reports. Higher expression of IL-1 beta correlated
      well with the invasive and persistent nature of the tumour and holds potential as
      a marker of persistence and invasion in CHM.

PMID- 11321496
TI  - Primary epithelial ovarian carcinoma in Taiwanese women.
AB  - PURPOSE OF INVESTIGATION: Primary epithelial ovarian carcinoma is common in
      industrial countries but rare in the Orient. In fact, it is still a rare disease
      in Taiwan. In this article, we report the general data of Taiwanese patients with
      primary epithelial ovarian carcinoma. METHODS: In this retrospective study we
      used univariate and multivariate analysis models to analyze the prognosis of
      patients with surgically confirmed primary epithelial ovarian carcinoma. One
      hundred and ninety-four patients from 1990 to 1996 were identified and enrolled
      in this study. RESULTS: The mean follow-up time was 44.7 months with an interval
      between 15.1 months and 105.9 months. Univariate analysis showed postmenopausal
      status, advanced stage, presence of lymph node metastasis, poor differentiation,
      and suboptimal surgery as risk factors for disease recurrence and subsequent
      deaths. Multivariate analysis demonstrated stage as the most important factor
      correlated with recurrent disease (risk ratio: 7.303 and 5.409, respectively),
      followed by optimal surgery (RR: 2.447), and cellular differentiation (RR:
      1.677). CONCLUSIONS: Our data on the Taiwan population were consistent with other
      reports of different races. Early detection for primary epithelial ovarian cancer
      is of great importance because stage is still the most important predictor in
      disease-free survival and disease-related deaths. Application of the most
      reliable and acceptable methods of screening is our goal in the next century
      after weighing benefits over costs.

PMID- 11321497
TI  - Fetal cells from cord blood as stem cell source: current status and possible
      implications in gynaecologic oncology.
AB  - Umbilical cord blood is increasingly used as a source of hematopoietic stem cells
      for transplantation. Due to recent success, cord blood banks are being set up. We
      reviewed the currently available literature concerning cord blood collection,
      storage and transplantation, the impact of prenatal and perinatal factors and
      collection techniques on the quantity and quality of cord blood, and the ethical,
      legal and social questions related to cord blood transplantation. Possible
      implications in gynecologic oncology are reviewed and discussed. The emerging
      therapeutic use of cord blood for transplantation and transfusion implies new
      challenges for the speciality of gynecology and obstetrics.

PMID- 11321498
TI  - Adenosarcoma of the uterine body in a 19-year-old woman--three year survival:
      case report.
AB  - BACKGROUND: Uterine adenosarcoma is a rarely by occurring tumor. It is composed
      of a benign adenoid structure and a sarcomatous stromal component. The average
      age of patients with a diagnosis of uterine adenosarcoma is about 70 years. CASE:
      We present a case of a 19-year-old woman with a rarely occurring uterine
      adenosarcoma manifesting itself by irregular bleeding and producing fragile
      polypous matter which was spreading into the vagina. The final diagnosis was made
      only by repeated biopsies. Abdominal hysterectomy with bilateral salpingo
      oophorectomy, appendectomy and revision of iliac lymph nodes were performed.
      Teleradiotherapy was applied from 4 fields in 25 fractions to a total exposure of
      50 Gy. It was followed by six cycles of chemotherapy containing 50 mg/m2
      doxorubicin and 5 g/m2 ifosfamid administered in 21-day dose intervals.
      CONCLUSION: This case should demonstrate the difficulty of making the right
      diagnosis. Since the end of therapy the patient has been regularly seen in our
      onco-gynecologic department. Now, 40 months after the end of chemotherapy and 46
      months after making the diagnosis, there are no signs of relapse.

PMID- 11321499
TI  - Microinvasive carcinoma of the cervix. Analysis of prognostic factors.
AB  - INTRODUCTION: Superficially invasive neoplasias of the uterine cervix are a
      matter of controversy in terms of their definition, prognostic factors and
      selection of treatment to minimize the risk of recurrences. We reviewed our
      treatment to determine whether any factors affect this risk. PATIENTS AND
      METHODS: The present study was conducted on 59 patients seen at our service, 22
      of them with early stromal invasion (IA1) and 37 with microinvasive carcinoma
      (IA2) according to FIGO criteria (1995). Ten patients were submitted to
      conization as definitive treatment, although for three of them treatment was
      complemented with Wertheim-Meigs surgery due to recurrence in the remaining
      cervix. The other 49 patients were submitted to total abdominal hysterectomy.
      RESULTS: Forty-four patients underwent diagnostic or therapeutic conization, and
      14 of them presented involvement of the endocervical margin. Seven patients
      presented recurrence with involvement of the endocervical margin in five. The age
      of recurrence ranged from 40 to 70 years, with a mean of 52.3 years, as opposed
      to a general mean of 42.3 (p<0.05). Angiolymphatic invasion was positively
      correlated to recurrence and death (p<0.01) as well as depth of invasion.
      CONCLUSIONS: We conclude that the presence of a cone with an involved
      endocervical margin represents a high risk of recurrence and that this condition
      occurs in older patients who are prone to present more extensive lesions. Thus,
      age should be regarded as an important risk factor. Angiolymphatic invasion and
      depth of invasion have a poor prognosis in terms of recurrence and death.

PMID- 11321500
TI  - Malignant mixed mullerian tumor of the ovary: report of four cases.
AB  - INTRODUCTION: Malignant mixed mullerian tumor (MMMT) of the ovary is an extremely
      rare gynaecologic neoplasm that represents 1% of the malignances of this organ.
      Stage I disease is rare because it is asymptomatic in early stage. We describe
      four cases. CASE REPORTS: In the Department of Obstetrics and Gynecology of the
      University of Bari four cases of MMMT of the ovary were diagnosed. Three patients
      were in stage IIIC and one of them was a homologous MMMT; the fourth patient was
      affected by a heterologous stage IV MMMT. All women were treated with surgery and
      chemotherapy. Two patients are alive 14 and 12 months after diagnosis. The other
      two died after 37 months and one month, respectively. CONCLUSIONS: The malignant
      mixed mullerian tumor (MMMT) of the ovary is a particularly aggressive tumor,
      especially in advanced stages. The survival rate is very low in spite of surgery,
      chemotherapy and radiotherapy. The optimal treatment for this neoplasm is unknown
      because of its rarity. Our experience, when considering survival, seems to
      confirm the use of cisplatin and ifosfamide and to give new horizons to taxol.

PMID- 11321501
TI  - The efficacy of combination chemotherapy including intraperitoneal cisplatinum
      and mitoxantrone with intravenous ifosfamide in patients with FIGO stage I C
      ovarian carcinoma.
AB  - OBJECTIVE: Patients with stage I ovarian cancer show a high incidence of
      recurrent disease ranging from 30% to 50%, which may be associated with a
      shortened survival. Therefore, a subset of early-stage patients with poor
      prognostic factors who are most likely to present with recurrent disease in the
      next few years may benefit from adjuvant treatment. PATIENTS AND METHOD: In this
      pilot study, we evaluated the efficacy of combination chemotherapy including
      intraperitoneal mitoxantrone (12 mg/ml) and cisplatinum (75 mg/ml) on day 1, in
      addition to intravenous ifosfamide (4000 mg/m2) given on day 15 with mesna
      protection. Thirteen patients with a median age of 44 years were included in the
      study. RESULTS: Following a median of 5 cycles of chemotherapy, 12 patients had a
      complete response (92.3%), while one patient had progressive disease. At the
      latest follow-up, ten patients were alive with no evidence of disease, two
      patients had died and one patient was lost to follow-up. Overall and progression
      free survival rates at eight years were 82.5+/-11.3% and 83.9+/-10.5%,
      respectively. Excluding grade 3 and 4 abdominal pain in three (23.1%) patients,
      there were no serious complications associated with this combination. Dose delay
      not longer than one week was observed in 3 cycles (5.6%). Port-related
      complications observed in three patients were colonic perforation, hematoma and
      leakage. CONCLUSION: This combination has moderate efficacy and tolerable
      toxicity. However, further studies are required to make definite conclusions
      regarding the efficacy of this combination in the adjuvant setting in patients
      with high-risk early stage ovarian carcinoma.

PMID- 11321502
TI  - Tailgut cysts: a rare cause of pelvic outlet obstruction.
AB  - Tailgut cysts are unusual cystic tumors of the retrorectal space. We describe the
      findings of three cases. Constipation, intrapelvic fullness and low abdominal
      pain were the most prominent clinical manifestations. One patient developed an
      abscess. Ultrasound, computed tomography and MR imaging demonstrated the
      presacral lesions. Transabdominal excision of the tumors in two patients resulted
      in good outcome whereas in the patient with the abscess there was recurrence with
      a fistula formation.

PMID- 11321503
TI  - Preliminary experience with Mainz type II pouch in gynecologic oncology patients.
AB  - OBJECTIVE: To evaluate the Mainz low-pressure modification of
      ureterosigmoidostomy with extramural serous-lined ureterointestinal anastomosis
      as a method of urinary diversion in gynecologic patients undergoing anterior
      pelvic exenteration. MATERIALS & METHODS: Between December 1995 and September
      1998, Mainz type II pouch was performed in 11 patients aged between 27-70 years
      (mean 58.5). Four were diagnosed with cervical cancer (2 stage IV A and 2 central
      recurrences following radical hysterectomy done elsewhere), two with stage III
      bilharzial bladder cancer, two with urethral cancer (one stage III and one
      recurrent following surgery done elsewhere), one with stage IV A endometrial
      cancer, one with stage IV A vaginal cancer complicating long standing
      incarcerated total procidentia and lastly one patient with refractory obstetric
      vesicovaginal fistula with almost total loss of the upper urethra, bladder neck
      and base. All patients were followed closely and particular complications related
      to the diversion were recorded as acid-base imbalance, renal impairment and
      incontinence. RESULTS: The pouch construction with anterior exenteration took an
      average of 242 min (150-330). There were two postoperative deaths due to
      pulmonary embolism and pneumonia both being related to the precarious condition
      of the patients and not to the diversionary procedure. The follow-up ranged
      between 25-60 months, with a mean of 43.5 months for the surviving patients.
      During that time period, four deaths occurred due to cancer recurrence.
      Otherwise, all patients remained continent during the day with one patient being
      incontinent at night. Two patients developed one attack of pyelonephritis and
      were treated successfully with antibiotics. No hyperchloremic acidosis and no
      hydronephrotic changes were seen in any patient and renal function remained
      normal. CONCLUSION: Mainz type II pouch with extramural serous-lined
      ureterointestinal anastomosis is a safe promising quick and easy method of
      urinary diversion for patients undergoing anterior pelvic exenteration and having
      an intact anal sphincter. Longer follow-up and a greater number of patients will
      be needed to compare it with other forms of urinary diversion.

PMID- 11321504
TI  - Side-effects of paclitaxel therapy in ovarian cancer patents.
AB  - OBJECTIVE: Since premedication with H1, H2 receptor antagonists and steroids
      fewer side-effects of paclitaxel (PTXL) chemotherapy have been published. The
      authors summarize the literature and their own experience. MATERIALS AND METHODS:
      23 patients with stage III ovarian cancer were treated with second-line
      chemotherapy of PTXL and carboplatin (CRB) with the doses of 175 mg/m2, 3 h and
      AUC 5 mg/ml x min, respectively. The side-effects of treatment are evaluated in a
      prospective non-randomized study. RESULTS: Rare toxicity in hemoglobin (G0-15%,
      G1-62%, G2-12% and G4-4%) and leukocyte levels (G0-35%, G1-25%, G2-29%, G3-11%
      and G4-0%) were detected. There was no definite change found in platelet count
      (G0-89.5%, G1-10.5%), and moreover in 15.8% of the patients the controlled
      platelet count was higher than the normal laboratory range. Liver enzymes, serum
      creatinine and carbamide levels in each case were within the normal range (G0).
      One patient complained of severe neuropathy (nervus oculomotorius paresis), and
      another one developed severe ECG abnormalities CONCLUSIONS: When suitable
      premedication is applied few side-effects of PTXL therapy are reported.

PMID- 11321505
TI  - Involvement of cyclooxygenase-derived prostaglandin E2 and nitric oxide in the
      protection of rat pancreas afforded by low dose of lipopolysaccharide.
AB  - Prostaglandins (PG), the products of arachidonate metabolism through
      cyclooxygenase (COX) pathway, protect the pancreas from the acute damage. The
      existence of two isoforms of COX was documented including: COX-1, present in
      normal tissues and COX-2, expressed at the site of inflammation, such as induced
      by bacterial lipopolysaccharide (LPS). Pretreatment with low dose of LPS and
      activation of nitric oxide (NO) synthase (NOS) has been shown to prevent the
      injury caused by caerulein-induced pancreatitis (CIP) in the rat. The aim of this
      study was to investigate the role of COX-1 and COX-2 in the LPS-induced
      protection of the pancreas against CIP and the involvement of NOS in the
      activation of COX-PG system in the rats with CIP. CIP was produced by
      subcutaneous (s.c.) infusion of caerulein (5 microg/kg-h for 5 h) to the
      conscious rats. Protective dose of LPS, from Escherichia coli, (1 mg/kg) was
      given intraperitoneally (i.p.) 15 min prior to the start of CIP. Nonselective
      inhibitor of COX; indomethacin (5 or 10 mg/kg), selective inhibitor of COX-1:
      resveratrol, or a highly selective inhibitors of COX-2: rofecoxib or NS-398 (2 or
      10 mg/kg) were injected i.p. 15 min prior to the administration of LPS. COX-1 or
      COX-2 mRNA was determined by reverse transcription-polimerase chain reaction (RT
      PCR) in the pancreatic tissue. Pancreatic blood flow (PBF) was measured by a
      laser Doppler flowmetry. PGE2 content in the pancreas was measured by
      radioimmunoassay. CIP was manifested by an increase of pancreatic weight and
      plasma amylase activity (by 500% and 700%, respectively) and it was confirmed by
      histological examination. CIP slightly increased pancreatic PGE2 generation (by
      12%) and diminished PBF (by about 40%). LPS (1 mg/kg i.p.), given prior to the
      start of CIP, increased PGE2 generation in the pancreas (by 45%), reversed the
      histological manifestations of pancreatitis, reduced the rise in amylase blood
      level and improved PBF. Administration of nonselective inhibitor of COX;
      indomethacin (5 or 10 mg/kg i.p.) prior to the injection of LPS abolished its
      protective effects on CIP and reduced pancreatic PGE2 generation. Selective
      inhibitor of COX-1; resveratrol (10 mg/kg i.p.) given prior to the injection of
      LPS reversed its protective effects against CIP. Pretreatment with a selective
      inhibitors of COX-2: rofecoxib or NS-398 (10 mg/kg) attenuated LPS-induced
      pancreatic protection in the CIP rats. COX-1 expression was detected in the
      intact pancreas and was not significantly changed by CIP, LPS, indomethacin, NS
      389 and their combination, while COX-2 mRNA expression appeared in the pancreas
      of ratssubjected to CIP and was significantly increased after LPS injection to
      these rats. Addition of selective COX-2 inhibitor; NS-389, or nonselective
      inhibitor of COX; indomethacin, enhanced COX-2 mRNA expression in the rats with
      CIP pretreated with LPS. Pretreatment of the rats with inhibitor of NOS; L-NNA
      (20 mg/kg i.p.), given together with LPS, 15 min prior to the start of caerulein
      overstimulation, resulted in complete reversion of LPS-induced pancreatic
      protection and decreased PGE2 generation stimulated by LPS. Addition to L-NNA of
      the substrate for NOS; L-arginine (100 mg/kg i.p.), restored pancreatic
      protection afforded by low dose of LPS and increased pancreatic PGE2 level in the
      rats with CIP. We conclude that: 1. increased pancreatic PGE2 generation, induced
      by low dose LPS pretreatment, contributes to the pancreatic resistance to acute
      damage produced by caerulein overstimulation and 2. the NO-system is involved in
      above stimulation of PGE2 generation and pancreatic protection against acute
      damage.

PMID- 11321506
TI  - Actions of several substituted short analogues of porcine galanin on isolated rat
      fundus strips: a structure-activity relationship.
AB  - The activity of porcine galanin (Gal) fragments and analogues were tested in
      vitro using rat gastric fundus strips. The peptides contracted longitudinal
      smooth muscle in a concentration-dependent manner with the following order of
      potency: [Nle4]Gal(1-15), Gal(-15), [Cle4]Gal(1-15), [Hse6]Gal(1-15), [Va14]Gal(1
      15), [Ile4]Gal(1-15), [endoTrip2a, Cle4]Gal(1-15), [desThr3, Cle4]Gal(1-15), [D
      Leu4] Gal(1-15), [desLeu4]Gal(1-15). On the contrary [desTrp2, Val4]Gal (1-15)
      remained inactive up to 10 microM. The values of Hill's coefficients estimated
      from the appropriate concentration-contraction curves for all analogues except
      for [Val4]Gal(1-15), [Hse6]Gal(1-15), [endoTrp2a,Cle4]Gal(1-15), [desLeu4]Gal(1
      15) and [D-Leu4] Gal(1-15) did not significantly differ from unity. Our results
      indicate that the integrity of the first four N-terminal amino acids of Gal
      molecule is essential for the full excitatory myogenic action of the peptide in
      rat gastric fundus. Similarly, substitution, addition or deletion of amino acid
      residues in positions two, three, four and six can considerably influence the
      ability of Gal analogues to interact with Gal receptors. The data acquired in the
      course of our structure-activity study suggest that both N- and C-terminals of
      Gal molecule contribute towards the affinity and activity of Gal in rat gastric
      smooth muscle cell receptors.

PMID- 11321507
TI  - Fucoidan improves the renal blood flow in the early stage of renal
      ischemia/reperfusion injury in the rat.
AB  - It has been shown that monoclonal anti-P-selectin antibody administration
      protects renal function in an ischemic model of acute renal failure. This study
      was designed to evaluate the effect of administration of fucoidan, P-selectin
      inhibitor, on reduction in renal blood flow induced by ischemia/reperfusion
      injury in the rat. Experiments were performed on male Wistar rats weighting 35
      400 g. The systemic blood pressure (mm Hg) (BP) and renal blood flow (RBF) were
      monitored continuously and renal vascular resistance (RVR) was calculated. After
      20 min period of stabilization animals (6 rats in each group) received one of the
      following agents administered by continuous i.v. infusion during 165 min: 1 mg/kg
      of body weight of fucoidan (F1), 10 mg/kg of fucoidan (F10), 100 mg/kg of
      fucoidan (F100), 10 mg/kg of heparin (H), or 0.9% NaCl solution (control). After
      15 min of drug administration the renal vessels of the both kidney were occluded
      with vascular clamps for 60 min. There were no significant changes in the initial
      values of RBF, RVR and BP between groups. None procedure affected significantly
      BP during all experiments. In F10 RBF returned to the initial values in 70th min
      of reperfusion and did not change up to 90th min. This value was significantly
      higher than respective value in the control group. In F1 group RBF in 90th min
      was also higher than in the control group, but it was not statistically
      significant. The dose of heparine and fucoidan used in the H and F100 groups
      failed to preserve RBF during reperfusion. In the present study we found that
      administration of fucoidan--P-selectin inhibitor, increases significantly
      postischemic renal blood flow and may have renoprotective activity.

PMID- 11321508
TI  - Studies on the effects of lipopolysaccharide on lipid peroxidation of erythrocyte
      and its reversal by mannitol and glycerol.
AB  - Gram-negative sepsis often produces endotoxin (LPS) which causes infection.
      Reduction in tissue perfusion due to microcirculatory failure may lead to septic
      shock. We studied the effect of LPS on lipid peroxidation of erythrocyte. In
      vitro studies using 50 microg to 250 microg LPS/ml blood showed increased lipid
      peroxidation of erythrocyte in a dose-dependent manner. The increased effect of
      lipid peroxidation does not occur with LPS when erythrocytes were washed to
      remove plasma and leukocytes. Mannitol and glycerol, known scavengers of hydroxyl
      radical, arrest the elevation in lipid peroxidation of erythrocytes after LPS
      treatment. Hemolysis of erythrocytes was reduced with low doses of LPS. Plasma
      lipid peroxidation was elevated after treatment of blood with LPS. From the
      results we suggest that the peroxidation of erythrocyte lipid caused by LPS may
      probably play a role in the production of septic shock.

PMID- 11321509
TI  - Heat  shock protein 70 (HSP70) in gastric adaptation to aspirin in Helicobacter
      pylori infection.
AB  - We have recently shown that adaptation of gastric mucosa to aspirin (ASA) is
      disturbed in Helicobacter pylori (H. pylori)-infected human stomach, but can be
      restored by eradication of the bacterium. The aim of this study was 1) to
      evaluate the influence of H. pylori on expression of heat shock protein 70
      (HSP70) during ASA ingestion in these subjects and in mice model and 2) to
      evaluate, whether altered HSP70 expression might be associated with different
      adaptation to ASA in H. pylori-positive and eradicated subjects. The gastric
      mucosal HSP 70 gene expression was determined by quantitative RT-PCR and Western
      blot and immunohistochemistry during 14 days of ASA ingestion (1 g bid) in the
      same 8 subjects before and 3 months after successful eradication of H. pylori. In
      addition, HSP70 mRNA and protein expression were examined in 30 mice without and
      with H. pylori infection and eradication. During 14 days of ASA treatment, human
      H. pylori-infected mucosa revealed a decrease of HSP70 expression, while after
      eradication a higher expression and further increase of HSP70 expression during
      ASA ingestion were observed. Mice inoculated with H. pylori also exhibited
      decreased gastric mucosal HSP70 mRNA expression that was restored after
      eradication therapy. Decreased basal and ASA-induced expression of HSP70 may
      partly be responsible for impaired gastric adaptation to ASA in H. pylori
      positive subjects. We conclude that 1. The HSP70 gene and protein expression is
      reduced during infection with H. pylori in men and mice and that gastric
      adaptation to ASA in H. pylori eradicated subjects is accompanied by increased
      HSP70 expression; 2. It is reasonable to assume that decreased HSP70 expression
      might contribute to disturbed gastric adaptation in H. pylori infection in humans
      and 3. The expression of HSP70 plays an important role in the mechanism of
      gastric adaptation to ASA and that H. pylori infection interferes with this
      adaptation due to decrease of HSP70 expression in gastric mucosal cells.

PMID- 11321510
TI  - Vascular changes in cyclosporine A-induced hypertension and nephrotoxicity in
      spontaneously hypertensive rats on high-sodium diet.
AB  - Functional and morphological changes of blood vessels in cyclosporine A (CsA)
      induced hypertension and nephrotoxicity were studied in spontaneously
      hypertensive rats (SHR). The role of the L-arginine-nitric oxide (NO) pathway and
      the importance of oxidative stress in CsA toxicity were also assessed. SHR (7-8
      week old) on a high-sodium diet were treated with CsA (5 mg kg(-1) d(-1) s.c.)
      for 6 weeks. A proportion of the rats were treated concomitantly with the NO
      precursor L-arginine (1.7 g kg(-1)d(-1) p.o.). CsA elevated blood pressure and
      caused renal dysfunction and morphological nephrotoxicity. CsA also impaired
      mesenteric and renal arterial function and caused structural damage to intrarenal
      and extrarenal small arteries and arterioles. Medial atrophy of the mesenteric
      resistance vessels and decreased viability of smooth muscle cells of the thoracic
      aorta were observed. Renal and arterial damage was associated with the presence
      of inflammatory cells. CsA did not affect markers of the L-arginine-NO pathway
      (urinary cyclic GMP excretion or endothelial or inducible NO synthase expression
      in kidney, aorta or heart) or oxidative stress (urinary excretion of 8
      isoprostaglandin F2alpha, plasma urate concentration or total radical trapping
      capacity). Concomitant L-arginine treatment did not affect CsA-induced changes in
      blood pressure or histological findings but tended to alleviate the arterial
      dysfunction. The renal and cardiovascular toxicity of CsA was associated with
      arterial dysfunction and morphological changes in small arteries and arterioles
      in SHR on a high-sodium diet. The findings did not support the role of oxidative
      stress or a defect in the L-arginine-NO pathway.

PMID- 11321511
TI  - Repetitive apneas reduce nonlinear dynamical complexity of the human
      cardiovascular control system.
AB  - We tested the hypothesis that intermittent apneas performed by awake subjects
      simulate obstructive sleep apnea (OSA) and change dynamic complexity of the
      cardiovascular control system by repetitive short time stimulation of arterial
      chemoreceptors. Correlation dimension (CD) and reccurent plot quantification
      calculated as ratio % determinism versus % recurrence (RDR) were used.as indices
      of chaotic dynamics. Thirty three normotensive subjects of mean age 21,58 +/- 4,1
      performed 10 voluntary apneas 1 min. each separated by 1 min free breathing
      period. Systolic (SYS), diastolic (DIAS) arterial blood pressure was continuously
      recorded by finger volume clamp. Stroke volume (SV) was estimated by pulse
      pressure analysis. Cardiac output (CO) and total peripheral resistance (TPR) were
      calculated by Portapress system. Cardiac inter-beat interval (IBI) was measured
      from R-R intervals of ECG. Standard deviation (SD), an index of linear
      variability, was calculated in 1 min epoch. Dynamics of cardiovascular variables
      was computed in each subject during 20 min. rest (C), 20 min. of 10 apneas, 1 min
      each, separated by 1 min free breathing (A), and in 20 min. recovery free
      breathing (R). In A period CD of all circulatory variables was significantly
      reduced and RDR augmented. In 23 out of 33 subjects decreased nonlinear dynamics
      of TPR was carried over from A to R. In contrast, SD increased significantly in
      A. In conclusion, intermittent brief chemoreflex stimulations by repetitive
      apneas increase blood pressure and TPR and decrease chaotic behaviour and
      complexity of the cardiovascular autonomic control system, presumably by
      inhibition of some regulatory loops such as baroreflex, less vital for survival
      at oxygen deprivation. Reduced complexity could be implicated in the mechanism of
      arterial hypertension linked with OSA.

PMID- 11321512
TI  - Relation between expression of TNF alpha, iNOS, VEGF mRNA and development of
      heart failure after experimental myocardial infarction in rats.
AB  - An injury to the heart due to myocardial infarction (MI) may progress to heart
      failure. Among factors, whose interactions promote remodeling of ischemic
      myocardium, the increased expression of tumor necrosis factor alpha (TNFalpha),
      inducible nitric oxide synthase (iNOS) and Vascular Endothelial Growth Factor
      (VEGF) was found. However, little is known about the temporal and spatial
      relation between expression of iNOS, cytokine TNFalpha, and growth factor VEGF
      during pathological process of development of heart failure after the myocardial
      infarction. Male Sprague-Dawley rats were used for experimental myocardial
      infarction. The procedure was performed by anterolateral thoracotomy and snearing
      LAD with the metal clip. The hemodynamic measurements were done with the
      Langendorff preparation converted into a working heart system. The hemodynamic
      parameters were recorded at day 6, 11, 28, 40 and the myocardium for gene
      expression was collected at day 1, 4, 11, 28, 40. Control group was sham operated
      rats. The VEGF, TNFalpha, iNOS, and GAPDH genes were detected by RT-PCR assay
      from samples taken at border zone of myocardial infarction. Expression of isoform
      VEGF120 was found at day 1 and 4 after MI, whereas isoforms VEGF164 and VEGF188
      along with expression of TNFalpha and iNOS was found at day 1, 4, 11, 28, 40. No
      expression of examined genes was detected in the myocardium of control rats. The
      expression of studied factors was parallel with development of heart failure
      after myocardial infarction assessed by hemodynamic measurements. These findings
      confirm the postulated involvement of TNFalpha, iNOS and growth factor VEGF in
      the remodeling of the myocardium and development of heart failure after
      experimental myocardial infarction.

PMID- 11321513
TI  - Leptin, gastrointestinal and stress hormones in response to exercise in fasted or
      fed subjects and before or after blood donation.
AB  - Leptin, an ob gene product of adipocytes, plays a key role in the control of food
      intake and energy expenditure but little is known about leptin response to
      strenuous exercise in fasted and fed subjects or before and after blood donation.
      This study was designed to determine the immediate effects of strenuous exercise
      in healthy volunteers under fasting or fed conditions and before and one day
      after blood donation (450 ml) on plasma levels of leptin and gut hormones
      [gastrin, cholecystokinin (CCK), pancreatic polypeptide (PP) and insulin], as
      well as on "stress" hormones (cortisol, catecholamines and growth hormone. Two
      groups (A and B) of healthy non-smoking male volunteers were studied. All
      subjects performed incremental exercise tests until exhaustion (up to maximal
      oxygen uptake--VO2max), followed by 2 h of rest session. Group A perfomed the
      tests on a treadmill, while group B on a cycloergometer. In group A, one exercise
      was performed under fasting conditions and the second following ingestion of a
      standard liquid meal. In group B, one exercise test was performed as a control
      test and the second 24 h after blood donation (450 ml). Blood samples were
      withdrawn 5 min before the start of the test, at the VO2max, and 2 h after
      finishing the exercise. No significant change in plasma teptin were observed both
      immediately and 2 h after the exercise in fasted subjects, but after the meal the
      plasma leptin at VO2max and 2 h after the test was significantly higher, while
      after blood donation was significantly reduced. The postprandial rise in plasma
      leptin was accompanied by a marked increment in gut hormones; gastrin, CCK and PP
      and stress hormones such as norepinephrine, cortisol and GH. These hormonal
      changes could contribute to the postprandial rise in plasma leptin
      concentrations, while the fall of leptin after blood donation could be attributed
      to the inadequate response of stress hormones and autonomic nervous system to
      exhausting exercise. We conclude that strenuous physical exercise; 1) fails to
      affect plasma leptin level but when performed after meal but not after blood
      withdrawal it results in an increase and fall in plasma leptin, and 2) the
      release of gut hormones (gastrin, CCK and PP) and stress hormones
      (norepinephrine, cortisol, GH) increase immediately after exercise independently
      of feeding or blood donation and 3) following blood donation the strenuous
      exercise resulted in a marked reduction in the plasma leptin, cortisol and GH
      concentrations, possibly due to the impairment in the autonomic nervous control
      of these hormones.

PMID- 11321514
TI  - Diverging respiratory effects of serotonin and nicotine in vagotomised cats prior
      to and after section of carotid sinus nerves.
AB  - Respiratory effects of intravenous serotonin and nicotine were investigated prior
      to and after bilateral neurotomy of the carotid sinus nerves (CSNs) in eight
      pentobarbitone/chloralose-anaesthetised, bilaterally vagotomised and superior
      laryngeal nerves-sectioned cats. Injection of 188 nmol kg(-1) serotonin (hydrogen
      oxalate salt, 50 microg x kg(-1)) prior to and after CSNs section induced an
      expiratory apnoea of, respectively, 7.9 +/- 1.25 s and 8.3 +/- 1.6 s duration
      (mean +/- S.E.M.) in, respectively, five and three of those cats. In all cats,
      the serotonin challenge produced a period of accelerated breathing (P < 0.05)
      both prior to and after section of CSNs. Injection of a 433 nmol nicotine bolus
      (hydrogen tartrate salt, 200 microg) increased tidal volume by 25 +/- 8% in cats
      with intact CSNs (P < 0.01), but decreased it by 13 + 10% (P < 0.05) after CSNs
      section. Nicotine, but not serotonin, transiently increased mean arterial blood
      pressure in our cats, which rise was delayed by CSNs cut. Results of this study
      indicate that the respiratory response to serotonin occurs beyond carotid body
      chemoreceptors in vagotomised cats, and suggest that the volume response to
      intravenous nicotine depends qualitatively on carotid body chemoreceptor input in
      this experimental model.

PMID- 11321515
TI  - Nonsteroidal anti-inflammatory drugs impair oral mucosal repair by eliciting
      disturbances in endothelin-converting enzyme-1 and constitutive nitric oxide
      synthase.
AB  - Although the use of nonsteroidal anti-inflammatory drugs (NSAIDs) is known to
      cause the impairment in mucosal defenses that are well recognized and clinically
      emphasized with respect to the gastrointestinal tract, less apparent is the
      extent of their interference with the repair of soft oral tissue. As the
      disturbances in nitric oxide generation and the release of endothelin-1 (ET-1)
      are the early signs of injury by NSAIDs, we investigated oral mucosal ulcer
      healing in the presence of NSAID administration by analyzing the expression of
      endothelin-converting enzyme-1(ECE-1), responsible for ET-1 generation, and the
      mucosal activity of inducible (NOS-2) and constitutive (cNOS) nitric oxide
      synthase responsible for nitric oxide production. Groups of rats with acetic
      induced buccal mucosal ulcers were subjected twice daily for up to 10 days to
      intragastric administration of either indomethacin (5 mg/kg), aspirin (20 mg/kg),
      or the vehicle and their mucosal tissue subjected to macroacopic assessment of
      ulcer healing rate and biochemical measurements. While in the control group the
      ulcer healed by the tenth day, only a 57.2% reduction in the ulcer crater area
      was attained in the animals subjected to indomethacin and a 54.8% reduction in
      ulcer occurred in the presence of aspirin administration. Futhermore, by the
      tenth day, the delay in healing in the presence of indomethacin was manifested by
      a 4.9-fold higher rate of apoptosis, a 2.7-fold higher expression of ECE-1
      activity, a 3.9-fold higher expression of NOS-2 activity and a 2.2-fold decline
      in cNOS activity, while the interference in ulcer healing by aspirin was
      characterized by a 5.6-fold higher rate of apoptosis, a 2.8-fold expressiom of
      ECE-1 activity, a 3.7-fold higher expression of NOS-2 activity and a 2.3-fold
      lower expression of cNOS activity. Our findings demonstrate that NSAIDs not only
      pose a well-known risk of gastrointestinal injury, but also interfere with soft
      oral tissue repair. The impairment in buccal mucosal ulcer healing by NSAID
      ingestion is manifested in up-regulation in the expression of ECE-1 responsible
      for ET-1 generation, suppression in cNOS, and amplification of apoptotic events
      that delay the healing process.

PMID- 11321516
TI  - Stimulation by nitric oxide of gastric acid secretion in bullfrog fundic mucosa
      in vitro.
AB  - We examined the effect of NO on acid secretion in vitro using isolated
      preparations of Bullfrog stomach. The bullfrog fundic mucosa was bathed in
      unbuffered Ringer solution gassed with 100% O2 on the mucosal side and HCO3-
      Ringer's solution gassed with 95% O2/5% CO2 on the serosal side, and the acid
      secretion was measured at pH 5.0 using the pH-stat method and by adding 5 mM
      NaOH. Serosal addition of a NO donor NOR-3 (10(-5) approximately 10(-3) M: (+/-)
      (E)-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexnamine) caused an increase of acid
      secretion in a dose-dependent manner, the effect lasting about 1 hr and reaching
      a maximal level of 2-fold the basal values. The acid stimulatory effect of NOR-3
      was mimicked by another NO donor SNAP (10(-3) mol/L: S-nitroso-O-N-acetyl
      penicillamine) and markedly and markedly inhibited by prior administration of
      cimetidine (10(-5) mol/L) as well as compound 48/80 (the mast cell degranulator).
      Likewise, the increased acid response to NOR-3 was significantly mitigatd by
      pretreatment with carboxy-PTIO (a NO scavenger) or superoxide dismutase (SOD),
      but not by indomethacin or methylene blue (a guanylyl cyclase inhibitor).
      Neoither L-NAME, L-arginine nor dibutyryl guanosine-3',5'-cyclic monophosphate
      (dbcGMP) has any effect on the basal acid secretion. Serosal addition of NOR-3
      caused a significant increase in the luminal release of histamine, and this
      response was inhibited by pretreatment with either compound 48/80, carboxy-PTIO
      or SOD. These results suggest that the NO donor increases gastric acid secretion
      in the isolated frog stomach in vitro, and this action is mediated by endogenous
      histamine released from mast cells, the process being cGMP-independent but
      requiring the presence of superoxide radicals. In addition, it was speculated
      that the histamine releasing action of NO may be due to peroxynitrite produced by
      NO and superoxide radicals.

PMID- 11321517
TI  - Superporous agarose monoliths as mini-reactors in flow injection systems. On-line
      monitoring of metabolites and intracellular enzymes in microbial cultivation
      processes.
AB  - A new type of agarose material, superporous agarose, was used as a support
      material in an analytical system designed for monitoring of bioprocesses with
      respect to metabolites and intracellular enzymes. The superporous agarose was
      used in the form of miniaturised gel plug columns (15 x 5.0 mM I.D. monolithic
      gel bed). The gel plugs were designed to have one set of very large pores (about
      50 microm in diameter) through which cells, cell debris and other particulate
      contaminants from the bioreactor could easily pass. The material also had normal
      diffusion pores (300 A) characteristic of all agarose materials, providing ample
      surface for covalent attachment of antibodies and enzymes used in the analytical
      sequence. The superporous agarose gel plug columns were characterised with
      respect to flow properties and handling of heavy cell loads as well as dispersion
      of injected samples (a Bodenstein number of about 40 was observed with acetone
      tracer at a flow rate of 1 ml min(-1)). To evaluate the practical performance of
      the superporous gel plug columns, two applications were studied: (1) on-line
      determination of glucose in cultivation broth (gel plug with immobilized glucose
      oxidase) and (2) immunochemical quantification of intracellular beta
      galactosidase in E. coli (gel plug with lysozyme to achieve cell lysis and gel
      plug with antibodies against beta-galactosidase).

PMID- 11321518
TI  - Effect of salts and surfactants on the partitioning of Fusarium solani pisi
      cutinase in aqueous two-phase systems of thermoseparating ethylene
      oxide/propylene oxide random copolymer and hydroxypropyl starch.
AB  - An aqueous two-phase system composed by a thermoseparating random copolymer of
      ethylene oxide/propylene oxide 50/50 (%w/w), Breox, and hydroxypropyl starch
      Reppal PES 100 was evaluated for the partitioning of Fusarium solani pisi
      recombinant cutinase. The effect of several additives on the partitioning of pure
      cutinase was evaluated. Micelles of sodium dodecanoate provided a ten-fold
      increase of the partitioning coefficient (K=9) and recovery yields of 60-75%. The
      phase diagrams of the systems composed of Breox, Reppal and sodium dodecanoate
      were determined and it was found that in systems with high surfactant
      concentrations, the binodal was moved to lower polymer concentrations, enabling a
      two-phase system with 6% (w/w) of each polymer.

PMID- 11321519
TI  - New method for the selective capture of antibodies under physiological
      conditions.
AB  - Hydrophobic charge induction chromatography is a recently developed method for
      protein separation based on the use of dual-mode ligands. They are designed in
      such a way so as to combine a molecular interaction supported by a mild
      hydrophobic association effect in the absence of salts. When environmental pH is
      changed, the ligand becomes ionically charged resulting into the desorption of
      the protein. This method is applied to the separation of antibodies from ascite
      fluids and culture supernatants from hybridomas cultured in the presence of fetal
      bovine serum or in protein free environment. Typically adsorption from cell
      culture supernatants is accomplished without any pH or ionic strength adjustment;
      the column is then washed with a typical buffer to eliminate protein impurities.
      Antibodies are then desorbed using acetate buffer, pH 4. Antibody binding
      capacity is in the range of 30 mg per ml of resin at 10% breakthrough. Antibody
      purity varies according to the initial feed stock and can reach values higher
      than 90% in a single pass. One example of antibody purification process involving
      hydrophobic charge induction chromatography as a capture step followed by a
      polishing phase with DEAE Ceramic HyperD is described. Longevity and ligand
      leakage are compatible with large-scale applications.

PMID- 11321520
TI  - Recovery of mouse endostatin produced by Pichia pastoris using expanded bed
      adsorption.
AB  - Endostatin, a 20 KDa fragment of collagen XVIII, was shown to have an inhibitory
      effect on angiogenesis and can potentially be used as a tumor growth suppressor.
      To obtain the amount needed for testing, the protein was successfully cloned and
      expressed in Pichia pastoris. At the end of the fermentation process, the
      concentration of the endostatin in the culture was 50 mg per liter, accompanied
      by 400 gr per liter (wet weight) of biomass. Before the protein can be captured
      and purified on a packed bed of heparin-Sepharose, the biomass must be removed.
      Because of the high biomass concentration, conventional biomass removal
      techniques like centrifugation or filtration are inefficient and cumbersome.
      Therefore, the expanded-bed adsorption technique was chosen as an alternative
      approach. An efficient procedure for the initial recovery and purification of the
      endostatin was developed. The process utilized a cation- exchanger resin instead
      of a heparin-based affinity resin, because its dynamic capacity was higher, even
      though it was affected by the high linear flow on the expanded bed. After
      adjusting the conductivity, pH and biomass concentration, the complete broth was
      pumped directly on the expanded-bed matrix (Streamline SP XL). Though the yields
      of protein are similar, the expanded-bed approach is superior to the packed-bed
      method for several reasons. The expanded-bed process was shorter (only 8 hours
      compared to 16 hours for the packed bed), it is cheaper, and the product has
      higher specific activity (29% compared with 18%). Endostatin produced by the
      expanded-bed adsorption method showed the expected bioactivity and is currently
      being tested for its potential as a tumor suppressor.

PMID- 11321521
TI  - Scale-up of recombinant cutinase recovery by whole broth extraction with PEG
      phosphate aqueous two-phase.
AB  - A whole broth extraction using an aqueous two-phase system (ATPS) composed by 5%
      (w/w) PEG 3350 and 15% (w/w) phosphate was used for the scale-up extraction and
      isolation of a recombinant Fusarium solani pisi cutinase, an extracellular mutant
      enzyme expressed in Saccharomyces cerevisiae, containing a fusion peptide (WP)4.
      The experiments were carried out at three different scales (10 ml, 1 l and 30 l).
      Mixing time and stirrer speed were evaluated at lab scale (1 l) with two
      different system compositions. Stirrer speed between 400 and 800 rpm and mixing
      time between 2 and 5 min led to the highest recoveries of cutinase. In all cases,
      inclusive of pilot scale (30 l), the equilibrium was reached after a few minutes.
      The performance of ATPS was reproducible within the scale range of 0.010-30 l and
      provided a standard deviation of the yield lower than 8%, leading to (i) a
      partition coefficient over 50, (ii) a yield over 95% and (iii) a concentration
      factor over 5. The fusion of the peptide (WP)4 to the cutinase protein enabled a
      400 increase of the partition coefficient relative to the wild-type strain.

PMID- 11321522
TI  - Purification of a 'double-headed' inhibitor of alpha-amylase/proteinase K from
      wheat germ by expanded bed chromatography.
AB  - The double-headed inhibitor of alpha-amylase and Proteinase K was purified from
      wheat germ using Cu(II)-Streamline-chelating resin. The endogenous alpha-amylase
      could be inactivated by heating. Followed by this step, both packed bed and
      expanded bed gave similar activity yield of around 83% and fold purification
      around 23. In the case of expanded bed, it was not necessary to separate
      precipitated protein before the chromatography. The purified preparation gave a
      single band on SDS-PAGE and the estimated molecular weight of 21 kDa was in
      agreement with the reported value for the inhibitor designated as PKI-3 in the
      literature.

PMID- 11321523
TI  - Recovery of endo-polygalacturonase using polyethylene glycol-salt aqueous two
      phase extraction with polymer recycling.
AB  - The partitioning behaviour of endo-polygalacturonase (endo-PG) and total protein
      from a clarified Kluyveromyces marxianus fermentation broth in polyethylene
      glycol (PEG)-ammonium sulfate and PEG-potassium phosphate (pH=7) aqueous two
      phase systems was experimentally investigated. Both the enzyme and total protein
      partitioned in the bottom phase for these two kinds of systems. The enzyme
      partitioning coefficient can be lower than 0.01 in PEG8000-(NH4)2SO4 ATPS with a
      large phase volume ratio and a moderate tie-line length, which implies the
      possibility of concentration operation using aqueous two phase partitioning. An
      ion-exchange separation of high purification efficiency was applied to analyze
      the clarified and dialyzed fermentation broth. A total purification factor of
      only 2.3 was obtained, which indicated the high enzyme protein content in the
      total protein of the fermentation broth. Consequently, the main purpose for
      separating endo-PG is concentration rather than purification. A separation scheme
      using an aqueous two-phase extraction process with polymer recycling and a
      dialysis was proposed to recover endo-PG from the fermentation supernatant of K.
      marxianus for commercial purpose. A high enzyme recovery up to 95% and a
      concentration factor of 5 to 8 with a purification factor of about 1.25 were
      obtained using the single aqueous two-phase extraction process. More than 95%
      polymer recycled will not affect the enzyme recovery and purification factor.
      Dialysis was used mainly to remove salts in the bottom phase. The dialysis step
      has no enzyme loss and can further remove small bulk proteins. The total
      purification factor for the scheme is about 1.7.

PMID- 11321524
TI  - P-glycoprotein, glutathione and glutathione S-transferase increase in a colon
      carcinoma cell line by colchicine.
AB  - The acquisition of resistance to anticancer agents used in chemotherapy is the
      main cause of treatment failure in malignant disorders, provoking tumours to
      become resistant during treatment, although they initially respond to it. The
      main multidrug resistance (MDR) mechanism in tumour cells is the expression of P
      gly-coprotein (P-gly), that acts as an ATP-dependent active efflux pump of
      chemotherapeutic agents. Furthermore, an increased detoxification of compounds
      mediated by high levels of glutathione (GSH) and glutathione S-transferase (GST),
      has been found in resistant cells. We developed a study aiming to evaluate the
      evolution of the main drug resistance markers in tumour cells: P-gly, GSH and
      GST, during the acquisition of resistance to colchicine, for the purpose of
      studying the adaptation process and its contribution to the MDR phenomenon. A
      human colon adenocarcinoma cell line was exposed to colchicine during 82 days,
      being P-gly, GSH levels and GST activity evaluated by flow cytometry,
      spectrofluorimetry and spectrophotometry, during exposure time. P-gly and GSH
      levels increased gradually during the exposure to colchicine, reaching 2.35 and
      3.21 fold each. On day 82, GST activity increased 1.84 fold at the end of the
      exposure period. Moreover, an increment in drug cross-resistance was obtained
      that ranges from 2.62 to 5.22 fold for colchicine, vinblastine, vincristine and
      mitomycin C. The increments obtained in P-gly, GSH and GST could probably
      contribute to the MDR phenomenon in this human colon adenocarcinoma cell line.

PMID- 11321525
TI  - The hippocampus and flexible spatial knowledge in rats.
AB  - Lesions to the hippocampal system in rats result in a profound impairment of
      place or locale spatial learning although other learning strategies remain
      unaltered. The main objective of the present study was to investigate whether the
      spatial knowledge preserved in the hippocampal animals can be expressed flexibly
      under conditions different from those of the acquisition period. Rats with
      neurotoxic lesions to the dorsal hippocampus and sham-operated subjects were
      trained to reach the goal arm in a four-arm plus-shaped maze using a constant
      starting arm. During the training a transparent plexiglas barrier divided the
      maze in two equal halves in such a way that the animals could only travel from
      the starting arm to the goal arm, not having access to the remaining 50% of the
      maze. After seven days of training, a transfer test was used in which the
      starting arms were the two arms from which the animals had not started during the
      training phase. Results indicated that the lesioned rats made significantly more
      errors than the control subjects. But the most interesting results revealed that
      the kind of error made by the lesioned animals was congruent with the turn that
      they had to make during the acquisition phase in order to access the goal arm
      (reinforced). These results suggest that when the hippocampus is damaged a
      preserved highly inflexible egocentric strategy is employed to solve the spatial
      problem.

PMID- 11321526
TI  - Effects of hypoxic preconditioning on the hypoxic-reoxygenated atria from fed and
      fasted rats.
AB  - Hypoxic preconditioning (PC) was studied using rat atria set up isometrically in
      10 mM dextrose medium and paced at 1 Hz, applying three different protocols
      wherein fed and 24-h fasted rats were used in protocols 1 and 2 and only the fed
      in protocol 3. In protocol 1, PC was achieved applying a 5 min hypoxia followed
      by 10 min of reoxygenation before the onset of a 60 min hypoxia and 60 min
      reoxygenation. In protocol 2 the 5 min and a posterior 45 min hypoxia were
      applied in the absence of dextrose whereas in the 10 min and 60 min reoxygenation
      periods dextrose was present. In protocol 3, two cycles of 5 min dextrose-free
      hypoxic periods were applied before the sustained hypoxia (dextrose-free) and
      reoxygenation periods (10 min and final 45 min, both in the presence of
      dextrose). In the control groups of all protocols, the equilibration periods were
      prolonged to compensate the duration of PC. In the control groups of protocols 1
      and 2, the sustained hypoxia evoked greater disturbances of contractility and a
      smaller post-hypoxic recovery in the fasted than in the fed rat atria. In
      protocol 1, PC markedly reduced the rise in resting tension and improved the post
      hypoxic recovery in the fasted rat atria whereas in the fed rat atria protective
      effects were small and brief. In protocol 2, PC evoked a small reduction of
      contracture only in the atria from fasted rats and in protocol 3, PC exacerbated
      the hypoxic disturbances. These data suggest that PC effects depend both on the
      severity of the PC stress and the sustained hypoxia; and that PC does not require
      coronary flow.

PMID- 11321527
TI  - The effects of different anaesthetic treatments on the adreno-cortical functions
      and glucose levels in NZW rabbits.
AB  - The effects of five anaesthetics on the corticosterone, cortisol and glucose
      concentrations were investigated in the NZW rabbit. Sixty animals were assigned
      to 6 treatment groups (n= 10 per group): control ( iv saline solution injection),
      ketamine (10 mg/kg iv) with either xylazine (3 mg/kg iv) or diazepam (2 mg/kg
      iv), pentobarbitone (30 mg/kg iv), thiopentone (20 mg/kg iv) and
      fentanyl/droperidol (1 mg/kg sc). Plasma glucocorticoids were measured by
      competitive enzymeimmunoassay EIA and glucose by an autoanalyzer, previously
      validated for this species in both cases. Blood samples were obtained at 6 time
      points: before injection, at 10, 30, 60, 120 min and 24 h after injection of the
      anaesthetics/saline. A significant decrease of plasma glucocorticoids at 10-60
      min was observed in the pentobarbitone and fentanyl/ droperidol groups, whereas
      the administration of ketamine/diazepam or thiopentone stimulated plasma
      glucocorticoid release, principally in the recovery period. However, in the
      ketamine/xylazine group no changes were observed in the glucocorticoid levels,
      except for a significative increase of cortisol at 60-120 min. Glucose levels
      significantly increased after ketamine/diazepam administration and principally,
      after ketamine/xylazine treatment. The present data suggest that
      ketamine/xylazine has little effect on glucocorticoid levels and provides an
      adequate level of surgical anaesthesia, hence it would be the anaesthetic of
      choice, although the hyperglycaemic effect after injection has to be considered
      for any experimental procedures in rabbits.

PMID- 11321528
TI  - Effects of medium-chain fatty acids on body composition and protein metabolism in
      overweight rats.
AB  - The lack of efficiency of classical treatments for obesity has led to propose
      alternative strategies. In order to obtain information about the effects of
      dietary fatty acid composition on body fat and protein metabolism, overweight
      female rats were fed on isoenergetic diets, using either medium-chain (MCT) or
      long-chain (LCT) triglycerides as a lipid source. After 23 days, the MCT group
      had mildly decreased body weight but greatly reduced adipose tissue depots. All
      fat depots were significantly diminished. MCT-fed rats showed a decrease in some
      hormones involved in energy balance, such as leptin and triiodothyronine. Feeding
      MCT resulted in improvements in nitrogen balance. Muscle protein content was
      similar in both treatments despite an increase in protein degradation in the MCT
      group. The present data clearly show that a diet with MCT as lipid fuel depresses
      weight gain and fat stores, relative to a standard LCT diet.

PMID- 11321529
TI  - Effects of sea urchin-based diets on serum lipid composition and on intestinal
      enzymes in rats.
AB  - The dietary effects of two high protein diets from two species of sea urchin
      (Paracentrotus lividus and Echinus esculentus) as compared to a reference protein
      such as casein on serum lipid levels and on intestinal disaccharidases and
      alkaline phosphatase were studied. After 23 days, the containing the two sea
      urchins as diets compared to casein decreased the cholesterol level and
      significantly increased the HDL-cholesterol in serum. The consumption of Echinus
      esculentus meal produced a significant decrease in lactase activity. The
      intestinal alkaline phosphatase activity increased not significantly in animals
      fed on the sea urchin meal.

PMID- 11321530
TI  - Platelet GP Ib/IX/V complex: physiological role.
AB  - Platelets play an essential role in primary hemostasis and in thrombotic events,
      particularly in arterial vessels, as rheological conditions originate closer
      interactions between platelets and endothelium than lower shear rates. In
      response to vascular injury, platelets adhere to the subendothelial matrix by
      membrane receptors potentiating the generation of thrombin, become activated, and
      a series of biochemical processes induce platelet aggregation and liberation of
      intracellular metabolic products to the extracelular medium. Among platelet
      receptors, glycoprotein (GP) Ib/IX/V complex is peculiar, as it binds adhesive
      proteins, mainly von Willebrand factor (vWF), and thrombin, the main platelet
      agonist. Platelet adhesion and subsequent aggregation under conditions of high
      shear flow, essentially relies upon this receptor's capacity of binding to the
      subendothelial matrix, initiating signal transduction. Two proteins associated to
      GP Ib/IX/V, actin-binding protein (ABP) 280 and 14-3-3zeta, are potential
      mediators of signal transduction by the complex, but their specific contribution
      in this process is not yet fully understood. Additionally, two proteins
      implicated in signal transduction by immune stimuli, FcgammaRIIA and FcR gamma
      chain, associate with GPIb/IX/V complex, and increasing data indicate a potential
      role in GPIbalpha mediated signal transduction.

PMID- 11321531
TI  - Oleoyl-estrone treatment reduces the volume of white adipose tissue cells in the
      rat.

PMID- 11321533
TI  - Differential expression of antenna and core genes in Prochlorococcus PCC 9511
      (Oxyphotobacteria) grown under a modulated light-dark cycle.
AB  - The continuous changes in incident solar light occurring during the day oblige
      oxyphototrophs, such as the marine prokaryote Prochlorococcus, to modulate the
      synthesis and degradation rates of their photosynthetic components finely. How
      this natural phenomenon influences the diel expression of photosynthetic genes
      has never been studied in this ecologically important oxyphotobacterium. Here,
      the high light-adapted strain Prochlorococcus sp. PCC 9511 was grown in large
      volume continuous culture under a modulated 12 h-12 h light-dark cycle mimicking
      the conditions found in the upper layer of equatorial oceans. The pcbA gene
      encoding the major light-harvesting complex showed strong diel variations in
      transcript levels with two maxima, one before the onset of illumination and the
      other near the end of the photoperiod. In contrast, the mRNA level of psbA
      (encoding the reaction centre II subunit D1), the monocistronic transcript of
      psbD (encoding D2) and the dicistronic transcript of psbDC were all tightly
      correlated with light irradiance, with a minimum at night and a maximum at noon.
      The occurrence of a second peak during the dark period for the monocistronic
      transcript of psbC (encoding one of the PS II core Chl a antenna proteins)
      suggested the involvement of post-transcriptional regulation. Differential
      expression of the external antenna and core genes may constitute a mechanism of
      regulation of the antenna size to cope with the excess photon fluxes that
      Prochlorococcus cells experience in the upper layer of oceans around midday. The
      5' ends of all transcripts were mapped, and a conserved motif, 5'-TTGATGA-3', was
      identified within the putative psbA and pcbA promoters.

PMID- 11321532
TI  - Phylogenetic characterization of epibiotic bacteria in the accessory nidamental
      gland and egg capsules of the squid Loligo pealei (Cephalopoda:Loliginidae).
AB  - Sexually mature female squid Loligo pealei harbour dense bacterial communities in
      their accessory nidamental glands (ANGs) and in their egg capsules (ECs). This
      study describes a molecular approach using the 16S rRNA gene (rDNA) to identify
      bacterial populations within the ANG and the ECs of the North Atlantic squid
      species L. pealei. Fluorescent in situ hybridization (FISH) and 16S rDNA analysis
      showed that predominantly alpha- and, to a lesser extent, gamma-proteobacteria
      were the predominant components of the ANG and EC bacterial communities.
      Sequencing results showed the presence of alpha-proteobacterial populations
      affiliated with the Roseobacter group and additional deep-branching alpha
      proteobacterial lineages. In contrast, isolates from the ANG and ECs contained
      only a few alpha-proteobacteria of the Roseobacter group compared with several
      gamma-proteobacterial isolates, mostly Shewanella and Pseudoalteromonas species.
      Most of the ANG-associated bacterial populations were also found within the ECs
      of L. pealei. The molecular approach allowed the visualization of alpha
      proteobacteria as major constituents of a bacterial symbiosis within the
      reproductive system of the Loliginidae.

PMID- 11321534
TI  - The structure of a local population of phytopathogenic Pseudomonas brassicacearum
      from agricultural soil indicates development under purifying selection pressure.
AB  - Among the isolates of a bacterial community from a soil sample taken from an
      agricultural plot in northern Germany, a population consisting of 119 strains was
      obtained that was identified by 16S rDNA sequencing and genomic fingerprinting as
      belonging to the recently described species Pseudomonas brassicacearum. Analysis
      of the population structure by allozyme electrophoresis (11 loci) and random
      amplified polymorphic DNA-polymerase chain reaction (RAPD-PCR; four primers)
      showed higher resolution with the latter method. Both methods indicated the
      presence of three lineages, one of which dominated strongly. Stochastic tests
      derived from the neutral theory of evolution (including Slatkin's exact test,
      Watterson's homozygosity test and the Tajima test) indicated that the population
      had developed under strong purifying selection pressure. The presence of strains
      clearly divergent from the majority of the population can be explained by in situ
      evolution or by influx of strains as a result of migration or both.
      Phytopathogenicity of a P. brassicacearum strain determined with tomato plants
      reached the level obtained with the type strain of the known pathogen Pseudomonas
      corrugata. The results show that a selective sweep was identified in a local
      population. Previously, a local selective sweep had not been seen in several
      populations of different bacterial species from a variety of environmental
      habitats.

PMID- 11321535
TI  - Bacterial populations occuring in a trichloroethylene-contaminated aquifer during
      methane injection.
AB  - Soil core samples were obtained from a trichloroethylene (TCE)-contaminated
      aquifer before and after the start of methane biostimulation. DNA was extracted
      directly from the soil samples, and denaturing gradient gel electrophoresis
      (DGGE) was used to analyse bacterial 16S ribosomal DNA fragments that were PCR
      amplified from these DNA samples. This analysis consistently detected two
      phylotypes in the methane-injected samples. These phylotypes were closely related
      to Methylobacter and Methylomonas, both belonging to type I methanotrophs. A
      competitive DGGE analysis using Methylosinus trichosporium OB3b cells as an
      internal quantitative standard showed that these populations accounted for 10(8)
      10(9) cells g(-1) soil. These results showed that type I methanotrophs formed a
      significant proportion of the bacterial community during methane biostimulation.
      The implications of this finding for TCE bioremediation were discussed.

PMID- 11321536
TI  - Molecular analyses of methyl-coenzyme M reductase alpha-subunit (mcrA) genes in
      rice field soil and enrichment cultures reveal the methanogenic phenotype of a
      novel archaeal lineage.
AB  - The diversity of methanogen-specific methyl-coenzyme M reductase alpha-subunit
      (mcrA/mrtA) genes in Italian rice field soil was analysed using a combination of
      molecular techniques and enrichment cultures. From 75 mcrA/mrtA clones retrieved
      from rice field soil, 52 were related to members of the Methanosarcinaceae,
      Methanosaetaceae and Methanobacteriaceae. However, 19 and four clones formed two
      novel clusters of deeply branching mcrA sequences, respectively, which could not
      be affiliated to known methanogens. A new methanogen-specific fingerprinting
      assay based on terminal restriction fragment length polymorphism (T-RFLP)
      analysis of fluorescently labelled polymerase chain reaction (PCR) products
      allowed us to distinguish all environmental mcrA/mrtA sequences via group
      specific Sau96I restriction sites. Even genes for the isoenzyme methyl-coenzyme M
      reductase two (mrtA) of Methanobacteriaceae present in rice field soil were
      represented by a unique 470 bp terminal restriction fragment (T-RF). Both cloning
      and T-RFLP analysis indicated a significant representation of novel environmental
      mcrA sequences in rice field soil (238 bp T-RF). To identify these mcrA
      sequences, methanogenic enrichment cultures with rice field soil as inoculum were
      established with H2/CO2 as substrates at a temperature of 50 degrees C, and these
      were monitored using molecular tools. In subsequent transfers of these enrichment
      cultures, cloning and T-RFLP analysis detected predominantly SSU rRNA genes of
      rice cluster I (RC-I), an uncultivated euryarchaeotal lineage discovered
      previously in anoxic rice field soil. In parallel, both mcrA cloning and T-RFLP
      analyses of the enrichment culture identified the more frequent cluster of novel
      environmental mcrA sequences as belonging to members of RC-I. Thus, we could
      demonstrate the genotype and phenotype of RC-I Archaea by the presence of a
      catabolic gene in a methanogenic enrichment culture before the isolation of pure
      cultures.

PMID- 11321537
TI  - Microbiological, molecular biological and stable isotopic evidence for nitrogen
      fixation in the open waters of Lake Michigan.
AB  - We have used a combination of microbiological, molecular biological and stable
      isotope methods to relate specific microbial populations to elemental cycling at
      an offshore site in Lake Michigan. Several lines of evidence suggest that
      atmospheric N2 may be a significant source of nitrogen to the lake. Particulate
      organic nitrogen (PON) at approximately equals 10-15m depth in July and October
      had a delta15N of 0.5-1.5%o. These values closely reflect the 15N composition of
      atmospheric N2, suggesting biological nitrogen fixation. Historical data show a
      developing late-summer N:P minimum at approximately equals 15 m; low abundance of
      inorganic nitrogen relative to phosphorus favours species able to acquire
      atmospheric nitrogen. Microscopic examination of October water samples revealed
      abundant heterocystous cyanobacteria, including Nodularia sp. Potentially
      nitrogen-fixing Anabaena spp. have been found in Lake Michigan before but, to our
      knowledge, this is the first report of Nodularia. Finally, we have amplified both
      cyanobacterial and non-cyanobacterial nifH sequences (encoding the nitrogenase
      iron protein) from lakewater samples, evidence for the presence of bacteria
      capable of nitrogen fixation. The surface waters of Lake Michigan are considered
      to be phosphate limited in the stratified season and, under these conditions,
      energetically expensive nitrogen fixation is expected to be uncompetitive with
      assimilation of combined nitrogen. Our results suggest that, from both
      microbiological and biogeochemical perspectives, this may be an
      oversimplification.

PMID- 11321539
TI  - Web alert. Antibiotics and antibiotic resistance in the environment.

PMID- 11321538
TI  - Isolate PM1 populations are dominant and novel methyl tert-butyl ether-degrading
      bacterial in compost biofilter enrichments.
AB  - The gasoline additive MTBE, methyl tert-butyl ether, is a widespread and
      persistent groundwater contaminant. MTBE undergoes rapid mineralization as the
      sole carbon and energy source of bacterial strain PM1, isolated from an
      enrichment culture of compost biofilter material. In this report, we describe the
      results of microbial community DNA profiling to assess the relative dominance of
      isolate PM1 and other bacterial strains cultured from the compost enrichment.
      Three polymerase chain reaction (PCR)-based profiling approaches were evaluated:
      denaturing gradient gel electrophoresis (DGGE) analysis of 230 bp 16S rDNA
      fragments; thermal gradient gel electrophoresis (TGGE) analysis of 575 bp 16S
      rDNA fragments; and non-denaturing polyacrylamide gel electrophoresis of 300
      1,500 bp fragments containing 16S/23S ribosomal intergenic transcribed spacer
      (ITS) regions. Whereas all three DNA profiling approaches indicated that PM1-like
      bands predominated in mixtures from MTBE-grown enrichments, ITS profiling
      provided the most abundant and specific sequence data to confirm strain PM1's
      presence in the enrichment. Moreover, ITS profiling did not produce non-specific
      PCR products that were observed with T/DGGE. A further advantage of ITS community
      profiling over other methods requiring restriction digestion (e.g. terminal
      restriction fragment length polymorphisms) was that it did not require an
      additional digestion step or the use of automated sequencing equipment. ITS
      bands, excised from similar locations in profiles of the enrichment and PM1 pure
      culture, were 99.9% identical across 750 16S rDNA positions and 100% identical
      across 691 spacer positions. BLAST comparisons of nearly full-length 16S rDNA
      sequences showed 96% similarity between isolate PM1 and representatives of at
      least four different genera in the Leptothrix subgroup of the beta-Proteobacteria
      (Aquabacterium, Leptothrix, Rubrivivax and Ideonella). Maximum likelihood and
      parsimony analyses of 1,249 nucleotide positions supported isolate PM1's position
      in a separate lineage within the Leptothrix subgroup.

PMID- 11321540
TI  - Nitrate-dependent iron(II) oxidation in paddy soil.
AB  - Iron(III) profiles of flooded paddy soil incubated in the greenhouse indicated
      oxidation of iron(II) in the upper 6 mm soil layer. Measurement of oxygen with a
      Clark-type microelectrode showed that oxygen was only responsible for the
      oxidation of iron(II) in the upper 3 mm. In the soil beneath, nitrate could be
      used as electron acceptor instead of oxygen for the oxidation of the iron(II).
      Nitrate was still available 3 mm below the soil surface, and denitrifying
      activity was indicated by higher concentrations of nitrite between 3 and 6 mm
      soil depth. Nitrate was generated by nitrification from ammonium. Ammonium
      concentrations increased beneath 6 mm soil depth, indicating ammonium release and
      diffusion from deeper soil layers. High concentrations of ammonium were also
      found at the surface, probably resulting from N2 fixation by cyanobacteria.
      Experimental adjustment of the nitrate concentration in the flooding water to 200
      microM stimulated nitrate-dependent iron(II) oxidation, which was indicated by
      significantly lower iron(II) concentrations in soil layers in which nitrate
      dependent iron(II) oxidation was proposed. Soil incubated in the dark showed high
      iron(III) concentrations only in the layer where oxygen was still available. In
      this soil, the nitrogen pool was depleted because of the lack of N2 fixation by
      cyanobacteria. In contrast, soil incubated in the dark with 500 microM nitrate in
      the flooding water showed significantly higher iron(II) and significantly lower
      iron(II) concentrations in the anoxic soil layers, indicating nitrate-dependent
      iron(II) oxidation. Anoxic incubations of soil with nitrate in the flooding water
      also showed high concentrations of iron(II) and low concentrations of iron(II) in
      the upper 3 mm. As oxygen was excluded in anoxic incubations, the high iron(III)
      concentrations are a sign of the activity of nitrate-dependent iron(II)
      oxidizers. The presence of these bacteria in non-amended soil was also indicated
      by the most probable number (MPN) counts of nitrate-dependent iron(II) oxidizers
      in the layer of 3-4 mm soil depth, which revealed 1.6 x 10(6) bacteria g(-1) dry
      weight.

PMID- 11321541
TI  - In situ identification of polyphosphate- and polyhydroxyalkanoate-accumulating
      traits for microbial populations in a biological phosphorus removal process.
AB  - Polyphosphate- and polyhydroxyalkanoate (PHA)-accumulating traits of predominant
      microorganisms in an efficient enhanced biological phosphorus removal (EBPR)
      process were investigated systematically using a suite of non-culture-dependent
      methods. Results of 16S rDNA clone library and fluorescence in situ hybridization
      (FISH) with rRNA-targeted, group-specific oligonucleotide probes indicated that
      the microbial community consisted mostly of the alpha- (9.5% of total cells),
      beta- (41.3%) and gamma- (6.8%) subclasses of the class Proteobacteria,
      Flexibacter-Cytophaga (4.5%) and the Gram-positive high G+C (HGC) group (17.9%).
      With individual phylogenetic groups or subgroups, members of Candidatus
      Accumulibacter phosphatis in the beta-2 subclass, a novel HGC group closely
      related to Tetrasphaera spp., and a novel gamma-proteobacterial group were the
      predominant populations. Furthermore, electron microscopy with energy-dispersive
      X-ray analysis was used to validate the staining specificity of 4,6-diamino-2
      phenylindole (DAPI) for intracellular polyphosphate and revealed the composition
      of polyphosphate granules accumulated in predominant bacteria as mostly P, Ca and
      Na. As a result, DAPI and PHA staining procedures could be combined with FISH to
      identify directly the polyphosphate- and PHA-accumulating traits of different
      phylogenetic groups. Members of Accumulibacter phosphatis and the novel gamma
      proteobacterial group were observed to accumulate both polyphosphate and PHA. In
      addition, one novel rod-shaped group, closely related to coccus-shaped
      Tetrasphaera, and one filamentous group resembling Candidatus Nostocoidia
      limicola in the HGC group were found to accumulate polyphosphate but not PHA. No
      cellular inclusions were detected in most members of the alpha-Proteobacteria and
      the Cytophaga-Flavobacterium group. The diversified functional traits observed
      suggested that different substrate metabolisms were used by predominant
      phylogenetic groups in EBPR processes.

PMID- 11321542
TI  - Bacterially mediated precipitation in marine stromatolites.
AB  - Stromatolites are laminated, lithified (CaCO3) sedimentary deposits formed by
      precipitation and/or sediment accretion by cyanobacterial-bacterial mat
      communities. Stromatolites have been associated with these communities as far
      back as the Precambrian era some 2+ billion years ago. The means by which
      microbial communities mediate the precipitation processes have remained unclear,
      and are the subject of considerable debate and speculation. Two alternative
      explanations for microbially mediated precipitation include: (i) cyanobacterial
      photosynthesis increases pH in a system supersaturated in respect of CaCO3,
      resulting in CaCO3 precipitation and then laminated lithification, and (ii)
      decomposition of cyanobacterial extracellular organic matter (e.g. sheaths,
      mucilage and organic acids) by microheterotrophs leads to release of organic
      bound Ca2+ ions and CaCO3 precipitation. We evaluated these explanations by
      examining metabolically active, lithifying stromatolitic mat communities from
      Highborne Cay, Bahamas, using microautoradiography. Microautoradiographic
      detection of 14CO2 fixation and 3H organic matter (D-glucose and an amino acid
      mixture) utilization by photosynthetically active cyanobacteria and
      microheterotrophs, combined with community-level uptake experiments, indicate
      that bacteria, rather than cyanobacteria are the dominant sites of CaCO3
      deposition. In the oligotrophic waters in which stromatolites exist,
      microheterotrophs are reliant on the photosynthetic community as a main source of
      organic matter. Therefore, autotrophic production indirectly controls microbially
      mediated precipitation and stromatolite formation in these shallow marine
      environments.

PMID- 11321543
TI  - Complete mineralization of dodecyldimethylamine using a two-membered bacterial
      culture.
AB  - Complete degradation of dodecyldimethylamine was achieved using a two-membered
      bacterial culture isolated from activated sludge. One member, identified as
      Burkholderia cepacia, was capable of degrading the alkyl chain of the molecule.
      The other member, identified as Stenotrophomonas maltophilia, was able to degrade
      dimethylamine, the product of the former. Batch culture experiments revealed that
      the two-membered culture consisting of B. cepacia and S. maltophilia was based on
      a commensalistic relationship under carbon-limited conditions. Under nitrogen
      limited conditions, the relationship of this culture was transformed from a
      commensalistic to a mutualistic one. A two-membered culture was therefore
      imperative for growth on dodecyldimethylamine under nitrogen-limited conditions,
      whereas a pure culture of B. cepacia was capable of growth on
      dodecyldimethylamine under carbon-limited conditions.

PMID- 11321545
TI  - Microbioal biofilms.

PMID- 11321544
TI  - Burkholderia cepacia complex: distribution of genomovars among isolates from the
      maize rhizosphere in Italy.
AB  - Burkholderia cepacia is a 'complex' in which seven genomic species or genomovars
      have so far been identified. It appears that all seven B. cepacia genomovars are
      capable of causing infections in vulnerable persons; in particular, the
      importance of Burkholderia multivorans (genomovar II) and B. cepacia genomovar
      III among cystic fibrosis isolates, especially epidemic ones, has been
      emphasized. In order to acquire a better comprehension of the genomovar
      composition of environmental populations of B. cepacia, 120 strains were isolated
      from the rhizosphere of maize plants cultivated in fields located in northern,
      central and southern Italy. The identification of the different genomovars was
      accomplished by a combination of molecular polymerase chain reaction (PCR)-based
      techniques, such as restriction fragment length polymorphism (RFLP) analysis of
      16S rDNA (ARDRA), genomovar-specific PCR tests and RFLP analyses based on
      polymorphisms in the recA gene whole-cell protein electrophoresis. ARDRA analysis
      allowed us to distinguish between all B. cepacia genomovars except B. cepacia
      genomovar I, B. cepacia genomovar III and Burkholderia ambifaria (genomovar VII).
      The latter genomovars were differentiated by means of recA PCR tests and RFLP
      analyses. Among the rhizospheric isolates of B. cepacia, we found only B. cepacia
      genomovar I, B. cepacia genomovar III, Burkholderia vietnamiensis (genomovar V)
      and B. ambifaria. B. cepacia genomovars I and III and B. ambifaria were recovered
      from all three fields, whereas B. vietnamiensis was detected only in the
      population isolated from the field located in central Italy. Among strains
      isolated from northern and southern Italy, the most abundant genomovars were B.
      ambifaria and B. cepacia genomovar III respectively; in contrast, the population
      isolated in central Italy showed an even distribution of strains among
      genomovars. These results indicate that it is not possible to differentiate
      clinical and environmental strains, or pathogenic and non-pathogenic strains, of
      the B. cepacia complex simply on the basis of genomovar status, and that the
      environment may serve as a reservoir for B. cepacia genomovar III infections in
      vulnerable humans.

PMID- 11321546
TI  - BMRI-2, Rossendorf/Dresden, Germany (30 August - 1 September 2000).
AB  - Clearly, there is much left to be understood about microbial processes and
      interactions with metals, but much progress has been made, and the
      multidisciplinary approach of groups who are studying both the microbial
      populations and the chemistry of biotransformations of metals by bacteria will
      ensure rapid progress in our understanding of these issues. Several major points
      from different speakers summarize this meeting and are usefully reiterated at
      this point: Toxic metal ions, unlike organic pollutants, are immutable, and their
      bioavailability is a critical feature of their toxicity. The mobility, transport
      and fate of toxic metals and radionuclides in the environment are dependent on
      chemical and geochemical processes in which micro-organisms are intimately
      involved. Metals can be mobilized as well as immobilized by microorganisms.
      Metal/radionuclide valencies and chemical properties are critical to their
      environmental mobility. Bacterial- or fungal-metal interactions will be
      complicated by the presence of other pollutants. The identification of bacteria
      from environmental samples should not rely on one methodology, as these have been
      shown to be biased. Sonja Selenska-Pobell organized both BMRI-1 in 1998 and BMRI
      2, which had well over 100 participants from Europe, Russia, USA and Japan in
      attendance. Thirty-one oral presentations were given, and over 30 posters were
      displayed over two poster sessions. BMRI-3 is provisionally planned for 2002 at
      GBF, Braunschweig, Germany.

PMID- 11321547
TI  - Chemical properties of catechols and their molecular modes of toxic action in
      cells, from microorganisms to mammals.
AB  - Catechols can undergo a variety of chemical reactions. In this review, we
      particularly focus on complex formations and the redox chemistry of catechols,
      which play an inportant role in the toxicity of catechols. In the presence of
      heavy metals, such as iron or copper, stable complexes can be formed. In the
      presence of oxidizing agents, catechols can be oxidized to semiquinone radicals
      and in a next step to o-benzoquinones. Heavy metals may catalyse redox reactions
      in which catechols are involved. Further chemical properties like the acidity
      constant and the lipophilicity of different catechols are shortly described as
      well. As a consequence of the chemical properties and the chemical reactions of
      catechols, many different reactions can occur with biomolecules such as DNA,
      proteins and membranes, ultimately leading to non-repairable damage. Reactions
      with nucleic acids such as adduct formation and strand breaks are discussed among
      others. Interactions with proteins causing protein and enzyme inactivation are
      described. The membrane-catechol interactions discussed here are lipid
      peroxidation and uncoupling. The deleterious effect of the interactions between
      catechols and the different biomolecules is discussed in the context of the
      observed toxicities, caused by catechols.

PMID- 11321548
TI  - Coexistence of a sulphate-reducing Desulfovibrio species and the dehalorespiring
      Desulfitobacterium frappieri TCE1 in defined chemostat cultures grown with
      various combinations of sulfate and tetrachloroethene.
AB  - A two-member co-culture consisting of the dehalorespiring Desulfitobacterium
      frappieri TCE1 and the sulphate-reducing Desulfovibrio sp. strain SULF1 was
      obtained via anaerobic enrichment from soil contaminated with tetrachloroethene
      (PCE). In this co-culture, PCE dechlorination to cis-dichloroethene was due to
      the activity of the dehalorespiring bacterium only. Chemostat experiments with
      lactate as the primary electron donor for both strains along with varying
      sulphate and PCE concentrations showed that the sulphate-reducing strain
      outnumbered the dehalogenating strain at relatively high ratios of sulphate/PCE.
      Stable co-cultures with both organisms present at similar cell densities were
      observed when both electron acceptors were supplied in the reservoir medium in
      nearly equimolar amounts. In the presence of low sulphate/PCE ratios, the
      Desulfitobacterium sp. became the numerically dominant strain within the
      chemostat co-culture. Surprisingly, in the absence of sulphate, strain SULF1 did
      not disappear completely from the co-culture despite the fact that there was no
      electron acceptor provided with the medium to be used by this sulphate reducer.
      Therefore, we propose a syntrophic association between the sulphate-reducing and
      the dehalorespiring bacteria via interspecies hydrogen transfer. The sulphate
      reducer was able to sustain growth in the chemostat co-culture by fermenting
      lactate and using the dehalogenating bacterium as a 'biological electron
      acceptor'. This is the first report describing growth of a sulphate-reducing
      bacterium in a defined two-member continuous culture by syntrophically coupling
      the electron and hydrogen transfer to a dehalorespiring bacterium.

PMID- 11321549
TI  - Foot-and-mouth disease: MAFF calls for more vets as the number of outbreaks
      continues to rise.

PMID- 11321550
TI  - Strategic decisions to evaluate before implementing a vaccine programme in the
      face of a foot-and-mouth disease (FMD) outbreak.

PMID- 11321551
TI  - Comparison of the measurement of total carbon dioxide and strong ion difference
      for the evaluation of metabolic acidosis in diarrhoeic calves.
AB  - Eighty-four calves with diarrhoea were treated with fluids and 13 apparently
      healthy calves of similar ages were sampled as controls. Their total blood carbon
      dioxide (TCO2) was measured with a Harleco apparatus and 31 of the calves were
      treated with oral fluids and 53 with parenteral fluids. The oral fluid contained
      118 mmol/litre Na+, 25 mmol/litre K+, 110 mmol/litre glucose, 108 mmol/litre
      bicarbonate (HCO3- as citrate), 43 mmol/litre Cl-, 4 mmol/litre Ca++, 4
      mmol/litre Mg++ and 20 mmol/litre glycine, and the parenteral fluid contained 144
      mmol/litre Na+, 4 mmol/litre K+, 35 mmol/litre HCO3- and 113 mmol/litre Cl-. Both
      treatments resulted in significant improvements in acid-base status as
      demonstrated by an increase in TCO2, and the treatment was successful in 27 of
      the 31 calves receiving oral fluids and in 45 of the 53 calves receiving
      parenteral fluids. Thirty-seven of the calves treated parenterally were very
      severely acidotic (TCO2 <8 mmol/litre) initially and they received an additional
      400 mmol HCO3- added to the first 5 litres of infusion. Treatment was successful
      in 33 of these calves. The decision to administer additional bicarbonate was made
      on the basis of their acid-base status as measured with a Harleco apparatus. The
      strong ion difference (Na++K+-Cl-) (SID) of the calves was calculated
      retrospectively. There was a significant correlation between the SID and TCO2 of
      the calves treated with oral fluids but not among the control calves or the
      calves treated parenterally. Furthermore, measurements of the change in SID
      during therapy gave little indication of the change in acid-base status as
      measured by the Harleco apparatus, with the SID decreasing (suggesting a
      worsening of acid-base status) in 16 calves in which the TCO2 increased
      (suggesting an improvement in acid-base status). There was a significant
      correlation between the change in SID and the change in TCO2 during treatment in
      the calves receiving oral fluids but not in the calves treated parenterally.

PMID- 11321552
TI  - Evaluation of fructosamine in dogs and cats with hypo- or hyperproteinaemia,
      azotaemia, hyperlipidaemia and hyperbilirubinaemia.
AB  - The influence of various pathological conditions on fructosamine levels in
      normoglycaemic dogs and cats was investigated. The most frequent and most
      pronounced deviations were found in animals with hypoproteinaemia, in which
      fructosamine was significantly lower than in the controls. In 66 per cent of the
      dogs and 67 per cent of the cats with hypoproteinaemia the levels were below the
      reference range. In the dogs the concentration of fructosamine was correlated
      with the level of albumin, but in the cats it was correlated with the level of
      total protein. Dogs with hyperlipidaemia and azotaemia also had significantly
      lower levels of fructosamine; 38 per cent of those with hyperlipidaemia and 47
      per cent of those with azotaemia had fructosamine levels outside the reference
      range. No significant changes in fructosamine were detected in dogs or cats with
      hyperproteinaemia or hyperbilirubinaemia, or in cats with hyperlipidaemia or
      azotaemia.

PMID- 11321553
TI  - Treatment of sepsis in the small tarsal joints of 11 horses with gentamicin
      impregnated polymethylmethacrylate beads.
AB  - Gentamicin-impregnated polymethylmethacrylate beads were used to treat infective
      arthritis in the small tarsal joints of 11 severely lame horses. Under general
      anaesthesia, between five and 10 beads were placed into a 7 to 8 mm tract drilled
      across the affected joint and, in all except one horse, they were left in place
      for 14 days. Two of the horses were euthanased for reasons other than persistent
      tarsal joint sepsis, but the other nine survived and seven of them returned to
      their previous level of athletic performance.

PMID- 11321554
TI  - Useful signs for the diagnosis of cystic ovaries in cattle.

PMID- 11321555
TI  - Elaphostrongylus cervi infection in a Swiss goat.

PMID- 11321556
TI  - Foot-and-mouth disease: appeal for more veterinarians.

PMID- 11321557
TI  - Foot-and-mouth disease: appeal for more veterinarians.

PMID- 11321558
TI  - Foot-and-mouth disease: appeal for more veterinarians.

PMID- 11321559
TI  - Foot-and-mouth disease control measures.

PMID- 11321561
TI  - VN training scheme.

PMID- 11321560
TI  - PMWS and PDNS in Great Britain.

PMID- 11321562
TI  - VN training scheme.

PMID- 11321563
TI  - Veterinary pharmacy.

PMID- 11321564
TI  - Vaccination certificates for cat shows.

PMID- 11321565
TI  - Microbial multidrug efflux: introduction.

PMID- 11321566
TI  - Comparative genomics of microbial drug efflux systems.
AB  - The complete genome sequences of 36 microorganisms have now been published and
      this wealth of genome data has enabled the development of comparative genomic and
      functional genomic approaches to investigate the biology of these organisms.
      Comparative genomic analyses of membrane transport systems have revealed that
      transporter substrate specificities correlate with an organism's lifestyle. The
      types and numbers of predicted drug efflux systems vary dramatically amongst
      sequenced organisms. Microarray and gene knockout studies to date have suggested
      that predicted drug efflux genes often appear to be a) non-essential and b)
      expressed at detectable levels under standard laboratory growth conditions.

PMID- 11321567
TI  - The ostensible paradox of multidrug recognition.
AB  - The ability of multidrug-efflux transporters to recognize scores of dissimilar
      organic compounds has always been considered paradoxical because of its apparent
      contradiction to some of the basic dogmas of biochemistry. In order to
      understand, at least in principle, how a protein can recognize multiple
      compounds, we analysed the transcriptional regulator of the Bacillus subtilis
      multidrug transporter Bmr. This regulator, BmrR, binds multiple dissimilar
      hydrophobic cations and, by activating expression of the Bmr transporter, causes
      their expulsion from the cell. Crystallographic analysis of the complexes of the
      inducer-binding domain of BmrR with some of its inducers revealed that ligands
      penetrate the hydrophobic core of the protein, where they form multiple van der
      Waals and stacking interactions with hydrophobic amino acids and an electrostatic
      bond with the buried glutamate. Mutational analysis of the binding site suggests
      that each ligand forms a unique set of atomic contacts with the protein: each
      tested mutation exerted disparate effects on the binding of different ligands.
      The example of BmrR demonstrates that a protein can bind multiple hydrophobic
      compounds with micromolar affinities by using only electrostatic and hydrophobic
      interactions. Its ligand specificity can be further broadened by the flexibility
      of the binding site. It appears, therefore, that the commonly expressed
      fascination with the relaxed substrate specificity of multidrug transporters is
      misdirected and originates from an almost exclusive familiarity with the more
      sophisticated processes of specific molecular recognition that predominate among
      proteins analyzed to date.

PMID- 11321568
TI  - Precious things come in little packages.
AB  - The 110-amino acid multidrug transporter from E. coli, EmrE, is a member of the
      family of MiniTexan or Smr drug transporters. EmrE can transport acriflavine,
      ethidium bromide, tetraphenylphosphonium (TPP+), benzalkonium and several other
      drugs with relatively high affinities. EmrE is an H+/drug antiporter, utilizing
      the proton electrochemical gradient generated across the bacterial cytoplasmic
      membrane by exchanging two protons with one substrate molecule. The EmrE
      multidrug transporter is unique in its small size and hydrophobic nature.
      Hydropathic analysis of the EmrE sequence predicts four alpha-helical
      transmembrane segments. This model is experimentally supported by FTIR studies
      that confirm the high alpha-helicity of the protein and by high-resolution
      heteronuclear NMR analysis of the protein structure. The TMS of EmrE are tightly
      packed in the membrane without any continuous aqueous domain, as was shown by
      Cysteine scanning experiments. These results suggest the existence of a
      hydrophobic pathway through which the substrates are translocated. EmrE is
      functional as a homo-oligomer as suggested by several lines of evidence,
      including co-reconstitution experiments of wild-type protein with inactive
      mutants in which negative dominance has been observed. EmrE has only one membrane
      embedded charged residue, Glu-14, that is conserved in more than fifty homologous
      proteins and it is a simple model system to study the role of carboxylic residues
      in ion-coupled transporters. We have used mutagenesis and chemical modification
      to show that Glu-14 is part of the substrate-binding site. Its role in proton
      binding and translocation was shown by a study of the effect of pH on ligand
      binding, uptake, efflux and exchange reactions. We conclude that Glu-14 is an
      essential part of a binding site, common to substrates and protons. The occupancy
      of this site is mutually exclusive and provides the basis of the simplest
      coupling of two fluxes. Because of some of its properties and its size, EmrE
      provides a unique system to understand mechanisms of substrate recognition and
      translocation.

PMID- 11321569
TI  - Staphylococcal multidrug efflux protein QacA.
AB  - The QacA multidrug exporter from Staphylococcus aureus mediates resistance to a
      wide array of monovalent or divalent cationic, lipophilic, antimicrobial
      compounds. QacA provides resistance to these various compounds via a proton
      motive force-dependent antiport mechanism that conforms to classical Michaelis
      Menten kinetics. Fluorescent transport analyses have demonstrated that this
      QacA:substrate interaction occurs with high affinity and competition studies have
      shown that QacA-mediated ethidium export is competitively inhibited by other
      monovalent cations, and non-competitively inhibited by divalent cations,
      suggesting that monovalent and divalent cations bind at distinct sites on the
      QacA protein. The closely related export protein QacB, mediates lower levels of
      resistance to divalent cations, and lacks a high affinity-binding site for
      divalent cations. The cell membrane has been identified as the origin of QacA
      mediated efflux; substrates are bound and expelled from within this hydrophobic
      environment. Regulation of qacA expression is achieved via the transacting
      repressor protein, QacR. QacR belongs to the TetR family of transcriptional
      repressor proteins, which all possess a helix-turn-helix DNA-binding domain at
      their N-terminal ends, and have highly divergent C-termini postulated to be
      involved in the binding of inducing compounds. QacR specifically binds to an
      inverted repeat, IR1, which has been identified as the qacA operator region, and
      overlaps the identified promoter sequence for qacA. QacR, like the multidrug
      export protein whose expression it regulates, has been shown to interact directly
      with a number of structurally-dissimilar compounds.

PMID- 11321570
TI  - MdfA, an interesting model protein for studying multidrug transport.
AB  - The resistance of cells to many drugs simultaneously (multidrug resistance) often
      involves the expression of membrane transporters (Mdrs); each can recognize and
      expel a broad spectrum of chemically unrelated drugs from the cell. Despite
      extensive research for many years, the actual mechanism of multidrug transport is
      still largely unknown. In addition to general questions dealing with energy
      coupling, the molecular view of substrate recognition by Mdrs is generally
      obscure. This mini-review describes structural and functional properties of the
      Escherichia coli Mdr, MdfA, and discusses the possibility that this transporter
      may serve as a model for studying the multidrug recognition phenomenon and the
      mechanism of multidrug transport.

PMID- 11321571
TI  - Enterococcus faecalis multi-drug resistance transporters: application for
      antibiotic discovery.
AB  - Using bioinformatics approaches, 34 potential multidrug resistance (MDR)
      transporter sequences representing 4 different transporter families were
      identified in the unannotated Enterococcus faecalis database (TIGR). A functional
      genomics campaign generating single-gene insertional disruptions revealed several
      genes whose absence confers significant hypersensitivities to known
      antimicrobials. We constructed specific strains, disrupted in a variety of
      previously unpublished, putative MDR transporter genes, as tools to improve the
      success of whole-cell antimicrobial screening and discovery. Each of the
      potential transporters was inactivated at the gene level and then phenotypically
      characterized, both with single disruption mutants and with 2-gene mutants built
      upon a delta norA deleted strain background.

PMID- 11321572
TI  - Molecular basis of multidrug transport by ATP-binding cassette transporters: a
      proposed two-cylinder engine model.
AB  - ATP-binding cassette multidrug transporters are probably present in all living
      cells, and are able to export a variety of structurally unrelated compounds at
      the expense of ATP hydrolysis. The elevated expression of these proteins in
      multidrug resistant cells interferes with the drug-based control of cancers and
      infectious pathogenic microorganisms. Multidrug transporters interact directly
      with the drug substrates. Insights into the structural elements in drug molecules
      and transport proteins that are required for this interaction are now beginning
      to emerge. However, much remains to be learned about the nature and number of
      drug binding sites in the transporters, and the mechanism(s) by which ATP
      hydrolysis is coupled to changes in affinity and/or accessibility of drug binding
      sites. This review summarizes recent advances in answering these questions for
      the human multidrug resistance P-glycoprotein and its prokaryotic homolog LmrA.
      The relevance of these findings for other ATP-binding cassette transporters will
      be discussed.

PMID- 11321573
TI  - Prokaryote multidrug efflux proteins of the major facilitator superfamily:
      amplified expression, purification and characterisation.
AB  - In bacterial genomes 3-12% of open reading frames are predicted to encode
      membrane transport proteins. These proteins can be vital for antibiotic efflux,
      protein/ toxin secretion, cell nutrition, environmental sensing, ATP synthesis,
      and other functions. Some, such as the multidrug efflux proteins, are potential
      targets for the development of new antibacterials and also for applications in
      biotechnology. In general membrane transport proteins are poorly understood,
      because of the technical difficulties involved in isolating sufficient protein
      for elucidation of their structure-activity relationships. We describe a general
      strategy for the amplified expression, purification and characterisation of
      prokaryotic multidrug efflux proteins of the 'Major facilitator superfamily' of
      transport proteins, using the Bacillus subtilis multidrug resistance protein,
      'Bmr', as example.

PMID- 11321574
TI  - Multidrug resistance and ABC transporters in parasitic protozoa.
AB  - Drug resistance is an important problem in parasitic protozoa. We review here the
      role of ABC transporters in drug resistance in parasites. We have concentrated on
      gene and gene products for which there is a strong evidence for their role in
      resistance.

PMID- 11321575
TI  - The pleitropic drug ABC transporters from Saccharomyces cerevisiae.
AB  - The Saccharomyces cerevisiae genome contains 16 genes encoding full-size ABC
      transporters. Each comprises two nucleotide binding folds (NBF) alternating with
      transmembrane domains (TM). We have studied in detail three plasma membrane
      multidrug exporters: Pdr5p (TC3.A.1.205.1) and Snq2p (TC3.A.1.205.2) which share
      NBF-TM-NBF-TM topology as well as Yor1p (TC3.A.1.208.3) which exhibits the
      reciprocal TM-NBF-TM-NBF topology. The substrate specificity of Pdr5p, Snq2p and
      Yor1p are largely, but not totally, overlapping as shown by screening the growth
      inhibition by 349 toxic compounds of combinatorial deletants of these three ABC
      genes. Multiple deletion of 7 ABC genes (YOR1, SNQ2, PDR5, YCF1, PDR10, PDR11 and
      PDR15) and of two transcription activation factors (PDR1 and PDR3) renders the
      cell from 2 to 200 times more sensitive to numerous toxic coumpounds including
      antifungals used in agriculture or medicine. The use of the pdr1-3 activating
      mutation and when necessary of the PDR5 promoter in appropriate multideleted
      hosts allow high levels of expression of Pdr5p, Snq2p or Yor1 p. These
      overexpressed proteins exhibit ATPase activity in vitro and confer considerable
      multiple drug resistance in vivo. The latter property can be used for screening
      specific inhibitors of fungal and other ABC transporters.

PMID- 11321576
TI  - AcrAB and related multidrug efflux pumps of Escherichia coli.
AB  - The AcrAB system of Escherichia coli is a multidrug efflux system composed of an
      RND-type transporter AcrB and a periplasmic accessory protein AcrA, and pumps out
      a wide variety of lipophilic and amphiphilic inhibitors directly into the medium,
      presumably through the TolC outer membrane channel. AcrA, a highly elongated
      protein, is thought to bring the outer and inner membranes closer. It forms a
      trimer that interacts with a monomeric AcrB, which was shown by in vitro
      reconstitution to be a proton antiporter. Details of interaction between the

PMID- 11321577
TI  - Genetic organization and regulation of antimicrobial efflux systems possessed by
      Neisseria gonorrhoeae and Neisseria meningitidis.
AB  - Efflux pumps can make a significant contribution to the capacity of bacteria to
      resist the action of antibiotics. Certain efflux pumps also recognize
      antimicrobial agents that are present in their respective hosts and their ability
      to export toxic agents could enhance bacterial survival during infection prior to
      appearance of cellular or humoral host defensive systems. This review is
      concerned with the principal efflux pumps possessed by two closely related strict
      human pathogens, Neisseria gonorrhoeae and Neisseria meningitidis. Specific
      emphasis is placed on the organization of the structural genes encoding the mtr
      and far efflux pumps, the substrates (often host-derived) recognized by these
      pumps, and the cis- and trans-acting transcriptional factors that regulate efflux
      pump gene expression in gonococci and meningococci. The overriding theme of this
      review is that the efflux pumps possessed by these pathogens likely contribute to
      their pathogenic mechanisms by providing a means to escape a number of
      antimicrobial compounds that bathe mucosal surfaces.

PMID- 11321578
TI  - Inhibition of efflux pumps as a novel approach to combat drug resistance in
      bacteria.
AB  - Efflux mechanisms have become broadly recognized as major components of
      resistance to many classes of antibiotics. Some efflux pumps selectively extrude
      specific antibiotics, while others, referred to as multidrug resistance (MDR)
      pumps, expel a variety of structurally diverse compounds with differing
      antibacterial modes of action. There are numerous potentially beneficial
      consequences of the inhibition of efflux pumps in improving the clinical
      performance of various antibiotics, and several companies and research
      laboratories have initiated programs to discover and develop efflux pump
      inhibitors. This review will summarize recent achievements in this new, very
      exciting and equally challenging field.

PMID- 11321579
TI  - Functions of tetracycline efflux proteins that do not involve tetracycline.
AB  - Tet(L) and Tet(K) are specific antibiotic-resistance determinants. They catalyze
      efflux of a tetracycline(Tc)-divalent metal complex in exchange for protons, as
      do other Tet efflux proteins. These Tet proteins also catalyze Na+ and K+
      exchange for protons. Each of the "cytoplasmic substrates", Na+, K+ and the Tc
      metal ion complex, can also be exchanged for K+, a catalytic mode that accounts
      for the long-recognized K+ uptake capacity conferred by some Tet proteins. The
      multiple catalytic modes of Tet(L) and Tet(K) provide potential new avenues for
      development of inhibitors of these efflux systems as well as avenues for
      exploration of structure-function relationships. The multiple catalytic modes of
      Tet(L), which is chromosomally encoded in Bacillus subtilis, also correspond to
      diverse physiological roles, including roles in antibiotic-, Na+-, and alkali
      resistance as well as K+ acquisition. The use of K+ as an external coupling ion
      may contribute not only to the organism's K+ uptake capacity but also to its
      ability to exclude Na+ and Tc at elevated pH values. Regulation of the
      chromosomal tetL gene by Tc has been proposed to involve a translational re
      initiation mechanism that is novel for an antibiotic-resistance gene and
      increases Tet expression seven-fold. Other elements of tetL expression and its
      regulation are already evident, including gene amplification and use of multiple
      promoters. However, further studies are required to clarify the full panoply of
      regulatory mechanisms, and their integration to ensure different levels of tetL
      expression that are optimal for its different functions. It will also be of
      interest to investigate the implications of Tet(L) and Tet(K) multifunctionality
      on the emergence and persistence of these antibiotic-resistance genes.

PMID- 11321580
TI  - In search of natural substrates and inhibitors of MDR pumps.
AB  - The function of microbial MDRs remains a hotly debated subject. Given the very
      broad substrate specificities of some MDRs, like the RND pumps that can extrude
      all classes of amphipathic compounds (cationic, neutral, and anionic), it seems
      difficult to develop a rationale for pinpointing possible natural substrates of
      these translocases. At the same time, several clues can be used to guide our
      search for natural MDR substrates. One is the fact that amphipathic cations
      appear to be the preferred substrates of MDRs. These substances are extruded by
      MDRs of all 5 known families and are the almost exclusive substrates of SMR and
      MF family MDRs. The universal nature of amphipathic cations as MDR substrates
      suggests that these were the substances that fueled the evolution of MDR pumps.
      Two factors apparently favored this particular class of molecules for the role of
      original MDR substrates--need and opportunity. Unlike other substances,
      amphipathic cations accumulate in the cell driven by the membrane potential,
      which makes cations potentially the most dangerous toxins. At the same time,
      amphipathic cations are highly hydrated and do not permeate the membrane as
      readily as neutral compounds, making it feasible to design a defense based on an
      efflux pump. The paucity of known cationic (non-basic) antimicrobials might be a
      result of using MDR-expressing microbial cells for antibiotic discovery. Plant
      amphipathic cations, the berberine alkaloids, are good MDR substrates. The
      Berberis plants produce 5'-methoxyhydnocarpin-D, an MDR inhibitor that
      potentiates the action of berberine. It is suggested that the further evolution
      of MDR pumps was determined largely by the barrier function of the membrane they
      reside in. Thus Gram negative bacteria have an outer membrane barrier that slows
      the penetration of virtually all amphipathic molecules, and transenvelope MDRs of
      the RND and EmrAB-type extrude their substrates across this barrier. A low
      permeability of the cytoplasmic membrane of yeast similarly allows for the
      operation of broad-specificity ABC and MF MDRs. The presence of MDR sensors that
      regulate the expression of some MDR pumps strongly suggests that defense against
      external toxins is the function of these MDRs. The BmrR transcriptional activator
      of the MerR family induces expression of the Bmr pump in B. subtilis and is a
      sensor specifically designed to recognize amphipathic cations. Similarly, the
      OacR repressor binds chemically unrelated cations, which leads to the expression
      of the QacA pump in S. aureus. In E. coli, the EmrR sensor of the MarR repressor
      family binds unrelated neutral molecules, allowing for expression of the
      transenvelope EmrAB pump.

PMID- 11321581
TI  - Multidrug efflux pumps and antimicrobial resistance in Pseudomonas aeruginosa and
      related organisms.
AB  - Pseudomonas aeruginosa is an opportunistic human pathogen characterized by an
      innate resistance to multiple antimicrobial agents. A major contribution to this
      intrinsic multidrug resistance is provided by a number of broadly-specific
      multidrug efflux systems, including MexAB-OprM and MexXY-OprM. In addition, these
      and two additional tripartite efflux systems, MexCD-OprJ and MexEF-OprN, promote
      acquired multidrug resistance as a result of mutational hyperexpression of the
      efflux genes. In addition to antibiotics, these pumps promote export of numerous
      dyes, detergents, inhibitors, disinfectants, organic solvents and homoserine
      lactones involved in quorum sensing. The efflux pump proteins are highly
      homologous and consist of a cytoplasmic membrane-associated drug-proton
      antiporter of the Resistance-Nodulation-Division (RND) family, an outer membrane
      channel-forming protein [sometimes called outer membrane factor (OMF)] and a
      periplasmic membrane fusion protein (MFP). Homologues of these systems have been
      described in Stenotrophomonas maltophilia, Burkholderia cepacia, Burkholderia
      pseudomallei and the non-pathogen Pseudomonas putida, where they play a role in
      export of and resistance to multiple antimicrobial agents and/or organic
      solvents. Although the natural function of these multidrug efflux systems is
      largely unknown, their contribution to antibiotic resistance and their
      conservation in a number of important human pathogens makes them logical targets
      for therapeutic intervention.

PMID- 11321582
TI  - Practical mechanisms for interrupting the oral-fecal lifecycle of Escherichia
      coli.
AB  - Escherichia coli is a common gut inhabitant, but it is usually out numbered by
      strictly anaerobic bacteria. When fecal material is exposed to oxygen,
      fermentation acids can be respired, and E. coli numbers increase. E. coli can
      survive for long periods of time in feces, but subsequent proliferation is
      dependent on its ability to re-enter the gastrointestinal tract via contaminated
      water and food. The oral-fecal lifestyle of E. coli is facilitated by its ability
      to survive the low pH of the human gastric stomach. Most strains of E. coli do
      not cause human disease, but some strains produce toxins and other virulence
      factors. Mature cattle carry E. coli O157:H7 without showing signs of infection,
      and beef can be contaminated with cattle feces at slaughter. Cattle manure is
      often used as a fertilizer by the vegetable industry, and E. coli from manure can
      migrate through the soil into water supplies. Sanitation, cooking and
      chlorination have been used to combat fecal E. coli, but these methods are not
      always effective. Recent work indicates that cattle diets can be modified
      overcome the extreme acid resistance of E. coli. When cattle were fed have for
      only a few days, colonic volatile fatty acid concentrations declined, pH
      increased, and the E. coli were no longer able to survive a pH shock that
      mimicked the human gastric stomach. E. coli in stored cattle manure eventually
      become highly acid resistant even if the cattle were fed hay, but these bacteria
      could be killed by sodium carbonate (150 mM, pH 8.5). Because the diet
      manipulations and carbonate treatments affected E. coli in general rather than
      specific serotypes, there is an increased likelihood of successful field
      application.

PMID- 11321583
TI  - The diheme cytochrome b subunit (Narl) of Escherichia coli nitrate reductase A
      (NarGHI): structure, function, and interaction with quinols.
AB  - Significant recent advances have been made in studies of the major dissimilatory
      nitrate reductase (NarGHI) of Escherichia coli. This enzyme is a complex iron
      sulfur ([Fe-S]) molybdoenzyme that oxidizes menaquinol or ubiquinol at a
      periplasmically oriented Q-site (Qp site), and reduces nitrate at a
      cytoplasmically-oriented molybdo-(bismolybdopterin guanine dinucleotide) (Mo
      bisMGD) cofactor. The Qp site, as well as two hemes, termed bL and bH, are
      localized in a hydrophobic diheme cytochrome b(Narl) that: (i) provides a conduit
      for electron-transfer from the periplasmically-oriented Qp-site; (ii) provides a
      membrane anchoring functionality for the membrane-extrinsic subunits (NarGH) that
      coordinate the Mo-bisMGD (NarG) and four [Fe-S] clusters (NarH); and (iii) helps
      ensure the separation of sites of H+-yielding and H+-consuming reactions such
      that enzyme turnover leads to the generation of a proton-electrochemical
      potential across the cytoplasmic membrane. This minireview focuses on recent
      advances and future prospects for the diheme cytochrome b subunit (Narl) of
      NarGHI.

PMID- 11321584
TI  - A web-based program for the prediction of average hydropathy, average
      amphipathicity and average similarity of multiply aligned homologous proteins.
AB  - We designed a web-based program, AveHAS, to determine and plot the average
      hydropathy, average amphipathicity and average similarity for a clustal X-derived
      multiple alignment of homologous protein sequences. This method is based on the
      TREEMOMENT and Hydro programs. It has a user-friendly interface, a convenient
      input format and an improved algorithm.

PMID- 11321585
TI  - SigB, SigC, and SigE from Myxococcus xanthus homologous to sigma32 are not
      required for heat shock response but for multicellular differentiation.
AB  - Myxococcus xanthus has been known to have multiple sigma factors which are
      considered to play important roles in regulation of gene expression in
      development. A new gene encoding a putative sigma factor, sigE, was cloned by
      using a degenerate oligonucleotide corresponding to the conserved region 2.2 of
      M. xanthus SigA. In the 2.0-kb nucleotide sequence, an open reading frame
      consisting of 280 amino acid residues was identified. The amino acid sequence of
      SigE shows high similarity to heat shock sigma factors in bacteria. However, the
      sigE gene is not induced by heat shock and deletion of sigE does not affect
      production of heat shock proteins. SigE is expressed during both vegetative
      growth and fruiting body development. In the deletion mutant of the sigE gene
      fruiting body formation is initiated earlier and fewer spores are produced than
      in the parent strain. Interestingly, the deltasigE mutant shows defects in
      fruiting body formation at 37 degrees C. In addition to SigE, SigB and SigC show
      high sequence similarity to heat shock sigma factors. However, even if all three
      sigma factor genes are disrupted, heat shock proteins are still normally induced.
      A deltasigBdeltasigCdeltasigE triple deletion strain forms fruiting bodies
      earlier, but sporulats later than the parent strain. Spores from the triple
      deletion mutant are aberrant and their viability is less than 0.001% compared
      with that of the parent strain, suggesting that these sigma factors may have
      redundant functions in multicellular differentiation of M. xanthus.

PMID- 11321586
TI  - Pyruvate carboxylase is a major bottleneck for glutamate and lysine production by
      Corynebacterium glutamicum.
AB  - Corynebacterium glutamicum possesses both phosphoenolpyruvate carboxylase (PEPCx)
      and pyruvate carboxylase (PCx) as anaplerotic enzymes for growth on
      carbohydrates. To analyze the significance of PCx for the amino acid production
      by this organism, the wild-type pyc gene, encoding PCx, was used for the
      construction of defined pyc-inactive and pyc-overexpressing strains and the
      glutamate, lysine and threonine production capabilities of these recombinant
      strains of C. glutamicum were tested in comparison to the respective host
      strains. No PCx activity was observed in the pyc-inactive mutants whereas the pyc
      overexpressing strains showed eight-to elevenfold higher specific PCx activity
      when compared to the host strains. In a detergent-dependent glutamate production
      assay, the pyc-overexpressing strain showed more than sevenfold higher, the PCx
      deficient strain about twofold lower glutamate production than the wild-type.
      Overexpression of the pyc gene and thus increasing the PCx activity in a lysine
      producing strain of C. glutamicum resulted in approximately 50% higher lysine
      accumulation in the culture supernatant whereas inactivation of the pyc gene led
      to a decrease by 60%. In a threonine-producing strain of C. glutamicum, the
      overexpression of the pyc gene led to an only 10 to 20% increase in threonine
      production, however, to a more than 150% increase in the production of the
      threonine precursor homoserine. These results identify the anaplerotic PCx
      reaction as a major bottleneck for amino acid production by C. glutamicum and
      show that the enzyme is an important target for the molecular breeding of
      hyperproducing strains.

PMID- 11321587
TI  - Expression and isolation of antimicrobial small molecules from soil DNA
      libraries.
AB  - Natural products have been a critically important source of clinically relevant
      small molecule therapeutics. However, the discovery rate of novel structural
      classes of antimicrobial molecules has declined. Recently, increasing evidence
      has shown that the number of species cultivated from soil represents less than 1%
      of the total population, opening up the exciting possibility that these
      uncultured species may provide a large untapped pool from which novel natural
      products can be discovered. We have constructed and expressed in E. coli a BAC
      (bacterial artificial chromosome) library containing genomic fragments of DNA (5
      120kb) isolated directly from soil organisms (S-DNA). Screening of the library
      resulted in the identification of several antimicrobial activities expressed by
      different recombinant clones. One clone (mg1.1) has been partially characterized
      and found to express several small molecules related to and including indirubin.
      These results show that genes involved in natural product synthesis can be cloned
      directly from S-DNA and expressed in a heterologous host, supporting the idea
      that this technology has the potential to provide novel natural products from the
      wealth of environmental microbial diversity and is a potentially important new
      tool for drug discovery.

PMID- 11321588
TI  - The PecM protein of the phytopathogenic bacterium Erwinia chrysanthemi, membrane
      topology and possible involvement in the efflux of the blue pigment indigoidine.
AB  - The pecS regulatory locus negatively modulates the expression of many virulence
      genes in Erwinia chrysanthemi. This locus consists of two genes, pecS and pecM,
      divergently transcribed. Previous studies have shown that PecS down-regulates the
      expression of both pecSand pecMgenes and that PecM is required for full PecS
      activity. Computer-aided hydropathy analysis of PecM predicted the presence of
      between 8 to 10 potential transmembrane segments. We analyzed the membrane
      topology of PecM using the beta-lactamase gene fusion system and obtained the
      following unique characteristics. PecM contains 10 membrane spanning segments,
      with both the amino and carboxyl termini located in the cytoplasmic side of the
      inner membrane. The fourth periplasmic loop, which has a relatively long
      hydrophilic domain containing 17 amino acid residues, may play an important role
      in PecM function. The topological model obtained for PecM can be applied to PecM
      homologues in other bacteria. Measurement of the extrusion of the blue pigment
      indigoidine by the E. chrysanthemi derivative isogenic mutants pecS, pecM and
      pecS-pecM revealed that PecM is required for complete efflux of the pigment. Its
      relation to other efflux systems and its potential physiological role are
      discussed.

PMID- 11321589
TI  - Comparative approach to analysis of regulation in complete genomes: multidrug
      resistance systems in gamma-proteobacteria.
AB  - Comparative approach is a powerful tool for analysis of gene regulation in
      bacterial genomes. Here we apply it to analysis of regulation of the multidrug
      resistance transport (MDRT) systems in enterobacteria Escherichia coli,
      Salmonella typhi, Klebsiella pneumoniae and Yersinia pestis. Comparison of
      nucleotide sequences upstream of MDRT genes was performed in order to predict new
      regulatory sites (operators) and identify candidate regulons. Since the
      regulatory sites diverge slower than the non-coding regions in general, they are
      visible as strongly conserved islands. This analysis resulted in description of a
      regulatory network for known and hypothetical MDRT systems and porins. New
      candidate members of the MarA regulon were detected. Putative binding sites for
      EmrR and AcrR were suggested. A new hypothetical MarX regulon was described that
      includes some multidrug transporters and porins.

PMID- 11321590
TI  - Microwave image reconstruction utilizing log-magnitude and unwrapped phase to
      improve high-contrast object recovery.
AB  - Reconstructing images of large high-contrast objects with microwave methods has
      proved difficult. Successful images have generally been obtained by using a
      priori information to constrain the image reconstruction to recover the correct
      electromagnetic property distribution. In these situations, the measured electric
      field phases as a function of receiver position around the periphery of the
      imaging field-of-view vary rapidly often undergoing changes of greater than pi
      radians especially when the object contrast and illumination frequency increase.
      In this paper, we introduce a modified form of a Maxwell equation model-based
      image reconstruction algorithm which directly incorporates log-magnitude and
      phase of the measured electric field data. By doing so, measured phase variation
      can be unwrapped and distributed over more than one Rieman sheet in the complex
      plane. Simulation studies and microwave imaging experiments demonstrate that
      significant image quality enhancements occur with this approach for large high
      contrast objects. Simple strategies for visualizing and unwrapping phase values
      as a function of the transmitter and receiver positions within our microwave
      imaging array are described. Metrics of the degree of phase variation expressed
      in terms of the amount and extent of phase wrapping are defined and found to be
      figures-of-merit which estimate when it is critical to deploy the new image
      reconstruction approach. In these cases, the new algorithm recovers high-quality
      images without resorting to the use of a priori information on object contrast
      and/or size as previously required.

PMID- 11321591
TI  - Vessel extraction in medical images by wave-propagation and traceback.
AB  - This paper presents an approach for the extraction of vasculature from
      angiography images by using a wave propagation and traceback mechanism. We
      discuss both the theory and the implementation of the approach. Using a dual
      sigmoidal filter, we label each pixel in an angiogram with the likelihood that it
      is within a vessel. Representing the reciprocal of this likelihood image as an
      array of refractive indexes, we propagate a digital wave through the image from
      the base of the vascular tree. This wave "washes" over the vasculature, ignoring
      local noise perturbations. The extraction of the vasculature becomes that of
      tracing the wave along the local normals to the waveform. While the approach is
      inherently single instruction stream multiple data stream (SIMD), we present an
      efficient sequential algorithm for the wave propagation and discuss the traceback
      algorithm. We demonstrate the effectiveness of our integer image neighborhood
      based algorithm and its robustness to image noise.

PMID- 11321592
TI  - Realizations of fast 2-D/3-D image filtering and enhancement.
AB  - This paper proposes a novel algorithm for multidimensional image enhancement
      based on a fuzzy domain enhancement method, and an implementation of a recursive
      and separable low-pass filter. Considering a smoothed image as a fuzzy data set,
      each pixel in an image is processed independently, using fuzzy domain
      transformation and enhancement of both the dynamic range and the local gray level
      variations. The algorithm has the advantages of being fast and adaptive, so it
      can be used in real-time image processing applications and for multidimensional
      data with low computational cost. It also has the ability to reduce noise and
      unwanted background that may affect the visualization quality of two-dimensional
      (2-D)/three-dimensional (3-D) data. Examples for the applications of the
      algorithm are given for mammograms, ultrasound 3-D images, and photographic
      images.

PMID- 11321593
TI  - Anisotropic 2-D and 3-D averaging of fMRI signals.
AB  - A novel method for denoising functional magnetic resonance imaging temporal
      signals is presented in this note. The method is based on progressively enhancing
      the temporal signal by means of adaptive anisotropic spatial averaging. This
      average is based on a new metric for comparing temporal signals corresponding to
      active fMRI regions. Examples are presented both for simulated and real two and
      three-dimensional data. The software implementing the proposed technique is
      publicly available for the research community.

PMID- 11321594
TI  - Tag surface reconstruction and tracking of myocardial beads from SPAMM-MRI with
      parametric B-spline surfaces.
AB  - Magnetic resonance imaging (MRI) is unique in its ability to noninvasively and
      selectively alter tissue magnetization, and create tag planes intersecting image
      slices. The resulting grid of signal voids allows for tracking deformations of
      tissues in otherwise homogeneous-signal myocardial regions. In this paper, we
      propose a specific spatial modulation of magnetization (SPAMM) imaging protocol
      together with efficient techniques for measurement of three-dimensional (3-D)
      motion of material points of the human heart (referred to as myocardial beads)
      from images collected with the SPAMM method. The techniques make use of tagged
      images in orthogonal views by explicitly reconstructing 3-D B-spline surface
      representation of tag planes (tag planes in two orthogonal orientations
      intersecting the short-axis (SA) image slices and tag planes in an orientation
      orthogonal to the short-axis tag planes intersecting long-axis (LA) image
      slices). The developed methods allow for viewing deformations of 3-D tag
      surfaces, spatial correspondence of long-axis and short-axis image slice and tag
      positions, as well as nonrigid movement of myocardial beads as a function of
      time.

PMID- 11321595
TI  - A novel missense mutation of the CBFA1 gene in a family with cleidocranial
      dysplasia (CCD) and variable expressivity.
AB  - The aim of this study was to analyze the CBFA1 gene in a phenotypically variable
      family with autosomal dominant cleidocranial dysplasia (CCD). Five members of a
      family with CCD were characterized clinically. X-rays and photographs of the two
      clinically affected family members were taken. The genotype of all five affected
      family members was determined with the use of single strand conformation
      polymorphism (SSCP) and direct sequencing. A point-mutation in exon 2 (R148G) was
      detected in a patient with the full-blown clinical phenotype. His son,
      demonstrating the same mutation, showed only the dental CCD characteristics. No
      mutation could be found in the three clinically healthy family members. To
      conclude, a missense mutation in the CBFA1 gene was detected in a family with
      variably expressed CCD syndrome. A detailed clinical examination is necessary to
      detect minimally affected gene mutation carriers.

PMID- 11321596
TI  - A case of Japanese cleidocranial dysplasia with a CBFA1 frameshift mutation.
AB  - Cleidocranial dysplasia (CCD), which is caused by mutations of the core binding
      factor alpha 1 (CBFA1)/runt-related gene 2 (Runx2), is an autosomal, dominantly
      inherited disorder of high penetrance affecting skeletal ossification and tooth
      development. Recently, we found a novel frameshift mutation 383-T-insertion
      (S128F) in exon 3 in the CBFA1 gene of a Japanese classic CCD patient. We
      describe our detailed investigation of the patient with CCD associated with the
      CBFA1 mutation. The patient showed the characteristic expression of CCD, such as
      dysplasia of the clavicles, patent fontanelles, short stature, impacted
      supernumerary teeth, and delayed eruption of the permanent teeth. In addition to
      these characteristics, orthopantomography delayed ossification of the mandibular
      symphysis and a three-dimensional computed tomograph (3D-CT) analysis showed
      hypoplasia of the zygomatic arch. Furthermore, the acellular cementum of an
      impacted supernumerary tooth was absent in this patient. Thus, the CBFA1 mutation
      was critical for the pathogenesis of CCD in this patient.

PMID- 11321597
TI  - Simultaneous induction of apoptosis, collagen type I expression and
      mineralization in the developing coronal suture following FGF4 and FGF2
      application.
AB  - This study aimed to evaluate the disturbances in normal coronal suture
      development resulting in craniosynostosis, a congenital disorder in which the
      calvarial sutures close prematurely. Craniosynostosis syndromes can be caused by
      mutations in the genes encoding for the fibroblast growth factor receptors
      (FGFRs) 1, 2, and 3. These gain-of-function mutations cause the transcribed
      receptor to be constitutively activated. To mimic this genetic defect, fibroblast
      growth factor (FGF) 2 or 4 was administered near the developing coronal suture in
      normal mouse embryos through ex utero surgery. The effect on apoptosis and bone
      differentiation, as collagen type I expression and mineralization, within the FGF
      exposed coronal suture was investigated through (immuno)histochemical staining.
      An increase in the number of apoptotic cells together with ectopic collagen type
      I expression within the suture and accelerated mineralization followed FGF
      application. Macroscopically, this presented as a synostotic coronal suture.
      These results suggest that both apoptosis and differentiation are two processes
      that are simultaneously implicated in synostosis of the coronal suture in case of
      a FGFR-related craniosynostosis.

PMID- 11321598
TI  - Cytokeratin, vimentin and E-cadherin immunodetection in the embryonic palate in
      two strains of mice with different susceptibility to glucocorticoid-induced
      clefting.
AB  - An immunohistochemical study analyzing the pattern of distribution of some
      intermediate filament proteins, keratin and vimentin and, one adhesion molecule,
      cadherin in different stages of developing secondary palate in two strains of
      mice with different H-2 backgrounds was undertaken to investigate differences
      between a strain that is susceptible to glucocorticoid-induced cleft palate
      (A/Sn) and one that is resistant to glucocorticoid-induced cleft palate (C57/BL).
      The heads of embryos were processed by standard immunohistochemistry with
      antipancytokeratin (KAE1), antikeratins 18 (K18) and 19 (K19), antivimentin, and
      anti E-cadherin antibodies. Immunostaining with KAE1 antibody showed differences
      between the strains. The reaction was stronger in the medial edge epithelia of
      palatal processes in the A/Sn strain at all stages of palatogenesis. The C57/BL
      strain showed a weak immunostain to KAE1. Antivimentin antibody stained the
      mesenchymal cells of palatal processes and K18 and K19 showed no reaction in
      either strain of mice. Anti E-cadherin antibody was detected in the medial
      palatal epithelium of both strains of mice and in all stages of palate
      development. No differences were observed in E-cadherin and vimentin immunostain
      in palatal epithelium between the strains. The different expression of some
      cytokeratins in the embryonic palatal epithelium suggests that these intermediate
      filament proteins may be involved in different susceptibility to glucocorticoid
      induced cleft palate in the mouse. The decreased immunoreaction of cytokeratins
      observed in the resistant strain would facilitate the disappearance of this
      molecule during the transformation from an epithelial to a mesenchymal phenotype
      that takes place during the development of the palate. These results may be
      related to the loss of cytokeratin expression observed during epithelial
      mesenchymal transformation in the embryonic palate.

PMID- 11321599
TI  - Collagen I and II mRNA distribution in the rat temporomandibular joint region
      during growth.
AB  - The distribution of type I and II collagen synthesis in the temporomandibular
      joint (TMJ) area of 1- to 28-day-old rats was studied after hybridization with
      probes to pro alpha1(I) and pro alpha1(II) collagen mRNA, and stain intensity
      through the various cartilaginous zones of the mandibular condyle and other areas
      of TMJ was assessed. The pro alpha(I) collagen mRNA was detected in the
      perichondrium/periosteum, in the fibrous and undifferentiated cell layers of the
      mandibular condyle, in the articular disc, and in all bone structures and
      muscles. The pro alpha1(II) collagen mRNA was found in the condylar cartilage and
      the articular fossa. Intensity in the condyle was highest in the chondroblastic
      layer and decreased towards the lower hypertrophic layer. In the condylar
      cartilage of the 21- to 28-day-old rats the chondroblastic cell zone was
      relatively narrow compared with the younger animals, whereas the reverse seems to
      be the case in the cartilage of the articular fossa. Changes in the pro
      alpha1(II) collagen mRNA were observed in the osseochondral junction area of the
      primary spongiosa, in that at the age of 5 days intense staining was found,
      whereas no staining was observed by 14 days. In the mineralizing zone, however,
      the majority of osteoblastic cells gave a positive signal with the pro alpha1(I)
      collagen probe. In conclusion, type II collagen synthesis of the mandibular
      condyle is restricted to its upper area. This differs from the long bone
      epiphyseal plate, where this type of collagen is produced virtually throughout
      the cartilage. Type II collagen synthesis of the fossal cartilage seems to
      increase as a function of age.

PMID- 11321600
TI  - Oculo-auriculo-vertebral (Goldenhar) spectrum associated with pericentric
      inversion 9: coincidental findings or etiologic factor?
AB  - Oculo-auriculo-vertebral (OAV) spectrum or Goldenhar syndrome is a complex and
      heterogeneous condition characterized by hemifacial microsomia (unilateral ear
      abnormalities and ipsilateral mandibular hypoplasia) as well as vertebral
      anomalies and epibulbar dermoids or lipodermoids. Although most cases of OAV
      spectrum are sporadic, both autosomal recessive and autosomal dominant
      inheritance have been reported. Furthermore, the association of OAV spectrum with
      different types of chromosomal abnormalities has been described. We present a
      premature newborn delivered after 36 weeks of gestation, whose birth weight was
      2,100 g, birth length 43 cm and head circumference 32.5 cm. OAV spectrum with
      associated axial skeleton anomalies, eventration of the right hemidiaphragm,
      accessory spleen, unlobulated right lung, agenesis of right kidney, right ovary
      and right uterine horn, and partial agenesis of corpus callosum were found. She
      was the second child of unrelated parents, who have a healthy boy. Both parents
      refused chromosomal analysis of their peripheral blood. Trypsin G-banding and C
      banding chromosomal analysis of the patient's peripheral blood revealed a
      pericentric inversion of chromosome 9 with break points at p11 and q13. This may
      be a coincidental or causal finding.

PMID- 11321601
TI  - Distinctive pitted enamel hypoplasia and short stature.
AB  - We report a case of postnatal onset short stature and a distinctive pitted enamel
      hypoplasia in a 19-year-old woman. Growth hormone deficiency and other endocrine
      deficiencies were excluded. Additional observations of similar cases might
      outline a newly recognized syndrome.

PMID- 11321602
TI  - Similarities in negative priming between persons with and those without mental
      retardation of equal chronological age.
AB  - Adolescents with and those without mental retardation participated in a negative
      priming procedure in two experiments. They identified letters to stimulus
      displays presented in pairs. Negative priming was observed as the slowing of
      response times when the distractor in the first display (prime) became the target
      in the second display (probe). In the standard procedure, all displays include
      one target and one distractor. In our modification, prime displays occasionally
      included a distractor without a target. Although adolescents with mental
      retardation typically do not exhibit negative priming when responding on the
      basis of stimulus identity, they did so with single letter primes in these
      experiments.

PMID- 11321603
TI  - Stereotypy and motor control: differences in the postural stability dynamics of
      persons with stereotyped and dyskinetic movement disorders.
AB  - We examined whether dynamic measures of postural stability differentiated persons
      with stereotyped movement disorder from persons with dyskinetic movement
      disorder. Participants from three groups (stereotypy, dyskinesia, control) were
      given a goal-oriented postural stability task, and performance was measured using
      a force platform and computerized posturographic techniques. The results showed
      that both movement disorder groups differed from the control group in the posture
      task. Further, the stereotypy and dyskinesia groups demonstrated markedly
      different postural movement profiles. The postural motion of the stereotypy group
      was characterized by greater amplitude and variability but lower complexity than
      the dyskinesia group. These results provide support for a motor control model of
      stereotypy.

PMID- 11321604
TI  - Effects of an aerobic rowing training regimen in young adults with Down syndrome.
AB  - Effects of a rowing exercise regimen on cardiovascular fitness of young adults
      with Down syndrome were examined. Sixteen young males with trisomy 21 (mean age
      21.3, mean IQ 38.8) were randomly assigned to either a control or exercise group.
      All participants performed pre- and posttraining graded exercise tests on a
      treadmill and rowing ergometer. The exercise group performed a 16-week rowing
      ergometry training regimen. Following training, no changes in cardiovascular
      fitness had occurred for this group. However, they reached significantly higher
      levels of work performance for both treadmill and rowing ergometer posttraining
      tests. Results show that an exercise training regimen did not improve the
      cardiovascular fitness of young adults with Down syndrome but did improve
      exercise endurance and work capacity.

PMID- 11321605
TI  - Assessment of visual acuity in relation to central nervous system activation in
      children with mental retardation.
AB  - Assessment of visual acuity was combined with observations of behavioral state
      indicating CNS activation in 24 individuals with mental retardation. Visual
      acuity was assessed by presentations of Teller Acuity Cards on two occasions.
      Behavioral state was classified along a scale with four categories during visual
      acuity testing. Results showed good test-retest reliability for the Teller Acuity
      Cards. Six participants had different behavioral state scores on the two test
      occasions, but displayed similar visual acuity on both tests. No participant
      rated as "drowsy" displayed responses on the acuity test. Results indicate that
      forced-choice preferential-looking technique can be used to test visual acuity in
      this population unless the participant is drowsy.

PMID- 11321606
TI  - Role of planning, attention, and simultaneous and successive cognitive processing
      in facial recognition in adults with mental retardation.
AB  - Fifty adults with mental retardation completed the Cognitive Assessment System
      and the Facial Discrimination Task. Performances on the Facial Discrimination
      Task Emotion and Age Tasks were significantly correlated to the Cognitive
      Assessment System total score. Hierarchical regression analyses showed that
      processing of emotional stimuli was related to simultaneous and successive
      processing; whereas attention and planning failed to add significantly. The
      Emotion and Age Tasks yielded similar results, suggesting that cognitive
      processes are involved in processing facial stimuli in a similar way regardless
      of the type of facial cues involved. The results are discussed vis-a-vis modular
      models of emotion, future research directions, and the Age Task as a control
      task.

PMID- 11321607
TI  - Discriminant validity of the Vineland Scales: score profiles of individuals with
      mental retardation and a specific disorder.
AB  - Utility of the Vineland Adaptive Behavior Scales-Expanded Form to discriminate
      among areas of adaptive behavior was substantiated by comparing profiles of
      scores obtained by three groups of individuals with mental retardation and either
      a communication, social behavior, or motor abilities disorder with those of
      matched individuals with mental retardation but no other disorder. Individuals
      with social behavior disorders obtained lower scores only in the Socialization
      domain; those with motor disorders, in the Motor domain and in the Personal and
      Domestic subscales that require motor competencies; and those with communication
      disorders, lower scores in the Communication domain and in the Community and
      Interpersonal Relationships subscales requiring expressive competencies. The
      utility of the Vineland Scales in obtaining an ecological evaluation of
      individuals with mental retardation is discussed.

PMID- 11321608
TI  - Transition to adulthood: mental retardation, families, and culture.
AB  - A conceptual model was proposed guiding a study of mental retardation and family
      well-being during the transition from late adolescence into young adulthood. The
      developmental period from about age 18 to 26 is critical, in that formal
      schooling ends and changes in residential, vocational, and social status are
      likely. Furthermore, the proposal was made that the success of transitional
      experiences in these three realms will influence family well-being, an outcome of
      primary interest at this stage of the lifecycle of the family. Individual
      characteristics, environment and culture, and family involvement with programs
      are hypothesized to influence family well-being, but primarily through their
      impact on transition success.

PMID- 11321609
TI  - Early development of self-injurious behavior: an empirical study.
AB  - The early development of SIB in young children with developmental disabilities
      was examined by tracking over an 18-month period 16 school-age children who had
      recently started to show early SIB. Naturalistic observations were conducted in
      each child's classroom every 3 months, and the association between early SIB and
      environmental events was examined. Results showed that for the 4 children whose
      early SIB had escalated over this period, there was a significant association
      between early SIB and low levels of social contact across observation points,
      supporting models of the development of SIB. This association might be considered
      as a risk marker for the exacerbation of SIB. Implications of this finding for
      targeting early interventions for SIB are discussed.

PMID- 11321610
TI  - The perception of speech sounds by the human brain as reflected by the mismatch
      negativity (MMN) and its magnetic equivalent (MMNm).
AB  - The present article outlines the contribution of the mismatch negativity (MMN),
      and its magnetic equivalent MMNm, to our understanding of the perception of
      speech sounds in the human brain. MMN data indicate that each sound, both speech
      and nonspeech, develops its neural representation corresponding to the percept of
      this sound in the neurophysiological substrate of auditory sensory memory. The
      accuracy of this representation, determining the accuracy of the discrimination
      between different sounds, can be probed with MMN separately for any auditory
      feature (e.g., frequency or duration) or stimulus type such as phonemes.
      Furthermore, MMN data show that the perception of phonemes, and probably also of
      larger linguistic units (syllables and words), is based on language-specific
      phonetic traces developed in the posterior part of the left-hemisphere auditory
      cortex. These traces serve as recognition models for the corresponding speech
      sounds in listening to speech. MMN studies further suggest that these language
      specific traces for the mother tongue develop during the first few months of
      life. Moreover, MMN can also index the development of such traces for a foreign
      language learned later in life. MMN data have also revealed the existence of such
      neuronal populations in the human brain that can encode acoustic invariances
      specific to each speech sound, which could explain correct speech perception
      irrespective of the acoustic variation between the different speakers and word
      context.

PMID- 11321611
TI  - Assessing supraspinal modulation of pain perception in individuals at risk for
      hypertension.
AB  - In this study we tested the hypothesis that hypoalgesia in individuals at risk
      for hypertension is related to enhanced activation of supraspinal pain modulation
      systems. Supraspinal inhibition of pain signals was assessed using a diffuse
      noxious inhibitory control paradigm, in which a noxious conditioning stimulus was
      used to suppress pain in response to a noxious test stimulus applied to a remote
      area of the body. Specifically, the nociceptive flexion reflex (NFR) was assessed
      in 113 healthy young adults before, during, and after exposure to forearm
      tourniquet ischemia. Consistent with previous evidence of hypoalgesia in
      individuals at risk for hypertension, offspring of hypertensive individuals
      exhibited significantly higher NFR thresholds than offspring of normotensive
      persons. Although NFR activity was significantly decreased in all participants
      during concomitant application of forearm ischemia, the degree of attenuation of
      NFR activity was not significantly different as a function of risk for
      hypertension.

PMID- 11321612
TI  - An early electrophysiological sign of semantic processing in basal extrastriate
      areas.
AB  - Recognition potential (RP), a recently discovered electrophysiological response
      of the brain, is sensitive to semantic aspects of stimuli. Given its peak values
      (about 250 ms), RP may be a good candidate for the study of semantic processing
      during its occurrence. However, its topography and neural generators are largely
      unknown. To improve this state of affairs, high-resolution electroencephalography
      and brain electrical source analysis were carried out. Results suggest a possible
      origin of RP in the lingual gyrus, hence reflecting the activity of the basal
      extrastriate areas. RP therefore appears to be a highly valuable tool in the
      study of those regions considered to be the "third language areas" (in addition
      to Broca's and Wernicke's areas), whose precise role in language processing is
      still largely unknown. Another important finding was that RP amplitude in the
      left hemisphere differed as a function of the semantic category of the stimuli,
      providing evidence for the sensitivity of this component to semantic
      categorization. A tentative proposal is made with regard to the role of the basal
      extrastriate areas.

PMID- 11321613
TI  - Saccadic hypometria in drug-naive and drug-treated schizophrenic patients: a
      working memory deficit?
AB  - In certain conditions patients with schizophrenia make markedly smaller
      (hypometric) saccades than controls. This hypometria has been thought to reflect
      dopaminergic blockade as a result of antipsychotic medication. We tested this
      hypothesis by comparing the performance of an antipsychotic-naive group and an
      antipsychotic-treated group of first-episode schizophrenic patients on a
      predictive saccade paradigm. We explored the possibility that hypometria reflects
      a spatial working memory deficit by correlating performance on neuropsychological
      tests of mnemonic function with saccadic accuracy. Both the drug-naive and
      treated schizophrenic patients made hypometric saccades when compared with a
      group of matched controls. Primary saccade amplitude also correlated
      significantly with performance on some of the neuropsychological tests. These
      results are discussed in terms of the roles of cortical dopamine and working
      memory deficits in schizophrenic patients.

PMID- 11321614
TI  - Neural sources involved in auditory target detection and novelty processing: an
      event-related fMRI study.
AB  - We used event-related functional magnetic resonance imaging (erfMRI) techniques
      to examine the cerebral sites involved with target detection and novelty
      processing of auditory stimuli. Consistent with the results from a recent erfMRI
      study in the visual modality, target processing was associated with activation
      bilaterally in the anterior superior temporal gyrus, inferior and middle frontal
      gyrus, inferior and superior parietal lobules, anterior and posterior cingulate,
      thalamus, caudate, and the amygdala/hippocampal complex. Analyses of the novel
      stimuli revealed activation bilaterally in the inferior frontal gyrus, insula,
      inferior parietal lobule, and in the inferior, middle, and superior temporal
      gyri. These data suggest that the scalp recorded event-related potentials (e.g.,
      N2 and P3) elicited during similar tasks reflect an ensemble of neural generators
      located in spatially remote cortical areas.

PMID- 11321615
TI  - P300 and alpha event-related desynchronization (ERD).
AB  - In the present study we evaluated the relationships between the P300 event
      related potential and event-related desynchronization (ERD) of
      electroencephalographic alpha activity by simultaneously analyzing P300 as well
      as 7-10- and 10-14-Hz alpha ERD responses from auditory passive and active
      oddball conditions. We compared the effects of task (target vs. nontarget) and
      electrode (Fz, Cz, Pz) on P300 and ERD, and correlated P300 amplitude/latency
      with ERD maximal amplitude/latency across individuals. The major findings were
      that P300 as well as slow and fast alpha ERD manifested similar task and
      electrode effects. P300 preceded ERD and predicted individual variance of both
      slow and fast alpha ERD. The relationships of P300 with alpha ERD were different
      for the slow and fast alpha frequencies. These findings indicate that P300 and
      ERD are related such that slow and fast alpha ERDs are specifically guided or
      modified by the internal event(s) indexed by P300.

PMID- 11321616
TI  - Ocular motor delayed-response task performance among patients with schizophrenia
      and their biological relatives.
AB  - Schizophrenia patients and their relatives have saccadic abnormalities
      characterized by problems inhibiting a response. The dorsolateral prefrontal
      cortex and its associated circuitry ostensibly mediate inhibition and support
      correct delayed response performance. In this context, two components of delayed
      response task performance are of interest: memory saccade metrics and error
      saccades made during the delay. To evaluate these variables, an ocular motor
      delayed response task was presented to 23 schizophrenia patients, 25 of their
      first-degree biological relatives, and 19 normal subjects. The measure that best
      differentiated groups was an increased frequency of error saccades generated
      during the delay by schizophrenia subjects and relatives. Decreased memory
      saccade gain also characterized patients and relatives. The similar pattern of
      results demonstrated by the patients with schizophrenia and their relatives
      suggests that performance on ocular motor delayed response tasks, either alone or
      in combination with other saccadic variables, may provide useful information
      about neural substrates associated with a liability for developing schizophrenia.

PMID- 11321617
TI  - An electromyographic investigation of the effect of stimulus-response mapping on
      choice reaction time.
AB  - The activity of the agonist muscles was recorded during the performance of a two
      choice visual reaction time (RT) task in which the compatibility of the stimulus
      response mapping was manipulated. Correct trials were distinguished according to
      whether or not the activation of the agonist of the required response was
      preceded by an activation of the agonist of the nonrequired response. Double
      activation trials were more numerous for the incompatible than for the compatible
      mapping. Furthermore, these trials yielded longer RTs than the single muscular
      activation trials. These results suggest that initial activations of nonrequired
      responses are more frequently aborted and corrected when the mapping is
      incompatible than when it is compatible. This finding supports the dimensional
      overlap model of stimulus-response compatibility (S. Kornblum, T. Hasbroucq, & A.
      Osman, 1990).

PMID- 11321618
TI  - Optimal signal bandwidth for the recording of surface EMG activity of facial,
      jaw, oral, and neck muscles.
AB  - Spontaneous pericranial electromyographic (EMG) activity is generally small and
      is contaminated by strong low-frequency artifacts. High-pass filtering should
      suppress artifacts but affect EMG signal power only minimally. In 24 subjects who
      performed a warned simple reaction time task, the optimal high-pass cut-off
      frequency was examined for nine different pericranial muscles. From four
      experimental conditions (visual and auditory reaction signals combined with hand
      and foot responses), 1-min EMG recordings were selected (bandwidth: 0.4-512 Hz)
      and divided into 60 1-s data segments. These segments were high-pass filtered,
      the -3-dB cut-off frequency varying from 5 to 90 Hz, and subjected to power
      spectral analysis. Optimal high-pass filter frequencies were determined for the
      mean power spectra based on visual estimation or comparison with a theoretical
      spectrum of the artifact-free EMG signal. The optimal frequencies for the
      different muscles varied between 15 and 25 Hz and were not influenced by stimulus
      or response modality. For all muscles, a low-pass filter frequency between 400
      and 500 Hz was appropriate.

PMID- 11321619
TI  - Influence of focused auditory attention on cochlear activity in humans.
AB  - The mammalian auditory system contains descending pathways that originate in the
      cortex and relay at various intermediate levels before reaching the peripheral
      sensory organ of Corti. The last link in this chain consists of the olivocochlear
      bundle. The activity of this bundle can be measured through otoacoustic
      emissions, which are acoustic signatures of the cochlear biomechanical activity.
      In the present study, it was hypothesized that frequency-specific activation of
      the olivocochlear bundle in the contralateral ear would show up as frequency
      specific variations in otoacoustic emission amplitude in the ipsilateral ear. Two
      groups of young adult subjects participated in this experiment. Evoked
      otoacoustic emissions were recorded in the ipsilateral ear at two test
      frequencies (1 and 2 kHz). Subjects had to detect probe tones at a given
      frequency in background noise in the contralateral ear. Larger efferent
      activation was measured at test frequencies on which attention is focused. This
      result provides evidence for an influence of attention on the auditory periphery
      via descending projections.

PMID- 11321620
TI  - Working memory constraints on syntactic processing: an electrophysiological
      investigation.
AB  - Event-related potentials (ERPs) and reaction times (RTs) were used to study how
      the processing of sentences with morphosyntactic violations is constrained by
      working memory (WM) capacity. The available WM capacity was varied by three
      orthogonal manipulations: (1) syntactic complexity; (2) additional WM load; and
      (3) verbal WM span. The processing of the morphosyntactic violations was
      reflected in longer RTs in ungrammatical compared with grammatical sentences, and
      in an anterior negativity and a centroparietal positivity in the ERPs. While the
      behavioral grammaticality effect was not influenced by the WM manipulations, the
      ERP effects were. The amplitude of the anterior negativity was modulated by the
      combination of complexity and load, and by WM span. The onset of the
      centroparietal positivity was delayed in the high-load condition, and for the low
      span group. ERPs over the course of the sentences showed a frontal negative slow
      wave under high WM load, largest for the low-span group. The finding that online
      syntactic processing is related to WM span and to additional WM load does not
      support the theory that there is a WM capacity specific for syntactic processing.

PMID- 11321621
TI  - Saccade initiation and accuracy in gaze shifts are affected by visual stimulus
      significance.
AB  - The effect of visual stimulus significance on saccade latency and accuracy in
      gaze shifts was investigated. Stimulus significance refers to the temporal
      proximity of an imperative stimulus. It was hypothesized that stimulus
      significance serves as a cue that influences the observer's expectancy for a
      forthcoming event. Twenty-one undergraduate students participated in two
      experiments involving monitoring of visual events. Stimuli were a sequence of
      1,000 single-digit integers presented one at a time at 9 degrees of visual angle
      to the left or right of a fixation point in random order. The subject was
      required to make a manual response after the presentation of a sequence of two
      odd integers. The probability of the subsequent integer being odd, a "target,"
      after the presentation of an odd integer was 0.75. The integer after a target was
      always an even integer. When stimulus location was unpredictable (Experiment 1),
      latency of visually guided saccades to the target was shorter (p < .01) than to
      the nontarget stimuli. Under the condition of predictable stimulus location
      (Experiment 2), anticipatory saccades to the target occurred earlier (p < .01),
      more frequently (p < .01), and more accurately (p < .05). Our results suggest
      that both timing and accuracy of gaze shift are affected by the observer's
      expectation of future events.

PMID- 11321622
TI  - Pupillary responses and processing resources on the visual backward masking task.
AB  - Task-evoked pupillary responses were recorded during a visual backward masking
      task as an index of resource allocation. Increased pupillary dilation indicates
      increased allocation of processing resources to the task. Consistent with
      numerous studies, detection accuracy increased with longer interstimulus
      intervals and approximated no-mask accuracy in the 300-ms condition. Pupillary
      dilation responses were significantly greater during task performance (cognitive
      load) than during a passive stimulus viewing condition (no-load) and were
      significantly greater in the 300-ms condition than the no-mask condition.
      Consistent with models of early visual information processing, the results
      suggest that the mask demanded extra processing resources when it followed the
      target by more than 100 ms. Pupillography methods may be useful in evaluating the
      contribution and timing of resource-demanding processes during early visual
      information processing.

PMID- 11321623
TI  - Independent manipulation of stimulus change and unexpectedness dissociates
      indices of the orienting response.
AB  - Results obtained with the standard repetition-change paradigm of orienting
      research cannot be attributed unambiguously to either stimulus change or to
      unexpectedness. By adding announcement conditions, in which participants were
      told about an impending stimulus change, these two factors were disentangled. In
      Experiment 1, reaction times (RTs) were longer and ratings of surprise were
      higher with unannounced than with announced stimulus change. In contrast, larger
      skin conductance response (SCR) magnitudes occurred following change,
      irrespective of its congruence with participants' expectations. Experiment 2
      replicated the results for SCR magnitude and, furthermore, revealed the same
      pattern of results for the evoked cardiac response. Surprise ratings again
      reflected the unexpectedness of stimulus presentations. The dissociation between
      RT and autonomic measures provides difficulties for resource allocation accounts
      of the orienting response.

PMID- 11321624
TI  - Preattentive processing of spectral, temporal, and structural characteristics of
      acoustic regularities: a mismatch negativity study.
AB  - In the present study we investigated the relationship between detecting
      violations of structural regularities of tone sequences and detecting deviations
      from temporal regularities or repetitive spectral auditory stimulus features.
      Twelve subjects were presented with randomized sequences of two tones (differing
      both in frequency and intensity) delivered alternately to the left and right ears
      at a constant stimulus onset asynchrony (SOA). In separate blocks, occasional
      deviant stimuli broke one, two, or three of the following regularities: spatial
      alternation, the constancy of SOA, or the dominant frequency-intensity
      conjunctions. Unlike the mismatch negativity (MMN) elicited by alternation-plus
      SOA deviants, the MMN elicited by alternation-plus-conjunction deviants was
      approximately equal to the sum of the two corresponding single-deviant MMNs.
      These results suggest that the preattentive change-detection system processes
      infrequent violations of the structural regularities of sound sequences together
      with changes in temporal regularities, but separately from changes in repetitive
      spectral sound features. The MMN elicited by the triple-deviant stimuli
      corroborated these conclusions.

PMID- 11321625
TI  - Regional brain activation as a biological marker of affective responsivity to
      acute exercise: influence of fitness.
AB  - Previous research has shown that regional brain activation, assessed via frontal
      electroencephalographic (EEG) asymmetry, predicts affective responsivity to
      aerobic exercise. To replicate and extend this work, in the present study we
      examined whether resting brain activation was associated with affective responses
      to an acute bout of aerobic exercise and the extent to which aerobic fitness
      mediated this relationship. Participants (high-fit, n = 22; low/moderate-fit, n =
      45) ran on a treadmill for 30 min at 75% VO2max. EEG and affect were assessed pre
      and 0-, 10-, 20-, and 30-min postexercise. Resting EEG asymmetry predicted
      positive affect (as measured by the energetic arousal subscale of the Activation
      Deactivation Adjective Check List) postexercise. Furthermore, resting frontal EEG
      asymmetry predicted affect only in the high-fit group, suggesting the effect
      might be mediated by some factor related to fitness. It was also shown that
      subjects with relatively greater left frontal activation had significantly more
      energy (i.e., activated pleasant affect) following exercise than subjects with
      relatively greater right frontal activation. In conclusion, aerobic fitness
      influenced the relationship between resting frontal asymmetry and exercise
      related affective responsivity.

PMID- 11321626
TI  - Social-cognitive processes in preschool boys with and without oppositional
      defiant disorder.
AB  - The social-cognitive characteristics of 88 preschool boys with Oppositional
      Defiant Disorder (ODD) and 80 nondisruptive boys were assessed 3 times over a 2
      year period. Three questions were addressed: (1) Do social-cognitive processes
      (encoding, attribution, problem solving, and response evaluation) distinguish
      clinic-referred preschool boys from peers without behavior problems? (2) What is
      the relation between preschoolers' social-cognitive processes and observed
      problem behavior? (3) Are the social-cognitive processes of clinic boys with ODD
      influenced by comorbidity with Attention Deficit Hyperactivity Disorder (ADHD)?
      Boys were presented hypothetical, peer-oriented social dilemmas to resolve. At
      all 3 assessments, clinic boys were twice as likely as were comparison group boys
      to generate aggressive solutions. Relative to comparison boys, clinic boys'
      encoding of social information was less accurate. The groups did not differ in
      their attributions or response evaluations. Verbal IQ and language skills were
      modestly correlated with problem solving and encoding. Within the clinic group,
      social-cognitive processes were not affected by ADHD comorbidity and they showed
      little relation to later diagnostic status or severity of behavior problems.

PMID- 11321627
TI  - Ritualistic behavior in young children.
AB  - The aim of this study was to examine ritualistic behavior at its developmental
      peak. Children 20-59 months of age were sampled through a national system of
      daycare centers in Israel (N = 228). The order of onset of the ritual behaviors
      measured was virtually identical to that reported for an American sample (D. W.
      Evans et al., 1997). Gender and age effects were found for fearfulness but not
      for ritualistic behavior. Maternal reports of ritualistic behavior were highly
      correlated with reported fears, and with shy and emotional temperament. Mothers
      of the children who were in the top 10% in their use of rituals according to
      maternal report, worried about their child's ritualistic behavior, even though
      maternal worry was not correlated with ritualistic behavior for the whole
      distribution.

PMID- 11321628
TI  - Measuring qualitative aspects of preschool boys' noncompliance: the Response
      Style Questionnaire (RSQ).
AB  - Child noncompliance is a core maladjustment factor in current clinical models of
      aggression and antisocial development. However, little is known about the
      relations among qualitative aspects of child noncompliance and aggressive
      maladjustment. The authors developed the Response Style Questionnaire, an
      instrument designed to measure the multidimensional qualities of child
      noncompliance, and tested its validity and reliability. Tests of internal
      validity provided a five-factor solution, featuring distinctions in noncompliance
      quality between and among skilled noncompliance (verbally skilled and emotionally
      regulated) and unskilled noncompliance (overt/confrontational, covert/sneaky, and
      emotionally labile). Theory-driven tests of external validity using peer
      adjustment variables as criteria provided discriminant prediction (a) among
      qualitatively distinct aspects of noncompliance and (b) between noncompliance
      qualities and rate. Discussion focuses on a modified view of the nature and role
      of noncompliance in aggressive and antisocial development.

PMID- 11321629
TI  - A multivariate analysis of the revised Conners' Teacher Rating Scale with low
      income, urban preschool children.
AB  - The present investigation addressed the utility of the revised Conners' Teachers
      Rating Scale (CTRS-28) with low-income urban preschool children. CTRS-28 ratings
      for a large sample of preschool children from an urban Head Start program were
      analyzed using exploratory factor analysis. Analyses yielded a 3-factor
      structure: Conduct problems, Hyperactivity, and Passivity. Further analyses cross
      validated this structure for males and females and supported its integrity.
      Multimethod, multisource validity analyses substantiated the CTRS-28 dimensions.
      The Play Disruption factor of the parent and teacher Penn Interactive Peer Play
      Scales (PIPPS) provided convergent validity for the Conduct and Hyperactivity
      factors of the CTRS-28, whereas the Play Interaction factor revealed divergent
      validity. The Play Disconnection factor of the PIPPS validated the CTRS-28
      Passivity factor. The Q-Sort Emotional Regulation scale provided divergent
      validity for the Conduct and Hyperactivity factors and likewise the Q-Sort
      Autonomy scale provided divergent validity for the Passivity factor. Age and sex
      differences were assessed across the 3 factors of the derived preschool
      structure. A main effect was found for sex and age indicating that boys displayed
      higher levels of Hyperactivity and Passivity problems than girls did. Similarly,
      4-year-old children demonstrated higher levels of Passivity problems than did 5
      year-old children.

PMID- 11321630
TI  - Relationship between specific adverse life events and psychiatric disorders.
AB  - This study examines whether certain psychiatric disorders are associated more
      closely with adverse life events than other disorders are, and whether some
      adverse life events are associated with a specific group of disorders (e.g.,
      depressive disorders), but not with other disorders (e.g., anxiety disorders). A
      probability sample of youth aged 9-17 at 4 sites is used (N = 1,285). Univariate
      and multivariate logistic regressions identify specific relationships between 25
      adverse life events and 9 common child and adolescent psychiatric disorders,
      measured by the Diagnostic Interview Schedule for Children. Conduct Disorder,
      Oppositional Defiant Disorder, Major Depressive Disorder, and Dysthymia are
      significantly associated with many of the adverse life events examined, whereas
      Attention Deficit/Hyperactivity Disorder, Agoraphobia, and Social Phobia are
      related to very few. This study suggests that certain psychiatric disorders may
      be more closely associated with adverse life events than other psychiatric
      disorders are, and that some adverse life events seem to be related to specific
      types of disorders.

PMID- 11321631
TI  - Ukrainian application of the Children's Somatization Inventory: psychometric
      properties and associations with internalizing symptoms.
AB  - This paper examines the psychometric properties of the Children's Somatization
      Inventory (CSI) in 600 10-12-year old children in Kyiv, Ukraine, replicating and
      extending the original findings from a sample in Nashville, Tennessee (J. Garber
      et al. 1991). The Kyiv children had significantly lower CSI total scores and
      reported significantly fewer symptoms than the American children. The Kyiv
      mothers, however, reported significantly more somatization symptoms in their
      children than did the American mothers. A factor analysis of the children's data
      yielded four similar factors encompassing pseudoneurologic, cardiovascular,
      gastrointestinal, and pain/weakness symptoms. Consistent with the findings from
      the Nashville study, the CSI was significantly related to the children's self
      reports of health and depressive and anxiety symptoms and to maternal reports of
      child depression and anxiety symptoms. In addition, although more children with
      the highest CSI scores (25+) reported various illness experiences than those with
      0-1 symptoms, no differences were found in the school absentee records. Thus, the
      results were congruent with the findings of the Nashville study, indicating that
      the CSI reliably measured somatization in this Ukrainian sample.

PMID- 11321632
TI  - Parental alcoholism and co-occurring antisocial behavior: prospective
      relationships to externalizing behavior problems in their young sons.
AB  - The hypothesis that parental alcoholism and co-occurring antisocial behavior
      would be indirectly linked to child externalizing behavior problems through child
      lack of control, current levels of parent depression, family conflict, and parent
      child conflict was tested using manifest variable regression analysis.
      Participants were a community sample of 125 families with an alcoholic father and
      83 ecologically matched but nonsubstance abusing families involved in the first 2
      waves of an ongoing longitudinal study (with 3 years between each wave). All
      families had a biological son who was 3-5 years old at study onset. Results
      revealed that child lack of control mediated the relation between paternal
      alcoholism and the son's subsequent externalizing behavior problems. Family
      conflict was a significant mediator of maternal and paternal lifetime antisocial
      behavior effects and father-son conflict mediated paternal lifetime antisocial
      behavior effects. Study implications are discussed within the context of parental
      socialization of antisocial behavior.

PMID- 11321633
TI  - Perceived structure from optic flow: consistent versus variable mapping of 3-D
      Euclidean structure.
AB  - In an earlier study (Borjesson & Lind, 1996), the perception of Euclidean
      structure from polar projected two-frame apparent motion sequences was studied.
      The results showed that Euclidean structure is not perceived. However, at larger
      visual angles a certain consistency in the mapping between distal and perceived
      structure exists. The aim of the present study was to more precisely examine how
      this degree of consistency varies as a function of visual angle. In Experiments 1
      and 2, slant judgments of simulated and real planes indicated that the degree of
      consistency is a positive function of visual angle. No definite sign of a
      Euclidean mapping could, however, be found even in the full view condition.
      Experiment 3 examined texture gradients and the response method used. The results
      showed that texture gradients did not influence the degree of consistency of the
      mapping between distal and judged depth and that the response method was both
      reliable and valid. However, texture gradients did influence the absolute values
      of the slant judgments. The role of Euclidean and affine mappings of distal
      structure is discussed and it is proposed that the perceptually important
      distinction is not between affine and Euclidean mapping, but rather between two
      types of affine mappings--consistent and variable.

PMID- 11321634
TI  - Do traumatic events influence cognitive schemata?
AB  - Within the field of crisis psychology empirical research on the subject whether
      cognitive schemata are influenced by victimization, and whether possible changes
      in cognitive schemata are related to post-traumatic stress disorder (PTSD) is
      somewhat sparse. In the present study cognitive processing of 602 parents, who
      had lost an infant, were examined. Among other things results showed a
      significant relationship between level of cognitive processing and symptoms of
      PTSD. When items selected to reflect fundamental assumptions about the self and
      the world were assessed, there were only few differences between parents who had
      lost an infant, and the control group. Furthermore, there were numerous
      significant relations between items selected to reflect fundamental assumptions
      and symptoms of PTSD. The results are discussed in relation to central theories
      within the cognitive area of crisis psychology and recommendations for future
      research are offered.

PMID- 11321635
TI  - A dynamical systems interpretation of a dimensional model of emotion.
AB  - The dimensional structure of emotion was investigated using self reports of
      induced mood and idiographic and nomothetic analyses. Subjects attended four
      experimental sessions during which an array of affective states was induced via
      auditory, visual, and imaginal channels. For each of 118 stimulus events,
      subjects self-rated their response. Factor analysis yielded the predicted bipolar
      factors of valence and arousal: these were obtained in group-aggregated analysis
      and subsequently confirmed as change dimensions at the intraindividual level.
      Controversy over the fundamental dimensions of affective space was considered
      with respect to methodological issues such as factor rotation and sampling of
      data space. Valence and arousal are discussed as motivational, driving parameters
      of affective experience and a dynamical systems conceptualization of emotion is
      proposed.

PMID- 11321636
TI  - DMT interminable--a re-reply to I. Zuber and B. Ekehammar.

PMID- 11321637
TI  - Novice construction of chess memory.
AB  - Novice acquisition of skilled recall of chess positions was studied in an
      experiment in which two novices studied a series of five hundred chess positions
      during a period of several months. They spent fifteen minutes to half an hour a
      day teaching themselves these positions. As a result their skill in recalling
      chess positions rose from sixteen percent to somewhere between forty to fifty
      percent. The learning curve proved to have a shape which indicates that in the
      beginning learning is very fast but after some 100-150 studied positions the
      speed of learning decreases substantially. A computer simulation was used to
      model the results and analyse alternative explanations. Two alternative ways of
      thinking were tested. In the first, chunk construction was assumed to be based on
      the neighbourhood of associated pieces. The second model assumed a frequency
      based correlative association process. Although the learning curves of the two
      models are very similar in shape to those of the subjects, the frequency-based
      associative model gave a better explanation for the data. This is why it is
      natural to suggest that common co-occurrence in addition to easily recognizable
      chess-specific characteristics, like colour and type of pieces, guide associative
      processes during chess players' learning of chess-specific chunks.

PMID- 11321638
TI  - What do computer models of cognition explain: a reply to Gobet.
AB  - The differences between Gobet's views and ours call attention to some points
      concerning the argumentative status of computational models. If we have two
      fundamentally different models which reasonably accurately simulate a phenomenon,
      we must ask, what is the argumentative status of the models in psychological
      terms. Moreover, if it is possible to present different models of same phenomena,
      what is the general argumentative power of models in psychology? As the kind of
      differences between our views and the ones of Gobet's are common in modelling, we
      briefly call attention to these foundational issues in our paper.

PMID- 11321639
TI  - The short-EMBU in East-Germany and Sweden: a cross-national factorial validity
      extension.
AB  - The factorial stability and reliability of the 23-item s(hort)-EMBU previously
      demonstrated to be satisfactory in samples of students from Greece, Guatemala,
      Hungary and Italy, were extended with 791 students from East-Germany and Sweden.
      Previous findings on factorial validity, internal reliability and correlations
      among scales were replicated. The 23-item form thus continues to be recommended
      as a reliable functional equivalent to the early 81-item EMBU, when the clinical
      and/or research context does not adequately permit application of time-consuming
      test batteries.

PMID- 11321640
TI  - Errors in subtractions: judged and observed frequencies.
AB  - In a first study 10 adults, aged 24-44 years, solved all 105 subtraction problems
      in the form M - N = , where 0 < or = M < or = 13, 0 < or = N < or = 13 and N < or
      = M. Each participant solved every problem 10 times and in total there were 10
      500 answers. Answers, response latencies and errors were registered.
      Retrospective verbal reports were also given, indicating how a solution was
      reached: (1) via a (conscious) reconstructive cognitive process or (2) via an
      (unconscious) reproductive (retrieval) process. The participants made 291 errors
      (2.8%) when solving the subtractions in study 1. The rate of self-correction was
      very high, 92%. In a second study 27 undergraduate students estimated overall
      error rates, including self-corrected errors for the 105 subtraction problems
      used in the first study. Judged and actual error rates were compared. The
      participants systematically underestimated error rates for error prone problems
      and overestimated error rates for error free problems. The participants were
      fairly accurate when they predicted problems that were most error prone, with a
      hit rate of 0.67 for the (18) problems predicted as the most error prone ones. In
      contrast, predictions of which problems were error free were very poor with a hit
      rate of only 0.20 of the problems predicted as error free really having no errors
      in study 1. The correlation between judged error rates and frequencies for
      actually made errors was 0.69 for answers belonging to reconstructive solutions.
      In contrast, there was no significant correlation between judged and actual error
      rates at all for retrieved solutions, possibly reflecting the inaccessibility to
      consciousness of quick retrieval processes.

PMID- 11321641
TI  - Asymmetries in the processing of emotionally valenced words.
AB  - Earlier research has shown a valence dependent encoding asymmetry of emotional
      words (e.g., Pratto & John, 1991; White, 1996; Stenberg, Wiking & Dahl, 1998). To
      further study this asymmetry, two word detection experiments were performed based
      on the following hypothesis: when there is a more thoroughly processing of the
      valence, in this case a valence categorisation, there will be, in a subsequent
      task, prolonged latencies for negative words, compared to positive words. The
      result gave significantly prolonged response latencies for negative words
      compared to positive ones in the subsequent detection task when using an
      affective orienting task, something not found using a non-affective orienting
      task. The results support the Mobilization-Minimization hypothesis (Taylor,
      1991), according to which negative events and stimuli occupy more cognitive
      resources, but with some limitation: the affective asymmetry, with prolonged
      latencies for negative words, occurs only when there is a deepened encoding of
      the affective component of the words.

PMID- 11321642
TI  - Hemodynamic parameters and early intimal thickening in branching blood vessels.
AB  - Intimal thickening due to atherosclerotic lesions or intimal hyperplasia in
      medium to large blood vessels is a major contributor to heart disease, the
      leading cause of death in the Western World. Balloon angioplasty with stenting,
      bypass surgery, and endarterectomy (with or without patch reconstruction) are
      some of the techniques currently applied to occluded blood vessels. On the basis
      of the preponderance of clinical evidence that disturbed flow patterns play a key
      role in the onset and progression of atherosclerosis and intimal hyperplasia, it
      is of interest to analyze suitable hemodynamic wall parameters that indicate
      susceptible sites of intimal thickening and/or favorable conditions for thrombi
      formation. These parameters, based on the wall shear stress, wall pressure, or
      particle deposition, are applied to interpret experimental/clinical observations
      of intimal thickening. Utilizing the parameters as "indicator" functions,
      internal branching blood vessel geometries are analyzed and possibly altered for
      different purposes: early detection of possibly highly stenosed vessel segments,
      prediction of future disease progression, and vessel redesign to potentially
      improve long-term patency rates. At the present time, the focus is on the
      identification of susceptible sites in branching blood vessels and their
      subsequent redesign, employing hemodynamic wall parameters. Specifically, the
      time-averaged wall shear stress (WSS), its spatial gradient (WSSG), the
      oscillatory shear index (OSI), and the wall shear stress angle gradient (WSSAG)
      are compared with experimental data for an aortoceliac junction. Then, the OSI,
      wall particle density (WPD), and WSSAG are segmentally averaged for different
      carotid artery bifurcations and compared with clinical data of intimal
      thickening. The third branching blood vessel under consideration is the graft-to
      vein anastomosis of a vascular access graft. Suggested redesigns reduce several
      hemodynamic parameters (i.e., the WSSG, WSSAG, and normal pressure gradient
      [NPG]), thereby reducing the likelihood of restenosis, especially near the
      critical toe region.

PMID- 11321643
TI  - Methods for photoultrasonic treatment of festering wounds in oncological
      patients.
AB  - This article presents further developments of photoultrasonic medical technology.
      It also analyzes its major effects and considers the most promising application
      of this combined technology in medicine, with particular emphasis given to the
      bactericidal treatment of infectious wounds. Moreover, this article describes the
      preliminary experimental results of the aforementioned technology.

PMID- 11321644
TI  - Investigation of brain potentials in sleeping humans exposed to the
      electromagnetic field of mobile phones.
AB  - An investigation was made of 8-hour EEG tracings of sleeping humans exposed to
      the electromagnetic field of a GSM-standard mobile phone. To analyze the EEG
      patterns, manual scoring, nonlinear dynamics, and spectral analysis were
      employed. It was found that, when human beings were exposed to the
      electromagnetic field of a cellular phone, their cerebral cortex biopotentials
      revealed an increase in the alpha-range power density as compared to the placebo
      experiment. It was also found that the dimension of EEG correlation dynamics and
      the relation of sleep stages changed under the influence of the electromagnetic
      field of a mobile phone.

PMID- 11321645
TI  - Effect of alpha-amino acids on the interaction of millimeter waves with water.
AB  - This article tackles the problem of primary reception of millimeter waves by live
      systems. It also discusses the physical mechanisms of low-intensity millimeter
      wave effect on live systems. It is postulated that water molecules of the skin
      can be the primary molecular receptors that transfer the energy of external
      radiation to primary physiological targets in the exposure site (a "water-primary
      target" model). The effect of solute molecules on the absorption of millimeter
      wave radiation (lambda= 2, 5.84, and 7.12 mm) by aqueous solutions was studied on
      alpha-amino acids. Various mechanisms are outlined of intermolecular interaction
      of alpha-amino acids in aqueous solutions, such as the raised absorption of water
      molecules in solute hydration shells (negative hydration) and the decreased
      absorption of water molecules in solute hydration shells (positive hydrophilic
      and hydrophobic hydration).

PMID- 11321646
TI  - Laser non-contact drug delivery methods: mathematical and experimental
      substantiation.
AB  - This article outlines the existing methods for parenteral drug delivery. It also
      presents novel alternative methods based on laser technologies, namely laser
      impregnation and laser injection. A mathematical model is constructed to
      calculate laser impregnator's technical parameters, such as the energy density of
      laser radiation, pulse duration, and pulse repetition frequency. This model also
      makes it possible to estimate the increase in the diffusion rate of drug
      preparations when they are impregnated through multilayer structures, such as the
      skin. Moreover, this article presents experimental results on Er:YAG laser
      injection of various drug media, such as spirit solutions, aqueous solutions, and
      ointments. These preparations were injected into gelatinous gel and autopsy skin
      samples. Possible clinical application is considered for these laser
      transcutaneous drug delivery methods.

PMID- 11321647
TI  - Automatic checkout systems to monitor driver's vigilance.
AB  - A concept for designing automatic checkout systems to prevent drivers from
      falling asleep is presented. It is shown that such systems should use the
      frequency of electrodermal reactions (EDR), which is governed by changes in skin
      resistance. Such changes have a time constant of several seconds. To detect these
      reactions, a special technique was developed. Experimental investigations yielded
      the quantitative characteristics of EDR changes associated with decreased
      vigilance. It was found that, when a person started to fall asleep, the EDR
      frequency diminished. An EDR-based system was developed to assess the alertness
      level. Such a system may be employed to prevent drivers from falling asleep.

PMID- 11321648
TI  - Effect of geomagnetic storms on the erythrocyte sedimentation rate in ischemic
      patients.
AB  - The dynamics of the erythrocyte sedimentation rate (ESR) in patients with
      ischemic disease shows a significantly different pattern in the days of raised
      geomagnetic activity as compared to quiet days. This is revealed by a greater
      intensity of ESR variations during geomagnetic storms as compared to the days of
      when there was little or no sun activity (quiet sun). Such behavior of red blood
      cells reflects the patient's individual sensitivity to geomagnetic field
      fluctuations. This article discusses a possible mechanism of ESR variations.

PMID- 11321649
TI  - Technical aspects of electromagnetic hyperthermia in medicine.
AB  - This article considers the fundamental advantages of electromagnetic hyperthermia
      over different techniques for heating the human being's body. It also presents
      basic parameters that characterize hyperthermia and electromagnetic techniques
      for heating biological tissues. Apart from that, engineering solutions directed
      at providing effective hyperthermia are outlined.

PMID- 11321650
TI  - Effect of low-energy and high-peak-power nanosecond pulses of microwave radiation
      on malignant tumors.
AB  - This article presents the results of experimental investigations of the
      inhibitory effect of low-energy and high-peak-power nanosecond microwave pulses
      on the growth of malignant tumors. From the results obtained, it was concluded
      that these microwave pulses can serve as a promising means for treating malignant
      diseases.

PMID- 11321651
TI  - Long-term control for a retroperitoneal metastasis of malignant gastrointestinal
      stromal tumor after chemoradiotherapy and immunotherapy.

PMID- 11321652
TI  - Polarographic pO2 measurements of intra-abdominal adenocarcinoma in connection
      with intraoperative radiotherapy before and after change of oxygen concentration
      of anaesthetic gases.

PMID- 11321653
TI  - Does radiotherapy have to justify its use in Hodgkin's disease?

PMID- 11321654
TI  - Sino-nasal cancer in Denmark 1982-1991--a nationwide survey.
AB  - Cancer of the nasal cavity and paranasal sinuses is a rare disease. The many
      different histologies and sites make the management of this disease a challenge.
      The current report from the Danish Society for Head and Neck Oncology comprises a
      joint analysis of five retrospective series covering the entire country, with 315
      patients seen in the 10-year period from 1 January 1982 to 31 December 1991.
      Tumour sites were nasal cavity (n = 156), maxillary sinus (n = 139), ethmoid
      sinus (n = 14), sphenoid sinus (n = 5) and frontal sinus (one case). The most
      common histologies included squamous cell carcinoma (126 cases), adenocarcinoma
      (41 cases), malignant melanoma (38 cases) and malignant lymphoma (34 cases). A
      total of 284 patients (90%) received treatment with curative intent; most of
      these patients were treated with radiotherapy, either alone (120 patients) or in
      combination with surgery (111 patients). There was no significant difference
      between the five centres in disease specific survival and overall survival. The
      results showed that histology, localization and nodal involvement were
      significant prognostic factors for locoregional control and survival. Patients
      with squamous cell carcinoma had a significantly poorer prognosis compared with
      patients with adenocarcinoma. However, a Cox multivariate analysis revealed that
      this was likely the result of tumour localization, as most adenocarcinomas were
      in the nasal cavity. The experience from this data collection has inspired the
      Danish Society for Head and Neck Oncology to arrange common data registration of
      several other clinical head and neck series. In the future, the Society plans to
      expand this activity further.

PMID- 11321655
TI  - Outcome of ipsilateral treatment for patients with metastases to neck nodes of
      unknown origin.
AB  - It is not uncommon for head and neck cancer patients to present with neck node
      metastases. Standard treatment for patients in whom no primary tumor is found
      include surgery and radiotherapy but there is still controversy about the type
      and extent of treatment. A retrospective review was carried out on 51 consecutive
      patients with cervical lymph node metastases of unknown origin, treated between
      1980 and 1994 at Radiumhemmet, Karolinska Hospital. All patients received
      radiotherapy to the ipsilateral neck and the corresponding mucosa and surgery was
      performed in 55% of cases. The 5-year overall survival rate was 41%. A primary
      tumor was later found in 6 cases (12%). Two cases of cancer were detected after 5
      years and classified as 'second primaries'. Results from this small retrospective
      material have to be interpreted with caution but indicate that limited,
      ipsilateral radiotherapy to mucosa and lymph nodes combined with surgery, when
      possible, may be justified.

PMID- 11321656
TI  - Sphincter-conserving treatment of carcinomas of the anal margin.
AB  - Between April 1982 and December 1997 24 patients with carcinoma of the anal
      margin were treated with radiation therapy (RT) (10 patients) or RT-chemotherapy
      (CT) (14 patients). External beam RT (EBRT) was delivered in 18 patients,
      combined with brachytherapy in 5 patients, while one patient was treated with
      brachytherapy alone. Inguinal nodes were irradiated in 17 patients. Chemotherapy
      was based on 5-fluorouracil and mitomycin-C. At 5 years, the overall survival
      rate was 56% and the locoregional rate was 69.5%. Anal sphincter was preserved in
      16/24 treated patients. Grade 4 late complications were observed in 3 patients.
      This study reinforces the notion that radical RT +/- CT provides a high
      probability of cure and sphincter preservation in patients presenting with this
      rare condition. Major late toxicity is uncommon; a better adaptation of treatment
      technique to the individual clinical situation may prevent some of the more
      severe complications in the future.

PMID- 11321657
TI  - Management of persistent or locally recurrent epidermoid cancer of the anal canal
      with abdominoperineal resection.
AB  - We retrospectively evaluated the outcome of 22 patients with epidermoid cancer of
      the anal canal who underwent surgical salvage after failure of primary
      chemoradiotherapy. Patients who required surgery had significantly more advanced
      T-stage than those who did not fail chemoradiotherapy. Eighteen patients failed
      surgical salvage. Invasion through the muscle wall of the bowel was present in 16
      of 18 patients compared with two of four patients who have no evidence of disease
      (follow-up 5-10 years). Failure occurred only in the pelvis in 13 of the patients
      who died of disease. The mean time to death after surgery was 19 months. We
      confirm the overall poor results of conventional abdominoperineal resection in
      those patients who have failed previous therapy. Most failures occur in the
      pelvis. Transanorectal ultrasound and magnetic resonance imaging (MRI) may allow
      better selection of patients for exenterative procedures and identify those not
      amenable to successful salvage.

PMID- 11321658
TI  - Dimensions of fatigue during radiotherapy--an application of the Swedish
      Occupational Fatigue Inventory (SOFI) on cancer patients.
AB  - The aims of this study were primarily to evaluate the applicability of the
      Swedish Occupational Fatigue Inventory (SOFI) on cancer patients, secondly to
      describe the development of fatigue in patients, receiving full dose radiotherapy
      with a curative intent. A questionnaire was completed by 81 cancer patients at
      four occasions; before treatment. during the last week of treatment. 1 and 3
      months, respectively, after treatment. The fatigue increased significantly at the
      end of treatment, as compared to pretreatment, and decreased after treatment. The
      highest fatigue ratings concerned lack of energy, lack of motivation and
      sleepiness. The five SOFI-dimensions explained more than half of the variance in
      the overall rating of fatigue, and the internal consistency of the dimensions
      were good. However, the ratings were on the lower part of the scale and the
      dimensions correlated more than expected. Thus, the relevance of the SOFI for use
      also among patients is only partially supported, and studies with larger samples
      are needed for further testing of the inventory.

PMID- 11321659
TI  - Survivors of childhood cancer for more than twenty years.
AB  - Present health status, complications, and development of long-term survivors of
      childhood cancer followed for more than 20 years in a single institution were
      reviewed. The departmental database was searched to identify patients diagnosed
      with childhood cancer and consequently treated between 1965 and 1978. A total of
      124 (77%) long-term survivors participated on a voluntary basis in the study. A
      semi-standardized interview consisted of measures evaluating the present health
      condition, sequelae of treatment, second malignancies, intellectual development
      and presence of offspring of the former patients. The majority of patients were
      treated with chemotherapy (82%). 67% received radiotherapy and 67% underwent
      surgery. A relapse of the primary tumor was diagnosed in four patients as well as
      a second malignancy in four other patients. In 33% of the long-term survivors one
      or more serious therapy-related health problems were noted. Adequate mental and
      intellectual development was achieved in 65%. Children treated in the early years
      of pediatric oncology seem to have a satisfactory outcome as viewed over the long
      term. Consequent ongoing follow-up is still necessary to detect health problems
      and enhance quality of life for subsequent generations of children with cancer.

PMID- 11321660
TI  - Breast cancer surgery--historical evolution, current status and future
      perspectives.
AB  - The diagnosis and management of breast cancer have changed dramatically over the
      past two decades in response not only to new technologies but also to cultural
      and social aspects of the discase. Mastectomy (either radical or modified
      radical) was the historical mainstay of the treatment of breast cancer for
      decades. Although mastectomy continues to be appropriate for some patients,
      breast conservation has become the preferred method of treatment for many
      patients. Meeting the dual goal of optimum cosmesis and minimal rates of in
      breast recurrences after breast-conservation therapy requires the selection and
      integration of appropriate diagnostic methods (including breast imaging
      techniques and breast biopsy techniques) its well as therapeutic methods (breast
      irradiation techniques, and systemic cytotoxic and hormonal therapy). To achieve
      optimal breast-conservation treatment, a multidisciplinary approach is
      neccessary. Mastectomy followed by breast reconstruction is a valuable
      alternative for patients who require or choose mastectomy. After tumor
      downstaging with induction chemotherapy, a large percentage of patients with
      large or locally advanced tumors will be able to undergo breast-conservation
      therapy Partial (levels I and II) axillary lymph node dissection remains the
      standard of care in the surgical management of patients with invasive breast
      cancer. Recently there has been intense interest in selective axillary lymph node
      dissection, focused mainly on the identification of patients who are likely to
      benefit from axillary lymph node dissection, using sentinel lymph node biopsy.

PMID- 11321661
TI  - Quality  assurance in radiotherapy of breast cancer--variability in planning
      target volume delineation.
AB  - The inter-physician and inter-patient variability in planning target volume
      delineation for the radiotherapy of breast cancer after conservative surgery is
      presented. Eleven experienced radiation oncologists determined the planning
      target volume (PTV) for four breast cancer patients. Delineation was based on CT
      slices taken at intervals of 15 mm. The variability in target volume delineation
      was determined by measuring the volumes in units of cc and the position of the
      drawn PTVs. Statistical analysis was based on X/R-charts and on Pareto chart and
      analysis. The maximum range in PTV for one patient was from 670 to 1,200 cc. The
      observations of three physicians were in excess of the warning limit altogether
      18 times. The methods used in this study clearly reveal inter-physician
      variability in PTV delineation and widest variations found are not acceptable.
      Training targeted to some physicians and more detailed and unambiguous protocols
      for PTV delineation are needed.

PMID- 11321662
TI  - Protein accumulation and gene mutation of p53 in bilateral breast cancer. South
      East Sweden Breast Cancer Group.
AB  - The aim of this study was to investigate the frequency of p53 alterations in
      bilateral breast cancer and to evaluate a possible clonal relationship between
      the paired tumours regarding p53 alteration and other pathobiological variables.
      Tumours from 34 patients were investigated with immunohistochemistry, single
      strand conformation polymorphism analysis and DNA-sequence analysis applied to
      exons 5-8. Fifteen percent of the 68 tumours showed positive immunoreaction
      and/or presence of mutation. The occurrence of p53 accumulation was 9% and the
      prevalence of gene mutation 10%. No significant concordance was found between the
      tumours in the same patient for p53 alterations, progesterone receptor status or
      DNA ploidy. S-phase fraction showed a weak correlation, not statistically
      significant. Oestrogen receptor status was the only variable that exhibited a
      significant concordance. No convincing evidence was found for other associations
      between the paired tumours or for a high prevalence of p53 alterations in
      bilateral breast cancer.

PMID- 11321663
TI  - Dual modulation of UFT with leucovorin and hydroxyurea in metastatic colorectal
      cancer.
AB  - The aim of the study was to investigate the possibility of dual modulation of UFT
      with leucovorin and hydroxyurea in a phase II trial of metastatic colorectal
      cancer. A total of 77 patients with measurable disease were included. UFT (300
      mg/m2) was given with a fixed dose of 1-leucovorin (22.5 mg daily) and
      hydroxyurea (0.5 g daily) for 28 days followed by a 7 days' rest period.
      Treatment continued until progression or unacceptable toxicity. Sixty-three
      patients were evaluable for response. One patient (1.6%) had a complete remission
      and 13 (20.6%) a partial response for an overall response rate of 22.2%. The
      treatment was well tolerated. No significant bone marrow depression occurred.
      Grade 2 gastrointestinal toxicity was recorded in 28.5% of the patients, and
      grade 3 in 12.9%. The median time to progression was 6.8 months and the median
      crude survival was 11 months. In conclusion, hydroxyurea did not appear to
      increase either the response rate or the toxicity. Phase III trials along the
      same line cannot be recommended.

PMID- 11321664
TI  - Effect of obesity on the leukocyte nadir in women treated with adjuvant
      cyclophosphamide, methotrexate, and fluorouracil dosed according to body surface
      area.
AB  - Chemotherapy doses are sometimes reduced because of obesity in patients. This
      study examines the effect of parameters reflecting the body size, body weight and
      height, body mass index (BMI), and body surface area (BSA) on the depth of the
      blood leukocyte nadir in breast cancer patients receiving adjuvant chemotherapy,
      when drug dosing was based on the BSA. Three hundred and forty patients with node
      positive breast cancer without distant metastases were treated with 6 cycles of
      adjuvant postoperative CMF (cyclophosphamide 600 mg/m2, methotrexate 40 mg/m2,
      and 5-fluorouracil 600 mg/m2 i.v. every 3 weeks). Patients within the highest BMI
      had the highest leukocyte nadir values (Spearman correlation coefficient 0.3, p <
      0.001). A high body weight and a large BSA were also associated with high
      leukocyte nadirs. We conclude that when the blood leukocyte nadir is used as a
      surrogate marker for the drug effect, obese patients receiving intravenous CMF
      have higher leukocyte nadirs than the lean ones. Therefore, the drug doses should
      not be reduced because of obesity, and even when obese patients are treated
      according to the scheduled doses they may remain slightly underdosed.

PMID- 11321665
TI  - Superficial inguinal and radical ilioinguinal lymph node dissection in patients
      with palpable melanoma metastases to the groin--an analysis of survival and local
      recurrence.
AB  - The present study addresses the question whether an extended ilioinguinal
      dissection as compared to an only superficial inguinal dissection improves
      survival and/or local tumour control after the appearance of palpable melanoma
      metastases to the groin. We retrospectively analysed the data of 104 patients
      with 69 ilioinguinal and 35 superficial inguinal dissections (median follow up
      127 months). Prognostic factors of survival and groin recurrence were assessed
      using Kaplan-Meier estimation and Cox proportional hazards model. By
      multifactorial analysis, metastatic involvement of two lymph nodes or less was
      associated with a significantly better survival rate than involvement of > 2 or
      pelvic nodes (p = 0.0002). After radical ilioinguinal dissection, patients with
      extremity-located primaries had a better prognosis than patients with truncal
      primaries (p = 0.03). Tumour infiltration of the ilio-obturator compartment was
      found to be an independent factor of poor prognosis (p = 0.0009). The probability
      of recurrence in the dissected groin paralleled the number of positive nodes and
      significantly increased if intransits were observed (p = 0.0002). The extent of
      surgery, Breslow thickness, epidermal ulceration, sex, age and adjuvant
      chemotherapy neither significantly influenced survival nor local control rates.
      In summary, when metastatic inguinal nodes become palpable, the presence of
      pelvic metastases indicates systemic disease. After therapeutic groin dissection,
      local recurrence and survival depend rather on regional tumour burden than on the
      extent of surgery.

PMID- 11321666
TI  - Mediastinoscopy--its role and value today in the differential diagnosis of
      mediastinal pathology.
AB  - Mediastinoscopy has been an important method in the differential diagnosis of
      mediastinal pathology since it was presented by Carlens in 1959. Present
      investigation methods in radiology such as computed tomography and magnetic
      resonance imaging as well as the new developments in ultrasonography have
      resulted in a decrease in the number of mediastinoscopies performed. In addition,
      better results of fine-needle aspiration and core-needle biopsy investigations
      together with new techniques in thoracoscopy have brought alternative
      possibilities in examining mediastinal masses. To evaluate the role of
      mediastinoscopy today, a retrospective study was conducted comprising 249
      consecutive patients who had undergone mediastinoscopy in the years 1989 1997 at
      Turku University Central Hospital. Mediastinoscopy was technically possible in
      229 of the 249 cases (92.0%) and a definitive diagnosis was obtained in 210 cases
      (84.3%). The mortality rate was zero and only 13 complications (5.2%) were
      reported. Six cases of paresis of the left recurrent nerve were reported, four of
      which were temporary. There were also five minor intraoperative and two
      postoperative bleedings, which were easily controlled. We still consider
      mediastinoscopy as a safe and efficient way of examining mediastinal pathology.

PMID- 11321667
TI  - Increased serum cortisol levels are associated with high tumour grade in patients
      with renal cell carcinoma.
AB  - Cortisol and dehydroepiandrosterone (DHEA) and its sulphate (DHEAS) are the major
      steroid hormones produced by the human adrenal cortex. The serum levels of
      cortisol and DHEAS were analysed in 211 consecutive patients with renal cell
      carcinoma before initiation of therapy. Serum cortisol was significantly higher
      in patients with renal cell carcinoma compared with that in patients with benign
      cysts (p < 0.0001). Serum cortisol was independent of disease stage, but
      positively correlated to tumour diameter and grade. The serum levels of DHEAS
      were higher in men than in women, and decreased with age, but did not correlate
      with disease stage, tumour diameter or grade. The prognosis of patients with
      elevated serum cortisol tended to be poorer (p = 0.06) than the prognosis of
      those with lower levels. In a multivariate analysis, disease stage and tumour
      grade were independent predictors of prognosis. Age, gender and serum levels of
      cortisol and DHEAS were of limited value for prognosis.

PMID- 11321668
TI  - Always on a Friday? Time pattern of referral for spinal cord compression.
AB  - For patients with spinal cord compression, radiotherapy should be initiated as
      soon as possible to optimize the chances for restoration of neurological
      function. The speed of referral in the region of our radiotherapy institution
      with nine general hospitals was analysed based on a tumour and treatment-related
      registry. From January 1987 to December 1997, 443 patients were treated. All
      patients were seen and treated on the day of referral. Significantly more
      referrals took place on Friday, 30%, compared with 12% on Monday, 17% on Tuesday,
      15% on Wednesday, 20% on Thursday, 5% on Saturday and 1% on Sunday (p < 0.002).
      This difference was the same for patients whether they were formerly treated in
      our institution (n = 242) or not (n = 201). No significant difference was found
      between different categories of patients (p = 0.28). These data are discussed
      with the referring physicians to encourage speed of diagnosis and referral.

PMID- 11321669
TI  - Comparison of different cell-cluster models for cell-level dosimetry.
AB  - An important factor in dose calculations for targeted radionuclide therapy is the
      cell-cluster model used. We developed a cell-cluster model based on optimization
      through mechanical hard-sphere collisions. The geometrical properties and the
      dosimetric effects of the new model were compared with those of two previous
      models, i.e. the traditional lattice model and our CellPacker model in which the
      cells are individually and systematically piled as a cluster. The choice of the
      cell-cluster model has an effect on the calculated mean absorbed doses in the
      cells. While CellPacker produces clusters with distinct tumour-healthy tissue
      interface, our new model is able to make the interface diffuse. Outside the
      interface the new model is capable to pack cells tighter than CellPacker enabling
      the description of tissues of higher cellular density. Our two cluster models
      make it possible to construct the cluster model according to the tissue in
      question.

PMID- 11321670
TI  - Impacts of elevated level of hCG in serum on clinical course and radiotherapy
      results in the histology-confirmed intracranial germinomas.
AB  - The prognosis of intracranial germinoma producing the human chorionic
      gonadotropin (hCG) is controversial due to limited information. We undertook a
      retrospective analysis to determine whether this type of tumor has similar
      clinical course and prognosis to hCG non-secreting germinoma. Thirty-one
      histologically confirmed intracranial germinoma patients who had pretreatment hCG
      examination in serum/CSF were treated with radiotherapy between 1980 and 1996.
      hCG level was measured by immunoradioassay of beta subunit of hCG. Six patients
      had elevated serum hCG levels and were defined as having hCG secreting germinoma.
      All except three patients received craniospinal axis irradiation. The follow-up
      ranged from 19-175 months with a median of 63 months. hCG secreting germinoma
      accounted for 19% of intracranial germinoma cases. Elevated hCG levels ranged
      from 39-260 IU/l in serum. No difference was found between hCG non-secreting
      germinoma and hCG secreting germinoma in terms of patient or treatment
      characteristics. There was no recurrence among the six hCG secreting germinoma
      patients. The 5-year overall and disease-free survival rates were 96% for
      patients with hCG non-secreting germinomas and 100% for the patients with hCG
      secreting germinomas. The survival difference was not significant (p = 0.59). Our
      results suggest that elevated level of hCG did not result in any differences in
      the clinical characteristics or survival after radical radiotherapy in
      histologically confirmed intracranial germinoma.

PMID- 11321671
TI  - The electrochemically induced conformational transition of disulfides in bovine
      serum albumin studied by thin layer circular dichroism spectroelectrochemistry.
AB  - The conformational transition of disulfides in bovine serum albumin (BSA) induced
      by electrochemical redox reaction of disulfides were monitored by in-situ
      circular dichroism (CD) spectroelectrochemistry, with a long optical path thin
      layer cell and analyzed by a singular value decomposition least square (SVDLS)
      method. Electrochemical reduction of disulfides drives the left-handed
      conformation of disulfides changed into the right-handed. At open circuit, eight
      of the 17 disulfides were of left-handed conformation. Four of the 17 disulfides
      took part in the electrochemical reduction with an EC mechanism. Only one-fourth
      of the reduced disulfides returned to left-handed conformation in the re
      oxidation process. Some parameters of the electrochemical reduction process, i.e.
      the number of electrons transferred and electron transfer coefficient, n = 8,
      alpha n = 0.15, apparent formal potential, E1(0') = -0.65(+/-0.01) V, standard
      heterogeneous electron transfer rate constant, k1(0) = (2.84 +/- 0.14) x 10(-5)
      cm s(-1) and chemical reaction equilibrium constant, Kc = (5.13 +/- 0.12) x 10(
      2), were also obtained by double logarithmic analysis based on the near-UV
      absorption spectra with applied potentials.

PMID- 11321672
TI  - Birhythmicity, trirhythmicity and chaos in bursting calcium oscillations.
AB  - We have analyzed various types of complex calcium oscillations. The oscillations
      are explained with a model based on calcium-induced calcium release (CICR). In
      addition to the endoplasmic reticulum as the main intracellular Ca2+ store,
      mitochondrial and cytosolic Ca2+ binding proteins are also taken into account.
      This model was previously proposed for the study of the physiological role of
      mitochondria and the cytosolic proteins in gene rating complex Ca2+ oscillations
      [1]. Here, we investigated the occurrence of different types of Ca2+ oscillations
      obtained by the model, i.e. simple oscillations, bursting, and chaos. In a
      bifurcation diagram, we have shown that all these various modes of oscillatory
      behavior are obtained by a change of only one model parameter, which corresponds
      to the physiological variability of an agonist. Bursting oscillations were
      studied in more detail because they express birhythmicity, trirhythmicity and
      chaotic behavior. Two different routes to chaos are observed in the model: in
      addition to the usual period doubling cascade, we also show intermittency. For
      the characterization of the chaotic behavior, we made use of return maps and
      Lyapunov exponents. The potential biological role of chaos in intracellular
      signaling is discussed.

PMID- 11321673
TI  - Partition coefficients of beta-blockers in bile salt/lecithin micelles as a tool
      to assess the role of mixed micelles in gastrointestinal absorption.
AB  - The objective of this study was to develop non-invasive spectroscopic methods to
      quantify the partition coefficients of two beta-blockers, atenolol and nadolol,
      in aqueous solutions of bile salt micelles and to assess the effect of lecithin
      on the partition coefficients of amphiphilic drugs in mixed bile salt/lecithin
      micelles, which were used as a simple model for the naturally occurring mixed
      micelles in the gastrointestinal tract. The partition coefficients (Kp) at 25.0
      +/- 0.1degreesC and at 0.1 M NaCl ionic strength were determined by
      spectrofluorimetry and by derivative spectrophotometry, by fitting equations that
      relate molar extinction coefficients and relative fluorescence intensities to the
      partition constant Kp. Drug partition was controlled by the: (i) drug properties,
      with the more soluble drug in water (atenolol) exhibiting smaller values of Kp,
      and with both drugs interacting more extensively in the protonated form; and by
      (ii) the bile salt monomers, with the dihydroxylic salts producing larger values
      of Kp for the beta-blockers, and with glycine conjugation of the bile acid
      increasing the values of Kp for the beta-blockers. Addition of lecithin to bile
      salt micelles decreases the values of Kp of the beta-blockers. Mixed micelles
      incorporate hydrophobic compounds due to their large size and the fluidity of
      their core, but amphiphilic drugs, for which the interactions are predominantly
      polar/electrostatic, are poorly incorporated in mixed micelles of bile
      salts/lecithin.

PMID- 11321674
TI  - Concerted motions in copper plastocyanin and azurin: an essential dynamics study.
AB  - Essential dynamics analysis of molecular dynamics simulation trajectories (1.1
      ns) of two copper containing electron transfer proteins, plastocyanin and azurin,
      has been performed. The protein essential modes have been analysed in order to
      identify large concerted motions which could be relevant for the electron
      transfer function exerted by these proteins. The analysis, conducted for temporal
      windows of different lengths along the protein trajectories, shows a rapid
      convergence and indicates that for both the proteins the predominant internal
      motions occur in a subspace of only a few degrees of freedom. Moreover, it is
      found that for both the proteins the likely binding sites (i.e. the hydrophobic
      and negative patches) with the reaction partners move in a concerted fashion with
      a few structural regions far from the active site. Such results are discussed in
      connection with the possible involvement of large concerted motions in the
      recognition and binding interaction with physiological electron transfer
      partners.

PMID- 11321675
TI  - Interaction of Zn2+ with phospholipid membranes.
AB  - To characterize the specificity of zinc binding to phospholipid membranes in
      terms of headgroup structure, hydration and phase behavior we studied the
      zwitterionic lipid 1-palmitoyl-2-oleoyl-phosphatidylcholine as a function of
      hydration at 30 degreesC in the presence and absence of ZnCl2. Zinc forms a 2:1
      1:1 complex with the lipid, and in particular with the negatively charged
      phosphate groups. Zn2(+)-bridges between neighboring lipid molecules stabilize
      the gel phase of the lipid relative to the liquid-crystalline state. Upon Zn2+
      binding the C-O-P-O-C- backbone of the lipid headgroup changes from a
      gauche/gauche into the trans/trans conformation and it loses roughly 50% of the
      hydration shell. The ability of the Zn2(+)-bound phosphate groups to take up
      water is distinctly reduced, meaning that the headgroups have become less
      hydrophilic. The energetic cost (on the scale of Gibbs free energy) for
      completely dehydrating the lipid headgroups is decreased by approximately 10
      kJ/mole in the presence of Zn2+. The interaction of phospholipid headgroups with
      Zn2+ is conveniently described by a hydrated zinc-phosphate complex the key
      energy contribution of which is more covalent than electrostatic in nature.
      Dehydration of phospholipid headgroups due to complexation with zinc cations is
      suggested to increase fusogenic potency of lipid membranes. Zinc appears to be
      one of the most potent divalent cation in inducing membrane fusion.

PMID- 11321676
TI  - Interactions of cyclic AMP and its dibutyryl analogue with model membrane: X-ray
      diffraction and Raman spectroscopic study using cubic liquid-crystalline phases
      of monoolein.
AB  - Interactions of adenosine 3':5'-cyclic monophosphate (cAMP) and its dibutyryl
      analogue, N6,2'-O-dibutyryladenosine 3':5'-cyclic monophosphate (dbcAMP), with a
      lipid bilayer were studied by small-angle X-ray diffraction (SAXD) and Raman
      spectroscopy. The cubic Pn3m phase of monoolein (MO) served as a bilayer-based
      model system. SAXD measurements have indicated that incorporation of
      approximately 3 wt.% cAMP leaves the phase parameters practically unaltered,
      whereas the same content of dbcAMP induces the intercubic Pn3m-->Ia3d transition.
      By applying the concepts of lipid shape parameter and infinite periodic minimal
      surface to these MO phases, we have suggested that, as opposed to cAMP, dbcAMP
      associates with the MO bilayer. This conclusion has been supported by the
      different effects of phase matrix on the Raman shifts of the adenine and
      phosphate vibrational modes of these two nucleotides. Moreover, Raman spectra
      have indicated that dbcAMP inserts into the bilayer through the butyryladenine
      group, positioning dbcAMP preferentially at the polar/apolar interface.

PMID- 11321677
TI  - Thermodynamics of Na+ binding to coagulation serine proteases.
AB  - The sodium binding to serine proteases triggers a conformational change in the
      proteins that enhances the catalytic activity of the enzymes. The interaction of
      the cation with the protein is mediated by the hydrogen-bonding network of water
      molecules that embed the Na+ site. We pointed out the crucial role of the
      insertion loop 186a-d and the I16-D194 ion pair in the stabilization of sodium
      binding pocket in thrombin. This paper contributes to better explain the
      molecular mechanism of sodium binding for different serine proteases leading to
      the identification of the structural changes necessary to engineer a functional
      Na+ site and regulate catalytic activity in serine proteases.

PMID- 11321678
TI  - Conformation of NADH studied by fluorescence excitation transfer spectroscopy.
AB  - Dihydronicotinamide adenine dinucleotide (NADH), is known to stack in two
      limiting conformations. Surprisingly, previous experimental work on NADH has not
      clearly defined whether this folding and unfolding process can be described as
      first order (involving only two states) or whether one or more intermediates must
      be included in the description. In addition, a large disparity exists between
      reported equilibrium constants for the aqueous solution at room temperature.
      Using methanol as a denaturant, we have used fluorescence excitation transfer
      spectroscopy to probe the stacking/un-stacking equilibrium. Our results can be
      represented using a simple two state model. Furthermore, the mole fraction of
      aqueous NADH in the stacked configuration is significantly higher than previously
      reported. Using a thermodynamic two state model, we have determined
      deltaG(o)(H2O) = 8.8 +/- 1.4 kJ mol(-1). From excitation energy transfer
      measurements the fraction of NADH in the folded form at 295 K was determined to
      be 0.55.

PMID- 11321679
TI  - The catalytic efficiency of soybean lipoxygenase-1 is enhanced at low gravity.
AB  - Several cellular processes are modified when cells are placed under conditions of
      weightlessness. As yet, there is no coherent explanation for these observations,
      nor it is known which biomolecules might act as gravity sensors. Lipoxygenases
      generate leukotrienes and lipoxins from arachidonic acid, being responsible for
      many pharmacological and immunological effects, some of which are known to be
      affected by microgravity. In the course of the 28th parabolic flight campaign of
      the European Space Agency we measured the activity of pure soybean lipoxygenase-1
      on linoleic acid, by a fibre optics spectrometer developed on purpose. It was
      found that microgravity reduced the apparent Michaelis-Menten constant (Km) of
      the enzymatic reaction to one fourth with respect to the 1 g control, whereas,
      the catalytic constant (k(cat)) was unaffected. Consequently, the catalytic
      efficiency of lipoxygenase-1 (k(cat)/Km) was approximately four-fold higher in
      flight than on ground. This unprecedented finding suggests that lipoxygenase-1
      might be a molecular target for gravity.

PMID- 11321680
TI  - The magnitude of fear of adverse effects as a reason for nonparticipation in drug
      treatment: a short review.
AB  - The extent and reasons for nonparticipation in preventive drug intervention
      programs were reviewed. Special attention was paid to the magnitude of "steroid
      phobia" in cases of early treatment of asthma patients, with inhaled steroids. A
      Medline search yielded 11 studies. One study addressed the topic of treatment,
      with inhaled steroids, in early asthma patients. Nonparticipation rates to
      "early" drug treatment ranged from 0.3% to 48%. Fear of adverse effects and lack
      of knowledge about the treatment were given as the most important reasons for
      nonparticipation. Educational measures to increase knowledge about the drug were
      advised by most of the authors. In the asthma study a specific "steroid-phobia"
      was not indicated, possibly due to the continuous education about the steroid
      treatment throughout the study. Proper and repeating information about the safety
      and the minimal adverse effects of preventive drug treatment, especially inhaled
      steroids, seems essential to improve the treatment rate.

PMID- 11321681
TI  - Asthma diagnosis and management in adults: is the risk of underdiagnosis and
      undertreatment related to patients' education levels?
AB  - To determine the relationship between patient education and the risk of
      underdiagnosis and undertreatment of asthma, a cross-sectional study of 500 (250
      males and 250 females) adult attendees between 16 and 44 years of age was
      undertaken at five primary health care (PHC) centers in Al-Ain, United Arab
      Emirates. We used an Arabic translation of the European Community Respiratory
      Health Survey Screening Questionnaire. Asthmatics with higher levels of education
      had a significantly higher risk of underdiagnosis and undertreatment than
      asthmatics with less education. Doctors at PHC centers railed to diagnose 34.6%
      of the asthmatics with lower levels of education and 77.6% of the patients with
      higher levels of education. Eighty-five percent of the asthmatics with lower
      levels of education and 46.6% of the asthmatics with higher levels of education
      recognized that they had asthma. Thirty-eight percent of the asthmatics with
      lower levels of education and 83% of the asthmatics with higher levels of
      education were undertreated. It was found that 19% of the asthmatics with lower
      levels of education and 3% of the asthmatics with higher level of education were
      on prophylactic medication for asthma. We concluded that education level was
      related to underdiagnosis and undertreatment of asthma among adults between 16
      and 44 years of age. People with higher levels of education have a higher risk of
      underdiagnosis and undertreatment than do those with lower levels of education.
      The factors that might be associated with these findings need to be explored in
      further studies.

PMID- 11321682
TI  - Inaccuracy of "personal best" peak expiratory flow rate reported by inner-city
      patients with acute asthma.
AB  - Percent predicted peak expiratory flow (PEF) is used to determine the severity of
      asthma exacerbation and the appropriateness of discharge from the emergency
      department (ED). The 1995 Global Initiative for Asthma and 1997 National Asthma
      Education and Prevention Program guidelines recommend using a patient's "personal
      best" PEF, if available, as a better measurement than the predicted PEF obtained
      from population-based nomograms. We evaluated the accuracy of personal best PEF
      as provided by inner-city ED patients with acute asthma. One hundred four
      patients with acute asthma agreed to return to the ED for repeat PEF measurements
      on days 3, 7, 12, 21, and 24 after their initial ED visits for acute asthma. At
      the ED visit, only 29% (30/104) of patients were able to report a personal best
      PEF. Over the 24 days of follow-up, 45% (10/22) of these patients had a measured
      PEF greater than their reported personal best. If a predicted PEF of at least 70%
      was used as the criterion for ED discharge, as several asthma guidelines
      recommend, then using patients' reported personal best PEF would have led to
      inappropriate ED discharge for some patients.

PMID- 11321683
TI  - Changes in indices of airway hyperresponsiveness during one year of treatment
      with inhaled corticosteroids in patients with asthma.
AB  - We analyzed the changes in indices of airway hyperresponsiveness, including
      hypersensitivity and hyperreactivity, during one year of treatment with inhaled
      corticosteroids. We then investigated on which of them the inhaled
      corticosteroids had a primary effect. Fifty outpatients with asthma were
      recruited and treated with inhaled beclomethasone dipropionate. They underwent
      bronchoprovocation tests on the initial visit and at 3, 6, and 12 months. The
      dose of methacholine required to produce a 20% fall in the forced expiratory
      volume in 1 second (PD20-FEV1) was measured to evaluate airway hypersensitivity.
      A relatively novel index, the percent change in the forced vital capacity
      (deltaFVC%) at the PD20-FEV1, was assessed as a marker of airway hyperreactivity.
      PD20-FEV1 and deltaFVC% were assumed to indicate the horizontal shift of the dose
      response curve and the vertical change in the maximal response plateau,
      respectively. Log(PD20-FEV1) and deltaFVC% continued to improve throughout the
      year (p < 0.001 and p = 0.002, respectively). Log(PD20-FEV1) improved
      significantly at the 3-month evaluation (p < 0.001), and deltaFVC% improved at
      the 6-month evaluation (p = 0.012). Log(PD20-FEV1) had no or weak relationships
      with deltaFVC% at all evaluation points. In conclusion, inhaled corticosteroids
      continued not only to reverse the leftward shift of the curve, but also to
      restore the plateau. Furthermore, their effect was reflected primarily by the
      former rather than the latter: They should be followed separately to examine how
      much airway inflammation is reduced.

PMID- 11321684
TI  - Patient education provided to asthmatic children: a historical cohort study of
      the implementation of NIH recommendations.
AB  - NIH guidelines for treatment of childhood asthma emphasize educating both
      patients and family about avoiding triggers and providing information to support
      self-management of asthma. To determine the extent to which primary care
      providers had implemented these recommendations, we examined the patient
      education provided to a cohort of asthmatic children (n = 331) between January
      and December 1994. During 1994 education of any type was documented for less than
      half the children. Provision of education was associated with asthma severity: An
      action plan for exacerbations was discussed with the majority with moderate or
      severe asthma (61%). Avoiding triggers (aOR: 2.38, 95% CI: 1.37-4.12) and
      treatment goals (aOR: 3.14, 95% CI: 1.46-6.75), were more likely to be discussed
      with children who were prescribed inhaled anti-inflammatory medication, after
      adjustment for asthma severity and age. Limited implementation of the NIH
      recommendations by primary care providers in our study may have reduced their
      impact on the management of childhood asthma.

PMID- 11321685
TI  - Parental smoking and the risk of respiratory symptoms among schoolboys in Al
      Khobar City, Saudi Arabia.
AB  - The objective of this study was to measure the prevalence of parental smoking and
      its association with respiratory symptoms among 6- through 15-year-old schoolboys
      in Al-Khobar City, Saudi Arabia. This was a cross-sectional study. The
      methodology included the distribution of a self-administered questionnaire, which
      was completed by the parents of 1482 schoolboys who satisfied the selection
      criteria of the study. The overall rate of smoking among parents of this sample
      was 18.2% (32% among fathers and 4% among mothers). There was an increased risk
      associated with parental smoking and respiratory symptoms among asthmatic and
      nonasthmatic children. The magnitude of this risk was variable for different
      respirator), symptoms. The smoking rate among parents of asthmatic children was
      significantly higher than that of parents of normal children. The logistic
      regression model showed paternal smoking to be significantly associated with
      asthmatic children. The study concluded that there is an increased risk of
      respiratory symptoms among asthmatic and nonasthmatic children because of
      parental smoking. The smoking rate and trend among fathers and mothers were
      comparable to those reported earlier, indicating an ongoing problem.
      Schoolchildren with smoking parents may be better screened for bronchial asthma.
      Management of children presenting with respiratory symptoms should include an
      inquiry about exposure to passive smoking. Tobacco smoking should be considered a
      public health problem with serious implications, and the importation of tobacco
      should be banned.

PMID- 11321686
TI  - Patterns of inpatient and outpatient care for asthma in Erie and Niagara
      Counties, western New York State.
AB  - The prevalence of asthma, as well as the morbidity and mortality due to asthma,
      has increased in the United States, especially among poor minority
      subpopulations. The causes of these increases are complex and not well
      understood. Our findings from an analysis of emergency room (ER) visits and
      hospitalizations for Erie and Niagara Counties in western New York State for the
      period 1984-1991 provides important background to this problem. Of all
      respiratory disorders, asthma was the most frequent reason for ER visits and was
      second only to pneumonia as a reason for hospital admissions. In Erie County the
      hospitalization rates for asthma in two inner-city communities with predominantly
      minority populations were 1.48 and 2.09 times higher than those in the rest of
      the county. Furthermore, the hospitalization rates for these communities showed
      an increasing trend over the study period. Gender differences were also found.
      Boys age 0 to 9 years were hospitalized for asthma twice as often as girls.
      However, over 15 years of age, females had admission rates that were twice those
      of males. In contrast, hospitalization rates for pneumonia were equal for males
      and females, which would suggest gender differences particular to asthma.
      Hospitalizations for asthma in the western New York region cost an estimated
      $6,000,000 in 1990. We conclude that asthma is a major cause of morbidity in this
      region with excessive and increasing impact on inner-city communities.

PMID- 11321687
TI  - Increasing use of inhaled steroids associated with declining asthma mortality.
AB  - Increasing worldwide asthma prevalence and mortality has led to greater advocacy
      of inhaled agents, especially steroids. To determine whether corresponding drug
      usage trends had ensued locally, wholesale data (expressed as defined daily doses
      (DDDs)/1000 inhabitants/day) were compared for inclusive periods 1984-1986 and
      1992-1994. Whereas absolute usage of anti-asthmatics increased by 79%,
      proportional inhaled usage increased markedly, especially of steroids (571%) and
      in hospitals. An odds ratio trend analysis revealed asthma mortality from 1992
      onward had declined, particularly in males (p < 0.001). In Hong Kong, despite
      increasing asthma prevalence, more intensive use of anti-asthmatic drugs
      (especially inhaled steroids) was associated with declining asthma mortality.

PMID- 11321688
TI  - Developing a community-specific health-related quality of life (HRQOL)
      questionnaire for asthma: the Asthma-Specific Quality of Life Questionnaire for
      Native American Adults (AQLQ-NAA).
AB  - The Asthma Quality of Life Questionnaire for Native American Adults (AQLQ-NAA)
      was developed by modifying the Asthma Quality of Life Questionnaire-Marks (AQLQ
      M) using the focus group technique. The 19-item AQLQ-NAA has emphasis on
      restrictions in social, community, and cultural activities. Higher scores
      indicate a better quality of life. The modified questionnaire was administered to
      a sample of 51 Native American adults with asthma at the Albuquerque USPHS Indian
      Hospital and its affiliated field clinics. Principal components analysis
      identified three domains with eigenvalues greater than 1.00: Community and Social
      Restrictions (CSR), Psychological Impact (PIM), and Symptoms (SYM). Cronbach's
      coefficient alpha for the AQLQ-NAA was 0.95 and ranged from 0.82 to 0.93 for the
      individual domains, indicating good internal consistency. The AQLQ-NAA score
      correlated negatively and significantly to urgent care visits, physician visits,
      and total number of medications taken for asthma in the past 6 and 12 months (p <
      0.05). Additionally, the AQLQ-NAA score was correlated positively and
      significantly to medication adherence in the past 6 and 12 months (p < 0.05).
      Similar patterns of correlations were found with all three domain scores. These
      results indicated that there is evidence for the construct validity of the AQLQ
      NAA and its domains. The AQLQ-NAA should provide a useful measure of HRQOL in
      asthma-specific medical interventions for the population in which it was
      developed.

PMID- 11321689
TI  - Predicting emergency department utilization in adults with asthma: a cohort
      study.
AB  - A consecutive sample of 378 adults with asthma were assessed at a university
      asthma program and then interviewed 1 year later regarding their need for
      emergency department (E.D.) asthma treatment. The purpose of this prospective
      cohort study was to determine whether any of their initial features could predict
      their subsequent need for E.D. asthma treatment. At one year, a total of 73 of
      the subjects had attended emergency departments for asthma. On entry, the 73
      subjects had demonstrated more self-reported lifestyle restriction from asthma
      and more hospital admissions E.D. visits for asthma as well as poorer asthma
      control or than had the 305 subjects who had not required E.D. asthma treatment
      since entry to the cohort. This study suggests that special attention should be
      paid to subjects with asthma that interferes with their lifestyle and to those
      who have needed hospital admission for asthma.

PMID- 11321690
TI  - Healthcare online.

PMID- 11321691
TI  - Medical errors.

PMID- 11321692
TI  - Application service providers.

PMID- 11321693
TI  - Data security.

PMID- 11321694
TI  - XML.

PMID- 11321695
TI  - Supply chain management.

PMID- 11321696
TI  - Workflow automation.

PMID- 11321697
TI  - Wireless.

PMID- 11321698
TI  - Interactive technologies.

PMID- 11321699
TI  - Artificial intelligence.

PMID- 11321700
TI  - Convergence.

PMID- 11321701
TI  - Coping with a maturing industry.

PMID- 11321702
TI  - The bill drops here. Concurrent coding reduces billing delays, improves accuracy
      and saves time and money.
AB  - PROBLEM: Salinas Valley wanted to improve its reporting procedures to payors for
      reimbursement. Delays in reporting referred outpatients and inpatients can
      significantly impact receipt of reimbursements from payors. SOLUTION: Salinas
      Valley developed a program of concurrent coding in which every procedure is
      assigned a reimbursement code that is automatically registered in the patient's
      B/AR record when the procedure is logged into any of the clinical applications in
      the healthcare information system. RESULTS: Quicker turnaround on receiving
      payments from payors, as well as an increased return on investment as the ratio
      of reimbursement to cost-of-time-spent increases. KEYS TO SUCCESS: Integral to
      the success of the concurrent coding review program was the openness of the
      operating system at Salinas Valley.

PMID- 11321703
TI  - Digital doctoring.
AB  - PROBLEM: Clinicians and support staff struggled with the need to carefully track
      the clinical information flowing through the practice in a paper-based system,
      while at the same time providing the best possible patient care. SOLUTION: A
      browser-based software application automated the practice's complete workflow
      system--from scheduling and referrals management to lab and radiology results.
      RESULTS: Consolidated information and workflow management means everyone spends
      less time chasing paper and more time caring for patients. KEYS TO SUCCESS:
      Because today's information technology moves in a rapid sequence of incremental
      innovations, you can't wait for a "final" solution before you begin to automate.

PMID- 11321704
TI  - Evolution of telemedicine in the space program and earth applications.
AB  - Remote monitoring of crew, spacecraft, and environmental health has always been
      an integral part of the National Aeronautics and Space Administration's (NASA's)
      operations. Crew safety and mission success face a number of challenges in
      outerspace, including physiological adaptations to microgravity, radiation
      exposure, extreme temperatures and vacuum, and psychosocial reactions to space
      flight. The NASA effort to monitor and maintain crew health, system performance,
      and environmental integrity in space flight is a sophisticated and coordinated
      program of telemedicine combining cutting-edge engineering with medical
      expertise. As missions have increased in complexity, NASA telemedicine
      capabilities have grown apace, underlying its role in the field. At the same
      time, the terrestrial validation of telemedicine technologies to bring healthcare
      to remote locations provides feedback, improvement, and enhancement of the space
      program. As NASA progresses in its space exploration program, astronauts will
      join missions lasting months, even years, that take them millions of miles from
      home. These long-duration missions necessitate further technological
      breakthroughs in tele-operations and autonomous technology. Earth-based
      monitoring will no longer be real-time, requiring telemedicine capabilities to
      advance with future explorers as they travel deeper into space. The International
      Space Station will serve as a testbed for the telemedicine technologies to enable
      future missions as well as improve the quality of healthcare delivery on Earth.

PMID- 11321705
TI  - Pediatric tele-echocardiography: evaluation of transmission modalities.
AB  - Pediatric cardiology consultation has been effectively delivered outside the
      tertiary care setting through the use of tele-echocardiography. This study
      examined the effectiveness of several tele-echocardiography connections and the
      satisfaction of the referring physicians using these services. Studies were
      transmitted via either a shared fiber-optic (DS3) connection (two sites), a
      dedicated fast-copper (ISDN-PRI) link, or by courier from a nearby (25-mile) or
      distant (170-mile) site. Time intervals between when echocardiograms were
      performed locally until they were received, interpreted, and reported were
      prospectively recorded. Referring physician satisfaction was assessed through a
      survey. The critical time between when a remote echocardiogram was performed and
      when its result was reported to the referring physician was primarily determined
      by the mode of transmission. The time interval between performing an
      echocardiogram and receiving the study was significantly longer for
      echocardiograms sent from the 170-mile courier site (2474 +/- 295 min) than
      either the 25-mile courier site (474 +/- 151 min), DS3 (374 +/- 121 min), or ISDN
      PRI (129 +/- 16 min). Regardless of the method of transmission, all referring
      physicians felt that the service improved their ability to manage children, and
      they would recommend the service to their colleagues. Those using the courier
      service from the 25-mile away site were more concerned about the availability of
      a pediatric cardiologist and image quality, presumably due to the delay in
      response times. The time interval data provided in this study and the assessment
      of physician satisfaction provide important data as echocardiography laboratories
      implement tele-echocardiography services.

PMID- 11321706
TI  - Fluctuations in service loads in an established telemedicine program.
AB  - The goal of this investigation was to determine if there were identifiable
      patterns in the volume and types of teleconsults provided by an established
      telemedicine program over an extended period of time. Data from over 3 years of
      providing telemedicine consults within a university-based telemedicine programs
      were analyzed to identify trends and points of significant change in service
      provision. Teleconsult volume over a 40-month period was best fit by a
      logarithmic transformation of the regression curve that is characteristic of slow
      but steady growth. Consults have been provided in 53 subspecialties, with an
      average of 12 different subspecialties each month. Number of subspecialties per
      month was best fit by a sixth-order polynomial. Teleconsult volume has varied on
      a monthly basis, but overall volume has increased over time. This program has
      maintained its initial goal of being a multispecialty provider. Analyzing
      telemedicine consult data over extended periods of time is especially useful for
      long-term program evaluation and development of a successful business plan.

PMID- 11321707
TI  - Wireless ECG monitoring by telephone.
AB  - The objective of this work was to study a wireless one channel limited (3-lead)
      home electrocardiogram (ECG) transmission system and ambulatory devices data
      transmission using telephone lines. ECG screenings were conducted in two groups.
      The first group consisted of construction workers examined at first aid stations
      at construction sites in Moscow, Russia. The second group was a selected set of
      patients admitted to a hospital in Tblisi, Republic of Georgia. All patients were
      on constant monitoring and follow-up after hospitalization. Patients themselves
      connected the ECG leads at home or with the help of paramedics at ambulatory
      stations. The ECG signals were transmitted to receiving stations where doctors
      interpreted them. Frequency modulation was used for ECG transmission over regular
      telephone lines. Of 231 readings in 74 patients--70 male and 4 female (age 21-56)
      -in the first group, 33 patients were abnormal. In the second group, 15 out of
      165 readings in 8 patients--5 male and 3 female (age 31-70)--were abnormal. ECG
      screening can be significantly simplified and made widely acceptable at home and
      distant sites using wireless monitoring tools and telephone line transfer of the
      signal. This project has been implemented under the auspices of the International
      Telecommunication Union and the Russian Telemedicine Foundation.

PMID- 11321708
TI  - Suggested principles of professional ethics for the online provision of mental
      health services.
AB  - The goal of this project was to suggest principles of professional ethics for the
      online provision of clinical mental health services that could guide clinicians
      who provide and patients who receive such services. A joint committee of the
      International Society for Mental Health Online (ISMHO) and the Psychiatric
      Society for Informatics (PSI) was formed. Discussion and development of these
      principles took place online. A set of principles was produced and endorsed by
      ISMHO on January 9, 2000, and by PSI on May 13, 2000. The principles involve
      informed consent (about the process, the clinician, the potential risks and
      benefits, safeguards, and alternatives), standard operating procedure
      (competence, legal requirements, the structure of the services, evaluation,
      multiple treatment providers, confidentiality, records, and existing guidelines),
      and emergencies (procedures and local backup). This project demonstrates that
      traditional principles of professional ethics can be extended to online services,
      that comprehensive ethical principles can be developed by groups that cross
      disciplinary and national boundaries, and that productive collaboration can take
      place entirely online; and suggest that online clinicians have the potential to
      regulate themselves.

PMID- 11321709
TI  - Impact of varying transmission bandwidth on image quality.
AB  - The objective of this paper is to determine the effect of varying transmission
      bandwidth on image quality in laparoscopic surgery. Surgeons located in remote
      operating rooms connected through a telemedicine link must be able to transmit
      medical images for interaction. Image clarity and color fidelity are of critical
      importance in telementoring laparoscopic procedures. The clarity of laparoscopic
      images was measured by assessing visual acuity using a video image of a Snellen
      eye chart obtained with standard diameter laparoscopes (2, 5, and 10 mm). The
      clarity of the local image was then compared to that of remote images transmitted
      using various bandwidths and connection protocols [33.6 Kbps POTS (IP), 128 Kbps
      ISDN, 384 Kbps ISDN, 10 Mbps LAN (IP)]. The laparoscopes were subsequently used
      to view standard color placards. These color images were sent via similar
      transmission bandwidths and connection protocols. The local and remote images of
      the color placards were compared to determine the effect of the transmission
      protocols on color fidelity. Use of laparoscopes of different diameter does not
      significantly affect image clarity or color fidelity as long as the laparoscopes
      are positioned at their optimal working distance. Decreasing transmission
      bandwidth does not significantly affect image clarity or color fidelity when
      sufficient time is allowed for the algorithms to redraw the remote image. Remote
      telementoring of laparoscopic procedures is feasible. However, low bandwidth
      connections require slow and/or temporarily stopped camera movements for the
      quality of the remote video image to approximate that of the local video image.

PMID- 11321710
TI  - Utility of real-time video teleconferencing in conducting family mental health
      sessions: two case reports.
AB  - Due to the worldwide mission of the military, service members often find
      themselves isolated from their families and other important people in their
      lives. Historically, this has been especially problematic during periods of
      illness, as the isolation has precluded the meaningful involvement of families in
      patient care. With the increased availability of real-time video teleconferences
      (VTCs), however, providers may now gain access to family members. The Inpatient
      Psychiatry Department at Tripler has conducted therapeutic trials of family
      meetings using real time VTCs. These meetings are used to facilitate social
      support and mend family disconnections. The high clarity images offered through
      this system were instrumental in developing a virtual interactive social presence
      among the participants. Despite the potential benefits of VTC in gaining
      accessing to family support, there is little mention of such clinical family
      meetings in the medical literature. This report describes two case examples of
      the application of real-time family VTC in the management of mental illness.

PMID- 11321711
TI  - TERVA: system for long-term monitoring of wellness at home.
AB  - Long-term monitoring of physiological and psychosocial variables in out-hospital
      conditions would be beneficial for investigating changes in wellness status of an
      individual or to understand interaction between physiological and behavioral
      processes. We aimed to design a personal wellness monitoring system (TERVA),
      which would allow monitoring of wellness-related variables at home for several
      weeks or even months. The designed TERVA system runs on a laptop computer and
      interfaces with different measurement devices through a serial interface.
      Measured variables include beat-to-beat heart rate, motor activity, blood
      pressure, weight, body temperature, respiration, ballistocardiography, movements,
      and sleep stages. In addition, self-assessments of daily well-being and
      activities are stored by keeping a behavioral diary. To test the system, one
      healthy man used the system for 10 weeks. The system was successfully applied in
      out-hospital conditions. The success rate of the measurements was 70-91%,
      depending on the variable under consideration. The pilot study indicated that the
      recorded data accurately reflected the health status of the subject. The TERVA
      system provides a method to record and investigate wellness-related data over
      several weeks, or even months, outside the hospital among subjects capable of
      using a personal computer. Several applications of the system are discussed.

PMID- 11321712
TI  - Use of internet technologies for data acquisition in large clinical trials.
AB  - Data acquisition for automated processing is a central aspect of clinical trials
      with large numbers of cases because of their extensive demand for manpower.
      Scientific data can be collected using data forms, which are created in Hypertext
      Markup Language and published on the Internet. The completed data form can be
      returned via E-mail or Common Gateway Interface-Script and forwarded into a study
      database. For the Internet-based data acquisition of a prospective multicenter
      trial (e.g., on endophthalmitis incidence after cataract extraction), we
      developed two special HTML forms that can be opened in the ophthalmology
      department's homepage. A large number of acquired anonymous data has been
      collected via Internet and automatically transferred into the trial database. The
      Internet provides a fast and easy avenue for the acquisition of scientific data.
      This method of data acquisition and data processing will become more common place
      in multicenter clinical trials.

PMID- 11321713
TI  - Novartis to pigs: keep your kidneys.

PMID- 11321714
TI  - Validating phase relations between cardiac and breathing cycles during sleep.

PMID- 11321715
TI  - Heart rate variability and blood pressure analysis.

PMID- 11321716
TI  - The sympathetic nervous system's role in regulating blood pressure variability.

PMID- 11321717
TI  - Advancements in estimating baroreflex function.

PMID- 11321718
TI  - Closed- versus open-loop assessment of heart rate baroreflex.

PMID- 11321719
TI  - Comparing spectral and invasive estimates of baroreflex gain.

PMID- 11321720
TI  - Noninvasive estimation of baroreflex sensitivity using pressure pulse
      amplification.

PMID- 11321721
TI  - Applying nonlinear noise reduction in the analysis of heart rate variability.

PMID- 11321722
TI  - A mathematical model for autonomic control of heart rate variation.

PMID- 11321723
TI  - An optimal control model of 1/f fluctuations in heart rate variability.

PMID- 11321724
TI  - The complexity of heart rate in its postnatal development.

PMID- 11321725
TI  - Modeling of Mayer waves generation mechanisms.

PMID- 11321727
TI  - [Anatomy and pathology of intrahepatic and extrahepatic bile duct tumors].
AB  - Adenocarcinomas of the intra- and extrahepatic bile ducts are rare tumors that
      begin with malignant transformation of the bile duct epithelia. Intrahepatic
      cholangiocarcinomas derive from the small bile ducts located proximally to the
      right and left hepatic ducts. Extrahepatic bile duct carcinomas originate in the
      right or left hepatic duct, the cystic duct, or the choledochal duct. Tumors
      located at the bifurcation are called Klatskin tumors. The intrahepatic
      cholangiocarcinomas are classified according to the TNM classification of liver
      tumors, while the extrahepatic bile duct tumors have their own TNM
      classification. Several factors, accompanied by a chronic inflammatory reaction,
      have been discussed in the etiopathogenesis of these tumors: schistosomiasis,
      ulcerative colitis with primary sclerosing cholangitis, and inborn bile duct
      cysts of the liver as a consequence of a disturbance of the ductal plate
      formation. Over 95% of bile duct tumors are adenocarcinomas. In the nomenclature
      of precursor lesions a two-grade classification of dysplasia (low-grade versus
      high-grade) has been found to be more reproducible.

PMID- 11321726
TI  - [Gastroenteropancreatic neuroendocrine/endocrine tumors. Current pathologic
      diagnostic view].
AB  - Gastroenteropancreatic endocrine or neuroendocrine tumors (NETs) encompass a
      broad spectrum of neoplasms characterized by a heterogeneous biological behavior.
      They differ with regard to functional state, localization, and derivation from
      various segments of the primitive embryonal gut, growth pattern, degree of
      differentiation, expression of different neuroendocrine marker molecules, and
      prognosis. They occur generally as sporadic tumors but sometimes also in the
      setting of a familial cancer syndrome such as in type 1 multiple endocrine
      neoplasia or von Hippel-Lindau syndrome. The complex manifestations of NETs are
      reflected by the varying terms and classification systems. However, the terms
      "carcinoid" and islet cell tumor" do not indicate whether the tumors are benign,
      malignant, or of uncertain behavior. New clinical, morphological, and molecular
      developments in the field of neuroendocrine biology are contributing to the
      identification and characterization of NETs and are considered in the current
      World Health Organization classification.

PMID- 11321728
TI  - [Chronic hepatitis B virus and hepatitis C virus infections. Hidtology
      classification--examination].
AB  - Clinicians disagree over the need to perform liver biopsy in chronic infections
      with hepatitis B and C viruses, with opinions ranging from "useless" to
      "conditionally advisable" to "absolutely necessary." The frequency of liver
      biopsies has generally been declining, which entails decreased practical
      knowledge in the morphological examination of liver biopsies. As a result certain
      basic considerations must occasionally reemphasized.

PMID- 11321729
TI  - [Histological characteristics and prevalence of secondary osteoporosis in
      systemic mastocytosis. A retrospective analysis of 158 cases].
AB  - Mastocytosis is characterized by abnormal proliferation of mast cells especially
      within the skin and bone marrow and is often associated with osteoporosis. Mast
      cells can synthesize a variety of cytokines that are known to affect the skeletal
      system, but the cellular and pathophysiological mechanisms leading to
      osteoporosis in systemic mastocytosis remain poorly understood. To further
      characterize mastocytosis-associated osteoporosis we compared bone
      histomorphometric findings in iliac crest biopsy specimens from 158 untreated
      patients with mastocytosis. The overall prevalence of mastocytosis in the
      specimens diagnosed with osteoporosis was 1.25%, but that in patients younger
      than 45 years was 2.25%. The male-to-female ratio was 1:1, in contrast to 1:2 in
      osteoporosis. Osteopenia was present in 64% of the patients with mastocytosis,
      while osteosclerosis was rare (3%). Histological criteria are the concentric
      increase in mast cells in the perivascular tissue and the increase in elongated
      mast cells within the marrow space. Histomorphometry showed mastocytosis to be
      associated with moderate hyperosteoidosis and increased perforating bone
      resorption, indicated by a significant decrease in bone volume, trabecular
      thickness, and trabecular number as compared to controls. Osteoclast number was
      not altered, pointing to a functional effect of mast cells and/or its product on
      osteoclasts, rather than an effect on osteoclast differentiation. We conclude
      that although the prevalence of mastocytosis seems to be low, its correct and
      early diagnosis is crucial for at least 2.25% of younger patients with
      osteoporosis.

PMID- 11321730
TI  - [Sudden cardiac death from unrecognized cardiac sarcoidosis].
AB  - Sarcoidosis is a systemic disease of young adults. Cardiac involvement is rarely
      diagnosed clinically. It presents with arrhythmias, conduction disorders,
      increasing myocardial insufficiency, or sudden death. We report a 42-year-old man
      with cardiac conduction disturbances of unknown cause who died of sudden cardiac
      death. Sarcoidosis with prominent cardiac involvement was diagnosed only at
      autopsy. Cardiac sarcoidosis should be considered in young patients with
      unexplained conduction disorders.

PMID- 11321731
TI  - [Endometrial metastasis of a "balloon" cell melanoma mimicking a "xanthomatous
      endometritis"].
AB  - Xanthomatous changes are unusual lesions of the corpus endometrium that may mask
      endometrial carcinoma. The term "xanthomatous endometritis" refers to
      morphological changes frequently induced by estrogen stimulation. We report for
      the first time a case of uterine metastasis of balloon-cell melanoma mimicking
      xanthomatous endometritis. Light microscopic, immunohistological, and
      ultrastructural results are presented and discussed in connection with our ideas
      on the pathogenesis of this peculiar tumor. The findings favor the hypothesis of
      a regressive phenomenon in the balloon-cell transformation of melanoma cells. The
      melan-A immunohistology seems to be more important in the diagnosis of balloon
      cell melanoma than the classic melanoma antibody HMB 45.

PMID- 11321732
TI  - [Congenital pulmonary fibrosarcoma. Differential diagnosis of infantile pulmonary
      spindle cell tumors].
AB  - Primary pulmonary mesenchymal tumors are rare causes of intrathoracic lesions in
      newborns. We describe a case of pulmonary spindle-cell tumor with features of
      infantile fibrosarcoma and discuss the differential diagnosis of spindle-cell
      lesions in this location. In view of further case reports of the literature, this
      neoplasia can best be categorized in a spectrum of fibroblastic/myofibroblastic
      differentiated spindle-cell tumors, with excellent prognosis. Especially in
      congenital lesions a favorable clinical course is to be expected after complete
      surgical resection. Additional radio- and/or chemotherapy is not recommended.

PMID- 11321733
TI  - [Acral myxoinflammatory fibroblastic sarcoma. Six cases of a tumor entity].
AB  - Acral myxoinflammatory fibroblastic sarcomas are low-grade sarcomas of the distal
      extremities, first described by Meis-Kindblom and Kindblom in 1998. In our series
      of six cases this sarcoma occurred in four men and two women aged 22-60 years
      (mean 42.8). The tumors measured 1-4 cm (mean 2.4) and were localized in the foot
      (two cases), finger (two), wrist (one), and upper arm (one). The patients had a
      short history of a painless mass (mean duration 3 months). The tumors were poorly
      circumscribed, and infiltrated the subcutaneous fat and in one case each also the
      dermis and musculature. Histological features of the tumors were a multinodular
      configuration with infiltrative margins, myxoid and fibrotic zones with
      hyalinized areas, moderately pleomorphic cells with large cells showing a
      prominent nucleolus and an inflammatory infiltrate consisting of lymphocytes and
      histiocytes. Two months after excision the tumor recurred locally in two cases;
      no metastases were observed. Differential diagnosis is especially necessary from
      inflammatory pseudotumors and more aggressive sarcomas.

PMID- 11321734
TI  - [Histology of Crohn disease type lesions in the upper gastrointestinal tract].
AB  - Most patients with Crohn's disease undergo upper endoscopy with biopsy at least
      once, and for the pathologist it is of utmost importance to classify the lesions
      observed in biopsy specimens from the upper gastrointestinal tract. Duodenal and
      gastric specimens present two patterns of inflammation: a focal inflammation,
      with the inflammatory process restricted to a few glands, and a discontinuous
      inflammation, with the inflammation involving the entire or at least large parts
      of the specimens. In the latter, the mucosal architecture is compromised. The
      occurrence of epitheloid granulomas may support the diagnosis of Crohn's disease,
      but is not mandatory. Crohn's disease can be recognized in specimens taken from
      the esophagus only if granulomas or giant cells are found beneath the epithelial
      layer. This review discusses the most important differential diagnoses of
      inflammatory lesions in the upper gastrointestinal tract.

PMID- 11321735
TI  - [Gastric differentiated stomach adenocarcinoma].
AB  - Gastric carcinomas are classified histogenetically into diffuse and
      differentiated types. The latter are often referred to as intestinal-type
      carcinomas and are believed to originate from intestinal metaplasia. However,
      histogenetic studies on smaller and initial lesions of the differentiated
      adenocarcinoma do not support this. From phenotypical expressions of neoplastic
      lesions arising in hyperplastic polyps of the stomach we first proposed an entity
      of gastric-type adenocarcinomas, which has been widely accepted. Our recent mucin
      and immunohistochemical investigations reveal that most smaller adenocarcinomas
      retain gastric-type differentiation and that those of the exclusively intestinal
      phenotype are rather rare. On the other hand, most adenomas are strongly and
      extensively positive for intestinal marker, indicating that the adenoma-carcinoma
      sequence is not a common event in the stomach carcinogenesis. Other studies show
      that the expression of intestinal mucin or carbohydrate antigen as expressed in
      intestinal metaplasia is manifested more extensively in carcinoma cells in larger
      tumors. It is suggested that intestinalization of tumor cells is a time-dependent
      phenomenon. Differential gene abnormalities between gastric- and intestinal-type
      carcinomas of the stomach are discussed, regarding their histogenesis and
      progression.

PMID- 11321736
TI  - The role of MR imaging for the assessment of complicated duplex kidneys in
      children: preliminary report.
AB  - OBJECTIVE: To determine whether MR imaging, including MR urography, is able to
      assess complicated duplex kidneys and to determine the possible role of MRI
      compared to other imaging techniques in such uropathies. MATERIAL AND METHODS:
      Twenty consecutive patients (age 1 month-11 years) presenting with a suspicion of
      a complicated duplex kidney were prospectively studied with MRI and MR urography.
      The examinations were performed on a 0.5-T machine using routinely available
      sequences that were optimised to the patient's age and size. MR images were
      reviewed separately by two observers blinded to the patient history. They were
      asked to assess the presence of a duplex kidney, the presence of an abnormality
      that may require surgery and to indicate the type of the inferior ureteric
      insertion. A qualitative gradation of these results was performed on the basis of
      the final diagnosis provided at endoscopy (n = 6) or surgery (n = 14). MR results
      were compared to those provided by US examinations and excretory urography, when
      available, and a non-parametric statistical analysis was performed. RESULTS: MRI
      differentiated well between the upper and the lower poles of the kidneys and
      correctly answered the three questions in all 20 patients. The two observers
      agreed completely in all the 20 patients. MR was statistically superior to both
      US and excretory urography in the evaluation of the distal ureter (P < 0.05).
      CONCLUSIONS: MRI provides a precise assessment of the complications associated
      with duplex kidneys. Its optimal role seems to be the assessment of ectopic extra
      vesical ureteric insertions and whenever an occult upper pole is suspected.

PMID- 11321737
TI  - Ureteric prolapse in a child.

PMID- 11321738
TI  - Congenital absence of the nose: a case report and literature review.
AB  - A case of congenital absence of the nose is presented. The etiology of this rare
      condition is unknown. A review of the literature reveals that the previously
      applied terms, e.g. 'arhinia', are unclear. In the reviewed cases there seems to
      be a pattern of facial anomalies associated with nasal absence. In most cases,
      one could probably expect a lack of the olfactory bulbs and tracts. We suggest a
      new terminology and summarize the aims of the radiological evaluation of this
      condition.

PMID- 11321739
TI  - Rhabdoid tumour of the kidney: imaging findings.
AB  - BACKGROUND: Rhabdoid tumour of the kidney (RTK) is a rare tumour, but it is the
      most aggressive malignant neoplasm of the kidney in children. OBJECTIVE: To
      analyse the radiological findings of RTK in children. MATERIALS AND METHODS: The
      clinical and radiological findings in seven children (age range 6 months to 4.7
      years; median 18 months) with pathologically proven RTK were retrospectively
      reviewed. We analysed tumour size, tumour location, tumour margin, subcapsular
      haematoma, tumour necrosis, haemorrhage, calcification and lymphadenopathy.
      RESULTS: Tumour size varied from 5 to 12 cm. Four tumours were located mainly in
      the central portion of the kidney, while three tumours were mainly sited
      peripherally. The margins of the tumour were ill-defined in four (57%) of seven
      cases, a lobulated tumour surface was depicted in all seven (100%), subcapsular
      haematoma was present in four (57%), tumour necrosis or haemorrhage in seven
      (100%), calcifications in three (43%) and retroperitoneal lymphadenopathy in four
      (57%). CONCLUSIONS: Imaging findings of RTK are subcapsular haematoma, a
      lobulated surface of the tumour, calcification and tumour necrosis or
      haemorrhage.

PMID- 11321740
TI  - Paediatric fluoroscopy--a survey of children's hospitals in Europe. I. Staffing,
      frequency of fluoroscopic procedures and investigation technique.
AB  - BACKGROUND: Fluoroscopy is an important, sometimes vital radiological procedure
      in paediatric patients with high variability in frequency and technique.
      OBJECTIVE: To obtain data on paediatric fluoroscopy practice in Europe using a
      simple questionnaire mailed to 191 children's hospitals. RESULTS: Eighty-eight
      radiology departments in 21 European countries participated in the survey. There
      was great variation in the size of paediatric hospitals in Europe and,
      consequently, the numbers of staff members (radiographers and radiologists). The
      total number of fluoroscopy procedures varied widely; the mean value was 1,073
      examinations per year. The most frequent fluoroscopic examination was the
      micturating cystourethrogram, comprising 40% of total fluoroscopies. For all
      types of investigations there were enormous differences in the number of spot
      film images routinely obtained. Only a few departments have prepared protocols
      for junior doctors or radiographers. CONCLUSIONS: Although the number of
      fluoroscopic investigations per radiologist does not reflect real workload (the
      difficulty of the investigation was not requested), it can be stated that a
      considerable percentage of children's hospitals are understaffed. These results
      also clearly demonstrate that fluoroscopy guidelines for the most common
      investigations in paediatric patients are needed to improve the quality of
      examinations and limit radiation exposure to the patients.

PMID- 11321741
TI  - MRI-compatible audio/visual system: impact on pediatric sedation.
AB  - BACKGROUND: While sedation is necessary for much pediatric imaging, there are new
      alternatives that may help patients hold still without medication. OBJECTIVE: We
      examined the effect of an audio/visual system consisting of video goggles and
      earphones on the need for sedation during magnetic resonance imaging (MRI).
      MATERIALS AND METHODS: All MRI examinations from May 1999 to October 1999
      performed after installation of the MRVision 2000 (Resonance Technology, Inc.)
      were compared to the same 6-month period in 1998. Imaging and sedation protocols
      remained constant. Data collected included: patient age, type of examination, use
      of intravenous contrast enhancement, and need for sedation. The average supply
      charge and nursing cost per sedated patient were calculated. RESULTS: The 955
      patients from 1998 and 1,112 patients from 1999 were similar in demographics and
      examination distribution. There was an overall reduction in the percent of
      patients requiring sedation in the group using the video goggle system from 49 to
      40% (P < 0.001). There was no significant change for 0-2 years (P = 0.805), but
      there was a reduction from 53 to 40% for age 3-10 years (P < 0.001) and 16 to 8%
      for those older than 10 years (P < 0.001). There was a 17% decrease in MRI room
      time for those patients whose examinations could be performed without sedation.
      Sedation costs per patient were $80 for nursing and $29 for supplies. CONCLUSION:
      The use of this video system reduced the number of children requiring sedation
      for MRI examination by 18%. In addition to reducing patient risk, this can
      potentially reduce cost.

PMID- 11321742
TI  - Thallium bone imaging as an indicator of response and outcome in nonmetastatic
      primary extremity osteosarcoma.
AB  - PURPOSE: We investigated one 201Tl bone scintigraphy method as a predictor of
      histologic response and event-free survival (EFS) of nonmetastatic extremity
      osteosarcoma. MATERIALS AND METHODS: We evaluated images of the primary tumor to
      determine whether they exhibited a donut of avidity for 40 patients enrolled on a
      single institutional protocol. Participants underwent three serial 201Tl bone
      scintigraphy studies during preoperative neoadjuvant chemotherapy. Intra- and
      interobserver variability of the method was assessed, and the presence of the
      donut of avidity was examined as a predictor of EFS and histologic response.
      RESULTS: Fifty-three percent of patients were female and 75% were Caucasian; the
      median age at diagnosis was 13.5 years. Intraobserver agreement was moderate to
      very good, ranging from 0.595 to 0.865. Interobserver agreement was moderate to
      good for all time points, ranging from 0.576 to 0.708. There was a significant
      difference in EFS among patients with and without the donut-shape at any of the
      three time points (P = 0.049); patients whose tumors displayed a donutshape had
      inferior EFS. CONCLUSION: The pattern of donut avidity in extremity OS is a
      predictor of lower EFS, but does not correlate with histologic response to
      therapy.

PMID- 11321743
TI  - Sickle cell disease with orbital infarction and epidural hematoma.
AB  - Although bone infarction is a common feature in sickle cell disease, the
      involvement of the orbit is an unusual complication. Intracranial bleeding is
      another uncommon and serious complication. Few cases of orbital infarction alone
      have been reported. We report imaging findings (CT, bone scan, MRI) in a 16-year
      old boy with sickle cell disease with orbital infarction and epidural hematoma.
      The precise cause of epidural hematoma is not well known, but it is probably
      related to vaso-occlusive episodes and the tearing of small vessels.

PMID- 11321744
TI  - Pitfalls in the sonographic diagnosis of juxtadiaphragmatic pulmonary
      sequestrations.
AB  - BACKGROUND: Sonographic evaluation of juxtadiaphragmatic lesions is frequently
      the initial imaging modality of choice in the pediatric population. The
      increasing sophistication of sonographic and Doppler technologies has led to the
      suggestion in the literature that lesions suspected of being juxtadiaphragmatic
      pulmonary sequestrations can be confidently imaged by ultrasound examination
      alone. OBJECTIVE: To present four cases which raise concern over the accuracy of
      sonographic examination of these lesions. MATERIALS AND METHODS: We present four
      such lesions for which an initial erroneous diagnosis of pulmonary sequestration
      was suggested on an initial ultrasound examination. CONCLUSION: The potential of
      a missed diagnosis of neuroblastoma has led us to propose that any lesion not
      demonstrating unequivocal sonographic findings of pulmonary sequestration should
      undergo further investigation and, if necessary, tissue sampling or excision.

PMID- 11321745
TI  - Complex bronchopulmonary foregut malformation: extralobar pulmonary sequestration
      associated with a duplication cyst of mixed bronchogenic and oesophageal type.
AB  - We report a 13-year-old girl with an unusual, complex bronchopulmonary foregut
      malformation. The malformation included extralobar pulmonary sequestration and a
      duplication cyst of mixed bronchogenic and oesophageal type. Preoperative CT and
      MRI demonstrated the cystic and solid portions of the mass and indicated an
      aberrant vascular supply, suggesting the possibility of bronchopulmonary foregut
      malformation and several other differential diagnoses. A direct communication
      between the cyst and the bronchus of the sequestrated lung was found on
      pathological examination. This unusual combination of an extralobar pulmonary
      sequestration and a foregut cyst points to a common embryological pathogenesis.

PMID- 11321746
TI  - Use of imaging for assessing anatomical relationships of tracheobronchial
      anomalies associated with left pulmonary artery sling.
AB  - BACKGROUND: Proper recognition, classification and assessment of the
      tracheobronchial anatomy are essential for surgical management planning in left
      pulmonary artery sling (LPAS). OBJECTIVE: To demonstrate the various imaging
      modalities in diagnosing and assessing anatomical relationships with
      tracheobronchial tree in LPAS. MATERIALS AND METHODS: Seven patients (three
      infants, three children, one adult) with LPAS were evaluated. The confirmative
      imaging modalities included electron-beam tomography (EBT, n = 2), MRI (n = 1)
      and helical CT (n = 4). Other imaging modalities included plain chest radiographs
      (n = 7), barium oesophagogram (n = 2), echocardiography (n = 3), cardiac and
      pulmonary angiography (n = 2) and bronchoscopy (n = 5). RESULTS: There were two
      cases of type IA, one case of type IIA and four cases of type IIB. All five cases
      of type II had a long segment of tracheobronchial stenosis. A long segment of
      thoracic tracheal stenosis was unusually associated in one case of type IA. All
      confirmative modalities were sufficient for diagnosing LPAS and assessing the
      tracheobronchial tree anomaly. However, helical CT could not obviate angiography
      due to associated congenital cardiac defects. CONCLUSIONS: Sectional imaging
      modalities of EBT, MRI and helical CT were all sufficient for diagnosing and
      assessing the anatomical relationships of the tracheobronchial tree in LPAS.

PMID- 11321747
TI  - Patent ductus venosus: diagnosis by MR angiography.
AB  - We report a 15-year-old boy with patent ductus venosus in whom the diagnosis was
      made by MR angiography. A patent ductus venosus Arantii is a rare form of
      portosystemic shunt. Only a few cases have been reported in adults and children.
      The diagnosis is usually made by US and digital subtraction angiography. In our
      patient, the diagnosis was first made by MR angiography. This demonstrates the
      excellent diagnostic potential of the method in paediatric patients.

PMID- 11321748
TI  - 99mTc-sulphur-colloid and heat-denatured 99mTc-labelled red cell scans
      demonstrating a giant intrapelvic spleen in a girl after splenectomy.
AB  - A 17 x 12 x 5-cm giant intrapelvic mass in a 14-year-old girl is reported. This
      mass developed 6 years after a splenectomy for splenic torsion. The heat
      denatured 99mTc-labelled red cell scan and 99mTc-sulphur-colloid scan confirmed
      the specific red cell sequestration function and reticuloendothelial activity in
      the giant intrapelvic spleen. The size and development of the giant intrapelvic
      spleen are unusual. The usefulness of functional images to diagnosis the nature
      of the intrapelvic mass is well demonstrated.

PMID- 11321749
TI  - Dorsolumbosacral agenesis.
AB  - Caudal regression is a rare congenital spinal anomaly characterized by partial or
      total agenesis of the sacral and/or lumbar spine. Sacral and/or lumbosacral
      agenesis has been well described. However, especially as far as MRI studies are
      concerned, thoracolumbosacral agenesis has rarely been reported.

PMID- 11321750
TI  - Ellis-van Creveld syndrome: a generalized dysplasia of enchondral ossification.
AB  - We report a 25-week fetus with lethal Ellis-van Creveld syndrome who was
      diagnosed prenatally from the US detection of a narrow chest, postaxial
      polydactyly of the hands, short acro-/mesomelic limbs and a ventricular septal
      defect. The postnatal radiographic features of the skeleton confirmed the
      diagnosis. Literature review of the histopathology of the physeal growth plate is
      contradictory, varying between retardation of the hypertrophic chondrocytes
      without disorganization and marked disorganization of the proliferating
      chondrocytes. We investigated numerous sites of the enchondral ossification and
      observed retardation of the physeal growth plate in all sites and retardation
      with pronounced disorganization of the physeal growth plate in the upper
      mesomelic bone segments only. These data support the concept that Ellis-van
      Creveld syndrome is mainly a generalized disorder of the maturation of enchondral
      ossification.

PMID- 11321751
TI  - Calcified subcutaneous fat necrosis induced by prolonged exposure to cold
      weather: a case report.
AB  - We present a 22-day-old infant with extensive subcutaneous calcifications due to
      subcutaneous fat necrosis caused by prolonged exposure to cold.

PMID- 11321752
TI  - Sonographic appearances of the abdominal manifestations of hereditary angioedema.
AB  - Hereditary angioedema (HAE) is the autosomal dominant deficiency of C1-esterase
      inhibitor. There have hitherto been no reports on the US appearances of HAE. The
      unique case of a 12-year-old girl with recurrent abdominal pain is reported, in
      whom HAE was diagnosed by US and family history of paroxysmal dyspnoea, cutaneous
      swelling and attacks of abdominal pain. Pertinent US features were intestinal
      oedema and ascites. Sonographic evidence of intestinal swelling was only seen on
      the initial day of an episode of abdominal pain. Oedema, as demonstrated by MRI
      the following day, regressed rapidly, whereas ascites persisted for at least 3
      days. It is therefore important to perform imaging in the acute phase to
      demonstrate the massive intestinal oedema, which is characteristic for the
      disease.

PMID- 11321753
TI  - Radiographic resolution of lymphocytic interstitial pneumonitis (LIP) in children
      with human immunodeficiency virus (HIV): not a sign of clinical deterioration.
AB  - BACKGROUND: The literature and anecdotal evidence associate the resolution of
      radiographic findings of lymphocytic interstitial pneumonitis (LIP) with a
      decline in immune and clinical status of human immunodeficiency virus (HIV)
      infected children. OBJECTIVE: As our clinical impression was the opposite, we
      sought to elucidate this contradiction. MATERIALS AND METHODS: Of 52 pediatric
      patients infected with the HIV currently being followed at our institution, 20
      (38.5%) carried the diagnosis of LIP and 13 (65%) of these have had complete
      resolution of radiographic findings of LIP. We retrospectively reviewed the chest
      radiographs, CD4 counts, and clinical history of these 13 patients. RESULTS: Of
      the 13 patients who had resolution of radiographic findings, 11 (84.6%) had no
      significant change in CD4 count at the time of resolution and remained clinically
      stable during a mean follow-up period of 32 months. Two patients (15.3%)
      developed severe CD4 lymphocytopenia at the time of resolution of LIP, but
      clinically remained stable. None of these 13 patients had a recurrence of LIP,
      even with subsequent increases in CD4 count. CONCLUSION: We suggest that in
      contradiction to previously published data, resolution of LIP on chest
      radiographs is not an indicator for poor prognosis for the HIV-infected pediatric
      patient.

PMID- 11321754
TI  - Giant retroperitoneal lipoma in a child.

PMID- 11321755
TI  - Apparent suprarenal mass: splenic cleft and persistent lobules.

PMID- 11321756
TI  - Hepatoblastoma.

PMID- 11321757
TI  - Single-use device reprocessing companies. How to choose.
AB  - Now that the U.S. Food and Drug Administration (FDA) has come out with its final
      policy on reusing single-use medical devices (SUDs), many hospitals are reviewing
      their options concerning reuse. Because FDA's policy imposes a whole new set of
      burdens on U.S. facilities that reprocess SUDs, a number of those hospitals will
      undoubtedly decide that they don't want to support an in-house reprocessing
      program anymore. Some hospitals will turn to third-party reprocessing companies
      to take on this burden for them. But choosing a reprocessor isn't as simple as
      looking up a name in the phone book. It's vital that a reprocessor be able to
      handle the devices that the hospital wants to reprocess (not all companies
      reprocess all devices). It's also vital that the company have policies and
      procedures in place that will allow it to provide dependable, high-quality
      service. And it's vital that the hospital be comfortable with the company or
      companies that it chooses. This article outlines the issues you need to examine
      when choosing a third-party reprocessing company. It also includes a checklist
      that you can use to judge each company under consideration.

PMID- 11321758
TI  - Stationary surgical smoke evacuation systems.
AB  - Two types of systems are available for evacuating the surgical smoke created by
      electrosurgery and laser surgery: portable and stationary surgical smoke
      evacuation systems. While portable systems dominate the market today, stationary
      systems are an alternative worth considering--even though they are still in their
      infancy, with fewer than 90 systems installed to date. Stationary systems
      represent a major commitment on the part of the healthcare facility. Several
      system components must be installed as part of the physical plant (for instance,
      within the walls), making the system a permanent fixture in the surgical suite.
      Installation of these systems is often carried out during building construction
      or major renovation--although the systems can be cost-effective even if no
      renovations are planned. For this Evaluation, we tested three stationary systems.
      All three are adequate to capture surgical smoke and evacuate it from the
      operating room. These systems are easy to use, are quietter than their portable
      counterparts, and require minimal user maintenance. They represent an excellent
      option for most hospitals actively evacuating surgical smoke. In this article, we
      discuss the factors to consider when selecting from among these systems. We also
      offer guidance on choosing between stationary systems and portable ones.

PMID- 11321759
TI  - Medical gas safety. Read the labels! They're the only sure identifier of gas
      cylinder contents.
AB  - Mixing up different types of medical and device gases can have damaging and even
      deadly consequences. Therefore, it's vital that hospital staff members understand
      that only the label on a gas cylinder is a reliable indicator of its contents.
      Any other indicators--such as the type of connector on the cylinder, or the color
      the cylinder is painted--could be misleading, since the standards covering these
      indicators sometimes overlap and may be poorly understood. This article discusses
      how and why the wrong indicators might lead an unsuspecting staff member to use
      an inappropriate type of gas, and how hospitals can minimize the odds of this
      happening.

PMID- 11321760
TI  - Misloading of the Abbott Acclaim Encore infusion pump can lead to fluid
      underdelivery.

PMID- 11321762
TI  - Deposits may form in humidifier of Hill-Rom Air-Shields C2HS isolette infant
      incubators.

PMID- 11321761
TI  - Using the Disetronic H-TRONplus V100 insulin pump in water can result in
      overinfusion.

PMID- 11321763
TI  - [New trends in surgery].

PMID- 11321764
TI  - [Nurturing young surgeons in a competitive society].
AB  - Creating and maintaining harmony between natural science and social science is
      very important for the establishment of a truly rich society in the 21st century.
      Young surgeons must acquire deep knowledge and excellent techniques, in addition
      to contributing to social development and human happiness. This paper outlines my
      personal views of what young surgeons need to do to succeed at all levels in the
      current competitive society.

PMID- 11321765
TI  - [The goals of the Japanese Surgical Society should not be merely for specialized
      surgery: they should be for general surgery, surgical education and better
      medical legislation].
AB  - The Japan Surgical Society (JSS) should investigate mainly general surgery,
      surgical education, and political approach. The Specialized surgery, which has
      also been studied by the JSS, should be fully evaluated in various subspecialty
      surgical societies, i.e. gastrointestinal, respiratory, circulatory, pediatric,
      and others. This is reasonable, since the board of each subspecialty has the same
      basic requirements as the board of the JSS and this is how the JSS and other
      surgical subspecialty societies can coexist. In addition, the JSS must make
      efforts to improve surgeons' lives overall by means of effective politics and to
      motivate medical students to become surgeons to prevent a scarcity, which will
      also contribute to the welfare of the public.

PMID- 11321766
TI  - [Surgery and the Japan Surgical Society at the beginning of the 21st century].
AB  - Numerous advances in medicine occurred during the latter half of the 20th
      century, and progress will accelerate in the 21st century. In particular,
      research in molecular biology has made significant advances, and it was reported
      that the human genome was almost completely deciphered in June 2000. This will
      contribute greatly to genetic research in malignant diseases. The development of
      regenerative medicine, such as cell transplantation using differentiated
      embryonic or mesenchymal stem cell, will have a significant effect on the field
      of surgery. The Japan Surgical Society must apply the new knowledge being made
      available to realize the concept of integrative medicine, in which surgery will
      play a major role. Substantial changes in postgraduate and continuing education
      and training of surgeons may be necessary. Other topics for discussion include
      risk management in the case of surgical accidents and medical ethics based on the
      Declaration of Helsinki.

PMID- 11321767
TI  - [Surgery in the age of the individual].
AB  - Surgical medicine has developed with contribution from the basic medical
      sciences. At the same time, the life sciences have developed rapidly and are
      being applied clinically. Thus, the 20th century was the "age of science," and
      the age when science was valued the most. What is necessary in the 21st century?
      The further development of surgery is anticipated. In addition, since it is
      believed that the 21st century will be the "age of the individual". I think that
      surgical medicine should address human individuality. In the 21st century, the
      Japan Surgical Society should promote surgical medicine by adhering to the dictum
      of Ambroise Pare: "to cure sometimes, to relieve often, to comfort always."

PMID- 11321768
TI  - [Developing the best and the brightest in academic surgery for next generation].
AB  - Major advances have been achieved in surgery during the past century and further
      dynamic changes are expected along with progress in immunology, tissue and
      mechanical engineering, etc. in the 21st century. However, fewer medical students
      will choose the surgical field as their specialty, primarily due to the long
      training period, and inadequate income as compared to the heavy workload. To
      recruit the best and the brightest students in surgery, early exposure to the
      positive aspects of the surgical field is desirable. The training system should
      be further refined, and a sufficient number of positions with appropriate
      remuneration must be mode available.

PMID- 11321769
TI  - [Characterization of a highly proliferative population of adult hepatocytes and
      its use for tissue engineering].
AB  - It is well known among cell biologists that normal hepatocytes of adult mammals
      are difficult to replicate repeatedly in vitro, irrespective of the fact that
      these cells can grow well clonally in vivo. We developed a culture medium (HCGM)
      wherein the normal hepatocytes of adult Fischer rats replicate repeatedly and
      form clonal colonies. This growth requires the presence of hepatic stellate cells
      (HSCs). Fractionation and separation of hepatocytes by a combination of
      centrifugation and cell sorting revealed the presence of a highly proliferative
      population of hepatocytes in the adult liver, called small-sized hepatocytes (SHs
      R3). SHs-R3 showed a 3- to 4-fold higher growth potential than large-sized
      hepatocytes (SHs-R2) both in vitro and in vivo. The in vivo growth potential was
      estimated using the retrorsine-dipeptidylpeptidase IV (DPPIV)--rat model in which
      DPPIV-positive SHs-R3 were transplanted into the liver of retrorsine-treated
      DPPIV-negative mutant rats which were then subjected to two-thirds partial
      hepatectomy. The results of our studies suggest a close relationship between SHs
      R3 and small hepatocyte-like progenitor cells, as reported by Gordon et al. We
      showed that the liver of adult humans also contains a highly proliferative
      population of hepatocytes, which possibly corresponds to SHs-R3. Research is now
      being undertaken to utilize this population of human hepatocytes to develop an
      artificial liver.

PMID- 11321770
TI  - [Perspectives on regenerative therapy].
AB  - Organ transplantation and artificial organs are the only effective treatments for
      loss of organ and tissue function. These treatments, however, are associated with
      serious problems such as a critical shortage of donor organs, rejection, the need
      for life-long immunosuppression, and unstable biocompatibility. These
      shortcomings have stimulated the development of tissue engineering. Tissue
      engineering is defined as an interdisciplinary field that applies the principles
      of engineering and the life sciences to the development of biological substitutes
      that restore, retain, or improve tissue function. Tissue engineering is composed
      of three factors: cells; growth factors; and scaffolds. Regenerative medicine
      includes two important fields: tissue engineering; and regenerative biology.
      Regenerative therapy is a newly developed medical therapy based on the research
      results of regenerative medicine. The fields of regenerative therapy includes
      broad areas of basic and clinical sciences, bioethics, and medical economics in
      addition to the area of regenerative medicine. Cell sources and cell expansion
      are important issues in regenerative medicine. Great efforts are being made to
      isolate and identify the characteristics of stem cell populations of various
      tissues. The use of stem cells may provide an almost limitless supply of cells
      for transplantation. Although there are still many important issues to be
      resolved, regenerative medicine has been making rapid progress using a
      multidisciplinary approach. The success of this approach will lead to the
      widespread application of regenerative therapy and may ultimately be able to
      replace lost tissue function in the 21st century. We should, however, keep in
      mind the importance of bioethics in using any new therapy.

PMID- 11321771
TI  - [Training in specialties and subspecialties of surgery: current system in Japan
      and a proposal for the future].
AB  - The maintenance of quality care of surgical patients is the primary concern of
      surgeons. The Japan Surgical Society has taken the responsibility for
      establishing standards for the quality care of patients in surgery and surgical
      subspecialties. The society introduced training systems for surgeons and
      developed qualifying examinations after 4 years of training in general surgery in
      1984, but after 24 years, in response to the demands from surgeons and patients,
      new training, certification, and recertification programs are under investigation
      by the Japan Surgical Society and its related societies of subspecialties.
      Currently, a 3-year training system and subsequent qualifying examination for
      gastroenterological surgery, pediatric surgery, cardiovascular surgery and
      pulmonary surgery are being proposed after completing 4-year training and
      qualifying examination in general surgery. The pros and cons of this system are
      discussed and a more desirable system for the future is proposed.

PMID- 11321772
TI  - [Future figures of specialties in the surgical field].
AB  - A quarter of century has passed since specialties and their governing boards were
      established in the surgical field. It is now time to reestablish more definitive
      and rational specialties as we begin the 21st century. The specialty of general
      surgery should be the first step and require general surgical training of four
      years or more. The subsequent specialties (subspecialties) would be
      gastroenterological surgery, cardiovascular surgery, respiratory organ surgery,
      and pediatric surgery. In addition, the numerous medical associations in Japan
      could be overseen by a newly created Japan Board of Medical Specialties (proposed
      name) to manage the various specialties.

PMID- 11321773
TI  - [To err is human but error can be prevented].
AB  - It is believed that behind each reported medical error 29 unreported errors are
      hidden and in addition 300 irregularities are present. To prevent medical errors,
      one should learn from those latent errors to reorganize or correct systems and
      procedures. The Risk Management Committee is in charge of taking measures to
      prevent errors based on the analyzed data reported by risk managers and/or on
      incident/accident reports. The incident/accident reports should be made under a
      blame-free system and the concept should be thoroughly understood by all hospital
      staff. A lack of mutual communication, lack of a system to prevent medical
      errors, and lack of seriousness in everyday practice among physicians and nurses
      were found to be underlying causal factors in medical errors based on the lessons
      learned in our institution.

PMID- 11321774
TI  - [Legal settlements of medical accidents].
AB  - When an accident occurs during the course of clinical treatment, it is important
      to record the series of events as objectively as and in the most precise detail
      possible. The causes of the accident should be investigated with all due speed,
      and an accurate, consistent account should be rendered to the patient's family.
      When the cause of a patient's death is not clear, a pathological autopsy should
      be performed. It is the legal responsibility of physicians to notify the police
      of unexpected death when medical malpractice is suspected, and in compliance with
      the law an autopsy must be performed. A malpractice suit brought against a
      medical institution can be settled by two means: out-of-court settlement; and
      court decision. An out-of-court settlement in the event of obvious medical error
      is the more desirable option from the viewpoint of immediate relief of patients
      and/or ther families. At present, an average of three years elapses before a
      medical malpractice suit can be resolved in the courts. One of the main reasons
      for this delay in the settlement of court case is the difficulty in obtaining
      competent expert witnesses, and therefore members of the Japan Surgical Society
      should cooperate actively with the legal authorities in medical malpractice
      suits.

PMID- 11321775
TI  - [Long-term observations on type distribution of clinical isolated of beta
      hemolytic streptococci in Sapporo. I. T-type distribution of group A hemolytic
      streptococci during the thirty one-year period between 1969 and 1999].
AB  - During the thirty one-year period between 1969 and 1999, a total of 6,876 strains
      of group A streptococci isolated in Sapporo City General Hospital were classified
      by T-agglutination method. This research consisted of 5,866 strains of scarlet
      fever-patients (scarlet fever-strains), 450 of child-patients (child-strains),
      141 of adult-patients (adult-strains) and 409 strains of the indistinct. The
      results were summarized as follows: 1. Total of 6,866 strains were classified to
      sixteen kinds of T-types such as T12 (44.1%), T4 (21.7%), T1 (9.2%), T6 (4.4%),
      T3 (2.8%), T22 (2.1%), T18 (1.9%), T28 (1.6%) & others. This pattern of type
      distribution, three prevailing types of T12/T4/T1, have been reported in other
      areas generally. But original increase of isolation rates of strains of some T
      types as T6, for example, also appeared in Sapporo. 2. Long-term observations
      demonstrated that the isolation rates of individual T-type, especially T4 or T1,
      had been forming a small epidemic-wave having a 4 to 8 year-interval and these of
      type T3 or type T6 on the other hand were repeating sudden prevalence every
      several years. 3. The isolation rates of type T12 or type T4 in scarlet fever
      strains, were significantly higher than in child-strains or adult-strains. It was
      shown that Type T1 was distributed widely irrespective of patient-group and age
      group. It was also characteristic to be distributed to many T-types in adult
      strains.

PMID- 11321776
TI  - [Long-term observations on type distribution of clinical isolates of beta
      hemolytic streptococci in Sapporo. II. Type distribution of Group B streptococci
      during the fifteen-year period between 1985 and 1999].
AB  - During the fifteen-year period between 1985 and 1999, a total of 1,985 strains of
      Group B Streptococci isolated in Sapporo City General Hospital were classified by
      agglutination method. The results were summarized as follows: 1. Type
      distribution of 1,513 isolates of group B streptococci in and after 1992 when
      type NT6 and type JM9 were started to be typed for the first time was as follows;
      according to rate isolation it was in the order of type NT6 (412 strains 27.3%),
      JM9 (257 17.0%), III (220 14.5%), Ia (182 12.0%), following IV, Ib, V and II. 2.
      As for proportion of origin-materials of isolates, vaginal discharge was 49.5%,
      urine 26.8%, throat swab 6.8%, sputum 6.6%, pus or exudate 4.2%, blood or spinal
      fluid 1.8% and stomach contents was 1.3%. A proportion of vagina-origin strains
      went up to 55% in the second half (1992-1999) from 23% in the first half (1985
      1991). 3. In type distribution of isolates in terms of origin-materials, the
      proportion of type III was significant by high in the stomach contents and blood
      and spinal fluid. Proportion of type Ia was significant by high in the sputum or
      throat swab. 4. Thirteen out of 28 strains (46.4%) from newborns were type III; 3
      out of 4 (75.0%) from spinal fluid, 5 out of 10 (50.0%) from blood, 5 out of 13
      (35.7%) from stomach contents.

PMID- 11321777
TI  - [Reduction of medical resources utilization by influenza vaccination for
      hospitalized elderly patients].
AB  - In order to evaluate the economic efficacy of influenza vaccination for the
      elderly inpatients, we have investigated the health insurance fee of elderly
      inpatients in Japan. It was revealed that the health insurance fee varied by
      patients largely, ranging from 7,000 yen to 90,000 yen. Primary reason of this
      variation was due to the existence of the same effective drugs with variant
      prices and there were no rules concerning the period of drug medication. Thus, it
      was found that it would be improper to use the medication fee as a measure in
      evaluating the effects of influenza vaccinations. In this study, we used the
      length of days of testing and medication such as oral antibiotics, blood cell
      count, etc. as a measure to evaluate the effect of influenza vaccination. We
      compared these measures among elderly hospitalized patients with influenza
      vaccination or without influenza vaccination by ADL. Mean length of days of oral
      antibiotics was 2.64 (+/- 6.40) days for those with vaccination, and 3.92 (+/-
      7.31) days for those without vaccination. Mean length of days of injection
      antibiotics was 2.52 (+/- 5.53) days for those with vaccination, and 8.82 (+/-
      15.1) days for those without vaccination. Mean length of days of cells blood
      counter was 2.63 (+/- 2.22) days for those with vaccination, and 4.44 (+/- 3.20)
      days for those without vaccination. Mean length of days of chest X-ray was 1.30
      (+/- 2.07) days for those with vaccination, and 2.56 (+/- 3.49) days for those
      without vaccination. These results suggest that influenza vaccination reduces
      medical utilization of resources. It was also revealed that influenza vaccination
      is most effective when elderly patients who are bed-bound are vaccinated.

PMID- 11321778
TI  - [Clinical analysis of neutropenic fever associated with hematological disorders].
AB  - We evaluated the efficacy of combination therapy with sulbactam/cefoperazone
      (SBT/CPZ) and amikacin sulfate (AMK) in eligible patients with hematological
      disorders of neutrophil count less than 1,000/microliter. The clinical efficacy
      rate in 157 evaluated patients was 65.6%. The clinical efficacy rates were
      related to neutrophil counts and serum albumin levels at the 1 week later. The
      clinical efficacy rates were 87.1% in patients with neutrophil counts over
      500/microliter and 34.8% in patients with serum albumin levels under 3 g/dl after
      1 week. G-CSF treatment were not significant but tended to be more effective in
      patients with sepsis, and the neutrophil counts increased significantly. The
      group using G-CSF before the antibiotic treatment had a high clinical efficacy
      rate. It is suggested that G-CSF is effective in patients with neutropenia with
      the high risk to infection and in those who already have severe infections.

PMID- 11321779
TI  - [Clinical analysis of patients with community-acquired pneumonia requiring
      hospitalization classified by age group].
AB  - We classified 1017 patients with community-acquired pneumonia requiring
      hospitalization experienced in Kawasaki Medical School Kawasaki Hospital during
      the past 15 years into five age groups (< or = 54 years old, 55-64 years old, 65
      74 years old, 75-84 years old, > or = 85 years old). With particular emphasis on
      the elderly patients, we then compared the clinical and microbiological findings
      in the five groups. The results were as follows; (1) Half of patients in the over
      85 years old group were bed-ridden. (2) The proportion receiving antibiotics
      before hospitalization decreased with age. (3) There were striking atypical
      pneumonic symptoms, such as dyspnea and consciousness disturbance in the two age
      groups over 75 years old. (4) Hypotension (shock) increased with age. (5) Markers
      of nutritional conditions, such as serum protein, albumin, cholinesterase, and
      hypoxia remarkably increased in the two age groups over 75 years old. (6) There
      were no significant differences in the isolation rate of etiological
      microorganisms. (7) The number of polymicrobial agents in the < or = 54 years old
      group was lower than that in the other age groups. (8) Mycoplasma pneumoniae was
      most significantly higher in < or = 54 years old group, Haemophilus influenzae in
      patients 55-64 years old, and Streptococcus pneumoniae in both 65-74 and 75-84
      years old groups. (9) The isolation rate of MSSA, gram-negative bacilli such as
      Klebsiella pneumoniae, Pseudomonas aeruginosa, respiratory viruses increased with
      age. (10) The amount of sepsis increased with age. (11) The prognosis was poor in
      the two groups over 75 years old because the mortality rate (over 10%) was higher
      that for the other age groups.

PMID- 11321780
TI  - [Isolation and incidence of Cryptosporidium and Giardia from river water].
AB  - A study was conducted during the period from July to October in 1999, surface
      water samples were collected from 13 rivers in Hyogo Prefecture serving as tap
      water sources and examined for Cryptosporidium oocysts and Giardia cysts using
      the immunomagnetic separation method. In 9 (69%) of the 13 rivers,
      Cryptosporidium oocyst was detected. Giardia cyst was detected in 5 (38%) of the
      13 rivers. The Cryptosporidium oocyst positive rate was comparable to that of
      fecal bacteriological indicators, which was also examined and detected in 10
      (77%) of 13 rivers. Water samples were collected at 69 points in the 13 rivers.
      Cryptosporidium parvum oocyst was detected at 38 (55%) of the 69 points,
      demonstrating widely spread contamination. Comparing 3 areas which were divided
      on the basis of agricultural circumstance as well as geographical locating, the
      Cryptosporidium positive rate varied widely according to the area, ranging from
      37% to 100%. To elucidate the reason for these differences, the relationship
      between positive rate and the species and number of livestock animals raised in
      each respective region was investigated. The results showed a strong correlation
      (r = 0.91) between the number of raised cattle and contamination with the rate of
      Cryptosporidium in each area. Furthermore, genetic analysis by PCR-restriction
      fragment length polymophism method revealed that C. parvum oocyst detected in the
      rivers studied was the bovine type, probably indicating that the oocyst was
      excreted from the cattle in the river basins. The degree of contamination with
      Cryptosporidium in river water was comparable to that of fecal bacteriological
      indicators, suggesting the possibility that fecal bacteriological indicators
      examination might be used as a criterion of Cryptosporidium contamination.

PMID- 11321781
TI  - [A case of secondary meningoencephalitis associated with Mycoplasma pneumoniae
      infection].
AB  - An 11-year-old girl was admitted to our hospital with complaint of disturbance of
      consciousness and muscle weakness. We diagnosed her as having meningoencephalitis
      because of the pleocytosis in the cerebrospinal fluid (CSF) and diffuse slow EEG
      waves. Laboratory tests in admission showed that serum passive hemagglutinin
      titer to Mycoplasma pneumoniae (M. pneumoniae) was 1:5,120, serum antibody titer
      to galactocerebroside (Gc) was 1:160, and CSF interleukin-6 (IL-6) level was
      20,500 pg/ml, but a specific DNA to M. pneumoniae was not detected in CSF using
      the polymerase chain reaction. Cranial and whole spine MRI were unremarkable.
      These results suggest that anti-Gc antibody and IL-6 play some roles in the
      development of mycoplasmal central nervous system involvement.

PMID- 11321782
TI  - [A survival case of severe Legionella longbeachae pneumonia].
AB  - A 56-year-old Japanese male was admitted to Toyohashi Municipal Hospital because
      of fever, cough, and dyspnea. Chest X-ray film showed bilateral alveolar
      infiltrates. He suffered from severe hypoxemia and was given a diagnosis of acute
      respiratory distress syndrome. He was also complicated with disseminated
      intravascular coagulation and pseudomembranous colitis. He fully recovered by
      intensive treatment with antibiotics, mechanical ventilation and endotoxin
      eliminating therapy. Legionella longbeachae was isolated from his respiratory
      specimens and was regarded as the etiologic agent of his pneumonia.

PMID- 11321783
TI  - Mixed infection of Malariae Malaria and falciparum Malaria.

PMID- 11321784
TI  - [Comparison of the amount of nursing and caregiving at home for cancer patients
      and for patients with cerebrovascular disease].
AB  - OBJECTIVE: This study was carried out to qualify and quantify the amount of care
      estimated to be needed by the nurse and home-helper, the amount actually being
      given and the amount demanded by patient with cancer or cerebrovascular disease
      under condition of nursing and caregiving at home. METHODS: Fifty-five patients
      with cancer and fifty-five with cerebrovascular disease registered at Visiting
      Care Stations in Aichi, Nagano and Tokyo, under nursing services of visiting
      workers dispatched by the respective station during the test period, were
      studied. A survey was conducted from September-December 1998 for cancer patients
      and from January-May 1999 for cerebrovascular disease patients. During the same
      periods, surveys of visiting nurses and home-helpers were conducted on the kinds
      and amount of service actually given and estimated to be needed, with
      questionnaire completed using a self-entry system. Addition of surveys was
      conducted with a visiting nurse's home-interviewing system. Items surveyed were
      sex, age, stage of disease, services given by family members and/or by visiting
      nursers and home-helpers, and the mean person-hours for each service. CONCLUSION:
      1. The amount of excess burden placed on the families of patients with
      cerebrovascular disease was significantly greater than with cancer patients (P <
      0.01, rank sum test). 2. Demands on nurses by cancer patient families were
      greater than those on home-helpers (P < 0.01, rank sum test), for daily attendant
      care, counseling and guidance, and coordination. 3. Demands from families of
      cerebrovascular disease patients on home-helper were greater than those on nurse,
      for daily attendant care, assistance in medical treatment, and counseling and
      guidance.

PMID- 11321785
TI  - [Positive perceptions encouraging continued caregiving at home among family
      caregivers].
AB  - PURPOSE: Few data are available on factors encouraging continued caregiving at
      home, especially in relation to positive perceptions of caregiving and the care
      burden. This study was conducted to explore this question. METHODS: We collected
      data from forty caregivers using Visiting nursing station, with structured
      interviews conducted at home. RESULTS: 1. Sixty-five percent of caregivers had
      positive perceptions of the worth and enjoyment of their work in caregiving. 2.
      Encouraging continued caregiving was associated with positive perceptions and
      these are relatively independent of the care burden. 3. Caregivers who had high
      encouraging continued caregiving were spouses or children of the clients. They
      had positive attitude to caregiving, an intention to use social services and
      satisfaction in caregiving. 4. Events from which caregivers felt worth and
      enjoyment in their work were improvement of client's health conditions, gratitude
      in client response, learning of care skills and strengthening bonds of family
      relationship. CONCLUSION: The findings suggest it is important to approach
      caregivers for the positive perceptions, rather than simply by decreasing burden.

PMID- 11321786
TI  - [A study on the transmission of MRSA among the family members including clients
      of visiting nurse and related infection control].
AB  - PURPOSE: The purpose of the study was to clarify MRSA (methicillin-resistant
      Staphylococcus aureus) transmission among clients, receiving nursing care from
      visiting nurse stations, and family members, as well as to determine MRSA
      positive rates of visiting nurses themselves and their handwashing habits.
      METHODS: The subjects were 131 clients who had utilized 32 visiting nurse
      stations, and had tested MRSA positive in our previous study performed 2-5 months
      earlier. The presence of MRSA in the nasal passages was investigated in 15 of the
      131 MRSA positive clients and the 24 family members who had agreed to cooperate.
      Antibiotic sensitivity tests of the involved strains of MRSA were conducted using
      14 antibiotics to allow antibiotic resistance patterns to be compared. 148 nurses
      who worked at 18 visiting nurse stations were also screened for MRSA in their
      nasal passages. In addition, a self-administered questionnaire was filled in
      concerning their handwashing habits. RESULTS: Out of 15 clients from whom MRSA
      was isolated in the previous study, 9 became MRSA positive (60.0%), and this was
      the case for 6 family members, living with 4 of them. The antibiotic resistance
      patterns coincided among the family members of 3 families, suggesting MRSA
      transmission among the client and his/her family member(s). MRSA transmission was
      shown not to be influenced by the ADL (activities of daily living) of a client
      nor by the content or time of the care provided by family member(s). As for
      visiting nurses, MRSA was isolated from 1 out of 148 (detection rate: 0.7%). The
      practice rate for handwashing was 91.2% after visiting as compared to 22.1%
      before visiting, and 93.4% after care as compared to 37.5% before care; the
      differences were significant (P < 0.001). The most frequently used handwashing
      procedures included handwashing with soap, povidone iodine and other
      disinfectants. The practice rate were 94.9% in visiting nurse stations and 91.2%
      in clients' homes. There was no significant difference between the procedures in
      these settings. DISCUSSION: Family members who are living with MRSA carriers are
      in danger of MRSA transmission irrespective of the content of the care,
      suggesting the need to prevent spread into compromised hosts or the community. On
      the other hand, visiting nurses are seldom infected with MRSA, and transmission
      of MRSA from nurses to clients is a rare event. This study showed, however, a low
      rate of handwashing before client contact. The possibility of cross infection
      from the hands of visiting nurses to their clients therefore needs further study.

PMID- 11321788
TI  - [Questionnaire on the Internet for public presentation on medical information.
      The difference on recognition of general medical information and gene
      information].

PMID- 11321787
TI  - [Characteristics of heterosexually acquired AIDS in Japan. An inter-country
      comparison using AIDS Surveillance data].
AB  - OBJECTIVES: To identify epidemiological characteristics of heterosexually
      acquired AIDS in Japan, with emphasis on potential influence on future trends.
      METHODS: National AIDS Surveillance data in Japan were compared with those in the
      UK and US, where detailed information is available from well-established
      surveillance procedures. Data on AIDS cases diagnosed until the end of 1996,
      particularly those acquired heterosexually, were analyzed by year of diagnosis,
      gender and age group. RESULTS: The number of heterosexually acquired AIDS cases
      in Japan has continued to increase, while those in the UK and US leveled out or
      decreased recently. The increase during a two-year period after reaching a
      certain number of cases per year was found to be 2.3-fold in Japanese, 2.4-fold
      in UK whites and 5-fold in US whites. The male to female ratio (M/F) for
      heterosexually acquired AIDS was 6.3 among Japanese, while the ratio was 1.1 and
      0.5 in the UK and US, respectively. The age distribution at AIDS diagnosis
      demonstrated a peak from 35 to 54 years of age among Japanese males, as compared
      to 30 to 34 among males in the UK and the US. No significant difference was
      apparent in the age distribution among females in the three countries.
      CONCLUSIONS: The relatively small number of AIDS cases in Japan is attributable
      to the late introduction of HIV and the limited chance of heterosexual
      transmission from homosexual/bisexual men and injecting drug users. In addition,
      transmission has probably most often occurred between middle-aged Japanese males
      and non-Japanese females. As there is a growing risk of HIV infection among
      Japanese females and young Japanese males, new prevention strategies targeting
      these groups are urgently required.

PMID- 11321789
TI  - [Diagnosis and microsurgical treatment of intramedullary spinal cord tumors].

PMID- 11321790
TI  - [Surgical treatment for symptomatic arachnoid cysts].
AB  - During the period from 1983 to 1999, 12 patients with symptomatic arachnoid cyst
      were treated. The mean patient age was 20.6 years. The most common location was
      the middle fossa (10 cases). Initial CT scan revealed associated subdural hygroma
      in 7 patients and hydrocephalus in one. Clinical symptoms were related to
      increased intracranial pressure, cranio-megaly and seizure. One infant with a
      huge arachnoid cyst was treated, using a cystoperitoneal (CP) shunt. Four
      patients underwent membraectomy. Combination CP shunt and membraectomy was
      performed in 5 patients. The remaining 2 arachnoid cysts were complicated with
      subdural hygroma and, initially, they were observed conservatively, but hygroma
      gradually changed to hematoma. One was treated by irrigation and the other
      hematoma was spontaneously absorbed. Significant complications included extensive
      subdural effusion in one patient, contralateral chronic subdural hematoma in two,
      intracranial hypotension in two, and shunt dependency in one. There were no
      recurrences during the follow-up period (mean 3.6 years).

PMID- 11321791
TI  - [Educational level of patients with germ cell tumor radiated in childhood].
AB  - In order to estimate the influence of radiotherapy on the intellectual
      development of children with brain tumor, we investigated the educational level
      of 21 patients with germ cell tumor who had undergone radiotherapy. They were
      divided into three groups in accordance with their age at the time of radiation;
      under school age group (under 6 years of age), elementary school age group (from
      7 to 12 years of age), and junior high and high school age group (from 13 to 18
      years of age). There were 2 cases in the under school age group, one of them
      graduated from high school and the other is presently a junior high school
      student. There were 5 cases in the elementary school age group. 3 of these
      graduated from university, 1 is presently a university student and 1 is a high
      school student. There were 14 cases in the junior high and high school age group.
      2 of these are university students, 7 graduated from high school, 1 is presently
      a junior high school student, and 4 died because of tumor progression. The mean
      period of hospitalization of the patients who have been admitted to university
      was 63.0 days, and that of patients who have not been admitted university was 135
      days. There is a statistical difference (p < 0.05). It could be concluded that
      the period of hospitalization rather than radiotherapy seemed to influence the
      educational status of children with brain tumor.

PMID- 11321792
TI  - [Memory disturbance caused by medial temporal lesion].
AB  - The memory disturbance caused by medial temporal lesion is reported concerning 6
      cases of cerebral hemorrhage, infarction, brain tumor, and contusion. The memory
      disturbance was significant compared with the patient's intact orientation and
      normal intelligence. In the category of memory, recent memory was more markedly
      disturbed than the immediate or remote memory. From the viewpoint of the lesion,
      the memory disturbance was more severe when, in addition to the hippocampus, the
      entorhinal gyrus or amygdala was damaged. The visual memory disturbance was mild
      and no difference was observed in the verbal or visual memory according to
      whether the lesion was right or left. The memory disturbance was usually
      transient and marked improvement was observed in some cases.

PMID- 11321793
TI  - [Successful treatment with bypass and interventional surgery for a ruptured
      pseudo carotid artery aneurysm after transsphenoidal surgery: a case report].
AB  - We report case of a patient who suffered a pseudo internal carotid artery (IC)
      aneurysm following transsphenoidal surgery. He was successfully treated with
      bypass surgery and IC occlusion involving the pseudoaneurysm using Guglielmi
      detachable coils (GDCs). This 50-year-old man with recurrent FSH-releasing
      pituitary adenoma suffered profuse arterial bleeding during transsphenoidal
      surgery. The hemorrhage was managed, using oxidized cellulose with bio-bond. His
      postoperative course was uneventful, but, he developed massive epistaxis 20 days
      after surgery. Cerebral angiograms showed a pseudoaneurysm arising from the C4
      portion of the left IC. He could not tolerate the balloon occlusion test. Using
      GDCs, we immediately performed left IC occlusion involving the pseudoaneurysm
      followed by bypass surgery between the left EC and the left middle cerebral
      artery. Postoperative angiograms showed that the pseudoaneurysm was completely
      occluded and the bypass was fully patent. When massive arterial bleeding is
      encountered during transsphenoidal surgery, the patient should be carefully
      monitored to detect early the development of a pseudoaneurysm. When such an
      aneurysm is found or has ruptured, interventional surgery has proved effective in
      the management of this complication.

PMID- 11321794
TI  - [A case report of hemiparesis due to compression of the medulla oblongata by an
      elongated vertebral artery].
AB  - The authors report a case of a 53-year-old woman who developed symptoms and signs
      of compression of the left medulla oblongata by the elongated and curved left
      vertebral artery with normal diameter. Twelve days before admission to the
      hospital, the patient suddenly noticed severe occipital-nuchal headache and
      nausea with vomiting, while she was unloading a burden. Neurological examination
      revealed left facial hyperalgesia, right hemihypesthesia and mild right
      hemiparesis. Hoarseness was observed, but the movement of the uvula and tongue
      was normal. Hypertension was noticed (180/100). Cerebral and vertebral
      angiography revealed no aneurysm, but demonstrated an elongated and curved V4
      portion of the left vertebral artery with normal diameter. Coronal plain of T2
      weighted image of MRI and CT scan with metrizamide administered into the CSF,
      clearly demonstrated an elongated and curved left vertebral artery compressing
      the ventro-lateral portion of the left medulla oblongata, neurovascular
      decompression of the V4 from the medulla oblongata was performed. Through the
      operating microscope, it was observed that the elongated and curved V4 portion of
      the left vertebral artery with normal configuration was compressing the left
      medulla oblongata ventro-laterally, making a compression notch at the outlets of
      the cranial nerves IX and X. Transposition of the V4 portion was impossible. Some
      pieces of Taflon felt, thick enough to prevent the pulsatile movement of the V4
      from compressing the medulla oblongata, were inserted between the V4 and the
      medulla oblongata. Two months after the operation, the patient's right
      hemiparesis and sensory disturbances were gradually improving and her blood
      pressure had become normal. The authors emphasize that, among patients with
      symptoms and signs of compression of the medulla oblongata, there is at least one
      patient for whom neurovascular decompression was an effective treatment.

PMID- 11321795
TI  - [Middle fossa arachnoid cyst presenting an interesting clinical course: a case
      report].
AB  - The mechanism of the disappearance of arachnoid cysts is not fully understood. We
      report a case of arachnoid cyst which disappeared after head injury. A 28-year
      old male was found to have an arachnoid cyst in the left middle fossa following
      head injury. We followed him up, because he had no symptoms. Two weeks later, he
      suffered from severe headache. CT image showed a dilatation of the subdural
      space, and his symptom deteriorated. We performed subdural-perifocal shunt, but
      one month after, he developed a subdural hematoma. The subdural hematoma was
      irrigated through a burr hole. His symptom disappeared post operatively. Two
      months later, CT image showed the disappearance of subdural hematoma and the
      arachnoid cyst. This case suggested one of the mechanisms involved in the
      disappearance of arachnoid cyst after head injury.

PMID- 11321796
TI  - [Extraaxial primary malignant lymphoma associated with calcified chronic subdural
      hematoma: a case report].
AB  - The authors report the case of a 54-year-old male with extraaxial primary
      malignant lymphoma associated with calcified chronic subdural hematoma. He slowly
      developed progressive headache accompanied by a bulge in the left forehead. Skull
      radiogram showed a large biconvex calcification in the left frontoparietal
      region, with concave change in the overlying bone. Computed tomograms and
      magnetic resonance images revealed a left frontoparietal chronic subdural
      hematoma surrounded by a calcified rim, with marginal enhancement in the frontal
      portion extending upward to the subcutaneous tissue through the underlying bone.
      The lesion was suspected to be an infectious calcified hematoma. The patient
      underwent a craniotomy for the removal of the hematoma. It was observed that the
      tumor was located mainly in the epidural and subdural space. The extent of the
      tumor corresponded with the enhanced area of the lesion in the preoperative
      neuroimages. The histological diagnosis was malignant lymphoma of B cell origin.
      General examination, which included bone marrow study and Ga scintigraphy, failed
      to prove systemic lymphoma. Extraaxial primary malignant lymphoma is extremely
      rare, and this is the first report of a lymphoma associated with calcified
      chronic subdural hematoma. The authors review the literature and discuss the
      clinical features and the pathogenesis of the lesion.

PMID- 11321797
TI  - [A case of infected subdural hematoma due to Campyrobacter fetus].
AB  - A 20-year-old male presented fever, nausea and headache 1 week after eating
      uncooked liver. On admission, it was revealed he had suffered a closed head
      injury 3 months before without unconsciousness. On admission, computed tomography
      scan showed a left chronic subdural hematoma. Gd-DTPA magnetic resonance images
      revealed unusual enhancement of the capsule and linear enhancement of the
      subarachnoid space. The patient underwent burr hole irrigation and drainage. The
      culture of the hematoma content showed Campylobacter fetus. Therefore, the
      diagnose was infected subdural hematoma. A drainage operation and administration
      of antibiotics were effective. Our case suggests that enhanced magnetic resonance
      images are useful for diagnosis and follow-up of infected subdural hematoma.

PMID- 11321799
TI  - [Intractable oral and maxillofacial pain].

PMID- 11321798
TI  - [A case of fatal herpes encephalitis presenting massive cerebral hematoma].
AB  - A 53-year-old woman was admitted to the hospital because of headache and
      disturbance of consciousness. She was afebrile. No inflammatory reaction was
      identified on serologic examination. Radiological findings showed acute-subacute,
      massive intracerebral hemorrhage in the right temporal lobe, compressing the
      brain stem contra-laterally. On the day of admission, she underwent a right
      temporal craniotomy for the removal of the mass lesion. The resected brain tissue
      demonstrated a small hemorrhage and edema accompanied by the infiltration of
      lymphoid cells into the subarachnoid space. Several days after surgery, the
      patient became lethargic and showed urinary incontinence. Late onset of fever and
      CSF findings suggested she was suffering from viral encephalitis. Serological
      findings, however, disclosed no antibody production against HSV, HZV, or CMV. For
      the diagnosis, a biopsy of the brain was carried out and herpes encephalitis was
      subsequently proved. Unfortunately, her condition deteriorated quickly and she
      died without anti-viral treatment.

PMID- 11321800
TI  - [Experimental study of secondary bone graft of alveolar clefts using bone
      morphogenetic protein (BMP)].
AB  - The purpose of this study was to evaluate the utility of recombinant human bone
      morphogenetic protein-2 (rhBMP-2) as a bone substitute on artificial alveolar
      clefts of adult Macaca fuscata monkeys. First, we created simulated alveolar
      clefts to represent human bilateral alveolar clefts, and then we implanted a
      mixture of rhBMP-2 and autogeneous particulate marrow cancellous bone (PMCB) into
      these models, as experimental groups. The mixture ratio was varied as follows
      (mixture ratio = rhBMP-2: PMCB). Group 1: rhBMP-2 alone. Group 2: Mixture of
      rhBMP-2 and PMCB (1:1). Group 3: Mixture of rhBMP-2 and PMCB (3:1). Group 4:
      Mixture of rhBMP-2 and PMCB (4:1). Positive control group: PMCB alone. Negative
      control group: PLGA (poly[L-lactide-co-glycolide] copolymer/gelatin sponge
      complex (PGS) alone. All animals were sacrificed 12 weeks after implantation and
      evaluated radiographically and histologically. The results were as follows. Bone
      bridge formation was not observed in Group 1, using rhBMP-2 alone, but it was
      observed in Groups 2, 3, and 4 using mixture of rhBMP-2 and PMCB. The vertical
      height of bone bridge formation in Group 4 was equal to that in the positive
      control group, roughly. The histological finding showed that the bone density of
      Group 4 was higher than in the positive control group, and the structure of
      cancellous bone turned into mature type. Bone formation and remodeling was active
      in Group 4. These results indicated that rhBMP-2 may be an effective substitute
      for autogenous PMCB in bone grafting into alveolar clefts.

PMID- 11321801
TI  - [Telomerase activity in oral squamous cell carcinoma and leukoplakia].
AB  - Telomeres, the physical ends of eukaryotic chromosomes, are important to
      stabilize the chromosome and have a unique simple repetitive DNA sequence, TTAGGG
      in humans. In most normal somatic cells, telomere length becomes 50-100 bp
      shorter with every cell division, and the cells finally go into senescence, while
      most cancer cells have been reported to maintain the length and thus are
      immortalized. Telomeres are replicated by a special transcriptase, called
      telomerase, which is composed of a template RNA (hTR) and at least two component
      proteins: hTERT (hEST 2/hTRT) and hTEP 1 (hTLP 1/hTP1). In the present paper, I
      examined the status of telomerase activities in oral squamous cell carcinomas
      (OSCCs), precancerous lesions, and also cell lines established from OSCCs, by
      using a non-radioactive PCR-based TRAP (telomeric repeat amplification protocol)
      assay. Telomerase activities were detected in 23 of 30 OSCCs, 8 of 17
      leukoplakias, 0 of 5 normal tissues, and in 8 of 8 OSCC cell lines and 0 of 5
      normal human keratinocyte cultures. These results indicated that telomerase
      activity might have some association with carcinogenesis and might be used as a
      tumor marker in OSCC.

PMID- 11321802
TI  - [A clinical and physiological evaluation of the unilateral occlusal deficit and
      its RPD treatment--a four-year follow-up study].
AB  - The aim of this study was to evaluate the longitudinal clinical and physiological
      changes in masticatory function for unilateral shortened arch, partially edentate
      patients by treatment with removable partial denture prostheses from the denture
      insertion over approximately four years of observation. The present follow-up
      study was conducted using objective findings and standpoints of unilateral
      occlusal deficit case, especially the clinical and physiological relation between
      musculature activity and changes of load center location periodically. The
      changes in masticatory functions by the muscle activity observed in EMG, and the
      occlusal loads and distributions throughout the arc, were surveyed by the
      modified Prescale system. The findings were statistically analyzed by using a
      sophisticated computer system that was developed by our research institute. The
      results were as follows: i) The functional musculature of unilateral shortened
      arc patients was clearly activated by using the unilateral RPD, and the
      improvements continued for four years after initial denture insertion. ii) The
      activation of masticatory muscle by denture-wearing over time, was in edentate
      side masseter, although the amplification of anterior temporal muscle was
      distinct in mandibular cases. iii) The muscle activity during rhythmical motion,
      such as tapping with denture-wearing, increased about two times than that of two
      and three years from the starting edentate value similarly to the clenching
      values within the measured period. iv) The masticatory efficacy of unilateral
      free end saddle prosthodontics was estimated using the changes in I-EMG values
      during peanut mastication. These findings suggested that the use of RPD
      accomplished an arc form and improved masticatory function for agglomeration of
      foods and masticatory efficiency over time.

PMID- 11321803
TI  - [Prefabrication of vascularized bone flap using bone morphogenetic protein
      (BMP)].
AB  - The purpose of this study was to produce newly vascularized bone, and to form the
      bone into the desired shape. Silicone molds given the shape of a cylinder were
      used to deliver collagen sheets impregnated with or without rhBMP-2. The
      superficial inferior epigastric neurovascular bundle in a Wistar rat was
      identified and sandwiched between the silicone molds. The molds containing
      collagen sheets impregnated with 10 micrograms of rhBMP-2 were used for the
      experimental purpose, and those without rhBMP-2 were used as a control. In some
      of the experimental molds, the neurovascular bundle was ligated at both proximal
      and distal sites of the molds. After 2 and 4 weeks operation, bone formation was
      detected macroscopically, radiologically, and histologically. As a result, newly
      formed bone was observed in all experimental sites without the ligation, and the
      shape of the bone was exactly the same shape as the silicone mold. Newly formed
      bone was supplied by the superficial inferior epigastric artery, whereas newly
      formed bone was not observed in the control and the ligated flaps. Newly
      vascularized and shaped bone was created by applying an osteoinductive factor to
      a neurovascular bundle. This study demonstrates that this experimental model
      could be a therapeutically potential approach for effective bone reconstruction.

PMID- 11321804
TI  - [Effect of an oral appliance for obstructive sleep apnea syndrome].
AB  - The purpose of this study was to evaluate the effect of an oral appliance (Sleep
      Splint) for obstructive sleep apnea syndrome (OSAS) patients, and to examine
      problems with this therapy. Fixed in the oral cavity, the Sleep Splint intends to
      reduce the occurrence of apnea and prevent blockage of the upper airway during
      sleep. In this study, the therapy using Sleep Splint was done for 50 patients (41
      men and 9 women) who had been introduced by the physician diagnosing with OSAS.
      Sleep monitoring around an oral appliance mounting was carried out, and the
      effect was evaluated. In addition, the ESS was used in respect of the evaluation
      of the daytime sleepiness. However, four patients stopped using the oral
      appliance due to serious discomfort in the maxillofacial region, and they were
      excluded from the study. Forty-six patients were classified into three groups by
      the seriousness of OSAS, or into two groups according to body fatness, and the
      difference of the effect between each group was compared. The results obtained
      were as follows. 1. As to the Apnea hypopnea index (AHI), Apnea hypopnea density,
      Oxygen desaturation, and ESS, there was statistically significant improvement
      regardless of the seriousness of OSAS and body fatness. 2. About all patients
      except for the patient group of the mild cases (AHI < 10), the occurrence of
      snoring showed the statistically significant improvement. These results indicated
      that oral appliance therapy was an effective treatment for OSAS.

PMID- 11321805
TI  - [Evaluation of the process of recovery of dental pulp after Le Fort I osteotomy].
AB  - Le Fort I osteotomy has been established by many studies and is generally used,
      but hypoesthesia of the dental pulp, the most common complication, occurs in
      almost all patients. As such, we examined dental pulp sensibility, pulpal blood
      flow, and histological changes, to elucidate the process of functional recovery
      of dental pulp after Le Fort I osteotomy. Monkeys (Macaca fusucata) were used in
      this study. The animals underwent Le Fort I osteotomy in their unilateral
      maxillae. Histological and angiographic examinations were performed to observe
      the postoperative changes in the maxillae and dental pulp. Postoperative pulpal
      blood flow was examined using a laser Doppler flowmetry. Postoperative pulpal
      blood flow, by a laser Doppler flowmetry, and dental pulp sensibility, by
      electrodiagnostics, in patients who underwent Le Fort I osteotomy, were also
      examined. Although nerve fibers observed in the dental pulp of the maxilla
      degenerated and disappeared by one week postoperatively, they reappeared sparsely
      from two to three months after osteotomy, and there were abundant nerve fibers by
      one year postoperatively. In the angiographic examination, blood supply to the
      maxillary dental pulp was maintained throughout the postoperative period. In the
      examinations of laser Doppler flowmetry and dental pulp electrodiagnostics,
      ischemia in the dental pulp for three or four days after osteotomy might delay
      the recovery of dental pulp sensibility. These results suggested that blood flow
      in dental pulp at three or four days after surgery may affect the recovery of
      dental pulp sensibility.

PMID- 11321806
TI  - [Immunohistochemical analysis of the p53 tumor suppressor gene product in oral
      leukoplakia].
AB  - Squamous Cell Carcinoma (SCC) is the most frequent malignancy in the oral cavity.
      p53 protein has been reported to be expressed at high levels in malignant
      lesions, while the level in premalignant lesions has yet to be determined. In
      this study, oral leukoplakia and oral SCC were examined. Seventy-four incision or
      excision samples from 43 cases diagnosed as leukoplakia, and 41 samples from 37
      SCC cases in the oral cavity, were obtained. All samples (formalin-fixed,
      paraffin embedded) were examined immunohistochemically for overexpression of p53
      protein with monoclonal antibody BP 53-12. As the result, 1. Twenty-two out of 43
      leukoplakia cases, and 29 out of 37 oral SCC cases, were positive for p53
      protein. 2. p53 protein was overexpressed in premalignant lesions, especially in
      the cases with moderate and severe epithelial dysplasia. 3. There was a relation
      between p53 protein expression and pathological features of leukoplakia
      (epithelial dysplasia), statistically. 4. There was a relation between p53
      protein expression and clinical features of leukoplakia, statistically. 5.
      Malignant transformation during clinical observation was seen in 11 cases. Nine
      out of 11 cases were positive for p53 even before malignant transformation. Since
      in cancer-development cases, p53 staining was detected even before malignant
      transformation of oral leukoplakia to squamous cell carcinoma, it is indicated
      that p53 accumulation occurred at a early stage of cancer-development. In
      conclusion, immunohistochemical analysis of p53 protein is suggested to be useful
      diagnostic procedure for oral leukoplakia, which may develop into oral SCC.

PMID- 11321807
TI  - [The relationship between oral manipulative skill and masticatory functions].
AB  - The purpose of this study was to elucidate the relationship between oral
      manipulative skill and masticatory function. Thirty-six dentate subjects and
      twenty complete denture wearers were instructed to make their fastest possible
      movement to bite a small rubber ball 8 mm in diameter repetitively on the right
      and left posterior teeth by turns. The time for this movement was measured using
      the Motion Capture System as an index of oral manipulative skill. Masticatory
      function was evaluated by assessing masticatory performance according to the
      sieving method. The results were as follows; 1. Among the dentate group, the
      cycle time of the movement and the masticatory performance of 2 g of peanuts (at
      10 and 20 masticatory strokes) were significantly correlated. Furthermore, the
      cycle time and the masticatory performance of 3 g of peanuts (at 10 masticatory
      strokes) were also correlated. 2. The cycle time for the complete denture wearer
      group was significantly longer than that of the dentate group. 3. Among the
      complete denture wearer group, the cycle time and the masticatory performance of
      2 g of peanuts (at 10 and 20 masticatory strokes) were significantly correlated.
      It is suggested that this index of oral manipulative skill might be related to
      masticatory function.

PMID- 11321808
TI  - [Influence of mastication on the amount of hemoglobin in human brain tissue].
AB  - The purpose of this study was to investigate the influence of mastication on the
      amount of hemoglobin in human brain tissue. Nine healthy volunteers (6 males and
      3 females) participated in this study. They underwent two tasks: 1) at rest, 2)
      gum-chewing. In seven of the nine (4 males and 3 females), experimental occlusal
      interference was applied to the first molar of the mandibule on the habitual
      masticatory side. They underwent the gum-chewing task. To evaluate the amount of
      hemoglobin, both the hemoglobin oxygenation state and blood volume during gum
      chewing were measured in the frontal region, using near-infrared spectroscopy.
      The amount of total-hemoglobin (blood volume) and oxyhemoglobin of subjects
      significantly increased during gum-chewing (p < 0.01). When the subjects finished
      gum-chewing, both levels returned to the original levels. When experimental
      occlusal interference was imposed on the subject, the amount of them
      significantly decreased compared with subjects without experimental occlusal
      interference (p < 0.05). The results suggested that increases of cerebral blood
      flow in the frontal region were not due to the mandibular movement, and that
      human brain activity caused by mastication was not only in the cortical
      masticatory area but also in the frontal region.

PMID- 11321809
TI  - [Role of psychosomatic medicine on oral and cranio-maxillofacial region].

PMID- 11321810
TI  - [Experimental study of periodontal tissue regeneration after the application of
      enamel matrix derivative in rat periodontal defects].
AB  - The purpose of this study was to evaluate periodontal wound-healing after the
      application of enamel matrix derivative (EMD) in rats. Periodontal defects were
      surgically created on the mesial side of the first maxillary molar of 24 male
      Long-Evans rats. EMD was applied to cover the denuded root surfaces in the
      experimental group. The contralateral molar was used for the control group, which
      received the same treatment without EMD. The rats were sacrificed at 2 weeks (8
      rats), 4 weeks (8 rats), and 8 weeks (8 rats) after the surgery. Demineralized
      paraffin sections were stained with Masson's trichrome. Histological analysis and
      histomorphometric measurements were performed on the periodontal sections. Using
      an immunohistochemical technique, the localization of osteocalcin (OC) was also
      examined. The formation of new cementum was statistically significant in the
      experimental group, especially new cementum with extrinsic fiber. Both acellular
      and cellular cementum were also rather strongly observed in the experimental
      group. Epithelial down growth was also strongly inhibited in the experimental
      group at 8 weeks after the surgery. OC-positive cells and matrix were limited at
      the bottom of the defects in the control group, while positive reaction was
      detected not only at the bottom but also spreading to the coronal portion of the
      defects in the experimental group. These results suggest that EMD has potential
      to promote cementum regeneration, especially fiber-inserted cementum, and to
      create a favorable environment that will promote periodontal regeneration.

PMID- 11321811
TI  - [A survey of awareness among new patients at the department of oral diagnosis and
      general dentistry].
AB  - The purpose of this study is to know the outline of clinical statistics of new
      patients at the Clinic for Initial Diagnosis/Emergency, Dental Hospital, Tokyo
      Medical and Dental University. We examined 1,001 new patients who visited our
      hospital from 19 October to 8 December 1995. The results were obtained as
      follows: 1. Our subjects were 1,001 patients, males were 357(35.7%) and females
      644(64.3%). The ratio of male to female was 1:1.8. 2. Concerning age
      distribution, the majorities were in their twenties and fifties in order. 3.
      71.5% of patients said it took less than one hour for them to come to our
      hospital. 4. The rate of introduced patients was 5.5% of all the new patients.

PMID- 11321812
TI  - [Clinicopathological studies on localized cemento-osseous dysplasia of the jaws].
AB  - The aim of this study was to clarify the entity of localized cemento-osseous
      dysplasia (COD), which occurs mainly in the posterior mandible. The clinical,
      radiographical, and histopathological features of 51 patients with COD were
      retrospectively studied. Radiographic features of the COD were classified into
      four types, according to the appearance of calcified bodies with related teeth
      and without related teeth. Pathological features of the COD were classified into
      four grades, based on the maturation of cemental masses. The results are
      summarized as follows: 1. Forty-four (86%) of the 51 patients were women. The
      mean age of the total group was 52.5 years, and 98% of COD lesions occurred in
      the posterior mandible. Clinical symptoms of COD were significantly more frequent
      in cases without related teeth (87%) than in cases with related teeth (55%). 2.
      The radiolographical calcification of COD was not related to the mean age, but it
      was related to the grade of histopathological maturation. 3. The four progressive
      stages of COD were recognizable both radiographically and histopathologically.
      The early stage is the osteolytic process, the intermediary stage is the
      cementoblastic process, the mature stage is the cementosclerotic process, and the
      end stage is necrotization of the cemental mass. These results suggested that
      localized COD in the posterior mandible had progressive stages both
      radiographically and histopathologically. The entity of localized cemento-osseous
      dysplasia was identified with focal cemento-osseous dysplasia, which was reported
      by Summerlin and Tomich.

PMID- 11321813
TI  - [Pulmonary vascular disease].
AB  - This review article discusses three topics related to pulmonary vascular disease:
      1) pulmonary vascular changes associated with portal hypertension, 2) ANCA
      associated pulmonary vasculitis, and 3) Takayasu's arteritis. Hepatopulmonary
      syndrome and pulmonary hypertension have recently been reported as pulmonary
      vascular changes accompanied with portal hypertension. Endogenous vasoactive
      agents that reach the pulmonary circulation through porto-systemic shunt vessels
      are thought to contribute to these vascular changes. In ANCA-associated
      vasculitis, hemorrhage, interstitial pneumonitis, and nodular lesions are common
      manifestations in the lung. In Takayasu's arteritis, CT occasionally demonstrates
      mosaic attenuation owing to pulmonary arteritis and peripheral reticulolinear
      changes probably due to thromboembolism.

PMID- 11321814
TI  - [Mediastinal cystic lesions: CT and MRI findings].
AB  - In this article we describe various approaches to the evaluation of mediastinal
      cystic lesions using CT and MRI. Although cystic lesions generally appear to be
      uncomplicated and not difficult to diagnose, we consider that there are certain
      pitfalls in differentiating them from solid lesions. It is important to pay
      careful attention to the location (including ectopic occurrence), CT attenuation
      and/or MR intensity, thickness of the wall, tear-drop shape or alternation of
      shape owing to intrathoracic pressure, and pseudoenhancement. We suggest that MR
      be recommended when the findings of CT are equivocal, as they were in 32 of our
      cases.

PMID- 11321815
TI  - The mediastinal courses of the bronchial arteries: helical CT evaluation.

PMID- 11321816
TI  - [Model of biological equivalent dose distribution modified by volume effect in
      radiotherapy].
AB  - This paper demonstrates that a biologically equivalent dose distribution
      including volume effect can be generated. Since the time-dose-fractionation (TDF)
      concept is convenient for comparing various radiation treatment schedules, TDF
      distribution maps are made on the basis of the physical dose distribution. On the
      other hand, the dose volume histogram is useful to evaluate volume effect, but is
      not necessarily an easy approach owing to the absence of spatial linkage. If
      distribution maps also representing the volume effect could actually be made, it
      would become easier to simultaneously predict both tumor control probability and
      the normal tissue complication rate. Because such tools should be very useful for
      planning radiotherapy, we proposed an experimental volume effect model. In this,
      one pixel is affected by all its surrounding pixels and the effect depends on the
      distance between pixels, volume, and the irradiated dose of another pixel. When
      the model was adapted to the conventional power law model, we could acquire a new
      equation with mathematical analysis. This permitted us to calculate the volume
      effect on each voxel within the treatment volume. Using a personal computer and
      treatment planning system, we calculated the "TDF-volume" distribution and drew
      maps based on this equation and the TDF values of each voxel for radiotherapy of
      a pelvic tumor.

PMID- 11321817
TI  - [Usefulness of multiphase helical CT in the diagnosis of pituitary microadenoma].
AB  - The purpose of this study was to determine the value of multiphase helical CT
      (MHCT) in the diagnosis of pituitary microadenoma. Twenty-two patients with
      clinically suspected microadenoma were examined. Coronal pre-contrast CT was
      initially carried out. Three series of helical scanning using 1-mm collimation, 1
      mm/s table speed, and 1-mm interval reconstruction covering the entire pituitary
      gland were performed with an intravenous injection of contrast medium.
      Immediately after MHCT, delayed CECT was performed. Twenty microadenomas (3-10
      mm, mean: 5.5 mm) were surgically confirmed. MHCT could depict all 20 tumors,
      while pre-contrast CT and delayed CECT showed 4 and 12 of 20 tumors,
      respectively. MHCT was useful in the diagnosis of pituitary microadenoma owing to
      its high spatial resolution and extensive coverage.

PMID- 11321818
TI  - [Three-dimensional CT angiography of the hepatic artery with multislice CT:
      differences in image quality according to scanning pitch].
AB  - Three-dimensional CT angiography was reconstructed from the hepatic artery using
      multislice CT, and the effect of pitch during scanning on the quality of obtained
      images was examined. We randomly divided patients into two groups, with images of
      one group scanned at helical pitch 3 and images of the other at helical pitch
      5.5. CT angiography was reconstructed by a volume-rendering technique. Evaluation
      was done visually, taking the sharpness of images of branches of the hepatic
      artery as a measure. Three-dimensional imaging scanned at pitch 3 tended to be
      better than that scanned at pitch 5.5.

PMID- 11321819
TI  - [Two cases of alimentary tract perforation owing to ingested foreign bodies:
      diagnosis by CT].
AB  - We report the CT diagnosis of two cases of alimentary tract perforation caused by
      the ingestion of foreign bodies. The first case was a common fish bone
      perforation of the ileum with postoperative scar. The second case was a rare
      perforation caused by the impact of an uncooked rice cake on sigmoid colon
      diverticula. Helical CT scan clearly revealed the fish bone as a linear high
      density area in the soft tissue between the right abdominal oblique muscles and
      ileum, and demonstrated the rice cake as high-density material in the bowel.

PMID- 11321820
TI  - [Lung involvement in rapidly progressive glomerulonephritis].
AB  - The purpose of this study is to evaluate pulmonary involvement in rapidly
      progressive glomerulonephritis (RPGN). Of 71 patients in whom RPGN was diagnosed,
      32 (45.1%) had pulmonary involvement: 12, alveolar hemorrhage (AH) (16.9%); 10,
      interstitial pneumonia (IP) (14.1%); four, chronic bronchial lesions (5.6%); two,
      consolidation (2.8%), and four, old inflammatory lesions (5.6%). Investigation of
      which organ of the twelve AH patients, the kidney or the lung, was the first to
      be involved, showed that the lung preceded in one patient, the kidney was first
      in three, and the lung and kidney occurred at the same time in the other eight.
      Of the ten IP patients, the lung preceded in eight, the kidney was ahead in two,
      and lung and kidney were simultaneous in one. Three patients had a history of
      pneumoconiosis, and two had acute progressive IP. Seventeen (45.9%) of 37
      patients who tested positive for antineutrophil cytoplasmic autoantibodies (MPO
      ANCA) had lung involvement, and three (30.0%) of the ten patients who tested
      negative for MPO-ANCA, PR 3-ANCA and anti-GBM antibody also had lung involvement.

PMID- 11321821
TI  - [A case of metachronous multiple primary lung cancers coexistent with atypical
      adenomatous hyperplasia].
AB  - A seventy-year-old woman was admitted for an abnormal chest shadow on a routine
      radiograph. She had undergone left upper lobectomy with mediastinal lymph node
      resection (R2a) for lung cancer (stage I), eight years before. We diagnosed this
      cancer as well differentiated papillary adenocarcinoma, and it coexisted with a
      focus of atypical adenomatous hyperplasia (AAH) in the resected material. We had
      been following up this patient with chest radiography, CT scanning, and tumor
      marker tests, but eight years after her first operation, we found a small nodular
      lesion in the left upper field (S6). This nodule was not diagnosed with
      fiberoptic bronchoscopy. Because we could not exclude primary lung cancer or
      intrapulmonary metastasis (eight years ago), we performed partial lung resection
      on the left S6 nodule. Histopathologically, the diagnosis was well differentiated
      papillary adenocarcinoma of the lung, coexisting with a small hyperplastic focus
      in the resected material. It was very difficult to diagnose whether these two
      cancers were metachronous multiple primary lung cancers, or one primary and its
      intrapulmonary metastasis. In a retrospective study, an immunohistochemical
      examination employing Ki-67, PCNA, p 27 and p 53 was performed in order to
      differentiate between metachronous multiple primary lung cancer and
      intrapulmonary metastasis. But we found AAH in the same resected lung eight years
      ago, and suggested the possibility that another small, atypical focus had
      developed into a malignancy. We report a case of metachronous multiple primary
      lung cancers and review the relevant literature.

PMID- 11321822
TI  - [Bullous sarcoidosis--a case report].
AB  - A 37-year-old man was admitted to our hospital complaining of dry cough and
      dyspnea. His chest radiographs showed severe bullous changes in the upper lobes
      and scattered small nodules in the lower. During the course of further
      examination, a spontaneous left pneumothorax developed in the lung, and video
      assisted thoracic surgery was performed to remove a bulla. Multiple noncaseous
      granulomas were seen and sarcoidosis was diagnosed. Here we report a case of
      pathologically investigated bullous sarcoidosis, which is rarely seen to generate
      bullae due to granulomatous lesions. Therefore, it is important to consider
      sarcoidosis in making a differential diagnosis when a diffuse lung disease with
      cystic change is encountered.

PMID- 11321823
TI  - [Bronchiolitis obliterans organizing pneumonia after adjuvant thoracic
      radiotherapy for breast cancer: a case report].
AB  - We report a case of recurrent cough and migratory pulmonary infiltrates in a 55
      year-old woman after adjuvant thoracic radiotherapy for breast cancer. The
      pulmonary infiltrates were initially limited to the area adjacent to the
      irradiated breast, but later migrated to the opposite lung. The diagnosis of
      bronchiolitis obliterans organizing pneumonia (BOOP) was made using a
      transbronchial biopsy, which disclosed intraluminal fibrosis in the distal
      airspace, together with a radiographic appearance typical of BOOP. This case was
      assumed to be in a series of reported cases of BOOP primed by radiotherapy.

PMID- 11321824
TI  - [A case of severe Legionella pneumonia monitored with serum SP-A, SP-D, and KL
      6].
AB  - A 67-year-old man was admitted for acute pneumonia on July 20th, 1999. Chest
      radiographs disclosed dense consolidation in the right lower lung fields. After
      admission, the pneumonia underwent rapid advance. On the basis of serological
      findings and cultures of pleural effusion and sputum, the patient was given a
      diagnosis of acute pneumonia caused by Legionella pneumophila 1 a. He gradually
      recovered from the pneumonia by means of chemotherapy using EM, RFP, Mino,
      gammaglobulins and steroids. The serum SP-A, SP-D, and KL-6 peaked on July 23rd,
      July 30th, and August 12th, respectively.

PMID- 11321825
TI  - [A case of rheumatoid lung disease in which lung involvement preceded arthritis].
AB  - A 75-year-old man was admitted because of dyspnea on exertion and diffuse
      pulmonary interstitial shadows. An open lung biopsy revealed unclassified
      interstitial pneumonia. The abnormal shadow subsided spontaneously. Three years
      later, however, rheumatoid arthritis developed with a simultaneous relapse of
      interstitial pneumonitis, which was alleviated by steroid therapy. We report here
      the rheumatoid lung disease that preceded the onset of arthritis, together with a
      review of the literature.

PMID- 11321827
TI  - [A case of Behcet's disease presenting with Hughes-Stovin syndrome (multiple
      pulmonary arterial aneurysms remitting with corticosteroid therapy)].
AB  - A 32-year-old male suffering from thrombophlebitis of the right leg was admitted
      to our hospital because of massive hemoptysis. Chest radiography showed multiple
      rounded opacities in the right lung field. Pulmonary angiography revealed
      multiple aneurysms of the right pulmonary arteries and thromboembolism of the
      left pulmonary artery. Venography demonstrated obstruction of the deep veins of
      the right leg and the right femoral vein, and deep vein thrombosis was diagnosed.
      A more precise diagnosis was Hughes-Stovin syndrome, that is, venous thrombosis
      especially of the vena cava, accompanied by single or multiple pulmonary arterial
      aneurysms in young patients. Furthermore, the patient had an aphthous ulcer in
      the oral cavity, an ulcer in the genital region, leading to a diagnosis of the
      incomplete type of Behcet's disease. Chest radiographs 3 months after the
      initiation of corticosteroid showed complete resolution of the aneurysms.
      Repeated pulmonary angiography also showed partial recanalization of the occluded
      arteries. This report describes this very rare case of Behcet's disease
      presenting with Hughes-Stovin syndrome.

PMID- 11321826
TI  - [A case of primary racemose hemangioma of bronchial artery with recurrent
      hemoptysis].
AB  - A 42-year old man was admitted to our hospital because of hemoptysis. Bronchial
      arteriography revealed a tortuous and dilated left bronchial artery with a shunt
      formation between the bronchial and pulmonary arteries. Bronchial artery
      embolization using a sponge was performed three times to treat the hemoptysis,
      but all attempts failed. The patient therefore underwent left lower lobectomy,
      after which no hemoptysis was observed. Histopathologically, the resected tissue
      showed no inflammatory change. Interestingly, abnormal vessels resembling
      arteriovenous malformations were also found. Although the embolization therapy
      was effective in several reported cases, we concluded that surgery was required
      for this patient with persistent hemoptysis because of the development of
      collaterals and a bronchial-pulmonary artery shunt.

PMID- 11321828
TI  - [Bronchiolo-alveolar cell carcinoma arising after active pulmonary tuberculosis'
      report of two cases].
AB  - We report on two patients diagnosed as having active pulmonary tuberculosis who
      later developed lung cancer. In both cases, the lung cancer was detected during
      the treatment of pulmonary tuberculosis. Both patients were initially considered
      to be experiencing exacerbation of pulmonary tuberculosis. Case 1 was seen in a
      74-year-old man. His chest roentgenogram revealed microscopic cavitary lesions
      with infiltration into both lung fields. His sputum tested positive for acid-fast
      bacilli. Although he was treated with isoniazid (INH), rifampicin (RFP),
      ethambutol (EB) and pyrazinamide (PZA), his general condition deteriorated, and
      the infiltrative shadows in the lung fields had expanded on subsequent chest
      radiography. Transbronchial lung biopsy (TBLB) yielded findings compatible with a
      diagnosis of bronchiolo-alveolar cell carcinoma. Case 2 occurred in a 52-year-old
      man. His chest radiograph revealed cavitary lesions with infiltration into both
      lung fields. His sputum also tested positive for acidfast bacilli. Despite
      medication with INH, RFP, EB and PZA, the infiltrative shadow in his chest
      radiograph increased in size. Bronchiolo-alveolar cell carcinoma was confirmed
      after examination of the sputum cytology. Case 1 was diagnosed as lung cancer 10
      months after being admission to the hospital, and Case 2, seven months after
      hospitalization. Recent discussion concerning the simultaneous occurrence of
      pulmonary tuberculosis and bronchogenic carcinoma suggests a high frequency of
      coexistence of the two diseases. However, the coexistence of active tuberculosis
      with bronchiolo-alveolar cell carcinoma, as in our cases, is rare.

PMID- 11321829
TI  - [A case of pulmonary Mycobacterium avium infection with a rapid-growing solitary
      node].
AB  - A 72-year-old man was admitted to our hospital because of an abnormal shadow on
      his chest radiograph. Computed tomography revealed a 3 cm solitary nodular
      opacity in the right S1. Bronchofiberscopy could neither give any specific
      histological findings nor bacteriological findings. This nodular shadow increased
      in size to 1.5 times that in the first chest radiograph. In addition, since there
      was no abnormal finding in the chest radiograph one year before, we performed
      partial pulmonary resection by video-assisted thoracoscopic surgery, taking into
      consideration the possibility that the solitary node was malignant. The
      pathological findings of the resected specimen were an epitheloid cell granuloma
      with Langhans giant cell and caseous necrosis. We could not detect any acid-fast
      bacilli or malignant cells. After surgery, M. avium was detected in a 6-week
      culture of the resected specimen. We treated the patient with RFP, EB and CAM for
      6 months. Outpatient follow-up revealed no relapse.

PMID- 11321830
TI  - [Early replacement of intravenous aminophylline administration with oral
      theophylline in treating acute exacerbation of asthma].
AB  - Intravenous (i.v.) administration of aminophylline has been used to relieve acute
      exacerbation of bronchial asthma for almost a century. Despite confidence in its
      effectiveness, controversy has arisen about its efficacy. We currently use
      aminophylline in the routine treatment of asthma since the drug is essentially
      useful. Continuous aminophylline infusion tends to be used rather haphazardly in
      hospital wards, and the criteria for termination of an infusion have not been
      clarified. We therefore attempted to determine: 1) whether continuous
      aminophylline infusion is actually beneficial, 2) whether the TDM (treatment drug
      monitoring) system can be used to establish a protocol for prescribed dosing
      after an early switch from i.v. to oral administration, and 3) whether adherence
      to the protocol would contribute to decreases in the duration of hospitalization
      and in medical expenses. Seventeen patients with acutely exacerbated asthma were
      enrolled in this study. Nine patients were prescribed oral theophylline on the
      second hospital day (p.o. group), while eight received continuous i.v.
      aminophylline (i.v. group). The serum theophylline concentrations were maintained
      in the therapeutic range in both groups. Peak flow, symptom scores, and QOL
      scores showed significant improvements in the p.o. group on the third hospital
      day. It might therefore be possible, by using the TDM system, to set the dosage
      of theophylline so that hospitalization is shortened.

PMID- 11321832
TI  - [Results of questionnaire on open disclosure to patients with malignant lung
      tumors comparison of responses before and after chemotherapy].
AB  - To investigate patient attitudes towards open disclosure of malignant disease, we
      conducted a questionnaire survey of 17 patients with malignant lung tumors, to
      whom the nature of their disease was revealed. The questionnaire used a 100 mm
      analog scale. Ten of the patients were treated by chemotherapy and their
      questionnaire results before and after treatment were compared. It was found that
      they were mostly satisfied about being truthfully informed and that, indeed, they
      were anxious to know their true diagnoses. They were also keen to have their true
      prognosis revealed, but not as much as the diagnosis. They also wished to be
      informed about treatment and its effects. These attitudes showed no marked
      changes resulting from the administration of chemotherapy, and we therefore
      concluded that chemotherapy itself had no influence on patients' feelings about
      disclosure. The questionnaire was well accepted and was useful in judging
      attitudes to open disclosure.

PMID- 11321831
TI  - [Prognosis of subacutely progressive interstitial pneumonia depends on the
      presence of focal usual interstitial pneumonia].
AB  - A retrospective follow-up study was conducted on patients with subacutely
      progressive interstitial pneumonia who underwent surgical biopsy. Pathologically,
      they were subclassified into subacute interstitial pneumonia (SIP) and SIP + F,
      which consisted of an SIP lesion and a focal usual interstitial pneumonia. The
      SIP group consisted of 35 cases and the SIP + F group, of 15 cases. The majority
      of patients in both groups were female and complained of dyspnea. Both groups
      showed increased neutrophil counts (8.8%, 6.3%), eosinophils (6%, 5.6%), and
      lymphocytes (43.1%, 42.3%) in bronchoalveolar lavage. Chest radiography generally
      demonstrated predominant lower lobe involvement together with shrinkage in both
      groups, and differentiation of the two was difficult before biopsy. All but one
      improved temporarily with steroid therapy, or spontaneously, in both groups. On
      further observation after temporary improvement, 27 cases (82%), did not show any
      worsening and 6 cases (18%) showed worsening (including death) in the SIP group,
      while 6 cases (43%) showed no worsening, though 8 cases (57%) worsened in the SIP
      + F group. Deaths in either group that were not related to the original diseases
      were excluded from the statistical analysis. We concluded that the presence of
      focal usual interstitial pneumonia in SIP lesions affects prognosis in patients
      with subacutely progressive interstitial pneumonia.

PMID- 11321833
TI  - [Proposal for a new method for evaluation of physical exercise capacity in
      patients with chronic respiratory disease].
AB  - We developed a new method of evaluating the tolerance for physical exercise in
      patients with chronic respiratory disease. Using a newly developed portable pulse
      oxymeter, with which we could measure kinetic energy (physical activity),
      calculated from the vertical acceleration involved in physical movements in the
      patient's daily life, we considered the correlation between the characteristics
      of the distribution of oxygen saturation (SpO2) and the degree of physical
      activity. The characteristics of SpO2 distribution in normal healthy subjects are
      uniform at all degrees of physical activity. In patients with chronic respiratory
      disease who complained of dyspnea on exertion, these characteristics became more
      uneven as physical activity increased. By comparing the characteristics of SpO2
      distributions at rest with those at certain degrees of physical activity, we
      could quantitatively evaluate the exercise tolerance of patients with chronic
      respiratory disease, while monitoring their physical activity and SpO2 in daily
      life, without burdening the patients with stress such as would be imposed by the
      treadmill test. This new method is applicable for determining the indications for
      home oxygen therapy. Its application in home health care could offer a useful
      evaluation of a patient's activities of daily living and also early discovery of
      aggravation of chronic respiratory failure.

PMID- 11321835
TI  - [Mammalian lectins in the innate immune system].

PMID- 11321834
TI  - [Scavenger receptor family and molecular mechanism of xenobiotic removal].

PMID- 11321836
TI  - [Scavenger receptors and pathogenesis of atherosclerosis].

PMID- 11321837
TI  - [Physiological roles of macrophage scavenger receptor type A I/II in vivo].

PMID- 11321838
TI  - [Role of class B scavenger receptor type I in phagocytosis of apoptotic cells].

PMID- 11321839
TI  - [Lectin-like oxidized LDL receptor LOX-1].

PMID- 11321840
TI  - [Oxidized low density lipoprotein receptors, including SR-PSOX, and
      atherogenesis].

PMID- 11321841
TI  - [Mechanism of removal of aged cells, oxidized cells and apoptotic cells through
      carbohydrate chains].

PMID- 11321842
TI  - [AGE and AGE-receptors].

PMID- 11321843
TI  - [Molecular cloning of CL-P1 gene].

PMID- 11321844
TI  - Cancer-related fatigue in children.

PMID- 11321845
TI  - Evaluating a model of fatigue in children with cancer.
AB  - This evaluation of a program of research on fatigue in children with cancer is a
      critique of the model developed as an outcome of the research. Emphasis is placed
      on the research methods as well as on the contribution to knowledge development
      related to pediatric cancer-related fatigue.

PMID- 11321846
TI  - Clinical applications of research on fatigue in children with cancer.
AB  - Fatigue is a prevalent problem in the pediatric oncology population but is
      probably under-recognized and undertreated. The research on fatigue in children
      with cancer presented in this issue offers a welcome exploration of the subject.
      Clinical nurses must begin to understand the causes and symptoms of fatigue, as
      well as supportive care measures for their patients. Fatigue can occur in
      children who receive chemotherapy, radiotherapy, and biotherapy, and in children
      who are treated with bone marrow transplantation. Education of the patient and
      family regarding the potential for fatigue is helpful in preparing them for the
      cancer experience. Factors that contribute to and alleviate fatigue can be
      identified for each patient, taking into consideration age, developmental level,
      and cultural background. Parents and patients, especially adolescent patients,
      may have differing opinions about what fatigue is and what may be helpful.
      Further research into fatigue in children with cancer is encouraged, especially
      in patients suffering from alterations in sleep or nutritional status, and in
      long-term survivors of childhood cancer.

PMID- 11321847
TI  - Consensus statements: analyzing a new model to evaluate fatigue in children with
      cancer.

PMID- 11321848
TI  - Developing a research program on fatigue in children and adolescents diagnosed
      with cancer.
AB  - Fatigue may be a universal experience for children and adolescents who are being
      treated for a malignancy. Sadly, it may also be the most unrecognized and thus
      unaddressed symptom experienced by this population. Giving adequate attention to
      this symptom has been stymied in part by the lack of a conceptual definition of
      fatigue in children and adolescents with cancer and the lack of a method to
      accurately measure their fatigue. This article provides a descriptive overview of
      a clinical research program on fatigue in children and adolescents with cancer
      that sought to develop conceptual and operational definitions of fatigue from the
      perspectives of the patient, parent, and staff. The link between these
      definitions and planned future fatigue intervention research is also described.

PMID- 11321849
TI  - Extrafine beclomethasone dipropionate breath-actuated inhaler (400
      micrograms/day) versus budesonide dry powder inhaler (800 micrograms/day) in
      asthma.
AB  - Hydrofluoroalkane-134a beclomethasone dipropionate extrafine aerosol breath
      actuated inhaler (Qvar Autohaler; BDP-AH) provides an alternative to
      chlorofluorocarbon metered dose inhalers or dry powder inhalers (DPIs). The aim
      of this six-week, open-label study was to determine whether BDP-AH demonstrates
      equivalent asthma control to twice the dose of budesonide (BUD)-DPI (Pulmicort
      Turbuhaler). Adults with symptomatic asthma inadequately controlled on BUD-DPI
      400 micrograms/day and beta-agonist were enrolled. Patients (n = 193) were
      randomised to receive 400 micrograms/day BDP-AH (n = 98) (two puffs of 100
      micrograms/actuation inhaler twice daily) or 800 micrograms/day BUD-DPI (n = 95)
      (two puffs of 200 micrograms/actuation inhaler twice daily). Both groups showed a
      statistically significant change from baseline in morning (a.m.) peak expiratory
      flow (PEF) at weeks 5-6 (p < 0.01), indicating study treatment improved a.m. PEF
      over prestudy 400 micrograms/day BUD. Changes from baseline in a.m. PEF at weeks
      5-6 were 15.9 l/min for BDP-AH and 14.2 l/min for BUD-DPI; the groups were
      statistically equivalent (90% CI -7.02-10.44; p < -0.001 [equivalence = within +/
      25 l/min]). Other efficacy assessments (evening PEF, FEV1, asthma symptoms, beta
      agonist use) confirmed the treatments were clinically equivalent. Thirty-nine
      (40%) patients on BDP-AH and 35 (37%) on BUD-DPI experienced at least one adverse
      event (p = 0.767). Four (4%) patients on BDP-AH and 3 (3%) on BUD-DPI reported
      increased asthma symptoms. BDP-AH at half the daily dose provided equivalent
      asthma control to BUD-DPI; both treatments were well tolerated.

PMID- 11321850
TI  - The old but reliable digitalis: persistent concerns and expanded indications.
AB  - Digitalis has been an old but reliable drug for 240 years. Concerns regarding its
      clinical indications and benefits still exist in the absence of a reduction in
      all-cause mortality. While intravenous digitalis is used without question in
      cases of atrial fibrillation, it is still controversial in sinus rhythm, despite
      the Digitalis Investigation Group (DIG) study showing a significant reduction in
      death and the need for hospitalisation for congestive heart failure in both
      diastolic and systolic dysfunction. The influence of digitalis in acute
      myocardial infarction, coronary artery disease and sudden cardiac death remains
      speculative. In cases of uncomplicated hypertension, it appears to prevent the
      onset of left ventricular dysfunction and myocardial infarction. Thus, digitalis
      can be a cost-effective agent with added benefits.

PMID- 11321851
TI  - Three-year update of sildenafil citrate (Viagra) efficacy and safety.
AB  - In the three years since its launch, sildenafil citrate (Viagra), an oral agent
      for the treatment of erectile dysfunction (ED), has been prescribed to more than
      10 million patients worldwide and has been further evaluated in clinical studies
      in diverse patient populations. Significant improvements in erectile function
      have been demonstrated in double-blind, placebo-controlled trials in patients
      with ED and underlying diabetes, cardiovascular disease, minor depression, spinal
      cord injury and multiple sclerosis. Promising results have also been reported for
      patients with treated prostate cancer, end-stage renal failure, Parkinson's
      disease, and spina bifida and in multiple organ transplant recipients. Accounts
      of sildenafil use in clinical practice and postmarketing data reflect clinical
      trial findings of effectiveness in a broad spectrum of ED aetiologies and overall
      good tolerability. As in the clinical trials, most adverse events associated with
      sildenafil use have been transient, mild or moderate effects that rarely lead to
      treatment discontinuation.

PMID- 11321852
TI  - Drugs for treatment of Alzheimer's disease.
AB  - Alzheimer's disease is already an international problem of enormous significance,
      with an estimated 500,000 sufferers in the UK alone. There are currently four
      licensed compounds available for the symptomatic treatment of mild to moderate
      Alzheimer's disease, yet there is still considerable debate over their
      effectiveness. A variety of anti-dementia agents affecting the various aspects of
      the disease are in development and the debate will continue over the potential
      rationing of such treatments in the future. Drugs developed from the cholinergic
      and glutamatergic hypotheses will be discussed, and a number of other potential
      treatments aimed at reducing the oxidative stress and inflammatory response
      associated with dementia will be reviewed. The arrival of these new treatments
      for Alzheimer's disease has focused attention on the management of dementia in
      general and has provided the catalyst for the widespread development of memory
      clinics to enable proper assessment of patients with dementing disorders,
      providing hope for both patients and carers.

PMID- 11321853
TI  - Insight into schizophrenia: planning mental health service provision for
      schizophrenia using a brief psychological intervention.
AB  - Six nurses were trained to deliver an Insight programme to patients with
      schizophrenia and their main carers. One outcome of the intervention was the
      highlighting of recommendations for future treatment. These were fed back on an
      individual basis through an exit letter to the patient's consultant psychiatrist
      and key worker. The individual treatment recommendations were then collated into
      a report for each site and presented to clinical coordinators and business
      managers. It is envisaged that the recommendations could be used by managers in
      developing a business case for future mental health provision in schizophrenia.
      The complete results of the study are due to be published in the near future.

PMID- 11321854
TI  - Stigma and discrimination: the silent disease.

PMID- 11321855
TI  - Acute adrenocortical crisis: three different presentations.
AB  - The adrenal cortex normally produces three principal steroid hormones: the
      glucocorticoid cortisol, the mineralocorticoid aldosterone, and a small quantity
      of sex steroids. In primary adrenocortical insufficiency, there is a deficiency
      of both cortisol and aldosterone with characteristic clinical and laboratory
      findings. In contrast, with a pituitary disorder there is isolated
      hypocortisolism, because its production is dependent on pituitary
      adrenocorticotropic hormone (ACTH), whereas aldosterone production is controlled
      by extracellular fluid volume, renin and serum potassium. Acute adrenocortical
      crisis is an absolute medical emergency and its presentation is not always
      typical. We describe three recent cases of acute adrenocortical crisis in our
      hospital who presented in three different ways in three different wards.

PMID- 11321856
TI  - Necrosis of the nasal ala after improper taping of a nasogastric tube.
AB  - Inserting a nasogastric tube during various abdominal procedures is a common
      maneuver to decompress the upper gastrointestinal tract. Improper placement and
      taping of the nasogastric tube results in excessive pulling on the nasal ala and
      subsequent pressure necrosis. This complication not only carries serious cosmetic
      morbidity, it is also preventable if a proper taping technique is employed.

PMID- 11321857
TI  - 'Always chew your chillies': a report of small bowel obstruction with
      perforation.
AB  - We report an unusual case of small bowel obstruction and localised ileal
      perforation caused by an undigested green chilli in a 43-year-old man presenting
      in accident and emergency.

PMID- 11321858
TI  - Multiple aneurysms associated with congenital rubella.
AB  - We describe the case of a woman with congenital rubella who presented with
      backache. Plain abdominal X-ray revealed calcification of a superior mesenteric
      artery aneurysm. Intra-arterial digital subtraction angiography demonstrated
      multiple aneurysms of the arteries to the upper and lower limbs and the viscera.
      We have not found another report in the literature of the association of
      congenital rubella with multiple aneurysms.

PMID- 11321859
TI  - Pelvic lipomatosis presenting as uraemic encephalopathy.
AB  - Pelvic lipomatosis is a benign disorder of unknown aetiology, characterised by
      deposition of mature fat in the pelvis. It has a variable natural history,
      manifesting either with symptoms attributable to the lower urinary tract or
      varying degrees of renal failure. Owing to the mild, non-specific initial
      symptoms and slow progression, presentation is delayed and patients are often
      lost to follow-up, only to present with advanced renal failure later on. We
      report a case of a young patient with pelvic lipomatosis who, after an initial
      diagnosis, was lost to follow-up for several years and then presented with
      uraemic encephalopathy. The case highlights the importance of regular follow-up
      and an early intervention before irreversible changes occur.

PMID- 11321860
TI  - Sumatriptin vs dihydroergotamine: patient preference.

PMID- 11321861
TI  - Co-trimoxazole and genital ulceration.

PMID- 11321862
TI  - Viagra: a three-year sexual revolution and the need to recognise its role within
      the NHS.

PMID- 11321863
TI  - Digoxin: a drug whose time has gone?

PMID- 11321864
TI  - Is a statin a statin?

PMID- 11321865
TI  - Rifampicin test in the diagnosis of Gilbert's syndrome.
AB  - Gilbert's syndrome (GS) is characterised by the existence of chronic mild
      unconjugated hyperbilirubinaemia. The value of rifampicin as a provocative test
      for the diagnosis of GS was evaluated and compared with a fasting test. Twenty
      two patients with GS, 15 patients with chronic liver disease and 20 healthy
      controls were included. Both rifampicin and fasting tests were applied to all
      subjects. In the fasting test, the subjects were given a 400 calorie/day diet for
      24 hours; in the rifampicin test, unconjugated bilirubin levels was measured
      before and four hours after taking 600 mg of rifampicin. Both tests achieved a
      significant increase in mean unconjugated bilirubin levels in patients with GS
      but not in the controls. The sensitivity and specificity of a rifampicin test in
      the diagnosis of GS were comparable with the fasting test. However, both tests
      caused a significant increase in unconjugated bilirubin levels in nearly half the
      patients with chronic liver disease. A rifampicin test may be used in the
      diagnosis of suspected GS instead of a fasting test, as it is simpler and more
      practical. However, its specificity for GS is not sufficient, because it also
      causes an increase in unconjugated bilirubin levels in some patients with chronic
      liver disease.

PMID- 11321866
TI  - The cost-effectiveness of doxazosin for the treatment of hypertension in type II
      diabetic patients in the UK and Italy.
AB  - The objective of this analysis was to assess the cost-effectiveness of achieving
      'tight control' versus 'less tight control' of blood pressure, as defined in the
      UK Prospective Diabetics Study 38, in type II diabetic patients in the UK and
      Italy. The effect of including doxazosin in a 'tight control' combination therapy
      was analysed. Given doxazosin's positive impact on lipid levels in addition to
      its antihypertensive effect, it is hypothesised that treatment including
      doxazosin will reduce the incidence of macrovascular complications. For each
      country, a Markov model was constructed to simulate macrovascular outcomes of
      patients on various drug combinations. Transitional probabilities were based on
      the risk rates presented in UKPDS 38. Risk rates were adjusted for the ageing of
      the cohort and the lipid-lowering properties of doxazosin using Framingham risk
      equations. Incremental cost-effectiveness ratios ranged from 2224 Pounds to 4867
      Pounds (US$3225-7057) per life-year saved for the UK and from L1.8-9.3 million
      (US$818-4159) per life-year saved for Italy. Doxazosin is a cost-effective agent
      when included in a combination therapy in the treatment of hypertension in the
      diabetic populations of the UK and Italy.

PMID- 11321867
TI  - Efficacy and safety of 'hot' tonsillectomy.
AB  - Recurrent acute tonsillitis, peritonsillar infections and quinsy (peritonsillar
      abscess) are common clinical conditions that present to a general practitioner.
      Management in general practice and in hospital is confounded by apparently
      conflicting treatment options in the medical literature. We have developed clear
      guidelines as part of an ongoing audit cycle which include performing quinsy or
      'hot' tonsillectomy in selected cases, alongside conservative treatments to
      ensure the speedy recovery and minimal hospitalisation of all patients, with
      resultant cost benefits.

PMID- 11321868
TI  - Lesser evaluated determinants of fistula formation in children with hypospadias.
AB  - Determinants of fistula formation, some of them not previously evaluated, were
      studied in 30 consecutive children admitted for hypospadias repair to our centre.
      All children were screened for any urinary or local infections. Vicryl and catgut
      were used alternately for reconstruction of the neo-urethra. Per urethral
      drainage was employed in all patients. The presence of unfavourable local
      anatomical factors, the surgeon's satisfaction at the end of the procedure and
      duration of surgery were noted. The patients were followed up for any
      urethrocutaneous fistula. Unsatisfactory surgery (chi-square = 6.53, p = 0.01),
      unfavourable anatomical factors (chi-square = 10.80, p = 0.001) and local
      infection (chi-square = 5.66, p = 0.017) had a strong association with fistula
      formation, whereas urine leakage and a history of previous surgery had only a
      marginal association. On application of stepwise binary logistic regression,
      unfavourable local anatomical factors (OR [95% CI]: 13.19 [1.20-143.50]) and
      urine leakage (OR [95% CI]: 14.35 [1.20-171.45]) emerge as strong risk factors
      for urethrocutaneous fistula, and local infection (OR [95% CI]: 8.70 (0.93
      81.01]) as a moderate risk factor.

PMID- 11321869
TI  - Nalidixic acid is still the drug of choice for shigellosis in Pakistan.

PMID- 11321870
TI  - Guidelines for antibiotic use.

PMID- 11321871
TI  - Integrated curriculum.

PMID- 11321872
TI  - An integrated curriculum for MBBS.
AB  - OBJECTIVE: To report the formulation and implementation of an organ system based
      integrated curriculum for MBBS students at Ziauddin Medical University (ZMU)
      Karachi. STEPS OF INTEGRATION: The Basic Medical Science Faculty (Anatomy,
      Physiology and Biochemistry) along with representatives from Medicine, Surgery
      and Community Health Sciences held joint meetings spread over weeks to design a
      system based integrated curriculum for the first two years of the MBBS class.
      Objectives of an integrated course were devised and the duties of term
      coordinator determined. CONCLUSION: Horizontal integration of Basic Science
      subjects can be achieved, with the subject specialists coordinating the teaching
      of a system based as opposed to subject based curriculum. The basic sciences can
      also be integrated with Community Health Sciences to achieve partial vertical
      integration.

PMID- 11321873
TI  - Vestibular schwannomas: clinical presentation, management and outcome.
AB  - OBJECTIVE: To review the demographic trends clinical spectrum, diagnosis,
      management and out come of patients with vestibular Schwannoma and to identify
      areas where improvements are needed. METHODS: All patients with vestibular
      schwannoma admitted to the Aga Khan University Hospital over the past 11 years
      were reviewed retrospectively. RESULTS: The age range of majority of 22 patients
      analyzed, was 41-50 years (23%). Hearing loss was the most common presenting
      symptom (96%). Other clinical features included cranial nerve palsies (59%) and
      headache (55%). Fifty percent had signs of raised intracranial pressure.
      Neuroimaging revealed "Stage IV b" (tumor distorting the brainstem and
      compressing the 4th ventricle) in 50% cases. Neurosurgical intervention was
      carried out in 86%; mainly using the retrosigmoid approach. Postoperative
      complications included facial nerve palsy in 13 (65%) and hydrocephalus in 5
      (25%) patients. Hearing determined clinically was preserved in three patients
      (14%). One patient died during the inpatient stay. CONCLUSION: Presentation of
      these patients is late and the outcome is poor.

PMID- 11321874
TI  - Induction of white cell proliferation due to haematopoietic growth factors is
      associated with an increase in multiple forms of dihydrofolate reductase in non
      neutropenic cancer patients.
AB  - OBJECTIVE: Granulocyte-colony stimulating factor (G-CSF) and granulocyte
      macrophage-colony stimulating factor (GM-CSF) are frequently used in cancer
      patients to overcome the granulocytopenic effects of chemotherapy, and also to
      mobilize the stem cells. The mobilized stem cells are collected from the
      peripheral blood and used for transplantation following high doses of
      chemotherapy. However, the molecular mechanism by which these colony stimulating
      factors (CSFs) bring about proliferation of myeloid precursor cells is not
      clearly known. Dihydrofolate reductase (DHFR), which has an established role in
      DNA synthesis, could be a link between administration of CSF and stem cell
      proliferation. The purpose of this study was to investigate whether CSFs induce
      white cell proliferation by producing multiple forms of DHFR. METHODS: Twelve
      patients with non-haematological malignancies were treated with either G-CSF or
      GM-CSF to mobilize stem cells. Nine healthy subjects were treated with placebo as
      controls. Blood samples were obtained before and after stimulation with CSFs or
      placebo. White blood cells were separated and concentrations of both active DHFR
      and immunoreactive nonfunctional form of DHFR were determined in their cytoplasm
      using methotrexate-binding assay and enzyme-linked immunosorbent assay,
      respectively. Total leucocytes count (TLC) was also monitored before and after
      stimulation with CSFs or placebo. RESULTS: There was a significant (P < 0.05)
      increase in concentration of immunoreactive nonfunctional form of DHFR and TLC
      following stimulation with CSFs. There was an increase in concentration of active
      DHFR as well, however, this did not reach statistical significance. In the
      placebo-treated subjects, no significant increase in active DHFR, immunoreactive
      nonfunctional form of enzyme or TLC was observed. However, it was noticed that
      the base-line values of active DHFR and immunoreactive nonfunctional form of
      enzyme in leucocytes of cancer patients were higher than the base-line values in
      leukocytes of normal healthy subjects. CONCLUSION: Our data suggest that colony
      stimulating factors induce white cell proliferation by increasing levels of
      multiple forms of DHFR.

PMID- 11321875
TI  - Hazard perception and occupational injuries in the welders and lathe machine
      operators of Rawalpindi and Islamabad.
AB  - OBJECTIVE: To study the prevalence of occupational injuries in the welders and
      lathe machine operators and their hazard perception. SETTING: This study was
      conducted in the welders and lathe machine operators working in the welding and
      metal working shops in Rawalpindi and Islamabad. METHODS: A cross-sectional
      survey was conducted by two trained health interviewers using uniform
      questionnaire with both close and open-ended questions. RESULTS: Two hundred and
      eight welders and 104 lathe machine operators were interviewed. Thirty nine
      (18.7%) welders and 27 (26%) lathe machine operators reported an injury in the
      past three months, while 63 (30.3%) welders and 76 (73.8%) lathe machine
      operators reported sustaining an injury in the past twelve months. However, only
      half of the welders and 31 (29.8%) lathe machine operators believed that their
      occupation was hazardous for health. CONCLUSION: For effective public health
      policy there is a need preventive education and enforcement of safety regulations
      for the informal occupational sector in Pakistan.

PMID- 11321876
TI  - Prescribing practices of consultants at Karachi, Pakistan.
AB  - OBJECTIVE: To audit the prescribing practices of consultants. DESIGN: A
      randomized sample survey of 354 consultants prescription for analysis of some
      basic parameters as recommended by World Health Organization (WHO). MAIN OUTCOME
      MEASURES: To provide feedback to the prescribers for promoting rational drug
      therapy. RESULTS: The average number of drugs for prescription were found to be
      4.51 and the average daily cost of prescribed drugs was Rs: 133.41. The
      antimicrobials, vitamins/minerals and injections were over-prescribed. About half
      of the prescribed drugs were from the National Essential Drugs List of Pakistan
      (NEDLP) and only a little over 12% were prescribed by their generic names.
      CONCLUSIONS: The prescribing practices of the consultants in Karachi are rather
      liberal and not rational. Overuse of antimicrobials and injections have been
      observed and there is general tendency of indulging in polypharmacy requiring
      continued medical education.

PMID- 11321877
TI  - Diabetic foot ulcer--a prospective study.
AB  - OBJECTIVE: To detect "Feet at Risk" early, its early diagnosis and treatment of
      foot ulceration to prevent amputation. SETTING AND METHOD: One hundred patients
      with diabetic foot problems were seen at Baqai Institute of Diabetology and
      Endocrinology from 06-01-97 to 14-04-99. Each Patient was examined for peripheral
      pulses, sensations and reflexes, for dryness of skin, deformity, callus and nail
      disorders and were photographed on first visit. RESULTS: There were 65% males and
      35% females included in this study. Ninety nine patients were type II diabetics,
      38% were either smokers or had other addictions (or were addicted to tobacco).
      Awareness about risk factors causing foot problems was lacking among all
      patients. Fifty percent patients were on oral hypoglycaemic agents, 48% were
      insulin treated, while 2% were on diet and exercise alone. Glycaemic control was
      poor in 70%, fair in 16% and was good in 14%, 31% were overweight and 5% patients
      were underweight. Duration of diabetes was greater than ten years in 58%, toes
      were affected in 44%, sole/metatarsal in 18%; rest included malleoli, heel etc.
      Eleven patients had ulcers on both feet. Neuropathic ulcer were 42%, neuro
      ischaemic 58%, Sixty nine percent patients were in the age group between 40-60
      years. Cause unknown 29% blisters and boil 14%, trauma/cutting 17%, burns 8%, dry
      skin/callus 10%. Fundal changes were present in 37%; proteinuria in 37%,
      ischaemic heart disease in 20%, hypertension 18%, In 60% more than one antibiotic
      was used. Foot ulcers of fifty nine patients healed on conservative management,
      six patients had below knee amputation, fifteen had toe amputation; nine were
      still on treatment, eleven lost contact. CONCLUSION: Lack of awareness, poor
      glycaemic control and duration of diabetes were the main factors causing diabetic
      foot problems. This study also confirmed that microvascular complications should
      be screened in patients with diabetic foot ulcers. Foot care education would be
      the most important way of dealing with this major problem.

PMID- 11321878
TI  - Management of hypertension and heart failure with AT1 receptor blockade.

PMID- 11321879
TI  - Adrenal myololipoma--a case report.

PMID- 11321880
TI  - Infantile fibromatosis presenting as a neck mass.

PMID- 11321881
TI  - Cholestasis with hepatic fibrosis secondary to sarcoidosis--a case report.

PMID- 11321882
TI  - Risk stratification after acute myocardial infarction.

PMID- 11321883
TI  - Perspective on variables in medical research.
AB  - Research concepts cannot be materialized until and unless study variables are
      carefully selected and clearly defined. However, emphasis on variables is not
      limited to data collection. It should be envisioned from the start that the
      contents of the variables recorded are congruent with the statistical analysis
      suggested. These two processes require a comprehensive understanding of variables
      in epidemiology and biostatistics disciplines. In this article classifications
      are discussed keeping in view their utility in medical research.

PMID- 11321884
TI  - Uropathogens and their susceptibility pattern: a retrospective analysis.
AB  - OBJECTIVE: To determine the frequency and antibiotic susceptibility pattern of
      uro-pathogens. SETTING: Department of Pathalogy, Ziauddin Medical Hospital
      Laboratory, Karachi. METHOD: A retrospective analysis was done on all the urine
      samples sent for culture and sensitivity during a seven months period. Two
      thousand eight hundred and forty four urine samples were received and inoculated
      in cysteine lactose electrolyte deficient agar (CLED). Positive samples were
      identified, processed and antibiotic susceptibility was carried out. Data was
      analyzed using Microsoft Excel 97. RESULTS: E. coli (45.6%) was the leading
      uropathogen followed by candida spp. (10.5%), enterococcus spp. (10.2%). For E.
      coli ampicillin, ceftazidime, nitrofurantoin and gentamycin sensitivity was 26%,
      20%, 79.5%, 65% respectively. Enterococcus isolates showed 60% resistance to
      ampicillin. CONCLUSION: The resistant pattern of uro-pathogens causing urinary
      tract infections to common antimicrobial agents is changing and must be taken
      into account when selecting treatment strategies. Therefore, antibiotic policy
      should be made according to local surveillance data.

PMID- 11321885
TI  - Management of resectable rectal cancer: an update.
AB  - Successful management of rectal cancer entails adequate assessment of patient
      related risk factors (co-morbid conditions, body habitus, anal sphincter
      function) and tumor characteristics (level, stage, and histo-morphologic
      features), and adequate knowledge of available diagnostic and therapeutic
      modalities. This report provides an update on sonographic assessment, operative
      management, neo-adjuvant therapy, and follow up of resectable potentially curable
      rectal cancer.

PMID- 11321886
TI  - Toxic epidermal necrolysis in a patient with severe aplastic anemia treated with
      cyclosporin A and G-CSF.
AB  - Toxic epidermal necrolysis (TEN) and severe aplastic anemia (SAA) are rare
      nonpredictable side effects of several drugs. To our knowledge there are no
      reports on the coexistence of these two disorders. This study presents a 23 year
      old man with TEN diagnosed 6 days after treatment with aminophenazone,
      paracetamol and phenoxymethylpenicillin. The resolution of the skin disorder was
      observed after few days of treatment with G-CSF and cyclosporin A. In contrast,
      SAA only partially responded to treatment with these agents.

PMID- 11321887
TI  - Surfactant protein D and KL-6 as serologic indicators of Pneumocystis carinii
      pneumonia in a child with acute lymphoblastic leukemia.
AB  - Pneumocystis carinii pneumonia (PCP) in immunocompromised patients is one of the
      important causes of morbidity and mortality. Serum levels of surfactant protein D
      (SP-D) and KL-6 are useful biomarkers for understanding some pulmonary
      inflammatory responses in patients with idiopathic pulmonary fibrosis (IPF). We
      present a child with PCP following bone marrow transplantation (BMT) for acute
      lymphoblastic leukemia (ALL), for whom both SP-D and KL-6 in sera were
      simultaneously measured through the clinical course of PCP. Both serum levels of
      SP-D and KL-6 were rapidly elevated reflecting some inflammatory processes in the
      lung that chest X-ray films and CT scans showed as ground-glass attenuations. He
      died due to respiratory failure 40 days after PCP developed. A combination of the
      assays for SP-D and KL-6 in sera may be helpful in predicting the treatment
      results for PCP.

PMID- 11321888
TI  - How to minimize missing those subjects with high 2HR plasma glucose but 'normal'
      fasting plasma glucose levels?
AB  - Among the subjects with 'normal' fasting plasma glucose (PG) levels (< 7.0
      mmol/L), some of them are actually suffering from impaired glucose tolerance and
      diabetes, which can only be diagnosed by 2hr PG levels. We aim to find out a
      proper clinical approach in order to minimize missing those subjects with high
      2hr PG but 'normal' fasting PG levels. We analyzed data collected from a
      previously published population-based prevalence survey for glucose intolerance
      in 1486 Hong Kong Chinese subjects who had no past history of diabetes. Of the
      1468 subjects, there were 138 subjects (9.4%) having "missed glucose
      intolerance". Compared to the diabetic subjects (fasting plasma glucose > or =
      7.0 mmol/L) after adjustment for age, the subjects with missed glucose
      intolerance had similar characteristics except lower glycemic level. Compared to
      the normal subjects (fasting plasma glucose < 7.0 mmol/L) after adjustment for
      age, subjects with missed glucose intolerance had more obesity (both general and
      central), more hypertension, worse glycemic status and lipid profile in both men
      and women. There were 38 subjects (2.6%) having impaired fasting glucose. Of
      these 38 subjects, 24 (63.2%) had missed glucose intolerance. The detection of
      missed glucose intolerance increased from 9.7% of overall male subjects to 23.1%
      in men with hypertension to 52.9% in men with both hypertension and family
      history of diabetes. Similarly, the detection of missed glucose intolerance
      increased from 9.0% of overall female subjects to 25.7% in women with obesity to
      45.2% in women with both obesity and hypertension. If only fasting plasma glucose
      is performed, 4% of subjects will be diagnosed to have diabetes or impaired
      fasting glucose while up to 10% of subjects having impaired glucose tolerance or
      diabetes will be missed in Hong Kong Chinese. The latter 2 groups of subjects
      have similar cardiovascular risk factors to those with fasting PG > or = 7.0
      mmol/L. We recommend that for those with a family history of diabetes,
      hypertension or obesity, an oral glucose tolerance test instead of fasting plasma
      glucose should be used in the first place for the diagnosis of glucose
      intolerance. For those with impaired fasting glucose, a routine follow-up oral
      glucose tolerance test should also be performed. This clinical approach may
      improve the detection of those subjects with glucose intolerance, who will be
      otherwise missed by using fasting plasma glucose alone.

PMID- 11321889
TI  - Muscle fiber composition and capillarization in relation to metabolic alterations
      in hypertensive men.
AB  - The aim of this study was to determine if there is a relationship among skeletal
      muscle fiber composition, capillarization, blood pressure (BP) and/or the
      components of the metabolic syndrome. Two groups were compared: 8 recently
      diagnosed, untreated, hypertensive men (BP > or = 140/90) and 7 normotensive men
      as controls. Muscle biopsies were taken from the vastus lateralis part of
      quadriceps femoris muscle in order to assess: fiber type proportion,
      capillarization, hexokinase, citrate synthase, beta-hydroxyacyl CoA dehydrogenase
      activities; lipoprotein lipase mass and activity, free fatty acids and
      triglycerides. Serum levels of insulin, glucose, cholesterol, uric acid and
      triglycerides were also assayed. Hypertensive patients had higher insulin levels
      and insulin resistance [homeostasis model assessment (HOMA)], a decreased
      hexokinase activity and an increase of muscle lipoprotein lipase mass as compared
      to controls. Interestingly, correlations among values differ in each group. The
      percentage of type IIB fibers was related to diastolic BP (blood pressure) in
      control and to mean BP in hypertensive subjects. Serum cholesterol and glucose
      were inversely related to the percentage of type I fibers in the control
      subjects. Negative correlations between capillarization and glucose, cholesterol
      and uric acid levels were found in control subjects. In all subjects, a strong
      correlation was found between SBP (systolic BP) and DBP (diastolic BP), and
      insulin resistance (IR) and uric acid levels. Muscle fiber type proportion and
      capillarization were related to blood pressure and components of the metabolic
      syndrome.

PMID- 11321890
TI  - The significance of platelet counts in coagulation studies.
AB  - Traditionally, the platelet count recommended for coagulation studies has been
      less than 10 x 10(9)/L, but the documentation for this is obscure. In the present
      study, platelet rich plasma (PRPs) and platelet poor plasmas (PPPs) were prepared
      from the same blood specimen to determine prothrombin times (PTs), International
      Normalized Ratios (INRs), partial thromboplastin times (PTTs), and their results
      compared. The measurements of all three of these parameters are not statistically
      or clinically significant in 100 paired comparisons. Incremented platelet count
      studies, selected by the number of platelets in the PRPs, showed that platelet
      counts of at least 199 x 10(9)/L, or perhaps even higher, did not compromise the
      results of PTs, INRs or PTTs. Such increased platelet counts, however, cannot be
      tolerated in the various studies for antiphospholipid antibodies, the Lupus
      Anticoagulant (LAC), or when monitoring heparin therapy with PTTs. Here, the < 10
      x 10(9)/L platelet levels must be respected; otherwise the tests would be
      compromised by platelet-liberated phospholipid (Triplett, Brand et al., 1983) or
      by Platelet Factor 4, respectively.

PMID- 11321891
TI  - Different effects of H. pylori water extracts on cytokines, pepsinogen C and
      gastrin mucosal release in patients with or without duodenal ulcer.
AB  - In the present study we ascertained whether cagA positive and negative H. pylori
      strains release water soluble products that can influence the production of
      gastric mucosal cytokines and endocrine (gastrin) or exocrine (pepsinogen C)
      secretion in 23 H. pylori positive and 19 H. pylori negative patients. Antral
      biopsies were obtained to classify inflammation, activity, atrophy, intestinal
      metaplasia and H. pylori density grade. The cagA gene was identified by means of
      the polymerase chain reaction (PCR) in H. pylori positive colonies after culture
      of mucosal samples. Three antral biopsies from each patient were incubated with
      (1.) Water extracts from cagA positive, (2.) Water extracts from cagA negative
      strains or (3.) H2O (control) at 37 degrees C in a CO2 incubator for 24 hrs.
      Gastrin, pepsinogen C, IL-1 beta, IL-8, GMCSF, and TNF alpha were measured in the
      supernatants and mucosal homogenates. H. pylori infection was significantly
      associated with an increased antral inflammation and activity (chi 2 = 21.7, p <
      0.001 and chi 2 = 42.0, p < 0.001), and increased mucosal levels of IL-1 beta, IL
      8 and TNF alpha. Water extracts from cagA positive strains enhanced the release
      of PGC in mucosal biopsy supernatants (p < 0.05) when patients were considered
      overall and the release of TNF alpha (p < 0.05) when only patients with duodenal
      ulcer were considered. Water extracts from cagA negative strains stimulated
      gastrin secretion (p < 0.05). None of the remaining cytokines were influenced by
      H. pylori water extracts. In conclusion, pepsinogen C and TNF alpha can be
      induced by cagA positive water extracts and may contribute to damage the gastric
      and duodenal mucosa. Our findings indicate that in patients with H. pylori
      infection the increase of the mucosal levels of IL-1 beta and IL-8 does not
      depend on H. pylori water soluble products, but probably depends on the entire
      bacterium.

PMID- 11321892
TI  - Reflections on 25 years of the International Journal of Group Psychotherapy.

PMID- 11321894
TI  - Commentary on my editorship (1980-1984).

PMID- 11321893
TI  - Commentary on my editorship (1970-1979).

PMID- 11321895
TI  - Commentary on my editorship (1985-1992).

PMID- 11321897
TI  - A retrospective of group therapy: a letter.

PMID- 11321896
TI  - Commentary on my editorship (1993-2001).

PMID- 11321898
TI  - An expectation of radical changes in the future of group psychotherapy.

PMID- 11321899
TI  - The future of group psychotherapy: expanding the conversation.

PMID- 11321900
TI  - Joining with resistance: addressing reluctance to engage in group therapy
      training.
AB  - Although research has documented the effectiveness of group psychotherapy,
      trainees are often reluctant to embrace this modality. This reluctance may
      reflect an informed choice based on knowledge, interest, and skill.
      Alternatively, reluctance may reflect misinformation or resistance due to
      conflicted feelings that arise from group dynamics. The latter are a major
      obstacle to the success of group therapy training and treatment programs.
      Understanding the origins of this reluctance and the developmental challenges of
      group therapy for trainees better equips supervisors to address this difficulty.
      This article uses case examples to illustrate how trainee reluctance emerges. It
      also provides strategies for working with hesitant trainees. The success of group
      therapy programs rests on the supervisor's ability to manage trainees'
      inhibitions to group therapy.

PMID- 11321901
TI  - The subjective experience of the self in the large group: two models for study.
AB  - More and more opportunities now exist for group therapists to engage in the study
      of the self in the large group at local, national, and international conferences
      as well as in clinical and other organizational settings. This may be
      particularly important for the group therapist in the next century with potential
      benefit not only for individuals but also for groups and social systems of all
      kinds. In this article, I review my own subjective experiences in the large group
      context and in large study group experiences. Then, I contrast the group analytic
      and the group relations approaches to the large group with particular reference
      to Winnicott's theory about maturational processes in a facilitating environment.

PMID- 11321902
TI  - The therapist's anxiety and resistance to group therapy.
AB  - When therapists contemplate starting groups, consider placing an individual
      patient within an existing group, or respond to the group reconfigurations when
      members are added or replaced, it raises their anxieties and resistances. Under
      these circumstances, the therapist must contend with many intersubjective
      factors: dread, fear, and idealization of groups; contagion and amplification of
      psychological phenomena; absorption in the group mentality; magnification of the
      therapist's centrality and importance; exposure and disturbance of existing
      relationships, and utilization of one's own emerging and evolving thoughts,
      feelings, and fantasies, along with the group's. Therapists learn about
      themselves and their groups by reviewing their countertransference, being alert
      to possible enactments, and listening to their patients, whose anxieties and
      resistances to group often reflect their own.

PMID- 11321903
TI  - A survey of mental health care provider's and managed care organization attitudes
      toward, familiarity with, and use of group interventions.
AB  - Managed Care has had a significant impact on delivery systems for mental health
      services. Direct and indirect persuasion to provide more cost-effective
      treatments has been one consequence. The cost-saving qualities and the
      effectiveness of group interventions have produced clear expectations for an
      increased use of therapy groups. This study compared perceptions and uses of
      group treatments on a national sample of managed care organizations and mental
      health providers. Because group psychotherapy encompasses such a broad
      definition, five specific types of group interventions were defined: problem
      focused homogenous, process-oriented heterogeneous, psycho-educational, self
      help, and short-term groups. Implications of differences and similarities between
      directors of managed care organizations and treatment providers are examined and
      discussed across five response categories (familiarity/training, perceived
      effectiveness, likelihood of reimbursement/referral, daily use, and expectation
      for future use).

PMID- 11321904
TI  - Harnessing the power of the group for latency-aged sexual abuse victims.
AB  - For children who have been sexually abused, group therapy is often a preferred
      treatment modality. Although much consideration has been given to what structured
      activities, goals, and objectives should be included in groups for sexually
      abused children, limited attention has been paid to the dynamics and processes
      inherent in the group. This article follows the dynamic unfolding of a short-term
      structured group for latency-aged, female sexual abuse victims. Special emphasis
      is placed on listening to the messages underlying children's actions and
      responding to the message rather than suppressing or limiting the behavior. It is
      argued that by attending to group dynamics and processes in a theme-focused
      group, structured activities become more effective and the power of the group can
      be harnessed to foster opportunities for healing that otherwise might go
      unrecognized.

PMID- 11321905
TI  - Investigation of polychlorinated biphenyl removal from contaminated soil using
      microwave-generated steam.
AB  - A feasibility study of polychlorinated biphenyl (PCB) removal from contaminated
      soils using microwave-generated steam (MGS) was performed. Initial experimental
      results show that MGS effectively removed PCBs from contaminated soil with an
      overall removal efficiency of greater than 98% at a steam-to-soil mass ratio of
      3:1. Removal efficiency was found to be dependent upon the amount of steam
      employed, expressed as a mass ratio of steam applied to soil mass. Evaporation
      was identified as a major mechanism in removing PCBs from the soil. Rapid
      expansion and evaporation of pore water by microwave dielectric heating
      accelerated evaporation rates of PCB molecules. Increased solubility of PCBs into
      the heated aqueous phase is also hypothesized. Together these effects increase
      mass-transfer rates, thus enhancing removal of PCBs from the soil.

PMID- 11321906
TI  - Determination of source contributions to ambient PM2.5 in Kaohsiung, Taiwan,
      using a receptor model.
AB  - Ambient particulates of PM2.5 were sampled at three sites in Kaohsiung, Taiwan,
      during February and March 1999. In addition, resuspended PM2.5 collected from
      traffic tunnels, paved roads, fly ash of a municipal solid waste (MSW)
      incinerator, and seawater was obtained. All the samples were analyzed for twenty
      constituents, including water-soluble ions, organic carbon (OC), elemental carbon
      (EC), and metallic elements. In conjunction with local source profiles and the
      source profiles in the model library SPECIATE EPA, the receptor model based on
      chemical mass balance (CMB) was then applied to determine the source
      contributions to ambient PM2.5. The mean concentration of ambient PM2.5 was 42.69
      53.68 micrograms/m3 for the sampling period. The abundant species in ambient
      PM2.5 in the mass fraction for three sites were OC (12.7-14.2%), SO4(2-) (12.8
      15.1%), NO3- (8.1-10.3%), NH4+ (6.7-7.5%), and EC (5.3-8.5%). Results of CMB
      modeling show that major pollution sources for ambient PM2.5 are traffic exhaust
      (18-54%), secondary aerosols (30-41% from SO4(2-) and NO3-), and outdoor burning
      of agriculture wastes (13-17%).

PMID- 11321907
TI  - Identification of selected hormonally active agents and animal mammary
      carcinogens in commercial and residential air and dust samples.
AB  - In order to characterize typical indoor exposures to chemicals of interest for
      research on breast cancer and other hormonally mediated health outcomes, methods
      were developed to analyze air and dust for target compounds that have been
      identified as animal mammary carcinogens or hormonally active agents and that are
      used in commercial or consumer products or building materials. These methods were
      applied to a small number of residential and commercial environments to begin to
      characterize the extent of exposure to these classes of compounds. Phenolic
      compounds, including nonylphenol, octylphenol, bisphenol A, and the methoxychlor
      metabolite 2,2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane (HPTE), were extracted,
      derivatized, and analyzed by gas chromatography/mass spectrometry (GC/MS)
      selective ion monitoring (SIM). Selected phthalates, pesticides, polycyclic
      aromatic hydrocarbons (PAHs), and polychlorinated biphenyls (PCBs) were extracted
      and analyzed by GC/MS-SIM. Residential and workplace samples showed detectable
      levels of twelve pesticides in dust and seven in air samples. Phthalates were
      abundant in dust (0.3-524 micrograms/g) and air (0.005-2.8 micrograms/m3).
      Nonylphenol and its mono- and di-ethoxylates were prevalent in dust (0.82-14
      micrograms/g) along with estrogenic phenols such as bisphenol A and o-phenyl
      phenol. In this 7-sample pilot study, 33 of 86 target compounds were detected in
      dust, and 24 of 57 target compounds were detected in air. In a single sample from
      one home, 27 of the target compounds were detected in dust and 15 in air,
      providing an indication of chemical mixtures to which humans are typically
      exposed.

PMID- 11321908
TI  - Development and evaluation of an impactor for a PM2.5 speciation sampler.
AB  - A conventional impactor for a particle speciation sampler was developed and
      validated through laboratory and field tests. The speciation sampler consists of
      the following components: a PM2.5 conventional impactor that removes particles
      larger than 2.5 microns, an all-glass, coated honeycomb diffusion denuder, and a
      47-mm filter pack. The speciation sampler can operate at two different sampling
      rates: 10 and 16.7 L/min. An experimental characterization of the impactor's
      performance was conducted. The impactor's collection efficiency was examined as a
      function of critical design parameters such as Reynolds number, the distance from
      the nozzle exit to the impaction plate, and the impaction substrate coating
      method. The bounce of particles larger than the cut point was successfully
      minimized by using a greased surface as the impaction substrate. Additionally, a
      series of field intercomparison experiments were conducted at both 10 and 16.7
      L/min airflow. PM2.5 mass and SO4(2-) concentrations were measured and compared
      with the Federal Reference Method (FRM) and found to be in good agreement.
      Results of the laboratory chamber tests also indicated that the impactor's
      performance was in good agreement with the FRM.

PMID- 11321909
TI  - Boiler briquette coal versus raw coal: Part I--Stack gas emissions.
AB  - Stack gas emissions were characterized for a steam-generating boiler commonly
      used in China. The boiler was tested when fired with a newly formulated boiler
      briquette coal (BB-coal) and when fired with conventional raw coal (R-coal). The
      stack gas emissions were analyzed to determine emission rates and emission
      factors and to develop chemical source profiles. A dilution source sampling
      system was used to collect PM on both Teflon membrane filters and quartz fiber
      filters. The Teflon filters were analyzed gravimetrically for PM10 and PM2.5 mass
      concentrations and by X-ray fluorescence (XRF) for trace elements. The quartz
      fiber filters were analyzed for organic carbon (OC) and elemental carbon (EC)
      using a thermal/optical reflectance technique. Sulfur dioxide was measured using
      the standard wet chemistry method. Carbon monoxide was measured using an Orsat
      combustion analyzer. The emission rates of the R-coal combustion (in kg/hr),
      determined using the measured stack gas concentrations and the stack gas emission
      rates, were 0.74 for PM10, 0.38 for PM2.5, 20.7 for SO2, and 6.8 for CO, while
      those of the BB-coal combustion were 0.95 for PM10, 0.30 for PM2.5, 7.5 for SO2,
      and 5.3 for CO. The fuel-mass-based emission factors (in g/kg) of the R-coal,
      determined using the emission rates and the fuel burn rates, were 1.68 for PM10,
      0.87 for PM2.5, 46.7 for SO2, and 15 for CO, while those of the BB-coal were 2.51
      for PM10, 0.79 for PM2.5, 19.9 for SO2, and 14 for CO. The task-based emission
      factors (in g/ton steam generated) of the R-coal, determined using the fuel-mass
      based emission factors and the coal/steam conversion factors, were 0.23 for PM10,
      0.12 for PM2.5, 6.4 for SO2, and 2.0 for CO, while those of the BB-coal were 0.30
      for PM10, 0.094 for PM2.5, 2.4 for SO2, and 1.7 for CO. PM10 and PM2.5 elemental
      compositions are also presented for both types of coal tested in the study.

PMID- 11321910
TI  - Boiler briquette coal versus raw coal: Part II--Energy, greenhouse gas, and air
      quality implications.
AB  - The objective of this paper is to conduct an integrated analysis of the energy,
      greenhouse gas, and air quality impacts of a new type of boiler briquette coal
      (BB-coal) in contrast to those of the raw coal from which the BB-coal was
      formulated (R-coal). The analysis is based on the source emissions data and other
      relevant data collected in the present study and employs approaches including the
      construction of carbon, energy, and sulfur balances. The results show that
      replacing R-coal with BB-coal as the fuel for boilers such as the one tested
      would have multiple benefits, including a 37% increase in boiler thermal
      efficiency, a 25% reduction in fuel demand, a 26% reduction in CO2 emission, a
      17% reduction in CO emission, a 63% reduction in SO2 emission, a 97% reduction in
      fly ash and fly ash carbon emission, a 22% reduction in PM2.5 mass emission, and
      a 30% reduction in total emission of five toxic hazardous air pollutant (HAP)
      metals contained in PM10. These benefits can be achieved with no changes in
      boiler hardware and with a relatively small amount of tradeoffs: a 30% increase
      in PM10 mass emission and a 9-16% increase in fuel cost.

PMID- 11321911
TI  - Incineration of paper sludge in a prototype vortexing fluidized bed combustor.
AB  - All experiments were carried out in a prototype vortexing fluidized bed combustor
      (VFBC). The dimension of the combustion chamber is 0.7 x 1.4 x 2 m, and the
      freeboard section is 1 m i.d. and 4 m in height. Paper sludge was used as the
      feeding material. Two types of coal particles were employed as the supplementary
      fuel. In order to understand the characteristics of the VFBC system for paper
      sludge incineration, the effect of various operating parameters, such as the
      primary airflow, excess air ratio, and secondary airflow rates, on temperature
      distribution, ash elutriation, combustion efficiency, and pollutant emissions
      were investigated.

PMID- 11321912
TI  - Chemical characterization of emissions from vegetable oil processing and their
      contribution to aerosol mass using the organic molecular markers approach.
AB  - The organic fraction of aerosol emitted from a vegetable oil processing plant was
      studied to investigate the contribution of emissions to ambient particles in the
      surrounding area. Solvent-soluble particulate organic compounds emitted from the
      plant accounted for 10% of total suspended particles. This percentage was lower
      in the receptor sites (less than 6% of total aerosol mass). Nonpolar, moderate
      polar, polar, and acidic compounds were detected in both emitted and ambient
      aerosol samples. The processing and combustion of olive pits yielded a source
      with strong biogenic characteristics, such as the high values of the carbon
      preference index (CPI) for all compound classes. Polycyclic aromatic hydrocarbons
      (PAHs) detected in emissions were associated with both olive pits and diesel
      combustion. The chromatographic profile of dimethylphenanthrenes (DMPs) was
      characteristic of olive pit combustion. Organic aerosols collected in two
      receptor sites provided a different pattern. The significant contribution of
      vehicular emissions was identified by CPI values (approximately 1) of n-alkanes
      and the presence of the unresolved complex mixture (UCM). In addition, PAH
      concentration diagnostic ratios indicated that emissions from catalyst and
      noncatalyst automobiles and heavy trucks were significant. The strong even-to-odd
      predominance of n-alkanols, n-alkanoic acids, and their salts indicated the
      contribution of a source with biogenic characteristics. However, the profile of
      DMPs at receptor sites was similar to that observed for diesel particulates.
      These differences indicated that the contribution of vegetable oil processing
      emissions to the atmosphere was negligible.

PMID- 11321913
TI  - Abatement of ammonia and hydrogen sulfide emissions from a swine lagoon using a
      polymer biocover.
AB  - The purpose of this research was to determine the efficiency of a polymer
      biocover for the abatement of H2S and NH3 emissions from an east-central Missouri
      swine lagoon with a total surface area of 7800 m2. The flux rate of NH3, H2S, and
      CH4 was monitored continuously from two adjacent, circular (d = 66 m) control and
      treatment plots using a nonintrusive, micrometeorological method during three
      independent sampling periods that ranged between 52 and 149 hr. Abatement rates
      were observed to undergo a temporal acclimation event in which NH3 abatement
      efficiency improved from 17 to 54% (p = < 0.0001 to 0.0005) and H2S abatement
      efficiency improved from 23 to 58% (p < 0.0001) over a 3-month period. The
      increase in abatement efficiency for NH3 and H2S over the sampling period was
      correlated with the development of a stable anaerobic floc layer on the bottom
      surface of the biocover that reduced mass transfer of NH3 and H2S across the
      surface. Analysis of methanogenesis activity showed that the biocover enhanced
      the rate of anaerobic digestion by 25% when compared with the control. The
      biocover-enhanced anaerobic digestion process was shown to represent an effective
      mechanism to counteract the accumulation of methanogenic substrates in the
      biocovered lagoon.

PMID- 11321914
TI  - The kinetics of catalytic incineration of dimethyl sulfide and dimethyl disulfide
      over an MnO/Fe2O3 catalyst.
AB  - The catalytic incineration of dimethyl sulfide and dimethyl disulfide [(CH3)2S
      and (CH3)2S2] over an MnO/Fe2O3 catalyst was carried out in a bench-scale
      catalytic incinerator. Three kinetic models (i.e., the power-rate law, the Mars
      and Van Krevelen model, and the Langmuir-Hinshelwood model) were used to analyze
      the results. A differential reactor design was used for best fit of kinetic
      models in this study. The results show that the Langmuir-Hinshelwood model may be
      feasible to describe the catalytic incineration of (CH3)2S and (CH3)2S2. This
      suggests that the chemical adsorption of O2 molecules is important in this
      incineration.

PMID- 11321915
TI  - A tracer study of headspace ventilation in a collector sewer.
AB  - A field-scale tracer test was conducted to evaluate in-situ ventilation rates in
      a major collector sewer. The sewer under study was approximately 11 km long and
      ranged from 0.61 to 2.1 m in diameter. For the purposes of the tracer testing,
      the collector was divided into four reaches, each of which was tested
      individually. The tracer test involved injecting a measured volume of CO gas into
      a manhole over a short time period. CO concentrations were then measured in the
      collector headspace at selected manholes along the length of the reach. The
      technique employed successfully measured average headspace velocities over
      extended lengths of the collector. In a section that had a relatively stagnant
      headspace, approximately 1.1 km of sewer could be evaluated, with substantial
      tracer loss attributed to losses to manholes. In a section of the sewer with
      elevated headspace velocities, a section approximately 7.0 km long was
      successfully tested with one injection of tracer gas. The velocities observed in
      the collector varied substantially with time and location in the collector. The
      lowest velocities measured were in the upstream sections, with a minimum observed
      value of 3.8 m/min. The highest velocities were observed in the downstream
      sections, with a maximum value of 31.5 m/min. The presence of a substantial drop
      structure appeared to reduce the headspace velocity in the upstream reach. In
      general, there was an increasing trend in gas-phase flows with distance along the
      length of the collector. Flows at the discharge end of the collector were almost
      2 orders of magnitude greater than those at the beginning.

PMID- 11321916
TI  - Black carbon aerosol at McMurdo Station, Antarctica.
AB  - Aerosol light absorption as black carbon (BC) was measured from November 19,
      1995, to February 6, 1996, at a location 0.65 km downwind of the center of
      McMurdo Station on the Antarctic coast. The results show a bimodal frequency
      distribution of BC concentrations. Approximately 65% of the measurements were
      found in a mode at a low range of concentrations centered at approximately 20
      ng/m3. These concentrations are higher than those found at other remote Antarctic
      locations and probably represent contamination from the station. The remaining
      measurements were in a high-concentration mode (BC approximately 300 ng/m3),
      indicating direct impact of local emissions from combustion activities at the
      station. High values of BC were associated with winds from the direction of the
      station, and the BC flux showed a clear directionality. Maximum BC concentrations
      occurred between 7:00 and 11:00 a.m. The "polluted" mode accounted for more than
      80% of the BC frequency-weighted impact at this location.

PMID- 11321917
TI  - Time-series analysis of above-road particulate matter at the Caldecott Tunnel
      exit.
AB  - On November 18, 1997, above-road particulate matter (PM) lidar (light detection
      and ranging) signals and heavy-duty (HD) and light-duty (LD) vehicle counts were
      simultaneously collected for 894 10-sec sampling periods at the Caldecott Tunnel
      in Orinda, CA, for the purpose of measuring the relative contributions of LD and
      HD vehicles to the PM lidar signal under real-world driving conditions. The
      relationship between the PM lidar signal and traffic activity (i.e., LD and HD
      traffic volumes) was examined using a time-series analysis technique, multilagged
      regression. The time-series model results indicate that the PM lidar signal in
      the current sampling period (PMt) depended on the level recorded in the previous
      three sampling periods (i.e., PMt-1, PMt-2, and PMt-3), the number of LD vehicles
      in the seventh past sampling period (LDt-7), and the number of HD vehicles
      measured 80 sec previous to the current sampling period (HDt-8). On a 10-sec
      period basis, the model results indicate that HD vehicles contributed, on
      average, 3 times more to above-road PM lidar signals than did LD vehicles. The
      observed lag in the relationship between vehicle types and the lidar signal 20 m
      above the road suggests that resuspended road dust, rather than tailpipe exhaust
      emissions, was the main source of the detected PM. Detection of road dust at such
      heights above the road suggests the need for investigating the processes
      governing the vertical transport and recycling of PM over the road as a function
      of vehicle dynamics under a range of meteorological conditions.

PMID- 11321918
TI  - Dissociation of sulfur hexafluoride tracer gas in the presence of an indoor
      combustion source.
AB  - As an odorless, nontoxic, and inert compound, sulfur hexafluoride (SF6) is one of
      the most widely used tracer gases in indoor air quality studies in both
      controlled and uncontrolled environments. This compound may be subject to
      reactions with water vapor under elevated temperature to form acidic inorganic
      compounds such as HF and H2SO4. Thus, in the presence of unvented combustion
      sources such as kerosene heaters, natural gas heaters, gas log fireplaces,
      candles, and lamps, the SF6 dissociation may interfere with measurements of the
      emissions from these sources. Tests were conducted in a research house with a
      vent-free natural gas heater to investigate these potential interferences. It was
      observed that the heater operation caused about a 5% reduction of SF6
      concentration, which can be an error source for the ventilation rate measurement
      and consequently the estimated pollutant emission rates. Further analysis
      indicates that this error can be much greater than the observed 5% under certain
      test conditions because it is a function of the ventilation flow rate. Reducing
      the tracer gas concentration has no effect on this error. A simple theoretical
      model is proposed to estimate the magnitude of this error. The second type of
      interference comes from the primary and secondary products of the SF6
      dissociation, mainly H2SO4, SO2, HF, and fine particulate matter (PM). In the
      presence of approximately 5 ppm SF6, the total airborne concentrations of these
      species increased by a factor of 4-10. The tests were performed at relatively
      high SF6 concentrations, which is necessary to determine the interferences
      quantitatively. The second type of interference can be significantly reduced if
      the SF6 concentration is kept at a low ppb level.

PMID- 11321919
TI  - First, the bad news. Even PMH sale may not keep its hospital open.

PMID- 11321920
TI  - Doors are open, but no one's home. Demographic shift, not mismanagement, shuts
      S.C. CareAlliance hospital.

PMID- 11321921
TI  - An amicable breakup. Milwaukee system ends operations, but some of its hospitals
      stay together.

PMID- 11321922
TI  - Shrinking the 'quality gap'. Catholic Health Initiatives is first major system to
      earn national award.

PMID- 11321923
TI  - Reviving ailing hospitals. Turnaround specialists offer antidote to chronic
      factors afflicting industry.

PMID- 11321924
TI  - City of brotherly competition. Healthcare-intensive Philadelphia market operates
      on razor-thin margins.

PMID- 11321925
TI  - Philly hospital thrives thanks to doc ties.

PMID- 11321926
TI  - Hopping mad. Medicare HMOs' restrictions on drug coverage prompt high enrollee
      turnover.

PMID- 11321927
TI  - Change in plans. Rapidly deteriorating conditions force Iasis to cancel trip to
      IPO market.

PMID- 11321928
TI  - DMC buys back HMO. No-cash trade with OmniCare to keep hospital atop 'healthcare
      food chain'.

PMID- 11321929
TI  - Scully gets started at HCFA. But administrator-designate keeps stock and board
      seats-for now.

PMID- 11321930
TI  - Classification of diabetes mellitus.
AB  - Diabetes mellitus affects almost 16 million Americans. It has become a major
      public health problem and the number one cause of adult blindness, end-stage
      renal disease, and nontraumatic amputations in the United States. It also
      markedly increases the risk for cardiovascular, cerebrovascular, and peripheral
      artery disease. The resultant increased morbidity and mortality results in a cost
      from diabetes of almost $100 billion annually in the United States. Studies like
      the UK Prospective Diabetes Study have noted that a substantial percentage of
      patients with newly diagnosed diabetes already have evidence of microvascular and
      macrovascular complications of the disease. This indicates that diabetes began in
      these individuals many years before it was diagnosed. By reducing the diagnostic
      glycemic threshold for diabetes and recommending regular screening of individuals
      at increased risk, the ADA hopes that patients will have diabetes diagnosed
      earlier, before the occurrence of complications and at a time when appropriate
      treatment can reduce the long-term complications, adverse clinical outcomes, and
      impaired quality of life that today afflict so many diabetic individuals.

PMID- 11321931
TI  - Diabetic nephropathy.
AB  - Diabetic nephropathy is the leading cause of end-stage renal disease in the
      United States and the largest contributor to the total cost of diabetic care. In
      addition to the development of diabetic nephropathy and end-stage renal failure,
      diabetic patients with evidence of albuminuria have a much higher risk of
      developing myocardial infarctions, cerebrovascular accidents, severe progressive
      retinopathy, and neuropathy. This article characterizes the clinical and
      pathologic features of diabetic nephropathy and reviews the major pathogenetic
      theories that underlie the development of this dreaded complication of diabetes.
      Widespread screening for this condition and aggressive treatment of diabetic
      nephropathy at early stages of disease are critical to diminish the risk of
      costly late complications.

PMID- 11321932
TI  - Lipid disorders in type 1 and type 2 diabetes.
AB  - Atherosclerotic cardiovascular disease is the most important cause of morbidity
      and mortality in diabetic subjects. Abnormalities in circulating lipids and
      lipoproteins are considered to be important risk factors for cardiovascular
      disease because they occur with increased frequency in diabetic individuals.
      Because reversal of these abnormalities carries the potential for preventing or
      ameliorating cardiovascular disease, their identification and management with
      other cardiovascular disease risk factors deserve equal importance to the
      management of hyperglycemia and frequently are complementary to it.

PMID- 11321933
TI  - Immunopathology of immune-mediated (type 1) diabetes.
AB  - Immune-mediated diabetes is established as an autoimmune disease, which most
      often is induced during late infancy or early childhood. Multiple genetic lesions
      in immune tolerance are required before autoimmunity can be sustained once
      induced by environmental agents, such as viruses. The diagnostic hallmarks of the
      disease are the islet autoantibodies, which should be made routinely available to
      physicians to distinguish this disease from other forms of diabetes. The ability
      to identify individuals with impending IMD and those at high risk of IMD lends
      itself to the development of clinical trials to prevent diabetes by immunologic
      means. We believe that this will soon be possible with the development and use of
      vaccines.

PMID- 11321934
TI  - Gestational diabetes mellitus.
AB  - In summary, much controversy exists surrounding the diagnosis, treatment, and
      even existence of GDM. At present, there is not enough evidence to advocate the
      Carpenter and Coustan criteria over the NDDG criteria. In univariate analysis,
      the Toronto Tri-Hospital Study demonstrated an increased incidence of cesarean
      section, macrosomia, and preeclampsia with increasing carbohydrate intolerance in
      those who did not meet NDDG criteria for GDM. Multivariate analysis, however,
      showed that this contribution is small relative to other nonmodifiable risk
      factors. A shift to the Carpenter and Coustan criteria would identify a larger
      population of patients with GDM and increase treatment costs. In addition,
      although treatment of these borderline GDM patients might reduce macrosomia,
      there is no evidence to indicate that it reduces the cesarean section rate. The
      precise threshold at which glucose intolerance adversely affects pregnancy
      outcomes and increases the risk for the development of type 2 diabetes in the
      mother is unknown. The perinatal risks associated with hyperglycemia seem to
      increase continuously with increasing maternal hyperglycemia. More randomized
      intervention trials are needed to define the effects of graded increases in
      glucose intolerance on maternal and fetal morbidity.

PMID- 11321935
TI  - Liver disease and diabetes mellitus.
AB  - The liver plays an important role in the pathogenesis of NIDDM. More importantly
      to the clinician is the myriad of situations in which the care of the patient
      with diabetes is affected by or causes an effect to the liver. Patients with
      underlying diabetes can present with abnormal liver chemistries, which can
      represent findings as benign as hepatic steatosis or as severe as cirrhosis of
      the liver. The medications used to treat diabetes can be potent hepatotoxins.
      Several primary liver diseases are associated with increased risk of the
      development of diabetes. Epidemiologically, there seems to be a correlation
      between diabetes mellitus, the most common endocrinologic disease, and hepatitis
      C, the leading cause of chronic liver disease in the United States. In the
      management of end-stage liver disease, both cirrhosis and orthotopic liver
      transplantation promote glucose intolerance and diabetes in a number of patients
      through various mechanisms including insulin resistance and impaired insulin
      secretion. These relationships highlight both the importance of the liver as an
      endocrine organ and the multisystem aspects of the patient with diabetes
      mellitus.

PMID- 11321936
TI  - Clinical features of insulin resistance and beta cell dysfunction and the
      relationship to type 2 diabetes.
AB  - Type 2 diabetes mellitus is a heterogeneous disorder characterized by varying
      degrees of impaired insulin secretion and insulin resistance.  The metabolic
      manifestations of insulin resistance include (1) reduced insulin-stimulated
      glucose uptake, (2) reduced insulin-suppression of  endogenous glucose
      production, and (3) reduced antilipolysis.  All of these mechanisms contribute to
      the hyperglycemis of T2DM, both post-absorptively and postprandially.  In
      addition, insulin resistance is involved in decreaswed insulin-induced
      vasodilation, dyslipidemia, and platelet hyperaggregability.  The pathogenesis of
      T2DM involves a combination of genetic and environmental factors.  Monogenic
      causes account for only a minority of insulin resistance and beta cell
      dysfunction. Among environmental factors the most important are obesity, reduced
      physical activity, and age.  Obesity-associated insulin resistance is thought to
      be mediated mainly by FFAs whose clearance is reduced in subjects with T2DM.  A
      number of clinical tests have been developed to assess insulin sensitivity and
      beta cell function in vivo.  The euglycemic hyperinsulinemic clamp and the
      hyperglycemic clamp, respectively, represent the gold standard procedures. 
      Recently, indices calculated parameters of the OGTT have been proposed as
      surrogates for assessing both insulin sensitivity and beta cell function in
      clinical situations and epidemiologic studies.

PMID- 11321937
TI  - Glycated proteins in diabetes.
AB  - The term nonenzymatic glycation (of protein) refers to a wide variety of
      spontaneous reactions between reducing sugars and protein-bound amines. This
      reaction has been documented in humans and plays a role in the development of
      diabetic complications and perhaps in some of the degenerative processes of
      aging. In addition to the monocarbonyl sugars and their derivatives, an
      additional source of glycation is alpha-dicarbonyls. Over time, nonenzymatic
      glycation leads to the formation of irreversible terminal products known
      collectively as advanced glycation end-products (AGE) and extensive data on the
      role of AGEs in the etiology of diabetic complications exist. Our improved
      ability to measure alpha-dicarbonyls and specific AGEs may provide new and more
      powerful tools to monitor diabetes and predict diabetic complications in the
      future.

PMID- 11321938
TI  - Hypoglycemic disorders.
AB  - Hypoglycemia occurs as an epiphenomenon in many serious diseases and further
      investigation may be unnecessary. In other, often seemingly healthy individuals,
      it is responsible for their presenting symptoms. In them preliminary diagnosis
      depends on demonstrating a low blood glucose concentration during spontaneous
      symptoms by ambulatory self-collection of capillary blood and its analysis for
      glucose in the laboratory. Subsequent investigation requires appropriate plasma
      hormone analysis on blood collected while the patient is hypoglycemic.

PMID- 11321939
TI  - Uncontrolled diabetes mellitus.
AB  - The conditions of DKA and NKH are life-threatening complications of poorly
      controlled diabetes mellitus. They have characteristic clinical and laboratory
      features. If not treated appropriately, they can result in a high mortality rate
      of 15% to 28% in DKA and 17% to 50% in NKH.

PMID- 11321940
TI  - [Study on the awareness, treatment and control of hypertension in Qingdao rural
      residents].
AB  - In order to study the awareness, treatment and control rates and the risk factors
      of hypertension in Qingdao rural residents, a cluster random sampling method was
      used. Blood pressure measurement and questionnaire regarding risk factors for
      hypertension were applied to 3700 residents aged over 18. The standardized
      prevalence of hypertension in selected Qingdao rural residents was 19.5%. The
      awareness rate of hypertension was 31.5%. The main factors affecting awareness
      included age, cultural level, family income, family history of hypertension, and
      knowing the criteria for normal blood pressure (BP). The rate of taking regular
      treatment for hypertension was 35.7%. The factors affecting treatment for
      hypertension were age, culture level, times of measuring blood pressure (BP),
      suffering from complications of hypertension and family income. The awareness,
      treatment and control of hypertension should be improved and a comprehensive
      measure should be taken to prevent hypertension in Qingdao rural residents.

PMID- 11321941
TI  - [Effect of lead exposure in prenatal and postnatal duration on infant growth].
AB  - The blood lead (PbB) levels of pregnant women and their babies were followed up
      since the third month of pregnancy until their babies were 2 years old. The
      general condition of delivery, family history of the pregnant women, feeding and
      development of infants were investigated. Prenatal and postnatal PbB levels and
      their effects on infant growth were analysed. The result showed a significant
      negative correlation of PbB level of pregnant women near delivery, and in
      umbilical cord with the growth of infants. Multiple regression analysis showed a
      negative correlation between PbB level and height, weight of infant at 1 and 2
      years old.

PMID- 11321942
TI  - [Fasting insulin level and hypertensive family history in overweighted children].
AB  - In order to analyze the relationship between fasting insulin level and body mess
      index (BMI), blood pressure and lipids, and to discuss the effect of hypertensive
      family history, 317 healthy children aged 8-11 years including 74 overweighted
      and 243 non-overweighted were selected randomly from 4 primary schools in
      Beijing. Anthropometry, fasting insulin and lipids were measured, and the family
      history of hypertension (FHH) was recorded. After adjusting of age and sex, the
      levels of blood fasting insulin, cholesterol and triglyceride were significantly
      higher (P < 0.01) and the ratio of HDL/LDL and apoA/apoB were significantly lower
      (P < 0.01) in the overweighted than that in non-overweighted children. After
      controlling BMI, the partial correlation coefficients between fasting insulin and
      TG, systolic pressure was 0.20 (P < 0.01) and 0.12 (P < 0.01) respectively.
      Moreover, among the overweighted children, but not among non-overweighted
      children, those with FHH had a significantly higher fasting insulin than those
      without FHH (P < 0.01). It is concluded that hypertensive family history may play
      an important role in contributing to the higher level of serum insulin of
      overweighted children, and higher serum insulin may concerted with some metabolic
      disorders in overweighted children.

PMID- 11321943
TI  - [Dietary intake of antioxidant vitamins and personal demographic characteristics
      of Guangdong residents].
AB  - The study aim at revealing the associations between the intake of dietary
      antioxidant vitamins and personal characteristics on age, sex, education, working
      status and household gross income etc. The intake of antioxidant vitamins in a
      population of Guangdong Province was studied. A total of 418 males and 503
      females, aged 25-84 year were interviewed, and questionnaires on socio-demography
      and on a 12-month food intake frequency (FFQ) were completed in 1995. The daily
      average intake of antioxidant vitamins and energy was higher in male than in
      female. Older subjects consumed lesser antioxidant vitamins. The vitamin E intake
      of higher education persons as well as high family income females (> 15001RMB)
      was higher. Individual business owners and farmers consumed lesser antioxidant
      vitamins than the other counterparts. The highest vitamin E intake was found in
      the currently unemployed men and retired women. BMI was positively associated
      with the intake of antioxidant vitamins excepted for the obesity group. The
      result suggests that the consumption of antioxidant vitamins varies with
      characteristics of socio-demographic status. Health promotion programs, such as
      suggestions on eating more fruits and vegetables should be targeted at the
      elderly, the less educated, lower income families and rural community.

PMID- 11321944
TI  - [Change of inhabitant dietary pattern in Shandong province during 1988-1997].
AB  - Food consumption data of some bigger cities and towns of Shandong province during
      1988-1997 had been collected and analyzed. The results showed that the
      consumption of cereals and vegetable in 1997 tended to be decreased and the
      consumption of meat, egg, fruit and milk in 1997 tended to be increased. The
      desirable dietary pattern (DDP) scores for cities and towns were 82.5, 78.7 in
      1988, and 93.3, 88.4 in 1997 respectively. All these changes indicated that the
      dietary quality improved markedly but the consumption of bean and milk are not
      enough.

PMID- 11321945
TI  - [Evaluation on the effect of synthetic hydroxyapatite for drinking water
      defluoridation in field study].
AB  - In order to evaluate the effect of synthetic hydroxyapatite on drinking water
      defluoridation, a coagulative precipitation method and a flow column system was
      tested in the fields. The defluoridation capacity of coagulative precipitation
      method was 4.19 mg/g, and the method was simple on operation, but more reagents
      were needed with high cost for operation. The defluoridation capacity of flow
      column system was 6 mg/g and the saturated hydroxyapatite could be reused after
      regeneration. The operation of household defluoridator based on flow column
      system is simple, with low cost and high capacity in defloridation. The system
      will be applied in the fluorosis areas.

PMID- 11321946
TI  - [Methanol method for the preparation of template DNA from blood for polymerase
      chain reaction].
AB  - A methanol method for the preparation of template DNA for polymerase chain
      reaction (PCR) from peripheral blood specimens was established. A diameter of 3
      mm blood spots on paper were punched and fixed in methanol for overnight.
      Deionized water was then added. After boiling and centrifuging, the supernatants
      reserved DNA. The blood blot of specimen is easy to be obtained and reserved in
      low cost. The experiment technique is high in efficiency.

PMID- 11321947
TI  - [Evaluation on the performance of formaldehyde analyzer with standard
      formaldehyde gas generated by diffusion tube].
AB  - The performance of portable formaldehyde analyzer was tested by a standard
      formaldehyde gas generation system, the gas was generated by diffusion tube. The
      evaluation included testing the zero, calibrating the drift, response times and
      the accuracy of the analyzer, and testing the effect of relative humidity. In
      compare with the standard method (AHMT method GB/T16129) testing in the fields,
      the overall relative uncertainty of the formaldehyde analyzer was 7%.

PMID- 11321948
TI  - [Measurement of lead in high-salt food with sulfuric-nitric acid to treat food
      ash].
AB  - Lead in high-salt food was measured by treating the ash with sulfuric-nitric
      acid, and diluting lead standard with sodium sulfate to eliminate the disturbance
      of chloride in detecting lead with atomic absorption spectrophotometry. The
      minimum detection limit was 0.10 mg/kg. The relative standard deviation is 1.72%,
      5.00% and 7.14% while the amount of lead was 8.70, 2.40 and 1.40 micrograms
      respectively. The recovery varied between 90.0%-109.0%. There was no significant
      difference (P > 0.05) of the lead content between the mentioned method and
      extraction flame photometry. The amount of lead is higher obviously than that of
      other two methods by eliminating the disturbance of chloride. The method was
      simple, precise and accurate, and suitable for hygienic examination.

PMID- 11321949
TI  - [Poisoning from eating horseshoe crab and its prevention and treatment].
AB  - During the past three years on investigating and studying the poisoning of eating
      Horseshoe crab, it has been discovered that the major cause of the poisoning on
      eating Horseshoe crab in south region along the seacoast of China was taking
      tetrodotoxin from Carcinoscorpius rotundicauda by mistake; the symptoms of some
      others from eating Horseshoe crab were the result of allergic reactions from
      eating Tachypleus tridentatuscause, similar to the reactions from eating shrimp
      or crab, and which could be cured with chlorpheniramine. The effective prevention
      measures are not eating Horseshoe crab, especially the young ones. The size of
      young Carcinoscorpius rotundicauda is similar to the size of the nonpoisonous
      Tachypleus tridentatuscause. It is very easy to be confused and easy to eat by
      mistake. The treatment of the poisoning from eating Horseshoe crab is similar to
      the treatment of tetrodotoxin by removing the toxins from body.

PMID- 11321950
TI  - [Effects of heat shock protein 70 overexpression on apoptosis of K562 cell caused
      by hyperthermia].
AB  - In order to observe the effects of heat shock protein 70(HSP70) on the apoptosis
      of K562 cell caused by hyperthermia, HSP70 was induced by pre-heating K562 cells
      at 40 degrees C and the levels of HSP70 were detected by RT-PCR. Cell apoptosis
      caused by hyperthermia at 43 degrees C was observed by Fluid cytometry (FCM) DNA
      content analyses. The results showed that HSP70 increased with the prolong of pre
      heating time and reached the top level on pre-heating for 120 min and lasted for
      several hours. A lower apoptosis rate and less DNA ladder forming in the pre
      heated cells than those not pre-heated. It is concluded that the higher
      expression of HSP70 induced by pre-heating treatment could inhibited the
      apoptosis caused by hyperthermia.

PMID- 11321951
TI  - [Role of metallothionein in the resistance of rat osteoblasts to zinc excess and
      deficiency].
AB  - This study is expected to investigate the role of metallothionein(MT) in the
      resistance of osteoblasts to high or low zinc conditions. Antisense MT
      oligonucleotide was used to reduce the content of MT in osteoblast. Cellular MT
      content was determined by silver/hemolysate saturation method, and the
      cytotoxicity was measured by the activity of LDH releasing from damaged cells.
      The results showed that antisense MT oligonucleotide markedly decreased the
      resistance of osteoblast to zinc excess and zinc deficiency. It suggested that MT
      played an important role in the modulation and maintenance of intracellular zinc
      homeostasis of osteoblasts.

PMID- 11321952
TI  - [Study on the removal of arsenite from dispersed drinking water].
AB  - The feasible methods for oxidation and removal of arsenite[As(III)] from
      dispersed drinking water were based on the removal of arsenate[As(V)] by ferric
      sulfate. The results showed that the spotaneous oxidation of As(III) to As(V) was
      very slow and could not be enhanced by aerating for 24 h. The removal rate of
      As(III) could reach that of As(V) when pre-aerating water samples with ozone for
      60 s, putting 7.5 ml/L hydrogen peroxide solution, adding 2.5 mg/L javelle water
      (sodium hypochlorite) or 15 mg/L bleaching powder(numerated by chlorine). The
      oxidation by using javelle water was rather stable when samples were varied in pH
      value, hardness, initial concentration of As(III) and As(III)/As(V) ratio. The
      effective oxidation could be reached with 1.25 mg/L javelle water when the
      initial concentration of As(III) was < or = 0.8 mg/L. Moreover, the field study
      also confirmed the oxidation effect of javelle water. It is suggested that
      javelle water is an effective, economic and technologic feasible oxidationagent
      for removing arsenite from dispersed drinking water.

PMID- 11321953
TI  - [Study on the quantitative structure toxicity relations of chlorophenols in some
      aquatic species].
AB  - The quantitative structure-activity relations between electronic structure of
      chlorophenols and their toxicity to Bluegill and Guppy were were studied. The
      electronic structure parameters of fourteen chlorophenols were calculated by
      using CNDO/2 method. The quantitative structure-activity relationships between
      electronic structure parameter of chlorophenols and their toxicity to Bluegill
      and Guppy were were discussed respectively by step regression analysis. Two
      linear equations were obtained as follows: (1) for Bluegill, LC50 = -122.493 +
      20.334 sigma Q pi R; (2) for Guppy DLC50 = -100.263 + 16.639 sigma Q pi R. The
      results showed that the toxicity of chlorophenols to Bluegill and Guppy were
      increased as the sum of pi-charge (sigma Q pi R) at the carbon atom on benzene
      ring increased.

PMID- 11321954
TI  - [Disinfection for cistern water].
AB  - Rainwater is often collected into cisterns (pits or tanks) for household using as
      drinking water source in the rural areas of the northwest and the southeast coast
      in China, where no enough fresh water resource is available. However, the total
      number of bacteria and coliforms in the cisterns water was higher than the
      standard of that in drinking water. In order to ensure the safety for drinking,
      the effectiveness, conditions of treatment and cost for such disinfection methods
      compared with solar radiation, ultraviolet (UV), chloridation, micro-filteration
      and KDF were studied in 10 households in Cixi of Zhejiang Province and Weiyuan of
      Gansu Provinces, respectively. The micro-filteration is more compatible for
      bacteria removal in the tanks, while chloridation more for disinfection in the
      underground pits.

PMID- 11321955
TI  - [Estrogenicity of black cohosh (Cimicifuga racemosa) and its effect on estrogen
      receptor level in human breast cancer MCF-7 cells].
AB  - The estrogenicity of Black Cohosh (Cimicifuga racemosa, CR) was tested in vivo
      and in vitro and its effect on estrogen receptor (ER) level of human breast
      cancer MCF-7 cells were investigated. Based on the body weight of animals, 75,
      150 and 300 mg/kg of CR were administered by tube feeding to immature female mice
      for 14 days. Estrus was observed and the uterine and ovary weights of mice were
      measured. The optimal dose of CR for the growth of MCF-7 cells was screened by 3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assay.
      Subsequently, Growth curves of MCF-7 cells in blank control, 4.75 micrograms/L of
      CR and 0.3 nmol/L of 17 beta-estradiol groups were observed for 5 days. ER level
      in MCF-7 cells was analyzed by indirect immunofluorescence assay in flow
      cytometry. The results showed that uterine weight increased with the increasing
      dosage of CR and the days of estrus was significantly prolonged in the 300 mg/kg
      group (P < 0.05). The concentration of CR at 4.75 micrograms/L showed the
      strongest enhancement effects (64.7%). The doubling time (TD) of cell growth in
      CR group and 17 beta-estradiol group were 32.1 h and 31.7 h respectively, which
      were shorter than that of blank control (TD = 35.3 h). Additionally, 4.75
      micrograms/L of CR significantly increased ER levels compared with the blank
      control (P < 0.01). Taking all the results together, CR has an estrogen-like
      action. The enhancing effect of CR on ER level is one of the potential mechanisms
      involved with its therapeutic role in climacteric syndrome.

PMID- 11321956
TI  - [Comparison of seminal vitamin B12, folate, reactive oxygen species and various
      sperm parameters between fertile and infertile males].
AB  - Vitamin B12(VB12), folate and reactive oxygen species(ROS) in human semen from
      both fertile and infertile males, and their relationships with other parameters
      were observed. Semen samples from 44 infertile and 176 fentile control subjects
      were collected and measured based on the guidelines issued by WHO. The results
      showed that no significant differences on semen VB12 and folate were observed
      between fertile and infertile groups(P > 0.05). However, the levels of ROS in
      infertile group were significantly higher than those in fertile group(P < 0.01).
      The morphological defects and low motility of sperm in infertile group was
      significantly higher than those in fertile group(P < 0.01). A positive relation
      was observed between the levels of ROS production and the morphological defect of
      sperm(P < 0.01). There was a significant negative correlation between the levels
      of VB12, folate and ROS(P < 0.01) in semen. It is interesting to note that the
      values of ROS also show a significantly positive correlation with sperm motility
      (P < 0.01). A significant differences of ROS levels between fertile and infertile
      group with negative white blood cells in sperm was also observed. It is concluded
      that the increase of ROS on the morphological defect of sperm is one of the most
      important factors related to poor sperm quality and human infertility.

PMID- 11321957
TI  - [Effect of cholesterol deficiency on the membrane fluidity of Jurkat T
      lymphocytes].
AB  - The mechanism of cholesterol deficiency on inhibiting the proliferation of T
      lymphocytes was investigated on cell membrane fluidity by using fluorescence
      polarization measurement, 3H-TdR incorporation test and flow cytometer analysis
      in Jurkat cells, in order to clarify the importance of cholesterol in maintaining
      the normal function of lymphocytes. The results showed that cell membrane
      fluidity was increased, cell proliferation was inhibited and blocked on G0/G1
      phase in Jurkat cells after being cultured with lovastatin (an inhibitor of rate
      limiting enzyme for cholesterol synthesis) for 3 days. When the cells were
      treated with LDL. The changes could be partially buffered. These results suggest
      that the change of membrane fluidity may be caused by cholesterol deficiency on
      the proliferation of Jurkat cells.

PMID- 11321958
TI  - [Protective effect of erigeron injections on hepatotoxicity induced by intestinal
      ischemia-reperfusion in mice].
AB  - The liver injury was induced by intestinal ischemia-reperfusion and the
      protective effect of erigeron injection (EI) was studied in mice. The results
      showed that serum alanine transaminase (ALT) and glutathione S-transferase (GST)
      activity increased while the root of superior mesenteric artery was blocked with
      non-injury artery clap for 20 minute and reperfusion for 1 hour. EI could protect
      the above changes induced by intestinal ischemia-reperfusion. EI could reduce the
      activities of serum ALT and GST, decrease the content of hepatic MDA and
      significantly increase the activity of SOD. The pathological changes of
      hepatocytes induced by intestinal ischemia-reperfusion were less in EI groups.
      These results suggested that EI could protect the liver of mice from injury
      induced by intestinal ischemia-reperfusion. One of the mechanisms of
      hepatoprotective action was related to the antioxidative function of erigeron.

PMID- 11321959
TI  - [Effect of zinc on adrenocorticotropic hormone secretion in the pituitary cell
      line AtT-20].
AB  - The effect of zinc on adrenocorticotropic hormone (ACTH) secretion in the
      pituitary cell line AtT-20 was studied. Different concentrations of zinc(10(-8)
      to 1 mmol/L) were added to the medium and ACTH was determined 12 hours later. The
      findings revealed that zinc within certain concentrations could promote the
      secretion of ACTH in AtT-20 cells.

PMID- 11321960
TI  - [Effect on manganese exposure on blood prolactin and plasma renin activity].
AB  - In order to study the adverse effects of manganese on neuro-endocrine and
      cardiovascular system, radioimmunoassay (RIA) was used to test the blood
      prolactin concentration and plasma renin activity among manganese-exposed
      workers. The result showed that the blood prolactin concentration and Plasma
      renin activity in manganese exposed workers were significantly higher than those
      of control group. It suggested that manganese exposure might affect the function
      at tubero-infundibular area and renin-angiotensin aldosterone system.

PMID- 11321961
TI  - [Geographical divisions of rat transmissible diseases].
AB  - In order to prevent rat transmissible diseases, it is necessary to know the
      geographical distribution of rats, their external parasitic arthropod and rat
      borne disease in human, and to make a graph of geographical division. Stratified
      sampling was conducted by county to capture rats, and to sort out flea for
      identification of their genus and species. A total of 55,064 rats sorting as 6
      families, 17 genera and 21 species were captured, and a total of 34,733 flea
      sorting as 4 families, 25 genera and 53 species were picked. Three kinds of rat
      borne diseases, namely plague, leptospirosis and epidemic hemorrhagic fever have
      been occurred and epidemic in Shanxi Province. Following the general principles
      for geographical division, Shanxi Province was divided into 4 sub-regions: (1)
      basin among mountains and prairie in Yanbei; (2) loess plateau, hill and prairie
      with shrub in the west; (3) hill, shrub and basin, prairie with forest in the
      middle part; (4) hill, basin with forest and prairie in the southeast. When
      bubonic plague was epidemic, its transmissible mode was probably Meriones
      meridianus--Xenopsylla conformis--Mus musculus, Rattus norvegicus--Xenopsylla
      cheoopis--human. Bubonic plague has been occurred within Xingxian and Linxian
      conxian counties of the second sub-region. Leptospirosis has been occurred in
      Xiangfen county of the third sub-region, the source of infection was from pigs
      instead of rats. Epidemic hemorrhagic fever has been occurred in the third and
      fourth sub-regions, the source of infection was mainly from Ruttus norvegicus.

PMID- 11321962
TI  - [Seasonal variation of the preponderance of fly species in Jinhua city area].
AB  - The seasonal variation of the preponderant fly species in Jinhua city area was
      observed and analyzed from June to November in 1998 and from March to November in
      1999. The preponderant fly species catching with regular method in Jinhua city
      area were C. megacephala, M. sorbens, L. seriata and L. cuprina, and A. grahami
      was also a preponderant species in several other some months. The peak season for
      C. megacephala was in summer, M. sorbens one peak from summer to autumn, L.
      seriata and L. cuprina in spring and autumn, and A. graham merely appeared in
      early spring and late autumn.

PMID- 11321963
TI  - [Malformations in cortical development in patients with epilepsy. Neuroimaging of
      17 cases].
AB  - This article reviews Malformations of Cortical Development (MCD) diagnosed by
      Magnetic Resonance Imaging (MRI) in a series of patients with epilepsy. This
      study spans a five year period. The frequency of these malformations was 7.1%.
      Most of these were focal or multifocal and the most common ones were
      polymicrogyria (35.3% of the patients), heterotopia (29.4%), and focal cortical
      dysplasia (29.4%). The frontal lobes were the most frequently affected regions.
      The various MCD encountered reflect the wide spectrum of MCD leading to epilepsy.

PMID- 11321964
TI  - [Hypertrophic olivary degeneration. Semiology with magnetic resonance].
AB  - Hypertrophic Olivary Degeneration is a type of transneuronal degeneration caused
      by lesions in the dento-rubro-olivary pathway. It involves the inferior olivary
      nucleus and is a unique type of degeneration because it is associated with
      hypertrophy of this nucleus. The authors report MRI findings in 10 patients with
      Hypertrophic Olivary Degeneration, whose exams were reviewed.

PMID- 11321965
TI  - [Behcet's disease. Assessment with magnetic resonance of involvement of the
      central nervous system].
AB  - Behcet's disease is a chronic multisystemic inflammatory disease that usually
      presents in the young adult. Central nervous lesions occur in 5 to 7% of patients
      and are the most severe manifestations of this disease. METHODS: We
      retrospectively reviewed the MR images of patients with neurological
      manifestations of Behcet's disease evaluated in the Neuroradiology Department of
      Garcia de Orta Hospital and the MRI center of Caselas, Portugal, between 1994 and
      January 2000. RESULTS: There were 8 cases of Neuro- Behcet. Patients' ages ranged
      from 24 to 46 years (mean 36.25). There were 4 males and 4 females (male/female
      ratio = 1:1). In 3 cases (37.5%) there was brainstem involvement, the basal
      ganglia and thalamus were affected in 2 cases (25%) and the internal capsule and
      corona radiata in 2 cases (25%). In 3 cases (37.5%) there was telencephalic white
      matter involvement and in 1 case (12.5%) the spinal cord was involved.
      CONCLUSION: The topography of the lesions, the absence of a defined arterial
      territory distribution and the partial or total regression of lesions over time
      help to distinguish BD from other vasculitic processes and
      inflammatory/demyelinating diseases.

PMID- 11321966
TI  - [Progressive multifocal leukoencephalopathy. Role of imaging in its diagnosis.
      Perspectives].
AB  - We review five cases of Progressive Multifocal Leukoencephalopathy (PML),
      confirmed by biopsy in three cases and by LCR JC virus research by PCR
      (polymerase chain reaction) in two cases. We analysed the lesions and different
      forms of imagiological presentation, concerning location, mass effect, contrast
      enhancement and progress, and emphasize the importance of some atypical patterns.
      Reference is also made to the role of imaging in its diagnosis and new
      techniques, such as Spectroscopy and Transfer Magnetization, to avoid brain
      biopsy.

PMID- 11321967
TI  - [Neuroradiology of Kallmann's syndrome].
AB  - The present study refers to the magnetic resonance characteristics observed in a
      group of three patients with clinical and laboratory evidence of Kallmann's
      Syndrome. This disease, also named olfactogenital dysplasia, affects the normal
      gonadal and olfactory development and is clinically characterized by the
      association of hypogonadotrophic hypogonadism and anosmia/hyposmia. The study
      protocol, which included the attainment of sagittal and coronal T1-weighted
      MPRAGE (Multiplanar Rapid Acquisition Gradient Echo) volumetric sequences, showed
      defective rhinocephalon development in all patients, expressed by the
      aplasia/hypoplasia of the olfactory bulbs/tracts and/or of the olfactory sulci.
      The changes observed corroborate the predictable imaging of this genetic disorder
      and have been mainly visible in the coronal slices obtained. The results shown
      are more clear evidence that magnetic resonance is an effective method to show
      the abnormalities in the olfactory region that are invariably found in this
      syndrome.

PMID- 11321968
TI  - [Spontaneous intracranial hypotension].
AB  - The authors consider some clinical and radiological aspects of spontaneous
      intracranial hypotension syndrome, based on the knowledge obtained from three
      clinical situations. Postural headache was a constant complaint. In all cases,
      magnetic resonance imaging data obtained was diffuse dural enhancement and, in
      two cases, bilateral subdural fluid collections. The increasing recognition of
      this syndrome led to its distinction from meningeal inflammatory or neoplasic
      conditions, sparing the patient from unnecessary investigation.

PMID- 11321969
TI  - [Magnetic resonance imaging of aqueductal flow in patients with normal
      hydrocephalus pressure].
AB  - The treatment of patients with the so-called Normal Pressure Hydrocephalus (NPH)
      consists of ventricular shunting, but only in some cases is there clinical
      improvement. The selection of patients for ventricular shunting is usually based
      on the response to the evacuating lumbar punctures of the cerebrospinal fluid
      (CSF), but new MRI techniques of flow measurement have been used successfully. In
      this study, a group of 58 patients, 28 of which with NPH, is presented. Flow
      quantification of the aqueductal CSF using the MR Phase Contrast technique was
      performed in all of them. The authors conclude that the method is sensitive and
      can be a valid criterium in the selection of patients for ventricular shunting.

PMID- 11321970
TI  - [Medullary and intracranial metastases of myxopapillary ependymoma].
AB  - After a brief introduction about the clinical, histological and therapeutic
      characteristics of myxopapillar spinal ependymoma of cone medullar and filum
      terminale, three cases with medullar and intracranial seeding of myxopapillar
      spinal ependymoma are retrospectively reviewed. Surgical resection was total in
      the child and partial in the adult cases and the histological results were
      myxopapillar. The diagnosis was made by CT and MRI between 1-2 months before
      surgical treatment. No extra-neural tumour was found. The mechanisms and factors
      that influence the seeding of this type of tumour are discussed. The most
      important literature is reviewed and the cases discussed. The authors stress the
      importance of surgery on prognosis and the need of an MRI of the whole neural
      axis, particularly in children, and subtotal exeresis in adults.

PMID- 11321971
TI  - [Atypical meningioma].
AB  - One case of intradiploic meningioma, causing partial occlusion of the superior
      longitudinal sinus, with subsequent visual trouble and another of lipomatous
      meningioma with great fat content and very calcified, that was found in a LCR
      fistula study of the cranial anterior stage, are described by the authors as
      atypical meningiomas.

PMID- 11321972
TI  - [Preoperative applications of cortical mapping with functional magnetic
      resonance].
AB  - The authors describe a clinical experience in cortical brain mapping by
      Functional Magnetic Resonance Imaging (FMRI) with a 1.0 T MR scanner with BOLD
      technique and echo-planar imaging (EPI). A brief review is made of the
      theoretical basis of the BOLD technique and of the different functional tasks
      used. The main clinical applications of FMRI cortical mapping regarding the
      sensorimotor cortex of the hand and of language are mentioned. The experiment
      involves 29 patients, 16 with gliomas (G), 7 with mesial temporal sclerosis (MT
      S) and 6 with arteriovenous malformations (AVM) The most frequent clinical
      applications were the determination of the topographic relationship of the
      cerebral lesions with these eloquent cortices as well as the presurgical
      lateralization of language in medically intractable epileptic patients. The
      results are discussed in order to assess the FMRI cortical mapping role as a
      noninvasive method for presurgical planning, regarding the evaluation of the
      potential neurosurgical risks and the identification of viable cortex regions
      displaced or reorganized as a consequence of disease. Additionally, FMRI cortical
      mapping can also assess the atypical speech representations and the language
      lateralization of the patients.

PMID- 11321973
TI  - [Three-dimensional magnetic resonance reconstruction. Significance of
      neurosurgical planning].
AB  - The authors describe their experience with three-dimensional (3D) MRI
      reconstructions of the cerebral cortex in neurosurgical planning of cortical and
      subcortical lesions. The majority of the lesions were located on the cerebral
      hemispheres; there were also few cases of posterior fossa lesions. The authors
      selected three clinical cases to demonstrate the interest of 3D MRI. The authors
      describe another image processing method based on the three dimensional models
      obtained by using Curvilinear Multiplanar Reformatting (CMR) for the
      identification of subtle focal dysplastic lesions in patients with epilepsy. The
      advantages and disadvantages of those 3D MRI reconstructions methods are
      discussed and a comparison with conventional cross-sectional images is mentioned.
      The main disadvantages are the raw data relative to long acquisition time and the
      difficulty in sometimes establishing the cleavage plane between the cortex and
      extra-axial structures (e.g. young patients; lesions with great mass effect;
      lesions ventrally located in the cerebral lobes). In conclusion, the 3D MRI
      reconstructions of the cerebral cortex reveal additional information to
      conventional cross-sectional images and permit a precise location of the lesions.
      This is essential in some circumstances for neurosurgical planning and strategy,
      improving neurosurgical performance and patient outcome.

PMID- 11321974
TI  - [Neuroradiology in Portugal].

PMID- 11321975
TI  - [Vascularization of the skull base--review of the literature and illustrative
      cases].
AB  - The dural vascularization of the skull base and proximal nervous structures,
      depends on the external carotid artery, internal carotid artery and vertebral
      artery branches. The authors describe these branches, emphasizing possible
      anastomoses between them, and present images from their own experience. Such
      arterio-arterial anastomosis represent incomplete regressions of embryologic
      arterial connections and are always present, but functionally inactive. It is
      usually in the presence of pathologic situations (stroke, tumours, dural
      fistulas) that they become active and, therefore, special care is necessary if
      endovascular procedures with embolic material are to be performed.

PMID- 11321976
TI  - [Subarachnoid hemorrhage and computerized tomography cerebral angiography].
AB  - We present a review of 57 cases of nontraumatic subarachnoid hemorrhagesubmitted
      to CT angiography of the cerebral vessels. The purpose of our study was to
      estimate the value of CT angiography in the detection of intracranial aneurysms.
      These findings were compared with those from selective angiography. The results
      showed that CT angiography is a rapid, low-risk technique with a low level of
      invasiveness and high specificity and sensitivity in the detection of cerebral
      aneurysms, allowing the planning of endovascular intervention and surgical
      approach.

PMID- 11321977
TI  - [Cerebrovascular disease in pregnancy and puerperium].
AB  - Cerebrovascular diseases are the main causes of neurological events occurring
      during pregnancy and puerperium. METHODS: We retrospectively reviewed the
      clinical records and imaging scans of females presenting with stroke during
      pregnancy or puerperium. We selected the cases with abnormal initial CT and/or
      MRI and a radiological follow-up until stabilization of the neurological
      condition. RESULTS: Eleven patients with ages ranging from 21-38 years were
      found. The hospital admission occurred between the second trimester of pregnancy
      and the first two weeks after delivery. In six cases there was a clinical setting
      of preeclampsia/eclampsia (PE/E): five with reversible encephalopathy syndromes
      (hypertensive-like encephalopathy) and one with a hematoma in a HELLP patient.
      Three other cases had a clinical setting of hypertension, not fulfilling the PE/E
      criteria, presented with hemorrhagic infarct in one case and lenticular hematoma
      in the other two. The other two cases were a subarachnoid hemorrhage in a patient
      with a middle cerebral aneurysm and a cortical venous infarct in a patient with
      lateral sinus thrombosis. CONCLUSION: Hypertension is the major underlying factor
      in peri-partum stroke. PE/E syndrome is the major leading cause of stroke in the
      peri-partum and maternal morbidity/mortality. MRI is very useful in evaluating
      this entity and, may have a positive impact on the management protocol.

PMID- 11321978
TI  - [Tentorium cerebellum fistula. Diagnosis and treatment].
AB  - Among the 17 intracranial dural fistulae treated in the Department of
      Neuroradiology of the University Hospital of Coimbra (17 patients, 28
      embolizations) between 19/10/98 and 20/11/2000, 4 cases (23%) were located on the
      tentorium cerebelli. Three patients were men aged 45, 53 and 56 years old. The
      remaining patient was an 85-year-old woman. All 4 patients were treated by
      embolization. One underwent post embolization surgical interruption of the
      draining vein. The authors analyse clinical presentation, complementary tests,
      therapy and outcome.

PMID- 11321979
TI  - [Dementia as a result of dural vascular malformation].
AB  - A case of dementia can result from encephalopathy caused by venous hypertension,
      produced by a dural vascular malformation (DVM). The authors describe one
      tentorial DVM with sinusal venous drainage and retrograde reflux to the cerebral
      veins (type II), that originated a leukoencephalopathy, and a progressive
      demential symptomatology. This demential status partially regressed after
      surgical treatment.

PMID- 11321980
TI  - [Endovascular treatment of dissecting aneurysms of the posterior cerebral
      artery].
AB  - In the literature, there are few reports of posterior cerebral artery aneurysms
      resulting from isolated dissections. In these cases the treatment is still a
      matter of discussion and includes anticoagulation, surgical intervention,
      endovascular techniques and conservative management. We present five cases of
      Posterior Cerebral Artery (PCA) aneurysms, with angiographic criteria of
      dissection (double lumen, proximal narrowing), all being situated at the P2
      segment, three being close to the P1/P2 junction. In one case, a large aneurysm
      ruptured during the attempted catheterization with subsequent death of the
      patient. In three patients occlusion of the parent vessel was performed with
      Guglielmi detachable coils located proximal to the aneurysm, with no new
      neurological deficits. In the other case there was spontaneous thrombosis of the
      aneurysm. Occlusion of the parent vessel by endovascular techniques in dissecting
      PCA aneurysms has a low probability of neurological deficits and seems to be an
      appropriate approach for these aneurysms.

PMID- 11321981
TI  - [Is it possible to have a consensual terminology in disc diseases?].
AB  - The large variety of concepts and classifications for disc disease (anatomical,
      pathological, surgical and radiological) are reflected in the, often ambiguous,
      terminology of degenerative disc disease used on imaging study reports by
      neuroradiologists and radiologists. The attempts to standardize the nomenclature,
      made by some medical societies, lack general acceptance. This work reflects the
      conviction that morphological characterization of disc disease prevails over the
      anatomopathological due to the limitations of imaging study techniques, including
      magnetic resonance imaging.

PMID- 11321982
TI  - [Dural fistulas of the anterior cranial fossa].
AB  - Dural arterio-venous shunts (DAVS) of the anterior cranial fossa are quite rare.
      There are only a few cases reported in the literature. The authors present 5
      cases of dural arterio-venous shunts (DAVS) of the anterior cranial fossa,
      allowing more data for later reviews of this rare and aggressive localisation of
      DAVS. The clinical set, imaging findings (with emphasis in diagnostic
      angiography), treatment and outcome in these 5 patients are described.
      Haemorrhage was the presenting form in 4 patients; the other case presented was
      investigated for headache. There were bilateral symmetric feeders in two
      patients, unilateral feeders in another two and unilateral predominant feeders in
      one; contribution of the external carotid artery, when present, was always
      minimal. Venous drainage included one or combinations of these: superior sagittal
      sinus, sylvian veins and cavernous sinus. Three patients had venous aneurysms in
      anterior cranial fossa; of these, two presented with haemorrhage, but the third
      one of them has been asymptomatic for 7 years. Three patients were treated by
      surgical exclusion of the shunt and became clinical and angiographicaly normal.
      According to the literature, our cases confirm the highly aggressive behaviour of
      these DAVS. Surgical treatment is an efficacious method of therapy and should be
      done as soon as possible. Embolization can be attempted but is technically
      difficult and eventually too expensive.

PMID- 11321983
TI  - [Fetal magnetic resonance].
AB  - The increasing use of magnetic resonance imaging (MRI) in fetal evaluation is due
      to its excellent structural and morphological resolution. We report nine fetal
      MRI examinations and discuss some of the technical issues related to this
      technique. METHODS: We report nine fetal MRI done in the MRI Center in Caselas,
      Portugal, between January 1999 and March 2000. The fetal ages ranged from 24 and
      33 weeks of gestation. RESULTS: The MRI diagnoses were: one normal case, two
      normal variants, two hydrocephalus due to intraventricular hemorrhage, one corpus
      callosum agenesis, one corpus callosum hypoplasia, one case with white matter
      encephaloclastic lesions and one case of torcular and superior sagittal sinus
      dilatation. In one case the MRI confirmed the ultrasonography (US) diagnosis, in
      two cases the MRI depicted the etiology of the pathologies found with US, in
      three cases there was a suspicion of pathology with US but the MRI was normal or
      had normal variants, and in three cases the MRI diagnoses were different from
      those made by US. CONCLUSIONS: MRI has the highest sensitivity for fetal imaging
      and should be used if the US is insufficient to establish the diagnosis.

PMID- 11321984
TI  - [Caudal regression syndrome. Lumbo-sacral agenesis].
AB  - Retrospective analysis of six cases of caudal regression syndrome, classified in
      accordance with vertebral envolvement. The degree of vertebral agenesis,
      morphology and topography of the conus medularis, neurologic implications (motor,
      sensitive and autonomous) and associated malformations, of particular importance
      in some situations of little significant vertebral agenesis are analyzed.
      Associations with eventual predisponent factors are sought.

PMID- 11321985
TI  - [Lesions of the central nervous system in Adams-Oliver's syndrome].
AB  - The authors report two cases of Adams-Oliver syndrome in 2-year-old children
      characterized by aplasia cutis congenita and terminal congenital abnormalities of
      the limbs. The diagnosis was made at birth and the aplasia cutis was associated
      with extensive skull defects, exposing the dural sinuses. The differences between
      the two patients were essentially the extension and the severity of the scalp and
      limb osteo-cutaneous lesions, associated malformations of the central nervous
      system and complications. In one child we found focal hemimegalencephaly of the
      right hemisphere and in the other one the syndrome was complicated by
      encephaloclastic cerebral lesions and encephalic herniation. Both children have
      survived, but the diagnosis of central nervous system malformations and the
      encephaloclastic lesions associated modified the initial prognosis and the future
      outcome conspicuously.

PMID- 11321986
TI  - [Early infantile ceroid lipofuscinosis -- role of nuclear magnetic resonance in
      the diagnosis].
AB  - The authors report a case of Infantile Neuronal Ceroid Lipofuscinosis and
      emphasize the role of MRI in the diagnosis and follow-up of the disease
      describing a severe progressive cerebral atrophy. Clinical findings and
      laboratory data were reviewed and the importance of palmitoyl-protein thiosterase
      activity is described.

PMID- 11321987
TI  - [Intracranial hemangioma].
AB  - A case of intracranial hemangioma in a neonate is described by the authors. The
      rarity of the condition raised differential diagnosis problems.

PMID- 11321988
TI  - [Inflammatory response, cholesterol metabolism, and arteriosclerosis].
AB  - The goal of the present review consists on the relationship between inflammatory
      disorders, such as that represented by systemic granulomatous diseases like
      sarcoidosis, and the cholesterol metabolism and its implication in the
      atherosclerosis process. Serum amyloid A is an acute phase reactant that
      transiently binds to the high density lipoproteins during an inflammatory
      response. Serum amyloid A may act either displacing apo A-I, which in turn result
      in increased catabolism of high density lipoproteins, or inhibiting lecithin
      cholesterol acyltransferase activity which leads to low levels of esterified
      serum cholesterol. This lipoprotein alteration together with a direct effect of
      the serum amyloid A on the endothelium of the atheromatous plaque suggest a
      potential pathophysiological link between the inflammatory responses expressed by
      the serum concentrations of amyloid A and the development of the atherosclerotic
      process.

PMID- 11321989
TI  - [Panhypopituitarism secondary to brain injury].

PMID- 11321990
TI  - [Primary hypothyroidism and rheumatic polymyalgia of simultaneous onset].

PMID- 11321991
TI  - [Arachnoid cyst in a patient with AIDS and neurologic clinical aspects].

PMID- 11321992
TI  - [Social insufficiency: concept and method for its clinical evaluation].

PMID- 11321993
TI  - [Social insufficiency: concept and method for its clinical evaluation].

PMID- 11321994
TI  - [Social insufficiency: concept and method for its clinical evaluation].

PMID- 11321995
TI  - [Myocardial infarction caused by amphetamine].

PMID- 11321996
TI  - [Primary hemochromatosis in asymptomatic youngsters].

PMID- 11321997
TI  - [Hemochromatosis: interest vs confusion].

PMID- 11321998
TI  - [Vasospasm following chemotherapy with 5-fluorouracil].

PMID- 11321999
TI  - [Factors associated with amputation in diabetic patients with foot ulcer].
AB  - OBJECTIVE: To analyse risk factors for amputation in diabetic foot ulcers.
      METHOD: We have studied 152 diabetic patients (in 14 food ulcers treatment was
      amputation) who were attendance between January 1996 and June 1998 in the
      diabetic foot Unit. Subjects with gangrene were excluded. RESULTS: Risk factors
      for amputation were: previous history of amputation (odds ratio 3.7; 1.0113.7),
      proliferative retinopathy, osteomielitis, and independently clinical signs of
      peripheral vasculopathy (7.1; 1.88-27.2) and severe infection (14.4; 2.92-71.2).
      CONCLUSION: Diabetic subjects with foot ulcers and previous history of
      amputation, proliferative retinopathy, osteomielitis, clinical signs of
      peripheral vasculopathy and/or severe infection were a high risk group for
      amputation and in this group aggressive therapeutical and preventive approaches
      should be done in order to prevent amputation.

PMID- 11322000
TI  - [Bronchiolitis obliterans with idiopathic organizing pneumonia. Usefulness and
      yield of diagnostic techniques and procedures in a series of 20 patients].
AB  - OBJECTIVE: To assess retrospectively the utility and the profitableness of the
      diagnostic procedures and techniques in patients with idiopathic BOOP. MATERIAL
      AND METHODS: We studied epidemiological features, clinical manifestations,
      respiratory function tests, chest radiology, and other diagnostic procedures and
      techniques, as well as the evolution and the mortality rates in patients with
      histological diagnosis of idiopathic BOOP during the period 1992-1999. RESULTS:
      20 patients (55% F, 45% M). Age: 64 +/- 15 years old, 50% smokers. The mean
      period elapsed since the beginning of the symptoms and the time of diagnosis was
      51 +/- 30 days. The clinical presentation is of a subacute influenza-like
      illness, with fever, cough, dyspnea and crackles. The more common abnormalities
      were. WBC (10,949 +/- 2,6429 mm3, ESR 85 +/- 86 UI/L, LDH 309 +/- 86 UI/L.
      Arterial blood gas: PaO2 64 +/- 9, PaCO2 35 +/- 3 mmHg. Pulmonary function tests:
      VCF 81 +/- 25%, FEV1/VCF 78 +/- 17%, TLCO 74 +/- 9%, TLCO sb 77 +/- 4%.
      Radiological evaluation: bilateral multiple patchy alveolar opacities 75%),
      solitary focal lesion (15%) and interstitial opacities (10%). The bronchoscopy
      and BAL 10/20 (50%). Transbronchial biopsy 12/20 wit diagnosis (60%). The video
      assisted thoracoscopic lung biopsy 1/20 (5%) and open lung biopsy 7/20 (35%).
      Recurrences 8/20 (40%). Mortality rate 3/20 (15%). CONCLUSIONS: The idiopathic
      BOOP is a benign entity clinic inespecific, associated to hypoxemia and bilateral
      alveolar opacities. The transbronchial biopsy is a diagnostic procedure
      alternative to the open lung biopsy, in a compatible clinico-radiological
      context. The response to treatment is acceptable although it presents frequent
      exacerbations, and low mortality rate.

PMID- 11322001
TI  - [Inadequate technique in the use of inhalers in patients seen at a pneumology
      clinic].
AB  - OBJECTIVE: To assess inhalation technique in out-patient attending a respiratory
      ward who were using inhaler devices, and to identify factors associated with
      misuse of these therapies. METHOD: One hundred and seven patients were
      prospectively studied, of whom 100 completed the study; Inhalation technique was
      evaluated using a previously elaborated check list. We searched for significant
      differences between individuals with good or bad inhalation technique. RESULTS:
      Mean age: 68 +/- 11 years. 68 males and 32 females. Only 31% of cases were
      observed to make no inhalation errors when first evaluated. Individuals using
      metered-dose inhalers without spacer chamber made significantly more mistakes
      than patients using other devices. The main factor associated with poor
      inhalation technique was found to be the absence of adequate supervised
      instruction when the treatment was first prescribed. General practitioners were
      less likely to offer this instruction than other specialists. We did not find
      significant associations between inhaler misuse and patients' age, sex or the
      setting (hospital or ambulatory ward) where the treatment was first prescribed.
      CONCLUSIONS: Incorrect use of inhalers is a frequent finding, and an adequate
      instruction seems to associate with improvement of patients' skills with use of
      these devices. Health personnel should be aware that inhalation technique
      instruction is essential ingredient of patients' management.

PMID- 11322002
TI  - [Quality of life associated with the health of patients with HIV infection
      measured with the Health Questionnaire SF-36].
AB  - OBJECTIVES: The aim of the study was to known the influence of HIV-infection in
      health related quality of life (HRQL). We have used clinico-immune variables and
      progression mortality presented by the disease. PATIENTS AND METHODS: From March
      1997 through March 1998 a total of 300 HIV-infected patients were carried out the
      Health Survey SF-36. We included a control group (also 300 patients) who suffered
      chronic viral hepatitis and potentials risks for the HIV-infection. We calculated
      the Cronbach s alpha coefficient to measure the reliability. We used clinical and
      biological data (count of CD4 lymphocytes in periphery blood) to related the
      IIRQL to the severity of the disease. To decide the progression mortality of the
      disease it was carried out a continuation along six mouths. RESULTS: The HIV
      infected patients had lower punctuations in all dimensions of SF-36 that control
      group and population values of reference. The values of Cronbach s alpha
      coefficient are situated up of 0.7 (range 0.75-0.91) in all measurements. The
      critical phaseAIDS patients (with AIDS diagnosis and/or CD4 lymphocytes < 200
      mm3) showed lower punctuations in all measurements except for mental health.
      Thirty-seven patients (14.2%) displayed new events to AIDS diagnosis and twenty
      one died (8.1%). The severe immunodepresion (OR: 4.3; CI 95%: 1.6-11.8), previous
      AIDS diagnosis (OR: 3.4; CI 95%: 1.48.1), the physical function dimension in the
      SF-36 (OR: 0.3; CI 95%: 0.1-1.1) and the body pain (OR: 0.2; CI 95%: 0.1-0.8)
      were predictor factors to the progression-mortality of the disease. CONCLUSIONS:
      The SF-36 as a measure of the HRQL in HIV-infected population show a high
      internal consistency, that is able to discriminate patients with severe
      immunodepression and could help to predict more appropriately the progression of
      the disease.

PMID- 11322003
TI  - [Primary actinomycosis of the abdominal wall. Description of 2 cases and review
      of the literature].
AB  - We report two cases of isolated abdominal wall actinomycosis and review 18
      previously reported cases to further characterize the clinical findings and the
      therapeutic management of this syndrome. This diagnosis would be advocated in
      patients with a palpable abdominal mass of subacute appearance with a previous
      history of digestive medical illness, diabetes, abdominal surgery, or prolonged
      IUD use. In contrast with other actinomycosis locations, remarkable data were a
      more elevated mean age of patients; a female predominance; a prevalent location
      of mass in abdominal lower left quadrant; and a shorter duration of
      symptomatology before to diagnosis. The CT is the first choice for imaging study
      and percutaneous needle aspiration would be recommended for definite diagnosis.
      The long-term antibiotic therapy, with or without percutaneous drainage, is the
      first treatment choice because is very effective and made unnecessary a more
      invasive surgical management. The prognosis is excellent with adequated
      treatment.

PMID- 11322004
TI  - [Aneurysm of the left subclavian artery: infrequent cause of upper pulmonary
      mass].
AB  - Subclavian artery aneurysm is an uncommon condition. Usually is arteriosclerotic
      in origin. Its clinical features are scarce and generally are due to compression
      of the neighbourhood structures or ischemic, embolic or, less frequently, rupture
      of it. Diagnosis is performed by an arteriography or a computed tomography scan.
      Treatment includes the surgical reaction or the embolization. We report the case
      of a patient with a left subclavian artery aneurysm and review the most important
      clinical features of this entity.

PMID- 11322005
TI  - [Hashimoto's thyroiditis and Sjogren syndrome. Association or autoimmune multiple
      syndrome?].
AB  - A case of Hashimoto's thyroiditis associated with incomplete Sjogren's syndrome
      is revised. Both immune disorders are together not just as a casual event, but
      literature says that common mechanisms could have something to be. Previous
      publications express that autoimmune thyroid dysfunction is frequently associated
      with primary Sjogren's syndrome and should be sought clinically and by laboratory
      test in all these patients.

PMID- 11322006
TI  - [Thrombopenia associated to localized scleroderma].
AB  - Two patients are reported with localized scleroderma who developed
      thrombocytopenia. One of these patients had a positive antinuclear antibody (ANA)
      and Anti-DNA antibodies tests. The occurrence of thrombocytopenia in localized
      scleroderma suggests an autoimmune mechanism, by the response to steroids and the
      presence of positive autoantibodies. This possible association emphasizes the
      need to look for hematologic disorders in patients with systemic, as well as
      localized scleroderma.

PMID- 11322007
TI  - [Chest wall destruction: unusual presentation form of pulmonary nocardiosis].
AB  - Nocardia spp infection is associated with immunosuppresion states, neoplasms and
      immunosuppresors and glucocorticoids prolonged treatments. Pulmonary involvement
      is the most typic feature and the dissemination to chest wall and subcutaneous
      cellular tissue is uncommon. We report one case of pulmonary nocardiosis by
      Nocardia asteroides, in a diabetic patient without others risk factors,
      manifested as a chest wall abscess with fifth rib destruction. The treatment with
      cotrimoxazol after lesion drainage was successful. We review the literature and
      remain the different diagnostic and therapeutics attitudes.

PMID- 11322008
TI  - [Efficacy of inhaled zanamivir in the treatment and prevention of influenza].
AB  - The aim of this work is to evaluate the efficacy of zanamivir in the treatment
      and prevention of influenza. This drug is a neuraminidase inhibitor that is
      effective against both A and B influenza viruses. Five randomized, double-blind,
      placebo-controlled, clinical trials have been published, showing a reduction in
      the duration of flu symptoms between 1 and 2.5 days. A greater benefit is seen in
      the patients with influenza-confirmed infection, with fever and when the
      treatment begins in the first 30-36 hours. For the prevention of influenza, two
      placebo-controlled clinical trials have been published, where flu incidence was
      reduced by 50-67%. The characteristics of zanamivir (efficacy, safety and lack of
      resistance) make it an appropriate option for subjects not protected by
      vaccination and for those with high risk of complications.

PMID- 11322009
TI  - [Attention Internet! Web sites on myoarthropathies of the mastication system].

PMID- 11322010
TI  - [Amalgam and other restoration materials. Opinion of dentists in 3 different
      language regions of Switzerland on their side effects. A survey of 1520 men and
      women dentists in Switzerland].

PMID- 11322011
TI  - [Prescriptions and consumption of hypnotic and anxiolytic drugs in the South
      University Hospital of Marseille].
AB  - An investigation of prescription and consumption of hypnotic and anxiolytic drugs
      in hospital was carried out and has associated a transverse prescription study
      and a prospective consumption study. The prescription study was undertaken on one
      day in several medical departments of Sainte-Marguerite Hospital in Marseille in
      February 1999. Of the 91 hospitalized patients included, 42 (46 per cent) had
      been prescribed a hypnotic or anxiolytic. Furthermore, the quantities of drugs
      taken out of the pharmacy during the month of February were 1.54 time more than
      those prescribed. This discrepancy was even more obvious in the case of certain
      benzodiazepines such as bromazepam (ratio from 1 to 4) and lorazepam (ratio from
      1 to 8). Self-prescription and patients being supplied without a prescription are
      the hypotheses advanced to explain this phenomenon.

PMID- 11322012
TI  - [The French system of evaluation of dependence: establishment in a legal system].
AB  - The French system of evaluation of dependence has been defined in the French
      Public Health Code by decree 99-249 of 31 March 1999. It was created by health
      authorities 10 years earlier and concerns dependence and abuse, which were
      previously just submitted to control under the designation of non-conforming use
      and misuse. The consultative function of the narcotics and psychotropics
      commission has been reinforced and its mission extended to include evaluation.
      Cooperation with different actors has been organized. This is based on the
      complexity of the methods of evaluation and the impact of decisions concerning
      control and/or information. The same principles organize the cooperation of this
      system at the European and international levels.

PMID- 11322013
TI  - [Analgesic effects of topical opioids: are they effective?].
AB  - Recent research has revealed the presence of opioid receptors in inflamed
      peripheral tissues. This gives rise to the possibility of treating the pain
      caused by wounds with the advantage of reducing the secondary effects related to
      the use of opioids and at the same time rendering their use more efficacious. The
      theory of a peripheral analgesic action of opioids has been tested in a variety
      of situations, in particular in brachial plexus blocks and intra-articular
      injections. In addition, the analgesic effect of opioids has been tested by
      cutaneous application for various conditions but on only a limited number of
      patients. On the basis of these case reports, we cannot conclude that the
      peripheral use of opioids is efficacious and the topical use of opioids cannot be
      recommended unless done within the framework of a controlled clinical trial.

PMID- 11322014
TI  - [Ursodeoxycholic acid and prevention of tacrine-induced hepatotoxicity: a pilot
      study].
AB  - Ursodeoxycholic acid is a protective agent against liver toxicity caused by some
      drugs. In the present pilot study, we assessed the effect of this bile acid on
      tacrine-induced hepatotoxicity. Fourteen patients with a diagnosis of Alzheimer's
      disease received tacrine and ursodeoxycholic acid (13 mg/kg/day) for 105 days.
      Serum ALAT was the main evaluation criterion. Serum levels of ALAT were compared
      with those of 100 patients who had been treated with tacrine in the same centre.
      In patients receiving ursodeoxycholic acid, ALAT serum levels were normal in 93
      per cent of cases vs. 69 per cent in control patients and moderate hepatotoxicity
      (ULN < ALAT < 3 ULN) did not occur while it was present in 25 per cent of
      controls (p = 0.036). In contrast, the percentage of patients with ALAT > 3 ULN
      was similar in the two groups (7 per cent vs. 6 per cent). These present findings
      suggest that UDC could prevent moderate tacrine-induced hepatotoxicity. These
      results should be confirmed in a controlled therapeutical trial.

PMID- 11322015
TI  - [Levofloxacin adverse effects, data from clinical trials and pharmacovigilance].
AB  - With 5388 patients in the marketing application dossiers and post-marketing
      experience of more than 130 million prescriptions of levofloxacin worldwide, the
      tolerability profile of this anti-infective is now well defined. During clinical
      trials, 12 per cent of patients treated with levofloxacin experienced an adverse
      event considered to be related to the study drug compared with 13 per cent of the
      patients with a comparator. Nausea and diarrhoea were the most frequent adverse
      effects. During clinical trials, the frequency of tendinitis, psychotic episodes
      and seizures was less than 0.1 per cent. Following recent concerns with some
      fluoroquinolones, specific attention was paid in post-marketing surveillance
      worldwide. The notification rate of significant severe liver injuries (hepatitis,
      necrosis, hepatic failure) has been less than 1 for 5 million prescriptions.
      Cardiac tolerability is satisfactory and the phototoxic potential of levofloxacin
      is one of the lowest amongst fluoroquinolones.

PMID- 11322016
TI  - [Drug-induced taste disorders: analysis of the French Pharmacovigilance Database
      and literature review].
AB  - Taste disorders, generally poorly studied, have various causes. From 1985 to
      1997, 305 observations of taste disorders imputed to drugs were notified to
      Regional Pharmacovigilance Centres. Patients were on average 54.4 years old and
      58 per cent were women. Quantitative as well as qualitative disorders have been
      observed. Drugs mainly found were: angiotensin converting enzyme inhibitors,
      terbinafine, zopiclone, D-penicillamine, imidazole derivatives, quinolones,
      macrolides, carbimazole and calcium channel blockers. The outcome was favourable
      for 60.3 per cent of patients. The possible efficacy of zinc is discussed. It is
      generally considered that taste disorders are not a serious side-effect, but they
      can reduce the quality of life and lead to poor compliance with treatment.

PMID- 11322017
TI  - [Management, cost and mortality of a cohort of patients with advanced heart
      failure (the EPICAL study)].
AB  - The objectives of this study are to describe the management, outcomes and costs
      of patients with severe chronic heart failure (CHF) and to identify the
      associated socio-demographic and clinical determinants. In 1994, the EPICAL study
      enrolled in a French region a representative cohort of 358 patients presenting
      for the first time with severe CHF (NYHA class III or IV) requiring
      hospitalization. The mean annual cost per patient was 125 652 FF, 92.6 per cent
      of which was associated with in-patient care including the index hospitalization.
      Ten per cent of patients contributed 33 per cent of the total cumulative costs.
      The rate of readmission was very high (20 per cent per month of follow-up) and
      appeared as a major cost driver. Three variables were identified in a
      multivariate logistic regression as the main contributors to cost: the presence
      of co-morbidity, renal insufficiency and marital status (living alone versus with
      spouse). These findings confirmed the major clinical and economic interest of any
      intervention that could lower the rate of readmissions in this group of patients.

PMID- 11322018
TI  - [Liver damage and nonsteroidal anti-inflammatory drugs: case non-case study in
      the French Pharmacovigilance Database].
AB  - This study investigates the relationship between exposure to non-steroidal anti
      inflammatory drugs (NSAIDs) and liver injuries using the French Pharmacovigilance
      Database. We use the case/non-case methodology, where 'cases' were reports of the
      reactions of interest (liver injuries as recorded in the database according to
      the WHO-ART classification including cytolytic and cholestatic hepatitis, acute
      hepatitis, liver enzyme elevations). 'Non-cases' were all reports of reactions
      other than these being studied. Amineptine and acetaminophen were used as
      'positive controls'. Among the 42,913 adverse drug reactions recorded in the
      database between January 1995 and December 1997, 5708 (13 per cent) were liver
      injuries. In comparison with other drugs in the database, liver injuries were
      inversely associated with exposure to NSAIDs, whatever the class of the drugs (OR
      0.3 [0.3-0.4]). In contrast, liver injuries were significantly related to
      acetaminophen (OR 2.1 [1.9-2.3]), and amineptine (OR 14.0 [10.5-18.7]). Naproxen
      and diclofenac were associated with a higher frequency of liver injuries,
      respectively 15.7 per cent and 11.5 per cent. The risk associated with NSAIDs
      alone significantly decreased when the analysis was performed after exclusion of
      hepatotoxic drugs associated with NSAIDs (except for naproxen). The present
      results show the low frequency of liver damage associated with NSAIDs. The main
      factor appears to be concomitant exposure to other hepatotoxic drugs.

PMID- 11322019
TI  - [Parkinson syndrome from diltiazem].

PMID- 11322020
TI  - [Severe skin disease induced by a chloroquine-proguanil combination].

PMID- 11322021
TI  - Loxapine side-effects: 3 case reports of hyperleukocytosis.

PMID- 11322022
TI  - [Skin reaction from colchicine].

PMID- 11322023
TI  - [Bleeding from selective serotonin reuptake inhibitors: a case report].

PMID- 11322024
TI  - [Thioguanine, pancreatotoxicity?].

PMID- 11322025
TI  - Effect of grapefruit intake on carbamazepine bioavailability: a case report.

PMID- 11322026
TI  - Molluscicidal activity of thirty essential oils on Bulinus truncatus.

PMID- 11322027
TI  - [Methods for diagnosing excessive alcohol consumption].

PMID- 11322028
TI  - [Usefulness of carbohydrate-deficient transferrin (CDT) in the assessment of
      abuse and abstinence in chronic alcoholism].
AB  - OBJECTIVE: To evaluate the utility of carbohydrate deficient transferrin (CDT)
      for the chronic alcoholism diagnostic, the recent intake and the abstinence,
      comparing it with the most recognized biological markers, specially the MCV and
      the GGT. METHODS: We study 87 subjects: 22 controls, 42 subjects abstinent
      chronic alcoholics and 23 patient active alcoholics. From the last group we
      subject the middle to a 15 days abstinence period. We compare the CDT with the
      mos recognized markers in the difference groups. RESULTS: We found significant
      difference with MCV and GGT in the chronic alcoholism diagnostic. There were
      significant difference with MCV, GGT and specially CDT in the case of recent
      alcoholic intake. CDT was the only one that shows significant difference in
      recent abstinence. CONCLUSION: According to our results the CDT is a poor marker
      of chronic alcoholism. The classical markers (MCV nd GGT) are better on tha
      propriety. CDT, however, is a valid and effective marker for the recent alcohol
      intake, it is better than GGT and MCV. And it is the only valid marker for the
      recent abstinence. So, we estimate that, it would be advisable the CDT clinical
      use with restringed criterions for the recent alcoholic intake diagnostics and,
      specially for the abstinence one.

PMID- 11322029
TI  - [Diagnostic usefulness of the questionnaire "Alcohol Use Disorders Identification
      Test" (AUDIT) to detect conditions associated with alcohol in hospitalized
      patients].
AB  - OBJECTIVE: To evaluate the diagnostic usefulness of AUDIT (Alcohol Use Disorders
      Identification Test) for detection of alcohol-related problems (ARP) among
      hospitalized patients, to assess the potential differences according to age or
      sex and to compare its diagnostic value with that of some other conventionally
      used measures (CAGE questionnaire and biological markers). MATERIAL AND METHODS:
      This is a cross-sectional study for evaluation of diagnostic tests including 179
      hospitalized patients in a Medicine Unit. Data about weekly alcohol intake were
      collected through a semistructured interview. AUDIT and CAGE questionnaires were
      administered and blood levels of GGT, MCV, AST, ALT, alkaline phosphatase,
      platelet count, trylicerides and uric acid were determined. RESULTS: AUDIT
      sensitivity in detecting ARP was of 98%, specificity was of 94% and area under
      ROC was 0.99 (95% CI: 0.98-1). Its sensitivity was shown to be lower both in the
      female group (94% vs. 99%) and in age group under 60 years (97% vs. 100%). CAGE
      showed a sensitivity of 78% and a specificity of 99%. Among biological markers
      GGT and MCV should be highlighted with sensitivities of 83% and 74% and
      specificities of 53% and 74% respectively. CONCLUSIONS: AUDIT is an effective
      tool for detection of ARP among hospitalized patients. Its diagnostic usefulness
      being lower for females, similar for both age groups considered and clearly
      higher than that of other commonly used measures.

PMID- 11322030
TI  - [J-curve between alcohol consumption and carotid atherosclerosis in patients with
      dyslipidemia].
AB  - BACKGROUND: Cerebrovascular disease is the leading cause of death in Portugal and
      carotid disease is responsible for 20 to 50% of strokes. As dyslipidaemias and
      alcoholism are frequent problems in our country, we planned to examine the
      relationship of alcohol consumption and carotid disease in dyslipidaemic
      patients, a subject that has never been specifically studied, as far as we know.
      METHODS: We studied 102 dyslipidaemic patients, 38 females and 64 males. We used
      the following classification for echo-doppler results; grade 0--normal; grade 1-
      intimal-medial thickening (> or = 1 mm); grade 2--one plaque; grade 3--two or
      more plaques; grade 4--haemodynamic disturbance. We measured several biochemical
      and clinical parameters, including declared alcohol consumption. RESULTS: In a
      stepwise regression we found that age had the highest correlation with carotid
      atherosclerosis, followed by alcohol consumption. Visually we noticed a J-curve
      between alcohol consumption and carotid atherosclerosis, that we confirmed with a
      polynomial regression (r = 0.318, p = 0.0114). Carotid atherosclerosis increased
      only with levels of alcohol consumption over 60 g/day, in spite of even lower
      levels of alcohol consumption being associated with lower HDL-C and higher
      triglycerides compared to abstainers. Apo(a) significantly decreased with levels
      of alcohol consumption over 60 g/day. CONCLUSIONS: In spite of inducing a more
      severe dyslipidaemia, a low to moderate alcohol consumption may not be
      contraindicated in dyslipidaemic patients, with some of the protective effects of
      alcohol probably counterbalancing the worse lipid profile.

PMID- 11322031
TI  - [Acute ethanol intoxication at an emergency room].
AB  - OBJECTIVE: To know the frequency of the acute ethylic intoxications in our
      service, as well as their epidemiologic, clinical characteristics, and associate
      problems. METHOD: A series of variables in patients older than 14 years were
      studied. These patients were assisted at the emergency room by ethylic
      intoxication, and they were separated in two age groups. RESULTS: 472 cases were
      assisted (0.55% of the consultation reasons). 84.1% were men and 40% < 26 years.
      Most of the intoxications in this age group happened during the weekends,
      fundamentally at night, while in the > 25 years, the weekly distribution is more
      homogeneous and there is a bigger number in the afternoons. The relationship with
      traumatic brain injury is smaller in the group of the youths. There were not
      significant differences in the number of traffic accidents. The percentage of
      admissions was 17% in the > 25 years opposite to 5% in people younger than this
      age. Variations with statistical significance were not obtained if we consider
      the number of aggressions, parasuicides, overdoses or association with other
      toxic substances. CONCLUSIONS: The ethylic intoxications show some different
      characteristics depending on the age of the patient (< 26 years old vs. > 25
      years old). In the young people ethylic intoxication is the consequence of a
      "recreational behaviour at weekend's night" fundamentally, and in the adults
      there is a stronger association with traumatisms and admissions and we can't say
      that these one are justified for a bigger incidence of traffic accidents.

PMID- 11322033
TI  - ["Occult" ectopic ACTH secretion syndrome: a case report].
AB  - The occult ectopic ACTH syndrome is ACTH-dependent hypercortisolemia of non
      pituitary origin, and of more than 6 months duration without the diagnosis of the
      origin. We report a 55 years old woman diagnosed of Cushing syndrome and treated
      by mean of bilateral adrenalectomy, in which is discovered an ACTH-secreting
      carcinoid tumor 20 years later.

PMID- 11322032
TI  - [Insular thyroid carcinoma].
AB  - A new case of insular carcinoma of the thyroid gland is presented. It was
      described by Carcangiu et al(1) in 1984 as a poorly differentiated carcinoma,
      less of one hundred cases were published after its description. We report a case
      of a patient who was referred for compressive symptoms caused by a mediastinal
      mass. It was found a tumor of left thyroid lobe strongly adherent to adjacent
      structures, which was informed as a poorly differentiated insular carcinoma. She
      underwent total thyroidectomy and posterior treatment with an ablative dose of
      1311. She is currently free of disease after one year of follow-up. The
      diagnosis, treatment, differential diagnosis with another thyroid carcinomas and
      the rarety of this type of tumors are analyzed. The importance of a correct
      diagnosis is fundamental in order to carry out an aggressive treatment and a more
      exhaustive follow-up in these patients, taken account its behavior and its poor
      prognosis when compared with well-differentiated carcinomas.

PMID- 11322034
TI  - [Micronodular pulmonary infiltration as first manifestation of metastatic
      hepatocellular carcinoma].
AB  - Infectious diseases, as tuberculosis, and metastatic cancers are the main causes
      of multiple pulmonary micronodules on chest radiographs. Many cancers can produce
      this anomaly, but the most common are thyroid, melanoma and gastrointestinal
      (colon and pancreas). Hepatocellular carcinoma can produce lung metastasis, but
      seldom makes bilateral pulmonary micronodules. Here we present the case of a
      woman with a hepatocarcinoma that appeared as a bilateral micronodular disease on
      the chest radiograph.

PMID- 11322035
TI  - [Pulmonary lymphangioleiomyomatosis. Description and course of 2 cases].
AB  - Pulmonary lymphangioleiomyomatosis (LAM) is a rare, serious, chronic disease
      whose etiology is unknown and which affects young women almost exclusively. It
      produces typical clinical and radiological characteristics. Diagnosis is
      confirmed on finding histological evidence of irregular proliferation of the
      smooth muscle cells of the lungs. Treatment is not usually effective and there is
      rapid worsening of the pulmonary function leading to serious respiratory failure
      which often results in the patients death. We present two cases of LAM in women,
      one of whom was 33 and the other 38. In the first case the patient had all the
      pulmonary findings described in the literature, while the second also had
      bilateral renal angiomyolipomas. We discuss the histological, radiological and
      clinical characteristics and evolution of both cases, as well as the treatment
      given. We also review the literature. It is concluded that LAM should be
      suspected in young women who have dyspnea, cough and/or hemoptysis and an
      interstitial radiological pattern, especially when associated with a pleural
      effusion or pneumothorax.

PMID- 11322036
TI  - [Diagnosis and treatment of cancer of unknown origin].
AB  - The carcinoma of unknown primary is a frequent clinical problem and represents a
      very heterogeneous group of neoplasms. Despite data in the literature indicating
      minimal success in determining the location of primary carcinomas, these patients
      continue to be evaluated exhaustively. Clinical treatment is guide by the
      pathological evaluation of the lesion and is very important the special
      pathologic techniques characterizing a potentially curable malignancy or patients
      for whom there is are a specific treatment. The majority of the patients are not
      included in these groups and they should be received treatment in clinical
      trials.

PMID- 11322037
TI  - [Laboratory approximation to the diagnosis and typification of porphyria].
AB  - The relationship between clinical features and specific alterations of heme
      metabolism allows the accurate diagnosis and classification of porphyrias. The
      acute porphyric attack is characterized by frequently confusing clinical pattern
      of abdominal-psiquic- and neurological symptoms. An increased urinary excretion
      of porphobilinogen, which can be quickly detected by the Hoesch test, confirms
      the diagnosis of this acute attack. Increased plasma porphyrin levels are
      associated with skin lesions, which are the characteristic features of the
      cutaneous porphyrias. Their presence is easily and rapidly detected by a
      fluorimetric scanning of PBS (phosphate buffer saline) diluted samples.
      Characterization of the molecular defects in genes coding for the enzymes
      involved in the heme synthetic pathway is complementary to the biochemical
      methods. Molecular analysis permits an accurate classification of those
      biochemically unclassified patients and allows prenatal diagnosis in those
      homozygotic cases where a severe prognosis is suspected.

PMID- 11322038
TI  - [Etiology and risk factors in a sample of 200 consecutive patients with heart
      failure].

PMID- 11322039
TI  - [Primary plasma cell leukemia].

PMID- 11322040
TI  - [Kidney failure caused by sulphadiazine in patients with toxoplasma
      encephalitis].

PMID- 11322041
TI  - [Myoclonus in tuberculous meningitis].

PMID- 11322042
TI  - [New episode of fever of unknown origin 17 years later].

PMID- 11322043
TI  - [Myelitis after varicella zoster virus (VZV) primi-infection: report of a case].

PMID- 11322044
TI  - [Phenytoin neurotoxicity].

PMID- 11322045
TI  - [Anterior ischemic optic neuropathy secondary to Horton arteritis].

PMID- 11322046
TI  - [Bleeding jejunal leiomyoma].

PMID- 11322047
TI  - [Acute mediastinitis with fatal outcome after difficult orotracheal intubation].

PMID- 11322048
TI  - [Welcome to Thieme-connect].

PMID- 11322049
TI  - [Chromosome 5q31 linked corneal dystrophies: outline for a new classification].
AB  - The following article is an attempt to summarise the recent genetic findings in
      chromosome 5q31 corneal dystrophies. It also shows the remarkable correlation
      between genotype and phenotype characterising them. Basically, 6 main
      heterozygote mutations are responsible for 6 different phenotypes, corresponding
      to the following 4 histologic forms of corneal deposits: a) amyloid or lattice,
      b) granular, c) amyloid or lattice and granular, d) non-amyloid and non-granular
      (fibrous).

PMID- 11322051
TI  - [Wavelet representation of corneal topography data after nonmechanical
      penetrating keratoplasty--a clinical study].
AB  - BACKGROUND: Corneal surface irregularities may limit the visual outcome after
      penetrating keratoplasty (PK). Corneal topographers mainly render empirically
      derived and system-specific statistical indices for characterization of
      superficial inhomogeneities which may lack clinical evidence and make inter
      system comparisons difficult. The purpose of this study was to detect and
      quantify focal surface irregularities of the cornea after nonmechanical PK by 2
      dimensional wavelet decomposition based on corneal topography data. PATIENTS AND
      METHODS: Our study included 15 patients with keratoconus and 10 patients with
      Fuchs' dystrophy with all-sutures-out after penetrating keratoplasty. For
      trephination we used the excimer laser MEL60 (Aesculap-Meditec, Germany) (7.5/7.6
      mm diameter in dystrophies, 8.0/8.1 mm in keratoconus, double-running 10-0 nylon
      suture). After suture removal a complete ophthalmological examination including
      OrbScan topography analysis (Orbtec, USA) was performed. The refraction data were
      extracted via "data recorder" and decomposed using 2-dimensional wavelet analysis
      methods (Daubechies-4-wavelets on five scales of resolution). Corneal
      irregularities were quantified (scale 1 = fine details to scale 5 = coarse
      details). RESULTS: All detail coefficients (horizontal, vertical and diagonal)
      correlated statistically significant with the "Irregular Astigmatism" provided by
      the OrbScan-system (p < 0.05). In scale 3 and 4 a relative maximum of the wavelet
      detail coefficients occurred, whereas the coefficients at scale 2 and 5 were
      significantly smaller. The horizontal and vertical detail coefficients correlated
      significantly inversely with the best-corrected visual acuity (p < 0.04). All
      detail coefficients were significantly lower in the patient group with
      keratoconus compared to Fuchs' dystrophy. CONCLUSIONS: Wavelet decomposition of
      corneal topography refraction data allows an analytical isolation and
      quantification of focal corneal superficial irregularities. This algorithm is
      independent of the currently used topography system and allows a smoothing of the
      raw data set adapted to scale of resolution and data compression.

PMID- 11322050
TI  - [Gene therapy in ophthalmology. Review of options and trends in corneal
      diseases].
AB  - BACKGROUND: Gene therapy has gained increasing attention and a number of ongoing
      clinical trials have been initiated. This article provides current perspectives
      and limitations on gene therapy in ophthalmology. Since a number of comprehensive
      studies on gene therapy for retinal diseases already exist, we focus attention to
      the treatment of anterior segment disorders of the eye. MATERIAL AND METHODS: We
      undertook a reference search (DIMDI, PubMed) of articles published between (1989
      2000) using the key words cornea, conjunctiva, eye, gene therapy, and
      keratoplasty. The search was restricted to publications in English, French and
      German. In addition, we incorporated some results of our recent experiments on
      cytokine gene transfer to the cornea. RESULTS: Attention to gene therapy in
      ophthalmology is currently focused on retina and choroidea (40 articles) however,
      an increasing number of publications includes the cornea (12 articles). The
      majority of these contributions deals with improvements in the design of gene
      therapy vectors in particular for targeted application. CONCLUSIONS: Gene therapy
      to the cornea may offer interesting new venues. Currently, insufficient gene
      transfer technologies and safety concerns prevent the broad application in
      humans. However, a broad spectrum of applications can be supposed.

PMID- 11322052
TI  - [Prospective randomized comparative study of frequency doubling perimetry vs
      standard automated perimetry in patients with glaucoma].
AB  - AIM: To compare frequency doubling perimetry (FDP) versus standard automated
      perimetry in glaucoma. To evaluate the reproducibility of both methods. PATIENTS
      AND METHODS: All the patients were tested (full threshold test) twice with both
      FDP (N-30) and Humphrey Field Analyzer II model 750 (HFA) (30-2 procedures) in
      random sequence, within one day. The parameters mean deviation (MD), pattern
      standard deviation (PSD) and measured thresholds per quadrant and center areas
      were evaluated for FDP/HFA comparison in 45 glaucoma patients. The same
      parameters were used for testing the reproducibility of FDP (n = 46) and HFA (N =
      39). Additionally, the center and each quadrant area were checked for any
      deviation in the total deviation probability plots. For statistical analysis
      Kappa coefficients and Bland/Altman plots were used. RESULTS: An average MD (FDP
      vs HFA) of -7.3 +/- 5.8 dB vs -8.9 +/- 7.6 dB and PSD of 6.9 +/- 2.4 dB vs 6.5 +/
      3.6 dB were found. Kappa coefficients denote marginal accordance (kappa: 0.11
      0.38) for area deviations. In a total of 225 areas HFA detected 191 deviations
      and FDP 165. HFA measured more negative deviation compared with FDP in the case
      of MD < -15 dB. The reproducibility was 0.98 (MD) and 0.92 (PSD) for FDP and 0.98
      (MD) and 0.95 (PSD) for HFA (95% confidence interval). CONCLUSIONS: There was
      great conformity between FDP and HFA in glaucoma patients. HFA detected more
      deviations in the total deviation probability plots than FDP. There was a high
      reproducibility of both methods. FDP is an appropriate tool for detecting visual
      field loss in glaucoma patients.

PMID- 11322053
TI  - [Does the dissection depth and thickness of the deep scleral flap affect
      intraocular pressure after viscocanalostomy? A clinico-pathologic correlation].
AB  - BACKGROUND: Non-perforating glaucoma surgery preserves the integrity of the
      trabecular meshwork in order to avoid postoperative hypotony. The purpose of our
      study was to investigate whether the morphologic variability of the excised deep
      scleral flap influences the postoperative intraocular pressure (IOP) after
      viscocanalostomy. METHODS: Light-microscopy of the deep scleral flap was
      performed in 17 patients who had undergone viscocanalstomy. Morphologic
      parameters (thickness and dissection level of the deep scleral flap) were
      correlated with the postoperative IOP. RESULTS: The mean thickness of the deep
      scleral flap was 309 +/- 95 microns; the dissection level was too deep in 5 cases
      (trabecular tissue excised) and too high in 6 cases (no signs of Schlemm's
      canal). The max. preop. IOP was 36.2 +/- 8.5 mmHg and came down to 10.6 +/- 5.7
      mmHg at day 1 postop. and 12.4 +/- 4.9 mmHg at day 3/4 postop. At a median follow
      up of 6 months IOP was 21.7 +/- 5.5 mmHg. A significant correlation between
      postop. IOP and the morphology of the deep scleral flap could not be
      demonstrated. CONCLUSIONS: Variations of the thickness and depth of the deep
      scleral flap showed little influence on the initial IOP level following
      viscocanalostomy. Other factors, f.e. the suturing of the external flap or
      invisible microruptures of the trabecular meshwork, could be of importance for
      the early postoperative IOP.

PMID- 11322054
TI  - [Functional results of posterior chamber lens implantation for traumatic
      cataracts in 22 children younger than seven years--a retrospective study].
AB  - BACKGROUND: Surgical correction of aphakia following traumatic cataract in
      children is discussed controversely in literature. This study shows the
      functional results after cataract surgery with posterior chamber intraocular lens
      implantation in children under 7 years of age. PATIENTS AND METHODS: This
      retrospective study analyzes the visual function of 22 children, who were
      operated after traumatic cataract between 1987 and 1997 at the department of
      ophthalmology, university of Erlangen-Nurnberg with PCL-implantation. Mean age at
      injury was 3 years 10 months +/- 1 year 8 months (range 15 to 76 months); the
      interval between injury and cataract surgery: 2.7 +/- 4.7 months (range 0 to 17
      months). The follow-up time

PMID- 11322055
TI  - [Highly active antiviral and immunosuppressive combination therapy with acyclovir
      and mycophenolate mofetil following keratoplasty in patients with herpetic eye
      disease].
AB  - BACKGROUND: Herpes simplex virus (HSV) infection is the most common cause of
      corneal blindness in developed countries.  Penetrating keratoplasty is the only
      therapeutic option for visual rehabilitation in patients with severely scarred
      corneas.  Recurrence of the underlying disease and allograft rejection (AR) are
      the common causes of graft failure.  Systemic immuno-suppression with cyclosporin
      A is contraindicated due to the risk of HSV recurrence.  The potent
      immunosuppressive properties of mycophenolate mofetil (MMF) have already been
      shown clinically.  By reducing the intracellular guanosid-pool MMF inhibits the
      proliferation of lymphocytes.  As these quanosin-nucleosides also act as
      competing substrates to acyclovir at the viral DNA-polymerase, a synergistic
      effect of MMF and acyclovir might be expected.  The aim of this study was to
      evalute the efficacy and safety of a double-drug regimen with MMF and acyclovir
      in the prevention of acute allograft rejection and HSV recurrence following
      corneal transplantation. METHODS: Patients following penetrating keratoplasty due
      to herpetic eye disease have been treated with MMF 1 g twice dialy and acyclovir
      5 x 200 mg/day for one year.  Primary efficacy variables have been the number of
      acute AR and recurrence of herpetic disease per patient and time.  The number of
      adverse events has been documented for safety analysis. RESULTS: Fifteen patients
      have been enrolled.    The average follow up period was 9.1 (+/- 5.2) months.  No
      graft opacifications have been seen. With two AR and no recurrence of herpetic
      disease the efficacy ofthis therapeutic regimen was supperior compared with
      historical control groups. CONCLUSION: In this first study on the efficacy and
      safety of a double drum regimen with acyclovir and MMF for the control of  acute
      corneal AR and HSV-recurrenct following keratoplasty in patients with herpetic
      eye disease, the combination therapy has been shown to be a safe and highly
      efficient protocol for graft protection.

PMID- 11322056
TI  - [Reduction of ocular pulse amplitude by apraclonidine--prospective double-blind,
      randomized clinical trial with 10 subjects].
AB  - BACKGROUND: The alpha-agonist Apraclonidin lowers effective intraocular pressure.
      Ischemia gains increasing importance in the pathogenesis of glaucoma. 
      Therefore, an antiglaucomatous drug should also be investigated in regard of its
      influence on ocular hemodynamics. METHODS: In a double masked, randomized,
      clinical trial 0.5% Apraclonidin eye drops were applied in 10 health subjects
      twice daily for 8 days.  The control group (10 healty volunteers) received a
      placebo medication (0.9% NaCI) according to the same protocol. IOP, heart rate,
      blood pressure and ocular pulse amplitudes (OBF Labs, UK) were measured at
      baseline (1T0), 90 minutes after instillation of one eye drop (1T90), after 7
      days of therapy (8T0) and again 90 minutes after an acute instillation (8T90). 
      For statistical analysis the wilcoxon test for paried samples was used. RESULTS:
      In Apraclonindin treated subjects IOP dropped significantly (P<0.01) from 15.6 mm
      Hg to 11.4/12.4/10.3 mm Hg (1T0/1T90/8T0/8T90. The control group showed a
      significant reduction at 1T90 (p + 0.01)and at 8T90 (p = 0.005) from 3.22 mm Hg
      to 2.48/31/2.35 mm Hg (1T0/1T90/8T0/8T90), in the control group the pulse
      amplitude remained constant. CONCLUSION: After one week of therapy with 0.5%
      Apralonidin, intraocular pressure dropped as expected in health volunteers.  The
      observed reduction in pulse amplitudes in pulse amplitudes however could have a
      negative effect on long-term therapy in patients with chronic open-angle glaucoma
      .

PMID- 11322057
TI  - [Autologous subretinal transplantation of cultivated porcine iris pigment
      epithelial cells (IPE)].
AB  - BACKGROUND: Subretina transplantation of epithelium may be a therapeutic option
      for surgical treatment of age-related macular degeration (AMD). Various
      experimental data have demonstrated that homologous transplantation of retinal
      pigment epithelium (RPE) can prevent photoreceptor deterioration. However, most
      investigators experienced immunogenic graft rejection when using homologous
      pigmented cells for grafting. Autologous cells were soon considered as an
      alternative for subretinal grafting. Particularly iris pigment epithelium (IPE)
      appeared suitable to replace homologous RPE for it embryogenetic similarity and
      its simple availability. Recent studies have shown, that IPE is capable of taking
      over functions of RPE in maintaining retinal metabolism. the purpose of this
      study was to evaluate if autologous IPE cells would survive when being
      transplanted subretinally. In addition, immunogenic reponses to the presence of
      "foreign" iris pigment cells needed to be excluded. MATERIALS AND METHODS: Iris
      tissue was obtained by peripheral iridectomy in the anesthetized pig. Sheets of
      pigment iris epithelium were separated from the specimens and transferred into
      tissue culture. After the cells had been grown to confluency, cell suspensions
      were injected into the subretinal space of the donor animal's fellow eye. After 4
      weeks, the grafted eye was enucleated and examined histologically.. RESULTS: The
      histological exam revealed that the graft cells had survived in the subretinal
      space. No evidence of immunogenic rejection was observed. CONCLUSION: Autologous
      IPE-cells can survive in the host's sub-retinal space without creating
      inflammatory reactions. Transplanted IPE appears to interact with photoreceptor
      outer segments.

PMID- 11322058
TI  - [Idiopathic sclerochoroidal calcification--case report].
AB  - BACKGROUND: Idiopathic sclerochoroidal calcification is a rare benign disorder of
      the choroid and sclera which has initially been described twelve years ago. 
      Clinically, it is often mistaken for osteoma, choroidal metastasis or
      infiltration in lymphoma leading to exentsive further investigations. CASE
      REPORT: A 68-year-old patient had been referred to our outpatient clinic because
      of unusual fundus changes on both eyes.  Ophthalmoscopic examination revealed a
      yellowish placoid-like lesion in the superotemporal quandrant of the fundus of
      both eyes, the left lesion being more discrete.  Flurescein  angiography and
      echography led to the diagnosis of bilateral ISC. CONCLUSION: Although idiopathic
      sclerochoroidal calcification can easily be diagnosed by echographic and
      angiopraphic examination, it is frequently misdiagnosed for malignant tumors thus
      initiating excessive further investigation.

PMID- 11322059
TI  - [Is it festering in the wrong place? Diabetic retinopathy between politics and
      specialty interests].

PMID- 11322060
TI  - The immuno-inflammatory reaction in Crohn's disease and ulcerative colitis:
      characterisation, genetics and clinical application. Focus on TNF alpha.
AB  - Inflammatory bowel diseases are multifactorial polygenic diseases. The author has
      worked on the characterisation of the mucosal immuno-inflammatory reaction, on
      genetic predisposition and on potential clinical application of blood immuno
      inflammatory markers in these diseases. This paper summarizes some aspects of
      this work, focusing on TNF. Following points are developed: production of TNF by
      inflamed mucosa, genetic control of TNF production, TNF gene polymorphim in
      inflammatory bowel disease, and evaluation of serum TNF as a marker of disease
      activity or evolutivity.

PMID- 11322061
TI  - Long-term terlipressin administration improves renal function in cirrhotic
      patients with type 1 hepatorenal syndrome: a pilot study.
AB  - BACKGROUND: Hepatorenal syndrome (HRS) is a severe complication of liver
      cirrhosis. Recently, ornipressin, a potent splanchnic vasoconstrictor, was
      reported to improve renal function in patients with HRS. However, this treatment
      is associated with a high incidence of vascular complications. Terlipressin is
      thought to be as effective as ornipressin with less systemic complications. AIMS:
      To evaluate the effectiveness and safety of terlipressin administration in
      cirrhotic patients with type 1 HRS. PATIENTS: Twelve consecutive patients
      fulfilling HRS criteria of the International Ascites Club were included in the
      study. Median plasma creatinine and sodium, urine volume and sodium before
      treatment were 3.4 mg% (2.5-4.0); 127 mEq/l (124-130), 500 ml/24 h (100-1031) and
      7 mEq/24 h (1-17). METHODS: Terlipressin was administered i.v. 2 mg bid in 8
      patients and tid in 4 others for at least one week and up to 2 months. RESULTS:
      After one week of treatment median plasma creatinine decreased to 1.8 mg% (1.3
      2.1) together with an increase in urine volume, sodium excretion, creatinine and
      free-water clearance. Three patients underwent successful liver transplantation
      with a near normal renal function after 34, 36 and 111 days. The 9 other patients
      died during follow-up (4 from sepsis, 2 from digestive bleeding and 3 from liver
      failure). No ischaemic complications were encountered during the treatment.
      CONCLUSIONS: Long-term terlipressin administration is safe and effective to
      control type 1 HRS. However, it does not cure the underlying disease and
      therefore, may only be considered as a bridge to a definitive treatment as liver
      transplantation.

PMID- 11322062
TI  - Clinical picture of chronic hepatitis C in children--Polish experience.
AB  - The aim of this study was to investigate long-term clinical, virologic and
      histologic outcome of hepatitis C virus infection in children. Sixty children (16
      girls and 44 boys) have been followed for 1 to 5 years (mean 1.7 +/- 0.9 years).
      HCV RNA and anti-HCV were checked every six months. Biopsy specimens were
      evaluated for the grade of inflammation and stage of fibrosis (scores 0-4). ALT
      was measured every 3 months. Presumed duration of HCV infection was from 1 to 16
      years (mean 7.4 +/- 3 years). Fifteen (25%) children could have been infected by
      blood transfusion, 5 (8%) during surgical procedures, 29 (50%) were multiply
      hospitalized. Twenty-five children infected as neonates had lower staging score
      than 24 infected later in life (p = 0.021). Two girls (aged 13 and 14) were
      diagnosed with acute hepatitis C, with maximum ALT of 1272 U/l and 1638 U/l
      respectively. In 11 children (18%) median ALT of more than 3 times the normal
      value (> 105 U/l) was noted. Six children (10%) had continuously normal ALT.
      Histopathology revealed mild to moderate inflammatory activity (0-2 points) in 52
      children (87%). Seven specimens (11%) were scored for 3 to 4 staging points, 3 of
      them (5%) were diagnosed with liver cirrhosis. We have found statistically
      significant correlation between median ALT and grading (r = 0.36; p = 0.005) as
      well as staging scores (r = 0.32; p = 0.016), median AST and grading (r = 0.36; p
      = 0.006) as well as staging (r = 0.36; p = 0.007) scores but also median GGT and
      staging score (r = 0.39; p = 0.004).

PMID- 11322063
TI  - Vinyl chloride monomer and hepatocarcinoma.

PMID- 11322064
TI  - Annular duodenal stricture due to Brunner's gland hyperplasia.
AB  - A patient with obstructive Brunner's gland hyperplasia presenting as an annular
      duodenal stricture is reported. Surgical biopsy was required to obtain a tissue
      specific diagnosis and obstruction was relieved by performing a Roux-en-Y
      duodenojejunostomy. Brunner's gland hyperplasia poses a diagnostic challenge.
      Conservative management is usually adequate after a histological diagnosis has
      been firmly established.

PMID- 11322065
TI  - Living related adult-to-adult liver transplantation: which patient should benefit
      from this technique?

PMID- 11322066
TI  - Adult-to-adult living related liver transplantation: initial experience.
AB  - The number of adult patients on the liver transplantation waiting lists is
      growing steadily. Adult living related liver transplantation (LRLT) represents
      the ultimate means to expand the donor pool. The success of this model of "small
      for size" grafting relies on strict donor and recipient selection. The choice of
      the graft (2 left and 4 right hepatectomies) was made on the minimal ratio
      between estimated graft and recipient body weights (0.8-1%), necessary to meet
      the recipient's metabolic demands. Our experience with six adults is reported.
      Donor morbidity was minimal (one wound infection); there was no mortality. Four
      (66%) recipients are doing well, two died of infectious complications. All
      recipients had a complicated post-transplant course. Due to its complexity, both
      in donor and recipient, LRLT should only be developed very carefully in
      experienced liver transplant centers.

PMID- 11322067
TI  - [Current developments in thoracic radiology].

PMID- 11322068
TI  - [Current development sin the area of digital thoracic radiography].
AB  - All three currently commercially available systems for digital radiography of the
      chest such as the selenium drum, storage phosphor plates and the flat panel
      direct detector systems provide an excellent image quality that is at least
      equivalent or superior to that of conventional film. Reasons for that are the
      continuously improved detective or dose efficiency of the detector systems and an
      improved image processing. The new direct detector systems have the largest
      potential for dose reduction while storage phosphor and selenium radiographs are
      usually obtained with a dose comparable to that of a 400 speed system. Improved
      image processing algorithms allow for the production of digital images that are
      adapted to the conventional image characteristics within the lung regions
      combined with an increased transparency of the high absorption areas such as the
      retrocardial and retrodiaphragmatic regions.

PMID- 11322069
TI  - [Multislice CT of the lung. Technique and clinical applications].
AB  - With the advent of multislice technology computed tomography experienced a boost
      in image quality, comparable to the introduction of spiral CT one decade ago. In
      the chest, the improved performance may be utilised to scan faster or to obtain
      an almost isotropic spatial resolution. For examinations of the lungs multislice
      CT offers considerable advantages over single slice spiral CT: reduced breathing
      and pulsation artefacts, the ability to cover large volumes with thin slices, the
      simultaneous evaluation of high resolution and standard imaging protocols from
      one data acquisition, high resolution multiplanar sections through the lung
      parenchyma, and 3D techniques like volume rendering and virtual bronchoscopy. In
      this review the technical principles of multislice CT of the lungs are discussed.
      Major clinical applications such as evaluation of focal and diffuse lung disease
      are reviewed.

PMID- 11322070
TI  - [Diagnosis of lung embolism with multislice spiral CT].
AB  - In recent years CT has been established as the method of choice for the diagnosis
      of central pulmonary embolism to the level of the segmental arteries. The key
      advantage of CT over competing modalities is the reliable detection of relevant
      alternative or additional disease causing the patient's symptoms. Although the
      clinical relevance of isolated peripheral emboli remains unclear, the alleged
      poor sensitivity of CT for the detection of such small clots has to date
      prevented the acceptance of CT as the gold standard for diagnosing pulmonary
      embolism. With the advent of multislice CT we can now cover the entire chest of a
      patient with 1-mm slices within one breath-hold. In comparison with thicker
      sections the detection rate of subsegmental emboli can be significantly increased
      with 1-mm sections. In addition the interobserver correlation which can be
      achieved with 1-mm sections by far exceeds the reproducibility of competing
      modalities. Meanwhile use of multislice CT for a combined diagnosis of pulmonary
      embolism and deep venous thrombosis with the same modality appears to be
      clinically accepted. In the vast majority of patients who receive a combined
      thoracic and venous multislice CT examination the scan either confirms the
      suspected diagnosis or reveals relevant alternative or additional disease. The
      therapeutic regimen is usually chosen based on the functional effect of embolic
      vascular occlusion. With the advent of fast CT scanning techniques, also
      functional parameters of lung perfusion can be non-invasively assessed by CT
      imaging. These advantages let multislice CT appear as an attractive modality for
      a non-invasive, fast, accurate and comprehensive diagnosis of pulmonary embolism,
      its causes, effects and differential diagnoses.

PMID- 11322071
TI  - [Bronchial carcinoma screening with low dosage CT. Current status].
AB  - Lung cancer is the most common cause of death from malignancy. It is
      characterized by a favourable prognosis when treated in early stages and a poor
      prognosis in advanced stages. Populations at risk are relatively well defined,
      i.e. heavy smokers and workers exposed to asbestos and radon. Therefore, early
      detection using diagnostic techniques promises reduction of mortality from this
      tumor. Previous studies using chest radiography and sputum cytology were,
      however, disappointing due to poor sensitivity of these tests for early tumor
      stages. The new technique of low-dose computed tomography provides both high
      sensitivity for small tumors and a comfortable examination. As small benign
      pulmonary nodules are common reliable non-invasive diagnostic algorithms are
      required for classification of nodules. Preliminary studies using low-dose CT
      screening in smokers have provided promising results. Prior to a wide application
      of the technique in clinical routine more data are required as to inclusion
      criteria, examination intervals and the effect of screening on mortality
      reduction.

PMID- 11322072
TI  - [Virtual bronchoscopy].
AB  - Flexible bronchoscopy represents a clinically well-established invasive
      diagnostic tool. Virtual bronchoscopies, calculated from thin-slice CT sections,
      allow astonishing immitations of reality although principal differences exist
      between both technologies: the fact that colour representation is artificial and
      concommitant interventions are impossible limits the clinical use of virtual
      bronchoscopy. However, its value increases when calculations can be attained
      within minutes due to technological advancements, and when virtually any chest CT
      is suitable for further postprocessing. Indications, findings and the clinical
      role of virtual bronchoscopy are discussed.

PMID- 11322073
TI  - [Optimizing dosage in thoracic computerized tomography].
AB  - Radiation exposure in computed tomography (CT) by far exceeds radiation dose in
      chest radiography. Dose requirements in CT of the chest, however, are much
      smaller than for the abdomen because of low x-ray absorption in the lungs. This
      article describes scanner parameters that influence patient exposure and image
      quality. Suitable compromises will be explained that allow for dose reduction in
      chest CT without jeopardising image quality. Dose reduction in chest CT should be
      performed depending on the clinical indication and requires active reduction of
      mAs settings. For helical CT, a pitch of 1.5 to 2 should be employed. Dedicated
      low-dose techniques for screening of bronchogenic carcinoma are described. Dose
      reduction decreases image quality but the detrimental effects can be reduced by
      applying proper parameters for scanning and image reconstruction. Thus, images of
      the mediastinum should be reconstructed with a smoothing filter, while a higher
      resolution filter should be used for the lungs. In multislice CT, reconstruction
      of thicker axial or multiplanar sections retains spatial resolution but keeps
      image noise and thus dose requirements low. The effective, weighted CT dose index
      (CTDIw,eff) can serve as a rough estimate of the effective patient dose (E) in
      helical or multislice CT of the whole chest: for most scanners and age groups the
      conversion factors are 0.5 mSv/mGy for females and 0.4 mSv/mGy for males.

PMID- 11322074
TI  - [New developments in MRI of the thorax].
AB  - MRI was not used often for lung imaging due to technical and physical
      limitations. Recent developments have considerably improved anatomical MR
      imaging, and at the same time new perspectives for functional imaging emerged.
      They consist of functional investigations of pulmonary perfusion (contrast
      agents, MR angiography) and ventilation (inhaled contrast aerosols, oxygen,
      hyperpolarized noble gases [He-3, Xe-129] and fluorinated gases [SF6]). New
      parameters can be measured: homogeneity of ventilation, lung volumes, airspace
      size, intrapulmonary oxygen partial pressure, dynamic ventilation distribution
      and ventilation/perfusion ratios. MRI-inherent advantages are: lack of radiation,
      high spatial and temporal resolution, and a broad range of functional
      information. MRI of lung ventilation seems to be more sensitive in the detection
      of ventilation defects than scintigraphy, CT or pulmonary function tests. By
      combining the new strategies the radiologist will be capable to improve
      specificity of the investigations and to characterize lung function impairments.
      The joint assessment of ventilation and perfusion will play a major role in this
      development.

PMID- 11322075
TI  - [High resolution MR-venography of cerebral arteriovenous malformations].
AB  - PURPOSE: The purpose of this study was to evaluate the diagnostic potential of a
      high resolution MR venography technique in patients with cerebral arteriovenous
      malformations (AVM). A high-resolution 3D gradient echo sequence was used with a
      long echo time TE to obtain venous information down to sub-pixel sized vessel
      diameters of several hundred microns. The method is based on the paramagnetic
      property of deoxyhemoglobin and the resulting developing phase difference between
      veins and brain parenchyma at long echo times which leads to signal cancellation.
      The reconstructed venograms were compared with TOF-MR angiography using
      qualitative and quantitative criteria with the conventional DSA serving as the
      reference gold standard. METHODS: In 17 patients with angiographically proven
      cerebral AVM the method indicates its potential in clinical applications.
      Venography was able to detect all AVM whereas TOF-MRA failed in three patients.
      In the delineation of venous drainage patterns MR venography was superior to TOF
      MRA, however, as expected the method detected only about half of the main feeding
      arteries. Due to susceptibility artifacts at air/tissue boundaries or
      interference with paramagnetic hemosiderin, MR venography was limited with
      respect to the delineation of the exact nidus sizes and shapes in ten patients
      with AVM located close to the skull base or in patients having suffered from
      previous bleeding. RESULTS: Although the visualization of draining veins
      represents an important prerequisite in the surgical and radiosurgical treatment
      planning of cerebral AVM, there exist limitations of the technique in regions
      where strong induced static field inhomogeneities are present. CONCLUSIONS: Due
      to its high sensitivity the method may be of special importance in the early
      detection and assessment of small AVM which are difficult to diagnose with other
      MR methods.

PMID- 11322076
TI  - [Administration of MR contrast agents outside of approved indications (off-label
      use].
AB  - PURPOSE: The use of MRI contrast agents outside their labeled indications is
      routine in radiology. However, physicians feel frequently at unease. It is the
      aim of this paper to introduce the medical, juridicial and billing relevant
      issues in order to improve the knowledge on this topic. METHODS: The basis for
      off-label use is the physician's prerogative, which finds its basis in the
      "declaration of Helsinki". RESULTS: Off-label use is allowed under special
      conditions and might be even the medical state of the art. CONCLUSION: The
      necessity for off-label use will continue to increase for MR-contrast agents, as
      clinical trials for registration purpose are quite costly and manufactures
      continuously will concentrate on the essential indications.

PMID- 11322077
TI  - [Space-occupying lesion in the left epigastric area. Gastric stromal tumor].

PMID- 11322078
TI  - [MRI in spinal ligament injuries].

PMID- 11322079
TI  - The effects of negative racial stereotypes and afrocentricity on black couple
      relationships.
AB  - This questionnaire study investigated the relationship between internalized
      negative stereotypes, Afrocentricity, and dyadic trust and adjustment for 73
      Black couples. Internalized negative stereotypes alone generally did not predict
      relationship problems, however, the combination of internalized negative
      stereotypes and high Afrocentricity for the men was associated with decreased
      perceptions of partner dependability, an aspect of relationship trust, and
      decreased dyadic adjustment for both partners. Contrary to predictions,
      Afrocentricity was associated with less perceived partner dependability and
      satisfaction for the couples. Controlling for socioeconomic status failed to
      alter these associations. Findings imply that racial perspectives are important
      predictors of Black couple outcomes and that complex and conflicting racial
      attitudes held by Afrocentric Black men may cause deterioration in Black couple
      relationships.

PMID- 11322080
TI  - The relationship of attributions to marital distress: a comparison of mainland
      Chinese and U.S. couples.
AB  - Research on attribution theory has focused on a number of different social
      contexts. Close personal relationships and marriage in particular have been
      investigated widely. Cross-cultural differences in attribution patterns have also
      been explored, although mostly in relation to academic achievement or employment.
      This article focused on cross-cultural variations in marital attributions. Thirty
      six couples from the People's Republic of China (P.R.C.) and 32 couples from the
      United States (U.S.) were included. Marital attributions were correlated with
      marital distress for both groups. However, the P.R.C. spouses tended to report
      more relationship-enhancing causal attributions than did U.S. spouses. There were
      also some differences in attributions of responsibility and blame across
      cultures. These findings are discussed in relationship to current marital
      attribution theory.

PMID- 11322081
TI  - Physical aggression and marital dysfunction: a longitudinal analysis.
AB  - Shortly after marriage, 56 couples provided data on physical aggression and other
      predictors of marital adjustment. At 6-month intervals over the next 4 years,
      spouses reported on their marital quality and stability. Results indicated that
      marital dysfunction was more common among aggressive than among nonaggressive
      couples (70% vs. 38%) and among severely aggressive than among moderately
      aggressive couples (93% vs. 46%). Aggression remained a reliable predictor of
      marital outcomes after the authors controlled for stressful events and negative
      communication. These findings help to refine developmental models of marital
      dysfunction, which often overlook the role of aggression, and can provide
      information for prevention programs for marital distress, which typically do not
      distinguish between aggressive and nonaggressive couples.

PMID- 11322082
TI  - Differential parenting as a within-family variable.
AB  - Nonshared environmental influences have been found to be important for adolescent
      development. This study of 516 families investigated whether differential
      parental negativity or warmth is linked to adolescent adjustment apart from the
      effect of the level of parenting toward each child separately. After accounting
      for level of parental treatment to the adolescent, the authors found that
      differential parenting to the siblings contributed unique variance in adjustment.
      Significant interactions were found between level of parenting and differential
      parenting. In each case, differential parenting was more strongly linked to
      adjustment when the level of parenting was low in warmth or high in negativity.
      These results are indirect evidence that differential parenting can be considered
      a within-family influence on sibling adjustment and as direct evidence that
      nonshared environmental factors may systematically vary in strength between
      families.

PMID- 11322083
TI  - Coparenting: a link between marital conflict and parenting in two-parent
      families.
AB  - Coparenting is examined as an explanatory link between marital conflict and
      parent-child relations in 2-parent families. Data were collected from 3 samples
      (pilot sample, n = 220 mothers; preadolescent sample, n = 75 couples; preschool
      sample, n = 172 couples) by using the Coparenting Questionnaire (G. Margolin,
      1992b) to assess parents' perceptions of one another on 3 dimensions-
      cooperation, triangulation, and conflict. Main effects for child's age and for
      parents' gender were found for cooperation, and an interaction between parent and
      child gender was found for triangulation. Regression analyses were consistent
      with a model of coparenting mediating the relationship between marital conflict
      and parenting. Discussion addresses the theoretical and clinical importance of
      viewing coparenting as conceptually separate from other family processes.

PMID- 11322084
TI  - Sequential interactions in the parent-child communications of depressed fathers
      and depressed mothers.
AB  - Parental depression predicts adjustment problems and depression in offspring, yet
      little is known about the factors that explain this intergenerational
      transmission. In the present study, the authors examined one model suggesting
      that families with a depressed member may respond differently to positive and
      negative communications than families without a depressed member, differences
      that have been theorized to adversely impact offspring development. The authors
      compared the sequential patterns of parent-child interaction among families with
      depressed mothers, depressed fathers, and nondepressed parents. Positivity
      suppression, defined as decreased rates of positivity following a positive
      communication from other family members, characterized the interactions of
      families with a depressed father, but not those with a depressed mother or no
      depressed parent. Father-child positivity suppression and low base rates of
      positivity were associated with child behavior problems, but not after accounting
      for paternal depression.

PMID- 11322085
TI  - Correspondence among informants on parenting: preschool children, mothers, and
      observers.
AB  - The authors examined the correspondence among preschool children's, mothers', and
      observers' descriptions of parenting in the mother-child relationship along 3
      dimensions (structure, warmth-responsiveness, and hostility). Ninety-four
      children (mean age = 5 years, 3 months) and their mothers, who represent diverse
      ethnic and socioeconomic groups, participated in the project. Preschool children
      were interviewed about their mothers' parenting by means of a developmentally
      sensitive, age-appropriate research tool for assessing the subjective experience
      of preschool children. Mothers responded to a self-report measure on their own
      parenting, and observers rated mothers' parenting behavior during a series of
      interaction tasks designed to elicit the relevant dimensions of parenting.
      Results indicated significantly greater correspondence between observer and child
      report of parenting than that between mother and child and mother and observer
      reports. Explanations for the inconsistencies among informants and implications
      of this finding are discussed.

PMID- 11322086
TI  - Parent-child attachment and monitoring in middle childhood.
AB  - Research on parent-child attachment and parental child rearing practices has been
      pursued independently. The purpose of the present study was to test whether a
      secure attachment relationship is related to parental monitoring and child
      efforts to contribute to the monitoring process. This question was examined in a
      cross-sectional study of third- and sixth-grade children and their parents.
      Attachment-based measures were used to tap child and parent perceptions of
      attachment. Monitoring (i.e., parents' awareness of children's whereabouts and
      activities) was assessed through phone interviews with children and parents.
      Child contributions to monitoring were assessed with parent and child
      questionnaires. A more secure attachment was related to closer monitoring and
      greater cooperation by the child in monitoring situations, especially at sixth
      grade. The findings illustrate the importance of embedding attachment within a
      larger child rearing context.

PMID- 11322087
TI  - Linking parenting processes and self-regulation to psychological functioning and
      alcohol use during early adolescence.
AB  - A longitudinal transactional model was tested linking parenting and youth self
      regulation to youths' psychological functioning and alcohol-use behavior.
      Participants included one hundred twenty 12-year-olds, their mothers, and their
      fathers from whom three waves of data were collected at 1-year intervals.
      Teachers provided assessments of self-regulation, and parenting was assessed from
      multiple perspectives, including youth reports, parent reports, and observer
      ratings. Youths reported their psychological functioning and alcohol-use
      behavior. The data supported the model. Parenting and youth self-regulation were
      stable across time, and self-regulation was linked with changes in harsh
      conflicted parenting from Wave 1 to Wave 2. Parenting at Wave 2 was associated
      with youth self-regulation. Youth self-regulation at Wave 2 mediated the paths
      from parenting practices at Wave 2 to youth psychological functioning and alcohol
      use at Wave 3.

PMID- 11322088
TI  - Positive illusions about marriage among married and single individuals.
AB  - The common tendency to describe one's marriage in unrealistic terms has been
      conceptualized as a positive illusion about marriage. Studies of positive
      illusions have relied on the logical argument that these perceptions are
      unreasonably positive. This reasoning is insufficient, because previous studies
      have relied on volunteer samples with high marital satisfaction and long marital
      duration, both of which could explain rosy evaluations of one's marriage. The
      current series of studies examined whether positive marital illusions are an
      artifact of marital satisfaction and duration. Married and single individuals'
      estimates of their divorce likelihood and other measures of positive marital
      illusions revealed that illusions about marriage are not dependent on a volunteer
      bias, marital satisfaction, or duration. The presence of illusions about a future
      marriage among single individuals suggests that positive marital illusions are a
      cultural phenomenon.

PMID- 11322089
TI  - The conclusions of the Arizona perchlorate study require reexamination.

PMID- 11322090
TI  - Methods and conclusions of the Arizona Perchlorate Study.

PMID- 11322091
TI  - Adverse effects of low-level air pollution on the respiratory health of
      schoolchildren in Hong Kong.
AB  - To evaluate the respiratory effects of long-term exposure to air pollution,
      schoolchildren (ages 8 to 12 years) from two districts in Hong Kong with
      contrasting air quality were studied. Parents of 1660 children completed
      questionnaires on respiratory symptoms, and 1294 children had their ventilatory
      function tested with a spirometer. After adjustment for relevant covariates,
      children living in the more polluted district had increased odds ratios for
      frequent cough (1.74), frequent sputum (1.87), chronic sputum (1.84), and doctor
      diagnosed asthma (1.98). Children of both sexes in the more polluted district had
      significantly poorer lung function, and the differences among girls were more
      marked. The study provides additional evidence for the adverse effects of long
      term exposure to relatively low-level air pollution.

PMID- 11322092
TI  - Occupational risk factors for brain cancer: a population-based case-control study
      in Iowa.
AB  - A number of occupations and industries have been inconsistently associated with
      the risk of brain cancer. To further explore possible relationships, we conducted
      a population-based case-control study of brain glioma in the state of Iowa,
      involving 375 histologically confirmed incident cases and 2434 population-based
      controls. Among men, the industries and/or occupations that had a significantly
      increased risk for employment of more than 10 years included roofing, siding, and
      sheet metalworking; newspaper work; rubber and plastics products, particularly
      tires and inner tubes; miscellaneous manufacturing industries; wholesale trade of
      durable goods, grain, and field beans; cleaning and building service occupations;
      miscellaneous mechanics and repairers; and janitors and cleaners. Subjects who
      worked in plumbing, heating, and air conditioning; electrical services; gasoline
      service stations; and military occupations also experienced a significantly
      increased risk. Among women, significant excess risk was observed for occupations
      in agricultural services and farming, apparel and textile products, electrical
      and electronic equipment manufacturing, various retail sales, record-keeping, and
      restaurant service. Workers in industries with a potential for gasoline or motor
      exhaust exposures experienced a non-significant excess risk of brain glioma.

PMID- 11322093
TI  - The military environment: risk factors for women's non-fatal assaults.
AB  - Little is known regarding environmental exposures for non-fatal violence toward
      women in the workplace. We sought to identify factors associated with non-fatal
      physical assault occurring to women during military service. A cross-sectional
      telephone survey of a national sample of 558 women veterans who served in Vietnam
      and subsequent eras of military service was conducted; 537 women were
      interviewed. Twenty-three percent experienced non-fatal physical assault during
      military service. Rates of assault were consistent across eras of service.
      Military environmental exposures, including sexual harassment allowed by officers
      (P < 0.0001) and unwanted sexual advances while on duty (P < .0001) and in
      sleeping quarters (P < 0.0001), were independent risk factors for assault.
      Environmental factors in the military workplace, including leadership behavior,
      appeared to promote violence toward military women. Such occupational factors can
      be identified and should be eliminated.

PMID- 11322094
TI  - Medical insurance claims and surveillance for occupational disease: analysis of
      respiratory, cardiac, and cancer outcomes in auto industry tool grinding
      operations.
AB  - To evaluate medical insurance claims for chronic disease investigation, claims
      from eight automotive machining plants (1984 to 1993) were linked with work
      histories (1967 to 1993), and associations with respiratory, cardiac, and cancer
      conditions were investigated, in a case-control design analyzed with logistic
      regression. The primary focus was tool grinding, but other important processes
      examined were metal-working, welding, forging, heat treat, engine testing, and
      diverse-skilled trades work. Considerable variability in claim-derived incidence
      rates across plants was not explained by age or known exposure differences.
      Asthma incidence increased in tool grinding (at mean cumulative duration: odds
      ratio [OR], 3.0; 95% confidence interval [CI], 0.90 to 10.0), as did non-ischemic
      heart disease (cardiomyopathy, cor pulmonale, rheumatic heart disease, or
      hypertension; OR, 3.1; 95% CI, 1.26 to 7.6). These trends appeared in models with
      deficits (OR < 1.0) for those ever exposed to tool grinding because of exposure
      response miss-specification, demographic confounding, or removal of high-risk
      workers from the exposed group. The apparent cancer rates identified from claims
      greatly exceeded the expected rates from a cancer registry, suggesting that
      diagnostic, "rule-out," and surveillance functions were contributing. This study
      supports the epidemiologic use of medical insurance records in surveillance and,
      possibly, etiologic investigation and identifies issues requiring special
      attention or resolution.

PMID- 11322095
TI  - The impact of behavioral health risks on worker absenteeism.
AB  - The relationship between behavioral health risks and worker absenteeism was
      investigated. Data on absenteeism and on 10 behavioral health risk areas were
      collected from 35,451 employees. Analyses examined whether higher health risks
      are associated with higher absenteeism, and whether a reduction in health risks
      translates into a reduction in absenteeism. Results revealed that a significant
      relationship existed between health risks and absenteeism in 8 of the 10 risk
      areas examined. Individuals who are at risk are more likely to be absent than
      individuals at low risk. Additional analyses revealed that individuals who reduce
      their risks in the areas of mental health, stress, and back are absent less often
      than individuals who remain at risk. These findings suggest that absenteeism, and
      the costs associated with it, may be controlled by health promotion programs and
      the reduction of health risks.

PMID- 11322096
TI  - Physically demanding work and inadequate sleep, pain medication use, and
      absenteeism in registered nurses.
AB  - Pain and fatigue are early indicators of musculoskeletal strain. This study
      examined associations among eight physical demands and inadequate sleep, pain
      medication use, and absenteeism in 3727 working registered nurses (RNs). Among
      the demands, awkward head/arm postures were associated with each outcome
      (inadequate sleep: odds ratio [OR], 1.96; 95% confidence interval [CI], 1.41 to
      2.72; pain medication: OR, 1.65; CI, 1.12 to 2.24; absenteeism: OR, 1.60; CI,
      1.26 to 2.04). A dose-response relationship was present; as the number of demands
      increased, the likelihood of each outcome increased. Odds ratios for eight
      demands versus no demands were as follows: inadequate sleep (OR, 5.88; CI, 2.30
      to 15.50), pain medication (OR, 3.30; CI, 1.34 to 8.11), and absenteeism (OR,
      2.13; CI, 1.15 to 3.94). Adjustment using multiple logistic regression for
      lifestyle, demographics, and work schedule did little to alter the findings.
      Interventions to promote nurses' health should limit the physical demands of the
      work.

PMID- 11322098
TI  - Trends in bloodborne pathogen exposure and follow-up at an urban teaching
      hospital: 1987 to 1997.
AB  - Health care workers (HCWs) risk occupational exposure to bloodborne pathogens.
      Effective postexposure treatment and testing depend on compliance with follow-up,
      but compliance rates are poorly understood. We examined trends in exposure and
      follow-up at a large teaching hospital after interventions to improve compliance.
      We reviewed exposures from October 1987 to September 1988 (group 1) and July 1996
      to June 1997 (group 2). Data were analyzed for HCW demographics, source patient
      characteristics, and follow-up outcomes. We found that group 2 source patient
      serologic data were obtained more often. Group 1 source patients were more likely
      to be positive for the human immunodeficiency virus (HIV). Group 2 HCWs were more
      likely to be immune to hepatitis B virus, to agree to HIV testing, and to comply
      with follow-up. Follow-up rates remained suboptimal, even after high-risk
      exposures. Non-licensed HCWs were less likely to accept postexposure testing than
      physicians or nurses in group 2. General and targeted interventions to improve
      compliance and follow-up are still needed.

PMID- 11322097
TI  - Farm-related dermatoses in Iowa male farmers and wives of farmers: a cross
      sectional analysis of the Iowa Farm Family Health and Hazard Surveillance
      Project.
AB  - Agricultural workers are exposed to a variety of hazards that increase their risk
      for dermatitis. Nevertheless, the prevalence, patterns, and risk factors for
      dermatitis have not been well characterized among farmers in the United States.
      We assessed the prevalence and risk factors for dermatitis among 382 male farmers
      and 256 wives of farmers in Iowa using a cross-sectional study design. From 1992
      to 1994, we collected data on potential risk factors and dermatitis. The results
      showed that 9.6% of male farmers and 14.4% of wives of farmers reported
      dermatitis during the previous 12-month period. In multivariable models, a
      history of allergy (odds ratio [OR], 8.2; 95% confidence interval [CI], 2.0 to
      33.3) was strongly associated with dermatitis among male farmers. Among wives of
      farmers, some college education (OR, 3.4; 95% CI, 1.1 to 9.9) and exposure to
      petroleum products (OR, 3.1; 95% CI, 1.3 to 7.0) were associated with dermatitis.
      These results can be used to form preventive efforts in controlling farmwork
      related exposures.

PMID- 11322099
TI  - Agricultural contamination of groundwater as a possible risk factor for growth
      restriction or prematurity.
AB  - Agricultural activity on Prince Edward Island poses a potential hazard to
      groundwater, which is the sole source of drinking water on the island. This study
      investigates the potential impact of groundwater nitrate exposure on prematurity
      and intrauterine growth restriction on Prince Edward Island. A total of 210
      intrauterine growth restriction cases, 336 premature births, and 4098 controls
      were abstracted from a database of all Island births. An ecological measure of
      groundwater nitrate level was used to gauge potential exposure to agriculturally
      contaminated drinking water. The higher nitrate exposure categories were
      positively associated with intrauterine growth restriction and prematurity, and
      significant dose-response trends were seen, even after adjustment for several
      important covariates. Nevertheless, these risks must be interpreted cautiously
      because of the ecological nature of this exposure metric. An investigation using
      nitrate levels for individual study subjects is needed to confirm this
      association.

PMID- 11322100
TI  - An updated mortality study of workers at a petroleum refinery in Beaumont, Texas,
      1945 to 1996.
AB  - The present investigation represents an update of a previous cohort mortality
      study of 7543 workers who were employed at a petroleum refinery in Beaumont,
      Texas, for at least 1 year between 1945 and 1996. The updated study covered an
      observation period of 51 years, from 1946 to 1996, with a total of 208,627 person
      years of observation. A total of 3020 (40.0%) cohort members were known to have
      died. The mortality data were analyzed in terms of cause-specific standardized
      mortality ratios (SMRs) and 95% confidence intervals (95% CIs). The overall
      mortality of the cohort was significantly lower than expected when compared with
      that of the general US population (SMR, 95.7; 95% CI, 92.3 to 99.2). Overall
      cancer mortality was also lower than expected (SMR, 85.8; 95% CI, 79.4 to 92.5).
      For specific cancer sites, significant mortality deficits were observed for the
      following: buccal cavity and pharynx, esophagus, large intestine, rectum, larynx,
      lung, and bladder and other urinary organs. No significant increase was reported
      for any site-specific cancer. A non-significant increase in acute myeloid
      leukemia was observed among male employees (SMR, 147.2; 95% CI, 76.1 to 257.2).
      Detailed analyses indicated that the excess was restricted to workers hired
      before 1950. No increase was detected for other leukemia cell-types, non
      Hodgkin's lymphoma, or multiple myeloma. For non-malignant diseases, the majority
      of SMRs were below 100, and no significant increase was observed for any cause.
      In particular, significant mortality deficits were reported for ischemic heart
      disease (SMR, 91.0; 95% CI, 85.4 to 96.9), non-malignant respiratory disease
      (SMR, 61.5; 95% CI, 52.2 to 72.0), pulmonary fibrosis (SMR, 51.0; 95% CI, 22.0 to
      100.4), cirrhosis of the liver (SMR, 47.2; 95% CI, 30.6 to 69.7), and accidents
      (SMR, 81.7; 95% CI, 66.3 to 99.6). Separate analyses of male workers by job
      classification (process and maintenance) were conducted. Mortality from acute
      myeloid leukemia was elevated among employees in maintenance jobs (8 observed
      deaths vs 4.31 expected; SMR, 185.5; 95% CI, 80.1 to 365.6). However, no upward
      trend by length of service was found. A detailed analysis indicated that the
      acute myeloid leukemia mortality excess was limited to maintenance workers who
      were hired before 1950. No other significant excess was detected for any cause
      among maintenance or process workers. These findings from the present study were
      discussed in conjunction with results from previous investigations of employees
      at the Beaumont refinery and with results from other refinery studies. Potential
      limitations of the study were also discussed.

PMID- 11322101
TI  - Hepatitis C screening and prevalence among urban public safety workers.
AB  - This study examines the prevalence of anti-hepatitis C virus by using an enzyme
      linked immunoassay test (EIA-2) in 2447 volunteers (including 1560 police, 678
      fire, and 209 emergency medical service personnel) and a self-reported
      questionnaire on potential occupational and non-occupational risk factors.
      Subjects consisted of 76% men, 54.8% blacks, and 40.3% whites. Twenty-eight
      individuals (1.1%) tested positive, with prevalence rates of 1.1% and 1.3%,
      respectively, among blacks and whites. Although firefighters and emergency
      medical service workers had a higher prevalence (2.3% and 2.8%) than police
      (0.6%), the overall prevalence was lower than that typical of urban populations.
      In a multivariate analysis, the most important risk factors were behavioral, with
      no significant occupational exposure risk observed. Previously reported racial
      differences were not detected in this study, most likely because the subjects
      were of similar socioeconomic status.

PMID- 11322102
TI  - Radiographic abnormalities in long-tenure Vermont granite workers and the
      permissible exposure limit for crystalline silica.
AB  - This study was undertaken to assess the prevalence of radiographic abnormalities
      consistent with silicosis in a group of 600 retired granite workers who were
      receiving pensions. Files of regional clinics and hospitals were searched for
      chest radiographs taken on these men, and 470 x-ray films suitable for
      interpretation were located. After exclusions (women, and men who had worked in
      the granite industry elsewhere), 408 x-ray films were independently read by three
      experienced readers using the 1980 International Labour Office scheme. Dust
      exposures were estimated for workers hired after 1940, when the dust-control
      standard of 10 million particles per cubic foot (mppcf) (equivalent to 0.1 mg/m3)
      was put in place and monitored by the Vermont Division of Industrial Hygiene.
      Dust levels were initially high but were gradually reduced from 1940 to 1954,
      after which average quartz exposures stabilized to a mean of approximately 0.05
      to 0.06 mg/m3; however, about 10% to 15% of samples after 1954 exceeded 0.1
      mg/m3. Of the 408 x-ray films, 58 were taken on workers hired before dust
      controls were instituted in 1940, and 25.9% showed abnormalities (a profusion
      score of 1/0 or greater). A total of 350 x-ray films were taken on workers hired
      in 1940 or after, and the prevalence in this group was 5.7%. The radiographic
      changes in workers hired after 1940 are likely due to excessive exposures during
      the first 15 years of dust control. We conclude that if the exposure standard of
      0.1 mg/m3 is rigorously observed in the workplace, radiographic abnormalities
      caused by quartz dust in long-term workers will be rare.

PMID- 11322104
TI  - The quality of extracorporeal erythrocytes.

PMID- 11322103
TI  - [Improvement of the biochemical rheological quality of whole blood and red cell
      concentrates obtained by leukocyte depletion before storage].

PMID- 11322105
TI  - [Extracellular potassium in filtered and irradiated erythrocyte concentrates-
      parameters and their significance].

PMID- 11322106
TI  - [Acid-base status of stored and washed erythrocytes].

PMID- 11322107
TI  - [Lactic acid production and distribution in erythrocyte concentrates].

PMID- 11322108
TI  - [Can tissue oxygenation profit from red cell transfusion?].

PMID- 11322110
TI  - [Clinical hemorheological data on erythrocyte concentrates in additive solution
      in vivo].

PMID- 11322111
TI  - [Quality control of hemolysis rate of erythrocyte concentrates: a proficiency
      test for determination of free hemoglobin].

PMID- 11322112
TI  - [Determination of storage parameters for erythrocyte concentrates using a
      multiparameter electrode measuring instrument (AVL Omni)].

PMID- 11322113
TI  - [Physiological erythrocyte protection solution].

PMID- 11322114
TI  - [The effect of pentoxifylline on the deformability of erythrocytes in erythrocyte
      concentrates in additive solution].

PMID- 11322115
TI  - [Quality of erythrocyte concentrates in additive solutions--evaluation with
      hemorrheological methods].

PMID- 11322116
TI  - [Gelatin protects erythrocytes in vivo and in vitro against mechanical stress].

PMID- 11322117
TI  - [Immune status of school children of 1st classes under different schooling
      conditions].
AB  - Changes in the immune status of first-form pupils were studied as an child body's
      adaptation index to schooling conditions. A complex of immunological tests
      included the following parameters: T lymphocytes (E-RFC), B lymphocytes, T
      lymphocyte subpopulation, IgA, IgM, IgG, circulating immune complexes (CIC).
      There was a definite relationship of the schooling conditions to the children's
      immunity. The routine one-shift schooling regimen in primary-form pupils is not
      optimal in terms of their adaptation to school, which appears as decreased
      immunological responsiveness. Full-day schooling of junior schoolchildren allows
      them to adapt to their new activities more easily after they enter school, the
      risk for immunological disorders and the likelihood of their related diseases to
      become lower.

PMID- 11322118
TI  - [Diagnosis of formaldehyde allergy].
AB  - Exposure to small-dose environmental agents is a risk factor of
      immunopathological reactions. The levels of formaldehyde-specific IgE were
      comparatively analyzed in 50 children of whom 25 live in the area exposed to
      formaldehyde. Children with varying respiratory allergic reactions comprised a
      study group. To identify allergen-specific IgE, the authors used a method that
      determined formaldehyde antibodies by using the tested allergen (formaldehyde on
      the paper). There were significant group-specific differences in the levels of
      formaldehyde antibodies (3.8 times higher in the study group than in the
      controls). Combined therapy substantially reduced specific IgE whose levels
      returned to the levels observed in the controls. The findings may recommend the
      use of this test for the diagnosis of immune-depended abnormalities and the
      evaluation of their effective treatment.

PMID- 11322120
TI  - Clinical presentation and outcome of brain abscess over the last 6 years in
      community based neurological service.
AB  - Sixty patients with brain abscess were treated at the Neurosurgical Unit of the
      Department of Surgery, Hospital Universiti Sains Malaysia between January 1990
      and December 1996. A retrospective study was done and data were collected from
      the computerise d registry of the Record Unit of Hospital Universiti Sains
      Malaysia. Good results were achieved in patients who were both treated surgically
      and medically. There were only twelve deaths in this group. The main factor that
      influences morbidity and mortality of brain abscess is the clinical presentation
      on admission. The mortality was high in patients treated solely by medical means.
      Death was common in patients who presented with acute onset of symptoms of less
      than one week duration and those with poor mental status. Brain abscess is common
      in the East Coast population of peninsular Malaysia, probably due in part to
      lower socioeconomic status. Efforts should be directed towards prevention of
      infection and early recognition and management.

PMID- 11322119
TI  - [Methodological approaches to evaluation of the toxicity of insecticides].

PMID- 11322121
TI  - Specific characteristics and management strategies of cerebral artery aneurysms:
      report of eleven cases.
AB  - Owing to the deep location of the posterior cerebral artery (PCA) and its close
      relationship with the brainstem and surrounding vital structures, surgical
      treatment of aneurysms in this region is complex. This study was undertaken in an
      attempt to better delineate the surgical risks of PCA aneurysms. A retrospective
      analysis was undertaken in 11 patients with PCA aneurysm surgically treated
      between 1988 and 1996 at Shinshu University and its affiliated hospitals. Data
      regarding surgical strategy, surgical complications and outcomes were analysed.
      Seven aneurysms were saccular (including one mycotic) and the other four were
      fusiform, dissecting, thrombosed and an infundibular dilatation. The locations of
      the aneurysms were at the P1 segment in two patients, P1-P2 junction in two, P2
      segment in six and P3 segment in one. Six saccular non-mycotic aneurysms were
      treated with neck clipping and the other five aneurysms were treated each with
      proximal occlusion of the parent artery, excision of the aneurysm or wrapping.
      All aneurysms were satisfactorily exposed except one large saccular aneurysm.
      Surgical outcomes were either good recovery or moderate disability in 10
      patients, and severe disability in one patient with a large aneurysm due to
      temporal lobe contusion. In conclusion it is the responsibility of the surgeon
      dealing with rare PCA aneurysms to be aware of these specific characteristics and
      to appreciate which surgical technique is appropriate for each patient.

PMID- 11322122
TI  - Detection of craniospinal dissemination of intracranial germ cell tumours based
      on serum and cerebrospinal fluid levels of tumour markers.
AB  - Nineteen intracranial germ cell tumours treated during the past 11 years were
      evaluated retrospectively. The tumours were classified into three groups
      according to the level of alpha-fetoprotein (AFP) and beta-human chorionic
      gonadotropin (HCG) in serum and cerebrospinal fluid, and the optimal treatment
      for each group was determined. Group A consisted of patients with normal titres
      of AFP and HCG, group B of patients with relatively high titres (< 10 times
      normal), and group C comprised patients with higher titres ( 10 times normal
      levels). In group A, an appropriate field and dose of irradiation was necessary
      to prevent craniospinal dissemination. In group B, none of four patients who
      underwent total or subtotal resection of the tumour had craniospinal disseminatio
      n or tumour recurrence, whereas dissemination occurred in four further patients,
      including two who had received radiochemotherapy only, and two who had undergone
      partial resection of the tumour. While patients in group C had dissemination at
      the time of initial diagnosis, most patients in group B developed dissemination
      more than 10 months after initial treatment, suggesting that the type of
      treatment received as first line therapy is important in patients in this group.
      The prognosis of patients in group C, however, was unaffected by the priority
      given to either surgery, radiation or chemotherapy as first line treatment.
      Craniospinal dissemination can be prevented in patients with germ cell tumours
      who have a relative increase in levels of AFP and HCG by aggressive removal of
      the tumours as first line therapy, regardless of the type of adjuvant therapy
      given.

PMID- 11322123
TI  - Subependymal giant cell astrocytoma: clinical and neuroimaging features of four
      cases.
AB  - The clinical history, neuroimaging features, treatments, and outcome of 4
      patients with histologically verified subependymal giant cell astrocytomas (SEGA)
      were retrospectively reviewed. The average age at the time of surgery was 13.3
      years. Headache related to raised intracranial pressure was the first and only
      sign in 2 patients, with the remaining 2 being admitted because of sequential
      neuroimaging studies over several years revealing the growth of 'subependymal
      nodules' into intraventricular tumours. In each case the tumour was in the region
      of Monro's foramen and was associated with ventricular dilatation. On computed
      tomography (CT), multiple subependymal nodules were found in 3 patients, and
      these well circumscribed isodense SEGAs were markedly enhanced by contrast
      medium. On magnetic resonance imaging (MRI), which was obtained in 3 patients, 2
      SEGAs were isointense with the cerebral cortex and one with the white matter on
      T1-weighted images, and on T2-weighted images, 2 were isointense with the cortex
      and one with the white matter. At surgery the tumours appeared to originate from
      the inferolateral wall of the lateral ventricle in the region of the head of the
      caudate nuclei. Total macroscopic removal was achieved in 3 patients, and
      subtotal removal in one patient. Follow up ranged from 4.6 to 13.2 years, and all
      patients have exhibited similar physical and mental conditions to preoperative.
      So far there has been no evidence of any recurrences. The diagnosis and the
      surgical indications for SEGA are discussed, with periodic monitoring with
      neuroimaging studies being recommended even for asymptomatic patients with
      'subependymal nodules'.

PMID- 11322124
TI  - The effects of dexamethasone therapy on permeability, blood flow and iNOS
      expression in experimental glioma.
AB  - Most studies of dexamethasone (DXN) effects on experimental glioma have used
      doses 10-500 higher (on mg/kg basis) than those used for patients with brain
      tumour. The relevance of findings to patients with glioma are therefore
      uncertain. In order to evaluate the effects of clinical doses of DXN (0.22 mg kg(
      1)day(-1)) on the pathophysiology of an experimental glioma we have treated
      rodents with established C6 gliomas for 3 days. The effects of therapy on local
      cerebral blood flow (LCBF), tumour blood flow (TBF), tumour capillary
      permeability (TCP), and inducible nit ric oxide synthase (iNOS) mRNA expression
      were evaluated. DXN caused a significant reduction in TCP (21 +/- 1.9 to 7.7 +/-
      2.2 ml.gm(-1)min(-1)10(-3)) and iNOS mRNA production within and around tumour,
      but no significant change in either TBF or LCBF. The reduction in TCP was
      identical to that reported after higher doses of DXN and is probably mediated by
      glucocorticoid receptors. Further in vivo stud ies using either behavioural or
      neuropathological paradigms in rodents with established cerebral glioma should be
      treated with similar doses of DXN to optimise clinical relevance.

PMID- 11322125
TI  - In normal pressure hydrocephalus, intracranial pressure monitoring is the only
      useful test.

PMID- 11322126
TI  - In normal pressure hydrocephalus, intracranial pressure monitoring is the only
      useful test--the argument against.

PMID- 11322128
TI  - Bibliography of congenital muscular dystrophies--cobblestone lissencephalies:
      series III (1999).

PMID- 11322127
TI  - In normal pressure hydrocephalus, intracranial pressure monitoring is the only
      useful test.

PMID- 11322129
TI  - Phenytoin treatment in the newborn and infant.

PMID- 11322130
TI  - Bibliography. Current world literature. Glaucoma.

PMID- 11322131
TI  - Polarity of click and tone-evoked vestibulocollic reflexes.

PMID- 11322132
TI  - Interactive stereoscopic full-color direct volume visualization for virtual
      reality applications in medicine.
AB  - Only recently, advanced direct volume visualization techniques have been widely
      used due to the availability of low cost hardware accelerators; such techniques
      have a great potential of use for many applications of the virtual reality in
      medicine. We proposed and implemented a low cost system for interactive and
      stereoscopic 3D visualization of the full color visible human dataset. Potential
      use of the proposed system includes anatomical atlases and surgical simulators. A
      prototype of the proposed system is rendering full color volumes with 256 x 152 x
      470 in real time (15-20 Hz) with stereoscopy.

PMID- 11322133
TI  - A virtual reality simulator for bone marrow harvest for pediatric transplant.
AB  - Bone marrow transplant is a relatively new procedure to treat recently considered
      incurable diseases. One important part of the procedure is the process of
      harvesting the donor bone marrow. We are developing a virtual reality simulator
      for bone marrow harvest that integrates interactive stereo visualization and
      force feedback techniques. The main objective is to offer a low cost virtual
      reality system to boost current adopted training methodologies for bone marrow
      harvesting.

PMID- 11322134
TI  - Implementing a virtual reality paradigm in human anatomy/physiology college
      curricula.
AB  - Modes of instruction in the college course called Human Anatomy/Physiology are
      changing. Due to ethical concerns and the ever-increasing source of new
      physiological data, there is a need for enhancements to assist the instructor and
      student. The computer science of virtual reality (VR) provides a method to
      electronically educate, train, prototype, test and evaluate new enhancements to
      the college curricula. This study detailed the modeling and simulation of a
      skeletal human hand with degrees of freedom of movement, which provided the
      students with a physiological representation of some of the movements of the
      hand. The primary objectives of the study were to assess the use of the VR
      simulation by college students and to assess the potential learning outcomes of
      students in their use of the VR simulation. The simulation was implemented into
      classes of Human Anatomy/Physiology as an adjunct enhancement for the students'
      use. The expectation centered on the constructivist theory that students develop
      an analytic outlook to the various articulations of the human skeleton. Positive
      results were shown based on the answers to the questionnaire, summary and post
      test taken by the students, after their use of the VR simulation. The results
      supported the constructivist theory that critical thinking took place. The
      results showed that the virtual reality simulation enhanced the learning ability
      of the students. The recommendations of the study include future experimentation
      to be done on increasing the number of VR simulations, incorporating the VR
      simulations into undergraduate courses, testing the outcomes, and following the
      progression of students into graduate programs that are using VR simulations.
      Faculty and administration are advised to consider implementing the paradigm of
      VR simulations in undergraduate courses of Human Anatomy/Physiology.

PMID- 11322136
TI  - Aid for keratoconus patient.

PMID- 11322137
TI  - Modification of the aspiration port to aid OVD removal and prevent posterior
      capsule tear.

PMID- 11322138
TI  - Permanent diplopia following cataract surgery.

PMID- 11322139
TI  - Multiple capsular tension rings for the prevention of capsular contraction
      syndrome.

PMID- 11322140
TI  - Posterior dislocation of a 3-piece silicone IOL with fractured loop induced by
      Nd:YAG laser posterior capsulotomy.

PMID- 11322141
TI  - Acute hemorrhagic keratoconjunctivitis after LASIK.

PMID- 11322143
TI  - Reduction of tardive dyskinesia with quetiapine.

PMID- 11322142
TI  - Response of atrial natriuretic factor to acute extracellular fluid volume in
      patients with pheochromocytoma.
AB  - BACKGROUND: Patients with pheochromocytoma have been reported to show high
      plasmatic atrial natriuretic factor (ANF) levels. Its source may not be the
      atrium because blood volume, the most important physiological stimulus for ANF
      release, is usually reduced in these patients. METHODS: To evaluate ANF secretion
      functional integrity, we studied three patients with pheochromocytoma before and
      after surgical removal of the tumor. Extracellular fluid (ECF) volume, plasmatic
      ANF levels, and plasmatic renin activity (PRA) were measured. ANF was measured
      before and after an acute saline load of 1.5L in 90 min. RESULTS: Before surgery,
      ECF volume was normal or reduced, and PRA was normal but decreased after the
      saline load. By contrast, ANF was elevated and did not change after the saline
      load. After surgery ANF decreased, ECF volume rose, and the saline load induced a
      significant increase of plasma ANF and reduction of PRA. ANF was present in
      significant amounts in tumoral tissue homogenates. CONCLUSIONS: These data
      suggest that the tumor was the source of ANF in these patients with
      pheochromocytoma because high levels of ANF, despite reduced or normal ECF
      volume, as well as unresponsiveness to acute saline infusion, were found before
      surgery with subsequent normalization after tumor removal.

PMID- 11322144
TI  - Bedside glucose testing systems.

PMID- 11322145
TI  - Re: Altitude as a risk indicator of dental fluorosis in children residing in
      areas with 0.5 and 2.5 mg fluoride per litre in drinking water (Caries Res
      1999;33:267--74).

PMID- 11322146
TI  - Uncertainty about clinical equipoise. Equipose and uncertainty principle are not
      mutually exclusive.

PMID- 11322147
TI  - Lumbar corsets: their effect on three-dimensional kinematics of the pelvis.
AB  - Lumbar corsets have been recommended for low back pain patients as a way of
      stabilizing the lumbar region, facilitating flexion movements, and reducing pain.
      However, little is known about how these devices affect lumbar motion. To
      determine the degree of changes in the lumbar region, our approach was to
      quantify three-dimensional kinematic data of the pelvis in harness-supported
      treadmill walking. Twelve healthy subjects (age=32+/-11.8 years) walked on a
      motorized treadmill at 4.5 km/h with and without wearing a lumbar corset. Three
      external markers overlying the sacrum were tracked by three ultrasound
      microphones, determining a local coordinate system, to obtain pelvic motions in
      the frontal, sagittal, and transverse planes. Raw kinematic data were low-pass
      filtered and normalized relative to the right heel strike. Mean values for net
      angular displacements of the pelvis were calculated for each plane within the 5th
      and 95th percentile. The Student's t-test demonstrated significant differences
      (P<0.001) between the corset/no-corset conditions in the frontal plane. An
      average 40% decrease in the relative pelvis up- and downward movement occurred in
      the frontal plane (4.1 degrees+/-2.9 degrees vs. 7.1 degrees+/-3.3 degrees). The
      analysis revealed no significant differences of net angular displacements in the
      sagittal (2.9 degrees+/-1.4 vs. 3.4 degrees+/-1.7 degrees) and the transverse
      planes (4.4 degrees+/-2.6 degrees vs. 4.3 degrees+/-2.1 degrees).

PMID- 11322148
TI  - Functional outcome after high tibial osteotomy: a study using individual goal
      achievement as the primary outcome variable.
AB  - Functional outcome after high tibial osteotomy (HTO) was evaluated with respect
      to both improvement and goal achievement. Fifty-seven subjects, 32 men and 25
      women, with a mean age of 55 years were examined with the Functional Assessment
      System (FAS) 6 and 12 months after surgery. The FAS is an evaluation system,
      specifically designed to monitor lower extremity dysfunction. It shows a profile
      with preoperative status, individual goal, and postoperative status.
      Statistically significant improvement was seen in 6/20 variables after 6 months,
      and in 10/20 variables after 12 months. When goal achievement was examined, the
      results were not as impressive. The treatment goal was not reached on the group
      level for almost all variables. On the individual level, only 20?N40% of the
      patients achieved the goal as a result of surgery in most variables. Exceptions
      were pain and leisure time/hobbies, where there was a high degree of goal
      achievement. It is possible that postoperative training was inadequate. The
      authors recommend a new randomized study, where patients who receive specific
      individual training related to the individual goal and functional profile are
      compared with a control group.

PMID- 11322149
TI  - Thermal response of skin to cyclic pressure and pressure with shear: a technical
      note.
AB  - The thermal response of skin to pressure alone and to pressure with shear was
      compared under cyclic loading conditions. Stresses were applied to the anterior
      aspect of the leg of three healthy subjects for time intervals up to 10 min, and
      the difference in temperature between the stressed site and a contralateral
      control site was assessed after load release. The thermal recovery time (TRT),
      the time interval between load release and either a maximum or a stabilization in
      the temperature difference vs. time record was determined. Results demonstrated
      that for a resultant stress of 142.9 kPa, TRTs were longer for combined pressure
      and shear than for pressure alone. For Subjects A, B, and C, TRT increases were
      1.5 min, 5.5 min, and 2.0 min respectively. For a resultant stress magnitude of
      71.4 kPa, increases were 1.5 min, 3.5 min, and -0.5 min respectively. Comparing
      responses for different resultant stress magnitudes for pressure-only
      application, TRTs were 1.5 min, 1.5 min, and 5.5 min longer for the 142.9-kPa
      condition than for the 71.4-kPa condition for Subjects A, B, and C. For combined
      pressure and shear, increases were 1.5 min, 3.5 min, and 8.0 min respectively. A
      next step will be to determine if the TRT differences measured here are
      physiologically relevant and have clinical meaning. The thermal response
      assessment method could then potentially be used to quantitatively evaluate the
      effects of different interface design features in lower-limb prosthetics on
      tissue response.

PMID- 11322150
TI  - Voltage-gated sodium channels and the molecular pathogenesis of pain: a review.
AB  - Pain pathways begin with spinal sensory (dorsal root ganglion, DRG) neurons that
      produce nociceptive signals and convey them centrally. Following injury to the
      nervous system, DRG neurons can become hyperexcitable, generating spontaneous
      action potentials or abnormal high-frequency activity that contributes to chronic
      pain. Because the generation of action potentials in DRG neurons depends on
      voltage-gated sodium channels, an understanding of the expression and function of
      these channels in DRG neurons is important for an understanding of pain.
      Molecular studies have indicated that at least eight distinct voltage-gated
      sodium channels, sharing a common overall motif but encoded by different genes
      that endow them with different amino acid sequences, are present within the
      nervous system. The DRG neurons express six different sodium channels, including
      several sensory-neuron-specific sodium channels that are not present at
      significant levels within other parts of the nervous system. Following injury to
      their axons within peripheral nerve, DRG neurons down-regulate some sodium
      channel genes, and up-regulate others. As a result, a different repertoire of
      sodium channels is inserted into the DRG neuron cell membrane following injury,
      which is a molecular change that is accompanied by changes in physiological
      properties that contribute to hyperexcitability in these cells. Sodium channel
      expression is also altered in experimental models of inflammatory pain. The
      multiplicity of sodium channels, and the dynamic nature of their expression,
      makes them important targets for pharmacologic manipulation in the search for new
      therapies for pain.

PMID- 11322151
TI  - Effect of exercise on perceived quality of life of individuals with Parkinson's
      disease.
AB  - The purpose of this study was to determine if individuals with Parkinson's
      disease (PD) who completed an 8-week, supervised PoleStriding exercise program
      would undergo significant improvements in cognitive skills, activities of daily
      living, motor function, and quality of life. The Unified Parkinson's Disease
      Rating Scale (UPDRS) and the Parkinson's Disease Questionnaire (PDQ-39) were used
      to measure functional independence. Six male volunteers (72.7+/-3.7 years of age)
      performed PoleStriding exercise three times per week for 37+/-3 minutes.
      Differences in the participants' pre- and post-training scores on the UPDRS and
      PDQ-39 were analyzed using the Wilcoxin Signed Ranks Test. A statistically
      significant improvement occurred in the UPDRS (P<0.026) and PDQ-39 (P<0.028)
      scores following the moderate-intensity exercise intervention. The results of
      this nonrandomized clinical trial indicate that an 8-week individualized
      PoleStriding exercise program increases perceived functional independence and
      quality of life in individuals with PD.

PMID- 11322152
TI  - Effect of functional neuromuscular stimulation on postural related orthostatic
      stress in individuals with acute spinal cord injury.
AB  - The purpose of the study was to evaluate the cardiovascular responses of
      functional neuromuscular stimulation (FNS) on postural-related orthostatic stress
      in individuals with acute spinal cord injury. Two tetraplegics and three
      paraplegics participated in this study. A repeated measure design was used in
      which subjects underwent two graded-tilt table (0 degrees, 15 degrees, 30
      degrees, 45 degrees, 60 degrees) orthostatic stress tests with and without FNS
      (randomized treatment order) of the knee extensors and foot plantar flexors.
      Successive one-minute digital readings of heart rate (HR) and blood pressure were
      obtained with an electronic pulse oximeter and automated blood pressure monitor,
      respectively. Analysis of covariance (ANCOVA) revealed significant test position
      (tilt angle) and treatment condition (with or without FNS) main effects, but no
      significant interactions. Between-treatment pairwise contrasts showed that
      systolic blood pressure was lower without FNS for 15 degrees, 30 degrees, 45
      degrees g, and 60 degrees of tilt, while diastolic blood pressure was lower
      without FNS at 30 degrees and 45 degrees of tilt. In contrast, HR showed a
      progressive rise with increasing tilt angle. Functional neuromuscular stimulation
      may be an important treatment adjunct to minimize cardiovascular changes during
      postural orthostatic stress in individuals with acute spinal cord injury.

PMID- 11322153
TI  - Proposed test method for and evaluation of wheelchair seating system (WCSS)
      crashworthiness.
AB  - Safety of motor vehicle seats is of great importance in providing crash
      protection to the occupant. An increasing number of wheelchair users use their
      wheelchairs as motor vehicle seats when traveling. A voluntary standard requires
      that compliant wheelchairs be dynamically sled impact tested. However, testing to
      evaluate the crashworthiness of add-on wheelchair seating systems (WCSS)
      independent of their wheelchair frame is not addressed by this standard. To
      address this need, this study developed a method to evaluate the crash-worthiness
      of WCSS with independent frames. Federal Motor Vehicle Safety Standards (FMVSS)
      207 test protocols, used to test the strength of motor vehicle seats, were
      modified and used to test the strength of three WCSS. Forward and rearward loads
      were applied at the WCSS center of gravity (CGSS), and a moment was applied at
      the uppermost point of the seat back. Each of the three tested WCSS met the
      strength requirements of FMVSS 207. Wheelchair seat-back stiffness was also
      investigated and compared to motor vehicle seat-back stiffness.

PMID- 11322154
TI  - Evaluation of wheelchair back support crashworthiness: combination wheelchair
      back support surfaces and attachment hardware.
AB  - Automotive seats are tested for compliance with federal motor vehicle safety
      standards (FMVSS) to assure safety during impact. Many wheelchair users rely upon
      their wheelchairs to serve as vehicle seats. However, the crashworthiness of
      these wheelchairs during impact is often unknown. This study evaluated the
      crashworthiness of five combinations of wheelchair back support surfaces and
      attachment hardware using a static test procedure simulating crash loading
      conditions. The crashworthiness was tested by applying a simulated rearward load
      to each seat-back system. The magnitude of the applied load was established
      through computer simulation and biodynamic calculations. None of the five tested
      wheelchair back supports withstood the simulated crash loads. All failures were
      associated with attachment hardware.

PMID- 11322155
TI  - Development of frontal impact crashworthy wheelchair seating design criteria
      using computer simulation.
AB  - When designing wheelchairs for use as motor vehicle seats, special design
      criteria must be followed to assure the crash safety of the wheelchair user.
      Failure of seating system components under crash loading conditions could lead to
      serious injury or fatality. In this study, seat and seat-back loading in a
      frontal crash are explored using computer simulation techniques. A previously
      validated simulation model consisting of a powerbase wheelchair and a seated 50th
      percentile male test dummy subjected to a 20g/30mph frontal impact were used for
      the study. Since such a wide range of seating systems are available, parametric
      analyses were conducted to evaluate the influence of surface stiffness and seat
      back angle on wheelchair seat and back loading. Seat loading varied with
      stiffness, ranging from 819-3,273 lb., while seat-back loading was found to be
      between 1,427-2,691 lb., depending upon back stiffness and recline angle.

PMID- 11322156
TI  - Injury risk assessment of wheelchair occupant restraint systems in a frontal
      crash: a case for integrated restraints.
AB  - Obtaining proper occupant restraint fit when using a wheelchair as a motor
      vehicle seat is often difficult to attain with vehicle-mounted restraint systems.
      The comprehensive evaluation conducted in this study illustrates the occupant
      crash protection benefits of wheelchair-integrated restraint systems, as compared
      to vehicle-mounted restraint systems. Using computer crash simulation, occupant
      kinematic and biomechanical measures associated with a 20g/30mph frontal impact
      were evaluated and compared to injury criteria and SAE J2249 WTORS kinematic
      limits. These measures were also used to compile a Motion Criteria (MC) index and
      Combined Injury Criteria (CIC) index for each evaluated restraint scenario. These
      indices provide a composite method for comparing various crash scenarios. With
      the exception of an unsafe 36-inch height off-shoulder shoulder belt anchor
      scenario, the MC index was minimized for the integrated restraint scenario.
      Similarly, the CIC index was also minimized for the wheelchair-integrated
      restraint scenario. This preliminary study emphasizes the need for transfer of
      integrated restraint technology to the wheelchair transportation industry.

PMID- 11322157
TI  - Factors affecting the use of a single switch with assistive technology devices.
AB  - Identifying consumers' motor ability for consistent and reliable control can be a
      difficult yet essential part of a single switch assessment. Current literature
      does not identify the essential components of a single switch evaluation.
      Therefore, the following focus group study was conducted. Six occupational
      therapists with experience in assistive technology service delivery participated
      in a focus group meeting. The purpose of the meeting was to identify essential
      components of a single switch evaluation in the single switch assistive
      technology assessment. Eleven items were identified as essential to the single
      switch assessment. They are: reliability of motor movements, volitional nature of
      movement, safety, movements that are easily performed, endurance, activities and
      positions the client assumes throughout the day and evening, efficiency of
      movement, previous successful movements, ability to perform timed response,
      ability to activate the access device within a given time frame, and time between
      switch closures. The significance of this study is that essential components of a
      single switch evaluation were identified. Using this detailed information should
      lead to optimal switch placement and switch use.

PMID- 11322158
TI  - The effect of filtering and inter-digit interval on the recognition of dichotic
      digits.
AB  - The new compact disc from the Department of Veterans Affairs, Tonal and Speech
      Materials for Auditory, Perceptual Assessment, Disc 2.0 (1998), contains two
      lists of randomly interleaved 1-, 2-, and 3-pair dichotic digits. Two experiments
      are reported, in which the effects of low-pass filtering and inter-digit interval
      on dichotic digit recognition were investigated in adult listeners with normal
      hearing and with mild-to-moderate cochlear hearing loss. Results demonstrated
      that in the filtered condition, as the low-pass cutoff was increased, there was
      an increase in recognition performance for 1-, 2-, and 3-pair dichotic digits.
      When compared to normative data for the materials, findings indicate that the
      interleaved 1-, 2-, and 3-pair dichotic digit materials were essentially
      resistant to the effects of hearing loss. There was no significant change in
      recognition performance as a function of inter-digit interval. The studied 625-ms
      range of inter-digit intervals studied produced consistent recognition
      performance with both groups of listeners.

PMID- 11322159
TI  - A curriculum for training patients with peripheral visual field loss to use
      bioptic amorphic lenses.
AB  - This article describes the experimental protocol used to instruct fifteen
      patients with peripheral visual field loss due to retinitis pigmentosa,
      choroideremia, or Usher's syndrome Type II how to effectively use bioptic
      amorphic lenses. The factors that contributed to the successful use of these
      lenses, as well as difficulties the patients encountered, are discussed. The
      results of the study (published in detail in Szlyk et al. Use of bioptic amorphic
      lenses to expand the visual field in patients with peripheral loss. Optom Vis Sci
      1998;75:518-24) indicate that bioptic amorphic lenses, when combined with a
      comprehensive training program, can expand visual function in the areas of
      peripheral detection, recognition, scanning, tracking, visual memory, and
      mobility.

PMID- 11322160
TI  - Modifying a functional obstacle course to test balance and mobility in the
      community.
AB  - A previously reported functional obstacle course (FOC) developed to assess
      elderly persons with and without balance and mobility impairment was used in a
      hospital-based study of 237 participants. A new modified version of the FOC was
      developed for use in a community-based study, by placing some obstacles next to
      walls instead of between parallel bars. These modifications eliminate the need
      for parallel bars or for extra personnel to interchange the obstacles. We were
      concerned that the modifications could affect performance scores, because
      touching or holding onto the now eliminated parallel bars could influence FOC
      scores under the original scoring system. To determine the effect of these
      modifications on FOC performance, we tested 36 volunteers, (18 fallers [falls
      within last year] and 18 non-fallers), on the modified parts of the old and new
      versions of the FOC. Random testing order and inter-trial rests were used. For
      both the old and new FOC versions, we summed quality and task completion time
      scores from the six modified obstacles (artificial turf, carpet, pine bark, sand,
      up ramp and down ramp) to create scores for quality and time. Our hypothesis was
      that there would be no performance difference between the original and modified
      obstacle course. Using a two-factor repeated-measures analysis of variance, we
      found no difference in quality scores between the two FOC versions and no effect
      of an interaction between faller status and the course versions. We did find that
      the time was approximately 2 seconds longer for the new version; however, the
      time increase was the same for fallers and non-fallers. These data show that
      fallers and non-fallers have comparable performance on both versions of the FOC;
      however, to compare the two obstacle courses we recommend an adjustment of 2
      seconds in time scores. The obstacle course modifications will facilitate more
      extensive and efficient use of the obstacle course as a research tool to assess
      balance and mobility.

PMID- 11322161
TI  - Bed mobility task performance in older adults.
AB  - Difficulty in transferring, the ability to rise in and out of a bed and chair, is
      a common problem in older adults, particularly those residing in skilled nursing
      facilities. Focusing on one aspect of transferring, rising from supine to sitting
      position, we devised a set of bed mobility tasks to test key arm, leg, and trunk
      movements that likely contribute to successful rising from bed. Healthy young
      controls (YC, n=22, mean age 23), and older adults (aged 60 and over) either
      residing independently in congregate housing (CH, n=29, mean age 84) or
      undergoing rehabilitation in a skilled nursing facility (SNF, mean age 77) were
      assessed in the time to rise from supine to sitting and in the ability or
      inability to perform 16 other bed mobility tasks. Trunk function-related tasks,
      specifically those requiring trunk elevation and trunk balance, were most
      difficult for the SNF, followed by CH, and then YC. Tasks focusing on trunk
      flexion strength (sit up arms crossed, bilateral heel raise) and lateral trunk
      strength/balance were the most difficult for both SNF and CH, although there was
      minimal difference in the percent unable to complete each task. The major CH-SNF
      differences occurred in trunk elevation tasks where the upper limb was important
      in facilitating trunk elevation (sit up with head of bed elevation with use of
      arms, sit up with the use of a trapeze, or sit up with use of arms from a flat
      bed position). These findings suggest that to improve frail older adult
      performance on bed mobility tasks, and specifically in rising from supine to
      sitting, training should move beyond improving trunk function (i.e., trunk
      strength). There should be an additional focus, either through therapy or bed
      design modifications, on how upper limb movements and positioning can be used to
      assist in trunk elevation.

PMID- 11322162
TI  - Wheelchair transport safety--the evolving solutions.

PMID- 11322163
TI  - Osteoarthritis and skeletal regeneration.

PMID- 11322164
TI  - [Delegated responsibilities].

PMID- 11322165
TI  - The CCN family of genes: a brief history.

PMID- 11322166
TI  - Report and abstracts on the first international workshop on the CCN family of
      genes.

PMID- 11322167
TI  - NOV (nephroblastoma overexpressed) and the CCN family of genes: structural and
      functional issues.
AB  - The CCN family of genes presently consists of six distinct members encoding
      proteins that participate in fundamental biological processes such as cell
      proliferation, attachment, migration, differentiation, wound healing,
      angiogenesis, and several pathologies including fibrosis and tumorigenesis.
      Whereas CYR61 and CTGF were reported to act as positive regulators of cell
      growth, NOV (nephroblastoma overexpressed) provided the first example of a CCN
      protein with negative regulatory properties and the first example of aberrant
      expression being associated with tumour development. The subsequent discovery of
      the ELM1, rCOP1, and WISP proteins has broadened the variety of functions
      attributed to the CCN proteins and has extended previous observations to other
      biological systems. This review discusses fundamental questions regarding the
      regulation of CCN gene expression in normal and pathological conditions, and the
      structural basis for their specific biological activity. After discussing the
      role of nov and other CCN proteins in the development of a variety of different
      tissues such as kidney, nervous system, muscle, cartilage, and bone, the altered
      expression of the CCN proteins in various pathologies is discussed, with an
      emphasis on the altered expression of nov in many different tumour types such as
      Wilms's tumour, renal cell carcinomas, prostate carcinomas, osteosarcomas,
      chondrosarcomas, adrenocortical carcinomas, and neuroblastomas. The possible use
      of nov as a tool for molecular medicine is also discussed. The variety of
      biological functions attributed to the CCN proteins has led to the proposal of a
      model in which physical interactions between the amino and carboxy portions of
      the CCN proteins modulate their biological activity and ensure a proper balance
      of positive and negative signals through interactions with other partners. In
      this model, disruption of the secondary structure of the CCN proteins induced by
      deletions of either terminus is expected to confer on the truncated polypeptide
      constitutive positive or negative activities.

PMID- 11322168
TI  - Expression profile of human herpesvirus 8 (HHV-8) in pyothorax associated
      lymphoma and in effusion lymphoma.
AB  - AIMS: Pyothorax associated lymphoma (PAL) occurs in a clinical setting of
      longstanding pyothorax or chronic inflammation of the pleura. Like primary
      effusion lymphoma, it has an association with Epstein-Barr virus (EBV), and is
      confined to the pleural cavity, but has differing morphological and phenotypic
      features. Human herpesvirus 8 (HHV-8) has been consistently reported in primary
      effusion lymphoma. This study examines the immunophenotype of two European cases
      of PAL, investigates the presence of HHV-8 and its expression profile, and
      assesses whether PAL is similar to other effusion lymphomas. METHODS: Material
      was obtained from two European cases of PAL. Immunocytochemical analysis was
      performed using antibodies against CD45, CD20, CD79a, CD45RAA, CD3, CD43, CD45RO
      (UCHL1), CD30, BCL-2, CD68, epithelial membrane antigen (EMA), BCL-6, p53, Ki-67,
      kappa light chain, lambda light chain, and the EBV antigens latent membrane
      protein 1 (LMP-1) and EBV encoded nuclear antigen 2 (EBNA-2). The cases were
      examined for HHV-8 by means of polymerase chain reaction in situ hybridisation
      (PCR-ISH), solution phase PCR, in situ hybridisation (ISH), and real time
      quantitative TaqMan PCR to HHV-8 open reading frame 26 (ORF-26) and viral (v)
      cyclin encoding regions. The expression profile of HHV-8 in PAL and in BC-1 and
      BC-3 cells was assessed by RNA TaqMan PCR to the HHV-8 genes encoding v-cyclin, v
      IL-6, and G protein coupled receptor (GPCR). RESULTS: Both cases expressed CD24,
      CD20, CD79a, BCL-2, light chain restriction, and high Ki-67 staining. EBV was
      identified by EBER-ISH in one case. HHV-8 was not identified by solution phase
      PCR, but was detected by PCR-ISH (sensitivity of 1 viral genome copy/cell) in 35%
      of the cells and by TaqMan PCR, which showed 50-100 HHV-8 copies/2,000 cell
      genome equivalents (sensitivity of 1 viral genome in 10(6) contaminating
      sequences). HHV-8 v-IL-6, v-cyclin, and GPCR encoded transcripts were identified
      using RNA TaqMan PCR. v-IL-6 was high in PAL and in BC-1 and BC-3 cells.
      CONCLUSION: The presence of HHV-8 in one of two patients with PAL raises
      interesting questions in relation to the pathobiology of the condition. Clearly,
      the results indicate that HHV-8 is not an obligate pathogen, necessary for the
      effusion phenotype, but might contribute to it by its secretion of specific
      cytokines.

PMID- 11322169
TI  - Recovery efficiences on nucleic acid extraction kits as measured by quantitative
      LightCycler PCR.
AB  - AIMS: To compare the efficiency of five nucleic acid extraction kits for
      processing clinical material for the diagnosis of infection. METHODS: Five
      nucleic acid extraction kits for processing clinical material for the diagnosis
      of infection were compared for their relative efficiencies in purifying and
      recovering either viral DNA or RNA from serum samples. Quantitative polymerase
      chain reaction (PCR) assays for hepatitis B virus (HBV) DNA and hepatitis C virus
      (HCV) RNA were performed on the Light-Cycler instrument to determine the relative
      concentrations of the viral nucleic acids recovered by the various protocols.
      RESULTS: Large differences between kits in recovery efficiencies were observed
      for HBV DNA, with those protocols using enzyme digestion in addition to
      chaotropic solutions performing better than those using chemical disruption
      alone. CONCLUSIONS: There were large differences between the kits and it appeared
      that those extraction kits containing a proteolytic enzyme and carrier nucleic
      acid (and that are supplied RNase free) have the widest potential application in
      the routine microbiology laboratory.

PMID- 11322170
TI  - Disparate E-cadherin mutations in LCIS and associated invasive breast carcinomas.
AB  - AIMS: The relation between lobular carcinoma in situ (LCIS) and invasive breast
      cancer is unresolved. In an attempt to establish whether LCIS is a precursor of
      invasive cancer the mutational status and the expression of E-cadherin was
      analysed in LCIS and associated invasive breast carcinoma in 23 patients.
      METHODS: Foci of LCIS and associated invasive carcinoma were individually
      microdissected from tissue from 23 patients. Exons 4-16 of the E-cadherin gene
      were analysed using single strand conformation polymorphism (SSCP); protein
      expression and the localisation of E-cadherin and beta-catenin were assessed with
      the use of immunohistochemistry. RESULTS: Immunohistochemistry revealed a lack of
      expression of E-cadherin and beta-catenin in most LCIS samples and invasive foci.
      In all but four cases, the staining pattern was identical in the LCIS and
      associated invasive areas. When E-cadherin was absent, beta-catenin was also
      undetected, suggesting a lack of expression of alternative classic cadherin
      members in these lesions. Coincident E-cadherin mutations in LCIS and associated
      invasive carcinoma were not identified in this series of patients. However,
      mutational analysis of E-cadherin in multiple foci of carcinoma in situ
      surrounding an invasive lesion provided evidence to support ductal carcinoma in
      situ as a precursor of invasive ductal carcinoma. CONCLUSION: These data support
      the hypothesis that LCIS is not a precursor of invasive breast carcinoma but a
      marker of increased risk of developing invasive disease.

PMID- 11322171
TI  - Activity of the EBNA1 promoter associated with lytic replication (Fp) in Epstein
      Barr virus associated disorders.
AB  - BACKGROUND/AIMS: In Epstein-Barr virus (EBV) positive cell lines that are stably
      infected, three different promoters are known to direct the transcription of EBV
      nuclear antigen 1 (EBNA1). These are located in the BamHI-C, BamHI-Q, and BamHI-F
      regions of the viral genome (Cp, Qp, and Fp, respectively). Fp is activated upon
      induction of the viral lytic cycle. The aim of this study was to investigate the
      activity of Fp in EBV associated diseases. METHODS: Using reverse transcriptase
      polymerase chain reaction, a qualitative analysis of EBNA1 promoter usage in
      various EBV associated diseases was performed. RESULTS: Fp driven transcription
      was detected in the context of primary infection and/or lytic replication; at
      least a portion of the Fp driven transcripts encoded EBNA1. Qp driven EBNA1
      transcripts were detected in most samples across the range of disorders tested.
      Cp driven EBNA1 transcripts were detected in the context of immune suppression
      and in samples containing EBV positive (non-neoplastic) lymphoid cells.
      CONCLUSIONS: These results confirm the previously proposed "housekeeping"
      function of the Qp promoter.

PMID- 11322172
TI  - Aluminium toxicokinetics: an updated minireview.
AB  - This MiniReview updates and expands the MiniReview of aluminium toxicokinetics by
      Wilhelm et al. published by this journal in 1990. The use of 26Al, analyzed by
      accelerator mass spectrometry, now enables determination of Al toxicokinetics
      under physiological conditions. There is concern about aluminium in drinking
      water. The common sources of aluminium for man are reviewed. Oral Al
      bioavailability from water appears to be about 0.3%. Food is the primary common
      source. Al bioavailability from food has not been adequately determined.
      Industrial and medicinal exposure, and perhaps antiperspirant use, can
      significantly increase absorbed aluminium. Inhalation bioavailability of airborne
      soluble Al appears to be about 1.5% in the industrial environment. Al may
      distribute to the brain from the nasal cavity, but the significance of this
      exposure route is unknown. Systemic Al bioavailability after single underarm
      antiperspirant application may be up to 0.012%. All intramuscularly injected Al,
      e.g. from vaccines, may eventually be absorbed. Al distributes unequally to all
      tissues. Distribution and renal excretion appear to be enhanced by citrate. Brain
      uptake of Al may be mediated by Al transferrin and Al citrate complexes. There
      appears to be carrier-mediated efflux of Al citrate from the brain. Elimination
      half-lives of years have been reported in man, probably reflecting release from
      bone. Al elimination is primarily renal with < or = 2% excreted in bile. The
      contribution of food to absorbed Al needs to be determined to advance our
      understanding of the major components of Al toxicokinetics.

PMID- 11322173
TI  - Role of humoral mediators in, and influence of a liposomal formulation on, acute
      amphotericin B nephrotoxicity.
AB  - The mechanisms responsible for amphotericin B nephrotoxicity remain incompletely
      understood, but clearly involve reduction in renal blood flow and glomerular
      filtration rate. Both direct effects of amphotericin B on contractile vascular
      cells, and indirect effects, due to humoural mediators, have been proposed. This
      study examines the role of nitric oxide, endothelin and angiotensin II in the
      acute nephrotoxic effects of amphotericin B in rats, and compares the anti-fungal
      and nephrotoxic effects of liposomal amphotericin B and amphotericin B
      deoxycholate. Anaesthetized rats were given infusions of amphotericin B
      deoxycholate in the presence or absence of N-nitro-L-arginine, PD 145065, a non
      specific endothelin receptor antagonist, and L-158809, an angiotensin II type I
      receptor antagonist, or increasing doses of liposomal amphotericin B.
      Amphotericin B-deoxycholate (0.03 mg/kg/min intravenously) caused a significant
      44% reduction in glomerular filtration rate and 65% maximal fall in renal blood
      flow. N-Nitro-L-arginine-treated rats had a lower renal blood flow and glomerular
      filtration rate at baseline, but sustained similar reduction of 53% and 75% in
      these parameters, respectively. PD145065 and L-158809 did not modify these
      effects either. Increasing doses of liposomal amphotericin B (from 0.01 up to
      0.50 mg/kg/min.) induced no change in either glomerular filtration rate or renal
      blood flow. In vitro susceptibility tests revealed similar potency for liposomal
      amphotericin B and amphotericin B-deoxycholate in their fungistatic effects and
      slightly higher potency for amphotericin B-deoxycholate in their fungicidal
      effect. These results suggest that endogenous endothelin, angiotensin II or
      nitric oxide systems are not involved in the nephrotoxic effects of amphotericin
      B. The liposomal amphotericin B results suggest that amphotericin B
      nephrotoxicity is due to a direct interaction of amphotericin B with renal cells
      that is prevented by its encapsulation in liposomes.

PMID- 11322174
TI  - Rat liver microsomal lipid peroxidation produced during the oxidative metabolism
      of ethacrynic acid.
AB  - Thiobarbituric acid reactive substances (TBARS) were produced in rat liver
      microsomal suspension incubated with ethacrynic acid (loop diuretic drug) and
      NADPH. Two oxidative metabolites of ethacrynic acid with dicarboxylic acid and
      hydroxylated ethyl group, respectively, were formed in the reaction mixture. The
      oxidative metabolism of ethacrynic acid was inhibited by cytochrome P450
      inhibitors. The formation of TBARS was remarkably depressed by inhibitors like
      diethyldithiocarbamate and disulfiram. These results indicate that lipid
      peroxidation occurred in rat liver microsomes through the oxidative metabolism of
      ethacrynic acid.

PMID- 11322175
TI  - Antiplatelet mechanism of 2-chloro-3-(4-hexylphenyl)-amino-1,4-naphthoquinone
      (NQ304), an antithrombotic agent.
AB  - The effects of 2-chloro-3-(4-hexylphenyl)-amino-1,4-naphthoquinone (NQ304), an
      antithrombotic agent, on aggregation, binding of fibrinogen to glycoprotein
      IIb/IIIa and intracellular signals were investigated using human platelets. NQ304
      inhibited thrombin-, arachidonic acid- and thapsigargin-induced aggregation of
      washed human platelets with the IC50 values of 22.2+/-0.7, 6.5+/-0.2, and 7.6+/
      0.1 microM, respectively. NQ304 significantly inhibited fluorescein
      isothiocyanate-conjugated fibrinogen binding to human platelet surface
      glycoprotein IIb/IIIa receptor by 75%, but failed to inhibit the fibrinogen
      binding to purified glycoprotein IIb/IIIa receptor. This result suggests that
      NQ304 inhibit platelet aggregation by suppression of an intracellular pathway
      that involves exposure of the glycoprotein IIb/IIIa receptor, rather than by
      direct inhibition of fibrinogen-glycoprotein IIb/IIIa binding. NQ304
      significantly inhibited thrombin-induced increase in intracellular Ca2+
      mobilization at the dose of 30 microM and ATP secretion in a dose-dependent
      manner. It also inhibited thrombin- and arachidonic acid-induced thromboxane A2
      formation in human platelet dose-dependently. In conclusion, the antiplatelet
      mechanism of NQ304 may be due to the reduction of the thromboxane A2 formation,
      inhibition of adenosine triphosphate release and intracellular calcium
      mobilization.

PMID- 11322176
TI  - Effect of clarithromycin and itraconazole on the pharmacokinetics of ropivacaine.
AB  - In a double-blind, randomised, three-way cross-over study, eight healthy
      volunteers ingested daily for 4 days either 250 mg clarithromycin twice daily,
      200 mg itraconazole once daily, or placebo. On day 4, each subject received a
      single dose of 0.6 mg kg-1 ropivacaine intravenously over 30 min. Ropivacaine and
      (S)-2',6'-pipecoloxylidide in venous plasma and urine samples were measured for
      up to 12 hours and 24 hours, respectively. There were no significant changes in
      the pharmacokinetic parameters of the parent ropivacaine after ingestion of
      clarithromycin or itraconazole. However, the peak plasma concentration and AUC of
      (S)-2',6'-pipecoloxylidide metabolite were significantly decreased in both the
      clarithromycin and itraconazole phases, compared with the placebo phase. The
      fraction of ropivacaine metabolised to (S)-2',6'-pipecoloxylidide excreted in
      urine was decreased in the itraconazole phase. Both clarithromycin and
      itraconazole inhibit the CYP3A4 mediated formation of (S)-2',6'-pipecoloxylidide
      from ropivacaine. With the doses used, itraconazole is a stronger inhibitor than
      clarithromycin. The interaction of clarithromycin with ropivacaine seems to be
      dose (concentration)-dependent.

PMID- 11322178
TI  - L-cysteine and sodium hydrosulphide inhibit spontaneous contractility in isolated
      pregnant rat uterine strips in vitro.
AB  - The control of myometrial contractility during pregnancy and parturition is not
      fully understood. Gas signalling molecules, such as nitric oxide and carbon
      monoxide, have been shown to relax the myometrium and may be involved in the
      control of contractility. Hydrogen sulphide has recently been shown to be
      produced endogenously in animal and human tissue and to have a signalling
      function. The aim of the study was to investigate the effect of L-cysteine and
      sodium hydrosulphide, potential hydrogen sulphide donors, on pregnant rat uterine
      contractility in vitro. Strips of pregnant rat uterus (n=22) were set up in a
      standard organ bath system. Following equilibration and recording of spontaneous
      contractility, the tissue was exposed to 45 mM potassium chloride followed by 1
      nM oxytocin. Dose ranges of 10(-8) - 10(-3) M of L-cysteine (n=8) or sodium
      hydrosulphide (n=8) were subsequently applied to the tissue. In a third series of
      experiments (n=6) the effect of doses of 10(-9), 10(-6) and 10(-3) M of L
      cysteine, D-cysteine, L-serine, DL-methionine and DL-homocysteine on myometrial
      contractility were compared. Contractions were integrated over 10 min. periods
      and the values were compared by one-way analysis of variance. L-Cysteine and
      sodium hydrosulphide produced significant dose-dependent decreases in uterine
      spontaneous contractility. Of the amino acids tested, only L-cysteine produced a
      significant reduction in spontaneous contractility at a dose of 10(-3) M. This
      study has demonstrated novel tocolytic actions of L-cysteine and sodium
      hydrosulphide, however further work is required to determine their mechanisms of
      action.

PMID- 11322177
TI  - Bioactivation and cytotoxicity of 1,1-dichloro-2,2,2-trifluoroethane (HCFC-123)
      in isolated rat hepatocytes.
AB  - The bioactivation and cytotoxicity of 1,1-dichloro-2,2,2-trifluoroethane (HCFC
      123), a replacement for some ozone-depleting chlorofluorocarbons, were
      investigated using freshly isolated hepatocytes from non-induced male rats. A
      time- and concentration-dependent increase in the leakage of lactate
      dehydrogenase and a concentration-dependent loss of total cellular glutathione
      were observed in cells incubated with 1, 5 and 10 mM HCFC-123 under normoxic or
      hypoxic (about 4% O2) conditions. Lactate dehydrogenase leakage was completely
      prevented by pretreating the cell suspension with the free radical trapper N-t
      butyl-alpha-phenylnitrone. The aspecific cytochrome P450 (P450) inhibitor,
      metyrapone, totally prevented the lactate dehydrogenase leakage from hepatocytes,
      while two isoform-specific P450 inhibitors, 4-methylpyrazole and troleandomycin
      (a P450 2E1 and a P450 3A inhibitor, respectively), provided a partial protection
      against HCFC-123 cytotoxicity. Interestingly, pretreatment of cells with
      glutathione depletors, such as phorone and diethylmaleate, did not enhance the
      HCFC-123-dependent lactate dehydrogenase leakage. Two stable metabolites of HCFC
      123, 1-chloro-2,2,2-trifluoroethane and 1-chloro-2,2-difluoroethene, were
      detected by gas chromatography/mass spectrometry analysis of the head space of
      the hepatocyte incubations carried out under hypoxic and, although at a lower
      level, also normoxic conditions, indicating that reductive metabolism of HCFC-123
      by hepatocytes had occurred. The results overall indicate that HCFC-123 is
      cytotoxic to rat hepatocytes under both normoxic and hypoxic conditions, due to
      its bioactivation to reactive metabolites, probably free radicals, and that P450
      2E1 and, to a lower extent, P450 3A, are involved in the process.

PMID- 11322179
TI  - Short-term effects of four antibiotics on DNA synthesis in endothelial cells.
AB  - The irritating effect of parenterally administered antibiotics on vessels is a
      common clinical problem. In a previous study we found that solutions of three
      commonly used antibiotics, cefuroxime, erythromycin and dicloxacillin, exerted
      cytotoxic effects on endothelial cells after 24 hr exposure. In contrast
      benzylpenicillin did not have such effects. In the present study, endothelial
      cells of different origin were exposed to these four antibiotics at higher
      concentrations than in the previous investigation but only for 5, 30 and 60 min.
      Incorporation of 3H-thymidine in the cells as a measurement of DNA synthesis was
      used as cytotoxic assay. A concentration-dependent and time-related inhibition
      was found after exposure to erythromycin and dicloxacillin but not after exposure
      to cefuroxime and benzylpenicillin. The effects were similar on the three
      different cell types used in the experiments. This study demonstrates that the
      cytotoxic effects differ even after short-term exposure to the antibiotics. In
      contrast to the previous study, cefuroxime lacks cytotoxicity when endothelial
      cells are exposed for less than one hour. The short-term exposition model used in
      this study should be more predictive as it mimics in vivo conditions better.

PMID- 11322180
TI  - Toxic effects of sarin in rats at three months following single or repeated low
      level inhalation exposure.
AB  - Male albino Wistar rats were once or repeatedly exposed to three various low
      concentrations of sarin for 60 min. in the inhalation chamber. The clinical
      status of control as well as sarin-poisoned rats was tested 3 months after
      exposure to sarin using biochemical, haematological, neurophysiological,
      behavioural and immunotoxicological methods. While biochemical and haematological
      parameters, including the activities of cholinesterases in erythrocytes, plasma
      and various organs (brain, diaphragm), did not differ from the control values
      regardless of the sarin concentration used, few signs of sarin-induced
      neurotoxicity and immunotoxicity in sarin-poisoned rats were demonstrated. This
      was especially true when the single exposure of rats to non-convulsive
      symptomatic concentration and repeated exposure of rats to clinically
      asymptomatic concentration of sarin was used. In rats repeatedly poisoned with
      clinically asymptomatic concentrations of sarin, the alteration of the gait
      characterized by ataxia, the increase in the stereotyped behaviour, the increase
      in the excitability of the central nervous system following the administration of
      the convulsive drug pentamethylenetetrazol were observed. In rats poisoned with
      non-convulsive symptomatic concentration of sarin, the subtle supression of
      spontaneous, as well as lipopolysaccharides-stimulated, proliferation of spleen
      lymphocytes and the bactericidal activity of peritoneal macrophages was primarily
      observed besides the signs of neurotoxicity. Our findings confirm that both non
      convulsive symptomatic and clinically asymptomatic concentrations of sarin can
      only cause very few, subtle long-term signs of neurotoxicity and immunotoxicity
      in sarin-poisoned rats when the rats were exposed to asymptomatic sarin
      concentrations repeatedly.

PMID- 11322181
TI  - Pharmacological properties of cannabinoid receptors in the avian brain:
      similarity of rat and chicken cannabinoid1 receptor recognition sites and
      expression of cannabinoid2 receptor-like immunoreactivity in the embryonic chick
      brain.
AB  - The pharmacological properties of brain cannabinoid receptors were investigated
      in brains of 35 day-old chickens, since little is known about the avian
      cannabinoid system. The cannabinoid1 receptor-selective antagonist ligand [3H]SR
      141716A bound to chicken brain membranes with K(D) and Bmax values of 0.92+/-0.28
      nM and 790+/-58 fmol/mg protein, respectively. The binding was inhibited by CP
      55,940 with a pI50 value of 7.63+/-0.14 and by a series of compounds with the
      order of potency CP 55,940>R(+)WIN 55,212-2>R-1 methanandamide approximately DAK.
      S(-)WIN 55,212-3 and AM404 were without inhibitory effect at 1 microM. Similar
      results were found for rat brain membranes. For both rat and chicken brain
      membranes, addition of the non-hydrolysable GTP analogues Gpp[NH]p and GTPgammaS
      shifted the CP 55,940 inhibition curve to the right, consistent with an intact
      coupling to G-proteins in the preparations. Fatty acid amidohydrolase in chicken
      brain membranes was less sensitive to inhibition by phenylmethylsulphonyl
      fluoride and arachidonoyl serotonin than its rodent equivalent. However, when
      fatty acid amidohydrolase activity in the preparations was reduced by use of a
      lower assay membrane concentration, anandamide was found to inhibit the binding
      of [3H]SR 141716A to chicken membranes with a pI50 value of 6.39+/-0.16. Using a
      novel antibody raised to amino acids 346-359 from the C-terminal tail of the
      human cannabinoid2 receptor, it was found that embryonic chick brain tissue (and
      embryonic chick neurones in primary culture) expressed a approximately 53 kDa
      immunoreactive band. This immunoreactivity, which was prevented by preincubation
      of the antibody with the immunising peptide, was also seen in cells expressing
      the recombinant human cannabinoid, receptor, but was not seen in adult chicken
      brain homogenates or in rat cerebellar homogenates. However, a "classical"
      cannabinoid2-receptor component of [3H]WIN 55212-2 binding (i.e. a fraction
      inhibited by low concentrations of the cannabinoid2-receptor-selective antagonist
      SR 144528) was not found.

PMID- 11322182
TI  - A study of light-induced proton transfer from gas phase (radical) cations to
      reference bases. Bracketing of proton transfer from excited ions and associated
      reaction kinetics.
AB  - By use of Fourier transform ion cyclotron resonance, it is shown that protonated
      naphthalene when excited with laser light of 488 nm is more reactive in proton
      transfer to reference bases than in its ground state. The excitation leads to
      reaction with bases for which proton transfer in the ground state is endothermic
      up to a detected maximum of 60 kJ/mol. For indene radical cations excited at
      514.5 nm, it is shown that the rate constant for proton transfer to 3-pentanone
      is either about 10 or about 100 times lower than the rate constant for relaxation
      by collisions with 3-pentanone. From the energy deposited in the ions, 0.5-0.6 eV
      is available for proton transfer to a base which seems reasonable when taking
      into account a complete randomization of the initially deposited energy.

PMID- 11322183
TI  - Reactions of atomic transition-metal ions with long-chain alkanes.
AB  - Understanding metal ion interactions with long-chain alkanes not only is of
      fundamental importance in the areas of organometallic chemistry, surface
      chemistry, and catalysis, but also has significant implication in mass
      spectrometry method development for the analysis of polyethylene. Polyethylene
      represents one of the most challenging classes of polymers to be analyzed by mass
      spectrometry. In this work, reactions of several transition-metal ions including
      Cr+, Mn+, Fe+, Co+, Ni+, Cu+, and Ag+ with long-chain alkanes, C28H58 and C36H74,
      are reported. A metal powder and the nonvolatile alkane are co-deposited onto a
      sample target of a laser desorption/ionization (LDI) time-of-flight mass
      spectrometer. The metal ions generated by LDI react with the vaporized alkane
      during desorption. It is found that all these metal ions can form adduct ions
      with the long-chain alkanes. Fe+, Co+, and Ni+ produce in-source fragment ions
      resulting from dehydrogenation and dealkylation of the adduct ions. The post
      source decay (PSD) spectra of the metal-alkane adduct ions are recorded. It is
      shown that PSD of Ag+ alkane adduct ions produces bare metal ions only,
      suggesting weak binding between this metal ion and alkane. The PSD spectra of the
      Fe+, Co+, and Ni+ alkane adduct ions display extensive fragmentation. Fragment
      ions are also observed in the PSD spectra of Cr+, Mn+, and Cu+ alkane adduct
      ions. The high reactivity of Fe+, Co+, and Ni+ is consistent with that observed
      in small alkane systems. The unusually high reactivity of Cr+, Mn+, and Cu+ is
      rationalized by a reaction scheme where a long-chain alkane first forms a complex
      with a metal ion via ion/induced dipole interactions. If sufficient internal
      energy is gained during the complex formation, metal ions can be inserted into C
      H and C-C bonds of the alkane, followed by fragmentation. The thermal energy of
      the neutral alkane is believed to be the main source of the internal energy
      acquired in the complex. Finally, the implication of this work on mass
      spectrometry method development for polyethylene analysis is discussed.

PMID- 11322184
TI  - Product ion studies of diastereomeric benzo[ghi]fluoranthene tetraols by matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry and post
      source decay.
AB  - The product ion formation characteristics of the four diastereomeric tetrahydroxy
      benzo[ghi]fluoranthene compounds formed by hydrolysis of the syn and anti
      diastereomers of trans-3,4-dihydroxy-5,5a-epoxy-3,4,5,5a
      tetrahydrobenzo[ghi]fluoranthene are studied using matrix-assisted laser
      desorption/ionization and post-source decay (PSD) to determine a correlation
      between the fragmentation characteristics of these tetraols and the structures of
      the diol-epoxide diastereomers from which they are hydrolyzed. The tetraols
      formed by the trans ring opening of the diol epoxides during hydrolysis yield
      product ion spectra specific for the syn and anti configurations of their
      precursor diol epoxides. All four diastereomeric tetraols form product ions by
      the losses of one and/or two water molecules in varying proportions when lithium
      cationized molecule ions (m/z 301) are selected for PSD product ion analysis. The
      differences in the PSD spectra of these four Li+-cationized molecules are
      rationalized in terms of a water loss mechanism that involves the 1,2 elimination
      of a hydrogen atom and hydroxyl group that are cis with respect to each other on
      adjacent carbons.

PMID- 11322185
TI  - Mass spectral fragmentation reactions of a therapeutic 4-azasteroid and related
      compounds.
AB  - Mass spectra were acquired for a therapeutic 4-azasteroid (dutasteride), and some
      related compounds, using various ionization conditions (EI, CI, APCI and ESI) in
      both positive and negative ion modes. The ionization and fragmentation behavior
      of the compound dutasteride, its precursors and several analogs is reported.
      Positive atmospheric pressure chemical ionization (APCI+) and positive
      electrospray ionization (ESI+) produced distinctive collision-induced
      dissociation (CID) spectra for the respective [MH]+ ions of dutasteride. The
      spectral differences are attributed to ion populations having either different
      structures or different internal energy distributions (as a consequence of the
      method of ionization). Irrespective of their origin, the protonated molecules
      undergo interesting fragmentation reactions when collisionally activated. The
      identity of the major fragmentation products was confirmed by accurate mass
      measurement. The negative APCI mass spectrum of dutasteride displays extensive
      dehydrohalogenation, apparently due to the thermal component of the APCI process.
      Some of the resulting radical anions display remarkable stability toward
      collisional decomposition. Details of the fragmentation behavior for the negative
      ion species and their relationship to the positive ion results are discussed.

PMID- 11322186
TI  - Mass spectrometric evidence for mechanisms of fragmentation of charge-derivatized
      peptides.
AB  - Mass spectrometry of charged derivatives of peptides has been a growing area of
      interest in the past decade. Fragmentation of charged derivatives of peptides is
      believed to be different from than that of protonated peptides when analyzed by
      collisionally activated dissociation-tandem mass spectrometry (CAD-MS/MS). The
      charged derivatives fragment by charge-remote fragmentation mechanisms, which are
      usually classified as high-energy (HE)-CAD processes. Our objective in the
      present study is to investigate the mechanism of fragmentation of charged
      derivatives of peptides when analyzed by matrix-assisted laser
      desorption/ionization-postsource decay-mass spectrometry (MALDI-PSD-MS) and
      electrospray ionization (ESI)-CAD-MS/MS (ion trap), which involve low-energy
      processes. Three major types of hydrogens (alpha, beta, and amide) are available
      for migration during the formation of the *a(n) ions (the predominant ion series
      produced from these charged derivatives). To pinpoint which of the three
      hydrogens is involved in the formation of the *a(n) ions, deuterium-labeled
      peptide derivatives with labels at specific sites were synthesized and analyzed
      by MALDI-PSD-MS and ESI-CAD-MS/MS. Our results suggest that the amide hydrogen of
      the residue at which the cleavage occurs shifts during the formation of *a(n);
      this observation serves as evidence for the mechanism proposed earlier by Liao et
      al. for fragmentation of such charged derivatives. The results also help
      elucidate the structure of the *a(n) ions, *b(n) ions, and others formed during
      cleavage at the proline residue, as well as the ions formed during loss of the C
      terminal residue from these charged derivatives.

PMID- 11322187
TI  - Inter- and intra-molecular migration of peptide amide hydrogens during
      electrospray ionization.
AB  - The isotopic exchange of amide hydrogens in proteins in solution strongly depends
      on the surrounding protein structure, thereby allowing structural studies of
      proteins by mass spectrometry. However, during electrospray ionization (ESI), gas
      phase processes may scramble or deplete the isotopic information. These processes
      have been investigated by on-line monitoring of the exchange of labile deuterium
      atoms in homopeptides with hydrogens from a solvent suitable for ESI. The
      relative contribution of intra- and inter-molecular exchange in the gas phase
      could be studied from their distinct influence on the well-characterized exchange
      processes in the spraying solution. The deuterium content of individual labile
      hydrogens was assessed from the isotopic patterns of two consecutive collision
      induced dissociation fragments, as observed with a 9.4 T Fourier transform ion
      cyclotron resonance (FTICR) mass spectrometer. Results demonstrate that gas phase
      exchange in the high-pressure region between the capillary and the skimmer cause
      substantial depletion of the isotopic information of penta-phenylalanine and
      penta-aspartic acid. For penta-alanine and hexa-tyrosine, the amide hydrogens
      located close to the N-terminus are depleted from deuterium during mass analysis.
      Amide hydrogens located close to the C-terminus still retain the information of
      the isotopic state in solution, but they are redistributed by intra-molecular
      exchange of the amide hydrogens with the C-terminal hydroxyl group.

PMID- 11322188
TI  - In-source decay characteristics of peptides in matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry.
AB  - In-source decay (ISD) of peptides, coupled with matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry, has been examined to
      determine the influence of the matrix, the susceptibility of amino-acid residues
      to ISD, and the effect of extraction delay times. Out of nine di- and tri
      hydroxybenzoic acids and three cinnamic derivatives tested, the most suitable
      matrix for ISD was 2,5-dihydroxybenzoic acid. The amine bond at Xxx-Gly and Xxx
      Val residues was less susceptible than other amino-acid residues to ISD; however,
      the more sensitive residue(s) were not as clear. Using a peptide that gave the
      y(n)- and (z(n) + 2)-series product ions, it was confirmed that amide-bond
      cleavage (formation of the y(n)-series ions) accompanied metastable peaks,
      whereas metastable peaks were never observed with amine-bond cleavage [formation
      of the (z(n) + 2)-series ions]. Furthermore, abundant c(n)-series ions, which
      originate from amine-bond cleavage on the peptide backbone, were observed
      whenever a minimum delay time of 38 ns or continuous extraction was used to
      obtain spectra. These data indicate that amine-bond cleavage in ISD takes place
      on the ionization time scale before the energy randomization is completed.

PMID- 11322189
TI  - An electrospray ionization mass spectrometry investigation of 1-anilino-8
      naphthalene-sulfonate (ANS) binding to proteins.
AB  - The binding of 1-anilino-8-naphthalene-sulfonic acid (ANS) to various globular
      proteins at acidic pH has been investigated by electrospray ionization mass
      spectrometry (ESI-MS). Maximal ANS binding is observed in the pH range 3-5. As
      many as seven species of dye-bound complexes are detected for myoglobin. Similar
      studies were carried out with cytochrome c, carbonic anhydrase, triosephosphate
      isomerase, lysozyme, alpha-lactalbumin, and bovine pancreatic trypsin inhibitor
      (BPTI). Strong ANS binding was observed wherever molten globule states were
      postulated in solution. ANS binding is not observed for lysozyme and BPTI, which
      have tightly folded structures in the native form. Alpha-lactalbumin, which is
      structurally related to lysozyme but forms a molten globule at acidic pH,
      exhibited ANS binding. Reduction of disulfide bonds in these proteins leads to
      the detection of ANS binding even at neutral pH. Binding was suppressed at very
      low pH (<2.5), presumably due to neutralization of the charge on the sulfonate
      moiety. The distribution of the relative intensities of the protein bound ANS
      species varies with the charge state, suggesting heterogeneity of gas phase
      conformations. The binding strength of these complexes was qualitatively
      estimated by dissociating them using enhanced nozzle skimmer potentials. The
      skimmer voltages also affected the lower and higher charge states of these
      complexes in a different manner.

PMID- 11322190
TI  - Analysis of peptides and proteins containing nitrotyrosine by matrix-assisted
      laser desorption/ionization mass spectrometry.
AB  - Oxidative damage to proteins can occur under physiological conditions through the
      action of reactive oxygen species, including those containing nitrogen such as
      peroxynitrite (ONO2-). Peroxynitrite has been shown in vitro to target tyrosine
      residues in proteins through free radical addition to produce 3-nitrotyrosine. In
      this work, we show that mass spectral patterns associated with 3-nitrotyrosine
      containing peptides allow identification of peptides containing this
      modification. Matrix-assisted laser desorption/ionization (MALDI) mass
      spectrometry was used to characterize a synthetic peptide AAFGY(m-NO2)AR and
      several peptides containing 3-nitrotyrosine derived from bovine serum albumin
      treated with tetranitromethane. A unique series of ions were found for these
      peptides in addition to the mass shift of +45 Da corresponding to the addition of
      the nitro group. Specifically, two additional ions were observed at roughly equal
      abundance that correspond to the loss of one and two oxygens, and at lower
      abundances, two ions are seen that suggest the formation of hydroxylamine and
      amine derivatives. These latter four components appear to originate by laser
      induced photochemical decomposition. MALDI-MS analysis of the synthetic peptide
      containing 3-nitrotyrosine revealed this same pattern. Post-source decay (PSD)
      MALDI-time-of-flight (TOF) and collisional activation using a prototype MALDI
      quadrupole TOF yielded extensive fragmentation that allowed site-specific
      identification of 3-nitrotyrosine. Conversion of peptides containing 3
      nitrotyrosine to 3-aminotyrosine with Na2S2O4 yielded a single molecular ion by
      MALDI with an abundant sidechain loss under PSD conditions. These observations
      suggest that MALDI can provide a selective method for the analysis and
      characterization of 3-nitrotyrosine-containing peptides.

PMID- 11322191
TI  - Analysis of diacyl peroxides by Ag+ coordination ionspray tandem mass
      spectrometry: free radical pathways of complex decomposition.
AB  - Organic peroxides have significance in organic synthesis and biological
      processes. Characterization of these compounds with weak O-O bonds is sometimes
      difficult due to their thermal instability and sensitivity to acid or base.
      Coordination of diacyl peroxides with AgBF4 provides a means for analysis of
      these compounds by coordination ionspray tandem mass spectrometry (CIS-MS/MS).
      Precursor ion (Q1) scans of acetyl benzoyl peroxide give two Ag+ adducts, [M + Ag
      + solvent]+ and [M + Ag + M]+. These silver ion adducts can be selectively
      dissociated (CID) to give unique structural information about the analyte.
      Decomposition of the [M + Ag + solvent]+ adduct generates fragmentation products
      due to apparent homolytic cleavage of the O-O bond followed by decarboxylation of
      the resultant radicals. The bis-diacylperoxide complex, [M + Ag + M]+ gives CID
      pathways that involve homolysis of the (O-O bond and free radical cross-coupling
      of the two diacyl peroxides coordinated to the silver ion, i.e. formation of
      dibenzoyl peroxide, phenyl benzoate, and biphenyl from acetyl benzoyl peroxide.
      The observation of free radical CID modes is uncommon in mass spectrometry but
      these pathways are consistent with well-known solution and gas phase processes
      for peroxide compounds. The proposed fragmentation pathways have been supported
      by experiments with (18)O and deuterated substrates. This technique can be
      applied to analyze diacyl peroxides with different substituents as well.

PMID- 11322192
TI  - 5-Methoxysalicylic acid and spermine: a new matrix for the matrix-assisted laser
      desorption/ionization mass spectrometry analysis of oligonucleotides.
AB  - 5-Methoxysalicylic acid (MSA) is demonstrated to be a useful matrix for matrix
      assisted laser desorption/ionization time-of-flight (TOF) mass spectrometry of
      oligonucleotides, when desorption/ionization without fragmentation is desired.
      When MSA is combined with the additive spermine, the need for desalting is
      reduced. The MSA/spermine matrix yields linear TOF mass spectra with improved
      resolution, less fragmentation, and less intense alkali ion adduct peaks than
      those spectra obtained using 3-hydroxypicolinic acid and 6-aza-2-thiothymine with
      spermine or diammonium hydrogen citrate as additives. Instrumental conditions are
      discussed to improve the spectral resolution, specifically the use of longer
      delay times in the delayed-extraction ion source.

PMID- 11322193
TI  - Microfabricated PDMS multichannel emitter for electrospray ionization mass
      spectrometry.
AB  - A novel microfabricated multichannel emitter for electrospray ionization mass
      spectrometry (ESI-MS) was implemented with polydimethylsiloxane (PDMS) using a
      soft lithography technique. The emitters are formed as electrospray tips along a
      thin membrane on the edge of the device with channels of 100 microm x 30 microm
      dimensions. The electrospray performance of the PDMS emitters for a single
      channel device and a four channel device interfaced with a time-of-flight mass
      spectrometer was evaluated for detecting the molecular weight of reference
      peptides (angiotensin I and bradykinin). The emitters were durable at the flow
      rate of 1-20 microL min(-1) for more than 30 h of continuous electrospray with
      limit of detection of 1 microM (S/N 18). This microfabrication method for a PDMS
      multichannel emitter as an integral part of a microfluidic device will facilitate
      development of more complex microfluidic analysis systems using ESI-MS.

PMID- 11322194
TI  - Fragmentation of a novel marine peptide, plicatamide, involves an unusual gas
      phase intramolecular rearrangement.
AB  - During our characterization of plicatamide 1, a modified octapeptide: Phe-Phe-His
      Leu-His-Phe-His-dc deltaDOPA (where dc deltaDOPA = decarboxy-(E)-alpha,beta
      dehydro-3,4-dihydroxyphenylalanine) from the blood cells of the ascidian Styela
      plicata, we noted a series of fragment ions from the [M + H]+ ion which could not
      be assigned. There was no evidence in the 1H NMR spectrum to support an
      alternative molecular structure and the series of fragment ions were not present
      in the tandem mass spectrometry analysis of the [M + Na]+ ion. In addition, there
      was no evidence that the sample was a mixture of isobaric compounds. We propose
      that an unusual C-terminal to N-terminal rearrangement is responsible for the
      series of fragment ions from the [M + H]+ ion. This rearrangement was not
      observed in peptide analogs of plicatamide which did not contain the dc deltaDOPA
      at the C-terminus suggesting that this moiety is critical for the rearrangement.
      The proposed reaction is analogous to that recently reported by Vachet et al.
      involving a fragment ion formed from leucine enkephalin.

PMID- 11322195
TI  - Biliary dysplasia as a marker of cholangiocarcinoma in primary sclerosing
      cholangitis.
AB  - BACKGROUND/AIMS: Indentification of biliary dysplasia in a primary sclerosing
      cholangitis (PSC) liver biopsy may indicate developing cholangiocarcinoma. The
      objectives were to determine whether biliary dysplasia can be recognised
      reproducibly in PSC and to compare the frequency in cases with and without
      cholangiocarcinoma. METHODS: Liver biopsies from 26 PSC cases with concurrent or
      subsequent cholangiocarcinoma (within 2 years) were assessed for biliary
      dysplasia independently by three liver pathologists. This was done in two stages:
      initially, without agreement on criteria, and subsequently after such agreement.
      Liver biopsies from 60 PSC cases without cholangio-carcinoma were also assessed.
      RESULTS: Reproducibility for biliary dysplasia without prior agreement on
      criteria was only marginally better than random (kappa=0.129). In contrast, after
      prior agreement on criteria, reproducibility was moderate (kappa=0.44). Biliary
      dysplasia was agreed to be present by all three pathologists in 23% and 19% of
      biopsies in the first and second round, respectively, from patients with
      cholangiocarcinoma, but in none of the patients without cholangiocarcinoma.
      CONCLUSION: Criteria for biliary dysplasia can be agreed and the entity
      recognised in liver biopsies. The strong association of biliary dysplasia with
      cholangiocarcinoma in PSC suggests use of dysplasia as a marker for current or
      developing malignancy.

PMID- 11322196
TI  - Autoantibodies against nuclear pore complexes are associated with more active and
      severe liver disease in primary biliary cirrhosis.
AB  - BACKGROUND/AIMS: Antibodies against nuclear pore complexes (NPCs) have been
      detected in primary biliary cirrhosis (PBC), but their clinical relevance is
      still unsettled. METHODS: We tested sera from 171 consecutive PBC patients and
      230 control subjects (149 with autoimmune or viral liver diseases, 28 with
      systemic lupus erythematosus, and 53 healthy) by immunoblotting for antibodies
      against purified human NPCs. RESULTS: Antibodies to NPCs were detected in 27% of
      the patients with PBC, were highly specific (97%), and were not associated with
      antimitochondrial antibodies. Their prevalence was higher in symptomatic patients
      (36 vs. 16%, P < 0.01) and was associated (P < 0.001) with more severe disease,
      as assessed by the presence of cirrhosis or its complications (13% prevalence in
      patients without cirrhosis, 31% in uncomplicated, and 54% in complicated
      cirrhosis), or by the application of the Mayo prognostic model (12% in the
      lowest, 21% in the median, 47% in the highest score tertile). Positive patients
      had higher levels of serum bilirubin (2.2 +/- 3.7 vs. 1.0 +/- 1.1 mg/dl, P <
      0.01) and more marked inflammatory infiltrates on liver biopsy (P < 0.05).
      CONCLUSIONS: Autoantibodies to NPCs are more prevalent in PBC patients than in
      controls and are strongly associated with more active and severe disease.

PMID- 11322197
TI  - Postprandial middle cerebral arterial vasoconstriction in cirrhotic patients. A
      placebo, controlled evaluation.
AB  - BACKGROUND/AIMS: The objective of this study was to determine whether cerebral
      arterial vasoconstriction occurs in relation to postprandial splanchnic blood
      pooling in cirrhotic patients. METHODS: The pulsatility and the resistive indexes
      and blood flow in the middle cerebral artery were measured by magnetic resonance
      imaging in 21 cirrhotics and 14 controls. These measurements were repeated 30 min
      after ingestion of a 400 kcal liquid meal or placebo. Seven controls and 14
      patients received the meal, and seven controls and seven patients received
      placebo. RESULTS: In the fasting conditions, cirrhotics had a greater pulsatility
      index (0.81 +/- 0.10 vs. 0.67 +/- 0.05, P < 0.001) and a greater resistive index
      (0.61 +/- 0.04 vs. 0.53 +/- 0.04, P < 0.001) and a lower blood flow (127 +/- 42
      ml/min vs. 167 +/- 37 ml/min, P < 0.03) in the middle cerebral artery compared
      with controls. Meal ingestion significantly increased the pulsatility index (P <
      0.03) and the resistive index (P < 0.01) and decreased blood flow (P < 0.03) in
      the middle cerebral artery in cirrhotics but not in controls. In contrast,
      placebo ingestion had no effect on the hemodynamic parameters in the middle
      cerebral artery in the two groups. CONCLUSIONS: Results support the hypothesis
      that middle cerebral arterial vasoconstriction seen in cirrhotic patients is one
      of the cerebral artery's homeostatic responses to underfilling of the splanchnic
      arterial circulation.

PMID- 11322198
TI  - Intracellular pH regulation and Na+/H+ exchange activity in human hepatic
      stellate cells: effect of platelet-derived growth factor, insulin-like growth
      factor 1 and insulin.
AB  - BACKGROUND/AIMS: The Na+/H+ exchanger is involved in rat hepatic stellate cell
      (HSC) proliferation induced by platelet-derived growth factor (PDGF). We
      therefore evaluated in human HSC: (1) the mechanisms of intracellular pH
      regulation; (2) the relationship between Na+/H+ exchange activation and cell
      proliferation induced by PDGF, insulin-like growth factor 1 (IGF-1) and insulin.
      METHODS/RESULTS: pH(i) regulation was mainly dependent on the activity of the
      Na+/H+ exchanger, which was evaluated by measuring pH(i) recovery from an acute
      acid load. PDGF (25 ng/ml) gradually increased the activity of the Na+/H+
      exchanger which peaked at 18 h and remained stable until the 24th h. IGF-1 (10
      nmol/l), but not insulin (100 nmol/l), slightly but significantly increased the
      activity of the Na+/H+ exchanger. Amiloride (100 micromol/l) and 20 micromol/l 5
      N-ethyl-N-isopropyl-amiloride completely inhibited HSC proliferation (evaluated
      by measurement of bromodeoxyuridine incorporation) induced by PDGF and IGF-1, but
      did not affect proliferation of HSC induced by insulin. Finally, IGF-1 did not
      modify the activity of the Na+/Ca2+ exchanger. CONCLUSIONS: The Na+/H+ exchanger
      is involved in HSC proliferation induced by PDGF and IGF-1, whereas the
      proliferative effect of insulin is mediated by intracellular pathways which are
      Na+/H+ exchange-independent.

PMID- 11322199
TI  - 5'-Methylthioadenosine administration prevents lipid peroxidation and
      fibrogenesis induced in rat liver by carbon-tetrachloride intoxication.
AB  - BACKGROUND: 5'-Methylthioadenosine (MTA), a product of S-adenosylmethionine (SAM)
      catabolism, could undergo oxidation by mono-oxygenases and auto-oxidation. MTA
      and SAM effects on oxidative liver injury were evaluated in CCl4-treated rats.
      METHODS: Male Wistar rats were killed 1-48 h after poisoning with a single
      intraperitoneal CCl4 dose (0.15 ml/100 g) or with the same dose twice a week for
      14 weeks. Daily doses of MTA or SAM (384 micromol/kg), started 1 week before
      acute CCl4 administration or with chronic treatment, were continued up to the
      time of sacrifice. RESULTS: Acute and chronic CCl4 intoxication decreased MTA
      and, to a lesser extent, SAM and reduced glutathione (GSH) liver levels. MTA
      administration increased liver MTA without affecting SAM and GSH. SAM treatment
      caused complete/partial recovery of these compounds. MTA and, to a lesser extent,
      SAM prevented an increase in liver phospholipid hydroperoxides in acutely and
      chronically intoxicated rats and in prolyl hydroxylase activity and trichrome
      positive areas in chronically treated rats. MTA prevented upregulation of Tgf
      beta1, Collagen-alpha1 (I) and Tgf-alpha genes in liver of chronically
      intoxicated rats, and TGF-beta1-induced transdifferentiation to myofibroblasts
      and growth stimulation by platelet-derived growth factor-b of stellate cells in
      vitro. CONCLUSIONS: MTA and SAM protect against oxidative liver injury through
      partially different mechanisms.

PMID- 11322200
TI  - S-adenosylmethionine protects post-ischemic mitochondrial injury in rat liver.
AB  - BACKGROUND/AIMS: S-adenosylmethionine (SAM) is a thiol-containing compound with
      known therapeutic affects on cholestasis and hepatotoxicity. The aim of this
      study was to investigate the effect of SAM on the prevention of mitochondrial
      injury induced by hepatic ischemia and reperfusion. METHODS/RESULTS: Rats were
      subjected to 60 min of hepatic ischemia and 1 and 5 h of reperfusion. 2 h prior
      to ischemia, the animals received either vehicle or SAM intraperitoneally. In the
      vehicle-treated ischemic animals, serum aspartate aminotransferase levels
      increased at 1 h and again at 5 h of reperfusion and were reduced by SAM pre
      treatment. Similarly, mitochondrial lipid peroxidation was elevated in the
      vehicle-treated group, but this elevation was attenuated by SAM. In contrast,
      mitochondrial glutamate dehydrogenase activity and reduced glutathione
      concentration both decreased in the vehicle-treated group, and this decrease was
      also inhibited by SAM. Hepatic ATP levels in the vehicle-treated rats were found
      to be 42% lower 5 h after reperfusion, however, treatment with SAM elevated these
      ATP levels. SAM treatment increased the concentration of adenosine but inhibited
      the accumulation of hypoxanthine in the ischemic liver. CONCLUSION: SAM protects
      against mitochondrial injury, which prevents mitochondrial oxidant stress and
      improves ischemia-induced hepatic energy metabolism.

PMID- 11322201
TI  - Bilirubin-induced apoptosis in cultured rat neural cells is aggravated by
      chenodeoxycholic acid but prevented by ursodeoxycholic acid.
AB  - BACKGROUND/AIMS: Unconjugated bilirubin (UCB) can be neurotoxic in jaundiced
      neonates and in patients with Crigler-Najjar syndrome. UCB toxicity may culminate
      in cell death, however, the occurrence of apoptosis has never been investigated.
      Ursodeoxycholic acid (UDCA) is a strong modulator of the apoptotic threshold in
      both hepatic and nonhepatic cells. The aims of this study were to determine
      whether apoptosis plays a role in neural cell death induced by UCB, and to
      investigate the ability of UDCA to prevent cell death. METHODS: Cultured rat
      astrocytes were incubated with UCB (17 and 86 microM) plus albumin (5.7 and 28.7
      microM) for 4-22 h. In addition, astrocytes and neurones were treated with either
      UCB, 50 microM UDCA, or their combination for 4 h. Cultures were scored for
      nonviable cells by trypan blue dye exclusion. Apoptosis was assessed by Hoechst
      staining and terminal deoxynucleotidyl transferase-mediated deoxyuridine
      triphosphate nick end-labelling assay. RESULTS: UCB induced a concentration- and
      time-dependent decrease in astrocyte viability. Apoptosis was 4- and 7-fold
      increased after 4 h exposure to 17 and 86 microM UCB, respectively (P < 0.01).
      UDCA reduced apoptosis to <7%, which represents a appoximately 60% protection (P
      < 0.01). Cholic acid was not protective, and chenodeoxyholic acid aggravated UCB
      toxicity (P < 0.05). Finally, neurones showed a 1.5-fold greater sensitivity than
      astrocytes to UCB, while UDCA was still protective. CONCLUSIONS: UCB is toxic to
      both astrocytes and neurones, causing cell death through an apoptotic process.
      Moreover, UDCA inhibits UCB-induced apoptosis in neural cells and this could not
      be mimicked by other bile acids.

PMID- 11322202
TI  - Effect of the hepatitis B virus HBx protein on integrin-mediated adhesion to and
      migration on extracellular matrix.
AB  - BACKGROUND/AIMS: The hepatitis B virus HBx protein is associated with the
      development of hepatocellular carcinoma (HCC). However, its possible contribution
      to tumor spreading has not been explored. The migration of tumor cells through
      the extracellular matrix (ECM) represents a crucial step in tumor metastasis. Our
      aim was to study the effect of HBx on the integrin-mediated cell-ECM interaction,
      and its possible consequences for cell migration. METHODS: Cell-ECM interaction
      was evaluated by static adhesion experiments, using blocking and stimulating anti
      beta1 integrin mAbs. ECM receptor expression was analyzed by flow cytometry. The
      cellular distribution of the activated beta1 integrin subunit was determined by
      immunofluorescence analysis, and cell motility was determined by wound-healing
      assays. RESULTS: HBx-bearing cells showed decreased adhesion to fibronectin,
      which correlated with a decreased expression of the alpha5 integrin subunit. The
      activated beta1 subunit was redistributed to the tips of pseudopodial protrusions
      of HBx-bearing cells, whereas it was evenly localized in the control cells. HBx
      induced cell migration was abrogated by irreversible stimulation of beta1
      integrins. CONCLUSIONS: These results suggest that HBx might play a role in tumor
      spreading by modulating the adhesion-deadhesion balance of the cells in the
      primary tumor site and favoring integrin-mediated cell migration.

PMID- 11322203
TI  - Inactivation of SSI-1, a JAK/STAT inhibitor, in human hepatocellular carcinomas,
      as revealed by two-dimensional electrophoresis.
AB  - BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is one of the most common human
      cancers, and many efforts have been paid to discover aberrant expression control
      in HCC, however the specific molecular mechanisms involved in
      hepatocarcinogenesis remain to be determined. METHODS: To investigate genomic
      changes that occur in human primary hepatocellular carcinomas (HCC), we carried
      out restriction landmark genomic scanning. This two-dimensional electrophoretic
      system displays 2000-3000 NotI-landmark sites in a single gel. RESULTS: We
      detected one landmark spot that showed diminished signal intensities in a
      majority of the HCCs we examined. Cloning revealed that this spot represented a
      NotI-cluster sequence that was enriched with CpG dinucleotides in the promoter
      region of a gene encoding Janus kinase (JAK)-binding protein, SSI-1 (also known
      as JAB1 or SOCS-1). Expression of the SSI-1 gene was markedly reduced in half of
      eight HCCs analyzed. CONCLUSIONS: This protein regulates the Janus kinase signal
      transducers and activators of transcription signal transduction pathway, which
      transmits signals from cytokines to the intracellular apparatus. These data
      suggest that dysregulation of the pathway relate with progression of HCC.

PMID- 11322204
TI  - Serum response of hepatocyte growth factor, insulin-like growth factor-I,
      interleukin-6, and acute phase proteins in patients with colorectal liver
      metastases treated with partial hepatectomy or cryosurgery.
AB  - BACKGROUND/AIMS: The aim of the study was to compare the serum response of
      regeneration factors and acute phase proteins in patients treated with partial
      hepatectomy or cryosurgery. METHODS: The responses of serum hepatocyte growth
      factor (HGF), insulin-like growth factor-I (IGF-I) (free and total), interleukin
      6 (IL-6) and the acute phase proteins, C-reactive protein (CRP) and serum amyloid
      A (SAA) were examined in patients with colorectal liver metastases treated with
      partial hepatectomy (n = 14) or cryosurgery (n = 10). RESULTS: In both groups, IL
      6 peak levels at the end of the operation were followed by peak levels at day 1
      for HGF and CRP. SAA peak levels occurred on day 1 (hepatectomy group) and on day
      4 (cryo group). The total HGF, IGF-I, and IL-6 responses were comparable in both
      groups. CRP and SAA responses were higher in the patients treated with
      cryosurgery than in patients after hepatectomy. Free IGF-I trough levels were
      lower in partial hepatectomy patients than in cryosurgery patients. CONCLUSIONS:
      In patients with colorectal liver metastases the responses of the regenerating
      factors HGF, IGF-I, and IL-6 are comparable to those in patients treated with
      partial hepatectomy. Upregulation of acute phase protein production is higher in
      patients after cryosurgery than in patients after partial hepatectomy.

PMID- 11322205
TI  - Hepatitis C virus induced hypobetalipoproteinemia: a possible mechanism for
      steatosis in chronic hepatitis C.
AB  - BACKGROUND/AIMS: Steatosis could be the result of HCV (hepatitis C virus)-induced
      hypobetalipoproteinemia in patients with chronic hepatitis C. The aim of this
      study was to assess serum levels of main constituents of betalipoproteins and
      their relationship with steatosis in patients with chronic hepatitis C without
      known risk factors for steatosis. PATIENTS: One-hundred male patients with
      untreated biopsy proven non-cirrhotic chronic hepatitis C were included. Twenty
      nine of these patients were further treated with interferon. RESULTS: Cholesterol
      concentration was significantly lower in patients compared to three control
      groups: reference male population, patients with chronic hepatitis B or with non
      alcoholic fatty liver. In multivariate analysis, low apolipoprotein B
      concentration was an independent factor related with the degree of steatosis.
      Hypobetalipoproteinemia and degree of steatosis were significantly associated
      with infection with genotype 3. Among treated patients, only sustained
      virological responders had a significant increase of cholesterol (5.6 +/- 1 vs.
      4.7 +/- 1.3 mmol/l; P = 0.03) and apolipoprotein B concentrations (113 +/- 19 vs.
      75 +/- 14 mg/dl; P = 0.05). CONCLUSION: In chronic hepatitis C,
      hypobetalipoproteinemia is prevalent and associated with steatosis, especially in
      patients infected with genotype 3. The correction of hypobetalipoproteinemia
      following HCV eradication suggests that HCV itself could induce
      hypobetalipoproteinemia and steatosis.

PMID- 11322206
TI  - Hepatitis C viral kinetics in difficult to treat patients receiving high dose
      interferon and ribavirin.
AB  - BACKGROUND/AIMS: Hepatitis C viral (HCV) kinetic studies have demonstrated the
      increased antiviral effect of higher than standard dosages of interferon and of
      daily treatment schedules. Since interferon has a short half-life, twice-daily
      administration of interferon may be even more effective. METHODS: We evaluated
      the HCV kinetics in daily vs. twice-daily high dose interferon (IFN) therapy in
      combination with ribavirin in 24 difficult to treat patients. Patients were
      randomised to 10 MU IFN daily or 5 MU twice-daily for 4 weeks. RESULTS:
      Interferon efficacy (epsilon) was similar and very high for both groups (range
      99.83-99.97%). Clearance of infected cells (beta phase) tended to be slightly
      faster for patients on 5 MU bd (T1/2 70 vs. 90 h, ns). Clearance of infected
      cells was strongly related to initial viral load (T1/2 103 vs. 53 h, P = 0.002,
      for above versus below 2 x 10(6) copies/ml). In this study an additional phase
      with a temporary rise in viral load was observed between the alpha and the beta
      phase. CONCLUSION: Daily high induction dose is associated with nearly complete
      inhibition of viral replication even in difficult to treat patients. A twice
      daily schedule did not lead to further improvement. Clearance rate of infected
      cells was significantly correlated with initial viral load.

PMID- 11322207
TI  - Efficacy of 5 MU of interferon in combination with ribavirin for naive patients
      with chronic hepatitis C virus: a randomized controlled trial.
AB  - BACKGROUND: In chronic hepatitis C the schedule of interferon (IFN), 3 MU thrice
      weekly (tiw) plus ribavirin (1000-1200 mg/daily) needs further evaluation, as IFN
      dosages >3 MU achieve better responses. AIMS: To compare the efficacy of 5 MU tiw
      of IFN with (96 patients) or without ribavirin (96 patients) for 12 months in
      naive patients, to evaluate the effect of baseline features on the response to
      therapy, and to determine a reliable point in time during treatment to predict
      non-response. RESULTS: Sustained virologic response was 20.8% (95% CI 13-29) with
      IFN monotherapy and 54.2% (95% CI 44-64) with combination (P = 0.0001), the
      relapse rate 39.4% (95% CI 23-56) and 9% (95% CI 1-16) (P = 0.0007), and the
      combined rate of sustained biochemical and virologic response 22.7% (95% CI 14
      31) and 60.5% (95% CI 50-71) (P = 0.0001), respectively. Patients given
      combination therapy were more likely to respond regardless of baseline features.
      Apart from genotype non-1, predictive factors for IFN monotherapy were
      ineffective in predicting response to combination therapy. Using logistic
      regression analysis, IFN-ribavirin was the strongest predictor of response (X2 =
      21.3; P = 0.0001). Viral persistence at month 3 of therapy was a more accurate
      predictor than aminotransferase values for non-response to IFN monotherapy but
      not to combination therapy (positive predictive values of 98 and 82%,
      respectively). CONCLUSION: In this study, 5 MU of IFN combined with a standard
      dose of ribavirin has yielded the highest rate of sustained response reported to
      date. Further dose finding studies are warranted.

PMID- 11322208
TI  - High incidence of hepatitis B infections among chronic hepatitis cases of unknown
      aetiology.
AB  - BACKGROUND/AIMS: In approximately 5% of chronic liver disease cases, no aetiology
      can be identified. We selected sera from 50 patients with chronic hepatitis of
      unknown aetiology who were enrolled in this follow-up study whose aim is to gain
      insight into the possible role of viruses and to define potential clinical
      outcomes. METHODS: Patients' sera were screened with highly sensitive polymerase
      chain reaction assays for hepatitis B (HBV), C, D, and G viruses and TT virus.
      Sera were also retested for antibodies against the core antigen of HBV. RESULTS:
      Surprisingly, HBV DNA was detected in both serum and liver in 15/50 (30%)
      patients. Immunostaining for HBV antigens on biopsies from patients positive for
      HBV DNA showed HBcAg and/or HBsAg expression at low levels in 9/15 samples.
      Eleven of the fifteen patients were anti-HBc positive. With one exception, all
      patients carried HBV genomes at low levels (10(4) copies/ml or less).
      Histological signs of chronic liver disease were observed in all patients.
      CONCLUSION: Unrecognised HBV infections may account for a high proportion of
      chronic hepatitis cases of unknown aetiology. Improved HBV detection tests, which
      appear mandatory for the diagnosis and management of non-A non-E hepatitis as
      well as for improved safety of transfusions and transplantations are needed.

PMID- 11322209
TI  - Three-dimensional observations of the human hepatic artery (Arterial system in
      the liver).
AB  - BACKGROUND/AIMS: We examined the three-dimensional structures of the hepatic
      artery. MATERIALS/METHODS: A 39-year-old man who died of brain hemorrhage was
      autopsied. The liver was perfused with physiological saline and 20% formalin from
      the hepatic artery and portal vein. More than 700 serial sections were obtained
      from a paraffin-embedded block, and vascular reconstruction was performed under a
      light microscope. RESULTS: The hepatic artery divides into the axial artery and
      the peribiliary branch given off from it. These two systems also connect to each
      other by a few anastomoses. The former systematically supplies arterial blood to
      all the parenchymal liver cells. The latter forms two layers of plexes around the
      bile duct. The inner capillary layer is afferent and the outer vascular layer is
      efferent to the bile duct. CONCLUSION: To maintain constant sinusoidal blood
      flow, the terminal portions of the axial arteries may contract and thereby divert
      blood to peribiliary branches through bifurcations and anastomoses. The blood
      flow of the peribiliary capillary plexus may affect bile flow. The hepatic artery
      may act as a functional mediator between portal flow and bile excretion.

PMID- 11322210
TI  - New concepts in bilirubin neurotoxicity and the need for studies at clinically
      relevant bilirubin concentrations.

PMID- 11322211
TI  - Occult hepatitis B virus infection and liver disease: fact or fiction?

PMID- 11322212
TI  - Vascularity of liver tumours and recent advances in doppler ultrasound.

PMID- 11322213
TI  - Intrathoracic ascites.

PMID- 11322214
TI  - The HFE gene S65C polymorphism is rare among Bulgarian porphyria cutanea tarda
      patients.

PMID- 11322215
TI  - Increased plasma nitrate and nitrite concentrations in patients with hepatitis C
      virus infection.

PMID- 11322216
TI  - Efficacy and safety of lactosaminated human serum albumin-adenine arabinoside
      monophosphate in chronic hepatitis B patients non-responders to interferon
      therapy: a randomised clinical trial.

PMID- 11322217
TI  - Transjuglar liver biopsy: a review.
AB  - Transjugular liver biopsy is advocated as the technique of choice for use in
      those with contraindications to standard transabdominal biopsy. This technique
      was introduced to our unit in 1995. We audited our experience in performing
      transjugular liver biopsies over a three year period. Eighty-eight biopsies were
      performed in seventy-eight patients. We identified no major procedure related
      complications, despite the presence of coagulopathy and thrombocytopenia in 85%
      and 47% of cases respectively. Biopsy provided histological diagnosis in 97.7% of
      cases. Availability of the technique allowed us to perform liver biopsy safely
      and quickly in patients with both acute and chronic liver problems in whom
      standard techniques were contraindicated. We conclude that transjugular liver
      biopsy is a safe and effective technique, invaluable in the investigation and
      management of patients in a liver diseases referral unit.

PMID- 11322218
TI  - Audit of the impact of a major pop concert on the workload of two regional
      hospitals.

PMID- 11322219
TI  - The HELLP syndrome: maternal and perinatal outcome.
AB  - The HELLP syndrome is a rare condition with a variable presentation, and in
      general, the outlook for mother and baby is felt to be poor. The aims of this
      study were to determine the maternal and perinatal outcome in cases of the HELLP
      syndrome at the Rotunda hospital over a five-year period. A retrospective review
      of all cases of confirmed HELLP syndrome from 1/1/95 to 1/9/99 was undertaken.
      Antenatal, intrapartum and neonatal data and in particular, maternal and neonatal
      complications were recorded. There were 20 cases of HELLP syndrome over the 5
      year period. Mean maternal age was 29.8 (19-43) years. 70% were nulliparous. 80%
      delivered within 24 hours of diagnosis. 85% were delivered by caesarean section.
      Mean gestation at delivery was 33.5 (24-41) weeks, 65% of which were preterm. 70%
      of the babies were admitted to the neonatal intensive care unit (NICU). Mean
      birth weight was 1923g (440-4640g). Mean length of stay was 23.8 (1-68) days. 40%
      developed respiratory distress syndrome (RDS) with a mean duration of ventilation
      for these infants of 2.4 (0.5-7) days. There were 2 perinatal deaths both of whom
      weighed <500g. 95% of women were admitted to the High Dependency Unit. There were
      no maternal deaths. The mean interval to resolution of laboratory indices to
      within normal reference ranges was 11 (2-30) days. Maternal morbidity was high,
      but short-term, with full resolution in all cases. Once the diagnosis was made,
      delivery was immediate. The neonatal morbidity was also high and was most closely
      related to the gestation at delivery.

PMID- 11322220
TI  - Lambert-Eaton myaesthenic syndrome: a possible association with Hodgkin's
      lymphoma.
AB  - Lambert-Eaton myasthenic syndrome is a presynaptic neuromuscular junction
      disorder typically associated with small cell lung carcinoma. The characterstic
      electrophysiological abnormality is a low amplitude compound muscle action
      potential that shows a marked increment after maximal voluntary contraction or
      brief tetanic nerve stimulation. We describe a patient who had LEMS in
      association with Hodgkin's disease. A 61 year old woman presented with proximal
      muscle weakness 6 years following successful treatment of Hodgkin's disease. Her
      symptoms responded well to treatment with diaminopyridine. 9 additional patients
      have been described with LEMS in association with lymphoproliferative diseases. A
      systemic malignancy is usually found within 2 years of LEMS diagnosis but may
      present later. LEMS should be considered in patients with Hodgkin's disease
      presenting with muscle weakness.

PMID- 11322221
TI  - A pin in the neck.
AB  - We report a unique case of a 40 year old female who presented with recurrent open
      safety pin aspiration. She had a long history of personality disorder and self
      inflicted injury. On two occasions the open pin was removed with the aid of rigid
      bronchoscopy. However on one occasion a tracheostomy was required for removal of
      the safety pin.

PMID- 11322222
TI  - Hypergraphia in a patient with multiple medical problems.

PMID- 11322223
TI  - A study of the prevalence of cervical smear testing within female patients of a
      North Cork practice, and their understanding of the nature of cervical screen
      testing.

PMID- 11322224
TI  - Life-threatening angioneurotic oedema and ACE-inhibitors.

PMID- 11322225
TI  - Screening for hepatitis C (HCV) in specialist centres and in primary care.

PMID- 11322226
TI  - Critical care admission of obstetric patients.

PMID- 11322228
TI  - Doolin Lecture 2000 'Pharmaceuticals in the new Millennium'.

PMID- 11322229
TI  - The evolution of hip replacement surgery.

PMID- 11322230
TI  - Giant cell arteritis.

PMID- 11322231
TI  - Terminal care in the home--the general practice perspective.
AB  - A postal survey of 200 General Practitioners in south Dublin was undertaken. The
      aim was to elicit information about the problems experienced by GPs when caring
      for terminally ill cancer patients at home, and about their perceived needs for
      both further training and support services. All respondents experienced problems
      at least occasionally with control of pain and other symptoms. 25% of GPs
      surveyed frequently experienced difficulty with access to hospice in-patient
      beds, and with inadequate home support services. Overall, satisfaction with
      specialist Palliative Care Services was high. The majority of GPs felt that they
      would benefit from further education in Palliative Medicine. They also nominated
      ways to help them improve care of terminally ill patients at home including
      further training in pain control and symptom relief, more general and specialist
      nursing support, and more specialist medical support in the community.

PMID- 11322232
TI  - Ultrasonographic characterization of ovarian events and fetal gestational
      parameters in two southern black rhinoceros (Diceros bicornis minor) and
      correlation to fecal progesterone.
AB  - A tremendous potential exists for the application of transrectal ultrasonography
      as a tool to enhance the captive management of endangered species. Reproductive
      study of two southern black rhinoceros (Diceros bicornis minor) females was
      performed daily to every other day for a approximately 60 day period to document
      ovarian changes, and three times weekly in early pregnancy to once monthly in
      late pregnancy in order to characterize changes in fetal parameters throughout
      gestation. All ovarian and fetal anatomical structures were measured in
      millimeters. The mean (+/- SD) length of the estrous cycle or interovulatory
      period was 26 +/- 1.4 days (n=2 cycles). Follicular growth rate of a dominant
      follicle was approximately 3 mm/day once the follicle reached 35 mm in diameter.
      Ovulation was observed to occur at a mean (+/- SD) follicular diameter of 49.5 +/
      2.6 mm (n=4) and within 48 to 72 h after observed estrus (n=2). Large ovarian
      structures [mean (+/- SD) diameter of 71.7 +/- 2.9 mm; n=3], considered analogous
      to equine anovulatory hemorrhagic follicles, were observed to form in the winter
      months and suggest seasonal periods of reduced fertility. Fecal progesterone
      assays confirmed ultrasonographic events. Although preliminary, the results of
      fetal sexing are presented and compared to the horse. Our data indicate that
      fetal eye or fetal foot diameter measurements can be used to accurately predict
      gestational age from about 2 months to term, providing useful information to
      managers of both captive and wild rhino populations. The ability to identify and
      quickly release animals in late term pregnancy in the wild and thereby reduce
      abortions and neonatal mortalities in holding bomas is one potential practical
      conservation benefit of the fetal age predictive models.

PMID- 11322233
TI  - SRY-negative XX sex reversal in a pony: a case report.
AB  - A three year old pony with sexually ambiguous external genitalia was found to
      have a normal female karyotype (64, XX) and bilateral inguinal testes. The PCR
      analysis of blood samples revealed the absence of the Y chromosome sequences SRY,
      eTSPY and ZFY. No Y chromosome sequences were identified in DNA extracted from
      the gonads. The mechanism whereby XX sex reversal occurs in the absence of SRY is
      unknown.

PMID- 11322234
TI  - Effect of diet quantity and urea supplementation on oocyte and embryo quality in
      sheep.
AB  - The objective was to investigate the effects of dietary energy and urea
      supplementation on oocyte and embryo quality in sheep using in vivo and in vitro
      experimental models. Sixty-three ewes were fed grass meal at 0.5 or 2.0 times
      maintenance energy requirements (MER). The diet was supplemented with feed grade
      urea (U) for half of the ewes on each energy treatment. Ewes were stimulated with
      1000 IU eCG and either slaughtered on the day of pessary withdrawal, for in vitro
      embryo production, or mated and slaughtered on Day 5 for embryo recovery. Urea
      decreased cleavage rate (48.3 vs 39.7%) and consequently blastocyst rate (41.6 vs
      36.8%) but the differences were not significant. Oocytes from animals on 2.0 MER
      had a lower cleavage rate (54.9 vs 36.0%) and blastocyst yield (49.3 vs 31.4%)
      than those on 0.5 MER. However, there was an interaction between urea and energy
      for cleavage (P = 0.04) and blastocyst yield (P = 0.03) indicating a variable
      response to urea in the presence of high energy. This was manifested by a
      decrease in cleavage rate in the presence of urea and high energy (22%, 8 of 36),
      and a reduction in blastocyst development (19%, 7 of 36). When blastocyst
      development rate was expressed as a proportion of cleaved oocytes there was no
      difference between groups; in addition, there was no difference between groups in
      terms of blastocyst hatching rate (overall mean 66.1%) or blastocyst cell number
      on Day 8 (overall mean +/- SEM, 138.4 +/- 9.0, n=61). The effect of urea on
      cleavage rate in vivo was more severe. Urea supplementation reduced (P<0.001) the
      cleavage rate (93 vs 62%). Despite this, the yield of blastocysts was unaffected.
      Oocytes from ewes on 0.5 MER exhibited a lower (P<0.05) cleavage rate than those
      on 2.0 MER (66 vs 87%). This effect was also apparent at the blastocyst stage
      (40.0 vs 50.9%), although the difference was no longer significant. There were no
      differences in hatching rate (overall mean 70.7%) or blastocyst cell numbers
      (overall mean +/- SEM, 166.3 +/- 15.6, n=40). Collectively, these results suggest
      that both high dietary energy and urea content influence subsequent embryo
      development in vitro, and the deleterious effects of urea are likely influenced
      by concomitant energy intake.

PMID- 11322235
TI  - Sexing and multiple genotype analysis from a single cell of bovine embryo.
AB  - We described a procedure for multiple genotype analysis (determination of sex and
      of three genetic markers) from a single cell derived from bovine preimplantation
      embryo. It consists of primer extension preamplification-polymerase chain
      reaction (PEP-PCR) and subsequent single assay or multiplex PCR. A single
      blastomere that was isolated by microaspiration from bovine embryos at the 16- to
      32-cell stage then was lysed and was subjected to the PEP-PCR. When testing 75
      embryos, efficiency of genotyping by standard PCR for kappa-casein, growth
      hormone (GH) and prolactin (PRL) polymorphic alleles was 91, 88 and 89%,
      respectively. Sexing efficiency in the multiplex PCR was 91%, based on the
      amplification of Y-specific locus using kappa-casein internal standard. The
      microaspiration of a single blastomere was shown not to be invasive for the
      embryos. It did not alter their development potential in vitro (P > 0.05), as was
      seen by obtaining a similar percentage of embryos developing further into the
      blastocyst stage in the group subjected to biopsy (44/75, 59%) and in the control
      group of embryos (30/50, 60%).

PMID- 11322236
TI  - Effects of estradiol-17beta administration on steady-state messenger ribonucleic
      acid (MRNA) encoding equine alpha and LH/CGbeta subunits in pituitaries of
      ovariectomized pony mares.
AB  - The process of sexual recrudescence in the springtime in mares is characterized
      by renewal of follicular growth and acquisition of steroidogenic competence.
      Concomitant with renewal of follicular steroidogenesis is re-establishment of LH
      biosynthesis and secretion. Research results from our laboratory indicate that
      increased estradiol and LH secretion occur in close temporal association before
      the first ovulation of the year. Therefore, the hypothesis tested in this
      experiment was that estrogen administration to ovariectomized pony mares during
      the equivalent time of early vernal transition would enhance LH biosynthesis as
      monitored by messenger ribonucleic acid (mRNA) encoding for the pituitary
      subunits of LH (alpha and LH/CGbeta). Mares were administered either sesame oil
      vehicle control, or estradiol (5 mg i.m. twice daily in sesame oil) for 3, 6 or 9
      days, beginning on February 2. The pituitary glands were harvested, and examined
      for LH subunit mRNA by Northern Blot and slot blot analysis. There was a
      significant increase in LH secretion after 6 days of estradiol secretion compared
      with control vehicle administration. Similarly, there was a significant increase
      in both alpha and LH/CGbeta subunit mRNA when estradiol was administered for 9
      days. These data indicate that estrogen stimulates LH subunit formation in mares
      during early equivalent vernal transition. These data do not, however,
      discriminate between a direct pituitary effect of estrogen, and a hypothalamic
      effect. Whether the surge of estradiol just prior to the first ovulation of the
      year is essential for the renewed biosynthesis of LH subunits cannot be
      determined from these data. However an important role of estrogen in the final
      stages of sexual recrudescence is indicated.

PMID- 11322237
TI  - Effects of ovarian input on GnRH and LH secretion immediately postovulation in
      pony mares.
AB  - The potential involvement of ovarian factors in regulating GnRH and LH
      postovulation was studied in ovarian intact (Group 1; n=3) and ovariectomized
      (OVX; Group 2; n=3) mares (OVX within 12 hr of ovulation). Blood samples were
      collected every 10 min for 6 hr from jugular vein (JV) and intercavernous sinus
      (ICS) during estrus and on Day 8 postovulation for LH and GnRH analysis.
      Additionally, JV samples were collected twice daily (12-hr intervals) for 30 days
      for LH and progesterone (P4) analysis. A significant treatment x day effect
      (P<0.0001) describes declining plasma LH concentrations in intact mares, and
      regression analysis indicated that response curves were not parallel (P<0.001).
      Plasma LH concentrations remained elevated in OVX mares. LH increased further in
      OVX mares by Day 8 post-OVX (P<0.06), reflecting the increased (P<0.07) LH
      episode amplitude. GnRH decreased from estrus to Day 8 in both groups reflecting
      an effect of sampling period (P<0.03). GnRH episode amplitude declined (P<0.08)
      from estrus (62.8+/-3.1 pg/mL) to Day 8 (46.3+/-3.1 pg/mL) in OVX mares, but not
      in control mares (intact estrus, 36.5+/-6.4; intact Day 8, 37.5+/-7.3; OVX
      estrus, 62.8+/-3.1; OVX Day 8, 46.3+/-3.1 pg/mL). In conclusion, we propose that
      postovulatory LH decline requires ovarian feedback in mares, and that OVX alters
      GnRH secretory dynamics such that LH concentrations does not decline
      postovulation and, in fact, is further elevated with time after OVX.

PMID- 11322238
TI  - Ultrastructural and cytochemical comparison between calf and cow oocytes.
AB  - The use of prepubertal females (calves) to obtain oocytes for in vitro
      fertilization (IVF) programs, is being analyzed currently. This will increase the
      availability of female oocytes and will allow a reduction of the interval between
      generations. Differentials in the development capability of calf and cow oocytes
      have been assessed by different authors, establishing several ultrastructural and
      metabolic differences between them. This paper analyzes the morphometric and
      cytochemical differences between calf and cow oocytes through microscopic
      techniques. The oocytes morphologically classified as good are processed for
      electron microscopy a) in Epon 812 epoxy resin for morphometric analysis or b) in
      low temperature Lowycril K4M resin for cytochemical evaluation using Con A, GS,
      LPA, UEA, and WGA lectins marked with colloidal gold as probes. Calf oocytes show
      a greater density of microvilli on their surface and a greater number of
      endocytosic vesicles than those of the cow. On the other hand, cow oocytes show a
      larger superior mitochondrial population. In the cumulus cells it can be seen
      that calf oocytes have a greater volume of lipid droplets. Cytochemical analysis
      shows that calf oocytes have lectin marking restricted to the plasmic membrane,
      highlighting the presence of LPA. In cow oocytes, lectin marking can be seen both
      on the plasmic membrane and in the vacuoles, in both cases, with the LPA
      highlighted. In the zona pellucida of calf and cow oocytes, the same sugars
      appear (GS, LPA, WGA), and marking with LPA is more extensive in cow oocytes.

PMID- 11322239
TI  - Effect of the in vitro culture system on the kinetics of blastocyst development
      and sex ratio of bovine embryos.
AB  - Bovine blastocysts were produced using 6 different systems: 5 commonly used in
      vitro culture systems (synthetic oviduct fluid medium - SOF- without fetal calf
      serum, SOF supplemented with 10% serum for the entire culture period, SOF
      supplemented with 10% serum from Day 4 of culture, M199 coculture with bovine
      oviduct epithelial cells, M199 coculture with granulosa cell monolayer) and 1 in
      vivo culture system involving collection of blastocysts from superovulated bovine
      donors at Day 7. Zygotes obtained from IVM/IVF were assigned randomly to 1 of the
      5 systems tested and were cultured for 9 d (Day 0= day of insemination).
      Cleavage, development to the blastocyst stage and blastocyst sex ratio were
      assessed in all treatments. In addition, the effect of the IVC system on the
      kinetics of blastocyst development and sex ratio was assessed on Days 6, 7, 8,
      and 9. The presence of fetal calf serum in SOF not only resulted in faster
      development (19.1% of blastocysts in SOF supplemented with serum vs 7.1% in
      absence of serum at Day 6; P < 0.05) and increased blastocyst production (47.5%
      of blastocysts in SOF supplemented with serum vs 34.4% in absence of serum; P <
      0.05) but it also enhanced overall male survival. The coculture systems produced
      fewer blastocysts than culture in SOF (27.6 to 28.3% in coculture vs 47.5% in SOF
      supplemented with serum; P < 0.05), but similar to SOF without fetal calf serum,
      they had no effect on blastocyst sex ratio.

PMID- 11322240
TI  - Plasma and pituitary concentrations of gonadotropins (FSH and LH) in minke whales
      (Balaenoptera acutorostrata) during the feeding season.
AB  - This study investigated plasma and pituitary concentrations of follicle
      stimulating hormone (FSH) and luteinizing hormone (LH) and steroid hormones
      (progesterone: P4, testosterone:T, estradiol-17beta: E2) by enzyme-immunoassay
      (EIA) in minke whales (Balaenoptera acutorostrata) captured during the feeding
      season (December to March) in the Antarctic Ocean. Plasma FSH and LH levels in
      female minke whales were higher (P <0.05) than in male whales. Although the
      pituitary weight was not significantly different between male and female whales,
      pituitary FSH and LH levels were higher in females than in males (P<0.01) and
      mature whales than immature whales (P<0.05). Plasma levels of FSH, T and E2 were
      not significantly different between immature and mature male whales, but plasma
      LH and pituitary FSH and LH levels were higher (P<0.05) in mature than in
      immature whales. In both immature and mature whales regardless of gender,
      pituitary FSH and LH levels were correlated significantly (r=0.69: P<0.01). In
      mature male whales, plasma T and E2 levels (r=0.60: P<0.01), and testis weight
      and plasma T levels (r=0.46: P <0.05) were correlated. In immature female whales,
      plasma FSH and LH levels were highly correlated (r=0.68: P<0.001), but were not
      for mature female whales. The results show that gender and maturity influence
      gonadal and pituitary function of minke whales during the feeding season.

PMID- 11322241
TI  - Validation of the sperm quality analyzer (SQA) for dog sperm analysis.
AB  - In the present study, a simple and inexpensive unit (the Sperm Quality Analyzer
      SQA), was evaluated for dog sperm analysis. Our objective was to propose a cheap,
      accurate and convenient device to be used in veterinary practices involved with
      dog fertility assessment and artificial insemination. The device was tested by
      analyzing repeatability and accuracy at different sperm concentrations and
      motility characteristics. The Sperm Motility Index (SMI), a numeric index
      provided by the SQA, was compared with the results obtained using a computer
      aided sperm analyzer (Hamilton Thorn IVOS 10). The correlation between SMI and
      some sperm parameters as well as predictive values of the SMI were established.
      The dog sperm data provided by the SQA were consistent and repeatable
      (coefficient of variability below 10% for all concentrations tested). The SMI was
      significantly dependant on motile sperm concentration and a positive significant
      correlation was established for the different motile sperm concentrations from a
      concentration of 25 x 10(6) up to over 200 x 10(6) cells/mL. Zero motility did
      not affect SMI because non-motile cells, regardless of their concentration, do
      not cause any fluctuations in the optical density (OD). Over the tested 200 x
      10(6) cells/mL value, a correlation still could be observed but it was not
      statistically significant, possibly because of a saturation of the system. In dog
      semen, the correlation is better between SMI values and the number of motile
      spermatozoa than with the overall motile concentration. Based on this
      observation, a predictive value was given to the SMI allowing for a sorting of
      dog ejaculates in 3 sperm categories (SMI <100, 100<SMI<250, SMI>250) each
      characterized by a range of sperm number and motility. If a positive correlation
      between the SMI categories and fertility has been demonstrated in humans, such a
      correlation needs to be established in dogs.

PMID- 11322242
TI  - Post-thaw survival of ram spermatozoa and fertility after insemination as
      affected by prefreezing sperm concentration and extender composition.
AB  - A study was conducted to investigate the effects of prefreezing sperm
      concentration using two extenders on post-thaw survival and acrosomal status of
      ram spermatozoa (Experiment 1) and fertility after intrauterine insemination with
      differing doses of semen (Experiment 2). In autumn (Northern hemisphere), semen
      was collected by artificial vagina from 8 adult Leccese rams and ejaculates of
      good quality semen were pooled. Two extender systems for cryopreservation were
      considered, one based on milk-lactose egg yolk (Milk-LY) and the other based on
      tris-fructose egg yolk (Tris-FY). Experiment 1 (2 x 6 factorial scheme) examined
      the in vitro characteristics of spermatozoa in relation to the Milk-LY and Tris
      FY extenders and six prefreezing sperm concentrations (50, 100, 200, 400, 500 and
      800 x 10(6) spermatozoa/mL). Experiment 2 (2 x 4 factorial) evaluated the
      influence of the Milk-LY vs Tris-FY extenders and four doses (20, 40, 80 and 160
      x 10(6) spermatozoa/0.25 mL) corresponding to prefreezing spermatozoa
      concentrations of 100, 200, 400 and 800 x 10(6) spermatozoa/mL, on fertility of
      ewes inseminated in uterus by laparoscope. Prefreezing sperm concentration
      influenced (P < 0.01) freezability of spermatozoa and affected negatively all the
      in vitro parameters at 800 x 10(6) spermatozoa/mL. Overall, Milk-LY tended to
      ensure higher viability and acrosomal integrity of spermatozoa after thawing at
      the intermediate sperm densities (range 100 to 500 x 10(6) spermatozoa/mL). At
      500 x 10(6) spermatozoa/mL concentration corresponded the best condition for
      survival of spermatozoa (71.2%), acrosome integrity (71.5%) and acrosomal loss
      (6.0%). At the lowest sperm concentration (50 x 10(6) spermatozoa/mL), Tris-FY
      resulted in a higher survival rate than Milk-LY (61.3%, P < 0.05) and lower
      acrosomal loss (9.7%, P < 0.05). Milk-LY supported spermatozoa motility better
      than Tris-FY after incubation at sperm concentration between 50 and 400 x 10(6)
      spermatozoa/mL (0.05 > P < 0.01). Semen doses of 20 to 40 x 10(6) spermatozoa/ewe
      provided satisfactory fertility rates (64 to 81%). The increase of inseminate
      doses to 160 x 10(6) spermatozoa/ewe failed to improve fertility, actually
      tending to decrease lambing rates.

PMID- 11322243
TI  - Changes in plasma gonadotrophin and prolactin concentrations following castration
      of the pony stallion.
AB  - Concentrations of gonadotrophins and prolactin were recorded in pony stallions
      castrated during the early breeding season, to examine the regulatory role of the
      gonad at a time when testosterone has been postulated to exert positive feedback
      on LH secretion. Further, gonadotrophin concentrations in geldings are reported
      to return to values within the normal range of the entire stallion. In an attempt
      to characterize this species-specific reversal, the gonadotrophin concentrations
      of 6 male ponies castrated on 25 March were monitored for 4 months, and 4
      stallions were used to generate control data. Blood samples were collected daily,
      from 3 d before to 10 d after castration (Day 0), and weekly thereafter until Day
      122. The pituitary response to castration was immediate. Castration resulted in a
      previously unreported, dramatic (13-fold) but transient (3 d) surge in
      circulating concentrations of LH. Concentrations of LH and FSH increased in a
      logarithmically scaled (LH, R2 = 0.77; FSH, R2 = 0.93) manner over the subsequent
      5 wk, during which temporal changes in concentrations of both hormones were
      strongly correlated (R2 = 0.97). The ratio of plasma gonadotrophin concentrations
      was consistent throughout (LH:FSH, 1.43 +/- 0.04). Maximal concentrations of LH
      (20.58 +/- 1.97 ng/mL, Day 34.8 +/- 3.2) were attained approximately 2 wk before
      the peak in FSH (16.99 +/- 1.97 ng/mL, Day 49.7 +/- 3.0). Plasma gonadotrophin
      concentrations exceeded those of entire stallions throughout the study. The
      equine testes inhibited LH secretion during the early breeding season, and no
      chronic decrease in plasma gonadotrophin concentrations was recorded. However,
      the LH surge evident for 3 d immediately afer castration, may be related to the
      dynamic seasonal interaction between gonadal steroids and the regulation of
      pituitary gonadotrophin release.

PMID- 11322244
TI  - Short-term treatment with a controlled internal drug releasing (CIDR) device and
      FSH to induce fertile estrus and increase prolificacy in anestrous ewes.
AB  - The objectives were to evaluate, in anestrous ewes, the effectiveness of a CIDR-G
      device (0.3 g progesterone) administered for 5 d to induce estrus; and FSH
      (Folltropin; 55 mg NIH-FSH-P1 equivalent) in saline:propylene glycol (1:4) 24 h
      before insert removal (Day 0), to increase ovulation rate and prolificacy. Ewes
      of mixed breeding were assigned at random to 3 treatments: control (C; n = 125),
      5 d progesterone (P5; n = 257) and 5 d progesterone plus FSH (P5F; n = 271).
      Intact rams were joined at insert removal and ewes were observed every 24 h for 3
      d. On Day 14, the ovulation rates of all ewes detected in estrus in the treated
      groups were determined using transrectal ultrasonography. Rams were removed on
      Day 26 to 31. Ewes were examined for pregnancy then, and again 20 to 25 d later
      to detect ewes that conceived to the second service period. Percentage of ewes
      marked by rams was higher in progesterone-treated (77%) than in C (20%; P <
      0.01), but did not differ between P5 and P5F. The ovulation rate (1.95+/-0.04)
      did not differ due to FSH. Conception (68%) and pregnancy (52%) rates were higher
      in progesterone-treated (P < 0.01) than in C (0%) ewes. Estrous response varied
      quadratically with time after ram introduction, and the conception rate varied
      quadratically with the time of observation of onset of estrus. Over two service
      periods more progesterone-treated than C ewes lambed (65 vs 45%; P < 0.01). Lambs
      born per ewe exposed (0.7+/-0.1, 1.0+/-0.1, and 1.1+/-0.1 for C, P5 and P5F,
      respectively) was increased by progesterone (P < 0.05). Litter size to the first
      service period (1.59+/-0.04) and overall (1.54+/-0.03) did not differ among
      treatment groups. FSH-treated ewes tended to have more lambs (1.67+/-0.1) than
      did ewes receiving progesterone alone (1.5+/-0.1; P = 0.06) and than did ewes
      lambing to the second service period (1.5+/-0.1; P = 0.06). In summary, a 5-d
      progesterone pre-treatment of anestrous ewes induced estrous cycles and increased
      the pregnancy rates. A single injection of FSH only tended to increase litter
      size.

PMID- 11322245
TI  - Can HIV infection be cured?

PMID- 11322246
TI  - A randomized controlled trial of a protease inhibitor (saquinavir) in combination
      with zidovudine in previously untreated patients with advanced HIV infection.
AB  - This study assessed the activity and tolerability of an HIV-protease inhibitor,
      saquinavir, alone or in combination with zidovudine. A total of 92 previously
      untreated HIV-infected patients with CD4 cell counts < 300 cells/mm3 participated
      in a parallel, randomized double-blind study. Patients were randomized to receive
      one of five treatments, each three times a day: 600 mg of saquinavir; 200 mg of
      zidovudine; 75, 200 or 600 mg of saquinavir in combination with 200 mg of
      zidovudine. The primary treatment period was 16 weeks, with monthly extensions in
      patients who did not show major disease progression or toxicity. The main
      measures of the efficacy of therapy used were changes in CD4 cell counts and in
      the concentration of HIV-1 RNA in the plasma (as determined by quantitative
      polymerase chain reaction). The 600 mg dose of saquinavir in combination with
      zidovudine induced a 1.6 log (after 4 weeks) and a 0.7 log (after 16 weeks)
      median reduction in plasma RNA concentration; this reduction was greater than
      those seen in the other four treatment groups. The combination of 600 mg of
      saquinavir with zidovudine also resulted in a larger and more sustained
      improvement in the CD4 cell count than either saquinavir or zidovudine
      monotherapy or the other combination therapies. In the group receiving 200 mg of
      saquinavir in combination with zidovudine, the maximal median change in CD4 cell
      count occurred at week 2 (85 cells/mm3), and by week 16 had fallen to 15
      cells/mm3. In the group receiving 600 mg of saquinavir plus zidovudine, the
      median change in CD4 cell count remained high for the 16-week period (median
      change of 48 cells/mm3 at week 2 and 61 cells/mm3 at week 16). Saquinavir was
      safe and very well tolerated, either alone or in combination with zidovudine. The
      incidence of adverse events was greater in the four groups receiving zidovudine
      therapy, and all the most commonly reported adverse events have previously been
      associated with zidovudine therapy. Few changes in laboratory values occurred
      during the study, except for known zidovudine-associated toxicities. The most
      frequent abnormalities were raised aspartate aminotransferase and alanine
      aminotransferase levels, depressed calcium levels, and abnormally high or low
      phosphate levels. Despite the low oral bioavailability of saquinavir, combined
      virological and immunological data show definite antiviral activity in vivo for
      the combination of saquinavir at 600 mg plus zidovudine at 200 mg (each three
      times daily). The combination of drugs with different mechanisms of action
      represents an advance in the treatment of HIV infection.

PMID- 11322247
TI  - Antiviral activities of penciclovir and famciclovir on duck hepatitis B virus in
      vitro and in vivo.
AB  - Chronic hepatitis B virus (HBV) infection is a major health problem worldwide.
      Antiviral strategies available at present, including interferon-alpha, have only
      limited efficacy, leading us to analyse the antiviral effects of penciclovir and
      famciclovir in the duck hepatitis B virus (DHBV) model of HBV infection in vitro
      and in vivo. In DHBV-infected duck hepatocytes, penciclovir effectively inhibited
      viral replication, with a concentration giving half-maximal inhibition of 0.25
      microM. Furthermore, in vivo, penciclovir and its orally administered prodrug
      famciclovir strongly inhibited DHBV replication. These data demonstrate that
      penciclovir and famciclovir both have strong antiviral activities, and suggest
      that these agents might be useful for treating HBV infection in humans.

PMID- 11322248
TI  - Antiviral activity of a conjugate of adenine-9-beta-D-arabinofuranoside 5'
      monophosphate and a 9 kDa fragment of arabinogalactan.
AB  - An arabinogalactan conjugate containing a 9 kDa fragment of arabinogalactan and
      adenine-9-beta-D-arabinofuranoside 5'-monophosphate (araAMP), denoted AG(9 kDa)
      araAMP, has been synthesized and characterized. In 2.2.15 (human hepatoblastoma)
      cells, the attachment of araAMP to AG(9 kDa), a ligand of the asialoglycoprotein
      receptor, decreased the effective concentration for inhibiting extracellular
      hepatitis B virus (HBV) production by 90% (EC90) from 17 to 0.9 microM adenine
      arabinoside (araA) equivalents, and increased the cytotoxic concentration (CC50)
      from 188 to > 17 300 microM araA equivalents. Hence, the selectivity index
      (CC50/EC90) of araA was improved from 11 (188/17) to > 19200 (17 300/0.9) by
      conjugation with the 9 kDa fragment of arabinogalactan. AG(9 kDa)-araAMP did not
      affect the production of viral RNA or viral proteins. In the woodchuck hepatitis
      model, AG(9 kDa)-araAMP inhibited woodchuck hepatitis virus (WHV) DNA replication
      at a dose of 0.3 mg of araA equivalents per kg; in this case, AG(9 kDa)-araAMP
      was 20-30 times more potent than was unconjugated araA. AG(9 kDa)-araAMP was
      effective by intramuscular or subcutaneous administration. The reduction in HBV
      DNA levels obtained in 2.2.15 cells and of WHV DNA levels in woodchucks was
      sustained after treatment with AG(9 kDa)-araAMP ceased. In both cases, viral DNA
      gradually returned to pre-treatment levels.

PMID- 11322249
TI  - Heterogeneity of physician agreement with recommended therapeutic guidelines for
      the management of HIV-associated disease.
AB  - The aims of this study were to assess the degree of heterogeneity in the
      knowledge of therapeutic management of HIV infection among HIV-experienced
      physicians in British Columbia, Canada, and to identify associations between
      physician characteristics and their agreement with contemporary therapeutic
      guidelines. A self-administered anonymous questionnaire was mailed to 6500
      physician members of the British Columbia Medical Association. The questionnaire
      provided information about demographic and personal characteristics, including
      sex, age, medical specialization and practice location; level of experience in
      treating HIV-infected patients; use of HIV testing procedures; use of
      preventative vaccinations and tests; and preferred approaches to antiretroviral
      therapy and the prophylaxis and acute treatment of opportunistic infections. We
      compared physicians' patterns of knowledge with contemporary recommendations.
      Logistic regression identified associations between physician characteristics and
      their agreement with contemporary guidelines. A total of 463 HIV-experienced
      physicians (a high proportion of the HIV-experienced physicians in British
      Columbia, Canada) responded to the questionnaire. The agreement with contemporary
      guidelines about HIV testing and preventative vaccinations and tests among
      responders ranged from 27% to 71%. For antiretroviral therapy, agreement with the
      guidelines ranged from 12% to 35%. For the prophylaxis and treatment of
      opportunistic infections, agreement with the guidelines ranged from 11% to 89%
      (prophylaxis) and from 46% to 91% (treatment). Regression analysis revealed that
      physicians actively involved in the care of HIV-infected patients were more
      likely to agree with the guidelines in all areas of patient care. General
      practitioners were more likely to agree with the guidelines regarding
      preventative therapies, and male general practitioners under 45 years old were
      more likely to agree with the guidelines on antiretroviral therapy. Our data
      confirm that there is substantial heterogeneity in the management of HIV
      associated disease, including some deviations from contemporary guidelines.
      Concordance with contemporary guidelines increased with the physician's level of
      HIV-related experience. Our results support the idea that adherence to state-of
      the-art practices may be responsible, at least in part, for the recently
      described association between physician experience and improved survival of HIV
      infected individuals.

PMID- 11322250
TI  - Predictive value of codon 215 reverse transcriptase mutation on the efficacy of
      didanosine in HIV-infected, zidovudine-experienced patients.
AB  - We investigated whether or not mutations at codon 215 in the HIV reverse
      transcriptase-encoding gene predicted a lower efficacy of didanosine therapy, as
      defined by survival of patients and change in CD4 cell counts in 121 HIV
      infected, zidovudine-experienced patients. A trend for shorter survival, although
      not reaching significance, was observed for patients with HIV strains with the
      reverse transcriptase codon 215 mutation (P = 0.07), but this trend disappeared
      after adjustment for initial CD4 cell counts. During the first 3 months on
      didanosine therapy, the increase in CD4 cell counts was greater in patients who
      were wild type at codon 215 than in those with the mutation at codon 215 (P =
      0.03). These data suggest that there was a better initial CD4 response to
      didanosine therapy in patients with HIV without the mutation at codon 215, but
      that this response did not translate into increased survival.

PMID- 11322251
TI  - Foscarnet-induced changes in plasma concentrations of total and ionized calcium
      and magnesium in HIV-positive patients.
AB  - The time course and magnitude of foscarnet-induced changes in plasma
      concentrations of total and ionized calcium and magnesium were investigated in 13
      male HIV-positive patients who had no active cytomegalovirus-associated disease.
      The patients had a mean age of 36 years (range 25-49 years) and a mean CD4 cell
      count of 550 cells/mm3 (range 130-1280 cells/mm3). Peak (mean +/- SD) plasma
      concentrations of foscarnet (0.89+/-0.10 mmol/l) were seen at the end of the
      period of drug infusion (90 mg/kg of foscarnet was infused over 2 hours) and
      declined with a terminal half-life of 5.7+/-0.7 hours. Plasma concentrations of
      total calcium declined over an 8-hour period, with the lowest concentration
      occurring after 4 hours (baseline: 2.29+/-0.09 mmol/l; lowest: 2.18+/-0.07
      mmol/l; P < 0.001). By contrast, the lowest plasma concentration of ionized
      calcium occurred after 2 hours (baseline: 1.25+/-0.04 mmol/l; lowest: 0.99+/-0.05
      mmol/l; P < 0.001), before gradually recovering to baseline levels over the next
      10 hours. The mean maximal decrease in total calcium was 0.11+/-0.06 mmol/l,
      compared with 0.26+/-0.04 mmol/l for ionized calcium (P < 0.001). Plasma
      concentrations of total magnesium declined from 0.79+/-0.06 mmol/l (baseline) to
      0.74+/-0.04 mmol/l (P < 0.05) after 4 hours and remained at this level after 8
      hours. However, plasma concentrations of ionized magnesium fell steeply from
      0.56+/-0.03 mmol/l to 0.39+/-0.03 mmol/l at 2 hours (P < 0.001), followed by a
      gradual recovery over the next 10 hours. The mean maximal decrease in total
      magnesium was 0.05+/-0.08 mmol/l, compared with 0.18+/-0.03 mmol/l (P < 0.001)
      for ionized magnesium. In summary, we found that foscarnet-induced changes in the
      plasma concentrations of total calcium and magnesium were dissociated from the
      corresponding changes in ionized calcium and magnesium. The maximal decreases in
      the plasma concentrations of total calcium and magnesium were smaller in
      magnitude and occurred much later than did the changes in ionized calcium and
      magnesium. The relative changes in the plasma concentration of ionized magnesium
      were greater than those of ionized calcium, indicating that foscarnet binds
      preferentially to the magnesium ion.

PMID- 11322252
TI  - Safety and activity of zalcitabine and zidovudine combination in HIV-positive
      people with CD4 cell counts < or = 300 cells/mm3. The Roche M50002 Study Group.
AB  - We carried out an open-label, single-arm, multicentre 1-year study of the safety
      and activity of therapy with a zalcitabine-zidovudine combination in 561 patients
      with CD4 cell counts < or = 300 cells/mm3 who were either established on
      zidovudine or had not previously received antiretroviral therapy. Additionally,
      we assessed the impact of baseline characteristics on clinical outcome during
      therapy. The study used specialist HIV-care centres in Argentina, Belgium,
      Brazil, Hungary, Italy, Luxembourg, Mexico, Peru, Spain and Venezuela.
      Participants were regularly assessed for adverse experiences, changes in
      laboratory values and clinical progression. A total of 561 patients entered the
      study, with 353 completing 12 months of follow-up. The 492 zidovudine-experienced
      patients had a mean duration of previous therapy of 18.5 months. No unexpected
      adverse events were reported. Peripheral neuropathy was observed in 12.7% of
      patients and was more common in participants with CD4 cell counts < or = 100
      cells/mm3 at baseline. Clinical disease progression was significantly associated
      with lower baseline CD4 cell counts, a history of previous AIDS-defining events
      and a baseline haemoglobin < 11 g/dl. The median CD4 cell count at baseline was
      141.5 cells/mm3, rising to 174 cells/mm3 after 12 weeks and to 148 cells/mm3 at
      12 months. In conclusion, zalcitabine-zidovudine combination therapy was found to
      be well tolerated in this patient population, although patients with CD4 cell
      counts < or = 100 cells/mm3 were found to require more intensive monitoring for
      toxicities and disease events. The changes in the CD4 cell count seen in this
      study and in others provide evidence of the therapeutic activity of this
      combination.

PMID- 11322253
TI  - Short-term anti-HIV activity of the combination of didanosine and hydroxyurea.
AB  - The synergistic action of hydroxyurea with some other antiretroviral drugs led us
      to evaluate the effect of therapy with the combination of didanosine and
      hydroxyurea in HIV-1-infected patients. We aimed to assess the anti-HIV activity
      of therapy with this combination by measuring variations in viral load and in CD4
      cell counts. We also evaluated the potential side effects of this drug
      combination in HIV-1-positive patients with advanced disease. A total of 15 HIV-1
      seropositive homosexual men with a mean baseline CD4 cell count of 149 cells/mm3
      (range: 1-430 cells/mm3) were recruited to the study, and received didanosine
      (200 mg) plus hydroxyurea (500 mg) twice daily for 12 weeks. Ten patients were
      didanosine naive and five had previously received didanosine (for > 3 months).
      The combination therapy was well tolerated, although grade 2-3 alopecia appeared
      in four patients who had very low CD4 cell counts (< 50 cells/mm3). No
      significant variation in renal, hepatic and pancreatic functions occurred. A
      significant reduction in the plasma HIV-1 RNA (> 0.5 logs) was observed in seven
      of ten patients naive to didanosine after weeks 4 and 12 of the study; five of
      these patients had a decrease in plasma HIV-1 RNA of > 1.5 logs, with two having
      a decrease of > 2.0 logs. The viral load became undetectable (below 200
      copies/ml) in three patients. The patients whose plasma HIV-1 RNA levels were not
      significantly reduced by the combination therapy had a higher baseline viral
      load. CD4 cell counts did not increase significantly in most patients. We
      observed a better response in those patients who had virus of the non-syncytium
      inducing phenotype. In conclusion, hydroxyurea in combination with didanosine was
      well tolerated and led to a reduction in viral load mainly in patients who were
      initially naive to didanosine.

PMID- 11322254
TI  - Impact of antiretroviral therapy on hepatitis C viraemia in HIV-infected
      patients.

PMID- 11322255
TI  - Decline of HIV-1 RNA in cerebrospinal fluid during zidovudine treatment.

PMID- 11322257
TI  - Replication of a pre-existing resistant HIV-1 subpopulation in vivo after
      introduction of a strong selective drug pressure.
AB  - Recent reports indicate a high rate of viral replication during all phases of HIV
      1 infection. This rapid turnover presents a continuous drive towards mutations in
      the HIV-1 genome, which may include those conferring drug resistance. Although
      the natural occurrence of drug-resistant variants has been reported, the
      implication on viral kinetics of the subsequent introduction of a selective
      pressure, in the form of antiviral treatment, remains to be elucidated. We
      analysed proviral DNA from nine previously untreated participants in a nevirapine
      study for the presence of the nevirapine resistance-conferring tyrosine to
      cysteine substitution at codon 181 of HIV-1 reverse transcriptase. In one
      individual, a minor proviral subpopulation containing this mutation was detected.
      A rapid selective outgrowth of this minor drug-resistant subpopulation during
      subsequent treatment with nevirapine was evidenced by a nearly complete
      replacement of the wild-type HIV-1 RNA population by 181-cysteine variant virus
      in serum within 1 week, and a reversal of the proportions of tyrosine- and
      cysteine-encoding proviruses within 2 weeks of treatment, which contrasted with
      other subjects tested. The rapid emergence of a drug-resistant virus variant
      clearly resulted in a lack of replication inhibition by nevirapine: whereas other
      patients demonstrated a median 1.2 log10 decrease in serum HIV-1 RNA load during
      the first week of treatment, an increase of 0.6 log10 was observed in this
      patient. The extensive repercussions for subsequent treatment of even a minor
      subpopulation of naturally occurring drug-resistant variants observed in this
      study must be considered in future therapeutic strategies.

PMID- 11322256
TI  - The impact of zidovudine compared with didanosine on health status and
      functioning in persons with advanced HIV infection and a varying duration of
      prior zidovudine therapy. AIDS Clinical Trials Group 116/117 Study Group.
AB  - The objective of this study was to compare the effects of zidovudine and
      didanosine on health-related quality of life in persons with advanced HIV
      infection and varying duration of prior zidovudine exposure. It was designed as a
      substudy nested in two similar placebo-controlled active-control-arm randomized
      trials, using sites of the AIDS Clinical Trials Group participating in the
      randomized trials of zidovudine versus didanosine (ACTG 116 and 117). The
      patients comprised 356 participants enrolled in ACTG 116 and 117. All had HIV
      infection and either a CD4 count of <200 cells/mm3, or a CD4 count of <300
      cells/mm3 plus symptoms of HIV disease. Participants were randomized equally
      within strata defined by duration of prior zidovudine therapy, to receive
      didanosine sachets at a dose of 500 mg daily (334 mg in subjects weighing <60 kg)
      or 750 mg daily (500 mg in subjects weighting <60 kg) plus inactive capsules
      resembling zidovudine, or to receive zidovudine capsules at a dose of 600 mg
      daily plus inactive sachets resembling didanosine. The main outcome measures were
      self-reported health-related quality of life, healthcare utilization, disability,
      work and symptom impact. The results showed no differences in reported symptom
      impact or healthcare utilization, and most measures of disability were similar.
      In the group with more than 8 weeks of prior zidovudine therapy, several of the
      health status scale scores for ongoing participants were significantly better for
      didanosine recipients, but average differences were small. Use of several
      different approaches to combining health status and survival showed no
      differences in the overall quality-time experiences between the treatment groups.
      Individuals taking zidovudine, low-dose didanosine and high-dose didanosine
      experienced 33, 34 and 35 weeks, respectively, in at least the typical health
      state if they had fewer than 8 weeks of previous zidovudine therapy, and had 23,
      23 and 26 weeks, respectively, if they had more than 8 weeks previous use of
      zidovudine. Results did not differ when data were analysed within strata
      ofpatients who had any versus no prior exposure to zidovudine, or AIDS versus non
      AIDS status. In conclusion, functional status and health-related quality of life
      were substantially similar among persons receiving either zidovudine or
      didanosine, regardless of the duration of prior zidovudine treatment.

PMID- 11322258
TI  - Evaluation of the efficacy and tolerance of R 018893, R 089439 (loviride) and
      placebo in asymptomatic HIV-1-infected patients. Loviride Collaborative Study
      Group.

PMID- 11322259
TI  - Intravenous ribavirin by constant infusion for serious influenza and
      parainfluenzavirus infection.
AB  - Three patients with severe lower respiratory tract influenza or
      parainfluenzavirus infections were treated with continuous ribavirin infusion,
      given as a 5 mg/kg/hour (h) loading infusion for 8 h followed by 1.5 mg/kg/h for
      2 to 6 days. This regimen was generally well tolerated. Plasma ribavirin
      concentrations were 40 to 60 microM in two patients during the continuous
      infusion phase and lower concentrations were detectable in tracheobronchial
      secretions. In temporal association with ribavirin administration, viral shedding
      diminished in one patient and ceased in two patients, one of whom had developed
      virus resistant to amantadine. The strategy of continuous ribavirin infusion
      warrants controlled testing for its antiviral and possible clinical
      effectiveness.

PMID- 11322260
TI  - A bend in the road--implications of ACTG 175 and Delta trials.

PMID- 11322261
TI  - Analysis of combinations of antiviral drugs and design of effective multidrug
      therapies.

PMID- 11322262
TI  - Selective cytotoxicity of lithium gamma-linolenic acid in human T cells
      chronically and productively infected with HIV.
AB  - We sought to extend observations of lithium gamma-linolenic acid (LiGLA)
      associated selective cytotoxicity in different models of chronic HIV infection in
      vitro. In our initial experiments, 8E5, 8E5L and A3.01 cells were allowed to
      proliferate in the presence of 0-20 microg/ml LiGLA for 4 days. Similarly, OM
      10.1 cells (with or without prior stimulation with tumour necrosis factor-alpha
      (TNF-alpha)) were grown with 0-5 microg/ml LiGLA for 10 days. Significant
      cytotoxicity was observed in productively infected 8E5 cells (100% cell death by
      day 2 at the highest concentration) as compared with latently infected 8E5L cells
      (50% cell death on days 2-4) and uninfected A3.01 cells. No drug-induced viral
      stimulation was observed in surviving cells. In fact, a mild direct antiviral
      effect may be present, independent of cytotoxicity. Maximum cytotoxicity to OM
      10.1 cells was only observed when active viral replication was induced by TNF
      alpha. Our preliminary results are encouraging and suggest that LiGLA should be
      retained as a candidate antiretroviral agent. Further work is underway to
      identify the specific mechanism underlying our observations.

PMID- 11322263
TI  - Early versus deferred zidovudine monotherapy: impact on AIDS-free time and
      survival in the multicenter AIDS cohort study.
AB  - The objective of this study was to compare the time to AIDS and to death between
      men receiving zidovudine therapy before or not before the diagnosis of AIDS. For
      the time to AIDS comparison, 821 men receiving zidovudine therapy before the
      diagnosis of AIDS were pair matched with men who did not receive zidovudine
      therapy until after diagnosis on their CD4 cell count (+/- 75 cells/mm3),
      haemoglobin level (+/- 0.75 g/dl), number of clinical symptoms and study visit at
      the time of initiation of zidovudine therapy and were monitored for a median of
      2.08 years. For the time to death comparison, 186 men who received zidovudine
      therapy prior to AIDS diagnosis were pair matched on the same variables to men
      who received zidovudine therapy only after the AIDS diagnosis, and were monitored
      for a median of 2.88 years. Only men with < 350 CD4 cells/mm3 who received
      zidovudine therapy prior to AIDS diagnosis remained AIDS free significantly
      longer than their pair match who did not (P < 0.0001). The median extension of
      time to AIDS was 0.61 years for men with < 200 CD4 cells/mm3 and 1.13 years for
      men with 200-349 CD4 cells/mm3. Cox regression analysis showed a significantly
      increased time to AIDS for the men with < 350 CD4 cells/mm3, both before and
      after adjustment for the use of prophylactic drugs against Pneumocystis carinii
      pneumonia. No difference was seen in the time to death between men receiving
      zidovudine therapy before or only after AIDS diagnosis. Zidovudine treatment of
      asymptomatic HIV-1-infected men provides significant benefit to men with < 350
      CD4 cells/mm3 by extending AIDS-free time, but does not extend survival. The
      analytical technique used is applicable to other observational studies of
      treatment.

PMID- 11322264
TI  - Hydroxyurea and didanosine is a more potent combination than hydroxyurea and
      zidovudine.
AB  - The in vitro and in vivo antiviral activity of hydroxyurea in combination with
      either zidovudine or didanosine was evaluated in primary human peripheral
      mononuclear cells and in a cohort of 29 asymptomatic patients infected with HIV.
      In vitro, hydroxyurea alone did not significantly affect HIV replication, whereas
      the combination of hydroxyurea with didanosine was more effective than the
      combination of hydroxyurea with zidovudine. Our clinical results confirmed these
      studies. Patients were randomly assigned to five arms (zidovudine, hydroxyurea or
      didanosine monotherapy, or hydroxyurea in combination with either zidovudine or
      didanosine) to evaluate preliminary safety and efficacy. Bone-marrow toxicity
      occurred in two patients treated with zidovudine plus hydroxyurea, alopecia was
      reported in one patient treated with hydroxyurea monotherapy, and there were no
      toxic effects recorded in the remaining three groups. Plasma viraemia was not
      influenced by hydroxyurea monotherapy, and the hydroxyurea-zidovudine combination
      did not give any advantage over either zidovudine or didanosine monotherapy (0.3
      0.5 log decrease in plasma viraemia). In contrast, a 1.1 log drop in plasma
      viraemia was observed in patients treated with hydroxyurea plus didanosine, this
      reduction was sustained throughout the 24-week course of the treatment.
      Combination therapy with hydroxyurea and didanosine exhibited statistically
      significant improvements compared with the other therapeutic approaches. Although
      further clinical trials are required, these results suggest that hydroxyurea in
      combination with didanosine might be an effective and well-tolerated, simple and
      affordable, treatment for HIV infection.

PMID- 11322265
TI  - Loss of antiviral effect owing to zidovudine and lamivudine double resistance in
      HIV-1-infected patients in an ongoing open-label trial.
AB  - In order to compare the resistance pattern to zidovudine plus lamivudine in
      zidovudine-experienced patients, we studied three HIV-1-infected patients
      enrolled in NUCB3004, an open-label trial. Over a 24-week follow-up, the patients
      were studied for drug sensitivity, reverse transcriptase genotype, viral load
      (HIV-1 RNA level) and viral phenotype (syncytium inducing (SI) or non-syncytium
      inducing). Virus isolates derived from peripheral blood mononuclear cells (PBMCs)
      were tested for changes in drug susceptibility. Proviral DNA in the patients'
      PBMCs and RNA from plasma and culture supernatant were subjected to amplification
      and sequencing. All three HIV-1 strains showed a decreased susceptibility to
      either zidovudine or lamivudine after 24 weeks of therapy. The pattern of DNA
      genotypic resistance to lamivudine in patient A showed a mutation at codon 184 of
      the reverse transcriptase-encoding gene (methionine to valine). No HIV-1 strains
      with lamivudine-related mutations in proviral DNA were found among the isolates
      obtained from patients B and C. In these two patients, the mutation at codon 184
      of the reverse transcriptase-encoding gene appeared in RNA, both in plasma and in
      culture supernatant. Viral phenotyping revealed the maintenance of the SI
      phenotype at week 24. Two out of the three patients experienced a reduction in
      HIV-1 RNA levels after 24 weeks of therapy, and in two out of three there was a
      rebound in viral load at week 28 together with the onset of the codon 184
      mutation in RNA. The degree of phenotypic resistance to both zidovudine and
      lamivudine correlated with the amino acid changes in RNA and the rapid increase
      in viral load.

PMID- 11322266
TI  - Once versus twice daily administration of didanosine in children with symptomatic
      HIV-associated disease who were intolerant to or clinically deteriorated on
      zidovudine. The Italian Pediatric Collaborative Study Group on Didanosine.
AB  - The objective of this study was to compare the safety, tolerability and clinical
      response of once- versus twice-daily administration of didanosine given at a
      dosage of 270 mg/m2/day in children with symptomatic HIV-associated disease who
      were intolerant to or clinically deteriorated on zidovudine monotherapy. We
      carried out a randomized, open-label multicentre trial. Didanosine was supplied
      in buffered tablets, which could be chewed or dispersed in liquid. The children
      were recruited from 16 paediatric departments participating in the Italian
      Register for HIV Infection in Children. A total of 53 children (median age 5.5
      years) started trial treatment; 26 were given didanosine twice daily and 27 once
      daily; 85% had AIDS and 98% had clinically deteriorated while on zidovudine
      therapy. Similar safety and tolerability results were demonstrated for the two
      schemes of therapy. A total of 11 children (20.7%) required discontinuation of
      didanosine for severe adverse events (five children (19.2%) in the twice-daily
      group; six children (22.2%) in the once-daily group, log-rank P = 0.81). Severe
      hepatic toxicity was uncommon (5.6%) while mild to moderate hepatic dysfunction
      was demonstrated in about 17% of the participants, without any difference between
      the two groups. Haematological toxicity was common (about 40% of the children, 11
      in the twice- and 19 in the once-daily group) but never severe. Clinical
      pancreatitis and retinal lesions were never demonstrated. There was no
      significant difference in progression to death or to a new opportunistic
      infection between the two treatment regimens (log-rank P = 0.54). The
      modification of surrogate efficacy parameters during the study period was similar
      in the two groups. However, weight gain was poorer in children treated once
      daily. This study suggests that the safety and tolerability of 270 mg/m2/day of
      didanosine given once daily is substantially similar to that of the traditionally
      recommended schedule of two divided doses. Owing to the small sample and to the
      severity of the clinical condition of the children enrolled, no definite
      conclusions on the comparative efficacy of the two regimens can be drawn.

PMID- 11322267
TI  - Zidovudine plus didanosine in primary HIV-1 infection.
AB  - Viraemia levels in the months following primary HIV-1 infection (PHI) predict the
      subsequent course of the infection. Inhibition of viral replication in PHI
      patients might improve their clinical prognosis. In this study, we evaluated the
      antiviral efficacy of the association of two reverse transcriptase inhibitors-
      zidovudine at 250 mg twice daily and didanosine at 200 mg twice daily--in 12
      patients treated for at least 6 months (median 10 months, range 6-15 months). We
      compared values for viraemia, proviral DNA and CD4:CD8 ratios in these patients
      with two historical control groups consisting of 16 untreated patients and 15
      patients on zidovudine therapy. Significantly lower viraemia was observed between
      3 and 12 months in patients on zidovudine-didanosine therapy. Viraemia levels
      lower than 200 HIV-1 RNA copies/ml were observed in 3/12 patients on zidovudine
      didanosine therapy after 3 months, in 8/12 after 6 months and in 3/5 after 12
      months. Only one of the 31 historical control patients had undetectable viraemia.
      For proviral DNA, smaller differences between groups were observed, although with
      time proviral DNA became undetectable (< 1 copy/7.5 x 10(5) lymphocytes) in four
      patients from the zidovudine-didanosine group versus one in the control groups.
      Finally, the CD4:CD8 ratio was significantly higher in the zidovudine-didanosine
      group and none of the patients in this group developed HIV-1-associated clinical
      complications. These data suggest a higher efficacy of combined therapy compared
      with zidovudine monotherapy in PHI patients and indicate that control of viraemia
      for at least 1 year is achievable in PHI patients.

PMID- 11322268
TI  - The first blow is half the battle.

PMID- 11322269
TI  - The role of didanosine in the management of HIV-1 infection.
AB  - Large-scale clinical end point studies comparing antiretroviral therapy with
      zidovudine alone, didanosine alone, and zidovudine combined with didanosine
      indicate that both didanosine alone and zidovudine/didanosine provide a better
      clinical outcome than zidovudine alone in patients with human immunodeficiency
      virus (HIV) infection. The superiority of combination didanosine/zidovudine
      therapy over zidovudine monotherapy was most significant in treatment-naive
      patients, but benefit was also seen in patients who had previously received
      zidovudine and also in all stages of disease. Activity marker data from other
      studies suggest that double or triple combination therapies that include
      didanosine and nucleoside analogues other than zidovudine, non-nucleoside reverse
      transcriptase inhibitors or protease inhibitors result in powerful suppression of
      viral replication that will provide additional clinical benefits. Apart from
      mostly mild gastrointestinal disturbances, didanosine alone and in various
      combination therapies has been generally well tolerated. Thus, didanosine
      represents a potent, versatile nucleoside analogue with potential benefits in
      both current and future antiretroviral regimens for HIV infection.

PMID- 11322270
TI  - Clinically relevant drug interactions with antiretroviral agents.
AB  - With the advent of the human immunodeficiency virus (HIV) protease inhibitors and
      the non-nucleoside reverse transcriptase inhibitors, the importance of drug-drug
      interactions with antiretroviral agents is becoming increasingly recognized.
      Every clinician involved in the care of HIV-infected persons should have a broad
      knowledge of these drug-drug interactions and their underlying mechanisms. This
      paper will review currently known clinically relevant interactions with
      antiretroviral agents reported thus far. Alternative strategies will be proposed
      where possible, in order to improve patient safety and the therapeutic efficacy
      of the antiretroviral agents. It must be emphasized, however, that in many cases
      these proposals are not backed up by authoritative clinical consensus panels and
      that clinical experience with many of these combinations is limited.

PMID- 11322271
TI  - Markers of response to zidovudine monotherapy among treated HIV seroconverters.
      Italian Seroconversion Study.
AB  - The aim of the study was to evaluate indicators of response to zidovudine
      monotherapy in terms of progression to AIDS and death in a cohort of human
      immunodeficiency virus (HIV) seroconverters. From a larger observational
      epidemiological cohort of 1,024 HIV seroconverters we identified 315 persons on
      zidovudine monotherapy. In this treated cohort, age, sex, risk group,
      constitutional symptoms, CD4 cell count, and p24 antigen levels at initiation of
      treatment and 6 months later were examined separately for two outcomes, AIDS and
      death, using standard survival methods. The variables measured at the visit at
      which zidovudine monotherapy was initiated that predicted more rapid progression
      to AIDS were CD4 cell count (RH = 2.61); constitutional symptoms (RH = 2.56); p24
      antigenaemia level (RH = 2. 17); and subsequent change in CD4 cell count (> 30%
      decline) contributed additional predictive information (RH = 2.70). Results were
      similar for mortality, and did not vary significantly by risk group. In a tested
      subset of patients, p24 antigenaemia was associated with high levels of plasma
      RNA viral load. The median number of HIV RNA copies was about 28,000 copies/ml
      among p24 antigen-positive individuals and about 7,700 copies/ml among
      participants who were persistently negative for p24 antigenaemia. CD4 cell count,
      symptoms and p24 antigenaemia at the start of therapy and CD4 cell decline after
      initiation of treatment are early indicators of disease progression in zidovudine
      treated patients. The combined use of these indicators may help to better predict
      who will respond to zidovudine or to other antiretroviral therapies.

PMID- 11322272
TI  - Reductions in viral load and increases in T lymphocyte numbers in treatment-naive
      patients with advanced HIV-1 infection treated with ritonavir, zidovudine and
      zalcitabine triple therapy.
AB  - In order to test the hypothesis that a combination of protease inhibitors with
      nucleoside analogues-agents known to inhibit different steps of the human
      immunodeficiency virus (HIV) life cycle--is likely to prove more effective in
      reducing viral loads than either of those modalities alone, we performed a 60
      week, open-label trial in 32 HIV-positive patients with depressed CD4 T
      lymphocyte cell counts but no active AIDS-defining illnesses. For the first 2
      weeks, patients received 600 mg twice daily of liquid ritonavir, a protease
      inhibitor; then zidovudine 200 mg three times daily and zalcitabine 0.75 mg three
      times daily were added to the treatment regimen. Mononuclear blood cell fractions
      were analysed for infected cell levels, using a co-culture system. HIV-1 RNA in
      plasma was measured both by reverse transcriptase-polymerase chain reaction (RT
      PCR) and reverse transcriptase quantitative PCR (QcRT-PCR); lymphocyte counts
      were determined by standard laboratory methods. In the 2 weeks of ritonavir
      therapy, both the mean count of infectious blood cells and plasma HIV RNA levels
      decreased dramatically. Mean CD4 cell counts increased from 173 cells/mm3 at
      baseline to 286 cells/mm3; CD8 cell counts rose from 951 cells/mm3 to 1,141
      cells/mm3. With the introduction of the nucleoside analogues, infectious cell
      counts and plasma virus dropped another log unit to a nadir at 8 weeks, while CD4
      T lymphocyte counts continued to rise slowly. By week 28, 12 patients had
      withdrawn due to adverse events, none of which were life-threatening. At week 36,
      infectious material could not be detected in the cells of 10 of the 17 remaining
      patients; by week 60, four of the seven patients with residual viraemia at week
      24 had undergone viral relapse. After the introduction of a more palatable
      capsule formulation of ritonavir at week 52, infectious cells and plasma virus
      were undetectable in 50-60% of patients. The combination of protease inhibitors
      and nucleoside analogues significantly reduces HIV load, and in some patients may
      suppress viral activity for sustained periods.

PMID- 11322273
TI  - Short-term efficacy and safety of stavudine in pretreated HIV-infected patients.
AB  - Most of the information available on stavudine (d4T) comes from studies in
      patients with advanced human immunodeficiency virus (HIV) disease to whom
      stavudine was administered as monotherapy. Herein, we summarize the results of
      adding 40 mg stavudine twice daily to previous therapies in patients with mild to
      advanced immunological disease (mean CD4 T cell count 178 cells/mm3; range 6-480
      cells/mm3). In an intention-to-treat, prospective, open trial, 64 patients (84.4%
      men; mean age 35.2 years) were analysed. Their average time on previous
      antiretroviral therapy was 19.8 months (range 6-52). Plasma HIV RNA load fell by
      a mean of 0.64 and 0.74 log at 1 and 3 months, respectively, after the start of
      stavudine therapy (P <0.001 Sign rank test). The CD4 cell count increased by a
      mean of 25.1 cells/mm3 in the third month (P = 0.002 Sign rank test). Antiviral
      activity was independent of the CD4 cell count at baseline, but more pronounced
      declines in viral load were seen in patients with shorter periods of previous
      antiretroviral therapy and in those in whom stavudine was combined with
      didanosine or lamivudine rather than zidovudine. Ten (15.6%) patients
      discontinued the drug during the first 6 months of treatment because of the
      development of toxicity (neuropathy in six cases, hepatitis in two, oedema in one
      and rash in another); all but one of them had CD4 counts < 200 cells/mm3. Another
      two patients stopped treatment voluntarily. The remaining 52 patients tolerated
      the drug well for the first 6 months and had a high level of compliance with
      treatment. In conclusion, stavudine is generally well tolerated and has
      significant antiretroviral activity when it is administered to patients with
      extensive previous treatment with multiple reverse transcriptase (RT) inhibitors.
      It should be expected that the short-term favourable effects of stavudine on
      laboratory markers will further translate into a reduced progression of disease
      and improved survival.

PMID- 11322274
TI  - Immunological and virological activity of zalcitabine and zidovudine in
      combination in HIV-positive people with CD4 cell counts of between 200-500
      cells/mm3.
AB  - We evaluated the effect of combination therapy with zidovudine (AZT) plus
      zalcitabine (ddC) in human immunodeficiency virus type 1 (HIV-1)-infected
      patients who had not previously received antiretroviral treatment ('naive'
      patients). The immunological and virological parameters evaluated were CD4 cell
      count, syncytium-inducing (SI) viral phenotype and plasma HIV-1 RNA copies/ml
      (HIV viral load). A total of 75 patients entered the study, with CD4 cell counts
      between 200 and 500 cells/mm3. All received zidovudine (200 mg) plus zalcitabine
      (0.75 mg) three times daily for 24 weeks. Treatment was well tolerated. However,
      four patients presented with anaemia (haemoglobin < 10.0 g/dl) and one patient
      had both anaemia and neutropenia (0.8 x 10(9) neutrophils/l). Combination therapy
      with zidovudine plus zalcitabine resulted in a pronounced improvement of
      virological and immunological markers. Approximately 25% of patients achieved
      undetectable plasma HIV RNA levels (< 200 copies/ml) at week 24. At the end of
      the study (24 weeks) a significant reduction (> 0.5 log) of plasma HIV RNA was
      observed in approximately 70% of patients and in 50% an even greater decrease (>
      1 log) was achieved. The most significant decrease in mean plasma HIV RNA levels
      was observed at week 4, whereas the highest increase in CD4 cell count was found
      at week 24. Approximately 80% of patients who showed baseline plasma HIV RNA
      levels below 20000 copies/ml had less than 5000 copies/ml at week 24. The plasma
      HIV RNA reduction observed at week 4 was significantly maintained at week 24.
      Therefore, we can rapidly select those who will not respond to therapy and adjust
      the treatment after a short interval. Our study supports the idea of early
      therapy because all patients who reached undetectable levels of plasma HIV RNA at
      week 24 had at baseline a median plasma HIV RNA load of 2560 copies/ml. In
      conclusion, zidovudine in combination with zalcitabine was well tolerated in the 
      majority of patients and led to a significant reduction in plasma HIV RNA copies
      in most of the patients with initial viraemia lower than 20000 copies/ml.

PMID- 11322275
TI  - HIV-1 RNA levels in the cerebrospinal fluid may increase owing to damage to the
      blood-brain barrier.
AB  - Human immunodeficiency virus type 1 (HIV-1) RNA can be detected in the
      cerebrospinal fluid (CSF) of 75-90% of all HIV-infected patients. However, it is
      not yet known which factors influence the amount of HIV-1 in the CSF, either
      qualitatively or quantitatively. We have analysed HIV-1 RNA in CSF samples from
      24 HIV-infected patients using zidovudine who underwent lumbar puncture in order
      to establish a diagnosis for a neurological disorder. Several factors were
      examined for possible correlation with the amount of HIV-1 RNA in the CSF: age,
      gender, the medical indication for lumbar puncture, the most recent CD4 cell
      count in blood, zidovudine dose, duration of treatment with zidovudine, the
      zidovudine concentration in plasma and CSF, and the total protein concentration
      in plasma and CSF. The only statistically significant factor was the total
      protein level in the CSF, which showed a positive relation with the amount of HIV
      1 RNA in the CSF. This study indicates that increased levels of HIV-1 RNA in the
      CSF of neurologically symptomatic patients are the result of damage to the blood
      brain barrier.

PMID- 11322276
TI  - Comparison of three different commercial methods for quantification of plasma HIV
      RNA in clinical specimens.

PMID- 11322277
TI  - Check, but not checkmate.

PMID- 11322278
TI  - Acyclovir in combination with zidovudine does not prolong survival in advanced
      HIV disease.
AB  - The aim of this study was to evaluate the association between acyclovir use and
      survival in HIV-infected patients. To achieve this, we used survival analysis in
      an observational cohort of HIV-infected patients enrolled in primary care at an
      urban HIV clinic. We measured survival in a cohort of HIV-infected patients who
      had CD4 cell counts < or = 500/mm3 and who enrolled for care at a single urban
      HIV clinic between December 1988 and April 1995. We compared survival in users of
      acyclovir alone, zidovudine alone, and acyclovir and zidovudine in combination
      with the survival of those using neither drug. Factors associated with improved
      survival were identified using Cox proportional hazards analysis. Among the 1408
      patients enrolled, there were no significant differences in overall survival
      between acyclovir users and non-users. After adjustment for CD4 cell count, the
      use of other antiretroviral agents, race, transmission risk and a history of
      herpesvirus infection, acyclovir use alone was independently associated with a
      relative hazard (RH) of death of 1.008 (P = 0.969); zidovudine use alone with a
      RH of 0.559 (P < 0.001); and combination use of acyclovir and zidovudine
      associated with a RH of 1.062 (P = 0.788). Therefore we conclude that the use of
      acyclovir is not associated with prolonged survival in this cohort of HIV
      infected patients.

PMID- 11322279
TI  - Results of long-term follow-up of HIV-infected patients treated with lamivudine
      monotherapy, followed by a combination of lamivudine and zidovudine.
AB  - The objective of this study was to determine the efficacy and safety of adding
      zidovudine to continuous treatment with lamivudine in symptomatic human
      immunodeficiency virus type 1 (HIV-1)-infected patients. Forty patients were
      monitored throughout lamivudine monotherapy and subsequent combination therapy
      with lamivudine and zidovudine, which was initiated because of disease
      progression, declining CD4 cell counts or prolonged use of lamivudine. Eleven of
      these patients had been treated with zidovudine before the start of the study.
      The median CD4 cell count at the start of lamivudine monotherapy was 200 x 10(6)
      cells/l. After a median interval of 69 weeks (range 23-102 weeks), the median CD4
      cell count had dropped to 110 x 10(6) cells/l. Initial improvements in all
      laboratory markers for antiretroviral efficacy were observed after the addition
      of zidovudine. The median CD4 cell count remained 18% above baseline after 48
      weeks of treatment with lamivudine and zidovudine, however plasma HTV-1 RNA load
      and CD4 cell counts returned towards baseline during prolonged treatment in most
      patients. The combination was well tolerated, although anaemia was observed in
      nine patients. Repeated measures analysis of variance suggested a superior effect
      of lamivudine monotherapy in patients who had previously used zidovudine. In
      conclusion, zidovudine was found to be effective in patients who have been
      treated with lamivudine. The study stresses the need to further define the
      mechanisms underlying this prolonged antiviral effect.

PMID- 11322280
TI  - Zidovudine treatment is not associated with HTLV-1 reverse transcriptase gene
      mutations in HTLV-I/HIV-1 co-infected patients.
AB  - Zidovudine treatment of human immunodeficiency virus (HIV) infection induces drug
      resistant viral strains harbouring specific amino acid substitutions in the
      reverse transcriptase (RT). To investigate whether this phenomenon could be
      observed in the case of human T lymphotropic virus type I (HTLV-I) infection, we
      analysed the HTLV-I RT proviral gene sequence in five HTLV-I/HIV-1 co-infected
      patients treated with zidovudine for HIV-1 infection and in one untreated co
      infected subject. In the 816 bp of HTLV-I pol gene sequence determined, no
      particular nucleotide mutation associated with zidovudine therapy could be
      identified in the treated subjects. Moreover, the dominant HTLV-1 deduced amino
      acid sequences determined in treated subjects were identical to that from the
      untreated subject. Our data show that in the co-infected patients already
      presenting well-defined mutations associated with zidovudine resistance in HIV-1,
      no mutations were observed in a part of the pol gene coding for the RT activity
      of HTLV-I.

PMID- 11322281
TI  - Viraemia and p24 antigenaemia are independent risk factors for the emergency of a
      zidovudine-resistant genotype in nucleoside analogue-treated HIV-1 infection.
AB  - We aimed to determine, in an observational retrospective study, whether baseline
      HTV-1 RNA is an independent predictive factor for the emergence of a genotype
      associated with zidovudine resistance and whether previously identified
      predictive factors remain independent when viraemia is taken into account. Fifty
      nucleoside-naive HIV-1-infected individuals initiating zidovudine therapy (in 11
      cases associated with didanosine) were submitted to clinical, immunological and
      virological monitoring at entry and every 12 weeks thereafter. The critical
      endpoint of the study was the influence of key baseline characteristics (CD4 cell
      counts, clinical stage, HIV-1 p24 antigen, virus phenotype and viraemia) upon the
      time to development of mutation at codon 215. The presence of serum p24 antigen,
      syncytium-inducing (S1) phenotype, a HIV-1 RNA load greater than the median
      (32495 RNA copies/ml), CD4 cell counts lower than 200/mm3 and clinical CDC
      category C were all baseline features associated with more rapid development of
      the mutant RT215 genotype in the univariate analysis. However, a multivariate Cox
      proportional hazard stepwise regression analysis showed that only baseline p24
      antigenaemia, SI phenotype and a HIV-1 RNA load greater than 32495 RNA copies/ml
      were sequentially selected as independent predictive factors for the development
      of the mutant genotype. The present study suggests that baseline HIV-1 RNA load
      is an independent predictive factor for the development of a zidovudine
      resistance genotype. Likewise, it reinforces the independent predictive value of
      serum p24 antigenaemia and SI phenotype, even when viraemia is taken into
      account.

PMID- 11322282
TI  - Different fibrillar architectures coexisting in Haversian bone.
AB  - Samples of compact bone were deproteinated by heat treatment and analysed by SEM.
      This technique removes very effectively cells and vascular structures and brings
      into full view the mineralization front along the wall of the Havers canal. The
      present study was confined to samples of equine bone that are known to be
      subjected to different functional requirements. Bone subjected to high tensile
      stress exhibited collagen fibrils substantially aligned with the stress
      direction, and the vast majority of its osteons appeared made of almost parallel
      fibrils crossing at very narrow angles. On the contrary, bone subjected to
      prevalent compressive forces showed either an orthogonal alternation of collagen
      lamellae, or a multidirectional arrangement corresponding to the twisted plywood
      described by other authors. Our observations substantiate the classical concept
      of the osteon structure as well as the twisted plywood; they indicate that
      several osteon architectures coexist in the same specimen, and that the different
      structures have a different preferential distribution in different parts of the
      same bone; and suggest that the relative distribution of the osteon
      ultrastructure across the bone matrix is modulated by mechanical factors.

PMID- 11322283
TI  - The structure of lungs and kidneys in the work of Malpighi.
AB  - This work documents the fundamental contribution to the knowledge of lungs and
      kidneys made by Marcello Malpighi. For the first time, in "De Pulmonibus", he
      described the pulmonary alveoli and the network of capillary perialveolar blood
      vessels, establishing definitively the existence of a communication between
      arteries and veins. Furthermore, he demonstrated that air does not enter the
      blood vessels, but that it makes contact solely with the thin walls of the
      delicate perialveolar vessels. Malpighi in "De Renibus" exactly described the
      microscopic anatomy of the cortex of the kidney, composed of renal glomerules.
      Then he explained the function of these minute structures where the urine is
      separated from the blood passing into the renal tubules.

PMID- 11322284
TI  - On the functional organisation of hyaline articular cartilage.
AB  - Function of agonists and antagonists and the centering effect of the muscles on
      the connected joint result in constant changes of the site of load. Based on a
      model it is assumed that chondric cells organise in form of "functional units"
      within the single layers of the hyaline tectorial cartilage. In each case a small
      number of those units is subject to the rhythm of load and relief in a fixed
      period of time given. After 24-hour-culture of small pieces of cartilage in Ham's
      F-10 medium erected cilia are found on the predominantly ciliated chondrocytes
      with this indicating relief of pressure. In these cells massive glycogen
      synthesis and an active Golgi apparatus are present. In parallel, chondrones are
      found in which cellular contact functions via a cilium. Time-dependent glycogen
      occurs in these cells too. Cells having almost the same synthesis time course of
      the glycogen join up to form "functional units", which are particularly involved
      in the biomechanic cartilage behavior in the radiar cell zone.

PMID- 11322285
TI  - Immunohistochemical detection of three serum protease inhibitors in mouse
      skeletal muscle by confocal laser scanning microscopy.
AB  - The tissue-associated counterpart of some plasmatic protease inhibitors has been
      studied in mouse skeletal muscle by combining immunoperoxidase confocal
      microscopy and Western blot analysis. To remove serum contamination all
      experiments were performed on C57 BL/10 adult mice perfused extensively with
      physiological solution under deep anesthesia. The following serum inhibitors were
      investigated in skeletal muscle by immunoperoxidase staining: alpha-2
      macroglobulin (alpha2M), antithrombin III (ATIII) and inter-alpha-trypsin
      inhibitor (ITI). The resulting localization patterns were analysed by laser
      transmittance scanning at 488 nm using a confocal microscope. Images obtained
      from a series of optical sections were then digitally intensified by a
      computerized program, allowing detection of even negligible amounts of
      immunoreaction product. In all muscles examined (soleus and extensor digitorum
      longus mm.) an extracellular (endomysial) localization was apparent for all
      inhibitors. By contrast remarkable differences were observed for the
      intracellular component: in fact alpha2M was present in about a half of the
      muscle fibers; ATIII was present inside all fibers; intracellular ITI was
      completely absent. Western blotting analysis of muscle homogenate was performed
      to biochemically characterize the above immunoreactivities. In preliminary
      experiments alpha2M-related immunoreactivity could not be found in the soluble
      fraction of perfused muscle, confirming an absence of serum contamination after
      in vivo perfusion. By contrast experiments on detergent-solubilized extracts
      (0.3% Triton X-100) revealed that tissue-bound alpha2M consisted of two main
      bands (168-166 KDa) and a minor component (35 KDa); ATIII of a single band (50
      KDA); ITI of four bands (180, 50, 45, 40 KDa). These results confirmed that the
      specific immunoreactivities visualized by morphological techniques corresponded
      to muscle-associated plasmatic inhibitors. The present data suggest that in mouse
      skeletal muscle i) numerous tissue-associated plasmatic inhibitors may protect
      the extracellular matrix from an excess of proteolysis; ii) a more restricted set
      of inhibitors may be also involved in the down-regulation of intracellular
      proteolytic processes.

PMID- 11322286
TI  - Effects of a tryptophan deficient diet on the morphology of skeletal muscle
      fibers of the rat. Preliminary observations at neuroendocrinological and
      submicroscopical levels.
AB  - It is proposed an animal model consisting of young male, L-tryptophan-deprived,
      namely 5-HT-free rats since their ontogenesis. This was obtained by feeding their
      mothers with a L-tryptophan-free (tf) diet since the day 1 of pregnancy. They
      were studied and compared with control rats of the same ages fed with a complete
      diet. Already at birth tf-litters were significantly underdeveloped as compared
      to the control newborn rats. Postnatal growth was in the tf-rats so poor that it
      worsened into a stricking dwarfism characterized by physical immaturity, muscular
      hypotrophy with alterations of motor activity and impairment of the hypothalamo
      pituitary-axis. A radioimmunological study of growth hormone (GH) showed in tf
      rats dramatic low plasma levels of the hormone, thus confirming the existence of
      serotonergic hypothalamo-pituitary pathways for GH in normal animals. By
      histological and ultrastructural examinations, hypotrophy and degenerative
      alterations of the muscle fibers could be observed. The possible causes for this
      finding are extensively considered and discussed.

PMID- 11322287
TI  - Microanatomy of the rat diaphragm with special reference to the lymphatics and
      mesothelial stomata.
AB  - The three-dimensional microstructure of the rat diaphragm was studied in order to
      reveal morphological bases which permit peritoneal fluids to pass across the
      diaphragm to enter the pleural cavity. The methods used include scanning electron
      microscopy of either intact or alkali-treated tissues, enzyme-histochemistry, and
      confocal laser scanning microscopy (CLSM). The peritoneal and pleural surfaces of
      the diaphragm are covered with mesothelial cells studded with numerous
      microvilli. There are many round gaps between mesothelial cells on the peritoneal
      side of the diaphragm. The subperitoneal connective tissue contains voluminous,
      irregularly shaped lymphatics which extended many funnel-shaped projections of
      the endothelia towards the pored region of the mesothelium. On coming into
      contact with the mesothelium, many of the lymphatic projections are perforated at
      their ends, thus giving rise to stomata connecting the peritoneal cavity and
      lymphatic lumen. Some projections ended blindly while plugging the mesothelial
      pores, thereby making visible some intercellular gaps in this contact. The
      subperitoneal sheet of collagen fiber network possesses clusters of pores which
      tightly fit the passage of the lymphatic projections. CLSM of the diaphragm after
      intraperitoneal injection of FITC-dextran has demonstrated the tracer both in the
      lymphatic lumen and in the connective tissue spaces. The tracer has also been
      detected in the lymphatics located in the subpleural connective tissue space.
      These results indicate that peritoneal fluid is allowed to flow into the
      lymphatics directly through the stomata and indirectly through the intercellular
      gaps between endothelia and mesothelial cells, and then drain into the subpleural
      lymphatics. Discussions were made on the probable mechanisms by which a
      hydrothorax may occur during continuous ambulatory peritoneal dialysis.

PMID- 11322288
TI  - Immunolocalisation of dystrophin in the immature human neurons and muscles.
AB  - Dystrophin, the product of the Duchenne muscular dystrophy gene, has been shown
      to be developmentally regulated in both human muscle and brain tissues. We
      consequently performed an immunocytochemical study using electron microscopy to
      localise the protein in the immature human fetal muscle and neurons. Results
      demonstrated that, even if dystrophin was partially associated to the plasma
      membrane in both tissues, some product was also linked to the neurofilaments
      network in neurons and to microfilaments in muscle. An intense staining was also
      found in satellite cells.

PMID- 11322289
TI  - Cell proliferation in the post-natal and adult mammalian central nervous system.
AB  - In the mammalian central nervous system cell proliferation is generally linked to
      developmental processes that are ultimated in the perinatal period. Few
      exceptions to this rule are known in certain regions of the mammalian brain,
      namely the post-natal cerebellar cortex and the adult subependymal layer. We
      report here the results of our studies about cell proliferation and related
      phenomena in these regions. Cell proliferation was visualised after
      bromodeoxyuridine incorporation and labeling of the proliferating cell nuclear
      antigen (PCNA), an endogenous protein expressed during the cell cycle. The
      occurrence of programmed cell death in the post-natal cerebellar cortex and the
      persistence of the embryonic isoform of neural cell adhesion molecule (NCAM)
      associated with proliferating cells in the adult subependymal layer were also
      investigated.

PMID- 11322290
TI  - Glial cells and blood-brain barrier in the human cerebral cortex.
AB  - The spatial relationship established between glial cells and microvasculature in
      the human cerebral cortex was analysed on peritumoral tissue of the parietal lobe
      removed during surgery. Observations performed by light microscope
      immunocytochemistry demonstrated that processes of astrocytes, strongly
      immunoreactive to both glial fibrillary acidic protein and S-100 protein, form
      sheaths to the capillaries, and that isolated cells positive to the
      oligodendrocyte marker 2',3'-cyclic nucleotide 3'-phosphodiesterase are
      detectable in perivascular areas. Morphometrical analysis by transmission
      electron microscopy showed that 80% of the vascular endothelium-pericyte layer is
      invested by small endfeet of astrocyte processes. This study demonstrates that
      either astrocyte bodies or oligodendrocytes as well as microgliocytes may
      substitute the astrocytic endfeet adhering to the capillary basement lamina.

PMID- 11322291
TI  - Models of neuronal plasticity and repair in the enteric nervous system: a review.
AB  - In the Fifties we developed an experimental model of neuronal plasticity in
      adulthood, involving the intestinal myenteric plexus. Causing an incomplete
      stenosis of the gut, the thickness of the wall and the diameter of the lumen
      underwent a massive increase on the oral side of the obstruction. The myenteric
      neurons innervating such hypertrophic and hyperplastic smooth muscle became
      hypertrophic and increased their number per ganglion, in absence of mitoses.
      Therefore we hypothesized the existence of a reserve pool of morphologically
      undifferentiated elements within the plexus, undergoing differentiation under
      conditions of functional hyperactivity. Some recent experiments suggest once
      again the existence in adulthood of a reserve pool of potential neurons. In fact,
      we put in evidence a subpopulation of NADPH-diaphorase positive myenteric
      neurons, very small in size orally to the stenosis and even smaller in the
      control gut. Following experimental ablation of the myenteric plexus in an
      intestinal segment and induction of hypertrophy in its smooth muscle layers, we
      found a two-five-fold increase in neuronal density along mesenteric nerves. This
      increase is probably due to the recruitment of cells, not readily identifiable as
      neurons, along mesenteric nerves in an attempt to reinnervate the damaged ileum.
      Moreover, it is demonstrated that hypertrophic smooth muscle cells may induce
      neuronal differentiation of transplanted PC12 cells. Finally, we explain the
      decreased total number of myenteric neurons in advanced age with the exhaustion
      of this reserve pool: in fact, NADPH-diaphorase positive small neurons in the
      myenteric plexus of old rats could not be found.

PMID- 11322292
TI  - Sensor cells and nerve terminals in some gut-derived organs: a review.
AB  - The intestinal mucosa is supplied with intraepithelial sensor paraneurons and
      with nerve fibers restricted in the lamina propria. The present study compares
      some gut-derived and -related organs in regard to their neuroparaneuronal
      elements deviated in structure and function from those in the gut. At the light
      microscopic level the urethra contains intraepithelial sensor paraneurons with
      ramified cell base containing serotonin and sensory nerves penetrating the
      epithelium to reach the lumen. The trachea and bronchi contain, besides sensor
      paraneurons, numerous sensory nerves within the basal layer of the epithelium.
      These nerves are proposed to form a sensory complex, being associated with the
      epithelial cells. The respiratory portion of the nasal mucosa lacks
      intraepithelial paraneurons, while revealing numerous sensory nerves passing
      through the epithelium to directly detect stimulants in the air.

PMID- 11322293
TI  - GAP-43 in the spinal trigeminal and dorsal column nuclei of the newborn and adult
      man: immunohistochemical distribution and comparison with that of the
      neuropeptides SP and CGRP.
AB  - By means of immunohistochemistry the presence of the growth-associated protein
      GAP-43 and its codistribution with substance P (SP) and calcitonin gene-related
      peptide (CGRP) are studied in the human spinal trigeminal, gracile, and cuneate
      nuclei at perinatal and adult life stages. The results obtained show that the
      distribution pattern of GAP-43 in the areas examined varies with age and that the
      immunohistochemical detectability of the protein persists in discrete subregions
      of the trigeminal and cuneate nuclei of the adult, where its localization closely
      matches that of SP and CGRP. It is suggested that neuronal plasticity may be
      pronounced throughout life in areas of the human nervous system involved in the
      neurotransmission of protopathic stimuli at the first synaptic level. Discrete
      subregions of the cuneate nucleus, bearing neurochemical characteristics
      strikingly similar to those of the substantia gelatinosa of the trigeminal
      subnucleus caudalis are pointed out.

PMID- 11322294
TI  - Study of genome organization by DNA cytochemistry and fluorescence imaging: a
      review.
AB  - DNA analysis by quantitative cytochemistry has been a widely exploited approach
      to investigate chromatin superstructural changes in relation to cell function and
      cell cycle progress. To this aim, a number of dyes (especially fluorochromes) for
      nucleic acids have been used, exhibiting different peculiarities, in terms of
      both binding mechanism and base specificity. Less attention has been paid to the
      application of different DNA staining techniques for studying possible
      differences in genome organization among different taxa. The purpose of this
      paper is to review and discuss the present reports in the literature, concerning
      the cytochemical analysis of genome organization, in a comparative perspective.
      Special attention is given to the integration of quantitative studies based on
      cytofluorometric and imaging techniques.

PMID- 11322295
TI  - Comparative morphological study of the normal human lens and the cataract by
      scanning electron microscopy.
AB  - The human lens is an important part of the anterior segment of the eye because of
      its transparency and its refractive power. These special features of the lens
      depend on the special arrangement of its cellular elements, the lens fibres. The
      morphology of these fibres, their cellular integrity, the interfibrillar junction
      mechanisms and their spatial arrangement deteriorate with age because of complex
      biochemical and biophysical phenomena. All these factors cause a general disorder
      in the morphology of the various layers of the lens that will finally lead to the
      loss of the characteristic transparency and the concomitant development of a
      cataract.

PMID- 11322296
TI  - Mechanisms of secretory granule transport and exocytosis in anterior pituitary
      cells.
AB  - Mechanisms of secretory granule transport and exocytosis in anterior pituitary
      cells were studied using various electron microscopic techniques. Some secretory
      granules were linked with microtubules by short strands. Many thin filaments were
      associated with all the secretory granules as well as membrane organelles.
      Adjacent granules were interconnected by these filaments. Some of the granule
      associated filaments were proved to be actin filaments. Microtubules and granule
      associated filaments must be involved in the secretory granule transport.
      Secretory granules were not located just under the plasma membrane where abundant
      actin filaments occupied the subcortical cytoplasm, while a lot of granules were
      in close contact with the plasma membrane in the region free of the subcortical
      actin filaments. This indicates that the subcortical actin filaments regulate the
      granule access to the plasma membrane. Secretory granules just beneath the plasma
      membrane were linked to it by intervening strands with various length. Annexin
      II, one of the Ca2+-dependent phospholipid binding proteins, was mainly
      associated with the plasma and granule membranes, especially localized at their
      contact sites. Annexin II might be one of the components of the intervening
      strands, and play an important role in the membrane contact and fusion.
      Exocytotic process was visualized by the quick-freeze, deep-etch electron
      microscopy. The initial membrane fusion starts with formation of a cylindrical
      neck-like structure. The intervening strands still link between the plasma and
      granule membranes during the membrane fusion.

PMID- 11322297
TI  - The pineal body of the mink and horse with special reference to the reproductive
      cycle. An ultrastructural and immunocytochemical study.
AB  - An ultrastructural and immunohistochemical analysis was performed on the
      epiphysis of two species of mammals: mink and horse. These animals present a
      reproductive cycle that varies along the year according to the light exposition.
      The aim of the study was to define possible structural changes connected with the
      gonadal activity. Structural aspects in common emerged such as those in concern
      with the epiphysis cells, their immunocytochemical characteristics (NSE and
      Synaptophysin positivity of pinealocytes, as well as CFAP positivity of further
      cells), and those in concern with the general ultrastructure. This latter has in
      particular revealed significant differences in relation to the biological cycles
      considered. In the presence of gonadal activity the mink pinealocyte displays a
      modest cytological organization which, on the contrary, after the mating and in
      arrest of the gonadal activity, appears as fully restored. In the horse, in both
      natural and artificially induced photoperiods, significant variations were noted
      these in connection with the various phases of development of the electron-dense
      granules, typical of the horse pinealocyte, interpreted as melanosomes. These
      aspects confirm the role of the epiphysis in the regulation of the reproductive
      cycle, albeit in the presence of species-specific peculiarities.

PMID- 11322298
TI  - Is the spleen a preferential site of blood cell production in the human fetus?
AB  - Information about the status of the spleen as a preferential site of blood cell
      production in the human fetus is relevant to generalizations about the ontogeny
      of haematopoietic microenvironments and to speculations about the pathogenesis of
      myeloid metaplasia. Such information has been accumulated in a comparison of
      populations of blood cell precursors derived from the blood, the spleens and the
      livers of human fetuses during the fourth, fifth, sixth and seventh months of
      gestation. During this period, the spleen does not contain populations of
      erythroblasts or granulocyte precursors that could not have been derived from the
      blood. It is inferred that in the human fetus the spleen is not a preferential
      site of blood cell production between the fourth and seventh months of gestation.
      Like any other site, the spleen may however accommodate intravascular blood cell
      precursors, which may proliferate and differentiate in human fetal blood.

PMID- 11322299
TI  - T and B lymphocytes in AIDS. Morphological aspects.
AB  - This paper presents scanning electron microscopic features of T and B Lymphocytes
      in patients affected with AIDS and ARC and compares these results with others
      obtained in patients showing an immunodeficiencey associated with therapy for
      oncological diseases and in normal healthy donors. The SEM observations showed
      some surface alterations of the lymphocytes consisting in protrusions, buddings
      and characteristic "bowl-shaped" cavities particularly evident on the
      lymphocytes' surface of end stage patients suffering from AIDS. Similar aspects
      were not found in the other groups including the healthy donors. These lymphocyte
      surface alterations might likely correspond to the first sign of cell disfunction
      and therefore represent an early marker of this complex disease.

PMID- 11322300
TI  - Early endocardial formation originates from precardiac mesoderm as revealed by QH
      1 antibody staining.
AB  - The formation of endocardial endothelium in quail embryos was investigated using
      in vivo and in vitro systems. At stage 7+ (2 somite), the initial emergence of
      endothelial cells within the bilateral heart forming region (HFR) was detected in
      quail embryos by immunohistochemistry with QH-1 (an anti-quail endothelial cell
      marker) and confocal microscopy. We consistently observed more QH-1 positive
      cells in the right HFR than the left. At stage 8 (4 somite), the HFR, including
      QH-1 positive cells, were located in the splanchnic mesoderm after formation of
      the coelom. During stage 8, the HFR migrated along the margin of anterior
      intestinal portal in association with the endoderm. By stage 8+ (5 somite), the
      two HFR had fused at the midline and formed a plexus of QH-1 positive endothelial
      precursor cells. The definitive endocardium developed as a single, hollow, tube
      within this plexus. Posteriorly, QH-1 positive cells of the HFR established
      vascular-like connections with QH-1 positive cells that had formed outside
      (peripheral to) the HFR. During migration and subsequent determination, the
      precardiac mesoderm is continuously associated with the basement membrane of the
      anterior endoderm. To determine the role of endoderm on endocardial endothelial
      cell formation and development, precardiac mesoderm from stage 5 embryos, which
      does not express QH-1 antigen, was explanted onto the surface of collagen gels.
      When co-cultured with endoderm, the outgrowth of free cells from the mesoderm was
      much more extensive, many of which invaded the gel and expressed the QH-1
      antigen; mesoderm cultured without endoderm did not seed nor express QH-1
      antigen. These findings suggest that the segregation of endothelial and
      myocardial lineages may occur by an endoderm-mediated, mesenchymal formation.

PMID- 11322301
TI  - Ultrastructural and morphometric features of nodal and impulse-conducting cardiac
      myocytes of the bat Pipistrellus pipistrellus.
AB  - Cells of the impulse-generating and conducting tissues of the insect-eating bat
      Pipistrellus pipistrellus were studied and evaluated using ultrastructural
      morphometry. Sinoatrial node cells are smaller than working atrial cells and
      measure about 6.5 microm in diameter. Their mitochondira and myofibril content
      constitute 23% and 19% of cytoplasmic volume, respectively. Corresponding values
      for working atrial cells are 23% and 52%. Atrioventricular node cells are 4.2
      microm in diameter and contain abundant glycogen in the cytoplasm. The fractional
      volume of mitochondria in about 24% while that of myofibrils is 7%. Cells of the
      bundle of His are larger (6-8 microm diameter) and contain more cellular
      organelles than do nodal cells. Their mitochondria and myofibril contents are 25%
      and 25%, respectively. Cells in the proximal part of the right bundle branch are
      slender with diameters averaging 3.4 microm. Mitochondrial content is 23% while
      myofibrils occupy 20% of the cytoplasmic volume of these cells. Distally located
      bundle branch cells measure 7-10 microm in diameter with mitochondria and
      myofibril volumes of 30% and 33%. Subendocardial cells in the ventricular free
      wall are large reaching 28 microm in diameter (cf. 14-18 microm in working
      ventricular cells) and have mitochondira and myofibril volume fractions of 32%
      and 29%, respectively (35% & 40% for working ventricular cells).

PMID- 11322302
TI  - The transendothelial passage in the absorbing peripheral lymphatic vessel of the
      rodent diaphragm.
AB  - The absorbing peripheral lymphatic vessels of rat (Wistar/Kyoto) and gerbil
      (Meriones unguiculatus) diaphragms were observed with SEM, TEM and three
      dimensional models under normal conditions, after experimental hemorrhage and
      after abdominal injection of China ink and latex polystyrene particles.
      Superficial and deep lymphatic vessels were noted and their ultrastructural
      characteristics showed an endothelial wall lacking a continuous basal lamina.
      Moreover, "intraendothelial channels" which are dynamic, fundamental pathways for
      lumen migration into the lymphatic vessel for fluids, China ink and latex
      polystyrene particles, were also demonstrated. Concerning the transendothelial
      passage of the autologous erythrocytes after their migration through the stomata
      and submesothelium connective channel, it was observed that this passage occurs
      by means of a "transcellular pathway". This consists of a "migratory pore"
      independent from the intercellular junctions, which is formed by an active
      process following a probable immunological response or cellular interaction
      between the erythrocyte and the endothelial cell.

PMID- 11322303
TI  - Enzyme histochemical studies on tumor blood vessels.
AB  - The oxygenation, the growth rate and the metastatic potential of a solid tumor
      depend on its vascularization and, in particular, on angiogenesis; a therapeutic
      approach affecting angiogenesis has been suggested as an alternative to
      conventional ones. Especially the study of the metabolism in the cells of the
      vessel wall should be a useful prerequisite for this approach. In this
      connection, an enzyme histochemical study was performed to characterize the blood
      vessels in a solid tumor (Ehrlich carcinoma). The following enzymes were
      considered: (a) alkaline phosphatase, involved in the transcellular phosphate
      transport and in the response to inflammatory and growth promoting factors; (b)
      dihydrofolate reductase, involved in the metabolism of tetrahydrofolate (for the
      synthesis of nucleic acids and the metabolism of serine and glycine); (c) purine
      nucleoside phosphorylase, involved in the degradation of purines and, in
      particular, of extracellular ATP and ADP; (d) xanthine oxidoreductase, engaged in
      the same degradation path and leading to the formation of urate, a strong
      antioxidant. Various patterns of enzyme activities were observed in the vessel
      wall. In particular, thin linear capillaries (presumed to be host capillaries
      penetrating the tumor) were identified for the intense positivity of alkaline
      phosphatase, dihydrofolate reductase and purine nucleoside phosphorilase;
      tortuous capillaries with variable diameters (presumed to be induced by
      angiogenesis from the host vessels) were negative for the alkaline phosphatase
      and expressed an heterogeneous pattern for the dihydrofolate reductase. All the
      data suggest a different vessel behaviour concerning the response to cytokines
      and to inflammatory stimuli.

PMID- 11322304
TI  - Marcello Malpighi: the father of microscopic anatomy.
AB  - Biographical data of Malpighi to justify naming him "the father of microscopic
      anatomy", as he used the microscope, soon after its invention, to study and
      discover and accurately describe many biological, particularly anatomical,
      structures. Although he utilized the microscope as a scientific instrument, his
      ideas, innovations and discoveries caused such an opposition that the microscope
      could be considered as Malpighi's weapon to start a scientific revolution. He was
      a naturalist for whom the "natural world, known and experienced scientifically,
      was all that existed". He was also a "cardiocentrist", who opposed Galen's
      "hepatocentrism". Several anatomical structures known eponymically to honor
      Malpighi are listed followed by their synonyms. Malpighi is another example of a
      genius as an extraordinary man who stood on the shoulders of giants, such as
      Galilei, Hans and Zacharias Janssen, Borelli, Harvey, B. Massari, among others.

PMID- 11322305
TI  - Morpho-functional aspects of human placental vessels.
AB  - This study reports some morphological characteristics of human placenta that play
      an important physiological role in normal pregnancies. The structures were the
      spiral arteries, the extracellular matrix and the MHC-antigens bearing cells. We
      studied these important tissue compartments in 80 placentas from normal and
      abnormal pregnancies (affected by in utero growth-retardation), where we could
      hypothesize an altered pattern of the same structures. Placental specimens were
      evaluated using histochemistry and immunohistochemical methods, like echo-doppler
      and echography. Our data show uterine and spiral arteries as markedly changing
      during pregnancy in normal women, but surely involved in some different
      morphological alterations in the pathological groups. The extracellular matrix
      compartment is strictly related with the vascular one, both under a physiological
      point of view (artery resistance and sometimes blood flow inversion) and under a
      non-cellular component pattern. Normal specimens are rich in sialomucins,
      solfomucins and glycoproteins. Collagen bundles are mainly of fetal type III, by
      also adult type I is present at the physiological end of pregnancy. In placentas
      with blood supply alteration, morphological studies suggest an early aging of the
      extracellular matrix (with prevalence of adult type I collagen in perivascular
      muffs). These changes could make more difficult all the exchanges from the blood
      to the tissues. The immunocompetent cell population is normally well represented
      in placental tissue: these cells are dentritic-shaped and lie in the perivascular
      spaces and in the placental and villous stroma. In the altered placentas
      examined, we were able to identify HLA-DR+ cells that exhibit Langerhans cell
      markers and are strongly suggestive of an alteration of the normal immunitary
      relationship between fetal antigens and mother T-cell populations.

PMID- 11322306
TI  - High resolution detection of human metaphase chromosomes.
AB  - The new generation of field emission in lens scanning electron microscopy with
      the sample located within the objective lens allows the observation of uncoated
      biological samples. Here we describe HeLa metaphase chromosomes isolated by two
      procedures and the localization within these chromosomes of a DNA centromeric
      probe. Chromosomes isolated in methanol acetic acid show 10 nm fibers organized
      in a three dimensional network while the structure of chromosomes obtained by the
      polyamine method's characterized by very dense short protusions of 30-50 nm in
      thickness. In situ hybridization with a DNA centromeric probe revealed by
      colloidal gold particles demonstrate that the hybridization occurs at the level
      of the 10 nm fiber with a high definition in the localization of specific DNA
      sequences.

PMID- 11322307
TI  - The peptidergic innervation of human coronary and cerebral vessels.
AB  - It is now well established that in addition to nerves containing classical
      transmitters, the mammalian vascular system is also supplied by nerve fibre
      subpopulations containing several vasoactive peptides. The precise function of
      these peptides (neuropeptide Y, calcitonin gene-related peptide, vasoactive
      intestinal polypeptide, somatostatin and the tachykinins) is still unknown,
      however, their widespread occurrence in perivascular nerves indicates that they
      are likely candidates for a role in the neurogenic regulation of the vascular
      system. It has been suggested that they may exert a direct vasomotor action via
      their own receptors and/or modulate the release and action of other vascular
      transmitters. Recently, several studies have focused on the supply of nerve
      fibres storing neuropeptides in the coronary and cerebral vasculature of
      laboratory animals, however, little is known on the distribution of these
      putative transmitters in human coronary and cerebral vessels. In this paper, the
      immunocytochemical evidence that several neuropeptides are localized in
      subpopulations of afferent and efferent nerve fibres supplying the human coronary
      and cerebral vasculature is focused.

PMID- 11322308
TI  - Ultrastructural immunolocalization of enamel matrix proteins during early stages
      of ameloblast differentiation.
AB  - Enamel matrix proteins (EMP) represent specific molecular markers of ameloblast
      secretion. In order to study early differentiation stages of the cells of the
      inner enamel epithelium, we have investigated the ultrastructural localization of
      EMP-immunoreactivity in rat tooth germ. Pre-secretory stages of ameloblast
      differentiation were identified by the absence of EMP-immunoreactivity within
      epithelial cells as well as adjoining extra-cellular matrix. During subsequent
      secretory stages EMP-like immunoreactive material could be detected both within
      epithelial cells as well as within the adjoining extra-cellular matrix. The
      intensity of the immunoreactivity increased while advancing with the
      differentiation of epithelial cells. Intracellularly, EMP-immunoreactivity was
      detectable in cytoplasmic compartments involved in exocrine secretion pathway.
      During the early secretory stage, EMP-immunoreactive material was also detectable
      in the basement membrane of the epithelial-mesenchymal interface and within the
      pre-dentine, close to odontoblast plasma membranes and processes. It is thus
      suggested that EMP may cross the basement membrane between epithelial and
      mesenchymal cells. Our study suggests that this aspect might be important in
      molecular mechanisms that regulate epithelial-mesenchymal interactions during
      odontogenesis.

PMID- 11322309
TI  - Fine structure of healthy human gingival mast cells and their immunological
      characterization.
AB  - Despite the great number of studies on mast cell population, at the present time
      few are the studies regarding the structural aspects of mast cells in human
      gingiva. In order to identify and characterize gingival mast cells, specimens of
      healthy human gingival tissue have been studied. Subsequently, in order to test
      mast cell capability of express TNF-alfa, samples of healthy gingiva with
      antibody anti-TNF-alfa have been incubated. The results showed that in human
      gingiva mast cells are numerous and ubiquitarious. These cells exhibit several
      morphological types of cytoplasmic granules with characteristic subgranular
      content, varying in shape and density. This allows to divide gingival mast cells
      into two different subpopulations: either cells containing granules with compact
      coiled scrolls and/or particles and cells showing granules with scrolls and thin
      parallel bands. The two ultrastructural aspects observed seem to be correlated to
      the McT (mast cells containing tryptase) and McTC (mast cells containing tryptase
      and chymase) described in international literature, differing for ultrastructural
      aspect, biochemical content and response to secretagogue substances. The
      positivity of the reaction for TNF-alfa seems indeed to confirm that gingival
      mast cells are able to secrete sensible amounts of TNF-alfa.

PMID- 11322310
TI  - Comparative observations on lingual papillae and their connective tissue cores in
      three primates. A scanning electron microscopic study.
AB  - The 3-D structure of the connective tissue cores (CTCs) of the lingual papillae
      in three primates (treeshrew, crab-eating monkey and man) was observed by
      scanning electron microscopy. Each filiform papilla has some slender protrusions
      on the top in the three kinds of primates. After removal of the epithelium, the
      CTC of the filiform papillae has a columnar primary core with some rod shaped
      secondary protrusions whose number and size vary among the three species. The
      number of secondary protrusions on the filiform CTC is generally small in the
      treeshrew and is the greatest in man. The stereo structure of the filiform CTC is
      fundamentally similar in all these three species and is different from those of
      other animal orders (i.e. Insectivora, Rodentia etc.). The fungiform CTC in man
      as well as in the crab-eating monkey is coralliform in shape and branched several
      times with small depressions for taste buds on the top of each one, though there
      were some differences between the two species in stereo structure. On the other
      hand, the fungiform CTC in the treeshrew was columnar in shape and was rather
      similar to that of Insectivora and Rodentia. In the treeshrew there are several
      finger-like processes in the region where foliate papillae are located in man as
      well as in the crab-eating monkey.

PMID- 11322311
TI  - Morphostructural characteristics of the vallate papillae in Bos taurus.
AB  - The Morpho-structural characteristics of the vallate papillae of the bovine
      tongue were studied utilizing LM, SEM and TEM techniques. In the bovine, the
      vallate papillae are numerous and different in size. They have a prominent vallum
      papillae which surrounds a deep sulcus papillae. The sulcus has many elongated
      taste buds on its inner wall. Nervous fibers enter the taste bud and sometimes
      have rosary shaped axons. The gustative sensitivity of these animals may be
      instrumental, in their choice of food and avoidance of noxious plants.

PMID- 11322312
TI  - The intracellular structure of secretory and ductal epithelia of human major
      salivary glands. A scanning electron microscopic study.
AB  - The secretory and ductal cells of human salivary glands have been studied at
      Scanning Electron Microscopy (SEM) by our modification of the Aldehyde-Osmium
      DMSO-Osmium (A-ODO) maceration method which enables the analytical study of human
      bioptical specimens. The most interesting results are those concerning the
      visualization of the cytoplasmic aspect of intercellular canaliculi of serous
      cells and of mitochondria of ductal cells. The canaliculi appear as elongated
      cylindrical structures fenestrated by holes correspohding to the bases of
      microvilli deprived of the cytoskeleton. Mitochondria of principal cells are
      longer and more complex than previously reported.

PMID- 11322313
TI  - Scanning electron microscopy study of the palatine salivary glands of rabbits.
AB  - The structure of the palatine salivary glands of rabbits was studied employing
      scanning electron microscopic methods. The fractured surface of the palatine
      salivary glands revealed that they were formed of small lobuli separated by
      interlobular spaces containing numerous bundles of collagen fibers. The NaOH
      treated specimens showed the organization of the collagen fibrils in their
      original location. In the interstitial stroma compartment, the collagen fibrils
      revealed a complex three-dimensional arrangement forming channel-like structures
      for supporting nerve fibers, small vessels and capillaries. Single groups of
      acinar cells were clearly demonstrated, and each acinus was enveloped by a
      characteristic basal lamina showing a sponge-like structure made up of several
      interconnected meshes of collagen fibrils. Furthermore, taking advantage of the
      ODO method and field emission scanning electron microscopy, within the cytoplasm
      of secretory acinar cells numerous organelles were clearly observed in a three
      dimensional way such as Golgi complex lamellae, rough endoplasmic reticulum,
      mitochondria and secretory granules. All these cytoplasmic components revealed
      their real and microtopographical arrangement in some areas of the acinar
      cytoplasm clearly suggesting their direct involvement in energetic as well as
      secretory activities.

PMID- 11322314
TI  - The interstitial cells of Cajal of the rat stomach. A light and electron
      microscope study.
AB  - Interstitial cells of Cajal (ICC), presumed to have a smooth muscle-like nature
      and to play a pacemaker role, are usually identified for their peculiar
      ultrastructural features and specific location throughout the gut muscle wall. A
      Zinc-Iodide-Osmium (ZIO) impregnation for ICC identification under the light
      microscope has been proposed. However, controversies as to certain ICC
      identification under both light and electron microscopes are still present, due
      to their ultrastructural features somewhat similar to the fibroblast ones and the
      low specificity of the ZIO-staining. The rat stomach has been studied. Some
      specimens have been routinely processed for electron microscopy, some others have
      been ZIO-impregnated and further routinely processed for both light and electron
      microscopy, in order to assure that all the cells presumed to be ICC for their
      ZIO-staining affinity are the same cells identified as ICC with routine electron
      microscope procedures, and not fibroblasts. The routine electron microscope
      examination made it possible to identify within the rat gastric muscle coat two
      cell populations, one with the same location and morphology as those reported in
      literature for the gastric ICC, and a second one with a similar location, but
      showing undoubted fibroblastic features. ZIO-staining, under both light and
      electron microscopes, revealed ZIO-stained cells distributed within the muscle
      coat in a manner identical to that of the ultrastructurally identified ICC. Under
      electron microscope examination, this cell type only was fully impregnated by the
      zinciodide deposits, whereas all other cell types, including fibroblast-like
      cells, were devoid of them. These data confirm that ICC can be electively ZIO
      stained and that these cells and fibroblasts are two distinct cell types, as
      ultrastructural and physiological reports had previously suggested.

PMID- 11322315
TI  - Ultrastructural organization of the sperm nuclear matrix.
AB  - The organization of DNA-protamine complexes and their association with the
      nuclear matrix have been analyzed in sperm nuclei by in situ Nick Translation at
      the electron microscope. The data obtained indicate that the chromatin
      organization in sperm nuclei is maintained during the sperm condensation by means
      of interaction with the nuclear matrix at fixed sites. The fine structure of the
      sperm nucleus and sperm nuclear matrix, investigated by sectioning and replica of
      freeze-fractured specimens, suggests that the lamellar array observed by freeze
      fracturing in the sperm nuclei, could depend on the inner matrix which presents a
      regular organization of globular structures involved in the maintenance of
      chromatin domains.

PMID- 11322316
TI  - Ultra-high-resolution scanning electron microscopic studies on the membrane
      system of the rat parietal cells after tetragastrin stimulation.
AB  - The membrane system of the rat parietal cells in the resting state and after
      stimulation with tetragastrin (gastrin) was examined by ultra-high-resolution
      scanning electron microscopy after removal of the cytoplasmic matrix by the
      aldehyde-osmium-DMSO-osmium procedure. The intracellular canaliculus was lined
      with numerous microvilli. Viewed from the cytoplasmic side, the intracellular
      canaliculi appeared as an arborized system of cactus-like structures with
      numerous holes about 100 nm in diameter corresponding to the basal openings of
      the microvilli. The intracellular canaliculi were more developed after gastrin
      stimulation than in the resting state. In resting cells, most of the
      tubulovesicles were isolated, 100-200 nm in diameter, spherical or tubular in
      shape. After gastrin stimulation, these structures were interconnected by slender
      tubules of about 30 nm in diameter forming together tubulovesicular network.
      Stereo SEM views clearly demonstrated that the tubulovesicular network was
      connected with the intracellular canaliculus by the slender connecting tubulus.
      The increase in the canalicular membrane area and the depletion of tubulovesicles
      is explained by the transfer of the tubulovesicular membrane to the intracellular
      canaliculus. In the resting parietal cell, the microvilli are slender and their
      interior is packed with microfilaments. After gastrin stimulation, the microvilli
      are swollen and their interior is edematous. These morphological changes seem to
      indicate the accumulation of fluid in the microvilli after gastrin stimulation.

PMID- 11322317
TI  - Phylogenetic study on distribution and chromogranin/secretogranin content of
      histamine immunoreactive elements in the gut.
AB  - The distribution of histamine-immunoreactive (HA-IR) elements and possible
      coexistence of chromogranin A (CgA), chromogranin B (CgB) and secretogranin II
      (SgII) were immunohistochemically studied in gut specimens of various vertebrate
      species. In fish, HA-IR cells were distributed mainly within the gastric and
      duodenal mucosa, and nerve fibres in the gastric myenteric plexus. Only the
      gastric HA-IR cells co-stored SgII. In frog specimens, HA-IR endocrine cells and
      nerve fibres were found in the distal stomach wall, but SgII coexisted only in
      the nerve fibres. In lizard, HA-IR endocrine cells were widely distributed from
      the oesophagus to the small intestine, but only those in the stomach co-stored
      CgA, CgB and SgII. In chick, HA-IR cells were found in the proventriculus and
      almost all co-stored all three proteins. In rat, HA-IR cells were accumulated in
      the oxyntic mucosa and all of them constantly immunostained for CgA only.

PMID- 11322318
TI  - Effect of clofibrate on the peroxisomes of the intestine of the rat during foetal
      development.
AB  - The aim of the present work was to study the action of clofibrate, known as
      peroxisomal proliferator, on the intestinal peroxisomes in the foetus of treated
      pregnant females. The Novikoff technique (catalase activity detection) shows an
      increase in the number and size of intestinal peroxisomes in the treated females
      and in the foetus. Significant differences were observed between enterocyte
      peroxisomal enzymatic activities (catalase and PBE: peroxisomal bifunctional
      enzyme) in treated and control females on the one hand, and in the foetus of
      treated and control mothers on the other. The ultrastructural immunocytochemical
      study of the PPAR (peroxisome proliferator activated receptor) shows labelling of
      the enterocyte nucleus and mitochondria by the gold particles.

PMID- 11322319
TI  - Hepatic microcirculation as a morpho-functional basis for the metabolic zonation
      in normal and pathological rat liver.
AB  - The hepatic microcirculation is well known as a fundamental component of the
      liver structure, deeply involved in the zonal organization of the acinar
      structure. In cirrhosis, the microvascular tree shows dramatic changes that would
      heavily influence the development of the disease. When the cirrhosis becomes
      evident the result is a progressive organ failure, also in presence of only
      moderately decreased hepatocyte volume. The aim of this research was to compare
      the role of microcirculation of the hepatic zonation in normal and cirrhotic
      livers. Cirrhosis was experimentally induced in 36 rats following a controlled
      intragastric CCl4 administration. Cirrhotic and control normal livers were
      processed for routine light microscopy, histoenzimology, and scanning electron
      microscopy vascular corrosion cast. Control livers showed normal hepatic
      structure and microvascularization; enzymatic activities were constantly and
      normally distributed. In CCl4-treated animals LM showed a characteristic
      micronodular cirrhosis in all livers. Vascular corrosion casts under the scanning
      electron microscope displayed a progressive reduction of the distance between pre
      and post-sinusoidal vessels and the presence of newly formed perinodular plexus.
      The histoenzymatic analysis demonstrated the loss of zonation in the cirrhotic
      parenchyma. Moreover, the sinusoid/hepatocyte ratio was significantly reduced,
      because of the presence of two or more hepatocyte thick laminae during the
      scarring development. The altered microcirculation in cirrhosis also changed the
      normal acinous metabolic gradient. The histoenzymatic study revealed a zonal
      rearrangement of the cirrhotic liver metabolic activity, that leads to a
      progressive hepatic failure. These data confirm the fundamental importance of the
      normal relationship between the hepatocyte laminae and the sinusoids for the
      preservation of a normal zonation which represents the basis for a normal liver
      function.

PMID- 11322320
TI  - Study of the elastic fibres' framework of the rat lung.
AB  - A combination of intravascular resin injection and formic acid incubation was
      used to study the three-dimensional organization of the elastic fibres of the
      adult rat lung by scanning electron microscopy (SEM). After SEM observations, the
      same samples were further processed for transmission electron microscopy (TEM) in
      order to confirm the presence of the elastic fibres and to complement some
      aspects of its surface morphology observed under the SEM. Complementary studies
      by light microscopy (LM) and TEM using specific histochemical methods for the
      elastic fibres were also performed. The SEM study clearly demonstrated that the
      cast of the microvasculature acted as a scaffold to preserve the in vivo
      arrangement of the easily collapsible elastic tissue. The methodology used
      allowed the observation of a fine framework of elastic fibres representing
      remnants of the alveolar walls in close association with the capillaries
      interwoven with the network of elastin. Each thick elastic fibre was composed of
      a bundle of thin fibres. Some of these thin fibres separated from the main fibre,
      join other fibres, giving the appearance of an anastomosing net. The interwoven
      network of elastin and its proximity with the capillaries suggests that the
      distensibility of the alveolar wall should contribute to the subtle rhythmical
      change of the alveolar microcirculation at each respiratory movement. On the sub
      pleural region of the lung, the elastic fibres were observed forming a continuous
      and fine mesh network. The elastic fibres linking the walls of the intrapulmonary
      conducting airways, the vessels wall and the alveolar and sub-pleural elastic
      network establish an interrelated and interlaced continuous framework, certainly
      with great physiological implications to the overall process of the mechanics of
      the lung respiratory function. The methodology applied was a useful tool in order
      to study the spatial organization of the pulmonary elastic fibres, its branching
      and close relation with the other lung structures.

PMID- 11322322
TI  - Electron microscopic studies of ciliogenesis and ciliary abnormalities in human
      oviduct epithelium.
AB  - Ciliogenesis in human oviduct epithelium was studied with transmission and
      scanning electron microscopes. Both centriolar and acentriolar pathways were
      involved in duplication of centrioles. The plasma membrane surrounding the base
      of new cilia invaginated toward the distal end of the basal body during formation
      of transitional fibers. Fibrous granules were involved in development of striated
      rootlets in addition to formation of centrioles. The tips of rootlets elongated
      in fibrils with a banding pattern different from that of usual rootlets; further
      the fibrils' tips were laterally connected to cell organelles (mostly
      mitochondria). Ciliogenic cells in early stages contained secretory granule-like
      vesicles, suggesting that ciliogenic cells are differentiated from secretory
      cells. The ordinary course of ciliogenesis was disturbed in some ciliogenic
      cells, resulting in formation of various ciliary abnormalities. Intracytoplasmic
      ciliated cysts, cilia within periciliary sheaths, and intracytoplasmic axonemes
      were formed due to disturbance of migration of duplicated centrioles. Swollen
      cilia and some compound cilia were developed during ciliary elongation.

PMID- 11322321
TI  - Involvement of interstitial cells in endotoxin-induced acute lung injury. A
      histochemical and electron microscopical study.
AB  - Instillation of endotoxin into the rat trachea causes a disease representative of
      the lung response to several types of inflammatory injury and--in part--of human
      acute respiratory distress syndrome. Oxidizing radicals, including nitric oxide
      (NO), may be suspected to play some role in these conditions. The participation
      of leukocytes to tissue damage in these conditions has been reported, but the
      behaviour of lung interstitial cells in unknown. In this study, we have
      investigated on possible sources of NO and the response of lung interstitial
      cells during endotoxin-induced experimental lung injury. Rats were subjected to
      intratracheal instillation of endotoxin (5 mg/kg body weight) and sacrificed
      after 12, 24 and 48 h; animals treated with saline or sham-operated were used as
      controls. Analyses included conventional light microscopy, histochemical
      detection of NADPH-diaphorase (which co-localizes with NO synthase) and electron
      microscopy. Lung infiltrates appeared after 12 h and became progressively more
      severe up to 48 h. NADPH-diaphorase positive cells appeared in the septa after 24
      h and became more numerous after 48 h; their nuclei were smooth-surfaced and the
      cytoplasm often extended into projections. By electron microscopy, only
      interstitial fibroblasts had a morphology similar to that of NO synthase positive
      cells and increased in number in the septa at the same time. These cells formed
      incomplete cuffs around blood capillaries and became large and rich in
      endoplasmic reticulum, as compared to those of the controls. These data suggest
      that hypertrophic fibroblastic interstitial cells can concur to maintain
      capillaries dilated (by NO secretion) and impair respiratory gas diffusion (by
      intervening between capillaries and pneumocytes), during experimental acute
      respiratory distress in the rat.

PMID- 11322323
TI  - Microvasculature in the mouse ovarian follicle demonstrated by a lectin
      angiography method.
AB  - A lectin angiography method was applied to identify ovarian vasculature in 32-34
      days old mice treated with gonadotropins. Blood was washed out by perfusion until
      the inferior vena cava became translucent. Horseradish-peroxidase (HRP)
      conjugated Concanavalin A (Con A) solution (10-15 ml) was perfused into the
      systemic circulation via the left ventricle at the rate of 2-3 ml/min. The
      animals were left for a 30 min reaction interval. The lumina of the blood vessels
      were flushed with 5-10 ml of phosphate buffered saline (pH 7.4). The ovaries were
      excised and fixed by immersion in 4% paraformaldehyde and sectioned serially at
      thickness of 100, 200 or 400 microm using a Microslicer. The binding of HRP
      conjugated-Con A to endothelial cells was visualized by using 3,3'
      diaminobenzidine-4 HCl (DAB-4 HCl) reaction. By examining various sections the
      three-dimensional architecture of the vascular networks of the preovulatory
      Graafian follicles and corpora lutea can be established. Capillary networks of
      preovulatory Graafian follicles were identified in sections of ovaries removed 11
      h after hCG injection. Then, capillary networks of the Graafian follicles
      increased due to the hypertrophic growth of the theca interna and extension of
      capillary branches into the follicles. Well-developed capillary networks of
      corpora lutea were found in ovaries removed 24 h after hCG injection. For these
      observations the 200 microm-sections were the most useful. The present modified
      lectin angiography is a useful method for visualizing the microvasculature of
      mouse ovaries.

PMID- 11322324
TI  - Changes of ovarian microvasculature in hCG stimulated rabbits. A scanning
      electron microscopic study of corrosion casts.
AB  - The microvasculature of the ovarian cortex was studied by means of scanning
      electron microscopy of vascular corrosion casts in estrous and hCG stimulated
      rabbits in order to establish a better understanding of the structural as well as
      functional vascular changes which accompany the evolution of the luteofollicular
      complex. According to the various shape and size seven different morphological
      types of vascular plexuses corresponding respectively to antral follicles (Types
      1-2), atretic follicles (Types 3-4), periovulatory follicles (Type 5), growing
      pseudopregnant corpora lutea (Type 6) and regressing pseudopregnant corpora lutea
      (Type 7) were identified. Growing to mature cycling type follicles (Types 1-2)
      showed a gradual enlargement and proliferation of the theca capillaries. These
      changes, associated with capillary hyper-permeabilization were observed in
      ovulatory and post-ovulatory follicles (Types 5), after hCG stimulation. The
      corpus luteum formation (Types 6) was accompanied by additional capillary
      dilatation, diffuse angiogenetic sprouts and organization of a more conspicuous
      venous drainage. The regression of the corpus luteum (Type 7) was characterized
      by the appearance of avascular areas within the glandular tissue and by
      regression of vascular dilatation. The atretic follicle (Types 3-4) wall showed
      large interruptions (avascular areas) and focal invasion of the central cavity by
      newly formed capillaries randomly arranged. The hCG stimulation did not affect
      consistently the atretic follicle microvasculature. The present observation shows
      that both thecal capillary vasodilatation and angiogenetic processes support the
      gradual increase of ovarian blood flow during follicle growth and corpora lutea
      formation and that microvascular changes of atretic follicles are possibly
      related to a type of inflammatory reaction since they seem to be a consequence
      rather than a primary cause of atresia.

PMID- 11322325
TI  - Ultrastructural and confocal laser scanning microscopical aspects of apoptosis in
      cultured human neuroblastoma SH-SY5Y cells.
AB  - Programmed cell death or apoptosis is a physiological process that plays an
      important role during development and maintains tissue homeostasis during adult
      life. In pathological conditions, such as cancer, apoptosis may be the mechanism
      by which cancer proliferation is hampered. Many antineoplastic drugs act by
      inducing apoptosis. SH-SY5Y human neuroblastoma cells undergo apoptosis when
      exposed to cisplatin, an effective antineoplastic drug. The occurrence of cell
      death by the apoptotic process is evidenced by the typical electrophoretic
      laddering of DNA, which begins 24 h after cisplatin exposure and becomes even
      more apparent at 3-4 days after exposure. Concomitantly, ultrastructural changes
      of the nucleus and nucleolar organization occur, followed by nuclear membrane
      disruption and, finally, by cytoplasm degeneration. These last two aspects are
      present in cultured cells detached from the substrate and predominate in long
      term cultures after drug exposure. Confocal laser scanning microscopy (CLSM) of
      orange-acridine stained nuclei also clearly demonstrates the fragmentation of the
      chromatin into 3-5 domains. The CLSM, therefore can clearly demonstrate the
      occurrence of apoptosis in a much simpler, but equally accurate way than electron
      microscopy.

PMID- 11322326
TI  - Hyaluronic acid and proteoglycan accumulation in the cumulus oophorus matrix.
AB  - A factor produced by the oocytes induces in vitro FSH-treated cumulus and mural
      granulosa cells to synthesize hyaluronic acid. In the present study we examined
      hyaluronic acid synthesis by the two cell populations in vivo. After injection of
      hCG into PMSG-primed immature mice, cumulus and mural granulosa cells adjacent to
      the antrum synthesized a large amount of such glycosaminoglycan, while the
      outermost layers layers of mural granulosa cells did not. The results suggest
      that in vivo differences in hyaluronic acid synthesis between follicle cell
      subpopulations depend on a diffusion gradient of the oocyte factor. We also
      identified a proteoglycan species synthesized by cumulus cells which may
      contribute to hyaluronic acid organization in the intercellular spaces.

PMID- 11322327
TI  - Steroidogenic activity and ultrastructural observation of atretic follicles in
      the cycling hamster ovary.
AB  - In mature hamster ovaries, many follicles undergo atresia and this atretic change
      occurs in any estrous day. In this study, the localization of enzymes involved in
      estrogen biosynthesis, Bromodeoxyuridine (BrdU) incorporation, and Proliferating
      Cell Nuclear Antigen (PCNA) were immunohistochemically examined in the atretic
      follicles always provided with an atrum variable in size. Moreover, the granulosa
      cells from the atretic follicle in various but parallel stages of development
      were examined by scanning and transmission electron microscopes. Very early
      morphological signs of atresia in these follicles was the pyknotic change of a
      few granulosa cells lining the antral cavity. In this kind of follicles, the
      number of BrdU incorporating granulosa cell was decreased and the
      immunoreactivity of PCNA and aromatase was gradually decreased. Even in the early
      stage of atresia, some granulosa cells showed a remarkable morphological change
      characteristic of apoptosis as revealed by scanning and transmission electron
      microscopy.

PMID- 11322329
TI  - The foetal macrophage of the human placenta.

PMID- 11322328
TI  - The collagen fibrils arrangement in the Wharton's jelly of full-term human
      umbilical cord.
AB  - In the present study, a cell maceration/scanning electron microscopy method is
      employed in order to reveal the three-dimensional organization of the collagen
      fibrils in the Wharton's jelly of the human umbilical cord at term. By this
      method the jelly appears as a three-dimensional network of collagen fibrils that
      runs continuously from the amniotic membrane to the umbilical vessels. A diverse
      architecture of the collagen fibrillar network in the inner and outer region of
      the cord is observed suggesting an anatomical as well as a functional
      compartmentalization. In fact, the network is soft in the inner part and it is
      characterized by canalicular structures whereas in the outer region the collagen
      is dense and the network is characteristically composed by a sponge-like system
      of cavernous spaces. It is suggested that these cavities might store the ground
      substance and allow its diffusion during twisting or compression of the cord.
      Furthermore they may facilitate the flow of metabolites throughout the jelly from
      and to the umbilical vessels and the amniotic cavity.

PMID- 11322330
TI  - Human male genitourinary tract: an immunohistochemical study of secretory IgA.
AB  - Male human genitourinary tract was treated for the immunohistochemical
      demonstration of secretory IgA (sIgA) in order to verify its own possible
      antimicrobial properties. An intense immunoreactivity for sIgA was observed in
      the apical cells of the urethral and vesical epithelia. The ureteric epithelium,
      at the luminal surface, showed discontinuous areas of less dense or completely
      absent reaction product. A less intense immunoreactivity in the pelvic apical
      epithelial cells was found; an intensely positive immunoreaction for sIgA in the
      epithelial cells of prostate and urethral glands was also observed. The results
      suggest that a local immune response sIgA-mediated is present in the lower male
      urogenital tract.

PMID- 11322331
TI  - Alfa-inhibin and transferrin in human fetal testis.
AB  - Aim of this research was to investigate the immunohistochemical localization of
      alfa-inhibin and transferrin in the human fetal testis. In addition, an attempt
      was made to identify the Sertoli cells in primary cell cultures of fetal testes
      by the demonstration of the mRNA for transferrin and the presence of the FSH
      receptor. 15 fetal testes (8-12 weeks) were utilized. The results of this study
      show: 1. In sections, immunoreactivity for alfa-inhibin was present in the
      interstitial cells, whereas transferrin was localized in Sertoli cells; 2. After
      20 days of primary culture: a) the percentage of immunoreactive cells for both
      the substances was about 15%; b) the presence of FSH receptor and the expression
      of transferrin mRNA were observed in 12-15% of cells. These findings suggest: 1.
      alfa-inhibin and transferrin are present in the human fetal testis; 2. the
      expression of transferrin mRNA and the presence of the FSH receptor permit the
      identification of the Sertoli cells in primary cultures of fetal testes (8-12
      weeks).

PMID- 11322332
TI  - Ultrastructure of human Leydig cells at early gonadal embryogenesis.
AB  - The ultrastructure of human Leydig cells at different stages of the testicular
      prenatal development is described by means of transmission and scanning electron
      microscopy. Between 5 and 7 weeks of gestation (w.g.) the interstitial tissue of
      the gonad is filled with small undifferentiated mesenchymal cells, migrating
      primordial germ cells and blood vessels. When the embryo is 7 to 8 weeks-old
      Leydig cells (LC) appear in basically two morphological patterns, light and dark
      cells. Their most significative feature is the development of the smooth
      endoplasmic reticulum (SER) as a dense tubulo-vesicular network and the presence
      of numerous pleomorphic mitochondria with mainly lamellar cristae. At 14 and 16
      w.g. the testicular interstitium reaches the maximum development; the cytoplasm
      of the LC shows a widespread network of anastomosing tubules of the SER and
      mitochondria with tubular cristae. Fetal LC show a partial cell coat, lack the
      crystals of Reinke, have few lipid droplets and show no signs of massive cell
      degeneration, at least until 16 w.g. These ultrastructural modifications in fetal
      LC are in accordance with the changes in both steroidogenic activity and hCG
      levels reported by the literature to occur at this stage of development.
      Junctional complexes were often observed among LC from 7 to 8 w.g. onwards.

PMID- 11322333
TI  - Morphological studies on the origin of adult-type Leydig cells in rat testis.
AB  - The differentiation of adult-type Leydig cells (ATLC) in rat testis was studied
      with the help of electron microscopy and a combined technique of autoradiography
      and enzymehistochemistry. Male Wistar rats on each alternative day from postnatal
      day (pnd) 9 to 25 were perfused in situ, and the testicular sections were
      observed by electron microscopy. The cytoplasm of the ATLC contained smooth
      endoplasmic reticulum, mitochondria, a few small lipid droplets and a large well
      developed Golgi apparatus. In addition to typical fibroblasts/fibrocytes, a group
      of fibroblast-like cells was observed in the peritubular and perivascular spaces
      of the interstitial tissue. These cells, containing smooth endoplasmic reticulum
      and a large number of mitochondria with tubular-type cristae, were named as
      intermediate-type cells. In the autoradiographic experiments the 3-H-thymidine
      and 14-C-thymidine uptake behaviour of fetal-type Leydig cells, ATLC,
      intermediate-type cells and myoid cells was studied from 1 till 25 pnd. The
      intermediate-type cell, observed predominantly between pnd 9 to 21, showed the
      highest labelling index. The absolute number of fibroblasts/fibrocytes showed a
      peak on pnd 13 and decreased gradually with age. The duration of DNA synthesis
      phase ranged for interstitial fibroblasts: 7.9 h, for intermediate-type cell 10.4
      h, for ATLC 17.4 h. The results lead to the conclusion that ATLC most probably
      originate to a large extent from the peritubular and to a lesser extent from
      perivascular fibroblast-like cells of the interstitial tissue.

PMID- 11322335
TI  - Membrane-bound guanylate cyclase as the receptor of natriuretic peptides. A
      minireview.
AB  - A minireview is presented on the ultracytochemical localization of membrane-bound
      guanylate cyclase (GC) in various tissues and in cultured cells after activation
      with three natriuretic peptides, the atrial natriuretic factor (ANF), the brain
      natriuretic peptide (BNP), and the C-type natriuretic peptide (CNP). GC, two
      subtypes of which have been recently identified, is the receptor for these
      peptides. The GC isoforms are differently stimulated by ANF, BNP and CNP. Under
      our experimental conditions, the natriuretic peptides were strong activators of
      GC since samples incubated without natriuretic peptides do not reveal any cyclase
      activity. The natriuretic peptide-stimulated GC activity was studied in rat
      kidney, lung, adrenal gland and neurohypophysis, in rabbit platelets, in lamb
      olfactory mucosa, and in rat C6 glioma cells. On the basis of the subcellular GC
      localization some additional functions of peptides are hypothesized.

PMID- 11322334
TI  - Expression of neurotrophin receptors in the developing and adult testis.
AB  - Nerve growth factor (NGF) and the other members of the family of neurotrophic
      factors (the neurotrophin) are essential for neuronal development and
      differentiation. Neurotrophins interact with two types of cell surface receptors:
      a low-affinity receptor (p75 NGF-R) and a high-affinity tyrosine kinase receptor
      belonging to the trk proto-oncogene family, both expressed in the nervous system
      and in certain non-neuronal tissues. Recently, NGF immunoreactivity and mRNA have
      been detected in the testis of the adult mouse, rat and human. In the present
      report we demonstrate the expression of p75 NGF-R during early gonadal
      development, by mesenchymal cells of the embryonic mouse and rat testis. In the
      embryonic testis p75 NGF-R-positive cells are spread through the interstitial
      compartment; during postnatal development they become organized in a cellular
      layer that surrounds differentiating myoid cells of the seminiferous tubule. Our
      results also show the expression in the peripuberal and adult mouse and rat
      testis, of an abundant and shorter transcript of 3.2 kb that cross-hybridizes to
      the receptor mRNA (3.7 kb). This new mRNA species, which appears at the beginning
      of spermatogenesis, is expressed by pachytene spermatocytes and round spermatids.

PMID- 11322336
TI  - TNF-alpha induces surface modifications in mouse Sertoli cells:
      physiopathological implications.
AB  - The expression of the adhesion molecules ICAM-1 and VCAM-1 has been measured in
      mouse Sertoli cells cultured in vitro. Cytometric analysis revealed that, in
      basal conditions, low levels of ICAM-1 and VCAM-1 were present on the surface of
      the cells, whereas treatment with TNF-alpha induced an increase in their
      expression. Binding experiments using both 51Cr-labelled lymphocytes, for
      quantitative analysis, and scanning electron microscopy demonstrated that
      increased expression of ICAM-1 and VCAM-1 on the surface of Sertoli cells,
      induced by TNF-alpha, determines an augmented adhesion between the two cell
      types. These results suggest the presence of a specific mechanism of interaction
      between Sertoli and immune-competent cells, possibly involved in the control of
      the immune response in the testis following an inflammatory reaction in situ.
      Such mechanism is of interest for the understanding of auto-immune pathologies of
      the testis and, if confirmed in humans, it could be involved in the sexual
      transmission of HIV infection.

PMID- 11322337
TI  - Immunohistochemical localization of neurotrophin receptor proteins in human skin.
AB  - The target organs of neurotrophin-dependent sympathetic and sensory neurons,
      including the skin, synthesize and release neurotrophins, primarily NGF.
      Neurotrophins undergo retrograde axonal transport, and exert specific function in
      the perikarya of the responsive neurons. Moreover, evidence exists for an
      autocrine and/or paracrine function of neurotrophins in the skin. This study
      analyses the immunohistochemical localization of low (gp75) and high-affinity
      (gp140 trkA, gp145trkB and gp145trkC) neurotrophin receptor proteins in the human
      glabrous skin. We consider that the expression of neurotrophin receptors may be
      indicative of neurotrophin activity. Specific gp75 and gp140trkA-like
      immunoreactivity (IR) were observed highly co-localized in (1) epidermis,
      primarily in the basal keratinocytes; 2) sweat glands; (3) blood vessel walls,
      mainly in the muscular layer; (4) Schwann and perineurial cells of nerve trunks;
      (5) periaxonic cells forming sensory nerve formations (Meissner's and Pacini's
      corpuscles); (6) large axons of nerve bundles and of sensory corpuscles;
      gp145trkB-like and gp145trkC-like were found labelling nerve fibers and sensory
      nerve formations, as well as blood vessels and sweat glands, but not epidermic
      cells. The results suggest that, in addition to the well known neurotrophic
      functions, neurotrophins may also regulate unknown functions in non-nervous
      cutaneous cells, which are targets for neurotrophin-dependent sympathetic and
      sensory neurons.

PMID- 11322338
TI  - Ultrastructure of lamellar complexes in glomerular Krause spherical corpuscles.
AB  - The authors compared the ultrastructure of lamellar complexes in the penis skin
      of the green monkey and in the woman's clitoris skin. In the green monkey the
      lamellar complexes consist of a maximum of 5 lamellae of Schwann cells, their
      greatest width is about 4.5 microm. The interlamellar spaces are filled with fine
      filamentous material. In the woman the lamellar complexes consist of a maximum of
      7 lamellae, the interlamellar spaces are narrower than in the first case and
      filled with collagenous fibrils. Their maximum width is about 6.5 microm. The
      findings thus support the view that the lamellar complexes of glomerular
      corpuscles are morphologically and functionally similar to other simple lamellar
      corpuscles. The glomerular corpuscles contain also some non myelinated thin nerve
      fibers. Therefore for these corpuscles an additional (unclear) function can be
      considered.

PMID- 11322339
TI  - Initial lymph vessels of the skin and elastic fibres form an integral
      morphofunctional structure.
AB  - Little has been published on the histochemical and cytochemical properties of
      anchoring filaments of the initial lymph vessels. Previous research suggests that
      the microfibrils of the anchoring filaments have ultrastructural, histochemical
      and cytochemical characteristics similar to those of the microfibrils associated
      with the elastic fibres. With the aim of further investigating the histological
      identity of anchoring filaments, we performed an immunohistochemical study in
      human skin lymphatics, using the antibody HB8, specific for elastic fibre
      microfibrils. There is now a body of evidence suggesting a new concept in the
      framework of the lymphatic system. It unifies the initial lymph vessels, the
      anchoring filaments and the satellite elastic fibres in a single and integral
      entity.

PMID- 11322340
TI  - Morphometry in anatomy: image analysis on fine structure and histochemical
      reactions with special reference to radioautography.
AB  - Anatomy now has a step to transfer from qualitative science to quantitative
      science. The methods of anatomical investigation employ optical instruments.
      Anatomy initially described qualitative features of the structure of the body,
      but now it turns to transfer to new fields measuring the number, size, length,
      area and volume of not only, structure but also the histochemical components of
      the structure with quantitative analysis. In order to quantify histochemical
      reactions in various organs, light and electron microscopic radioautograms were
      prepared from the liver, pancreas, intestines and kidney which were labeled with
      3H-thymidine, 3H-uridine, 3H-leucine, 3H-glucosamine and 3H-glycerol, fixed in
      glutaraldehyde and osmium tetroxide, embedded in Epoxy resin, sectioned either
      thick or thin, coated with either Konica NR-M2 or -H2 radioautographic emulsions,
      exposed, developed, stained for either light or electron microscopic
      radioautographs. The radioautographs were observed with Olympus Vanox AHB-LB or
      Nikon Optiphot-2 light microscopes or Hitachi H-700, JEOL JEM-4000EX electron
      microscopes at 200 and 400 kV. The radioautograms were analysed with various
      image and analysed such as PPA-250, MOP, Digigramer-G, IBAS-II, Quadra 900, Luzex
      300 to count the number of silver grains and to measure the size and number of
      structures. Some electron microscopic radioautographs were analysed in analytical
      electron microscopes, combined with Hitachi H-700 Horiba EMAX-1800E, JEOL JEM
      200CX Kevex 7000-77, and JEOL JEM-4000EX Tracor-Northern TN-5400 to quantify
      silver grain contents. The results demonstrated that correct data can be obtained
      by controlling both full-automatic and semi-automatic image analysers by
      operating them manually.

PMID- 11322341
TI  - A method for histomorphometric characterization of a peri-implantar new formed
      tissue to biomaterials.
AB  - The spatial distribution and concentration of distinct cellular elements are of
      interest in the evaluation of the biological reaction to implant materials, the
      so called biomaterials. We present a method, based on a computer assisted cell
      counting program, developed to quantify the soft tissue reaction to implanted
      material. Five pseudomembranes formed around silicone skin expanders were
      studied; they were subjected to histological immunohistochemical and
      histomorphometrical investigation. This quantitative approach overcomes weakness
      due to the subjectivity of the observers and offers new possibilities when
      assaying the local tissue compatibility; moreover, it shows a good applicability
      to a wide variety of implant materials.

PMID- 11322342
TI  - A comparision between rapid Golgi and Golgi-Cox impregnation methods for 3-D
      reconstruction of neurons at the confocal scanning laser microscope.
AB  - We utilized two widely used impregnation methods, the silver "rapid Golgi" and
      the mercuric Golgi-Cox methods, for three-dimensional (3-D) reconstruction of
      neurons at the confocal scanning laser microscope (CSLM), to determine which of
      them was more suitable for this application. The Golgi-Cox method is the most
      consistent arid the cleanest procedure with respect to the "rapid Golgi" one
      which always produces samples with scattered reflective granules that interfere
      with the image formation at the CSLM. The interneuronal tissue in the case of
      Golgi-Cox impregnated specimens (i.e. the non-impregnated tissue among
      impregnated neurons) contributes less to the decrease of reflected light during z
      sectioning than in the case of "rapid Golgi" impregnation, but the mercury
      impregnated samples reflect less than the silver impregnated ones. Owing to the
      necessity during deep z-scanning to adjust the sensitivity of the CLSM detector
      the acquisition of images from the deeper planes of the sample may be difficult.
      In our opinion the "sandwich" mounting of the specimen between two coverslips is
      indispensable in order to make it possible to scan it from both sides and, thus
      reduce the penetration in the sample and the consequent distortion of the image.
      Neither of the impregnation methods used is completely suitable for CLSM
      observations due both to their intrinsic limitations and to those imposed by the
      sample thickness.

PMID- 11322343
TI  - Involvement of the cytoskeleton in regulation of collagen synthesis and
      secretion.
AB  - 11-day chick embryo skin fibroblasts administered in vitro with colchicine or
      cytochalasin B, have been investigated for collagen synthesis and secretion. The
      cytoskeleton, examined by confocal laser scanning immunofluorescence microscope,
      exibited in colchicine treated cells a clear loss of microtubules, in
      cytochalasin B treated cells a diffuse staining and patches of intracellular
      fluorescence caused by actin disassembly. Cytochalasin B treatment decreased
      endocellular type I collagen synthesis and the total uptake of 3H-proline, while
      enhanced collagen secretion. Colchicine did not interfere with the collagen
      secretion and the label uptake, whereas it increased endocellular collagen
      synthesis. In addition, both drugs induced an increase of the alpha2:alpha1 ratio
      of collagen chains. The results obtained suggest that the cytoskeleton controls
      not only the morphological organization of cell components, but also the
      organization of biochemical processes.

PMID- 11322344
TI  - Brown adipocyte precursor cells: a morphological study.
AB  - The origin of brown adipocyte precursor cells is to date unknown. Some authors
      believe they arise from vascular cells, others from interstitial cells. The
      purpose of the present ultrastructural study was to find markers in rat fetal and
      perinatal adipose tissue that can be used to identify brown adipose precursor
      cells. The study was carried out on the interscapular brown adipose tissue of
      fetal (fetuses of 19 and 21 days) and perinatal rats (pups of 4 and 12 hours and
      of 1, 3, 5, 7, 9, 11, 13, and 15 days). The analysis focused on stem cells and
      showed the characteristic presence of typical mitochondria which make their
      identification as brown adipocyte precursor cells inequivocal. These cells were
      frequently observed in a pericytic position. Also some endothelial cells were
      characterised by typical mitochondria and abundant glycogen. These data seem to
      support the hypothesis that brown adipocytes originate from vascular cells.

PMID- 11322345
TI  - Tissue culture of adult human osteoblasts isolated from jaw bones.
AB  - Shreds of biopsied adult human jaw bones were divided into four groups that were
      each incubated together with borosilicate glass chips in one of four variants of
      DMEM expansion medium (i.e., with a high or low calcium complement and with or
      without sodium ascorbate added). The outgrown bone cells were propagated in
      secondary cultures kept in the same DMEM expansion medium variants prior to being
      transferred to a beta-glycerophosphate-enriched high-Ca2+ and ascorbate
      containing DMEM mineralisation medium. In this latter medium the proliferation
      rates and the simultaneous expression of alkaline phosphatase by the four
      distinct groups of osteoblasts were assessed during 7 days of staying in vitro
      via biochemical methods. Human osteoblasts previously expanded in high-Ca2+
      ascorbate-added DMEM medium were found to initially express a quite high alkaline
      phosphatase activity that subsequently declined, while their proliferative
      activity remained rather low. Conversely, osteoblasts formerly expanded in low
      Ca2+ ascorbate-devoid DMEM medium exhibited minimal levels of alkaline
      phosphatase activity while simultaneously maximally proliferating in the
      mineralisation medium. Moreover, a mixture (1:1 v/v) of the DMEM mineralisation
      medium with Ham's medium (in which the aminoacid proline abounds) was found to
      accelerate, in comparison to DMEM alone, the intracellular type I procollagen
      synthesis, the extracellular assembly of type I collagen fibrils, and the
      calcification of the extracellular matrix by the human osteoblasts. Hence, the
      presence or absence of calcium and/or ascorbate in the expansion medium and of
      proline in mineralisation medium can significantly modulate the progression of
      human jaw bone cells from an undifferentiated highly proliferating condition to
      the mature osteoblastic phenotype.

PMID- 11322346
TI  - Collagen texture and osteocyte distribution in lamellar bone.
AB  - A comparative scanning and transmission electron microscopy study was carried out
      on collagen fiber texture and osteocyte lacunae distribution in human lamellar
      bone. The results show that bony lamellae are not made up of parallel-arranged
      collagen fibers, as classically maintained. They are instead made up of highly
      interlaced fibers, and the lamellation appears to be due to the alternation of
      collagen-rich and collagen-poor layers, namely of dense and loose lamellae. The
      present study additionally shows that osteocyte lacunae are only located inside
      loose lamellae. Such structural organization of lamellar bone is briefly
      discussed in terms of bone biomechanics and osteogenesis.

PMID- 11322347
TI  - Heinrich Wieland--Nobel Prize in Chemistry.

PMID- 11322348
TI  - Medical management of overactive bladder.

PMID- 11322349
TI  - Resolution of platelet-rich thrombi in essential thrombocythemia: mechanisms,
      risks, and benefits of antiplatelet therapy.

PMID- 11322351
TI  - Safety of electrical cardioversion in patients with previous embolic events.
AB  - OBJECTIVE: To assess thromboembolic complications in cardioversions in patients
      with atrial fibrillation or flutter and a previous embolic event. PATIENTS AND
      METHODS: The study population consisted of 104 patients with previous embolic
      events who underwent 128 electrical cardioversions for termination of atrial
      fibrillation or flutter. The primary outcome measure was successful
      cardioversion. RESULTS: Anticoagulants were administered in 118 procedures (92%).
      Cardioversion was successful in 108 (84%) of the 128 procedures. Only 1 embolic
      event occurred within 30 days after cardioversion (incidence, 0.9% of successful
      procedures; 95 % confidence interval, 0.02%-5.3%). The single embolic event was a
      transient neurologic deficit occurring 22 days after cardioversion in a patient
      with previous atrial fibrillation. This patient had a sub-therapeutic level of
      anticoagulation. Transesophageal echocardiography revealed no spontaneous echo
      contrast or thrombi before the procedure. No thromboembolism was noted in
      patients who had therapeutic anticoagulation or in those with failed
      cardioversion. CONCLUSION: Patients with previous embolism are not at additional
      risk of thromboembolic complications after cardioversion if anticoagulation is
      adequate.

PMID- 11322350
TI  - Prospective randomized controlled trial of extended-release oxybutynin chloride
      and tolterodine tartrate in the treatment of overactive bladder: results of the
      OBJECT Study.
AB  - OBJECTIVE: To compare the efficacy and tolerability of extended-release
      oxybutynin chloride and tolterodine tartrate at 12 weeks in participants with
      overactive bladder. SUBJECTS AND METHODS: The OBJECT (Overactive Bladder: Judging
      Effective Control and Treatment) study was a prospective, randomized, double
      blind, parallel-group study conducted between March and October 2000 at 37 US
      study sites. Participants who had between 7 and 50 episodes of urge incontinence
      per week and 10 or more voids in 24 hours received extended-release oxybutynin,
      10 mg/d, or tolterodine, 2 mg twice daily. The outcome measures were the number
      of episodes of urge incontinence, total incontinence, and micturition frequency
      at 12 weeks adjusted for baseline. RESULTS: A total of 315 women and 63 men were
      randomized and treated, and 332 participants (276 women, 56 men) completed the
      study. At the end of the study, extended-release oxybutynin was significantly
      more effective than tolterodine in each of the main outcome measures: weekly urge
      incontinence (P=.03), total incontinence (P=.02), and micturition frequency
      episodes (P=.02) adjusted for baseline. Both drugs improved symptoms of
      overactive bladder significantly from baseline to the end of the study as
      assessed by the 3 main outcome measures (P<.001). Dry mouth, the most common
      adverse event, was reported by 28.1% and 33.2% of participants taking extended
      release oxybutynin and tolterodine, respectively (P=.32). Rates of central
      nervous system and other adverse events were low and similar in both groups.
      CONCLUSIONS: Extended-release oxybutynin was more effective than tolterodine as
      measured by end-of-study urge incontinence, total incontinence, and micturition
      frequency episodes. Both groups had similar rates of dry mouth and other adverse
      events.

PMID- 11322352
TI  - Effectiveness of resistive heating compared with passive warming in treating
      hypothermia associated with minor trauma: a randomized trial.
AB  - OBJECTIVES: To determine the occurrence of hypothermia in patients with minor
      trauma, to test the hypotheses that resistive heating during transport is
      effective treatment for hypothermia and that this treatment reduces patients'
      thermal discomfort, pain, and fear, and to evaluate the accuracy of oral
      temperatures obtained at the scene of injury. PATIENTS AND METHODS: In December
      1999 and January 2000, 100 patients with minor trauma were randomly assigned to
      passive warming or resistive heating. All patients were covered with a carbon
      fiber resistive warming blanket and a wool blanket, but the warming blanket was
      activated only in those assigned to resistive heating. Core (tympanic membrane)
      and oral temperatures, heart rate, pain, fear, and overall satisfaction of
      patients were compared between the 2 groups on arrival at a hospital. RESULTS:
      Hypothermia was noted in 80 patients at the time of rescue. Mean initial core
      temperatures were 35.4 degrees C (95% confidence interval [CI], 35.2 degrees C -
      35.6 degrees C) in the patients who received passive warming and 35.3 degrees C
      (95% CI, 35.1 degrees C - 35.5 degrees C) in those who received resistive
      heating. From the time of rescue until arrival at the hospital, mean core
      temperature decreased 0.4 degrees C/h (95% CI, 0.3 degrees C/h - 0.5 degrees C/h)
      with passive warming, whereas it increased 0.8 degrees C/h (95% CI, 0.7 degrees
      C/h - 0.9 degrees C/h) with resistive heating. Oral and tympanic membrane
      temperatures were similar. Mean heart rate decreased 23 beats/min in those
      assigned to resistive heating but remained unchanged in those assigned to passive
      warming. Patients in the resistive heating group felt warmer, had less pain and
      anxiety, and overall were more satisfied with their care. CONCLUSIONS: Oral
      temperatures are sufficiently accurate for field use. Hypothermia is common even
      in persons with minor trauma. Resistive heating during transport augments thermal
      comfort, increases core temperature, reduces pain and anxiety, and improves
      overall patient satisfaction.

PMID- 11322353
TI  - The effect of changing transfusion practice on rates of perioperative stroke and
      myocardial infarction in patients undergoing carotid endarterectomy: a
      retrospective analysis of 1114 Mayo Clinic patients. Mayo Perioperative Outcomes
      Group.
AB  - OBJECTIVE: To evaluate changes in the institution's red blood cell (RBC)
      transfusion practice during the past 15 years and the influence of these changes
      on neurologic or cardiac morbidity after carotid endarterectomy. PATIENTS AND
      METHODS: Based on a retrospective analysis of the Mayo Clinic database, 1,114
      patients who underwent carotid endarterectomy were stratified into 1 of 2 groups:
      (1) 1980 to 1985 (ie, pre-human immunodeficiency virus screening, early-practice
      group [n=552]) and (2) 1990 to 1995 (ie, recent-practice group [n=562]). Data
      were compared between time periods using the chi2 test for categorical variables
      and the rank sum test for continuous variables. Logistic regression was used to
      assess the association between perioperative transfusion practice and the
      occurrence of stroke or myocardial infarction. Two-tailed P values < or = 05 were
      considered statistically significant. RESULTS: Patients in the recent-practice
      group were significantly older (mean +/- SD age, 69.6 +/- 8.7 years) vs 65.9 +/-
      8.3 years in the early-practice group (P<.001). The proportion of patients
      receiving perioperative RBC transfusion decreased dramatically from 72.9% in 1980
      1985 to 8.7% in 1990-1995 (P<.001). Additionally, the mean +/- SD number of RBC
      units transfused decreased from 1.10 +/- 1.30 U in 1980-1985 to 0.27 +/- 1.22 U
      in 1990-1995 (P<.001). Mean +/- SD discharge hemoglobin concentration decreased
      from 13.7 +/- 1.4 g/dL in 1980-1985 to 11.8 +/- 1.5 g/dL in 1990-1995 (P<.001).
      Rates of perioperative stroke and myocardial infarction did not differ between
      the 2 time periods (early-practice group vs recent-practice group: stroke, 5.1%
      vs 3.6% [P=.22]; myocardial infarction, 1.5% vs 2.3% [P=.29]). CONCLUSIONS: Our
      results suggest that elderly patients undergoing carotid endarterectomy (ie,
      individuals known to be at high risk for cerebral and cardiac ischemia) can
      tolerate modest perioperative anemia despite a considerable change in the
      institution's transfusion practice (lower "transfusion trigger," the hemoglobin
      concentration or hematocrit value below which RBC transfusion is indicated).

PMID- 11322354
TI  - Treating fibromyalgia with a brief interdisciplinary program: initial outcomes
      and predictors of response.
AB  - OBJECTIVES: To evaluate the efficacy of a brief, intense treatment program for
      fibromyalgia and to determine which patient characteristics are associated with a
      better treatment response. PATIENTS AND METHODS: Two self-report measures, the
      Fibromyalgia Impact Questionnaire (FIQ) and the Multidimensional Pain Inventory
      (MPI), were administered before patients completed treatment and 1 month after
      participating in the program. The main outcome measure was the difference in FIQ
      score and MPI scale before and after program participation. RESULTS: Of 139
      patients who met the American College of Rheumatology criteria for fibromyalgia,
      100 chose to participate in the 1 1/2-day Fibromyalgia Treatment Program at the
      Mayo Clinic, Rochester, Minn. Of these 100 patients, 74 completed the follow-up
      surveys. Patients were less affected by fibromyalgia after participation in the
      treatment program. This was demonstrated by a posttreatment improvement in the
      total FIQ score (P<.001), the MPI pain severity score (P<.001), and the MPI
      interference score (P=.01). The 1 patient characteristic found to be
      significantly associated (P<.001) with a better response to treatment was a high
      pretreatment level of impairment from fibromyalgia, as measured by the
      pretreatment FIQ score. CONCLUSIONS: A brief interdisciplinary program for
      treating fibromyalgia reduced some associated symptoms. Patients more severely
      affected by fibromyalgia may benefit most from this approach. Clinicians may
      apply these findings to develop beneficial and convenient treatment programs for
      patients with fibromyalgia.

PMID- 11322355
TI  - Adjunctive therapies in the treatment of acute coronary syndromes.
AB  - Survival after myocardial infarction has been improving steadily in recent
      decades, in part because of more effective adjunctive medical therapies. However,
      the issue of underutilization of effective medical therapies remains. Adjunctive
      therapy for acute myocardial infarction should include aspirin, beta-adrenergic
      blocking agents, angiotensin-converting enzyme inhibitors, and lipid-lowering
      agents, all of which improve survival in the treatment and secondary prevention
      of myocardial infarction. This review presents the current knowledge supporting
      the use of specific adjunctive pharmacologic agents and also discusses the
      current status of other agents that are emerging or controversial.

PMID- 11322356
TI  - Immune reconstitution after autologous hematopoietic stem cell transplantation.
AB  - Autologous hematopoietic stem cell transplantation has proved to be an effective
      treatment for certain hematologic malignancies. However, relapse rates are high
      during the first year after transplantation. These relapses are attributed to the
      failure of high-dose chemotherapy to eradicate minimal residual malignant
      disease. In allogeneic hematopoietic stem cell transplantation, the higher
      antitumor effects observed compared with those in autologous hematopoietic stem
      cell transplantation are based on the immunologically mediated graft-vs-tumor
      effect. Therefore, a better understanding of the mechanisms involved in immune
      reconstitution after hematopoietic stem cell transplantation may clarify the
      importance of various components of the recovery of the immune system as they
      pertain to eradication of residual tumor, as well as uncover possible
      interventions directed at maximizing this effect. This review focuses on immune
      reconstitution after autologous hematopoietic stem cell transplantation.
      Autologous hematopoietic stem cell transplantation is not affected by graft-vs
      host disease or immunosuppressive therapy after transplantation to control graft
      vs-host disease, providing a direct insight into the mechanisms involved in
      immune reconstitution after engraftment.

PMID- 11322358
TI  - 25-year-old man with headaches and blurred vision.

PMID- 11322357
TI  - Subclinical thyroid disease.
AB  - The term subclinical thyroid disease is used to describe asymptomatic thyroid
      abnormalities found on imaging studies or laboratory tests. Thyroid nodules not
      palpable on physical examination but detected on imaging studies performed for
      other purposes are called incidentalomas. In the absence of risk factors for
      thyroid cancer, nodules that are less than 1 cm in diameter do not require
      biopsy. Subclinical hyperthyroidism is defined as suppressed serum sensitive
      thyrotropin (TSH) and normal serum thyroxine and triiodothyronine levels. This
      condition may adversely affect the heart and the bones and should be treated,
      especially in patients older than 60 years. Subclinical hypothyroidism, defined
      as mildly elevated serum TSH and normal serum thyroxine levels, is the most
      common thyroid dysfunction. In patients with subclinical hypothyroidism,
      thyroxine therapy should be given if the serum TSH level is higher than 10 mIU/L.
      For TSH values between 5 and 10 mIU/L, the decision for therapy should be
      individualized and depends on the level of TSH, presence of antithyroid
      antibodies, and clinical factors.

PMID- 11322359
TI  - Musical hallucinations associated with seizures originating from an intracranial
      aneurysm.
AB  - Hallucinations are defined as sensory phenomena in the absence of external
      sensory stimuli. Auditory hallucinations have been shown to arise from many
      different intracranial lesions, but seizures manifesting as musical
      hallucinations triggered by unruptured intracranial aneurysms are rare. We
      present a case of persistent, episodic musical hallucinations associated with
      seizures that led to the discovery of 2 small intracranial aneurysms. Typical
      electroencephalographic findings for seizure activity were observed but resolved
      after surgical clipping of the aneurysms. Concomitantly, the patient's
      hallucinations resolved. The literature on musical hallucinations is reviewed.

PMID- 11322360
TI  - Medical management of a large aortic thrombus in a young woman with essential
      thrombocythemia.
AB  - Aortic thrombus formation is rare in the patients with essential thrombocytosis
      (ET); therefore, no guidelines for its management have been established. Embolism
      from ET-associated large vessel thrombi is potentially lethal and has been
      managed surgically in a few reported cases. We describe herein a 45-year-old
      black woman with ET found to have a 3.5-cm, pedunculated intra-aortic thrombus at
      the thoracoabdominal junction. How to treat this potentially devastating aortic
      thrombus was a management dilemma. We believed, based on the patient's diagnosis
      of ET and the histology of similar thrombi in 1 reported series, that the aortic
      thrombus was a "white thrombus" consisting primarily of aggregated platelets with
      a minimal fibrin network and almost no entrapped erythrocytes. The patient was
      treated with aspirin, 325 mg daily, as a platelet antiaggregating agent and
      hydroxyurea, 1,500 mg daily, to reduce the platelet count to less than 450 x
      10(9)/L. The thrombus resolved without severe thromboembolic events. To our
      knowledge, this is the first reported case of a large intra-aortic thrombosis
      associated with ET that has been successfully managed with medical therapy alone.

PMID- 11322361
TI  - Mucosal ablation therapy of barrett esophagus.
AB  - Barrett esophagus is defined by the metaplasia of existing squamous mucosa into a
      specialized intestinal-type mucosa. The importance of this metaplasia is the
      association of this condition with the development of adenocarcinoma of the
      esophagus. Elimination of the metaplastic mucosa may decrease the cancer risk.
      Currently, several forms of therapy have evolved with the goal of replacing the
      specialized mucosa with normal squamous mucosa. These proposed treatments include
      photodynamic therapy and thermal techniques. The effectiveness of photodynamic
      therapy varies depending on the pharmaceutical photosensitizer used and the
      wavelength of light applied to activate the drug. Thermal techniques include
      multipolar coagulation, argon plasma coagulation, KTP:YAG laser therapy, Nd:YAG
      laser therapy, and argon laser therapy. Finally, mucosal resection has been
      attempted through the endoscope to remove large areas of the Barrett mucosa. All
      of these ablative strategies attempt to destroy the metaplastic mucosa and
      promote the regrowth of squamous epithelium. These therapies have demonstrated
      the ability to "reverse" the metaplasia to varying degrees, but a decrease in
      cancer risk has not been demonstrated conclusively with any of these treatment
      methods.

PMID- 11322362
TI  - Biomarkers in Barrett esophagus.
AB  - Barrett esophagus is a premalignant condition that may progress to
      adenocarcinoma. The risk of developing cancer has been estimated to be
      approximately 1 in 250 patient-years of observation; however, there appear to be
      subsets of patients at much higher risk. Risk stratification has previously been
      determined by histological identification of dysplasia. Several new biomarkers
      are being tested to help clinicians better determine the risk of cancer
      development. Although none of these biomarkers has been proven in a prospective
      study to predict the onset of cancer, they have been correlated with cancer
      development. Most of these are factors that have been associated with cancer
      development in other organs. These include assessment of cell proliferation,
      expression of cyclooxygenase 2, growth factors and oncogenes, secretory factors,
      cell cycle proteins, adhesion molecules, and aneuploidy and other genetic
      abnormalities. In addition to their role as potential cancer biomarkers, these
      factors have increasingly been reported as surrogate markers to monitor the
      effectiveness of conservative treatments for Barrett esophagus. In this article,
      biological markers are reviewed for their relevance in Barrett esophagus.
      Although most biological markers need to be evaluated further and, for most,
      prospective follow-up studies are lacking, at present abnormal ploidy status, P16
      and P53 gene abnormalities, or allelic losses are the most extensively
      documented.

PMID- 11322363
TI  - Images and reflections from Mayo Clinic heritage.

PMID- 11322364
TI  - Medical meteorology: whether weather influences admissions.

PMID- 11322365
TI  - Validation of PD Adequest 2.0 for pediatric dialysis patients.
AB  - Kinetic modeling has proven to be a valuable tool for peritoneal dialysis (PD)
      prescription in adult PD patients. The clinical application of this procedure has
      rarely been studied in children. We therefore evaluated the PD Adequest 2.0 for
      Windows program (Baxter Healthcare Co., Deerfield, IL) as a prescription aid for
      the management of pediatric PD patients by comparing the measured and predicted
      PD clearances, total drain volumes, and net ultrafiltration in 34 children (15
      males) (mean age 10.9 +/- 6.0 years) receiving long-term PD. In each case, a 4-h
      peritoneal equilibration test was conducted with a standardized test exchange
      volume of 1,100 ml/m2 BSA. A total of 43 24-h dialysate (plus urine in 12)
      collections were analyzed. The levels of agreement between measured and predicted
      values for weekly peritoneal and total urea Kt/V, weekly peritoneal and total
      creatinine clearance, daily drain volume, net ultrafiltration and daily
      peritoneal urea and creatinine mass removal were assessed with correlation
      coefficients (re) and Bland-Altman limits of agreement. The study revealed that
      there is a basic level of agreement between measured and modeled values for
      solute removal and total drain volume, with correlation coefficients ranging from
      0.75 to 0.98. In contrast, the rc for net ultrafiltration was only 0.34. The
      majority (75%) of patients had modeled urea and creatinine clearances that were
      within 20% of their measured values. These data suggest that the PD Adequest 2.0
      for Windows program can predict urea and creatinine clearances with reasonable
      accuracy in pediatric PD patients, making it a valuable resource in prescription
      management.

PMID- 11322366
TI  - Eighteen years experience in pediatric acute dialysis: analysis of predictors of
      outcome.
AB  - This study reviewed the 18-year experience of acute dialysis in the pediatric
      intensive care unit, in order to identify factors that could predict outcome, and
      to determine whether newer modalities of acute dialysis have influenced this
      outcome. Sixty-six children (ages 1 day to 19 years) received acute dialysis from
      May 1980 to April 1998. Factors predicting outcome were analyzed using univariate
      and Cox regression analysis. Modality of dialysis in the first 15 years was
      exclusively peritoneal dialysis. with a mortality of 63.9%. However, in the last
      3 years, with increasing patient numbers, continuous hemodiafiltration (CHDF) was
      the modality of choice (56.7%), with a mortality of 73.3%. Univariate analysis
      showed that age <1 year, coma, acute tubular necrosis, disseminated intravascular
      coagulopathy, assisted ventilation, and hypotension were associated significantly
      with poor outcome (P<0.05). Cox regression analysis revealed that mortality was
      significantly higher in patients on mechanical ventilation (RR 5.96, 95% CI 1.82
      19.50), or with age <1 year (RR 2.00, 95% CI 1.08-3.73). In conclusion, despite
      the increasing use of CHDF over the last 3 years, there was no significant
      improvement in mortality, probably related to the fact that more critically ill
      patients were dialyzed.

PMID- 11322367
TI  - Visual loss caused by pseudotumor cerebri in an infant on peritoneal dialysis.
AB  - Infants with chronic renal insufficiency have multiple risk factors for
      developing pseudotumor cerebri (PTC) and are at particular risk for being
      diagnosed with PTC late, because of their inability to express symptoms. We
      describe a 13-month-old infant dependent on peritoneal dialysis, without evidence
      of central nervous system infection or inflammation, who developed acute vision
      loss secondary to PTC. Signs of PTC in infants include torticollis,
      inattentiveness, inability to track, facial paresis, or new-onset strabismus.
      Physicians responsible for the care of children with renal failure should be
      aware of the potential for PTC, as the diagnosis should be made as early as
      possible to prevent permanent visual loss.

PMID- 11322368
TI  - Expression of the orpk disease gene during kidney development and maturation.
AB  - Further analysis of the orpk mouse model of human autosomal recessive polycystic
      kidney disease is providing more insight into the function of the Tg737 gene and
      the pathobiology of renal cystic disease. Here we have determined the temporal
      spatial profile of Tg737 expression and ascertained the profile of disease
      pathology utilizing Tg737delta2-3betaGal/+ and Tg737delta2-3betaGal/ Tg737orpk
      compound heterozygotes from embryonic day 13.0 (E13.0) to postnatal day 270
      (D270). This has allowed us to correlate disease progression and Tg737 expression
      in the context of the mutant orpk phenotype. These data reveal that Tg737 is
      dynamically regulated during kidney development and during postnatal kidney
      maturation in normal and in orpk mutants. This expression pattern correlates with
      the pathology of the disease, such that tubular segments with the highest
      expression levels are most protected from cystic disease. These data indicate
      that kidney tubules require a threshold level of Tg737 function for normal
      tubular development, structure, and function. In addition, these data demonstrate
      that the timing of cyst formation and severity of cyst progression is modulated
      differently in different regions of the nephron in this model.

PMID- 11322369
TI  - Pulmonary dysplasia, Denys-Drash syndrome and Wilms tumor 1 gene mutation in
      twins.
AB  - While a genetic basis for the association of developmental lung and kidney
      defects has been suspected, the involvement of specific genes in this process is
      under active investigation. We report such a possible genetic linkage present in
      identical twins with a mutant Wilms tumor (WT1) gene. Twin girls, born at 35
      weeks gestation, manifested symptoms of congenital nephrotic syndrome, renal
      failure, and severe respiratory abnormalities refractory to assisted ventilation.
      Both died at 1 month of age. Renal biopsies and autopsy kidney tissue from both
      the girls revealed diffuse mesangial sclerosis (DMS). Autopsy lung tissue
      revealed pulmonary dysplasia and hypoplasia in both twins. The WT1 gene from
      renal tissue in both twins was analyzed for mutations using polymerase chain
      reaction (PCR) amplification and the single-strand conformation polymorphism
      (SSCP) technique. Both twins possessed an identical missense mutation in exon 8
      of the WT1 gene, resulting in replacement of arginine by histidine at amino acid
      366 (arg366his) in the WTI protein. This mutation has previously been described
      in Denys-Drash syndrome. The WT1 gene plays a role in mesenchymal epithelial (ME)
      interactions in the developing urogenital system, and possibly has a similar role
      during lung morphogenesis. We propose that this WT1 gene mutation contributes to
      both DMS and developmental pulmonary abnormalities by altering ME interactions in
      both organs.

PMID- 11322370
TI  - The underlying diseases and follow-up in Taiwanese children screened by
      urinalysis.
AB  - To date, the underlying diseases and follow-up of Taiwanese children screened by
      urinalysis have not been reported. The grading of urine abnormalities varied from
      grade A (microscopic hematuria only), grade B (light proteinuria only), grade C
      (light proteinuria and microscopic hematuria) to grade D (heavy proteinuria).
      From January 1991 to August 1998, 630 students, aged 6-15 years and with positive
      urinary screening, were admitted to our hospital for further evaluation. Of
      these, 573 students had confirmed abnormal findings, 298 were boys, 275 were
      girls, and 294 students received a renal biopsy and have had regular follow-up
      visits. This study was designed to retrospectively elucidate: (1) the
      relationship between grading of urine abnormality and underlying disease; (2) the
      relationships among hypertension, grading of urine abnormality, and underlying
      disease; (3) the underlying disease of low serum C3 level; and (4) to determine
      whether urinary screening progressively decreased the number of students with end
      stage renal disease (ESRD) annually. The results show that glomerular nephritis
      (GN) is still one of the major causes of urinary abnormalities. The most
      important secondary GN was systemic lupus erythematosus (SLE) with lupus
      nephritis. One-quarter of the patients fulfilled at least four of the revised
      American Rheumatology Association (ARA) criteria for SLE at first administration,
      while the others who fulfilled only two to three of the revised ARA criteria had
      gradually developing signs and symptoms of SLE at follow-up. The percentage of
      SLE patients amongst anti-nuclear antibody (ANA) positive children was 72%.
      Membranoproliferative GN is very rare. The distribution of hypertension was 8.2%
      in grade A, 10.7% in grade B, 9.7% in grade C, and 28.9% in grade D urinary
      abnormality. There were statistical differences between grade D and either grade
      A or B or C (P<0.05). Lower serum C3 levels were found only in a minority of
      patients, including those with SLE. In this series, focal segmental glomerular
      sclerosis (FSGS) and active class IV lupus nephritis patients were found early
      enough to receive methylprednisolone pulse plus cyclosporine A therapy. To date
      there have been only 2 cases (5%) of FSGS with impaired renal function, and none
      of the lupus nephritis patients are in the predialysis stage. In conclusion, GN
      is still the major cause of urinary screening abnormality. ANA study is indicated
      in all Chinese students with abnormal urinary screening. The correlations between
      the severity of proteinuria and hypertension showed more-severe proteinuria in
      patients with nephritis as well as in those with hypertension.

PMID- 11322371
TI  - Progression after release of obstructive nephropathy.
AB  - Progressive glomerular and tubulointerstitial fibrosis develop in 1-year-old rats
      even after relief (R) of unilateral ureteral obstruction (UUO) at 5 days of age.
      The present study investigated whether a progressive renal injury model of UUO
      could be achieved after reversal of UUO (RUUO) in adult instead of neonatal rats.
      The potential for alpha-tocopherol modulation of mRNA for the fibrogenic
      cytokine, transforming growth factor-beta1 (TGFbeta1), apoptosis (TUNEL assay),
      and the presence of the stress protein, heat shock protein-70 (HSP-70), was also
      studied in this post-obstructive model. Male Sprague-Dawley rats weighing 125-150
      g were randomly assigned to groups of 4 animals each for durations of 7 or 14
      days of alpha-tocopherol supplementation after RUUO. The groups included: (i)
      sham, regular chow; (ii) RUUO, regular chow; (iii) RUUO, contralateral
      nephrectomy (NX); and (iv) RUUO, NX plus alpha-tocopherol supplementation. We
      found a significant increase in the ratio of kidney weight/body weight in the
      RUUO+NX group at 14 days compared with the sham and RUUO groups. This rise in the
      RUUO+NX group was significantly reduced after 14 days of alpha-tocopherol
      administration. The elevated level of kidney TGFbeta1 mRNA in the RUUO+NX group
      was only partially reduced at 7 days. But at 14 days this became significantly
      reduced with the continued alpha-tocopherol treatment. The HSP-70 staining and
      the apoptosis of the kidney showed results parallel to those of TGFbeta mRNA at
      14 days. To separate the effects of hypertrophy after unilateral NX from the RUUO
      studies, we carried out a second experiment in control animals subjected to NX,
      with and without alpha-tocopherol supplementation. Fourteen days after NX, the
      apoptosis and TGFbeta1 mRNA showed no significant differences from the control
      animals. Our data suggest that a model of progressive renal injury in RUUO can be
      established in adult rats. After contralateral NX, the progressive injury is
      evidenced by the increase in the ratio of kidney weight/total body weight, the
      apoptotic counts, as well as fibrogenic cytokine TGFbeta1 mRNA in the post
      obstructed kidney. Finally, our data also support the concept that alpha
      tocopherol is renal protective, as judged by TGFbeta1 mRNA, apoptosis, and HSP-70
      staining, even in the progressive disease process of the post-obstructed model.

PMID- 11322372
TI  - Pulse methylprednisolone treatment of idiopathic steroid-resistant nephrotic
      syndrome.
AB  - Although much of the interest in pulse methylprednisolone therapy (PMT) has
      centered around its use in children with focal segmental glomerulosclerosis, PMT
      has also been shown to be effective in the treatment of other proteinuric renal
      diseases. We hypothesized that a PMT-based treatment protocol, derived from the
      Tune-Mendoza protocol, would effectively induce a more rapid remission in young
      children with idiopathic steroid-resistant nephrotic syndrome (SRNS). A
      retrospective analysis was conducted of 11 consecutive SRNS patients (mean age
      3.6 +/- 1.5 years) that received PMT between 1 August 1992 and 1 May 1998. The
      initial mean urinary protein/urinary creatinine ratio (UP/UC, mg/mg) was 8.3 +/-
      9.7 and mean estimated creatinine clearance (CCr) 137.7 +/- 47.0 ml/min per 1.73
      m2. An average of 24.8 +/- 10.5 PMT doses were given. The mean duration of PMT
      therapy until remission was 23.4 +/- 29.9 days (median 12 days). Cyclosporine and
      cyclophosphamide were used to maintain and extend remissions in 5 and 4 patients,
      respectively. At the conclusion of the study, the mean UP/UC was 0.12 +/- 0.22
      and mean CCr 151.8 +/- 39.8 ml/min per 1.73 m2 (no CCr < or = 100 ml/min per 1.73
      m2). Of the 11 patients, 9 attained complete remission. Adverse effects were mild
      and infrequent. This PMT protocol appears to safely and effectively induce
      remission in young children with SRNS. A future prospective trial that evaluates
      the efficacy of PMT in young children with SRNS is warranted.

PMID- 11322373
TI  - Inferior vena cava indices determine volume load in minimal lesion nephrotic
      syndrome.
AB  - The pathogenesis of edema in nephrotic syndrome has not been entirely understood.
      We investigated the value of the echographic parameters [inferior vena cava index
      (IVCI), inferior vena cava collapsibility index (IVCCI), and left atrium diameter
      (LAD)] to determine the volume load in children with minimal lesion nephrotic
      syndrome (MLNS). Twelve children with MLNS (seven boys, five girls) were included
      in this study. The patients were classified into three different stages (stage A:
      edematous; stage B: 50% decrease in weight gain; stage C: edema free) following
      measurement of their ideal weights. The ideal weight of patients in stage A was
      increased 13 +/- 7%. Serum total protein, albumin and urine sodium levels were
      found to be low in these patients. Plasma renin activity (PRA) and serum
      aldosterone levels in stage A were significantly different from those of the
      control group (P<0.05). PRA and serum aldosterone levels were not different from
      those of the control group in stage B (P>0.05). However, the increase in PRA was
      significant in stage C. Although a significant weight decrease was found in
      stages B and C, it had no effect on IVCI, LAD, and cardiothoracic index. We
      consider IVCI, IVCCI, and LAD measurements by echocardiography (ECHO) to be easy
      and reliable clinical methods for assessing the intravascular volume load in
      patients with MLNS.

PMID- 11322374
TI  - Renal tubular dysfunction in epileptic children on valproic acid therapy.
AB  - To investigate the effects of valproic acid (VPA) on renal tubular function, we
      examined 15 ambulatory children with epilepsy who received VPA for at least 6
      months. None of the patients had mental retardation. Fourteen age- and sex
      matched children were used as a control group. No statistically significant
      differences were found between patients and control subjects with respect to
      blood urea nitrogen (BUN), creatinine (Cr), uric acid, creatinine clearance
      (Ccr), tubular reabsorption of phosphorus (TRP), urinary Ca:creatinine ratio,
      urinary pH and mean urinary beta2-microglobulin concentrations (P>0.05). Protein
      and glucose in patient urine samples were negative. Urine microscopic
      examinations and amino acid chromatographies of patients were also normal.
      However, significant differences were found between patient and control groups
      with respect to mean urinary N-acetyl-beta-D-glucosamine:creatinine ratio
      (NAG:Cr) and mean urinary malondialdehyde:creatinine (MDA:Cr) ratio (P<0.05). In
      conclusion, ambulatory children with epilepsy taking VPA therapy may develop
      proximal renal tubular dysfunction. Although this finding is clini-cally
      insignificant, it should be kept in mind during VPA therapy.

PMID- 11322375
TI  - Early prognostic factors of infants with chronic renal failure caused by renal
      dysplasia.
AB  - Renal dysplasia (RD) is a common cause of chronic renal failure (CRF) in
      children. The evolution towards end-stage renal failure is unpredictable due to
      the paucity of early prognostic factors. In order to identify early prognostic
      clinical criteria, we have retrospectively analyzed renal function and growth in
      11 infants with RD and CRF from birth up to 4 years of age. Children with
      obstructive RD were not included. Glomerular filtration rate (GFR) was estimated
      from Schwartz formula. In infants with a GFR below 15 ml/min per 1.73 m2 at 6
      months of age (group A, n=5), kidney function did not further improve; 4 reached
      end-stage renal failure between 8 months and 6 years of age. In contrast, infants
      with a GFR above 15 ml/min per 1.73 m2 at 6 months of age (group B, n=6)
      experienced a significant improvement in renal function during follow-up, and
      none required renal replacement therapy. During the first 3 months of life all
      infants with RD and CRF developed severe growth retardation. Between 6 months and
      4 years of age, children from group B grew significantly better than those from
      group A. In conclusion, our experience suggests that GFR, estimated from Schwartz
      formula at 6 months of age, is a useful prognostic factor in infants with RD and
      CRF. Infants with a GFR below 15 ml/min per 1.73 m2 are at risk of severe growth
      delay and the need for early renal replacement therapy, whereas those with a GFR
      above 15 ml/min per 1.73 m2 have a relatively favorable long-term prognosis.

PMID- 11322376
TI  - Acute necrotizing tubulointerstitial nephritis due to systemic adenoviral
      infection.
AB  - To date, all the reported cases of acute necrotizing tubulointerstitial nephritis
      (TIN) secondary to systemic adenovirus infection have occurred in individuals
      with primary or secondary immunodeficiency, and have resulted in renal failure
      and death. We present the case of a 12-year-old, immunologically competent girl
      who developed acute necrotizing TIN with acute renal failure (ARF), hepatitis and
      meningoencephalitis secondary to a systemic adenoviral infection who completely
      recovered with supportive care.

PMID- 11322377
TI  - Familial inheritance of crossed fused renal ectopia.
AB  - A family with dominant inheritance of a rare renal malformation is reported. The
      father and one son had left crossed fused ectopic and dysplastic kidneys and
      another son had a horseshoe kidney and vesicoureteral reflux. We discuss various
      potential pathogenetic mechanisms and propose that a defect in the timing of the
      proper reciprocal induction of the ureteric bud and the metanephric blastema is
      involved.

PMID- 11322378
TI  - A meta-analysis of cytotoxic treatment for frequently relapsing nephrotic
      syndrome in children.
AB  - For over 30 years cyclophosphamide (CYC) and chlorambucil (CHL) have been used to
      treat children with relapsing steroid-sensitive nephrotic syndrome (SSNS). A meta
      analysis on treatment protocols, efficacy, and side effects of CYC and CHL was
      performed from the literature. Thirty-eight studies comprising 1,504 children and
      1,573 courses of cytotoxic drug therapy were systematically evaluated. Relapse
      free survival rates increased with the cumulative dosage of CHL and CYC and were
      higher in children with frequently relapsing than steroid-dependent NS. The
      fatality rate of the treatment was approximately 1%. Leukopenia occurred in one
      third of patients treated with either drug. Severe bacterial infections developed
      in 1.5% of the patients under CYC and in 6.8% under CHL. Seizures were observed
      in 3.6% of children treated with CHL. Malignancies were observed in 14 children
      after high doses of either drug. Females rarely developed permanent gonadal
      damage. However, no safe threshold for a cumulative amount of CYC was found in
      males, but there was a marked increase in the risk of oligo- or azoospermia with
      higher cumulative doses. From this meta-analysis we recommend CYC 2-3 mg/kg body
      weight for 8-12 weeks as the standard scheme. CHL has higher rates of severe side
      effects and should be considered a second-line drug.

PMID- 11322379
TI  - Pathogenesis of edema formation in the nephrotic syndrome.
AB  - Based on observations in 110 children with nephrotic syndrome (NS) and data from
      the literature, existing concepts on the pathogenesis of edema formation in the
      NS have been modified. The data suggest that the basic abnormality is a primary
      disturbance in renal sodium excretion. Depending on the stage in the development
      of the NS, the rate of progression in the development of hypoproteinemia, and the
      absolute levels of plasma oncotic pressure, functional hypovolemia may develop,
      resulting in stimulation of hemostatic mechanisms and secondary sodium retention.
      This applies as much to patients with minimal change NS as to patients with
      histological lesions. Alterations in kidney function (glomerular filtration rate,
      renal plasma flow, filtration fraction) in the NS cannot be explained by hypo- or
      hypervolemia, but reflect variations in plasma oncotic pressure and glomerular
      basement membrane permeability. These abnormalities will also influence sodium
      excretion. Evaluation of the presence of functional hypovolemia will have
      therapeutic consequences. A quick diagnosis can be made by assessment of FENa+
      and UK+/ (UK+ + UNa+) Sodium retention associated with increased distal Na/K
      exchange indicates functional hypovolemia, and may be treated by albumin infusion
      if clinically required.

PMID- 11322380
TI  - Control of glomerular capillary development by growth factor/receptor kinases.
AB  - Multiple signaling processes, including cell-matrix and cell-cell interactions,
      and growth factor/receptor binding, are crucially important for guiding blood
      vessel formation. Here we summarize current data, much of which has been obtained
      recently from gene targeting in mice, on the roles played by the growth factor
      ligand/ receptor tyrosine kinase systems represented by: vascular endothelial
      growth factor (VEGF) and its receptors; Eph/Ephrins; Tie1, Tie2 and
      angiopoietins; and platelet-derived growth factor (PDGF) in glomerular capillary
      development. A fundamental understanding of glomerular endothelial growth and
      differentiation during organogenesis may provide clues for stimulating glomerular
      repair after toxic injury or ischemia.

PMID- 11322381
TI  - Glypicans and the biology of renal malformations.
AB  - The molecular mechanisms that control renal development are largely undefined.
      The discovery of mutations in the gene encoding glypican-3 (Gpc3) in humans with
      Simpson-Golabi-Behmel syndrome (SGBS) and renal dysplasia, and the establishment
      of a genetic mouse model of GPC3 deficiency has provided an opportunity to define
      the role of GPC3 during renal development. Glypicans are a family of cell surface
      heparan sulfate proteoglycans that control growth factor signalling in nonrenal
      tissues. Mutational inactivation of Gpc3 causes somatic overgrowth and cystic
      renal dysplasia, as observed in SGBS. Overgrowth of the ureteric bud and its
      branches and increased ureteric bud cell proliferation is observed during the
      early stages of renal development. Subsequently, during corticomedullary
      differentiation, cortical collecting duct cell proliferation is increased, while
      medullary collecting duct cells proliferate at a reduced rate and undergo
      apoptosis resulting in degeneration of the medulla. However, cells that
      constitute medullary cysts are characterized by enhanced cell proliferation and a
      lower rate of apoptosis. Thus, the phenotype arising from Gpc3 inactivation
      demonstrates that tight regulation of cell proliferation and apoptosis is
      critical during formation of the renal medulla.

PMID- 11322382
TI  - Angiotensin converting enzyme inhibitor-induced angioedema: report of a further
      case.

PMID- 11322383
TI  - 3-Dimensional organization of the N-terminal vinculin head fragment.
AB  - The cytoskeleton-associated protein vinculin is composed of a globular head and
      an elongated tail domain. The protein can be cleaved by V8 protease treatment
      into two fragments with apparent molecular masses of 90 and 29/27 kDa,
      respectively. So far, no high-resolution data on the tertiary structure of the N
      terminal 90-kDa fragment are available. We analyzed the 90-kDa fragment in
      detail, using electron spectroscopic imaging in conjunction with modelling
      experiments. The front view projection of this fragment appears roughly
      rhomboidal, with 4 intensity maxima arranged at the vertices and a stain-filled
      region in the center. Based on a detailed examination of different particle
      projections, a 3-dimensional model was constructed which appears as a flattened
      tetrahedron. A comparison of the 90-kDa fragment with the intact protein allows
      for a correlation between the subdomain organization of the vinculin head and the
      biochemically defined V8 protease cleavage sites (aa 851 and 857).

PMID- 11322384
TI  - Lovastatin blocks basic fibroblast growth factor-induced mitogen-activated
      protein kinase signaling in coronary smooth muscle cells via phosphatase
      inhibition.
AB  - We have recently reported that the activation of mitogen-activated protein kinase
      (MAPK) through specific protein kinase C (PKC) isoforms is required for basic
      fibroblast growth factor (bFGF)-induced proliferation of coronary smooth muscle
      cells (cSMC). In this study, we investigated the effects of the 3hydroxy-3-methyl
      glutaryl coenzyme A (HMG CoA) reductase inhibitor lovastatin on bFGF-induced
      signal transduction in cSMC. The present study shows that lovastatin inhibits
      bFGF-stimulated DNA synthesis in cSMC, and that this inhibition is reversed by
      mevalonate (50 micromol/l) and by geranylgeranyl-pyrophosphate (1-5 micromol/l).
      Although lovastatin prevented Ras farnesylation the amount of bFGF-stimulated
      MAPK phosphorylation decreased only partially after lovastatin treatment. In
      addition, lovastatin pretreatment resulted in a sustained phosphorylation of
      MAPK. We observed a dose-dependent lovastatin-dependent increase in PKC activity,
      which could be prevented by mevalonate. This increase was comparable to the one
      induced by calyculin A (2 nmol/l), an inhibitor of protein phosphatase PP-1 and
      PP-2A. Lovastatin inhibited the expression of the PP-1 protein, which is involved
      in bFGF-induced DNA synthesis in cSMC. Thus, our data suggest that, lovastatin
      possibly affects the dephosphorylation processes of PKC and MAPK by inhibition of
      PP-1/PP-2A protein phosphatases which are involved in the bFGF-induced
      mitogenesis in cSMC.

PMID- 11322385
TI  - Alternative activation of extracellular signal-regulated protein kinases in
      curcumin and arsenite-induced HSP70 gene expression in human colorectal carcinoma
      cells.
AB  - We have investigated the regulation mechanism of chemical stress-induced HSP70
      gene expression in human colorectal carcinoma cells (COLO205 and HT29). Our data
      show that chemical treatments including sodium arsenite and curcumin, induced
      significant synthesis of HSP70 and its mRNA. The induced HSP70 gene expression
      appears to be increased at the transcriptional level. The increase in HSP70 gene
      expression by both chemicals is associated with an increase in HSF binding to HSE
      and induction of HSF1 di- or trimerization. Phosphorylation and activation of
      extracellular signal-regulated proteins (ERK1/2) were detected in sodium arsenite
      treated COLO205 and HT29 cells, and the free radical scavenger N-acetyl-L
      cysteine (NAC) was able to inhibit this ERK1/2 activation and HSP70 gene
      expression. MAPK blockade by the specific MEK1 inhibitor (PD98059) decreased the
      ability of sodium arsenite to increase HSP70 gene expression in a dose-dependent
      manner along with dephosphorylation of ERK1/2 proteins. In contrast to arsenite
      treatment, activation of ERK1/2 was not detected in curcumin-treated colorectal
      carcinoma cells, and NAC and PD98059 did not show any inhibitory effect on HSP70
      gene expression induced by curcumin. Overexpression of a dominant negative mutant
      of mitogen-activated protein kinase kinase kinase 1 (MEKK1-DN) prevents arsenite
      induced ERK1/2 phosphorylation and HSP70 protein synthesis. These results
      indicated that the ERK signaling pathway can participate in HSP70 gene expression
      induced by the prooxidant sodium arsenite, but not by the antioxidant curcumin.

PMID- 11322386
TI  - Rat germinal cells require PARP for repair of DNA damage induced by gamma
      irradiation and H2O2 treatment.
AB  - The ability of rat germinal cells to recover from genotoxic stress has been
      investigated using isolated populations of primary spermatocytes and round
      spermatids. Using a comet assay at pH 10.0 to assess single strand breakage (SSB)
      in DNA, it was found that a high level of damage was induced by 5 Gy gamma
      irradiation and acute exposure to 50 microM H2O2. This damage was effectively
      repaired during a subsequent recovery period of 1-3 hours culture in vitro but
      repair was significantly delayed in the presence of the poly(ADP
      ribose)polymerase (PARP) inhibitor 3-aminobenzamide (3-ABA). Immunofluorescence
      detection of PARP with specific antibodies localised the protein to discrete foci
      within the nucleus of both spermatocytes and spermatids. Poly(ADP-ribose) (pADPR)
      could also be detected in spermatid nuclei following gamma-irradiation or H2O2
      treatment. Moreover, PARP activation occurs both in spermatocytes and spermatids
      left to recover after both genotoxic stresses. The NO donors, 3-morpholino
      sydnonimine (SIN-1) and S-nitrosoglutathione (SNOG), caused significant SSBs in
      both spermatocytes and spermatids. The effects of SIN-1 could be prevented by
      exogenous catalase (CAT), but not superoxide dismutase (SOD), in the cell
      suspensions. SNOG-induced SSBs were insensitive to both CAT and SOD. It is
      concluded that DNA in spermatocytes and spermatids is sensitive to damage by
      gamma-irradiation and H2O2 and that efficient repair of SSBs requires PARP
      activity.

PMID- 11322387
TI  - Detection of elevated caspase activation and early apoptosis in liver diseases.
AB  - Apoptosis has been implicated in the pathogenesis of many diseases including
      various forms of liver failure. The apoptotic process is essentially regulated by
      intracellular proteases, called caspases, which cleave several vital proteins.
      Despite the rapid elucidation of apoptotic signaling cascades, however, almost no
      information exists about the activation of caspases in situ. In the present
      study, a monoclonal antibody was employed which selectively recognized cleavage
      site-specific fragments of the caspase substrate cytokeratin-18. We demonstrate
      that this antibody labeled apoptotic hepatocytes in culture and, in addition,
      could be used to monitor caspase activation in formalin-fixed tissue biopsies. In
      liver sections of different liver diseases an increased number of early apoptotic
      cells was detected which were not found in normal tissue. Our data reveal that
      hepatobiliary diseases are characterized by elevated caspase activation and
      apoptosis, which can be specifically detected in situ by a cleavage site-specific
      antibody against cytokeratin-18.

PMID- 11322388
TI  - Role of myosin-II phosphorylation in V12Cdc42-mediated disruption of Drosophila
      cellularization.
AB  - Microinjection of constitutively active Cdc42 (V12Cdc42) disrupts the actomyosin
      cytoskeleton during cellularization (Crawford et al., Dev. Biol., 204, 151-164
      (1998)). The p21-activated kinase (PAK) family of Ser/Thr kinases are effectors
      of GTP-bound forms of the small GTPases, Cdc42 and Rac. Drosophila PAK, which
      colocalizes with actin and myosin-II during cellularization, concentrates at
      sites of V12Cdc42-induced actomyosin disruption. In vitro biochemical analyses
      demonstrate that PAK phosphorylates the regulatory light chain (RLC) of
      Drosophila nonmuscle myosin-II on Ser21, a site known to activate myosin-II
      function. Although activated PAK does not disrupt the actomyosin cytoskeleton, it
      induces increased levels of Ser21 phosphorylated RLC. These findings suggest that
      increased levels of RLC phosphorylation do not contribute to disruption of the
      actomyosin hexagonal array.

PMID- 11322389
TI  - Tissue-specific neuro-glia interactions determine neurite differentiation in
      ganglion cells.
AB  - Guided formation and extension of axons versus dendrites is considered crucial
      for structuring the nervous system. In the chick visual system, retinal ganglion
      cells (RGCs) extend their axons into the tectum opticum, but not into glial
      somata containing retina layers. We addressed the question whether the different
      glia of retina and tectum opticum differentially affect axon growth. Glial cells
      were purified from retina and tectum opticum by complement-mediated cytolysis of
      non-glial cells. RGCs were purified by enzymatic delayering from flat mounted
      retina. RGCs were seeded onto retinal versus tectal glia monolayers. Subsequent
      neuritic differentiation was analysed by immunofluorescence microscopy and
      scanning electron microscopy. Qualitative and quantitative evaluation revealed
      that retinal glia somata inhibited axons. Time-lapse video recording indicated
      that axonal inhibition was based on the collapse of lamellipodia- and filopodia
      rich growth cones of axons. In contrast to retinal glia, tectal glia supported
      axonal extension. Notably, retinal glia were not inhibitory for neurons in
      general, because in control experiments axon extension of dorsal root ganglia was
      not hampered. Therefore, the axon inhibition by retinal glia was neuron type
      specific. In summary, the data demonstrate that homotopic (retinal) glia somata
      inhibit axonal outgrowth of RGCs, whereas heterotopic (tectal) glia of the
      synaptic target area support RGC axon extension. The data underscore the pivotal
      role of glia in structuring the developing nervous system.

PMID- 11322390
TI  - Our "idees fixes" in rhinoplasty: the naso-frontal angle and the alar lateral
      crus.
AB  - An examination of the naso-frontal angle shows that a cranial or caudal shift in
      position affects the dorsum length. The fundamental aspect characterizing the
      naso-frontal angle is its width: it may be normal, too wide, or too narrow. It's
      easier to modify a too-narrow angle than a too-wide one. We show surgical
      techniques, emphasizing their method applied to the over-wide angle. The second
      "idee fixe" is the morphology of the alar lateral crus. Every variety of this
      structure has a peculiar property of shape and relationship with other elements
      that predetermines the therapeutic action. Diagrams and photographs are shown to
      describe the surgical techniques and the clinical results. There is also a
      demonstration of the method for alar lateral crus resection, which we call "the
      long keel shape," since it resembles the shape of a sailboat keel.

PMID- 11322391
TI  - Repair of full thickness defect of the nose using an expanded forehead flap and a
      glabellar flap.
AB  - We describe a method to repair full thickness defects of the nose using a
      glabellar flap as the lining of the nasal cavity and an expanded forehead flap
      for external closure. We consider our method useful in the reconstruction of a
      nose with a full thickness defect for which the flap donor site is limited. The
      patient was a 45-year-old man who underwent resection of a basal cell carcinoma
      located over the dorsum of the nose which was associated with a hemangioma
      simplex on the face. As a result, about two-thirds of the nose, from the dorsum
      to the tip, as well as a part of the right cheek became deficient and the right
      nasal cavity became exposed. The nose was reconstructed using the above-mentioned
      method. The result was satisfactory both cosmetically and functionally.

PMID- 11322392
TI  - Scanning electron microscopic study on double and single eyelids in Orientals.
AB  - The conventional theory is that Occidentals have a terminal insertion of the
      levator aponeurosis at the anterior portion, resulting in a double eyelid,
      whereas in Orientals this fiber is not present, and therefore results in a single
      eyelid have been anatomically demonstrated. However, there have been more than a
      few reports indicating that the anatomical difference between a single eyelid and
      double eyelid in Orientals cannot be explained by this theory. Therefore, in
      order to verify the direction of the levator aponeurosis in the eyelids of
      Orientals, we observed Japanese eyelids using a scanning electron microscope
      (SEM). As a result of three-dimensional, cross-sectional observations using SEM,
      we were able to confirm the existence of a branch of the levator aponeurosis that
      runs through the layer of the orbicularis oculi muscle and connects with the
      levator aponeurosis in the double eyelid, as in the occidental eyelid. This was
      not seen in the single eyelid. It is thought that this new anatomical finding
      will become an important fundamental for double eyelid operations in Orientals.

PMID- 11322393
TI  - Lip reconstruction of comparatively large defect including the commissure using
      remaining lip tissue: a modification of reconstructed method.
AB  - We present two reconstructed cases after malignant skin tumor of comparatively
      large defects of lip including the commissure using remaining lip tissue alone.
      After resecting a tumor including wedge-shaped full-thickness lip tissue, a full
      thickness oblique incision is made at the site 5 mm distant from the
      contralateral commissure. The rhomboid-shaped lower lip flap is created,
      transposed to the defect, and sutured with the defect margin, including the upper
      lip, to reconstruct the commissure. The cross lip flap is created at the
      contralateral side of the lower lip, 5 mm from the commissure, and the defect is
      closed with the crosslip flap. Although our method is applicable only to selected
      cases, we believe that it is useful in terms of maintaining symmetry of the lip
      and function of the commissure in the reconstruction of comparatively large
      defects including the commissure.

PMID- 11322394
TI  - Centrofacial lifting, up to date.
AB  - The centrofacial lifting is a procedure that has proved its benefits and
      advantages for treating the aging effects on the centrofacial area. The author
      presents the procedure that he is using currently, with technical details and
      maneuvers developed to get better results. With the experience of 664 cases in 10
      years, indications, complications, and long-term results are presented.

PMID- 11322395
TI  - The forehead lift: endoscopic versus coronal approaches.
AB  - Rejuvenation surgery of the upper one-third of the face can be accomplished by a
      number of well-known techniques and approaches. The objectives of this study were
      to: (1) determine if endoscopic-assisted forehead lifts achieve the same degree
      of correction as the coronal/pretrichial forehead lifts, (2) to assess the effect
      of concurrent blepharoplasty on brow elevation, and (3) to evaluate long-term
      results of coronal/ pretrichial forehead lifts. The study was a retrospective
      blinded comparison of pre- and postoperative photographs of patients who
      underwent forehead lifts. In order to control for the differences in photographs,
      ratios of distances were measured utilizing standard anthropometric sites of the
      brow, medial canthus, and subnasale. All reviewed cases were operated on by the
      same surgeon (S.W. Perkins, M.D.). A total of 140 patients having undergone
      forehead lift procedures and with 12-month postoperative photographic
      documentation were included in the study. Of these 121 patients had coronal
      forehead lifts and 19 had endoscopic-assisted forehead lifts. Results revealed
      that at 1 year follow-up both methods achieved brow elevation without a
      significant difference in the approach. Concomitant blepharoplasty had no
      statistical effect on brow position. Additionally, long-term follow-up on the
      coronal/pretrichial lifts revealed a gradual drop in brow position over 5 years.
      We conclude that both endoscopic and coronal/pretrichial forehead lifts provide
      for comparable elevation at 1-year follow-up. Concomitant blepharoplasty has
      minimal to no significant effect on brow position. Brow elevation in
      coronal/pretrichial forehead lifts may be temporary.

PMID- 11322396
TI  - Modification of vertical scar in vertical mammaplasty technique.
AB  - Vertical mammaplasty is a simple and safe procedure that relies on an upper
      pedicle to the areola with lower central breast reduction and glandular shaping.
      We applied this technique to six patients adding a modification of the vertical
      scar which distributed skin tension both to the areola and vertical suture line.
      It prevented an unacceptable puckering vertical scar and enlargement of areola.
      This modification also provided satisfactory breast shape with a good vertical
      scar especially at the early postoperative period.

PMID- 11322397
TI  - Rupture of Trilucent-type breast implants: a clinical case.
AB  - We present the case of a patient who underwent cosmetic breast augmentation in
      1996, with Trilucent-type implants. Four years later, there were delayed
      complications inherent in the implants, which caused serious clinical problems.

PMID- 11322398
TI  - Laser punch-out for acne scars.
AB  - Patients with acne scars want smooth facial skin. However, achieving this is
      difficult with dermabrasion or chemical peeling. Nor can acne scars be covered
      with cosmetics, due to their ice-picked or cobblestone appearance. Laser
      resurfacing is more effective and safer than other conventional methods due to
      its precision with depth control and variable methods of surface cutting. Even
      depth resurfacing with a laser shows unsatisfactory results, therefore, for the
      deep-sited acne scar the cutting methods have to be changed according to the
      depth and pattern of the scar. For 2 years, starting in January 1996, we treated
      71 patients with a high-powered CO2 laser (Ultrapulse). Different resurfacing
      methods were applied according to the depth and pattern of the scars. For mild
      depressed scars, even depth resurfacing was done. For moderate-depth acne scars,
      the shoulder technique was also used. For the deepest and ice-picked scars, the
      laser punch-out was combined. Laser resurfacing was carried out at 300-500 mJ,
      with two to five passes. Laser punch-out was done at 500 mJ, with three to seven
      continuous passes on the ice-picked scar. From the pathologic findings of acne
      scars showing that there was thick intradermal scar, we knew that laser punch-out
      was necessary for improvement of acne scars. Depth-wide, the ice-picked scars
      improved by over 80% and the sharp demarcated margin of the acne scar faded out.
      Most of the patients with acne scars were satisfied with laser resurfacing. Only
      six patients had a second laser treatment, with an interval of 12 months. There
      were no hypertrophic scars after laser resurfacing, but erythema lasted for 3-12
      months. Patients taking oral retinoic acid were not contraindicated for laser
      resurfacing but required special caution because they had atrophic skin and
      delayed wound healing. Laser resurfacing is the most versatile method for acne
      scars, with a high-powered CO2 laser. The laser punch-out method is better than
      even depth resurfacing for improving deep acne scars and can be combined with the
      shoulder technique or even depth resurfacing according to the type of acne scar.

PMID- 11322399
TI  - Treating a sebaceous cyst: an incisional technique.
AB  - The author describes an incisional technique for removing a sebaceous cyst. This
      technique considerably reduces the size of the cyst, and if excision of the
      balance of the cyst is later pursued, the resulting scar is not as conspicuous as
      the scarring that occurs from conventional excisional surgery.

PMID- 11322400
TI  - Histomorphologic and volumetric analysis of implanted autologous preadipocyte
      cultures suspended in fibrin glue: a potential new source for tissue
      augmentation.
AB  - Previous efforts to use adipocyte transplants for tissue augmentation have been
      limited by high and unpredictable resorption rates. Preadipocytes are precursor
      cells that are capable of replication and differentiation into mature adipocytes.
      Furthermore, they are more resilient to ischemia, making them a desirable
      transplant media. Utilizing fibrin glue as a transport vehicle and a
      prefabricated intramuscular capsule pouch as the recipient site, we have
      demonstrated the successful transplantation of cultured preadipocytes without the
      previously presented resorption sequelae. Histological analysis at 2 weeks has
      demonstrated establishment of vascular supply and the complete resorption of
      fibrin glue. Most importantly, using planimetric analysis, volume retention has
      been demonstrated in implanted areas up to 1 year following implantation.
      Finally, BrdU labeling has been utilized to demonstrate the lack of increased and
      uncontrolled replication rate, an index of potentially tumorigenic tissue. In
      conclusion, we have demonstrated a potentially new and safe source of tissue
      augmentation in the rat model.

PMID- 11322401
TI  - Preoperative identification of psychiatric illness in aesthetic facial surgery
      patients.
AB  - The purpose of this study was to evaluate the preoperative use of a two-part
      standardized assessment program (Prime-MD, Biometrics Research Department, New
      York State Psychiatric Institute) to objectively detect psychiatric disorders in
      facial plastic surgery patients, and to compare its use to findings identified by
      the facial plastic surgeon. Seventy-five new patients requesting aesthetic facial
      surgery at two academic centers and two private practice locations were
      evaluated.

PMID- 11322402
TI  - Lambda-shaped implant for augmentation of anterior nasal spine in Asian
      rhinoplasty as an ancillary procedure.
AB  - There is often a preexisting acute columella-labial angle in Asian noses and in
      most of these cases, the nasal spine is underdeveloped or sometimes even absent.
      Moreover, nasal tip projection by a tip graft or cephalic rotation of the nasal
      tip may get worse at the retracted columella-labial junction in the Asian nose
      with an underdeveloped anterior nasal spine, thus requiring the use of a
      maxillary spine graft or an implant. In many instances, however, the ideal source
      of autogenous tissue may not be available or the donor site for these tissues may
      be objectionable. So I have designed the lambda-shaped silicone implant for
      augmenting the underdeveloped anterior nasal spine (ANS) to correct the acute
      columella-labial angle. From March, 1996 until September, 1999, I have done ANS
      augmentations using the lambda-shaped silicone implant in Asian rhinoplasty on 37
      female patients. The correction of an acute columella-labial angle was readily
      accomplished by application of the lambda-shaped implant using the unilateral
      intranasal approach. The author suggests that ANS augmentation with the lambda
      shaped implant is a simple and effective method as an ancillary procedure in
      Asian rhinoplasty providing esthetically pleasing results in properly selected
      Asian patients.

PMID- 11322403
TI  - Ideas of distorted ethnic identity in 43 cases of psychosis.
AB  - OBJECTIVE: Distorted ethnic identity is a difficult concept to define, but
      relates to individuals from one ethnic group thinking that they want to belong to
      another ethnic group or that they do so already, but have been "misattributed" to
      the wrong category. The aim of the present study is to study descriptions of
      these behaviours. METHOD: Patients admitted to three hospitals in London were
      screened by the respective teams looking after them and case notes studied. No
      direct interviews were carried out. RESULTS: A total of 43 cases were identified.
      A large proportion were African-Caribbean males who fulfilled the criteria for
      DSM-IV diagnosis of paranoid schizophrenia. Female patients were more likely to
      use extreme measures to alter their appearance. CONCLUSIONS: Majority white
      culture may influence vulnerable patients who have psychoses to incorporate a
      range of ideas of distorted ethnic identity in their psychopathology.

PMID- 11322404
TI  - A cross-cultural study of parental conflict and eating disorders in a non
      clinical sample.
AB  - Previous British studies have found that EAT scores of second generation British
      Asian schoolgirls are higher than those of White schoolgirls (Furnham & Husain,
      1999; McCourt & Waller, 1995; Mumford et al., 1991), and that these scores are
      positively associated with parental over-protection (Furnham & Hussain, 1999).
      This study looked at the relationship between parental conflict and parental
      overprotection and EAT scores in three cultures. The three groups, all of late
      adolescent females, were British Caucasians (N=116), immigrant British Asians
      from Pakistan (N= 118), and Pakistanis tested in Pakistan (N=114). A 22 item
      conflict questionnaire was constructed and administered to 355 participants,
      along with the PBI, EAT-26, and Body Shape Belief Scale (BSBS). It was predicted
      that the British Asians would have higher EAT, parental protection and conflict
      scores than the other two groups. It was also predicted that EAT scores would be
      highly correlated with conflict scores. All hypotheses were supported, and over
      protection scores were noticeably highest in the British Asian group. They also
      had a significant amount of more conflict with parents than any of the other
      cultural groups. EAT scores were associated with conflict and over-protection.
      Results are discussed in terms of the literature in the field.

PMID- 11322405
TI  - The social functioning of persons with chronic mental illness: an empirical
      typology of consumers and correlates of social functioning.
AB  - This study examined the typology of consumers and correlates of their social
      functioning using the Social Functioning Scale (SFS). Data were obtained from 244
      outpatients of two psychiatric hospitals and psychiatric ward inpatients in two
      general hospitals through a structured in-person interview. The typology was
      generated using Cluster Analysis, and the profile of each group was further
      examined. The results indicated that there were four distinct groups of
      consumers. Multiple regression analysis revealed that consumers' sex, age,
      education, diagnosis, behavioral problems, family caregivers' age, employment
      status, and overall social support were significantly associated with consumers'
      social functioning. The implications for previous research findings and
      psychiatric rehabilitation service are discussed.

PMID- 11322406
TI  - Psychotic consciousness.
AB  - ABSTRACT Congruent with recent demands for greater attention to be given to
      patients' actual experiences at a fine-grained level in the understanding of
      psychosis (e.g. Thomas 1997) the present paper first describes one day in an
      actual psychotic episode suffered by the author in 1979 and then subjects this
      narrative to analytic and normalisation interpretations. It is suggested that
      acute psychotic thinking of paranoid form is critically mediated by real social
      events and by intrapsychic deficits in attentional capacity; metacognition;
      thought regulation and signal discriminative ability. Cognitive processes in
      delusion however, are suggested to be influenced by the presence of a threatening
      external locus of control. This reflects the strong social and political quality
      to delusional suffering. The effects therefore of victimisation on cognitive
      processes is suggested to be an important issue in social cognitive psychology
      and psychiatry.

PMID- 11322407
TI  - Costs and characteristics of heavy inpatient service users in outer London.
AB  - "Heavy users" is a new term often used to describe those who occupy a
      disproportionate number of psychiatric beds. In this study we identified the
      heaviest 10% (193) inpatient service users in one London borough over a 6 year
      period and compared these with a control group of 400 ordinary inpatient users. A
      weighting index was used to combine frequency of admission with duration. Heavy
      users were diagnostically and demographically similar to ordinary inpatient
      service users and only differed by their extensive use of services, about 3 times
      more than ordinary users in terms of health care costs, during the measured year.
      Their heavy use mainly depended on occupying hospital beds, and their use of
      outpatient, day patient and community services was relatively light.

PMID- 11322408
TI  - Mental health in Asia: social improvements and challenges.
AB  - Remarkable improvements in economic conditions and a considerable upgrade in the
      quality of life have been observed in many parts of Asia during the past several
      decades. At the same time, many mental health challenges face the people of Asia.
      Various social mental health indexes are reviewed here, with available data from
      China, Japan, Korea, Singapore, Malaysia, and other Asian societies. The data are
      compared with data from the United States, Australia in the Pacific Rim, and some
      other Western countries to examine patterns of similarity or difference between
      East and West in the process of modernization. Common trends in mental health
      issues associated with rapid sociocultural change observed in different Asian
      societies are discussed, as well as the relative shortage of mental health
      personnel available in many Asian societies. It is emphasized that, in addition
      to expanding psychiatric services, there is an even more urgent need to promote
      mental health knowledge and concern through education in the general population.
      Mental health needs to be cultivated and maintained by social forces and cultural
      strengths. It is stressed that there is a challenge for Asian people to advance
      mental health beyond economic development in the 21st century.

PMID- 11322409
TI  - Deep lamellar endothelial keratoplasty in the first United States patients: early
      clinical results.
AB  - PURPOSE: To report the early clinical results of the first U.S. patients to
      undergo deep lamellar endothelial keratoplasty (DLEK) surgery for the treatment
      of endothelial dysfunction. METHODS: Two patients with pseudophakia with Fuchs'
      endothelial dystrophy, under an Institutional Review Board-approved protocol,
      underwent replacement of the endothelium through a limbal, scleral pocket
      incision (DLEK). Their vision, pachymetry, and corneal map topography were
      measured in the early postoperative period and were compared with preoperative
      measurements. RESULTS: Both patients had improvement in all parameters within 1
      month after surgery, and corneal topography showed no significant change from
      before the surgery. The first patient's vision at 6 months was 20/40 (+2) with a
      0.75-diopter (D) decrease in astigmatism and a normal pachymetry of 573 microm.
      The second patient's vision at 6 months was 20/40 (-2) with a 0.25-D increase in
      astigmatism and a pachymetry of 618 microm. Graft endothelial cell counts at 6
      months were 1,692 and 2,631 cells/mm2, respectively. CONCLUSION: The DLEK
      procedure, with its absence of corneal surface incisions and sutures, preserves
      the preoperative topography and demonstrates good donor endothelial cell count
      and function early in the postoperative period. If interface clarity can be
      maintained, the potential advantages over penetrating keratoplasty in the
      treatment of endothelial dysfunction are considerable.

PMID- 11322410
TI  - Impression cytology study of conjunctival epithelial phenotypes on the healing
      ocular surface after pterygium excision.
AB  - PURPOSE: To compare the process of conjunctival epithelial regeneration after
      three types of pterygium excision procedures. METHODS: Thirty-eight patients (45
      eyes) with primary pterygium were randomly assigned to a bare-sclera procedure
      (group 1, 15 eyes of 12 patients), bare-sclera with intraoperative mitomycin C
      (MMC 0.02% for 30 seconds; group 2, 15 eyes of 14 patients), or pterygium
      excision with conjunctival autografting (group 3, 15 eyes of 12 patients).
      Controls were healthy fellow eyes and seven eyes of age- and sex-matched
      subjects. Impression cytology was performed preoperatively, at 1 and 2 weeks, and
      at 1, 3, 6, and 12 months after surgery. The nucleus-to-cytoplasm (N/C) ratio of
      nongoblet epithelial cells and goblet cell density (GCD) in the pterygial area
      were calculated and compared over time across treatment groups. RESULTS:
      Pterygium excision wounds healed in a similar four-stage process in all groups,
      but at different rates and with different final results. The N/C ratio was
      highest at about 1 month postoperatively in groups 1 and 2 and at 2 weeks in
      group 3, before gradually returning to control levels. Preoperatively, the GCD in
      treated eyes was almost twice that in control eyes (p = 0.001) but fell to zero
      immediately postoperatively. Goblet cells first appeared (with the most rapidly
      increased density) in group 3, followed by group 1. At 12 months, the mean GCD in
      groups 1 and 3 were not significantly different from those in controls, whereas
      the mean GCD in group 2 was still less than that of control (p = 0.02).
      CONCLUSIONS: Healing of conjunctiva is delayed by MMC and is promoted by
      autografting. Even 1 year after surgery, the ocular surface remains abnormal with
      respect to epithelial phenotypes in eyes treated by any of the three techniques.

PMID- 11322411
TI  - Management of increased vitreous pressure during penetrating keratoplasty using
      pars plana anterior vitreous aspiration.
AB  - PURPOSE: To describe the technique, outcomes, and complication rates for a method
      of pars plana vitreous aspiration to control excessive vitreous pressure during
      penetrating keratoplasty. METHODS: All cases of penetrating keratoplasty were
      reviewed retrospectively in a large cornea subspecialty private practice over a 5
      year period, and 70 cases of penetrating keratoplasty complicated by excessive
      posterior pressure were identified. Study eyes were treated with a pars plana
      vitreous aspiration technique to relieve excessive posterior vitreous pressure.
      The main study parameters included preoperative best corrected visual acuity
      (BCVA), postoperative BCVA at the last recorded follow-up visit, refractive
      cylinder at 1 year, complications related to surgery, and other conditions that
      may have influenced visual function. The mean follow-up period was 24.5 months
      with a range of 1 to 61.1 months. RESULTS: Adverse outcomes during the extended
      period of follow-up included rejection in 11 of 70 eyes, graft failure in 7 of 70
      eyes, glaucoma in 4 of 70 eyes, and postoperative cystoid macular edema (CME) in
      5 of 70 eyes. Posterior capsulotomies using the neodymium-yttrium aluminum garnet
      laser were necessary in 10 of 70 patients during the follow-up period. The
      average magnitude of refractive astigmatism at 1 year after surgery was 3.73
      diopters (D) with a range of 0 to 8 D. There were no known retinal complications
      other than CME and no complications that could be directly attributed to the pars
      plana vitreous aspiration technique. CONCLUSIONS: Pars plana anterior vitreous
      aspiration is a safe and effective technique for controlling increased vitreous
      pressure, which can complicate penetrating keratoplasty.

PMID- 11322412
TI  - Quantitative evaluation of atopic blepharitis by scoring of eyelid conditions and
      measuring the water content of the skin and evaporation from the eyelid surface.
AB  - PURPOSE: To quantitatively evaluate the condition of the eyelid skin of patients
      with atopic blepharitis, their symptoms were scored and the water content of the
      skin and evaporation from the skin were measured. METHODS: Forty patients with
      atopic blepharitis were examined. The condition of eyelid skin (erythema,
      edema/papulation/oozing/crust, excoriation/lichenification) was scored from 0 to
      3 points. Water content and water evaporation were measured with a Moisture
      Checker and an evaporimeter, respectively. Eleven age-matched volunteers without
      atopic disorders were recruited as normal controls. RESULTS: The Moisture Checker
      values and water evaporation from lid skin were significantly correlated (r = 
      0.44, p = 0.006). The Moisture Checker values of the patients with atopic
      blepharitis was 35.5+/-8.2% (44.7 +/-10.6% in the normal controls, p = 0.009),
      and water evaporation from their lid skin was 3.6+/-0.9 g/cm2 per second (2.0+/
      0.3 g/cm2 per second, p < 0.001); then, the patients were divided into four
      groups, from "asymptomatic" to "severe," according to the sum of their
      blepharitis scores. Patients with lower blepharitis scores tended to have higher
      Moisture Checker values and lower water evaporation values. CONCLUSION: Scoring
      of eyelid condition enabled us to objectively estimate the severity of atopic
      blepharitis. Measurements of the water content of lid skin and water evaporation
      from lid skin are useful in evaluation of the severity of this disease.

PMID- 11322413
TI  - Bacterial contamination of human organ-cultured corneas.
AB  - PURPOSE: The aim of this study was to detect and identify bacterial contaminants
      in human corneoscleral tissue after organ culture storage. METHODS: Seventy-two
      corneoscleral rims and corneal buttons trephined from organ cultured
      corneoscleral discs using aseptic technique and 45 organ-cultured donor
      corneoscleral rims postpenetrating keratoplasty) were subjected to a mechanical
      extraction technique using a Stomacher laboratory blender. As a control, 28 of
      the corneoscleral rims and buttons were halved; one half of each corneoscleral
      rim and button was decontaminated in formalin for 48 hours before thorough
      washing in balanced salt solution. Corneal specimens, culture medium, and
      transport (5% dextran) medium were cultured in brain-heart infusion broth at 37
      degrees C for 5 days. Bacterial isolates were identified after culture of turbid
      enrichment broth. RESULTS: Bacterial contamination was demonstrated in 29% (21 of
      72) of the corneoscleral rims and 15% (11 of 72) of the corneal buttons that were
      trephined aseptically from corneoscleral discs and in 29% (13 of 45) of
      postkeratoplasty corneoscleral rims. Bacterial contaminants were not isolated
      from controls. Isolated microorganisms included coagulase-negative
      Staphylococcus, Staphylococcus aureus, Streptococcus viridans, Pseudomonas sp,
      and Bacillus sp. A correlation was not demonstrated between contamination and
      cause of death, death to enucleation, death to culture time, or time in culture.
      Postkeratoplasty endophthalmitis was not evident in the patients who had received
      corneal buttons from those corneoscleral discs that had contaminated
      corneoscleral rims. CONCLUSIONS: Bacterial contamination exists in corneoscleral
      tissue after organ culture storage. The difference in distribution of bacteria
      and percentage of contamination between the peripheral and central corneas causes
      us to question the value of routine postpenetrating keratoplasty corneoscleral
      rim cultures.

PMID- 11322414
TI  - The effect of long-term, daily contact lens wear on corneal sensitivity.
AB  - PURPOSE: To assess the effect of long-term, daily-wear soft contact lenses and
      rigid gas permeable (RGP) contact lenses on corneal sensitivity using a
      noninvasive, air-pulse stimulus. METHODS: The central and peripheral (temporal,
      medial, inferior) corneal sensation thresholds of 40 non-lens wearers, 40 soft
      lens wearers, and 40 RGP lens wearers were assessed using the Non-Contact Corneal
      Aesthesiometer (NCCA). The individuals who wore contact lenses were grouped
      according to the number of years of lens wear (10 years or less, 11-20 years, and
      21 years or more). RESULTS: Although a significant reduction in corneal
      sensitivity was found between the contact lens wearers and non-lens wearers (p =
      0.000), no difference was found between the two lens-type subgroups (p = 0.939).
      This pattern of significance was repeated at each of the peripheral test
      locations. No relationship between corneal sensitivity and years of lens wear was
      found centrally (r2 = 0.004) or at any of the peripheral test locations. No
      significant difference was found between the central corneal sensation thresholds
      for the different subgroups of lens wear duration (p = 0.469) or for any of the
      peripheral test locations. CONCLUSIONS: Both soft and RGP lens wear produce a
      similar type of corneal sensitivity loss, although the mechanism for this loss is
      different for the two lens types. The extent of sensitivity loss is not related
      to the duration of lens wear and appears to plateau after the first few months of
      wear. No topographical variation in sensitivity loss was found with lens type or
      with the duration of lens wear.

PMID- 11322415
TI  - Gender- and age-related differences in corneal topography.
AB  - PURPOSE: To investigate gender- and age-related differences in the corneal
      topography of a normal population. METHODS: One hundred thirty-two topographic
      examinations were collected from 100 patients ranging in age from 23 to 83 years
      (average, 57.35+/-17.38 years). Data were segregated by gender and further
      divided into younger (less than 50 years) and older (50 years or more) age
      groups. The topographic indices of Surface Regularity Index, Surface Asymmetry
      Index, Irregular Astigmatism Index, Standard Deviation of Corneal Power, Corneal
      Eccentricity Index, Coefficient of Variation of Corneal Power, Simulated
      Keratometry 1 and 2, and Average Corneal Power were examined. The astigmatism
      pattern and corneal irregularity were determined and compared with respect to
      gender and age. RESULTS: The corneas of older men were flatter than those of
      older women (p < 0.001). The vertical corneal meridian, but not the horizontal
      meridian, showed statistically significant gender-related changes with aging (p <
      0.001). Older men had a significantly higher potential for against-the-rule
      astigmatism than women (p < 0.001). Corneal irregularity (measured in terms of
      the Surface Regularity Index and Irregular Astigmatism Index) increased with age
      (p < 0.001 and p < 0.001, respectively), although there was no gender-related
      difference. In the younger group, no gender-related differences in corneal
      curvature or astigmatism pattern were found. CONCLUSION: Aging influences changes
      in patterns of astigmatism differently in men and women. Decreases in levels of
      sex hormones may play a role in gender-related changes in corneal structure with
      age.

PMID- 11322416
TI  - Human immunodeficiency virus p24 antigen testing in cornea donors.
AB  - PURPOSE: Testing for the p24 antigen of the human immunodeficiency virus (HIV)
      may detect early HIV infection in the seronegative window; however, falsely
      reactive results may occur in cadaver specimens. Although neither the Food and
      Drug Administration (FDA) nor the Eye Bank Association of America requires p24
      testing of cornea donors, many tissue banks using other organs from cornea donors
      do perform this assay, and the FDA requires that eye banks reject corneal tissue
      if a reactive p24 assay is reported. We investigated the impact of p24 testing on
      eye banking and corneal transplantation. METHODS: Two clinical cases and records
      from the Lions Eye Bank of Delaware Valley (LEBDV) were reviewed retrospectively.
      RESULTS: Two corneas from the LEBDV were transplanted before the reporting of p24
      reactivity by other tissue banks. In one case, because of the young age of the
      recipient, the surgeon elected to replace the cornea with new tissue hours after
      the original transplant, and later polymerase chain reaction (PCR) testing was
      negative. In the other case, there was not enough specimen to perform Western
      blot or PCR confirmatory testing. The patient was followed with periodic
      serologic testing for HIV and has remained seronegative. To avoid such problems
      in the future, the LEBDV initiated testing of all donors with p24 and other
      nonrequired screening tests. Over a 2-month period, 22 corneas (from 11 donors)
      were discarded because of these tests: 4 donors had reactive p24 tests, 6 were
      reactive for antibody to hepatitis B core antigen, and 1 had a reactive syphilis
      test. CONCLUSIONS: Results from p24 assays by other tissue banks may cause
      difficult clinical situations when the results are received after transplantation
      of the tissue, but the use of the p24 assay in the screening of cornea donors may
      result in excessive waste of donor tissue. Further guidance is needed regarding
      the management of positive results from this and other nonrequired screening
      tests.

PMID- 11322417
TI  - Optical coherence tomography for the noninvasive evaluation of the cornea.
AB  - PURPOSE: To determine the optical coherence tomographic (OCT) characteristics of
      normal corneas and to characterize the OCT images of abnormal corneal lesions.
      METHODS: Eleven eyes from 10 patients were examined at the Cornea Service of the
      Nagoya University Hospital: 4 had corneal pathologies, 4 underwent keratoplasty,
      and 2 were normal controls; 1 enucleated eye was also examined. OCT (OCT 2000
      Zeiss-Humphrey) was used to study the normal cornea and various corneal
      abnormalities. We compared the OCT images to the observations made by slit-lamp
      biomicroscopy. RESULTS: Fluid spaces were detected as black images. A highly
      reflective reflex was observed at the interface of different tissues, and
      intensive backscattering (reflex) was seen when the incident ray hit the
      laminated layers vertically. Corneal opacities were not clearly imaged when they
      were diffuse and mild, or when they were arranged axially in a small area, as was
      the scar of the graft-host junction. It was possible to obtain images from the
      region of the cornea that was not clearly visible by slit-lamp examination
      because of a corneal opacity. CONCLUSION: OCT is a noncontact and noninvasive
      technique that can be performed safely on diseased corneas. OCT can provide
      objective documentation of corneal disorders that cannot be obtained by slit-lamp
      examination. The use of OCT in conjunction with other conventional instruments
      should provide a more complete image of the cornea.

PMID- 11322418
TI  - Trends in contact lens-related corneal ulcers.
AB  - PURPOSE: To identify changes in number of contact lens-related corneal ulcers per
      year and the type of contact lenses involved. METHODS: Charts of 299 patients
      with corneal ulcers seen at the Cornea Service of Wills Eye Hospital from January
      1, 1996, to June 30, 1999, were retrospectively reviewed. A corneal ulcer was
      defined as an infiltrate that was treated at least hourly with topical fortified
      antibiotics or fluoroquinolones. RESULTS: Of these 299 cases, 37 (12.4%) were
      related to contact lens use. Contact lens-related ulcers accounted for 10.7% of
      all corneal ulcers in 1996, 15.3% in 1997, 8.6% in 1998, and 18.2% in the first 6
      months of 1999. The contact lenses most commonly associated with ulcers were
      conventional soft daily-wear contact lenses (33%). There were similar numbers of
      ulcers associated with extended wear (n = 16) and daily wear (n = 17) of soft
      contact lenses. In addition, the number of cases associated with conventional (n
      = 17) and disposable/frequent replacement (n = 16) lenses were similar. Corneal
      cultures were performed in 15 (40.5%) cases and were positive in 8. There has
      been a significant decrease in the number of contact lens-related ulcers treated
      at our institution compared with previous years (1988-1999, p < 0.01).
      CONCLUSIONS: The number of contact lens-related corneal ulcers in the past 4
      years was significantly fewer than previous years at our institution. A similar
      number of ulcers were associated with conventional and disposable/frequent
      replacement lenses despite the commercial preponderance of the latter type of
      lenses.

PMID- 11322419
TI  - Hemorrhagic viral keratoconjunctivitis in Taiwan caused by adenovirus types 19
      and 37: applicability of polymerase chain reaction-restriction fragment length
      polymorphism in detecting adenovirus genotypes.
AB  - PURPOSE: Acute keratoconjunctivitis with prominent subconjunctival hemorrhage
      (SCH) is usually perceived by a clinician as acute hemorrhagic conjunctivitis
      (AHC) associated with enteroviruses; however, SCH can also be an adenoviruses
      infection. A rapid and sensitive laboratory diagnosis is helpful for differential
      diagnosis. Therefore, the sensitivity and applicability of polymerase chain
      reaction (PCR) and reverse transcription (RT)-PCR diagnoses were evaluated for
      keratoconjunctivitis associated with viral infection. METHODS: Conjunctival swabs
      from patients with acute conjunctivitis were tested using a PCR-restriction
      fragment length polymorphism (PCR-RFLP) for adenovirus detection and RT-PCR for
      enterovirus detection. The results were compared with those using the culture
      isolation and neutralization test; also, the clinical findings of the patients
      were analyzed with special attention to SCH patterns. RESULTS: Neither
      coxsackievirus A type 24 variant (CA24v) nor enterovirus type 70 (EV70) was
      detected in 113 patients with acute conjunctivitis. The positive results of
      adenovirus (Ad) were 39.9% by the PCR method and 37.1% by culture isolation. For
      the patients with adenoviral conjunctivitis, 68.1% was owing to Ad37 and 19.2%
      was owing to Ad19. SCH was present in 51.5% of the positive cases, and 44.7% of
      the Ad-positive patients had secondary illnesses. CONCLUSIONS: SCH can be a
      predominant presentation of Ad19 and Ad37 keratoconjunctivitis and may herald a
      new stage in the evolution of adenoviruses. PCR and PCR-RFLP are rapid and
      reliable methods for Ad detection and typing; however, if the amplified genes and
      restriction enzymes are not properly selected, they may not be able to detect new
      genotypes of adenoviruses or the evolution of these viruses.

PMID- 11322420
TI  - In vitro susceptibilities of bacterial ocular isolates to fluoroquinolones.
AB  - PURPOSE: To evaluate and compare the in vitro antimicrobial activity of
      levofloxacin versus ciprofloxacin and ofloxacin against ocular isolates from
      patients with bacterial conjunctivitis. METHODS: The in vitro antimicrobial
      susceptibilities of ocular isolates to levofloxacin, ofloxacin, and ciprofloxacin
      were determined using both the agar disk diffusion and broth dilution methods.
      RESULTS: Disk diffusion susceptibility testing disclosed that 99% (100 of 101
      isolates) of gram-negative isolates and 98% (127 of 129 isolates) of gram
      positive isolates were susceptible to levofloxacin; 96% (97 of 101 isolates) of
      gram-negative isolates and 78% (100 of 129 isolates) of gram-positive isolates
      were susceptible to ofloxacin; and 94% (95 of 101 isolates) of gram-negative
      isolates and 61% (79 of 129 isolates) of gram-positive isolates were susceptible
      to ciprofloxacin. Broth dilution testing disclosed that 99% (72 of 73 isolates)
      of gram-negative isolates and 98% (111 of 113 isolates) of gram-positive isolates
      were susceptible to levofloxacin; 96% (70 of 73 isolates) of gram-negative
      isolates and 92% (104 of 113 isolates) of gram-positive isolates were susceptible
      to ofloxacin; and 95% (69 of 73 isolates) of gram-negative isolates and 82% (93
      of 113 isolates) of gram-positive isolates were susceptible to ciprofloxacin.
      CONCLUSIONS: In this study, levofloxacin demonstrated superior in vitro activity
      against human bacterial conjunctival isolates compared with either ofloxacin or
      ciprofloxacin (levofloxacin > ofloxacin > ciprofloxacin).

PMID- 11322421
TI  - Lomefloxacin is an effective treatment of experimental bacterial keratitis.
AB  - PURPOSE: Lomefloxacin was evaluated as a potential topical therapy for bacterial
      keratitis. METHODS: Lomefloxacin was compared with ciprofloxacin in different
      rabbit keratitis models. A total of 216 corneas were infected with Staphylococcus
      aureus (ciprofloxacin-susceptible and -resistant), Streptococcus viridans,
      Streptococcus pneumoniae, Pseudomonas aeruginosa, and Serratia marcescens and
      were treated with lomefloxacin (0.3%), ciprofloxacin (0.3% Ciloxan), and the
      control phosphate-buffered saline (PBS), respectively. The data were analyzed
      statistically comparing the decrease in the number of recovered viable bacteria.
      RESULTS: Compared with PBS-treated control corneas, the colony counts for all
      bacterial isolates were significantly reduced (p < 0.05) after topical treatment
      with either lomefloxacin or ciprofloxacin. For gram-positive bacteria,
      lomefloxacin and ciprofloxacin were equally effective. For gram-negative
      bacteria, lomefloxacin, while effective, was less so than ciprofloxacin under
      experimental conditions (p < 0.05). CONCLUSION: Our data, using multiple
      bacterial keratitis models, suggest that lomefloxacin is promising for therapy of
      bacterial keratitis. Further clinical studies are needed to expand its use for
      keratitis therapy.

PMID- 11322422
TI  - Identification of cell types in human diseased corneas.
AB  - PURPOSE: Activated myofibroblasts and macrophages are often found in corneal
      wound models. The current study was performed to determine whether human diseased
      corneas that had active tissue remodeling and enzyme activities also possessed
      myofibroblasts, macrophages, major histocompatibility complex class II cells,
      and/or CD-68-positive cells. METHODS: Normal, keratoconus, keratoconus with
      hydrops, bullous keratopathy, map-dot-fingerprint dystrophy, failed grafts, and
      acid burn/neovascularized corneas were collected, frozen in OCT, sectioned, and
      stained with antibodies to alpha smooth muscle actin (myofibroblast marker), CD14
      (macrophage marker), CD68 (lysosomal membrane marker), and HLA-DR (major
      histocompatibility complex class II cells). Selective histochemical stains
      identified lysosomal enzymes. RESULTS: Normal and map-dot-fingerprint dystrophy
      corneas lacked antibody and enzyme staining. Keratoconus corneas were positive
      for CD68, HLA-DR, and lysosomal enzymes but were negative for CD14 and smooth
      muscle actin. Bullous keratopathy corneas had CD68-, CD14-, and HLA-DR-positive
      cells, relatively normal enzyme levels, and were smooth muscle actin-negative.
      Failed graft corneas had significant numbers of CD68-, CD14-, and HLA-DR-positive
      cells and increased acid phosphatase, but these corneas were smooth muscle actin
      negative. Ulcerated and vascularized corneas had positive staining with all
      antibodies that were examined. Cultured stromal cells from normal corneas were
      CD68-positive, CD14-negative, and alpha smooth muscle actin-negative, and they
      produced lysosomal enzymes. CONCLUSIONS: The current study demonstrates that
      increased presence of lysosomal enzymes, corneal remodeling, and fibrosis can
      occur in the absence of myofibroblasts and/or macrophages.

PMID- 11322423
TI  - Corneal preparation of eye bank eyes for experimental surgery.
AB  - PURPOSE: To evaluate the efficacy of dextran in balanced salt solution (BSS) as a
      preparation of eye bank corneas for experimental surgeries. METHODS: We used 12
      eye bank eyes that were unsuitable for transplant. The corneas were removed from
      the globe and affixed to a Hanna artificial anterior chamber. Four concentrations
      of dextran-BSS (10%, 15%, 20%, and 30% [+/-0.56%]) were used to dehydrate the
      corneas, and corneal thickness was assessed with an ultrasonic pachymeter (+/-5
      microm) at varying time-intervals over 3 hours. RESULTS: The corneas were thinned
      to an average thickness of 477+/-54 microm, 430+/-54 microm, 406+/-61 microm, and
      391+/-52 microm at average times of 75+/-0 minutes, 85+/-23 minutes, 60+/-12
      minutes, and 45+/-0 minutes for the 10%, 15%, 20%, and 30% concentrations,
      respectively. Corneal thickness was stabilized in both a 15% and a 20% solution.
      The data was fit to exponential curves until a minimum value was reached, after
      which linear regression analysis was used to determine the slopes of the data.
      The slopes for the 15% and 20% concentrations were not significantly different
      from 0 (p = 0.5 and p = 0.4, respectively). The slopes for each set of data from
      the 10% and 30% concentrations were significantly different from each other (p =
      0.010 and p = 0.001, respectively). CONCLUSIONS: A solution of 20% dextran in BSS
      is effective for dehydrating eye bank corneas to a quasi-normal physiologic
      thickness and for maintaining the thickness for a sufficient amount of time. Both
      the posterior and anterior sides of the cornea should be exposed to the solution
      for 60 minutes.

PMID- 11322424
TI  - Short-term impact of corticosteroids on hyaluronan and epithelial hyperplasia in
      the rabbit cornea after photorefractive keratectomy.
AB  - PURPOSE: To investigate the impact of corticosteroids on subepithelial hyaluronan
      deposition and corneal epithelium thickness in the first 10 days after
      photorefractive keratectomy (PRK) and to analyze a possible contralateral effect
      of corticosteroids. METHODS: Thirty-two New Zealand white rabbits were assigned
      into two groups and had a transepithelial 5.0-mm diameter, 8.00-diopter myopic
      PRK performed on one eye. The corticosteroid treatment group (16 animals)
      received 0.1 mL of methylprednisolone 4% subconjunctivally on the operation
      table, followed by 0.1% dexamethasone eye drops six times a day during the
      postoperative period. The sodium chloride (NaCl) treatment group received topical
      isotonic NaCl eye drops six times a day. In each treatment group, eight animals
      were killed after 3 and 9 days, respectively. The harvested specimens were
      stained for hyaluronan and the epithelial thickness was measured. RESULTS: In
      contrast to the epithelial thickness, the subepithelial hyaluronan did not show a
      significant increase during the observation period. The corticosteroid treated
      group showed at both time-points significantly less subepithelial hyaluronan
      formation as well as a significantly thinner epithelium, when compared with the
      NaCl-treated group. At 9 days, the corticosteroid-treated group showed a mild
      epithelial hyperplasia in only one of eight eyes, whereas this was a common
      finding in the NaCl-treated group. We detected no hyaluronan deposits in any
      contralateral-untreated eye, and the epithelial thickness did not differ
      significantly between any of the four contralateral-untreated eye groups.
      CONCLUSIONS: Corticosteroid medication during the first 10 days after operation
      reduces the amount of subepithelial hyaluronan production and inhibits the
      epithelial proliferation, and epithelial hyperplasia is prevented. Neither a
      contralateral hyaluronan deposition nor a contralateral corticosteroid effect
      could be detected.

PMID- 11322425
TI  - Experimental study using pig eyes for realizing ideal astigmatic keratotomy.
AB  - PURPOSE: The effects of varying the incision length and depth were analyzed using
      pig eyes to acquire information for realizing an ideal method of astigmatic
      keratotomy (AK). METHODS: Single and paired arcuate incisions were made on pig
      corneas using a diamond knife. Incisions with varying lengths of 40 degrees, 60
      degrees, and 90 degrees were made with the incision depth fixed at 90% of corneal
      thickness. Next, paired incisions with varying incision depth from 20% to 95% of
      corneal thickness were made with the incision length fixed at 90 degrees. The
      changes in corneal shape were analyzed using corneal topography and the degrees
      of astigmatic change were measured using a surgical keratometer. RESULTS: For
      short single and paired incisions (40 degrees or 60 degrees in length), narrow
      areas of flattenings occurred, and steepenings were observed on both sides
      adjacent to the flattened areas. For long paired incisions of 90 degrees length,
      wide areas of flattenings and steepenings were observed with an approximately 1:1
      coupling ratio, and a positive linear relationship between the incision depth and
      degree of astigmatic change was observed in the range of incision depth between
      40% and 80% of corneal thickness. CONCLUSION: This experimental study suggests
      that for achieving ideal corneal sphericity after AK, long incisions covering the
      entire steep areas (paired 90 degrees incisions for regular astigmatism) should
      be used and the degree of astigmatic correction may be controlled by varying the
      incision depth.

PMID- 11322426
TI  - Autoimmune keratolysis in a patient with leukocytoclastic vasculitis: unusual
      erythema elevatum diutinum with granulomatous pattern.
AB  - PURPOSE: Leukocytoclastic vasculitis (LCCV) is an immune complex-mediated, small
      vessel disease that is clinically characterized by the presence of palpable
      purpuric lesions, most often in association with rheumatic diseases. Ocular
      manifestations of LCCV are rare. METHODS: We describe a patient with an unusual
      granulomatous pattern of erythema elevatum diutinum (EED) associated with
      autoimmune keratolysis. RESULTS: We studied a 64-year-old man with decreased
      visual acuity and nodular lesions in both hands. Ocular examination revealed
      bilateral superior corneal melting with perforation in the left eye and
      conjunctival thickening in both eyes, in association with a severe inflammatory
      reaction. Histopathologic examination of the conjunctiva revealed granulomatous
      vasculitis with neutrophilic infiltrate, giant cells, and fibroblastic
      proliferation. A punch biopsy taken from his skin showed similar characteristics
      that suggested EED; however, there were no giant cells. CONCLUSION: To our
      knowledge, autoimmune keratolysis secondary to cutaneous LCCV (EED) has not been
      described previously, and there has been no description of granulomatous reaction
      (in the conjunctiva) in EED.

PMID- 11322427
TI  - Findings in the anterior segment on ultrasound biomicroscopy in Maroteaux-Lamy
      syndrome.
AB  - PURPOSE: Maroteaux-Lamy syndrome is one of the mucopolysaccharidoses caused by
      enzyme deficiency (arylsulfatase B) that leads to incomplete degradation and
      storage of dermatan sulfate. We report a case of mucopolysaccharidosis type VI
      (MPS VI; Maroteaux-Lamy syndrome) with corneal involvement and introduce
      ultrasound biomicroscopy (UBM) as an examination with which to follow disease
      progression in relation to deposition in cornea, angle, and iris. METHODS: We
      describe a 11-year-old boy with a clinical and laboratorial diagnosis of MPS VI
      who developed increasing bilateral corneal opacification and decreased visual
      acuity. He underwent two seriate UBM (50-MHz transducer) evaluations. RESULTS:
      UBM examination showed diffuse and homogeneous stromal hyper-reflective deposit
      in both eyes and an increase in peripheral corneal thickness throughout time.
      CONCLUSION: High-frequency ultrasound documentation of corneal deposit and
      anterior segment involvement in a patient with Maroteaux-Lamy syndrome is unique,
      and follow-up revealed thickening of the corneal periphery, which may be related
      to the progression of the disease (continuous mucopolysaccharide deposits in
      corneal stroma). UBM was used to locate and document the deposit, as well as to
      accompany the deposit's evolution, characterizing corneal changes and angle
      structure involvement.

PMID- 11322428
TI  - Flap haze after epithelial debridement and flap hydration for treatment of post
      laser in situ keratomileusis striae.
AB  - PURPOSE: To report a case of corneal haze after attempts to eliminate post-laser
      in situ keratomileusis (LASIK) lamellar striae. METHODS: Case report. RESULTS: A
      24-year-old woman with visually significant flap striae 2 months after LASIK
      underwent manual epithelial debridement and flap hydration, refloating, and
      stretching to eliminate the striae. Three weeks after this intervention, she
      developed visually significant haze that was confined to the stroma of the flap.
      The haze slowly improved with use of a topical steroid. CONCLUSION: Stromal haze
      can develop after treatment of flap striae with epithelial debridement and hypo
      osmolar irrigation. We speculate that these maneuvers may have induced cell death
      of anterior keratocytes and led to haze formation, as can occur after simple
      epithelial debridement and epithelial scrape-photorefractive keratectomy.

PMID- 11322429
TI  - Aspergillus fumigatus keratitis after laser in situ keratomileusis.
AB  - PURPOSE: To report a case of Aspergillus fumigatus keratitis after a laser in
      situ keratomileusis (LASIK) enhancement procedure. METHOD: Case report. RESULTS:
      A 56-year-old woman developed an ulcer in the flap 13 days after LASIK
      enhancement. A 4-week course of fortified antibiotics for a presumed bacterial
      infection followed. The ulcer progressed, causing 60% thinning of the corneal
      stroma. A biopsy was performed 5 weeks after onset of symptoms, and antifungal
      agents were initiated. Cultures showed A. fumigatus. Her cornea perforated after
      the biopsy, requiring cyanoacrylate and lamellar overlay sutures, but the
      infiltrate resolved on antifungal agents. CONCLUSION: This report is the first
      description of Aspergillus keratitis after LASIK. We hypothesize that the
      infection became established on the stromal bed during surgery and led to
      melting, anteriorly through the flap and posteriorly through the stroma.
      Diagnosis was made by a corneal biopsy and inoculation of a wide array of media.
      This case demonstrates the need to consider atypical organisms, including fungi,
      in the differential diagnosis of post-LASIK infections when there is no response
      to therapy and highlights the role of corneal biopsy and flap lifting in the
      diagnosis of this condition.

PMID- 11322430
TI  - What factors are related to impairment of cerebrovascular reserve before and
      after arteriovenous malformation resection? A cerebral blood flow study using
      xenon-enhanced computed tomography.
AB  - OBJECTIVE: To examine the incidence and possible determinants of impaired
      vascular reserve in arteriovenous malformation (AVM)-affected brain, before and
      after surgery. METHODS: In a prospective study of 30 patients, the regional
      cerebrovascular reserve capacity (rCRC) and the vasodilated regional cerebral
      blood flow (rCBF) were assessed during an acetazolamide challenge, using xenon
      enhanced computed tomography, before and after complete AVM resection. Single
      brain slices at the level of the basal ganglia were examined, and scanning
      through the AVMs was avoided. Five regions of interest in the AVM-bearing
      hemisphere were compared with their counterparts in the unaffected hemisphere.
      Vasodilated rCBF reductions of at least 20% in one or more regions of interest
      and rCRC values of less than 10 ml/100 g/min were considered to be significant.
      RESULTS: Ipsilateral vasodilated rCBF was significantly reduced in 17 patients
      before surgery and 15 patients after surgery. Ipsilateral rCRC was impaired in 14
      patients before surgery and 12 patients after surgery. Large AVM size, venous
      congestion, and AVM-related vascular territories were correlated with impaired
      vascular reserve in AVM-nonadjacent brain tissue before surgery. Similar
      correlations were observed after surgery, except that not AVM size but a large
      number of AVM-supplying vascular territories was correlated. Moreover, the
      smallest AVMs and those supplied by a single vascular territory, as well as
      hemorrhage and nonhemorrhagic neurological deficits as presenting symptoms, were
      correlated with reduced ipsilateral vasodilated rCBF before surgery. Among
      patients with AVMs and nonhemorrhagic epilepsy, a trend of impaired
      cerebrovascular reserve was observed. In the only case of postresectional
      "breakthrough," the preoperative rCRC was not impaired but abnormally high.
      CONCLUSION: Among the determinants of impaired cerebrovascular reserve, AVM size
      is already a constituent of current grading scales and decision-making paradigms,
      whereas factors such as venous congestion have been less closely considered or
      less obvious but may deserve increased attention in the future. Nonhemorrhagic
      epilepsy in patients with AVMs may constitute the clinical equivalent of chronic
      cerebral ischemia in a murine model. Postresectional breakthrough may be partly
      attributable to individual predisposition to excessive vasoreactivity in the
      whole brain.

PMID- 11322431
TI  - Elevation of soluble intercellular adhesion molecule-1 levels in symptomatic and
      asymptomatic carotid atherosclerosis.
AB  - OBJECTIVE: Recent data suggest that the increased expression of intercellular
      adhesion molecule-1 (ICAM-1) in atherosclerotic plaque taken from the carotid
      bifurcation correlates with the development of neurological symptoms. As a
      result, the authors sought to compare the serum levels of soluble forms of ICAM-1
      (sICAM-1) in patients who were asymptomatic with those who were symptomatic for
      carotid artery stenosis as well as in patients who were matched in terms of sex,
      age, and risk factors who did not have carotid artery disease. METHODS: Using
      enzyme-linked immunosorbent assay, serum sICAM-1 levels were prospectively
      determined in 54 patients scheduled to undergo carotid endarterectomy for either
      symptomatic or asymptomatic high-grade stenosis (> or =60%) and in 5 additional
      patient controls. Data are expressed as mean +/- standard error of the mean, with
      significance defined as P < 0.05 using the Mann-Whitney two-tailed test for two
      column comparison or analysis of variance and Fisher protected least significant
      difference test. RESULTS: Using a univariate model, serum sICAM-1 levels were
      significantly elevated in patients with carotid artery stenosis as compared with
      control patients without stenosis (347 +/- 15 ng/ml versus 216 +/- 8.2 ng/ml) (P
      < 0.01). When the asymptomatic and symptomatic patients with carotid artery
      stenosis were considered separately, these levels were still elevated relative to
      those of control patients (asymptomatic [312 +/- 18 ng/ml] and symptomatic [376
      +/- 22 ng/ml] patients; P = 0.06 for asymptomatic versus control patients, P <
      0.01 for symptomatic versus control patients). Symptomatic patients also had
      significantly elevated sICAM-1 levels as compared with asymptomatic patients (P <
      0.05). Despite the fact that female patients demonstrated higher ICAM-1 levels
      than male patients (P < 0.05), sex, age, and risk factors such as the presence of
      hypercholesterolemia, diabetes, hypertension, or a history of smoking did not
      confound these findings. CONCLUSION: Levels of sICAM-1 are higher in patients
      with carotid stenosis than in control patients. Symptomatic patients demonstrate
      significantly elevated levels as compared with asymptomatic patients. These data
      support the contention that ICAM-1 is a reliable marker of carotid disease
      progression and suggest that serum levels may be useful in following certain
      asymptomatic patients.

PMID- 11322432
TI  - Milrinone for the treatment of cerebral vasospasm after subarachnoid hemorrhage:
      report of seven cases.
AB  - OBJECTIVE: The intra-arterial infusion of papaverine has been used for dilation
      of spastic cerebral vessels after aneurysmal subarachnoid hemorrhage, although
      its efficacy is controversial. Milrinone is an inotropic drug that dilates
      vessels by phosphodiesterase inhibition in a mechanism similar to that of
      papaverine. We examined the effects of intra-arterial and subsequent intravenous
      administration of milrinone on patients with symptomatic cerebral vasospasm.
      METHODS: Seven patients with cerebral vasospasm were enrolled in this study.
      Milrinone was delivered intra-arterially via catheter at a rate of 0.25 mg/min.
      The total delivered dose was between 2.5 and 15 mg. Radiological measurement of
      the middle cerebral artery diameter and cerebral blood flow was carried out
      before and after arterial infusion. Intravenous treatment followed at 0.50 or
      0.75 microg/kg/min for up to 2 weeks from the onset of subarachnoid hemorrhage.
      RESULTS: Dilation of the vasospastic vessels occurred in all patients. The rate
      of cerebral blood flow was calculated in six patients and was increased in all.
      Subsequent intravenous infusion was effective in preventing a recurrence of
      symptomatic vasospasm in four of the seven patients. CONCLUSION: It is suggested
      that milrinone was effective and safe for the treatment of cerebral vasospasm
      after subarachnoid hemorrhage in the patients in this series. Intra-arterial
      infusion with adjunctive intravenous infusion holds promise as a clinically
      advantageous treatment regimen.

PMID- 11322433
TI  - Glioma resection in a shared-resource magnetic resonance operating room after
      optimal image-guided frameless stereotactic resection.
AB  - OBJECTIVE: We describe a shared-resource intraoperative magnetic resonance
      imaging (MRI) design that allocates time for both surgical procedures and routine
      diagnostic imaging. We investigated the safety and efficacy of this design as
      applied to the detection of residual glioma immediately after an optimal image
      guided frameless stereotactic resection (IGFSR). METHODS: Based on the twin
      operating rooms (ORs) concept, we installed a commercially available Hitachi
      AIRIS II, 0.3-tesla, vertical field, open MRI unit in its own specially designed
      OR (designated the magnetic resonance OR) immediately adjacent to a conventional
      neurosurgical OR. Between May 1998 and October 1999, this facility was used for
      both routine diagnostic imaging (969 diagnostic scans) and surgical procedures
      (50 craniotomies for tumor resection, 27 transsphenoidal explorations, and 5
      biopsies). Our study group, from which prospective data were collected, consisted
      of 40 of these patients who had glioma (World Health Organization Grades II-IV).
      These 40 patients first underwent optimal IGFSRs in the adjacent conventional OR,
      where resection continued until the surgeon believed that all of the accessible
      tumor had been removed. Patients were then transferred to the magnetic resonance
      OR to check the completeness of the resection. If accessible residual tumor was
      observed, then a biopsy and an additional resection were performed. To validate
      intraoperative MRI findings, early postoperative MRI using a 1.5-tesla magnet was
      performed. RESULTS: Intraoperative images that were suitable for interpretation
      were obtained for all 40 patients after optimal IGFSRs. In 19 patients (47%),
      intraoperative MRI studies confirmed that adequate resection had been achieved
      after IGFSR alone. Intraoperative MRI studies showed accessible residual tumors
      in the remaining 21 patients (53%), all of whom underwent additional resections.
      Early postoperative MRI studies were obtained in 39 patients, confirming that the
      desired final extent of resection had been achieved in all of these patients. One
      patient developed a superficial wound infection, and no hazardous equipment or
      instrumentation problems occurred. CONCLUSION: Use of an intraoperative MRI
      facility that permits both diagnostic imaging and surgical procedures is safe and
      may represent a more cost-effective approach than dedicated intraoperative units
      for some hospital centers. Although we clearly demonstrate an improvement in
      volumetric glioma resection as compared with IGFSR alone, further study is
      required to determine the impact of this approach on patient survival.

PMID- 11322434
TI  - Surgical resection of calvarial metastases overlying dural sinuses.
AB  - OBJECTIVE: Few reports have addressed the surgical management of cranial
      metastases that overlie or invade the dural venous sinuses. To examine the role
      of surgery in the treatment of dural sinus calvarial metastases, we reviewed
      retrospectively 13 patients who were treated with surgery at the University of
      Texas M.D. Anderson Cancer Center between 1993 and 1999. We compared them with 14
      patients who had calvarial metastases that did not involve a venous sinus.
      METHODS: Clinical charts, radiological studies, pathological findings, and
      operative reports were analyzed retrospectively. RESULTS: The median age of
      patients with dural sinus calvarial metastases was 54 years. Nine patients were
      men and four were women. Renal cell carcinoma and sarcoma were the most common
      primary tumors. Similar features were noted in the 14 patients with nonsinus
      calvarial metastases. Of the 13 dural sinus calvarial metastases, 11 involved the
      superior sagittal sinus, and 2 involved the transverse sinus. In nine patients,
      the involved sinus was resected, and in four patients, the sinus was
      reconstituted after tumor removal. Nine patients in the dural sinus calvarial
      metastases group received en bloc resection, and four received piecemeal
      resection. No operative deaths occurred. The overall median actuarial survival
      was 16.5 months. The survival times of the two groups were comparable. In the
      group with dural sinus calvarial metastases, transient postoperative neurological
      deficits occurred in two patients (15%), and a permanent deficit occurred in one
      patient (8%). No patients in the group with nonsinus calvarial metastases
      experienced deficits after resection. Compared with piecemeal resection, en bloc
      resection was associated with significantly less blood loss. CONCLUSION: Complete
      extirpation of calvarial metastases that overlie or invade a dural sinus can be
      achieved with only slightly more morbidity than complete removal of calvarial
      metastases that are located away from the sinuses. En bloc resection is as safe
      as piecemeal resection and is more effective in limiting operative blood loss.
      The overall recurrence and survival rates of patients with dural sinus calvarial
      metastases are similar to those of patients with calvarial metastases that do not
      involve the sinuses. Therefore, involvement of a dural venous sinus should not
      discourage resection of calvarial metastases. In carefully selected cancer
      patients, surgery provides effective palliation of symptomatic calvarial
      metastases that overlie or invade the venous sinuses.

PMID- 11322435
TI  - Meningeal hemangiopericytoma: a retrospective study of 21 patients with special
      review of postoperative external radiotherapy.
AB  - OBJECTIVE: To specify that postoperative radiotherapy is useful for preventing
      local recurrence and neuraxis recurrence of surgically treated meningeal
      hemangiopericytomas. METHODS: We retrospectively studied 21 patients with
      meningeal hemangiopericytoma who were followed in our department during a 34-year
      period. In 17 patients, the meningeal hemangiopericytoma was intracranial, and in
      4 there was an intradural extramedullary localization. These groups were studied
      separately. RESULTS: Of the 17 patients with intracranial hemangiopericytoma, all
      underwent surgery; 8 also underwent radiotherapy (5,000-6,400 rads) (Group I),
      and 9 did not (Group II). The mortality rate was zero for Group I patients and
      55% for Group II. The mean local recurrence rate was 52% (12.5% in Group I and
      88% in Group II; P < 0.05). Neuraxis recurrences occurred in two patients in
      Group II, and none occurred in Group I (P = 0.4). Peripheral metastasis took
      place in two patients (22%) in Group II and in one patient (12.5%) in Group I (P
      = 0.5). Of the four patients with intradural extramedullary hemangiopericytoma,
      all underwent surgery. Two patients received 4000 rads of radiotherapy after
      intervention. No patient in this group had a recurrence. CONCLUSION: For patients
      with intracranial meningeal hemangiopericytoma, surgical removal followed by
      external radiotherapy reduced the risk of local recurrence. It was not
      demonstrated that postoperative radiotherapy protected against neuraxis
      metastasis. Radiotherapy did not protect against peripheral metastasis, which can
      occur up to several years after the first operation. It appears that radiotherapy
      after surgery for local or neuraxis recurrence did not avoid further recurrence.
      Radiosurgery is indicated for recurrent tumors measuring less than 25 mm in
      greatest diameter. For intradural extramedullary localizations, the value of
      postoperative radiotherapy is more questionable.

PMID- 11322436
TI  - Slit-ventricle syndrome secondary to shunt-induced suture ossification.
AB  - OBJECTIVE: To report five children with slit-ventricle syndrome who were found to
      have increased intracranial pressure despite functioning cerebrospinal fluid
      shunts. METHODS: Computed tomographic scans demonstrated erosion of the inner
      table of the cranium and sclerosis of the cranial sutures, particularly the
      coronal suture. Magnetic resonance imaging scans demonstrated no cerebrospinal
      fluid over the convexities. The patients were treated with cranial expansion
      operations that included removal of the sclerotic sutures, which were examined
      histologically. RESULTS: Postoperatively, symptoms resolved for all children.
      Sutures were abnormal and contained foci of cartilage and bone within abnormally
      arranged fibrous tissue. CONCLUSION: We postulate that chronic overdrainage of
      cerebrospinal fluid via shunts dampens the normal cerebral pressure waves; growth
      of the calvarium is thus understimulated, and this leads to ossification of the
      sutures, which become unable to expand to allow normal brain growth. Shunt
      induced craniostenosis should be considered for children with symptoms of slit
      ventricle syndrome for whom shunts are functional but intracranial pressure is
      increased. Cranial expansion operations may be more appropriate treatments than
      subtemporal decompressions for such children, given the diffuseness of the suture
      pathological features.

PMID- 11322437
TI  - Stereotactic navigation for placement of pedicle screws in the thoracic spine.
AB  - OBJECTIVE: Pedicle screw fixation in the lumbar spine has become the standard of
      care for various causes of spinal instability. However, because of the smaller
      size and more complex morphology of the thoracic pedicle, screw placement in the
      thoracic spine can be extremely challenging. In several published series,
      cortical violations have been reported in up to 50% of screws placed with
      standard fluoroscopic techniques. The goal of this study is to evaluate the
      accuracy of thoracic pedicle screw placement by use of image-guided techniques.
      METHODS: During the past 4 years, 266 image-guided thoracic pedicle screws were
      placed in 65 patients at the University of Michigan Medical Center. Postoperative
      thin-cut computed tomographic scans were obtained in 52 of these patients who
      were available to enroll in the study. An impartial neuroradiologist evaluated
      224 screws by use of a standardized grading scheme. All levels of the thoracic
      spine were included in the study. RESULTS: Chart review revealed no incidence of
      neurological, cardiovascular, or pulmonary injury. Of the 224 screws reviewed,
      there were 19 cortical violations (8.5%). Eleven (4.9%) were Grade II (< or =2
      mm), and eight (3.6%) were Grade III (>2 mm) violations. Only five screws (2.2%),
      however, were thought to exhibit unintentional, structurally significant
      violations. Statistical analysis revealed a significantly higher rate of cortical
      perforation in the midthoracic spine (T4-T8, 16.7%; T1-T4, 8.8%; and T9-T12,
      5.6%). CONCLUSION: The low rate of cortical perforations (8.5%) and structurally
      significant violations (2.2%) in this retrospective series compares favorably
      with previously published results that used anatomic landmarks and intraoperative
      fluoroscopy. This study provides further evidence that stereotactic placement of
      pedicle screws can be performed safely and effectively at all levels of the
      thoracic spine.

PMID- 11322438
TI  - Surgical management of middle cerebral artery aneurysms.

PMID- 11322439
TI  - Serial intraoperative magnetic resonance imaging of brain shift.
AB  - OBJECTIVE: A major shortcoming of image-guided navigational systems is the use of
      preoperatively acquired image data, which does not account for intraoperative
      changes in brain morphology. The occurrence of these surgically induced
      volumetric deformations ("brain shift") has been well established. Maximal
      measurements for surface and midline shifts have been reported. There has been no
      detailed analysis, however, of the changes that occur during surgery. The use of
      intraoperative magnetic resonance imaging provides a unique opportunity to obtain
      serial image data and characterize the time course of brain deformations during
      surgery. METHODS: The vertically open intraoperative magnetic resonance imaging
      system (SignaSP, 0.5 T; GE Medical Systems, Milwaukee, WI) permits access to the
      surgical field and allows multiple intraoperative image updates without the need
      to move the patient. We developed volumetric display software (the 3D Slicer)
      that allows quantitative analysis of the degree and direction of brain shift. For
      25 patients, four or more intraoperative volumetric image acquisitions were
      extensively evaluated. RESULTS: Serial acquisitions allow comprehensive
      sequential descriptions of the direction and magnitude of intraoperative
      deformations. Brain shift occurs at various surgical stages and in different
      regions. Surface shift occurs throughout surgery and is mainly attributable to
      gravity. Subsurface shift occurs during resection and involves collapse of the
      resection cavity and intraparenchymal changes that are difficult to model.
      CONCLUSION: Brain shift is a continuous dynamic process that evolves differently
      in distinct brain regions. Therefore, only serial imaging or continuous data
      acquisition can provide consistently accurate image guidance. Furthermore, only
      serial intraoperative magnetic resonance imaging provides an accurate basis for
      the computational analysis of brain deformations, which might lead to an
      understanding and eventual simulation of brain shift for intraoperative guidance.

PMID- 11322440
TI  - Novel, compact, intraoperative magnetic resonance imaging-guided system for
      conventional neurosurgical operating rooms.
AB  - OBJECTIVE: Preliminary clinical experience with a novel, compact, intraoperative
      magnetic resonance imaging (MRI)-guided system that can be used in an ordinary
      operating room is presented. DESCRIPTION OF INSTRUMENTATION: The system features
      an MRI scanner integrated with an optical and MRI tracking system. Scanning and
      navigation, which are operated by the surgeon, are controlled by an in-room
      computer workstation with a liquid crystal display screen. The scanner includes a
      0.12-T permanent magnet with a 25-cm vertical gap, accommodating the patient's
      head. The field of view is 11 x 16 cm, encompassing the surgical area of
      interest. The magnet is mounted on a transportable gantry that can be positioned
      under the surgical table when not in use for scanning, thus rendering the
      surgical environment unmodified and allowing the use of standard instruments. The
      features of the integrated navigation system allow flap planning and
      intraoperative tracking based on updated images acquired during surgery.
      OPERATIVE TECHNIQUE: Twenty patients with brain tumors were surgically treated
      using craniotomy or trans-sphenoidal approaches. One patient underwent conscious
      craniotomy with cortical mapping, and two underwent electrocorticography.
      EXPERIENCE AND RESULTS: Planning was accurate. Resection control images were
      obtained for all patients during surgery, with precise localization of residual
      tumor tissue. There were no surgical complications related to the use of the
      system. CONCLUSION: This intraoperative MRI system can function in a normal
      operating room modified only to eliminate radiofrequency interference. The
      operative environment is normal, and standard instruments can be used. The
      scanning and navigation capabilities of the system eliminate the inaccuracies
      that may result from brain shift. This novel type of intraoperative MRI system
      represents another step toward the introduction of the modality as a standard
      method in neurosurgery.

PMID- 11322441
TI  - Fiducial point placement and the accuracy of point-based, rigid body
      registration.
AB  - OBJECTIVE: To demonstrate that the shape of the configuration of fiducial points
      is an important factor governing target registration error (TRE) in point-based,
      rigid registration. METHODS: We consider two clinical situations: cranial
      neurosurgery and pedicle screw placement. For cranial neurosurgery, we apply
      theoretical results concerning TRE prediction, which we have previously derived
      and validated, to three hypothetical fiducial marker configurations. We
      illustrate the profile of expected TRE for each configuration. For pedicle screw
      placement, we apply the same theory to a common anatomic landmark configuration
      (tips of spinous and transverse processes) used for pedicle screw placement, and
      we estimate the error rate expected in placement of the screw. RESULTS: In the
      cranial neurosurgery example, we demonstrate that relatively small values of TRE
      may be achieved by using widely spread fiducial markers and/or placing the
      centroid of the markers near the target. We also demonstrate that near-collinear
      marker configurations far from the target may result in large TRE values. In the
      pedicle screw placement example, we demonstrate that the screw must be
      approximately 4 mm narrower than the pedicle in which it is implanted to minimize
      the chance of pedicle violation during placement. CONCLUSION: The placement of
      fiducial points is an important factor in minimizing the error rate for point
      based, rigid registration. By using as many points as possible, avoiding near
      collinear configurations, and ensuring that the centroid of the fiducial points
      is as near as possible to the target, TREs can be minimized.

PMID- 11322442
TI  - Comparison of thalamotomy and pallidotomy for the treatment of dystonia.
AB  - OBJECTIVE: Thalamotomy and, more recently, pallidotomy have been used to treat
      selected patients with intractable dystonia, although few studies have compared
      the effectiveness of these two surgical procedures. In this study, we compare our
      results using thalamotomy and pallidotomy to treat patients with different forms
      of dystonia, and we discuss our results in the context of other published series.
      METHODS: Thirty-two patients with intractable dystonia underwent thalamotomy (n =
      18) or pallidotomy (n = 14). Dystonia was classified according to cause and
      distribution, and each patient was evaluated postoperatively at two or more time
      points, using a global outcome scale. RESULTS: Although comparisons are limited
      by differences between the two surgical groups, including longer follow-up
      periods for the thalamotomy group, differences in symptom distribution, and more
      bilateral procedures for the pallidotomy group, patients with primary dystonia
      who underwent pallidotomies demonstrated significantly better long-term outcomes
      than did patients who underwent thalamotomies (P = 0.0467). Patients with
      secondary dystonia experienced more modest improvements after either procedure,
      with little or no difference in outcomes between the two procedures. CONCLUSION:
      For patients with primary dystonia, pallidotomy seems to result in better
      outcomes than does thalamotomy.

PMID- 11322443
TI  - Endoscopic endonasal cavernous sinus surgery: an anatomic study.
AB  - OBJECTIVE: The endoscopic surgical anatomy of the cavernous sinus was studied to
      establish an anatomic basis for endoscopic endonasal cavernous sinus surgery.
      METHODS: Five adult cadaveric heads were studied with 0-, 30-, and 70-degree 4-mm
      rod-lens endoscopes. The posterior wall of the sphenoidal sinus was approached
      via a paraseptal, middle turbinectomy, or middle meatal approach. RESULTS: The
      posterior bony wall of the sphenoidal sinus is subdivided into five vertical
      compartments: midline, bilateral paramedian, and bilateral lateral. The midline
      vertical compartment consists of the planum sphenoidale, tuberculum sellae,
      sella, and clival indentation. The paramedian vertical compartment is composed of
      the medial third of the optic canal and the carotid artery protuberance. The
      lateral vertical compartment contains four bony protuberances (optic, cavernous
      sinus apex, maxillary, and mandibular) and three depressions (carotico-optic,
      ophthalmomaxillary [V1-V2], and maxillomandibular [V2-V3]). The three depressions
      form anatomic triangles at the lateral vertical compartment: the optic strut
      triangle, which is bordered by the optic nerve, carotid artery, and oculomotor
      nerve (IIIrd cranial nerve); the V1-V2 triangle; and the V2-V3 triangle. The
      internal carotid artery at the posterior wall of the sphenoidal sinus can be
      subdivided into two main segments: the parasellar and the paraclival. The vidian
      canal is a landmark that leads to the foramen lacerum, the mandibular nerve, and
      the pterygopalatine fossa. CONCLUSION: Endoscopic anatomy of the cavernous sinus
      has been studied via an endonasal route in cadaveric specimens to provide an
      anatomic basis for endoscopic endonasal cavernous sinus surgery.

PMID- 11322444
TI  - Jugular foramen: microscopic anatomic features and implications for neural
      preservation with reference to glomus tumors involving the temporal bone.
AB  - OBJECTIVE: Our goals were to study the normal histological features of the
      jugular foramen, compare them with the histopathological features of glomus
      tumors involving the temporal bone, and thus provide insight into the surgical
      management of these tumors with respect to cranial nerve function. METHODS: Ten
      jugular foramen blocks were obtained from five human cadavers after removal of
      the brain. Microscopic studies of these blocks were performed, with particular
      attention to fibrous or bony compartmentalization of the jugular foramen, the
      relationships of the caudal cranial nerves to the jugular bulb/jugular vein and
      internal carotid artery, and the fascicular structures of the nerves. In
      addition, we studied the histopathological features of 11 glomus tumors involving
      the temporal bone (10 patients), with respect to nerve invasion, associated
      fibrosis, and carotid artery adventitial invasion. RESULTS: A dural septum
      separating the IXth cranial nerve from the fascicles of Cranial Nerves X and XI,
      at the intracranial opening, was noted. Only two specimens, however, had a septum
      (one bony and one fibrous) producing internal compartmentalization of the jugular
      foramen. The cranial nerves remained fasciculated within the foramen, with the
      vagus nerve containing multiple fascicles and the glossopharyngeal and accessory
      nerves containing one and two fascicles, respectively. All of these nerve
      fascicles lay medial to the superior jugular bulb, with the IXth cranial nerve
      located anteriorly and the XIth cranial nerve posteriorly. All nerve fascicles
      had separate connective tissue sheaths. A dense connective tissue sheath was
      always present between the IXth cranial nerve and the internal carotid artery, at
      the level of the carotid canal. The inferior petrosal sinus was present between
      the IXth and Xth cranial nerves, as single or multiple venous channels. The
      glomus tumors infiltrated between the cranial nerve fascicles and inside the
      perineurium. They also produced reactive fibrosis. In one patient, in whom the
      internal carotid artery was also excised, the tumor invaded the adventitia.
      CONCLUSION: Within the jugular foramen, the cranial nerves lie anteromedial to
      the jugular bulb and maintain a multifascicular histoarchitecture (particularly
      the Xth cranial nerve). Glomus tumors of the temporal bone can invade the cranial
      nerve fascicles, and infiltration of these nerves can occur despite normal
      function. In these situations, total resection may not be possible without
      sacrifice of these nerves.

PMID- 11322445
TI  - Craniovertebral abnormalities in Type VI mucopolysaccharidosis (Maroteaux-Lamy
      syndrome).
AB  - INTRODUCTION: The craniovertebral abnormalities found in patients with Type VI
      mucopolysaccharidosis (Maroteaux-Lamy syndrome) are described, and the
      indications for and outcomes of surgery in this group are assessed. METHODS: The
      clinical histories and radiological findings in all patients with Type VI
      mucopolysaccharidosis treated at Royal Manchester Children's Hospital during the
      past 10 years were reviewed. RESULTS: The typical findings in patients with this
      disease are of canal stenosis at the level of the foramen magnum and upper
      cervical spine with or without cord compression. The stenosis is secondary to
      thickening of the posterior longitudinal ligament. Atlantoaxial instability is
      rare. Of nine patients under regular clinical review, four underwent
      decompressive surgery for cervical cord compression. Three of the four showed
      improvement in their neurological symptoms and signs postoperatively. Of the
      children reviewed, six had radiological evidence of cord compression, although
      only those with neurological signs or symptoms were treated surgically.
      DISCUSSION: Despite the often formidable anesthetic challenge, surgery is
      indicated in those patients who present with progressive neurological deficit due
      to cervical myelopathy. Surgery can be undertaken safely if the associated
      medical problems in these children are recognized and managed appropriately.

PMID- 11322446
TI  - Role of adenosine 5'-triphosphate in vasospasm after subarachnoid hemorrhage:
      human investigations.
AB  - OBJECTIVE: Adenosine 5'-triphosphate (ATP) is a vasoactive compound found in high
      concentrations inside erythrocytes. This compound may contribute to vasospasm
      after subarachnoid hemorrhage (SAH). We assessed the hypothesis that ATP
      contributes to vasospasm in humans. METHODS: ATP and hemoglobin concentrations
      were measured in cerebrospinal fluid (CSF) from humans with SAH and in blood
      incubated in vitro. The vasoactivity of the human CSF samples and of fractionated
      (fractions with molecular weight greater than or less than 10 kDa) and
      unfractionated blood incubated in vitro was assessed by application of samples to
      canine basilar artery segments under isometric tension. RESULTS: ATP in human CSF
      declined within 72 hours of SAH to concentrations too low to contract cerebral
      arteries. Vasoactivity of human CSF correlated with the concentration of
      hemoglobin. The vasoactivity of incubated erythrocyte hemolysates remained high
      despite a decline in ATP concentrations. Fractionation of incubated erythrocyte
      hemolysates showed that for incubation periods up to 7 days, all vasoactivity was
      in a fraction of molecular weight greater than 10 kDa. CONCLUSION: ATP is
      unlikely to contribute to vasospasm because the concentrations in CSF after SAH
      in humans are not high enough to cause vasospasm after 72 hours. The vasoactivity
      of erythrocyte hemolysate is not related to the ATP or ferrous hemoglobin content
      but may be related to the total hemoglobin content. Therefore, ATP is unlikely to
      be a major cause of clinically significant delayed vasospasm.

PMID- 11322447
TI  - Constitutive expression of growth-related oncogene and its receptor in
      oligodendrogliomas.
AB  - OBJECTIVE: Gliomas may result from transformation of glial precursor cells. In
      the developing rat central nervous system (CNS), a paracrine pathway involving
      the cytokines growth-related oncogene (GRO1) and platelet-derived growth factor
      (PDGF) A chain closely regulates oligodendrocyte precursor cell number. The
      purpose of the present study was to analyze whether abnormal expression and
      activity of the GRO1-PDGF pathway is present in human gliomas. METHODS: Tumor
      specimens were studied to compare the messenger ribonucleic acid with the protein
      expression of components of the GRO1-PDGF pathway. Neutralizing antibodies were
      used in vitro to analyze whether the pathway contributed to tumor cell
      proliferation. RESULTS: Immunohistochemistry demonstrated that all components of
      the GRO1-PDGF pathway (GRO1 protein, its receptor CXCR2, PDGF A chain, and its
      receptor PDGFalphaR) were expressed by tumor cells in 6 (86%) of 7 of
      oligodendrogliomas as well as by 0 of 4 diffuse astrocytomas (World Health
      Organization Grades II and III) and 2 (18%) of 11 glioblastomas. Analysis by
      reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent
      assay showed CXCR2 messenger ribonucleic acid and GRO1 protein expression were
      present in oligodendrogliomas. Functional analyses with neutralizing antibodies
      limited bromodeoxyuridine incorporation in vitro by oligodendroglioma tumor
      cells, demonstrating a requirement for the GRO1-PDGF pathway in the proliferation
      of these cells. CONCLUSION: The GRO1-PDGF pathway was primarily expressed and
      functional in oligodendrogliomas. The tightly controlled paracrine pathway that
      regulates oligodendrocyte precursor proliferation in the developing rodent CNS
      was constitutively active in most oligodendrogliomas in the present study. The
      presence of this aberrantly functioning oncogenic pathway in a subset of primary
      CNS tumors opens new avenues to glioma treatment that are based directly on the
      biology of the proliferative glial cell type, a novel strategy for primary CNS
      tumor therapy.

PMID- 11322448
TI  - Intracerebral hemorrhage-induced neuronal death.
AB  - OBJECTIVE: The mechanisms underlying neural injury in intracerebral hemorrhage
      (ICH) remain uncertain. The present two-part study investigated cell death in the
      region of ICH and its association with caspase-3 activation. METHODS: ICH was
      produced in adult rats by injection of 100 microl of autologous blood or saline
      into the right basal ganglia. The animals' brains were removed at 6 hours or at
      1, 3, 7, or 14 days after hemorrhage. Terminal deoxynucleotidyl transferase
      mediated deoxyuridine triphosphate-biotin in situ nick end-labeling (TUNEL) was
      used to detect deoxyribonucleic acid (DNA) fragmentation. TUNEL-positive cells
      were quantified. Caspase-3 activation was measured by Western blotting and
      immunohistochemistry. Double labeling was used to compare TUNEL with caspase-3
      distribution and to identify the cell types affected. TUNEL-positive cells were
      also quantified at 6 hours, 1 day, and 3 days after injection of 5 U of thrombin
      into the right basal ganglion. RESULTS: At 6 hours, TUNEL-positive cells appeared
      in the ICH model (but not in the saline control brains) and were present for more
      than 2 weeks after ICH, peaking at 3 days. Western blot analysis revealed that
      the increase in immunoreactivity for the activated caspase-3 precedes that of DNA
      fragmentation, peaking at 1 day after ICH and declining thereafter.
      Immunohistochemistry analysis showed nucleus translocation of caspase-3 after
      ICH. Double-labeling studies demonstrated that both neurons and astrocytes
      surrounding the clot were TUNEL-positive. In addition, TUNEL and caspase-3 were
      colocalized in the same cells. Intracerebral thrombin injection elicited DNA
      fragmentation similar to that observed after the injection of blood. CONCLUSION:
      Double-strand breaks in genomic DNA and induction of caspase-3 were demonstrated
      adjacent to parenchymal hematoma in the animals' brains. These results provide
      evidence that cell loss after ICH is associated with activation of caspase-3.

PMID- 11322449
TI  - Effects of nitric oxide on reactive oxygen species production and infarction size
      after brain reperfusion injury.
AB  - OBJECTIVE: Deleterious effects of strokes may be ameliorated when thrombolysis
      (i.e., with recombinant tissue plasminogen activator) restores circulation.
      However, reperfusion injury, mediated by oxygen free radicals (reactive oxygen
      species [ROS]), may limit the benefits of recombinant tissue plasminogen
      activator treatment. We hypothesized that, during reperfusion, exogenous nitric
      oxide (NO) would reduce stroke size by quenching ROS. METHODS: To investigate
      this hypothesis, we used two in vivo ischemia-reperfusion models, i.e.,
      autologous cerebral embolism in rabbits and filament middle cerebral artery
      occlusion in rats. Using these models, we measured ROS levels (rabbit model) and
      stroke volumes (rat model) in response to transient ischemia, with and without
      intracarotid administration of ultrafast NO donor proline NO (proliNO). RESULTS:
      In the rabbit cerebral embolism model, intracarotid administration of proliNO
      (10(-6) mol/L) (n = 6) during reperfusion decreased free radical levels from 538
      +/- 86 nmol/L in the vehicle-treated group (n = 7) to 186 +/- 31 nmol/L (2,3'
      dihydroxybenzoic acid; P < 0.001) and from 521 +/- 86 nmol/L (n = 7) to 201 +/-
      39 nmol/L (2,5'-dihydroxybenzoic acid; P < 0.002). In the rat middle cerebral
      artery occlusion model, intracarotid administration of proliNO (10(-5) mol/L) (n
      = 10) during reperfusion reduced the brain infarction volume from 256 +/- 48 mm3
      in the vehicle-treated group (n = 8) to 187 +/- 41 mm3 (P < 0.005). In both
      experimental groups, intracarotid infusion of proliNO did not affect regional
      cerebral blood flow, mean arterial blood pressure, or brain and body
      temperatures. CONCLUSION: The beneficial effects of early restoration of cerebral
      circulation after cerebral ischemia were enhanced by intracarotid infusion of
      proliNO, most likely because of ROS scavenging by NO. These findings suggest the
      possibility of preventive treatment of reperfusion injury using NO donors.

PMID- 11322450
TI  - Efficacy of intrathecal liposomal fasudil for experimental cerebral vasospasm
      after subarachnoid hemorrhage.
AB  - OBJECTIVE: To investigate the safety and efficacy of liposomal fasudil in a
      sustained-release form for the prevention of cerebral vasospasm after
      subarachnoid hemorrhage (SAH). METHODS: Eighteen rats were divided into three
      groups, each of which received 2.5 mg/kg of liposomal fasudil, 5 mg/kg of
      liposomal fasudil, or drug-free liposomes after SAH. Next, experimental SAH was
      induced in 15 dogs by injection of autologous arterial blood into the cisterna
      magna twice after baseline vertebral angiography. In six dogs, 0.94 mg/kg of
      liposomal fasudil was injected into the cisterna magna (treatment group). In four
      dogs, drug-free liposomes were similarly injected (placebo group), and the
      remaining five dogs were not treated with liposomal injection after SAH (control
      group). Angiography was repeated on Day 7, and cerebrospinal fluid was collected
      before the dogs were killed. RESULTS: A high dose of liposomal fasudil caused no
      significant changes in mean arterial blood pressure and did not induce seizures
      during the observation period. Gross and microscopic examination of the brains
      revealed no abnormalities, but severe vasospasm was noted in the rat basilar
      artery, mainly in the group treated with drug-free liposomes. Likewise, in the
      canine placebo and control groups, significant vasospasm occurred in the basilar
      artery on Day 7. In the treatment group, vasospasm in the basilar artery was
      significantly ameliorated (P < 0.01). In vivo, 90% of fasudil was released from
      liposomes in the cerebrospinal fluid. CONCLUSION: A single injection of
      intrathecal liposomal fasudil is safe and effective for the prevention of
      vasospasm in experimental SAH.

PMID- 11322451
TI  - Inhibition of endothelin-converting enzyme activity in the rabbit basilar artery.
AB  - OBJECTIVE: Endothelin (ET)-1 may be involved in the regulation of cerebrovascular
      resistance under pathological conditions, most notably during the development of
      vasospasm after subarachnoid hemorrhage. Blocking ET-converting enzyme activity
      may be a promising approach to the prevention of cerebral vasospasm after
      subarachnoid hemorrhage. METHODS: In this study, the effects of several putative
      ET-converting enzyme inhibitors were investigated after intracisternal
      application in rabbits, to inhibit basilar artery contractions induced by big ET
      1 (2 x 10(-6) mol/L). RESULTS: In the group pretreated with [D-Val22]big ET-1[16
      38] (2 x 10(-5) mol/L) (n = 8), the angiographically measured diameter of the
      basilar artery changed from 0.63 +/- 0.12 mm to 0.66 +/- 0.12 mm. In the control
      group (n = 8), the diameter of the basilar artery decreased from 0.71 +/- 0.13 mm
      to 0.57 +/- 0.15 mm. These results corresponded to an increase in vessel diameter
      of 5 +/- 10% in the treatment group and a decrease in vessel diameter of 20 +/-
      16% in the control group (P = 0.014). In the group pretreated with captopril (2 x
      10(-4) mol/L) (n = 8), the angiographically measured diameter of the basilar
      artery changed from 0.64 +/- 0.11 mm to 0.71 +/- 0.10 mm. These results
      corresponded to an increase in vessel diameter of 14 +/- 19% in the treatment
      group, compared with a decrease in vessel diameter of 20 +/- 16% in the control
      group (P = 0.014). CONCLUSION: These results demonstrate that [D-Val22]big ET
      1[16-38] and captopril act as highly potent ET-converting enzyme inhibitors,
      affecting big ET-1-induced contraction of the rabbit basilar artery.

PMID- 11322452
TI  - Victor Horsley on "trephining in pre-historic times".
AB  - Victor Horsley was intrigued by newly discovered, ancient trepanned skulls,
      especially those that revealed that the operation was performed on living
      patients. He examined the man-made openings as an expert on the locus of the
      primate motor cortex and as a surgeon who had successfully removed parts of the
      motor cortex to treat Jacksonian epilepsy. He postulated that trepanation
      originated as a way to treat pain and epilepsy caused by depressed cranial
      fractures over the motor cortex. Like Broca before him, Horsley helped create the
      exciting Zeitgeist that led others in the late-1 800s to explore, ponder, and
      write about ancient trepanned skulls.

PMID- 11322453
TI  - The Department of Neurosurgery at Seoul National University: past, present, and
      future.
AB  - The Department of Neurosurgery at Seoul National University College of Medicine
      is one of the oldest neurosurgical departments in Korea, and it is a center of
      academic leadership in neurosurgery. In September 1957, the department was
      established by Bo Sung Sim, and it has produced many leaders of neurosurgery in
      Korea. Chairmen Bo Sung Sim, Kil Soo Choi, Dae Hee Han, and Byung-Kyu Cho each
      brought special skills and talents to the development of the department. The
      current and fifth chair, Hyun Jib Kim, assumed the chairmanship in July 2000. The
      department comprises 11 full-time faculty members, 5 fellows, and 14 residents.
      More than 1,700 neurosurgical procedures are performed annually in four operating
      theaters. A gamma knife was installed in 1997, and approximately 200 gamma knife
      procedures are performed each year. In addition to clinical activities, research
      and education for graduate and postgraduate students are also particular
      strengths of the department. This article traces the clinical, academic, and
      scientific development of the department, its present activities, and its future
      direction.

PMID- 11322454
TI  - Reversal of increased intracranial pressure with removal of a torcular
      epidermoid: case report.
AB  - OBJECTIVE AND IMPORTANCE: Venous obstruction has been postulated as a cause of
      increased intracranial pressure, but it has been documented rarely. We present a
      case of obstruction of the torcula by a slow-growing epidermoid. The tumor caused
      increased intracranial pressure, which was relieved when it was excised. In
      addition, the torcular epidermoid is associated with a bifid straight sinus.
      CLINICAL PRESENTATION: A 35-year-old man presented with a headache and a lump on
      the back of the head. Physical examination revealed a firm, bony lesion
      approximately 4 x 4 cm in size. Lumbar puncture demonstrated an intraspinal
      pressure of 39 cm H2O. Neuroradiological studies revealed an epidermoid that
      compressed and almost completely occluded the torcula. INTERVENTION: After the
      tumor was resected, the intraspinal pressure decreased to 19 cm H2O and remained
      stable 6 months later. CONCLUSION: Pure venous obstruction causes increased
      intracranial pressure. Removal of the obstruction relieves the intracranial
      hypertension. In addition, computed tomographic venography is a safe and easy
      method of documenting torcular anatomy, and it was useful in the follow-up of
      this patient. Computed tomographic venography can demonstrate a double straight
      sinus, which is a congenital variant that may be associated with the epidermoid.

PMID- 11322455
TI  - Does craniopharyngioma metastasize? Case report and review of the literature.
AB  - OBJECTIVE AND IMPORTANCE: A rare case of recurrent craniopharyngioma at an
      ectopic location is described. This recurrence suggested cerebrospinal fluid
      seeding. CLINICAL PRESENTATION: A 65-year-old man presented for follow-up of
      persisting visual field defect. He had undergone total resection of a suprasellar
      craniopharyngioma via a subfrontal approach 3 years before presentation. Recent
      magnetic resonance imaging scans revealed a contrast-enhancing tumor with cystic
      and solid components at the right temporal lobe. The primary tumor bed was
      intact. INTERVENTION: A temporal craniotomy was performed for total resection of
      the tumor. Intraoperative findings revealed that the recurrent tumor was
      anatomically unrelated to the previous surgical track. Histological studies of
      the tumor specimen demonstrated a benign craniopharyngioma. Cerebrospinal fluid
      spreading was suspected to be the sole route for the recurrence. CONCLUSION: The
      case presented here and a review of reports on remote recurrence of
      craniopharyngioma suggest that care is required during intraoperative handling of
      the tumor and that long-term follow-up should be performed even in patients whose
      primary tumor was resected completely.

PMID- 11322456
TI  - Intracranial metastatic parathyroid carcinoma: case report.
AB  - OBJECTIVE AND IMPORTANCE: Parathyroid carcinoma is a rare entity, and fewer than
      200 cases have been described. It is a slowly progressive disease characterized
      by frequent recurrences and local metastases. Most patients with parathyroid
      carcinoma die from metabolic complications of hyperparathyroidism. Five-year
      survival rates range from 25 to 50%. Functional parathyroid carcinoma is a rare
      cause of hyperparathyroidism that affects only 0.32 to 5% of all patients who
      undergo surgery for hypercalcemia. A review of the literature revealed only one
      other reported case of metastatic intracranial parathyroid carcinoma, in a
      patient who experienced local recurrence and metastatic disease when she was
      diagnosed with an intracranial lesion. CLINICAL PRESENTATION: We report the case
      of a 44-year-old African-American man with recent-onset, right lower-extremity
      weakness and hypercalcemia 4 years after he underwent a parathyroidectomy for
      parathyroid carcinoma. At presentation, his parathyroid level was 467 pg/ml, and
      his serum calcium level was 15.2 mg/dl. Imaging studies revealed an isolated
      enhancing left mesial frontoparietal mass. A systemic Cardiolite study
      demonstrated a single focus of radiotracer uptake in this region. No abnormal
      uptake was demonstrated in the neck or elsewhere. INTERVENTION: The patient
      underwent a frameless stereotactic interventional magnetic resonance imaging
      guided resection via a parasagittal interhemispheric approach. Pathological
      findings were consistent with parathyroid carcinoma. After resection, his right
      lower-extremity weakness and secondary hyperparathyroidism resolved. CONCLUSION:
      The typical natural history of parathyroid carcinoma concludes with death from
      complications of hyperparathyroidism. This case report supports aggressive
      surgical management to eliminate all parathyroid hormone-secreting malignant
      tissue and prevent metabolic complications. In this patient, intraoperative
      magnetic resonance imaging was helpful to ensure complete resection.

PMID- 11322457
TI  - Distant wounded glioma syndrome: report of two cases.
AB  - OBJECTIVE AND IMPORTANCE: We describe two cases of distant wounded glioma
      syndrome complicating surgical resection of multifocal glioblastoma multiforme.
      This clinical entity was previously described as a local phenomenon resulting in
      postoperative hemorrhaging within the cavity of partially resected tumors. These
      cases are unique, in that the postoperative hemorrhaging occurred within distant
      tumor nodules after gross total resection of the primary lesion. CLINICAL
      PRESENTATION AND INTERVENTION: Two middle-aged men without known risk factors for
      postoperative hemorrhaging presented with multifocal glioblastoma multiforme.
      Each underwent surgical resection of the deficit-producing lesion and developed
      hemorrhage at distant tumor sites that were not directly manipulated during the
      surgical procedures. The distant hemorrhage caused new neurological deficits,
      with severe morbidity. CONCLUSION: We postulate that distant wounded glioma
      syndrome is a distinct clinical entity that causes remote postoperative
      hemorrhaging and that tumor-induced coagulopathy triggered by surgery seems to
      create a hypocoagulable state that is most concentrated within brain tissue.
      Because of their rich vascularity, these distant tumor nodules are more
      susceptible to hemorrhage, resulting from coagulation changes after tumor
      resection, than are other sites. They also exhibit increased blood flow after
      resection of a large mass, because of autoregulatory dysfunction induced by
      peritumoral edema, increasing the likelihood of hemorrhage at these sites.

PMID- 11322458
TI  - Primary myxoma of the temporal bone in a 17-year-old boy: case report.
AB  - OBJECTIVE AND IMPORTANCE: Only two cases of primary intracranial myxomas have
      been described previously in the literature: one patient had a primary
      intracranial myxoma in the pituitary fossa, and the other patient's myxoma was
      located in the posterior fossa. CLINICAL PRESENTATION: A rare case of primary
      myxoma of the temporal bone in a 17-year-old boy is described. The patient
      presented with a history of progressive left-sided hearing loss and increasing
      headaches of a few months' duration. INTERVENTION: An initial draining procedure
      in the left ear revealed extant mucous material, and further investigation showed
      a large calcified lesion involving the petrous and temporal bones and filling the
      middle fossa. At surgery, a large mucoid-appearing tumor was removed. The tumor
      pathology revealed a primary myxoma with bone and meningeal involvement. No
      clinical or histopathological evidence that it was a metastatic lesion was found.
      CONCLUSION: The features of myxomas on computed tomographic and magnetic
      resonance imaging, the histopathology, and surgical considerations are discussed.

PMID- 11322459
TI  - Aneurysms of the lateral spinal artery: report of two cases.
AB  - OBJECTIVE AND IMPORTANCE: The goal of this report was to describe aneurysms
      arising from the lateral spinal artery. The locations of aneurysms contributing
      to subarachnoid hemorrhage (SAH) have been well characterized and are primarily
      in the circle of Willis or at the bifurcation points of the internal carotid
      artery or the vertebrobasilar system. Although the spinal arteries are also in
      direct communication with the subarachnoid space, aneurysms of these arteries
      that lead to SAH are rare. To date, only aneurysms of the anterior and posterior
      spinal arteries have been described. In this communication, we report two
      patients with aneurysms of the lateral spinal artery who presented with SAH.
      CLINICAL PRESENTATION: Review of our neurointerventional database from 1997 to
      the present revealed two patients with lateral spinal artery aneurysms. The
      medical records, as well as the operative and radiological findings, were
      reviewed for both patients. In both cases, the lateral spinal arteries were
      involved as collateral pathways for occlusive vertebral lesions, suggesting
      hemodynamic stress as a cause. INTERVENTION: Endovascular treatment was attempted
      in both cases and was successful in one; open surgery, with aneurysm resection,
      was performed in the other case. We review the vascular anatomic features of the
      spinal cord as they relate to the lateral spinal artery, as well as treatment
      options for lateral spinal artery aneurysms. CONCLUSION: Lateral spinal artery
      aneurysms are a rare cause of SAH. Both endovascular and surgical treatment
      options are available.

PMID- 11322460
TI  - Contralateral pterional approach to a giant internal carotid-ophthalmic artery
      aneruysm: technical case report.
AB  - OBJECTIVE AND IMPORTANCE: The contralateral approach to internal carotid
      ophthalmic artery aneurysms has been used in selected cases but has rarely been
      described for a giant internal carotid artery aneurysm. We report a case of giant
      aneurysm that was successfully clipped via the contralateral pterional approach.
      CLINICAL PRESENTATION: A 69-year-old woman was found to have two aneurysms: a
      small aneurysm at the left internal carotid-posterior communicating artery and a
      giant aneurysm at the right internal carotid-ophthalmic artery. INTERVENTION: A
      direct clipping operation was performed via the left pterional approach. After
      the small left internal carotid artery aneurysm was clipped, the contralateral
      giant aneurysm was further exposed and successfully clipped by use of the same
      approach via the prechiasmatic space. CONCLUSION: The contralateral pterional
      approach can be applied even for a giant aneurysm of the carotid-ophthalmic
      artery aneurysm when the neck of the aneurysm is small and when there is a space
      between the anterior wall of the aneurysm and the tuberculum sellae. Furthermore,
      such a giant aneurysm can be clipped more easily and safely via the contralateral
      approach without compromising visual functions. To our knowledge, this is the
      first reported case of a giant internal carotid-ophthalmic artery aneurysm
      approached contralaterally. The feasibility of this approach can be assessed
      preoperatively by three-dimensional computed tomographic angiography as well as
      by conventional cerebral angiography.

PMID- 11322461
TI  - Significance of non-level walking on transtibial prosthesis fitting with
      particular reference to the effects of anterior-posterior alignment.
AB  - Despite the fact that non-level walking is known to be important for prosthesis
      fitting, its clinical significance has not been investigated. In this study, the
      acceptable prosthesis alignment ranges of six subjects with transtibial
      amputation on level and non-level walking were determined and compared. With the
      aid of a recently developed alignment jig, prosthesis fitting was performed for
      each subject with varied anterior-posterior (AP) alignments. Conventional
      assessments and the subjects' comment were used to determine whether the
      alignment was acceptable or not. The results showed that the acceptable alignment
      range for non-level walking consistently fell within and was significantly
      smaller than that for level walking with p<0.05. It was evident that non-level
      walking is important for better approximation of optimum alignment and should be
      included in routine prosthesis fitting.

PMID- 11322462
TI  - Meeting the intent of ADA in sidewalk cross-slope design.
AB  - Recent work has indicated that prior research is insufficient to support the ADA
      Accessibility Guidelines' (ADAAG) 2% maximum cross-slope requirement for
      sidewalks. In addition, the present ADAAG are inflexible in that they do not
      consider deviations from this maximum for short sections of sidewalk, such as at
      driveway crossings, which can be of significant concern for state and local
      departments of transportation. Based upon these findings, a study was undertaken
      to evaluate the usable range of sidewalk cross-slopes by explicitly considering
      user perception and effort. Twenty subjects ranging widely in age and type of
      mobility aid participated in field surveys where they traversed different
      sidewalk sections varying in cross-slope, primary grade, length, width, and other
      characteristics. This paper illustrates the use of weighted-least-squares and
      ordered-probit regression models for analysis of disabled-user response to
      sidewalk characteristics. The results of these models permit estimation of
      maximum sidewalk cross-slope consistent with the intent and spirit of ADA. These
      are estimated to be 4%--where feasible-and 10%--where unfavorable construction
      conditions exist. Such results should prove useful for consideration of the final
      requirements of ADA on this topic. However, larger sample sizes and a stronger
      recognition of the population of interest are necessary before definitive,
      legislated maxima can be ascertained.

PMID- 11322463
TI  - Noise reduction in hearing aids: a review.
AB  - Background noise is particularly damaging to speech intelligibility for people
      with hearing loss. The problem of reducing noise in hearing aids is one of great
      importance--and great difficulty. The problem has been addressed in many
      different ways over the years. The techniques used range from relatively simple
      forms of filtering to advanced signal processing methods. This paper provides a
      brief overview, in nontechnical language, of the issues involved and the various
      approaches to solving the problem.

PMID- 11322464
TI  - SLO radiant power and brightness.
AB  - Available output in the Scanning Laser Ophthalmoscope (SLO) may be expressed as
      radiant power at the beam pivot (SLO exit pupil), in units of microwatts
      (microW). This power corresponds to dimensions of brightness (like luminance and
      retinal illuminance) and to a range of related measures (like cd/m2, lm/m2, and
      the troland value) in both free and Maxwellian views. We demonstrate that the
      conversion factor power/troland=1.26*10(-3) microW and 3.15*10(-4) microW for SLO
      nominal visual angles 40 degrees and 20 degrees, respectively. The factor permits
      measured SLO power to be expressed in units of brightness and (inversely)
      brightnesses of everyday objects to be expressed in units of SLO power. Examples
      of both conversions are given. Reference to the literature demonstrates the
      importance of expressing SLO power in brightness terms common to everyday
      activities and to visual function-testing instruments besides the SLO.

PMID- 11322465
TI  - SLO power calibration.
AB  - We present a method for calibrating the Scanning Laser Ophthalmoscope (SLO) that
      predicts radiant power at any of 256 grayscale values (gsv) and 12 polarized
      filter (polarizer) levels. Predicted power values, p(gsv), were determined by
      substitution into polynomials linearly transformed to old or new power at p(0)
      and p(255). This was compared with observed power values at 125 levels of
      attenuation/session. Prediction accuracy was the proportion of nonsignificant
      pairwise comparisons (t-test, p=0.0001). We found that power transformation
      between polarizers and within sessions has both linear and nonlinear
      characteristics. Within polarizer and between sessions, however, power
      transformation has linear characteristics. A 5th-degree polynomial was
      individually fit, at each polarizer, to session 1 power distributions of 9 gsv
      steps (0, 31, 63, 95, 127, 159, 191, 223, 255). When adjusted to p(255) and p(0)
      in new sessions, we obtained p(gsv) that predicted power at 25 gsv * 5 polarizers
      for 18 days with an accuracy of about 0.84. When only adjusted to p(255),
      predictive accuracy was 0.81.

PMID- 11322466
TI  - Testing the validity of erythema detection algorithms.
AB  - Dermatology has quantified skin color for monitoring progress of treatments. The
      most common and effective means of erythema detection is visual inspection of the
      skin. However, for people with darkly pigmented skin, erythema can be masked by
      melanin. Tissue Reflectance Spectroscopy (TRS) is a noninvasive method of
      quantifying skin color. Most commonly, TRS quantifies erythema caused by
      cosmetics, topical ointments, UV light, or other irritants. Recently, TRS has
      been used to characterize the presence of erythema due to reactive hyperemia or
      Stage I pressure ulcers. The objective of this study was to compare the
      reliability and validity of erythema detection algorithms by determining their
      sensitivity and specificity. Two algorithms, Diffey and Helen Hayes Hospital
      (HHH), had sensitivity exceeding 85% and specificity exceeding 75%, but most
      algorithms demonstrated adequate validity across all subjects. The validity of
      the HHH algorithm did not change with the skin pigmentation of the subject. The
      results of this comparison will be useful to researchers interested in using TRS
      to detect erythema in people with different skin pigment levels.

PMID- 11322467
TI  - Reduced push forces accompany device use during sliding transfers of seated
      subjects.
AB  - PURPOSE: Research verifying the ability of various devices to reduce the forces
      required for transfers is virtually nonexistent. Therefore, we compared the push
      forces required to move passive seated subjects across a horizontal surface when
      four different methods were employed. SUBJECTS: 10 men and 14 women (weight 49.1
      96.8 kg) served as subjects. METHODS AND MATERIALS: Passive subjects were moved
      horizontally across a treatment table that had a vinyl-covered foam mat on top.
      They sat either directly on the mat or on a vinyl sliding board (Ross Easy
      Glide), on a fabric tube (Ross Mini-Slide), or on a fabric tube on top of a
      sliding board on top of the mat. Subjects were pushed horizontally by each of the
      two authors via a hand-held dynamometer that was placed over their greater
      trochanter. ANALYSES: To examine interrater reliability of push forces,
      intraclass correlation coefficients (ICCs) were calculated for each transfer
      method using the two authors' measurements. Validity was confirmed using Pearson
      correlations to test the relationship between subjects' weights and the forces
      required to push them. A repeated measures analysis of variance (ANOVA) and pair
      wise post hoc tests were used to compare the forces associated with the four
      methods. RESULTS: The ICCs for push forces ranged from 0.77 to 0.91 depending on
      the transfer method. The push forces associated with the four transfer methods
      (no device=200.7+/-40.8 N, sliding board=120.5+/-27.7 N, fabric tube=105.8+/-26.1
      N, fabric tube and sliding board=84.2+/-13.4 N,) differed significantly (F=273.9,
      p<0.001). CONCLUSIONS: This study demonstrates that assistive devices can greatly
      reduce the forces required to move seated subjects horizontally. The sliding
      board and the fabric tube were most effective when used together. Such devices
      have the potential to make transfers easier for individuals performing seated
      transfers and to reduce the risk of injury among individuals assisting them.

PMID- 11322468
TI  - The design of a compliant composite crutch.
AB  - Ambulation by crutches takes up to twice the energy of normal gait and can lead
      to injuries of the hands and arms. The compliant composite forearm crutch
      described in this article seeks to address these problems. The new crutch is made
      of a single composite piece and has an S-curve in the main body to provide shock
      absorption and return of energy with the goal of reducing impact and repetitive
      injuries. It is lighter and, we expect, more durable than current crutches due to
      the lack of interfacing parts. The new forearm cuff design provides retention of
      the crutch on the arm without a pivot. The contoured forearm cuff with wrist
      supports and padding is intended to provide added comfort and support. These
      features are integrated into an aesthetic, high-tech-looking design in
      charcoal/black color. (See Figure 1) Initial testing with seven users yielded
      favorable response to function and appearance. Quantitative analysis has
      identified improvements needed for future iteration in design. These include 1)
      making the wrist supports more narrow and placed down one inch, 2) optimizing the
      stiffness of the top curve of the S-shape, and 3) testing the crutch for motion
      and energy requirements in use.

PMID- 11322469
TI  - Physical capacity and race performance of handcycle users.
AB  - The purpose of this study was to determine physical capacity, gross efficiency
      (GE), and physical strain (PS) of 16 male handcycle users during a 10K race, and
      to relate these to race performance. All subjects used a handcycle system
      attached to their own wheelchair and were classified into a group with (A1/A2;
      N=10) and without (A3; N=6) upper-limb impairments. The PS was defined as the
      mean heart rate during the race, expressed relative to the heart rate reserve
      (%HRR). Race performance was defined as the mean race velocity (Vrace). Maximal
      power output (POmax), VO2peak, and GE (at 28 W) were determined in a graded
      treadmill exercise test. POmax (55+/-25 versus 129+/-26 W), VO2peak (1.11+/-0.4
      versus 2.12+/-0.4 L x min(-1)) and Vrace (13.6+/-3 versus 19.9+/-3 km x hr(-1))
      were different between A1/A2 and A3 (p<0.001), whereas PS (80+/-9 versus 88+/-9
      %HRR; p=0.12) and GE (10.9+/-1.4 versus 9.7+/-0.9%; p=0.09) were not. POmax,
      VO2peak, and PS were associated (p<0.05) with Vrace (R=0.91, 0.90, and 0.66).
      Regression analysis showed that after VO2peak, GE added another 9 percent to the
      explanation of the variance of Vrace (R2=0.89). In conclusion, attainable
      handcycling POmax is markedly high and strongly related to race performance. The
      high PS during the race suggests that handcycling is well suited for aerobic
      training for most groups of wheelchair users.

PMID- 11322470
TI  - Dynamic calibration of a wheelchair dynamometer.
AB  - The inertia and resistance of a wheelchair dynamometer must be determined in
      order to compare the results of one study to another, independent of the type of
      device used. The purpose of this study was to describe and implement a dynamic
      calibration test for characterizing the electro-mechanical properties of a
      dynamometer. The inertia, the viscous friction, the kinetic friction, the motor
      back-electromotive force constant, and the motor constant were calculated using
      three different methods. The methodology based on a dynamic calibration test
      along with a nonlinear regression analysis produced the best results. The
      coefficient of determination comparing the dynamometer model output to the
      measured angular velocity and torque was 0.999 for a ramp input and 0.989 for a
      sinusoidal input. The inertia and resistance were determined for the rollers and
      the wheelchair wheels. The calculation of the electro-mechanical parameters
      allows for the complete description of the propulsive torque produced by an
      individual, given only the angular velocity and acceleration. The measurement of
      the electro-mechanical properties of the dynamometer as well as the
      wheelchair/human system provides the information necessary to simulate real-world
      conditions.

PMID- 11322471
TI  - A comparison of methods to compute the point of force application in handrim
      wheelchair propulsion: a technical note.
AB  - Several methods are available for computing the location of the point of force
      application (PFA) in manual wheelchair propulsion using kinetic data. We compared
      five different techniques for computing the PFA location in analysis of data from
      five wheelchair users propelling their own wheelchairs using their normal
      propulsion style. The effects of the assumptions used in the calculations on the
      resulting location of the PFA, handrim force and moment components, and
      mechanical efficiency (e) were quantified. When kinetic data were used to locate
      the PFA, the most consistent and stable results were obtained using the
      assumptions that components of the handrim moment about the anteriorly directed
      and vertically directed axes were negligible. Some assumptions led to unsolvable
      equations at points during the propulsion cycle, demonstrating that they were
      inappropriate. All PFA values calculated with kinetic data were unstable at the
      beginning and end of the propulsion phase. While differences exist due to
      individual technique, assuming handrim moment components about the anterior
      posterior, vertical, and/or both axes resulted in the most representative
      results.

PMID- 11322472
TI  - The effect of treadmill training on the ambulation of stroke survivors in the
      early stages of rehabilitation: a randomized study.
AB  - The objective of this study was to compare the effects of conventional over
      ground gait training with treadmill training on the restoration of gait in people
      with hemiparesis following a stroke. Twenty-five individuals in the early stages
      of rehabilitation were alternately assigned to one of two treatment groups. In
      addition to conventional physical therapy, the experimental group participated in
      15 treadmill-training sessions in which a handrail was used for external support.
      The control group received the same number of equal length sessions of over
      ground ambulation. Treatment effects were established by pre- and posttreatment
      assessment of: 1) functional walking ability, 2) walking speed, 3) stride length,
      4) temporal characteristics of gait, and 5) electromyographic activity of calf
      muscles. Normal values were obtained from eight healthy individuals of
      approximately the same age as the stroke survivors. The study demonstrates that
      individuals following a stroke are well able to tolerate treadmill training in
      the early stage of their rehabilitation process without the use of a weight
      support apparatus. Furthermore, the findings suggest that treadmill training may
      be more effective than conventional gait training for improving some gait
      parameters such as functional ambulation, stride length, percentage of paretic
      single stance period, and gastrocnemius muscular activity.

PMID- 11322473
TI  - Effect of endurance training program based on anaerobic threshold (AT) for lower
      limb amputees.
AB  - We have already reported that the one-leg cycling test driven by the subject's
      sound leg as the exercise load test is effective in measuring the anaerobic
      threshold (AT) of unilateral lower limb amputees. The aim of this research is to
      investigate whether or not endurance training based on each subject's AT gained
      from the one-leg cycling test is useful in improving the physical fitness of
      lower limb amputees. The test subjects were all unilateral transfemoral amputees
      comprising a group of 14 undertaking endurance training and a control group of
      10. The form of endurance training is driving an ergometer with the sound limb
      only in the same way as the load test. The training program was designed so that
      the subjects would exercise at a target heart rate corresponding to AT point for
      30 minutes per day, 3-5 days each week for 6 weeks. After the training periods,
      in the training subjects the AT and maximum oxygen uptake (__O2max) increased
      significantly. The rate of increase averaged 36.5%, 26.0%, respectively, compared
      to their levels before the training. On the contrary, no changes occurred in the
      control subjects. These results suggest that our chosen training program based on
      each subject's AT is effective in improving the physical fitness of lower limb
      amputees.

PMID- 11322474
TI  - Development of an exercise expert system for older adults.
AB  - The purpose of this study was to develop a computerized exercise expert system
      (CEES) that creates tailored exercise plans for older adults. A panel of experts
      was selected in the areas of medicine, exercise physiology, health promotion,
      exercise psychology, and gerontology. The experts communicated with the principal
      investigator and the project members by mail, email, telephone, and expert
      meetings. A two-day workshop was held during the second year for the project
      members as well as local and national experts to review the CEES. The CEES
      demonstrated adequate inter-rater reliability (0.80) and criterion validity
      (0.70). Content validity was achieved by literature review and expert opinion.
      The CEES gathers information on the elder's health status, clinical factors, and
      exercise determinants that characterize specific barriers or incentives to
      exercise. The software program then develops individualized exercise
      prescriptions that are customized to older adults.

PMID- 11322475
TI  - The spasticity evaluation test (SeT): a pilot study.
AB  - This paper addresses the development of an apparatus designed to evaluate
      clinically the presence of spasticity affecting the elbow. The biomechanical
      contributions due to the lever-arm muscles and to the gravity force are accounted
      for using software algorithms that express gravity force and lever arm as
      functions of the elbow angle and are able to provide information on the force
      exerted by the muscles at a known speed. The preliminary data indicate that the
      device can be applied easily in the clinical setting. Further studies are
      required to demonstrate conclusively the validity and reliability of this device
      in quantifying spasticity at the elbow.

PMID- 11322476
TI  - Rehabilitation for the 21st Century.

PMID- 11322477
TI  - Restoration of function: current challenges and future opportunities through
      electrical stimulation.

PMID- 11322478
TI  - Low vision and blindness.

PMID- 11322479
TI  - Recent progress in lysosomal alpha-mannosidase and its deficiency.
AB  - Lysosomal alpha-mannosidase (EC 3.2.1.24) is a major exoglycosidase in the
      glycoprotein degradation pathway. A deficiency of this enzyme causes the
      lysosomal storage disease, alpha-mannosidosis, which has been described in
      humans, cattle, domestic cats and guinea pigs. Recently, great progress has been
      made in studying the enzyme and its deficiency. This includes cloning of the gene
      encoding the enzyme, characterization of mutations related to the disease,
      establishment of valuable animal models, and encouraging results from bone marrow
      transplantation experiments.

PMID- 11322480
TI  - Post-transcriptional control of c-erb B-2 overexpression in stomach cancer cells.
AB  - The growth factor receptor oncogene, c-erb B-2, is frequently overexpressed in
      the adenocarcinomas of breast, ovary, lung and stomach. Although the mechanism of
      erb B-2 overexpression is thought as the result of transcriptional upregulation
      in many primary human carcinomas, expression rate of c-erb B-2 at mRNA level is
      usually lower than the level of translated protein. We also found that the
      expression of erb B-2 in SNU-1 stomach cancer cells was greater at post
      transcription level (Bae et al., 1993). To explore the underlying mechanism of
      erb B-2 protein overexpression, we have chosen two cells lines, SNU-1 and SNU-16
      where transcription rate of erb B-2 was closely resemble to each other while
      expressed protein levels were quite different. The synthesis rate of erb B-2
      protein in SNU-1 cells was faster than SNU-16 cells while levels of erb B-2 mRNA
      were found to be similar in both cell lines. The half-life of the expressed erb B
      2 protein was not significantly different in both cell lines. Analysis of the 5'
      untranslated region (UTR) of erb B-2 mRNA (-1approximately-323) showed no
      sequence abnormality in both cell lines. However, ribonuclease protection assay
      using cloned 5 UTR sequence revealed that the size of 5' UTR of erb B-2 mRNA
      which associate with transcription initiation site(s) in SNU-1 cells was longer
      than that in SNU-16. These results suggest that the increased erb B-2 protein
      synthesis rate possibly due to the redundant selection of transcription
      initiation might be a mechanism of erb B-2 overexpression in SNU-1 cells.

PMID- 11322481
TI  - L-ergothioneine level in red blood cells of healthy human males in the Western
      province of Saudi Arabia.
AB  - Ergothioneine is widely distributed in biological systems, particularly in red
      blood cells of animals. However, it's functional role in human body is not well
      understood. In order to investigate the biochemical effect of L-ergothioneine,
      its concentration changes in human blood with respect to ages in healthy
      individuals was first investigated. L-ergothioneine concentrations in the blood
      of Saudi males from western province at different stages of life were measured by
      the procedure of Carlsson et al., 1974. At early stages of life (1-10 years), the
      concentrations of LER is 1.5-2.0 mg/100 ml. It increases gradually at the age of
      11-18 years where it reaches the maximum value of 3.7 mg/100 ml. Then, it
      declines gradually to 3.0-2.3 mg/ 100 ml during the period of 19-50 years. An
      increase in the level of LER (2.8 mg/100 ml) was seen at the age of 51+.

PMID- 11322482
TI  - Arylamine N-methyltransferase and thiol methyltransferase activities in
      cholestatic rat liver induced by common bile duct ligation.
AB  - Methylation catalyzed by methyltransferases is a major metabolic pathway for an
      inactivation of some catecholamines, niacinamide as well as aliphatic sulfhydryl
      drugs and toxic hydrogen sulfides. To investigate the effects of obstructive
      jaundice in an animal model, common bile duct ligation (CBDL) was performed in
      the rat and enzyme activities of S-adenosyl-L-methionine-dependent arylamine N
      methyltransferase and thiol methyltransferase were examined in liver cell
      fractions and serum for a period of 42 d after CBDL. Both mitochondrial and
      microsomal arylamine N-methyltransferase showed significant increases in their
      activities between the 1st through the 7th day (P < or = 0.05 to 0.001), and
      between the 1st through the 28th day (P < or = 0.01 to 0.001) post-ligation,
      although the cytosolic arylamine N-methyltransferase activity did not show a
      significant change compared to the activities from the sham-operated control. The
      mitochondrial as well as microsomal thiol methyltransferase showed significant
      increases in their activities between the 1st through the 28th day (P < or = 0.05
      to 0.01 and P < or = 0.01 to 0.001, respectively) post-ligation, although the
      cytosolic thiol methyltransferase activity did not show a significant change
      compared to the activities from the sham-operated control. Arylamine N
      methyltransferase and thiol methyltransferase in the serum from cholestatic rats
      also showed significant increases in their activities between the 1st through
      28th day (P < or = 0.01 to 0.001), and between the 0.5th through the 42nd day (P
      < or = 0.05 to 0.001) post-ligation compared to the sham-operated control,
      respectively. Enzyme kinetic parameters (Km and Vmax) of hepatic membrane-bound
      arylamine N-methyltransferase and thiol methyltransferase were analyzed with the
      preparation from the 7th day post-ligation, using tryptamine or 4
      chlorothiophenol as substrates and S-Adenosyl-L-[methyl-3H]methionine as co
      substrate. The results indicate that although the Km values were about the same
      as the sham-operated control, the Vmax values of both enzymes increased
      significantly (P < or = 0.01 and 0.001, respectively). These results suggest that
      the biosynthesis of arylamine N-methyltransferase and thiol methyltransferase
      have been induced in response to obstructive jaundice.

PMID- 11322483
TI  - F508 amino acid deletion mutation of CFTR gene in Korean lung cancer patients.
AB  - Mutations of the transmembrane conductance regulator (CFTR) gene in cystic
      fibrosis lead to dysfunction of the lung, pancreas, and sweat glands, etc. To
      investigate the possibility of the relationship between lung cancer and the
      mutations of CFTR gene, we determined amino acid sequences using reverse
      transcription-polymerase chain reaction (RT-PCR) and DNA sequencing. In this
      study, the deletion mutation of 508th amino acid in one of nine lung caner
      patients was found confirming that CFTR gene mutation exists in a Korean lung
      cancer patient.

PMID- 11322484
TI  - Effect of metal ions on the stability of metallothionein in the degradation by
      cellular fractions in vitro.
AB  - Metallothioneins (MT), small molecular weight metal binding proteins are known to
      play an important protective role against heavy metal toxicity, either as
      antioxidants or pre-oxidants. However, the mode of metabolic fate of MTs in
      various metal complexes is not clearly understood. This study was carried out to
      better understand the mode of selective turnover rate of various form of MT in
      complexes with different metals. The degradation of in vitro translated mouse 35S
      cysteine-MT was examined in lysosomal or cytosolic fractions from mouse liver by
      gel electrophoresis and autoradiography. Overnight incubations of MT showed
      extensive proteolysis in the lysosomal fraction but not in cytosolic fractions.
      However, Cu2+-MT was found to be stable under the same experimental condition. In
      contrast, Zn did not interfere with MT degradation. These results suggest that
      lysosomes are chiefly responsible for MT removal and appears to be selective on
      the metals involved in the MT complex. In vitro, translated, radiolabeled MT
      provides a suitable substrate for investigating the characteristics of MT
      degradation.

PMID- 11322485
TI  - Adaptation of cAMP signaling system in SH-SY5Y neuroblastoma cells following
      expression of a constitutively active stimulatory G protein alpha, Q227L Gsalpha.
AB  - Heterotrimeric GTP-binding proteins (G protein) are known to participate in the
      transduction of signals from ligand activated receptors to effector molecules to
      elicit cellular responses. Sustained activation of cAMP-G protein signaling
      system by agonist results in desensitization of the pathway at receptor levels,
      however it is not clear whether such receptor responses induce other changes in
      post-receptor signaling path that are associated with maintenance of AMP levels,
      i.e. cAMP-forming adenylate cyclase (AC), cAMP-degrading cyclic nucleotide
      phosphodiesterase (PDE) and cAMP-dependent protein kinase (PKA). Experiments were
      performed to determine the expression of AC, PDE, and PKA isoforms in SH-SY5Y
      neuroblastoma cells, in which cAMP system was activated by expressing a
      constitutively activated mutant of stimulatory G protein (Q227L Gsalpha).
      Expression of ACI mRNA was increased, but levels of ACVIII and ACIX mRNA were
      decreased. All of the 4 expressed isoforms of PDE (PDE1C, PDE2, PDE 4A, and
      PDE4B) were increased in mRNA expression; the levels of PKA RIalpha, RIbeta, and
      RIIbeta were increased moderately, however, those of RIIalpha and Calpha were
      increased remarkably. The activities of AC, PDE and PKA were also increased in
      the SH-SY5Y cells expressing Q227L Gsalpha. The similar changes in expression and
      activity of AC, PDE and PKA were observed in the SH-SY5Y cells treated with
      dbcAMP for 6 days. Consequently, it is concluded that the cAMP system adapts at
      the post-receptor level to a sustained activation of the system by differential
      expression of the isoforms of AC, PDE, and PKA in SH-SY5Y neuroblastoma. We also
      showed that an increase in cellular cAMP concentration might mediate the observed
      changes in the cAMP system.

PMID- 11322486
TI  - Combination treatment for osteosarcoma with baculoviral vector mediated gene
      therapy (p53) and chemotherapy (adriamycin).
AB  - The insect baculovirus Autographa californica multiple nuclear polyhedrosis virus
      (AcMNPV) has been evaluated as a vector for gene delivery to human tumor cells. A
      human osteogenic sarcoma cell line, Saos-2, was found to be highly susceptible to
      infection with a baculoviral vector, with nearly 100% of Saos-2 cells being able
      to express a lacZ reporter gene after a brief exposure to the virus at a m.o.i.
      of 30 pfu/cell. The production of beta-galactosidase protein was 18-times greater
      than that in HepG2 cells which were previously thought to be the mammalian cells
      most susceptible to the baculovirus. The possibility of developing a baculovirus
      as a cytotoxic vector for p53-defective cancer was tested by destruction of Saos
      2 cells (p53-/-) with a recombinant baculovirus containing the wild type p53 gene
      (BV-p53) in vitro. The p53 baculovirus induced apoptotic cell death in tumor
      cells in a dose-dependent manner with approximately 60% killing at an m.o.i. of
      160 pfu/cell. Combined treatments of gene therapy (p53) and chemotherapy
      (adriamycin) resulted in synergistic and potent killing of the osteogenic sarcoma
      cells. For example, greater than 95% of Saos-2 cells were killed by the
      combination of BV-p53 (m.o.i. of 100) and adriamycin (35 ng/ml), whereas
      approximately 50% and approximately 55% cells were killed by BV-p53 and
      adriamycin alone, respectively. These results indicate that a baculoviral gene
      delivery vector can be used to efficiently target certain types of mammalian
      cells and the combination treatment of gene-therapy mediated by a baculovirus and
      chemotherapy may enhance induction of apoptosis in cancer cells.

PMID- 11322487
TI  - Regulation of GTP-binding state in RalA through Ca2+ and calmodulin.
AB  - RalA GTPase, a member of Ras superfamily proteins, shows alternative forms
      between the active GTP-binding and the inactive GDP-binding states. Ral-specific
      guanine nucleotide exchange factor such as RalGDS interacts with activated Ras
      and cooperates with Ras indicating that Ral can be activated through Ras
      signaling pathway. Another activation path for Ral are through Ca2+-dependent but
      Ras-independent manner. In this study, studies were carried out to examine
      possible effects of Ca2+ and calmodulin, Ca2+-binding protein, directly on the
      GTP/GDP-binding state to recombinant unprenylated GST-RalA proteins. The results
      showed that Ca2+ stimulated the binding of GTP to RalA, whereas it reduced the
      binding of GDP to RalA. However, it does not involve a high affinity association
      of Ca2+ with RalA. Ca2+/calmodulin stimulated the GTPase activity of RalA. These
      results indicate that Ca2+ alone activates RalA by stimulating GTP-binding to
      RalA and Ca2+/calmodulin inactivates RalA by increasing the activity of
      RalGTPase.

PMID- 11322488
TI  - Detection of circulating tumor cells in patients with gastrointestinal tract
      cancer using RT-PCR and its clinical implications.
AB  - To investigate the relationship between the presence of circulating tumor cells
      in different stages of gastrointestinal tract cancer and the subsequent relapse
      or distant metastasis, circulating levels of CEA mRNA was serially examined at an
      interval of 10.6+/-4.5 or 13.7+/-3.0 months in gastric or colorectal cancer
      patients, respectively. CEA mRNA was measured by means of RT-PCR amplification as
      an indicator for micrometastatic malignant cells. Seven of twenty-nine
      respectable gastric cancer patients (24.1%) [EGC: 2/9 (22.2%), AGC IIIa: 1/5
      (20.0%), AGC IIIb: 4/15 (26.6%)] were positive for CEA mRNA on the initial test
      and 10 of 29 patients (34.4%) [EGC: 2/ 9 (22.2%), AGC IIIa: 1/5 (20.0%), AGC
      IIIb: 7/15 (46.7%)] were positive on a follow-up test. Only in AGC IIIb, the
      positive rate for CEA mRNA increased about twice and 6 of 7 positive cases
      (85.7%) relapsed within 2.6+/-2.4 months after the follow-up test. In colorectal
      cancer, 4 of 19 patients (21.1%) [B2: 1/6 (16.7%), C2: 3/13 (23.0%)] were
      positive on the initial test and 10 of 19 patients (52.6%) [B2: 4/6 (66.7%), C2:
      6/13 (46.2%)] were positive on a follow-up test showing an increase in positive
      rates during a follow-up, however, no significant correlation between CEA mRNA
      positivity and subsequent relapse was demonstrated. These results suggest that an
      early tumor cell dissemination may occur in gastrointestinal tract cancer without
      subsequent relapse, however, the serial regular examination of CEA mRNA level may
      contribute to predicting a subsequent relapse in AGC IIIb in gastric cancer.

PMID- 11322490
TI  - Presence of ghrelin in normal and adenomatous human pituitary.
AB  - Recently, an endogenous ligand has been described for the growth hormone
      secretagogue receptor (GHS-R), named ghrelin. It was originally isolated from the
      stomach, but it is also present in the hypothalamus, where the highest
      concentration of GHS-R has been detected. It is well established that synthetic
      GHSs exert their effects on the growth hormone (GH) axis principally via the
      hypothalamus, although they are also able to stimulate GH release directly from
      the pituitary. We have previously demonstrated the presence of GHS-R mRNA
      expression in normal and abnormal human pituitary. We have therefore now
      investigated the expression of the newly recognized endogenous ligand in rat as
      well as in human pituitary. We readily detected ghrelin mRNA message in normal
      rat pituitary using reverse transcriptase polymerase chain reaction with
      published primers. We then designed primers to the corresponding region on the
      human ghrelin sequence and successfully detected mRNA message in normal human
      pituitary, as well as in somatotroph, lactotroph, corticotroph, thyrotroph, and
      nonfunctioning adenomas. We confirmed the expected polymerase chain reaction
      product by direct sequencing. In conclusion, we suggest that in addition to the
      probable hypothalamic effects of ghrelin, the peptide is synthesized locally
      within the pituitary gland, where it may influence the release of GH in an
      autocrine or paracrine manner.

PMID- 11322489
TI  - Growth hormone secretagogues and hypothalamic networks.
AB  - Growth hormone secretagogues (GHSs) act at distinct levels to control growth
      hormone (GH) secretion. At the pituitary level they reinforce or extend a tonic
      GH-releasing-hormone (GHRH)-induced activated state by mobilizing intracellular
      Ca2+ store. At the hypothalamic level GHS actions are more complex than
      originally anticipated. Chronic treatments with GHS result in loss of
      responsiveness to the secretagogues, an effect probably accounted for by indirect
      negative feedback of GHS stimulated plasma GH levels over GHRH release. Moreover,
      intracerebroventricular treatments with GHS can have paradoxical, inhibitory
      effects on GH secretion. Several mechanisms can account for such dual effects.
      GHS receptors were found to extend far beyond the arcuate nucleus and are mainly
      coexpressed by GHRH, somatostatin, and neuropeptide Y (NPY) neurons. Activation
      of GHRH neurons by GHS can be direct or indirect. Indeed using antisense strategy
      we found that sstl are physiological activators of arcuate GHRH neurons and we
      propose that activation of SRIH arcuate interneurons by GHS can increase GHRH
      neuron activity. Moreover, GHS can stimulate distinct populations of NPY neurons
      having opposite effects on GH secretion: arcuate NPY interneurons, act as
      indirect facilitators of GHRH release, whereas, on the contrary, a different
      subset of NPY neurons projecting to the periventricular hypothalamus (those also
      involved in mediating leptin effects on GH) seems able to activate SRIH release.

PMID- 11322491
TI  - Growth hormone-independent cardiotropic activities of growth hormone-releasing
      peptides in normal subjects, in patients with growth hormone deficiency, and in
      patients with idiopathic or ischemic dilated cardiomyopathy.
AB  - Growth hormone releasing peptides (GHRPs) are synthetic molecules endowed with
      potent neuroendocrine activities mediated by specific receptors in the pituitary
      and in the central nervous system. GHRPs receptors have been reported even in
      perpheral tissues, particularly in the myocardium, where they probably mediate
      growth hormone (GH)-independent activities. We studied in humans the cardiac
      effects of hexarelin administration in 7 normal adults, in 7 severe GH-deficient
      patients, and in 12 patients with severe dilated cardiomyopathy. Left ventricular
      ejection fraction (LVEF), mean blood pressure (MBP), heart rate (HR), and GH
      levels were evaluated at baseline and every 15 min up to 60 min after acute 2.0
      microg/kg iv hexarelin administration. Basal LVEF in dilated cardiomyopathy was
      impaired and lower (p < 0.001) than in GH deficiency, in turn lower (p< 0.001)
      than in normal subjects. Hexarelin signficantly (p < 0.05) increased LVEF in
      normal and in GH-deficient subjects, but not in dilated cardiomyopathy, without
      significant variations in MBP and HR. Hexeralin significantly (p < 0.05)
      increased GH levels in normal subjects and in dilated cardiomyopathy but not in
      GH deficiency. These findings suggest that, in humans, the acute administration
      of hexarelin exerts a GH-independent positive inotropic effect likely mediated by
      specific GHRPs myocardial receptors.

PMID- 11322492
TI  - Hexarelin, but not growth hormone, protects heart from damage induced in vitro by
      calcium deprivation replenishment.
AB  - The effects of hexarelin, a growth hormone (GH) secretagogue, and human GH on the
      mechanical and metabolic changes measured in isolated rat hearts submitted to 5
      min of Ca2+ deprivation followed by reperfusion with Ca2+-containing medium, the
      so-called calcium paradox phenomenon, were studied. Hexarelin (80 microg/kg bid,
      subcutaneously) administered for 7 d to male rats effectively antagonized the
      sudden increase in resting tension measured in vitro on Ca2+ repletion. Moreover,
      during Ca2+ repletion the release of creatine kinase activity (an index of cell
      damage) in the perfusate of these hearts was reduced up to 40% compared with
      controls. By contrast, administration of hexarelin for 3 d or GH (400 microg/kg
      bid, subcutaneously) for 7 d did not affect the mechanical and metabolic
      alterations induced by the calcium paradox. To assess its direct and acute
      cardiac effects, hexarelin (8 microg/mL) was perfused in vitro in recirculating
      conditions for 60 min through the hearts of normal rats. In this case, hexarelin
      did not stimulate heart contractility and failed to prevent ventricular
      contracture upon Ca2+ readmission, whereas diltiazem, a Ca2+channel blocker,
      effectively antagonized the calcium paradox phenomenon. We conclude that short
      term in vivo exposure to hexarelin, but not GH, enables cardiac myocyites to
      prevent cytoplasmatic electrolytic unbalance and to control intracellular Ca2+
      gain, two functions largely impaired during the calcium paradox phenomenon.
      Moreover, because the effect of hexarelin is not acute but dependent on the
      length of in vivo treatment, we suggest that it requires modifications of
      myocardiocyte physiology.

PMID- 11322493
TI  - Hexarelin protects H9c2 cardiomyocytes from doxorubicin-induced cell death.
AB  - Growth hormone secretagogues (GHSs) are synthetic peptidyl and nonpeptidyl
      molecules that possess strong growth hormone-releasing activity acting on
      specific pituitary and hypothalamic receptor subtypes. Differently from
      nonpeptidyl GHSs, peptidyl molecules such as hexarelin, a hexapeptide, possess
      specific high-affinity binding sites in animal and human heart and, after
      prolonged treatment, protect rats in vivo from ischemia-induced myocardial
      damage. To verify the hypothesis that peptidyl GHSs protect heart cells from cell
      death, we have investigated the cellular effects of hexarelin on H9c2
      cardiomyocytes, a fetal cardiomyocyte-derived cell line, and on Hend, an
      endothelial cell line derived from transformed murine heart endothelium. We show
      that (i)H9c2 cardiomyocytes show specific binding for 125I-Tyr-Ala-hexarelin,
      which is inhibited by peptidyl GHSs such as Tyr-Ala-hexarelin and hexarelin but
      not by the nonpeptidyl GHS MK-0677, (ii) hexarelin promotes survival of H9c2
      cardiomyocytes induced to die by doxorubicin, and (iii) that hexarelin inhibits
      apoptosis, as measured by DNA fragmentation, induced in both H9c2 myocytes and
      endothelial cells. In conclusion, our findings show that peptidyl GHSs such as
      hexarelin act as survival factors for cardiomyocytes and endothelium-derived
      cells in culture. These findings suggest that the inhibitory activity of
      hexarelin on cardiomyocytes and endothelial cell death could explain, at least
      partially, its cardioprotective effect against ischemia recorded in rats in vivo.

PMID- 11322494
TI  - Preclinical pharmacology of CP-424,391, an orally active pyrazolinone-piperidine
      [correction of pyrazolidinone-piperidine] growth hormone secretagogue.
AB  - Growth hormone secretagogues (GHSs) represent attractive therapeutic alternatives
      to recombinant growth hormone (GH), given their ability to amplify pulsatile
      hormone secretion in a relatively physiologic manner. CP-424,391 (391) is a
      novel, orally active pyrazolinone-piperidine [corrected] GHS. In rat pituitary
      cell cultures, 391 stimulated GH release with an EC50 = 3 nM. The addition of 391
      to rat pituitary cells activated intracellular calcium signaling but did not
      elevate intracellular cyclic adenosine monophosphate (cAMP). 391 also modulated
      the effects of GH-releasing hormone and somatostatin on pituitary cell GH-release
      and intracellular signaling. In nonpituitary cell lines, the ability of 391 to
      stimulate intracellular signaling was dependent on the expression of recombinant
      human GHS receptor. Acute administration of 391 to anesthetized rats or to
      conscious dogs induced pulsatile release of G H in a dose-dependent manner.
      Plasma insulin-like growth factor-I (IGF-I) was elevated progressively over a 5-d
      course of daily oral dosing in dogs. Chronic oral administration of 391 augmented
      body weight gain in rats and dogs. Thus, the peptidomimetic GHS 391 has potential
      utility for the treatment of clinical conditions that could benefit from systemic
      augmentation of GH and IGF-I levels.

PMID- 11322495
TI  - Do growth hormone-releasing peptides act as ghrelin secretagogues?
AB  - NN703 is an orally active and selective growth hormone secretagogue (GHS) that
      was derived from growth hormone-releasing peptide-1(GHRP-1) via ipamorelin by a
      peptidomimetic approach and has now entered into phase II clinical trials. When
      the disposition in rats of NN703 and GHRP-6 was studied using whole-body
      autoradiography following administration of an iv dose of radiolabeled material,
      we found that a substantial amount of these secretagogues accumulate in the
      glandular part of the stomach. Because this is the site of synthesis and
      secretion of ghrelin, the endogenous GHS, we investigated the effect of resection
      of the gastrointestinal (GI) tract on growth hormone (GH) release induced by GHRP
      6. This procedure significantly attenuated the GH secretion response by 60-70%.
      By contrast, the effect of GH-releasing hormone on GH release was not inhibited.
      The binding of GHRPs to the glandular part of the stomach and the blunted GH
      response to GHRP-6 following resection of the GI tract suggest a role for ghrelin
      as a mediator of part of the GH-releasing effect of GHRPs.

PMID- 11322497
TI  - Central actions of the nonpeptide growth hormone secretagogue GHS-25.
AB  - Growth hormone secretagogues (GHSs) increase the activity of hypothalamic arcuate
      nucleus neurons thought to be involved in controlling the release of growth
      hormone (GH). The GHS receptor is also found in hypothalamic regions not
      associated with the release of GH, suggesting that GHSs may influence other
      hypothalamic systems. This study utilized double-labeling immunocytochemical
      techniques to examine the hypothalamic actions of a novel nonpeptide GHS, GHS-25.
      In common with other GHSs, GHS-25 induced significant amounts of Fos
      immunoreactivity in the arcuate nucleus of conscious male rats. However, unlike
      other GHSs, GHS-25 also induced Fos immunoreactivity in the supraoptic nucleus.
      Double labeling revealed that approx 66% of supraoptic nucleus cells that were
      Fos positive after the administration of GHS-25 were also immunoreactive for
      oxytocin. Thus, in addition to its actions on the GH axis, GHS-25 may influence
      the release of neurohypophyseal hormone.

PMID- 11322496
TI  - Recombinant human GHRH(1-44)NH2: clinical utility and therapeutic development
      program.
AB  - Growth hormone (GH) secretagogues are becoming increasingly attractive
      alternatives to GH or insulin-like growth factor-I (IGF-I) for the treatment of
      conditions that may benefit from activation of the GH/IGF-I axis. This stems from
      the realization that (1) GH secretagogues stimulate the pulsatile release of
      endogenous GH; (2) feedback control of endogenous GH and IGF-I is preserved,
      guarding against imbalances between GH and IGF-I levels; and (3) GH treatment is
      associated with adverse effects in the elderly. Of the GH secretagogues, growth
      hormone-releasing hormone (GHRH) remains the best characterized, in terms of
      identity of the ligand-receptor pair and its exclusive somatotropic activity at
      the level of the pituitary. Full-length natural GHRH (1-44) amide can now be
      produced by recombinant technologly on a commercially viable scale, and is
      currently being evaluated in early phase clinical trials. The purpose of these
      studies is to evaluate the efficacy and tolerability of chronic subcutaneous
      administration of GHRH over a range of doses in elderly subjects. Therapeutic
      areas that are being investigated in the elderly include congestive heart
      failure, osteoporosis, and improvements in body composition and function in the
      frail elderly.

PMID- 11322498
TI  - Interactions of growth hormone secretagogues and growth hormone-releasing
      hormone/somatostatin.
AB  - The class of novel synthetic compounds termed growth hormone secretagogues (GHSs)
      act in the hypothalamus through, as yet, unknown pathways. We performed
      physiologic and histochemical studies to further understand how the GHS system
      interacts with the well-established somatostatin (SRIF)/growth hormone-releasing
      hormone (GHRH) neuroendocrine system for regulating pulsatile GH secretion.
      Comparison of the GH-releasing activities of the hexapeptide growth hormone
      releasing peptide-6 (GHRP-6) and GHRH administered intravenously to conscious
      adult male rats showed that the pattern of GH responsiveness to GHRP-6 was
      markedly time-dependent, similar to that observed with GHRH. Immunoneutralization
      of endogenous SRIF reversed the blunted GH response to GHRP-6 at trough times,
      suggesting that GHRP-6 neither disrupts nor inhibits the cyclical release of
      endogenous hypothalamic SRIF. By striking contrast, passive immunization with
      anti-GHRH serum virtually obliterated the GH responses to GHRP-6, irrespective of
      the time of administration. These findings suggest that the GHSs do not act by
      altering SRIF release but, rather, stimulate GH release via GHRH-dependent
      pathways. Our dual chromogenic and autoradiographic in situ hybridization
      experiments revealed that a subpopulation of GHRH mRNA-containing neurons in the
      arcuate (Arc) nucleus and ventromedial nucleus (VMN) of the hypothalamus
      expressed the GHS receptor (GHS-R) gene. These results provide strong anatomic
      evidence that GHSs may directly stimulate GHRH release into hypophyseal portal
      blood, and thereby influence GH secretion, through interaction with the GHS-R on
      GHRH- containing neurons. Altogether, these findings support the notion that an
      additional neuroendocrine pathway may exist to regulate pulsatile GH secretion,
      possibly through the influence of the newly discovered GHS natural peptide,
      ghrelin.

PMID- 11322499
TI  - Somatostatin octapeptides (lanreotide, octreotide, vapreotide, and their analogs)
      share the growth hormone-releasing peptide receptor in the human pituitary gland.
AB  - The binding affinity of somatostatin-14 (SRIF), various SRIF derivatives, and
      some peptides belonging to the growth hormone-releasing peptide (GHRP) family to
      specific receptors for SRIF and GHRP in the human pituitary gland has been
      measured. GHRP receptors have been identified using [125I]Tyr-Ala-hexarelin, a
      peptide that thas been demonstrated to be a potent growth hormone (GH) releaser
      in humans. Tyr-Ala-hexarelin binding was displaced in a dose-dependent manner by
      different GHRPs (hexarelin, GHRP-2, and EP-51216). Surprisingly, some SRIF
      octapeptide derivatives such as vapreotide, lanreotide, octreotide, and their
      analogs were also able to displace the GHRP ligand. By contrast, no inhibition of
      Tyr-Ala-hexarelin binding was observed in the presence of SRIF or SRIF
      derivatives (SRIF H-2186, H-2485, and H-3382) that are known to have a weak SRIF
      like activity. When [125I]Tyr1-SRIF-14 was used as a ligand, we observed
      displacement with SRIF and the octapeptide SRIF analogs but not with GHRPs and
      other SRIF derivatives. The results point to a sharing of the GHRP receptor with
      the octapeptide SRIF analogs, but not SRIF. Our data are consistent with the
      hypothesis that the putative natural GH secretagogue ligand may be a growth
      hormone release inhibiting factor that is different from SRIF and that is
      antagonized by GHRP.

PMID- 11322500
TI  - Growth hormone-releasing hormone and growth hormone secretagogue-receptor
      ligands: focus on reproductive system.
AB  - Growth hormone-releasing hormone (GHRH) and somatostatin are the most important
      hypothalamic neurohormones controlling growth hormone (GH) secretion. Several
      neurotransmitters and neuropeptides also play an important role in the control of
      GH secretion, mainly acting via modulation of GHRH and somatostatin. In the past
      two decades, particular attention has been given to a new family of substances
      showing a strong GH-releasing effect: GH secretagogues (GHSs). GHSs increase GH
      secretion in a dose- and age-related manner after iv and even oral
      administration. The endocrine effects of GHSs, are not fully specific for GH;
      they show, in fact, prolactin- (PRL), adenocorticotropic hormone- and cortisol
      releasing effects. Specific GHS receptors are present in both the central nervous
      system and peripheral tissues, where they mediate several extraendocrine effects
      of GHSs. The isolation of these "orphan" receptors suggested the existence of an
      endogenous GHS-like ligand that could be represented by a recently discovered
      gastric peptide, named ghrelin. The interaction between GHSs and GHRH at the
      central level and in the pituitary gland, but not at peripheral level, has
      clearly been shown. Because GHRH and GHS receptors share the same localization in
      some peripheral tissues, they may have some interactions even at this level.

PMID- 11322502
TI  - Effects of growth hormone and its secretagogues on bone.
AB  - The growth hormone (GH)/insulin-like growth factor-1 axis is not only of
      importance for linear body growth during childhood, but it is also one of the
      major determinants of adult bone mass. Studies show that GH treatment increases
      bone mass in rodents as well as in adult GH-deficient humans, but the effect of
      GH treatment on bone mass in healthy humans has so far not been impressive.
      Recently, a new class of GH secretagogues (GHSs) has been developed. In humans,
      GHS treatment affects biochemical markers of bone turnover and increases growth
      velocity in selected short children with or without GH deficiency. In rodents,
      GHS treatment increase bone mineral content, but it has not yet been shown that
      GHS treatment can affect bone mass in adult humans.

PMID- 11322503
TI  - Synthetic growth hormone secretagogues control growth hormone secretion in the
      chicken at pituitary and hypothalamic levels.
AB  - In the chicken growth hormone (GH) secretion is predominantly controlled by two
      hormones, thyrotropin-releasing hormone (TRH) and somatostatin (SRIH),
      respectively stimulating and inhibiting GH release. In view of the hypothesis of
      a novel GH secretagogue (GHS) in mammals, this specific species was used to
      further assess the exact function of two nonpeptidyl GHSs-L-692,429 and L
      163,255. Both synthetic products stimulate GH secretion directly at the level of
      the pituitary as shown in in vitro perifusion studies. Plasma GH levels increase
      within 10-15 min after a single challenge of L-692,429 or L-163,255. A SRIH
      pretreatment dimishes this GH response. Both GH-releasing peptide mimetics
      decrease hypothalamic TRH concentrations, whereas SRIH levels are not affected.
      The novel GHS may therefore control GH secretion both at the level of the
      pituitary and the hypothalamus. The present article shows that nonpeptidyl
      mimetics also control GH secretion in nonmammalian species suggesting that the
      endogenous hormone may be a conserved GH stimulator in several vertebrates. The
      GH response to GHS in birds may be regulated both directly at the level of the
      pituitary and by releasing another endogenous GH stimulator (TRH) from the
      hypothalamus.

PMID- 11322504
TI  - The in vitro effect of leptin on growth hormone secretion from primary cultured
      ovine somatotrophs.
AB  - Although existing data suggest an influence of leptin on circulating levels of
      growth hormone (GH), the action site and properties of leptin are still
      controversial. Using primary cultured ovine pituitary cells, we studied the
      direct effect of leptin on the secretion of GH. Pituitary cells were dissociated
      by collagenase and subjected to Percoll gradient centrifugation to enrich the
      somatotroph population to 60-80% of cells. Treatment of primary cultured ovine
      somatotrophs with leptin (10(-9)-10(-7) M) for 30 min did not affect basal, GH
      releasing hormone (GHRH) (10(-7) M)- or GH-releasing peptide-2 (GHRP-2)(10(-7) M)
      stimulated GH secretion. Following treatment of cells for 1-3 d with leptin, GHRH
      stimulated GH secretion was reduced and GHRP-2-stimulated GH secretion increased.
      The combined effect of GHRH and GHRP-2 on GH secretion was not altered by the
      treatment of cells with leptin for 3 d. GHRH receptor mRNA levels in cultured
      somatotrophs were decreased but GHRP receptor mRNA levels were increased by 3-d
      leptin treatment. These results suggest that leptin has a long-term effect on
      somatotrophs to reduce GHRH receptor synthesis leading to a decrease in GHRH
      stimulated GH secretion. Leptin appears, however, to have an opposite effect on
      GHRP receptor synthesis leading to an increase in GHRP-stimulated GH secretion.

PMID- 11322505
TI  - Growth hormone/insulin-like growth factor-1 response to acute and chronic growth
      hormone-releasing peptide-2, growth hormone-releasing hormone 1-44NH2 and in
      combination in older men and women with decreased growth hormone secretion.
AB  - To better appreciate the interactions of GHRP-2 and GHRH 1-44NH2 on the release
      of GH in normal adult men and women with decreased GH secretion and low serum IGF
      1 levels, a series of acute and chronic studies have been performed (n = 5 men, 5
      women). The acute iv bolus GH responses of these subjects to the two peptides
      alone and together suggest that the decreased GH secretion may be primarily due
      to a deficiency of the natural endogenous GHRP, ghrelin, rather than a decreased
      secretion of endogenous GHRH or excess secretion of SRIF. To determine whether
      the low GH response to GHRH was due to a limited capacity of pituitary to release
      GH, higher dosages of GHRP-2 alone were administered. At a dose of 1 microg/kg
      GHRP-2 the GH response was essentially the same as that elicited by 1 microg/kg
      GHRH + 0.1 microg/kg GHRP-2 while the GH response to 10 microg/kg GHRP-2 sc was
      about twice as high in both men and women. Although these subjects have a limited
      pituitary capacity to release GH, which is also an indication of decreased GH
      secretion in the presence of low serum IGF-1 levels, this alone would not explain
      the low GH response to GHRH. Furthermore, the finding that a low dose of 0.1
      microg/kg GHRP-2 augments the GH response to 1 microg/kg GHRH is strongly against
      an excess secretion of SRIF. Twenty-four hour profiles of GH secretion during
      placebo, GHRP-2, and various doses of GHRH alone and together with GHRP-2 were
      studied. In addition, 1 microg/kg/h GHRP-2 was infused continuously sc to these
      subjects for 30 d. The normal pulsatile secretion of GH as well as the serum IGF
      1 level was increased after 24 h and remained elevated for 30 d. With a
      deficiency of endogenous GHRH, the GH response of GHRP-2 would be little to none,
      while in subjects with a deficiency of the natural GHRP, the GH response to GHRH
      would be more attenuated. Thus, in chronic deficiency the GH response would be
      expected to depend on the degree of the capacity of the pituitary to release GH
      as well as the type(s) of hormonal deficiency.

PMID- 11322501
TI  - Interactive regulation of postmenopausal growth hormone insulin-like growth
      factor axis by estrogen and growth hormone-releasing peptide-2.
AB  - Estrogen is the proximate sex steroid sustaining GH secretion throughout the
      human life span in both sexes. However, very little is known about the specific
      neuroendocrine mechanisms by which estrogen activates and maintains GH secretion
      in the young or aging human. The identification of somatostatin in 1973 as a key
      negative peptidyl regulator of the GH axis and the discovery of GH-releasing
      hormone (GHRH) in 1982 as a dominant feedforward agonist of GH secretion provided
      an initial basic science foundation for exploring sex-steroid control of the GH
      IGF-1 axis. Although GH-releasing peptides (GHRPs) were first recognized in 1977
      1981, subsequent cloning of hypothalamopituitary receptors transducing potent
      secretagogue actions of GHRPs in 1996 and of an endogenous ligand for this
      effector pathway in 1999 now extend the framework for examining the mechanisms of
      estrogen-driven GH secretion in aging. Herein, we review several novel and
      multifaceted interactions in postmenopausal women between estrogen and GHRP-2. We
      combine these observations into a simplified construct of GH-axis neuroregulation
      comprising the somatostatin, GHRH, and GHRP effector pathways, as well as GH and
      IGF-1 autofeedback. We suggest the thesis that estrogen controls the interfaces
      among these pivotal regulatory peptides in hyposomatotropic postmenopausal
      individuals.

PMID- 11322506
TI  - Biologic activities of growth hormone secretagogues in humans.
AB  - Growth hormone secretagogues (GHSs) are synthetic peptidyl and nonpeptidyl
      molecules with strong, dose-dependent, and reproducible growth hormone (GH)
      releasing activity even after oral administration. GHSs release GH via actions on
      specific receptors (GHS-R) at the pituitary and, mainly, at the hypothalamic
      levels. GHSs likely act as functional somatostatin antagonists and meantime
      enhance the activity of GH-releasing hormone (GHRH)-secreting neurons. The GH
      releasing effect of GHSs is independent of gender but undergoes marked age
      related variations. Estrogens play a major role in enhancing the GH response to
      GHSs at puberty, which GHRH hypoactivity, somatostatinergic hyperactivity and
      impaired activity of the putative GHS-like ligand and receptors probably explain
      the reduced GH-releasing effect of GHSs in aging. The activity of GHSs is not
      fully specific for GH. Their slight prolactin-releasing activity probably comes
      from direct pituitary action. In physiological conditions, the ACTH-releasing
      activity of GHSs is dependent on central actions; a direct action on GHS-R in
      pituitary ACTH-secreting tumors likely explains the peculiar ACTH and cortisol
      hyperresponsiveness to GHSs in Cushing disease. GHSs have specific receptor
      subtypes in other central and peripheral endocrine and nonendocrine tissues
      mediating GH-independent biologic activities. GHSs influence sleep pattern,
      stimulate food intake, and have cardiovascular activities. GHs have specific
      binding in normal and neoplastic follicular derived human thyroid tissue and
      inhibit the proliferation of follicular-derived neoplastic cell lines. The
      discovery of ghrelin, a 28 amino acid peptide synthesized in the stomach but also
      in other tissues, has opened new fascinating perspectives of research in this
      field.

PMID- 11322507
TI  - Growth hormone secretagogue receptor family members and ligands.
AB  - We have previously reported the cloning and characterization of a new orphan G
      protein-coupled receptor (GPC-R), the growth hormone secretagogue receptor (GHS
      R), and shown that this receptor mediates the activity of the growth hormone
      releasing peptides (GHRPs) and nonpeptide ligands such as L-692,429 and MK-0677.
      Because the GHS-R obviously does not belong to any of the known GPC-R
      subfamilies, we searched for GHS-R family members by screening a human genomic
      library using low-stringency hybridization and screening a Pufferfish genomic
      library. The Pufferfish was selected because of its compact genome. From the
      human genomic library, a homolog, GPR38, with 52% identity to the GHS-R was
      isolated. From the Pufferfish library, three family members were isolated. The
      Pufferfish gene having 58% identity to the GHS-R, on expression in HEK293 cells,
      was activated with GHRP-6 and MK-0677. These results indicate that the GHS-R has
      been conserved for at least 400 million years and that the Pufferfish genome is
      appropriate for isolation of GHS-R family members. In our search for endogenous
      ligands for the orphan receptors GHS-R and GPR38, we showed that adenosine is a
      partial agonist of the GHS-R and that motilin is the endogenous ligand for GPR38.
      We also confirmed that the endogenous ligand ghrelin is a full agonist of the GHS
      R.

PMID- 11322509
TI  - Regulation of dorso/ventral patterning in the Drosophila embryo by multiple
      dorsal-interacting proteins.
AB  - The Rel family transcription factor, Dorsal, determines cell fate as a function
      of position along the dorsoventral axis of the Drosophila embryo. This process
      depends on interactions between Dorsal and a large number of additional proteins
      present in the early embryo. Cytoplasmic interactions regulate the nuclear uptake
      of Dorsal, resulting in the establishment of the Dorsal nuclear concentration
      gradient, which determines the dorsoventral polarity of the embryo. Nuclear
      protein-protein interactions then enable Dorsal to activate some target genes and
      to repress others, thereby promoting the division of the embryo into distinct
      developmental domains. Because of this broad array of regulatory interactions,
      Dorsal serves as an excellent paradigm for eukaryotic transcriptional regulation.

PMID- 11322508
TI  - Growth hormone secretagogues as diagnostic tools in disease states.
AB  - One of the most active topics in the growth hormone-IGF-1 field is that of the so
      called growth hormone secretagogues (GHS). At a time when the isolation of GHRH
      had not occurred, the GHS were developed as artificial tools to release GH. The
      interest in these groups of compounds was rekindled when it was realized that
      they were not surrogates of GHRH nor were they acting through the modulation of
      the release of either GHRH or somatostatin. With the subsequent cloning of the
      specific receptor of GHS, and today of the natural ligand for that receptor,
      named ghrelin, it soon become clear that GHS and the GHS-receptor were part of a
      new physiological system involved in GH regulation. The dual control of GH
      secretion became a trinity. GHS releases GH when administered by any route--oral,
      iv, sc, and even transdermally-with a surprising potency and reproductivity. In
      addition, GHS when administered together with GHRH exert a synergistic action on
      GH secretion and that combined administration is the most potent GH releaser to
      date. Clinical studies have demonstrated that the GHS-GHRH administration may be
      considered the new "gold standard" test of GH reserve in humans, as the GH
      secretion so elicited is not altered by gender, adiposity, or age. The combined
      administration of GHRH plus GHS is able to discriminate between healthy subjects
      and patients with adult GH deficiency, suggesting a considerable utility in the
      clinical setting.

PMID- 11322510
TI  - Influence of topoisomerase II inhibitors and ionizing radiation on growth arrest
      and cell death pathways in the breast tumor cell.
AB  - Promotion of apoptosis (which is frequently dependent on functional p53) is
      thought to be critical for the effectiveness of chemotherapy or radiotherapy.
      Studies in this as well as other laboratories have demonstrated that breast tumor
      cells are relatively refractory to apoptosis in response to modalities that
      induce DNA damage. This report describes our efforts to understand the basis for
      the absence of an apoptotic response to adriamycin and ionizing radiation in the
      breast tumor cell based on alterations in cell-cycle and apoptotic regulatory
      proteins. We also report on the permissive effects of Vitamin D3 and the Vitamin
      D3 analog EB 1089 in the promotion of apoptosis in p53-wild-type cells. Our
      studies suggest that regulation of apoptosis in the breast tumor cell may require
      modulation of signaling events other than or in addition to the p53-dependent DNA
      damage response.

PMID- 11322511
TI  - The galvanotaxis response mechanism of keratinocytes can be modeled as a
      proportional controller.
AB  - Human keratinocytes actively crawl in vitro when plated onto a collagen-coated
      glass substrate, and their direction of migration is totally random. In response
      to an imposed DC electric field, they migrate asymmetrically, moving mostly
      toward the negative pole of the field. The authors have analyzed experimental
      data reported by others to determine the basic characteristics of the cellular
      response machinery in these keratinocytes. This movement can be completely
      described mathematically using two independent variables: the speed, V, and the
      angle of migration, phi. The authors propose a model in which a steerer
      (controller without feedback) is responsible for determining the speed, and an
      automatic controller (controller with feedback) is responsible for determining
      the angle of migration. The torque to rotate is induced by a deterministic
      cellular signal and a stochastic cellular signal. The cellular machine
      characteristics are determined as follows: The angular dependence of the
      detection unit is sin phi; the detection unit detects the guiding field in a
      linear fashion; the cellular reaction unit can be described by a constant; the
      chemical amplifier, as well as the cellular motor work, is linear; the cellular
      characteristic time, which quantifies the cellular stochastic signal, is 50 min.

PMID- 11322512
TI  - Formation of a powerful capping motif corresponding to start of "helix 12" in
      agonist-bound estrogen receptor-alpha contributes to increased constitutive
      activity of the protein.
AB  - The human estrogen receptor alpha (hERalpha), a ligand-activated transcription
      factor, provides an excellent system for study of the conversion of a protein
      from inactive to active states. It binds to many different ligands which leads
      which to the expression or the suppression of genes in a cell-specific and
      promoter-specific manner, and a multitude of mutations have been identified that
      modify the activity of the receptor. Helix 12 is a key alpha-helix in the hormone
      binding domain of the hERalpha that is directly involved in transcription
      activation. In this report, tyrosine 537 has been identified as the Ncap residue
      of helix 12 in the structures of the agonist-bound hERalpha ligand-binding
      domain. A capping motif has been identified in the sequence of the hERalpha that
      corresponds to the start of helix 12 in the fully active, agonist-bound
      conformation of the receptor. Analysis of the literature indicates that, with one
      exception, substitution of amino acids at position 537, which occur more
      frequently at the Ncap than tyrosine, is correlated with increased constitutive
      activity of the hERalpha. The results are consistent with the hypothesis that
      formation of a powerful capping motif that corresponds to the start of helix 12
      in the agonist-bound receptor contributes to activation of the hERalpha. This is
      the first proposed example in which mutations that alter helix capping would lead
      to the constitutive activation of a protein. This hypothesis could therefore
      provide a novel mechanism through which mutations play a role in pathological
      processes.

PMID- 11322513
TI  - G protein-coupled, extracellular Ca2+ (Ca2+(o))-sensing receptor enables Ca2+(o)
      to function as a versatile extracellular first messenger.
AB  - The cloning of a G protein-coupled, extracellular Ca2+ (Ca2+(o))-sensing receptor
      (CaR) has afforded a molecular basis for a number of the known effects of Ca2+(o)
      on tissues involved in maintaining systemic calcium homeostasis, especially
      parathyroid gland and kidney. In addition to providing molecular tools for
      showing that CaR messenger RNA and protein are present within these tissues, the
      cloned CaR has permitted documentation that several human diseases are the result
      of inactivating or activating mutations of this receptor as well as generation of
      mice that have targeted disruption of the CaR gene. Characteristic changes in the
      functions of parathyroid and kidney in these patients as well as in the CaR
      "knockout" mice have elucidated considerably the CaR's physiological roles in
      mineral ion homeostasis. Nevertheless, a great deal remains to be learned about
      how this receptor regulates the functioning of other tissues involved in Ca2+(o)
      metabolism, such as bone and intestine. Further study of these human diseases and
      of the mouse models will doubtless be useful in gaining additional understanding
      of the CaR's roles in these latter tissues. Furthermore, we understand little of
      the CaR's functions in tissues that are not directly involved in systemic mineral
      ion metabolism, where the receptor probably serves diverse other roles. Some of
      these functions may be related to the control of intra- and local extracellular
      concentrations of Ca2+, while others may be unrelated to either systemic or local
      ionic homeostasis. In any case, the CaR and conceivably additional
      receptors/sensors for Ca2+ or other extracellular ions represent versatile
      regulators of a wide variety of cellular functions and represent important
      targets for novel classes of therapeutics.

PMID- 11322514
TI  - The Americanization of family medicine: contradictions, challenges, and change,
      1969-2000.
AB  - Family practice became the 20th medical specialty in 1969, identified by its
      leaders as a harbinger of health care reform, as well as practice excellence, and
      with expectations of continuing government support of its purpose and role. Since
      that time, the cultural and political environments have changed significantly in
      some ways, and not changed in others as initially expected, thus challenging the
      new specialty with pressures for reinvention with respect to its identity,
      function, and prestige. The most important impediment to a clear-cut role for
      family practice has been the lack of a formal administrative structure for
      primary care practice on a nationwide basis in the United States. Differentiation
      of the field from all other parts of medicine was also difficult because of the
      identification of family practice with the professional accoutrements of a
      specialty, parallel to other specialist fields. Family practice moved from an
      outsider role in medicine to a position of entrenchment in the medical
      establishment, including hospitals and academic medical centers. And, family
      practice became one of several overlapping and competing primary care fields. The
      role of family practice in US culture is now less clear than the potential role
      envisioned for it in 1969. Its multiple and not always well-defined roles in
      medicine may make it difficult to establish a clear identity for the specialty in
      the future. If it is to be successful, family practice must develop allies and
      work aggressively to establish its role in primary care. It must also work to
      institute primary care in the US medical system and act politically (as in the
      1960s), taking advantage of current cultural trends, notably the information
      revolution and the growth of biomedical research.

PMID- 11322515
TI  - A vow of connectedness: views from the road to Beaver's farm.
AB  - The doctor-patient relationship lies at the heart of family practice. Yet in a
      digital age, our understanding of this relationship has been trimmed to a
      transaction between free agents that can be fully measured and isolated in time.
      The vow of connectedness restores the broader view. We know that lasting change
      in attitude and behavior, toward healing and hope-arises from those relationships
      that encompass the doctor, his or her patients, and our common connections in the
      communities we serve.

PMID- 11322516
TI  - Family practice and social and political change.
AB  - Reform in US medicine has been a longstanding process, and it has always been
      intertwined with politics and social issues. So-called organized medicine has
      often resisted reform, but despite this resistance, many changes took place in
      the US medical system in the 1960s. The establishment of the specialty of family
      practice coincided with these changes. Although family practice was established
      with many goals in mind, many of the goals did not match the public's perceived
      needs, and there is still much unfinished business. One of family practice 's
      current tasks is to examine its accountability to the public and decide what it
      can provide for the public good.

PMID- 11322517
TI  - Is where we are where we were going? A dialogue of two generations.
AB  - This article provides the dialogue of a discussion between prominent family
      physicians from two generations. One, from the first generation of family
      physicians, was a founder of the specialty who provides insights into the origins
      of the specialty, its goals and aspirations, and possible future directions. The
      other, from a younger generation, has been a leader in managed care and its
      effects on family medicine; this physician discusses future changes in the health
      care systems and reflects on whether or not family practice will be able to adapt
      to those changes.

PMID- 11322518
TI  - What does family practice need to do next? A cross-generational view.
AB  - BACKGROUND AND OBJECTIVES: This paper presents a 60-year view of family practice,
      including its first 30 years and best projections for its next 30 years as a
      discipline and field of practice. METHODS: An objective cross-generational
      approach was taken based on available evidence. RESULTS: Five lessons are drawn
      from the past 30 years: (1) Neither medical education, medical practice, nor the
      health care system have been reformed by family medicine. (2) Family practice
      remains but one of several options for primary care. (3) The generalist
      specialist ratio has shifted farther to specialists since 1970. (4) The United
      States is unique among Western industrialized nations in having multiple
      generalist specialties. (5) The three primary care specialties are on parallel
      but separate courses. The health care system is now very different from that of
      1970, as a result of managed care; increased burden of chronic illness in an
      aging population; de-emphasis of hospital care; proliferation of primary care
      providers; increased emphasis on shared decision making with patients, cost
      effectiveness, and value of health care services; and advances in information and
      communication technology. CONCLUSIONS: The following course changes are
      recommended for family practice: (1) Embrace new paradigms of care (eg, evidence
      based medicine, population-based care, chronic disease management). (2) Modify
      practice style and redesign systems of care. (3) Embrace further differentiation
      within family practice. (4) Reassess and revise educational programs at all
      levels. (5) Increase emphasis on practice-based research and expansion of
      clinical electronic databases. (6) Explore feasibility of a unified generalist
      discipline through new alliances with other primary care specialties. (7) Build
      organizational and political strength through alliances in advocating for
      structural change of the health care system to include universal coverage and a
      generalist primary care physician for all Americans.

PMID- 11322519
TI  - What opportunities have we missed, and what bad deals have we made?
AB  - In addition to its many accomplishments, family medicine has inevitably made some
      choices that have not worked out as well. Respectful consideration of where we
      may have done so can help inform future decision making. This paper suggests some
      decisions that in retrospect appear to be bad deals, good deals gone bad, or
      missed opportunities. Bad deals include the limiting effects of our specialty's
      name and of our go-it-alone philosophy. Good deals gone bad include our affinity
      for a permanent counterculture role, our persistent belief that big is better,
      and limited evolution of our residency family practice centers. We have missed
      opportunities to lead development of a new model of patient-responsive health
      care, to change the system of payment for care, to maximize the strength of our
      discipline by links between university and community family physicians, and to
      build a powerful program of family medicine research.

PMID- 11322520
TI  - The domain of family practice: scope, role, and function.
AB  - The family physician is the physician generalist who takes professional
      responsibility for the comprehensive care of unselected patients with
      undifferentiated problems and who is committed to the person regardless of age,
      gender, illness, or organ system. The clinical specialty of family practice is
      patient centered, evidence based,family focused, and problem oriented. Family
      physicians acquire and maintain a broad array of competencies that depend on the
      needs of the patients and communities they serve. The scope of their practice is
      not defined by diagnoses or procedures but by human needs. Family physicians do
      not treat diseases; they take care of people. Nodal points in the family life
      cycle, such as birth, serious illness, and the end of life, deserve special
      attention. Family physicians are expert at managing common complaints,
      recognizing important diseases, uncovering hidden conditions, and managing most
      acute and chronic illnesses. They emphasize health promotion and disease
      prevention. Their knowledge, skills, and attitudes target community practice,
      current science, and continuous quality improvement. Family practice has a
      distinct clinical approach that requires special skills to identify concerns,
      focus issues, negotiate plans, and help solve problems. The recognition,
      integration, and prioritization of multiple concerns and the synthesis of
      solutions are critical clinical competencies. The variety of human needs require
      targeting the clinical process, sharing responsibility, and managing uncertainty.
      Focus on the person requires refined abilities to observe, communicate,
      understand, and care. Commitment to patients and populations involves activism
      and advocacy. Family medicine can lead in redefining what it means to be a
      professional, a physician, and a generalist.

PMID- 11322521
TI  - How does a changing country change family practice?
AB  - The US population is changing. Ethnic minorities are now the fastest growing
      segment of the US population, and they have higher mortality rates than the
      remainder of Americans. Members of minority groups also earn less and are twice
      as likely as other residents to lack medical insurance. Minority communities have
      poorer health and access to care than the remainder of the population. Women
      constitute more than half the total population of the United States and are half
      of the labor force. Family structure has changed such that 53% of African
      American, 32% of Hispanic, and 27% of all families were headed by a single parent
      in 1992. The elderly population has also increased and has a greater prevalence
      of chronic disease. The physician workforce has more female and younger
      physicians than in the past but a still-inadequate number of minority physicians.
      In contrast to the low proportion of minorities in the US physician workforce,
      women now comprise approximately half of medical students. A major economic trend
      affecting health care access in the United States is the lack of secure insurance
      coverage for 44 million people in 1998. Rates of no insurance are higher among
      minorities, households with no full-time worker, the near poor, and among persons
      with less education. Private charitable services, as well as the formal safety
      net systems, are experiencing financial pressure in the United States, further
      jeopardizing access to care for the uninsured. The average family in the United
      States is now working harder--but earning less money. The changing population
      mix, shifting gender balance, increasing proportion of elderly, and major
      socioeconomic trends and income disparities occurring in the United States today
      have shaped a practice environment that differs from whatfacedfamily physicians
      30 years ago. Thus, a change in approach to training and practice is needed,
      while preserving the critical relationship we have with our patients and
      continuing to meet their needs.

PMID- 11322522
TI  - Developing the knowledge base of family practice.
AB  - Borrowed and adapted knowledge is insufficient to optimize the potential of a
      comprehensive, integrative, relationship-centered generalist approach to improve
      the health of individuals, families, and communities. The knowledge base for
      family practice must be expanded by integrating multiple ways of knowing. This
      involves (1) self-reflective practice by clinicians, (2) involving the patient
      voice in generating research questions and interpreting data, (3) inquiry into
      the systems affecting health care, and (4) investigation of disease phenomena and
      treatment effects in patients over time. A multimethod, transdisciplinary,
      participatory approach is needed to create knowledge that retains connections
      with its meaning and context and therefore is readily translated into practice.
      This research integrates quantitative and qualitative traditions and involves the
      active participation of both clinicians and patients. The generation of relevant
      knowledge should be supported through (a) developing a culture of reflective
      practice among clinicians, (b) expanding the infrastructure for practice-based
      research, (c) developing a multimethod, transdisciplinary, participatory research
      paradigm, (d) longitudinal study of the process and outcomes of broad,
      integrative, relationship-centered care, and (e) incorporating pursuit of new
      knowledge as a central feature of training programs and policy. The time has come
      for the generalist disciplines to commit to the generation of new knowledge based
      on the needs of patients, families, and communities for relationship-centered,
      integrated, prioritized health care. Development of a culture of learning and
      inquiry, and the necessary research methods and skills will require a long-term
      commitment, creation of partnerships, and a focus on core principles by
      individuals and organizations.

PMID- 11322523
TI  - How will family physicians care for the patient in the context of family and
      community?
AB  - Difficulties caring for patients in the context of family and community stem from
      problems of power and vulnerability. Patients are disempowered in relation to
      physicians and to the medical care system. Physicians are disempowered in their
      ability to provide comprehensive relationship-centered care to individuals and
      families because of economic constraints on medical care and limits on continuity
      of care. Individual patients are also vulnerable to abuses of power within their
      families because of physical and sexual abuse; the recognition of such abuses and
      appropriate interventions for them requires awareness of the gender ideology that
      underlies interpersonal abuses of power. Families and communities can be
      disempowered because of vulnerabilities related to race, ethnicity, poverty, and
      homelessness. The additive effects of these vulnerabilities have created health
      disparities that are a hallmark of inequities in our country's medical system.
      Opportunities to teach students to recognize and address these disparities abound
      within medical education. Participatory training and educational action projects
      can prepare learners to lead us toward a more just and egalitarian medical system
      with the potential to change the context of family and community in which we care
      for patients. However, systematic commitment from educational programs is
      necessary to produce activated clinicians, teachers, and researchers to achieve
      these changes.

PMID- 11322524
TI  - What can technology do to, and for, family medicine?
AB  - Medical technology can be divided into information technology, diagnostic
      technology, and therapeutic technology. These technologies can enhance the care
      of patients in a family practice; they also have the potential to diminish or
      fragment family practice when the technologies can only be provided by
      specialists. While some family physicians have an aversion to technological
      advances, we believe it is imperative that family physicians participate in the
      development of technologies that enhance family practice and improve patient
      outcomes in primary care practice. These include electronic medical records,
      decision support systems, tools for managing medical information, and others.
      Criteria are presented to help determine when these new technologies should be
      adopted into practice.

PMID- 11322525
TI  - The view from 2020: how family practice failed.

PMID- 11322526
TI  - Family practice triumphs by the year 2020: what will we have done right?
AB  - For family practice in the United States to be considered a success in the year
      2020, several things will need to be done right between now and then. These
      include (1) an emphasis on quality of care, (2) a dependence on new technologies
      to enhance quality, (3) availability of and access to primary care for the entire
      US population, (4) increased political power for the specialty of family
      practice, (5) enhanced research and research funding, and (6) learning to work
      with patients so that they are the masters of their own care. If successful in
      2020, family physicians will be perceived as quality physicians who use
      technology that everyone wants and who use their political power to advocate for
      patients' rights to quality health care and the research important to the
      discipline and quality health care. Family physicians will have become the "go-to
      doctors" who put patients in charge.

PMID- 11322527
TI  - Classification of electrocardiographic P-wave morphology.
AB  - The atrial activity of the human heart is normally visible in the
      electrocardiogram as a P-wave. In patients with intermittent atrial fibrillation,
      a different P-wave morphology can sometimes be seen, indicating atrial conduction
      defects. The purpose of this study was to develop a method to discriminate
      between such P-waves and normal ones. 20 recordings of each type were used in a
      classification which, based on impulse response analysis of the P-wave and linear
      discrimination between various parameters, produced a correct classification in
      37 of the 40 recordings (sensitivity 95%, specificity 90%).

PMID- 11322528
TI  - A nonlinear approach to modeling of electrically stimulated skeletal muscle.
AB  - This paper is concerned with the development and analysis of a nonlinear approach
      to modeling of the contraction of electrically stimulated skeletal muscle. The
      model structure is based on a network of locally valid linear models which are
      blended together by a scheduler. Data are from experiments with rabbit tibialis
      anterior muscles in which the muscles contracted isometrically while being
      stimulated by supramaximal impulses with randomly varying inter-pulse intervals.
      The model accounts for nonlinear effects due to variations of the stimulation
      frequency, such as the "catch-like" effect. It is shown that this modeling
      technique is suitable for modeling the contraction of muscles with very different
      characteristics, such as muscle with a majority of fast motor units and muscle
      with mainly slow motor units. The approach is also suitable as a basis for the
      design of muscle stimulation controllers. Index Terms-Functional electrical
      stimulation, local model network, muscle modeling, nonlinear system
      identification.

PMID- 11322529
TI  - The effects of interpulse interval on stochastic properties of electrical
      stimulation: models and measurements.
AB  - It is known that some cochlear implant users have improved speech perception
      using higher rates of interleaved pulsatile stimulation. There are, however,
      significant limitations on their performance presumably due in part to temporal
      and spatial interactions. To address these limitations, we have examined
      refractory characteristics of the auditory nerve using experimental animal models
      and computational simulations. A stochastic model of the node of Ranvier modified
      for mammalian sodium channel kinetics has been developed to calculate the masked
      input-output (I/O) functions for different interpulse intervals (IPI) [26]. The
      model is based upon 1000 voltage-gated sodium channels and incorporates
      parameters such as nodal resistance and capacitance. The relative spread (RS)
      [35] calculated from the I/O functions was typically 0.03 for 17 different IPIs
      between 450 micros and 6 ms for cathodal stimuli. For IPI = 830 and 870 micros,
      the RS was ten times greater than those for other IPIs. Although it is not fully
      understood how the electrically evoked compound action potential (EAP) data are
      related to single fiber data, the RS of single fibers is a partial contributor
      [19]. We have measured the EAP using a monopolar intracochlear stimulating
      electrode and a recording electrode placed directly on the nerve and have
      observed changes in slope of EAP growth functions consistent with the theoretical
      RS values. These results have significant implications for speech coding in a
      cochlear implant since they suggest an increased membrane noise for pulse trains
      of specific rates.

PMID- 11322530
TI  - Flow effect on lesion formation in RF cardiac catheter ablation.
AB  - This study investigated the flow effect on the lesion formation during radio
      frequency cardiac catheter ablation in temperature-controlled mode. The blood
      flow in heart chambers carries heat away from the endocardium by convection. This
      cooling effect requires more power from the ablation generator and causes a
      larger lesion. We set up a flow system to simulate the flow inside the heart
      chamber. We performed in vitro ablation on bovine myocardium with three different
      flow rates (0 L/min, 1 L/min and 3 L/min) and two target temperatures (60 degrees
      C and 80 degrees C). During ablation, we also recorded the temperatures inside
      the myocardium with a three-thermocouple temperature probe. The results show that
      lesion dimensions (maximum depth, maximum width and lesion volume) are larger in
      high flow rates (p<0.01). Also, the temperature recordings show that the tissue
      temperature rises faster and reaches a higher temperature under higher flow rate.

PMID- 11322531
TI  - Toroidal coil models for transcutaneous magnetic stimulation of nerves.
AB  - A novel design of coils for transcutaneous magnetic stimulation of nerves is
      presented. These coils consist of a toroidal winding around a high-permeability
      material (Supermendur) core embedded in a conducting medium. Theoretical
      numerical calculations are used to analyze the effect of the design parameters of
      these coils, such as coil width, toroidal radius, conducting layer thickness and
      core transversal shape on the induced electric fields in terms of the electric
      field strength and distribution. Results indicate that stimulation of nerves with
      these coils has some of the advantages of both electrical and magnetic
      stimulation. These coils can produce localized and efficient stimulation of
      nerves with induced electric fields parallel and perpendicular to the skin
      similar to surface electrical stimulation. However, they retain some of the
      advantages of magnetic stimulation such as no risk of tissue damage due to
      electrochemical reactions at the electrode interface and less uncomfortable
      sensations or pain. The driving current is reduced by over three orders of
      magnitude compared to traditional magnetic stimulation, eliminating the problem
      of coil heating and allowing for long duration and high-frequency magnetic
      stimulation with inexpensive stimulators.

PMID- 11322532
TI  - Investigation of 3-D mechanical properties of blood vessels using a new in vitro
      tests system: results on sheep common carotid arteries.
AB  - In order to investigate the three-dimensional (3-D) mechanical properties of
      blood vessels, a new experimental device is described allowing in vitro static
      and dynamic measurements on segments of arteries with high technical
      performances. Static tests are applied to sheep common carotid arteries.
      Considering a thick-walled cylindrical model of orthotropic material under large
      deformations, a classical 3-D approach based on strain energy density is used to
      calculate the resulting mechanical behavior law in radial and circumferencial
      directions and stresses distribution throughout the wall thickness. Results are
      presented with reference to unloaded and zero-stress initial state thanks to
      simple measurements of inner and outer circumferences. A particular ratio
      relating the two main stresses (circumferential and longitudinal) is calculated
      that put into the forth the progressive modifications in the direction of the
      predominant stress in the wall and the specific radial location where these
      changes occur. We observe that this point location is a function of the test
      conditions of the specimen, i.e., stretching length and level of pressure.

PMID- 11322533
TI  - A new method for pulse oximetry possessing inherent insensitivity to artifact.
AB  - A new method for pulse oximetry is presented that possesses an inherent
      insensitivity to corruption by motion artifact, a primary limitation in the
      practical accuracy and clinical applicability of current technology. Artifact
      corruption of the underlying photoplethysmographic signals is reduced in real
      time, using an electronic processing methodology that is based upon inversion of
      a physical artifact model. This fundamental approach has the potential to provide
      uninterrupted output and superior accuracy under conditions of sustained subject
      motion, therefore, widening the clinical scope of this useful measurement. A new
      calibration technique for oxygen saturation is developed for use with these
      processed signals, which is shown to be a generalization of the classical
      interpretation. The detailed theoretical and practical issues of implementation
      are then explored, highlighting important engineering simplifications implicit in
      this new approach. A quantitative investigation of the degree of insensitivity to
      artifact is also undertaken, with the aid of a custom electronic system and
      commercial pulse oximeter probes, which is compared and contrasted with the
      performance of a conventional implementation. It is demonstrated that this new
      methodology results in a reduced sensitivity to common classes of motion
      artifact, while retaining the generality to be combined with conventional signal
      processing techniques.

PMID- 11322534
TI  - Three-dimensional tumor perfusion reconstruction using fractal interpolation
      functions.
AB  - It has been shown that the perfusion of blood in tumor tissue can be approximated
      using the relative perfusion index determined from dynamic contrast-enhanced
      magnetic resonance imaging (DE-MRI) of the tumor blood pool. Also, it was
      concluded in a previous report that the blood perfusion in a two-dimensional (2
      D) tumor vessel network has a fractal structure and that the evolution of the
      perfusion front can be characterized using invasion percolation. In this paper,
      the three-dimensional (3-D) tumor perfusion is reconstructed from the 2-D slices
      using the method of fractal interpolation functions (FIF), i.e., the piecewise
      self-affine fractal interpolation model (PSAFIM) and the piecewise hidden
      variable fractal interpolation model (PHVFIM). The fractal models are compared to
      classical interpolation techniques (linear, spline, polynomial) by means of
      determining the 2-D fractal dimension of the reconstructed slices. Using FIFs
      instead of classical interpolation techniques better conserves the fractal-like
      structure of the perfusion data. Among the two FIF methods, PHVFIM conserves the
      3-D fractality better due to the cross correlation that exists between the data
      in the 2-D slices and the data along the reconstructed direction. The 3-D
      structures resulting from PHVFIM have a fractal dimension within 3%-5% of the one
      reported in literature for 3-D percolation. It is, thus, concluded that the
      reconstructed 3-D perfusion has a percolation-like scaling. As the perfusion term
      from bio-heat equation is possibly better described by reconstruction via fractal
      interpolation, a more suitable computation of the temperature field induced
      during hyperthermia treatments is expected.

PMID- 11322535
TI  - Role of blood shear stress in the regulation of vascular smooth muscle cell
      migration.
AB  - Smooth muscle cell (SMC) migration from the media to the intima of blood vessels
      contributes to neointimal formation and atherogenesis. Here, we demonstrate how
      blood shear stress regulates vascular SMC migration in the encapsulating tissue
      of a micro-cylinder implanted in the center of the rat vena cava with the micro
      cylinder perpendicular to blood flow. In this model, the micro-cylinder was
      exposed to a laminar flow with a known shear stress field in the leading region
      and a vortex flow in the trailing region. After surgery, the micro-cylinder was
      encapsulated by a thrombus-like tissue within one day, followed by SMC migration
      from the vena cava to the encapsulating tissue from day 3 to 20. SMC migration
      was time-dependent with a peak migration speed at day 5. At each given time
      (excluding day 1), blood shear stress exerts an inhibitory effect on SMC
      migration with significantly suppressed SMC migration in the laminar flow region
      than in the stagnation, separation, and vortex flow regions. SMCs were relatively
      parallel to the shear stress direction in high shear stress regions, whereas
      perpendicular to the shear stress direction in low shear stress regions. These
      results suggest that blood shear stress plays a role in regulating SMC migration
      and orientation in this model.

PMID- 11322536
TI  - Detection and quantification of intraperitoneal fluid using electrical impedance
      tomography.
AB  - A prototype electrical impedance tomography system was evaluated prior to its use
      for the detection of intraperitoneal bleeding, with the assistance of patients
      undergoing continuous ambulatory peritoneal dialysis (CAPD). The system was
      sensitive enough to detect small amounts of dialysis fluid appearing in
      subtractive images over short time periods. Uniform sensitivity to blood
      appearing anywhere within the abdominal cavity was produced using a post
      reconstructive filter that corrected for changes in apparent resistivity of
      anomalies with their radial position. The image parameter used as an indication
      of fluid quantity, the resistivity index, varied approximately linearly with the
      quantity of fluid added. A test of the system's response to the introduction of
      conductive fluid out of the electrode plane (when a blood-equivalent fluid was
      added to the stomach) found that the sensitivity of the system was about half
      that observed in the electrode plane. Breathing artifacts were found to upset
      quantitative monitoring of intraperitoneal bleeding, but only on time scales
      short compared with the fluid administration rate. Longer term breathing changes,
      such as those due to variations in the functional residual capacity of the lungs,
      should ultimately limit the sensitivity over long time periods.

PMID- 11322537
TI  - Determining the temperature distribution of a model vessel wall under pulsed
      laser irradiation: an experimental attempt to measure fibrous cap thickness and
      detect temperature elevation in atherosclerotic lesions.
AB  - In order to measure the temperature of atherosclerotic plaques, we developed a
      method to determine the temperature distribution of vessel walls using a three
      layer phantom agar model. Under pulsed-laser irradiation, the thickness of upper
      layer corresponding to fibrous cap overlying the middle layer corresponding to
      atherosclerotic lesion could be calculated. The temperature was calculated from
      measured temperature changes under pulsed-laser irradiation.

PMID- 11322538
TI  - A low-cost transmittance transducer for measurement of blood oxygen saturation in
      extracorporeal circuits.
AB  - Designs for a low-cost dual wavelength transducer based on light transmittance
      and a disposable cuvette for monitoring oxygen saturation (SO2) in extracorporeal
      arterial and venous blood are presented. The transducer utilizes red and infrared
      light-emitting diodes and a large photodiode; it is designed to attach to a flow
      through cuvette modified from 3/8-in x3/8-in bypass-circuit connectors. A mock
      extracorporeal circulation system was assembled to evaluate operation of the
      transducer at a controlled blood SO2 and the relationship between light
      transmittance and hemodilution. SO2 was calculated based on multiple linear
      regression analyses. The results show a high correlation between the SO2 obtained
      with the equipment designed and values measured with commercial gasometric
      equipment in the range of 50% to 100% (r2 = 0.976, error <2%). The method
      presented allows continuous and real time measurement of whole blood SO2 with a
      low-cost transmittance transducer.

PMID- 11322539
TI  - Comment on "limit cycle oscillations in pacemaker cells".

PMID- 11322540
TI  - The persistent radical effect in organic synthesis.
AB  - The persistent radical effect (PRE) is a principle that explains the highly
      selective cross-coupling between a persistent and a transient radical when both
      species are formed at equal rates. In this paper, the concept of the PRE is
      briefly discussed. Applications of the PRE in different reactions such as Co
      mediated radical addition and cyclization reactions, Kharasch reactions catalyzed
      by transition metals, the Barton reaction, and our nitroxide-mediated tin-free
      radical cyclizations are presented. Some future perspectives for the PRE in
      organic synthesis are also provided.

PMID- 11322541
TI  - On ring carbomers of cyclobutane, cyclopentane, and cyclodecane and cyclization
      reactions through bis(alkynyl-propargyl) coupling.
AB  - A copper-mediated procedure for terminal alkynyl-propargyl coupling has been
      applied to "skipped" bis-terminal undecatetrayne and 1,4-bis(pseudo)halobut-2
      ynes with the aim of preparing ring carbomers of representative strained and
      loose cycloalkanes, namely [N]pericyclynes. Two unprecedented, cyclic. "skipped"
      polyynes with CH2 vertices have been isolated as mixtures of diastereoisomers: an
      isomer 1b and a dimer 2a of [5]pericyclyne 1a. The isomer 1b is a cyclotetrayne
      with an exocyclic allene function resulting from a unique formal SN process. Its
      structure has been established by 1H/13C HMQC and HMBC two-dimensional NMR
      analysis. According to density functional theory calculations, it is about 6
      kcalmol(-1) more stable than [5]pericyclyne (1a). Compound 1b can also be
      regarded as a C13-relaxed [4]pericyclyne, a long sought "skipped" C12 tetrayne.
      The dimer 2a is a C30 ring that results from a formal SN process. It is a stable
      ring carbomer of cyclodecane, that is, a [10]pericyclyne, with four CH2 vertices.

PMID- 11322542
TI  - Influence of highly preorganised 7,7-diphenylnorbornane in the free energy of
      edge-to-face aromatic interactions.
AB  - The influence of preorganised 7,7-diphenylnorbornane in the stability (Ka) of
      host-guest complexes as well as in the determination of the energy of edge-to
      face aromatic interactions has been investigated. The guest molecules studied
      bind more strongly with hosts that contain the cofacial 7.7-diphenylnorbornane
      subunit than with similar hosts that have a 1,1-diphenylcyclohexane subunit. On
      the other hand, the value of the edge-to-face aromatic interactions calculated
      for our complexes (-0.2 +/- 0.6 kJmol(-1)) is significantly lower (by a factor of
      seven) than the one previously reported in the literature. This result highlights
      the importance of entropic factors in the determination of weak noncovalent
      interactions.

PMID- 11322543
TI  - Structural consequences of metal complexation of cyclo[Pro-Phe-Phe-Ala-Xaa]2
      decapeptides.
AB  - The conformational features of both free and Ca2+-complexed cyclo[Pro-Phe-Phe-Ala
      Xaa]2 (with Xaa= Glu(OtBu), Lys(CIZ), Leu, and Ala) in solution have been
      determined by NMR spectroscopy and extensive distance-geometry calculations. The
      decapeptides are conformationally homogeneous in solution and show common
      structural features in their free and complexed forms. The structures of the free
      form contain only trans peptide bonds and are topologically similar to the
      structure of gramicidin-S, folded up in two antiparallel extended structures,
      stabilized by interstrand hydrogen bonds, and closed at both ends by two beta
      turns. In contrast, the Ca2+-complexed peptides present two cis peptide bonds and
      are generally similar to those observed for the metal-complexed forms of
      antamanide and related analogues, folded into a saddle shape with two beta-turns.
      The Glu(OtBu)-, Leu-, and Lys(ClZ)-containing peptides examined here maintain the
      biological activity of the cyclolinopeptide A in their ability to competitively
      inhibit cholate uptake. The natural antamanide and cyclolinopeptide A are both
      able to inhibit the uptake of bile salts into hepatocytes. They share the same
      postulated active sequence Pro-Phe-Phe. Based on our structural results, we
      conclude that the ability to adopt a global conformation, characterized by a
      clear amphipathic separation of hydrophobic and hydrophilic surfaces, is an
      important feature for the functioning of this class of peptides.

PMID- 11322544
TI  - Acid-labile protecting groups for the synthesis of lipidated peptides.
AB  - Lipidated peptides and their neolipoprotein derivatives are efficient tools for
      the investigation of biological processes in molecular detail. These compounds
      are often acid- and base-labile, and their synthesis requires the use of a
      combination of blocking groups that can be removed under very mild conditions. In
      this article we demonstrate that the Boc urethane and different trityl-type
      protecting groups can be cleaved selectively under acidic conditions that are
      mild enough to be compatible with the demands of lipopeptide synthesis. Thus, the
      Boc group was cleaved with TMS triflate in the presence of lutidine, and the
      methyltrityl (Mtt) and the methoxytrityl (Mmt) group were removed with 1% TFA in
      dichloromethane in the presence of triethylsilane as cation scavenger. Removal of
      the phenylfluorenyl group was achieved with up to 3% TFA in dichloromethane in
      the presence of triethylsilane at 0 degrees C. These protecting-group techniques
      were successfully applied in the synthesis of differently lipidated H-Ras
      peptides.

PMID- 11322546
TI  - Solid-phase synthesis of homogeneous ruthenium catalysts on silica for the
      continuous asymmetric transfer hydrogenation reaction.
AB  - The solid-phase synthesis of new asymmetric transfer hydrogenation catalysts as
      well as the use of these silica supported systems in batch and flow reactors is
      reported. The ruthenium complex of NH-benzyl-(1R,2S)-(-)-norephedrine covalently
      tethered to silica showed a high activity and enantioselectivity in the reduction
      of acetophenone. In three consecutive batchwise catalytic runs, we obtained ee
      values of 88%. In a continuous flow reactor, a very constant catalytic activity
      was observed; no catalyst deactivation occurred over a period of one week. This
      has been ascribed to successful site isolation. Using optimized conditions in
      this flow reactor, the ee was as high as 90% at 95% conversion. The supported
      catalysts generally show the same trend in catalyst performance as in solution.
      The viability of our approach was further shown in one example, the ruthenium(II)
      complex of (1S,2R)-(+)-2-amino-1,2-diphenylethanol, for which an enantiomeric
      excess of 58% was observed, which is nearly three times higher than its
      homogeneous analogue.

PMID- 11322545
TI  - Macrochelation, cyclometallation and G-quartet formation: N3- and C8-bound PdII
      complexes of adenine and guanine.
AB  - The reactions of Pd(II) ions with a series of chelate-tethered derivatives of
      adenine and guanine have been studied and reveal a difference in the reactivity
      of the purine bases. Reactions of [PdCl2(MeCN)2] and A-alkyl-enH x Cl (alkyl =
      propyl or ethyl, A adenine, en = ethylenediamine) yield the monocationic species
      [PdCl(A-N3-Et-en)]+ (1) and [PdCl(A-N3-Pr-en)]+ (2). Both involve co-ordination
      at the minor groove site N3 of the nucleobase as confirmed by single-crystal X
      ray analysis. Reactions with the analogous G-alkyl-enH x Cl derivatives
      (G=guanine, alkyl = ethyl or propyl) were more complex with a mixture of species
      being observed. For G-Et-en HCI a product was isolated which was identified as
      [PdCl(G-C8-Et-en)]+ (3). This compound contains a biomolecular metal-carbon bond
      involving C8 of the purine base. Crystallography of a product obtained from
      reaction of G-Pr-enH x Cl and [Pd(MeCN)4][NO3]2 reveals an octacationic
      tetrameric complex (4), in which each ligand acts to bridge two metal ions
      through a combination of a tridentate binding mode involving the diamine and N3
      and monodentate coordination at N7.

PMID- 11322547
TI  - Chemistry and properties of cycloheptatetraene in the inner phase of a
      hemicarcerand.
AB  - Low-temperature photolysis of phenyldiazirine, incarcerated inside a
      hemicarcerand which is built from two cavitands connected by four butane-1,4
      dioxy linker groups, yields transient phenylcarbene; this carbene then undergoes
      ring photochemical expansion to cycloheptatetraene in low yield. Competitively,
      the transiently formed phenylcarbene reacts with the surrounding hemicarcerand.
      The yield of the photochemical ring expansion was increased when the photolysis
      was carried out inside a partially deuterated hemicarcerand. Two insertion
      products resulting from an intramolecular phenylcarbene insertion into an acetal
      C-H(D) bond or an alpha-C-H bond of a butane-1,4-dioxy linker group have been
      isolated and characterized. The measured isotope effect for insertion into an
      acetal C-H(D) bond at 15.5 K is consistent with a reaction of singlet
      phenylcarbene. Incarcerated cycloheptatetraene is stable for a limited time at
      100 degrees C and almost infinitely stable at room temperature in the absence of
      oxygen. NOESY experiments provide the distance ratio r21/r23 = 1.134 +/- 0.01
      between protons H1-H2 and H2-H3 of cycloheptatetraene which is consistent with
      its twisted structure. Low-temperature photolysis of phenyldiazirine,
      incarcerated inside a chiral hemicarcerand which is built from two cavitands
      connected with three butane-1,4-dioxy and one (S,S)-2,3-O-isopropylidene-2,3
      dihydroxybutane-1,4-dioxy linker group yields two diastereomeric
      cycloheptatetraene hemicarceplexes in a 2:3 ratio (30% total yield). Variable
      temperature 1H NMR studies provided a lower limit of deltaG++ = 19.6 kcalmol(-1)
      for the enantiomerization barrier of cycloheptatetraene. Incarcerated
      cycloheptatetraene reacts rapidly with oxygen to yield benzene and carbon dioxide
      via the 1,2-dioxaspiro[2,6]nona-4,6,8-triene intermediate. Different mechanisms
      for the formation of this spirodioxirane intermediate are discussed based on the
      measured rate of the oxygen addition. The activation parameters for the
      decarboxylation of the spirodioxirane have been measured in different bulk
      solvents. The free energy of activation shows very little solvent dependency.
      However. a strong propensity for enthalpy-entropy compensation due to a solvent
      reorganization that accompanies the reaction coordinate is observed.

PMID- 11322549
TI  - Cyclic sulfonimidates by dynamic diastereomer-differentiating cyclisation: large
      scale synthesis and mechanistic studies.
AB  - A dynamic diastereomer differentiating cyclisation is the key step in a new large
      scale synthesis of both enantiomers of the cyclic sulfonimidates 1 (Aldrich no.
      54099-4) and ent-1 (Aldrich no. 54412-4). These are valuable starting materials
      in the asymmetric synthesis of chiral oxa- and azaheterocyclic compounds. NMR
      spectroscopic studies on the reacting system reveal N-chloro sulfinamides to be
      reactive intermediates in the oxidative chlorination of sulfinamides with tert
      butyl hypochlorite and allow for the inspection of the configurational behaviour
      of the involved sulfonimidoyl chlorides and sulfonimidoyl bromides.

PMID- 11322548
TI  - An allosteric synthetic catalyst: metal ions tune the activity of an artificial
      phosphodiesterase.
AB  - A trinuclear metal complex of general formula (L-H)M3(Mf)2 represents the first
      allosteric low molecular weight catalyst. L is a polyaza ligand having a
      tetradentate and two bidentate metal binding sites, Ms is a "structural"
      (allosteric) metal, and Mf are functional (catalytic) metals which interact with
      a substrate. In mononuclear [(L-H)Ms]+ complexes [(L-H)Cu(MeOH)]ClO4 (1a). [(L
      H)Cu]NO3 x 2H2O (1b), [(L-H)Ni]ClO4 x 4H2O (2), and [(L-H)Pd]ClO4 x 2H2O (3),
      prepared from L and M2+ salts, the metal is strongly bound by an in-plane N4
      coordination (confirmed by X-ray crystal structure determination of la).
      Formation of trinuclear complexes [(L-H)MsCu2]5+, with two functional Cu2+ ions
      coordinated to the bidentate sites of L, was evidenced in solution by photometric
      titration and by isolation of [(L-H)Cu3][PO4][ClO4]2 x 9H2O (4). The trinuclear
      complexes catalyze the cleavage of RNA-analogue 2-(hydroxypropyl)-p-nitrophenyl
      phosphate (HPNP), an activated phosphodiester. From a kinetic analysis of the
      cleavage rate at various HPNP concentrations, parameters KHPNP (the equilibrium
      constant for binding of HPNP to [(L-H)MsCu2]5+ and kcat (first-order rate
      constant for cleavage of HPNP when bound to the catalyst) were derived: KM= 170
      (Ms= Cu2+), 340 (Ms = Ni2+), 2,600 (Ms = Pd2+) M(-1), kcat = 17 x 10(-3) (Ms=
      Cu2+) 3.1 x 10(-3) (Ms=Ni2+), 0.22 x 10(-3) (Ms = Pd2+) s(-1). Obviously, the
      nature of the allosteric metal ion Ms strongly influences both substrate affinity
      and reactivity of the catalyst [(L-H)MsCu2]5+. Our interpretation of this
      observation is that subtle differences in the ionic radius of Ms and in its
      tendency to distort the N4-Ms coordination plane have a significant influence on
      the conformation of the catalyst (i.e., preorganization of functional Cu2+ ions)
      and thus on catalytic activity.

PMID- 11322550
TI  - [15]crown-5: an unsymmetrical bifacial hydrogen-bond acceptor in crystal
      engineering.
AB  - Reaction of [15]crown-5 with erbium nitrate and a range of nickel salts results
      in the formation of the hydrogen-bonded chain species [Er(NO3)3(H2O)3]. [15]crown
      5 H2O (3), [Ni(H2O)6]Br2 [15]crown-5 2H2O (4), [Ni(H2O)6](ClO4)2 x [15]crown-5
      2H2O (5), [Ni(H2O)6](NO3)2 [15]crown-5 2H2O (6) and [[Ni(H2O)4]2(muCl)2]Cl2
      [15]crown-5 (7). Complexes 3-5 exhibit low symmetry structures with 2-4 unique
      crown ether molecules, whereas 6 and 7 are more symmetrical. The factors
      contributing to this behaviour are discussed within the wider context of
      [15]crown-5 structures in the Cambridge Structural Database.

PMID- 11322551
TI  - A study of gas-phase reactions of radical cations of mono- and dihaloethenes with
      alcohols by FT-ICR spectrometry and molecular orbital calculations: substitution
      versus oxidation.
AB  - The ion-molecule reactions of the radical cations of vinyl chloride (1), vinyl
      bromide (2), 1,2-dichloroethene (3), 1,2-dibromoethene (4), 1,1-dichloroethene
      (5), and 1,1-dibromoethene (6) with methanol (MeOH) and ethanol (EtOH) have been
      studied by FT-ICR spectrometry. In the case of EtOH as reactant the oxidation of
      the alcohol to protonated acetaldehyde by a formal hydride transfer to the
      haloethene radical cation is the main process if not only reaction observed with
      the exception of the 1,2-dibromoethene radical cation which exhibits slow
      substitution. In secondary reactions the protonated acetaldehyde transfers the
      proton to EtOH which subsequently undergoes a well known condensation reaction of
      EtOH to form protonated diethyl ether. With MeOH as reactant, the 1,2
      dihaloethene radical cations of 3.+ and 4.+ exhibit no reaction, while the other
      haloethene radical cations undergo the analogous reaction sequence of oxidation
      yielding protonated formaldehyde. Generally, bromo derivatives of haloethene
      radical cations react predominantly by substitution and chloro derivatives by
      oxidation. This selectivity can be understood by the thermochemistry of the
      competing processes which favors substitution of Br while the effect of the
      halogen substituent on the formal hydride transfer is small. However, the
      bimolecular rate constants and reaction efficiencies of the total reactions of
      the haloethene radical cations with both alcohols exhibit distinct differences,
      which do not follow the exothermicity of the reactions. It is suggested that the
      substitution reaction as well as the oxidation by formal hydride transfer
      proceeds by mechanisms which include fast and reversible addition of the alcohol
      to the ionized double bond of the haloethene radical cation which generates a
      beta-distonic oxonium ion as the crucial intermediate. This intermediate is
      energetically excited by the exothermic addition and fragments either directly by
      elimination of a halogen substituent to complete the substitution process or
      rearranges by hydrogen migration before dissociation into the protonated aldehyde
      and a beta-haloethyl radical. Reversible addition and hydrogen migrations within
      a long lived intermediate is proven experimentally by H/D exchange accompanying
      the reaction of the radical cations of vinyl chloride (1) and 1,1-dichloroethene
      (5) with CD3OH. The suggested mechanisms are substantiated by ab initio molecular
      orbital calculations.

PMID- 11322552
TI  - Unique structural properties of the Mg-Al hydrotalcite solid base catalyst: an in
      situ study using Mg and Al K-edge XAFS during calcination and rehydration.
AB  - The changes in the layered structure of Mg-Al hydrotalcite (Mg/ Al = 2) during
      heat treatment have been investigated by using in situ XAFS simultaneously at the
      Mg and Al K-edges. The development of unique in situ instrumentation allowed the
      coordination environments at both the Mg and Al centers to be monitored as a
      function of the temperature and heat treatment. The results of this study show
      that the hydrotalcite structure is highly flexible, and should lead to the
      further development of hydrotalcites as new solid basic catalysts. Moreover, the
      Mg and Al cations in the cation layers show different behavior as a function of
      temperature. The coordination of some octahedral Al ions decreases already at a
      temperature of 425 K, whereas the coordination about Mg does not show any
      modification at this temperature. However, hydrotalcite treated at 425 K,
      followed by cooling down to room temperature resulted in a complete reversal to
      the original octahedral Al coordination. It is proposed that Al-OH bond breakage
      occurs at 425 K, without the evolution of H2O. This bond is restored after
      cooling to room temperature. The actual dehydroxylation of hydrotalcite commences
      between 425 and 475 K, as indicated by a change in coordination of both the Mg
      and Al centers. This is accompanied by the evolution of H2O molecules and the
      changes are hence irreversible without the presence of excess water. Heat
      treatment at 725 K leads to the development of an MgO-like phase (octahedral Mg)
      and a mixed octahedral/tetrahedral Al phase. A subsequent rehydration at room
      temperature entirely restores the original coordination about the Al and Mg
      centers of hydrotalcite to a distance of 15 A, to which XAFS spectroscopy is
      sensitive.

PMID- 11322553
TI  - Electron transfer through molecular bridges between reducible
      pentakis(thiophenyl)benzene subunits.
AB  - "Dimers" 3, 4 and 7, which consist of two reducible pentakis(thiophenyl)benzene
      subunits linked by different molecular structures, have been synthesised as model
      compounds for reducible molecular-wire-type synthons to represent differences in
      the electron-transfer ability as a function of the bridging structure. The
      bridging units consist of para-divinylbenzene in 3, bis-hydrazone in 4 and
      diacetylene in 7. Their ability to transfer electrons from one reducible subunit
      to the other was investigated by electrochemical and spectroelectrochemical
      methods and, in the case of 4 and 7, the solid-state structures support the
      experimental findings. The para-divinylbenzene bridge in 3 was found to
      completely isolate the reducible structures (Class I system). In contrast, the
      diacetylene bridge in 7 electronically connects the two reducible structures
      (Class III system) and, thus, demonstrates its potential application as a
      "molecular wire". The bis-hydrazone-linked compound 4 displayed only a low level
      of electronic connection between the subunits and was only observed in the
      spectroelectrochemical investigation.

PMID- 11322554
TI  - Rate and mechanism of the reversible formation of cationic (eta3-allyl)-palladium
      complexes in the oxidative addition of allylic acetate to palladium(0) complexes
      ligated by diphosphanes.
AB  - The oxidative addition of the allylic acetate, CH2=CH-CH2-OAc, to the
      palladium(o) complex [Pd0(P,P)], generated from the reaction of [Pd(dba)2, with
      one equivalent of P,P (P,P = dppb = 1,4-bis(diphenylphosphanyl)butane, and P,P =
      dppf = 1,1'-bis(diphenylphosphanyl)ferrocene), gives a cationic (eta3
      allyl)palladium(II) complex, [(eta3-C3H5)Pd(P,P)+]. with AcO as the counter
      anion. This reaction is reversible and proceeds through two successive
      equilibria. The overall equilibrium constants have been determined in DMF.
      Compared with PPh3, the overall equilibrium lies more in favor of the cationic
      (eta3-allyl)palladium(II) complex when bidentate P,P ligands are considered in
      the order: dppb > dppf > PPh3. The reaction proceeds via a neutral intermediate
      complex [(eta2-CH=CH-CHCH2-OAc)Pd0(P,P)], which has been kinetically detected.
      The rate constants of the successive steps have been determined in DMF by UV
      spectroscopy and conductivity measurements. The overall complexation step of the
      Pd0 by the allylic acetate C=C bond is faster than the oxidative
      addition/ionization step which gives the cationic (eta3-allyl)palladium(II)
      complex.

PMID- 11322555
TI  - Synthesis and molecular recognition of novel oligo(ethylenediamino) bridged
      bis(beta-cyclodextrin)s and their copper(II) complexes: enhanced molecular
      binding ability and selectivity by multiple recognition.
AB  - Four bridged bis(beta-cyclodextrin)s tethered by different lengths of
      oligo(ethylenediamine)s have been synthesized and their inclusion complexation
      behavior with selected substrates elucidated by circular dichroism spectroscopy
      and fluorescence decay. In order to study their binding ability quantitatively,
      inclusion complexation stability constants with four dye guests, that is,
      brilliant green (BG), methyl orange (MO), ammonium 8-anilino-1
      naphthalenesulfonic acid (ANS), and sodium 6-(p-toluidino)-2-naphthalenesulfonate
      (TNS), have been determined in aqueous solution at 25 degrees C with
      spectrophotometric, spectropolarimetric, or spectrofluorometric titrations. The
      results obtained indicate that the two tethered cyclodextrin units might
      cooperatively bind to a guest, and the molecular binding ability toward model
      substrates, especially linear guests such as TNS and MO, could be extended. The
      tether length plays a crucial role in the molecular recognition, the binding
      constants for ANS and TNS decrease linearly with an increase in the tether length
      of dimeric cyclodextrin. The Gibbs free energy changes (-deltaGo) for the unit
      increment per ethylene are 0.99 kJ mol(-1) for ANS and 0.44 kJmol(-1) for TNS,
      respectively. On the other hand, the presence of a copper(II) ion in
      metallobis(beta-cyclodextrin)s oligo(ethylenediamino) tethers enhances not only
      the original binding ability, but also the molecular selectivity through triple
      or multiple recognition, as compared with the parent bis(beta-cyclodextrin)s.

PMID- 11322556
TI  - Multiple use of soluble metallodendritic materials as catalysts and dyes.
AB  - Different sizes of core-functionalized metallodendritic wedges were prepared by
      anchoring sensor-active arylplatinum(II) sites at the focal point of Frechet-type
      polyether dendritic wedges of various generations. The strong color of these
      metallodendrimers in the presence of SO2 was used to assess the permeability of
      nanofiltration membranes (molecular weight cut-off of 400 dalton) at ambient
      pressure. A primary result of these studies is that dendrimers do not have to be
      exceptionally large for successful retention. Hence, nanofiltration, membrane
      capped. immersion vials were developed, which operate as sensor devices when
      loaded with metallodendrimers with good retention properties. Appropriate
      substitution of the dye site at the focal point of these metallodendritic wedges
      by a catalytically active group afforded dendritic catalysts that exhibit
      essentially the same physical properties (shape, retention) as the corresponding
      dyefunctionalized dendritic wedges. When this homogeneous catalyst is
      compartmentalized in membrane-capped vials, a unique and convenient method for
      its retrieval from product solutions is available. Moreover, such immobilized
      metallodendritic catalysts can be regenerated and stored for months without
      losing their activity; this provides access for the development of novel
      sustainable homogeneous catalysts.

PMID- 11322557
TI  - Cluster and periodic calculations of the ethene protonation reaction catalyzed by
      theta-1 zeolite: influence of method, model size, and structural constraints.
AB  - The protonation of ethene by three different acid sites of theta-1 zeolite was
      theoretically studied to analyze the extent and relevance of the following
      aspects of heterogeneous catalysis: the local geometry of the Bronsted acid site
      in a particular zeolite, the size of the cluster used to model the catalyst, the
      degree of geometry relaxation around the active site, and the effects related to
      medium- and long-range interactions between the reaction site and its
      environment. It has been found that while the reaction energy is very sensitive
      to the local geometry of the site, the activation energy is mainly affected by
      the methodology used and by electrostatic effects on account of the carbocationic
      nature of the transition state.

PMID- 11322558
TI  - Facial-selective allylation of methyl ketones for the asymmetric synthesis of
      alpha-substituted tertiary homoallylic ethers.
AB  - The asymmetric synthesis of enantiomerically pure a-substituted tertiary
      homoallylic ethers 4a, 11 and 12a-c by the allylation of ethyl methyl ketone (la)
      with gamma-substituted allylsilanes 9a-h is described. The allylsilanes were
      obtained by a nickel-catalysed Grignard cross-coupling reaction of (E)- and (Z)
      (3-iodoallyl)trimethylsilane with various Grignard reagents. The reaction of the
      allylsilanes with la in the presence of the trimethylsilyl ether of N
      trifluoroacetylnorpseudoephedrine (3), and catalytic amounts of a mixture of
      trimethylsilyl triflate and trifluoromethanesulfonic acid led to the homoallylic
      ethers 4a, 11 and 12a-c with two new stereogenic centres, with a selectivity of
      1:9 to >20:1 for the homoallylic and of 1:99 to >60:1 for the allylic centre. The
      facial selectivity does not depend on the configuration of the allylsilane, and
      in all reactions the anti product is preferentially formed. Interestingly, a
      pronounced switch of facial selectivity takes place with increasing length of the
      alkyl group of the allylsilane.

PMID- 11322559
TI  - Elimination of cross-talk and modulation of function in an organized
      heterosupramolecular assembly.
AB  - A close-packed monolayer of TiO2 nanocrystals was deposited on a conducting glass
      support using Langmuir-Blodgett (LB) techniques and fired. A close-packed mixed
      monolayer of eicosyl phosphonic acid (I) and the viologen. 1,1'-dieicosyl-4,4'
      bipyridinium dichloride (II) was then deposited on the TiO2 substrate, also using
      LB techniques. At sufficiently high dilutions of II in II a single viologen
      molecule is adsorbed with a known orientation at the surface of each nanocrystal.
      The resulting assembly was incorporated as the working electrode in an
      electrochemical cell. Under open circuit conditions, bandgap excitation of a TiO2
      nanocrystal results in electron transfer to a viologen molecule. No electron
      transfer between the viologen molecules adsorbed at different nanocrystals is
      observed. At a positive applied potential, electron transfer following bandgap
      excitation is largely suppressed. Considered are the implications of these
      findings for the development of practical devices based on modulatable function
      addressable on the nanometer scale.

PMID- 11322560
TI  - The pi complexation of alkali and alkaline earth ions by the use of meso
      octaalkylporphyrinogen and aromatic hydrocarbons.
AB  - The full metallation of meso-octaalkylporphyrinogens [R8N4H4] (R=Et, 1; nBu, 2;
      CH2Ph, 3; (CH2)4, 4) with heavy alkali metals (M = K, Rb, Cs) leads to the
      porphyrinogen-M4 compounds, in which the solvation of the alkali cations is
      largely assured by the intra- and intermolecular phi-interactions with the
      pyrrolyl anions. Such a mode of complexation results in a structural diversity as
      a function of the meso substituents, the size of the metal ion, and the solvent.
      The structure of the unsolvated polymers [R8N4M4]n (R= Et, M=K, 5; M=Rb, 6; M=Cs,
      7; R= (CH2)4, M = Rb, 8; M = Cs, 9) have been clarified through the X-ray
      analysis of 7 recrystallized from diglyme. The structure shows that the
      tetraanion binds two Cs ions inside the cavity, which display in one case
      eta1:eta1:eta1:eta1 and in the other eta5:eta5:eta5:eta5 interaction modes.
      Bidimensional polymerization is assured by four Cs ions, which each bind at the
      eta5 position on the exo face of each pyrrole. With bulkier meso substituents,
      different polymeric forms are obtained (R = nBu, M = K, 10; M = Rb, 11; M = Cs,
      12), and their structures were clarified through the X-ray analysis of 10, which
      was recrystallized from dimethoxyethane. The polymeric units are made up by the
      monomeric units [Bu8N4K2]2-, in which one potassium is eta1:eta1:eta1:eta5 and
      the other eta5:eta1:eta5:eta1 bonded inside the porphyrinogen cavity. In the case
      of R=CH2Ph, the monomeric anion [(PhCH2)8N4K2]2- (13) has been structurally
      identified. The metallation of 1 and 2 with active forms of alkaline earth metals
      (M' = Ca, Sr, Ba) led to dinuclear compounds [R,N4M'2] (R = Et, M' = Ca, 14;
      M'=Sr, 15; M'=Ba, 16; R=nBu. M'=Ba, 18), in which both metals inside the cavity
      are eta1:eta3:eta1:eta3 (Ca) and eta1:eta5:eta1:eta5 (Sr and Ba) bonded to the
      porphyrinogen tetraanion. The coordination sphere of each metal ion is completed
      by two THF molecules, which, in the case of Ba, are easily replaced by an arene
      ring [Bu8N4Ba2(eta6-arene)2] (arene=durene, 22; naphthalene, 23; toluene, 24;
      benzene, 25). The X-ray structures of 14, 15, 18, 22, and 23 are described in
      detail. We have tried to establish a relationship between the solid-state and
      solution structures by analyzing the 1H NMR spectra of the porphyrinogen
      complexes.

PMID- 11322561
TI  - Pt-tetraethynylethene molecular scaffolding: synthesis and characterization of a
      novel class of organometallic molecular rods.
AB  - The series of monodisperse Pt-bridged TEE oligomers 3a-f was prepared by
      oxidative Glaser-Hay oligomerization of monomer 7 under end-capping conditions.
      These novel molecular rods extend in length from 3.3 nm (monomeric 3a) to 12.1 nm
      (hexameric 3 f). Their isolation was achieved by high performance gel permeation
      chromatography (GPC), and their purification was best monitored by analytical GPC
      in combination with matrix-assisted laser-desorption-ionization mass spectrometry
      (MALDI-TOF MS). The mass spectra of each oligomer revealed the molecular ion or
      its sodium complex as parent ion together with a clean, highly characteristic
      fragmentation pattern. Delayed addition of the end-capping reagent PhC(triple
      bond)CH to the oligomerization mixture afforded polymer 10 with an average of
      approximately 32 repeat units and a remarkably narrow molecular weight
      distribution (Mw/Mn=1.06), which is indicative of a living polymerization
      process. UV/Vis spectral data as well as measurements of the second
      hyperpolarizability gamma by third harmonic generation (THG) revealed a nearly
      complete lack of pi-electron delocalization along the oligomeric backbone. The Pt
      atoms act as true insulating centers, and the Pt-C(sp) bonds hardly possess any
      pi character. The synthesis of the molecular rods 3a-f provides another
      demonstration of the power of oxidative acetylenic homocouplings for the
      preparation of unusual nanoarchitecture.

PMID- 11322562
TI  - Structural rearrangements in triple-decker-like complexes with mixed group 15/16
      ligands: synthesis and characterization of the redox couple.
AB  - The reaction of As4Se4 with stoichiometric amounts of [Cp*Fe2(CO)4] (Cp* = C5Me5)
      in boiling toluene forms [Cp2*Fe2As2Se2] (1) in good yield. X-ray crystallography
      shows 1 to have a triple-decker structure which comprises a tetraatomic mu,eta4:4
      As2Se2 ligand. Density functional theory (DFT) and extended Huckel molecular
      orbital (EHMO) calculations confirm that the As2Se2 ligand behaves as a four
      electron pi donor. Oxidation of 1 with equimolar amounts of [(C5H5)2Fe]PF6, Br2
      and I2, respectively, gave compounds 2-4. According to X-ray crystallographic
      investigations that were carried out on 2 and 4, the oxidation state has a
      considerable influence on the structure of the Fe2As2Se2 core: significant
      shortening of the Fe-Fe distance (deltad(Fe-Fe)> 0.3 A) and weakening of the As
      As bond length ((deltad(As-As) > 0.3 A) suggests the formal presence of two
      diatomic AsSe ligands and a Fe-Fe bond. DFT and EHMO calculations confirm that an
      electron is removed from an occupied Fe-Fe orbital of antibonding character
      during oxidation. All molecular orbitals lower their energies upon oxidation, but
      the energy drop is relatively small for those involving the As-As bond. An
      additional structural feature in 4 consists of an electronic interaction of the
      iodide with both As atoms which suggests a formally neutral ion pair.
      Electrochemical studies confirm that the oxidation of 1 is a reversible one
      electron process with E(1/2)= +0.07 V (in THF). These studies also reveal that 4
      dissociates in polar solvents, such as THF, into [1]+ and I-, which is followed
      by transformation into 1 and I3.

PMID- 11322563
TI  - Possible demographic influences on differentiating normal from aphasic
      performance.
AB  - To determine the psychometric validity of current language impairment,
      communication activity limitation, and quality of life measures for
      differentiating normal from chronically aphasic adults, we examined possible
      threats to test accuracy by the demographic variables age, educational level, and
      gender. A total of 18 chronically aphasic and 18 nonaphasic adults were evaluated
      with six measures. The results of correlational analyses indicated that, within
      the normal adult and aphasic adult groups, there exist significant relationships
      between some, but not all, demographic variables and performance on language
      impairment, communication activity limitation, and quality of life measures.
      Moreover, for certain variables, the strengths of these relationships differ
      significantly between normal and aphasic groups. Thus, adjustments in test scores
      or norms may be necessary to diagnose the presence or absence of aphasia.
      Otherwise, the tests' ability to differentiate between normal and aphasic adults
      may be compromised. EDUCATIONAL OBJECTIVES: Readers will be able to: (1) explain
      the relationship between test accuracy and psychometric validity; (2) state the
      direction of significant relationships (i.e., positive or negative) among
      demographic variables and test performance, within normal and aphasic adult
      groups; (3) explain necessary considerations in the adjustment of general test
      norms or scores based on a particular subject's age, education, or gender.

PMID- 11322564
TI  - Discourse sampling in the 21st century.
AB  - This paper examines the importance of evaluating discourse in individuals with a
      neurogenic language disorder. Discourse analysis is acknowledged as an important
      tool for speech-language pathologists, although it is often not the assessment
      tool of choice due to its apparent time-consuming nature and the overwhelming
      number of options available. The wide range of analyses available to clinicians
      such as the number of T-units and total words produced or Pragmatic Protocol
      checklists make it difficult to choose assessment measures. Even more difficult
      is the decision of where to direct treatment efforts. This paper aims to show
      that there are a number of levels of discourse analysis available to clinicians
      and that it is possible to sample a number of different genres in a clinical
      setting. The significance of the communication partner's contribution is
      discussed, particularly with regard to the limitations of the therapeutic
      interaction and the need to assess clients with a range of communication
      partners. The discourse opportunities we make available to people with
      communication problems will influence what is possible for them. To achieve this,
      the benefits of a theory of linguistic analysis, namely, Systemic Functional
      Linguistics (SFL) [Halliday, M. A. K. (1994). An introduction to functional
      grammar (2nd ed.). London: Edward Amold.] will be explored.

PMID- 11322565
TI  - Partner effects in adolescent conversations.
AB  - Twenty-four adolescents participated in social conversations with a same-sex
      peer, an opposite-sex peer, or a speech-language pathologist (SLP) or graduate
      student. The conversations were compared in regard to specific verbal and
      nonverbal behaviors, with the goal of identifying conversational behaviors that
      may be assessed with validity in a clinical setting. Significant differences were
      found in speaker and listener linguistic behaviors between conversations with
      peers and those with clinicians. A trend towards the increase in speaker
      nonverbal behaviors was also noted with clinician partners. Conversations with
      opposite-sex peers tended to be characterized by fewer direct questions, reduced
      listener eye contact, and increased listener nonverbal behaviors than those with
      same-sex peers. Several behaviors occurred rarely in any group, including
      physical contact between partners and requests for clarification; others occurred
      with high frequency in all groups, including eye contact and emotional
      expression. The implications of these patterns for persons with communication
      disorders are considered. EDUCATIONAL OBJECTIVES: (1) To describe communication
      behaviors that may be measured in adolescent conversations. (2) To identify those
      communication behaviors that may be influenced by factors related to the
      conversation partner.

PMID- 11322566
TI  - Evaluating treatment outcomes for adults who stutter.
AB  - The evaluation of stuttering treatment outcomes has traditionally focused
      primarily on changes in the production of speech disfluencies, even though many
      treatment approaches also address other aspects of the stuttering disorder, such
      as the speaker's reactions to stuttering and the overall effect of stuttering on
      the speaker's ability to communicate. One reason for the relative lack of
      outcomes data for many commonly recommended treatment programs is the fact that
      clinicians and researchers have not previously had access to a reliable means of
      assessing changes in the broader consequences of stuttering on a speaker's life.
      This paper describes an ongoing effort to develop a series of measurement
      instruments that can be used to evaluate the outcomes of a wide variety of
      stuttering treatment approaches by measuring changes in speakers' affective,
      behavioral, and cognitive reactions to stuttering; the effect of stuttering on
      speakers' functional communication abilities; and the impact of stuttering on
      speakers' overall quality of life.

PMID- 11322567
TI  - Identification of symptoms for spasmodic dysphonia and vocal tremor: a comparison
      of expert and nonexpert judges.
AB  - Spasmodic dysphonia is a rare voice disorder that is most successfully treated by
      injection of botulinum toxin (i.e., BOTOX) into the affected laryngeal muscles.
      BOTOX is currently available for use by professionals outside of metropolitan
      voice centers who may be unfamiliar with this rare disorder. Patients may seek
      assessment and treatment locally from clinicians who are unfamiliar with the
      speech symptoms for adductor-type (ADSD) or abductor-type (ABSD) spasmodic
      dysphonia. Although these disorders have been described in the literature, the
      symptoms have not been well defined and may appear similar to those of vocal
      tremor or muscle tension dysphonia (MTD). Thus, patients with spasmodic dysphonia
      might not be easily identified by local clinicians for treatment. The purpose of
      the current study was to determine whether voice clinicians with infrequent
      exposure to patients with spasmodic dysphonia could learn to identify speech
      symptoms for ADSD and ABSD comparable to voice clinicians with extensive
      experience with these disorders. The ratings of five nonexpert judges were
      compared to the ratings obtained from three expert judges. The results of this
      study demonstrated that nonexpert judges could be trained to identify the speech
      symptoms associated with ADSD, ABSD, and vocal tremor. While the nonexpert judges
      tended towards false positive judgements for the speech symptoms of interest, the
      overall speech symptom profiles for each type of voice disorder appeared
      comparable to those obtained from the expert judges. The symptom
      identificationscales used, therefore, have potential for use by clinicians
      unfamiliar with these disorders for correctly identifying persons with symptoms
      of ADSD and ABSD. EDUCATIONAL OBJECTIVES: Readers will be able to (1) define the
      predominant speech symptoms reflective of the voice disorder categories of ABSD,
      ADSD, and vocal tremor; and (2) describe the methods utilized in a new perceptual
      training protocol for teaching clinicians how to identify predominant speech
      symptoms associated with the voice disorder categories of ABSD, ADSD, and vocal
      tremor.

PMID- 11322568
TI  - Response generalization in apraxia of speech treatments: taking another look.
AB  - The purpose of the present paper is to present a critical review and reanalysis
      of response generalization effects in studies of treatment efficacy in apraxia of
      speech (AOS). Response generalization takes two forms: generalization of
      treatment effects to untrained exemplars of trained behaviors and generalization
      to untrained (i.e., novel) behaviors. In the past, response generalization has
      not been extensive and typically has been restricted to untrained exemplars of
      trained behaviors. Reasons for these findings are discussed with reference to
      recent advances in our understanding of the nature of AOS and to theories of
      speech motor control and teaming. The discussion focuses on the influence of the
      theoretical basis used to develop hypotheses and select behaviors to test
      predictions, the complexity of the treatment task/s, and patient characteristics.
      Suggestions for future directions in treatment efficacy research are offered.
      Learner outcomes: (1) An understanding of the nature of AOS, based on recent
      experimental analyses. (2) An understanding of the efficacy of current treatments
      for AOS in the area of response generalization. (3) An understanding of how
      theories of speech motor control might be applied to develop hypotheses for
      testing and increase effectiveness in treatment studies. (4) An understanding of
      how theories of speech motor control might guide selection of behaviors to test
      treatment effects and response generalization.

PMID- 11322569
TI  - An emergent account of language impairments in children with SLI: implications
      for assessment and intervention.
AB  - While current theoretical accounts of language impairments in children with
      specific language impairment (SLI) provide clear direction with regard to
      intervention goal setting, these same accounts say little with regard to the
      intervention process. Current developments in connectionist modeling and the
      extension of principles of dynamical systems theory to cognitive and language
      development have resulted in a new theory of language development known as
      emergentism. In contrast to traditional formal linguistic accounts, the
      emergentist view holds that language is a dynamic evolving system that can be
      represented as a distribution of probabilistic information. Language acquisition,
      from this perspective, emerges from the child's simultaneous integration of
      multiple acoustic, linguistic, social and communicative cues within the context
      of the communicative interaction. An alternative account of SLI grounded within
      this emergentist view is presented, and preliminary implications are explored
      with respect to assessment and intervention.

PMID- 11322570
TI  - Sensitivity and specificity of clinical/bedside examination signs for detecting
      aspiration in adults subsequent to stroke.
AB  - While detecting the presence of aspiration is only one aspect of a
      noninstrumented examination of swallowing function, it is an important component
      due to its potential health status consequences. The purpose of this
      investigation was to investigate the sensitivity and specificity of
      clinical/bedside examination signs for predicting aspiration on videofluoroscopic
      examination of swallowing. Sixty consecutive, acute stroke patients were
      investigated with clinical/bedside and videofluoroscopic exams. Clinical signs
      consisted of history, oral motor/speech praxis, voice, and trial swallow ratings.
      Results confirm that more work needs to be done if data collected from
      noninstrumented examinations are to be strongly predictive of aspiration on VFSE.
      However, comparisons of the current results with previous investigations provides
      a promising framework for future research. EDUCATIONAL OBJECTIVES: (1) To
      understand the use of sensitivity and specificity in detecting disease; (2) To
      understand the current evidence regarding clinical signs of aspiration.

PMID- 11322571
TI  - False belief understanding in children with specific language impairment.
AB  - Children's understanding that people's beliefs may differ from reality is an
      important milestone in cognitive development. Yet the tasks usually used to
      assess this understanding rely on the comprehension of complex syntax. Children
      with specific language impairment (SLI) have language abilities that are below
      age expectations, but their nonlinguistic cognitive abilities--crucial to false
      belief understanding--are closer to age level. Four conditions of a standard
      false belief task were administered to 10 children with SLI, 10 children of the
      same age, and 9 younger children whose language comprehension ability was similar
      to the children with SLI. The four conditions varied as to their linguistic
      complexity. The SLI group performed similarly to same-age peers when linguistic
      complexity was low, but similarly to younger children when linguistic complexity
      was high. These findings provide evidence that linguistic competence serves as a
      limiting factor in false belief performance for children with SLI. EDUCATIONAL
      OBJECTIVES: Readers will be able to (1) describe different hypotheses regarding
      the relationship between language and theory of mind development, (2) discuss how
      linguistic complexity impacts false belief performance for children with SLI, and
      (3) apply the language/theory of mind relationship when planning intervention.

PMID- 11322572
TI  - A comparison of relaxation training and syntax stimulation for chronic nonfluent
      aphasia.
AB  - This study examined the effects of relaxation training and syntax stimulation on
      the spoken language abilities of a 59-year-old male with chronic, nonfluent
      aphasia of moderate severity. Relaxation training consisted of progressive muscle
      relaxation (PMR) and guided imagery (GI), whereas the syntax stimulation was a
      modified version of the Helm Elicited Program for Syntax Stimulation (HELPSS)
      [(1981). Helm Elicited Language Program for Syntax Stimulation. Austin, TX: Pro
      Ed.]. These treatments were applied in the context of a single-subject
      alternating treatments plus baseline design. Results indicated that although both
      treatments produced improvements in spoken language, syntax stimulation was
      associated with larger improvements, particularly in terms of the proportions of
      grammatical utterances, correct information units (CIUs), and successful
      utterances produced by the participant. Analysis of treatment order, however,
      indicated that the participant's best performances of the syntax treatment and of
      the probe tasks occurred when relaxation training preceded syntax stimulation.
      These findings suggest that the simplicity and psychological benefits of
      relaxation training make it a complementary component to traditional linguistic
      programs for aphasia. EDUCATIONAL OBJECTIVES: (1) The reader will understand how
      psychological responses to stress may affect the language processing abilities of
      adults with aphasia. (2) The reader will be able to describe how relaxation
      training complements a traditional language treatment approach for remediating
      spoken language abilities of adults with chronic nonfluent aphasia.

PMID- 11322574
TI  - Relationship between extremities in motor performance.
AB  - The purpose of the study was to examine the relationship between the extremities
      in different aspects of motor performance, including simple reaction time, choice
      reaction time, speed of movement, tapping speed, and coordination, i.e., speed of
      movement/accuracy. 186 healthy randomly selected right-handed subjects (93 men,
      93 women; aged 21-70 years) were measured on a test battery of five tests for
      both hands and feet. Correlations between the extremities in motor performance
      were highest between hands (r=.71-.80, p<.001) or between feet (r=.57-.88,
      p<.001) depending on the complexity of response for all subjects. These relations
      remained at almost the same magnitude even when age was eliminated. Correlations
      between the upper and lower extremities were lower (r = .40-.62). Correlations
      between extremities were lower for one age group (21-30 years) than for all
      subjects (21-70 years). These results showed that the motor performance for the
      hands is not a very good indicator of the motor performance of the lower
      extremities, especially in a homogeneous age group, and it seems that the lower
      extremities should be studied with specific motor performance tests.

PMID- 11322573
TI  - Physical activity and sport involvement in French high school students.
AB  - The links between morphological, biological, sociological, psychological, and
      environmental characteristics, the practice of organized sports, and moderate to
      vigorous physical activities were examined by means of a questionnaire given to
      48 high-school students aged between 16 and 19 years and their continuous heart
      rate monitoring. Few correlations appear between these characteristics and
      moderate to vigorous physical activities. Only maximal oxygen uptake is linked to
      this type of activity in girls. Concerning sport involvement, correlations were
      more numerous for girls than boys. Physical and sports activities of girls were
      linked with maximal oxygen uptake, sport involvement of father, support, and
      encouragements of practice, perception of own activity, and private environment.
      Among boys, physical and sport activities were only linked with sport involvement
      of friends and perception of own activity. Unlike boys, physical and sport
      activities among girls seemed more strongly linked to sociological
      characteristics than other ones.

PMID- 11322575
TI  - Occupational physical activity as an indicator of health and fitness.
AB  - Recent government guidelines suggest that simply increasing physical activity,
      regardless of mode, leads to improved health profiles. This study examined the
      relationship between amount of work-related physical activity of United States
      Forest Service (USFS) workers and 12 indicators of health and fitness. Subjects
      were 110 USFS workers recruited from 8 separate USFS ranger stations in the
      Pacific Northwest. The associations between work-related physical activity and
      indicators of health and fitness indicated the 63 workers who were physically
      active on the job displayed better overall health and fitness patterns as
      evidenced by higher aerobic capacity, lower body fat, and greater muscular
      flexibility than their 47 inactive peers.

PMID- 11322576
TI  - Comparison of Body Mass Index by self-reported versus measured height and weight.
AB  - This study compared differences between self-reported and measured height and
      weight and subsequent Body Mass Index. College students (N=62) were asked to
      complete a health questionnaire as accurately as possible. Height and weight were
      self-reported without the knowledge that these variables would be subsequently
      measured. Self-reported and measured heights, weights, and calculated Body Mass
      Indexes were statistically compared. Analysis indicated that measured height was
      significantly less than self-reported height for men, but weight was not
      significantly different. Calculated Body Mass Index for men was not significantly
      different, however, self-reported Body Mass Index resulted in placement in the
      Normal range (18.5 to 24.9) category and measured Body Mass Index placement in
      the Overweight category (25.0 to 29.9). Women's self-reported and measured
      heights were not significantly different; however, self-reported weight was
      significantly less than measured. Further, significantly different Body Mass
      Indexes were found for women. It was concluded that self-reported height and
      weight might be viewed with caution in Body Mass Index assessment for convenience
      samples of college-age subjects.

PMID- 11322577
TI  - Homework in elementary physical education: a pilot study.
AB  - As physical education continues to decline in importance in the public school
      curriculum, it has become increasingly important for physical educators to
      provide opportunities for activity in nontraditional formats. This pilot study
      used a research design to examine the effects of homework in physical education.
      607 children in Grades 3, 4, and 5 participated. Independent t tests indicated
      that girls participated at a higher rate than boys and that there were no
      significant differences among grades. A one-way analysis of variance indicated a
      significant difference in rate of students' participation by class. A significant
      difference was also noted by month of the school year.

PMID- 11322578
TI  - Evaluation of sensorimotor training in children with ADHD.
AB  - Reduced ability to regulate motor behavior seems to be an essential aspect of
      Attention-Deficit Hyperactivity Disorder (ADHD) and may reflect deficits in
      behavioral response inhibition. In this respect, pragmatic clinical experience
      over the last two decades, in daily practice, training of motor control has
      played an important role within multimodal treatment approaches, although an
      adequate proof of its efficacy is still lacking. Therefore, to examine the
      efficacy of sensorimotor training, 12 children with ADHD (two groups of six) were
      treated with both sensorimotor training and (as control) cognitive behavioral
      training using a within-subject cross-over design. Each treatment had a duration
      of 4 months (20 sessions), yielding a total of 40 sessions for the completed
      cross-over design. Results showed that Sensorimotor Training improved
      sensorimotor coordination slightly, while Cognitive Behavioral Training
      ameliorated cognitive impulse control. Hyperactivity and anxious
      depressive/aggressive behavior were markedly reduced by Sensorimotor Training but
      not by Cognitive Behavioral Training. In conclusion, a combined treatment may be
      recommended since compensation and regulation of inhibitory deficits in ADHD come
      into play within the framework of both kinds of training.

PMID- 11322579
TI  - Adoption of hand-held dynamometry.
AB  - Published research indicates that hand-held dynamometry, a procedure for
      quantifying muscle strength, has increased in application over the past 15 years.
      The relationship between time and the number of research papers published is
      curvilinear, suggesting that the technology is still in its rapid adoption stage.

PMID- 11322580
TI  - Similarity and lightness effects in Ebbinghaus illusion created by keyboard
      characters.
AB  - 36 observers judged the size of a central S in variants of the Ebbinghaus figure
      having contextual Ss, $s, or Hs. When the figures were composed of similarly
      shaped elements, underestimation of the central S was obtained. Manipulations of
      lightness indicated that these underestimations were strongest for figures with
      gray contextual characters and a black central S and weakest for figures with
      black contextual characters and a gray central S. All black or all gray figures
      produced intermediate illusions. The data are consistent with Choplin and Medin's
      1999 claim that figural properties rather than semantic similarity influences
      size contrast and further show that the visual processes underlying size contrast
      include interactions of contours.

PMID- 11322581
TI  - Validity and reliability for the Bruininks-Oseretsky Test of Motor Proficiency
      Short Form as applied in the United Arab Emirates culture.
AB  - Validity and reliability of the Bruininks-Oseretsky Test of Motor Proficiency
      Short Form were examined through factor analysis, differences in motor
      proficiency among age groups, and internal consistency. The sample was comprised
      of 194 children (96 boys and 98 girls) of ages 6 to 11 years. A principal factor
      analysis solution with varimax rotation produced four factors: Gross and Fine
      Motor Skills, Eye-Hand Coordination, Balance-Coordination and Speed, and Visual
      motor Coordination. The loadings of these factors partially supported the
      theoretical work of Bruininks. Univariate analysis of variance showed significant
      differences between age groups either for each single item or for the total
      score. Correlation coefficients between single-item and total short form were all
      significant, although some values were relatively small. These results provided
      positive support for the construction and reliability of the test.

PMID- 11322582
TI  - Visual and haptic perception of the horizontal-vertical illusion.
AB  - The horizontal-vertical illusion consists of two lines of the same length (one
      horizontal and the other vertical) at a 90 degree angle from one another forming
      either an inverted-T or an L-shape. The illusion occurs when the length of a
      vertical line is perceived as longer than the horizontal line even though they
      are the same physical length. The illusion has been shown both visually and
      haptically. The present purpose was to assess differences between the visual or
      haptic perception of the illusions and also whether differences occur between the
      inverted-T and the L-shape illusions. The current study showed a greater effect
      in the haptic perception of the horizontal-vertical illusion than in visual
      perception. There is also greater illusory susceptibility of the inverted-T than
      the L-shape.

PMID- 11322583
TI  - At what age do children learn to discriminate between act and actor?
AB  - Children's ability to make moral judgements about an act on the basis of aspects
      of the act rather than on liking and preconceived ideas about the actor was
      investigated. 85 children of 4 age groups (preschool, Grades 1, 2, and 3, age
      range 5-9 years) participated. Act/Actor discrimination was investigated with a
      test consisting of 8 cartoons. In 4, a rabbit was behaving aggressively against a
      wolf; the other 4 portrayed identical acts with the wolf as aggressor and the
      rabbit as victim. Participants made moral evaluations of each cartoon. IQ was
      measured with Raven's Standard Progressive Matrices, and the general level of
      moral development was measured in accord with Piaget's (1932) criteria. Age, IQ,
      and general moral development correlated with discriminative ability for Act and
      Actor. In Piagetian terms, children at the heteronomous level were not capable of
      such discrimination, while children at the autonomous level (above 7 years of
      age) in general were.

PMID- 11322584
TI  - Observers' reaction to parent-child intimacy.
AB  - A study was carried out to examine how people react to acts of intimacy between
      parent and child. Based on an extensive series of studies reported in 1998 by
      Reis who found less intimate interactions between two men who are friends than
      between men or women or between two women who are friends, it was reasoned that
      intimacy between two males may violate norms of our culture, so it was predicted
      that people would react less favorably to intimacy between father and son than to
      intimacy between father and daughter, mother and daughter, or mother and son. Men
      (n = 19) and women (n=26), most of whom were 18-24 years of age, read versions of
      a mother or father having an intimate interaction (lap-sit, hair-stroke,
      hug/kiss) with an 11-yr.-old daughter or son and then rated the act on a 7-point
      scale from good to bad. As predicted, the undergraduates rated intimate
      interactions between father and son less favorably than those between father and
      daughter, mother and daughter, and mother and son.

PMID- 11322585
TI  - Geophysical variables and behavior: XCI. Ambulatory behavior in rats following
      prenatal exposures to complex magnetic fields designed to interact with genetic
      expression.
AB  - A total of 45 litters were exposed during their entire prenatal development to
      one of two complex patterns of magnetic fields whose strengths varied within one
      of four intensity ranges between 10 nT and 1,000 nT or to sham-field conditions.
      The litters exposed to the most complex pattern, composed of 50 200-msec.
      presentations of different pulses for 10 sec. every 50 sec., displayed more
      ambulation in an open field at 21 days of age than the litters that had been
      exposed continuously to a repetitive frequency-modulated field or to sham-field
      conditions. This treatment explained 25% of the variance in the numbers of
      squares traversed. The results suggest that complexity of the applied magnetic
      field during prenatal development may be more important than intensity for
      permanently affecting neuronal organization and behavior.

PMID- 11322586
TI  - Mental rotation and real-world wayfinding.
AB  - Sex differences in mental rotation skills are a robust finding in small-scale
      laboratory-based studies of spatial cognition. There is almost no evidence in the
      literature, however, relating these skills to performance on spatial tasks in
      large-scale, real-world activities such as navigating in a new city or in the
      woods. This study investigates the connections between mental rotation skills as
      measured by the Vandenburg-Kuse Mental Rotations test and the performance of
      college students (n=211) navigating a 6-km orienteering course. The results
      indicate that mental rotation skills are significantly correlated with wayfinding
      performance on an orienteering task. The findings also replicate sex differences
      in spatial ability as found in laboratory-scale studies. However, the findings
      complicate the discussion of mental rotation skills and sex because women often
      performed as well as men despite having lower mean test scores. This suggests
      that mental rotation ability may not be as necessary for some women's wayfinding
      as it is for men's navigation.

PMID- 11322587
TI  - Attribution of athletic expertise by college coaches.
AB  - The goals of the study were to identify the factors that college coaches
      associate with athletic achievement and to test deliberate practice theory
      predictions for practice relevance, effort, and pleasure. Swimming, tennis, and
      volleyball coaches from Division I and Division III schools rank ordered 15
      attributes that contribute to successful athletic achievement. They also rated
      the relevance, effort, and pleasure of 7 athletic and 7 everyday events for
      improving athletic achievement. The rank orders showed that the coaches primarily
      attributed athletic achievement to innate talent, intrinsic motivation, and
      effort while factors such as accumulated practice and type of the practice
      received lower rankings. Findings for practice effort were consistent with
      deliberate practice theory while the relevance and pleasure findings were mixed.
      Several explanations for successful athletic achievement, other than talent, are
      discussed.

PMID- 11322588
TI  - Partial response activation to masked primes is not dependent on response
      readiness.
AB  - Masked primes presented foveally prior to a target trigger an initial partial
      activation of their corresponding response, followed by an inhibition of the same
      response. The latter phase results in performance costs on compatible trials and
      performance benefits on incompatible trials relative to neutral trials (negative
      compatibility effect). The present study investigated whether this activation
      follow-by-inhibition process depends on the overall or specific state of response
      readiness. In two masked priming experiments, response readiness was manipulated
      by varying the relative frequency of Go-trials in a Go/NoGo task (Exp. 1) and the
      relative frequency of left- and right-hand responses in a 2-alternative choice
      reaction time task (Exp. 2). In both experiments, mean reaction times were longer
      for infrequent responses than for frequent responses. However, negative
      compatibility effects were not affected by response frequency. This result
      indicates that neither the general ability of masked primes to elicit a partial
      motor activation nor the specific time course of this process is dependent on
      response readiness. It is concluded that response readiness affects the execution
      of an overt response rather than the initial activation of this response.

PMID- 11322589
TI  - Does the body image exist in three dimensions? The study of visual mental
      representation of a body and a nonbody object.
AB  - Do the mental images of 3-dimensional objects recreate the depth characteristics
      of the original objects? This investigation of the characteristics of mental
      images utilized a novel boundary-detection task that required participants to
      relate a pair of crosses to the boundary of an image mentally projected onto a
      computer screen. 48 female participants with body attitudes within expected
      normal range were asked to image their own body and a familiar object from the
      front and the side. When the visual mental image was derived purely from long
      term memory, accuracy was better than chance for the front (64%) and side (63%)
      of the body and also for the front (55%) and side (68%) of the familiar nonbody
      object. This suggests that mental images containing depth and spatial information
      may be generated from information held in long-term memory. Pictorial exposure to
      views of the front or side of the objects was used to investigate the
      representations from which this 3-dimensional shape and size information is
      derived. The results are discussed in terms of three possible representational
      formats and argue that a front-view 2 1/2-dimensional representation mediates the
      transfer of information from long-term memory when depth information about the
      body is required.

PMID- 11322590
TI  - Spontaneous blinks as a criterion of visual fatigue during prolonged work on
      visual display terminals.
AB  - Visual fatigue caused by prolonged work viewing a Visual Display Terminals (VDT)
      and of work reading a hard-copy were assessed by electromyogram (EMG) waveform
      and electrooculogram (EOG) waveform in spontaneous blinks as objective criteria,
      and by questionnaire of subjective feeling, and by task performance. The duration
      and the amplitude of the EMG of the orbicularis ocular muscle on the right side
      and the EOG of the vertical direction to the eyelid were measured for 10 subjects
      who participated in a figure task consisting of the addition of single-digit
      numbers on a VDT work or a work with a hard-copy. The mean values of the duration
      and the amplitude of the EMG and the EOG were evaluated by the averaging of 10
      waveforms of the spontaneous blinks for all subjects. The time lag from the EMG
      to the EOG in the process of the generation of spontaneous blinks was also
      analyzed. These five parameters were evaluated during the work time. The mean
      values for the duration of the EMG increased gradually during the work time, but
      the amplitude did not show significant difference between the prework and a work
      time. There was no significant change of the duration of the EOG, but the mean
      amplitude of the EOG decreased as the work time progressed, and the time lag
      significantly extended. The blinks frequency increased relatively when using a
      VDT. The rate of fluctuation for these parameters was higher during use of a VDT
      than use of a hard-copy. The time lag at five hours of VDT work was extended by
      90% based on the value at the pre-work. The symptoms of general fatigue and
      fatigue of the eyes increased linearly during the VDT work for six hours. The
      results indicated a significant correlation between the objective parameters for
      the activity of the spontaneous blinks, i.e., duration and amplitude of EMG and
      EOG, and the time lag between EMG and EOG, and the subjective feeling was
      recognized in the time course of the task. These experimental results suggested
      that the parameters regarding the EMG and the EOG for the spontaneous blinks were
      effective indices for assessing visual fatigue during prolonged VDT work.

PMID- 11322591
TI  - The validity of role theory as an explanation of gender stereotypes: comment on
      Hosoda and Stone.
AB  - Hosoda and Stone note that role theory leads to the prediction that changes in
      women's roles should be followed by changes in gender stereotypes; however,
      having described changes in roles and observed stability in stereotypes, they do
      not draw the conclusion that their results are inconsistent with role theory.

PMID- 11322592
TI  - RPE responses during arm and leg exercises: effect of variations in spontaneously
      chosen crank rate.
AB  - The aim of this study was two-fold. First, the rating of perceived exertion (RPE)
      was compared between two different upper and lower body exercises. Subjects (n =
      12) performed with spontaneously chosen crank or pedal rates: (i) incremental
      maximum power tests (Test 1), with an initial work rate of 50% of maximal power
      followed by increases of 10% at each 120-sec. work stage and (ii) tests (Test 2)
      with exercise bouts set at 20, 40, 60, and 80% of maximal power separated by
      passive recovery periods. Second, the effects of variations in spontaneously
      chosen crank rate on RPE was analysed using the second test performed only with
      upper body. Subjects performed Test 2 three times with crank rates spontaneously
      chosen by the subjects, set at plus or minus 20% of spontaneously chosen crank
      rate. During both Tests 1 and 2 for upper or lower body, RPE increased linearly
      (p<.01) with power output. No significant difference was noticed between upper
      and lower body tests; however, RPE was significantly different (p<.05) between
      Test 1 results for upper and lower body at 70, 80, 90, and 100% of maximal power.
      The greater RPE at high power output could be linked to the important effect of
      fatigue during upper body exercise. Among the three crank-rate conditions, no
      significant difference in RPE was noticed. The choice of crank rate does not seem
      to influence the perception of exertion in upper body cycling exercise.

PMID- 11322593
TI  - Reaction to Compton and Metheny (2000): "assessment of grade inflation in higher
      education".
AB  - Comparison of grades awarded to all students in all courses at SUNY Geneseo in
      Spring 1990 and Spring 2000 shows a significant overall increase and a fairly
      stable pattern of grading practices across departments that resembles the pattern
      reported by Compton and Metheny in 2000 and other investigators.

PMID- 11322594
TI  - Source of improvement in balance control after a training program for ankle
      proprioception.
AB  - Previous research on healthy individuals reported improvements in balance control
      following a purported ankle proprioception-training program. The training may
      have resulted in a general rather than a specific enhancement of ankle
      proprioception. To test this hypothesis, subjects were constrained at the hips
      and trunk with a custom-made thoracolumbosacral orthosis and performed a one-leg
      standing test with eyes closed and head tilted back, so that they had to rely
      primarily on their ankle musculature to keep their balance. Subjects were
      retested after training on the BAPS three times a week for 4 weeks, following the
      training recommendations of the manual. Subjects' bodies were not constrained
      during the training. Analysis showed that subjects made improvements during
      training in performing more difficult tasks on the board. On the one-leg test,
      however, there were no improvements in sway velocity, number of touchdowns, or
      falls relative to pretest scores. Improvements observed during training likely
      resulted from diffuse enhancement of proprioception in other body segments such
      as the knees, hips, spine, and upper extremities. A training program in control
      of general balance does not specifically target ankle proprioception.

PMID- 11322595
TI  - Hemispheric processing characteristics for lexical decisions in adults with
      reading disorders.
AB  - The present study measured unilateral tachistoscopic vocal reaction times and
      error responses of reading-disordered and normally reading adults to single words
      and nonwords in a series of lexical decision tasks at two linguistic levels
      (concrete and abstract words). Analysis of variance on reaction times indicated
      that main effects of stimulus type, visual field, and the interaction of these
      variables were not significant for the reading-disordered group, but visual field
      and an interaction of visual field and stimulus type were for the normally
      reading adults. Error rate showed a significant interaction of stimulus x visual
      field for the reading-disordered group but not for the normal reading group. Post
      hoc tests showed significant differences in error rates between visual fields for
      concrete lexicon but not for abstract or nonsense lexicon for the reading
      disordered group. These findings suggest a deficit in interhemispheric lexical
      transfer occurs for reading-disordered samples and suggest use of a callosal
      relay model wherein the left hemisphere is allocated responsibility for
      performing central operations underlying lexical decisions by adults with reading
      disorders.

PMID- 11322596
TI  - Effects of increasing expenditure of energy during exercise on psychological well
      being in older adults.
AB  - The purpose of present study was to examine the effects on psychological well
      being of energy expended as a result of the exercise intervention. 33 older
      adults (M age=68.6 yr., SD=4.7) participated in three supervised water-based
      exercise sessions per week for 12 wk. Based on the relative changes in daily
      energy expenditure as measured by questionnaire between pre- and posttraining,
      the subjects were split into three groups. This classified each subject as either
      having experienced a relatively low change (n=11), moderate change (n= 11), or
      high change (n= 11) in daily energy expenditure. Our data showed that the group
      with the greater increase in energy expenditure as a result of exercise, when
      compared pre- and posttraining, improved only on Depression-Dejection on the
      Profile of Mood States more than did the group with low change. Consequently, we
      concluded that the amount of energy expended was partially related to improvement
      in psychological well-being.

PMID- 11322597
TI  - Reply to Fudin and Lembessis's critique of Malik and Paraherakis's commentary
      regarding the capacity of the unconscious.
AB  - In an earlier paper, we had suggested that the research examining the capacity of
      the unconscious cannot be interpreted unambiguously to make the claim that the
      unconscious is limited in scope. Fudin and Lembessis challenged our conclusion,
      and we address their concerns.

PMID- 11322598
TI  - On weighted exponential entropies.
AB  - As an alternative to Shannon's classical entropy measure of information, an
      exponential entropy function was proposed by Pal and Pal in 1989 and 1991. To
      generalize Pal's entropy further, this author introduced two different families
      of exponential entropies that are one-parameter generalizations of Pal's entropy.
      The purpose of the present paper is to define weighted entropies corresponding to
      those one-parameter generalizations. Some properties and examples of such
      weighted exponential entropies are discussed.

PMID- 11322599
TI  - Retention of relative force in the scaling of a serial force pattern with an
      attenuated-force tap.
AB  - The present study was designed to examine the retention of relative force in the
      scaling of a serial force pattern in a finger-tapping sequence using an
      attenuated tap. On practice trials, 12 undergraduate students tapped a force
      plate connected to strain gauges that gave them feedback about the force. On test
      trials, participants recalled the force pattern (200 gm-200 gm-200 gm-100 gm) and
      the intertap interval (400 msec.) practiced during the practice period without
      the feedback (recalled task). Then, they adaptively produced a halved (halved
      task) or doubled force profile (doubled task) at the fixed intertap interval.
      Analyses showed that mean peak forces at the first three tap positions of the
      tapping sequence undershot the expected forces across all tasks. Hence, the
      ratios of the forces in Serial Positions 1:4, 2:4, and 3:4 were considerably
      lower than 2.0. This is a contextual effect suggesting that the last attenuated
      tap affected the first three taps of the tapping sequence. Thus, because the
      relative force of movements appears to be a weaker invariant feature than
      sequencing and relative timing for generalized motor program theory of Schmidt
      and Lee, this finding does not support the relative force for a generalized motor
      program.

PMID- 11322600
TI  - Self-talk in a basketball-shooting task.
AB  - This study examined the effectiveness of two different types of self-talk on the
      performance of a basketball-shooting task. 60 physical education and sports
      sciences students were organized into one control and two treatment groups which
      used self-talk. During the experiment, the control group performed with the
      general instructions, whereas the self-talk groups used the cue-words "relax" and
      "fast," respectively, Analysis showed that only the participants of the self-talk
      group who used the word "relax" improved their performance significantly as
      compared to the other two groups. It appears that self-talk can positively affect
      performance if its content is appropriate for the task performed.

PMID- 11322601
TI  - Speech-sounds perception test: long- and short-forms reliability adjusted for
      item difficulty.
AB  - The internal consistency reliability of the Speech-Sounds Perception Test was
      computed for the long form (.9159), short form (.8410), and the six series (.6109
      to .7310). The total sample (N= 632) consisted of normal, diffusely brain
      damaged, and undiagnosed patients referred for assessment.

PMID- 11322602
TI  - Perception of time: variations in verbal content and delay of estimation.
AB  - Delay of time estimation results in consistently longer judgments than immediate
      estimation, yet confirmatory studies have relied primarily on numerical digits
      for interpolated material as shown, for example, by Vitulli and Rowe in 1999. The
      present study used three paragraphs audiotaped from a 1998 textbook in general
      psychology by Baron as stimuli presented for judgment of the passage of time.
      Among 218 undergraduate volunteers delay of estimation produced significantly
      longer judgments regardless of the verbal passage, and short-term memory scores
      varied as a function of content.

PMID- 11322603
TI  - Experiences of spiritual visitation and impregnation: potential induction by
      frequency-modulated transients from an adjacent clock.
AB  - A left-handed Roman Catholic female adolescent with a history of early brain
      trauma reported nightly visitations by a sentient being. During one episode she
      experienced vibrations of the bed, an external presence along the left side that
      moved into her body, inner vaginal (not clitoral) and uterine sensations, and the
      sense of being impregnated by a force she attributed to the Holy Spirit. After
      the latter experience she felt an invisible baby superimposed upon her left
      shoulder. Analyses of the measurements for magnetic anomalies within her bedroom
      indicated an electric clock about 20 cm from her head while she slept. The
      complex form of the 4 microT magnetic pulses generated by the clock was similar
      to shapes that evoke electrical seizures in epileptic rats and sensitive humans.

PMID- 11322604
TI  - Accuracy of two simple methods for the assessment of health-related physical
      fitness.
AB  - We have developed a useful equation for estimating health-related physical
      fitness age. This version of health-related fitness age was developed as an
      extension of the biological age index and is useful for evaluation of individual
      differences in functional abilities of middle-aged and older adults. This measure
      consists of 4 independent variables fitness (VO2 max, standing trunk flexibility,
      %fat, and grip strength). However, direct measurement of maximal oxygen uptake
      (VO2 max) is an invasive clinical procedure and not practical for large scale
      work. In the current study, we attempted to assess the fitness age more feasibly.
      We selected a questionnaire method and a 12-min. submaximal treadmill walk test
      as substitutes for the VO2 max test. The three fitness ages were computed for 23
      Japanese men (M(age) 54.7 +/- 10.7 yr.), using actual VO2 max (actual fitness
      age), questionnaire VO2 max (predicted questionnaire fitness age), and treadmill
      VO2 max (predicted treadmill fitness age). Predicted questionnaire fitness age
      (61.0 +/- 10.5 yr.) and predicted treadmill fitness age (60.0 +/- 12.4 yr.) were
      significantly correlated with actual fitness age (60.1 +/- 12.4 yr.) (r= .96 and
      .97, respectively). There were no significant differences among the three
      indices, but there was a significant difference between actual fitness age and
      chronological age (p<.05). For VO+/-2 max substituting the questionnaire for the
      treadmill estimate is acceptable in assessing fitness age and reducing the
      clinical risk for middle-aged and older Japanese men.

PMID- 11322605
TI  - Shifting gustatory thresholds and food cravings during pregnancy as expanding
      uterine-induced steady potential shifts within the insula: an hypothesis.
AB  - A logical extrapolation from the principle that structure dictates function is
      that transient or anomalous experiences are consequences of simultaneous
      stimulations of proximal brain regions not typically co-activated. In this paper
      the occasional shifts in gustatory threshold during the menstrual cycle, the
      craving for unusual tastes experienced by some during pregnancies, and, the
      reports by postmenopausal women of the "burning mouth syndrome" are hypothesized
      to be artifacts of the proximity of gustatory and uterine representations within
      the female insula. Transient (menstrual) or tonic (pregnancy) stimulation within
      the uterus might shift the locus of neuronal activity within the insula to
      include adjacent gustatory neurons and consequently alter taste experiences.
      Specific tests of this hypothesis are suggested.

PMID- 11322606
TI  - Psychosocial factors, workload, and human error in a simulated pharmacy
      dispensing task.
AB  - Participants filled 42 orders on a task designed to simulate components of
      filling prescriptions. Task factors included objective workload of 70- versus 80
      min. to complete the task and perceptions of workload dimensions using the NASA
      Task Load Index. The proportion and pattern of data-entry, counting, and product
      selection errors were compatible with those found in pharmacy field-sites.
      Significant other relationship stress, field-dependence, and an 80-min. workpace
      predicted data-entry errors. Mistakes in product selection were associated with
      low GPA, high social stress, the NASA Task Load Index dimension of less concern
      with performing well, and a 70-min. workpace. Relationship of data to
      corresponding information in the pharmacy literature and to assumptions of a
      cognitive-systems performance model was discussed.

PMID- 11322607
TI  - Prediction of drivers' recognition of posted signs in five Arab countries.
AB  - The effects of six predictor variables, drivers' age, monthly income, years of
      education, sex, marital status, and nationality on perception of traffic signs
      were modeled through regression techniques. The populations sampled here were
      from Kuwait, United Arab Emirates, Bahrain, Qatar, and Oman. A total of 28 posted
      regulatory and warning signs were investigated. A questionnaire especially
      prepared for this study was distributed to 9,000 drivers in the five states, out
      of which 4,774 responded (53%). The drivers were selected according to stratified
      choice-based random sampling technique. Two prediction models were developed for
      assessment of drivers' recognition of regulatory and warning signs.

PMID- 11322608
TI  - Identification of twins by spoken syllables.
AB  - It is shown that the results of an experiment on speaker identification described
      by Whiteside and Rixon in 2000 seem to be contradictory and inconclusive. To
      investigate whether the experiment allows reliable conclusions, re-evaluation of
      their data using multiple regression techniques is proposed.

PMID- 11322609
TI  - Supporting independent indoor travel of people with blindness and intellectual
      disability with reduced frequencies of auditory cues.
AB  - This study evaluated the feasibility of supporting independent indoor travel
      using reduced frequencies of auditory cues with two persons having total
      blindness and profound intellectual disability. For these persons, who had
      acquired satisfactory travel performance with cues occurring every 8 sec., the
      cue frequencies were reduced to one-half or one-third of the original level.
      Analysis showed that both participants could manage accurate travel under the new
      cue conditions, even though their travel time (efficiency) seemed negatively
      affected. Implications of the findings were discussed.

PMID- 11322610
TI  - Memorization of young people under loud pink noise of short duration.
AB  - Exposure of students to loud pink noise of short duration in schools with high
      background noise showed that memorization of the students under loud pink noise
      is correlated with noise level. For levels up to 91.5 dB(A) the performance of
      275 students improved, but for louder noise performance was reduced.

PMID- 11322611
TI  - Brief successive temporal observational sampling as a possible indicator of daily
      overt seizure activity in epileptic rats.
AB  - Chronic, limbic epilepsy was induced in male rats by a single systemic injection
      of lithium and pilocarpine. In two separate experiments, each 6 mo. in duration,
      the proportion of the population that displayed an overt motor seizure (head
      nodding, rearing, and forelimb clonus) within 10 min. each day after delivery of
      food pellets (despite food provided ad libitum) was recorded. Cumulative records
      for the numbers of rats in each population that displayed overt seizure for the
      first time during the observation period were plotted as a function of time. The
      occurrence of the saturated (approaching 100%) asymptote at about five months was
      interpreted to indicate that brief (10 min.) sampling over the 144 successive
      days that would compose a single 24-hr. period could serve as an estimate of the
      average probability of an overt seizure during an average 24-hr. period. If this
      assumption is correct, then these rats would have displayed about one overt
      seizure per day.

PMID- 11322612
TI  - Brainstem frequency-following response recorded from one vertical and three
      horizontal electrode derivations.
AB  - The human brainstem frequency-following response reflects neural activity to
      periodic auditory stimuli. Responses were simultaneously recorded from one
      vertically oriented and three horizontally oriented electrode derivations. Nine
      participants each received a total of 16,000 tone repetitions, 4,000 for each of
      four stimulus frequencies: 222, 266, 350, and 450 Hz. The responses were
      digitally filtered, quantified by correlation and spectral analysis, and
      statistically evaluated by repeated measure analysis of variance. While the
      various horizontal derivation responses did not differ from each other in latency
      (values tightly clustered around M= 2.60 msec.), the vertical derivation response
      occurred significantly later (M=4.38 msec.). The smaller latency for the
      horizontal responses suggests an origin within the acoustic nerve, while the
      larger latency for the vertical response suggests a central brainstem origin. The
      largest response amplitude resulted from gold "tiptrode" electrodes placed in
      each auditory meatus, suggesting that this electrode derivation provided the most
      accurate (noninvasive) assessment of short-latency events originating at the
      level of the auditory nerve.

PMID- 11322613
TI  - 2000 Research Laureate Medallion Award.

PMID- 11322614
TI  - From research to "best practices" in other settings and populations.
AB  - OBJECTIVE: To review the genesis and current status of best practices" thinking,
      its application in health promotion practice, and in generalizing research to
      alternate populations, places and times. METHODS: A presbyopic eye is cast over
      the recent evolution of the concept of "best practices" from medicine to public
      health. RESULTS: Some discontinuities are found in the migration of this concept
      from medicine, where it applies with some consistency to the relatively
      homogeneous physiology of the human species, to health behaviorwhere social,
      cultural, economic, and other heterogeneities make the generalizability of any
      research more suspect. CONCLUSIONS: Health promotion and other applications of
      health behavioral research need to replace "best practices" with "best
      processes."

PMID- 11322615
TI  - Pharmacologic treatments for the nicotine dependent smoker.
AB  - OBJECTIVE: To explore the biology of nicotine addiction and to investigate the
      latest pharmacological treatments for nicotine dependence. METHODS: Explore the
      research literature for treating nicotine dependence. RESULTS: Nicotine is an
      additive drug and the most effective methods for treating dependence are nicotine
      replacement therapy (NRT) and bupropion SR. CONCLUSION: The best available
      treatments for nicotine dependence are pharmacological adjuncts; specifically,
      NRT and bupropion SR when combined with behavioral counseling.

PMID- 11322616
TI  - Advancing the science of adolescent tobacco use cessation.
AB  - OBJECTIVE: To examine how science is advancing in order to address adolescent
      tobacco use cessation. METHODS: Review of the published scientific literature
      from 1995 to September 2000 and National Cancer Institute youth tobacco cessation
      research portfolio. RESULTS: Because of methodological limitations, results of
      behavioral interventions are inconclusive. Two studies have been published
      evaluating the nicotine patch for adolescent smoking cessation, though neither
      employed a randomized, placebo-control design. Both of these studies found the
      nicotine patch to be ineffective. CONCLUSIONS: Although much is known about youth
      tobacco use, additional research is needed to find answers to best help youth to
      quit smoking.

PMID- 11322617
TI  - School-based tobacco use prevention and cessation: where are we going?
AB  - OBJECTIVE: To discuss the past, present, and future directions of school-based
      tobacco use prevention and cessation research. METHODS: Discuss the origins of
      tobacco use prevention research; how prevention research advanced with empirical
      etiologic work; the genesis of comprehensive social influences programming and
      its contents; multiple modalities of programming beyond the school setting; and
      the rebirth of teen cessation programming and the issue of dissemination.
      RESULTS: There are many avenues of teen tobacco use prevention and cessation
      research and practice that need continued exploration, particularly regarding
      effects mediation and teen cessation. CONCLUSIONS: This discussion provides a
      background to assist health behavior researchers and practitioners to move
      forward in this arena.

PMID- 11322618
TI  - Preventing smoking in multiethnic communities.
AB  - OBJECTIVE: To examine community-based efforts to prevent tobacco use among
      adolescents, compared and contrasted to efforts conducted in schools. METHODS:
      Review effective school-based prevention efforts including the Surgeon General's
      research reports describing broader based community approaches. RESULTS: By
      reducing illegal sales, making it physically more difficult to purchase and
      consume tobacco, promoting nonuse and increasing the price of cigarettes via
      other policy changes, and using aggressive media spots to complement these
      community changes, we can shift this focus back to the industry and allied
      political and economic interests. CONCLUSION: By adopting specific approaches,
      further reductions in the stubbornly stable adolescent prevalence rates can be
      realized.

PMID- 11322619
TI  - Preventive alcohol interventions based on a stages of acquisition model.
AB  - OBJECTIVE: To examine the promise and pitfalls of using multi-component
      motivational stages framework for tailoring alcohol prevention programs. METHODS:
      Review empirical research examining intra-drug-use stages of acquisition and
      testing the efficacy of stage-tailored interventions. RESULTS: Seven cross
      sectional studies suggest that youth exist within a range of stages of alcohol
      acquisition. Five randomized trials showed that stage-based preventive
      interventions resulted in significant alcohol reductions. CONCLUSIONS:
      Recommendations for future stage-related prevention research and practice are
      discussed.

PMID- 11322620
TI  - The role of feedback in the process of health behavior change.
AB  - OBJECTIVE: To offer a taxonomy of types of feedback and describe potential
      mechanisms of action particularly in the area of addictive behaviors. METHOD:
      Reviewed the literature to examine support for types-Generic, Targeted, and
      Personalized-and for mechanisms of feedback. RESULTS: Although it is not clear
      how it works, feedback is thought to offer important information, to create a
      sense of caring and helping relationship, to reach more directly decisional
      considerations, to increase engagement in the materials, to increase motivation,
      or to provide social comparison and norms. CONCLUSIONS: Avenues for future
      research in search of the most effective manner of using feedback to promote
      health behavior change are discussed.

PMID- 11322621
TI  - The future of health behavior and prevention research: what will change in the
      next 25 years?
AB  - OBJECTIVE: To review progress in the field of health behavior research and
      suggest future directions. METHODS: Reviewed the theoretical and methodological
      underpinnings of research during the past 25 years and identified likely
      technological changes that will impact research during the next 25 years.
      RESULTS: In the not-too-distant future, normal science will be transformed by
      broad-based diffusion of innovations, some of which will include the increased
      use of automated data collection methods and the widespread adoption of research
      based programs. CONCLUSION: Research during the next 25 years will eventually
      result in a radical transformation of health behavior research.

PMID- 11322622
TI  - Community prevention trials: a respectful partnership.
AB  - OBJECTIVE: To review the theoretical basis for a systems approach to community
      prevention of alcohol problems and the policy options that this approach
      suggests. METHOD: A community systems prevention project used 4 environmental
      strategies to reduce heavy drinking. RESULTS: The Community Trial, using an
      environmental approach to prevention, achieved a statistically significant
      reduction in alcohol-involved traffic crashes in addition to lower sales of
      alcohol to young people and greater number of policies against serving alcohol to
      intoxicated persons. CONCLUSION: This trial demonstrated that a respectful
      partnership between researchers and community members is essential. Prevention
      planners and policy makers must understand how various aspects of the community
      influence alcohol and other drug use, thereby contributing to alcohol and other
      drug problems.

PMID- 11322623
TI  - Nutrition interventions for low-income, elderly women.
AB  - OBJECTIVE: To help low-income, older South Carolinian women bring their food
      choices and nutritional practices in closer alignment with broadly accepted
      recommendations for healthful eating. METHODS: Included the creation of an
      infrastructure of collaborators to examine existing data, develop research
      questions, and collect and analyze focus group data. RESULTS: Include
      identification of socioenvironmental, personal, and behavioral factors affecting
      the nutritional health of elderly women used in the development of nutrition
      education modules and messages to be delivered through lay educators and videos.
      CONCLUSION: Effective nutrition interventions involving low-income, elderly women
      must use an ecological approach including behavioral and organizational change.

PMID- 11322624
TI  - Public health strategies for obesity treatment and prevention.
AB  - OBJECTIVE: To review research on public health interventions for obesity.
      METHODS: Describe recent changes in obesity prevalence in the United States and 5
      research studies from the University of Minnesota directed at the problem.
      RESULTS: The prevalence of obesity has increased dramatically over the last 15
      years. CONCLUSIONS: Recent increases in obesity in the United States have been of
      great concern for public health. Health education approaches to addressing the
      problem have not been effective. It is suggested that alternative approaches,
      such as changing the price structure of foods, may be necessary if the problem is
      to be successfully addressed.

PMID- 11322625
TI  - Using social marketing to develop and test tailored health messages.
AB  - OBJECTIVE: To advance and promote procedures to evaluate tailored health messages
      based on the 4 Ps of social marketing (SM). METHOD: Three studies are presented
      for heuristic purposes to show the evolution and application of a "research plan"
      to 3 phases of SM research that address the 4 Ps. RESULTS: Qualitative and
      quantitative methods provide useful information to develop messages and to
      evaluate message efficacy for public health campaigns, to recruit participants to
      interventions, and/or to influence program adherence and participant retention.
      CONCLUSIONS: Formal, systematic research methods offer a viable means to evaluate
      the potential of SM constructs.

PMID- 11322626
TI  - The Youth Risk Behavior Surveillance System: measuring health-risk behaviors.
AB  - OBJECTIVE: To measure priority health-riskbehaviors among youth. METHODS: The
      Youth Risk Behavior Surveillance System (YRBSS) monitors priority health-risk
      behaviors among youth. RESULTS: In 1999, many high school students practiced
      behaviors that contribute to leading health problems--16.4% rarely or never wore
      safety belts and, during the past 30 days, 17.3% carried a weapon, 34.8% smoked
      cigarettes, and 26.7% used marijuana. Also, 49.9% had had sexual intercourse. One
      quarter (26.0%) were at risk for becoming overweight or were overweight.
      CONCLUSION: YRBSS data are used to improve policies and programs to reduce
      priority health-risk behaviors among youth.

PMID- 11322627
TI  - Modeling categorical variables by logistic regression.
AB  - OBJECTIVE: To demonstrate the use of logistic regression in health care research.
      METHOD: Forward and backward stepwise logistic regression algorithms were
      systematically applied to a real-world data set comprising 301 cancer patients
      and a set of explanatory variables. RESULTS: Four variables were identified as
      effective predictors of pain reporting by cancer patients during chemotherapy:
      fatigue, depression, severity of colds or viral infections, and insomnia. The 4
      predictor model was validated by (a) significance tests of regression
      coefficients at p<0.05, (b) significant improvement of this model over competing
      models, and (c) goodness of fit indices. CONCLUSIONS: Logistic regression is
      useful for health-related research in which outcomes of interest are often
      categorical.

PMID- 11322628
TI  - Data mining and healthcare informatics.
AB  - OBJECTIVE: To acquaint members of the Academy with a relatively recent
      development in the area of data exploration and statistical analysis. METHODS: A
      review of the concepts and methods inherent in data-mining with a special
      emphasis on the those methods applicable to predictive modeling. RESULTS: Data
      mining is demonstrated to be a useful tool for researchers in those circumstances
      where large amounts of information are available. CONCLUSIONS: With the advent
      and proliferation of on-line data collection, truly massive databases are now
      available to health care researchers. In that situation, data-mining methods
      yield some unique opportunities to researchers who wish to develop prediction
      models and to establish associations.

PMID- 11322629
TI  - Health attitude scale construction: importance of psychometric evidence.
AB  - OBJECTIVE: To identify 18 steps to 3-component attitude scale construction.
      METHODS: Examples are provided to illustrate each step. RESULTS: The presentation
      primarily focused on specific steps in constructing meaningful health attitude
      scales. Further, the importance and concept of various forms of realibilty and
      validity are provided. Special attention is given to factors affectiving
      psychometric evidence. CONCLUSIONS: In order to meaningfully measure health
      related attitudes, researchers and evaluators should consider following the steps
      outline in the presentation.

PMID- 11322630
TI  - Importance of health education research to health education.
AB  - OBJECTIVE: To focus on the benefits and importance of research to the practice of
      health education. METHODS: The paper discussed the potential of quality research
      as well as the barriers that keep health educators from using, applying, and
      sharing their work. RESULTS: The basic challenges health educators face in
      translating their research into practice relate to: becoming well-versed in the
      science base and previous lessons learned; collaborating effectively; and passing
      on knowledge by mentoring. CONCLUSIONS: To move forward, health educators need to
      organize their knowledge and make it accessible. This includes explicit and tacit
      knowledge, work in progress, and a coordinated research agenda. Finally, health
      educators need to be flexible so they can enable future research needs.

PMID- 11322631
TI  - The American Academy of Health Behavior--an organization whose time has come.

PMID- 11322632
TI  - Effects of nitric oxide donors and nitric oxide synthase substrates on ciliary
      muscle contracted by carbachol and endothelin for possible use in myopia
      prevention.
AB  - Research has suggested that the development of myopia may possibly be prevented
      by the use of drugs which facilitate relaxation of the intraocular ciliary
      muscle. We examined the effects of five nitric oxide-producing agents--two nitric
      oxide donors, hydralazine and sodium nitrite, and three nitric oxide synthase
      substrates, L-arginine, L-canavanine, and N-benzoyl-L-arginine ethyl ester--on
      isolated bovine ciliary muscle maximally contracted with either carbachol or
      endothelin-1. Of these agents, hydralazine and L-canavanine produced a relaxing
      effect on endothelin-1-contracted muscle that was significantly greater than
      relaxing effect on carbachol-contracted muscle. These results indicate that
      hydralazine and L-canavanine could possibly be used for the prevention of myopia
      by relaxing the ciliary muscle with few anticholinergic and cycloplegic side
      effects.

PMID- 11322633
TI  - Effects of dopamine antagonists in human eye accommodation.
AB  - The purpose of this study was to evaluate the effects of dopamine antagonists in
      accommodation of the human eye. The dopamine antagonist drugs used in this
      experiment include 0.5% metoclopramide and 0.25% droperidol. Eighteen healthy
      subjects were enrolled; they were randomly assigned, in double-masked fashion, to
      receive topical administration of a single drop of either 0.5% metoclopramide or
      0.25% droperidol in one eye, with the fellow eye receiving isotonic saline as
      control. The accommodative abilities of both eyes were measured before
      instillation, and also at 3 and 6 hr after instillation of drugs, respectively.
      We studied the latency of reaction, the rate of accommodation, the average
      accommodative power, the rate of recovering and the total recovering time as the
      five parameters for evaluating the accommodative ability of each eye. The results
      showed that there were significant changes in two parameters: the rate of
      accommodation and rate of recovering, whereas there were no significant changes
      in the other three parameters: latency of accommodation, average power of
      accommodation and total recovering time. In conclusion, the dopamine antagonists
      may have some effects on the rate of accommodation but not the degree of
      accommodation. Further studies with higher concentrations of these dopamine
      antagonists on dose-response relationships are needed before exact drug efficacy
      can be drawn.

PMID- 11322634
TI  - Intraocular pressure-lowering efficacy of latanoprost in patients with normal
      tension glaucoma or primary open-angle glaucoma.
AB  - We investigated the intraocular pressure (IOP)-lowering potential of latanoprost
      in patients with normal-tension glaucoma (NTG) or primary open-angle glaucoma
      (POAG). This prospective study included 59 NTG and 20 POAG patients treated with
      the following four dosing regimens of latanoprost: patients on no previous
      medication received latanoprost as initial therapy (Group 1, n=31), patients on
      beta-blocker therapy received latanoprost as adjunctive therapy (Group II, n=9),
      patients on unoprostone monotherapy were switched to latanoprost monotherapy
      (Group III, n=14), and patients previously on dual therapy with isopropyl
      unoprostone and beta-blocker were switched to a combined treatment of latanoprost
      and beta-blocker (Group IV, n=25). IOP significantly decreased 8 weeks after
      initiation of latanoprost therapy by 19.9% in Group I, 20.5% in Group II, 16.6%
      in Group III, and 12.2% in Group IV. In Groups I and II, there was a significant
      positive correlation between the magnitude of IOP reduction induced by
      latanoprost and the IOP level before latanoprost therapy. The IOP level before
      latanoprost therapy is a contributing factor in the IOP-lowering efficacy of
      latanoprost. Latanoprost is more effective in lowering IOP than isopropyl
      unoprostone.

PMID- 11322635
TI  - Enhanced ocular hypotensive response to timolol in rabbits with prior
      dexamethasone treatment.
AB  - The purpose of this study was to determine glucocorticoid modulation of ocular
      pressure to timolol applied topically to rabbit eyes that were pretreated with
      dexamethasone. Rabbits were pretreated with five applications of topical 0.007%
      of dexamethasone (0.01% dexamethasone phosphate) or saline drops, administered at
      ten min intervals. The eyes were then treated with timolol maleate drops at
      concentrations of free base of 0.00007%, 0.0007%, 0.007% and 0.07%. An additional
      group of rabbits received dexamethasone pre-treatment only. Intraocular pressure
      was measured for the next four hr. Enhanced lowering of intraocular pressure was
      observed with dexamethasone pretreatment. Rabbits receiving the smaller dose of
      timolol had the least decrease in pressure. The most significant decreases in
      pressures occurred at 45 min after the administration of timolol with an average
      difference of 4.8 mm Hg between the timolol- and dexamethasone/timolol-treated
      eyes for the three largest concentrations of timolol. This synergism between
      glucocorticoids and beta-adrenergic blockers in lowering IOP may be potentially
      useful in the therapy of ocular hypertension and glaucoma.

PMID- 11322636
TI  - Functional pharmacological evidence for EP2 and EP4 prostanoid receptors in
      immortalized human trabecular meshwork and non-pigmented ciliary epithelial
      cells.
AB  - The aim of these studies was to characterize the molecular pharmacology of the
      prostanoid receptors positively coupled to stimulation of adenylyl cyclase
      activity in immortalized human trabecular meshwork (TM-3) cells and to compare
      these results with that of the receptors in immortalized human nonpigmented
      epithelial (NPE) cells. In general, the TM-3 and NPE cells showed a similar
      profile with respect to their responses to various prostaglandin (PG) receptor
      agonists. The rank order of potency (EC50; means +/- SEM) for these compounds in
      the TM-3 cells was: PGE2 (124 +/- 21 nM) > 13,14-dihydro-PGE1 (430 +/- 110 nM) =
      PGE1 (522 +/- 345 nM) > 11-deoxy-PGE1 (1063 +/- 118 nM) = 16,16-dimethyl-PGE2
      (1776 +/- 460 nM) = butaprost (1920 +/- 527 nM) >> PGD2 = PGI2 = PGF2alpha (n = 3
      - 12). While the agonist profile indicated the presence of EP2 receptors, the
      effects of the EP4 receptor antagonists suggested the additional expression of
      EP4 receptors in both of these cells. Thus, the EP4 receptor antagonist,
      AH23848B, at a concentration of 30 microM, caused a dextral shift in the PGE2
      concentration-response curves in both TM-3 and NPE cells coupled with a 20-28%
      decrease in the maximal response of PGE2, indicating apparent noncompetitive
      antagonism profiles. The antagonist potency of AH23848B in these cells was: Kb =
      38.4 +/- 14.8 microM and 23.5 +/- 4.5 microM; -log Kb = 4.7. The other EP4
      receptor antagonist, AH22921 (-log Kb = 4.1 - 4.7), was weaker than AH23848B.
      Taken together, these pharmacological studies have shown than TM-3 and NPE cells
      apparently contain functional EP2 and EP4 prostanoid receptors positively coupled
      to adenylyl cyclase.

PMID- 11322637
TI  - Calpain-induced light scattering in young rat lenses is enhanced by UV-B.
AB  - The purpose of this study is to determine if UV-B enhances light scattering after
      proteolysis of crystallins by calpains, and to determine if lens-specific calpain
      Lp82 is involved, along with m-calpain, in the mechanism of in vitro
      precipitation. Lens soluble proteins from young rats were hydrolyzed for 24 hr by
      endogenous lens calpains, and the proteins were further incubated for up to 7
      days with periodic irradiation by UV-B. Light scattering was measured daily at
      405 nm. SDS-PAGE and immunoblotting assessed proteolysis of crystallins,
      activation of calpains, and formation of high molecular weight aggregations.
      Appreciable light scattering occurred in lens soluble proteins after proteolysis
      of crystallins by m-calpain and Lp82. UV-B markedly enhanced this light
      scattering and the formation of higher molecular weight aggregates consisting of
      proteolyzed alpha- and beta- and intact gamma-crystallins. Calpain inhibitor E64
      and antioxidants DTE or GSH prevented the light scattering. These results show
      that calpain-induced light scattering is enhanced by the natural oxidant UV-B.
      Activation of Lp82, along with m-calpain, contributed to the light scattering.
      The linkage between proteolysis and oxidation is important because both oxidation
      and truncation of crystallins are found in aged human lenses, which are
      constantly exposed to UV irradiation.

PMID- 11322638
TI  - Effects of traditional Sino-Japanese herbal medicines on aqueous flare elevation
      after small-incision cataract surgery.
AB  - We evaluated prospectively the effects of traditional Sino-Japanese herbal
      medicines on elevation of aqueous flare. Fifty-four patients with age-related
      cataract undergoing phacoemulsification with intraocular lens implantation were
      studied. In the control group, 20 patients received no herbal medicine. In the
      treated groups, 14 patients were given Orengedoku- to (Huanglian-Jie-Du-Tang in
      Chinese) granules (7.5 g daily), 10 patients were given Kakkon-to (Ge-Gen-Tang in
      Chinese) granules (7.5 g daily), and 10 patients were given Sairei-to (Cai-Ling
      Tang in Chinese) granules (9.0 g daily), for 3 days before surgery, the day of
      surgery, and for 7 days after surgery. Aqueous flare was measured before and
      after surgery. The differences in preoperative flare intensities among the four
      groups were not significant. In the control group, the flare was 29.4 photon
      counts/msec on day 1, and then gradually decreased. The flare intensities on days
      1, 3, and 5 in the Orengedoku-to and Kakkon-to groups were significantly lower
      than in the control group. The flare intensities in the Sairei-to group were the
      same as those of the controls. Oral administration of Orengedoku-to and Kakkon-to
      decreased aqueous flare elevation after small-incision cataract surgery. Sairei
      to had no effect on the elevation.

PMID- 11322639
TI  - Inhibition of COX in ocular tissues: an in vitro model to identify selective COX
      2 inhibitors.
AB  - The aim of this work was to study the regulation of LPS-stimulated PGE 2
      synthesis by traditional NSAIDs (piroxicam and diclofenac) and a selective COX-2
      inhibitor (NS-398), in cultured bovine corneal endothelial cells and retinal
      pigmentary epithelial cells. The IC50 values of piroxicam and diclofenac were
      compared with IC50 values of NS-398, diclofenac, in both types of cells, showed
      higher potency than piroxicam. Diclofenac seemed to be a COX-2 inhibitor because
      its IC50 values were similar to the IC50 values of NS-398. We suggest that this
      in vitro cell assay system could be useful for identifying compounds that
      selectively inhibit COX-2 in ocular tissues.

PMID- 11322640
TI  - Respiratory and cardiovascular effects of WP-934 in guinea pigs.
AB  - WP-934 is a newly developed reversible thermo-setting in situ gelling ophthalmic
      solution containing timolol. We investigated the effects of WP-934 on the
      respiratory and cardiovascular systems in guinea pigs and compared them with
      those of the conventional ophthalmic solution of timolol. At 30 min after
      instillation of timolol 0.5%, the airway responsiveness to histamine was 4 times
      higher, and that to acetylcholine was 2.5 times higher, than that before
      instillation. At 30 min after instillation of WP-934 0.5%, in contrast, the
      increase in responsiveness to each drug was about half that seen with the
      conventional solution. Topical instillation of timolol 0.5% weakened the effects
      of salbutamol and aminophylline on bronchodilatation, while that of WP-934 0.5%
      had no effect on aminophylline-induced bronchodilatation and a weaker effect on
      salbutamol-induced bronchodilatation. Topical instillation of timolol 0.5% and WP
      934 0.5% failed to show a significant effect on blood pressure but caused a 10 to
      20% decrease in heart rate for at least 120 min after instillation. WP-934
      appears to have less respiratory adverse effects than timolol, mainly due to its
      longer retention on the ocular surface and a consequent decrease in systemic
      absorption.

PMID- 11322641
TI  - Bovine eye 1-Cys peroxiredoxin: expression in E. coli and antioxidant properties.
AB  - Peroxiredoxins constitute a molecular family of novel antioxidant proteins and
      are distributed broadly in non-mammalian and mammalian tissues, including the
      eye. In this study, a recombinant bovine eye 1-Cys peroxiredoxin (BRPrx) was
      expressed in Escherichia coli (E. coli). The recombinant protein protected
      glutamine synthetase from oxidative damage caused by a metal ion-catalyzed
      oxidation system (ascorbate/Fe3+/O2) in the presence of dithiothreitol as an
      electron donor. The protector activity of BRPrx is attributed to its peroxidase
      activity exhibited in the presence of dithiothreitol. Both hydrogen peroxide and
      short chain hydroperoxides are substrates for the protein. Glutathione could not
      support antioxidant properties of the recombinant protein. The antioxidant
      activity of BRPrx in the glutamine synthetase protection assay was as high as the
      activity of catalase and about one order of magnitude lower than that of selenium
      glutathione peroxidase. These results support the premise that Prx is an
      important component of the antioxidant defense system in eye tissues.

PMID- 11322642
TI  - In vitro effects of naloxone on T-lymphocyte-dependent antibacterial activity in
      hepatitis C virus (HCV) infected patients and in inflammatory bowel disease (IBD)
      patients.
AB  - Naloxone acts as an opioid antagonist, displacing opioid drugs from cellular
      receptors. Among opioid substances, beta-endorphins are able to bind to several
      cell receptors, even including those expressed by immune cells. In this respect,
      evidence has been provided that in the course of viral infections, as well as in
      patients with ulcerative colitis high levels of beta-endorphins are detectable.
      Here, peripheral blood lymphocytes (PBL) from 21 HCV infected patients and 14
      patients with IBD, respectively, were incubated with Naloxone and Naloxone + Ca2+
      in order to evaluate a putative modulation of PBL-mediated antibacterial
      activity. In fact, previous studies have demonstrated a reduction of this T-cell
      activity in HCV and IBD patients. In general terms, the above treatment led to a
      recovery of the depressed antibacterial activity. In some cases, increase in T
      lymphocyte function was obtained with Naloxone alone, while in other cases the
      combination Naloxone + Ca2+ gave rise to a restorative effect. Of note, in some
      instances, lymphocytes were unresponsive to pharmacological modulation. The
      overall results suggest that beta-endorphins may down modulate T-cell
      antibacterial response in HCV and in IBD patients by saturating peripheral
      receptors on immune cells. Therefore, it is likely that Naloxone and/or Naloxone
      + Ca2+ may displace opioid drugs, thus antagonizing their effects.

PMID- 11322643
TI  - Inhibitory effects of mast cell-mediated allergic reactions by cell cultured
      Siberian Ginseng.
AB  - The crude drug "Siberian Ginseng (SG)" has long been used in empirical Oriental
      medicine for the nonspecific enhancement of resistance in humans and animals. In
      this study, we investigated the effect of cell cultured SG by oral administration
      in mast cell-mediated allergic reactions. SG dose-dependently inhibited compound
      48/80-induced systemic allergy with doses of 10(-2) to 1 g/kg 1 h before oral
      administration. Of special note, SG inhibited systemic allergy with the dose of 1
      g/kg by 25%. SG (1 g/kg) also inhibited passive cutaneous allergic reaction by
      51%. SG dose-dependently inhibited histamine release from rat peritoneal mast
      cells. When SG (0.01 mg/ml) was added, the secretion of tumor necrosis factor
      alpha (TNF-alpha) and interleukin-6 in antidinitrophenyl (DNP) IgE antibody
      stimulated mast cells was inhibited 39.5% and 23.3%, respectively. In addition,
      SG inhibited anti-DNP IgE antibody-stimulated TNF-alpha protein expression in
      mast cells. Our studies provide evidence that SG may be beneficial in the
      treatment of various types of allergic diseases.

PMID- 11322645
TI  - Circulating cytokines and gastrin levels in asymptomatic subjects infected by
      Helicobacter pylori (H. pylori).
AB  - The pathophysiology of hypergastrinemia in H. pylori infection has been largely
      investigated and different reports clearly show that the infected antrum has a
      marked inflammatory response with a suggestive local production of cytokines.
      Notwithstanding, a few data are available on the circulating levels of cytokines
      and gastrin in the asymptomatic people carrying H. pylori infection. Thus, aim of
      the study was to evaluate circulating proinflammatory cytokines [Interleukin (IL)
      8, Interleukin (IL)-10, Interferon (IFN)-gamma, and Tumor Necrosis Factor (TNF)
      alpha] and gastrin levels in H. pylori positive asymptomatic subjects vs. H.
      pylori negative ones. To this end, thirty healthy volunteers with no digestive
      symptoms or systemic disease were enrolled and H. pylori infection was identified
      by a 13C-urea breath test. Plasma levels of gastrin were determined using the RIA
      kit whereas IL-8, TNF-alpha, IL-10, and IFN-gamma levels in serum were measured
      with a solid-phase ELISA. Fifteen infected people showed significantly higher
      gastrin and TNF-alpha levels than uninfected subjects. On the contrary, IL-8
      levels were significantly higher in the uninfected subjects than in H. pylori
      positive ones (P < 0.0422). IFN-gamma and IL-10 circulating levels were not
      affected by H. pylori presence, being not significantly different in the two
      groups.

PMID- 11322644
TI  - Effects of the green algae Chlorella vulgaris on the response of the host
      hematopoietic system to intraperitoneal ehrlich ascites tumor transplantation in
      mice.
AB  - Chlorella vulgaris extract (CVE) was examined for its effects on the Ehrlich
      ascites tumor-induced suppression in the numbers of bone marrow and spleen
      granulocyte-macrophage progenitor cells (CFU-GM) in mice. No effects on bone
      marrow and spleen CFU-GM, as compared to controls, were observed in normal mice
      given 50, 100 and 200 mg/kg CVE orally for 5 days. In tumor-bearing mice,
      myelosuppression concomitant with increased number of spleen CFU-GM were
      observed. The number of CFU-GM in the bone marrow was restored to control levels
      after the administration of CVE (50, 100 and 200 mg/kg) to tumor-bearing mice,
      and a slight reduction in spleen colony formation was observed in these animals.
      In addition, CVE significantly prolonged the survival of mice inoculated with the
      Ehrlich ascites tumor. These results suggest a protective antitumor effect of CVE
      which might be attributable, at least in part, to the stimulation of the
      production and, possibly, maturation of granulocytes and macrophages.

PMID- 11322646
TI  - Rhodiola sachalinesis induces the expression of inducible nitric oxide synthase
      gene by murine fetal hepatocytes (BNL CL.2).
AB  - We have examined the effect of the aqueous extract of Rhodiola sachalinensis root
      (RSE), a traditional herbal medicine, on nitric oxide (NO) synthesis in murine
      fetal hepatocytes (BNL CL.2) by measuring the stable end-product nitrite and the
      mRNA of inducible NO synthase (iNOS). Interferon-gamma (IFN-gamma) by itself
      failed to induce NO synthesis in BNL CL.2 cells. RSE also did not elicit NO
      synthesis at concentrations up to 1,000 microg/ml, but dose- and time-dependently
      induced NO synthesis in the presence of IFN-gamma in BNL CL.2 cells. Whereas RSE
      or IFN-gamma failed to induce detectable levels of iNOS mRNA, a combination of
      RSE and IFN-gamma markedly induced iNOS mRNA in BNL CL.2 cells. Thus, we found
      that RSE triggered IFN-gamma-primed BNL CL.2 cells to synthesize NO by inducing
      iNOS gene expression. The capability of RSE to induce NO synthesis might be
      related to the therapeutic efficacy of RSE on the liver diseases.

PMID- 11322647
TI  - Serum cytokine levels and antibody response to influenza vaccine in the elderly.
AB  - Cytokines play critical roles in regulating the antibody response to vaccines. We
      sought to understand the role of endogenous cytokines in the determination of
      antibody production in the elderly, a group of subjects known to have a lower
      response rate to vaccination. We found that in a healthy elderly group, only 52%
      of whom responded to the influenza vaccine, endogenous levels of interleukin 6
      (IL-6), IL-10 and gamma interferon (IFNgamma) did not differ statistically
      significantly between responders and non-responders (responders: n = 27, IL-6 =
      293 +/- 101 pg/ml, IL-10 = 882 +/- 240 pg/ml; nonresponders: n = 26, IL-6 = 223
      +/- 71 pg/ml, P = 0.57, IL-10 = 445 +/- 148 pg/ml, mean +/- SE, P = 0.14,
      respectively, and undetectable IFNgamma). Serum levels of these three cytokines
      were not changed significantly four weeks after vaccination (P < 0.05 for IL-6
      and P < 0.01 for IL-10). In addition, there were also no age-dependent
      differences in serum IL-6 and IL-10 levels.

PMID- 11322648
TI  - Modulatory effect of cyclosporin A on tert-butyl hydroperoxide-induced oxidative
      damage in hepatocytes.
AB  - In the present work, we followed an in vitro protective action of cyclosporin A
      (CsA) against tert-butyl hydroperoxide (t-BHP)-induced oxidative damage in
      hepatocytes. Various parameters (cell viability, cytosolic calcium level,
      rhodamine 123 accumulation as indicator of mitochondrial membrane potential and
      alanine-aminotransferase leakage from cells) were measured as an index of
      cytotoxicity. Tert-butyl hydroperoxide (1 mM) significantly increased cytosolic
      Ca2+ and affected mitochondrial membrane potential. Pretreatment with cyclosporin
      A (0.5 microM) reduced t-BHP-induced cytosolic Ca2+ increase and ALT (alanine
      aminotransferase) leakage, but had no protective effect on t-BHP-induced changes
      of mitochondrial membrane potential. Our data thus suggest that the mechanism of
      cytoprotection of CsA on the cytosolic Ca2+ changes and ALT leakage induced by t
      BHP, does not directly correlate with protection of t-BHP-induced changes of
      mitochondrial membrane potential.

PMID- 11322649
TI  - Gamma-interferon (IFN-gamma) augments apoptotic response to mistletoe lectin-II
      via upregulation of Fas/Fas L expression and caspase activation in human myeloid
      U937 cells.
AB  - Mistletoe lectin-II, a major composition of Korean mistletoe (Viscum album
      coloratum), is known as a potent apoptosis inducer. The previous research has
      demonstrated that Korean mistletoe lectin-II induces apoptosis via c-Jun N
      terminal kinase (JNK) activation in human myeloid U937 cells. The purpose of this
      research is to prove the synergistic action of mistletoe lectin-II and interferon
      gamma (IFN-gamma) in the apoptotic cytotoxicity of U937. When U937 cells were
      treated with mistletoe lectin-II after being differentiated by IFN-gamma, the
      proteolytic activity of caspase-3 and 9 was markedly elevated and that of caspase
      8 was prolonged for 18 hr. The activation of caspase-3-like protease requires the
      earlier cleavage of poly(ADP-ribose) polymerase(PARP). Caspase-1 was, however,
      not activated during the resting phase and nor in IFN-gamma-differentiated U937
      cells. Western blot analysis revealed that, in IFN-gamma-differentiated U937
      cells, the expression of Fas (CD95/APO-1) & Fas ligand(FasL) increases the
      apoptotic sensitivity against Mistletoe lectin-II. Fas (CD95/APO-1) & FasL were
      not significantly induced solely by mistletoe lectin-II. Furthermore the activity
      of JNK1 in U937 cells was also markedly increased with IFN-gamma-differentiation,
      compared to that of the control. These results suggest that the IFN-gamma
      differentiation of U937 cells increases the susceptibility to mistletoe lectin-II
      induced apoptosis.

PMID- 11322650
TI  - Different mechanisms in inhibition of rat macrophage nitric oxide synthase
      expression by FK 506 and cyclosporin A.
AB  - The modulatory effect of FK 506 and cyclosporin A (CsA) on the expression of
      inducible nitric oxide synthase (iNOS) in macrophages and mechanisms of their
      action were analysed. Isolated rat peritoneal macrophages were cultured for 12 or
      24 h with or without lipopolysaccharide (LPS) (5 microg/ml) and in the absence or
      presence of FK 506 or CsA (0.1 and 1 microg/ml). Total RNA from macrophages was
      isolated and the expression of the gene for iNOS was assessed by using RT-PCR.
      The concentration of NO2- in culture supernatants was taken as a measure of
      nitric oxide (NO) production. FK 506 (0.1 and 1 microg/ml) reduced the LPS
      induced increase of NO2- levels by 68% and 81%, respectively. CsA (0.1 and 1
      microg/ml) decreased levels of nitrites by 39% and 69%, respectively. The results
      obtained suggest that both immunosuppressive drugs exhibit dose-dependent
      inhibitory effect on NO production and that FK 506 is more potent agent than CsA,
      in this respect. FK 506 exhibits its inhibitory effect on a phosphatase at the
      transcriptional level in macrophages. iNOS expression down-regulation by CsA is
      occurred post-transcriptionally.

PMID- 11322651
TI  - Restoration of immunocyte functions by thymosin alpha1 in cyclophosphamide
      induced immunodeficient mice.
AB  - Thymosin alpha1 (Talpha1) is an oligopeptide hormone originally isolated from the
      thymus gland, and has been reported to have stimulating effects on the
      differentiation of T cells and NK cells. These immunostimulating properties have
      been considered to be useful for improving immune disorders associated with
      various diseases including cancer, AIDS and hepatitis. Here, we characterized
      immunostimulating properties of Talpha1 in experimental immunodeficiency of mice
      that was induced by the administration of cyclophosphamide (CY). Repeated
      injection of 30-300 microg/kg/day of Talpha1 after CY-treatment significantly
      accelerated the restoration of the reduced number of CD4+CD8+ T cells in the
      thymus. Talpha1 administration was effective in restoring the suppressed
      activities of helper T cells and cytotoxic T cells in CY-treated mice. Talpha1
      also had stimulating effects on reduced activity of lymphokine-activated killer
      cells in CY-treated mice. These results indicate that Talpha1 is stimulatory for
      both humoral and cellular immune responses, thus providing the immunological
      basis for the clinical benefit of this compound.

PMID- 11322652
TI  - Podophyllotoxin lignans enhance IL-1beta but suppress TNF-alpha mRNA expression
      in LPS-treated monocytes.
AB  - There exists a growing body of research which indicates that antimitotics such as
      taxol and colchicine influence cytokine gene expression. In the present study we
      examined the effect of podophyllotoxin and six analogs on nuclear factor kappa B
      (NF-kappa B) activation, and on interleukin-1 beta (IL-1beta) and tumor necrosis
      factor alpha (TNF-alpha) mRNA expression in human THP-1 monocytes. All compounds
      were inactive between 0.001microM and 10microM when tested alone. However,
      podophyllotoxin (0.1 microM) enhanced LPS-induced NF-kappa B activation and IL
      1beta mRNA expression between 2 and 3-fold. In contrast, LPS-induced TNF-alpha
      mRNA expression was decreased between 3 and 6-fold. Comparable results were also
      observed with the three analogs acetylpodophyllotoxin, 4'-demethylpodophyllotoxin
      and alpha-peltatin. The remaining three analogs (podophyllotoxin-4-O-glucoside,
      beta-peltatin-beta-D-glucopyransoide and 1,2,3,4-dehydrodesoxypodophyllotoxin)
      were inactive. Clearly certain structural features such as the presence of a
      glycosidic group or ring aromatization results in loss of biological activity.
      Interestingly, the analogs that were inactive in our assays have also been
      previously shown to lack affinity for tubulin binding. These results suggest that
      during the initial hours of exposure to podophyllotoxin or specific analogs these
      compounds do not act as independent stimulants of human monocyte activation, but
      can selectively enhance or suppress LPS-induced cytokine gene expression.

PMID- 11322653
TI  - Inhibitory effect of tumor necrosis factor-alpha secretion from rat astrocytes by
      Chilbokeum.
AB  - Substance P (SP) can stimulate secretion of tumor necrosis factor-alpha (TNF
      alpha) from astrocytes stimulated with lipopolysaccharide (LPS). In this study,
      we have examined whether an aqueous extract of Chilbokeum inhibits secretion of
      TNF-alpha from primary cultures of rat astrocytes. Chilbokeum (10 microg/ml)
      significantly inhibited the TNF-alpha secretion by astrocytes stimulated with LPS
      and SP. Interleukin-1 (IL-1) has been shown to elevate TNF-alpha secretion from
      LPS-stimulated astrocytes while having no effect on astrocytes in the absence of
      LPS. We therefore examined whether IL-1 mediated inhibition of TNF-alpha
      secretion from primary astrocytes by Chilbokeum. Treatment of Chilbokeum (10 and
      100 microg/ml) to astrocytes stimulated with both LPS and SP decreased IL-1
      secretion significantly. Moreover, the secretion of TNF-alpha by LPS and SP in
      astrocytes was progressively inhibited with increasing amount of IL-1
      neutralizing antibody. Our results suggest that Chilbokeum may inhibit TNF-alpha
      secretion by inhibiting IL-1 secretion and that Chilbokeum has an
      antiinflammatory activity in the central nervous system.

PMID- 11322654
TI  - A linkage disequilibrium at the candidate gene locus for 16q-linked autosomal
      dominant cerebellar ataxia type III in Japan.
AB  - We previously mapped the gene responsible for autosomal dominant cerebellar
      ataxia (ADCA) type III to a 10.9-cM interval between D16S3089 and D16S515 on
      chromosome 16q. This region, however, was identical to the candidate locus of
      spinocerebellar ataxia type 4 (SCA4). In this study, we extended our research to
      refine the gene locus of the disease by applying linkage disequilibrium with 20
      microsatellite DNA markers. With 9 markers flanked by D16S3031 and D16S3107, we
      found that the affected individuals in six families had a common haplotype on
      their disease chromosomes. Furthermore, linkage disequilibrium was demonstrated
      with 5 informative markers: D16S3019 (P = 0.013), D16S3067 (P = 0.008), D16S3141
      (P = 0.011), D16S496 (P = 0.032), and D16S3107 (P = 0.000). These results
      indicate that the disease could have originated from a common ancestor harboring
      a mutation within a less than 3-cM region between D16S3043 and D16S3095. The
      founder alleles were also observed in other patients with ADCA type III unrelated
      to the six families.

PMID- 11322655
TI  - Effects of hepatic lipase gene promoter nucleotide variations on serum HDL
      cholesterol concentration in the general Japanese population.
AB  - Genetic factors may play a major role in determining serum high-density
      lipoprotein (HDL) cholesterol (HDL-C) levels in the general population.
      Cholesteryl ester transfer protein (CETP) is a strong genetic factor as a
      determinant of HDL-C levels in Japanese, whereas hepatic lipase (HL) plays a
      predominant role in Caucasian populations. We investigated the effects of HL gene
      promoter polymorphisms on HDL-C levels in a general population of Japanese men (n
      = 299). An HL promoter polymorphism of -514C/T explained a considerable variance
      of HDL-C (2.9%), as compared with CETP mutations of D442G and IVS14 + 1G > A
      (3.6% and 1.9%). HL promoter variation of the -514C/C genotype, reported to have
      high HL activity, had significant effects on decreasing HDL-C levels (-3.8mg/dl),
      but -514T allele carriers had a weak effect on increasing HDL-C levels. The
      frequency of the -514T allele was three times higher (0.50) in the Japanese than
      in Caucasian populations (0.15-0.19). Thus, the higher frequency of the HL -514T
      allele, along with CETP gene mutations, could explain about 9% of phenotypic
      variability of HDL-C. These genetic attributes may be among the many factors that
      contribute to the relatively higher serum HDL-C levels in Japanese subjects.

PMID- 11322656
TI  - Insertion and deletion mutations in the dinucleotide repeat region of the Norrie
      disease gene in patients with advanced retinopathy of prematurity.
AB  - Retinopathy of prematurity (ROP) is a leading cause of blindness in premature
      children. It is a multifactorial disorder which causes fibrovascular tissue
      changes that affect the retina in low birth-weight and short gestational age
      infants. To determine the prevalence of Norrie disease (ND) gene mutations,
      clinical examination and molecular genetic analyses were performed in 100 pre
      term babies of different ethnic backgrounds who developed advanced ROP. The
      leukocyte DNA was extracted, amplified by the polymerase chain reaction (PCR),
      and analyzed by single-strand conformation polymorphism (SSCP), G/T and C/A
      scanning, and by DNA sequencing. All three exons, including splice sites and the
      3'-untranslated region, were screened. Of the 100 patients analyzed, 2 patients
      with advanced ROP showed a mobility shift in the DNA. In 1 patient, this mobility
      shift was caused by the insertion of an additional 12-bp CT repeat in exon 1, and
      in the second patient, there was a 14-bp deletion in the same exon of the ND
      gene, as evidenced by direct sequencing of the amplified products. Similar
      analyses of exons 2 and 3 and the 3'-untranslated region failed to detect
      additional mutations in the gene. None of the 130 normal, unrelated controls
      revealed similar changes. Taking into account the above results, as well as those
      of other studies, it appears that the ND gene mutations can account for 3% of
      cases of advanced ROP. Although the ND gene is not frequently involved in
      advanced ROP, the present large-scale study further supports the hypothesis that
      genetic influences may play an important role in the development of severe ROP in
      some premature infants.

PMID- 11322657
TI  - The c-Jun NH2-terminal kinase3 (JNK3) gene: genomic structure, chromosomal
      assignment, and loss of expression in brain tumors.
AB  - By examining 19 human cell lines derived from brain tumors for altered expression
      of expressed sequence tags (ESTs) in chromosomal band 4q21-22, we detected loss
      of expression, in 10 cell lines, of two sequences, WI6336 and WI7913. Both
      corresponded to the c-Jun NH2-terminal kinase (JNK) 3. In the present study,
      genomic cloning revealed that the JNK3 gene consists of 14 exons interrupted by
      13 introns; its transcription-initiation site is within exon 3 and the
      termination codon lies in exon 14. Fluorescence in situ hybridization (FISH) and
      radiation-hybrid mapping confirmed the gene to 4q21-22. Together with prior
      evidence that, in JNK3-deficient mice, the JNK3 signaling pathway mediates
      apoptosis in central nervous tissue, our results suggest that loss of expression
      of the JNK3 gene may play an important role in the development of brain tumors in
      humans.

PMID- 11322658
TI  - The C825T polymorphism in the G-protein beta3 subunit gene and diabetic
      complications in IDDM patients.
AB  - Complications of insulin-dependent diabetes mellitus (IDDM) are a major cause of
      morbidity and mortality; however, the mechanisms of their development are still
      to be elucidated. Genetic susceptibility contributes to the pathogenesis of
      nephropathy in IDDM. Enhanced G-protein activation, a cellular phenotype observed
      in cultured cells from patients with essential hypertension, was recently
      documented in IDDM subjects with nephropathy. A C825T polymorphism was recently
      described in GNB3, the gene encoding the beta 3 subunit of heterotrimeric G
      proteins. This genetic variant has been associated with enhanced G-protein
      activation. The 825T allele was observed more frequently in a group with
      essential hypertension. We analyzed the role of the C825T polymorphism in the
      predisposition to diabetic complications in IDDM. In this study, we investigated
      the frequency of this polymorphism in a large case-control study and found no
      association of the 825T allele with diabetic nephropathy, retinopathy, and
      neuropathy.

PMID- 11322659
TI  - Fabry disease: twenty novel alpha-galactosidase A mutations causing the classical
      phenotype.
AB  - Fabry disease, an X-linked inborn error of glycosphingolipid catabolism, results
      from the deficient activity of the lysosomal exoglycohydrolase, alpha
      galactosidase A (EC 3.2.1.22; alpha-Gal A). The nature of the molecular lesions
      in the alpha-Gal A gene in 40 unrelated families with the classical phenotype
      (absent alpha-Gal A activity) was determined in order to provide precise
      heterozygote detection and prenatal diagnosis, and to explore possible
      genotype/phenotype correlations. Genomic DNA was isolated from unrelated affected
      males, and the entire alpha-Gal A coding region and flanking intronic sequences
      were analyzed by polymerase chain reaction (PCR) amplification and automated
      sequencing. Twenty new mutations were identified: M51K, D92N, D136H, F169S,
      C172F, L191Q, S247P, Q250X, P259R, G261D, T282N, R301P, W349X, T410K, 124delAT,
      842delTAA, 1033delTC, 82insG, 893insG, and 903insG. In the remaining 20 unrelated
      Fabry families, 17 previously reported mutations were detected. These studies
      further define the heterogeneity of mutations in the alpha-Gal A gene causing the
      classic Fabry disease phenotype, and permit precise heterozygote detection and
      prenatal diagnosis.

PMID- 11322660
TI  - Comparative analysis of HLA restriction and cytokine production in hepatitis B
      surface antigen-specific T cells from low- and high-antibody responders in
      vaccinated humans.
AB  - It is well known that individuals with low, or lack of, antibody production in
      response to hepatitis B surface antigen (HBsAg) exist in the human population. We
      have previously reported that HLA class I and class II genes are both involved in
      antibody production to HBsAg, and that specific alleles of HLA are associated
      with low and high antibody production. To elucidate further the mechanisms by
      which the diversity of antibody production to HBsAg is generated in humans, a
      total of 146 T-cell clones specific for HBsAg were produced from six healthy
      vaccinees (three low- and three high-antibody responders) and were examined for
      cytokine production and HLA restriction. It was found that the majority of the T
      cell clones from the low-antibody responders were Th1- or Th0-like T cells (62%
      or 19%, respectively), whereas the majority of T-cell clones from the high
      antibody responders were Th2-like T cells (77%), suggesting predominant expansion
      of Th1/Th0- and Th2-like T cells specific for HBsAg in the low- and high-antibody
      responders, respectively. This is the first evidence that the diversity of the
      response to HBsAg in humans is controlled by the activation of functionally
      distinct CD4+ T-cell subsets, i.e., Th0, Th1, or Th2 T cells.

PMID- 11322661
TI  - Establishment of an optimized set of 406 microsatellite markers covering the
      whole genome for the Japanese population.
AB  - Microsatellites, an essential tool for genetic linkage analyses, are selected in
      genetic studies on the basis of both informativeness and their positions with
      respect to one another on the genetic map. In order to establish a microsatellite
      marker set useful for linkage studies in the Japanese population, we first
      genotyped 64 unrelated Japanese subjects, using 400 microsatellite markers from a
      commercially available set (ABI PRISM Linkage Mapping Set-MD10) and then
      determined the allelic frequencies and heterozygosities for these marker loci in
      the population. In order to optimize the set, we replaced 41 markers having a
      heterozygosity lower than 0.6 with as many informative markers in the
      corresponding loci, and newly added six markers in the set to minimize the
      several gaps found at intervals of over 20 cM. We finally established a set
      comprising 406 microsatellites with average intervals of 9cM (maximum, 17 cM) and
      minimum heterozygosities of over 0.6 (mean, 0.76). All data generated in this
      study, including the specific polymerase chain reaction (PCR) primer sequences of
      the newly added markers, are freely available to all researchers at our web site.
      The genetic tool established here should facilitate genetic linkage studies of
      various hereditary diseases, especially in the Japanese.

PMID- 11322662
TI  - Mitochondrial DNA polymorphisms in Yunnan nationalities in China.
AB  - Nucleotide sequences of the D-loop region of human mitochondrial DNA from four
      Yunnan nationalities, Dai, Wa, Lahu, and Tibetan, were analyzed. Based on a
      comparison of 563-bp sequences in 99 people, 66 different sequence types were
      observed. Of these, 64 were unique to their respective populations, whereas only
      2 types were shared between the Lahu and Wa nationalities. The D-loop sequence
      variation and phylogenetic analysis suggested that the 99 mtDNA lineages were
      classified into eight clusters in the phylogenetic tree. All lineages that had a
      9-bp deletion in the COII/tRNALYs intergenic region appeared in one cluster in
      the D-loop tree, suggesting a single event of the deletion in the Yunnan
      nationalities studied. Genetic distances, based on net nucleotide diversities
      between populations including Han Chinese and mainland Japanese, revealed that
      the Dai, Wa, Lahu, and Han Chinese are closely related to each other, while
      Tibetan and mainland Japanese formed a single cluster. The bootstrap probability
      of separation between the Dai-Wa-Lahu-Chinese clade and the Tibetan-Japanese
      clade was 99%, indicating that there are at least two different origins among
      minority groups in Yunnan province. Although the genetic distance between Tibetan
      and Japanese within the clade is rather long, the results may shed light on the
      origins of mainland Japanese.

PMID- 11322663
TI  - Loci on murine chromosomes 7 and 13 that modify the phenotype of the NOA mouse,
      an animal model of atopic dermatitis.
AB  - The NOA (Naruto Research Institute Otsuka Atrichia) mouse is an animal model of
      allergic or atopic dermatitis, a condition characterized by ulcerative skin
      lesions with accumulation of mast cells and increased serum IgE. We reported
      earlier that a major gene responsible for dermatitis in the NOA mouse lay in the
      middle of chromosome 14, and that the incidence of disease clearly differed
      according to parental strain; the mode of inheritance was autosomal recessive
      with incomplete penetrance. In the study reported here, we searched for genes
      that might modify the NOA phenotype, and we identified two candidate loci that
      appeared to contain genes capable of modifying atopic or allergic dermatitis, one
      in the middle of chromosome 7 (chi2 = 14.66; P = 0.00013 for D7Mit62) and the
      other in the telomeric region of chromosome 13 (chi2 = 15.352; P = 0.000089 for
      D13Mit147). These loci correspond to regions of synteny in human chromosomes
      where linkages to asthma, atopy, or related phenotypes, such as serum IgE levels,
      have been documented.

PMID- 11322664
TI  - Catalog of 320 single nucleotide polymorphisms (SNPs) in 20 quinone
      oxidoreductase and sulfotransferase genes.
AB  - Single nucleotide polymorphisms (SNPs) in genes encoding drug-metabolizing
      enzymes, transporters, receptors, and other drug targets have been widely
      implicated as contributors to differences among individuals as regards the
      efficacy and toxicity of many medications, as well as the susceptibility to
      complex diseases. By combining the polymerase chain reaction (PCR) technique with
      direct sequencing, we screened genomic DNAs from 48 Japanese volunteers for SNPs
      in genes encoding three quinone oxidoreductases (NQO1, NQO2, and PIG3) and 17
      sulfotransferases (SULT1A1, SULT1A2, SULT1A3, SULT1C1, SULT1C2, SULT2A1, SULT2B1,
      ST1B2, TPST1, TPST2, SULTX3, STE, CST, HNK-1 ST, CHST2, CHST4, and CHST5). In
      all, we identified 320 SNPs from these 20 loci: 22 within coding elements, 21 in
      5' flanking regions, 10 in 5' untranslated regions, 223 in introns, 19 in 3'
      untranslated regions, and 25 in 3' flanking regions. The ratio of transitions to
      transversions was approximately 2.3 to 1. Of the 22 coding SNPs, 6 were
      nonsynonymous substitutions that resulted in amino-acid substitutions. The high
      density SNP maps we constructed from this data for each of the quinone
      oxidoreductases and sulfotransferases examined here should provide useful
      information for investigations designed to detect association(s) between genetic
      variations and common diseases or responsiveness to drug therapy.

PMID- 11322665
TI  - Evaluation of RP2 and RP3 genes in an X-linked RP family manifesting loss of
      central vision and preserved peripheral function.
AB  - X-Linked retinitis pigmentosa is a most severe and heterogeneous disorder of the
      retina. Recently, genes (RP2 and RPGR) from two X-linked loci have been
      positionally cloned and mutations have been identified in many families. To
      further evaluate allelic and non-allelic heterogeneity and the genotype-
      phenotype relationships, and to determine the prevalence of mutations in the
      gene, we have analyzed one previously unreported X-linked retinitis pigmentosa
      family, using a combination of haplotype analysis and DNA sequencing. Our
      extensive analysis of the RP2 gene failed to detect any disease--causing or
      polymorphic mutations. In the case of the RP3 gene, the alleles of the
      dinucleotide repeat marker did not segregate with the disease. Although we cannot
      completely exclude the possibility of the RP2 and RP3 genes as candidate genes,
      the above results suggest that structural and functional changes associated with
      the RP2 gene are not responsible for the phenotype in the family analyzed.
      Further identification of the X-linked genes may facilitate the elucidation of
      the molecular basis of the disorder in the family analyzed.

PMID- 11322666
TI  - Treating depression in old age: the reasons to be positive.
AB  - Depression affects 10-15% of people over 65 living at home in the United Kingdom.
      It is the commonest and the most reversible mental health problem in old age.
      Depression is associated with physical illness and disability, life events,
      social isolation and loneliness. Depression in old age carries an increased risk
      of suicide and natural mortality. Recognition and simple intervention can reduce
      morbidity, demand on health and social services and the cost of community care.
      Despite a favourable response to treatment, depression remains largely undetected
      and untreated.

PMID- 11322667
TI  - Development and implementation of resuscitation guidelines: a personal
      experience.
AB  - OBJECTIVES: to develop and implement guidelines on the appropriate use of
      cardiopulmonary resuscitation, which would ensure patient involvement in decision
      making about cardiopulmonary resuscitation whenever possible but without offering
      illusory choices where resuscitation was unlikely to succeed. DESIGN:
      quantitative guidelines were developed after a review of the literature on
      survival after cardiopulmonary resuscitation. Patients were classified according
      to their estimated likelihood of survival to discharge after resuscitation: < 1%,
      group A; 1-10%, group B; and > 10%, group C. Qualitative guidelines were
      developed after consideration of the legal and ethical principles of
      cardiopulmonary resuscitation. It was decided to inform competent patients in
      group A that cardiopulmonary resuscitation would be inappropriate, and to seek
      the preferences of competent patients in group B. The operation of the guidelines
      was examined in patients aged 65 years or more admitted under a single consultant
      in an acute community hospital. RESULTS: 147 patients were studied: 39 in group
      A, 26 in group B and 82 in group C. Of 36 patients in groups A and B judged
      competent, cardiopulmonary resuscitation discussions were only undertaken in 17,
      usually because acute distress or anxiety precluded effective communication. Of
      the 23 patients or family members from whom cardiopulmonary resuscitation
      preferences were sought, four opted for full cardiopulmonary resuscitation and
      six for limited cardiopulmonary resuscitation (usually witnessed-arrest only and
      no ventilation). CONCLUSION: it is difficult to involve acutely ill elderly
      patients in cardiopulmonary resuscitation decision-making. Limited
      cardiopulmonary resuscitation is a useful option for patients, relatives and
      doctors.

PMID- 11322668
TI  - Pictorial outcome measures for the hospital care of older patients--a suggested
      toolkit.
AB  - OBJECTIVE: to propose three pictorial methods of presenting hospital outcome
      data, suitable for use in older patients entering medical specialties (including
      rehabilitation). PATIENTS: 224 patients (mean age 80.6 years, 56% female, 75%
      emergencies) admitted to a department of medicine for the elderly. PRESENTATIONAL
      TECHNIQUES: the methods we propose for the presentation of outcome data are (i)
      place of discharge, using a two-dimensional diagram; (ii) 'survival' analyses,
      but using discharge from hospital rather than death as the endpoint; and (iii)
      'phase diagrams', a novel method of charting the progress of a cohort of
      patients. To illustrate these methods, the relationship between admission case
      mix (with patients put into tertiles on the basis of their Barthel index score)
      and outcome is shown graphically. RESULT: each of the three techniques has
      different relative strengths, but their pictorial nature allows for rapid
      interpretation of data, showing, for example, the marked influence of case-mix.
      Separate analyses of subgroups of patients (such as those who die in hospital and
      those who survive) are also readily attainable by the three methods. CONCLUSIONS:
      the three methods of presenting outcome should be of benefit in comparing the
      performance of different units, particularly when case-mix is taken into account.
      The pictorial methods are complementary both to more conventional patient-based
      methods (mean duration of stay, median duration of stay, percentile duration of
      stay, regression analyses etc) and to modelling techniques using 'census' data
      from large numbers of patients.

PMID- 11322669
TI  - Falls and Parkinson's disease.

PMID- 11322670
TI  - A pharmacy discharge plan for hospitalized elderly patients--a randomized
      controlled trial.
AB  - OBJECTIVES: to investigate the effectiveness of a pharmacy discharge plan in
      elderly hospitalized patients. DESIGN: randomized controlled trial. SUBJECTS AND
      SETTINGS: we randomized patients aged 75 years and older on four or more
      medicines who had been discharged from three acute general and one long-stay
      hospital to a pharmacy intervention or usual care. INTERVENTIONS: the hospital
      pharmacist developed discharge plans which gave details of medication and support
      required by the patient. A copy was given to the patient and to all relevant
      professionals and carers. This was followed by a domiciliary assessment by a
      community pharmacist. In the control group, patients were discharged from
      hospital following standard procedures that included a discharge letter to the
      general practitioner listing current medications. OUTCOMES: the primary outcome
      was re-admission to hospital within 6 months. Secondary outcomes included the
      number of deaths, attendance at hospital outpatient clinics and general practice
      and proportion of days in hospital over the follow-up period, together with
      patients' general well-being, satisfaction with the service and knowledge of and
      adherence to prescribed medication. RESULTS: we recruited 362 patients, of whom
      181 were randomized to each group. We collected hospital and general practice
      data on at least 91 and 72% of patients respectively at each follow-up point and
      interviewed between 43 and 90% of the study subjects. There were no significant
      differences between the groups in the proportion of patients re-admitted to
      hospital between baseline and 3 months or 3 and 6 months. There were no
      significant differences in any of the secondary outcomes. CONCLUSIONS: we found
      no evidence to suggest that the co-ordinated hospital and community pharmacy care
      discharge plans in elderly patients in this study influence outcomes.

PMID- 11322671
TI  - Relationship between age and plasma esterases.
AB  - INTRODUCTION: the older population is the most medicated. Despite high drug
      usage, older people are generally excluded from the research underpinning new
      drug development. This means that drugs are prescribed to older people with very
      little understanding of how they are likely to metabolize them. More research is
      needed to investigate the possible effects of ageing on the biotransformation of
      drugs. We therefore undertook a cross-sectional study examining the effect of age
      on the activities of benzoylcholinesterase, butyrylcholinesterase,
      acetylcholinesterase and aspirin esterase. METHODS: we measured the activities of
      benzoylcholinesterase and butyrylcholinesterase in 70 healthy volunteers aged 18
      85 years. We measured the activities of acetylcholinesterase and aspirin esterase
      in 43 healthy volunteers aged 18-85 years. We determined plasma activities of
      benzoylcholinesterase, butyrylcholinesterase, acetylcholinesterase and aspirin
      esterase spectrophotometrically. RESULTS: we found no correlation between the
      activities of any of the enzymes measured and advancing age. CONCLUSION: age per
      se is not associated with reductions in the activities of esterase enzymes.

PMID- 11322672
TI  - A community-dwelling sample of people with Parkinson's disease: characteristics
      of fallers and non-fallers.
AB  - BACKGROUND: people with Parkinson's disease often fall. OBJECTIVES: to report the
      frequency of falls and characteristics of fallers and non-fallers in a community
      based sample of people with Parkinson's disease. METHOD: we administered a
      battery of standardized tests in the home and the laboratory. RESULTS: we
      recruited 63 people with Parkinson's disease through general practices. Forty
      (64%, 95% confidence interval 51-74%) had fallen in the previous 12 months. Many
      factors associated with falling in the general population were associated with
      Parkinson's disease fallers (e.g. use of multiple medication and greater physical
      disability). Fallers were more likely to be depressed and anxious than non
      fallers. Condition-specific factors associated with falling included greater
      disease severity (although there were exceptions) and more marked response to
      levodopa treatment, including more dyskinesia and on-off phenomena. Fallers took
      more steps to complete a test of mobility. They also had a shorter functional
      reach and greater postural sway whilst completing a dual task than non-fallers.
      CONCLUSION: this community-based study confirms the high risk of falling in
      Parkinson's disease. Our results suggest that disease-specific factors contribute
      to the increased risk and that there is scope for specific therapeutic
      interventions.

PMID- 11322673
TI  - Mental capacity and medical decisions.

PMID- 11322674
TI  - Health and ill-health in the older population in England and Wales. The Medical
      Research Council Cognitive Function and Ageing Study (MRC CFAS).
AB  - OBJECTIVE: to provide a profile of disorders and disabilities in the older
      population. DESIGN: the MRC CFAS drew population samples of people aged 64 years
      and over from Family Health Service Authority lists at five sites and asked
      participants about sociodemographic variables, physical and cognitive health and
      activities of daily living, We calculated the prevalence of co-morbidity from the
      number of different types of complaint or disability (physical, functional and
      cognitive), and calculated healthy life expectancies in each of these co-morbid
      states. SETTING: three urban (Newcastle, Nottingham and Oxford) and two rural
      sites (Cambridgeshire and Gwynedd). RESULTS: the prevalence of morbidity is low
      at the youngest ages, as is co-morbidity. Women have consistently greater
      morbidity than men. Morbidity increases sharply with age, with a more dramatic
      rise in women. Life expectancy without any morbidity is short at all ages over
      64, with the number of years expected with two or more areas affected virtually
      constant up to 90 years. As a proportion of remaining life expectancy, the period
      of time spent with two or more areas affected rises by the age of 90 to 30% in
      men and 60% in women. CONCLUSIONS: preventive programmes for the older population
      should take into account the large differences between the young old, the middle
      old and the old old. Our study provides a baseline against which to compare
      future changes in health in older populations, as well as benchmark expectancies
      for the UK population.

PMID- 11322675
TI  - Measuring the quality of urinary continence care in long-term care facilities: an
      analysis of outcome indicators.
AB  - BACKGROUND: the National Centre for Health Outcomes Development has produced
      outcome indicators for the assessment of quality of care in the management of
      urinary incontinence. Three measures relate to the management of older people in
      long-term care: the prevalence of incontinence, the use of indwelling catheters
      and clinical assessment rates. OBJECTIVE: to evaluate the recommended outcome
      measures in clinical practice. METHOD: participating centres included residential
      homes, nursing homes and long-stay wards. We sent a structured questionnaire to
      each centre for qualitative assessment of the acceptability of the outcome
      indicators. We analysed data collected by nurses and other staff who used the
      urinary incontinence section of the Royal College of Physicians Continuous
      Assessment Review and Evaluation scheme audit tool for long-term care. RESULTS:
      there were 1125 residents in 17 residential homes, 14 nursing homes and five long
      stay wards. The overall prevalence of urinary incontinence was 34% in residential
      homes (range 2-86%), 70% in nursing homes (38-100%) and 71% in long-stay wards (4
      97%). Catheterization rates were 5% in residential homes (0-20%), 10% in nursing
      homes (0-44%) and 6% in long-stay wards (0-20%). Rates of full clinical
      assessment were 48, 24 and 36% respectively. CONCLUSION: there is great
      variability in these outcome measures within and between settings. Interpretation
      of outcome results requires more precise details on case-mix and the definition
      of outcome measures. Individual units found the audit tool helpful, but we advise
      caution with interpretation of outcomes between units.

PMID- 11322676
TI  - The development and use of a method to compare the costs of acute stroke across
      Europe.
AB  - BACKGROUND: there is a need for more information on the costs of different ways
      of managing stroke. Methods to compare the costs of stroke care in different
      countries have not been previously developed. OBJECTIVE: to develop and use a
      method to compare the costs of acute stroke care across Europe. SETTING: acute
      hospitals in 13 different European centres. SUBJECTS AND METHODS: we included in
      the study stroke patients hospitalized during 1996-7 at 13 centres across Europe
      (n=2072). We recorded the duration of acute hospital stay and use of
      investigations. Mean costs for each centre were predicted using linear regression
      analysis to adjust for case-mix differences. RESULTS: the average acute hospital
      stay ranged from 9 days (Spain) to 35 days (UK; P < 0.001). The predicted mean
      cost of treating conscious, continent men aged > 74 ranged from $220 (95%
      confidence interval 191-254) in Latvia to $5164 (4294-6191) in Austria.
      CONCLUSIONS: differences in the acute costs of stroke exist across Europe because
      of differences in clinical practice and unit costs. This methodology will be used
      to capture the costs incurred by a broad range of care providers. These estimates
      will then be suitable for using in cost-effectiveness analysis.

PMID- 11322677
TI  - Management of older patients with hypertension in primary care: improvement on
      the rule of halves.
AB  - OBJECTIVES: the benefits of treatment of hypertension in older people are well
      established but implementation of this knowledge may be sub-optimal. We have
      determined recent primary care management of older people with hypertension.
      METHODS: we examined health records (n = 6986) of a 1 in 7 sample of patients
      aged 65-80 years from a random sample of practices (n = 51) in the former
      Northern Region of the UK, stratified by health authority, for the previous 6
      years. We recorded documented risk factors, diagnosis of hypertension, three most
      recent blood pressure readings, current drug therapy and previous blood pressure
      lowering therapy, and presence of coexistent pathology. RESULTS: blood pressure
      was defined as hypertensive (> or = 160/> or = 90 mmHg; one or both values above
      these limits), normotensive or undetermined using a validated algorithm. In 30%
      of patients, blood pressure status was undetermined. Thirty-five percent of
      subjects were found to be hypertensive. Of these, 70% were receiving
      antihypertensive treatment but only 30% of treated patients had controlled (< 150
      and 90 mmHg) and 13% well controlled (< 140 and 85 mmHg) blood pressure. In all,
      14% of older hypertensive patients were detected, treated and had their
      hypertension controlled. There were significant differences between practices in
      the proportion of hypertensive patients treated (P < 0.001) and in the proportion
      of hypertensive patients whose blood pressure was controlled (P < 0.01).
      CONCLUSIONS: treatment of hypertension in older people in primary care has
      improved in terms of detection and treatment but in only one-third of patients is
      high blood pressure controlled. There remain important opportunities for
      prevention of stroke and myocardial infarction in this age group through
      achieving improved blood pressure control.

PMID- 11322678
TI  - Practical implementation of an exercise-based falls prevention programme.
AB  - Muscle weakness and impaired balance are risk factors underlying many falls and
      fall injuries experienced by older people. Fall prevention strategies have
      included exercise programmes that lower the risk of falling by improving strength
      and balance. We have developed an individually tailored, home-based, strength and
      balance retraining programme, which has proven successful in reducing falls and
      moderate fall injuries in people aged 80 years and older. Here we describe a
      simple assessment of strength and balance and the content and delivery of a falls
      prevention exercise programme.

PMID- 11322679
TI  - The grandmothers' disease--the impact of AIDS on Africa's older women.

PMID- 11322680
TI  - Protein-energy oral supplementation in malnourished nursing-home residents.

PMID- 11322681
TI  - Clinical measures: reliable or not?

PMID- 11322682
TI  - Clinical measures: reliable or not?

PMID- 11322683
TI  - Treating acquired haemophilia: an ethical conundrum.

PMID- 11322684
TI  - Osteoporosis and the role of vitamin D and calcium.

PMID- 11322685
TI  - Heparin thromboprophylaxis after acute stroke.

PMID- 11322686
TI  - Major aphthous ulcers induced by nicorandil.

PMID- 11322687
TI  - An eosinophilic pneumonia in a 93-year-old man.

PMID- 11322688
TI  - Diltiazem for nocturnal leg cramps.

PMID- 11322689
TI  - Non-bacterial thrombotic endocarditis and cancer.

PMID- 11322690
TI  - Hyponatraemia associated with the use of a selective serotonin-reuptake inhibitor
      in an older patient.

PMID- 11322691
TI  - A Chinese fermented soybean food.
AB  - Sufu or furu is a fermented soybean product originating in China. It is a cheese
      like product with a spreadable creamy consistency and a pronounced flavour. Sufu
      is a popular side dish consumed mainly with breakfast rice or steamed bread. It
      has a long history and written records date back to the Wei Dynasty (220-265 AD).
      Sufu is made by fungal solid state fermentation of tofu (soybean curd) followed
      by aging in brine containing salt and alcohol. The present review is based on
      scientific data published in Chinese and international sources. Several types of
      sufu can be distinguished, according to processing method or according to colour
      and flavour. Choice of processing can result in mould fermented sufu, naturally
      fermented sufu, bacterial fermented sufu, or enzymatically ripened sufu.
      Depending on the choice of dressing mixture, red, white or grey sufu may be
      obtained. The stages of the process are discussed and include the preparation of
      tofu, the preparation of pehtze, salting and ripening. Fungal starters include
      Actinomucor spp., Mucor spp. and Rhizopus spp. The chemical composition is
      discussed with particular reference to the proximate composition, the amino acid
      content and profile, as well as the volatile flavour components of various types
      of sufu.

PMID- 11322692
TI  - Surface characteristics of Bacillus cereus and its adhesion to stainless steel.
AB  - The ability of a Bacillus cereus strain, isolated from spoiled milk, to adhere to
      the surface of stainless steel chips was evaluated during its growth in diluted
      tryptic soy broth (DTSB). The number of cells that adhered to the surface
      increased markedly as the culture reached the end of the log phase and entered
      stationary phase, and continued to increase with further incubation. The surface
      properties of cells from the log, stationary, and late stationary phases were
      measured by hydrophobic interaction chromatography (HIC) and electrostatic
      interaction chromatography (ESIC). It was found that surface hydrophobicity of B.
      cereus vegetative cells from the late stationary phase was the highest followed
      by those from the stationary phase and the log phase cultures. While the
      vegetative cells prepared from stationary phase and log phase cultures,
      respectively, had the highest and the lowest surface charges. Adhesion of B.
      cereus vegetative cells to stainless steel was positively correlated with the
      cell surface hydrophobicity (R = 0.979). Surface hydrophobicity and surface
      positive charge noted on the spores harvested from diluted tryptic soy agar
      (DTSA) and Mn2+-tryptone glucose extract agar were higher than those harvested
      from the sucrose or lactose-added DTSA. A wide variation in the surface charge
      values was noted on the surface of various spores prepared from cultures grown on
      the four different media tested, while their ability to adhere to stainless steel
      chips in phosphate buffered saline (PBS) showed no significant difference (p >
      0.05). Similarly, the number of spores or vegetative cells adhering to stainless
      steel suspended in PBS, milk or diluted milk (1000 x) did not differ
      significantly (p > 0.05).

PMID- 11322693
TI  - Membrane inlet mass spectrometric measurement of O2 and CO2 gradients in cultures
      of Lactobacillus paracasei and a developing Cheddar cheese ecosystem.
AB  - Membrane inlet mass spectrometry was used to measure O2 and CO2 as depth profiles
      in stab cultures of 0.1% agar Man Rogosa Sharpe medium inoculated with
      Lactobacillus paracasei CI3. Diffusion of CO2 from the central column of growth
      into the medium was observed to show lower concentrations where bacteria were
      absent. CO2 profiles developed in a manner similar to those in Cheddar cheese and
      O2 was undetectable at similar depths. Gases were analysed in Cheddar cheese over
      a maturation period of 200 d. O2 was detectable to depths of 13, 6 and 2.5 mm on
      days 2, 9 and 15, respectively, but then became undetectable at depths of 2.5-3
      mm. CO2 concentrations measured within the cheese increased 10-fold from day 2 to
      day 200 to reach a value of around 15 mM. The progress of measured CO2
      concentration over time at a given depth in cheese shows a hyperbolic type
      increase. Coefficient of regression values increase with depth to a maximum value
      of R2 = 0.93. In both systems, reductions and increases in CO2 were due to the
      absence or presence of bacterial growth, respectively. Confocal scanning laser
      and scanning electron microscopy was used to show spatial heterogeneity of
      microcolonies within the cheese ecosystem. This information can potentially be
      used as a non-sensory evaluation of cheese maturity status. Measurement of gases
      in a cheese ecosystem provides the first description of mass spectrometry being
      used to monitor the processes of microbial gaseous exchange with respect to O2
      and CO2 in a cheese ecosystem.

PMID- 11322694
TI  - Effect of the interaction between a low tyramine-producing Lactobacillus and
      proteolytic staphylococci on biogenic amine production during ripening and
      storage of dry sausages.
AB  - The interaction between tyrosine-decarboxylase and proteolytic activities of a
      Lactobacillus curvatus and Staphylococcus xylosus, respectively, on biogenic
      amine production during the ripening and the storage of dry fermented sausages
      was investigated. Water content, pH, proteolysis parameters, microbial counts,
      and biogenic amine contents were monitored in spontaneously and starter fermented
      sausages. The use of proteolytic staphylococci as starter resulted in a higher
      content of non-protein nitrogen and total free amino acids. Tyramine was the main
      amine produced in all batches. However, tyrosine-decarboxylase activity of the L.
      curvatus starter strain was weak and yielded lower amounts of tyramine than those
      produced by the wild mioroflora in the control batch. Association between
      tyramine production and proteolysis could only be established in a defectively
      dried batch. Putrescine and cadaverine accumulation was efficiently reduced in
      the starter-mediated fermentation, in agreement with the lower development of
      enterobacteria. Phenylethylamine and tryptamine were only detected in the
      spontaneously fermented sausages, while histamine, spermine and spermidine did
      not vary during the ripening. Biogenic amine levels and related parameters showed
      significant changes during the storage of dry sausages depending on the
      temperature and the batch. As a general rule, changes in the pH, proteolysis,
      microbial counts, and biogenic amine contents were stronger at 19 degrees C than
      at 4 degrees C. The results suggest that refrigeration would be advisable for
      preventing further accumulation of biogenic amines during the storage of dry
      fermented sausages.

PMID- 11322695
TI  - Inhibition of Escherichia coli by dimethyl fumarate.
AB  - The antibacterial activity of dimethyl fumarate (DMF) and six other compounds
      against Escherichia coli (E. coli, K12) was investigated in culture media and
      compared. DMF was found to be more efficient than any other compound at the
      concentration of 200 ppm. The inhibitory activity of DMF against E. coli
      increased with increasing concentration of DMF. DMF also exhibited more obvious
      inhibition against E. coli at the initial growth phase than at other phases. The
      antibacterial ability of DMF showed low stability to heat processing but was less
      sensitive to pH values. Under conditions of restricted availability of oxygen, E.
      coli was more sensitive to DMF. The results indicate that DMF may be a
      potentially effective alternative antimicrobial agent to inhibit E. coli.

PMID- 11322696
TI  - Effects of high-pressure carbon dioxide on Escherichia coli in nutrient broth and
      milk.
AB  - Bactericidal effects of high-pressure carbon dioxide against Escherichia coli
      were studied under 100, 75, 50 and 25 bar at 20 degrees C, 30 degrees C and 40
      degrees C. E. coli suspended in nutrient broth (NB, pH = 6.75) was inactivated
      under 100, 75, 50, and 25 bar CO2 treatments for 50, 65, 100, and 140 min at 30
      degrees C, respectively. Acidification of nutrient broth by dissolved CO2 alone
      might account for the bactericidal effect under pressure. E. coli was inactivated
      in NB with initial pH 5.50 and 4.5 at 100 bar for 80 and 95 min, respectively.
      Treatment at 100 bar CO2 pressure for 6 h caused a decrease of 6.42 and 7.24 log
      cycles in whole and skim milk, respectively.

PMID- 11322697
TI  - Occurrence of fumonisin B1 in maize imported into Taiwan.
AB  - Samples of maize imported into Taiwan during 1997-1998 were collected and
      analyzed for the presence of fumonisin B1 (FB1) using high performance liquid
      chromatography. Eight (6.8%) of 118 samples were found to contain FB1 (334-1614
      microg kg(-1)). The frequency of FB1 found in maize samples imported from
      Australia was 20%, followed by Thailand (10%), and USA (5.1%). In analyzing the
      distribution pattern, it was found that 93.2% of the samples had FB1
      concentrations below 100 microg kg(-1), and only 3.4% (or four samples) were in
      excess of 300 microg kg(-1).

PMID- 11322698
TI  - Detection of moulds producing aflatoxins in maize and peanuts by an immunoassay.
AB  - An enzyme-linked immunosorbent assay (ELISA) was developed to detect moulds
      producing aflatoxins in maize and peanuts by an antibody produced to
      extracellular antigen from Aspergillus parasiticus. This antibody recognized
      species with phenotypic similarities to A. parasiticus, A. flavus and the
      domesticated species A. sojae and A. oryzae. For maize samples that were
      naturally contaminated with aflatoxins, low and high levels of aflatoxin
      corresponded with low and high ELISA readings for mould antigens, respectively.
      Maize and peanuts inoculated with 10(2) spores ml(-1) of A. parasiticus and
      incubated at 15 degrees C for 18 days or 21 degrees C for 7 days were analyzed
      for mould antigens and aflatoxin levels. At 15 degrees C, mould antigens were
      detected by day 4 in maize when 0.16 ng g(-1) of aflatoxin was detected by ELISA
      but not by thin layer chromatography (TLC). Antigens were detected in peanuts by
      day 4 before aflatoxin was found. Likewise, at 21 degrees C, antigens were
      detected by day 4 in maize when less than 1 ng g(-1) of aflatoxin was detected by
      ELISA but not by TLC, but by day 2 in peanuts when no aflatoxin was detected. A.
      parasiticus could be detected before it could produce aflatoxins. Therefore, this
      ELISA shows potential as an early detection method for moulds that produce
      aflatoxins.

PMID- 11322699
TI  - Production of ochratoxin A by Aspergillus carbonarius on coffee cherries.
AB  - Robusta coffee cherries collected before and during sun drying from two coffee
      farms in Thailand were examined for moulds producing ochratoxin A (OA).
      Aspergillus ochraceus was only detected in one sample, whereas Aspergillus
      carbonarius was isolated from 7 out of 14 samples. On gamma-irradiated coffee
      cherries, each of the six tested A. carbonarius strains produced OA. More than
      4800 microg kg(-1) of toxin were detected under optimal conditions (25 degrees C,
      a(w) 0.99). OA production was strongly reduced (230 microg kg(-1)) at an a(w) of
      0.94.

PMID- 11322700
TI  - Dynamics of the microbial community responsible for traditional sour cassava
      starch fermentation studied by denaturing gradient gel electrophoresis and
      quantitative rRNA hybridization.
AB  - The microbial community developing during the spontaneous fermentation of sour
      cassava starch was investigated by cultivation-independent methods. Denaturing
      gradient gel electrophoresis (DGGE) of partially amplified 16S rDNA followed by
      sequencing of the most intense bands showed that the dominant organisms were all
      lactic acid bacteria (LAB), mainly close relatives of Bifidobacterium minimum,
      Lactococcus lactis, Streptococcus sp., Enterococcus saccharolyticus and
      Lactobacillus plantarum., Close relatives of Lb. panis, Leuconostoc mesenteroides
      and Ln. citreum were also found. A complementary analysis using hybridization of
      16S rRNA with phylogenetic probes was necessary to detect the presence of the
      recently discovered species Lb. manihotivorans. Although it represented up to 13%
      of the total lactic acid bacteria of sour cassava starch, this species could not
      be detected by DGGE as the PCR product migrated to the same position as Lc.
      lactis. In addition, it was shown that a strong pH decrease in the time course of
      fermentation was most probably responsible for the competitive selection of acid
      resistant LAB vs. both homo and heterofermentative acid-sensitive LAB.

PMID- 11322701
TI  - PulseNet standardized protocol for subtyping Listeria monocytogenes by
      macrorestriction and pulsed-field gel electrophoresis.
AB  - PulseNet is a national network of pubic health and food regulatory laboratories
      established in the US to detect clusters of foodborne disease and respond quickly
      to foodborne outbreak investigations. PulseNet laboratories currently subtype
      Escherichia coli O157:H7, non-typhoidal Salmonella, and Shigella isolates by a
      highly standardized 1-day pulsed-field gel electrophoresis (PFGE), and exchange
      normalized DNA "fingerprint" patterns via the Internet. We describe a
      standardized molecular subtyping protocol for subtyping Listeria monocytogenes
      that was recently added to PulseNet. The subtyping can be completed within 30 h
      from the time a pure culture of the bacteria is obtained.

PMID- 11322702
TI  - Characterization of a lytic Lactobacillus plantarum bacteriophage and molecular
      cloning of a lysin gene in Escherichia coli.
AB  - Bacteriophage SC921, which can infect Lactobacillus plantarum specifically, was
      isolated from a fermented vegetable source, Kimchi. This phage is active against
      six of 11 strains of L. plantarum tested as hosts. Morphologically, it has an
      isometric head (60 nm in diameter) and a non-contractile tail (260 nm long and 9
      11 nm wide), indicating that it belongs to Bradley's group B or the Siphoviridae
      family according to the International Committee on Taxonomy of Viruses (ICTV).
      The bouyant density was 1.58 g/cm3. SDS-PAGE experimentation indicated that the
      phage particle contains two major structural proteins and several minor proteins.
      The genome was a double stranded linear DNA molecule with cohesive ends and 66.5
      kb long by mapping genomic DNA digested with the restriction endonucleases: KpnI,
      SmaI, and XbaI. The [G + C] content of the phage DNA is 39.4%. For this lysin
      gene study, 9.4 kb of KpnI-digested DNA fragment was cloned into pUC19 and
      expressed in Escherichia coli. The KpnI fragment was considered as the genetic
      element responsible for the lysis gene of L. plantarum bacteriophage. The cloned
      fragment in pUC19 was hybridized to a 9.4-kb fragment generated by KpnI digestion
      of SC 921 as a probe. This confirmed that the fragment in pUC19 originated from
      phage DNA. The lysin gene was near the middle of the phage genome.

PMID- 11322703
TI  - Occurrence of Listeria species in retail poultry meat and comparison of a
      cultural/immunoassay for their detection.
AB  - The prevalence of Listeria spp. on the skin of a hundred fresh chicken carcasses
      purchased from 20 retail stores in Leon was investigated using the routine test
      procedure recommended by the United States Department of Agriculture (USDA).
      PALCAM and Modified Oxford agar (MOX) were used for isolation. Listeria spp.,
      Listeria monocytogenes, L. innocua, L. welshimeri, L. grayi and L. ivanovii were
      present in 95%, 32%, 66%, 7%, 4% and 2% of the samples, respectively. Next, an
      immunoassay test (Listeria Rapid Test; Oxoid, Unipath) and the routine test
      procedure (USDA) were compared for their ability to detect Listeria spp. on 40
      chicken carcasses. When we used MOX for the isolations, the sensitivity of the
      immunoassay test was 100% and the specificity 85.7%. When we used PALCAM medium
      the sensitivity and specificity of the test was 94.29% and 80%, respectively.

PMID- 11322704
TI  - Diversity of Listeria monocytogenes isolates from cold-smoked salmon produced in
      different smokehouses as assessed by Random Amplified Polymorphic DNA analyses.
AB  - One hundred and forty-eight Listeria monocytogenes isolates originating from
      vacuum packed cold-smoked salmon produced in 10 different Danish smokehouses were
      compared by Random Amplified Polymorphic DNA (RAPD) profiling. A total of 16
      different reproducible RAPD profiles were obtained using a standardised RAPD
      analysis by four primers separately. The grouping of the 148 strains was exactly
      the same for the four primers used. For a sub-set of 20 strains typed by Pulsed
      Field Gel Electrophoresis (PFGE), only one strain was allocated into a different
      group as compared to the grouping by RAPD typing. Different RAPD types dominated
      in products from different smokehouses. Some identical RAPD types were isolated
      in several smokehouses. In each of four smokehouses, one particular RAPD type
      could be repeatedly isolated from products. Each smokehouse/product carried its
      own specific RAPD type and this may indicate a possible persistence of closely
      related strains of L. monocytogenes in smokehouses.

PMID- 11322705
TI  - Uptake of choline from salmon flesh and its conversion to glycine betaine in
      response to salt stress in Shewanella putrefaciens.
AB  - When cultured in M63 minimal medium plus 0.6 M NaCl, the growth of Shewanella
      putrefaciens was strongly inhibited. The addition of an extract from smoked
      salmon to this medium restored the growth almost to the unstressed level. A
      comparison of the 13C NMR spectra of intracellular solutes extracted from S.
      putrefaciens cells cultured in both conditions revealed the accumulation of
      glycine betaine (GB) from the smoked salmon extract (SSE). Analysis of the
      osmoprotective properties of this extract for several strains of Escherichia coli
      (which differ from each other in their ability to accumulate GB (i) from the
      surrounding environment, and (ii) from its hydroxylated precursor choline),
      demonstrated the absence of GB in the SSE. From the overall results, we inferred
      that salt-stressed S. putrefaciens cells accumulated GB from choline present in
      the SSE. Furthermore, the use of [14C]-labeled betaines gave evidence that S.
      putrefaciens (i) oxidised choline to GB, (ii) accumulated GB as a non
      metabolisable osmolyte (up to 1300 nmol (mg dw)(-1) when cultured in a medium
      containing 0.5 M NaCl and either 1 mM choline or 1 mM GB), and (iii) both choline
      and GB uptake activities were osmotically upregulated (both activities were
      increased more than 50-fold in media containing 0.4 to 0.6 M NaCl). In all, our
      results suggest that in salted smoked salmon, S. putrefaciens imports and
      oxidises choline, leading to the intracellular accumulation of GB.

PMID- 11322706
TI  - Uridine receptor: discovery and its involvement in sleep mechanism.
AB  - This review deals with the concept of sleep mechanism based on our uridine
      receptor theory. It is well established that uridine is one of the sleep
      promoting substances, we have, therefore, synthesized new types of hypnotic
      compounds from oxopyrimidine nucleosides. Their mechanism of action in CNS
      depressant effects is elucidated based on the receptor theory. In this study,
      structure-activity relationship for CNS depressant properties, sleep-promoting
      effects, interaction with certain CNS receptors, and receptor binding assay of
      uridine derivatives as oxopyrimidine nucleoside were investigated. In the studies
      of structure-activity relationship of N3-substituted uridine, we found for the
      first time that both N3-benzyluridine and N3-phenacyluridine synthesized
      exhibited potent hypnotic activity (loss of righting reflex) by
      intracerebroventicular injection in mice. Moreover, certain derivatives of these
      compounds possessed synergistic effects with barbiturate and benzodiazepine, and
      decreased in spontaneous activity, motor incoordination, and antianxiety effects
      in mice. Especially, N3-phenacyluridine markedly enhanced pentobarbital- and
      diazepam-induced sleep by 6- and 70-fold, respectively. However, N3-benzyluracil
      and N3-phenacyluracil that have no ribose moiety did not possess any hypnotic
      activity, indicating specific effects of nucleoside derivatives. Effects of N3
      benzyluridine on natural sleep in rats were thus examined. N3-Benzyluridine also
      possessed the sleep promoting effect assessed by electrocorticogram at the dose
      of 10 pmol. For elucidating the mechanism of action of N3-phenacyluridine, the
      interactions of this compound with benzodiazepine, GABA, 5-HT, or adenosine
      receptors were also investigated. Although the pharmacological activity of N3
      phenacyluridine was high, the affinities to benzodiazepine, GABA, 5-HT, and
      adenosine receptors were quite low. [3H]N3-Phenacyluridine concentration
      dependently bound to synaptic membrane prepared from the bovine brain. The
      Scatchard analysis revealed a single component of the binding site. This binding
      site is proposed here as a novel receptor called "uridine receptor" for hypnotic
      activity of the uridine derivatives. The rank order of the distribution of these
      specific binding sites was found to be striatum > thalamus > cerebral cortex >
      cerebellum > mid brain > medulla oblongata in the rat brain. In the metabolic
      study of N3-phenacyluridine, we found that this compound was exclusively
      metabolized to N3-(S)-(+)-alpha-hydroxy-beta-phenethyluridine, but not the (R)-
      form, in mice. N3-(S)-(+)-alpha-Hydroxy-beta-phenylethyluridine possessed not
      only strong hypnotic activity but also a high affinity to the uridine receptor of
      synaptic membranes, while the (R)-isomer was low in both activities. Racemic
      mixture was shown to be intermediate for pharmacological effects of the
      compounds. These studies which used (R)- or (S)-isomer indicate that uridine
      binding site or uridine receptor, exists in the CNS and plays some role in sleep
      regulation in mammals as one of the triggering steps in inducing hypnotic
      activity. It is suggested that uridine is released from steps of nucleic acid
      nucleic protein biosynthesis (catabolism), and reaches the binding sites in the
      areas of the brain which regulate natural sleep. The uridine dissociated from the
      receptor is then utilized for the synthesis of nucleic acid (anabolism). We
      propose here that the induction of sleep may be mediated by uridine through
      uridine receptor in the CNS, although the structure of uridine receptor is not
      yet elucidated.

PMID- 11322707
TI  - Sleep modifies glutamate decarboxylase mRNA within the barrel cortex of rats
      after a mystacial whisker trim.
AB  - STUDY OBJECTIVES: Determine the effects of time of day and sleep deprivation on
      glutamate decarboxylase 67,000 MW (GAD67) mRNA during cortical synaptic
      reorganization induced by a unilateral trimming of the mystacial vibrissae in
      rats. DESIGN: Two experiments were conducted--One measured GAD67 mRNA in the
      barrel cortex at 3 or 6 h after a unilateral whisker cut at either light or dark
      onset; the other measured GAD67 mRNA after a unilateral whisker cut at light
      onset with or without sleep deprivation. SETTING: University-based Research
      Laboratory. PARTICIPANTS: Sprague-Dawley rats (250-350 g). INTERVENTIONS: N/A.
      MEASUREMENTS AND RESULTS: The reverse transcriptase polymerase chain reaction was
      used to measure the time of day changes in GAD67 mRNA after a unilateral whisker
      cut. GAD67 mRNA decreased in the barrel cortex at 3 and 6 h after a whisker trim
      at dark onset when the rats were mainly awake. No changes were observed in GAD67
      mRNA levels after a whisker cut at light onset, a time when the rats mainly
      sleep. In situ hybridization for GAD67 mRNA supported these findings; no changes
      in GAD mRNA occurred in layer 4 of the barrel cortex that received input from the
      mystacial whiskers that were trimmed at light onset. However, when the rats were
      sleep-deprived, GAD67 mRNA increased in the barrel cortex receiving input from
      the lip hairs surrounding the trimmed mystacial whiskers. CONCLUSIONS: These data
      imply that sleep modifies GAD67 mRNA expression and that this effect is dependent
      upon the nature of the ongoing synaptic reorganization. They support the notion
      that sleep serves a synaptic function.

PMID- 11322708
TI  - Using melatonin to chase away the monday morning blues.

PMID- 11322709
TI  - A single dose of melatonin prevents the phase delay associated with a delayed
      weekend sleep pattern.
AB  - STUDY OBJECTIVES: This study was designed to test the hypotheses that a delayed
      weekend sleep pattern may lead to a phase delay of the endogenous circadian
      rhythm, and that melatonin administration can counteract the phase delay and
      prevent the sleep and functional impairments associated with this sleep pattern.
      DESIGN: A within-subject, counterbalanced design was used in which each subject
      participated in both placebo and melatonin conditions. Subjects' sleep-wake
      schedules were delayed by two hours on Friday and Saturday to simulate the
      delayed weekend sleep pattern. Six mg of melatonin or a placebo pill was
      administered double blind on Sunday late afternoon. SETTING: N/A. PARTICIPANTS:
      Ten healthy volunteers (mean age = 22.1 years old). MEASUREMENTS AND RESULTS:
      Salivary dim-light melatonin onset (DLMO) was measured on Friday and Monday
      nights. Subject's sleep was recorded with polysomnography on Sunday night and
      their levels of sleepiness, cognitive functioning and mood were assessed on
      Sunday night and Monday morning. Results show that the delayed weekend sleep
      pattern caused a 31.6 min delay of the endogenous melatonin rhythm. Melatonin
      administration counteracted the phase delay of endogenous melatonin onset. On
      Sunday, melatonin administration increased the sleepiness throughout the evening
      and reduced sleep onset latency at bedtime. On Monday morning, subjective
      sleepiness was decreased in the melatonin condition. CONCLUSION: A delayed
      weekend sleep pattern did show a mild phase-delay effect on the endogenous
      circadian rhythm. A single dose of melatonin can acutely reverse the weekend
      drift.

PMID- 11322710
TI  - Stimulant and anticataplectic effects of reboxetine in patients with narcolepsy:
      a pilot study.
AB  - STUDY OBJECTIVES: To investigate potential stimulant and anticataplectic effects
      of 10 mg reboxetine in patients diagnosed with narcolepsy. DESIGN: 12 patients
      were treated for a 2-week period with 10 mg reboxetine under open conditions. The
      dosage of reboxetine was gradually increased between Day 1 and Day 9. Outcome
      parameters consisted of nightime polysomnography (PSG), Multiple Sleep Latency
      Test (MSLT), Epworth Sleepiness Scale (ESS), Visual Analog Scale for Sleepiness
      (VAS), Ullanlinna Narcolepsy Scale (UNS), and the Beck Depression Inventory
      (BDI). SETTING: Sleep Disorders Clinic at a University Hospital. PATIENTS: 12
      patients meeting ICSD-criteria for narcolepsy. INTERVENTIONS: Pharmacological
      treatment with reboxetine. RESULTS: Following treatment for two-weeks, a
      significant improvement in daytime sleepiness could be observed, as reflected by
      a mean decrease of 48.6% on the Epworth Sleepiness Scale and a mean increase of
      54.7% in sleep latency on the MSLT. Furthermore, a significant reduction in the
      cataplexy subscore of the Ullanlinna Narcolepsy Scale and in REM-sleep was found.
      CONCLUSIONS: Our results suggest that reboxetine exerts stimulant and
      anticataplectic effects in narcolepsy. Contrary to previous thinking, by which
      stimulant action would require dopaminergic facilitation, noradrenergic
      mechanisms might be relevant to the control of wakefulness.

PMID- 11322711
TI  - Impact of reduced reverberation time on sound-induced arousals during sleep.
AB  - The effect of reducing reverberation time was studied in 12 subjects during
      sleep. EEG-arousals following specific sound stimuli were significantly reduced
      (p<0.007) when reverberation time was reduced with sound-absorbing ceiling-tiles.
      On average reverberation was reduced 0.124 seconds at similar sound levels. It is
      proposed that increased sound absorption, i.e. reduced reverberation time, by
      contributing to a better acoustic environment may reduce sound-induced sleep
      fragmentation.

PMID- 11322712
TI  - The short-term benefits of brief and long naps following nocturnal sleep
      restriction.
AB  - STUDY OBJECTIVES: The purpose was to remedy the lack of experimental studies
      directly comparing the effects of brief and long daytime naps following nocturnal
      sleep restriction. DESIGN: Twelve young adult healthy sleepers participated in a
      repeated measures design comparing the effects of no nap, a 10-minute nap, and a
      30-minute afternoon nap in each case following a night of 4.7 hours of total
      sleep time. Objective and subjective alertness measures and cognitive performance
      measures were taken before, then 5, 35, and 60 minutes after the termination of
      the nap. SETTING: N/A. PARTICIPANTS: N/A. INTERVENTIONS: N/A. MEASUREMENTS AND
      RESULTS: In the no nap condition measures showed either no change or a decreases
      of alertness and performance across the testing period. Following the 10-minute
      nap there was an immediate improvement in subjective alertness and cognitive
      performance which was sustained for the hour of post nap testing. Immediately
      following the 30 minute nap most measures of alertness and performance declined
      but showed some recovery by the end of testing. CONCLUSIONS: Because the delayed
      benefits following the 30-minute nap may be due to sleep inertia, longer post-nap
      testing periods should be investigated. However, we conclude that the detrimental
      effects of sleep restriction were more rapidly and significantly ameliorated, at
      least within the hour following the nap, by a 10-minute afternoon nap.

PMID- 11322713
TI  - Actigraphy and parental ratings of sleep in children with attention
      deficit/hyperactivity disorder (ADHD).
AB  - STUDY OBJECTIVES: To assess various sleep parameters in latency-aged children
      with ADHD and their normally developing peers through the use of multiple sleep
      measures. DESIGN: Six sleep parameters were evaluated for two groups of children,
      ADHD and normal comparison. Each group consisted of 25 children (20 males, 5
      females) who ranged in age from 7 to 11 years. All children underwent rigorous
      diagnostic procedures and the ADHD subjects were selected only if they displayed
      pervasiveness in their symptomatology and were medication naive. Parents
      completed a retrospective questionnaire which evaluated sleep problems over the
      past six months. Additionally, each child wore an actigraph for seven consecutive
      nights, and the child's parents completed a sleep diary during this time period.
      SETTING: N/A. PATIENTS OR PARTICIPANTS: N/A. INTERVENTIONS: N/A. RESULTS: Based
      on the findings from the questionnaire, parents of children with ADHD reported
      significantly more sleep problems than parents of normally developing children.
      However, the majority of these sleep differences were not verified through
      actigraphy or sleep diary data, with the exception of longer sleep duration for
      children with ADHD and parent reports that describe increased bedtime resistence.
      It was also found that child-parent interactions during bedtime routines were
      more challenging in the ADHD group. CONCLUSIONS: Despite the possibility of
      intrinsic sleep problems such as longer sleep duration, results indicate that
      many of the sleep problems of children with ADHD may be due to challenging
      behaviours during bedtime routines. The reason for discrepancies among sleep
      studies employing objective measures as well as between retrospective and
      prospective measures are discussed.

PMID- 11322714
TI  - Hyperactivity and polysomnographic findings in children evaluated for sleep
      disordered breathing.
AB  - STUDY OBJECTIVES: Children with sleep-disordered breathing (SDB) or periodic leg
      movements during sleep (PLMS) often have hyperactive behavior that improves when
      the sleep disorder is treated. Some children with SDB also have PLMS. To
      determine what polysomnographic features of SDB might be associated with
      hyperactive behavior, we studied behavior, SDB, and PLMS in a series of patients.
      DESIGN: Prospective and observational. SETTING: University-based sleep disorders
      laboratory. SUBJECTS: Children (n=113) aged 2 to 18 years, referred for suspected
      SDB. INTERVENTIONS: Parents completed the hyperactivity index of the Connors'
      Parental Rating Scale, and results were converted to age-adjusted t-scores.
      Children underwent laboratory-based polysomnography, with esophageal pressure
      monitoring when requested (n=19) by referring physicians. RESULTS: Children with
      SDB (n=59) showed high hyperactivity scores (mean 59.5+/-18.3 SD, 95% C.I. [54.7,
      64.2]) but these scores were no higher than those of children without SDB (59.0+/
      15.1, [54.8, 63.1]). Hyperactivity showed no significant associations with the
      rate of apneas and hypopneas, minimum oxygen saturation, or most negative
      esophageal pressure (p>0.10), but was associated with the presence of 5 or more
      PLMS per hour (p=0.02). The rate of PLMS showed a linear association with
      hyperactivity among those subjects with SDB (p = 0.002), but no association among
      those subjects without SDB (p = 0.64). CONCLUSIONS: These findings suggest that
      hyperactive behavior is common among children referred for suspected SDB,
      regardless of the presence or severity of SDB. Current observations cannot prove
      causality, but they are consistent with the hypothesis that PLMS may contribute
      to hyperactivity and SDB may act as an effect modifier.

PMID- 11322715
TI  - Childhood narcolepsy in North China.
AB  - STUDY OBJECTIVES: The purpose is to report the results of an effort to diagnose
      children with narcolepsy in a pediatric referral clinic. DESIGN: Between
      September 1998 and December 1999, a program was implemented to emphasize
      recognition of childhood narcolepsy. Patients underwent brain computed tomography
      (CT) scan and magnetic resonance imaging (MRI) testing. All children received a
      MSLT test following a routine night's sleep, and serological HLA typing for HLA
      DR2. Three who reported occasional snoring also underwent nocturnal PSG prior to
      the MSLT. SETTING: N/A. PATIENTS OR PARTICIPANTS: N/A. INTERVENTIONS: N/A.
      MEASUREMENTS AND RESULTS: 29 (21 male, 8 female) children were identified with
      sleepiness and cataplexy. There was no evidence for brain functional or
      structural disease or for drug use. Sleep paralysis was elicited in 41%;
      hypnagogic hallucinations, in 59%. Psychosocial problems including emotional
      irritability and social isolation were present in 93% of the patients. Mean sleep
      latency on MSLT was 2.0+/-1.3 minutes; sleep-onset rapid eye movement (SOREM)
      occurred during 2/5 naps in 28 of 29 patients and 3/5 in 26/29 patients. The
      average number and latency of SOREM episodes were 4.2+/-0.9 episodes and 4.0+/
      1.7 minutes, respectively. In those with snoring, a nocturnal PSG did not
      disclose sleep apneas/hypopneas. All patients but one were HLA DR2 positive. The
      estimated clinic incidence was 0.04%. CONCLUSIONS: A program for recognition in a
      referral neurology clinic combined with an availability of the MSLT and HLA
      testing resulted in the new identification in North China of a number of children
      with narcolepsy syndromes.

PMID- 11322716
TI  - Ambient temperature is associated with changes in infants' arousability from
      sleep.
AB  - STUDY OBJECTIVE: To evaluate the influence of ambient temperature on infants'
      arousability from sleep. DESIGN: Two groups of healthy infants with a median age
      of 11 weeks were recorded polygraphically during one night: 31 infants were
      studied at 24 degreesC and 31 infants at 28 degreesC. To determine their arousal
      thresholds, the infants were exposed to white noises of increasing intensities
      during REM and NREM sleep. Arousal thresholds were defined by the auditory
      stimuli needed to induce arousals. SETTING: N/A. PATIENTS OR PARTICIPANTS: N/A.
      INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: The arousal thresholds decreased
      across the night in the infants sleeping at 24 degreesC (p=.017). The finding was
      not found for the infants sleeping at 28 degreesC. When analyzing the arousal
      responses according to time of the night, it was found that the auditory
      thresholds were significantly higher at 28 degreesC than at 24 degreesC between
      03:00 hr and 06:00 hr (p=.003). These findings were only seen in REM sleep.
      CONCLUSION: High ambient temperature could add to the difficulty to arouse from
      REM sleep in the late hours of the night.

PMID- 11322717
TI  - The influence of lifestyle and health status factors on sleep loss among the
      Japanese general population.
AB  - STUDY OBJECTIVE: To examine the relationship between lifestyle, health status
      factors and sleep loss. DESIGN: A cross-sectional questionnaire survey conducted
      by the Ministry of Health and Welfare, Japan. SETTING: N/A. PATIENTS OR
      PARTICIPANTS: Approximately 30,000 subjects selected from the general population
      in Japan. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: This study indicated that
      approximately 28% of the general population sleep less than 6 hours nightly and
      approximately 65% sleep less than 7 hours. However, approximately 80% of the
      population reported getting sufficient sleep. Multiple logistic regression
      analysis showed that being females, being of younger age, living in an urban
      environment, being unemployed, and having an unhealthy lifestyle (i.e., lack of
      exercise, poor health status, and irregular eating habits) were associated with
      sleep loss. CONCLUSION: In this study, sleep loss was found to be associated with
      having an unhealthy lifestyle and being in poor general health. These findings
      suggest that health education and promotion of a healthy lifestyle should be
      advocated.

PMID- 11322718
TI  - The relationship between slow-wave activity, body temperature, and cardiac
      activity during nighttime sleep.
AB  - STUDY OBJECTIVES: Recent work indicates that cardiac sympathetic activity is not
      influenced by the circadian system and instead decreases after sleep onset.
      However, little is known about the pattern of change in cardiac sympathetic
      activity during NREM/REM sleep cycles and whether this is associated with
      alterations in slow-wave activity (SWA). To address these questions, we examined
      SWA, cardiac sympathetic activity, heart rate and rectal and foot temperatures
      during the first three NREM/REM sleep cycles and during transitions between NREM
      and REM sleep. DESIGN: Subjects were required to maintain a constant sleep-wake
      cycle for at least a week and have at least one adaptation night, before their
      night of recording. SETTING: Individual temperature controlled bedrooms.
      PARTICIPANTS: 10 young healthy males and females. INTERVENTIONS: NA. MEASUREMENTS
      AND RESULTS: All variables showed the greatest change in the first NREM cycle.
      Specifically, SWA, sympathetic activity, heart rate and foot temperature
      increased while rectal temperature decreased. After the initial increase, cardiac
      sympathetic activity decreased across the sleep phase, in association with a
      decrease in heart rate. Cardiac sympathetic activity did not significantly alter
      across NREM-REM cycles. CONCLUSIONS: The results suggest that increases in heart
      rate and cardiac sympathetic activity early in the sleep period are, in part, a
      compensatory reaction to the concomitant thermoregulatory changes observed. These
      results also indicate that the effect of time asleep on cardiac sympathetic
      activity may be greater than the influence of sleep cycles. These results are
      discussed with reference to the recuperative value of naps.

PMID- 11322719
TI  - Intracellular and extracellular regulation of ureteric bud morphogenesis.
AB  - The urinary collecting duct system of the permanent kidney develops by growth and
      branching of an initially unbranched epithelial tubule, the ureteric bud.
      Formation of the ureteric bud as an outgrowth of the wolffian duct is induced by
      signalling molecules (such as GDNF) that emanate from the adjacent
      metanephrogenic mesenchyme. Once it has invaded the mesenchyme, growth and
      branching of the bud is controlled by a variety of molecules, such as the growth
      factors GDNF, HGF, TGFbeta, activin, BMP-2, BMP-7, and matrix molecules such as
      heparan sulphate proteoglycans and laminins. These various influences are
      integrated by signal transduction systems inside ureteric bud cells, with the MAP
      kinase, protein kinase A and protein kinase C pathways appearing to play major
      roles. The mechanisms of morphogenetic change that produce branching remain
      largely obscure, but matrix metalloproteinases are known to be necessary for the
      process, and there is preliminary evidence for the involvement of the
      actin/myosin contractile cytoskeleton in creating branch points.

PMID- 11322720
TI  - Fine structure of the developing epidermis in the embryo of the American
      alligator (Alligator mississippiensis, Crocodilia, Reptilia).
AB  - The morphological transition from the simple epidermis that contacts the amniotic
      fluid of embryonic crocodilians to the adult epidermis required in a terrestrial
      environment has never been described. We used light and electron microscopy to
      study the development, differentiation and keratinisation of the epidermis of the
      American alligator, Alligator mississippiensis, between early and late stages of
      embryonic skin formation. In early embryonic development, the epidermis consists
      of a flat bilayer. As it develops, the bilayered epidermis comes to lie beneath
      the peridermis. Glycogen is almost absent from the bilayered epidermis but
      increases in basal and suprabasal cells when scales form. Glycogen disappears
      from suprabasal cells that accumulate keratin. The peridermis and 1 or 2
      subperidermal layers form an embryonic epidermis that is partially or totally
      lost before hatching. These cells accumulate coarse filaments and form reticulate
      bodies. Mucous and lamellate granules are produced in the Golgi apparatus and are
      partly secreted extracellularly. The embryonic cells darken with the formation of
      larger reticulate bodies that aggregate with intermediate filaments and other
      cell organelles, as their nuclear chromatin condenses. Thin beta-cells resembling
      those of scutate scales of birds develop beneath the embryonic epidermis and form
      a stratified beta-layer that varies in thickness in different body regions. The
      epidermis differentiates first in the back, tail and belly. At the beginning of
      beta-cell differentiation, the cytoplasm contains sparse bundles of alpha-keratin
      filaments, glycogen and lipid droplets or vacuoles apparently derived from the
      endoplasmic reticulum and Golgi apparatus. These organelles disappear rapidly as
      irregular bundles of electron-dense beta-keratin filaments accumulate and form
      larger bundles. The larger bundles consist of 3 nm thick electron-pale keratin
      microfibrils and are derived from the assemblage of beta-keratin molecules
      produced by ribosomes. While in mammals the epidermal barrier is formed by alpha
      keratinocytes, in the alligator the barrier is formed by beta-keratin cells. The
      beta-layer is reduced or absent from the small hinge region between scales. In
      the latter areas the barrier is made of alpha or a mixture of alpha/beta
      keratinocytes. Thus alligators resemble birds where the beta-keratin molecules
      are deposited directly over an alpha-keratin scaffold, rather than an initial
      production of beta-keratin packets which then merge with alpha-keratin, as occurs
      in the 'Chelonia and Lepidosauria. The pigmentation of the epidermis of embryos
      is mostly derived from epidermal melanocytes.

PMID- 11322721
TI  - Muscle fibre types in the suprahyoid muscles of the rat.
AB  - Five muscle fibre types (I, IIc, IIa, IIx and IIb) were found in the suprahyoid
      muscles (mylohyoid, geniohyoid, and the anterior and posterior bellies of the
      digastric) of the rat using immuno and enzyme histochemical techniques. More than
      90% of fibres in the muscles examined were fast contracting fibres (types IIa,
      IIx and IIb). The geniohyoid and the anterior belly of the digastric had the
      greatest number of IIb fibres, whilst the mylohyoid was almost exclusively formed
      by aerobic fibres. The posterior belly of the digastric contained a greater
      percentage of aerobic fibres (83.4%) than the anterior belly (67.8%). With the
      exception of the geniohyoid, the percentage of type I and IIc fibres, which have
      slow myosin heavy chain (MHCbeta), was relatively high and greater than has been
      previously reported in the jaw-closing muscles of the rat, such as the
      superficial masseter. The geniohyoid and mylohyoid exhibited a mosaic fibre type
      distribution, without any apparent regionalisation, although in the later MHCbeta
      containing fibres (types I and IIc) were primarily located in the rostral 2/3
      region. In contrast, the anterior and posterior bellies of the digastric revealed
      a clear regionalisation. In the anterior belly of the digastric 2 regions were
      observed: both a central region, which was almost exclusively formed by aerobic
      fibres and where all of the type I and IIc fibres were located, and a peripheral
      region, where type IIb fibres predominated. The posterior belly of the digastric
      showed a deep aerobic region which was greater in size and where type I and IIc
      fibres were confined, and a superficial region, where primarily type IIx and IIb
      fibres were observed.

PMID- 11322722
TI  - Quantification of fibre type regionalisation: an analysis of lower hindlimb
      muscles in the rat.
AB  - Newly developed concepts and methods for the quantification of fibre type
      regionalisation were used for comparison between all muscles traversing the ankle
      of the rat lower hindlimb (n = 12). For each muscle, cross-sections from the
      proximodistal midlevel were stained for myofibrillar ATPase and classified as
      type I ('slow') or II ('fast'). For the 11 'fast' muscles (i.e. all except
      soleus), the muscle outline and the position of each type I fibre were digitised
      for further computer processing. Two potentially independent aspects of type I
      fibre regionalisation were evaluated quantitatively: (1) the degree to which type
      I fibres were restricted to a limited portion of the total cross-sectional area
      ('area-regionalisation'): (2) the extent and direction of the difference (if any)
      between the centre of the muscle cross-section and the calculated centre for the
      type I fibre cluster ('vector regionalisation'). Statistical analysis showed that
      type I fibres were vector regionalised in practically all investigated muscles
      and area regionalised within most of them, the only consistent exceptions being
      peroneus brevis and peroneus digitorum 4, 5. In muscles with a high degree of
      area regionalisation the population of type I fibres also had a markedly
      eccentric intramuscular position (i.e. high vector regionalisation). A
      significant relationship was observed between the relative position of a muscle
      within the hindlimb (transverse plane) and the direction and degree of its type I
      fibre eccentricity. On average, the degree of type I fibre eccentricity was
      greater for muscles remote from the limb centre than for those situated more
      centrally. In addition, the intramuscular concentration of type I fibres was
      typically greatest towards the centre of the limb, the most striking exception
      being tibialis posterior. For the slow soleus muscle, which is centrally placed
      within the limb, our analysis concerned the type II fibres, which were found to
      be weakly vector regionalised but not significantly area regionalised. It is
      concluded that, within muscles of the rat's lower hindlimb, fibre type
      regionalisation is a general and graded phenomenon which may reflect
      differentiating (embryological?) mechanisms of a transmuscular significance.
      Furthermore, the analysis demonstrated the usefulness of our new methods and
      concepts for the quantification of fibre type regionalisation.

PMID- 11322723
TI  - Occurrence and structure of epipharyngeal pouches in bears (Ursidae).
AB  - The infrequent mention of epipharyngeal pouches occurring in some species of
      bears indicates the scarcity of morphological and functional knowledge about
      these structures. In order to provide precise morphological data on the structure
      of these remarkable formations and to verify their taxonomic utility, the
      pharyngeal regions of 1 spectacled bear and 3 brown bears were examined. All
      these individuals possessed epipharyngeal pouches, which are tubular, blind
      ending outpouchings of the caudodorsal pharyngeal wall equipped with respiratory
      epithelium and a thick layer of elastic fibres. While the spectacled bear and
      Ursus arctos syriacus possessed a single pouch on the caudodorsal wall of the
      nasopharynx, in Ursus arctos and Ursus arctos beringianus 2 unequally sized
      pouches were present. Two additional sacs of smaller size, representing
      outpouchings of the lateral pharyngeal wall, occurred in the spectacled bear.
      These findings prove epipharyngeal pouches to be constant and unique
      morphological features of the family Ursidae, the anatomical features suggesting
      involvement in the respiratory system most probably in important aspects of ursid
      phonation. This is the first description of epipharyngeal pouches in the
      spectacled bear.

PMID- 11322724
TI  - Persistent hypoglossal artery.

PMID- 11322725
TI  - Syntheses of neoglycolipids with hexitol spacers between the saccharidic and the
      lipidic parts.
AB  - Four neoglycolipids having 2-amino-2-deoxy-D-glucose or D-galactose moieties
      linked to the lipidic part by a glucitol or a mannitol spacer-arm have been
      synthesized. The key step of the synthetic strategy was the regiospecific or
      regioselective beta-glycosylation of partially protected glucitol or mannitol
      acceptors by either 3,4,6-tri-O-acetyl-2-deoxy-2-iodo-alpha-D-mannopyranosyl
      azide or 2,3,4,6-tetra-O-benzoyl-alpha-D-galactopyranosyl trichloroacetimidate
      donors.

PMID- 11322726
TI  - Synthesis of biotinylated bis(D-glucose) derivatives for glucose transporter
      photoaffinity labelling.
AB  - New diazirine based bis-glucose derivatives for tagging glucose transporters have
      been synthesised. These included two biotinylated compounds linked either by an
      aminocaproate or by a cleavable dithiol link. These compounds have been
      derivatised via a key skeleton compound that can be easily used for introduction
      of additional tags. Studies on the erythrocyte glucose transporter (GLUT1) and
      the insulin-stimulated adipose cell transporter (GLUT4) have revealed the
      biotinylated photoreactive bis-glucose compounds are effective labelling
      reagents.

PMID- 11322727
TI  - Synthesis of chitotetraose and chitohexaose based on dimethylmaleoyl protection.
AB  - tert-Butyldimethylsilyl 3,6-di-O-benzyl-2-deoxy-2-dimethylmaleimido-beta-D
      glucopyranoside was readily transformed into the disaccharide glycosyl donor,
      3,4,6-tri-O-acetyl-2-deoxy-2-dimethylmaleimido-beta-D-glucopyranosyl-(1 --> 4)
      3,6-di-O-benzyl-2-deoxy-2-dimethylmaleimido-alpha/beta-D-glucopyranosyl
      trichloroacetimidate, and the disaccharide glycosyl acceptor, tert
      butyldimethylsilyl 3,6-di-O-benzyl-2-deoxy-2-dimethylmaleimido-beta-D
      glucopyranosyl-(1 --> 4)-3,6-di-O-benzyl-2-deoxy-2-dimethylmaleimido-beta-D
      glucopyranoside. A TMSOTf-catalysed coupling of the acceptor with the donor
      afforded the respective tetrasaccharide derivative, which can be transformed to
      chitotetraose. tert-Butyldimethylsilyl 3,6-di-O-benzyl-2-deoxy-2
      dimethylmaleimido-4-O-phenoxyacetyl-beta-D-glucopyranosyl-(1 --> 4)-3,6-di-O
      benzyl-2-deoxy-2-dimethylmaleimido-beta-D-glucopyranoside was converted into
      donor 3,6-di-O-benzyl-2-deoxy-2-dimethylmaleimido-4-O-phenoxyacetyl-beta-D
      glucopyranosyl-(1 --> 4)-3,6-di-O-benzyl-2-deoxy-2-dimethylmaleimido-beta-D
      glucopyranosyl trichloroacetimidate. Its coupling with benzyl 3,6-di-O-benzyl-2
      deoxy-2-dimethylmaleimido-beta-D-glucopyranosyl-(1 --> 4)-3,6-di-O-benzyl-2-deoxy
      2-dimethylmaleimido-beta-D-glucopyranoside, followed by dephenoxyacetylation,
      gave benzyl 3,6-di-O-benzyl-2-deoxy-2-dimethylmaleimido-beta-D-glucopyranosyl-(1 
      -> 4)-3,6-di-O-benzyl-2-deoxy-2-dimethylmaleimido-beta-D-glucopyranosyl-(1 --> 4)
      3,6-di-O-benzyl-2-deoxy-2-dimethylmaleimido-beta-D-glucopyranosyl-(1 --> 4)-3,6
      di-O-benzyl-2-deoxy-2-dimethylmaleimido-beta-D-glucopyranoside, whose
      glycosylation furnished, after replacement of the DMM-group by the acetyl moiety
      and subsequent deprotection, chitohexaose.

PMID- 11322728
TI  - Enzymatic glycosylation using 6-O-acylated sugar donors and acceptors: beta-N
      acetylhexosaminidase-catalysed synthesis of 6-O,N,N'-triacetylchitobiose and 6'
      O,N,N'-triacetylchitobiose.
AB  - p-Nitrophenyl 6-O-acetyl-2-acetamido-2-deoxy-beta-D-glucopyranoside (5a) was used
      as the glycosyl donor in a beta-N-acetylhexosaminidase-catalysed (from
      Penicillium brasilianum) glycosylation of GlcNAc yielding 6'-O,N,N'
      triacetylchitobiose (6), while 6-O-acetyl-2-acetamido-2-deoxy-beta-D
      glucopyranose (3a) served as a selectively protected acceptor in a
      transglycosylation reaction catalysed by the same enzyme to yield 6-O,N,N'
      triacetylchitobiose (4).

PMID- 11322729
TI  - Phosphorylation and metabolism of sucrose and its five linkage-isomeric alpha-D
      glucosyl-D-fructoses by Klebsiella pneumoniae.
AB  - Not only sucrose but the five isomeric alpha-D-glucosyl-D-fructoses trehalulose,
      turanose, maltulose, leucrose, and palatinose are utilized by Klebsiella
      pneumoniae as energy sources for growth, thereby undergoing phosphorylation by a
      phosphoenolpyruvate-dependent phosphotransferase system uniformly at 0-6 of the
      glucosyl moiety. Similarly, maltose, isomaltose, and maltitol, when exposed to
      these conditions, are phosphorylated regiospecifically at O-6 of their non
      reducing glucose portion. The structures of these novel compounds have been
      established unequivocally by enzymatic analysis, acid hydrolysis, FAB negative
      ion spectrometry, and 1H and 13C NMR spectroscopy. In cells of K. pneumoniae,
      hydrolysis of sucrose 6-phosphate is catalyzed by sucrose 6-phosphate hydrolase
      from Family 32 of the glycosylhydrolase superfamily. The five 6'-O-phosphorylated
      alpha-D-glucosyl-fructoses are hydrolyzed by an inducible (approximately 49-50
      Kda) phospho-alpha-glucosidase from Family 4 of the glycosylhydrolase
      superfamily.

PMID- 11322730
TI  - Structure of epiglucan, a highly side-chain/branched (1 --> 3;1 --> 6)-beta
      glucan from the micro fungus Epicoccum nigrum Ehrenb. ex Schlecht.
AB  - The extracellular fungal polysaccharide, epiglucan, synthesised by Epicoccum
      nigrum is a side-chain/branched (1 --> 3;1 --> 6)-D-beta-glucan. Methylation
      analysis, 13C DEPT NMR and specific enzymic digestion data show slight variation
      in branching frequency among the epiglucans from the three strains examined. The
      (1 --> 3)-beta-linked backbone has (1 --> 6)-beta-linked branches at frequencies
      greater than the homologous glucans, scleroglucan and schizophyllan, from
      Sclerotium spp. and Schizophyllum commune, respectively. The structural analyses
      do not allow a distinction to be made between structures I and II. [structures:
      see text] Epiglucan displays non-Newtonian shear thinning rheological properties,
      typical of these glucans.

PMID- 11322731
TI  - Structure of the exopolysaccharide produced by Streptococcus thermophilus S3.
AB  - The exopolysaccharide of Streptococcus thermophilus S3, produced in skimmed milk,
      is composed of D-galactose and L-rhamnose in a molar ratio of 2:1. The
      polysaccharide contains 0.4 equiv of O-acetyl groups per repeating unit. Linkage
      analysis and 1D/2D NMR (1H and 13C) studies on native and O-deacetylated EPS
      together with nanoES-CID tandem mass spectrometry studies on oligosaccharides
      generated by a periodate oxidation protocol, show the polysaccharide to have the
      following structure: [structure: see text].

PMID- 11322732
TI  - Structure of the extracellular polysaccharide produced by Lactobacillus
      delbrueckii subsp. bulgaricus 291.
AB  - The lactic acid bacterium Lactobacillus delbrueckii subsp. bulgaricus 291, when
      grown in skimmed milk, produced 80 mg/L exopolysaccharide with an average
      molecular mass of 1.4 x 10(3) kDa. Monosaccharide analysis, methylation analysis,
      MS, and 1D/2D NMR (1H and 13C) studies performed on the native polysaccharide,
      and on oligosaccharides obtained from a mild acid hydrolysate of the native
      polysaccharide, showed the polysaccharide to consist of branched pentasaccharide
      repeating units with the following structure: [structure: see text].

PMID- 11322733
TI  - Structure of the O-specific polysaccharide of Proteus vulgaris O4 containing a
      new component of bacterial polysaccharides, 4,6-dideoxy-4.
AB  - A high-molecular-mass O-specific polysaccharide was obtained by mild acid
      degradation of Proteus vulgaris O4 lipopolysaccharide followed by GPC. The
      polysaccharide was studied by chemical methods along with 1H and 13C NMR
      spectroscopy, including two-dimensional COSY, TOCSY, NOESY, H-detected 1H,13C
      HMQC, and 1H,13C HMBC experiments. Solvolysis of the polysaccharide with
      trifluoromethanesulfonic (triflic) acid resulted in a GlcpA-(1 --> 3)-GlcNAc
      disaccharide and a novel amino sugar derivative, 4,6-dideoxy-4-[N-[(R)-3
      hydroxybutyryl]-L-alanyl]amino-D-glucose [Qui4N(HbAla)]. On the basis of the data
      obtained, the following structure of the tetrasaccharide repeating unit of the O
      specific polysaccharide was established: --> 4)-beta-D-GlcpA-(1 --> 3)-beta-D
      GlcpNAc-(1 --> 2)-beta-D-Quip4N(HbAla)-(1 --> 3)-alpha-D-Galp-(1 -->. This
      structure is unique among the O-specific polysaccharides, which is in accordance
      with classification of the strain studied in a separate Proteus serogroup.

PMID- 11322734
TI  - Synthesis and characterisation of dextran and pullulan sulphate.
AB  - Dextrans and pullulans of different molar masses in the range of 10(4)-10(5)
      g/mol were sulphated via a SO3-pyridine complex. The degree of substitution
      achieved was DS = 2.4 and DS = 1.4 for dextran sulphate and DS = 2.0 and DS = 1.4
      for pullulan sulphate, respectively. Confirmation of sulphation was given by FTIR
      spectroscopy. Asymmetrical S=O and symmetrical C-O-S stretching vibrations were
      detected at 1260 and 820 cm(-1). Reactivity of the polysaccharide C-atoms was
      determined by 13C NMR spectroscopy: For dextran this was C-3 > C-2 > C-4, while
      for pullulan it was C-6 > C-3 > C-2 > C-4.

PMID- 11322735
TI  - Transition metals and carbohydrates: the methyl-4,6-O-benzylidene-2,3-diazo-2,3
      dideoxy-alpha-D-mannopyranoside skeleton as building block for new chiral
      nitrogen chelates.
AB  - This paper describes a straightforward strategy for the synthesis of new nitrogen
      chelates by employing the chirality of readily available sugars. Thus, diimino
      and diamino ligands can be attained easily by using the methyl-4,6-O-benzylidene
      2,3-diazo-2,3-dideoxy-alpha-D-mannopyranoside skeleton. The coordinating ability
      of one ligand has also been assessed by preparing a square-planar palladium
      complex [PdCl2(N,N-chelate)].

PMID- 11322736
TI  - Structure of the O-specific polysaccharide of Proteus mirabilis O16 containing
      ethanolamine phosphate and ribitol phosphate.
AB  - The O-specific polysaccharide of Proteus mirabilis O16 was studied by 1H and 13C
      NMR spectroscopy, including 2D COSY, TOCSY, NOESY, H-detected 1H,13C HMQC, HMQC
      TOCSY, and 1H,31P HMQC experiments, along with chemical methods. The
      polysaccharide was found to be a ribitol teichoic acid-like polymer having the
      following structure [structure: see text].

PMID- 11322737
TI  - Structure of a D-glycero -D-manno-heptan from the lipopolysaccharide of
      Helicobacter pylori.
AB  - A lipopolysaccharide (LPS) was isolated by hot phenol-water extraction from
      Helicobacter pylori strain D4 and found to contain no fucosylated poly-N
      acetyllactosamine chain typical of most H. pylori strains studied but a
      homopolymer of D-glycero-D-manno-heptose (DD-Hep). The heptan attached to a core
      oligosaccharide was released by mild acid degradation of the LPS, and the
      following structure of the trisaccharide-repeating unit was established by
      chemical methods and 1H and 13C NMR spectroscopy: --> 2)-D-alpha-D-Hepp-(1 --> 3)
      D-alpha-D-Hepp-(1 --> 3)-D-alpha-D-Hepp-(1 -->. 1H NMR spectroscopy performed on
      small amounts of the intact LPS revealed the presence of the same polysaccharide
      in LPS of H. pylori strains D2 and D5, but not strain D10.

PMID- 11322738
TI  - Complications of SSRI treatment.

PMID- 11322739
TI  - A case of adolescent body dysmorphic disorder treated with fluvoxamine.

PMID- 11322740
TI  - Can methylphenidate facilitate sleep in children with attention deficit
      hyperactivity disorder?

PMID- 11322741
TI  - Early methylphenidate administration to young rats causes a persistent reduction
      in the density of striatal dopamine transporters.
AB  - Methylphenidate is widely and effectively used for the treatment of attention
      deficit hyperactivity disorder during early childhood and adolescence, but until
      now possible effects of this treatment on brain development and the maturation of
      monoaminergic systems have not been investigated systematically. This
      experimental animal study describes the effects of methylphenidate administration
      (2 mg/kg/day) for 2 weeks to very young (prepubertal) and somewhat older
      (postpubertal) rats on the densities of dopamine, serotonin, and norepinephrine
      transporters in the striatum and in the midbrain. As shown by ligand-binding
      assays, the K(D) values of all three transporters were unaffected by this
      treatment. No alterations were found for the Bmax values of [3H]-paroxetine and
      [3H]-nisoxetine binding, but the density of dopamine transporters (Bmax values of
      [3H]-GBR binding) in the striatum (but not in the midbrain) was significantly
      reduced after early methylphenidate administration (by 25% at day 45), and this
      decline reached almost 50% at adulthood (day 70), that is, long after termination
      of the treatment. This is the first empirical demonstration of long-lasting
      changes in the development of the central dopaminergic system caused by the
      administration of methylphenidate during early juvenile life.

PMID- 11322742
TI  - Long-term effects of stimulant medications on the brain: possible relevance to
      the treatment of attention deficit hyperactivity disorder.
AB  - In spite of extensive data supporting the short-term efficacy and safety of
      stimulant medications in the treatment of children with attention deficit
      hyperactivity disorder (ADHD), only limited information is available on the long
      term effects of these drugs. On one hand, it is unclear whether treatment of ADHD
      with amphetamine-like stimulant medications for extended periods of time during
      child development can carry negative consequences, as manifested by an increase
      in use of illicit drugs, higher incidence of mania, psychosis, or other
      manifestations of psychopathology. On the other hand, it is not known whether the
      beneficial effects of stimulants extend beyond acute symptomatic relief and
      affect important outcome variables, such as later psychopathology, educational
      achievement, antisocial behavior, and social or occupational status. Data from
      naturalistic follow-up of clinical samples are limited by lack of appropriate
      controls and self-selection biases that are difficult to determine and control.
      These studies have reached conflicting conclusions, although most of them found
      no lasting negative effects of chronic stimulant treatment. Studies in animals,
      mainly in rodents, indicate that repeated exposure to stimulants leads to
      behavioral sensitization to the psychomotor effects of these medications.
      Extrapolation of these data to therapeutic use in humans is difficult given
      interspecies differences and the relatively high doses and parenteral route of
      administration usually employed in animals. This report is based on the
      proceedings of a workshop organized by the National Institute of Mental Health in
      December 1999 to discuss possible research approaches to studying the long-term
      effects of stimulants in children with ADHD. Both clinical and basic neuroscience
      data are reviewed, and opportunities for future research are highlighted.

PMID- 11322743
TI  - Retrospective comparison of Adderall and methylphenidate in the treatment of
      attention deficit hyperactivity disorder.
AB  - Methylphenidate is the most frequently prescribed stimulant medication for the
      treatment of attention deficit hyperactivity disorder (ADHD). However, the short
      duration of action of methylphenidate requires that patients take multiple daily
      doses for optimal efficacy. Recent studies suggest that Adderall, a
      psychostimulant indicated for the treatment of ADHD, may provide an efficacious,
      less frequently dosed alternative to methylphenidate. This retrospective review
      compares the efficacy, safety, dosing frequency, and medication switch rates of
      Adderall with methylphenidate in children and adolescents with ADHD treated in a
      private, outpatient psychiatric clinic. Of the evaluable patients, 54 received
      Adderall, and 75 received methylphenidate. No statistically significant
      differences were noted between Adderall and methylphenidate in efficacy or safety
      parameters. Fewer patients receiving Adderall required twice daily, thrice daily,
      or in-school dosing than those receiving methylphenidate (p < 0.001). During the
      initial 6-month treatment period, patients treated with Adderall were less likely
      to switch medications than those receiving methylphenidate (p = 0.0002). In this
      analysis, Adderall and methylphenidate provided comparable efficacy and safety in
      children and adolescents with ADHD. The use of Adderall allowed patients to
      extend their dosing interval and reduced the need for in-school dosing, a measure
      that may substantially influence compliance.

PMID- 11322744
TI  - Variations in pharmacotherapy for attention deficit hyperactivity disorder in
      managed care.
AB  - The purpose of this study was to identify the patterns of pharmacotherapy in the
      treatment of children diagnosed with attention deficit hyperactivity disorder
      (ADHD) in a large, non-profit, group-model managed care organization from January
      1997 through July 1998. We sought to determine whether children with
      uncomplicated ADHD use different drug therapies when compared to children with
      ADHD and psychiatric comorbidity. We also examined the relationships between the
      use of specialty mental health services and the use of various psychotropic
      medications for treatment of ADHD. We found that children with ADHD and
      psychiatric comorbidity were less likely to use psychostimulants (odds ratio [OR]
      = 0.71, 95% confidence interval [CI] = 0.55-0.93, p = 0.01) but more likely to
      use antidepressants (OR = 2.74, 95% CI = 1.95-3.86, p < 0.01), alpha adrenergic
      agonists (OR = 2.63, 95% CI = 1.93-3.57, p < 0.01), and other psychotropic
      medications (OR = 2.40, 95% CI = 1.27-4.50, p < 0.01) than children with
      uncomplicated ADHD (who were more likely to use stimulants only). Additionally,
      children with psychiatric comorbidity were more likely to use multiple
      psychotropic drugs (p < 0.01). The results of this study indicate that children
      with potentially more complex mental health needs are being treated with more
      varied drug therapy and/or specialty mental health care services.

PMID- 11322745
TI  - Risperidone in the treatment of behavioral disturbances in children and
      adolescents with borderline intellectual functioning: a double-blind, placebo
      controlled pilot trial.
AB  - Risperidone, an antipsychotic agent with combined serotonin (5-HT2A) and dopamine
      (D2) receptor-blocking properties, is associated with fewer extrapyramidal side
      effects in adults than conventional neuroleptics. Approved in 1993 for the
      treatment of schizophrenia, recent studies have highlighted its potential in
      other conditions, such as the management of behavioral disturbances. This phase
      II, double-blind, placebo-controlled study evaluated the efficacy and
      tolerability of risperidone in the treatment of persistent behavioral
      disturbances in children with borderline intellectual functioning. Thirteen
      patients (6-14 years) with low IQ (66-85) were enrolled in and completed the 4
      week study. Risperidone, in daily doses of > or = 0.01 mg/kg (mean dose at
      treatment endpoint = 0.05 mg/kg; mean total dose = 1.2 mg/day), was significantly
      more effective than placebo in improving Aberrant Behavioral Checklist (ABC)
      symptom cluster scores for irritation (p < 0.05) and hyperactivity (p < 0.01),
      Clinical Global Impression score (p < 0.05), the Visual Analogue Scale score for
      individual target symptom (p < 0.001), and Personal Assessment Checklist scores
      for social relationships (p < 0.05) and occupational attitudes (p < 0.05). In
      addition, the improvement in total ABC score in the risperidone-treated group was
      clinically relevant (65% improvement vs. baseline), whereas the placebo-treated
      patients only improved 7% versus baseline. There was no difference between
      risperidone- and placebo-treated groups with respect to the occurrence of
      extrapyramidal side effects, and risperidone was well tolerated. In conclusion,
      short-term risperidone treatment was well tolerated and significantly more
      effective than placebo in controlling behavioral disturbances in children with
      low IQ.

PMID- 11322746
TI  - Tolerability of oral loading of divalproex sodium in child psychiatry inpatients.
AB  - OBJECTIVE: To determine a well-tolerated oral load of divalproex sodium that
      quickly and reliably achieves therapeutic drug levels in child psychiatry
      inpatients. METHODS: A retrospective chart review revealed that during a 6-month
      period, divalproex sodium therapy was initiated in 16 male inpatients (ages 5-14
      years). The patients were divided into two groups based on the initial dosing
      regimen. The first group received approximately 15 mg/kg/day based on actual
      weight, and the second group received approximately 15 mg/kg/day based on an
      adjusted ideal body weight (IBW). Weight was adjusted in these patients according
      to the following formula: IBW + 40% (Observed Weight - IBW). A trough blood level
      was obtained on day 5 of therapy. RESULTS: Initial drug levels ranged from 46-146
      ug/mL (mean = 90.6), of which 13 of 16 (81.3%) were considered within therapeutic
      range (50-120 ug/mL). Eight of 16 patients (50%) had reported side effects,
      including sedation and gastrointestinal upset. The majority of these side effects
      occurred in patients with drug levels > or = 90 ug/mL and were noted to improve
      with 1-2 days of therapy +/- dosage adjustment. Overweight patients (> or = 15%
      above IBW) who received the unadjusted 15 mg/kg oral load had significantly
      higher drug levels than their normal weight counterparts and overweight children
      who received weight-adjusted dosing (p < 0.003). CONCLUSION: A 15 mg/kg/day oral
      load of divalproex sodium resulted in therapeutic drug levels on day 5 of
      treatment and is well tolerated in normal weight children. Overweight children
      are significantly more likely to experience supratherapeutic drug levels on this
      regimen, which may affect tolerability. Overweight children appear to benefit
      from weight-adjusted oral loading.

PMID- 11322747
TI  - Pediatric psychotropic medication compliance: a literature review and research
      based suggestions for improving treatment compliance.
AB  - Without good compliance the best psychiatric treatment is ineffective. This
      article reviews what is known or can be inferred about compliance with
      psychiatric medications in the pediatric population. The review includes
      discussions of assessment techniques, risk and protective factors, the relevant
      research literature, and research-based practical techniques to improve
      compliance. A Medline search surveying the years from 1966 to August 2000 yielded
      only seven peer-reviewed papers reporting on compliance with pediatric
      psychopharmacology. All seven studies looked at stimulant compliance among
      children with attention deficit hyperactivity disorder. Reported levels of
      compliance range from 56% to 75%. These rates, although low, are likely to be
      overestimates of actual compliance. We review two related areas of research for
      which there are small but significant bodies of knowledge: pharmacological
      compliance studies among adult psychiatric populations and pediatric medical
      populations. This literature supports the idea that medication compliance is a
      significant obstacle to the effective treatment of patients. Because compliance
      rates are lower for children as compared to adults and psychiatric patients as
      compared to medical patients, we suspect that children with psychiatric illness
      may be at great risk for poor medication compliance. Fortunately, the research
      literature demonstrates several simple techniques that clinicians can use to
      improve medication compliance among their patients. The treatment alliance;
      education; and medication duration, dosing, palatability, and cost can all be
      tailored to improve medication compliance.

PMID- 11322748
TI  - Transcranial magnetic stimulation in young persons: a review of known cases.
AB  - There are no published data about transcranial magnetic stimulation (TMS) as a
      treatment for psychiatric disorders in young persons. The aim of this article is
      to collate available information about TMS in this population. Information was
      sought, by placing a message on the TMS Listserver, from investigators who had
      used TMS in patients 18 years of age or younger. Only one group reported
      experience in this area; it had treated seven patients, ages 16-18 years. Three
      patients had unipolar depression, three had schizophrenia, and one had bipolar
      disorder. Five of the seven patients had improved by the conclusion of the TMS
      course. Adverse events were reported in one patient. Further studies are needed
      first to investigate systematically the safety of TMS in children and adolescents
      and second to examine its potential therapeutic effects in this population.

PMID- 11322749
TI  - A revised anchored version of the BPRS-C for childhood psychiatric disorders.
AB  - The Brief Psychiatric Rating Scale for Children (BPRS-C) is increasingly used as
      an outcome measure in research, managed care, and public sector child/adolescent
      clinical settings. The BPRS-C was developed to provide a descriptive profile of
      symptoms applicable to a broad range of child and adolescent psychiatric
      disorders. Its use frequently includes trained and untrained clinician raters
      with differing degrees of experience and training in child and adolescent
      disorders. Unfortunately, this latter approach leads to a large amount of
      variability in scores and consequently reduces its overall reliability. This
      study reports on a revised BPRS-C with the addition of clinical descriptive
      anchors designed to improve reliability and validity for both trained and
      untrained raters. A sample of 4,733 children and adolescents seen in 10 public
      sector facilities was administered the BPRS-C along with other standard clinical
      measures (Child Behavior Checklist and Global Assessment of Functioning).
      Additional reliability data were gathered in a University Medical Center child
      and adolescent research site with both trained and untrained raters. The data
      indicated improvement in overall reliability and validity scores, good internal
      consistency, and improved factor scores. The addition of an overall total
      severity score may prove to be a useful outcome measure for assessment of
      treatment response.

PMID- 11322750
TI  - Effects of race on psychiatric diagnosis of hospitalized adolescents: a
      retrospective chart review.
AB  - BACKGROUND: Several studies have reported that patient ethnicity influences
      psychiatric diagnosis, although this has only been examined in adolescents in two
      prior studies. One study was based on an outpatient sample and the other was a
      retrospective study involving a relatively small sample of inpatients. We
      hypothesized that, as reported in adults, African American adolescents would be
      diagnosed with schizophrenic spectrum disorders more frequently than Caucasians,
      and Caucasians correspondingly would receive more affective disorders diagnoses.
      METHODS: We retrospectively examined the charts of all adolescents (ages 12-18
      years) admitted to the Adolescent Psychiatry Unit at Cincinnati Children's
      Hospital Medical Center (n = 1,001) between July 1995 and June 1998 for
      demographic information and discharge diagnoses. We used insurance status as a
      proxy for socioeconomic status. RESULTS: African American males were more
      commonly diagnosed with schizophrenic spectrum disorders than were African
      American women, Caucasian women, and Caucasian men. There were significantly more
      African Americans diagnosed with conduct disorder than Caucasians. In contrast,
      Caucasians were diagnosed with alcohol use disorders and major depression more
      often. CONCLUSIONS: Patient race and sex may influence clinical psychiatric
      diagnoses of hospitalized adolescents. Further investigations using structured
      interviews are necessary to determine whether the disparity in clinical diagnosis
      is secondary to actual gender and racial differences in the rates of illnesses in
      hospitalized adolescents or due to other factors that may contribute to
      diagnostic practices.

PMID- 11322751
TI  - Revisiting emerging infectious diseases: the unfinished agenda.
AB  - Infectious diseases present a formidable threat to the world today. Not only are
      new infectious diseases emerging, but those presumed to be contained or
      eradicated are re-emerging. Developing nations, with the least resources to
      respond, bear the greatest burden of this threat. However, with the potential to
      spread rapidly and ubiquitously, infectious diseases present a significant risk
      to the health and development of all nations. No country or population is immune,
      and geographic and political barriers offer little protection. Many factors
      facilitate the spread of infectious diseases, including globalization of travel
      and trade, weakening of national and international public health infrastructure,
      deterioration of socioeconomic conditions, and heightened political and civil
      strife in some developing nations. These conditions render populations more
      vulnerable to infections and provide an environment conducive to the transmission
      of infectious diseases. Compounding these risk factors is the emergence of
      another threat: antimicrobial resistance. Antimicrobial drugs are rapidly losing
      their effectiveness because of their misuse. As a result, the global health
      community is confronted with the daunting task of combating more offenders with
      fewer defenses.

PMID- 11322752
TI  - The socio-economic and cultural impediments to well-being along the US-Mexico
      border.
AB  - Among all of the underdeveloped and developing countries of the world, Mexico is
      the only nation that shares its borders with the United States. This unique link
      between the two nations has created one of the most multifaceted clusters in the
      world. Moreover, this relationship has sketched out the direction and the role of
      health services and economic development of the two countries. The cultural
      infrastructure of the region and the political force of this association affect
      and contribute to the development of the economies and to the outcomes of public
      health programs and initiatives on each side of the border. Culture as a barrier
      for integration faces many challenges. The disparities in terms of access to and
      utilization of health services that are observed along the border are enormous.
      Sometimes, such disparities exist between people from the same culture, same
      identical ethnic group, from the same racial background and in many cases from
      the same family. Lack of language skills, inadequate education and a poor
      understanding of values are not the principal impediments to well being. Instead,
      political agendas and a non-global commitment to health care are the causes for
      such discrepancies. The economy of the region possesses unusual financial
      characteristics. The Maquila industry with its cheap labor practices and the
      North American free Trade Agreement (NAFTA's) two-way crossing of billions of
      dollars contribute to such characteristics. In addition, well-known drug
      smuggling activities and the daily crossing of thousands of documented and
      undocumented people contribute to the unusual economic characteristics of this
      area. The health care development and the economic growth of both countries
      depend on mutual efforts. Each nation can benefit if these efforts are directed
      at the development of binational partnerships, the enhancement of basic services
      in the region and by providing trans-boundary health coverage for all residents
      of the region regardless of linguistic, economic and/or migratory status.

PMID- 11322753
TI  - Assessing community health among indigenous populations in Ecuador with a
      participatory approach: implications for health reform.
AB  - Health reform is an important movement in countries throughout the region of the
      Americas, which could profoundly influence how basic health services are provided
      and who receives them. Goals of health sector reform include to improve quality,
      correct inefficiencies, and reduce inequities in current systems. The latter may
      be especially important in countries with indigenous populations, which are
      thought to suffer from excess mortality and morbidity related to poverty. The
      purpose of this paper is to report the results of a community health assessment
      conducted in 26 indigenous communities in the Province of Cotopaxi in rural
      Ecuador. It is hoped that this information will inform the health reform movement
      by adding to the current understanding of the health and socioeconomic situation
      of indigenous populations in the region while emphasizing a participatory
      approach toward understanding the social forces impacting upon health. This
      approach may serve as a model for empowering people through collective action.
      Recommended health reform strategies include: 1) Develop a comprehensive plan for
      health improvement in conjunction with stakeholders in the general population,
      including representatives of minority groups; 2) Conduct research on the
      appropriate mix between traditional medicine, primary health care strategies, and
      high technology medical services in relation to the needs of the general
      population; 3) Train local health personnel and traditional healers in primary
      health care techniques; 4) Improve access to secondary and tertiary health
      services for indigenous populations in times of emergency; and 5) Advocate for
      intersectoral collaboration among government institutions as well as non
      governmental organizations and the private sector.

PMID- 11322754
TI  - Establishing an employee baseline purified protein derivative status in the
      division of immigration health Service Processing Centers.
AB  - While the incidence of reportable tuberculosis in United States born persons
      declined, the number of cases among foreign-born persons increased by 6 percent
      in 1998. The Immigration and Naturalization Service (INS) processes about 95,000
      undocumented aliens annually from countries with a high prevalence of
      tuberculosis. An effort was made to establish a baseline Purified Protein
      Derivative (PPD) status of employees of the Division of Immigration Health (DIH)
      and INS, Services Processing Centers (SPC). This was achieved through a special
      operation (project) of a one time, two-step, mass PPD testing of all SPC
      employees on all eleven sites in the United States and Puerto Rico. A reading of
      > 10mm was considered positive. The operation was optional and open to all SPC
      employees. Exclusion criteria for the study included a history of PPD skin
      testing within six months of the operation, past history of positive PPD test and
      past history of tuberculosis. Preliminary results from El Paso SPC, Texas, which
      is the largest SPC, showed that of the 148 employees which were tested (67
      percent of all employees), 17 (11 percent) were PPD positive. Security officers
      constituted 100 percent of all positive cases. Eighty-one percent of the
      employees at El Paso are security officers, eighty-seven percent of whom
      participated in the study. Only 20 (23 percent) of administrative staff
      participated in the study. Results from El Paso are suggestive of differences in
      the pattern PPD positivity among SPC employees. The complete results of the study
      should provide sound evidence for formulating appropriate policies for
      establishing an effective employee tuberculosis prevention and surveillance
      program in the Service Processing Centers.

PMID- 11322755
TI  - From international health to global health.

PMID- 11322756
TI  - Globalization, socioeconomic restructuring, and community health.
AB  - New trends in global public health have social, economic, and political
      underpinnings that can be found in three 20th century revolutions: globalization,
      a new epidemiological transition, and an historical shift in patterns of
      production and consumption throughout the world. Globalization is more than the
      internationalization of commerce and manufacture; it represents a new development
      paradigm that creates new links among corporations, international organizations,
      governments, communities, and families. Social and economic restructuring is
      reflected in the emerging health profile in underdeveloped countries, including
      those in Latin America. This emerging profile defies simple categorization,
      however; while the prevalence of cardiovascular disease and cancer has increased,
      the traditional diseases (infectious and respiratory disease) are still the
      leading cause of death. At the same time, industrialized countries are
      experiencing the re-emergence of those same traditional diseases. These apparent
      anomalies can be understood by examining class structures within and among
      countries and by linking health outcomes at the local level to new patterns of
      production and consumption in the global system.

PMID- 11322757
TI  - The health-development link: travel as a public health issue.
AB  - The process of globalization has rendered societies interdependent on one another
      and has fostered the movement of people, goods and ideas at unprecedented speed
      and volume. Global travel has grown from 25 million in 1950 to 500 million in
      1993, and estimations by 2010 reach 1 billion. The increased intensity and
      quantity of travel has resulted in greater vulnerability to the domino-type
      spread of old, new and re-emerging infectious diseases. Travelers and local
      populations are also vulnerable to death and disability due to accidents,
      violence and injuries, chronic diseases such as those due to substance abuse
      (tobacco, alcohol and others), and to undesirable behaviors such as those related
      to sex-tourism. This article argues that tourism, understood as any type of
      travel, is one of the most important sectors of the economy in many countries
      and, therefore, can contribute to community and national development. It also
      asserts that travel, as a factor in the spread of disease, lies in the realm of
      public health inquiry. It calls for greater collaboration between the tourism
      travel industry and community, national and global leaders to promote and enforce
      "responsible tourism."

PMID- 11322758
TI  - Mapping a heparin binding site on ErbB-3 epidermal growth factor receptor.
AB  - Signaling via the ErbB-family of receptors plays an important role in mammalian
      development and oncogenesis. Here we show that the ErbB-3 receptor, but not other
      members of this receptor family, binds to immobilized heparin and can be
      dissociated only at a high ionic strength comparable to that required for
      fibroblast growth factor receptors. Competition-binding analysis suggests that
      this interaction is specific and requires highly sulfated species of heparan
      sulfate. Primary sequence analysis of ErbB-3 identified a basic amino acid
      cluster (466)KHNRPRR(472) localized to the proximal, cysteine-rich extracellular
      ligand binding domain of the receptor, with charge density and distribution
      compatible with, but different to, known linear heparin binding motifs. Site
      directed mutagenesis, replacing this sequence with the corresponding residues
      from ErbB-1, resulted in complete loss of heparin binding activity of the
      chimeric receptor. Finally, antibodies directed to the putative heparin binding
      peptide, efficiently bind the native receptor suggesting a novel target for
      blocking heparin mediated ErbB-3 interactions.

PMID- 11322759
TI  - Time-dependent effects of a high-energy-yielding diet on the regulation of
      specific white adipose tissue genes.
AB  - White adipose tissue development is regulated by many factors, including the
      energy content of food and the genetic background. Nevertheless, little is known
      about possible differential effects of high-fat palatable diets when fed for
      short or long-time periods. Thus, the expression of certain genes involved with
      lipid metabolism (peroxisome proliferator-activated receptor gamma, PPARgamma2;
      retinoic receptors; fatty acid binding protein, aP2 and uncoupling proteins, UCP)
      may be affected by those dietary manipulations (high-energy-yielding diet and
      time duration of feeding). High-fat feeding for 8 days decreased mRNA UCP3 levels
      compared to control fed animals, while feeding for 30 days increased them over
      controls. Similar findings occurred for PPARgamma2 and aP2. Furthermore,
      statistically significant associations were found among PPARgamma2, aP2 and UCP3
      mRNA levels. These data suggest a physiological time-dependent response seeking
      to prevent excessive fat deposition when animals are fed for short-term with a
      high amount of dietary fat, which was followed by an adaptive period to the high
      energy content of diet throughout a coregulation among certain lipid metabolism
      related genes: PPARgamma2, aP2, UCP3.

PMID- 11322760
TI  - Genetic imbalances in preleukemic thymuses.
AB  - To understand the molecular mechanisms involved in preleukemia, the suppression
      subtractive hybridization method was used in a murine radiation-induced thymic
      lymphoma model. Seventeen mRNAs overexpressed in preleukemic thymuses were
      identified: mouse laminin binding protein (p40/37LBP), E25 protein, Rattus
      norvegicus clone BB.1.4.1, profilin, poly(A) binding protein (PABP), mouse high
      mobility group protein 1, topoisomerase I, clusterin, proteasome RC1 subunit, rat
      prostatein C3 and C1 subunits; two ESTs and four unknown genes. The
      overexpression of PABP, clusterin, profilin, and the p40/37LBP mRNAs was
      confirmed in preleukemic thymuses and can be related to some cellular events
      observed during the preleukemic period, i.e., alterations of cell cycle and
      apoptosis properties. The p40/37LBP and 67-kDa laminin receptor proteins were
      upregulated during the preleukemic period. The data suggest that additional
      studies on p40/37LBP and 67-kDa laminin receptor regulation are required to
      evaluate their potential role in the lymphoma prevention by TNF-alpha and IFN
      gamma.

PMID- 11322762
TI  - Reduced adhesion of monocyte-derived macrophages from CD36-deficient patients to
      type I collagen.
AB  - CD36 is an 88-kDa glycoprotein expressed on platelets and monocyte/macrophages
      (Mphi). CD36 is a multifunctional receptor for collagen, thrombospondin, oxidized
      low density lipoproteins (LDL), and long-chain fatty acids. The present study was
      performed to investigate whether CD36 can function as an adhesion molecule which
      is involved in mediating human macrophages (Mphi) adhesion to type I collagen in
      vitro. The Mphi of human CD36-deficient as well as normal control subjects were
      isolated and cultured on the multi-well plates coated with type I collagen, a
      natural ligand for CD36. Up to 2 h of incubation, the Mphi from CD36-deficient
      patients showed almost a approximately 55% decrease in adhesion to type I
      collagen in comparison to those from controls (P < 0.01). However, there was no
      significant difference in the adhesion thereafter. Furthermore, the addition of
      antibody against CD36 into the media of control Mphi significantly inhibited the
      adhesion by approximately 50% (P < 0.05). The addition of oxidized LDL (OxLDL)
      did not alter adhesion of Mphi from both CD36-deficient and controls. These data
      suggest that CD36 is involved in the adhesion of Mphi to type I collagen,
      especially in the early stage of adhesion.

PMID- 11322761
TI  - Insulin and contraction directly stimulate UCP2 and UCP3 mRNA expression in rat
      skeletal muscle in vitro.
AB  - To study the regulation of the mitochondrial uncoupling protein 2 and 3 (UCP2 and
      UCP3), we studied the effect of insulin and muscle contraction on UCP mRNA
      expression in rat skeletal muscle in vitro. Insulin dose-dependently increased
      skeletal muscle UCP2 and UCP3 mRNA expression in m. extensor digitorum longus
      (EDL) with maximal stimulation obtained at around 0.6-6 nM. The concentration of
      insulin giving half-maximal stimulation was 60 pM for the UCP2 and 48 pM for the
      UCP3 mRNA expression. The effect of insulin was maximal after 2 h and the effect
      was sustained during the whole study period (6 h). The insulin-induced increase
      in UCP mRNA was independent of the glucose uptake (as UCP mRNA was stimulated
      even in incubations without glucose). In addition, electrically induced
      contractions (in vitro) increased UCP2 and UCP3 mRNA expression 60-120 min after
      a single bout of contraction (for 10 min). Both the increment of UCP2 and UCP3
      mRNA were sustained throughout the study period (4 h) (153 +/- 62 and 216 +/- 71%
      above basal, P < 0.05 respectively). Finally, 5-aminoimidazole-4-carboxamid
      ribosid (AICAR), an activator of the AMP-activated protein kinase (AMPK), that is
      activated during exercise, was able to mimic the increase in UCP2 and UCP3 mRNA
      expression. In conclusion, UCP2 and UCP3 mRNA expression in skeletal muscle are
      stimulated rapidly by insulin and contraction in vitro, thus the stimulation is
      direct and not caused by changes in other hormones or metabolites. Even a brief
      bout of contraction induces an increase in UCP2 and UCP3 expression, an effect
      that could be mimicked by activation of the AMP-activated protein kinase by
      AICAR.

PMID- 11322763
TI  - Biochemical engineering of the side chain of sialic acids increases the
      biological stability of the highly sialylated cell adhesion molecule CEACAM1.
AB  - The biological half-life time of many glycoproteins is regulated via terminal
      sialic acids. In this study we determined the half-lives of two different cell
      adhesion molecules, CEACAM1 and the alpha1-integrin subunit, in PC12-cells before
      and after biochemical engineering the side chain of sialic acids by the use of N
      propanoylmannosamine. Both are transmembrane glycoproteins. While the
      immunoglobulin superfamily member CEACAM1 mediates homophilic cell-cell adhesion
      the alpha1-integrin subunit is involved in cell-matrix interactions. We found
      that the half-life of the highly sialylated CEACAM1 is increased from 26 to 40 h
      by replacement of the N-acetylneuraminic acid by the novel, engineered N
      propanoylneuraminic acids, whereas the half-life of the alpha1-integrin subunit
      remains unaffected under the same conditions. This demonstrates that biochemical
      engineering not only modulates the structure of cell surface sialic acids, but
      that biochemical engineering also influences biological stability of defined
      glycoproteins.

PMID- 11322764
TI  - Cytoprotective effect of curcumin in human proximal tubule epithelial cells
      exposed to shiga toxin.
AB  - We conducted the following experiments to determine whether curcumin, an
      antioxidant compound extracted from the spice tumeric, inhibits cell death
      induced by Shiga toxin (Stx) 1 and 2 in HK-2 cells, a human proximal tubule cell
      line. Cells were incubated for 24-48 h with Stx1 or Stx2, 0-100 ng/ml. Test media
      contained either no further additives or 10-50 microM curcumin. Exposure to Stx1
      and Stx2, 100 ng/ml, reduced cell viability to approximately 25% of control
      values after 24 h and 20 microM curcumin restored viability to nearly 75% of
      control. Cell staining confirmed that Stx1 and Stx2-induced damage in HK-2 cells
      involved a combination of apoptosis and necrosis. Thus, Stx1 caused apoptosis and
      necrosis in 12.2 +/- 2.2 and 12.7 +/- 0.9% of HK-2 cells, respectively.
      Similarly, Stx2 caused apoptosis and necrosis in 13.4 +/- 2.1 and 9.0 +/- 0.5% of
      HK-2 cells, respectively. Addition of 20 microM curcumin decreased the extent of
      apoptosis and necrosis to 2.9 +/- 2.0 and 3.8 +/- 0.2%, respectively in the
      presence of Stx1 and to 3.0 +/- 2.1 and 3.9 +/- 0.3%, respectively, for Stx2 (P <
      0.01). Stx-induced apoptosis and its inhibition by curcumin were confirmed by DNA
      gel electrophoresis and by an assay for fragmentation. The protective effect of
      curcumin against Stx1 and Stx2-induced injury to HK-2 was not related to its
      antioxidant properties. Instead, curcumin enhanced expression of heat shock
      protein 70 (HSP70) in HK-2 cells under control conditions and after exposure to
      Stx1 or Stx2. No injury was detectable after incubation of LLC-PK(1) or OK cells,
      non-human proximal tubule cell lines, with Stx1 or Stx2. Thus, curcumin inhibits
      Stx-induced apoptosis and necrosis in HK-2 cells in vitro. The cytoprotective
      effect of curcumin against Stx-induced injury in cultured human proximal tubule
      epithelial cells may be a consequence of increased expression of HSP70.

PMID- 11322765
TI  - Plasma membrane localization of palmitoylated tubulin.
AB  - PC12 pheochromocytoma cells incorporate [(3)H]palmitic acid into tubulin in a
      time- and cell-density-dependent manner. The plasma membrane-enriched fraction
      contains most of the radioactivity of the membrane pellet. While palmitoylated
      tubulin is found in both the cytoplasm and particulate fraction, the bulk of
      [(3)H]palmitic acid bound to tubulin is present in the crude membrane pellet and
      the tubulin extracted from the plasma membrane is more heavily palmitoylated than
      that extracted from endoplasmic reticulum. Detergent-extracted tubulin from
      plasma membrane is, to a large extent, polymerization competent; a substantial
      fraction, increasing as a function of labeling time, is not hydroxylamine-labile.
      The requirement for detergent extraction, the accompanying changes in tubulin
      properties and the present findings of preferential incorporation of labeled
      tubulin into plasma membranes, make it clear that direct incorporation of tubulin
      into the plasma membrane can occur.

PMID- 11322766
TI  - Human septin 3 on chromosome 22q13.2 is upregulated by neuronal differentiation.
AB  - An expression sequence tag identified in a screen for genes upregulated by
      retinoic acid induced neuronal differentiation of the human teratocarcinoma cell
      line Ntera2/D1 was found in close genomic proximity to a region of high sequence
      homology to the septin subfamily of GTPase genes. We could show that the tag
      corresponds to the 3' untranslated region of this novel gene named septin 3 and
      cloned three isoforms A (2191 bp), B (4378 bp), and C (1896 bp) from human
      Ntera2/D1 cDNA. We present the genomic localization and organization on
      chromosome 22q13.2, a chromosomal hot spot for translocations implicated in
      leukemia. Interestingly, MSF the closest paralog of septin 3 is a fusion partner
      in a therapy-related acute myeloid leukemia. Quantitative PCR confirmed the
      upregulation of the putative septin by neuronal differentiation and northern
      blotting showed only one band corresponding to sep3B with a neurospecific
      expression pattern in adult human tissues.

PMID- 11322767
TI  - Time-resolved FT-IR spectroscopic investigation of the pH-dependent proton
      transfer reactions in the E194Q mutant of bacteriorhodopsin.
AB  - The photoreaction of the E194Q mutant of bacteriorhodopsin has been investigated
      at various pH values by time-resolved step-scan Fourier-transform infrared
      difference spectroscopy employing the attenuated total reflection technique. The
      difference spectrum at pH 8.4 is comparable to the N-BR difference spectra of the
      wild type with the remarkable exception that D85 is deprotonated. Since the
      retinal configuration is not perturbed by the E194Q mutation, it is concluded
      that there is no interaction of D85 with retinal during the lifetime of the N
      state. At pH 6, a consecutive state to the O intermediate is detected in which
      D212 is transiently protonated. The comparison with wild-type bacteriorhodopsin
      reveals that protonation of D212 represents an intermediate step during proton
      transfer from D85 to the proton release group in the final stage of the reaction
      cycle. The described effects are more pronounced in the E194Q mutant than in the
      E204Q mutant demonstrating different roles of these two glutamates/glutamic acids
      at least in the final stages of the catalytic cycle of bacteriorhodopsin.

PMID- 11322769
TI  - Cholesterol enhances phospholipid binding and aggregation of annexins by their
      core domain.
AB  - Annexins are Ca(2+)-dependent phospholipid-binding proteins composed of two
      domains: A conserved core that is responsible for Ca(2+)- and phospholipid
      binding, and a variable N-terminal tail. A Ca(2+)-independent annexin 2-membrane
      association has been shown to be modulated by the presence of cholesterol in the
      membranes. Herein, the roles of the core and the N-terminal tail on the
      cholesterol-enhancement of annexin 2 membrane binding and aggregation were
      studied. The results show that (i) the cholesterol-mediated increase in membrane
      binding and in the Ca(2+) sensitivity for membrane aggregation were not modified
      by a N-terminal peptide (residues 15-26), and were conserved in mutants of the N
      terminal end (S11 and S25 substitutions); (ii) cholesterol induced an increase in
      the Ca(2+)-dependent membrane binding and aggregation of the N-terminally
      truncated protein (Delta 1-29); and (iii) annexins 5 and 6, two proteins with
      unrelated N-terminal tails and homologous core domains showed a cholesterol
      mediated enhancement of the Ca(2+)-dependent binding to membranes. These data
      indicate that the core domain is responsible for the cholesterol-mediated
      effects. A model for the cholesterol effect in membrane organisation, annexin
      binding and aggregation is discussed.

PMID- 11322768
TI  - Double-edged sword of chemosensitizer: increase of multidrug resistance protein
      (MRP) in leukemic cells by an MRP inhibitor probenecid.
AB  - The multidrug resistance protein (MRP) is a drug efflux membrane pump conferring
      multidrug resistance to tumor cells. Clinical trials have been undertaken to
      improve the effectiveness of chemotherapy by adding an MRP inhibitor to the
      treatment regimen. This study attempted not only to determine novel resistance
      mechanisms in MRP-overexpressing AML cells (AML-2/DX100) by chronic exposure to
      doxorubicin in the presence of an MRP inhibitor probenecid but also to find out
      whether probenecid could increase MRP levels. AML-2/DXPBA cultured in the
      presence of probenecid (600 microM) and doxorubicin (100 ng/ml) showed a higher
      level of the multidrug resistance (MDR) phenotype when compared to AML-2/DX100.
      AML-2/DXPBA showed increased levels of MRP compared to those of AML-2/DX100.
      Probenecid increased the MRP levels without an increase in MRP mRNA in AML-2/WT
      in both a time- and dose-dependent manner. Of the MRP inhibitors including
      probenecid, ofloxacin, erythromycin, and rifampicin used in this study, only
      probenecid showed a marked chemosensitizing effect in AML-2/DX100 but not in HL
      60/Adr, suggesting that the chemosensitizing effects of the MRP inhibitors vary
      according to the type of resistant cells. The maximum noncytotoxic concentrations
      of these MRP inhibitors increased the MRP levels to various degrees in both AML
      2/WT and HL-60/WT. However, the chemosensitizing effects of the MRP inhibitors
      were not correlated with their MRP-increasing effects. Altogether, MRP inhibitors
      such as probenecid have been shown to function as a double-edged sword,
      indicating that they are not only an effective chemosensitizer of MRP-associated
      MDR tumor cells but also an MRP activator. Therefore caution should be taken
      whenever using MRP inhibitors to reverse MRP-mediated multidrug resistance in
      clinical cancer chemotherapy as well as when used to inhibit MRP expression in
      vitro.

PMID- 11322770
TI  - 1,25-Dihydroxycholecalciferol enhances butyrate-induced p21(Waf1/Cip1)
      expression.
AB  - Butyrate, a short-chain fatty acid produced in the colon, as well as its prodrug
      tributyrin, reduce proliferation and increase differentiation of colon cancer
      cells. p21(Waf1/Cip1) and p27(Kip1) are negative regulators of cell cycle and are
      thought to have a key function in the differentiation of various cell lines. We
      studied the effects of butyrate on differentiation, VDR expression, as well as on
      p21(Waf1/Cip1) and p27(Kip1) expression in human colon cancer cells (Caco-2).
      Butyrate induced cell differentiation, which was further enhanced after addition
      of 1,25-dihydroxycholecalciferol. Synergistic effect of butyrate and
      dihydroxycholecalciferol in Caco-2 cells was due to butyrate-induced
      overexpression of VDR. While butyrate as well as dihydroxycholecalciferol
      increased p21(Waf1/Cip1) and p27(Kip1) expression, in contrast combined exposure
      of butyrate and dihydroxycholecalciferol resulted in a synergistic amplification
      of p21(Waf1/Cip1), but not of p27(Kip1) expression. These data imply that
      butyrate selectively increases p21(Waf1/Cip1) expression via upregulation of VDR
      in Caco-2 cells.

PMID- 11322772
TI  - Noncompetitive inhibition of plant protein Ser/Thr phosphatase PP7 by phosphate.
AB  - Changes in the cytoplasmic inorganic phosphate (P(i)) concentrations are an
      important cue for the plant cells to regulate their metabolism and phosphate
      homeostasis. However, phosphate sensors/receptors involved in this regulation are
      largely unknown. P(i) is a common nonspecific competitive inhibitor of
      phosphatases, usually in millimolar range. Here we report a procedure to refold
      recombinant Arabidopsis thaliana protein Ser/Thr phosphatase PP7 and demonstrate
      that PP7 is inhibited by submillimolar P(i) concentrations (IC(50) = 0.66 +/-
      0.14 mM) via a mainly noncompetitive mechanism. The results indicate that PP7 may
      possess a specific P(i)-binding site responsible for its allosteric regulation,
      and suggest a possible phosphate sensor function for this protein phosphatase.

PMID- 11322771
TI  - Evidence for FSH-dependent upregulation of SPATA2 (spermatogenesis-associated
      protein 2).
AB  - Here we report the cloning and characterization of a novel cDNA named spata 2.
      SPATA2 is the ortholog of PD1, a human testicular protein which has been
      suggested to play a role in spermatogenesis. The spata 2 sequence reveals an open
      reading frame encoding a protein of 511 amino acids. Northern blot analysis with
      rat mRNA demonstrated two distinct transcripts of 2.2 and 4.0 kb. Tagging
      recombinant SPATA2 with the green fluorescent protein (GFP) and expressing the
      chimeric polypeptide in HLtat transfected cells indicated that SPATA2 is located
      in the nucleus. RT-PCR analysis revealed that spata 2 mRNA is expressed in the
      testis and to a lesser extent in the brain while skeletal muscle and kidney
      showed a barely visible signal. The same analysis demonstrated that isolated
      Sertoli cells express spata 2 mRNA. Treating Sertoli cells with FSH in vitro
      induced remarkable changes in the steady-state level of spata 2 mRNA in a time
      dependent manner. In developing testis spata 2 transcripts were first detected 10
      days post partum and expression levels increased steadily with age. The ability
      of FSH to stimulate spata 2 mRNA expression as well as its developmental
      expression suggests that this protein might play a role in regulating
      spermatogenesis and thus, according to the Gene Nomenclature Committee, we
      propose the name SPATA2 (Spermatogenesis associated protein 2) for this protein
      (or gene).

PMID- 11322773
TI  - E2F activity is biphasically regulated by androgens in LNCaP cells.
AB  - Androgens exert a peculiar biphasic dose-dependent influence on the proliferation
      of LNCaP cells, a widely used model to study androgen effects on prostate cancer
      cells. Low concentrations of androgen stimulate proliferation, but high
      concentrations inhibit proliferation and induce strong expression of
      differentiation markers. In order to gain more insight into the molecular
      mechanisms that underlie these changes we studied the influence of a wide
      concentration range of the synthetic androgen R1881 on several cell cycle- and
      differentiation-related parameters. Low concentrations (0.1 nM), known to promote
      LNCaP cell proliferation, induce an increase of Retinoblastoma protein
      phosphorylation, accompanied by an increase of E2F-1 protein levels and E2F
      activity and by increased expression of the E2F-target gene products E2F-1 and
      cyclin A. High concentrations of R1881 (10 nM) induce strong expression of the
      differentiation marker prostate-specific antigen. Retinoblastoma protein is
      largely hypophosphorylated, resulting in low E2F activity and low concentrations
      of E2F-1 and cyclin A mRNA. Finally, there is a strong increase of p27(KIP1)
      protein, but not of p27(KIP1) mRNA. These results indicate that the biphasic dose
      response of LNCaP proliferation to androgen is closely reflected in Rb
      phosphorylation, E2F activity and p27(KIP1) protein expression.

PMID- 11322774
TI  - RGS2: regulation of expression and nuclear localization.
AB  - RGS2, a Regulators of G-protein Signaling family member, regulates signaling
      activities of G-proteins, and RGS2 itself is controlled in part by regulation of
      its expression. This investigation extended previous studies of the regulation of
      RGS2 expression by examining the effects of stress, differentiation, and
      signaling activities on RGS2 mRNA level in human neuroblastoma SH-SY5Y cells.
      Cell stress induced by heat shock rapidly and transiently increased RGS2 mRNA
      levels, whereas differentiation to a neuronal phenotype reduced basal RGS2 mRNA
      levels by 50%. RGS2 mRNA levels were increased in differentiated cells by heat
      shock, carbachol, and activation of protein kinase C. After transient
      transfection of GFP-tagged RGS2, a predominant nuclear localization was observed
      by confocal microscopy. Thus, RGS2 expression is regulated by stress and
      differentiation, as well as by second messenger signaling, and transfected GFP
      RGS2 is predominantly nuclear.

PMID- 11322775
TI  - Cell-specific properties of type V and type IX adenylyl cyclase isozymes in 293T
      cells and embryonic chick ventricular myocytes.
AB  - The cDNAs for types V and IX adenylyl cyclases were cloned from a chicken heart
      library and expressed in 293T cells (plasmid transfection) and in embryonic chick
      ventricular myocytes (adenovirus infection). Expression of type V or IX cyclases
      in 293T cells resulted in increases in basal and isoproterenol (ISO)-stimulated
      cAMP levels, whereas the expression of type V, but not type IX, cyclase increased
      forskolin (FK)-stimulated cAMP levels. Expression of type V cyclase in cardiac
      myocytes increased basal and FK-stimulated cAMP levels, variably increased ISO
      stimulated cAMP levels, and decreased the content of beta-adrenergic receptors
      (betaARs). The expression of type IX cyclase in cardiac myocytes increased basal
      and ISO-elevated cAMP levels and, surprisingly, increased the cAMP-elevating
      effect of FK. The finding that FK responses are increased in cardiac myocytes but
      not in 293T cells expressing the type IX cyclase suggests that the host cell
      influences the properties of the type IX isozyme.

PMID- 11322776
TI  - A point mutation in a cadherin gene, Cdh23, causes deafness in a novel mutant,
      Waltzer mouse niigata.
AB  - A novel mouse model for human nonsyndromic hearing loss, Waltzer niigata
      (v(ngt)), is found and subjected to positional cloning analysis. Genome-wide scan
      of 1648 backcross mice maps v(ngt) to the D10Mit258 locus near Waltzer (v).
      Recombination breakpoints are positioned on a physical map consisting of 13 BACs
      relative to the flanking markers in the vicinity of v(ngt). Allelism test done in
      parallel shows that v(ngt) and v are allelic. Sequence analysis reveals one-base
      deletion in the cDNA encoding a cadherin-related protein, Cdh23, mutation of
      which is recently reported in v mutants. The frame-shift change, producing a
      truncated protein of 51 amino acids, is ascribed to a base-substitution of G to A
      in the acceptor site of splicing junction which is predicted to cause one-base
      shift of the splicing position.

PMID- 11322777
TI  - Effect of CETP on the plasma lipoprotein profile in four strains of transgenic
      mouse.
AB  - The plasma cholesteryl ester transfer protein (CETP) plays a central role in high
      density lipoprotein (HDL) metabolism and reverse cholesterol transport. There are
      conflicting views regarding whether or not excessive CETP activity is one of the
      risk factors of atherosclerosis. To study how much effect CETP can have on the
      profiles of plasma lipoproteins in vivo, we produced four strains of transgenic
      mouse that expressed different levels of human CETP gene. We analyzed seven
      groups of mice that had different levels of CETP expression. The cholesterol
      level of HDL, chylomicron (CM) and VLDL, intermediate density lipoprotein (IDL)
      and LDL were proportionally changed in association with plasma CETP
      concentrations (2.9 +/- 0.6 to 37.4 +/- 1.7 microg/ml) in an allelic dose
      dependent manner. We further characterized one of the transgenic strains, CETP-4,
      by optimizing the experimental condition for the mouse model of atherosclerosis,
      and found that it would be useful for the development of therapeutics against
      atherosclerosis.

PMID- 11322778
TI  - Substituted beta-cyclodextrins interact with PAMAM dendrimer-DNA complexes and
      modify transfection efficiency.
AB  - The efficiency of PAMAM dendrimer-mediated DNA transfer can be improved by the
      addition of substituted beta-cyclodextrins (beta-CDs) as formulation excipients.
      In vitro CAT expression increased approximately 200-fold when dendrimer/DNA/beta
      CD formulations were applied on the surface of collagen membranes. The inclusion
      of beta-CD into the formulations resulted in particles that were smaller and more
      evenly distributed on the surface of the solid support. The average size of the
      complex formed at 50 microg/ml and at charge ratio of 1 decreased from 156 nm to
      5.8 nm and 21.2 nm in 0.025-0.1% w/vol beta-CDs. Sulfonated beta-CDs bind to
      dendrimer and in the increased concentration may displace DNA in the
      dendrimer/DNA complex. High concentrations of amphoteric beta-CD do not
      dissociate dendrimer/DNA complexes; however, they may decrease their ability to
      transfect cells. At the optimized formulations the surface-modified beta-CDs may
      enhance solid support-based transfection in vitro, through modification of
      dendrimer/DNA complex composition and improved surface distribution.

PMID- 11322779
TI  - Identification of genes upregulated in the inflamed colonic lesions of Crohn's
      disease.
AB  - To identify the molecular mechanism which primarily plays a role in the
      pathogenesis of Crohn's disease (CD) without prior hypothesis, differential
      display method was employed to detect differentially expressed genes between the
      inflamed and uninflamed colonic samples from one patient with CD. The mRNA levels
      of these genes were subsequently semi-quantitated in affected and unaffected
      tissues from six patients using reverse transcriptase polymerase chain reaction
      (RT-PCR). Six genes including long form FLICE inhibitory protein (FLIP(L)) were
      found to be consistently overexpressed in the inflamed colonic CD tissues.
      Immunohistochemical studies revealed that FLIP(L) expressing cells were lamina
      propria lymphocytes (LPLs). The present study suggested that overexpression of
      FLIP(L) in the LPLs may be involved in the pathogenesis of CD through defective
      activation-induced cell death. In addition, this study provided evidence for a
      possible role of several previously unsuspected genes in the pathogenesis of CD.

PMID- 11322780
TI  - Increased GTP-binding to dynamin II does not stimulate receptor-mediated
      endocytosis.
AB  - Regarding the molecular mechanism of dynamin in receptor-mediated endocytosis,
      GTPase activity of dynamin has been thought to have a critical role in endocytic
      vesicle internalization. However, a recent report suggested that GTP-binding to
      dynamin itself activates the dynamin to recruit molecular machinery necessary for
      endocytosis. In this study, to investigate the role of GTP binding to dynamin II,
      we generated two mutant dynamin II constructs: G38V and K44E. G38V, its GTP
      binding site might be mainly occupied by GTP caused by reduced GTPase activity,
      and K44E mutant, its GTP binding site might be vacant, caused by its decreased
      affinity for GTP and GDP. From the analysis of the ratio of GTP vs GDP bound to
      dynamin, we confirmed these properties. To test the effect of these mutant
      dynamins on endocytosis, we performed flow cytometry and confocal
      immunofluorescence analysis and found that these two mutants have inhibitory
      effect on transferrin-induced endocytosis. Whereas fluorescent transferrin was
      completely internalized in wild-type (WT) dynamin II expressing cells, no
      intracellular accumulation of fluorescent transferrin was found in the cells
      overexpressing K44E and G38V mutant. Interestingly, the amount of GTP bound to
      K44E was increased when endocytosis was induced than that bound to WT. The
      present results suggested that the GTPase activity of dynamin II is required for
      formation of endocytic vesicle and GTP-binding to dynamin II per se is not
      sufficient for stimulating endocytosis.

PMID- 11322781
TI  - Reactive oxygen species modulate angiotensin II-induced beta-myosin heavy chain
      gene expression via Ras/Raf/extracellular signal-regulated kinase pathway in
      neonatal rat cardiomyocytes.
AB  - Angiotensin II (Ang II) causes cardiomyocytes hypertrophy. Cardiac beta-myosin
      heavy chain (beta-MyHC) gene expression can be altered by Ang II. The molecular
      mechanisms are not completely known. Reactive oxygen species (ROS) are involved
      in signal transduction pathways of Ang II. However, the role of ROS on Ang II
      induced beta-MyHC gene expression remains unclear. Here we found that Ang II
      increased beta-MyHC promoter activity and it was blocked by Ang II type 1
      receptor antagonist losartan. Ang II dose-dependently increased the intracellular
      ROS. Cardiomyocytes cotransfected with a dominant negative mutant of Ras
      (RasN17), Raf-1 (Raf301), or a catalytically inactive mutant of extracellular
      signal regulated kinase (mERK2) inhibited Ang II-induced beta-MyHC promoter
      activity, indicating Ras/Raf/ERK pathway was involved. Antioxidants such as
      catalase or N-acetyl-cysteine decreased Ang II-activated ERK phosphorylation and
      inhibited Ang II-induced beta-MyHC promoter activity. These data indicate that
      Ang II increases beta-MyHC gene expression in part via the generation of ROS.

PMID- 11322782
TI  - Variation in the human ApoB signal peptide modulates ApoB17 translocation.
AB  - The functional effects of the common 27- or 24-amino-acid (aa) variants in the
      human apoB signal peptide (SP) on intracellular and secreted apoB17 were
      investigated in vitro. Only in the presence of oleate was a significant
      difference in intracellular and secreted SP27-B17 compared to SP24-B17 observed
      (P = 0.01 and P < 0.0007, respectively), although in the presence or absence of
      oleate mRNA levels from the two constructs were similar. After fractionation,
      oleate treatment enhanced microsomal SP27-B17 by 150% (P < 0.0005) with a modest
      but significant effect on SP24-B17 (32% P = 0.007). Oleate stimulated SP24-B17
      accumulation in the nonmicrosomal fraction. The data suggest that the presence of
      oleate leads to inefficient translocation of the 24-amino-acid signal peptide,
      possibly resulting in increased retrograde translocation into the cytoplasm and
      reduced intracellular and secreted levels compared to the "wildtype" 27 aa SP.
      This implies a direct role of the SP variants in the regulation of apoB
      intracellular metabolism.

PMID- 11322783
TI  - Enhanced stimulation of Akt-3/protein kinase B-gamma in human aortic smooth
      muscle cells.
AB  - Growth factor-induced activation of Akt (protein kinase B) is implicated in the
      proliferation of vascular smooth muscle cells (VSMC) in addition to antiapoptotic
      signaling. Although previous studies have documented increases in total Akt or
      Akt-1 activity in rodent VSMC, little is known about the regulation of Akt-2 or
      Akt-3 kinase activity in VSMC from any species. In the present study, reverse
      transcriptase-polymerase chain reaction revealed the expression of all three Akt
      isoforms in human aortic VSMC. In vitro kinase assays using immunoprecipitated
      Akt isoforms showed robust increases in Akt-3 activity after stimulation of human
      aortic VSMC with platelet-derived growth factor (PDGF), insulin, and insulin-like
      growth factor-1. In contrast, these growth factors produced modest and marginal
      increases in Akt-1 and Akt-2 kinase activity, respectively. Pretreatment of VSMC
      with a phosphoinositide-3kinase (PI-3K) inhibitor, LY294002, led to significant
      inhibition of growth factor(s)-induced increases in Akt-3 activity and DNA
      synthesis. The present findings provide the first direct evidence that the Akt-3
      isoform is predominantly activated in human aortic VSMC. Moreover, these data
      suggest that PI-3K-dependent activation of Akt-3 may play a major role in VSMC
      proliferation.

PMID- 11322784
TI  - Peptides encoded by exon 6 of VEGF inhibit endothelial cell biological responses
      and angiogenesis induced by VEGF.
AB  - VEGF induces pathological angiogenesis and is an important target for the
      development of novel antiangiogenic molecules. In this study, we tested synthetic
      peptides based on the sequence of VEGF(189) for their ability to inhibit VEGF
      receptor binding and biological responses. We identified 12-amino acid peptides
      derived from exon 6 that inhibited VEGF binding to HUVECs, VEGF-stimulated ERK
      activation, and prostacyclin production. These peptides inhibited VEGF-induced
      mitogenesis, migration, and VEGF-dependent survival of endothelial cells, but
      caused no increase in apoptosis in the absence of VEGF. Exon 6-encoded peptides
      also caused a marked inhibition of VEGF-induced angiogenesis in vitro. Studies of
      effects of peptides on cross-linking of VEGF to its receptors and on binding of
      VEGF to porcine aortic endothelial cells expressing either KDR or neuropilin-1
      showed that exon 6-encoded peptides effectively blocked the interaction of VEGF
      with both receptors. Exon 6-derived peptides caused release of bFGF from
      endothelial cells but inhibited bFGF-dependent ERK activation, cell proliferation
      and angiogenesis. Our findings indicate that VEGF exon 6-encoded peptides inhibit
      VEGF-induced angiogenesis, at least in part through inhibition of VEGF binding to
      KDR. In addition, exon 6-encoded peptides are also effective inhibitors of bFGF
      mediated angiogenesis.

PMID- 11322785
TI  - Osmotic regulation of ATA2 mRNA expression and amino acid transport System A
      activity.
AB  - When porcine endothelial cells were exposed to hypertonicity, both the level of
      ATA2 (amino acid transporter 2) mRNA and activity of amino acid transport System
      A increased transiently, peaking after about 6 and 9 h, respectively.
      Cycloheximide, like actinomycin D, prevented both responses, showing that an
      earlier step also involves protein synthesis. Withdrawal of hypertonicity after 6
      h increased the rate of down regulation. These findings confirm that ATA2 is a
      major isoform of System A and show that changes in the expression of ATA2 mRNA
      precede both the induction and subsequent down regulation of transport activity.

PMID- 11322786
TI  - Cross-talk between signal transducer and activator of transcription 3 and
      androgen receptor signaling in prostate carcinoma cells.
AB  - Interleukin 6 (IL-6) plays important roles in the immune system, hematopoiesis,
      as well as the growth of various tumors. Androgens are important in the
      initiation and progression of prostate cancer and their effects are mediated by
      androgen receptor (AR). Here we present a molecular mechanism for the effects of
      IL-6 on prostate cancer cells through a cross-talk between IL-6 and AR signaling
      pathways. IL-6-induced activation of signal transducer and activator of
      transcription 3 (STAT3) was augmented by AR in the presence of
      dihydrotestosterone (DHT). In addition, DHT treatment augmented endogenous STAT3
      mediated gene expression by IL-6. Conversely, DHT-induced AR activity was
      increased by IL-6, and a dominant negative form of STAT3 inhibited AR activation.
      In contrast, DHT-mediated enhancement of STAT3 activation was inhibited by
      flutamide, an AR antagonist. We provide evidence that these activities are due to
      direct physical interactions between STAT3 and AR in prostate cancer cells.

PMID- 11322787
TI  - Isolation of genomic DNA sequences that bind vitamin D receptor complexes.
AB  - Vitamin D signaling is believed to be transduced by a heterodimeric receptor
      complex that binds to specific sequences of DNA termed vitamin D response
      elements (VDREs) in the promoter regions of target genes. However, recent studies
      have suggested that considerable flexibility exists in the types of binding sites
      the vitamin D receptor (VDR) is capable of recognizing, including some that bind
      VDR homodimers. In this report, a screening method involving immunoselection and
      PCR amplification was utilized to examine genomic binding sites for the receptor.
      Four individual fragments ranging in size from ca. 250-320 bp were nominally
      isolated from the amplified pool of captured fragments for further analysis. Each
      of the four sequences was capable of forming specific, unique VDR complexes using
      recombinant human VDR (rhVDR) alone or rhVDR heteromers formed in conjunction
      with the addition of recombinant human retinoid X receptor alpha (rhRXRalpha).
      Two of these fragments exhibited significant hormone-dependent repression of
      luciferase activity when linked to a thymidine kinase driven reporter vector.
      DNaseI footprinting revealed specific binding over DR+3 or related half-site
      sequences found within both of these DNA fragments. The results from this study
      demonstrate that specific, functional binding sites for the VDR can be
      successfully isolated from genomic DNA and should aid in the discovery of genes
      regulated by the steroid hormone.

PMID- 11322788
TI  - Isolation and characterization of the genes encoding a novel oxygenase component
      of angular dioxygenase from the gram-positive dibenzofuran-degrader Terrabacter
      sp. strain DBF63.
AB  - A gram-positive bacterium Terrabacter sp. strain DBF63 is able to degrade
      dibenzofuran (DF) via initial dioxygenation by a novel angular dioxygenase. The
      dbfA1 and dbfA2 genes, which encode the large and small subunits of the
      dibenzofuran 4,4a-dioxygenase (DFDO), respectively, were isolated by a polymerase
      chain reaction-based method. DbfA1 and DbfA2 showed moderate homology to the
      large and small subunits of other ring-hydroxylating dioxygenases (less than
      40%), respectively, and some motifs such as the Fe(II) binding site and the [2Fe
      2S] cluster ligands were conserved in DbfA1. DFDO activity was confirmed in
      Escherichia coli cells containing the cloned dbfA1 and dbfA2 genes with the
      complementation of nonspecific ferredoxin and ferredoxin reductase component of
      E. coli. Under this condition, these cells exhibited angular dioxygenation of DF
      and dibenzo-p-dioxin, and monooxygenation of fluorene, but not angular
      dioxygenation of carbazole, xanthene, and phenoxathiin. Phylogenetic analysis
      revealed that DbfA1 formed a branch with recently reported large subunits of
      polycyclic aromatic hydrocarbon (PAH) dioxygenase from gram-positive bacteria but
      did not cluster with that of other angular dioxygenases, i.e., DxnA1 from
      Sphingomonas sp. strain RW1 [Armengaud, J., Happe, B., and Timmis, K. N. J.
      Bacteriol. 180, 3954-3966, 1998] and CarAa from Pseudomonas sp. strain CA10
      [Sato, S., Nam, J.-W., Kasuga, K., Nojiri, H., Yamane, H., and Omori, T. J.
      Bacteriol. 179, 4850-4858, 1997].

PMID- 11322789
TI  - A nucleus-localization-deficient mutant serves as a dominant-negative inhibitor
      of gut-enriched Kruppel-like factor function.
AB  - Cancer cells differ from normal cells in many aspects, including loss of
      differentiation and uninhibited cell proliferation. Recent studies have suggested
      that gut-enriched Kruppel-like factor (GKLF) played an important role in the
      regulation of cell growth in the colon. Studies from this laboratory have shown
      that GKLF protein predominantly expressed in the cytoplasm but not the nucleus of
      colon cancer cells, suggesting that impaired nuclear translocation of GKLF might
      contribute to cancer formation. In this report, a region containing putative
      nuclear localization signal (NLS) of GKLF (PKRGRR; amino acids 385-390) was
      investigated. Mutation of KR to WT had no effect on the inhibitory properties of
      GKLF on cyclin D1 promoter activity and [(3)H]thymidine uptake in HT-29 cells,
      whereas mutation of RR to GL abolished GKLF function completely. Additional
      mutation analyses demonstrated that Arg(390) is the most critical moiety within
      this region that mediated GKLF function and its nucleus localization.
      Cotransfection of Arg(390) mutant (RR/RS) completely inhibited wild-type GKLF
      function, and GFP-RR/RS GKLF fusion proteins failed to translocate to the
      nucleus. The results from this study demonstrate that Arg(390) confers the NLS of
      GKLF and that the nucleus-localization-deficient mutant serves as dominant
      negative inhibitor of GKLF function.

PMID- 11322790
TI  - Conserved structure and promoter sequence similarity in the mouse and human genes
      encoding the zinc finger factor BERF-1/BFCOL1/ZBP-89.
AB  - We have characterized the genomic structure of the mouse Zfp148 gene encoding
      Beta-Enolase Repressor Factor-1 (BERF-1), a Kruppel-like zinc finger protein
      involved in the transcriptional regulation of several genes, which is also termed
      ZBP-89, BFCOL1. The cloned Zfp148 gene spans 110 kb of genomic DNA encompassing
      the 5'-end region, 9 exons, 8 introns, and the 3'-untranslated region. The
      promoter region displays the typical features of a housekeeping gene: a high G+C
      content and the absence of canonical TATA and CAAT boxes consistent with the
      multiple transcription initiation sites determined by primary extension analysis.
      Computer-assisted search in the human genome database allowed us to determine
      that the same genomic structure with identical intron-exon organization is
      conserved in the human homologue ZNF 148. Functional analysis of the 5'-flanking
      sequence of the mouse gene indicated that the region from nucleotide -205 to
      +144, relative to the major transcription start site, contains cis-regulatory
      elements that promote basal expression. Such sequences and the overall promoter
      architecture are highly conserved in the human gene. Furthermore, we show that
      the complex transcription pattern of the Zfp148 gene might be due to a
      combination of alternative splicing and differential polyadenylation sites
      utilization.

PMID- 11322791
TI  - Tertiary structures of the Escherichia coli and human chromosome 21 molecules of
      DNA.
AB  - Using the NDB database, we calculated geometrical parameters that were needed to
      reproduce crystal structures of short DNA fragments in a phosphorus atom
      representation. The geometrical parameters were included in a software generating
      tertiary structures of, for example, the Escherichia coli and human chromosome 21
      molecules of DNA whose complete nucleotide sequences are deposited in the EMBL
      and related databases. Both molecules were found to be heavily folded and
      composed of domains. A more elaborate version of the present approach will make
      analysis and comparison possible of tertiary structures of genomic DNA molecules
      of various chromosomes to identify the chromosome evolutionary and functional
      relationships.

PMID- 11322792
TI  - Structural basis for triclosan and NAD binding to enoyl-ACP reductase of
      Plasmodium falciparum.
AB  - Recent discovery of type II fatty acid synthase in the malarial parasite
      Plasmodium falciparum responsible for the most debilitating form of the disease
      in humans makes it ideal as a target for the development of novel antimalarials.
      Also, the identification of the enoyl-acyl carrier protein reductase from P.
      falciparum and the demonstration of its inhibition by triclosan [5-chloro-2-(2,4
      dichlorophenoxy)phenol], a potent antibacterial compound, provide strong support
      for the above. In the studies reported here, a model of the enzyme in complex
      with triclosan and the cofactor NAD has been built by homology modeling with a
      view to understand its binding properties and to explore the potential of
      triclosan as a lead compound in designing effective antimalarial drugs. The model
      indeed provided the structural rationale for its interaction with ligands and the
      cofactor and revealed unique characteristics of its binding site which could be
      exploited for improving the specificity of the inhibitors.

PMID- 11322793
TI  - Chromium(III)-induced structural changes and self-assembly of collagen.
AB  - Rat tail tendon (RTT) collagen has been reacted with a homologous series of
      chromium(III) complexes viz., (H2O)(4)Cr(OH)(2)Cr(H2O)(4+)(4) 1 (dimer),
      Cr(3)(OH)(4)(H2O)(5+)(9) 2 (trimer), and Cr(4)(OH)(4)(O2)(H2O)(4+)(12) 3
      (tetramer), and the structural alterations brought about by these complexes have
      been investigated through atomic force microscopy (AFM) and circular dichroism
      (CD) studies. Examination of Cr(III)-treated tendons using AFM revealed changes
      in the D-periodicity of collagen, which may arise due to differences in the
      topological distribution of various Cr(III) complexes. Evidence for organisation
      of monomeric collagen into quarter staggered fibrils in the presence of Cr(III)
      dimer, 1, has been obtained. The quaternary structural changes induced by
      chromium in the protein have been correlated to the conformational changes of
      collagen in the absence of denaturation.

PMID- 11322794
TI  - Molecular genetic identification of a candidate receptor gene for sweet taste.
AB  - A cDNA clone encoding a novel member of the putative taste receptor T1R family,
      designated T1R3, was isolated from circumvallate papillae of the mouse tongue
      using degenerate primers. Reverse transcription-polymerase chain reaction
      analysis showed predominant expression of the receptor in circumvallate papillae.
      In situ hybridization analysis revealed that T1R3 was expressed in a subset of
      taste receptor cells in taste buds and that the topographic distribution of T1R3
      in various taste papillae was different from those of the other T1R members.
      Genetic mapping of T1R3 with a mouse/hamster radiation hybrid panel located the
      gene on the distal end of mouse chromosome 4 correlated with the Sac locus
      affecting sweet sensitivity of mice. Our results indicate that T1R3 may serve as
      the receptor for sweet perception in mice.

PMID- 11322795
TI  - Identification of GABA(B) receptor in rat testis and sperm.
AB  - gamma-Aminobutyric acid (GABA) can mimic and potentiate the action of
      progesterone in initiating the acrosome reaction (AR) of mammalian sperm,
      indicating that sperm contain receptors for GABA. This contention was validated
      by identifying the receptor (R) subtype, GABA(A)R, in mammalian sperm. In the
      present study a second subtype, GABA(B)R, was identified in rat testis and sperm.
      Total RNAs of rat testis and sperm were prepared and used as template to
      synthesize the respective cDNAs by the RT-PCR method. Two splice variants of the
      cDNA coding GABA(B)R1 (GABA(B)R1a and GABA(B)R1c) and GABA(B)R2 were identified.
      Extracts of rat testis, spermatogenic cells and sperm contained two proteins with
      estimated molecular sizes of 130 and 100 kDa, corresponding to GABA(B)R1a and
      GABA(B)R1c/lb, respectively, determined by Western blot using polyclonal anti
      GABA(B)R1 antibody. By an indirect immunofluorescence technique, GABA(B)R1 was
      located on the head of rat sperm. The present finding is the first direct
      demonstration that mammalian sperm contain GABA(B)R.

PMID- 11322796
TI  - A MEK inhibitor, PD98059 enhances IL-1-induced NF-kappaB activation by the
      enhanced and sustained degradation of IkappaBalpha.
AB  - Interleukin-1 (IL-1) mediates numerous host responses through rapid activation of
      nuclear factor-kappaB (NF-kappaB), but signal pathways leading to the NF-kappaB
      activation appear to be complicated and multiplex. We propose a novel regulatory
      system for NF-kappaB activation by the extracellular signal-related kinase (ERK)
      pathway. In a human glioblastoma cell line, T98G, IL-1-induced NF-kappaB
      activation was significantly augmented by the pretreatment of a specific MEK
      inhibitor, PD98059. In contrast, ectopic expression of a constitutive activated
      form of Raf (v-Raf) reduced IL-1-induced NF-kappaB activation, and this
      inhibition was completely reversed by PD98059. Interestingly, PD98059 sustained
      IL-1-induced NF-kappaB DNA binding activity by an electrophoretic mobility shift
      assay and also IkappaBalpha degradation, presumably by augmenting and sustaining
      the proteasome activation. Concomitantly, two NF-kappaB dependent genes, A20 and
      IkappaBalpha expression were prolonged with PD98059. These data suggested that
      MEK-ERK pathway exerts a regulatory effect on NF-kappaB activation, providing a
      novel insight on the role of MEK-ERK pathway.

PMID- 11322797
TI  - C terminal CYS-RICH region of mumps virus structural V protein correlates with
      block of interferon alpha and gamma signal transduction pathway through decrease
      of STAT 1-alpha.
AB  - It has been reported that interferon (IFN)-alpha/gamma signal transduction
      pathway is blocked in several cell lines persistently infected with mumps virus
      (MV) through decrease of STAT-1alpha. Expression of the MV structural V protein
      (MV-V) or C terminal CYS-RICH region of the V protein (MV-Vsp) inhibited the
      establishment of the antivirus state induced by IFN, but not by expression of the
      MV-P protein. Suppression of IFN-induced STAT-1alpha, STAT-2, and IRF-9 (p48)
      induction was also recognized in the cells transfected with expression vector of
      the MV-V (pTM-V) or MV-Vsp (pTM-Vsp) protein, even though it was in the absence
      of the other virus protein. It is supposed that the cysteine-rich domain of V
      protein (Vsp) is involved in the suppression of the IFN signal transduction
      pathway.

PMID- 11322798
TI  - Interaction of nuclear proteins with repeat sequences in the 5' flanking region
      of mouse muscle creatine kinase gene during aging.
AB  - The 5' flanking region of the mouse muscle creatine kinase (MCK) gene contains
      two repeat sequences-a mononucleotide repeat, (A)(22) (-2694 to -2673), and a
      tetranucleotide repeat, (GTTT)(8) (-2962 to -2931). We show here that these
      repeats in the mouse MCK gene bind to specific nuclear protein factors. Some of
      the factors interacting with these sequences are tissue-specific and show age
      related decrease in the binding activity. Nonspecific competitor and heterologous
      DNA probes failed to compete out the complexes showing that the interaction is
      specific to the repeat sequences. These proteins may have a role in the
      expression of the gene during aging.

PMID- 11322799
TI  - Transport of tools and mental representation: is capuchin monkey tool behaviour a
      useful model of Plio-Pleistocene hominid technology?
AB  - Capuchin monkeys display greatly developed tool-using capacities, performing
      successfully a variety of tool-tasks. Impressed by their achievements in this
      respect, some investigators have suggested that capuchin tool-using behaviour
      could be used as a model of the tool behaviour of the first hominids. The
      transport of tools, a task requiring complex cognitive capabilities, is an
      essential ingredient in the technological behaviour of the first hominids. In
      this way, to qualify as another source for modelling hominid behavioural
      evolution, capuchins had to exhibit proficiency in the transport of tools. We
      investigated this problem through experiments designed to elicit the transport of
      objects. The results showed that the monkeys were able to transport food to be
      processed with the use of tools, but failed when the tools themselves had to be
      transported. Our hypothesis is that a limited capacity for abstract
      representation, together with the lack of a regulatory system ensuring that the
      food would not be lost and consumed by another individual during the search for
      and transport of the tools, were responsible for such a failure. We conclude that
      the tool-using behaviour of capuchins presents no functional analogy with the
      tool behaviour of the Plio-Pleistocene hominids, and that capuchin monkeys are a
      very inadequate source for modelling Plio-Pleistocene hominid's technological
      behaviour.

PMID- 11322800
TI  - Direct ESR dating of a Pliocene hominin from Swartkrans.
AB  - Two fragments of a hominin tooth (Australopithecus robustus) and two bovid teeth
      from the Hanging Remnant of the Swartkrans Formation were analysed with ESR.
      Research was complicated by the fact that the samples came from a curated
      collection and their precise provenance is unknown. The environmental dose rate
      was reconstructed by a series of in situ gamma spectrometric measurements and
      elemental analyses of a range of sediment samples. U-series isotopic analyses
      indicated that each of the teeth had a significantly different uranium uptake
      history, rendering the assumptive early U-uptake and linear U-uptake models
      ineffective. ESR and U-series data were combined to calculate open system ages,
      resulting in a best estimate of 1630+/-160 ka for the Hanging Remnant. An open
      system model which provides the maximum age for given U-series and ESR
      measurements yielded an estimate of about 2100 ka. Two bovid teeth from Member 2,
      previously estimated to be between 1.0 and 2.0 Ma, yielded age estimates of
      between about 100 and 200 ka. No known geochemical processes are likely to
      explain this severe age underestimation. We conclude that these samples are of
      Middle to Upper Pleistocene age and their presence in Member 2 was either due to
      reworking or inadequate stratigraphical discrimination of these deposits.

PMID- 11322801
TI  - A new anthropoid from the latest middle Eocene of Pondaung, central Myanmar.
AB  - A new genus and species of medium-sized fossil primate, Myanmarpithecus
      yarshensis, is described from the lastest middle Eocene sediments of Pondaung,
      central Myanmar (Burma). The specimens consist of right maxillary fragments with
      P(4)-M(3)and a left mandibular corpus with C-P(3)and M(2-3). To date, three
      purported anthropoids have been discovered from the Pondaung Formation:
      Pondaungia and Amphipithecus (Amphipithecidae) and Bahinia (Eosimiidae).
      Myanmarpithecus differs from these other Pondaung primates in having cingular
      hypocones on upper molars and in lacking paraconids on M(2-3). Although
      Myanmarpithecus resembles some utahiin omomyines in superficial aspects of the
      morphology of M(2-3)(i.e., mesiodistally compressed molar trigonid and enamel
      crenulation), the morphological analysis of upper molars and lower premolars
      indicates that it is neither an omomyoid nor an adapoid but is more derived than
      fossil prosimians (such as adapoids, omomyoids, and tarsiers) and more anthropoid
      like. On the other hand, it is more primitive (prosimian-like) than early
      anthropoids from the late Eocene/early Oligocene of the Fayum, Egypt.
      Myanmarpithecus is likely to be an early, primitive anthropoid
      ("protoanthropoid").

PMID- 11322802
TI  - Stw 441/465: a new fragmentary ilium of a small-bodied Australopithecus africanus
      from Sterkfontein, South Africa.
AB  - In 1986 and 1987, a hominid left ilium fragment consisting of a spina iliaca
      anterior superior and crista iliaca was discovered during excavations at
      Sterkfontein, South Africa. Although the specimen is small it gives valuable
      hints for muscle insertions and origins at the pelvis of Australopithecus
      africanus. It indicates that the anatomy of the abdominal muscles and of the mm.
      glutei medius et minimus of A. africanus was quite different from that of the
      great apes and more similar to that of modern humans. This has major implications
      for the interpretation of the bipedalism and locomotor efficiency of the early
      South African hominids.

PMID- 11322803
TI  - Unique morphology of the human eye and its adaptive meaning: comparative studies
      on external morphology of the primate eye.
AB  - In order to clarify the morphological uniqueness of the human eye and to obtain
      cues to understanding its adaptive significance, we compared the external
      morphology of the primate eye by measuring nearly half of all extant primate
      species. The results clearly showed exceptional features of the human eye: (1)
      the exposed white sclera is void of any pigmentation, (2) humans possess the
      largest ratio of exposed sclera in the eye outline, and (3) the eye outline is
      extraordinarily elongated in the horizontal direction. The close correlation of
      the parameters reflecting (2) and (3) with habitat type or body size of the
      species examined suggested that these two features are adaptations for extending
      the visual field by eyeball movement, especially in the horizontal direction.
      Comparison of eye coloration and facial coloration around the eye suggested that
      the dark coloration of exposed sclera of nonhuman primates is an adaptation to
      camouflage the gaze direction against other individuals and/or predators, and
      that the white sclera of the human eye is an adaptation to enhance the gaze
      signal. The uniqueness of human eye morphology among primates illustrates the
      remarkable difference between human and other primates in the ability to
      communicate using gaze signals.

PMID- 11322804
TI  - Mortality rates among wild chimpanzees.
AB  - In order to compare evolved human and chimpanzees' life histories we present a
      synthetic life table for free-living chimpanzees, derived from data collected in
      five study populations (Gombe, Tai, Kibale, Mahale, Bossou). The combined data
      from all populations represent 3711 chimpanzee years at risk and 278 deaths.
      Males show higher mortality than females and data suggest some inter-site
      variation in mortality. Despite this variation, however, wild chimpanzees
      generally have a life expectancy at birth of less than 15 years and mean adult
      lifespan (after sexual maturity) is only about 15 years. This is considerably
      lower survival than that reported for chimpanzees in zoos or captive breeding
      colonies, or that measured among modern human hunter-gatherers. The low mortality
      rate of human foragers relative to chimpanzees in the early adult years may
      partially explain why humans have evolved to senesce later than chimpanzees, and
      have a longer juvenile period.

PMID- 11322805
TI  - What is a PhD?

PMID- 11322806
TI  - Meeting the challenge of problem-based learning: developing the facilitators.
AB  - Problem-based learning methodologies are now extensively utilized within
      contemporary nursing curricula. One factor which has been found to be vital to
      the successful use of these methodologies is the effectiveness of the
      facilitator. For some teachers, the facilitation of problem-based learning
      tutorials demands a shift from teacher- to student-centred instruction; for
      others it requires continuing development of present practice. It is proposed
      that this transformation or modification of teacher practice can be achieved
      through the use of group reflection for teacher development. This paper suggests
      that a group reflective practice strategy for facilitator development is more
      likely to prepare teachers to meet the demands of problem-based learning than
      traditional forms of staff development. The strategy proffered for teacher
      development has two phases: phase one establishes the group and centres
      discussion on the practice of problem-based learning facilitation; phase two
      involves critical analysis of personal practice of facilitation in the context of
      problem-based learning with a view to increased self-knowledge, ultimately
      leading to a change in practice. Changes to personal practice will be sustained
      by repeated participation in phase two. Essential to this ongoing participation
      will be recognition and support from the host organization.

PMID- 11322807
TI  - Student nurse attrition from pre-registration courses: investigating
      methodological issues.
AB  - There has been increasing recent interest in student nurse attrition. Despite a
      long history of research into the problem, attrition rates remain a cause for
      concern. This paper presents a review of the research undertaken in the UK,
      together with an international comparison. The foci of previous studies have been
      diverse and have included investigation of students' leaving reasons, their
      experience of stress, and course-related difficulties of students in progress.
      This review illustrates the complexity of issues surrounding student nurse
      discontinuation, highlighting a number of methodological limitations of prior
      research. These include the lack of a common definition of attrition, low
      response rates in surveys, and the imprecise definition of categories of leaving
      reasons. There is also a dearth of studies based on the perspectives of students.
      In the UK there is little documentation of whether measures have been adopted to
      reduce attrition and there is no evidence of evaluation. If future research is to
      be aimed at reducing attrition, these conceptual and methodological issues need
      to be addressed.

PMID- 11322808
TI  - Learning in the field: curriculum issues in a diploma in public health nursing.
AB  - Illuminative evaluation of a public health nursing curriculum shows that there
      was a gap between theory and practice, originating in the ways in which public
      health nursing was understood in the field, and therefore during students'
      placements, and in the university. The difference was chiefly in how the
      community staff and the lecturers understood primary health care. The former had
      a 'medical/professional' understanding of primary health care, implying that the
      professional knows best and that the client is an individual, a family or a
      group. The lecturers held a philosophy of primary health care with special
      emphasis on partnership with clients at all levels: individual, family, group and
      community; the partnership approach was intended to permeate the entire
      curriculum. Besides philosophical differences, there were other features of the
      theory practice gap demonstrated elsewhere. Fieldwork practice is integral to
      learning public health nursing so these contrasts created a serious disjunction
      within the curriculum. Actual and potential ways of improving curriculum
      integration are discussed.

PMID- 11322809
TI  - Northern Ireland--state of the arts? An evaluation of the use of the arts in
      teaching caring.
AB  - In recent years, nursing literature has shown a growing interest in the use of
      the arts as a teaching medium in nurse education. This interest has been further
      fostered by the advent of the curriculum revolution, which has underlined the
      need for nurse educationalists to attempt more innovative teaching strategies in
      helping their students develop caring skills. However, little has been done to
      establish the extent to which this medium is actually being used by teachers. The
      authors report on a survey which was carried out across Northern Ireland to
      gather evidence on the use of this strategy from teachers of nursing, midwifery
      and health visiting.

PMID- 11322810
TI  - An evaluation of a standards based portfolio.
AB  - In undergraduate and postgraduate nursing studies, the essay type assignment is
      commonly used to assess student learning. The literature suggests that of the
      alternatives for the assessment of learning, the use of portfolios may be an
      effective tool. A portfolio is generally conceptualized as a collection of the
      students best work or a collection of work that evidences incremental
      development. For a particular unit of learning, 'Nursing Business', second year
      undergraduate students in the Bachelor of Nursing programme were required to
      complete a portfolio. The assessment directed the students to meet specific
      criteria which in turn reflected the learning outcomes. Therefore the portfolio
      in this study is more appropriately described as a standards based portfolio
      (SBP). A SBP is a series of student work that seeks to address pre-determined
      learning outcomes. This study is an evaluation of student perceptions of a SPB
      and of interest to the study was the relationship between theory and practice,
      the availability of resources to complete the assignment and the contribution the
      portfolio made to the process of learning.

PMID- 11322811
TI  - Understanding mental health through reading selected literature sources: an
      evaluation.
AB  - The increasing use of the humanities in nurse education provides an alternative
      means of facilitating students' understanding of health issues. In part, this
      contributes to a critique of rationalist-technological approaches to education
      where knowledge is reduced to abstract, discernable and measured units. A more
      communal approach to education recognises the place of interpretation as part of
      learning and, within this, the significance of dialogue, identity, tradition,
      attachment and partnership. The reading of works of literature is one way in
      which the reader interprets texts in a multiplicity of ways in order to more
      fully understand the 'real' world. Mental health offers particular opportunities
      for literary descriptions. The evaluation of a learning unit within a mental
      health nursing branch programme where students read a number of works of
      literature is outlined. Results indicate a variety of student responses to use of
      such an approach. The authors assert the usefulness of these approaches in
      encouraging deeper understanding of complex issues faced in mental health nursing
      practice. At the same time, however, careful consideration is given to the place
      of such approaches within the overall philosophy of a curriculum programme.

PMID- 11322812
TI  - Barriers and gateways: a study of nursing students' utilisation of learning
      support resources.
AB  - Many first year nursing students require additional academic support from both
      their lecturers and learning resources. Anecdotal evidence at an Australian
      university suggested that 'at risk' students did not follow up lecturer referral.
      This study identified what learning resources were accessed and what factors
      influenced students' decisions to follow up or not to follow up lecturer
      referral. First-year nursing students (n =150) were surveyed towards the end of
      their second semester regarding their use of learning support services. Twelve
      students were randomly selected and interviewed regarding their use of learning
      support and their first year learning experience. Demographic data were analyzed
      using descriptive statistics. Qualitative data were subjected to content
      analysis. Results revealed learning support utilisation was related to age and
      publicity but unrelated to gender or culture. Older students entering through non
      traditional entry modes displayed a tendency to self refer to learning support.
      Younger students (<25 years) often lacked effective learning strategies and were
      reluctant to access on-campus learning support. For all students positive on and
      off campus support led to positive outcomes. Faculty and learning support
      lecturers need to foster integration of learning support for all students and
      encourage peer-learning partnerships within the foundation subjects.

PMID- 11322813
TI  - Postgraduate education for nurses: the Middlesex model.
AB  - Nurse education has been subject to many changes and much debate and criticism
      over recent years. What has become increasingly evident is that with the changing
      nature of nursing within society, nursing curricula have to be more flexible and
      dynamic if they are to meet a multiplicity of needs. There is also a need to
      recognize that many levels of curricula will be required to prepare the nurses of
      the future. At Middlesex University the development of specialist practice
      programmes at postgraduate diploma level, and preparation of nurses for a higher
      level of practice at masters level has required the development of a new
      curriculum model which allows both the individualization of academic programmes
      to meet the needs of nurses, their clients and the organization in which they
      work, and the integration of development and learning through practice. This
      model is built on the results of an evaluation of an existing postgraduate
      programme in interprofessional health care. Key features of the curriculum
      development include a structured collaboration between student, practice mentor
      and academic supervisor, and the use of a professional development portfolio to
      individualize the academic programme and facilitate autonomous learning.

PMID- 11322814
TI  - Attitudes toward older people among nursing students and registered nurses in
      Sweden.
AB  - Geriatric nursing is generally not considered to be a popular branch of nursing
      among Swedish nursing students and registered nurses. It is, therefore, important
      for nurse educators and others with responsibilities for the development of
      nursing to pay attention to trends of importance for the care of the elderly.
      Attitudes - conceptualized as feelings, knowledge, and readiness to act - may be
      one important factor. It has been reported that feelings toward older people may
      change with experience, age and gender. The aim of this study was to measure
      feelings toward older people among nursing students and registered nurses. A
      convenience sample of 151 undergraduate nursing students and 41 registered nurses
      in Sweden participated in the study. Data were collected through Kogan's Old
      People scale. The results confirmed earlier findings and showed that limited
      previous experience of care of older people, age <25 years, and male gender were
      significant factors for showing less favourable feelings towards the aged. In the
      education of nurses, goal-directed experience of elderly care is recommended in
      order to create positive feelings towards and interest in older people among
      students. It is also suggested that special considerations should be given to
      very young students and male students.

PMID- 11322815
TI  - Reassessing the concept of emotional labour in student nurse education: role of
      link lecturers and mentors in a time of change.
AB  - This article describes part of a follow-up study to Smith's (1992) original work
      on emotional labour, at a time when questions of the role, scope and crisis in
      nursing are a matter of local and national debate (Bradshaw 1999, Gillan 1999,
      Fabricius 1999, Feldman et al. 1999). The article addresses recent changes in
      nursing and nurse education (UKCC 1986, UKCC 1999a, DoH 1999, UKCC 1999b) as a
      means of exploring new patterns of learning to care in nursing. Less than a
      decade ago, emotional labour and helping students learn to care was part of the
      role of the sister/charge nurse (Ogier 1982, Fretwell 1982, Smith 1992). In this
      study, the role of the link lecturer, and mentor who currently shape the student
      nurse's learning experience, is the focus for evaluation.

PMID- 11322816
TI  - Reviewing the review process: towards good practice in the peer review of
      manuscripts submitted to nursing journals.
AB  - Publishing in peer reviewed journals is an essential activity for nurses working
      in higher education. This paper offers some reflections on the processes involve
      in the reviewing of articles submitted for publication, and explores some ways in
      which this system may be improved. All journals operate some kind of review
      process. This can range from, at one end, the editor making decisions about the
      suitability for publication of a submitted paper to, at the other end, papers
      being blind-reviewed by two (or sometimes more) external referees. This paper
      notes that there appears to be little or no consistency amongst the various
      nursing journals with respect to reviewing processes. Suggestions put forward in
      this article for consideration include: the standardisation of peer review
      systems across journals; the construction of guidelines for referees which
      caution against ad hominem attacks on authors; and the introduction of 'open'
      reviewing.

PMID- 11322821
TI  - Specific protein-DNA and protein-protein interaction in the hig gene system, a
      plasmid-borne proteic killer gene system of plasmid Rts1.
AB  - The hig (host inhibition of growth) gene system of plasmid Rts1 belongs to the
      plasmid-encoded proteic killer gene family. Among the proteic killer genes
      described so far, hig is unique in that the toxin gene (higB) exists upstream of
      the antidote gene (higA). There are two promoters in the hig locus, Phig and
      PhigA, and only the former, which expresses both higB and higA genes, is
      negatively controlled by HigA and HigB proteins. In this study, we purified HigA
      protein by means of GST fusion. The electrophoretic mobility shift assay using
      the purified protein revealed that HigA specifically bound to the Phig region,
      but not to PhigA. The HigA-binding sequence was determined by DNase I
      footprinting assay to be a 56-bp sequence that completely covered the -35 and -10
      boxes of Phig. The presence of two inverted repeats in the binding sequence and
      the identification of a dimer form of HigA by cross-linking experiment suggested
      that the protein bound to the Phig region as a dimer. HigB was purified as a GST
      fusion protein as well, though it was achieved only in the presence of HigA. HigA
      and GST-HigB formed a highly stable complex where the two proteins were present
      in an equimolar ratio.

PMID- 11322822
TI  - In vitro analysis of the terminator T(II) of the inhibitor antisense rna II gene
      from plasmid pMV158.
AB  - One element involved in the copy number control of plasmid pMV158 is the
      antisense RNA II. We have determined the precise size of this RNA synthesized in
      vitro. Transcript termination occurs at two consecutive template positions within
      a typical rho-independent terminator, T(II). Using a series of plasmid
      derivatives in which the T(II) terminator has been partially or totally removed,
      we have analyzed the relationship between the predicted stability of the RNA
      hairpin encoded by T(II) and the efficiency of in vitro intrinsic termination.
      All the plasmids of the pMV158 family, constituted so far of 19 replicons, harbor
      putative antisense RNA-encoding genes which share in common the relative location
      with respect to the essential rep gene, the small size, and the presence of rho
      independent transcription terminators.

PMID- 11322823
TI  - pUb6060: a broad-host-range, DNA polymerase-I-independent ColE2-like plasmid.
AB  - A ColE2-like, cryptic plasmid, pUB6060, of 5.8 kb has been found in a clinical
      isolate of Plesiomonas shigelloides. The complete sequence of pUB6060 has been
      determined and reveals a number of interesting features about the plasmid. The
      ColE2-like replication locus is linked to a functional ColE1-like mobilization
      locus. Replication is, unusually for ColE2 replicons, DNA polymerase-I
      independent and may involve two, rather than the usual one, plasmid-encoded
      functions. Additionally, it carries two ORFs encoding products of unknown
      function. The pUB6060 replicon maintains a moderate plasmid copy number (10 per
      chromosome copy) and permits replication in diverse gram-negative bacteria.

PMID- 11322825
TI  - A new insertion sequence, IS231M, in an autoagglutinable isolate of Bacillus
      thuringiensis.
AB  - An insertion sequence was isolated from an autoagglutinable strain of Bacillus
      thuringiensis. Analysis of its DNA sequence revealed high homology to the IS231
      family. The name IS231M is proposed for this new insertion sequence. IS231M is
      1652 bp long and is delimited by two imperfect 20-bp inverted repeat sequences
      with two mismatches, which are flanked by two perfect 11-bp direct repeats (DRs).
      The region upstream of the open reading frame, presumed to be able to form a
      stable hairpin structure, is particularly well conserved in IS231M. Based on
      primary nucleotide sequences, IS231M is most homologous to IS231F and IS231G and
      most distant from IS231V and IS231W. However, as opposed to the single
      transposase A ORF found in IS231A, -B, -C, -D, -F, and -G, IS231M has two
      overlapping open reading frames, ORF1 and ORF2, that could code for polypeptides
      of 334 and 143 amino acids, respectively. Whether IS231M is a functional
      transposable element remains to be determined.

PMID- 11322824
TI  - Construction and characterization of Streptococcus suis-Escherichia coli shuttle
      cloning vectors.
AB  - pSSU1, a native plasmid of Streptococcus suis DAT1, was used to construct pSET
      series shuttle vectors. In addition to the replication function of pSSU1, these
      vectors contain the multiple cloning sites and lacZ' gene from pUC19, which means
      that X-gal screening can be used to select recombinants in Escherichia coli.
      pSET1, pSET2, and pSET3 carry cat, spc, and both of these genes, respectively, as
      selectable markers. These vectors could be introduced into S. suis, E. coli,
      Salmonella typhimurium, S. pneumoniae, and S. equi ssp. equi by
      electrotransformation. The recA gene was cloned from S. suis and sequenced, and
      this information was used in the construction of a recA mutant of S. suis.
      Transformation frequencies and/or plasmid stability of all pSET vectors tested
      were decreased in both S. suis and E. coli recA mutants compared with the
      parental strains. These results suggested that functional RecA protein improved
      the maintenance of pSET vectors in both S. suis and E. coli. Moreover, cloning of
      the functional S. suis recA gene into pSET2 and complementation analysis of the
      recA mutant were successful in S. suis but not in E. coli. These results showed
      that pSET vectors are useful tools for cloning and analyzing S. suis genes in S.
      suis strains directly.

PMID- 11322826
TI  - Complete nucleotide sequence of the mycoplasma virus P1 genome.
AB  - Mycoplasma virus P1 is one of only four viruses isolated from the genus
      Mycoplasma. The host for P1, Mycoplasma pulmonis, possesses complex, phase
      variable restriction and modification enzymes and the Vsa family of phase
      variable surface proteins. The ability of P1 virus to infect host cells is
      influenced by these phase-variable systems, rendering P1 a valuable tool for
      assessing host properties. The double-stranded P1 DNA genome was sequenced
      (11,660 bp) and 11 ORFs were identified. The predicted P1 DNA polymerase is
      similar to that of phages that are known to have terminal protein (TP) attached
      to the 5' end of their genome, consistent with previous studies indicating that
      P1 DNA has covalently attached TP. Most of the other predicted P1 proteins have
      little sequence similarity to known proteins, and P1 virus is unrelated to the
      other mycoplasma virus, MAV1, for which the genome sequence is known. One of the
      predicted P1 proteins, the ORF 8 gene product, contains a repetitive collagen
      like motif characteristic of some bacteriophage tail fiber proteins and is a
      candidate for interacting with the Vsa proteins.

PMID- 11322827
TI  - Molecular characterization of a cryptic plasmid from Campylobacter jejuni.
AB  - Campylobacter jejuni is a leading bacterial cause of human enterocolitis.
      Molecular genetic characterization of this pathogen has been hampered by the lack
      of genetic tools that are functional in this organism. Cloning vectors commonly
      used in other organisms usually do not replicate within C. jejuni. To develop a
      system for functional analysis of C. jejuni genes, a small plasmid (pCJ01)
      identified in a poultry isolate of C. jejuni was sequenced and characterized in
      this study. By using inverse PCR, the full sequence of pCJ01 was amplified and
      subsequently determined. Results indicate that pCJ01 is a circular molecule of
      3212 bp, with a G + C content of 33.5%. A typical plasmid replication origin with
      iteron sequences is identified upstream of the DNA sequences encoding replication
      initiation proteins. Four open reading frames (ORFs) are present in pCJ01. ORF1
      and ORF2 share high homology with the putative RepA and RepB proteins,
      respectively, of known C. coli plasmids. ORF3 and ORF4, of unknown function, do
      not exhibit homology with any sequences deposited in the GenBank database.
      Hydropathy analysis predicts that ORF3 and ORF4 contain multiple stretches of
      hydrophobic amino acids, suggesting that they may encode transmembrane proteins.
      Since pCJ01 is a small plasmid and can be readily prepared from C. jejuni, it may
      be modified for use in molecular characterization of C. jejuni virulence genes.

PMID- 11322828
TI  - Tumors are unique organs defined by abnormal signaling and context.
AB  - Many cancer investigations have focussed on the eradication of the cancer cell
      itself and in doing so, overlook the inherent complexity and heterogeneity of
      solid tumors. Here, we argue that, in many cases, it is the altered communication
      within the tumor, rather than mutations per se, that is the defining
      characteristic of cancer. As a result, tumorigenesis can be indirectly initiated
      by environmental or inherited factors that affect the stromal cells. We propose
      that anticancer research might be more effective if aimed at eradicating the
      cause of abnormality rather than just treating the end result.

PMID- 11322829
TI  - Stromal cells can contribute oncogenic signals.
AB  - The majority of studies of neoplastic transformation have focused attention on
      events that occur within transformed cells. These cell autonomous events result
      in the disruption of molecular pathways that regulate basic activities of the
      cells such as proliferation, death, movement and genomic integrity. Other studies
      have addressed the microenvironment of tumor cells and documented its importance
      in supporting tumor progression. Recent work has begun to expand on these initial
      studies of tumor microenvironment and now provide novel insights into the
      possible initiation and progression of malignant cells. This review will address
      the transforming effect of stromal cells on epithelial components.

PMID- 11322830
TI  - Tumor invasion as dysregulated cell motility.
AB  - Investigations across a range of disciplines over the past decade have brought
      the study of cell motility and its role in invasion to an exciting threshold. The
      biophysical forces proximally involved in generating cell locomotion, as well as
      the underlying signaling and genomic regulatory processes, are gradually becoming
      elucidated. We now appreciate the intricacies of the many cellular and
      extracellular events that modulate cell migration. This has enabled the
      demonstration of a causal role of cell motility in tumor progression, with
      various points of 'dysregulation' of motility being responsible for promoting
      invasion. In this paper, we describe key fundamental principles governing cell
      motility and branch out to describe the essence of the data that describe these
      principles. It has become evident that many proposed models may indeed be
      converging into a tightly-woven tapestry of coordinated events which employ
      various growth factors and their receptors, adhesion receptors (integrins),
      downstream molecules, cytoskeletal components, and altered genomic regulation to
      accomplish cell motility. Tumor invasion occurs in response to dysregulation of
      many of these modulatory points; specific examples include increased signaling
      from the EGF receptor and through PLC gamma, altered localization and expression
      of integrins, changes in actin modifying proteins and increased transcription
      from specific promoter sites. This diversity of alterations all leading to tumor
      invasion point to the difficulty of correcting causal events leading to tumor
      invasion and rather suggest that the underlying common processes required for
      motility be targeted for therapeutic intervention.

PMID- 11322831
TI  - Lamellipodia in invasion.
AB  - In vivo imaging of GFP-labeled metastatic tumor cells reveals cell orientation
      towards blood vessels. Orientation of tumor cells during chemotactic responses to
      ligands such as EGF begins with lamellipod extension. Evaluation of some of the
      downstream events in lamellipod extension indicates: (1) plasma membrane
      distribution of the EGF receptor is uniform but internalized receptor accumulates
      on the side of the cell closest to the source of EGF; (2) the alpha p110 isoform
      of PI-3 kinase is required; and (3) protrusion of the lamellipod relies upon the
      combined actions of the Arp2/3 complex and cofilin for generation of filamentous
      actin.

PMID- 11322832
TI  - Towards a mechanistic understanding of tumor invasion--lessons from the
      alpha6beta 4 integrin.
AB  - This review explores the mechanistic basis of carcinoma migration and invasion by
      focusing on the contribution of integrins. Integrins are essential for invasion
      not only for their ability to mediate physical interactions with extracellular
      matrices, but also for their ability to regulate signaling pathways that control
      actin dynamics and cell movement, as well as for growth and survival. Our
      comments center on a unique member of the integrin family, the alpha 6 beta 4
      integrin, which is a receptor for the laminin family of basement membrane
      components. Numerous studies have implicated this integrin in the invasion of
      solid tumors and have provided a rationale for studying the mechanistic basis of
      its contribution to the invasive process. Such studies have revealed novel
      insights into the mechanism of carcinoma invasion that involve both the dynamics
      of cell migration and signaling pathways that regulate this migration.

PMID- 11322833
TI  - Proteases in invasion: matrix metalloproteinases.
AB  - The role of proteases in general, and the matrix metalloproteinases in
      particular, in tumor invasion and metastasis is well established. However, the
      classic view that these enzymes simply provide a mechanism for the breakdown of
      connective tissue barriers has been challenged. This overview summarizes recent
      evidence to support the changing view of the role of matrix metalloproteinases in
      cancer progression. First we briefly review the central role of cell invasion in
      cancer progression and also the matrix metalloproteinase family members. We then
      focus on the emerging roles for these enzymes in cancer progression, including
      the role of matrix metalloproteinases in cell proliferation and release of growth
      factors, cell migration and in modification of the extracellular matrix to reveal
      cryptic sites that alter cell behaviour.

PMID- 11322834
TI  - Scatter factors and invasive growth.
AB  - Scatter factors are unequivocal signals governing a genetic program that includes
      cell detachment, repulsion, protection from apoptosis, invasiveness of
      extracellular matrices and proliferation. This pleiomorphic response is defined
      as 'invasive growth'. Under physiological conditions, it leads to morphogenic
      cell movements through the matrix, and--primarily--to ordered building of
      epithelial tubules. Dysfunctions in invasive growth cause enhanced proliferation,
      uncontrolled migration into surrounding tissues, and failure to differentiate,
      events that foster tumour growth and invasiveness. Scatter factors act through
      tyrosine kinase receptors that belong to the Met oncogene family. Here we discuss
      how alterations of these receptors or of their signal transduction pathways are
      responsible for cancer onset and progression towards metastasis.

PMID- 11322835
TI  - Regulation of the cytoskeleton by Rho-family GTPases: implications for tumour
      cell invasion.
AB  - Rho-like GTPases regulate both cell-cell and cell-matrix adhesions and can
      influence the motile and invasive properties of tumour cells in vitro. Increased
      Rac signalling can promote either cell-cell adhesion or motility depending on the
      cell type and composition of the extracellular matrix. Ultimately, the balance of
      Rac and Rho activities and intracellular localization appears to be critical in
      determining the cellular phenotype.

PMID- 11322836
TI  - Drug-related adverse events: a readers' guide to assessing literature reviews and
      meta-analyses.

PMID- 11322837
TI  - The future of academic medical centers in the United States: passing through the
      valley of the shadow of death.
AB  - The last 2 decades witnessed remarkable events in the life of academic medical
      centers (AMCs) in the United States. Twenty years ago, AMCs were thriving as the
      era of fee-for-service medicine came to a close: clinical departments were
      expanding, hiring new faculty members, purchasing new equipment as necessary, and
      funding research projects and protected research time with the abundant clinical
      revenues. The subsequent 20 years since that golden era came to a close witnessed
      teh disappearance of these expansionary trends. Departments have contracted,
      protected research time and start-up funds have declined precipitously, and many
      faculty members are infected with a sense of malaise and fear for the future.

PMID- 11322838
TI  - An update on hypercoagulable disorders.
AB  - Venous thrombosis is a cause of considerable morbidity and is often responsible
      for chronic venous disorders that frequently lead to visits to dermatologists and
      others involved in wound healing. Over the past several years, many new causes of
      thrombophilia have been identified and have dramatically altered the approach to
      patients presenting with thrombosis. Newly described abnormalities associated
      with thrombophilia include the syndrome of activated protein C resistance, the
      prothrombin 20210A mutation, hyperhomocysteinemia, and elevated levels of
      coagulation factors VIII and XI. Clinicians can now frequently determine causes
      of thromboses that have previously been deemed idiopathic.

PMID- 11322839
TI  - Natural rubber latex allergy: a problem of interdisciplinary concern in medicine.
AB  - In the past 10 years, IgE-mediated allergy to natural rubber latex has become a
      significant health problem in industrialized countries, especially among health
      care workers, patients with congenital malformations, and children with a history
      of multiple surgical interventions. Curative treatment inducing immunological
      tolerance in formerly sensitized patients is experimental and not yet generally
      available. Therefore, it is important to be aware of the seriousness of latex
      allergy and to understand the risk factors leading to this allergy. Preventive
      measures are needed to decrease the incidence of natural rubber latex
      sensitization. This article gives a brief review of the current state of
      knowledge concerning latex allergy, including a definition of latex,
      epidemiological data, identified allergens, the clinical spectrum, diagnostic
      procedures, cross-reactions, preventive measures, the legislative background, and
      economics.

PMID- 11322840
TI  - Low-dose oral contraceptive use and the risk of myocardial infarction.
AB  - BACKGROUND: Studies of oral contraceptives (OCs) containing 50 microg or more of
      estrogen suggest an increased risk of myocardial infarction (MI) among current
      users, particularly if they smoke heavily. OBJECTIVE: To assess whether use of
      the newer lower-dose OCs increases the risk of MI. METHODS: A case-control study
      was conducted from January 1985 through March 1999 in 75 hospitals in the greater
      Boston and greater-Philadelphia areas. Data on OC use and MI risk factors were
      obtained by interview from 627 women with a nonfatal first MI (cases) and 2947
      female hospital controls younger than 45 years. RESULTS: The overall odds ratio
      (OR) for current OC use relative to never used was 1.3 (95% confidence interval
      [CI], 0.8-2. 2). The OR was elevated, 2.5 (95% CI, 0.9-7.5), among heavy smokers
      (>/=25 cigarettes per day) but close to 1.0 among lighter smokers (OR = 0.8) and
      nonsmokers (OR = 1.3). For current OC use together with heavy smoking relative to
      nonuse and nonsmoking, the OR was 32 (95 % CI, 12-81), considerably greater than
      that for heavy smoking alone, 12 (95% CI, 8.6-16). The ORs did not vary according
      to the type of formulation or the dose of estrogen; there were too few users to
      assess the new 20-microg preparations. Past OC use was unrelated to risk.
      CONCLUSION: Current use of low-dose OCs in the United States is unrelated to an
      increased risk of MI among nonsmokers and light smokers, but users who smoke
      heavily may be at greatly increased risk.

PMID- 11322841
TI  - Individualized stress management for primary hypertension: a randomized trial.
AB  - OBJECTIVE: To test the efficacy of individualized stress management for primary
      hypertension in a randomized clinical trial with the use of ambulatory blood
      pressure (BP) measures. METHODS: Men and women aged 28 to 75 years with mean
      ambulatory BP greater than 140/90 mm Hg received 10 hours of individualized
      stress management by means of semistandardized treatment components. They were
      randomly assigned to immediate treatment (n = 27) or a wait list control group (n
      = 33). Participants on the wait list were subsequently offered treatment. Six
      month follow-up data were available from 36 of the 45 participants who completed
      treatment. Measures were 24-hour ambulatory BP, lipid levels, weight, and
      psychological measures. RESULTS: Blood pressure was significantly reduced in the
      immediate treatment group and did not change in control subjects (-6.1 vs +0.9 mm
      Hg for systolic and -4.3 vs +0.0 mm Hg for diastolic pressure). When the wait
      list control group was later treated, BP was similarly reduced by -7.8 and -5.2
      mm Hg, and for the combined sample, total change at follow-up was -10.8 and -8.5
      mm Hg. Level of BP at the beginning of treatment was correlated with BP change (r
      = 0.45 [P<.001] and 0.51 [P<.001], respectively), and amount of systolic BP
      change was positively correlated with reduction in psychological stress (r =
      0.34) and change in anger coping styles (r = 0.35-0.41). CONCLUSIONS:
      Individualized stress management is associated with ambulatory BP reduction. The
      effects were replicated and further improved by follow-up. Reductions in
      psychological stress and improved anger coping appear to mediate the reductions
      in BP change.

PMID- 11322842
TI  - Randomized trial comparing traditional Chinese medical acupuncture, therapeutic
      massage, and self-care education for chronic low back pain.
AB  - BACKGROUND: Because the value of popular forms of alternative care for chronic
      back pain remains uncertain, we compared the effectiveness of acupuncture,
      therapeutic massage, and self-care education for persistent back pain. METHODS:
      We randomized 262 patients aged 20 to 70 years who had persistent back pain to
      receive Traditional Chinese Medical acupuncture (n = 94), therapeutic massage (n
      = 78), or self-care educational materials (n = 90). Up to 10 massage or
      acupuncture visits were permitted over 10 weeks. Symptoms (0-10 scale) and
      dysfunction (0-23 scale) were assessed by telephone interviewers masked to
      treatment group. Follow-up was available for 95% of patients after 4, 10, and 52
      weeks, and none withdrew for adverse effects. RESULTS: Treatment groups were
      compared after adjustment for prerandomization covariates using an intent-to
      treat analysis. At 10 weeks, massage was superior to self-care on the symptom
      scale (3.41 vs 4.71, respectively; P =.01) and the disability scale (5.88 vs
      8.92, respectively; P<.001). Massage was also superior to acupuncture on the
      disability scale (5.89 vs 8.25, respectively; P =.01). After 1 year, massage was
      not better than self-care but was better than acupuncture (symptom scale: 3.08 vs
      4.74, respectively; P =.002; dysfunction scale: 6.29 vs 8.21, respectively; P
      =.05). The massage group used the least medications (P<.05) and had the lowest
      costs of subsequent care. CONCLUSIONS: Therapeutic massage was effective for
      persistent low back pain, apparently providing long-lasting benefits. Traditional
      Chinese Medical acupuncture was relatively ineffective. Massage might be an
      effective alternative to conventional medical care for persistent back pain.

PMID- 11322843
TI  - Management of severe hypokalemia in hospitalized patients: a study of quality of
      care based on computerized databases.
AB  - BACKGROUND: While administrative databases are used to assess general indicators
      of quality of care, a detailed audit of the process of clinical care usually
      requires review of hospital medical records. OBJECTIVE: To evaluate the
      feasibility of assessing the management of severe hypokalemia using computerized
      administrative and laboratory databases. METHODS: The study included all patients
      hospitalized in 1997 who experienced serum potassium levels of less than 3.0
      mmol/L at Hadassah University Hospital, Jerusalem, Israel, a tertiary care
      center. Using the computerized databases, we measured the following: (1) whether
      a subsequent serum potassium test was performed, (2) time to the subsequent test
      and to normalization of the serum potassium level, (3) achievement of
      normokalemia, and (4) in-hospital mortality. In a random subsample of 100
      patients, these measures were compared with the blinded assessment of the quality
      of medical management of hypokalemia, as determined from medical records, using
      predetermined criteria for adequate management. RESULTS: The computerized
      databases revealed that severe hypokalemia occurred in 866 patients (2.6% of the
      yearly hospitalizations): 55 patients (6.4%) had no subsequent serum potassium
      levels measured, and 260 (30.0%) were discharged from the hospital with a
      subnormal potassium level. The mean time to a subsequent test was 20 hours, and
      to normokalemia, 50 hours; both intervals varied by department. In-hospital
      mortality was 20.4%, or 10-fold that of the entire hospitalized population. A
      review of hospital medical records revealed inadequate clinical management of
      hypokalemia in 24%, which was associated with nonperformance of a subsequent test
      (likelihood ratio, 8.4), failure to normalize the serum potassium level
      (likelihood ratio, 4.2), discharge from the hospital with a subnormal potassium
      level (likelihood ratio, 2.1), and in-hospital death (likelihood ratio, 2.5), all
      of which could be determined by the computerized databases. CONCLUSIONS: The
      computerized laboratory database is useful in ascertaining the prevalence of
      severe hypokalemia and in assessing shortcomings in its management. Databases can
      be used to derive valid and efficient measures of the quality of the clinical
      management of electrolyte disorders.

PMID- 11322844
TI  - Use of medications with anticholinergic effect predicts clinical severity of
      delirium symptoms in older medical inpatients.
AB  - BACKGROUND: Use of anticholinergic (ACH) medications is a biologically plausible
      and potentially modifiable risk factor of delirium, but research findings are
      conflicting regarding its association with delirium. OBJECTIVES: To evaluate the
      longitudinal association between use of ACH medications and severity of delirium
      symptoms and to determine whether this association is modified by the presence of
      dementia. PATIENTS AND METHODS: A total of 278 medical inpatients 65 years and
      older with diagnosed incident or prevalent delirium were followed up with
      repeated assessments using the Delirium Index for up to 3 weeks. Exposure to ACH
      and other medications was measured daily. The association between change in
      medication exposure in the 24 hours preceding a Delirium Index assessment was
      assessed using a mixed linear regression model. RESULTS: During follow-up (mean
      +/- SD, 12.3 +/- 7.0 days), 47 medications with potential ACH effect were used in
      the population (mean, 1.4 medications per patient per day). Increase in delirium
      severity was significantly associated with several measures of ACH medication
      exposure on the previous day, adjusting for dementia, baseline delirium severity,
      length of follow-up, and number of non-ACH medications taken. Dementia did not
      modify the association between ACH medication use and delirium severity.
      CONCLUSION: Exposure to ACH medications is independently and specifically
      associated with a subsequent increase in delirium symptom severity in elderly
      medical inpatients with diagnosed delirium.

PMID- 11322845
TI  - Predictors of persistence of use of the novel antidiabetic agent acarbose.
AB  - BACKGROUND: A carbose is the first of a new class of antidiabetic agents, the
      alpha-glucosidase inhibitors. This study characterizes and identifies predictors
      of persistence of use of acarbose. METHODS: Medical, pharmaceutical, and
      demographic records were extracted for 2 cohorts of patients (social assistance
      recipients and seniors) from the databases of Quebec's provincial health plan.
      Patients were eligible for inclusion if they had received their first
      dispensation of acarbose between August 1, 1996, and December 31, 1997. The
      observation period included at least 1 year before the first dispensation and a
      minimum of 4 months after. RESULTS: New users of acarbose included 216 social
      assistance recipients and 677 seniors who were followed up for 82 914 and 270 041
      person-days, respectively. Median persistence with acarbose treatment was 83 days
      (95% confidence interval, 75-105 days) for social assistance recipients and 105
      days (95% confidence interval, 90-119 days) for seniors. In both cohorts,
      treatment by an endocrinologist vs another physician predicted longer treatment
      persistence. In the seniors cohort, additional determinants of (earlier)
      treatment discontinuation included a higher initial daily dose, previous
      treatment with insulin, and consultation with a gastroenterologist after
      treatment initiation. CONCLUSIONS: New users of acarbose showed low persistence
      in 2 cohorts of beneficiaries of Quebec's provincial health plan. Prescribing
      specialist was an important predictor of persistence in seniors and the socially
      assisted. The importance of 4 additional factors in seniors only led to
      hypotheses concerning population differences in treatment expectations and in the
      occurrence and tolerance of adverse effects.

PMID- 11322846
TI  - Tetraparesis by isolated cervical spine metastasis as manifestation of occult
      cancer.

PMID- 11322847
TI  - Thigh hematoma after femoral venipuncture in a patient treated with low-molecular
      weight heparin.

PMID- 11322848
TI  - Diabetes insipidus due to Streptococcus pneumoniae meningitis.

PMID- 11322849
TI  - Are fewer patient isolations justified for active tuberculosis?

PMID- 11322851
TI  - Determining the serum concentration alone is not sufficient to justify potassium
      administration.

PMID- 11322853
TI  - Interventions in end-of-life care.

PMID- 11322855
TI  - Quinidine and malaria.

PMID- 11322857
TI  - Old antithrombotics: ready to retire?

PMID- 11322858
TI  - Postmenopausal oestrogen replacement therapy and atherosclerosis: can current
      compounds provide cardiovascular protection?
AB  - The natural oestrogen, 17 beta-oestradiol, has been implicated in protection from
      atherosclerosis, a chronic systemic vascular disease with an inflammatory
      component accounting for the majority of morbidity and mortality in Western
      countries. Despite the protective effects of 17 beta-oestradiol in premenopausal
      women and experimental evidence demonstrating inhibitory effects of oestrogen on
      atherosclerosis progression, it is currently unclear whether hormone replacement
      therapy can affect cardiovascular morbidity and mortality in postmenopausal
      women. The recent advances in understanding the mechanisms of oestrogen action
      demonstrated roles for different oestrogen receptors and oestrogen metabolites in
      the pathogenesis of vascular injury and endothelial cell dysfunction. However,
      their respective role in the process of atherogenesis remains yet to be
      elucidated. Moreover, the availability of novel drugs with tissue- and/or
      receptor-specific actions will help to understand the role of oestrogen in
      cardiovascular diseases. Several ongoing large-scale clinical trials using
      opposed or unopposed replacement therapy with natural or synthetic oestrogens, or
      selective oestrogen receptor modulators (SERMs) will resolve the question whether
      the drugs currently available have therapeutic potential to interfere with the
      progression of atherosclerosis and its complications.

PMID- 11322859
TI  - Novel therapeutics for the treatment of paediatric pulmonary arterial
      hypertension.
AB  - The treatment of paediatric pulmonary arterial hypertension is challenging due to
      the serious nature of the disease, its rapid progression and the limited
      treatment options available. However, recent advances in the treatment of
      pulmonary arterial hypertension may offer significant improvements for patients
      suffering from this condition. Novel treatment options include prostacyclin
      analogues and endothelin receptor antagonists. A comprehensive review of the
      newer agents, with an emphasis on the pathobiology/pathophysiology of pulmonary
      arterial hypertension provides insight into future management of paediatric
      pulmonary arterial hypertension.

PMID- 11322860
TI  - Development and therapeutic indications of orally-active non-peptide vasopressin
      receptor antagonists.
AB  - Vasopressin (AVP) is a cyclic nonapeptide hormone that exhibits many
      physiological effects including free water reabsorption, vasoconstriction,
      cellular proliferation and adrenocorticotrophic hormone (ACTH) secretion. In a
      healthy organism, AVP plays an important role in the homeostasis of fluid
      osmolality and volume status. However, in several diseases or conditions such as
      the syndrome of inappropriate secretion of AVP (SIADH), congestive heart failure,
      arterial hypertension, liver cirrhosis, nephrotic syndrome, dysmenorrhoea and
      ocular hypertension, AVP may play an important role in their pathophysiology.
      Recently, orally-active non-peptide AVP receptor antagonists were developed by
      random screening of chemical entities and optimisation of lead compounds. These
      include agents specific for the V(1)-vascular and V(2)-renal AVP receptor
      subtypes. Dual V(1)/V(2) AVP receptor antagonists are also being studied. Some of
      these non-peptide receptor antagonists have been studied extensively, while
      others are currently under investigation. Potential therapeutic indications for
      AVP receptor antagonists comprise: 1) The blockade of V(1)-vascular AVP receptors
      in arterial hypertension, congestive heart failure, Raynaud's syndrome,
      peripheral vascular disease and dysmenorrhea. 2) The blockade of V(2)-renal AVP
      receptors in the syndrome of inappropriate secretion of vasopressin, congestive
      hart failure, liver cirrhosis, nephrotic syndrome and any state of excessive
      retention of free water and subsequent dilutional hyponatraemia. 3) The blockade
      of V(3)-pituitary AVP receptors in ACTH-secreting tumours. This review examines
      the pharmacology of orally-active non-peptide AVP receptor antagonists and their
      clinical applications.

PMID- 11322861
TI  - Therapeutic potential of Na-H exchange inhibitors for the treatment of heart
      failure.
AB  - The Na-H exchanger (NHE) represents a family of transporters which regulate
      intracellular pH by removing protons in exchange for sodium influx in an
      electroneutral 1:1 stoichiometric relationship. Six isoforms have thus far been
      identified with the NHE-1 subtype representing the primary isoform in the cardiac
      cell. It is well-established that NHE-1 contributes to cardiac injury produced by
      ischaemia and reperfusion and inhibitors of the antiporter exert excellent
      cardioprotection. More recent evidence suggests that NHE-1 may also be important
      for cell growth and may contribute to the maladaptive remodelling which
      contributes to heart failure particularly the early hypertrophic responses.
      Evidence from in vitro studies suggest that NHE-1 inhibitors attenuate
      cardiomyocyte hypertrophy in response to various stimuli whereas in vivo studies
      report substantial attenuation of both hypertrophy and heart failure by these
      agents, especially after myocardial infarction. Accordingly, NHE-1 inhibitors
      could emerge as important therapeutic tools for the attenuation and treatment of
      heart failure.

PMID- 11322862
TI  - Advances in the development of thrombin inhibitors.
AB  - Thromboembolic diseases are a major cause of morbidity and mortality,
      particularly in the Western world, which has stimulated enormous research efforts
      by the pharmaceutical industry to introduce new antithrombotic therapies. One
      strategy is the development of direct inhibitors of the serine protease thrombin,
      which holds a central position in the final steps of the blood coagulation
      cascade and in platelet activation. At present there is only limited clinical use
      of some parenteral preparations of thrombin inhibitors in acute situations,
      especially when the common antithrombotic drugs heparin, warfarin and aspirin are
      ineffective or associated with side effects. However, for use in prophylaxis of
      thrombotic diseases such inhibitors should be orally available, must be safe to
      avoid bleeding complications and should have an appropriate half-life, allowing
      once or twice daily dosing to maintain adequate antithrombotically effective
      blood levels. Details of several new and potent thrombin inhibitors have been
      published during the last years. For some of them oral bioavailability is claimed
      and they are effective in in vitro coagulation assays. However, most of them
      showed only limited efficacy in animal studies with respect to the doses
      administered. For that reason, effort is concentrated on the evaluation and
      optimisation of the overall physicochemical characteristics of the inhibitors in
      order to improve the pharmacokinetics and, thus, the development of promising
      drug candidates. Nevertheless, only careful clinical studies can give clear
      answers about the true therapeutical benefit of new developments in this field.
      This review summarises the current status of direct thrombin inhibitors which are
      already in clinical use and clinical development and gives an overview on
      recently published and promising new compounds.

PMID- 11322863
TI  - Inhibitors of platelet signal transduction as anti-aggregatory drugs.
AB  - In the treatment and prevention of cardiovascular diseases, inhibition of
      platelet aggregation is of fundamental importance. Inhibition of platelet
      aggregation can be achieved by either inhibition of membrane receptors or by
      interception of signalling pathways. While receptor antagonism provides high
      specificity, the inhibition of platelet signal transduction is more effective.
      The effectiveness results from the inhibition of platelets, regardless of the
      cause of activation. These common pathway inhibitors are either intercepting
      platelet activating mechanisms or amplifying the action of endogenous platelet
      inhibitors. The physiological anti-aggregants are the endothelial factors NO and
      prostacyclin, which elevate intracellular cGMP or cAMP content, respectively. By
      administration of NO-releasing agents, prostacyclin analogues or other cyclic
      nucleotide elevating drugs the platelet anti-aggregatory action of endothelial
      factors can be effectively mimicked. Besides antiplatelet activity these drugs
      also act on vascular smooth muscle causing relaxation and therefore vasodilation,
      an additional beneficial effect. Inhibition of phosphodiesterases causes
      elevation of platelet cyclic nucleotide content and thus inhibits platelet
      aggregation and causes vasodilation. Another relevant target for anti-aggregatory
      treatment is the arachidonic acid metabolic pathway. This pathway can be
      intercepted by blockade of either cyclooxygenase-1 (COX-1) or thromboxane
      synthase. Inhibition of these enzymes may be further amplified by additional
      antagonism of the thromboxane receptor thus not only preventing formation of
      thromboxane but also activation of thromboxane receptor by thromboxane
      precursors, which were particularly effective in clinical trials. In vivo these
      precursors may be metabolised to prostacyclin in the endothelium and consequently
      provide additional platelet anti-aggregatory activity. A rather new target for
      platelet anti-aggregatory treatment is the ecto-nucleotidase CD-39 which limits
      the plasma level of nucleotides. While several of the novel anti-aggregatory
      drugs were disappointing in clinical studies combinations of drugs with different
      effector enzymes showed potent antithrombotic efficacy.

PMID- 11322864
TI  - Intravascular radiation for the prevention of recurrence of restenosis in
      coronary arteries.
AB  - Despite the use of new technology and adjunctive pharmacological therapy, in
      stent restenosis continues to hamper the outcome of approximately 150,000
      patients who undergo stented coronary angioplasty in the US annually. While
      coronary stenting eliminates elastic recoil and vessel contracture by acting as a
      mechanical scaffold within the vessel, it is unable to inhibit excessive
      neointimal formation and may actually promote it. For years, the growth
      inhibiting properties of ionising radiation have been used successfully to
      control benign proliferative disorders. Based on this experience, vascular
      brachytherapy, the intravascular delivery of radiation, was viewed as a viable
      solution to inhibit neointimal hyperplasia. A series of studies performed in
      animal models identified the mechanisms by which radiation may reduce restenosis.
      Data from these studies showed that endovascular radiation reduces restenosis by
      inhibiting cell proliferation and by inducing favourable remodelling. The success
      of these initial studies led to several double-blind, multicentre, placebo
      controlled, randomised, clinical trials evaluating intravascular radiation, with
      either gamma- or beta-radiation sources, proved to be an effective solution for
      the prevention of neointimal proliferation and restenosis. However, an increased
      rate of late thrombosis in patients who had received intracoronary radiation did
      evolve from the initial use of this therapy. Prolonged antiplatelet therapy and a
      reduction in the number of new stents placed at the time of radiation has been
      shown to minimise these complications. Other concerns that still need to be
      resolved include edge effect and geographical miss. Intravascular brachytherapy
      is currently the only approved therapy for this complex disease. It is clear that
      there are still on-going concerns that will eventually be clarified when the long
      term results from ongoing clinical trials around the world become available.

PMID- 11322865
TI  - Novel approaches to the treatment of chronic graft-versus-host disease.
AB  - Chronic graft-versus-host disease (cGvHD) continues to be the major problem in
      long-term survivors of allogeneic haematopoietic stem cell transplants and is the
      principal cause of morbidity and non-relapse mortality. Over the past twenty
      years, diagnosis, prophylaxis and treatment of cGvHD have slowly evolved. An
      effective therapy for cGvHD is designed to prevent complications through
      targeting the disease mechanisms. None of the present therapies for cGvHD are
      successful in the majority of patients. Conventional drugs in different
      combinations can control the disease in approximately 50% of patients. Attempts
      to improve survival have led to evaluation of several alternative approaches in
      the treatment of refractory cGvHD with varying degrees of success. Clinical
      trials are needed to establish the role of these new approaches in the treatment
      of cGvHD as first line or salvage therapy without causing significant side
      effects. This review summarises the currently available knowledge on conventional
      and new treatment approaches for cGvHD.

PMID- 11322866
TI  - Advances in experimental treatment of beta-thalassaemia.
AB  - Beta-thalassaemia is highly prevalent and world wide in its distribution. The
      gene to modify the clinical course of patients with transfusion-dependent
      thalassaemia (thalassaemia major), the gamma-globin gene, is already present in
      these patients but silenced in the course of development. During erythropoiesis,
      progenitors are believed to go through a phase where the milieu favours gamma
      globin production. One pharmacological strategy to increase gamma-globin
      production is directed at recruiting such early progenitors through the use of
      cytotoxic agents (+/- erythropoietin) that presumably deplete more mature
      progenitors. Another promising strategy is to use chromatin-modifying agents that
      prevent the silencing of the gamma-globin gene that occurs during development.
      These agents, the methyl-transferase inhibitors and histone deacetylase
      inhibitors, either alone or in combination, may be able to produce the robust
      increase in gamma-globin and hence fetal haemoglobin and total haemoglobin,
      needed to successfully treat thalassaemia major. Studies of these agents, which
      are already available for clinical trials, should be encouraged.

PMID- 11322867
TI  - An update on nesiritide for treatment of decompensated heart failure.
AB  - In the July 1999 issue of this publication, we described the chemical properties,
      pharmacology and clinical trials involving nesiritide as a therapeutic agent for
      patients with decompensated heart failure (Exp. Opin. Invest. Drugs) (1999)
      8(7):1063--1072). At the time of publication, the US Food and Drug Administration
      reviewed the clinical experience with the compound and did not approve the drug
      for clinical use. More data were requested regarding safety issues, comparison
      with nitroglycerine, onset of effects, need for invasive haemodynamic monitoring
      and symptomatic improvement. The VMAC Study was designed to address these issues.
      A dosing regimen, 0.2 microgram/kg bolus followed by 0.01 microg/kg/min
      continuous infusion, was chosen to provide rapid onset of actions and
      haemodynamic improvement without a high incidence of symptomatic hypotension.
      Nesiritide was superior to iv. nitroglycerine in its haemodynamic effects, easier
      to administer without the need for dose titration and better tolerated overall.
      The drug could be administered safely without the need for invasive haemodynamic
      monitoring. Symptomatic hypotension occurred in 4% of patients. Beneficial
      haemodynamic effects correlated with symptomatic improvement in heart failure
      patients. Nesiritide appears to be an ideal first-line agent for treatment of
      patients with acutely decompensated heart failure.

PMID- 11322868
TI  - The spironolactone renaissance.
AB  - Until recently, spironolactone was considered only as an antagonist at the
      aldosterone receptors of the epithelial cells of the kidney and was used
      clinically in the treatment of hyperaldosteronism and, occasionally, as a K(+)
      sparing diuretic. The spironolactone renaissance started with the experimental
      finding that spironolactone reversed aldosterone-induced cardiac fibrosis by a
      cardiac action. Experimentally, spironolactone also has direct effects on blood
      vessels. Spironolactone reduces vascular fibrosis and injury, inhibits
      angiogenesis, reduces vascular tone and reduces portal hypertension. The
      rationale for the Randomized Aldactone Evaluation Study (RALES) of spironolactone
      in heart failure was that 'aldosterone escape' occurred through non-angiotensin
      II mechanisms. The RALES clinical trial was stopped early when it was shown that
      there was a 30% reduction in risk of death among the spironolactone patients. In
      RALES, spironolactone also reduced hospitalisation for worsening heart failure
      and improved the symptoms of heart failure. Other recent clinical trials have
      shown that spironolactone reduces cardiac and vascular collagen turnover,
      improves heart variability, reduces ventricular arrhythmias, improves endothelial
      dysfunction and dilates blood vessels in human heart failure and these effects
      probably all contribute to the increased survival in heart failure.
      Spironolactone may also be useful in the treatment of left ventricular
      hypertrophy, portal hypertension and cirrhosis. There have also been some recent
      small clinical trials of spironolactone as an anti-androgen showing potential in
      acne, hirsutism and precocious puberty.

PMID- 11322869
TI  - Levosimendan: a parenteral calcium-sensitising drug with additional vasodilatory
      properties.
AB  - Levosimendan (Simdax) is a new inodilator developed specifically for the
      treatment of decompensated heart failure. Its inotropic mechanism is based on
      calcium sensitisation of myofilaments and its vasodilator actions are related to
      the opening of ATP-dependent K-channels in the vasculature. Since the inotropic
      action of levosimendan does not require an increase in cytosolic free calcium, it
      is less arrhythmogenic than the conventional parenteral beta-agonist inotropes or
      PDE III inhibiting drugs. Due to the calcium-dependent binding of the drug to
      troponin C, levosimendan, unlike some other calcium-sensitising drugs, does not
      prolong diastolic relaxation of the myocytes but acts in synergy with the
      intramyocellular calcium levels. Furthermore, due to the anti-ischaemic effects
      of the K-channel opening in myocytes, levosimendan can be used during myocardial
      ischaemia. In clinical trials, levosimendan has dose-dependently increased
      cardiac output and decreased pulmonary capillary wedge pressure in patients with
      heart failure. On the other hand, it also increases heart rate and decreases
      blood pressure in these patients. In major clinical trials, where patients with
      decompensated heart failure have been treated with levosimendan, a reduction of
      overall mortality in comparison to placebo or dobutamine has been seen. This
      interesting finding should be verified in prospective outcome trials. In any
      case, the safety of levosimendan during myocardial ischaemia makes this drug
      valuable in the short-term treatment of decompensated heart failure.

PMID- 11322870
TI  - Carvedilol versus other beta-blockers in heart failure.
AB  - Carvedilol is a beta-blocker with ancillary properties. Pilot clinical studies
      with carvedilol, added to the standard therapy of digoxin, diuretics and ACE
      inhibitors, showed beneficial effects in mild, moderate and severe heart failure.
      Patients consistently showed improvement in LV ejection fraction and NYHA
      functional class. Subsequently large clinical trials showed decreased morbidity
      and mortality with carvedilol in mild and moderate and more recently, severe
      heart failure. However, there is little or no improvement in exercise tolerance
      with carvedilol. The beneficial effects of carvedilol in heart failure are
      associated with cardiac remodelling. Metoprolol and bisoprolol are selective
      beta(1)-blockers without ancillary properties. Early studies showed benefits with
      metoprolol and bisoprolol in heart failure. Large clinical trials established
      that metoprolol and bisoprolol decreased mortality and morbidity in heart
      failure. In contrast no benefit has been shown with celiprolol, a selective
      beta(1)-blocker and beta(2)-stimulant in heart failure. There is a debate as to
      whether the ancillary properties of carvedilol contribute to its beneficial
      effect in heart failure, making it a better drug to use than metoprolol. Short
      term studies suggested that carvedilol and metoprolol were equivalent in heart
      failure but short-term is probably not an appropriate way to compare the drugs. A
      recent long-term study and study in poor responders to metoprolol, suggest that
      carvedilol may be better than metoprolol in heart failure.

PMID- 11322871
TI  - Solution NMR structure of the cold-shock protein from the hyperthermophilic
      bacterium Thermotoga maritima.
AB  - Cold-shock proteins (Csps) are a subgroup of the cold-induced proteins
      preferentially expressed in bacteria and other organisms on reduction of the
      growth temperature below the physiological temperature. They are related to the
      cold-shock domain found in eukaryotes and are some of the most conserved proteins
      known. Their exact function is still not known, but translational regulation,
      possibly via RNA chaperoning, has been discussed. Here we present the structure
      of a hyperthermophilic member of the Csp family. The NMR solution structure of
      TmCsp from Thermotoga maritima, the hyperthermophilic member of this class of
      proteins, was solved on the basis of 1015 conformational constraints. It contains
      five beta strands combined in two antiparallel beta sheets making up a beta
      barrel structure, in which beta strands 1-4 are arranged in a Greek-key topology.
      The side chain of R2, which is exclusively found in thermophilic members of the
      Csp family, probably participates in a peripheral ion cluster involving residues
      D20, R2, E47 and K63, suggesting that the thermostability of TmCsp is based on
      the peripheral ion cluster around the side chain of R2.

PMID- 11322872
TI  - Activation of pro-astacin. Immunological and model peptide studies on the
      processing of immature astacin, a zinc-endopeptidase from the crayfish Astacus
      astacus.
AB  - To contribute knowledge of the processing and activation of invertebrate
      proteolytic enzymes, we studied the metalloprotease astacin, a digestive enzyme
      from the freshwater crayfish Astacus astacus (decapod crustacean). It is the
      prototype of the protein family of astacins, members of which occur in organisms
      from bacteria to man and are involved in a variety of physiological reactions.
      According to its genomic structure, astacin is produced as a zymogen [Geier, G.,
      Jacob, E., Stocker, W. & Zwilling, R. (1997) Arch. Biochem. Biophys. 337, 300
      307]. To localize and follow the processing of pro-astacin in different parts of
      the digestive tract, we synthesized two peptides covering the pro part of pro
      astacin and raised antibodies against them. In addition, antiserum against the
      whole active astacin was produced. Using immunohistochemical investigation, we
      detected pro-astacin in the F cells of the hepatopancreas and all the way into
      the tubular lumen and the collecting ducts of this gland. Immunoblot assays
      revealed only active astacin, and never pro-astacin, present in the cardiac
      stomach. We conclude from these studies that astacin is secreted into the lumen
      of the hepatopancreatic tubules in its pro form and is activated on its way to
      the stomach. To investigate which of the two endopeptidases found in the
      digestive tract of crayfish, astacin or trypsin, is responsible for cleaving the
      propeptide from pro-astacin, we synthesized different peptides that mimick the
      activation site. MS analysis of the cleavage products of astacin and trypsin
      showed that astacin is capable of catalyzing its own activation. Any contribution
      of trypsin would require the successive action of an aminopeptidase. Substituting
      glycine for arginine at position -1 of the activation site does not prevent
      astacin activity. As most members of the astacin protein family have basic amino
      acid residues in this position, in these cases also astacin-specific cleavage
      would be possible.

PMID- 11322873
TI  - 4-Hydroxyacetophenone monooxygenase from Pseudomonas fluorescens ACB. A novel
      flavoprotein catalyzing Baeyer-Villiger oxidation of aromatic compounds.
AB  - A novel flavoprotein that catalyses the NADPH-dependent oxidation of 4
      hydroxyacetophenone to 4-hydroxyphenyl acetate, was purified to homogeneity from
      Pseudomonas fluorescens ACB. Characterization of the purified enzyme showed that
      4-hydroxyacetophenone monooxygenase (HAPMO) is a homodimer of approximately 140
      kDa with each subunit containing a noncovalently bound FAD molecule. HAPMO
      displays a tight coupling between NADPH oxidation and substrate oxygenation.
      Besides 4-hydroxyacetophenone a wide range of other acetophenones are readily
      converted via a Baeyer-Villiger rearrangement reaction into the corresponding
      phenyl acetates. The P. fluorescens HAPMO gene (hapE) was characterized. It
      encoded a 640 amino-acid protein with a deduced mass of 71 884 Da. Except for an
      N-terminal extension of approximately 135 residues, the sequence of HAPMO shares
      significant similarity with two known types of Baeyer-Villiger monooxygenases:
      cyclohexanone monooxygenase (27-33% sequence identity) and steroid monooxygenase
      (33% sequence identity). The HAPMO sequence contains several sequence motifs
      indicative for the presence of two Rossman fold domains involved in FAD and NADPH
      binding. The functional role of a recently identified flavoprotein sequence motif
      (ATG) was explored by site-directed mutagenesis. Replacement of the strictly
      conserved glycine (G490) resulted in a dramatic effect on catalysis. From a
      kinetic analysis of the G490A mutant it is concluded that the observed sequence
      motif serves a structural function which is of importance for NADPH binding.

PMID- 11322874
TI  - Human placental calreticulin characterization of domain structure and post
      translational modifications.
AB  - The domain organization and the post-translational modifications of human
      placenta calreticulin were analysed by MS in combination with proteolytic
      digestion. Prolonged treatment with trypsin, chymotrypsin, elastase,
      Staphylococcus aureus V8 protease, or proteinase K all led to a 6- to 7-kDa
      decrease in the molecular mass of calreticulin. The decrease was found to be due
      to cleavages in the region around residue 340. In addition, minor fragments
      resulting from secondary cleavages close to the N-terminus were observed, but no
      stable fragments of intermediate size were found. These results show that the C
      domain of calreticulin is susceptible to proteolytic cleavage and that the N- and
      P-domains form a proteolytically stable tight association. A disulfide bridge
      between the first two cysteines was mapped in the N-domain, and the third
      cysteine was found in the reduced form. No post-translational modifications in
      the form of glycosylation or phosphorylation were found. A modified form of
      calreticulin lacking the C-terminal hexapeptide including the KDEL endoplasmic
      reticulum retention sequon was isolated. Such a truncation may point to a
      mechanism that allows escape of calreticulin from the endoplasmic reticulum.

PMID- 11322875
TI  - A paramagnetic species with unique EPR characteristics in the active site of
      heterodisulfide reductase from methanogenic archaea.
AB  - Heterodisulfide reductase (Hdr) from methanogenic archaea is an iron-sulfur
      protein that catalyses the reversible reduction of the heterodisulfide (CoM-S-S
      CoB) of the methanogenic thiol coenzymes, coenzyme M (H-S-CoM) and coenzyme B (H
      S-CoB). In EPR spectroscopic studies with the enzyme from Methanothermobacter
      marburgensis, we have identified a unique paramagnetic species that is formed
      upon reaction of the oxidized enzyme with H-S-CoM in the absence of H-S-CoB. This
      paramagnetic species can be reduced in a one-electron step with a midpoint
      potential of -185 mV but not further oxidized. A broadening of the EPR signal in
      the 57Fe-enriched enzyme indicates that it is at least partially iron based. The
      g values (gxyz = 2.013, 1.991 and 1.938) and the midpoint potential argue against
      a conventional [2Fe-2S]+, [3Fe-4S]+, [4Fe-4S]+ or [4Fe-4S]3+ cluster. This
      species reacts with H-S-CoB to form an EPR silent form. Hence, we propose that
      only a half reaction is catalysed in the presence of H-S-CoM and that a reaction
      intermediate is trapped. This reaction intermediate is thought to be a [4Fe-4S]3+
      cluster that is coordinated by one of the cysteines of a nearby active-site
      disulfide or by the sulfur of H-S-CoM. A paramagnetic species with similar EPR
      properties was also identified in Hdr from Methanosarcina barkeri.

PMID- 11322876
TI  - Human umbilical vein endothelial cells generate leukotriene C4 via microsomal
      glutathione S-transferase type 2 and express the CysLT(1) receptor.
AB  - Certain immunocompetent myeloid cells, such as eosinophils, basophils and mast
      cells, have a large capacity to synthesize the potent proinflammatory and
      spasmogenic mediator leukotriene (LT) C4 via a specific microsomal glutathione S
      transferase (MGST) termed LTC4 synthase (LTC4S). Here, we report that MGST2, a
      distant homologue of LTC4S, is abundantly expressed in Human umbilical vein
      endothelial cells (HUVEC) and converts LTA4 into a single product, LTC4. Thus,
      using Northern blot, RT-PCR, Western blot, and enzyme activity assays, we show
      that MGST2 is the main, if not the only, enzyme that converts LTA4 into LTC4 in
      membrane preparations of HUVEC. In fact, we failed to detect any expression of
      LTC4S, MGST1 or MGST3 in these cells, indicating that MGST2 is a critical enzyme
      for transcellular LTC4 biosynthesis in the vascular wall. Unlike LTC4S, MGST2
      prefers the naturally occurring free acid of LTA4 over the methyl ester as
      substrate and is also susceptible to product inhibition with an IC50 of about 1
      microM for LTC4. Moreover, HUVEC were found to express the CysLT1 receptor in
      line with a paracrine and autocrine role for cysteinyl-leukotrienes in
      endothelial cell function.

PMID- 11322877
TI  - Characterization of a functional serum response element in the Actin403 gene
      promoter from the crustacean Artemia franciscana.
AB  - The serum response factor (SRF) activates expression of several genes in response
      to growth factors present in serum. SRF also regulates the expression of tissue
      specific genes, including those in vertebrate muscles. An SRF-binding site (CArG
      box) present in the Artemia franciscana Actin403 promoter was shown to be
      necessary for transcriptional activity in cultured cells from Drosophila
      melanogaster and mammals. This DNA region bound mammalian and Drosophila SRFs in
      vitro and mediated transcriptional activation of the Actin403 promoter in
      response to serum, phorbol esters and lysophosphatidic acid in transfected
      cultured mammalian cells. Mutations in the CArG box greatly reduced promoter
      activity and stimulation by extracellular compounds.

PMID- 11322878
TI  - Self-assembled pearling structure of long duplex DNA with histone H1.
AB  - We report that complexes of giant DNA molecules with histone H1 proteins form a
      pearl necklace-like structure when the complexes are prepared by natural dilution
      from a high-salt solution (2 M NaCl) to a low-salt solution (0.2 M and 50 mM
      NaCl). We performed real-time observations on the conformational changes of
      individual T4 phage DNA (166 kb) molecules in bulk solution by fluorescence
      microscopy. To identify H1-binding regions on individual DNA molecules, we also
      performed immunofluorescence microscopic observations on the DNA-H1 complex
      spread on a glass surface. It was found that histone H1 binds DNA in a highly co
      operative manner and is accompanied by local folding of the DNA. On the basis of
      the experimental observations and a theoretical simulation, we propose a self
      assembling mechanism for the pearling structure.

PMID- 11322879
TI  - Pfnek-1, a NIMA-related kinase from the human malaria parasite Plasmodium
      falciparum Biochemical properties and possible involvement in MAPK regulation.
AB  - We have cloned Pfnek-1, a gene encoding a novel protein kinase from the human
      malaria parasite Plasmodium falciparum. This enzyme displays maximal homology to
      the never-in-mitosis/Aspergillus (NIMA)/NIMA-like kinase (Nek) family of protein
      kinases, whose members are involved in eukaryotic cell division processes.
      Similar to other P. falciparum protein kinases and many enzymes of the NIMA/Nek
      family, Pfnek-1 possesses a large C-terminal extension in addition to the
      catalytic domain. Bacterially expressed recombinant Pfnek-1 protein is able to
      autophosphorylate and phosphorylate a panel of protein substrates with a
      specificity that is similar to that displayed by other members of the NIMA/Nek
      family. However, the FXXT motif usually found in NIMA/Nek protein kinases is
      substituted in Pfnek-1 by a SMAHS motif, which is reminiscent of a MAP/ERK kinase
      (MEK) activation site. Mutational analysis indicates that only one of the serine
      residues in this motif is essential for Pfnek-1 kinase activity in vitro. We show
      (a) that recombinant Pfnek-1 is able to specifically phosphorylate Pfmap-2, an
      atypical P. falciparum MAPK homologue, in vitro, and (b) that coincubation of
      Pfnek-1 and Pfmap-2 results in a synergistic increase in exogenous substrate
      labelling. This suggests that Pfnek-1 may be involved in the modulation of MAPK
      pathway output in malaria parasites. Finally, we demonstrate that recombinant
      Pfnek-1 can be used in inhibition assays to monitor the effect of kinase
      inhibitors, which opens the way to the screening of chemical libraries aimed at
      identifying potential new antimalarials.

PMID- 11322880
TI  - Carbohydrate binding properties of banana (Musa acuminata) lectin I. Novel
      recognition of internal alpha1,3-linked glucosyl residues.
AB  - Examination of lectins of banana (Musa acuminata) and the closely related
      plantain (Musa spp.) by the techniques of quantitative precipitation, hapten
      inhibition of precipitation, and isothermal titration calorimetry showed that
      they are mannose/glucose binding proteins with a preference for the alpha
      anomeric form of these sugars. Both generate precipitin curves with branched
      chain alpha-mannans (yeast mannans) and alpha-glucans (glycogens, dextrans, and
      starches), but not with linear alpha-glucans containing only alpha1,4- and
      alpha1,6-glucosidic bonds (isolichenan and pullulan). The novel observation was
      made that banana and plantain lectins recognize internal alpha1,3-linked glucosyl
      residues, which occur in the linear polysaccharides elsinan and nigeran.
      Concanavalin A and lectins from pea and lentil, also mannose/glucose binding
      lectins, did not precipitate with any of these linear alpha-glucans. This is, the
      authors believe, the first report of the recognition of internal alpha1,3
      glucosidic bonds by a plant lectin. It is possible that these lectins are present
      in the pulp of their respective fruit, complexed with starch.

PMID- 11322881
TI  - Carbohydrate binding properties of banana (Musa acuminata) lectin II. Binding of
      laminaribiose oligosaccharides and beta-glucans containing beta1,6-glucosyl end
      groups.
AB  - This paper extends our knowledge of the rather bizarre carbohydrate binding
      poperties of the banana lectin (Musa acuminata). Although a glucose/mannose
      binding protein which recognizes alpha-linked gluco-and manno-pyranosyl groups of
      polysaccharide chain ends, the banana lectin was shown to bind to internal 3-O
      alpha-D-glucopyranosyl units. Now we report that this lectin also binds to the
      reducing glucosyl groups of beta-1,3-linked glucosyl oligosaccharides (e.g.
      laminaribiose oligomers). Additionally, banana lectin also recognizes beta1,6
      linked glucosyl end groups (gentiobiosyl groups) as occur in many fungal
      beta1,3/1,6-linked polysaccharides. This behavior clearly distinguishes the
      banana lectin from other mannose/glucose binding lectins, such as concanavalin A
      and the pea, lentil and Calystegia sepium lectins.

PMID- 11322882
TI  - Conformational model for the consensus V3 loop of the envelope protein gp120 of
      HIV-1 in a 20% trifluoroethanol/water solution.
AB  - Based on experimental NMR data, a model was generated for the conformation of the
      disulfide-bond-closed cyclic peptide corresponding to the whole V3 loop of the
      consensus HIV-1 strain in a 20% trifluoroethanol/water solution. The obtained
      family of structures shows a prominent and well-defined amphipathic alpha helix
      at the C-terminal end of the peptide from Thr23 to Gln32. A series of turns
      characterizes the central Gly15-Tyr21 region, while the N-terminal region is
      poorly defined. Independent experimental data confirms the features of this
      model, and suggests that this type of conformation can be readily adopted when
      the V3 loop is in contact with a membrane. The examined V3 loop belongs to a
      macrophage tropic strain, and using the model, a structural explanation is
      proposed for the different requirements of V3 loops belonging to macrophage and T
      cell line tropic HIV-1 strains.

PMID- 11322883
TI  - Identification and localization of three photobinding sites of
      iodoarylazidoprazosin in hamster P-glycoprotein.
AB  - P-glycoprotein is an ATP-dependent drug-efflux pump which can transport a diverse
      range of structurally and functionally unrelated substrates across the plasma
      membrane. Overexpression of this protein may result in multidrug resistance and
      is a major cause of the failure of cancer chemotherapy. The most commonly used
      photoreactive substrate is iodoarylazidoprazosin. Its binding domains within the
      P-glycoprotein have so far been inferred from indirect methods such as epitope
      mapping. In this study, the binding sites were refined and relocalized by direct
      analysis of photolabeled peptides. P-glycoprotein-containing plasma membrane
      vesicles of Chinese hamster ovary B30 cells were photoaffinity-labeled with
      iodoarylazidoprazosin. After chemical cleavage behind tryptophan residues or
      enzymatic cleavage behind lysine residues, the resulting 125I-labeled peptides
      were separated by tricine/PAGE and HPLC and subjected to Edman sequencing. The
      major photoaffinity binding sites of iodoarylazidoprazosin were localized in the
      amino-acid regions 248-312 [transmembrane segment (TM)4 to TM5], 758-800 (beyond
      TM7 to beyond TM8) and 1160-1218 (after the Walker A motif of the second
      nucleotide-binding domain). Therefore the binding pocket of iodoarylazidoprazosin
      is made up of at least three binding epitopes.

PMID- 11322884
TI  - Purification and characterization of acharan sulfate lyases, two novel
      heparinases, from Bacteroides stercoris HJ-15.
AB  - Two novel acharan sulfate lyases (ASL1 and ASL2: no EC number) have been purified
      from Bacteroides stercoris HJ-15 which was isolated from human intestinal
      bacteria with glycosaminoglycan (GAG) degrading enzymes. These enzymes were
      purified to apparent homogeneity by a combination of QAE-cellulose, DEAE
      cellulose, carboxymethyl-Sephadex C-50, hydroxyapatite and HiTrap SP Sephadex C
      25 column chromatography with the final specific activity of 50.5 and 76.7
      micromol.min-1.mg-1, respectively. Both acharan sulfate lyases are single
      subunits of 83 kDa by SDS/PAGE and gel filtration. ASL1 showed optimal activity
      at pH 7.2 and 45 degrees C. ASL1 activity was inhibited by Cu2+, Ni2+ and Co2+,
      but ASL2 activity was inhibited by Cu2+, Ni2+and Pb2. Both enzymes were slightly
      inhibited by some agents that modify histidine and cysteine residues, but
      activated by reducing agents such as DL-dithiothreitol and 2-mercaptoethanol.
      Both purified bacteroidal acharan sulfate lyases acted to the greatest extent on
      acharan sulfate, and to a lesser extents on heparan sulfate and heparin. They did
      not act on de-O-sulfated acharan sulfate. These findings suggest that the
      biochemical properties of these purified acharan sulfate lyases are different
      from those of the previously purified heparin lyases, but these enzymes belong to
      heparinase II.

PMID- 11322885
TI  - Cloning and characterization of a novel serine/threonine protein kinase gene
      expressed predominantly in developing brain.
AB  - We have isolated a rat gene, sbk, that encodes a novel serine/threonine protein
      kinase possessing a consensus sequence for an SH3-binding domain from developing
      rat brain. Rat SBK comprises 417 amino-acid residues consisting of a
      serine/threonine protein kinase consensus sequence followed by a C-terminal
      proline-rich region. Sequence comparison with other known kinases revealed that
      sbk belongs to a novel family of serine/threonine protein kinases structurally
      related to a Xenopus gastrula-specific protein kinase, Pk9.7. An in vitro kinase
      assay demonstrated that the SBK protein autophosphorylates at serine/threonine
      residues. Transcripts of sbk were strongly detected in brain, and the
      distribution shows an association with neurons but not glial cells. A marked
      increase in sbk transcripts was observed in developing brain in the late
      embryonic stage when dramatic neuronal proliferation, migration, and maturation
      occur. Fluorescence in situ hybridization analysis was used to map sbk to mouse
      chromosome 7F1-F3 and rat chromosome 1q21. These data suggest a role for SBK in
      signal-transduction pathways related to the control of brain development.

PMID- 11322886
TI  - Structure of the H subunit of the photosynthetic reaction center from the
      thermophilic purple sulfur bacterium, Thermochromatium tepidum Implications for
      the specific binding of the lipid molecule to the membrane protein complex.
AB  - The photosynthetic reaction center (RC) is a transmembrane protein complex that
      catalyzes light-driven electron transport across the photosynthetic membrane. The
      complete amino-acid sequence of the H subunit of the RC from a thermophilic
      purple sulfur bacterium, Thermochromatium tepidum, has been determined for the
      first time among purple sulfur bacteria. The H subunit consists of 259 amino
      acids and has a molecular mass of 28 187. The deduced amino-acid sequences of
      this H subunit showed a significant (40%) degree of identity with those from
      mesophilic purple nonsulfur bacteria. The determined primary structure of the H
      subunit was compared with the structures of mesophilic B. viridis and R.
      sphaeroides based on the three-dimensional structure of the H subunit from T.
      tepidum, which has been recently determined by X-ray crystallography. One lipid
      molecule was found in the crystal structure of the T. tepidum RC, and the head
      group of the lipid appears to be stabilized by the electrostatic interactions
      with the conserved basic residues in the H subunit. The above comparison has
      suggested the existence of a lipid-binding site on the molecular surface at which
      a lipid molecule can interact with the RC in a specific manner.

PMID- 11322887
TI  - Regulation of human and mouse procathepsin E gene expression.
AB  - Cathepsin E is an intracellular aspartic proteinase that is considered to have a
      number of physiological roles including antigen processing. Quantitation of
      procathepsin E mRNA by LightCyclertrade mark technology indicated that the gene
      was transcribed in lung but not in kidney of both human and mouse origin. In
      contrast, the transcript was present in mouse spleen and alveolar macrophages but
      not in the counterpart tissue/cells from humans. Regulation of human and mouse
      procathepsin E gene expression was shown not to be influenced by the extent of
      CpG methylation but depended on the recognition of potential binding motifs in
      each promoter region by transcription factors such as GATA1, PU1 and YY1, as
      revealed by functional analysis using a series of promoter/luciferase reporter
      gene fusion constructs. Thus the extent to which the procathepsin E gene is
      expressed in a particular cell type may depend on the balance between the effects
      produced by positive-acting, cell-specific transcription factors such as GATA1
      and PU1 and the negative influence of the ubiquitous YY1 factor. In this way, the
      relative abundance and influence of general and cell-specific transcription
      factors can govern the production of cathepsin E and thereby account for the
      sporadic cell and tissue distribution of this enzyme in different species.

PMID- 11322888
TI  - Secreted aspartic proteases of Candida albicans, Candida tropicalis, Candida
      parapsilosis and Candida lusitaniae. Inhibition with peptidomimetic inhibitors.
AB  - The frequency of Candida infections has increased in recent years and it has been
      accompanied by a significant rise in morbidity and mortality. The secretion of
      aspartic proteases by Candida spp. was demonstrated to be one of the virulence
      determinants. Candida albicans is classified as the major human pathogen in the
      genus Candida. However, other species of this genus have been found to cause an
      increasing number of candidiases. We isolated secreted aspartic proteases (Saps)
      of C. albicans (Sap2p), C. tropicalis (Sapt1p), C. parapsilosis (Sapp1p), and C.
      lusitaniae (Saplp) from culture media. All the isolated proteases were N
      terminally sequenced. Their specific proteolytic activities and sensitivity to
      series of peptidomimetic inhibitors modified in the type of scissile bond
      replacement as well as in the N- and C-termini were analyzed. The most divergent
      substrate specificity was observed for the Sap of C. tropicalis. The specificity
      of Sap of C. lusitaniae is most closely related to that of Sap of C.
      parapsilosis. We designed and prepared an inhibitor containing phenylstatine
      isoster that was equipotent towards all four proteases within the range of 10-10
      10-9 M. The HIV-1 protease inhibitors ritonavir, saquinavir, indinavir, and
      nelfinavir were also tested for the inhibition of four Saps. Only ritonavir and
      saquinavir inhibited Sap2p, Sapt1p, Sapp1p, and Saplp in micromolar
      concentrations.

PMID- 11322889
TI  - Purification and cloning of chloroplast 6-phosphogluconate dehydrogenase from
      spinach. Cyanobacterial genes for chloroplast and cytosolic isoenzymes encoded in
      eukaryotic chromosomes.
AB  - Previous attempts to purify chloroplast 6-phosphogluconate dehydrogenase
      (cp6PGDH), a key enzyme of the oxidative pentose phosphate pathway, have been
      unsuccessful due to rapid activity loss. An efficient purification protocol was
      developed and the enzyme from spinach leaves was purified 1000-fold to apparent
      homogeneity with a specific activity of 60 U.mg-1. The enzyme is a homodimer with
      subunits of 50 kDa. Antibodies raised against the purified cp6PGDH detected a 53
      kDa protein from a crude extract, indicating alterations during purification.
      Purified cp6PGDH was microsequenced and the corresponding spinach cDNA was cloned
      using PCR techniques and degenerate primers. The cDNA for cytosolic 6PGDH from
      spinach was cloned for comparison. Phylogenetic analysis in the context of
      available homologues from eukaryotes and eubacteria revealed that animal and
      fungal cytosolic 6PGDH sequences are more similar to their homologues from gamma
      proteobacteria, whereas plant 6PGDH is more similar to its cyanobacterial
      homologues. The ancestral gene for higher plant 6PGDH was acquired from the
      antecedent of plastids through endosymbiosis and gene transfer to the nucleus. A
      subsequent gene duplication gave rise to higher plant cytosolic 6PGDH, which
      assumed the function of its pre-existing cytosolic homologue through
      endosymbiotic gene replacement. The protein phylogeny of both 6PGDH and of the
      first enzyme of the oxidative pentose phosphate pathway, glucose-6-phosphate
      dehydrogenase, indicate a surprisingly close relationship between the plant and
      Trypanosoma brucei lineages, suggesting that T. brucei (a relative of Euglena
      gracilis) may be secondarily nonphotosynthetic.

PMID- 11322890
TI  - Cloning and characterization of the cDNA and gene for human epitheliasin.
AB  - Previously, we reported cloning and characterization of the mouse gene,
      epitheliasin. In the present work we cloned the cDNA of the full-length human
      orthologue and characterized its gene including 2 kb of 5' flanking sequence.
      Analysis of epitheliasin gene expression in adult tissues shows that it is
      expressed as 3.4 kb and 2 kb transcripts. The major 3.4 kb transcript is observed
      in the following order: prostate > colon > small intestine > pancreas > kidney >
      lung > liver. Epitheliasin transcripts in fetal tissues are observed only in
      kidney and lung. In situ hybridization analysis of tissues revealed that
      epitheliasin was preferentially expressed in epithelial cells. The gene consists
      of 14 exons and 13 introns based on comparison with its cDNA sequence. In the 5'
      flanking region, we identified two transcription start sites and three CpG
      islands encompassing a number of potential regulatory elements including SP1,
      SREBP, GRE/PRE and ERE. The region upstream of the transcription sites lacks a
      TATA box but contains an initiator-like element as well as a downstream promoter
      like element. In vitro experiments with lymph node carcinoma of prostate (LNCaP)
      cells revealed that the epitheliasin gene was induced by androgens and the
      induction was not blocked by cycloheximide indicating that the induction required
      no intermediate protein factors. Immunoprecipitation analysis showed that
      androgens strongly increased epitheliasin protein levels.

PMID- 11322891
TI  - Molecular cloning and functional expression of rat liver cytosolic acetyl-CoA
      hydrolase.
AB  - A cytosolic acetyl-CoA hydrolase (CACH) was purified from rat liver to
      homogeneity by a new method using Triton X-100 as a stabilizer. We digested the
      purified enzyme with an endopeptidase and determined the N-terminal amino-acid
      sequences of the two proteolytic fragments. From the sequence data, we designed
      probes for RT-PCR, and amplified CACH cDNA from rat liver mRNA. The CACH cDNA
      contains a 1668-bp ORF encoding a protein of 556 amino-acid residues (62 017 Da).
      Recombinant expression of the cDNA in insect cells resulted in overproduction of
      functional acetyl-CoA hydrolase with comparable acyl-CoA chain-length specificity
      and Michaelis constant for acetyl-CoA to those of the native CACH. Database
      searching shows no homology to other known proteins, but reveals high
      similarities to two mouse expressed sequence tags (91% and 93% homology) and
      human mRNA for KIAA0707 hypothetical protein (50% homology) of unknown function.

PMID- 11322892
TI  - The structure of the lipopolysaccharide O-antigen produced by Flavobacterium
      psychrophilum (259-93).
AB  - Flavobacterium psychrophilum, a Gram-negative bacterium, is the etiological agent
      of rainbow trout fry syndrome and bacterial cold water disease, septicemic
      infections in reared salmonids. In humans Flavobacterium spp. have been
      associated with neonatal meningitis and septicemia, catheter-associated
      bacteremia, and pneumonia. Recently, several F. psychrophilum surface molecules,
      including lipopolysaccharide (LPS), have been implicated in its pathogenesis and
      identified as potential vaccine and diagnostic candidate macromolecules. Studies
      on the LPS produced by the bacterium are reported herein. The structure of the
      antigenic O-polysaccharide contained in the LPS of F. psychrophilum was deduced
      by the application of analytical NMR spectroscopy, mass spectrometry, glycose and
      methylation analysis, and partial hydrolysis degradations, and was found to be an
      unbranched polymer of trisaccharide repeating units composed of L-rhamnose (L
      Rhap), 2-acetamido-2-deoxy-L-fucose (L-FucpNAc) and 2-acetamido-4-((3S,5S)-3,5
      dihydroxyhexanamido)-2,4-dideoxy-D-quinovose (D-Quip2NAc4NR, 2-N-acetyl-4-N
      ((3S,5S)-3,5-dihydroxyhexanoyl)-D-bacillosamine) (1 : 1 : 1) and having the
      structure: -->4)-alpha-L-FucpNAc-(1-->3)-alpha-D-Quip2NAc4NR-(1-->2)- alpha-L
      Rhap-(1--> where R is (3S,5S)-CH3CH(OH)CH2CH(OH)CH2CO-.

PMID- 11322893
TI  - The chondroitin sulfate chain of bikunin-containing proteins in the inter-alpha
      inhibitor family increases in size in inflammatory diseases.
AB  - Inter-alpha-inhibitor (IalphaI) and pre-alpha-inhibitor (PalphaI) are the main
      members of a set of multichain serine proteinase inhibitors. Present in human
      plasma, they may be involved in control of the inflammatory process. They are
      composed of homologous heavy chains (H1 and H2 for IalphaI; H3 for PalphaI)
      covalently linked by a protein-glycosaminoglycan-protein cross-link to bikunin,
      which is a chondroitin 4-sulfate proteoglycan. During the acute-phase response,
      biosynthesis of IalphaI and PalphaI is downregulated and upregulated,
      respectively. In this work, we provide evidence that, in inflammatory diseases,
      the chondroitin sulfate chain of bikunin increases in size proportionally to the
      severity of the inflammatory response. As a consequence, all IalphaI-related
      components that contain bikunin are structurally modified. Therefore, the changes
      in glycosylation of the acute-phase proteins are not restricted to N-linked
      glycans but also affect glycosaminoglycans. The implications of these findings
      are discussed with regard to biosynthesis and biological role, especially the
      anti-inflammatory effects of IalphaI-related proteinase inhibitors.

PMID- 11322894
TI  - N-Terminally extended human ubiquitin-conjugating enzymes (E2s) mediate the
      ubiquitination of RING-finger proteins, ARA54 and RNF8.
AB  - We have previously cloned cDNAs encoding the N-terminally extended class III
      human ubiquitin-conjugating enzymes (E2s), UBE2E2 and UBE2E3, the biological
      functions of which are not known. In this study, we performed yeast two-hybrid
      screening for protein(s) interacting with UBE2E2, and two RING-finger proteins,
      ARA54 and RNF8, were identified. Both ARA54, a ligand-dependent androgen receptor
      coactivator, and RNF8 interacted with class III E2s (UBE2E2, UbcH6, and UBE2E3),
      but not with other E2s (UbcH5, UbcH7, UbcH10, hCdc34, and hBendless) in the yeast
      two-hybrid assay. The use of various deletion mutants of UBE2E2 and RING-finger
      proteins and two RING point mutants, ARA54 C(220)S and RNF8 C(403)S, in which the
      RING structure is disrupted, showed that the UBC domain of UBE2E2 and the RING
      domain of these RING-finger proteins were involved in this association. Wild-type
      ARA54 and RNF8, expressed in insect Sf9 cells, catalyzed E2-dependent
      autoubiquitination in vitro, whereas the point mutated proteins showed markedly
      reduced activity. Ubiquitination of wild-type ARA54 and RNF8, expressed in COS-7
      cells, was also observed, and a proteasome inhibitor, MG132, prevented the
      degradation of these wild-type proteins, but was much less effective in
      protecting the RING mutants. Transfection of COS-7 cells with a green fluorescent
      protein chimera showed that RNF8 was localized in the nucleus, and ARA54 in both
      the cytoplasm and nucleus. Our results suggest that ARA54 and RNF8 possibly act
      as Ub-ligases (E3) in the ubiquitination of certain nuclear protein(s).

PMID- 11322895
TI  - Subsite specificity of trypanosomal cathepsin L-like cysteine proteases. Probing
      the S2 pocket with phenylalanine-derived amino acids.
AB  - The S2 subsite of mammalian cysteine proteinases of the papain family is
      essential for specificity. Among natural amino acids, all these enzymes prefer
      bulky hydrophobic residues such as phenylalanine at P2. This holds true for their
      trypanosomal counterparts: cruzain from Trypanosoma cruzi and congopain from T.
      congolense. A detailed analysis of the S2 specificity of parasitic proteases was
      performed to gain information that might be of interest for the design of more
      selective pseudopeptidyl inhibitors. Nonproteogenic phenylalanyl analogs (Xaa)
      have been introduced into position P2 of fluorogenic substrates dansyl-Xaa-Arg
      Ala-Pro-Trp, and their kinetic constants (Km, kcat/Km) have been determined with
      congopain and cruzain, and related host cathepsins B and L. Trypanosomal cysteine
      proteases are poorly stereoselective towards D/L-Phe, the inversion of chirality
      modifying the efficiency of the reaction but not the Km. Congopain binds
      cyclohexylalanine better than aromatic Phe derivatives. Another characteristic
      feature of congopain compared to cruzain and cathepsins B and L was that it could
      accomodate a phenylglycyl residue (kcat/Km = 1300 mM-1.s-1), while lengthening of
      the side chain by a methylene group only slightly impaired the specificity
      constant towards trypanosomal cysteine proteases. Mono- and di-halogenation or
      nitration of Phe did not affect Km for cathepsin L-like enzymes, but the presence
      of constrained Phe derivatives prevented a correct fitting into the S2 subsite. A
      model of congopain has been built to study the fit of Phe analogs within the S2
      pocket. Phe analogs adopted a positioning within the S2 pocket similar to that of
      the Tyr of the cruzain/Z-Tyr-Ala-fluoromethylketone complex. However,
      cyclohexylalanine has an energetically favorable chair-like conformation and can
      penetrate deeper into the subsite. Fitting of modeled Phe analogs were in good
      agreement with kinetic parameters. Furthermore, a linear relationship could be
      established with logP, supporting the suggestion that fitting into the S2 pocket
      of trypanosomal cysteine proteases depends on the hydrophobicity of Phe analogs.

PMID- 11322896
TI  - Pressure-exploration of the 33-kDa protein from the spinach photosystem II
      particle.
AB  - The 33-kDa protein isolated from the spinach photosystem II particle is an ideal
      model to explore high-pressure protein-unfolding. The protein has a very low free
      energy as previously reported by chemical unfolding studies, suggesting that it
      must be easy to modulate its unfolding transition by rather mild pressure.
      Moreover, the protein molecule consists of only one tryptophan residue (Trp241)
      and eight tyrosine residues, which can be conveniently used to probe the protein
      conformation and structural changes under pressure using either fluorescence
      spectroscopy or fourth derivative UV absorbance spectroscopy. The different
      experimental methods used in the present study indicate that at 20 degrees C and
      pH 6, the 33-kDa protein shows a reversible two-state unfolding transition from
      atmospheric pressure to about 180 MPa. This value is much lower than those found
      for the unfolding of most proteins studied so far. The unfolding transition
      induces a large red shift of the maximum fluorescence emission of 34 nm (from 316
      nm to 350 nm). The change in standard free energy (DeltaGo) and in volume
      (DeltaV) for the transition at pH 6.0 and 20 degrees C are -14.6 kJ.mol-1 and 
      120 mL.mol-1, respectively, in which the DeltaGo value is consistent with that
      obtained by chemical denaturation. We found that pressure-induced protein
      unfolding is promoted by elevated temperatures, which seem largely attributed to
      the decrease in the absolute value of DeltaGo (only a minor variation was
      observed for the DeltaV value). However, the promotion of the unfolding by
      alkaline pH seems mainly related to the increase in DeltaV without any
      significant changes in DeltaGo. It was also found that NaCl significantly
      protects the protein from pressure-induced unfolding. In the presence of 1 M
      NaCl, the pressure needed to induce the half-unfold of the protein is shifted to
      a higher value (shift of 75 MPa) in comparison with that observed without NaCl.
      Interestingly, in the presence of NaCl, the value of DeltaV is significantly
      reduced whilst that of DeltaGo remains as before. The unfolding-refolding
      kinetics of the protein has also been studied by pressure-jump, in which it was
      revealed that both reactions are a two-state transition process with a relatively
      slow relaxation time of about 102 s.

PMID- 11322898
TI  - Power Doppler myocardial contrast echocardiography using an improved multiple
      frame triggered Harmonic Angio technique.
AB  - Although B-mode harmonic, intermittent-triggered myocardial contrast
      echocardiography (MCE) is a well-established technique, a variety of MCE
      techniques have been introduced recently to improve myocardial opacification. One
      such technique uses a power Doppler method in conjunction with multiple frame
      triggering (MFT), but has been limited by nonuniform microbubble destruction and
      blooming as well as motion artifacts. Utilizing two different contrast agents,
      Definity and Optison, we tested the feasibility of an improved version of
      Harmonic Angio MFT that utilizes a lower transmit frequency, reduced packet size,
      and more stringent wall filter in normal volunteers and in patients with known
      perfusion defects. The results showed that Harmonic Angio MFT produced fill
      frames with readily visible opacification and destruction frames with little
      visible opacification. The patterns of opacification also correlated with the
      expected perfusion patterns in both groups of subjects. Thus, Harmonic Angio MFT
      appears to be a promising new MCE technique.

PMID- 11322899
TI  - The use of transesophageal echocardiography monitoring of transcatheter closure
      of a persistent ductus arteriosus.
AB  - We performed transesophageal echocardiography (TEE) with pediatric biplane probes
      throughout the procedure of transcatheter closure of the ductus arteriosus in 42
      out of 46 patients who were scheduled for this intervention. Patient ages ranged
      from 15 months to 14 years and body weight from 9-53 kg. Both Rashkind double
      umbrella devices and coils were used. The described approach resulted in fewer
      contrast injections and was helpful in monitoring the procedure and in deciding
      when to release the device. To the best of our knowledge this is the first report
      describing a large series where continuous monitoring of transcatheter ductus
      closure was combined with x-ray fluoroscopy and TEE.

PMID- 11322897
TI  - Identification and molecular structural prediction analysis of a toxicity
      determinant in the Bacillus sphaericus crystal larvicidal toxin.
AB  - The operon containing the genes encoding the subunits of the binary crystal toxin
      of Bacillus sphaericus strain LP1-G, BinA and BinB (41.9 kDa and 51.4 kDa,
      respectively), was cloned and sequenced. Purified crystals were not toxic to
      Culex pipiens larvae. Comparison of the amino-acid sequences of this strain
      (Bin4) with those of the three other known toxin types (Bin1, Bin2 and Bin3)
      revealed mutations at six positions, including a serine at position 93 of BinA4,
      whereas all other types of BinA toxin from B. sphaericus had a leucine at this
      position. Reciprocal site-directed mutagenesis was performed to replace this
      serine in BinA4 from LP1-G with a leucine and the leucine in the BinA2 protein
      from strain 1593 with a serine. Native and mutated genes were cloned and
      overexpressed. Inclusion bodies were tested on C. pipiens larvae. Unlike the
      native Bin4 toxin, the mutated protein was toxic, and the reciprocal mutation in
      Bin2 led to a significant loss of toxicity. In vitro receptor-binding studies
      showed similar binding behaviour for native and mutated toxins. In the absence of
      any experimental data on the 3D structure of these proteins, sequence analysis
      and secondary-structure predictions were performed. Amino acid 93 of the BinA
      polypeptide probably belongs to an alpha helix that is sensitive to amino-acid
      modifications. Position 93 may be a key element in the formation of the BinA-BinB
      complex responsible for the toxicity and stability of B. sphaericus Bin toxins.

PMID- 11322900
TI  - Intravascular ultrasound-guided percutaneous balloon angioplasty for membranous
      obstruction of the inferior vena cava.

PMID- 11322901
TI  - Two- and three-dimensional TEE differentiation of lymphoma involving the atrial
      septum from lipomatous hypertrophy.
AB  - In this case report we present two-dimensional (2-D) and three-dimensional (3-D)
      transesophageal echocardiographic (TEE) findings of a patient with lipomatous
      atrial septal hypertrophy and a patient with Hodgkin's lymphoma with atrial
      septal involvement. The echocardiographic characteristics that differentiate
      these two lesions are discussed.

PMID- 11322902
TI  - Therapeutic ultrasound, part I.

PMID- 11322903
TI  - Ultrasound as treatment for coronary artery disease.
AB  - Therapeutic ultrasound is already established in the treatment of diverse
      surgical conditions, such as cataract, liver cancer, and stones, without danger
      to healthy tissue. Clinical trials of catheter-delivered, high energy, low
      frequency (kHz) ultrasound undertaken over the last decade have demonstrated the
      safety of ultrasound in the treatment of peripheral and coronary artery disease,
      and have identified a number of indications in which it may be particularly
      advantageous. The dispersal of thrombus, the recanalization of chronic total
      occlusions, and the favorable modification of the distensibility of small,
      atherosclerotic vessels are three promising areas. The authors review
      developments in these fields.

PMID- 11322904
TI  - Therapeutic ultrasound for chronic total coronary artery occlusions.
AB  - This article focuses on the use of catheter-delivered ultrasound as a device for
      treatment of coronary arterial total occlusion (CTO). The standard treatment of
      CTO is reviewed and serves as the basis for the need for new treatment options,
      such as catheter-delivered ultrasound (SONICROSS). The results of FDA-approved
      Phase I and Phase II clinical trials using SONICROSS for refractory CTO are
      described. The Phase II trials indicate that the SONICROSS-facilitated guidewire
      passage in 71% of CTOs are otherwise refractory to guidewire passage. However, at
      present, the SONICROSS catheter system is limited in its ability to be delivered
      reliably to the CTO because of catheter size and trackability.

PMID- 11322905
TI  - Catheter-delivered ultrasound therapy for native coronary arterial thrombosis and
      occluded saphenous vein grafts.
AB  - Acute coronary thrombosis, overlying ruptured atherosclerotic plaque, is the
      hallmark of myocardial infarction and unstable angina. Despite use of modern
      therapeutic modalities, including glycoprotein IIb/IIIa antagonists and stenting,
      intracoronary thrombus heralds an increased risk of serious complications
      following percutaneous coronary interventions (PCI). Abundant in vitro and in
      vivo experimental data have proven that ultrasound energy is capable of lysing
      intravascular thrombus without injuring the vessel wall. Expanding experience and
      technological advancements now allow us to use this tool in clinical practice. In
      this article we review the emergence of percutaneous ultrasonic thrombolysis as a
      safe and effective tool for treatment of patients in various clinical settings
      associated with coronary thrombosis.

PMID- 11322906
TI  - The use of transducer-tipped ultrasound catheter for recanalization of thrombotic
      arterial occlusions.
AB  - Ultrasound energy is currently being used and intensively investigated for
      recanalization of thrombotically occluded arteries. The ultrasonic energy is
      mainly applied either by a transcutaneous approach or by a percutaneous approach
      through a catheter with an external ultrasound transducer. Catheter-delivered
      transducer-tipped ultrasound thrombolysis is a new and innovative method. In this
      article we summarize the current available data on the use of this new type of
      catheter and discuss future directions and clinical applications.

PMID- 11322907
TI  - Ultrasound-enhanced thrombolysis.
AB  - Problems with current thrombolytic therapy include slow and incomplete
      thrombolysis and frequent bleeding complications. Increasing evidence from in
      vitro, animal, and initial patient studies indicates that application of
      ultrasound as an adjunct to thrombolytic therapy offers unique potential to
      improve effectiveness and decrease bleeding complications. Numerous studies in
      vitro demonstrate that low intensity ultrasound increases enzymatic fibrinolysis
      through mechanisms that include improving drug transport, reversibly altering
      fibrin structure, and increasing tPA binding to fibrin. These observations have
      been confirmed in animal models that demonstrated that ultrasound delivered
      transcutaneously or with an endovascular catheter accelerates thrombolysis in
      models of venous, arterial, and small vessel thrombosis. Ultrasound delivered at
      higher intensities using either an endovascular vibrating wire or
      transcutaneously in conjunction with stabilized microbubbles can cause mechanical
      fragmentation of thrombus without administration of plasminogen activator. Recent
      studies indicate that ultrasound at lower frequencies in the range of 20-40 kHz
      has a greater effect on thrombolysis with improved tissue penetration and less
      heating. These studies form the basis for clinical trials investigating the
      potential of ultrasound as an adjunct to improve thrombolytic therapy.

PMID- 11322908
TI  - Noninvasive transcutaneous low frequency ultrasound enhances thrombolysis in
      peripheral and coronary arteries.
AB  - Previous studies have shown that external ultrasound with low frequencies and
      high intensities can enhance thrombolytic drug-induced clot dissolution during in
      vitro experiments. In this series of studies, we evaluated the efficacy of
      peripheral and coronary thrombolysis in vivo in animals by using noninvasive
      transcutaneous ultrasound combined with thrombolytic drugs (streptokinase and
      tPA) and/or microbubbles agents (dodecafluoropentane [DDFP] and perfluorocarbon
      exposed sonicated dextrose albumin [PESDA]). Thrombotic occlusions were induced
      in 74 rabbit iliofemoral arteries and 24 canine left anterior descending (LAD)
      coronary arteries in this in vivo study. By using the combination of
      transcutaneous ultrasound and streptokinase, the angiographic patency rate in
      rabbit iliofemoral arteries was higher (56%-100%) than with ultrasound (6%; P <
      or = 0.0036) and streptokinase alone (6%; P < or = 0.0012). Also, with
      transcutaneous ultrasound and microbubbles, the angiographic patency rates were
      76%-100% as compared with ultrasound alone (0%, P < or = 0.0003) or microbubbles
      alone (9%, P < or = 0.0001). In the canine study of acute myocardial infarction,
      thrombolysis in myocardial infarction (TIMI) grade flow at 90 minutes in the tPA
      alone group was 0.92 +/- 1.4 as compared with 2.42 +/- 1.9 in the tPA plus
      transthoracic ultrasound group (P = 0.006). There was much improved reperfusion
      with tPA plus ultrasound as compared with tPA alone. In vivo animal studies
      demonstrate that noninvasive transcutaneous ultrasound can greatly enhance the
      effect of clot dissolution with thrombolytic drugs and/or microbubbles, and has
      the potential for clinical application as an adjunctive method to improve
      arterial thrombolysis.

PMID- 11322909
TI  - Potential use of therapeutic ultrasound in ischemic stroke treatment.
AB  - Systemic treatment with rtPA approved for a 3-hour window is the only established
      causal therapy for acute stroke in the United States and Canada. Thrombolytic
      therapy with rtPA demonstrated a small, although significantly reduced morbidity,
      in a limited number of highly selected patients. As recently shown, intraarterial
      application is favorable and opens the window of treatment up to 6 hours. The
      combination of ultrasound with thrombolytic agents may further enhance the
      potential benefit by means of enzymatic-mediated thrombolysis, which has been
      demonstrated in different in vitro and in vivo experiments for an accelerated
      recanalization of occluded peripheral and coronary vessels. Whereas no or only
      small attenuation of ultrasound can be expected through skin and chest, intensity
      will be significantly attenuated if penetration of the skull is required. The
      transcranial penetration of ultrasound increases when the frequency is decreased
      to 20 kHz and may be transmitted through the skull transtemporally with tolerable
      attenuation up to 200 kHz. This results in efficacy in vitro with low intensities
      of 0.5-2.0 W/cm(2) systemic treatment with rtPA approved for a 3-hour window in
      the nonfocused ultrasound field. Application of ultrasound insonation increased
      rtPA-mediated thrombolysis up to 20% in a static model; meanwhile, it enhanced
      the recanalization rate from 30%-90% in a flow model. In vitro results suggest
      that 1 MHz ultrasound with 0.5 W/cm(2), established for diagnostic purposes, may
      already enhance rtPA- mediated thrombolysis. Before therapeutic ultrasound can be
      tested clinically in acute stroke, safety of transcranial exposure of the brain
      has to be confirmed. To date, animal experiments suggested no harm to the blood
      brain barrier or systemic heating with 2 W/cm(2). This combined treatment is one
      perspective in optimizing therapy in acute stroke within the acute phase and may
      be applied easily with few limitations.

PMID- 11322910
TI  - Augmentation of ultrasound-induced clot disruption by nongas-filled
      microparticles.
AB  - The augmentation of ultrasound-induced clot disruption by echocardiographic
      contrast microbubbles may be a direct mechanical erosive effect of the clot by
      the microparticles. To further assess this hypothesis, we evaluated the rate and
      extent of clot disruption by using external ultrasound and nongas-filled
      microparticles (HAEMACCEL and HAES). Human blood clots were used in this in vitro
      study. The percent clot reduction using the combination of ultrasound and
      microparticles was dose dependent and significantly higher than that with
      microparticles alone.

PMID- 11322911
TI  - An Approach to Ostial Lesion Management.

PMID- 11322912
TI  - Management of Atherosclerotic Renal Artery Stenosis: Interventional Versus
      Medical Therapy.
AB  - Atherosclerotic renal artery stenosis (RAS) is the most common secondary cause of
      hypertension, and often results in hypertension that is difficult to control.
      Atherosclerotic RAS may also result in chronic renal insufficiency, and although
      controversial, likely leads to end-stage renal failure in a subset of patients.
      Bilateral RAS, or stenosis to a solitary functioning kidney, has resulted in
      recurrent episodes of "flash" pulmonary edema and unstable angina pectoris.
      Despite these serious sequelae of RAS, there remains no consensus on optimal
      therapy. Invasive therapy (endovascular percutaneous transluminal angioplasty,
      with or without stent deployment; surgical revascularization) has generated
      significant interest among interventional physician specialists. However,
      effective antihypertensive therapy may be a reasonable option in certain
      scenarios.

PMID- 11322913
TI  - Infrapopliteal Endovascular Techniques: Indications, Techniques, and Results.
AB  - The emerging field of endovascular therapy is opening up new therapeutic avenues
      for the treatment of peripheral vascular disease. The infrapopliteal arterial bed
      is a complex vascular bed. Treatment is usually restricted to patients with limb
      threatening ischemia. Although education and medical therapy play a cornerstone
      role in long-term success, endovascular therapy offers a potentially easy low
      risk treatment for early healing of damaged tissue. Surgical therapy remains the
      gold standard of treatment, but there remains significant associated morbidity
      and mortality. A clear understanding of the vascular anatomy, disease process,
      extent of tissue damage and comorbidities is necessary in forming the treatment
      plan for any particular patient. Close follow-up and possible retreatment is a
      key responsibility for the endovascular physician.

PMID- 11322914
TI  - Aortoiliac Occlusive Disease: Surgical Versus Interventional Therapy.
AB  - The treatment of atherosclerotic aortoiliac disease has evolved from surgical
      endarterectomy to aortobifemoral bypass grafting to endovascular balloon
      angioplasty with stenting. Excellent results can be realized with each of these
      techniques in appropriately selected patients. Stenting has broadened the
      applicability of endovascular treatment to patients with iliac occlusions and
      those in need of concomitant infrainguinal bypass. Improvements in surgical care
      have reduced the risk associated with open revascularization. Percutaneous
      endovascular therapy is typically advocated as the initial treatment option,
      reserving bypass surgery for treatment failures--patients with severe ischemia or
      patients with extensive disease, particularly with lesions that extend into the
      common femoral artery.

PMID- 11322915
TI  - Carotid Artery Stent Placement Prior to Coronary Angioplasty or Coronary Bypass
      Graft Surgery.
AB  - Patients with concomitant carotid and coronary artery disease are at high risk of
      both cardiac and cerebrovascular complications when they undergo
      revascularization procedures. The best management strategies for patients with
      concomitant disease have not been determined for certain. Staged surgical
      procedures with either coronary artery bypass grafting prior to carotid
      endarterectomy or vice versa appear to be associated with an increased risk of
      ischemic complications compared to separate procedures. Until recently, there
      were no convincing data favoring a simultaneous or combined revascularization
      approach. Carotid artery stenting has emerged as a treatment option in patients
      with cerebrovascular disease, even in the presence of a high cardiac risk. Recent
      results in patients with severe concomitant coronary artery disease are
      encouraging. This report focuses on the treatment of severe carotid artery
      stenosis by stent implantation in patients with life-threatening comorbidity to
      emphasize the possibility of this endovascular approach as an alternative
      treatment option.

PMID- 11322916
TI  - Femoropopliteal Occlusions: Experience with Peripheral Excimer Laser Angioplasty.
AB  - Long superficial femoral artery occlusions can be recanalized successfully by
      excimer laser-assisted angioplasty with a high technical success rate. To
      maintain a high patency rate, an intensive clinical follow-up is mandatory.
      Nevertheless, performing repeat interventions will provide a relevant improvement
      in quality of life that can be maintained in the majority of patients.

PMID- 11322917
TI  - Optimal Platelet Inhibition for PCI in ACS: Pretreatment, In-laboratory, Both or
      Neither.
AB  - The results of recent trials suggest that an aggressive antiplatelet regimen that
      includes a glycoprotein (GP) IIb/IIIa antagonist, in conjunction with an early
      revascularization strategy, may be the optimal treatment plan for patients
      presenting with a non-ST-elevation acute coronary syndrome (ACS). However,
      whether all patients presenting to the emergency room with a suspected ACS really
      benefit from the addition of a GP IIb/IIIa receptor inhibitor, and in those who
      do, the optimal time to start therapy has not yet been clearly identified.
      Patients with objective evidence of ischemia, especially elevated myocardial
      enzymes, as well as patients on chronic aspirin therapy at the time of their ACS,
      appear to derive the greatest benefit from the addition of a GP IIb/IIIa
      antagonist. Trial results strongly support the use of a GP IIb/IIIa inhibitor at
      the time of a percutaneous coronary intervention in this patient population, but
      starting therapy prior to the procedure is best supported by the data in those
      patients who have refractory ischemia despite good medical therapy, or patients
      who will be medically stabilized for greater than 24 hours.

PMID- 11322918
TI  - Update on Pharmacology for Restenosis.
AB  - Coronary restenosis remains a major limitation of percutaneous coronary
      intervention and has become epidemic in the developed countries. Because almost
      80% of the contemporary interventional procedures are performed with the use of
      coronary stents, strategies aimed at eradicating neointimal hyperplasia are the
      current research focus. Antiproliferative agents, such as rapamycin, tranilast,
      and trapidil, are undergoing phase III clinical trials to determine the efficacy
      of these drugs in preventing restenosis. Stent-based pharmacologic therapy to
      enhance local delivery of the drug has emerged as a promising anti-restenosis
      strategy. This article provides an update on the development of the pharmacologic
      therapy for coronary restenosis.

PMID- 11322919
TI  - Systematic Review of Hirudin in Acute Coronary Syndromes and Percutaneous
      Coronary Intervention.
AB  - Thrombin plays a key role in the pathogenesis of acute coronary syndromes because
      it is a potent platelet agonist and converts fibrinogen to fibrin. Hirudin is a
      powerful, direct, and specific antithrombin agent that can be used in many
      therapeutic scenarios in which heparin is routinely used. In this systemic
      review, we summarize evidence from randomized clinical trials evaluating the
      benefits and risks of recombinant hirudin for the treatment of acute coronary
      syndromes and patients undergoing percutaneous coronary intervention.

PMID- 11322920
TI  - Duct-Occlud for Occlusion of Patent Ductus Arteriosus.
AB  - The Duct-Occlud Occlusion System (ATG Co., Malta, Europe) is the only coil-type
      device that has been specifically designed to close the patent ductus arteriosus
      (PDA). The Duct-Occlud coil has no Dacron feathers. Occlusion of the PDA is
      achieved by precise positioning and implantation of a large number of densely
      packed coils with configuration appropriate for the PDA. A principle feature of
      the delivery system is retrievability, which facilitates both repositioning of a
      suboptimally placed device and exchange for a larger or more appropriate device.
      Standard and reinforced devices are available for closure of PDA with minimum
      diameter up to 4 mm. Clinical studies have demonstrated device safety and
      efficacy.

PMID- 11322921
TI  - Transcatheter PDA Closure Using the Gianturco-Grifka Vascular Occlusion Device.
AB  - Transcatheter interventional procedures for the treatment of congenital heart
      defects have become increasingly important. The patent ductus arteriosus (PDA) is
      a common congenital defect that is amenable to transcatheter occlusion. Several
      transcatheter occlusion devices are available. However, due to different PDA
      shapes and sizes, each device cannot be used to occlude every PDA. Thus, there is
      a need for new safe and effective transcatheter occlusion devices. We developed a
      new transcatheter device, the Gianturco-Grifka Vascular Occlusion Device (GGVOD),
      which consists of a nylon sack attached to an end-hole catheter. A wire is
      advanced through the catheter into the sack. The wire coils, filling the sack,
      occluding the vessel, and providing transmural pressure to maintain the sack
      position. Prior to release, the device may be repositioned, removed, or exchanged
      for a different sized device. The device is available in four sizes. We evaluated
      this device in a canine model, occluding subclavian and carotid arteries, and
      surgically created aortopulmonary shunts. All vessels were occluded completely
      without complication. In children, we have used the device to occlude PDA and
      other vascular anomalies. In every patient, the PDA (or other vessel) was
      occluded completely and without complication. When compared with other occlusion
      devices, this device has several advantages: the ability to reposition the device
      or remove it prior to release, the ability to conform to many vascular shapes,
      and four different sizes. The GGVOD has become another important tool in the
      transcatheter armamentarium.

PMID- 11322922
TI  - Guanidino-containing drugs in cancer chemotherapy: biochemical and clinical
      pharmacology.
AB  - The pharmacology and clinical application of three guanidino-containing compounds
      are reviewed in this commentary with special focus on a new member of this group
      of drugs, CHS 828 [N-(6-(4-chlorophenoxy)hexyl)-N'-cyano-N"-4-pyridylguanidine].
      m-Iodobenzylguanidine (MIBG) and methylglyoxal bis(guanylhydrazone) (MGBG) have
      been extensively studied, preclinically as well as clinically, and have
      established use as anticancer agents. MIBG has structural similarities to the
      neurotransmitter, norepinephrine, and MGBG is a structural analog of the natural
      polyamine spermidine. CHS 828 is a pyridyl cyanoguanidine newly recognized as
      having cytotoxic effects when screening antihypertensive compounds. Apart from
      having the guanidino groups in common, there are many differences between these
      drugs in both structure and their mechanisms of action. However, they all inhibit
      mitochondrial function, a seemingly unique feature among chemotherapeutic drugs.
      In vitro in various cell lines and primary cultures of patient tumor cells and in
      vivo in various tumor models, CHS 828 has cytotoxic properties unlike any of the
      standard cytotoxic drugs with which it has been compared. Among these are non
      cross-resistance to standard drugs and pronounced activity in tumor models
      acknowledged to be highly drug-resistant. Similar to MIBG, CHS 828 induces an
      early increase in extracellular acidification, due to stimulation of the
      glycolytic flux. Furthermore, ATP levels decrease, and the syntheses of DNA and
      protein are shut off after approximately 30 hr of exposure, indicating active
      cell death. CHS 828 is now in early clinical trials, the results of which are
      eagerly awaited.

PMID- 11322924
TI  - Effects of structurally related flavonoids on cell cycle progression of human
      melanoma cells: regulation of cyclin-dependent kinases CDK2 and CDK1.
AB  - We have investigated the effects of a series of flavonoids on cell proliferation
      and cell cycle distribution in human melanoma cells OCM-1. Among the compounds
      that potently inhibited OCM-1 cell proliferation, we show that the presence of a
      hydroxyl group at the 3'-position of the ring B in quercetin and luteolin,
      correlated to a G1 cell cycle arrest while its absence in kaempferol and apigenin
      correlated to a G2 block. Genistein with a hydroxyl at 5-position of the ring A
      arrested cells in G2 while daidzein which lacks it, induced an accumulation of
      cells in G1. We demonstrate that flavonoids, which induced a cell cycle block in
      G1, inhibited the activity of CDK2 by 40-60%. By contrast, those which caused an
      accumulation of cells in G2/M were without effect. On the other hand, while
      quercetin, daidzein and luteolin did not alter the activity of CDK1, kaempferol,
      apigenin and genistein inhibited this kinase by 50-70%. We demonstrate that the
      up-regulation of the CDK inhibitors p27(KIP1) and p21(CIP1) is likely responsible
      for the inhibition of CDK2 while inhibition of CDK1 was rather due to the
      phosphorylation of the kinase on Tyr15 residue.

PMID- 11322923
TI  - Effect of wogonin, a plant flavone from Scutellaria radix, on the suppression of
      cyclooxygenase-2 and the induction of inducible nitric oxide synthase in
      lipopolysaccharide-treated RAW 264.7 cells.
AB  - Plant flavonoids show anti-inflammatory activity both in vitro and in vivo. Some
      flavonoids, such as flavone derivatives, have been reported previously to inhibit
      nitric oxide (NO) production by suppressing inducible nitric oxide synthase
      (iNOS) expression. In this investigation, the effects of wogonin, a potent
      inhibitor of NO production among the flavonoids tested, on cyclooxygenase-2 (COX
      2) induction and activity were elucidated further in connection with iNOS, using
      a mouse macrophage cell line, RAW 264.7. Wogonin inhibited NO and prostaglandin
      E(2) (PGE(2)) production from lipopolysaccharide-induced RAW cells with IC(50)
      values of 31 and 0.3 microM, respectively. When added after the induction of iNOS
      and COX-2, wogonin inhibited the formation of PGE(2) (IC(50) = 0.8 microM), but
      not the production of NO. Wogonin inhibited COX-2 activity directly (IC(50) = 46
      microM) from the homogenate of aspirin-pretreated RAW cells, as determined by
      measuring [(14)C]PGE(2) formation from [(14)C]arachidonic acid. However, it did
      not inhibit iNOS or phospholipase A(2) activity. Western blotting showed that
      wogonin suppressed the induction of both iNOS and COX-2. Prednisolone also
      suppressed the induction of iNOS and COX-2. Whereas RU-486 (a steroid receptor
      antagonist) reversed the suppressive activity of prednisolone, it did not affect
      the suppressive activity of wogonin, suggesting that the suppressive activity of
      wogonin is not mediated by binding to a steroid receptor. Results from the
      present study demonstrated that wogonin is a direct COX-2 inhibitor, as well as
      an inhibitor of iNOS and COX-2 induction. Wogonin may be a potential agent for
      use in the treatment of inflammatory diseases.

PMID- 11322925
TI  - Limitations of the single-cell gel electrophoresis assay to monitor apoptosis in
      U937 and HepG2 cells exposed to 7beta-hydroxycholesterol.
AB  - The single-cell gel electrophoresis (comet) assay is a method which allows the
      detection of DNA strand breaks in individual cells. It has been suggested that
      the single cell gel electrophoresis assay, as an index of DNA fragmentation
      during cell death, may be applied to monitor apoptosis. The aim of the present
      study was to determine if the pattern of DNA fragmentation determined by the
      single cell gel electrophoresis assay can be used to discriminate between the
      mode of cell death in two cell lines (U937, a human monocytic blood cell line and
      HepG2, a human hepatocarcinoma cell line) which were treated with 30 microM 7beta
      hydroxycholesterol (7betaOHC) over a 48 hr period. The single cell gel
      electrophoresis assay was compared with more established methods for the
      determination of apoptosis such as morphological examination, flow cytometry and
      DNA laddering. The percentage of maximally damaged nuclei as measured by the
      single cell gel electrophoresis assay was found to be similar at 48 hr in both
      U937 and HepG2 cells when treated with 7betaOHC. However, morphological
      examination, flow cytometry and DNA laddering techniques showed that 7betaOHC
      induced apoptosis in U937 cells but not in HepG2 cells. Thus, although the
      alkaline single cell gel electrophoresis assay detected DNA strand breaks
      occurring during cell death, these breaks were observed only when the process was
      fairly well advanced and a major part of the cells had lost membrane
      permeability. Therefore the present report demonstrates that the single cell gel
      electrophoresis assay, used in isolation, cannot accurately be used to
      distinguish between the mode of cell death induced by 7betaOHC in U937 cells
      (apoptosis), or HepG2 cells (cell lysis).

PMID- 11322926
TI  - Tight binding of the angiotensin AT(1) receptor antagonist.
AB  - Angiotensin II induces angiotensin AT(1) receptor internalization via Clathrin
      coated pits formation. We investigated whether insurmountable inhibition by the
      non-peptide antagonist 2-ethoxy-1-[(2'-(1H-tetrazol-5-yl) biphenyl-4-yl) methyl]
      1H-benzimidazoline-7-carboxylic acid (candesartan) was related to receptor
      internalization. Mild acid treatment can discriminate between internalized and
      cell surface bound [(3)H]angiotensin II. In contrast, it provides no information
      about the subcellular localization of bound [(3)H]candesartan since this binding
      is acid resistant. The internalization of [(3)H]angiotensin II is rapidly
      inhibited in the presence of 0.4 M sucrose. Yet, no such rapid effect was noticed
      for [(3)H]candesartan. [(3)H]candesartan displays insurmountable/long lasting
      binding to the vast majority of both wild type and L(314) truncated rat
      angiotensin AT(1A) receptors with impaired receptor internalization. In agreement
      with previously published AT(1) angiotensin receptor visualization experiments,
      the present data suggest that non-peptide antagonist-angiotensin AT(1) receptor
      complexes remain at the cell surface. Insurmountable antagonism of candesartan is
      therefore independent from receptor internalization via clathrin-coated pits.

PMID- 11322927
TI  - Structural damage to proteins caused by free radicals: asessment, protection by
      antioxidants, and influence of protein binding.
AB  - Oxidative damage to proteins results in biological dysfunctions such as perturbed
      activity in enzymes, transport proteins, and receptors. Here, we investigated
      structural damage to proteins induced by free radicals. Structural alterations to
      lysozyme, human serum albumin (HSA) and beta-lactoglobulin A were monitored by
      capillary zone electrophoresis. Four well-known antioxidants (quercetin,
      melatonin, Trolox, and chlorogenic acid) were examined for their ability to
      inhibit protein damage and to bind to these proteins. Melatonin and chlorogenic
      acid, which did not bind to any of the three proteins under study, showed
      scavenging and protective activities well correlated with the amount of free
      radicals generated. Trolox, which bound only to HSA, was a better protector of
      HSA than of the two other proteins, indicating that its antioxidant capacity is
      increased by a shielding effect. Finally, quercetin was a good antioxidant in
      protecting lysozyme and beta-lactoglobulin A, but its binding to HSA resulted in
      a pro-oxidant effect that accelerated HSA fragmentation. These results
      demonstrate that binding of an antioxidant to a protein may potentiate protection
      or damage depending on the properties of the antioxidant.

PMID- 11322928
TI  - Alteration of nuclear factor-kappaB (NF-kappaB) expression in bone marrow stromal
      cells treated with etoposide.
AB  - Bone marrow stromal cells are an essential regulatory component in the
      hematopoietic microenvironment. Regulation of hematopoietic cell development is
      mediated, in part, through interaction of progenitor cells with stromal cell
      vascular cell adhesion molecule-1 (VCAM-1). VCAM-1 expression has been shown to
      be driven primarily by binding of nuclear factor-kappaB (NF-kappaB) to two
      consensus binding sites in the promoter region. In this study, we show that down
      regulation of VCAM-1 by the chemotherapeutic agent etoposide (VP-16) is
      associated with altered cellular localization of NF-kappaB. We demonstrated that
      VCAM-1 was diminished at the transcriptional level following treatment of stromal
      cells with VP-16, without alteration of VCAM-1 stability. Culture of bone marrow
      stromal cells in VP-16 resulted in reduced nuclear RelA (p65), a modest increase
      in nuclear NF-kappaB1 (p50), and reduced NF-kappaB binding to its DNA consensus
      sequence. Total levels of the NF-kappaB inhibitor Ikappa-Balpha were reduced
      during exposure to VP-16. Following removal of VP-16 from the culture, p65 and
      p50 nuclear profiles approximated those of untreated stromal cells, and VCAM-1
      protein expression was restored. The current study indicates that NF-kappaB is a
      target molecule that is responsive to VP-16-induced damage in bone marrow stromal
      cells. As the primary transcription factor that promotes VCAM-1 expression, the
      observed changes in p65 and p50 cellular localization during treatment have a
      direct consequence for stromal cell function. The myriad of genes regulated by NF
      kappaB, including both adhesion molecules and cytokines that contribute to
      stromal cell function, make chemotherapy-induced disruption of NF-kappaB
      biologically significant. Alterations in NF-kappaB activity may provide one
      measure by which the effects of aggressive treatment strategies on the bone
      marrow microenvironment can be evaluated.

PMID- 11322929
TI  - Interaction of enkephalins with oxyradicals.
AB  - The interaction of enkephalins (leu-enkephalin and met-enkephalin) and other
      tyrosine amino-terminal peptides with reactive oxygen species has been
      investigated. All the peptides tested exhibited hydroxyl radical and superoxide
      anion scavenging ability and the capacity to reduce the rate of lipid
      peroxidation induced by 2,2'-azobis(2-amidinopropane). The scavenging activity
      was observed in the 0.1-1 mM concentration range. It has been observed that
      enkephalins underwent an oxidative modification by Fenton systems. The tyrosine
      amino-terminal residue was attacked by hydroxyl radical, being converted to dopa.
      The overall transformation produced opiomelanin pigments. This oxidative process
      provides evidence of a possible route for opiomelanin synthesis without any
      enzyme intervention.

PMID- 11322930
TI  - Novel modified adenosine 5'-triphosphate analogues pharmacologically
      characterized in human embryonic kidney 293 cells highly expressing rat brain
      P2Y(1) receptor: Biotinylated analogue potentially suitable for specific P2Y(1)
      receptor isolation.
AB  - Rat brain P2Y(1) (rP2Y(1)) receptor-transfected human embryonic kidney cells (HEK
      293) were recently shown to have enhanced reactivity to both ATP and ADP
      (Vohringer C, Schafer R, Reiser G. Biochem Pharmacol 2000;59:791-800). Here, we
      demonstrated the usefulness of this cell line as a system for further studying
      novel adenine nucleotide analogues (Halbfinger et al. J Med Chem 1999;42:5325-37)
      and for the biochemical characterization of the P2Y(1) receptor. By measurement
      of intracellular Ca(2+) release, for 2-butylthio-, 2-butylamino-, and 2-butyloxy
      ATP (2-BuS-, 2-BuNH-, 2-BuO-ATP), EC(50) values of 1.3, 5, and 60 nM were
      determined, markedly lower than the value for ATP (130 nM). The EC(50) for 2
      BuSADP was 1.1 nM. The corresponding 8-substituted ATP analogues showed a
      substantially lower potency than ATP (ATP > 8-BuSATP > 8-BuNHATP approximately 8
      BuOATP). AMP induced intracellular Ca(2+) release with a very low potency; 2- and
      8-substitutions on AMP caused no significant potency shift, except for 2-BuSAMP
      (EC(50) = 180 nM). Another new P2Y receptor probe, 2-[(6-biotinylamido)
      hexylthio]ATP, was 22-fold more potent than ATP (EC(50) = 6 nM), revealing that
      even more bulky substituents linked to the C-2 position bind with high affinity
      at the P2Y(1) receptor. This biotinylated probe was successfully used for the
      enrichment of the P2Y(1) receptor tagged with green fluorescent protein from a
      crude membrane fraction. This one-step enrichment provides a substantial advance
      for P2Y(1) receptor purification. Thus, human embryonic kidney 293 cells stably
      transfected with the rP2Y(1) receptor represent a powerful model system for
      pharmacological characterization of the P2Y(1) receptor, circumventing problems
      associated with natural systems. They provide a means for the development of
      P2Y(1) ligands of high potency and a good source for obtaining purified P2Y(1)
      receptor.

PMID- 11322931
TI  - Inhibition of glutamate release by BIA 2-093 and BIA 2-024, two novel derivatives
      of carbamazepine, due to blockade of sodium but not calcium channels.
AB  - We investigated the mechanism(s) of action of two new putative antiepileptic
      drugs (AEDs), (S)-(-)-10-acetoxy-10,11-dihydro-5H-dibenz[b,f]azepine-5
      carboxamide (BIA 2-093) and 10,11-dihydro-10-hydroxyimino-5H-dibenz[b,f]azepine-5
      carboxamide (BIA 2-024), by comparing their effects on the release of endogenous
      glutamate in hippocampal synaptosomes, with those of carbamazepine (CBZ) and
      oxcarbazepine (OXC). The AEDs inhibited the release of glutamate evoked by 4
      aminopyridine (4-AP) or veratridine in a concentration-dependent manner, being
      CBZ more potent than the other AEDs. Using conditions of stimulation (30 mM KCl),
      where Na(+) channels are inactivated, the AEDs did not inhibit either the Ca(2+)
      dependent or -independent release of glutamate. The results indicate that BIA 2
      093 and BIA 2-024 have sodium channel-blocking properties, but CBZ and OXC are
      more potent than the new AEDs. Moreover, the present data also indicate that
      Ca(2+) channels coupled to the exocytotic release of glutamate and the activity
      of the glutamate transporter were not affected by the AEDs.

PMID- 11322932
TI  - A dual role of protein kinase C in insulin signal transduction via adenylyl
      cyclase signaling system in muscle tissues of vertebrates and invertebrates.
AB  - Further decoding of a novel adenylyl cyclase signaling mechanism (ACSM) of the
      action of insulin and related peptides detected earlier (Pertseva et al. Comp
      Biochem Physiol B Biochem Mol Biol 1995;112:689-95 and Pertseva et al. Biochem
      Pharmacol 1996;52:1867-74) was carried out with special attention given to the
      role of protein kinase C (PKC) in the ACSM. It was shown for the first time that
      transduction of the insulin signal via the ACSM followed by adenylyl cyclase (AC,
      EC 4.6.1.1) activation was blocked in the muscle tissues of rat and mollusc
      Anodonta cygnea in the presence of pertussis toxin, inducing the impairment of
      G(i)-protein function, wortmannin, an inhibitor of phosphatidylinositol 3-kinase
      (PI3-K), and calphostin C, a blocker of PKC. The cholera toxin treatment of
      muscle membranes led to an increase in basal AC activity and a decrease in enzyme
      insulin reactivity. Phorbol ester and diacylglycerol activation of PKC (acute
      treatment) induced the inhibition of the insulin AC activating effect. This
      negative influence was also observed in the case of the AC system activated by
      biogenic amines. It was first concluded that the ACSM of insulin action involves
      the following signaling chain: receptor tyrosine kinase => G(i) (betagamma) =>
      PI3-K => PKCzeta (?) => G(s) => AC => adenosine 3',5'-cyclic monophosphate. It
      was also concluded that the PKC system has a dual role in the ACSM: (1) a
      regulatory role (PKC sensitive to phorbol esters) that is manifested as a
      negative feedback modulation of insulin signal transduction via the ACSM; (2) a
      transductory role, which consists in direct participation of atypical PKC
      (PKCzeta) in the process of insulin signal transduction via the ACSM.

PMID- 11322933
TI  - Effects of epidermal growth factor on CYP inducibility by xenobiotics, DNA
      replication, and caspase activations in collagen I gel sandwich cultures of rat
      hepatocytes.
AB  - In this study, we investigated the combined effects of EGF and collagen I gel on
      the phenotype of cultured rat hepatocytes and we focussed our investigations on
      the regulation of xenobiotic-mediated induction of CYP, cell cycle progression
      and activation of capases 8 and 3. We found that EGF, added to basal culture
      medium or phenobarbital (3.2 mM) containing medium, provoked a moderate decrease
      of CYP1A1 and CYP2B1/2 activities. However, EGF did not exert any inhibitory
      effect on 3-methylcholantrene (5 microM) and beta-naphtoflavone (25 microM)
      induction of CYP1A1 activities. In collagen gel sandwich cultures, hepatocytes
      remained arrested in mid-G1 phase of the cell cycle, even in the presence of EGF.
      In conventional primary cultures, caspases 8 and 3 were activated at 3 and 5 days
      after plating respectively. In collagen gel sandwich cultures, we found that
      neither collagen I nor EGF prevented activation of caspase 8 while collagen I gel
      inhibited activation of caspase 3, preventing spontaneous apoptosis of cultured
      rat hepatocytes. In contrast, EGF transiently increased caspase 3 activity at day
      1 after plating. Altogether, our data demonstrate that collagen I gel triggers
      intracellular signals which strongly affect cultured hepatocyte phenotype,
      leading to a cell cycle arrest in G1 phase and long-term survival through the
      inhibition of caspase 3 activation and that EGF-free medium improves survival and
      liver-specific gene expression in hepatocytes maintained in collagen I gel
      sandwich cultures.

PMID- 11322934
TI  - Role of nitric oxide on the increased vascular permeability and neutrophil
      accumulation induced by staphylococcal enterotoxin B into the mouse paw.
AB  - The role of nitric oxide (NO) on the increase in vascular permeability and
      neutrophil migration induced by staphylococcal enterotoxin B (SEB; 25
      microgram/paw) in the mouse was investigated in this study. The NO synthase
      inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) [but not its inactive
      enantiomer N(omega)-nitro-D-arginine methyl ester (D-NAME)], given intravenously
      (25-100 micromol/kg) or subplantarly (0.25-1.0 micromol/paw), reduced SEB-induced
      paw oedema significantly. A similar response was observed with aminoguanidine,
      given either intravenously (200-600 micromol/kg) or subplantarly (2
      micromol/paw). In contrast to paw oedema, the plasma exudation in response to SEB
      was not affected by the subplantar injection of L-NAME or aminoguanidine. The
      inhibition of oedema and plasma exudation by systemic treatment with L-NAME or
      aminoguanidine was reversed by co-injection of the vasodilator iloprost (0.3
      nmol/paw). Subplantar injection of SEB (25 microgram/paw) increased by 69% the
      myeloperoxidase (MPO) activity of SEB-treated paws, indicating the presence of
      neutrophils. Intravenous (12.5-50 micromol/kg) or subplantar (0.125-0.5
      micromol/paw) administration of L-NAME (but not of its inactive enantiomer, D
      NAME) largely reduced the MPO activity in SEB-treated paws. Similarly,
      intravenous (200-600 micromol/kg) or subplantar (2 micromol/paw) administration
      of aminoguanidine significantly reduced the MPO values of the SEB-injected paws.
      The vasodilator iloprost (0.3 nmol/paw) completely reversed the inhibition by L
      NAME or aminoguanidine of the MPO activity in SEB-injected paws. Our results show
      that the increased vascular permeability and neutrophil accumulation in response
      to subplantar injection of SEB in the mouse are inhibited by L-NAME and
      aminoguanidine by mechanisms probably involving reduction of local microvascular
      blood flow.

PMID- 11322935
TI  - Inhibition of T-cell invasion across cultured fibroblast monolayers by
      phenothiazine-related calmodulin inhibitors: impairment of lymphocyte motility by
      trifluoperazine and chlorpromazine, and alteration of the monolayer by pimozide.
AB  - Phenothiazines inhibit the typical shape changes displayed by activated
      lymphocytes and thereby their migration through polycarbonate filters. The
      structure activity relationship of this effect is distinct from calmodulin
      inhibition. Our aim was to study this effect of phenothiazines on lymphocyte
      migration in an environment with living solid tissue cells. We assessed the
      effect of trifluoperazine and chlorpromazine (TFP and CP, two strong inhibitors
      of lymphocyte motility) and pimozide (PIM, a much weaker inhibitor of lymphocyte
      motility but a strong inhibitor of calmodulin) on invasion of human Molt-4 T
      cells across precultured fibroblast monolayers. As expected invasion was
      inhibited by TFP and CP in the micromolar range that also inhibited motility.
      Surprisingly, PIM inhibited monolayer invasion at least as efficiently as TFP and
      CP (from 2.25 microM on). Preincubation of the monolayers or the lymphoid cells
      show that PIM exerted this novel invasion inhibiting effect on the monolayer. TFP
      and CP had a much weaker effect on the monolayer. Since these three compounds
      inhibit calmodulin in the same order, it is likely that this effect on the
      monolayer was caused by inhibition of a calmodulin-dependent pathway. KN-62, a
      specific inhibitor of calmodulin-dependent protein kinase II acted on the
      monolayer like PIM, whereas ML-7, a specific inhibitor of myosin regulatory light
      chain kinase, inhibited lymphoid cell motility like TFP and CP. In conclusion,
      invasion of T-cells across cellular monolayers is inhibited both by PIM and by
      phenothiazines like TFP and CP, but via distinct mechanisms: TFP and CP inhibit
      lymphocyte motility via a calmodulin independent pathway, whereas PIM impairs the
      monolayer's tolerance for invasion, most likely via a calmodulin and CamKII
      dependent pathway.

PMID- 11322936
TI  - The anti-inflammatory interactions of epinephrine with human neutrophils in vitro
      are achieved by cyclic AMP-mediated accelerated resequestration of cytosolic
      calcium.
AB  - This study was designed to evaluate the effects of epinephrine (0.01-1 microM) on
      superoxide production by, and release of elastase from human neutrophils
      activated with the chemotactic tripeptide, N-formyl-L-methionyl-L-leucyl-L
      phenylalanine (FMLP) (1 microM) in vitro, and to relate alterations in these
      responses to changes in adenosine 3,5' cyclic monophosphate (cAMP) and cytosolic
      free Ca(2+). Cyclic AMP, superoxide production and elastase release were measured
      by radioimmunoassay, lucigenin-enhanced chemiluminescence, and a colorimetric
      procedure respectively. Cytosolic Ca(2+) fluxes were measured by fura-2
      spectrofluorimetry in combination with radiometric procedures that enable
      distinction between net efflux and influx of the cation. Epinephrine treatment of
      neutrophils resulted in increased cAMP and dose-related inhibition of both
      superoxide production and elastase release, which was potentiated by the type 4
      phosphodiesterase inhibitor, rolipram, and attenuated by propranolol, but not by
      selective beta(1)-, alpha(1)- or alpha(2)-adrenoreceptor antagonists. Although
      epinephrine did not affect the FMLP-activated abruptly-occurring increase in fura
      2 fluorescence intensity, indicating no effects on the release of Ca(2+) from
      neutrophil intracellular stores, this agent accelerated the rate of decline in
      fluorescence in the setting of decreased efflux and a reduction in store-operated
      influx of Ca(2+). These effects of epinephrine on the clearance of Ca(2+) from
      the cytosol of FMLP-activated neutrophils were attenuated by propranolol, and are
      compatible with enhancement of the activity of the cAMP-dependent Ca(2+)
      sequestering/resequestering endo-membrane Ca(2+)-ATPase. We conclude that
      epinephrine down-regulates the pro-inflammatory activities of neutrophils by cAMP
      mediated enhancement of the clearance of cytosolic Ca(2+).

PMID- 11322937
TI  - Receptor accessory folding helper enzymes: the functional role of peptidyl prolyl
      cis/trans isomerases.
AB  - Receptor accessory peptidyl prolyl cis/trans isomerases (PPIases) of the FKBP and
      cyclophilin types form receptor heterocomplexes with different stabilities.
      PPIases have been found to associate with other receptor heterocomplex
      constituents via either proline-directed active sites or additional domains of
      the enzymes. The single-domain PPIases FKBP12 and FKBP12.6 are shown to interact
      with receptor protein kinases and calcium channels at their active sites. In
      contrast, heterooligomeric nuclear receptors contain multi-domain PPIases like
      FKBP51, FKBP52 or cyclophilin 40 that directly interact with the chaperone hsp90
      via the tetratricopeptide repeat modules of the folding helper enzymes. PPIases
      play a critical role in the functional arrangement of components within receptor
      heterocomplexes.

PMID- 11322938
TI  - Structural enzymology of biotin biosynthesis.
AB  - Over the last years, significant progress has been made in the understanding of
      the genetics and enzymology of the biosynthetic pathway of the vitamin biotin.
      The enzymes catalyzing the last four steps of this pathway, from pimeloyl-CoA to
      biotin, provide an ensemble of intriguing reaction mechanisms, which are
      presently being unravelled. The three-dimensional structures for three of these
      enzymes are known and provide a framework to which on-going mechanistic studies
      can be related.

PMID- 11322939
TI  - Mitochondrial permeability transition and oxidative stress.
AB  - Mitochondrial permeability transition (MPT) is a non-selective inner membrane
      permeabilization that may precede necrotic and apoptotic cell death. Although
      this process has a specific inhibitor, cyclosporin A, little is known about the
      nature of the proteinaceous pore that results in MPT. Here, we review data
      indicating that MPT is not a consequence of the opening of a pre-formed pore, but
      the consequence of oxidative damage to pre-existing membrane proteins.

PMID- 11322940
TI  - Gene therapy for streptozotocin-induced diabetic mice by electroporational
      transfer of naked human insulin precursor DNA into skeletal muscle in vivo.
AB  - Transfer of naked plasmid with insulin precursor DNA into skeletal muscle of
      streptozotocin (STZ)-induced diabetic mice through electroporation and detection
      of gene expression is described. Four different human insulin precursor DNA
      fragments were inserted into pcDNA3.1(-), downstream of a CMV promoter. Three of
      them, with a secretion signal sequence, succeeded in lowering blood glucose at a
      range of 30-50% in STZ diabetic mice. The other, with a synthetic DNA fragment
      encoding human proinsulin, failed. The mortality rate of very seriously STZ
      diabetic mice was reduced significantly by the treatment. The circulating insulin
      like protein (mouse insulin, human proinsulin, or intermediates during conversion
      of proinsulin to insulin) level in the blood of less seriously STZ diabetic mice
      treated with the human preproinsulin gene with an intron was about 15-23
      microU/ml, while that of STZ diabetic mice treated with empty vector was only
      about 6 microU/ml and that of normal mice was about 18 microU/ml. Transcription
      of the three human insulin precursor DNAs in mouse skeletal muscle was also
      detected by RT-PCR. The human preproinsulin gene with the intron showed a
      slightly higher potency in reducing blood glucose of mildly diabetic mice. These
      studies indicate that the skeletal muscle transferred with appropriate
      preproinsulin DNA by electroporation in vivo can secrete insulin-like protein
      resulting in reduction of blood glucose, and a basal blood insulin level can be
      achieved for at least 1 month.

PMID- 11322941
TI  - Rab4 affects both recycling and degradative endosomal trafficking.
AB  - The small GTPases Rab4, Rab5 and Rab7 are endosomal proteins which play important
      roles in the regulation of various stages of endosomal trafficking. Rab4 and Rab5
      have both been localized to early endosomes and have been shown to control
      recycling and endosomal fusion, respectively. Rab7, a marker of the late
      endosomal compartment, is involved in the regulation of the late endocytic
      pathway. Here, we compare the role of Rab4, Rab5 and Rab7 in early and late
      endosomal trafficking in HeLa cells monitoring ligand uptake, recycling and
      degradation. Expression of the Rab4 dominant negative mutant (Rab4AS22N) leads to
      a significant reduction in both recycling and degradation while, as expected,
      Rab7 mutants exclusively affect epidermal growth factor (EGF) and low density
      lipoprotein degradation. As also expected, expression of the dominant negative
      Rab5 mutant perturbs internalization kinetics and affects both recycling and
      degradation. Expression of Rab4WT and dominant positive mutant (Rab4AQ67L)
      changes dramatically the morphology of the transferrin compartment leading to the
      formation of membrane tubules. These transferrin positive tubules display
      swellings (varicosities) some of which are positive for early endosomal antigen-1
      and contain EGF. We propose that the Rab4GTPase is important for the function of
      the early sorting endosomal compartment, affecting trafficking along both
      recycling and degradative pathways.

PMID- 11322942
TI  - Overexpressed human survival motor neurone isoforms, SMNDeltaexon7 and SMN+exon7,
      both form intranuclear gems but differ in cytoplasmic distribution.
AB  - Homozygous mutations of the telomeric survival motor neurone gene (SMN1) cause
      spinal muscular atrophy (SMA). The centromeric copy gene (SMN2) generally skips
      exon 7 during splicing and fails to compensate for SMN1 deficits, so SMA cells
      have reduced SMN protein and few nuclear gems. To investigate the role of exon 7
      in SMN localisation, cDNAs for full-length SMN and SMNDeltaexon 7 were
      overexpressed in COS cells, neurones and SMA fibroblasts. Both constructs formed
      discrete intranuclear bodies colocalising with p80-coilin, but produced more
      cytoplasmic aggregates in cells overexpressing exon 7. Hence, the exon 7 domain
      enhances SMN aggregation but is not critical for gem formation.

PMID- 11322943
TI  - Stereochemistry of family 52 glycosyl hydrolases: a beta-xylosidase from Bacillus
      stearothermophilus T-6 is a retaining enzyme.
AB  - A beta-xylosidase from Bacillus stearothermophilus T-6 assigned to the
      uncharacterized glycosyl hydrolase family 52 was cloned, overexpressed in
      Escherichia coli and purified. The enzyme showed maximum activity at 65 degrees C
      and pH 5.6-6.3. The stereochemistry of the hydrolysis of p-nitrophenyl beta-D
      xylopyranoside was followed by 1H-nuclear magnetic resonance. Time dependent
      spectrum analysis showed that the configuration of the anomeric carbon was
      retained, indicating that a retaining mechanism prevails in family 52 glycosyl
      hydrolases. Sequence alignment and site-directed mutagenesis enabled the
      identification of functionally important amino acid residues of which Glu337 and
      Glu413 are likely to be the two key catalytic residues involved in enzyme
      catalysis.

PMID- 11322944
TI  - Binding of tenascin-X to decorin.
AB  - Tenascin-X (TN-X) is an extracellular matrix protein whose absence results in an
      alteration of the mechanical properties of connective tissue. To understand the
      mechanisms of integration of TN-X in the extracellular matrix, overlay blot
      assays were performed on skin extracts. A 100 kDa molecule interacting with TN-X
      was identified by this method and this interaction was abolished when the extract
      was digested by chondroitinase. By solid-phase assays, we showed that dermatan
      sulfate chains of decorin bind to the heparin-binding site included within the
      fibronectin-type III domains 10 and 11 of TN-X. We thus postulate that the
      association of TN-X with collagen fibrils is mediated by decorin and contributes
      to the integrity of the extracellular network.

PMID- 11322945
TI  - Thermal stability of the hemagglutinin-neuraminidase from Sendai virus evidences
      two folding domains.
AB  - The domain structure of hemagglutinin-neuraminidase from Sendai virus (cHN) was
      investigated by studying the thermal stability in the 20-100 degrees C range.
      Differential scanning calorimetry evidences two conformational transitions. The
      first transition is apparently a reversible two-state process, with Tm 48.3
      degrees C, and is shifted to 50.1 degrees C in the presence of the substrate
      analogue 2,3-dehydro-2-deoxy-N-acetyl neuraminic acid, meaning that the substrate
      binding domain is involved in the transition. The second transition, with
      apparent Tm 53.2 degrees C, is accompanied by irreversible loss of enzymatic
      activity of the protein, and the presence of the substrate analogue does not
      affect the Tm. The data indicate that cHN is composed of two independent folding
      domains, and that only one domain is involved in the binding of the substrate.
      Our results suggest that the paramyxovirus neuraminidases have the folding
      properties of a two-domain protein.

PMID- 11322946
TI  - Backbone dynamics of the channel-forming antibiotic zervamicin IIB studied by 15N
      NMR relaxation.
AB  - The backbone dynamics of the channel-forming peptide antibiotic zervamicin IIB
      (Zrv-IIB) in methanol were studied by 15N nuclear magnetic resonance relaxation
      measurements at 11.7, 14.1 and 18.8 T magnetic fields. The anisotropic overall
      rotation of the peptide was characterized based on 15N relaxation data and by
      hydrodynamic calculations. 'Model-free' analysis of the relaxation data showed
      that the peptide is fairly rigid on a sub-nanosecond time-scale. The residues
      from the polar side of Zrv-IIB helix are involved in micro-millisecond time-scale
      conformational exchange. The conformational exchange observed might indicate
      intramolecular processes or specific intermolecular interactions of potential
      relevance to Zrv-IIB ion channel formation.

PMID- 11322948
TI  - Electrophysiological characterization of BmK M1, an alpha-like toxin from Buthus
      martensi Karsch venom.
AB  - The present study investigates the electrophysiological actions of BmK M1, an
      alpha-like toxin purified from the venom of the scorpion Buthus martensi Karsch,
      on voltage-gated Na+ channels. Using the voltage clamp technique, we assessed the
      BmK M1 activity on the cardiac Na+ channel (hH1) functionally expressed in
      Xenopus oocytes. The main actions of the toxin are a concentration-dependent
      slowing of the inactivation process and a hyperpolarizing shift of the steady
      state inactivation. This work is the first electrophysiological characterization
      of BmK M1 on a cloned Na+ channel, demonstrating that this toxin belongs to the
      class of scorpion alpha-toxins. Our results also show that BmK M1 can be
      considered as a cardiotoxin.

PMID- 11322947
TI  - Two splicing variants of a new inhibitor of apoptosis gene with different
      biological properties and tissue distribution pattern.
AB  - Using homology searches, we identified a novel human inhibitor of apoptosis (IAP)
      gene. This gene has two splicing variants that contain open reading frames of 298
      and 280 amino acids and both contained a single copy of baculovirus IAP repeat
      (BIR) and RING domain. We refer here to the longer and shorter variants as Livin
      alpha and beta, respectively. Semiquantitative reverse transcriptase-polymerase
      chain reaction demonstrated a tissue-specific and non-correlated expression
      pattern in both adult and fetal tissues. Both mRNA variants were detected in
      various transformed cell lines. Despite their very close similarity, the two
      isoforms have different antiapoptotic properties. Both isoforms have a
      significant antiapoptotic activity in the Jurkat T cell line after triggering
      apoptosis via tumor necrosis factor and CD95 receptors. The Livin alpha but not
      beta protects cells from apoptosis induced by staurosporine, but in contrast,
      apoptosis initiated by etoposide was blocked only by the beta isoform. This
      difference in biological activities may indicate the presence of critical amino
      acids outside the BIR and RING domains. These functional and tissue distribution
      differences of Livin alpha and beta suggest that Livin may play a complex role in
      the regulation of apoptosis.

PMID- 11322949
TI  - IFNalpha sensitizes ME-180 human cervical cancer cells to TNFalpha-induced
      apoptosis by inhibiting cytoprotective NF-kappaB activation.
AB  - Tumor necrosis factor alpha (TNFalpha) induces apoptosis of a variety of tumor
      cell types. The anti-tumor effect of TNFalpha is often augmented by interferon
      (IFN) gamma. We hypothesized that IFNalpha, which shares many biological
      activities with IFNgamma, might also synergize with TNFalpha for the induction of
      tumor cell death. We tested our hypothesis using ME-180 human cervical cancer
      cells exposed to either IFNalpha or TNFalpha alone or both. We analyzed the death
      of ME-180 cells by biochemical and cytological means, and investigated the
      molecular mechanism underlying cytotoxic synergism between the two cytokines. We
      found that (i) IFNalpha/TNFalpha synergistically induced apoptosis of ME-180
      cells, which was accompanied by activation of caspases-3 and -8; (ii) IFNalpha
      induced signal transducer and activator of transcription (STAT) 1
      phosphorylation, and transfection of phosphorylation-defective STAT1 dominant
      negative mutant inhibited IFNalpha/TNFalpha-induced apoptosis; (iii) inhibition
      of nuclear factor kappaB (NF-kappaB) by proteasome inhibitor MG-132 sensitized ME
      180 cells to TNFalpha alone; (iv) IFNalpha treatment attenuated TNFalpha-induced
      NF-kappaB reporter activity, while it did not inhibit DNA binding of NF-kappaB.
      Taken collectively, our results indicate that IFNalpha sensitizes ME-180 cells to
      TNFalpha-induced apoptosis by inhibiting TNFalpha-mediated cytoprotective NF
      kappaB activation, and this sensitizing effect of IFNalpha is mediated through a
      STAT1-dependent pathway.

PMID- 11322950
TI  - Ser727-dependent transcriptional activation by association of p300 with STAT3
      upon IL-6 stimulation.
AB  - Activation of the signal transducer and activator of transcription 3 (STAT3) in
      response to interleukin-6 (IL-6) type cytokines involves both phosphorylation of
      Tyr705, which enables dimerization, nuclear translocation and DNA binding, as
      well as ser727 phosphorylation. Here, we describe that the 65 C-terminal amino
      acids of STAT3 can function as an independent transcription activation domain
      (TAD), particularly when a negative charge is introduced at position 727 by
      mutation of the serine residue into aspartate. The strong transcriptional
      activity of the C-terminal STAT3 Ser727Asp TAD is coupled to a constitutive
      association with the co-activator p300. In HepG2 cells, p300 associates with
      STAT3 upon IL-6 stimulation, and overexpression of p300 enhances the
      transcriptional activity of STAT3alpha, but not of STAT3beta or STAT3 Ser727Ala.
      We conclude that Ser727 phosphorylation in the C-terminal region of STAT3 is
      required for transactivation by association with p300.

PMID- 11322951
TI  - Analysis of the spatial, temporal and tissue-specific transcription of gamma
      sarcoglycan gene using a transgenic mouse.
AB  - To evaluate the promoter function of the 5'-flanking sequence of mouse gamma
      sarcoglycan (gamma-SG) gene in vivo, we generated transgenic mice harboring this
      sequence fused with enhanced green fluorescent protein reporter gene. The
      reporter expression was restricted in striated muscles and particularly strong in
      all myofibers in skeletal muscles. Using these mice, we examine the spatial and
      temporal transcriptional patterns of the gamma-SG gene during mouse skeletal
      muscle development. The expression of basic helix loop helix transcriptional
      factors preceded that of the reporter. Differences between the expression of
      reporter and endogenous gamma-SG genes in non-muscle tissues suggested the
      existence of additional promoter elements in the endogenous gene, and the
      analysis of endogenous mRNAs demonstrated the existence of a novel upstream exon
      and promoter active in non-muscle tissues.

PMID- 11322952
TI  - The G protein beta3 subunit 825T allele is a genetic marker for enhanced T cell
      response.
AB  - The G protein beta3 subunit (GNB3) 825T allele is predictive of enhanced Gi
      protein activation. Studying the influence of C825T allele status on cellular in
      vitro immune responses towards recall antigens and interleukin-2 stimulation we
      observed a 2-4-fold, significantly increased proliferation in homozygous 825T
      (TT) vs. C825 allele (CC) carriers. Furthermore, lymphocyte chemotaxis and CD4(+)
      T cell counts of individuals with TT+TC genotypes were significantly enhanced
      compared to the CC genotype. In summary, it appears that C825T allele status is
      highly predictive of immunocompetence and could be a candidate gene in disorders
      associated with inadequate immune response.

PMID- 11322953
TI  - Molecular characterization of human UDP-glucuronic acid/UDP-N-acetylgalactosamine
      transporter, a novel nucleotide sugar transporter with dual substrate
      specificity.
AB  - A novel human nucleotide sugar transporter (NST) which transports both UDP
      glucuronic acid (UDP-GlcA) and UDP-N-acetylgalactosamine (UDP-GalNAc) has been
      identified, cloned and characterized. The strategy for the identification of the
      novel NST involved a search of the expressed sequence tags database for genes
      related to the human UDP-galactose transporter-related isozyme 1, followed by
      heterologous expression of a candidate gene (hUGTrel7) in Saccharomyces
      cerevisiae and biochemical analyses. Significantly more UDP-GlcA and UDP-GalNAc
      were translocated from the reaction medium into the lumen of microsomes prepared
      from the hUGTrel7-expressing yeast cells than into the control microsomes from
      cells not expressing hUGTrel7. The possibility that this transporter participates
      in glucuronidation and/or chondroitin sulfate biosynthesis is discussed.

PMID- 11322954
TI  - Mechanisms for the transport of unconjugated bilirubin in human trophoblastic
      BeWo cells.
AB  - To evaluate mechanisms that mediate passage of unconjugated bilirubin (UCB)
      across placenta, the transport of [3H]UCB was studied in the human trophoblastic,
      BeWo cell line. When plotted against the unbound UCB concentration [Bf], uptake
      exhibited saturative kinetics with a similar apparent Km ( approximately 30 nM)
      for BeWo cells grown either in polarized (Transwell) or non-polarized fashion
      (dish). UCB release from cells, but not uptake, was inhibited by
      sulfobromophthalein but not by taurocholate, and almost abolished by MK571, a
      specific inhibitor of the activity of multidrug resistance-associated proteins
      (MRPs). MRP1 and MRP5 were both present in BeWo cells and the expression of MRP1,
      but not MRP5, was markedly higher in polarized cells. These data indicate that
      UCB is taken up from the fetal circulation by a still undefined, saturative
      process not shared by other organic anions and is then excreted to maternal
      circulation by proteins of the MRP family.

PMID- 11322955
TI  - Pharmacological properties of the mouse neurotensin receptor 3. Maintenance of
      cell surface receptor during internalization of neurotensin.
AB  - We recently reported the molecular identification of a new type of receptor for
      the neuropeptide neurotensin (NT), the neurotensin receptor 3 (NTR3), identical
      to sortilin, which binds receptor-associated protein. Here, we demonstrate that
      the cloned mouse NTR3 is expressed on the plasma membrane of transfected COS-7
      cells. The mouse NTR3 is detectable by photoaffinity labeling and immunoblotting
      at the cell surface as a 100 kDa N-glycosylated protein. Biochemical analysis and
      confocal microscopic imaging clearly indicate that NT is efficiently internalized
      after binding to NTR3, and that despite this internalization, the amount of
      receptor present on the cell surface is maintained.

PMID- 11322956
TI  - Functional role of the HIV-1 Rev exon 1 encoded region in complex formation and
      trans-dominant inhibition.
AB  - To study functional aspects of the exon 1 encoded region of the human
      immunodeficiency virus type 1 Rev protein, the viral Tev protein which exhibits
      low Rev activity but lacks the rev exon 1 encoded region was examined. Neither
      Rev-Tev heteromer complex formation nor inhibition of Rev by an export deficient
      Tev mutant was observed. Insertion of the rev exon 1 encoded region into the Tev
      mutant allowed it to oligomerize with Rev and act as a trans-dominant negative
      mutant. This showed that the exon 1 encoded region of Rev is essential for
      oligomerization and that oligomerization is a prerequisite for trans-dominant
      inhibition.

PMID- 11322957
TI  - Duffy-null promoter heterozygosity reduces DARC expression and abrogates adhesion
      of the P. vivax ligand required for blood-stage infection.
AB  - The Duffy blood group antigen is an essential receptor for Plasmodium vivax entry
      into erythrocytes in a process mediated by the parasite ligand, the Duffy binding
      protein (DBP). Recently, individuals living in a malaria endemic region of Papua
      New Guinea were identified as heterozygous for a new allele conferring Duffy
      negativity, which results in 50% less Duffy antigen on their erythrocytes. We
      demonstrate that DBP adherence to erythrocytes is significantly reduced for
      erythrocytes from heterozygous individuals who carry one Duffy antigen negativity
      allele. These data provide evidence that emergence of this new allelic form of
      Duffy negativity is correlated with resistance against vivax malaria.

PMID- 11322958
TI  - Glutamic acid 160 is the acid-base catalyst of beta-xylosidase from Bacillus
      stearothermophilus T-6: a family 39 glycoside hydrolase.
AB  - A beta-xylosidase from Bacillus stearothermophilus T-6 was cloned, overexpressed
      in Escherichia coli and purified to homogeneity. Based on sequence alignment, the
      enzyme belongs to family 39 glycoside hydrolases, which itself forms part of the
      wider GH-A clan. The conserved Glu160 was proposed as the acid-base catalyst. An
      E160A mutant was constructed and subjected to steady state and pre-steady state
      kinetic analysis together with azide rescue and pH activity profiles. The
      observed results support the assignment of Glu160 as the acid-base catalytic
      residue.

PMID- 11322959
TI  - The human and murine protocadherin-beta one-exon gene families show high
      evolutionary conservation, despite the difference in gene number.
AB  - Extensive cDNA analysis demonstrated that all human and mouse protocadherin-beta
      genes are one-exon genes. The protein sequences of these genes are highly
      conserved, especially the three most membrane-proximal extracellular domains.
      Phylogenetic analysis suggested that this unique gene family evolved by
      duplication of one single protocadherin-beta gene to 15 copies. The final
      difference in the number of protocadherin-beta genes in man (#19) and mouse (#22)
      is probably caused by duplications later in evolution. The complex relationship
      between human and mouse genes and the lack of pseudogenes in the mouse
      protocadherin-beta gene cluster suggest a species-specific evolutionary pressure
      for maintenance of numerous protocadherin-beta genes.

PMID- 11322960
TI  - Increase in the molecular weight and radius of gyration of apocalmodulin induced
      by binding of target peptide: evidence for complex formation.
AB  - Small-angle X-ray scattering was used to investigate a complex state of
      apocalmodulin induced by the binding of a Ca(2+)/calmodulin-dependent protein
      kinase IV calmodulin target site. Upon binding of the peptide, the molecular
      weight for apocalmodulin increased by 8.4%, which provides direct evidence for
      the formation of a calmodulin/target peptide complex. Comparison of the radius of
      gyration and Kratky plots of the apocalmodulin/peptide complex with those of
      apocalmodulin indicates that the overall conformation remains unchanged but the
      flexibility of the central linker decreases. An analysis of residue pairs between
      calmodulin and the target peptides suggests that the complex formation is induced
      by electrostatic interactions and subsequent van der Waals interactions.

PMID- 11322961
TI  - Curcumin induces the mitochondrial permeability transition pore mediated by
      membrane protein thiol oxidation.
AB  - Curcumin is a natural compound showing antiproliferative properties. Recent
      studies suggest that these properties might be due to its ability to induce
      apoptosis in tumor cells. As mitochondria play a pivotal role in the induction of
      the apoptotic process, we analyzed the effect of curcumin on mitochondrial
      function. Curcumin induced an increase in rat liver mitochondrial membrane
      permeability, resulting in swelling, loss of membrane potential and inhibition of
      ATP synthesis. These effects were mediated by the opening of the permeability
      transition pore. Curcumin pore induction involved the oxidation of membrane thiol
      functions and required the presence of low Ca(2+) concentrations. These data
      suggest that mitochondria might be a target by which curcumin induces apoptosis
      of tumor cells.

PMID- 11322962
TI  - Polyclonal antibodies to EB1089 (seocalcitol), an analog of 1alpha,25
      dihydroxyvitamin D(3)*.
AB  - A hapten derivative of EB1089 [1(R),3(S),25-trihydroxy-26,27-dimethyl-9,10-seco
      24-homocholesta-5(Z),7(E),10(19),22(E),24(E)-pentaene], a side-chain analog of
      1alpha,25-dihydroxyvitamin D(3), was synthesized for raising antibodies with a
      high specificity for EB1089. The A-ring moiety of EB1089 was replaced in the
      hapten by a linker for conjugation to a protein. Three polyclonal antibodies were
      obtained by immunizing rabbits with a BSA-conjugate of the hapten. The antibodies
      were characterized for titer, avidity and specificity using an enzyme immunoassay
      with covalently bound EB1089. The three antibodies had similar binding profiles
      and were highly selective for EB1089 and its metabolites over the naturally
      occurring vitamin D metabolites. Cross-reactivities with 25-hydroxyvitamin D(3),
      the most abundant vitamin D metabolite in serum, were in the range 0.01-0.2%
      relative to EB1089.

PMID- 11322963
TI  - Preventing estrogen receptor action with dimer-interface peptides.
AB  - The human estrogen receptor-alpha (hER) is a ligand-activated transcription
      factor that functions as a homodimer. We sought to further understand the
      molecular processes involved in dimerization, and to develop a reagent that may
      function as an antiestrogen independent of the ligand binding site. To this end,
      we designed a 16-residue 'dimer-interface' oligopeptide derived from the helical
      region of the hER which is directly involved in dimerization. This peptide,
      termed the I-box peptide, has a high helical propensity in aqueous solution. The
      I-box peptide blocks hER action by causing aggregation and precipitation of both
      the ligand-bound and apo-hER. This effect is dependent on the helical nature of
      the peptide. A single Ile to Pro mutation in the helical region of the I-box
      peptide significantly reduces the helical content and abolishes the precipitation
      activity. Furthermore, the peptide activity appears to be specific for the hER.
      The I-box peptide does not significantly affect other proteins or steroid
      receptors tested. A homologous peptide derived from the nuclear receptor RXRalpha
      dimer interface, and a LXXLL-containing peptide from the coactivator TIF2 have no
      detectable in vitro effect on hER function or solubility. Our data suggest that
      rationally designed molecules capable of affecting steroid receptor quaternary
      structures may be potential avenues for the development of specific inhibitors of
      this class of proteins.

PMID- 11322964
TI  - Gonadotropins at menopause: the influence of obesity, insulin resistance, and
      estrogens.
AB  - Obese, postmenopausal women have lower FSH levels. To determine whether this is
      due to higher estrogen exposure, we compared feedback gonadotropin sensitivity
      and its relation to insulin resistance in four groups of obese and lean,
      postmenopausal women. Group one was treated with 400 mg troglitazone (TG) daily
      for two weeks; 150 clomiphene citrate (CC) was added daily for the second week.
      Group two received 150 mg CC daily for a week. Group three received 1000 mg
      metformin (MET) daily for two weeks, with 120 mg raloxifene (RAL) added during
      the second week. Group four received 120 mg RAL for a week. Before and after each
      period, a serum pool was obtained from samples taken every minute during a 10 ml
      interval. The women recruited for this study were categorized as obese or lean
      based on BMI >/= 29 or BMI < 29, respectively. Obese, menopausal women had lower
      FSH (45.5 IU/l) and LH (16.2 IU/l) values than those of lean (64.1 IU/l and 23.0
      IU/l), but the obese menopausal women had higher leptin, DHEAS, glucose, insulin,
      and HOMA-IR levels. Log [FSH] was associated with BMI (r = -0.53, P < 0.000001)
      and number of pregnancies (r = -0.37, P = 0.0009). TG treatment did not change
      HOMA-IR or gonadotropin levels, but DHEAS and androstenedione levels decreased
      significantly. CC alone or together with TG, diminished FSH (-7.9 and -9.2) and
      LH (-2.5 and -3.6) concentrations, with a greater reduction in lean women. MET
      reduced glucose and the HOMA-IR index without affecting gonadotropin or steroid
      levels. CONCLUSIONS: obese, menopausal women have lower FSH levels due to greater
      estrogen exposure, by mechanisms unrelated to insulin resistance.

PMID- 11322965
TI  - Synthesis of C-5'-alkyl substituted 17-spirofuran 19-norsteroids.
AB  - A number of new steroidal 17-spirofuran derivatives of the 19-nor series
      containing Me, Et or (i)Pr-substituents in the heterocyclic moiety has been
      prepared, which are expected to have a strong progestagenic activity. The
      proposed approach made use of the 1-3-dipolar cycloaddition of low-molecular
      nitrile oxides with steroidal acetylenic alcohols followed by transformation of
      the isoxazole side chain.

PMID- 11322966
TI  - Ergosteroids IV: synthesis and biological activity of steroid glucuronosides,
      ethers, and alkylcarbonates.
AB  - The 7-oxo derivative of dehydroepiandrosterone is more active than the parent
      steroid and is devoid of adverse side effects in rats, monkeys and humans. In
      anticipation of possible therapeutic use we have sought more active, longer
      lasting forms of 7-oxo- and 7beta-hydroxydehydroepiandrosterones. The 7-oxo- and
      7-hydroxy steroids have been converted to glucuronides, ethers and carbonate
      esters. The syntheses of these compounds are described and their ability to
      induce the formation of liver thermogenic enzymes when fed to rats is reported.
      Some of the new derivatives were found to be somewhat more effective than the
      equimolar amounts of 7-oxo-DHEA with which they were compared in each experiment.

PMID- 11322967
TI  - Correlation between different gene expression assays designed to measure trans
      activation potencies of systemic glucocorticoids.
AB  - The glucocorticoids (GC) betamethasone, dexamethasone, hydrocortisone,
      methylprednisolone, prednisolone and triamcinolone acetonide are currently used
      in the treatment of inflammatory diseases. Through a process called trans
      activation, GC activate gene expression and produce various physiological and
      pharmacological effects. In particular, by inducing gluconeogenic enzymes, long
      term GC treatment may cause diabetes. Using three different assays, we have
      extensively compared the capacity of the above GC to activate gene expression.
      trans-Activation of a GC inducible luciferase gene was assessed in HeLa and A549
      cells after stable and transient transfection, respectively. In hepatoma tissue
      culture cells, we measured trans-activation of the endogenous gene encoding
      tyrosine aminotransferase, a gluconeogenic enzyme. Half-maximal effective
      concentrations of GC were determined by dose-response analyses. Results obtained
      with these assays were highly correlated and GC were ranked in three groups
      according to their trans-activation potency: betamethasone, dexamethasone, and
      triamcinolone acetonide > methylprednisolone and prednisolone > hydrocortisone.
      Potencies were not strictly related to receptor binding affinities and not
      significantly affected by the amount of endogenous GC receptor.

PMID- 11322969
TI  - Imaging visual function with the multifocal m-sequence technique.
AB  - The multifocal m-sequence technique is a versatile set of tools for visual
      electrophysiology designed to provide access to the complex dynamic interplay of
      converging signals in the central nervous system. Here, a number of uses for the
      technique are demonstrated, with examples from human electroretinography. A
      simple relationship between the binary kernels extracted from a single experiment
      permits us to distinguish local from lateral interactions in the retina.
      Transformation of the series of binary kernels into response sequences provides
      new insight into unexpected fast dynamic properties of retinal responses and
      facilitates future modeling of the signals as well as identification of the
      signal sources.

PMID- 11322970
TI  - Functional brain imaging based on ERD/ERS.
AB  - Sensory, cognitive and motor processing can result in changes of the ongoing EEG
      in form of an event-related desynchronization (ERD) or event-related
      synchronization (ERS). Both phenomena are time-locked but not phase-locked to the
      event and they are highly frequency-band specific. The ERD is interpreted as a
      correlate of an activated cortical area with increased excitability and the ERS
      in the alpha and lower beta bands can be interpreted, at least under certain
      circumstances, as a correlate of a deactivated cortical area. Spatial mapping of
      ERD/ERS can be used to study the dynamics of cortical activation patterns.
      Examples from a movement task are reported.

PMID- 11322971
TI  - High-resolution spatio-temporal mapping of visual pathways using multi-electrode
      arrays.
AB  - The parallel processing of visual information was studied with penetrating
      microelectrode arrays. We studied the high-resolution visuotopic organization of
      cat primary visual cortex, and the encoding of simple visual stimuli by ensembles
      of ganglion cells in the isolated turtle retina. The high-resolution visuotopic
      organization of visual cortex is non-conformal. Regions of visual cortex
      separated by 400 mu may have receptive field centers that are separated by as
      much as 3 degrees, or they may superimpose. Ganglion cells are 'generalists', and
      are poor specifiers of the color of full field visual stimuli. Groups of
      'luminosity' type ganglion cells can assist in the specification of stimulus
      color, but even individual 'chromatic' ganglion cells are not capable of quality
      color specification. These basic studies have relevance to the development of
      visual neuroprostheses based upon electrical stimulation of the retina and
      cortex.

PMID- 11322972
TI  - PET/SPECT: functional imaging beyond flow.
AB  - In this review, first principles of positron emission tomography (PET) and single
      photon emission tomography (SPECT) are discussed together with the relative
      strengths and weaknesses of both techniques. With both modalities it is possible
      to image and, especially with PET, to measure regional tissue function, the
      particular function being interrogated depending on the actual tracer being used.
      In the second part, the use of PET for neuroactivation studies is presented,
      illustrated with some key examples from the literature using both perfusion and
      metabolism tracers. It is argued that the future of PET (and SPECT)
      neuroactivation studies lies in the use of ligands. Possible approaches for
      performing ligand activation studies are discussed.

PMID- 11322973
TI  - Measurement of corneal sublayer thickness and transparency in transgenic mice
      with altered corneal clarity using in vivo confocal microscopy.
AB  - Measurement of sublayer thickness and transparency at cellular level in the
      living animal are critical to understanding the role of specific transgenes and
      transgene products in controlling corneal development and maintenance of
      transparency. Using two different transgenic mouse strains having altered corneal
      clarity, we have evaluated the ability of in vivo confocal microscopy to measure
      corneal haze and localize light scattering structures. Projection of 2-D and 3-D
      image information identified the nature and location of light scattering within
      the cornea and allowed correlation of unique structural differences to transgene
      expression. Our findings suggest that in vivo confocal microscopy can be used to
      identify the effects of transgene expression on mouse corneal transparency.

PMID- 11322974
TI  - Packing arrangement of the three cone classes in primate retina.
AB  - We describe a detailed analysis of the spatial arrangement of L, M and S cones in
      the living eyes of two humans and one monkey. We analyze the cone mosaics near 1
      degrees eccentricity using statistical methods that characterize the arrangement
      of each type of cone in the mosaic of photoreceptors. In all eyes, the M and L
      cones are arranged randomly. This gives rise to patches containing cones of a
      single type. In human, but not in monkey, the arrangement of S-cones cannot be
      distinguished from random.

PMID- 11322975
TI  - MR studies of retinal oxygenation.
AB  - In this paper, we summarize the development and application of two novel magnetic
      resonance based measurements of retinal oxygenation in experimental models of
      retinopathy, including diabetic retinopathy and retinopathy of prematurity. We
      use 19F-NMR and a small (microl) perfluorocarbon drop positioned in the
      preretinal vitreous space to make PO2 measurement of the inner retina. In
      addition, we use magnetic resonance imaging (MRI) to accurately and non
      invasively measure the change in the preretinal PO2 (DeltaPO2) following the
      shift from breathing room air to a hyperoxic inhalation challenge. The advantages
      and disadvantages of each method are discussed. New applications of these
      techniques in the newborn rat and adult mouse are presented. We expect such
      studies to motivate future MRI oxygenation studies of human retinopathy,
      including diabetic retinopathy and retinopathy of prematurity.

PMID- 11322976
TI  - Resolution, separation of retinal ganglion cells, and cortical magnification in
      humans.
AB  - We present direct comparisons of resolution thresholds and quantitative estimates
      of retinal ganglion cell separation in humans with reported functional magnetic
      resonance imaging estimates of the human linear cortical magnification factor.
      Measurements of resolution thresholds (MAR), retinal ganglion cell (GC)
      densities, and linear cortical magnification factor (M) values were taken from
      the literature. Our objective was to analyse the apparent overrepresentation of
      human central vision in the visual cortex and to determine whether the cause of
      this is an effect of the uneven distribution of GC in the retina and/or that
      central GC have more devoted cortical area per cell. The reserved amount of
      cortical distance per retinal unit, i.e. the product of M on the one hand and
      effective GC separation, MAR, and GC receptive field separation on the other,
      indicates an overrepresentation of the fovea and immediately surrounding retina
      in the human striate cortex due to an increase in devoted cortical distance per
      central GC or resolution unit. This cannot be explained by lateral displacement
      of foveal ganglion cells nor by peripheral scaling, but rather by an additional
      magnification in the retino-cortical pathway.

PMID- 11322977
TI  - Visual areas and spatial summation in human visual cortex.
AB  - Functional MRI measurements can securely partition the human posterior occipital
      lobe into retinotopically organized visual areas (V1, V2 and V3) with experiments
      that last only 30 min. Methods for identifying functional areas in the dorsal and
      ventral aspect of the human occipital cortex, however, have not achieved this
      level of precision; in fact, different laboratories have produced inconsistent
      reports concerning the visual areas in dorsal and ventral occipital lobe. We
      report four findings concerning the visual representation in dorsal regions of
      occipital cortex. First, cortex near area V3A contains a central field
      representation that is distinct from the foveal representation at the confluence
      of areas V1, V2 and V3. Second, adjacent to V3A there is a second visual area,
      V3B, which represents both the upper and lower quadrants. The central
      representation in V3B appears to merge with that of V3A, much as the central
      representations of V1/2/3 come together on the lateral margin of the posterior
      pole. Third, there is yet another dorsal representation of the central visual
      field. This representation falls in area V7, which includes a representation of
      both the upper and lower quadrants of the visual field. Fourth, based on visual
      field and spatial summation measurements, it appears that the receptive field
      properties of neurons in area V7 differ from those in areas V3A and V3B.

PMID- 11322978
TI  - A hierarchy of the functional organization for color, form and disparity in
      primate visual area V2.
AB  - By combining optical imaging, single unit electrophysiology and cytochrome
      oxidase (CO) histology, we sought to reveal in greater detail the functional
      organization within the CO stripes of visual area V2 of primates. To visualize
      the disparity selective regions of V2, the imaging of binocular interaction was
      employed. These imaging maps guided single unit penetrations that then revealed a
      columnar organization for disparity. Our studies also showed a pattern of
      intermixing between the color and disparity pathways of V2, including the
      existence of single cells tuned for both color and disparity. While previous
      studies have suggested that the CO stripes of V2 constitute the fundamental
      organizational unit within V2, our results show a further level of organization
      consisting of functionally distinct subcompartments, 0.7-1.5 mm in diameter,
      within individual stripes. These subcompartments, which are not clearly revealed
      by CO histochemistry, lie within each of the thin, pale, and thick CO dense
      stripes in V2 and are specific for aspects of color, orientation and retinal
      disparity, respectively. The present results favor an architectural view of V2,
      not unlike that of V1, as a collection of functionally distinct subcompartments
      or modules situated within each of the V2 stripes. These modules also support the
      notion that for each cortical area (e.g. V1, V2, V4), there exists a stereotyped
      cortical module with a geometry that is characteristic for each area. These
      modules exist as a middle tier in a hierarchy of functional organization within
      V2.

PMID- 11322979
TI  - Functional organisation of the saccadic reference system processing extraretinal
      signals in humans.
AB  - In order to investigate the neuronal network involved in processing extraretinal
      signals, functional magnetic resonance imaging (fMRI) was applied to subjects
      performing the double step saccade paradigm. There, the calculation of the
      amplitude of the second saccade must rely on extraretinal signals of the first.
      When compared to a task where both saccades could be performed by means of
      retinal signals alone, a parieto-frontal cortical network was activated,
      including lateral intraparietal area, precuneus, insula, inferior frontal gyrus
      and anterior cingulum.

PMID- 11322981
TI  - Event-related brain potentials during selective attention to depth and form in
      global stereopsis.
AB  - To elucidate the discriminating processes of surface depth and boundary form in
      global stereopsis, event-related brain potentials (ERPs) were investigated by the
      detection of combinations of the attributes in random sequences. The attentional
      relevance of depth or form was associated with selection negativities (SNs) over
      the lateral occipito-temporal regions initiating at about 200 ms post-stimulus.
      The initial SNs were elicited irrespective of relevance to the other feature; the
      following parts increased only for stimuli with crossed disparity having the
      relevant dimension of the other feature, suggesting the independent selection of
      stereoscopic depth and form followed by the perceptual integration into an
      object.

PMID- 11322980
TI  - Mapping visual cortex in monkeys and humans using surface-based atlases.
AB  - We have used surface-based atlases of the cerebral cortex to analyze the
      functional organization of visual cortex in humans and macaque monkeys. The
      macaque atlas contains multiple partitioning schemes for visual cortex, including
      a probabilistic atlas of visual areas derived from a recent architectonic study,
      plus summary schemes that reflect a combination of physiological and anatomical
      evidence. The human atlas includes a probabilistic map of eight topographically
      organized visual areas recently mapped using functional MRI. To facilitate
      comparisons between species, we used surface-based warping to bring functional
      and geographic landmarks on the macaque map into register with corresponding
      landmarks on the human map. The results suggest that extrastriate visual cortex
      outside the known topographically organized areas is dramatically expanded in
      human compared to macaque cortex, particularly in the parietal lobe.

PMID- 11322982
TI  - Building surfaces from borders in Areas 17 and 18 of the cat.
AB  - Several brightness illusions indicate that borders can dramatically affect the
      perception of adjoining surfaces. In the Craik-O'Brien-Cornsweet illusion, in
      particular, two equiluminant surfaces can appear different in brightness due to
      the contrast border between them. Although the psychophysical nature of this
      phenomenon has been well characterized, the neural circuitry underlying this
      effect is unexplored. Here, we have asked whether there are cells in visual
      cortex which respond to edge-induced illusory brightness percepts such as the
      Cornsweet. Using optical imaging and single unit recordings methods, we have
      studied responses of the primary (Area 17) and second (Area 18) visual cortical
      areas of the anesthetized cat to both real luminance change and Cornsweet
      brightness change. We find that there are indeed cells whose responses are
      modulated in phase with the modulation of the Cornsweet stimulus. These cells are
      present in both Area 17 and Area 18, but are more prevalent in Area 18. These
      responses are generally weak and are found even when receptive fields are distant
      from the contrast border. Consistent with perception, cells which respond to the
      Cornsweet border are modulated in antiphase to the Narrow Real (another border
      induced illusory brightness stimulus). Remarkably, we also find evidence of edge
      induced responses to illusory brightness change using intrinsic signal optical
      imaging. Both real luminance change and edge-induced brightness change produces a
      greater imaged response in Area 18 than in Area 17. Thus, in the absence of
      direct luminance stimulation, cells in visual cortex can respond to modulation of
      distant border contrasts. We suggest that the perception of surface brightness
      was encoded in the early visual cortical pathway by both surface luminance
      contrast signals in Area 17 (Rossi, A. F., Rittenhouse, C. D., & Paradiso, M. A.
      (1996). The representation of brightness in primary visual cortex. Science, 273,
      1104-7) and border-induced contrast signals that predominate in Area 18.

PMID- 11322983
TI  - The lateral occipital complex and its role in object recognition.
AB  - Here we review recent findings that reveal the functional properties of extra
      striate regions in the human visual cortex that are involved in the
      representation and perception of objects. We characterize both the invariant and
      non-invariant properties of these regions and we discuss the correlation between
      activation of these regions and recognition. Overall, these results indicate that
      the lateral occipital complex plays an important role in human object
      recognition.

PMID- 11322984
TI  - Integrating electrophysiology and neuroimaging of spatial selective attention to
      simple isolated visual stimuli.
AB  - Visual-spatial attention involves modulations of activity in human visual cortex
      as indexed by electrophysiological and functional neuroimaging measures. Prior
      studies investigating the time course and functional anatomy of spatial attention
      mechanisms in visual cortex have used higher-order discrimination tasks with
      complex stimuli (e.g. symbol matching in bilateral stimulus arrays, or letter
      discrimination), or simple detection tasks but in the presence of complex
      distracting information (e.g. luminance detection with superimposed symbols as
      distractors). Here we tested the hypothesis that short-latency modulations of
      incoming sensory signals in extrastriate visual cortex reflect an early spatially
      specific attentional mechanism. We sought evidence of attentional modulations of
      sensory input processing for simple, isolated stimuli requiring only an
      elementary discrimination (i.e. size discrimination). As in prior studies using
      complex symbols, we observed attention-related changes in regional cerebral blood
      flow in extrastriate visual cortex that were associated with changes in event
      related potentials at a specific latency range. These findings support the idea
      that early in cortical processing, spatially-specific attentional selection
      mechanisms can modulate incoming sensory signals based on their spatial location
      and perhaps independently of higher-order stimulus form.

PMID- 11322985
TI  - Putting spatial attention on the map: timing and localization of stimulus
      selection processes in striate and extrastriate visual areas.
AB  - This study investigated the cortical mechanisms of visual-spatial attention in a
      task where subjects discriminated patterned targets in one visual field at a
      time. Functional magnetic imaging (fMRI) was used to localize attention-related
      changes in neural activity within specific retinotopic visual areas, while
      recordings of event-related brain potentials (ERPs) traced the time course of
      these changes. The earliest ERP components enhanced by attention occurred in the
      time range 70-130 ms post-stimulus onset, and their neural generators were
      estimated to lie in the dorsal and ventral extrastriate visual cortex. The
      anatomical areas activated by attention corresponded closely to those showing
      increased neural activity during passive visual stimulation. Enhanced neural
      activity was also observed in the primary visual cortex (area V1) with fMRI, but
      ERP recordings indicated that the initial sensory response at 50-90 ms that was
      localized to V1 was not modulated by attention. Modeling of ERP sources over an
      extended time range showed that attended stimuli elicited a long-latency (160-260
      ms) negativity that was attributed to the dipolar source in area V1. This finding
      is in line with hypotheses that V1 activity may be modulated by delayed,
      reentrant feedback from higher visual areas.

PMID- 11322986
TI  - Sustained extrastriate cortical activation without visual awareness revealed by
      fMRI studies of hemianopic patients.
AB  - Patients with lesions in the primary visual cortex (V1) may show processing of
      visual stimuli presented in their field of cortical blindness even when they
      report being unaware of the stimuli. To elucidate the neuroanatomical basis of
      their residual visual functions, we used functional magnetic resonance imaging in
      two hemianopic patients, FS and GY. In the first experiment, a rotating spiral
      stimulus was used to assess the responsiveness of dorsal stream areas. Although
      no response was detectable within denervated or destroyed early visual cortex,
      motion-sensitive areas (hMT+/V5) ipsilateral to the lesion showed a strong
      sustained hemodynamic response. In GY, this activation was at least as strong as
      that of his contralesional hMT+/V5 to the stimulus in the normal hemifield. In
      the second experiment, coloured images of natural objects were used to assess the
      responsiveness of ventral stream areas. Again, no activity was detectable in
      ipsilesional early visual areas, but extrastriate areas in the lateral occipital
      cortex (hMT+/V5 and LO) and within the posterior fusiform gyrus (V4/V8) showed a
      robust sustained hemodynamic response. In both experiments, we observed that
      ipsilesional areas responded to stimuli presented in either hemifield, whereas
      the normal hemisphere responded preferentially to stimuli in the sighted
      hemifield. As only one subject occasionally noticed the onset of stimulation in
      the impaired field, the unexpectedly strong sustained activity in ipsilesional
      dorsal and ventral cortical areas appears to be insufficient to generate
      conscious vision.

PMID- 11322987
TI  - Brain activity evoked by inverted and imagined biological motion.
AB  - Previous imaging research has identified an area on the human posterior superior
      temporal sulcus (STS) activated upon viewing biological motion. The current
      experiments explore the relationship between neural activity within this region
      and perceptual experience. Biological motion perception is orientation dependent:
      inverting point-light animations make them more difficult to see. We measured
      activity levels within this region as observers viewed inverted point-light
      animations. We also measured neural activity while observers imagined biological
      motion and compared it to that measured while observers viewed the animations. In
      both experiments we found that the BOLD response was modulated with perceptual
      experience. Viewing inverted biological motion activated posterior STS more than
      scrambled motion, but less than upright biological motion. Mental imagery of
      biological motion was also sufficient to activate this region in most of our
      observers, but the level of activity was weaker than during actual viewing of the
      motion animations.

PMID- 11322988
TI  - Why only time will tell.
AB  - The nematode Caenorhabditis elegans has become a model system for the study of
      the genetic basis of aging. In particular, many mutations that extend life span
      have been identified in this organism. When loss-of-function mutations in a gene
      lead to life span extension, it is a necessary conclusion that the gene normally
      limits life span in the wild type. The effect of a given mutation depends on a
      number of environmental and genetic conditions. For example, the combination of
      two mutations can result in additive, synergistic, subtractive, or epistatic
      effects on life span. Valuable insight into the processes that determine life
      span can be obtained from such genetic analyses, especially when interpreted with
      caution, and when molecular information about the interacting genes is available.
      Thus, genetic and molecular analyses have implicated several genes classes (daf,
      clk and eat) in life span determination and have indicated that aging is affected
      by alteration of several biological processes, namely dormancy, physiological
      rates, food intake, and reproduction.

PMID- 11322989
TI  - Proteolysis, caloric restriction and aging.
AB  - The nature of the aging process has been the subject of considerable speculation.
      It is believed that free radical damage to cellular components is one of the main
      contributors to the aging process. Studies on proteins have shown age-related
      decline in enzyme activities, age-related accumulation of oxidized proteins and a
      decline of the proteolytic machinery of the cell. The proteasome, a highly
      regulated intracellular proteolytic system, is the major enzymatic system
      responsible for the degradation of damaged proteins. The current knowledge on
      regulation and of the properties of this unique proteolytic system with special
      emphasis to the aging process are discussed in this review. Since it is known
      that caloric restriction (CR) is the only method to delay the aging process and
      extend the maximal lifespan the effects of CR on the age-related decline in
      protein degradation is highlighted.

PMID- 11322990
TI  - Peroxidation of linoleic acid and its relation to aging and age dependent
      diseases.
AB  - Cell proliferation, cell injury and aging are connected with changes in the cell
      membrane structure. Apparently these changes activate, in mammalian as well as in
      plant cells, lipases which liberate polyunsaturated fatty acids (PUFAs). PUFAs
      are the substrates for lipoxygenases which convert them to corresponding
      hydroperoxides (LOOHs). Lipoxygenases commit suicide by releasing iron ions.
      LOOHs react with iron ions to generate radicals. Thus, a nonenzymic lipid
      peroxidation process (LPO) is induced. It is speculated that the change from
      enzymic to nonenzymic LPO is connected with the switch from apoptosis to necrosis
      and that LOOHs produced in enzymic reactions are degraded specifically to signal
      compounds which induce physiological responses, while nonenzymic reactions seem
      to induce generation of reactive oxygen species, cell death and age related
      diseases. Enzymic and nonenzymic LPO processes concern all PUFAs not only
      arachidonic acid. The main PUFA in mammals is linoleic acid. Since these products
      serve signalling functions, different degradation paths of linoleic
      hydroperoxides are described in detail and the physiological properties of LPO
      products are discussed in relation to aging and age related diseases.

PMID- 11322991
TI  - Emerging roles for telomerase in regulating cell differentiation and survival: a
      neuroscientist's perspective.
AB  - Telomerase is a reverse transcriptase that adds repeats of a DNA sequence
      (TTAGGG) to the ends of chromosomes (telomeres) in mitotic cells, thus
      maintaining their length and preventing cell cycle arrest and cell death
      (cellular senescence). During development of the nervous system, telomerase
      activity levels are high in neural progenitor cells, but then they decrease as
      cells differentiate or die. The catalytic subunit of telomerase (TERT) remains at
      relatively high levels during the process of neuronal differentiation and then
      decreases sharply during the period when synapses form and programmed cell death
      occurs. TERT promotes survival of developing brain neurons. Suppression of
      telomerase activity and TERT expression promotes apoptosis of neurons, whereas
      overexpression of TERT prevents apoptosis by suppressing cell death at a
      premitochondrial step in the death cascade TERT may suppress DNA damage and/or
      apoptotic signals activated by damaged DNA. Recent studies of the transcriptional
      regulation of the TERT gene suggest that this enzyme may mediate the cell
      survival-promoting actions of diverse signals including estrogen, cytokines and
      neurotrophic factors. The elucidation of the functions of telomerase activity and
      TERT in neuronal differentiation and survival may lead to novel approaches for
      preventing neuronal death and promoting recovery of function in various
      neurodegenerative conditions.

PMID- 11322992
TI  - Insulin-like signaling, metabolism, stress resistance and aging in Caenorhabditis
      elegans.
AB  - The nervous system acts as a major regulator of the life span of Caenorhabditis
      elegans. Temperature and chemical stimuli from the environment are integrated
      with internal signals from the reproductive system to specify adult longevity. An
      insulin-like signaling cascade acts in neurons and coordinates control of
      senescence of the entire organism by regulating metabolism and a stress response
      mechanism. Caloric restriction extends life span, possibly by activation of the
      stress response program.

PMID- 11322993
TI  - Telomere biology in human aging and aging syndromes.
AB  - Telomeres, the extreme ends of the chromosomes play a key role in the process of
      cellular aging. Due to the 'end-replication-problem', successive shortening of
      the telomeres with each cell division results in a mitotic clock and it was shown
      in vitro that this clock limits the replicative capacity of cell proliferation.
      Telomerase counteracts telomere erosion and provides some somatic cells an
      unlimited proliferative potential in vitro. The present views of telomeres and
      telomerase functions in cellular aging in vitro are presented. Possibilities and
      limitations in the evaluation of the in vivo impact of telomere erosion on human
      aging, aging syndromes and age related diseases are reviewed. Unresolved
      questions, future experimental approaches and emerging therapeutic applications
      are discussed.

PMID- 11322994
TI  - Stem cells and aging: expanding the possibilities.
AB  - In the very early stages of embryonic development, cells have the capability of
      dividing indefinately and then differentiating into any type of cell in the body.
      Recent studies have revealed that much of this remarkable developmental potential
      of embryonic stem cells is retained by small populations of cells within most
      tissues in the adult. Intercellular signals that control the proliferation,
      differentiation and survival of stem cells are being identified and include a
      diverse array of growth factors, cytokines and cell adhesion molecules.
      Intracellular mechanisms that regulate stem cell fate are also emerging and
      include established second messenger pathways, novel transcription factors and
      telomerase. The possibility that a decline in the numbers or plasticity of stem
      cell populations contributes to aging and age-related disease is suggested by
      recent findings. The remarkable plasticity of stem cells suggests that endogenous
      or transplanted stem cells can be 'tweaked' in ways that will allow them to
      replace lost or dysfunctional cell populations in diseases ranging from
      neurodegenerative and hematopoietic disorders to diabetes and cardiovascular
      disease.

PMID- 11322995
TI  - Molecular mechanisms of ageing in connective tissues.
AB  - The outward manifestations of tissue ageing occurring in the elderly primarily
      involve the two major structural proteins of the body, collagen and elastin. The
      changes in these proteins are associated with intermolecular cross-linking and
      side-chain modifications. Cross-linking involves two different mechanisms, a
      precise enzymic process during development and maturation, and a subsequent non
      enzymic adventitious reaction with glucose during ageing. The latter glycation
      reactions are the major cause of tissue dysfunction in the elderly due to cross
      linking, which stiffens the tissues, and to side-chain modification, which alters
      normal cell-matrix interactions. Photoageing by UV involves two competing
      reactions, chain cleavage and cross-linking, the former predominating on long
      term exposure. The molecular mechanisms involved are gradually being unravelled
      and will lead to the development of inhibitors of these deleterious effects of
      ageing.

PMID- 11322996
TI  - Suppression of brain aging and neurodegenerative disorders by dietary restriction
      and environmental enrichment: molecular mechanisms.
AB  - Dietary restriction (reduced calorie intake with nutritional maintenance) can
      extend lifespan and may increase the resistance of the nervous system to age
      related diseases including neurodegenerative disorders. An environment enriched
      in intellectual and physical activities can also allay many of the adverse
      effects of aging on the brain. The mechanisms underlying the beneficial effects
      of dietary restriction and environmental enrichment on the brain involve
      stimulation of the expression of neurotrophic factors and 'stress proteins'. The
      neurotrophic factors and stress proteins induced by dietary restriction may
      protect neurons by suppressing oxyradical production, stabilizing cellular
      calcium homeostasis and inhibiting a form of programmed cell death called
      apoptosis. Interestingly, dietary restriction and environmental enrichment also
      increase numbers of newly-generated neural cells in the adult brain suggesting
      that these behavioral modifications can increase the brain's capacity for
      plasticity and self-repair. A better understanding of the cellular and molecular
      mechanisms underlying these effects of diet and behavior on the brain is leading
      to novel therapeutic agents that mimick their beneficial effects.

PMID- 11322998
TI  - Accuracy of magnetic resonance imaging in the diagnosis of deep vein thrombosis
      in asymptomatic patients with injuries of the lower extremity. A pilot study.
AB  - This is a prospective comparative study of magnetic resonance imaging (MRI) of
      the deep veins versus contrast venography in consecutive patients treated for
      various injuries to their lower extremities, showing no clinical symptoms of deep
      vein thrombosis. The majority of examinations referred to in this study were
      performed according to the following methodology: First, the patient was
      subjected to MRI. Subsequently, within a 24-h interval, he/she was subjected to
      contrast venography. The acquired results were compared in a blinded manner. The
      diagnostic indices for MRI were calculated on the assumption that the results of
      contrast venography were sure to give an accurate indication of either presence
      or absence of thrombosis. Thirty-six patients were included in the study, of
      which 27 (15 males) completed it. The overall incidence of distal deep venous
      thrombosis (DVT) was 22% (6/27). One patient showed extension of a crural
      thrombus into the popliteal vein. MRI did not detect any of the thrombi. This
      lack of result was ascribed to failure to fully demonstrate all segments of the
      crural veins. However, MRI did show three proximal thrombi in the superficial
      femoral vein, which were not shown by the venograms. Thus, both the sensitivity
      and specificity of MRI were 0%, so MRI proved to be of no value in the diagnosis
      of asymptomatic deep venous thrombosis in this study.

PMID- 11322999
TI  - Clinical utility of the platelet function analyzer (PFA-100) for the assessment
      of the platelet status in patients with congestive heart failure (EPCOT trial).
AB  - BACKGROUND: Data from small studies have shown the presence of platelet
      abnormalities in patients with congestive heart failure (CHF). We sought to
      characterize the diagnostic utility of platelet function analyzer (PFA-100) in
      the CHF population. METHODS: Blood samples were obtained for measurement of
      adenosine diphosphate (ADP)/collagen and epinephrine/collagen shear-induced
      closure time (CT), whole blood aggregation, platelet contractile force, activity
      of glycoprotein (GP) IIb/IIIa, and P-selectin receptors in 100 consecutive
      outpatients with CHF. RESULTS: Substantial interindividual variability of
      platelet characteristics exists in patients with CHF. There were no statistically
      significant differences when patients were divided by the incidence of vascular
      events, emergency revascularization needs, survival, or etiology of heart
      failure. Aspirin use did not affect instrument readings as well. CT correlates
      well with whole blood aggregometry (r(2)=.587) and less with GP IIb/IIIa activity
      (r(2)=.326). No correlation has been observed for the CT with the platelet-bound
      P-selectin (r(2)=.041) and platelet contractile force measures (r(2)=.028).
      CONCLUSIONS: PFA-100 is indeed capable to serve as a platelet analyzer and may be
      successfully used as a screening device. However, patients with heart failure
      enrolled in the EPCOT trial exhibited a marginal, sometimes oppositely directed
      changes in the platelet function, challenging the diagnostic utility of PFA-100
      to serve as a useful tool for the identification of platelet abnormalities,
      predicting clinical outcomes, or for the monitoring of antiplatelet strategies in
      this population.

PMID- 11323000
TI  - Anti- and procoagulant activities in factor VII-deficient subjects.
AB  - The clinical feature in patients with congenital factor VII deficiency is in part
      dependent on the underlying genetic defect, but the mechanisms influencing the
      genotype-phenotype correlation remain to be fully elucidated. In addition,
      thromboembolic events have been reported. Compensatory mechanisms involving
      vitamin K-dependent factors have been suggested. We have measured anticoagulant
      activities in 25 factor VII-deficient subjects (factor VII activity < or =36%)
      and 23 age-matched controls and correlated these to the vitamin K-dependent
      procoagulant activities. Two of the patients had a history of thromboembolism.
      The factor VII-deficient patients were found to have a significantly lower
      protein C activity than the controls [0.84 U/ml (95% CI 0.78; 0.89) vs. 0.98 U/ml
      (95% CI 0.91; 1.05), P=.004]. In addition, the protein C activity was correlated
      to that of factor VII (r=.36; P=.014), factor IX (r=.45; P=.002) and factor X
      (r=.50; P=.0006), respectively. The level of prothrombin fragment 1+2 was
      correlated to the protein C (r=.40; P=.012) and to the factor VII activity
      (r=.42; P=.011). No differences between patients and controls were seen regarding
      total and free protein S, antithrombin, plasminogen activator inhibitor-1 (PAI-1)
      and tissue factor pathway inhibitor (TFPI). Seven of the patients were found to
      have the Factor V Leiden mutation, but none of them had experienced any
      thromboembolic event. The present data support the notion that compensatory
      hemostatic mechanisms might exist in that the protein C activity was found to be
      decreased in the factor VII-deficient subjects. Whether this could influence the
      clinical feature, including the risk of thromboembolic events in association with
      replacement therapy, remains to be evaluated.

PMID- 11323001
TI  - Early resolution of a life-threatening caval thrombus through percutaneous
      radiological approach.

PMID- 11323002
TI  - Inhibition of platelet aggregation and the release of P-selectin from platelets
      by cilostazol.
AB  - To evaluate the in vitro effects of cilostazol, a phosphodiesterase III
      inhibitor, on platelet responses, we measured platelet aggregation and the levels
      of soluble P-selectin, a glycoprotein present on the alpha-granule membrane in
      resting platelets, and cAMP. Platelet-rich plasma and washed platelets from
      healthy human volunteers were treated with cilostazol (5, 25 and 50 microM).
      Platelet-rich plasma was stimulated by ADP (1 and 5 microM) or collagen (5
      microg/ml). Washed platelets were stimulated by thrombin (4 U/ml) in the presence
      or absence of 1 microM forskolin. In vehicle-treated samples, soluble P-selectin
      levels in response to 1 microM ADP-induced primary aggregation were similar to
      those of circulating levels of healthy volunteers but the levels in response to 5
      microM ADP-induced secondary aggregation and collagen-induced aggregation
      increased markedly compared to those in response to primary aggregation. This
      result suggests that P-selectin is released from platelets according to the
      extent of platelet aggregation. Cilostazol inhibited platelet aggregation as well
      as P-selectin release in a concentration-dependent manner. Cilostazol inhibited
      completely thrombin-induced aggregation in the presence of 1 microM forskolin,
      when cAMP levels were two-fold higher than those in the absence of forskolin.
      Cilostazol, which increases intracellular cAMP in platelets, may be useful in the
      treatment of arterial occlusive diseases.

PMID- 11323003
TI  - Real-time analysis of the interaction of platelets with immobilized
      thrombospondin under flow conditions.
AB  - The platelet granule protein (TS) is extracellularly secreted upon platelet
      activation and then binds to the platelet surface where it can interact with
      various adhesive proteins. Here, we have analyzed platelet interactions with a TS
      coated surface under flow conditions, a model for platelet adhesion onto surface
      bound TS under physiological conditions. Platelets exhibited temporary, very
      short-time adhesion on the TS surface, but no firm adhesion. This adhesion was
      inhibited by NNKY5-5 (anti-glycoprotein (GP) Ib antibody) and AJvW-2 (anti-von
      Willebrand factor (vWF)), indicating that both platelet GP Ib and plasma vWF
      contribute to this interaction. Antibodies against platelet collagen receptor
      integrin alpha(2)beta(1) had no significant effect. These results suggested that
      binding of vWF to TS is the first step in platelet interaction with the TS
      surface. By surface plasmon resonance spectroscopy, a dissociation constant
      (K(d)) of 3.97x10(-7) M was obtained for the binding reaction between immobilized
      TS and vWF. These results suggest the following model for platelet interaction
      with the TS surface under flow: plasma vWF first binds to the immobilized TS and
      then platelets interact with the TS-bound vWF. A low density of bound vWF would
      account for the observed weak interaction between TS and platelets under flow.

PMID- 11323004
TI  - Systemic vascular effects of thrombin and thrombin receptor activating peptide in
      rats.
AB  - The proteolytic enzyme thrombin activates its receptor by cleavage of a peptide
      from the extracellular N-terminus. The newly generated N-terminus acts as a
      tethered ligand to activate the receptor. Receptor-mediated cellular effects of
      thrombin can be mimicked by synthetic peptides, which correspond to the amino
      acid sequence of the newly formed N-terminus. The aim of the present study was to
      investigate vascular effects of thrombin and the thrombin receptor activating
      peptide (TRAP: SFLLRN) in vitro and in vivo in rats. In precontracted rat aortic
      rings, both thrombin (0.3, 1, 3 U/ml) and TRAP (1, 3, 10, 20, 40 microM) induced
      endothelium-dependent relaxant responses. In anaesthetized rats, the mean
      arterial blood pressure (MAP) was measured continuously in the carotid artery by
      a pressure transducer. Thrombin and TRAP were administered as intravenous bolus
      injection via the femoral vein. Thrombin at doses of 3-100 U/kg, as well as TRAP
      at doses of 0.1-0.6 mg/kg i.v., caused a reversible decrease in MAP.
      Administration of TRAP at doses of 0.3 and 0.6 mg/kg led to a triphasic response
      in most of the animals treated (50% and 75%, respectively), i.e. a short drop of
      MAP was followed by an increase and finally a longer lasting decrease in MAP.
      Pretreatment with the nitric oxide (NO)-synthase inhibitor N(G)-nitro-L-arginine
      methylester (L-NAME) suppressed the dose-dependent vasodilator effects of
      thrombin. Heparin and hirudin also inhibited the hypotensive response to
      thrombin. The TRAP-induced triphasic reaction on MAP was not affected by the
      serotonin antagonists ketanserin and tropisetron, as well as the aminopeptidase
      inhibitor amastatin. Pretreatment with L-NAME led to an inhibition of hypotension
      induced by TRAP at 0.1 mg/kg, as well as of the initial transient fall in blood
      pressure at doses of 0.3 and 0.6 mg/kg. The studies suggest that the thrombin-
      and TRAP-induced vasodilation in vitro and in vivo is in part due to the release
      of endothelial NO. In the blood pressure response to TRAP, additional effects
      seem to be involved.

PMID- 11323005
TI  - The effects of oral and intravenous direct thrombin inhibitors on the size of
      photochemically induced cortical infarction in rats.
AB  - Oral thrombin inhibitors are under development as potential drugs for prophylaxis
      and treatment of thrombotic events. The effect of pretreatment with two direct
      thrombin inhibitors, melagatran and inogatran, was evaluated in a rat model of
      cerebral infarction. Ischaemic stroke was induced by photochemical reaction after
      an injection of Rose Bengal and focused posterior and to the right of the
      intersection of the coronal and sagittal sutures on the intact calvarium. A
      single oral dose of melagatran (30 micromol/kg) significantly reduced the volume
      of the cortical infarct by 53% (P<.05) compared with control. In addition,
      following intravenous inogatran (6 micromol/kg) or oral inogatran (100
      micromol/kg), the volume of the cortical infarct decreased by 83% and 19%,
      respectively, compared with control. This study showed that experimental focal
      ischaemic infarction, elicited by photochemically induced endothelial cell
      damage, can be significantly reduced with melagatran and inogatran, direct
      thrombin inhibitors.

PMID- 11323006
TI  - Heparin cofactor II, antithrombin-beta and their complexes with thrombin in human
      tissues.
AB  - In the presence of glycosaminoglycans, thrombin is rapidly inactivated by two
      natural inhibitors secreted from liver: antithrombin (AT) is presumed to be the
      principal thrombin inhibitor in circulating blood, while for heparin cofactor II
      (HCII), a role outside circulation has been proposed. In this study, we show that
      HCII and AT differ with respect to their association with human tissues. Aside
      from brain, each of these inhibitors was found in sodium dodecyl sulphate (SDS)
      soluble extracts of various human organs, with a preponderance of HCII in
      placenta. AT levels, however, predominated in liver. Compared to plasma, the beta
      variant of AT was found to be strongly enriched in human organs, while tissue
      resident HCII did not differ in its electrophoretic mobility from the circulating
      form. In placenta, comparable amounts of HCII/thrombin and AT/thrombin complexes
      were detected, indicating that HCII may exert a thrombin regulating role in that
      organ under conditions of tissue or blood vessel damage. Transcripts coding for
      HCII and AT were detected in all tissues examined. The low levels of their mRNAs
      suggest that most of the tissue-associated thrombin inhibitor molecules originate
      from circulation and are retained in organs, possibly by specific receptors. The
      differential presence of HCII and AT in organs is in accordance with individual
      physiological roles of these inhibitors.

PMID- 11323007
TI  - Pharmacokinetic properties of a novel tissue-type plasminogen activator
      pamiteplase after single intravenous administration to rats, dogs, and monkeys.
AB  - The pharmacokinetics of pamiteplase and recombinant tissue-type plasminogen
      activator (rt-PA) in rats, dogs, and monkeys were examined using a newly
      developed enzyme-linked immunosorbent assay (ELISA). Plasma concentrations after
      intravenous administration of pamiteplase to rats declined in a triphasic manner.
      Plasma concentrations after intravenous administration of pamiteplase to dogs or
      monkeys declined in a biphasic manner. The area under the plasma concentration
      time curve from zero to infinity (AUC(0-->infinity)) in rats and dogs increased
      with increasing dose. The half-life and mean residence time of pamiteplase in
      rats, dogs, and monkeys were shown to be longer than those of rt-PA. Total
      clearance (CL(total)) of pamiteplase was only 7-16% that of rt-PAs, suggesting
      that concentrations of pamiteplase in plasma were higher and more continuous than
      those of rt-PA in these experimental animals. The data suggest that a bolus
      administration of pamiteplase shows the same thrombolytic activity as continuous
      infusion of rt-PA in experimentally induced thrombosis in rats and dogs. The
      pharmacokinetic parameters distribution volume at the steady state and CL(total)
      calculated by immunoreactive concentration after administration of pamiteplase to
      rats, dogs, and monkeys show high correlation with body weights (r(2)=.7728 and
      .9039).

PMID- 11323008
TI  - Molecular modifications in factor VIII concentrates produced from different
      plasma pools.
AB  - We defined the main cause for the increased immunogenicity of the commercial
      factor VIII (fVIII) plasma-derived concentrates reported to induce formation of
      inhibitory antibodies in haemophilia A patients in Germany and Belgium. Formation
      of these antibodies directed against the C2 domain of fVIII was previously
      attributed to the use of solvent/detergent (S/D) treatment and pasteurisation for
      virus inactivation of fVIII concentrate. Since fVIII concentrates associated with
      increased immunogenicity were prepared from plasma pools characterised by
      elevated levels of coagulation markers, we examined whether the plasma source or
      S/D treatment and pasteurisation are responsible for structural changes within
      the C2 domain causing its abnormal immunogenicity. We found that samples of fVIII
      concentrate that originated from the abnormal plasma pool had a reduced ability
      to bind to phospholipid and conformationally sensitive anti-C2 domain antibodies,
      this effect being mostly pronounced in the samples that underwent both S/D
      treatment and pasteurisation. Thus, our study suggests that insufficient quality
      of the starting plasma pools is the major factor determining the structural
      alterations in the C2 domain of fVIII, whereas combination of S/D treatment and
      pasteurisation aggravates these changes.

PMID- 11323009
TI  - Serum lipids and regulation of tissue factor-induced coagulation in middle-aged
      men.
AB  - Formation of an occlusive thrombus by exposure of tissue factor (TF) to
      circulating blood and subsequent triggering of coagulation by TF-activated factor
      VII (FVIIa) complexes on ruptured atherosclerotic plaques is thought to be a key
      event in myocardial infarction. Tissue factor pathway inhibitor (TFPI) is a
      potent inhibitor of TF-induced coagulation in which the anticoagulant function
      most probably is restricted to free TFPI in human plasma. The present study was
      undertaken to assess the interrelations between serum lipids and components of TF
      induced coagulation in 234 apparently healthy men aged 36-56 years recruited from
      the general population. Plasma free TFPI antigen (Ag) was positively correlated
      (P < .001) with total cholesterol, low-density lipoprotein (LDL) cholesterol,
      triglycerides, apolipoprotein B (apoB-100), fibrinogen, total amount of FVII
      (FVIIam), coagulation activity of factor VII (FVIIc), and FVIIa. The significant
      predictors for free TFPI Ag were total cholesterol, triglycerides, fibrinogen,
      FVIIc, and age, which explained 33% of the plasma variation in free TFPI Ag
      assessed by multiple regression analysis. A highly significant (P < .0001) linear
      trend for increase in atherogenic lipids (i.e., total cholesterol and
      triglycerides), FVII (i.e., FVIIc and FVIIa), and fibrinogen across quartiles of
      TFPI Ag was demonstrated after adjustment for confounders. These findings may
      indicate a compensatory increase in plasma free TFPI with lipid and hemostatic
      risk factors for atherothrombotic diseases in healthy middle-aged men.

PMID- 11323010
TI  - A randomized management study of impedance plethysmography vs. contrast
      venography in patients with a first episode of clinically suspected deep vein
      thrombosis.
AB  - OBJECTIVES: In this randomized management study, we examined the safety of
      withholding anticoagulation on the basis of negative impedance plethysmography
      (IPG) compared to negative contrast venography (CV) in symptomatic patients with
      a first episode of clinically suspected deep vein thrombosis (DVT), and we
      determined the impact of the limitations of IPG or CV on their clinical utility.
      METHODS: Patients at a university teaching hospital presenting with a first
      episode of clinically suspected DVT were randomized to one of two management
      strategies at study entry: (1) IPG: if positive, confirmatory CV was performed.
      If CV was positive, anticoagulants were administered, if CV was negative,
      anticoagulants were held. If negative, IPG was repeated serially and if it
      remained negative, anticoagulants were held (n = 165). (2) CV: if positive,
      anticoagulants were administered, if negative, anticoagulants were held (n =
      159). The negative predictive value (NPV) of IPG and CV, positive predictive
      value (PPV) of IPG, and the failure rate of each strategy were assessed. RESULTS:
      Among IPG patients, 28 of 37 with positive IPG initially or during serial testing
      and evaluable CV had confirmed DVT (PPV 76%; 95% confidence interval, CI [62%,
      90%]). DVT was diagnosed during serial testing in 2.1% of patients with initially
      negative IPG who completed testing. The NPV overall of negative IPG was 98.3%.
      During follow-up, two patients in the IPG group (1.2%) and two patients in the CV
      group (1.3%) developed venous thromboembolism (VTE). Death during follow-up
      occurred in 11% of IPG patients compared to 6% of CV patients (P =.13) The
      investigation strategy failed in 25% of IPG patients and in 14% of CV patients.
      CONCLUSIONS: Our findings demonstrate that the two diagnostic strategies we
      studied are equivalent methods for ruling out DVT in patients with a first
      episode of suspected DVT. The PPV of IPG was too low to permit its use alone as a
      test to rule in DVT. Both strategies had surprisingly high failure rates.

PMID- 11323011
TI  - Detection of soluble urokinase receptor by immunoradiometric assay and its
      application in tumor patients.
AB  - It has recently been found that tumor cells express large amounts of urokinase
      receptor (uPAR) on their surface and that the blood soluble uPAR (suPAR) level in
      cancer patients is increased. However, the significance of suPAR in tumor
      progression is still unclear. To investigate the significance of suPAR in
      evaluating clinical status of solid tumor patients, an immunoradiometric assay
      (IRMA) based on using two monoclonal antibodies (McAbs) to different epitopes of
      uPAR was established to determine the serum levels of suPAR in normal individuals
      and solid tumor patients. The detectable range of this suPAR IRMA was 1.95-500
      microg/l. The affinity constant was 4.75x10(9) l/mol. The mean rate of recovery
      was 101.3%, and the mean coefficients of variation for intra- and interassay were
      6.40+/-2.57% (mean+/-S.D., n = 11) and 10.48+/-2.65% (n = 5), respectively. The
      serum suPAR levels were 2.71+/-1.12 microg/l in 62 normal individuals, 3.71+/
      1.69 microg/l in 30 patients with benign tumors, and 5.82+/-2.27 microg/l in 124
      patients with malignant tumors. The serum suPAR levels of these two types of
      tumor patients were increased in comparison with that of normal individuals (P
      values less than.01 and.001). The extent of their increase in malignant tumors
      was much greater than in benign tumors (P < .001). The serum suPAR levels of
      patients with malignant tumors were correlated with tumor invasion, metastasis,
      and surgical intervention. Our data suggest that IRMA for suPAR could be a
      sensitive and specific assay and that the serum suPAR level would be a valuable
      index for evaluating the condition and prognosis of tumor patients in clinic.

PMID- 11323012
TI  - The relationship between the tissue plasminogen activator Alu I/D polymorphism
      and venous thromboembolism during pregnancy.

PMID- 11323013
TI  - In vitro dose response to different GPIIb/IIIa-antagonists: inter-laboratory
      comparison of various platelet function tests.
AB  - AIMS: The aim of this study was to assess the inter- and intra-laboratory
      variation of the concentration-response to the GPIIb/IIIa-antagonists abciximab
      and eptifibatide on platelet aggregometry and to compare results with flow
      cytometric tests as well as the rapid platelet function analyser (RPFA). METHODS:
      In five different laboratory sites, blood from three to five healthy donors was
      spiked with abciximab or eptifibatide, followed by the assessment of: (1)
      aggregometry (anticoagulant: sodium citrate 3.18% or hirudin 5 microg/ml); (2)
      flow cytometry (fibrinogen binding or PAC1-expression), or (3) RPFA. Dose
      response curves were established on the basis of a sigmoidal Imax)-model
      [I=(Imax)*Cg)/(IC50g + Cg)]. RESULTS: For citrated blood, aggregation induced by
      20 microM ADP was blocked up to 100% by both GPIIb/IIIa-antagonists, IC50 values
      varied between 0.11-0.22 microg/ml for eptifibatide and 1.25-2.3 microg/ml for
      abciximab. I(max) of the response to 5 microg/ml collagen ranged from 46% to
      100%, and IC50 values varied between 0.28-0.34 microg/ml for eptifibatide and 2.3
      3.8 microg/ml for abciximab. In hirudinized blood, IC50 values for eptifibatide
      were 1.5- to 3-fold higher than those obtained with citrated plasma. Inhibition
      of PAC1-expression by abciximab (IC50) 0.84 microg/ml) showed results similar
      those of the RPFA (approx. 1.0 microg/ml); larger differences between PAC1 and
      RPFA results were observed for eptifibatide. Based on aggregometry, eptifibatide
      concentrations for 80% inhibition varied from 0.27 to 0.55 microg/ml, and were
      considerably less when the RPFA was taken as basis (0.15 or 0.22 microg/ml). A
      similar pattern was observed for abciximab. CONCLUSIONS: We found quite a low
      inter- and intra-laboratory variation in the in vitro pharmacodynamic
      characterization of GPIIb/IIIa-antagonists by aggregometry, making results of
      these tests obtained from different laboratories during clinical trials at least
      comparable. The RPFA exhibits a higher sensitivity to inhibitory GPIIb/IIIa
      effects, in keeping with the "real" inhibition of the activated receptor (PAC1)
      as assessed with more elaborate flow cytometry.

PMID- 11323014
TI  - Analysis of platelet donors function before and after thrombapheresis using the
      platelet function analyzer PFA-100.

PMID- 11323015
TI  - Enzyme-linked immunosorbent assay for the specific detection of angiostatin-like
      plasminogen moieties in biological samples.
AB  - An enzyme-linked immunosorbent assay (ELISA) was developed for the specific
      detection of human angiostatin-like plasminogen moieties (comprising kringles 1
      4) in biological samples. The assay involves prior removal of all other
      plasminogen moieties by immunoadsorption of diluted samples (to about 10 ng/ml
      plasminogen) with a mixture of insolubilized MA-42B12 (directed against kringle
      5) and MA-31E9 (directed against the proteinase domain). The recovery of
      angiostatin during this procedure is > or = 95%. Subsequently, angiostatin-like
      fragments are detected in an ELISA, based on two monoclonal antibodies reacting
      with nonoverlapping epitopes in the kringle 1-3 domain: MA-36E6 for capture and
      MA-34D3 for tagging. The assay has a lower detection limit of about 0.1 ng/ml and
      is performed with intra- and interassay coefficient of variation of 2.4% and 15%.
      In tumor fluids obtained from cancer patients (n = 10), angiostatin levels ranged
      between 0.24 and 6.7 microg/ml (1.62+/-0.60 microg/ml; mean+/-S.E.M.) The
      identity of angiostatin was confirmed by immunoblotting using specific monoclonal
      antibodies. A weak correlation (r = .66) was observed with the total plasminogen
      concentration in these samples. This ELISA thus appears suitable for the specific
      quantitation of angiostatin-like plasminogen moieties in biological samples, and
      may be useful to study its (patho)physiological relevance.

PMID- 11323016
TI  - Matrix metalloproteinase deficiencies do not impair cell-associated fibrinolytic
      activity.
AB  - The matrix metalloproteinase (MMP) and fibrinolytic (plasminogen/plasmin) systems
      cooperate in many (patho)physiological processes requiring extracellular
      proteolysis. The effect of MMP-3 (stromelysin-1), MMP-7 (matrilysin), MMP-9
      (gelatinase B) or MMP-12 (metalloelastase) on cellular fibrinolytic activity was
      studied with the use of smooth muscle cells (SMC) and fibroblasts derived from
      mice with specific inactivation of these genes. Activation of cell-bound
      plasminogen by two-chain urokinase-type plasminogen activator (tcu-PA) was not
      significantly different with SMC or fibroblasts from the gene-deficient mice (78%
      to 140% of wild-type). For all cell types, very limited conversion of plasminogen
      to angiostatin-like kringle-containing fragments was observed (< 3% of the total
      cell-bound plasminogen). Activation of plasminogen in solution by cell-associated
      tcu-PA was also comparable for SMC or fibroblasts of the different genotypes (54%
      to 160% of wild-type). In vitro SMC migration on scrape wounded collagen-coated
      surfaces was comparable for wild-type, MMP-7(-/-), MMP-9(-/-) and MMP-12(-/-)
      SMC, but was significantly reduced for MMP-3(-/-) SMC (P < .005 vs. wild-type).
      Serum-free conditioned medium of MMP-3(-/-) and MMP-7(-/-) SMC or fibroblasts
      induced similar lysis of fibrin films as wild-type cells. These findings indicate
      that several interactions that have been described between these MMPs and the
      plasminogen/plasmin system in a purified system do not significantly affect
      plasmin-mediated cellular fibrinolytic activity under cell culture conditions.

PMID- 11323017
TI  - Suppressing thrombin generation is compatible with the development of
      atherosclerosis in mice.
AB  - Thrombin has been proposed to play a key role in the development of
      atherosclerosis, both by promoting fibrin deposition into the atherosclerotic
      vessel wall and also by signalling through thrombin receptors. Unfortunately,
      mice homozygous for a deletion of the prothrombin gene (FII) die in utero, making
      a direct assessment of the role of thrombin during atherogenesis difficult. We
      have assessed the contribution of thrombin-dependent processes to vascular lipid
      lesion formation in the atherosclerosis-prone apolipoprotein E (ApoE)-deficient
      mice by inhibiting thrombin generation with warfarin. ApoE-/- mice were treated
      with warfarin at a dose that increased the prothrombin time (PT) more than 10
      fold (250-375 microg/kg body weight/day) for 12 weeks from the age of 12 weeks
      onwards. The extent and composition of the vascular lipid lesions that developed
      were assessed using oil red O to measure neutral lipid in the vessel wall and
      quantitative immunofluoresence to measure fibrin(ogen) levels as well as
      macrophage and smooth muscle cell numbers. Mice treated with warfarin developed
      lesions both in the aortic sinus and the descending aorta to the same degree as
      mice receiving no treatment (28,351+/-350 microm2/mouse treated with warfarin
      versus 27,952+/-750 micro2/control mouse; P = .86). However, the amount of
      fibrin(ogen) deposited in the vessel wall was decreased by more than 60% (34+/-11
      arbitrary units in warfarin treated mice versus 92+/-11 arbitrary units in
      control mice; P < .01). Staining of macrophage and for smooth muscle cell markers
      was unaltered by treatment with warfarin. We conclude that suppressing thrombin
      generation does not alter the development of vascular lipid lesions in mice with
      a severe disorder of lipid metabolism, despite a marked reduction in fibrin(ogen)
      deposition.

PMID- 11323018
TI  - Evaluation of a sensitive colorimetric FXIII incorporation assay. Effects of
      FXIII Val34Leu, plasma fibrinogen concentration and congenital FXIII deficiency.
AB  - There is an increasing interest in the role of coagulation factor XIII (FXIII) in
      cardio- and cerebrovascular diseases. It has recently been reported that a common
      G-->T point mutation in the A-subunit gene of FXIII, which codes for a valine
      (val) to leucine (leu) change (FXIIIVal34Leu), is protective against thrombotic
      diseases but seems to increase the risk of intracerebral bleeding. We developed a
      colorimetric incorporation assay for detection of FXIII activity based on
      incorporation of 5-(biotinamido) pentylamine (BAPA) into fibrin or fibrinogen.
      With this new assay, we studied the effects of FXIIIVal34Leu mutation, plasma
      fibrinogen concentration and congenital FXIII deficiency on FXIII activity. There
      are no data available about the ability of different FXIII assays to detect
      altered activity in FXIIIVal34Leu genotypes. We therefore compared our results
      determined by the incorporation method with a commonly used photometric method
      based on ammonia release after cross-linking of glycine-ethylester to a specific
      glutamine containing peptide substrate. We also determined FXIII A-subunit
      antigen (Ag) levels using enzyme-linked immunosorbent assay (ELISA) technique.
      The FXIIIVal34Leu genotype could not be detected either by the photometric method
      nor by the FXIII A-subunit ELISA. The incorporation assay showed an increased
      specific FXIII activity in subjects possessing the leu allele. The photometric
      assay and ELISA gave similar results independent from genotype. In patients with
      congenital FXIII deficiency before and after substitution, however, ELISA and the
      incorporation assay gave similar results, whereas the photometric assay showed
      consistently higher values. Our results show that the incorporation assay, not
      the photometric assay based on ammonia release, can be used for detection of
      elevated activity in subjects with FXIIIVal34Leu. Because of specificity and over
      a wide range sensitivity, the assay can also be used for determination of FXIII
      deficiency and monitoring of FXIII substitution therapy.

PMID- 11323019
TI  - Time course of recovery and complications of HELLP syndrome with two different
      treatments: heparin or dexamethasone.
AB  - HELLP syndrome is a severe complication of pregnancy characterized by
      microangiopathic hemolytic anemia, hepatic dysfunction and thrombocytopenia.
      Though delivery is the ultimate therapeutic option, medical treatments, including
      the use of heparin or corticosteroids, have been employed in the attempt to
      improve maternal prognosis. The aim of this retrospective study was to compare
      the time course of recovery and the incidence of complications in women with
      HELLP syndrome receiving either heparin or dexamethasone. Between January 1990
      and December 1998, 32 patients with HELLP syndrome were cared for at the
      Institute of Obstetrics and Gynecology of the University of Florence: 20 patients
      were treated with heparin, administered subcutaneously at a dose of 5000 IU every
      12 h, whereas 12 women received dexamethasone, administered intravenously at a
      dose of 10 mg every 12 h. Categorical data were evaluated with chi-square and
      Fisher's exact test; continuous data were analyzed with Mann-Whitney U test; P <
      .05 was considered significant. In the subgroup treated with heparin the
      incidence of disseminated intravascular coagulation (DIC) (P < .02), the number
      of patients requiring blood transfusion (P < .05) and the length of stay at the
      Intensive Care Unit (ICU) (P < .04) were significantly increased as compared with
      the subgroup receiving dexamethasone; in this latter subgroup, significantly
      higher platelet count and hematocrit values, and significantly lower levels of
      lactate dehydrogenase (LDH) could be documented starting from day 2 after
      delivery. The results of our investigation suggest that the use of dexamethasone
      in patients with HELLP syndrome is associated with faster regression and lower
      incidence of complications in comparison to heparin.

PMID- 11323020
TI  - Endothelial dysfunction, nitric oxide and platelet activation in hypertensive and
      diabetic type II patients.
AB  - Alterations in the synthesis or enhanced inactivation of nitric oxide (NO) and an
      increase in endothelin-1 production lead to an imbalance that can induce arterial
      hypertension. Type II diabetes is characterized by impaired endothelium-dependent
      vasodilation and vascular disease. NO is produced through L-arginine pathway by
      three different isoforms of nitric oxide synthase (NOS), an inducible form that
      can be activated by cytokines such as tumor necrosis factor alpha (TNFalpha). We
      evaluated NO plasmatic levels, endothelial damage markers such as von Willebrand
      factor (vWF), platelet activation, soluble P-selectin (sP-Sel), TNFalpha levels,
      insulinaemia (I), glycosylated haemoglobin (HbA1c), glycaemia and blood pressure
      in 32 hypertensive diabetic type II patients (Group A), 37 hypertensive patients
      (Group B) and 35 healthy subjects (Group C) matched in sex, age, body mass index
      and dietary habits. The level of I was increased in patients compared to the
      controls and correlated with their NO levels. vWF plasmatic levels were increased
      in Group A compared to Groups B and C. We also found significant differences in
      platelet activation among all the groups. In diabetic patients, increased NO
      levels correlated with TNFalpha, HbA1c and platelet activation showed greater
      endothelial damage than in Group B. These parameters described a prothrombotic
      state associated with an insulin resistance state, an increased vWF release,
      raised sP-Sel and TNFalpha levels and, maybe, low NO bioavailability, which could
      lead to a higher risk of development of thrombotic events in hypertensive
      diabetic patients (Group A) than in the hypertensive patients in Group B.

PMID- 11323021
TI  - Common mutations at the homocysteine metabolism pathway and pediatric stroke.
AB  - Heterozygosity and/or homozygosity for mutations at the genes of the enzymes
      involved in homocysteine metabolism may confer an increased risk for thrombosis
      by causing hyperhomocysteinemia. Although the mutations related to homocysteine
      metabolism possibly increase the risk of stroke, the data are conflicting and
      there are very few reports linking these defects to acute stroke in children. We
      aimed to study the role of these mutations in Turkish children with ischemic
      stroke. Forty-six patients having cerebral infarct were clinically diagnosed, and
      the infarction verified with magnetic resonance imaging of the brain was included
      in the study. All patients were below the age of 18 (10 months to 18 years).
      Sixty-eight controls, consecutively selected among healthy unrelated subjects
      from the same geographic area of Turkey without personal and family history of
      thrombosis, stroke or Behest's disease, were included. Genotyping for the common
      mutations was carried out by the methods described previously. There was no
      difference between the pediatric stroke patients and controls for the
      distribution of methylene tetrahydrofolate reductase (MTHFR) 677 C-T, MTHFR 1298
      A-C, methylene tetrahydrofolate dehydrogenase (MTHFD) 1958 G-A and methionine
      synthase reductase (MTRR) 66 A-G alleles. There was no risk for double gene
      alterations (MTHFR 677 C-T vs. 1298 A-C) after individuals with FV 1691 A
      mutation is excluded. Twelve of the 46 patients were found to carry FV 1691 A
      mutation (26.0%), one being homozygote. The cerebral infarct risk for FV 1691 A
      was found to be 6.4 (CI 95% 1.7-23.0). Eight of the 46 patients were found to
      carry PT 20210 A mutation (16.6%). Two of the FV 1691 A heterozygous patients
      carried PT 20210 A mutation at the same time (4.2%). As a conclusion, we can say
      that FV 1691 A and PT 20210 A mutations are important and must be included to the
      routine analysis of pediatric stroke patients.

PMID- 11323022
TI  - The alpha2 Gene alleles of the platelet collagen receptor integrin alpha2 beta1
      in Turkish children with cerebral infarct.
AB  - The possible role of point mutations in the platelet integrin alpha2 beta1 gene
      in Turkish children with ischemic stroke was evaluated in this study. The case
      control study included 44 pediatric patients with cerebral infarct (age range, 10
      months to 18 years) and 96 healthy unrelated individuals. Genotyping was
      performed according to previously described methods. Distribution of the three
      haplotypes were 36.4%, 45.3%, 10.4% and 31.8%, 50.0%, 13.6% for the controls and
      the patients, respectively. A new fourth haplotype was found which was 7.8% and
      4.5% respectively. Our data indicated that these haplotypes are not risk factors
      in pediatric stroke group.

PMID- 11323023
TI  - Diagnostic value of the D-dimer test in deep vein thrombosis: improved results by
      a new assay method and by using discriminate levels.
AB  - Previous studies have suggested that D-dimer testing reliably selects patients
      for whom duplex sonography should be performed for diagnosis of deep vein
      thrombosis (DVT). However, the interassay correlation is poor. Therefore, we
      tested four D-dimer methods for their ability to rule out DVT, including the
      Miniquant test, a new D-dimer assay method. Sensitivity, specificity, negative
      predictive value (NPV) and positive predictive value (PPV) were calculated vs.
      duplex sonography. Twenty-nine of 108 (27%) patients with suspected DVT were
      diagnosed as having DVT by sonography. The Vidas enzyme-linked immunoabsorbent
      assay (ELISA) test, the Miniquant turbidimetric test and the latex agglutination
      test for D-dimer all provided discriminate values for achieving 100% sensitivity
      and 100% NPV. D-dimer results demonstrated higher specificity and PPV in the
      outpatient vs. the inpatient group. This probably reflects the higher proportion
      of inpatients with comorbid conditions, such as malignancy and postsurgery
      status, in whom D-dimer results show very poor specificity and PPV. The new
      Miniquant turbidimetric assay performed as well as the more established ELISA
      method. We conclude that the D-dimer tests were shown to possess the necessary
      sensitivity and NPV to be useful in screening patients with suspected DVT. A
      negative D-dimer test in selected patients could be helpful in reducing the
      number of sonograms performed for diagnosis of DVT.

PMID- 11323024
TI  - Glycoprotein Ib/IX/V binding to the membrane skeleton maintains shear-induced
      platelet aggregation.
AB  - The extracellular domain of glycoprotein (Gp) Ibalpha serves as the von
      Willebrand factor (vWf) receptor that triggers shear stress-dependent platelet
      aggregation. Its intracellular domain associates with actin-binding protein-280
      (filamin 1a) that binds directly to filamentous actin, thereby linking the
      membrane skeleton to GpIbalpha. We examined the functional significance of
      GpIbalpha interactions with actin during platelet aggregation in response to 120
      dyn/cm(2) shear stress. Lysates of resting and sheared platelets were centrifuged
      at approximately 13,000xg for 15 min, and GpIbalpha was immunoprecipitated from
      the lysate supernatant. GpIbalpha and coimmunoprecipitated proteins were
      separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE)
      and immunoblotted with antibodies specific for GpIbalpha and actin. We observed a
      significant increase in the amounts of actin coimmunoprecipitating with GpIbalpha
      as platelets aggregated in response to shear stress. Actin/GpIbalpha interactions
      reached a maximum after 90 s of shear stress. Monoclonal antibody (mAb) blockade
      of vWf binding to GpIbalpha inhibited shear stress-induced platelet aggregation
      and actin associating with GpIbalpha. Pretreatment of platelets with cytochalasin
      D resulted in the inhibition of actin binding to GpIbalpha in sheared platelets
      and in an increase in the rate and magnitude of platelet disaggregation. These
      data indicate that shear stress causes changes in the association between
      GpIbalpha and the actin-based membrane skeleton. The increased interaction
      between GpIbalpha and the actin-based membrane skeleton results from shear
      induced vWf binding to GpIbalpha and is mechanoprotective in that it maintains
      shear-induced aggregation of activated platelets.

PMID- 11323025
TI  - Inhibition of tissue factor-activated platelets by low-molecular-weight heparins
      and glycoprotein IIb/IIIa receptor antagonist.
AB  - Thrombotic disorders can lead to vascular distress and platelet activation
      eventually resulting in the rupture of the lesions where a sizable amount of
      tissue factor (TF) is generated during the pathogenesis of arterial diseases.
      Since low-molecular-weight heparins (LMWHs) and platelet glycoprotein (GP)
      IIb/IIIa inhibitors are clinically used for the management of acute coronary
      syndrome (ACS), studies were taken to determine the effects of these agents on TF
      mediated activation of platelets. Freshly drawn native whole blood (WB) from
      normal healthy volunteers (n = 6) supplemented with a predetermined amount of TF
      was incubated with equivalent anti-Xa adjusted amounts of various LMWHs at 0.01
      1.0 U/ml and tirofiban from 10 to 100 ng/ml. Platelet activation was assessed by
      measuring the expression of P-selectin (CD62) and the generation of platelet
      aggregates. At 0.01 U/ml, enoxaparin exhibited a stronger inhibition of TF
      induced platelet activation compared to ardeparin and dalteparin. At 0.1 U/ml,
      these LMWHs produced a comparable inhibition of total P-selectin expression, and
      at 1.0 U/ml, a marked inhibition was noted. Since enoxaparin produced the best
      concentration-dependent inhibition of P-selectin expression (saline: 76 +/- 10%
      vs. 1.0 U/ml enoxaparin: 18 +/- 7%; P < .02) and platelet aggregate formation
      (saline: 63 +/- 7% vs. 1.0 U/ml enoxaparin: 35 +/- 6%, P < .035), this agent was
      used for additional studies. Unlike enoxaparin, tirofiban produced a weak
      concentration-dependent inhibition of platelet activation. At 100 ng/ml,
      tirofiban produced a 40% inhibition of P-selectin expression and about 60%
      inhibition of platelet aggregate formation. To elucidate the potential
      interaction between tirofiban and enoxaparin, the effect of 10 and 100 ng/ml
      tirofiban was studied with enoxaparin-supplemented WB in a 0.01-1.0 U/ml range.
      Additive effects between these two agents were noted only at lower
      concentrations. Thus, at therapeutic concentrations (0.8-1.2 U/ml), enoxaparin
      itself was capable of inhibiting TF-mediated activation of platelets to > 70%;
      whereas tirofiban failed to produce such concentration-dependent inhibition. This
      suggests that the simultaneous administration of GPIIb/IIIa receptor antagonist
      with LMWH may not have any added benefit in the clinical management of patients
      with ACS.

PMID- 11323026
TI  - Selective recognition of alpha2beta1 integrin by jararhagin, a
      Metalloproteinase/disintegrin from bBothrops jararaca venom.

PMID- 11323027
TI  - A comparison of the antiplatelet effect of S-nitrosoglutathione in whole blood
      and platelet-rich plasma.

PMID- 11323028
TI  - Inactivation of thrombin by a fucosylated chondroitin sulfate from echinoderm.
AB  - A polysaccharide extracted from the sea cucumber body wall has the same backbone
      structure as the mammalian chondroitin sulfate, but some of the glucuronic acid
      residues display sulfated fucose branches. These branches confer high
      anticoagulant activity to the polysaccharide. Since the sea cucumber chondroitin
      sulfate has analogy in structure with mammalian glycosaminoglycans and sulfated
      fucans from brown algae, we compared its anticoagulant action with that of
      heparin and of a homopolymeric sulfated fucan with approximately the same level
      of sulfation as the sulfated fucose branches found in the sea cucumber
      polysaccharide. These various compounds differ not only in their anticoagulant
      potencies but also in the mechanisms of thrombin inhibition. Fucosylated
      chondroitin sulfate, like heparin, requires antithrombin or heparin cofactor II
      for thrombin inhibition. Sulfated fucans from brown algae have an antithrombin
      effect mediated by antithrombin and heparin cofactor II, plus a direct
      antithrombin effect more pronounced for some fractions. But even in the case of
      these two polysaccharides, we observed some differences. In contrast with
      heparin, total inhibition of thrombin in the presence of antithrombin is not
      achieved with fucosylated chondroitin sulfate, possibly reflecting a less
      specific interaction. Fucosylated chondroitin sulfate is able to inhibit thrombin
      generation after stimulation by both contact-activated and thromboplastin
      activated systems. It delayed only the contact-induced thrombin generation, as
      expected for an anticoagulant without direct thrombin inhibition. Overall, the
      specific spatial array of the sulfated fucose branches in the fucosylated
      chondroitin sulfate not only confer high anticoagulant activity to the
      polysaccharide but also determine differences in the way it inhibits thrombin.

PMID- 11323029
TI  - The interaction of the calcium- and integrin-binding protein (CIBP) with the
      coagulation factor VIII.
AB  - The gene encoding the C-terminal part of A1-domain of human blood coagulation
      factor VIII (FVIII), a 110-amino acid fragment from Ala(227) to Arg(336), namely
      A1(Delta1-226), was cloned and used as a 'bait' to screen a protein, which might
      interact with this region by using the yeast two-hybrid system. A gene coding for
      a related protein of FVIII named calcium- and integrin-binding protein (CIBP) was
      isolated from the normal human liver cDNA library. The results were confirmed by
      using the mammalian two-hybrid system and coimmunoprecipitation. The gene coding
      for CIBP was constructed by polymerase chain reaction (PCR) and then
      cotransfected with the B-domain-deleted FVIII gene into mammalian cell lines
      using the expression vector of FVIII for transient or stable expression. The
      culture supernatant was collected and analyzed both by enzyme-linked
      immunosorbent assay (ELISA) for FVIII antigen level and by one-stage method for
      procoagulant activity. Coexpressed with CIBP, the antigen level of FVIII in the
      mammalian cell line baby hamster kidney (BHK) cells increased up to about 170%
      and its bioactivity rose accordingly.

PMID- 11323030
TI  - Aluminum toxicity studies in Vaucheria longicaulis var. macounii (Xanthophyta,
      Tribophyceae). I. Effects on cytoplasmic organization.
AB  - Using differential interference contrast (DIC) and epifluorescence microscopy, we
      tested the hypothesis that exposure to environmentally significant levels of
      aluminum (Al) would cause rapid changes in cytoplasmic organization in vegetative
      filaments of the coenocytic alga, Vaucheria longicaulis Hoppaugh var. macounii
      Blum resulting in the loss of cytoplasmic streaming. In untreated cells, DIC
      microscopy revealed the presence of cortical cytoplasmic strands that were
      oriented longitudinally to the cell axis as well as sub-cortical cytoplasmic
      strands that exhibited a reticulate morphology. Organelles such as chloroplasts
      and mitochondria translocated throughout the cell in close association with the
      cortical longitudinal cytoplasmic strands. Staining with the lipophilic dye, 3,3
      dihexyloloxacarbocyanine, revealed structures that appeared to be endoplasmic
      reticulum (ER). This organelle closely resembled, in location and appearance, the
      cytoplasmic strands visualized using DIC microscopy. The addition of Al (80 uM)
      resulted in the inhibition of cytoplasmic streaming as well as the dissipation of
      the putative cortical longitudinal ER within one minute. Subsequently, the DIC
      visible cortical cytoplasmic strands exhibited progressive degrees of
      disorganization. Throughout these changes, chloroplasts and mitochondria remained
      visibly associated with the cortical cytoplasmic strands.

PMID- 11323031
TI  - Aluminum toxicity studies in Vaucheria longicaulis var. macounii (Xanthophyta,
      Tribophyceae). II. Effects on the F-actin array.
AB  - In this study, we test the hypothesis that exposure to environmentally
      significant concentrations of aluminum (Al, 80 uM) causes the microfilament array
      of Vaucheria longicaulis var. macounii vegetative filaments to become fragmented
      and disorganized. Changes in F-actin organization following treatment of
      vegetative filaments by Al are examined using vital staining with fluorescein
      phalloidin. In the cortical cytoplasm of the apical zone of pH 7.5 and pH 4.5
      control cells, axially aligned bundles of F-actin lead to a region of diffuse,
      brightly stained material. Dimly stained focal masses are noted deeper in the
      cytoplasm of the apical zone whereas they are absent from the zone of
      vacuolation. The F-actin array is visualized in the cortical cytoplasm of the
      region of the cell, distal to the apical tip, which exhibits vigorous cytoplasmic
      streaming (zone of vacuolation) as long, axially aligned bundles with which
      chloroplasts and mitochondria associate. Thirty minutes following treatment with
      aluminum, and for the next 8-16 h, the F-actin array is progressively
      disorganized. The longitudinally aligned F-actin array becomes fragmented.
      Aggregates of F-actin, such as short rods, amorphous and stellate F-actin focal
      masses, curved F-actin bundles and F-actin rings replace the control array. Each
      of these structures may occur in association with chloroplasts or independently
      with no apparent association with organelles. Images are recorded which indicate
      that F-actin rings not associated with organelles may self-assemble by successive
      bundling of F-actin fragments. The fragmentation and bundling of F-actin in cells
      of V. longicaulis upon treatment with aluminum resembles those reported after
      diverse forms of cell disturbance and supports the hypothesis that aluminum
      induced changes in the F-actin array may be a calcium-mediated response to
      stress.

PMID- 11323032
TI  - Water transport in trees: current perspectives, new insights and some
      controversies.
AB  - This review emphasizes recent developments and controversies related to the
      uptake, transport and loss of water by trees. Comparisons of the stable isotope
      composition of soil and xylem water have provided new and sometimes unexpected
      insights concerning spatial and temporal partitioning of soil water by roots.
      Passive, hydraulic redistribution of water from moister to drier portions of the
      soil profile via plant root systems may have a substantial impact on vertical
      profiles of soil water distribution, partitioning of water within and among
      species, and on ecosystem water balance. The recent development of a technique
      for direct measurement of pressure in individual xylem elements of intact,
      transpiring plants elicited a number of challenges to the century-old cohesion
      tension theory. The ongoing debate over mechanisms of long-distance water
      transport has stimulated an intense interest in the phenomenon and mechanisms of
      embolism repair. Rather than embolism being essentially irreversible, it now
      appears that there is a dynamic balance between embolism formation and repair
      throughout the day and that daily release of water from the xylem via cavitation
      may serve to stabilize leaf water balance by minimizing the temporal imbalance
      between water supply and demand. Leaf physiology is closely linked to hydraulic
      architecture and hydraulic perturbations, but the precise nature of the signals
      to which stomata respond remains to be elucidated. When water transport in trees
      is studied at multiple scales from single leaves to the whole organism,
      considerable functional convergence in regulation of water use among
      phylogenetically diverse species is revealed.

PMID- 11323033
TI  - Advancing fine root research with minirhizotrons.
AB  - Minirhizotrons provide a nondestructive, in situ method for directly viewing and
      studying fine roots. Although many insights into fine roots have been gained
      using minirhizotrons, a review of the literature indicates a wide variation in
      how minirhizotrons and minirhizotron data are used. Tube installation is
      critical, and steps must be taken to insure good soil/tube contact without
      compacting the soil. Ideally, soil adjacent to minirhizotrons will mimic bulk
      soil. Tube installation causes some degree of soil disturbance and has the
      potential to create artifacts in subsequent root data and analysis. We therefore
      recommend a waiting period between tube installation and image collection of 6-12
      months to allow roots to recolonize the space around the tubes and to permit
      nutrients to return to pre-disturbance levels. To make repeated observations of
      individual roots for the purposes of quantifying their dynamic properties (e.g.
      root production, turnover or lifespan), tubes should be secured to prevent
      movement. The frequency of image collection depends upon the root parameters
      being measured or calculated and the time and resources available for collecting
      images and extracting data. However, long sampling intervals of 8 weeks or more
      can result in large underestimates of root dynamic properties because more fine
      roots will be born and die unobserved between sampling events. A sampling
      interval of 2 weeks or less reduces these underestimates to acceptable levels.
      While short sample intervals are desirable, they can lead to a potential trade
      off between the number of minirhizotron tubes used and the number of frames
      analyzed per tube. Analyzing fewer frames per minirhizotron tube is one way to
      reduce costs with only minor effects on data variation. The quality of
      minirhizotron data should be assessed and reported; procedures for quantifying
      the quality of minirhizotron data are presented here. Root length is a more
      sensitive metric for dynamic root properties than the root number. To make
      minirhizotron data from separate experiments more easily comparable,
      idiosyncratic units should be avoided. Volumetric units compatible with
      aboveground plant measures make minirhizotron-based estimates of root standing
      crop, production and turnover more useful. Methods for calculating the volumetric
      root data are discussed and an example presented. Procedures for estimating fine
      root lifespan are discussed.

PMID- 11323034
TI  - The tightening grip of big pharma.

PMID- 11323035
TI  - Carotid endarterectomy and prevention of stroke in the very elderly.

PMID- 11323038
TI  - Identification and prevention of work-related carpal-tunnel syndrome.

PMID- 11323039
TI  - Assessment of value of consensus definitions in acute variceal bleeding.

PMID- 11323040
TI  - Sexual health education for male sex workers.

PMID- 11323041
TI  - Probability of HIV-1 transmission per coital act in monogamous, heterosexual, HIV
      1-discordant couples in Rakai, Uganda.
AB  - BACKGROUND: The probability of HIV-1 transmission per coital act in
      representative African populations is unknown. We aimed to calculate this
      probability overall, and to estimate how it is affected by various factors
      thought to influence infectivity. METHODS: 174 monogamous couples, in which one
      partner was HIV-1 positive, were retrospectively identified from a population
      cohort in Rakai, Uganda. Frequency of intercourse and reliability of reporting
      within couples was assessed prospectively. HIV-1 seroconversion was determined in
      the uninfected partners, and HIV-1 viral load was measured in the infected
      partners. Adjusted rate ratios of transmission per coital act were estimated by
      Poisson regression. Probabilities of transmission per act were estimated by log
      log binomial regression for quartiles of age and HIV-1 viral load, and for
      symptoms or diagnoses of sexually transmitted diseases (STDs) in the HIV-1
      infected partners. RESULTS: The mean frequency of intercourse was 8.9 per month,
      which declined with age and HIV-1 viral load. Members of couples reported similar
      frequencies of intercourse. The overall unadjusted probability of HIV-1
      transmission per coital act was 0.0011 (95% CI 0.0008-0.0015). Transmission
      probabilities increased from 0.0001 per act at viral loads of less than 1700
      copies/mL to 0.0023 per act at 38 500 copies/mL or more (p=0.002), and were
      0.0041 with genital ulceration versus 0.0011 without (p=0.02). Transmission
      probabilities per act did not differ significantly by HIV-1 subtypes A and D,
      sex, STDs, or symptoms of discharge or dysuria in the HIV-1-positive partner.
      INTERPRETATION: Higher viral load and genital ulceration are the main
      determinants of HIV-1 transmission per coital act in this Ugandan population.

PMID- 11323042
TI  - Risk, causes, and prevention of ischaemic stroke in elderly patients with
      symptomatic internal-carotid-artery stenosis.
AB  - BACKGROUND: Carotid endarterectomy benefits patients with symptomatic stenosis of
      70-99% in the internal carotid artery, with smaller benefit for 50-69% stenosis.
      The benefit of carotid endarterectomy in patients of 75 years and older remains
      unclear. METHODS: Patients aged 75 years or older from the North American
      Symptomatic Carotid Endarterectomy Trial were compared with those aged 65-74
      years and less than 65 years for baseline characteristics and risk of ipsilateral
      ischaemic stroke at 2 years by degree of stenosis and treatment group. FINDINGS:
      Among patients with 70-99% stenosis, the absolute risk reduction of ipsilateral
      ischaemic stroke with carotid endarterectomy was 28.9% (95% CI 12.9-44.9) for
      patients aged 75 years or older (n=71), 15.1% (7.2-23.0) for those aged 65-74
      years (n=285), and 9.7% (1.5-17.9) for the youngest group (n=303). Among patients
      with 50-69% stenosis, the absolute risk reduction was significant only in those
      of 75 years and older (n=145; 17.3% [6.6-28.0]). The perioperative risk of stroke
      and death at any degree of stenosis was 5.2% for the oldest group, 5.5% for 65-74
      years, and 7.9% for less than 65 years. The number of patients aged 75 years or
      older needed to treat to prevent one ipsilateral stroke within 2 years was three
      with 70-99% stenosis and six with 50-69% stenosis. INTERPRETATION: In the
      prevention of ipsilateral ischaemic stroke, elderly patients with 50-99%
      symptomatic carotid stenosis benefited more from carotid endarterectomy than
      younger patients did. To achieve this treatment benefit, surgeons must be skilled
      and patients with other life-threatening illnesses must be excluded.

PMID- 11323043
TI  - The burden of reproductive-organ disease in rural women in The Gambia, West
      Africa.
AB  - BACKGROUND: Data on the epidemiology of reproductive-organ morbidity are needed
      to guide effective interventions, to set health-care priorities, and to target
      future research. This study aimed to find out the prevalence of reproductive
      organ disease in a sample of rural Gambian women. METHODS: A questionnaire on
      reproductive health was administered by fieldworkers to women aged 15-54 years
      living in a rural area under demographic surveillance. A female gynaecologist
      questioned and examined the women (including speculum and bimanual pelvic
      examinations). Vaginal swabs were taken to test for Trichomonas vaginalis,
      Candida albicans, and bacterial vaginosis, cervical smears for cytology, cervical
      swabs for Chlamydia trachomatis PCR and Neisseria gonorrhoeae culture, and venous
      blood for haemoglobin, HIV, herpes simplex virus 2, and syphilis serology.
      FINDINGS: 1348 (72.0%) of 1871 eligible women took part. Reproductive-organ
      symptoms were more likely to be reported to the gynaecologist (52.7% of women)
      than to the fieldworker (26.5%). Menstrual problems, abnormal vaginal discharge,
      and vaginal itching were the most commonly reported symptoms. A minority of women
      said they had sought health care for their symptoms. The frequencies of
      reproductive-organ morbidity were high: menstrual dysfunction 34.1% (95% CI 29.6
      39.1), infertility 9.8% (8.2-11.6), reproductive-tract infections 47.3% (43.7
      51.0), pelvic tenderness 9.8% ((7.0-13.5), cervical dysplasia 6.7% (5.2-8.4),
      masses 15.9% (12.5-20.1), and childbirth-related damage to pelvic structures
      46.1% (40.1-52.3). 948 (70.3%) women had at least one reproductive-organ
      disorder. INTERPRETATION: For these rural women, whose lives depend heavily on
      their reproductive function, reproductive-organ disease is a large burden. In
      inadequately resourced rural areas, with poor education, heavy agricultural and
      domestic labour, and limited access to quality health care, many women are not
      able to attain and maintain reproductive health and wellbeing.

PMID- 11323044
TI  - Lay constructions of a family history of heart disease: potential for
      misunderstandings in the clinical encounter?
AB  - BACKGROUND: Family history is recognised as a risk factor for coronary heart
      disease (CHD) by epidemiologists, health professionals, and the public, and could
      act either as a spur or barrier to changing health behaviour. However, there has
      been no systematic investigation of which factors affect whether people regard
      themselves as having a family history of CHDor not. METHODS: We used purposive
      sampling to select 61 men and women who were middle class or working class from a
      large cross-sectional survey. Half the respondents had indicated in this previous
      survey that they had heart disease in their family. The range of understanding of
      the meaning of having a family history was explored in detailed qualitative
      semistructured interviews. FINDINGS: Perception of a family history of heart
      disease depended on knowledge of the health of family members, the number and
      closeness of relatives with heart conditions, the age of affected relatives, and
      the respondent's sex and social class. Men, particularly working-class men,
      required a greater number of close relatives to be affected to perceive that they
      had a family history. Even when respondents judged that heart disease ran in
      their family, they did not always perceive themselves as at increased risk
      because they felt different in crucial ways from affected relatives.
      INTERPRETATION: The factors that people and epidemiologists judge as relevant to
      establish presence of a family history can differ. We suggest that these
      differences could lead to misunderstandings between doctor and patient, which
      could undermine advice on CHD risks and associated behavioural changes.

PMID- 11323045
TI  - Orthotopic reimplantation of cryopreserved ovarian cortical strips after high
      dose chemotherapy for Hodgkin's lymphoma.
AB  - BACKGROUND: Infertility is a common late effect of chemotherapy and radiotherapy,
      and has a substantial effect on the quality of life for young survivors of
      cancer. For men, semen cryopreservation is a simple way of preserving
      reproductive potential but for women, storage of mature eggs rarely proves
      successful, and the alternative-immediate in vitro fertilisation with
      cryopreservation of embryos-is not always appropriate. Reimplantation of
      cryopreserved ovarian tissue has been shown to restore natural fertility in
      animals. We applied this technique in a woman who had received sterilising
      chemotherapy for lymphoma. METHODS: A 36-year-old woman underwent a right
      oophorectomy with cryopreservation of ovarian cortical strips before receiving
      high-dose CBV chemotherapy for a third recurrence of Hodgkin's lymphoma. 19
      months later, when serum sex steroid analysis confimed a postmenopausal state,
      two ovarian cortical strips were thawed and reimplanted-one onto the left ovary
      and another at the site of the right ovary. FINDINGS: 7 months after
      reimplantation of ovarian cortical strips, the patient reported resolution of hot
      flashes and, for the first time, oestradiol was detected in the serum. This
      finding was associated with a decrease in the concentrations of follicle
      stimulating hormone and luteinising hormone, and ultrasonography revealed a 10 mm
      thick endometrium, a poorly visualised left ovary, and a 2 cm diameter follicular
      structure to the right of the midline. The patient had one menstrual period, but
      by 9 months after the implantation, her sex steroid concentrations had returned
      to those seen with ovarian failure. INTERPRETATION: Orthotopic reimplantation of
      frozen/thawed ovarian cortical strips is a well tolerated technique for restoring
      ovarian function in women treated with sterilising chemotherapy for cancer.

PMID- 11323046
TI  - A puzzling case of hyperkalaemia.

PMID- 11323047
TI  - Three-dimensional magnetic resonance imaging of fetal brains.
AB  - We assessed ten prenatal magnetic resonance imaging(MRI) scans for fetal brain
      anomalies, and identified eight that were suitable for post-processing.
      Anatomical abnormalities were assessed on three-dimensional (3D) models and
      compared with two-dimensional (2D) imaging. We calculated the volumes of the
      intracranial ventricles and of a periventricular haemorrhage. In three cases,
      additional clinical information was obtained. 3D modelling of the brain in-utero
      is possible and can be used to plan treatment.

PMID- 11323048
TI  - Infections due to vancomycin-resistant Enterococcus faecium resistant to
      linezolid.
AB  - Linezolid is a new oxazolidinone antibiotic used to treat infections caused by
      vancomycin-resistant enterococci (VRE). In early clinical trials, emergence of
      resistance occurred rarely. We report clinical details and antibiotic
      susceptibility from five patients treated with linezolid for VRE infections who
      had resistant organisms isolated during therapy. Four were transplant patients
      receiving protracted courses of the drug; three cases were associated with
      treatment failure. One of 45 linezolid-treated patients developed resistance
      during therapy. Susceptibility testing should be done in all cases on starting
      therapy.

PMID- 11323049
TI  - Ratio of donor kidney weight to recipient bodyweight as an index of graft
      function.
AB  - Reduced renal mass or mismatching kidney size are risk factors for chronic
      allograft nephropathy. We assessed the effect of mismatching donor kidney weight
      and recipient bodyweight on renal graft function in 82 live donor kidney
      transplant recipients who did not have acute rejection. We calculated the donor
      kidney weight to recipient bodyweight ratio, and established the relation between
      this ratio and renal indices with a mixed model regression. We showed that
      recipients with a high ratio had better graft function.

PMID- 11323050
TI  - Germline SDHD mutation in familial phaeochromocytoma.
AB  - The genetic basis for familial phaeochromocytoma is unknown in many cases. Since
      the disorder has been reported in some cases of familial head and neck
      paraganglioma, which is caused by a mutation in the gene encoding succinate
      dehydrogenase complex subunit D (SDHD), we investigated this gene in kindreds
      with familial phaeochromocytoma. A germline SDHD frameshift mutation was
      identified in a two-generation family consisting of four children with
      phaeochromocytoma, but somatic mutations were not detected in 24 sporadic
      phaeochromocytoma tumours. Germline SDHD mutation analysis should be done in
      individuals with familial, multiple, or early-onset phaeochromocytomas even if a
      personal or family history of head and neck paraganglioma is absent.

PMID- 11323051
TI  - Uncertain impact of global warming on disease.

PMID- 11323055
TI  - DAFNE--controlling diabetes the German way.

PMID- 11323056
TI  - New hope for genital herpes treatment.

PMID- 11323058
TI  - Cellular pump changes prospect of disease resistance.

PMID- 11323059
TI  - Retreat on US standards for health, safety, and environment.

PMID- 11323060
TI  - Appeal court bans use of emergency contraceptive in Chile.

PMID- 11323063
TI  - European Parliament proposes to coordinate health policy across Europe.

PMID- 11323064
TI  - Netherlands legalise euthanasia.

PMID- 11323065
TI  - Treating HIV in South Africa--a tale of two systems.

PMID- 11323066
TI  - The CONSORT statement: revised recommendations for improving the quality of
      reports of parallel-group randomised trials.
AB  - To comprehend the results of a randomised controlled trial (RCT), readers must
      understand its design, conduct, analysis, and interpretation. That goal can be
      achieved only through total transparency from authors. Despite several decades of
      educational efforts, the reporting of RCTs needs improvement. Investigators and
      editors developed the original CONSORT (Consolidated Standards of Reporting
      Trials) statement to help authors improve reporting by use of a checklist and
      flow diagram. The revised CONSORT statement presented here incorporates new
      evidence and addresses some criticisms of the original statement. The checklist
      items pertain to the content of the Title, Abstract, Introduction, Methods,
      Results, and Discussion. The revised checklist includes 22 items selected because
      empirical evidence indicates that not reporting this information is associated
      with biased estimates of treatment effect, or because the information is
      essential to judge the reliability or relevance of the findings. We intended the
      flow diagram to depict the passage of participants through an RCT. The revised
      flow diagram depicts information from four stages of a trial (enrollment,
      intervention allocation, follow-up, and analysis). The diagram explicitly shows
      the number of participants, for each intervention group, included in the primary
      data analysis. Inclusion of these numbers allows the reader to judge whether the
      authors have done an intention-to-treat analysis. In sum, the CONSORT statement
      is intended to improve the reporting of an RCT, enabling readers to understand a
      trial's conduct and to assess the validity of its results.

PMID- 11323067
TI  - Rediscovering commotio cordis.

PMID- 11323068
TI  - Brill-Zinsser disease.

PMID- 11323077
TI  - Hypothalamic neuropeptide mechanisms for regulating energy balance: from rodent
      models to human obesity.
AB  - In small rodents there is compelling evidence of a lipostatic system of body mass
      regulation in which peripheral signals of energy storage are decoded in the
      hypothalamus. The ability of small mammals to defend an appropriate mass against
      imposed energy imbalance has implicated hypothalamic neuroendocrine systems in
      body mass regulation. The effect of the neuropeptide systems involved in this
      regulation is primarily compensatory. However, small mammals can also effect
      changes in the level of body mass that they will defend, as exemplified by
      seasonal species. Regulatory control over fat mass may be relatively loose in
      humans; the sizes of long-term storage depots may not themselves be regulated,
      but rather may be a consequence of temporal variations in the matching of supply
      and demand. Whether food intake is regulated to match energy demand, or to match
      demand and to regulate storage, it is clear that physiological defects or genetic
      variation in hypothalamic and peripheral feedback systems will have profound
      implications for fat storage. Study of mechanisms implicated in energy
      homeostasis in laboratory rodents is likely to continue to identify targets for
      pharmacological manipulation in the management of human obesity.

PMID- 11323078
TI  - Corticosteroids in relation to fear, anxiety and psychopathology.
AB  - Corticosteroids play extremely important roles in fear and anxiety. The
      mechanisms by which corticosteroids exert their effects on behavior are often
      indirect, because, although corticosteroids do not regulate behavior, they induce
      chemical changes in particular sets of neurons making certain behavioral outcomes
      more likely in certain contexts as a result of the strengthening or weakening of
      particular neural pathways. The timing of corticosteroid increase (before, during
      or after exposure to a stressor) determines whether and how behavior is affected.
      The present review shows that different aspects of fear and anxiety are affected
      differentially by the occupation of the mineralocorticoid receptor (MR) or
      glucocorticoid receptor (GR) at different phases of the stress response.
      Corticosteroids, at low circulating levels, exert a permissive action via brain
      MRs on the mediation of acute freezing behavior and acute fear-related plus-maze
      behavior. Corticosteroids, at high circulating levels, enhance acquisition,
      conditioning and consolidation of an inescapable stressful experience via GR
      mechanisms. Brain GR-occupation also promotes processes underlying fear
      potentiation. Fear potentiation can be seen as an adjustment in anticipation of
      changing demands. However, such feed-forward regulation may be particularly
      vulnerable to dysfunction. MR and/or GR mechanisms are involved in fear
      extinction. Brain MRs may be involved in the extinction of passive avoidance, and
      GRs may be involved in mediating the extinction of active avoidance. In the
      developing brain, corticosteroids play a facilitatory role in the ontogeny of
      freezing behavior, probably via GRs in the dorsal hippocampus, and their
      influence on the development of the septo-hippocampal cholinergic system.
      Corticosteroids can exert maladaptive rather than adaptive effects when their
      actions via MRs and GRs are chronically unbalanced due to chronic stress. Both
      mental health of humans and animal welfare is likely to be seriously threatened
      after psychosocial stress, prolonged stress, prenatal stress or postnatal stress,
      especially when maternal care or social support is absent, because these can
      chronically dysregulate the central MR/GR balance. In such circumstances the
      normally adaptive corticosteroid responses can become maladaptive.

PMID- 11323079
TI  - KO's and organisation of peptidergic feeding behavior mechanisms.
AB  - Feeding behavior results from complex interactions arising between numerous
      neuromediators, including classical neurotransmitters and neuropeptides present
      in hypothalamic networks. One way to unravel these complex mechanisms is to
      examine animal models with a deletion of genes coding for the different
      neuropeptides involved in the regulation of feeding. The aim of this review is to
      focus on feeding and body weight regulation in mice lacking neuropeptide Y (NPY),
      melanocortins (POMC), corticotropin-releasing hormone, melanin-concentrating
      hormone, or bombesin-like peptides respectively. The phenotypes, which relate to
      the deletion of gene coding for the peptides, rarely include changes in body
      weight and food intake, indicating therefore the existence of redundant
      mechanisms to compensate for the loss of the peptide. The phenotype is much more
      marked when the gene deletion is targeted towards the functioning of the
      peptidergic machinery, e.g. the receptors and especially the POMC and NPY
      receptors, as well as one subtype of bombesin receptor (BRS-3). These knockout
      models are also interesting when examining the role of environmental and social
      factors in the determination of feeding behavior. They have granted us better
      knowledge of all these integrated and complex mechanisms. Moreover, they are also
      valuable tools for pharmacological studies when specific antagonists are lacking.
      From the information obtained by the study of knockouts, it is possible to
      determine certain targets for selective drugs that could be efficient for the
      pharmacological treatment of obesity. However, at the present state of our
      knowledge, it seems necessary to target several peptides in order to get good
      results with weight loss. It will also be imperative to associate these
      multitherapies with changes in eating and behavioral habits, in order to obtain
      complete effectiveness and long-lasting results.

PMID- 11323080
TI  - Complexity of olfactory lateralization processes revealed by functional imaging:
      a review.
AB  - Currently available techniques used in neurosciences and particularly cerebral
      imaging are contributing to a better understanding of human perception and the
      treatment of sensorial information. In this field, the chemical senses (taste and
      smell) have received little attention when compared with the auditory, visual and
      tactile senses. Nevertheless, recent research has been trying to overcome this.
      Brain regions involved in the processing of olfactory information have been
      investigated in several studies including a large number dealing with the
      question of lateralization. However, functional asymmetry in olfaction has still
      not been resolved and the resulting data have not been homogeneous. In this
      field, the contribution of cerebral imaging studies is very important insofar as
      it shows that the processes of functional lateralization in olfaction depend on
      many factors (nature of stimulus, nature of task, characteristics of subjects
      ...) that future research will have to consider.

PMID- 11323081
TI  - Macronutrient-induced cascade of events leading to parallel changes in
      hypothalamic serotonin and insulin.
AB  - Extracellular serotonin (5-HT) and insulin from hypothalamic PVN-VMH region
      follow parallel changes in response to specific macronutrient ingestion. Possible
      independent or causal mechanisms have been investigated. A common primary event
      might be pancreatic insulin secretion for both insulin entry into the brain and 5
      HT synthesis through variations in the ratio of tryptophan over competitor amino
      acids. The steps of this cascade were found to account only partly for the
      changes in hypothalamic 5-HT and insulin. The central consequences of these
      metabolic effects may be modulated directly at the hypothalamic level. For
      instance, we observed a positive relation between the changes in insulin and 5-HT
      and the satiating potency of each nutrient. In addition, a direct action of
      dexfenfluramine on insulin has been found at the hypothalamic level showing that
      an activation of the serotonergic system immediately enhances insulin levels.
      This central event may be an important step in a cascade of events triggered by
      macronutrient ingestion leading to common hypothalamic insulin and 5-HT changes
      involved in feeding regulation.

PMID- 11323082
TI  - Defining the states of consciousness.
AB  - Consciousness remains an elusive concept due to the difficulty to define what has
      been regarded for many years as a subjective experience, therefore irrelevant for
      scientific study. Recent development in this field of research has allowed to
      provide some new insight to a possible way to define consciousness. Going through
      the extensive literature in this domain, several perspectives are proposed to
      define this concept. (1) Consciousness and Attention may not reflect the same
      process. (2) Consciousness during wake and sleep may not involve the same
      mechanisms. (3) Besides physiological states of consciousness, human beings can
      experience modified states of consciousness either by self-training
      (transcendental meditation, hypnosis, etc.) or by drug intake (hallucinogens,
      anaesthetics, etc.). Altogether, we address the question of a more precise
      terminology, given the theoretical weight words can convey. To this respect, we
      propose different definitions for concepts like consciousness, vigilance, arousal
      and alertness as candidates to separate functional entities.

PMID- 11323083
TI  - Could the 5-HT1B receptor inverse agonism affect learning consolidation?
AB  - Diverse evidence indicates that, the 5-HT system might play a role in learning
      and memory, since it occurs in brain areas mediating such processes and 5-HT
      drugs modulate them. Hence in this work, in order to explore further 5-HT
      involvement on learning and memory 5-HT1B receptors' role is investigated.
      Evidence indicates that SB-224289 (a 5-HT1B receptor inverse agonist) post
      training injection facilitated learning consolidation in an associative
      autoshaping learning task, this effect was partially reversed by GR 127935 (a 5
      HT1B/1D receptor antagonist), but unaffected by MDL 100907 (a 5-HT2A receptor
      antagonist) or ketanserin (a 5-HT1D/2A/7 receptor antagonist) at low doses.
      Moreover, SB-224289 antagonized the learning deficit produced by TFMPP (a 5
      HT1A/1B/1D/2A/2C receptor agonist), GR 46611 (a 5-HT1A/1B/1D receptor agonist),
      mCPP (a 5-HT2A/2C/3/7 receptor agonist/antagonist) or GR 127935 (at low dose). SB
      224289 did not alter the 8-OH-DPAT (a 5-HT1A/7 receptor agonist) learning
      facilitatory effect. SB-224289 eliminated the deficit learning produced by the
      anticholinergic muscarinic scopolamine or the glutamatergic antagonist
      dizocilpine. Administration of both, GR 127935 (5mg/kg) plus ketanserin (0.01
      mg/kg) did not modify learning consolidation; nevertheless, when ketanserin dose
      was increased (0.1-1.0mg/kg) and SB-224289 dose was maintained constant, a
      learning facilitation effect was observed. Notably, SB-224289 at 1.0mg/kg
      potentiated a subeffective dose of the 5-HT1B/1D receptor agonist/antagonist
      mixed GR 127935, which facilitated learning consolidation and this effect was
      abolished by ketanserin at a higher dose. Collectively, the data confirm and
      extend the earlier findings with GR 127935 and the effects of non-selective 5
      HT(1B) receptor agonists. Clearly 5-HT1B agonists induced a learning deficit
      which can be reversed with SB-224289. Perhaps more importantly, SB-224289
      enhances learning consolidation when given alone and can reverse the deficits
      induced by both cholinergic and glutamatergic antagonist. Hence, 5-HT1B receptor
      inverse agonists or antagonists could represent drugs for the treatment of
      learning and memory dysfunctions.

PMID- 11323084
TI  - Hepatic insulin expression improves glycemic control in type 1 diabetic rats.
AB  - Low levels of hepatic insulin production have been shown to prevent lethal
      ketoacidosis associated with type 1 diabetes. To assess the beneficial effects of
      sustained hepatic production of insulin on glycemic control in type 1 diabetes,
      we have employed the adenovirus-mediated gene delivery system to transfer an
      engineered rat preproinsulin gene to the livers of streptozotocin-induced
      diabetic nude rats. Hepatic insulin production resulted in the reduction of blood
      glucose in treated diabetic rats, the degree of blood glucose reduction
      correlated with both the vector dose and the level of hepatic insulin expression.
      At moderate vector doses, 0.3-0.7 ng/ml of plasma insulin was produced in treated
      diabetic animals, resulting in significant reduction of nonfasting hyperglycemia
      and improvement in glucose tolerance. Furthermore, these animals maintained
      euglycemia after 12-h fast. At higher vector doses, greater than 1 ng/ml of
      plasma insulin was produced, completely reversing nonfasting hyperglycemia in
      treated rats. However, all of the treated animals developed severe hypoglycemia
      upon fasting. This study has defined the maximal tolerable level of hepatic
      insulin production that is sufficient to reduce the degree and ameliorate the
      adverse effects of nonfasting hyperglycemia without risk of fasting hypoglycemia
      in type 1 diabetic rats.

PMID- 11323085
TI  - Glycine betaine excretion is not directly linked to plasma glucose concentrations
      in hyperglycaemia.
AB  - Diabetes mellitus subjects, type 1 and type 2, have increased glycine betaine
      excretion compared to normal subjects that correlated with plasma glucose and
      HbA(1C) concentrations. The current study was undertaken to determine whether
      elevated glucose concentration directly increases glycine betaine excretion in an
      animal model. Non-pregnant female Coopworth sheep received an intravenous glucose
      load (12.5,25 and 50% w/v; rate 200 ml/h) for 6 h followed by a 12 h
      physiological saline washout (0.9% w/v). Plasma and urine samples were analyzed
      for glycine betaine and glucose. Urine volumes and osmolality were also measured.
      Using the non-parametric Kruskal Wallis analysis of variance test we found no
      difference in glycine betaine excretion between glucose loaded and saline infused
      control animals (P=0.861). However, a significant negative correlation (r=-0.28,
      P<0.001) was observed between urine osmolality and glycine betaine excretion
      independent of treatment. We conclude that acute elevations of plasma glucose
      concentrations did not result in increased glycine betaine excretion and is
      therefore unlikely to be directly responsible for elevated glycine betaine
      excretion observed in diabetes mellitus subjects.

PMID- 11323086
TI  - Mutation screening of the hepatocyte nuclear factor (HNF)-6 gene in Japanese
      subjects with diabetes mellitus.
AB  - Heterozygous mutations in the genes encoding transcription factors (HNF-1alpha,
      HNF-1beta and HNF-4alpha) in the hepatocyte nuclear factor (HNF) network are
      associated with maturity-onset diabetes of the young (MODY). We screened HNF-6
      gene for mutations in 34 Japanese subjects with MODY/early-onset diabetes
      mellitus and 56 subjects with late-onset diabetes mellitus. One single nucleotide
      polymorphism (SNP) at codon 287 (GGG to GGT) was found in the gene and the
      frequency was similar among MODY/early-onset diabetes, late-onset diabetes and
      control subjects. Genetic variations in the HNF-6 gene are not likely to
      contribute to the susceptibility to diabetes mellitus in Japanese.

PMID- 11323087
TI  - Effect of alpha-lipoic acid on the progression of endothelial cell damage and
      albuminuria in patients with diabetes mellitus: an exploratory study.
AB  - Oxidative stress plays a central role in the pathogenesis and progression of late
      microangiopathic complications (diabetic nephropathy) in diabetes mellitus.
      Previous studies suggested that treatment of diabetic patients with the
      antioxidant alpha-lipoic acid reduce oxidative stress and urinary albumin
      excretion. In this prospective, open and non-randomized study, the effect of
      alpha-lipoic acid on the progression of endothelial cell damage and the course of
      diabetic nephropathy, as assessed by measurement of plasma thrombomodulin and
      urinary albumin concentration (UAC), was evaluated in 84 patients with diabetes
      mellitus over 18 months. Forty-nine patients (34 with Type 1 diabetes, 15 with
      Type 2 diabetes) had no antioxidant treatment and served as a control group.
      Thirty-five patients (20 with Type 1 diabetes, 15 with Type 2 diabetes) were
      treated with 600 mg alpha-lipoic acid per day. Only patients with an urinary
      albumin concentration <200 mg/l were included into the study. After 18 months of
      follow up, the plasma thrombomodulin level increased from 35.9+/-9.5 to 39.7+/
      9.9 ng/ml (P<0.05) in the control group. In the alpha-lipoic acid treated group
      the plasma thrombomodulin level decreased from 37.5+/-16.2 to 30.9+/-14.5 ng/ml
      (P<0.01). The UAC increased in patients without alpha-lipoic acid treatment from
      21.2+/-29.5 to 36.9+/-60.6 ng/l (P<0.05), but was unchanged with alpha-lipoic
      acid. It is postulated that the significant decrease in plasma thrombomodulin and
      failure of UAC to increase observed in the alpha-lipoic acid treated group is due
      to antioxidative effects of alpha-lipoic acid, and if so that oxidative stress
      plays a central role in the pathogenesis of diabetic nephropathy. Furthermore,
      progression of the disease might be inhibited by antioxidant drugs. A placebo
      controlled study is needed.

PMID- 11323088
TI  - Heart rate elevation and diabetic retinopathy in patients with type 2 diabetes
      mellitus and normoalbuminuria.
AB  - To investigate the role of heart rate (HR) and blood pressure (BP) for diabetic
      retinopathy, 24-h ambulatory HR and BP were monitored for 162 in patients with
      type 2 diabetes and normoalbuminuria. The fundus was assessed as no retinopathy,
      simple diabetic retinopathy (SDR) and proliferative retinopathy (PDR). Comparing
      the highest with the lowest quartile of diabetic duration, the relative risk for
      retinopathy was 9.3 and for nocturnal HR, it was 3.6. Comparison among three
      retinopathy groups (no retinopathy, group 1, n=122; SDR, group 2, n=24; Pre-PDR
      or PDR, group 3, n=16) showed that 24-h and nocturnal HR were significantly
      higher in group 3 (80+/-9 and 71+/-9 beats per min) than in group 2 (73+/-8 and
      64+/-8) and group 1 (72+/-7 and 60+/-7). In multiple logistic analysis, the odds
      ratio of diabetic duration and nocturnal HR to the existence of retinopathy was
      1.17 (95% CI, 1.10-1.25, P=0.00001) and 1.11 (95% CI, 1.05-1.17, P=0.0002). We
      concluded that diabetic retinopathy is related to diabetic duration and high
      heart rate in type 2 diabetes mellitus with normoalbuminuria. Heart rate
      elevation may be a predictor of advanced retinopathy.

PMID- 11323089
TI  - Safety and efficacy of acarbose in the treatment of Type 2 diabetes: data from a
      5-year surveillance study.
AB  - This 5-year surveillance study assessed the tolerability and safety of acarbose
      in patients with diabetes. A total of 2035 patients were enrolled of whom 1954
      were classified as having Type 2 diabetes. The study was open with no control
      group. Physicians had sole control of the acarbose doses prescribed. Fasting
      blood glucose levels, 2-h postprandial glucose levels, HbA(1) or HbA(1c) and
      other clinical parameters, such as lipids and liver enzyme levels, were also
      assessed as measures of efficacy and safety. One-third of the patients received
      acarbose as monotherapy and two-thirds in combination with other glucose-lowering
      treatment. The concomitant diseases were also assessed. Doses of acarbose were
      low in the majority of the patients and well tolerated. The incidence of acarbose
      associated side effects was 4.7%. No sustained adverse changes in laboratory
      measures occurred. Over the 5 years, HbA(1) and glycated haemoglobin (HbA(1c))
      decreased by 2.4 and 1.8% points, respectively, and the mean fasting glucose and
      2-h postprandial glucose decreased by 2.7 and 3.4 mmol/l. Mean body weight was
      reduced by 0.9 kg. The results suggest that when used in long-term day-to-day
      management of diabetes, acarbose is well tolerated and can improve glycaemic
      control as monotherapy, as well as in combination therapy. In a high-risk patient
      group acarbose proved to be a safe drug.

PMID- 11323090
TI  - Antibodies to diabetes-associated autoantigens in Indian patients with Type 1
      diabetes: prevalence of anti-ICA512/IA2 and anti-SOX13.
AB  - We ascertained frequencies of autoantibodies to a suite of islet cell antigens
      including ICA512/IA2 and SOX13 in Asian Indians with Type 1 diabetes and in other
      forms of diabetes. Autoantibodies to ICA512/IA2 and SOX13 were tested by
      radioimmunoprecipitation assay, and results were amalgamated with previous data
      on antibodies to glutamic acid decarboxylase (GAD) and to islet cell cytoplasmic
      antigens (ICA). The frequency of anti-SOX13 was higher in Asian Indians than in
      Europids. Overall, the combined frequency for all autoantibodies to diabetes
      associated antigens in Type 1 diabetes in Indians approached the frequency
      reported for Europids. There was an unexpectedly high frequency of autoantibody
      reactions to any one of the autoantigens tested (24%) in fibrocalculous
      pancreatic diabetes, however, individual autoantibody frequencies were relatively
      low. Our data indicate that, whatever the population studied, testing for
      multiple autoantigenic reactivities is more informative than more limited
      testing, and that there may be regional (presumably ethnically based) differences
      in levels of particular autoantibodies in cases of Type 1 diabetes.

PMID- 11323091
TI  - Postural sway and diabetic peripheral neuropathy.
AB  - The focus of this paper is to evaluate the relationship between postural sway
      assessed by a gravicorder and peripheral neuropathy in patients with type 2
      diabetes. Posturography (GRAVICHART), electrophysiological tests, and power
      spectrum analysis of heart rate fluctuations were performed in the following age
      matched subjects: 123 type 2 diabetic patients without peripheral neuropathy, 32
      type 2 diabetic patients with peripheral neuropathy, and 55 healthy control
      subjects. All diabetic patients with a history of clinical neurological
      dysfunction were excluded from the study. Significant correlations were found
      between parameters of GRAVICHART and some parameters of the electrophysiological
      tests as well as the parameters of heart rate variability. The envelope area and
      the length per time were larger in type 2 diabetic patients with peripheral
      neuropathy than in patients without peripheral neuropathy and the control
      subjects. There were no significant differences in the GRAVICHART parameters
      between diabetic patients without neuropathy and the healthy control subjects.
      Type 2 diabetic patients with peripheral neuropathy exhibited an inability to
      maintain an upright posture. The GRAVICHART can indicate the early stage of
      postural balance impairment.

PMID- 11323092
TI  - Dose-response study of myo-inositol as an inhibitor of lung tumorigenesis induced
      in A/J mice by benzo.
AB  - Dietary myo-inositol is an effective inhibitor of lung tumor induction in mice,
      but no dose-response studies have been reported. We assessed the ability of
      various doses of dietary myo-inositol to inhibit lung tumor induction in female
      A/J mice treated with eight weekly doses of benzo[a]pyrene (BaP) plus 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) (3 micromol of each by
      gavage), then killed 18 weeks later. In Expt. 1, groups of 20 mice each were
      treated with myo-inositol at concentrations of 1, 0.5, 0.25, 0.125, 0.0625,
      0.03125, and 0% in AIN-93 diet for 1 week prior to, during, and for 1 week after
      the carcinogen administration period. In Expt. 2, groups of 20 mice each were
      treated with the same concentrations of myo-inositol in the diet as in Expt. 1,
      except this diet was administered from 1 week after carcinogen administration
      until termination. There were no effects of myo-inositol on lung tumor incidence,
      which was 100% in all groups treated with BaP plus NNK. However, myo-inositol
      significantly decreased lung tumor multiplicity in both experiments. In Expt. 1,
      significant reductions of 28.9 and 33.0% were observed at the 1 and 0.5% doses of
      myo-inositol, but not at the lower doses. In Expt. 2, a significant reduction of
      48.4% was observed at the 1% dose. In both Expts. 1 and 2, there was a
      significant dose trend for inhibition (P<0.0001). No toxicity was observed at any
      dose. These results firmly establish myo-inositol as a chemopreventive agent
      against lung tumor induction in A/J mice, at doses that can be envisioned for
      human use.

PMID- 11323093
TI  - Benzo(a)pyrene-coated onto Fe(2)O(3) particles-induced lung tissue injury: role
      of free radicals.
AB  - Lipid peroxidation (as malondialdehyde; MDA), activities of some antioxidant
      enzymes (as superoxide dismutase; SOD, glutathione peroxidase; GPx, glutathione
      reductase; GR), glutathione status, and oxidative DNA damage (as 8-hydroxy-2'
      deoxyguanosine; 8-OHdG) were investigated in the lungs of rats exposed to
      hematite (Fe(2)O(3); 3 mg), benzo(a)pyrene (B(a)P; 3 mg), or B(a)P (3 mg)-coated
      onto Fe(2)O(3) particles (3 mg). Approximately 2-fold increases in MDA production
      were seen in animals exposed to Fe(2)O(3), B(a)P, or B(a)P-coated onto Fe(2)O(3)
      particles (P<0.01). Decreases in SOD activities were observed in rats treated
      with Fe(2)O(3) (1.66-fold, P<0.01), B(a)P (1.66-fold, P<0.001) or B(a)P-coated
      onto Fe(2)O(3) particles (1.43-fold, P<0.01). GPx and GR activities could not be
      detected. No alteration of the glutathione status was observed. Significant
      increases in the 8-OHdG formation occurred in response to exposure to B(a)P (2.0
      fold, P<0.01) or B(a)P-coated onto Fe(2)O(3) particles (23.7-fold, P<0.001). Our
      results demonstrate also that Fe(2)O(3) generates free radical (FR)-induced lung
      injury and is not an inert carrier. We established that exposure to B(a)P or
      B(a)P-coated onto Fe(2)O(3) particles resulted in lipid peroxidation and SOD
      inactivation, thereby leading to oxidative damages in DNA. The main findings of
      this work was that B(a)P-coated onto Fe(2)O(3) particles caused higher lung
      concentrations of 8-OHdG than B(a)P by itself. Hence, our data may explain why
      exposure to B(a)P-coated onto Fe(2)O(3) particles resulted in a decreased latency
      and an increased incidence of lung tumors in rodents compared to exposure to
      B(a)P.

PMID- 11323094
TI  - Laserthermia enhances the clastogenic effects of antineoplastic agents in aerobic
      and chronically hypoxic HeLa cells in vitro.
AB  - The interactive clastogenic effects of Nd-YAG laser induced hyperthermia
      (laserthermia) in combination with antineoplastic agents on normally oxygenated
      and chronically hypoxic HeLa cells were investigated. Exponentially growing HeLa
      cells were treated with bleomycin sulfate (BLM) (2-4 microg/ml), adriamycin (ADM)
      (2-4 microg/ml) and actinomycin D (ACT) (0.2-0.4 microg/ml) alone or in
      combination with laser at various powers (7-13 W) or different laser induced
      elevated temperatures (39.5-43.5 degrees C). HeLa cells were incubated with 3
      microg/ml cytochlasin B for 36 h after treatments and the frequency of
      micronuclei (MN) were determined in binucleated cells. Results showed a
      relatively high frequency of MN formation after drug treatments in normally oxic
      and chronically hypoxic cells, although there was a decrease in the frequency of
      MN in hypoxic cells compared to oxygenated cells. Laserthermia at various powers
      and different induced temperatures produced a slight increase in MN formation
      both in oxic and hypoxic cells. When drug treatment and laserthermia was
      combined, a profound synergistic effect in MN formation was observed for all
      three drugs used in these experiments. ACT at a concentration of ten times lower
      than ADM and BLM produced similar effect. Also, ADM showed a marked synergistic
      effect with laserthermia compared to BLM at similar concentrations. This study
      suggests that laserthermia in combination with ADM, BLM or ACT would have a
      greater genotoxic effect on hypoxic cell populations. Therefore, Nd-YAG laser
      induced hyperthermia may be a useful modality for elimination of the
      radioresistant hypoxic cells.

PMID- 11323095
TI  - Co-transfer of human wild-type p53 and granulocyte-macrophage colony-stimulating
      factor genes via recombinant adenovirus induces apoptosis and enhances
      immunogenicity in laryngeal cancer cells.
AB  - Co-transfer of immunomodulatory and anti-proliferative genes may be the basis for
      new strategies to enhance tumor regression. The purpose of this study was to
      develop a combination gene therapy strategy for the treatment of laryngeal
      cancer. Human wild-type p53 and granulocyte-macrophage colony-stimulating factor
      (GM-CSF) genes were transferred into human laryngeal cancer cells mediated by
      adenovirus type 5 vector co-expressing human wild-type p53 and GM-CSF (Ad-p53/GM
      CSF). By the introduction of the wild-type p53 gene, the growth of human
      laryngeal cancer Hep-2 cells was inhibited and their apoptosis was induced. By
      the introduction of the GM-CSF gene, the immunogenicity of cancer cells was
      enhanced. Significant proliferation of tumor infiltrating lymphocytes and tumor
      specific cytotoxicity of cytotoxic T lymphocytes were induced by Ad-p53/GM-CSF
      infected cancer cells in vitro. The results suggest that the co-transfer of human
      wild-type p53 and GM-CSF genes into tumor cells via recombinant adenovirus may be
      further developed into an effective and practical combination gene therapy
      strategy for laryngeal cancer.

PMID- 11323096
TI  - Curcumin, a natural product present in turmeric, decreases tumor growth but does
      not behave as an anticachectic compound in a rat model.
AB  - Systemic administration of curcumin [1,7-bis(4-hydroxy-3-methoxyphenil)1,6
      heptadiene-3,5-dione] (20 microg/kg body weight) for 6 consecutive days to rats
      bearing the highly cachectic Yoshida AH-130 ascites hepatoma resulted in an
      important inhibition of tumor growth (31% of total cell number). Interestingly,
      curcumin was also able to reduce (24%) in vitro tumor cell content at
      concentrations as low as 0.5 microM without promoting any apoptotic events.
      Although systemic administration of curcumin has previously been shown to
      facilitate muscle regeneration, administration of the compound to tumor-bearing
      rats did not result in any changes in muscle wasting, when compared with the non
      treated tumor-bearing animals. Indeed, both the weight and protein content of the
      gastrocnemius muscle significantly decreased as a result of tumor growth and
      curcumin was unable to reverse this tendency. It is concluded that curcumin, in
      spite of having clear antitumoral effects, has little potential as an
      anticachectic drug in the tumor model used in the present study.

PMID- 11323097
TI  - Conservative therapy for adenocarcinoma and atypical endometrial hyperplasia of
      the endometrium in young women: central pathologic review and treatment outcome.
AB  - Thirty-nine patients with endometrioid adenocarcinoma (EA) and atypical
      hyperplasia (AH) of the endometrium who received conservative treatment to
      preserve fertility were collected from member institutions of the Japan
      Gynecologic Oncology Study Group. Twenty-nine and ten were originally diagnosed
      with EA without myometrial invasion and AH, respectively. We performed a central
      pathological review to make definite diagnoses, and the diagnosis of EA in 29
      cases was changed to AH in ten, complex hyperplasia in three and atypical
      polypoid adenomyoma in three, and AH in ten was changed to EA in one and simple
      hyperplasia in one. Nine of 12 women (75%) with EA and 15 of 18 women (83%) with
      AH had an initial response to medroxyprogesterone acetate (MPA) treatment. Two of
      nine responders with EA later developed relapse, and one of them had metastasis
      to the left obturator lymph node. Two became pregnant, and one delivered one full
      term infant. One of the responders with AH had a relapse in the endometrium. Five
      became pregnant, and four delivered four normal infants. The young women with
      endometrial carcinoma localized in the endometrium who wish to preserve fertility
      may be treated as successfully with MPA as those with AH.

PMID- 11323098
TI  - Photodynamic therapy targeted to tumor-induced angiogenic vessels.
AB  - Cancer photodynamic therapy (PDT) with benzoporphyrin derivative monoacid ring A
      (BPD-MA, verteporfin) may be effective not only by being directly cytotoxic to
      tumor cells, but also by being cytotoxic to the endothelium of tumor
      neovasculature. In the present study, we investigated the effect of PDT with an
      experimental liposomal formulation of BPD-MA on tumor-induced angiogenic vessels
      using a murine dorsal air sac model. First, hemostasis of neovasculature was
      examined by varying the regimen of PDT. Laser irradiation at 15 min after
      injection of 2 mg/kg liposomal BPD-MA (15 min PDT) caused complete blocking of
      blood flow in neovasculature. In contrast, PDT did not inhibit blood flow when
      the irradiation occurred 3 h after the injection of liposomal BPD-MA (3 h PDT).
      Next, the antitumor effect of PDT on Meth A sarcoma-bearing mice was investigated
      by using the hemostasis-inducing regimen. Tumor growth was strongly inhibited
      after the 15 min PDT with BPD-MA at a dose of 0.5-2 mg/kg. In contrast, 3 h PDT
      with BPD-MA at a dose of 2 mg/kg suppressed tumor growth only partially. The
      current study indicates that 15 min PDT causes strong suppression of tumor
      growth, perhaps through damaging endothelial cells in the tumor neovasculature
      rather than through a direct cytotoxic effect on tumor cells.

PMID- 11323099
TI  - Postmenopausal obesity as a breast cancer risk factor according to estrogen and
      progesterone receptor status (Japan).
AB  - There have been inconsistent results on the association of postmenopausal obesity
      with breast cancer risk according to the estrogen (ER) and/or progesterone
      receptor (PR) status in the breast tissue, and this requires further evaluation.
      This study was designed to assess whether postmenopausal obesity differs
      according to receptor status. Information on risk factors was obtained from 1154
      breast cancer cases and 21714 controls at Aichi Cancer Center Hospital, Nagoya,
      Japan between 1988 and 1992. The receptor status was known for 40% of cases.
      Obese postmenopausal women showed an increased risk of breast cancer (odds ratio
      (OR) for 5 kg of current weight=1.17, 95% confidence interval (CI)=1.10-1.25; OR
      for 1 kg/m(2) of body mass index (BMI)=1.07, 95% CI=1.04-1.10). The elevated OR
      was strongest for ER-positive, as well as with PR-positive, breast cancer among
      postmenopausal women who had a high BMI. The risk did not differ significantly
      according to ER status. However, obesity indices among postmenopausal women
      differed with borderline significance according to PR status. These results are
      consistent with the hypothesis that there is a gradient of risk for
      postmenopausal obesity according to hormonal receptor status, at least for PR
      status, although this was not statistically significant.

PMID- 11323100
TI  - Expression of p53 protein related to smoking and alcoholic beverage drinking
      habits in patients with esophageal cancers.
AB  - In esophageal squamous cell carcinoma (SCC), we used immunohistochemical analysis
      to further elucidate the correlation of p53 protein expression with
      clinicopathological factors, as well as with risk factors, such as tobacco
      smoking, alcohol consumption and a family history of cancer, using odds ratios
      (ORs). The expression of p53 protein was demonstrated in 55.1% of 89 esophageal
      SCC cases examined by immunohistochemistry. The expression of p53 protein did not
      correlate with gender, age, histological grading, lymph node metastasis, or TNM
      stage. The prevalence of p53 expression was significantly higher in patients with
      multiple primary esophageal cancers (P<0.05). p53 expression did not correlate
      with prognosis in univariate survival analysis. The esophageal SCC in either
      smokers or alcohol users was 4.67-5.83 times more likely to express p53 protein,
      while the likelihood of p53 expression in patients who use both tobacco and
      alcohol was more than 14.0 times. However, a significant association was not
      found between p53 expression and a family history of cancer, this having an OR as
      low as 1.85. The expression of p53 protein did not correlate with
      clinicopathological factors and prognosis in univariate and multivariate survival
      analyses. In contrast, tobacco smoking and alcohol consumption were shown to be
      strongly associated with p53 mutations in esophageal carcinogenesis.

PMID- 11323101
TI  - Significance of MDR1, MRP1, GSTpi and GSTmu mRNA expression in acute
      lymphoblastic leukemia in Indian patients.
AB  - Using, semiquantitative reverse transcription-polymerase chain reaction (RT-PCR)
      in 167 patients of acute lymphoblastic leukemia (ALL) from India at different
      stages of the disease (presentation 125, remission 33, first relapse nine), MRP1
      and GSTpi expression were significantly higher at relapse than presentation
      (P=0.03 and P=0.01, respectively) and remission (P=0.007 and P=0.003,
      respectively). MRP1, GSTpi and GSTmu were expressed simultaneously in several
      samples with significant association of expression levels (P=0.0001). Association
      with clinicopathological features included higher MDR1 expression with age >15
      years (P=0.04) and higher MRP1, GSTpi, GSTmu expression with WBC counts
      >100x10(9)/l. In 71 patients (age <25 years), inability to achieve CR was
      associated with a significantly higher MDR1 mRNA expression (P=0.03) indicating a
      prognostic significance. However, relapse or shorter Event Free Survival was
      independent of mRNA expression levels of the four genes. In view of the increased
      mRNA expression of MRP1/GST at the time of relapse and an association with risk
      factors such as a high WBC count, further studies directed towards investigating
      the functional aspects of GSH/GST/MRP1 mediated drug transport are warranted.

PMID- 11323102
TI  - Differential expression of the subunits of the glucose-6-phosphatase system in
      the clear cell type of human renal cell carcinoma - no evidence for an
      overexpression of protein kinase B.
AB  - The expression of two components of the glucose-6-phosphatase system, the
      catalytic subunit (G6PaseC) and the glucose-6-phosphate transporter, was analyzed
      in the clear cell type of human renal cell carcinoma. The expression of G6PaseC
      was decreased in tumours compared with non-tumourous tissue of the same patient.
      The expression of G6PaseT varied with no general trend between tumours and
      control tissue. The expression of protein kinase B (PKB) was unchanged in the
      tumours, suggesting that the down-regulation of G6PaseC in clear cells and the
      maintenance of the transformed phenotype are not predominantly caused by an
      overexpression of PKB.

PMID- 11323103
TI  - Methylation of the hMLH1, p16, and MDR1 genes in colorectal carcinoma:
      associations with clinicopathological features.
AB  - The methylation status of seven cancer-related genes was investigated in a series
      of 58 colorectal cancers, 18 of which showed the microsatellite instability
      (MSI+) phenotype. Methylation of the hMLH1, p16 and MDR1 genes was found in 23,
      29 and 28% of tumors, respectively. None of the tumors showed methylation of the
      TS, ATM, PARP or p21 genes. Methylation of the hMLH1, p16 and MDR1 genes was more
      frequent and more concordant in MSI+ compared to MSI- tumors (P<0.001) and was
      also strongly associated with poor histological differentiation (P<0.001). There
      were trends for associations between methylation at one or more of these loci and
      proximal tumor location, advanced Dukes' stage and the presence of wild-type p53
      (P=0.06 for each).

PMID- 11323104
TI  - Fatty acid synthase (FAS) expression in human breast cancer cell culture
      supernatants and in breast cancer patients.
AB  - Fatty acid synthase (FAS) is selectively expressed in certain human cancers,
      including carcinoma of the breast, prostate, colon, ovary, and endometrium,
      compared to normal human tissues and therefore is a putative tumor marker. In
      this study, we found FAS concentrations were elevated in cell culture
      supernatants during cell growth in two human breast cancer cell lines but not
      other cancer cell lines. A quantitative enzyme-linked immunosorbent assay and
      Western blot analysis were employed in this study. In addition, serum FAS levels
      were significantly higher in breast cancer patients with different clinical
      stages (Stage II: 0.59+/-0.09 units/l, Stage III: 0.79+/-0.13 units/l, and Stage
      IV: 1.39+/-0.35 units/l) compared with healthy subjects (0.27+/-0.02 units/l,
      P<0.05). Taken together, our data suggest that FAS expression may be a useful
      tumor marker for breast cancer and play a role in assessing cancer virulence.

PMID- 11323105
TI  - HEPES prevents edema in rat brain slices.
AB  - Brain slices gain water when maintained in bicarbonate-buffered artificial
      cerebro-spinal fluid (ACSF) at 35 degrees C. We previously showed that this edema
      is linked to glutamate receptor activation and oxidative stress. An additional
      factor that may contribute to swelling is acidosis, which arises from high CO2
      tension in brain slices. To examine the role of acidosis in slice edema, we added
      N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) to osmotically
      balanced ACSF (HEPES-ACSF), thereby increasing buffering capacity beyond that
      provided by bicarbonate/CO2. Water gain was markedly inhibited in HEPES-ACSF.
      After 3 h incubation in HEPES-ACSF at 35 degrees C, water gain was limited to
      that of fresh slices after 1 h recovery in ACSF at room temperature. The effect
      of HEPES in decreasing slice water gain was concentration dependent from 0.3 to
      20 mM. The inhibition of water gain by HEPES suggests that tissue acidosis is a
      contributing factor in brain slice edema.

PMID- 11323106
TI  - Tryptophan: a precursor for the endogenous synthesis of norharman in man.
AB  - We investigated whether in healthy subjects L-tryptophan may serve as a precursor
      for the endogenous synthesis of the beta-carboline norharman. For this purpose
      subjects, smokers as well as non-smokers, received 0 or 1.2 g of an oral dose of
      tryptophan. Smokers started the experiment 2 h after cessation of smoking. Plasma
      levels of tryptophan and norharman were measured 100 and 125 min after the start
      of the experiment. The levels of both compounds were significantly higher in the
      group receiving tryptophan. Norharman concentrations in the plasma of smokers
      were significantly higher than in the non-smoking subjects under both
      experimental conditions. These results add some proof to the hypothesis that in
      humans tryptophan may serve as a precursor for the synthesis of norharman.

PMID- 11323107
TI  - Production of neuropeptide substance P by synovial fibroblasts from patients with
      rheumatoid arthritis and osteoarthritis.
AB  - We examined the production of substance P (SP) in synovial fibroblasts derived
      from patients with rheumatoid arthritis (RA) and osteoarthritis (OA).
      Immunoreactive SP was observed in non-stimulated RA fibroblasts. The expression
      of beta-preprotachykinin-A (beta-PPT-A) mRNA was confirmed by reverse
      transcription-polymerase chain reaction analysis. SP contents in culture medium
      were increased by treatment of RA fibroblasts with transforming growth factor
      beta (TGFbeta) (10 ng/ml). Levels of SP release were elevated at 12 h after
      TGFbeta stimulation whereas the expression of beta-PPT-A mRNA was enhanced at 3
      h. Furthermore, SP production in response to TGFbeta was dose-dependently
      enhanced by basic fibroblast growth factor (bFGF). OA fibroblasts also
      significantly released SP in the presence of TGFbeta (10 ng/ml) plus bFGF (50
      ng/ml). These results suggest that SP produced by synovial fibroblasts may
      participate in joint diseases.

PMID- 11323108
TI  - Induction of phosphorylated-Stat3 following focal cerebral ischemia in mice.
AB  - It has been shown that Stat3 is induced following transient cerebral ischemia in
      rat. However there is no evidence that cerebral ischemia stimulates the
      expression of phosphorylated-Stat3 (p-Stat3), which can activate cytokine
      mediated signal transduction from the membrane to the nucleus. In the present
      study, we investigated the changes in p-Stat3 expression following middle
      cerebral artery occlusion in mice. Western blot analysis revealed a significant
      increase in the p-Stat3 protein in the peripheral part of the ischemic area,
      starting from 6 h after ischemia. p-Stat3 immunoreactivity was detected only in
      neurons, but not in astrocytes or microglia, and p-Stat3-positive neurons were
      increased in number in the peripheral part of the ischemic area at 24 h after
      ischemia. Double staining with aTdT-mediated biotinylated UTP nick end labeling
      (TUNEL) kit and the p-Stat3 antibody indicated that p-Stat3-positive neurons were
      also TUNEL-positive. Subsequent immuno-electron microscopic observations showed
      that p-Stat3-positive neurons were at different stages of degeneration. The
      present findings suggest that the increased expression of p-Stat3 after cerebral
      ischemia could play a crucial role in ischemia-induced neuron death.

PMID- 11323109
TI  - Different processes are involved in human brain for shape and face comparisons.
AB  - Fifteen subjects participated in a matching task of visual stimuli. Two
      sequentially presented stimuli in a pair were the same shape (shape match),
      different shapes (shape mismatch), same human face (face match) or different
      faces (face mismatch). All four kinds of stimulus pairs were of equal
      probability. The shape mismatch pairs elicited a negative event-related potential
      component N270 (Peak latency: 262.1+/-16.5 ms, P4) after the second stimulus
      onset, while the face mismatch evoked N270 with longer peak latency (301.2+/-19.8
      ms, P4) and N450. There exists a specific system for mismatch processing of a
      complex stimulus (face) in the human brain.

PMID- 11323110
TI  - Circadian rhythm of nitric oxide production in the dorsal region of the
      suprachiasmatic nucleus in rats.
AB  - Extracellular concentration of nitrite (NO2-), an oxidized product of nitric
      oxide (NO), was measured consecutively in the dorsal region of the rat
      suprachiasmatic nucleus (SCN) by means of in vivo microdialysis. The NO2-
      concentrations in the dialysates showed robust circadian rhythm under a 12:12 h
      light/dark cycle and were higher during the dark phase than during the light
      phase. When the rats were transferred to constant darkness, the 24 h rhythm of
      NO2- persisted without damping the amplitude. The NO2- level was significantly
      lowered by an injection of NO synthase inhibitor (NG-monomethyl-L-arginine, 10
      mg/kg i.p.). These findings indicate that the daily fluctuation of NO2- in the
      dorsal region of the SCN, which represents endogenous rhythm of NO, is regulated
      independently of photic inputs into the SCN and may be related to the circadian
      clock functions.

PMID- 11323111
TI  - Striatal dopaminergic metabolism is increased by deep brain stimulation of the
      subthalamic nucleus in 6-hydroxydopamine lesioned rats.
AB  - Deep brain stimulation of the subthalamic nucleus is an established therapeutic
      strategy for patients with Parkinson's disease. Although the exact mechanisms of
      action remain unknown, it is noteworthy that dopaminergic medication can be
      markedly reduced after neurostimulation of the subthalamic nucleus. Previously,
      we have shown that deep brain stimulation of the subthalamic nucleus is followed
      by an increase of striatal extracellular dopamine metabolites in naive rats. In
      the present study we examined the effects of deep brain stimulation on striatal
      monoamine metabolism in the intrastriatal 6-hydroxydopamine rat model of
      Parkinson's disease. Deep brain stimulation of the subthalamic nucleus was
      followed by a delayed increase of extracellular 3,4-dihydroxyphenylacetic and
      homovanillic whereas dopamine levels were unchanged in stimulated rats and
      controls. Our results indicate that deep brain stimulation of the subthalamic
      nucleus affects significantly striatal dopaminergic metabolism in 6
      hydroxydopamine lesioned rats.

PMID- 11323112
TI  - 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin induces apoptosis in the dorsal midbrain
      of zebrafish embryos by activation of arylhydrocarbon receptor.
AB  - Neurotoxic effects of 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) has not been
      fully elucidated, despite the known potent agonist of arylhydrocarbon receptor
      (AhR), which activation induces cytochrome P450 1A and several representative
      toxicities of halogenated aromatic hydrocarbons. In the present study, the
      effects of TCDD on cell death in zebrafish embryos (Danio rerio) during the early
      stage of development were investigated. As shown by terminal transferase-mediated
      nick-end-labeling staining, TCDD exposure significantly increased the occurrence
      of pycnotic cell death (PCD), especially in the dorsal midbrain (optic tectum).
      The ultrastructures of these pycnotic cells showed apoptotic features such as
      condensation and cleavage of chromatin. TCDD-induced PCD was mimicked by beta
      naphthoflavone (AhR agonist), and inhibited by alpha-naphthoflavone (AhR
      antagonist). These results suggest that AhR activation can induce apoptosis in
      the central nervous system during development.

PMID- 11323113
TI  - Effects of nociceptinNH2 and [Nphe1]nociceptin(1-13)NH2 on rat brain
      noradrenaline release in vivo and in vitro.
AB  - We have investigated the effects of nociceptin/orphanin FQ (NC) receptor agonist
      NCNH2 and a competitive NC receptor antagonist, [Nphe1]NC(1-13)NH2 on
      noradrenaline (NA) release in vivo using microdialysis in freely moving animals
      and in vitro from cerebrocortical slices. One nmol of NCNH2 injected into rat
      locus coeruleus inhibited NA release from the prefrontal cortex (E(max) 27.4+/
      5.7% 30 min after injection) which was partially (33%) reversed by 100 nmol of
      [Nphe1]NC(1-13)NH2. In cerebrocortical slices NCNH2 inhibited NA release in a
      concentration-dependent manner (EC50 12 nM, E(max) 29.4%) that was reversed by
      [Nphe1]NC(1-13)NH2. In both preparations, [Nphe1]NC(1-13)NH2 per se was inactive.
      These data demonstrate an inhibition of NA release by NCNH2 in a [Nphe1]NC(1
      13)NH2 sensitive manner in both in vivo brain microdialysis and in vitro
      cerebrocortical slices studies in rats.

PMID- 11323114
TI  - Cortical spreading depression during streptozotocin-induced hyperglycaemia in
      nutritionally normal and early-malnourished rats.
AB  - Cortical spreading depression (SD) was investigated in adult rats during
      Streptozotocin (STZ)-induced hyperglycaemia (group S; n=13). SD velocities of
      propagation were significantly lower than in the controls injected only with
      vehicle solution (group V; n=17). In contrast, rats rendered hypoglycaemic by
      food restriction+insulin for 3 days (group HG; n=9) presented SD velocities
      significantly higher than controls; this effect was reversed by injecting glucose
      during the recording session. SD velocity in early-malnourished rats was not
      different during STZ-hyperglycaemia (group MS; n=8) compared with previously
      malnourished rats injected with vehicle (group MV; n=9). The data indicate an
      inverse relationship between glycaemia changes and SD propagation in well
      nourished rats. Early malnutrition seems to abolish the effect of STZ
      hyperglycaemia on SD.

PMID- 11323115
TI  - Haptoglobin gene expression in human glioblastoma cell lines.
AB  - Increases in cerebrospinal fluid (CSF) levels of the acute phase protein
      haptoglobin (Hp) occur in central nervous system (CNS) disorders such as
      Alzheimer's disease. To establish if Hp CSF level increases can be associated
      with Hp expression in brain, reverse transcription-polymerase chain reaction (RT
      PCR) experiments were conducted to determine if the Hp mRNA transcript is
      expressed in human glioblastoma cells. Furthermore, Western blots and
      immunoprecipitations were performed to elucidate if Hp protein is synthesized and
      secreted by human glioblastoma cells. The Hp mRNA (alpha2beta) transcript (1155
      bp) was detected both in U-87MG and U-138MG cells, and was positively verified by
      nested PCR in which a part of the beta sequence (482 bp) was targeted for
      amplification. Despite the presence of Hp mRNA, Hp protein was not secreted by U
      87MG cells as compared to the hepatoma cell line, HepG2, where Hp protein
      (approximately 46 kDa) was detected in the media. The results suggest the
      expression of Hp protein by glioblastoma cells is possible since the Hp mRNA
      transcript exist, but whether or not Hp mRNA is contained in a storage pool
      requiring a specific signal for translation or is transiently expressed remains
      to be uncovered in future studies.

PMID- 11323116
TI  - Amyloid beta(1-42) and its beta(25-35) fragment induce in vitro
      phosphatidylcholine hydrolysis in bovine retina capillary pericytes.
AB  - We describe the inhibitory effect of full-length Abeta(1-42) and Abeta(25-35)
      fragment of amyloid-beta peptide on phosphatidylcholine (PtdCho) metabolism in
      bovine retina capillary pericytes. Cell cultures were incubated with Abetas for
      24 h. Peroxidation indices (malondialdehyde and lactate dehydrogenase release)
      significantly increased after 20-50 microM Abeta(1-42) or Abeta(25-35) treatment.
      In addition, [Me-3H]choline incorporation into PtdCho strongly decreased while
      either 3H-choline or 14C-arachidonic acid release from prelabeled cells
      increased, indicating PtdCho hydrolysis. The effect was very likely due to
      prooxidant action of both Abeta peptides. Reversed-sequence Abeta(35-25) peptide
      did not depress 3H-choline incorporation nor stimulate PtdCho breakdown. With
      addition of Abetas at low concentrations (2-20 microM) to pericytes, marked
      ultrastructural changes, well connected to metabolic alterations, emerged
      including shrinkage of cell bodies, retraction of processes, disruption of the
      intracellular actin network. Cells treated with higher concentrations (50-200
      microM) displayed characteristics of necrotic cell death. The data suggest that:
      (a) Abeta(1-42) and Abeta(25-35) peptides may modulate phospholipid turnover in
      microvessel pericytes; (b) together with endothelial cells, pericytes could be
      the target of vascular damage during processes involving amyloid accumulation.

PMID- 11323117
TI  - Expression of p-glycoprotein is associated with that of multidrug resistance
      protein 1 (MRP1) in the vestibular labyrinth and endolymphatic sac of the guinea
      pig.
AB  - Expression of p-glycoprotein (p-gp) and multidrug resistance protein 1 (MRP1) was
      detected in the vestibular labyrinth and endolymphatic sac (ES) of the guinea pig
      by immunohistochemical staining using anti-p-gp monoclonal antibody (mAb) C219
      and anti-MRP mAb MRPr1. P-gp was detected in capillary endothelial cells of the
      crista ampullaris, utricle, saccule and ES. MRP1 was detected in the epithelial
      lining of the crista ampullaris, utricle, saccule, and epithelial cells of the
      ES. Since p-gp and MRP1 act as extrusion pumps, they may coordinate with each
      other in vestibular organs and ES and play an important role in the blood
      labyrinth barrier.

PMID- 11323118
TI  - Tau, beta-amyloid and beta-amyloid precursor protein distribution in the
      entorhinal-hippocampal alvear and perforant pathways in the Alzheimer's brain.
AB  - It has been suggested that the pathological lesions of Alzheimer's disease (AD)
      spread along neuronal connections. This study was designed to examine this
      hypothesis in the alvear and perforant pathways, two well-defined neuroanatomical
      pathways that project from the entorhinal cortex to the hippocampus. Paraffin
      sections of hippocampal-entorhinal cortex from 25 AD cases were immunolabelled
      for tau, beta-amyloid (Abeta) and beta-amyloid precursor protein (betaAPP). We
      used image-analysis to quantify immunolabelling at both ends of the alvear and
      perforant pathways. At the beginning and the end of the alvear pathway, area of
      immunolabelling in microm2 per area of field (72000 microm2) were as follows: tau
      349 and 821 (P<0.01), Abeta 349 and 61 (P<0.05) and betaAPP 18 and 73 (P<0.01).
      Corresponding values for the perforant pathway were tau 421 and 387, Abeta 382
      and 115 (P<0.05) and betaAPP 55 and 83. Tau was significantly greater at the end
      than at the beginning of the alvear pathway, but similar at both ends of the
      perforant pathway. There was significantly more Abeta at the beginning than at
      the end of the alvear and perforant pathway. These results at least in part
      reinforce previous work [19] that tau-rich areas may be neuronally connected to
      Abeta-rich areas.

PMID- 11323119
TI  - Alpha-tocopherol controls cell proliferation in the adult rat dentate gyrus.
AB  - The effect of alpha-tocopherol on cell proliferation and proliferated cell
      survival was investigated in the dentate gyrus of adult rats. Adult rats were
      supplemented with alpha-tocopherol, injected with 5-bromo-2'-deoxyuridine (BrdU),
      that is incorporated into DNA during the S-phase, and killed at different time
      after BrdU injection. The number of newborn cells decreased after alpha
      tocopherol supplementation, confirming the hypothesis that alpha-tocopherol is
      able to depress cell proliferation in vivo. Most newborn cells die within few
      days; more newborn cells survive in alpha-tocopherol-treated rats, suggesting the
      hypothesis that alpha-tocopherol decreases cell death.

PMID- 11323120
TI  - Chest pain: cause and consequence of coronary artery bypass grafting?

PMID- 11323121
TI  - Mechanisms of opioid-induced pain and antinociceptive tolerance: descending
      facilitation and spinal dynorphin.

PMID- 11323122
TI  - Prevalence and characteristics of post coronary artery bypass graft surgery pain
      (PCP).
AB  - Coronary artery bypass grafting (CABG) is one of the most common surgical
      procedures performed worldwide. However, its frequent complication, the post-CABG
      pain (PCP) syndrome, remains poorly documented. This retrospective cohort study
      was aimed to investigate the prevalence and characteristics of this syndrome.
      Five hundred and four of 540 subjects, who underwent CABG surgery at our
      institution between January 1995 and December 1996 and who could be identified,
      were mailed questionnaires regarding the presence and characteristics of chest
      wall pain. Eighty of 217 patients, who were defined as having PCP based on these
      questionnaires, were evaluated in detail. Main outcome measures included a
      preliminary pain questionnaire, pain localization on a body scheme, a five-point
      verbal scale and the Visual Analogue Scale (VAS) for measuring pain intensity.
      Pain qualities, disability and depression were measured by the McGill Pain
      Questionnaire (MPQ), the Pain Disability Index (PDI), and the Beck Depression
      Inventory (BDI), respectively. Medical and neurological examinations were also
      conducted, as well as quantitative thermal testing (QTT) of the chest wall. The
      preliminary pain questionnaires indicated that 219 of the 387 respondents (56%)
      reported chest wall pain, which was categorized as PCP. One hundred and forty-two
      (65%) of the patients with PCP reported pain of at least moderate severity, and
      151 (72%) reported that the pain interfered with their daily activities. Eighty
      PCP patients were available for a detailed evaluation. Left-sided chest wall pain
      was noted by 53 subjects, midline scar pain by 47, and right-sided pain by nine
      subjects. Pain intensity (VAS) was 35 +/- 22 (mean +/- SD), MPQ score was 4.9 +/-
      3.7, PDI score was 2.0 +/- 0.7, and BDI score was 9.3 +/- 7.3. The neurological
      examination and the QTT indicated three subcategories of PCP: (1) left-sided
      chest wall pain often associated with hypoesthesia, mechanical allodynia, and
      elevated thermal thresholds; (2) midline scar pain accompanied primarily by
      mechanical allodynia; (3) right-sided, relatively infrequent pain. While the
      first two subcategories seem to have a neurogenic etiology, this later
      subcategory of pain is of a mal-defined etiology. This study indicates that PCP
      is a group of pain syndromes with a high prevalence, and with a negative effect
      on mood and performance of daily activities. The risk of developing PCP and its
      potential consequences should therefore be discussed with every patient prior to
      CABG surgery. These results will need to be confirmed in larger, multi-center
      studies.

PMID- 11323123
TI  - Vagal afferent signaling of a gastric mucosal acid insult to medullary, pontine,
      thalamic, hypothalamic and limbic, but not cortical, nuclei of the rat brain.
AB  - Although gastric acid is a factor in upper abdominal pain, the signaling and
      processing of a gastric mucosal acid insult within the brain are not known. This
      study examined which nuclei in the rat brain respond to challenge of the gastric
      mucosa by a noxious concentration of hydrochloric acid (HCl) and whether the
      central input is carried by vagal afferent neurons. Activation of neurons in the
      brain was mapped by in situ hybridization autoradiography of messenger
      ribonucleic acid (mRNA) for the immediate early gene c-fos 45 min after
      intragastric administration of saline or HCl. Following intragastric HCl (0.5 M)
      challenge, many neurons in the nucleus tractus solitarii, lateral parabrachial
      nucleus, thalamic and hypothalamic paraventricular nucleus, supraoptic nucleus,
      central amygdala and medial/lateral habenula expressed c-fos mRNA as compared to
      intragastric treatment with saline (0.15 M). However, c-fos transcription in the
      insular cortex was not enhanced by the gastric acid insult. Hypertonic saline
      (0.5 M) caused only a minor expression of c-fos mRNA in the hypothalamus and
      amygdala. The acid-evoked c-fos induction in subcortical nuclei was depressed by
      at least 80% five days after bilateral subdiaphragmatic vagotomy. Collectively,
      these observations indicate that vagal afferent input from the acid-threatened
      gastric mucosa does not reach the insular cortex but leads to activation of
      subcortical brain nuclei that are involved in emotional, behavioral,
      neuroendocrine, autonomic and antinociceptive reactions to a noxious stimulus.

PMID- 11323124
TI  - Increased expression of gamma-aminobutyric acid transporters GAT-1 and GAT-3 in
      the spinal trigeminal nucleus after facial carrageenan injections.
AB  - The present study aimed to elucidate the distribution of gamma-aminobutyric acid
      (GABA) transporters in the spinal trigeminal nucleus after carrageenan
      injections. Dense GAT-1 and GAT-3 but very little GAT-2 immunoreactivity was
      observed in the normal rat spinal trigeminal nucleus. The GAT-1-positive glial
      cells in the normal rat spinal trigeminal nucleus contained dense bundles of
      glial filaments and had features of astrocytes. Some GAT-3-positive cells
      contained dense bundles of glial filaments and had features of astrocytes, whilst
      others lacked glial filaments, and contained dense marginated heterochromatin,
      and had features of oligodendrocyte precursor cells. An increase in
      immunoreactivity to both transporters was observed on the injected but not the
      contralateral side 3 days after facial carrageenan injections. In rats given
      three further weekly injections of carrageenan and killed 3 days after the fourth
      injection, further increases in GAT-1 and GAT-3 immunoreactivities were observed.
      Electron microscopy showed that transporter immunoreactivity in the spinal
      trigeminal nucleus of carrageenan-injected rats was predominantly present in
      glial processes, showing that the increase in the number of processes observed at
      light microscopy was due to increased immunoreactivity in glial processes. An
      increased expression of GABA transporters in the carrageenan-injected spinal
      trigeminal nucleus could therefore result in a faster removal of GABA from the
      synaptic cleft of GABAergic axon terminals compared to normal rats. This could
      result in reduced inhibition/increased activity of the trigeminothalamic neurons
      in the spinal trigeminal nucleus, and could contribute to hyperalgesia after
      carrageenan injections.

PMID- 11323125
TI  - The roles of beliefs, catastrophizing, and coping in the functioning of patients
      with temporomandibular disorders.
AB  - Pain-related beliefs, catastrophizing, and coping have been shown to be
      associated with measures of physical and psychosocial functioning among patients
      with chronic musculoskeletal and rheumatologic pain. However, little is known
      about the relative importance of these process variables in the functioning of
      patients with temporomandibular disorders (TMD). To address this gap in the
      literature, self-report measures of pain, beliefs, catastrophizing, coping, pain
      related activity interference, jaw activity limitations, and depression, as well
      as an objective measure of jaw opening impairment, were obtained from 118
      patients at a TMD specialty clinic. Controlling for age, gender, and pain
      intensity, significant associations were found between (1) pain beliefs and
      activity interference, depression, and non-masticatory jaw activity limitations,
      (2) catastrophizing and activity interference, depression, and non-masticatory
      jaw activity limitations, and (3) coping and activity interference and
      depression. Controlling for age, gender, pain intensity, and the other process
      variables, significant associations were found between (1) beliefs and activity
      interference and depression, and (2) catastrophizing and depression. No process
      variable was associated significantly with the objective measure of jaw
      impairment. The results suggest that for patients with moderate or high levels of
      TMD pain and dysfunction, beliefs about pain play an important role in physical
      and psychosocial functioning.

PMID- 11323126
TI  - The behavioural importance of dynamically activated descending inhibition from
      the nucleus reticularis gigantocellularis pars alpha.
AB  - We have recently demonstrated (J Physiol 506 (1998) 459) that the dynamic
      activation of descending inhibition of the nociceptive response of spinal
      multireceptive cells occurs in the nucleus reticularis gigantocellularis pars
      alpha (GiA). In the same paper we have shown that Lamina I dorsal horn cells are
      responsible for activating this inhibition via a pathway which runs in the
      contralateral dorsolateral funiculus. The effects of dynamically activating this
      system by noxious stimulation on behavioural responses to noxious stimuli have
      not been established. Here we demonstrate the effects of GiA on the behavioural
      response during application of standardized noxious stimuli. As this system is
      activated in response to noxious stimulation (J Physiol 506 (1998) 459), it is
      possible that chronic pain states may also activate GiA. We have therefore
      investigated this possibility in animals following partial sciatic nerve ligation
      (an animal model of chronic pain; Pain 43 (1990) 205). Male Wistar rats (280-310
      g) were anaesthetized with halothane (0.5-2% in O(2)). Guide cannulae for
      microinjections were stereotaxically placed above GiA. In one group of animals
      the sciatic nerve was partially ligated. Animals were allowed to recover for 4-6
      days. The responses of each animal during the formalin test (Pain 4 (1977) 161)
      and the tail flick test (Pain 12 (1982) 229) were recorded on different days.
      Microinjections (0.5 microl) of either gamma-aminobutyric acid (GABA, 200 mM), D
      L homocysteic acid (DLH, 25 mM) or 0.9% saline (as control) into GiA were
      performed during these tests in a randomized, blind manner. In animals without
      sciatic nerve ligation, microinjection of GABA to GiA did not significantly
      affect the animal's response during the tail flick test. However microinjection
      of DLH significantly increased the latency of tail flick from 6.2 +/- 0.8 to 8.4
      +/- 0.5 s for up to 15 min (n = 7, P < 0.01, Mann-Whitney U-test). Microinjection
      of GABA to GiA increased the behavioural response to formalin between 10 and 20
      min post-injection, while microinjection of DLH reduced this response at all time
      points except 10 min post-injection (n = 8, P < 0.05, Mann-Whitney U-test). In
      animals with sciatic nerve ligation, microinjections (0.5 microl) of either GABA
      (200 mM), or saline (as control) into GiA contralateral to the partial sciatic
      ligation were performed during these tests in a randomized, blind manner. Partial
      sciatic ligation significantly reduced the behavioural response to
      contralaterally applied formalin from 15 min post-injection onwards, compared to
      controls without sciatic nerve ligation. Microinjection of GABA to GiA
      significantly increased the behavioural response to formalin from 20 to 50 min
      post-injection. The inactivation of GiA only causes behavioural effects in
      nociceptive tests of a long enough duration to activate the system (i.e. the
      formalin test but not the tail flick test). Chemical activation of the system
      affects both tests. These data strongly support the concept of an important
      analgesic system which is activated in response to noxious stimulation, and
      subsequently acts to reduce behavioural responses to noxious stimuli.

PMID- 11323127
TI  - Effects of tramadol on T lymphocyte proliferation and natural killer cell
      activity in rats with sciatic constriction injury.
AB  - We investigated the effects of acute and chronic tramadol treatment on T
      lymphocyte function and natural killer (NK) cell activity in rats receiving
      chronic constriction injury (CCI) of the sciatic nerve. T lymphocyte function was
      evaluated based on concanavalin-A (ConA)- and phytohemagglutinin (PHA)-induced
      splenocyte proliferation. NK cell activity was measured by lactic acid
      dehydrogenase release assay. The effects of tramadol on thermal hyperalgesia were
      also assessed by measuring paw withdrawal latency (PWL) in the rats. PWL was dose
      dependently reversed by tramadol after acute treatment (single subcutaneous
      injection) with 10, 20, and 30 mg/kg, respectively. There was no significant
      change among acute treatment groups in NK cell activity, whereas splenocyte
      proliferation induced by ConA and PHA was significantly suppressed starting from
      a dose of 20 mg/kg. The reversal of the thermal hyperalgesia persisted throughout
      a period of chronic tramadol treatment of 40 and 80 mg/kg per day, respectively,
      with continuous subcutaneous infusion for 7 days at a uniform rate via osmotic
      minipumps. No modulation of NK cell activity was found in either dose group.
      However, the activity of splenocyte proliferation was decreased in the 80 mg/kg
      per day group when compared with the saline and 40 mg/kg per day groups. These
      data suggest that tramadol treatment has an immunological profile different from
      pure mu-opioid agonists like morphine, which is known to suppress both NK cell
      activity and T lymphocyte proliferation at a subanalgesic dose in CCI rats.
      Considering analgesic and immunosuppressive effects, tramadol treatment may be a
      better choice than morphine for treatment of chronic neuropathic pain,
      particularly in patients with compromised immunity.

PMID- 11323128
TI  - Obtaining informed consent for clinical pain research: patients' concerns and
      information needs.
AB  - Investigators who conduct clinical pain research are required to obtain voluntary
      informed consent from patients. However, little is known about what information
      patients expect when they decide whether to enroll in such studies. It is
      important that investigators understand these information needs so they can
      effectively and clearly describe the research risks and potential benefits that
      matter to potential subjects. By understanding these needs for information,
      investigators may also be better able to anticipate patients' concerns and to
      recruit subjects more efficiently. This study was designed to define information
      needs that patients have when they decide whether to participate in clinical pain
      research. This paper describes these information needs, and identifies clinical
      and demographic variables associated with specific needs.

PMID- 11323129
TI  - Orexin-A, an hypothalamic peptide with analgesic properties.
AB  - The hypothalamic peptide orexin-A and the orexin-1 receptor are localized in
      areas of the brain and spinal cord associated with nociceptive processing. In the
      present study, localization was confirmed in the spinal cord and demonstrated in
      the dorsal root ganglion for both orexin-A and the orexin-1 receptor. The link
      with nociception was extended when orexin-A was shown to be analgesic when given
      i.v. but not s.c. in mouse and rat models of nociception and hyperalgesia. The
      efficacy of orexin-A was similar to that of morphine in the 50 degrees C hotplate
      test and the carrageenan-induced thermal hyperalgesia test. However, involvement
      of the opiate system in these effects was ruled out as they were blocked by the
      orexin-1 receptor antagonist SB-334867 but not naloxone. Orexin-1 receptor
      antagonists had no effect in acute nociceptive tests but under particular
      inflammatory conditions were pro-hyperalgesic, suggesting a tonic inhibitory
      orexin drive in these circumstances. These data demonstrate that the orexinergic
      system has a potential role in the modulation of nociceptive transmission.

PMID- 11323130
TI  - The role of central and peripheral Cannabinoid1 receptors in the antihyperalgesic
      activity of cannabinoids in a model of neuropathic pain.
AB  - We have examined the effects of cannabinoid agonists on hyperalgesia in a model
      of neuropathic pain in the rat and investigated the possible sites of action. The
      antihyperalgesic activity of the cannabinoids was compared with their ability to
      elicit behavioural effects characteristic of central cannabinoid activity.
      WIN55,212-2 (0.3-10 mg kg(-1)), CP-55,940 (0.03-1 mg kg(-1)) and HU-210 (0.001
      0.03 mg kg(-1)) were all active in a 'tetrad' of tests consisting of tail-flick,
      catalepsy, rotarod and hypothermia following subcutaneous administration, with a
      rank order of potency in each of HU-210 > CP-55,940 > WIN55,212-2. The effects of
      WIN55,212-2 in each assay were blocked by the Cannabinoid1 (CB1) antagonist
      SR141716A. In the partial sciatic ligation model of neuropathic pain WIN55,212-2,
      CP-55,940 and HU-210 produced complete reversal of mechanical hyperalgesia within
      3 h of subcutaneous administration with D50 values of 0.52, 0.08 and 0.005 mg kg(
      1), respectively. In this model WIN55,212-2 was also effective against thermal
      hyperalgesia and mechanical allodynia. WIN55,212-2 produced pronounced reversal
      of mechanical hyperalgesia following intrathecal administration that was blocked
      by the CB1 antagonist SR141716A. Following intraplantar administration into the
      ipsilateral hindpaw, WIN55,212-2 produced up to 70% reversal of mechanical
      hyperalgesia, although activity was also observed at high doses following
      injection into the contralateral paw. The antihyperalgesic effect of WIN55,212-2
      injected into the ipsilateral paw was blocked by subcutaneously administered
      SR141716A, but was not affected by intrathecally administered SR141716A. These
      data show that cannabinoids are highly potent and efficacious antihyperalgesic
      agents in a model of neuropathic pain. This activity is likely to be mediated via
      an action in both the CNS and in the periphery.

PMID- 11323131
TI  - An in vivo rat model to study calcitonin gene related peptide release following
      activation of the trigeminal vascular system.
AB  - Calcitonin gene related peptide (CGRP) released from the C-fibers projecting from
      the trigeminal ganglion to the meninges has been suggested to play a crucial role
      in the pathophysiology of headache, particularly migraine. In humans it has been
      shown that CGRP is released during migraine-attacks, and this is attenuated by
      the administration of typical anti-migraine drugs such as dihydroergotamine or
      sumatriptan. We describe a new rat model which allows the study of CGRP release
      from the meninges into venous blood following activation of the trigeminal
      vascular system. The effects of classical and new anti-migraine drugs such as
      acetylsalicylic acid (ASA), sumatriptan and the new high efficacy 5-HT1B/1D
      agonist donitriptan (4-[4-[2-(2-aminoethyl)-1H-indol-5-yloxyl]acetyl]piperazinyl
      1-yl]benzonitrile) were evaluated in comparison with the established model of
      neurogenic inflammation in the meninges. Sumatriptan and donitriptan inhibited
      CGRP release as well as neurogenic inflammation. ASA, however, attenuated
      neurogenic inflammation, but not CGRP release, confirming the concept of
      prejunctional inhibition of CGRP release by 5-HT1B/1D receptors. This new model
      allows the further study of prejunctional pharmacology and mechanisms of
      neuropeptide release in the trigeminal vascular system, which might be crucial
      for the further development of potent, more effective anti-migraine drugs.

PMID- 11323132
TI  - Characterization of nociceptive responses and spinal releases of nitric oxide
      metabolites and glutamate evoked by different concentrations of formalin in rats.
AB  - A comparison was made of spontaneous nociceptive behaviors elicited by
      subcutaneous injection of formalin (0.5-10.0%) into the plantar or dorsal surface
      of the right hindpaw in rats. In the present study, we also examined the effect
      of paw formalin injection on the release of nitric oxide (NO) metabolites
      (nitrite/nitrate) and glutamate from the spinal cord in anesthetized rats using a
      dialysis probe placed in the lumbar subarachnoid space. Two distinct quantifiable
      behaviors indicative of pain were identified by formalin injected into both
      regions of the paw. There were no significant alterations in the number of
      flinches during the early and late phases induced by different regions of
      formalin injection. However, the early phase licking/biting activity evoked by
      formalin injection into the plantar surface of the paw was significantly higher
      than that evoked by formalin injected into the dorsal region. The maximum effect
      in the early and late phases was produced by 5.0% formalin injection into the
      dorsal and plantar paw. At a higher concentration (10.0%) of formalin,
      nociceptive behavioral responses were decreased except for the late phase
      flinching when injected into the dorsal paw. Injections of formalin (5.0%) into
      both regions of the paw evoked a biphasic spinal release of nitrite/nitrate with
      a significant increase during the early phase (0-10 min) and the late phase (30
      80 or 90 min). A higher concentration of formalin (10.0%) failed to produce a
      clear-cut release of nitrite/nitrate. A significant increase of glutamate was
      observed in the 0-10 min samples obtained after injection of formalin (5.0%) into
      the plantar and dorsal surface of the paw, whereas 0.5 and 10.0% formalin induced
      no substantial release. These results suggest that 5.0% formalin should be used
      when studying antinociceptive activity of NO- and N-methyl-D-aspartate-related
      compounds in the formalin test in rats. Formalin injection into the plantar
      surface of the paw might prove to be useful for evoking the licking/biting
      response, particularly in the early phase.

PMID- 11323133
TI  - Modulation of jaw muscle spindle afferent activity following intramuscular
      injections with hypertonic saline.
AB  - Transient noxious chemical stimulation of small diameter muscle afferents
      modulates jaw movement-related responses of caudal brainstem neurons. While it is
      likely that the effect is mediated from the spindle afferents in the
      mesencephalic nucleus (Vmes) via the caudally projecting Probst's tract, the
      mechanisms of pain induced modulations of jaw muscle spindle afferents is not
      known. In the present study, we tested the hypothesis that jaw muscle nociceptors
      gain access to muscle spindle afferents in the same muscle via central mechanisms
      and alter their sensitivity. Thirty-five neurons recorded from the Vmes were
      characterized as muscle spindle afferents based on their responses to passive jaw
      movements, muscle palpation, and electrical stimulation of the masseter nerve.
      Each cell was tested by injecting a small volume (250 microl) of either 5%
      hypertonic and/or isotonic saline into the receptor-bearing muscle. Twenty-nine
      units were tested with 5% hypertonic saline, of which 79% (23/29) showed
      significant modulation of mean firing rates (MFRs) during one or more phases of
      ramp-and-hold movements. Among the muscle spindle primary-like units (n = 12),
      MFRs of 4 units were facilitated, five reduced, two showed mixed responses and
      one unchanged. In secondary-like units (n = 17), MFRs of 9 were facilitated,
      three reduced and five unchanged. Thirteen units were tested with isotonic
      saline, of which 77% showed no significant changes of MFRs. Further analysis
      revealed that the hypertonic saline not only affected the overall output of
      muscle spindle afferents, but also increased the variability of firing and
      altered the relationship between afferent signal and muscle length. These results
      demonstrated that activation of muscle nociceptors significantly affects
      proprioceptive properties of jaw muscle spindles via central neural mechanisms.
      The changes can have deleterious effects on oral motor function as well as
      kinesthetic sensibility.

PMID- 11323134
TI  - Activation of brainstem N-methyl-D-aspartate receptors is required for the
      analgesic actions of morphine given systemically.
AB  - The analgesic actions of opioids are in large part mediated by activation of
      brainstem pain modulating neurons that depress nociceptive transmission at the
      level of the dorsal horn. The present study was designed to characterize the
      contribution of N-methyl-D-aspartate (NMDA)- and non-NMDA-mediated excitatory
      transmission within the rostral ventromedial medulla (RVM) to the activation of
      brainstem inhibitory output neurons and analgesia produced by systemic morphine
      administration. The NMDA receptor antagonist D-2-amino-5-phosophonopentanoic acid
      (AP5), the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione
      disodium (CNQX) or saline was infused into the RVM of lightly anesthetized rats
      while recording the activity of identified pain modulating neurons: 'off-cells',
      thought to inhibit nociceptive transmission, and 'on-cells', thought to
      facilitate nociception. Nociceptive responsiveness (tail flick latency) was not
      affected by either antagonist. AP5, but not CNQX, attenuated or blocked
      activation and disinhibition of off-cells and the antinociception produced by
      systemically administered morphine. Reflex-related discharge of on-cells was
      unaffected by AP5, but significantly attenuated by CNQX. The present results
      highlight two important aspects of RVM pain modulatory circuits. First, morphine
      given systemically produces its analgesic effect at least in part by recruiting
      an NMDA-mediated excitatory process to activate off-cells within the RVM. This
      excitatory process may play a role in the analgesic synergy produced by
      simultaneous mu-opioid activation at different levels of the neuraxis. Second,
      reflex-related activation of on-cells is mediated by a non-NMDA receptor, and
      this activation does not appear to play a significant role in regulating reflex
      responses to acute noxious stimuli. Excitatory amino acid-mediated excitation
      thus has at least two distinct roles within the RVM, activating off-cells and on
      cells under different conditions.

PMID- 11323135
TI  - The density of remaining nerve endings in human skin with and without
      postherpetic neuralgia after shingles.
AB  - The mechanisms of chronic neuropathic pain are not well understood. Postherpetic
      neuralgia (PHN), which occurs in some patients after shingles (herpes zoster),
      was used to investigate the neural determinants of chronic pain. Skin biopsies
      were obtained from 38 adults with or without PHN at least 3 months after healing
      of shingles on the torso. Vertical sections were immunolabeled against PGP9.5, a
      pan-axonal marker, to measure the density of remaining nerve endings in skin
      previously affected by shingles. All axons that end in the epidermis are
      nociceptors, neurons that transmit pain messages. The densities ranged between 2
      and 3976 neurites/mm2 skin surface, but the overlap between subjects and without
      PHN was small. Of 19 subjects without PHN, 17 had more than 670 neurites/mm2 skin
      surface area (mean +/- SEM = 1569 +/- 230), and 18 of 19 subjects with PHN had
      640 or fewer neurites/mm2 (mean +/- SEM = 367 +/- 92). PHN may be a 'phantom
      skin' pain associated with loss of nociceptors. This threshold of approximately
      650 neurites/mm2 skin surface was not detected in previous studies that used
      summary statistics. It implies that the absence of pain after shingles may
      require the preservation of a minimum density of primary nociceptive neurons, and
      that the density of epidermal innervation may provide an objective correlate for
      the presence or absence of PHN pain.

PMID- 11323136
TI  - The LANSS Pain Scale: the Leeds assessment of neuropathic symptoms and signs.
AB  - This study describes the development and validation of a novel tool for
      identifying patients in whom neuropathic mechanisms dominate their pain
      experience. The Leeds assessment of neuropathic symptoms and signs (LANSS) Pain
      Scale is based on analysis of sensory description and bedside examination of
      sensory dysfunction, and provides immediate information in clinical settings. It
      was developed in two populations of chronic pain patients. In the first (n = 60),
      the use of sensory descriptors and questions were compared in patients with
      nociceptive and neuropathic pain, combined with an assessment of sensory
      function. This data was used to derive a seven item pain scale, consisting of
      grouped sensory description and sensory examination with a simple scoring system.
      The LANSS Pain Scale was validated in a second group of patients (n = 40) by
      assessing discriminant ability, internal consistency and agreement by independent
      raters. Clinical and research applications of the LANSS Pain Scale are discussed.

PMID- 11323137
TI  - Microsurgical DREZotomy for pain due to spinal cord and/or cauda equina injuries:
      long-term results in a series of 44 patients.
AB  - According to the literature estimations, 10-25% of patients with spinal cord and
      cauda equina injuries eventually develop refractory pain. Due to the fact that
      most classical neurosurgical methods are considered of little or no efficacy in
      controlling this type of pain, the authors had recourse to microsurgery in the
      dorsal root entry zone (DREZ). This article reports on the long-term results of
      the microsurgical approach to the dorsal root entry zone (DREZotomy) in a series
      of 44 patients suffering from unbearable neuropathic pain secondary to spine
      injury. The follow-up ranged from 1 to 20 years (6 years on average). The series
      includes 25 cases with conus medullaris, 12 with thoracic cord, four with cauda
      equina and three with cervical cord injuries. Surgery was performed in 37 cases
      at the pathological spinal cord levels that corresponded to the territory of the
      so-called 'segmental pain', and in seven cases, on the spinal cord levels below
      the lesion for 'infralesional pain' syndromes. The post-operative analgesic
      effect was considered to be 'good' when a patient's estimation of pain relief
      exceeded 75%, 'fair' if pain was reduced by 25-75%, and 'poor' when the residual
      pain was more than 75% of preoperative estimations. Immediate pain relief was
      obtained in 70% of patients and was long-lasting in 60% of the total series. The
      results varied essentially according to the distribution of pain. Good long-term
      results were obtained in 68% of the patients who had a segmental pain
      distribution, compared with 0% in patients with predominant infralesional pain.
      Regarding pain characteristics, a good result was obtained in 88% of the cases
      with predominantly paroxysmal pain, compared with 26% with continuous pain. There
      were no perioperative mortalities. Morbidity included cerebrospinal fluid leak
      (three patients), wound infection (two patients), subcutaneous hematoma (one
      patient) and bacteremia (in one patient). The above data justify the inclusion of
      DREZ-lesioning surgery in the neurosurgical armamentarium for treating
      'segmental' pain due to spinal cord injuries.

PMID- 11323138
TI  - Pain assessment in cognitively impaired and unimpaired older adults: a comparison
      of four scales.
AB  - The purpose of the study was to compare the psychometric properties of four
      established pain scales in a population of hospitalized older adults (mean age,
      76 years) with varying levels of cognitive impairment. Patients made ratings of
      current pain three times/day for 7 days. They also made retrospective daily,
      weekly, and bi-weekly ratings of usual, worst, and least pain levels over a 14
      day period. Ratings were made on four different scales, varying in numeric and
      verbal demands: a five-point verbal rating scale, a seven-point faces pain scale,
      a horizontal 21-point (0-100) box scale, and two vertical 21-point (0-20) box
      scales (measuring pain intensity and pain unpleasantness). The accuracy,
      reliability, construct validity, postdictive validity, and bias susceptibility of
      each scale were evaluated. The horizontal 21-point box scale emerged as the best
      scale with respect to both psychometrics and validity, regardless of mental
      status. Pain intensity did not vary as a function of mental status. Retrospective
      estimates of pain varied by mental status: a combination of usual/worst pain was
      best for cognitively impaired patients, while a combination of usual/least pain
      was best for unimpaired patients. These findings support the use of the 21-point
      box scale for pain assessment in older patients, including those with mild-to
      moderate cognitive impairment. They also support the ability of older,
      cognitively impaired patients to rate pain reliably and validly.

PMID- 11323139
TI  - Spatial discrimination thresholds for pain and touch in human hairy skin.
AB  - The traditional concept that pain is poorly localized has been challenged by
      recent studies, where subjects were able to point to the stimulated spot on the
      skin with an accuracy of 10-20 mm. Pointing movements themselves, however, have
      errors of about 15 mm. To determine the limits of sensory performance of the
      nociceptive system independent of motor performance, point localization of heat
      pain (540 mJ punctate laser stimuli, 5 mm diameter), mechanical pain (256 mN
      punctate probe, 200 microm diameter), and touch (16 mN von Frey probe, 1.1 mm
      diameter) were tested in a two-alternative forced-choice paradigm in 12 healthy
      subjects. Stimuli were applied in randomized order to two parallel lines on the
      back of the hand (4-32 mm distance). The cumulative distribution functions for
      correct localization were of similar sigmoid shape for all test stimuli,
      indicating logarithmic normal distributions. The 75% correct localization
      threshold for painful heat was 8.6 mm (3.1 +/- 0.1 log2 units) and did not differ
      significantly from that of non-painful touch (9.0 mm, 3.2+/-0.2 log2 units).
      Localization of mechanically-induced pain (5.1 mm, 2.4 +/- 0.2 log2 units) was
      significantly more accurate than both heat pain and touch, possibly due to a
      synergism of two different sensory channels, the tactile channel and the
      nociceptive channel, which were activated simultaneously. For all three stimuli,
      discrimination was significantly better in radial-ulnar compared to proximal
      distal direction, which might be related to oval receptive field shapes.
      Sequential spatial discrimination for touch was significantly better than
      simultaneous spatial discrimination tested with a grating orientation task (18.9
      mm), but both were one order of magnitude worse than at the finger tip (1.3 mm,
      0.4 +/- 0.1 log2 units). In conclusion, pain evoked by radiant heat pulses and
      touch evoked by von Frey probes were localized with similar precision on the back
      of the hand. These findings indicate that outside the tactile fovea at finger
      tips or lips the spatial discrimination capacities of the nociceptive and tactile
      systems are about equal.

PMID- 11323140
TI  - A cross-national study of the course of persistent pain in primary care.
AB  - Data from the World Health Organization's study of psychological problems in
      general health care were used to examine the course of persistent pain syndromes
      among primary care patients. Across 15 sites in 14 countries, 3197 randomly
      selected primary care patients completed baseline and 12-month follow-up
      assessments of pain, other somatic symptoms, and anxiety and depressive disorders
      (the Composite International Diagnostic Interview), and an assessment of
      occupational role disability (the Social Disability Schedule). Of patients with a
      persistent pain condition at baseline, 49% had not recovered 12 months later. The
      probability of non-recovery varied significantly across study centers and was
      significantly associated with the number of pain sites at baseline. After
      adjustment for age, sex, and study center, baseline anxiety or depressive
      disorder did not predict non-recovery of persistent pain. Among those without a
      persistent pain disorder at baseline, the rate of onset was 8.8% with a
      significant variability in risk across centers. The baseline characteristics
      predicting the onset of persistent pain disorder were psychological disorder,
      poor self-rated health, and occupational role disability. A persistent pain
      disorder at baseline predicted the onset of a psychological disorder to the same
      degree that a baseline psychological disorder predicted the subsequent onset of
      persistent pain. Persistent pain conditions are common among primary care
      patients, and the probability of resolution over 12 months is approximately 50%.
      We found a strong and symmetrical relationship between persistent pain and
      psychological disorder. Impairment of daily activities appears to be a central
      component of that relationship.

PMID- 11323141
TI  - The role of 5-hydroxytryptamine1A and 5-hydroxytryptamine1B receptors in
      modulating spinal nociceptive transmission in normal and carrageenan-injected
      rats.
AB  - Single unit extracellular recordings from the dorsal horn neurons were obtained
      with glass micropipettes in pentobarbital-anesthetized rats. A total of 115 wide
      dynamic range (WDR) neurons were studied in 94 rats. In normal rats, the size of
      nociceptive receptive fields (RFs) of WDR neurons was approximately 123.3 +/-
      8.21 mm2 (n = 88). Following carrageenan-induced inflammation, the RFs were
      markedly enlarged (332.4 +/- 30.1 mm2, n = 27, P < 0.001). The frequency of
      background activity of the WDR neurons in carrageenan-injected rats (11.3 +/- 2.1
      imp/s, n = 27) was greater than that in normal rats (7.1 +/- 0.8 imp/s, n = 88, P
      < 0.05). In 82% of WDR neurons in normal rats, there was a separation between the
      A- and C-responses. In contrast, in 67% of the neurons in carrageenan-injected
      rats, the response to suprathreshold electrical stimuli was a long train with no
      separation between the A- and C-responses. In carrageenan-injected rats, the
      magnitude and duration of the nociceptive responses were significantly increased
      compared to those in normal rats, and the average C-response threshold (7.7 +/-
      1.1 mA, n = 27) was lower than that in normal rats (10.4 +/- 0.7 mA, n = 88, P <
      0.05). Intrathecal injection of the 5-hydroxytryptamine(1A) (5-HT1A) receptor
      agonist 8-hydroxy-DPAT hydroxybromide (8-OH-DPAT) (0.305, 1.525, 3.05, and 15.25
      mM) dose-dependently increased Adelta- and C-responses and post-discharge in most
      of the WDR neurons. Following carrageenan-induced inflammation, the 8-OH-DPAT
      induced facilitatory effect on Adelta- and C-responses and post-discharge was
      significantly enhanced (P < 0.05). Intrathecal injection of the 5
      hydroxytryptamine1B (5-HT1) receptor agonist CGS12066A (0.222, 1.11, 2.22, and
      11.1 mM) dose-dependently enhanced the C-response and post-discharge without
      influencing the Adelta-response. In carrageenan-injected rats, CGS12066A not only
      enhanced the facilitatory effect on the C-response and post-discharge, but also
      facilitated the Adelta-response. Intrathecal injection of the 5-HT(1A) receptor
      antagonist NAN-190 (0.2 mM) alone did not influence Adelta- and C-responses and
      post-discharge of WDR neurons in normal rats. When 0.2 mM NAN-190 was co
      administered with 3.05 mM 8-OH-DPAT, the facilitatory effect of 8-OH-DPAT on
      Adelta- and C-responses and post-discharge was completely antagonized, whereas
      CGS12066A-induced facilitation on the C-response and post-discharge was not
      influenced by co-administration of 0.2 mM NAN-190 and CGS12066A. These data
      suggest that 5-HT1A and 5-HT1B receptor subtypes mediate the facilitatory effect
      of 5-HT on nociceptive processing in the spinal cord of rats. The excitability of
      dorsal horn WDR neurons and the sensitivity of the neurons to intrathecal 5-HT1A
      and 5-HT1B receptor agonists might increase following carrageenan-induced
      inflammation.

PMID- 11323142
TI  - Release of glutamate, nitric oxide and prostaglandin E2 and metabolic activity in
      the spinal cord of rats following peripheral nociceptive stimulation.
AB  - Peripheral tissue injury and inflammation may result in a facilitated spinal
      nociceptive transmission and central sensitization. Particularly, nitric oxide
      (NO) and prostaglandins (PGs) have been shown to be key mediators involved in the
      induction and maintenance of this state. By means of spinal cord microdialysis we
      have determined interstitial glutamate, NO (NO2-/NO3-), PGE2, glycerol, glucose
      and lactate concentrations in the dorsal horns of the spinal cord following
      peripheral nociceptive stimulation to gain further insight into the link between
      excitatory neurotransmitters and metabolic functions in the spinal cord during
      nociception. Formalin and zymosan injection into one hind paw evoked a biphasic
      release of glutamate and NO with the glutamate peaks preceding those of NO.
      Moreover, zymosan induced a biphasic increase of interstitial glycerol
      concentrations accompanied by an increase of interstitial lactate indicating
      metabolic disturbances. In contrast, formalin injection led to an elevation of
      dialysate glucose concentrations which may be interpreted as an indication of
      enhanced metabolic activity. The sequential release of glutamate and NO in the
      dorsal horns of the spinal cord in response to peripheral nociceptive stimulation
      supports the theory that NO may act as a retrograde transmitter. The metabolic
      changes observed after formalin and zymosan injection suggest that an intense
      peripheral nociceptive stimulation may not only activate but also disturb
      metabolic activity and possibly membrane integrity in the spinal cord.

PMID- 11323144
TI  - The association of hormone replacement therapy with experimental pain responses
      in postmenopausal women.
AB  - Considerable experimental research suggests that ovarian hormones can influence
      pain perception, and recent epidemiologic and clinical research suggests that
      exogenous hormone use may influence the prevalence and severity of clinical pain
      among women. However, to date no studies have examined the influence of hormone
      replacement therapy (HRT) on experimental pain responses and recent pain
      complaints among postmenopausal women. In this study, self-reported recent pain
      and general health were obtained, and thermal pain responses were assessed in
      three groups of healthy older adults: (1) women on HRT, (2) women not on HRT (No
      HRT), and (3) men. Results indicated no group differences in recent pain
      complaints or self-reported health, but differences emerged for measures of
      thermal pain perception. Specifically, HRT women showed lower pain thresholds and
      tolerances than No-HRT women and men, and the latter two groups did not differ
      from each other. The potential explanations and limitations of the observed
      findings are discussed.

PMID- 11323143
TI  - Chronic low-level administration of diquat increases the nociceptive response to
      gastric distension in rats: role of mast cells and tachykinin receptor
      activation.
AB  - Dietary factors can modulate visceral sensitivity and are suggested to interact
      with neuroimmune pathways. To determine whether daily low-level exposure to a
      food contaminant (diquat) alters sensitivity to gastric distension (GD) and the
      role of mast cells and tachykinin receptors activation, two series of experiments
      were conducted in eight groups of eight male Wistar rats (200-250 g) receiving
      daily doses of either diquat (0.1 mg/kg per day orally) or water for 21 days. In
      the first series, rats were sacrificed at the end of treatments and the gastric
      mucosal mast cell (MMC) number was histologically quantified. In the second
      series, after 21 days of treatment the cardiovascular depressor (CVD) response
      and corresponding gastric volumes were recorded under GD (from 10 to 40 mmHg).
      Doxantrazole (5 mg/kg intraperitoneally (i.p.)), a mast cell stabilizer, and SR
      140333 (1 mg/kg i.p.) and MEN 11420 (0.1 mg/kg intravenously), respectively NK1
      and NK2 receptor antagonists, were administered before GD. Before and after GD,
      blood samples were taken to measure blood histamine and the gastric MMC number
      was determined after sacrifice. Diquat treatment increased the MMC number. In
      diquat-treated rats, GD increased the CVD response and blood histamine level and
      induced MMC degranulation. Doxantrazole did not modify the hypersensitivity to GD
      but prevented mast cell degranulation. Both NK1 and NK2 receptor antagonists
      blocked the enhanced CVD response induced by diquat and prevented mast cell
      degranulation. None of the drugs had any effect in control animals. Prolonged
      exposure to a food contaminant at doses possibly found in food increases gastric
      sensitivity to distension, activates tachykinin receptors and results in MMC
      degranulation after GD.

PMID- 11323145
TI  - Effects of spinally delivered N- and P-type voltage-dependent calcium channel
      antagonists on dorsal horn neuronal responses in a rat model of neuropathy.
AB  - Neuropathic pain, due to peripheral nerve damage, can include allodynia
      (perception of innocuous stimuli as being painful), hyperalgesia (increased
      sensitivity to noxious stimuli) and spontaneous pain, often accompanied by
      sensory deficits. Plasticity in transmission and modulatory systems are
      implicated in the underlying mechanisms. The Kim and Chung rodent model of
      neuropathy (Kim and Chung, Pain 50 (1992) 355) employed here involves unilateral
      tight ligation of two (L5 and L6) of the three (L4, L5, and L6) spinal nerves of
      the sciatic nerve and reproducibly induced mechanical and cold allodynia in the
      ipsilateral hindpaw over the 14 day post-operative period. In vivo
      electrophysiological techniques have then been used to record the response of
      dorsal horn neurones to innocuous and noxious electrical and natural (mechanical
      and thermal) stimuli after spinal nerve ligation (SNL). Activation of voltage
      dependent calcium channels (VDCCs) is critical for neurotransmitter release and
      neuronal excitability, and antagonists can be antinociceptive. Here, for the
      first time, the effect of N- and P-type VDCC antagonists (omega-conotoxin-GVIA
      and omega-agatoxin-IVA, respectively) on the evoked dorsal horn neuronal
      responses after neuropathy have been investigated. Spinal omega-conotoxin-GVIA
      (0.1-3.2 microg) produced prolonged inhibitions of both the electrically- and low
      and high-intensity naturally-evoked neuronal responses in SNL and control rats.
      Spinal omega-agatoxin-IVA (0.1-3.2 microg) also had an inhibitory effect but to a
      lesser extent. After neuropathy the potency of omega-conotoxin-GVIA was increased
      at lower doses in comparison to control. This indicates an altered role for N
      type but not P-type VDCCs in sensory transmission after neuropathy and selective
      plasticity in these channels after nerve injury. Both pre- and post-synaptic
      VDCCs appear to be important.

PMID- 11323146
TI  - The effects of failure feedback and pain-related fear on pain report, pain
      tolerance, and pain avoidance in chronic low back pain patients.
AB  - The aim of this study was to investigate the influence of non-pain-related
      failure experiences and pain-related fear on pain report, pain tolerance and pain
      avoidance in chronic low back pain (CLBP) patients. Moreover, the mediating and
      moderating role of negative affectivity (trait-NA) in the relationship between
      failure experiences and pain was examined. Seventy-six patients were divided into
      high and low pain-related fear groups and within each group they were randomly
      assigned to the failure or success feedback condition. In the first part of the
      study patients completed a 'social empathy test' and experimenter 1 subsequently
      delivered false failure or success feedback. A second experimenter, who was blind
      for the condition, subsequently administered two lifting tasks in order to obtain
      measures of pain report, tolerance and avoidance. Failure feedback did have an
      effect on pain avoidance but unexpectedly, and not as hypothesized, pain
      avoidance was reduced instead of enhanced. With regard to pain report and pain
      tolerance similar patterns were found, but these were not statistically
      significant. The effect of failure feedback on pain avoidance was moderated by
      trait-NA. Only in the subgroup of patients who scored low on trait-NA did failure
      feedback decrease pain avoidance. State-NA did not mediate the effects of
      feedback. In line with previous findings, pain-related fear resulted in lower
      pain tolerance. Moreover, this study was the first to show that pain-related fear
      predicted higher pain report in CLBP patients. Pain-related fear did not predict
      pain avoidance when pre-lifting pain and gender were controlled for. Finally, pre
      lifting pain turned out to be the strongest predictor with regard to all pain
      measures. The role of pain-related fear and unexpected findings with regard to
      feedback are discussed as well as some clinical implications.

PMID- 11323147
TI  - Influence of painful chronic neuropathy on neurogenic inflammation.
AB  - The effect of topical application of capsaicin cream on neurogenic inflammation
      was investigated in a neuropathic pain model in rat. The neuropathic state was
      induced by loose ligation of the sciatic nerve with a chromic gut suture. A
      marked thermal hyperalgesia was observed in response to heat stimulation applied
      to the operated side from 3 days through 2 weeks, followed by a gradual return to
      the control level 35 days after surgery. In sham-operated animals, topical
      application of capsaicin cream to both sides of the hind paw, the instep and
      sole, as well as antidromic stimulation of the sciatic nerve led to a significant
      increase in the amounts of Evans blue and substance P (SP) released into the
      perfusates. This stimulus-induced extravasation was significantly suppressed by
      pretreatment with RP67580, an NK1 antagonist. On day 7 after ligation, capsaicin-
      and antidromic stimulation-induced extravasation were significantly reduced. At
      this time, both amount of SP released immediately after application of capsaicin
      and during antidromic stimulation were almost similar to that in sham-operated
      rats, whereas the basal amount of SP release significantly increased in ligated
      animals. In particular a major release of SP was detected immediately after the
      start of the perfusion compared with that in sham-operated rats. Plasma
      extravasation evoked by SP (10(-4) M) applied to the subcutaneous perfusate was
      significantly less in ligated than in sham-operated rats. These results suggest
      that nerve injury with chronic pain may produce increase in basal SP release into
      the peripheral tissues, and then such enhanced SP release cause reduction of SP
      induced extravasation.

PMID- 11323148
TI  - Projections from the marginal zone and deep dorsal horn to the ventrobasal nuclei
      of the primate thalamus.
AB  - It has been concluded recently that if a projection from the marginal zone to the
      ventral posterior lateral (VPL) nucleus exists, it is sparse. Given the
      importance of the marginal zone in nociception, this conclusion has raised doubts
      about the significance of the role of the ventrobasal complex in nociception. We
      have reexamined this projection using injections of the retrograde tracer,
      cholera toxin subunit B, into one side of the lateral thalamus in macaque
      monkeys. The injections were confined to the ventrobasal complex (with minimal
      spread to adjacent nuclei that do not receive spinal projections) in two animals.
      Many retrogradely labeled neurons were found in lamina I (as well as in lamina V)
      of the contralateral spinal and medullary dorsal horn. The results are consistent
      with the view that neurons in the marginal zone contribute prominently to the
      spinothalamic and trigeminothalamic projections to the VPL and ventral posterior
      medial (VPM) nuclei. This pathway is likely to be important for the sensory
      discriminative processing of nociceptive information with respect to the location
      and intensity of painful stimuli.

PMID- 11323149
TI  - The analgesic effect of codeine as compared to imipramine in different human
      experimental pain models.
AB  - The hypoalgesic effect of single oral doses of 100 mg imipramine and 125 mg
      codeine was evaluated in a randomised, placebo-controlled, double-blind, 3-way
      cross-over experiment including 18 healthy volunteers. Pain tests were performed
      before and 90, 180, 270, 360 and 450 min after medication. The tests included
      determination of pain tolerance thresholds to pressure, pain detection/tolerance
      thresholds to single electrical sural nerve stimulation and pain summation at
      tolerance threshold to repetitive electrical sural nerve stimulation (temporal
      summation) and pain experienced during the cold pressor test, rated as peak pain
      intensity, pain average intensity and discomfort. Compared to placebo, imipramine
      significantly increased pressure pain tolerance threshold (P = 0.03) and
      increased pain tolerance threshold (P = 0.05) and pain summation threshold (P =
      0.03), but not pain detection threshold to electrical stimulation. Imipramine did
      not cause significant changes in pain perception during the cold pressor test.
      Codeine significantly increased pressure pain tolerance threshold (P = 0.02),
      pain detection (P = 0.04) and pain tolerance threshold (P = 0.01) and pain
      summation threshold (P = 0.02) to electrical stimulation. In addition, codeine
      reduced the pain experienced during the cold pressor test (P = 0.04-0.003). It is
      concluded that both imipramine and codeine inhibit temporal pain summation,
      whereas only codeine reduces cold pressor pain. Pain summation may be a key
      mechanism in neuropathic pain. Imipramine has a documented effect on such pain
      conditions on temporal summation. The present study showed that codeine also
      inhibits temporal summation, which is in line with the clinical observations
      indicating that opioids relieve neuropathic pain.

PMID- 11323150
TI  - Childhood victimization and pain in adulthood: a prospective investigation.
AB  - Evidence of the relationship between childhood abuse and pain problems in
      adulthood has been based on cross-sectional studies using retrospective self
      reports of childhood victimization. The objective of the current study was to
      determine whether childhood victimization increases risk for adult pain
      complaints, using prospective information from documented cases of child abuse
      and neglect. Using a prospective cohort design, cases of early childhood abuse or
      neglect documented between 1967 and 1971 (n = 676) and demographically matched
      controls (n = 520) were followed into young adulthood. The number of medically
      explained and unexplained pain complaints reported at follow-up (1989-1995) was
      examined. Assessed prospectively, physically and sexually abused and neglected
      individuals were not at risk for increased pain symptoms. The odds of reporting
      one or more unexplained pain symptoms was not associated with any childhood
      victimization or specific types (i.e. sexual abuse, physical abuse, or neglect).
      In contrast, the odds of one or more unexplained pain symptoms was significantly
      associated with retrospective self-reports of all specific types of childhood
      victimization. These findings indicate that the relationship between childhood
      victimization and pain symptoms in adulthood is more complex than previously
      thought. The common assumption that medically unexplained pain is of
      psychological origin should be questioned. Additional research conducting
      comprehensive physical examinations with victims of childhood abuse and neglect
      is recommended.

PMID- 11323151
TI  - Central activation by histamine-induced itch: analogies to pain processing: a
      correlational analysis of O-15 H2O positron emission tomography studies.
AB  - The aim of this study was to identify the functional cerebral network involved in
      the central processing of itch and to detect analogies and differences to
      previously identified cerebral activation patterns triggered by painful noxious
      stimuli. Repeated positron emission tomography regional cerebral blood flow
      (rCBF) measurements using O15-labeled water were performed in six healthy right
      handed male subjects (mean age 32 +/- 2 years). Each subject underwent 12
      sequential rCBF measurements. In all subjects a standardized skin prick test was
      performed on the right forearm 2 min before each rCBF measurement. For
      activation, histamine was applied in nine tests in logarithmically increasing
      concentrations from 0.03 to 8%. Three tests were performed with isotonic saline
      solution serving as a control condition. Itch intensity and unpleasantness were
      registered with a visual analogue scale during each test. Subtraction analysis
      between activation and control conditions as well as correlation analysis with
      covariates were performed. Itch induced a significant activation in the
      predominantly contralateral somatosensory cortex and in the ipsilateral and
      contralateral motor areas (supplementary motor area (SMA), premotor cortex,
      primary motor cortex). Additional significant activations were found in the
      prefrontal cortex and the cingulate gyrus, but not in subcortical structures nor
      in the secondary somatosensory cortex. In correlation analyses, several cortical
      areas showed a graded increase in rCBF with the logarithm of the histamine
      concentration (bilateral sensorimotor areas and cingulate cortex; contralateral
      insula, superior temporal cortex and prefrontal cortex) and with itch
      unpleasantness (contralateral sensorimotor cortex, prefrontal cortex and
      posterior insula; ipsilateral SMA). Induction of itch results in the activation
      of a distributed cerebral network. Itch and pain seem to share common pathways (a
      medial and a lateral processing pathway and a strong projection to the motor
      system). In contrast to pain activation studies, no subcortical (i.e. thalamic)
      activations were detected and correlation analyses suggest differences in
      subjective processing of the two sensations.

PMID- 11323152
TI  - Computed tomography-guided neurolytic celiac plexus block with alcohol
      complicated by superior mesenteric venous thrombosis.
AB  - Neurolytic celiac plexus block (CPB) under radiological guidance is often
      performed to manage pain associated with pancreatic cancer. Serious complications
      related to the block are rare. Computed Tomography (CT)-guided neurolytic CPB is
      advocated to improve the efficacy of the block and to reduce the incidence of
      associated complications. We describe a case of superior mesenteric vein
      thrombosis associated with neurolytic CPB performed under CT guidance.

PMID- 11323153
TI  - Treatment of central post-stroke pain with oral ketamine.
AB  - Case report of 68 year old female with central post-stroke pain successfully
      treated with oral ketamine. The patient's pain was refractory to conventional
      pain treatments and she had persistent right hemi-body neuropathic pain with
      allodynia and hyperalgesia. An intravenous ketamine trial, followed by oral
      ketamine with titration to 50mg three times a day was beneficial in decreasing
      allodynia and hyperalgesia, as well as improving functional capabilities. Known
      side effects including dysphoria, hallucinations, and paranoid feelings were
      attenuated with benzodiazepines.

PMID- 11323155
TI  - College on problems of drug dependence. 63rd annual scientific meeting. June 16
      21, 2001, Scottsdale, Arizona. Abstracts.

PMID- 11323156
TI  - Molecular biology of the Ah receptor and its role in carcinogenesis.
AB  - The aryl hydrocarbon receptor (AhR) is a ligand-activated nuclear transcription
      factor that mediates responses to toxic halogenated aromatic toxins such as
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), polynuclear aromatic hydrocarbons,
      combustion products, and numerous phytochemicals such as flavonoids and indole-3
      carbinol (I3C). The nuclear AhR complex is a heterodimer containing the AhR and
      AhR nuclear translocator (Arnt) proteins, and the molecular mechanism of AhR
      action is associated with binding of the heterodimer to dioxin responsive
      elements (DREs) in regulatory regions of Ah-responsive genes. TCDD, a
      'xenodioxin', is a multi-site carcinogen in several species and possibly in
      humans, whereas natural AhR ligands including I3C and flavonoids tend to protect
      against cancer. Both TCDD and phytochemicals inhibit estrogen-induced breast and
      endometrial cancer, and the molecular mechanisms of this common response will be
      described.

PMID- 11323157
TI  - Peroxisome proliferator-activated receptor gamma (PPARgamma) activation and its
      consequences in humans.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) is a member of the
      superfamily of nuclear receptors. It binds and is activated by natural
      polyunsaturated fatty acids, eicosanoids, synthetic thiazolidinediones and
      related analogues. Biological effects exerted by PPARgamma ligands are mostly
      concerned with differentiation processes, sensitization to insulin and
      atherogenesis, and are paradigmatically ascribed to PPARgamma transactivation of
      PPARgamma-responsive genes. The PPARgamma paradigm and its consequences in humans
      are analyzed here in terms of the tissue specificity of PPARgamma, loss and gain
      of function mutants of PPARgamma, PPARgamma-responsive genes and clinical effects
      of PPARgamma ligands. Differentiation, as well as some of the atherogenic effects
      induced by PPARgamma ligands, does conform to the PPARgamma paradigm. However,
      sensitization to insulin as well as some of the antiatherogenic effects of
      PPARgamma ligands is not accounted for by PPARgamma activation, thus calling for
      an alternative target for insulin sensitizers.

PMID- 11323158
TI  - Anti-oestrogenic drugs and endometrial cancers.
AB  - Tamoxifen is one of the most effective drugs to be used in the treatment of women
      with breast cancer and as a chemopreventive agent in women 'at risk' from this
      disease. Tamoxifen can be regarded as a paradigm for a new range of selective
      oestrogen receptor modulators that include toremifene, used in the treatment of
      metastatic breast cancer and raloxifene, presently approved for use in
      postmenopausal women for the treatment of osteoporosis. Tamoxifen treatment of
      women leads to a small increase in the incidence of endometrial cancers. It is
      important to understand the mechanism for this side effect in order to predict
      the likely human risk for other drugs of this class. Two such mechanisms have
      been proposed: (1) conversion of the drug to electrophilic metabolites that
      damage cellular DNA; and (2) an oestrogen agonist action on the uterus, promoting
      endogenous lesions. In rats, long-term tamoxifen treatment results in liver
      cancer via a genotoxic mechanism. However, it seems most likely that, in women
      treated with tamoxifen, endometrial cancer is related to an oestrogen agonist
      effect of this drug, promoting uterine cell proliferation.

PMID- 11323159
TI  - The importance of drug-transporting P-glycoproteins in toxicology.
AB  - The importance of specific transport in toxicology is becoming increasingly clear
      and the work on P-glycoprotein has certainly been a major contribution to these
      growing insights. P-Glycoproteins were discovered by their ability to confer
      multidrug resistance in mammalian tumour cells. They are localised in the cell
      membrane where they actively extrude a wide range of compounds including many
      anti-cancer drugs from the cell. Besides in tumour cells, drug-transporting P
      glycoproteins are also expressed in a polarised fashion in normal tissues that
      perform an excretory or barrier function, such as the liver, kidneys, intestines,
      brain endothelial cells. Based on this expression profile, it has been proposed
      that P-glycoproteins are important in protecting the host by reducing exposure to
      xenobiotics. Further studies with P-glycoprotein knockout mice have clearly
      established this protective function. In general, the clearance of substrate
      drugs is lower in knockout mice due to a diminished hepatobiliary excretion,
      direct intestinal excretion and/or increased enterohepatic cycling. Moreover,
      their uptake in sanctuary sites, such as the brain or the foetus, was profoundly
      higher in P-glycoprotein knockout mice, as was the uptake of drugs from the
      gastro-intestinal tract into the systemic circulation following oral ingestion.
      These results clearly highlight the impact that transport proteins can play in
      toxicology.

PMID- 11323160
TI  - Characterisation of glucuronidation and transport in V79 cells co-expressing
      UGT1A1 and MRP1.
AB  - The co-ordinated glucuronidation and export of compounds from cells is an
      important determinant in the detoxification of many compounds in vivo. Many UDP
      glucuronosyltransferases (UGTs) and several multidrug resistance proteins (MRPs)
      have been cloned and individually expressed to assess specificity of
      glucuronidation and transport. However, to further understand the interplay
      between glucuronidation and transport we are developing stable cell lines that
      express different combinations of UGT and MRP isoforms. V79 cells expressing both
      UGT1A1 and MRP1 have been established. The ability of these cell lines to both
      glucuronidate and transport compounds was assessed ex vivo using estradiol and
      bilirubin as substrates.

PMID- 11323161
TI  - Up-regulation of transporters of the MRP family by drugs and toxins.
AB  - Expression of a variety of ABC efflux pumps including certain conjugate
      transporters of the multidrug resistance protein (MRP) subfamily is inducible in
      primate and rodent tissues, and in a variety of cell lines and primary cells in
      culture. In human cell lines (HepG2, MCF-7), we studied the inducibility of MRPs
      1-5. Similar to the rat mrp2 gene, human mrp2 is inducible by the chemical
      carcinogen 2-AAF, the chemotherapeutic drug cisplatin and the barbiturate
      phenobarbital, as demonstrated in Northern and Western Blots. Furthermore, the
      antibiotic rifampicin was identified as MRP2 inducer in HepG2 cells. MRP1 and 4
      mRNAs being expressed in human liver at a very low level could not be detected in
      HepG2 cells after treatment with various agents. However, MRP3 and 5 mRNAs were
      detected in addition to MRP2 and their expression was found to be increased by 2
      AAF, cisplatin and rifampicin. MRP1 expression was studied in MCF-7 cells where
      the chemotherapeutic drug vinblastine and tert-butyl hydroquinone but not the
      MRP2 inducing agents described above acted as inducers.

PMID- 11323162
TI  - Assessment of biotechnology products for therapeutic use.
AB  - Biotechnology products for therapeutic use include a very diverse range of
      products, including growth factors, cytokines, hormones, receptors, enzymes,
      clotting factors, monoclonal antibodies, vaccines, DNA vaccines, gene transfer
      products, cell therapies and tissue/organ grafts. While some of these products
      are regulated as medicinal products, the regulatory status of others such as some
      cell therapies and tissue/organ-based products differs globally and falls within
      the borderline between the practice of medicine, medical devices and medicinal
      products. The unclear regulatory status of some products can add to the
      complexity of the safety assessment of such products. Conventional non-clinical
      testing paradigms and guidelines for small molecule development are often not
      relevant for biotechnology products. Guidelines relating to the non-clinical
      safety evaluation of biotechnology products, gene transfer products and cell
      therapy products are available and represent a set of general guiding principals
      to be applied on a case-by-case basis. The quality, safety and efficacy of
      biotechnology products for therapeutic use are intricately linked, far more so
      than for conventional medicinal products, leading to the need for increased
      communication between those responsible for ensuring product quality and those
      responsible for non-clinical safety testing. Safety issues include
      microbiological safety (due to the use of biological materials either during the
      manufacturing process or as an integral part of the products), pharmacological/
      biological toxicity (due to excessive primary pharmacology or undesirable
      secondary pharmacology), immunogenicity and potential tumourigenicity (for
      example, for growth factors, immunosuppressive monoclonal antibodies and cell
      therapy products). Genotoxicity and intrinsic chemical toxicity are less of a
      problem for biotechnology products.

PMID- 11323163
TI  - Toxicological assessment of biological pesticides.
AB  - The majority of pesticides are based on synthetic chemicals. Regulatory
      assessments are performed by comparing the findings in a range of routine
      toxicity studies, designed for testing chemicals, with estimates of exposures.
      Recently there have been significant moves towards developing natural/biological
      alternatives. Biological pesticides (those based on viable organisms) present the
      regulator with a different set of challenges to those raised by most chemical
      pesticides. The concerns associated with biological pesticides can vary greatly
      from one organism to another, requiring an almost case-by-case approach. The
      known toxicity of certain bio-molecules and the pathogenicity of certain
      organisms underlines the need for a risk assessment of biological pesticides. The
      main aspects of a health risk assessment are characterisation of the organism,
      infectivity, pathogenicity, sensitisation and production of toxic secondary
      metabolites. Obtaining information or data on these areas is not always easy as
      there are no widely accepted test schemes or protocols for organisms, though
      guidelines are being developed for the European Commission (EC). Predicting
      exposure following pesticidal use of an organism is made more complex if it
      multiplies or secretes toxic metabolites. Reliable data on effects (lack of)
      associated with naturally occurring (background) exposures can sometimes provide
      considerable reassurance. This paper describes the background to the proposed EC
      scheme, which has much in common with current UK practices, and presents three
      examples of biological pesticides which have been assessed under the existing UK
      procedures.

PMID- 11323164
TI  - Recent developments in regulatory requirements for developmental toxicology.
AB  - A number of legislative and regulatory changes have occurred over the past 5
      years to prompt the re-evaluation of the regulatory requirements for
      developmental toxicity testing and use of the data for risk assessment. In
      particular, passage of the 1996 Food Quality Protection Act (FQPA) in the United
      States required the USEPA to evaluate children's health risks in a more rigorous
      fashion, and to apply an additional 10-fold safety factor if data were inadequate
      or children appeared to be more sensitive than adults. A review of the testing
      protocols required by USEPA led to extension of the dosing period to term in the
      prenatal developmental toxicity study and the addition of endpoints to the 2
      generation reproduction study protocol as indicators of possible neurologic,
      reproductive, or immune alterations. Revised testing guidelines for pesticides
      and toxic substances were published by USEPA in 1998, including a developmental
      neurotoxicity testing protocol. Further review for FQPA implementation resulted
      in the proposal for a core set of required toxicology studies, including routine
      developmental neurotoxicity, adult neurotoxicity, and adult immunotoxicity
      studies. In addition, development of new testing guidelines in several areas was
      recommended, these guidelines to be used in conjunction with or as follow-up when
      indicated from standard testing: developmental immunotoxicity, carcinogenesis,
      specialized neurotoxicity studies, endocrine disruptor studies, pharmacokinetics,
      and direct dosing of neonates. The impact of these efforts on the policies for
      toxicity testing of pesticides are discussed, and these issues are currently
      being reviewed on a broader scale, in particular, by evaluating the adequacy of
      the methods used for reference values (e.g. chronic RfD, RfC). Three major areas
      of focus for this review include life stages evaluated, endpoints assessed, and
      the duration of exposure used in various studies. A major focus of these efforts
      is to ensure that children's health risks are being adequately addressed in the
      risk assessment process.

PMID- 11323165
TI  - Towards ensuring the safety of vitamins and minerals.
AB  - Today, there is a clear need for a risk assessment for vitamins and minerals
      because the total daily intake for nutrients through regular food, fortified
      products (Functional Food) and supplements may very well reach critical levels
      for an individual consumer. Several expert panels of the European Union, the UK,
      Japan and China will publish their reports on this issue in the near future. The
      Food and Nutrition Board of the Institute of Medicine of the US/Canada has
      already published a new standard. The board has defined the so-called Tolerable
      Upper Intake Level (UL) as the highest level of daily intake that is likely to
      pose no risk of adverse health effects to almost all individuals in the general
      population. Their determination involves a multi-step risk assessment procedure
      on the basis of mainly human data. Several daily UL values that have already been
      published are of special interest, e.g. 1 mg folic acid, 50 microg vitamin D, 1 g
      vitamin E, 2 g vitamin C, 2.5 g calcium, 350 mg magnesium.

PMID- 11323166
TI  - Science, uncertainty and policy: food for thought.
AB  - The organisation and work of the Food Standards Agency are described. The Agency
      is a new non-Ministerial Government department with responsibility for protecting
      the health of the public and other interests of consumers in relation to food.
      Its roles encompass assessment of risk (through scientific expert committees) as
      well as risk communication and management. Among the many changes that the Agency
      has brought about is a new commitment to openness. All policy discussions and
      decisions take place in public. Diet and bovine spongiform encephalopathy are
      used as examples to illustrate the Agency's approaches to dealing with risk and
      uncertainty.

PMID- 11323167
TI  - The use of surrogate endpoints to assess potential toxicity in humans.
AB  - Data on toxic effects in humans may come from epidemiology studies, accidental
      poisonings, surveillance schemes or following intentional exposures. In many
      cases, a surrogate endpoint related to the adverse effect is investigated.
      Effects produced following intentional exposures are usually restricted to
      readily reversible, mild surrogate endpoints of the adverse effect of concern.
      Not all initial interactions within the target organ are related to the toxic
      effect, and many measurements are biomarkers of exposure not response. Biomarkers
      of response represent surrogate endpoints of response only if they are critical
      to the mode of action. The use of biomarkers and the possible problems with using
      surrogate endpoints are illustrated with data on aniline, cadmium, carbon
      monoxide, erythrosine, paracetamol (acetaminophen) and styrene. In vivo surrogate
      endpoints are normally used in risk assessment directly, whereas in vitro
      surrogate endpoints can be incorporated by the development of a biologically
      based dose-response model, or used to replace a default uncertainty factor by a
      chemical-specific adjustment factor.

PMID- 11323168
TI  - Toxicodynamic modelling and the interpretation of in vitro toxicity data.
AB  - The results of in vitro toxicity experiments are not easily extrapolated to
      'toxicological risk' for an intact organism. One of the most obvious differences
      between the situation in vitro and in vivo is the absence of the processes of
      absorption, distribution, metabolism and excretion that govern the exposure of
      the target tissues of the organism in vivo. The development of biokinetic models
      is aimed at estimating the relevant target tissue concentration of a compound. In
      our study, biokinetic models were constructed, where possible, solely on the
      basis of in vitro derived parameters for biotransformation as well as on
      partition coefficients determined or calculated from physicochemical structures.
      Another requirement is the existence of appropriate in vitro biological systems
      for the measurement of relevant effects. This requires a thorough knowledge of
      the possible mechanisms of toxic action, and of the physiology of the target
      organs. When these prerequisites are met (i.e. when the appropriate parameters
      can be quantified in a non-animal system), then an estimate of the dynamics in
      vitro can be made (e.g. as a critical active concentration). This will then
      result in a model describing a compound's dynamics. Eventually, the result of
      biokinetic and toxicodynamic models will need to be integrated in a compound's
      hazard and/or risk evaluation. A study carried out in the ECITTS programme showed
      promising results for the estimation of the acute and chronic systemic toxicity
      of a number of neurotoxic compounds.

PMID- 11323169
TI  - Human in vivo studies of non-pharmaceutical products.
AB  - Two principal types of human in vivo studies with non-pharmaceuticals can be
      distinguished: (1) human metabolism studies are used for identification of target
      metabolites which can subsequently be used in biological monitoring studies.
      Furthermore, they allow extrapolation from excretion of metabolite(s) to exposure
      to the parent compound on the basis of an understanding of human
      pharmacokinetics. (2) Pharmacodynamic or effect studies are restricted to the
      study of acute and inherently reversible changes and are most likely to improve
      risk assessment in the following areas: neurobehavioural effects (e.g. alcohol,
      organic solvents), alterations in biochemical markers (e.g. cholinesterase
      inhibition following organophosphate exposure) and topical effects (e.g. skin
      irritancy). Ethical considerations are of prime importance and, as a minimum, any
      human study must comply with the principles of the Declaration of Helsinki. The
      protocol should include scientifically sound objectives, a justification of
      subject numbers, a formal risk-benefit analysis and provisions for appropriate
      ethical review. The welfare of the individual participating in the study must be
      paramount. Informed consent has to be obtained and subjects must be free to
      withdraw from the study at any time. Compensation should be given for the
      inconvenience of participating in the study, but never for undergoing risk.
      Provided these conditions are met, human volunteer studies can be a powerful tool
      in risk assessment and risk management of exposure to non-pharmaceutical
      products.

PMID- 11323170
TI  - The use of toxicodynamics in risk assessment.
AB  - Risk assessment of xenobiotics is a qualitative and quantitative assessment of
      toxic properties conventionally based on data resulting from tests in animals
      exposed to the substance. The assessment of dose-effect relationship includes
      evaluation of exposure at the site of action. More recently, emphasis is put on
      understanding the relationship between exposure at the site of action and the
      resulting effect, i.e. toxicodynamic. In this respect, results from genotoxicity
      studies may be a measure for exposure and at the same time of an effect. Results
      of toxicodynamic endpoints such as binding to receptors or release of hormones
      have been used when replacing default values for interspecies extrapolation. It
      may also be envisaged to use toxicodynamic endpoints in order to get an estimate
      of intraspecies variability. It was demonstrated that this approach may be
      helpful only if the relationship between the toxicodynamic endpoint and the
      definite endpoint is known by using the example of bisphenol A. Whereas there are
      clear effects of bisphenol A in in vitro and ex vivo studies, the classical two
      generation study has not been able to detect an effect on reproduction and/or
      fertility. Looking in the future development of toxicodynamic endpoints, gene
      profiling and the analysis of proteins ('proteomics') may be helpful tools
      employed in screening and being related to the mode of action are explored for
      their suitability in terms of toxicodynamic endpoints.

PMID- 11323171
TI  - Environmental effects on genomic imprinting in mammals.
AB  - Genomic imprinting is an epigenetic marking mechanism by which certain genes
      become repressed on one of the two parental alleles. Imprinting plays important
      roles in mammalian development, and in humans its deregulation may result in
      disease and carcinogenesis. During different medical, technological and
      scientific interventions, pre-implantation embryos and cells are taken from their
      natural environment and subjected to culture in artificial media. Studies in the
      mouse demonstrate that environmental stress, such as in vitro culture, can affect
      the somatic maintenance of epigenetic marks at imprinted loci. These effects are
      associated with aberrant growth and morphology at fetal and perinatal stages of
      development.

PMID- 11323172
TI  - Genomic imprinting and cancer; new paradigms in the genetics of neoplasia.
AB  - The role of epigenetic modification of gene expression is becoming increasingly
      important in how we understand the loss of tumour suppressor gene function in a
      variety of tumours and tumour predisposing syndromes. This review explores the
      importance of epimutation in Beckwith-Wiedemann syndrome and Wilms' tumour and
      focuses on genomic methylation in both imprinted and non-imprinted genes as a key
      mechanism in the development of cancer.

PMID- 11323173
TI  - Gene imprinting in developmental toxicology: a possible interface between
      physiology and pathology.
AB  - Gene imprinting is an epigenetic mechanism for accomplishing persistent change in
      gene expression. In this brief paper, we explore the mechanisms for imprinting
      genes and present data showing that the synthetic estrogen, diethylstilbestrol
      (DES) can developmentally imprint genes by changing the pattern of DNA
      methylation. We further discuss the implications of this and other findings for
      non-mutagenic aspects of developmental toxicology, and suggest ways to use this
      concept in modifying in vitro screening for developmental toxicants.

PMID- 11323174
TI  - Food allergy: what are the issues?
AB  - With a growing interest in the development of genetically modified crop plants
      there is a need for appropriate approaches to safety assessment. Among the issues
      that have to be addressed is consideration of whether the products of novel genes
      have the potential to cause allergic sensitization. Resulting from a
      collaboration between the International Food Biotechnology Council and the
      International Life Sciences Institute recommendations have been made for a step
      wise approach to the assessment of allergenic potential based upon considerations
      of serological identity, and sequence or structural homology, with known
      allergens and examination of the stability of the test protein in a simulated
      gastric fluid. In parallel there has been interest in the development of animal
      models, which would permit a more direct evaluation of potential allergenic
      activity. Progress in these areas is reviewed briefly in the context of what is
      known of food allergy and some of the important issues, which must be addressed
      in designing safety assessment strategies identified.

PMID- 11323175
TI  - Determination of protein allergenicity: studies in rats.
AB  - For the safety evaluation of genetically engineered crops the potential
      allergenicity of the newly introduced protein(s) has become an important issue.
      There is, however, no universal and reliable test system for the evaluation of
      the allergenic potency of food products. The best known allergy assessment
      proposal is the careful stepwise process using the IFBC/ILSI decision tree.
      Unfortunately, the described tests are not always conclusive, especially if the
      gene source coding for the protein has no history of dietary use and/or an
      unknown history in terms of allergenicity. The further testing warranted should
      in particular be focused on the prediction of the sensitizing potential of the
      novel protein, for which animal models are considered to be needed. In this paper
      the results are summarized of a promising food allergy model developed in Brown
      Norway (BN) rats. The results demonstrate that BN rats can be sensitized orally
      to the various allergenic food proteins tested, resulting in significant antigen
      specific IgE responses, without the use of adjuvants. Upon oral challenge of
      previously sensitized animals, local and systemic immune-mediated effects, such
      as increased gastrointestinal permeability and decreased breathing frequency and
      blood pressure, could also be observed.

PMID- 11323176
TI  - Determination of protein allergenicity: studies in mice.
AB  - There is a need to identify and characterize the allergenic potential of novel
      proteins introduced into genetically-modified crop plants. Although several
      approaches have already been described, none of these measures directly the
      ability of proteins to cause allergic sensitization. For this reason there has
      been a growing interest in the development of suitable animal models. This
      article describes experience to date with a method based upon assessment of
      serological (IgG and IgE antibody) responses induced in BALB/c strain mice by
      proteins. Comparisons have been made between intraperitoneal (i.p.)
      administration and exposure by gavage using both allergenic and non-allergenic
      proteins. The available data indicate that responses provoked by i.p. exposure
      permit the identification of proteins that have the inherent potential to induce
      IgE antibody production and allergic sensitization. Moreover, this approach also
      provides a rank order of proteins with respect to allergenic potency that
      apparently reflects what is known of their relative sensitizing activity in
      humans. By comparison, oral exposure of mice by gavage is somewhat less
      sensitive. On this basis it is proposed that the inherent sensitizing potential
      of novel proteins can be evaluated as a function of IgE antibody responses
      stimulated by parenteral (i.p.) exposure of BALB/c mice.

PMID- 11323177
TI  - New models for assessing carcinogenesis: an ongoing process.
AB  - Traditionally, the use of rodent models in assessing the carcinogenic potential
      of chemicals has been expensive and lengthy, and the relevance of the
      carcinogenic effect to humans is often not fully understood. Today, however, with
      the rapid advances in molecular biology, genetically altered mice containing
      genes relevant to humans (e.g. oncogenes, tumor suppressor genes) and reporter
      genes (e.g. lacI) provide powerful tools for examining specific chemical-gene
      interactions thereby allowing a better understanding of the mechanisms of
      carcinogenesis in a shorter period of time. This paper will cover an overview of
      ongoing validation efforts, followed by examples of studies using several
      genetically engineered models including the p53def mouse model and the Big Blue
      transgenic mouse model. Specifically, examples where transgenic models were
      integrated into the testing program based on specific hypotheses dealing with
      genetic alterations in cancer genes and reporter genes will be discussed. The
      examples will highlight possible ways genetically altered mice may be integrated
      into a comprehensive research and testing strategy and thereby provide an
      improved estimation of human health risks.

PMID- 11323179
TI  - The role of nucleotide excision repair and loss of p53 in mutagenesis and
      carcinogenesis.
AB  - Xpa mice, which have a completely defective nucleotide excision repair (NER)
      pathway, have a cancer predisposition when exposed to several carcinogens. NER is
      one of the major DNA repair pathways in the mammalian cell, and is involved in
      the removal of a wide variety of DNA lesions, such as those induced by UV light,
      bulky adducts and DNA crosslinks. To study the role of NER in both mutagenesis
      and carcinogenesis, NER-defective Xpa mice were crossed with transgenic
      lacZ/pUR288 mutation-indicator mice. Furthermore, the relationship between the
      tumor suppressor gene p53, NER, induction of mutations and tumor development was
      studied in Xpa/p53+/-/lacZ triple transgenic mice. Using the genotoxic
      carcinogens benzo[a]pyrene (B[a]P) and 2-acetylaminofluorene (2-AAF), it is shown
      that mutations in the inactive (non-transcribed) lacZ reporter gene reliably
      predict cancer risk. In tissues at risk for the development of tumors, increased
      mutant frequencies could be found at much earlier stages. A heterozygous loss of
      p53 appears to act synergistically to a NER defect, both in mutation- as well as
      tumor-induction. Surprisingly, however, the effect of a heterozygous loss of p53
      appeared to be tissue-restricted, being apparent in the bladder but absent in
      liver and spleen.

PMID- 11323178
TI  - The use of gene knockout mice to unravel the mechanisms of toxicity and chemical
      carcinogenesis.
AB  - Metabolism of toxins and carcinogens is carried out by large groups of xenobiotic
      metabolizing enzymes. These enzymes are generally considered to be required for
      elimination of xenobiotics such as drugs, dietary chemicals and environmental
      pollutants, and to be required for chemical toxicity and carcinogenicity. An
      important role for these enzymes in metabolism of endogenous chemicals has not
      been established. Mouse lines in which the genes encoding several xenobiotic
      metabolizing enzymes were knocked out were produced and are being used to
      determine the role of metabolism in carcinogenesis, and acute and chronic
      toxicities in vivo. Mouse lines lacking the P450s CYP1A1, CYP1A2, CYP1B1 and
      CYP2E1, microsomal epoxide hydrolase (mEH), NADPH:quinone oxidoreductase and the
      glutathione S-transferase P1 have no deleterious phenotypes, indicating that
      these enzymes are not required for mammalian development and physiological
      homeostasis. However, when challenged with toxins and carcinogens, they respond
      differently from their wild-type (WT) counterparts. For example, mice lacking
      CYP1A2 and CYP2E1 are totally resistant to acetaminophen-induced hepatotoxicity.
      Mice lacking CYP1B1 or mEH are less responsive to tumorigenesis by 7,12
      dimethybenz[a]anthracene. However, CYP1A2-null mice do not significantly differ
      from WT mice in their response to the hepatocarcinogen 4-aminobiphenyl. These and
      other studies indicate that the xenobiotic-metabolism null mice are of great
      value in the study of the mechanisms of chemical injury.

PMID- 11323180
TI  - Hormones and testis development and the possible adverse effects of environmental
      chemicals.
AB  - Development of a fetus into a phenotypic male depends, first, on testis formation
      and second, on hormone production by the fetal testis. Disorders of testicular
      hormone production or action can lead in severe cases to phenotypic abnormalities
      or can predispose towards impaired reproductive health. Evidence for
      deteriorating human male reproductive health, especially an increase in
      testicular cancer, points to disturbed (hormonal) development of the fetal
      testis. By comparison of testicular dysgenesis in humans and exposure to certain
      phthalates in fetal rats, the similarities in outcomes and testicular cell-cell
      disruption are highlighted as are the pathways via which oestrogenic and
      (especially) anti-androgenic environmental chemicals might act to induce such
      changes. The susceptibility of sperm production in adulthood to 'hormonal'
      disruption in fetal and neonatal life is also discussed. Though it is concluded
      that no direct evidence links human exposure to environmental chemicals and male
      reproductive disorders that stem from disturbed testis development, this is based
      mainly on lack of information. Using the example of phthalates, for which new
      data have emerged, it is argued that until the appropriate in vivo studies are
      undertaken, the safety of hormonally active environmental chemicals, especially
      in mixtures, will continue to give cause for concern as far as testicular
      development is concerned.

PMID- 11323181
TI  - Testing for endocrine disruption post-EDSTAC: extrapolation of low dose rodent
      effects to humans.
AB  - The study of chemically-induced endocrine disruption in mammals is a relatively
      new field of endeavour, and it has been assailed by an unusual level of
      disagreement among investigators regarding the developmental effects produced by
      chemicals in animals. This article discusses the several sources of uncertainty
      in endocrine toxicity studies, and the intrinsic variability of many of the key
      experimental parameters. It is concluded that current uncertainties regarding
      extrapolation of rodent effects to humans are due to the absence of an extensive
      agreed rodent control database for the developmental parameters under study,
      coupled to the established intrinsic variability of these parameters between
      strains/species of test animals and test protocols. Only when these factors are
      generally accepted and well studied will it be possible to relate effects seen in
      rodents to humans.

PMID- 11323182
TI  - Use of positron emission tomography in analysing receptor function in vivo.
AB  - The non-invasive radiotracer technique positron emission tomography (PET) may
      provide valuable information in the toxicokinetic-toxicodynamic evaluation of
      endogenous or toxic environmental compounds. Assessment of mechanism of action of
      toxins is often difficult to validate. In this respect, PET may offer advantages
      since it can quantify not only the distribution and kinetics of the radiolabelled
      toxin in the body, but also the altered rates of physiological or biochemical
      processes induced by the toxin. It is even possible to validate the body
      distribution and tissue accumulation of the toxic compound in primates, since
      linear kinetics can be assumed after administration of the radiolabelled compound
      in minute amounts without any toxic or physiological effects. Quantitative
      estimates can be derived with accuracy and high precision. Using a multi-tracer
      protocol, it is often possible to illuminate both the kinetics and the dynamics
      of a toxic compound. Long-term effects of different toxins on dopamine receptor
      function have been evaluated with PET as well as the influence of Parkinson
      disease medication on pre- and postsynaptic dopaminergic receptor function over
      the course of the disease. In conclusion, PET may provide very informative
      insight into complex receptor interactions of both toxic compounds and drugs
      under development.

PMID- 11323183
TI  - Applications of in vivo electron paramagnetic resonance (EPR) spectroscopy:
      measurements of pO2 and NO in endotoxin shock.
AB  - Recent developments of EPR instrumentation that allow the use of large tissue
      samples or whole animals and the ability to image spatially resolved EPR signals
      has led to novel applications of EPR spectroscopy in vivo. Utilising a 1 GHz EPR
      spectrometer with a 3.4-cm birdcage resonator, it was possible to detect and
      measure nitric oxide and oxygen in the livers of mice with lipopolysaccharide
      (LPS)-induced septic shock. Nitric oxide was detected as the nitric oxide (NO)
      complex of Fe-diethyldithiocarbamic acid (Fe-DETC) while pO2 was measured from
      the EPR linewidth of the oxygen-sensitive coal material 'gloxy'. LPS treatment
      stimulated the production of nitric oxide in the liver and the general
      circulation and the oxygenation of liver tissue was decreased. Selective
      placement of the EPR probes allowed images of nitric oxide and oxygen to be
      obtained in the liver. The spectral and spatial information obtained with this
      technique will allow improved understanding of the pathophysiology of such
      diseases.

PMID- 11323184
TI  - Genetic variability in susceptibility and response to toxicants.
AB  - Xenobiotic metabolism is carried out by phase I and phase II enzymes which are to
      a large extent polymorphic. The majority of cytochrome P450 (CYP) enzymes
      involved in xenobiotic metabolism are polymorphic and inducible, resulting in
      abolished, quantitatively or qualitatively altered or enhanced drug metabolising
      activity. Stable duplication, multiduplication or amplification of active genes
      have been described. In mouse models it is apparent that inactivation of specific
      enzymes active in xenobiotic metabolism can affect the risk for cancer
      development in relation to specific xenobiotic exposure, whereas the situation in
      humans is far more complex. The polymorphism of CYP enzymes is expected to
      influence individual sensitivity and toxicity for different environmental agents,
      although there is as yet no real consensus in the literature about specific firm
      relationships in this regard. The incidence of serious and fatal adverse drug
      reactions (ADRs) has been found to be very high among hospitalised patients, the
      cost of ADRs to society is large and they are responsible for 5-10% of all
      hospital admissions. It is likely that predictive genotyping could avoid 10-20%
      of ADRs. In the present contribution an overview is presented regarding our
      present knowledge about the polymorphism of phase I enzymes, with emphasis on
      xenobiotic metabolising CYPs and the importance for metabolic activation of
      xenobiotics.

PMID- 11323185
TI  - Genetic variability in susceptibility and response to toxicants.
AB  - Everyone has a unique combination of polymorphic traits that modify
      susceptibility and response to drugs, chemicals and carcinogenic exposures. The
      metabolism of exogenous and endogenous chemical toxins may be modified by
      inherited and induced variation in CYP (P450), acetyltransferase (NAT) and
      glutathione S-transferase (GST) genes. We observe that specific 'at risk'
      genotypes for GSTM1 and NAT1/2 increase risk for bladder cancer among smokers.
      Genotypic and phenotypic variation in DNA repair may affect risk of somatic
      mutation and cancer. Variants of base excision and nucleotide excision repair
      genes (XRCC1 and XPD) appear to modify exposure-induced damage from cigarette
      smoke and radiation. We are currently engaged in discovering genetic variation in
      environmental response genes and determining if this variation has any effect on
      gene function or if it is associated with disease risk. These and other results
      are discussed in the context of evaluating inherited or acquired susceptibility
      risk factors for environmentally caused disease.

PMID- 11323186
TI  - Toxicogenetics in drug development.
AB  - The major progress made in the understanding of the genetic basis of inter
      individual variation in drug response, alongside the rapid advances in
      technology, provides major new opportunities to ensure the safe introduction of a
      new chemical entity into clinical practice. In essence, the aim is to get the
      right drug into the right patient using knowledge of factors that influence both
      benefit and risk. The stage of the drug development process at which genetic
      analysis needs to be undertaken is dependent on the frequency of the event, and
      the availability of clinical samples. Thus, common adverse events, or assessment
      of efficacy, will be feasible for testing in phases I-III. However, when a rare
      event is being studied, for example idiosyncratic toxicity, prospective analysis
      becomes impossible. Thus, retrospective studies using available drugs is
      important as it may provide paradigms for future drug development. Additionally,
      prospective collection of samples will be important so that rare adverse events
      identified during phase IV can then be analysed using toxicogenetic approaches.
      Ultimately, information obtained from toxicogenetics must be included in the
      Specific Product Characteristics (SPC) and thus formally translated into clinical
      practice in order to contraindicate the drug in specific patients with a
      genetically determined susceptibility to drug toxicity.

PMID- 11323187
TI  - Experimental approaches to the determination of genetic variability.
AB  - Toxicology is concerned with the interaction between xenobiotics and biological
      molecules directly or indirectly coded in the DNA, and can be regarded as a
      branch of genetics. There is genetic variation in these interactions, which has
      important implications for risk assessment and because it can be used as a tool
      in studying toxic mechanisms. The genetics of susceptibility can be studied by
      forward or reverse genetics. Forward genetics involves working from an observed
      phenotype such as susceptibility to a particular xenobiotic and identifying the
      susceptibility genes. Often, this involves mapping and identifying quantitative
      trait loci, as most toxic responses have a polygenic mode of inheritance. The use
      of inbred strains is almost essential. Reverse genetics involves starting with a
      known genetic polymorphism and determining its effects on the response to
      xenobiotics. Studies of 'knockout' animals are a good example, although there are
      many naturally occurring polymorphisms that may affect toxic responses. In both
      cases, care has to be taken to ensure that the genetic background is carefully
      controlled in any comparison between animals thought to be carrying susceptible
      and resistant alleles.

PMID- 11323188
TI  - Role of cytokines in non-genotoxic hepatocarcinogenesis: cause or effect?
AB  - Chemicals with the potential to cause cancer through damaging DNA can be readily
      identified in a range of in vitro screens that detect genotoxicity. However, many
      carcinogens are non-genotoxic yet cause rodent tumours, particularly in the
      liver. Some non-genotoxic carcinogens such as the peroxisome proliferators (PPs)
      act directly to cause liver growth and proliferation, whereas others such as
      carbon tetrachloride cause liver damage, followed by regenerative hyperplasia.
      Current data support a role for cytokines such as tumour necrosis factor alpha
      (TNFalpha) and interleukin 1 (IL1) in hepatocarcinogenesis. However, these data
      give rise to conflicting hypotheses; in some experimental models, TNFalpha
      appears to mediate damage, whereas in others it is postulated to play a role in
      tissue repair. Recently, we have shown that TNFalpha acting via TNFalpha receptor
      1 and p38 MAP kinase suppresses hepatocyte apoptosis. However, when new protein
      synthesis is disabled, TNFalpha becomes a death signal. An understanding of the
      role of cytokines in rodent hepatocarcinogenesis will allow the development of
      markers that can be used to identify, at an early stage, those chemicals with the
      potential to induce rodent tumours.

PMID- 11323189
TI  - Liver toxicity and apoptosis: role of TGF-beta1, cytochrome c and the apoptosome.
AB  - Transforming growth factor-beta1 (TGF-beta1), is involved in controlling liver
      size, by inducing apoptotic cell death in hepatocytes. However the mechanism by
      which TGF-beta(1) induces caspase activation and cell death is unknown. Apoptosis
      can be initiated either by receptor-mediated (e.g. Fas/CD95) or non-receptor
      chemically mediated (stress-induced) processes. With Fas/CD95 receptor mediated
      cell death, a multi-protein complex (DISC) is assembled at the plasma membrane,
      which activates the downstream caspases and cell death. In stress-mediated
      apoptosis, a cytosolic DISC equivalent, the apoptosome is formed that activates
      the effector caspases. We have characterised this complex in THP.1 cells, and
      shown that this is a cytochrome c dependent process that induces the formation of
      an approximately 700 kDa apoptosome caspase processing complex. This is formed by
      oligomerisation of apoptotic protease-activating factor 1 (Apaf-1), and
      recruitment and processing of caspase-9. We have now shown that TGF-beta1-induced
      apoptosis also occurs via the release of cytochrome c and the subsequent
      oligomerisation of Apaf-1 into an approximately 700 kDa apoptosome complex. Our
      studies show that, even though TGF-beta1 induction of apoptosis is a receptor
      mediated event, it operates through the mitochondrial/Apaf-1 caspase activation
      pathway that appears to act as a common execution pathway for many diverse
      apoptotic stimuli.

PMID- 11323190
TI  - Role of inflammation in chemical-induced hepatotoxicity.
AB  - The liver, which is the major organ responsible for the metabolism of drugs and
      toxic chemicals, is also the primary target organ for many toxic chemicals.
      Increasing evidence has indicated that inflammatory processes are intimately
      involved in chemical-induced hepatotoxic processes, and like other inflammatory
      diseases, such as autoimmunity, are responsible for producing mediators that can
      effect liver damage or repair. This review will summarize our current
      understanding of how inflammatory processes influence hepatic pathology and
      repair following exposure to established hepatotoxic chemicals including carbon
      tetrachloride, an industrial chemical, and acetaminophen, a widely used
      analgesic.

PMID- 11323191
TI  - Health risks from the use of mobile phones.
AB  - Widespread concerns have been raised about the possibility that exposure to the
      radiofrequency (RF) fields from mobile telephones or their base stations could
      affect people's health. Such has been the rapid growth of mobile
      telecommunications that there will be about one billion mobile phone users before
      2005. Already there are more mobile than fixed-line users. Developing countries
      are establishing mobile telecommunications rather than the more expensive fixed
      line systems. Thus, if there is any impact on health from mobile telephones, it
      will affect everyone in the world. The World Health Organization (WHO)
      established the International EMF Project in 1996 to evaluate the science,
      recommend research to fill any gaps in knowledge and to conduct formal health
      risk assessments of RF exposure once recommended research had been completed. In
      addition, the UK government established an independent expert group to review all
      the issues concerning health effects of mobile telephones and siting of base
      stations. Cancer has been suggested as an outcome of exposure to mobile
      telephones by some scientific reports. This paper reviews the status of the
      science and WHO's programme to address the key issues. In addition, the main
      conclusions and recommendations of the UK expert group will be summarised.

PMID- 11323192
TI  - Idiopathic environmental intolerances (IEI): myth and reality.
AB  - The psychogenic theory presupposes that idiopathic environmental intolerance
      (IEI) is an overvalued idea explained by psychological and psychosocial
      processes. The polysomatic symptoms are amplifications of complaints common to
      the general population, psychophysiological manifestations of stress and the
      stress-response, or symptoms of psychiatric clinical syndromes. The psychogenic
      theory is supported by provocation challenge studies which demonstrate that
      appraisals of 'reactions' are unreliable and cognitively mediated. Clinical
      studies of IEI cases consistently identify greater incidence of current and
      premorbid lifetime psychiatric disorders and co-morbidity with functional somatic
      syndromes that are fashionable 'diagnoses'. The toxicogenic theory presupposes
      low-level chemical sensitivity or intolerance without objective signs to a
      plethora of diverse chemical agents. Symptoms are synonymous with disease and
      attributions are synonymous with cause. Hypotheses about physiological processes
      and mechanisms are implausible and unsupported by evidence. Advocates claim this
      phenomenon is so ephemeral that the principles and methods of toxicology do not
      apply and that a scientific paradigm shift is in order.

PMID- 11323193
TI  - The potential for toxic effects of chronic, low-dose exposure to
      organophosphates.
AB  - Organophosphorus esters have the potential to produce several forms of toxicity.
      Most produce acute intoxication as a result of inhibition of acetylcholinesterase
      and, if severe, this can have longer lasting secondary consequences such as
      intermediate syndrome, or even permanent disability. Some esters produce a very
      specific syndrome of delayed peripheral neuropathy. This neuropathy is always
      preceded by severe acute intoxication, except in the case of a few specific
      agents such as tri-o-cresyl phosphate. All of these effects are reasonably well
      understood and show a dose threshold. Chronic low level exposure in non-poisoned
      subjects has been associated with impaired neurobehavioral performance in some,
      but not all, epidemiological studies. The mechanisms involved are not well
      understood, but if organophosphates do play a causal role, this will not
      necessarily be via acetylcholinesterase inhibition. Doses too low to produce
      cholinergic signs have been shown to produce a variety of effects in experimental
      animals ranging from enhanced maze learning to slowed nerve conduction. It is
      likely that other, more sensitive, brain proteins are the targets for such
      actions. Effects mediated via such target proteins would be expected to show very
      different structure-activity relationships to acute toxicity mediated by
      acetylcholinesterase. Hence epidemiological studies expecting similar (class)
      effects from low-dose exposure to different organophosphorus esters may produce
      variable results or false negatives.

PMID- 11323194
TI  - Application of genomics to the definition of the molecular basis for toxicity.
AB  - Transcript profiling technology enables quantitative measurement of the
      transcriptional activity of potentially thousands of genes in biological samples.
      The application of such technology to toxicology, toxicogenomics, promises
      substantial dividends in mechanistic toxicity research and also, possibly, the
      ability to predict adverse toxicity for novel or untested compounds. Our
      laboratory has developed a custom approach to this technology, designing cDNA
      microarray platforms specifically for gene expression events of relevance to a
      large number of toxicological endpoints. Such arrays allow comprehensive coverage
      of genes associated with entire pathways (such as oxidative stress, signal
      transduction, stress response, epithelial biology) and enable simultaneous
      measurement of more than ten thousand gene expression events.

PMID- 11323195
TI  - Microarray analysis of hepatotoxins in vitro reveals a correlation between gene
      expression profiles and mechanisms of toxicity.
AB  - A rate-limiting step that occurs in the drug discovery process is toxicological
      evaluation of new compounds. New techniques that use small amounts of the
      experimental compound and provide a high degree of predictivity would greatly
      improve this process. The field of microarray technology, which allows one to
      monitor thousands of gene expression changes simultaneously, is rapidly advancing
      and is already being applied to numerous areas in toxicology. However, it remains
      to be determined if compounds with similar toxic mechanisms produce similar
      changes in transcriptional expression. In addition, it must be determined if gene
      expression changes caused by an agent in vitro would reflect those produced in
      vivo. In order to address these questions, we treated rat hepatocytes with 15
      known hepatoxins (carbon tetrachloride, allyl alcohol, aroclor 1254,
      methotrexate, diquat, carbamazepine, methapyrilene, arsenic, diethylnitrosamine,
      monocrotaline, dimethyl-formamide, amiodarone, indomethacin, etoposide, and 3
      methylcholanthrene) and used microarray technology to characterize the compounds
      based on gene expression changes. Our results showed that gene expressional
      profiles for compounds with similar toxic mechanisms indeed formed clusters,
      suggesting a similar effect on transcription. There was not complete identity,
      however, indicating that each compound produced a unique signature. These results
      show that large-scale analysis of gene expression using microarray technology has
      promise as a diagnostic tool for toxicology.

PMID- 11323196
TI  - Cholesterol biosynthesis regulation and protein changes in rat liver following
      treatment with fluvastatin.
AB  - The enzyme 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase is a key
      regulator in cholesterol biosynthesis and HMG CoA reductase inhibitors (statins)
      have become a widely prescribed family of lipid lowering agents. Cholesterol
      synthesis occurs predominantly in liver which is the target organ of statins. We
      studied the effects of fluvastatin (Lescol), a member of the statin family, on
      hepatic protein regulation. Male F344 rats treated with 0.8 mg/kg per day
      fluvastatin or 24 mg/kg per day fluvastatin for 7 days showed treatment-related
      changes in 58 liver proteins (P<0.005). Major effects were evident in the
      cholesterol biosynthesis pathway including the induction of enzymes upstream and
      downstream of the target enzyme HMG CoA reductase. Treatment also triggered
      alterations in key enzymes of carbohydrate metabolism and was associated with
      changes in a heterogeneous set of cellular stress proteins involved in
      cytoskeletal structure, calcium homeostasis and protease activity. The latter set
      of protein alterations indicates that hepatotoxicity is associated with high-dose
      treatment. Based on the results it is suggested that HMG-CoA synthase and
      isopentenyl-diphosphate delta-isomerase may be explored as alternative drug
      targets and that the induction levels of these enzymes may serve as a measure of
      potency of individual statin drugs. It is proposed that efficacy and cellular
      stress markers discovered in this study may be used in a high throughput screen
      (HTS) assay format to compare efficiently and accurately the therapeutic windows
      of different members of the statin family.

PMID- 11323197
TI  - Proteomic profiling from human samples: the body fluid alternative.
AB  - Proteomics is one of the technologies rapidly changing our approach to drug
      development. The applications of proteomics, particularly with reference to
      analysis of body fluid samples, will be described. Proteomic analysis involves
      the systematic separation, identification and characterisation of proteins
      present in a biological sample. By comparing the proteins present in diseased
      samples with those present in normal samples, it is possible to identify changes
      in expression of proteins that potentially may be related to organ toxicity.
      Proteomics is regarded as a sister technology to genomics. Although the pattern
      of gene activity will be abnormal in a tissue with a pathological lesion, there
      can be a poor correlation between the level of activity of different genes and
      the relative abundance within the tissue of the corresponding proteins. This is
      especially true where the mode of action of the test material interferes with
      protein synthesis and/or post translational modification. Consequently, the
      information about a pathological process that can be derived at the level of gene
      activity is incomplete. Proteomics has now made it possible to analyse proteins
      using high throughput, automated techniques. Although both mRNA and proteomic
      profiling can be applied to tissue samples, analysis of body fluids (e.g. serum,
      urine, CSF, synovial fluid) is restricted to proteomics. In these cases the
      protein composition is derived from many tissues and processes. Proteomic
      analysis can yield information on disease processes and potential response to
      treatment. Examples will be presented of the identification of surrogate markers
      for hepatocellular carcinoma, breast cancer, from cerebrospinal fluid in humans
      and gentamicin toxicity in the rat.

PMID- 11323198
TI  - Applications of population approaches in toxicology.
AB  - Many experimental or observational studies in toxicology are best analysed in a
      population framework. Recent examples include investigations of the extent and
      origin of intra-individual variability in toxicity studies, incorporation of
      genotypic information to address intra-individual variability, optimal design of
      experiments, and extension of toxicokinetic modelling to the analysis of
      biomarker studies. Bayesian statistics provide powerful numerical methods for
      fitting population models, particularly when complex mechanistic models are
      involved. Challenges and limitations to the use of population models, in terms of
      basic structure, computational burden, ease of implementation and data
      accessibility, are identified and discussed.

PMID- 11323199
TI  - Endpoints and surrogates for use in population studies in toxicology.
AB  - Risk characterisation of human exposure to chemicals requires information on the
      intrinsic toxic (hazardous) properties of the chemical, dose response of effects
      for the critical endpoints and exposure of the population. Information on
      hazardous properties, including data on mechanism and toxicokinetics, is
      necessary to define the critical endpoints and the relevant parameters to assess
      internal exposure and its relation to external exposure. Consequently the design
      of population studies to evaluate toxic effects or to monitor exposed cohorts
      must consider the critical endpoints of toxic effects and exposure. External
      exposure is determined by chemical analysis of the chemicals in food, water or
      air. The more relevant internal exposure is assessed by analysis of the chemical
      or its metabolites in body fluids and, if appropriate, by protein- or DNA
      adducts. Effects are monitored by determining the relevant organ-specific
      parameters. In the case of genotoxic agents, effect biomonitoring parameters,
      like cytogenetic effects in peripheral blood cells or DNA strand breaks, are
      applied. Genotyping to detect deficiencies in the expression of enzymes, e.g.
      those involved in metabolic activation or inactivation, may explain
      interindividual differences in susceptibility. Overall prospective population
      studies allow exposure monitoring and risk assessment of human exposure only when
      such parameters are included.

PMID- 11323200
TI  - Methodological approaches to the population analysis of toxicity data.
AB  - Toxicokinetics is the assessment of systemic exposure in toxicity studies, in
      which pharmacokinetic data are generated, either as an integral component in the
      conduct of the nonclinical toxicity studies or in specially designed supportive
      studies, in order to assess systemic exposure. The data may be used in the
      interpretation of toxicity findings and contribute to the assessment of the
      relevance of these findings to clinical safety. Data may be obtained from all
      animals in a toxicity study, in representative subgroups, in satellite groups or
      in separate studies. Applying a mixed effects modelling approach in
      toxicokinetics offers many advantages over the current approach of having
      satellite groups. Sparse samples for measuring drug/metabolite concentration are
      collected in all main animals in the majority of studies where toxicological
      findings are obtained. Such sampling is unlikely to distress the animals, disturb
      the conduct of a toxicological study or affect the outcome of the study. Many of
      the outcome measures in toxicological studies are categorical in nature. For
      example, lesions may be scored on a one to four scale, from none to severe. The
      analysis of such data is usually carried out using a general mixed modelling
      approach. We have implemented such models in a nonlinear mixed effects modelling
      framework which allows us to relate pharmacokinetic response to outcome. A case
      study is used to illustrate the principles of general mixed effects modelling in
      toxicokinetics.

PMID- 11323201
TI  - Modelling and simulation of variability and uncertainty in toxicokinetics and
      pharmacokinetics.
AB  - Two important methodological issues within the framework of the variability and
      uncertainty analysis of toxicokinetic and pharmacokinetic systems are discussed:
      (i) modelling and simulation of the existing physiologic variability in a
      population; and (ii) modelling and simulation of variability and uncertainty when
      there is insufficient or not well defined (e.g. small sample, semiquantitative,
      qualitative and vague) information available. Physiologically based
      pharmacokinetic models are especially suited for separating and characterising
      the physiologic variability from the overall variability and uncertainty in the
      system. Monte Carlo sampling should draw from multivariate distributions, which
      reflect all levels of existing dependencies in the intact organism. The
      population characteristics should be taken into account. A fuzzy simulation
      approach is proposed to model variability and uncertainty when there is
      semiquantitative, qualitative and vague information about the model parameters
      and their statistical distributions cannot be defined reliably.

PMID- 11323203
TI  - Genetic parameter estimates for pre-weaning weight traits in Dorper sheep.
AB  - Genetic parameters were estimated for birth-, 42-day, and 100-day (weaning)
      weight in the Dorper flock of the Glen Agricultural Institute in South Africa.
      Direct heritability estimates of 0.11, 0.28 and 0.20 and maternal heritability
      estimates of 0.10, 0.10 and 0.10 were obtained for body weights at birth, 42 and
      100 days, respectively. The corresponding genetic correlation estimates between
      direct and maternal effects were 0.35, -0.63 and -0.58, respectively. Both direct
      and maternal genetic correlation estimates among the traits were of moderate to
      high magnitude and positive. It is concluded that the traits can be improved by
      selection with no serious antagonisms among traits studied.

PMID- 11323204
TI  - Determinants of short-run supply of small ruminants in Botswana.
AB  - This study utilizes pooled agricultural region data for the 1982-1987 period to
      estimate the short-run supply of sheep and goats in Botswana. Elasticity
      estimates indicate that a 1% increase (decrease) in rainfall at year t leads to a
      0.53% rise (fall) in goat marketing in year t+1, and that a 1% rise (fall) in
      goat population (inventory) leads to a 0.15% rise (fall) in goat sales. The sheep
      equation reveals that a 1% increase (decrease) in sheep inventory results in a
      1.23% rise (fall) in the number of sheep marketed, and suggests that rainfall has
      no impact on sheep sales. It is argued that the inelastic response of goat sales
      to changes in goat inventory reinforces the general view that livestock in
      Botswana are treated as a store of wealth, rather than as primarily a commercial
      activity for generating cash incomes. This tendency seems to be reduced in the
      case of sheep, where an elastic response of sales to changes in sheep inventory
      is observed. Producer prices are found to have no impact on small ruminant sale.
      The lack of responsiveness of supply to prices may be revealing the existence of
      inadequate access by most producers to organized markets for small ruminants. It
      is further argued that without promoting the development of such markets, other
      developmental efforts, particularly those geared at improving farm-level
      productivity will yield no positive outcomes, as farmers lack the cash incentive
      to invest in improved management and husbandry practices.

PMID- 11323205
TI  - Comparison of two surgical techniques for mastectomy of goats.
AB  - Two different techniques for mastectomy were carried out on 14 goats with
      gangrenous mastitis. The animals were randomly assigned to one of two groups
      containing seven goats each. The first group was operated via a classical
      surgical mastectomy technique (either bilateral (n=5) or unilateral (n=2)). The
      second group was operated via vascular ligation of the external pudendal blood
      vessels and milk vein and amputation of the affected teat (either bilateral (n=3)
      or unilateral (n=4)). Comparison between the two groups was carried out. Vascular
      ligation and teat amputation proved to be an effective, quick, safe, and less
      expensive technique for mastectomy in goats. Ligation of udder vasculature was
      less traumatic than surgical amputation and the stress on the patient was
      minimal.

PMID- 11323206
TI  - Production and characterisation of monoclonal antibodies to an Indian isolate of
      peste des petits ruminants virus.
AB  - Nine monoclonal antibodies (Mabs) were produced against an Indian isolate of
      peste des petits ruminants (PPR) virus. These Mabs were directed against the
      nucleo (N) protein and were of IgG1 isotype. The Mabs produced intranuclear or
      coarse granular cytoplasmic fluorescence in PPR virus infected Vero cells and did
      not exhibit any neutralising activity. The Mabs cross-reacted with five other
      local isolates of PPR virus in slot blot hybridisation, radio immunoprecipitation
      assay (RIPA) and fixed-cell enzyme linked immunosorbent assay (ELISA). Two of the
      nine Mabs cross-reacted mildly with the vaccine strain of rinderpest (RP) virus
      in slot blot hybridisation and fixed-cell ELISA but did not precipitate the N
      protein of RP virus in RIPA. The N protein specific Mabs will be highly useful in
      differential diagnosis of PPR from RP.

PMID- 11323207
TI  - Prevalence of coccidia and gastrointestinal nematode infections in cross bred
      goats in the dry areas of Sri Lanka.
AB  - The prevalence and intensity of oocysts of coccidia, particularly Eimeria
      species, and eggs of gastrointestinal nematodes in kids (2-4 months), young goats
      (5-12 months) and adult goats (>1 year) were determined in five large herds
      managed extensively in five villages in the dry zone. Of the representative
      samples examined, oocysts were found in 88% of kids, 91% of young goats and 83%
      of adults. Seven species of Eimeria were identified in faecal samples by salt
      flotation. Eimeria ninakohlyakimovae (31%), E. alijevi (29%) and E. arloingi
      (21%) were the most common species in all age categories. Other species
      encountered were E. christenseni (7%), E. jolchijevi (6%), E. hirchi (3%) and E.
      aspheronica (1%). Gastrointestinal nematode eggs were found in 89% of the kids,
      94% of the young goats and 84% of the adult goats. Identification of
      gastrointestinal nematodes revealed Haemonchus contortus (90%) followed by
      Oesophogostomum spp. (8.5%) and Trichostrongylus spp. (1%) in all three age
      categories examined. Both Eimeria and gastrointestinal nematodes were found in
      77% of the kids, 86% of the young goats and 71% of adult goats. The mean oocyst
      counts per gram of faeces in kids, young goats and adult goats were 9728, 1946,
      and 2667, respectively. The oocyst counts were not different significantly
      between age groups (P>0.05). The mean egg counts per gram of faeces in kids,
      young goats and adult goats were 1217, 1641 and 1092, respectively. The egg
      counts in kids were significantly lower than that in young goats (P<0.05). The
      intensity of Eimeria and gastrointestinal nematode infections between herds were
      significantly different (P<0.01).

PMID- 11323208
TI  - Response of Najdi sheep to oral administration of Citrullus colocynthis fruits,
      Nerium oleander leaves or their mixture.
AB  - Susceptibility of sheep to oral administration of Citrullus colocynthis fruits,
      Nerium oleander leaves or their mixture is described in 12 sheep assigned as
      untreated controls, C. colocynthis-treated at 0.25g/kg/day, N. oleander-treated
      at 0.25g/kg and plant mixture-treated at 0.25g of C. colocynthis/kg plus 0.25g of
      N. oleander/kg. The daily use of 0.25g of C. colocynthis/kg for 42 days was not
      fatal to sheep and caused slight diarrhoea, catarrhal enteritis, centrilobular
      hepatocellular fatty change and degeneration of the renal tubular cells. Single
      oral doses of 0.25g of N. oleander/kg were lethal to sheep within 18-24h and
      caused uneasiness, grinding of the teeth, dyspnoea, anorexia, frequent urination,
      ruminal bloat, ataxia and recumbency before death. The main lesions were
      widespread congestion and haemorrhage, pulmonary cyanosis and emphysema and
      severe hepatonephropathy. Rapid death was also observed in sheep receiving single
      doses of the mixture of the two plants. Effects were correlated with changes in
      the activities of serum lactic dehydrogenase (LDH) and aspartate transaminase
      (AST) and concentrations of cholesterol, bilirubin, total protein, albumin,
      globulin and urea and haematological parameters.

PMID- 11323209
TI  - Relationships among somatic cell count, California mastitis test, impedance and
      bacteriological status of milk in goats and sheep in early lactation.
AB  - The objectives of this trial were to evaluate and compare the test
      characteristics of a number of indirect tests of bacteriological status of the
      milk from goats and sheep and to assess the affect of varying levels of
      prevalence of infection on the performance of those tests.The somatic cell count,
      California mastitis test (CMT) score, electrical impedance and the
      bacteriological status of 220 and 262 milk samples from the glands of lactating
      dairy goats and sheep, respectively, were determined. The sensitivity and
      specificity of indirect tests in predicting the bacteriological status were
      compared by analyzing the areas under the receiver operating characteristic curve
      and calculating the likelihood ratio at various cut-off values.Bacteria were
      isolated from 17.7 and 4.6% of glands from goats and sheep, respectively. Somatic
      cell count was a better predictor of bacteriological status than either the CMT
      score or impedance in both goats and sheep. However, knowledge of the CMT score
      in both sheep and goats and the impedance in goats increases the likelihood of
      predicting the presence of a bacterial pathogen compared to no testing at all
      (P<0.05). Knowledge of the age and days postpartum of the animals at the time of
      testing did not increase the probability that infection status could be
      predicted. Variation in cut-off levels to predict infection status reported in
      the literature may be due to variation in the prevalence of infection in the
      populations studied. Use of likelihood ratio allows comparison of tests over a
      range of prevalence's as likelihood ratios are independent of prevalence. The
      prevalence of infection within a herd should be considered when selecting a cut
      off value for indirect testing for the presence of bacteria in milk of small
      ruminants.

PMID- 11323210
TI  - Nutritive value of lentil and vetch straws as compared with alfalfa hay and wheat
      straw for replacement ewe lambs.
AB  - The objective of this study was to compare the nutritive value of lentil straw
      (LS) and vetch straws (VS) with alfalfa hay (AH) and wheat straw (WS). Forty
      Awassi ewes (body weight (BW)=56.2kg) were assigned randomly to four dietary
      treatments (10 ewes per treatment) for 6 weeks using a complete randomize design.
      In each dietary treatment, ewes were fed 550g per day of concentrate mix
      formulated to supply 40% of the metabolizable energy requirement. After the
      consumption of the concentrate mix, ewes had ad libtum access to AH, LS, VS, or
      WS. Forage intake, total dry matter intake (DMI), and organic matter intake (OMI)
      were higher for AH and LS and lowest for WS. Final weight of ewes fed AH and LS
      diets were higher (P<0.05) than VS and WS diets. However, ewes fed VS diet gained
      more weight (2.5kg) than ewes on WS diet (0.2kg). Dry matter digestibility was
      higher for the AH and LS diets (59.4%), and lowest for WS diet (49.6%). The VS
      diet had an intermediate value (54.4%). Ruminal passage rate was higher for AH
      and LS (3.4% per hour) compared with WS (1.9% per hour). Eating time for the AH
      diet was lowest compared with the rest of the forages. Eating time, expressed as
      minutes per kilogram NDF intake, was highest for WS and VS diets (680min)
      compared with AH and LS diets (535min). WS diet required more time for rumination
      (395min per day) compared to AH, LS, and VS diets. However, ewes on VS diet spent
      more time ruminating per kilogram NDF consumed (954min) compared with WS, LS, and
      AH diets (901, 617, and 597min, respectively). These results were significant and
      demonstrate that the nutritive value of LS is greater than VS and close to the
      nutritive value of AH. VS nutritive value is slightly greater than WS.

PMID- 11323211
TI  - Nutritive value of maize stover/pasture legume mixtures as dry season
      supplementation for sheep.
AB  - Two experiments were carried out to determine the nutrient contents and relative
      preferences of maize stover and three legumes forages and their feeding on intake
      and digestibility of sheep. Maize stover was blended with three legumes, stylo
      (Stylosanthes guainensis), siratro (Macroptilium atropurpureum) and centro
      (Centrocema pubescens), to produce four treatments, namely, only maize stover
      (control), stover/stylo, stover/siratro and stover/centro mixtures. The first
      experiment evaluated the relative preference of the stover and the various
      stover/legume mixtures when offered to sheep. Six rams were offered pair
      combinations of the treatments in a 6x6 Latin square with a split plot
      arrangement such that each ram had access to two feeds at a time in each period
      of 6 days. The second experiment included measurements of intake and
      digestibility of the stover and stover/legume mixtures. Four intact and four
      castrated male sheep were used in two, 4x4 Latin squares with 21-day periods. The
      least (P<0.05) preferred feed was maize stover when it was offered as the sole
      feed. There were no significant differences in preference among the stover/legume
      mixtures. Dry matter intake (DMI) was highest (P<0.05) when sheep were offered
      the stover/centro mixture and lowest (P<0.05) when maize stover was fed as the
      sole feed. Dry matter digestibility did not differ significantly among
      treatments. Sheep that were offered maize stover only lost weight, those fed
      stover/centro gained weight and those that were fed either stover/siratro or
      stover/stylo maintained weight. However, these short-term weight changes may
      reflect changes in fill as much as changes in body tissue. Addition of legumes to
      maize stover improved the nutritive value, possibly by increasing the nitrogen
      content of the stover. The results suggest that maize stover, which is normally
      left to rot in the field, could be better utilised by intercropping with legumes
      and allowing animals access after grain harvest.

PMID- 11323212
TI  - Changes in some blood constituents of Barki ewes during pregnancy and lactation
      under semi arid conditions.
AB  - A study based on 12 pregnant and six dry Barki ewes was carried out to examine
      the changes in blood constituents during pregnancy and lactation periods. The
      blood parameters were blood hemoglobin, packed cell volume percent (PCV%), mean
      corpuscular hemoglobin concentration (MCHC), glucose, aspartate aminotransaminase
      (AST or GOT), alanine aminotransaminase (ALT or GPT), total plasma protein,
      albumin, globulin, albumin to globulin ratio (A/G), urea and creatinine. During
      pregnancy all these parameters started to increase significantly, but in
      different stages, reaching maximum values at parturition. In contrast, dry ewes
      showed almost stable values during the experimental period. From 10th week to
      parturition, PCV% and MCHC increased (P<0.01) in pregnant ewes, which resulted in
      increased (P<0.01) blood hemoglobin. Blood glucose increased from the 4th week of
      pregnancy to reach its maximum at parturition (60.15-90.08mg/dl). The two
      transaminases increased significantly from the 2nd week (52.23-65.02IU for AST
      and 8.02-15.12IU for ALT). Plasma protein with its two components, albumin and
      globulin, increased significantly at the 6th week, but dropped throughout the 16
      18th week of pregnancy. Urea and creatinine began to increase significantly after
      10-12 weeks of pregnancy (from 54.73 to 72.11mg/dl for urea and from 0.882 to
      2.475mg/dl for creatinine). During the first month of lactation, PCV decreased
      sharply in lactating ewes and was significantly lower than in dry ewes at the 3rd
      week of lactation (24.25 versus 27.17%), which resulted in a drop in blood
      hemoglobin at the 4th week (68.42 versus 74.00g/l). However, lactating ewes
      maintained significantly higher values of MCHC (30.01-31.19% for lactating versus
      29.87-27.48% for dry). In lactating ewes, levels of glucose, ALT, urea and
      creatinine returned to levels comparable to those in dry ewes. The same occurred
      with total plasma proteins, mainly due to a sharp decrease in globulin, while
      albumin remained higher than in dry ewes with a slow decline, which resulted in
      higher values of A/G ratio during lactation. Aspartate aminotransferase remained
      higher than in dry ewes.

PMID- 11323213
TI  - Expression of apoptosis-related proteins in mammary gland of goat.
AB  - The expression of apoptosis-related proteins: TGF-beta1 (auto/paracrine inducer)
      and its receptor (TGF-betaRIII), Bax (promoter), Bcl-2 (inhibitor) and CPP-32
      (executor of apoptosis) as well as the apoptotic cell number in mammary glands of
      11 Polish White Improved goats in the course of the lactation cycle (peak of
      lactation: days 40-70, late lactation: days 208-256, drying off: days 267-340)
      was investigated. The immunohistochemical study demonstrated a significant
      increase in TGF-beta1 and TGF-betaRIII expression in the lobuloalveolar tissue
      from the early lactation to the dry period. Our recent study on HC11 mouse
      mammary epithelial cells [Cell. Mol. Biol. 46 (2000) 175] has revealed an
      inhibitory effect of prolactin on TGF-beta1 transcription, which may explain the
      low TGF-beta1 synthesis during lactogenesis and galactopoiesis and the increase
      in TGF-beta1 and TGF-betaIIIR expression in late lactation and dry period. Bax
      expression was the lowest in the peak of lactation, significantly increased in
      late lactation and remained elevated during drying off. Bcl-2 content was lower
      than Bax in all examined periods, but it increased significantly at the end of
      lactation, which suggests the survival of cells with the highest resistance to
      apoptogenic stimuli. The increase in Bcl-2 level in remnant lobuloalveolar tissue
      is probably the molecular mechanism that limits the rate of secretory tissue
      involution. The induction of CPP-32 (caspase 3) from the peak of lactation to dry
      period was accompanied by a progressive loss of mammary epithelial cells and the
      increase in apoptotic cell numbers but only in the dry period. The increase in
      the expression of examined proteins in the late lactation and the dry period
      indicates their involvement in the induction (TGF-beta1 and TGF-betaRIII),
      regulation (Bax and Bcl-2) and execution (CPP-32) of programmed cell death in the
      course of mammary gland involution. The lack of an increase in apoptotic cell
      number in late lactation, in spite of the evident decrease in total cell number,
      suggests milk as an alternative route (apart from phagocytosis) of apoptotic
      cells elimination from the mammary gland. The presented results provide new
      insights into the molecular mechanism of mammary cell apoptosis in goat and for
      this reason may have practical implications for control and regulation of mammary
      gland remodelling, which is a prerequisite for subsequent successful lactation.

PMID- 11323214
TI  - Pen confinement of yearling ewes with cows or heifers for 14 days to produce
      bonded sheep.
AB  - Mixed species stocking is commonly a more ecologically sound and efficient use of
      forage resources than single species stocking, especially in pastures having
      complex assemblages of forage species. However, in many environments livestock
      predation on especially smaller ruminants adds an extra challenge to mixed
      species stocking. When mixed sheep and cattle remain consistently as a cohesive
      group (flerd), predation risks are lessened, while fencing and herding costs are
      reduced. To establish a cohesive group (bond), a 30-day bonding period in which
      young sheep and cattle pairs are penned together is currently recommended. The
      purpose of this research was to test if a bond could be produced in <30 days (14
      days) using pen confinement; thus reducing feed, labor, and overhead costs.
      Additionally, we tested whether cow age affects cohesiveness of bonded pairs
      immediately following 14 days of pen confinement. Sixteen mature cows (7-8 years
      of age) and sixteen 9-month-old heifers were randomly paired with one of 32
      yearling ewe lambs. Eight cow/ewe (PC) and eight heifer/ewe (PH) pairs were
      maintained individually in 2mx6m pens for 14 days. The other eight-cow/ewe (NC)
      and heifer/ewe (NH) pairs were separated by species with each species maintained
      on separate pastures for the 14-day period. After 14 days, pairs were released in
      observation paddocks and separation distance between treatment pairs was measured
      during a 30-min open field test. Other behaviors were also noted and recorded
      during the field test. Separation distance did not differ (P=0.973) between the
      PC and PH treatments; however, separation distance for NC versus NH (P<0.004), NC
      versus PC (P<0.001), and NH versus PH (P<0.002) all differed. Mean separation
      distance (meters) and standard errors were 40+/-3.9, 3+/-0.3, 76+/-5.3, and 4+/
      1.4 for NH, PH, NC, and PC treatments, respectively. Overall, the animals that
      were penned spent more time grazing and less time walking than animals not
      previously penned for 14 days. Penned animals also vocalized less than non-penned
      animals during the open field test. The bond sheep formed to the bovines was not
      affected by cow age. These data suggest that inter-specific bond formation using
      pen confinement can be accomplished within 14 days, representing a 53% savings in
      time and associated costs when compared to pen confinement lasting 30 days.

PMID- 11323215
TI  - Recent advances in melanoma research.
AB  - Recent advancement in the research of malignant melanoma is reviewed. Among many
      gene alterations detected in human melanoma, defect of CDKN2A located at
      chromosome 9p21 seems to be most important in the earlier developmental phase,
      though significance of this gene in the evolution of melanoma in situ has not
      been confirmed yet. Deletions of PTEN/MMAC1 on 10q23.3 and AIM1 on 6q21 as well
      as mutations of ras gene are involved in the later progression stages of
      melanoma. Adhesion molecules relevant to development and progression of melanoma
      have been intensely investigated in recent years, revealing crucial roles of
      cadherins and alpha(v)beta(3) integrin in the biologic behaviors of melanoma
      cells. Melanoma is characterized by extremely high potential of developing
      metastases. Dynamic changes of matrix metalloproteinase activity during invasion
      and movement of melanoma cells may be a major concern in this field. Fragility of
      blood vessels in melanoma lesions is another important point related to
      hematogeneous metastases. Acral lentiginous melanoma is a unique subtype of
      melanoma, because, in contrast to other subtypes, ultraviolet irradiation is not
      a major factor in its development. Investigation of pathogenesis of acral
      lentiginous melanoma surely provides us with new information about mechanism of
      melanocyte transformation. Recent advances in the management of malignant
      melanoma are also briefly reviewed, such as biochemotherapy, immunotherapy, and
      gene therapy. Finally, the concept of molecular classification of melanoma by
      gene expression profile is introduced, which possibly enables us to give the
      tailor-made therapy for each melanoma patient in the near future.

PMID- 11323217
TI  - Induction of CD54 and CD58 expression in cultured human endothelial cells by beta
      interferon with or without hyperthermia in vitro.
AB  - Human endothelial cells were treated by beta-interferon with or without
      hyperthermia at 42 degrees C for 90 min in vitro to investigate whether these
      modalities were able to increase the expression of either CD54 or CD58 on the
      surface of the endothelial cells. The results were that the population of the
      endothelial cells expressing both CD54 and CD58 increased 4 days after the
      treatment with beta-interferon, which was independent of hyperthermia. In
      contrast, the primarily isolated peripheral lymphocytes from a patient with
      malignant melanoma (disease free state) or normal individuals responded to
      neither beta-interferon nor hyperthermia in terms of the expression of CD54 or
      CD58. These results indicate that beta-interferon may activate endothelial cells
      to lead to the successive activation of the other immune cells in vivo.

PMID- 11323216
TI  - Clinical significance of enzyme-linked immunosorbent assay for the detection of
      circulating anti-BP180 autoantibodies in patients with bullous pemphigoid.
AB  - The NC16A domain of the 180-kDa bullous pemphigoid antigen (BP180) is the most
      immunogenic and, probably, pathogenic region in bullous pemphigoid (BP). In the
      present study, in order to determine whether serum level of circulating anti
      BP180 autoantibodies is a valuable serum marker in BP, the immunoreactivity of
      sera against the NC16A domain of BP180 was measured using enzyme-linked
      immunosorbent assay (ELISA) in ten patients with BP. Serum levels of anti-BP180
      autoantibodies correlated with the clinical course in BP patients, who received
      various therapeutic agents. The result suggests that this NC16A-ELISA is a useful
      method for evaluating the clinical course and efficacy of the therapy in patients
      with BP.

PMID- 11323218
TI  - Clinical characteristics of mite allergen specific-lymphocytes stimulation test
      positive Japanese cases with adult type atopic dermatitis.
AB  - To identify the correlation between the house dust mite-specific lymphocytes
      proliferation and other clinical parameters and clinical features, we conducted a
      lymphocytes stimulation test in 37 patients with atopic dermatitis. A total of 12
      patients showed positive reactions (positive patients) and 25 showed no reaction
      (negative patients). Both the number and percentage of peripheral blood
      eosinophils were significantly lower in positive patients than in negative
      patients. Stimulation index measured by lymphocytes stimulation test showed no
      correlation with the total IgE level, nor the number and percentage of
      eosinophils. Stimulation index weakly correlated with mite-specific IgE-RAST
      scores both in positive patients and in negative patients. Only in positive
      patients, stimulation index weakly correlated with the severity measured by the
      clinician score method. Three out of four positive patients showed an increased
      stimulation index in accordance with increased clinician scores during their
      clinical course. These results could suggest that, in positive patients, a house
      dust mite allergy might be an active cause that exacerbates clinical symptoms at
      the time of their clinical course. Therefore, the stimulation index of the
      lymphocytes stimulation test might become one of the effective parameters that
      reflect the involvement of a house dust mite allergy in adult atopic patients.

PMID- 11323219
TI  - Early mycosis fungoides: molecular analysis for its diagnosis and the absence of
      p53 gene mutations in cases with progression.
AB  - The histological diagnosis of initial mycosis fungoides (MF) and the molecular
      mechanisms that are responsible for its progression and transformation to the
      more highly malignant variants of MF remain largely unknown. Because of the rare
      occurrence of these tumours, the need for snap frozen skin biopsy specimens and
      the difficulty to obtain suitable material for karyotypic and genotypic analysis,
      specific cytogenetic and molecular lesions have not yet been identified. In
      particular the role of known oncogenes and tumour suppressor genes, including the
      p53 gene, in the pathogenesis and clinical progression of MF has not been
      extensively investigated. The present study was carried out using the polymerase
      chain reaction (PCR) technique combined with temperature gradient gel
      electrophoresis (TGGE) to detect mutations of the p53 gene in 58 patients with
      MF. TGGE analysis was also used in combination with clonality analysis by means
      of T-cell receptor gamma (TCRG) gene rearrangement studies to distinguish
      parapsoriasis en plaque and initial MF from patch/plaque stage MF. More than 83%
      of the diagnoses of initial MF could be confirmed using PCR-TGGE analysis.
      However, although the sensitive TGGE analysis was used for all exons, p53 gene
      polymorphisms were found in 4 and p53 gene mutation in only 1 of 58 biopsy
      specimens. It appears unlikely that p53 gene mutations play a role in either the
      pathogenesis of parapsoriasis and initial MF or their progression to advanced
      stages of MF. However, TCRG gene rearrangement studies by means of TCR-TGGE
      analysis may be useful for distinguishing histologically discordant cases of
      initial MF.

PMID- 11323220
TI  - IL-10 augments the IFN-gamma and TNF-alpha induced TARC production in HaCaT
      cells: a possible mechanism in the inflammatory reaction of atopic dermatitis.
AB  - The CC-chemokine TARC is known to be a ligand for the CCR4 receptor which in turn
      is known to be expressed selectively on the Th(2)-subset of lymphocytes. Atopic
      dermatitis is generally believed to be a Th(2)-type disease, and TARC has been
      shown to be expressed in the skin lesions of a murine model of AD. IL-10 is an
      interleukine generally known for its ability to inhibit cytokine production,
      however it has been found to be highly expressed in the skin from AD patients. We
      show in this report that IL-10 is able to augment the TARC inducing effects of
      TNFalpha and IFNgamma in HaCaT cells, a property that may be important in the
      determination of the composition of the cells of the inflammation in the skin of
      AD patients. In addition, we show that the IL10 agonist IT 9302, a nona-peptide
      from the carboxylic end of IL-10, has the same effect on TARC production from
      HaCaT cells.

PMID- 11323221
TI  - Predominant IgG4 subclass in autoantibodies of pemphigus vulgaris and foliaceus.
AB  - Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are autoimmune skin diseases
      caused by autoantibodies against desmoglein (Dsg) 3 and Dsg1. We have previously
      developed ELISAs using recombinant Dsg3 and Dsg1 expressed by baculovirus as a
      diagnostic tool for pemphigus. In this study, we determined the frequency of
      coexistence of IgA class as well as distribution of IgG subclass. Two out of 49
      PV and PF sera tested had anti-Dsg1 IgA in addition to anti-Dsg1 IgG.
      Interestingly, one of them showed prominent pustular formation. Among IgG
      subclass, IgG4 was predominant and found in all of the 30 PV and 19 PF sera
      tested, followed by IgG1, detected in 25 out of 30 PV and 12 out of 19 PF sera.
      Even though IgG2 and IgG3 were detected in 13 and one PV and 6 and 4 PF sera,
      respectively, the ELISA titers had barely exceeded the cutoff value in most of
      the cases. There was no IgG subclass shift during the course of the disease in
      seven cases examined. These findings indicate that IgG4 subclass is the
      predominant autoantibodies in both PV and PF, while IgG1 is also frequently
      found.

PMID- 11323222
TI  - Levels of beta-endorphin in the plasma and skin tissue fluids of patients with
      vitiligo.
AB  - In order to study the possible role of beta-endorphin in the pathogenesis of
      vitiligo, the authors measured the levels of beta-endorphin in the plasma from 40
      patients and the tissue fluids of skin lesions and uninvolved skin from 33
      patients with vitiligo, using a 125I RIA kit. The results showed that the levels
      of plasma beta-endorphin in the patients with vitiligo of all of the generalized,
      focal and segmental types and in either progressive and stable stages were
      significantly higher then the normal controls. The levels of beta-endorphin in
      the tissue fluids from skin lesions were significantly higher than those from
      uninvolved skin in both the local type and segmental type. In the generalized
      type, the levels of beta-endorphin were obviously increased in both the tissue
      fluids from skin lesions and those from uninvolved skin. It seems that beta
      endorphin plays a role in the pathogenesis of vitiligo.

PMID- 11323223
TI  - Abnormal NF-kappaB signaling pathway with enhanced susceptibility to apoptosis in
      immortalized keratinocytes.
AB  - The transcriptional activation and proper regulation of NF-kappaB is known to be
      important to the apoptotic resistant phenotype of epidermal-derived
      keratinocytes. By comparing and contrasting the responses of normal foreskin
      derived keratinocytes versus an immortalized skin-derived keratinocyte cell line
      (i.e. HaCaT cells), several molecular defects involving NF-kappaB signaling
      pathway were delineated in the immortalized keratinocytes. While exposure to IFN
      gamma plus TPA produces growth arrest in both normal and immortalized
      keratinocytes, with rapid phosphorylation of MEKKI and recruitment of distinctive
      protein kinase C isoforms into the signalosome complex, subsequent molecular
      events necessary for NF-kappaB activation were abnormal in HaCaT cells. This
      disrupted NF-kappaB activation in HaCaT cells was accompanied by enhanced
      susceptibility to UV-light induced apoptosis, which was associated with elevated
      levels of E2F-1 and decreased TRAF1/TRAF2 levels. Additional defects in HaCaT
      cells included markedly diminished levels of IKKbeta (and lack of induction of
      kinase activity) in response to inflammatory stimuli, a failure of p21(WAF1/CIP1)
      to associate with CDK2, and a decreased association between p65 and p300. These
      studies suggest caution in using HaCaT cells as a substitute for normal
      keratinocytes to study apoptosis in the skin. Thus, it appears that while the
      immortalized cells can escape cell cycle checkpoints by elevated levels of E2F-1,
      an adverse biological consequence of such dysregulated cell cycle control is the
      inability to activate the anti-apoptotic NF-kappaB signaling pathway. Therefore,
      exploiting this apoptosis vulnerability in pre-malignant, or immortalized cells,
      prior to acquiring a death-defying phenotype characteristic of more advanced
      malignant cell types, provides the basis for an early interventional therapeutic
      strategy for cutaneous oncologists.

PMID- 11323224
TI  - Serum eosinophil derived neurotoxin may reflect more strongly disease severity in
      childhood atopic dermatitis than eosinophil cationic protein.
AB  - Serum levels of eosinophil cationic protein (ECP) have been shown to be a good
      parameter of the disease severity of patients with atopic dermatitis (AD).
      However, the relationship between the disease severity and the eosinophil derived
      neurotoxin (EDN) has not been established in AD patients. The purpose of this
      study is to examine serum ECP and EDN levels in relation to the disease severity
      in AD children. Serum ECP and EDN levels were assessed in relation to the skin
      scores in 34 AD children (18 boys and 16 girls; age 0.6 to 7years: mean+/-S.D.
      2.2+/-1.9) and six non-atopic control children (three boys and three girls; age 1
      to 3years: mean+/-S.D. 1.7+/-0.9). Serum ECP and EDN levels of the patients with
      AD were significantly increased compared with the non-atopic controls. Serum EDN
      levels of the patients were also related to the disease severity. The skin scores
      were more significantly correlated with serum EDN levels than ECP levels. We
      concluded that serum EDN may reflect more strongly disease severity as
      eosinophilic activation in AD children than serum ECP.

PMID- 11323225
TI  - Enhancing the ability of gait analyses to differentiate between groups: scaling
      gait data to body size.
AB  - One goal of gait analysis is to distinguish clearly between a set of abnormal
      gait values measured from a patient referenced to a comparable population.
      However, the comparable population is often composed of individuals of various
      heights and weights, which increases inter-subject gait value variation which
      reduces the ability of a statistical test to identify a set of gait data outcomes
      with evaluative properties. Therefore, scaling gait data, based on subject leg
      length and mass, is commonly used to decrease the inter-subject variation but the
      efficacy of these methods is unknown. In this paper each of eight scaling
      strategies (none, ad hoc, dimensionless numbers, and five connected strategies
      based on similarity, dimensional analysis and muscle properties) were used to
      modify a set of gait data outcomes acquired from 10 individuals spanning a wide
      range of height (1.33-1.96 m) and mass (42.3-148.8 kg). These data were then
      examined to select that strategy and those scaling factors which maximally
      reduced inter-subject variation. The ad hoc, dimensionless numbers, and
      dynamic/mechanical/elastic (diameter of a limb (D) proportional to it's length
      (L) to the 1.5 power; time proportional to L(2) D(-1)) scaling strategies reduced
      the global inter-subject gait data outcome variation to 44% of its un-scaled
      value. Considering ten commonly reported gait data outcomes (temporal and spatial
      (stride time, stride length, progression velocity), kinematic (angles in the
      sagittal and frontal planes, angles in the transverse plane), external kinetic
      (ground reaction force and moment), and internal kinetic (joint force, moment,
      and power)) these three scaling strategies provided the largest number of minimum
      inter-subject variations (10, 10, and 9, respectively). Reduced inter-subject
      variation in gait data outcomes increases the ability of a statistical tool to
      detect a difference between a patient and a comparable group. With a
      statistically significant difference a clinician can then decide if this
      patient's gait pattern clinically deviates from that of the comparable group and
      an appropriate intervention warranted. The ad hoc, dimensionless numbers, and the
      dynamic/mechanical/elastic scaling strategies all reduce maximally the inter
      subject variation in gait data outcomes.

PMID- 11323226
TI  - Reducing the variability of oxygen consumption measurements.
AB  - The oxygen consumption (O(2)) of 10 able-bodied adults each walking at a variety
      of cadences and hence speeds was measured. The effect on variability of
      subtracting the resting oxygen rate from gross measurements and of normalising
      walking speed to the subject's height was investigated. Both of these were indeed
      found to reduce variability. A total reduction of more than 40% in the
      variability of O(2) cost measurements was observed. Using these techniques it was
      found that, at walking speeds below the average, nett O(2) cost per height was
      very nearly independent of walking speed.

PMID- 11323227
TI  - Intralimb coordination following obstacle clearance during running: the effect of
      obstacle height.
AB  - The purpose of this study was to investigate the different coordination
      strategies used following obstacle clearance during running. Ten subjects ran
      over a level surface and over obstacles of six different heights (10, 12.5, 15,
      17.5, 20 and 22.5% of their standing height). Analysis based upon the dynamical
      systems theory (DST) was used and the phasing relationships between lower
      extremity segments were examined. The results demonstrated that the increasing
      obstacle height elicited behavioral changes. The foot and the leg became more
      independent in their actions, while the leg and the thigh strengthened their
      already stable relationship. The 15% obstacle height seems to be a critical
      height for the observed changes.

PMID- 11323228
TI  - Effects of shoe sole thickness on joint position sense.
AB  - The objective of this study was to determine the effects of shoe sole thickness
      on joint position sense in the sagittal and frontal plane by determining the
      estimate angle error. Joint position sense was measured by manipulating angle and
      direction of a slope surface board (30 cm x 30 cm x 1.5 cm) to perform the
      movements of dorsiflexion, plantar flexion, inversion and eversion. Sandwiching
      wooden wedges with pre-determined angles between 0 and 25 degrees between the
      slope surface boards made the slope surface angles. Twenty healthy college male
      students were asked to estimate the angle and direction of movements under each
      of the shod conditions while standing on the slope surface board. Estimate angle
      error was calculated for each movement under all shod conditions. For all shod
      conditions, estimate angle error was the greatest for plantar flexion and
      inversion compared to dorsiflexion and eversion. Independent of shod condition,
      subjects had the most difficulty estimating plantar flexion and inversion
      movements.

PMID- 11323230
TI  - (99m)Tc-HYNIC-derivatized ternary ligand complexes for (99m)Tc-labeled
      polypeptides with low in vivo protein binding.
AB  - 6-Hydrazinopyridine-3-carboxylic acid (HYNIC) is a representative agent used to
      prepare technetium-99m ((99m)Tc)-labeled polypeptides with tricine as a coligand.
      However, (99m)Tc-HYNIC-labeled polypeptides show delayed elimination rates of the
      radioactivity not only from the blood but also from nontarget tissues such as the
      liver and kidney. In this study, a preformed chelate of tetrafluorophenol (TFP)
      active ester of [(99m)Tc](HYNIC)(tricine)(benzoylpyridine: BP) ternary complex
      was synthesized to prepare (99m)Tc-labeled polypeptides with higher stability
      against exchange reactions with proteins in plasma and lysosomes using the Fab
      fragment of a monoclonal antibody and galactosyl-neoglycoalbumin (NGA) as model
      polypeptides. When incubated in plasma, [(99m)Tc](HYNIC-Fab)(tricine)(BP) showed
      significant reduction of the radioactivity in high molecular weight fractions
      compared with [(99m)Tc](HYNIC-Fab)(tricine)(2.) When injected into mice,
      [(99m)Tc](HYNIC-NGA)(tricine)(BP) was metabolized to [(99m)Tc](HYNIC
      lysine)(tricine)(BP) in the liver with no radioactivity detected in protein-bound
      fractions in contrast to the observations with [(99m)Tc](HYNIC-NGA)(tricine)(2.)
      In addition, [(99m)Tc](HYNIC-NGA)(tricine)(BP) showed significantly faster
      elimination rates of the radioactivity from the liver as compared with
      [(99m)Tc](HYNIC-NGA)(tricine)(2.) Similar results were observed with (99m)Tc
      labeled Fab fragments where [(99m)Tc](HYNIC-Fab)(tricine)(BP) exhibited
      significantly faster elimination rates of the radioactivity not only from the
      blood but also from the kidney. These findings indicated that conjugation of
      [(99m)Tc](HYNIC)(tricine)(BP) ternary ligand complex to polypeptides accelerated
      elimination rates of the radioactivity from the blood and nontarget tissues due
      to low binding of the [(99m)Tc](HYNIC)(tricine)(BP) complex with proteins in the
      blood and in the lysosomes. Such characteristics would render the TFP active
      ester of [(99m)Tc](HYNIC)(tricine)(BP) complex attractive as a radiolabeling
      reagent for targeted imaging.

PMID- 11323231
TI  - Synthesis and preliminary evaluation of Tc-99m-labeled somatostatin analog (RC
      160) using "3+1" mixed ligand approach.
AB  - The success of (111)In-pentetreotide as a cancer-imaging agent has given impetus
      to the search for other peptide-based radiopharmaceuticals. The labeling with Tc
      99m has become even more attractive because of the ready availability and near
      ideal physical properties. Additionally, the kinetics of the peptide-receptor
      interactions favors the radiolabeling with technetium-99m. A somatostatin analog
      RC-160 has been labeled with Tc-99m using the "3+1" mixed ligand approach
      utilizing the NNS/S coordination sites. The ternary complex was formed in greater
      than 95% within 30 min by simultaneous reduction and complexation of technetium
      99m pertechnetate. The Tc-99m and the surrogate rhenium complexes showed similar
      chromatographic behavior. The complex was evaluated by in vitro receptor binding
      studies carried out on HTB-121 breast cancer cell line and biodistribution
      studies performed in normal mice. Our findings suggest that RC-160 can be labeled
      by the mixed ligand approach with the complex retaining its biological activity
      and warrants further studies.

PMID- 11323232
TI  - Evaluation of potential tracer ability of (99m)Tc-labeled acetylated LDL for
      scintigraphy of LDL-scavenger receptor sites of macrophageal origin.
AB  - Low-density lipoprotein (LDL) receptors are ubiquitously present in a variety of
      human tissues. Scavenger receptors, which are the activated macrophages bearing
      receptors for modified LDL, have been shown to be densely located at the
      atherosclerotic lesions. Acetylated LDL competes with oxidized LDL for access to
      these receptors. The present study was undertaken to optimize (99m)Tc labeling of
      two different forms of LDLs [i.e., native (Na) and acetylated (Ac)] and to
      explore their utility for the scintigraphy of densely localized scavenger LDL
      receptor activity in vivo. Native and acetyl-LDL were labeled with (99m)Tc using
      sodium dithionite as a reducing agent. Significant hepatic and muscular uptake
      precluded optimal availability of (99m)Tc-Ac-LDL in blood, which favors
      macrophageal binding in sterile abscess models in rabbits. (99m)Tc-Ac-LDL behave
      as a novel tracer for imaging densely localized scavenger receptor sites
      constituted by activated macrophages at the site of independent inflammatory
      lesions and appears promising for the scintigraphy of atherosclerotic lesions.

PMID- 11323233
TI  - Surfactant protein B labelled with [(99m)Tc(CO)3(H20)3](+) retains biological
      activity in vitro..
AB  - Labelling of the hydrophobic surfactant protein B (SP-B) under non-reducing
      conditions was achieved with [(99m)Tc(CO)(3)(H2O)(3)](+) prepared according to
      Alberto et al. (JACS, 1998). The binding of radioactivity was protein-specific,
      with an overall radiochemical yield of 50%. Gel electrophoresis and Westernblot
      analyses showed no structural changes of SP-B. Spreading properties and surface
      activity of (99m)Tc-labelled SP-B in an air/water interface coincided with those
      of unlabelled SP-B. (99m)Tc-SP-B seems to be a promising agent to observe
      surfactant spreading under clinical conditions. BACKGROUND: Therapeutic results
      for surfactant instillation in clinical trials are conflicting. The (99m)Tc
      labelling of surfactant would allow to observe its spreading in the lung under
      clinical conditions. METHODS: [(99m)Tc(CO)(3)(H2O)(3)](+) was prepared as
      described by Alberto et al. (JACS, 1998). This carbonyl complex was used for the
      direct labelling of surfactant protein B (SP-B) under non-reductive conditions by
      direct incubation with SP-B at elevated temperature followed by extraction into
      CHCl(3)/MeOH. RESULTS: The hydrophobic protein SP-B was labelled with
      [(99m)Tc(CO)(3)(H2O)(3)](+). An overall radiochemical yield of about 50% was
      achieved. HPLC-analysis revealed a single radiolabelled species according to UV
      elution profile of SP-B, supported by paper and size exclusion chromatography.
      Gel electrophoresis confirmed that the dimer structure of SP-B was preserved.
      Spreading properties of (99m)Tc-labelled SP-B in an air/water interface coincided
      with those of unlabelled SP-B. Spreading of radioactivity observed in a glass
      trough of 26 cm x 27 cm with a gamma camera was completed during the first 7-9
      sec after application of (99m)Tc-labelled SP-B. The corresponding decrease of
      surface tension to 45 mN/m at the peripheral surface tension sensors took 7 sec
      +/- 2 sec (MEAN +/- STD; n = 3). CONCLUSIONS: Direct and specific (99m)Tc
      labelling of the hydrophobic surfactant protein B was achieved using the
      [(99m)Tc(CO)(3)(H2O)(3)](+) precursor. This procedure can easily be used to
      prepare specifically labelled surfactant mixtures with spreading properties that
      coincide with those of unlabelled surfactant.

PMID- 11323234
TI  - Synthesis and evaluation of radiolabeled piperazine derivatives of vesamicol as
      SPECT agents for cholinergic neurons.
AB  - To diagnose and investigate neurodegenerative diseases affecting cholinergic
      neuron density, piperazine derivatives of vesamicol were synthesized and
      evaluated. Previously, we reported that trans-5-iodo-2-hydroxy-3-[4
      phenylpiperazinyl] tetralin (DRC140, 1) possessed high selectivity for vesicular
      acetylcholine transporter (VAChT). In present study of the effect of alkyl
      substituents, we observed that the introduction of a methyl group into the ortho
      or meta positions of the phenyl group of 1 increased affinity for VAChT. trans-5
      Iodo-2-hydroxy-3-[4-[2-methylphenyl] piperazinyl]tetralin (2) displayed high
      affinity and specificity for VAChT. The regional distributions of radioactivity
      in the rat brain correlated well with known patterns of central cholinergic
      innervation. [(123)I]2 is a potentially useful compound for SPECT imaging.

PMID- 11323235
TI  - The potential of radioiodinated (-)-m-iodovesamicol for diagnosing cholinergic
      deficit dementia.
AB  - We investigated changes in the brain distribution of (-)-[(125)I]-m-iodovesamicol
      [(-)-[(125)I]mIV] in cholinergic denervation rats produced by a unilateral lesion
      of the nucleus basalis magnocellularis (NBM). Dual-tracer ex vivo
      autoradiographic analysis using (-)-[(125)I]mIV and [(99m)Tc]HMPAO was conducted
      to the effect of regional cerebral perfusion on the brain distribution of (-)
      [(125)I]mIV in a unilateral NBM-lesioned rat. (-)-[(125)I]mIV binding in the
      ipsilateral cortex to the lesion significantly reduced by 10.4 %, compared with
      that in the contralateral cortex, while (-)-[(125)I]mIV binding in the
      ipsilateral caudate putamen, hippocampus and thalamus did not change. The rate of
      reduction in the (-)-[(125)I]mIV binding (10.4 %) was significantly higher than
      that of [(99m)Tc]HMPAO accumulation (4.0%) in the ipsilateral cortex to the
      lesion (P < 0.01). These results suggested that radioiodinated (-)-mIV may be
      useful in the study of dementia characterized by degeneration of the cholinergic
      neurotransmitter system, such as Alzheimer's disease.

PMID- 11323236
TI  - Synthesis and evaluation of racemic [(11)C]NS2456 and enantiomers as selective
      serotonin reuptake radiotracers for PET.
AB  - Positron emission tomography (PET) radiotracers are needed for quantifying
      serotonin uptake sites in the living brain. Therefore, we evaluated a new
      selective serotonin reuptake inhibitor, NS2456, to determine whether it is suited
      for use in PET. Racemic NS2456 [(1RS,5SR)-8-methyl-3-[4-trifluoromethoxyphenyl]-8
      azabicyclo [3.2.1]oct-2-ene] and its N-demethylated analog, racemic NS2463,
      selectively inhibited serotonin uptake in rat brain synaptosomes; their IC(50)
      values were 3000-fold lower for [(3)H]serotonin than for either [(3)H]dopamine or
      [(3)H]noradrenaline. The enantiomers of NS2463 were also potent inhibitors of
      serotonin uptake in vitro, but they failed to show stereoselectivity. Racemic
      NS2463 as well as its enantiomers were radiolabelled by N-methylation with C-11,
      yielding [(11)C]NS2456 for use in PET of the living porcine brain. The compounds
      crossed the blood-brain barrier rapidly and accumulated preferentially in regions
      rich in serotonin uptake sites (e.g., brainstem, subthalamus and thalamus).
      However, their binding potentials were relatively low and no stereoselectivity
      was found. Thus, neither racemic [(11)C]NS2456 nor its [(11)C]-labelled
      enantiomers are ideal for PET neuroimaging of neuronal serotonin uptake sites.

PMID- 11323238
TI  - Synthesis and preliminary evaluation of a carbon-11-labeled adenosine transporter
      blocker [(11)C]KF21562 .
AB  - We prepared an (11)C-labeled adenosine transporter blocker, [1-methyl-(11)C]-3-[1
      (6,7-dimethoxyquinazolin-4-yl)piperidin-4-yl]-1,6-dimethyl-2,4(1H, 3H)
      quinazolinedione ([(11)C]KF21652) and examined its potential as a positron
      emission tomography (PET) ligand for mapping adenosine transporters in the brain
      and peripheral organs. The log P(7.4) value of KF21652 was 3.14, and the K(i)
      value was 13 nM for adenosine transporters using [(3)H]nitrobenzylthioinosine as
      a radioligand. In mice, the highest initial uptake was found in the liver,
      followed by the kidney and small intestine. The brain uptake was very low. The
      radioactivity level slightly increased with time in the liver and small
      intestine, but decreased in the other organs. Coinjection of carrier KF21652
      slightly decreased the uptake of [(11)C]KF21562 only in the liver, but not in any
      other organs. Ex vivo autoradiography of the rat brain showed that [(11)C]KF21652
      was scarcely incorporated into the brain. On the other hand, in vitro
      autoradiography showed the binding of [(11)C]KF21562 to adenosine transporters
      with high nonspecific binding. These results show that the compound is not a
      suitable PET ligand for mapping adenosine transporters.

PMID- 11323237
TI  - Comparison of [(18)F]altanserin and [(18)F]deuteroaltanserin for PET imaging of
      serotonin(2A) receptors in baboon brain: pharmacological studies.
AB  - The regional distribution in brain, distribution volumes, and pharmacological
      specificity of the PET 5-HT(2A) receptor radiotracer [(18)F]deuteroaltanserin
      were evaluated and compared to those of its non-deuterated derivative
      [(18)F]altanserin. Both radiotracers were administered to baboons by bolus plus
      constant infusion and PET images were acquired up to 8 h. The time-activity
      curves for both tracers stabilized between 4 and 6 h. The ratio of total and free
      parent to metabolites was not significantly different between radiotracers;
      nevertheless, total cortical R(T) (equilibrium ratio of specific to
      nondisplaceable brain uptake) was significantly higher (34-78%) for
      [(18)F]deuteroaltanserin than for [(18)F]altanserin. In contrast, the binding
      potential (Bmax/K(D)) was similar between radiotracers. [(18)F]Deuteroaltanserin
      cortical activity was displaced by the 5-HT(2A) receptor antagonist SR 46349B but
      was not altered by changes in endogenous 5-HT induced by fenfluramine. These
      findings suggest that [(18)F]deuteroaltanserin is essentially equivalent to
      [(18)F]altanserin for 5-HT(2A) receptor imaging in the baboon.

PMID- 11323239
TI  - Whole-body kinetics and dosimetry of cis-4-[(18)F]fluoro-L-proline.
AB  - The whole-body distribution of 4-cis[(18)F]fluoro-L-proline (cis-FPro) was
      studied in six patients with urological tumors by PET. Based on the IMEDOSE and
      MIRDOSE procedures radiation absorbed doses were estimated from whole-body PET
      scans acquired at 1 and 3-5 h after i.v. injection of 400 MBq cis-FPro. Cis-FPro
      showed high retention in the renal cortex and a slight uptake in liver and
      pancreas. Urinary excretion ranged from 12 to 19% at 5 h p.i. Highest absorbed
      doses were found for the urinary bladder wall and the kidneys (44.1/44.0
      microGy/mbq). The effective dose according to ICRP 60 was 15.1 microSv/mbq for
      adults. This leads to an effective dose of 6.0 mSv in a PET study using 400 MBq
      cis-FPro.

PMID- 11323240
TI  - Kinetic parameters of 3-[(123)I]iodo-L-alpha-methyl tyrosine ([(123)I]IMT)
      transport in human GOS3 glioma cells.
AB  - The radiolabelled amino acid 3-[(123)I]iodo-L-alpha-methyl tyrosine ([(123)I]IMT)
      is a promising tool for the diagnosis and monitoring of brain tumors using single
      photon emission tomography (SPECT). However, little is known about the precise
      kinetics of [(123)I]IMT uptake in human glioma cells. The kinetic analysis of
      [(123)I]IMT transport in human GOS3 glioma cells yielded a high-affinity apparent
      Michaelis constant (K(m) = 20.1 +/- 1.5 microM). The maximum transport velocity
      (V(max)) amounted to 34.8 +/- 1.9 nmol/mg protein/10 min. Competitive inhibition
      experiments revealed that [(123)I]IMT transport is mediated principally by the
      sodium-independent system L.

PMID- 11323241
TI  - Biodistribution and renal excretion of isomers of the cationic tracer, (99m)Tc
      diaminocyclohexane (DACH): biodistribution of cationic renal tracers.
AB  - The buildup of organic anions in the plasma in the uremic state can competitively
      inhibit the tubular extraction of para-aminohippurate or (131)I ortho
      iodohippurate (OIH) and lead to spuriously low measurements of effective renal
      plasma flow (ERPF). This problem can be circumvented by the use of cationic
      tracers. The cationic renal tracer, (99m)Tc labeled diaminocyclohexane ((99m)Tc
      DACH), has a clearance of 80% of OIH in mice but its clearance in humans is
      relatively low, only 30% of OIH. The (99m)Tc DACH isomer(s) used in prior
      studies, however, was not clearly defined and may have consisted of a single
      isomer or a combination of isomers. Since the anionic isomers of some (99m)Tc
      renal tracers have been shown to have widely different clearances, the
      biodistribution and urine excretion of the (99m)Tc cis-, trans-S,S, trans-R,R and
      +/-trans-DACH isomers were compared in Sprague-Dawley rats at 10 minutes and 60
      minutes postinjection to determine if one of the (99m)Tc DACH isomers may be a
      significantly better renal tracer than the others. The red cell binding of
      (99m)Tc +/- trans-DACH was also determined. All of the isomers showed a high
      degree of specificity for the kidney with minimal secretion into the
      gastrointestinal tract. Urine excretion of the 4 tracers, however, was only 38
      48% that of OIH at 10 minutes and 66-84% that of OIH at 60 minutes. Red cell
      binding was 6.9%. Cationic renal tracers have the potential to provide a more
      accurate measurement of ERPF than anionic tracers. Based on the animal data,
      however, it is unlikely that any of the (99m)Tc DACH isomers will have a
      substantially higher clearance in humans than the form of (99m)Tc DACH originally
      tested. Development of alternative cationic renal tracers is warranted.

PMID- 11323242
TI  - Effects of Tween-80 on the biodistribution of several lipophilic technetium-99m
      complexes.
AB  - The effects of Tween-80 on the biodistributions in mice of (99m)Tc-TBI, (99m)Tc
      MIBI, (99m)TcN-TBI and (99m)TcN-MIBI were reported. The studies resulted that
      liver and blood uptakes of Tween-80 added (TA) complexes significantly lower than
      that of corresponding non-Tween-80 added (NTA) complexes. And the clearance rate
      from blood of TA complexes faster than that of NTA complexes. The optimal
      concentration of Tween-80 was about 1%. It can decrease the lipophilicity of
      (99m)Tc-complexes and improve the biological properties of the lipophilic (99m)Tc
      complexes for myocardial imaging. It's worthy for further studies.

PMID- 11323243
TI  - Potential (166)Ho radiopharmaceuticals for intravascular radiation therapy (IVRT)
      I: [(166)Ho] holmium labeled ethylene dicysteine.
AB  - The use of beta(-) emitting radionuclides in the control of restenosis in post
      angioplasty patients is currently under intense investigation at many leading
      cardiovascular research centers. (32)P coated metallic stents, (192)Ir wire
      source and balloons filled with an appropriate radionuclide solution such as of
      (188)Re, attached to catheter are being studied. (166)Ho has comparable
      radionuclidic properties to that of (188)Re, can be more easily produced and
      hence is an attractive alternative to (188)Re. Ethylene dicysteine complex of
      (166)Ho was prepared and its pharmacological behavior studied. Optimum conditions
      for the preparation of complex with respect to the reaction time, ligand
      concentration, pH of the reaction mixture as well as reaction temperature were
      standardized. The stability of the labeled complex at room temperature as well as
      at 4 degrees C was determined. Biodistribution pattern of the injected complex in
      Wistar rats was estimated at 10 min, 30 min and 3 h post injection. This study
      indicated that >90% of the injected (166)Ho-EC complex was excreted in urine
      within 3 h post injection, with insignificant retention in any major organ. These
      studies reveal that (166)Ho-EC could be a viable substitute for (188)Re compounds
      in radioactive liquid-filled balloon IVRT.

PMID- 11323244
TI  - Uptake of (188)Re-beta-naphthyl-peptide in cervical carcinoma tumours in athymic
      mice.
AB  - Radiolabelled somatostatin analogues have been used in diagnostic and therapeutic
      nuclear medicine to treat cancerous tumours. Lanreotide, a cyclic octapeptide,
      beta-naphthyl-peptide, with antiproliferative action on human small cell lung
      carcinoma was (188)Re labelled and characterised, and its biodistribution was
      studied in mice. Molecular modelling indicates that the lipophilic
      radiopharmaceutical might be an oxo-rhenium (V) penta-coordinated complex. The
      implanted human cervical tumour of epidermoid origin was positive for
      cytokeratins and Vimentin. Uptake of (188)Re-labelled peptide in the implanted
      tumour in athymic mice was 6.2+/-2.9% and was rapidly cleared via the
      hepatobiliary system. (188)Re-beta-naphthyl-peptide might be a potential
      therapeutic agent.

PMID- 11323245
TI  - Radiotherapeutic efficacy of (153)Sm-CMDTPA-Tyr(3)-octreotate in tumor-bearing
      rats.
AB  - A number of radiolabeled somatostatin analogs have been evaluated in animal tumor
      models for radiotherapeutic efficacy. The majority of the agents tested have used
      either high-energy beta-emitters, such as Y-90 or Re-188, or the Auger electron
      emitting radionuclide, In-111. Because a medium-energy beta-emitter might have
      equivalent efficacy compared to high-energy emitters, and lower toxicity to non
      target tissues, we have evaluated the therapeutic potential of the beta-emitting
      nuclide, Sm-153, chelated to the somatostatin analog, CMDTPA-Tyr(3)-octreotate.
      Using an in vitro binding assay, this octreotate derivative was shown to have
      high affinity for the somatostatin subtype-2 receptor (IC(50) = 2.7 nM).
      Biodistribution studies in CA20948 tumor-bearing Lewis rats demonstrate that the
      Sm-153 labeled compound has high uptake and retention in tumor tissue (1.7%
      injected dose/g tissue, 4 hrs post injection) and has rapid overall clearance
      properties from non-target tissue. Radiotherapy studies were carried out using
      (153)Sm-CMDTPA-Tyr(3)-octreotate and CA20948 tumor bearing Lewis rats at 7 days
      post implant. Dose regimens consisting of single and multiple i.v. injections of
      5.0 mCi/rat (185 MBq) were employed over a time span of 7 days. Suppression of
      tumor growth rate was observed in all treated animals compared to untreated
      controls. Greater inhibition of tumor growth was observed in animals that
      received multiple doses. These studies indicate that medium-energy beta-emitting
      isotopes have considerable potential for the treatment of somatostatin receptor
      positive tumors.

PMID- 11323246
TI  - High performance liquid chromatographic determination of 123-I labeled tamoxifen
      metabolites in human plasma.
AB  - A high-performance liquid chromatographic procedure for the quantitation of
      [(123)I]Iodomethyl-N,N-diethyltamoxifen (ITX), a radioligand for human breast
      cancer imaging, in human plasma is described. Separation was effected on a RP-C18
      column, using a mixture of acetonitrile-water-triethylamine (70/30/0.5, v/v). ITX
      was rapidly cleared from human plasma and metabolites appeared as early as 7.5
      min p.i. Quantitative assessment of metabolites in plasma over time allowed
      recalculation of the ITX plasma time-activity curve. Implications of ITX
      metabolite formation for breast tumour imaging are discussed.

PMID- 11323248
TI  - Becoming aware of motor skill.
AB  - Conscious processes have a complex relationship to skilled motor performance.
      Past work has shown that some types of motor skill can be learned without any
      contribution from conscious processes. New work indicates that if those
      unconscious processes are disabled, conscious processes might step in to make up
      for the deficit.

PMID- 11323247
TI  - A simple and inexpensive preparation of [(51)Cr]-MAA particles.
AB  - The feasibility of preparing [(51)Cr]-MAA was investigated using an MAA cold kit
      and commercially available sodium [(51)Cr]chromate solutions. Of different
      conditions tested, the best required an addition of a low level of sodium
      dithionite to achieve a radiolabeling efficiency of 44%. The product was purified
      by centrifugation to give [(51)Cr]-MAA with 99 +/- 1% radiochemical purity (RCP)
      comprised of >94% radioactive particles >10 microm, and resulted in a rat
      biodistribution with >80% in the lungs. [(51)Cr]-MAA is inexpensive, easily and
      conveniently prepared by this procedure.

PMID- 11323249
TI  - Object-oriented models of cognitive processing.
AB  - Information-processing models of vision and cognition are inspired by procedural
      programming languages. Models that emphasize object-based representations are
      closely related to object-oriented programming languages. The concepts underlying
      object-oriented languages provide a theoretical framework for cognitive
      processing that differs markedly from that offered by procedural languages. This
      framework is well-suited to a system designed to deal flexibly with discrete
      objects and unpredictable events in the world.

PMID- 11323250
TI  - Asymmetries in preparation for action.
AB  - The origins and nature of hemispheric specialization of action control are
      unclear. A review of some recent evidence suggests that the right hemisphere
      interprets spatial relationships whereas the left deals with temporal control of
      movement. Contrary to the popular view, specialization of the right hemisphere
      for spatial representations might have preceded left hemisphere specialization
      for language and movement.

PMID- 11323251
TI  - Categorization in single neurons.

PMID- 11323252
TI  - Reasoning and world knowledge.

PMID- 11323253
TI  - Circuitry-based models of cognition.

PMID- 11323254
TI  - False beliefs and the frontal lobe.

PMID- 11323255
TI  - Premotor cortex called to attention.

PMID- 11323257
TI  - Universal dyslexia?

PMID- 11323256
TI  - Where the brain gets jokes.

PMID- 11323258
TI  - It's all in the timing.

PMID- 11323259
TI  - 'Seeing' sound.

PMID- 11323260
TI  - Bird-watching at a dog show?

PMID- 11323262
TI  - A taste for space.

PMID- 11323261
TI  - Memories stuck in a rut.

PMID- 11323263
TI  - Implicit memory: intention and awareness revisited.
AB  - One of the major developments in memory research in the past decade or so has
      been a growing interest in implicit memory - task performance that is not
      accompanied by conscious or intentional recollection. In this article, we examine
      evidence for perceptual and conceptual implicit memory, using the accepted
      definitions, and suggest that there is in fact a lack of strong evidence for
      implicit memory in normal subjects. If more convincing evidence cannot be
      obtained, one solution might be to modify the current terminology. We suggest
      that the term implicit memory might have outgrown its usefulness as an overall
      descriptor.

PMID- 11323264
TI  - Surface perception and the generic view principle.
AB  - The hypothesis that perceptual experience can be understood in terms of rule
      based processing has strongly influenced recent theories of visual surface
      perception. However, many of the rules that these theories propose apply only in
      relatively restricted situations. I suggest that more general and robust
      principles for reducing perceptual ambiguity are available, such as the generic
      view principle (GVP) described here. According to the GVP, vision assumes that
      qualitative (e.g. topological) image structure is stable with respect to small
      changes of viewpoint. Some consequences of the GVP for visual surfaces, including
      illusory surfaces, are described. I also demonstrate the decisive role of real
      and illusory background surfaces in specifying the 3-D shape and layout of visual
      objects and scenes.

PMID- 11323265
TI  - The neurobiology of human category learning.
AB  - Categorization is among the most important skills that any organism can possess.
      Recent advances in cognitive neuroscience have led to new insights about the
      neural basis of category learning. Perhaps most important is the finding that
      many different, widely separated neural structures appear to participate in
      category learning, but to varying degrees that depend on category structure. In
      particular, different brain regions are implicated according to whether the
      category-learning task involves explicit rules, prototype distortion or
      information integration.

PMID- 11323266
TI  - The role of color in high-level vision.
AB  - Traditional theories of object recognition have emphasized the role of shape
      information in high-level vision. However, the accumulating behavioral,
      neuroimaging and neuropsychological evidence indicates that the surface color of
      an object affects its recognition. In this article, we discuss the research that
      examines the conditions under which color influences the operations of high-level
      vision and the neural substrates that might mediate these operations. The
      relationship between object color and object recognition is summarized in the
      'Shape+Surface' model of high-level vision.

PMID- 11323267
TI  - Animal cognition and the rat olfactory system.
AB  - Is smell a 'primitive' sense used primarily to guide biologically basic behaviors
      or might it be the sensory modality that allows some species to express complex
      learning and other forms of cognitive behavior? Historically, the olfactory
      system has been considered primitive and it is not surprising that, until
      recently, cognitive neuroscientists have ignored odor-guided behavior. However,
      we now know that the olfactory system has projections to the prefrontal cortex,
      entorhinal cortex and hippocampus, and that these connections support the
      acquisition of simple and higher-order instrumental tasks, as well as a robust
      memory for odors. It appears that animals with a well-developed sense of smell
      have the neural machinery to think with their noses.

PMID- 11323268
TI  - The human genome: an immuno-centric view of evolutionary strategies.
AB  - A hallmark of modern biology is the realization of the fundamental unity of
      biological processes in all life forms. Consequently, the complete genome
      sequencing of various bacteria, yeast (Saccharomyces cerevisiae), fly (Drosophila
      melanogaster) and worm (Caenorhabditis elegans) over the past five years has
      already had an impact on all of biology. "Model organisms" have contributed a
      great deal to immunology; for example, the Toll receptors of the fly provided the
      impetus for the investigation of Toll-like receptors, which proved to be
      fundamental elements in the mammalian innate immune system. The recent release of
      a draft sequence of the human genome provides the first panoramic view of the
      30000-35000 human genes in the human genetic blueprint and provides a plethora of
      new details, the significance of which will take some time to appreciate. The
      over-riding concepts that emerge from these studies relate primarily to general
      evolutionary processes that are equally as relevant to immunology as they are to
      other disciplines of biology.

PMID- 11323269
TI  - Human mast cells and basophils in HIV-1 infection.
AB  - Mast cells and basophils (FcvarepsilonRI(+) cells) are classically involved in
      allergic disorders. HIV-1 glycoprotein gp120 acts as a viral superantigen by
      interacting with the heavy chain, variable 3 (V(H)3) region of IgE to induce
      cytokine release from FcvarepsilonRI(+) cells. The chemokine receptors CCR3 and
      CXCR4, co-receptors for HIV-1, are expressed by FcvarepsilonRI(+) cells. Via its
      interaction with CCR3, HIV-1 transactivation (Tat) protein is a potent
      chemoattractant for FcvarepsilonRI(+) cells. Incubation of basophils with Tat
      protein upregulates the surface expression of the CCR3 receptor. There is some
      evidence that human FcvarepsilonRI(+) cells could be infected in vitro by M
      tropic HIV-1 strains.

PMID- 11323270
TI  - NO-releasing NSAIDs are caspase inhibitors.
AB  - Nitrosation of thiol-containing proteins is a mechanism for cell regulation.
      Nitric-oxide-releasing nonsteroidal anti-inflammatory drugs (NO-NSAIDs) are
      chemical entities obtained by adding a nitroxybutyl moiety to a conventional
      NSAID. NO-NSAIDs inhibit inflammation via cyclo-oxygenase (COX)-dependent and 
      independent effects. Similarly to endogenous NO, NO-NSAIDs are potent inhibitors
      of T helper1 (Th1) type cytokines. This effect is largely owing to post
      translational nitrosation and therefore inactivation of cysteine proteases, such
      as the interleukin (IL)-1beta converting enzyme (ICE/caspase-1) involved in pro
      cytokine processing.

PMID- 11323271
TI  - The impact of glycobiology on medicine.
AB  - Proteins essential to normal cell physiology are usually glycosylated and
      variation in their glycosylation patterns often leads to changes in their
      function. Changes in glycosylation pattern can also be associated with disease.
      It is now becoming increasingly clear how important it is to understand these
      changes, to gain insight into their involvement in disease mechanisms and the
      potential for novel therapeutic interventions.

PMID- 11323272
TI  - A holistic view of memory generation: where do T cells reside?

PMID- 11323273
TI  - Getting TCR transgenics to work on time.

PMID- 11323274
TI  - The flip side of Fas.

PMID- 11323275
TI  - First human myeloma cell-line.

PMID- 11323276
TI  - An AIDS vaccine in sight?

PMID- 11323277
TI  - Self-peptide anaphylaxis.

PMID- 11323278
TI  - Good news for allergic cat-owners.

PMID- 11323279
TI  - Aspirin inhibits IL-4 production.

PMID- 11323280
TI  - IL-12 and Th1 immune responses in human Peyer's patches.
AB  - Oral tolerance is a well-characterized phenomenon in animals and is highly
      effective when induced as a treatment for experimental autoimmune disease.
      However, its use as a therapeutic modality for the treatment of autoimmune
      disease in humans has been disappointing. Much of the rationale for its use in
      humans is based on the finding that feeding antigen to rodents elicits regulatory
      T cells in Peyer's patches (PPs) that secrete immunosuppressive cytokines such as
      transforming growth factor (TGF)-beta. By contrast, human antigen-specific PP T
      cell responses, and mucosal T-cell responses in general, are strongly biased
      towards T helper 1 (Th1) cells, which are pro-inflammatory rather than
      immunosuppressive. This is caused by the high local levels of interleukin (IL)-12
      in PPs.

PMID- 11323281
TI  - A role for eosinophils in transplant rejection.
AB  - Eosinophils release inflammatory mediators and cationic proteins that are
      instrumental in the pathogenesis of allergic diseases such as bronchial asthma.
      Here, we review experimental observations indicating that eosinophils are also
      involved in the rejection of allografts. We propose that their role as effectors
      of transplant damage becomes crucial when classical pathways of rejection are
      inhibited and T helper 2 (Th2) cells dominate the alloimmune response.

PMID- 11323282
TI  - Thymic function and peripheral T-cell homeostasis in rheumatoid arthritis.
AB  - T-cell diversity is generated through the production of new thymic emigrants.
      Thymic function declines with age, and the T-cell pool is maintained through
      homeostatic proliferation of naive peripheral T cells. This article discusses the
      impact of thymic output and peripheral T-cell homeostasis on the development of
      rheumatoid arthritis (RA). It is proposed that thymic output is prematurely
      compromised in RA patients. A compensatory expansion of peripheral T cells
      results in a contracted and distorted repertoire, possibly favoring T cells with
      autoreactive potential. Increased risk of autoimmunity, as a consequence of
      abnormal T-cell population dynamics, could be a common mechanism in chronic
      inflammatory diseases.

PMID- 11323283
TI  - Macrophages and T-cell apoptosis in HIV infection: a leading role for accessory
      cells?
AB  - Recent studies indicate that macrophages modulate T-cell apoptosis in HIV
      infection. Macrophages have been shown to trigger apoptosis of uninfected
      bystander T cells and to protect HIV-infected T cells from apoptosis. This
      article raises the possibility that macrophages, via modulation of T-cell
      apoptosis, play a crucial role in both immune suppression and the formation of
      viral reservoirs during HIV infection.

PMID- 11323284
TI  - Drosophila immunity: two paths to NF-kappaB.
AB  - Recent studies of Drosophila immune responses have defined the immune deficiency
      (IMD) signaling pathway that mediates defense against Gram-negative bacterial
      infection. Like the Toll pathway, the IMD pathway regulates antimicrobial peptide
      gene expression via a Rel/nuclear factor (NF)-kappaB-like transcription factor.
      However, the two pathways do not appear to share any intermediate components.
      Maintaining distinct immune response pathways might be one mechanism by which
      flies mount adapted immune responses.

PMID- 11323285
TI  - PD-1: an inhibitory immunoreceptor involved in peripheral tolerance.
AB  - PD-1 deficiency causes a variety of autoimmune diseases. Inhibitory signaling
      through the PD-1 receptor might therefore be involved in the regulation of
      peripheral tolerance. The constitutive expression of PD-1 ligands (PD-L1 and PD
      L2) on parenchymal cells of heart, lung and kidney suggests that the PD-1-PD-L
      system could provide unique negative signaling to help prevent autoimmune
      diseases.

PMID- 11323286
TI  - The role of MHC class II-restricted tumor antigens and CD4+ T cells in antitumor
      immunity.
AB  - The identification of tumor antigens has generated a resurgence of interest in
      immunotherapy for cancer. However, both clinical and animal studies suggest that
      therapeutic strategies that have mainly focused on the use of CD8+ T cells (and
      MHC class I-restricted tumor antigens) are not effective in eliminating cancer
      cells. Recent interest has been directed towards the use of CD4+ T cells in
      generating antitumor immunity. To this end, the identification of MHC class II
      restricted tumor antigens that can stimulate CD4+ T cells might provide
      opportunities for developing effective cancer vaccines.

PMID- 11323287
TI  - Chemokines and lymphopoiesis in human thymus.
AB  - Distinct and redundant chemokines are responsible for organizing the
      extraordinarily diverse thymocyte populations into discrete microenvironments,
      from the arrival of immature precursors in the thymus to the migration of
      different mature cell types to the periphery. We propose that, by selectively
      mobilizing cells, chemokines can sort positively selected cells from negatively
      selected cells, and that chemokines make distinctions among CD8+ subpopulations
      that previously have not been recognized.

PMID- 11323290
TI  - Immunity to malaria increases during puberty.

PMID- 11323288
TI  - Plasmodium invasion of mosquito cells: hawk or dove?

PMID- 11323291
TI  - Ribosomal internal transcribed spacers separate triatomines.

PMID- 11323292
TI  - The human genome: what's in it for parasitologists?

PMID- 11323293
TI  - Social marketing of insecticide-treated bednets.

PMID- 11323304
TI  - Pre-erythrocytic immunity to Plasmodium falciparum: the case for an LSA-1
      vaccine.
AB  - A vaccine is urgently needed to stem the global resurgence of Plasmodium
      falciparum malaria. Vaccines targeting the erythrocytic stage are often viewed as
      an anti-disease strategy. By contrast, infection might be completely averted by a
      vaccine against the liver stage, a pre-erythrocytic stage during which the
      parasite multiplies 10000-fold within hepatocytes. Sterilizing immunity can be
      conferred by inoculating humans with irradiated pre-erythrocytic parasites, and a
      recombinant pre-erythrocytic vaccine partially protects humans from infection.
      Liver-stage antigen-1, one of a few proteins known to be expressed by liver-stage
      parasites, holds particular promise as a vaccine. Studies of naturally exposed
      populations have consistently related immune responses against this antigen to
      protection.

PMID- 11323305
TI  - Is lipophosphoglycan a virulence factor? A surprising diversity between
      Leishmania species.
AB  - Lipophosphoglycan is a prominent member of the phosphoglycan-containing surface
      glycoconjugates of Leishmania. Genetic tests enable confirmation of its role in
      parasite virulence and permit discrimination between the roles of
      lipophosphoglycan and related glycoconjugates. When two different
      lipophosphoglycan biosynthetic genes from Leishmania major were knocked out,
      there was a clear loss of virulence in several steps of the infectious cycle but,
      with Leishmania mexicana, no effect on virulence was found. This points to an
      unexpected diversity in the reliance of Leishmania species on virulence factors,
      a finding underscored by recent studies showing great diversity in the host
      response to Leishmania species.

PMID- 11323306
TI  - Schistosome male-female interaction: induction of germ-cell differentiation.
AB  - Male and female schistosomes are permanently paired while they live in the
      bloodstream of their vertebrate hosts. Female schistosomes produce eggs only when
      they are in intimate association with a male. Here, I combine classical
      cytological knowledge about the cellular processes in the female that are
      affected by the male with recent molecular results that are beginning to allow
      speculation about the signalling events involved.

PMID- 11323307
TI  - Mass spectrometric strategies: providing structural clues for helminth
      glycoproteins.
AB  - Here we review current knowledge of helminth glycans and introduce
      parasitologists to the power of the mass spectrometric techniques that have been
      largely responsible for defining their carbohydrate moieties. A brief overview of
      glycosylation in other eukaryotes is presented, with a focus on mammalian
      glycosylation, to facilitate understanding of how parasite structures might be
      recognized as 'self' or 'foreign' by the immune system of the host.

PMID- 11323308
TI  - Of mice and malaria mutants: unravelling the genetics of drug resistance using
      rodent malaria models.
AB  - It is well recognized that drug resistance is the most significant obstacle to
      gaining effective malaria control. Despite the enormous advances in the knowledge
      of the biochemistry and molecular biology of malaria parasites, only a few genes
      determining resistance to the commonly used drugs have been identified. The idea
      that rodent malaria parasites should be exploited more widely for such work, in
      view of the practical problems of studying this subject experimentally in human
      malaria, is presented.

PMID- 11323309
TI  - Targeting polyamines of parasitic protozoa in chemotherapy.
AB  - All parasitic protozoa contain polyamines and in recent years they, and their
      associated enzymes, have attracted attention as drug targets because they might
      reveal novel antiparasite therapies. How justified is this approach to drug
      discovery? In this review, Sylke Muller, Graham Coombs and Rolf Walter summarize
      the current status of research into drugs that exploit polyamine metabolism of
      trypanosomatid and malaria parasites, and propose priorities for research into
      such drugs. This review was inspired by an Expert Meeting entitled 'Polyamine
      Metabolism of Parasitic Protozoa as a Drug Target'.

PMID- 11323311
TI  - Leukemia, brain tumors, and exposure to extremely low frequency electromagnetic
      fields in Swiss railway employees.
AB  - Railway engineers provide excellent opportunities for studying the relation
      between exposure to extremely low frequency magnetic fields and leukemia or brain
      tumors. In a cohort study of Swiss railway personnel with 2.7 x 10(5) person
      years of follow-up (1972--1993), the authors compared occupations with high
      average exposures (line engineers: 25.9 microT) to those with medium and low
      exposures (station masters: 1 microT). The mortality rate ratio for leukemia was
      2.4 (95% confidence interval (CI): 1.0, 6.1) among line engineers (reference
      category: station masters). The mortality rate ratio for brain tumors was 1.0
      (95% CI: 0.2, 4.6) among line engineers and 5.1 (95% CI: 1.2, 21.2) among
      shunting yard engineers (compared with station masters). Two exposure
      characteristics were evaluated: cumulative exposure in microT-years and years
      spent under exposure to magnetic fields of > or =10 microT. There was a
      significant increase in leukemia mortality of 0.9% (95% CI: 0.2, 1.7) per microT
      year of cumulative exposure to extremely low frequency magnetic fields. The
      increase by years spent under exposure of > or =10 microT was even stronger: 62%
      per year (95% CI: 15, 129). Brain cancer risk did not show a dose-response
      relation. This study contributes to the evidence for a link between heavy
      exposure to extremely low frequency magnetic fields and leukemia. Its strengths
      include reliable measurements and reliable historical reconstruction of
      exposures.

PMID- 11323312
TI  - Invited commentary: electromagnetic fields and cancer in railway workers.
AB  - The ideal study of occupational exposure to electromagnetic fields and cancer
      risk would have a clear exposure source, historically stable exposures, and
      comparable groups of exposed and unexposed workers. Cohorts of railway workers
      have marked exposure contrasts and limited job changes and provide marginally
      adequate study sizes, but there have been important changes in their exposures
      over time, and the field frequency involved is unusual. The results of Minder and
      Pfluger's study (Am J Epidemiol 2001;153:825--35) add modest support for an
      association between electromagnetic field exposure and leukemia. However, given
      the large size and high quality of a number of previous studies of occupational
      electromagnetic field exposure and cancer, additional studies similar to past
      ones are unlikely to yield important new insights.

PMID- 11323314
TI  - Risk of pancreatic cancer in workers exposed to chlorinated hydrocarbon solvents
      and related compounds: a meta-analysis.
AB  - This is a meta-analysis of occupational exposures to chlorinated hydrocarbon
      (CHC) solvents and pancreatic cancer, based primarily on studies that addressed
      exposure directly (agent studies) and secondarily on studies that reported data
      without verification of individual CHC exposures (job title studies), all of
      which were listed in databases for the period January 1969 to May 1998.
      Standardized extraction of data and double-checking of consistency of data
      extraction by five extractors were done. Simple random models estimated meta
      relative risks. Suggestive weak excesses were found for trichloroethylene (meta
      relative risk (MRR) = 1.24, 95% confidence interval (CI): 0.79, 1.97),
      polychlorinated biphenyls (MRR = 1.37, 95% CI: 0.56, 3.31), methylene chloride
      (MRR = 1.42, 95% CI: 0.80, 2.53), and vinyl chloride (MRR = 1.17, 95% CI: 0.71,
      1.91) but not for carbon tetrachloride. One study addressed tetrachloroethylene
      (MRR = 3.08, 95% CI: 0.63, 8.99); another investigated chlorohydrin production
      (MRR = 4.92, 95% CI: 1.58, 11.4). Exposure-response meta-analyses for
      trichloroethylene and methylene chloride failed to reveal trends. Job title
      studies on metal degreasing and dry cleaning revealed significant MRRs (2.0 and
      1.4, respectively). Publication bias was unlikely. Confounding may have remained
      insufficiently controlled. Unless the results are seriously biased by exposure or
      endpoint misclassification or by confounding, strong causal associations between
      CHC compounds and pancreatic cancer can be judged unlikely. Interactions between
      environmental and occupational agents, lifestyle factors, and genetic
      susceptibility remain a possibility, but the data for this meta-analysis did not
      address interactions.

PMID- 11323315
TI  - Gene-environment interactions in renal cell carcinoma.
AB  - The majority of renal cell carcinomas (RCCs) are sporadic, and increasing
      incidence rates suggest that such environmental risk factors as smoking play a
      role in the etiology of the disease. Cases with RCC were selected from the
      population-based cancer registry of Orange County, California, between 1994 and
      1997; controls were recruited by telephone using random digit dialing. A total of
      115 case and 259 control subjects were genotyped for N-acetyltransferase 2
      (NAT2), which codes for a polymorphic enzyme involved in tobacco-carcinogen
      metabolism. Subjects with slow acetylator genotypes were found to be at twofold
      increased risk (odds ratio (OR) = 1.8; 95 percent confidence interval (CI): 1.1,
      2.9) of RCC. Although cancer risk doubled among smokers (OR = 2.2; 95 percent CI:
      1.3, 3.7), stratified analysis revealed gene-environment interaction among slow
      acetylators that smoked (OR = 3.2; 95 percent CI: 1.7, 6.1) compared with rapid
      acetylators that smoked (OR = 1.4; 95 percent CI: 0.7, 2.9). A dose response was
      found for pack-years among slow acetylators (p < 0.01) but not among rapid
      acetylators (p = 0.06). Although smoking is a well-established risk factor of
      RCC, our data suggest that the risk is pronounced among slow rather than rapid
      acetylators.

PMID- 11323316
TI  - Reproduction-related risk factors for mucinous and nonmucinous epithelial ovarian
      cancer.
AB  - The proposition that mucinous ovarian cancer has an etiology distinct from that
      of other histologic types has been evaluated using data from a population-based
      case-control study of epithelial ovarian cancer conducted in 1990--1993 among
      Australian women aged 18--79 years. The protective effects of parity and oral
      contraceptive use were greater in nonmucinous than in mucinous ovarian tumors.
      However, these differences appeared to be driven largely by the effect of
      ovulatory life, which was positively associated with nonmucinous tumors only. An
      association with family history of breast and/or ovarian cancer also appeared to
      be restricted to nonmucinous cancers. These results lend support to the
      hypothesis that mucinous and nonmucinous ovarian tumors develop via different
      causal mechanisms.

PMID- 11323317
TI  - Factors associated with age at natural menopause in a multiethnic sample of
      midlife women.
AB  - An unprecedented number of women will experience menopause in the next decade.
      Although the timing of menopause affects long-term disease risk, little is known
      about factors that affect this timing. In the present 1995--1997 cross-sectional
      study, the Study of Women's Health Across the Nation, the relation of demographic
      and lifestyle factors to age at natural menopause was examined in seven US
      centers and five racial/ethnic groups. All characteristics were self-reported by
      women aged 40--55 years (n = 14,620). Cox proportional hazards models were used
      to estimate the probability of menopause by age. Overall, median age at natural
      menopause was 51.4 years, after adjustment for smoking, education, marital
      status, history of heart disease, parity, race/ethnicity, employment, and prior
      use of oral contraceptives. Current smoking, lower educational attainment, being
      separated/widowed/divorced, nonemployment, and history of heart disease were all
      independently associated with earlier natural menopause, while parity, prior use
      of oral contraceptives, and Japanese race/ethnicity were associated with later
      age at natural menopause. This sample is one of the largest and most diverse ever
      studied, and comprehensive statistical methods were used to assess factors
      associated with age at natural menopause. Thus, this study provides important
      insights into this determinant of long-term disease risk in women.

PMID- 11323318
TI  - Prospective study of cataract extraction and risk of coronary heart disease in
      women.
AB  - Oxidative damage to proteins in the human lens is believed to be important in the
      etiology of age-related cataract. Because free radical-mediated oxidative damage
      to lipoproteins may accelerate atherosclerosis, the authors hypothesized that the
      development of cataract might be a marker for such damage and therefore might be
      associated with future risk of coronary heart disease (CHD). The authors followed
      60,657 women aged 45--63 years and without known coronary disease, stroke, or
      cancer in 1984. During 10 years of follow-up (674,283 person-years), the authors
      documented 887 incident cases of CHD and 2,322 deaths. After adjustment for age,
      smoking, and other coronary risk factors, cataract extraction was significantly
      associated with higher risk of CHD (relative risk (RR) = 1.88, 95% confidence
      interval (CI): 1.41, 2.50) for total CHD, 2.44 (95% CI: 1.54, 3.89) for fatal
      CHD, and 1.63 (95% CI: 1.14, 2.34) for nonfatal myocardial infarction). The
      positive association between cataract extraction and total CHD was stronger among
      women with a history of diabetes (RR = 2.80, 95% CI: 1.77, 4.42) than among those
      without reported diabetes (RR = 1.51, 95 percent CI: 1.04, 2.18). In multivariate
      analyses, cataract extraction was associated with significantly increased overall
      mortality (RR = 1.37, 95 percent CI: 1.13, 1.66), which was entirely explained by
      the increased mortality from cardiovascular disease (RR = 1.84, 95% CI: 1.29,
      2.64). These findings are compatible with current hypotheses relating oxidative
      damage and tissue aging to the development of cataract and CHD.

PMID- 11323319
TI  - Application of the induced exposure method to compare risks of traffic crashes
      among different types of drivers under different environmental conditions.
AB  - The authors used the induced exposure method to compare risks of traffic crashes
      among different types of Spanish drivers under different environmental
      conditions. The authors analyzed traffic crashes recorded by the Spanish
      Direccion General de Trafico for the years 1991 and 1992 to compare proportions
      of drivers in different age/sex categories who were involved in single-vehicle
      and multivehicle crashes under different psychological and physical conditions.
      Crash risk was 1.42- to 2.35-fold greater in men than in women, depending on
      driver category and environmental factors. Risk was also significantly higher in
      the 18- to 24-year-old age group (1.75- to 2.87-fold greater than in drivers aged
      25-49 years) and under abnormal psychological-physical conditions (1.69- to 4.10
      fold greater among drivers under the influence of alcohol). Twilight and night
      driving, driving in urban areas, and driving on weekends and legal holidays were
      also associated, though nonsignificantly, with a slightly higher traffic crash
      risk. These findings are consistent with earlier reports, and they support the
      usefulness of the induced exposure method as an easy and economical tool with
      which to analyze data contained in traffic crash records.

PMID- 11323320
TI  - Vitamin supplement use and diabetes mellitus incidence among adults in the United
      States.
AB  - In some studies, use of vitamin supplements has been inversely associated with
      the risk of several chronic diseases, but little is known about whether vitamin
      use affects the risk of diabetes mellitus. Using data from the National Health
      and Nutrition Examination Survey I Epidemiologic Follow-up Study, the author
      examined whether vitamin use was related to diabetes incidence in a cohort of
      United States adults aged 25--74 years. In the analytic sample of 9,573
      participants, 1,010 participants developed diabetes mellitus during about 20
      years of follow-up. A smaller percentage of participants with incident diabetes
      (21.4%) reported using vitamins during the previous month at baseline compared
      with participants who remained free of this disease (33.5%) (p < 0.001). After
      multiple adjustment, the hazard ratios for participants using vitamin supplements
      were 0.76 (95% confidence interval (CI): 0.63, 0.93) for all participants, 0.70
      (95% CI: 0.54, 0.92) for men, and 0.84 (95% CI: 0.64, 1.11) for women. Sex did
      not modify the association between vitamin use and diabetes incidence. Whether
      specific vitamins or other factors closely correlated with vitamin use account
      for this observation is unclear.

PMID- 11323321
TI  - Effect of combination therapy on immunologic progression of human
      immunodeficiency virus at a population level.
AB  - There is accumulating evidence from clinical trials and cohort studies that
      highly active antiretroviral combination therapy is effective at halting
      immunologic and clinical progression of human immunodeficiency virus (HIV). Its
      impact at a population level is less well known because the regimes may be
      difficult to tolerate and compliance poorer. The authors make use of population
      data for almost all of the HIV-infected people in Scotland in 1997 who were under
      clinical care and monitor their response to therapy during the first year when
      these effective treatments became widely available. More than two thirds of the
      HIV-positive patients were on some form of antiretroviral therapy during the
      year. The authors show that all treated groups, even those who were on changing
      regimes, showed net improvement in immunologic status during the year. For the
      group of patients on triple or quadruple therapy, there was an average increase
      of more than 100 CD4 cells/mm(3) over the year, with other treatment groups
      showing more modest, but significant, increases.

PMID- 11323322
TI  - Postsanatorium pattern of antituberculous drug resistance in the Canadian-born
      population of western Canada: effect of outpatient care and immigration.
AB  - Concurrent with the shift in tuberculosis case management from sanatorium to
      outpatient setting was a shift in the continent of origin (Europe to Asia) of
      most new immigrants to CANADA: To assess the impact of these two events on
      antituberculous drug resistance in the Canadian-born population, the authors
      reviewed the results of six drug resistance surveys conducted in the two
      westernmost provinces of Canada between 1963 and 1994. Survey data were
      complemented by new molecular diagnostic and contact tracing data collected over
      5 years (1994--1998) in one of the three large urban centers of the region. Over
      the time spanned by the surveys, there was no increase in the proportion of all
      Canadian-born tuberculosis cases who relapsed or the proportion of all Canadian
      born relapsed cases who were drug resistant (approximately 12--13%). In addition,
      the prevalence of primary drug resistance among Canadian-born cases did not
      increase; rates consistently averaged between 2% and 5% despite a doubling of
      primary resistance rates among foreign-born cases. Molecular diagnostic and
      contact tracing data strongly supported the survey findings. The authors
      concluded that outpatient care and immigration have thus far had no measurable
      impact on the pattern of antituberculous drug resistance in the Canadian-born
      population of western CANADA:

PMID- 11323323
TI  - Incidence of herpes simplex virus type 2 infection in the United States.
AB  - Between the time that two large, national surveys were conducted, the Second
      National Health and Nutrition Examination Survey (1976-1980) and the Third
      National Health and Nutrition Examination Survey (1988-1994), prevalence of
      herpes simplex virus type 2 (HSV-2) infection in the United States increased by
      30%. From these survey data, the authors estimated the incidence of HSV-2
      infection in the civilian, noninstitutionalized population aged > or = 12 years
      by means of a mathematical model that allowed overall incidence to increase
      linearly with time but required the shape of the age-specific incidence curve to
      remain constant. From 1970 to 1985, annual incidence of HSV-2 infection in HSV-2
      seronegative persons increased by 82%, from 4.6 per 1,000 (95% confidence
      interval: 4.2, 5.0) to 8.4 per 1,000 (95% confidence interval: 7.7, 9.1).
      Incidence in 1985 was higher in women than in men (9.9 vs. 6.9 per 1,000), higher
      in Blacks than in Whites (20.4 vs. 6.3 per 1,000), and highest in the group aged
      20-29 years (14.6 and 22.5 per 1,000 in men and women, respectively). Thus, by
      1985, approximately 1,640,000+/-150,000 persons (730,000 men and 910,000 women)
      were being infected annually with HSV-2.

PMID- 11323324
TI  - Screening without a "gold standard": the Hui-Walter paradigm revisited.
AB  - The authors consider screening populations with two screening tests but where a
      definitive "gold standard" is not readily available. They discuss a recent
      article in which a Bayesian approach to this problem is developed based on data
      that are sampled from a single population. It was subsequently pointed out that
      such inferences will not necessarily be accurate in the sense that standard
      errors for parameters may not decrease as n increases. This problem will
      generally occur when the data are insufficient to estimate all of the parameters
      as is the case when screening a single population with two tests. If both tests
      are applied to units sampled from two populations, however, this particular
      difficulty disappears. In this article the authors further examine this issue and
      develop an approach based on sampling two populations that yields increasingly
      accurate inferences as the sample size increases.

PMID- 11323325
TI  - Fast-tracking after coronary artery bypass graft surgery.

PMID- 11323327
TI  - A randomized double-blinded multicenter comparison of remifentanil versus
      fentanyl when combined with isoflurane/propofol for early extubation in coronary
      artery bypass graft surgery.
AB  - We compared a fentanyl/isoflurane/propofol regimen with a
      remifentanil/isoflurane/propofol regimen for fast-track cardiac anesthesia in a
      prospective, randomized, double-blinded study on patients undergoing elective
      coronary artery bypass graft surgery. Anesthesia was induced with a 1-min
      infusion of 0.5 mg/kg propofol followed by 10-mg boluses of propofol every 30 s
      until loss of consciousness. After 0.2 mg/kg cisatracurium, a blinded continuous
      infusion of remifentanil at 1 microg. kg(-1). min(-1) or the equivalent volume
      rate of normal saline was then started. In addition, a blinded bolus syringe of 1
      microg/kg remifentanil or 10 microg/kg fentanyl, respectively, was given over 3
      min. Blinded remifentanil, 1 microg. kg(-1). min(-1) (or the equivalent volume
      rate of normal saline), together with 0.5% isoflurane, were used to maintain
      anesthesia. Significantly more patients (P < 0.01) in the fentanyl regimen
      experienced hypertension during skin incision and maximum sternal spread compared
      with patients in the remifentanil regimen. There were no differences between the
      groups in time until extubation, discharge from the surgical intensive care unit,
      ST segment and other electrocardiogram changes, catecholamine levels, or cardiac
      enzymes. The remifentanil-based anesthetic (consisting of a bolus followed by a
      continuous infusion) resulted in significantly less response to surgical
      stimulation and less need for anesthetic interventions compared with the fentanyl
      regimen (consisting of an initial bolus, and followed by subsequent boluses only
      to treat hemodynamic responses) with both drug regimens allowing early
      extubation. IMPLICATIONS: Both fentanyl and the newer opioid remifentanil, when
      each is combined with isoflurane and propofol, allowed for fast-track cardiac
      anesthesia. The remifentanil regimen used in this study resulted in significantly
      less hemodynamic response to surgical stimulation.

PMID- 11323328
TI  - The efficacy and resource utilization of remifentanil and fentanyl in fast-track
      coronary artery bypass graft surgery: a prospective randomized, double-blinded
      controlled, multi-center trial.
AB  - We compared (a) the perioperative complications; (b) times to eligibility for,
      and actual time of the following: extubation, less intense monitoring, intensive
      care unit (ICU), and hospital discharge; and (c) resource utilization of nursing
      ratio for patients receiving either a typical fentanyl/isoflurane/propofol
      regimen or a remifentanil/isoflurane/propofol regimen for fast-track cardiac
      anesthesia in 304 adults by using a prospective randomized, double-blinded,
      double-dummy trial. There were no differences in demographic data, or
      perioperative mortality and morbidity between the two study groups. The mini
      mental status examination at postoperative Days 1 to 3 were similar between the
      two groups. The eligible and actual times for extubation, less intense
      monitoring, ICU discharge, and hospital discharge were not significantly
      different. Further analyses revealed no differences in times for extubation and
      resource utilization after stratification by preoperative risk scores, age, and
      country. The nurse/patient ratio was similar between the
      remifentanil/isoflurane/propofol and fentanyl/isoflu-rane/propofol groups during
      the initial ICU phase and less intense monitoring phase. Increasing preoperative
      risk scores and older age (>70 yr) were associated with longer times until
      extubation (eligible), ICU discharge (eligible and actual), and hospital
      discharge (eligible and actual). Times until extubation (eligible and actual) and
      less intense monitoring (eligible) were significantly shorter in Canadian
      patients than United States' patients. However, there was no difference in
      hospital length of stay in Canadian and United States' patients. We conclude that
      both anesthesia techniques permit early and similar times until tracheal
      extubation, less intense monitoring, ICU and hospital discharge, and reduced
      resource utilization after coronary artery bypass graft surgery. IMPLICATIONS: An
      ultra-short opioid technique was compared with a standard fast-track small-dose
      opioid technique in coronary artery bypass graft patients in a prospective
      randomized, double-blinded controlled study. The postoperative recovery and
      resource utilization, including stratification of preoperative risk score, age,
      and country, were analyzed.

PMID- 11323329
TI  - The adequacy of basic intraoperative transesophageal echocardiography performed
      by experienced anesthesiologists.
AB  - Transesophageal echocardiography (TEE) may improve intraoperative decision-making
      and patient outcome if it is performed and interpreted correctly. After revising
      our TEE examination to fulfill the published guidelines for basic TEE
      practitioners, we prospectively evaluated the ability of our cardiac
      anesthesiologists (all very experienced with TEE) to record and interpret this
      revised examination. Educational aids and regular TEE performance feedback were
      provided to the anesthesiologists. Their interpretations were compared with the
      independently determined results of experts. Compared with their own historical
      controls (42% recording rate), all anesthesiologists showed significant
      improvement in their ability to record a basic intraoperative TEE examination
      resulting in 81% (P < 0.0001) of all required images being recorded: 88% before
      cardiopulmonary bypass, 77% immediately after bypass, and 64% after chest
      closure. Seventy-nine percent of the images recorded at baseline were correctly
      interpreted, 6% were incorrectly interpreted, and 15% were not evaluated. Our
      attempt to assess compliance with published guidelines for basic intraoperative
      TEE resulted in a marked improvement in our intraoperative TEE practice. Most,
      but not all, standard cross-sections are recorded or interpreted correctly, even
      by highly experienced and motivated practitioners. IMPLICATIONS: Experienced
      cardiac anesthesiologists can obtain and correctly interpret most basic
      intraoperative transesophageal echocardiograms.

PMID- 11323330
TI  - The detection of interatrial flow patency in awake and anesthetized patients: a
      comparative study using transnasal transesophageal echocardiography.
AB  - The Valsalva maneuver in the awake patient and the ventilation maneuver in the
      tracheally intubated anesthetized patient are two provocation methods to detect a
      patent foramen ovale (PFO) by means of contrast transesophageal echocardiography.
      In 60 patients undergoing posterior fossa surgery, a contrast agent was
      administered via a peripheral vein during a Valsalva maneuver immediately before
      anesthesia induction, followed by central venous administration during a
      ventilation maneuver in the same patients when anesthetized and endotracheally
      intubated. We evaluated both maneuvers with a 32-element monoplane transnasal
      transesophageal echocardiography probe to trace the atrial flow of the contrast
      agent in a 90 degrees bicaval view. A maneuver was rated positive when more than
      four bubbles appeared in the left atrium during the first three cardiac cycles
      after intrathoracic pressure release. The right atrial cross-sectional area
      before pressure release, and the peak septal excursion during atrial contrast
      opacification, were measured. McNemar's test was used to assess a paired
      dichotomous response on the two maneuvers for a significant difference. In 56
      patients, the ventilation maneuver was significantly (P < 0.037) more often
      positive for PFO (n = 14) than the Valsalva maneuver (n = 7). Although there was
      no difference in the methods regarding the peak septal excursion, the mean right
      atrial area before pressure release was significantly smaller during the
      ventilation maneuver than during the Valsalva maneuver (11.2 +/- 3.1 cm(2) vs
      14.4 +/- 3.3 cm(2), n = 42, P < 0.05). In the patients with a positive
      ventilation, but a negative Valsalva maneuver, the discrepancy was even larger
      (10.9 +/- 4.4 cm(2) vs 16.3 +/- 4.2 cm(2), n = 7, P < 0.001). We conclude that
      the ventilation maneuver is superior to the Valsalva maneuver in detecting PFO.
      Our data suggest that a peak pressure of 30 cm H(2)O during the ventilation
      maneuver achieves a more pronounced reduction in right atrial load and allows
      right atrial pressure to exceed left atrial pressure when intrathoracic pressure
      is released. IMPLICATIONS: A controlled ventilation maneuver in anesthetized
      patients immediately before posterior fossa surgery may be superior to the
      preoperative Valsalva maneuver in detecting a patent foramen ovale by contrast
      transesophageal echocardiography. This approach identifies patients at high risk
      for paradoxic embolism, but it is not practical for preoperative identification
      of patients who might benefit from patent foramen ovale closure before surgery.

PMID- 11323331
TI  - Do pulmonary artery catheters cause or increase tricuspid or pulmonic valvular
      regurgitation?
AB  - There are few quantitative data on the extent or mechanism of pulmonary artery
      catheter (PAC)-induced valvular dysfunction. We hypothesized that PACs cause or
      worsen tricuspid and pulmonic valvular regurgitation, and tested this hypothesis
      by using transesophageal echocardiography. In 54 anesthetized adult patients, we
      measured color Doppler jet areas of tricuspid regurgitation (TR) in two planes
      (midesophageal [ME] 4-chamber and right ventricular inflow-outflow views) and
      pulmonic insufficiency (PI) in one plane (ME aortic valve long-axis view), both
      before and after we advanced a PAC into the pulmonary artery. Regurgitant jet
      areas and hemodynamic measurements were compared by using paired t-test. There
      were no significant changes in blood pressure or heart rate after passage of the
      PAC. After PAC placement, the mean PI jet area was not significantly increased.
      The mean TR jet area increased significantly in the right ventricular inflow
      outflow view (+0.37 +/- 0.11 cm(2)) (P = 0.0014), but did not increase at the ME
      4-chamber view. Seventeen percent of patients had an increase in TR jet area > or
      =1 cm(2); 8% of patients had an increase in PI jet area >/=1 cm(2). IMPLICATIONS:
      In patients without pulmonic or tricuspid valvular pathology, placement of a
      pulmonary artery catheter (PAC) worsened tricuspid regurgitation, which is
      consistently visualized in the right ventricular inflow-outflow view, and often
      not seen in the midesophageal 4-chamber view. This is consistent with
      malcoaptation of the anterior and posterior leaflets. PAC-induced pulmonic
      insufficiency was rarely detected in the midesophageal aortic valve long-axis
      view. We conclude that a PAC is very unlikely to be the sole cause of severe
      tricuspid regurgitation or pulmonic insufficiency.

PMID- 11323332
TI  - Diagnosis by intraoperative transesophageal echocardiography of acute thrombosis
      of mechanical aortic valve prosthesis associated with the use of biological glue.
AB  - Mechanical aortic valve thrombosis is an uncommon complication of valve
      replacement. Inadequate anticoagulation is observed in 45% of patients presenting
      with this complication and it occurs as close as 15 days postoperation (1).
      Failure to wean from cardiopulmonary bypass (CPB) after aortic valve replacement
      may be because of a multitude of pathologies. We present a case where easy access
      to transesophageal echocardiography (TEE) allowed a rapid diagnosis of acute
      mechanical aortic valve occlusion with subsequent successful surgical management.

PMID- 11323333
TI  - The safety of intraoperative transesophageal echocardiography: a case series of
      7200 cardiac surgical patients.
AB  - Transesophageal echocardiography (TEE) is an invaluable intraoperative diagnostic
      monitor that is considered to be relatively safe and noninvasive. Insertion and
      manipulation of the TEE probe, however, may cause oropharyngeal, esophageal, or
      gastric trauma. We report the incidence of intraoperative TEE-associated
      complications in a single-center series of 7200 adult cardiac surgical patients.
      Information related to intraoperative TEE-associated complications was obtained
      retrospectively from the intraoperative TEE data form, routine postoperative
      visits, and cardiac surgical morbidity and mortality data. The overall incidences
      of TEE-associated morbidity and mortality in the study population were 0.2% and
      0%, respectively. The most common TEE-associated complication was severe
      odynophagia, which occurred in 0.1% of the study population. Other complications
      included dental injury (0.03%), endotracheal tube malpositioning (0.03%), upper
      gastrointestinal hemorrhage (0.03%), and esophageal perforation (0.01%). TEE
      probe insertion was unsuccessful or contraindicated in 0.18% and 0.5% of the
      study population, respectively. These data suggest that intraoperative TEE is a
      relatively safe diagnostic monitor for the management of cardiac surgical
      patients. IMPLICATIONS: The overall morbidity (0.2%) and mortality (0%) rates of
      intraoperative transesophageal echocardiography (TEE) were determined in a
      retrospective case series of 7200 adult, anesthetized cardiac surgical patients.
      The most common source of TEE-associated morbidity was odynophagia (0.1%), which
      resolved with conservative management. These results suggest that TEE is a safe
      diagnostic tool for the management of cardiac surgical patients.

PMID- 11323334
TI  - Plasma tranexamic acid concentrations during cardiopulmonary bypass.
AB  - Although tranexamic acid is used to reduce bleeding after cardiac surgery, there
      is large variation in the recommended dose, and few studies of plasma
      concentrations of the drug during cardiopulmonary bypass (CPB) have been
      performed. The plasma tranexamic acid concentration reported to inhibit
      fibrinolysis in vitro is 10 microg/mL. Twenty-one patients received an initial
      dose of 10 mg/kg given over 20 min followed by an infusion of 1 mg. kg(-1). h(-1)
      via a central venous catheter. Two patients were removed from the study secondary
      to protocol violation. Perioperative plasma tranexamic acid concentrations were
      measured with high-performance liquid chromatography. Plasma tranexamic acid
      concentrations (microg/mL; mean +/- SD [95% confidence interval]) were 37.4 +/-
      16.9 (45.5, 29.3) after bolus, 27.6 +/- 7.9 (31.4, 23.8) after 5 min on CPB, 31.4
      +/- 12.1 (37.2, 25.6) after 30 min on CPB, 29.2 +/- 9.0 (34.6, 23.8) after 60 min
      on CPB, 25.6 +/- 18.6 (35.1, 16.1) at discontinuation of tranexamic acid
      infusion, and 17.7 +/- 13.1 (24.1, 11.1) 1 h after discontinuation of tranexamic
      acid infusion. Four patients with renal insufficiency had increased
      concentrations of tranexamic acid at discontinuation of the drug. Repeated
      measures analysis revealed a significant main effect of abnormal creatinine
      concentration (P = 0.02) and time (P < 0.001) on plasma tranexamic acid
      concentration and a significant time x creatinine concentration interaction (P <
      0.001). IMPLICATIONS: A 10 mg/kg initial dose of tranexamic acid followed by an
      infusion of 1 mg.kg(-1).h(-1)produced plasma concentrations throughout the
      cardiopulmonary bypass period sufficient to inhibit fibrinolysis in vitro. The
      dosing of tranexamic acid may require adjustment for renal insufficiency.

PMID- 11323335
TI  - Debris elimination from partially-filled cell salvage bowls.

PMID- 11323336
TI  - Sevoflurane protects stunned myocardium through activation of mitochondrial ATP
      sensitive potassium channels.
AB  - We sought to determine the hemodynamic and cardioprotective effects of
      sevoflurane in canine stunned myocardium. Forty-nine dogs were allocated to one
      of seven groups (n = 7 for each). In six separate groups, dogs received vehicle,
      glibenclamide (a nonselective adenosine triphosphate-dependent potassium [K(ATP)]
      channel antagonist) (0.3 mg/kg IV) or 5-hydroxydecanoic acid (a mitochondrial
      K(ATP) channel antagonist) (5 mg/kg IV) in the presence or absence of 1 minimum
      alveolar concentration (1 MAC) sevoflurane. In an additional group, dogs received
      1 MAC sevoflurane with hemodynamic correction. Regional myocardial contractility
      was evaluated with segment shortening. Measurements were made before and during
      15-min ischemia and 90-min reperfusion. Recovery of segment shortening 90 min
      after reperfusion was significantly improved in the dogs anesthetized with
      sevoflurane either with or without hemodynamic correction (70.1 +/- 4.2 and 75.9
      +/- 3.1% of baseline, respectively), whereas the recovery was poor in control and
      glibenclamide or 5-hydroxydecanoic acid pretreated dogs (33.3 +/- 4.3, 33.8 +/-
      6.8, and 45.0 +/- 5.5% of baseline, respectively). Regional myocardial perfusion
      showed no significant difference among groups. The results indicate that
      sevoflurane has a cardioprotective effect mediated through activation of
      mitochondrial K(ATP) channels and independent of coronary blood flow or reduction
      in cardiac work. IMPLICATIONS: Sevoflurane exerts a cardioprotective effect that
      is mediated via activation of adenosine triphosphate-sensitive potassium channels
      in ischemic canine hearts.

PMID- 11323337
TI  - Can initial distribution volume of glucose predict hypovolemic hypotension after
      radical surgery for esophageal cancer?
AB  - We recently reported that the initial distribution volume of glucose (IDVG)
      reliably measures the central extracellular fluid volume in the presence or
      absence of fluid gain or loss. We examined which variables, including IDVG, can
      predict subsequent hypovolemic hypotension produced by the continuous shift of
      the extracellular fluid from the central to the peripheral compartment early
      after radical surgery for esophageal cancer. IDVG and plasma volume were
      calculated after measuring cardiac index (CI), central venous pressure, and
      pulmonary artery wedge pressure immediately after admission to the intensive care
      unit. Intraoperative fluid balance and urine volume were also recorded.
      Postoperative hypovolemic hypotension was clinically defined as systolic blood
      pressure < 80 mm Hg responsive to IV fluid administration. Either IDVG < 105
      mL/kg or CI < 3.4 L. min(-1). m(-2) was associated with subsequent hypovolemic
      hypotension (P = 0.002 for the former and P = 0.00 03 for the latter), while
      remaining variables were not. IDVG and CI were well correlated (r = 0.8 7, n =
      25, P = 0.0001). Our results suggest that IDVG can help predict the subsequent
      hypovolemic hypotension early after radical surgery for esophageal cancer.
      IMPLICATIONS: Routine cardiovascular variables immediately after major surgery
      cannot predict the subsequent hypovolemic hypotension produced by the shift of
      the extracellular fluid. Glucose dilution using glucose 5 g and a one-compartment
      model can predict it simply and rapidly.

PMID- 11323338
TI  - The safety and efficacy of sevoflurane anesthesia in infants and children with
      congenital heart disease.
AB  - We tested the hypothesis that sevoflurane is a safer and more effective
      anesthetic than halothane during the induction and maintenance of anesthesia for
      infants and children with congenital heart disease undergoing cardiac surgery.
      With a background of fentanyl (5 microg/kg bolus, then 5 microg. kg(-1). h(-1)),
      the two inhaled anesthetics were directly compared in a randomized, double
      blinded, open-label study involving 180 infants and children. Primary outcome
      variables included severe hypotension, bradycardia, and oxygen desaturation,
      defined as a 30% decrease in the resting mean arterial blood pressure or heart
      rate, or a 20% decrease in the resting arterial oxygen saturation, for at least
      30 s. There were no differences in the incidence of these variables; however,
      patients receiving halothane experienced twice as many episodes of severe
      hypotension as those who received sevoflurane (P = 0.03). These recurrences of
      hypotension occurred despite an increased incidence of vasopressor use in the
      halothane-treated patients than in the sevoflurane-treated patients. Multivariate
      stepwise logistic regression demonstrated that patients less than 1 yr old were
      at increased risk for hypotension compared with older children (P = 0.0004), and
      patients with preoperative cyanosis were at increased risk for developing severe
      desaturation (P = 0.049). Sevoflurane may have hemodynamic advantages over
      halothane in infants and children with congenital heart disease. IMPLICATIONS: In
      infants and children with congenital heart disease, anesthesia with sevoflurane
      may result in fewer episodes of severe hypotension and less emergent drug use
      than anesthesia with halothane.

PMID- 11323339
TI  - Continuous fascia iliaca compartment block in children: a prospective evaluation
      of plasma bupivacaine concentrations, pain scores, and side effects.
AB  - We sought to determine the plasma concentrations of bupivacaine and its main
      metabolite after continuous fascia iliaca compartment (FIC) block in children.
      Twenty children (9.9 +/- 4 yr, 38 +/- 19 kg) received a continuous FIC block for
      either postoperative analgesia (n = 16) or femoral shaft fracture (n = 4). A
      bolus dose of 0.25% bupivacaine (1.56 +/- 0.3 mg/kg) with epinephrine was
      followed by a continuous administration of 0.1% bupivacaine (0.135 +/- 0.03 mg.
      kg(-)(1). h(-)(1)) for 48 h. Plasma bupivacaine levels were determined at 24 h
      and 48 h by using gas liquid chromatography. Heart rate, arterial blood pressure,
      respiratory rate, side effects, and pain scores were recorded at 4-h intervals
      during 48 h. No significant differences were found between mean plasma
      bupivacaine levels at 24 h (0.71 +/- 0.4 microg/mL) and at 48 h (0.84 +/- 0.4
      microg/mL) (P = 0.33). FIC block provided adequate analgesia in most cases. No
      severe adverse effects were noted. We conclude that the bupivacaine plasma
      concentrations during continuous FIC block in children are within the safety
      margins. FIC block is well tolerated, and provides satisfactory pain relief in
      most cases. IMPLICATIONS: In this study, we have shown that, in children,
      continuous fascia iliaca compartment block, a technique providing neural blockade
      of the thigh and the anterior part of the knee, was associated with safe plasma
      bupivacaine concentrations, was well tolerated, and provided satisfactory pain
      scores in most cases.

PMID- 11323340
TI  - The effect of intranasal fentanyl on the emergence characteristics after
      sevoflurane anesthesia in children undergoing surgery for bilateral myringotomy
      tube placement.
AB  - Children undergoing placement of bilateral myringotomy tubes (BMT) often exhibit
      pain-related behavior (agitation) in the postanesthesia care unit. We compared
      the emergence and recovery profiles of pediatric patients who received
      sevoflurane with or without supplementary intranasal fentanyl for BMT surgery. By
      using a prospective, double-blinded design, 150 children 6 mo to 5 yr of age,
      scheduled for routine BMT surgery, were anesthetized with sevoflurane (2%-3%) in
      a 60% N(2)O/O(2) gas mixture. Patients were randomized to receive equal volumes
      of intranasal saline (Control), 1 microg/kg fentanyl or 2 microg/kg fentanyl. A
      blinded observer evaluated each patient using a previously described 4-point
      agitation scale and the Steward recovery scale. Response to parental presence was
      observed after a score of six (full recovery) was achieved on the Steward
      recovery scale. There were no significant differences among the three groups
      regarding age, weight, surgeon, duration of anesthesia, or ear condition.
      Recovery times and emergence characteristic scores were not statistically
      different. Agitation scores were significantly reduced in the 2-microg/kg
      Fentanyl group as compared with the Control group (P = 0.012). Fentanyl 2
      microg/kg is recommended to reduce the incidence of agitation seen in these
      patients. IMPLICATIONS: We examined the use of nasally administered fentanyl for
      the relief of agitation or discomfort after placement of bilateral myringotomy
      tubes in 150 children ages 6 mo to 5 yr using a prospective, double-blinded
      design. Fentanyl 2 microg/kg was found to reduce the incidence of agitation in
      these patients.

PMID- 11323341
TI  - Caudal epidural blood patch for treating intractable vomiting in a child after
      placement of a permanent intrathecal catheter.
AB  - Postdural puncture cerebral spinal fluid (CSF) leak most often manifests as a
      postdural puncture headache (PDPH). The reported frequency in young children
      varies (1-4). Persistent CSF leak may also be present without PDPH. We present a
      case of postoperative nausea and vomiting resulting from a presumed lumbar CSF
      leak in a nonverbal child after surgical placement of a permanent intrathecal
      catheter. Treatment with an epidural blood patch (EBP) via the caudal approach
      resulted in complete relief of symptoms.

PMID- 11323342
TI  - Rapacuronium: an alternative to succinylcholine for electroconvulsive therapy.

PMID- 11323343
TI  - Modulation of NMDA receptor function by ketamine and magnesium: Part I.
AB  - N-methyl-D-aspartate (NMDA) receptors are important components of pain
      processing. Ketamine and Mg2+ block NMDA receptors and might therefore be useful
      analgesics, and combinations of Mg2+ and ketamine provide more effective
      analgesia. We investigated their interactions at NMDA receptors. Xenopus oocytes,
      expressing NR1/NR2A or NR1/NR2B glutamate receptors, were studied. The effects of
      Mg2+, racemic ketamine and its isomers, and the combination of Mg2+ and S(+)
      ketamine on NMDA signaling were determined. Mg2+ and ketamine alone inhibited
      NMDA receptors noncompetitively (half-maximal inhibitory effect concentration:
      Mg2+ 4.2 +/- 1.2 x 10(-)(4) M at NR1/NR2A and 6.3 +/- 2.4 x 10(-)(4) M at
      NR1/NR2B; racemic ketamine 13.6 +/- 8.5 x 10(-)(6) M at NR1/NR2A and 17.6 +/- 7.2
      x 10(-)(6) M at NR1/NR2B; S(+)-ketamine 4.1 +/- 2.5 x 10(-)(6) at NR1/NR2A and
      3.0 +/- 0.3 at NR1/NR2B; R(-)-ketamine 24.4 +/- 4.1 x 10(-)(6) M at NR1/NR2A and
      26.0 +/- 2.4 x 10(-)(6) M at NR1/NR2B). The combined application of Mg2+ and
      ketamine decreased the half-maximal inhibitory effect concentration >90% at both
      receptors. Isobolographic analysis demonstrated super-additive interactions.
      Ketamine and Mg2+ inhibit responses of recombinantly expressed NR1/NR2A and
      NR1/NR2B glutamate receptors, and combinations of the compounds act in a super
      additive manner. These findings may explain, in part, why combinations of
      ketamine and Mg2+ are more effective analgesics than either compound alone.
      IMPLICATIONS: Ketamine and Mg2+ inhibit functioning of recombinantly expressed
      NR1/NR2A and NR1/NR2B glutamate receptors, and combinations of the compounds act
      in a super-additive manner. These findings may explain, in part, why combinations
      of ketamine and Mg2+ are more effective analgesics than either compound alone.

PMID- 11323345
TI  - Propofol blocks human skeletal muscle sodium channels in a voltage-dependent
      manner.
AB  - Propofol decreases muscle tone in the absence of neuromuscular blocking drugs.
      This effect probably cannot be attributed solely to central nervous depression.
      We studied the effects of propofol on heterologously expressed skeletal muscle
      sodium channels. Our hypothesis was that the decrease in muscle tone may partly
      be attributed to an interaction of propofol with sarcolemmal sodium channels.
      Cells were voltage clamped and whole-cell sodium inward currents were recorded in
      the absence and presence of propofol. When depolarizing pulses to 0 mV were
      started from a holding potential close to the normal resting potential of muscle
      (-70 mV), or when a 2.5-s prepulse inducing slow inactivation was applied before
      the test pulse at -100 mV, a significant reduction in the peak current amplitude
      was achieved by 10 and 5 microM propofol, respectively (P < 0.001). Half-maximum
      blocking concentrations with these protocols were 23 and 22 microM. Blocking
      potency increased at depolarized membrane potentials with the fraction of
      inactivated channels; the estimated dissociation constant K(d) from the
      inactivated state was 4.6 microM. These results suggest that propofol
      significantly blocks sarcolemmal sodium channels at clinically relevant
      concentrations while maintaining potentials close to the physiological resting
      potential. IMPLICATIONS: Voltage-gated sodium channels mediate the initiation and
      propagation of action potentials along the sarcolemma. Results from our study
      show that those channels are targeted and blocked in a concentration- and voltage
      dependent manner by propofol. This mechanism may contribute to the reduction in
      muscle excitability.

PMID- 11323344
TI  - Modulation of NMDA receptor function by ketamine and magnesium. Part II:
      interactions with volatile anesthetics.
AB  - Mg2+ and ketamine interact superadditively at N- methyl-D-aspartate (NMDA)
      receptors, which may explain the clinical efficacy of the combination. Because
      patients are usually exposed concomitantly to volatile anesthetics, we tested the
      hypothesis that volatile anesthetics interact with ketamine and/or Mg2+ at
      recombinantly expressed NMDA receptors. NR1/NR2A or NR1/NR2B receptors were
      expressed in Xenopus oocytes. We determined the effects of isoflurane,
      sevoflurane, and desflurane on NMDA receptor signaling, alone and in combination
      with S(+)-ketamine (4.1 microM on NR1/NR2A, 3.0 microM on NR2/NR2B) and/or Mg2+
      (416 microM on NR1/NR2A, 629 microM on NR1/NR2B). Volatile anesthetics inhibited
      NR1/NR2A and NR1/NR2B glutamate receptor function in a reversible, concentration
      dependent, voltage-insensitive and noncompetitive manner (half-maximal inhibitory
      concentration at NR1/NR2A receptors: 1.30 +/- 0.02 minimum alveolar anesthetic
      concentration [MAC] for isoflurane, 1.18 +/- 0.03 MAC for desflurane, 1.24 +/-
      0.06 MAC for sevoflurane; at NR1/NR2B receptors: 1.33 +/- 0.12 MAC for
      isoflurane, 1.22 +/- 0.08 MAC for desflurane, and 1.28 +/- 0.08 MAC for
      sevoflurane). On both NR1/NR2A and NR1/NR2B receptors, 50% inhibitory
      concentration for volatile anesthetics was reduced approximately 20% by Mg2+,
      approximately 30% by S(+)-ketamine, and approximately 50% by the compounds in
      combination. Volatile anesthetic effects on NMDA receptors can be potentiated
      significantly by Mg2+, S(+)-ketamine, or-most profoundly-both. Therefore, the
      analgesic effects of ketamine and Mg2+, are likely to be enhanced in the presence
      of volatile anesthetics. IMPLICATIONS: Clinically relevant concentrations of
      volatile anesthetics inhibit functioning of N-methyl-D-aspartate receptors
      expressed recombinantly in Xenopus oocytes. This inhibition is reversible,
      concentration-dependent and voltage-insensitive, and results from noncompetitive
      antagonism of glutamate/glycine signaling. In addition, these effects can be
      potentiated significantly by co-application of either Mg2+, S(+)-ketamine, or-
      most profoundly--both.

PMID- 11323346
TI  - Duration of action of vecuronium after an intubating dose of rapacuronium,
      vecuronium, or succinylcholine.
AB  - Rapacuronium (RAP) is a new, rapid-onset, short-duration, nondepolarizing
      neuromuscular blocker. If RAP is used to facilitate endotracheal intubation, what
      will the duration of a subsequent maintenance dose of vecuronium (VEC) be? We
      investigated the duration of action of a maintenance dose of VEC after intubation
      with RAP, VEC, or succinylcholine (SUC). Adult surgical patients under general
      anesthesia were randomly allocated to receive a tracheal intubating dose of RAP
      1.5 mg/kg, VEC 0.1 mg/kg, or SUC 1 mg/kg. The anesthetic was induced with
      propofol and maintained with propofol, nitrous oxide, and oxygen. Neuromuscular
      function was monitored with electromyography. Recovery of the intubating dose of
      neuromuscular blocker was allowed to occur spontaneously until the first twitch
      of the train-of-four (T1) reached 50% of baseline, and then VEC 0.025 mg/kg (0.5
      x 95% effective dose [ED(95)]) was administered. The onset, duration, and
      recovery to T1 = 25% and 50% were recorded. The durations of action (recovery of
      T1 25%) after intubating doses of RAP, VEC, and SUC were 13.7 +/- 5.3, 43.2 +/-
      13.2, and 9.2 +/- 3.7 min (mean +/- SD), respectively (P < 0.0001). The times to
      maximum depression of T1 after a maintenance dose of VEC (0.5 x ED(95)) were 5.4
      +/- 2.9, 5.1 +/- 2.5, and 5.3 +/- 2.8 min (mean +/- SD) for the RAP, VEC, and SUC
      groups, respectively. Recoveries to T1 25% after VEC for the RAP, VEC, and SUC
      groups were 18.9 +/- 11.5, 21.5 +/- 8.03, and 12.8 +/- 8.4 min, and at T1 50%
      they were 21.5 +/- 9.1, 30.8 +/- 9.5, and 15.5 +/- 9.7 min (mean +/- SD),
      respectively (P < 0.001, RAP and VEC versus SUC). The duration of action of a
      maintenance dose of VEC was similar after an intubating dose of RAP or VEC but
      was shortened when preceded by an intubating dose of SUC. IMPLICATIONS: The
      duration of action of a maintenance dose of vecuronium was longer after an
      endotracheal intubating dose of rapacuronium compared with succinylcholine.

PMID- 11323347
TI  - The use of an anesthesia information management system for prediction of
      antiemetic rescue treatment at the postanesthesia care unit.
AB  - We used an anesthesia information management system (AIMS) to devise a score for
      predicting antiemetic rescue treatment as an indicator for postoperative nausea
      and vomiting (PONV) in the postanesthesia care unit (PACU). Furthermore, we
      wanted to investigate whether data collected with an AIMS are suitable for
      comparable clinical investigations. Over a 3-yr period (January 1, 1997, to
      December 31, 1999), data sets of 27,626 patients who were admitted
      postoperatively to the PACU were recorded online by using the automated
      anesthesia record keeping system NarkoData(R) (IMESO GmbH, Huttenberg, Germany).
      Ten patient-related, 5 operative, 15 anesthesia-related, and 4 postoperative
      variables were studied by using forward stepwise logistic regression. Not only
      can the probability of having PONV in the PACU be estimated from the 3 previously
      described patient-related (female gender, odds ratio [OR] = 2.45; smoker, OR =
      0.53; and age, OR = 0.995) and one operative variables (duration of surgery, OR =
      1.005), but 3 anesthesia-related variables (intraoperative use of opioids, OR =
      4.18; use of N(2)O, OR = 2.24; and IV anesthesia with propofol, OR = 0.40) are
      predictive. In implementing an equation for risk calculation into the AIMS, the
      individual risk of PONV can be calculated automatically. IMPLICATIONS: The aim of
      this study was to investigate predictors for postoperative nausea and vomiting by
      using online anesthesia records. With the help of computerized data evaluation, 7
      of 34 variables could be detected as risk factors. By implementing an automatic
      score into the record keeping system, an individual risk calculation could be
      made possible.

PMID- 11323349
TI  - The impact on revenue of increasing patient volume at surgical suites with
      relatively high operating room utilization.
AB  - We previously studied hospitals in the United States of America that are losing
      money despite limiting the hours that operating room (OR) staff are available to
      care for patients undergoing elective surgery. These hospitals routinely keep
      utilization relatively high to maximize revenue. We tested, using discrete-event
      computer simulation, whether increasing patient volume while being reimbursed
      less for each additional patient can reliably achieve an increase in revenue when
      initial adjusted OR utilization is 90%. We found that increasing the volume of
      referred patients by the amount expected to fill the surgical suite (100%/90%)
      would increase utilization by <1% for a hospital surgical suite (with longer
      duration cases) and 4% for an ambulatory surgery suite (with short cases). The
      increase in patient volume would result in longer patient waiting times for
      surgery and more patients leaving the surgical queue. With a 15% reduction in
      payment for the new patients, the increase in volume may not increase revenue and
      can even decrease the contribution margin for the hospital surgical suite. The
      implication is that for hospitals with a relatively high OR utilization, signing
      discounted contracts to increase patient volume by the amount expected to "fill"
      the OR can have the net effect of decreasing the contribution margin (i.e.,
      profitability). IMPLICATIONS: Hospitals may try to attract new surgical volume by
      offering discounted rates. For hospitals with a relatively high operating room
      utilization (e.g., 90%), computer simulations predict that increasing patient
      volume by the amount expected to "fill" the operating room can have the net
      effect of decreasing contribution margin (i.e., profitability).

PMID- 11323348
TI  - Auditory information processing during adequate propofol anesthesia monitored by
      electroencephalogram bispectral index.
AB  - Memory for intraoperative events may arise from inadequate anesthesia when the
      hypnotic state is not continuously monitored. Electroencephalogram bispectral
      index (BIS) enables monitoring of the hypnotic state and titration of anesthesia
      to an adequate level (BIS 40 to 60). At this level, preserved memory function has
      been observed in trauma patients. We investigated memory formation in elective
      surgical outpatients during target-controlled propofol anesthesia supplemented
      with alfentanil. While BIS remained between 40 and 60, patients listened to a
      tape with either familiar instances (exemplars) from two categories (Experimental
      [E] group, n = 41) or bird sounds (Control [C] group, n = 41). After recovery,
      memory was tested directly and indirectly. BIS during audio presentation was on
      average (+/- SD) 44 +/- 5 and 46 +/- 5 for Groups E and C, respectively. No
      patient consciously recalled the intraoperative period, nor were presented words
      recognized reliably (Group E, 0.9 +/- 0.8 hits; Group C, 0.8 +/- 0.8 hits) (P =
      0.7). When asked to generate category exemplars, Group E named 2.10 +/- 1.0 hits
      versus 1.98 +/- 1.0 in Group C (P = 0.9). We found no explicit or implicit memory
      effect of familiar words presented during adequate propofol anesthesia at BIS
      levels between 40 and 60 in elective surgical patients. IMPLICATIONS: This study
      suggests that stable levels of adequate hypnosis may prevent information
      processing and memory formation during general anesthesia and supports the
      feasibility of electroencephalogram bispectral index as a monitor of adequate
      anesthesia.

PMID- 11323350
TI  - Statistical analysis by Monte-Carlo simulation of the impact of administrative
      and medical delays in discharge from the postanesthesia care unit on total
      patient care hours.

PMID- 11323351
TI  - The effects of prone positioning on intraabdominal pressure and cardiovascular
      and renal function in patients with acute lung injury.
AB  - To detect any harmful effects of prone positioning on intraabdominal pressure
      (IAP) and cardiovascular and renal function, we studied 16 mechanically
      ventilated patients with acute lung injury randomly in prone and supine
      positions, without minimizing the restriction of the abdomen. Effective renal
      blood flow index and glomerular filtration rate index were determined by the
      paraaminohippurate and inulin clearance techniques. Prone positioning resulted in
      an increase in IAP from 12 +/- 4 to 14 +/- 5 mm Hg (P < 0.05), PaO(2)/fraction of
      inspired oxygen from 220 +/- 91 to 267 +/- 82 mm Hg (P < 0.05), cardiac index
      from 4.1 +/- 1.1 to 4.4 +/- 0.7 L/min (P < 0.05), mean arterial pressure from 77
      +/- 10 to 82 +/- 11 mm Hg (P < 0.01), and oxygen delivery index from 600 +/- 156
      to 648 +/- 95 mL. min(-)(1). m(-)(2) (P < 0.05). Renal fraction of cardiac output
      decreased from 19.1% +/- 12.5% to 15.5% +/- 8.8% (P < 0.05), and renal vascular
      resistance index increased from 11762 +/- 6554 dynes. s. cm(-)(5). m(2) to 15078
      +/- 10594 dynes. s. cm(-)(5). m(2) (P < 0.05), whereas effective renal blood flow
      index, glomerular filtration rate index, filtration fraction, urine volume,
      fractional sodium excretion, and osmolar and free water clearances remained
      constant during prone positioning. Prone positioning, when used in patients with
      acute lung injury, although it is associated with a small increase in IAP,
      contributes to improved arterial oxygenation and systemic blood flow without
      affecting renal perfusion and function. Apparently, special support to allow free
      chest and abdominal movement seems unnecessary when mechanically ventilated,
      hemodynamically stable patients without abdominal hypertension are proned to
      improve gas exchange. IMPLICATIONS: Prone positioning is increasingly used to
      improve gas exchange in patients with acute lung injury. However, during prone
      positioning an increase in intraabdominal pressure in these critically ill
      patients may promote dysfunction of other organs. Therefore, we performed a
      randomized study in mechanically ventilated patients with acute lung injury to
      investigate the cardiovascular and renal effects of prone positioning.

PMID- 11323352
TI  - Prolonged sedation with propofol in the rat does not result in sleep deprivation.
AB  - The use of propofol provides sedation without prolonging emergence in patients in
      the Intensive Care Unit. When prolonged, however, continuous sedation may overlap
      with naturally occurring sleep periods and potentially increase the risk of sleep
      deprivation. We modified an established rat model of sleep to determine whether
      prolonged, continuous sedation results in sleep deprivation. Rats were
      continuously sedated for a 12-h period overlapping completely with their normal
      sleep phase. Electroencephalogram (EEG) and movement data were collected before
      and after the sedation period. Rats were evaluated for EEG and movement evidence
      of sleep deprivation after sedation. When compared with baseline, the time spent
      in rapid eye movement (REM) and non-REM sleep was decreased during the first 4 h
      after sedation. The duration of non-REM sleep bouts was not altered. Power in the
      delta band (0.5-4 Hz) during non-REM sleep was diminished during the first 2 h
      only. Movements were reduced during the first hour after emergence from sedation
      only. In summary, no EEG or behavioral evidence of sleep deprivation was observed
      on emergence from sedation. These results imply that sedation is associated with
      a restorative process reversing the natural accumulation of sleep need that
      occurs during wakefulness. IMPLICATIONS: Prolonged sedation in the Intensive Care
      Unit may alter the restorative effects of naturally occurring sleep. We sedated
      rats during their sleep phase to determine whether sedation interferes with
      sleep. Upon emergence, no evidence of sleep deprivation was observed. Sedation
      may thus be associated with a restorative effect similar to sleep.

PMID- 11323353
TI  - The effects of FK506 on neurologic and histopathologic outcome after transient
      spinal cord ischemia induced by aortic cross-clamping in rats.
AB  - Spinal cord injury is a devastating complication of thoracoabdominal aortic
      surgery. We investigated the effect of the immunosuppressant FK506, a macrolide
      antibiotic demonstrated to have neuroprotective effects in cerebral ischemia
      models, in a rat model of transient spinal cord ischemia. Spinal cord ischemia
      was induced in anesthetized rats by using direct aortic arch plus left subclavian
      artery cross-clamping through a limited thoracotomy. Experimental groups were as
      follows: sham-operation; control, receiving only vehicle; FK506 A, receiving
      FK506 (1 mg/kg IV) before clamping; and FK506 B, receiving FK506 (1 mg/kg IV) at
      the onset of reperfusion. Neurologic status was assessed at 24 h and then daily
      up to 96 h with a 0 to 6 scale (0, normal function; 6, severe paraplegia). Rats
      were randomly killed at 24, 48, or 96 h, and spinal cords were harvested for
      histopathology. Physiologic variables did not differ significantly among
      experimental groups. All control rats suffered severe and definitive paraplegia.
      FK506-treated rats had significantly better neurologic outcome compared with
      control. Histopathologic analysis disclosed severe injury in the lumbar gray
      matter of all control rats, whereas most FK506-treated rats had less injury.
      These data suggest that FK506 can improve neurologic recovery and attenuate
      spinal cord injury induced by transient thoracic aortic cross-clamping.
      IMPLICATIONS: A single dose-injection of the immunosuppressant FK506
      significantly improved neurologic outcome and attenuated spinal cord injury
      induced by transient thoracic aortic cross-clamping in the rat.

PMID- 11323354
TI  - The effects of 30% and 60% xenon inhalation on pial vessel diameter and
      intracranial pressure in rabbits.
AB  - Xenon may increase cerebral blood flow and intracranial pressure (ICP). To
      evaluate the effects of xenon on brain circulation, we measured pial vessel
      diameter changes, CO(2) reactivity, and ICP during xenon inhalation in rabbits.
      Minimum alveolar anesthetic concentration (MAC) for xenon was established in
      rabbits (n = 6). By using a cranial window model, pial vessel diameters were
      measured at 30% and 60% xenon inhalation and in time control groups (n = 15).
      ICP, mean arterial blood pressure, and heart rate were recorded during 30% and
      60% xenon inhalation (n = 5). Pial vessel diameters were measured during
      hypocapnia and hypercapnia conditions in 60% Xenon and Control groups (n = 14).
      MAC for xenon was 85%. Xenon (0.35 and 0.7 MAC) dilated the arterioles (10% and
      18%, respectively) and venules (2% and 4%, respectively) (P < 0.05). Dilation of
      arterioles was more prominent than that of venules. ICP, mean arterial blood
      pressure, and heart rate did not change during xenon inhalation. No difference in
      CO(2) reactivity was observed between Xenon and Control groups (P = 0.79). Sixty
      percent xenon (0.7 MAC) dilated brain vessels, but venule changes were small.
      Xenon did not increase ICP and preserved CO(2) reactivity of the brain vessels.
      IMPLICATIONS: Xenon might increase cerebral blood flow; however, 0.7 minimum
      alveolar anesthetic concentration xenon preserved both low intracranial pressure
      and CO(2) reactivity of the cerebral vessels in the normal rabbit.

PMID- 11323355
TI  - The use of dexmedetomidine infusion for awake craniotomy.

PMID- 11323356
TI  - Acute transverse myelopathy after posterior cervical decompressive laminectomy
      and fusion.

PMID- 11323357
TI  - The effect of magnesium on coagulation in parturients with preeclampsia.
AB  - Preeclampsia is associated with complex coagulation abnormalities that include
      altered platelet function and consumption and activation of the fibrinolytic
      system. Magnesium sulfate, which is used as a therapeutic modality for the
      prevention of seizures in preeclamptic parturients, has anticoagulant and
      antiplatelet effects. We sought to determine the effects of magnesium on various
      components of the coagulation system in patients with preeclampsia. We assessed
      the coagulation status of 18 parturients with preeclampsia being treated with
      magnesium. The assessment was performed with the thromboelastograph test, which
      provides an overall assessment of blood coagulation via the coagulation index.
      Thromboelastography was performed before beginning magnesium therapy and 30 min
      and 2 h after a 6-g bolus of IV magnesium. The R value (time to first clot
      formation) was found to be significantly slower (P < 0.05) at 30 min after the
      magnesium bolus. This result suggests increased coagulant factor activity
      resulting from the magnesium bolus. However, there was no effect of magnesium on
      the overall coagulation, as evidenced by the lack of change in the coagulation
      index either at 30 min or at 2 h after the completion of the initial magnesium
      bolus. Therefore, this therapy should have no effect on the use of neuraxial
      techniques. IMPLICATIONS: On the basis of the thromboelastography assessment, we
      found that the current practice of administering magnesium did not influence
      overall coagulation in preeclamptic women. Therefore, magnesium administration
      should not affect the use of neuraxial techniques.

PMID- 11323358
TI  - A comparison of 0.0625% bupivacaine with fentanyl and 0.1% ropivacaine with
      fentanyl for continuous epidural labor analgesia.
AB  - We compared the analgesic efficacy and the degree of motor block achieved with
      epidural infusion of 0.0625% bupivacaine (Group B) versus 0.1% ropivacaine (Group
      R), both with 0.0002% fentanyl (2 microg/mL) in laboring patients. A prospective,
      double-blinded study was performed in 98 ASA physical status I-II parturients who
      were divided randomly into two groups to receive either bupivacaine or
      ropivacaine after catheter location had been tested with an initial bolus of
      lidocaine and fentanyl. The infusion rate was 15 mL/h in every case. When pain
      was perceived, 5-mL boluses of the assigned epidural analgesic were administered
      every 10 min until analgesia was achieved. We recorded pain intensity, level of
      sensory block, degree of motor block, hemodynamic variables, secondary effects,
      mode of delivery, neonatal outcome, and patient satisfaction. There were no
      statistically significant differences in any of the factors analyzed. Highly
      effective analgesia was achieved in both groups with a small incidence of motor
      block. These findings suggest that bupivacaine may be more potent than
      ropivacaine. IMPLICATIONS: We compared different concentrations of epidural
      bupivacaine and ropivacaine thought to be equipotent. Both solutions were equally
      efficient in providing highly effective epidural analgesia for labor with minimal
      motor block. These findings suggest that bupivacaine may be more potent than
      ropivacaine.

PMID- 11323359
TI  - Obstetric anesthetic management of a parturient with Larsen syndrome and short
      stature.

PMID- 11323360
TI  - Perioperative care of a patient with acute fatty liver of pregnancy.
AB  - Acute fatty liver of pregnancy (AFLP) is a late gestational complication with
      biochemical similarities to the inherited disorders of mitochondrial fatty acid
      oxidation and clinical similarities to fulminant hepatic failure. The following
      case illustrates our perioperative management of this rarely encountered
      disorder.

PMID- 11323361
TI  - Ultrasonographic findings of the axillary part of the brachial plexus.
AB  - In this prospective study we sought to determine anatomic variations of the main
      brachial plexus nerves in the axilla and upper arm via high-resolution
      ultrasonography (US) examination. Positions of nerves were studied via US in
      three sectional levels of the upper arm in 69 healthy volunteers (31 men and 38
      women, median age 28 yr). Analysis was done by subdividing the US picture into
      eight pie-chart sectors and matching sectors for the position of the ulnar,
      radial, and median nerves. Shortly after the nerves pass the pectoralis minor
      muscle, they begin to diverge. At the middle level 9%-13%, and at the distal
      level, 30%-81% of the nerves are not seen together with the artery in the US
      picture. At the usual level of axillary block approach, we found the ulnar nerve
      in the posterior medial position in 59% of the volunteers. The other two nerves
      had two peaks in distribution: the radial nerve in posterior lateral (38%) and
      anterior lateral (20%) position, and the median nerve in anterior medial (30%)
      and posterior medial (26%) position. Applying light pressure distally can
      displace nerves to the side, especially when they are positioned anterior to the
      axillary artery. We conclude that an axillary block should be attempted as
      proximal as possible to the axilla. IMPLICATIONS: This prospective
      ultrasonography study demonstrates significant anatomic variations of the main
      brachial plexus nerves in the axilla and upper arm, which may increase the
      difficulty in identifying neural structures. Applying light pressure on the
      plexus can move nerves to the side, especially when they are positioned anterior
      to the axillary artery.

PMID- 11323362
TI  - Prolonged epidural infusions of ropivacaine (2 mg/mL) after colonic surgery: the
      impact of adding fentanyl.
AB  - We evaluated the safety and efficacy of a 72-h epidural infusion of ropivacaine
      and measured the impact of adding fentanyl 2 microg/mL to the required infusion
      rate, on the quality of postoperative pain relief and the incidence of side
      effects, after colonic surgery. One hundred fifty-five patients scheduled for
      elective colonic surgery were randomized in this trial. Epidural infusions of
      ropivacaine 2 mg/mL with fentanyl 2 microg/mL (R + F) and without fentanyl (R)
      were commenced during surgery and continued for 72 h postoperatively. This was a
      prospective, randomized, double-blinded, multi-center trial. The median infusion
      rate required was less in the R + F group (9.3 vs 11.5 mL/h, P < 0.001). Median
      pain scores at rest and on coughing were lower in the R + F group (P < 0.0001).
      The incidence of hypotension was more in the R + F group (P = 0.01). Time to
      readiness for discharge was delayed in the R + F group (median 6.6 vs 5.5 days, P
      = 0.012). The addition of fentanyl to ropivacaine resulted in decreased infusion
      rates and enhanced pain control; however, adverse effects were increased and
      readiness to discharge was delayed. IMPLICATIONS: Epidural infusions of
      ropivacaine with and without fentanyl were administered to patients to control
      pain after colonic surgery. Patients who received ropivacaine with fentanyl had
      better pain control, increased side effects, and delayed readiness to discharge.
      This study questions the value of adding opioids to epidural infusions of local
      anesthetics.

PMID- 11323363
TI  - Preoperative small-dose ketamine prevented tourniquet-induced arterial pressure
      increase in orthopedic patients under general anesthesia.
AB  - The mechanism of tourniquet-induced arterial pressure increase is not known. We
      investigated the effect of preoperative ketamine on tourniquet-induced arterial
      pressure and heart rate changes in 85 patients undergoing knee surgery with a
      tourniquet under general anesthesia. Patients were randomly assigned into three
      groups; Large Ketamine (n = 28; ketamine 1.0 mg/kg), Small Ketamine (n = 28;
      ketamine 0.25 mg/kg), and Control (n = 29; normal saline) groups. Anesthesia was
      maintained with 1.5%-2.5% sevoflurane and 66% N(2)O in oxygen with endotracheal
      intubation. Ketamine or normal saline was given in a double-blinded fashion
      before skin incision and tourniquet inflation. Arterial pressure and heart rate
      were recorded every 10 min until 60 min after the start of tourniquet inflation
      and again after deflation. Arterial pressure and heart rate were compared among
      the three groups by using repeated-measures analysis of variance. In the Large
      and Small Ketamine groups, arterial pressure was not significantly changed, but
      in the Control group arterial pressure was significantly increased 40, 50, and 60
      min after the start of tourniquet inflation (P < 0.05). Development of more than
      a 30% increase in systolic arterial pressure during tourniquet inflation was more
      frequent in the Control group than the other groups. The results show that
      preoperative IV ketamine, 0.25 mg/kg or more, significantly prevented tourniquet
      induced systemic arterial pressure increase in patients under general anesthesia.
      IMPLICATIONS: Preoperative small-dose ketamine, IV, significantly prevented a
      systemic arterial pressure increase during prolonged tourniquet inflation in
      patients under general anesthesia.

PMID- 11323364
TI  - Small-dose S(+)-ketamine reduces postoperative pain when applied with ropivacaine
      in epidural anesthesia for total knee arthroplasty.
AB  - Reduction of nociceptive input through blockade of N-methyl-D-aspartate (NMDA)
      receptors has been reported. We compared the effects of epidural S(+)-ketamine
      versus placebo on postoperative pain in a randomized, double-blinded study in 37
      patients undergoing unilateral knee arthroplasty. After lumbar epidural
      anesthesia with ropivacaine (10 mg/mL, 10-20 mL), 19 patients received 0.9%
      epidural saline, and 18 patients received 0.25 mg/kg epidural S(+)-ketamine 10
      min before surgical incision. After surgery, patient-controlled epidural
      analgesia with ropivacaine was provided. During the first 8 h after surgery,
      visual analog scale pain rating was similar between groups. Twenty-four and 48 h
      after surgery, patients anesthetized with ropivacaine had higher visual analog
      scale ratings at rest and during movement (P < 0.05) than patients anesthetized
      with S(+)-ketamine and ropivacaine. Forty-eight hours after surgery, patients
      anesthetized with ropivacaine also consumed more ropivacaine (558 +/- 210 mg) (P
      < 0.01) than those anesthetized with S(+)-ketamine and ropivacaine (319 +/- 204
      mg). Adverse events were similar between groups. Patients who received S(+)
      ketamine and ropivacaine rated the quality of their pain therapy better than
      those who received ropivacaine alone (P < 0.05). We conclude that the combination
      of S(+)-ketamine and ropivacaine in epidural anesthesia increases postoperative
      pain relief when compared with ropivacaine. IMPLICATIONS: Epidural S(+)-ketamine
      applied with ropivacaine before surgery is a rational approach to decrease injury
      induced pain sensitization. Epidural blockade with an N-methyl-D-aspartate
      receptor antagonist and a local anesthetic may provide better analgesia in the
      postoperative period than a local anesthetic alone.

PMID- 11323365
TI  - Can inflammatory pain prevent the development of acute tolerance to alfentanil?
AB  - Constant pain could, in principle, counteract mobilization of antianalgesia
      systems and prevent the development of acute tolerance to the analgesic effects
      of opioids. We sought to determine whether a tonic nociceptive input caused by
      inflammation inhibits the development of acute tolerance to alfentanil. The
      inflammation was induced by injection of carrageenan into the rat hind paw. A
      threshold of motor response to increasing pressure on the paw was used to
      determine analgesia. Alfentanil was administered IV with an infusion algorithm
      designed to maintain a constant plasma level of opioid for 4 h. The degree of
      acute tolerance was determined on the basis of decline in the level of analgesia.
      The continuous decline of the analgesic effect from its peak at 30 min to the end
      of the 4-h infusion period was profound, despite the constant-rate infusion of
      alfentanil. The degrees of decline were very similar in rats with and without
      carrageenan-induced inflammation (from 242 +/- 31 to 154 +/- 20 g, P < 0.0001;
      and from 242 +/- 33 to 148 +/- 14 g, P < 0.0001, respectively). The results
      suggest that inflammatory nociceptive input does not prevent the development of
      acute tolerance to opioid-induced analgesia measured as an increased reaction
      threshold to painful pressure. We conclude that acute tolerance to the analgesic
      effect of opioids is profound and develops very rapidly, even in the presence of
      constant nociceptive input. IMPLICATIONS: We examined whether inflammatory pain
      can prevent the rapid decline in analgesic effectiveness (acute tolerance) of
      alfentanil during its IV infusion. We found that acute tolerance to the analgesic
      effect of alfentanil, in the presence of constant pain caused by inflammation,
      develops as rapidly as without it.

PMID- 11323366
TI  - Inhibition of synovial plasma extravasation by preemptive administration of an
      antiinflammatory irrigation solution in the rat knee.
AB  - Inflammation and hyperalgesia during surgical procedures are caused by the local
      release of multiple inflammatory mediators. We used a rat knee joint model of
      acute inflammation (synovial plasma extravasation) to determine whether
      preemptive intraarticular irrigation of the antiinflammatory drugs ketoprofen,
      amitriptyline, or oxymetazoline, alone or in combination, can reduce inflammatory
      soup-induced plasma extravasation. These three drugs were selected because of
      their abilities to collectively inhibit the inflammatory effects of biogenic
      amines, eicosanoid production, and the release of neuropeptides from C-fiber
      terminals. Synovial perfusion of each one of the three drugs 10 min before, and
      then in combination with, the inflammatory soup (bradykinin, 5-hydroxytryptamine,
      and mustard oil) did not reduce plasma extravasation. Similarly, two-drug
      combinations did not significantly reduce inflammatory soup-induced plasma
      extravasation. The combination of all three drugs (amitriptyline, ketoprofen, and
      oxymetazoline) produced a dramatic inhibition of plasma extravasation and was
      more effective than any of the two-drug combinations. A comparison between the
      preemptive (10 min before inflammatory soup perfusion) and postinflammatory
      administration (10 min after inflammatory soup perfusion) showed that the
      postinflammatory administration of the three-drug solution lost all ability to
      inhibit inflammatory soup-induced plasma extravasation. We conclude that acute
      synovial inflammation, which is induced and maintained by multiple mediators, can
      be substantially inhibited only by the preemptive administration of a drug
      combination that targets multiple inflammatory mediators. IMPLICATIONS:
      Preemptive, intraarticular irrigation of a combination of multiple
      antiinflammatory drugs is a novel and potentially effective method for reducing
      the synovial inflammatory response, such as that during arthroscopy. In this
      study, a three-drug combination infusion was statistically superior to one- or
      two-drug infusions in a rat model.

PMID- 11323367
TI  - The antinociceptive and sedative effects of carbachol and oxycodone administered
      into brainstem pontine reticular formation and spinal subarachnoid space in rats.
AB  - To clarify the supraspinal and spinal actions of a cholinergic agonist,
      carbachol, and an opioid, oxycodone, we studied their antinociceptive and
      behavioral effects when administered into brainstem medial pontine reticular
      formation (mPRF) or spinal subarachnoid space with or without pretreatment of
      muscarinic receptor subtype antagonist. Sprague-Dawley rats were implanted with a
      24-gauge stainless steel guide cannula into the mPRF and chronically implanted
      with a lumbar intrathecal catheter. Antinociception was tested using tail flick
      latency, motor coordination was evaluated by the rotarod test, and overt sedation
      was assessed using a behavioral checklist. Carbachol (0.5-4.0 microg)
      administered into the mPRF produced significant dose- and time-dependent
      antinociception, sedation, and motor dysfunction. These were completely blocked
      by pretreatment with atropine and the M(2) muscarinic antagonist, methoctramine,
      and partially blocked by pretreatment with M(1) pirenzepine but not with M(3) p
      fHHSID: Oxycodone administered into the mPRF did not produce such effects. Spinal
      carbachol and oxycodone produced antinociception without any behavioral effects;
      their antinociceptive effects were completely blocked by pretreatment with
      atropine and M(2) antagonist. These results suggest that the antinociceptive
      action of carbachol is mediated by muscarinic cholinergic receptor activation,
      especially by M(2) receptor subtype in mPRF and spinal cord, and that although
      oxycodone seems unlikely to affect the cholinergic transmission of mPRF, spinal
      oxycodone-induced analgesia is at least partly mediated via the activation of
      M(2) receptor subtype at the spinal cord. IMPLICATIONS: Carbachol-induced
      antinociception and sedation is mediated with the activation of M(2) muscarinic
      receptors. Oxycodone administered into brainstem medial pontine reticular
      formation did not cause any antinociceptive or behavioral effects, but its spinal
      administration produced a significant antinociception via M(2) muscarinic
      receptor activation

PMID- 11323368
TI  - Reversible paraplegia associated with lumbar epidural analgesia and thoracic
      vertebral metastasis.

PMID- 11323369
TI  - The analgesic efficacy of tramadol is impaired by concurrent administration of
      ondansetron.
AB  - Tramadol has weak opioid properties, and an analgesic effect that is mediated
      mainly by inhibition of the reuptake of norepinephrine and serotonin (5
      hydroxytryptamine [5-HT]) and facilitation of 5-HT release (1,2) at the spinal
      cord. Because 5-HT3 receptors play a key role in pain transmission at the spinal
      level (3), the 5-HT3 antagonist ondansetron may decrease the efficacy of
      tramadol, as suggested in an abstract by Maroof et al. In that study, a small
      dose of 1 mg/kg tramadol was administered along with ondansetron 0.1 mg/kg or
      placebo, 15 min before the induction of anesthesia. Early postoperative pain
      scored differed significantly between the test groups. We therefore tested the
      hypothesis that the tramadol requirement by patient-controlled analgesia (PCA)
      may be increased when ondansetron is administered for antiemetic prophylaxis.

PMID- 11323370
TI  - Surgical stress induces endotoxin hyporesponsiveness and an early decrease of
      monocyte mCD14 and HLA-DR expression during surgery.
AB  - It is generally accepted that major surgery is associated with severe alterations
      of the host-defense mechanisms. We investigated the effect of surgical stress on
      the immune system. Specifically, we studied the relationship between
      perioperative lipopolysaccharide (LPS) hyporesponsiveness and monocyte human
      leukocyte antigen-DR (HLA-DR) and CD14 expression during the perioperative period
      in 20 patients who underwent partial gastrectomy. This study demonstrated that
      surgical stress rapidly depressed monocyte mCD14 and HLA-DR expression in
      comparison with preanesthesia levels. Monocyte mCD14 expression recovered to
      preoperative levels on the first postoperative day, and monocyte HLA-DR
      expression recovered by the seventh postoperative day. Consistent with our
      previous study, LPS-induced tumor necrosis factor (TNF)-alpha production ex vivo
      was significantly suppressed from the beginning of the operation. On the
      contrary, the plasma interleukin-10 concentration started to increase after the
      surgical incision was made. LPS hyporesponsiveness was least at the end of the
      operation and returned to preoperative levels on the first postoperative day. In
      conclusion, the present study demonstrated that LPS responsiveness, plasma
      interleukin-10 concentration, and monocytes mCD14 and HLA-DR expression altered
      from the early period of surgery. These alterations may be related to the
      impairment of the immune system during the perioperative period. IMPLICATIONS:
      Recent studies demonstrate that surgical stress induces immune dysfunction. We
      found that surgical stress rapidly decreased monocyte mCD14 and human leukocyte
      antigen-DR expression, and endotoxin responsiveness. These findings suggest that
      early changes of the immune system caused by surgical stress contribute to
      postoperative complications such as sepsis and multiple organ failure.

PMID- 11323371
TI  - The effects of diltiazem on hemodynamics and seizure duration during
      electroconvulsive therapy.
AB  - Electroconvulsive therapy (ECT) is often associated with acute hyperdynamic
      responses, and we hypothesize that diltiazem can blunt this response. We measured
      the effect of a 10-mg dose of diltiazem on heart rate and mean arterial pressure
      during ECT. Furthermore, we assessed seizure duration by using both the cuff
      method and two-lead electroencephalogram. We studied 18 patients with a
      randomized, double-blinded, placebo-controlled cross-over study design. Diltiazem
      significantly reduced heart rate and mean arterial pressure just after
      medication, and it also significantly reduced the increases in these variables
      after ECT, as compared with the placebo. The use of diltiazem was, however,
      associated with a shortened seizure duration, possibly making ECT less effective.
      Because of the reduction in seizure duration, the routine administration of
      diltiazem may not be advisable because it can possibly interfere with the
      psychotherapeutic efficacy of ECT. However, diltiazem medication for ECT is
      potentially useful for reducing tachycardia and hypertension in high-risk
      patients. IMPLICATIONS: Diltiazem can blunt acute hyperdynamic responses after
      electroconvulsive therapy, but seizure duration is also significantly reduced,
      possibly making this therapy less effective.

PMID- 11323372
TI  - The disposition of the cervical spine and deformation of available cord space
      with conventional- and balloon laryngoscopy-guided laryngeal intubation: a
      comparative study.
AB  - Orotracheal intubation causes cervical spine (C-spine) extension and potential
      (hypothetical) space available for the cord (SAC)-deformation. In the present
      study, we determined and compared the changes induced by conventional- and
      balloon laryngoscopy-guided orolaryngeal intubation in the upper C-spine's
      osseous unit-orientation, segmental angulation, segmental SAC-sagittal surface
      areas (SSAs), segmental/total posterior SAC-aspect, and segmental SAC-width.
      Eight healthy volunteers were enrolled. A set of neutral head position (baseline)
      and two sets of intubation-lateral C-spine radiographs were obtained. Relative
      to baseline, both intubation techniques induced significant changes in the
      occiput (OCC)-, third cervical vertebra (C3)-, C4-, and C5-orientation, the OCC
      C1-segmental angulation, all the segmental SAC-SSAs, and the OCC-C1-, and C1-2
      posterior SAC-aspect (P < 0.05 to < 0.001); conventional intubation caused
      additional significant changes in C2-orientation, total (OCC through C5)
      posterior SAC-aspect, and OCC-C1-SAC-width (P < 0.05 to < 0.001). Relative to
      conventional intubation, balloon-assisted intubation caused less change in C3
      orientation and C2-3-SAC-width (P < 0.05), and less reduction in OCC-C1-, C1-2-,
      and C4-5-SAC-SSAs (P < 0.05 to < 0.01). Orotracheal intubation should be
      cautiously performed in patients with space-occupying upper-C-spine-SAC lesions,
      even if there is no concomitant osseous/ligamentous pathology. In such cases,
      balloon laryngoscopy may be chosen over the conventional technique, because it
      causes less SAC deformation. IMPLICATIONS: This study shows that direct
      laryngoscopy-guided orotracheal intubation causes deformation of the upper
      cervical space available for the cord, even in the absence of cervical spine
      instability. These effects are attenuated with balloon laryngoscopy, and thus,
      its use is recommended in patients with space-occupying lesions within the spinal
      canal.

PMID- 11323373
TI  - Preoxygenation with tidal volume and deep breathing techniques: the impact of
      duration of breathing and fresh gas flow.
AB  - Various techniques of "preoxygenation" before anesthetic induction have been
      advocated, including tidal volume breathing (TVB) for 3-5 min, four deep breaths
      (DB) in 0.5 min, and eight DB in 1 min. However, no study has compared the
      effectiveness of these techniques, assessed extending deep breathing beyond 1
      min, or investigated the influence of fresh gas flow (FGF) in the same subjects
      using a circle absorber system. In 24 healthy adult volunteers breathing oxygen
      from a circle absorber system by tight-fitting mask, we compared TVB/5 min and
      deep breathing at a rate of 4 DB/0.5 min for 2 min at 5, 7, and 10 L/min FGF.
      Inspired and end-tidal respiratory gases were measured at 0.5-min intervals.
      During TVB, end-tidal oxygen (ETO2) increased rapidly and plateaued by 2.5 min at
      86%, 88%, and 88% with 5, 7 and 10 L/min FGF, respectively. ETO2 values of > or
      =90% were attained between 3 and 4 min. Four DB/0.5 min increased ETO2 to 75%,
      77%, and 80% at 5, 7, and 10 L/min FGF. Eight DB/min resulted in ETO2 values of
      82% and 87% at 7 and 10 L/min, respectively. Extending deep breathing to 1.5 and
      2 min with 10 L/min FGF increased ETO2 by > or =90%, although a decrease in
      ETCo(2) was noted. We concluded that TVB/3-5 min was effective in achieving
      maximal "preoxygenation" whereas 4 DB/0.5 min resulted in submaximal
      "preoxygenation," and thus should be used only when time is limited. Increasing
      FGF from 5 to 10 L/min does not enhance "preoxygenation" with either TVB or 4
      DB/0.5 min. Deep breathing yields maximal "preoxygenation" when extended to 1.5
      or 2 min, and only when high (10 L/min) FGF is used. IMPLICATIONS: Using a circle
      absorber system, normal breathing of oxygen for 3-5 min achieves optimal
      oxygenation of the lungs; whereas 4 deep breaths in 30 s does not. However,
      extending deep breathing to 1.5-2 min and using a high flow of oxygen improves
      oxygenation of the lungs to the same degree as normal breathing for 3-5 min. This
      may have important implications for patient safety.

PMID- 11323374
TI  - The intubating laryngeal mask airway after induction of general anesthesia versus
      awake fiberoptic intubation in patients with difficult airways.
AB  - We performed the current study to compare tracheal intubation (TI) using awake
      fiberoptic intubation (AFOI) and TI using the intubating laryngeal mask airway
      (ILMA) in patients with difficult airway. Our hypothesis was that patients with
      difficult airways could be safely intubated after induction of anesthesia using
      the ILMA. After ethics approval and informed consent, 38 patients who were
      identified to have difficult airways were randomly assigned to AFOI or TI using
      the ILMA. Patients in the AFOI group had the usual sedation and airway
      topicalization. Patients in the ILMA group were induced with propofol for ILMA
      insertion and succinylcholine for TI. The first TI attempt was done blindly via
      the ILMA and all subsequent attempts were performed with fiberoptic guidance. All
      patients in the ILMA group were successfully ventilated. Successful TI was
      achieved in all patients in both groups. However, in 10% of the patients in the
      ILMA group, TI was achieved by a second anesthesiologist who was more experienced
      with the use of the ILMA. In a postoperative questionnaire, patients in the ILMA
      group were more satisfied with their method of TI (P < 0.01). The ILMA is a
      useful device in the management of patients with difficult airways and may be a
      valuable alternative to AFOI when AFOI is contraindicated or in the patient with
      the unanticipated difficult airway. IMPLICATIONS: The intubating laryngeal mask
      airway is a useful device in the management of patients with difficult airways
      and may be a valuable alternative to awake fiberoptic intubation (AFOI) when AFOI
      is contraindicated or in the patient with the unanticipated difficult airway.

PMID- 11323375
TI  - Arytenoid dislocation while using a McCoy laryngoscope.
AB  - Arytenoid dislocation (AD) involves either a complete disruption of the
      cricoarytenoid joint or a malpositioning of the arytenoid cartilages (AC) with
      reference to other laryngeal cartilages. In this report, we present a case of AD
      while using a McCoy laryngoscope. Although McCoy laryngoscope is recognized as a
      useful option for the cases of difficult endotracheal intubation, we are
      concerned that AD is likely with this device.

PMID- 11323376
TI  - Clarence J. Durshordwe, the International Anesthesia Research Society, and the
      World Federation of Societies of Anesthesiologists: the last true disciple of
      Francis Hoeffer McMechan.

PMID- 11323377
TI  - Remifentanil is a valuable alternative to contraindicated neuraxial analgesia in
      the parturients.

PMID- 11323379
TI  - A convenient way to secure intravenous, arterial, and other lines on extremities.

PMID- 11323378
TI  - Unlighted stylet tracheal intubation.

PMID- 11323380
TI  - Composition of CO(2) absorbents.

PMID- 11323381
TI  - End-tidal carbon dioxide tracing configuration depends on sampling size.

PMID- 11323382
TI  - Absence of reflex tachycardia after spinal anesthesia in the elderly.

PMID- 11323383
TI  - A preliminary investigation of remifentanil as a labor analgesic.

PMID- 11323384
TI  - The epileptogenic property of sevoflurane and in patients without epilepsy.

PMID- 11323385
TI  - New paradigms for cancer prevention.

PMID- 11323386
TI  - DNA-damaging carcinogen 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1)
      induces apoptosis via caspase-9 in primary cultured rat hepatocytes.
AB  - The mechanism of cytotoxicity induced by the DNA-damaging carcinogen 3-amino-1,4
      dimethyl-5H-pyrido[4,3-b] indole (Trp-P-1) was investigated in primary cultured
      rat hepatocytes. Cytotoxicity was caused by intact Trp-P-1 and not by
      metabolically activated derivatives prepared using a recombinant yeast strain
      AH22/pAMR2 expressing rat cytochrome P450 1A1, and not by metabolically activated
      derivatives. We also found internucleosomal DNA fragmentation 6 h after treatment
      with 30 microM Trp-P-1, indicating that the cytotoxicity was due to the induction
      of apoptosis. After treatment with Trp-P-1, c-Myc protein level increased in a
      time-dependent manner and p53 protein also increased transiently with a
      subsequent increase in Bax protein level. This apoptotic pathway required the
      activation of caspase-9 as an initiator after leakage of cytochrome c into the
      cytosol from mitochondria and the activation of caspase-3 and -7 as executioners,
      but not caspase-1, -6 or -8 as measured using the corresponding peptide
      inhibitors and substrates or western blotting. The activated caspases in turn
      cleaved poly(ADP-ribose) polymerase as an intracellular substrate. Furthermore,
      we detected NUC18-like endonuclease activity during apoptosis induced by Trp-P-1.
      These findings suggest that this apoptosis may have a role against heterocyclic
      amine-type carcinogens in normal cells.

PMID- 11323387
TI  - Fatty acid regulates gene expression and growth of human prostate cancer PC-3
      cells.
AB  - It has been proposed that the omega-6 fatty acids increase the rate of tumor
      growth. Here we test that hypothesis in the PC-3 human prostate tumor. We found
      that the essential fatty acids, linoleic acid (LA) and arachidonic acid (AA), and
      the AA metabolite PGE(2) stimulate tumor growth while oleic acid (OA) and the
      omega-3 fatty acid, eicosapentaenoic acid (EPA) inhibited growth. In examining
      the role of AA in growth response, we extended our studies to analyze changes in
      early gene expression induced by AA. We demonstrate that c-fos expression is
      increased within minutes of addition in a dose-dependent manner. Moreover, the
      immediate early gene cox-2 is also increased in the presence of AA in a dose
      dependent manner, while the constitutive cox-1 message was not increased. Three
      hours after exposure to AA, the synthesis of PGE(2) via COX-2 was also increased.
      Previous studies have demonstrated that AA was primarily delivered by low density
      lipoprotein (LDL) via its receptor (LDLr). Since it is known that hepatomas,
      acute myelogenous leukemia and colorectal tumors lack normal cholesterol
      feedback, we examined the role of the LDLr in growth regulation of the PC-3
      prostate cancer cells. Analysis of ldlr mRNA expression and LDLr function
      demonstrated that human PC-3 prostate cancer cells lack normal feedback
      regulation. While exogenous LDL caused a significant stimulation of cell growth
      and PGE(2) synthesis, no change was seen in regulation of the LDLr by LDL. Taken
      together, these data show that normal cholesterol feedback of ldlr message and
      protein is lost in prostate cancer. These data suggest that unregulated over
      expression of LDLr in tumor cells would permit increased availability of AA,
      which induces immediate early genes c-fos and cox-2 within minutes of uptake.

PMID- 11323388
TI  - Nitric oxide is involved in arsenite inhibition of pyrimidine dimer excision.
AB  - Arsenite is a human carcinogen reported to inhibit DNA repair. The binding of
      arsenite to functional thiol groups of DNA repair enzymes has in the past been
      suggested as a possible mechanism for the effect of arsenite on DNA repair.
      However, recent studies indicate that reactive oxygen species and nitric oxide
      are involved in arsenite toxicity. This research aims to elucidate the role of
      these possible mechanisms in the inhibition of UV-induced DNA repair by arsenite.
      As arsenite inhibits UV-DNA repair in Chinese hamster ovary cells, and this is a
      commonly used cell line for UV repair experiments, we used these cells to examine
      the effect of arsenite on the expression of UV-irradiated reporter genes. The T4
      UV endonuclease V-incorporated comet assay was used to examine specifically the
      effect of arsenite on pyrimidine dimer excision. We showed that inhibition of UV
      DNA repair by arsenite was suppressed by nitric oxide synthase inhibitors.
      Arsenite increased nitric oxide production and nitric oxide generators inhibited
      UV-DNA repair. The involvement of nitric oxide in the inhibition of pyrimidine
      dimer excision by arsenite was also confirmed in human fibroblasts. Investigation
      into the effect of oxidant modulators did not give a clear indication that
      reactive oxygen species are involved in arsenite inhibition of UV-DNA repair.
      Phenylarsine oxide, a strong thiol-reacting agent, did not inhibit pyrimidine
      dimer excision and also did not increase nitric oxide production. Our results
      show conclusively that nitric oxide is involved in the inhibition of pyrimidine
      dimer excision by arsenite. Reactive oxygen species and the binding of arsenite
      to functional thiol groups of DNA repair enzymes do not appear to be involved.

PMID- 11323389
TI  - No significant association between progesterone receptor exon 4 Val660Leu G/T
      polymorphism and risk of ovarian cancer.
AB  - Epidemiological studies suggest that ovarian cancer is an endocrine-related
      tumour, and progesterone exposure specifically may decrease the risk of ovarian
      cancer. To assess whether the progesterone receptor (PR) exon 4 valine to leucine
      amino acid variant is associated with specific tumour characteristics or with
      overall risk of ovarian cancer, we examined 551 cases of epithelial ovarian
      cancer and 298 unaffected controls for the underlying G-->T nucleotide
      substitution polymorphism. Stratification of the ovarian cancer cases according
      to tumour behaviour (low malignant potential or invasive), histology, grade or
      stage failed to reveal any heterogeneity with respect to the genotype defined by
      the PR exon 4 polymorphism. Furthermore, the genotype distribution did not differ
      significantly between ovarian cancer cases and unaffected controls. Compared with
      the GG genotype, the age-adjusted odds ratio (95% confidence interval) for risk
      of ovarian cancer was 0.78 (0.57-1.08) for the GT genotype, and 1.39 (0.47-4.14)
      for the TT genotype. In conclusion, the PR exon 4 codon 660 leucine variant
      encoded by the T allele does not appear to be associated with ovarian tumour
      behaviour, histology, stage or grade. This variant is also not associated with an
      increased risk of ovarian cancer, and is unlikely to be associated with a large
      decrease in ovarian cancer risk, although we cannot rule out a moderate inverse
      association between the GT genotype and ovarian cancer.

PMID- 11323390
TI  - Reduced DNA-dependent protein kinase activity is associated with lung cancer.
AB  - Reduced DNA repair capacity of carcinogen-induced DNA damage is now thought to
      significantly influence inherent susceptibility to lung cancer. DNA-dependent
      protein kinase (DNA-PK) is a serine-threonine kinase activated by the presence of
      double-strand breaks in DNA that appears to play a major role in non-homologous
      recombination and transcriptional control. The purpose of this study was to
      determine whether DNA-PK activity varies among individuals and how this affects
      lung cancer risk. DNA-PK activity in peripheral mononuclear cells from
      individuals with lung cancer (n = 41) was compared with lung cancer-free controls
      (n = 41). Interindividual variability was seen within each group, however,
      significant differences (P = 0.03) in DNA-PK activity between cases and controls
      were seen when comparing the distribution of enzyme activity among these two
      groups. The percentages of cases and controls with DNA-PK activity in the ranges
      2.5-5.0 and 7.6-10.0 units were 39 versus 20% and 7 versus 29%, respectively. The
      enzyme activity in peripheral mononuclear cells reflected that seen in bronchial
      epithelial cells, one progenitor cell for lung cancer, supporting the use of
      peripheral mononuclear cells for larger population-based studies of DNA-PK
      activity. Its role as a potential modifier for lung cancer risk was supported by
      the fact that cell growth in bronchial epithelial cells exposed to bleomycin was
      directly associated with enzyme activity. The results of this study demonstrate
      that reduced DNA-PK repair activity is associated with risk for lung cancer.

PMID- 11323391
TI  - p73 gene alterations and expression in primary oral and laryngeal squamous
      carcinomas.
AB  - p73, a recently identified gene, maps to chromosome region 1p36.3, which is
      frequently deleted in a variety of solid tumors. Although the gene shares
      sequence and functional homologies with p53, its suppressor function has not been
      proven. We investigated for the first time the genetic and expression status of
      the p73 gene and analyzed its flanking microsatellite loci on chromosome 1p36.3
      in 67 primary oral and laryngeal squamous cell carcinomas to determine their
      association with these tumors. Our results reveal two missense mutations at
      codons 469 and 477 and a silent mutation at codon 349 in the C-terminal domain.
      Site-directed mutagenesis of p73 cDNA with these mutations and a p21
      transactivation assay failed to show any significant functional consequences of
      these mutations. Microsatellite analysis of the flanking loci of p73 in region
      1p36 showed overall alterations (loss of heterozygosity and instability)
      frequency of 39%, 16% at the proximal marker and 46% at the distal markers. Of
      the 21 cases for which we did protein expression analyses, 11 tumors had a >2
      fold variation compared with matching histologically normal mucosa. Our study
      shows that: (i) intragenic alterations in this gene are rare and lack functional
      significance; (ii) its variable expression argues against a tumor suppressor
      function; (iii) this gene plays a minor role in head and neck squamous carcinoma;
      (iv) a distal site to this gene on 1p36 may harbor another suppressor gene.

PMID- 11323392
TI  - Chronic Trypanosoma cruzi infection associated with low incidence of 1,2
      dimethylhydrazine-induced colon cancer in rats.
AB  - Experimental data have demonstrated that chronic infection with intracellular
      parasites may enhance resistance against some types of tumour. This phenomenon
      has not yet been demonstrated for experimental Trypanosoma cruzi chronic
      infection. This study investigated the effect of a specific colon cancer inducing
      drug, 1,2-dimethylhydrazine (DMH), on chronically T.cruzi infected Wistar rats.
      Infection was obtained by inoculation of 10(5) tripomastigote forms by
      subcutaneous (s.c.) route. Acute phase of the infection was monitored every other
      day by examination of a blood smear from each animal until negativation. In the
      early chronic phase of the infection, colon adenocarcinoma was induced by weekly
      s.c. injections of DMH at a dose of 20 mg/kg body weight for 12 weeks. 102
      animals were divided in four test groups: 39 infected rats received DMH (group
      1); 32 non-infected rats received DMH (group 2); 16 infected rats and 15 non
      infected animals were used as control groups. Animals were killed 6 months after
      the first dose of DMH. The whole colon was removed and prepared for light
      microscopic examination. Twelve animals from group 1 and 22 from group 2 had
      colon adenocarcinomas, the proportion of cancer being 30.7 and 68.7%,
      respectively (chi(2) = 10.16; P < 0.05). The relative risk of having a colon
      tumor in infected animals (group 1) was 0.45 (IC 95% 0.26-0.76), which is a
      protective risk compared with non-infected animals. These findings show that
      chronic infection with T.cruzi is associated with a lower incidence of DMH
      induced colon cancer in rats.

PMID- 11323393
TI  - The rapid alveolar absorption of diesel soot-adsorbed benzo[a]pyrene:
      bioavailability, metabolism and dosimetry of an inhaled particle-borne
      carcinogen.
AB  - Exposure to diesel exhaust may contribute to lung cancer in humans. It remains
      unclear whether the carbonaceous core of the soot particle or its coat of
      adsorbed/condensed organics contributes most to cancer risk. Equally unclear are
      the extent and rate at which organic procarcinogens desorb from soot particles in
      the lungs following inhalation exposure and the extent of their metabolic
      activation in the lungs. To explore the basic relationship between a model
      polycyclic aromatic hydrocarbon (PAH) and a typical carrier particle, we
      investigated the rate and extent of release and metabolic fate of benzo[a]pyrene
      (BaP) adsorbed on the carbonaceous core of diesel soot. The native organic
      content of the soot had been denuded by toluene extraction. Exogenous BaP was
      adsorbed onto the denuded soot as a surface coating corresponding to 25% of a
      monomolecular layer. Dogs were exposed by inhalation to an aerosol bolus of the
      soot-adsorbed BAP: Following deposition in the alveolar region a fraction of BaP
      was rapidly desorbed from the soot and quickly absorbed into the circulation.
      Release rates then decreased drastically. When coatings reached approximately 16%
      of a monolayer the remaining BaP was not bioavailable and was retained on the
      particles after 5.6 months in the lung. However, the bioavailability of particles
      transported to the lymph nodes was markedly higher; after 5.6 months the surface
      coating of BaP was reduced to 10%. BaP that remained adsorbed on the soot surface
      after this period was approximately 30% parent compound. In contrast, the rapidly
      released pulse of BaP, which was quickly absorbed through the alveolar epithelium
      after inhalation, appeared mostly unmetabolized in the circulation, along with
      low concentrations of phase I and phase II BaP metabolites. However, within
      approximately 1 h this rapidly absorbed fraction of BaP was systemically
      metabolized into mostly conjugated phase II metabolites. The results indicate
      that absorption through the alveolar epithelium is an important route of entry to
      the circulation of unmetabolized PAHS:

PMID- 11323394
TI  - Telomerase activation and p53 mutations in urethane-induced A/J mouse lung tumor
      development.
AB  - The mouse telomerase holoenzyme, which synthesizes telomeric DNA de novo, is a
      ribonucleoprotein complex that includes the mouse telomerase RNA component
      (mTERC), mouse telomerase-associated protein (mTEP1) and mouse telomerase reverse
      transcriptase (mTERT). To determine the role of telomerase in urethane-induced
      lung tumorigenesis in A/J mice we examined telomerase activity and the expression
      of each telomerase subunit in 20 tumor samples, harvested at 16, 28, 40 and 50
      weeks after urethane treatment. The telomeric repeat amplification protocol assay
      showed that statistically significant telomerase activation occurred both early
      and late in tumorigenesis. Semi-quantitative reverse transcription-polymerase
      chain reaction analysis revealed that mRNA expression levels of mTEP1 and mTERT
      were up-regulated during tumor progression, while mTERC expression was not
      significantly different between tumors and normal lung. We further examined mTEP1
      protein expression in normal lung tissue and lung tumors; western blot analysis
      showed preferential expression of mTEP1 protein in lung tumors compared with
      normal lung and immunohistochemistry revealed that a majority of the adenoma
      cells were positively stained in the nucleus, whereas only a few of the adjacent
      normal alveolar cells were immunoreactive. In addition, we investigated DNAs of
      the 20 tumor samples by single strand conformation polymorphism and sequencing
      analyses to examine whether alterations of the p53 gene in exons 5-8 were
      associated with telomerase activity. Although we found one nonsense, two
      missense, two silent and one simultaneous double mutation at different codons in
      six late stage tumors, there was no apparent correlation between telomerase
      activity and p53 mutations. Collectively, these results suggest that mTEP1 as
      well as mTERT may be involved in the regulation of telomerase activity and that
      telomerase activation may contribute to lung tumorigenesis in A/J mice
      independently of p53 gene alterations.

PMID- 11323395
TI  - Mechanisms of Cr(VI)-induced p53 activation: the role of phosphorylation, mdm2
      and ERK.
AB  - The present study investigated the molecular mechanisms of p53 activation induced
      by Cr(VI), using human lung epithelial A549 cells. Cr(VI) increased both protein
      level and transactivation ability of p53 protein. The activation of p53 is at the
      protein level instead of the transcriptional level. The degradation of p53 was
      dramatically decreased upon stimulation by Cr(VI). In addition, Cr(VI) treatment
      decreased the interaction of p53 with mdm2 protooncoprotein, which blocks the
      transactivation ability of p53 and promotes the degradation of p53 protein. In
      response to Cr(VI) treatment, p53 protein became phosphorylated and acetylated at
      Ser15 and Lys382, respectively. The phosphorylation levels at either Ser20 or
      Ser392 did not show any significant alterations. Since previous studies report
      that it is Ser20 and not Ser15 phosphorylation that contributes to mdm2
      dissociation from p53, the results obtained from the current investigation
      suggest a different mechanism: Ser15 instead of Ser20 may play a key role in the
      dissociation of mdm2 in response to Cr(VI). Erk, a member of mitogen-activated
      protein kinase, acts as the upstream kinase for the phosphorylation of the p53
      Ser15 site.

PMID- 11323396
TI  - Steroid hormones modulate expression of cytochrome P450 enzymes in male hamster
      reproductive tract and leiomyosarcomas.
AB  - Syrian hamsters treated with estrogen and androgen for 8 months develop
      leiomyosarcomas in the vas deferens. Metabolism of estrogen by cytochrome P450s
      (CYPs) produces catechols and reactive oxygen species, and may contribute to
      tumor formation. To examine this issue, male hamsters were treated with 17 beta
      estradiol (E2), testosterone propionate (TP) or both hormones. Reproductive tract
      tissues from control and treated animals were immunostained with antibodies
      specific for four CYP enzymes (1A1, 1A2, 1B1 and 3A1/2). Immunoreactive CYP1A1
      was not found in the reproductive tract of control or treated animals. In
      untreated hamsters, CYP1A2 was detected only in principal cells of the caput
      epididymis. TP alone had no effect, but treatment with E2 induced expression of
      CYP1A2 in columnar epithelial cells throughout the epididymis and lining of the
      vas deferens. Treatment with E2 + TP blocked the induction of CYP1A2 seen in
      surface epithelial cells treated with E2 alone, but not the constitutive
      expression of this enzyme. Instead, simultaneous exposure to both hormones
      induced CYP1A2 in basal cells of the epididymis and vas deferens. CYP3A1/2 was
      not detected in the reproductive tract of control or TP-treated males, but
      immunostaining was induced in the inner layer of vas deferens smooth muscle by
      E2, and in all smooth muscle layers by dual hormone treatment. In controls,
      CYP1B1 was present in smooth muscle lining the epididymis and surrounding the vas
      deferens and dual hormone treatment increased staining intensity for CYP1B1 in
      these cells. Immunoreactive CYP1A2 was not detectable in leiomyosarcomas but the
      enzyme was present in both columnar and basal cells of the vas deferens
      epithelium adjacent to the tumors. In contrast, tumor cells showed heterogeneous
      expression of both CYP1B1 and CYP3A1/2. The relationships between hormone
      treatment, differential CYP expression and tumor formation strengthen our
      hypothesis that metabolism of estrogen is an important element in this model of
      hormonal carcinogenesis.

PMID- 11323397
TI  - Photodynamic DNA damage mediated by delta-aminolevulinic acid-induced porphyrins.
AB  - The mutagenic properties of UVA are thought to be predominantly radical-mediated,
      which supposes endogenous sensitizers. In order to investigate a possible role of
      porphyrins, their synthesis was induced in a murine leukemia P388D1 cell model by
      treatment with delta-aminolevulinic acid (delta-ala). Intra-cellular
      protoporphyrin IX reached a plateau after about 2 h, whereas soluble porphyrins,
      probably the photostable uro- and/or coproporphyrins, were excreted. Irradiation
      of treated cells by UVA (tanning lamp) but also by visible light was found to
      generate in DNA a significant increase of 8-oxo-7,8-dihydro-2'-deoxyguanosine, a
      mutagenic marker of oxidative damage. The different parameters involved in this
      photodynamic effect are reported, namely delta-ala concentration and loading
      time, light dosage and the influence of intracellular and medium-excreted
      porphyrins. These results point to an implication of porphyrins in solar-induced
      carcinogenicity but also in possible adverse effects of the medical applications
      of photodynamic therapy and diagnosis.

PMID- 11323398
TI  - The role of the C' terminus of murine p53 in the p53/mdm-2 regulatory loop.
AB  - Mdm-2 plays a central role in the regulation of p53 protein level and activity.
      Although the interaction of mdm-2 and p53 occurs through the N-terminus of the
      p53 protein, our present data suggest that the C' terminus plays an important
      role in the regulation of the p53/mdm-2 loop. Comparative analysis of the murine
      regularly spliced form of p53 (RSp53) and a physiological C-terminally modified
      p53 protein, which results from alternative splicing of the p53 mRNA (ASp53),
      indicated that the two isoforms behave differently in the p53/mdm-2 loop. We
      found that ASp53 can preferentially induce higher levels of the mdm-2 protein,
      compared with RSp53. Although the transactivation capacity of both forms is
      inhibited by mdm-2, only RSp53 is directed to proteolytic degradation by mdm-2,
      while ASp53 is relatively resistant. We present evidence that suggests that ASp53
      protein levels determine the biological activities mediated by RSp53, such as the
      induction of apoptosis, through the mdm-2/p53 regulatory loop. We suggest,
      therefore, a new mechanism for the regulation of p53, and show that alteration of
      the p53 extreme C' terminus can significantly change the transcription activity
      and the resistance to degradation properties of the p53 protein.

PMID- 11323399
TI  - Effects of occupation, lifestyle and genetic polymorphisms of CYP1A1, CYP2E1,
      GSTM1 and GSTT1 on urinary 1-hydroxypyrene and 2-naphthol concentrations.
AB  - This study was undertaken to determine the effects of occupation, lifestyle and
      the genetic polymorphisms of cytochrome P450 1A1 (CYP1A1), cytochrome P450 2E1
      (CYP2E1) and glutathione S-transferases micro1 (GSTM1) and 1 (GSTT1) on the
      concentrations of urinary 1-hydroxypyrene (1-OHP) and 2-naphthol among Korean
      coke oven workers and university students. The study subjects included 90 coke
      oven workers and 128 university students. A questionnaire was used to obtain
      detailed data about the work area, smoking habits and food intake of subjects.
      Associations between urinary polycyclic aromatic hydrocarbon (PAH) concentrations
      and occupation, smoking status, total airborne PAH level and genetic
      polymorphisms were tested. Urinary 1-OHP and 2-naphthol concentrations were
      higher in coke oven workers than in students and correlated significantly with
      work area. Urinary 2-naphthol concentrations increased with an increase in the
      level of cigarette smoking in students. Total airborne PAH level correlated with
      urinary 1-OHP concentration in coke oven workers. Urinary 1-OHP and 2-naphthol
      concentrations were higher in coke oven workers with the c1/c2 or c2/c2 genotype
      of CYP2E1 than in those with the c1/c1 genotype. Urinary 2-naphthol
      concentrations were higher in GSTM1-null workers than in GSTM1-positive workers.
      In multiple regression analysis CYP2E1 was a significant factor determining
      urinary 1-OHP concentrations in coke oven workers. CYP2E1 and GSTM1 were
      significant determinants for urinary 2-naphthol concentrations in coke oven
      workers and GSTM1 and smoking were prognosticators among university students.
      Urinary 1-OHP is a better indicator of occupational exposure to PAH in coke oven
      workers than 2-naphthol, whereas urinary 2-naphthol may be more sensitive for non
      occupational inhalation exposure to PAH. In occupationally exposed populations
      CYP2E1 and GSTM1 appear to play an important role in the metabolism of pyrene and
      naphthalene. In individuals not occupationally exposed to PAHs GSTM1 and smoking
      seem to influence the urinary concentration of 2-naphthol.

PMID- 11323400
TI  - Changes in essential fatty acid patterns associated with normal liver
      regeneration and the progression of hepatocyte nodules in rat
      hepatocarcinogenesis.
AB  - Changes in lipid metabolism were monitored in rat hepatocyte nodules at certain
      time points over 9 months. Tissue obtained from partially hepatectomized rats,
      collected over a period of 7 days, were included as a control for normal
      hepatocyte cell proliferation. Two important features regarding the lipid
      profiles of hepatocyte nodules and normal regenerating liver were the increased
      concentrations of phosphatidylethanolamine (PE), resulting in a decreased
      phosphatidylcholine/phosphatidylethanolamine (PC/PE) ratio, and cholesterol.
      These changes coincided with increased membrane fluidity in the nodules and
      regenerating liver. With respect to the fatty acid (FA) profiles of the nodules,
      C18:1omega9 and C18:2omega6 increased in PE and PC whereas C20:4omega6 decreased
      in PC and increased in PE. C22:5omega6 and C22:6omega3, the end products of the
      omega6 and omega3 metabolic pathways, respectively, decreased in PC and remained
      unchanged in PE. The FA levels in PC reflected an impaired delta-6 desaturase
      enzyme, whereas this effect was masked in PE due to the increased concentration
      of this phospholipid fraction. In regenerating liver, the FA profiles of PC and
      PE showed the same pattern as described for the hepatocyte nodules, except for
      C18:1omega9 which decreased in PC and increased non-significantly in PE. The
      increased C18:1omega9 level, a FA with anti-oxidative properties, as well as the
      decreased levels of the long-chain polyunsaturated fatty acids (C20 and C22
      carbon chains), have been associated with the decreased lipid peroxidation level
      in hepatocyte nodules. The resultant decrease in peroxidative metabolites, known
      to affect apoptosis, could be important in the progression of the nodules into
      neoplasia. The present results indicate that the altered lipid parameters
      associated with hepatocyte nodules closely mimics cellular proliferation in
      regenerating liver and could be responsible for the enhanced proliferation and/or
      altered growth pattern in these lesions. The altered FA profiles suggest various
      pathways in which FA could play a role in transmembrane signalling related to the
      altered cell proliferative and apoptotic pathways. The persistent changes in the
      hepatocyte nodules suggest that the lipid metabolism escapes the regulatory
      mechanisms required for normal cellular homeostasis at different levels.

PMID- 11323401
TI  - Mrp2-deficiency in the rat impairs biliary and intestinal excretion and
      influences metabolism and disposition of the food-derived carcinogen 2-amino-1
      methyl-6-phenylimidazo.
AB  - While metabolism of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), the
      most abundant food-derived heterocyclic amine and carcinogen, has been studied
      extensively in several species, transport of this compound and its metabolites
      has not been defined yet. Therefore we studied metabolism and disposition of PhIP
      in Wistar and Mrp2-deficient TR(-) rats to determine the role of Mrp2 in the
      defence against this compound. In the first 2 h after intravenous dosing, total
      excretion of PhIP and its metabolites in bile was > 4-fold reduced in TR(-) rats
      compared with Wistar rats, while excretion in the urine of the TR(-) rat was 1.8
      fold higher. This difference was the result of an almost complete absence of
      secretion of glucuronidated metabolites but also a reduced level of secretion of
      unchanged PhIP into bile of the TR(-) rat. Direct intestinal excretion of
      unmetabolized PhIP was 3-fold higher in Wistar versus TR(-) rats. As a
      consequence, PhIP tissue levels in the liver were 1.7-fold higher in TR(-) rats,
      and tissue binding of PhIP, determined after ethanol extraction, was elevated by
      a similar magnitude. Mrp2-mediated transport of the parent compound PhIP is
      glutathione (GSH)-dependent, because GSH depletion by L-buthionine-[S,R]
      sulfoximine (BSO) treatment in Wistar rats reduced intestinal secretion to the
      same level as that in TR(-) rats. TR(-) rats produced less glucuronides and 4'-OH
      PhIP in the 2 h following PhIP administration. We conclude that Mrp2 protects
      against the carcinogen PhIP by biliary excretion of the parent compound and all
      major phase-II metabolites, but, more importantly, also by direct extrusion of
      the parent compound from the gut mucosa.

PMID- 11323402
TI  - Mitotic checkpoint genes hBUB1, hBUB1B, hBUB3 and TTK in human bladder cancer,
      screening for mutations and loss of heterozygosity.
AB  - Chromosomal instability is common in bladder cancer and could be caused by
      mutations of mitotic checkpoint genes. Therefore we screened for mutations of the
      mitotic checkpoint genes hBUB1, hBUB1B, hBUB3 and TTK in six aneuploid bladder
      cancer cell lines and 15 human bladder tumours. The screening was performed by
      sequence analysis of the entire coding regions of the four genes. No mutations
      were detected in any of the four genes. We detected several sequence variations
      in hBUB1, hBUB1B and TTK both new and previously published. The genetic stability
      of the four gene loci were tested by loss of heterozygosity (LOH) analysis in the
      15 patient samples, showing one LOH for each of the hBUB1B, hBUB3 and TTK loci
      (6.7%) of the cases, all in different tumour samples. No LOH was detected at
      hBUB1. We conclude that both mutational inactivation, and loss of one allele, of
      the examined mitotic checkpoint genes are relatively uncommon.

PMID- 11323403
TI  - The multiplicative model for cancer risk assessment: applicability to acrylamide.
AB  - According to a multiplicative model for prediction of cancer risk for genotoxic
      agents the incremental cancer risk is, for low-intermediate exposures,
      proportional to target doses of the genotoxic substance and to the background
      risk in control groups. This model has been applied to evaluate cancer tests of
      acrylamide in rodents. Because of its reactivity toward DNA, glycidamide is
      assumed to be the causative genotoxic metabolite of acrylamide. Evaluation of
      experimental data according to the multiplicative model shows that mice, compared
      with rats, are of the order of 10 times more sensitive per administered dose of
      acrylamide. The US EPA procedure would, however, generally predict rats to be
      about twice as sensitive as mice to carcinogenic chemicals, because their
      estimates are based on scaling of the dose per square meter body surface area, as
      a surrogate for metabolic differences between the species. The comparison of rats
      and mice with respect to observed cancer incidence is at a key position in the
      evaluation of the usefulness of risk models for extrapolation between species. In
      the present study mice and rats were compared, with respect to in vivo doses of
      acrylamide and the metabolite glycidamide, after exposure to acrylamide. The
      relative in vivo doses were inferred from levels of hemoglobin adducts. The
      adduct levels from glycidamide were, per administered dose of acrylamide,
      approximately 3-10 times higher in mice than in rats. In combination with the
      above mentioned higher sensitivity of mice than rats in cancer tests of
      acrylamide this is compatible with the concept that glycidamide is the key
      genotoxic factor in acrylamide exposure. Furthermore, it is shown that the
      multiplicative, i.e. relative, risk model and measurements of the dose of the
      genotoxic factor give good prediction of the observed risk from acrylamide in
      cancer tests with rats and mice.

PMID- 11323404
TI  - Curcumin modifies Apc(min) apoptosis resistance and inhibits 2-amino 1-methyl-6
      phenylimidazo[4,5-b]pyridine (PhIP) induced tumour formation in Apc(min) mice.
AB  - Curcumin, the active ingredient of the rhizome of Curcuma longa, promotes
      apoptosis and may have chemopreventive properties. This study investigates the
      effects of curcumin on apoptosis and tumorigenesis in male Apc(min) mice treated
      with the human dietary carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5
      b]pyridine (PhIP). Intestinal epithelial apoptotic index in response to PhIP
      treatment was approximately twice as great in the wild-type C57BL/6 APC(+/+)
      strain than in Apc(min) mice (3.7% Apc(+/+) versus 1.9% Apc(min); P < 0.001).
      PhIP promoted tumour formation in Apc(min) proximal small intestine (4.6 tumours
      per mouse, PhIP treated versus 2.1 tumours per mouse, control untreated; P <
      0.05). Curcumin enhanced PhIP-induced apoptosis (4.0% curcumin + PhIP versus 2.1%
      PhIP alone; P < 0.01) and inhibited PhIP-induced tumorigenesis in the proximal
      small intestine of Apc(min) mice (2.2 tumours per mouse, curcumin + PhIP versus
      4.6 tumours per mouse PhIP alone; P < 0.05). This study shows that the Apc(min)
      genotype is associated with resistance to PhIP-induced apoptosis in intestinal
      epithelium. Curcumin attenuates Apc(min) resistance to PhIP-induced apoptosis and
      inhibits PhIP-induced tumorigenesis in proximal Apc(min) mouse small intestine.

PMID- 11323405
TI  - Association between manganese superoxide dismutase (MnSOD) gene polymorphism and
      breast cancer risk.
AB  - Superoxide dismutases play a key role in the detoxification of superoxide
      radicals and thus protect cells from damage induced by free radicals. Within
      mitochondria manganese superoxide dismutase (MnSOD) provides a major defence
      against oxidative damage by reactive oxygen species. Polymorphism in the
      mitochondrial targeting sequence of MnSOD has recently been associated with risk
      of breast cancer. We examined this in a study population consisting of 483 breast
      cancer cases and 482 controls, all of Finnish Caucasian origin. Odds ratios (OR)
      and 95% confidence intervals (95% CIs) were estimated by unconditional logistic
      regression. MnSOD genotypes containing the variant A allele were found to be
      associated with a 1.5-fold (95% CI 1.1-2.0) increased risk of breast cancer
      compared with those with the homozygous wild-type genotype (MnSOD VV). This
      finding supports the proposal that MnSOD genotypes may modify individual breast
      cancer risk.

PMID- 11323407
TI  - A human mitochondrial ferritin encoded by an intronless gene.
AB  - Ferritin is a ubiquitous protein that plays a critical role in regulating
      intracellular iron homoeostasis by storing iron inside its multimeric shell. It
      also plays an important role in detoxifying potentially harmful free ferrous iron
      to the less soluble ferric iron by virtue of the ferroxidase activity of the H
      subunit. Although excess iron is stored primarily in cytoplasm, most of the
      metabolically active iron in cells is processed in mitochondria. Little is yet
      known of how these organelles regulate iron homeostasis and toxicity. Here we
      report an unusual intronless gene on chromosome 5q23.1 that encodes a 242-amino
      acid precursor of a ferritin H-like protein. This 30-kDa protein is targeted to
      mitochondria and processed to a 22-kDa subunit that assembles into typical
      ferritin shells and has ferroxidase activity. Immunohistochemical analysis showed
      that it accumulates in high amounts in iron-loaded mitochondria of erythroblasts
      of subjects with impaired heme synthesis. This new ferritin may play an important
      role in the regulation of mitochondrial iron homeostasis and heme synthesis.

PMID- 11323408
TI  - Bombesin and substance P analogues differentially regulate G-protein coupling to
      the bombesin receptor. Direct evidence for biased agonism.
AB  - Substance P analogues including [d-Arg1,d-Phe5,d-Trp7,9,Leu11]substance P (SpD)
      act as "broad spectrum neuropeptide antagonists" and are potential anticancer
      agents that inhibit the growth of small cell lung cancer cells in vitro and in
      vivo. However, their mechanism of action is controversial and not fully
      understood. Although these compounds block bombesin-induced mitogenesis and
      signal transduction, they also have agonist activity. The mechanism underlying
      this agonist activity was examined. SpD binds to the ligand-binding site of the
      bombesin/gastrin-releasing peptide receptor and blocks the bombesin-stimulated
      increase in [Ca2+]i within the same concentration range that causes sustained
      activation of c-Jun N-terminal kinase and extracellular signal-regulated protein
      kinase (ERK). The activation of c-Jun N-terminal kinase by SpD and bombesin is
      blocked by dominant negative inhibition of G(alpha12). The ERK activation by SpD
      is pertussis toxin-sensitive in contrast to ERK activation by bombesin, which is
      pertussis toxin-insensitive but dependent on epidermal growth factor receptor
      phosphorylation. SpD does not simply act as a partial agonist but differentially
      modulates the activation of the G-proteins G(alpha12), G(i), and G(q) compared
      with bombesin. This unique ability allows the bombesin receptor to couple to G(i)
      and at the same time block receptor activation of G(q). Our results provide
      direct evidence that SpD is acting as a "biased agonist" and that this has
      physiological relevance in small cell lung cancer cells. This validation of the
      concept of biased agonism has important implications in the development of novel
      pharmacological agents to dissect receptor-mediated signal transduction and of
      highly selective drugs to treat human disease.

PMID- 11323409
TI  - The v-Crk oncogene enhances cell survival and induces activation of protein
      kinase B/Akt.
AB  - The v-Crk oncogene encodes an adaptor protein containing an SH2 domain and an SH3
      domain. v-Crk-transformed fibroblast cells display enhanced tyrosine
      phosphorylation levels, and the v-Crk protein localizes in focal adhesions,
      suggesting that transformation may be due to enhanced focal complex signaling.
      Here we investigated the mechanism of transformation and found that v-Crk
      transformed NIH 3T3 cells display growth rates and serum requirements similar to
      control cells. However, v-Crk enhanced survival in conditions of serum
      starvation. Both an intact SH2 and SH3 domain are required; moreover, SH2 mutants
      displayed dominant interfering properties, enhancing cell death. Using other cell
      death-inducing stimuli, it appeared that v-Crk in general inhibits apoptosis and
      enhances cell survival. In search of the signaling pathways involved, we found
      that v-Crk-transformed cells show constitutively higher levels of phospho-protein
      kinase B (PKB)/Akt and PKB/Akt activity, especially in conditions of serum
      starvation. These data strongly suggest involvement of the phosphatidylinositol 3
      kinase/PKB survival pathway in the v-Crk-induced protection against apoptosis. In
      accordance, inhibition of this pathway by wortmannin or LY924002 reduced
      protection against starvation-induced apoptosis. In addition to the
      phosphatidylinositol 3-kinase/PKB pathway, a MEK-dependent pathway and an unknown
      additional pathway are also implicated in resistance against apoptosis.
      Activation of survival pathways may be the most important function of v-Crk in
      its oncogenic properties.

PMID- 11323410
TI  - Post-translational processing of bovine chondromodulin-I.
AB  - Chondromodulin-I (ChM-I) is a small glycoprotein that is abundant in fetal
      cartilage. Mature chondromodulin-I is processed from a larger precursor form,
      presumably at a proteolytic site RERR-ELVR. The precursor, mature chondromodulin
      I and two processed products, the remnant left after removal of mature
      chondromodulin-I and a smaller, unglycosylated form, were identified using
      antipeptide antisera. The products of chondromodulin-I precursor processing were
      seen in cultured chondrocytes, a stable long-term culture chondrosarcoma cell
      line, as well as Chinese hamster ovary (CHO) cells transfected with an expression
      plasmid that contained cDNA coding for the chondromodulin-I precursor. Pulse
      chase analysis allowed a processing pathway to be analyzed for chondromodulin-I.
      To further dissect the processing events, three constructs that express
      recombinant wild-type or mutant chondromodulin-I were transfected into CHO cells.
      We showed that chondromodulin-I is cleaved intracellularly at the predicted
      cleavage site, and that the mature glycopeptide is rapidly secreted immediately
      after processing. The chondromodulin-1 precursor has a short half-life and is not
      readily apparent in tissue samples, suggesting that chondromodulin is not a
      member of the juxtacrine family of growth factors, despite some similarities. The
      smaller unglycosylated form of chondromodulin-I was only observed in cartilage
      and not in short-term cultures or transfected cells, suggesting an extracellular
      processing event. No processing occurred when the precursor cleavage site was
      mutated to RERQ-SLVR or when precursor chondromodulin-I was expressed in the
      furin-deficient CHO cell line, suggesting the involvement of furin in processing.

PMID- 11323411
TI  - Phosphotyrosines 627 and 659 of Gab1 constitute a bisphosphoryl tyrosine-based
      activation motif (BTAM) conferring binding and activation of SHP2.
AB  - A major Grb2-associated binder-1 (Gab1) binding partner in epidermal growth
      factor (EGF)-stimulated cells is protein-tyrosine phosphatase (PTPase) SHP2,
      which contains tandem SH2 domains. The SHP2 PTPase activity is required for
      activation of the extracellular signal-regulated kinase (ERK) subfamily of
      mitogen-activated protein (MAP) kinase by EGF. To investigate the mechanism by
      which Gab1 and SHP2 mediate ERK activation, we characterized the Gab1-SHP2
      interaction. We found that both Tyr-627 and Tyr-659 of Gab1 were required for
      SHP2 binding to Gab1 and for ERK2 activation by EGF. Far Western blot analysis
      suggested that the tandem SH2 domains of SHP2 bind to Gab1 in a specific
      orientation, in which the N-SH2 domain binds to phosphotyrosine (Tyr(P))-627 and
      the C-SH2 domain binds to Tyr(P)-659. When assayed with peptide substrates, SHP2
      PTPase was activated by a bisphosphopeptide containing both Tyr(P)-627 and Tyr(P)
      659, but not by monophosphopeptides containing Tyr(P)-627 or Tyr(P)-659 or a
      mixture of these monophosphopeptides. These results suggest that Tyr(P)-627 and
      Tyr(P)-659 of Gab1 constitute a bisphosphoryl tyrosine-based activation motif
      (BTAM) that binds and activates SHP2. Remarkably, while a constitutively active
      SHP2 (SHP2DeltaN) could not rescue the defect of a SHP2-binding defective Gab1
      (Gab1FF) in ERK2 activation, expression of a Gab1FF-SHP2DeltaN chimera resulted
      in constitutive activation of ERK2 in transfected cells. Thus, physical
      association of activated SHP2 with Gab1 is necessary and sufficient to mediate
      the ERK mitogen-activated protein kinase activation. Phosphopeptides derived from
      Gab1 were dephosphorylated by active SHP2 in vitro. Consistently, substrate
      trapping experiments with a SHP2 catalytic inactive mutant suggested that Gab1
      was a SHP2 PTPase substrate in the cells. Therefore, Gab1 not only is a SHP2
      activator but also is a target of its PTPase.

PMID- 11323412
TI  - Loss of E-cadherin expression in melanoma cells involves up-regulation of the
      transcriptional repressor Snail.
AB  - Malignant transformation of melanocytes frequently coincides with loss of E
      cadherin expression. Here we show that loss of E-cadherin in melanoma cell lines
      does not involve mutations in the E-cadherin gene, promoter methylation, or
      alterations in expression of AP-2 transcription factors as suggested previously.
      In a panel of different melanoma cell lines, E-cadherin expression was negatively
      regulated by up-regulation of the transcription factor Snail. In comparison with
      primary human melanocytes, where Snail expression was not detected by reverse
      transcription-polymerase chain reaction, significant expression was found in all
      eight melanoma cell lines. In parallel, Western blot and reverse transcription
      polymerase chain reaction analysis revealed strong reduction of E-cadherin
      expression in the melanoma cells. Consistently, transient transfection of a Snail
      expression plasmid into human primary melanocytes led to significant down
      regulation of E-cadherin, whereas transient and stable transfection of an
      antisense Snail construct induced reexpression of E-cadherin in Mel Ju and Mel Im
      melanomas. In summary, we conclude that activation of Snail expression plays an
      important role in down-regulation of E-cadherin and tumorigenesis of malignant
      melanomas.

PMID- 11323413
TI  - Characterization of the mammalian initiation factor eIF2B complex as a GDP
      dissociation stimulator protein.
AB  - Initiation factor eIF2B mediates a key regulatory step in the initiation of mRNA
      translation, i.e. the regeneration of active eIF2.GTP complexes. It is composed
      of five subunits, alpha-epsilon. The largest of these (epsilon) displays
      catalytic activity in the absence of the others. The catalytic mechanism of eIF2B
      and the functions of the other subunits remain to be clarified. Here we show
      that, when present at similar concentrations to eIF2, mammalian eIF2B can mediate
      release of eIF2-bound GDP even in the absence of free nucleotide, indicating that
      it acts as a GDP dissociation stimulator protein. Consistent with this, addition
      of GDP to purified eIF2.eIF2B complexes causes them to dissociate. The
      alternative sequential mechanism would require that eIF2Bepsilon itself bind GTP.
      However, we show that it is the beta-subunit of eIF2B that interacts with GTP.
      This indicates that binding of GTP to eIF2B is not an essential element of its
      mechanism. eIF2B preparations that lack the alpha-subunit display reduced
      activity compared with the holocomplex. Supplementation of such preparations with
      recombinant eIF2Balpha markedly enhances activity, indicating that eIF2Balpha is
      required for full activity of mammalian eIF2B.

PMID- 11323414
TI  - Functional roles for the cytoplasmic domain of the type III transforming growth
      factor beta receptor in regulating transforming growth factor beta signaling.
AB  - Transforming growth factor beta (TGF-beta) signals through three high affinity
      cell surface receptors, TGF-beta type I, type II, and type III receptors. The
      type III receptor, also known as betaglycan, binds to the type II receptor and is
      thought to act solely by "presenting" the TGF-beta ligand to the type II
      receptor. The short cytoplasmic domain of the type III receptor is thought to
      have no role in TGF-beta signaling because deletion of this domain has no effect
      on association with the type II receptor, or with the presentation role of the
      type III receptor. Here we demonstrate that the cytoplasmic domains of the type
      III and type II receptors interact specifically in a manner dependent on the
      kinase activity of the type II receptor and the ability of the type II receptor
      to autophosphorylate. This interaction results in the phosphorylation of the
      cytoplasmic domain of the type III receptor by the type II receptor. The type III
      receptor with the cytoplasmic domain deleted is able to bind TGF-beta, to bind
      the type II receptor, and to enhance TGF-beta binding to the type II receptor but
      is unable to enhance TGF-beta2 signaling, determining that the cytoplasmic domain
      is essential for some functions of the type III receptor. The type III receptor
      functions by selectively binding the autophosphorylated type II receptor via its
      cytoplasmic domain, thus promoting the preferential formation of a complex
      between the autophosphorylated type II receptor and the type I receptor and then
      dissociating from this active signaling complex. These studies, for the first
      time, elucidate important functional roles of the cytoplasmic domain of the type
      III receptor and demonstrate that these roles are essential for regulating TGF
      beta signaling.

PMID- 11323415
TI  - Novel role for JNK as a stress-activated Bcl2 kinase.
AB  - Interleukin (IL)-3-induced Bcl2 phosphorylation at Ser(70) may be required for
      its full and potent antiapoptotic activity. However, in the absence of IL-3,
      increased expression of Bcl2 can also prolong cell survival. To determine how
      Bcl2 may be functionally phosphorylated following IL-3 withdrawal, a stress
      activated Bcl2 kinase (SAK) was sought. Results indicate that anisomycin, a
      potent activator of the stress kinase JNK/SAPK, can induce Bcl2 phosphorylation
      at Ser(70) and that JNK1 can be latently activated following IL-3 withdrawal to
      mediate Bcl2 phosphorylation. JNK1 directly phosphorylates Bcl2 in vitro, co
      localizes with Bcl2, and collaborates with Bcl-2 to mediate prolonged cell
      survival in the absence of IL-3 or following various stress applications.
      Dominant-negative (DN)-JNK1 can block both anisomycin and latent IL-3 withdrawal
      induced Bcl2 phosphorylation (>90%) and potently enhances cell death.
      Furthermore, low dose okadaic acid (OA), a potent protein phosphatase 1 and 2A
      inhibitor, can activate the mitogen-activated protein kinases JNK1 and ERK1/2,
      but not p38 kinase, to induce Bcl2 phosphorylation and prolong cell survival in
      factor-deprived cells. Since PD98059, a specific MEK inhibitor, can only
      partially inhibit OA-induced Bcl2 phosphorylation but completely blocks OA
      induced Bcl2 phosphorylation in cells expressing DN-JNK1, this supports the
      conclusion that OA may stimulate Bcl2 phosphorylation via a mechanism involving
      both JNK1 and ERK1/2. Collectively, these findings indicate a novel role for JNK1
      as a SAK and may explain, at least in part, how functional phosphorylation of
      Bc12 can occur in the absence of growth factor.

PMID- 11323416
TI  - Identification of the substrate specificity-conferring amino acid residues of 4
      coumarate:coenzyme A ligase allows the rational design of mutant enzymes with new
      catalytic properties.
AB  - 4-Coumarate:coenzyme A ligases (4CLs) generally use, in addition to coumarate,
      caffeate and ferulate as their main substrates. However, the recently cloned
      Arabidopsis thaliana isoform At4CL2 is exceptional because it has no appreciable
      activity with ferulate. On the basis of information obtained from the crystal
      structure of the phenylalanine-activating domain of gramicidin S-synthetase, 10
      amino acid residues were identified that may form the substrate binding pocket of
      4CL. Among these amino acids, representing the putative "substrate specificity
      motif," only one residue, Met(293), was not conserved in At4CL2, compared with
      At4CL1 and At4CL3, two isoforms using ferulate. Substitution of Met(293) or
      Lys(320), another residue of the putative substrate specificity motif, which in
      the predicted three-dimensional structure is located in close proximity to
      Met(293), by smaller amino acids converted At4CL2 to an enzyme capable of using
      ferulate. The activity with caffeate was not or only moderately affected.
      Conversely, substitution of Met(293) by bulky aromatic amino acids increased the
      apparent affinity (K(m)) for caffeate up to 10-fold, whereas single substitutions
      of Val(294) did not affect substrate use. The results support our structural
      assumptions and suggest that the amino acid residues 293 and 320 of At4CL2
      directly interact with the 3-methoxy group of the phenolic substrate and
      therefore allow a first insight into the structural principles determining
      substrate specificity of 4CL.

PMID- 11323417
TI  - A specific isozyme of 2'-5' oligoadenylate synthetase is a dual function
      proapoptotic protein of the Bcl-2 family.
AB  - 2-5(A) synthetases are a family of interferon-induced enzymes that polymerize ATP
      into 2'-5' linked oligoadenylates that activate RNase L and cause mRNA
      degradation. Because they all can synthesize 2-5(A), the reason for the existence
      of so many synthetase isozymes is unclear. Here we report that the 9-2 isozyme of
      2-5(A) synthetase has an additional activity: it promotes apoptosis in mammalian
      cells. The proapoptotic activity of 9-2 was isozyme-specific and enzyme activity
      independent. The 9-2-expressing cells exhibited many properties of cells
      undergoing apoptosis, such as DNA fragmentation, caspase activation, and poly ADP
      ribose polymerase and lamin B cleavage. The isozyme-specific carboxyl-terminal
      tail of the 9-2 protein was shown, by molecular modeling, to contain a Bcl-2
      homology 3 (BH3) domain, suggesting that it may be able to interact with members
      of the Bcl-2 family that contain BH1 and BH2 domains. Co-immunoprecipitate assays
      and confocal microscopy showed that 9-2 can indeed interact with the anti
      apoptotic proteins Bcl-2 and Bclx(L) in vivo and in vitro. Mutations in the BH3
      domain that eliminated the 9-2-Bcl-2 amd 9-2-Bclx(L) interactions also eliminated
      the apoptotic activity of 9-2. Thus, we have identified an interferon-induced
      dual function protein of the Bcl-2 family that can synthesize 2-5(A) and promote
      cellular apoptosis independently. Moreover, the cellular abundance of this
      protein is regulated by alternative splicing; the other isozymes encoded by the
      same gene are not proapoptotic.

PMID- 11323418
TI  - Palmitoylation of CCR5 is critical for receptor trafficking and efficient
      activation of intracellular signaling pathways.
AB  - CCR5 is a CC chemokine receptor expressed on memory lymphocytes, macrophages, and
      dendritic cells and also constitutes the main coreceptor for macrophage-tropic
      (or R5) strains of human immunodeficiency viruses. In the present study, we
      investigated whether CCR5 was palmitoylated in its carboxyl-terminal domain by
      generating alanine substitution mutants for the three cysteine residues present
      in this region, individually or in combination. We found that wild-type CCR5 was
      palmitoylated, but a mutant lacking all three Cys residues was not. Through the
      use of green fluorescent fusion proteins and immunofluorescence studies, we found
      that the absence of receptor palmitoylation resulted in sequestration of CCR5 in
      intracellular biosynthetic compartments. By using the fluorescence recovery after
      photobleaching technique, we showed that the non-palmitoylated mutant had
      impaired diffusion properties within the endoplasmic reticulum. We next studied
      the ability of the mutants to bind and signal in response to chemokines.
      Chemokines binding and activation of G(i)-mediated signaling pathways, such as
      calcium mobilization and inhibition of adenylate cyclase, were not affected.
      However, the duration of the functional response, as measured by a
      microphysiometer, and the ability to increase [(35)S]guanosine 5'-3-O
      (thio)triphosphate binding to membranes were severely affected for the non
      palmitoylated mutant. The ability of RANTES (regulated on activation normal T
      cell expressed and secreted) and aminooxypentane-RANTES to promote CCR5
      endocytosis was not altered by cysteine replacements. Finally, we found that the
      absence of receptor palmitoylation reduced the human immunodeficiency viruses
      coreceptor function of CCR5, but this effect was secondary to the reduction in
      surface expression. In conclusion, we found that palmitoylated cysteines play an
      important role in the intracellular trafficking of CCR5 and are likely necessary
      for efficient coupling of the receptor to part of its repertoire of signaling
      cascades.

PMID- 11323419
TI  - Molecular cloning, genomic mapping, and expression of two secretor blood group
      alpha (1,2)fucosyltransferase genes differentially regulated in mouse uterine
      epithelium and gastrointestinal tract.
AB  - Fucosylated oligosaccharides have been proposed to be involved in multiple cell
      cell interactions, including mouse blastocyst adhesion and intestine-microbe
      interactions. To begin to define the regulation and function of terminal
      alpha(1,2)fucosylated carbohydrates in these and other tissues, we isolated and
      characterized a 85-kilobase (kb) genomic region of mouse chromosome 7, 23.2
      centimorgans analogous to human chromosome 19q13.3 that encodes three
      alpha(1,2)fucosyltransferases. Gene-specific DNA probes from the open reading
      frames of the mouse fucosyltransferase genes corresponding to human FUT1, FUT2,
      and SEC1 demonstrate distinct tissue-specific expression patterns by Northern
      blot analyses. Flow cytometry profiles of cultured cells transfected with DNA
      segments containing the open reading frames of the mouse genes confirm that each
      encodes an alpha(1,2)fucosyltransferase. In uterus and colon, a 3.3-kb FUT2 mRNA
      represents the major fucosyltransferase gene expressed. Steady-state FUT2 mRNA
      levels are cyclically regulated during the estrus cycle, increasing 10-fold from
      early diestrus to a relative maximum in proestrus. In contrast, SEC1 and FUT1 do
      not show prominently regulated expression in uterus. FUT2 expression localizes to
      luminal uterine epithelium by in situ hybridization, implying that this gene
      determines expression of cell surface Fucalpha1-->2Galbeta epitopes proposed to
      mediate blastocyst adhesion.

PMID- 11323420
TI  - Defective fatty acid uptake in the spontaneously hypertensive rat is a primary
      determinant of altered glucose metabolism, hyperinsulinemia, and myocardial
      hypertrophy.
AB  - Genetic linkage studies implicated deficiency of CD36, a membrane fatty acid (FA)
      transporter, in the hypertriglyceridemia and hyperinsulinemia of the
      spontaneously hypertensive rat (SHR). In this study we determined whether loss of
      CD36 function in FA uptake is a primary determinant of the SHR phenotype. In
      vivo, tissue distribution of iodinated, poorly oxidized beta-methyliodophenyl
      pentadecanoic acid (BMIPP) was examined 2 h after its intravenous injection.
      Fatty acid transport was also measured in vitro over 20 to 120 s in isolated
      adipocytes and cardiomyocytes obtained from SHR and from a congenic line
      (SHRchr4) that incorporates a piece of chromosome 4 containing wild-type CD36.
      SHR heart and adipose tissue exhibited defects in FA uptake and in conversion of
      diglycerides to triglycerides that are similar to those observed in the CD36 null
      mouse. However, a key difference in SHR tissues is that fatty acid oxidation is
      much more severely impaired than fatty acid esterification, which may underlie
      the 4-5-fold accumulation of free BMIPP measured in SHR muscle. Studies with
      isolated adipocytes and cardiomyocytes directly confirmed both the defect in FA
      transport and the fact that it is underestimated by BMIPP. Heart, oxidative
      muscle, and adipose tissue in the SHR exhibited a large increase in glucose
      uptake measured in vivo using [(18)F]fluorodeoxyglucose. Supplementation of the
      diet with short-chain fatty acids, which do not require CD36-facilitated
      transport, eliminated the increase in glucose uptake, the hyperinsulinemia, and
      the heart hypertrophy in the SHR. This indicated that lack of metabolic energy
      consequent to deficient FA uptake is the primary defect responsible for these
      abnormalities. Hypertension was not alleviated by the supplemented diet
      suggesting it is unrelated to fuel supply and any contribution of CD36 deficiency
      to this trait may be more complex to determine. It may be worth exploring whether
      short-chain FA supplementation can reverse some of the deleterious effects of
      CD36 deficiency in humans, which may include hypertrophic cardiomyopathy.

PMID- 11323421
TI  - Cyclosporin A inhibits inositol 1,4,5-trisphosphate-dependent Ca2+ signals by
      enhancing Ca2+ uptake into the endoplasmic reticulum and mitochondria.
AB  - Cytosolic Ca(2+) ([Ca(2+)](i)) oscillations may be generated by the inositol
      1,4,5-trisphosphate receptor (IP(3)R) driven through cycles of
      activation/inactivation by local Ca(2+) feedback. Consequently, modulation of the
      local Ca(2+) gradients influences IP(3)R excitability as well as the duration and
      amplitude of the [Ca(2+)](i) oscillations. In the present work, we demonstrate
      that the immunosuppressant cyclosporin A (CSA) reduces the frequency of IP(3)
      dependent [Ca(2+)](i) oscillations in intact hepatocytes, apparently by altering
      the local Ca(2+) gradients. Permeabilized cell experiments demonstrated that CSA
      lowers the apparent IP(3) sensitivity for Ca(2+) release from intracellular
      stores. These effects on IP(3)-dependent [Ca(2+)](i) signals could not be
      attributed to changes in calcineurin activity, altered ryanodine receptor
      function, or impaired Ca(2+) fluxes across the plasma membrane. However, CSA
      enhanced the removal of cytosolic Ca(2+) by sarco-endoplasmic reticulum Ca(2+)
      ATPase (SERCA), lowering basal and inter-spike [Ca(2+)](i). In addition, CSA
      stimulated a stable rise in the mitochondrial membrane potential (DeltaPsi(m)),
      presumably by inhibiting the mitochondrial permeability transition pore, and this
      was associated with increased Ca(2+) uptake and retention by the mitochondria
      during a rise in [Ca(2+)](i). We suggest that CSA suppresses local Ca(2+)
      feedback by enhancing mitochondrial and endoplasmic reticulum Ca(2+) uptake,
      these actions of CSA underlie the lower IP(3) sensitivity found in permeabilized
      cells and the impaired IP(3)-dependent [Ca(2+)](i) signals in intact cells. Thus,
      CSA binding proteins (cyclophilins) appear to fine tune agonist-induced
      [Ca(2+)](i) signals, which, in turn, may adjust the output of downstream Ca(2+)
      sensitive pathways.

PMID- 11323422
TI  - Characterization of a 2',5'-oligoadenylate (2-5A)-dependent 37-kDa RNase L: azido
      photoaffinity labeling and 2-5A-dependent activation.
AB  - Upregulation of key components of the 2',5'-oligoadenylate (2-5A)
      synthetase/RNase L pathway has been identified in extracts of peripheral blood
      mononuclear cells from individuals with chronic fatigue [corrected] syndrome,
      including the presence of a low molecular weight form of RNase L. In this study,
      analysis of 2',5'-Oligoadenylate (2-5A) binding and activation of the 80- and 37
      kDa forms of RNase L has been completed utilizing
      photolabeling/immunoprecipitation and affinity assays, respectively. Saturation
      of photolabeling of the 80- and the 37-kDa RNase L with the 2-5A azido
      photoprobe, [(32)P]pApAp(8-azidoA), was achieved. Half-maximal photoinsertion of
      [(32)P]pApAp(8-azidoA) occurred at 3.7 x 10(-8) m for the 80-kDa RNase L and at
      6.3 x 10(-8) m for the 37-kDa RNase L. Competition experiments using 100-fold
      excess unlabeled 2-5A photoaffinity probe, pApAp(8-azidoA), and authentic 2-5A
      (p(3)A(3)) resulted in complete protection against photolabeling, demonstrating
      that [(32)P]pApAp(8-azidoA) binds specifically to the 2-5A-binding site of the 80
      and 37-kDa RNase L. The rate of RNA hydrolysis by the 37-kDa RNase L was three
      times faster than the 80-kDa RNase L. The data obtained from these 2-5A binding
      and 2-5A-dependent activation studies demonstrate the utility of [(32)P]pApAp(8
      azidoA) for the detection of the 37-kDa RNase L in peripheral blood mononuclear
      cell extracts.

PMID- 11323423
TI  - Compound effects of point mutations causing campomelic dysplasia/autosomal sex
      reversal upon SOX9 structure, nuclear transport, DNA binding, and transcriptional
      activation.
AB  - Human mutations in the transcription factor SOX9 cause campomelic
      dysplasia/autosomal sex reversal. Here we identify and characterize two novel
      heterozygous mutations, F154L and A158T, that substitute conserved "hydrophobic
      core" amino acids of the high mobility group domain at positions thought to
      stabilize SOX9 conformation. Circular dichroism studies indicated that both
      mutations disrupt alpha-helicity within their high mobility group domain, whereas
      tertiary structure is essentially maintained as judged by fluorescence
      spectroscopy. In cultured cells, strictly nuclear localization was observed for
      wild type SOX9 and the F154L mutant; however, the A158T mutant showed a 2-fold
      reduction in nuclear import efficiency. Importin-beta was demonstrated to be the
      nuclear transport receptor recognized by SOX9, with both mutant proteins binding
      importin-beta with wild type affinity. Whereas DNA bending was unaffected, DNA
      binding was drastically reduced in both mutants (to 5% of wild type activity in
      F154L, 17% in A158T). Despite this large effect, transcriptional activation in
      cultured cells was only reduced to 26% in F154L and 62% in A158T of wild type
      activity, suggesting that a small loss of SOX9 transactivation activity could be
      sufficient to disrupt proper regulation of target genes during bone and testis
      formation. Thus, clinically relevant mutations of SOX9 affect protein structure
      leading to compound effects of reduced nuclear import and reduced DNA binding,
      the net effect being loss of transcriptional activation.

PMID- 11323424
TI  - Coordinate control of sphingolipid biosynthesis and multidrug resistance in
      Saccharomyces cerevisiae.
AB  - Multiple or pleiotropic drug resistance often occurs in the yeast Saccharomyces
      cerevisiae through genetic activation of the Cys(6)-Zn(II) transcription factors
      Pdr1p and Pdr3p. Hyperactive alleles of these proteins cause overproduction of
      target genes that include drug efflux pumps, which in turn confer high level drug
      resistance. Here we provide evidence that both Pdr1p and Pdr3p act to regulate
      production of an enzyme involved in sphingolipid biosynthesis in S. cerevisiae.
      The last step in formation of the major sphingolipid in the yeast plasma
      membrane, mannosyldiinositol phosphorylceramide, is catalyzed by the product of
      the IPT1 gene, inositol phosphotransferase (Ipt1p). Transcription of the IPT1
      gene is responsive to changes in activity of Pdr1p and Pdr3p. A single
      Pdr1p/Pdr3p response element is present in the IPT1 promoter and is required for
      regulation by these factors. Loss of IPT1 has complex effects on drug resistance
      of the resulting strain, consistent with an important role for mannosyldiinositol
      phosphorylceramide in normal plasma membrane function. Direct assay for lipid
      contents of cells demonstrates that changes in sphingolipid composition correlate
      with changes in the activity of Pdr3p. These data suggest that Pdr1p and Pdr3p
      may act to modulate the lipid composition of membranes in S. cerevisiae through
      activation of sphingolipid biosynthesis along with other target genes.

PMID- 11323425
TI  - Topoisomerase II from Chlorella virus PBCV-1 has an exceptionally high DNA
      cleavage activity.
AB  - Chlorella virus PBCV-1 topoisomerase II is the only functional type II enzyme
      known to be encoded by a virus that infects eukaryotic cells. However, it has not
      been established whether the protein is expressed following viral infection or
      whether the enzyme has any catalytic features that distinguish it from cellular
      type II topoisomerases. Therefore, the present study characterized the
      physiological expression of PBCV-1 topoisomerase II and individual reaction steps
      catalyzed by the enzyme. Results indicate that the topoisomerase II gene is
      widely distributed among Chlorella viruses and that the protein is expressed 60
      90 min after viral infection of algal cells. Furthermore, the enzyme has an
      extremely high DNA cleavage activity that sets it apart from all known eukaryotic
      type II topoisomerases. Levels of DNA scission generated by the viral enzyme are
      approximately 30 times greater than those observed with human topoisomerase
      IIalpha. The high levels of cleavage are not due to inordinately tight enzyme-DNA
      binding or to impaired DNA religation. Thus, they most likely reflect an elevated
      forward rate of scission. The robust DNA cleavage activity of PBCV-1
      topoisomerase II provides a unique tool for studying the catalytic functions of
      type II topoisomerases.

PMID- 11323426
TI  - Down-regulation of lysyl oxidase-induced tumorigenic transformation in NRK-49F
      cells characterized by constitutive activation of ras proto-oncogene.
AB  - Several investigations have suggested a putative tumor suppressor role for lysyl
      oxidase because it is down-regulated in many human and oncogene-induced tumors.
      To address this issue we down-regulated the enzyme in normal rat kidney
      fibroblasts by stable transfection of its cDNA in an antisense orientation. The
      selected clones revealed an absence of lysyl oxidase and dramatic phenotypic
      changes, interpretable as signs of transformation. The antisense lysyl oxidase
      clones showed, indeed, loose attachment to the plate and anchorage-independent
      growth and were highly tumorigenic in nude mice. Moreover, we found an impaired
      response of the PDGF and IGF-1 receptors to their ligands. In particular, the
      transformed cells showed a down-regulation of both PDGF receptors and expressed
      the 105-kDa isoform of the IGF-1 beta receptor, which was not present in the
      normal control cells. The lack of response to PDGF-BB has been described as a
      feature of many ras-transformed phenotypes. Therefore, we looked at the status of
      the p21(ras). Indeed, we found a significantly higher level of active p21(ras)
      both during steady-state growth and prolonged starvation. Our data reveal new
      evidence for a tumor suppressor activity of lysyl oxidase, highlighting its
      particular role in controlling Ras activation and growth factor dependence.

PMID- 11323428
TI  - Mechanism and requirements for bovine papillomavirus, type 1, E1 initiator
      complex assembly promoted by the E2 transcription factor bound to distal sites.
AB  - DNA replication of papillomavirus requires the viral initiator E1 and the
      transcription factor E2. Bovine papillomavirus, type 1 (BPV-1), E1, and E2 bind
      cooperatively as dimers to proximal sites in the viral replicator generating a
      sequence-specific E1E2-ori complex. This complex is critical for replication and
      can be converted to a multimeric E1-ori initiator complex by displacement of E2
      in the presence of hydrolyzable ATP. However, E2 can function over extended
      distances, and E2 at a distal position 33 base pairs upstream of the E1-binding
      site also loads an E1 dimer onto ori. Under these conditions, neither
      displacement of E2 nor ATP hydrolysis are required for E1-ori formation,
      consistent with a need for ATP hydrolysis in E2 displacement from E1E2-ori.
      However, ATP is required for stabilization of the resulting E1-ori complex. These
      results indicate that BPV (with a proximal E2-binding site) and human
      papillomaviruses (with distal E2-binding sites) utilize the same general
      mechanism for E1 loading but suggest that E1E2-ori, which forms preferentially on
      ori, may perform an additional role in BPV replication.

PMID- 11323427
TI  - Increased production of apolipoprotein B-containing lipoproteins in the absence
      of hyperlipidemia in transgenic mice expressing cholesterol 7alpha-hydroxylase.
AB  - The finding that expression of a cholesterol 7alpha-hydroxylase (CYP7A1)
      transgene in cultured rat hepatoma cells caused a coordinate increase in
      lipogenesis and secretion of apoB-containing lipoproteins led to the hypothesis
      that hepatic production of apoB-containing lipoproteins may be linked to the
      expression of CYP7A1 (Wang, S.-L., Du, E., Martin, T. D., and Davis, R. A. (1997)
      J. Biol. Chem. 272, 19351-19358). To examine this hypothesis in vivo, a transgene
      encoding CYP7A1 driven by the constitutive liver-specific enhancer of the human
      apoE gene was expressed in C56BL/6 mice. The expression of CYP7A1 mRNA (20-fold),
      protein ( approximately 10-fold), and enzyme activity (5-fold) was markedly
      increased in transgenic mice compared with non-transgenic littermates. The bile
      acid pool of CYP7A1 transgenic mice was doubled mainly due to increased
      hydrophobic dihydroxy bile acids. In CYP7A1 transgenic mice, livers contained
      approximately 3-fold more sterol response element-binding protein-2 mRNA. Hepatic
      expression of mRNAs encoding lipogenic enzymes (i.e. fatty-acid synthase, acetyl
      CoA carboxylase, stearoyl-CoA desaturase, squalene synthase, farnesyl
      pyrophosphate synthase, 3-hydroxy-3-methylglutaryl-CoA reductase, and low density
      lipoprotein receptor) as well as microsomal triglyceride transfer protein were
      elevated approximately 3-5-fold in transgenic mice. CYP7A1 transgenic mice also
      displayed a >2-fold increase in hepatic production and secretion of triglyceride
      rich apoB-containing lipoproteins. Despite the increased hepatic secretion of
      apoB-containing lipoproteins in CYP7A1 mice, plasma levels of triglycerides and
      cholesterol were not significantly increased. These data suggest that the 5-fold
      increased expression of the low density lipoprotein receptor displayed by the
      livers of CYP7A1 transgenic mice was sufficient to compensate for the 2-fold
      increase production of apoB-containing lipoproteins. These findings emphasize the
      important homeostatic role that CYP7A1 plays in balancing the anabolic
      lipoprotein assembly/secretion pathway with the cholesterol catabolic bile acid
      synthetic pathway.

PMID- 11323430
TI  - Role of the cytosolic phospholipase A2-linked cascade in signaling by an
      oncogenic, constitutively active Ha-Ras isoform.
AB  - Activation of Ras signaling by growth factors has been associated with gene
      regulation and cell proliferation. Here we characterize the contributory role of
      cytosolic phospholipase A(2) in the oncogenic Ha-Ras(V12) signaling pathway
      leading to activation of c-fos serum response element (SRE) and transformation in
      Rat-2 fibroblasts. Using a c-fos SRE-luciferase reporter gene, we showed that the
      transactivation of SRE by Ha-Ras(V12) is mainly via a Rac-linked cascade,
      although the Raf-mitogen-activated protein kinase cascade is required for full
      activation. In addition, Ha-Ras(V12)-induced DNA synthesis was significantly
      attenuated by microinjection of recombinant Rac(N17), a dominant negative mutant
      of Rac1. To identify the mediators downstream of Rac in the Ha-Ras(V12)
      signaling, we investigated the involvement of cytosolic phospholipase A(2).
      Oncogenic Ha-Ras(V12)-induced SRE activation was significantly inhibited by
      either pretreatment with mepacrine, a phospholipase A(2) inhibitor, or
      cotransfection with the antisense oligonucleotide of cytosolic phospholipase
      A(2). We also found cytosolic phospholipase A(2) to be situated downstream of Ha
      Ras(V12) in a signal pathway leading to transformation. Together, these results
      are indicative of mediatory roles of Rac and cytosolic phospholipase A(2) in the
      signaling pathway by which Ha-Ras(V12) transactivates c-fos SRE and
      transformation. Our findings point to cytosolic phospholipase A(2) as a novel
      potential target for suppressing oncogenic Ha-Ras(V12) signaling in the cell.

PMID- 11323429
TI  - BCR-ABL and interleukin 3 promote haematopoietic cell proliferation and survival
      through modulation of cyclin D2 and p27Kip1 expression.
AB  - Although it is evident that BCR-ABL can rescue cytokine-deprived hematopoietic
      progenitor cells from cell cycle arrest and apoptosis, the exact mechanism of
      action of BCR/ABL and interleukin (IL)-3 to promote proliferation and survival
      has not been established. Using the pro-B cell line BaF3 and a BaF3 cell line
      stably overexpressing BCR-ABL (BaF3-p210), we investigated the proliferative
      signals derived from BCR-ABL and IL-3. The results indicate that both IL-3 and
      BCR-ABL target the expression of cyclin Ds and down-regulation of p27(Kip1) to
      mediate pRB-related pocket protein phosphorylation, E2F activation, and thus S
      phase progression. These findings were further confirmed in a BaF3 cell line
      (TonB.210) where the BCR-ABL expression is inducible by doxycyclin and by using
      the drug STI571 to inactivate BCR-ABL activity in BaF3-p210. To establish the
      functional significance of cyclin D2 and p27(Kip1) expression in response to IL-3
      and BCR-ABL expression, we studied the effects of ectopic expression of cyclin D2
      and p27(Kip1) on cell proliferation and survival. Our results demonstrate that
      both cyclin D2 and p27(Kip1) have a role in BaF3 cell proliferation and survival,
      as ectopic expression of cyclin D2 is sufficient to abolish the cell cycle arrest
      and apoptosis induced by IL-3 withdrawal or by BCR-ABL inactivation, while
      overexpression of p27(Kip1) can cause cell cycle arrest and apoptosis in the BaF3
      cells. Furthermore, our data also suggest that cyclin D2 functions upstream of
      p27(Kip1), cyclin E, and cyclin D3, and therefore, plays an essential part in
      integrating the signals from IL-3 and BCR-ABL with the pRB/E2F pathway.

PMID- 11323431
TI  - Site-specific charge interactions of alpha-conotoxin MI with the nicotinic
      acetylcholine receptor.
AB  - We have tested the importance of charge interactions for alpha-conotoxin MI
      binding to the nicotinic acetylcholine receptor (AChR). Ionic residues on alpha
      conotoxin MI were altered by site-directed mutagenesis or by chemical
      modification. In physiological buffer, removal of charges at the N terminus, His
      5, and Lys-10 had small (2-4-fold) effects on binding affinity to the mouse
      muscle AChR and the Torpedo AChR. It was also demonstrated that conotoxin had no
      effect on the conformational equilibrium of either receptor, as assessed by the
      effects of the noncompetitive antagonist proadifen on conotoxin binding and,
      conversely, the effect of conotoxin on the affinity of phencyclidine, proadifen,
      and ethidium. Conotoxin displayed higher binding affinity in low ionic strength
      buffer; neutralization of Lys-10 and the N terminus by acetylation blocked this
      affinity shift at the alphadelta site but not at the alphagamma site. It is
      concluded that Ctx residues Lys-10 and the N terminal interact with oppositely
      charged receptor residues only at the alphadelta site, and the two sites have
      distinct arrangements of charged residues. Ethidium fluorescence experiments
      demonstrated that conotoxin is formally competitive with a small cholinergic
      ligand, tetramethylammonium. Thus, alpha-conotoxin MI appears to interact with
      the portion of the binding site responsible for stabilizing agonist cations but
      does not do so with a cationic residue and is, consequently, incapable of
      inducing a conformational change.

PMID- 11323432
TI  - Characterization of insulin-like growth factor I (IGF-I) receptor mutants for
      their effects on IGF-I- and interleukin 4-mediated DNA synthesis of 32D cells.
AB  - Recently we demonstrated that overexpression of the wild type insulin-like growth
      factor I receptor (IGF-IRWT) in 32D myeloid progenitor cells led to cell
      proliferation in response to interleukin 4 (IL-4) as well as insulin-like growth
      factor I (IGF-I) in the absence of insulin receptor substrate expression (Soon,
      L., Flechner, L., Gutkind, J. S., Wang, L. H., Baserga, R., Pierce, J. H., and
      Li, W. (1999) Mol. Cell. Biol. 19, 3816-3828). To understand the structural
      importance of insulin-like growth factor I receptor (IGF-IR) in mediating IL-4-
      and IGF-I-induced DNA synthesis, we transfected various mutants of IGF-IR to 32D
      cells. Our results show that most mutants, including Y1250F, Y1251F,
      Y1250F/Y1251F, S1280A/S1281A/S1282A/S1283A, Y1316F, and 1245d, still retained
      mitogenic response toward IGF-I or IL-4. However, the Y950F, Y1131F, and Y1135F
      mutants were not able to respond to either ligand. The H1293F/K1294R and 1293d
      mutants reduced response toward IGF-I but not to IL-4. Phosphorylation of Shc was
      greatly reduced in those three mutants that lost mitogenic response. The MAPK
      activity was much lower in Y1131F and Y1135F mutants, indicating the importance
      of the Shc/MAPK pathway in IGF-I-induced mitogenesis. Importantly, the
      synergistic effect of these two factors on DNA synthesis was not affected in
      cells expressing most of the mutants, even in those three that had lower
      mitogenic response toward a single ligand. These results suggest that an
      unidentified pathway(s) may be induced upon co-addition of IGF-I and IL-4 that
      sustains the intact mitogenesis.

PMID- 11323433
TI  - Assembly of the human origin recognition complex.
AB  - The six-subunit origin recognition complex (ORC) was originally identified in the
      yeast Saccharomyces cerevisiae. Yeast ORC binds specifically to origins of
      replication and serves as a platform for the assembly of additional initiation
      factors, such as Cdc6 and the Mcm proteins. Human homologues of all six ORC
      subunits have been identified by sequence similarity to their yeast counterparts,
      but little is known about the biochemical characteristics of human ORC (HsORC).
      We have extracted HsORC from HeLa cell chromatin and probed its subunit
      composition using specific antibodies. The endogenous HsORC, identified in these
      experiments, contained homologues of Orc1-Orc5 but lacked a putative homologue of
      Orc6. By expressing HsORC subunits in insect cells using the baculovirus system,
      we were able to identify a complex containing all six subunits. To explore the
      subunit-subunit interactions that are required for the assembly of HsORC, we
      carried out extensive co-immunoprecipitation experiments with recombinant ORC
      subunits expressed in different combinations. These studies revealed the
      following binary interactions: HsOrc2-HsOrc3, HsOrc2-HsOrc4, HsOrc3-HsOrc4,
      HsOrc2-HsOrc6, and HsOrc3-HsOrc6. HsOrc5 did not form stable binary complexes
      with any other HsORC subunit but interacted with sub-complexes containing any two
      of subunits HsOrc2, HsOrc3, or HsOrc4. Complex formation by HsOrc1 required the
      presence of HsOrc2, HsOrc3, HsOrc4, and HsOrc5 subunits. These results suggest
      that the subunits HsOrc2, HsOrc3, and HsOrc4 form a core upon which the ordered
      assembly of HsOrc5 and HsOrc1 takes place. The characterization of HsORC should
      facilitate the identification of human origins of DNA replication.

PMID- 11323434
TI  - An evolutionarily conserved motif in the TAB1 C-terminal region is necessary for
      interaction with and activation of TAK1 MAPKKK.
AB  - TAK1, a member of the MAPKKK family, is involved in the intracellular signaling
      pathways mediated by transforming growth factor beta, interleukin 1, and Wnt.
      TAK1 kinase activity is specifically activated by the TAK1-binding protein TAB1.
      The C-terminal 68-amino acid sequence of TAB1 (TAB1-C68) is sufficient for TAK1
      interaction and activation. Analysis of various truncated versions of TAB1-C68
      defined a C-terminal 30-amino acid sequence (TAB1-C30) necessary for TAK1 binding
      and activation. NMR studies revealed that the TAB1-C30 region has a unique alpha
      helical structure. We identified a conserved sequence motif, PYVDXA/TXF, in the C
      terminal domain of mammalian TAB1, Xenopus TAB1, and its Caenorhabditis elegans
      homolog TAP-1, suggesting that this motif constitutes a specific TAK1 docking
      site. Alanine substitution mutagenesis showed that TAB1 Phe-484, located in the
      conserved motif, is crucial for TAK1 binding and activation. The C. elegans
      homolog of TAB1, TAP-1, was able to interact with and activate the C. elegans
      homolog of TAK1, MOM-4. However, the site in TAP-1 corresponding to Phe-484 of
      TAB1 is an alanine residue (Ala-364), and changing this residue to Phe abrogates
      the ability of TAP-1 to interact with and activate MOM-4. These results suggest
      that the Phe or Ala residue within the conserved motif of the TAB1-related
      proteins is important for interaction with and activation of specific TAK1 MAPKKK
      family members in vivo.

PMID- 11323435
TI  - Insulin-like growth factor 1 (IGF-1)-induced twist expression is involved in the
      anti-apoptotic effects of the IGF-1 receptor.
AB  - In this study we investigated the molecular mechanisms whereby insulin-like
      growth factor 1 (IGF-1) induced Twist gene expression and the role of Twist in
      the anti-apoptotic actions of the IGF-1 receptor. In NIH-3T3 fibroblasts
      overexpressing the human IGF-1 receptor (NWTb3), treatment with IGF-1 (10(-8) m)
      for 1 and 4 h increased the level of Twist mRNA as well as protein by 3-fold. In
      contrast, insulin at physiological concentrations did not stimulate Twist
      expression in NIH-3T3 fibroblasts overexpressing the human insulin receptor. The
      IGF-1 effect was specific for the IGF-1 receptor since, in cells overexpressing a
      dominant negative IGF-1 receptor, IGF-1 failed to increase Twist expression. Pre
      incubation with the ERK1/2 inhibitor U0126 or expression of a dominant negative
      MEK-1 abolished the effect of IGF-1 on Twist mRNA expression in NWTb3 cells,
      suggesting that Twist induction by IGF-1 occurs via the mitogen-activated protein
      kinase signaling pathway. In vivo, IGF-1 injection increased the mRNA level of
      Twist in mouse skeletal muscle, the major site of Twist expression. Finally,
      using an antisense strategy, we demonstrated that a reduction of 40% in Twist
      expression decreased significantly the ability of IGF-1 to rescue NWTb3 cells
      from etoposide-induced apoptosis. Taken together, these results define Twist as
      an important factor involved in the anti-apoptotic actions of the IGF-1 receptor.

PMID- 11323436
TI  - Ykt6 forms a SNARE complex with syntaxin 5, GS28, and Bet1 and participates in a
      late stage in endoplasmic reticulum-Golgi transport.
AB  - The yeast SNARE Ykt6p has been implicated in several trafficking steps, including
      vesicular transport from the endoplasmic reticulum (ER) to the Golgi, intra-Golgi
      transport, and homotypic vacuole fusion. The functional role of its mammalian
      homologue (Ykt6) has not been established. Using antibodies specific for
      mammalian Ykt6, it is revealed that it is found mainly in Golgi-enriched
      membranes. Three SNAREs, syntaxin 5, GS28, and Bet1, are specifically associated
      with Ykt6 as revealed by co-immunoprecipitation, suggesting that these four
      SNAREs form a SNARE complex. Double labeling of Ykt6 and the Golgi marker
      mannosidase II or the ER-Golgi recycling marker KDEL receptor suggests that Ykt6
      is primarily associated with the Golgi apparatus. Unlike the KDEL receptor, Ykt6
      does not cycle back to the peripheral ER exit sites. Antibodies against Ykt6
      inhibit in vitro ER-Golgi transport of vesicular stomatitis virus envelope
      glycoprotein (VSVG) only when they are added before the EGTA-sensitive stage. ER
      Golgi transport of VSVG in vitro is also inhibited by recombinant Ykt6. In the
      presence of antibodies against Ykt6, VSVG accumulates in peri-Golgi vesicular
      structures and is prevented from entering the mannosidase II compartment,
      suggesting that Ykt6 functions at a late stage in ER-Golgi transport. Golgi
      apparatus marked by mannosidase II is fragmented into vesicular structures in
      cells microinjected with Ykt6 antibodies. It is concluded that Ykt6 functions in
      a late step of ER-Golgi transport, and this role may be important for the
      integrity of the Golgi complex.

PMID- 11323437
TI  - A functional nuclear localization sequence in the C-terminal domain of SHP-1.
AB  - The Src homology 2 domain-containing protein tyrosine phosphatases SHP-1 and SHP
      2 play an important role in many intracellular signaling pathways. Both SHP-1 and
      SHP-2 have been shown to interact with a diverse range of cytosolic and membrane
      bound signaling proteins. Generally, SHP-1 and SHP-2 perform opposing roles in
      signaling processes; SHP-1 acts as a negative regulator of transduction in
      hemopoietic cells, whereas SHP-2 acts as a positive regulator. Intriguingly, SHP
      1 has been proposed to play a positive regulating role in nonhemopoietic cells,
      although the mechanisms for this are not understood. Here we show that green
      fluorescent protein-tagged SHP-1 is unexpectedly localized within the nucleus of
      transfected HEK293 cells. In contrast, the highly related SHP-2 protein is more
      abundant within the cytoplasm of transfected cells. In accordance with this,
      endogenous SHP-1 is localized within the nucleus of several other nonhemopoietic
      cell types, whereas SHP-2 is distributed throughout the cytoplasm. In contrast,
      SHP-1 is confined to the cytoplasm of hemopoietic cells, with very little nuclear
      SHP-1 evident. Using chimeric SHP proteins and mutagenesis studies, the nuclear
      localization signal of SHP-1 was identified within the C-terminal domain of SHP-1
      and found to consist of a short cluster of basic amino acids (KRK). Although the
      KRK motif resembles half of a bipartite nuclear localization signal, it appears
      to function independently and is absolutely required for nuclear import. Our
      findings show that SHP-1 and SHP-2 are distinctly localized within nonhemopoietic
      cells, with the localization of SHP-1 differing dramatically between
      nonhemopoietic and hemopoietic cell lineages. This implies that SHP-1 nuclear
      import is a tightly regulated process and indicates that SHP-1 may possess novel
      nuclear targets.

PMID- 11323438
TI  - Kidney androgen-regulated protein interacts with cyclophilin B and reduces
      cyclosporine A-mediated toxicity in proximal tubule cells.
AB  - The gene for kidney androgen-regulated protein (KAP) is the most abundant and
      specific gene expressed in mouse kidney proximal tubule cells, where it is
      tightly regulated by steroid and thyroid hormones in different tubule segments.
      Despite the cell-specific expression, strict regulatory mechanisms, and relative
      abundance, nothing is known of the function of its encoded protein, which does
      not exhibit known structural or functional domains, or homologies with other
      sequences in the data bases. We raised monoclonal antibodies against KAP, which
      specifically recognize a protein with an apparent molecular mass of 20 kDa in
      crude kidney homogenates, the distribution and regulation of which parallel that
      of its mRNA. To gain insight into its function, we performed a yeast two hybrid
      screen and determined that KAP specifically interacts with cyclophilin B.
      Furthermore, cyclosporine A (CsA)-treated mice exhibited a significant decrease
      in KAP levels, and tetracycline-controlled overexpression of KAP in stably
      transfected proximal tubule cells significantly decreased the toxic effects of
      CsA. Taken together, these results indicate a functional relationship among KAP-,
      cyclophilin B-, and CsA-mediated nephrotoxicity and suggest an important role of
      KAP in renal physiology, providing new data on the molecular mechanisms implied
      in the toxic effects of CsA.

PMID- 11323439
TI  - A new pathway for glucose-dependent insulinotropic polypeptide (GIP) receptor
      signaling: evidence for the involvement of phospholipase A2 in GIP-stimulated
      insulin secretion.
AB  - The hormone glucose-dependent insulinotropic polypeptide (GIP) is an important
      regulator of insulin secretion. GIP has been shown to increase adenylyl cyclase
      activity, elevate intracellular Ca(2+) levels, and stimulate a mitogen-activated
      protein kinase pathway in the pancreatic beta-cell. In the current study we
      demonstrate a role for arachidonic acid in GIP-mediated signal transduction.
      Static incubations revealed that both GIP (100 nm) and ATP (5 microm)
      significantly increased [(3)H]arachidonic acid ([(3)H]AA) efflux from transfected
      Chinese hamster ovary K1 cells expressing the GIP receptor (basal, 128 +/- 11
      cpm/well; GIP, 212 +/- 32 cpm/well; ATP, 263 +/- 35 cpm/well; n = 4; p < 0.05).
      In addition, GIP receptors were shown for the first time to be capable of
      functionally coupling to AA production through Gbetagamma dimers in Chinese
      hamster ovary K1 cells. In a beta-cell model (betaTC-3), GIP was found to elicit
      [(3)H]AA release, independent of glucose, in a concentration-dependent manner
      (EC(50) value of 1.4 +/- 0.62 nm; n = 3). Although GIP did not potentiate insulin
      release under extracellular Ca(2+)-free conditions, it was still capable of
      elevating intracellular cAMP and stimulating [(3)H]AA release. Our data suggest
      that cAMP is the proximal signaling intermediate responsible for GIP-stimulated
      AA release. Finally, stimulation of GIP-mediated AA production was shown to be
      mediated via a Ca(2+)-independent phospholipase A(2). Arachidonic acid is
      therefore a new component of GIP-mediated signal transduction in the beta-cell.

PMID- 11323440
TI  - Molecular cloning and expression of a novel human beta-Gal-3-O-sulfotransferase
      that acts preferentially on N-acetyllactosamine in N- and O-glycans.
AB  - A novel cDNA-encoding galactose 3-O-sulfotransferase was cloned by screening the
      expressed sequence tag data base using the previously cloned cDNA encoding a
      galactosyl ceramide 3-O-sulfotransferase, which we term Gal3ST-1. The newly
      isolated cDNA encodes a novel 3-O-sulfotransferase, termed Gal3ST-3, that acts
      exclusively on N-acetyllactosamine present in N-glycans and core2-branched O
      glycans. These conclusions were confirmed by analyzing CD43 chimeric proteins in
      Chinese hamster ovary cells expressing core2 beta1,6-N
      acetylglucosaminyltransferase. The acceptor specificity of Gal3ST-3 contrasts
      with that of the recently cloned galactose 3-O-sulfotransferase (Honke, K.,
      Tsuda, M., Koyota, S., Wada, Y., Iida-Tanaka, N., Ishizuka, I., Nakayama, J., and
      Taniguchi, N. (2001) J. Biol. Chem. 276, 267-274), which we term Gal3ST-2 in the
      present study because the latter enzyme can also act on core1 O-glycan and type 1
      oligosaccharides, Galbeta1-->3GlcNAc. Moreover, Gal3ST-3 but not Gal3ST-2 can act
      on Galbeta1-->4(sulfo-->6)GlcNAc, indicating that disulfated sulfo-->3Galbeta1-
      >4(sulfo-->6) GlcNAc-->R may be formed by Gal3ST-3 in combination with GlcNAc 6-O
      sulfotransferase. Although both Gal3ST-2 and Gal3ST-3 do not act on galactosyl
      ceramide, Gal3ST-3 is only moderately more homologous to Gal3ST-2 (40.1%) than to
      Gal3ST-1 (38.0%) at the amino acid level. Northern blot analysis demonstrated
      that transcripts for Gal3ST-3 are predominantly expressed in the brain, kidney,
      and thyroid where the presence of 3'-sulfation of N-acetyllactosamine has been
      reported. These results indicate that the newly cloned Gal3ST-3 plays a critical
      role in 3'-sulfation of N-acetyllactosamine in both O- and N-glycans.

PMID- 11323441
TI  - A 49-residue peptide from adhesin F1 of Streptococcus pyogenes inhibits
      fibronectin matrix assembly.
AB  - F1 is an adhesin of Streptococcus pyogenes which binds the N-terminal 70-kDa
      region of fibronectin with high affinity. The fibronectin binding region of F1 is
      comprised of a 43-residue upstream domain and a repeat domain comprised of five
      tandem 37-residue sequences. We investigated the effects of these domains on the
      assembly of fibronectin matrix by human dermal fibroblasts, MG63 osteosarcoma
      cells, or fibroblasts derived from fibronectin-null stem cells. Subequimolar or
      equimolar concentrations of recombinant proteins containing both the upstream and
      repeat domains or just the repeat domain enhanced binding of fibronectin or its N
      terminal 70-kDa fragment to cell layers; higher concentrations of these
      recombinant proteins inhibited binding. The enhanced binding did not result in
      greater matrix assembly and was caused by increased ligand binding to substratum.
      In contrast, recombinant or synthetic protein containing the 43 residues of the
      upstream domain and the first 6 residues from the repeat domain exhibited
      monophasic inhibition with an IC(50) of approximately 10 nm. Truncation of the 49
      residue sequence at its N or C terminus caused loss of inhibitory activity. The
      49-residue upstream sequence blocked incorporation of both endogenous cellular
      fibronectin and exogenous plasma fibronectin into extracellular matrix and
      inhibited binding of 70-kDa fragment to fibronectin-null cells in a fibronectin
      free system. Inhibition of matrix assembly by the 49-mer had no effect on cell
      adhesion to substratum, cell growth, formation of focal contacts, or formation of
      stress fibers. These results indicate that the 49-residue upstream sequence of F1
      binds in an inhibitory mode to N-terminal parts of exogenous and endogenous
      fibronectin which are critical for fibronectin fibrillogenesis.

PMID- 11323442
TI  - Increasing fruit and vegetable intake and decreasing fat and sugar intake in
      families at risk for childhood obesity.
AB  - OBJECTIVE: The goal of this study was to evaluate the effect of a parent-focused
      behavioral intervention on parent and child eating changes and on percentage of
      overweight changes in families that contain at least one obese parent and a non
      obese child. RESEARCH METHODS AND PROCEDURES: Families with obese parents and non
      obese children were randomized to groups in which parents were provided a
      comprehensive behavioral weight-control program and were encouraged to increase
      fruit and vegetable intake or decrease intake of high-fat/high-sugar foods. Child
      materials targeted the same dietary changes as their parents without caloric
      restriction. RESULTS: Changes over 1 year showed that treatment influenced
      targeted parent and child fruit and vegetable intake and high-fat/high-sugar
      intake, with the Increase Fruit and Vegetable group also decreasing their
      consumption of high-fat/high-sugar foods. Parents in the increased fruit and
      vegetable group showed significantly greater decreases in percentage of
      overweight than parents in the decreased high-fat/high-sugar group. DISCUSSION:
      These results suggest that focusing on increasing intake of healthy foods may be
      a useful approach for nutritional change in obese parents and their children.

PMID- 11323443
TI  - Waist circumference and cardiovascular risk factors in prepubertal children.
AB  - OBJECTIVE: Intra-abdominal fat has been identified as being the most clinically
      relevant type of fat in humans. Therefore, an assessment of body-fat distribution
      could possibly identify subjects with the highest risk of adverse lipid profile
      and hypertension. Few data on the relationship between body-fat distribution and
      cardiovascular risk factors are available in children, especially before puberty.
      RESEARCH METHODS AND PROCEDURES: This cross-sectional study was undertaken to
      explore the relationship between anthropometric variables, lipid concentrations,
      and blood pressure (BP) in a sample of 818 prepubertal children (ages 3 to 11
      years) and to assess the clinical relevance of waist circumference in identifying
      prepubertal children with higher cardiovascular risk. Height, weight, triceps and
      subscapular skinfolds, waist circumference, and BP were measured. Plasma levels
      for triacylglycerol, total cholesterol, high-density lipoprotein (HDL)
      cholesterol, low-density lipoprotein cholesterol, apolipoprotein A1 (ApoA1), and
      apolipoprotein B (ApoB) were determined. RESULTS: Females were fatter than males
      (5.8 [3.5] vs. 4.8 [3.3] kg of fat mass; p < 0.01). Males had higher HDL
      cholesterol and ApoA1/ApoB plasma concentrations than females (p < 0.001 and p <
      0.01, respectively). Waist circumference had a higher correlation with systolic
      and diastolic BP (r = 0.40 and 0.29, respectively; p < 0.001) than triceps (r =
      0.35 and 0.21, respectively; p < 0.001) and subscapular (r = 0.28 and 0.16,
      respectively; p < 0.001) skinfolds and relative body weight (0.33 and 0.23,
      respectively; p < 0.001). Multivariate linear model analysis showed that
      ApoA1/ApoB, HDL cholesterol, total cholesterol/HDL cholesterol, and systolic as
      well as diastolic BP were significantly associated with waist circumference and
      triceps and subscapular skinfolds, independently of age, gender, and body mass
      index. DISCUSSION: Waist circumference as well as subscapular and triceps
      skinfolds may be helpful parameters in identifying prepubertal children with an
      adverse blood-lipids profile and hypertension. However, waist circumference,
      which is easy to measure and more easily reproducible than skinfolds, may be
      considered in clinical practice. Children with a waist circumference greater than
      the 90th percentile are more likely to have multiple risk factors than children
      with a waist circumference that is less than or equal to the 90th percentile.

PMID- 11323444
TI  - Blood pressure and pulse pressure during long-term weight loss in the obese: the
      Swedish Obese Subjects (SOS) Intervention Study.
AB  - OBJECTIVE: Recently we reported a complete relapse in the blood pressure (BP) of
      obese subjects despite a maintained 16% weight loss over 8 years. This relapse is
      now analyzed as a function of several variables. Pulse pressure (PP) is an
      independent risk factor of cardiovascular mortality. We now examine the
      development of PP in the obese and whether it can be modified by weight-reducing
      gastric surgery. RESEARCH METHODS AND PROCEDURES: A total of 1157 patients
      treated with gastric surgery and 1031 obese controls (body mass index of 41.0 +/-
      4.6 kg/m(2) [mean +/- SD], age 48 +/- 6 years) were followed for 5.5 +/- 2.1
      (range 3 to 10) years. To separate the effect of weight change from effect of
      time on BP, the patients were divided in cohorts based on follow-up time.
      RESULTS: Gastric surgery resulted in a maximum weight loss after 1 year that was
      followed by a moderate relapse. After 5.5 years, weight loss in the intervention
      group was 18 +/- 11% of initial body weight. Very little weight change was seen
      in controls. Systolic BP decreased in the intervention group during the first 6
      months but had relapsed to control values at last examination. The adjusted
      change in PP was +4.7 mm Hg in obese controls but +2.9 mm Hg in the intervention
      group (p < 0.001). Final BP values were more closely related to follow-up time
      and ongoing weight increase than to initial body weight or initial weight loss.
      DISCUSSION: Effects of time (aging) and weight change per year on BP can be
      separated. An early increase in PP could be observed in the obese. This increase
      could be modified by weight-reducing gastric surgery.

PMID- 11323445
TI  - Subclinical hypothyroidism in obese patients: relation to resting energy
      expenditure, serum leptin, body composition, and lipid profile.
AB  - OBJECTIVE: To evaluate whether subclinical hypothyroidism (SH) affects resting
      energy expenditure (REE) as well as body composition, lipid profile, and serum
      leptin in obese patients. RESEARCH METHODS AND PROCEDURES: A total of 108 obese
      patients with SH defined as normal free thyroxine levels and thyroid-stimulating
      hormone (TSH) values of > 4.38 microU/ml (mean +/- 2 SD of the values of our
      reference group of obese patients with normal thyroid function) were compared
      with a group of 131 obese patients matched for age, sex, and body mass index
      (BMI) but with normal TSH levels. We assessed estimated daily caloric intake by 7
      day recall, REE by indirect calorimetry, body composition by bioelectrical
      impedance analysis, serum leptin by radioimmunoassay, and lipid profile (i.e.,
      total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein
      cholesterol, and triglycerides). RESULTS: All of the variables measured were not
      different between the euthyroid obese patients and those with SH. In a multiple
      regression model with REE expressed for kilograms of fat free mass (REE/kgFFM) as
      a dependent variable and percentage of fat mass, BMI, waist-to-hip ratio, age,
      TSH, free thyroxine, serum leptin, and caloric intake as independent variables,
      only percentage of fat mass was significantly correlated with REE/kgFFM in both
      groups. In the SH group only, BMI, waist-to-hip ratio, age, and TSH were related
      to REE/kgFFM and explained 69.5% of its variability. After dividing the patients
      with SH using a cutoff TSH value of 5.7 microU/ml, which represents 3 SD above
      the mean of TSH levels of the group of obese patients with normal thyroid
      function, only REE/kgFFM was significantly different and lower in the group of
      more severely hypothyroid patients. DISCUSSION: In patients with obesity, SH
      affects energy expenditure only when TSH is clearly above the normal range; it
      does not change body composition and lipid profile. We suggest that, at least in
      obese patients, evaluation of TSH levels may be useful to rule out a possible
      impairment of resting energy expenditure due to a reduced peripheral effect of
      thyroid hormones.

PMID- 11323446
TI  - Daily oral oleoyl-estrone gavage induces a dose-dependent loss of fat in Wistar
      rats.
AB  - OBJECTIVE: To establish whether single daily oral doses of oleoyl-estrone result
      in dose-dependent slimming effects on normal weight rats, and to determine the
      changes in energy parameters induced by this treatment. RESEARCH METHODS AND
      PROCEDURES: The effects of a daily oral gavage of oleoyl-estrone (0, 0.2, 0.5, 1,
      2, 5, 10, and 20 micromol/kg per day) in 0.2 ml of sunflower oil given over a 10
      day period were studied in groups, each of which contained six adult female
      Wistar rats initially weighing 190 to 230 g. A group of intact control rats
      receiving no gavage was included for comparison. Body weight and food intake were
      measured daily. Rats were killed on day 10 of treatment, and body composition
      (protein nitrogen, lipids, and water), liver lipids, and plasma parameters
      (glucose, triacylglycerols, total cholesterol, free fatty acids, 3
      hydroxybutyrate, urea, aspartate, alanine transaminases, insulin, leptin, and
      free and acyl-estrone) were measured. RESULTS: The administration of oleoyl
      estrone resulted in a dose-dependent loss of body fat, because of a partly
      maintained energy expenditure combined with decreased food intake. The
      differences in the energy budget were met by internal fat pools. The changes
      recorded did not affect the levels of the main plasma energy homeostasis
      indicators: unaltered glucose, triacylglycerols, free fatty acids,
      3hydroxybutyrate, and urea. Protein was accrued even under conditions of severe
      lipid store drainage. There were no changes in transaminases. No lipid
      accumulation was recorded in the liver. Plasma insulin and leptin levels
      decreased with increased oleoyl-estrone doses, whereas the levels of free and
      esterified estrone increased with treatment, although not in proportion to the
      dose received. DISCUSSION: Oral treatment with oleoyl-estrone resulted in the
      specific dose-related loss of fat reserves with little change to other metabolic
      parameters. These results agree with the postulated role of oleoyl-estrone as a
      ponderostat signal.

PMID- 11323447
TI  - Body mass index and future healthcare costs: a retrospective cohort study.
AB  - OBJECTIVE: To assess the relationship between body mass index (BMI) and future
      healthcare costs. RESEARCH METHODS AND PROCEDURES: We undertook a retrospective
      cohort study of the relationship between obesity and future healthcare costs at
      Kaiser Permanente Northwest Division, a large health maintenance organization in
      Portland, Oregon. Study subjects (n = 1286) consisted of persons who responded to
      a 1990 health survey that was mailed to a random sample of adult Kaiser
      Permanente Northwest Division members who were 35 to 64 years of age; had a BMI >
      or = 20 kg/m(2) (based on self-reported height and weight); did not smoke
      cigarettes; and did not have a history of coronary heart disease, stroke, human
      immunodeficiency virus, or cancer. Subjects were stratified according to their
      BMI in 1990 (20 to 24.9, 25 to 29.9, and > or = 30 kg/m(2); n = 545, 474, and
      367, respectively). We then tallied their costs (in 1998 US dollars) for all
      inpatient care, outpatient services, and prescription drugs over a 9-year period
      (1990 through 1998). RESULTS: For persons with BMIs of 20 to 24.9 kg/m(2), mean
      (+/-SE) annual costs of prescription drugs, outpatient services, inpatient care,
      and all medical care averaged $261 (+/-18), $848 (+/-59), $532 (+/-85), and $1631
      (+/-120), respectively, over the study period. Cost ratios (95% confidence
      intervals) for persons with BMIs of 25 to 29.9 kg/m(2) and > or = 30 kg/m(2),
      respectively, were 1.37 (1.12 to 1.66) and 2.05 (1.62 to 2.55) for prescription
      drugs, 0.96 (0.83 to 1.13) and 1.14 (0.97 to 1.37) for outpatient services, 1.20
      (0.81 to 1.86) and 1.38 (0.91 to 2.14) for inpatient care, and 1.10 (0.91 to
      1.35) and 1.36 (1.11 to 1.68) for all medical care. DISCUSSION: Future healthcare
      costs are higher for persons who are overweight, especially those with BMIs > or
      = 30 kg/m(2).

PMID- 11323448
TI  - Defining the relationship between obesity and total joint arthroplasty.
AB  - OBJECTIVE: The purpose of this study was to examine the relationship between
      obesity and patient-administered outcome measures after total joint arthroplasty.
      RESEARCH METHODS AND PROCEDURES: A voluntary questionnaire-based registry
      contained 592 primary total hip arthroplasty patients and 1011 primary total knee
      arthroplasty patients with preoperative and 1-year data. Using logistic
      regression, the relationships between body mass index and the several outcome
      measures, including Short Form-36 and Western Ontario and McMaster Universities
      Osteoarthritis Index, were examined. RESULTS: There was no difference between
      obese and non-obese patients regarding satisfaction, decision to repeat surgery,
      and Delta physical component summary, Delta mental component summary, and Delta
      Western Ontario and McMaster Universities Osteoarthritis Index scores (p > 0.05
      for all). Body mass index was associated with an increased risk of having
      difficulty descending or ascending stairs at 1 year (odds ratio, 1.2 to 1.3).
      DISCUSSION: Obese patients enjoy as much improvement and satisfaction as other
      patients from total joint arthroplasty.

PMID- 11323449
TI  - Anti-lipolytic effects of insulin in African American and white prepubertal boys.
AB  - OBJECTIVE: Relative to whites, African Americans have lower circulating
      triglycerides (TG) and greater highdensity lipoprotein cholesterol. The metabolic
      basis for this difference is not known. This study was conducted to test the
      hypothesis that insulin-induced suppression of free fatty acids (FFA) results in
      lower serum TG in African American versus white prepubertal children. RESEARCH
      METHODS AND PROCEDURES: Insulin, FFA, and TG were determined at baseline and
      during a frequently sampled, intravenous glucose tolerance test in eight African
      American and eight white prepubertal males pair-matched for whole-body insulin
      sensitivity. RESULTS: Baseline TG was lower in African Americans (0.43 +/- 0.10
      vs. 0.79 +/- 0.37 mM/L; mean +/- SD; p < 0.01). African Americans had higher peak
      insulin (218 +/- 102 vs. 100 +/- 30 pM/L; mean +/- SD; p < 0.01) and a greater
      acute insulin response (9282 +/- 4272 vs. 4230 +/- 1326 pM/L x 10 minutes; mean
      +/- SD; p < 0.05). FFA and TG values determined at the FFA nadir were lower in
      African Americans (0.26 +/- 0.02 vs. 0.30 +/- 0.03 mEq/L; mean +/- SD; p < 0.01
      for FFA nadir and 0.49 +/- 0.07 vs. 0.77 +/- 0.33 mM/L; mean +/- SD; p < 0.05 for
      TG). Among all subjects, FFA nadir was correlated with peak insulin (r = -0.54; p
      < 0.05). After adjusting for FFA nadir, neither baseline nor postchallenge TG
      differed with ethnicity (p = 0.073 and 0.192, respectively). The ethnic
      difference in FFA nadir disappeared after adjusting for peak insulin (p = 0.073).
      DISCUSSION: These data suggest that hyperinsulinemiainduced suppression of FFA
      among African Americans is a determinant of lower TG in this group.

PMID- 11323450
TI  - Comparison of two software versions for assessment of body-composition analysis
      by DXA.
AB  - OBJECTIVE: To compare two software versions provided by Lunar CO: for assessment
      of body composition analysis by DXA. RESEARCH METHODS AND PROCEDURES: Soft-tissue
      phantoms for lean tissue (water) and fat tissue (methanol) were repeatedly
      scanned using DXA machines (DPX-L; Lunar CO., Madison, WI) and analyzed using
      software version 1.33 and the updated year 2000-compatible version 1.35. For the
      intersoftware comparison, the phantoms were scanned 10 times (each scan was
      analyzed once) with both software versions using all three scanning modes (slow,
      medium, and fast) for a total of 60 scans and analyses. For the intermachine
      comparison, the same phantoms were scanned three times (each scan was analyzed
      once) with a second machine from the same manufacturer using all three scanning
      modes and version 1.35 only. Percentage of fat was the variable of interest.
      RESULTS: For version 1.33, fat was 9.9 +/- 0.4%, 10.0 +/- 0.5%, and 11.0 +/- 0.5%
      (mean +/- SD) for the lean-tissue phantom and 50.8 +/- 0.3%, 50.9 +/- 0.5%, and
      51.1 +/- 0.6% for the fat-tissue phantom using the slow, medium, and fast
      scanning modes, respectively. For version 1.35, the respective fat values were
      9.8 +/- 0.7%, 9.9 +/- 0.4%, and 10.3 +/- 0.7%, and 50.6 +/- 0.5%, 50.9 +/- 0.6%,
      and 50.8 +/- 0.8%, respectively. For the lean-tissue phantom, the estimation of
      percentage of fat was significantly (p < 0.05) affected by scanning mode but not
      by software version. For the fat-tissue phantom, the estimation of percentage of
      fat was not affected by either scanning mode or software version. The use of
      version 1.35 did not effect intermachine variability. DISCUSSION: Versions 1.33
      and 1.35 of the Lunar body composition software appear to be comparable. Soft
      tissue phantoms, such as the ones described in this paper, may be useful in
      monitoring the reproducibility of body composition analyses within and between
      DXA machines, particularly in longitudinal studies.

PMID- 11323451
TI  - Radiology: future challenges.

PMID- 11323452
TI  - Three-dimensional fetal MR imaging: will it fulfill its promise?

PMID- 11323453
TI  - Molecular imaging.
AB  - The term molecular imaging can be broadly defined as the in vivo characterization
      and measurement of biologic processes at the cellular and molecular level. In
      contradistinction to "classical" diagnostic imaging, it sets forth to probe the
      molecular abnormalities that are the basis of disease rather than to image the
      end effects of these molecular alterations. While the underlying biology
      represents a new arena for many radiologists, concomitant efforts such as
      development of novel agents, signal amplification strategies, and imaging
      technologies clearly dovetail with prior research efforts of our specialty.
      Radiologists will play a leading role in directing developments of this embryonic
      but burgeoning field. This article presents some recent developments in molecular
      sciences and medicine and shows how imaging can be used, at least experimentally,
      to assess specific molecular targets. In the future, specific imaging of such
      targets will allow earlier detection and characterization of disease, earlier and
      direct molecular assessment of treatment effects, and a more fundamental
      understanding of the disease process.

PMID- 11323454
TI  - Dental CT imaging: a look at the jaw.
AB  - The jaw comprises two complex bony structures: the mandible and maxilla. Their
      curved or archlike configuration makes radiographic imaging difficult.
      Furthermore, the superimposition of dense teeth and roots may obscure underlying
      tissues, and streak artifacts from dental restorations often degrade computed
      tomographic (CT) images. Recently, dental CT reformatting programs that use thin
      transverse images of the jaw to reformat multiple panoramic and cross-sectional
      views were developed. Since images are reformatted, streak artifacts that degrade
      bone visualization at direct coronal CT are projected over the crowns of the
      teeth, permitting optimal viewing of bone. As a result, these programs have been
      successfully used to evaluate implants, cysts, tumors, and surgical procedures.
      They have created not only a new modality for viewing the jaw but also a new
      partnership between dentists and radiologists. Questions that cannot be answered
      in the dentist's office with conventional radiographs are now answered in
      radiology departments with dental CT scans. The objective of this article is to
      trace, with a series of examples, the effect that this imaging modality has had
      on radiographic evaluation of the jaw and to provide the reader with knowledge
      that should enable him or her to become more involved in imaging of the jaw.

PMID- 11323455
TI  - Spinal vascular malformations: MR angiography after treatment.
AB  - PURPOSE: To evaluate the role of magnetic resonance (MR) angiography in the
      assessment of spinal vascular malformation therapy. MATERIALS AND METHODS: Thirty
      four patients with spinal vascular malformations (30 dural arteriovenous
      fistulas, two perimedullary arteriovenous fistulas, and two intramedullary
      arteriovenous malformations) underwent MR angiography and MR imaging before and
      after endovascular or surgical treatment. RESULTS: MR angiography showed residual
      flow in perimedullary vessels in seven patients with dural fistula after
      embolization with liquid adhesive. In all seven, treatment failure was confirmed
      with arteriography. Long-lasting disappearance of flow in perimedullary vessels
      was demonstrated at MR angiography in 22 patients with dural fistula. MR imaging
      demonstrated normalization of spinal cord volume in 16 of 22 patients and signal
      intensity on T2-weighted images in three patients. Disappearance of cord
      enhancement was observed in five of 21 patients and of perimedullary enhanced
      vessels in six of 13 patients. In one additional patient with dural fistula
      treated with embolization, early posttreatment MR angiography showed
      disappearance of flow in perimedullary vessels, which reappeared at follow-up and
      was consistent with reopening of a small residual fistula. Posttreatment MR
      angiography demonstrated transient reduction of flow in the nidus in two patients
      with intramedullary malformations treated with embolization. Permanent
      disappearance of flow in the perimedullary vessel was seen after endovascular
      treatment in two patients with perimedullary fistula. CONCLUSION: MR angiography
      is more sensitive than MR imaging in depicting residual or recurrent flow in peri
      or intramedullary vessels, which indicates patency of the vascular malformation.

PMID- 11323456
TI  - Increased brain apparent diffusion coefficient in children with neurofibromatosis
      type 1.
AB  - PURPOSE: To describe the changes in brain water diffusibility in five anatomic
      locations in children with neurofibromatosis type 1 (NF 1) compared with these
      changes in control subjects and to describe the water diffusibility changes
      associated with hyperintense basal ganglia lesions in children with NF 1.
      MATERIALS AND METHODS: Twenty highly related pairs of children consisting of one
      child with NF 1 and one unaffected child were examined. Prospective comparisons
      of isotropic apparent diffusion coefficient (ADC) values at five anatomic
      locations were performed, with and without T2-hyperintense lesions included.
      Retrospective analysis of hyperintense globus pallidus lesions in 16 children and
      in the paired control subjects also was performed. RESULTS: Significant increases
      in ADC values were seen in all five anatomic locations in the NF 1 group. The
      greatest increases were seen in the globus pallidus (14%; P =.002) and brachium
      pontis (10.8%; P =.003). With exclusion of hyperintense lesions, significant ADC
      increases were measured in four locations. Significant ADC increases were seen in
      hyperintense globus pallidus lesions in the NF 1 group compared with ADC values
      in the normal-appearing contralateral globus pallidus (4.9%; P =.02) and those in
      the globus pallidus of the paired control subjects (16%; P =.003). CONCLUSION:
      Significant ADC increases were measured both in the hyperintense lesions and in
      the normal-appearing areas of the brain in children with NF 1.

PMID- 11323457
TI  - Implementation of the STOP protocol for Stroke Prevention in Sickle Cell Anemia
      by using duplex power Doppler imaging.
AB  - PURPOSE: To compare the results of the nonduplex ultrasonography (US) Stroke
      Prevention Trial in Sickle Cell Anemia (STOP) with those of transcranial duplex
      power Doppler US by using the STOP protocol and to correlate abnormal
      transcranial Doppler findings with magnetic resonance (MR) imaging and MR
      angiographic findings. MATERIALS AND METHODS: One hundred twenty-five
      asymptomatic patients aged 2-16 years with sickle cell anemia or sickle cell-beta
      thalassemia were examined by using transcranial duplex power Doppler US with a
      2.5-MHz transducer and classified according to STOP criteria. The results were
      compared with those obtained in the nonduplex STOP study. Eight of 10 patients
      with abnormal results, as well as one who had normal results and a subsequent
      stroke, were examined with MR imaging and MR angiography. RESULTS: Ten (8.0%)
      patients were judged to have abnormal findings by using the duplex Doppler US and
      STOP criteria compared with 9.4% of patients in the nonduplex US STOP study. Of
      the eight patients with abnormal transcranial Doppler US results who underwent MR
      imaging and MR angiography, six had abnormal MR imaging findings and all eight
      had abnormal MR angiographic findings. CONCLUSION: The STOP protocol can be
      reproduced by using duplex power Doppler US. Abnormal results with the STOP
      criteria strongly suggest vascular abnormality.

PMID- 11323458
TI  - The naked facet sign.

PMID- 11323459
TI  - Schmorl nodes of the thoracic and lumbar spine: radiographic-pathologic study of
      prevalence, characterization, and correlation with degenerative changes of 1,650
      spinal levels in 100 cadavers.
AB  - PURPOSE: To investigate the frequency and characteristics of Schmorl nodes in an
      elderly population and to correlate these findings with degenerative spinal
      changes. MATERIALS AND METHODS: Cadaveric thoracic and lumbar spines were removed
      at autopsy (mean age at death, 68.2 years; range, 43-93 years). Parasagittal
      sections of approximately 5-mm thickness were obtained and radiographed. At each
      of 3,300 endplates from T1 to L5, the presence of Schmorl nodes was noted.
      Vertebral endplate contour was analyzed, and abnormalities of the discovertebral
      junction were noted. The height of each interspace was measured, and the presence
      or absence of vacuum phenomena and spondylosis was recorded. RESULTS: Schmorl
      nodes were found in 58 specimens and were multiple in 41. Of 3,300 vertebral
      endplates, 225 revealed Schmorl nodes: 88 cranial and 137 caudal. More than 182
      were between T7 and L2. Schmorl nodes correlated with disk space loss (P <.001)
      but not with evidence of advanced disk degeneration: marked disk space loss (P
      =.53), vacuum phenomena (P =.82), or discogenic sclerosis or erosion (P =.35).
      Schmorl nodes were associated with claw (P <.001) but not traction (P =.72)
      osteophytes. Straight (P <.001) and fractured (P <.001) vertebral endplates were
      associated with Schmorl nodes. CONCLUSION: Schmorl nodes are common in the spines
      in an elderly population, with a frequency similar to that in a younger
      population. Schmorl nodes are associated with moderate but not advanced
      degenerative changes. Geometric observations regarding the vertebral endplates
      support the concept that Schmorl nodes are caused by an abnormality of the
      discovertebral junction.

PMID- 11323460
TI  - Normal and acutely torn posterior cruciate ligament of the knee at US evaluation:
      preliminary experience.
AB  - PURPOSE: To determine the ultrasonographic (US) findings of normal and acutely
      torn posterior cruciate ligament (PCL) of the knee and evaluate the usefulness of
      US in the injured PCL. MATERIALS AND METHODS: US images were obtained in 30 knees
      in 15 asymptomatic volunteers as a control group and in 35 patients clinically
      suspected of having an acute PCL injury. Only the distal half of the PCL was
      evaluated. Of the 35 patients, 28 had their PCL status confirmed: 13 had a normal
      PCL at magnetic resonance (MR) imaging plus clinical examination, and 15 had a
      torn PCL at either MR imaging and surgery or MR imaging and clinical follow-up.
      RESULTS: Normal PCLs were homogeneously hypoechoic, with a well-defined posterior
      border. Torn PCLs were heterogeneously hypoechoic (12 [80%] of 15 patients), with
      an indistinct posterior margin (11 [73%] of 15 patients). Torn PCLs were
      significantly thicker (range, 12.0-20.0 mm; mean, 15.6 mm +/- 2.5 [SD]; P <.01),
      as compared with normal PCLs in 13 patients (range, 3.8-5.8 mm; mean, 4.6 mm +/-
      1.0; P <.01) and in the volunteers (range, 3.7-6.2 mm; mean, 4.5 mm +/- 1.2; P
      <.01). CONCLUSION: An acutely torn PCL thickens (>10 mm), loses its sharply
      defined posterior border, and has a heterogeneously hypoechoic appearance. US may
      be useful as a screening examination for patients suspected of having PCL injury
      and for deciding whether to perform more expensive MR imaging or surgical
      intervention.

PMID- 11323461
TI  - Pathogenesis of the Segond fracture: anatomic and MR imaging evidence of an
      iliotibial tract or anterior oblique band avulsion.
AB  - PURPOSE: To demonstrate the normal anatomy of the stabilizing structures of the
      lateral aspect of the knee and to investigate pathogenesis of the Segond
      fracture, with emphasis on the iliotibial tract (ITT) and anterior oblique band
      (AOB) of the fibular collateral ligament. MATERIALS AND METHODS: Dissection of
      the region of the AOB, ITT, and lateral capsular ligament was performed in three
      cadaveric knees, with placement of gadopentetate dimeglumine-filled tubes along
      their course and tibial insertions. These knees, in addition to three
      nondissected knees, were studied with magnetic resonance (MR) imaging by using
      standard and specialized oblique planes. Specimen sectioning provided anatomic
      correlation. Retrospective review of radiographs and MR images in 17 patients
      with acute Segond fractures was performed, and the relationship between the
      fragment and the demonstrated lateral supporting structures of the knee was
      noted. RESULTS: Anatomic dissection and MR imaging of the cadaveric knees
      demonstrated a broad tibial insertion of the ITT, with fibers extending posterior
      to the Gerdy tubercle. A firm band of tissue, the AOB, extended from the fibular
      collateral ligament to the midportion of the lateral tibia, the typical site of a
      Segond fracture. The lateral capsular ligament proved to be a mere thickening of
      the capsule, inserting at the lateral tibia. Clinical analysis of acute Segond
      fractures confirmed the frequent attachment of the ITT and AOB to the avulsed
      fragment. CONCLUSION: Anatomic and clinical findings suggest that fibers of the
      ITT and AOB are important factors in the pathogenesis of the Segond fracture.

PMID- 11323462
TI  - Real-time US versus CT determination of pubic arch interference for
      brachytherapy.
AB  - PURPOSE: Part 1, to determine whether transrectal ultrasonography (US) enables
      accurate determination of pubic arch interference (PAI) for prostate
      brachytherapy (PBT); part 2, to compare the accuracy of transrectal US with that
      of computed tomography (CT) for PAI determination; and part 3, to determine the
      cost savings of PAI determination with transrectal US versus that with CT.
      MATERIALS AND METHODS: Part 1: The pubic arch was identified intraoperatively
      with transrectal US and compared with attempted needle passage (14 patients).
      Part 2: Planning CT with the patient supine was compared with planning
      transrectal US with patients in the dorsal lithotomy position (nine patients).
      Part 3: Cost savings were calculated for PAI determination with transrectal US
      versus that with CT (32 patients per group). RESULTS: Part 1: Transrectal US
      accurately showed the pubic arch relative to the prostate. Part 2: CT resulted in
      PAI overestimation by 11.8 mm. Part 3: Cost savings with transrectal US were
      $1,465 per patient. CONCLUSION: Transrectal US PAI determination is easily
      performed, intraoperatively useful, and accurate. CT can result in PAI
      overestimation. Reducing direct CT costs and the indirect costs of unnecessary
      hormonal therapy for false-positive PAI will reduce expense and improve patient
      care. Transrectal US should replace CT for PAI determination.

PMID- 11323463
TI  - T2 mapping of rat patellar cartilage.
AB  - PURPOSE: To investigate the usefulness of magnetic resonance (MR) T2 mapping in
      characterizing the evolution of cartilage matrix content and thickness during the
      maturation and aging process. MATERIALS AND METHODS: Patellae from four groups of
      rats aged 4 weeks, 8 weeks, 4 months, and more than 6 months ("old rats") were
      studied ex vivo with an 8.5-T microimager. T2 values were calculated on
      transverse rat patellar sections and displayed with a color scale (the T2 map) on
      a pixel-by-pixel basis. Biochemical and histologic studies were performed to
      evaluate the influence of proteoglycans and collagen contents on T2 values of the
      patellar cartilage. RESULTS: On the T2 map, the maturation process until 10 weeks
      was characterized by a decrease in T2 values and in cartilage thickness. The
      biochemical data revealed a global decrease in proteoglycans and a progressive
      global increase in collagen content, whereas the histologic study revealed subtle
      zonal variation in matrix constituents with depth. As aging progressed, the T2
      values were low, without important variations, whereas the global cartilage
      thickness decreased. The cartilage matrix became globally more fibrotic,
      especially in the deepest zone. Biochemical analysis revealed that collagen
      content was more determinant of MR signal intensity than was proteoglycans
      content during maturation and aging. CONCLUSION: T2 mapping allows
      characterization of variations in cartilage matrix constituents and thickness.

PMID- 11323464
TI  - Atherosclerotic plaques: classification and characterization with T2-weighted
      high-spatial-resolution MR imaging-- an in vitro study.
AB  - PURPOSE: To evaluate if T2-weighted high-spatial-resolution magnetic resonance
      (MR) imaging (117 microm per pixel) can help accurate classification of
      atherosclerotic plaques. MATERIALS AND METHODS: Thirty human arteries and 11
      carotid endarterectomy specimens from 31 patients underwent T2-weighted MR
      imaging (2-T magnet; repetition time, 2,000 msec; echo time, 50 msec) at room
      temperature. After imaging, Bouin fixative was used to fix 26 arteries, and the
      other 15 arteries were fixed by means of freezing. Specimens were stained with
      hematoxylin-eosin and safranin or Sudan lipid stain. MR images and histologic
      slices were classified independently by two radiologists and a pathologist,
      respectively, on the basis of the American Heart Association classification.
      RESULTS: Results with MR imaging were the following: type I-II plaques,
      sensitivity of 67% and specificity of 100%; type IV-Va plaques, sensitivity of
      74% and specificity of 85%; type Vb plaques, sensitivity of 90% and specificity
      of 100%; type Vc plaques, sensitivity of 80% and specificity of 90%. No type III
      plaque was diagnosed in the study. The overall kappa value was 0.68. CONCLUSION:
      High-spatial-resolution MR imaging with T2 weighting alone can help accurate
      classification of fibrocalcic plaques (type Vb), but it is subject to limitations
      for the classification and analysis of other types of atherosclerotic plaques.

PMID- 11323465
TI  - Noninvasive localized MR quantification of creatine kinase metabolites in normal
      and infarcted canine myocardium.
AB  - PURPOSE: To develop image-guided spatially localized magnetic resonance (MR)
      spectroscopy to provide a noninvasive quantitative probe of myocardial creatine
      kinase (CK) metabolism, and to use it to determine the extent of changes in CK
      energy metabolism in nonviable infarcted canine myocardium. MATERIALS AND
      METHODS: Water-referenced localized phosphorus and proton MR spectroscopy were
      combined in a single protocol to noninvasively measure phosphocreatine (PCr),
      adenosine triphosphate (ATP), and total of phosphorylated and unphosphorylated
      creatine (CR) concentrations and pH in the myocardium in six normal dogs and six
      dogs with surgically induced myocardial infarction. Unphosphorylated creatine and
      adenosine diphosphate (ADP) levels were calculated. The results were compared
      with biochemical measurements at postmortem biopsy. RESULTS: Significant
      reductions in PCr-to-ATP ratios (1.7 +/- 0.3 [SD] vs 1 +/- 0.4; P <.001), PCr
      (10.3 +/- 2.1 vs 4.3 +/- 2.0 micromol/g wet weight; P <.0001), ATP (6.4 +/- 1.4
      vs 3.7 +/- 1.4 micromol/g wet weight; P <.001), and CR (24.7 +/- 6.1 vs 6.3 +/-
      3.7; P <.0001) were measured noninvasively in infarcted, as compared with normal,
      tissue. Biopsy measurements confirmed infarct-related reductions observed at MR
      spectroscopy, although high-energy phosphate concentrations were lower at biopsy.
      ADP calculated from noninvasive MR spectroscopic measurements was 0.11 +/- 0.07
      micromol/g wet weight in normal myocardium. CONCLUSION: This combined phosphorus
      and proton MR spectroscopic approach provides a near-complete picture of in vivo
      myocardial CK metabolism in normal and diseased heart and a tool for
      noninvasively measuring metabolite reductions associated with the loss of
      viability.

PMID- 11323466
TI  - Renal blood flow changes induced with endothelin-1 and fenoldopam mesylate at
      quantitative Doppler US: initial results in a canine study.
AB  - PURPOSE: To evaluate quantitative Doppler ultrasonography (US) for assessing
      renal blood flow changes induced with endothelin-1 (ET-1) and fenoldopam mesylate
      in conscious dogs. MATERIALS AND METHODS: A blood flow probe was surgically
      implanted around the renal artery in eight adult dogs. Color and power Doppler US
      images were acquired in conscious restrained dogs during intravenous infusion of
      ET-1 and fenoldopam mesylate. Simultaneous with imaging, blood flow through the
      renal artery was measured with the implanted probe. The color level of the images
      within the region representing the kidney was analyzed to derive flow indices.
      These indices were compared with direct-flow measurements. RESULTS: The flow
      indices, color-weighted flow area (CWFA), and percentage of area of color,
      derived from color and power Doppler US images, correlated linearly with direct
      flow. The mean color level of color and power Doppler US images correlated weakly
      with direct flow. Pre- versus postinfusion CWFA decreased with all ET-1 infusions
      (P < or =.032). Infusion of fenoldopam mesylate increased CWFA in all cases (P <
      or =.032). CONCLUSION: Quantitative Doppler US enabled successful measurement of
      the flow changes induced with ET-1 and fenoldopam mesylate. Quantitative Doppler
      US is potentially useful as a noninvasive surrogate endpoint in evaluating the
      action of various therapeutic agents.

PMID- 11323467
TI  - US findings in the scrotum of extreme mountain bikers.
AB  - PURPOSE: To sonographically investigate whether mountain bikers have a higher
      prevalence of scrotal abnormalities compared with that in nonbikers. MATERIALS
      AND METHODS: Eighty-five male mountain bikers (mean age, 25 years; age range, 17
      45 years) and 31 healthy nonbikers (mean age, 24 years; age range, 15-37 years)
      were examined for scrotal findings at ultrasonography (US). Only male subjects
      with a history of extensive off-road biking (> or =2 h/d 6 d/wk; covered
      distance, >5,000 km/y) were assigned to the group of mountain bikers, whereas the
      control group did not engage in bicycling. In addition to clinical evaluation, US
      examination of the scrotum was performed by using a linear-array transducer
      operating at a frequency of 8.0 MHZ: RESULTS: Eighty (94%) mountain bikers had
      abnormal findings at scrotal US. Thirty-nine (46%) had a history of intermittent
      scrotal tenderness or discomfort but no severe scrotal trauma. Abnormal findings
      at US included scrotal calculi in 69 (81%), epididymal cysts in 39 (46%),
      epididymal calcifications in 34 (40%), testicular calcifications in 27 (32%),
      hydroceles in 24 (28%), varicoceles in nine (11%), and testicular microlithiasis
      in one (1%). In the control group, abnormal findings were noted in five (16%),
      all of whom had epididymal cysts. The overall difference in the number of scrotal
      abnormalities in bikers compared with the number in nonbikers was significant (P
      <.0001, chi2 test). CONCLUSION: US shows a significantly higher prevalence of
      extratesticular and testicular disorders in these mountain bikers compared with
      nonbikers.

PMID- 11323468
TI  - Local recurrence after radical prostatectomy: correlation of US features with
      prostatic fossa biopsy findings.
AB  - PURPOSE: To evaluate the diagnostic accuracy of transrectal ultrasonography (US)
      in the detection of local recurrence following radical prostatectomy. MATERIALS
      AND METHODS: Ninety-nine patients with biochemical recurrence after radical
      prostatectomy were evaluated at transrectal US and prostatic fossa biopsy.
      Location of suspected recurrence at transrectal US and clinical features, such as
      prostate-specific antigen levels and digital rectal examination findings, were
      correlated with biopsy results. RESULTS: Forty-one (41%) of 99 cases of local
      recurrence were detected. The percentage of sites of lesions identified at
      transrectal US and corresponding positive biopsy rates were as follows: the
      urethrovesical anastomotic area, 56% and 61%; bladder neck, 26% and 54%;
      retrovesical space, 4% and 100%; and more than one site, 14% and 71%. By
      comparing transrectal US and digital rectal examination, the sensitivities were
      76% and 44% (P =.007), while specificities were 67% and 91% (P =.004),
      respectively. An increased positive biopsy rate with increasing prostate-specific
      antigen levels was noted (P =.04). CONCLUSION: Transrectal US is more sensitive
      but less specific than digital rectal examination in the detection of local
      recurrence. Biopsy findings in more than half of the suspected lesions at the
      urethrovesical anastomotic area and bladder neck were positive. Lesions in the
      retrovesical space, although less frequently encountered, had a high likelihood
      of representing cancer recurrence.

PMID- 11323470
TI  - Case 34: renal lymphangiectasia.

PMID- 11323471
TI  - Hepatocellular carcinoma and dysplastic nodules in patients with cirrhosis:
      prospective diagnosis with MR imaging and explantation correlation.
AB  - PURPOSE: To determine the sensitivity and specificity of magnetic resonance (MR)
      imaging for detection of hepatocellular carcinoma (HCC) and dysplastic nodules
      (DNs) by using explantation correlation in patients with cirrhosis and no known
      HCC. MATERIALS AND METHODS: Seventy-one patients without a known history of HCC
      who underwent MR imaging and subsequent transplantation within 90 days were
      examined. Breath-hold turbo short inversion time inversion-recovery and/or T2
      weighted turbo spin-echo MR images were obtained. Dynamic two- or three
      dimensional gadolinium-enhanced gradient-echo MR images were obtained in the
      hepatic arterial, portal venous, and equilibrium phases. Prospective MR image
      interpretations were compared directly with explanted liver pathologic results.
      RESULTS: Eleven (15%) of 71 patients had hepatic malignancies; MR imaging enabled
      diagnosis of tumor in six (54%) of 11 patients. On a lesion-by-lesion basis, MR
      imaging depicted 11 of 20 hepatic neoplasms, for an overall sensitivity of 55%.
      MR imaging depicted four (80%) of five lesions larger than 2 cm, six (50%) of 12
      lesions 1-2 cm, and one (33%) of three lesions smaller than 1 cm. MR imaging
      depicted only nine (15%) of 59 DNS: The specificities of MR imaging for detection
      of HCC and DNs on a per patient basis were 60 (86%) of 70 patients and 53 (85%)
      of 62 patients, respectively. CONCLUSION: MR imaging is insensitive for the
      diagnosis of small (<2-cm) HCCs and DNS:

PMID- 11323472
TI  - Liver lesion conspicuity: T2-weighted breath-hold fast spin-echo MR imaging
      before and after gadolinium enhancement--initial experience.
AB  - PURPOSE: To evaluate the effect of a gadolinium chelate on T2-weighted breath
      hold fast spin-echo magnetic resonance images of focal hepatic lesions. MATERIALS
      AND METHODS: In 21 patients with focal hepatic lesions, identical T2-weighted
      breath-hold fast spin-echo images were obtained before and after gadolinium
      enhancement and were compared regarding lesion-to-liver contrast-to-noise ratio,
      signal-to-noise ratio, lesion conspicuity, and vascular pulsation artifact. Image
      review was performed independently, in random order, by two experienced
      radiologists. RESULTS: For solid lesions, the lesion-to-liver contrast-to-noise
      ratio on enhanced images was significantly higher (P <.05) than that on
      nonenhanced images. For nonsolid lesions, however, there was no significant
      difference (P =.07). For both readers, lesion conspicuity for solid lesions on
      enhanced images was significantly higher than on nonenhanced images (P <.05).
      Severity of vascular pulsation artifact was not significantly different.
      CONCLUSION: Solid-lesion contrast on T2-weighted breath-hold fast spin-echo
      images improves after administration of a gadolinium chelate. These images should
      be obtained after, rather than before, gadolinium enhancement.

PMID- 11323473
TI  - CT colonography: single- versus multi-detector row imaging.
AB  - PURPOSE: To compare respiratory artifacts, colonic distention, and polyp
      detection at computed tomographic (CT) colonography by using single- and multi
      detector row helical CT systems. MATERIALS AND METHODS: A total of 237
      consecutive patients received subcutaneously administered glucagon and underwent
      prone and supine CT colonography with single-detector row CT (n = 77) and multi
      detector row CT (n = 160), followed by colonoscopy. Examination results were
      graded for colonic distention, respiratory artifacts, and polyp depiction by two
      radiologists working independently. RESULTS: Suboptimal colonic distention was
      significantly more common with single-detector row CT and was present in at least
      one segment in 52% (40 of 77 patients) of examinations versus only 19% (30 of 160
      patients) with multi-detector row CT (P <.001). Mild respiratory artifacts were
      present in 61% (47 of 77 patients) of single-detector row CT examinations versus
      only 16% (26 of 160 patients) of multi-detector row CT examinations (P <.001).
      Depiction of polyps larger than 10 mm was 89% (eight of nine polyps) for single
      detector row CT and 80% (eight of 10 polyps) for multi-detector row CT (P >.05).
      CONCLUSION: CT colonography performed with multi-detector row CT significantly
      improved the demonstration of colonic distention and depicted fewer respiratory
      artifacts compared with single-detector row CT. No significant differences in the
      depiction of polyps larger than 10 mm were demonstrated between single- and multi
      detector row CT for a small number of polyps. Studies with a larger prevalence of
      clinically important polyps are needed for further evaluation of differences in
      polyp detection.

PMID- 11323474
TI  - Providing professional mammography services: financial analysis.
AB  - PURPOSE: To perform a financial analysis of mammography services to determine
      whether the key underlying economic drivers of this service are aligned with the
      public's expectations. MATERIALS AND METHODS: The financial status of mammography
      services at seven university-based programs was assessed by using an extensive
      financial survey encompassing revenue, direct and indirect costs, and volume data
      for 1997 and 1998. At one of the institutions, an activity-based costing analysis
      was performed by procedure type: screening mammography, diagnostic mammography,
      breast ultrasonography, interventional procedures, and review of outside
      mammograms. RESULTS: All seven institutions incurred losses in the professional
      component of mammography services. The underlying financial problem was a
      negative contribution margin (total mammography revenues minus direct expenses).
      The driver of the financial loss was the volume of diagnostic mammograms, which
      generated a loss per procedure. Diagnostic mammogram volume drove the mammography
      full-time equivalent count (P =.039) and was highly and negatively correlated
      with contribution margin (P <.001). CONCLUSION: The reimbursement rate for
      mammography procedures, especially diagnostic mammography, needs to be increased
      to reflect the current reality of the resources necessary to maintain the
      accessibility and accuracy of this evolving mix of clinical services.

PMID- 11323475
TI  - Short-term follow-up results in 795 nonpalpable probably benign lesions detected
      at screening mammography.
AB  - PURPOSE: To evaluate short-term follow-up of nonpalpable probably benign lesions
      in a 2-year mammographic screening. MATERIALS AND METHODS: Of 13,790 women aged
      45-65 years who underwent first-round screening, 795 (5.8%) underwent short-term
      mammographic follow-up (every 6 months for 2 years) of nonpalpable probably
      benign lesions (eg, masses, focal asymmetric densities, and calcifications)
      previously assessed at an additional imaging evaluation, including
      ultrasonography. When no changes were found at short-term mammographic follow-up,
      women were assigned to the 2-year screening interval. Needle localization and
      surgical biopsy were performed when the lesion progressed (was enlarged or had an
      increased number or size of calcifications or modification of their initial
      characteristics). The effectiveness of this approach was evaluated with
      statistical analysis. RESULTS: Of 795 lesions, 788 (99%) remained stable, and
      seven (1%) had changes prompting surgical biopsy. Two cancers (0.3%), one
      microinvasive intraductal carcinoma and one 7-mm invasive ductal carcinoma
      without positive nodes, were found. Four of the five benign histologic results
      were probably benign calcifications with progression at short-term follow-up. The
      sensitivity, specificity, accuracy, and positive and negative predictive values
      were 100%, 99%, 99%, 29%, and 100%, respectively. CONCLUSION: The benign nature
      of most nonpalpable probably benign lesions can be typified with short-term
      mammographic follow-up. This approach permitted identification of a few low-stage
      carcinomas, but progression in the probably benign calcifications was usually
      unrelated to malignancy.

PMID- 11323476
TI  - Update of breast MR imaging architectural interpretation model.
AB  - PURPOSE: To (a) validate a breast magnetic resonance (MR) interpretation model,
      (b) expand the tree-shaped prediction model to increase specificity without
      decreasing sensitivity, and (c) reevaluate the model's diagnostic performance.
      MATERIALS AND METHODS: Two hundred sixty-two new patients with palpable or
      mammographic abnormalities underwent MR imaging, and pathologic evaluation was
      performed. They were entered prospectively into the model, which yielded 454
      patients in the construction (training) and validation (test) phases. Predictive
      values for previously published terminal nodes or branch points of the model were
      compared between the training and test data sets. Ductal enhancement morphology,
      regional enhancement micronodularity, regional enhancement degree, and focal mass
      T2 signal intensity were evaluated for model expansion. Diagnostic performance
      characteristics of the model were recalculated. RESULTS: For previously published
      nodes, absence of a lesion visible at MR imaging, smooth masses, lobulated masses
      with nonenhancing internal septations, and lobulated masses with minimal or no
      enhancement had negative predictive values (NPVs) for malignancy similar in both
      data sets (96% vs 99%, 100% vs 93%, 100% vs 98%, and 100% vs 100%). Irregular
      masses with internal septations (100% vs 0%) and spiculated masses with no or
      minimal enhancement (100% vs 50%) did not. Nonseptated enhancing lobulated masses
      with low T2 signal intensity were added as a benign terminal node (NPV, 100%).
      Mild regional enhancement (NPV, 92%) was added but not considered a terminal
      node. Sensitivity, specificity, NPV, positive predictive value, and accuracy of
      the expanded model were 96%, 80%, 96%, 78%, and 87%, respectively. CONCLUSION:
      Additional investigation yielded a slightly modified model, but the diagnostic
      performance characteristics remain high, similar to those originally published.

PMID- 11323477
TI  - Displacement of microcalcifications during stereotactic 11-gauge directional
      vacuum-assisted biopsy with marking clip placement: case report.
AB  - A 53-year-old woman with right breast microcalcifications of intermediate concern
      underwent stereotactic directional vacuum-assisted biopsy with marking clip
      placement. Postbiopsy mammograms showed displacement of a few of the targeted
      microcalcifications adjacent to misplaced marker clips. Mammography following
      stereotactic breast biopsy is important to document the location and number of
      residual calcifications and to determine the adequacy and location of clip
      placement.

PMID- 11323478
TI  - Deep venous thrombosis with suspected pulmonary embolism: detection with combined
      CT venography and pulmonary angiography.
AB  - PURPOSE: To determine the frequency and location of deep venous thrombosis at
      computed tomographic (CT) venography after CT pulmonary angiography in a large
      series of patients clinically suspected of having pulmonary embolism and to
      compare the accuracy of CT venography with lower-extremity venous sonography.
      MATERIALS AND METHODS: Venous phase images were acquired from the diaphragm to
      the upper calves after completion of CT pulmonary angiography in 650 patients
      (373 women, 277 men; age range, 18-99 years; mean age, 63 years) to determine the
      presence and location of deep venous thrombosis. Results of CT venography were
      compared with those of bilateral lower-extremity venous sonography in 308
      patients. RESULTS: A total of 116 patients had pulmonary embolism and/or deep
      venous thrombosis, including 27 patients with pulmonary embolism alone, 31
      patients with deep venous thrombosis alone, and 58 patients with both. Among 89
      patients with deep venous thrombosis, thrombosis was bilateral in 26, involved
      the abdominal or pelvic veins in 11, and was isolated to the abdominal or pelvic
      veins in four. In patients in whom sonographic correlation was available, CT
      venography had a sensitivity of 97% and a specificity of 100% for femoropopliteal
      deep venous thrombosis. CONCLUSION: Combined CT venography and pulmonary
      angiography can accurately depict the femoropopliteal deep veins, permitting
      concurrent testing for venous thrombosis and pulmonary embolism. CT venography
      also defines pelvic or abdominal thrombus, which was seen in 17% of patients with
      deep venous thrombosis.

PMID- 11323479
TI  - Frequency and CT findings of recurrent disease after lung transplantation.
AB  - PURPOSE: To determine the frequency and computed tomographic (CT) findings of
      recurrence of the primary disease after lung transplantation at six North
      American lung transplantation centers. MATERIALS AND METHODS: Medical records of
      1,394 lung transplant recipients were reviewed to identify patients with
      recurrent primary disease. Their CT scans and pathologic specimens were reviewed.
      RESULTS: The frequency of disease recurrence in the six transplantation centers
      was 1% (15 of 1,394 patients), including six previously reported cases.
      Sarcoidosis recurred in nine (35%) of 26 transplants and was the most common
      disease to recur. Three (33%) of nine patients with recurrent sarcoidosis had
      correlative findings at CT. When present, CT findings were usually different at
      recurrence compared with pretransplantation CT findings. CONCLUSION: A relatively
      small percentage of patients are at risk for recurrence of primary disease
      following lung transplantation. Sarcoidosis is the most common disease to recur.

PMID- 11323480
TI  - Percutaneous image-guided cutting-needle biopsy of the pleura in the presence of
      a suspected malignant effusion.
AB  - PURPOSE: To evaluate the diagnostic accuracy of percutaneous image-guided cutting
      needle biopsy of pleural thickening in the presence of a suspected malignant
      pleural effusion. MATERIALS AND METHODS: Thirty-three adult patients with diffuse
      or focal pleural thickening (median, 1.0 cm; range, 0.2-6.0 cm), pleural
      effusion, and suspected pleural malignancy underwent percutaneous image-guided
      cutting-needle biopsy. Biopsy guidance was performed with computed tomography in
      24 patients and ultrasonography in nine patients. A final diagnosis of benign or
      malignant disease was established with radiologic and clinical follow-up findings
      and with other histologic or cytologic findings, when available. RESULTS: A
      correct histologic diagnosis of malignant disease was made in 21 of 24 patients
      (sensitivity, 88%; specificity, 100%), including 13 of 14 patients with
      mesothelioma (sensitivity, 93%). A correct histologic diagnosis of benign pleural
      disease was made in nine patients. Positive and negative predictive values for
      malignant disease were 100% and 75%, respectively. The overall accuracy was 91%.
      Complications comprised a chest wall hematoma in one patient. CONCLUSION: Image
      guided percutaneous cutting-needle biopsy of pleural thickening in the presence
      of a pleural effusion is a safe procedure, with an overall accuracy of 91% in the
      diagnosis of malignancy.

PMID- 11323481
TI  - Benefits and safety of CT fluoroscopy in interventional radiologic procedures.
AB  - PURPOSE: To determine the benefits and safety of computed tomographic (CT)
      fluoroscopy when compared with conventional CT for the guidance of interventional
      radiologic procedures. MATERIALS AND METHODS: Data on 203 consecutive
      percutaneous interventional procedures performed with use of CT fluoroscopic
      guidance and 99 consecutive procedures with conventional CT guidance were
      obtained from a questionnaire completed by the radiologists and CT technologists
      who performed the procedures. The questionnaire specifically addressed radiation
      dose measurements to patients and personnel, total procedure time, total CT
      fluoroscopy time, mode of CT fluoroscopic guidance (continuous versus
      intermittent), success of procedure, major complications, type of procedure
      (biopsy, aspiration, or drainage), site of procedure, and level of operator
      experience. RESULTS: The median calculated patient absorbed dose per procedure
      and the median procedure time with CT fluoroscopy were 94% less and 32% less,
      respectively, than those measurements with conventional CT scanning (P <.05). An
      intermittent mode of image acquisition was used in 97% of the 203 cases. This
      resulted in personnel radiation dosimetric readings below measurable levels in
      all cases. CONCLUSION: As implemented at the authors' institution, use of CT
      fluoroscopy for the guidance of interventional radiologic procedures markedly
      decreased patient radiation dose and total procedure time compared with use of
      conventional CT guidance.

PMID- 11323482
TI  - Isolated pelvic deep venous thrombosis: relative frequency as detected with MR
      imaging.
AB  - PURPOSE: To determine the relative frequency of deep venous thrombosis (DVT)
      isolated to the pelvic veins, as demonstrated with magnetic resonance (MR)
      imaging. MATERIALS AND METHODS: The reports of 769 MR examinations performed from
      June 1993 through December 1999 in patients with suspected DVT were reviewed
      retrospectively. MR venography was performed by using a two-dimensional gradient
      recalled-echo sequence (typically repetition time, 34 msec; echo time, 13 msec;
      flip angle, 60 degrees ). The presence of DVT was categorized by location in the
      pelvis, thigh, or calf. RESULTS: DVT was identified in 167 (21.7%) of the 769 MR
      examinations. Thirty-four (20.4%) of the 167 studies demonstrated DVT isolated to
      the pelvic veins. CONCLUSION: The relative frequency of isolated pelvic DVT
      detected with MR venography was higher than that reported in prior studies with
      ultrasonography (US) or ascending venography. MR venography should be performed
      in patients with suspected pelvic DVT or when clinical suspicion persists despite
      a negative US study.

PMID- 11323483
TI  - MR imaging-guided stent placement in iliac arterial stenoses: a feasibility
      study.
AB  - PURPOSE: To assess the feasibility of magnetic resonance (MR) imaging-guided
      stent placement in iliac arterial stenoses. MATERIALS AND METHODS: Thirteen
      patients with 14 iliac arterial stenoses were examined prospectively. Angioplasty
      was performed through a femoral sheath by using a conventional 1.5-T MR imaging
      system. Stents and catheters were visualized on the basis of their artifacts.
      Nitinol stents were placed with gradient-echo MR imaging guidance. Angioplasty
      balloons were inflated with gadolinium-based contrast material. Results were
      evaluated clinically and with both digital subtraction angiography (DSA) and
      contrast material-enhanced MR angiography. RESULTS: Ten of 13 patients were
      treated with technical success by using MR imaging-guided intervention alone.
      Three patients were treated with additional fluoroscopic guidance, because
      complications (ie, panic attack, subintimal recanalization, and stent
      misplacement) occurred with MR guidance. The quality of the postinterventional
      contrast-enhanced MR angiograms of three of 12 lesions with stents was limited
      owing to stent-induced signal loss of the lumen. The mean stenosis degree after
      stent placement was significantly higher at contrast-enhanced MR angiography than
      at DSA (24.6% vs 6.2%). The mean MR imaging-guided procedure time was 74 minutes.
      CONCLUSION: MR imaging-guided stent placement in iliac arteries is feasible in
      select patients. The presented technique has limitations-that is, long procedure
      times, lack of real-time monitoring, and stent artifacts-that necessitate further
      modifications before it can be recommended for clinical use.

PMID- 11323484
TI  - Biophysical properties of the normal-sized aorta in patients with Marfan
      syndrome: evaluation with MR flow mapping.
AB  - PURPOSE: To investigate the feasibility of magnetic resonance (MR) flow mapping
      in the assessment of aortic biophysical properties in patients with Marfan
      syndrome and to detect differences in biophysical properties in the normal-sized
      aorta distal to the aortic root between these patients and matched control
      subjects. MATERIALS AND METHODS: Seventy-eight patients with Marfan syndrome with
      aortic root dilatation and 23 matched control subjects underwent MR flow mapping
      in four locations in the normal-sized aorta (1, ascending aorta; 2, thoracic
      descending aorta; 3, descending aorta at the level of the diaphragm; and 4,
      abdominal descending aorta). Distensibility at each location and flow wave
      velocity between locations were calculated. RESULTS: Compared with the control
      subjects, patients with Marfan syndrome had decreased aortic distensibility at
      three of the four locations (levels 1, 2, and 4; P <.05) and increased flow wave
      velocity between all locations (P <.05) in the aorta. In patients with Marfan
      syndrome, flow wave velocity was also significantly increased along the entire
      aortic tract beyond the aortic root (from level 1 to level 4). CONCLUSION: MR
      imaging reveals abnormal biophysical properties of the normal-sized aorta in
      patients with Marfan syndrome. Monitoring of these properties is relevant for
      evaluating disease progression and treatment options.

PMID- 11323485
TI  - Mechanical detachable platinum coil: report of the European phase II clinical
      trial in 60 patients.
AB  - PURPOSE: To determine the safety and reliability of the mechanical detachment
      system of a platinum coil (Detach-18) when used for neurovascular embolization.
      MATERIALS AND METHODS: Sixty patients (21 men, 39 women; age range, 26-75 years;
      mean age, 56.2 years) were treated in seven centers. Ease of introduction of the
      coil to the microcatheter, effect of coil passage on the microcatheter shape and
      stability during its delivery, retrievability of the coil before and after the
      transition zone passed beyond the microcatheter, detachment of the coil, and
      effect of coil rotation on the microcatheter stability were evaluated. The
      detachment system itself was evaluated for premature detachment, failure of the
      coil to detach, detachment time, number of turns, visibility of radiopaque
      markers, number of coils deployed per patient, and percentage of vessel occlusion
      obtained. A 0.015-inch-diameter regular coil and a 0.014-inch-diameter soft coil
      were used. RESULTS: A total of 1,061 coils were used; 1,009 were detached. The
      number of coils deployed ranged from four to 104 (mean, 17 coils). The coils
      passed easily through the microcatheter. The detachment maneuver occurred within
      5-25 seconds, with five to 60 turns of the introducing wire. One premature coil
      detachment occurred without clinical sequela; 100% occlusion of the vessel lumen
      was achieved in 53 patients; 80%-90%, in four; and 70%-80%, in two. There were no
      device-related complications. CONCLUSION: The detachment system was safe and
      reliable. This is a useful system for coil embolization in neurovascular
      diseases.

PMID- 11323486
TI  - Comparison of single-shot fast spin-echo and conventional spin-echo sequences for
      MR imaging of the heart: initial experience.
AB  - A conventional T1-weighted spin-echo (SE) magnetic resonance (MR) imaging
      sequence was compared with breath-hold and non-breath-hold half- Fourier single
      shot fast SE MR sequences with black-blood preparation and high spatial
      resolution for imaging of various cardiac diseases. The optimized single-shot
      fast SE sequence provided better or equal image quality in less time. Breath-hold
      and non-breath-hold single-shot fast SE sequences may replace the conventional T1
      weighted SE sequence for first-line cardiac MR imaging.

PMID- 11323487
TI  - Rapid aortic wave velocity measurement with MR imaging.
AB  - The utility of a one-dimensional magnetic resonance (MR) sequence to rapidly and
      accurately measure wave velocity in vivo was evaluated. Studies were conducted in
      the thoracic aortas of 20 healthy subjects of varying age, and the MR method was
      validated in a compliant tube model. Aortic wave velocity ranged from 3.8 to 9.7
      m/sec and demonstrated a positive correlation with subjects' age. Peak blood
      velocity ranged from 47 to 125 cm/sec and exhibited a strong negative correlation
      with subjects' age.

PMID- 11323488
TI  - Colon carcinoma: MR imaging with CO2 enema--pilot study.
AB  - Prior to surgery, seven patients with known colonic tumors underwent breath-hold
      single-shot fast spin-echo magnetic resonance imaging during a CO2 enema. The
      images were evaluated for depiction of tumor, adjacent structures, and the
      remaining colon, and findings were compared with findings at surgery. In all
      seven patients, the tumor was demonstrated, and in four (57%), breach of the
      muscularis propria was correctly predicted.

PMID- 11323489
TI  - The fetus at term: in utero volume-selected proton MR spectroscopy with a breath
      hold technique--a feasibility study.
AB  - In three healthy gravidas at 38 and 39 weeks gestation, fetal MR spectroscopy was
      performed with a breath-hold technique by using the following pulse sequences:
      single voxel point-resolved spectroscopy, or PRESS, for liver and heart studies
      and stimulated-echo acquisition mode, or STEAM, for brain studies. Signal peaks
      of lipid from heart and liver were detected, as were the signal peaks of choline,
      creatine, and N-acetylaspartate from fetal brain. Findings demonstrated the
      feasibility of performing proton MR spectroscopy to assess mobile fetal
      structures.

PMID- 11323490
TI  - Fetus and uteroplacental unit: fast MR imaging with three-dimensional
      reconstruction and volumetry--feasibility study.
AB  - In 22 fetuses, three-dimensional reconstruction was performed on the basis of T2
      weighted magnetic resonance (MR) data sets by using a surface-rendering
      technique. Fetuses and uteroplacental units were segmented manually; volumes were
      calculated automatically. Three-dimensional reconstruction and volumetry of the
      fetus and uteroplacental unit are feasible with MR data sets. MR estimates
      correlated closely with ultrasonographic fetal biometric estimates and birth
      weight.

PMID- 11323491
TI  - Imaging in women with persistent pelvic pain.

PMID- 11323492
TI  - Embolization of an autologous clot.

PMID- 11323493
TI  - Duplex US for the estimation of internal carotid stenosis.

PMID- 11323494
TI  - Radiation dose in fluoroscopically guided dacryocystoplasty.

PMID- 11323497
TI  - Odyssey of an academic surgeon.

PMID- 11323498
TI  - Insulinoma-induced hypoglycemic death in mice is prevented with beta cell
      specific gene therapy.
AB  - OBJECTIVE AND SUMMARY BACKGROUND DATA: Tumor-specific gene therapy can be
      achieved if a tumor-specific promoter can be identified. In this study the
      authors investigated the use of the rat insulin promoter (RIP) for insulinoma
      specific expression of a reporter gene. Insulinoma-specific cytotoxicity using
      the suicide gene thymidine kinase (tk) was studied both in vitro and in vivo.
      RIPtk gene therapy, delivered by a nontoxic, noninflammatory liposomal delivery
      system, was used in an insulinoma ICR/SCID mouse model to prevent hypoglycemic
      death. METHODS: Rat insulin promoter (0.502 kb) was ligated to the reporter gene
      lacZ and ligated to the tk gene. These two genes were transfected into a mouse
      insulinoma (NIT) cell line to ascertain insulinoma-specific expression and
      insulinoma-specific cytotoxicity in vitro. Reverse transcriptase-polymerase chain
      reaction and electrophoretic mobility-shift assays were performed on NIT-1 cell
      RNA and nuclear extract, respectively, to determine the transcription factors
      present and responsible for RIP activation in NIT-1 cells. A mouse insulinoma
      model was created with NIT-1 cells. These mice were treated with the RIPtk gene,
      and both blood sugars and animal viability were monitored. RESULTS: Only NIT-1
      cells stained blue after X-gal staining or had detectable levels of beta
      galactosidase protein. A significant decrease in cell survival was observed in
      NIT-1 cells transfected with RIPtk in vitro. Messenger RNA for both BETA2 and PDX
      1 was found in NIT-1 cells, and a supershift was observed for both BETA2 and PDX
      1. Experimental mice treated with the RIPtk gene, delivered by a liposomal gene
      delivery system, maintained their blood glucose levels, and the animals did not
      die of hypoglycemia. CONCLUSIONS: The data suggest that the RIP is an insulinoma
      specific promoter. An ICR/SCID mouse insulinoma model was used to show that
      insulinoma-specific cytotoxicity can be accomplished by RIP coupled to a suicide
      gene in vivo, preventing hypoglycemic death.

PMID- 11323499
TI  - Coronary artery bypass surgery: are outcomes influenced by demographics or
      ability to pay?
AB  - OBJECTIVE: To examine the relation of financial status and demographics to the
      outcomes of coronary artery bypass surgery (CABG) in the public hospital setting.
      SUMMARY BACKGROUND DATA: Coronary artery bypass surgery is one of the most
      expensive and frequently performed surgical procedures in the United States.
      Considerable controversy surrounds the accessibility to quality cardiac care of
      indigent and minority populations. This study examines the hypothesis that
      demographics rather than access to care and economics influences outcomes in
      CABG. METHODS: A retrospective review of 1,556 charts of patients who underwent
      CABG at Louisiana State University Health Sciences Center-Shreveport, a public
      hospital, during a 10-year period was performed. The parameters analyzed included
      sex, age, race, education, ejection fraction, comorbidities, surgical parameters,
      economics, complications, and cost of care. Comparisons were made between the
      insured and uninsured groups. Univariate statistical analysis was used to assess
      differences between groups. Kaplan-Meier survival curves were also generated.
      RESULTS: Two thirds of the patients were uninsured. The mean age of the uninsured
      patients was significantly lower than that of the insured patients. Ejection
      fractions were comparable. Comorbidities were similar, with a greater percentage
      of tobacco use in the uninsured population. Kaplan-Meier survival curves showed
      that the uninsured group had better overall survival and that the insured group
      manifested an increased rate of late death. CONCLUSIONS: The financially
      challenged population appears to present for treatment earlier in life with
      coronary artery disease. Risk factors between the two groups were similar, except
      that tobacco use appears to be a significant problem in the disadvantaged
      population. The disease severity in both populations appeared to be similar;
      however, the uninsured patients had equivalent early survival with better late
      survival. Access to care in both groups was equal. In the public hospital setting
      for the disease state described, the financially challenged are afforded access
      to the current treatment technology with quality results.

PMID- 11323500
TI  - Interferon regulatory factor expression in human breast cancer.
AB  - OBJECTIVE: To investigate the expression of interferon regulatory factors 1 and 2
      (IRF-1 and IRF-2) in human breast cancer. SUMMARY BACKGROUND DATA: Interferon
      regulatory factors 1 and 2 are transcription factors in the interferon gamma
      signal transduction pathway. IRF-1 acts as the effector arm of the interferon
      gamma response; IRF-2 binds to the same DNA consensus sequence and opposes IRF-1
      activity. Previous work in the authors' laboratory has shown the tumor suppressor
      activity of IRF-1 expression and the oncogenic effect of IRF-2 in human and
      murine tumor models, including human breast cancer cell lines. The authors'
      hypothesis is that this pathway is involved in human tumor development, and
      alterations in the expression of IRF-1 and IRF-2 may occur in breast cancer
      tissue compared with normal breast tissue, and between more and less
      differentiated breast cancers. METHODS: Formalin-fixed paraffin-embedded human
      archival tissue specimens were obtained from 33 patients with pure ductal
      carcinoma in situ (DCIS) and 49 women with invasive ductal cancer. Adjacent areas
      of normal breast tissue were assayed in 31 women. These specimens were stained
      with polyclonal IRF-1 and IRF-2 antibodies using an avidin-biotin-peroxidase
      complex technique after epitope retrieval. RESULTS: Most normal breast tissue
      showed expression of IRF-1 and no expression of IRF-2 by immunohistochemistry.
      High-grade DCIS or node-positive invasive ductal cancers were less likely to
      express the tumor suppressor IRF-1 than normal tissue. More strikingly, high
      grade DCIS and invasive ductal cancers were much more likely to express the
      oncogenic IRF-2 protein than was normal tissue. CONCLUSIONS: Expression of IRF-1
      and IRF-2 is altered in human breast cancer compared with normal adjacent tissue.
      The loss of IRF-1 expression is consistent with tumor suppressor loss and the
      development of IRF-2 expression with oncogenic activation. These data support the
      hypothesis that this pathway is involved in human breast oncogenesis, which
      warrants further investigation regarding prognostic and therapeutic implications.

PMID- 11323502
TI  - Pancreatic transplantation and subsequent graft surveillance by pancreatic portal
      enteric anastomosis and temporary venting jejunostomy.
AB  - OBJECTIVE: To evaluate portal-enteric (PE) pancreas and kidney transplantation
      with venting jejunostomy (VJ) for its efficacy, safety, and reproducibility.
      SUMMARY BACKGROUND DATA: Simultaneous pancreas and kidney transplantation for
      patients with long-standing insulin-dependent diabetes mellitus that progresses
      to renal failure has revolutionized their treatment and quality of life. A
      current clinical focus is to refine the technical aspects of this procedure.
      Simultaneous pancreas and kidney transplantation with PE anastomosis with VJ
      appears to offer several advantages over bladder drainage. VJ allows initial
      decompression of the enteric anastomosis, monitoring of pancreatic function by
      ostomy amylase, and simple access for endoscopic evaluation and biopsy of the
      allograft. METHODS: Simultaneous pancreas and kidney transplantation with VJ was
      performed in 21 patients from December 1996 to October 2000 at Willis
      Knighton/LSU Regional Transplant Center. All patients had long-standing insulin
      dependent diabetes mellitus and subsequent renal failure. They were evaluated at
      the time of surgery by a multidisciplinary transplant team and monitored for
      numerous factors, including length of hospital stay, immunosuppressive regimen,
      and ischemia times. All patients had intermittent visual and biochemical
      evaluation of pancreatic secretions monitored by means of the VJ. RESULTS: Of the
      21 patients, 10 were women and 11 were men. Four patients were black and 17 were
      white. The mean age at transplantation was 38 years; average human leukocyte
      antigen (HLA) match was one; and average cold ischemia time was 12 hours. The
      median hospital stay was 16 days. Four episodes of postoperative bleeding
      requiring exploration occurred in four patients. Postoperative wound infections
      developed in four patients. There were 12 episodes of rejection in nine patients.
      All patients with suspected acute pancreatic rejection underwent endoscopy by
      means of the VJ and duodenal biopsy for evaluation. Two patients lost pancreatic
      function subsequent to kidney failure, one secondary to noncompliance and the
      other as a result of hemolytic-uremic syndrome. Patient, kidney, and pancreatic
      survival rates were 100%, 90%, and 90%, respectively. The mean follow-up period
      was 25 (range 2-48) months. CONCLUSION: The authors believe that PE pancreatic
      drainage with VJ is a more physiologic method to perform pancreatic
      transplantation than bladder drainage. PE drainage allows rapid diagnosis of
      acute rejection and anastomotic leak and provides a simple way to monitor ostomy
      amylase and transplant duodenal bleeding. This technique is safe and has minimal
      associated complications.

PMID- 11323501
TI  - Molecular biomarkers for breast cancer prognosis: coexpression of c-erbB-2 and
      p53.
AB  - OBJECTIVE: To assess the prognostic significance of molecular biomarkers,
      particularly c-erbB-2 and p53, through study of prospective clinical data and
      archival breast cancer tissues for women accrued to the Alabama Breast Cancer
      Project. SUMMARY BACKGROUND DATA: Defining molecular abnormalities in breast
      cancer is an important strategy for early detection, assessment of prognosis, and
      treatment selection. Evidence is strong that selective biomarkers, including c
      erbB-2 and p53, have prognostic significance in breast cancer. Few studies have
      analyzed the prognostic significance of coexpression of biomarkers. METHODS:
      Study patients were those accrued to the Alabama Breast Cancer Project (1975
      1978) who had archival breast cancer tissues available for analysis. Criteria for
      entrance into the Alabama Breast Cancer Project were T1-3 breast cancer with M0
      status. Age, nodal status, and histologic grade were also documented. Patients
      were randomized to radical versus modified radical mastectomy, and node-positive
      patients were also randomized to adjuvant chemotherapy (cyclophosphamide,
      methotrexate, and 5-fluorouracil [CMF]) versus melphalan. Archival breast cancer
      tissues were studied for c-erbB-2, TGF-alpha, p53, cathepsin D, bcl-2, and
      estrogen and progesterone receptor expression using immunohistochemistry.
      Survival curves were developed using the Kaplan-Meier method. Univariate analysis
      was performed using the log-rank test, multivariate analysis using a rank
      regression model. RESULTS: Three hundred eleven patients were accrued to the
      Alabama Breast Cancer Project, and paraffin-embedded breast cancer tissues for 90
      patients were available for immunohistochemical analysis of molecular biomarkers.
      Univariate analysis showed nodal status, c-erbB-2 expression, and p53 expression
      to have prognostic significance. Coexpression of c-erbB-2 and p53 was also found
      to have prognostic significance by the log-rank test. Multivariate analysis
      showed T stage, nodal status, c-erbB-2 expression, and p53 expression to have
      independent prognostic significance. CONCLUSIONS: These data suggest that c-erbB
      2 and p53 expression in breast cancer have prognostic significance. After median
      follow-up of 16 years, coexpression of c-erbB-2 and p53 may have more prognostic
      significance than traditional prognostic factors such as T stage and nodal
      status. Prospective study of large numbers of patients with breast cancer is
      encouraged to validate these findings.

PMID- 11323503
TI  - Are concerns over right laparoscopic donor nephrectomy unwarranted?
AB  - OBJECTIVE: To examine the ability of several large, experienced transplantation
      centers to perform right-sided laparoscopic donor nephrectomy safely with
      equivalent long-term renal allograft function. SUMMARY BACKGROUND DATA: Early
      reports noted a higher incidence of renal vein thrombosis and eventual graft
      loss. However, exclusion of right-sided donors would deprive a significant
      proportion of donors a laparoscopically harvested graft. METHODS: A retrospective
      review was performed among 97 patients from seven centers performing right-sided
      laparoscopic donor nephrectomy. Surgical and postoperative demographic factors
      were evaluated. Complications were identified and long-term renal allograft
      function was compared with historical left-sided laparoscopic donor nephrectomy
      cohorts. RESULTS: Right laparoscopic donor nephrectomy was performed for varying
      reasons, including multiple left renal arteries or veins, smaller right kidney,
      or cystic right renal mass. Mean surgical time was 235.0 +/- 66.7 minutes, with a
      mean blood loss of 139 +/- 165.8 mL. Conversion was required in three patients
      secondary to bleeding or anatomical anomalies. Mean warm ischemic time was
      limited at 238 +/- 112 seconds. Return to diet was achieved on average after 7.5
      +/- 2.3 hours, with mean discharge at 54.6 +/- 22.8 hours. Two grafts were lost
      during the early experience of these centers to renal vein thrombosis. Both
      surgical and postoperative complications were limited, with few long-term adverse
      effects. Mean serum creatinine levels were higher than open and left laparoscopic
      donor nephrectomy on postoperative day 1, but at all remaining intervals the
      right laparoscopic donors had equivalent creatinine values. CONCLUSIONS: These
      results confirm that right laparoscopic donor nephrectomy provides similar
      patient benefits, including early return to diet and discharge. Long-term
      creatinine values were no higher than in traditional open donor or left
      laparoscopic donor cohorts. These results establish that early concerns about
      high thrombosis rates are not supported by a multiinstitutional review of
      laparoscopic right donor nephrectomies.

PMID- 11323504
TI  - Liver transplantation for hepatocellular carcinoma.
AB  - OBJECTIVE: To analyze patient and tumor characteristics that influence patient
      survival to select patients who would most benefit from liver transplantation.
      SUMMARY BACKGROUND DATA: The selection of patients with hepatocellular carcinoma
      (HCC) for liver transplantation remains controversial. METHODS: One hundred
      twelve patients with nonfibrolamellar HCC who underwent a liver transplant from
      1985 to 2000 were reviewed. Survival was calculated using the Kaplan-Meier
      method, with differences in outcome assessed using the log-rank procedure.
      Multivariate analysis was then performed using a Cox regression model. RESULTS:
      Overall patient survival rates were 78%, 63%, and 57% at 1, 3, and 5 years,
      respectively. Patients infected with the hepatitis B virus had a worse 5-year
      survival than those who were not (43% vs. 64%), with most deaths being attributed
      to recurrent hepatitis B. However, patients with hepatitis B virus who underwent
      more recent transplants using antiviral therapy fared as well as those who were
      negative for the virus, showing a 5-year survival rate of 77%. Patients with
      vascular invasion by tumor had a worse 5-year survival than patients without
      vascular invasion (33% vs. 68%). Vascular invasion, tumor size greater than 5 cm,
      and poorly differentiated tumor grade were predictors of tumor recurrence by
      univariate analysis; however, only vascular invasion remained significant on
      multivariate analysis: the rate of tumor recurrence at 5 years was 65% in
      patients with vascular invasion and only 4% for patients without vascular
      invasion. CONCLUSIONS: For well-selected patients with HCC, liver transplantation
      in the current era can achieve equivalent results to transplantation for
      nonmalignant indications. Vascular invasion is an indicator of high risk of tumor
      recurrence but is difficult to detect before transplantation.

PMID- 11323505
TI  - Enteral nutrition prevents remote organ injury and death after a gut ischemic
      insult.
AB  - OBJECTIVE: To determine whether parenteral feeding (IV-TPN) influences the local
      and systemic response to an intestinal insult. SUMMARY BACKGROUND DATA:
      Parenteral feeding increases ICAM-1 expression and attracts neutrophils (PMNs) to
      the intestine compared with enterally fed animals. Because the gut is a priming
      bed for PMNs, the authors hypothesized that IV-TPN may affect organ injury after
      gut ischemia-reperfusion (I/R). METHODS: Mice were randomized to chow, IV-TPN,
      intragastric TPN, or complex enteral diet for 5 days' feeding. In experiment 1,
      162 mice underwent 15 or 30 minutes of gut I/R, and death was recorded at 72
      hours. In experiment 2, 43 mice underwent 15 minutes of gut ischemia and
      permeability was measured by 125I-labeled albumin at 3 hours after reperfusion.
      Lung PMN accumulation was measured by myeloperoxidase assay. In experiment 3,
      albumin leak was tested in the complex enteral diet group (n = 5) and the
      intragastric TPN group (n = 5) after 30 minutes of gut ischemia and 1 hour of
      reperfusion. RESULTS: In experiment 1, enteral feeding significantly reduced the
      death rate compared with IV-TPN after 15 minutes of I/R. After 30 minutes of gut
      ischemia, the IV-TPN and intragastric TPN groups showed a higher death rate than
      the chow and enteral diet groups. In experiment 2, IV-TPN significantly increased
      pulmonary and hepatic 125I albumin leak compared with enteral feeding without
      increasing pulmonary myeloperoxidase levels. In experiment 3, there were no
      differences in 125I albumin leak between the complex enteral diet and
      intragastric TPN groups. CONCLUSION: Enteral feeding reduced the death rate and
      organ permeability after 15 minutes of ischemia. However, prolonged ischemia (30
      minutes) eliminated any benefits of intragastric TPN on survival.

PMID- 11323506
TI  - Hematoma-directed ultrasound-guided breast biopsy.
AB  - OBJECTIVE AND SUMMARY BACKGROUND DATA: The standard technique for removal of
      nonpalpable breast lesions is needle localization breast biopsy. Because
      traumatic hematomas can often be seen with ultrasound, the authors hypothesized
      that iatrogenically induced hematomas could be used to guide the excision of
      nonpalpable lesions using ultrasound. METHODS: Twenty patients with nonpalpable
      breast lesions detected by magnetic resonance imaging only were enrolled in this
      single-institution trial, approved by the institutional review board. A hematoma
      consisting of 2 to 5 mL of the patient's own blood was injected into the breast
      to target the nonpalpable lesion. Intraoperative ultrasound of the hematoma was
      used to direct the excisional biopsy. RESULTS: The average age of women was 53.8
      +/- 10 years. Ninety-five percent of lesions detected by magnetic resonance
      imaging were localized by hematoma injection. All the hematomas used to recognize
      targeted lesions were identified at surgery by ultrasound and removed without
      complication. Eight (40%) of the lesions were malignant, with an average tumor
      size of 12 +/- 6 mm (range 4-25). The remaining 12 lesions (60%) comprised
      papillomas, sclerosing adenosis, radial scar, fibroadenoma, and areas of atypical
      ductal hyperplasia. CONCLUSION: The results of this pilot study show the
      effectiveness of hematoma-directed ultrasound-guided breast biopsy for
      nonpalpable lesions seen by magnetic resonance imaging. This new procedure is
      potentially more comfortable for the patient because no wire or needle is left in
      the breast. It is technically faster and easier because ultrasound is used to
      visualize directly the location of the hematoma at surgery and to confirm lesion
      removal in the operating room by specimen ultrasound. The hematoma can be placed
      several days before biopsy, easing scheduling, and without fear of the migration
      that may occur with needle localization. This method may have ready application
      to mammographically detected lesions.

PMID- 11323507
TI  - Promoting effect of a high-fat/high-protein diet in DMBA-induced ductal
      pancreatic cancer in rats.
AB  - OBJECTIVE: To investigate whether a high-fat/high-protein diet (HFPD) acts as a
      promoter of the natural course of cancer growth in the 7,12
      dimethylbenzanthracene (DMBA)-induced ductal pancreatic cancer model in rats.
      SUMMARY BACKGROUND DATA: DMBA implantation to the rat pancreas induces ductal
      adenocarcinoma. Information regarding the effects of diet and the presence of K
      ras mutation in this model is not available. METHODS: Rats were randomly assigned
      to regular rat chow or a diet with a 30% content in fat and protein (HFPD). The
      presentation of cancer, the histologic spectrum of neoplasia at 1 and 9 months,
      and the prevalence of cancer in relation to diet were assessed. Histologic
      specimens comprising normal ducts, hyperplasia, dysplasia/carcinoma in situ, or
      carcinoma were designated by a pathologist and microdissected. Genomic DNA was
      extracted, and K-ras and H-ras gene mutations were determined by a mutant
      enriched polymerase chain reaction assay and direct sequencing. RESULTS: Rats fed
      HFPD increased their weight significantly compared with controls. DMBA induced
      characteristic stages of neoplasia at the implant site but not elsewhere.
      Macroscopic cancers of the pancreatic head presented regularly with common bile
      duct and gastric outlet obstruction. The prevalence of K-ras mutations was
      proportional to the degree of epithelial abnormality. K-ras mutations were
      significantly more frequent in cancer than in normal and hyperplastic ducts. H
      ras mutations were not found. At 1 month in the HFPD-fed rats, the prevalence of
      cancer (16%) and dysplasia (16%) was not significantly different from the
      prevalence of cancer (29%) and dysplasia (8%) in the chow-fed rats. At 9 months
      the prevalence of cancer in the HFPD-fed rats increased to 29%, whereas that in
      the chow-fed rats decreased to 17%. The combined prevalence of cancer and
      dysplasia at 9 months in the HFPD-fed rats (34%) significantly exceeded that in
      the chow-fed rats. CONCLUSIONS: DMBA induces characteristic stages of neoplasia
      in the evolution of ductal pancreatic cancer in rats. K-ras mutations occur
      progressively in the ladder of oncogenesis, as in human pancreatic neoplasms. The
      addition of a diet with a high fat and protein content acts as a promoter of
      carcinogenesis, possibly by interfering with repair mechanisms and natural
      regression of early lesions.

PMID- 11323508
TI  - High-throughput drug screening of the DPC4 tumor-suppressor pathway in human
      pancreatic cancer cells.
AB  - OBJECTIVE: To screen a library of small chemicals for compounds that activate the
      DPC4 signal transduction pathway in a human pancreatic cancer cell line. SUMMARY
      BACKGROUND DATA: Various tumor-suppressor genes are mutated in all human cancers.
      Specifically, DPC4 (deleted in pancreatic carcinoma, locus 4 or MADH4/SMAD4) is a
      tumor-suppressor gene mutated in approximately 50% of human pancreatic
      adenocarcinomas. DPC4 plays an important role in the well-studied transforming
      growth factor-beta (TGFbeta) signaling pathway. It would be useful to identify
      therapies that augment or restore the downstream functions of this critical
      signal transduction pathway, in hopes that such therapy would have a rational
      role in anticancer therapy. METHODS: Using a commercially available plasmid
      vector with a luciferase reporter gene already incorporated, a DPC4-specific
      reporter construct was genetically engineered. This was done by inserting six
      copies of the palindromic Smad binding element (6SBE), which is a DNA binding
      element specific for DPC4, in front of the minimal promoter in the plasmid. This
      construct was then stably integrated into the genome of a human pancreatic cancer
      cell line (PANC-1) that has wild-type DPC4. Several stably transfected clones
      were tested for basal luciferase expression and inducibility with TGFbeta, which
      is known to activate the DPC4 signal transduction pathway. A single transfected
      clone was chosen for the drug screen based on basal luciferase (reporter)
      expression and TGFbeta inducibility. A systematic screen of the chemical library
      was then performed, using luciferase activity to detect DPC4 activity and
      induction of the signaling pathway. RESULTS: A high-throughput system based on
      this stably integrated reporter system was used to screen a library of 16,320
      random compounds to identify agents that conferred robust augmentation of the
      DPC4 signal transduction pathway. Of the 16,320 compounds screened, 11 were
      associated with a 2- to 5-fold induction of luciferase activity, and one with a
      12-fold activation. The latter compound was shown to be a novel histone
      deacetylase inhibitor and was further characterized. CONCLUSIONS: These results
      confirm the feasibility of a specific high-throughput reporter system to screen a
      large compound library in human cells efficiently. The screening identified
      several compounds capable of augmenting DPC4-specific luciferase reporter
      activity, and a specific mechanism for one compound was identified. The discovery
      of such agents will aid our understanding of complex tumor-suppressive signaling
      pathways and may identify other potential therapeutic targets within this
      critical signaling pathway. In addition, random drug screening provides an
      unbiased method for identifying drugs or lead compounds for potential therapeutic
      use.

PMID- 11323510
TI  - Randomized prospective evaluation of frozen-section analysis for follicular
      neoplasms of the thyroid.
AB  - OBJECTIVE: To evaluate the clinical utility of frozen section in patients with
      follicular neoplasms of the thyroid in a randomized prospective trial. SUMMARY
      BACKGROUND DATA: The finding of a follicular neoplasm on fine-needle aspiration
      prompts many surgeons to perform intraoperative frozen section during thyroid
      lobectomy. However, the focal distribution of key diagnostic features of
      malignancy contributes to a high rate of noninformative frozen sections. METHODS:
      The series comprised 68 consecutive patients with a solitary thyroid nodule in
      whom fine-needle aspiration showed a follicular neoplasm. Patients were excluded
      for bilateral or nodal disease, extrathyroidal extension, or a definitive fine
      needle aspiration diagnosis. Final pathologic findings were compared with frozen
      sections, and cost analyses were performed. RESULTS: Sixty-one patients met the
      inclusion criteria. Twenty-nine were randomized to the frozen-section group and
      32 to the non-frozen-section group. In the non-frozen-section group, one patient
      was excluded when gross examination of the specimen was suggestive of malignancy
      and a directed frozen section was diagnostic of follicular carcinoma. Frozen
      section analysis rendered a definitive diagnosis of malignancy in 1 of 29 (3.4%)
      patients, who then underwent a one-stage total thyroidectomy. In the remaining 28
      patients, frozen section showed a "follicular or Hurthle cell neoplasm."
      Permanent histology demonstrated well-differentiated thyroid cancer in 6 of these
      28 patients (21%). Of the 31 patients in the non-frozen-section group, 3 (10%)
      showed well-differentiated thyroid carcinoma on permanent histology.
      Complications were limited to one transient unilateral vocal cord dysfunction.
      All but one patient had a 1-day hospital stay. There were no significant
      differences between the groups in surgical time or total hospital charges;
      however, the charge per informative frozen section was approximately $12,470.
      CONCLUSIONS: For the vast majority of patients (96.4%) with follicular neoplasms
      of the thyroid, frozen section is neither informative nor cost-effective.

PMID- 11323509
TI  - Outpatient laparoscopic cholecystectomy: patient outcomes after implementation of
      a clinical pathway.
AB  - OBJECTIVE: To determine the success of a clinical pathway for outpatient
      laparoscopic cholecystectomy (LC) in an academic health center, and to assess the
      impact of pathway implementation on same-day discharge rates, safety, patient
      satisfaction, and resource utilization. SUMMARY BACKGROUND DATA: Laparoscopic
      cholecystectomy is reported to be safe for patients and acceptable as an
      outpatient procedure. Whether this experience can be translated to an academic
      health center or larger hospital is uncertain. Clinical pathways guide the care
      of specific patient populations with the goal of enhancing patient care while
      optimizing resource utilization. The effectiveness of these pathways in achieving
      their goals is not well studied. METHODS: During a 12-month period beginning
      April 1, 1999, all patients eligible for an elective LC (n = 177) participated in
      a clinical pathway developed to transition LC to an outpatient procedure. These
      were compared with all patients undergoing elective LC (n = 208) in the 15 months
      immediately before pathway implementation. Successful same-day discharges,
      reasons for postoperative admission, readmission rates, complications, deaths,
      and patient satisfaction were compared. Average length of stay and total hospital
      costs were calculated and compared. RESULTS: After pathway implementation, the
      proportion of same-day discharges increased significantly, from 21% to 72%.
      Unplanned postoperative admissions decreased as experience with the pathway
      increased. Patient characteristics, need for readmission, complications, and
      deaths were not different between the groups. Patients surveyed were highly
      satisfied with their care. Resource utilization declined, resulting in more
      available inpatient beds and substantial cost savings. CONCLUSIONS:
      Implementation of a clinical pathway for outpatient LC was successful, safe, and
      satisfying for patients. Converting LC to an outpatient procedure resulted in a
      significant reduction in medical resource use, including a decreased length of
      stay and total cost of care.

PMID- 11323511
TI  - Local intra-arterial drug delivery for prevention of restenosis: comparison of
      the efficiency of delivery of different radiopharmaceuticals through a porous
      catheter.
AB  - RATIONALE AND OBJECTIVES: Several radiopharmaceuticals were administered through
      a porous balloon catheter to compare the absolute amount deposited and the
      retention in the vessel wall. The reported efficiency of local drug delivery
      ranges from 0.001% to 0.1%, with poor retention after 24 hours. METHODS: An
      endothelin derivative (n = 6), pertechnetate (n = 6), hexamethylpropylene
      amineoxime (HMPAO) (n = 5), ethyl cysteinate dimer (ECD) (n = 5), and tin colloid
      (n = 5) were labeled with 185 MBq/mL 99m-technetium. After balloon denudation of
      the infrarenal aorta in 27 New Zealand White rabbits, 100 microL of each agent
      was administered through a porous balloon at a pressure of 4 bar. Dynamic and
      static whole-body scintigrams were obtained for 24 hours. The infrarenal aorta
      was excised and the activity calculated in a gamma counter. RESULTS: Apart from
      their retention in the region of local administration, the radiopharmaceuticals
      showed different distribution patterns. The highest regional tracer retention was
      observed with HMPAO. After administration of HMPAO, a significant difference
      between regional (vessel wall plus surrounding tissue: 14.5% of injected dose
      [ID]/24 hours) and local (vessel wall: 1.8% ID/24 hours) delivery was found. In
      contrast, ECD was eliminated quickly (local retention after 24 hours = 0% ID).
      The retention efficiencies were HMPAO > endothelin derivative > tin colloid >
      pertechnetate > ECD. CONCLUSIONS: The different physicochemical and
      pharmacokinetic properties of radiopharmaceuticals resulted in different delivery
      efficiencies after local application.

PMID- 11323512
TI  - Coronary artery motion during the cardiac cycle and optimal ECG triggering for
      coronary artery imaging.
AB  - RATIONALE AND OBJECTIVES: Our purpose was to investigate the motion
      characteristics of the coronary arteries and determine optimal
      electrocardiographic (ECG) trigger time during the cardiac cycle to minimize
      motion artifacts. METHODS: Contrast-enhanced multislice movie studies of electron
      beam tomography (EBT) images were performed on 70 subjects. The EBT datasets,
      which covered an entire cardiac cycle at 58-ms intervals, were acquired for a
      short-axis view of the heart with ECG triggering. The pixel values along x and y
      axes were measured at multiple intervals during the cardiac cycle to establish
      the motion distance and velocity of three major coronary arteries. RESULTS:
      Coronary artery motion varied greatly throughout the cardiac cycle in three major
      coronary arteries and increased with the patient's baseline heart rate. The
      greatest and lowest velocities of coronary arterial movement during the cardiac
      cycle were determined. Based on the lowest velocity of right coronary artery
      movement during the cardiac cycle, the optimal ECG trigger times were located at
      approximately 35% (31.4%-37.6%) or 70% (68.7%-71.4%) of the R-R interval in
      patients whose resting heart rate was < or =70 beats per minute (bpm); at 50%
      (47.2%-61.1%) of the R-R interval in the 71- to 100-bpm group; and at 55% (52.8%
      59.1%) of the R-R interval in the >100-bpm group. Our data demonstrated that the
      motion characteristics of the left circumflex artery were quite similar to those
      of the right coronary artery and that the left anterior descending coronary
      artery had no significant differences in motion throughout the cardiac cycle. A
      minimum scan speed of 35.4 to 75.5 ms per slice is needed to completely diminish
      cardiac motion artifacts (in-plane coronary artery motion with <1-mm
      displacement). CONCLUSIONS: For coronary artery screening, the optimal ECG
      trigger time should be determined according to the patient's heart rate, thus
      greatly reducing motion and motion artifacts during 100-ms acquisitions.

PMID- 11323513
TI  - The use of gadolinium chelates for X-ray digital subtraction angiography.
AB  - RATIONALE AND OBJECTIVES: To evaluate the feasibility and safety of using
      gadolinium chelates for x-ray digital subtraction angiography (DSA) in patients
      with contraindications to iodinated contrast material. METHODS: We performed 30
      DSAs in 22 patients (5 females, 17 males; mean age 64.9 years) with
      contraindications to iodinated contrast media (renal insufficiency: n = 28;
      hyperthyroidism: n = 1; contrast allergy: n = 2). Gadolinium chelates were
      administered as 0.5 mol/L solutions (mean volume of gadolinium chelates per
      patient was 34 +/- 19 mL). Gadolinium chelates were the sole contrast agent in 17
      examinations, were used in conjunction with carbon dioxide (CO2) in 8 studies,
      (mean 212 +/- 226 mL), and were combined with the restricted use of nonionic
      iodinated contrast (mean 12.8 +/- 4.7 mL) in 6 examinations. We carried out 15
      diagnostic angiographies and 15 percutaneous transluminal angioplasties. RESULTS:
      Use of gadolinium chelates allowed us to obtain diagnostic angiographic images in
      all cases. However, the quality of angiograms was inferior compared with that
      obtained with iodinated contrast agents and superior compared with CO2 as the
      contrast material. Adverse events were not noted. Mean serum creatinine was 2.6
      +/- 1.5 mg/dL before and 2.3 +/- 1.0 mg/dL after DSA. No patient developed
      contrast-induced nephropathy. CONCLUSIONS: Gadolinium chelates produce an x-ray
      DSA intermediate in image quality between iodinated contrast and CO2. Digital
      subtraction angiography with intra-arterial gadolinium chelate administration may
      offer an alternative to iodinated contrast material in patients with
      contraindications to iodine.

PMID- 11323514
TI  - Enhancement of cerebral diseases: how much contrast agent is enough? Comparison
      of 0.1, 0.2, and 0.3 mmol/kg gadoteridol at 0.2 T with 0.1 mmol/kg gadoteridol at
      1.5 T.
AB  - RATIONALE AND OBJECTIVES: To determine the clinical dose of gadoteridol
      (ProHance, Bracco-Byk Gulden) to use for the assessment of blood-brain barrier
      breakdown on low-field magnetic resonance (MR) scanners that corresponds to a
      standard dose of gadoteridol on high-field MR scanners. METHODS: This prospective
      study was carried out at four centers. A total of 138 patients with suspected or
      known brain diseases underwent a routine head scan comprising precontrast T2
      weighted turbo spin-echo and T1-weighted spin-echo sequences on a 1.5-T MR
      scanner. After administration of a standard dose of 0.1 mmol/kg gadoteridol, the
      T1-weighted scan was repeated after a delay of 15 to 20 minutes. For continuing
      the examination on a 0.2-T MR scanner (Magnetom OPEN, Siemens), a standard-dose
      T1 spin-echo sequence was started within 30 to 50 minutes of the first injection.
      Then two additional T1-weighted low-field sequences were each started 5 minutes
      after two additional doses of 0.1 mmol/kg gadoteridol. Eighty patients with
      enhancing lesions underwent an intraindividual comparison. Evaluation of the
      overall numbers of lesions detected and of lesion size and character was
      performed on-site as well as off-site by two independent readers. RESULTS: The
      single-dose, low-field sequence detected significantly fewer enhancing lesions
      (80/95 lesions; P < 0.05), particularly metastases and infarctions, than did the
      standard-dose, high-field sequence. No statistically relevant differences (reader
      1: P = 1; reader 2: P = 0.8) were found between the double- and triple-dose, low
      field sequences and the standard-dose, high-field sequence. Primary brain tumors
      were detected by all postcontrast sequences irrespective of the dose.
      CONCLUSIONS: At low field, the clinically equivalent dose to 0.1 mmol/kg
      gadoteridol at high field is 0.2 mmol/kg. A dose of 0.1 mmol/kg gadoteridol is
      less effective and cannot be recommended for use on extremely low-field scanners.

PMID- 11323515
TI  - Comparative effects of ionic and nonionic iodinated low-osmolar contrast media on
      platelet function with the PFA-100 (platelet function analyzer).
AB  - RATIONALE AND OBJECTIVES: This study was designed to (1) compare the effects of
      ionic (ioxaglate) and nonionic (iodixanol and iohexol) iodinated low-osmolar
      contrast media (CM) on platelet function in human whole blood by using the new
      PFA-100trade mark, a "platelet function analyzer"; (2) determine the animal
      species closest to human with regard to platelet reactivity to CM; and (3)
      evaluate which element of the ioxaglate solution supports this activity. METHODS:
      For all studies, platelet adhesion and aggregation were measured using the PFA
      100trade mark system with adenosine diphosphate-primed collagen membrane
      cartridges. Results are shown as the membrane closure time (MCT; the longer the
      MCT, the greater the antiaggregatory effect) and given as medians. Citrated whole
      blood samples from six healthy volunteers were mixed for 1 minute with a 10%
      (vol/vol) solution of ioxaglate, iodixanol, or iohexol or their respective ionic
      and nonionic controls (isotonic saline and mannitol). The test solution/control
      solution ratio for the MCT was calculated for the blood of humans, guinea pigs,
      rabbits, dogs, and rats. Isotonic saline and iso-osmolar (280 mOsm/kg) and
      hyperosmolar (560 mOsm/kg) solutions of meglumine hydrochloride, meglumine
      ioxaglate (560 mOsm/kg), and sodium ioxaglate (600 mOsm/kg) were tested under
      similar conditions. RESULTS: All three CM caused significant prolongation of MCT
      when compared with their respective controls (ioxaglate: 300 seconds, ie, "no
      closure" on the PFA-100trade mark system; iodixanol: 179 seconds; iohexol: 171
      seconds; saline: 115 seconds; mannitol: 118 seconds). The antiplatelet effect of
      ioxaglate was higher than that of iodixanol and iohexol (P < 0.05). The animal
      species tested did not differ significantly from the human species with regard to
      an effect of their blood on MCT. Both ioxaglic acid salts caused a higher
      prolongation of MCT when compared with saline (sodium salt: 259 seconds;
      meglumine salt: 212 seconds; P < 0.05 vs. saline) but not versus the ioxaglate
      commercial solution. Conversely, both iso- and hyperosmolar solutions of
      meglumine hydrochloride (108 and 128 seconds, respectively) did not lengthen MCT
      versus saline, but their MCTs were shorter than that of the commercial solution
      of ioxaglate (P < 0.05). CONCLUSIONS: The ionic CM ioxaglate displayed a greater
      antiaggregatory effect on human platelets than did both iso-osmolar (iodixanol)
      and hyperosmolar (iohexol) nonionic CM. This effect seems to be linked to the
      ioxaglic moiety, because neither osmolality nor sodium or meglumine appeared to
      play a significant role.

PMID- 11323516
TI  - Multiphase-multistep gadolinium-enhanced MR angiography of the abdominal aorta
      and runoff vessels.
AB  - RATIONALE AND OBJECTIVES: To optimize three-dimensional gadolinium magnetic
      resonance angiography (3D-Gd-MRA) of the aorta and runoff vessels by addressing
      fundamentally different requirements for temporal and spatial resolution in a
      single semiautomated examination. METHODS: The technique was designed to obtain
      pure arterial-phase 3D-Gd-MR angiograms with adequate spatial resolution for each
      station while avoiding incomplete enhancement due to delayed filling vessels as
      well as venous overlay. During gadolinium-chelate infusion, a breath-held
      multiphase 3D-Gd-MRA scan was initiated in the aorta by automatic triggering,
      followed by automatic table movement. The acquisition was tailored to the vessels
      of interest by tilting of the 3D volumes. A spatial resolution of 1.7 x 1.2 x 0.8
      mm in the calves was achieved by use of elliptical-centric k-space reordering.
      Signal-to-noise ratio was maximized with a 12-element peripheral vascular coil.
      Twelve patients with peripheral vascular disease were studied. RESULTS: In cases
      of aortic occlusive disease (n = 2), dissections (n = 3), or aneurysms (n = 4),
      substantially delayed fill-in of reconstituted arteries, false lumens, or
      aneurysmal segments occurred, which was detected only on the later 3D-Gd-MRA
      phase. High-resolution arterial-phase scans in the calves were obtained, with
      only one case of substantial venous overlay. Correlation to digital subtraction
      angiography revealed excellent agreement of pathological findings. CONCLUSIONS:
      Multiphase-multistep 3D-Gd-MRA reduces the limitations of standard 3D-Gd-MRA
      techniques with respect to anatomic coverage, spatial resolution, and nonuniform
      arterial vessel enhancement.

PMID- 11323517
TI  - Navi-ball: a new guidance device for CT-directed punctures.
AB  - RATIONALE AND OBJECTIVES: A new navigation system (Navi-Ball) for computed
      tomography (CT)-guided punctures was tested clinically. METHODS: The device
      consists of a transparent hemisphere with an angular scale. The hemisphere is
      fluid filled and contains a bubble indicating the angulation. The system works as
      a circular spirit level. Adapted to the handle of the needle, it allows needle
      adjustment according to the planned puncture path on the CT image. The system was
      tested in 36 patients who had 40 procedures. The needle deviation (in relation to
      the planned course of the needle) was measured in two rectangular planes.
      RESULTS: Without requiring preparation time, the guidance system allowed rapid
      and easy performance of the puncture. First-time needle placement in a double
      angulated approach led to a deviation of the needle from the planned path ranging
      from 0.2 degrees to 4.6 degrees (mean 2.1 degrees, SD 1.4 degrees ) in the axial
      plane and from 0.4 degrees to 4.0 degrees (mean 2.3 degrees, SD 1.2 degrees).
      CONCLUSIONS: This "low-tech" system offers easy to use guidance by a single
      operator and provides for adequate accuracy of first-time needle placement.

PMID- 11323518
TI  - Intracellular Bax translocation after transient cerebral ischemia: implications
      for a role of the mitochondrial apoptotic signaling pathway in ischemic neuronal
      death.
AB  - Activation of terminal caspases such as caspase-3 plays an important role in the
      execution of neuronal cell death after transient cerebral ischemia. Although the
      precise mechanism by which terminal caspases are activated in ischemic neurons
      remains elusive, recent studies have postulated that the mitochondrial cell death
      signaling pathway may participate in this process. The bcl-2 family member
      protein Bax is a potent proapoptotic molecule that, on translocation from cytosol
      to mitochondria, triggers the activation of terminal caspases by increasing
      mitochondrial membrane permeability and resulting in the release of apoptosis
      promoting factors, including cytochrome c. In the present study, the role of
      intracellular Bax translocation in ischemic brain injury was investigated in a
      rat model of transient focal ischemia (30 minutes) and reperfusion (1 to 72
      hours). Immunochemical studies revealed that transient ischemia induced a rapid
      translocation of Bax from cytosol to mitochondria in caudate neurons, with a
      temporal profile and regional distribution coinciding with the mitochondrial
      release of cytochrome c and caspase-9. Further, in postischemic caudate putamen
      in vivo and in isolated brain mitochondria in vitro, the authors found enhanced
      heterodimerization between Bax and the mitochondrial membrane permeabilization
      related proteins adenine nucleotide translocator (ANT) and voltage-dependent
      anion channel. The ANT inhibitor bongkrekic acid prevented Bax and ANT
      interactions and inhibited Bax-triggered caspase-9 release from isolated brain
      mitochondria in vitro. Bongkrekic acid also offered significant neuroprotection
      against ischemia-induced caspase-3 and caspase-9 activation and cell death in the
      brain. These results strongly suggest that the Bax-mediated mitochondrial
      apoptotic signaling pathway may play an important role in ischemic neuronal
      injury.

PMID- 11323519
TI  - Evidence for the involvement of Par-4 in ischemic neuron cell death.
AB  - After a stroke many neurons in the ischemic brain tissue die by a process called
      apoptosis, a form of cell death that may be preventable. The specific molecular
      cascades that mediate ischemic neuronal death are not well understood. The
      authors recently identified prostate apoptosis response-4 (Par-4) as a protein
      that participates in the death of cultured hippocampal neurons induced by trophic
      factor withdrawal and exposure to glutamate. Here, the authors show that Par-4
      levels increase in vulnerable populations of hippocampal and striatal neurons in
      rats after transient forebrain ischemia; Par-4 levels increased within 6 hours of
      reperfusion and remained elevated in neurons undergoing apoptosis 3 days later.
      After transient focal ischemia in mice, Par-4 levels were increased 6 to 12 hours
      after reperfusion in the infarcted cortex and the striatum, and activation of
      caspase-8 occurred with a similar time course. Par-4 immunoreactivity was
      localized predominantly in cortical neurons at the border of the infarct area. A
      Par-4 antisense oligonucleotide protected cultured hippocampal neurons against
      apoptosis induced by chemical hypoxia and significantly reduced focal ischemic
      damage in mice. The current data suggest that early up-regulation of Par-4 plays
      a pivotal role in ischemic neuronal death in animal models of stroke and cardiac
      arrest.

PMID- 11323520
TI  - Paradoxical increase in neuronal DNA fragmentation after neuroprotective free
      radical scavenger treatment in experimental traumatic brain injury.
AB  - The mechanisms and role of nerve cell death after traumatic brain injury (TBI)
      are not fully understood. The authors investigated the effect of pretreatment
      with the oxygen free radical spin trap alpha-phenyl-N-tert-butyl-nitrone (PBN) on
      the number of neurons undergoing apoptosis after TBI in rats. Apoptotic cells
      were identified by the TUNEL method combined with the nuclear stain, Hoechst
      33258, and immunohistochemistry for the active form of caspase-3. Numerous
      neurons became positive for activated caspase 3 and TUNEL in the cortex at 24
      hours after injury, suggesting ongoing biochemical apoptosis. In PBN-treated
      rats, a significantly greater number of cells were found to be TUNEL positive at
      24 hours compared with controls. However, PBN treatment resulted in a reduced
      cortical lesion volume and improved behavioral outcome two weeks after injury.
      The authors conclude that a treatment producing an increase in DNA fragmentation
      in the early phase may be compatible with an overall beneficial effect on outcome
      after TBI. This should be considered in the screening process for future
      neuroprotective remedies.

PMID- 11323521
TI  - Activation of Akt/protein kinase B contributes to induction of ischemic tolerance
      in the CA1 subfield of gerbil hippocampus.
AB  - Apoptosis plays an important role in delayed neuronal cell death after cerebral
      ischemia. Activation of Akt/protein kinase B has been recently reported to
      prevent apoptosis in several cell types. In this article the authors examine
      whether induction of ischemic tolerance resulting from a sublethal ischemic
      insult requires Akt activation. Sublethal ischemia gradually and persistently
      stimulated phosphorylation of Akt-Ser-473 in the hippocampal CA1 region after
      reperfusion. After lethal ischemia, phosphorylation of Akt-Ser-473 showed no
      obvious decrease in preconditioned gerbils but a marked decrease in
      nonconditioned gerbils. Changes in Akt-Ser-473 phosphorylation were correlated
      with changes in Akt activities, as measured by an in vitro kinase assay.
      Intracerebral ventricular infusion of wortmannin before preconditioning blocked
      both the increase in Akt-Ser-473 phosphorylation in a dose-dependent manner and
      the neuroprotective action of preconditioning. These results suggest that Akt
      activation is induced by a sublethal ischemic insult in gerbil hippocampus and
      contributes to neuroprotective ischemic tolerance in CA1 pyramidal neurons.

PMID- 11323522
TI  - Microglia/macrophages proliferate in striatum and neocortex but not in
      hippocampus after brief global ischemia that produces ischemic tolerance in
      gerbil brain.
AB  - The current study determined whether short durations of ischemia that produce
      ischemia-induced tolerance stimulate glial proliferation in brain. Adult male
      gerbils were injected with BrdU (50 mg/kg) and dividing cells were detected using
      immunocytochemistry after sham operations, 2.5 or 5 minutes of global ischemia,
      or ischemia-induced tolerance. The 2.5-minute ischemia and the ischemia-induced
      tolerance did not kill hippocampal CA1 pyramidal neurons, whereas the 5-minute
      ischemia did kill the neurons. At 4 days after 2.5-minute global ischemia, when
      cell proliferation was maximal, BrdU-labeled cells increased in striatum and in
      neocortex, but not in hippocampus. The majority of the BrdU-labeled cells were
      double-labeled with isolectin B4, showing that these dividing cells were
      primarily microglia or macrophages, or both. Similarly, BrdU-labeled
      microglia/macrophages were found in striatum and neocortex but not in hippocampus
      of most animals 4 days after ischemia-induced tolerance (2.5 minutes of global
      ischemia followed 3 days later by 5 minutes of global ischemia). No detectable
      neuronal cell death existed in striatal and cortical regions where the
      microglia/macrophage proliferation occurred. Though 3 of 7 animals subjected to
      2.5 minutes of ischemia showed decreased myelin-associated glycoprotein (MAG)
      immunostaining and increased numbers of adenomatous polyposis coli-stained
      oligodendrocytes in lateral striatum, this did not explain the
      microglia/macrophage proliferation. Data show that ischemia-induced tolerance in
      the gerbil is associated with proliferation of microglia/macrophages in striatum
      and cortex but not in hippocampus. Because there is no apparent neuronal death,
      it is postulated that the microglia/macrophage proliferation occurs in response
      to an unknown nonlethal injury to neurons or glia and may be beneficial.

PMID- 11323523
TI  - Induction of gp91-phox, a component of the phagocyte NADPH oxidase, in microglial
      cells during central nervous system inflammation.
AB  - Gp91-phox is an integral component of the nicotinamide adenine dinucleotide
      phosphate (NADPH) oxidase complex that generates reactive oxygen species (ROS) in
      activated circulating phagocytes. The authors previously demonstrated that gp91
      phox knockout (KO) mice show significant protection from neuronal injury after
      cerebral ischemia--reperfusion injury, suggesting a pivotal role for this enzyme.
      Moreover, results from chimeric mice suggested that elimination of gp91-phox from
      both circulating phagocytes and a putative central nervous system (CNS) source
      were required to confer neuroprotection. In the current study, the authors
      demonstrated gp91-phox-specific immunostaining of perivascular cells in the CNS
      of control rats. However, after transient cerebral ischemia, gp91-phox-positive
      phagocytes were observed within the core ischemic region and activated microglial
      cells were positive in the penumbra. Such activated microglial cells were also
      gp91-phox-positive in the CNS of a chimpanzee with mild meningitis. Finally, in
      humans, both normal adult CNS tissues and isolated fetal microglial cells
      expressed gp91-phox mRNA. These microglia also expressed mRNA for the five other
      known components that comprise the NADPH oxidase complex. These data strongly
      suggest that microglial cells may contain a functionally active NADPH oxidase
      capable of generating ROS during CNS inflammation.

PMID- 11323524
TI  - Ionic mechanisms of aglycemic axon injury in mammalian central white matter.
AB  - The authors investigated ionic mechanisms underlying aglycemic axon injury in
      adult rat optic nerve, a central white matter tract. Axon function was assessed
      using evoked compound action potentials (CAPs). Glucose withdrawal led to delayed
      CAP failure, an alkaline extracellular pH shift, and an increase in extracellular
      [K(+)]. Sixty minutes of glucose withdrawal led to irreversible axon injury.
      Aglycemic axon injury required extracellular calcium; the extent of injury
      progressively declined as bath [Ca(2+)] was decreased. To evaluate Ca(2+)
      movements during aglycemia, the authors recorded extracellular [Ca(2+)]
      ([Ca(2+)](o)) using Ca(2+)-sensitive microelectrodes. Under control conditions,
      [Ca(2+)](o) fell with a similar time course to CAP failure, indicating
      extracellular Ca(2+) moved to an intracellular position during aglycemia. The
      authors quantified the magnitude of [Ca(2+)]o decrease as the area below baseline
      [Ca(2+)]o during aglycemia and used this as a qualitative measure of Ca(2+)
      influx. The authors studied the mechanisms of Ca(2+) influx. Blockade of Na(+)
      influx reduced Ca(2+) influx and improved CAP recovery, suggesting Na(+)-Ca(2+)
      exchanger involvement. Consistent with this hypothesis, bepridil reduced axon
      injury. In addition, diltiazem or nifedipine decreased Ca(2+) influx and
      increased CAP recovery. The authors conclude aglycemic central white matter
      injury is caused by Ca(2+) influx into intracellular compartments through reverse
      Na(+)-Ca(2+) exchange and L-type Ca(2+) channels.

PMID- 11323525
TI  - The maxi-K channel opener BMS-204352 attenuates regional cerebral edema and
      neurologic motor impairment after experimental brain injury.
AB  - Large-conductance, calcium-activated potassium (maxi-K) channels regulate
      neurotransmitter release and neuronal excitability, and openers of these channels
      have been shown to be neuroprotective in models of cerebral ischemia. The authors
      evaluated the effects of postinjury systemic administration of the maxi-K channel
      opener, BMS-204352, on behavioral and histologic outcome after lateral fluid
      percussion (FP) traumatic brain injury (TBI) in the rat. Anesthetized Sprague
      Dawley rats (n = 142) were subjected to moderate FP brain injury (n = 88) or
      surgery without injury (n = 54) and were randomized to receive a bolus of 0.1
      mg/kg BMS-204352 (n = 26, injured; n = 18, sham), 0.03 mg/kg BMS-204352 (n = 25,
      injured; n = 18, sham), or 2% dimethyl sulfoxide (DMSO) in polyethylene glycol
      (vehicle, n = 27, injured; n = 18, sham) at 10 minutes postinjury. One group of
      rats was tested for memory retention (Morris water maze) at 42 hours postinjury,
      then killed for evaluation of regional cerebral edema. A second group of
      injured/sham rats was assessed for neurologic motor function from 48 hours to 2
      weeks postinjury and cortical lesion area. Administration of 0.1 mg/kg BMS-204352
      improved neurologic motor function at 1 and 2 weeks postinjury (P < 0.05) and
      reduced the extent of cerebral edema in the ipsilateral hippocampus, thalamus,
      and adjacent cortex (P < 0.05). Administration of 0.03 mg/kg BMS-204352
      significantly reduced cerebral edema in the ipsilateral thalamus (P < 0.05). No
      effects on cognitive function or cortical tissue loss were observed with either
      dose. These results suggest that the novel maxi-K channel opener BMS-204352 may
      be selectively beneficial in the treatment of experimental TBI.

PMID- 11323526
TI  - Local injection of antisense oligonucleotides targeted to the glial glutamate
      transporter GLAST decreases the metabolic response to somatosensory activation.
AB  - The mechanisms responsible for the local increase in brain glucose utilization
      during functional activation remain unknown. Recent in vitro studies have
      identified a new signaling pathway involving an activation of glial glutamate
      transporters and enhancement of neuron-astrocyte metabolic interactions that
      suggest a putative coupling mechanism. The aim of the present study was to
      determine whether one of the glutamate transporters exclusively expressed in
      astrocytes, GLAST, is involved in the neurometabolic coupling in vivo. For this
      purpose, rats were microinjected into the posteromedial barrel subfield (PMBSF)
      of the somatosensory cortex with GLAST antisense or random phosphorothioate
      oligonucleotides. The physiologic activation was performed by stimulating the
      whisker-to-barrel pathway in anesthetized rats while measuring local cerebral
      glucose utilization by quantitative autoradiography in the PMBSF. Twenty-four
      hours after injection of two different antisense GLAST oligonucleotide sequences,
      and despite the presence of normal whisker-related neuronal activity in the
      PMBSF, the metabolic response to whisker stimulation was decreased by more than
      50%. Injection of the corresponding random sequences still allowed a significant
      increase in glucose utilization in the activated area. The present study
      highlights the contribution of astrocytes to neurometabolic coupling in vivo. It
      provides evidence that glial glutamate transporters are key molecular components
      of this coupling and that neuronal glutamatergic activity is an important
      determinant of energy utilization. Results indicate that astrocytes should also
      be considered as possible sources of altered brain metabolism that could explain
      the distinct imaging signals observed in some pathologic situations.

PMID- 11323527
TI  - Patency of cerebral microvessels after focal embolic stroke in the rat.
AB  - In patients with thrombotic stroke, the occluded artery often reopens over time.
      This results through a natural dissolution of the occluding material, and
      fragments of the material may move downstream to obstruct distal arteries. The
      current study was undertaken to investigate the patency of brain microvessels at
      varying time intervals after injection of a preformed clot into the right
      internal carotid artery of rats. Cerebral microvessels in brain sections were
      visualized using immunohistochemistry for fibronectin (detecting existing
      microvessels) and Evans blue (visualizing perfused microvessels). The percentage
      of patent microvessels was calculated as the number of Evans blue-positive
      microvessels divided by the number of fibronectin-positive microvessels. In
      normal control animals, results showed that 98% +/- 3% (mean +/- SD) of
      microvessels in the cortex and 94% +/- 14% in the striatum were patent. In the
      ischemic animals, immediately after clot injection, microvessels in the cortex
      and striatum were occluded, mainly in the territory irrigated by the middle
      cerebral artery. One hour after clot injection, microvessels had reopened in most
      of the cortex but remained occluded in some portions of the striatum, possibly as
      a result of downstream movement of fragments formed from the original clot. By 3
      hours after clot injection, microvessels in the cortex were patent in all
      animals, whereas in the striatum microvessels were patent in 50% of the animals.
      In the other 50%, small striatal perfusion deficits persisted. At 24 hours after
      clot injection, microvessels were patent in both the cortex and striatum of all
      animals except one. These findings suggest that intracerebral clots dissolve
      spontaneously in a relatively short period of time, but that fragments formed
      from the clot may obstruct more distal blood vessels. It is likely that clot
      fragments lodge in arteries with lower blood flow and poor collateral perfusion,
      where they continue to cause ischemia for a longer duration. These results may in
      part explain the resistance of the striatum to neuroprotective strategies used
      for the treatment of focal cerebral ischemia.

PMID- 11323528
TI  - Relaxant effects of 17-beta-estradiol in cerebral arteries through Ca(2+) entry
      inhibition.
AB  - Estrogens account for gender differences in the incidence and outcome of stroke,
      but it remains unclear to what extent neuroprotective effects of estrogens are
      because of parenchymal or vascular actions. Because reproductive steroids have
      vasoactive properties, the authors assessed the effects and mechanisms of action
      of 17-beta-estradiol in rabbit isolated basilar artery. Cumulative doses of 17
      beta-estradiol (0.3 micromol/L to 0.1 mmol/L) induced concentration-dependent
      relaxation that was larger in basilar than carotid artery, in male than female
      basilar artery, and in KCl-precontracted than UTP-precontracted male basilar
      artery. Endothelium removal did not modify relaxation induced by 17-beta
      estradiol in basilar artery, whereas relaxation induced by acetylcholine (1
      nmol/L to 0.1 mmol/L) was almost abolished. Neither the estrogen receptor
      antagonist ICI 182,780 (1 micromol/L), nor the protein synthesis inhibitor
      cycloheximide (1 micromol/L) affected 17-beta-estradiol-induced relaxations.
      Relaxations induced by the K(+) channel openers NS1619 and pinacidil in the same
      concentration range were greater and lower, respectively, when compared with
      relaxation to 17-beta-estradiol, which was not significantly modified by
      incubation with the K(+) channel blockers charybdotoxin (1 nmol/L and 0.1
      micromol/L) or glibenclamide (10 nmol/L and 1 micromol/L). Preincubation with 17
      beta-estradiol (3 to 100 micromol/L) produced concentration-dependent inhibition
      of CaCl(2)-induced contraction, with less potency than the Ca(2+) entry blocker
      nicardipine (0.01 to 10 nmol/L). The authors conclude that 17-beta-estradiol
      induces endothelium-independent relaxation of cerebral arteries with tissue and
      gender selectivity. The relaxant effect is because of inhibition of extracellular
      Ca(2+) influx to vascular smooth muscle, but activation of estrogen receptors,
      protein synthesis, or K(+) efflux are not involved. Relatively high pharmacologic
      concentrations of 17-beta-estradiol causing relaxation preclude acute vascular
      effects of physiologic circulating levels on the cerebral circulation.

PMID- 11323529
TI  - Relation of apparent diffusion coefficient changes and metabolic disturbances
      after 1 hour of focal cerebral ischemia and at different reperfusion phases in
      rats.
AB  - Changes in apparent diffusion coefficients (ADC) were compared with alterations
      of adenosine triphosphate (ATP) concentration and pH in different phases of
      transient focal cerebral ischemia to study the ADC threshold for breakdown of
      energy metabolism and tissue acidosis during ischemia and reperfusion. Male
      Wistar rats underwent 1 hour of middle cerebral artery occlusion without
      recirculation (n = 3) or with 1 hour (n = 4) or 10 hours of reperfusion (n=5)
      inside the magnet, using a remotely controlled thread occlusion model. ADC maps
      were calculated from diffusion-weighted images and normalized to the preischemic
      value to obtain relative ADC maps. Hemispheric lesion volume (HLV) was determined
      on the last relative ADC maps at different relative ADC thresholds and was
      compared to the HLV measured by ATP depletion and by tissue acidosis. The HLVs,
      defined by ATP depletion and tissue acidosis, were 26.0% +/- 10.6% and 38.1% +/-
      6.5% at the end of ischemia, 3.3% +/- 2.4% and 4.8% +/- 3.5% after 1 hour of
      reperfusion, and 11.2% +/- 4.7% and 10.9% +/- 5.2% after 10 hours of
      recirculation, respectively. The relative ADC thresholds for energy failure were
      consistently approximately 77% of the control value in the three different
      groups. The threshold for tissue acidosis was higher at the end of ischemia (86%
      of control) but was similar to the results obtained for ATP depletion after 1
      hour (78% of control) and 10 hours (76% of control) of recirculation. These
      results indicate that the described relative ADC threshold of approximately 77%
      of control provides a good estimate for the breakdown of energy metabolism not
      only during middle cerebral artery occlusion but also at the early phase of
      reperfusion, when recovery of energy metabolism is expected to occur, or some
      hours later, when development of secondary energy failure was described.

PMID- 11323530
TI  - Two-compartment exchange model for perfusion quantification using arterial spin
      tagging.
AB  - The original well-mixed tissue model for the arterial spin tagging techniques is
      extended to a two-compartment model of restricted water exchange between
      microvascular (blood) and extravascular (tissue) space in the parenchyma. The
      microvascular compartment consists of arterioles, capillaries, and venules, with
      the blood/tissue water exchange taking place in the capillaries. It is shown
      that, in the case of limited water exchange, the individual FAIR (Flow-sensitive
      Alternating Inversion Recovery) signal intensities of the two compartments are
      comparable in magnitude, but are not overlapped in time. It is shown that when
      the limited water exchange is assumed to be fast, flows quantified from the
      signal-intensity difference are underestimated, an effect that becomes more
      significant for larger flows and higher magnetic field strengths. Experimental
      results on cat brain at 4.7 T comparing flow data from the FAIR signal-intensity
      difference with those from microspheres over a cerebral blood flow range from 15
      to 150 mL 100 g(-1) min(-1) confirm these theoretic predictions. FAIR flow values
      with correction for restricted exchange, however, correlate well with the
      radioactive microsphere flow values. The limitations of the approach in terms of
      choice of the intercompartmental exchange rates are discussed.

PMID- 11323532
TI  - A reversible tracer analysis approach to the study of effective dopamine
      turnover.
AB  - Changes in dopamine turnover resulting from disease states such as Parkinson's
      disease may be reflected in corresponding changes in the kinetics of the positron
      emission tomographic tracer [(18)F]fluorodopa. The authors had previously refined
      the conventional irreversible-tracer graphical approach to determine both the
      uptake rate constant K(i) and the rate constant kloss that describes the slow
      loss of the trapped kinetic component. Because these parameters change in the
      opposite sense with disease, their ratios may be more powerfully discriminating
      than either one alone. The ratio k(loss)/K(i) is indicative of effective dopamine
      turnover. Its inverse, K(i)/k(loss), can be interpreted as the effective
      distribution volume (EDV) of the specific uptake compartment referred to the
      fluorodopa concentration in plasma. Here the authors present a new approach to
      the estimation of EDV based on reversible-tracer graphical methods. When
      implemented with a plasma input function, the method evaluates EDV directly. When
      implemented with a tissue input function, the outcome is proportional to the
      ratio of the distribution volumes of the specific uptake and precursor
      compartments. Comparison of the new and previous approaches strongly validates
      this alternative approach to the study of effective dopamine turnover.

PMID- 11323531
TI  - Astrocytes as a predominant cellular site of (99m)Tc-HMPAO retention.
AB  - Technetium-99m-d,l-hexamethylpropylene amine oxime ((99m)Tc-HMPAO) retention in
      the brain monitored by single photon emission computed tomography (SPECT) is
      currently used as a marker of cerebral blood flow. The purported mechanism by
      which (99m)Tc-HMPAO accumulates in the brain is through its intracellular
      conversion from a lipophilic form to more hydrophilic derivatives within the
      brain parenchyma. The issue of the contribution of different cell types on
      (99m)Tc-HMPAO retention was investigated in vitro by studying the accumulation of
      (99m)Tc-HMPAO in primary cultures of mouse cortical astrocytes and neurons.
      Results show that (99m)Tc-HMPAO retention predominates in astrocytes over neurons
      by a factor of approximately 2.5 (0.26 +/- 0.05 vs. 0.095 +/- 0.042 fmol/mg
      protein after 120 minutes, respectively). Diethyl maleate (60 micromol/L),
      ethacrynic acid (1 mmol/L) and buthionine sulfoximine (1 mmol/L), 3 agents which
      significantly reduced glutathione levels also decreased (99m)Tc-HMPAO retention
      in both astrocytes (29%, 3%, and 46% of control, respectively) and neurons (69%,
      11% and 63% of control). Decrease did not always correlate with glutathione
      levels, however, which suggests that other factors could be involved. The
      possibility that cell energy status determines (99m)Tc-HMPAO retention was also
      assessed. Agents that activate (glutamate, azide) or inhibit (cytochalasin B)
      glucose utilization in astrocytes, as measured by the (3)H-2-deoxyglucose method,
      were without effect on (99m)Tc-HMPAO retention. In conclusion, the data presented
      indicate that astrocytes may constitute a prominent site of (99m)Tc-HMPAO
      retention and most likely contribute significantly to the SPECT signal. In
      addition, the data also suggest that specific alterations in glial cell
      metabolism could explain flow-independent changes in (99m)Tc-HMPAO retention in
      the brain as observed by SPECT in some pathologies.

PMID- 11323533
TI  - Tendon healing stimulated by injected CDMP-2.
AB  - Tendon healing stimulated by injected CDMP-2. Med. Sci. Sports Exerc., Vol. 33,
      No. 5, 2001, pp. 685-687. INTRODUCTION: CDMP-2 is a member of the TFG-beta super
      family. It is known to induce bone and cartilage formation but has also been
      shown under certain conditions to induce a tendon- and ligament-like tissue. The
      purpose of this study was to find possibilities for improvement of Achilles
      tendon repair during nonoperative treatment, by local injections of CDMP-2.
      METHODS: Fifty rats had a 3-mm segment of the Achilles tendon removed. Six hours
      postoperatively, CDMP-2 was injected locally into the defect at a dose of 0, 2,
      10, or 50 microg. Eight days after the operation, the rats were killed and the
      tensile strength of the repairing tendons was measured with a materials testing
      machine. RESULTS: After 8 d, the CDMP-2-treated tendons were 39% stronger than
      the controls (P = 0.0008). CONCLUSION: One single injection CDMP-2 can augment
      tendon repair. Mechanical stimulation is of great importance for tissue
      differentiation and tendon repair. The tendons in our model were mechanically
      loaded during healing and this might explain why CDMP-2 injections induced a
      strong tendon-like tissue instead of bone or cartilage in this model.

PMID- 11323534
TI  - Kyphosis in active and sedentary postmenopausal women.
AB  - EAGAN, M. S., and D. A. SEDLOCK. Kyphosis in active and sedentary postmenopausal
      women. Med. Sci. Sports Exerc., Vol. 33, No. 5, 2001, pp. 688-695. PURPOSE: This
      study examined kyphosis in relation to self-reported activity level (sedentary,
      active) and activity type (weight-bearing land, nonweight-bearing water) in 61
      postmenopausal women aged 60-78 yr. METHODS: Specifically, we measured kyphosis,
      muscle strength (defined as back extensor (BES) and grip (GS) strength), total
      calcium intake, body fat, height lost since age 30 (HtLost), current activity
      level for household, leisure and sport activities and their total, as well as
      occupational and physical activity history and their total. RESULTS: No
      significant differences (P > 0.05) were found for any variables when subjects
      were divided into sedentary (N = 18), land (N = 29), and water (N = 14) groups;
      exercisers (N = 43) and nonexercisers (N = 18); or between the top and bottom
      tertiles of lifetime active (N = 20) and inactive (N = 20) women. Stepwise
      multiple regression yielded body fat as the single best predictor of kyphosis
      accounting for 6.9% of the total variance (P < 0.04) with the resulting equation:
      kyphosis (degrees) = 22.919 + 0.627*body fat (%) + 0.852*HtLost (cm) + 2.881E
      0.03*total calcium intake (mg) (r2 = 0.22, SEE = 7.7). Significant relationships
      (P < 0.05) included kyphosis with body fat (r = 0.26) and HtLost with age (r =
      0.50). Relationships (P < 0.05) regarding muscle strength included: GS and BES
      with age (r = -0.38, -0.30), HtLost (r = -0.39, -0.36), and occupational activity
      history (r = 0.28, 0.35), as well as BES with household activity and total
      activity history (r = 0.28, 0.30). Physical activity history was related (P <
      0.05) to current sport, leisure, and total activity history (r = 0.37, 0.42,
      0.93, respectively). CONCLUSION: Women who are active when younger seem to be
      active and stronger as older adults. However, this does not seem to impact
      kyphosis. The measured variables accounted for a small proportion of kyphosis
      variance, suggesting that more potent causative factors of this spinal
      malformation exist.

PMID- 11323535
TI  - Muscle transplant in the rabbit's Achilles tendon.
AB  - Achilles tendinopathy (AT) is a degenerative disorder resulting from functional
      overload, especially during running and jumping, with some inflammatory features
      at the insertions, bursae, and paratenon. The Achilles tendon is poorly
      vascularized, especially in the middle third, and the consequent slow metabolic
      rate allows it to work at very low oxygen tensions but prevents on the other hand
      a rapid healing. PURPOSE: To create an animal model to study a novel surgical
      technique employed in AT: transplanting some fibers of the soleus muscle into the
      tendon in order to improve its vascularization and healing and to study the
      histological appearance of the soleus graft incorporated in the tendon. METHODS:
      We operated on 10 white New Zealand rabbits (eight rabbits underwent the
      procedure, two rabbits the sham operation with incision of the tendon without
      graft). Two animals were euthanized at 1 wk, 1, 2, and 3 months. RESULTS:
      Histology showed that after 3 months the muscle fibers were still viable within
      the tendons, interspersed within connective tissue fibers. Tendon and muscle
      tissues were intimately fused. CONCLUSIONS: The persistence of the soleus muscle
      pedicle graft within the Achilles tendon tissue is an index of sound blood
      supply. This surgical model is suitable for application in further studies on
      tendon healing.

PMID- 11323536
TI  - Effect of ketoprofen on muscle function and sEMG activity after eccentric
      exercise.
AB  - PURPOSE: This study examined whether ketoprofen, a nonsteroidal anti-inflammatory
      drug, attenuated muscle soreness (SOR), improved maximal isometric force (MIF)
      recovery, and/or altered myoelectric activity after high-force eccentric
      exercise. METHODS: 48 subjects were randomly assigned to one of four groups: CON:
      no exercise/no drug (N = 12); PLA: exercise + placebo (N = 12); TRT-100: exercise
      + 100 mg oral ketoprofen (N = 12); and TRT-25: exercise + 25 mg oral ketoprofen
      (N = 12). PLA, TRT-100, and TRT-25 were administered in a double-blind fashion.
      Baseline measurements of SOR, MIF, and surface electromyographic (EMG) amplitude
      were taken, and PLA, TRT-100, and TRT-25 performed 50 maximal eccentric
      contractions of the elbow flexors; 36 h later, subjects reporting moderate
      soreness were given ketoprofen or placebo and SOR measures were taken hourly for
      8 h. EMG amplitude was assessed during MIF before dosing and again 8 h later and
      during submaximal contractions of 5%, 10%, and 20% of MIF before dosing and
      hourly for 8 h. RESULTS: Eccentric exercise increased myoelectric activity during
      submaximal force measurements in PLA, TRT-100, and TRT-25 in all conditions.
      Ketoprofen had no effect on reducing this increase in EMG activity. Ketoprofen
      attenuated perceived SOR (P < 0.05) and enhanced MIF recovery (P < 0.05) compared
      with placebo. TRT-100 and TRT-25 demonstrated 10% and 19% reductions in SOR,
      respectively, and 16% and 9% increases in MIF, respectively, whereas PLA
      demonstrated a 1% increase in SOR and 9% decrease in MIF over 8 h. CONCLUSION:
      Ketoprofen treatment after muscle damaging exercise reduces muscle soreness and
      improves force recovery.

PMID- 11323537
TI  - Circuit training provides cardiorespiratory and strength benefits in persons with
      paraplegia.
AB  - PURPOSE: This study tested the safety and the effects of circuit resistance
      training (CRT) on peak upper extremity cardiorespiratory endurance and muscle
      strength in chronic survivors of paraplegia due to spinal cord injury. METHODS:
      Ten men with chronic neurologically complete paraplegia at the T5-L1 levels
      participated in the study. Subjects completed 12 wk of CRT, using a series of
      alternating isoinertial resistance exercises on a multi-station gym and high
      speed, low-resistance arm ergometry. Peak arm ergometry tests, upper extremity
      isoinertial strength testing, and testing of upper extremity isokinetic strength
      were all performed before and after training. RESULTS: None of the subjects
      suffered injury from exercise training. Significant increases were observed in
      peak oxygen consumption (29.7%, P < 0.01), time to fatigue (P < 0.01), and peak
      power output during arm testing (P < 0.05). Significant increases in isoinertial
      strength for the training maneuvers ranged from 11.9% to 30% (Ps < 0.01).
      Significant increases in isokinetic strength were experienced for shoulder joint
      internal rotation, extension, abduction, adduction, and horizontal adduction (Ps
      < 0.05). CONCLUSION: Chronic survivors of paraplegia safely improve their upper
      extremity cardiorespiratory endurance and muscle strength when undergoing a short
      term circuit resistance training program. Gains in fitness and strength exceeded
      those usually reported after either arm endurance exercise conditioning or
      strength training in this subject population.

PMID- 11323539
TI  - Effect of exercise training on metallothionein levels of hypertensive rats.
AB  - PURPOSE: Because oxidative stress may be involved in arterial hypertension by
      affecting the balance between relaxing and contracting factors of vascular smooth
      muscle, the training-induced adaptation of antioxidant defenses could be
      implicated in the antihypertensive effect of chronic exercise. It has been
      suggested that metallothionein (MT), a metal-binding protein, plays an
      antioxidant role in mammals. The aim of this experiment was to study whether
      chronic exercise (swimming) influences both the development of arterial
      hypertension in spontaneously hypertensive rats (SHR) and the modification of MT
      levels. METHOD: Male SHR and Wistar Kyoto (WKY) rats as control were trained to
      swim 1 h.d-1 5 d.wk-1 for 8 wk and sacrificed 72 h after the last exercise
      period. MT and total thiol levels were then measured. RESULTS: Exercise training
      1) reduced systolic blood pressure and heart rate in both SHR WKY rats, and 2)
      was associated with a decrease in hepatic and cardiac MT levels; there was an
      increase in the aortic MT amounts in exercised SHR only. No modifications were
      noted in the gastrocnemius muscle or kidneys. In exercised animals, total thiols
      were lower in the liver but not in kidneys. CONCLUSION: Chronic exercise induced
      a reduction in arterial hypertension development in SHR rats and an adaptation of
      the MT levels in cardiac, hepatic, and aortic tissues. Further experiments are
      needed to pinpoint the role of the MT in these two cases in which oxidative
      stress occurs.

PMID- 11323538
TI  - Exercise reduces daily fatigue in women with breast cancer receiving
      chemotherapy.
AB  - PURPOSE: Cancer treatment-related fatigue is the most prevalent and distressing
      symptom of cancer therapy. Interventions to minimize fatigue are needed. The
      purpose of this study was to examine the relationship between exercise and
      fatigue over the first three cycles of chemotherapy in women receiving either
      cyclophosphamide, methotrexate, and fluorouracil (CMF) or doxorubicin and
      cyclophosphamide (AC) for breast cancer. METHODS: Seventy-two newly diagnosed
      women with breast cancer were instructed in a home-based moderate-intensity
      exercise intervention. Measures of functional ability, energy expenditure, and
      fatigue were obtained at baseline and posttest. Subjects maintained daily records
      of four types of fatigue, and exercise duration, intensity, and type. RESULTS:
      Exercise significantly reduced all four levels of fatigue (P < 0.01). As the
      duration of exercise increased, the intensity of fatigue declined (P < 0.01).
      There was a significant carry-over effect of exercise on fatigue, but the effect
      lasted only 1 d. The level of fatigue at study entry was not associated with
      number of days of exercise or amount of exercise a woman engaged in. CONCLUSIONS:
      The impact of exercise on fatigue was significant and suggests the effectiveness
      of a low- to moderate-intensity regular exercise program in maintaining
      functional ability and reducing fatigue in women with breast cancer receiving
      chemotherapy.

PMID- 11323540
TI  - Exercise training increases heat shock protein in skeletal muscles of old rats.
AB  - PURPOSE: The effects of chronic exercise training on the expression of heat shock
      protein (HSP) in skeletal muscle of senescent animals are unknown. Therefore, the
      purpose of this study was to investigate the effects of chronic exercise training
      on skeletal muscle HSP expression in both young and old rats. METHODS: Young
      adult (3 months) and old (23 months) female Fisher 344 rats were assigned to
      either a sedentary control or an endurance exercise trained group (N = 6 per
      group). Exercised animals ran (60 min.d-1, 5 d.wk-1) on a treadmill at
      approximately 77% VO2peak for 10 wk. After completion of the training program,
      the soleus (SOL), plantaris (PL), and the red (RG) and white portions (WG) of the
      gastrocnemius muscles were excised, and citrate synthase (CS) activity and the
      relative levels of HSP72 were determined. RESULTS: Training resulted in increases
      (P < 0.05) in VO2peak in both young (67.6 +/- 3.1 vs 86.9 +/- 1.6 mL.kg-1.min-1)
      and old animals (54.5 +/- 1.8 vs 68.2 +/- 2.2 mL.kg-1.min-1). Training increased
      CS activity and the relative levels of HSP72 (P < 0.05) in all four skeletal
      muscles in both young and old animals. Specifically, compared with age-matched
      sedentary controls, exercise training resulted in increased (P < 0.05) levels of
      HSP72 in skeletal muscles of both young (SOL + 22%, PL +94%, RG + 44%, WG + 243%)
      and old animals (SOL +15%, PL +73%, RG +38%, WG +150%). CONCLUSIONS: These
      findings reveal that the exercise-induced accumulation of HSP72 in skeletal
      muscle differs between fast and slow muscles. Further, these data indicate that
      the exercise-induced accumulation of HSP72 in highly oxidative skeletal muscles
      (SOL and RG) is similar between young and old animals. In contrast, aging is
      associated with a blunted expression of HSP72 in fast skeletal muscles (PL and
      WG) in response to chronic exercise.

PMID- 11323541
TI  - Left ventricular function and perfusion in elderly endurance athletes.
AB  - PURPOSE: To study the extent to which lifelong physical training can affect
      cardiovascular capacity, left ventricular function, and myocardial perfusion in
      elderly men. METHODS AND RESULTS: Ten healthy male veteran endurance athletes
      aged 73 +/- 3 yr (mean +/- SD) and a control group of 12 sedentary or moderately
      physically active healthy subjects aged 75 +/- 2 yr were studied.
      Echocardiographic examinations at rest and exercise stress tests were performed.
      Gated blood pool scans and myocardial perfusion scintigraphy were recorded at
      rest and during exercise. Maximal VO2 was 41 +/- 7 mL.kg-1.min-1 in the athletes
      and 26 +/- 5 mL.kg-1.min-1 in the controls (P < 0.001). Echocardiographic
      measures of systolic and diastolic function at rest were better in the athletes.
      The ejection fraction during exercise was also higher in the athletes (P =
      0.003). Seven of the 10 athletes, but none of the controls, had pathological
      myocardial perfusion findings. CONCLUSIONS: By endurance training, a high level
      of physical capacity can be maintained late in life. The superior cardiovascular
      function in the veteran athletes, compared with the untrained controls was due to
      both better systolic and diastolic left ventricular function. Myocardial
      perfusion defects in athletes should be judged with caution, as this finding is
      common both in veteran athletes and as previously shown, in young athletes.

PMID- 11323542
TI  - Effects of iron repletion on blood volume and performance capacity in young
      athletes.
AB  - PURPOSE: The purpose of this study was to find out whether iron repletion leads
      to an increase in red blood cell volume (RBV) and performance capacity in iron
      deficient nonanemic athletes. METHODS: 40 young elite athletes (13-25 yr) with
      low serum ferritin (< 20 microg.L-1) and normal hemoglobin (males > 13.5 g.dL-1,
      females > 11.7 g.dL-1) were randomly assigned to 12-wk treatment with either
      twice a day ferrous iron (equivalent to 2 x 100 mg elemental iron) or with
      placebo using a double blind method. Before and after treatment, hematological
      measures and parameters of iron status were determined in venous blood. RBV,
      blood volume (BV), and plasma volume (PV) were measured by CO rebreathing. For
      determination of the aerobic and anaerobic capacity (maximal accumulated oxygen
      deficit, MAOD), the athletes performed an incremental as well as a highly
      intensive treadmill test. RESULTS: After 12 wk, ferritin levels were within the
      normal range in the iron-treated group (IG) with a significant (P < 0.001) mean
      increase by 20 microg.L-1 opposed to a slight nonsignificant decrease in the
      placebo group (PG). RBV did not change significantly in either group nor did any
      of the hematological measures. However, only in IG there were significant
      increases in VO2max and in O2 consumption in the MAOD test. MAOD and maximal
      capillary lactate concentration remained unchanged in both treatment groups.
      CONCLUSIONS: The results indicate that in young elite athletes with low serum
      ferritin and normal hemoglobin concentration iron supplementation leads to an
      increase in maximal aerobic performance capacity without an augmentation of RBV.

PMID- 11323543
TI  - Blood and urinary measures of hydration status during progressive acute
      dehydration.
AB  - PURPOSE: To determine whether: a) plasma osmolarity (Posm) is sensitive to small
      incremental changes in hydration status, b) urine specific gravity (Usg) can
      accurately identify a state of euhydration, c) Usg is a sensitive indicator of a
      change in hydration status, and d) Usg correlates with Posm. METHODS: Euhydrated
      (Posm = 288 +/- 4 mOsm.L-1) subjects (N = 12) were dehydrated by 5% of their body
      weight via exercise in the heat (40 degrees C, 20% RH). Posm, urine osmolarity
      (Uosm), and Usg were measured at 1%, 3%, and 5% dehydration, and 30 and 60 min of
      recovery (rec). Subjects consumed water in recovery equal to their loss of body
      weight. RESULTS: Posm increased incrementally with each successive increase in
      percent body weight loss (%BWL). Usg was not significantly different from
      baseline until 3% BML. Uosm was not significantly different from baseline until
      5% BWL. Usg correlated moderately (r = 0.46, P > 0.10) with Posm but reasonably
      well (r = 0.68, P < 0.02) with Uosm. CONCLUSIONS: Posm accurately identifies a
      state of euhydration and is sensitive to changes in hydration status during acute
      dehydration and rehydration. Usg and Uosm are also sensitive to changes in
      hydration status but lag behind during periods of rapid body fluid turnover and
      therefore correlate only moderately with Posm during acute dehydration.

PMID- 11323545
TI  - Physical fitness and activity as separate heart disease risk factors: a meta
      analysis.

PMID- 11323544
TI  - Physical fitness and activity as separate heart disease risk factors: a meta
      analysis.
AB  - OBJECTIVE: Public health policies for physical activity presume that the greatest
      health benefits are achieved by increasing physical activity among the least
      active. This presumption is based largely on studies of cardiorespiratory
      fitness. To assess whether studies of cardiorespiratory fitness are germane to
      physical activity guidelines, we compared the dose-response relationships between
      cardiovascular disease endpoints with leisure-time physical activity and fitness
      from published studies. DATA SOURCES: Twenty-three sex-specific cohorts of
      physical activity or fitness (representing 1,325,004 person-years of follow-up),
      cited in Tables 4-1 and 4-2 of the Surgeon General's Report. DATA SYNTHESIS:
      Relative risks were plotted as a function of the cumulative percentages of the
      samples when ranked from least fit or active, to most fit or active. To combine
      study results, a weighted average of the relative risks over the 16 physical
      activity or seven fitness cohorts was computed at every 5th percentile between 5
      and 100%. The analyses show that the risks of coronary heart disease or
      cardiovascular disease decrease linearly in association with increasing
      percentiles of physical activity. In contrast, there is a precipitous drop in
      risk occurring before the 25th percentile of the fitness distribution. As a
      consequence of this drop, there is a significant difference in the risk reduction
      associated with being more physically active or physically fit (P < or = 0.04).
      CONCLUSIONS: Being unfit warrants consideration as a risk factor, distinctly from
      inactivity, and worthy of screening and intervention. Formulating physical
      activity recommendations on the basis of fitness studies may inappropriately
      demote the status of physical fitness as a risk factor while exaggerating the
      public health benefits of moderate amounts of physical activity.

PMID- 11323546
TI  - Tracking of physical fitness during adolescence: a panel study in boys.
AB  - PURPOSE: To investigate the tracking in physical fitness (PF) viewed as a whole,
      a multidimensional trait of the subject, and to establish the stability of each
      factor of PF in adolescence from the perspective of a panel study using the
      structural equation modeling approach. METHODS: From a sample of 454 boys
      followed from 12 to 18 yr of age of the Leuven Growth Study, we considered only
      three consecutive measurement occasions with a mean age of 12.76, 14.69, and
      17.73 yr. Physical fitness was evaluated by means of a battery composed of the
      following tests: plate tapping, sit and reach, vertical jump, arm pull, leg
      lifts, bent arm hang, and shuttle run. Structural equation models were fitted to
      the data, namely autoregressive models with latent variables. These models were
      used to quantify the tracking of PF as a whole and also of the individual marker
      variables of fitness. RESULTS: Stability estimates of PF as a whole are rather
      high, beta21 = 0.86 and beta32 = 0.68, with an explained variance of 74% and 73%,
      respectively. Tracking coefficients represented by disattenuated autocorrelations
      among the fitness factor gave high results: r1,2 = 0.86; r1,3 = 0.78; and r2,3 =
      0.85. CONCLUSIONS: Physical fitness as a whole is highly stable in adolescent
      years and very predictable from early years. The same is observed for each factor
      of fitness. Moreover, autoregressive models within the context of structural
      equation modeling are better suited than simple Pearson or Spearman
      autocorrelations to study the tracking problem of PF.

PMID- 11323547
TI  - Physical activity and cognitive decline, the role of the apolipoprotein e4
      allele.
AB  - PURPOSE: The purpose of this study was to investigate the association between
      level of physical activity and risk of cognitive decline at older age and its
      variation across carriers and noncarriers of the apolipoprotein e4 allele.
      METHODS: The association was studied in a cohort of 347 elderly Dutch men. Mean
      age of the study subjects was 74.6 +/- 4.3 yr in 1990. Physical activity was
      categorized in "maximal 1 h per day" versus "more than 1 h per day." Cognitive
      decline was defined as a drop MMSE score > 3 points between 1990 and 1993.
      RESULTS: After adjusting for age, education, alcohol consumption, smoking and
      cognitive functioning at baseline, subjects with maximal 1 h of physical activity
      per day had a two-fold increased risk of cognitive decline (OR 2.0, 95% CI: 0.9
      4.8) as compared with the rest. Risk of cognitive decline was particularly strong
      in carriers of the APOE*4 allele (adjusted OR 3.7, 95% CI: 1.1-12.6). CONCLUSION:
      The authors conclude that promotion of physical activity at older age may reduce
      the risk of cognitive decline. The existence of subgroups with a particularly
      high risk may have important implications for prevention strategies.

PMID- 11323548
TI  - Current injury or disability as a barrier to being more physically active.
AB  - PURPOSE: To assess the extent to which a current injury or disability is a
      significant barrier to being more active. METHODS: Data on current injury or
      disability as a reported barrier to being more physically active were extracted
      from an urban-representative population survey. Multivariate logistic regression
      analyses assessed the association between gender, educational attainment, age,
      body mass index, and current physical activity levels with injury or disability
      as a barrier. RESULTS: Twenty percent of the survey respondents gave current
      injury or disability as a reason for not being more active. There were no
      significant differences between male and female subjects. There was a significant
      trend toward a higher reporting of current injury or disability as a barrier,
      with increasing age (P < 0.001). High body mass index (P < 0.001) and current
      physical activity levels (P < 0.05) were significantly related to the injury or
      disability barrier. The only variables significantly independently associated in
      multivariate logistic regression analyses were age and body mass index.
      CONCLUSIONS: Current injury or disability as a barrier to increased physical
      activity was independently, and significantly, associated with both age and body
      mass index, after adjusting for other variables. The promotion of increased
      physical activity to older and overweight groups should focus on safe activities
      that do not aggravate previous injuries or disabilities.

PMID- 11323549
TI  - Human hamstring muscles adapt to eccentric exercise by changing optimum length.
AB  - PURPOSE: It is now established that unaccustomed eccentric exercise leads to
      muscle fiber damage and to delayed-onset muscle soreness (DOMS) in the days after
      exercise. However, a second bout of eccentric exercise, a week after the first,
      produces much less damage and soreness. The purpose of this study was to provide
      evidence from muscle mechanical properties of a proposed mechanism for this
      training effect in human hamstring muscles. METHODS: The eccentric exercise
      involved 12 sets of 6 repetition "hamstring lowers," performed on specially
      designed equipment. Hamstring angle-torque curves were constructed for each of 10
      subjects (8 male and 2 female) while they performed maximum voluntary knee
      extension and flexion movements on an isokinetic dynamometer. Testing sessions
      were performed over the week before eccentric exercise, immediately post
      exercise, and daily, up to 8 d post exercise. Subject soreness ratings and leg
      girth measurements were also made post exercise. Six subjects performed a second
      bout of eccentric exercise, 8 d after the first, and measurements were continued
      up to 10 d beyond that. RESULTS: There was a significant shift in the optimum
      angle for torque generation (Lo), to longer muscle lengths immediately post
      exercise (7.7 degrees +/- 2.1 degrees, P < 0.01), indicating an increase in
      series compliance within some muscle fibers. Subsequent measurements showed
      increases in leg girth and some muscle soreness, suggesting muscle damage. The
      shift in Lo persisted, even after other injury parameters had returned to normal,
      consistent with a training effect. Subjects also showed fewer signs of muscle
      damage after the second exercise bout. CONCLUSION: This is the first study to
      show a sustained shift in optimum angle of human muscle as a protective strategy
      against injury from eccentric exercise. Implications of this work for athletes,
      particularly those prone to hamstring strains are discussed.

PMID- 11323550
TI  - Metabolic reaction after concentric and eccentric endurance-exercise of the knee
      and ankle.
AB  - PURPOSE: Power training plays an essential part in many sport disciplines. The
      importance of eccentric power training remains a matter of controversial
      discussion. The objective of this study was therefore to investigate the
      difference in metabolic reaction between eccentric and concentric stress in
      comparable work. METHODS: Sixty-four men between 22 and 60 yr of age performed
      maximum isokinetic 1-min endurance tests of the knee and ankle each in concentric
      (180 degrees.s-1) and eccentric (60 degrees.s-1) modes with comparable total area
      of contraction-time curve (NS). Higher strength values (mean peak torque, P <
      0.01), lower fatigue (fatigue index, P < 0.001), lower increase in lactate (P <
      0.01), and lower ammonia production (P < 0.01) were found in eccentric than in
      concentric exercise, independent of the joint. The eccentric form of stress
      showed lower decrease and thus age-dependence in maximum strength and in fatigue
      than the concentric form. RESULTS: The results permit the conclusion that
      eccentric exercise leads to less fatigue and lower lactate and ammonia reaction
      than concentric exercise in comparable work levels. Variable visco-elastic
      properties of the muscle fibers themselves with additive passive strength in
      eccentric mode is considered as the cause. CONCLUSIONS: It remains uncertain
      whether the lower metabolic stress might be useful during the training process. A
      greater scope of training and increased number of training stimuli might be
      applied in primarily eccentric forms of exercise.

PMID- 11323551
TI  - Exercise intensity and load during mass-start stage races in professional road
      cycling.
AB  - PURPOSE: To evaluate exercise intensity and load during mass-start stages in
      professional road cycling, using competition heart rate (HR) recordings. METHODS:
      Seventeen world-class cyclists performed an incremental laboratory test during
      which maximal power output (Wmax), maximal HR (HRmax), onset of blood lactate
      accumulation (OBLA), lactate threshold (LT), and a HR-power output relationship
      were assessed. An OBLAZONE (HROBLA +/- 3 beats.min-1) and an LTZONE (HRLT +/- 3
      beats.min-1) were described. HR was monitored during 125 flat (< 13 km uphill, <
      800-m altitude change; FLAT), 99 semi-mountainous (13-35 km uphill, 800- to 2000
      m altitude change; SEMO), and 86 high-mountain (> 35 km uphill, > 2000-m altitude
      change; HIMO) stages. Each cyclist's competition power output was estimated from
      competition HR and individual HR-power output relationships. Competition training
      impulse (TRIMP) values and time spent at "easy," "moderate," and "hard" zones
      were estimated from HR and race duration. RESULTS: Average %HRmax were 61 +/- 5%,
      58 +/- 6%, and 51 +/- 7% in HIMO, SEMO, and FLAT stages, respectively, and
      estimated average power outputs were 246 +/- 44, 234 +/- 43, and 192 +/- 45 W.
      Competition HR values relative to HROBLA and HRLT were, respectively, 69 +/- 6,
      79 +/- 9% in HIMO; 65 +/- 7, 74 +/- 11% in SEMO; and 57 +/- 8, 65 +/- 10% in FLAT
      stages. The amount of TRIMP in HIMO, SEMO, and FLAT stages were, respectively,
      215 +/- 38, 172 +/- 31, and 156 +/- 31. Percentage time spent in the "moderate"
      and "hard" zones was highest in HIMO (22 +/- 14, 5 +/- 6%) followed by SEMO (15
      +/- 13, 5 +/- 5%) and FLAT (9 +/- 7, 2 +/- 2%) stages. CONCLUSIONS: %HRmax, time
      distribution around HROBLA and HRLT, TRIMP, and load zones reflected the
      physiological demands of different mass-start cycling stage categories. The
      knowledge of these demands could be useful for planning precompetition training
      strategies.

PMID- 11323552
TI  - Inspiratory muscle training improves rowing performance.
AB  - PURPOSE: To investigate the effects of a period of resistive inspiratory muscle
      training (IMT) upon rowing performance. METHODS: Performance was appraised in 14
      female competitive rowers at the commencement and after 11 wk of inspiratory
      muscle training on a rowing ergometer by using a 6-min all-out effort and a 5000
      m trial. IMT consisted of 30 inspiratory efforts twice daily. Each effort
      required the subject to inspire against a resistance equivalent to 50% peak
      inspiratory mouth pressure (PImax) by using an inspiratory muscle training
      device. Seven of the rowers, who formed the placebo group, used the same device
      but performed 60 breaths once daily with an inspiratory resistance equivalent to
      15% PImax. RESULTS: The inspiratory muscle strength of the training group
      increased by 44 +/- 25 cm H2O (45.3 +/- 29.7%) compared with only 6 +/- 11 cm H2O
      (5.3 +/- 9.8%) of the placebo group (P < 0.05 within and between groups). The
      distance covered in the 6-min all-out effort increased by 3.5 +/- 1.2% in the
      training group compared with 1.6 +/- 1.0% in the placebo group (P < 0.05). The
      time in the 5000-m trial decreased by 36 +/- 9 s (3.1 +/- 0.8%) in the training
      group compared with only 11 +/- 8 s (0.9 +/- 0.6%) in the placebo group (P <
      0.05). Furthermore, the resistance of the training group to inspiratory muscle
      fatigue after the 6-min all-out effort was improved from an 11.2 +/- 4.3% deficit
      in PImax to only 3.0 +/- 1.6% (P < 0.05) pre- and post-intervention,
      respectively. CONCLUSIONS: IMT improves rowing performance on the 6-min all-out
      effort and the 5000-m trial.

PMID- 11323553
TI  - Weight loss methods of high school wrestlers.
AB  - PURPOSE: The purpose of this investigation was to assess the weight loss
      practices of Michigan high school wrestlers at all levels of competition.
      METHODS: A two-page survey was designed to assess weight loss behaviors of high
      school wrestlers. It was mailed by the Michigan High School Athletic Association
      (MHSAA) midway through the wrestling season to all Michigan high schools
      participating in interscholastic wrestling. RESULTS: Completed surveys were
      received from 2532 wrestlers. Wrestlers lost an average of 6 pounds during the
      season. Over 50% of wrestlers lost more than 5 pounds; 27% of wrestlers lost at
      least 10 pounds; 72% of wrestlers engaged in at least one potentially harmful
      weight loss method each week of the wrestling season; 52% used at least two
      methods each week; 12% used at least five methods each week. Weekly use of
      laxatives, diet pill, or diuretics was reported by 2% of wrestlers. Vomiting to
      lose weight was done at least weekly by 2% of wrestlers. Wrestlers who engaged in
      at least one rapid weight loss method per week lost more weight, began wrestling
      at an earlier age, and reported more binge eating compared with wrestlers who did
      not report weekly rapid weight loss. CONCLUSION: The majority of Michigan high
      school wrestlers engaged in at least one potentially harmful weight loss method
      each week of the wrestling season. Fasting and various methods of dehydration
      were the primary methods of rapid weight loss. Wrestlers who lost weight each
      week were more likely to binge eat. Potentially harmful weight loss practices
      were found to be common at all grades and success levels.

PMID- 11323554
TI  - Effect of creatine loading on long-term sprint exercise performance and
      metabolism.
AB  - PURPOSE: This study examined whether creatine (Cr) supplementation could enhance
      long-term repeated-sprint exercise performance of approximately 80 min in
      duration. METHODS: Fourteen active, but not well-trained, male subjects initially
      performed 10 sets of either 5 or 6 x 6 s maximal bike sprints, with varying
      recoveries (24, 54, or 84 s between sprints) over a period of 80 min. Work done
      (kJ) and peak power (W) were recorded for each sprint, and venous blood was
      collected preexercise and on four occasions during the exercise challenge. Muscle
      biopsies (vastus lateralis) were obtained preexercise as well as 0 min and 3 min
      postexercise. Subjects were then administered either 20 g.d-1 Cr.H2O (N = 7) or
      placebo (N = 7) for 5 d. Urine samples were collected for each 24 h of the
      supplementation period. Subjects were then retested using the same procedures as
      in test 1. RESULTS: Total work done increased significantly (P < 0.05) from 251.7
      +/- 18.4 kJ presupplementation to 266.9 +/- 19.3 kJ (6% increase) after Cr
      ingestion. No change was observed for the placebo group (254.0 +/- 10.4 kJ to
      252.3 +/- 9.3 kJ). Work done also improved significantly (P < 0.05) during 6 x 6
      s sets with 54-s and 84-s recoveries and approached significance (P = 0.052) in 5
      x 6 s sets with 24-s recovery in the Cr condition. Peak power was significantly
      increased (P < 0.05) in all types of exercise sets after Cr loading. No
      differences were observed for any performance variables in the placebo group.
      Resting muscle Cr and PCr concentrations were significantly elevated (P < 0.05)
      after 5 d of Cr supplementation (Cr: 48.9%; PCr: 12.5%). Phosphocreatine levels
      were also significantly higher (P < 0.05) immediately and 3 min after the
      completion of exercise in the Cr condition. CONCLUSION: The results of this study
      indicate that Cr ingestion (20 g.day-1 x 5 d) improved exercise performance
      during 80 min of repeated-sprint exercise, possibly due to an increased TCr store
      and improved PCr replenishment rate.

PMID- 11323555
TI  - Little effect of caffeine ingestion on repeated sprints in team-sport athletes.
AB  - PURPOSE: The effect of caffeine ingestion on sprint performance is unclear. We
      have therefore investigated its effect on performance in a test that simulates
      the repeated sprints of team sports. METHODS: In a randomized double-blind
      crossover experiment, 16 male team-sport athletes ingested either caffeine (6
      mg.kg-1 of body mass) or a placebo 60 min before performing a repeated 20-m
      sprint test. The test consisted of 10 sprints, each performed within 10 s and
      followed by rest for the remainder of each 10 s. The caffeine and placebo trials
      followed a familiarization trial, and the time between consecutive trials was 2-3
      d. To allow estimation of variation in treatment effects between individuals,
      nine subjects performed three more trials without a supplement 7-14 d later. We
      estimated the smallest worthwhile effect on sprint time in a team sport to be
      approximately 0.8%. RESULTS: Mean time to complete 10 sprints increased by 0.1%
      (95% likely range -1.5 to 1.7%) with caffeine ingestion relative to placebo.
      Individual variation in this effect was a standard deviation of 0.7% (-2.7 to
      2.9%). Time to complete the 10th sprint was 14.4% longer than the first; caffeine
      increased this time by 0.7% (-1.8 to 3.2%) relative to placebo, and individual
      variation in this effect was 2.4% (-3.4 to 4.9%). CONCLUSION: The observed effect
      of caffeine ingestion on mean sprint performance and fatigue over 10 sprints was
      negligible. The true effect on mean performance could be small at most, although
      the true effects on fatigue and on the performance of individuals could be
      somewhat larger. Pending confirmatory research, team-sport athletes should not
      expect caffeine to enhance sprint performance.

PMID- 11323556
TI  - Association between vitamin E and enhanced athletic performance in sled dogs.
AB  - PURPOSE: To determine the association between prerace plasma vitamin E
      concentration and performance in sled dogs competing in the 1998 Iditarod Race.
      METHODS: Prerace blood samples were collected from 670 dogs. Samples were
      analyzed for plasma vitamin E concentration while controlling for selected
      hematological and biochemical variables and signalment. Starting in teams of 16,
      exercise consisted of running up to 1159 miles pulling a laden sled and musher
      via checkpoints. The records of dogs that were withdrawn from the race for health
      reasons, fatigue, or strategic or technical reasons, and those of dogs that
      finished the race were analyzed. Multiple logistic regression and Cox
      proportional hazards analysis were used to determine factors associated with
      endurance. Multiple linear regression analysis was used to determine factors
      associated with team speed. RESULTS: A total of 323 dogs (48%) were withdrawn
      from racing at various distances from the start. Median time to finish for 39
      teams was 11.5 d and the winning time was 9.2 d. Dogs with prerace plasma vitamin
      E concentrations > 40.7 microg.mL-1 were 1.9 times more likely to finish (P =
      0.0006) and had 1.8 times less of a risk of being withdrawn for every mile ran (P
      = 0.03) than were dogs with plasma vitamin E concentrations between 16.3 and 40.7
      microg.mL-1. Neither a team's mean prerace vitamin E concentration, nor the
      proportion of dogs within a team with high (> 40.7 microg.mL-1) vitamin E
      concentration was associated with team speed. CONCLUSIONS: Dogs with higher
      plasma vitamin E concentrations have enhanced endurance compared with dogs with
      lower plasma vitamin E concentrations, but the plasma vitamin E status of a team
      is not associated with team speed.

PMID- 11323557
TI  - Energy cost of activity assessed by indirect calorimetry and a 13CO2 breath test.
AB  - PURPOSE: The aim of this study was to assess the accuracy of a 13CO2 breath test
      for the prediction of short-duration energy expenditure. METHODS: Eight healthy
      volunteers walked at 1.5 km.h-1 for 60 min followed by 60-min recovery. During
      this time, the energy cost of physical activity was measured via respiratory
      calorimetry and a 13C bicarbonate breath test. A further eight subjects were
      tested using the same two methods during a 60-min cycle at 0.5 kp, 30 rpm
      followed by a 60-min recovery. The rate of appearance of 13CO2 (RaCO2) was
      measured and the mean ratio, VCO2/RaCO2, was used to calculate energy expenditure
      using the isotopic approach. RESULTS: As would be expected, there was a
      significant difference in the energy cost of walking and cycling using both
      methods (P < 0.05). However, no significant differences were observed between
      respiratory calorimetry and the isotope method for measurement of energy
      expenditure while walking or cycling. CONCLUSIONS: These data suggest that the
      13C breath test is a valid method that can be used to measure the energy cost of
      short duration physical activity in a field setting.

PMID- 11323558
TI  - Body composition estimates from multicomponent models using BIA to determine body
      water.
AB  - PURPOSE: The purpose of this study was to compare estimates of body fat (%BF)
      from three- and four-component models with total body water (TBW) determined by
      single-frequency bioelectrical impedance analysis (BIA; %BF3C-BIA and %BF4C-BIA)
      to %BF estimates from densitometry (%BF2C-D) and from three- and four-component
      models with TBW determined using deuterium dilution (%BF3C-D2O and %BF4C-D2O),
      the criterion methods. METHODS: Measures of body density by hydrostatic weighing,
      TBW by BIA and D2O dilution, and bone mineral by dual energy x-ray absorptiometry
      (DXA) were obtained in 40 men and 93 women, 18-42 yr. TBW was estimated from BIA
      resistance (RJL analyzer) using an equation developed and cross-validated in two
      independent samples. Body fat was estimated using the three-component model of
      Siri (1961) and a four-component model modified from Lohman (1986). RESULTS:
      There was a strong relation and no significant difference between TBW estimated
      by BIA and D2O [r = 0.94, SEE = 2.4; xDiff = 0.0 +/- 2.4 L (SD), P > 0.05]. There
      were strong relations between methods for estimating %BF, with deviations from
      %BF4C-D2O (errors) for %BF3C-BIA [r = 0.99, SEE = 2.4% BF, xDiff = -0.4 +/- 2.4%
      BF (SD)] and %BF4C-BIA [r = 0.99, SEE = 2.3% BF, xDiff = 0.2 +/- 2.3% BF (SD)]
      being nonsignificant (P > 0.05) although greater than for %BF3C-D2O [r = 1.00,
      SEE = 0.5% BF, xDiff = -0.6 +/- 0.5% BF (SD)], and comparable or slightly worse
      than for %BF2C-D [r = 0.99, SEE = 2.3% BF, xDiff = 0.4 +/- 2.3% BF (SD)].
      CONCLUSIONS: We conclude that because estimates of %BF from multicomponent models
      with TBW estimated from BIA are not more accurate than from body density alone
      using a two-component model, estimates of %BF from three- and four-component
      models using TBWBIA are not acceptable substitutes for estimates from the same
      models using TBWD2O.

PMID- 11323559
TI  - Sideline preparedness for the team physician: consensus statement.
AB  - The objective of the Sideline Preparedness Statement is to provide physicians who
      are responsible for making decisions regarding the medical care of athletes with
      guidelines for identifying and planning for medical care and services at the site
      of practice or competition. It is not intended as a standard of care and should
      not be interpreted as such. The Sideline Preparedness Statement is only a guide,
      and as such, is of a general nature, consistent with the reasonable, objective
      practice of the health care professional. Individual treatment will turn on the
      specific facts and circumstances presented to the physician at the event.
      Adequate insurance should be in place to help protect the physician, the athlete,
      and the sponsoring organization. The Sideline Preparedness Statement was
      developed by a collaboration of six major professional associations concerned
      about clinical sports medicine issues; they have committed to forming an ongoing
      project-based alliance to bring together sports medicine organizations to best
      serve active people and athletes. The organizations are: American Academy of
      Family Physicians, American Academy of Orthopaedic Surgeons, American College of
      Sports Medicine, American Medical Society for Sports Medicine, American
      Orthopaedic Society for Sports Medicine, and American Osteopathic Academy of
      Sports Medicine.

PMID- 11323560
TI  - Stability of target heart rate values for training.

PMID- 11323562
TI  - [Diagnostic imaging in primary hyperparathyroidism. Radiological techniques: US-
      CAT--MR].
AB  - This study aims to clarify the diagnostic value of ultrasonography, computerised
      tomography and magnetic resonance in adenomatous pathology of primary and
      persistent hyperparathyroidism. Although the diagnostic efficacy of the various
      imaging techniques is still the subject of current debate, the latest specific
      surgical techniques, require their use either individually or in association, in
      order to achieve faster and safer surgery. After an overview of the various
      methods, illustrating their indications and diagnostic limitations, the authors
      emphasise that the role played by ultrasonography, CAT and MR justifies their use
      in the preoperative localisation of parathyroid adenoma. It is not possible to
      assert in absolute terms that one methods is better than another, but each offers
      different potential. The use of US as the method of choice is indicated in
      primary hyperparathyroidism with hyperplastic glands owing to its innocuous
      nature and rapidity. In addition to US and scintigraphy, magnetic resonance may
      be appropriate in primary hyperparathyroidism with adenomatous glands. In
      persistent forms of primary hyperparathyroidism, magnetic resonance is the most
      reliable method, whereas CT and, to an even greater degree, ultrasonography play
      a marginal role.

PMID- 11323563
TI  - [The role of scintigraphy with dual tracer and potassium perchlorate (99mTcO4 &
      KClO4/ MIBI) in primary hyperparathyroidism].
AB  - BACKGROUND: The diagnostic value of scintigraphy using a dual tracer and high
      resolution neck ecotomography in the preoperative localisation of parathyroid
      enlargements was evaluated in a group of consecutive patients suffering from
      primary hyperparathyroidism (HPT) who were uniformly studied and subsequently
      operated by the same surgical team. METHODS: Scintigraphic imaging and high
      resolution neck ecotomography were carried out in a single session on 143
      patients. Scintigraphic imaging was performed using a dual tracer, 99mTc
      pertechnetate/99mTc-MIBI), modified by the addition of potassium perchlorate
      (KCL04) to achieve a rapid washout of 99mTc04 from the thyroid and, consequently,
      to achieve good quality and rapid MIBI images. In a limited number of patients
      (21 cases) SPECT was also performed. Limited surgery was planned in patients with
      evidence of single parathyroid lesions and with normal thyroid parameters, in the
      form of either unilateral or with mini-invasive surgery (91 cases). Patients with
      eco-scintigraphic evidence of multiglandular parathyroid pathology or the
      coexistence of a nodular thyroid goitre, or in patients suffering from MEN or
      familial HPT, or lastly those with negative eco-scintigraphic results under-went
      more extensive surgery with bilateral exploration of the neck (52 cases). A
      single parathyroid lesion was diagnosed during surgery in 90 out of 91 patients
      undergoing planned unilateral or mini-invasive exploration of the neck.
      Therefore, in our experience, the predictive value of preoperative imaging as a
      mean of identifying single parathyroid lesions was 98.9% with a clear impact on
      the choice of conservative surgery. After the removal of the parathyroid to which
      preoperative imaging referred, it was only necessary in one patient to extend
      surgical exploration to the other side of the neck to remove another enlarged
      parathyroid owing to persistent high PTH. RESULTS: The sensitivity of
      scintigraphy and high-resolution neck ecotomography in pa-tients with a single
      adenoma was 94% and 83.7% respectively, whereas it was 76.9% and 64.5%
      respectively in the group of patients with multiglandular pathology. It is worth
      underlining that in all 31 patients with associated nodular thyroid pathology,
      the evaluation of thyroid scintigraphic imaging using 99mTc04 and high-resolution
      neck ecotomography enabled the preoperative diagnosis of thyroid pathology,
      therefore guiding the surgeon towards more extensive surgery. SPECT enabled the
      parathyroid adenoma to be correctly localised in a deep site in 5 patients, in
      the neck in 3 cases and at the mediastinum in 2 patients, providing additional
      data that helped the surgeon to plan surgery. CONCLUSIONS: In conclusion, in our
      experience: a) an integrated diagnostic approach based on scintigraphy 99mTc04 &
      KCLO4/MIBI and high-resolution neck ecotomography was an extremely accurate mean
      of identifying patients with single parathyroid lesions before surgery, enabling
      them to undergo limited surgery, b) scintigraphy with a dual tracer might be the
      elective methods for studying patients with HPT because it allows the
      contemporary diagnosis of possible thyroid diseases. This aspect is extremely
      important in geographical areas with a high predominance of nodular thyroid
      pathology, c) SPECT scintigraphic analysis may be useful in some patients with
      suspected parathyroid adenoma localised in a deep seat, allowing a more precise
      identification of the latter and better surgical planning.

PMID- 11323564
TI  - [Parathyroid carcinoma. Therapeutic strategies derived from 20 years of
      experience].
AB  - BACKGROUND: Carcinoma of the parathyroid is a rare endocrine tumour which can be
      difficult to diagnose even for expert anatomopathologists. METHODS: A
      retrospective study was carried out on all the cases of parathyroid pathology
      observed between January 1980 and October 2000: parathyroid carcinoma was
      diagnosed in 17 (3.59%) out of 478 patients treated for hyperparathyroidism. We
      describe their clinical presentation, treatment and results obtained. The
      patients included 9 women and 8 men, with a male/female ratio of 1.14 and a mean
      age at diagnosis of 56.9 years (range 30-83). All the patients, except one, the
      only non-secreting case, presented hypercalcemia, and 10 patients presented serum
      calcium levels above 3 mmol/L. The symptoms at onset included: nephrolithiasis in
      10 cases, osteoporosis in 4 (3 of which presented uremic syndromes),
      gastrointestinal symptoms (gastritis) in 1 case, a palpable cervical mass in 1
      patient and recurrent nerve palsy in one case suffering from familial IPT. A
      variety of imaging techniques were used for the preoperative localisation: high
      resolution ultrasonography of the neck was carried out in all 17 patients and was
      positive in 15 cases; scintigraphy (99mTcO4/201Tl or 99mO4/MIBI) was carried out
      in 16 patients and was positive in 14; CAT was positive in 6 out of 17 patients.
      Three patients underwent the first operation in another hospital and were
      referred to our department for resistance or recidive. Initial surgery was
      restricted to simple parathyroidectomy in 4 cases; parathyroidectomy was extended
      to the entire gland in 3 patients with uremic syndrome and to the ipsilateral
      thyroid lobe in 7 cases. Three patients underwent parathyroidectomy extended en
      bloc to the adjacent structures, and recurrent lymph node dissection was also
      performed in 2 of these patients. Lymph node involvement was never demonstrated
      during the first operation. The dimensions of the tumour varied from 1 to 6.7 cm;
      we found signs of invasion of the neighbouring structures in 3 patients. RESULTS:
      Parathyroid carcinoma was correctly diagnosed during the first operation in 14
      cases (this diagnosis was suspected in 10 cases following intraoperative frozen
      session), whereas the first diagnosis was of benign disease in 3 patients. Blood
      levels of calcium, phosphorus and PTH returned to normal after the first
      operation in 13 patients. These values diminished, but did not return to normal
      in 2 cases. Two patients relapsed, respectively 5 and 175 months after the first
      operation. A total of 10 reoperations were performed in 4 patients with
      persistent/recurrent symptoms (from a minimum of 1 to a maximum of 4). Recidive
      presented characteristics of local invasiveness in one case and the persistence
      was supported by micro-insemination of the pre-thyroid compartment and muscles in
      another two cases. At reoperation, lymph node metastasis was associated with
      local recidive only in one case. Two patients underwent radiotherapy after
      surgery and one received chemotherapy. At the last check-up (October 2000), 14
      patients were alive and disease-free (82.25%). Two presented slight persistent
      hypercalcemia (with values ranging between 2.65 and 2.80 mmol/L), but without any
      macroscopic localisation of disease (11.76%). Only 1 patient died (5.88%) (one
      year after the first operation and 7 months after the last one). Death was caused
      by uncontrollable hypercalcemia supported by widespread metastasis to the bones
      and lungs. The 5 and 10-year survival rates were calculated as 94.12%.
      CONCLUSIONS: In conclusion, high blood levels of calcium and PTH, a palpable mass
      at the neck, with recurrent nerve paralysis, aspects of local invasiveness should
      alert the surgeon and guide him towards surgery that includes resection of the
      parathyroid en bloc with the adjacent structures, although there is no proof that
      a more extensive surgery is correlated with a more favourable prognosis. Being
      the majority of recidive functional, monitoring serum calcium and PTH levels
      offers a useful market which precedes their macroscopic demonstration.

PMID- 11323565
TI  - [Primary hyperparathyroidism in patients treated for non-medullary thyroid
      carcinoma].
AB  - The authors report three cases of primary hyperparathyroidism (HPT) in patients
      with differentiated thyroid carcinoma (DTC) developed a few years after initial
      surgical and radiometabolic treatment of DTC. The early diagnosis of HPT in these
      patients was made possible because of laboratory tests performed during follow
      up, including the assay of serum calcium and serum phosphorus levels. Scinti
      graphy using 99mTc-MIBI enabled the correct preoperative localisation of a single
      parathyroid adenoma in two of these patients and multiglandular pathology in the
      third.

PMID- 11323566
TI  - [Radio-guided parathyroidectomy. A prospective study in 54 patients with primary
      hyperparathyroidism].
AB  - BACKGROUND: The contribution of nuclear-medical mapping using 99mTc-MIBI (MIBI)
      and the use of an intraoperative probe in primary hyperparathyroidism (I degrees
      HPT) surgery was evaluated prospectively in a series of patients undergoing
      parathyroidectomy. METHODS: Fifty-four patients, who were operated between May
      1999 and July 2000, under-went a systematic preoperative evaluation using
      scintigraphy with a dual tracer 99Tc04/MIBI and image subtraction, and high
      resolution neck ecotomography. Surgery was performed using a mini-invasive
      technique through an incision measuring 2-2.5 cm at the base of the neck in 46
      patients; the other 8 patients underwent open surgery with bilateral exploration
      of the neck. MIBI was injected intravenously in the operating theatre following
      the induction of anesthesia and after 32 minutes on average, radioactivity was
      measured using a manual gamma probe. Radioactivity was also counted
      intraoperatively at the tip of the lung contralateral to the pathological gland,
      a parameter used as the base activity (B), in the presumed seat of the
      hyperfunctioning parathyroid (P), in correspondence with healthy thyroid tissue
      (T) and any associated thyroid nodes (N). Radioactivity was also recorded at the
      level of the  empty  parathyroid compartment after removal of the corresponding
      gland, and on the parathyroid removed  ex vivo . RESULTS: The ratio between the
      three main parameters, T/B, P/B and P/T was respectively 1.6 (range=1.5 - 1.8),
      2.7 (range=1.6-4.0) and 1.6 (range=1.1-2.8). In 4 cases (7.4%), the small size of
      the parathyroids, adjacent to thyroid nodes, meant that the parathyroid
      measurement of MIBI was smaller than the thyroid measurement. The histological
      finding was consistent with: single parathyroid adenoma in 49 cases, multiple
      adenomas in 3 cases, parathyroid carcinoma in 2 cases. Rapid intraoperative PTH
      normalised in all patients. CONCLUSIONS: The significant difference in
      radioactivity levels recorded in the patients, showed that the technique is
      useful to the surgeon as a means of intraoperative assay for hyperfunctioning
      parathyroids, even if it cannot obviously replace experience or the value of
      preoperative scientigraphic and ecotomographic imaging.

PMID- 11323567
TI  - New hematological indices in the healthy elderly.
AB  - BACKGROUND: Recently, new indices related to erythrocytes and platelet counts
      have been provided by hematological analysers. The purpose of the study is to
      investigate these new parameters in the elderly to define their normal values and
      to compare them with the range provided by the manufacturer. METHODS: 
      EXPERIMENTAL DESIGN: a comparative study. SETTING: general community, geriatric
      and internal medicine ambulatories. PATIENTS: sixty healthy free-living elderly
      (cut-off: 65 years) and 66 healthy young-adults, as a control group. MEASURES: we
      measured the common and the new hematological parameters by H.1 Bayer technology.
      The new hematological parameters are red diameter width-RDW, hemoglobin
      distribution width-HDW, mean platelet volume-MPV, platelet diameter width-PDW,
      platelet hematocrit-Pct. We then compared the values of our population with the
      Bayer range. RESULTS: The confidence interval width of the new indices define
      very faster limits than the Bayer range. Statistical differences were significant
      only in male groups: young-adults (Y) versus elderly (E) with higher values in Y
      than E in RBC p=0.002, in Platelet count p=0.050 and in MPV p=0.026; and higher
      values in E in MCV p=0.008, MCH p=0.006 and PDW p=0.004. CONCLUSIONS: In the
      literature a wide range of common hematological parameters are reported in the
      elderly, while the new hematological values have not been discussed till now. Our
      results may contribute to define the laboratory limits of the new hematological
      values in the healthy elderly.

PMID- 11323568
TI  - [The longevity of centenarians].
AB  - BACKGROUND: The increase of mean lifetime has also given rise to an increase in
      the number of centenarians; such a circumstance finds its explanation in an
      improvement in hygienic conditions in addition to the progress in the medical
      field. The aim of this retrospective study is the attempt to identify the
      probable factors encouraging the achievement of an extreme longevity. METHODS:
      The study was carried out, on a house to house basis, on a sample of 46 calabrian
      centenarians. In order to demonstrate the hereditary component, the frequency of
      the centenarians among the closest relatives was considered, through birth and
      death certificates. The case history questionnaire used most geriatric and
      gerontological centres associated to the national project  Italian Multicentric
      Study on Centena-rians  was used. RESULTS: The profile of our long-lived subject
      has allowed us to underline the importance of the environmental factor as well as
      the hereditary component. In most cases these subjects live with their family and
      have excellent relationships, receiving a great deal of attention from the
      persons with which they live. CONCLUSIONS: The authors have therefore reached the
      conclusion by stressing the importance of both factors (hereditary and genetic);
      however a type of intervention in order to lengthen the mean lifetime is
      hypothesized exclusively in the environment field through the elimination of
      certain risk factors.

PMID- 11323569
TI  - [Gastroenterologists in ambulatory care. The experience in Turin in the year
      2000].
AB  - BACKGROUND: Digestive diseases (GI) have a major impact on public health in
      Italy. Hospital stay for digestive pathologies parallels that due to
      cardiovascular causes. Total mortality for GI causes is also very high. The
      management of GI pathologies is therefore a major task for the National Health
      System. To the experienced gastroenterologist it is clear that a large number of
      hospitalisation is linked to a lack of careful outpatient follow-up of diseases
      such as cirrhosis, ulcerative colitis and peptic ulcer. METHODS: One year of
      activity of our Gastro-entero-Hepatology outpatient service is examined. The
      management of the majority of GI diseases is organized in  working teams  of
      physicians and surgeons following cohorts of patients suffering of a specific
      disease. RESULTS: During the year 2000 not only a statistically significant
      higher number of patients has been examined (p<0.05), in comparison with 1994,
      but also the hospitalisation rate was lowered resulting in a very significative
      cost-containment. CONCLUSIONS: The specialization of outpatient activities into 
      working teams  offers advantages in terms of more appropriate medical care and
      cost reduction, partly due to a less frequent hospitalisation. The obvious
      counterpart was an increase of request of such form of follow-up from patients,
      resulting in longer delay to the access.

PMID- 11323570
TI  - [Importance of dermatologic screening within the frame work of a general cancer
      prevention program].
AB  - BACKGROUND: Skin tumours represent about 11% of all the malignant neoplasms and
      their frequency is increasing annually. Skin tumours (melanoma, basal and
      squamous cell carcinoma, etc.) can be used for a good screening activity, but in
      relation to breast or cervix uteri cancer needs to be better defined. A test on a
      population of selected patients against skin malignant neoplasms has been carried
      out in our Centre. All of them had skin lesions and further checks were
      necessary. METHODS: The diagnostic protocol used in our Centre for Oncological
      Prevention uses the collection of anamnestic data and an objective examination.
      Between 1996 and 2000, 222 patients between the ages of 18 and 80 have been
      selected. All of them had suspected skin lesions. The patients were selected by
      the oncologist, particularly for pigmentation, asymmetry, irregular borders and
      heterogeneous colour of their skin lesions. Subsequently, the patients were sent
      for a further examination to the dermatologist oncologist, who on the basis of
      the objective dermatological examination with possible dermatoscopy, made a
      clinical diagnosis of the skin injuries or suggested surgical removal for the
      histological control of the same. RESULTS: Requested consultations: 222. Exami
      nations made: 195. Patients considered: 190. Skin injuries examined: 190. The
      following skin lesions were identified: melanoma: 4 (2.1%) [2: I Clark level; 2:
      II Clark level]; basal cell carcinoma: 14 (7.37%); dermatofibrosarcoma: 1
      (0.53%); keratoacanthoma: 1 (0.53%); dysplastic nevus: 4 (2.1%); actinic
      keratosis: 7 (3.68%); benign lesions: 159 (83.68%). CONCLUSIONS: These data were
      obtained by a screening program and it is therefore not a random study. This
      study shows interesting results because tumoral skin lesions and in particular
      melanoma were recognised at early stages. This is more than enough for us to
      create a specific screening program for skin lesions to cut down the rate of
      morbidity and mortality.

PMID- 11323571
TI  - [Neurofibromatosis (NF1) and neuroleprosy: immunoreaction against pathologic
      Schwann-cells. Physiopathogenetic observations].
AB  - BACKGROUND: We reviewed the literature evaluating the immune reaction in
      neurofibromatosis (NF1) and neuroleprosy, so as to underline the
      immunopathegenetic parallelism and the possible therapeutic implications
      regarding the treatment of these two disorders. In particular we evaluated the
      systemic modifications and the local fibrotic events that lead to nerve damage in
      NF1 and complete neuronal destruction as in leprosy. METHODS: With the above aim
      in mind we studied the histology, histochemistry and immunohistochemistry
      (Schwann cells and immunoglobulins) of four plexiform neurofibroma, one common
      neurofibroma and one case of borderline neuroleprosy (BT). RESULTS: Two plexiform
      neurofibromas showed an evident immune reaction that was antibody mediated with
      numerous IgG; the remaining neurofibromas represented other stages of disease
      evolution and disease quiescence and thus showed a scarce immune reaction with a
      reduced presence of immunoglobulins. All the neurofibromas showed the presence of
      fibrous bundles. In the case of neuroleprosy (BT), the immune reaction was
      modest, immunoglobulins were present and fibrotic transformation on neuronal
      fibers was observed. CONCLUSIONS: Being that pathologic Schwann cell are the site
      of immune reactions that can become abnormal (at times with autoimmune
      reactions), clinical as well as biochemical surveillance of leprous neuropathy
      and NF1 could allow for a timely modification of the abnormal reaction with
      selective immunomodulators. The inactivation of the mycobacterial RNA polymerase
      or of the NF1 gene could offer hope for controlling disease activity and disease
      evolution of the two disorders.

PMID- 11323572
TI  - [The pro-apoptotic factors Fas Ligand and Trail. Molecular mechanisms,
      physiopathological role and therapeutic potential].
AB  - Programmed cell death, also known as apoptosis, is a normal physiologic process
      which occurs during embryonic development as well as in maintenance of tissue
      homeostasis. Increasing evidence suggests that alterations in cell death
      contribute to the pathogenesis of a number of human diseases, including cancer,
      viral infections, autoimmune diseases and acquired immunodeficiency syndrome
      (AIDS). The extraordinary research activity of the past few years has resulted in
      the characterization of the principal proteins involved in the apoptosis
      machinery. An area of particular interest has been the induction of apoptosis by
      two death receptor/ligand pairs, Fas/Fas Ligand and DR4-DR5/TRAIL. The
      identification of these molecules with the recruited signaling pathways could
      clarify their physiopathological implications, having a significant impact upon
      potential therapeutic interventions in diseases associated with cell survival
      alterations.

PMID- 11323573
TI  - Diagnostic criteria of glucose intolerance and mortality.
AB  - In 1997 American Diabetes Association (ADA) Expert Committee approved changing
      the diagnostic criteria for diabetes. The major change is to lower fasting plasma
      glucose from 7.8 mmol/l to 7.0 mmol/l for diabetes and did not recommend the use
      of 2-hour 75 g oral glucose tolerance test (OGTT). The decision by the ADA not to
      recommend the OGTT has been criticised based on the findings of several recent
      studies, in particularly those from the Diabetes Epidemiology: Collaborative
      Analysis of Diagnostic Criteria in Europe (DECODE) and in Asia (DECODA) Studies.
      These studies have reported that only 29% of all newly screened diabetic subjects
      qualified for diabetes on both the fasting and the 2-hour glucose criteria in
      European and 37% in Asian populations. It has now been clearly shown that elderly
      and less obese patients are more likely to have diagnostic 2-hour values, whereas
      fasting hyperglycaemia is more common among obese subjects. Analysis of the
      prospective DECODE data showed that elevated 2-hour glucose was a better
      predictor of mortality from all-cause and from cardiovascular and non
      cardiovascular diseases than elevated fasting glucose alone. The largest absolute
      number of excess deaths was observed in subjects with impaired glucose tolerance
      (IGT), especially in those whose fasting glucose was normal.

PMID- 11323574
TI  - [Systemic sclerosis. Which therapies?].
AB  - Sistemic sclerosis is a connective tissue disease characterized by excessive
      deposit of collagen in the skin and in different viscera such as the lung, the
      heart, the kidney, the gastrointestinal tract and muscoloskeletal system.
      Fibrosis is a natural and not reversible consequence of this extracellular matrix
      accumulation. Past management strategies have not been successful, usually. New
      physiopathologic knowledges establish the bases to obtain a more successful
      control of the disease evolution. Literature data underline the importance of a
      timely and personalized therapy based on kind, seriousness and stage of internal
      organs involvement to allow the patient to continue normal public relations, a
      good quality of life and the improvement of its global prognosis of this disease,
      often cause of disability and death. Actually, drug therapeutic management is
      based on combined use of vascular drugs: topical (Nitroglycerin patches), oral
      (Ace inhibitors and Calcium channel blockers) or, in severe cases, parenteral
      vasodilators (Prostaglandins and Prostacyclins), immunosuppressive therapies
      (Cyclophosphamide, Cyclosporin A, Methotrexate) and antifibrotic drugs (Penicil
      lamine, Interferons).

PMID- 11323575
TI  - [Monitoring of primary cerebral injury due to trauma].
AB  - The author analyses and synthetizes the standard parameters of monitoring the
      evolutive cerebral injury after cranial trauma. This study presents the main
      criteria and the reciprocal relation between parameters in the prognostic
      function.

PMID- 11323576
TI  - [Renal involvement in Waldenstroms macroglobulinemia. Case report and review of
      the literature].
AB  - The author reports a patient with Waldenstroms macroglobulinemia and infiltration
      of the kidney interstitium with lymphoplasmacytoid cells. In contrast to multiple
      myeloma, infiltration of the kidney interstitium with lymphoplasmacytoid cells is
      not a rare event in Waldenstrom s macroglobulinemia at all. Our case reported
      showed enlargement of the kidney with a diffuse increase in the cortical
      echogenicity and the presence of hypoechogenic areas scattered throughout the
      kidney, there was no renal or perirenal masses. The treatment with chlorambucil
      and prednisone was ineffective, and she has a good response to a polychemotherapy
      regimen. The role of fine-needle aspiration biopsy performed under ultrasound
      guidance is emphasized.

PMID- 11323577
TI  - Unilateral versus bilateral endoscopic hepatic duct drainage in patients with
      malignant hilar biliary obstruction: results of a prospective, randomized, and
      controlled study.
AB  - BACKGROUND: The necessity for drainage of both liver lobes in tumors arising at
      the biliary bifurcation is controversial. The aim of this study was to compare
      the outcome of unilateral versus bilateral drainage in patients with biliary
      obstruction at the hilum. METHODS: One hundred fifty-seven consecutive patients
      with primary cholangiocarcinoma, gallbladder cancer, or periportal lymph node
      metastases were randomly allocated to unilateral (group A) or bilateral (group B)
      hepatic duct drainage. RESULTS: In intention-to treat analysis, group A had a
      significantly higher rate of successful endoscopic stent insertion than group B
      (88.6% vs. 76.9%, p = 0.041). Group B had a significantly higher rate of
      complications than group A (26.9% vs. 18.9%, p = 0.026) because of the higher
      rate of early cholangitis (16.6% vs. 8.8%, p = 0.013). In per-protocol analysis
      the rate of successful drainage, complications, and mortality did not differ
      between the two groups. Median survival did not differ between the two groups but
      was significantly different for patients with cholangiocarcinoma and those with
      gallbladder cancer versus patients with metastatic tumors (p = 0.0247).
      CONCLUSION: The insertion of more than one stent would not appear justified as a
      routine procedure in patients with biliary bifurcation tumors.

PMID- 11323578
TI  - Effective and safe endoscopic reversal of nondysplastic Barrett's esophagus with
      thermal electrocoagulation combined with high-dose acid inhibition: a multicenter
      study.
AB  - BACKGROUND: Barrett's esophagus is a metaplastic change in the esophageal lining
      with an increased risk for adenocarcinoma. Multiple endoscopic techniques have
      been applied in an effort to reverse Barrett's. This is a multicenter trial
      defining the efficacy and safety of multipolar electrocoagulation combined with
      high-dose acid inhibition. METHODS: Patients with a 2- to 6-cm segment of
      Barrett's esophagus without dysplasia were enrolled at 3 centers. They were
      treated with omeprazole 40 mg twice daily and then with up to 6 sessions with
      electrocoagulation aimed at eliminating all the endoscopically apparent
      Barrett's. Four quadrant large-capacity biopsies every 2 cm were centrally
      assessed for residual intestinal metaplasia. RESULTS: Fifty-eight patients
      reached the endpoint of failure of visual reversal of Barrett's after 6 treatment
      sessions or a 6-month follow-up after the last session. Eighty-five percent had
      visual reversal and 78% both visual and histologic reversal. Four patients had
      histologic evidence of residual intestinal metaplasia. Transient esophageal
      symptoms were common. One patient developed a stricture requiring dilation and
      one required overnight hospitalization for chest pain. CONCLUSIONS: The majority
      of patients with 2 to 6 cm of nondysplastic Barrett's esophagus can be safely
      reversed with this combination therapy. Long-term follow-up will be necessary to
      document the durability of the new squamous epithelium.

PMID- 11323579
TI  - Enhanced magnification endoscopy: a new technique to identify specialized
      intestinal metaplasia in Barrett's esophagus.
AB  - BACKGROUND: Specialized intestinal metaplasia (SIM) in Barrett's esophagus (BE)
      is not identifiable by standard endoscopy. Acetic acid instillation enhances the
      ability to detect columnar epithelium at the squamocolumnar union. Enhanced
      magnification endoscopy involves the combined use of magnification endoscopy with
      acetic acid. This study assessed the value of enhanced magnification endoscopy in
      detecting SIM in patients with BE. METHODS: Patients undergoing endoscopic
      surveillance because of short segment BE without dysplasia underwent enhanced
      magnification endoscopy with 1.5% acetic acid instillation. Standard endoscopy
      was followed by magnification endoscopy and repeated after acetic acid spraying.
      Surface patterns were characterized prior to and after acetic acid spraying. The
      observed surface patterns were compared with histology results. RESULTS: Forty
      nine patients, 9 women and 39 men, with a mean age of 50.5 years were studied.
      One was excluded because of unclear definition of the surface pattern. Enhanced
      magnification endoscopy detected 4 different mucosal surface patterns: I, round
      pits; II, reticular; III, villous; and IV, ridged. A total of 129 areas were
      examined. Standard endoscopy identified an endoscopic pattern in 1.5% of the
      areas, standard endoscopy and acetic acid in 8.5%, magnification endoscopy alone
      in 38%, and enhanced magnification endoscopy in all 129 endoscopic areas. The
      yields for detecting SIM according to endoscopic patterns were as follows:
      pattern I, 0%; II, 11% (odds ratio 0.5, p = 0.54); III, 87% (odds ratio 36, p =
      0.001); and IV, 100% (odds ratio 14, p = 0.015). CONCLUSIONS: Enhanced
      magnification endoscopy is an accurate method of predicting SIM in BE. The
      simplicity of the technique and its ability to identify characteristic endoscopic
      patterns with outstanding clarity and resolution that correlate with histologic
      identification of specialized intestinal metaplasia make enhanced magnification
      endoscopy an excellent method for the evaluation of patients with BE.

PMID- 11323580
TI  - Adjuvant sclerotherapy after ligation for the treatment of esophageal varices: a
      prospective, randomized long-term study.
AB  - BACKGROUND: To assess the efficacy of adjuvant sclerotherapy after banding for
      the treatment of esophageal varices, a randomized trial was carried out of
      endoscopic variceal ligation (EVL) alone with sequential sclerotherapy versus
      sequential ligation-sclerotherapy (SLS) after banding with respect to variceal
      eradication, associated complications, and recurrence of varices. METHODS: One
      hundred patients qualified for this study. Fourteen patients were not included
      for the following reasons: 6 chose not to participate, 4 had fundal varices, and
      4 had some form of cancer. Of the remaining 86 patients in the study, 42
      underwent EVL alone and the other 44 SLS. Variceal ligation was begun in the
      region of the gastroesophageal junction, with subsequent ligatures applied
      cephalad 3 to 5 cm; ligation was repeated every 2 weeks until variceal
      obliteration. For SLS, ligation was also begun in the region of the
      gastroesophageal junction and repeated until varices were reduced to F1 size.
      Subsequently, these patients underwent sclerotherapy with between 6 and 8 mL of
      sodium tetradecyl sulfate (free hand technique). RESULTS: No significant
      differences were found between EVL alone and SLS with regard to variceal
      eradication, development of associated complications, and recurrent bleeding
      during a follow-up of 2 years. The probability of variceal recurrence requiring
      further treatment after 1 year was 14% for the SLS group and 26% for EVL group
      patients. Another year later, the probability of variceal recurrence was 24% and
      45%, respectively, for the SLS and EVL groups. CONCLUSIONS: Because a
      significantly lower rate of variceal recurrence was found for SLS patients,
      sequential sclerotherapy followed by ligation to eradicate those varices too
      small to easily band may be a better procedure.

PMID- 11323581
TI  - A new "sandwich" method of combined endoscopic variceal ligation and
      sclerotherapy versus ligation alone in the treatment of esophageal variceal
      bleeding: a randomized trial.
AB  - BACKGROUND: Variceal ligation is the optimum endoscopic method for treating
      esophageal variceal bleeding. However, both early and multiple recurrences of
      esophageal varices frequently follow ligation. The aim of this randomized study
      was to determine whether a new, combined endoscopic "sandwich" method (i.e.,
      ligation-sclerotherapy-ligation) could achieve better results than ligation
      alone. METHODS: Ninety-four patients with cirrhosis and acute or recent
      esophageal variceal bleeding were randomized to undergo either the "sandwich"
      method or ligation alone (47 patients in each group). RESULTS: The sclerosant was
      retained in the varices for more than 30 minutes in 7 of 8 patients undergoing
      the "sandwich" method plus radiographic contrast medium. Active bleeding was
      controlled with this new method (9/9) as efficiently as ligation (12/12). The
      rate of recurrent bleeding was similar for both methods. Multivariate analysis
      showed the necessity for the use of antibiotics (odds ratio 3.95: 95% CI [1.60,
      9.76]) to be an independent factor for recurrent bleeding. Two patients in the
      "sandwich" group developed strictures, but the frequency of other complications
      did not differ between the 2 groups. Kaplan-Meier analysis showed the cumulative
      probability of variceal recurrence was lower with the "sandwich" method (p =
      0.0391). The survival rate and causes of death were similar in both groups.
      CONCLUSIONS: The "sandwich" method leads to longer retention of sclerosant in
      varices. This method is superior to ligation alone in terms of lower variceal
      recurrence rate and comparable to ligation with respect to hemostasis. However,
      it is unknown whether the lower recurrence rate of varices will persist long
      term.

PMID- 11323582
TI  - The effects of endoscopic variceal ligation and propranolol on portal
      hypertensive gastropathy: a prospective, controlled trial.
AB  - BACKGROUND: Endoscopic treatment of esophageal varices may accentuate portal
      hypertensive gastropathy. The impact of the combination of band ligation and
      propranolol on this condition remains unknown. METHODS: Patients with history of
      variceal bleeding were randomized to receive band ligation alone (control group,
      40 patients) or a combination of band ligation and propranolol (propranolol
      group, 37 patients). Serial endoscopic evaluation of gastropathy was performed.
      Gastropathy was classified into 3 grades and scored as 0, 1, or 2. RESULTS:
      Before endoscopic treatment, 17% of the control group and 22% of the propranolol
      group had gastropathy (p = 0.78). The occurrence of gastropathy after endoscopic
      treatment was significantly higher in the control group than in the propranolol
      group (p = 0.002). Serial endoscopic follow-up revealed that the mean gastropathy
      score was significantly higher in the control group than in the propranolol group
      (p < 0.05). In patients with gastropathy the gastropathy score reached a peak at
      6 months after endoscopic treatment in both the control and propranolol groups
      (85% vs. 48%, respectively). After variceal obliteration, accentuation of
      gastropathy was significant in the control group (p < 0.01) but not in the
      propranolol group. Gastropathy was less likely to develop in patients who
      developed gastric varices. Esophageal variceal recurrence was not related to the
      development of gastropathy after variceal obliteration with banding. Only one
      patient in the control group bled from gastropathy. CONCLUSION: Band ligation of
      esophageal varices may accentuate gastropathy, which in this study was partly
      relieved by propranolol.

PMID- 11323583
TI  - Endoscopic ablation with cyanoacrylate glue for isolated gastric variceal
      bleeding.
AB  - BACKGROUND: Endoscopic ablation with cyanoacrylate glue may achieve gastric
      variceal obliteration. A prospective evaluation of its therapeutic effects on
      bleeding gastric varices was conducted, focusing on endoscopic features. METHODS:
      Thirty-seven patients with bleeding gastric varices underwent endoscopic ablation
      with cyanoacrylate. RESULTS: Patients with localized-type gastric varices (n =
      14) had a better clinical course in terms of recurrent bleeding, variceal
      eradication, and survival than those with diffuse-type gastric varices (n = 23)
      after endoscopic ablation with cyanoacrylate. These clinical effects were related
      to the vascular anatomy of the gastric varices as determined by varicography and
      3-dimensional CT. Type 1 vascular anatomy (one varicose vessel without noticeable
      ramifications) was much more common (86%) in localized-type gastric varices,
      whereas type 2 vascular anatomy (multiple varicose vessels with complex
      connecting ramifications) was found almost exclusively (91%) in diffuse-type
      gastric varices. CONCLUSIONS: Endoscopic ablation with cyanoacrylate is an
      effective and safe procedure for patients with bleeding gastric varices.
      Determination of variceal anatomy may be useful for improving treatment
      strategies for such patients.

PMID- 11323584
TI  - EUS in patients with benign and malignant lymphadenopathy.
AB  - BACKGROUND: The EUS appearance of lymph nodes in patients undergoing evaluation
      for malignancy was studied. METHODS: In 378 patients EUS characteristics were
      assessed: size of tumor, largest lymph node size, number of lymph nodes, distance
      of lymph nodes from the tumor, and on a 5-point visual analogue scale (1 = least
      malignant to 5 = most malignant), roundness, homogeneity, and echogenicity. A
      morphology score (sum of roundness, homogeneity, and echogenicity) was
      calculated. Findings were compared with fine needle aspiration or surgical
      histopathology in 238 patients. RESULTS: When using multivariate analysis, only
      lymph node size (1.4 +/- 0.1 cm vs. 1.7 +/- 0.1 cm, p = 0.001), distance from
      tumor (3.1 +/- 0.4 cm vs. 1.6 +/- 0.4 cm, p = 0.013), and morphology score (9.9
      +/- 0.3 vs. 11.9 +/- 0.3, p = 0.001) for benign versus malignant lymph nodes
      (mean +/- SEM) were significant. Lymph node size was significant for esophageal
      cancer (p = 0.006) and other mediastinal lymph nodes (p = 0.007) but not for
      pancreaticobiliary malignancies (p = 0.1) or celiac lymph nodes (p = 0.4).
      Distance from the tumor was significant for pancreaticobiliary (p = 0.01) but not
      esophageal cancers (p = 0.7). Morphology was significant for all sites. The
      presence of at least one lymph node of 1 cm or greater within 1 cm of the tumor
      and with a morphology score of 14 or greater had a positive predictive value of
      81% (prevalence = 13%). A morphology score of 6 or less had a negative predictive
      value of 92% (prevalence = 12%). CONCLUSIONS: Patients with malignant adenopathy
      have lymph nodes that are larger, closer to the primary tumor, rounder, darker,
      and more homogeneous than those of patients without malignant adenopathy.

PMID- 11323585
TI  - Cervical esophageal perforation during EUS: a national survey.
AB  - BACKGROUND: EUS is considered to be as safe a procedure as EGD. However, the
      longer, rigid tip of the echoendoscopes raises concern about cervical esophageal
      perforation during intubation. Our aim was to determine the rate of this
      complication. METHODS: Members of the American Endosonography Club were surveyed
      by questionnaire to determine the number of EUS examinations performed and the
      number of cervical esophageal perforations encountered up to June 1999. Each
      questionnaire was coded to avoid duplicate reporting. RESULTS: Questionnaires
      were mailed to 203 members; 86 (42.4%) responded. Cervical esophageal perforation
      occurred in 16 of 43,852 reported upper EUS procedures at a frequency of 0.03%.
      Fifteen (94%) patients were elderly. A history of difficult intubation with prior
      endoscopic procedures was present in 7 (44%) patients. Three patients had large
      cervical osteophytes. In 9 (56%) patients, the procedure was done by an
      endosonographer with less than 1 year of experience. Two patients required
      surgery. One patient died as a result of the perforation and the other 13 (81%)
      patients were managed successfully with conservative treatment. CONCLUSIONS: The
      incidence of cervical perforation during upper EUS may be higher than during EGD.
      Advanced patient age, difficult intubation during prior upper endoscopy, operator
      inexperience, and the presence of large cervical osteophytes may contribute to
      cervical perforation during upper EUS examination.

PMID- 11323586
TI  - Self-expanding metal esophageal stent with anti-reflux mechanism.
AB  - BACKGROUND: When deployed across the gastroesophageal junction, self-expanding
      metal esophageal stents can predispose to gastroesophageal reflux. Our aim was to
      evaluate the efficacy of a self-expanding metal esophageal stent that was
      modified to prevent gastroesophageal reflux. METHODS: The polyurethane coating of
      a metal Z-stent was extended beyond its lower end to form windsock-type valve.
      The anti-reflux property of this stent was studied in vitro by submerging the
      stent under water and measuring the pressure required to invert the valve.
      Esophageal acid exposure time was measured in 5 dogs with a standard and the
      modified stent placed across the gastroesophageal junction. The modified stent
      was also placed in 11 patients with cancer of the gastroesophageal junction who
      were prospectively followed. RESULTS: The pressure required to invert the valve
      was directly proportional to the thickness of the valve membrane (48 +/- 0.4 cm
      water for a 0.0067-inch thick membrane). Esophageal acid exposure time was
      significantly less with the modified stent as compared with a standard stent (1%
      +/- 0.3%, 49% +/- 11%, respectively, p = 0.03). Dysphagia score in patients
      improved from 3.4 +/- 0.1 to 1.1 +/- 0.2 (p < 0.001). Daytime heartburn and
      regurgitation scores were less than 1 (score 10 = severe). No patient complained
      of nocturnal reflux symptoms. Karnofsky performance status scale did not improve
      significantly. CONCLUSIONS: The efficacy of the modified stent in relieving
      dysphagia is comparable with a standard stent. It also effectively prevents
      gastroesophageal reflux.

PMID- 11323587
TI  - Pancreaticobiliary maljunction: etiologic concepts based on radiologic aspects.
AB  - BACKGROUND: The purpose of this study was to develop a new concept of the
      embryonic etiology of pancreaticobiliary maljunction (PBM) based on
      cholangiopancreatograms. METHODS: The subjects were 202 patients with PBM (60 men
      and 142 women) in whom the junction of the pancreatic and bile ducts was
      radiologically diagnosed as being located outside of the duodenal wall; 133 of
      the 202 patients also had congenital cystic dilatation of the bile duct (CCBD).
      RESULTS: The length of the duct from the junction to the orifice of the major
      papilla (the common channel) ranged from 0.5 to 5 cm on the
      cholangiopancreatograms. Small radicles of the pancreatic duct arose from the
      common channel in 36 of the 202 patients. This finding suggests that the common
      channel is itself the main pancreatic duct in patients with PBM. Moreover,
      cholangiopancreatography revealed that in 99 of the 202 patients, there was a
      narrowed duct segment distal to the biliary cyst in patients with CCBD or distal
      to the normal bile duct in those without CCBD; the length of the narrowed segment
      varied. Histologic examination revealed smaller branches that had arisen from
      this narrowed segment in 2 anatomic specimens. This also suggests that the
      narrowed ductal segment belongs to the pancreatic duct system. CONCLUSION: PBM is
      an anomaly that is probably caused by a disturbance in the embryologic
      connections (misarrangement) of the pancreatic and biliary duct system that
      occurs extremely early during gestation when the bile duct joins with the ventral
      pancreatic duct system. PBM is not due to an arrest of the normal migration of
      the common channel into the duodenal lumen during embryonic development.

PMID- 11323588
TI  - Prospective evaluation of complications in outpatient GI endoscopy: a survey
      among German gastroenterologists.
AB  - BACKGROUND: Although most diagnostic GI endoscopic procedures in Germany are
      performed on an outpatient basis, there is no large-scale prospective evaluation
      of complication rates. METHODS: Ninety-four gastroenterologists and internists
      from all regions of Germany recorded the number of EGD, colonoscopies, and
      polypectomies performed over a period of 1 year. All serious complications
      occurring in relation to the procedure, including the use of medication, were
      recorded in a structured protocol. RESULTS: A total of 110,469 EGDs, 82,416
      colonoscopies, and 14,249 polypectomies were evaluated. The "reach-the-cecum
      rate" was 97% (median). The overall complication rates for EGD, colonoscopy, and
      polypectomy were low compared with published data (0.009%, 0.02%, and 0.36%,
      respectively). The perforation rates were 0.0009%, 0.005%, and 0.06%,
      respectively, the rates of significant hemorrhage 0.002%, 0.001%, and 0.26%,
      respectively, and the mortality rates 0.0009%, 0.001%, and 0.007%, respectively.
      The rates of cardiorespiratory complications associated with EGD and colonoscopy
      were 0.005% and 0.01%, respectively. The overall complication rate for all
      procedures (diagnostic and therapeutic) was lower for gastroenterologists (1 per
      5155 procedures) than internists (1 per 1539 procedures). Most of the adverse
      events associated with diagnostic endoscopy were attributable to use of
      medication. The severity score ranged from 2 to 5 for most of the adverse events
      occurring as a result of diagnostic procedures and 2 to 50 for polypectomy. The
      severity sum score per 10,000 procedures was 26 for EGD, 67 for colonoscopy, and
      1185 for polypectomy. CONCLUSIONS: Outpatient endoscopy performed in practice
      settings by German gastroenterologists and internists is safe. The low
      complication rates may partly be explained by the high degree of experience
      resulting from the larger numbers of procedures performed relative to the numbers
      performed by gastroenterologists in hospitals and in other countries.

PMID- 11323589
TI  - Major hemorrhage from an unusual gastric tumor.

PMID- 11323590
TI  - Mirizzi's syndrome after cholecystectomy.

PMID- 11323591
TI  - Primary lymphoma of the major duodenal papilla.

PMID- 11323592
TI  - Endoscopic images of aortoesophageal fistula.

PMID- 11323593
TI  - Gastroduodenal intussusception.

PMID- 11323594
TI  - Direct percutaneous endoscopic jejunostomy with small bowel enteroscopy and
      fluoroscopy.
AB  - BACKGROUND: Approaches to the creation of a percutaneous jejunostomy (PEJ)
      include enteroscopy with jejunal transillumination, fluoroscopy with small bowel
      distension and tract dilation, and jejunal enteral tube placement through a
      percutaneous endoscopic gastrostomy. Although all have been successful, the
      combination of enteroscopy and fluoroscopy may improve visualization and the
      success of PEJ placement. This is a description of such a technique and its
      successful use in 7 patients. METHODS: The procedure was performed with the
      patient under conscious sedation in a manner similar to standard PEG placement.
      The proximal jejunum was visualized and a standard snare was passed though the
      enteroscope and was opened. A needle and guidewire were directed percutaneously
      though the snare by using fluoroscopic guidance. Under direct endoscopic
      visualization the snare was closed around the guidewire. A standard 20F push-type
      "gastrostomy" tube was passed over the guidewire and through the mouth and the
      dome seated in the jejunum. A bumper was passed externally over the tube and
      tightened at the skin. RESULTS: PEJ placement was successful in all 7 patients.
      The average length of the procedure was 40 minutes (range 22-64 minutes). There
      were no major complications. Mean follow-up was 124 days (range 28-308 days).
      Feeding tubes remained functional until removal (2), death (1), or surgical
      removal for an unrelated reason (1). Three tubes are still in use. CONCLUSIONS:
      Percutaneous endoscopic jejunostomy tube placement can be performed successfully
      with enteroscopy and fluoroscopy. This technique is safe and efficient and
      provides distal enteral nutritional support for patients in whom PEG cannot be
      used.

PMID- 11323595
TI  - Clinical application of a new colonoscope with variable insertion tube rigidity:
      a pilot study.
AB  - BACKGROUND: Colonic loop formation can prolong colonoscopy, increase patient
      discomfort, and preclude complete examination. A colonoscope with variable
      insertion tube rigidity may facilitate colonoscopy. Our aim was to determine
      whether the use of a colonoscope with variable insertion tube rigidity reduces
      insertion time and improves patient acceptance of colonoscopy. METHODS: Fifty
      patients were randomly assigned to undergo colonoscopy with a conventional
      colonoscope or a variable rigidity colonoscope (VRC). Patient acceptance, dosage
      of medication, use of abdominal pressure, and patient repositioning were
      assessed. Statistical analysis was performed by the 2-sample Wilcoxon rank sum
      test and an extension of Fisher exact test. RESULTS: The groups were comparable
      with respect to age, gender, and medications required during colonoscopy. The
      cecum was reached in all 25 patients who underwent colonoscopy with the VRC,
      including 1 patient in whom the cecum was not reached at a previous colonoscopy
      with a conventional instrument. In the conventional colonoscopy group, the cecum
      was not reached in 4 patients (2 poor preparation, 2 loop formation). There was
      no significant difference between the 2 groups with respect to insertion time. In
      the group that underwent colonoscopy with the variable rigidity instrument, less
      abdominal pressure was required (p = 0.05), and nursing assessment of patient
      discomfort was more favorable (p = 0.05). There were no complications and no
      significant differences in the intubation time to cecum or in repositioning,
      patient acceptance, or patient assessment of abdominal pain. CONCLUSION: The use
      of a variable rigidity colonoscope reduced the frequency of abdominal pressure
      but did not affect intubation time to cecum, repositioning, patient acceptance,
      or patient assessment of abdominal pain.

PMID- 11323596
TI  - Autofluorescence endoscopy: feasibility of detection of GI neoplasms unapparent
      to white light endoscopy with an evolving technology.
AB  - BACKGROUND: Case studies are presented of fluorescence endoscopy in the upper and
      lower GI tract to illustrate the ability to detect early-stage lesions that were
      not observable with white light endoscopy or those in which the assessment of the
      stage or extension of the lesion were equivocal. METHODS: A new fluorescence
      imaging system was used in which blue light excites the naturally-occurring
      fluorescence of tissues (autofluorescence). The system produces real-time, false
      color images that combine green and red fluorescence intensities. In general,
      abnormal lesions are seen to have an increase in the red-to-green fluorescence
      intensity compared with surrounding tissue. This system was evaluated in patients
      at 4 participating institutions, concurrently with standard white light
      endoscopy, with or without dye staining. RESULTS: Selected cases are presented in
      which fluorescence imaging identified specific lesions including focal high-grade
      dysplasia in Barrett's mucosa, signet ring carcinoma of the stomach, and flat
      adenoma in the colon. CONCLUSIONS: The capability of autofluorescence endoscopy
      to detect the presence and extent of occult malignant and premalignant GI lesions
      has been demonstrated. The future development and evaluation of this technology
      are discussed.

PMID- 11323597
TI  - Symptoms of hyperphosphatemia, hypocalcemia, and hypomagnesemia in an adolescent
      after the oral administration of sodium phosphate in preparation for a
      colonoscopy.

PMID- 11323598
TI  - Congo-red negative colonic amyloid with scalloping of the valvulae conniventes.

PMID- 11323599
TI  - Acute recurring pancreatitis: a manifestation of duodenal amyloid deposition.
      Case report and review.

PMID- 11323600
TI  - Ruptured aneurysm and gastric perforation associated with acute pancreatitis: a
      rare cause of hematemesis.

PMID- 11323601
TI  - Combined endoscopic variceal ligation and sclerotherapy for bleeding rectal
      varices associated with primary biliary cirrhosis: a case showing a long-lasting
      favorable response.

PMID- 11323603
TI  - Laparoscopic appearance of fasciola hepatica infection.

PMID- 11323602
TI  - Combined balloon-occluded embolization for treatment of concurrent duodenal,
      gastric, and esophageal varices: a case report.

PMID- 11323604
TI  - Hemoperitoneum after accidental dislodgement and subsequent replacement of PEG
      tube.

PMID- 11323605
TI  - Adult T-cell leukemia with an unusual esophageal lesion.

PMID- 11323606
TI  - Ectopic pancreas presenting as a submucosal gastric antral tumor that was cystic
      on EUS.

PMID- 11323607
TI  - Anisakiasis of the ileocecal valve.

PMID- 11323608
TI  - Endoscopic hemostasis for hemorrhage from gastric cancer complicated by double
      channel pylorus.

PMID- 11323609
TI  - Endoscopic drainage of malignant hilar obstruction: is one biliary stent enough
      or should we work to place two?

PMID- 11323610
TI  - A guideline for live endoscopy courses: an ASGE White Paper.

PMID- 11323611
TI  - Percutaneous transhepatic cholangioscopic examination: a necessity for the
      biliary endoscopist.

PMID- 11323612
TI  - Double injection technique to prevent complications of endoscopic tattooing.

PMID- 11323613
TI  - A wire-loop technique for removal of embedded biliary stents.

PMID- 11323615
TI  - Oral preparations for flexible sigmoidoscopy.

PMID- 11323617
TI  - Urea breath test for the diagnosis of Helicobacter pylori.

PMID- 11323619
TI  - The planning of clinical studies: statistical power, part I.

PMID- 11323621
TI  - Astronomy, goddesses and knowledge.

PMID- 11323620
TI  - Next steps against AIDS.

PMID- 11323622
TI  - Russia needs help to fend off potato famine, researchers warn.

PMID- 11323623
TI  - Smithsonian closure plan under fire.

PMID- 11323625
TI  - Reef gets off the starting blocks.

PMID- 11323624
TI  - Standards needed for foot-and-mouth tests.

PMID- 11323626
TI  - Japan speeds up mission to unravel genetic diseases.

PMID- 11323627
TI  - South Africa may keep door closed to generic AIDS drugs.

PMID- 11323628
TI  - US administration tries to repair green image.

PMID- 11323629
TI  - Tenure-track plan aims to end university inbreeding.

PMID- 11323630
TI  - Astronomers bargain for use of 'sacred' site.

PMID- 11323633
TI  - Cinderella goes to the ball.

PMID- 11323635
TI  - Precarious life in Spain.

PMID- 11323634
TI  - Even 'free access' is still beyond the means of most scholars in Africa.

PMID- 11323636
TI  - Let's reward innovative action against poverty.

PMID- 11323637
TI  - Entropy illustrates the flexibility of Chinese.

PMID- 11323639
TI  - Publishing on the semantic web.

PMID- 11323640
TI  - The self-archiving initiative.

PMID- 11323641
TI  - Setting logical priorities.

PMID- 11323647
TI  - Scientist's birthright.

PMID- 11323648
TI  - The genomic cosmos.

PMID- 11323649
TI  - Polio vaccines exonerated.

PMID- 11323651
TI  - Optics. Holograms of atoms.

PMID- 11323650
TI  - Palaeontology. Ruffling feathers.

PMID- 11323654
TI  - Earth science. Shaken, not stirred.

PMID- 11323653
TI  - Genome sequencing. A grin without a cat.

PMID- 11323655
TI  - Cancer. Improved mouse models.

PMID- 11323657
TI  - Polio vaccine samples not linked to AIDS.

PMID- 11323658
TI  - Vaccine safety. Analysis of oral polio vaccine CHAT stocks.

PMID- 11323659
TI  - Human immunodeficiency virus. Phylogeny and the origin of HIV-1.

PMID- 11323660
TI  - Chronobiology. Reversal of honeybee behavioural rhythms.

PMID- 11323661
TI  - Deep-mantle high-viscosity flow and thermochemical structure inferred from
      seismic and geodynamic data.
AB  - Surface geophysical data that are related to the process of thermal convection in
      the Earth's mantle provide constraints on the rheological properties and density
      structure of the mantle. We show that these convection-related data imply the
      existence of a region of very high effective viscosity near 2,000 km depth. This
      inference is obtained using a viscous-flow model based on recent high-resolution
      seismic models of three-dimensional structure in the mantle. The high-viscosity
      layer near 2,000 km depth results in a re-organization of flow from short to long
      horizontal length scales, which agrees with seismic tomographic observations of
      very long wavelength structures in the deep mantle. The high-viscosity region
      also strongly suppresses flow-induced deformation and convective mixing in the
      deep mantle. Here we predict compositional and thermal heterogeneity in this
      region, using viscous-flow calculations based on the new viscosity profile,
      together with independent mineral physics data. These maps are consistent with
      the anti-correlation of anomalies in seismic shear and bulk sound velocity in the
      deep mantle. The maps also show that mega-plumes in the lower mantle below the
      central Pacific and Africa are, despite the presence of compositional
      heterogeneity, buoyant and actively upwelling structures.

PMID- 11323662
TI  - Distinct roles of nerve and muscle in postsynaptic differentiation of the
      neuromuscular synapse.
AB  - The development of chemical synapses is regulated by interactions between pre-
      and postsynaptic cells. At the vertebrate skeletal neuromuscular junction, the
      organization of an acetylcholine receptor (AChR)-rich postsynaptic apparatus has
      been well studied. Much evidence suggests that the nerve-derived protein agrin
      activates muscle-specific kinase (MuSK) to cluster AChRs through the synapse
      specific cytoplasmic protein rapsyn. But how postsynaptic differentiation is
      initiated, or why most synapses are restricted to an 'end-plate band' in the
      middle of the muscle remains unknown. Here we have used genetic methods to
      address these issues. We report that the initial steps in postsynaptic
      differentiation and formation of an end-plate band require MuSK and rapsyn, but
      are not dependent on agrin or the presence of motor axons. In contrast, the
      subsequent stages of synaptic growth and maintenance require nerve-derived agrin,
      and a second nerve-derived signal that disperses ectopic postsynaptic apparatus.

PMID- 11323663
TI  - A phenomenological description of space-time noise in quantum gravity.
AB  - Space-time 'foam' is a geometric picture of the smallest size scales in the
      Universe, which is characterized mainly by the presence of quantum uncertainties
      in the measurement of distances. All quantum-gravity theories should predict some
      kind of foam, but the description of the properties of this foam varies according
      to the theory, thereby providing a possible means of distinguishing between such
      theories. I previously showed that foam-induced distance fluctuations would
      introduce a new source of noise to the measurements of gravity-wave
      interferometers, but the theories are insufficiently developed to permit detailed
      predictions that would be of use to experimentalists. Here I propose a
      phenomenological approach that directly describes space-time foam, and which
      leads naturally to a picture of distance fluctuations that is independent of the
      details of the interferometer. The only unknown in the model is the length scale
      that sets the overall magnitude of the effect, but recent data already rule out
      the possibility that this length scale could be identified with the 'string
      length' (10-34 m < Ls < 10-33 m). Length scales even smaller than the 'Planck
      length' (LP approximately 10-35 m) will soon be probed experimentally.

PMID- 11323664
TI  - Entanglement purification for quantum communication.
AB  - The distribution of entangled states between distant locations will be essential
      for the future large-scale realization of quantum communication schemes such as
      quantum cryptography and quantum teleportation. Because of unavoidable noise in
      the quantum communication channel, the entanglement between two particles is more
      and more degraded the further they propagate. Entanglement purification is thus
      essential to distil highly entangled states from less entangled ones. Existing
      general purification protocols are based on the quantum controlled-NOT (CNOT) or
      similar quantum logic operations, which are very difficult to implement
      experimentally. Present realizations of CNOT gates are much too imperfect to be
      useful for long-distance quantum communication. Here we present a scheme for the
      entanglement purification of general mixed entangled states, which achieves 50
      per cent of the success probability of schemes based on the CNOT operation, but
      requires only simple linear optical elements. Because the perfection of such
      elements is very high, the local operations necessary for purification can be
      performed with the required precision. Our procedure is within the reach of
      current technology, and should significantly simplify the implementation of long
      distance quantum communication.

PMID- 11323665
TI  - Mobile silver ions and glass formation in solid electrolytes.
AB  - Solid electrolytes are a class of materials in which the cationic or anionic
      constituents are not confined to specific lattice sites, but are essentially free
      to move throughout the structure. The solid electrolytes AgI and Ag2Se (refs 1,
      2, 3, 4, 5, 6, 7) are of interest for their use as additives in network glasses,
      such as chalcogenides and oxides, because the resulting composite glasses can
      show high electrical conductivities with potential applications for batteries,
      sensors and displays. Here we show that these composite glasses can exhibit two
      distinct types of molecular structures-an intrinsic phase-separation that results
      in a bimodal distribution of glass transition temperatures, and a microscopically
      homogeneous network displaying a single glass transition temperature. For the
      first case, the two transition temperatures correspond to the solid-electrolyte
      glass phase and the main glass phase (the 'base glass'), enabling us to show that
      the glass transition temperatures for the AgI and Ag2Se phases are respectively
      75 and 230 degrees C. Furthermore, we show that the magnitude of the bimodal
      glass transition temperatures can be quantitatively understood in terms of
      network connectivity, provided that the Ag+ cations undergo fast-ion motion in
      the glasses. These results allow us to unambiguously distinguish base glasses in
      which these additives are homogeneously alloyed from those in which an intrinsic
      phase separation occurs, and to provide clues to understanding ion-transport
      behaviour in these superionic conductors.

PMID- 11323666
TI  - Absence of deep-water formation in the Labrador Sea during the last interglacial
      period.
AB  - The two main constituent water masses of the deep North Atlantic Ocean-North
      Atlantic Deep Water at the bottom and Labrador Sea Water at an intermediate level
      are currently formed in the Nordic seas and the Labrador Sea, respectively. The
      rate of formation of these two water masses tightly governs the strength of the
      global ocean circulation and the associated heat transport across the North
      Atlantic Ocean. Numerical simulations have suggested a possible shut-down of
      Labrador Sea Water formation as a consequence of global warming. Here we use
      micropalaeontological data and stable isotope measurements in both planktonic and
      benthic foraminifera from deep Labrador Sea cores to investigate the density
      structure of the water column during the last interglacial period, which was
      thought to be about 2 degrees C warmer than present. Our results indicate that
      today's stratification between Labrador Sea Water and North Atlantic Deep Water
      never developed during the last interglacial period. Instead, a buoyant surface
      layer was present above a single water mass originating from the Nordic seas.
      Thus the present situation, with an active site of intermediate-water formation
      in the Labrador Sea, which settled some 7,000 years ago, has no analogue
      throughout the last climate cycle.

PMID- 11323667
TI  - Evidence from the Pacific troposphere for large global sources of oxygenated
      organic compounds.
AB  - The presence of oxygenated organic compounds in the troposphere strongly
      influences key atmospheric processes. Such oxygenated species are, for example,
      carriers of reactive nitrogen and are easily photolysed, producing free radicals
      and so influence the oxidizing capacity and the ozone-forming potential of the
      atmosphere-and may also contribute significantly to the organic component of
      aerosols. But knowledge of the distribution and sources of oxygenated organic
      compounds, especially in the Southern Hemisphere, is limited. Here we
      characterize the tropospheric composition of oxygenated organic species, using
      data from a recent airborne survey conducted over the tropical Pacific Ocean (30
      degrees N to 30 degrees S). Measurements of a dozen oxygenated chemicals
      (carbonyls, alcohols, organic nitrates, organic pernitrates and peroxides), along
      with several C2-C8 hydrocarbons, reveal that abundances of oxygenated species are
      extremely high, and collectively, oxygenated species are nearly five times more
      abundant than non-methane hydrocarbons in the Southern Hemisphere. Current
      atmospheric models are unable to correctly simulate these findings, suggesting
      that large, diffuse, and hitherto-unknown sources of oxygenated organic compounds
      must therefore exist. Although the origin of these sources is still unclear, we
      suggest that oxygenated species could be formed via the oxidation of hydrocarbons
      in the atmosphere, the photochemical degradation of organic matter in the oceans,
      and direct emissions from terrestrial vegetation.

PMID- 11323668
TI  - Hemispherical variations in seismic velocity at the top of the Earth's inner
      core.
AB  - Knowledge of the seismic velocity structure at the top of the Earth's inner core
      is important for deciphering the physical processes responsible for inner-core
      growth. Previous global seismic studies have focused on structures found 100 km
      or deeper within the inner core, with results for the uppermost 100 km available
      for only isolated regions. Here we present constraints on seismic velocity
      variations just beneath the inner-core boundary, determined from the difference
      in travel time between waves reflected at the inner-core boundary and those
      transmitted through the inner core. We found that these travel-time residuals
      observed on both global seismograph stations and several regional seismic
      networks-are systematically larger, by about 0.8 s, for waves that sample the
      'eastern hemisphere' of the inner core (40 degrees E to 180 degrees E) compared
      to those that sample the 'western hemisphere' (180 degrees W to 40 degrees E).
      These residuals show no correlation with the angle at which the waves traverse
      the inner core; this indicates that seismic anisotropy is not strong in this
      region and that the isotropic seismic velocity of the eastern hemisphere is about
      0.8% higher than that of the western hemisphere.

PMID- 11323669
TI  - The distribution of integumentary structures in a feathered dinosaur.
AB  - Non-avian theropod dinosaurs with preserved integumentary coverings are becoming
      more common; but apart from the multiple specimens of Caudipteryx, which have
      true feathers, animals that are reasonably complete and entirely articulated that
      show these structures in relation to the body have not been reported. Here we
      report on an enigmatic small theropod dinosaur that is covered with filamentous
      feather-like structures over its entire body.

PMID- 11323670
TI  - Genetic evidence for Near-Eastern origins of European cattle.
AB  - The limited ranges of the wild progenitors of many of the primary European
      domestic species point to their origins further east in Anatolia or the fertile
      crescent. The wild ox (Bos primigenius), however, ranged widely and it is unknown
      whether it was domesticated within Europe as one feature of a local contribution
      to the farming economy. Here we examine mitochondrial DNA control-region sequence
      variation from 392 extant animals sampled from Europe, Africa and the Near East,
      and compare this with data from four extinct British wild oxen. The ancient
      sequences cluster tightly in a phylogenetic analysis and are clearly distinct
      from modern cattle. Network analysis of modern Bos taurus identifies four star
      like clusters of haplotypes, with intra-cluster diversities that approximate to
      that expected from the time depth of domestic history. Notably, one of these
      clusters predominates in Europe and is one of three encountered at substantial
      frequency in the Near East. In contrast, African diversity is almost exclusively
      composed of a separate haplogroup, which is encountered only rarely elsewhere.
      These data provide strong support for a derived Near-Eastern origin for European
      cattle.

PMID- 11323671
TI  - The highly reduced genome of an enslaved algal nucleus.
AB  - Chromophyte algae differ fundamentally from plants in possessing chloroplasts
      that contain chlorophyll c and that have a more complex bounding-membrane
      topology. Although chromophytes are known to be evolutionary chimaeras of a red
      alga and a non-photosynthetic host, which gave rise to their exceptional membrane
      complexity, their cell biology is poorly understood. Cryptomonads are the only
      chromophytes that still retain the enslaved red algal nucleus as a minute
      nucleomorph. Here we report complete sequences for all three nucleomorph
      chromosomes from the cryptomonad Guillardia theta. This tiny 551-kilobase
      eukaryotic genome is the most gene-dense known, with only 17 diminutive
      spliceosomal introns and 44 overlapping genes. Marked evolutionary compaction
      hundreds of millions of years ago eliminated nearly all the nucleomorph genes for
      metabolic functions, but left 30 for chloroplast-located proteins. To allow
      expression of these proteins, nucleomorphs retain hundreds of genetic
      housekeeping genes. Nucleomorph DNA replication and periplastid protein synthesis
      require the import of many nuclear gene products across endoplasmic reticulum and
      periplastid membranes. The chromosomes have centromeres, but possibly only one
      loop domain, offering a means for studying eukaryotic chromosome replication,
      segregation and evolution.

PMID- 11323672
TI  - Nonlinear effects of large-scale climatic variability on wild and domestic
      herbivores.
AB  - Large-scale climatic fluctuations, such as the North Atlantic Oscillation (NAO),
      have been shown to affect many ecological processes. Such effects have been
      typically assumed to be linear. Only one study has reported a nonlinear relation;
      however, that nonlinear relation was monotonic (that is, no reversal). Here we
      show that there is a strong nonlinear and non-monotonic (that is, reversed)
      effect of the NAO on body weight during the subsequent autumn for 23,838
      individual wild red deer (Cervus elaphus) and 139,485 individual domestic sheep
      (Ovis aries) sampled over several decades on the west coast of Norway. These
      relationships are, at least in part, explained by comparable nonlinear and non
      monotonic relations between the NAO and local climatic variables (temperature,
      precipitation and snow depth). The similar patterns observed for red deer and
      sheep, the latter of which live indoors during winter and so experience a stable
      energy supply in winter, suggest that the (winter) climatic variability (for
      which the index is a proxy) must influence the summer foraging conditions
      directly or indirectly.

PMID- 11323673
TI  - The innate immune response to bacterial flagellin is mediated by Toll-like
      receptor 5.
AB  - The innate immune system recognizes pathogen-associated molecular patterns
      (PAMPs) that are expressed on infectious agents, but not on the host. Toll-like
      receptors (TLRs) recognize PAMPs and mediate the production of cytokines
      necessary for the development of effective immunity. Flagellin, a principal
      component of bacterial flagella, is a virulence factor that is recognized by the
      innate immune system in organisms as diverse as flies, plants and mammals. Here
      we report that mammalian TLR5 recognizes bacterial flagellin from both Gram
      positive and Gram-negative bacteria, and that activation of the receptor
      mobilizes the nuclear factor NF-kappaB and stimulates tumour necrosis factor
      alpha production. TLR5-stimulating activity was purified from Listeria
      monocytogenes culture supernatants and identified as flagellin by tandem mass
      spectrometry. Expression of L. monocytogenes flagellin in non-flagellated
      Escherichia coli conferred on the bacterium the ability to activate TLR5, whereas
      deletion of the flagellin genes from Salmonella typhimurium abrogated TLR5
      stimulating activity. All known TLRs signal through the adaptor protein MyD88.
      Mice challenged with bacterial flagellin rapidly produced systemic interleukin-6,
      whereas MyD88-null mice did not respond to flagellin. Our data suggest that TLR5,
      a member of the evolutionarily conserved Toll-like receptor family, has evolved
      to permit mammals specifically to detect flagellated bacterial pathogens.

PMID- 11323674
TI  - TREM-1 amplifies inflammation and is a crucial mediator of septic shock.
AB  - Host innate responses to bacterial infections are primarily mediated by
      neutrophils and monocytes/macrophages. These cells express pattern recognition
      receptors (PRRs) that bind conserved molecular structures shared by groups of
      microorganisms. Stimulation of PRR signalling pathways initiates secretion of
      proinflammatory mediators, which promote the elimination of infectious agents and
      the induction of tissue repair. Excessive inflammation owing to bacterial
      infections can lead to tissue damage and septic shock. Here we show that
      inflammatory responses to microbial products are amplified by a pathway mediated
      by triggering receptor expressed on myeloid cells (TREM)-1. TREM-1 is an
      activating receptor expressed at high levels on neutrophils and monocytes that
      infiltrate human tissues infected with bacteria. Furthermore, it is upregulated
      on peritoneal neutrophils of patients with microbial sepsis and mice with
      experimental lipopolysaccaride (LPS)-induced shock. Notably, blockade of TREM-1
      protects mice against LPS-induced shock, as well as microbial sepsis caused by
      live Escherichia coli or caecal ligation and puncture. These results demonstrate
      a critical function of TREM-1 in acute inflammatory responses to bacteria and
      implicate TREM-1 as a potential therapeutic target for septic shock.

PMID- 11323675
TI  - IFNgamma and lymphocytes prevent primary tumour development and shape tumour
      immunogenicity.
AB  - Lymphocytes were originally thought to form the basis of a 'cancer
      immunosurveillance' process that protects immunocompetent hosts against primary
      tumour development, but this idea was largely abandoned when no differences in
      primary tumour development were found between athymic nude mice and syngeneic
      wild-type mice. However, subsequent observations that nude mice do not completely
      lack functional T cells and that two components of the immune system-IFNgamma and
      perforin-help to prevent tumour formation in mice have led to renewed interest in
      a tumour-suppressor role for the immune response. Here we show that lymphocytes
      and IFNgamma collaborate to protect against development of carcinogen-induced
      sarcomas and spontaneous epithelial carcinomas and also to select for tumour
      cells with reduced immunogenicity. The immune response thus functions as an
      effective extrinsic tumour-suppressor system. However, this process also leads to
      the immunoselection of tumour cells that are more capable of surviving in an
      immunocompetent host, which explains the apparent paradox of tumour formation in
      immunologically intact individuals.

PMID- 11323676
TI  - Somatic activation of the K-ras oncogene causes early onset lung cancer in mice.
AB  - About 30% of human tumours carry ras gene mutations. Of the three genes in this
      family (composed of K-ras, N-ras and H-ras), K-ras is the most frequently mutated
      member in human tumours, including adenocarcinomas of the pancreas (
      approximately 70-90% incidence), colon ( approximately 50%) and lung (
      approximately 25-50%). To construct mouse tumour models involving K-ras, we used
      a new gene targeting procedure to create mouse strains carrying oncogenic alleles
      of K-ras that can be activated only on a spontaneous recombination event in the
      whole animal. Here we show that mice carrying these mutations were highly
      predisposed to a range of tumour types, predominantly early onset lung cancer.
      This model was further characterized by examining the effects of germline
      mutations in the tumour suppressor gene p53, which is known to be mutated along
      with K-ras in human tumours. This approach has several advantages over
      traditional transgenic strategies, including that it more closely recapitulates
      spontaneous oncogene activation as seen in human cancers.

PMID- 11323677
TI  - CONSTANS mediates between the circadian clock and the control of flowering in
      Arabidopsis.
AB  - Flowering is often triggered by exposing plants to appropriate day lengths. This
      response requires an endogenous timer called the circadian clock to measure the
      duration of the day or night. This timer also controls daily rhythms in gene
      expression and behavioural patterns such as leaf movements. Several Arabidopsis
      mutations affect both circadian processes and flowering time; but how the effect
      of these mutations on the circadian clock is related to their influence on
      flowering remains unknown. Here we show that expression of CONSTANS (CO), a gene
      that accelerates flowering in response to long days, is modulated by the
      circadian clock and day length. Expression of a CO target gene, called FLOWERING
      LOCUS T (FT), is restricted to a similar time of day as expression of CO. Three
      mutations that affect circadian rhythms and flowering time alter CO and FT
      expression in ways that are consistent with their effects on flowering. In
      addition, the late flowering phenotype of such mutants is corrected by
      overexpressing CO. Thus, CO acts between the circadian clock and the control of
      flowering, suggesting mechanisms by which day length regulates flowering time.

PMID- 11323678
TI  - Structure of the gating domain of a Ca2+-activated K+ channel complexed with
      Ca2+/calmodulin.
AB  - Small-conductance Ca2+-activated K+ channels (SK channels) are independent of
      voltage and gated solely by intracellular Ca2+. These membrane channels are
      heteromeric complexes that comprise pore-forming alpha-subunits and the Ca2+
      binding protein calmodulin (CaM). CaM binds to the SK channel through the CaM
      binding domain (CaMBD), which is located in an intracellular region of the alpha
      subunit immediately carboxy-terminal to the pore. Channel opening is triggered
      when Ca2+ binds the EF hands in the N-lobe of CaM. Here we report the 1.60 A
      crystal structure of the SK channel CaMBD/Ca2+/CaM complex. The CaMBD forms an
      elongated dimer with a CaM molecule bound at each end; each CaM wraps around
      three alpha-helices, two from one CaMBD subunit and one from the other. As only
      the CaM N-lobe has bound Ca2+, the structure provides a view of both calcium
      dependent and -independent CaM/protein interactions. Together with biochemical
      data, the structure suggests a possible gating mechanism for the SK channel.

PMID- 11323681
TI  - Creating the thirst.

PMID- 11323682
TI  - TH1 and TH2 cytokine control of thyrocyte survival in thyroid autoimmunity.

PMID- 11323684
TI  - Immunology in the post-genomic era.

PMID- 11323685
TI  - To live and let die.

PMID- 11323686
TI  - Blueprints for life or death.

PMID- 11323687
TI  - The CD8 response on autopilot.

PMID- 11323688
TI  - Helper T cell differentiation: a role for SAP?

PMID- 11323689
TI  - HIV-1 Nef: negative effector of Fas?

PMID- 11323691
TI  - CD45: new jobs for an old acquaintance.
AB  - Identified as the first and prototypic transmembrane protein tyrosine phosphatase
      (PTPase), CD45 has been extensively studied for over two decades and is thought
      to be important for positively regulating antigen-receptor signaling via the
      dephosphorylation of Src kinases. However, new evidence indicates that CD45 can
      function as a Janus kinase PTPase that negatively controls cytokine-receptor
      signaling. A point mutation in CD45, which appears to affect CD45 dimerization,
      and a genetic polymorphism that affects alternative CD45 splicing are implicated
      in autoimmunity in mice and multiple sclerosis in humans. CD45 is expressed in
      multiple isoforms and the modulation of specific CD45 splice variants with
      antibodies can prevent transplant rejections. In addition, loss of CD45 can
      affect microglia activation in a mouse model for Alzheimer's disease. Thus, CD45
      is moving rapidly back into the spotlight as a drug target and central regulator
      involved in differentiation of multiple hematopoietic cell lineages, autoimmunity
      and antiviral immunity.

PMID- 11323692
TI  - Immunological adjuvants promote activated T cell survival via induction of Bcl-3.
AB  - Injection of soluble protein antigen into animals causes abortive proliferation
      of the responding T cells. Immunological adjuvants boost T cell responses at
      least in part by increasing the survival of activated T cells during and after
      the initial proliferative phase of their clonal expansion. To understand how
      adjuvants promote T cell survival, we used gene microarrays to analyze gene
      expression in T cells activated either with antigen alone or in the presence of
      two different adjuvants. Among the genes whose expression was increased by both
      adjuvants was the IkappaB family member Bcl-3. Retroviral infection experiments
      showed that expression of Bcl-3 increased survival of activated T cells in vitro
      and in vivo. Adjuvants may therefore improve survival of activated T cells via
      induction of Bcl-3.

PMID- 11323693
TI  - Constitutive pre-TCR signaling promotes differentiation through Ca2+ mobilization
      and activation of NF-kappaB and NFAT.
AB  - Pre-T cell antigen receptor (pre-TCR) signaling plays a crucial role in the
      development of immature T cells. Although certain aspects of proximal pre-TCR
      signaling have been studied, the intermediate signal transducers and the distal
      transcription modulators have been poorly characterized. We report here a
      correlation between pre-TCR signaling and a biphasic rise in the cytosolic Ca2+
      concentration. In addition, we show that constitutive pre-TCR signaling is
      associated with an increased rate of Ca2+ influx through store-operated plasma
      membrane Ca2+ channels. We show also that the biphasic nature of the observed pre
      TCR-induced rise in cytosolic Ca2+ differentially modulates the activities of the
      transcription factors NF-kappaB and NFAT in developing T cells.

PMID- 11323694
TI  - SAP controls T cell responses to virus and terminal differentiation of TH2 cells.
AB  - SH2D1A, which encodes signaling lymphocyte activation molecule (SLAM)-associated
      protein (SAP), is altered in patients with X-linked lymphoproliferative disease
      (XLP), a primary immunodeficiency. SAP-deficient mice infected with lymphocytic
      choriomeningitis virus had greatly increased numbers of CD8+ and CD4+ interferon
      gamma-producing spleen and liver cells compared to wild-type mice. The immune
      responses of SAP-deficient mice to infection with Leishmania major together with
      in vitro studies showed that activated SAP-deficient T cells had an impaired
      ability to differentiate into T helper 2 cells. The aberrant immune responses in
      SAP-deficient mice show that SAP controls several distinct key T cell signal
      transduction pathways, which explains in part the complexity of the XLP
      phenotypes.

PMID- 11323695
TI  - Memory CD8+ T cell differentiation: initial antigen encounter triggers a
      developmental program in naive cells.
AB  - The rules that govern memory T cell differentiation are not well understood. This
      study shows that after antigenic stimulation naive CD8+ T cells become committed
      to dividing at least seven times and differentiating into effector and memory
      cells. Once the parental naive CD8+ T cell had been activated, this developmental
      process could not be interrupted and the daughter cells continued to divide and
      differentiate in the absence of further antigenic stimulation. These data
      indicate that initial antigen encounter triggers an instructive developmental
      program that does not require further antigenic stimulation and does not cease
      until memory CD8+ T cell formation.

PMID- 11323696
TI  - Naive CTLs require a single brief period of antigenic stimulation for clonal
      expansion and differentiation.
AB  - In defense of the host, the immune system must often raise an effective cytotoxic
      T lymphocyte (CTL) response from a small number of clonal precursors. The degree
      to which activation stimuli regulate the expansion and differentiation of naive
      CTLs, however, remains unknown. Using an engineered antigen-presenting cell (APC)
      system that allows control over antigenic stimulation, we studied the signaling
      duration requirements for priming and clonal expansion of naive CTLs. We found
      that naive CTLs become committed after as little as 2 h of exposure to APCs and
      that their subsequent division and differentiation can occur without the need for
      further antigenic stimulation of the daughter cells, whether priming is in vitro
      or in vivo. These data show that after a brief interaction with stimulatory APCs,
      naive CTLs initiate a program for their autonomous clonal expansion and
      development into functional effectors.

PMID- 11323697
TI  - Involvement of inhibitory NKRs in the survival of a subset of memory-phenotype
      CD8+ T cells.
AB  - Inhibitory natural killer receptors (NKRs) such as killer cell immunoglobulin
      like receptors (KIRs) in humans and Ly49 molecules in mice are expressed on NK
      cells and recognize multiple major histocompatibility (MHC) class I proteins. In
      humans and mice, a subset of CD8+ T cells also expresses NKRs and harbors a
      memory phenotype. Using mice that are transgenic for KIR2DL3 and its cognate HLA
      Cw3 ligand, we show that engagement of inhibitory NKRs selectively drives the in
      vivo accumulation of a subset of memory-phenotype CD8+ T cells that express the
      beta chain of the interleukin 2 receptor. In vitro, recognition of MHC class I
      molecules by inhibitory NKRs on T cells down-regulated activation-induced cell
      death. These results unveil an MHC class I-dependent pathway that promotes the
      survival of a subset of memory-phenotype CD8+ T cells and also reveal an
      unexpected biological function for inhibitory NKRs on T cells.

PMID- 11323698
TI  - gp49B1-alpha(v)beta3 interaction inhibits antigen-induced mast cell activation.
AB  - We have identified the integrin alpha(v)beta3 as a ligand for mouse gp49B1, thus
      identifying a new class of ligand for a member of the family of inhibitory
      immunoreceptors that bear C2-type immunoglobulin-like domains. The specific
      interaction was shown by both cell-protein and cell-cell binding assays. In
      addition, we found that the interaction of alpha(v)beta3 with gp49B1 on bone
      marrow-derived mouse mast cells inhibited antigen-induced immunoglobulin E
      mediated cell activation. Because neither gp49B1 nor alpha(v)beta3 exhibit
      substantive allelic variation, their newly appreciated interaction may reflect an
      innate pathway for down-regulating the activity of mast cells.

PMID- 11323699
TI  - Complex structure of the activating immunoreceptor NKG2D and its MHC class I-like
      ligand MICA.
AB  - The major histocompatibility complex (MHC) class I homolog, MICA, is a stress
      inducible ligand for NKG2D, a C-type lectin-like activating immunoreceptor. The
      crystal structure of this ligand-receptor complex that we report here reveals an
      NKG2D homodimer bound to a MICA monomer in an interaction that is analogous to
      that seen in T cell receptor-MHC class I protein complexes. Similar surfaces on
      each NKG2D monomer interact with different surfaces on either the alpha1 or
      alpha2 domains of MICA. The binding interactions are large in area and highly
      complementary. The central section of the alpha2-domain helix, disordered in the
      structure of MICA alone, is ordered in the complex and forms part of the NKG2D
      interface. The extensive flexibility of the interdomain linker of MICA is shown
      by its altered conformation when crystallized alone or in complex with NKG2D.

PMID- 11323700
TI  - Crystal structure of the human natural killer cell inhibitory receptor KIR2DL1
      HLA-Cw4 complex.
AB  - Inhibitory natural killer (NK) cell receptors down-regulate the cytotoxicity of
      NK cells upon recognition of specific class I major histocompatibility complex
      (MHC) molecules on target cells. We report here the crystal structure of the
      inhibitory human killer cell immunoglobulin-like receptor 2DL1 (KIR2DL1) bound to
      its class I MHC ligand, HLA-Cw4. The KIR2DL1-HLA-Cw4 interface exhibits charge
      and shape complementarity. Specificity is mediated by a pocket in KIR2DL1 that
      hosts the Lys80 residue of HLA-Cw4. Many residues conserved in HLA-C and in
      KIR2DL receptors make different interactions in KIR2DL1-HLA-Cw4 and in a
      previously reported KIR2DL2-HLA-Cw3 complex. A dimeric aggregate of KIR-HLA-C
      complexes was observed in one KIR2DL1-HLA-Cw4 crystal. Most of the amino acids
      that differ between human and chimpanzee KIRs with HLA-C specificities form
      solvent-accessible clusters outside the KIR-HLA interface, which suggests
      undiscovered interactions by KIRs.

PMID- 11323705
TI  - Proline not the only culprit?

PMID- 11323701
TI  - Disrupting Il13 impairs production of IL-4 specified by the linked allele.
AB  - Interleukin 13-deficient (IL-13-/-) mice express a defect in priming for IL-4
      production that is not corrected by adding IL-13 to the priming culture. This is
      partly accounted for by the consumption of IL-4 without endogenous replacement
      during culture of IL-13-/- CD4+ T cells. We examined cells from mice in which
      disrupted Il13 was linked to wild-type Il4 on one chromosome and wild-type Il13
      was linked to a "knocked-in" green fluorescent protein (Gfp) gene in the Il4
      locus. Our results show that the deficit in IL-4 production was due, at least in
      part, to a cis effect, in which disrupted Il13 diminished IL-4 production from
      the linked Il4 gene.

PMID- 11323706
TI  - RNA is all you need.

PMID- 11323707
TI  - DNA-binding by Ig-fold proteins.

PMID- 11323708
TI  - Over the rainbow to translational control.

PMID- 11323709
TI  - Proteins that bind RNA and the labs who love them.
AB  - RNA-protein interactions were the subject of a recent meeting in Austin, Texas.
      The program provided a current snapshot of the state of our understanding of how
      proteins help mediate the many functions of RNA.

PMID- 11323710
TI  - Picture story. Reining in CDK.

PMID- 11323711
TI  - The birth of computational structural biology.

PMID- 11323712
TI  - A structural view of mitochondria-mediated apoptosis.
AB  - Mitochondria-mediated apoptosis plays a central role in animal development and
      tissue homeostasis, and its alteration results in a range of malignant disorders
      including cancer. Upon apoptotic stimuli, the mitochondrial proteins cytochrome c
      and Smac/DIABLO are released into the cytosol, where they synergistically
      activate caspases by activating Apaf-1 and relieving the apoptotic inhibition by
      IAPs. Recent biochemical and structural studies reveal a molecular basis for
      these important events and identify an evolutionarily conserved mechanism of
      apoptosis from fruit flies to mammals.

PMID- 11323713
TI  - Crystal structure of a bifunctional transformylase and cyclohydrolase enzyme in
      purine biosynthesis.
AB  - ATIC, the product of the purH gene, is a 64 kDa bifunctional enzyme that
      possesses the final two activities in de novo purine biosynthesis, AICAR
      transformylase and IMP cyclohydrolase. The crystal structure of avian ATIC has
      been determined to 1.75 A resolution by the MAD method using a Se-methionine
      modified enzyme. ATIC forms an intertwined dimer with an extensive interface of
      approximately 5,000 A(2) per monomer. Each monomer is composed of two novel,
      separate functional domains. The N-terminal domain (up to residue 199) is
      responsible for the IMPCH activity, whereas the AICAR Tfase activity resides in
      the C-terminal domain (200-593). The active sites of the IMPCH and AICAR Tfase
      domains are approximately 50 A apart, with no structural evidence of a tunnel
      connecting the two active sites. The crystal structure of ATIC provides a
      framework to probe both catalytic mechanisms and to design specific inhibitors
      for use in cancer chemotherapy and inflammation.

PMID- 11323714
TI  - Solution structure of a Nedd4 WW domain-ENaC peptide complex.
AB  - Nedd4 is a ubiquitin protein ligase composed of a C2 domain, three (or four) WW
      domains and a ubiquitin ligase Hect domain. Nedd4 was demonstrated to bind the
      epithelial sodium channel (alphabetagammaENaC), by association of its WW domains
      with PY motifs (XPPXY) present in each ENaC subunit, and to regulate the cell
      surface stability of the channel. The PY motif of betaENaC is deleted or mutated
      in Liddle syndrome, a hereditary form of hypertension caused by elevated ENaC
      activity. Here we report the solution structure of the third WW domain of Nedd4
      complexed to the PY motif-containing region of betaENaC (TLPIPGTPPPNYDSL,
      referred to as betaP2). A polyproline type II helical conformation is adopted by
      the PPPN sequence. Unexpectedly, the C-terminal sequence YDSL forms a helical
      turn and both the tyrosine and the C-terminal leucine contact the WW domain. This
      is unlike other proline-rich peptides complexed to WW domains, which bind in an
      extended conformation and lack molecular interactions with residues C-terminal to
      the tyrosine or the structurally equivalent residue in non-PY motif WW domain
      targets. The Nedd4 WW domain-ENaC betaP2 peptide structure expands our
      understanding of the mechanisms involved in WW domain-ligand recognition and the
      molecular basis of Liddle syndrome.

PMID- 11323715
TI  - C-terminal opening mimics 'inside-out' activation of integrin alpha5beta1.
AB  - Integrins are adhesion molecules that convey signals both to and from the
      cytoplasm across the plasma membrane. In resting cells, integrins in a low
      affinity state can be activated by 'inside-out signaling', in which signals
      affecting integrin heterodimer cytoplasmic domains cause a conformational change
      in the integrin ligand-binding headpiece connected to the membrane by two long,
      approximately 16 nm stalks. Here we demonstrate a mechanism for conveying a
      conformational change over the long distance from the plasma membrane to the
      headpiece. We prepared soluble, alpha5beta1 integrin heterodimer extracellular
      fragments in which interactions between alpha- and beta-subunit cytoplasmic
      domains were replaced with an artificial clasp. Release of this C-terminal clasp
      by specific protease cleavage resulted in an approximately 14 nm separation of
      the stalks coupled to increased binding to fibronectin. This activation did not
      require any associated molecules or clustering and was observed with
      physiological concentrations of divalent cations. These findings suggest that the
      overall mechanism for integrin inside-out activation involves the spatial
      separation of the cytoplasmic and/or transmembrane domains.

PMID- 11323716
TI  - UBA domains of DNA damage-inducible proteins interact with ubiquitin.
AB  - Rad23 is a highly conserved protein involved in nucleotide excision repair (NER)
      that associates with the proteasome via its N-terminus. Its C-terminal ubiquitin
      associated (UBA) domain is evolutionarily conserved from yeast to humans.
      However, the cellular function of UBA domains is not completely understood.
      Recently, RAD23 and DDI1, both DNA damage-inducible genes encoding proteins with
      UBA domains, were implicated genetically in Pds1-dependent mitotic control in
      yeast. The UBA domains of RAD23 and DDI1 are required for these interactions.
      Timely degradation of Pds1 via the ubiquitin/proteasome pathway allows anaphase
      onset and is crucial for chromosome maintenance. Here, we show that Rad23 and
      Ddi1 interact directly with ubiquitin and that this interaction is dependent on
      their UBA domains, providing a possible mechanism for UBA-dependent cell cycle
      control. Moreover, we show that a hydrophobic surface on the UBA domain, which
      from structural work had been predicted to be a protein-protein interaction
      interface, is indeed required for ubiquitin binding. By demonstrating that UBA
      domains interact with ubiquitin, we have provided the first indication of a
      cellular function for the UBA domain.

PMID- 11323717
TI  - Direct structural evidence for a concerted allosteric transition in Escherichia
      coli aspartate transcarbamoylase.
AB  - Regulation of protein function, often achieved by allosteric mechanisms, is
      central to normal physiology and cellular processes. Although numerous models
      have been proposed to account for the cooperative binding of ligands to
      allosteric proteins and enzymes, direct structural support has been lacking.
      Here, we used a combination of X-ray crystallography and small angle X-ray
      scattering in solution to provide direct structural evidence that the binding of
      ligand to just one of the six active sites of Escherichia coli aspartate
      transcarbamoylase induces a concerted structural transition from the T to the R
      state.

PMID- 11323718
TI  - Tuning of chaperone activity of Hsp70 proteins by modulation of nucleotide
      exchange.
AB  - The Hsp70 chaperone activity in protein folding is regulated by ATP-controlled
      cycles of substrate binding and release. Nucleotide exchange plays a key role in
      these cycles by triggering substrate release. Structural searches of Hsp70
      homologs revealed three structural elements within the ATPase domain: two salt
      bridges and an exposed loop. Mutational analysis showed that these elements
      control the dissociation of nucleotides, the interaction with exchange factors
      and chaperone activity. Sequence variations in the three elements classify the
      Hsp70 family members into three subfamilies, DnaK proteins, HscA proteins and
      Hsc70 proteins. These subfamilies show strong differences in nucleotide
      dissociation and interaction with the exchange factors GrpE and Bag-1.

PMID- 11323719
TI  - Gal repressosome contains an antiparallel DNA loop.
AB  - Gal repressosome assembly and repression of the gal operon in Escherichia coli
      occurs when two dimeric GalR proteins and the histone-like HU protein bind to
      cognate sites causing DNA looping. Structure-based genetic analysis defined the
      GalR surfaces interacting to form a stacked, V-shaped, tetrameric structure.
      Stereochemical models of the four possible DNA loops compatible with the GalR
      tetramer configuration were constructed using the sequence-dependent structural
      parameters of the interoperator DNA and conformation changes caused by GalR and
      asymmetric HU binding. Evaluation of their DNA elastic energies gave unambiguous
      preference to a loop structure in which the two gal operators adopt an
      antiparallel orientation causing undertwisting of DNA.

PMID- 11323720
TI  - The structure of the IgE Cepsilon2 domain and its role in stabilizing the complex
      with its high-affinity receptor FcepsilonRIalpha.
AB  - The stability of the complex between IgE and its high-affinity receptor,
      FcepsilonRI, on mast cells is a critical factor in the allergic response. The
      long half-life of the complex of IgE bound to this receptor in situ (
      approximately 2 weeks, compared with only hours for the comparable IgG complex)
      contributes to the permanent sensitization of these cells and, hence, to the
      immediate response to allergens. Here we show that the second constant domain of
      IgE, Cepsilon2, which takes the place of the flexible hinge in IgG, contributes
      to this long half-life. When the Cepsilon2 domain is deleted from the IgE Fc
      fragment, leaving only the Cepsilon3 and Cepsilon4 domains (Cepsilon3-4
      fragment), the rate of dissociation from the receptor is increased by greater
      than 1 order of magnitude. We report the structure of the Cepsilon2 domain by
      heteronuclear NMR spectroscopy and show by chemical shift perturbation that it
      interacts with FcepsilonRIalpha. By sedimentation equilibrium we show that the
      Cepsilon2 domain binds to the Cepsilon3-4 fragment of IgE. These interactions of
      Cepsilon2 with both FcepsilonRIalpha and Cepsilon3-4 provide a structural
      explanation for the exceptionally slow dissociation of the IgE-FcepsilonRIalpha
      complex.

PMID- 11323721
TI  - Carboxyl proteinase from Pseudomonas defines a novel family of subtilisin-like
      enzymes.
AB  - The crystal structure of a pepstatin-insensitive carboxyl proteinase from
      Pseudomonas sp. 101 (PSCP) has been solved by single-wavelength anomalous
      diffraction using the absorption peak of bromide anions. Structures of the
      uninhibited enzyme and of complexes with an inhibitor that was either covalently
      or noncovalently bound were refined at 1.0-1.4 A resolution. The structure of
      PSCP comprises a single compact domain with a diameter of approximately 55 A,
      consisting of a seven-stranded parallel beta-sheet flanked on both sides by a
      number of helices. The fold of PSCP is a superset of the subtilisin fold, and the
      covalently bound inhibitor is linked to the enzyme through a serine residue.
      Thus, the structure of PSCP defines a novel family of serine-carboxyl proteinases
      (defined as MEROPS S53) with a unique catalytic triad consisting of Glu 80, Asp
      84 and Ser 287.

PMID- 11323722
TI  - A helical lid converts a sulfotransferase to a dehydratase.
AB  - We report here the crystal structure of retinol dehydratase, an enzyme that
      catalyzes the synthesis of anhydroretinol. The enzyme is a member of the
      sulfotransferase superfamily and its crystal structure reveals the insertion of a
      helical lid into a canonical sulfotransferase fold. Site-directed mutations
      demonstrate that this inserted lid is necessary for anhydroretinol production but
      not for sulfonation; thus, insertion of a helical lid can convert a
      sulfotransferase into a dehydratase.

PMID- 11323723
TI  - Nonprolyl cis peptide bonds in unfolded proteins cause complex folding kinetics.
AB  - Folding of tendamistat, an inhibitor of alpha-amylase, is a fast two-state
      process accompanied by two minor slow reactions, which were assigned to prolyl
      isomerization. In a proline-free variant, 5% of the molecules still fold slowly
      with a rate constant of 2.5 s(-1). This reaction is caused by a slow equilibrium
      between two populations of unfolded molecules. The time constant for this
      equilibration process, its sensitivity to LiCl and its temperature dependence
      identify it as a cis-trans isomerization of nonprolyl peptide bonds. Although
      nonprolyl peptide bonds have the cis conformation populating only approximately
      0.15% in unfolded proteins, their large number generates a significant fraction
      of slow-folding molecules. This emphasizes that heterogeneous populations in an
      unfolded protein can induce complex folding kinetics on various time scales.

PMID- 11323724
TI  - Crystal structure of proteolytic fragments of the redox-sensitive Hsp33 with
      constitutive chaperone activity.
AB  - Heat shock protein 33 (Hsp33) inhibits aggregation of partially denatured
      proteins during oxidative stress. The chaperone activity of Hsp33 is unique among
      heat shock proteins because the activity is reversibly regulated by cellular
      redox status. We report here the crystal structure of the N-terminal region of
      Hsp33 fragments with constitutive chaperone activity. The structure reveals that
      the N-terminal portion of Hsp33 forms a tightly associated dimer formed by a
      domain crossover. A concave groove on the dimeric surface contains an elongated
      hydrophobic patch that could potentially bind denatured protein substrates. The
      termini of the subunits are located near the hydrophobic patch, indicating that
      the cleaved C-terminal domain may shield the hydrophobic patch in an inactive
      state. Two of the four conserved zinc-coordinating cysteines are in the end of
      the N-terminal domain, and the other two are in the cleaved C-terminal domain.
      The structural information and subsequent biochemical characterizations suggest
      that the redox switch of Hsp33 occurs by a reversible dissociation of the C
      terminal regulatory domain through oxidation of zinc-coordinating cysteines and
      zinc release.

PMID- 11323725
TI  - The structure of ADP-ribose pyrophosphatase reveals the structural basis for the
      versatility of the Nudix family.
AB  - Regulation of cellular levels of ADP-ribose is important in preventing
      nonenzymatic ADP-ribosylation of proteins. The Escherichia coli ADP-ribose
      pyrophosphatase, a Nudix enzyme, catalyzes the hydrolysis of ADP-ribose to ribose
      5-P and AMP, compounds that can be recycled as part of nucleotide metabolism. The
      structures of the apo enzyme, the active enzyme and the complex with ADP-ribose
      were determined to 1.9 A, 2.7 A and 2.3 A, respectively. The structures reveal a
      symmetric homodimer with two equivalent catalytic sites, each formed by residues
      of both monomers, requiring dimerization through domain swapping for substrate
      recognition and catalytic activity. The structures also suggest a role for the
      residues conserved in each Nudix subfamily. The Nudix motif residues, folded as a
      loop-helix-loop tailored for pyrophosphate hydrolysis, compose the catalytic
      center; residues conferring substrate specificity occur in regions of the
      sequence removed from the Nudix motif. This segregation of catalytic and
      recognition roles provides versatility to the Nudix family.

PMID- 11323729
TI  - Fluvoxamine for the treatment of anxiety disorders in children and adolescents.
      The Research Unit on Pediatric Psychopharmacology Anxiety Study Group.
AB  - BACKGROUND: Drugs that selectively inhibit serotonin reuptake are effective
      treatments for adults with mood and anxiety disorders, but limited data are
      available on the safety and efficacy of serotonin-reuptake inhibitors in children
      with anxiety disorders. METHODS: We studied 128 children who were 6 to 17 years
      of age; who met the criteria for social phobia, separation anxiety disorder, or
      generalized anxiety disorder; and who had received psychological treatment for
      three weeks without improvement. The children were randomly assigned to receive
      fluvoxamine (at a maximum of 300 mg per day) or placebo for eight weeks and were
      evaluated with rating scales designed to assess the degree of anxiety and
      impairment. RESULTS: Children in the fluvoxamine group had a mean (+/-SD)
      decrease of 9.7+/-6.9 points in symptoms of anxiety on the Pediatric Anxiety
      Rating Scale (range of possible scores, 0 to 25, with higher scores indicating
      greater anxiety), as compared with a decrease of 3.1+/-4.8 points among children
      in the placebo group (P<0.001). On the Clinical Global Impressions-Improvement
      scale, 48 of 63 children in the fluvoxamine group (76 percent) responded to the
      treatment, as indicated by a score of less than 4, as compared with 19 of 65
      children in the placebo group (29 percent, P<0.001). Five children in the
      fluvoxamine group (8 percent) discontinued treatment because of adverse events,
      as compared with one child in the placebo group (2 percent). CONCLUSIONS:
      Fluvoxamine is an effective treatment for children and adolescents with social
      phobia, separation anxiety disorder, or generalized anxiety disorder.

PMID- 11323730
TI  - Effects of chlorthalidone and diltiazem on myocardial ischemia in elderly
      patients with hypertension and coronary artery disease.
AB  - OBJECTIVE: Antihypertensive therapy with thiazides decreases coronary events in
      elderly patients. However, the influence of diuretics on myocardial ischemia has
      not been fully investigated. The aim of this study was to compare the effect of
      chlorthalidone and diltiazem on myocardial ischemia. METHODS: Following a
      randomized, double-blind, crossover protocol, we studied 15 elderly hypertensive
      patients aged 73.6+/-4.6 years with myocardial ischemia. All patients had
      angiographically documented coronary artery disease. We measured patients using
      48- hour ambulatory electrocardiogram monitoring and exercise testing. After a 2
      week period using placebo, patients received chlorthalidone or diltiazem for 4
      weeks. RESULTS: Both treatments lowered systolic and diastolic blood pressures.
      The number of ischemic episodes on ambulatory electrocardiogram recordings was
      reduced with the use of chlorthalidone (2.5+/-3.8) and diltiazem (3.2+/-4.2) when
      compared with placebo (7.9+/-8.8; p<0.05). The total duration of ischemic
      episodes was reduced in both treatments when compared with placebo
      (chlorthalidone: 19.2+/-31.9min; diltiazem: 19.3+/-29.6min; placebo: 46.1+/
      55.3min; p<0.05). CONCLUSION: In elderly hypertensive patients with coronary
      artery disease, chlorthalidone reduced myocardial ischemia similarly to
      diltiazem. This result is consistent with epidemiological studies and suggests
      that reduction of arterial blood pressure with thiazide therapy plays an
      important role in decreasing myocardial ischemia.

PMID- 11323731
TI  - Exercise stress testing in healthy subjects during cholinergic stimulation after
      a single dose of pyridostigmine.
AB  - OBJECTIVE: The evaluation, by exercise stress testing, of the cardiorespiratory
      effects of pyridostigmine (PYR), a reversible acetylcholinesterase inhibitor.
      METHODS: A double-blind, randomized, cross-over, placebo-controlled comparison of
      hemodynamic and ventilation variables of 10 healthy subjects who underwent three
      exercise stress tests (the first for adaptation and determination of tolerance to
      exercise, the other two after administration of placebo or 45mg of PYR). RESULTS:
      Heart rate at rest was: 68+/-3 vs 68+/-3bpm before and after placebo,
      respectively (P=0.38); 70+/-2 vs 59+/-2bpm, before and after pyridostigmine,
      respectively (P<0.01). During exercise, relative to placebo: a significantly
      lower heart rate after PYR at, respectively, 20% (P=0.02), 40% (P=0.03), 80%
      (P=0.05) and 100% (P=0.02) of peak effort was observed. No significant
      differences were observed in arterial blood pressure, oxygen consumption at
      submaximal and maximal effort, exercise duration, respiratory ratio, CO2
      production, ventilation threshold, minute ventilation, and oxygen pulse.
      CONCLUSION: Pyridostigmine, at a dose of 45mg, decreases heart rate at rest and
      during exercise, with minimal side effects and without interfering with exercise
      tolerance and ventilation variables.

PMID- 11323732
TI  - Bundle branch and atrioventricular block as complications of acute myocardial
      infarction in the thrombolytic era.
AB  - OBJECTIVE: To analyze the incidence of intraventricular and atrioventricular
      conduction defects associated with acute myocardial infarction and the degree of
      in hospital mortality resulting from this condition during the era of
      thrombolytic therapy. METHODS: Observational study of a cohort of 929 consecutive
      patients with acute myocardial infarction. Multivariate analysis by logistic
      regression. Was used. RESULTS: Logistic regression showed a greater incidence of
      bundle branch block in male sex (odds ratio = 1.87, 95% CI = 1.02-3.42), age over
      70 years (odds ratio = 2.31, 95% CI = 1.68-5.00), anterior localization of the
      infarction (odds ratio = 1.93, 95% CI = 1.03-3.65). There was a greater incidence
      of complete atrioventricular block in inferior infarcts (odds ratio = 2.59, 95%
      CI 1.30-5.18) and the presence of cardiogenic shock (odds ratio = 3.90, 95% CI =
      1.43-10.65). Use of a thrombolytic agent was associated with a tendency toward a
      lower occurrence of bundle branch block (odds ratio = 0.68) and a greater
      occurrence of complete atrioventricular block (odds ratio = 1.44). The presence
      of bundle branch block (odds ratio = 2.45 95%, CI = 1.14-5.28) and of complete
      atrioventricular block (odds ratio = 13.59, 95% CI = 5.43-33.98) was associated
      with a high and independent probability of inhospital death. CONCLUSION: During
      the current era of thrombolytic therapy and in this population, intraventricular
      disturbances of electrical conduction and complete atrioventricular block were
      associated with a high and independent risk of inhospital death during acute
      myocardial infarction.

PMID- 11323733
TI  - Reliability of the information about the history of diagnosis and treatment of
      hypertension. Differences in regard to sex, age, and educational level. The Pro
      Saude study.
AB  - OBJECTIVE: To assess the intraobserver reliability of the information about the
      history of diagnosis and treatment of hypertension. METHODS: A multidimensional
      health questionnaire, which was filled out by the interviewees, was applied twice
      with an interval of 2 weeks, in July '99, to 192 employees of the University of
      the State of Rio de Janeiro (UERJ), stratified by sex, age, and educational
      level. The intraobserver reliability of the answers provided was estimated by the
      kappa statistic and by the coefficient of intraclass correlation (CICC). RESULTS:
      The general kappa (k) statistic was 0.75 (95% CI=0.73-0.77). Reliability was
      higher among females (k=0.88, 95% CI=0.85-0.91) than among males (k=0.62, 95%
      CI=0.59-0.65). The reliability was higher among individuals 40 years of age or
      older (k=0.79; 95% CI=0.73-0.84) than those from 18 to 39 years (k=0.52; 95%
      CI=0.45-0.57). Finally, the kappa statistic was higher among individuals with a
      university educational level (k=0.86; 95% CI=0.81-0.91) than among those with
      high school educational level (k=0.61; 95% CI=0.53-0.70) or those with middle
      school educational level (k=0.68; 95% CI=0.64-0.72). The coefficient of
      intraclass correlation estimated by the intraobserver agreement in regard to age
      at the time of the diagnosis of hypertension was 0.74. A perfect agreement
      between the 2 answers (k=1.00) was observed for 22 interviewees who reported
      prior prescription of antihypertensive medication. CONCLUSION: In the population
      studied, estimates of the reliability of the history of medical diagnosis of
      hypertension and its treatment ranged from substantial to almost perfect
      reliability.

PMID- 11323734
TI  - Use of automated external defibrillators in a Brazilian airline. A 1-year
      experience.
AB  - After the incorporation of automated external defibrillators by other airlines
      and the support of the Brazilian Society of Cardiology, Varig Airlines began the
      onboard defibrillation program with the initial purpose of equipping wide-body
      aircrafts frequently used in international flights and that airplanes use in the
      Rio - Sao Paulo route. With all flight attendants trained, the automated external
      defibrillation devices were incorporated to 34 airplanes of a total fleet of 80
      aircrafts. The devices were installed in the baggage compartments secured with
      velcro straps and 2 pairs of electrodes, one or which pre-connected to the device
      to minimize application time. Later, a portable monitor was address to the
      resuscitation kit in the long flights. The expansion of the knowledge of the
      basic life support fundamentors and the corrected implantation of the survival
      chain and of the automated external defibrillators will increase the extense of
      recovery of cardiorespiratory arrest victims in aircrafts.

PMID- 11323735
TI  - Pneumococcal endocarditis of subacute evolution.
AB  - With the development of penicillin, Streptococcus pneumoniae has become an
      uncommon cause of bacterial endocarditis in adults. Subacute manifestation of
      pneumococcal endocarditis has been reported a few times in the literature, but
      most reports define the disease as acute, severe, and having a high mortality
      rate. We report the case of a 58-year-old male with subacute bacterial
      endocarditis due to Streptococcus pneumoniae. We stress the low frequency of this
      agent as a cause of endocarditis and the atypical evolution of this case. The
      pathophysiology, clinical manifestations and evolution, and the therapeutical
      options for this type of infection are also discussed.

PMID- 11323736
TI  - Surgical repair of a pseudoaneurysm of the ascending aorta after aortic valve
      replacement.
AB  - We report the case of a patient with a pseudoaneurysm of the ascending aortic
      clinically diagnosed 5 months after surgical replacement of the aortic valve.
      Diagnosis was confirmed with the aid of two-dimensional echocardiography and
      helicoidal angiotomography. The corrective surgery, which consisted of a
      reinforced suture of the communication with the ascending aorta after opening and
      aspiration of the cavity of the pseudoaneurysm, was successfully performed
      through a complete sternotomy using extracorporeal circulation, femorofemoral
      cannulation, and moderate hypothermia, with no aortic clamping.

PMID- 11323737
TI  - An 18-year-old male with dyspnea and pulmonary arterial hypertension.

PMID- 11323738
TI  - [Clinic-radiographic correlation. Case 4/2001 - Instituto do Coracao do Hospital
      das Clinicas da FMUSP].

PMID- 11323739
TI  - Application of the principles of evidence-based medicine in programs to assess
      high-cost procedures and medications.

PMID- 11323740
TI  - [Rheumatic heart valve disease].

PMID- 11323741
TI  - Mechanisms in anti-inflammation and resolution: the role of lipoxins and aspirin
      triggered lipoxins.
AB  - Multicellular host responses to infection, injury or inflammatory stimuli lead to
      the formation of a broad range of chemical mediators by the host. The integrated
      response of the host is essential to health and disease; thus it is important to
      achieve a more complete understanding of the molecular and cellular events
      governing the formation and actions of endogenous mediators of resolution that
      appear to control the duration of inflammation. Lipoxins are trihydroxytetraene
      containing lipid mediators that can be formed during cell-cell interactions and
      are predominantly counterregulators of some well-known mediators of inflammation.
      Since this circuit of lipoxin formation and action appears to be of physiological
      relevance for the resolution of inflammation, therapeutic modalities targeted at
      this system are likely to have fewer unwanted side effects than other candidates
      and current anti-inflammatory therapies. Here, we present an overview of the
      recent knowledge about the biosynthesis and bioactions of these anti-inflammatory
      lipid mediators.

PMID- 11323742
TI  - Metabolite and light regulation of metabolism in plants: lessons from the study
      of a single biochemical pathway.
AB  - We are using molecular, biochemical, and genetic approaches to study the
      structural and regulatory genes controlling the assimilation of inorganic
      nitrogen into the amino acids glutamine, glutamate, aspartate and asparagine.
      These amino acids serve as the principal nitrogen-transport amino acids in most
      crop and higher plants including Arabidopsis thaliana. We have begun to
      investigate the regulatory mechanisms controlling nitrogen assimilation into
      these amino acids in plants using molecular and genetic approaches in
      Arabidopsis. The synthesis of the amide amino acids glutamine and asparagine is
      subject to tight regulation in response to environmental factors such as light
      and to metabolic factors such as sucrose and amino acids. For instance, light
      induces the expression of glutamine synthetase (GLN2) and represses expression of
      asparagine synthetase (ASN1) genes. This reciprocal regulation of GLN2 and ASN1
      genes by light is reflected at the level of transcription and at the level of
      glutamine and asparagine biosynthesis. Moreover, we have shown that the
      regulation of these genes is also reciprocally controlled by both organic
      nitrogen and carbon metabolites. We have recently used a reverse genetic approach
      to study putative components of such metabolic sensing mechanisms in plants that
      may be conserved in evolution. These components include an Arabidopsis homolog
      for a glutamate receptor gene originally found in animal systems and a plant PII
      gene, which is a homolog of a component of the bacterial Ntr system. Based on our
      observations on the biology of both structural and regulatory genes of the
      nitrogen assimilatory pathway, we have developed a model for metabolic control of
      the genes involved in the nitrogen assimilatory pathway in plants.

PMID- 11323743
TI  - Extracellular calcium-sensing receptor: structural and functional features and
      association with diseases.
AB  - The recently cloned extracellular calcium-sensing receptor (CaR) is a G protein
      coupled receptor that plays an essential role in the regulation of extracellular
      calcium homeostasis. This receptor is expressed in all tissues related to this
      control (parathyroid glands, thyroid C-cells, kidneys, intestine and bones) and
      also in tissues with apparently no role in the maintenance of extracellular
      calcium levels, such as brain, skin and pancreas. The CaR amino acid sequence is
      compatible with three major domains: a long and hydrophilic aminoterminal
      extracellular domain, where most of the activating and inactivating mutations
      described to date are located and where the dimerization process occurs, and the
      agonist-binding site is located, a hydrophobic transmembrane domain involved in
      the signal transduction mechanism from the extracellular domain to its respective
      G protein, and a carboxyterminal intracellular tail, with a well-established role
      for cell surface CaR expression and for signal transduction. CaR cloning was
      immediately followed by the association of genetic human diseases with
      inactivating and activating CaR mutations: familial hypocalciuric hypercalcemia
      and neonatal severe hyperparathyroidism are caused by CaR-inactivating mutations,
      whereas autosomal dominant hypoparathyroidism is secondary to CaR-activating
      mutations. Finally, we will comment on the development of drugs that modulate CaR
      function by either activating (calcimimetic drugs) or antagonizing it (calcilytic
      drugs), and on their potential therapeutic implications, such as medical control
      of specific cases of primary and uremic hyperparathyroidism with calcimimetic
      drugs and a potential treatment for osteoporosis with a calcilytic drug.

PMID- 11323744
TI  - Insights into the physiological function of cellular prion protein.
AB  - Prions have been extensively studied since they represent a new class of
      infectious agents in which a protein, PrPsc (prion scrapie), appears to be the
      sole component of the infectious particle. They are responsible for transmissible
      spongiform encephalopathies, which affect both humans and animals. The mechanism
      of disease propagation is well understood and involves the interaction of PrPsc
      with its cellular isoform (PrPc) and subsequently abnormal structural conversion
      of the latter. PrPc is a glycoprotein anchored on the cell surface by a
      glycosylphosphatidylinositol moiety and expressed in most cell types but mainly
      in neurons. Prion diseases have been associated with the accumulation of the
      abnormally folded protein and its neurotoxic effects; however, it is not known if
      PrPc loss of function is an important component. New efforts are addressing this
      question and trying to characterize the physiological function of PrPc. At least
      four different mouse strains in which the PrP gene was ablated were generated and
      the results regarding their phenotype are controversial. Localization of PrPc on
      the cell membrane makes it a potential candidate for a ligand uptake, cell
      adhesion and recognition molecule or a membrane signaling molecule. Recent data
      have shown a potential role for PrPc in the metabolism of copper and moreover
      that this metal stimulates PrPc endocytosis. Our group has recently demonstrated
      that PrPc is a high affinity laminin ligand and that this interaction mediates
      neuronal cell adhesion and neurite extension and maintenance. Moreover, PrPc
      caveolin-1 dependent coupling seems to trigger the tyrosine kinase Fyn
      activation. These data provide the first evidence for PrPc involvement in signal
      transduction.

PMID- 11323745
TI  - Interactions of laminin with the amyloid beta peptide. Implications for
      Alzheimer's disease.
AB  - Extensive neuronal cell loss is observed in Alzheimer's disease. Laminin
      immunoreactivity colocalizes with senile plaques, the characteristic
      extracellular histopathological lesions of Alzheimer brain, which consist of the
      amyloid beta (A(beta)) peptide polymerized into amyloid fibrils. These lesions
      have neurotoxic effects and have been proposed to be a main cause of
      neurodegeneration. In order to understand the pathological significance of the
      interaction between laminin and amyloid, we investigated the effect of laminin on
      amyloid structure and toxicity. We found that laminin interacts with the A(beta)1
      40 peptide, blocking fibril formation and even inducing depolymerization of
      preformed fibrils. Protofilaments known to be intermediate species of A(beta)
      fibril formation were also detected as intermediate species of laminin-induced
      A(beta) fibril depolymerization. Moreover, laminin-amyloid interactions inhibited
      the toxic effects on rat primary hippocampal neurons. As a whole, our results
      indicate a putative anti-amyloidogenic role of laminin which may be of biological
      and therapeutic interest for controlling amyloidosis, such as those observed in
      cerebral angiopathy and Alzheimer's disease.

PMID- 11323746
TI  - The extracellular matrix in multiple sclerosis: an update.
AB  - Extracellular matrix (ECM) molecules play important roles in the pathobiology of
      the major human central nervous system (CNS) inflammatory/demyelinating disease
      multiple sclerosis (MS). This mini-review highlights some recent work on CNS
      endothelial cell interactions with vascular basement membrane ECM as part of the
      cellular immune response, and roles for white matter ECM molecules in
      demyelination and remyelination in MS lesions. Recent basic and clinical
      investigations of MS emphasize axonal injury, not only in chronic MS plaques, but
      also in acute lesions; progressive axonal degeneration in normal-appearing white
      matter also may contribute to brain and spinal cord atrophy in MS patients.
      Remodeling of the interstitial white matter ECM molecules that affect axon
      regeneration, however, is incompletely characterized. Our ongoing
      immunohistochemical studies demonstrate enhanced ECM versican, a neurite and axon
      growth-inhibiting white matter ECM proteoglycan, and dermatan sulfate
      proteoglycans at the edges of inflammatory MS lesions. This suggests that
      enhanced proteoglycan deposition in the ECM and axonal growth inhibition may
      occur early and are involved in expansion of active lesions. Decreased ECM
      proteoglycans and their phagocytosis by macrophages along with myelin in plaque
      centers imply that there is "injury" to the ECM itself. These results indicate
      that white matter ECM proteoglycan alterations are integral to MS pathology at
      all disease stages and that they contribute to a CNS ECM that is inhospitable to
      axon regrowth/regeneration.

PMID- 11323747
TI  - Cross-talk between neurons and glia: highlights on soluble factors.
AB  - The development of the nervous system is guided by a balanced action between
      intrinsic factors represented by the genetic program and epigenetic factors
      characterized by cell-cell interactions which neural cells might perform
      throughout nervous system morphogenesis. Highly relevant among them are neuron
      glia interactions. Several soluble factors secreted by either glial or neuronal
      cells have been implicated in the mutual influence these cells exert on each
      other. In this review, we will focus our attention on recent advances in the
      understanding of the role of glial and neuronal trophic factors in nervous system
      development. We will argue that the functional architecture of the brain depends
      on an intimate neuron-glia partnership.

PMID- 11323748
TI  - A fucan from the brown seaweed Spatoglossum schroederi inhibits Chinese hamster
      ovary cell adhesion to several extracellular matrix proteins.
AB  - Fucans, a family of sulfated polysaccharides present in brown seaweed, have
      several biological activities. Their use as drugs would offer the advantage of no
      potential risk of contamination with viruses or particles such as prions. A fucan
      prepared from Spatoglossum schroederi was tested as a possible inhibitor of cell
      matrix interactions using wild-type Chinese hamster ovary cells (CHO-K1) and the
      mutant type deficient in xylosyltransferase (CHO-745). The effect of this polymer
      on adhesion properties with specific extracellular matrix components was studied
      using several matrix proteins as substrates for cell attachment. Treatment with
      the polymer inhibited the adhesion of fibronectin to both CHO-K1 (2 x 10(5)) and
      CHO-745 (2 x 10(5) and 5 x 10(5)) cells. No effect was detected with laminin,
      using the two cell types. On the other hand, adhesion to vitronectin was
      inhibited in CHO-K1 cells and adhesion to type I collagen was inhibited in CHO
      745 cells. In spite of this inhibition, the fucan did not affect either cell
      proliferation or cell cycle. These results demonstrate that this polymer is a new
      anti-adhesive compound with potential pharmacological applications.

PMID- 11323749
TI  - Inhibition of in vitro CO2 production and lipid synthesis by 2-hydroxybutyric
      acid in rat brain.
AB  - 2-Hydroxybutyric acid appears at high concentrations in situations related to
      deficient energy metabolism (e.g., birth asphyxia) and also in inherited
      metabolic diseases affecting the central nervous system during neonatal
      development, such as "cerebral" lactic acidosis, glutaric aciduria type II,
      dihydrolipoyl dehydrogenase (E3) deficiency, and propionic acidemia. The present
      study was carried out to determine the effect of 2-hydroxybutyric acid at various
      concentrations (1-10 mM) on CO2 production and lipid synthesis from labeled
      substrates in cerebral cortex of 30-day-old Wistar rats in vitro. CO2 production
      was significantly inhibited (30-70%) by 2-hydroxybutyric acid in cerebral cortex
      prisms, in total homogenates and in the mitochondrial fraction. We also
      demonstrated a significant inhibition of lipid synthesis (20-45%) in cerebral
      cortex prisms and total homogenates in the presence of 2-hydroxybutyric acid.
      However, no inhibition of lipid synthesis occurred in homogenates free of nuclei
      and mitochondria. The results indicate an impairment of mitochondrial energy
      metabolism caused by 2-hydroxybutyric acid, a fact that may secondarily lead to
      reduction of lipid synthesis. It is possible that these findings may be
      associated with the neuropathophysiology of the situations where 2-hydroxybutyric
      acid is accumulated.

PMID- 11323750
TI  - Galactosaminoglycans from normal myometrium and leiomyoma.
AB  - In many tumors, the amount of chondroitin sulfate in the extracellular matrix has
      been shown to be elevated when compared to the corresponding normal tissue.
      Nevertheless, the degree of chondroitin sulfate increase varies widely. In order
      to investigate a possible correlation between the amount of chondroitin sulfate
      and tumor size, several individual specimens of human leiomyoma, a benign uterine
      tumor, were analyzed. The glycosaminoglycans from eight tumors were extracted and
      compared with those from the respective adjacent normal myometrium. The main
      glycosaminoglycan found in normal myometrium was dermatan sulfate, with small
      amounts of chondroitin sulfate and heparan sulfate. In leiomyoma, both dermatan
      sulfate and chondroitin sulfate were detected and the total amounts of the two
      galactosaminoglycans was increased in all tumors when compared to normal tissue.
      In contrast, the heparan sulfate concentration decreased in the tumor. To assess
      the disaccharide composition of galactosaminoglycans, these compounds were
      incubated with bacterial chondroitinases AC and ABC. The amounts of L-iduronic
      acid-containing disaccharides remained constant, whereas the concentration of D
      glucuronic acid-containing disaccharides increased from 2 to 10 times in the
      tumor, indicating that D-glucuronic acid-containing disaccharides are responsible
      for the elevation in galactosaminoglycan concentration. This increase is
      positively correlated with tumor size.

PMID- 11323751
TI  - Effects of formaldehyde on the frog's mucociliary epithelium as a surrogate to
      evaluate air pollution effects on the respiratory epithelium.
AB  - The increasing use of alcohol as an alternative fuel to gasoline or diesel can
      increase emission of formaldehyde, an organic gas that is irritant to the mucous
      membranes. The respiratory system is the major target of air pollutants and its
      major defense mechanism depends on the continuous activity of the cilia and the
      resulting constant transportation of mucous secretion. The present study was
      designed to evaluate the effects of formaldehyde on the ciliated epithelium
      through a relative large dose range around the threshold limit value adopted by
      the Brazilian legislation, namely 1.6 ppm (1.25 to 5 ppm). For this purpose, the
      isolated frog palate preparation was used as the target of toxic injury. Four
      groups of frog palates were exposed to diluted Ringer solution (control, N = 8)
      and formaldehyde diluted in Ringer solution at three different concentrations
      (1.25, 2.5 and 5.0 ppm, N = 10 for each group). Mucociliary clearance and ciliary
      beat frequency decreased significantly in contact with formaldehyde at the
      concentrations of 2.5 and 5.0 ppm after 60 min of exposure (P<0.05). We conclude
      that relatively low concentrations of formaldehyde, which is even below the
      Brazilian threshold limit value, are sufficient to cause short-term mucociliary
      impairment.

PMID- 11323752
TI  - Effect of dietary (n-3) highly unsaturated fatty acids on growth and survival of
      fat snook (Centropomus parallelus, Pisces: Centropomidae) larvae during first
      feeding.
AB  - The effect of rotifers, Brachionus rotundiformis (S-type), fed three different
      diets: A (rotifer fed Nannochloropsis oculata), B (rotifer fed N. oculata and
      baker's yeast, 1:1), and C (rotifer fed N. oculata and baker's yeast, 1:1, and
      enriched with Selcoregister mark or target), was evaluated based on the survival,
      growth and swim bladder inflation rate of fat snook larvae. Rotifers of treatment
      A had higher levels (4.58 mg/g dry weight) of eicosapentaenoic acid (EPA) than B
      (1.81 mg/g dry weight), and similar levels (0.04 and 0.06 mg/g dry weight,
      respectively) of docosahexaenoic acid (DHA). Rotifers of treatment C had the
      highest levels of EPA (13.2 mg/g dry weight) and DHA (6.08 mg/g dry weight). Fat
      snook eggs were obtained by spawning induction with human chorionic gonadotropin.
      Thirty hours after hatching, 30 larvae/liter were stocked in black cylindric
      conical tanks (36-liter capacity). After 14 days of culture, there were no
      significant differences among treatments. Mean standard length was 3.13 mm for
      treatment A, 3.17 mm for B, and 3.39 mm for C. Mean survival rates were very low
      (2.7% for treatment A, 2.3% for B, and 1.8% for C). Swim bladder inflation rates
      were 34.7% for treatment A, 27.1% for B, and 11.9% for C. The lack of differences
      in growth and survival among treatments showed that the improvement of the
      dietary value of rotifer may not have been sufficient to solve the problem of
      larval rearing. Some other factor, probably pertaining to the quality of the
      larvae, may have negatively influenced survival.

PMID- 11323753
TI  - Functional differences between two morphologically distinct cell subpopulations
      within a human colorectal carcinoma cell line.
AB  - The LISP-I human colorectal adenocarcinoma cell line was isolated from a hepatic
      metastasis at the Ludwig Institute, Sao Paulo, SP, Brazil. The objective of the
      present study was to isolate morphologically different subpopulations within the
      LISP-I cell line, and characterize some of their behavioral aspects such as
      adhesion to and migration towards extracellular matrix components, expression of
      intercellular adhesion molecules and tumorigenicity in vitro. Once isolated, the
      subpopulations were submitted to adhesion and migration assays on laminin and
      fibronectin (crucial proteins to invasion and metastasis), as well as to
      anchorage-independent growth. Two morphologically different subpopulations were
      isolated: LISP-A10 and LISP-E11. LISP-A10 presents a differentiated epithelial
      pattern, and LISP-E11 is fibroblastoid, suggesting a poorly differentiated
      pattern. LISP-A10 expressed the two intercellular adhesion molecules tested,
      carcinoembryonic antigen (CEA) and desmoglein, while LISP-E11 expressed only low
      amounts of CEA. On the other hand, adhesion to laminin and fibronectin as well as
      migration towards these extracellular matrix proteins were higher in LISP-E11, as
      expected from its poorly differentiated phenotype. Both subpopulations showed
      anchorage-independent growth on a semi-solid substrate. These results raise the
      possibility that the heterogeneity found in the LISP-I cell line, which might
      have contributed to its ability to metastasize, was due to at least two different
      subpopulations herein identified.

PMID- 11323754
TI  - N-terminal amino acids of bovine alpha interferons are relevant for the
      neutralization of their antiviral activity.
AB  - The structure-function relationship of interferons (IFNs) has been studied by
      epitope mapping. Epitopes of bovine IFNs, however, are practically unknown,
      despite their importance in virus infections and in the maternal recognition of
      pregnancy. It has been shown that recombinant bovine (rBo)IFN-alphaC and rBoIFN
      alpha1 differ only in 12 amino acids and that the F12 monoclonal antibody (mAb)
      binds to a linear sequence of residues 10 to 34. We show here that the antiviral
      activities of these two IFNs were neutralized by the F12 mAb to different extents
      using two tests. In residual activity tests the antiviral activity dropped by
      more than 99% with rBoIFN-alphaC and by 84% with rBoIFN-alpha1. In checkerboard
      antibody titrations, the F12 mAb titer was 12,000 with rBoIFN-alphaC and only 600
      with rBoIFN-alpha1. Since these IFNs differ in their amino acid sequence at
      positions 11, 16 and 19 of the amino terminus, only these amino acids could
      account for the different neutralization titers, and they should participate in
      antibody binding. According to the three-dimensional structure described for
      human and murine IFNs, these amino acids are located in the alpha helix A; amino
      acids 16 and 19 of the bovine IFNs would be expected to be exposed and could bind
      to the antibody directly. The amino acid at position 11 forms a hydrogen bond in
      human IFNs-alpha and it is possible that, in bovine IFNs-alpha, the F12 mAb,
      binding near position 11, would disturb this hydrogen bond, resulting in the
      difference in the extent of neutralization observed.

PMID- 11323755
TI  - The 9-O-acetyl GD3 gangliosides are expressed by migrating chains of
      subventricular zone neurons in vitro.
AB  - Neurons from the anterior subventricular zone (SVZ) of the cerebral cortex
      migrate tangentially to become interneurons in the olfactory bulb during
      development and in adult rodents. This migration was defined as neuronophilic,
      independent of a radial glial substrate. The cortical SVZ and the rostral
      migratory stream to the olfactory bulb were shown to be rich in 9-O-acetyl GD3
      gangliosides (9-O-acGD3), which have been previously shown to be implicated in
      gliophilic migration in the rodent cerebral cortex and cerebellum. In the present
      study, we performed SVZ explant cultures using rats during their first postnatal
      week to analyze the expression of these gangliosides in chain migration of
      neuronal precursors. We characterized migrating chains of these neuroblasts
      through morphological analysis and immunocytochemistry for the neural cell
      adhesion molecule. By using the Jones monoclonal antibody which binds
      specifically to 9-O-acGD3 we showed that migrating chains from the SVZ explants
      express 9-O-acGD3 which is distributed in a punctate manner in individual cells.
      9-O-acGD3 is also present in migrating chains that form in the absence of radial
      glia, typical of the neuronophilic chain migration of the SVZ. Our data indicate
      that 9-O-acetylated gangliosides may participate in neuronophilic as well as
      gliophilic migration.

PMID- 11323756
TI  - Strain-dependent effects of diazepam and the 5-HT2B/2C receptor antagonist SB
      206553 in spontaneously hypertensive and Lewis rats tested in the elevated plus
      maze.
AB  - The 5-HT2B/2C receptor antagonist SB 206553 exerts anxiolytic effects in rat
      models of anxiety. However, these effects have been reported for standard rat
      strains, thus raising the issue of SB 206553 effects in rat strains displaying
      different levels of anxiety. Herein, the effects of SB 206553 in a 5-min elevated
      plus-maze test of anxiety were compared to those of the reference anxiolytic,
      diazepam, in two rat strains respectively displaying high (Lewis rats) and low
      (spontaneously hypertensive rats, SHR) anxiety. Diazepam (0.37, 0.75, or 1.5
      mg/kg; 30 min before testing) increased in a dose-dependent manner the behavioral
      measures in SHR, but not in Lewis rats. On the other hand, SB 206553 (1.25, 2.5,
      or 5 mg/kg; 30 min before testing) failed to alter the anxiety parameters in both
      strains, whereas it increased closed arm entries in Lewis rats, suggesting that
      it elicited hyperactivity in the latter strain. Accordingly, the hypolocomotor
      effect of the nonselective 5-HT2B/2C receptor agonist m-chlorophenylpiperazine
      (1.5 mg/kg ip 20 min before a 15-min exposure to an activity cage) was prevented
      by the 1.25 and 2.5 mg/kg doses of SB 206553 in Lewis rats and SHR, respectively.
      Compared with SHR, Lewis rats may display a lower response to benzodiazepine
      mediated effects and a more efficient control of locomotor activity by 5-HT2B/2C
      receptors.

PMID- 11323757
TI  - Regulation of antioxidant enzyme activities in male and female rat macrophages by
      sex steroids.
AB  - Human and animal immune functions present sex dimorphism that seems to be mainly
      regulated by sex hormones. In the present study, the activities of the
      antioxidant enzymes total superoxide dismutase (SOD), catalase (CAT), and
      glutathione peroxidase (GSH-Px) were measured in intraperitoneal resident
      macrophages from adult male and female rats. In addition to comparing males and
      females, we also examined the regulation of these enzyme activities in
      macrophages by sex steroids. GSH-Px activity did not differ between male and
      female macrophages. However, both total SOD and CAT activities were markedly
      higher in females than in males (83 and 180%). Removal of the gonads in both
      males and females (comparison between castrated groups) increased the difference
      in SOD activity from 83 to 138% and reduced the difference in CAT activity from
      180 to 86%. Castration and testosterone administration did not significantly
      modify the activities of the antioxidant enzymes in male macrophages. Ovariectomy
      did not affect SOD or GSH-Px activity but markedly reduced (48%) CAT activity.
      This latter change was fully reversed by estrogen administration, whereas
      progesterone had a smaller effect. These results led us to conclude that
      differences in the SOD and CAT activities may partially explain some of the
      differences in immune function reported for males and females. Also, estrogen is
      a potent regulator of CAT in macrophages and therefore this enzyme activity in
      macrophages may vary considerably during the menstrual cycle.

PMID- 11323759
TI  - Pathogenesis and presentation of common bile duct stones.
AB  - Common bile duct stones are generally classified as primary or secondary stones
      based on the locations of origin. The vast majority of the stones found in the
      biliary tree are secondary stones. The current review discusses the pathogenesis
      and presentations of primary and secondary biliary stones. Based on discussion of
      disease pathogenesis and presentation, recommendations for the evaluation and
      management of common and uncommon disease processes associated with
      choledocholithiasis are proposed.

PMID- 11323760
TI  - Advances in the imaging of common duct stones using magnetic resonance
      cholangiography, endoscopic ultrasonography, and laparoscopic ultrasonography.
AB  - Advances in magnetic resonance cholangiography (MRC) have resulted in
      consistently high sensitivity and specificity for the detection of common duct
      stones by MRC. There are multiple advantages to using MRC over endoscopic
      retrograde cholangiography (ERC) in the diagnosis of common duct stones, thereby
      reserving the use of ERC mainly as a therapeutic tool. Endoscopic ultrasonography
      has emerged as a modality capable of common duct stone detection and, when
      available, will compete with MRC and ERC for the diagnosis of common duct stones.
      However, its ability to image intrahepatic or proximal common duct stones would
      seem to be limited. Laparoscopic ultrasonography helps shorten operative time and
      costs less compared with intraoperative cholangiography. As more surgeons gather
      experience with laparoscopic ultrasonography and it becomes widely available, it
      has the promise to substitute for intraoperative cholangiography.

PMID- 11323761
TI  - Common bile duct stones: the role of preoperative, intraoperative, and
      postoperative ERCP.
AB  - The indications for endoscopic retrograde cholangiopancreatography (ERCP) to
      demonstrate the presence of common bile duct stones has changed in the era of
      laparoscopic cholecystectomy. Preoperative ERCP is indicated when there is strong
      evidence of common bile duct stones, ie, jaundice, cholangitis, ultrasound
      demonstration of a common bile duct stone, and specific enzyme elevations.
      Preoperative ERCP is not indicated in mild gallstone pancreatitis. ERCP and
      endoscopic sphincterotomy as the only treatment regimen is successful in elderly
      patients with severe comorbid illness who have gallstones and common bile duct
      stones. Intraoperative ERCP does not play a role in the era of laparoscopic
      cholecystectomy. Transcystic common duct stone removal or laparoscopic
      choledochotomy is becoming the approach to common duct stones demonstrated by
      intraoperative cholangiography. Postoperative ERCP is indicated when
      intraoperative removal of common bile duct stones is unsuccessful. It is
      important to note that magnetic resonance cholangiography will play an increasing
      role and will reduce the indications and frequency of the use of ERCP.

PMID- 11323762
TI  - Ductal stones: pathology, clinical manifestations, laparoscopic extraction
      techniques, and complications.
AB  - Laparoscopic treatment of ductal calculi in experienced hands is more successful
      and incurs a shorter hospital stay and overall costs than current orthodox two
      stage management (endoscopic stone extraction followed by cholecystectomy). The
      results of large series of laparoscopic ductal stone clearance report a median
      success rate of 90%, a mortality under 1%, and a missed stone rate of 0.8% to 4%.
      Thus the case for routine preoperative endoscopic stone extraction is no longer
      sustainable and this management option should be reserved for patients with
      cholangitis, severe gallstone-associated pancreatitis, and for patients
      considered unfit for surgery and general anesthesia. The remaining issues concern
      standardization of the techniques of laparoscopic ductal stone extraction and the
      intraoperative management algorithm with agreed indications for transcystic
      extraction versus direct common bile duct (CBD) exploration. Narrowed bile ducts
      should not be explored directly, and if the transcystic laparoscopic approach
      fails in these cases, endoscopic extraction is the safest option, either at the
      time of surgery under the same anesthetic or during the postoperative period. The
      insertion of a T-tube after direct common duct exploration detracts considerably
      from the benefits of the laparoscopic approach, and primary closure with either a
      cystic duct drainage cannula or by means of a temporary endobiliary stent is
      recommended.

PMID- 11323763
TI  - Technical considerations and laparoscopic bile duct exploration: transcystic and
      choledochotomy.
AB  - Single-stage laparoscopic treatment of gallstones and common bile duct (CBD)
      stones is now challenging the traditional two-stage endo/laparoscopic approach.
      Many surgeons are reluctant to adopt this procedure because they believe this
      operation to be difficult and time-consuming. The aim of this report is to
      describe the technical details of the procedure and to demonstrate its
      effectiveness in a large series of unselected, consecutive patients. CBD stones
      were demonstrated in 301 unselected patients out of 2,894 undergoing laparoscopic
      cholecystectomy (10.4%) and were treated laparoscopically in 297 (98.6%), by the
      transcystic route in 185 patients (62.2%) and after choledochotomy in 112
      patients (37.8%). Mean operative time was 119.2 minutes. Major complications were
      bile leakage (5 patients) and hemoperitoneum (4 patients) (3%). Retained CBD
      stones were observed in 14 patients (4.7%) and mortality in 1 high-risk patient
      (0.3%). Recurrent ductal stones occurred in 5 cases (1.6%) with dilated bile
      ducts, all after laparoscopic choledochotomy. Single-stage laparoscopic treatment
      of gallstones and CBD stones treats 2 problems during the same operation, avoids
      the additive complications of a second procedure (endoscopic sphincterotomy), and
      reduces hospital stay and costs. Laparoscopic management of ductal stones during
      laparoscopic cholecystectomy is the new "gold standard" for the treatment of
      gallstones and CBD stones.

PMID- 11323764
TI  - Prospective trials in laparoscopic bile duct exploration.
AB  - Laparoscopic exploration of the common bile duct (CBD) is performed either for
      the diagnosis or the treatment of CBD stones. Laparoscopic intraoperative
      cholangiography (IOC) versus ultrasonography (LUS) and laparoscopic versus
      endoscopic extraction of CBD stones were compared through a review of the
      prospective, comparative studies, randomized or not, evaluating these different
      techniques. Cystic duct cholangiography and fluoroscopic imaging are the
      standards for IOC. The potential protective effect of IOC regarding the risk or
      severity of CBD injuries might be the major argument for a routine use of
      laparoscopic IOC. Most if not all the purported advantages of LUS versus IOC for
      the diagnosis of CBD stones remain to be proven. Laparoscopic intraoperative
      diagnosis of CBD stones by cholangiography or ultrasonography followed by the
      laparoscopic extraction or, in case of failure, by postoperative endoscopic
      sphincterotomy, might represent the future for the diagnosis and treatment of CBD
      stones.

PMID- 11323765
TI  - Diagnostic and therapeutic choledochoscopy.
AB  - Laparoscopic cholecystectomy and common bile duct exploration are common surgical
      procedures for the general surgeon. To successfully remove common bile duct
      stones, choledochoscopy is an important technique for efficient and effective
      management. The choledochoscope can be introduced intraoperatively through the
      cystic duct or directly into the common bile duct and it also can be inserted
      transhepatically through a T-tube tract and per orally using a therapeutic
      duodenoscope. All of these methods allow for many options for the surgeon to
      consider, and one must be familiar with each of these techniques to maximize
      care. Successful stone extraction with the choledochoscope can be achieved in 75%
      to 95% of the cases with a morbidity less than 5%. Using this technique, the
      surgeon can improve the cost benefit of bile duct exploration.

PMID- 11323766
TI  - Intracorporeal lithotripsy in the management of biliary stone disease.
AB  - Choledocholithiasis accounts for approximately 4% to 10% of patients with biliary
      tract disease. The incidence of intrahepatic biliary disease is less common in
      the Western world and greater in Asian countries. The overwhelming majority of
      patients are treated by means of peroral endoscopy. In expert hands, standard
      techniques will clear the biliary tree from stones in approximately 90% of
      patients. However, 10% will require nonstandard management, including peroral or
      percutaneous mechanical, electrohydraulic, or laser lithotripsy. Very few
      patients will necessitate surgical intervention. Following is a review of the
      current status of intracorporeal lithotripsy, including principles and
      techniques, peroral and percutaneous applications, and its overall success.

PMID- 11323767
TI  - A cost analysis of the treatment of common bile duct stones discovered during
      cholecystectomy.
AB  - There are a variety of procedures to use once a common bile duct stone is
      discovered at the time of cholecystectomy. To be cost-effective, the surgeon must
      know how much money will be spent with each procedure chosen. Cost data is
      largely unavailable because costs are difficult to estimate and charge data are
      jealously guarded. In addition, costs are not the same at different hospitals and
      therefore cannot be compared. The factors that increase costs for treating bile
      duct stones are outlined in this report and real costs are used from one hospital
      to help with illustration. Surgical costs vary with the severity of the disease,
      the amount of operating room time required, and length of stay. These surgical
      costs can be avoided by choosing endoscopic retrograde cholangiopancreatography,
      but the new costs increase almost twice that of a successful laparoscopic common
      bile duct exploration. Knowledge of the pattern of choledocholithiasis, the
      varieties of treatment, the cost implications, and the outcomes of each are the
      subject of this report.

PMID- 11323768
TI  - Biomedical imaging: 2001 and beyond.

PMID- 11323769
TI  - Maps of the brain.
AB  - We review recent developments in brain mapping and computational anatomy that
      have greatly expanded our ability to analyze brain structure and function. The
      enormous diversity of brain maps and imaging methods has spurred the development
      of population-based digital brain atlases. These atlases store information on how
      the brain varies across age and gender, across time, in health and disease, and
      in large human populations. We describe how brain atlases, and the computational
      tools that align new datasets with them, facilitate comparison of brain data
      across experiments, laboratories, and from different imaging devices. The major
      methods are presented for the construction of probabilistic atlases, which store
      information on anatomic and functional variability in a population. Algorithms
      are reviewed that create composite brain maps and atlases based on multiple
      subjects. We show that group patterns of cortical organization, asymmetry, and
      disease-specific trends can be resolved that may not be apparent in individual
      brain maps. Finally, we describe the creation of four-dimensional (4D) maps that
      store information on the dynamics of brain change in development and disease.
      Digital atlases that correlate these maps show considerable promise in
      identifying general patterns of structural and functional variation in human
      populations, and how these features depend on demographic, genetic, cognitive,
      and clinical parameters.

PMID- 11323770
TI  - Magnetic resonance spectroscopy of the human brain.
AB  - Magnetic resonance (MR; synonymous with NMR = nuclear magnetic resonance) is a
      universal physical technique best known for non-invasive detection and anatomical
      mapping of water protons (H). MR-spectroscopy (MRS) records protons from tissue
      chemicals other than water, intrinsic phosphorus containing metabolites, sodium,
      potassium, carbon, nitrogen, and fluorine. MRS is therefore an imaging technique
      with the potential to record human and animal biochemistry in vivo. As a result
      of wide availability of MRI equipment in research laboratories and hospitals, MRS
      is a serious competitor with PET to define normal body composition and its
      perturbation by pharmacological and pathological events. This article describes
      practical aspects of in vivo MRS with particular emphasis on the brain, where
      novel metabolites have been described. A survey of these new aspects of
      neurochemistry emphasize their practical utility as neuronal and axonal markers,
      measures of energy status, membrane constituents, and osmolytes, as well as some
      xenobiotics, such as alcohol. The concept of multinuclear in vivo MRS is
      illustrated by diagnosis and therapeutic monitoring of several human brain
      disorders. Although these methods are currently most frequently encountered in
      human studies, as well as with transgenic and knockout mouse models, MRS adds a
      new dimension to anatomic and histopathologic descriptions.

PMID- 11323771
TI  - From anatomy to the target: contributions of magnetic resonance imaging to
      preclinical pharmaceutical research.
AB  - In recent years, in vivo magnetic resonance (MR) methods have become established
      tools in the drug discovery and development process. In this article, the role of
      MR imaging (MRI) in the preclinical evaluation of drugs in animal models of
      diseases is illustrated on the basis of selected examples. The individual
      sections are devoted to applications of anatomic, physiologic, and "molecular"
      imaging providing, respectively, structural-morphological, functional, and target
      specific information. The impact of these developments upon clinical drug
      evaluation is also briefly addressed. The main advantages of MRI are versatility,
      allowing a comprehensive characterization of a disease state and of the
      corresponding drug intervention; high spatial resolution; and noninvasiveness,
      enabling repeated measurements. Successful applications in drug discovery exploit
      one or several of these aspects. Additionally, MRI is contributing to strengthen
      the link between preclinical and clinical drug research.

PMID- 11323772
TI  - Three-dimensional microimaging (MRmicroI and microCT), finite element modeling,
      and rapid prototyping provide unique insights into bone architecture in
      osteoporosis.
AB  - With the proportion of elderly people increasing in many countries, osteoporosis
      has become a growing public health problem, with rising medical, social, and
      economic consequences. It is well recognized that a combination of low bone mass
      and the deterioration of the trabecular architecture underlies osteoporotic
      fractures. A comprehensive understanding of the relationships between bone mass,
      the three-dimensional (3D) architecture of bone and bone function is fundamental
      to the study of new and existing therapies for osteoporosis. Detailed analysis of
      3D trabecular architecture, using high-resolution digital imaging techniques such
      as magnetic resonance microimaging (MRmicroI), micro-computed tomography
      (microCT), and direct image analysis, has become feasible only recently. Rapid
      prototyping technology is used to replicate the complex trabecular architecture
      on a macroscopic scale for visual or biomechanical analysis. Further, a complete
      set of 3D image data provides a basis for finite element modeling (FEM) to
      predict mechanical properties. The goal of this paper is to describe how we can
      integrate three-dimensional microimaging and image analysis techniques for
      quantitation of trabecular bone architecture, FEM for virtual biomechanics, and
      rapid prototyping for enhanced visualization. The integration of these techniques
      provide us with an unique ability to investigate the role of bone architecture in
      osteoporotic fractures and to support the development of new therapies.

PMID- 11323773
TI  - Unfolding the human hippocampus with high resolution structural and functional
      MRI.
AB  - The hippocampus is a region of the brain that is crucial to memory function.
      Functional neuroimaging allows for the noninvasive investigation of the
      neurophysiology of human memory by observing changes in blood flow in the brain.
      We have developed a technique that employs high-resolution functional magnetic
      resonance imaging (fMRI) in combination with cortical unfolding to provide
      activation maps of the hippocampal region that surpass in anatomic and functional
      detail other methods of in vivo human brain mapping of the medial temporal lobe.
      We explain the principles behind this method and illustrate its application to a
      novelty-encoding paradigm.

PMID- 11323774
TI  - Contrast-enhanced color Doppler sonography of uveal melanomas.
AB  - PURPOSE: The purpose of our study was to evaluate the use of the galactose
      microbubble-based contrast agent Levovist in color Doppler sonography of uveal
      melanomas. We also evaluated the use of the resistance index and pulsatility
      index in differentiating tumor-associated vessels from normal vessels in patients
      with uveal melanomas. METHODS: In this prospective study, 40 patients with uveal
      melanoma were examined with color Doppler sonography before and after the
      administration of the contrast agent Levovist. The Doppler signals were recorded
      from both the tumor and the orbit and were evaluated quantitatively and
      qualitatively. RESULTS: Tumor-associated vessels were detected without contrast
      enhancement in 36 of 40 patients and with contrast enhancement in 38 of 40
      patients. The spectral characteristics of the Doppler signals did not change
      after the injection of Levovist. There were no differences-qualitative or
      quantitative-in Doppler signals between normal and tumor-associated vessels.
      CONCLUSIONS: The injection of Levovist slightly improved the detection of small
      vessels in uveal melanomas and the orbit but did not help to differentiate
      between normal vessels and tumoral vessels. The differentiation of a solid tumor
      from subretinal hemorrhage or effusion was improved.

PMID- 11323775
TI  - Correlation of color Doppler sonographic findings with pH measurements in
      gastroesophageal reflux in children.
AB  - PURPOSE: We conducted a prospective study of color Doppler sonography in children
      with suspected gastroesophageal reflux (GER). The purpose of this study was to
      compare the accuracy of color Doppler sonography with that of continuous 24-hour
      pH monitoring of the esophagus in diagnosing GER and to determine how to
      interpret the reflux episodes detected on color Doppler sonography in children at
      high risk for reflux. METHODS: Color Doppler sonography and 24-hour esophageal pH
      monitoring were performed in 54 children ranging in age from 2 months to 10 years
      (mean, 3 years). The stomach of each patient was filled for adequate gastric
      distention just before the color Doppler sonographic examination. We counted the
      number of reflux episodes over a period of 15 minutes. One day after the
      sonographic examination, the reflux was evaluated with esophageal pH monitoring,
      and the resultant reflux index (ReI) was obtained. The ReI was considered to be
      pathologic when it was equal to or greater than 11.99%. The number of refluxes on
      color Doppler sonography and the ReI were correlated for each patient. RESULTS:
      The 2 tests showed an 81.5% agreement in the detection of GER. When pH monitoring
      was taken as the reference test, color Doppler sonography had a high sensitivity
      (95.5%) for diagnosing GER but a very low specificity (11.0%), with a positive
      predictive value of 84.3% and a negative predictive value of 33.3%. There was no
      statistically significant correlation between the frequencies of GER detected on
      color Doppler sonography and the ReIs on pH monitoring (p = 0.1103). There was no
      correlation between the reflux grades on sonography and the ReI grades on pH
      monitoring (p = 0.422). CONCLUSIONS: Color Doppler sonography is highly sensitive
      and easier to use than pH monitoring. Although there are no definite criteria for
      evaluating the severity of GER on color Doppler imaging, this modality may be
      useful in screening children for GER.

PMID- 11323776
TI  - Urachal remnants in asymptomatic children: gray-scale and color Doppler
      sonographic findings.
AB  - PURPOSE: We undertook this study to evaluate the frequency of visualization and
      the sonographic appearances of urachal remnants (URs) in asymptomatic children.
      METHODS: One hundred eighty-two children without any urachus-related symptoms
      underwent sonography of the prevesical region and urinary bladder with high
      frequency transducers. RESULTS: A UR was visualized in 180 (99%) of the children.
      The URs had a mean length +/- standard deviation of 13 +/- 5 mm. Most of the URs
      were ovoid, and most demonstrated a moderate protrusion into the bladder cavity.
      The URs with a central echogenic area were larger than those without central
      echogenicity. In 36 (61%) of the 59 URs that were evaluated with color Doppler
      sonography, vascular signals were demonstrated within the lesion. The URs with
      internal vascular signals were significantly larger than those without internal
      vascular signals. CONCLUSIONS: The gray-scale and color Doppler sonographic
      characteristics of URs seem to be related to their size and their degree of
      involution rather than to the age of the child. We think that URs are present in
      almost all children. URs should be considered normal findings if they are
      asymptomatic and their length is not significantly greater than 22.5 mm, the 95th
      percentile in our study.

PMID- 11323777
TI  - Sonography of the normal scapholunate ligament and scapholunate joint space.
AB  - PURPOSE: The aims of this study were to assess the visibility of the normal
      scapholunate ligament on sonography and to establish the normal scapholunate
      joint space width in the neutral position and radial and ulnar deviation.
      METHODS: Two hundred normal wrists in 100 subjects (55 men and 45 women; mean
      age, 40 years; range, 19-83 years) were examined with high-resolution sonography
      (5-12-MHz linear-array transducer). The visibility and thickness of the
      scapholunate ligament were recorded. The width of the scapholunate joint space,
      or interval, was measured in the neutral position and radial and ulnar deviation.
      The width of the distal radius was recorded as a comparative standard for the
      patients' body habitus. RESULTS: The dorsal scapholunate ligament was completely
      (100%) visible in 95 wrists (48%), partially (> or = 50%) visible in 60 (30%),
      barely (< 50%) visible in 15 (8%), and not visible in 30 (15%). The volar
      scapholunate ligament was completely visible in 13 wrists (7%), partially visible
      in 17 (9%), barely visible in 15 (8%), and not visible in 151 (76%). The proximal
      component of the ligament was not visible in any subject. Measurement of the
      scapholunate interval was limited by the lack of identifiable anatomic marks for
      reference. The mean width of the dorsal scapholunate interval was 4.2 mm (range,
      2.3-6.3 mm) in the neutral position. The interval did not differ more than 2.5 mm
      between the left and right wrists. No predictable change in width on ulnar or
      radial deviation was evident. The mean scapholunate intervals and mean distal
      radial width were significantly wider in men than in women and on the right side
      than on the left side. CONCLUSIONS: The dorsal scapholunate ligament is
      completely or partially visible in 78% of normal wrists. Its detection following
      injury may help to exclude the possibility of scapholunate dissociation. There is
      a quite wide variation in scapholunate interval widths on sonography and an
      unpredictable response with stress testing. The absence of a visible scapholunate
      ligament on sonography does not indicate injury.

PMID- 11323778
TI  - Real-time sonography to estimate muscle thickness: comparison with MRI and CT.
AB  - PURPOSE: We investigated the feasibility of using real-time sonography to measure
      muscle thickness. Clinically, this technique would be used to measure the
      thickness of human muscles in which intramuscular microstimulators have been
      implanted to treat or prevent disuse atrophy. METHODS: Porcine muscles were
      implanted with microstimulators and imaged with sonography, MRI, and CT to assess
      image artifacts created by the microstimulators and to design protocols for image
      alignment between methods. Sonography and MRI were then used to image the deltoid
      and supraspinatus muscles of 6 healthy human subjects. RESULTS: Microstimulators
      could be imaged with all 3 methods, producing only small imaging artifacts.
      Muscle-thickness measurements agreed well between methods, particularly when
      external markers were used to precisely align the imaging planes. The correlation
      coefficients for sonographic and MRI measurements were 0.96 for the supraspinatus
      and 0.97 for the deltoid muscle. Repeated sonographic measurements had a low
      coefficient of variation: 2.3% for the supraspinatus and 3.1% for the deltoid
      muscle. CONCLUSIONS: Real-time sonography is a relatively simple and inexpensive
      method of accurately measuring muscle thickness as long as the operator adheres
      to a strict imaging protocol and avoids excessive pressure with the transducer.

PMID- 11323779
TI  - Renal infarct: contrast-enhanced power Doppler sonographic findings.
AB  - Power Doppler sonography (PDUS) is a promising technique for the diagnosis of
      renal infarcts. PDUS's efficacy may be enhanced by using sonographic contrast
      agents. We evaluated 3 cases of renal infarction using PDUS and the sonographic
      contrast agent Levovist. The findings were compared with those of other imaging
      modalities, such as scintigraphy, CT, and angiography. In case 1, PDUS showed a
      patent interlobar artery only in the lower part of the right kidney and no other
      perfusion of the right renal parenchyma. Contrast-enhanced PDUS showed patchy
      areas of preserved perfusion in the lower and middle-upper anterior portions of
      the kidney. In case 2, PDUS showed diffuse and patchy perfusion defects in the
      anterolateral portion of the right kidney. On contrast-enhanced PDUS, no signal
      enhancement was seen in these areas, but the perfusion defects were better
      delineated. In case 3, PDUS showed no perfusion in the upper pole of the kidney;
      the nonperfused area extended to the posterior upper portion of the kidney but
      could not be distinguished from normal tissue. After injection of the contrast
      agent, there was no enhancement of the posterior extension of the upper pole
      infarct, but Doppler signals from the surrounding normal parenchyma were
      enhanced, so the area was more clearly demarcated. The administration of the
      contrast agent facilitated the visualization of the infarcts in all 3 cases.

PMID- 11323780
TI  - Endosonographic appearances of Brunner's gland hamartomas.
AB  - Brunner's gland hamartoma is an uncommon intestinal tumor, most frequently
      located in the duodenal bulb. We report the endoscopic sonographic (EUS)
      appearances in 2 cases of Brunner's gland hamartoma. In 1 case, EUS revealed a
      heterogeneous hypoechoic pedunculated mass, 1.7 cm in diameter, arising from the
      mucosal and submucosal layers of the wall of the duodenal bulb. Multiple anechoic
      large and small cystic areas were demonstrated in the tumor. In the other case,
      EUS revealed a 1.4- x 0.9-cm pedunculated mass with an echogenicity higher than
      that of the muscular layer and lower than that of the mucosa, arising from the
      submucosal layer of the duodenal bulb wall. Multiple small anechoic areas were
      demonstrated in the tumor. We believe that both EUS patterns are typical for
      Brunner's gland hamartomas.

PMID- 11323781
TI  - Color Doppler sonographic diagnosis of dissecting aneurysm of the superior
      mesenteric artery.
AB  - We report a case of dissecting aneurysm of the superior mesenteric artery (SMA)
      diagnosed on gray-scale and color Doppler sonography and confirmed on
      angiography. Spontaneous dissection of the SMA is rare, and there are few
      reported cases of the color Doppler sonographic findings. Gray-scale sonography
      revealed an aneurysmal dilatation of the SMA 3-4 cm from the SMA's origin, with
      an echogenic linear membrane (an intimal flap) within the aneurysm. Color Doppler
      sonography showed color flow within the aneurysm and showed that the intimal flap
      separated the aneurysm into 2 lumina. Spectral analysis revealed anterograde flow
      in the anterior (ie, true) lumen and retrograde flow in the posterior (ie, false)
      lumen.

PMID- 11323782
TI  - Prenatal sonographic diagnosis of adrenal neuroblastoma.
AB  - Neuroblastoma is the most frequent extracranial solid tumor in childhood, but it
      is seldom diagnosed prenatally. We report a case of adrenal neuroblastoma
      identified at 39 weeks' menstrual age and successfully treated by postnatal
      surgery and chemotherapy. Sonography revealed a hyperechoic mass in the right
      upper quadrant of the fetal abdomen associated with hydramnios and
      hydronephrosis. Two days after delivery, the tumor was resected. No metastasis
      was identified. The infant received 6 cycles of chemotherapy, and at 2 years of
      age she was well, with no signs of recurrence.

PMID- 11323783
TI  - Sonographic diagnosis of Ascaris-induced cholecystitis and pancreatitis in a
      child.
AB  - We describe the sonographic diagnosis of Ascaris-induced acute cholecystitis and
      pancreatitis in a 2-year-old girl. Abdominal sonography revealed a grossly
      distended gallbladder with a thick (0.5-cm) wall. The common bile duct was
      dilated to 0.6 cm without sludge or calculi. The pancreas was hypoechoic, with an
      enlarged, 3.3-cm pancreatic head. Sonography showed dilatation of the small- and
      large-bowel loops, with multiple roundworms in duodenal and colonic loops.
      Sonography has an important role not only in the diagnosis of this uncommon
      condition but also in the documentation of its unusual etiologic agent.

PMID- 11323784
TI  - Cumulative exposure to styrene and visual functions.
AB  - BACKGROUND: Results from a 1990-1992 longitudinal study of several reinforced
      plastics plants showed that for those workers whose styrene exposure had
      decreased, color vision (CV) improved; while near visual contrast sensitivity
      (CS) was poorer. METHODS: In 1999, we retested these visual functions in 18
      workers with good visual acuity. A cumulative exposure index (CEI), corrected for
      respirator use, was calculated for each worker. RESULTS: Intra-individual
      comparison of mandelic acid (MA) showed a significant decrease over time
      (Friedman; P = 0.015), but current values were not related to CEI. For CV, no
      significant difference was observed between 1992 and 1999; present results were
      not related to MA or CEI. The CS profile decreased over time, with significant
      differences at 3 cpd (Friedman; P < 0.05). CS did not vary with MA levels, but
      was significantly depressed at the intermediate frequencies among those in the
      upper CEIH category (Kruskal-Wallis; P < 0.05). CONCLUSIONS: These findings
      suggest that CS loss increases with long-term cumulative exposure, reflecting
      chronic damage to the neuro-optic pathways.

PMID- 11323785
TI  - Agreement between clinical examination and quantitative tests of neurologic
      function among 384 subjects.
AB  - BACKGROUND: Quantitative neurological tests are often cheaper and easier than
      clinical examinations, and provide continuous data which may discriminate between
      exposed and nonexposed groups with more sensitivity than dichotomous
      (normal/abnormal) examination data. METHODS: We compare clinical examinations and
      analogous quantitative tests for arm tremor, postural sway, and vibrotactile
      sensitivity (finger and toe), for 384 subjects. RESULTS: The "abnormal" clinical
      outcomes studied were relatively common (range, 3-36%), and did not result in
      impairment of daily activity for affected subjects. All the quantitative tests
      were reasonably good predictors of the corresponding clinical outcome. The most
      predictive test was for toe vibrotactile sensitivity. The probability of an
      abnormal clinical result for those in the worst quartile for the toe test was
      0.63, compared with 0.36 for all subjects. CONCLUSIONS: Our results suggest that
      certain quantitative tests might be used in epidemiologic studies instead of a
      physical examination.

PMID- 11323786
TI  - Respiratory diseases caused by occupational exposure to 1,5-naphthalene
      diisocyanate (NDI): Results of workplace-related challenge tests and antibody
      analyses.
AB  - BACKGROUND: 1,5-naphthalene-diisocyanate (NDI) is an aromatic diisocyanate with a
      very low vapor pressure which is mainly used in the automotive industry. METHODS:
      In the present study we described five cases with workplace-related asthma and
      one case with extrinsic allergic alveolitis associated with pulmonary hemorrhage
      after NDI exposure. RESULTS: Corresponding to case histories, extrinsic
      alveolitis on asthmatic reactions in three subjects and a rhinitis reaction in
      one patient could be reproduced by inhalative challenge tests to NDI at a
      concentration of 10 ppb. Preliminary IgE and IgG antibody analyses in patients'
      sera did not produce significantly positive results. CONCLUSIONS: According to
      the outcome of our tests and in comparison with several other studies, we
      conclude that NDI should be classified as potent airway-sensitizing substance.
      Improved workplace conditions and decrease in threshold limit values should
      therefore be recommended.

PMID- 11323787
TI  - Mortality among unionized construction plasterers and cement masons.
AB  - BACKGROUND: Plasterers perform a variety of duties including interior and
      exterior plastering of drywall, cement, stucco, and stone imitation; the
      preparation, installation, and repair of all interior and exterior insulation
      systems; and the fireproofing of steel beams and columns. Some of the current
      potential toxic exposures among plasterers include plaster of Paris, silica,
      fiberglass, talc, and 1,1,1-trichloroethylene; asbestos had been used by the
      plasterers in the past. Cement masons, on the other hand, are involved in
      concrete construction of buildings, bridges, curbs and gutters, sidewalks,
      highways, streets and roads, floors and pavements and the finishing of same, when
      necessary, by sandblasting or any other method. Exposures include cement dust,
      silica, asphalt, and various solvents. METHODS: Proportionate mortality ratios
      (PMRs) and proportionate cancer mortality ratios (PCMRs) were calculated for 99
      causes of death among 12,873 members of the Operative Plasterers' and Cement
      Masons' International Association who died between 1972 and 1996 using United
      States age-, race-, and calender-specific death rates. Statistical significance
      (P value) of results was based upon the Poisson distribution. RESULTS: Among
      plasterers, statistically significant elevated mortality was observed for
      asbestosis, where the PMR reached 1,657 (P < 0.01) with eleven observed deaths
      and less than one death expected, for lung cancer (PCMR = 124, P < 0.01), and for
      benign neoplasms (PMR = 210, P < 0.05). Among cement masons, statistically
      significant elevated mortality was observed for cancer of the stomach (PCMR =
      133, P < 0.01), benign neoplasms (PMR = 132, P < 0.01), and poisonings (PMR =
      159, P < 0.05). Except for poisonings, which were not thought to be
      occupationally related, all of the statistically significant results occurred
      among those members who entered the union prior to 1950. However, the risk for
      lung cancer among plasterers was still elevated among those entering the union
      after 1970 as was the risk for stomach cancer among cement masons who entered the
      union after 1950. CONCLUSIONS: The present study suggests that plasterers and
      cement masons still have elevated risks for certain diseases, especially lung and
      stomach cancer. Therefore, union members currently living should be screened for
      asbestos-related diseases and educated about the future risks for these diseases.

PMID- 11323788
TI  - Risk of hand-arm vibration syndrome according to occupation and sources of
      exposure to hand-transmitted vibration: A national survey.
AB  - BACKGROUND: Although some occupational sources of hand-transmitted vibration
      (HTV) have been extensively investigated, the risks associated with others are
      poorly characterized. METHODS: A questionnaire was mailed to a community sample
      of 12,240 men aged 16- 64 years and 906 men from the armed forces. Questions
      covered current occupation, sources of HTV, numbness or tingling in the fingers
      in the past week, and finger blanching. In the 5,364 respondents who had been at
      work in the past week, associations between symptoms and exposures were examined
      by logistic regression, with odds ratios converted into prevalence ratios (PRs).
      RESULTS: Altogether, 513 men (10%) reported cold-induced finger blanching and 769
      (14%) sensory symptoms in the fingers. The risk of blanching was increased in
      builders (PR 2.4, 95% CI 1.0-5.2), carpenters and joiners (PR 1.9, 95% CI 1.0
      3.4), motor mechanics (PR 2.3, 95% CI 1.1-4.6), and laborers (PR 2.8, 95% CI 1.3
      6.0); while the risk of sensory symptoms was elevated in laborers (PR 4.0, 95% CI
      2.3-6.6) and plant operatives (PR 3.5, 95% CI 1.9-5.9). Use of hand-guided
      mowers, concrete breakers, chain saws, and jig saws was significantly associated
      with symptoms. CONCLUSIONS: Little attention has been paid to the risks of
      vibration injury in construction workers, woodworkers, motor mechanics, and
      laborers, or to the risks from mowers, jig saws and several other common
      vibratory tools. These should be a focus for further investigation and preventive
      measures.

PMID- 11323789
TI  - Measuring psychosocial job strain with the job content questionnaire using
      experienced job evaluators.
AB  - BACKGROUND: A union/management system of job evaluation has been in place in the
      British Columbia (BC) sawmill industry since the late 1960s. This system uses an
      instrument, very similar to the job content questionnaire (JCQ) to evaluate
      psychosocial work conditions for sawmill jobs. METHODS: Four experienced
      evaluators, one from the union and three from industry, independently estimated
      psychosocial work conditions for 54 current job titles in a "typical" coastal
      sawmill using a shortened, 18-question version of the JCQ questionnaire. RESULTS:
      Inter-rater reliability was acceptable for control but not for co-worker social
      support, physical demand, or psychological demand. Reliability was least for
      psychological demand. CONCLUSIONS: Experienced job evaluators in the sawmill
      industry were able to reliably estimate only the control dimension of the JCQ.
      The observed lowest reliability for psychological job demand may be due to the
      imprecise construct definition in the domain of the JCQ instrument.

PMID- 11323790
TI  - Control of chemical risks during the treatment of soil contaminated with
      chlorophenol, creosote and copper-chrome-arsenic-wood preservatives.
AB  - BACKGROUND: Exposure to chemicals in polluted soil was studied during the
      remediation of four polluted sites. They are sawmill areas contaminated with
      chlorophenols and polychlorinated dibenzo-p-dioxins and furanes (PCDD/F), wood
      impregnating plants contaminated with polycyclic aromatic hydrocarbons (PAH) from
      creosote oil, old gas works area contaminated with PAH, and a wood impregnation
      plant contaminated with copper-chromium-arsenic (CCA) preservative. METHODS: The
      exposure levels were determined by both air and biological monitoring. RESULTS:
      Air monitoring showed that the exposure levels were generally well below the
      current occupational exposure limits. The calculations indicated, however, that
      the lowest acceptable daily intake value recommended for PCDD/F by the U.S.
      Environmental Protection Agency was exceeded. Chlorophenol exposure was generally
      low. Exposure to volatile PAH was 0.038-0.884 mg/m(3) and that to particulate PAH
      was 0.004-0.183 mg/m(3). The biomonitoring results (urinary 1-pyrenol) suggested
      that some exposure occurs, probably through the contamination of hands or skin
      absorption. At the sites contaminated with CCA salts, no exposure limits were
      exceeded. CONCLUSIONS: The results generally suggest that the exposure of cleanup
      workers is generally below the current occupational exposure limits but that
      short-term high exposure cannot be excluded. There was also some indication of
      poor skin protection, which should be improved when soil contaminated with PAH
      and creosote oil is handled.

PMID- 11323791
TI  - Respiratory symptoms in Swiss farmers: an epidemiological study of risk factors.
AB  - BACKGROUND: The study was undertaken to assess the prevalence and risk factors of
      self-reported asthma, symptoms of chronic bronchitis, hay fever, and work-related
      respiratory symptoms in Swiss farmers as well as to compare the prevalence rates
      of respiratory symptoms with the Swiss population (SAPALDIA-Study). METHODS: An
      epidemiological study was performed with a representative sample of 1,542 Swiss
      farmers using a self-administered questionnaire. To investigate the effect of the
      type of farming on reported symptoms, the farmers were subdivided into seven
      groups according to the time farmers spent in different animal confinement
      buildings. A multivariate analysis was performed by the methods of binary and
      multivariate logistic regression adjusted for age and smoking habits. RESULTS: In
      farmers the prevalence rate was 16.0% for chronic bronchitis, 15.4% for asthma
      symptoms, and 42.0% for reporting at least one work-related symptom. Using
      logistic regression analysis, it was established that poultry farming and
      pig/cattle farming was a risk factor for reporting nasal irritation at work [OR
      5.33, (1.57-18.0), OR 3.37 (1.04-10.87)]. Poultry farmers experienced the highest
      symptom rates. In crop farmers, the prevalence for chronic bronchitis was
      increased [OR 2.32 (1.03-5.23)]. Over 4 hr spent per day in animal confinement
      buildings more than doubled the risk for reporting chronic bronchitis [OR 2.61
      (1.01-6.76)] and phlegm [OR 2.3 (0.99-5.4)] independent of the type of farming.
      The comparison of Swiss farmers with the Swiss population showed a twofold
      elevated risk of reporting chronic bronchitis [OR 1.89 (1.32-2.95)] and a 4.5
      fold elevated risk for bringing up phlegm regularly [OR 4.5 (3.25-6.69)] in
      farmers. In contrast, the risk of farmers to report nasal allergies was less than
      half as high [OR 0.40 (0.29-0.56)] as that of the general population.
      CONCLUSIONS: This study shows that agricultural work in Switzerland is associated
      with an elevated risk for reporting symptoms of chronic bronchitis and chronic
      phlegm compared with the general Swiss population. These main results most likely
      indicate occupational disorders as the exposure-response relationship (hours
      spent in animal confinements) was particularly obvious for these symptoms.

PMID- 11323792
TI  - Respiratory symptoms, lung function and cell surface markers in a group of hemp
      fiber processors.
AB  - BACKGROUND: Hemp dust exposure is associated with byssinosis and accelerated lung
      loss in longitudinal studies. The immunological changes associated with hemp dust
      exposure are less well understood. METHODS: We studied a small group of current
      male hemp processors with a mean age of 43 years. Questionnaire data, lung
      function, serial FEV(1) and blood were collected from all workers. RESULTS: In
      total, seven workers (64%) complained of at least one respiratory symptom (one
      with byssinosis). The mean percentage predicted FEV(1) was 91.5, FVC 97.7, PEF
      92.1, and FEF(25-75) 79.5. Serial FEV(1) measurements in the two workers with
      work-related respiratory symptoms revealed a mean change in FEV(1) on the first
      working day of -12.9%. This contrasted with +6.25% on the last working day.
      Respective values for the two workers without work-related symptoms were -1.4 and
      +3.2%. CONCLUSIONS: Lung function changes and abnormalities in a profile of cell
      surface activation markers and antibodies were noted to relate to the presence of
      work-related respiratory symptoms, not seen in the control group.

PMID- 11323793
TI  - Use of MMT in Canadian gasoline: health and environment issues.
AB  - BACKGROUND: Methylcyclopentadienyl manganese tricarbonyl (MMT) is an organic
      derivative of manganese (Mn) used in Canadian gasoline since 1976 as an antiknock
      agent and to improve octane rating. Combustion products of MMT are mainly a
      mixture of Mn phosphate and Mn sulfate. In 1997, the Canadian federal government
      adopted a law (C-29) which banned both the interprovincial trade and the
      importation for commercial purposes of manganese-based substances, including MMT.
      However, the government reworded this law in July 1998 so that manganese-based
      fuel additives were not included in the restrictions. MMT is now approved for use
      in Argentina, Australia, Bulgaria, the United States, France, Russia, and
      conditionally in New Zealand. Nevertheless, these countries are not using MMT
      intensively and they are waiting for strong evidence of the absence of effects on
      human health. Even after several years of use of MMT in Canada, many
      uncertainties remain. METHODS: Different methods were used in order to assess (1)
      environmental contamination and human exposure to the parental form of MMT, (2)
      nitrogen oxides (NO(x)) and carbon monoxide (CO) emissions associated with the
      use of MMT, and (3) qualitative and quantitative assessments of Mn emissions to
      the environment. RESULTS: The results provide timely information with regard to
      the impact of MMT on environmental/ecosystem Mn contamination in abiotic and
      biotic systems as well as on human exposure. Moreover, results raise major
      concerns with regard to public health effects related to exposure to Mn.
      CONCLUSIONS: Obviously, there is still an important lack of adequate
      toxicological information and further studies are needed to provide successful
      implementation of evidence-based risk assessment approaches.

PMID- 11323794
TI  - MMT, deja vu and national security.

PMID- 11323795
TI  - Re: mortality among workers in the geothermal power plants at Larderello, Italy.
      Am. J. Ind. Med. 35:536-539, 2000.

PMID- 11323797
TI  - Online motion correction for diffusion-weighted imaging using navigator echoes:
      Application to RARE imaging without sensitivity loss.
AB  - This article describes the first application of true online motion correction to
      diffusion-weighted RARE imaging. Two orthogonal navigator echoes were acquired
      and zeroth and first-order phase corrections applied in less than 8 ms between a
      diffusion-weighted magnetization preparation and data acquisition using the RARE
      sequence. The zeroth-order phase correction was realized by pulsing the system's
      B(0)-coil: the first-order error corrected with appropriate magnetic field
      gradient pulses. Online correction ensured that no irreversible signal loss could
      occur in the imaging experiment. Diffusion-weighted images of the brain were
      obtained from healthy volunteers. EGG-triggered acquisition was applied at 400 ms
      after the R-wave. Data were acquired on a matrix of 256 x 256 with a RARE factor
      of 16 and a b-value of 804 smm(-2). The images obtained with online motion
      correction showed a remarkably high image quality, while those acquired without
      motion correction were severely degraded by artifacts.

PMID- 11323798
TI  - Highly diffusion-sensitized MRI of brain: dissociation of gray and white matter.
AB  - The brains of six healthy volunteers were scanned with a full tensor diffusion
      MRI technique to study the effect of a high b value on diffusion-weighted images
      (DWIs). The b values ranged from 500 to 5000 s/mm(2). Isotropic DWIs, trace
      apparent diffusion coefficient (ADC) maps, and fractional anisotropy (FA) maps
      were created for each b value. As the b value increased, ADC decreased in both
      the gray and white matter. Furthermore, ADC of the white matter became lower than
      that of the gray matter, and, as a result, the white matter became brighter than
      the gray matter in the isotropic DWIs. Quantitative analysis showed that these
      changes were due to nonmonoexponential diffusion signal decay of the brain
      tissue, which was more prominent in white matter than in gray matter. There was
      no significant change in relation to the b value in the FA maps. High b value
      appears to have a dissociating effect on gray and white matter in DWIs.

PMID- 11323799
TI  - Single-shot diffusion trace (1)H NMR spectroscopy.
AB  - Ignoring diffusion anisotropy can severely hamper the quantitative determination
      of water and metabolite diffusion in complex tissues. The measurement of the
      trace of the diffusion tensor provides unambiguous and rotationally invariant ADC
      values, but usually requires three separate experiments. A single-shot technique
      developed earlier, originally designed for diffusion trace MR imaging (Mori and
      van Zijl, Magn Reson Med 1995;33:41-52), was improved and adapted for diffusion
      trace MR spectroscopy. A double spin-echo pulse sequence was incorporated with
      four pairs of bipolar gradients with specific predetermined relative signs in
      each of the three orthogonal directions. The combination of gradient directions
      leads to cancellation of all off-diagonal tensor elements while constructively
      adding the diagonal elements. Furthermore, the pulse scheme provides complete
      compensation for cross-terms between static magnetic field gradients and the
      applied diffusion gradients, while simultaneously avoiding cross-terms with
      localization gradients. The sequence was tested at 4.7 T in vivo on rat brain for
      MRI and on rat skeletal muscle and brain for MRS. It is shown that the average
      ADC as determined from the measurement of the ADCs in the three orthogonal
      directions is in close agreement with the ADC obtained along the trace of the
      diffusion tensor in a single acquisition, for both water and metabolite
      diffusion. The large differences in water and metabolite diffusion coefficients
      as measured in the individual orthogonal directions illustrate the need for
      diffusion trace measurements when accurate and rotationally invariant diffusion
      quantitation is required. The pulse scheme presented here may be applied for such
      purposes in MRS and MRI studies.

PMID- 11323800
TI  - Real-time measurements of cellular oxygen consumption, pH, and energy metabolism
      using nuclear magnetic resonance spectroscopy.
AB  - Changes in molecular expression or apoptotic behavior, induced by malignant
      transformation or anticancer treatment, are frequently reflected in cellular
      metabolism and oxygen consumption. A technique to monitor oxygen consumption,
      cell physiology, and metabolism noninvasively would provide a better
      understanding of interactions between molecular changes and metabolism in
      malignant transformation and following cancer treatment. Such a system was
      developed in this study by adapting multinuclear MRI and spectroscopic techniques
      to an isolated cell perfusion system. The system was evaluated by studying the
      effects of two agents, carbonyl cyanide m-chlorophenylhydrazone (CCCP) which is
      an uncoupler of oxidative phosphorylation, and antimycin, an inhibitor of
      oxidative phosphorylation, on the oxygen consumption and metabolism of MCF-7 and
      MatLyLu cancer cell lines.

PMID- 11323801
TI  - Detection of myocardial viability based on measurement of sodium content: A
      (23)Na-NMR study.
AB  - MRI of total sodium (Na) content may allow assessment of myocardial viability,
      but information on Na content in normal myocardium, necrotic/scar tissue, and
      stunned or hibernating myocardium is lacking. Thus, the aims of the study were
      to: 1) quantify the temporal changes in myocardial Na content post-myocardial
      infarction (MI) in a rat model (Protocol 1); 2) compare Na in normally perfused,
      hibernating, and stunned canine myocardium (Protocol 2); and 3) determine
      whether, in buffer-perfused rat hearts, infarct scar can be differentiated from
      intact myocardium by (23)Na-MRI (Protocol 3). In Protocol 1, rats were subjected
      to LAD ligation. Infarct/scar tissue was excised at control and 1, 3, 7, 28, 56,
      and 128 days post-MI (N = 6-8 each), Na content was determined by (23)Na-NMR
      spectroscopy (MRS) and ion chromatography. Na content was persistently increased
      at all time points post-MI averaging 306*-160*% of control values (*P < 0.0083
      vs. control). In Protocol 2, (23)Na-MRS of control (baseline), stunned and
      hibernating samples revealed no difference in Na. In Protocol 3, (23)Na-MRI
      revealed a mean increase in signal intensity, to 142 +/- 6% of control values, in
      scar tissue. A threshold of 2 standard deviations of the image intensity allowed
      determination of infarct size, correlating with histologically determined infarct
      size (r = 0.91, P < 0.0001).

PMID- 11323802
TI  - Single-voxel proton MRS of the human brain at 1.5T and 3.0T.
AB  - Single-voxel proton spectra of the human brain were recorded in five subjects at
      both 1.5T and 3.0T using the STEAM pulse sequence. Data acquisition parameters
      were closely matched between the two field strengths. Spectra were recorded in
      the white matter of the centrum semiovale and in phantoms. Spectra were compared
      in terms of resolution and signal-to-noise ratio (SNR), and transverse relaxation
      times (T(2)) were estimated at both field strengths. Spectra at 3T demonstrated a
      20% improvement in sensitivity compared to 1.5T at short echo times (TE = 20
      msec), which was lower than the theoretical 100% improvement. Spectra at long
      echo times (TE = 272 msec) exhibited similar SNR at both field strengths. T(2)
      relaxation times were almost twofold shorter at the higher field strength.
      Spectra in phantoms demonstrated significantly improved resolution at 3T compared
      to 1.5T, but resolution improvements in in vivo spectra were almost completely
      offset by increased linewidths at higher field.

PMID- 11323803
TI  - Analysis of partial volume effects in diffusion-tensor MRI.
AB  - The diffusion tensor is currently the accepted model of diffusion in biological
      tissues. The measured diffusion behavior may be more complex when two or more
      distinct tissues with different diffusion tensors occupy the same voxel. In this
      study, a partial volume model of MRI signal behavior for two diffusion-tensor
      compartments is presented. Simulations using this model demonstrate that the
      conventional single diffusion tensor model could lead to highly variable and
      inaccurate measurements of diffusion behavior. The differences between the single
      and two-tensor models depend on the orientations, fractions, and exchange between
      the two diffusion tensor compartments, as well as the diffusion-tensor encoding
      technique and diffusion-weighting that is used in the measurements. The current
      single compartment model's inaccuracies could cause diffusion-based
      characterization of cerebral ischemia and white matter connectivity to be
      incorrect. A diffusion-tensor MRI imaging experiment on a normal human brain
      revealed significant partial volume effects between oblique white matter regions
      when using very large voxels and large diffusion-weighting (b approximately 2.69
      x 10(3) sec/mm(2)). However, the apparent partial volume effects in white matter
      decreased significantly when smaller voxel dimensions were used. For diffusion
      tensor studies obtained using typical diffusion-weighting values (b approximately
      1 x 10(3) sec/mm(2)) partial volume effects are much more difficult to detect and
      resolve. More accurate measurements of multiple diffusion compartments may lead
      to improved confidence in diffusion measurements for clinical applications.

PMID- 11323804
TI  - High-resolution (1)H NMR and magic angle spinning NMR spectroscopic investigation
      of the biochemical effects of 2-bromoethanamine in intact renal and hepatic
      tissue.
AB  - The metabolic consequences of xenobiotic-induced toxicity were investigated using
      high-resolution magic angle spinning (MAS) NMR spectroscopy of intact tissue.
      Renal papillary necrosis (RPN) was induced in Sprague-Dawley rats (n = 12) via a
      single i.p. dose of 250 mg/kg 2-bromoethanamine (BEA) hydrobromide. At 2, 4, 6,
      and 24 h after treatment with BEA, three animals were killed and tissue samples
      were obtained from liver, renal cortex, and renal medulla. Tissue samples were
      also removed at 2 and 24 h from matched controls (n = 6). (1)H MAS NMR
      spectroscopic techniques were used to analyze samples of intact tissue (
      approximately 10 mg). Decreased levels of nonperturbing renal osmolytes
      (glycerophosphocholine, betaine, and myo-inositol) were observed in the renal
      papilla of BEA-treated animals at 6 and 24 h postdose (p.d.), concomitant with a
      relative increase in the tissue concentration of creatine. Increased levels of
      glutaric acid were found in all tissues studied in BEA-treated animals at 4 and 6
      h p.d., indicating the inhibition of mitochondrial fatty acyl CoA dehydrogenases
      and mitochondrial dysfunction. Increased levels of trimethylamine-N-oxide
      occurred in the renal cortex at 6 h p.d. Changes in the metabolite profile of
      liver included an increase in the relative concentrations of triglycerides,
      lysine, and leucine. The novel application of (1)H MAS NMR to the biochemical
      analysis of intact tissues following a toxic insult highlights the potential of
      this technique as a toxicological probe in providing a direct link between
      urinary biomarkers of toxicity and histopathological evaluation of toxicological
      lesions.

PMID- 11323805
TI  - Relative changes of cerebral arterial and venous blood volumes during increased
      cerebral blood flow: implications for BOLD fMRI.
AB  - Measurement of cerebral arterial and venous blood volumes during increased
      cerebral blood flow can provide important information regarding hemodynamic
      regulation under normal, pathological, and neuronally active conditions. In
      particular, the change in venous blood volume induced by neural activity is one
      critical component of the blood oxygenation level-dependent (BOLD) signal because
      BOLD contrast is dependent only on venous blood, not arterial blood. Thus,
      relative venous and arterial blood volume (rCBV) and cerebral blood flow (rCBF)
      in alpha-chlorolase-anesthetized rats under hypercapnia were measured by novel
      diffusion-weighted (19)F NMR following an i.v. administration of intravascular
      tracer, perfluorocarbons, and continuous arterial spin labeling methods,
      respectively. The relationship between rCBF and total rCBV during hypercapnia was
      rCBV(total) = rCBF(0.40), which is consistent with previous PET measurement in
      monkeys. This relationship can be linearized in a CBF range of 50-130 ml/100
      g/min as DeltarCBV(total)/ DeltarCBF = 0.31 where DeltarCBV and DeltarCBF
      represent rCBV and rCBF changes. The average arterial volume fraction was 0.25 at
      a basal condition with CBF of approximately 60 ml/100 g/min and increased up to
      0.4 during hypercapnia. The change in venous rCBV was 2-fold smaller than that of
      total rCBV (DeltarCBV(vein)/DeltarCBF = 0.15), while the arterial rCBV change was
      2.5 times larger than that of total rCBV (DeltarCBV(artery)/DeltarCBF = 0.79).
      These NMR results were confirmed by vessel diameter measurements with in vivo
      videomicroscopy. The absolute venous blood volume change contributes up to 36% of
      the total blood volume change during hypercapnia. Our findings provide a
      quantitative physiological model of BOLD contrast.

PMID- 11323806
TI  - Extracellular apparent diffusion in rat brain.
AB  - The apparent diffusion coefficients (ADCs) of a series of markers concentrated in
      the extracellular space of normal rat brain were measured to evaluate, by
      inference, the ADC of water in the extracellular space. The markers (mannitol,
      phenylphosphonate, and polyethylene glycols) are defined as "compartment
      selective" because tissue culture experiments demonstrate some leakage into the
      intracellular space, making them less "compartment specific" than commonly
      believed. These primarily extracellular markers have ADCs similar to those of
      intracellular metabolites of comparable hydrodynamic radius, suggesting that
      water ADC values in the intra- and extracellular spaces are similar. If this is
      the case, then it is unlikely that a net shift of water from the extra- to the
      intracellular space contributes significantly to the reduction in water ADC
      detected following brain injury. Rather, this reduction is more likely due
      primarily to a reduction of the ADC of intracellular water associated with
      injury.

PMID- 11323807
TI  - Separation and quantification of perfusion and BOLD effects by simultaneous
      acquisition of functional I(0)- and T2(*)-parameter maps.
AB  - The nature of the coupling between neuronal activity and the hemodynamic response
      is the subject of intensive research. As a means to simultaneously measure
      parametric changes of T2(*), initial intensity (I(0)) and perfusion with high
      temporal resolution, a multi-image EPI technique with slice-selective inversion
      recovery (ssIR) for arterial spin labeling was developed and implemented.
      Comparative measurements with and without the preceding slice-selective inversion
      pulse were performed. I(0) and R2(*) changes induced by primary visual
      stimulation were separated. For ssIR-multi-image EPI the average change of I(0)
      over all 12 subjects was 3.4%, corresponding to a perfusion change of 40
      ml/min/100 g, whereas only minor I(0) changes were observed without inversion. On
      average, the R2(*) of the activated pixels changed by -0.62 sec(-1) without
      inversion, while a significantly reduced average R2(*) change of -0.46 sec(-1)
      was calculated for ssIR-multi-image EPI due to a decreased BOLD effect
      contribution of the intravascular compartment.

PMID- 11323808
TI  - Accurate phosphorus metabolite images of the human heart by 3D acquisition
      weighted CSI.
AB  - Fourier imaging modalities suffer from significant signal contamination between
      adjacent voxels, especially when the spatial resolution is comparable to the size
      of the anatomical structures. This contamination can be positive or negative,
      depending on the spatial response function and the geometry of the object. Such a
      situation arises in human cardiac (31)P chemical shift imaging (CSI). Acquisition
      weighted CSI reduces this contamination substantially, which is demonstrated by
      comparing conventional CSI to Hanning-weighted 3D (31)P-CSI experiments in 13
      healthy volunteers at 2 T. The nominal spatial resolution and the total number of
      scans were identical for both experiments. The improved spatial response function
      of the acquisition-weighted experiment led to a significantly (P < 0.0001) higher
      myocardial PCr/ATP ratio (2.05 +/- 0.31, mean +/- SD, N = 33, corrected for
      saturation and blood contribution) compared to the conventional CSI experiment
      (1.60 +/- 0.46). This is explained by the absence of negative contamination from
      skeletal muscle, which also resulted in an increase of the observed SNR (from 5.4
      +/- 1.4 to 7.2 +/- 1.4 for ATP). With acquisition-weighted CSI, metabolic images
      with a nominal resolution of 16 ml could be obtained in a measurement time of 30
      min. After correction for the inhomogeneous B(1) field of the surface coil, these
      images show uniform ATP distribution in the entire myocardium, including the
      posterior wall.

PMID- 11323809
TI  - Three-dimensional subzone-based reconstruction algorithm for MR elastography.
AB  - Accurate characterization of harmonic tissue motion for realistic tissue
      geometries and property distributions requires knowledge of the full three
      dimensional displacement field because of the asymmetric nature of both the
      boundaries of the tissue domain and the location of internal mechanical
      heterogeneities. The implications of this for magnetic resonance elastography
      (MRE) are twofold. First, for MRE methods which require the measurement of a
      harmonic displacement field within the tissue region of interest, the presence of
      3D motion effects reduces or eliminates the possibility that simpler, lower
      dimensional motion field images will capture the true dynamics of the entire
      stimulated tissue. Second, MRE techniques that exploit model-based elastic
      property reconstruction methods will not be able to accurately match the observed
      displacements unless they are capable of accounting for 3D motion effects. These
      two factors are of key importance for MRE techniques based on linear elasticity
      models to reconstruct mechanical tissue property distributions in biological
      samples. This article demonstrates that 3D motion effects are present even in
      regular, symmetric phantom geometries and presents the development of a 3D
      reconstruction algorithm capable of discerning elastic property distributions in
      the presence of such effects. The algorithm allows for the accurate determination
      of tissue mechanical properties at resolutions equal to that of the MR
      displacement image in complex, asymmetric biological tissue geometries.
      Simulation studies in a realistic 3D breast geometry indicate that the process
      can accurately detect 1-cm diameter hard inclusions with 2.5x elasticity contrast
      to the surrounding tissue.

PMID- 11323810
TI  - Accurate multislice gradient echo T(1) measurement in the presence of non-ideal
      RF pulse shape and RF field nonuniformity.
AB  - A methodology is presented for estimating T(1) using a two-point technique with a
      standard multislice gradient echo sequence. The method explicitly corrects for
      the shape of the RF pulse and for spatial variations in transmitted RF field
      intensity. Including these factors in the calculation of T(1) gives a substantial
      improvement in accuracy and precision of two-point gradient echo T(1)
      measurements in the presence of RF nonuniformity and non-ideal pulse profiles.
      The mean accuracy of the technique was found to be 1.4%. The mean precision was
      found to be 3.0%. The mean variation along the axis of a head coil was found to
      be 2.3%.

PMID- 11323811
TI  - Adaptive sensitivity encoding incorporating temporal filtering (TSENSE).
AB  - A number of different methods have been demonstrated which increase the speed of
      MR acquisition by decreasing the number of sequential phase encodes. The UNFOLD
      technique is based on time interleaving of k-space lines in sequential images and
      exploits the property that the outer portion of the field-of-view is relatively
      static. The differences in spatial sensitivity of multiple receiver coils may be
      exploited using SENSE or SMASH techniques to eliminate the aliased component that
      results from undersampling k-space. In this article, an adaptive method of
      sensitivity encoding is presented which incorporates both spatial and temporal
      filtering. Temporal filtering and spatial encoding may be combined by acquiring
      phase encodes in an interleaved manner. In this way the aliased components are
      alternating phase. The SENSE formulation is not altered by the phase of the alias
      artifact; however, for imperfect estimates of coil sensitivities the residual
      artifact will have alternating phase using this approach. This is the essence of
      combining temporal filtering (UNFOLD) with spatial sensitivity encoding (SENSE).
      Any residual artifact will be temporally frequency-shifted to the band edge and
      thus may be further suppressed by temporal low-pass filtering. By combining both
      temporal and spatial filtering a high degree of alias artifact rejection may be
      achieved with less stringent requirements on accuracy of coil sensitivity
      estimates and temporal low-pass filter selectivity than would be required using
      each method individually. Experimental results that demonstrate the adaptive
      spatiotemporal filtering method (adaptive TSENSE) with acceleration factor R = 2,
      for real-time nonbreath-held cardiac MR imaging during exercise induced stress
      are presented.

PMID- 11323812
TI  - Simultaneous noninvasive measurement of CBF and CBV using double-echo FAIR
      (DEFAIR).
AB  - A new method for measuring cerebral blood flow (CBF) and cerebral blood volume
      (CBV) noninvasively using MRI is presented. The approach is based on the
      technique of arterial spin labelling (ASL), in which CBF-based contrast is
      generated by controlled modulation of the longitudinal magnetization of the
      blood. The proposed method also uses differences in T(2) between tissue and blood
      to differentiate the two compartments and allow assessment of the relative size
      of each. Two successive EPI images are acquired following spin preparation using
      either a slice-selective or global inversion pulse, and the technique is
      therefore referred to as double-echo FAIR (DEFAIR). DEFAIR is demonstrated in the
      normal gerbil brain and during hypothermia, where reductions of both CBF and CBV
      are known to occur. It is also shown theoretically that this method can be
      extended to include a measurement of oxygen extraction fraction. The main
      drawbacks of the technique are the long acquisition time and relatively low
      sensitivity to hemodynamic changes compared to conventional qualitative T2(*)
      weighted BOLD contrast, which may limit its applicability and practical use in
      monitoring functional cerebral activation. However, the technique can be used
      repetitively in longer-term time course studies due to its noninvasive and
      quantitative nature.

PMID- 11323813
TI  - Examining a canine model of stunned myocardium with Gd-DTPA-enhanced MRI.
AB  - It has previously been shown that the distribution volume of Gd-DTPA (lambda) in
      infarcted, canine myocardium is higher than that of normal tissue. The purpose of
      this study was to determine whether stunned myocardium exhibits increased lambda.
      Stunning was produced in beagles by means of 30 min LAD occlusion followed by 3
      weeks (n = 4) reperfusion. Gd-DTPA was infused at each imaging session and lambda
      determined in vivo using a saturation recovery turboFLASH sequence; cine imaging
      was used to assess ventricular wall thickening (%WT). (201)Tl uptake was used as
      an independent assessment of viability. %WT data confirmed that the brief insult
      caused prolonged, yet reversible, regional contractile dysfunction in each
      animal. %WT was not significantly different from baseline values by 3 weeks post
      reflow. Normal (201)Tl uptake confirmed the absence of infarction. The lambda of
      stunned tissue (lambda = 0.381 +/- 0.030 ml/g) was not elevated above that of
      normal tissue (lambda = 0.398 +/- 0.027 ml/g, P = NS), at any time point studied,
      in vivo. These data suggest that an increase in lambda is a specific indicator of
      irreversible damage.

PMID- 11323814
TI  - Estimation of relative cardiovascular pressures using time-resolved three
      dimensional phase contrast MRI.
AB  - Accurate, easy-to-use, noninvasive cardiovascular pressure registration would be
      an important addition to the diagnostic armamentarium for assessment of cardiac
      function. A novel noninvasive and three-dimensional (3D) technique for estimation
      of relative cardiovascular pressures is presented. The relative pressure is
      calculated using the Navier-Stokes equations along user-defined lines placed
      within a time-resolved 3D phase contrast MRI dataset. The lines may be either
      straight or curved to follow an actual streamline. The technique is validated in
      an in vitro model and tested on in vivo cases of normal and abnormal transmitral
      pressure differences and intraaortic flow. The method supplements an intuitive
      visualization technique for cardiovascular flow, 3D particle trace visualization,
      with a quantifiable diagnostic parameter estimated from the same dataset.

PMID- 11323815
TI  - Assessment of a rapid clearance blood pool MR contrast medium (P792) for assays
      of microvascular characteristics in experimental breast tumors with correlations
      to histopathology.
AB  - The diagnostic potential of a new rapid clearance blood pool contrast medium
      (P792; MW = 6.47 kDa) for the MR assessment of microvessel characteristics was
      assessed in 42 chemically-induced breast tumors, with comparisons to albumin-(Gd
      DTPA). Microvessel characteristics, including the transendothelial permeability
      (K(PS)) and the fractional blood volume (fPV), were estimated by using dynamic MR
      data fit to a bidirectional two-compartment model. The MR-derived estimates for
      K(PS) and fPV using each contrast agent were compared, and assays using each
      contrast agent were correlated to the histologic tumor grade (SBR score) and the
      microvascular density (MVD) counts. Using P792-enhanced data, neither K(PS) nor
      fPV showed a statistically significant correlation with the tumor grade or the
      MVD (P >.05). Conversely, using albumin-(GdDTPA)(30), K(PS) values correlated
      significantly with the histologic tumor grade (r =.55; P <.0005) and the MVD (r
      =.34, P <.05), whereas no correlation was established for fPV. In conclusion,
      based on P792 data no correlation between tumor microvascular characteristics and
      histologic markers (SBR score or MVD) was found in this breast tumor model. Our
      analysis suggests that contrast media of relatively large (on the order of 90
      kDa) molecular size, such as albumin-(GdDTPA)(30), are more accurate for the
      characterization of tumor microvessels.

PMID- 11323816
TI  - In vivo BOLD contrast MRI mapping of subcutaneous vascular function and
      maturation: validation by intravital microscopy.
AB  - Bold contrast MRI was applied for mapping vascular maturation in tumor- and wound
      induced skin angiogenesis using the response of mature vessels to hypercapnia
      (inhalation of air vs. air 5% CO(2)) and the response of all vessels to hyperoxia
      (air 5% CO(2) vs. oxygen 5% CO(2) (carbogen)). MRI signal enhancement with
      hypercapnia was reduced in centered vs. linear phase encoding, suggesting
      increased blood flow. However, intravital microscopy demonstrated constriction of
      arterioles and reduced flux and density of red blood cells in mature capillaries
      with hypercapnia, with no change in the diameter of wound-induced neovasculature.
      The discrepancy in flow between MRI and intravital microscopy is consistent with
      increased plasma flow and reduced hematocrit. Hyperoxia resulted in increased
      blood oxygenation and constriction of all vessels. These results provide a
      hemodynamic explanation for the selective registration of MRI response to
      hypercapnia with mature vessels and the response to hyperoxia with total vascular
      function.

PMID- 11323817
TI  - Region and tissue differences of metabolites in normally aged brain using
      multislice 1H magnetic resonance spectroscopic imaging.
AB  - Quantitative measurements of regional and tissue specific concentrations of brain
      metabolites were measured in elderly subjects using multislice proton magnetic
      resonance spectroscopic imaging ((1)H MRSI). Selective k-space extrapolation and
      an inversion-recovery sequence were used to minimize lipid contamination and
      linear regression was used to account for partial volume problems. The technique
      was applied to measure the concentrations of N-acetyl aspartate (NAA), and
      creatine (Cr)- and choline (Cho)-containing compounds in cortical gray and white
      matter, and white matter lesions of the frontal and the parietal lobe in 40
      normal elderly subjects (22 females and 18 males, 56-89 years old, mean age 74 +/
      8). NAA was about 15% lower in cortical gray matter and 23% lower in white
      matter lesions when compared to normal white matter. Cr was 11% higher in
      cortical gray matter than in white matter, and also about 15% higher in the
      parietal cortex than in the frontal cortex. Cho was 28% lower in cortical gray
      matter than in white matter. Furthermore, NAA and Cr changes correlated with age.
      In conclusion, regional and tissue differences of brain metabolites must be
      considered in addition to age-related changes when interpreting (1)H MRSI data.

PMID- 11323818
TI  - Direct reconstruction of non-Cartesian k-space data using a nonuniform fast
      Fourier transform.
AB  - An algorithm of Dutt and Rokhlin (SIAM J Sci Comput 1993;14:1368-1383) for the
      computation of a fast Fourier transform (FFT) of nonuniformly-spaced data samples
      has been extended to two dimensions for application to MRI image reconstruction.
      The 2D nonuniform or generalized FFT (GFFT) was applied to the reconstruction of
      simulated MRI data collected on radially oriented sinusoidal excursions in k
      space (ROSE) and spiral k-space trajectories. The GFFT was compared to
      conventional Kaiser-Bessel kernel convolution regridding reconstruction in terms
      of image reconstruction quality and speed of computation. Images reconstructed
      with the GFFT were similar in quality to the Kaiser-Bessel kernel reconstructions
      for 256(2) pixel image reconstructions, and were more accurate for smaller 64(2)
      pixel image reconstructions. Close inspection of the GFFT reveals it to be
      equivalent to a convolution regridding method with a Gaussian kernel. The
      Gaussian kernel had been dismissed in earlier literature as nonoptimal compared
      to the Kaiser-Bessel kernel, but a theorem for the GFFT, bounding the
      approximation error, and the results of the numerical experiments presented here
      show that this dismissal was based on a nonoptimal selection of Gaussian
      function.

PMID- 11323819
TI  - Simple linear formulation for magnetostimulation specific to MRI gradient coils.
AB  - A simple linear formulation for magnetostimulation thresholds specific to MRI
      gradient coils is derived based on established hyperbolic electrostimulation
      strength vs. duration relations. Thresholds are derived in terms of the gradient
      excursion required to cause stimulation, and it is demonstrated that the
      threshold curve is a linear function of the gradient switching time. A parameter
      beta is introduced as being fundamental in the evaluation of gradient coil
      stimulation. beta is a map of the induced electric field per unit gradient slew
      rate, and can be calculated directly from the gradient coil wire pattern.
      Consideration of beta alone is sufficient to compare stimulation thresholds
      between different gradient coil designs, as well as to evaluate the expected
      dependency of stimulation threshold on position within the gradient coil. The
      linear gradient threshold curve is characterized by two parameters: SR(min) and
      DeltaG(min). SR(min) is the slope of the threshold curve and represents the
      minimum slew rate required to cause stimulation in the limit of infinite gradient
      strength. DeltaG(min) is the vertical axis intercept of the curve and represents
      the minimum gradient excursion required to cause stimulation in the limit of
      infinite slew rate. Both SR(min) and DeltaG(min) are functions of both beta and
      the standard tissue parameters E(r) (rheobase) and tau(c) (chronaxie time). The
      ease with which both the gradient system performance and the stimulation
      thresholds can be plotted on the same axes is noted and is used to introduce the
      concept of a piece-wise linear operational limit curve for a gradient system.

PMID- 11323820
TI  - Dysprosium-bearing red cells as potential transverse relaxation agents for MRI.
AB  - The cytosol of intact human red blood cells was loaded with 28.1 +/- 3.4 mM of
      dysprosium DTPA-BMA using a hypoosmotic technique. When loaded cells were diluted
      with saline and control cells to give an average dysprosium concentration of 3.3
      +/- 0.5 mM, the transverse relaxation rate constants R(*)(2) and R(2) increased.
      R(*)(2) increased from 7.5 +/- 0.9 sec(-1) to 356 +/- 50 sec(-1), and R(2)
      increased from 7.4 +/- 0.7 sec(-1) to 148 +/- 40 sec(-1). After lysing, R(*)(2)
      was 6.0 +/- 0.6 sec(-1) in the control and 13.4 +/- 1.5 sec(-1) in the mixture;
      R(2) was 6.4 +/- 1.1 sec(-1) and 9.8 +/- 2.4 sec(-1), respectively. Thus, the
      relaxivity effects were enhanced by sequestration of the dysprosium within intact
      red cells, and this effect was lost after lysis. At a circulating whole-blood
      concentration of 0.81 +/- 0.15 mM in rats, the liver signal intensity dropped
      29.9% +/- 3.7% and kidney signal intensity dropped 19.4% +/- 8.7%. Dysprosium
      loaded cells might be useful in the study of perfusion and tissue blood volume.

PMID- 11323821
TI  - Assessment of the effect of 2-chloroadenosine in normal rat brain using spin
      labeled MRI measurement of perfusion.
AB  - Adenosine analogs such as 2-chloroadenosine are potent cerebrovasodilators. Spin
      labeled MRI was used to investigate the spatial distribution, dose-response, and
      timing of the effect of 2-chloroadenosine on cerebral blood flow (CBF) after
      intraparenchymal injection into rat brain. Sprague-Dawley rats (N = 10) were
      injected with 2-chloroadenosine at doses of 0.3, 6.0, or 12 nmoles, or saline
      vehicle (2-4 microL). CBF was serially quantified in a slice through the
      injection site in a circular (3.6 mm diameter) region of interest (ROI) around
      the injection and in ipsilateral hemispheric ROIs at approximately 90 min and
      approximately 180 min. Marked 3.77- and 3.93-fold increases in CBF (vs. vehicle)
      were seen in the circular ROI at approximately 90 min and approximately 180 min
      after 12-nmol injection, respectively. Similarly, 2.92- and 2.78-fold increases
      in hemispheric CBF were observed at approximately 90 min and approximately 180
      min, respectively, after injection of 12 nmoles. Linear dose-response
      relationships were observed at both times after injection in both ROIs (all P <
      0.01). Spin-labeling MRI assessment revealed that parenchymal injection of 2
      chloroadenosine produces potent, dose-dependent, and sustained vasodilation over
      large areas of brain. This treatment and imaging paradigm should facilitate
      investigation of the effect of CBF promotion in models of traumatic and ischemic
      brain injury.

PMID- 11323822
TI  - Single-shot T2(*) measurement to establish optimum echo time for fMRI: studies of
      the visual, motor, and auditory cortices at 3.0 T.
AB  - The signal change in fMRI is dependent on the echo time and the rate of decay of
      transverse magnetization. The latter factor may vary across regions of the brain
      as a result of variations in field homogeneity. Previous measurements of the
      signal change with echo time have generally employed relatively slow multi-echo
      techniques, which may be sensitive to movement and habituation effects. Here a
      fast T(2)(*) measurement technique, involving the generation of six low
      resolution echo planar images from a single FID, is described, and its use in the
      evaluation of the optimum echo time for visual, motor, and auditory fMRI
      experiments at 3.0 T is outlined.

PMID- 11323823
TI  - Shade selection and value control.
AB  - The purpose of this article is to describe, in general terms, the variables that
      may influence the accurate assessment of shade selection prior to the fabrication
      of a ceramic restoration, and to outline a specific procedure for "shade
      selection," to determine the appropriate porcelain powders used in recreating the
      desired optical properties of the natural dentition. Special attention is
      dedicated to the control of the 'value' level, which is of paramount importance
      in achieving a vital, life-like appearance that is in harmony with surrounding
      dentition. By controlling and maintaining one light source, we can eliminate at
      least one variable in the shade taking process. By identifying the location of
      the individual components utilized to re-create natural dentition, one may render
      greater overall accuracy in shade reproduction. Understanding the limitations of
      standard shade guides, and increasing color communication with the use of custom
      shade guides has distinct advantages for achieving desired shades.

PMID- 11323824
TI  - Refining of dental scrap: physical characterization and sampling.

PMID- 11323825
TI  - Understanding market capitalization.

PMID- 11323826
TI  - Congressional maneuvering fails; ergonomics standard published.

PMID- 11323827
TI  - Communications for the year 2000 and beyond.

PMID- 11323828
TI  - Prevalence of noncarious cervical lesions and their relation to occlusal aspects:
      a clinical study.
AB  - PURPOSE: The purpose of this study was to assess noncarious cervical lesions in
      young patients and to establish a possible relation with occlusal aspects.
      MATERIALS AND METHODS: Forty-eight dental students (28 males; 20 females) between
      the ages of 16 and 24 years, were investigated to verify the presence of
      noncarious cervical lesions and their relation to some occlusal aspects. The
      assessment involved a questionnaire, clinical examinations, and model analysis.
      RESULTS: The results indicated that the lower first molars (21.3%), the upper
      first molars (16.0%), the upper first premolars (12.8%), the lower first
      premolars (11.7%), and the lower second premolars (11.7%) were the teeth most
      affected by the lesions. Age was a significant factor with respect to the
      presence of lesions; the students with noncarious cervical lesions were older
      than the students who showed no lesions. Among the 79 teeth exhibiting lesions,
      62 (78.5%) showed wear facets. In the group with lesions, the mean, per subject,
      was 15.0 teeth with wear facets, whereas in the group without lesions the mean
      was 10.8 teeth with wear facets per subject, suggesting that occlusal stress has
      some effect on lesion development.

PMID- 11323829
TI  - Follow-up evaluation of a series of dentin-bonded ceramic restorations.
AB  - PURPOSE: The results of a retrospective evaluation of 60 dentin-bonded full
      coverage restorations with an average time in service of 2.4 years previously
      have been reported. The purpose of this study was to evaluate the crowns after a
      further 2 years in service. MATERIALS AND METHODS: The 23 patients in the initial
      study whose restorations were found to be intact in June 1996 were contacted by
      mail and invited to present for review in October 1998. The restorations of 20
      respondents were assessed by two examiners using modified United States Public
      Health Service criteria. RESULTS: The patients had received a total of 53
      restorations (mean age of restorations, 4.4 years; range, 5.5-3 yr). At the time
      of examination, 48 restorations were found to be intact. No secondary caries was
      detected in these restorations, and optimal scores for gingival health, anatomic
      form, and marginal discoloration were recorded for 39, 47, and 33 crowns,
      respectively. Color match was assessed as being very good in 43 of the 48
      restorations assessed. The reasons for replacement of the failed restorations
      were gingival recession (n = 1), restoration fracture (n = 1), core fracture (n =
      1), and unknown (n = 2). Each patient's perception of his or her restorations was
      recorded by means of a questionnaire, with the responses indicating that all but
      two patients were satisfied. Only one patient had experienced any discomfort.

PMID- 11323830
TI  - Effect of stepped light intensity on polymerization force and conversion in a
      photoactivated composite.
AB  - PURPOSE: This study evaluated the effect of stepped light intensity on the
      polymerization shrinkage forces and degrees of conversion of a hybrid composite.
      MATERIALS AND METHODS: Composite specimens were bonded between two steel rods
      (5.00 mm diameter, 1.25 mm apart, configuration factor = 2) mounted in a
      universal testing machine using a constant displacement mode. Polymerization
      contraction force was recorded for 300 seconds under four light exposure
      conditions: group 1: 40 s x 800 mW/cm2; group 2: 10 s x 100 mW/cm2 + 30 s x 800
      mW/cm2; group 3: 60 s x 800 mW/cm2; group 4: 10 s x 100 mW/cm2 + 50 s x 800
      mW/cm2. Maximum curing force (N300 s) and maximum force rate of the four groups
      were compared using one-way analysis of variance (ANOVA) (alpha = 0.05) and the
      Tukey test. Degree of conversion in all groups was evaluated at two depths (top
      surface and 2 mm) using Fourier transform infrared spectroscopy (FTIR). RESULTS:
      Mean maximum shrinkage forces and standard deviations (SD) were: group 1, 177 N
      (SD = 23); group 2, 172 N (SD = 11); group 3, 213 N (SD = 15); group 4, 197 N (SD
      = 17). Mean maximum forces for stepped and standard groups with the same duration
      (1 and 2; 3 and 4) were not statistically different; means for groups 2 and 3
      were statistically different. Maximum force rates were not significantly
      different (p = .1548). Force:time curves were S-shaped. Specimens exposed to
      stepped curing exhibited longer delays before force was recorded. Mode of curing
      was shown not to contribute to overall cure, but both duration of cure and the
      depth (top surface vs. 2.00 mm) were significant with an interaction effect.

PMID- 11323832
TI  - Removal of porcelain veneers aided by a fluorescing luting cement.
AB  - PURPOSE: Porcelain veneers are a safe and effective treatment modality for
      selected teeth that have poor esthetics. However, removal of porcelain veneers
      that have failed may be time-consuming and involve considerable removal of sound
      tooth structure adjacent to the veneer. The aim of this study was to evaluate a
      novel method of porcelain laminate veneer removal by incorporating a fluorescent
      dye into the luting cement that allows the practitioner to visualize the cement
      on the tooth and remove the veneer without causing residual damage to the
      adjacent tooth substance. MATERIALS AND METHODS: Porcelain veneers were luted on
      extracted teeth with a luting cement modified with a fluorescing agent. Faculty
      teaching staff and final year dental undergraduates were asked to remove the
      veneers with the aid of a curing light to render the luting cement visible by
      fluorescing. They were then asked to compare the removal of comparable veneers
      without this visual aid and to complete a standard questionnaire. The depth of
      cure of the conventional and modified cements was measured using a penetrometer.
      RESULTS: Results of the questionnaire indicated that the operators found removing
      the veneer cemented with the modified (fluorescing) cement considerably easier
      than removing the veneer cemented with the conventional cement. Microscopy
      indicated that more damage was caused to the underlying tooth during removal of
      conventionally cemented veneers. The incorporation of the dye into the cement
      reduced the depth of cure from 4.238 mm (SD = 0.025) to 3.761 mm (SD = 0.096).

PMID- 11323831
TI  - Effect of whitening agents containing carbamide peroxide on cariogenic bacteria.
AB  - PURPOSE: The purpose of this study was to investigate the in vitro antibacterial
      effects of three different carbamide peroxide products (Nitewhite, Opalescence,
      and Proxigel) on cariogenic microorganisms (mutans streptococci [MS] and
      lactobacilli), and to evaluate the effects of a 10% carbamide peroxide solution
      (Proxigel) on salivary levels of MS and lactobacilli clinically. MATERIALS AND
      METHODS: Growth inhibition studies were performed to determine the concentration
      and exposure time of carbamide peroxide to give total inhibition of recoverable
      growth of MS and lactobacilli. Paraffin-stimulated saliva samples were collected
      from subjects before and after 6 weeks of treatment with 10% carbamide peroxide
      in bleaching trays, and levels of MS and lactobacilli were determined. RESULTS:
      The growth inhibition studies showed no visible growth of MS or lactobacilli at
      24-, 48-, or 72-hour incubation, after a 2-hour exposure to 1% carbamide
      peroxide. Identical results were obtained with all three carbamide peroxide
      products. In the clinical study, the mean salivary MS levels, expressed as
      logarithm colony-forming units per milliliter (CFU/mL), were 5.38 for the
      pretreatment samples and 5.23 for the post-treatment samples. The differences
      were not statistically significant (p > .05). However, there was a reduction in
      logarithm lactobacilli counts from a mean of 4.12 pretreatment to a mean of 2.74
      post-treatment. This was statistically significant (p < .05).

PMID- 11323833
TI  - The soft tissue paradigm in orthodontic diagnosis and treatment planning: a new
      view for a new century.

PMID- 11323834
TI  - Restoration of extensive erosion areas using an indirect composite technique.
AB  - Cervical erosion defects, particularly those of extensive size that are located
      in an area where control of the operative field is difficult, can present a
      significant restorative challenge. This article describes an indirect restorative
      technique to solve this problem. Following tooth preparation, an indirect
      restoration is luted to the tooth and the margins are finished and polished.
      Using an indirect technique minimizes operative field isolation time and the
      total chairside time required to restore the tooth. Clinical cases are presented
      to illustrate this technique.

PMID- 11323835
TI  - Teledentistry:Genesis, actualization and caveats.

PMID- 11323836
TI  - Teledentistry: what is it now, and what will it be tomorrow?
AB  - A few years ago, teledentistry involved calling an expert on the telephone for
      advice. Now it involves consulting experts using the Internet. This article
      explains the basic ideas underlying teledentistry. It involves the local dentist
      digitizing and electronically transmitting drawings, diagrams, photographs, and X
      rays to a specialist. Along with these data, the dentist will most likely need to
      fill out a standard consult form from the specialist's Web site. In return, the
      specialist will develop and return a confidential consultation report to the
      dentist or physician requesting help. For this service, a time-based fee will be
      paid to the expert. Unfortunately, it is likely that some doctors will use the
      Internet to set up and seek direct patient contact, thus becoming
      "cyberdentists." In most cases, cyberdentistry will not be in the best interests
      of the public. However, teledentistry should not only be a practice builder for
      the local dentist, but also has the potential for helping dentists better serve
      their patients while increasing their own knowledge.

PMID- 11323837
TI  - Virtual health care: unresolved legal issues.
AB  - As online health care begins to look more like the practice of medicine, a range
      of legal questions has emerged. This article examines issues of concern to both
      Internet users and health care practitioners, focusing in particular on the laws
      relating to negligence and disclaimers. It concludes that interactive contact
      between doctor and patient in cyberspace may very well be viewed by the courts as
      akin to the practice of health care and that the typical disclaimer may not
      insulate practitioners from liability.

PMID- 11323839
TI  - The future of teledentistry.
AB  - Teledentistry is a rapidly forming subset of telehealth, a field that already has
      considerable impact on the health care industry. Recent advances have created new
      opportunities for teledentistry, and changes in diverse technologies have created
      new tools for the practitioner. Technologies currently available are beginning to
      change the dynamics of dental care delivery. As teledentistry evolves, it will
      offer new opportunities to improve the level of patient care and reshape current
      business models.

PMID- 11323838
TI  - Rural dentistry: opportunities for the next millennium in fixed and mobile
      practices.
AB  - Many dentists assume that practice in California's rural counties would be
      hindered by lower income potential, professional isolation, and lack of
      specialists for assistance. The evidence suggests otherwise, however. Income data
      show that the population of many rural counties can well afford dental care. In
      addition, new uses of the Internet for teleconsulting and idea exchange has the
      potential for reducing isolation and providing access to specialized knowledge.
      Particularly for those practitioners who enjoy the rural lifestyle, such counties
      offer excellent potential for dental practice.

PMID- 11323840
TI  - E-mail-based oral medicine consultation.
AB  - A pilot study was undertaken to assess whether text-based electronic patient data
      transmission (e-mail) is a reliable source of information for the diagnostic
      decision-making process. The main objective was to determine if information
      contained within a transmitted text could be reliably used as basis for making
      general recommendations for diagnostic tests and follow-up or referral plans
      pertaining to a variety of oral mucosal pathologic conditions. The results
      suggest that face-to-face patient examination is more accurate in establishing a
      correct diagnosis for oral mucosal pathologies than transmitted descriptive
      patient data alone.

PMID- 11323841
TI  - Anger management.

PMID- 11323842
TI  - On the cusp of scrutiny again.

PMID- 11323843
TI  - Evidence-based dentistry: a new tool for clinical decision-making.

PMID- 11323844
TI  - Dental student debt looms large.

PMID- 11323845
TI  - Increase profits and save time creating the perfect provisional restorations.

PMID- 11323846
TI  - Model work: dentistry's ignored stepchild.

PMID- 11323847
TI  - The rippling effect of communication.

PMID- 11323848
TI  - Ancient toothpicks point to evidence of early meat-eating hominids.

PMID- 11323849
TI  - Given the recent controversy concerning beryllium, what should be our concerns or
      not be our concerns as dental lab managers? He would like to hear other opinions
      in the industry or any problems encountered by others.

PMID- 11323850
TI  - Legislation would make denturism legal in Missouri.

PMID- 11323851
TI  - Quantifiable risk in dentistry--a letter to the profession.
AB  - Recent attention to certain worries such as the AIDS "epidemic," biofilms in
      dental unit water lines, and hepatitis C have resulted in unbalanced and often
      inappropriate action by dentists and public health authorities. These actions
      include exaggerating, underestimating, and ignoring risks in the dental
      environment. To be effective and responsible practitioners, we must recognize
      reality and proportion, concentrate resources on the greatest problems, and seek
      dependable epidemiology. Infection control issues are an important application
      for this form of evidence-based science.

PMID- 11323852
TI  - Syncope.

PMID- 11323853
TI  - Dental practitioner compliance with the AHA bacterial endocarditis prophylaxis
      recommendations.

PMID- 11323854
TI  - Is periodontitis genetic? The answer may be Yes!
AB  - Specific bacteria cause periodontitis by activating immuno-inflammatory responses
      in the tissues. There are certain risk factors that significantly affect the
      disease process by altering the immuno-inflammatory response and increasing the
      likelihood of severe periodontitis. These risk factors are smoking, diabetes, IL
      1 genotype, and perhaps others. Today about 20 percent of the population smokes
      at a level that should make a difference relative to periodontitis. About 30 to
      33 percent of the Caucasian population is IL-1 genotype positive. There are
      compelling reasons to look at these risk factors in your practice to help
      formulate a complete treatment plan for your patients.

PMID- 11323855
TI  - Helping reduce medical errors.

PMID- 11323857
TI  - Identifying dentures.

PMID- 11323856
TI  - Arterio-venous fistula of the internal maxillary artery. A clinico-pathologic
      presentation.

PMID- 11323858
TI  - Drastic changes in what today's dental students are taught is right on.

PMID- 11323859
TI  - Avoiding the challenges of emerging infectious disease and antibiotic resistance.

PMID- 11323860
TI  - Our future in restorative dental materials.
AB  - Restorative dentistry is moving toward more extensive diagnosis, caries risk
      assessment, and non-invasive caries management. There will be less restorative
      intervention and more conservation of existing tooth structure whenever possible.
      Prevention, minimal intervention, and restoration maintenance will be key
      guidelines. Restorative materials will continue to evolve slowly and steadily
      (Figure 1). However, most of the guiding principles for cavity preparation and
      restoration will be the same as they have been for the past decade. During the
      coming decade, practitioners will see the first evidence of tooth replacement
      with genetically equivalent teeth.

PMID- 11323861
TI  - Enamel etching.

PMID- 11323862
TI  - Small-diameter implants: indications and contraindications.
AB  - The choice of implant diameter depends on the type of edentulousness, the volume
      of the residual bone, the amount of space available for the prosthetic
      reconstruction, the emergence profile, and the type of occlusion. Small-diameter
      implants are indicated in specific clinical situations, for example, where there
      is reduced interradicular bone or a thin alveolar crest, and for the replacement
      of teeth with small cervical diameter. Before using a small-diameter implant, the
      biomechanical risk factors must be carefully analyzed. Preliminary reports of
      this type of implant show good short- and medium-term results.

PMID- 11323863
TI  - Scientifically based rationale and protocol for use of modern indirect resin
      inlays and onlays.
AB  - The desire to place esthetically pleasing, conservative, functionally stable,
      posterior restorative materials has steadily increased over the past 20 years.
      The creation of successful dentin bonding adhesives and appropriate resin luting
      cements has paved the way for the development of a myriad of indirect resin-based
      restorative materials. These materials have been specifically designed to
      overcome the negative attributes of their porcelain counterparts, and to simplify
      fabrication, insertion, and post-delivery adjustments. Possibly like no other
      product before, these restorative materials have met with instant clinical
      acceptance by many practitioners, and concern exists that these materials have
      not been sufficiently studied to warrant such widespread acceptance. This article
      presents an overview of the history and development of resin-based, esthetic,
      indirect systems, and offers the clinician a review of the literature supporting
      their role in posterior restorative dentistry. Additionally, a scientifically
      based protocol for preparation, impressing, provisionalization, and subsequent
      cementation and adjustment of indirect laboratory-processed resin inlays and
      onlays is presented.

PMID- 11323864
TI  - In vitro evaluation of margins of replaced resin-based composite restorations.
AB  - PURPOSE: To evaluate in vitro any increase in size of Class V resin-based
      composite (RBC) restorations as a result of replacement. MATERIALS AND METHODS:
      For group 1, 20 Class V cavity preparations were prepared in extracted incisor
      and canine teeth. The cavosurface margin was prepared as a butt joint 90-degree
      angle toward the occlusal wall. Impressions were made of all preparations with a
      polyvinyl siloxane material. The cavities then received a 1.5-mm 45-degree bevel
      at the cavosurface margin of the occlusal wall. Impressions were again made of
      the preparations. The cavities were then restored with a conventional multistep
      bonding system (Scotchbond Multi-Purpose, 3M Dental Products, St. Paul,
      Minnesota) and a microfilled RBC (Silux Plus, 3M Dental Products). As a second
      part of the study (group 2), another 20 Class V cavity preparations were
      prepared. Half of the cavities received a bevel at the cavosurface margin of the
      occlusal wall, and half were finished with a butt joint. Impressions were made
      from all 20 specimens followed by resin-based composite restoration in the same
      manner as previously described. All the restorations from both group 1 and group
      2 were then removed with carbide burs. New impressions were made, and 100 stone
      models were fabricated. The perimeter and area of the cavity preparations,
      including the beveled area, were recorded using a video-based imaging system
      equipped with macro lens, at 10 to 15 times magnification. Both perimeter and
      area of the postoperative cavity preparation were compared to the initial cavity
      size for both butt joint and bevel finishing. RESULTS: Intraclass correlation
      coefficient and paired t-test showed no significant difference between the
      preoperative bevel type of cavity preparation and its postoperative counterparts
      for both group 1 and group 2 (p > .05). However, a significant increase in the
      size of the cavity preparation was found preoperatively when a bevel was placed
      at the cavosurface margin. Postoperatively, a significant increase in size of the
      cavities was found for butt joint type finishing for both area (p = .0001) and
      perimeter (p = .0001), compared to initial cavity size.

PMID- 11323866
TI  - Expanded duty assistants.

PMID- 11323865
TI  - Properties of packable dental composites.
AB  - The introduction of many new packable composites suggests that these products are
      rapidly gaining popularity. The purpose of this study was to evaluate the in
      vitro properties of a variety of packable composites and to determine if
      significant enhancements in physical and mechanical properties have been achieved
      for these materials compared with two popular nonpackable posterior composites.
      For the five packable and two regular composites tested (ALERT, Pyramid-Dentin,
      Pyramid-Enamel, Solitaire, SureFil, Heliomolar, and Z100), the values for
      fracture toughness, flexure strength, flexure modulus, hardness, and volumetric
      polymerization shrinkage were determined. In general, although the packable
      composites were of heavier consistency, they had mechanical properties that were
      intermediate to (ALERT, Pyramid, and SureFil) or lower than (Solitaire) those of
      the nonpackable materials. These results could have been predicted based on the
      similar methacrylate resin chemistry and filler volumes of the various
      composites. No composite had adequate depth-of-cure when tested in increments
      greater than 2 mm thick. Polymerization contraction of the packable composites
      was similar to or higher than that of the nonpackable composites. In addition,
      the radiopacity of at least one material, Solitaire, was not considered to be
      adequate (less than 2 mm of aluminum). The results of this study suggest that
      these packable composites are unlikely to offer improved clinical performance
      over well-placed nonpackable composites.

PMID- 11323867
TI  - A review and update on HIV infection and the AIDS epidemic in the adolescent and
      adult.

PMID- 11323868
TI  - The Dr. Jack E. Wells Memorial Dedication to Dentistry Award goes to Dr. William
      F. Slagle.

PMID- 11323869
TI  - Teen health crisis has dental implications.

PMID- 11323870
TI  - Dental implications of the Human Genome Project.

PMID- 11323871
TI  - A pragmatic perspective on reconstructive dentistry and the utilization of
      posterior all-ceramic crowns.
AB  - The placement of well over 500 units of all-ceramic crowns with internally
      supported aluminous porcelain cores, on anterior (37 percent) and posterior (63
      percent) teeth, has demonstrated no greater fracture rate than what might be
      expected from ceramometal crowns. This esthetic option further expands
      reconstructive vistas. However, this option must be accompanied by inclusive
      patient management and education, proper examination and integrated comprehensive
      treatment planning based upon a sound knowledge of the biology and biomechanics
      of the stomatognathic system.

PMID- 11323872
TI  - Salaries and benefits of dental hygienists in Tennessee.
AB  - Salaries and benefits are a major concern for dental hygienists and their
      employers. In 1998, the University of Tennessee Dental Hygiene Department
      conducted a survey of dental hygienists licensed to practice in Tennessee.
      Objectives included (1) to determine the current salary range and benefits of
      practicing dental hygienists, (2) to determine the factors which influence
      salaries and benefits, and (3) to compare the salaries and benefits of dental
      hygienists across the state. Results revealed an average compensation of $175.00
      per day. While most full-time dental hygienists receive paid vacation, only 33
      percent receive health care benefits. There were various factors influencing
      salaries and benefits, including the method of compensation, region of the state
      in which one practices, years of experience, and ethnic background.

PMID- 11323873
TI  - Rehabilitation of a patient with an implant-supported auricular prosthesis.

PMID- 11323874
TI  - Clinicopathologic correlation quiz: persistent ulcerations of the palate.

PMID- 11323875
TI  - Dentistry: Y2K and beyond.

PMID- 11323876
TI  - Class II correction in transitional dentition.
AB  - Correcting the developing Class II malocclusion and preventing abnormal
      relationship of the jaws and occlusal dysfunction by repositioning the permanent
      molars and incisors is a significant benefit to the growing child. Future
      orthodontic therapy is significantly reduced often to detailing or eliminated in
      some cases.

PMID- 11323877
TI  - The Controlled Arch System: a new method of straightwire treatment (Part II).

PMID- 11323878
TI  - Cast posts that fit at first try.
AB  - The following article describes a procedure that permits the retention of a cast
      post that will fit passively in the canal at first try. By means of an indirect
      method, an elastic cast was poured in the master impression and an exact
      duplicate of the future dowel was formed with self-curing acrylic resin. A stone
      cast made from a second pour of the impression was then used to adjust the
      pattern in the laboratory. Posts made with the use of this system routinely sit
      passively in the root canal without the need of adjustments at the chair. The
      interval employed in obtaining and adjusting an acrylic resin pattern mentioned
      in the above way represents less time and effort than trying to make a cast fit
      in the canal, especially in the case of patients who require multiple posts in
      the same arch.

PMID- 11323879
TI  - 'Fluxes' and chemical solubility in dental porcelains.
AB  - Materials such as sodium, potassium, magnesium, and calcium oxides are routinely
      added to glasses commonly called "fluxes." These materials act as modifiers that
      disrupt the network arrangement of atoms in glasses and are used to optimize
      their fusion, expansion, or chemical properties. Dental porcelains are made of
      glasses and ceramic components such as leucite. The international standards ISO
      6872 and ISO 9693 mandate a chemical solubility test, in which a solubility limit
      (< 100 g/cm2 for the test) is set for dental porcelains. Dental porcelains that
      have passed this test are very stable in the oral environment and lose very small
      amounts of porcelain to dissolution by saliva. The oxides that leach from these
      porcelains are relatively benign, and are usually absorbed through the average
      diet in much larger quantities. In addition to these factors, the long and
      successful clinical history of restorations made out of dental porcelains is a
      strong argument for their safety and efficacy, when used in accordance to
      indications and recommended techniques.

PMID- 11323880
TI  - Take your communications seriously.

PMID- 11323881
TI  - E-schemes and E-scams: what investors should know about Internet investment
      fraud.

PMID- 11323882
TI  - Shade verification action in Florida and a clarification of South Carolina's
      registration requirement.

PMID- 11323883
TI  - 1999 bills affecting dentistry become law: a report.

PMID- 11323884
TI  - Market place issues. What the MDA is doing.

PMID- 11323885
TI  - "Taking care of business". Interview by William R. Chase.

PMID- 11323886
TI  - Extracoronal precision attachments for removable partial dentures.

PMID- 11323888
TI  - How "abundance thinking" can change your life.

PMID- 11323887
TI  - Alveolar bone loss and estrogen deficiency.

PMID- 11323889
TI  - Next up: National Children's Dental Health Month.

PMID- 11323890
TI  - ADA House of Delegates: report from Hawaii.

PMID- 11323891
TI  - House, Senate at work on health issues affecting dentists.

PMID- 11323892
TI  - Dealing with a no-fault auto insurance carrier.

PMID- 11323893
TI  - Building the high-profit, quality dental practice.

PMID- 11323894
TI  - Dental electronic claims: navigating through the hoopla.

PMID- 11323895
TI  - In recognition of National Children's Dental Health Month.

PMID- 11323896
TI  - Let's celebrate National Children's Dental Health Month!

PMID- 11323897
TI  - Mouthguards: preventing sports-related injuries.

PMID- 11323898
TI  - Trauma to the primary and young permanent dentitions.
AB  - It is the responsibility of the dentist to stay current on the latest techniques
      available to treat traumatic injuries. The charts included provide most of the
      potential emergency treatment possibilities, recommended follow-up treatment, and
      final treatment outcomes essential to providing the best care for our child
      patients. It is also the responsibility of the dentist to use evidence-based
      research when adopting treatment protocols. It is not appropriate to use
      anecdotal or single case studies as a basis for adopting treatment protocols. It
      is very difficult in this area of trauma to come up with good scientific research
      with adequate sample sizes and long-term data. Dr. J.O. Andreasen has excellent
      compiled long-term research on trauma. His books, Essentials of Traumatic
      Injuries to the Teeth and An Atlas of Replantation and Transplantation of Teeth
      are two very good books for any clinical practice.

PMID- 11323899
TI  - Salivary markers: their role in breast cancer detection.

PMID- 11323900
TI  - Another national data bank.

PMID- 11323901
TI  - Be a plastic surgeon.

PMID- 11323902
TI  - Authorship of peer-reviewed journal publications.

PMID- 11323903
TI  - Top issues for this year's legislature.

PMID- 11323904
TI  - Dental records: histories, retention and identification.

PMID- 11323905
TI  - New life, disability and long-term care options introduced.

PMID- 11323906
TI  - Quality of life. See your vision, live your dream.

PMID- 11323907
TI  - A 10-step program towards wellness and dentistry.

PMID- 11323908
TI  - Stress and human spirituality: at the crossroads of mind-body-spirit healing.

PMID- 11323909
TI  - How do you define "quality of life"?

PMID- 11323910
TI  - A new household plan for getting the most out of life.

PMID- 11323911
TI  - MDA dental Medicaid analysis points to "crisis".

PMID- 11323913
TI  - Surgical template fabrication.

PMID- 11323912
TI  - Creating esthetic composite restorations.
AB  - The purpose of this article is to describe a fabrication technique to assist
      dental technicians creating esthetic indirect composite restorations. After the
      teeth have been prepared and the models completed, the technician can begin the
      fabrication process. Translucent dentin is selected to reduce opacity and enhance
      the blend with the remaining dentition. High chroma modifiers can then be placed
      into the fossa area to replicate dentin seen in natural dentition. Different
      incisal materials can then be layered into the build-up to regulate the value of
      the restoration. Special effects such as hypocalcification are placed internally
      to mimic naturally occurring esthetics. Realistic anatomy is created using a
      small-tipped instrument directly into the final layer of uncured enamel material.
      Fissure characterization is placed in the restoration to match existing
      dentition. Fit and margins are verified on separate dies to minimize
      discrepancies. Path of insertion and proximal contacts are established on a solid
      model to minimize chairside adjustments.

PMID- 11323914
TI  - Toothbrush technology--even the Pharoahs brushed their teeth.

PMID- 11323916
TI  - What is the best technique to rebase a complete denture?

PMID- 11323915
TI  - What would be your thoughts of base metals to silver palladium in the mouth and
      in the cost factor?

PMID- 11323917
TI  - Kentucky legislature releases study on denturism.
AB  - The Kentucky study goes on to discuss the economic issues surrounding denturism,
      including the cost of dentures, insurance coverage and governmental savings
      through Medicaid. The report also includes a section on public health issues.
      That section covers competency, analysis of risks and oral health. The final
      section of the research study explores the various policy options open to the
      Kentucky General Assembly.

PMID- 11323918
TI  - A commitment to change.

PMID- 11323919
TI  - NIDCR research: changing the face of dentistry.

PMID- 11323921
TI  - Managing the patient-centered practice.

PMID- 11323920
TI  - Business systems: the key to dental practice success.
AB  - The future of dentistry will be similar to that of many other businesses. It will
      be faced radical changes, new ways of thinking, new services, and greater
      competition. As these factors occur in all businesses, it will be those with
      systems and outstanding customer service that are able to not only survive, but
      also to thrive. Achieving practice success will be tied to having effective and
      efficient business systems, including customer service. While the world is
      changing rapidly, basic business principles and human nature have not changed.
      While businesses continue to work toward maximum productivity and profitability,
      patients will want to continue being treated with the greatest service and
      respect. The future may bring a gradual shift in dental practices. The top 20
      percent of practices in five to seven years will have higher profitability than
      the top 5 percent of practices do today. On the other hand, the other 80 percent
      of dental practices will actually have decreased profitability. The difference
      will be that the top 20 percent of practices will implement outstanding business
      systems that allow them to be more efficient and effective than ever before. They
      will implement many new services of both traditional needs-based dentistry and of
      an elective nature. These practices are preparing today for the future regardless
      of the effects of the economy or changes in dental insurance or health care
      regulations.

PMID- 11323922
TI  - The patient-centered practice.

PMID- 11323923
TI  - Hiring and maintaining a winning dental team.

PMID- 11323924
TI  - The hygiene department in the contemporary general practice.

PMID- 11323925
TI  - Creating value: partner with your patient.

PMID- 11323926
TI  - The dentist's dirty secret.

PMID- 11323927
TI  - Implant procedures 101.
AB  - Many practitioners have found implant procedures to be too difficult or too much
      trouble to perform. Now that restorative components for most implant systems
      allow for cemented restorations, implant procedures for most clinical situations
      can be completed in two or three one-hour appointments. This article will review
      an easy-to-follow restorative philosophy using single- and two-to-three-unit
      implant restorative procedures that are similar to conventional dental
      procedures.

PMID- 11323928
TI  - Observations on achieving total practice success.
AB  - A doctor or group practice that understands the design of what the practice wants
      to be and develops a strategy to accomplish that end will invariably achieve a
      high level of performance. Performance areas in contemporary practice
      administration cover a wide area including growth, transition, and succession.
      Due to the wide and demanding areas in practice administration, it is important
      to address any practice planning effort in a comprehensive manner rather than a
      piecemeal approach. The foregoing will materially assist any practitioner to
      achieve the level of success they seek.

PMID- 11323929
TI  - Crown lengthening to facilitate restorative treatment in the presence of
      incomplete passive eruption.
AB  - Crown-lengthening surgery can be utilized to expose subgingival caries. In this
      clinical case, a patient presented with incomplete passive eruption in the
      maxillary anterior sextant. This case illustrates that when incomplete passive
      eruption is present and restorative treatment is necessary in the maxillary
      anterior sextant, crown-lengthening surgery not only provides exposure of
      subgingival caries but can also result in a more esthetic therapeutic outcome.

PMID- 11323931
TI  - The pilot scheme for vocational training for dentists in the Republic began last
      September.

PMID- 11323930
TI  - Customized abutments to shape and transfer peri-implant soft-tissue contours.
AB  - With the functional successes of implant therapy being realized, the emphasis is
      shifting to the creation of tooth-like esthetics with implant therapy. Dental
      implants are placed after careful planning and site preparation, which may
      include bone and soft tissue grafting. The final soft tissue appearance is
      enhanced through the early use of provisional restorations. A combination
      technique is described to fabricate provisional healing abutments for cement-on
      prostheses and to transfer the individualized peri-implant soft-tissue contours
      to the dental laboratory. This technique will allow the practitioner to deliver
      highly customized implant care with familiar techniques and readily available
      materials.

PMID- 11323932
TI  - Tobacco and oral diseases--report of EU Working Group, 1999.
AB  - Smoking often results in discolourations of teeth and dental restorations.
      Halitosis, diminished taste and smell acuity are common side effects of smoking.
      Periodontal disease is increased both in prevalence and severity in smokers.
      Smoking cessation may halt the disease progression and improve the outcome of
      periodontal treatment. Oral cancer and precancer occurs much more frequently in
      smokers than in non-smokers. Smoking cessation significantly decreases the
      increased risk of oral cancer within 5-10 years. Dental implant failure rates are
      significantly higher in smokers than in non-smokers. The entire dental team
      should be aware of the relationship between smoking and dental problems and
      should convey the message that non-smoking is the norm. Smoking counselling
      should be a fundamental part of the dental curriculum and any practice prevention
      programme.

PMID- 11323933
TI  - An unusual case of denture--induced hyperplasia.

PMID- 11323934
TI  - Dental overseas voluntary elective.

PMID- 11323935
TI  - Resolution of gingival overgrowth following change from cyclosporin to tacrolimus
      therapy in a renal transplant patient.
AB  - Gingival overgrowth is a well documented and common side-effect of cyclosporin
      therapy. Gingival swelling in this condition hinders efficient oral hygiene and
      is of aesthetic concern to patients. This case report outlines rapid and dramatic
      reduction in overgrowth when tacrolimus replaced cyclosporin as the
      immunosuppressive agent in a renal transplant patient with established
      overgrowth.

PMID- 11323936
TI  - Water fluoridation, tooth decay, safety and health.

PMID- 11323937
TI  - Oral health in Ireland.

PMID- 11323939
TI  - Dental plaque revisited--oral biofilms in health and disease.

PMID- 11323938
TI  - Communication between dentists and laboratory technicians.
AB  - A questionnaire was sent to 29 laboratory technicians regarding prescription
      writing by dentists for single anterior maxillary unit metal ceramic prostheses.
      Sixty nine per cent of the technicians responded and of these 40 per cent
      included copies of the typical prescriptions they receive. The results clearly
      showed that the standard of communication between dentist and laboratory
      technician is inadequate, although it has improved over recent years. The
      effectiveness of the Medical Devices Directive legislation was considered by
      reviewing the prescription sheets. It was concluded that many technicians still
      rely on contacting the prescribing dentist by telephone to clarify instructions
      and are often forced to make decisions without the necessary information. The
      finer details of prosthesis construction were found to be the weakest area of
      prescription writing. Time pressure was deemed the single greatest impediment to
      a harmonious working relationship. The recommendations of this paper are based on
      improving the levels of communication between these two members of the dental
      team. It is proposed that dentists should increase their awareness of the
      laboratory environment by maintaining closer links with their technicians. This
      would not only expand their understanding and appreciation of the laboratory
      environment, but also give the opportunity for discussing new developments in
      dental technology. Further undergraduate training in the area of laboratory
      prescription writing is also recommended.

PMID- 11323940
TI  - The medical management of masseteric hypertrophy with botulinum toxin.
AB  - The authors present a series of cases of masseteric hypertrophy with associated
      muscular facial pain treated with botulinum toxin.

PMID- 11323941
TI  - Gender variations in the social impact of oral health.
AB  - BACKGROUND: There is a growing interest in gender related health issues, however,
      there is little data concerning the relationships between oral health and gender
      other than on tooth loss. In particular, there is little information on
      differences in the social impact of oral health between men and women. AIM: The
      aim of this study was to identify gender variations in the social and
      psychological impacts of oral health. DESIGN: A random probability sample of
      1,865 adults (1,049 women and 816 men) took part in the study to determine how
      oral health "reduces" and "adds to" quality of life in a nation-wide survey.
      RESULTS: Women perceived oral health as having a greater impact than men on their
      quality of life in general, having a greater negative impact (p < 0.01) and a
      greater positive impact (p < 0.05). Specifically women perceived oral health as
      causing them more pain (p < 0.05), embarrassment (p < 0.05) and being detrimental
      to their finances (p < 0.05) compared to men. Women also more frequently
      perceived oral health as enhancing their life quality (p < 0.05), their moods (p
      < 0.05), their appearance (p < 0.01) and their general well being (p < 0.01) than
      men. CONCLUSION: There are gender variations in the social and psychological
      impacts of oral health. These findings may help in understanding gender
      differences in oral health needs and behaviour and have implications in assessing
      oral health needs.

PMID- 11323942
TI  - Red man syndrome during administration of prophylactic antibiotic against
      infective endocarditis.
AB  - Red man syndrome (RMS) is the occurrence flushing, pruritus, chest pain, muscle
      spasm or hypotension during vancomycin infusion. It usually happens as a result
      of rapid infusion of the drug but may also occur after slow administration. The
      frequency and severity of this phenomenon diminish with repeated administration
      of vancomycin. A case is presented whereby RMS occurred while prophylactic
      antibiotic against infective endocarditis was administered.

PMID- 11323943
TI  - Patient satisfaction in an emergency dental clinic.
AB  - OBJECTIVES: Attendance at emergency clinics may be accompanied by extensive
      waiting times and frustration and may not result in patients obtaining the
      treatment which they expected. The objective of the study was to ascertain
      patient satisfaction with the overall provision of day time emergency services in
      a university dental teaching hospital, for quality assurance purposes. METHODS:
      Patients (or persons accompanying child patients) attending the clinic, selected
      according to a sampling frame designed to identify approximately 10 per cent of
      attendees, completed a questionnaire. RESULTS: High levels of patient
      satisfaction were found; 17 of 24 questions scoring satisfaction on a scale 1-5
      had median scores of 5, six had median scores of 4 and one had a median score of
      3. The lower scores related mostly to patient facilities rather than treatment.
      CONCLUSIONS: Overall patient satisfaction with their dental A & E experience has
      been extremely positive, probably attributable to a well motivated staff using a
      team approach.

PMID- 11323944
TI  - A quiet wind of change.

PMID- 11323945
TI  - Herpesvirus-induced diseases: oral manifestations and current treatment options.
AB  - The dentist is often the first health professional to be contracted by patients
      who develop acute orofacial symptoms of viral conditions such as shingles
      (varicella zoster) or herpetic gingivostomatitis. The diagnosis, treatment, and
      management of virally induced oral diseases is a challenge inasmuch as their
      presentation is atypical and may be complicated by immunosuppression. However, an
      increasing body of knowledge regarding the manifestations of viral infections in
      immunocompromised patients and the advances achieved in antiviral drug therapy
      during the past several years should make the task less daunting for the dentist.
      In this paper, the natural history, typical and atypical oral manifestations,
      diagnosis, current treatment options, and advances in the prevention of common
      herpesvirus-induced diseases are reviewed, with particular attention to primary
      and recurrent varicella zoster virus and herpes simplex type 1 infections.

PMID- 11323946
TI  - Papillary lesions of the oral cavity: relationship to human papillomaviruses.
AB  - Human papillomaviruses are a group of genetically related organisms that infect
      stratified squamous epithelium. Unlike many other viruses that infect oral
      epithelium and induce lysis of the cells they penetrate, HPVs induce
      proliferative changes in these cells that result in both benign and malignant
      tumors. The common skin wart (verruca vulgaris) is induced by HPV 2 and 4.
      Genital warts (condylomas) and the common solitary oral papilloma are associated
      with HPV 6 and 11. Either HPV 13 or 32 causes focal epithelial hyperplasia. All
      of these wart-like lesions are benign growths of the stratified squamous lining
      of the oral cavity and lips and can be treated by surgical excision or laser
      ablation. HPV 16 and other less frequently encountered genotypes are associated
      with uterine cervix cancer in 95 percent to 98 percent of cases, and the evidence
      for a causal role is robust. There are emerging data that implicate HPV in
      certain subsets of oral cancer, particularly those that arise in the
      oropharynx/tonsillar region. Some instances of the various histologic subtypes
      subsumed under proliferative verrucous leukoplakia and verrucous carcinoma also
      harbor HPV.

PMID- 11323947
TI  - The bullous desquamative lesions of oral mucosa.
AB  - The most common of the bullous/desquamative diseases that affect the mouth
      include the erosive form of lichen planus, erythema multiforme, pemphigoid, and
      pemphigus. This overview looks at the clinical features and diagnosis of these
      diseases. In addition, treatment options are discussed.

PMID- 11323948
TI  - Xerostomia--clinical evaluation and treatment in general practice.
AB  - Xerostomia is a common symptom with various causes that, if ignored, can lead to
      serious oral consequences. Clinical evaluation of patients complaining of dry
      mouth must include some additional history and specific examination of the
      salivary glands, oral mucosa, and teeth. Additional evaluation may include
      consultation with the patient's physician, request for microbial culture, or
      labial salivary gland biopsy. No one form of treatment for patients with chronic
      xerostomia is sufficient, but comprehensive treatment is effective in improving
      patient oral comfort and function and preventing unnecessary loss of teeth. This
      treatment must include ongoing dental caries prevention and treatment, salivary
      flow stimulation, recognition and treatment of oral candidiasis, selective use of
      saliva substitutes, and possible changes in the patients' prescription and
      nonprescription drug use.

PMID- 11323949
TI  - Candidiasis: pathogenesis, clinical characteristics, and treatment.
AB  - Candida organisms live on the skin and mucous membranes of up to 75 percent of
      the population. They can live commensally without causing harm or can change to
      an aggressive form and invade tissue, causing both acute and chronic disease in
      the host. Oropharyngeal candidiasis manifests clinically as acute
      pseudomembranous, acute atrophic, chronic atrophic, chronic
      hypertrophic/hyperplastic, and angular cheilitis. Systemic infection leading to
      candidemia can be devastating and cause up to a 60 percent mortality rate in
      medical or post-surgical intensive care wards. Oral nystatin, clotrimazole, and
      fluconazole usually provide appropriate therapy; although resistance to
      medications is increasing, particularly in immunocompromised hosts.

PMID- 11323950
TI  - Focal, flat pigmentations of the oral mucosa: a clinical approach to the
      differential diagnosis.
AB  - The purpose of this article is to assist the clinician in establishing a clinical
      approach to the diagnosis of focal, flat pigmentations of the oral mucosa. These
      pigmentations include lesions that may be blue, purple, red, black, or brown. The
      etiopathogenesis may be variable and the pigment may originate from an exogenous
      (extrinsic) or endogenous (intrinsic) source. Exogenous pigmentations are of a
      traumatic or iatrogenic origin. Intrinsic pigmentations are either vascular or
      melanocytic. Clinical approaches include a thorough history and physical exam
      coupled with diascopy (blanchability), radiographs, and tissue examination
      (biopsies). An algorithm is presented to clarify the diagnostic approach. The
      diagnosis may vary from pathologic entities that require no treatment to others
      that may involve malignancies and their associated management. It is therefore
      extremely important that these lesions are identified and properly managed in an
      expeditious manner.

PMID- 11323951
TI  - Diet drugs and cardiac valvulopathy: a survey of dental patients.
AB  - The recent finding that several appetite suppressant drugs (fenfluramine and
      dexfenfluramine) were linked to cardiac valvular disease in a significant
      percentage of the population led to their voluntary withdrawal. The Centers for
      Disease Control and Prevention issued a series of recommendations in 1997 for
      evaluating dental patients who had taken these drugs. Since that time, several
      studies have further investigated the prevalence of valvular abnormalities. This
      information is crucial because of the problem of dentally associated bacterial
      endocarditis. This study surveyed more than 1,300 dental patients and determined
      the prevalence of patients taking these diet drugs and cardiac valvulopathy and
      the percentage of dental patients required to take antimicrobial endocarditis
      prophylaxis before "at risk" dental procedures. It remains important for dentists
      to query their patients for this information.

PMID- 11323952
TI  - Restoration of a modified solid abutment of the ITI dental implant system: one of
      the most unique systems in implant dentistry.
AB  - Although this system requires the use of some different impression techniques, it
      provides the dentist and technician a unique and simple method to restore a
      missing tooth with an implant-retained crown. The Straumann ITI impression coping
      and analog system allow the fabrication of a hybrid die for predictable results.

PMID- 11323953
TI  - Eliminating the job everyone hates to do.

PMID- 11323954
TI  - Dental lab technology in the digital age.
AB  - The "Information Age" is starting to have an impact on dental technology.
      Procera, Cerac and several other digital systems are commonly used by many
      technicians. Other systems are being developed and marketed. Computer Aided
      Design (CAD) can be used by dental technicians to create precise dental
      restorations. Solid modeling techniques can provide unique dental applications.

PMID- 11323955
TI  - Periodontists report dental implants are bringing smiles to patients' faces.

PMID- 11323957
TI  - Start the year off by communicating correctly with yourself!

PMID- 11323956
TI  - Wages? What do you get for what you pay?

PMID- 11323958
TI  - Be part of the team.

PMID- 11323959
TI  - Outstanding technicians must be recognized.

PMID- 11323960
TI  - [Stillbirth--what to do next? From the viewpoint of the mother and the pediatric
      nurse].

PMID- 11323961
TI  - [Organ transplantation--psychological effects].

PMID- 11323962
TI  - [Nursing theory of interventions in families of children with chronic diseases].

PMID- 11323963
TI  - [German, Austrian and Swiss nutrition groups publish new reference values for
      nutrition].

PMID- 11323964
TI  - [Pediatric nursing today--what it can accomplish, what it does accomplish].

PMID- 11323965
TI  - [Strained mother-child relationship].

PMID- 11323966
TI  - [Conservative therapy of childhood epilepsy].

PMID- 11323967
TI  - [The marketing of nursing--questionable experience].

PMID- 11323968
TI  - [Transition to motherhood--an Australian nursing study].

PMID- 11323969
TI  - [Crises and mistakes of adolescence].

PMID- 11323970
TI  - [Breast feeding--more than just nutrition].

PMID- 11323971
TI  - [Complete weekly nursing care at a university clinic. Experience and practice at
      the Stockholm Karolinska Hospital].

PMID- 11323972
TI  - [Pleasant bandages for infants and young children--pediatric home care].

PMID- 11323973
TI  - [Spectrum of the tasks of human genetics].

PMID- 11323974
TI  - [Medical care of the dying child--nursing problems in dealing with dying infants
      in neonatology].

PMID- 11323975
TI  - [Controversies about pre-implantation diagnosis from the viewpoint legislation in
      Germany. Comments of a neonatologist].

PMID- 11323976
TI  - [Human genetics--an unethical proposal?].

PMID- 11323977
TI  - Blood flow through an axisymmetric stenosis.
AB  - This paper studies a steady axisymmetric flow in a constricted rigid tube. A
      shear-thinning fluid modelling the deformation-dependent viscosity of the blood
      is proposed. The motion equation is written in vorticity-streamfunction
      formulation and is solved numerically by a finite difference scheme. The flow
      pattern with the distributions of pressure and shear stress at the wall are
      computed. The dependence of the flow on the dimensionless parameters has been
      investigated and differences from the Newtonian case are discussed.

PMID- 11323978
TI  - Fluid absorption study in ultra-high molecular weight polyethylene (UHMWPE)
      sterilized and unsterilized acetabular cups.
AB  - The weight gain due to fluid absorption was measured in gamma-sterilized,
      ethylene oxide (ETO) gas-sterilized, and unsterilized ultra-high molecular weight
      (UHMW) polyethylene acetabular cups. After about 2 months the total average fluid
      absorption gain of the polyethylene cups was: 1.76 +/- 0.45 mg (average +/-
      standard deviation) for the unsterilized polyethylene cups, 2.81 +/- 0.95 mg for
      the gamma-sterilized polyethylene cups and 1.51 +/- 0.34 for the ETO gas
      sterilized polyethylene cups. There was little difference in fluid absorption
      between the sterilized and unsterilized specimens. In particular, the gamma
      sterilized acetabular cups absorbed more than the ETO gas-sterilized and the
      unsterilized cups. However, the weight gain was higher in serum compared with
      that in water.

PMID- 11323979
TI  - Advanced textile composite ring for Ilizarov external fixator system.
AB  - The use of a radiolucent composite material permits easier and more accurate
      radiographic evaluation of the bone healing process, and results in a much
      lighter system. The finite element method (FEM) is employed to determine the
      worst possible in-service loading condition and the ring dimensions are modified
      accordingly. Half-ring prototypes are produced using two types of composite
      materials: knitted aramid fibre fabric reinforced epoxy and random short carbon
      (RSC) fibre reinforced epoxy. The in-plane compressive strength and axial
      stiffness of the complete frame are tested according to ASTM specifications. The
      performance is evaluated, and compared with an existing system in simulated in
      service conditions.

PMID- 11323980
TI  - Temperature and ageing condition effects on the characterization of acrylic bone
      cement.
AB  - This study investigates the effect of the environmental temperature and ageing
      condition on the characterization of acrylic bone cement. The tests were
      performed according to ISO 5833. The testing parameters were allowed to vary
      within the limits defined by the standard, in order to assess their effect on the
      results of the test. In certain cases the tests were also performed under
      conditions which the standard does not provide for but which are likely to occur
      clinically. This investigation showed that the cement behaviour may also change
      in the temperature range specified in the standard. Therefore, it is deemed
      appropriate to correlate the curing parameters of the bone cement to the
      environmental temperature, performing the test at different temperatures. In this
      way the effect of temperature on the duration of the phases in the cement curing
      could be assessed. The resultant graphical representation of the effect of
      temperature on the duration of the phases in cement curing has direct clinical
      relevance. Furthermore, this study showed that the ageing conditions of the
      mechanically tested specimens affected the results. Hence, it is deemed advisable
      to modify the ageing conditions of the specimens, fixing them closer to the in
      vivo conditions.

PMID- 11323981
TI  - Influence of simulator kinematics on the wear of metal-on-metal hip prostheses.
AB  - There is now considerable interest in metal-on-metal bearings for hip prostheses.
      Extremely low wear rates (0.1 mm3/10(6) cycles) have been reported in some
      simulator studies, while in vivo studies, although still very low, have shown
      wear rates of the order of 1 mm3/10(6) cycles. The aim of this study was to
      compare wear rates of metal-on-metal bearings in two hip simulators with
      different kinematic inputs. In the simulator with three independent input motions
      which produced an open elliptical wear path with a low level of eccentricity, the
      wear rates were very low as recorded previously in other simulators. In the
      simulator with two input motions which produced an open elliptical wear path with
      greater eccentricity the wear rate was at least ten times higher and closer to
      clinical values. The motion and kinematic conditions in the contact are critical
      determinants of wear in metal-on-metal bearings.

PMID- 11323982
TI  - A technique for measuring the compressive modulus of articular cartilage under
      physiological loading rates with preliminary results.

PMID- 11323983
TI  - An improved three-dimensional direct numerical modelling and thermal analysis of
      a female breast with tumour.
AB  - It is well known that malignant tumour tissue generally has higher metabolic and
      blood perfusion rates than most normal tissues. The authors aim to show that the
      tissue temperature profile within the breast and the surface temperature profile
      can be quantified to develop an expert system or diagnostic tool for breast
      cancer detection. The surface temperature and tissue temperature profiles are
      analysed for a three-dimensional numerical model of a normal breast and a breast
      with a tumour. Tumours of different sizes are placed at various locations. In the
      model, the tissue temperature profile is distorted at the tumour location and was
      found to compare well with in vivo tests. It was also found that as the tumour
      was moved to deeper locations its effect on surface temperature was lower. It was
      observed that small tumours in deeper regions do not have a significant isolated
      impact on the surface. The numerical results could also capture a shift in the
      position of the tumour. For tumours greater than 10 mm in the superficial regions
      and of significant size in deeper regions, it could be seen that the surface
      temperature distribution of the breast is directly related to the position and
      size of the tumour embedded in it. The feasibility of providing a diagnostic tool
      in conjunction with numerical modelling and high-resolution thermograms is also
      discussed.

PMID- 11323984
TI  - Suprapubic track pressure and force--deformation measurements in a (live) human
      subject and in animal models post-mortem.
AB  - Tests have been performed on animal models shortly post-mortem and on a healthy
      human subject in order to obtain estimates of the forces which act on suprapubic
      urinary catheters and similar devices and to develop an abdominal wall simulator.
      Such data and test methods are required for the systematic design of suprapubic
      devices because of the dual need to maintain the functionality of devices and to
      avoid excessive pressure on soft body tissue which could lead to ischaemia and in
      turn necrosis. In the post-mortem animal models, electrical excitation was
      applied to the abdominal wall in order to stimulate muscle activity. Two types of
      transducers were used: a soft membrane transducer (SMT) for pressure measurement
      and novel instrumented 'tongs' to determine indentation stiffness characteristics
      in the suprapubic track or artificial pathway created for a device. The SMT has
      been extensively used in the urethras and bladders of human subjects while the
      tongs were built specifically for these tests. Only the well-established SMT was
      used with the human subject; a peak pressure of 22 kPa was obtained. In the
      animal models the pressure profile given by the SMT had a peak whose position
      corresponded well with the estimated location of the rectus muscle measured on
      the fixed tissue section. The peak value was 5.5 kPa, comparable with values
      likely to cause necrosis if maintained for more than 1 day. Remarkably consistent
      indentation stiffness values were obtained with the instrumented tongs; all
      values were close to 0.45 N/mm (33 kPa/mm).

PMID- 11323985
TI  - Magnetic tracker calibration for an augmented reality system for therapy.
AB  - Magnetic trackers are widely used position/orientation measurement devices in
      interactive computer systems. These trackers output six-degree-of-freedom
      position and orientation of their receiver coordinates with respect to their
      transmitter coordinates. It is a potential solution for real-time
      position/orientation measurement in an augmented reality system for therapy
      (ART). However, an obstruction to be overcome is that a magnetic tracker is
      vulnerable to measurement inaccuracy caused by magnetic field distortions
      (including ferric and non-ferric distortions) when it is used in metallic
      environments. The purpose of this paper is to discuss calibration methods used to
      compensate distortions produced by metallic objects which are moving during the
      measurement procedure, but fixed with a receiver. Past work on the calibration of
      magnetic trackers has concentrated on static distortions, which are produced by
      stationary metallic objects in the environment. Compared with static distortions,
      in this paper a relatively dynamic situation is considered where the distortion
      is not constant with time. However, the location of the metallic objects is
      reflected in the outputs of the receiver so that the distortion can be
      compensated. This type of distortions, which is called 'quasi-static distortion'
      in this paper, is common in an ART. Compensation of quasi-static distortion is
      more complicated than that of static distortion and has not been mentioned in
      past publications. Some new compensation methods for quasi-static distortion will
      be introduced here. The results demonstrate that the methods are capable of
      significantly reducing quasi-static distortions.

PMID- 11323986
TI  - A five-station hip joint simulator.
AB  - A five-station hip joint wear simulator was designed and built which featured
      simplified motion and loading. An elliptical wear path was produced using
      approximately sinusoidal motion in the flexion/extension and internal/external
      rotation axes and the dynamic loading approximated to a square wave. Five 28 mm
      diameter zirconia femoral heads articulated against ultra-high molecular weight
      polyethylene acetabular cups in 25 per cent bovine serum for 5 x 10(6) cycles.
      Gravimetric wear measurement was used with moisture absorption compensation using
      a dynamically loaded soak control. With motion of physiological magnitude, the
      mean acetabular cup wear rate was 52.2 mm3/10(6) cycles which is comparable with
      a number of clinical studies.

PMID- 11323987
TI  - A comparative evaluation of dental luting cements by fracture toughness tests and
      fractography.
AB  - In recent years there has been a shift from traditional methods of investigating
      dental materials to a fracture mechanics approach. Fracture toughness (KIC) is an
      intrinsic material property which can be considered to be a measure of a
      material's resistance to crack propagation. Glass-ionomer cements are
      biocompatible and bioactive dental restorative materials, but they suffer from
      poor fracture toughness and are extremely susceptible to dehydration. The main
      objective of this study was to evaluate the fracture toughness of three types of
      commercially available dental cements (polyacid-modified composite resin, resin
      modified and conventional glass ionomer) using a short-rod chevron-notch test and
      to investigate and interpret the results by means of fractography using scanning
      electron microscopy. Ten specimens of each cement were fabricated according to
      manufacturers' instructions, coated in varnish, and stored at ambient laboratory
      humidity, 100 per cent relative humidity, or in water at 37 degrees C for 7 days
      prior to preparation for testing. Results indicated that significant differences
      existed between each group of materials and that the fracture toughness ranged
      from 0.27 to 0.72 MN/m3/2. It was concluded that the resin-modified glass-ionomer
      cement demonstrated the highest resistance to crack propagation. Fractographs
      clearly showed areas of stable and unstable crack growth along the fractured
      surfaces for the three materials examined.

PMID- 11323988
TI  - In vitro testing of the primary stability of the VerSys enhanced taper stem: a
      comparative study in intact and intraoperatively cracked femora.
AB  - The Zimmer VerSys enhanced taper uncemented stem was tested in vitro for primary
      stability. Six stems were implanted in six composite femora. Three femora were
      unintentionally damaged by cracking of the bone during stem insertion and press
      fit. A previously validated protocol was used to load the specimens cyclically
      and to record locally the rotational and axial bone/implant relative motions in
      terms of elastic motion and permanent migration. For the undamaged femora, the
      VerSys stem showed excellent primary stability, in terms of both elastic motions
      (less than 9 microns) and permanent migrations (less than 6 microns), and in both
      axial and rotational directions, comparing favorably with the literature.
      Intraoperatively-induced proximal cracks did influence the primary stability of
      the stem in terms of permanent migration. As cracks may easily be produced in the
      diaphyseal canal during insertion of cementless stems, which rely for primary
      stability on conical fitting into the canal, great care must be taken in
      preparation of the canal and insertion of the stem.

PMID- 11323989
TI  - A comparison between automatically generated linear and parabolic tetrahedra when
      used to mesh a human femur.
AB  - Finite element models of bone segments generated from computed tomography data
      using automatic mesh generation algorithms are becoming common not only in
      research but also in clinical applications such as computer aided orthopaedic
      surgery. Especially in the case of the latter application, the models cannot be
      verified against an experimental measurement, therefore their inherent accuracy
      should be well known before drawing conclusions based on the calculated results.
      This study was carried out to assess the performance of tetrahedral solid finite
      elements with linear and quadratic displacement functions when they are used to
      mesh the human femur in conjunction with automatic mesh generator methods. Ten
      node quadratic tetrahedra (T10) having parabolic displacement functions were
      compared with four-node linear tetrahedron elements (T4) on the basis of accuracy
      and central processing unit (CPU) time. From the analyses of 11 finite element
      meshes, it was concluded that linear tetrahedral elements should be avoided and
      quadratic tetrahedral elements ought to be chosen for the purposes of finite
      element analysis of the human femur. When incremental loading and iterative
      solution is necessary, the coarsest possible T10 mesh compatible with accuracy is
      needed to minimize computer capacity and CPU time.

PMID- 11323990
TI  - The effect of kinematic conditions on the wear of ultra-high molecular weight
      polyethylene (UHMWPE) in orthopaedic bearing applications.
AB  - It is known that wear mechanisms differ between the ultra-high molecular weight
      polyethylene (UHMWPE) components of total hip replacement (THR) and total knee
      replacement (TKR). The difference in relative contact position or 'kinematic
      conditions of contact' between the metal and polymer components is thought to
      contribute to the contrast in observed wear mechanisms. A reciprocating wear
      tester was used to evaluate three basic kinematic contact conditions: sliding, in
      which the relative contact position on the polymer remains stationary; gliding,
      where the contact position on the polymer reciprocates; and rolling, where the
      contact position on the polymer varies and the relative velocities of both
      components are equal. All static load tests used cast Co-Cr alloy and irradiated
      Chirulen UHMWPE in a 37 degrees C environment lubricated with bovine serum
      albumin. UHMWPE test sample wear was measured gravimetrically at intervals of
      600,000 cycles. The results indicated a difference in wear factor (volume lost
      due to wear per unit load per unit sliding distance) between the three groups
      with varying relative motion. The study indicates that screening tests which
      evaluate wear properties of new materials for total joint replacement should
      reflect the different kinematic contact conditions.

PMID- 11323991
TI  - Patterns of attendance and treatment at an emergency dental clinic: a three year
      follow-up.
AB  - OBJECTIVES: Patterns of attendance at the Dublin Dental Hospital's Accident and
      Emergency Clinic in 1996 were compared with figures from 1993 to look for
      changes, especially in the light of changing provision of public funding for
      dental treatment for medical card holders and dependants. METHODS: An audit of
      patient clinical records for one month in 1996 was compared to previously
      published data relating to 1993. RESULTS: While patient numbers were similar in
      the two time periods (718 in 1993 versus 708 in 1996), the proportion of
      attendances by medical card holders or their dependants dropped from 48 per cent
      to 36 per cent. The proportion of non urgent treatments had also dropped over the
      three years. CONCLUSIONS: Changes in the provision of publicly funded dental
      treatment for medical card holders and dependants has reduced the proportion of
      such patients attending the clinic. However, their places have been taken by
      other patients.

PMID- 11323992
TI  - Ellis-van Creveld (EVC) syndrome. A case report.

PMID- 11323993
TI  - Working with a dental hygienist in Ireland.
AB  - The category of dental hygienist was introduced in Ireland in 1990 in accordance
      with the scheme made by The Dental Council [An Chomhairle Fiacloireachta] under
      the provision of Part VII of the Dentists Act 1985. This paper sets out and
      discusses the instructions of the Dental Council for employing/supervising
      dentists and registered dental hygienists as they apply at the time of writing.
      The current status and possible future developments are also considered in
      relation to the delivery of patient care by the dental team.

PMID- 11323994
TI  - Laboratory fabrication of a single crown on the non-modified solid abutment of
      the ITI Dental Implant System.
AB  - Fabricating a crown and bridge for the ITI Solid Abutment can be easier than
      conventional units if a few changes in technique are accomplished. Burnout times
      and temperatures are extremely important. Devesting and finishing the casting
      must be carried out following the manufactures instructions.

PMID- 11323995
TI  - Dental implants. Be part of the team.

PMID- 11323996
TI  - Twelve communication keys to keeping good technicians.

PMID- 11323997
TI  - Increasing the esthetics, production and profit of fabricating ceramic
      restorations with an alternative build-up technique.
AB  - The purpose of this article is to demonstrate the advantages and benefits of
      utilizing The Dry Powder Technique during the fabrication of ceramic
      restorations. This article explains how to create esthetically superior
      restorations using an unlimited number of porcelain powders while conserving time
      and materials. By utilizing dry powder storage containers, kolinsky sable
      brushes, capillary attraction and multiple oven firing procedures, a ceramist may
      control grain size distribution, color and contour with a minimum of effort and
      maximum of results.

PMID- 11323998
TI  - Comparative evaluation of calcium hydroxide and zinc oxide eugenol as root canal
      filling materials for primary molars: a clinical and radiographic study.
AB  - Calcium hydroxide, a material widely used for the treatment of permanent teeth
      has not been used frequently for pulpectomy in primary teeth. A comparative
      evaluation of calcium hydroxide and zinc oxide eugenol used as root canal filling
      materials in primary molars is presented.

PMID- 11323999
TI  - Prevalence of dental disease amongst 5-6 and 12-13 year old school children of
      Puttur municipality, Karnataka State-India.
AB  - A survey was conducted among 5-6 and 12-13 years old school children of Puttur
      municipality, Karnataka State, India, to assess the prevalence of dental caries,
      malocclusion and dental calculus. A sample size of 200 subjects was taken for
      each age group and cluster-sampling method was used to select those schools which
      were to be included in the sample frame. Data collection was done using the Basic
      Oral Health Survey (WHO) form. The deciduous dentition alone was considered for 5
      6 year old subjects while the permanent dentition alone was considered for those
      aged 12-13 years. A total of 427 subjects from 7 schools were studied. Results
      indicated that 81.25% of 5-6 year old subjects had dental caries (mean dmft =
      4.86 +/- 4.16 S.D.) as compared to 59.6% of 12-13 year old (mean DMFT = 1.87 +/-
      2.01 S.D.). The prevalence of malocclusion was 1.79% and 36.95% among those aged
      5-6 year and 12-13 year, respectively. None of the 5-6 years old subjects had
      calculus on their teeth while 47.78% of 12-13 year old subjects exhibited the
      presence of dental calculus. Overall the prevalence of dental caries was found to
      be significantly higher among 5-6 year old subjects compared to 12-13 year old
      subjects. The prevalence of malocclusion and dental calculus was significantly
      higher among 12-13 year old subjects compared to 5-6 year old subjects.

PMID- 11324000
TI  - Molariform supernumerary tooth--a case report.
AB  - The occurrence of a single supernumerary tooth in the upper canine region a rare
      condition is reported. The crown resembles a molar tooth, thus suggesting a
      molariform supernumerary tooth.

PMID- 11324001
TI  - Non-specific inflammatory gingival enlargement--a case report.
AB  - An unusual case of unilateral idiopathic gingival hyperplasia in a 6 year old
      child is reported and its management discussed.

PMID- 11324002
TI  - Maxillary expansion--an interceptive modality in mixed dentition.
AB  - Maxillary expansion is a very useful procedure for arch length augmentation,
      posterior crossbite treatment and removing cross arch interferences. Removable
      appliances are in the realm of a pedodontist and general dentist. However, one
      should be aware of the problems arising at an early age of the child, should be
      able to properly diagnose the condition and if required, a timely referral to a
      specialist is also expected.

PMID- 11324003
TI  - Assessment of dental treatment required and analysis of cost in the management of
      dental caries among semiurban primary school children of Kerala.
AB  - The study was carried out with the purpose of assessing the dental treatment
      requirement and analysis of cost in the management of dental caries among primary
      school children of Kerala. The sample consisted of 750 primary school children
      and their parents. 68.5% children were affected with dental caries. Decayed teeth
      accounted for the largest component. One surface restorations were the most
      frequent type of treatment required followed by extractions, pit and fissure
      sealants and pulp therapy. The treatment cost increased in direct proportion to
      the number of teeth involved. The average cost incurred for various dental
      treatment varied from Rs. 50 (consultation) to Rs. 300 (for filling and
      extraction) depending on the nature of treatment. Only 1/3rd of children
      requiring immediate dental treatment had approached for any form of dental
      consultation. The study also revealed that all the children who had approached
      the dentist for consultation and treatment had only done for temporary relief in
      relation to emergency management.

PMID- 11324004
TI  - Dentigerous cyst with an impacted canine in an unusual position-a case report.
AB  - A dentigerous cyst is a type of an odontogenic cyst associated with the crown of
      an impacted, embedded or unerupted tooth. In this article, we report a case of
      dentigerous cyst with an impacted canine in an unusual position which was
      surgically removed.

PMID- 11324005
TI  - Trend of dental caries in children of Chandigarh over the last sixteen years.
AB  - The trend of dental caries in Chandigarh school children over a sixteen year
      period, studied by almost the same authors and using the same recording criteria
      of WHO reveals a continuous decline in 12 and 15 year children but a slight
      increase in the dental caries status of 5-6 year children. In 1977, the mean DMFT
      of 12 and 15 year children was 3.88 and 4.74 respectively. In 1985, it decreased
      to 1.38 in 15 year olds (12 year children not recorded) and in 1993 it marginally
      decreased to 1.12 +/- 1.35, much lower than the figure of 3.88 in 1977. In 5-6
      year children, mean dmft/dmfs of 2.69 +/- 1.45 and 6.06 +/- 9.77 was found to be
      slightly higher as compared to the earlier caries prevalence figures (deft + DMFT
      2.6 in 1977 and 2.26 in 1985).

PMID- 11324006
TI  - Can mouthwash weaken resins?

PMID- 11324007
TI  - ADA survey reveals decreased enrollment in dental laboratory technology programs.

PMID- 11324008
TI  - Delegation in the dental lab. What is it and why do it?

PMID- 11324009
TI  - Law ups ante on nitrous oxide possession and distribution.

PMID- 11324010
TI  - Working with the media is important.

PMID- 11324011
TI  - Is your lab working as a team? Teamwork leads to a happy productive lab.

PMID- 11324012
TI  - Restructuring to meet the future challenges.

PMID- 11324013
TI  - Design and fabrication technique for metal palates in maxillary complete
      dentures.
AB  - Polymethyl methacrylate exhibits excellent physical properties. Unfortunately,
      complete dentures fabricated from this material may still fracture. Maxillary
      complete dentures opposing natural dentition may have a tendency to develop
      recurrent midline fractures due to multiple reasons. A potential method of
      preventing this fracture is metal reinforcement of the palatal portion of the
      prosthesis. A technique will be presented describing a sequence that incorporates
      predictable design, fabrication and finishing of a metal palate for a maxillary
      complete denture.

PMID- 11324014
TI  - Chronicling the birth of a discipline.

PMID- 11324015
TI  - Using RNAi to investigate orthologous homeotic gene function during development
      of distantly related insects.
AB  - Gene product distribution is often used to infer developmental similarities and
      differences in animals with evolutionarily diverse body plans. However, to
      address commonalties of developmental mechanisms, what is really needed is a
      method to assess and compare gene function in divergent organisms. This requires
      mutations eliminating gene function. Such mutations are often difficult to
      obtain, even in organisms amenable to genetic analysis. To address this issue we
      have investigated the use of double-stranded RNA interference to phenocopy null
      mutations. We show that RNA interference can be used to phenocopy mutations of
      the Deformed orthologues in Drosophila and Tribolium. We discuss the possible use
      of this technique for comparisons of developmental mechanisms in organisms with
      differing ontogenies.

PMID- 11324017
TI  - The stability of thoracic segmentation in trilobites: a case study in
      developmental and ecological constraints.
AB  - The decline in origination rate of new metazoan body plans following the Cambrian
      radiation has been suggested to reflect developmental canalization in derived
      taxa, limiting their ability to evolve forms with radically different
      morphotypes. Segmentation is a fundamental aspect of arthropod body plan, and
      here we show that a derived trilobite that secondarily converged on a morphotype
      characteristic of basal members of the clade also reverted to a pattern of
      segmental variability common among basal trilobites. Hence a secular trend in
      loss of variability of the trilobite thorax was not due to the evolution of an
      inviolable developmental constraint. This result challenges the notion of
      developmental canalization in phylogenetically derived taxa. Rather, early
      variability in trilobites may be the result of ecological factors that promoted
      segment-rich thoracic morphotypes during Cambrian time.

PMID- 11324016
TI  - Ancient origins of axial patterning genes: Hox genes and ParaHox genes in the
      Cnidaria.
AB  - Among the bilaterally symmetrical, triploblastic animals (the Bilateria), a
      conserved set of developmental regulatory genes are known to function in
      patterning the anterior-posterior (AP) axis. This set includes the well-studied
      Hox cluster genes, and the recently described genes of the ParaHox cluster, which
      is believed to be the evolutionary sister of the Hox cluster (Brooke et al.
      1998). The conserved role of these axial patterning genes in animals as diverse
      as frogs and flies is believed to reflect an underlying homology (i.e., all
      bilaterians derive from a common ancestor which possessed an AP axis and the
      developmental mechanisms responsible for patterning the axis). However, the
      origin and early evolution of Hox genes and ParaHox genes remain obscure.
      Repeated attempts have been made to reconstruct the early evolution of Hox genes
      by analyzing data from the triphoblastic animals, the Bilateria (Schubert et al.
      1993; Zhang and Nei 1996). A more precise dating of Hox origins has been elusive
      due to a lack of sufficient information from outgroup taxa such as the phylum
      Cnidaria (corals, hydras, jellyfishes, and sea anemones). In combination with
      outgroup taxa, another potential source of information about Hox origins is
      outgroup genes (e.g., the genes of the ParaHox cluster). In this article, we
      present cDNA sequences of two Hox-like genes (anthox2 and anthox6) from the sea
      anemone, Nematostella vectensis. Phylogenetic analysis indicates that anthox2 (=
      Cnox2) is homologous to the GSX class of ParaHox genes, and anthox6 is homologous
      to the anterior class of Hox genes. Therefore, the origin of Hox genes and
      ParaHox genes occurred prior to the evolutionary split between the Cnidaria and
      the Bilateria and predated the evolution of the anterior-posterior axis of
      bilaterian animals. Our analysis also suggests that the central Hox class was
      invented in the bilaterian lineage, subsequent to their split from the Cnidaria.

PMID- 11324018
TI  - From egg to adult to larva.

PMID- 11324019
TI  - Vertebral development and amphibian evolution.
AB  - Amphibians provide an unparalleled opportunity to integrate studies of
      development and evolution through the investigation of the fossil record of
      larval stages. The pattern of vertebral development in modern frogs strongly
      resembles that of Paleozoic labyrinthodonts in the great delay in the
      ossification of the vertebrae, with the centra forming much later than the neural
      arches. Slow ossification of the trunk vertebrae in frogs and the absence of
      ossification in the tail facilitate the rapid loss of the tail during
      metamorphosis, and may reflect retention of the pattern in their specific
      Paleozoic ancestors. Salamanders and caecilians ossify their centra at a much
      earlier stage than frogs, which resembles the condition in Paleozoic
      lepospondyls. The clearly distinct patterns and rates of vertebral development
      may indicate phylogenetic separation between the ultimate ancestors of frogs and
      those of salamanders and caecilians within the early radiation of ancestral
      tetrapods. This divergence may date from the Lower Carboniferous. Comparison with
      the molecular regulation of vertebral development described in modern mammals and
      birds suggests that the rapid chondrification of the centra in salamanders
      relative to that of frogs may result from the earlier migration of sclerotomal
      cells expressing Pax1 to the area surrounding the notochord.

PMID- 11324020
TI  - Variations in anuran embryogenesis: yolk-rich embryos of Hyperolius puncticulatus
      (Hyperoliidae).
AB  - Anuran development is usually described using model species, most notably Xenopus
      laevis and Rana pipiens. We describe the development of the East African Reed
      Frog, Hyperolius puncticulatus, a species displaying development that is highly
      divergent from the "classic" anuran developmental pattern. Although having small
      eggs, the eggs of H. puncticulatus are characterized by a large amount of yolk,
      and embryonic development is reminiscent of species with large eggs. The eggs are
      teleolecithal and the cleavage is holoblastic, with a "pseudo-meroblastic"
      pattern. Gastrulation proceeds primarily at the dorsal lip and is characterized
      by reduced embryonic cavities. Gastrulation ends with a thickened "embryonic
      mantle" that sits upon a large yolk mass and forms most of the tissues of the
      embryo. The embryonic axis curves across the yolk mass, instead of the typical
      lengthening of anuran embryos. The tadpole hatches with a large ventral yolk mass
      which is gradually absorbed. We hypothesize about the developmental mechanisms
      that underlie this unusual development, based on comparisons with other anuran
      and fish species. We suggest that this type of development is not unique to this
      species, but can be found in many species of different anuran taxonomic groups.
      Comparing the development of H. puncticulatus and similar species to what is
      known about the development of model species, such as X. laevis, shows us the
      variation in early anuran embryogenesis. Knowing the existing diversity is a
      prerequisite to understanding the evolution of early anuran development and the
      changes in patterning mechanisms in different lineages.

PMID- 11324021
TI  - Some problems with typological thinking in evolution and development.

PMID- 11324022
TI  - Variable segment number in centipedes: population genetics meets evolutionary
      developmental biology.
AB  - The case studies of population genetics focus on intraspecific variation, but
      most cases--at least where the variation is polymorphic--deal with characters
      that are not directly linked to organismic structure or ontogeny. Conversely, the
      case studies of evolutionary developmental biology focus directly on
      structure/ontogeny, but usually involve only interspecific comparisons. To
      integrate these complementary approaches, it is desirable to have a model system
      that permits study of intraspecific variation in development, using a character
      whose genetic basis either is already known or can be elucidated. Segment number
      in geophilomorph centipedes is proposed as a possible model system of this kind.
      Segment number is variable in natural populations of geophilomorphs, while in the
      other centipede orders it is fixed, either completely (scutigeromorphs,
      lithobiomorphs), or at least within species (scolopendromorphs). Statistical
      analysis of data on the extent of variation in different geophilomorph species
      suggests that segment number may be of selective importance, rather than the
      variation being merely an inevitable consequence of the difficulty of achieving a
      high degree of repeatability when there is a large number of segments.

PMID- 11324023
TI  - Convergence and the interplay of evolution and development.

PMID- 11324024
TI  - Clinicopathologic correlation quiz: solitary gingival exophytic growths.

PMID- 11324025
TI  - Student and faculty perceptions in the assessment of amalgam restorations.
AB  - The purpose of this in-vitro study was to compare the assessment of amalgam
      restorations made by dental students and faculty members. Extracted human teeth
      which contained old amalgam restorations were mounted in dental stone and labeled
      one through 25. All evaluators were instructed the restorations were those of a
      35-year-old patient with no clinical symptoms. The restorations were examined by
      57 dental students and 10 dental instructors. Each examiner was asked to accept
      the restorations or replace the restorations with accompanying reason(s).
      Approximately one year after the first assessment, the blocks were randomly
      relabeled and all examiners reevaluated the amalgam restorations. the mean number
      of replacements, reasons for replacement, and kappa values were calculated for
      this study. A total of 1,675 decisions to replace or not to replace were
      obtained. There were a total of 2,784 reasons for replacement made by the
      students and 410 total decisions made by the dental faculty at the initial and
      final assessments. The study showed that dental faculty were more conservative in
      their treatment decisions. Also, the intraexaminer scores (kappa values) showed
      lower reproducibility among the dental students.

PMID- 11324026
TI  - Axial variation in the three-spine stickleback: genetic and environmental
      factors.
AB  - Subtle differences in the pattern of arrangement of types of vertebrae and
      associated median skeletal structures between a benthic and limnetic species pair
      of three-spine stickleback from Paxton Lake, British Columbia, are typical of
      those found throughout the range of the Gasterosteus aculeatus species complex.
      We established laboratory colonies from just three individuals of each species,
      and studied the effect of three generations of inbreeding on axial morphology.
      There was sufficient divergence in the location of individual elements between
      families to regenerate close to the entire range of axial diversity seen in
      threespine sticklebacks worldwide. Analysis of the patterns of variance and
      covariance between the axial locations of elements provides evidence for the
      action of both meristic and homeotic processes in the generation of morphological
      divergence within each species. Hybrid sticklebacks produced by the cross of
      limnetic and benthic parents tend to have intermediate morphologies, with
      dominance of either parental type evident for some elements. Effects of
      temperature and salinity were found to be small in direct comparison with between
      family effects, and varied according to genetic background. These results
      demonstrate that considerable genetic variation for axial morphology is
      maintained in natural populations of three-spine stickleback, and that
      differences between populations may be brought about rapidly by changes in
      frequency of alleles that have coordinated effects along the body axis.

PMID- 11324027
TI  - Hereditary stability and variation in evolution and development.
AB  - Evolution and development are both lineage processes but are often conceptualized
      as occurring by different and mutually exclusive mechanisms. It is conventionally
      asserted that evolution occurs via the random generation of diversity and the
      subsequent survival of those that pass selection. On the other hand, development
      is too often presented as proceeding via the unfolding of a deterministic program
      encoded in the DNA sequence. In biology, universal generalizations are rare and
      dogmas are often wrong for particular cases. Deterministic mechanisms contribute
      some of the new DNA sequences that subsequently become substrates for natural
      selection. Conversely, stochastic and selective mechanisms are intrinsic to
      development, and also to maintenance of the immune, and possibly, nervous
      systems. Cancer appears to be another process that straddles distinctions between
      evolutionary and developmental modes of hereditary change and stabilization. DNA
      sequence changes are an essential feature of many cancers, but there are also
      aspects of the disease similar to developmental lineage gone awry. The literature
      suggests that the cellular changes that give rise to cancer occur by mechanisms
      commonly associated with both evolutionary and developmental lineage pathways.

PMID- 11324028
TI  - Brief review of the stylophoran debate.
AB  - The "calcichordate" theory interprets an extinct group of calcite-plated
      invertebrates, the stylophorans, as chordates. In this theory, comute
      stylophorans are interpreted as stem chordates, whereas mitrate stylophorans are
      primitive members of the acraniates, tunicates, and craniates. However, this
      theory discounts major synapomorphies between comutes and mitrates. These groups
      constitute a natural, monophyletic group which is here argued to lie within the
      echinoderm radiation. The "calcichordate" theory is, therefore, rejected because
      it relies on assumption-driven hypotheses of character transformation which are
      supported by ambiguous, poor, or missing fossil evidence. Stylophorans may lie at
      the base of the echinoderm clade and primitively lack pentameral symmetry,
      therefore casting light on the near-ancestral body organization of the phylum.

PMID- 11324029
TI  - Synthesizing evolution, bird by bird.

PMID- 11324030
TI  - Segments, limbs, homology, and co-option.

PMID- 11324031
TI  - Chelicerate Hox genes and the homology of arthropod segments.
AB  - Genes of the homeotic complex (HOM-C) in insects and vertebrates are required for
      the specification of segments along the antero-posterior axis. Multiple
      paralogues of the Hox genes in the horseshoe crab Limulus poliphemus have been
      used as evidence for HOM-C duplications in the Chelicerata. We addressed this
      possibility through a limited PCR survey to sample the homeoboxes of two spider
      species, Steatoda triangulosa and Achaearanea tepidariorum. The survey did not
      provide evidence for multiple Hox clusters although we have found apparent
      duplicate copies of proboscipedia (pb) and Deformed (Dfd). In addition, we have
      cloned larger cDNA fragments of pb, zerknullt (zen/Hox3) and Dfd. These fragments
      allowed the determination of mRNA distribution by in situ hybridization. Our
      results are similar to the previously published expression patterns of Hox genes
      from another spider and an oribatid mite. Previous studies compared spider/mite
      Hox gene expression patterns with those of insects and argued for a pattern of
      segmental homology based on the assumption that the co-linear anterior boundaries
      of the Hox domains can be used as markers. To test this assumption we performed a
      comparative analysis of the expression patterns for UBX/ABD-A in chelicerates,
      myriapods, crustaceans, and insects. We conclude that the anterior boundary can
      be and is changed considerably during arthropod evolution and, therefore, Hox
      expression patterns should not be used as the sole criterion for identifying
      homology in different classes of arthropods.

PMID- 11324032
TI  - Developmental constraints on the mode of reproduction in the facultatively
      parthenogenetic cockroach Nauphoeta cinerea.
AB  - Considerable work in evolutionary biology has focused on the question of why sex
      persists. Both advantages to sex and constraints limiting a return to asexual
      reproduction are hypothesized to maintain sex once it evolves. Developmental
      constraints would limit asexual reproduction from a sexual species if it were
      difficult for females to switch from making eggs that do not develop without
      fertilization to making zygotes that are capable of developing in the absence of
      fertilization. Nauphoeta cinerea is an ovoviviparous cockroach in which some
      females are capable of switching from a sexual mode of reproduction to an asexual
      mode when isolated from males. Yet, while facultative parthenogenesis can occur
      in individuals, few females make the switch. Thus, this cockroach provides an
      ideal system for examining the potential role of developmental constraints in
      maintaining sex. Here we compare the cytogenetics and embryonic development of
      sexual and parthenogenetic offspring in N. cinerea. We find that deviations from
      normal ploidy levels are associated with abnormal development. All viable N.
      cinerea embryos exhibit typically hemimetabolous insect embryogenesis. Although
      there is no variation among embryos in development within a sexually produced
      clutch, we see extreme variation in asexually derived clutches. These results
      suggest that developmental constraints limit the success of asexual reproduction
      in this facultatively parthenogenetic cockroach. Our data further suggest that
      the specific constraint occurs in the switch from a meiotic mode of reproduction
      requiring fertilization to diploid zygotes that develop in the absence of
      fertilization.

PMID- 11324033
TI  - Affidavit of merit/tort reform statute.

PMID- 11324034
TI  - Be cautious about collection actions.

PMID- 11324035
TI  - Remembering Dr. John G. Nolen. A giant in Michigan dentistry.

PMID- 11324036
TI  - Antibiotic resistance and maxillofacial pathogens: emerging treatment issues.
AB  - The practice of using antibiotics to treat and control microbial infections is a
      little more than 50 years old. Widespread administration of multiple classes of
      antibiotics over the years has had the unfortunate secondary effect of inducing
      the emergence of an increasing array of drug-resistant microbial strains. This
      article will discuss the evolution of certain forms of antibiotic resistance, as
      well as the mechanisms by which bacteria render numerous antimicrobials
      ineffective. Special emphasis is placed on emerging issues relating to organisms
      making up portions of the normal oral microflora.

PMID- 11324037
TI  - Dental water line safety. What the dental practitioner should know.

PMID- 11324038
TI  - Dentistry in ancient mesopotamia.
AB  - Sumer, an empire in ancient Mesopotamia (southern Iraq), is well known as the
      cradle of our modern civilization and the home of biblical Abraham. An analysis
      of skeletal remains from cemeteries at the ancient cities of Ur and Kish (circa
      2000 B.C.), show a genetically homogeneous, diseased, and short-lived population.
      These ancient Mesopotamians suffered severe dental attrition (95 percent),
      periodontal disease (42 percent), and caries (2 percent). Many oral congenital
      and neoplastic lesions were noted. During this period, the "local dentists" knew
      only a few modern dental techniques. Skeletal (dental) evidence indicates that
      the population suffered from chronic malnutrition. Malnutrition was probably
      caused by famine, which is substantiated in historic cuneiform and biblical
      writings, geologic strata samples, and analysis of skeletal and forensic dental
      pathology. These people had modern dentition but relatively poor dental health.
      The population's lack of malocclusions, caries, and TMJ problems appear to be due
      to flat plane occlusion.

PMID- 11324039
TI  - Dental patients' attitudes toward making treatment decisions.

PMID- 11324040
TI  - The board of registration in dentistry. How to keep your dental practice out of
      trouble.

PMID- 11324041
TI  - Tufts man of the century, Dr. J. Murray Gavel.

PMID- 11324042
TI  - Oral midazolam syrup for sedation in pediatric dentistry.

PMID- 11324043
TI  - Missing the diagnosis of oral cancer: responsibility and liability.

PMID- 11324044
TI  - Fibrous dysplasia of the mandible. A clinico-pathologic presentation.

PMID- 11324045
TI  - Where to put a practice: factors to consider.
AB  - The temple of the Oracle at Delphi has "Know Thyself" engraved above it. Using
      modern demographic and psychographic research, it is both possible and practical
      to "know thy practice site" so that this important and risk-filled decision can
      be made rationally.

PMID- 11324046
TI  - OSHA 2000: a review of compliance issues.
AB  - The California Occupational Safety and Health Administration is responsible for
      enforcing worker safety regulations in the state of California. The infection
      control regulation, while the best known to dentists, is only one of many that
      affect every dental practice. The past two years have brought significant changes
      to Cal/OSHA rules. This paper reviews some of the current regulations that apply
      to dental offices.

PMID- 11324047
TI  - Women's oral health issues.
AB  - Hormonal fluctuations affect more than a woman's reproductive system. They have a
      surprisingly strong influence on the oral cavity. Puberty, menses, pregnancy, and
      menopause all influence women's oral health and the way in which a dentist should
      approach their treatment. This paper will review aspects of a woman's life when
      hormonal fluctuations may affect oral tissues.

PMID- 11324048
TI  - Soft tissue surgery in the oral and maxillofacial region.
AB  - The practice of dentistry is most often perceived as the treatment of the hard
      tissues of the oral region, specifically the teeth and jaws. However, there are
      many disorders and conditions involving surgical treatment of the soft tissues
      that extend to the adjacent and associated structures of the oral and
      maxillofacial surgery region.

PMID- 11324049
TI  - Oral health in America: a report of the Surgeon General.
AB  - The U.S. surgeon general released this year the nation's first official report on
      oral health. This document elaborates on the meaning of oral health and explains
      why oral health is essential to general health and well-being. We have reprinted
      here an abridged version of the report's Executive Summary. The full report can
      be accessed at.

PMID- 11324050
TI  - Effect of pressurized atmosphere on void size and quantity in dental stone and
      fine-grained phosphate-bonded investment.
AB  - This study investigated the effect of pressurized atmosphere on the size and
      number of voids in dental stones and investments. Control specimens of casts and
      invested patterns were bench set. Experimental specimens of casts and invested
      patterns were allowed to set under pressure. The specimens were then sectioned
      and voids counted and measured to establish a mean. Increased atmospheric
      pressure reduced the size and number of voids. This method produces improved cast
      surfaces and fewer, smaller voids in investments. Technicians are continuously
      searching for ways to improve the quality of their products. One method is
      placing dental casts and dental investments under increased atmospheric pressure
      while setting. Several pressure vessels are available for this purpose.

PMID- 11324051
TI  - Creating esthetic composite restorations: Part II, Crown fabrication.
AB  - The purpose of the article is to describe a fabrication technique to assist
      dental technicians to create an esthetic, indirect, high strength composite crown
      with fiber reinforcement. After the teeth have been prepared and the models
      completed the technician can begin the fabrication process. A fiber coping is
      fabricated on a separate transfer die. Translucent dentin is selected to reduce
      opacity and enhance the blend with the remaining dentition. High chroma dentin
      modifiers can then be place into the fossa, cervical, and interproximal areas to
      replicate dentin seen in natural dentition. Different incisal materials can then
      be layered into the build-up to regulate the value of the restoration. Special
      effects such as hypocalcification are placed internally to mimic naturally
      occurring esthetics. Realistic anatomy is created using a small tipped instrument
      directly into the final layer of uncured translucent blue enamel material.
      Fissure characterization is placed in the restoration to match existing
      dentition. Fit and margins are verified on separate dies to minimize
      discrepancies. Path of insertion and proximal contacts are established on a solid
      model to minimize chairside adjustments.

PMID- 11324052
TI  - Three unit metal-free inlay bridge.

PMID- 11324053
TI  - A look at alternatives in dental technology education programs.

PMID- 11324054
TI  - The little-known history of dental fillings; crown and bridge.

PMID- 11324055
TI  - Two new laws affect Arizona's dental community.

PMID- 11324057
TI  - Oral pathology quiz #28. Case 1. Ameloblastoma.

PMID- 11324056
TI  - Global antibiotic resistance and its impact on the dental community.
AB  - There is significant evidence that the global problem of microbial resistance to
      antibiotics has reached the dental community both in our practices and our family
      lives. This paper will present a global overview of microbial resistance, discuss
      how this problem directly affects the dental community, and show what we can do
      to change the situation, both as concerned citizens and as dental health care
      practitioners.

PMID- 11324058
TI  - Oral pathology quiz #28. Case 2. Parulis.

PMID- 11324059
TI  - Oral pathology quiz #28. Case 3. Pleomorphic adenoma.

PMID- 11324060
TI  - Oral pathology quiz #28. Case 4. Central ossifying fibroma.

PMID- 11324061
TI  - Providing patient-friendly financial options.
AB  - Having flexible payment options ensures that patients will have all of the
      motivation and information that they need to accept care in your office. The HCCC
      simply offers you the chance to make more expensive treatment available to those
      who need or want it. The small cost of using a HCCC program more than pays for
      itself--in fact, it costs less than one-third of what you would spend if you were
      to bill these patients instead. Having consistent financial policies and flexible
      payment options can dramatically increase your office's productivity and
      profitability, while expressing your commitment to customer service and high
      quality dentistry.

PMID- 11324062
TI  - Dental X-rays may predict fatal heart attacks, strokes.

PMID- 11324063
TI  - Be careful out there.

PMID- 11324064
TI  - The bimaxillary or dual arch mouthguard for boxing.

PMID- 11324065
TI  - The Renaissance. Dental millennium series. Part III.

PMID- 11324066
TI  - A guide to evaluating epidemiological studies.
AB  - Epidemiological studies that fail to follow established principles can lead to or
      promote false assumptions. Attention to the principles of epidemiological studies
      and avoidance of extrapolation beyond the data can remove much of the confusion
      that presently exists among the health professions and general public. This
      article offers guidelines to evaluating epidemiological studies.

PMID- 11324067
TI  - The dental network: the interrelationships of specialists and general dentists.
AB  - There is an unsubstantiated belief that patients are referred only to dental
      specialists and not from specialist to general dentist. For the most part, a high
      percentage of new patients to oral surgeons, periodontists and endodontists are
      generated from general practices. These specialists, in turn, could be a source
      of new patients to the general practitioner. Often the specialists have
      information about which dentists may be selling their practices or looking for an
      associate. This would be valuable if a dentist wanted to expand or merge a
      practice, or for a dentist just beginning to practice. A specialist can influence
      the patient to accept a restorative treatment plan, or perhaps recommend
      treatment that the patient requires. The GP should make an effort to attend study
      clubs, dental society meetings, and to meet the local specialists. It is just as
      important for the GP to be known by specialists as it is for specialists to be
      known by the GP.

PMID- 11324068
TI  - Treating the accident victim and getting paid.

PMID- 11324069
TI  - Palladium: today's most popular alloy.

PMID- 11324070
TI  - Stage I surgical indexing: clinical and laboratory procedures.
AB  - This article will describe the clinical and laboratory procedures used to treat a
      patient with implant retained crowns including Stage I indexing, fabrication of
      fixed provisional crowns to be inserted at the time the implants were uncovered
      (Stage II surgery), and the insertion of the definitive cement-retained crowns
      after the soft tissues had healed. All of the components described in this
      article were made by Implant Innovations, Inc., Palm Beach Gardens, FL. The
      reader may consider this type of treatment using components made by various
      manufacturers.

PMID- 11324071
TI  - Double structure on implants.

PMID- 11324073
TI  - Establishing and maintaining a successful laboratory/dentist relationship.

PMID- 11324072
TI  - If an economy denture is processed with less expensive teeth and acrylics versus
      premium acrylics and teeth, what is the cost savings for longevity versus lesser
      products used, if any?

PMID- 11324074
TI  - Bill would establish pilot project for denturism in Kentucky.
AB  - HB 238 has been reported favorably to the floor of the House of Representatives
      by the Committee on Licensing and Occupations, but has not yet been acted upon by
      the full House. When asked whether he thought his legislation would be approved,
      Representative Burch said he thought the bill had a "50-50" chance of passing the
      Kentucky legislature this year. Sources within the Kentucky dental laboratory and
      dental communities disagree on the legislation's chances for passage. Some within
      the industry feel the legislation simply does not have enough votes to pass the
      General Assembly, primarily because of opposition from the Kentucky Dental
      Association. Others speculate that the bill has a better opportunity to be
      approved this year than it did in the previous years when it was introduced. The
      Kentucky General Assembly adjourns its session for the year 2000 on April 12, so
      there will be a quick answer to the question of whether HB 238 will be approved.
      The May issue of this column will provide details.

PMID- 11324075
TI  - Do marriage problems affect fathering more than mothering? A quantitative and
      qualitative review.
AB  - The important question of whether marital problems disrupt fathering more than
      mothering is addressed in (a) a quantitative review of evidence on marital
      conflict and parenting in intact families, and (b) a qualitative review of
      research on mother and father involvement with their children following divorce.
      We conclude that (a) there is limited evidence that, relative to mothering,
      fathering is more likely to be affected by marital conflict, but suggest that (b)
      marital status (i.e., divorce) affects fathering notably more than it affects
      mothering. We further suggest that marital problems may disrupt father
      involvement which, in turn, weakens the quality of father-child relationships;
      there likely are multiple alternative pathways through which marriage problems
      affect parenting, including both "spillover" and "compensation"; researchers need
      to examine more carefully how marital problems disrupt coparenting; child age and
      gender may moderate linkages between the parental and marital subsystems; and
      coparenting, marital happiness, and the institution of marriage itself may be
      essential first avenues of intervention for those who wish to improve or maintain
      fathers' involvement with their children.

PMID- 11324076
TI  - Fathering and early onset conduct problems: positive and negative parenting,
      father-son attachment, and the marital context.
AB  - Research literature linking negative and positive aspects of the father-child
      relationship with early onset conduct problems is reviewed. Evidence from the
      Preschool Families Project, a longitudinal study of clinic-referred preschool
      boys at risk for conduct disorder, is presented, including previously unpublished
      data on father-child attachment. Both negative (e.g., harsh, angry, and
      physically punitive) and positive (involvement, warmth, and secure attachment)
      dimensions of fathering, as well as aspects of the marital relationship, appear
      to be associated with the emergence of early onset conduct problems.

PMID- 11324077
TI  - Behavioral family interventions for improving child-rearing: a review of the
      literature for clinicians and policy makers.
AB  - This paper reviews evidence that behavioral family interventions are effective at
      improving child-rearing in distressed families and families with children
      exhibiting disruptive behavior. Essential therapeutic strategies offered within a
      collaborative therapeutic process are identified. Exemplary materials for parents
      and clinicians are identified. Differences between behavioral family
      interventions and two popular press parenting approaches are highlighted,
      including the lack of empirical support for these widely used programs and the
      advice they offer which runs counter to behavioral approaches. Recommendations
      are offered for combining behavioral family interventions with other empirically
      supported approaches, promoting more widespread use of empirically supported
      treatments, such as behavioral family interventions, and the need for a public
      health perspective on family functioning, involving collaboration among
      clinicians, policy makers, and researchers.

PMID- 11324078
TI  - Parental monitoring and the prevention of child and adolescent problem behavior:
      a conceptual and empirical formulation.
AB  - The present report accomplishes three goals. First, to provide an empirical
      rationale for placing parental monitoring of children's adaptations as a key
      construct in development and prevention research. Second, to stimulate more
      research on parental monitoring and provide an integrative framework for various
      research traditions as well as developmental periods of interest. Third, to
      discuss current methodological issues that are developmentally and culturally
      sensitive and based on sound measurement. Possible intervention and prevention
      strategies that specifically target parental monitoring are discussed.

PMID- 11324079
TI  - Proof first, profit second.

PMID- 11324080
TI  - Ceramometal bonded inlays and onlays.
AB  - Porcelain-fused-to-metal (PFM) is presently the most popular crown and bridge
      technique. Its success is attributable to the use of a metal substructure to
      support the porcelain, resulting in good esthetics, limited ceramic flexure, and
      better longevity than all-porcelain restorations. A new concept suggests
      encapsulating the metal substructure with ceramic and placing the insert under
      the occlusal surface, thereby combining the best properties of the esthetics of
      porcelain and the support of metal to achieve improved restorations.

PMID- 11324081
TI  - The science of communicating the art of esthetic dentistry. Part I: Patient
      dentist-patient communication.
AB  - Many contemporary restorative procedures are primarily esthetically driven, and
      patients have high expectations. It is imperative for the restorative dentist to
      understand patients' desires and expectations prior to initiating irreversible
      therapy. It is equally important for patients to understand the anatomic and
      technical limitations inherent with restorative therapy.

PMID- 11324082
TI  - Shear bond strengths of one-bottle adhesives to oil-contaminated enamel.
AB  - PURPOSE: To evaluate resin bond strength to enamel contaminated with handpiece
      oil. MATERIALS AND METHODS: Bovine teeth were randomly assigned to six groups of
      20 teeth each for treatment with one of six different bonding systems (five one
      bottle and one multibottle). For each system, 10 enamel specimens were
      contaminated with handpiece oil before acid-etching and 10 were contaminated
      after acid-etching. The enamel was etched for 15 seconds using 35% phosphoric
      acid. Following adhesive application, composite resin was bonded using a gelatin
      capsule technique. Shear bond strengths from the two contaminated groups were
      compared to bond strengths to uncontaminated enamel obtained from a previous
      study that was performed by the same group of investigators, using the same
      facility, materials, and methods. RESULTS: Two-way analysis of variance (ANOVA)
      showed that the factor "surface contamination" did not have a significant effect
      on bond strength (p > .542). The type of adhesive and the interaction of adhesive
      and surface contamination were significant (p < .0001 and p < .003,
      respectively). When oil was applied before etching, mean bond strengths ranged
      from 18.0 +/- 4.8 MPa for OptiBond SOLO (Kerr Corp., Orange, California) to 25.3
      +/- 5.6 MPa for Tenure Quik with Fluoride (Den-Mat Corp., Santa Maria,
      California). With oil applied after etching, bond strengths ranged from 18.4 +/-
      8.0 MPa for Tenure Quik with Fluoride to 27.4 +/- 5.4 MPa for Single Bond (3M
      Dental Products, St. Paul, Minnesota). For the same adhesive, comparing
      uncontaminated and "oil-before-etch" contaminated groups, the only statistically
      significant difference in bond strengths was for OptiBond SOLO: 21.8 +/- 4.0 MPa
      (uncontaminated) versus 18.0 +/- 4.8 MPa (oil before etch). Comparing
      uncontaminated and "oil-after-etch" groups, the only statistically significant
      difference was for Tenure: 24.5 +/- 5.7 MPa (uncontaminated) and 18.4 +/- 8.0 MPa
      (oil after etch).

PMID- 11324083
TI  - Amalgam substitutes: a critical analysis.
AB  - PURPOSE: Quality standards for restorations recently have been defined in
      Switzerland. Amalgam substitutes must meet restoration Grade 2 requirements
      (i.e., pulp and dental hard substance must be preserved, and both form and
      function of the tooth have to be reconstituted). The pertinent operative
      technique has to be simple and amalgam-like. A minimum service life of 8 years is
      required. This in vitro study investigated the clinical potential of several
      amalgam substitutes, taking into account the operative requirements, the defined
      restorative guidelines, and the required service life. MATERIALS AND METHODS:
      Potential amalgam substitutes evaluated in this study included compomers
      (Compoglass, Dyract, Dyract AP, Elan, F 2000) and resin-based composites (Alert,
      Ariston, Definite, Nulite, Solitaire, Surefil). The composites Adaptic and Tetric
      Cream, using a simplified placement technique, were tested as negative and
      positive controls, respectively. Marginal adaptation and wear properties were
      measured in vitro in mixed Class II cavities. Relative radiopacity was measured
      in terms of millimeters of equivalent aluminum. RESULTS: All compomers showed a
      radiopacity of 2.5 mm or more aluminum. Only Dyract AP and Elan were more wear
      resistant than amalgam. After stressing, the percentage of continuous margin was
      at best 31% overall and 17% in dentin only. Among resin-based composites, the
      minimum requirements of radiopacity were fulfilled only by Alert, Surefil, and
      Tetric. Only Definite, Surefil, Solitaire, and Tetric exhibited wear resistance
      greater than amalgam. After stressing, the best marginal qualities were 41%
      continuous margin overall, and 8% in dentin only.

PMID- 11324084
TI  - Effects of fluoride varnish on color of esthetic restorative material.
AB  - PURPOSE: This study determined the color stability of a compomer, hybrid ionomer,
      and composite after staining with three fluoride varnishes. MATERIALS AND
      METHODS: Five disks (10 mm in diameter, 2 mm thick) of each material were
      prepared in a mold and incubated at 100% relative humidity at 37 degrees C for 24
      hours. Duraphat, Duraflor, FluorProtector, and water (control) were applied to
      the disks, which were subsequently brushed with a soft toothbrush and dentifrice.
      Color was measured at baseline, after staining, and after brushing using CIE
      L*a*b* (source C) against white background on a reflection spectrophotometer, and
      color change (delta E*) was calculated. Means (n = 5) and standard deviations
      were calculated and compared using a repeated-measures analysis of variance
      (ANOVA). Tukey-Kramer intervals (p = .05) were calculated to compare means.
      RESULTS: Varnishes Duraflor and Duraphat caused perceptible color changes (delta
      E* > 3.3) in compomer, hybrid ionomer, and composite after application; however,
      FluorProtector did not affect the color of the materials. After brushing, none of
      the materials exhibited perceptible values of delta E*, except the composite with
      Duraflor (delta E* = 5.4).

PMID- 11324085
TI  - Fiber-reinforced inlay fixed partial dentures: maximum preservation of dental
      hard tissue.

PMID- 11324086
TI  - A histological procedure to determine dental age.
AB  - Sclerosis of dentine has become one of the well established indicators of ageing
      and age determination. In this study a new technique was reported where a
      photomicrographic image of a cross section of sclerotic dentine was converted to
      a grey scale of 256 tones and then reduced to black and white and read by
      computer using specially developed software. A regression analysis was applied to
      a sample of 62 teeth (age range 17-84 years) and an age determination within an
      error limit of 11 years was obtained. Using a Neural Network software however the
      error was reduced to 8 years.

PMID- 11324087
TI  - Bitemarks in chocolate: a case report.
AB  - Police investigating a theft from a chocolate factory recovered three pieces of
      chocolate with irregular fractured surfaces displaying a pattern of marks made by
      human teeth. A highly accuracy dental impression material was used to prepare
      casts of these marks which were examined and photomicrographed, confirming that
      they had in fact been produced by human teeth. Casts and photomicrographs of the
      suspect's teeth were made in order to record the fine details of the casts of the
      dentition. Unique characteristics evident on these casts included a small notch
      on the incisal edge of the upper right lateral incisor, wear facets on the
      incisal edges of the upper central incisors and on the lower right lateral
      incisor and a space of approximately 1.5 mm between the upper left central
      incisor and lateral incisor which was rotated about 20 degrees distally. Both
      direct and photomicrographic comparisons between the casts of the chocolates and
      of the suspect's dentition revealed correspondence between their unique
      characteristics.

PMID- 11324088
TI  - Identification concept and the use of probabilities in forensic odontology--an
      approach by philosophical discussion.
AB  - This paper questions the practitioners' deterministic approach(es) in forensic
      identification and notes the limits of their conclusions in order to encourage a
      discussion to question current practices. With this end in view, a hypothetical
      discussion between an expert in dentistry and an enthusiastic member of a jury,
      eager to understand the scientific principles of evidence interpretation, is
      presented. This discussion will lead us to regard any argument aiming at
      identification as probabilistic.

PMID- 11324089
TI  - Autopsy techniques in the orofacial area and maceration using enzyrim.
AB  - The current methods of maceration are imperfect and the chemicals involved are
      toxic, offensive smelling, difficult to clean up and difficult to dispose of. The
      use of enzymes for maceration accelerates the catalytic process markedly and the
      method is cheap, easy to handle, non-toxic, practical and totally biodegradable.

PMID- 11324090
TI  - Use of buccal epithelial cells for PCR amplification of large DNA fragments.
AB  - The analysis of human DNA is widely employed in the genetic studies of families
      and populations, and in most cases is performed with samples obtained from
      peripheral blood. The use of buccal epithelial cells as a source of DNA for PCR
      amplifications has several advantages over blood sampling but has only been used
      to amplify small fragments of DNA. Its use in forensic analysis has been limited
      to cases where the sampling of peripheral blood is not feasible. In the present
      study we show that buccal epithelial cells are a reliable source of DNA for the
      PCR amplification of high molecular mass fragments, which could be used in large
      scale population sampling. Since most PCR gender-typing systems rely on the
      amplification and electrophoretic separation of the amelogenin gene, our results
      show that buccal epithelial cells may be the preferred source of DNA for gender
      typing analysis.

PMID- 11324091
TI  - The nuts and bolts of behavioral observation of marital and family interaction.
AB  - Despite considerable discussion in the literature about the advantages of
      observational research and the relative benefits of different coding systems and
      strategies, little is written about the actual implementation of this assessment
      strategy. This paper presents an overall framework as well as the essential
      components involved in collecting (selection of task, setting, unit of analysis,
      and coding system) and coding (transcribing, selecting and training coders,
      transforming data, and analyzing reliability) of observational data. To achieve
      success with observational methods, we emphasize several issues, including (a)
      the research question as the motivator for all decisions, (b) the
      interrelatedness of tasks, and (c) the implications of decisions early in the
      process for later stages of analysis and interpretation. Investigators are
      encouraged to communicate the details of their observational and coding
      procedures so that these methods are readily accessible for purposes of
      replication and comparison.

PMID- 11324092
TI  - Developmental and adjustment issues of gay, lesbian, and bisexual adolescents: a
      review of the empirical literature.
AB  - Various studies have reported adjustment problems experienced by gay, lesbian,
      and bisexual (GLB) adolescents. A primary purpose of this paper is to critically
      review this literature. Difficulties that have been studied include past suicide
      attempts, substance use and abuse, conduct problems, and academic concerns. For
      example, a considerable number of GLB youth report a history of suicide attempts,
      with prevalence rates ranging from 11 to 42%. However, among other methodological
      concerns, studies in this area have not used a comparison sample of heterosexual
      youths. Characteristics of development particular to GLB adolescents are
      described, the empirical research on adjustment issues is reviewed, and potential
      risk and protective factors for GLB youths are discussed.

PMID- 11324093
TI  - Critical issues in the assessment of child sexual abuse.
AB  - This article explores the feasibility of using standardized psychometric methods
      in the initial stages of an investigation of child sexual abuse; methods that are
      less intrusive and therefore less damaging to children and their families. We
      review the complex conceptual and research issues that arise from attempts to
      assess the many-sided aspects of child sexual maltreatment. Among those
      considered in both the clinical and research spheres are problems of definition
      and diagnosis; limitations of clinical interviews, and a variety of direct and
      indirect psychological instruments used for investigating sexual maltreatment and
      risk assessment; the inadequacies of experimental designs; and also the
      political, practical, and ethical restraints that hinder research in this area.
      It is argued that there is insufficient evidence based on controlled studies or
      standardized normative tests to advocate any simple, unidimensional methodology
      for the screening task. However, recommendations are put forward for the
      cautious, conjoint use of several procedures in a multidimensional approach to
      assessing child sexual abuse. Suggestions are also made for future research and
      development.

PMID- 11324094
TI  - Behavioral genetics as a tool for developmental psychology: anxiety and
      depression in children and adolescents.
AB  - Over the past decade there has been a huge increase in the number of behavioral
      genetic studies looking into anxiety and depression in children and adolescents.
      There are now enough data in this area to make a review of the results useful.
      This paper begins with an outline of the methods used in such research and moves
      on to review the results in extant studies. Overall, these studies indicate
      modest to moderate genetic influence on both anxiety and depression. However,
      behavioral genetic methods are also paramount for exploring environmental
      influences in addition to genetic influences. Shared environment (that which
      makes family members resemble one another) is rarely identified in adult studies
      of personality or psychopathology and does not appear to be a significant
      influence for depression but it is for anxiety. Nonshared environment, which
      makes family members differ from one another, is found to be a significant
      influence for both anxiety and depression. Patterns within these results due to
      rater effects, age effects, sex effects, the precise phenotype measured, and the
      study design are explored.

PMID- 11324096
TI  - The EARLY ALLIANCE prevention trial: an integrated set of interventions to
      promote competence and reduce risk for conduct disorder, substance abuse, and
      school failure.
AB  - Describes the EARLY ALLIANCE interventions, an integrated set of four programs
      designed to promote competence and reduce risk for early-onset conduct disorder,
      substance abuse, and school failure. These interventions are evaluated as part of
      a prevention trial that begins at school entry and targets child functioning and
      socializing practices across multiple contexts (school, peer group, family) and
      multiple domains (affective, social, and achievement coping-competence). The
      paper presents the conceptual foundation of the four interventions, including a
      synopsis of the risk and protective factors associated with conduct disorder and
      related outcomes, and of the coping-competence model driving EARLY ALLIANCE. The
      developmental rationale, intended impact, and procedures are described for each
      intervention: a universally administered classroom program and indicated, peer,
      reading-mentoring, and family programs. Interventions are currently being tested
      in a prevention trial, which is briefly summarized.

PMID- 11324095
TI  - Conduct disorder in girls: a review of the literature.
AB  - The study of Conduct Disorder (CD) has primarily been limited to boys. The lack
      of research resulted from a premise that CD in girls was rare. However, CD in
      girls is a relatively common psychiatric diagnosis, and appears to be associated
      with several serious outcomes, such as Antisocial Personality Disorder and early
      pregnancy. Understanding gender differences in the course and severity of CD may
      lead to important information about etiology. Empirical studies on precursors,
      developmental course, risk factors and treatment for CD in girls are reviewed,
      while highlighting similarities and differences between girls and boys.
      Generally, CD symptoms in girls are stable. Precursors to CD in girls probably
      include Oppositional Defiant Disorder and temperamental factors, but also may
      include certain negative cognitions. What distinguishes CD in girls is the high
      risk they have to develop comorbid conditions, especially internalizing
      disorders. Risk factors for CD in girls partly overlap with those known for boys,
      but some factors appear to be highly salient for girls. Finally, there may be
      some significant effects of gender on treatment efficacy. Implications of these
      findings for future etiologic research are discussed.

PMID- 11324098
TI  - Dating the origin of metazoan body plans.

PMID- 11324097
TI  - Birds, trees, and stems.

PMID- 11324099
TI  - Anteroposterior patterning by mutual repression of orthodenticle and caudal-type
      transcription factors.
AB  - Members of the Otx (orthodenticle) and Cdx (caudal) families of homeodomain
      transcription factors are expressed in similar embryonic regions in all animal
      groups and have been shown to be directly involved in anteroposterior patterning
      in a number of species. In the amphibian Xenopus laevis, the Otx family gene
      Xotx2 and the Cdx family gene Xcad3 are both expressed within the early dorsal
      organizer. We show that they have mutually repressive activities, suggesting that
      they play a crucial role in the early regionalization of the organizer into
      anterior and posterior territories. Xotx2 can act both as an activator and
      repressor of gene expression depending on context. A form of Xotx2 that acts
      exclusively as a repressor (OtxEn-R) was made by fusing the Xotx2 homeodomain to
      the Drosophila melanogaster engrailed transcriptional repressor domain.
      Overexpression of this protein in vivo indicates that OtxEn-R antagonizes the
      activating function of endogenous Xotx2 for anterior marker genes such as XCG and
      goosecoid but retains the ability to repress the expression of posterior markers
      such as Xcad3 and Xbra. OtxEn-R overexpression causes a severe derangement of
      anterior development, resulting in the loss of cement gland, eyes, stomodeal
      opening, and pharynx. The specification and development of anterior neural
      structures is dramatically abnormal up to and including the isthmic signaling
      center at the midbrain/hindbrain junction. This study provides good evidence that
      Xenopus Otx2 is required for normal head patterning and the process of anterior
      neural specification. We propose that a mutually antagonistic relationship
      between Otx and Cdx factors is a basic aspect of anteroposterior patterning in
      all vertebrates.

PMID- 11324100
TI  - AmphiPax3/7, an amphioxus paired box gene: insights into chordate myogenesis,
      neurogenesis, and the possible evolutionary precursor of definitive vertebrate
      neural crest.
AB  - Amphioxus probably has only a single gene (AmphiPax3/7) in the Pax3/7 subfamily.
      Like its vertebrate homologs (Pax3 and Pax7), amphioxus AmphiPax3/7 is probably
      involved in specifying the axial musculature and muscularized notochord. During
      nervous system development, AmphiPax3/7 is first expressed in bilateral
      anteroposterior stripes along the edges of the neural plate. This early neural
      expression may be comparable to the transcription of Pax3 and Pax7 in some of the
      anterior neural crest cells of vertebrates. Previous studies by others and
      ourselves have demonstrated that several genes homologous to genetic markers for
      vertebrate neural crest are expressed along the neural plate-epidermis boundary
      in embryos of tunicates and amphioxus. Taken together, the early neural
      expression patterns of AmphiPax3/7 and other neural crest markers of amphioxus
      and tunicates suggest that cell populations that eventually gave rise to
      definitive vertebrate neural crest may have been present in ancestral
      invertebrate chordates. During later neurogenesis in amphioxus, AmphiPax3/7, like
      its vertebrate homologs, is expressed dorsally and dorsolaterally in the neural
      tube and may be involved in dorsoventral patterning. However, unlike its
      vertebrate homologs, AmphiPax3/7 is expressed only at the anterior end of the
      central nervous system instead of along much of the neuraxis; this amphioxus
      pattern may represent the loss of a primitive chordate character.

PMID- 11324101
TI  - Hemichordates and deuterostome evolution: robust molecular phylogenetic support
      for a hemichordate + echinoderm clade.
AB  - Hemichordates were traditionally allied to the chordates, but recent molecular
      analyses have suggested that hemichordates are a sister group to the echinoderms,
      a relationship that has important consequences for the interpretation of the
      evolution of deuterostome body plans. However, the molecular phylogenetic
      analyses to date have not provided robust support for the hemichordate +
      echinoderm clade. We use a maximum likelihood framework, including the parametric
      bootstrap, to reanalyze DNA data from complete mitochondrial genomes and nuclear
      18S rRNA. This approach provides the first statistically significant support for
      the hemichordate + echinoderm clade from molecular data. This grouping implies
      that the ancestral deuterostome had features that included an adult with a
      pharynx and a dorsal nerve cord and an indirectly developing dipleurula-like
      larva.

PMID- 11324102
TI  - Expression of Distal-less in molluscan eggs, embryos, and larvae.
AB  - Distal-less (Dll) is best known as a transcription factor involved with "limb
      patterning" in Drosophila melanogaster. Observations of both deuterostome and
      protostome phyla have led to the suggestion that some aspect of this gene's
      function in "appendage" or proximal-distal "outgrowth" development is conserved.
      Here we explore the possibility of other conserved roles operating earlier in
      development. We examine the expression of DLL protein during the early
      development of two molluscan classes, Polyplacophora (chiton) and Gastropoda
      (snail). Using an antibody approach, we find DLL expression in the oocytes of a
      chiton (Mopalia muscosa) and in the pregastrulae through early veliger larvae of
      a marine snail (Kelletia kelletii). We observe antibody localization in the
      oocyte, nuclear expression in all cells of the pregastrulae, and predominant
      expression in the ectoderm of postgastrulae and early veliger larvae. Comparison
      of our observations on spiralian taxa, thought to have conservative development
      with previous work, primarily on deuterostomes, suggests the possibility of an
      ancient role(s) for DLL in early development. Possible functions appear to
      include maternal and zygotic involvement in the establishment of embryonic
      polarity, involvement in the process of germ layer formation, and a role in the
      specification and/or differentiation of ectoderm/epithelia. We note that the
      exploration of conserved gene function in early development may be clarified by
      examining taxa whose early development has putatively not been subject to
      dramatic evolutionary change.

PMID- 11324103
TI  - Characterization of MADS genes in the gymnosperm Gnetum parvifolium and its
      implication on the evolution of reproductive organs in seed plants.
AB  - Gnetales, one of the extant gymnosperm orders, has traditionally been recognized
      to be most closely related to flowering plants, because the reproductive organ of
      Gnetales has some morphological characteristics similar to flowering plants. Most
      recent molecular phylogenetic studies do not support the sister relationship of
      the Gnetales and flowering plants, but instead support a close relationship
      between Gnetales and other extant gymnosperms. The MADS genes are transcription
      factors, some of which are involved in reproductive organ development in
      flowering plants. To resolve the discrepancy in phylogenetic inferences, and to
      provide insights into the evolution of reproductive organs in seed plants, four
      MADS genes (GpMADS1-4) were cloned from Gnetum parvifolium. GpMADS2 is likely to
      be a pseudogene and the other three genes were characterized. A MADS gene tree
      based on partial amino acid sequences showed that GpMADS3 is included in the AGL6
      group, but the other two genes do not cluster with any previously reported MADS
      gene. The three GpMADS genes were expressed during the early stage of ovule
      development in the differentiating nucellus and three envelopes. A comparison of
      MADS gene expression among conifers, Gnetum, and flowering plants suggests that
      the comparable reproductive organs in Gnetum and flowering plants evolved in
      parallel, and is likely to support the homology between the ovule-ovuliferous
      scale complex of conifers and the Gnetum ovules, including the three envelopes.

PMID- 11324104
TI  - Teaching a new philosophy.

PMID- 11324105
TI  - 21st century dentistry.

PMID- 11324106
TI  - 1999 year in review.

PMID- 11324107
TI  - A new century wish list.

PMID- 11324108
TI  - The pacesetter for the profession.

PMID- 11324110
TI  - Tiniest patients need care too.

PMID- 11324109
TI  - Lester Monroe Dipswich--man of the century.

PMID- 11324111
TI  - Update on the epidemiology of HIV/AIDS in the United States.
AB  - During the past 20 years, the epidemic of human immunodeficiency virus and
      acquired immunodeficiency syndrome in the United States has continually evolved.
      Beginning in the mid-1990s, the numbers of annual AIDS cases and AIDS deaths have
      decreased, due in large measure to effective combination anti-retroviral
      therapies, which prolong the survival of people infected with HIV and delay
      progression to AIDS. This has resulted in an increase in the number of people
      living with HIV infection or AIDS. Increasing proportions of AIDS cases are
      occurring among women, racial/ethnic minorities, and people infected through
      heterosexual transmission. Dental care professionals are faced with the challenge
      of providing quality dental care to this ever-increasing population.

PMID- 11324112
TI  - Current concepts in HIV pathogenesis and treatment.
AB  - Over the past several years, great strides have been taken in the understanding
      and treatment of the human immunodeficiency virus. Death rates due to HIV have
      declined significantly since the introduction of protease inhibitors. Despite the
      advances in the field, health practitioners are still quite limited in their
      ability to curb this disease: 40,000 new HIV infections occur every year in the
      United States. This article will review the new advances in pathogenesis and
      treatment and discuss the limitations faced in treating the disease.

PMID- 11324113
TI  - Current oral manifestations of HIV infection.
AB  - The oral manifestations of human immunodeficiency virus infection have changed
      drastically since the introduction of the highly active anti-retroviral therapy
      (HAART) in developed countries. Recent studies have documented significant
      reductions in morbidity and mortality rates among HIV-infected patients on HAART.
      This article focuses on the latest information about the oral manifestations of
      HIV infection and will discuss the impact of HAART.

PMID- 11324114
TI  - Oral HIV transmission.
AB  - Although transmission of HIV through casual contact with saliva has not been
      shown, oral exposure to HIV-infected semen, blood, and breast milk can lead to
      infection. Unprotected orogenital contact, especially receptive oral intercourse,
      is associated with greater risk of HIV transmission than previously thought. The
      salivary anti-HIV properties, the local and systemic immunologic responses, the
      local mucosal integrity, and the level of infectious HIV present at the oral
      mucosal site all influence the potential for HIV infection through the oral
      mucosa. Although more information on the exact mechanisms of oral HIV
      transmission are necessary, based on the current understanding of this process,
      educational HIV prevention methods must focus on the potential risks associated
      with orogenital sexual behaviors.

PMID- 11324115
TI  - HIV risk assessment: building on dentistry's history of promoting health.
AB  - Dentists have demonstrated a willingness to look beyond the mouth and consider
      the patient's overall presentation in a number of health-related areas. The HIV
      pandemic is another opportunity to involve the dentist in overall health issues
      through identification of those individuals at risk for acquiring HIV. This risk
      assessment activity can be facilitated through the use of a structured risk
      assessment algorithm that is presented in detail. The purpose of this algorithm
      is to encourage dentists--when they notice specific conditions or become aware of
      risky behaviors--to talk with their patients about HIV/AIDS and how the patient
      may be at risk. The historic success dentists have achieved in conveying
      information about the prevention of disease and promotion of health should
      bolster their resolve to expand their discussions with patients to include an HIV
      risk assessment.

PMID- 11324116
TI  - The AETC: a resource for dental professionals.

PMID- 11324117
TI  - What the dentist should know about a patient with HIV/AIDS.
AB  - Chances are good that oral health care providers will treat someone with
      diagnosed or undiagnosed HIV during their careers. The Centers for Disease
      Control and Prevention estimate that 650,000 to 900,000 U.S. residents are living
      with HIV infection, more than 200,000 of whom are unaware of their infection. As
      with any medical condition, it is possible for a dentist to do great harm by
      ignoring systemic manifestations of HIV. On the other hand, dentists who are
      ignorant of modern HIV disease management often request unnecessary medical
      consultations resulting in dental treatment delays. Since 1996, the growing use
      of highly active anti-retroviral therapy and ultrasensitive viral load testing
      has changed the picture of the dental patient with HIV. The goal of this article
      is to update and summarize information the oral health care provider needs to
      safely treat a person with HIV/AIDS. It is not intended to replace previous
      comprehensive publications on HIV and dentistry, as they are still excellent
      resources for information. Here, simple instructions for physical evaluation of a
      patient with HIV/AIDS will be presented and steps for determining safe procedures
      explained.

PMID- 11324119
TI  - Providing dental care for disabled patients.

PMID- 11324118
TI  - Getting the job done.

PMID- 11324120
TI  - Managing the patient with severe respiratory problems.
AB  - The dental management of patients with severe respiratory problems continues to
      be a significant challenge to the dental health care practitioner. Chronic
      obstructive pulmonary diseases, such as chronic bronchitis and emphysema, are the
      fourth leading cause of death in the United States. Asthma has increased in
      prevalence during the past 20 years, and the rate of death from this chronic
      inflammatory disease of the airways has also risen despite recent advances in
      medical treatments. This article will review the pathophysiology and medical
      treatment modalities for these chronic pulmonary diseases, as well as discuss the
      recognition and management of dental patients with these diseases and provide an
      understanding on how to avoid precipitating factors that could initiate an acute
      episode in the dental care setting.

PMID- 11324121
TI  - Herbal supplements: considerations in dental practice.
AB  - Over-the-counter natural herb products constitute a rapidly growing market in the
      United States. As with conventional medications, the health care provider needs
      to be aware of these products' effects, side effects, advantageous synergies, and
      possible or probable adverse drug reactions. This paper will present 20 of the
      most frequently used herbs in the United States and discuss appropriate
      precautions and herb-drug interactions of possible concern in clinical dental
      practice.

PMID- 11324122
TI  - Local anesthetics and medically complex patients.
AB  - As the population ages and medical science advances, more and more patients with
      complex medical histories will be seeking care in private dental practices. This
      paper will review a variety of disease entities as well as potential drug
      interactions pertinent to the use of local anesthetic agents in medically complex
      patients.

PMID- 11324123
TI  - Antibiotic prophylaxis for selected implants and devices.
AB  - Certain implants or devices are widely believed to put patients at risk from oral
      bacteremia. They include but are not limited to intravascular access devices,
      solid organ transplants, vascular grafts, coronary artery stents, breast
      implants, and penile prostheses. The purpose of this article is to review the
      risk of implant or device infection from transient bacteremia of oral origin and
      to provide recommendations for appropriate dental management. Since dental
      treatment bacteremias are a very rare cause of metastatic infections, attributing
      causality to dental treatment procedures can be viewed as unfounded in almost all
      cases.

PMID- 11324124
TI  - Perception or reality?

PMID- 11324125
TI  - Eat your way to better dental health.

PMID- 11324126
TI  - An in-vitro comparison of the radiographic and actual gutta-percha terminus.
AB  - The purpose of this study was to investigate the difference between the
      radiographic gutta-percha terminus and the actual gutta-percha terminus of human
      molars by comparing radiographic obturation results with actual obturation
      results. Forty maxillary palatal roots and 50 mandibular distal roots were
      randomly selected from a population of 540. They were then mounted in stone and
      radiographed. Conventional endodontic therapy was completed using stainless-steel
      K files and lateral condensation. Each radiographic gutta-percha terminus was
      evaluated under 4.5x magnification by three examiners following the completion of
      root canal therapy. These results were recorded. Each tooth was then removed from
      its mounting, and the actual gutta-percha terminus was evaluated under 4.5x
      magnification. These results were recorded and compared to the radiographic gutta
      percha terminus results. In all 90 teeth examined, the actual gutta-percha
      terminus was equal to or longer than the radiographic gutta-percha terminus. In
      the 50 mandibular distal roots, the actual gutta-percha terminus averaged 0.645
      mm longer than the radiographic gutta-percha terminus. In the 40 maxillary
      palatal roots, this difference measured 0.6375 mm.

PMID- 11324127
TI  - Comparison between a hand stainless-steel K file and a rotary NiTi 0.04 taper.
AB  - Straightening of curved canals is one of the most common procedural errors in
      endodontic instrumentation. It can lead to ledging, perforation, and stripping of
      the canal. The problem is commonly encountered when root canal preparation is
      performed in curved molars. The purpose of this study was to compare the results
      of root canal preparation by undergraduate dental students using traditional
      stainless-steel 0.02 taper K files to results obtained using rotary nickel
      titanium 0.04 taper files. One hundred ninety six extracted teeth comprising
      maxillary and mandibular first molars were used. Preoperative and postoperative
      radiographs of each tooth were taken. Graduate endodontic residents evaluated the
      radiographs according to the evaluation criteria used by the endodontic
      department. The presence of errors--such as stripping, perforation, ledging,
      transportation, zipping, and instrument breakage--was recorded by examining the
      radiographs.

PMID- 11324129
TI  - Dye leakage study: comparing conventional and new techniques.
AB  - The purpose of this study was to compare the degree of dye penetration of
      Thermofil and Simplifill to standard lateral condensation using AH26 plus. Forty
      five human maxillary incisors were instrumented and obturated with three
      different methods: Rotary Profile with the Thermofil method and AH-26 Plus
      sealer, Rotary Lightspeed with the Simplifill method and AH-26 Plus sealer, and
      hand file with lateral condensation and AH-26 Plus. An additional 45 teeth were
      used as positive controls in three separate but corresponding groups, and another
      15 were in negative control group. Apical leakage was measured and evaluated on
      both the internal canal surfaces and the obturation material itself. The results
      showed that there was a significant difference between the control and obturated
      groups but no significant difference between any obturation groups.

PMID- 11324128
TI  - Gutta-percha: a look at the need for sterilization.
AB  - Many have argued that the prevention of contamination becomes a problem when
      gutta-percha cones are used to obturate the root canal space. This study
      evaluated the extent of contamination of commercially available gutta-percha
      cones taken directly from the manufacturer's box. Results show that if gutta
      percha is not intentionally contaminated, there is no need for chemical
      decontamination before obturation.

PMID- 11324130
TI  - A vision of the future.

PMID- 11324131
TI  - Research shows no fluoride-bone fracture link.

PMID- 11324132
TI  - An updated multiple language health history for dental practice.
AB  - To properly assess a patient, a variety of questions are necessary to evaluate
      signs and symptoms of medical problems and to find out about diagnosed medical
      problems and specific medical treatments, including the use of drugs or
      medications. All of these factors can have a bearing on dental management.
      Because of the diversity of the population, a variety of languages are spoken in
      California and the United States. So that dentists can communicate with those
      diverse groups, a health history form developed at the University of the Pacific
      School of Dentistry has been translated into 10 languages. The translated forms
      and the corresponding English form are presented along with an explanation and
      rationale for their use.

PMID- 11324133
TI  - Demystifying medical complexities.
AB  - Although dentists often fear treating medically complex patients, in many cases
      this fear may be based not on scientific facts but rather on a "mythology" of the
      dangers of dentistry. Dentistry is a remarkably safe profession, even for most
      medically complex patients. The myths of endocarditis, artificial joint
      infections, local anesthetics and vasoconstrictors, dental surgery in
      anticoagulated patients and patients on antiplatelet drugs, and antibiotic
      interference with oral contraceptives are discussed. Although dental treatment is
      not usually a risk factor for endocarditis, practitioners should consult the 1997
      American Heart Association statement for recommendations for endocarditis
      prevention. Most artificial joint patients should not receive antibiotic
      prophylaxis. Local anesthetics and vasoconstrictors can be used safely in most
      medically complex patients. Neither continuous anticoagulation nor antiplatelet
      medications should be withdrawn for dental surgery. Scientific studies have
      failed to document an interaction between antibiotics used in dentistry and oral
      contraceptives.

PMID- 11324134
TI  - Cardiovascular drugs and dental considerations.
AB  - This paper provides current information on the pharmacologic management of
      cardiovascular diseases. It also describes the drugs used to treat five common
      cardiovascular disorders--heart failure, coronary artery disease, atrial
      fibrillation, hypertension, and unstable angina--and lists their dental
      implications. This information can be used to monitor patients for potential
      adverse drug reactions and drug interactions and to provide an information base
      for medical consultation.

PMID- 11324135
TI  - Resources for treating patients with medically complex problems.

PMID- 11324136
TI  - Combination therapy with interferon-alpha 2b and ribavirin for the treatment of
      relapse patients and non-responders with chronic HCV infection.
AB  - BACKGROUND: Treatment of patients with chronic hepatitis C after failure of an
      interferon monotherapy remains controversial. While relapse patients have a
      sustained response after a combination therapy with interferon-alpha 2b 3 x 3
      MU/week plus ribavirin 1,000/1,200 mg daily for 24 weeks in up to 49%, the
      standard therapy for initial non-responders remains to be determined. METHODS: We
      therefore conducted a large multicenter trial to compare efficacy and safety of a
      combined interferon/ribavirin therapy in 327 non-responders and 181 relapse
      patients with chronic HCV infection outside of highly specialized institutions.
      RESULTS: After 6 months therapy with interferon-alpha-2b 3 MU thrice a week plus
      ribavirin 1,000/1,200 mg daily for 24 weeks 31% of relapse patients and 11% of
      initial non-responders achieved a sustained response according to an intent to
      treat analysis. CONCLUSIONS: These data could not confirm the high rate of
      sustained responders in relapse patients. In addition we were only able to induce
      a sustained response in every tenth non-responder. These results might reflect
      the realistic sustained response rates in a non-biased European population of HCV
      infected patients.

PMID- 11324137
TI  - Value of combinations of pancreatic function tests to predict mild or moderate
      chronic pancreatitis.
AB  - Pancreatic function tests share an insufficient accuracy concerning the detection
      of mild or moderate forms of chronic pancreatitis. It was evaluated here whether
      by combination of different assays the prediction or exclusion of chronic
      pancreatitis could be improved. METHODS: 62 patients with chronic abdominal pain
      and suspected chronic pancreatitis underwent an endoscopic retrograde
      pancreaticography. The duct alterations were classified according to the
      Cambridge criteria. In all individuals the pancreolauryl test in serum (PLT-S)
      and urine (PLT-U) was performed and elastase 1-immunoreactivity (E) as well as
      chymotrypsin (Chy) activity in stool were measured. Sensitivities, specificities,
      receiver-operator-curves as well as cut-off points at optimal accuracies were
      calculated for each single assay and all test combinations. Cut offs were
      optimized by a mathematical model to achieve highest accuracies. RESULTS: In 30
      patients the pancreatic duct was normal and in 32 patients alterations of the
      duct system were found. These were classified as mild in 10 patients, as moderate
      in 8 patients and as severe in 14 patients. In those with mild and moderate
      disease all pancreatic function tests showed sensitivities/specificities of 60
      65% and 65-70%, respectively. Only in severe chronic pancreatitis elastase was
      superior to the other tests. Combinations of function tests did not lead to
      improved accuracy. After mathematical optimization the accuracy (sensitivity 80%,
      specificity 80%) was best for the combination of PLT-S (cut off 4.7
      micrograms/ml) and E (cut off 500 micrograms/g). Both parameters had to be below
      these newly defined cut offs to diagnose chronic pancreatitis. CONCLUSIONS: The
      accuracy of pancreatic function tests may be improved by use of altered cut offs
      and a combination of serum pancreolauryl test and elastase. These newly defined
      cut offs will have to be evaluated in a much larger study.

PMID- 11324138
TI  - [Bile peritonitis in an alcoholic man after traumatic gallbladder perforation-
      differential ascitic decompensated liver cirrhosis diagnosis].
AB  - Traumatic rupture of the gallbladder is a very rare event associated with high
      mortality. Since clinical symptoms are nonspecific, diagnosis is difficult. We
      present an alcoholic with biliary ascites after traumatic perforation of the
      gallbladder. Initially, he was misdiagnosed to have ascites caused by liver
      cirrhosis. This case demonstrates, that the combination of patients history,
      clinical investigation and ultrasound allows the diagnosis of traumatic rupture
      of the gallbladder.

PMID- 11324139
TI  - [Lymphoma-simulating presentation of focal nodular hyperplasia (FNH) of the
      liver].
AB  - A 51-year-old woman, who had taken oral contraceptive drugs for 11 years, was
      referred to our Unit for examination of an asymptomatic 3.6 x 4.1 cm hypoechoic
      liver mass found by ultrasound examination carried out in the course of
      gynecological screening. INVESTIGATIONS: Laboratory evaluation revealed mild
      elevated liver enzymes. Computed tomography exhibited a hypervascularized lesion
      in segment 4 of the liver resembling a hemangioma or focal nodular hyperplasia
      but FNH was favored since magnetic resonance imaging showed a central scar within
      the hepatic lesion. Hepatobiliary scintigraphy was not typical thus an ultrasound
      guided needle biopsy was performed. Histological examination revealed lymphoma
      like infiltrates close to normal liver cells. However, the molecular biological
      examination showed oligoclonality of the infiltrating T-cells. Blood
      examinations, bone-marrow punctuation and CT thorax scan did not show any other
      lymphoma-like lesion. TREATMENT AND COURSE: After 5, 10 and 15 months the
      untreated patient was re-examined by MRI. The focal lesion showed an unchanged
      size and again a FNH-typical imaging. Liver-specific contrast enhancement was not
      suggestive for lymphoma. The lymphocytes were interpreted as an atypical lymphoid
      inflammatory infiltrate of a non-neoplastic lesion of the liver. CONCLUSIONS: The
      focal nodular hyperplasia can be a very difficult diagnosis in imaging and
      histopathological examinations. The lymphoma of the liver can be a rare but
      possible differential diagnosis.

PMID- 11324140
TI  - [Liver toxicity of drugs of plant origin].
AB  - Herbal drugs are widely used and often contain highly active pharmacological
      compounds. Recently, reports have mounted about hepatotoxicity of herbal remedies
      which ranges from mild liver enzyme alterations to chronic liver disease and
      liver failure. Hepatotoxicity of Chinese herbs has been recognized, e.g. during
      treatment of patients with atopic eczema. However, the toxic compounds remain to
      be determined. Hepatic veno-occlusive disease may result from pyrrolizidine
      alkaloids which are contained in numerous plants worldwide. Teucrium chamaedrys,
      commonly referred to as germander, may cause hepatitis and even liver cirrhosis.
      Significant hepatotoxicity has also been observed after the ingestion of
      chaparral. Recently, greater celandine, which is widely used for biliary
      disorders and dyspepsia, was identified as a cause of cholestatic hepatitis.
      Hepatotoxic reactions have also been observed after the ingestion of Atractylis
      gummifera, Callilepsis laureola, Senna, Kavapyrone and Pulegium. The aim of this
      review is to summarize potentially hepatotoxic herbal remedies, to further
      elucidate their mechanisms of toxicity and thereby underline the likelihood of
      plants to be the cause of liver damage.

PMID- 11324141
TI  - [Annual meeting of the "Study Circle for Neurogastroenterology and Motility e.V."
      5-7 March 2000--report meeting summary].

PMID- 11324142
TI  - [Evidence-based medicine--are there alternatives?].

PMID- 11324143
TI  - [Using colonoscopy in early detection of proximal neoplasia in asymptomatic
      patients].

PMID- 11324144
TI  - [Sustaining remission in Crohn disease with methotrexate--a placebo controlled
      study].

PMID- 11324145
TI  - Technique for the quantification of transient quadratic phase couplings between
      heart rate components.
AB  - A technique for the time-variant analysis of quadratic phase coupling (QPC) in
      heart rate data is introduced and tested in 6 human neonates during quiet sleep.
      The set up of the approach is based up on the assumption that QPCs in the heart
      rate variability (HRV) are related to amplitude modulation effects. The
      application of the biamplitude deals with the detection of the coupling pattern
      and the bicoherence is used for the statistical quantification of coupling. By
      means of the results of bispectral analysis the time-variant processing has been
      adapted. The frequency-selective complex demodulation of the HRV leads to the
      envelope of the respiratory sinus arrhythmia (RSA), this has been used as one
      input for a time-variant coherence analysis. The other input is the low-pass
      filtered 10-second-rhythm of the HRV. A time-continuous quantification of the
      QPC, caused by amplitude modulation (10-second-rhythm modulates the RSA), is
      possible using this approach. According to our observed results in neonatal HRV
      both a phase co-ordination between the 10-second-rhythm and RSA as well as a non
      linear coupling (amplitude modulation) between these HRV components can be seen.

PMID- 11324146
TI  - A new calibration method for 3-D position measurement in biomedical applications.
AB  - Aim of the study was to determine practicality and to test accuracy of a new
      calibration technique firstly introduced in 1998 by Schmid and Bess for
      biomechanical human tests. This technique enables three-dimensional calibration
      of camera positions as well as the calculation of internal and external camera
      parameters. It can be performed unlike other three-dimensional calibration
      techniques as the first with a planar calibration grid and only one single video
      image (of each camera) to calculate all 3-D reconstruction parameters. The tests
      were performed using two albavision ACAM G-Cameras with a resolution of 480 (h)
      by 420 (v) pixels. The achievable accuracy of distance measurements in recent
      commercially available motion measurement systems usually ranges from about 0.09%
      to 1.77% and higher. Accuracy of 0.0373% was determined with the new calibration
      technique. The 95% confidence interval ranged at +/- 0.02322 mm, the RMS (root
      mean square) error at 0.18776 mm. Better accuracy, easier and faster calibration
      are features of this new calibration technique. Required time for complete
      calibration ranged below one minute. Anticipating this new method will have good
      practicality in gait analysis or in research and industry due to increased
      accuracy and ease of use.

PMID- 11324147
TI  - [Virtual retinal display system with nodal point image of a laser beam:
      construction example and evaluation of subjective brightness perception].
AB  - We investigated the perception of brightness for red monochromatic laser light.
      For this purpose, a modified virtual retinal display (VRD) was constructed. The
      modification involved projecting the laser beam into the eye. In our VRD, the
      laser beam pivots in the nodal point of the eye (badal system). The displayed
      image therefore does not depend on the refractive state of the eye. Brightness
      perception was assessed by means of psychophysical experiments. The results of
      these experiments indicate that perception of brightness at 652 nm increases more
      rapidly with increasing physical stimulus than does the perception of white light
      (colour temperature 2'935 K). At a wavelength of 652 nm, an optical power of 79
      nW is required to produce an image subtending 2 degrees of equal brightness, as
      is perceived with an image of about 2'900 cd/m2 subtending 2 degrees.

PMID- 11324148
TI  - [Planning orthodontic surgery with the Hexapod system].
AB  - Treatment of maxillofacial dysgnathia using a combined surgical/orthodontic
      approach requires careful orthodontic and orthognathic diagnosis and treatment
      planning. In the present study, a system enabling on-line presentation of the
      necessary displacements of the jaw during surgery, while improving the accuracy
      of the planning, is described. Using the hexapod principle, it is possible to
      plan operations with six degrees of freedom and to measure the three-dimensional
      movements of jaws and jaw segments within the planning stage. Routinely prepared
      casts are employed for simulation of the operation. The displacements of the jaw
      are presented in a manner familiar to the orthodontic surgeon, namely in a
      surgical record. The accuracy achieved with the hexapod is superior to that
      achievable intra-operatively.

PMID- 11324149
TI  - [Value of exact focusing of extracorporeal shock waves (ESWT) in therapy of
      tendinitis calcarea. A prospective randomized study].
AB  - A controlled randomized study was designed to analyse the effect of
      extracorporeal shockwave therapy (ESWT) focussed on either the calcified region
      or the insertion of the supraspinatus tendon. The study included 50 patients who
      were treated with a Storz Minilith SI-1 prototype shockwave generator. In the
      treated group, 4000 impulses (ED+ 0.78 ml/mm2) were applied, under local
      anaesthesia to the insertion of the supraspinatus in 2 treatment sessions.
      Control patients received ESWT focussed on the calcified region. Follow-up
      examinations were carried out 12 weeks after treatment by an independent
      observer. We found functional improvement and pain reduction in both groups.
      Statistical analyses showed significant superiority of ESWT focussed on the
      calcified region for the parameters constant-score (primary endpoint, p < 0.001)
      and pain intensity (p = 0.001). For the treatment of calcific tendinitis
      affecting the supraspinatus, we recommend accurate fluoroscopy-controlled
      focussing of ESWT on the calcification. Focussing on the calcification rather
      than on the insertion of the supraspinatus tendon is significantly more
      effective. On the basis of our results, ESWT requires the use of suitable
      shockwave generators that permit accurate focussing.

PMID- 11324150
TI  - [New compounds for improving wear behavior of a tumor knee endoprosthesis].
AB  - Wear of the central bushing made of ultra-high molecular weight polyethylene (PE
      UHMW) of the hinged knee endoprosthesis of a tumour-resection system is the
      leading reason for revision. The aim of the study was to optimize the wear
      characteristics of the endoprosthesis on the basis of the tribological properties
      of new materials and an additional finite element (FE) calculation taking account
      of the given design. In screening tests the reference combination of PE-UHMW
      bushing and CoCr axis--used in the clinical setting--was first tested. The PE
      UHMW bushing was then replaced by one made of each of the materials reinforced
      high-density polyethylene (PE-HD) and carbon fibre-reinforced epoxy resin (CFRP).
      In addition, a new material combination with an alumina ceramic bushing and a
      CFRP axis was investigated. In comparison with the reference combination PE
      UHMW/metal, the combination of ceramic bushing and CFRP axis showed less wear.
      However, with the particular design of the prosthesis studied here, high
      mechanical loading applied experimentally resulted in mechanical failure. FE
      calculations confirmed these experimental results. Improvement of the wear
      characteristics of this specific implant caused therefore be achieved only by
      optimizing the bearing design.

PMID- 11324151
TI  - Iron chelation and related properties of Podophyllum hexandrum, a possible role
      in radioprotection.
AB  - Aqueous extract of Podophyllum species has been reported to render significant
      protection against radiation induced mortality, cytogenetic damage and cell
      death. In view of this, present study was undertaken to investigate its
      antioxidant properties. Chelation, oxidation and reduction of Fe2+ and Fe3+ were
      measured using chelating agents 2-2' bipiridyl and potassium thiocyanate
      respectively. Podophyllum extract, in a dose dependent manner, chelated Fe2+ more
      efficiently than Fe3+ and also modulated Fe2+/Fe3+ ratio. Homogenate of mouse
      liver was used to measure TBARS for estimating lipid peroxidation. Podophyllum
      extract also inhibited lipid peroxidation in a dose dependent manner and maximum
      inhibition (92%) was achieved at 1000 micrograms/ml concentration. These results
      demonstrates that Podophyllum exhibits antioxidant properties as seen through
      chelation and modulation of redox state of iron ions and these may primarily
      contribute towards its radioprotective manifestation.

PMID- 11324152
TI  - Stress induced neuron degeneration and protective effects of Semecarpus
      anacardium Linn. and Withania somnifera Dunn. in hippocampus of albino rats: an
      ultrastructural study.
AB  - Effects of herbal formulations were studied on hippocampal neuron cell bodies.
      Study was carried out in adult Swiss albino rats. Experimental rats (E) were
      divided into three groups. Group E1 rats were given immobilization stress for 14
      hr/day for 30 days. Rats in E2 and E3 group were given daily single dose (40
      mg/kg/body wt.) of alcoholic extract of S. anacardium and W. somnifera. After 1
      hr giving the plant extract, the rats were subjected to stress. Treatment
      continued for 14 hr for 30 days. Control rats were kept in complete nonstress
      condition. Ultrastructural characteristics of neuron cell bodies in hippocampal
      sublayer (CA1-CA4 and Dg) was studied in rats of E1, E2 and E3 groups and
      compared with control. Results of the present study demonstrated, that both CA2
      and Dg, 85% of neuron cell bodies exhibited degenerating characteristics, (which
      includes karyorrhexis, membrane blebbing, chromatin condensation, chromatin
      fragmentation and intracellular spacing). Interestingly, after the treatment with
      S. ancardium cells demonstrating degenerating characteristics was significantly
      reduced (80%) as compared to treatment with W. somnifera. Study suggests that
      probably both the herbal drugs have cytoprotective properties.

PMID- 11324153
TI  - Foetal amygdalar transplantation facilitates recovery of retention deficit in CeA
      lesioned rats.
AB  - Neural tissue transplant has come off age as a valuable technique for studying
      normal development and regeneration. Bilateral lesions of the central nucleus of
      amygdala (CeA) produce complete retention and acquisition deficit in inhibitory
      avoidance paradigms. The present study reports recovery of retention deficit in
      active avoidance task (AA) after amygdalar tissue transplantation in CeA lesioned
      rats. In a group of adult wistar rats, bilateral lesions of the CeA were produced
      electrolytically. In a separate group of rats foetal amygdalar tissue was
      transplanted at the CeA lesioned site 2 days after producing lesion. All the rats
      were trained on AA task before and after 5 days of lesion. In bilaterally CeA
      lesioned rats, the percentage of avoidance (% avoidance) decreased significantly
      (P < 0.05) from 85 +/- 18% prelesion to 15.5 +/- 35% postlesion. However, no
      change in the % avoidance was observed after amygdalar tissue transplantation.
      The results indicate that the transplanted rats are capable of retaining the
      learnt information in contrast to the lesion alone group of rats.

PMID- 11324154
TI  - Selenium supplementation sensitizes renca cells to tert-butylhydroperoxide
      induced loss of viability.
AB  - Mouse renal carcinoma (renca) cells growing exponentially in foetal bovine serum
      (1%) supplemented with selenium (1 microM, sodium selenite) were exposed to
      oxidative insult. It was found that glutathione peroxidase activity increased
      (44%), while the activities of catalase, glutathione disulfide reductase, and
      level of total glutathione did not change due to selenium supplementation.
      Selenium supplementation made renca cells susceptible to tert-butylhydroperoxide
      induced cell death, while it did not affect the viability when the cells were
      exposed to hydrogen peroxide. It suggested that the contribution of glutathione
      peroxidase in antioxidant defense mechanism of renca cells was possibly not
      crucial and the function of catalase might be important especially against
      hydrogen peroxide.

PMID- 11324155
TI  - Teratogenic effects of dilantin on thoraco-abdominal organs of developing chick
      embryos.
AB  - Congenital anomalies on some viscera like heart, liver and kidney have been
      investigated in chick embryos after a single injection of dilantin (3 mg/egg), a
      known antiepileptic drug, on 4th day of incubation. On 19th day of incubation,
      chick embryos were collected to observe the gross malformations and histological
      changes in heart, liver and kidney. On gross examination, visceroptosis (29%),
      thin anterior abdominal wall (28%), ectopia cordis (10%) and dextrocardia (1%)
      were observed. Histological examination of the kidney revealed glomerular
      degeneration in kidney while in liver, dilated central veins with degenerated
      hepatocytes were present. Longitudinal section of the heart showed thicker
      musculature specially of ventricles with a narrower lumen in comparison to that
      of the control. The results indicate teratogenicity of dilantin in developing
      chick embryos.

PMID- 11324156
TI  - Ascorbic acid metabolism in ageing recalcitrant sal (Shorea robusta Gaertn. f.)
      seeds.
AB  - Changes in ascorbate content and its enzymatic utilization pattern were studied
      in embryonic axes and cotyledons of sal seeds undergoing rapid loss of viability,
      at ambient conditions. Ascorbate levels were significantly higher initially in
      the embryonic axes (0.32 mg/g fresh weight) and cotyledons (0.21 mg/g fresh
      weight) of freshly mature, relatively hydrated (42.2% moisture content) and 100%
      viable sal seeds. It declined sharply as the tissues; embryonic axes and
      cotyledons, desiccated with absolutely no detectable amount in non-viable seeds
      (21% moisture content). Significantly strong correlation was obtained between
      desiccation of embryonic axes (r = 0.96) and cotyledon (r = 0.97) with loss of
      ascorbate levels and loss of germinability. Higher rates of ascorbic acid
      utilization (AAU) recorded in the embryonic axes of 100% viable seed declined
      sharply as the seed viability reduced due to desiccation below 36.8% moisture
      content. AAU was not detected in the cotyledons.

PMID- 11324157
TI  - Musa paradisiaca stem juice as a source of peroxidase and ligninperoxidase.
AB  - Musa paradisiaca stem juice has been shown to contain peroxidase activity of the
      order of 0.1 enzyme unit/ml. The Km values of this peroxidase for the substrates
      guaiacol and hydrogen peroxide are 2.4 and 0.28 mM respectively. The pH and
      temperature optima are 4.5 and 62.5 degrees C respectively. Like other
      peroxidases, it follows double displacement type mechanism. At low pH, Musa
      paradisiaca stem juice exhibits ligninperoxidase type activity. The pH optimum
      for ligninperoxidase type activity is 2.0 and the temperature optimum is 24
      degrees C. The Km values for veratryl alcohol and n-propanol are 66 and 78 microM
      respectively.

PMID- 11324158
TI  - Isolation and symbiotic characterization of aromatic amino acid auxotrophs of
      Sinorhizobium meliloti.
AB  - Ten aromatic amino acid auxotrophs of Sinorhizobium meliloti (previously called
      Rhizobium meliloti) Rmd201 were generated by random mutagenesis with transposon
      Tn5 and their symbiotic properties were studied. Normal symbiotic activity, as
      indicated by morphological features, was observed in the tryptophan synthase
      mutants and the lone tyrosine mutant. The trpE and aro mutants fixed trace
      amounts of nitrogen whereas the phe mutant was completely ineffective in nitrogen
      fixation. Histology of the nodules induced by trpE and aro mutants exhibited
      striking similarities. Each of these nodules contained an extended infection zone
      and a poorly developed nitrogen fixation zone. Transmission electron microscopic
      studies revealed that the bacteroids in the extended infection zone of these
      nodules did not show maturation tendency. A leaky mutant, which has a mutation in
      trpC, trpD, or trpF gene, was partially effective in nitrogen fixation. The
      histology of the nodules induced by this strain was like that of the nodules
      induced by the parental strain but the inoculated plants were stunted. These
      studies demonstrated the involvement of anthranilic acid and at least one more
      intermediate of tryptophan biosynthetic pathway in bacteroidal maturation and
      nitrogen fixation in S. meliloti. The alfalfa plant host seems to provide
      tryptophan and tyrosine but not phenylalanine to bacteroids in nodules.

PMID- 11324159
TI  - Anthocyanin, bisabolol and phenylammonialyase activity in cell cultures of
      Populus deltoides.
AB  - Phenolics, anthocyanin and alpha-bisabolol production from poplar (Populus
      delotides) in tissue culture was determined. A number of phenolic acids were
      identified by HPLC. PAL activity in response to phytohormones, cells growth and
      anthocyanin production showed a positive correlation. A component, alpha
      bisabolol, was identified using gas chromatography and UV spectroscopy. In vitro
      production of said metabolites was influenced by phytohormones.

PMID- 11324160
TI  - Assessment of androclonal variation in an indica rice PTB 28.
AB  - Anther culture (AC) derived 160 doubled haploid (DH) families of an indica rice
      PTB 28 were field evaluated at Port Blair (lat 11 degrees.41'13.04"N; long 92
      degrees 43'30.16"E), to assess the extent and range of induced variability among
      the androclones at segregating A2 generation and identify promising selectants
      for genetic improvement. Though the coefficient of variation (CV) for plant
      height was least (2.65%), majority of the androclones were shorter (81.7%). CV
      was high in case of panicle number per plant (24.59%) and tiller number per plant
      (28.28%), while it was maximum in respect of yield per plant (37.0%). Tiller and
      panicle number per plant registered maximum reduction compared to parent,
      however, displayed larger variations in double haploid (DH) lines. Out of 160 DH
      families, only 10 (6.3%) lines out-yielded the parent. Extreme types with wide
      variations were encountered which reaffirms the possibility of employing anther
      culture in rice improvement by restoring yield advantage in advanced generations
      or by tailoring them through recombination breeding.

PMID- 11324161
TI  - Pesticide induced alterations of non-protein nitrogenous constituents in the
      serum of a fresh water cat fish, Clarias batrachus (Linn.).
AB  - A freshwater cat fish was exposed to sublethal concentrations of two pesticides-
      carbaryl, a carbamate and phorate, an organophosphorus pesticide for 24, 72, 120
      and 168 hr. The alterations in the serum profile of non protein nitrogen
      compounds demonstrated an increase in urea, uric acid and creatinine throughout
      the experimental period.

PMID- 11324162
TI  - Magnetic resonance imaging (MRI) of Saccharum officinarum L. (sugarcane) during
      its growth for sucrose content.
AB  - Magnetic Resonance Imaging (MRI) was employed to monitor changes in image
      intensities in stems of sugarcane which reflect on the increase in sucrose
      concentration. Contrast in images originates in the increase of sucrose
      concentration in the aqueous phase of the predominant parenchyma cells and
      physiological changes. In matured stems mixed MR intensity patterns were observed
      in transverse planes. We associate this due to the reflection of vascular bundles
      in ground parenchyma cells which constitute 80% sucrose storage.

PMID- 11324163
TI  - Influence of PGRs on carbohydrate content in Lipaphis erysimi (Kalt.).
AB  - Six compounds (IBA, chlorogenic acid, cytokinine, GA3, alar B-9 and maleic
      hydrazide) belonging to four different categories of plant growth hormones were
      used to study their effect on carbohydrate content in L. erysimi. The second
      instar nymphs (48 hr old) were given both dipping and leaf surface treatment with
      1024 ppm concentration of compounds for two time intervals i.e. 48 and 96 hr. The
      carbohydrate content decreased after treatment with 4 of the plant growth
      regulators i.e. GA3, alar B-9, IBA and chlorogenic acid with maximum suppression
      in GA3 treatment. Cytokinine did not induce any derogatory influence on
      carbohydrate content. The treatment with maleic hydrazide, on the other hand
      enhanced the carbohydrate content. It could be concluded that the application of
      these PGRs affected the carbohydrate synthesis or metabolism.

PMID- 11324164
TI  - Somatic embryogenesis from leaf derived callus of Tylophora indica (Burm. f.)
      Merrill.
AB  - Mature leaf explant derived callus of Tylophora indica (Burm. f.) Merrill yielded
      somatic embryos on MS medium supplied with BA(1-2 mg/L) or kinetin(1-5 mg/L) or
      kinetin/BA (1-2 mg/L) used along with IAA(0.1-1 mg/L). Maximum somatic embryos
      (30) could be recovered from 100 mg of embryogenic callus within 60 days at an
      optimum concentration of 2 mg/L of BA which was also best suited for providing
      the maximum conversion rate (90%) of embryoids to plantlets. Kinetin (1-5 mg/L),
      used as the sole growth hormone, induced the development of embryoids showing
      either shoot or root primordia in 30% of the cultures. However, embryoids with
      shoot primordia developed roots upon transfer to medium containing IAA(0.1 mg/L)
      and kinetin(2 mg/L). Embryoids from all cultures germinated in the initiation
      medium and were transplanted to sterile vermiculite for hardening. After two
      weeks of hardening, the plantlets were transferred to the green house where they
      grew and established well showing a high rate of survival (90%).

PMID- 11324165
TI  - Direct somatic embryogenesis and plantlet regeneration from leaf explants of
      niger, Guizotia abyssinica (L.f.) Cass.
AB  - Somatic embryogenesis was induced in niger (Guizotia abyssinica (L.f.) Cass.)
      using a simple one step method. Leaf explants were cultured on MS medium with 2,4
      D and BAP/Kn individually and in combination. Somatic embryogenesis occurred
      directly without an intervening callus proliferation phase from subepidermal
      regions of leaf explants on MS medium supplemented with 2,4-D (2.0 and 5.0
      microM) plus Kn/BAP (1.0 and 2.0 microM). Regenerated somatic embryos were
      successfully grown into whole plants.

PMID- 11324166
TI  - Photosynthetic acclimation to rising atmospheric carbon dioxide concentration.
AB  - With rising level of CO2 in the atmosphere plants are expected to be exposed to
      higher concentration of CO2. Since, CO2 is a substrate limiting photosynthesis
      particularly in C3 plants in the present atmosphere, the impact of elevated CO2
      would depend mainly on how photosynthesis acclimates or adjusts to the long term
      elevated level of CO2. Photosynthetic acclimation is a change in photosynthetic
      efficiency of leaves due to long term exposure to elevated CO2. This change in
      photosynthetic efficiency could be a biochemical adjustment that may improve the
      overall performance of a plant in a high CO2 environment or it could be due to
      metabolic compulsions as a result of physiological dysfunction. Acclimation has
      generally become synonymous with the word response, if long term exposure to
      elevated CO2 decreases the photosynthesis rate (Pn) at a given CO2 level, it is
      called negative acclimation, if it stimulates Pn at a given CO2 level, it is
      called positive acclimation. Photosynthetic acclimation is clearly revealed by
      comparing Pn of ambient and elevated CO2 grown plants at same level of CO2.
      Species level differences in acclimation to elevated CO2 have been reported. The
      physiological basis of differential photosynthetic acclimation to elevated CO2 is
      discussed in relation to the regulation of photosynthesis and photosynthetic
      carbon partitioning at cellular level.

PMID- 11324167
TI  - Cyclic AMP-mediated control of oocyte maturation in the catfish, Clarias
      batrachus (Bloch): effects of 17 alpha,20 beta-dihydroxy-4-pregnen-3-one and
      phosphodiesterase inhibitors.
AB  - An increase in the percentage of germinal vesicle breakdown (GVBD) with a
      corresponding decrease in cAMP was found in the oocytes which were incubated for
      36 hr with different concentrations of 17 alpha,20 beta-dihydroxy-4-pregnen-3-one
      (17 alpha,20 beta-DP). At its highest concentration (1 microgram/ml), 17 alpha,20
      beta-DP induced 91.9 +/- 2.3% GVBD and decreased cAMP level to 0.8 +/- 0.1
      pmol/oocyte from 2.9 +/- 0.2 pmol/oocyte (control). The two different known
      inhibitors of phosphodiesterase viz. 3-isobutyl-1-methyl-xanthine (IBMX) and
      theophylline inhibited GVBD in vitro and promoted the accumulation of cAMP in a
      dose-dependent manner irrespective of whether the oocytes were treated for a
      short duration (2 hr) or for a long duration (36 hr). Evaluation of time course
      response to 1 mM IBMX or 1 mM theophylline revealed that cAMP levels increased at
      all the time points when compared with their respective controls and blocked
      maturation. In contrast, 1 microgram/ml 17 alpha,20 beta-DP not only induced
      oocyte maturation but also caused an immediate decrease in cAMP within the first
      2 hr (from 3.2 +/- 1.3 to 1.3 +/- 0.1 pmol/oocyte) of incubation which was
      maintained till the end of experiment (36 hr). Likewise, a significant inhibition
      of GVBD and accumulation of cAMP was recorded even in oocytes pre-stimulated with
      1 microgram/ml 17 alpha,20 beta-DP for 6 hr and then treated with different
      concentrations of IBMX or theophylline. Taken together, these data strongly
      suggest that in C. batrachus a decrease of oocyte cAMP concentration is a
      prerequisite for the induction of oocyte maturation, and its increase is
      associated with the maintenance of meiotic arrest.

PMID- 11324168
TI  - Profile of organ weights and plasma concentrations of melatonin, estradiol and
      progesterone during gestation and post-parturition periods in female Indian palm
      squirrel Funambulus pennanti.
AB  - Todate, report about the role of pineal gland in maintaining the normal
      physiology of gestation is scanty. Present study is the first of its kind giving
      a detail profile of organ weights and plasma concentration of melatonin,
      estradiol and progesterone to suggest a possible role of pineal gland in
      maintaining normal physiology during gestation and post-parturition periods of
      female Indian palm squirrel F. pennanti. Inspite of, inverse pineal
      gonadal/melatonin-steroids interrelationship in adult (non-pregnant) females, the
      present results study suggest a direct relationship of pineal gland activity with
      ovarian steroids especially during the gestation period. The inverse relationship
      of melatonin and ovarian steroids is again established after parturition and
      maintained throughout the life. Thus the pineal gland (activity as judged by its
      weight, biochemical contents i.e. protein and cholesterol and plasma melatonin
      level) maintained ovarian/uterine physiology and regulated plasma concentrations
      of estradiol and progesterone during gestation and post-parturition periods. It
      is suggested that the pineal gland and its hormone melatonin play an important
      role to maintain the normal physiology of gestation and the post-partum recovery
      in Indian palm squirrel F. pennanti.

PMID- 11324169
TI  - Effect of actinomycin D and cycloheximide on ischemic preconditioning-induced
      delayed cardioprotective effect in rats.
AB  - The present study was designed to investigate the effect of actinomycin D, a
      transcription inhibitor, and cycloheximide, a translation inhibitor, on the
      delayed cardioprotective effect of ischemic preconditioning. Left thoracotomy was
      performed in anaesthetized rats at 4th/5th intercostal space and polypropylene
      suture (5-0) was employed to occlude left common coronary artery. Ischemic
      preconditioning was produced by four episodes of 5 min of coronary artery
      occlusion followed by 5 min of reperfusion and thoracic cavity was sutured. Left
      thoracotomy was performed again after 24 hr of ischemic preconditioning and left
      coronary artery was occluded for 30 min followed by reperfusion for 120 min. Area
      at risk and infarct size was estimated by patent blue and TTC staining
      respectively. Total left ventricular RNA was isolated and estimated
      quantitatively. Ischemic preconditioning, 24 hr after its induction, produced
      significant decrease in myocardial infarct size occurred as a result of sustained
      ischemia and reperfusion but produced no marked effect on ventricular RNA
      content. Actinomycin D and cycloheximide only, in high dose, markedly attenuated
      ischemic preconditioning induced decrease in myocardial infarct size. However, no
      such effect was noted with low dose of cycloheximide. The results suggest that
      delayed cardioprotective effect of ischemic preconditioning may be mediated
      through denovo synthesis of protein(s) which is regulated both at transcriptional
      and translational level.

PMID- 11324170
TI  - Modulation of motor functions involving central dopaminergic system by L
      histidine.
AB  - There exists a possibility of interactions of histaminergic system with other
      neurotransmitters and their receptors in the central nervous system. Experimental
      evidences suggest a possible inhibitory influence of histaminergic system on the
      dopaminergic system. To elucidate the possible interaction between the
      histaminergic and dopaminergic pathways, we devised a strategy to study their
      effects on locomotor function and stereotypy behaviour. We investigated the
      effect of L-histidine, the precursor of histamine, on apomorphine-induced
      stereotypy and perphenazine-induced catalepsy. Histidine antagonised apomorphine
      induced stereotypy. This inhibitory effect of histidine was abolished by both H1-
      and H2-receptor antagonists, chlorpheniramine and cimetidine, respectively.
      Perphenazine-induced catalepsy was potentiated by histidine and this effect was
      inhibited by chlorpheniramine alone but not by cimetidine. These results confirm
      a possible histamine-dopamine interaction in the modulation of motor functions by
      the central nervous system.

PMID- 11324171
TI  - Effect of Piper longum Linn, Zingiber officianalis Linn and Ferula species on
      gastric ulceration and secretion in rats.
AB  - Use of Dipaniya Mahakasaya, a group consisting of 10 herbal drugs, has been
      suggested in Charaka Samhita to improve digestion. Out of these 10 plants, three,
      viz. P. longum (water decoction), Z. officianalis (water decoction) and Ferula
      species (colloidal solution) were studied for their antiulcer and mechanism of
      antiulcer effects in rats. All the drugs in the dose of 50 mg/kg, p.o., 60 min
      prior to experiment, showed significant protection against gastric ulcers induced
      by 2 hr cold restraint stress, aspirin (200 mg/kg, 4 hr) and 4 hr pylorus
      ligation. The antiulcerogenic effect seemed to be due to the augmentation of
      mucin secretion and decreased cell shedding rather than offensive acid and pepsin
      secretion which however, were found to be increased by them.

PMID- 11324172
TI  - Effect of herbal preparation, brahma rasayana, in amelioration of radiation
      induced damage.
AB  - Oral administration of brahma rasayana (BR; 10 and 50 mg/dose/animal) for 15 days
      increased significantly total leukocyte count and percentage of polymorphonuclear
      cells in irradiated mice. Bone marrow cellularity and alpha-esterase positive
      cells also increased significantly in radiation-treated animals after BR
      administration. Number of nodular colonies on the surface of spleen on day seven
      increased significantly in lethally irradiated recipients receiving bone marrow
      cells from animals treated with BR. Oral administration of BR also enhanced in
      serum level of interferon-gamma (IFN-gamma), interleukin-2 (IL-2), and
      granulocyte macrophage-colony stimulating factor(GM-CSF) in normal and irradiated
      mice. These results indicated that proliferation of stem cells induced by BR in
      irradiated mice may be related to its stimulation of cytokine production.

PMID- 11324173
TI  - Spirituality, meaning, mental health, and nursing.
AB  - 1. Spirituality, defined as meaning making, is a primary motivation in life. 2.
      The medical literature increasingly demonstrates an important positive
      relationship between spirituality and health. 3. Nurses often feel uncomfortable
      or unprepared to discuss spiritual issues with patients. 4. Through a few simple
      questions, nurses can easily make spiritual assessment a routine part of taking a
      patient's psychosocial history.

PMID- 11324174
TI  - Recovery at your own PACE (Personal Assistance in Community existence).
AB  - 1. People can recover fully from even the most severe forms of mental illness. 2.
      The Empowerment Model of Recovery describes the dynamics of recovery and
      prevention of mental illness. 3. PACE (personal assistance in community
      existence) is the application of the recovery principles.

PMID- 11324175
TI  - Vitamins, herbs, and supplements: tools of empowerment.
AB  - 1. Consumers who elect to use natural products are electing to do more than
      simply use a product. Their choice is an act of self-empowerment. 2. Education is
      necessary because these products most often are not being obtained in a
      professional, consultative setting but rather in chain discount department stores
      and supermarkets. 3. If consumers choose to address their health concerns using a
      natural-based treatment plan, consultation with a health care practitioner who
      shares this shift in perspective and who follows the literature is important. 4.
      A paradigm shift could be on the health care horizon, which when complete would
      make herbs and other natural products part of mainstream health care practice.

PMID- 11324176
TI  - Reiki. A complementary therapy for nursing practice.
AB  - 1. Reiki is an ancient healing art involving the gentle laying on of hands. It
      can be practiced anytime and anywhere. 2. Reiki can be used as a complementary
      treatment to medical protocols. 3. Hand positions customarily correspond to the
      body's endocrine and lymphatic systems and major organs, focusing on seven main
      chakras. 4. More research investigating the effects of Reiki on persons with
      psychiatric and medical disorders is necessary.

PMID- 11324177
TI  - Reclaiming our healing role through integrative care.

PMID- 11324178
TI  - A troubling triangle: an exploration of loneliness, helplessness, and boredom of
      residents of a veterans home.

PMID- 11324179
TI  - Demoralization syndrome--a relevant psychiatric diagnosis for palliative care.
AB  - Hopelessness, loss of meaning, and existential distress are proposed as the core
      features of the diagnostic category of demoralization syndrome. This syndrome can
      be differentiated from depression and is recognizable in palliative care
      settings. It is associated with chronic medical illness, disability, bodily
      disfigurement, fear of loss of dignity, social isolation, and--where there is a
      subjective sense of incompetence--feelings of greater dependency on others or the
      perception of being a burden. Because of the sense of impotence or helplessness,
      those with the syndrome predictably progress to a desire to die or to commit
      suicide. A treatment approach is described which has the potential to alleviate
      the distress caused by this syndrome. Overall, demoralization syndrome has
      satisfactory face, descriptive, predictive, construct, and divergent validity,
      suggesting its utility as a diagnostic category in palliative care.

PMID- 11324180
TI  - Within the Circle of Care: patient experiences of receiving palliative care.
AB  - This paper presents an overview of a qualitative study of six recently discharged
      hospice patients, who had experienced at least two episodes of inpatient
      palliative care and who were interviewed about their experience of care. The
      resulting data formed a representation--the Circle of Care--with a central theme
      being the recognition of patient identity. Other emerging themes were: humour,
      being watched, caring manner, being safe, chosen isolation, relinquishment and
      relaxation, keeping control, awareness of mortality, recognition of the
      palliative care philosophy, and the effect of the aesthetic and spiritual
      environment.

PMID- 11324181
TI  - When grief faces down chance.

PMID- 11324182
TI  - The emotions and coping strategies of caregivers of family members with a
      terminal cancer.
AB  - This study documents the emotional experiences and coping strategies of a group
      of caregivers as they move from the diagnosis of a close family member with
      terminal cancer through the stages of caring and post bereavement. Supportive
      evidence, matching that of previous literature, was gathered regarding the impact
      of such care, but additional findings counter the notion of "burden" by revealing
      that strong positive emotions were experienced by these caregivers regarding the
      opportunity given to them to express their love through care. By contrast and
      post bereavement, however, intense grief was reported. There appeared to be a
      complete lack of emotional support throughout from health professionals,
      particularly in the bereavement phase when need is very apparent.

PMID- 11324183
TI  - Pattern of drug use by advanced cancer patients followed at home.
AB  - The aim of this study was to document the drugs most commonly prescribed to
      control symptoms in advanced cancer patients being followed at home. We analyzed
      data for 128 patients admitted to a home palliative care program from January
      1993 to January 1995. All patients were followed at home until death by a team
      consisting of doctors and nurses, and were given two or three medical
      examinations a week. The most frequently prescribed drugs were analgesics and
      drugs commonly used to prevent NSAID-induced gastric toxicity. Slow-release
      morphine was the analgesic used most often. Most patients received more than four
      drugs. Younger people received morphine more often than did older patients.
      CONCLUSIONS: Drug monitoring is a useful audit tool for verifying the quality and
      quantity of drugs prescribed for advanced cancer patients being followed at home.
      Pharmacological usage should be reviewed periodically and should reflect evidence
      based practice.

PMID- 11324184
TI  - Palliative care on the net: an online survey of health care professionals.
AB  - A survey was conducted to explore Internet use by palliative care health
      professionals (HCP). The survey was placed on the World Wide Web with an
      underlying database, and palliative care HCP were invited to participate via a
      palliative-care-related website, listserv, and newsletter. A total of 417
      evaluable responses were received over a four-month period. Of these, 36%
      indicated they were from physicians and 30% from nurses, a third of respondents
      were practicing palliative care full time. Although 63% of respondents were from
      North America, regions from all over the world were represented. Eighty-eight
      percent of respondents were searching the Internet for clinical information, 80%
      were using email, 69% were accessing online medical journals, and 59% were
      subscribers to a palliative-care-related listserv or newsgroup. This survey
      illustrates the global outreach of the Internet and draws attention to the
      growing interest in the use of the Internet for education, research, and clinical
      use. Further development of online resources should address the needs of users.
      Evaluation of these resources is called for.

PMID- 11324185
TI  - Computerized quality-of-life screening in a cancer pain clinic.
AB  - METHODS: To determine the utility and acceptability to patients and staff of a
      computerized quality-of-life (QOL) screening program in a tertiary ambulatory
      cancer pain clinic, patients were administered the computerized EORTC-QLQ-C30
      questionnaire. A report summarizing this QOL information was given to clinic
      staff prior to each patient's appointment. Both the patient and the clinical
      staff were surveyed afterwards. RESULTS: Although more than half of the 46
      patients had never used a computer before, almost all reported that the program
      was easy to use and understand, enjoyable, helpful, and quick. Their attitudes
      toward computers significantly improved from pre- to post-assessment. Staff found
      the QOL information to be appropriate and useful. CONCLUSIONS: The computerized
      questionnaire was readily used by patients and was helpful to pain clinic staff,
      making it an appropriate tool for identifying important QOL problems and issues
      in busy clinical settings, even for inexperienced computer users with significant
      functional impairment.

PMID- 11324186
TI  - The Edmonton Functional Assessment Tool: further development and validation for
      use in palliative care.
AB  - The objective of this study was to examine the validity of the revised version of
      the Edmonton Functional Assessment Tool (EFAT-2), which was designed to measure
      physical impairment and functional performance of patients in palliative care.
      The EFAT-2 was administered to 275 patients on admission to an acute palliative
      care unit. Principal-components factor analysis was performed on the 10 items of
      the scale, and Cronbach's alpha was calculated to measure internal consistency. A
      one-way analysis of variance (ANOVA) was carried out to compare the admission
      EFAT-2 scores of three groups of patients: (a) deceased on the unit, (b)
      transferred to a continuing care palliative unit, (c) discharged home. Two main
      factors were revealed: physical and non-physical (cognitive/affective). Pain was
      identified as an independent item and did not correlate with any other item.
      Cronbach's alpha was 0.86. The ANOVA was significant (F [2,267] 29.063, p <
      0.001). The results suggest that the EFAT-2 measures one construct. They also
      suggest that the EFAT-2 is able to discriminate between palliative care patients
      based on discharge location.

PMID- 11324187
TI  - Cancer self-help groups are here to stay: issues and challenges for health
      professionals.

PMID- 11324188
TI  - Hepatocarcinoma with concomitant paraneoplastic encephalomyelitis.

PMID- 11324189
TI  - Infant botulism: case reports and review.
AB  - Infant Botulism (IB) is a relatively uncommon, though potentially life
      threatening neuroparalytic illness caused by the toxins elaborated by Clostridium
      botulinum (C botulinum). We describe two cases of Infant Botulism. Both these
      infants presented with a sepsis-like picture and were unsuspectingly treated with
      the conventional antibiotics ampicillin and gentamicin. The neuroparalytic
      syndrome of both infants was probably potentiated by the use of gentamicin. We
      suggest that cefotaxime be carefully considered instead of gentamicin in the
      initial management of infants presenting with a sepsis-like clinical picture and
      associated history of constipation, recent onset of hypotonia, poor feeding
      and/or drooling. Clinical trials evaluating human Botulism Immune Globulin (BIG)
      are under way by the California Department of Health. This article comes at a
      very timely moment because once FDA approved, BIG will be the only specific
      treatment available for this illness.

PMID- 11324190
TI  - Five-year experience with an early discharge program in well newborns.
AB  - PURPOSE: This study was conducted to determine if early postnatal discharge (< or
      = 48 hrs; EDC) 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 hrs after birth (LDC). METHODS: This was a retrospective medical
      chart review. Infants who were born at Norton Hospital in Louisville, Kentucky,
      between 1/1/94 and 12/31/98, discharged as well newborns and treated at Kosair
      Children's Hospital, Louisville, Kentucky, within 7 days of neonatal discharge,
      were eligible for review. 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 rates for LDC infants when compared to EDC infants. When
      considering jaundice alone as an admitting diagnosis, EDC infants were admitted
      at a rate 4 times that of LDC infants and with higher serum bilirubin
      concentrations. Jaundiced infants were almost uniformly breast-fed. CONCLUSIONS:
      Overall, early discharge of well newborns appears to be a safe and reasonable
      practice. However, the risk for severe jaundice is an unresolved issue which
      requires a discharge strategy and early follow-up to prevent serious morbidity.
      Early discharge should not be implemented without a mechanism for early follow-up
      within 48 hours of discharge.

PMID- 11324191
TI  - Abused drugs.

PMID- 11324192
TI  - Reducing the use of restraints.

PMID- 11324193
TI  - Pain and principles of effective analgesic use for dental pain control.
AB  - Patients have the right to expect effective pain control and relief following
      dental treatment. In recent years, clinical guidelines on pain control have been
      published and disseminated. This article reviews current concepts of pain and
      principles of effective pharmacologic pain control. This material was presented
      as part of the 57th Tennessee Dental Association Postgraduate Dental Seminar.

PMID- 11324194
TI  - Oral exfoliative cytology procedures: conventional, brush biopsy and ThinPrep.

PMID- 11324195
TI  - Apical root resorption in patients treated with comprehensive orthodontics.
AB  - External apical root resorption (EARR) is a common--but seldom extreme-
      consequence of orthodontic treatment. Incisors are most at risk, perhaps because
      of their single roots and because they typically are moved farther than other
      teeth. We followed a cohort of patients (n = 153) treated with comprehensive
      orthodontics. EARR was scored on the upper incisors with a qualitative five-grade
      ordinal scale. There was no EARR at the start of treatment, but most (> 80%)
      exhibited slight-to-moderate EARR by the end of treatment (i.e., a loss of 1-2
      mm). Cases treated with premolar extractions experienced more EARR because their
      incisors were retracted farther; however, the sum of the effects of patients' sex
      and age, and severity of the malocclusion, and the kind of mechanics used
      accounts for little of the overall variation in EARR. Instead, it appears that
      genetically-based inter-individual variation in susceptibility to EARR is the
      most influential factor. Research should be directed at understanding the
      biochemical nature of susceptibility so prospective patients can be screened to
      identify those at particular risk.

PMID- 11324196
TI  - Erythromycin and amoxicillin?

PMID- 11324197
TI  - A look at the future of dentistry in Tennessee.

PMID- 11324198
TI  - Conservative management of malocclusion in mixed dentition.
AB  - The treatment planning in mixed dentition period has changed from extraction to
      non extraction. Any orthodontic treatment must take into consideration the growth
      trends and the pubertal growth spurt. The two cases presented here were treated
      during mixed dentition period in different ways: one with fixed appliances and
      the other with removable myofunctional appliance therapy, with satisfactory
      results. Hence for a conservative treatment approach, the non-extraction
      treatment is recommended in mixed dentition period.

PMID- 11324199
TI  - Reattachment of a fractured non-vital central incisor fragment: a case report.
AB  - Reattachment of the original tooth fragment to the fractured tooth provides
      benefits of maintaining the tooth's shape, colour texture and translucency in the
      restoration. This paper describes fragment reattachment of a non-vital central
      incisor five months after trauma.

PMID- 11324200
TI  - Unusual presentation of mandibular extraoral sinus in a fourteen year old girl: a
      case report.
AB  - A case of fourteen year old healthy girl with complaint of a discharging sinus on
      the lower right side of face is reported. All teeth were vital and there was no
      evidence of periodontitis. There was no history of extraction of a tooth. Total
      leucocyte count, differential leucocyte count, fasting blood sugar, chest x-ray
      and routine urine examination were within normal limits. Actinomycosis and
      scrofuloderma which simulate such a condition were ruled out by culture study.
      The intraoral periapical x-ray of mandibular molar showed questionable periapical
      changes at the time of presentation. But definite osteolysis was observed in the
      repeat radiograph after three months. It was decided to extract the second molar
      and curette the sinus tract. The extraction proved to be difficult. On
      examination of the extracted tooth, it was found that the mandibular second molar
      and second premolar were fused together. The radiograph of the tooth taken after
      extraction showed confluence of the premolar pulp with the periodontal membrane.
      On follow up, the lesion was found to heal satisfactorily.

PMID- 11324201
TI  - Effect of dental health education on the oral health status of a rural child
      population by involving target groups.
AB  - India, a developing country faces many challenges in rendering oral health needs.
      The majority of Indian population resides in rural areas, of which more than 40%
      constitute children. These children cannot avail dental facilities due to
      inaccessibility, financial constraints and stagnation of public dental healthcare
      services. This entails the health professional to adopt a more practical approach
      to achieve primary prevention of oral diseases. The most viable solution seems to
      be dental health education. Documented evidence shows that teachers and parents
      can augment dental health behaviour. With this background, it was decided to
      target children in a rural area for comparing the effect of education on children
      alone, children coupled with teachers and children with the involvement of their
      parents. An interventional study of 4 months duration was conducted on 430
      children, 7 teachers and 100 parents. The parents were educated at home. Clinical
      oral health status was assessed prior to the delivery of dental health education
      and also following the intervention. Results showed that the dental health scores
      improved best in the group of children involving the teachers. It was concluded
      that teachers could be targeted in order to enhance the effect of dental health
      education campaigns on children.

PMID- 11324202
TI  - Bilateral Tessier no. 4 facial cleft with left eye anophthalmos: a case report.
AB  - Craniofacial clefts are very rare and manifest in a variety of patterns. Tessier
      classified these clefts in 1973 and numbered them 0 to 14. Tessier No. 4 Facial
      cleft is a rare variant of craniofacial cleft. Not more than 50 cases are
      reported in world literature, amongst which only 5 cases are true bilateral in
      nature. However, combinations of two different variants are not very uncommon. A
      case of male Indian child aged 4 years with a true bilateral Tessier No. 4 Facial
      cleft is reported. He also had anophthalmos of the left eye. This is probably the
      first case in which true bilateral Tessier No. 4 Facial cleft with anophthalmos
      of one eye is noticed.

PMID- 11324203
TI  - Changes in developing succedaneous teeth as a consequence of infected deciduous
      molars.
AB  - The need for dental treatment in paediatric dental patients is immense. The
      present study was carried out in fifty children in the age group of five to ten
      years of age with recurrent episodes of dentoalveolar infection. Advanced pulpal
      infections led to torsion in 54 percent, premature eruption in 46 percent, crater
      like bone loss in 36 percent, sequestration and dilaceration in 10 percent and 6
      percent respectively. Most of the developmental disturbances could have been
      avoided with timely antibiotics and endodontic intervention.

PMID- 11324204
TI  - Selected cephalometric norms in south Kanara children.
AB  - Cephalometric Norms from forty South Kanara children were selected and it was
      found that these children have a tendency towards class II skeletal relation.
      Females showed a protrusive Maxillary and Mandibular base. Certain new landmarks
      were also introduced, the value of which gives the molar relationship. Length of
      Maxillary and Mandibular bases were also standardised for class I cases.

PMID- 11324205
TI  - Wavelength-dependent roughness: a quantitative approach to characterizing the
      topography of rough titanium surfaces.
AB  - Topographies of grit-blasted, etched, grit-blasted and etched, and
      microfabricated and etched surfaces of commercially pure titanium have been
      investigated. Such surface topographies vary across the scale range of interest
      for dental implants, extending from nanometers to millimeters. The complete
      characterization of topography requires the use of complementary methods. This
      study compared the topographic characterization methods of non-contact laser
      profilometry, interference microscopy, stereo-scanning electron microscopy
      (stereo-SEM), and atomic force microscopy. Non-contact laser profilometry was
      shown to be a useful method to characterize topographic features in the micron to
      millimeter range, whereas interference microscopy and stereo-SEM can be employed
      down to the submicron range. Stereo-SEM is particularly useful for quantifying
      topographies with complex, strongly corrugated ("sharp"), and high-aspect-ratio
      features and was shown to be complementary to non-contact laser profilometry and
      interference microscopy. Because of tip-related envelope problems, atomic force
      microscopy was not found to be suitable for the type of surfaces investigated in
      this study. Independent of the method used, the commonly used "integral"
      amplitude roughness parameters, such as Ra, Rq, or Rt, were often of limited
      value in the description of actual implant surfaces. The application of the
      wavelength-dependent roughness approach was shown to be an effective method for
      the description of surface topographies in the complete range of characteristic
      roughness and is also a useful means of examining the effects of surface
      treatment processes.

PMID- 11324206
TI  - A multicenter 12-month evaluation of single-tooth implants restored 3 weeks after
      1-stage surgery.
AB  - The time-intensive, multi-step process of dental implant therapy limits patient
      acceptance. This 3-year prospective multicenter study sought to determine the
      safety of an expedited therapy that consisted of loading unsplinted maxillary
      anterior single-tooth implants 3 weeks after 1-stage surgical placement, and
      determination of the peri-implant cortical bone and mucosal responses to the
      expedited procedure. Fifty-two patients missing 1 or 2 maxilliary anterior teeth
      were enrolled in a study approved by the Institutional Committee on Human
      Subjects Research and based on strict inclusion and exclusion criteria. Astra
      Tech ST implants placed in a 1-stage procedure were restored 3 weeks later with
      ST abutments and a provisional crown (baseline); 7 to 9 weeks later, a porcelain
      fused-to-metal or all-ceramic crown was cemented. Radiographic and clinical
      examinations were made at baseline and at 6 and 12 months. Implant survival was
      recorded. Cortical bone responses and peri-implant mucosal responses were
      evaluated. Fifty-eight implants were placed. During the 3-week period after
      implant placement, 4 patients were dismissed because of smoking cigarettes (a
      protocol deviation), and 1 patient was excluded because of deviation in loading
      time. Of the remaining 53 implants, 2 failed before definitive crown cementation.
      The resultant 96.2% survival rate was independent of implant length, tooth
      position, and bone quality/quantity. The mean change in marginal bone level was
      0.4 mm at 12 months. The number of surfaces with plaque decreased from 3.4% at
      baseline to 0.5% at 12 months. The surfaces with inflammation also decreased. A
      mean gain in papilla length of 0.61 mm occurred, and a gain in buccal gingiva (x
      = 0.34 mm) was observed. A high success rate with positive tissue responses was
      achieved for maxillary anterior unsplinted single-tooth implants placed in a 1
      stage surgery and restored at 3 weeks. This 2-component system is suited to a
      single-stage, rapid loading protocol for esthetic single-tooth replacement.

PMID- 11324207
TI  - A prospective multicenter clinical study of the Osseotite implant: four-year
      interim report.
AB  - This article reports the 4-year interim results of a multicenter study evaluating
      the clinical performance of the Osseotite dental implant. At 4 study centers, 485
      Osseotite implants were consecutively placed in 181 patients (219 were placed in
      the mandible and 266 in the maxilla). A total of 355 implants were placed in
      posterior regions. Short implants (10 mm or less) represented 31.5% (n = 153) of
      all implants placed in this study. Patients were restored with 210 restorations,
      distributed as 123 short-span prostheses, 58 single-tooth replacements, 28 long
      span prostheses, and 1 maxillary overdenture. At this 4-year interim evaluation,
      the mean time from implant placement to the most recent evaluation was 52.6 +/-
      3.0 months, with a mean loading time of 43.3 +/- 3.8 months. Of the 485 implants
      placed, there have been 6 failures. All implant failures occurred prior to
      loading and were categorized as early implant failures. Five of the 6 failures
      occurred in the maxilla. Only one of the 153 short implants failed to integrate.
      Baseline radiographs were obtained at prosthesis connection. Radiographic
      analysis 1 year post-restoration showed a mean bone loss of 0.09 +/- 0.7 mm. From
      baseline to the end of the second year of function, an overall mean bone loss of
      0.13 +/- 0.8 mm was recorded, indicating no additional bone was lost after the
      first year of implant function. At 4 years, the cumulative implant success rate
      for all implants placed in this study was 98.7%, with a 99.4% success rate in the
      posterior mandible and 98.4% success rate in the posterior maxilla. Results of
      this 4-year interim analysis indicate that this implant achieved a high success
      rate in posterior regions and that all failures with this implant in this patient
      population occurred prior to implant loading. When the clinical success of
      implants 10 mm or shorter was compared to that of implants greater than 10 mm in
      length, the shorter implants in this study performed similarly to longer
      implants.

PMID- 11324208
TI  - Early implant failures in patients treated with Branemark System titanium dental
      implants: a retrospective study.
AB  - Implant failure has been associated with factors such as poor bone quality,
      insufficient bone volume, implant instability, unfavorable implant loading, and
      smoking habits. Infections and host responses may also be important factors in
      dental implant failure. The objectives of the present study were to identify
      various explanatory factors associated with titanium implant failure. Forty
      subjects with stage 1 non-osseointegrated titanium dental implants (NOTI) ad
      modum Branemark and 40 age- and gender-matched control subjects with successfully
      osseointegrated titanium implants (SOTI) were studied. Clinical data and gamma G
      immunoglobulin (IgG) antibody titers were studied. An independent t test revealed
      that significantly longer implants were placed in subjects with SOTI (P < .05).
      Statistically significant differences in bone shape and resorption (BSR) scores
      were found between SOTI and NOTI (P < .05). Logistic regression analysis
      identified 3 significant explanatory outcome variables: serum antibody avidity
      scores for Bacteroides forsythus (P < .0001), serum antibody titers to
      Staphylococcus aureus (P < .001), and the BSR scores (P < .05). Antibody avidity
      to B forsythus and antibody titer to S aureus were therefore the 2 most important
      factors associated with early implant failures and with a significant predictive
      ability. This indicates that immunologic factors are involved in
      osseointegration.

PMID- 11324209
TI  - Early experience with Wide-Platform Mk II implants. Part I: Implant survival.
      Part II: Evaluation of risk factors involving implant survival.
AB  - Part I of this study describes the survival of a wide-platform, wide-diameter
      implant (Wide-Platform Mk II). Beginning in January 1997, 85 Wide-Platform Mk II
      implants were placed in the jaws of 63 patients (35 males and 28 females). Male
      patients experienced 10 implant failures, and female patients lost 9 implants.
      The mean time of implant follow-up was 286 days (median, 280), with a maximum of
      734 days and a minimum of 0 days. Implant loss was 19% in the mandible and 29% in
      the maxilla. Kaplan-Meier analysis showed a probability of implant failure after
      1 year of 0.649 (confidence interval, 0.455 to 0.926) in the maxilla and of 0.751
      (confidence interval, 0.616 to 0.915) in the mandible. No apparent relationship
      was noted between implant survival and implant length. Part II of this study
      evaluated the association between the survival of a new implant design and a
      number of potential risk factors. A retrospective chart review was conducted for
      all patients who received Wide-Platform Mk II implants and who agreed to allow a
      medical records review for research purposes. Kaplan-Meier survival curves were
      used to assess the probability of implant survival relative to time. The
      relationships between implant survival and implant location, history of tobacco
      use, current tobacco use, sinus grafting, bruxism, and root canal therapy were
      assessed by Cox proportional hazards modeling. Although the hazard ratio showed
      an increased risk of implant failure with some factors, particularly a history of
      root canal therapy in the site of implant placement (hazard ratio 3.2, P = .10),
      none of the factors were statistically significant. The Wide-Platform Mk II
      implant used in this population group was associated with a high failure rate,
      but the failure rate was not related to any specific risk factors reviewed.

PMID- 11324210
TI  - A prospective clinical study evaluating the safety and effectiveness of narrow
      diameter threaded implants in the anterior region of the maxilla.
AB  - The aim of the present study of single-tooth implants was to compare the success
      rate and marginal bone resorption of a narrow-diameter self-tapping implant
      placed in less available bone volume with the standard-diameter self-tapping
      implant placed in a well-dimensioned alveolar process. A new abutment technique
      and a different permanent abutment design were also evaluated. Fifty-five
      patients were included in the study; 27 patients received 28 standard-diameter
      (3.75-mm) implants, and 28 patients received 32 narrow-diameter (3.25-mm)
      implants replacing either a central or a lateral incisor in the maxilla. In an
      attempt to create an ideal emergence profile and to regenerate papillae,
      individual acrylic resin tooth-shaped temporary abutments were fabricated, based
      on impressions made immediately following implant placement, and connected to the
      implant after 6 months. A minimum of 2 months were then allowed before definitive
      restorative procedures were performed. Impressions were always made at the
      implant level. Follow-up examinations were performed at 6 months after loading
      and 1, 2, and 3 years after loading. Two narrow-diameter implants were lost after
      6 months, but no other failures were subsequently observed in any of the groups
      after that. In both groups, marginal bone loss followed the same pattern and was
      recorded radiographically to be a mean of 0.4 mm from the first to the last
      examination.

PMID- 11324211
TI  - Patients with reconstruction of craniofacial or intraoral defects: development of
      instruments to measure quality of life.
AB  - Patients with reconstruction of craniofacial or intraoral defects experience a
      profound impact on their quality of life (QOL). This impact on QOL is influenced
      by the patients' medical conditions and the treatment interventions. Instruments
      to measure general QOL have been available for many years. A major criticism of
      QOL instruments is that too often the questions are not specific to the
      particular problems of a disease or condition. A search of the literature
      regarding QOL measurement for patients with maxillofacial implant-supported
      prostheses produced a short list of instruments, none of which were sufficiently
      developed or suited to the patients involved in reconstructive treatment. This
      study was designed to develop pretreatment and posttreatment questionnaires for
      measuring QOL for patients with reconstruction of a craniofacial defect and
      patients with reconstruction of loss of specific intraoral structures utilizing
      an implant-supported prosthesis (e.g., severe resorption of the maxilla or
      mandible or both). The goal was to develop brief, targeted instruments for this
      specific patient population. The produced instruments were sensitive and easy to
      administer and score, and no disruption of clinical care occurred with the
      administration of the questionnaires. The instruments were used with equal
      success both in face-to-face interviews and via mail.

PMID- 11324212
TI  - A comparative clinical investigation of 2 early loaded ITI dental implants
      supporting an overdenture in the mandible.
AB  - The purpose of this prospective clinical study was to evaluate the efficacy of
      early loading of implants and to provide evidence to support simplified treatment
      of mandibular edentulism by using an implant designed for 1-stage surgery,
      combined with ball abutments to circumvent the need for a fixed prosthodontic
      superstructure. Historically, the recommended time between the placement and
      functional loading of dental implants has been 3 months in the mandible. This
      recommendation is the result of a systematically chosen healing time during
      development of implant treatment. In recent years, histologic and experimental
      studies have shown that specially designed implants can result in increased bone
      to-implant contact at earlier healing times. Accordingly, these implants can be
      placed into function faster than previously recommended. In this study, 21
      patients aged between 61 and 85 years with edentulous mandibles were included.
      All received 2 titanium plasma-sprayed, solid-screw dental implants in the
      interforaminal region. Ten patients had the implants loaded with an overdenture
      connected with ball abutments after 3 months (control group). The other 11
      patients (test group) had prostheses connected to the ball abutments after a
      maximum of 3 weeks. Marginal bone resorption, Periotest values, and patient
      satisfaction were evaluated. The cumulative post-loading implant survival rate
      was 100% for both groups after 24 months. Marginal bone resorption after 1 year
      around all implants ranged from 0 to 2 mm (no significant differences between
      groups; P < .05). Periotest values for all implants 1 year after loading were
      below zero (range -1 to -6). The results of this clinical trial suggest that
      successful early loading of 2 implants is possible provided there is
      uncomplicated implant placement.

PMID- 11324213
TI  - CrossLaps and beta-glucuronidase in peri-implant and gingival crevicular fluid.
AB  - Collagen degradation products of the carboxyterminal region possibly reflect bone
      and attachment loss. In the present study, the Serum CrossLaps One-Step enzyme
      linked immunosorbent assay was used to determine a specific part of the
      carboxyterminal region of type I collagen, the CrossLaps. Samples of peri-implant
      and gingival crevicular fluid of 111 implants and 53 teeth from 47 partially or
      completely edentulous patients were examined in reference to levels of CrossLaps
      and beta-glucuronidase (beta G), an established marker of periodontal disease.
      Clinical probing pocket depth (PPD), bleeding on probing (BOP), plaque
      accumulation, mobility, radiographic bone loss, and the occurrence of
      Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, and Prevotella
      intermedia were assessed. The mean values were: for PPD at implants 3.76 +/- 1.41
      mm, at teeth 3.44 +/- 0.88 mm; for beta G at implants 0.364 +/- 0.392 pU/min, at
      teeth 0.314 +/- 0.209 pU/min; for CrossLaps at implants 0.069 +/- 0.059 pmol/min,
      at teeth 0.082 +/- 0.053 pmol/min. Bleeding on probing was significantly higher
      on implants than on teeth (McNemar test, P = .004). No significant difference of
      beta G levels was found between teeth and implants (Wilcoxon test). A negative
      correlation was found between beta G levels and CrossLaps levels at teeth
      (Pearson-rank correlation, P = .002). On implants, no significant correlation of
      these 2 parameters was seen, but significant correlations were found between
      sulcus fluid flow rate and PPD (P = .012), beta G levels and bone loss (P <
      0.0005), and CrossLaps levels and PPD (P = .011). CrossLaps can be detected in
      both gingival and peri-implant crevicular fluid. While rising levels of beta G
      may indicate acute peri-implantitis, CrossLaps may not, but could play a role as
      a marker of ongoing attachment loss.

PMID- 11324214
TI  - Maxillary overdentures retained by splinted and unsplinted implants: a
      retrospective study.
AB  - The purpose of this retrospective study was to evaluate the clinical performance
      of and patients' satisfaction with maxillary overdentures retained by splinted
      and unsplinted implants. Patients who had been treated with maxillary implant
      retained overdentures because of functional problems with conventional complete
      dentures were identified and invited to participate in the study. A total of 16
      patients fulfilled the enrollment criteria and agreed to participate. Eleven
      patients were treated with bar-retained overdentures with 3 to 6 clips (mean
      follow-up 32 months), and 5 patients wore overdentures retained by 2 to 6 ball
      attachments (mean follow-up 54 months). All subjects were satisfied with their
      prostheses, and most subjects experienced improvement in their oral function
      after treatment with implant-retained overdentures. At the time of clinical
      examination, 92% (n = 77) of the 84 implants placed were functioning
      satisfactorily. The cumulative survival rate for the implants after 72 months was
      90%. Loss of bone support correlated with peri-implant probing depth (r = 0.29; P
      < .02). No differences in mean bone loss between the subjects with ball-retained
      or bar-retained overdentures were found. The presence of plaque or peri-implant
      bleeding was not associated with the type of attachment.

PMID- 11324215
TI  - Immediate loading of single-tooth implants: immediate versus non-immediate
      implantation. A clinical report.
AB  - The hypothesis of the present study was that immediate loading of implant
      supported restorations replacing single missing teeth could be a successful
      procedure. The present study compared the clinical success of immediately loaded
      single-tooth implants placed in fresh extraction sites to that of immediately
      loaded single-tooth implants placed in healed sites. From the years 1997 to 1998,
      26 patients, ranging in age from 18 to 70 years, presented for the placement of
      28 immediately loaded implants intended to support single-tooth ceramometal
      restorations. Nineteen implants were placed into fresh extraction sites, and 9
      implants were placed into healed sites. Temporary prefabricated acrylic resin
      crowns were prepared and adjusted. At the time of traditional second-stage
      surgery (3 to 6 months after implantation), the implants were restored with
      single-tooth ceramometal prostheses. The survival rates were 82.4% and 100% for
      immediate and non-immediate implants, respectively. Follow-up ranged from 6 to 24
      months from the day of implant placement, with a mean of 13 months for the
      immediate implants and 16.4 months for the non-immediate implants. Radiographic
      marginal bone loss after 3 to 6 months did not extend beyond the abutment-implant
      junction. Within the limits of the present investigation, immediate loading of
      single-tooth implants placed in healed sites is a possible treatment alternative.
      Immediate loading of single-tooth implants placed in fresh extraction sites
      carried a risk of failure approximating 20% in this patient population.

PMID- 11324216
TI  - Peri-implant bone loss: management of a patient.
AB  - This clinical report presents the prosthodontic management of early peri-implant
      bone loss in a partially edentulous patient. Two narrow Branemark implants (3.3
      mm in diameter) were placed to retain a mandibular implant prosthesis in the area
      of the mandibular left second premolar and first molar. Two weeks after the
      prosthesis was put into function, the distal implant exhibited soft tissue
      reactions. Radiographically, bone corresponding to 4 threads and 7 threads was
      lost at the mesial and distal sites, respectively. After occlusal load reduction
      was made to the existing prosthesis, bone was observed to have regenerated
      sufficiently to restore the defect radiographically, though not to the original
      level. The bone remained at a similar level at 36 months after treatment.

PMID- 11324217
TI  - [Significance of trypsinogen gene mutations in the etiology of hereditary
      pancreatitis].
AB  - Hereditary, chronic pancreatitis is an autosomal dominant genetic disorder,
      frequently associated with two point mutations in the cationic trypsinogen gene.
      The mutations result in characteristic changes in the amino-acid sequence of
      trypsinogen: an arginine residue at position 117 is changed to histidine (Arg117-
      >His) or an asparagine residue at position 21 is replaced by isoleucine (Asn21-
      >Ile). Current opinion on the pathogenesis of hereditary pancreatitis suggests
      that the mutations lead to increased trypsin activity in the pancreatic tissue as
      a result of enhanced autoactivation of trypsinogen or decreased autocatalytic
      degradation (autolysis) of trypsin. To investigate the relationship between the
      altered properties of mutant trypsinogens and the pathomechanism of pancreatitis,
      wild-type and two mutant forms of recombinant human cationic trypsinogen were
      produced and autoactivation of trypsinogens and autolysis of trypsins were
      studied. The results indicate that trypsin stabilization (i.e. decreased
      autolysis) caused by the Arg117-->His mutation may contribute to the development
      of pancreatitis, however, the Asn21-->Ile mutation has no such effect. In
      contrast, enhanced autoactivation of mutant trypsinogens may contribute to the
      pathogenesis of both forms of hereditary pancreatitis. This notion is strongly
      supported by the clear correlation between the autoactivation rates of mutant
      trypsinogens and the severity of clinical symptoms.

PMID- 11324218
TI  - [Ischemic stroke in young adults].
AB  - Ischemic strokes appear infrequently in young adults before age of 45. It is
      important to find the etiologic factors and treatment them adequately for
      preventing the recurrence. Between 1988-1998 eighty-four stroke patients were
      observed in the authors' clinic. Smoking and hyperlipidemia were the most
      frequent risk factors. These were different from other studies and they can
      related to the national eating habits. Atherosclerosis (33.3%), prothrombotic
      states (15.5%) and cardiogenic embolism (9.5%) were found in the background, but
      the etiology remained unclear in 17.7% of patients. Neurological signs improved
      in 77.4% of patients, but deterioration was found in 3.6% and 7% of patients died
      in spite of appropriate therapy. The frequency of the stroke in young adults and
      distribution of etiological factors were similar to the other studies. The
      occurrence of above mentioned risk factors--mainly the frequently observed
      hyperlipidemia--reflects local feeding features. Because of the limited
      diagnostic tools some cases remained unclear.

PMID- 11324219
TI  - [Validity of chromosome analysis and bleomycin sensitivity assay in the
      prevention of head and neck cancer in Hungary].
AB  - Because of unfavourable cancer mortality statistics of Hungary, the search of
      different biomarkers is one of the most important demands of the national primary
      cancer prevention programme. The aim of this study was to clarify the usefulness
      of bleomycin sensitivity assay elaborated in the USA, and to find whether it
      serves under our environmental conditions as a biomarker of individual
      sensitivity and risk for head and neck cancer, beside chromosomal aberration
      analysis. The test reflecting mutagen sensitivity is based on the mean values of
      chromatid breaks induced by bleomycin in vitro in a single lymphocyte (break/cell
      = b/c). Since cancer formation is influenced by environmental mutagens, in
      contrast to others, their 111 head and neck cancer patients were matched not only
      with 230 healthy controls (106 nonsmokers and 124 smokers), but also with 44
      strong alcoholic and smoking patients with liver diseases whose lifestyle did not
      differ from that of the cancer patients. According to the results of conventional
      chromosome analysis, the aberrant cell frequency was the highest in the cancer
      patients (3.34%), while in the alcoholics (2.73%) and healthy smokers (2.88%) the
      values were similar. Thus, the genetic instability occurring in the form of
      elevated rate of spontaneous chromosomal aberrations was mostly expressed in head
      and neck cancer patients. Mutagen sensitivity measured by the b/c values of
      bleomycin assay was significantly higher in both the cancer (1.16 b/c) and the
      alcoholic patients (1.34 b/c) compared with the controls (1.0 b/c). The bleomycin
      sensitivity assay, therefore, seems to be the biomarker not only of cancer, but
      also the disease of the same etiology such as alcohol-related liver disease.
      However the method is not suitable for the assessment of individual cancer risk
      because of the high variability of b/c values in each group, and their
      considerable overlapping with the controls. It can also be supported with
      extremely high mutagen sensitivity of Hungarian controls (63 and 67%), which is
      three-fold of US values (23%). The bleomycin sensitivity assay is not a selective
      biomarker if comparing to the controls, probably due to the action of more
      complex exposures under Hungarian environmental conditions. When estimating
      cancer risk, the results of conventional chromosome analysis offer more
      information than bleomycin sensitivity assay.

PMID- 11324220
TI  - [Renal papillary necrosis in a diabetic patient].
AB  - The authors present a case of a young diabetic patient with acute symptoms of
      pyelonephritis. The specific and permanent antibiotic treatment was ineffective
      and septic condition developed complicated by renal papillary necrosis. Because
      of the strong flank pain extensive examinations were done with negative result.
      The patient's condition was improving only slowly and there was need for
      treatment after her discharge as well. Long-term antibiotic treatment is an
      effective therapy to cure this previously deadly complication. Special attention
      should be given to diabetic patients because of frequent urinary tract infection
      and increased risk of renal damage among them.

PMID- 11324221
TI  - [Writings of Laszlo Nemeth about Lajos Markusovszky].

PMID- 11324222
TI  - [The beginnings of bile stone surgery in Hungary, 1889-1895].

PMID- 11324223
TI  - [Some debatable problems of the therapy of prostatism. Classical article. 1925].

PMID- 11324224
TI  - [Emblem of medicine and dracunculiasis in Egypt].

PMID- 11324225
TI  - Smilematters. Patient fact sheet. Be a good sport about mouthguards.
AB  - It is important to wear a mouthguard that is fitted properly to help prevent
      injuries to your teeth, lips, cheeks, tongue and jaw. Talk to your dentist about
      which one of the three kinds of mouthguards is right for you: ready-made, boil
      and bite, or custom-fitted. Be sure to wear you mouthguard during practice as
      well as during games.

PMID- 11324226
TI  - Sewer rats.

PMID- 11324227
TI  - Internet prescribing/jurisdiction over out-of-state dentists.

PMID- 11324228
TI  - Programs of special interest to our life members.

PMID- 11324229
TI  - Dr. George Bletsas: ninth district candidate for 2001 ADA president-elect.
      Interview by Michael G. Maihofer.

PMID- 11324230
TI  - Answering your Internet questions.

PMID- 11324231
TI  - [Histopathology of the alcoholic hepatitis and mesenchymal cells].
AB  - Alcoholic hepatitis is one of the type of alcoholic liver diseases (ALD). There
      are definite histopathological criteria; presence of Mallory bodies and PMN
      leukocytes. In Japan, it has been believed that alcoholic hepatitis is very rare
      and alcoholic fibrosis is common type in ALD. On the other hands, some american,
      authorities consider that severe ballooning of hepatocytes with slight fibrosis
      is also inflammatory state, alcoholic hepatitis. Histological criteria is
      controversial. Generally, fibrosis believed to be a histological marker of
      chronic inflammation. However, in ALD, there is primary fibrosis, specific
      fibrosis produced by direct stimulation of alcohol or its metabolites on
      mesenchymal cells. On the fibrogenesis in hepatic lobules, the mesenchymal cells
      represented by Ito cells play main role. Ito cells show morphological and
      immunohistochemical heterogeneity depending on its physiological condition. On
      the other hand, Ito cells also show various degrees of transitional changes
      associated with fibrogenesis. Then, morphological and immunohistochemical
      appearance of Ito cells is very complicated. Recently, it is considered that
      these differences means different cell populations of the fibroblast lineage with
      fibrogenic potential.

PMID- 11324232
TI  - [Drinking behaviors of Japanese adolescents' problem drinker--report of 1996
      national survey].
AB  - The first national survey of Japanese adolescent drinking behaviors was conducted
      in 1996. Based on the survey results, this study focused on high risk drinking
      behaviors of Japanese adolescent problem drinkers. The subjects were 42,183
      junior high school students and 72,396 senior high school students who responded
      to questions on drinking frequency and drinking quantity among the national
      survey subjects. The subject students were divided into three groups: normal
      adolescents, drinkers and problem drinkers by the QF scale. The problem drinkers
      according to the QF scale accounted for 3% of the junior high school students and
      14% of senior high school students. Problem drinkers among both junior and senior
      high school students had characteristic drinking behaviors such as various
      drinking occasions, obtaining alcoholic drinks by various methods, drinking hard
      liquor, and many instances of vomiting or blackouts due to drinking. Many problem
      drinkers considered that the national law prohibiting minors from drinking was
      unnecessary because they have the right to decide whether to drink. Both junior
      and senior high school problem drinkers showed high risk drinking behaviors.

PMID- 11324233
TI  - Two models of ethanol withdrawal kindling.
AB  - The phenomenon of ethanol withdrawal kindling was examined using two different
      paradigms of ethanol treatment in rats and mice. In the first protocol, male
      Wistar rats were treated by ethanol inhalation for 14 days before withdrawal.
      Ethanol exposure was repeated three times with two days abstinence between
      treatments. In the second protocol, male C57BL/6 mice were fed liquid diet
      (Lieber DeCarli) containing 6.5%(v/v) ethanol for ten days. Feeding was repeated
      five times separated by 24 hr intervals. After both treatments, either
      spontaneous or handling-induced withdrawal behaviours were significantly
      intensified by sequential withdrawals. These results support the kindling
      hypothesis of ethanol withdrawal and provide models to develop potential
      pharmacological tools to attenuate enhanced withdrawal severity and to study the
      molecular mechanisms underlying this phenomenon.

PMID- 11324234
TI  - Vitamin intake, recommended intake, and gender differences.
AB  - The role of vitamins in promoting good health and preventing disease is currently
      gaining recognition. Daily iron and folate intake should be higher in
      menstruating women than in men of similar age, while lower total intake of
      vitamins A, B, E, K, and zinc are based on body size, and recommendations are
      usually lower in women compared to men. Adequate daily intake can be achieved
      through a balanced diet for most nutrients and vitamins. Exceptions are the need
      for supplementation of most vitamins and folate in pregnant women and for vitamin
      D and calcium in older individuals.

PMID- 11324235
TI  - We are what we say.

PMID- 11324236
TI  - Estrogen protects against hypertension in the spontaneously hypertensive rat, but
      its protective mechanism is unrelated to impaired arterial muscle relaxation.
AB  - OBJECTIVES: To determine if estrogen acutely and directly alters arterial muscle
      relaxation, if estrogen is responsible for gender dichotomy in hypertension, and
      if arterial muscle from female spontaneously hypertensive rats (SHR) is slow to
      relax as is muscle from male SHR compared with arterial muscle of normotensive
      Wistar-Kyoto rats (WKY). METHODS: Relaxation rates of isometrically contracted
      arterial muscle from male rats were measured before and after addition of beta
      estradiol. Blood pressure (BP) was monitored in intact male and female SHR and
      WKY and in ovariectomized and estrone-treated ovariectomized SHR and WKY.
      Relaxation rates of maximum isometric contractions of arterial muscle excised
      from male SHR and WKY and female SHR and WKY with varying chronic estrogen status
      were measured. RESULTS: Beta-estradiol had no direct, acute effect on arterial
      muscle force or relaxation. Intact and estrone-implanted SHR females had
      significantly lower BP than males. Ovariectomized SHR developed high BP
      equivalent to that of males. Arterial relaxation was slower in both male and
      female SHR compared with WKY. CONCLUSIONS: Estrogen lowers BP in female SHR.
      Strain differences in relaxation rates are independent of gender and estrogen
      status. Estrogen has no effect on arterial muscle relaxation, suggesting another
      mechanism for the protective effect of estrogen in hypertension.

PMID- 11324237
TI  - Gender differences in the effect of genistein on vascular smooth muscle cells: a
      possible cardioprotective effect?
AB  - OBJECTIVE: Isoflavones are a class of phytoestrogens found abundantly in
      soybeans. They share structural similarity to 17-beta-estradiol, bind to the
      estrogen receptors alpha and beta, and produce estrogenic or antiestrogenic
      effects. Atherosclerosis is an inflammatory-mediated fibroproliferative response
      to injury to the arterial wall. Vascular smooth muscle cells (VSMCs) are the
      prominent cells in the atherosclerotic plaque. VSMCs contain estrogen receptors
      and, at physiologic concentrations, 17-beta-estradiol-inhibited proliferation of
      VSMCs from sexually mature female pigs. We determined if genistein inhibited
      proliferation and altered matrix protein production in VSMCs from coronary
      arteries of sexually mature pigs. METHODS: The effect of genistein on cell
      proliferation was assessed by thymidine incorporation. The effect of genistein on
      matrix protein production in VSMCs was assessed by Western blot analysis. RESULTS
      AND CONCLUSION: We demonstrate gender-specific effects in the proliferation of
      coronary artery vascular smooth muscle cells obtained from a sexually mature pig
      model treated with genistein at physiologically relevant concentrations. There
      were no differences in the amount of estrogen receptor proteins between the
      genders, suggesting that nongenomic mechanisms may be responsible for these
      effects. Genistein also upregulated matrix protein expression, which may be
      related to the formation of the atherosclerotic plaque. Overall, these results
      suggest possible cardioprotection by genistein.

PMID- 11324238
TI  - Etiology of differences in hematocrit between males and females: sequence-based
      polymorphisms in erythropoietin and its receptor.
AB  - INTRODUCTION: Males have a higher hematocrit (Hct) than females. The cause of
      this gender-based difference is unclear. We sought to determine whether
      polymorphisms of the erythropoietin (EPO) gene or of its receptor (EPOR) explain
      this situation. METHODS: We designed primers for the EPO and EPOR genes.
      Previously undescribed polymorphisms were found based on band migration on
      polyacrylamide gel, and when then sequenced. The distribution of these
      polymorphisms was studied in a population of 819 non-iron-deficient, healthy
      blood donors. To test the gender differences, analysis was done based on groups
      defined by Hct levels. The chi-square statistic was used to compare the frequency
      differences between groups, with P < .05 considered statistically significant.
      RESULTS: We found previously reported polymorphisms in both the EPO and EPOR
      genes. Sequence analysis showed that the EPO polymorphism was due to a difference
      in the repeat copy number of the tetranucleotide cytosine adenine cytosine
      thymine (CACT) at position 2153. A previously undescribed 12th allele was found
      for the EPOR polymorphic site. Statistical analysis showed that the EPOR alleles,
      EPORA1 and EPORA10, were present at a significantly higher frequency in females
      than in males (P = .027 and P = .041, respectively), and EPOR5 was found less
      frequently in females than in males (P = .048). The allelic frequency of the EPO
      polymorphism was not significantly different by gender or Hct groups. DISCUSSION:
      These results suggest that the variation of Hct level by gender may have a
      genetic basis. The sequence-based polymorphism for EPOR may be partly responsible
      for this gender-based variation in Hct level. These findings offer new clues to
      understanding Hct variation in the general population and to elucidating
      mechanisms of controlling Hct levels.

PMID- 11324239
TI  - Gender-related physiologic differences in human neonates and the greater
      vulnerability of males to developmental brain disorders.
AB  - OBJECTIVE: To examine whether gender-specific physiologic differences are present
      at birth and can be a basis for gender-specific vulnerability to developmental
      disorders in males. We report on three studies of male-female physiologic and
      structural differences in neonates and their relevance to observed differences in
      the incidence of developmental disorders in males. METHODS: Study I: 56 neonates
      were examined for cardiac reactivity to the Moro reflex. Study II: 863 neonates'
      basic anthropometric data were examined to demonstrate gender-specific
      differences in body proportions as a possible basis for psychophysiologic
      differences. Study III: Developmental data on 1000 one- to 26-week-old infants
      were analyzed for gender-specific developmental differences in rhythmic patterns
      of sleeping and eating. RESULTS: Study I: There were gender-related differences
      in heart rate reactivity (male > female). Study II: Male newborns had
      significantly larger head/chest proportions, suggesting that they may have a
      greater metabolic demand, related to brain size. Study III: Mothers reported that
      infant males' sleeping rhythm developed significantly later than females', and
      that they slept for shorter periods at night. CONCLUSIONS: Gender-related
      vulnerability in brain development is proposed, based on physiologic differences
      during a specific early sensitive period in development. This hypothesis may help
      to explain the overrepresentation of males reported for most developmental
      disorders.

PMID- 11324240
TI  - Gender-specific medicine in pediatrics.
AB  - As pediatricians have always known, boys and girls are different. Many pediatric
      diseases and syndromes are either more common or more severe in one sex than in
      the other. Puberty brings about emotional and physical changes that are obviously
      very different in males and females. In addition, certain "adult" conditions with
      gender differences, such as osteoporosis and long QT syndrome, may be present or
      preventable in the early years. Physicians should strive to understand these
      differences so that they can tailor medicine and other therapies to specifically
      meet the needs of each gender.

PMID- 11324241
TI  - Caring for women with inflammatory bowel disease.
AB  - Crohn's disease and ulcerative colitis are chronic inflammatory conditions
      involving the gastrointestinal tract. Although many aspects of the management of
      these diseases are identical for all patients, some issues that are specific to
      women are not necessarily part of routine care. Gender-specific issues such as
      menses, fertility, pregnancy, and menopause are often overlooked and mismanaged.
      Women and men also have different psychological concerns arising from the
      disease. Health care providers, regardless of their primary focus, should be
      aware of these differences and should be familiar with certain general
      information on gender-specific issues, reviewed in this article.

PMID- 11324242
TI  - Prevalence of hormone replacement therapy and antidepressant use in peri- and
      postmenopausal women.
AB  - OBJECTIVE: To examine the prevalence of hormone replacement therapy (HRT) and
      antidepressant use in peri- and postmenopausal women. DESIGN: Prevalence survey.
      SUBJECTS: Peri- and postmenopausal outpatients (N = 253) at five medical clinics.
      METHODS: Participants completed a 47-item questionnaire requesting information on
      mood changes associated with menstruation, childbirth, oral contraceptive use,
      and menopause. Peri- and postmenopausal participants were asked to rate the
      severity of dysphoric symptoms experienced during the menopausal transition and
      to specify whether HRT, antianxiety medication, or antidepressant medication
      relieved the symptoms. RESULTS: Forty percent of respondents experienced more
      severe depression than anticipated during menopause, but only 8% were treated
      with antidepressants. Forty-six percent of respondents were treated with HRT.
      CONCLUSIONS: The data suggest that antidepressant and antianxiety medications are
      more helpful than HRT in relieving peri- and postmenopausal depression or
      anxiety. However, most women managed the mood changes associated with menopause
      without psychopharmacologic intervention. This is consistent with other reports
      on the transitory nature of peri- and postmenopausal depression for most women.

PMID- 11324243
TI  - Gender-specific issues in the treatment of migraine.
AB  - Migraine is approximately three times more common in women than in men. Women
      tend to have longer attacks and are more likely than men to experience aura with
      migraine, but both sexes can experience frequent and severe attacks. Treatment
      principles for migraine and guidelines for the use of prophylactic and abortive
      therapies are generally consistent between males and females. However, due to
      hormonal changes induced in the female during menstruation, oral contraceptive
      use, pregnancy, and menopause, gender-specific therapeutic strategies are often
      necessary when treating migraine in females.

PMID- 11324245
TI  - [Perfusion, a method for optimal home perfusion].

PMID- 11324246
TI  - [A professional guideline for nurses].

PMID- 11324247
TI  - [Nurses during the First World War; health disasters during the initial phases of
      conflict].

PMID- 11324248
TI  - [News from Europe Bulgaria, a country undergoing total change].

PMID- 11324249
TI  - [The nurse and the socially deprived].

PMID- 11324250
TI  - [Nursing service for the socially deprived].

PMID- 11324251
TI  - [To be a resource for the socially deprived].

PMID- 11324252
TI  - [Health and poverty: what kind of in-hospital nursing care is needed?].

PMID- 11324253
TI  - [The hospital as refuge].

PMID- 11324254
TI  - [Excluded from the health care system, on the example of the Sevigne Center at
      Lyon].

PMID- 11324255
TI  - [The nurse facing the health problems of the homeless].

PMID- 11324256
TI  - [Protecting the right to long-term care for the psychotic patient].

PMID- 11324257
TI  - AMS supports ban on smoking in restaurants.

PMID- 11324258
TI  - Report of the Executive Vice President.

PMID- 11324259
TI  - Regulations passed by the board and/or amended during 2000.

PMID- 11324260
TI  - Arkansas Health Care Access Foundation Inc.

PMID- 11324261
TI  - Arkansas Department of Health 2000 report.

PMID- 11324262
TI  - "Pouring rights"--another view.

PMID- 11324263
TI  - Article misleading?

PMID- 11324264
TI  - Fraud and abuse/compliance programs for dentists.

PMID- 11324265
TI  - The truth behind the prescription drug crisis.

PMID- 11324266
TI  - Micrometric measurements by scanning electron microscope (SEM) for dental age
      estimation in adults.
AB  - Determining age from dental structure is a well documented forensic procedure and
      the data may be used as auxiliary information in identification. In this study 20
      measurements of different variables in incisor teeth were obtained using a SEM
      micrometric scaler and the results were stastically correlated with age by the
      multiple regression method. A formula was then derived from the calculations for
      age estimation which gave statistically acceptable results. Gender differences
      were also investigated and when separated delivered even stronger correlation.

PMID- 11324267
TI  - Comparison of bitemarks left in foodstuffs with models of the suspects'
      dentitions as a means of identifying a perpetrator.
AB  - In a recent court case, a comparison was made between an impression of marks left
      in cheese at a murder scene and a set of study models of one of the suspects. The
      court was reluctant to accept the validity of the pattern-associated comparison
      that was used in the identification. This study compared marks made in cheese,
      butter and cooked potato with study models taken from volunteers. Pattern
      associated comparison was the method used. Eighty pair-wise comparisons were made
      by two odontologists. The examiners correctly identified all the true matches
      from among the eighty comparisons as well as selecting the dental models for
      which there were no corresponding silicone impressions. In the absence of
      identifiable fingerprints or DNA samples, the method can be employed for matching
      left in foodstuffs to the dentitions of suspects.

PMID- 11324268
TI  - Postmortem tooth loss in human identification processes.
AB  - Teeth provide essential data for human identification. However, they are
      frequently lost during the process of skeletonization or under manipulation
      during exhumation. Because of the high frequency of postmortem tooth loss, this
      phenomenon was examined in three different samples, in an attempt to simulate the
      actual circumstances experienced in the forensic processes of identification of
      human remains. The method employed aimed to describe and quantify dental spaces,
      distinguishing between loss after death or before by extraction. The results
      showed a high prevalence of postmortem tooth loss: 41.37% in sample A, 56.83% in
      sample B and 3.96% in sample C. These losses were most frequent in the maxillary
      incisor group in all three samples analysed. These data underline the need for
      redoubled care in recovery, transportation and storage of crania, so that teeth
      are not lost, which could seriously compromise the identification process.

PMID- 11324269
TI  - Tooth root colour as a measure of chronological age.
AB  - The purpose of this study was to assess a possible colour shift in the root
      surfaces of adult human teeth and if so, whether this colour change is related to
      chronological age. Teeth extracted from persons of known age and gender were
      obtained from Ontario dental practitioners and grouped into five-year age ranges.
      Three experiments were undertaken: (1) to identify a possible difference in
      yellow colouration between the four surfaces of tooth roots (mesial, distal,
      lingual, and buccal), (2) to investigate the difference in yellow colouration of
      tooth roots between non-molar teeth and molar teeth and (3) to assess the
      correlation between the age of teeth and root colour saturation for yellow,
      magenta, cyan and black. The teeth in all investigations were scanned by a flat
      bed digital colour scanner with a Kodak colour scale control and viewed on a
      colour computer monitor. In the first two experiments the yellow colour
      saturation of the root surfaces was measured at six points on each root using
      Photoshop 5.0 software. A significant difference was observed in the percentage
      yellow colour saturation between the mesial and the other three anatomical
      surfaces (p < 0.01), and between the root surfaces of non-molar and molar teeth
      (p < 0.01) (ANOVA with Bonferroni post-test). The authors then randomly assigned
      tooth surfaces to select an equivalent number of posterior and anterior teeth in
      the study, assessing the relationship between age and root colouration. Four
      points of colour measurement on 40 teeth (sample size permitting, see Table 1)
      for each known age and gender were assessed for colour saturation (cyan, magenta,
      yellow and black). The correlation of chronological age to colour saturation was
      linear for all colours, with correlation coefficients ranging from r = 0.81 to r
      = 0.94. The high correlation values strongly support the conclusion that
      chronological age is related to increased root colouration.

PMID- 11324270
TI  - Wounding dynamics in distorted bitemarks: two case reports.
AB  - An essential factor involved in distortion of bitemarks on the skin is the
      dynamics of biting related to the location on the body. This study describes the
      comparison between the identification of bitemarks left on different regions of
      the victims' bodies in two homicide cases. The findings indicated that a stepwise
      dynamic comparison of serial adjacent marks with a part of the dentition in
      consideration of movement of the jaws and distortion of the skin was useful in
      identifying matching points. The identification process indicated possible
      wounding dynamics of biting.

PMID- 11324271
TI  - Tissue engineering in periodontics using rhBMP-2.
AB  - The results of these studies show that rhBMP-2 clearly enhances regeneration in
      periodontal defects (Figures 2&3). The extent of regeneration appears to be
      significantly influenced by the nature of the carrier material used to deliver
      the rhBMP-2 to the periodontal wound. While the positive effects of rhBMP-2 on
      osteogenesis are well established, less is known about the way in which rhBMP-2
      effects cementogenesis, or its role in the formation of a new periodontal
      ligament. From the studies reviewed, it would appear that rhBMP-2 facilitate in
      the formation of cellular cementum on previously denuded root surfaces. This
      newly formed cementum has also been shown to support an organised periodontal
      ligament attachment. Mechanisms related to the possible role of rhBMP-2 in
      ankylosis are presently unclear and will require further investigation as such
      sequelle may complicate the clinical utility of rhBMP-2 in periodontal
      regeneration. Root resorption has also been reported in the above mentioned
      studies and appears to be related to the concentration of rhBMP-2. Further
      research directed at understanding how different carriers influence the way in
      which the rhBMP-2 is released during wound healing should assist researchers with
      how to best apply these bioengineered proteins to ultimately achieve a more
      predictable regeneration of the periodontal attachment apparatus. Moreover,
      additional research into the differing biologic effects of other members of the
      BMP family of proteins may also hold further promise in the application of this
      technology to periodontal regeneration.

PMID- 11324272
TI  - An endodontic periapical abscess mimicking a deep periodontal pocket: a case
      report.

PMID- 11324273
TI  - Thoughts from the other side of the globe.

PMID- 11324274
TI  - Management of the peri-implant soft tissues.
AB  - To provide a patient with an implant supported restoration that is functional and
      aesthetic requires effective diagnosis. Deficiencies in the bone and soft tissue
      can be dealt with in planning, and decisions can be made regarding what surgical
      corrections are indicated, and when these will be most effectively performed.

PMID- 11324275
TI  - [Menstrual cycle: not anymore a periodic basis: this is what many women wish].

PMID- 11324276
TI  - [Early diagnosis of cervical cancer has to be revised].

PMID- 11324277
TI  - [Bronchial asthma--an innovative therapy with Atmadisc].

PMID- 11324279
TI  - [Compendium on the subject of hygiene 200l--useful suggestions on the subject of
      health care].

PMID- 11324278
TI  - [Sepsis and multiple organ failure--an interdisciplinary problem in intensive
      medicine].

PMID- 11324280
TI  - [Do new healthcare legislations guarantee dignified and humane care?].

PMID- 11324281
TI  - [Staphylococcal toxin aggravates dermatitis in neurodermatitis].

PMID- 11324282
TI  - [Colorectal surgery--problems and perspectives].

PMID- 11324283
TI  - Three dimensional patient evaluation system.

PMID- 11324284
TI  - Orthodontic rescue of an impacted mandibular second premolar.

PMID- 11324285
TI  - Surgeon general's report.

PMID- 11324286
TI  - Airway compromise and dentofacial abnormalities.

PMID- 11324287
TI  - The courage to care.

PMID- 11324288
TI  - Planning helps new dentists handle high debt.

PMID- 11324289
TI  - Business competencies for contemporary dental practices.

PMID- 11324290
TI  - Strategic planning: a guide to success.
AB  - One of the key business concepts applicable to the contemporary dental practice
      is strategic planning. Just as a dentist diagnoses and treatment plans patients,
      so too should a business diagnose and treatment plan its future. Strategic
      planning offers a systematic approach for analyzing a current situation and
      creating a work plan toward the future goal.

PMID- 11324291
TI  - Digital dentistry: information technology for today's (and tomorrow's) dental
      practice.
AB  - Digital dentistry is not the wave of the future; it is occurring now. Whether a
      dentist embraces new technology will define his or her practice and, possibly,
      future. The aim of this article is to inform practitioners of the various
      components that constitute a digital dental practice, the technologies available
      today, and those on the horizon.

PMID- 11324292
TI  - Operations management: a tool to increase profitability.
AB  - Operations management enables the efficient utilization of the production systems
      in a business. This paper will address several key elements in the business
      competency of operations management. Specifically, this discussion will review
      the components of a material requirement planning system and a "just-in-time"
      system for inventory control and time management to enable the dentist to monitor
      a portion of the practice's overhead costs.

PMID- 11324293
TI  - Appointment scheduling system: a vehicle for increased productivity.
AB  - Operations management is the design and control of systems responsible for the
      productive use of human resources, equipment, and facilities in the development
      of a product or service. Applying those concepts to appointment scheduling can
      coordinate efficient use of resources. The focus of this paper is to assist the
      dentist and dental team in creating an appointment scheduling system that
      maximizes productivity and profitability.

PMID- 11324294
TI  - Ethics competencies in the business of dentistry.
AB  - Ethics is the systematic study of human conduct examined in the light of moral
      values and principles. It is the most important competency in dentistry, in
      business, and in life. Competency in ethics requires an understanding of its
      accepted principles, and such competency is the obligation of every dental
      professional.

PMID- 11324295
TI  - How can you help your computer support team?

PMID- 11324296
TI  - Prepable ceramic abutments: principles and techniques for the dental laboratory
      technician.

PMID- 11324297
TI  - Hiring more employees? Growth is great, but carries new burden.

PMID- 11324298
TI  - What can you learn from Mardi Gras to make your lab more successful?

PMID- 11324299
TI  - Leaves and fishes: who's in charge?

PMID- 11324300
TI  - Fabrication procedure for an overdenture utilizing the retentive anchor system of
      the ITI Dental Implant System.

PMID- 11324301
TI  - Conduct problems and level of social competence in Head Start children:
      prevalence, pervasiveness, and associated risk factors.
AB  - The purpose of the current project was to determine the prevalence of conduct
      problems, low social competence, and associated risk factors in a sample of 4
      year-old low-income children (N = 426) from 64 Head Start classrooms in the
      Seattle area. Conduct problems and social competence were assessed based on a
      combination of teacher reports, parent reports, and independent observations of
      children interacting with peers in the classroom and with parents at home. We
      examined the relative contribution of a variety of risk factors, including
      maternal history and socioeconomic background, current levels of stress and
      social support, mothers' emotional state, and parenting competence in relation to
      "pervasive" (i.e., at home and school) and "nonpervasive" conduct problems and
      low social competence. Findings indicated similar risk factors for conduct
      problems and for low social competence, with an ordered increase in the number of
      risk factors from normal to "nonpervasive" to "pervasive" groups. Harshness of
      parenting style (i.e., slapping, hitting, yelling) significantly distinguished
      between the three groups for low social competence and conduct problems. Positive
      affect, praise, and physical warmth from mothers were positively related to
      social competence but unrelated to conduct problems.

PMID- 11324302
TI  - Comorbidity of anxiety and depression in children and adolescents: an integrative
      review.
AB  - Much evidence exists documenting the comorbidity of anxiety and affective
      disorders in youth. Furthermore, comorbidity appears to have serious implications
      both in terms of severity of impairment and course of disorder. Despite this,
      little is known about the meaning behind the high rate of co-occurrence of
      anxiety and depression in children and adolescents. Several conditions exist that
      may give rise to comorbidity. Specifically, two disorders may be comorbid when
      there is a high rate of symptom overlap between the disorders, when one
      underlying construct is split into two separate disorders, when the disorders
      share common risk or etiological factors, or because one disorder causes or
      increases the risk of developing the second disorder. The present paper examines
      each of these explanations as they relate to the comorbidity of anxiety and
      depression in youth.

PMID- 11324304
TI  - Home, school, and community partnerships: integrating issues of race, culture,
      and social class.
AB  - The current review is an examination of home-school-community partnerships
      utilizing an ecological approach to understand the influences of race, culture,
      and social class. The ecological approach recognizes that families and schools
      are embedded in communities, and that these settings influence each other and the
      development of children. The roles of race, culture, and social class in the
      development of partnerships between the home, school, and community settings are
      explored. Race, culture, and social class may interact with parent and family
      attributes, teacher and school qualities, and community context. These factors
      are often misunderstood either through under investigation or lack of
      integration. The implications for future research, practice, and policy are
      discussed.

PMID- 11324303
TI  - The evaluation of parental fitness in termination of parental rights cases: a
      functional-contextual perspective.
AB  - This article highlights issues involved in carrying out evaluations for
      termination of parental rights cases and suggests caution for mental health
      professionals doing such evaluations. It argues that current models of parenting
      that come from the child development and child maltreatment fields are too narrow
      in their focus to act as a foundation for such evaluations and are often based on
      research with select groups in our society making them open to bias. Similarly,
      it is argued that traditional assessment measures are limited in their utility
      for responding to the kinds of relational and basic care questions asked in such
      evaluations. A functional-contextual model is offered as an alternative with
      examples of potentially useful measurement strategies. With such a frame as a
      starting point, the field might progress to providing more useful information to
      courts. Future research directions to improve this practice arena are discussed.

PMID- 11324305
TI  - Story comprehension in children with ADHD.
AB  - A wealth of research is available examining children's story comprehension.
      However, little attention has been directed toward understanding the story
      comprehension of children with attention deficit hyperactivity disorder (ADHD).
      The present paper attempts to integrate the developmental literature on
      children's story comprehension with the little that is known about the story
      comprehension processes of children with ADHD. This review is guided by a network
      model of story representation that emphasizes the structure of causal and
      enabling relations between story events. Examination of the available studies
      indicates that children with ADHD lag behind their peers in their understanding
      of causal relations, and that their attentional problems may contribute to
      difficulties in understanding factual information in the preschool years and
      causally related information in the elementary years. Some evidence also is
      presented suggesting that children with ADHD are less effective in taking
      advantage of story structure features in guiding their recall of story events.
      Suggestions for future research are offered that would elaborate our knowledge of
      the developmental progression in the processing of complex information by
      children with ADHD.

PMID- 11324306
TI  - Children's adjustment to parental physical illness.
AB  - We review recent empirical literature examining the impact of parent physical
      illness on child functioning. We review studies of illness characteristics (n =
      16), individual characteristics (n = 6), and family characteristics (n = 6).
      Although children's self-reports indicate heightened distress, parental reports
      do not suggest more problematic functioning. Child adjustment appears to be more
      closely related to perceptions of stressfulness rather than to objective illness
      severity indices. Adolescent girls seem to represent a group at heightened risk.
      Preliminary results suggest that family variables such as cohesion, conflict, and
      individual and family coping styles are important predictors of child adjustment.

PMID- 11324307
TI  - [Hereditary nonpolyposis colorectal carcinoma (HNPCC): surgical aspects].
AB  - 1-5% of all patients presenting with colorectal cancer, have an underlying
      genetic predisposition with an autosomal dominant of pattern of inheritance.
      Recently the underlying molecular genetic pathway of this syndrome known as HNPCC
      (hereditary nonpolyposis colorectal cancer) has been characterized: the
      predisposition is due to a pathogenic mutation in one of the DNA mismatch-repair
      genes. Colorectal cancers are the leading characterisitic of the syndrom and are
      frequently encountered at a young age of onset. However, endometrial cancer,
      stomach cancer, small bowel cancer, urinary tract cancer and skin cancer among
      others are also inherent to the syndrome. Based on the identification of the
      underlying molecular genetic pathway, predictive testing has become an option.
      Once the family-specific underlying pathogenic mutation in one of the DNA
      mismatch-repair genes has been identified in a proband, at-risk family members
      may be offered DNA testing with an unequivocal answer to if or if not they have
      inherited the increased cancer susceptibility. Multiple facets of family DNA
      testing require a multidisciplinary approach integrating clinicians, geneticists,
      psychologists, molecular biologist and pathologists. Mutations are identified in
      a rate of 50-60% of families complying with the Amsterdam criteria for HNPCC. The
      incidence of recta cancer in HNPCC has as yet not clearly been defined, due to a
      lack of unequivocal data. In a retrospective analysis (submitted) rectal cancers
      were encountered in 30% of the HNPCC patients. Half of the patients affected
      developed metachronous colon cancers. It is essential to address the issue of
      prophylactic surgery in HNPCC patients presenting with colorectal cancer:
      Prospective data is required in order to decide which of the options is more
      beneficial for the HNPCC patient presenting with his first colorectal primary:
      subtotal colectomy and ileorectal anastomosis versus restorative proctocolectomy.
      It is evident that apart from the more clinical data quality of life data must be
      evaluated in this study.

PMID- 11324308
TI  - [Hereditary colorectal carcinoma: predictive diagnosis and genetic counseling].
AB  - 5 to 10 percent of colorectal cancers occur due to a genetic predisposition.
      Familial adenomatous polyposis (FAP) and hereditary non-polyposis colorectal
      cancer (HNPCC) belong to the autosomal-dominant inherited colorectal cancer
      syndromes. First degree relatives of affected persons are at high risk for
      colorectal cancer and therefore should undergo regular surveillance programs. The
      genetic background of FAP and HNPCC is known today, but not in every affected
      family the germline mutation causing the inherited disorder can be found. In some
      cases identification of a germline mutation is helpful to confirm a suspected
      diagnosis in a patient. In almost all cases it is of major importance for their
      family members, as it makes genetic testing and prediction of cancer risk
      available for persons at risk. Predictive genetic testing opens up a new
      dimension in relationship between patients and physicians. Test results are of
      great importance for future plans of a person at risk, therefore predictive
      genetic testing should never be performed without genetic counselling.
      Accordingly the German Bundesarztekammer has worked out guidelines for predictive
      genetic testing in hereditary tumours.

PMID- 11324309
TI  - [Chemotherapy of colonic carcinoma in the year 2001].
AB  - The systemic anticancer drug therapy is indicated in the adjuvant as well as in
      the palliative setting. There is an indication for an adjuvant therapy in case of
      Dukes B (stadium II) as well as in Dukes C (stadium III) colon cancer. An
      indication in the palliative setting remains for the Dukes D (stadium IV) colon
      cancer patients. Locoregional chemotherapeutical approaches represent no standard
      procedure and cannot be recommended outside clinical trials because the real
      value of this therapy is unknown due to a lack of large randomized trials. The
      mainstay of treatment of colon cancer is 5-Fluoruracil (5-FU), which should be
      combined with folinic acid in case of bolus (2-4 min. injection) therapy. In the
      adjuvant situation the Mayo scheme administered over a period of half a year
      remains the standard of choice because this procedure is validated by large
      randomized trials and replaces the combination 5-FU + levamisol given over a
      period of one year in former times. In the palliative situation 5-FU based
      therapy remains the goldstandard although more options than 5-FU plus folinic
      acid are now available. Oxaliplatin and irinotecan are approved for the treatment
      of metastatic colon cancer in first line in combination with 5-FU. Capecitabine
      and Ralitrexed are drugs, which are approved outside of Germany and can be used
      as well if indicated. The median survival of patients with metastatic colon
      cancer is between 12 and 18 month. It will be discussed in which way this range
      depends on the chemotherapeutical strategy.

PMID- 11324310
TI  - [Epigastric pain in Fitz-Hugh-Curtis syndrome].

PMID- 11324311
TI  - [Formation of the boundary between the midbrain and the hindbrain: involvement of
      Otx2 and Gbx2 genes].
AB  - We have studied the neuromeric organisation of the mesencephalic-metencephalic
      (mes-met) territory of the avian neural tube using chick/quail transplantation
      experiments and analysing the expression of various regulatory genes in chimeric
      and normal embryos. Homotopic grafts demonstrate the presence of an
      interneuromeric boundary separating the mesencephalic and cerebellar territories
      (the mes-met or midbrain/hindbrain boundary). This boundary is characterised from
      HH10 onwards by the confrontation of the Otx2-Wnt1 and Gbx2-Fgf8 expressing
      domains, while En2 and Pax2 genes are expressed at both sides of the mes-met
      boundary. The evolution of the position of the Otx2/Gbx2 boundary with respect to
      the vesicles and constriction observed within the mes-met domain between stages
      HH10 and HH20, allows us to redefine the fate map of this region and to propose a
      new nomenclature for HH10. Transplantation between the prosencephalic
      neuroepithelium and the mes-met domain shows the possibility of inducing a mes
      met phenotype within the two caudal-most prosomeres, preceded by its
      characteristic genetic cascade. The induction selectively takes place along the
      boundary between the graft (Otx2 positive) and the host cerebellar territory
      (expressing high levels of Gbx2); this includes the induction inside the graft of
      a new Otx2/Gbx2 boundary. Conversely, no induction is ever observed when the
      graft is confronted to the host Otx2 expressing domain. Although Fgf8 may be
      involved in the inductive events, our data strongly suggest that confrontation
      between Otx2 and Gbx2 is essential as an organiser of the mes-met domain.

PMID- 11324312
TI  - [Messenger proteins].
AB  - Many proteins are internalized by live cells following a pathway that differs
      from classical endocytosis. Thus, they gain direct access to the cell cytoplasm
      and nucleus. The same proteins, very often, are secreted even though they lack a
      signal peptide. This very original mechanism of signal transduction opens the way
      to the reinterpretations of several developmental phenomenons and physiological
      observations. In addition, the discovery of this type of intercellular signalling
      has opened the way to the development of widely used peptidic vectors.

PMID- 11324313
TI  - [Molecular genetics of Hirschsprung disease: a model of multigenic
      neurocristopathy].
AB  - Hirschsprung's disease (HSCR, aganglionic megacolon) is a frequent congenital
      malformation regarded as a multigenic neurocristopathy. Three susceptibility
      genes have been recently identified in HSCR, namely the RET proto-oncogene, the
      endothelin B receptor (EDNRB) gene, and the endothelin 3 (EDN3) gene. RET gene
      mutations were found in significant proportions of familial (50%) and sporadic
      (15-20%) HSCR, while homozygosity for EDNRB or EDN3 mutations accounted for the
      rare HSCR-Waardenburg syndrome (WS) association. More recently, heterozygous
      EDNRB an EDN3 missense mutations have been reported in isolated HSCR patients.
      Some of these results were obtained after the identification of mouse genes whose
      natural or site-directed mutations resulted in megacolon and coat color spotting.
      There is also conclusive evidence for the involvement of other independent loci
      in HSCR. In particular, the recent identification of neurotrophic factors acting
      as RET ligands (GDNF and Neurturin) provide additional candidate genes for HSCR.
      The dissection of the genetic etiology of HSCR disease may then provide a unique
      opportunity to distinguish between a polygenic and a genetically heterogeneous
      disease, thereby helping to understand other complex disorders and congenital
      malformations hitherto considered as multifactorial in origin. Finally, the study
      of the molecular bases of HSCR is also a step towards the understanding of
      developmental genetics of the enteric nervous system giving support to the role
      of the tyrosine kinase and endothelin-signaling pathways in the development of
      neural crest-derived enteric neurons in human.

PMID- 11324314
TI  - [Molecular aspects of the expression and regulation of endothelial nitric oxide
      synthase].
AB  - The endothelial isoform of nitric oxide synthase (eNOS) ensures enzymatic
      production of nitric oxide (NO) not only in endothelial cells but also in other
      cell types, such as neurons, platelets, and some epithelial cells. Its
      physiological role has been well defined in some of these cells, such as
      relaxation of vascular smooth muscle cells, or long-term potentiation in neurons,
      owing to knockout experiments. Although constitutively expressed in endothelial
      cells, eNOS mRNA has been shown to be modulated by several physical, biochemical,
      and hormonal factors, acting at the transcriptional or post-transcriptional
      levels. Several functional regulatory elements have been mapped in the eNOS
      promoter, active both in endothelial and non-endothelial cells, and we present
      elements demonstrating that these elements are not sufficient to explain the high
      level of eNOS expression specific to endothelial cells.

PMID- 11324315
TI  - [Nitric oxide and myocardial ischemic preconditioning].
AB  - Preconditioning is an endogenous mechanism of cardioprotection that develops
      secondary to a brief ischemia and a dramatic reduction in infarct size is
      observed when the myocardium undergoes a subsequent and long period of ischemia
      after the induction of preconditioning. Since its initial discovery, it appears
      that the kinetic of preconditioning is biphasic. Early preconditioning is
      effective within 1 to 3 hours after the initial brief ischemia. A second windows
      of preconditioning has been also described within the following 24-48 h. Although
      late preconditioning against myocardial stunning is well established, its
      protection against infarction still remains debated. Whereas nitric oxide is not
      involved in the early preconditioning, its role during the late phase of
      preconditioning has been recently well described. Indeed, nitric oxide triggers
      the delayed cardioprotection through the formation of oxiradicals. This leads to
      the translocation of protein kinase C. Secondary, the activation of the tyrosine
      kinases pathway and the transcriptional factor NF kappa B induces iNOS.
      Therefore, nitric oxide also plays a key role in the late preconditioning
      phenomenon as a mediator of this cardioprotection, although its final effector
      still remains unknown. The knowledge of the mechanisms responsible for
      preconditioning is necessary in order to develop new pharmacological concepts in
      order to protect the heart against ischemia. It is interesting to underline that
      nitric oxide donors are able to mimic late preconditioning.

PMID- 11324316
TI  - [Role of nitric oxide in heart failure].
AB  - The benefit effects of nitric oxide (NO) donors in acute heart failure have led
      to the development of vasodilators as treatment of chronic heart failure.
      However, the mechanisms involved in the effects of NO are complex and still
      discussed. In chronic heart failure, the eNOS downregulation in vascular
      endothelium explains the alteration of endothelial function. In addition, in the
      myocardium, cytokines induce the expression of inducible nitric oxide synthase
      (iNOS) which increase NO production by myocytes and surrounding cells. This
      excess of NO production, associated with anion superoxide synthesis, limits the
      inotropic properties of catecholamines and exert proapoptotic effects. The role
      of NO donors in heart failure treatment is still controversial but by reducing
      preload they improve patient's symptoms. Beside blockade of the renin-angiotensin
      system, the angiotensin converting enzyme inhibitors act via the inhibition of
      bradykinin degradation which increase NO levels. Finally, vascular endothelial NO
      expression is improved by exercise training and participates in the improvement
      of exercise capacity in patients with chronic heart failure involved in cardiac
      readaptation program.

PMID- 11324317
TI  - [Clinical and biological investigation of NO].
AB  - Furchgott et al. demonstrated in 1980 that relaxation of arterial smooth muscle
      cells in response to acetylcholine is dependent on the integrity of endothelium.
      They named the factor responsible of this intercellular relationship EDRF
      (Endothelium Derived Relaxing Factor), which was identified 7 years latter as
      nitric oxide (NO), a free radical gas. In vessels, NO is generated locally by the
      endothelial NO synthase and its effect is mainly paracrine (relaxation of the
      underlying smooth muscle cells, and inhibition of platelet aggregation). The in
      vivo half-life of NO is short, and the assessment of its production is thus
      difficult. Invasive and non invasive techniques are now available to explore the
      variations of arterial diameter or flow. Furchgott's pioneering work anticipated
      the whole pathophysiology of endothelial-dependent relaxation. Indeed, numerous
      diseases, in particular atherosclerosis, are accompanied by abnormalities of
      endothelial-dependent vasodilation ("endothelial dysfunction"). Whereas
      acetylcholine (or serotonin) infused in a normal artery elicits a vasodilation,
      in contrast, it promotes a vasoconstriction in an atheromatous artery, as a
      consequence of a decrease in NO bioavailability. This defect in NO favors
      arterial spasm, interaction between platelets and arterial wall and thrombosis,
      and thus probably cardiovascular events. NO cannot be measured directly in
      humans, except in exhaled NO. In vivo, NO is rapidly oxidized in nitrite (NO2-)
      and in nitrate (NO3-), the summation being NOx. We shall detail the limitations
      of this measurement as a biochemical index of NO production from "endothelial"
      origin.

PMID- 11324318
TI  - [Regenerative potential in the organ of Corti after otic intoxication].
AB  - The auditory sensory cells are sensitive to a variety of influences such as
      noise, ototoxic drugs and aging. In the cochlea of mammals, the destroyed sensory
      cells are not replaced by new sensory cells. That leads to cochlear deafness, a
      frequent disease in human. Unfortunately, such auditory impairment is out of
      reach of treatment. The development of new therapeutic strategies in this field
      requires a precise knowledge of the mechanisms involved in auditory sensory cells
      disappearance and in organ of Corti's degeneration. The aim of our study was to
      characterize cellular and molecular changes in the cochlea of rats which had been
      intoxicated with the ototoxic antibiotic amikacin. The animals were sacrificed at
      different survival times during and after the antibiotic treatment and their
      cochleas were investigated using transmission and scanning electron microscopy
      and using confocal microscopy after tissue labellings with different fluorescent
      probes. The results revealed the existence of three periods. The first one
      corresponds to the disappearance of the sensory cells which die by apoptosis.
      During the second period, the organ of Corti undergoes a scarring process;
      concomitantly, a contingent of nonsensory supporting cells attempts to
      transdifferentiate directly into sensory cells. This process however fails, and
      the supporting cells never reach the status of hair cells. A general process of
      dedifferentiation of all the epithelial cells of the organ of Corti followed by a
      massive apoptosis of numerous epithelial cells and of most ganglion cells occurs
      during the third period. After that, the organ of Corti is definitely reduced to
      a simple monolayered epithelium. On the basis of these data, experimental
      strategies aimed i) to protect the sensory cells against apoptosis and ii) to
      promote sensory cell regeneration are now under study. They might have important
      implications in human therapy.

PMID- 11324319
TI  - [Circadian fluctuations in the muscular efficiency of athletes: with sleep versus
      sleep deprivation].
AB  - The influence of time of day on muscular performance was studied. From part of
      the results of two different studies (EAS et EPS), the effects of sleep
      deprivation were appreciated. Seven times over the 24-h period, developed torque
      and myoelectric activity were estimated during maximal isometric voluntary
      contractions using an isokinetic dynamometer: elbow flexion for EAS in
      standardised sleep, and knee extension for EPS in complete sleep deprivation. The
      results showed nycthemeral changes in torque in both conditions (p < 0.005), with
      maximal values recorded at the beginning of night. Although during sleep
      deprivation (EPS) the rhythm followed neurophysiological factors, during EAS,
      this rhythm was accounted for by the variations in the contractile state of
      muscle.

PMID- 11324320
TI  - [Effects of an eccentric exercise session short-term recovery of muscle
      contractility].
AB  - Short term effects of 5 sets of 10 maximal eccentric contractions of the elbow
      flexors, performed using an isokinetic ergometer, were studied. Maximal
      eccentric, isometric, concentric torque, myoelectrical activity of biceps and
      triceps brachii, voluntary activation, M-wave amplitude, as well as twitch and
      maximal contraction and relaxation velocities were measured before (Control), 2
      minutes after (Post), 24 hours (Post24 h) and 48 hours (Post48 h) after the
      exercise session. Torque significantly decreased over the recovery period,
      whatever the contraction type, excepted concentric torque assessed at 240
      degrees.s-1 which recovered its Control value at Post48 h. Activation level
      significantly decreased at Post (p < 0.05) and returned to its Control value at
      Post24 h. Twitch, as well as maximal contraction and relaxation velocities had
      significantly declined among the experimental procedure (p < 0.01). M-wave
      amplitude was not modified after the exercise. These results indicate that, over
      a 48 hour rest period, torque decrement following a maximal eccentric exercise
      session should mainly be due to a failure of the peripheral part of the
      neuromuscular system, and force recovery should closely be linked to the
      developed force value.

PMID- 11324321
TI  - [Biological functions of cyclooxygenase 2: control of its expression and
      activity].
AB  - Cyclooxygenase (COX) plays a pivotal role in the biosynthesis of prostanoids. The
      identification of an inducible isoform, COX-2, besides the constitutive one, COX
      1, suggested that the latter was dedicated to cytoprotection, whereas the former
      was responsible for inflammation and neoplasia. This oversimplification was
      amended due to the synthesis of new selective inhibitors of COX-2 and to the
      deletion of the COX-2 gene, which demonstrated the involvement of the inducible
      isoform in physiological as well as in pathological functions. Moreover, several
      reports describe effects of nonsteroidal anti-inflammatory drugs which do not
      result from the inhibition of COX activity.

PMID- 11324322
TI  - [Study of the behavior of the vegetative meristem of alfa (Stipa tenacissima L.).
      Cytological and histological approaches].
AB  - The biological and cytological studies of the vegetative meristem of Stipa
      tenacissima L. gave clear indication about its structure. It was similar to what
      was previously described in several species. This meristem showed an axial apical
      zone constituted by sommital cells of both tunica and corpus, a sub-apical
      lateral zone, very chromophilous, representing the initial ring and a medullar
      meristem. The cytofluorimetric determination of DNA in interphasic nuclei of
      these three zones revealed that the nuclei of the apical and lateral zones were
      in S phase, announcing the beginning of mitosis and meaning that these zones were
      the centers of the foliar initiation. The medullar meristem was in dormancy: all
      the nuclei were in G1 phase.

PMID- 11324323
TI  - Use of medical literature in lawsuits alleging medical negligence.

PMID- 11324324
TI  - Treatment of refractory angina pectoris by transmyocardial laser
      revascularization.
AB  - Mounting evidence that Transmyocardial Laser Revascularization (TMR) is a safe
      and effective treatment for angina arrives as an increasing number of patients
      having angioplasties and coronary artery bypass grafts experience failure with
      time. Like angioplasty and coronary bypass, TMR is in fact a palliative rather
      than a cure for atherosclerotic heart disease.

PMID- 11324325
TI  - Evidence-based practice. Guidelines for managing peripheral intravascular access
      devices.

PMID- 11324326
TI  - End the debate. Entry level into practice should be the master's degree.

PMID- 11324327
TI  - Surviving hospital restructuring. Next steps.

PMID- 11324328
TI  - Measuring role changes for nurses.

PMID- 11324329
TI  - Enhanced quality through creative problem solving.

PMID- 11324330
TI  - The nursing shortage revisioning the future.
AB  - A severe shortage of nurses is being experienced nationally and globally. In
      South Florida, one of the most severely impacted regions in the world, a group of
      healthcare organizations, educational institutions, and nursing organizations
      formed the Nursing Shortage Consortium to combat the nursing shortage. Strategic
      efforts to recruit and retain nurses are underway, with a focus on nurturing
      interest among young people and increasing opportunities to stimulate their
      interest, to increase the supply of appropriately prepared professional nurses.

PMID- 11324332
TI  - A comparison of governance types and patient satisfaction outcomes.
AB  - Given our dynamic healthcare marketplace, it is imperative to examine the context
      in which nurses function. A unit level study was conducted to investigate the
      influence of governance type on organizational culture, nurse work satisfaction,
      nurse retention, and patient satisfaction. The results of the study will be of
      value to nurse executives wanting to redesign the context for nursing service to
      improve outcomes, including nurse and patient satisfaction.

PMID- 11324331
TI  - Can nurses govern in a government agency?
AB  - A shared governance model was implemented within the nursing service of the
      Durham Veterans Affairs Medical Center in 1997. In 1999, members of the Nursing
      Quality/Staff Education/Research Council examined facility nurses' perceptions of
      governance to determine the degree to which the model had been implemented.
      Results of the study indicate that although imperatives at the organizational
      level were incompatible with three aspects of shared governance, there were three
      shared governance dimensions pertaining to basic nursing practice that reached or
      surpassed governance thresholds. This study highlights the potential of nursing
      management innovation within highly bureaucratic organizations.

PMID- 11324333
TI  - Outcomes of hospital restructuring and reengineering. How is success or failure
      being measured?
AB  - Healthcare has undergone tremendous changes during the last decade. In response
      to external forces, institutions and systems have sought to increase efficiency,
      decrease waste and duplication, and reshape the way that care is delivered. The
      authors describe the outcomes of restructuring and reengineering efforts in
      United States hospitals during the years 1997-1999. Internal hospital
      restructuring strategies, methods for evaluation, and unexpected outcomes are
      discussed as well as recommendations for future outcome evaluation.

PMID- 11324334
TI  - Factors influencing satisfaction and anticipated turnover for nurses in an
      academic medical center.
AB  - OBJECTIVES: The purpose of this study was to examine the relationships between
      work satisfaction, stress, age, cohesion, work schedule, and anticipated turnover
      in an academic medical center. BACKGROUND DATA: Nurse turnover is a costly
      problem that will continue as healthcare faces the impending nursing shortage, a
      new generation of nurses enter the workforce, and incentives provided to nurses
      to work for institutions increase. A variety of factors influence the retention
      of nurses in adult care settings, including work satisfaction, group cohesion,
      job stress, and work schedule. In general, previous research has documented
      positive relationships between work satisfaction, group cohesion, strong
      leadership, and retention rates and a negative relationship between stress, work
      schedule, and retention. In addition, age and experience in nursing are related
      to job satisfaction. METHODS: This study used a cross-sectional survey design in
      which nurses from 12 units in a 908-bed university hospital in the Southeast
      completed questionnaires on one occasion. The following factors were measured
      using self-report questionnaires: nurse perception of job stress, work
      satisfaction, group cohesion, and anticipated turnover. RESULTS: The more job
      stress, the lower group cohesion, the lower work satisfaction, and the higher the
      anticipated turnover. The higher the work satisfaction, the higher group cohesion
      and the lower anticipated turnover. The more stable the work schedule, the less
      work-related stress, the lower anticipated turnover, the higher group cohesion,
      and the higher work satisfaction. Job Stress, work satisfaction, group cohesion,
      and weekend overtime were all predictors of anticipated turnover. There are
      differences in the factors predicting anticipated turnover for different age
      groups. CONCLUSIONS: As healthcare institutions face a nursing shortage and a new
      generation of nurses enter the workforce, consideration of the factors that
      influence turnover is essential to creating a working environment that retains
      the nurse.

PMID- 11324335
TI  - Interfacing a silicon chip to pairs of snail neurons connected by electrical
      synapses.
AB  - Future hybrid neuron-semiconductor chips will consist of complex neural networks
      that are directly interfaced to electronic integrated circuits. They will help us
      to understand the dynamics of neuronal networks and may lead to novel
      computational facilities. Here we report on an elementary step towards such
      neurochips. We designed and fabricated a silicon chip for multiple two-way
      interfacing, and cultured on it pairs of neurons from the pedal ganglia of the
      snail Lymnaea stagnalis. These neurons were joined to each other by an electrical
      synapse, and to the chip by a capacitive stimulator and a recording transistor.
      We obtained a set of neuroelectronic units with sequential and parallel signal
      transmission through the neuron-silicon interface and the synapse, with a
      bidirectionally interfaced neuron-pair and with a signal path from the chip
      through a synaptically connected neuron pair back to the chip. The prospects for
      assembling more involved hybrid networks on the basis of these neuroelectronic
      units are considered.

PMID- 11324336
TI  - Recognition of partly occluded patterns: a neural network model.
AB  - Human beings are often able to read a letter or word partly occluded by
      contaminating ink stains. However, if the stains are completely erased and the
      occluded areas of the letter are changed to white, we usually have difficulty in
      reading the letter. In this article I propose a hypothesis explaining why a
      pattern is easier to recognize when it is occluded by visible objects than by
      invisible opaque objects. A neural network model is constructed based on this
      hypothesis. The visual system extracts various visual features from the input
      pattern and then attempts to recognize it. If the occluding objects are not
      visible, the visual system will have difficulty in distinguishing which features
      are relevant to the original pattern and which are newly generated by the
      occlusion. If the occluding objects are visible, however, the visual system can
      easily discriminate between relevant and irrelevant features and recognize the
      occluded pattern correctly. The proposed model is an extended version of the
      neocognitron model. The activity of the feature-extracting cells whose receptive
      fields cover the occluding objects is suppressed in an early stage of the
      hierarchical network. Since the irrelevant features generated by the occlusion
      are thus eliminated, the model can recognize occluded patterns correctly,
      provided the occlusion is not so large as to prevent recognition even by human
      beings.

PMID- 11324337
TI  - Simulation of gait and gait initiation associated with body oscillating behavior
      in the gravity environment on the moon, mars and Phobos.
AB  - A double-inverted pendulum model of body oscillations in the frontal plane during
      stepping [Breniere and Ribreau (1998) Biol Cybern 79: 337-345] proposed an
      equivalent model for studying the body oscillating behavior induced by step
      frequency in the form of: (1) a kinetic body parameter, the natural body
      frequency (NBF), which contains gravity and which is invariable for humans, (2) a
      parametric function of frequency, whose parameter is the NBF, which explicates
      the amplitude ratio of center of mass to center of foot pressure oscillation, and
      (3) a function of frequency which simulates the equivalent torque necessary for
      the control of the head-arms-trunk segment oscillations. Here, this equivalent
      model is used to simulate the duration of gait initiation, i.e., the duration
      necessary to initiate and execute the first step of gait in subgravity, as well
      as to calculate the step frequencies that would impose the same minimum and
      maximum amplitudes of the oscillating responses of the body center of mass,
      whatever the gravity value. In particular, this simulation is tested under the
      subgravity conditions of the Moon, Mars, and Phobos, where gravity is 1/6, 3/8,
      and 1/1600 times that on the Earth, respectively. More generally, the simulation
      allows us to establish and discuss the conditions for gait adaptability that
      result from the biomechanical constraints particular to each gravity system.

PMID- 11324338
TI  - Behavioural and physical reactions of the Colorado potato beetle, Leptinotarsa
      decemlineata (Say) (Coleoptera: Chrysomelidae) walking on a slanted surface.
AB  - A natural reaction of the adult Colorado potato beetle [Leptinotarsa decemlineata
      (Say)] is to walk uphill on sloped surfaces. The geotaxis reaction of the beetle
      was observed on slopes of 20 degrees or steeper. It was demonstrated that the
      uphill orientation behaviour was not a consequence of physical limitation for
      across-slope locomotion. The walking speed of insects deviating from the fall
      line did not change within the range of slope angles tested. The speed of adult
      beetles decreased with an increase in the slope of the substrate as a reaction to
      the increased gravitational force vector opposing uphill movement. The larger
      size of the hind legs might make uphill locomotion more efficient than traversing
      a sloped surface. As the angle of the slope increased, the gait changed from a
      3/3 to a 5/1, as did the posterior and anterior extreme position of the legs.
      This behaviour might be triggered by the need to maintain balance on slanted
      surfaces as the vertical projection of the centre of mass on the substrate moved
      outside the support base pattern at the steeper angles. In one experiment beetles
      were made to pull a load when walking over a horizontal surface. The loads pulled
      were equivalent to the gravitational loads opposing forward motion when walking
      up a slope. No differences in forward speed or gait were observed at the lower
      angle equivalent compared to beetles walking on slopes. Differences in speed were
      noted at slope angles higher than 40 degrees indicating that adaptation of the
      walking strategy might be needed on steeply slanted surfaces.

PMID- 11324339
TI  - A thalamo-cortical model of the executive attention system.
AB  - In a previous paper [Kilmer (1996) Neural Netw 9: 567-573] we developed a
      differential equation model of how a stable focus of attention could be
      maintained in a higher mammalian brain. The so-called TRC model consisted of
      interconnected modules, with each module comprised of a simple representations of
      parts of the reticular thalamic nucleus, specific thalamic nuclei, nonspecific
      thalamic nuclei, and cortex, together with the known excitatory and inhibitory
      interconnections between them. TRC was analyzed only for steady states under zero
      inputs. Here we analyze the behavior of TRC_2, a substantially modified and
      reinterpreted TRC, for steady attention and attention-switching behavior under
      nonzero inputs. We show that TRC_2 always converges to a unique mode of primary
      attention, and that it allows concurrently one or more other modes of weak
      attention, which experience suggests occurs often. A crucial postulate for TRC_2
      is that a mode alpha does not actively compete against other modes unless primary
      attention is paid to mode alpha. This postulate should be testable
      experimentally.

PMID- 11324340
TI  - Wavelet entropy in event-related potentials: a new method shows ordering of EEG
      oscillations.
AB  - In this work we show the application of a measure of entropy defined from the
      wavelet transform, namely the wavelet entropy (WS), to the study of event-related
      potentials (ERPs). WS was computed for ERPs recorded from nine healthy subjects
      with three different types of stimuli, among them target stimuli in a cognitive
      task. A significant decrease of entropy was correlated with the responses to
      target stimuli (P300), thus showing that these responses correspond to a more
      "ordered" state than the spontaneous EEG. Furthermore, we propose the WS as a
      quantitative measure for such transitions between EEG ("disordered state") and
      ERP ("ordered state").

PMID- 11324341
TI  - Myelin as longitudinal conductor: a multi-layered model of the myelinated human
      motor nerve fibre.
AB  - The myelin sheath is normally regarded as an electrical insulator. Low values of
      radial conductance and capacitance have been measured, and in electrical models
      of myelinated axons the contribution of longitudinal conduction within the sheath
      has been ignored. According to X-ray diffraction studies, however, myelin sheaths
      comprise alternate lipid and aqueous layers, and the latter may be expected to
      have a low resistivity. We propose a new model of myelinated axons in which the
      aqueous layers within the myelin provide appreciable longitudinal and radial
      conductance, the latter via a spiral pathway. We have investigated the likely
      contribution of these conductive paths within the myelin to the electrical
      properties of a human motor nerve fibre by computer simulation, representing the
      myelin sheath as a series of interconnecting parallel lamellae. With this new
      model, action potential conduction has been simulated along a 20-node cable, and
      the electrotonic responses to 100-ms depolarizing and hyperpolarizing current
      pulses have been simulated for a uniformly polarized fibre. We have found that
      the hypothesis of a longitudinally conducting myelin sheath improves our previous
      model in two ways: it is no longer necessary to make implausible assumptions
      about the resistivity or width of the periaxonal space to simulate realistic
      electrotonus, and the conduction velocity is appreciably faster (by 8.6%).

PMID- 11324342
TI  - Variability of the electric organ discharge interval duration in resting Gymnotus
      carapo.
AB  - We recorded the electric organ discharges of resting Gymnotus carapo specimens.
      We analyzed the time series formed by the sequence of interdischarge intervals.
      Nonlinear prediction, false nearest neighbor analyses, and comparison between the
      performance of nonlinear and linear autoregressive models fitted to the data
      indicated that nonlinear correlations between intervals were absent, or were
      present to a minor extent only. Following these analyses, we showed that linear
      autoregressive models with combined Gaussian and shot noise reproduced the
      variability and correlations of the resting discharge pattern. We discuss the
      implications of our findings for the mechanisms underlying the timing of electric
      organ discharge generation. We also argue that autoregressive models can be used
      to evaluate the changes arising during a wide variety of behaviors, such as the
      modification in the discharge intervals during interaction between fish pairs.

PMID- 11324343
TI  - [Cardiopulmonary resuscitation--new wine in old bottles].

PMID- 11324344
TI  - [Treatment for acute renal failure--concepts and controversies. 1. Pharmacologic
      treatment and experimental strategies].
AB  - Acute renal failure is the common result of various damaging mechanisms.
      Prophylaxis and differentiated therapy of acute renal failure are of outmost
      importance in anaesthesiology and intensive care medicine. The efficiency of
      pharmacotherapy is narrowly limited. Diuretics increase the urine output, but
      they do neither ameliorate the clinical course of the patient nor the prognosis
      of established acute renal failure. Dopamine and natriuretic peptides have no use
      in prevention and treatment of acute renal failure. Calcium-channel-blockers are
      valuable in cadaveric kidney transplantation. Osmodiuretics prevent intratubular
      precipitation of hemoglobin and myoglobin crystals; they also have some value in
      cadaveric kidney transplantation. Experimental studies investigated the
      possibility to enhance the regeneration of the tubular epithelial cell. Whereas
      in vitro studies and studies in animal models using various growth factors
      yielded promising results, these could not be reproduced in patients with acute
      renal failure. The physiology of NO in the kidney is incompletely understood.
      Actual progress is made in the understanding of lipid peroxidation and potential
      pharmacological implications. The mainstay for the assurance of high-quality
      patient care remain a vigilant identification of the patient at risk and an
      arduous search to avoid nephrotoxic substances and situations implicating
      potential renal damage.

PMID- 11324345
TI  - [Are there certified indications for the use of antithrombin III in intensive
      care].
AB  - The serine-protease-inhibitor antithrombin III (AT III) has often been
      recommended for the therapy of septic patients as it provides anticoagulant and
      antiinflammatory actions. In animal studies the prophylactic treatment with AT
      III in a dose > 250 U/kg prevented the development of disseminated intravascular
      coagulopathy and vital organ dysfunction during sepsis and lowered the mortality
      rate. In clinical studies with septic patients therapy usually was started
      several hours after the start of the disease in dosages much lower than those
      used in animal studies. In these patients AT III-therapy improved laboratory
      changes of disseminated intravascular coagulopathy but was unable to lower the
      mortality rate. Hereditary AT III deficiency, lack of heparin effect due to low
      AT III levels, disseminated intravascular coagulation disorders are indications
      for the use of AT III while beneficial effects of AT III in patients suffering
      from SIRS, sepsis or septic shock have not yet been demonstrated.

PMID- 11324346
TI  - [CPR--guidelines 2000. New international guidelines for cardiopulmonary
      resuscitation].
AB  - The "Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency
      Cardiovascular Care. An International Consensus an Science" are the first true
      international CPR guidelines in the history of resuscitation medicine. Experts
      from major international resuscitation organizations (International Liaison
      Committee on Resuscitation, ILCOR) achieved a consensus of recommendations which
      had to pass a rigorous review procedure applying the tools of evidence-based
      medicine: all proposed guidelines or guideline changes had to be based on
      critically appraised pieces of evidence which had to be integrated into a final
      class of recommendations. The most important changes compared to previous
      recommendations from either the European Resuscitation Council or the American
      Heart Association are presented and commented upon.

PMID- 11324347
TI  - [On-scene helicopter transport at night].
AB  - Air medical rescue services at night are associated with an increased risk for
      life and health of the helicopter crew. They are not allowed in all federal
      states of Germany and only a few bases provide this service. The advantage of
      short transportation times by air cannot be achieved at night due to a flight
      preparation phase of at least 30 minutes until lift-off. Two case reports
      demonstrate that requests for helicopters at night may even lead to a
      transportation associated delay of treatment because of the time until the
      helicopter arrives on-scene. Thus emergency physicians have to know the
      possibilities and limitations of helicopter emergency medical services at night.

PMID- 11324348
TI  - [Removal of lepirudin used as an anticoagulant in mechanical autotransfusion with
      Cell-Saver 5].
AB  - Former studies demonstrated that small amounts of heparin might remain in the
      prepared retransfusion blood during intraoperative autotransfusion. This could
      lead to serious complications in patients suffering from heparin-induced
      thrombocytopenia type II (HIT II). Lepirudin is an approved anticoagulant in HIT
      II-patients. We studied to what extent lepirudin is washed out during the
      preparation of retransfusion blood, when it is used as anticoagulant for the
      autotransfusion device cell saver 5. METHODS: We investigated four different
      concentrations of lepirudin solutions, 5 mg, 10 mg, 20 mg and 30 mg per litre
      normal saline. In order to imitate a clinical situation, each lepirudin solution
      was mixed with human blood in a 1:5-ratio and put into the reservoir of the cell
      saver. The device was started in the automatic mode using 1000 ml saline as
      washing solution. Several runs were carried out (five times using the 5 mg/l
      solution, ten times the 10 mg/l, eleven times the 20 mg/l and eleven times the 30
      mg/l solution). The lepirudin concentration in the prepared retransfusion blood
      was measured. RESULTS: The median percentage reduction of the lepirudin content
      from the reservoir blood to the retransfusion blood was 100% for the 5 mg/l,
      90.4% for the 10 mg/l, 94.3% for the 20 mg/l and 86.3% for the 30 mg/l solution.
      The differences of percentage reduction are not significant. But the different
      lepirudin concentrations in the anticoagulant solution have a significant
      influence on the lepirudin concentration in the retransfusion blood. The
      lepirudin concentration (median) in the retransfusion blood was 0.00 microgram/ml
      for the 5 mg/l, 0.16 microgram/ml for the 10 mg/l, 0.19 microgram/ml for the 20
      mg/l and 0.66 microgram/l for the 30 mg/l lepirudin solution. CONCLUSION:
      Lepirudin as an anticoagulant for intraoperative autotransfusion is effectively
      eliminated using the cell saver 5 device in the automatic mode with 1000 ml
      saline as washing solution. A clinically relevant disturbance of coagulation is
      not to be expected, even if the highest concentration of lepirudin anticoagulant
      solution investigated in this study is used.

PMID- 11324349
TI  - Pharmacology--neurophysiology clinical aspects.

PMID- 11324350
TI  - [Important and new aspects on the toxicology and pharmacology of local
      anesthetics].

PMID- 11324351
TI  - [Postoperative cognitive dysfunction in geriatric patients].

PMID- 11324352
TI  - [New scientific findings on peripheral opioid receptors].

PMID- 11324353
TI  - [Effectiveness and cost-benefit ratio of regional anesthesia procedures].

PMID- 11324354
TI  - [Use of regional anesthesia in vascular surgery].

PMID- 11324355
TI  - [A patient with nodal tachycardia after general anesthesia during medication with
      a selective serotonin reuptake inhibitor].
AB  - We report on a 62 year old female patient treated with paroxetine, a selective
      serotonin reuptake inhibitor, because of an anxiety neurosis undergoing a vaginal
      hysterectomy in general anesthesia. Apart from a dietary treated diabetes
      mellitus there were no other diseases. There were no complications during the
      operation. At the end of the anesthesia an A-V nodal tachycardia appeared which
      spontaneously changed to a sinus rhythm ten hours after the end of the operation.
      No clinical or laboratory findings indicated a cardiac ischemia and an additional
      Holter ECG-Recording showed no further cardiac arrhythmias. No other
      complications occurred afterwards and the patient was discharged after two weeks.
      This case report demonstrates clearly that despite a reduced rate of
      cardiovascular complications compared to other types of antidepressants selective
      serotonin reuptake inhibitors can lead to perioperative cardiac arrhythmias.

PMID- 11324356
TI  - A critical review of cost reduction in neonatal intensive care. I. The structure
      of costs.
AB  - Neonatal intensive care is expensive. In the current era of intense cost
      containment in hospital care, neonatologists and hospital administrators are
      under intense pressure to find strategies for cost reduction for neonatal
      services. Few neonatal clinicians are trained in economics, management, or
      accounting, and few hospital administrators are familiar with neonatal intensive
      care. In this review, we describe the structure and sources of hospital costs and
      the accounting systems needed to isolate and measure such costs. We discuss where
      efficiencies might be found and consider specific issues in capitated settings
      such as health maintenance organizations in the United States, the Canadian
      health care system and the National Health System in the United Kingdom.

PMID- 11324357
TI  - The advantages of prenatal consultation by a neonatologist.
AB  - The neonatologist can be a valuable source of information for the pregnant woman
      and her partner faced with making difficult decisions. In specific clinical
      situations, a focused, thorough consultation by a neonatologist provides benefits
      for the parents, their child, the physicians, and the health care delivery system
      as a whole. Members of the perinatal team should act to facilitate early neonatal
      consultation in order to ease the transition from the obstetric to the neonatal
      team after delivery.

PMID- 11324358
TI  - A critical review of cost reduction in neonatal intensive care. II. Strategies
      for reduction.
AB  - Neonatal intensive care is extremely expensive; there is both a financial and an
      ethical obligation to practice efficiently. In the current era of intense cost
      containment in hospital care, neonatologists and hospital administrators are
      under pressure to find strategies for cost reduction for neonatal services. In
      this review, we address reducing discretionary admissions, the high costs of low
      cost testing, minimizing use of selected high-cost technologies (ventilators and
      parenteral nutrition), shortening length of stay, and optimizing nursing
      allocation.

PMID- 11324359
TI  - Persistence of Plasmodium falciparum in the placenta after apparently effective
      quinidine/clindamycin therapy.
AB  - The persistence of Plasmodium falciparum in the placenta after apparently
      adequate therapy with quinine has been described. We describe this phenomenon in
      the placenta of a 19-year-old woman with falciparum malaria, who was treated with
      a combination of quinidine and clindamycin. Although this therapy was effective
      and diminished her peripheral blood parasitemia from 3% at presentation to almost
      undetectable at the time of delivery, vast numbers of P. falciparum-infected
      erythrocytes were present in the maternal sinusoids of the placenta. This
      sequestration of infected erythrocytes produced a local parasitemia in the
      placenta of 70% to 80%. Additionally, rare Plasmodium-infected erythrocytes were
      also seen in the fetal blood of the placenta. We review malaria in pregnancy,
      parasitic involvement of the placenta and emphasize that Plasmodium-infected
      erythrocytes may persist in the placenta even after clearance of parasites from
      the peripheral blood.

PMID- 11324360
TI  - Abnormal cry and intracranial calcifications: clues to the diagnosis of fetal
      varicella-zoster syndrome.

PMID- 11324361
TI  - Venous gangrene of lower extremities and Staphylococcus aureus sepsis.
AB  - This is a study of the venous gangrene of lower extremities and Staphylococcus
      aureus sepsis. We report on a premature infant who developed phlegmasia cerulea
      dolens (PCD) in both lower extremities in association with S. aureus sepsis,
      resulting in gangrene of the right foot. Non-pitting edema and cyanosis of the
      digits of the right lower extremity were noted 48 hours after hypotension and
      severe shock due to S. aureus sepsis. Intravenous antibiotics, isotonic fluids,
      and heparin were administered. Twenty-four hours later, edema and ischemic
      changes of the first and fifth left toes were also noted. Doppler flow study
      showed flow signals in both right and left popliteal arteries. However, there
      were no Doppler signals in neither right nor left popliteal vein. Emergency
      fasciotomies were performed on both lower limbs. The progression of the gangrene
      was limited to the right foot. There was complete resolution of PCD in both lower
      extremities. To the best of our knowledge, the association of S. aureus sepsis
      with PCD and venous gangrene in an infant has not been reported previously. This
      case illustrates the need for early recognition of PCD and aggressive
      intervention.

PMID- 11324362
TI  - Congenital varicella-zoster virus infection after maternal subclinical infection:
      clinical and neuropathological findings.
AB  - OBJECTIVE: It is known that varicella-zoster virus (VZV) can cause asymptomatic
      infections, but it has not been described that congenital infection can be caused
      by maternal subclinical infection. The purpose of this study is to evaluate
      clinical and neuropathologic findings of infants with neonatal seizures and
      cerebrospinal fluid (CSF) VZV antibodies, but no maternal clinical VZV infection
      during the pregnancy. STUDY DESIGN: Screening of 201 neonates were studied for
      congenital viral infections, because of neurologic problems of unknown origin.
      Antibodies to 16 different microbes were investigated from the CSF and the serum
      of the neonates, as well as from the first trimester and postpartum serum of
      their mothers. Clinical symptoms and signs as well as neuropathology of those
      infants with antibodies to VZV in CSF were evaluated in this study. RESULTS: Four
      neonates with antibodies to VZV in CSF were identified and CSF findings were
      reported earlier. Their mothers had laboratory evidence of infection, based on a
      significant rise in serum VZV antibody level during pregnancy in three mothers,
      and a constantly high antibody level to VZV in one mother. All four children had
      seizures and abnormalities in muscular tone during the neonatal period, but no
      typical manifestations of a congenital VZV infection. One child died at the age
      of 4 months. At autopsy, neuropathologic examination showed foci of astrocytic
      hyperplasia and hypertrophy but no specific signs of viral infection. CONCLUSION:
      Maternal subclinical VZV infection can cause congenital infection with neurologic
      symptoms and signs in the child.

PMID- 11324363
TI  - Special imaging casebook. Pentalogy of Cantrell.

PMID- 11324364
TI  - Placental pathology casebook. Unusually large acardiac twin pregnancy at term.

PMID- 11324365
TI  - Effect of sleep position on apnea and bradycardia in high-risk infants.
AB  - OBJECTIVE: The purpose of this investigation was to investigate, in high-risk
      infants, the occurrence of abnormalities in documented monitor downloads during
      the side versus prone position. STUDY DESIGN: Forty infants admitted to the A. I.
      duPont Hospital for Children with diagnoses associated with sudden infant death
      syndrome were included in this investigation. During an overnight
      hospitalization, infants were placed on home apnea monitors, with computer memory
      to capture alarms for apnea > 20 seconds, age-defined bradycardia, and
      tachycardia. Infants were studied for 12 hours. Each infant was assigned to 6
      hours of prone and side during the 12-hour period, with order of position
      randomly assigned by random number generation. Differences between the two
      positions in alarm frequency and significant events, as determined by a blinded
      interpreting physician were analyzed by Fisher exact test, with p < 0.05. Power
      analysis necessitated 20 patients in each group, with beta error of 0.2. RESULTS:
      Eleven episodes of apnea occurred in the prone position, and 16 in the side
      position (p = NS). The mean numbers of apnea events per tracing in the prone
      position was 0.27 +/- 0.84 and 0.39 +/- 1.1 in the side position (p = 0.58). The
      mean number of bradycardia events per tracing in the prone position was 0.44 +/-
      1.45 and 0.49 +/- 1.94 in the side position (p = 0.9). CONCLUSION: Clinicians
      need to be cautious when recommending the side or prone position in this group of
      high-risk infants. The results in this investigation provide support for the Back
      to Sleep Campaign recommendations to be applied, not only to healthy term
      infants, but higher risk infants as well. Studies of the high-risk infant in the
      supine position are warranted.

PMID- 11324366
TI  - Demographic and intrapartum characteristics of term pregnancies with early-onset
      neonatal seizures.
AB  - OBJECTIVE: To compare the demographic and intrapartum factors of term pregnancies
      in which early-onset neonatal seizures developed with the characteristics of a
      large, unselected control population. STUDY DESIGN: Pregnancies delivered at term
      (gestational age > or = 37 weeks) in one birthing unit between 1984 and 1995 with
      a discharge diagnosis of neonatal seizures were identified. Maternal and neonatal
      charts of these patients were reviewed to confirm the diagnosis of early-onset
      seizure (EOS) which was defined as a clinical or EEG-diagnosed seizure within 72
      hours of life. Demographic and intrapartum factors were compared between these
      EOS cases and all singleton term pregnancies delivered over the same time period
      in which there was no EOS. A regression model was then developed to determine
      factors predictive of EOS. RESULTS: Of 80,561 total deliveries during the 11-year
      study period, there were 64,340 control and 62 EOS (0.1%) deliveries. Regression
      modeling identified NICU admission, depressed 1- and 5-minute Apgar scores, and
      neonatal intubation as predictors of EOS, but not operative vaginal, vaginal
      breech, or cesarean delivery. CONCLUSION: Depressed condition at birth and/or the
      requirement for NICU care was the most important risk associated with early
      seizures in term infants.

PMID- 11324367
TI  - Physicians who induce labor for fetal macrosomia do not reduce cesarean delivery
      rates.
AB  - OBJECTIVE: To determine whether obstetricians with high rates of induction for
      the indication of fetal macrosomia had higher or lower cesarean section rates.
      STUDY DESIGN: Data were analyzed from 1432 deliveries with birthweights > 4000 g.
      Four physician populations were identified: a faculty service and three groups of
      private practitioners with induction rates 20% to 40%, 40% to 60% and > 60%. The
      average cesarean section rate was determined for each group as well as the
      percentage of each group's deliveries occurring before 39 weeks, at 39, at 40,
      and after 40 weeks. In addition, the relative risk of cesarean delivery was
      calculated for the entire study population. RESULTS: No correlation was found
      between the rate of induction of labor and the rate of cesarean section. Delivery
      of nulliparous and multiparous patients after 40 weeks carried an increased risk
      of cesarean section. Delivery of multiparous patients before 39 weeks did also.
      Obstetricians with induction rates > 40% significantly decreased the incidence of
      delivery after 40 weeks, which lowered their cesarean section rates, but no net
      lowering occurred because of increased rate of cesarean section < 39 weeks.
      CONCLUSION: A fetal weight of 4000 g or more is not an indication for induction
      of labor. For multiparous patients, induction at 38 weeks or before is associated
      with an increased rate of cesarean delivery.

PMID- 11324368
TI  - Nursery survival for infants of birth weight 500-1500 grams during 1982-1995.
AB  - OBJECTIVE: To evaluate nursery survival of very low birth weight infants (VLBW)
      over time, born in the same large inner-city hospital with a predominantly
      Hispanic population. METHODS: All liveborn VLBW infants weighing 500-1500 g at
      birth were included in four time periods of 2 years' duration during 1982 to
      1995. Demographics were collected for the obstetric population. Clinical data
      were collected including maternal and infant perinatal factors. All infants were
      assigned a cause of death and infants dying with lethal anomalies were then
      excluded from further evaluations. RESULTS: Overall survival improved
      progressively (p = 0.0001) with dramatic improvement in survival of infants 500
      750 g birth weight (BW) in period 4 (1994-1995). The number of lethal anomalies
      did not increase but accounted for a larger portion of deaths in period 4.
      Decreases in other causes of death over time reflected changes in perinatal care.
      Although the mothers were high-risk, none of the maternal factors evaluated
      showed any consistent effect on infant survival. Improved labor and delivery care
      was associated with improvement in Apgar scores, a decrease in intracranial
      hemorrhage/intraventricular hemorrhage as a cause of death and an improvement in
      survival between the first two periods. In spite of the increase in Cesarean
      sections for infants of 500-750 g BW and their improved survival in period 4, no
      clear advantage for Cesarean section could be demonstrated. The marked
      improvement seen in period 4 was associated with three changes in care: increased
      use of maternal steroids, administration of surfactant, and the use of newer
      ventilatory methods including high-frequency oscillatory ventilation. Although
      female gender has been reported to confer a protective influence for survival,
      this was not found in the final period. Black mothers comprised only about 2.5%
      of the total obstetric population but delivered approximately 10% of the VLBW
      infants. Despite the increased incidence of small for gestational age (SGA) among
      black infants, there were no differences in survival between blacks and
      Hispanics. Mean birth weight and gestational age in both survivors and
      nonsurvivors decreased significantly over the four time periods. In period 4, 50%
      survival occurred at a birth weight of 600-700 g and a gestational age of 23
      weeks. CONCLUSION: Nursery survival improved throughout the period of the study
      from 1982 to 1995 but especially during period 4 (1994-1995). Improved survival
      was associated with changes in both maternal and infant care. In infants of BW
      500-750 g, gestational age rather than birth weight was more closely associated
      with survival.

PMID- 11324369
TI  - Cardiovascular risk factors: distribution and prevalence in a rural population of
      Bangladesh.
AB  - BACKGROUND: Little is known about the cardiovascular risk factors in the
      Bangladeshi population. We examined 'classic' risk factors, including central
      obesity, in a rural population. METHODS: Non-biochemical variables were examined
      in 238 men and 272 women aged 18 years or more (mean +/- standard deviation 38.1
      +/- 10.7 years in men and 36.0 +/- 9.8 in women). Fasting blood glucose and total
      cholesterol concentrations were determined in a sub-sample of 106 men and 135
      women. RESULTS: Men and women had a similar body mass index (20.4 +/- 3.1 vs 20.8
      +/- 3.4 kg/m2), waist circumference (72.8 +/- 7.6 vs 71.4 +/- 8.7 cm), systolic
      blood pressure (118.4 +/- 13.7 vs 119.5 +/- 17.7 mmHg), diastolic blood pressure
      (75.9 +/- 9.9 vs 74.6 +/- 11.5 mmHg), total cholesterol (155.7 +/- 36.0 vs 162.0
      +/- 35.2 mg/dl) and blood glucose level (89.0 +/- 14.9 vs 86.2 +/- 9.6 mg/dl.
      After categorization of these variables, the prevalence of thinness (body mass
      index < 18.5; 30.0 vs 30.3%), obesity (body mass index > or = 30; 0.8 vs 1.1%),
      hypertension (systolic blood pressure > or = 140 and/or diastolic blood pressure
      > or = 90 or medication; 9.8 vs 15.6%), hypercholesterolemia (total cholesterol >
      or = 240; 2.8 vs 3.0%) and diabetes mellitus (blood glucose > or = 126; 2.9 vs
      0.7%) remained similar between the sexes. However, central obesity (waist
      circumference > or = 94 cm in men and > or = 80 cm in women) was less frequent
      (2.9 vs 16.8%; P = 0.001) in men. Overall, tobacco consumption (57.1 vs 23.2%; P
      = 0.001) and smoking (50.3% vs 2.9%; P = 0.001) were more frequent in men, but
      chewing tobacco consumption was similar (16.3 vs 21.4%; P = 0.095). CONCLUSIONS:
      Our sample size is small, and larger studies are necessary for a more accurate
      description of the risk factors.

PMID- 11324370
TI  - The duration of the association between serum cholesterol and coronary mortality:
      a 35-year experience.
AB  - OBJECTIVE: Our purpose was to study the time-related association between a single
      measurement of total serum cholesterol and the occurrence of coronary deaths in a
      population sample of middle-aged men. DESIGN: This is a longitudinal population
      study with multiple measurements of serum cholesterol and a 35-year follow-up for
      coronary mortality in 1622 coronary disease-free men aged 40-59 years belonging
      to the Italian rural cohorts of the Seven Countries Study. METHOD: A single
      measurement of serum cholesterol (plus those of five other risk factors as
      possible confounders) was considered. During 35 years of follow-up, 214 men died
      from coronary heart disease. Annual partitioned proportional hazards models were
      solved, one for each independent year of follow-up, to predict the risk of
      coronary heart disease deaths. Single-year hazard functions were cumulated and
      smoothed. Similar analyses were made starting from cholesterol measurements taken
      at years 5, 10 and 20 of follow-up. RESULTS: The resulting hazard curves showed
      regularly increasing risk for coronary events and fitted straight lines with
      large correlation coefficients, demonstrating a strong association of serum
      cholesterol with both early and late events. The slopes were steeper for
      cholesterol measurements taken at younger ages. The slope for cholesterol
      measurement taken at year 20 (age 60-84 years) was flat. In slopes starting at an
      early age, two components could be isolated corresponding to different
      associations with events (stronger for early events when measurements were taken
      around the age of 50 years and for late events when measurements were taken
      around the age of 55 or 60 years). CONCLUSION: A single measurement of total
      serum cholesterol in middle-aged men maintains a relatively monotone relationship
      with the occurrence of coronary heart disease deaths over 35 years. In the study
      population, measurements taken in late adulthood had smaller or null association
      with coronary disease deaths.

PMID- 11324371
TI  - Factor VII levels in patients undergoing coronary angiography: factor VII and
      coronary artery disease.
AB  - BACKGROUND: Factor VII (F VII) has been widely investigated as a risk factor for
      coronary atherosclerosis, however there is still debate about its role in the
      progression of coronary artery disease (CAD). In this study F VII levels were
      measured in patients with angiographically proven CAD and its relation with
      disease severity, coronary events and with other risk factors of coronary
      atherosclerosis were examined. METHODS: Consecutive patients referred to coronary
      angiography were divided in three groups: 1. CAD group--those with a significant
      lesion in one or more coronary arteries (n = 155), 2. High-risk group--patients
      with normal coronary arteries and with two or more risk factors (n = 54), 3.
      Controls--patients with normal coronary arteries and with no or one risk factor
      (n = 90). CAD group was also studied according to the number of vessels involved
      and to the history of coronary events. RESULTS: Mean F VII levels were not
      different between the three groups of patients. In CAD group, F VII increased
      parallel to the number of vessels involved (one vessel disease: 85 +/- 20%, two
      vessel disease: 92 +/- 23%, three vessel disease: 105 +/- 23%). Patients with a
      history of coronary events had significantly higher F VII levels than those
      without such a history (96 +/- 25% versus 89 +/- 22% respectively, P = 0.02).
      However, logistic regression analysis revealed no significant relation between F
      VII and either the presence of CAD or coronary events. CONCLUSIONS: F VII levels
      increase in patients with previous coronary events, but it is not an independent
      risk factor for the progression or for the severity of CAD.

PMID- 11324372
TI  - Effects of fluvastatin on cardiac events in renal transplant patients: ALERT
      (Assessment of Lescol in Renal Transplantation) study design and baseline data.
AB  - BACKGROUND: Recent clinical trials of primary and secondary prevention of
      cardiovascular disease have demonstrated that lowering plasma cholesterol with 3
      hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors ('statins')
      reduces morbidity and mortality from coronary heart disease in diverse patient
      populations. STUDY AIMS: The aim of the present ALERT (Assessment of Lescol in
      Renal Transplantation) study is to determine whether renal transplant recipients
      would also benefit from statin therapy. ALERT is a multicentre, randomized,
      double-blind, placebo-controlled trial to assess the effect of fluvastatin in
      renal transplant recipients with mild-to-moderate hypercholesterolaemia. The
      primary objective is to investigate the effects of fluvastatin on major adverse
      cardiac events (MACE). In addition, the effects on cardiovascular and all-cause
      mortality, as well as renal function, will be addressed. STUDY POPULATION: The
      study population contains patients with functioning renal allografts of more than
      6 months' duration, recruited from 75 centres in Northern Europe and Canada.
      Patients of both sexes, aged 30-75 years, with a total cholesterol level of 4.0
      9.0 mmol/l (155-348 mg/dl) were included, except for those with a history of
      myocardial infarction, where the upper limit for inclusion was 7.0 mmol/l (270
      mg/dl). STUDY DESIGN: A total of 2100 patients were recruited by the end of
      October 1997 and will be followed for up to 6 years. This report presents the
      design features of the study (recruitment, follow-up, sample size, data analysis
      and study organization), along with baseline results. ALERT is the first large
      scale prospective, randomized, double-blind study to address the prevention of
      cardiovascular mortality in renal transplant patients receiving an HMGCoA
      reductase inhibitor.

PMID- 11324373
TI  - Risk factors in established coronary heart disease: evaluation of a secondary
      prevention programme.
AB  - BACKGROUND: Coronary heart disease (CHD) is the leading cause of death in the
      developed world. We studied compliance to a secondary prevention programme for
      CHD patients and possible gender differences. DESIGN AND METHODS: Cross-sectional
      survey of CHD patients aged up to 75 years attending a hospital cardiology
      outpatient clinic (n = 441; 16 cardiologists) and 12 primary care centres (n =
      319; 28 primary care physicians), by means of a questionnaire. RESULTS:
      Therapeutic goals in hospital care and in primary care were reached by 36% and
      29% (P < 0.05) for cholesterol, 42% and 50% (P < 0.01) for triglycerides, 66% and
      72% for blood glucose, 84% and 86% for blood pressure, and 16% and 20% for
      smoking, respectively. Echocardiography was more frequent in hospital care
      patients (odds ratio 2.69, P < 0.001). ACE-inhibitors, beta-blockers,
      antiplatelet and anticoagulant therapy were prescribed similarly in both groups,
      antidiabetics were less common in hospital care (odds ratio 0.53, P < 0.05). Men
      were more often subject to echocardiography (odds ratio 2.59, P < 0.001). ACE
      inhibitors (odds ratio 2.04, P < 0.01), beta-blockers (odds ratio 1.82, P <
      0.001) and antiplatelet or anticoagulant drugs (odds ratio 1.82, P < 0.01) were
      more common in men; diuretics (odds ratio 0.49, P < 0.01) were more common in
      women. CONCLUSIONS: CHD patients have a high prevalence of modifiable risk
      factors. Few reach therapeutic goals for lipid levels, whereas other risk factors
      are better controlled. A secondary prevention programme is an important aid in
      preventing CHD but must be followed by further educational efforts in order to be
      more effective.

PMID- 11324374
TI  - Risk factors and coronary artery disease for asymptomatic women using electron
      beam computed tomography.
AB  - BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death for men
      and women in the United States. In 1995, 58,200,000 people were estimated to have
      the disease, claiming 960,592 lives, while 481,287 people died of coronary artery
      disease (CAD). Most people are unaware they have CAD, and death is often quite
      sudden. With more women surviving to old age, the absolute number of women dying
      from CVD exceeds that of men. METHODS: The study is cross-sectional. Electron
      beam computed tomography (EBCT) was employed to measure the amount of coronary
      artery calcium (CAC), a marker for CAD, in a population of patients referred to
      the Spokane Coronary Artery Center. A questionnaire was administered at the time
      of the patient's visit, when exposure to traditional risk factors was assessed.
      The effect of traditional risk factors on CAC was then determined. RESULTS: The
      effect of past smoking on CAC was evident, the effect of total cholesterol on CAC
      was moderate, while a history of hypertension appears to have an effect on the
      disease for older women. CONCLUSIONS: EBCT measurements of CAC can detect the
      effect of traditional risk factors on CAD and can be used to manage the disease
      in women.

PMID- 11324375
TI  - Epidemiology of cardiovascular risk factors among schoolchildren in Sousse,
      Tunisia.
AB  - BACKGROUND: In Tunisia, where the epidemiological transition phenomenon is well
      established, there are no data available at the population level on the
      cardiovascular disease (CVD) risk profile for children, although it is well known
      that risk factor development takes place in childhood. METHODS: We report an
      epidemiological survey based on a representative sample of 1569 urban
      schoolchildren of Sousse in Tunisia to assess the following CVD risk factors:
      hypertension, hypercholesterolaemia and other lipid disorders, obesity and
      tobacco consumption. RESULTS: The main results showed that girls had
      significantly higher levels of body mass index (BMI), diastolic blood pressure
      (DBP), total cholesterol, low-density lipoprotein (LDL) cholesterol and high
      density lipoprotein (HDL) cholesterol than boys, who however had significantly
      higher levels of systolic blood pressure (SBP). Total cholesterol was
      significantly correlated to BMI and decreased with age. Obesity (BMI = 27) was
      found in 7.9% of the study population and was significantly higher for girls
      (9.7%) than for boys (6%): chi 2 = 9.02, DF = 2, P = 0.011. Overweight (BMI = 25)
      was also significantly higher for girls (16%) than for boys (11.1%): chi 2 =
      8.21, DF = 1, P = 0.0041. Smoking habit concerned 7.6% of the study population;
      it was significantly higher for boys (14.7%) than for girls (1.1%): chi 2 =
      103.4, DF = 1, P < 0.00001. CONCLUSION: This study showed to some extent that
      Tunisia's urban population of schoolchildren is exposed early to CVD risk factors
      and all should be done to avoid the worsening of this profile. These results will
      serve as a baseline for assessment of future trends in the risk factors studied.

PMID- 11324376
TI  - Different cut-off points of decreased heart rate variability for different groups
      of cardiac patients.
AB  - BACKGROUND: Heart rate variability (HRV) differs by the type and stage of the
      disease, by age, by environment, and so on. Criteria for normal, moderately
      changed and pathologic values of HRV lack for routine clinical work with
      different groups of cardiac patients. METHODS: Twelve time and frequency domain
      HRV variables were analysed from 24-h Holter ECG monitoring in 2578 consecutive
      patients of both sexes (57% male) aged 15-91 (mean 54 +/- 13) years. Fifty-nine
      per cent of the patients were hospital out-patients, 15% came from the cardiac
      unit of an internal medicine department and 26% were undergoing stationary
      cardiac rehabilitation. Arrhythmias of aetiology other than coronary artery
      disease predominate in out-patients and coronary artery disease in in-patients.
      Limits of moderately and pathologically changed values were determined according
      to biostatistical principles. RESULTS: HRV differed by the age, sex and type of
      patients (MANOVA P < 0.001). Heart rate and all HRV measures decreased with age.
      Females had a higher heart rate but more pronounced vagally modulated activity
      than males. Out-patients had better HRV than in-patients. The cut-off level for a
      pathologic standard deviation of the normal R-R interval (a measure of overall
      HRV) ranged from 75 ms in female out-patients to 44 ms in male patients from the
      cardiac unit. Different cut-points for 12 HRV measures were obtained for 12 sub
      groups of patients. CONCLUSION: In view of the HRV differences between different
      cardiac patients, different limits of normal and decreased HRV are proposed for
      daily practice.

PMID- 11324377
TI  - [Disorientation in patients with organic brain disorders].
AB  - The aim of the study was to designate conditions in which disorientation appears
      in patients with organic brain disorders. This was made through analysis of
      relations between the disorientation and 10 variables describing the disorders.
      110 patients with various organic brain disorders was examined. In order to
      estimate the results of this investigation the method of cluster analysis
      (Wroclaw taksonomy) was used. Disorientation appeared to be in one cluster with
      the disorder of gestalting function in the Bender test, diagnosis, psychomotoric
      slowing, aphasia, type and localization of lesion and age of the patients. These
      features may be the conditions in which disorientation appears in the patients
      with organic brain disorders.

PMID- 11324378
TI  - [Orientation and simultaneous visuospatial synthesis in dementia and depression].
AB  - The presented paper discusses the orientation processes and simultaneous
      visuospatial synthesis ability in patients with dementia and depression. The
      disturbances of the orientation processes and the simultaneous visuospatial
      synthesis ability have proved characteristic of patients with dementia. The
      disorder of simultaneous visuospatial synthesis ability constituted one of the
      cognitive limits in patients with dementia. Patients with dementia aided
      themselves with long-term memory and the retrieval processes ability in the
      orientation processes. In patients with dementia simultaneous visuospatial
      synthesis ability, orientation processes, attention, short-term memory, retrieval
      processes decreased together with progression of the dementia processes. The
      simultaneous visuospatial synthesis ability in patients with depression was
      maintained at a high level. Memory and visuospatial learning and simultaneous
      visuospatial synthesis ability reflected aptly the level of the orientation
      processes in patients with depression. Only patients with depression helped
      themselves with the simultaneous visuospatial synthesis ability in the
      orientation processes. In ageing simultaneous visuospatial synthesis ability
      decreased together with age. Notional abstract thinking was related to the
      orientation processes and the simultaneous visuospatial synthesis ability only in
      those ageing.

PMID- 11324379
TI  - [Correlations between some features of social networks and treatment outcome in
      patients with schizophrenia three years after initial hospitalization].
AB  - There were studied correlations between some features of social networks of 56
      DSM-III schizophrenic patients and "specific aims of treatment": insight,
      satisfaction of the treatment, compliance, motivation for the treatment and
      "outcome of treatment" in psychopathological and social level three years from
      the first admission. There were used Fallow-up Chart, Bizon's Social Support
      Questionnaire, BPRS-LA scale and Social Assessment Scale (SAS). There were
      obtained statistically significant results concerning correlations between the
      type of support (concentrated, dispersed, and mixed) and the size of the extra
      familiar network and the "specific aims" of treatment. This means that patients
      who have a mixed type of social support and a extended extra-familiar social
      network obtain better specific treatment aims as: motivation for treatment, co
      operation in treatment, insight and a subjective satisfaction of treatment. There
      exists also significant correlation between some features of social network such
      as the range of network, the amount and localisation of support and the size of
      the extra-familiar network and the psychopathology level. The patients who get
      little support and those whose whole support is localised in family have higher
      level of negative symptoms measured with BPRS sub-scale. Patients of little range
      of the social network, including extra-familiar network show more positive
      symptoms three years after the first hospitalisation. There were found no
      correlations between the social network features and profession.

PMID- 11324380
TI  - [Relationship between structural brain abnormalities and psychopathologic profile
      in patients with schizophrenia].
AB  - Aim of this study was to determine the presence of structural brain
      abnormalities, dynamics of psychopathology three and seven years after the first
      hospitalisation and correlation between them. We examined 59 first admitted
      schizophrenic patients. We used computed tomography to examine structural brain
      abnormalities and BPRS-LA to measure the psychopathology level. CT and BPRS
      measures were both completed 3 years after the first admission. 7 years after the
      first admission the psychopathology level was measured with BPRS. We observed
      spaces in the brain and cortical sulci widened in 55 subjects (93%). The most
      commonly met structural brain pathology was a widening of the IIIrd ventricle and
      frontal cortex pathology. Assessment of the dynamics of psychopathology shows
      stability of the negative syndrome and increase of the positive syndrome and
      general psychopathology between the third and the seventh year of the illness.
      Three years after first admission, structural brain pathology in the left
      temporal cortex and frontal cortex correlate with the overall level of
      psychopathology measured with BPRS-LA, but this correlation vanishes in seventh
      year catch-up. Seven years after first admission subcortical cerebral pathology,
      especially in the subcortical frontal area correlate significantly (p < 0.01)
      with a lower level of positive symptoms.

PMID- 11324381
TI  - [Obsessive-compulsive disorders in adolescents with diagnosed schizophrenia].
AB  - The aim of the study was to assess the prevalence of OCD among 200 outpatients
      and inpatients (102 girls and 88 boys), 15-19 years old (mean age = 17.1 +/-
      0.29) with schizophrenia (DSM-III-R, DSM-IV) and to determinate the time of onset
      of OCD: at least 6 months before schizophrenic symptoms, together with
      schizophrenic symptoms, while treatment with neuroleptics (name of drug, doses,
      duration of pharmacotherapy). Patients were examined with SCID-P for DSM-III-R
      and DSM-IV, version for patient, Y-BOCS and a specially prepared questionnaire
      for determining the age of onset, duration of OCD and a clinical picture of OCD.
      OCD was diagnosed in 13% adolescent patients with schizophrenia. Primary OCD-
      before schizophrenic symptoms was noted in 2.0% of patients, OCD together with
      schizophrenic symptoms in 4.5% of subjects, and while pharmacotherapy with
      various atypical neuroleptics: clozapine, risperidone, olanzapine in 6.0% of
      young patients. The most of assessed patients received clozapine (35 subjects),
      24 subjects were treated with risperidone and 17 patients with olanzapine. It was
      determined that 14.3% of subjects used clozapine, 12.5% of subjects treated with
      risperidone and 5.9% treated with olanzapine presented OCD, where symptoms had
      appeared while in pharmacotherapy with these atypical neuroleptics. The
      differences were not statistically significant. OCD was not observed in these
      patients who had earlier treatment with classical neuroleptics (for example:
      haloperidol, perazine). It is possible that part of OCD in schizophrenic patients
      is induced by medication with new atypical neuroleptics, their influence on
      serotoninergic system, other, maybe the partial symptomatology of schizophrenia
      in a special subgroup of patients.

PMID- 11324382
TI  - [Subjective and objective evaluation of treating schizophrenia with classic or
      atypical drugs].
AB  - Subjective and objective evaluation of pharmacological treatment was made in 105
      schizophrenic in-patients. PANSS and Calgary scale as well as Van Putten scale
      were used. Fifty-four percent of subjects received classic neuroleptics and 46%-
      new atypical drugs for an average period of 8 weeks. The severity of
      schizophrenic symptoms during treatment as well as subjective evaluation of first
      effects of the drug did not differ among subjects treated with classic or
      atypical drugs. Depressive symptoms decreased significantly during treatment with
      atypicals but not with classic drugs. Also a significant decrease of depression
      was found under olanzapine treatment. The severity of neuroleptic-induced side
      effects did not differ in both groups. Neurological side effects were more
      prominent in subjects after 4 weeks of therapy with risperidone, in comparison to
      patients receiving olanzapine. Forty-seven per-cent of patients showed a
      dysphoric reaction to the first dose of medication. After treatment with atypical
      drugs, better subjective evaluation of pharmacotherapy correlated with less
      severe general and depressive schizophrenia symptoms. Patients' better evaluation
      of olanzapine treatment correlated with less severe schizophrenic general
      symptomatology. The subjective evaluation of treatment was better in patients
      with less severe neurological side-effects of atypical drugs (including
      olanzapine but not risperidone) and less severe autonomic side-effects of classic
      drugs. The evaluation of pharmacotherapy made by patients' family members did not
      correlate with subjects' opinions after distribution of the first dose of the
      drugs, but correlated significantly with patients' opinion after 8-weeks of
      treatment. The treatment received by the patients was judged better by the family
      members if less severe neurological side-effects were present.

PMID- 11324383
TI  - [Features of autism, autistic traits, autism: retrospective analysis of clinical
      symptoms in children treated in the Pediatric Psychiatric Clinic].
AB  - All currently accepted definitions of autism include three main criteria which
      have to be met for a diagnosis to be made. These are: disturbance of reciprocal
      social interaction, disturbance of communication and restriction of normal
      variation in behaviour and interests. The criteria used in the ICD-10 include all
      these domains. On the other hand, the number of mentally handicapping conditions
      and brain damage syndromes show the same triad of symptoms. Many of patients
      actually fulfill all currently accepted criteria for autism, but, for some reason
      do not receive the diagnosis. We analysed retrospectively the clinical picture of
      all children hospitalised in Department of Child Psychiatry in the last 10 years
      before the introduction of ICD-10 in Poland (1986-1996) and diagnosed as having
      autism, autistic traits or features. The group consist of 19 children (0.8% of
      all children hospitalised in that time). 4 of them had been diagnosed as having
      autism, 4 as having features of autism and 11 as having autistic traits.
      Additional diagnoses were: organic brain damage in 2 children, carnitine
      deficiency and cerebral palsy in 1 child and minimal brain dysfunction in 3
      cases. Despite of the diagnosis all children met current ICD-10 criteria for
      autism or atypical autism, according to age of onset. There were no significant
      differences in constellation of symptoms included in ICD-10 between groups
      divided according to the past diagnosis.

PMID- 11324384
TI  - [Genetic factors in the etiology of anorexia nervosa].
AB  - Anorexia nervosa (AN) is a disease of complex ethiopatogenesis. Population
      genetics studies suggest a significant role of genetic factors in the morbidity
      risk. Family and twin studies allow for the estimation of the heritability--the
      influence of genetic factors on the specific phenotype--of the anorexia nervosa
      in 50-80%. Due to the low prevalence of the disease, the adoption studies have
      not been performed. The rapid development of the molecular biology methods gives
      possibility for the searching of the specific genes increasing the risk of
      anorexia nervosa. Linkage studies are based on scanning the whole genome for loci
      associated with susceptibility to a certain disease. In the preliminary studies,
      no linkage was found between anorexia nervosa and the markers on the chromosomes
      1-5, 13 and X. In the association studies, relationship between vulnerability to
      AN and polymorphism in 5-HT2a receptor and uncoupling proteins gene were
      reported. These results need further confirmation.

PMID- 11324385
TI  - [Cardiovascular disorders in patients with anorexia nervosa].

PMID- 11324387
TI  - A kinder, gentler therapy?

PMID- 11324386
TI  - [Frequency and intensity of behavioral and psychological symptoms in the course
      of Alzheimer's disease].
AB  - The aim of the study was: 1) to estimate the occurrence and intensity of some
      psychopathological symptoms in the course of Alzheimer's disease, and 2) to
      examine whether the occurrence of behavioral and psychological symptoms increases
      with the deepening of dementia process among persons with Alzheimer's disease
      living in their homes with outpatient treatment. The study was conducted among 94
      persons (38 men and 56 women ageing from 52 to 86 years (x = 72.4 +/- 6.9), with
      education: from 2 to 17 years (x = 11.2 +/- 3.7). Three subgroups were selected
      for study with regard to the intensity of dementia process, estimated according
      to Clinical Dementia Rating (CDR): very mild (n = 16, x = 71.4 +/- 6.7), mild (n
      = 43, x = 72.6 +/- 7.9), moderate (n = 35, x = 72.5 +/- 6.9). Subjects in group
      II and III fulfill diagnostic criteria of dementia according to ICD-10, DSM IV
      and criteria of probable AD according to NINCDS-ADRDA. In the estimation of
      occurrence of behavioral and psychological disturbances: Alzheimer's Disease
      Assessment Scale--non-cognitive behavior (ADAS-non-cog) and subscale "Change in
      Personality, Interests, Drive" of Blessed Dementia Scale were used. The results
      have shown that with the progress of dementia process, the occurrence of the
      following psychopathological symptoms such as: hallucinations, intensive motor
      activity, purposeless hyperactivity, pacing, rigidity increases and there is a
      relinquishment of hobbies. In addition, regardless of the stage of dementia, such
      behaviors as: apathy, depression, tearfullness, impaired emotional control and
      disturbances of appetite were observed relatively frequently.

PMID- 11324388
TI  - Photo quiz. Disseminated superficial actinic porokeratosis.

PMID- 11324389
TI  - Papular acrodermatitis of childhood: the Gianotti-Crosti syndrome.
AB  - Papular acrodermatitis of childhood (PAC), also known as Gianotti-Crosti
      syndrome, is a self-limited disorder with acute onset generalized lymphadenopathy
      and monomorphic lentil-sized, dense, nonconfluent, symmetric, flat-topped, non
      pruritic papules. We describe 2 patients, one with anicteric hepatitis,
      lymphocytosis, and positive hepatitis B surface antigenemia, and the other with a
      cytomegalovirus (CMV) infection.

PMID- 11324390
TI  - What's eating you? Dermacentor variabilis.

PMID- 11324391
TI  - Eruptive xanthomas and chest pain in the absence of coronary artery disease.
AB  - Because hyperlipidemia may present as xanthomas, a dermatologist may be the first
      to diagnose these skin lesions and associated lipid abnormalities. Xanthomas are
      of concern because of their association with coronary artery disease and
      pancreatitis. We describe the case of a 40-year-old white male with chest pain
      and eruptive xanthomas. Laboratory tests revealed severe hypercholesterolemia,
      hypertriglyceridemia, and diabetes mellitus, and the histopathology of the skin
      lesions was consistent with eruptive xanthomas. Surprisingly, even with
      overwhelming risk factors for both atherosclerosis and pancreatitis, this patient
      did not show evidence of either disease process. After initiating therapy for the
      diabetes and hyperlipidemia, the patient has had no recurrence of chest pain, and
      the skin lesions have gradually resolved. The most likely explanation for this
      patient's pattern of symptoms and laboratory results is the chylomicronemia
      syndrome, which can be seen in patients with type I or type V
      hyperlipoproteinemia.

PMID- 11324392
TI  - Ibuprofen-induced bullous leukocytoclastic vasculitis.
AB  - A dramatic case of ibuprofen-induced bullous leukocytoclastic vasculitis (LCV) is
      described in a patient with a history of prior sensitization to ibuprofen, a
      common household nonsteroidal anti-inflammatory drug (NSAID) that has few
      reported adverse skin reactions. Bullous LCV is a relatively rare clinical
      presentation of LCV, which requires differentiation from other blistering
      diseases, including bullous erythema multiforme, bullous fixed drug eruption,
      linear IgA bullous dermatosis, and bullous pemphigoid. The distinctive
      histopathologic changes of leukocytoclastic vasculitis readily distinguish this
      bullous eruption from the others.

PMID- 11324393
TI  - Symmetrically distributed orange eruption on the ears: a case of lupus vulgaris.
AB  - Although the incidence and morbidity of tuberculosis (TB) have declined in the
      latter half of the last decade in the United States, the number of cases of TB
      (especially cutaneous TB) among those born outside of the United States has
      increased. This discrepancy can be explained, in part, by the fact that cutaneous
      TB can have a long latency period in those individuals with a high degree of
      immunity against the organism. In this report, we describe an individual from a
      region where there is a relatively high prevalence of tuberculosis who developed
      lupus vulgaris of the ears many years after arrival to the United States.

PMID- 11324394
TI  - Noonan syndrome: a case with recurrent keloid formation.
AB  - We describe a 6-year-old boy who presented with erythema and horny, follicular
      papules on the lateral aspects of the eyebrows and extensor surfaces of the arms.
      The condition was diagnosed as ulerythema ophryogenes and keratosis pilaris
      atrophicans faciei. The patient had the characteristic features of Noonan
      syndrome, including dysmorphic facial appearance, congenital heart disease,
      pectus excavatum, and cubitus valgus, accompanied by a tendency for keloid
      formation.

PMID- 11324395
TI  - Early stage onychomadesis presenting as painful swellings of proximal nail folds.
AB  - Two Korean men complained of painful erythematous swellings of the proximal nail
      folds. When we removed the overlying nail plates, we observed new ones growing
      under the old ones. These painful swellings disappeared after the affected nails
      were extracted. We found typical onychomadesis in another finger during the
      follow-up, suggesting that the initial condition marked the onset of
      onychomadesis. Because both patients had plaster casts removed recently and
      histories of trauma, it was hypothesized that trauma might be responsible for
      this peculiar condition.

PMID- 11324396
TI  - Kwashiorkor in patients with AIDS.
AB  - Kwashiorkor, a form of severe protein-energy malnutrition that entails loss of
      lean body weight, occurs endemically among children in many parts of the world
      but also has been documented in adults. We report a case of kwashiorkor in an HIV
      positive adult male. Cutaneous findings are striking, and skin, hair, and nails
      are affected. Although kwashiorkor occurs in patients with HIV-AIDS, the skin
      manifestations have not been emphasized in the dermatologic literature. Indeed,
      dermatologists may play a vital role in diagnosing this treatable condition.

PMID- 11324397
TI  - Fingertip dermatitis in a retail florist.
AB  - Prevalence of plant contact dermatitis in retail florists varies with exposure,
      and the number of reports of contact allergy to cut tulips is rather small. Alpha
      methylene-gamma-butyrolactone is better known as the cause of both Alstroemeria
      dermatitis in retail florists and tulip finger in wholesale floral workers who
      handle the bulbs. Our patient presented with prominent erythema, scaling, and
      peeling of the skin of the thumb, index, and middle fingers of his right hand.
      Results of a patch test to alpha-methylene-gamma-butyrolactone were strongly
      positive, and the patient determined that the exposure had occurred when he
      stripped leaves from the tulip stems to arrange cut flowers. Other natural
      sources of the antigen include Alstroemeria; Bomarea; Dioscorea hispida;
      Erythronium; Gagea; Fritillaria; and at least one species of onion, Allium
      triquetrum.

PMID- 11324398
TI  - Perianal pseudoverrucose papules and nodules mimicking condylomata acuminata and
      child sexual abuse.
AB  - We describe an 8-year-old male with perianal nodules and papules mistaken for
      condylomata acuminata by the referring physician, raising the question of sexual
      abuse. Examination and histology at the Department of Dermatology supported the
      diagnosis of perianal pseudoverrucose papules and nodules (PPPN).

PMID- 11324399
TI  - Who is caring for our children?

PMID- 11324400
TI  - The primacy of the primary dentition.

PMID- 11324401
TI  - Tooth-position, arch-size, and arch-shape in the primary dentition.
AB  - Tooth positions and dental arch forms are related to the growth of the cranio
      facial complex. To determine the positions of primary teeth and size and shape of
      the primary dental arches, sixty dental casts of young children (thirty boys and
      thirty girls) with normal occlusions were examined. In all casts the coordinates
      of cusp tips of primary canines and molars, and mesial and distal line angles of
      primary canines and incisors were digitized. The computer-generated curves were
      made for the maxillary and mandibular arches using a polynomial model. The
      results show that there were three major cusp-to-fossa and one cusp-to-marginal
      ridge relations in primary molar intercuspation. On average, girl's dental arches
      were smaller than boy's dental arches. The mean curves of mandibular arches in
      anterior segments were gentler than those of maxillary arches.

PMID- 11324402
TI  - Descriptive classification of variations in primary mandibular first molars.
AB  - Variability in tooth morphology can play a significant role in the achievable
      results of restorative treatment. This study identified the variations of
      morphology of the primary mandibular first molar (Type I and II coronal outline
      and Type A-F cusp alignment.) Type I coronal outline was found more frequently
      (86 percent) than Type II (14 percent). 93 percent of the primary mandibular
      first molars comprise four cusps, 5 percent comprise five cusps, and 2 percent
      comprise 3 cusps (F). Among the four-cusp group, 70 percent had an oblique
      transverse ridge (C), 25 percent had a poorly developed transverse ridge (A).
      Among the five-cusp-group, 67 percent had a distal cusp (E), and 33 percent had a
      fifth lingual cusp (D). The most frequent combination of coronal outline and cusp
      alignment was Type I-C (60 percent), and followed by Type I-B (22 percent), II-C
      (5 percent), and II-A (4 percent).

PMID- 11324403
TI  - Components of anterior crossbite in the primary dentition.
AB  - The craniofacial and dental components of anterior crossbite children with a full
      primary dentition were investigated by means of a cephalometric and correlation
      study. A group of thirty-two Taiwanese children with anterior crossbite was
      compared to a group of thirty-two normal occlusion subjects. The facial profile
      polygon method was used for assessing morphological characteristics of
      craniofacial pattern. According to the results, early signs of anterior crossbite
      are present in the primary dentition. A smaller anterior cranial base, a retruded
      positioning of the maxilla and a smaller interincisal angle were found in the
      anterior crossbite children. A correlation analysis between all the cephalometric
      measurements was carried out, and the significance of the differences between
      correlation coefficients of the two groups was calculated. the normal occlusion
      group shows negative correlation between interincisal angle and FH-SGn angle. The
      anterior crossbite group shows positive correlation between FH-NPog angle and U1
      FH angle.

PMID- 11324404
TI  - Relation of oral yeast infection in Brazilian infants and use of a pacifier.
AB  - The frequency of oral yeast ingestion and its relationship with sucking and
      feeding habits was described in children from one to 18 months of age. Yeasts
      were detected in 58.3 percent of children and the most prevalent species were
      Candida parapsilosis and Candida albicans. The use of a pacifier was positively
      associated with the frequency of yeast infection and with the levels of these
      microorganisms in the mouth. No relationship was detected between the prevalence
      of yeast and breast-feeding or bottle-feeding habits. The results suggest that
      use of a pacifier is an important local factor in the colonization and
      proliferation of yeast in the oral cavity.

PMID- 11324405
TI  - Fluoride content of infant formulas prepared with deionized, bottled mineral and
      fluoridated drinking water.
AB  - Usually infant milk formula is the major source of fluoride in infancy. Fluoride
      concentrations in ten samples of powdered milk formulas, prepared with deionized,
      bottled mineral, and fluoridated drinking water were determined after HMDS
      facilitated diffusion, using a fluoride ion specific electrode(Orion 9609).
      Fluoride concentrations ranged from 0.01 to 0.75 ppm; from 0.02 to 1.37 ppm and
      from 0.91 to 1.65 ppm for formulas prepared with deionized, bottled mineral (0.02
      to 0.69 ppm F) and fluorinated drinking water (0.9 ppm F), respectively. Possible
      fluoride ingestion per Kg body mass ws estimated. With deionized water, only the
      soy-based- formulas should provide a daily fluoride intake of above the suggested
      threshold for fluorosis. With water containing 0.9 ppm F, however, all of them
      would provide it. Hence, to limit fluoride intakes to amounts <0.1 mg/kg/day, it
      is necessary to avoid use fo fluoridated water (around 1 ppm) to dilute powdered
      infant formulas.

PMID- 11324406
TI  - Use of fluoridated dentifrice and glucose retention at the approximal areas of
      anterior teeth.
AB  - The present study was undertaken to learn to what extent the use of dentifrice
      with fluoride affected glucose retention after glucose rinsing. Fifty-eight
      subjects consisting of forty male adults and eighteen female adults whose average
      age was 21.9 years were divided at random into two groups; one group used
      fluoridated dentifrice and the other group used nonfluoridated dentifrice.
      Subjects rinsed their mouths for fifteen seconds with 20 mL of 0.5 M glucose
      solution. Samples of saliva were taken from the approximal areas between the
      right and left central incisors of the maxilla and mandible by inserting the tip
      portion of a paper point three-minutes after the glucose rinsing, sample of
      saliva were taken from the neighboring approximal areas of the left central and
      left lateral incisors. Glucose content of the paper points was determined using
      the enzyme membrane method. Determinations were made before and at the end of the
      first, third, and fifth month over a five-month period. Fluoride concentrations
      in the resting saliva were also determined in different months during this
      period. At three-minutes and six-minutes, glucose retention in the group using
      fluoridated dentifrice was found to decrease slightly throughout the experiment;
      while glucose retention in the group on nonfluoridated dentifrice leveled off or
      increased in the fifth month. Fluoride concentration in the resting saliva
      increased during the experiment in the group using fluoridated dentifrice; while
      fluoride concentration in the group using nonfluoridated dentifrice did not
      change. It was concluded that the regular use of fluoridated dentifrice made
      glucose retention slightly lower and fluoride level in whole saliva higher.

PMID- 11324407
TI  - Nursing-bottle syndrome caused by prolonged drinking from vessels with bill
      shaped extensions.
AB  - Our investigating 186 infants between the ages of one and six with carious
      destruction of the maxillary primary incisors, it was learned which risk factors
      were responsible for the condition known as nursing bottle syndrome. One hundred
      and twenty-eight infants (68.8 percent) were given a nursing bottle, twelve (6.5
      percent) a feeding cup or other bottles with bill- shaped extensions, and forty
      one (22.0 percent) both a nursing bottle and vessels with bill-shaped extensions;
      in all cases the feeding was excessive and prolonged beyond the first year of
      life. An additional five infants (2.7 percent) were breast-fed excessively beyond
      the first year. The results confirm the risk of tooth destruction, typical of
      nursing bottle syndrome, by prolonged and frequent consumption of cariogenic
      beverages from vessels with bill-shaped extensions. It is important, therefore,
      that a warning regarding dental health hazards of such feeding methods be issued.

PMID- 11324408
TI  - Parental beliefs on the origins of child dental fear in The Netherlands.
AB  - The aim of this study was to assess parental beliefs on the causes and prevention
      of child dental fear in the Netherlands. The parents of 123 children (67 high
      fearful and 56 low fearful children) were interviewed about the causes of their
      children's dental fears, and about factors contributing to the prevention of this
      fear. Parents attributed their child's dental fear to the following factors:
      invasive dental experiences (37 percent), medical problems (19 percent), child's
      temperament (16 percent), negative dentist behavior (13 percent) and social
      influences (5 percent). In the prevention of child dental fear, an empathetic
      dentist (34 percent) and parental guidance (30 percent) were mentioned most
      frequently. In conclusion, conditioning factors were reported to be highly
      important in the development of child dental fear. Some of the parents, however,
      indicated temperamental factors to have played a role, suggesting that subgroups
      of dentally fearful children exist. These temperamental or psychological factors
      seem also to contribute substantially to the development of dental fear. Possible
      differences in parental attributional style are discussed.

PMID- 11324409
TI  - 1,304,594 births to unmarried women in 1999.
AB  - The National Center for Health Statistics reported that out-of-wedlock child
      bearing has leveled off or slowed down in 1999. But in almost every single year
      between 1940 and 1999 the number of births to unmarried women increased. In 1999,
      more than 1.3 million children were born to unmarried women. A review is provided
      of these developments through the end of the 1990s, together with 1) the
      economics of single parenthood,2) the reality that increasing numbers of these
      new mothers ar in the general workforce and 3) the added impact of youngsters
      with mental retardation and other disabilities on single parent families.

PMID- 11324410
TI  - An inverted supernumerary tooth: report of case.
AB  - A nine-year old male child presented in the Department of Pedodontics with the
      chief complaint of pain and swelling int the mid-palatal region during
      mastication. Clinical examination revealed a hard swelling in the palate.
      Radiographic examination disclosed the presence of an inverted "mesiodens like"
      supernumerary tooth. Surgical extraction was planned.

PMID- 11324411
TI  - Simultaneous presence of a congenitally missing premolar and supernumerary
      incisor in the same jaw: report of case.
AB  - Supernumerary teeth and hypodontia can be regarded as opposite developmental
      phenomena. An eight-year-old girl presented a concomitant occurrence of a
      supernumerary tooth and two congenitally missing teeth. The supernumerary tooth
      was found in the left maxillary incisor region, while the left second premolar in
      the maxilla and the left lateral incisor in the mandible were congenitally
      missing. The supernumerary tooth showed a similar color and morphology to those
      of the maxilla lateral incisor, and the lateral incisor on the mesial side was
      diagnosed as a supernumerary tooth from dental age, eruption time, and
      mesiodistal crown dimension. The supernumerary incisor was guided labially to
      cure an anterior cross-bite, and the lateral incisor, canine, and first premolar
      were guided distally to compensate for the space left by the congenitally missing
      left second premolar.

PMID- 11324412
TI  - Unusual impaction of inverted primary incisor: report of case.
AB  - A tooth that fails to erupt into a normal functional position by the time it
      normally should is considered impacted. Impactions of primary teeth are extremely
      rare, but when it does occur it usually involves the first and second molar. The
      purpose of this article is to present a case of a four-year-old patient with an
      impaction of an inverted primary mandibular incisor. On the basis of the
      patient's family history, the case might be considered as microform of ectodermal
      dysplasia.

PMID- 11324413
TI  - Signs of medullar aplasia in the oral cavity: report of case.
AB  - Medullar aplasia is a hematological disease characterized by medullar dysfunction
      that results in a marked decrease of various hematological cellular elements.
      This produces anemia, infections of different etiologies and also, spontaneous or
      provoked hemorrhagic syndromes of varying importance. A case of medullar aplasia
      affecting a child, diagnosed after a tooth extraction is reported, and
      accompanied by its pathological characteristics. In addition, an easy reading
      E.L.I.S.A/ test for diagnosing herpes virus type 1 or 2 is presented.

PMID- 11324414
TI  - Individual and ethnic differences in CYP2C19 activity in Chinese populations.

PMID- 11324415
TI  - Effects of 2-[3-estrone-N-ethyl-piperazine-methyl]tetracycline (XW630) on
      osteoporosis in ovariectomized rats.
AB  - AIM: To study the effects of 2-[3-estrone-N-ethyl-piperazine-methyl]tetracycline
      (XW630) on experimental osteoporosis in ovariectomized (OVX) rats. METHODS: Serum
      estradiol (E2) content and bone 1-carboxyglutamic acid-containing protein (BGP)
      content were measured by radioimmunoassay. With undecalcified bone section and
      tetracycline intraperitoneal labeling, the bone static and dynamic data were
      studied in right femur samples. RESULTS: After treatment with XW630 2.5 mg.kg-1,
      serum BGP content increased by 75.7% but there was no change in serum E2 content
      and uterus weight compared with OVX rats. Compared with OVX rats, the static data
      of trabecular bone volume/total tissue volume, trabecular bone volume/sponge bone
      volume, and mean trabecular plate density were enhanced after treatment with
      XW630 for 13 wk. The dynamic data of single-labeled surface, double-labeled
      surface, trabecular osteoid surface, and bone formation rate in tissue level in
      XW630 group were increased and osteoid maturation period was shortened.
      CONCLUSION: XW630 enhanced bone activation frequency and increased trabecular
      connectivity, stability, and strength. XW630 stimulated bone formation and
      inhibited bone resorption with no effect on reproductive system.

PMID- 11324416
TI  - Atypical antipsychotic effects of quetiapine fumarate in animal models.
AB  - AIM: To evaluate the effect of quetiapine fumarate in animal models of
      schizophrenia and its possibility to induce extrapyramidal side effects (EPSE).
      METHODS: The enhancement of immobility in a forced swimming test of mice induced
      by repeated treatment with phencyclidine and amphetamine swimming "normalization"
      test of mice were used as animal models of negative and positive symptoms of
      schizophrenia, respectively. The paw test of rats was used to evaluate the
      possibility by quetiapine fumarate to induce EPSE. RESULTS: After treatment with
      phencyclidine (10 mg.kg-1.d-1, s.c., 14 d), the immobility time in the forced
      swimming test of mice was increased (P < 0.01). Quetiapine fumarate (20, 40, and
      80 mg.kg-1, ig) and clozapine (10 and 30 mg.kg-1, ig) attenuated the enhanced
      immobility in the forced swimming test induced by repeated treatment with
      phencyclidine (P < 0.01), whereas haloperidol (0.3 and 1 mg.kg-1, ig) had no
      effect. In amphetamine swimming "normalization" test, quetiapine fumarate
      ameliorated the disorder induced by amphetamine in a dose-dependent manner. In
      paw test, quetiapine fumarate was much less effective in increasing the forelimb
      retraction time (FRT) than the hindlimb retraction time (HRT). The minimal
      effective dose (MED) of HRT (MEDHRT) and FRT (MEDFRT) of quetiapine fumarate was
      20 mg.kg-1 and 100 mg.kg-1, respectively, and the ratio of MEDFRT to MEDHRT was
      5. CONCLUSION: The effects of quetiapine fumarate in these models indicated its
      clinical effect on schizophrenia with a reduced liability to produce EPSE.

PMID- 11324417
TI  - Antisense oligodeoxynucleotide inhibits vascular endothelial growth factor in
      human glioma cells.
AB  - AIM: To study the effects of antisense vascular endothelial growth factor (VEGF)
      oligodeoxynucleotide (ODN) on the expression of VEGF in human glioma cell line
      (A172 cells). METHODS: VEGF mRNA level was measured by semiquantification reverse
      transcriptase polymerase chain reaction (RTPCR). VEGF protein expression in the
      cells was determined by immunohistochemistry. VEGF protein level in the media was
      measured by ELISA. RESULTS: When the cells were treated with antisense VEGF ODN
      (6.25-50 mumol.L-1), VEGF mRNA level in the cells decreased remarkably in a
      concentration-dependent manner. No change was found when the cells were treated
      with sense or missense ODN. When the cells were treated with antisense VEGF ODN
      25 mumol.L-1, VEGF protein level decreased greatly both in the cells and the
      media. CONCLUSIONS: Antisense VEGF ODN inhibited VEGF expression specifically in
      A172 cells in vitro and thus the results provided the basis for the further
      studies in vivo.

PMID- 11324418
TI  - Volume- and calcium-activated chloride channels in human umbilical vein
      endothelial cells.
AB  - AIM: To characterize the properties of chloride currents and its modulation in
      human umbilical vein endothelial cells (HUVEC). METHODS: Using whole-cell patch
      clamp recording techniques. RESULTS: Exposure of HUVEC to 13.5% and 27% hypotonic
      solution (HTS) induced a current ICl, vol. This current was correlated with the
      changes in cell volume and showed a modest outward rectification. It was slowly
      inactivated at positive potential (> 50 mV), and it was time- and voltage
      independent in kinetics. The current densities (pA/pF) were 20 +/- 3 (13.5% HTS)
      and 58 +/- 4 (27% HTS, n = 7), respectively at +100 mV test potential. Applying
      GTP gamma s (300 mumol.L-1) elicited a current similar to ICl, vol, while cAMP
      (0.5 mmol.L-1) had no effect on the current. Increase in [Ca2+]i, either by
      directly loading cells with high concentration of Ca2+ (CaCl2), or by perfusing
      vasoactive agonist ATP (10 mumol.L-1), activated ICl, Ca. The current density was
      only (23 +/- 5) pA/pF (n = 8 cells). Such current was slowly activated at
      positive potential, inactivated quickly at negative potential, and showed strong
      outward rectification. Both currents were inhibited by DIDS and verapamil.
      Challenging a cell with elevated [Ca2+]i and HTS activated ICl, vol on the top of
      ICl, Ca in the same cell, suggested co-existence of these two currents and that
      they were modulated by different ways. cAMP-regulated chloride channel and ClC
      (chloride channel family) channel were absent. CONCLUSION: HUVEC express two
      kinds of chloride channels, ICl, vol activated by change in cell volume and ICl,
      Ca by elevation of [Ca2+]i, respectively.

PMID- 11324419
TI  - Biphasic manner of melittin on isolated guinea pig atria.
AB  - AIM: To investigate the effect of melittin (Mel) on isolated guinea pig atria.
      METHODS: The effect of Mel on the contraction and heart rate of isolated guinea
      pig atria at different concentrations was determined. RESULTS: Mel at a lower
      concentration (0.1-0.8 mumol.L-1) enhanced the contraction of left atria in a
      concentration-dependent manner; but at a higher concentration (1.6-12.8 mumol.L
      1) it exerted an inhibitory effect. At 0.1-30 mumol.L-1 it was found to increase
      heart rate of right atria. In addition, verapamil (Ver) 0.3 mumol.L-1 was found
      to depress the effect of Mel. CONCLUSION: Mel possesses a biphasic effect on left
      atria and a positive chronotropic effect on right atria. Its mechanism might be
      related with Ca2+ channel.

PMID- 11324421
TI  - Antisense Ca(2+)-calmodulin dependent protein kinase oligonucleotide inhibits
      bFGF-induced proliferation of rat vascular smooth muscle cells.
AB  - AIM: To investigate the role of Ca(2+)-calmodulin dependent protein kinase
      (CCDPK) on basic fibroblast growth factor (bFGF)-induced vascular smooth muscle
      cell (VSMC) proliferation and the inhibitory effect of antisense CCDPK
      oligonucleotides (ODN). METHODS: Before being exposed to bFGF, cultured rat VSMC
      CCDPK activity was inhibited by pretreatment with either a phosphorothioate
      protected 17-mer antisense CCDPK ODN-directed against the initiation of
      translation sites of the p42 and p44 CCDPK isoform or with CCDPK kinase inhibitor
      PD98059. All ODN were introduced into cells by liposomal transfection. DNA
      synthesis was measured by [3H]thymidine incorporation. P44- and p42-CCDPK protein
      expression and phosphorylation were measured by Western blot. RESULTS: PD98059
      inhibited bFGF-induced phosphorylation of CCDPK and DNA synthesis. Antisense
      CCDPK ODN 0.2-0.8 mumol.L-1 reduced both p44- and p42-CCDPK expression and
      phosphorylation of CCDPK in a concentration-dependent manner and DNA synthesis
      induced by bFGF. Lipofectin alone or sense and random CCDPK ODN did not affect
      p44- and p42-CCDPK protein expression or bFGF-induced phosphorylation of CCDPK or
      DNA synthesis. CONCLUSION: bFGF-stimulated rat VSMC proliferation is mediated by
      CCDPK. The antisense CCDPK ODN can inhibit bFGF-induced VSMC proliferation
      through down-regulating p44- and p42-CCDPK level.

PMID- 11324420
TI  - Apoptosis induced by ceramide in hepatocellular carcinoma Bel7402 cells.
AB  - AIM: To study the biological function of ceramide signaling in Bel7402 cells.
      METHODS: Inhibition of cell growth was assayed using MTT method. Morphologic
      assessment of apoptosis was performed with fluorescence microscope. DNA
      fragmentation was detected by electrophoresis and flow cytometry. The levels of
      protein p53, Bcl-2, and Bax were measured with Western blot. RESULTS: Bel7402
      cells treated with C2-ceramide underwent cell proliferation inhibition. IC50
      value was 14.28 mumol.L-1. After treatment of Bel7402 with ceramide, the
      morphologic changes including reduction in volume, nuclear chromatin
      condensation, fluorescence strength were observed. SubG1 peaks were detected on
      flow cytometry (FCM). Agarose gel electrophoresis of DNA from cells treated with
      ceramide revealed "ladder" pattern. The Western blot assay from cell extracts
      showed that the levels of protein p53 were decreased after ceramide treatment.
      The levels of protein Bcl-2 were decreased also. But the levels of Bax protein
      showed no difference between untreated cells and treated cells. CONCLUSION:
      Ceramide induces apoptosis in Bel7402 cells, related to Bcl-2 down-regulation.

PMID- 11324422
TI  - Effects of dihydroartemisinin on fine structure of erythrocytic stages of
      Plasmodium berghei ANKA strain.
AB  - AIM: The fine structural changes of Plasmodium berghei ANKA strain after
      treatment with the dihydroartemisinin (DATM) were observed. METHODS: DATM 180
      mg.kg-1.d-1 was given ig to outbreed NIH mice infected with P. berghei ANKA
      strain. Blood samples were collected, embedded and examined by electron
      microscopy. RESULTS: In P. berghei ANKA strain, 1 h after drug administration,
      the parasites food vacuole membranes were destroyed, and the pigment grains
      showed some changes. The nucleus membrane, cytomembrane, and food vacuole
      membranes were stratified 2 h after administration. At the same time, swelling
      and separation of the outer and inner membrane or shrinking of the mitochondria
      were seen. Stripped nuclear and cytoplasm membrane were developed and
      vacuolizations were seen 4 h later. Eight hours after administration, a large
      number of parasite structures were destroyed except for a few parasite autophagic
      vacuoles. CONCLUSION: DATM was a fast-acting and effective antimalarial drug. Its
      primary target is the membrane system. No obvious resistant characteristics were
      found upto 24 generations after resistant induction test for 4 months.

PMID- 11324423
TI  - Antidiabetic effect of Oenanthe javanica flavone.
AB  - AIM: To study the antidiabetic effect of Oenanthe javanica flavone (OjF).
      METHODS: Mice were injected i.v. with alloxan 90 mg.kg-1 to induce diabetes.
      Blood glucose, serum lipid, and pancreatic amylase were determined with Automatic
      Biochemistry Analysor. Serum insulin was determined by radioimmunoassay. The
      pancreas and islets were examined under microscope. RESULTS: OjF 200 mg.kg-1
      reduced the blood glucose in normal mice from 0.5 to 6 h after a single
      administration ig. OjF 200 and 400 mg.kg-1 ig daily for 10 d decreased the blood
      glucose in alloxan-induced hyperglycemic mice (P < 0.05, P < 0.01). OjF promoted
      the release of insulin both in normal and in diabetic mice. OjF decreased serum
      triglyceride and raised the lowered pancreatic amylases in diabetic mice (P <
      0.01, P < 0.01). The islet-injured changes of OjF-treated group were similar to
      those of control in histology examination, but to a lesser degree. CONCLUSION:
      OjF possessed the hypoglycemic and hypotriglyceride actions, mainly concerned
      with promoting release of insulin from B-cells in islets of langerhans.

PMID- 11324424
TI  - Molecular mechanism of apoptosis induced by ricin in HeLa cells.
AB  - AIM: To study the morphological changes and molecular mechanism of HeLa cell
      apoptosis induced by ricin. METHODS: HeLa cells were coincubated with ricin 0.05
      mumol.L-1 for 1, 2, 3, 6, 12, 18, and 24 h, then scanning electron microscopy
      (SEM), transmission electron microscopy (TEM), Western blot cell cycle, cell
      cytotoxicity, and cell viability were assayed. RESULTS: The typical apoptosis was
      induced by ricin 0.05 mumol.L-1 and necrotic cells increased after being cultured
      with ricin 0.05 mumol.L-1 for more than 12 h. The apoptotic cells mainly showed
      cytoplasmic membrane blebbing, chromatin condensation and fragmentation, and
      crescentic nuclear and membrane bound apoptotic bodies formation. No detectable
      levels of p53, Bax, Bcl-2 and the subunit p20 of interleukin-1 beta-converting
      enzyme (ICE) were found by Western blot, but the active subunit p17 of 32-kDa
      putative cysteine protease (CPP32) was detected at 3, 6, and 9 h after ricin
      treatment. The activity of CPP32 in HeLa cells increased 4 to 5 folds after being
      treated with ricin 0.05 mumol.L-1 and reached the peak at 6 h of treatment. There
      was no significant difference of ICE activity between the ricin treated cells and
      control cells. The percentage of G2/M cells increased from 13.9% +/- 0.5% to
      33.2% +/- 0.5% after 24 h of ricin 0.05 mumol.L-1 treatment. CONCLUSION: CPP32
      but not ICE was involved in the ricin-induced apoptosis in HeLa cells. Ricin 0.05
      mumol.L-1 had no effect on the G0/G1 phase of cell cycle, but induced G2/M
      arrest.

PMID- 11324425
TI  - Class III anti-arrhythmia drug E-4031 potentiates Na+/Ca2+ exchange current in
      rat ventricular myocytes.
AB  - AIM: To study the effects of E-4031 on the Na+/Ca2+ exchange currents (INa/Ca).
      METHODS: The quasi-steady state current-voltage relationship from the isolated
      rat ventricular myocytes was measured using whole-cell voltage-clamp techniques
      with a ramp pulse protocol. RESULTS: At potential of  mV, E-4031 5, 10, and 20
      mumol.L-1 increased Ni(2+)-sensitive current from (0.48 +/- 0.12), to (0.78 +/-
      0.20), (0.96 +/- 0.16), and (1.15 +/- 0.13) pA/pF, respectively;
      tetradecanoylphorbol acetate (TPA) 50 nmol.L-1 increased Ni(2+)-sensitive current
      from (0.60 +/- 0.16) to (1.33 +/- 0.25) pA/pF. Tamoxifen 20 mumol.L-1 completely
      prevented the current changes induced by E-4031 and TPA. CONCLUSION: E-4031
      stimulates the Na+/Ca2+ exchange via a protein kinase C-dependent pathway.

PMID- 11324426
TI  - Effect of six flavonoids on proliferation of hepatic stellate cells in vitro.
AB  - AIM: To study the effects of six flavonoids (fisetin, quercetin, apigenin,
      phloretin, hesperetin, and chalcone) on proliferation of hepatic stellate cell
      (HSC-T6 cells). METHODS: Cell proliferation was measured by crystal violet
      staining assay. RESULTS: Fisetin, quercetin, apigenin, phloretin, hesperetin,
      chalcone (6.25-50 mumol.L-1) inhibited the proliferation of HSC-T6 cells
      stimulated by serum, macrophage conditioned medium (MCM) and platelet-derived
      growth factor (PDGF) in a concentration-dependent manner. In the MCM-stimulated
      proliferation experiment, their IC50 were 21.48, 18.52, 19.75, 22.32, 30.32, and
      30.85 mumol.L-1, respectively. In the PDGF-stimulated proliferation experiment,
      their IC50 were 9.47, 9.48, 9.25, 12.25, 25.22, and 30.40 mumol.L-1,
      respectively. CONCLUSION: The six flavonoids inhibited the proliferation of
      hepatic stellate cells.

PMID- 11324427
TI  - Panax notoginseng saponins attenuated cisplatin-induced nephrotoxicity.
AB  - AIM: To study protective effects of Panax notoginseng saponins (PnS) against
      cisplatin-nephrotoxicity. METHODS: Cisplatin-induced nephrotoxicity in mice in
      vivo, and primary culture of rabbit proximal tubular cells (PTC) in vitro were
      established. Blood urea nitrogen, serum creatinine, cell viability, DNA
      interstrand cross-link, DNA-protein cross-link, and cytosolic free [Ca2+]i were
      assayed with diacetyl monoxime, alkaline picrate, trypan blue, ethidium bromide
      binding, 125I-postlabelling, and Fur 2-AM, respectively. RESULTS: With
      pretreatment for 2 d in mice, PnS 100 and 200 mg.kg-1.d-1 suppressed cisplatin
      induced high blood urea nitrogen level to 83% and 31%, and serum creatinine level
      to 86% and 42%, respectively (P < 0.01). Preincubated with PTC for 24 h, PnS 10
      and 100 mg.L-1 inhibited cisplatin-induced decrease of cell viability from 78% to
      81% (P < 0.05) and 89% (P < 0.01), respectively. PnS 10 and 100 mg.L-1 suppressed
      formations of DNA interstrand cross-link to 47% and 40%, DNA-protein interstrand
      cross-link to 77% and 42%, and cytosolic free [Ca2+]i overload in PTC to 70% and
      63%, respectively. (P < 0.01). CONCLUSION: PnS was a prophylactic for cisplatin
      induced nephrotoxicity, and mechanisms were relevant to the effects that PnS
      reduced cisplatin-induced cytosolic free [Ca2+]i overload, and formations of DNA
      interstrand cross-link and DNA-protein cross-link.

PMID- 11324428
TI  - Effects of XW630 on cell proliferation, iNOS activity, and cGMP content in human
      osteoblast-like cell line TE85.
AB  - AIM: To study the effects of 2-[3-estrone-N-ethyl-piperazine-methyl] tetracycline
      (XW630) in human osteoblast-like cell line TE85. METHODS: [3H]Thymidine
      incorporation and cell count for cell proliferation, radioimmunoassay for cyclic
      GMP (cGMP) content, and monitoring the conversion of [3H]arginine for inducible
      nitric-oxide synthase (iNOS) activity assay. RESULTS: After treatment with XW630
      for 48 h, [3H]thymidine incorporation and cell numbers increased by 62.7% and
      96.9%, respectively. NG-monomethyl-L-arginine (L-NMMA, an NOS inhibitor) induced
      a concentration-dependent inhibitory effect on the proliferation after treatment
      for 48 h. The inhibitory effect was prevented partially by XW630 (1.0 nmol.L-1).
      After treatment with XW630 for 12-48 h, iNOS activity and cGMP concentration
      increased in time-dependent manners. CONCLUSION: XW630 stimulated cell
      proliferation, enhanced iNOS activity and cGMP content in human osteoblast-like
      cell line TE85.

PMID- 11324429
TI  - Nonhistone protein purified from porcine kidney acts as a suicide substrate
      inhibitor on furin-like enzyme.
AB  - AIM: To search and purify a naturally occurring protein inhibitor of the furin
      like enzyme from the porcine kidney. METHODS: Recombinant kexin, a furin-like
      enzyme, from the yeast secretion expression was used as a target enzyme. The
      inhibitor component was extracted and purified from the acetone powder of porcine
      kidney. The inhibitory activity was monitored using a fluorogenic peptide
      substrate Boc-Arg-Val-Arg-MCA at spectrofluorimeter. RESULTS: The purified
      inhibitor component is a basic protein with an isoelectric point over 9.5. Its
      partial N-terminal sequence of 22 residues was determined, showing a high
      homology with nonhistone chromosomal protein HMG-17 in which there are four sites
      composed of dibasic residues, susceptible to be cleaved by the furin-like enzyme.
      This nonhistone protein could strongly compete with the fluorogenic substrate.
      However, this nonhistone protein would be degraded as a substrate by kexin if it
      was incubated with the enzyme for long time before adding the fluorogenic
      substrate, and subsequently lost its temporary inhibitory activity. CONCLUSION:
      The nonhistone protein isolated from the porcine kidney functioned as a suicide
      substrate inhibitor for the furin-like enzyme.

PMID- 11324430
TI  - Urethane-induced hyperglycemia.
AB  - AIM: To study the effects of urethane, at anesthetic dose, on the blood glucose
      levels in normal rats and hyperglycemic rats, and its effects on the hypoglycemic
      action of exogenous insulin in alloxan-treated rats. METHODS: Blood glucose
      concentration was measured with the glucose oxidase method. RESULTS: Urethane at
      anesthetic dose 1.5 g.kg-1 increased the blood glucose levels in fasting (to 2.6
      +/- 0.3 g.L-1, P < 0.01) or glucose-loaded (to 3.9 +/- 0.4 g.L-1, P < 0.01) rats.
      It did not modify the hyperglycemia induced by epinephrine (normal islet beta
      cells) or alloxan (impaired islet beta-cells). In the rats treated with alloxan,
      blood glucose level decreased to 1.8 +/- 0.7 g.L-1 at 200 min after
      administration of insulin from control level of 7.0 +/- 2.3 g.L-1, but the
      hypoglycemic action of exogenous insulin was abolished by urethane. CONCLUSION:
      Hyperglycemic action of urethane was due to its inhibiting effect on the
      hypoglycemic effect of insulin, except for its known mechanism of increased
      sympathetic release.

PMID- 11324431
TI  - Clearance of increased serum advanced glycosylation end products in patients with
      end stage renal disease by hemodialysis.
AB  - AIM: To study the effect of removal of hemodialysis using acetate membrane on
      serum advanced glycosylation end products (AGEP) in 36 patients (59.1 +/- 1.6)
      with end stage renal disease (ESRD). METHODS: Serum AGEP levels were determined
      with quantitative fluorescence spectrometry, flow injection analysis (FIA), and
      competitive enzyme-linked immunosorbent assay (ELISA) using a polyclonal antibody
      directed against AGEP. RESULTS: The serum AGEP levels in patients with ESRD
      quantified by fluorescence spectrometry, FIA, and ELISA were higher than those in
      controls [(25 +/- 5) vs (7.5 +/- 1.5), (6.1 +/- 1.8) vs (1.4 +/- 0.5), and (37 +/
      20) vs (9 +/- 10) kU/L, respectively] and markedly reduced to [(22 +/- 6), (4.2
      +/- 1.4), and (19 +/- 14) kU/L, respectively] after hemodialysis. CONCLUSION:
      Increased serum AGEP levels in the circulation of patients with ESRD were reduced
      effectively by hemodialysis.

PMID- 11324432
TI  - Effect of forskolin on acetylcholine-induced current in rat pheochromocytoma
      cells.
AB  - AIM: To study the effect of forskolin on the nicotinic receptor (NicR) of PC12
      cells. METHODS: The acetylcholine (ACh)-induced current (IACh) was measured on
      PC12 cells by whole-cell clamp technique. RESULTS: The IACh could be blocked by d
      tubocurarine chloride and atropine had no effect on IACh. Infusion of forskolin
      (1-50 mumol.L-1) caused an inhibition on IACh, which was reversible,
      concentration-dependent, and voltage-independent. Preincubation with 8-bromo
      adenosine-3', 5'-adenosine monophosphate (8-Br-cAMP), a cell-permeable cAMP
      analog which preferentially activated cyclic AMP-dependent protein kinase
      (CADPK), for 20 min, did not affect the IACh and the inhibitory effect of
      forskolin. Infusion of 1,9-dideoxyforskolin, an analog of forskolin which did not
      activate adenyl cyclase, also caused an inhibition on IACh. CONCLUSION: The
      inhibitory effect of forskolin on IACh in PC12 cells is not mediated by
      activating the adenyl cyclase. Probably, the lipophilic forskolin acts via
      perturbing the plasma membrane lipid structure and altering the function of the
      NicR.

PMID- 11324433
TI  - Potential mechanisms for cardiovascular protective effect of ethanol.
AB  - Epidemiological studies demonstrate a significant protective effect of moderate
      alcohol consumption on the incidence of cardiovascular diseases which accounts
      for the majority of deaths in the Western world. In this review, possible
      mechanisms to explain the cardioprotective effect of ethanol are discussed. While
      the prevailing theory supported by a number of clinical and animal studies
      indicates that the ability of ethanol to elevate serum high-density lipoprotein
      (HDL) cholesterol levels is an important mechanism in ameliorating cardiovascular
      disease, other mechanisms whereby ethanol could exert its beneficial effect have
      been proposed. Namely, its ability to affect platelet function and endothelial
      cell and vascular smooth muscle cell function (In this review, the terms alcohol
      and ethanol are used interchangeably).

PMID- 11324434
TI  - Colorectal cancer and non-steroidal anti-inflammatory drugs.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) can prevent or reduce the
      occurrence of colorectal cancers. Anti-carcinogenic properties of NSAIDs have
      been demonstrated in epidemiological studies of humans and experimental animals.
      In addition, clinical studies of familial adenomatous polyposis and sporadic
      adenomas have demonstrated that NSAIDs induce regression of colorectal adenomas
      and prevent formation of these tumors. NSAIDs thus induce early disruption of the
      adenoma-carcinoma sequence and may mainly suppress subsequent cancer formation at
      adenoma stage. The mechanism of the anti-carcinogenic effect of these drugs is
      not known, but results of most studies support that cyclooxygenase-2 (an
      inducible isoform of prostaglandin synthetase, COX-2) is a major target of NSAIDs
      in this effect. Recent immunohistochemical studies have revealed that COX-2 is
      expressed not in tumor cells but in interstitial cells of colonic adenomas.
      Accordingly, NSAIDs may exhibit anti-carcinogenic property through the inhibition
      of prostaglandin production by COX-2 expressing interstitial cells. Future
      research should be focused on the role of prostaglandins in the interaction of
      tumor cells and interstitial cells in colon carcinogenesis.

PMID- 11324435
TI  - Ras farnesyltransferase inhibition: a novel and safe approach for cancer
      chemotherapy.
AB  - The 21-kDa Ras proteins are well known for their regulatory role in oncogenic,
      mitogenic, and developmental signaling pathways. GTP activated Ras interacts
      directly with the Raf protein to recruit the MAP kinases and their subordinates.
      Attachment of Ras protein to the plasma membrane that requires farnesylation by
      farnesyl pyrophosphate at its C-terminus, is essential for its biological
      activity. Ras oncogenes are associated with a wide variety of solid tumors and
      leukemias for which existing chemotherapeutics have limited utility. A promising
      pharmacological approach of antagonizing oncogenic Ras activity is to develop
      inhibitors of farnesyl transferase. These inhibitors may be useful in blocking
      the action of Ras onco-proteins.

PMID- 11324436
TI  - Antagonism of LPS and IFN-gamma induced iNOS expression in human atrial
      endothelia by morphine, anandamide, and estrogen.
AB  - AIM: To determine whether inducible nitric oxide synthase (iNOS) stimulation of
      human atrial fragments can be diminished by the naturally occurring signal
      molecules, such as morphine, anandamide, and estrogen. The use of iNOS as an
      indicator is justified since it has been associated with initiation of various
      types of cellular damage either directly or indirectly. METHODS: Western blots
      were performed on control and drug-exposed atrial tissue before and after
      lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) exposure. RESULTS:
      Preincubation of the tissue with morphine, anandamide or estrogen prior to, but
      not after, the addition of LPS + IFN-gamma, blocked iNOS expression. The nitric
      oxide donor SNAP also blocked iNOS induction while preincubation of atrial
      fragments with an inhibitor of NOS, L-NAME, prior to morphine or anandamide
      exposure, restored LPS + IFN-gamma induction of iNOS. CONCLUSION: These data
      suggest a direct regulatory link at the transcriptional level between
      constitutive (c) NOS and iNOS in human atrial tissue.

PMID- 11324437
TI  - Indirect neurotrophic effect of neuropeptide ZNC(C)PR on PC12 cells via peptide
      stimulation of C6 cells.
AB  - AIM: To understand the mechanism of neurotrophic action of neuropeptide ZNC(C)PR
      and its effect on which could affect both growth and apoptosis of C6 cells.
      METHODS: Effects of ZNC(C)PR-treated C6 conditioned medium was observed on on
      culture of PC12 cells. The development of PC12 cells was determined by ratio of
      neurite-bearing cells in the total cells. The specific binding of ZNC(C)PR on C6
      cells was determined by radioligand binding assay (RBA). RESULTS: ZNC(C)PR
      treated C6 conditioned medium increased the ratio of neurite-bearing PC12 cells
      by 36% compared to the untreated C6 conditioned medium or to a mixture of
      ZNC(C)PR with the untreated C6 conditioned medium. RBA showed a specific binding
      site of ZNC(C)PR on C6 cells with Kd value of 2.74 nmol.L-1 and Bmax value of 19
      pmol.g-1 protein. CONCLUSION: ZNC(C)PR enhanced C6 cells induced secretion of
      some neurotrophic factors which acted as enhancers for PC12 cells
      differentiation, through its specific receptor sites on the neuroglioma cell.

PMID- 11324438
TI  - Protective effect of bilobalide against nitric oxide-induced neurotoxicity in
      PC12 cells.
AB  - AIM: To examine the effects of bilobalide on nitric oxide-induced neurotoxicity
      in pheochromocytoma-derived PC12 cells (PC12 cells). METHODS: PC12 cell survival
      was monitored by LDH release and 3-(4, 5-dimethylthiazol-2-yl)-2, 5
      diphenyltetrazolium bromide (MTT) assays. Superoxide dismutases (SOD) and
      catalase (CAT) activities were measured based on their abilities to inhibit the
      oxidation of epinephrine by the xanthine-xanthine oxidase system or to decompose
      H2O2 respectively. The content of malondialdehyde (MDA) was measured by a
      fluorometric assay to indicate the lipid peroxidation. RESULTS: 3
      Morpholinosydnonimine (SIN-1, 50-300 mumol.L-1) induced PC12 cell damage. After
      the cells had been pretreated with 10 mumol.L-1 bilobalide for 24 h, the cell
      viability was increased to 91% +/- 30% from 52% +/- 14% in SIN-1 alone group.
      Moreover, the activities of SOD and CAT were increased after cells were treated
      with bilobalide. CONCLUSION: The NO-induced neurotoxicity can be protected by
      bilobalide in PC12 cells. The bilobalide-induced increase in SOD and CAT
      activities may serve as one of the mechanisms underlying the neuroprotective
      effect of bilobalide.

PMID- 11324439
TI  - Effect of melatonin on pro-opiomelanocortin mRNA expression in arcuate nucleus of
      rat hypothalamus.
AB  - AIM: To observe altered expression of pro-opiomelanocortin (POMC) mRNA localized
      in neurons in the arcuate nucleus of rat hypothalamus following exogenous
      administration of melatonin. METHODS: The experimental animals were divided into
      two groups injected i.p. with melatonin 90 mg.kg-1 and vehicle at 12 h interval
      (9:00 am and 9:00 pm). Twelve hours after the last injection, the rat brains were
      processed for coronal sections and nonradioactive in situ hybridization
      histochemistry technic was used. The integral optical density (IOD) and mean
      optical density (OD) of the stained brain sections were measured using the
      computer-assisted image processing technique. RESULTS: The POMC mRNA expression
      in the arcuate nucleus showed obvious enhancement in the brain sections of rats
      treated with melatonin. The IOD and OD values in the hypothalamic arcuate nucleus
      area were increased significantly (P < 0.01, P < 0.05 respectively) with
      melatonin treatment. CONCLUSION: Melatonin may enhance the POMC mRNA expression
      in the arcuate nucleus of rat hypothalamus.

PMID- 11324440
TI  - A transient increase in CCK mRNA levels in hippocampus following audiogenic
      convulsions in audiogenic seizure-prone rats.
AB  - AIM: To examine the effects of a single convulsion and multiple convulsions on
      cholecystokinin (CCK) mRNA expression in hippocampus of audiogenic seizure-prone
      rats (P77PMC). METHODS: Ringing (electric bell, 100 dB, 60 s) was used to induce
      convulsions, hippocampal CCK mRNA expression was exhibited by in situ
      hybridization. RESULTS: 1) The number of CCK mRNA-positive neurons in principal
      hippocampus of normal rats was 34 +/- 5, which elevated markedly after a single
      (155 +/- 7, P < 0.01) or multiple convulsions (95 +/- 8, P < 0.01). 2) CCK mRNA
      levels in multiple consecutive convulsion rats were lower than that in a single
      convulsion rats (P < 0.01). CONCLUSION: The increased number of CCK mRNA-positive
      neurons in hippocampus may have important functional consequences in convulsion
      associated processes.

PMID- 11324441
TI  - Long-term potentiation induced by nicotine in CA1 region of hippocampal slice is
      Ca(2+)-dependent.
AB  - AIM: To observe the effects of Ca2+ on hippocampal long-term potentiation (LTP)
      induced by nicotine in CA1 region of rat hippocampal slice. METHODS:
      Extracellularly recorded population spikes (PS) of the pyramidal cell layer in
      the hippocampal CA1 region in vitro. RESULTS: Nicotine 1 mumol.L-1 induced LTP in
      the hippocampal CA1 region. It did not induce LTP in CA1 region when CA2+ was
      removed from artificial cerebrospinal fluid (ACSF). Nifedipine 1 and 10 mumol.L-1
      partly inhibited LTP induced by nicotine, and thapsigargin 1 and 10 mumol.L-1
      completely inhibited LTP induced by nicotine. CONCLUSION: LTP induced by nicotine
      in hippocampal CA1 region is Ca(2+)-dependent. Both Ca2+ influx and Ca2+ release
      participate in the induction of LTP.

PMID- 11324442
TI  - Inhibitory effects of chiral 3-n-butylphthalide on inflammation following focal
      ischemic brain injury in rats.
AB  - AIM: To evaluate the degree of neutrophil infiltration into ischemic tissue after
      transient focal cerebral ischemia, and to examine the effects of chiral 3-n
      butylphthalide (NBP) on this inflammatory process. METHODS: After a 24-h
      reperfusion following transient cerebral ischemia, two different techniques,
      histologic analysis and modified myeloperoxidase (MPO)-quantification method,
      were utilized to identify the infiltration of neutrophils into cerebral tissue
      following ischemia. The expression of intercellular adhesion molecule-1 (ICAM-1)
      and tumor necrosis factor-alpha(TNF-alpha) in the ischemic zone were observed by
      immunohistochemistry, Western blot, and in situ hybridization techniques.
      RESULTS: In cerebral cortex area perfused by middle cerebral artery (MCA), MPO
      activity was greatly increased after 24 h of reperfusion in the vehicle group,
      and it correlated well with the infiltration of neutrophils. Administration of dl
      , d-, and l-NBP (20 mg.kg-1) partially inhibited both the increase in MPO
      activity and the appearance of neutrophils in ischemia-reperfusion sites. Up
      regulation of ICAM-1 was also observed on the microvessel endothelium in the
      ischemic territory. In addition, chiral NBP markedly blunted ICAM-1 expression,
      and decreased the number of TNF-alpha blue purple-positive neurons induced by
      ischemia-reperfusion injury. CONCLUSION: The results indicate that the increase
      in neutrophils infiltration into the infarct site implicated postischemic brain
      injury, and NBP was effective in protecting the ischemic sites following ischemic
      insult.

PMID- 11324443
TI  - Arcuate nucleus of hypothalamus involved in analgesic action of l-THP.
AB  - AIM: To study the role of the arcuate nucleus of hypothalamus in analgesic action
      of l-tetrahydropalmatine (l-THP). METHODS: The horseradish peroxidase (HRP)
      retrograde tracing, HRP retrograde tracing combined with immunohistochemistry,
      lesion of nucleus, tail-flick test, and intra-PAG injection were used in the
      present study. RESULTS: HRP retrograde tracing results showed that the striatum
      or accumbens nucleus connect with PAG by two pathways: 1) striatum or accumbens
      nucleus-->arcuate nucleus-->PAG; 2) striatum or accumbens nucleus-->habenula-
      >PAG. It was found that neurons in the arcuate nucleus projecting to PAG were
      mainly beta-endorphin neurons as observed by HRP retrograde tracing combined with
      immuno-histochemistry. After lesion of the arcuate nucleus, the analgesic action
      of l-THP (40 mg.kg-1, i.p.) was abolished, while lesion of the habenula had no
      such effect. Moreover, intra-PAG injection of naloxone (2, 3 micrograms) could
      markedly attenuate the analgesic action of l-THP (40 mg.kg-1, i.p.) in a dose
      dependent manner. CONCLUSION: beta-Endorphin neurons in the arcuate nucleus play
      an important role in the analgesic action of l-THP.

PMID- 11324444
TI  - Dimethylamiloride-induced differentiation of HL-60 cells.
AB  - AIM: To study the effect of 5-(N,N-dimethyl) amiloride (DMA) on the proliferation
      and differentiation of HL-60 cells in vitro. METHODS: MTT assay to test
      cytotoxicity; cell staining and NBT reduction to test cell differentiation.
      RESULTS: DMA inhibited HL-60 cells growth in a concentration-dependent manner,
      and IC50 value for 96 h was 31.7 (95% confidence limits: 6.3-57.1) mumol.L-1. DMA
      also induced granulocytic differentiation in HL-60 cells. The percentage of
      differentiating cells increased from 6.5% to 70% after DMA 100 mumol.L-1
      treatment for 3 d. The differentiating effect of DMA was distinguishable from
      amiloride, 5-(N-ethyl-N-isopropyl)amiloride (EIPA), and (5-(N-ethyl-N
      isopropyl)amiloride (MIA). None among the amiloride, EIPA, and MIA were capable
      of triggering the differentiation of HL-60 cells. CONCLUSION: DMA inhibited the
      proliferation of HL-60 cells and induced differentiation of HL-60 cells.

PMID- 11324445
TI  - Anti-hepatoma activity of taxol in vitro.
AB  - AIM: To investigate the in vitro anti-hepatoma activity of taxol against SMMC
      7721 human hepatoma cells. METHODS: The hepatoma cell growth was measured by MTT
      microculture tetrazolium assay. Cell-cycle kinetics and apoptosis were analyzed
      by flow cytometry and microscopic examination. RESULTS: Taxol inhibited the
      hepatoma cell growth in concentration- and time-dependent manners with IC50 of
      18.96 nmol.L-1. Marked cell accumulation in G2/M phase and multinucleated cells
      were also observed after treatment with taxol 10 nmol.L-1. In addition, taxol at
      10 nmol.L-1 could induce the apoptosis of hepatoma cells. CONCLUSION: Taxol
      suppresses the growth of SMMC-7721 human hepatoma cells in vitro by causing cell
      cycle arrest, aberrant mitosis, and apoptosis of the human hepatoma cells.

PMID- 11324446
TI  - Ebselen protection against hydrogen peroxide-induced cytotoxicity and DNA damage
      in HL-60 cells.
AB  - AIM: To study the protective effect of ebselen (Ebs) on hydrogen peroxide (H2O2)
      induced cytotoxicity and DNA damage in human leukemia cell line HL-60. METHODS:
      The inhibitory effect of H2O2 on cell growth was determined using the tetrazolium
      dye colorimetric test, and the lipid peroxidation was estimated by
      malondialdehyde (MDA) formation. DNA damage was detected using single cell gel
      electrophoresis, and intracellular reactive oxygen species (ROS) formation was
      measured using a fluorescent probe, 2',7'-dichlorofluorescin diacetate (DCFH-DA).
      RESULTS: H2O2 (100 mumol.L-1) suppressed the growth of HL-60 cells and the
      addition of Ebs (1-20 mumol.L-1) reduced the suppression in a concentration
      dependent manner. Furthermore, Ebs also displayed a concentration-dependent
      reduction of MDA formation in H2O2-treated cells, at the concentration of 20
      mumol.L-1 the inhibitory rate was 56.4%. Ebs was able to reduce the ROS formation
      and DNA damage caused by H2O2 in a concentration-dependent manner. CONCLUSION:
      Ebs has a strong protective ability against the cytotoxicity and DNA damage
      caused by reactive oxygen species (ROS).

PMID- 11324447
TI  - Antagonistic effect of 3,6-dimethamidodibenzopyriodonium gluconate on lipid
      peroxidation in cerebral cortical neuronal cultures and rat brains during focal
      cerebral ischemia reperfusion.
AB  - AIM: To study 3,6-dimethamidodibenzopyriodonium gluconate (I-93) antagonistic
      effects on lipid peroxidation in cerebral cortical neuronal cultures and rat
      brains during focal cerebral ischemia-reperfusion. METHODS: Cerebral cortical
      neurons were cultured and rat focal cerebral ischemia-reperfusion model was
      established by reversible middle cerebral artery occlusion (MCAO) without
      craniectomy. The efflux of lactate dehydrogenase (LDH) from neurons, content of
      malondialdehyde (MDA) in neurons and brain homogenate, activity of superoxide
      dismutase (SOD) in brain homogenate, and index of cerebral edema as well as brain
      morphology were investigated. RESULTS: I-93 10-40 mumol.L-1 concentration
      dependently inhibited efflux of LDH and elevated levels of MDA induced by
      addition of H2O2(10 mumol.L-1) in vitro. I-93 0.5 mg.kg-1 improved the cerebral
      morphology, reduced brain edema, decreased MDA content, and enhanced SOD activity
      in brain homogenate. CONCLUSION: I-93 protects neurons from H2O2-induced
      neurotoxicity and ischemia-reperfusion mediated damage by increasing the activity
      of antioxidant enzymes and suppressing the generation of lipid peroxides.

PMID- 11324448
TI  - Salvianolic acid B protects brain against injuries caused by ischemia-reperfusion
      in rats.
AB  - AIM: To study the protective effects of salvianolic acid B (Sal B) against the
      ischemia-reperfusion induced rat brain injury. METHODS: Focal cerebral ischemia
      reperfusion model in rats was employed to study the protective effects of Sal B.
      The behavioural tests were used to evaluate the damage to the central nervous
      system. Spectrophotometric assay methods were used to measure the activity of
      superoxide dismutase (SOD), contents of reduced glutathione (GSH),
      malondialdehyde (MDA), adenosine 5-triphosphorate (ATP), and lactate acid (LA) in
      experimental rats' brain homogenate. RESULTS: Focal cerebral ischemia-reperfusion
      resulted in abnormal behavior which could be alleviated by Sal B 10 mg.kg-1 i.v.,
      and nimodipine (Nim) 4 mg.kg-1 i.p. At the same time, Sal B 10 mg.kg-1 and Nim 4
      mg.kg-1 could inhibit the decrease in SOD, GSH, and ATP levels and the increase
      in MDA and LA levels caused by ischemia-reperfusion in brain. CONCLUSION: Sal B
      showed a protective action against the ischemia-reperfusion induced injury in rat
      brain by reducing lipid peroxides, scavenging free radicals and improving the
      energy metabolism.

PMID- 11324449
TI  - Intermittent hypoxia exposure-induced heat-shock protein 70 expression increases
      resistance of rat heart to ischemic injury.
AB  - AIM: To quantify the levels of HSP70 induced by different durations of
      intermittent (high altitude) hypoxia and to correlate them with the degree of
      protection of the rat heart from ischemic injury. METHODS: Reverse transcriptase
      polymerase chain reaction (RT-PCR) was used to detect the level of HSP70 mRNA
      expression in rat myocardium. Ischemia/reperfusion injury was presented as
      severity of arrhythmias induced by occlusion and reperfusion of the left anterior
      descending coronary artery of rat heart. RESULTS: The level of HSP70 mRNA
      expression increased progressively along with the duration of intermittent
      hypoxia training. It was 2.6, 3.6, and 3.8 folds after 14-, 28-, and 42-d
      exposures compared to that of normoxia. The tolerance of rat heart to
      ischemia/reperfusion injury increased with hypoxia pretreatment. Such an effect
      was significant after rat were exposed to a 28-d intermittent hypoxia (IH). The
      scores for ischemia and reperfusion inducing arrhythmia for 28- and 42-d IH were
      1.2 +/- 0.5, 1.0 +/- 0.5 and 1.0 +/- 0.5, 0.9 +/- 0.5 (P < 0.01 compared with 4.0
      +/- 0.7, 3.3 +/- 0.6 in normoxia rats). The overexpression of HSP70 and the
      increased tolerance to subsequent acute ischemia/reperfusion injury could last
      for 2 wk after the rats (subjected to 28 d IH) returned to normoxia. Furthermore,
      there was a reverse correlation between the amount of HSP70 induced and the
      arrhythmia occurrence (r = -0.98, -0.92 for ischemia and reperfusion induced
      arrhythmia, P < 0.01). CONCLUSION: These results suggest that increased
      resistance of rat heart to ischemia/reperfusion injury after intermittent hypoxia
      exposure may be related to the amount of HSP70 induced.

PMID- 11324450
TI  - Effect of lipanthyl on mRNA expression of endothelin-1 and nitric-oxide synthase
      in atherosclerotic vessel wall in rabbits.
AB  - AIM: To study the mechanism of regression of atherosclerosis (AS) by lipanthyl.
      METHODS: Experimental atherosclerotic rabbits created by damaging the abdominal
      aortic endothelium and feeding with high fat diet for 8 wk were then treated with
      lipanthyl 15 mg.kg-1.d-1 for 16 wk. Expression of endothelin (ET)-1 mRNA and
      nitric oxide synthase (NOS) mRNA in atherosclerotic vessel wall was measured by
      in situ hybridization and reverse transcription polymerase chain reaction (RT
      PCR), respectively. RESULTS: After lipanthyl administration for 16 wk, ET-1 mRNA
      expression was reduced, and integral optical density (IOD) and area of
      hybridization granule were observed to be (49,113 +/- 16,868) and (2448 +/- 621)
      micron 2 in lipanthyl group and (65,188 +/- 10,113) and (3028 +/- 352) micron 2
      in atherosclerotic group, respectively. Regarding inducible NOS mRNA expression,
      IOD and area were decreased by 25.5% and 53.3%, respectively, whereas endothelial
      NOS mRNA expression was increased. CONCLUSION: Restoration of the disturbed ET-1
      mRNA/NOS mRNA balance by lipanthyl might be one of its mechanisms leading to
      regression of atherosclerosis.

PMID- 11324451
TI  - Tetrahydroprotoberberines inhibit lipid peroxidation and scavenge hydroxyl free
      radicals.
AB  - AIM: To study the effects of tetrahydroprotoberberines (THPB) on rat liver and
      brain lipid peroxidation (LPO) and oxygen free radicals generation. METHODS: The
      malondialdehyde (MDA) levels in rat brain and liver homogenates, induction of MDA
      by Fe(2+)-Vit C in mitochondria, OH. generation by Fenton reaction, and O2.-
      generation by pyrogallol oxidation were observed in vitro. RESULTS: (1) THPB
      lowered the MDA contents in the liver homogenate and mitochondria, and the IC50
      values of l-THPB-18 and l-stepholidine (SPD) in the liver mitochondria were 3.1
      and 12.7 mumol.L-1 respectively. SPD decreased the MDA contents in the brain
      homogenate and mitochondria with IC50 values of 102 and 35.0 mumol.L-1
      respectively. (2) THPB scavenged OH., and the IC50 values of l-THPB-18 and SPD
      were 0.21 and 3.8 mumol.L-1 respectively, but no effect on O2.- was observed.
      CONCLUSION: THPB could reduce the MDA contents and scavenge OH. and THPB-18 was
      the most potent amongst them.

PMID- 11324452
TI  - Vulnerable substrate and multiple ion channel disorder in a diseased heart will
      be new targets for antiarrhythmic therapy.
AB  - Life-threatening arrhythmia remains a problem contributing to major death in
      cardiovascular diseases. Till date the antiarrhythmic drugs (AAD) including the
      Class I and the pure Class III agents have not been recommended for controlling
      malignant ventricular arrhythmias in a diseased heart, not because of low
      efficacy but because of an increase in mortality due to their toxic effects. A
      vulnerable substrate (VS) possessing some properties such as reduced NE and SOD
      activity, hypertrophied myocardium, and an increase in QT dispersion, is reported
      to develop in non-infarcted zone of an infarcted heart. Hypertrophied ventricle
      and exaggerated cardiac arrhythmia can be produced on chronic medication with
      levothyroxin and this model shares some properties of VS. There is a significant
      difference in the pattern of disordered ion channels between the congenital long
      QT syndrome(LQTS) and the acquired heart disease. The affected ion channel in
      congenital LQTS is single. A novel mutation causing an early appearance of stop
      codon was discovered in HERG gene resultant with a single disarranged IKr channel
      leading to a prolonged QT interval. In contrast it is characterised with multi
      channels and non-specific disorder in the hypertrophied myocardium in the
      acquired heart disease. The disordered ion channel is the consequence of the VS
      lesion influencing the lipid membrane in a diseased heart. The VS and multiple
      ion channel disorder are provided as new targets to treat cardiac arrhythmias in
      a diseased heart.

PMID- 11324453
TI  - Alteration of basic fibroblast growth factor expression in rat during cerebral
      ischemia.
AB  - AIM: To investigate the distribution and expression changes of basic fibroblast
      growth factor (bFGF)-like immunoreactivity (IR) in focal cerebral ischemic rat
      brain. METHODS: The expression of bFGF was observed by fluoro
      immunohistochemistry. The focal cerebral ischemic injury was carried out using
      middle cerebral artery occlusion (MCAO) model. RESULTS: Confocal images
      demonstrated that both the striatum and the frontoparietal cortex showed
      increases of bFGF-like IR after 2-h MCAO and 24-h reperfusion. In striatum, the
      increase patterns of bFGF-like IR were different according to the ischemic
      extent. In the core of infarct and its surrounding region (with more IR
      induction), bFGF-like IR was mainly located in astrocytes. In region adjacent to
      infarct (with most IR induction, the grey ratio of bFGF-like IR increased from
      sham-98% +/- 10% to ischemia-125% +/- 6%), some neurons also showed an
      upregulation of bFGF-like IR. In frontoparietal cortex, strong induction of bFGF
      like IR was mostly seen in neurons (The grey ratio of bFGF-like IR increased from
      sham-104% +/- 11% to ischemia-132% +/- 28%), although it was observed in
      astrocytes as well. CONCLUSION: The expression of bFGF increased after focal
      cerebral ischemia in rats, suggesting that: in striatum, astrocytes may play an
      important role in the protection of neurons via the overexpression of bFGF;
      whereas in cortex, neurons probably exert an autoprotection through expressing
      bFGF themselves.

PMID- 11324454
TI  - Inhibitory effect of 1-(2, 6-dimethylphenoxy)-2-(3, 4-dimethoxyphenyl-ethylamino)
      propane hydrochloride on inward rectifier and delayed rectifier K+ currents in
      guinea pig ventricular myocytes.
AB  - AIM: To study the effects of 1-(2,6-dimethylphenoxy)-2-(3,4-dimethoxyphenyl
      ethylamino) propane hydrochloride (DDPH) on action potential (AP), inward
      rectifier K+ current (IK1), and delayed rectifier K+ current (IK) in isolated
      guinea pig ventricular myocytes. METHODS: Whole cell patch-clamp recording
      techniques. RESULTS: DDPH 0.1-100 mumol.L-1 decreased 50% duration of action
      potential (APD50) concentration-dependently. APD50 was shortened from (493 +/-
      58) to (262 +/- 38) ms (n = 7 cells from 5 guinea pigs, P < 0.01) by DDPH 10
      mumol.L-1. However, 90% duration of action potential (APD90) was increased by
      DDPH (> 1 mumol.L-1). At high concentration (> 10 mumol.L-1) DDPH decreased
      resting membrane potential (RP) and amplitude of action potential (APA). DDPH
      inhibited tail current of IK (IK.tail) concentration-dependently, 46% at 10
      mumol.L-1 and 78% at 100 mumol.L-1. EC50 for DDPH inhibiting IK was 13.3 (11.6
      16.7) mumol.L-1. DDPH also blocked IK1. DDPH at high concentration (> 10 mumol.L
      1) shifted the reverse potential of IK1 positively. All the effects of DDPH were
      reversible after washout. CONCLUSION: DDPH blocked both IK1 and IK current in
      guinea pig ventricular myocytes.

PMID- 11324455
TI  - Determination of idebenone in plasma by HPLC/MS.
AB  - AIM: To develop a sensitive method for the analysis of idebenone [Ide, 6-(10
      hydroxydecyl)-2,3-dimethoxy-5-methyl-p-benzoquinone] in human plasma. METHODS:
      The concentrations in plasma were determined by a high performance liquid
      chromatography-mass spectrometry coupled with an atmosphere pressure chemical
      impact ion source method (LC/MS-APCI). RESULTS: The chromatograms indicated a
      good separation of the analytes and there was no interference by other compounds.
      The coefficients of determination of the calibration curves were above 0.999. The
      calibration range was 20-600 micrograms.L-1. Peak plasma idebenone concentration
      (Cmax) of (316 +/- 85) micrograms.L-1 was achieved within (96 +/- 34) min (Tpeak)
      after an oral dose of 30 mg. Lower limit of quantitation of the method for Ide
      determination was 20 micrograms.L-1. CONCLUSION: The advantages of using LC/MS
      APCI technique include better sensitivity, higher selectivity, and less time
      consumption, compared with HPLC method.

PMID- 11324456
TI  - Different mechanisms mediate beta adrenoceptor stimulated vasorelaxation of
      coronary and femoral arteries.
AB  - AIM: To determine whether different mechanisms mediate vasorelaxation of swine
      coronary and femoral arteries induced by beta adrenoceptor stimulation. METHODS:
      The organ-bath was used to observe the tension changes in rings of coronary and
      femoral arteries to different concentrations of isoprenaline (ISO) after
      endothelium removal, nitric-oxide synthase (NOS) inhibition by L-NMMA and beta 1
      and/or beta 2 adrenoceptor antagonization. RESULTS: Endothelium removal, NOS
      inhibition, beta 2 adrenoceptor antagonization did not change the vasorelaxation
      induced by ISO in coronary artery, however, abolished the vasorelaxation in
      femoral artery. beta 1 Adrenoceptor antagonization did not change the tension of
      femoral artery, but abolished the ISO induced vasorelaxation of coronary artery.
      CONCLUSIONS: Vasorelaxing effect of ISO in swine coronary artery is mediated
      through beta 1 adrenoceptor and not through L-arginine/nitric oxide pathway,
      however, in femoral artery, it is mediated through beta 2 adrenoceptor and L
      arginine/nitric oxide pathway.

PMID- 11324457
TI  - Prevention of intima hyperplasia by mitogen-activated protein kinase antisense
      oligodeoxynucleotide.
AB  - AIM: To investigate the preventive effect of Ca(2+)-calmodulin dependent kinase
      (CCDPK) (formerly: mitogen-activated protein kinase or MAPK) antisense
      phosphorothioate oligodeoxynucleotide (ODN) on vascular smooth muscle cell (VSMC)
      proliferation in vitro and on intima hyperplasia after injury in vivo. METHODS:
      Liposomal transfection was used to introduce phosphorothioate-protected 17-mer
      antisense CCDPK ODN directed against the initiation of translation sites of the
      p42 and p44 CCDPK isoforms into cultured rat VSMC to deplete CCDPK and DNA
      synthesis induced by endothelin-1 (ET) or platelet derived growth factor (PDGF).
      A 17-mer sense and a random sequence CCDPK ODN were used as controls. CCDPK
      protein p44 and p42 levels were measured by Western blot. DNA synthesis was
      measured by [3H]thymidine incorporation. In in vivo study, rat balloon
      angioplasty was performed by a 2F Fogarty catheter. The antisense CCDPK ODN 200
      micrograms was administered to the adventitial surface of the injured carotid
      artery by pluronic gel 30% (w/v) solution. Two weeks after vascular injury,
      carotid arteries were removed and cross sections were made and stained with
      hematoxylin/eosin for patho-histological examination. Fluorecein isothiocynate
      (FITC)-labeled and phosphorothioate-protected ODN was used to detect the uptake
      of ODN in vitro and in vivo. RESULTS: CCDPK antisense ODN (0.4 mumol.L-1) reduced
      p42/p44 protein expression and inhibited VSMC [3H]thymidine incorporation
      stimulated by ET and PDGF. Antisense CCDPK ODN treatment at 2 wk after injury
      resulted in a significant inhibition of intima hyperplasia, compared with
      untreated vessels. CONCLUSION: The p42/p44-CCDPK antisense ODN inhibits in vitro
      stimulated rat VSMC proliferation and in vivo injured arterial intima
      hyperplasia.

PMID- 11324458
TI  - Antisense IRAK-2 oligodeoxynucleotide inhibits interleukin-1-induced nuclear
      factor-kappa B activation in vitro.
AB  - AIM: To study the inhibitory effects of antisense interleukin-1 receptor
      associated kinase-2 (IRAK-2) oligodeoxynucleotide (ODN) on interleukin-1 (IL-1)
      stimulated nuclear factor-kappa B (NF-kappa B) activation. METHODS: Antisense
      IRAK-2 ODN was delivered by lipofectin encapsulation into human embryonic kidney
      293 cells (HEK 293 cells). The levels of NF-kappa B were assayed by sandwich
      ELISA. RESULTS: (1) Treatment of HEK 293 cells with IL-1 enhanced NF-kappa B
      level in nuclei by 518.5% +/- 2.1%. (2) Antisense IRAK-2 ODN inhibited IL-1
      induced NF-kappa B activation in a concentration (1-8 micrograms)- and time (5-24
      h)-dependent manner. A maximum inhibition was 70.7% +/- 1.0% from Acontrol 0.834
      +/- 0.014 to 0.244 +/- 0.008 after treatment with antisense IRAK-2 ODN 4
      micrograms for 8 h. CONCLUSION: Antisense IRAK-2 ODN inhibited IL-1-induced NF
      kappa B activation.

PMID- 11324459
TI  - Phosphatidylinositol 3-kinase modulates IL-18-induced nuclear factor-kappa B
      activation.
AB  - AIM: To investigate whether phosphatidylinositol (PI) 3-kinase is involved in
      interleukin-18 (IL-18)-induced nuclear factor-kappa B (NF-kappa B) activation.
      METHODS: Antisense PI 3-kinase oligonucleotide (ODN) was delivered by lipofectin
      encapsulation into cultured human hepatocellular carcinoma HepG2 cells. PI 3
      kinase mRNA expression was assayed by semiquantitative reverse transcription-PCR.
      The levels of NF-kappa B were measured by sandwich ELISA. RESULTS: (1) Antisense
      PI 3-kinase ODN blocked PI 3-kinase mRNA expression. (2) IL-18 activated NF-kappa
      B from basal level of 0.153 +/- 0.008 to 1.942 +/- 0.017. (3) Antisense PI 3
      kinase ODN inhibited IL-18-induced NF-kappa B activation in a concentration (1-8
      mg/L)- and time (5-24 h)-dependent fashion. When the cells were treated with
      antisense PI 3-kinase ODN 2 mg/L for 8 h, a maximum inhibitory rate was 35.2%
      from 1.942 +/- 0.017 control to 1.259 +/- 0.018. CONCLUSION: PI 3-kinase is
      necessary for IL-18-stimulated NF-kappa B activation.

PMID- 11324460
TI  - High glucose inhibits expression of inducible and constitutive nitric oxide
      synthase in bovine aortic endothelial cells.
AB  - AIM: To investigate the effects of high glucose on the expression of nitric-oxide
      synthase (NOS) in cultured bovine aortic endothelial cells (BAEC). METHODS: BAEC
      were cultured and passaged in normal glucose (NG) 5.5 mmol.L-1, high glucose (HG)
      25 mmol.L-1, or high osmolarity (glucose 5.5 mmol.L-1 + mannitol 19.5 mmol.L-1,
      Mann-BAEC), lipopolysaccharides (LPS)-induced nitric oxide (NO) production was
      assessed by Griess reaction. The expression of inducible NOS (iNOS) and
      constitutive NOS (ecNOS) was determined by Western blot. RESULTS: At a
      concentration range from 0.5 to 2 mg.L-1, LPS stimulated NO production in NG-BAEC
      in a concentration-dependent manner. NO production reached the peak level at LPS
      1 mg.L-1. HG inhibited NO production, when compared with NG- and Mann-BAEC
      (nitrite mumol.L-1: HG-BAEC 43 +/- 8, vs NG-BAEC 71 +/- 11, Mann-BAEC 70 +/- 9, n
      = 4 experiments, P < 0.01). iNOS expression was decreased by 39.9% and 39.3%, and
      ecNOS by 28% and 24% respectively in HG-BAEC, when compared with NG- or Mann
      BAEC. However, no marked difference was observed in the LPS-induced NO production
      and the expression of iNOS and ecNOS between NG- and Mann-BAEC. CONCLUSIONS:
      Inhibition of BAEC NO production by HG was mainly due to a decreased expression
      of NOS protein.

PMID- 11324461
TI  - Behavioral characteristics of olanzapine: an atypical neuroleptic.
AB  - AIM: To assess the atypical neuroleptic properties of a novel antipsychotic
      agent, olanzapine (Ola). METHODS: The action of Ola on apomorpine (Apo)-induced
      climbing behavior, 5-hydroxy-dl-tryptophan (5-HTP)-induced head twitch response,
      oxotremorine-induced tremor, and the conditioned avoidance behavior in mice were
      observed. The catalepsy of mice induced by Ola was also investigated. The single
      unit extracellular recording technique was used to compare the spontaneous firing
      rate changes of dopamine (DA) cells in the ventral tegmental area (VTA, A10) and
      the substantia nigra pars compact (SNC, A9) in rats after i.v. Ola. RESULTS: Ola
      antagonized the climbing behavior (ED50 1.8 mg.kg-1, p.o.), head twitch behavior
      (ED50 0.3 mg.kg-1, p.o.), and tremor (ED50 5.2 mg.kg-1, p.o.) in mice. In a
      conditioned avoidance paradigm in mice, Ola inhibited the avoidance response with
      an ED50 of 2.72 mg.kg-1 (p.o.). However, the catalepsy was not induced by Ola in
      mice even under a very high dose of 100 mg.kg-1 (p.o.). Ola selectively increased
      the firing rate of DA cells in the VTA, but failed to affect that of SNC DA
      cells. CONCLUSION: Ola distinguished itself from the typical neuroleptic (e.g.
      haloperidol, Hal) and took resemblance of the atypical neuroleptic (e.g.
      clozapine, Clo) in 3 aspects: 1) the multiple receptor pharmacodynamics involving
      D1/D2, 5-HT2 and M-ACh receptors; 2) dose-response separation between the block
      of conditioned avoidance response and catalepsy induction; and 3) the specificity
      of action sites of firing rates upon acute drug challenge.

PMID- 11324462
TI  - Preparation of monoclonal antibody against human m3 receptor.
AB  - AIM: To raise monoclonal antibody against human m3 receptor. METHODS: The m3
      receptor selective peptide segments deduced from its gene were chemically
      synthesized, coupled to keyhole limpet hemocyanin carrier protein, and injected
      to Balb/c mice to raise monoclonal antibody. Antibody was purified by a
      combination of two-step precipitation methods and ion-exchange chromatography.
      The specificity of monoclonal antibody was tested by enzyme-linked immunosorbent
      assay, immunohistochemistry, and radioligand binding assay of receptors. RESULTS:
      The monoclonal antibody specifically bound to the protein of rat salivary gland
      and m3 peptide, but not m4 peptide. In radioligand binding assay of receptors,
      monoclonal antibody inhibited the binding of 3H-QNB to muscarinic receptor in rat
      salivary gland, but not in rat heart, and could not inhibit the binding of 3H-PZ
      to rat brain cerebral cortex membrane protein. Immunohistochemical study showed
      that the human salivary cell surface was strongly stained, whereas the human
      heart cell surface was not. CONCLUSION: Highly purified (96.3%) monoclonal
      antibody against the m3 receptor peptide recognized the m3 receptor.

PMID- 11324463
TI  - Platelet-derived growth factor stimulated vascular smooth muscle cell
      proliferation and its molecular mechanism.
AB  - AIM: To study the molecular mechanism of platelet-derived growth factor (PDGF)-BB
      stimulated vascular smooth muscle cell (VSMC) proliferation. METHODS: DNA
      synthesis was measured by [3H]thymidine incorporation. Phosphorylation of the 42-
      and 44-kDa Ca(2+)-calmodulin dependent protein kinase (CCDPK) was measured by
      Western blotting method. The expression of c-myc specific mRNA was detected by in
      situ hybridization. RESULTS: PDGF-BB (2 micrograms.L-1) induced DNA synthesis and
      activated CCDPK in a concentration-dependent manner and a induced a marked c-myc
      mRNA expression. Egtazic acid (EGTA, 5 mmol.L-1), genistein (400 mumol.L-1) or PD
      98059 (50 mumol.L-1) reduced PDGF-BB (2 micrograms.L-1)-induced CCDPK activities
      and inhibited VSMC [3H]thymidine incorporation (P < 0.05). PD 98059 (50 mumol.L
      1) also inhibited PDGF-BB (2 micrograms.L-1)-induced c-myc mRNA expression.
      CONCLUSION: PDGF stimulated VSMC proliferation by activation of p44/p42 CCDPK,
      which is mediated by Ca2+ and protein tyrosine kinase (PTK), and up-regulation of
      c-myc mRNA expression.

PMID- 11324465
TI  - Effects of ascorbic acid and DL-alpha-tocopherol on human hepatoma cell
      proliferation and redifferentiation.
AB  - AIM: To examine the effects of ascorbic acid (AA) and DL-alpha-tocopherol (alpha
      T) on the proliferation and redifferentiation of human hepatoma cell. METHODS:
      Choosing an all-trans retinoic acid (RA) as a positive control, cell surface
      charge, biochemical changes, and cell growth in soft agar were measured. RESULTS:
      After treatment with AA 4 mmol.L-1 and alpha T 1 mmol.L-1 together, the growth
      curve and mitotic index of human hepatoma cells decreased remarkably, the
      cellular growth inhibitory rate amounted to 61.3%. The indices related to cell
      malignancy alleviated significantly; cell surface charge decreased, the
      electrophoresis rate dropped from 1.64 to 0.89 microns.s-1.V-1.cm-1, the average
      value of alpha-fetoprotein (alpha-FP) content decreased from 300 to 80
      micrograms.g-1 (protein), and gamma-glutamyl-transpeptidase (gamma-GT) activity
      decreased from 0.81 to 0.201 U.g-1(protein). The index related to cell
      differentiation increased significantly, such as the average level of tyrosine
      alpha-ketoglutarate transaminase activity increased from 10.6 to 45 micrograms.g
      1 (protein), and the colonogenic potential decreased by 96.6%. CONCLUSION: AA and
      alpha T combination inhibited human hepatoma cell proliferation, induced
      redifferentiation, and reversed its malignant phenotypic characteristics.

PMID- 11324464
TI  - Effect of anti-digoxin antiserum on endoxin and membrane ATPase activity in
      hypoxia-reoxygenation induced myocardial injury.
AB  - AIM: To evaluate the protective effect of anti-digoxin antiserum on hypoxia
      reoxygenation induced injured myocardium and its mechanism. METHODS: Anti-digoxin
      antiserum of different concentrations was used, its effect on endoxin and ATPase
      activity in cell membrane in hypoxia-reoxygenation myocardium model was observed.
      RESULTS: The level of endoxin was remarkably higher, ATPase activities in cell
      membrane were remarkably lower in hypoxic group and hypoxia-reoxygenation injury
      group than those of normal group; anti-digoxin antiserum could resume ATPase
      activity in a concentration-dependent manner. CONCLUSION: Rise of endoxin was the
      molecular biological basis of myocardial damage during myocardial hypoxia
      reoxygenation. Anti-digoxin antiserum had lessened myocardial injury and had a
      protective effect on hypoxia-reoxygenation myocardium by antagonizing effect of
      endoxin.

PMID- 11324466
TI  - Effects of Scutellarein on diabetic rat aorta.
AB  - AIM: To study the effect of Scutellarein (Scu) on the diabetic rat aorta.
      METHODS: Contractile responses to phenylepherine and endothelium-dependent
      relaxation responses to acetylcholine (ACh) in rat aorta were investigated after
      streptozocin-induced 6-wk diabetes, Scu-treated streptozocin-induced diabetes,
      and in age-matched control in vitro. RESULTS: 1) Endothelium-dependent relaxation
      to ACh in diabetic rats was decreased (P < 0.01) compared with age-matched
      control. 2) Contractile responses to phenylepherine were increased (P < 0.01) in
      diabetic rats. 3) The dietary supplement of 0.5% Scu starting from 1-wk diabetes
      induction prevented endothelial dysfunction (P < 0.01), but the contractile
      responses to phenylepherine were further increased. CONCLUSION: Scu prevented
      vascular endothelial dysfunction in diabetic rats, and also potentiated the
      contraction induced by phenylepherine.

PMID- 11324467
TI  - Protective action of piperine against experimental gastric ulcer.
AB  - AIM: To study the effects of piperine (Pip) on several experimental gastric
      ulcers in rats and mice. METHODS: The gastric mucosa damage was induced by
      stress, indometacin, HCl, and pyloric ligation in rats or mice. The number of
      gastric ulcers, the volume and acidity of gastric juices, and pepsin A activity
      were detected. RESULTS: Pip 25, 50, 100 mg/kg ig protected animals from gastric
      ulceration in a dose-dependent manner. The inhibitory rates were 16.9%, 36.0%,
      and 48.3% in stress ulcers; 4.4%, 51.1%, and 64.4% in indometacin ulcers; 19.2%,
      41.5%, and 59.6% in HCl ulcers; 4.8%, 11.9%, and 26.2% in pyloric ligation
      ulcers, respectively; Pip inhibited the volume of gastric juice, gastric acidity,
      and pepsin A activity. CONCLUSION: Pip has the protective effects against gastric
      ulceration.

PMID- 11324468
TI  - Protective effects of fructose-1,6-diphosphate against cerebral injury induced by
      subacute carbon monoxide intoxication in mice.
AB  - AIM: To study the effects of fructose-1,6-diphosphate (FDP) on delayed cerebral
      injury in mice from subacute carbon monoxide (CO) exposure. METHODS: Mice were
      exposed to CO (100 mL/kg i.p.) once a day, continouUsly for 7 d. After 7-d CO
      exposure, mortality of mice, changes in learning ability and memory using passive
      avoidAnce test, the pathomorphologic observation of brain tissue slices, and
      changes in monoamine oxide (MAO)-B activities in cerebral tissue were studied.
      FDP was administrated 30 min before CO-exposure every time. RESULTS: The
      preadministration of FDP markedly decreased the mortality of mice, almost
      reversed the impairment of learning and memory function, prevented the cells from
      delayed death in hippocampal neurons and blunted the rise in MAO-B activity after
      subacute CO poisoning of mice. CONCLUSION: FDP pretreatment markedly prevented
      mice from delayed encephalopathy after CO poisoning.

PMID- 11324469
TI  - Differentiation-inducing action of 10-hydroxycamptothecin on human hepatoma Hep
      G2 cells.
AB  - AIM: To study the mechanism of differentiation-inducing action of 10
      hydroxycamptothecin (HCPT) on human hepatoma Hep G2 cells. METHODS: The
      proliferating cell nuclear antigen (PCNA) expression was studied by
      immunocytochemical staining method. The cell cycle distribution and the wild-type
      protein p53 expression were measured by flow cytometry. Telomerase activity was
      assayed with telomeric repeat amplification protocol (TRAP). RESULTS: After
      treatment with HCPT at differentiation-inducing concentrations 5-20 micrograms.L
      1 for 6 d, Hep G2 cells were mainly arrested at G2/M phase and the PCNA
      expression rate was lower than that of control cells. When Hep G2 cells grew in a
      medium containing HCPT 5 micrograms.L-1 for 6 d, the p53 expression level
      markedly increased in comparison with the control cells. The telomerase activity
      did not change in Hep G2 cells treated with HCPT 5-20 micrograms.L-1 for 8 d.
      CONCLUSION: The differentiation-inducing effect of HCPT on Hep G2 cells is
      related with the cell cycle arrest at G2/M phase, down-regulation of PCNA and up
      regulation of wild-type protein p53.

PMID- 11324470
TI  - Effect of nitric oxide on electric and mechanical activities of gastric antral
      circular muscles in guinea pigs.
AB  - AIM: To study the effect of exogenous nitric oxide (NO) on electric and
      mechanical activities of gastric antral circular muscle in guinea pigs in vitro.
      METHODS: Mechanical and electric activities of gastric antral circular muscle in
      guinea pigs were recorded simultaneously. RESULTS: Sodium nitroprusside (SNP, 0.5
      mumol.L-1), an NO donor, inhibited the frequency and amplitude of fast wave and
      spontaneous contraction of the strips (P < 0.01). SNP-induced inhibition was not
      blocked by tetrodotoxin, atropine, phentolamine, and propranolol (P > 0.05), but
      diminished by methylene blue (P < 0.01) and oxyhemoglobin (P < 0.01). CONCLUSION:
      Exogenous NO inhibits gastric antral myoelectric and mechanical activities in
      guinea pigs. The inhibitions are produced by NO acting on extracellular membrane
      and enhancing the level of cGMP.

PMID- 11324471
TI  - Blocking effects of heteroclitin D and gomisin J on L-type calcium channels in
      ventricular cells of guinea pig.
AB  - AIM: To study the effects of heteroclitin D (HD) and gomisin J (GJ), two lignans
      from Kadsura medicinal plants, on L-type calcium channels in ventricular cells of
      guinea pig. METHODS: The calcium currents were measured by whole-cell patch-clamp
      recording technique. RESULTS: HD 1 and 10 mumol/L decreased the L-type calcium
      current from (770 +/- 155) to (482 +/- 104) and (384 +/- 85) pA, respectively. GJ
      10 mumol/L inhibited calcium current from (822 +/- 169) to (436 +/- 143) pA.
      Neither HD nor GJ affected the steady-state activation curve. But they had impact
      on steady-state inactivation curve. HD 10 mumol/L changed the half inactivation
      voltage (V0.5) from -22.7 to -40.9 mV, and slope factor (kappa) from 10.2 to 20.6
      (n = 4 cells from 3 guinea pigs, P < 0.05). GJ 10 mumol/L changed the V0.5 from 
      17.7 to -33.3 mV, and kappa from 15.9 to 27.8 (n = 5 cells from 3 guinea pigs, P
      < 0.05). CONCLUSION: HD and GJ inhibited L-type calcium channels.

PMID- 11324472
TI  - Cholecystokinin analog JMV-180-induced intracellular calcium oscillations are
      mediated by inositol 1,4,5-trisphosphate in rat pancreatic acini.
AB  - AIM: To investigate whether inositol 1,4,5-trisphosphate (IP3) is involved in
      secretory response of pancreatic acini to cholecystokinin (CCK) analog Boc-Tyr
      (SO3H)-Nle-Gly-Trp-Nle-Asp-2-phenylethylester.2NH3 (JMV-180). METHODS: Dynamics
      of cytosolic Ca2+ concentration, [Ca2+]c, was recorded by ratiometry of Fura-2 in
      pancreatic acini. RESULTS: In perfused preparations of isolated rat pancreatic
      acinar cells, 2-aminoethoxydiphenylborate (2APB), a new membrane permeant
      inhibitory modulator of IP3-mediated calcium release from internal stores,
      inhibited JMV-180-induced [Ca2+]c spikes, and 2APB at 100 mumol.L-1 resulted in
      an immediate, complete inhibition of the spikes. CONCLUSION: Recurrent [Ca2+]c
      spikes induced by continuous stimulation with JMV-180 are initiated via IP3
      mediated Ca2+ release from internal Ca2+ stores.

PMID- 11324473
TI  - Effects of angiotensin-converting enzyme and angiotensin II on hypoxia-induced
      proliferation of cultured intra-pulmonary artery smooth muscle cells.
AB  - AIM: To investigate whether local angiotensin-converting enzyme (ACE) and
      endogenous angiotensin II (ANG II) are involved directly in the proliferation of
      intra-pulmonary artery smooth muscle cells (PASMC) induced by hypoxia. METHODS:
      Smooth muscle cells isolated from rabbit intra-pulmonary artery (300-400 microns
      diameter) were cultured and used in the 3-8 passages. [3H]Thymidine incorporation
      and cell counts were used to measure PASMC proliferation. RESULTS: Exposure of
      PASMC to hypoxia for 24 h resulted in an increase in the [3H]thymidine
      incorporation and cell number by 166.6% and 52.0% as compared with normoxia (P <
      0.01). Treatment with either captopril or losartan markedly inhibited the
      increase, compared with the control, [3H]thymidine incorporation was inhibited by
      51.3% (P < 0.01) and 49.8% (P < 0.01) and cell number was inhibited by 22.2% (P <
      0.01) and 17.9% (P < 0.01), respectively, while PD-123319 showed no significant
      effect. CONCLUSION: Local overexpression of PASMC ACE and ANG II play an
      important role in the proliferation of PASMC induced by hypoxia.

PMID- 11324474
TI  - [Study on the enantiomeric separation of adrenalines by capillary zone
      electrophoresis].
AB  - Capillary zone electrophoresis (CZE) has been used for the enantiomeric
      separation of the racemic isoprenaline, noradrenaline and adrenaline with bare
      fused silica capillary and employing beta-cyclodextrin(beta-CD) and beta
      cyclodextrin derivatives as the chiral selectors. Both the complexion and
      enantiomeric resolution were influenced by the temperature, beta-CD type, CD
      concentration and pH of background electrolyte (BGE). The effects of the BGE
      types and concentrations on the enantiomeric separation were also investigated.
      The results showed that 2,6-di-O-carboxymethyl-beta-cyclodextrin (CM-beta-CD) has
      stronger recognition than that of beta-CD for the chiral separation of the basic
      drugs under study. The CD concentrations and pH of BGE have strong influence on
      the efficiency of chiral separation. The adsorption of the basic compound on the
      surface of bare fused silica capillary is a disadvantage to the chiral separation
      while the use of beta-CD as the chiral selector and the addition of an
      amphiphile, such as tetraethylammonium bromide (TEA+) or tetrabutylammonium
      bromide (TBA+) to the BGE could improve the resolution of the enantiomers due to
      the reduction of the adsorption of the basic compound on the silica surface by
      the strong electrostatic force between the positively charged amphiphile and the
      silica surface. It was also found that as CM-beta-CD was used as the chiral
      selector there was no influence on the chiral separation of the basic compound
      whether the amphiphile was added to BGE or not. Lower temperature was favorable
      to improve the efficiency of the chiral separation. CM-beta-CD gave a baseline
      enantiomeric separation for isoprenaline, while beta-CD, under the same
      experimental conditions, gave an incomplete chiral separation. Both CM-beta-CD
      and beta-CD could not give enantiomeric resolution for noradrenaline and
      adrenaline.

PMID- 11324475
TI  - [The advances of the methods for preparation of the coated capillary used in
      capillary electrophoresis].
AB  - The most successful method for controlling the adsorption of proteins onto the
      capillary inner surface in CE is the modification of the capillary surface with
      coating. The advances of the method for preparation of the coated capillaries are
      systematically reviewed with 39 references in the present paper.

PMID- 11324476
TI  - [New development of hydrophobic interaction chromatography and its applications
      in biochemical research].
AB  - This review is mainly concerned with the recent developments in (i) the retention
      mechanism of biopolymers in hydrophobic interaction chromatography (HIC); (ii)
      the synthesis of HIC packings, such as, the packings based on the inorganic and
      organic matrices, non-porous packings and porous membranes; (iii) the
      applications of HIC in both purifications of biopolymers and biochemical
      research, such as, renaturation and refolding of some denatured proteins, the
      change in molecular conformation of biopolymers. The review includes 62
      references and a table.

PMID- 11324477
TI  - [Lecture of principles and applications of capillary electrophoresis (VI)
      Applications of CE in DNA analysis, carbohydrate analysis and capillary ion
      analysis].
AB  - A review with 87 references on the application and new development of CE in DNA
      analysis, carbohydrate analysis and capillary ion analysis is presented. The DNA
      analysis included determinations of nucleotide, nucleoside and bases by CZE and
      MECC. It also includes dsDNA, PCR products analysis, purity control of
      oligonucleotide and DNA sequencing by CGE. Sometimes LIF detector needs to be
      introduced into DNA analysis. The carbohydrate analysis includes the methods for
      chemical derivatization and direct determination of carbohydrates by different CE
      modes. The capillary ion analysis includes the principle and determination of
      anions and cations.

PMID- 11324478
TI  - [The preparation of chiral column of cellulose triacetate coated on small pore
      silica gel and the separation of enantiomers].
AB  - The cellulose triacetate (CTA) prepared by heterogeneous acetylation and coated
      on small pore 3-aminopropyl silica gel (10 nm) was used as chiral stationary
      phase for HPLC (OA column). The racemes of three drugs, two fulvenes and one
      dazine, were separated on this column. Among these racemes, timolol maleas was
      separated using 1.0 mol/L NaClO4:95% ethanol = 10:90 as mobile phase. Without
      NaClO4 in mobile phase, the resolution of timolol maleas can not occur. Ethanols
      of 95%-98% were used as mobile phase for other racemes. The influence of the
      content of water in mobile phase on the chiral separation of praziquentelum, the
      retention time and separation factor (alpha) were reduced with the increase of
      water content in mobile phase. When the content of water in the mobile phase was
      13%, praziquentelum could not be separated. It was found that in the case of
      samples No. 1 and No. 2, when the substituents R1 and R2 or R'1 and R'2 of
      fulvenes are 4-methoxybenzoyl and 4-methoxyphenyl, the chiral separations of
      fulvenes can be obtained. For sample No. 4 when R1 and R2 of fulvenes are 2
      methylbenzoyl and 2-methylphenyl or in the case of No. 5, when R1 and R2 are 5
      bromo-2-furoyl and 5-bromo-2-furan, the chiral separations of fulvenes can not be
      achieved. For sample No. 6 and No. 7, when R'1 are 4-chlorobenzoyl and benzoyl or
      R'2 are 4-chlorophenyl and phenyl, the chiral separation also can not be
      achieved. The column performance and separation factor were not obviously reduced
      after used for four months.

PMID- 11324479
TI  - [Determination of vincristini sulfas in tumor cells by high performance liquid
      chromatography].
AB  - Vincristini sulfas (VCR) is an important common antitumor drug. The resistance to
      anticancer drug is the main cause of the chemotherapy failure. To screen the
      drugs which can reverse VCR resistance for VCR resistant cell strain, an
      analytical method has been established for the determination of VCR concentration
      in tumor cells using high performance liquid chromatography (HPLC). The stainless
      steel column was 25 cm x 4.6 mm i.d. packed with totally porous, spherical silica
      particles (5 microns). A solution of methanol and 0.02 mol/L dipotassium hydrogen
      phosphate (80:20, V/V) adjusted to pH 6.6 with H3PO4 was employed as the mobile
      phase. The flow rate was 1 mL/min. Chromatography was performed with ultraviolet
      detector at 267 nm. The method is simple, rapid and selective. Linear calibration
      curve for VCR was measured within the range of 10 to 200 mg/L with correlation
      coefficient of 0.999 8. The lowest detection limit was 4 mg/L tumor cells
      extract. The HPLC method described is suitable for clinical monitoring and
      pharmacokinetic study of VGR.

PMID- 11324480
TI  - [Rapid determination of essential fatty acids of edible oils by conversion to
      their hydroxamic acids].
AB  - A simple and rapid HPLC method for the determination of essential fatty acids of
      edible oils was established. Oil samples were converted to their hydroxamic acids
      in a single step and analyzed without prior separation and purification. The
      chromatographic conditions were: Shim-pack CLC ODS, 5 microns, 150 mm x 6.0 mm
      i.d. column, 40 degrees C; MeOH: 0.02 mol/L NaH2PO4(pH 3.0) (81:19, V/V) as
      eluent and UV-213 nm detector. The linear range was 0.05-0.6 g/L, recovery was
      96.93% and RSD was 1.80%(n = 4). The relative standard deviations for intra-day
      and inter-day assays were 1.24% and 1.62% respectively (n = 6). For 18:3, 18:2,
      18:1, the difference between the derivatization yields from triglycerides and
      their methyl esters was almost one fold. That was confirmed by our recovery and
      determination results. The calibration curves for the oil samples should not be
      obtained from the derivatization of their methyl ester standards.

PMID- 11324481
TI  - [Chiral HPLC determination of conversion and enantiomeric excess of enzyme
      catalyzed stereoselective esterification of racemic ibuprofen].
AB  - In the study of enzyme catalyzed kinetic resolution of racemates, it is
      imperative to assay how the optical yield varies with chemical conversion. In
      this paper, a method using one-time injection to determine enantiomeric excess
      and conversion of the stereoselective esterification of racemic ibuprofen with n
      butanol catalyzed by lipase was developed with a commercially available HPLC CSP
      column Regis(S, S) Whelk-01. In the linear range of detector, all peak areas of
      products and substrates are proportional to their concentrations. Because the
      total mole concentration remains unchanged (equal to the initial value of
      ibuprofen) in the reaction process, the conversion could be calculated from the
      peak areas, provided the ratio of response factors was known. The calibration
      curves of two ibuprofen enantiomers with racemic ibuprofen as external standard
      were overlapped, indicating fiR = fiS. By investigating the variation of peak
      areas of products and substrates against conversion (determined by external
      standard), the ratio of peak area-concentration response factor of ibuprofen
      butyl ester to that of unreacted ibuprofen was determined to be 1 through linear
      regressions, from which the conversion could be directly determined by the self
      normalization of the peak areas. With a mobile phase of
      IPA/hexane/HAc/triethylamine (15/85/0.2/0.05, V/V, flow rate 0.4 mL/min), the
      resolution of ibuprofen enantiomers was sufficient for precise enantiomeric
      purity determination.

PMID- 11324482
TI  - [Simultaneous analysis of organic acids and inorganic anions in alcoholic drink
      (dongjiu) by ion chromatography].
AB  - An ion chromatographic method for the simultaneous analysis of organic acids and
      inorganic anions in Dongjiu (alcoholic drink) was developed. An anion exchange
      column Shim-pack IC-A1(100 mm x 4.6 mm) was used. In non-suppressed anion
      exchange chromatography, potassium hydrogen phthalate (KHPh) is used as eluent
      most widely. However, there are several problems in this eluent for the analysis
      of Dongjiu (alcoholic drink) sample, such as the influence of a negative peak to
      the determination of acetic acid, ascorbic acid and lactic acid, the non
      resolution of ascorbic acid, and lactic acid, and part overlapping of the peak of
      acetic acid with water peak. In order to solve these problems, a mixed eluent of
      0.50 mmol/L KHPh and 0.25 mmol/L phthalic acid(H2Ph) was used in this work. The
      main organic acids and inorganic anions in Dongjiu were separated without
      interference peaks. The detection limits obtained by using the mixed eluent were
      0.05-0.13 mg/L, several times lower than those obtained by using single KHPh
      eluent. This method, being without pretreatment, is simple to operate.

PMID- 11324483
TI  - [Determination of anions in natural water with low pressure ion chromatography].
AB  - An application of low pressure ion chromatography to the analysis of natural
      water is described. Cl-, NO3- and SO4(2-) in the local tap water, lake, river and
      rain waters were separated and quantified. The limits of detection for Cl-, NO3-
      and SO4(2-) were 0.0136, 0.204, and 0.161 mg/L, respectively, and the recoveries
      were between 90% and 104%. The optimum condition is 1.44 mmol/L of Na2CO3 in
      eluent at a flow rate of 1.2 mL/min. The conductivity detector was used at 1.4 mu
      omega-1 and the sample volume injected was 20 microL. Similar chromatographic
      condition is also suitable for determination of NO2- and SO3(2-) in water
      samples. Furthermore, the limitations of the eluent composition used is also
      discussed.

PMID- 11324484
TI  - [Micellar paper chromatographic separation of structural isomers of
      diphenylmethyl alcohols and their chromatographic behaviour].
AB  - Structural isomers of nine diphenylmethyl alcohols (DPMA) have been separated by
      paper chromatography with sodium dodecylsulfate(SDS) micellar pure water solution
      as mobile phase and their Ri data are measured in different concentrations of SDS
      surfactant aqueous solution with no other additives. However, the curves of Cm vs
      Ri/(1 - Ri) deviate considerably from the Armstrong's ideal curve and are
      sawtoothed. The reason is that there is a big stereoscopic effect of DPMA
      compounds. The partly antibinding behaviour of the sawtoothed shapes comes from
      the effect which decides that DPMA cannot enter micellar core, otherwise the
      entropy of micellar system would be reduced or micellar will be broken, although
      both of them have hydrophobic property. One of the Armstrong's equations is shown
      as: [formula: see text] In this case, Km in the equation is negative. The above
      equation comes from a special condition in which there is only one type of
      micelle, however, there are several kinds of micelles for real system which is in
      dynamic equilibrium. Armstrong gave the correct pseudophase retention equation
      for 2:1 complexes [formula: see text] The DPMAs' chromatographic behaviour is the
      synthetic results of K1 and K2, both of which can be more than or less than zero,
      respectively or simultaneously, so the curves show sawtoothed shapes. The
      suitability of the relationship between the solutes' molecular structures and the
      micellar shapes and sizes is the main driving force of chromatographic
      separation.

PMID- 11324485
TI  - [Determination of two components in chloramphenicol and hydrocortisone ear drops
      by high performance liquid chromatography].
AB  - Chloramphenicol and hydrocortisone ear drops are possessed of anti-inflammatory
      and antiallergic functions. It can be used effectively in the treatment of
      tympanitis. It is composed of chloramphenicol and hydrocortisone. In this paper,
      we report a reversed phase HPLC method for the determination of chloramphenicol
      and hydrocortisone in the drops. The operatings conditions were YWG-C18 column (5
      microns, 5 mm x 150 mm) at 30 degrees C, mobile phase of methanol-water (60:40,
      V/V) and UV detector at 244 nm. Prednisone acetate was selected as the internal
      standard. The linear relationship of calibration curves was good in the range of
      40-200 and 8-40 mg/L for chloramphenicol and hydrocortisone, respectively (r =
      0.9999). The average recovery and RSD of chloramphenicol and hydrocortisone were
      99.91%, 0.86% and 99.58%, 1.34% (n = 6) respectively. The total time for
      separation and determination was within 9 min. The method was simple, sensitive,
      rapid and accurate.

PMID- 11324486
TI  - [Determination of etoposide (VP16) in human serum by high performance liquid
      chromatography].
AB  - A rapid high performance liquid chromatographic method for the determination of
      etoposide (VP16) in human serum has been developed. The samples were added
      teniposide (VM26) as an internal standard, extracted with ethyl acetate and
      chromatographed on a reversed phase YWG-C18 column with UV detection at 254 nm.
      The mobile phase was CH3OH:H2O = 55:45 (V/V). The calibration curve was Y =
      0.0160 + 0.034X, r = 0.9991. It was reticlinear in the range between 0.5-50 mg/L.
      The detection limit was 0.1 mg/L. The average recovery was 95.0% +/- 0.2%. Intra
      day and inter-day RSD were 4.16% and 4.76% respectively. From the results it can
      be concluded that this method is reliable. This method has been used to determine
      VP16 concentration in patient serum. The data obtained showed that the
      sensitivity and selectivity of this method were adequate for drug monitoring in
      clinical research.

PMID- 11324487
TI  - [Quantitative determination of niphensamide by high performance liquid
      chromatography (HPLC)].
AB  - An HPLC method for the quantitative determination of Niphensamide in pesticide
      powder was developed. Column:Micropak-CH 5 microns (300 mm x 4.0 mm i.d.), mobile
      phase: CH3OH-H2O(1:1), detector: UV 254 nm, flow rate: 0.7 mL/min, column
      temperature: 25 degrees C. Under the above conditions, Niphensamide and other
      components were separated from each other. The method is simple, rapid, sensitive
      and accurate.

PMID- 11324488
TI  - [Determination of tranilast in human plasma by reversed-phase high performance
      liquid chromatography and its pharmacokinetics].
AB  - A simple and rapid method for the determination of tranilast in human plasma by
      RP-HPLC is described. The analytical column was packed with YWG-C18. The mobile
      phase consisted of methanol-0.02 mol/L KH2PO4(60:40, V/V; pH 4.2), and detected
      by UV detector at a wavelength of 333 nm. The plasma sample was injected directly
      into the HPLC system after precipitation of the protein with methanol. The
      calibration curve was linear within the concentration range of 0.625-40 mg/L. The
      average recovery was 100.0% +/- 4.1%, and minimum detectable concentration was
      0.2 mg/L. By using this method, the pharmacokinetics of tranilast in the plasma
      of ten healthy volunteers after oral administration of 200 mg drug were studied.
      The plasma drug concentration-time curve of volunteers conforms to one
      compartment open model.

PMID- 11324489
TI  - [Determination of formic acid in urine by high performance capillary zone
      electrophoresis].
AB  - The amounts of formic acid in human urine has a direct bearing on the people's
      health. In this paper, high performance capillary zone electrophoresis was
      applied to separate formic acid of urine with a buffer system of 5 mmol/L
      phthalate-0.5 mmol/L hexadecyltrimethyl ammonium bromide (CTAB) and pH 6.
      Separations were performed in a 50 cm x 50 microns i.d. fused silica capillary
      (effective length 48.5 cm) at 25 degrees C. A negative potential of 30 kV was
      used for each experiment. Sample was introduced into the capillary by pressure at
      kPa for 10 s. Indirect UV detection was operated at 210 nm and reference
      wavelength at 380 nm for all experiments. Capillary was rinsed for 5 min with 0.1
      mol/L sodium hydroxide and buffer solution before each run. Urine was injected
      directly after filtered through 0.45 micron membrane. The results are
      satisfactory.

PMID- 11324490
TI  - [Determination of captopril in tablets by gas chromatography (GC)].
AB  - A GC method for determination of captopril in tablets was developed. The sample
      was esterified to improve its sensitivity. The conditions for determination were:
      2% OV-17 on 80-100 mesh Chromosorb W AW-DMCS packed in a 2 m x 3 mm i.d. column
      operated at 190 degrees C. Both FID detector and injector port at 220 degrees C.
      Octadecane was used as internal standard. The response was linear between 0.2 g/L
      and 1 g/L. This method is proved to be highly sensitive, good reproducible and
      satisfactory.

PMID- 11324491
TI  - [The analysis of fatty acid composition in syncytiotrophoblast plasma membranes
      of human placenta].
AB  - The fatty acids were determined in syncytiotrophoblast plasma membranes of the
      eighteen human placenta from the normal pregnant women. With the method of
      Landon, the fat was purified in syncytiotrophoblast plasma membranes, which was
      extracted from the placenta by using the procedure of Whitsett. The methylated
      fatty acids were separated with gas chromatography in which a glass column packed
      with DEGS was used. In comparing the retention time of the sample with the
      standards and referring to the results of GC/MS, thirteen peaks were identified
      and quantified. The area normalization method was used to determine the
      distribution, the compositions and contents of fatty acids in syncytiotrophoblast
      plasma membranes. It is shown that the amount of identified fatty acids attains
      74.1% of total peak area, in which the amount of saturated fatty acids was
      30.64%, and the unsaturated was 43.46%.

PMID- 11324492
TI  - [Determination of avermictin in avermictin tablet by high performance liquid
      chromatography].
AB  - A method for the separation and determination of avermictin in avermictin tablet
      by reversed-phase high performance liquid chromatography (RP-HPLC) was developed.
      Operating conditions were as follows: TSK-GEL C18 column, 250 mm x 4.6 mm i.d.,
      MeOH-H2O (75:25, V/V) mobile phase with a flow rate of 1.0 mL/min, and UV
      detection at 245 nm. The results showed that the active constituents avermictin
      B1a and B1b can by separated effectively. The relative standard deviations were
      2.56% and 1.31%, respectively (n = 6). The method is accurate, rapid and simple,
      and provides a scientific basis for industrial production and quality control of
      avermictin tablet.

PMID- 11324493
TI  - Effect of dl-3-n-butylphthalide on brain edema in rats subjected to focal
      cerebral ischemia.
AB  - The present study evaluated the effect of dl-3-n-butylphthalide(NBP), a novel
      brain protective agent, on brain edema in rats following focal ischemia. Edema
      was induced by occluding the right middle cerebral artery (MCAO), producing
      permanent focal ischemia in the right cerebral hemisphere, which developed
      ipsilateral brain edema reproducibly. Edema was assessed 24 h after MCA occlusion
      by determining the brain water content from wet and dry weight measurements, and
      the sodium, potassium concentrations with ion-selective electrodes. In this
      model, NBP at the dose of 80, 160 and 240 mg/kg p.o. 15 min after MCAO prevented
      from brain edema in a dose-dependent manner. A significant reduction of sodium
      content and an increase in potassium level were observed in all drug-treated
      groups. It showed that NBP strongly attenuated brain water entry, sodium
      accumulation and potassium loss. Nimodipine treatment (5 mg/kg s.c.) also reduced
      brain edema (P < 0.05). The results suggest that a strong anti-edema activity of
      NBP may play an important role to contribute to the treatment of ischemic damage.

PMID- 11324494
TI  - The polymorphisms of HLA-DR and TNF B loci in northern Chinese Han nationality
      and susceptibility to systemic lupus erythematosus.
AB  - With the aid of methods of polymerase chain reaction/sequence specific primers
      (PCR/SSP) and polymerase chain reaction-restriction fragment length polymorphism
      (PCR/RFLP), the allelic polymorphism of HLA-DR and TNFB loci and susceptibility
      to systemic lupus erythematosus (SLE) in northern Chinese Han nationality were
      studied. The genetic analysis of 51 patients with SLE and 106 healthy controls
      indicated that frequencies of DR2 and DR3 alleles were significantly increased in
      SLE patients (P < 0.05 and < 0.005, relative risks of 1.77 and 4.01
      respectively), which represent candidate susceptible genes or useful marker for
      SLE. The frequency of DR5 was found to decrease in SLE patients compared with
      control population (P < 0.025, relative risk = 0.38). It might be an antagonistic
      or protective allele or a marker for such allele. Analysis of 51 patients with
      SLE and 80 healthy control also revealed that the frequency of TNFB*2 allele was
      significantly increased (P < 0.05, RR = 1.70). Therefore TNFB*2 gene may also be
      a susceptibility gene or a marker gene for SLE in northern Chinese Han
      nationality. It was also investigated the association between HLA-DR, TNF B
      alleles and Patient plasmic SC5b-9 levels, auto-antibodies (anti-SSA, SSB, Sm,
      RNP, ds DNA and ANA) and SLE complications (SLE nephritis, SLE pneumonitis and
      SLE encephalopathy), no relationship was found.

PMID- 11324495
TI  - Seroprevalence of human herpesvirus-6 in healthy population in two provinces of
      north China.
AB  - BACKGROUND: Human herpesvirus-6 (HHV-6) infection is ubiquitous in selected
      population with seroprevalence of 60-80%. Little is known for that in China,
      except few sporadic studies. To understand prevalence of HHV-6 antibody in
      Chinese population, this seroepidemiological study was conducted. METHODS: Sera
      were collected from 430 healthy persons and donors living in North China, and
      tested for HHV-6 antibodies using IFA with HHV-6 GS strain passaged on HSB-2
      cells as antigen, and titer equal or higher than 1:10 was regarded as
      seropositive. RESULTS: Of the 430 serum samples tested, 297 (69.1%) were positive
      for HHV-6 IgG. Both seropositive rate and GMT in females were significantly
      higher than those in males, with X2 = 7.05, P < 0.01 and F = 7.23, P < 0.01,
      respectively. Statistically significant difference in prevalence of HHV-6
      antibody among various age groups was observed in both sexes, with X2 = 20.08 and
      20.28, P = 0.04, respectively, and young children had a higher titer than adults.
      But, no significant difference in prevalence was observed in blood donors between
      various age groups or both sexes. CONCLUSIONS: This study suggests that HHV-6
      infection with seropositive IgG is ubiquitous in North China, and its importance
      should be further studied.

PMID- 11324496
TI  - The clinical analysis of hypnotics and sedatives used in outpatient clinics in
      general hospital.
AB  - AIM: To statistic the usage of hypnotics and sedatives in outpatient and
      emergency clinics prescriptions in one day. METHOD: Check all prescriptions on
      April 29, 1987 and November 13, 1995 in order to know the quantity, kind and
      distribution of hypnotics and sedatives in different outpatient departments.
      RESULT: There were 1,319 prescriptions on April 29, 1987. Among them, hypnotics
      and sedatives were 122(9.24%); in comparing with 2,065 prescriptions on November
      13, 1995, hypnotics and sedatives were 141 (6.82%). Benzodiazepine used more than
      80% in all prescriptions. CONCLUSION: The possibility of long-term low-dosage
      using benzodiazepine is present. It must strengthen the control and education to
      avoid the drug-abuse.

PMID- 11324497
TI  - Long-term performance of steroid-eluting lead in dual chamber pacing.
AB  - The atrial pacing lead is believed having higher stimulation thresholds and long
      term complication rates than ventricular lead, this being one of the factors
      limiting the use of dual chamber pacing. A prospective study was undertaken to
      evaluate both atrial and ventricular bipolar tined steroid-eluting leads in long
      term dual chamber pacing. There are 81 pairs of leads (Medtronic Capsure SP) used
      in 81 patients. Bipolar atrial and ventricular stimulation thresholds were
      measured immediately post implantation and 1, 3, 6, 12, 18 and 24 months. All
      leads demonstrated low mean stimulation thresholds during the follow-up and more
      than 94% of leads could be paced chronically in the atrium and ventricle at 2.5
      volts. In conclusion, atrial and ventricular steroid-eluting leads gave excellent
      stimulation thresholds allowing low energy long-term dual chamber pacing.

PMID- 11324498
TI  - Magnetic resonance images of the hypothalamic-pituitary area in idiopathic growth
      deficiency.
AB  - In order to describe the magnetic resonance imaging (MRI) findings in
      hypothalamic-pituitary area and its clinical relevance in patients with
      idiopathic growth hormone deficiency (IGHD), the MR imagings of 26 patients with
      IGHD were analyzed. On MRI, 24 out of 26 cases (92.3%) showed apparent pituitary
      upper margin depression; 8 out of 26 cases (30.8%) showed definite pituitary
      stalk transection; 22 out of 26 cases (84.6%) showed absence of the normal
      posterior pituitary bright spot. The bright lipidlike signal on T1W1 images at
      the median eminence distal to the breaking point (so-called ectopic posterior
      lobe) was found in 4 out of 26 cases (15.4%). According to the MRI findings of
      the pituitary stalks, the 26 cases were divided into three groups; group A of 8
      cases (31%) characterized by the definite transaction of stalk; group B of 13
      cases (50%) defined by the possible stalk transection; and group C of 5 cases
      (19%) with no definite stalk transection. MRI findings were consistent with the
      clinical and endocrine tests. The stalk transection was statistically
      significantly difference in insulin test, L-dopa/p test, and height standard
      deviation score (P < 0.05). The MRI of hypothalamic-pituitary area may
      differentiate partial IGHD form stalk-transected, doubtful transection and
      without transection.

PMID- 11324499
TI  - Detection of human herpesvirus 6(HHV-6) DNA in salivary glands by the polymerase
      chain reaction.
AB  - To assess the presence of HHV-6-Specific DNA in human salivary glands, eighteen
      specimens of salivary gland tissue were investigated using the polymerase chain
      reaction. Eight of nine parotid glands, five of seven submandibular glands and
      one of two sublingual glands were found to have amplification of the HHV-6
      specific sequence. The findings suggest that salivary gland tissue is one of the
      potential sites for HHV-6 persistence following primary infection and that saliva
      is a vehicle for transmission of the virus.

PMID- 11324500
TI  - Pulmonary leiomyosarcoma.
AB  - Three cases of pulmonary leiomyosarcoma were presented. The characteristic
      clinical features were described with review of literature. In comparison with
      bronchogenic carcinoma, the leiomyosarcoma has some characteristics: 1) On chest
      X-ray, it usually appears as a sharply demarcated, even density round mass,
      growing rapidly within the lung, it unusually accompanies with hilar or
      mediastinal lymph node metastasis; 2) The preoperative cytological or
      pathological diagnosis is difficult either by sputum smear or by bronchoscopic
      biopsy or by fine needle percutaneous aspiration biopsy; 3) Pathological
      differential diagnosis of leiomyosarcoma of lung from anaplastic lung cancer is
      difficult. In conclusion, the primary pulmonary leiomyosarcoma is a rare
      malignant tumor, detecting the present illness seriously, paying attention to the
      chest X-ray films characterize, early surgical resection is the only way to get
      diagnosis and effective treatment method.

PMID- 11324501
TI  - Overexpression of p53, EGFR, c-erbB2 and c-erbB3 in endometrioid carcinoma of the
      ovary.
AB  - OBJECTIVES: To determine overexpression of p53, EGFR, c-erbB-2 and c-erbB-3 in
      endometrioid carcinoma of the ovary and to evaluate the prognostic significance
      of these results, especially, coexisting overexpression of p53 and one of the
      member of type I growth factor receptor family. METHODS: Overexpressions of the
      p53, EGFR, c-erbB-2 and c-erbB-3 protein were studied by immunohistochemistry in
      paraffin-embedded tumor tissue from 28 patients with endometrioid carcinoma of
      the ovary. RESULTS: 11 (39.3%), 13 (46.4%), and 14 (50.0%) were stained
      positively with p53, c-erbB-2 and c-erbB-3 monoclonal antibodies. 13 (46.4%) was
      stained positively with EGFR polyclonal antibody. There were no relationship
      between p53, EGFR, C-erbB-2, c-erbB-3 and histologic grade, lymph node
      metastasis. The percentage of tumors with over expression of p53, EGFR, C-erbB-2
      and c-erbB-3 was higher in those with stage II-III tumors compared with those
      with stage I, in patients with residual tumor after initial surgery compared with
      those without. A high survival rate was observed in patients without p53, EGFR, c
      erbB-2 and c-erbB-3 overexpression respectively than those with. A highest
      survival rate was observed in patients with both p53 and one of EGFR, c-erbB-2
      and c-erbB-3 negative compared with those both positive or either of both
      positive. CONCLUSION: Overexpression of p53, EGFR, c-erbB-2 and C-erbB-3 resulted
      in a poorer prognosis respectively. Overexpression of both p53 and one of the
      EGFR, c-erbB-2 and c-erbB-3 is a worse prognostic indicator in patients with
      endometrioid carcinoma of the ovary.

PMID- 11324502
TI  - p53 independent G1 arrest and apoptosis induced by adriamycin.
AB  - The biological activity of adriamycin was investigated in human breast carcinoma
      (HBC) cells, Adriamycin inhibited the growth of a number of HBC cell lines and
      induced G1 arrest followed by apoptosis. In MCF-7 cells that harbor wild-type
      p53, adriamycin-induced G1 arrest and apoptosis was accompanied by p53
      independent regulation of WAF1/CIP1 as well as bax mRNA levels. In MDA-MB-231
      cells which possess a mutant p53, adriamycin-induced G1 arrest and apoptosis was
      also associated with a concomitant up-regulation of WAF1/CIP1 mRNA while these
      cells did not express bax or bcl-2 messages. Thus, adriamycin induces G1 arrest
      and apoptosis via a unique pathway which appears to involve activation of
      downstream effectors of p53-independent manner.

PMID- 11324503
TI  - Suppression of malignant phenotype of a transformed mouse mammary epithelial cell
      line (11A1) by tumor suppressor gene RB.
AB  - A malignant transformed mammary epithelial cell line (11A1) was transfected with
      liposome encapsulated eukaryotic expression plasmid pCMV-neo-RB, yielding 4
      constant clones which have obvious phenotypic reversion changes, and named 11A1
      R1-R4 respectively. Further experiments showed that the 11A1-R1 behaved like
      normal epithelial cells in both morphological and biological characteristics,
      with decreased clonogenicity in solid argar medium as well as decreased
      tumorigenicity. Northern blot hybridization showed increased expression of RB
      gene and decreased expression of c-myc gene in 11A1-R1, 11A1-R2 cells compared to
      11A1 cells. This was an ideal phenotypic reversion model for epithelial
      transformed cell line and demonstrated that the RB gene can reexpress and
      suppress malignant phenotype in RB inactive cells.

PMID- 11324504
TI  - Radioimmunoimaging of human breast cancer xenografts in nude mice by using human
      anti-human breast cancer monoclonal antibodies.
AB  - In this study, the human breast cancer-bearing nude mice model has been
      established and the radioimmunoimaging was carried out by using human anti-human
      monoclonal antibodies. The results showed that the breast tumor-bearing nude mice
      received 131I-McAb-CM-1 had a clear image of the xenograft during 4 to 6 days
      after injection and at the same time T/NT all over 1.0. The highest T/NT reached
      7.1. It demonstrates that McAb-CM-1 can specially combine with breast cancer
      tissues and hopefully it could be used clinically to improve accurate rate of the
      early breast cancer diagnosis.

PMID- 11324505
TI  - Beta-turn new classification and its some features in proteins.
AB  - An inspection of the phi-psi angle distribution strongly suggests that protein
      folding is highly constrained. A number of researchers have even suggested that a
      relatively small set of discrete phi-psi regions might be sufficient to describe
      most protein conformation. The total of 541 tight turns from 101 non-identical
      proteins were extracted form Brookhaven DataBank. The dihedral values of tight
      turns were scattered into the seven regions on the Ramachandran plot. These seven
      regions were called A1, A2, B1, B2, B22, T1 and T2. A1 and A2 are the traditional
      alpha-helix regions, B1, B2 and B22 the beta-strand regions, T1 and T2 the beta
      turn regions. The A2 and T2 regions were not defined as "discrete" or single
      points but rather as one dimensional extended states. Based on the geometry of
      the two central residues of the tight turns, the new classification of beta-turn
      was defined. This classification of the majority of beta-turns fell into only six
      of the possible forty nine region combinations and were identifiable with the
      traditional nomenclature of Venkatachalam(1), but much simpler. The function of
      beta-turn in the conformation of proteins was studied. The hydrophobicity for
      different type turns was discussed. It shows that beta-turns have very strong
      hydrophilic property, so they are usually situated at the folding protein
      surface. The features of beta-turn and its amino acid distribution in this 541
      beta-turn group and different type beta-turn were given.

PMID- 11324506
TI  - The mutual benefit role of liver and pancreas in combined transplantation.
AB  - The present study observed the mutual benefit role of liver and pancreas in
      combined hepaticopancreatic transplantation in rats. The results indicated that
      pancreas, when transplanted with liver, could survive for a significant long time
      (13.4 +/- 1.01 days) than it transplanted alone (9.2 +/- 1.14 days) (P < 0.05, t
      test). The interstitial rejection was mild and its rejection grade was
      significantly different from that of pancreas transplanted alone (P < 0.05, X2
      test). The liver, when transplanted with pancreas, regenerated with strong
      competence and contact structure morphologically compared with liver transplanted
      alone. We think that pancreas could be immunologically protected against
      rejection and liver can be nutritionalized by pancreas in combined liver and
      pancreas transplantation.

PMID- 11324507
TI  - Changes in airway space following mandibular setback using sagittal split
      osteotomy and rigid internal fixation.
AB  - The changes in airway space following mandibular setback using sagittal split
      osteotomy and rigid internal fixation were studied in 28 Japanese patients with
      mandibular prognathism. The correlation between the amount of mandibular setback
      and airway space changes, as well as the correlation between the amount of airway
      space changes and relapse of pognion point during the following-up period were
      also studied. Lateral cephalometric radiographs were taken immediately before and
      shortly after surgery as well as 5 to 12 months postoperation. The cephalometric
      evaluations of airway space width and area were based on stable craniofacial
      landmarks. The mean setback of mandible was 8.3 mm in the right side, and 8.2 mm
      in the left side. The mean amount of relapse of pogonion point during the
      following-up period was 0.52 mm horizontally, and 0.92 mm vertically. A
      significant decrease in airway space width and area, especially in the lower part
      of airway space was found following mandibular setback shortly after surgery.
      Although there was some increase both in airway space width and area during the
      following-up period, they did not increase to their original values. This
      suggests that the narrowing of airway space following mandibular setback using
      sagittal split osteotomy can be permanent. No significant correlation was found
      between the amount of mandibular setback and airway space changes. Since the
      relapse of pogonion point during the following-up period was too small, there is
      no significant correlation between it and the amount of airway space changes.

PMID- 11324508
TI  - [Frequency dependence of somatostatin and calcitonin gene related peptide release
      induced by electroacupuncture in rat spinal cord].
AB  - Radioimmunoassay (RIA) was used to determine the changes of the immunoreactivity
      (ir) of somatostatin (SOM) and calcitonin gene-related peptide (CGRP) in the
      spinal perfusate of rat induced by electroacupuncture (EA) of different
      frequencies. The frequency of EA was chosen to be 2, 15 and 100 Hz and the spinal
      perfusate was collected in three periods of 30 min before, during and after EA.
      The results indicate: (1) low frequency EA (2 Hz) increased the spinal SOM-ir
      level by 39% (P < 0.05) but decreased that of CGRP-ir by 47% (P < 0.05); (2)
      conversely, 15 Hz EA decreased spinal fluid SOM-ir level by 37% (P < 0.05) but
      increased that of CGRP-ir by 92% (P < 0.05); (3) 100 Hz EA behaved like 15 Hz in
      inhibiting SOM-ir level (P < 0.01), but without effect on CGRP-ir. The above
      results show that specific frequency is required for peripheral electrical
      stimulation to activate or suppress the release of spinal neuropeptides SOM and
      CGRP, a fact that may have clinical implications.

PMID- 11324509
TI  - [Effects of stimulation at different areas of nucleus raphe dorsalis on
      genioglossus and diaphragm activities].
AB  - Effects of electrical and chemical stimulation of the dorsal and ventral areas of
      the nucleus raphe dorsalis (dNRD and vNRD) on genioglossus and diaphragm
      activities were observed in 48 urethane-anaesthetized and vagotomized rabbits.
      (1) Long train electrical stimulation at the dNRD facilitated genioglossus and
      diaphragm activities. (2) Long train electrical stimulation delivered to the vNRD
      excited genioglossus activity but inhibited diaphragm activity. (3) Effects of
      microinjection of glutamate at the dNRD and vNRD were similar to the effects of
      electrical stimulation. The above results suggest that excitation of nucleus
      raphe dorsalis (NRD) increases genioglossus activity and reduces upper airway
      resistance. The dNRD and vNRD play different roles in modulating diaphragm
      activity.

PMID- 11324510
TI  - Prolactin inhibition of FSH-induced tissue type plasminogen activator expression
      in cultured rat granulosa cells.
AB  - This study was designed to investigate whether prolactin (PRL) affects
      coordinated regulation of tissue plasminogen activator (tPA) and plasminogen
      activator inhibitor type-I(PAI-I) gene expression in rat granulosa cells in
      vitro. Several methods, such as SDS-PAGE, immunoblot etc. were used to detect the
      effect of PRL on tPA and PAI-I gene expression. The results demonstrated: (1) PRL
      increases PAI-I mRNA production in cultured granulosa cells. Inclusion of
      follicle stimulating hormone (FSH) with PRL has a synergistic effect on the
      increase of PAI-I mRNA levels. After 48 h culture in the presence of FSH with
      PRL, a 7.8-fold increase in PAI-I mRNA levels is observed as compared with PRL
      alone. The synergistic increase in PAI-I mRNA levels occurs in a dose- and time
      dependent manner; (2) the increase in PAI-I mRNA synthesis in the cells by PRL
      alone, or PRL in combination with FSH, is well correlated with the changes of PAI
      I activity levels in the conditioned media; (3) PRL in culture also decreases FSH
      induced tPA activity level in a dose-dependent fashion. The decrease in FSH
      induced tPA activity level by PRL is correlated with an increase in the amount of
      PA-PAI-I complexes in the conditioned media. This suggests that the decline of
      tPA activity is related to neutralization of tPA by the increased PAI-I activity
      in the media.

PMID- 11324512
TI  - [Effect of cGMP on calcium-activated potassium channels in primary cultured
      porcine coronary artery smooth muscle cells].
AB  - Guanosine 3',5'-cyclic monophosphate (cGMP) is capable of relaxing vascular
      smooth muscle through activating calcium-activated potassium channels (KCa
      channel) in the vascular smooth muscle cell membrane. But regarding the mechanism
      it is still under debate. In the present work the mechanism of the effect of cGMP
      on KCa channel in primary cultured porcine coronary artery smooth muscle cells
      using patch clamp technique was investigated. Experimental results showed that
      (1) different concentrations of 8-bromo-cGMP (0.25 mmol/L, 0.50 mmol/L, 1.00
      mmol/L), serving as a membrane permeable analogue, could activate KCa channels,
      and (2) 1.00 mmol/L 8-bromo-cGMP could not activate such kind of channels in
      inside-out patch under the same condition. These results suggested that the
      activating effect of cGMP on KCa channels was indirect, being mediated by some
      intracellular process.

PMID- 11324511
TI  - [Effects of receptor-mediated endocytosis on macrophage membrane potential,
      cytosolic pH and lysosomal pH].
AB  - The effects of Con A, WGA, Zymosan A on membrane potential, cytosolic pH and
      lysosomal pH of cultured mouse macrophages were measured with fluorescence
      method. The results showed all the three kinds of ligands caused macrophage
      membrane potential hyperpolarization, cytosolic acidification and lysosomal
      alkalization, but reached their stabilized conditions at different times. The
      acidification of cytosl might inhibit further endocytosis. Alkalization of
      lysosomes was a basic factor for exocytosis of lysosomal contents. These receptor
      mediated induced changes reflected cellular self-regulation and self-protection.

PMID- 11324513
TI  - [Inhibitory effects of clonidine on GABA-activated currents in rat DRG neurons].
AB  - Whole-cell patch-clamp recordings were performed on neurons from freshly isolated
      rat dorsal root ganglion (DRG) to investigate modulatory effects of clonidine, an
      alpha 2-adrenoceptor agonist, on GABA-activated currents. In the majority of the
      neurons examined (72/75), GABA (10(-6)-10(-3) mol/L) induced a concentration
      dependent inward current, which could be blocked by bicuculine (10(-4)-10(-5)
      mol/L). In 51 out of 72 cells, pretreatment with different dosages of clonidine
      (10(-8)-10(-4) mol/L) decreased the GABA (10(-4) mol/L)-activated current by
      8.5%, 19.0%, 33.4%, 44.4% and 40.3%, respectively, while clonidine itself only
      induced a slight inward current in a few cells (12/72). The inhibitory action of
      clonidine blockable by yohimbine (10(-4) mol/L) was voltage-independent and did
      not change the membrane conductance during the activation of GABAA receptor.
      Unlike NA, (-)-isoproternol (10(-4)-10(-5) mol/L) exerted no effect on GABA
      activated currents. Intracellular application of H-7 (10(-4) mol/L) via
      micropipette resulted in a significant blockade of clonidine inhibition (19/20)
      except one cell showing only a slight inhibition (11.2%). The results suggest
      that the inhibitory effect of clonidine on GABA-activated currents in DRG neurons
      might involve phosphorylation of GABAA receptor following activation of alpha 2
      adrenoceptor through a mechanism of intracellular transduction.

PMID- 11324514
TI  - [A new way for neural transplantation: the grafted central neurons migration from
      the subarachnoid space into the spinal cord and cerebral cortex].
AB  - In the studies of neural transplantation, Chen and his colleagues observed that
      the grafted central neurons could migrate from the subarachnoid space into the
      spinal cord and cerebral cortex. This finding promises an attractive possibility
      that a lot of neurons might be introduced into a long distance of the spinal cord
      and the extensive superficial layer of the brain which has suffered neuronal loss
      and thus might reinnervate a wide range of denervated area. Female rats were used
      in the study. Neural tissues or cell suspension containing fetal monoaminergic or
      arginine vasopressin (AVP) neurons were implanted into the subarachnoid space of
      the transected spinal cord or the normal brain and spinal cord. The rats were
      treated in different ways: some were grafted and the spinal cord was cut at the
      same time; grafted one month later or before the spinal cord was cut; grafted but
      the brain and spinal cord remained intact. Immunohistochemical method was used to
      monitor the grafted neurons after these rats survived for one or nine months. The
      results showed that there were a few to hundreds of 5-HT, TH or AVP
      immunoreactive neurons and fibers found in the spinal cord or cerebral cortex
      near the grafted region. These neurons grew well and displayed their capacity of
      adaptability and long-time survival in the host CNS. No neurons, however, were
      found in the subarachnoid space of the grafted rats which had survived for
      another month or longer. On the other side, grafted with tissue block, it was
      found that transplants left in the grafted region grew as a "nodule" attaching to
      the surface of the spinal cord. The "nodule" was also found occasionally when the
      cell suspension was centered heavily at one region of the subarachnoid space. In
      both cases, the pia mater between them disappeared. Immunoreactive neurons were
      found in the "nodule" and neighboring spinal cord, some fibers from the neurons
      in the "nodule" extended into the spinal cord. It is supposed that a part of
      cells in the suspension died after grafted in the subarachnoid space and released
      hydrolases which injured the near pia mater by hydrolysis. As a result, some
      neurons in the suspension had a chance to migrate into the spinal cord and
      cerebral cortex. After the transplant in the subarachnoid space was gradually
      cleaned out, the enzymatic hydrolysis to the pia mater became weaker and finally
      stopped, the lesioned pia mater was gradually repaired. If the transplant was not
      cleared timely, the pia mater could not withstand the persistent hydrolysis and
      collapsed finally, leading the transplant to be fused with the host CNS.

PMID- 11324515
TI  - [Modulation of bradykinin on ATP-activated currents in isolated rat DRG neurons].
AB  - Modulation of bradykinin (BK) on ATP-activated membrane currents in the isolated
      rat dorsal root ganglion (DRG) neurons was investigated using whole-cell patch
      clamp technique. In 56 neurons examined, BK (10(-6)-10(-4) mol/L)-induced
      responses were as follows: (1) inward current (40/56); (2) outward current
      (7/56); (3) no responses (9/56). In the majority of the neurons examined, ATP
      (10(-6)-10(-3) mol/L) activated a concentration-dependent inward current with
      obvious desensitization. ATP-activated current was potentiated markedly by
      preapplication of BK. The enhancement of BK was dependent on the concentration of
      BK and ATP. It was found that BK potentiated the peak value of ATP-activated
      currents predominately while the steady state value was not affected obviously.
      The onset of BK potentiation of ATP-activated currents needed preincubation of BK
      at least for 30 s and the time of the enhancement lasted over 20 min. The results
      suggest that BK may play a role in the facilitation of the excitatory effect of
      ATP on primary sensory neurons.

PMID- 11324516
TI  - [Effect of intrathecal injection of dopamine receptor agonists/antagonists on
      pain and acupuncture analgesia in rats].
AB  - Some selective dopamine receptor agonists and antagonists were tested on rat tail
      flick model to investigate the role of D1 and D2 dopamine receptor in pain and
      acupuncture analgesia (AA). It was found that intrathecal administration (i.t.)
      of D2 receptor agonist LY171555 or D1/D2 receptor agonist apomorphine increased
      pain threshold and had a potentiating effect on AA. In contrast, D1 receptor
      agonist SKF38393 had no effect. It D1 receptor antagonist SCH23390 or D2 receptor
      antagonist sulpiride attenuated the effect of AA. The results suggest that D2
      receptor is involved in pain modulation and activation of D2 receptor and
      enhances AA in the spinal cord, while such effect is absent in D1 receptor and
      inactivation of D1 receptor attenuates AA.

PMID- 11324517
TI  - [Monosynaptic transmission between mesodiencephalic neurons and motoneurons
      innervating extraocular inferior oblique muscle in cats].
AB  - The present study was performed to define the synaptic connection of neurons
      located within the dorsal mesodiencephalic junction with motoneurons innervating
      extraocular inferior oblique muscle (IOMN) using electrophysiologic, especially
      spike-triggered averaging technique in cats. In response to electric shocks
      applied to the medial part of Forel's field H (FFH) located in the
      mesodiencephalic junction, excitatory monosynaptic field potentials were observed
      in the IOMN pool. Moreover, while the spontaneous discharges of FFH neurons were
      used to trigger the activity of IOMN pool from which the induced potential
      changes were averaged, an excitatory monosynaptic field potential was also
      obtained. These results indicate that the mesodiencephalic neurons connect with
      and activate the IOMNs monosynaptically, and drive vertical eye movements via
      such a way.

PMID- 11324518
TI  - [Inhibitory effects of nitric oxide on glutamate-induced neuronal activity of CA1
      area in rat hippocampal slices].
AB  - Using extracellular recording technique, the effects of L-arginine (L-arg), SIN-1
      and N-nitro-L-arginine (L-NNA) on glutamate-induced discharge of neurons in CA1
      area of hippocampal slices were examined to define the role of L-arg:NO pathway
      in glutamate-induced discharge of hippocampal neurons and its possible underlying
      mechanism. The results obtained are as follows. (1) In response to the
      application of glutamate (0.5 mmol/L) into the superfusate for 1 min, the
      discharge rate of 12 neurons was increased markedly in an epileptiform pattern.
      (2) The increased discharge induced by glutamate (0.5 mmol/L) in 10 neurons was
      suppressed significantly by application of L-arg (10 mmol/L) into the superfusate
      for 2 min. (3) The glutamate-induced increase of discharge in 12 neurons was
      decreased markedly by superfusing the brain slice with NO donor SIN-1 (5 mmol/L)
      for 1 min. (4) As the discharge rate of 12 neurons was increased by pretreatment
      with glutamate (0.5 mmol/L), application of L-NNA (0.15 mmol/L) into superfusate
      for 2 min might further augment the discharge intensively and in some case
      eventually led to abrupt suppression of the discharge. Taken together, it is
      likely that glutamate binding with NMDA receptors in hippocampal neurons not only
      induces an increase in discharge, but also activates the L-arg: NO pathway to
      generate NO responsible for neuroprotection via negative feedback mechanisms.

PMID- 11324519
TI  - [The different responses to anoxia in cultured CA1 and DG neurons from newborn
      rats].
AB  - Tissue culture from hippocampal CA1 or dentate gyrus (DG) region was established
      on the basis of previous neuronal culture technique. The viability, intracellular
      calcium concentration and brain-derived neurotrophic factor (BDNF) mRNA
      expression of the two kinds of neurons after anoxia were observed in the counting
      in the confocal microscopic field and in situ hybridization. It is found that DG
      neurons are not only more resistant to anoxia, but also have a stronger ability
      to keep calcium homeostasis and to express BDNF mRNA than CA1 neurons.

PMID- 11324520
TI  - [Pupillary responses evoked by spatial patterns].
AB  - Human pupillary responses evoked by visual spatial patterns were investigated.
      Experimental data revealed that: (1) pupillary constriction can be induced not
      only by increment of luminance but also by change of gratings or checkerboards
      without change of space-averaged luminance; (2) constriction amplitude increases
      with increasing difference of spatial frequency; (3) pupillary response can be
      evoked by changing from uniform brightness to checkerboard patterns or from
      checkerboard to darkness, without any increment of the local luminance. These
      results indicate that the human pupillary response system is not merely
      controlled by luminous flux but also receives and processes visual pattern
      information.

PMID- 11324521
TI  - [Study on delayed rectifier K+ current of rabbit vascular smooth muscle cells and
      comparison with cloned Kv1.5 channel].
AB  - Whole cell patch-clamp recording techniques were used to compare the
      electrophysiological properties between delayed rectifier K+ current of rabbit
      vascular smooth muscle cell (VSMC) and the cloned Kv1.5 channel. When VSMC is
      clamped at -40 mV, depolarizing the membrane potential at increasing steps of 10
      mV could evoke a series of outward potassium currents without any deactivation.
      The V1/2 of the activation curve was 27.2 mV. The currents decrease obviously
      after adding 100 mmol/L TEA or 1 mmol/L 4AP in the perfusate. When the
      concentration of extracellular Ca2+ was decreased from 1.5 mmol/L to 0.5 or 0
      mmol/L, the currents did not show much change, while in HBK7 (cloned Kv1.5
      channel cell) held at -80 mV, similar steparise depolarization could also produce
      a series of outward potassium currents without any deactivation decayed. V1/2 of
      the activation was 0.8 mV. 4AP inhibited the cloned channel current with IC50 of
      7.3 mmol/L, showing neither frequency- or use-dependence. TEA (30, 100 and 300
      mmol/L) reduced the current by 28.6%, 37.4% and 46.3% respectively. Quinidine
      (0.1 and 1 mmol/L) decreased it by 29.7% and 37.4%. These results show what we
      have recorded in isolated rabbit vascular smooth muscle cells is the delayed
      rectifier potassium currents which are different in electrophysiological and
      pharmacological properties from those of cloned Kv1.5 channel current.

PMID- 11324522
TI  - [Changes of activities of MLCK and dephosphatase in different arterial vessels
      from hypertensive rats].
AB  - The changes of activities of myosin light chain kinase (MLCK) and Ca2+/CaM-PP in
      different arterial vessels from hypertensive and normotensive rats were studied.
      The results were as follows. The MLCK activity of different arteries of
      spontaneous hypertensive rats (SHR) was different with the order of aorta (A) >>
      caudal artery (CA) >> mesenteric artery (MA), while in WKY rats the order of
      activity among different arteries is A << CA and MA and MA Ca2+/CaM-PP is
      obviously higher than in SHR. In renal hypertensive rats the activities of
      Ca2+/CaM-PP in different arteries are not quite different from those of the
      Wistar rats. The above results suggest that higher activities of MLCK or/and
      lower activity might be related to vasocontraction and hypertension.

PMID- 11324523
TI  - [The role of G protein, protein kinase C and Na(+)-H+ exchanger in endothelin-1
      induced cardiomyocyte hypertrophic responses].
AB  - Endothelin-1 (ET-1) has been shown to be a potent growth factor and to induce
      cardiac hypertrophy. In the present study, we examined the role of G protein,
      protein kinase C (PKC) and Na(+)-H+ exchanger in ET-1-induced cardiac hypertrophy
      in cultured neonatal rat cardiac myocytes. ET-1 (10(-10)-10(-7) mol/L) induced
      promotion of 3H-leucine incorporation, increase in cell protein content and cell
      surface area in a dose-dependent manner with EC50 value of 5.2 x 10(-10), 5.2 x
      10(-10) and 7.3 x 10(-10) mol/L respectively. All of these ET-1-induced
      cardiomyocyte hypertrophic responses were completely blocked by pretreatment with
      staurosporine (2 nmol/L), a protein kinase C inhibitor, and stimulated by 4
      phorbol, 12-myristate, 13-acetate (PMA) (10(-8)-10(-6) mol/L), a protein kinase C
      activator, in a dose-dependent manner. Pretreatment of amiloride (10(-4) mol/L),
      a Na(+)-H+ exchange inhibitor completely inhibited the ET-1-induced, but not PMA
      induced cardiomyocyte hypertrophic responses. The ET-1-induced increase in
      cardiomyocyte protein synthesis and cell surface area was significantly inhibited
      by pretreatment with pertussis toxin (150 ng/ml). These results suggest that ET-1
      induced cardiomyocyte hypertrophy was linked with pertussis toxin sensitive G
      protein, and PKC and Na(+)-H+ exchange may be an important intracellular
      signaling transduction pathway during ET-1-induced cardiac hypertrophy in
      cultured neonatal rat cardiac myocytes.

PMID- 11324524
TI  - [Effect of calcium overload and platelet activating factor on calcitonin gene
      related peptide release from lung tissue].
AB  - The level of calcitonin gene related peptide (CGRP) in plasma and pulmonary
      lavage fluid was tested by radio-immunoassay on intestinal ischemia/reperfusion
      (I/R) injured rat. The results showed that plasma CGRP after I/R was 161.3% more
      than control, and 117.8% when pre-treated with platelet activating factor (PAF)
      receptor antagonist SR27417A before injury but no obvious changes were observed
      in the sham group. Meanwhile, CGRP was reduced by 17.4% in pulmonary lavage fluid
      in I/R animal and elevated by 97.9% in SR27417A pre-treated animal, compared with
      normal control. Furthermore, it was demonstrated that CGRP release from lung
      tissue was enhanced concentration-dependently by calcium ionophores A23187 or
      PAF, as a result of blockage by phospholipase A2 inhibitor p-BPB or SR27417A
      respectively. In vitro experiment, CGRP in pulmonary lavage fluid was 144.6% more
      than control when pre-treated with SR27417A and 114.6% less than that treated
      with A23187 only, even 14.8% less than control. Much the same, CGRP release was
      13.7% less than that treated with PAF and was 55.6% more than control when pre
      treated with SR27417A only. All these results indicated that (1) CGRP was
      significantly increased in plasma but without obvious changes in pulmonary lavage
      fluid following I/R injury; (2) lung tissue CGRP release may be related with Ca2+
      increase in cells or phospholipase A2 activation as well as PAF increase; (3)
      SR27417A was a kind of strong reagent, which may promote CGRP release in vivo and
      in vitro, but block the effect of PAF on CGRP release.

PMID- 11324525
TI  - [Neuronal activity of monkey dorso-lateral premotor cortex during tasks of figure
      recognition guided motor sequence vs memorized spatial motor sequence].
AB  - In the last 2-3 decades the role of the premotor cortex (PM) of monkey in
      memorized spatial sequential (MSS) movements has been amply investigated.
      However, it is as yet not known whether PM participates in the movement sequence
      behaviour guided by recognition of visual figures (i.e. the figure-recognition
      sequence, FRS). In the present work three monkeys were trained to perform both
      FRS and MSS tasks. Postmortem examination showed that 202 cells were in the dorso
      lateral premotor cortex. Among 111 cells recorded during the two tasks, more than
      50% changed their activity during the cue periods in either task. During the
      response period, the ratios of cells with changes of firing rate in both FRS and
      MSS were high and roughly equal to each other, while during the image period, the
      proportion in the FRS (83.7%) was significantly higher than that in the MSS
      (66.7%). Comparison of neuronal activities during same motor sequence of two
      different tasks showed that during the image periods PM neuronal activities were
      more closely related to the FRS task, while during the cue periods no difference
      could be found. Analysis of cell responses showed that the neurons with longer
      latency were much more in MSS than in FRS in either cue or image period. The
      present results indicate that the premotor cortex participates in FRS motor
      sequence as well as in MSS and suggest that the dorso-lateral PM represents
      another subarea in function shared by both FRS and MSS tasks. However, in view of
      the differences of PM neuronal responses in cue or image periods of FRS and MSS
      tasks, it seems likely that neural networks involved in FRS and MSS tasks are
      different.

PMID- 11324526
TI  - [Effect of AVP(4-8) administration on Ca2+/CaM-dependent protein kinase II
      autophosphorylation in rat brain].
AB  - The extent increase of Ca2+/CaM-dependent protein kinase II (CaMK II)
      autophosphorylation in various brain regions of rat reached a maximum value, one
      hour after s.c. administration of AVP(4-8). The increase in the cortex amounted
      to 192% of the control (P < 0.001), while in the hippocampus only 40% (P < 0.05).
      The autophosphorylation of CaMK II was dependent on both Ca2+ and CaM. Western
      blotting with anti-CaMK II alpha monoclonal antibody showed that the content of
      CaMK II alpha in cortex did not show detectable change in 1 h as compared to the
      control group. ZDC(C)PR, an antagonist of AVP(4-8), markedly blocked the effect
      of AVP(4-8), suggesting that AVP (4-8) stimulated CaMK II autophosphorylation is
      mediated through its receptor.

PMID- 11324527
TI  - [Expression of opioid-receptor-like receptor (ORL1) gene in rat brain].
AB  - In situ hybridization with a digoxigenin-labeled oligonucleotide probe was used
      to investigate the expression of opioid-receptor-like receptor (ORL1) gene in rat
      brain. It was observed that ORL1 mRNA is widely expressed in many regions of rat
      brain, particularly in cerebral cortex, thalamus, hypothalamus, amygdala,
      hippocampus, septum, habenula, periaqueducted gray, raphe nuclei and locus
      coeruleus structure. These findings suggest that ORL1 receptor may participate in
      modulating a number of physiological functions in the brain in addition to pain.

PMID- 11324528
TI  - [The inhibitory effects of artemisinin-derivatives on Na+ and K+ channels in
      comparison with those of procaine].
AB  - Some derivatives of artemisinin have been shown to have local anesthesia action.
      By using patch-clamp whole cell recording configuration, the effects of five
      artemisinin-derivatives on the voltage-gated INa and IK have been studied on
      differentiated NG108-15 cells with reference to procaine. The results showed that
      all the five artemisinin-derivatives clearly inhibited the voltage-gated sodium
      current (INa) of the cells in a dose-dependent manner and the effect was
      partially reversibly. Among the five artemisinin-derivatives, SM541 has been
      shown to be most potent, approaching that of procaine. However, 300 mumol/L
      procaine showed only a slight inhibition of IK, whereas all the five derivatives
      at the same concentration not only decreased IK clearly, but also accelerated its
      inactivation. Except for SM541, the inhibitory effects on IK decreased rapidly
      with perfusion of the rest 4 derivatives.

PMID- 11324529
TI  - [Properties of the GM-CSF-induced outward K+ current in murine peritoneal exudate
      macrophages].
AB  - Whole-cell patch-clamp technique was used to study the changes of ionic currents
      in murine peritoneal exudate macrophages (PEMs) prestimulated with granulocyte
      macrophage colony-stimulating factor (GM-CSF, 16 ng/ml) for periods from 0.5 up
      to 6 d. The GM-CSF-treated PEMs developed a GM-CSF-induced transient inactivating
      outward K+ current (IA). IA showed steady-state inactivation over the
      physiological voltage range and possessed frequency dependence of inactivation
      when depolarizing pulses were applied at a frequency of 0.5 Hz. IA was
      selectively inhibited by extracellular 4-AP (3 mmol/L). When [Ca2+]i was
      increased (from pCa 8 to 6), the amplitudes of IA were depressed significantly.
      When the PEMs were exposed to cycloheximide (0.3 microgram/ml), a protein
      synthesis inhibitor, for 12 h, IA expression was completely suppressed. It was
      notable that the changes of the current expression, activation behavior and
      kinetic properties occurred during GM-CSF treatment. When PEMs were pretreated
      for a 2-d period, the frequency of IA expression reached a peak value (55% in a
      total of 27 cells), PEMs exhibited the highest density of the corresponding
      channel proteins, half-maximal activation of IA was most easily achieved with a
      value of -27.55 mV, and the time course of activation and inactivation during
      depolarization proceeded rapidly. However, along with continuous incubation with
      GM-CSF, the number of PEMs expressing IA decreased, the channel proteins were
      down regulated constantly, the activation curve for IA shifted to positive
      potentials, and the activation time and inactivation time of IA slowed down.
      These results indicated that GM-CSF could induce a transient inactivating outward
      K+ current in PEMs, which may have a close relation to the state of functional
      activation of macrophages primed with GM-CSF.

PMID- 11324530
TI  - [Apamin sensitive component of Ca(2+)-activated K+ current of
      afterhyperpolarization, IAHP, in dorsal root ganglion neurons in rat].
AB  - Whole-cell voltage clamp technique was used to record the tail current in freshly
      isolated dorsal root ganglion (DRG) neurons of rat with an aim to investigate
      whether these neurons possess an apamin sensitive component of Ca(2+)-activated
      K+ current, IAHP. The results are as follows: (1) the amplitudes of the tail
      currents increased from 9.3 +/- 2.8 pA to 64.1 +/- 3.4 pA (P < 0.001) when the
      depolarizing duration was increased from 1 ms to 180 ms; (2) the amplitudes of
      the tail current were reduced when repolarizing pulses were applied, with a
      reversal potential of about -63 mV; (3) the amplitude of the tail current was
      significantly depressed or even almost completely blocked by extracellularly
      applied 500 mumol/L Cd2+ or intracellularly applied 11 mmol/L EGTA; (4) the
      amplitudes of the tail currents were decreased by about (26.32 +/- 3.9)% (P <
      0.01) after 200 nmmol/L apamin was extracellularly applied; and (5) the fast
      component of the tail current was sensitive to 10 mmol/L TEA while the slow
      component was insensitive. These results suggest that an apamin sensitive
      component of Ca(2+)-activated K+ current may be present in afterhyperpolarization
      of DRG neurons.

PMID- 11324531
TI  - [Modulatory effects of endothelin on carotid baroreflex in anesthetized rats].
AB  - Modulatory effects of endothelin (ET) on carotid baroreflex were examined in 27
      anesthetized rats with isolated carotid sinus perfusion. The results obtained
      were as follows: (1) By perfusing with 1 nmol/L ET-1, the functional curve of
      carotid baroreflex (FCCB) was shifted to the left and downward with an increase
      in its peak slope (PS) from 0.40 +/- 0.02 to 0.51 +/- 0.02 kPa/kPa (P < 0.01),
      while the reflex decrease of mean arterial pressure (RD) was increased from 5.66
      +/- 0.23 to 6.76 +/- 0.22 kPa (P < 0.01). The above results indicated that this
      dose of ET-1 facilitated the carotid baroreflex. (2) On the contrary, by
      perfusing with 10 nmol/L of ET-1, FCCB was shifted to the right and upward with a
      decrease of PS to 0.28 +/- 0.01 kPa/kPa (P < 0.01), while RD was decreased to
      4.16 +/- 0.19 kPa (P < 0.01). In response to perfusion with 100 nmol/L ET-1, FCCB
      was further shifted to the right and upward with a marked decrease of PS to 0.19
      +/- 0.03 kPa/kPa (P < 0.001), and RD was conspicuously decreased to 3.33 +/- 0.38
      kPa (P < 0.001). These results showed that ET-1 at the doses of 10 or 100 nmol/L
      exerted an inhibitory action on baroreflex. (3) Selective ETA receptor blocker
      BQ123 (0.15 mumol/L) might abolish the effects of ET-1 (10 nmol/L) on baroreflex.
      (4) Preperfusing with KATP channel antagonist glibenclamide (10 mumol/L) could
      also eliminated the effects of ET-1. Taken together, it is suggested that ET-1
      exerts a dual effects on baroreflex, being facilitatory at lower dose and
      inhibitory at higher dose. The latter effect is mediated by ETA receptor, in
      which KATP channels may be involved.

PMID- 11324532
TI  - [Role of rostral ventrolateral medulla in the pressor response to
      intraventricular (4th) injection of substance P].
AB  - Experiments were done in rabbits anaesthetized with urethane and immobilized
      under artificial respiration. It was found that substance P (SP, 0.8 ng/kg
      dissolved in 100 microliters artificial cerebro-spinal fluid, CSF) injected into
      the 4th ventricle induced either a rise or a drop of pulmonary arterial pressure
      (PAP) with predominated pressor response. In addition, a rise in carotid arterial
      pressure (CAP) and reduction in heart rate (HR) were also observed, whereas no
      significant alteration in PAP, CAP and HR was observed. Microinjection of SP
      receptor antagonist [D-Pro2, D-Phe7, D-Trp9]--SP (5-10 ng dissolved in 0.5
      microliter CSF) or phentolamine (2-3 micrograms dissolved in 0.5 microliter CSF)
      into the bilateral rostral ventrolateral medulla (rVLM) prior to intraventricular
      injection of SP could block the SP-induced pressor responses in pulmonary and
      carotid arteries, while microinjection of SP receptor antagonist or phentolamine
      into bilateral caudal ventrolateral medulla (cVLM) at the same dosage had no
      effect. The results show that SP-induced pulmonary and carotid pressor responses
      may be mediated through SP-receptor and alpha-adrenergic receptors in the rostral
      ventro-lateral medulla (rVLM).

PMID- 11324533
TI  - [The relationship between cytosolic Ca2+ and two kinds of granule number in
      activated platelets].
AB  - The numerical density (Nv) of the alpha-granule (alpha G) and dense granule (dG)
      measured by using electron microscopic morphometry and the cytosolic free calcium
      concentration ([Ca2+]i) by using Ca-fluorescent indicator were observed for
      studying the relationship of [Ca2+]i and Nv of alpha G and dG in platelets
      activated by A23187, thrombin or ADP. The results showed that the [Ca2+]i rose
      markedly by A23187. Thrombin or ADP could also induce an increase of [Ca2+]i
      concentration-dependently. Under 3 different degrees of activation induced by
      different agonists, the close relationship between Nv of both granules, alpha G
      and dG, and [Ca2+]i in platelets was found (Pr(alpha G) < 0.05, Pr(dG) < 0.01).
      These findings indicate that the increase in [Ca2+]i may enhance the secretion of
      alpha G and dG.

PMID- 11324534
TI  - [Effect of Arg-Gly-Asp-Ser (RGDS) peptide on ADP-induced signal transduction of
      activated rat platelet].
AB  - The purpose of this work was to investigate the effect of Arg-Gly-Asp-Ser (RGDS)
      peptide on platelet aggregation, protein phosphorylation, protein kinase C (PKC)
      and mitogen-activated protein kinase (MAPK) activity during platelet activation.
      Experiments were performed on ADP activated rat platelets in vivo. Results showed
      that 50 mumol/L ADP, in addition to inducing platelet aggregation, obviously
      enhanced not only PKC and MAPK activities but also 95 and 66 kD protein
      phosphorylation. When platelets and ADP were incubated together with 50, 100, 200
      mumol/L RGDS peptide it was found that the latter markedly inhibited ADP
      activated platelet aggregation and activation of PKC and MAPK, both in a
      concentration-dependently manner. RGDS peptide also inhibited 95 and 66 kD
      protein phosphorylation concentration-dependently and went positively with its
      activation of PKC and MAPK. The above result suggested that the antithrombotic
      effect of RGDS peptide was probably mediated through its effect on intracellular
      signal transduction in the ADP activation of platelets.

PMID- 11324535
TI  - [Changes of angiotensin II autocrine by cultured pulmonary artery smooth muscle
      cells exposed to anoxia].
AB  - Alterations of autocrine function of pulmonary arterial smooth muscle cells
      (PASMCs) might play an important role in development of hypoxic pulmonary
      hypertension (HPH). To test this hypothesis, the effects of hypoxia on
      angiotensin II (AT II) secretion by cultured new born bovine PASMCs were
      investigated. AT II secretion decreased significantly when PASMCs were incubated
      under 2.5% O2 hypoxic condition for 3 to 48 h (P < 0.01 vs control), but
      decreased further under anoxic condition (P < 0.01 vs control and 2.5% O2 group).
      Nitric oxide (NO) donor SIN-1 inhibited AT II secretion significantly under
      normoxic condition, but NO synthase inhibitor L-nitro-arginine (LNA) eliminated
      the inhibitory effect of anoxia on AT II autocrine and promoted AT II release. It
      was also found that the concentration of cGMP in PASMCs increased significantly
      (P < 0.01) at 24 h incubation in 0% O2, an effect that can be attenuated by LNA.
      Hypoxia stimulated 3H-TdR incorporation of PASMCs significantly (P < 0.001),
      while captopril exerts an inhibition in normoxic condition (P < 0.001), but
      without effect under hypoxic condition. The above results suggest that hypoxia
      can inhibit AT II secretion by inducing endogenous NO production in PASMCs. AT II
      autocrine is not involved in hypoxic proliferation of PASMCs, but a decrease of
      AT II may contribute to prevention of the development of HPH.

PMID- 11324536
TI  - [Modulations of proliferation between in vitro pulmonary artery endothelial cells
      and smooth muscle cells under hypoxia].
AB  - Vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs) are
      structurally and functionally closely connected. Their interactions may play
      important roles in the development of hypoxic pulmonary artery hypertension. In
      the present study, mitogenic regulations between cultured new bovine pulmonary
      arterial endothelial cells (PAECs) and pulmonary arterial smooth muscle cells
      (PASMCs) under both normoxic and hypoxic conditions were investigated. Cell
      proliferation was assessed by 3H-thymidine incorporation and flow cytometry.
      Normoxic conditioned medium (CM) from cultured PASMCs inhibited 3H-thymidine
      incorporation of PAECs by 58% (P < 0.01), but normoxic or hypoxic CM from PAECs
      promoted or inhibited 3H-thymidine incorporation of PASM by 60% and 27%
      respectively (P < 0.01). When mixed PAECs and PASMCs were cultured for 24 h,
      relative 3H-thymidine incorporation of the mixed cells decreased by 22% (P < 0.01
      vs monoculture) under normoxic condition, and increased by 75% or 44% under 0% O2
      or 2.5% O2 (P < 0.01 vs normoxic mixculture). When PAECs and PASMCs were
      cocultured in either normoxic or hypoxic conditions, proliferation of PAECs was
      inhibited while that of PASMs was stimulated significantly (P < 0.01), as
      compared with that of homotypic cultured cells. These findings suggest that PAECs
      and PASMCs may mutually regulate their proliferation each other, and this mutual
      modulation may be changed under hypoxic condition.

PMID- 11324537
TI  - [Decrease of calcitonin gene-related peptide release from mesenteric arterial bed
      in diabetic rats and effect of nitric oxide].
AB  - Our previous work has shown that endotoxin triggers the release of calcitonin
      gene-related peptide (CGRP) from the mesenteric arterial bed, which is partially
      mediated by nitric oxide. In the present study, the changes of endotoxin-induced
      CGRP release from the isolated mesenteric arterial bed and the CGRP mRNA levels
      in dorsal root ganglia (DRG) of diabetic rats were studied in relation to the
      effect of nitric oxide. CGRP level in perfusate and the steady-state level of
      mRNA for CGRP in DRG were determined by RIA and semi-quantitatively by RT-PCR.
      The results showed that endotoxin (1-25 micrograms/ml) accumulated in perfusate
      caused concentration-dependent release of CGRP, which was significantly decreased
      in mesenteric arterial bed of diabetic rats. As compared with age-related
      control, the endotoxin (10 and 25 micrograms/ml) -induced CGRP release in
      diabetic rats was attenuated by 27% and 40%, respectively. L-NAME, an inhibitor
      of nitric oxide synthase, inhibited the effect of endotoxin in dose of 10 and 25
      micrograms/ml by 23% and 46%, respectively against the control rats. However,
      there was no inhibitory effect of L-NAME on endotoxin-induced CGRP release in
      diabetic rats. The CGRP mRNA level in DRG showed no significant difference
      between the two groups. These results indicate that the response of the isolated
      mesenteric arterial bed to endotoxin-induced CGRP release in diabetic rats is
      significantly lower than that in control. The mechanism, at least in part, is due
      to a decrease of nitric oxide mediated release of CGRP, rather than a decrease of
      CGRP gene expression.

PMID- 11324538
TI  - [Absence of detubulation in frog twitch muscle fibres exposed to protein kinase C
      activator].
AB  - It has been shown that excitation-contraction(e-c) uncoupling occurred in frog
      twitch muscle fibres exposed to phorbol 12,13-dibutyrate (PDBu), a protein kinase
      C activator. To investigate if this uncoupling results from detubulation of the
      transverse tubules, intracellularly evoked action potentials were examined. The
      after-depolarization of the action potential, representing intact transverse
      tubules was gradually abolished by osmotic detubulation, while those obtained
      from the fibres incubated in 1 mumol/L PDBu for 12 or 24 h still possessed the
      after-depolarization. Thus, it showed that the transverse tubules were still
      intact in frog twitch muscle fibres after exposure to PDBu. The mechanism of e-c
      uncoupling induced by PDBu remains to be clarified.

PMID- 11324539
TI  - [Inhibition of the expression of delta opioid receptor mRNA by long-term exposure
      of NG-108-15 cell line to delta opioid agonists].
AB  - We used the method of reverse transcription-polymerase chain reaction (RT-PCR) to
      observe the effects of long-term administration of peptide delta opioid receptor
      agonist DPDPE and non-peptide delta agonist BW373U86 on the mRNA expression of
      delta receptor and the possible difference between the two agonists. The results
      showed: (1) the level of delta receptor mRNA decreased significantly 24-48 h
      after administration of DPDPE; the effect of BW373U86 lasted only 24 h; and (2)
      DPDPE produced a significant decrease of delta-receptor mRNA at 10(-6) mol/L,
      whereas BW373U86 was effective only at 10(-5) mol/L. These results suggest that
      long-term administration of both peptide delta opioid receptor agonist (24, 48 h)
      and non-peptide delta opioid agonist (24 h) significantly decreased mRNA
      expression of delta opioid receptor and the effect of peptide agonist DPDPE seems
      to be stronger and last longer than that of non-peptide agonist BW373U86.

PMID- 11324541
TI  - [Modulatory action of alpha 2-adrenoceptor on calcitonin gene-related peptide
      release from rat mesenteric arterial bed].
AB  - The release of calcitonin gene-related peptide (CGRP) from peripheral terminals
      of sensory nerves was modulated via multiple mechanisms. In the present study,
      pharmacological agents were used to investigate the modulatory action of alpha 2
      adrenoceptor on endotoxin-induced CGRP release from isolated perfused rat
      mesenteric arterial bed. The results showed that UK14304 (3 x 10(-6) mol/L), a
      potent alpha 2-adrenoceptor agonist, significantly inhibited both basal and
      endotoxin-induced CGRP release by 22%-42%, while specific antagonist of alpha 2
      adrenoceptor yohimbine (10(-5) mol/L) blocked the effect of UK14304 completely.
      The data suggest that presynaptic alpha 2-adrenoceptor has an inhibitory effect
      on basal and endotoxin-induced CGRP release. Dysfunction of alpha 2-adrenoceptor
      in the late stage of endotoxic shock may be involved in the excess release of
      CGRP from the peripheral nerves.

PMID- 11324540
TI  - [Changes of K+ channel current in cerebellar cortical neuron of apoptosis induced
      with H2O2].
AB  - The neurons dissociated from the cerebellar cortex of neonatal SD rat were
      cultured, while the growth of non-neuron cells were suppressed by Ara-c.
      Apoptosis of the neurons were induced with H2O2. The changes of Ik were studied
      during apoptosis using the patch clamp technique in cell-attached configurations.
      The results are as follows: (1) the Ik amplitudes of the neurons were lower than
      that of normal at various corresponding clamp voltages; (2) the conductances,
      mean open time, open probability, long and short opening time constants were all
      lower, as compared with normal neurons. All these results indicate that the
      activities of K+ channels on cerebellar neurons decrease during apoptosis.

PMID- 11324542
TI  - [Effects of noradrenaline on delayed outward potassium current in isolated rat
      hepatocytes].
AB  - Heretofore no reports are available on the outward potassium currents in rat
      hepatocytes. Using whole-cell patch clamp technique, the effects of noradrenaline
      and other reagents on the delayed outward potassium current (IK) in isolated rat
      hepatocytes were investigated. The experimental results showed that the magnitude
      of IK was 2.85 +/- 1.21 nA at a command potential of +140 mV from a holding
      potential of -50 mV. Noradrenaline decreased IK distinctly. Isoprenaline and
      acetylcholine showed no effect on IK in isolated rat hepatocytes.

PMID- 11324543
TI  - [Neurokinin-1 receptor mediated formalin-induced c-fos expression in the rat
      spinal cord].
AB  - In the present work, the effects of tachykinin receptor antagonists on formalin
      induced c-fos expression in the rat spinal cord were studied by a combination of
      immunocytochemical and neuropharmacological methods. Formalin injected into a
      hindpaw of rat only resulted in c-fos expression in the ipsilateral dorsal horn
      neurons of the spinal cord. Fos-positive neurons were distributed mainly in
      medial parts of the lamina I and the outer lamina II. A moderate number of Fos
      positive neurons were present in laminae IV-V, and a few in the inner lamina II
      and in laminae III, VI and X. Selective NK-1 antagonist L-668, 169 (0.1, 1 and 10
      micrograms) administered intrathecally before injection of formalin into a
      hindpaw significantly reduced the number of Fos-labeled neurons in the dorsal
      horn in a dose-dependent manner (P < 0.01), while selective NK-2 antagonist L
      659, 877 (10 micrograms) and selective NK-3 antagonist SR-142, 801 (10
      micrograms) were ineffective (P > 0.05). Our results indicated that NK-1 receptor
      mediated formalin-induced c-fos expression in the spinal cord, suggesting NK-1
      receptor might play an important role in the spinal transmission of nociceptive
      messages.

PMID- 11324545
TI  - [Inhibition of GABA-activated currents in isolated rat DRG neurons by
      bradykinin].
AB  - In the present paper, the modulation of GABA-activated currents by bradykinin
      (BK) was studied in DRG neurons freshly isolated from rat using whole-cell patch
      clamp techniques. Among the neurons (n = 34) responding to GABA, 27 were
      sensitive to BK. Pre-application of BK, eliciting an inward current alone,
      inhibited GABA-activated current markedly. For example, 10(-6) mol/L BK
      suppressed GABA-activated current by about 30%. BK shifted the GABA dose-response
      curve downward obviously and depressed the maximal response to GABA by 1/3 or
      more while the Kd value was unchanged. The results suggest that BK inhibits GABA
      activated current noncompetitively in rat DRG neurons.

PMID- 11324544
TI  - [The relation between changes of nitric oxide synthase in hippocampus and
      activities of excitatory amino acid receptor during epilepsy].
AB  - The time course of alteration in neuronal nitric oxide synthase (nNOS) and the
      influence of glutamate receptor antagonists on immunoreactivity of nNOS were
      investigated immunohistochemically in rat hippocampus during penicillin-induced
      epilepsy. It was found that nNOS-like immunoreactivity in hippocampus increased
      at 4 h after initiation of seizure and reached a peak at 24 h. When MK-801 (6
      micrograms) and DNQX (4 micrograms) were injected respectively into hippocampus
      20 min before administration of penicillin, seizure was reduced in strength.
      Meanwhile, the nNOS-like immunoreactivity in hippocampus was decreased, compared
      with the group which were administered penicillin alone. These results suggest
      that the increase of nitric oxide may be related to the injury of neurons during
      and after epilepsy; the changes' of nNOS may be related to the activity of NMDA
      and non-NMDA receptors. Neuron protective effect of MK-801 and DNQX may be in
      part mediated by nNOS.

PMID- 11324546
TI  - [Inhibition of signal transduction pathways of endothelin-1-induced proliferation
      of vascular smooth muscle cells by nitric oxide].
AB  - The signal transduction pathways of the inhibitory effect of nitric oxide (NO) on
      endothelin (ET)-induced proliferation of vascular smooth muscle cells (VSMCs)
      were studied. 3H-thymidine (TdR) incorporation, mitogen-activated protein kinase
      (MAPK) activity and protein kinase C (PKC) activity of cultured VSMCs of rabbits
      thoracic aorta were measured in the presence of either NO precursor L-arginine (L
      Arg) or NO donor 3-morpholino sydnonimine-hydrochloride (SIN-1), or ET-1 alone or
      with L-Arg or SIN-1. The results show: (1) ET-1 (10(-8) mol/L) significantly
      increased VSMCs 3H-TdR incorporation (5 times, P < 0.01), MAPK activity (4 times,
      P < 0.01) and PKC activity (3 times, P < 0.01), as compared with control. L-Arg
      or SIN-1 alone was without effect on 3H-TdR incorporation, MAPK activity and PKC
      activity. (2) When ET-1 and L-Arg (2, 5, 10 mmol/L) were simultaneously
      administered, 3H-TdR incorporation and activity of both MAPK and PKC were all
      significantly decreased in comparison with the ET group. (3) When ET-1 + SIN-1
      (5, 10, 50 mumol/L), the effects coincide with those of the ET-1 + L-Arg groups.
      These findings indicate that NO inhibition of the signal transduction pathways of
      the ET-1-induced proliferation of VSMCs may be mediated by the inhibition of ET-1
      induced activation of both PKC and MAPK.

PMID- 11324547
TI  - The changes of AP-1 DNA binding activity and components in hippocampus of seizure
      sensitive rat induced by kainate.
AB  - Seizure-sensitive Fisher 344 rats were prepared 7 d after seizure episodes
      induced by a single subcutaneous administration of convulsive dose (7.5 mg/kg) of
      kainic acid. The activator protein-1 (AP-1) DNA binding activity and its
      components in the hippocampus of such rats were examined by Gel shift, Super
      shift and Western blot assay. Gel shift assay showed that the basal level of AP-1
      DNA binding activity was significantly higher than that of control rat
      hippocampus. Super-shift showed that only Fra and Jun D antibodies could super
      shift AP-1 complex to a higher position. It suggested that the AP-1 complex was
      composed of Fra and Jun D in hippocampus of the seizure-sensitive rats. Western
      blot analysis further confirmed that Jun D proteins contained components of 43,
      39 and 28 kDa. When secondary seizure stimulations were given to seizure
      sensitive rats, the AP-1 DNA binding activity was attenuated and the components
      of AP-1 proteins changed transiently. In light of our results and those of
      literature, it appears that all the mentioned changes may play an important role
      in induction of long-lasting enhancement in seizure susceptibility.

PMID- 11324548
TI  - [The central mechanism of the high frequency component in heart rate variability
      in rat].
AB  - Experiments were performed on 15 Sprague-Dawley rats to detect the effect of
      artificial ventilation of different frequencies on the high frequency component
      of heart rate variability (HRV) by autoregressive modeling with Burg algorithm.
      With continuous or intermittent electrical stimulation, different patterns of
      regulating activity of nucleus ambiguus in medulla on HRV were observed. Fast
      Fourier transform was used to analyze the coherence between neuronal discharge
      with respiratory rhythm in rostral ventrolateral medulla (rVLM) and HRV. The
      results showed that (1) the central frequency of high frequency (HF) component of
      HRV were moved closely with frequencies of artificial ventilation, (r = 0.83, P <
      0.0001); (2) there was a favorable coherence between neuronal discharge with
      respiratory rhythm in rVLM and HRV in HF on spectrum, (k2 = 0.854 +/- 0.1); (3)
      the area of HF component in HRV was increased significantly during intermittent
      electrical stimulation of nucleus ambiguus in medulla. The central frequency of
      HF component in HRV was influenced mainly by frequencies of respiration. These
      results indicate a significant correlation between the HF in HRV and neuronal
      discharge with respiratory rhythm in rVLM, suggesting that rVLM participates in
      the regulation of HRV. The HF component of HRV may reflect mainly the fluctuating
      activity of vagal center. Coherence analysis of two signals provides a new method
      to confirm the type and interaction of neurons in the central cardiovascular
      system.

PMID- 11324549
TI  - L-phenylalanine and smooth muscle cell proliferation from SHR and WKY rats.
AB  - Cell growth and proliferation were evaluated in cultured vascular smooth muscle
      cells (VSMCs) isolated from spontaneously hypertensive rat (SHR) and normotensive
      Wistar-Kyoto (WKY) rat aortae by measuring [3H]-thymidine incorporation into
      newly synthesized DNA and by determining cell number, respectively. The results
      showed that in cultures from both rat strains (1) serum-, basic fibroblast growth
      factor (bFGF)- and thrombin-induced DNA synthesis were inhibited by L
      phenylalanine dose-dependently; (2) L-phenylalanine inhibited cell proliferation
      in response to serum in a concentration-dependent manner; (3) L-phenylalanine
      inhibited serum-induced proto-oncogene c-fos and c-myc expression; (4) L
      tyrosine, L-histidine and D-phenylalanine failed to mimic the inhibitory effect
      of L-phenylalanine. All these data demonstrate that L-phenylalanine could exert a
      direct and specific antiproliferative effect on VSMCs suggesting that such effect
      can account for the antihypertensive action of this amino acid observed in SHR.

PMID- 11324550
TI  - [Effects of Cs on automaticity and pacemaker current If and Ik in rabbit sinus
      node cells].
AB  - Conventional microelectrode and perforated patch clamp techniques were employed
      to study the pacemaker mechanisms in enzyme-isolated rabbit sinus node cells. 2
      mmol/L Cs had little effect on automatic discharge of the SA node and the slope
      of diastolic depolarization. Cs blocked both If and slope conductance increase
      but left Ik largely unaffected. The results suggest that If is not essential for
      the first stage of automatic activity of the rabbit SA node.

PMID- 11324551
TI  - Angiotensin II-induced apoptosis in cultured adult rat ventricular myocytes.
AB  - Angiotensin II (Ang II)-induced apoptosis was demonstrated for the first time in
      cultured adult rat ventricular myocytes (ARVMs) isolated by retrograde heart
      perfusion with Krebs-Henseleit bicarbonate (KHB) buffer containing collagenase
      and hyaluronidase. ARVMs incubated with 10 mumol/L Ang II for 48 h showed
      morphological features of apoptosis (cellular shrinkage, condensation of
      cytoplasm) and a characteristic "ladder" of DNA bands representing integer
      multiples of the internucleosomal DNA length about 180-200 bp, which became more
      evident with further incubation up to 72 h. With shorter incubation time (< or =
      24 h) or at a lower Ang II concentration (< 10 mumol/L), such changes failed to
      occur. This effect of Ang II could be abolished by losartan (10 mumol/L),
      verapamil (1 mumol/L) or staurosporine (10 nmol/L). The above results indicate
      that Ang II-induced apoptosis in ARVMs may be mainly mediated by Ang II type I
      (AT1) receptors with [Ca2+]i and protein kinase C (PKC) playing a critical role.

PMID- 11324552
TI  - Expression of calcitonin gene-related peptide (CGRP) mRNA in rat lymphocytes.
AB  - We recently found that calcitonin gene-related peptide (CGRP)-like
      immunoreactivity was present in lymphocytes of rat thymus and lymph node. In
      order to investigate whether these cells were capable of synthesizing CGRP, CGRP
      mRNA of rat dorsal root ganglia, thymocytes and mesenteric lymph node lymphocytes
      were determined by reverse transcription and polymerase chain reaction (RT-PCR)
      utilizing synthetic oligonucleotides bracketing a portion of the calcitonin/CGRP
      gene. A discrete band of the expected size of 90 base pairs was found in the
      dorsal root ganglia (positive control), and in both thymocytes and mesenteric
      lymph node lymphocytes. These data strongly suggest that CGRP is not only an
      important neuropeptide, but it is also synthesized in lymphocytes of both thymus
      and lymph nodes, which is identical to that in sensory neurons. CGRP from
      lymphocytes may act as an immunomodulator and serve as a common ligand in immune
      and nervous systems.

PMID- 11324553
TI  - [Regulatory role of 5-hydroxytryptamine and motilin in migrating motor complex of
      small bowel in dogs].
AB  - Migrating motor complex (MMC) was recorded by chronically implanted strain gauge
      transducers on the serosa of small bowel in conscious dogs. Two silastic
      catheters for injecting drugs and taking blood samples were put respectively in a
      vena jugularis externa and in a jejunal artery which perfused a 10-15 cm
      intestinal segment. The present study was undertaken to observe the effect of
      drugs administered intravenously and intraarterially on MMC and alterations of
      plasma 5-hydroxytryptamine (5-HT) and motilin in different phases of MMC. The
      results showed: (1) Levels of plasma 5-HT and motilin showed cyclical
      fluctuations in different phases of MMC, and 5-HT reached peak before peak of
      motilin. Plasma 5-HT level reached a peak [(41.2 +/- 1.3) ng/ml] in the later
      period of phase II, which increased significantly as compared with phase I [(22.4
      +/- 1.1) ng/ml] (P < 0.01), but plasma motilin level had a peak [(580.0 +/- 30.2)
      pg/ml] in phase III of MMC, which was higher than that in phase I [(140.0 +/-
      21.0) pg/ml] (P < 0.01). (2) Intravenous motilin and intraarterial 5-HT and
      motilin could induce phase III contraction in the canine proximal small bowel and
      in the perfused segment respectively. Amplitude of contractions caused by motilin
      was higher than that by 5-HT in the perfused segment. (3) 5-HT receptor
      antagonist, motilin antiserum, 5,6-dihydroxytryptamine and tetrodotoxin perfused
      intra-arterially inhibited expression of MMC in the perfused segment and its
      caudal propagation. We conclude that plasma 5-HT and motilin may be dominant
      factors which initiate MMC of canine small bowel, and 5-HT peak appears before
      peak of motilin. 5-HT neurons and motilin neurons in enteric nervous system may
      play an important role in controlling MMC of canine small bowel.

PMID- 11324555
TI  - [In vitro analysis of cross immunoreaction between CGRP and endotoxin in CGRP
      radioimmunoassay].
AB  - In the present study, the effect of endotoxin on the radioimmunoassay of
      calcitonin gene-related peptide (CGRP) was investigated by method of
      radioimmunoassay. The results showed a competitive combination of endotoxin at
      high-concentrations (higher than 5 micrograms/ml) with multiclonal antibody of
      CGRP, and the cross immunoreaction ratio between CGRP and endotoxin was 5.6 x 10(
      6). The mixed endotoxin in samples was effectively cleared through C18 column
      purification. The data indicated that endotoxin interfered CGRP radioimmunoassay
      in vitro at high concentrations. The influence of endotoxin on CGRP
      radioimmunoassay can be avoided through C18 column purification for the endotoxin
      containing samples.

PMID- 11324554
TI  - [Localization and expression of TR3 orphan receptor in mouse testis].
AB  - By means of in situ hybridization and immunohistochemistry, the expression and
      cellular localization of orphan receptor TR3 and its mRNA were observed. The
      results showed that both TR3 and its mRNA were expressed in a significant amount
      in mouse testis, and the expression level of TR3 mRNA was different in different
      seminiferous tubules. TR3 mRNA was specifically expressed in germ cells, mainly
      in spermatogonia and less advanced primary spermatocytes, whereas TR3 receptor
      protein was mainly localized in germ cells. It is suggested that TR3 may play an
      important role in regulating the early stage of germ cell development in mice.

PMID- 11324556
TI  - [Regulation of ACTH4-9 analogue on the Ca2+ level of mouse hippocampal
      synaptosomes].
AB  - The effect of ACTH4-9 analogue Org2766 on the [Ca2+]i level of mouse hippocampal
      synaptosomes was studied. Synaptosomal free calcium concentration ([Ca2+]i) and
      45Ca2+ uptake were measured respectively by spex cation measurement system and
      Beckman LS-9800 liquid scintillation spectrometer. Low dose of Org2766 did not
      change synaptosomal [Ca2+]i level, but decreased 45Ca2+ uptake. High dose of
      Org2766 increased [Ca2+]i without affecting 45Ca2+ uptake. Low dose of Org2766
      inhibited the anisomysin-induced increase of synaptosomal [Ca2+]i while high dose
      had no effect. These results suggest that the regulation of Org2766 on
      hippocampal synaptosomal Ca2+ level may be achieved by inhibiting the Ca2+ influx
      and increasing the release of synaptosomal calcium pool.

PMID- 11324558
TI  - [Angiotensin II type 2 receptor gene deletion does not affect renin-angiotensin
      system].
AB  - It has been postulated that Angiotensin II type 2 receptor (AT2) functionally
      antagonizes type 1 (AT1) receptor. In the present study, we investigated whether
      gene deletion of AT2 receptor causes the compensatory chaos of renin-angiotensin
      system in mice. It was shown that the concentrations of Angiotensin II in plasma
      and kidney tissues and the expressions of renin and AT1A receptor in the AT2 gene
      null mice were unchanged, as compared with those in AT2 wild-type mice. This
      result suggests that gene deletion of AT2 receptor does not markedly impact the
      stability of renin-angiotensin system and the inductive function of AT2 receptor
      is compensated in a way remaining to be clarified.

PMID- 11324557
TI  - [Co-existence of glutamate and substance P in electrophysiologically identified
      dorsal root ganglion neurons of rats].
AB  - Electrophysiological properties, reaction to substance P (SP) receptor agonist,
      and co-existence of glutamate (Glu) and SP in neurons of the spinal dorsal root
      ganglion (DRG) of the rat were investigated in vitro. The main results were: (1)
      According to the fiber conduction velocity, totally 135 intracellularly recorded
      DRG neurons were divided into A alpha/beta type (> 12 m/s) and C type (< 1.3
      m/s). There were remarkable differences between the fast after hyperpolarization
      (fAHP) of action potential between the two types: fAHP of C type neurons had
      smaller amplititude and longer duration, whereas the fAHP of A alpha/beta type
      neurons had larger amplititude and shorter duration. (2) Among 22 DRG neurons of
      which overshoots of action potential appeared, specific SP receptor agonist Sar
      SP induced depolorization in 42% (5/12) of the A alpha/beta type neurons and 80%
      (8/10) of the C type neurons. (3) Biocytin was intracellularly injected into the
      22 Sar-SP administrated DRG neurons. After fixation and section, employing the
      immunofluorescent histochemical multi-staining technique for phosphate-activated
      glutaminase (PAG, a specific marker for glutamatergic neurons), SP and biocytin,
      25% (3/12) of the A alpha/beta type neurons and 80% (8/10) of the C type neurons
      showed both PAG- and SP-like immunoreactivities. There was a great difference
      between the percentages of the PAG/SP co-existing A alpha/beta type neurons and C
      type neurons (P < 0.05). The present results indicated that there were some
      differences in chemicoanatomical and electrophysiological properties between A
      alpha/beta type and C type neurons, and SP might facilitate the discharge of DRG
      neurons through activating SP autoreceptors on their membrane.

PMID- 11324559
TI  - [Effects of taurine enhancement of synthesis of TxA2 and PGI2 in cultured intra
      pulmonary arteriolar smooth muscle cells under acute hypoxia].
AB  - The results of the present study demonstrated that the concentrations of
      thromboxane B2 (TxB2a) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), and
      their ratio were significantly increased in the medium of intra-pulmonary
      arteriolar smooth muscle cells (PASMCs) under acute hypoxia. Under either
      normoxia or hypoxia the concentration of TxB2 was significantly decreased with
      addition of taurine, while that of 6-keto-PGF1 alpha was significantly increased.
      With the addition of indomethacin, however, under similar conditions, the
      concentrations of both TxB2 and 6-keto-PGF1 alpha were decreased. Furthermore,
      the effect of indomethacin on TxA2 and 6-keto-PGF1 alpha concentrations could be
      reversed by taurine.

PMID- 11324560
TI  - Antagonistic effect of CCK-8 on morphine-inhibited electrical and contractile
      activities of rat jejunum in vitro.
AB  - In the present investigation, antagonistic action of cholecystokinin octapeptide
      (CCK-8) against morphine on the electrical and contractile activity of rat
      jejunum in vitro was studied. The results showed that the potentiation of
      acetylcholine (ACh) on both the burst of spike and the contractility were
      inhibited by morphine, which could be completely antagonized by CCK-8. The CCK-8
      effect, again, could be suppressed by CCK-A receptor antagonist devazepide (10
      nmol/L), but partially by CCK-B receptor antagonist L-365, 260 at 10 nmol/L or
      completely at concentration of 30 nmol/L. The above results demonstrated that the
      antagonism of CCK-8 on morphine was mediated by both CCK-A and CCK-B receptors.

PMID- 11324561
TI  - [A simple method of isolation and identification of P cells in rat sinoatrial
      node].
AB  - A method of isolating P cells of rat sinoatrial node by collagenase is described.
      The method is feasible for morphological and electrophysiological investigation,
      with the advantages of taking a relatively easy procedure and consuming a small
      amount of collagenase. The main features of action potentials of these isolated
      cells including clear diastolic automatic depolarization, mean maximal diastolic
      potential of -55 mV, mean peak potential value of 58 mV, and mean APD50 of 18 ms,
      were similar to those of P cells in situ.

PMID- 11324562
TI  - [Dye coupling between visual cortical (area 17) neurones of adult rat--a study on
      brain slices].
AB  - With intracellular injection of biocytin, forty-nine neurones were successfully
      labeled in in vitro visual cortex (area 17) slices of the adult rat. Out of the
      sample dye coupling was found in 21 cases, for each injection the number of the
      coupled cells varying from 2 to 5 (mean 2.8 +/- 1.1). Eighteen couplings were
      pyramidal-pyramidal, two were pyramidal-nonpyramidal, and one was seen among non
      pyramidal cells. In most cases, the coupled cells were apart from each other with
      a certain distance among their cell bodies (mean 43.1 +/- 24 microns). The
      longest distance was up to 635 microns. Most couplings (19/21) were observed
      within the same lamina; only two in different laminae. The dye couplings were
      found in laminae II/III, IV and V, but mostly in laminae II/III. We have measured
      membrane potential and response properties to white matter and intracellular
      stimulation for the coupled and non-coupled cells; no significant difference was
      found between them.

PMID- 11324563
TI  - [Optokinetic nystagmus (OKN) eye-movement mediated by direct and indirect
      pathways].
AB  - Nasal or temporal side of the cat's retina was stimulated with nasalward and
      temporalward moving patterns for investigating the neural control of the
      optokinetic nystagmus in the direct and indirect pathways of OKN. The
      experimental data demonstrated that there was a nasalward directional preference
      in cat's OKN system under both close loop and open loop conditions, and the
      nasalward OKN gain evoked by stimulation of nasal retina was much higher than
      that at temporal retina. This indicates that OKN nasalward preference is mainly
      derived from the nasal retina, i.e. the direct pathway of OKN dominates the
      indirect pathway in cat's OKN system. The gains of temporalward and nasalward OKN
      from temporal retina are much less than those of nasalward OKN from nasal retina.
      It is suggested that the indirect pathway of OKN in the cat only possesses a
      supplementary function, which probably plays an important role in temporalward
      OKN eye-movements in relation to binocular vision.

PMID- 11324564
TI  - [GABA mediated inhibitory effect of amygdala on the activity of medial geniculate
      body neurons].
AB  - On 10 New Zealand white rabbits immobilized with Flaxedil, the inhibitory effect
      of amygdaloid stimulation on the responses of medial geniculate body (MGB)
      neurons to tone bursts and the involved neurotransmitter mechanism were
      investigated with microiontophoresis technique. The results showed that
      application of GABA could cause a suppression of spontaneous activity of MGB
      neurons while GABAA antagonist bicuculline had an opposite effect. Iontophoretic
      injection of GABA gave an inhibitory effect on MGB neurons similar to that caused
      by stimulating the amygdala or the auditory cortex behind the rhinal sulcus
      (ACBRS), and in particular, the GABA induced suppression could be completely
      antagonized by application of bicuculline. Taken together, these data suggested
      that GABA mediated the amygdaloid inhibitory effect. It seemed unlikely that
      glycine was involved in the effect, since strychnine, a glycine antagonist, could
      not affect the descending inhibition from ACBRS area.

PMID- 11324565
TI  - [Effect of orphanin FQ on acupuncture analgesia and noxious stimulation in the
      periaqueductal gray].
AB  - Orphanin FQ (OFQ) is a newly-discovered neuropeptide which shares great similar
      sequence with endogenous opioid peptide but with different functions. The present
      study was to investigate the role of OFQ microinjected in the periaqueductal gray
      (PAG) on pain threshold and acupuncture analgesia (AA) using tail flick tests.
      The results show that the hyperalgesia of OFQ and its antagonization on AA in PAG
      are dose-related. OFQ in PAG decreases the enhancing effect on AA induced by
      ohmefentanyl, a selective mu-receptor agonist. These observations suggest that
      OFQ in PAG can increase the rat pain sensitivity and antagonize AA.

PMID- 11324566
TI  - [Zinc modulation of GABA receptors expressed in Xenopus oocytes injected with
      carp brain poly(A)+ RNA].
AB  - Two types of GABA receptors, GABAA receptors (approximately 85%) and GABAC-like
      receptors (approximately 15%), were expressed in Xenopus oocytes after injection
      of Poly(A)+ RNA with carp (Carassius carassius) brain. Using voltage-clamp
      technique and pharmacological methods, the effects of zinc on the two receptors
      were studied. It was found that zinc modulation of both GABAA and GABAC-like
      receptors by zinc was inhibitory and reversible with the former being stronger
      than the latter as indicated by a value of IC50 of 48.4 +/- 10.1 mumol/L against
      255.6 +/- 21.5 mumol/L.

PMID- 11324567
TI  - [Peripheral substance P receptor mediating c-fos gene expression in the spinal
      dorsal horn induced by peripheral noxious stimulation].
AB  - Employing immunohistochemical staining for FOS protein, which is the expression
      product of c-fos proto-oncogene, the role of substance P receptor (SPR) in
      noxious information transmission at peripheral terminals of the dorsal root
      ganglion cells was investigated by means of a selective SPR antagonist L668, 169
      and agonist Sar-SP. Unilateral injection of L668, 169 (10(-4) mol/L) into the
      plantar of hindpaw 10 min before injection of 4% formalin, the number of FOS-like
      immunoreactive (LI) neurons in the superficial laminae of dorsal horn was
      significantly decreased, but the changes were not obvious in the deeper laminae.
      Smaller doses of L668, 169 (10(-5), 10(-6) mol/L) were almost ineffective on FOS
      LI neurons in both the superficial and the deeper laminae. However, Sar-SP (10(
      4) mol/L) or formalin did result in the expression of c-fos gene in the
      superficial laminae of the dorsal horn. These results indicated that SP might
      contribute to the transmission of nociceptive information and induce noxious
      sensation, at least in part by activating SPR in peripheral terminals of the
      dorsal root ganglion cells.

PMID- 11324568
TI  - [Inhibition by SKF38393 of GABA-activated currents in rat DRG neurons].
AB  - Experiments were performed on neurons freshly isolated from rat DRG using whole
      cell patch-clamp techniques. The majority of the neurons examined were sensitive
      to GABA (60/70) in the concentration range from 10(-6) to 10(-3) mol/L, showing
      obvious desensitization. In the 60 GABA-sensitive cells, responses induced by
      selective agonist of dopamine D1 receptor SKF38393 [(+/-) SKF38393HCL] manifested
      three types: (1) outward current (7/60); (2) inward current (5/60) and (3) no
      detectable response (48/60). As compared with GABA-activated current, the
      amplitude of SKF38393-activated current are smaller and showed no apparent
      desensitization. When the neurons were treated with SKF38393 prior to application
      of GABA for 30 s, the GABA-activated current in majority of the cells (53/60) was
      inhibited, while the remaining six showed no effect. The effect of SKF38393 was
      dose dependent. That is, with SKF38393 at concentration of 10(-7), 10(-6), 10(-5)
      and 10(-4) mol/L, the GABA-activated current was inhibited by (24.8 +/- 2.6)% (n
      = 7), (26.8 +/- 1.5)% (n = 7), (35.6 +/- 1.2)% (n = 8) and (45.6 +/- 2.3)% (n =
      8) respectively. By intracellular application of 10(-4) mol/L H-7, a potent
      inhibitor of protein kinase, the inhibitory effect of SKF38393 was abolished
      completely, a results suggesting that the inhibition by SKF38393 of the GABA
      activated current might be a result of intracellular phosphorylation of GABAA
      receptor.

PMID- 11324569
TI  - [Neural differentiation of Wnt-1 overexpression P19 cells].
AB  - Wnt-1 gene plays important roles during the development of the mouse central
      neural system. and shown a transient expression during neuronal differentiation
      of P19 EC cells. We transfected Wnt-1 gene into P19 cells and found the Wnt-1
      transfected cells could differentiate into neurons without the induction of RA.
      However, MASH-1, a crucial gene for the early neural differentiation, was
      expressed later than P19 cells induced by RA.

PMID- 11324570
TI  - [Adenosine facilitates carotid baroreflex in rats].
AB  - The effects of adenosine (Ado) on the carotid baroreflex were studied in 27
      anesthetized rats with isolated carotid sinus perfusion. The results obtained
      were as follows: (1) By perfusing the isolated carotid sinus with adenosine (125
      mumol/L), the functional curve of baroreflex was shifted to the left and
      downward, with the peak slope (PS) increased from 0.37 +/- 0.02 to 0.55 +/- 0.02
      kPa/kPa (P < 0.001) and the reflex decrease in mean arterial pressure (RD)
      enhanced from 5.53 +/- 0.12 to 7.76 +/- 0.36 kPa (P < 0.001). Meanwhile, the
      threshold pressure (TP), equilibrium pressure (EP) and saturation pressure (SP)
      were significantly decreased from 8.60 +/- 0.27 to 5.63 +/- 0.11 kPa (P < 0.001),
      12.53 +/- 0.30 to 10.89 +/- 0.29 kPa (P < 0.01) and 23.69 +/- 0.15 to 20.18 +/-
      0.55 kPa (P < 0.001), respectively. Among the functional parameters of carotid
      baroreflex, the changes of RD, PS and TP induced by Ado were dose-dependent. (2)
      By pretreatment with (8-cyclopentyl-1, 3-dipropylxanthine, 0.134 mmol/L), a
      selective adenosine A1-receptor antagonist, the above effects of Ado on carotid
      baroreflex were abolished. (3) The Ado-induced changes of baroreflex were also
      eliminated as the carotid sinus was pretreated with KATP channel blocker
      glibenclamide (10 mumol/L). The results strongly suggest that the carotid
      baroreflex could be facilitated by Ado. It is proposed that the facilitatory
      action of Ado on carotid baroreflex may be resulted from the opening of KATP
      channels mediated by Ado A1-receptors.

PMID- 11324571
TI  - [Dynamic changes of angiotensin II type-1 receptor mRNA expression in volume
      overloaded ventricular hypertrophy].
AB  - Using reverse transcriptase-polymerase chain reaction (RT-PCR) the changes of the
      angiotensin II receptor subtype 1-a (AT1a) and 1-b (AT1b) mRNA levels were
      examined in hypertrophied ventricles caused by ventral aorta-caval fistula of SD
      rats. The results show as follows. (1) Three days after operation, the
      ventricular weight increased significantly, whereas the level of AT1a and AT1b
      mRNA in both ventricles remained unchanged. (2) Twelve days after operation, the
      weight increase of both ventricles was more evident, the levels of AT1a and AT1b
      mRNA in the right ventricle increased (by 62.6% and 72.0%), as compared with
      control. In the left ventricle, on the other hand, the level of AT1a mRNA
      increased by 79.0%, while the level of AT1b mRNA showed no obvious increase. (3)
      Thirty-five days after operation, the levels of AT1a and AT1b mRNA in both
      ventricles increased still more significant, (i.e., 70.0% and 83.9% in the right
      and 96.5% and 86.9% in the left). Moreover, 12 d and 35 d after operation, the
      level of AT1a mRNA was higher than that of AT1b mRNA in both ventricles. (4)
      There was a positive correlation between the degree of ventricular hypertrophy
      with the level of AT1 mRNA in ventricular myocardium (r = 0.6168-0.8223). The
      results suggest that the increased mRNA expression of AT1 in myocardial
      hypertrophy caused by volume overload may be a mechanism underlying the increased
      responsiveness of hypertrophic myocardial cells to Ang II, and a difference in
      the expression between AT1a and AT1b mRNAs in myocardial hypertrophy may be
      related to the different physiological or pathophysiological roles of Ang II,
      mediated by the two subtypes of AT1.

PMID- 11324572
TI  - [The effect of lycium barbarum polysaccharide on vascular tension in two-kidney,
      one clip model of hypertension].
AB  - In the present study, the effects of lycium barbarum polysaccharide (LBP) on
      endothelial function in the two-kidney, one clip model of hypertension were
      observed. The results showed that the increase of blood pressure in hypertension
      rats (HR) could be prevented significantly by treatment with 10% LBP. In isolated
      aortic rings of LBP-treated rats, the contraction of phenylephrine (PE) was
      reduced as compared with HR rats. Removal of the endothelium abolished the
      difference of PE-induced vasoconstriction among groups. In vitro incubation of
      aortic rings from LBP-treated rats with methyl blue (MB) or N-nitro-L-arginine
      methyl ester (L-NAME) increased the magnitude of PE-induced contraction.
      Meanwhile the response to acetylcholine (ACh) was significantly increased in LBP
      treated rats, but the response to nitroprusside had no significant difference
      among groups. Pretreatment with L-arginine partially restored ACh-induced
      relaxation in RH rats, but no effect in LBP-treated rats. These results suggested
      that the role of LBP in decreasing vasoconstriction to PE may be mediated by
      increase of the effects or/and production of endothelium-derived relaxation
      factor (EDRF). LBP increased formation of EDRF may be related to increase the
      substrate of EDRF.

PMID- 11324574
TI  - [GABA initiates the acrosome reaction and fertilizing ability in human sperm].
AB  - The present study was undertaken to investigate whether GABA induced the acrosome
      reaction (AR) and fertilizing ability, as well as its possible mode of action in
      human spermatozoa. Spermatozoa from fifteen health fertile men isolated by the
      swim-up technique were preincubated in a modified BWW with 0.35% BSA for 1-11 h
      under 5% CO2 in 95% air at 37 degrees C. Aliquots of spermatozoa were collected
      at 0, 1, 3, 5, 7, 9 and 11 h of incubation for evaluation of the AR by
      chlortetracycline (CTC) staining. The sperm penetration assay (SPA) was carried
      out by using the zona-free hamster oocyte test. Intracellular calcium ([Ca2+]i)
      concentrations were determined by means of fluorescent probe Frua-2/AM. GABA at
      1.25 mumol/L significantly induced the AR in human spermatozoa preincubated for 3
      h, with a maximal response in preincubated for 9 h, and the effect changed in a
      concentration-dependent manner. The maximal stimulatory effect was observed with
      1.25 mumol/L GABA, and the AR then decreased markedly with further increase of
      GABA concentration to 10 mumol/L. Exposure of preincubated spermatozoa to GABA in
      combination with progesterone resulted in a higher proportion of the AR as
      compared with that obtained with each agonist applied alone. In addition, GABA
      prompted a rapid increase in interacellular [Ca2+]i. Furthermore, the AR induced
      by GABA was prevented by inclusion of 1 mmol/L EGTA or 100 mumol/L La3+. Also,
      GABA enhanced significantly the ability of spermatozoa penetrating zona-free
      hamster oocytes and the index of fertilization. These results indicate that GABA
      may be involved in the modulation of the AR and the fertilization process in
      capacitated human spermatozoa through a calcium mediated mechanism, thus opening
      up possibilities for studies of signal transductions through activation of the
      GABAA receptor present on the sperm surface.

PMID- 11324573
TI  - [An animal experiment and clinical investigation on the protective effect of
      selenium on the microcirculation induced by free radical damaged RBCs].
AB  - Fluorescent labeling image analysis was used to evaluate the changes in cerebral
      arteriole and veinlet diameters (D), circulation velocities (FV) and permeability
      (VP) in rats; while in clinics, a laser-doppler device was used for assessing
      changes of skins and muscles microcirculation. The results show that in control
      rats, equal volume perfusion of free radical damaged RBCs resulted in decreases
      of D and FV significantly but VP was increased, whereas in the case when free
      radical damaged RBCs were perfused together with selenium, no disturbances in the
      D and VP were observed with FV even improved. In the human control group, either
      average skin microcirculative perfusions (ASMP) at 25 degrees C or maximal skin
      microcirculative perfusions (MSMP) at 42 degrees C were evidently decreased
      during myocardial ischemia/reperfusion period, while ASMP at 24th hour of post
      surgery was kept reducing. At the same time, the changes in muscles
      microcirculative perfusions (MMP) tended to be similar to the skin, but
      overloaded than the pre-surgery levels at 24th hour of post-surgery period. In
      the selenium group before surgery, the ratio of MSMP to ASMP was obviously
      increased than the control group (3.95 in Se group vs 1.74 in control group, P <
      0.05), but did not have significantly differences in ASMP, MSMP and MMP between
      the two groups during surgery period. RBC deformabilities were not changed. At
      24th hour post-surgery, the ASMP were almost restored to pre-surgery levels.
      However, MMP were still lower than the pre-surgery levels. CONCLUSIONS: (1) free
      radical damaged RBC perfusion leads to damage of microcirculation; (2) selenium
      is highly efficient in protecting microcirculation from free radical damaged RBC
      disturbance; and (3) Oral administration of selenium may improve pre-surgery
      maximal skin microcirculative perfusion and promote recovery of the worsened skin
      microcirculation in addition to prevent the occurrence of RBC deformability.

PMID- 11324575
TI  - [Modulation of endothelin-1 on pulmonary surfactant secretion].
AB  - The effects of endothelin-1 (ET-1) at physiological level on the secretion of
      pulmonary surfactant (PS) were studied on isolated nonperfused rat lungs. The
      results showed that ET-1 (10(-12) and 10(-10) mol/L) increased the basal
      secretion of total phospholipids (TP) and phosphatidylcholine (PC), and
      potentiated the stimulatory effect of intermittent lung inflation on the
      secretion of TP and PC. The effect of ET-1 could be inhibited by H7, a protein
      kinase C (PKC) inhibitor. When the cultured lung tissue was exposed respectively
      to ET-1 (10(-12) and 10(-10) mol/L) for 1 h and 4 h, the content of ET in the
      lung tissue increased significantly. These results suggest that ET-1 at the
      physiological concentration is involved in modulating PS secretion through a PKC
      dependent pathway, and can also promote ET production in lungs.

PMID- 11324576
TI  - [Comparison of NMDA and non-NMDA receptor antagonists-induced inhibition in
      hindpaw withdrawal response to noxious thermal stimulation].
AB  - In our previous electrophysiological study, it was shown that NMDA receptors are
      predominantely involved in the transmission of nociceptive cutaneous afferents,
      whereas non-NMDA receptors are mainly concerned with the transmission of
      nociceptive muscular afferents. In the present investigation, the effects of NMDA
      and non-NMDA receptor antagonists were tested in rat hindpaw withdrawal response
      to noxious thermal stimulation. Intrathecal application of non-NMDA receptor
      antagonist 1 nmol/L DNQX (6,7-dinitroquinoxaline-2,3(1H, 4H)-dione) had no effect
      on paw withdrawal latencies (PWL), but NMDA receptor antagonist 1 nmol/L APV [(+/
      ) 2-amino-5-phosphonovalerate)] significantly prolonged PWL (P < 0.05). Both APV
      and DNQX at 10 nmol/L significantly increased PWL with the former agent being
      more potent. The results further support that both NMDA and non-NMDA receptors
      are involved in the transmission of spinal nociception, with the former being
      more preferentially involved in the transmission of nociceptive information from
      the skin.

PMID- 11324577
TI  - [Heat shock response induces resistance to hydrogen peroxide and increases
      synthesis of interleukin-6 in rat astrocyte in vitro].
AB  - Cell viability and cell membrane disruption of rat astrocyte after heat shock
      response (HSR) were assessed by the analysis of MTT reduction and lactate
      dehydrogenase (LDH) release. We studied whether HSR would modulate the
      susceptibility of astrocyte to H2O2-induced oxidative stress. Cell viability was
      assessed by reduction of MTT. HSR in 43 degrees C water bath for 30 min decreased
      H2O2 toxicity (P < 0.01) to astrocyte. HSR induced decrease in H2O2 (50 mumol/L)
      toxicity was also shown by the reduction in the release of LDH, which was a
      marker of cell membrane disruption. The result also showed that prior to the
      incubation in 43 degrees C water bath for 30 min strongly increased IL-6 release
      6 h (P < 0.05) after HSR. The above data suggest that the enhanced release of IL
      6 from astrocyte may be one of the mechanisms underlying the cell protective
      effect induced by HSR.

PMID- 11324578
TI  - [The stimulation of glutamate uptake by the phorbol ester in rat cerebral cortex
      synaptosomes and cell line of human anaplastic astrocytoma BT-325].
AB  - The effects of protein kinase C (PKC) and protein kinase A (PKA) on the high
      affinity glutamate uptake in rat cerebral cortex synaptosomes, cell lines of
      human neuroblastoma SK-N-SH and human anaplastic astrocytoma BT-325 were studied
      by measurement of radioactivity of 3[H]-L-glutamate. The results were as follows:
      (1) PKC agonist phorbol-12-myristate, 13-acetate (PMA) stimulated the glutamate
      uptake in the rat cerebral cortex synaptosomes and cell line of BT-325, but not
      in the cell line of SK-N-SH. This effect of PMA was abolished in the presence of
      PKC antagonist sphingosine. (2) Glutamate uptake in all these three samples of
      neural tissues and cells was not affected by PKA agonist adenosine 3',5'
      cyclicmonophosphate, N6,O2'-dibutyryl. The above results indicate that it is PKC
      that stimulates high affinity glutamate uptake in glial cells, although the
      possibility that neurons are also affected to some extent can not be ruled out.

PMID- 11324579
TI  - [Pathways of signal transduction of intracellular Ca2+ increase mediated by three
      subtypes of alpha 1-adrenoceptor in HEK293 cells].
AB  - In HEK293 cell lines in which alpha 1a-, alpha 1b- or alpha 1d-adrenoceptor
      subtypes were stably expressed, fluorescence intensities due to traces of Ca2+
      were investigated using fura-2/AM with the aim of exploring signal transduction
      pathways of intracellular Ca2+ increase mediated by these receptor subtypes.
      Pertussis toxin had no effect on [Ca2+]i increase mediated by all three subtypes
      of alpha 1-adrenoceptors. However, U-73122 and PMA could inhibited the [Ca2+]i
      increase induced by NE, which was not affected by Foskolin and Rp-cAMPs.
      Pretreatment with calphostin C abolished the [Ca2+]i response to PMA. Quercetin
      and tyrphostin inhibited maximal [Ca2+]i increase but had no effect on the
      plateau phase in all the three transfected cells. In the HEK293 cells, the
      phosphatide-Ca2+ signalling system mediated by the 3 subtypes of alpha 1-AR was
      brought into play by activation of phospholiphase C via coupling with PTX
      insensitive G proteins. PKC system inhibited both mobilization of internal Ca2+
      stores and the Ca2+ influx across the plasma membrane. Tyrosine kinase, but not
      cAMP system, might participate in such Ca2+ signalling.

PMID- 11324580
TI  - [Changes of intracellular calcium level in hippocampal slice neurons: a confocal
      laser scanning microscopic study].
AB  - In this study, the fluorescent dye Fluo-3 (AM) was applied to rat hippocampus by
      microinjection, to label neurons in situ. A large number of CA1 pyramidal cells
      could be labeled by a single injection. With this improvement of labeling and the
      use of the confocal laser scanning microscope (Leica Lasetechnik GmbH), changes
      of calcium fluorescence intensity in CA1 pyramidal cells of rat hippocampal
      slices on the models of mimic epilepsy (induced by penicillin or glutamate) or
      hypoglycemia/hypoxia were studied in vitro. The results showed that in magnesium
      free artificial CSF, the intracellular calcium level of the CA1 pyramidal cells
      increased following application of glutamate or penicillin. Similar phenomenon
      was also observed on the in vitro model to hypoglycemia/hypoxia.

PMID- 11324581
TI  - Delta and notch promote correct localization of irreC-rst.

PMID- 11324582
TI  - Re: a home program of rehabilitation for moderately severe traumatic brain injury
      patients.

PMID- 11324583
TI  - Bibliography. Current world literature. Renal medicine and renal transplantation.

PMID- 11324584
TI  - Bibliography. Current world literature. Imaging: new diagnostic techniques.

PMID- 11324585
TI  - Interruption of siaD in a meningococcal carrier isolate mediated by an insertion
      sequence.

PMID- 11324586
TI  - Impact of initial screening for human T-cell lymphotropic virus (HTLV) antibodies
      on efficiency of HTLV Western blotting.

PMID- 11324588
TI  - Allele frequency distribution for four VNTR loci in the Chinese Han population.

PMID- 11324587
TI  - Effectiveness of remune.

PMID- 11324589
TI  - Allele frequency for three STR loci in a population sample from Catalonia (Spain)
      using a simple manual triplex PCR method.

PMID- 11324590
TI  - Distribution of HumHPRTB and HumF13A01 alleles in Buenos Aires Population
      (Argentina).

PMID- 11324591
TI  - Filobacillus milensis gen. nov., sp. nov., a new halophilic spore-forming
      bacterium with Orn-D-Glu-type peptidoglycan.
AB  - A spore-forming, halophilic bacterium was isolated from surface sediment located
      on the beach of Palaeochori Bay near to a shallow water hydrothermal vent area,
      Milos, Greece. The bacterium, designated SH 714T, consisted of motile, strictly
      aerobic rods which contained an Orn-D-Glu type murein and a G+C content of 35
      mol%. Thin sections showed a cell wall typical for Gram-positive bacteria; the
      peptidoglycan layer, however, was very thin. The Gram-reaction of the organism
      was negative. Comparative 16S rRNA gene sequencing demonstrated that the isolate
      represents a new line of descent within the spore-forming rods branching at the
      periphery of the rRNA group 1 Bacillus (Bacillus sensu stricto). The nearest
      phylogenetic neighbours of the unknown bacterium were Bacillus haloalkaliphilus,
      Marinococcus albus and Halobacillus species. Based on phylogenetic and phenotypic
      evidence it is proposed that the unknown bacterium be classified as Filobacillus
      milensis gen. nov., sp. nov. The type strain is SH 714T (= DSM 13259T = ATCC
      700960T).

PMID- 11324592
TI  - Comparison of methods for extraction of tobacco alkaloids.
AB  - Ultrasound and microwave techniques were used to extract tobacco alkaloids, and
      response surface methodology was used to optimize extraction conditions.
      Ultrasonic technique factors were temperature, 30-85 degrees C; time, 3-45 min;
      solvent volume, 8-80 mL. Microwave extraction factors were pressure, 15-75 psi;
      time, 3-40 min; power, 30-90% of the maximum magnetron power of 650 W. Soxhlet
      and solvent AOAC-modified extraction methods were also applied after some
      improvements. Nicotine, nornicotine, anabasine, and anatabine were quantified by
      gas chromatography. A steam distillation International Standards Organization
      method for total alkaloid evaluation was used as reference. The results obtained
      by the different methods were compared using a least squares deviation test. The
      ultrasonic and the proposed modified-AOAC extraction method were the more
      convenient with regard to practicability and precision. The relative deviations
      (n = 5) were as follows: For the ultrasonic method in low-level alkaloid
      tobaccos, 0.7% nicotine and 1.4-14% minor alkaloids; in high-level alkaloid
      tobaccos, 2.4% nicotine and 4.5-5.1% minor alkaloids. For the modified AOAC
      method in low-level alkaloid tobaccos, 0.9% nicotine and 2.4-11.6% minor
      alkaloids; and in high-level alkaloid tobaccos, 1.7% nicotine and 2.0-2.4% minor
      alkaloids.

PMID- 11324593
TI  - Determination of acetochlor in technical and formulated products by capillary gas
      chromatography: PVM 5:1999.
AB  - A peer-verified gas chromatographic (GC) method is presented for the weight
      percent (wt %) determination of acetochlor herbicide in technical and formulated
      products. During method development, the method was found to be rugged by the
      Youden Ruggedness Test. Two laboratories with experience in the wt %
      determination of acetochlor in various matrixes participated in this study. Each
      laboratory received 10 blind duplicate test samples of the following 5 matrixes:
      one acetochlor technical and 4, different, emulsifiable concentrate (EC)
      formulations--Harness EC (MON 5841), Harness Export/Fist (MON 8435), Surpass EC
      (HF), and Surpass EC (LF). Each participant was asked to make duplicate weighings
      of each of the test samples and to inject each test sample solution twice. All
      test samples were analyzed on the same day, and 8 data points (replicates) per
      matrix were obtained. The test samples were dissolved in acetone that contained
      dipentyl phthalate as an internal standard. They were analyzed by GC on a 15 m
      capillary column by using split injection and a flame ionization detector.
      Acetochlor (wt %) was determined by comparing the ratios of peak area of
      acetochlor/peak area of dipentyl phthalate internal standard obtained for the
      test sample and calibration solutions. Repeatability of the method, expressed as
      the within-laboratory (between replicates) relative standard deviation (RSDr),
      was found to be 0.09-0.77% for the 5 matrixes. Reproducibility of the method,
      expressed as the within-test sample relative standard deviation (RSDR), was found
      to be 0.18-0.78% for the

PMID- 11324594
TI  - Analytical study of comprehensive and targeted multidimensional gas
      chromatography incorporating modulated cryogenic trapping.
AB  - This paper reports the results of an analytical study comparing capillary gas
      chromatography (GC) operated in the normal mode with 2 new GC techniques,
      comprehensive GC (GC x GC) and targeted (or selective) multidimensional GC, which
      use a longitudinally modulated cryogenic system (LMCS), recently developed in our
      laboratory. A high-temperature application of derivatized sterols, of interest in
      fecal pollution monitoring, was chosen for this work. A directly connected
      coupled-column ensemble was used, comprising a nonpolar column and a moderately
      polar column. With LMCS, effluent from the first column is zone-compressed in a
      cryogenic trap and then pulsed to a short second column, producing narrower peaks
      with sharp, tall peak responses at the detector. The modulator is operated at a
      constant frequency, e.g., 0.25 s(-1), to produce the GC x GC result, or is moved
      in a predefined manner so that whole peaks are selectively trapped and
      subsequently pulsed through to the second column in the targeted mode. Standard
      solutions containing a mixture of 7 sterols and 5-alpha-cholestane internal
      standard were used. Detection sensitivity is increased by a factor of >25 with
      the use of LMCS. The estimated limit of detection was about 0.1 microg/mL when
      normal GC with flame ionization detection (GC/FID) and a 1.0 microL splitless
      injection volume were used, compared with 0.02 and 0.004 microg/mL for the LMCS
      operated in GC x GC and selective modes, respectively. Calibration curves for
      GC/FID were linear over the 0.1-2.0 microg/mL range tested. Reproducibilities for
      the GC x GC and normal GC modes were comparable; generally, relative standard
      deviations (RSD) were on the order of 3-4%, based on raw peak responses. Improved
      reproducibility was found for selective LMCS operation, at an RSD of around 2%;
      with internal standardization, better results were achieved. The coupled-column
      arrangement allowed complete separation of sterol peaks from overlapping impurity
      peaks in a number of instances with LMCS modes, and its use should improve data
      quality over that of normal GC operation, in which the overlapping peaks
      interfere with measurement of peak response in the normal mode.

PMID- 11324595
TI  - Sequential-injection procedure for determination of iodide in pharmaceutical and
      drinking water samples by catalytic reaction with spectrophotometric detection.
AB  - A novel sequential-injection system was developed for determination of iodide at
      very low concentrations by using a kinetic method. The method is based on the
      catalytic effect of iodide on the redox reaction between Ce4+ and As3+ first
      described by Sandell and Kolthoff. The calibration curve is constructed by
      measuring the decrease of Ce4+ absorbance versus iodide concentration with a
      delay time of 30 s. The detection limit is 1.5 microg/L, the working temperature
      is 45 degrees C, and the working range is 0.002-0.5 mg/L. Reasonable agreement
      was obtained when the method was applied to pharmaceutical and drinking water
      samples. The method has a sample throughput of approximately 15/h.

PMID- 11324596
TI  - New method for determination of ten pesticides in human blood.
AB  - An analytical method was developed for precise identification and quantitation of
      10 pesticides in human blood. The pesticides studied, which have appeared
      frequently in actual cases, were endosulfan, lindane, parathion, ethyl-azinphos,
      diazinon, malathion, alachlor, tetradifon, fenthion and dicofol (o-p' and p-p'
      isomers). The current method replaces an earlier method which involved liquid
      liquid extraction with a mixture of n-hexane-benzene (1 + 1). The extraction is
      performed by solid-phase extraction, with C18 cartridges and 2 internal
      standards, perthane and triphenylphosphate. Eluates were analyzed by gas
      chromatography (GC) with nitrogen-phosphorus and electrochemical detectors.
      Results were confirmed by GC-mass spectrometry in the electron impact mode. Blood
      blank samples spiked with 2 standard mixtures and an internal standard were used
      for quantitation. Mean recoveries ranged from 71.83 to 97.10%. Detection and
      quantitation limits are reported for each pesticide. Examples are provided to
      show the application of the present method to actual samples.

PMID- 11324597
TI  - Survey of residual tetracyclines in kidneys of diseased animals in Aichi
      Prefecture, Japan (1985-1997).
AB  - A survey was conducted to determine the incidence of tetracycline antibiotic
      (TCAs) residues in the kidneys of slaughtered animals that did not pass
      inspection for human consumption by the Japanese Food Sanitation Law and the Meat
      Inspection Law at the slaughterhouses in Aichi Prefecture, Japan, from April 1985
      to March 1998. The kidneys were analyzed by the AOAC Official Method 995.09.
      Among 424 animals (147 cattle and 277 pigs), 131 (30.9%) were contaminated with
      TCAs, including 69 (16.3%) with chlortetracycline (CTC), 61 (14.4%) with
      oxytetracycline (OTC), 3 (0.7%) with tetracycline (TC), and 1 (0.2%) with
      doxycycline (DC). One sample (cattle kidney) was contaminated with both OTC and
      DC. The frequencies of OTC and TC residues were significantly higher (p < 0.05)
      in cattle than in pigs, whereas, the frequency of CTC was significantly higher (p
      < 0.01) in pigs. Pig kidney samples collected in 1991-1997 had significantly
      higher incidences of TCAs and CTC (p < 0.01) residues than those in 1985-1986.

PMID- 11324598
TI  - Simultaneous determination of all-trans-retinoic acid, beta-carotene, and vitamin
      A in galenic preparations by liquid chromatography.
AB  - The concentrations of vitamin A, beta-carotene, and all-trans-retinoic acid in
      oral preparations were determined in a single analysis by a method based on
      isocratic, reversed-phase liquid chromatography (LC). The LC system consisted of
      a C18 column, a mobile phase of acetonitrile, dichloromethane, methanol, and
      water and a UV detector set at 330 nm. The linearity ranges were 25-250 ng/mL for
      trans-retinoic acid and vitamin A, and 100-1,000 ng/mL for beta-carotene. This LC
      method for the determination of retinoids is simple, precise, and accurate. No
      extraction procedure is required before the chromatographic analysis; only a
      suitable dilution is necessary. The method proved to be reliable, fast, and
      economical. Furthermore, this method is indicative of stability, because it
      allows for the determination of degradation products such as 13-cis-retinoic
      acid.

PMID- 11324599
TI  - Comparison of three analytical methods for quality control of clozapine tablets.
AB  - Three different analytical methods for the quality control of clozapine in
      commercial formulations were developed and compared: a liquid chromatographic
      (LC) method with UV detection, a capillary zone electrophoretic (CZE) method, and
      a linear scan voltammetric (LSV) method. The isocratic LC procedure used a C18
      reversed-phase column; the CZE method used an uncoated fused-silica capillary and
      phosphate buffer containing polyvinylpyrrolidone as the background electrolyte;
      the LSV method analyzed clozapine solutions with acidic phosphate buffer as the
      supporting electrolyte. The 3 methods gave similar and satisfactory results, in
      terms of precision and accuracy. Repeatability and intermediate precision were
      good (RSD% < 2.2) and accuracy, resulting from recovery studies, was between 98
      and 102%. The rapidity of analysis was high for all 3 methods, especially for the
      LSV.

PMID- 11324600
TI  - Derivative spectrophotometric analysis of 4-quinolone antibacterials in
      formulations and spiked biological fluids by their Cu(II) complexes.
AB  - A derivative UV-spectrophotometric analytical procedure was developed for
      determination of three 4-quinolone antibacterials: norfloxacin (NFX),
      ciprofloxacin (CFX), and sparfloxacin (SFX). The method depends on the
      complexation of Cu(II) with the studied compounds in aqueous medium. A third
      order, measurement was applied for their quantification. A linear correlation was
      established between the amplitude of the peak and concentration for all the
      studied drugs in the range of 15-80, 35-120, and 200-700 ng/mL, with minimum
      detectability (S/N = 2) of 1.0, 1.3, and 5.1 ng/mL for NFX, CFX, and SFX,
      respectively. The method was successfully applied for accurate, sensitive, and
      selective determination of the studied drugs in bulk and tablets formulation with
      average percentage recoveries of 99.22 +/- 0.55 to 100.33 +/- 1.60. The results
      obtained were favorably compared with those of the reference method. The method
      was also used to determine sparfloxacin in spiked human plasma and urine. The
      results obtained were satisfactory, accurate, and precise.

PMID- 11324601
TI  - Determination of musk ambrette, musk xylol, and musk ketone in fragrance products
      by capillary gas chromatography with electron capture detection.
AB  - A gas chromatographic method using a capillary column with electron capture
      detection was developed for the simultaneous determination of 3 nitromusk
      fragrance ingredients: musk ambrette (MA), musk xylol (MX), and musk ketone (MK),
      in fragrance products. The accuracy of the method was determined by recovery of
      each nitromusk from fortified fragrance products at 3 different concentrations.
      Recoveries ranged from 95.0 to 105.9% for MA, 88.4 to 102.5% for MX, and 93.7 to
      103.7% for MK. The method was used to survey 30 fragrance products purchased in
      the Washington, DC, area for each of the nitromusks. MA was not found in any of
      the products. MX was found in 9 products at levels ranging from 0.001 to 0.22%;
      MK was found in 8 products at levels ranging from 0.023 to 0.45%. The presence of
      MX and MK was confirmed by gas chromatography/mass spectrometry in many of the
      fragrance products.

PMID- 11324602
TI  - Determination of phthalates in crude extracts of sewage sludges by high
      resolution capillary gas chromatography with mass spectrometric detection.
AB  - A simple solvent extraction by ethyl acetate without subsequent cleanup was used
      to determine 16 phthalic acid esters (PAEs), including bis(2-ethylhexyl)
      phthalate (DEHP), in sewage sludge samples from different catchment areas. The
      compounds were separated on a gas chromatographic capillary column with a
      nonpolar HT-8 stationary phase. For most of the PAEs, internal standard
      quantification with deuterated dibutyl phthalate (DBP) and deuterated DEHP was
      best achieved by using electron ionization mass spectrometry in the selected-ion
      monitoring mode. Because of its high concentrations in the sludges, DEHP was
      quantified in the full-scan acquisition mode. Molecular weight and ester-type
      information for the PAEs was obtained in the positive chemical ionization mode
      with methane as the reagent gas. Finally, selected sewage sludges containing
      different amounts of industrial wastewater were analyzed by the proposed method.
      DEHP was the most abundant compound found at 21-114 mg/kg x dm, followed by the
      lower-molecular weight PAEs diethyl phthalate, diisobutyl phthalate, and DBP and
      the higher-molecular weight compounds butylbenzyl phthalate, dicyclohexyl
      phthalate, di-n-octyl phthalate, and dinonyl phthalate, which were present mostly
      at <1 mg/kg x dm.

PMID- 11324603
TI  - Determination of 3-trifluoromethyl-4-nitrophenol and 3-trifluoromethyl-4
      nitrophenol glucuronide in edible fillet tissue of rainbow trout and channel
      catfish by solid-phase extraction and liquid chromatography.
AB  - 3-Trifluoromethyl-4-nitrophenol (TFM) is a pesticide used for the selective
      control of sea lampreys (Petromyzon marinus) in stream and river tributaries of
      the Great Lakes. To determine concentrations of TFM and TFM glucuronide in the
      edible fillet tissue of fish during sea lamprey control treatments, an analytical
      method was developed to determine the concentrations of these residues in rainbow
      trout (Oncorhynchus mykiss; RBT) and channel catfish (Ictalurus punctatis; CCF).
      Homogenized fillets were extracted with methanol-water (80 + 20). TFM and TFM
      glucuronide were isolated from coextractives by C18 solid-phase extraction. TFM
      glucuronide was hydrolyzed to TFM by the addition of beta-glucuronidase to the
      TFM glucuronide extract. The extracts were analyzed separately by liquid
      chromatography with UV-visible detection. Recoveries from TFM-fortified CCF and
      RBT tissues were 84.1 and 96.1%, respectively. The method detection limits (MDLs)
      are 2.4 ng/g for TFM-fortified tissues of CCF and 3 ng/g for those of RBT.
      Recoveries were 78.8 and 77% from TFM glucuronide-fortified CCF and RBT tissues,
      respectively. The MDLs for TFM glucuronide-fortified tissues are 3.5 and 6.9 ng/g
      for CCF and RBT, respectively.

PMID- 11324604
TI  - Visible spectrophotometric determination of tantalum in soil, sediment, minerals,
      and alloys.
AB  - A new, sensitive, and selective method is described for the spectrophotometric
      determination of Ta(V). The method is based on the extraction of the Ta(V)-F-CV+
      complex (CV+ = crystal violet cation) with a benzene solution of imidoyl
      derivatives (ID), i.e., N,N'-diphenylbenzamidine (DPBA), N-hydroxy-N,N'
      diphenylbenzamidine, and N-(2,5-dimethyl)phenyl-p-tolylimidoylphenylhydrazine,
      from sulfuric acid solution; DPBA was selected for detailed study. The molar
      absorptivities of the Ta(V)-F-CV+-ID complexes in the benzene solution were in
      the range of (1.00-1.65) x 10(5) L/mol x cm at 600 nm. The limit of detection was
      7 ng Ta/mL (which had an absorbance greater than that of the blank + 3 standard
      deviations). The optimization of the analytical variables, the composition of the
      complex, and the effect of diverse ions in the determination of Ta are discussed.
      The present method was applied to the determination of Ta in environmental
      samples, i.e., soil, sediment, minerals, and alloys.

PMID- 11324605
TI  - Rapid methods to enumerate Escherichia coli in foods using 4-methylumbelliferyl
      beta-D-glucuronide.
AB  - Three methods to enumerate Escherichia coli in food were compared. They were
      based on AOAC methods using lauryl tryptose broth (LST) medium, LST-4
      methylumbelliferyl-beta-D-glucuronide (MUG) medium, and a proposed method using
      regular LST in combination with E. coli (EC)-MUG medium. An efficacious and cost
      effective method is needed that can detect E. coli and does not produce false
      presumptive positives. We tested 170 cheeses, 40 frozen processed seafood
      samples, 210 tree nuts, and 40 other samples. The method of choice for
      enumerating E. coli depends on the commodity itself. For a product, such as hard
      cheese or processed seafood, with a history of being negative for E. coli and
      other lactose-fermenting organisms, the proposed method using regular LST/EC-MUG
      is a good choice. These samples were seldom presumptive positive in the primary
      LST medium. If gas was produced, EC-MUG was an effective secondary medium. No
      false positives (fluorescence) or negatives were detected in EC-MUG medium. For a
      product with a history of being positive for E. coli and/or other lactose
      fermenting organisms, such as tree nutmeats or cheeses that are ripened by
      bacteria or mold, the method using LST-MUG is the method of choice. A presumptive
      positive in the LST-MUG medium was highly correlative with the biochemical tests
      that confirmed a sample contain E. coli. For samples spiked with E. coli, the
      results from each of these 3 methods were identical, and were consistent in
      enumerating E. coli.

PMID- 11324606
TI  - TECRA Unique test for rapid detection of Salmonella in food: collaborative study.
AB  - The TECRA Unique Salmonella test uses the principle of immunoenrichment to allow
      rapid detection of Salmonellae in food. A collaborative study was conducted to
      compare the TECRA Salmonella Unique test with the reference culture method given
      in the U.S. Food and Drug Administration's Bacteriological Analytical Manual.
      Three food types (milk powder, pepper, and soy flour) were analyzed in Australia
      and 2 food types (milk chocolate and dried egg) were analyzed in the United
      States. Forty-one collaborators participated in the study. For each of the 5
      foods at each of the 3 levels, a comparison showed no significant differences (p
      > or = 0.05) in the proportion of positive test samples for Unique and that for
      the reference method using the Chi-square test for independence with continuity
      correction.

PMID- 11324607
TI  - Determination of plastic monomers in water by solid-phase microextraction coupled
      with liquid chromatography.
AB  - A method is presented for the determination of 2 major plastic monomers,
      terephthalic acid and vinyl acetate, which are widely used to manufacture
      plastics that come in contact with foods. The analytes are extracted from aqueous
      solution by using solid-phase microextraction, followed by quantitation by liquid
      chromatography (LC) with UV detection. Multivariate optimization was applied and
      is described. The optimized method has linear ranges of 5-150 microg/g for
      terephthalic acid and 7.5-100 microg/g for vinyl acetate. Coefficients of
      variation at a spiking level of 20 microg/g were 13.6% for terephthalic acid and
      3.1% for vinyl acetate; detection and quantitation limits were 0.59 and 1,99
      microg/g, respectively, for terephthalic acid and 1.56 and 5.20 microg/g,
      respectively, for vinyl acetate. The characteristics of both the extraction
      technique and its coupling with LC are described and discussed.

PMID- 11324608
TI  - Immunoaffinity column cleanup with liquid chromatography for determination of
      aflatoxin M1 in liquid milk: collaborative study.
AB  - A collaborative study was conducted to evaluate the effectiveness of an
      immunoaffinity column cleanup liquid chromatographic method for determination of
      aflatoxin M1 in milk at proposed European regulatory limits. The test portion of
      liquid milk was centrifuged, filtered, and applied to an immunoaffinity column.
      The column was washed with water, and aflatoxin was eluted with pure
      acetonitrile. Aflatoxin M1 was separated by reversed-phase liquid chromatography
      (LC) with fluorescence detection. Frozen liquid milk samples both naturally
      contaminated with aflatoxin M1 and blank samples for spiking, were sent to 12
      collaborators in 12 different European countries. Test portions of samples were
      spiked at 0.05 ng aflatoxin M1 per mL. After removal of 2 noncompliant sets of
      results, the mean recovery of aflatoxin M1 was 74%. Based on results for spiked
      samples (blind pairs at 1 level) and naturally contaminated samples (blind pairs
      at 3 levels) the relative standard deviation for repeatability (RSDr) ranged from
      8 to 18%. The relative standard deviation for reproducibility (RSDR) ranged from
      21 to 31%. The method showed acceptable within- and between-laboratory precision
      data for liquid milk, as evidenced by HORRAT values at the low level of aflatoxin
      M1 contamination.

PMID- 11324609
TI  - Combined phenyl silane and immunoaffinity column cleanup with liquid
      chromatography for determination of ochratoxin A in roasted coffee: collaborative
      study.
AB  - A collaborative study was conducted to evaluate a liquid chromatography (LC)
      method for ochratoxin A using sequential phenyl silane and immunoaffinity column
      cleanup. The method was tested at 3 different levels of ochratoxin A in roasted
      coffee, which spanned the range of possible future European regulatory limits.
      The test portion was extracted with methanol and sodium bicarbonate by shaking
      for 30 min. The extract was filtered, centrifuged, and then cleaned up on a
      phenyl silane column before being eluted from the washed column with methanol
      water. The eluate was diluted with phosphate-buffered saline (PBS) and applied to
      an ochratoxin A immunoaffinity column, which was washed with water. The
      ochratoxin A was eluted with methanol, the solvent was evaporated, and the
      residue was redissolved in injection solvent. After injection of this solution
      onto a reversed-phase LC apparatus, ochratoxin A was measured by fluorescence
      detection. Eight laboratory samples of low-level naturally contaminated roasted
      coffee and 2 laboratory samples of blank coffee (< 0.2 ng/g ochratoxin A at the
      signal-to-noise ratio of 3:1), along with ampules of ochratoxin A calibrant and
      spiking solutions, were sent to 15 laboratories in 13 different European
      countries. Test portions of the laboratory samples were spiked at levels of 4
      ng/g ochratoxin A, and recoveries ranged from 65 to 97%. Based on results for
      spiked blank material (blind duplicates) and naturally contaminated material
      (blind duplicates at 3 levels), the relative standard deviation for repeatability
      (RSDr) ranged from 2 to 22% and the relative standard deviation for
      reproducibility (RSDR) ranged from 14 to 26%. The method showed acceptable within
      and between-laboratory precision, as evidenced by HORRAT values, at the low
      level of determination for ochratoxin A in roasted coffee.

PMID- 11324610
TI  - Isoflavone glycosides from the root wood of Erythrina latissima.
AB  - The molecular structures of 3 isoflavone glycosides isolated from the root wood
      of Erythrina latissima were established as 4'-hydroxyisoflavone-7-O-beta-D
      glucopyranoside (compound 1); 4'-hydroxyisoflavone-7-O-alpha-L-rhamnosyl (1-->6)
      beta-D-glucopyranoside (compound 2); and a new compound 4', 8-dimethoxy
      isoflavone-7-O-alpha-L-rhamnosyl (1-->6) glucopyranoside (8-O-methylretusin-7-O
      alpha-L-rhamnosyl (1-6)-beta-D-glucopyranoside) (compound 3).

PMID- 11324611
TI  - Determination of 3-chloro-1,2-propanediol in foods and food ingredients by gas
      chromatography with mass spectrometric detection: collaborative study.
AB  - The results of a collaborative study are reported for the determination of 3
      chloro-1,2-propanediol (3-monochloropropane-1,2-diol; 3-MCPD) in a wide range of
      foods and food ingredients, using gas chromatography with mass spectrometric
      detection and incorporating the use of a deuterated internal standard. After a
      pretrial study, 12 laboratories (6 United Kingdom, 1 Switzerland, 1 Japan, 2
      United States, 1 The Netherlands, and 1 from the European Commission) were asked
      to analyze 12 test materials (as known duplicates or split-level samples) by
      using a prescribed procedure. The test materials consisted of duplicate samples
      of acid-hydrolyzed vegetable protein (containing 3-MCPD at 0.029 mg/kg), malt
      extract (0.055 mg/kg), wholemeal bread crumbs (0.030 mg/kg), salami (0.016
      mg/kg), cheese alternative (0.043 mg/kg), and soup powder (split levels at 0.045
      and 0.041 mg/kg). Repeatability ranged from 0.005 to 0.013 mg/kg and
      reproducibility, from 0.010 to 0.027 mg/kg, for the samples tested. Precision
      values were well within statistically predicted levels (HORRAT values of <1 for 5
      of the 6 matrixes tested) and within method criteria prepared by a joint working
      group composed of the United Kingdom Ministry of Agriculture, Fisheries and Food
      and industry representatives. The study demonstrated the satisfactory validation
      of the method for quantifying 3-MCPD at levels of > or = 0.010 mg/kg. The limit
      of detection derived from separate in-house studies was estimated to be 0.005
      mg/kg. The method was adopted First Action by AOAC INTERNATIONAL.

PMID- 11324612
TI  - Determination of crude fat in meat by supercritical fluid extraction: direct
      method: PVM 3:2000.
AB  - Meat samples are prepared by passing meat through a food chopper, bowl cutter, or
      food processor, subsampling the meat, and mixing the meat with granular
      diatomaceous earth. No drying step is necessary. Supercritical CO2 is then used
      to extract crude fat (which is defined as the components of meat that are
      extractable with petroleum ether, without digestion of the sample). Extracted
      material is deposited on glass wool contained in collection vials. After removal
      of any residual moisture from the extracts, percent crude fat is determined by
      weight gain of the collection vial. This method has been peer-verified by 3
      laboratories, for a wide variety of raw and processed meat products containing 6
      28% crude fat. Samples were prepared at the submitting laboratory. Ground samples
      were split into 4 portions, packed in Whirlpack bags, and immediately frozen.
      Frozen samples were sent by overnight room temperature, and percent fat was
      determined (in triplicate), without further processing of the samples. Analysis
      of the samples was completed within 1 week of sample prepara. tion. On the basis
      of this study, it can be estimated that all repeatability and reproducibility
      values are <3.0. Mean accuracy of the direct gravimetric supercritical fluid
      extraction method for meat samples ranged from +0.22 to -1.41 when the method was
      compared with AOAC Method 960.39. Interferences are unlikely but would include
      any nonfat substance that is added to (processed) meat, is soluble in nonpolar
      solvents, and is present in a quantity that would alter results. This method is
      expected to perform equally well for all meats with fat content within the stated
      range of applicability.

PMID- 11324613
TI  - Determination of polydextrose in foods by ion chromatography: collaborative
      study.
AB  - Eight collaborating laboratories assayed 7 blind duplicate pairs of foods for
      polydextrose content. The 7 test sample pairs ranged from low (2%) to high (95%)
      levels. The following foods were prepared with polydextrose mixed into the other
      ingredients and then baked, cooked, or otherwise prepared: milk chocolate candy,
      iced tea, sugar cookie, grape jelly, soft jellied candy, and powdered drink mix.
      Collaborators received a polydextrose standard to develop a calibration curve.
      The method determined polydextrose by ion chromatography, after removal of
      interfering food components (high molecular weight solubles). Repeatability
      standard deviations (RSDr) ranged from 3.93 to 9.04%; reproducibility standard
      deviations (RSDR) ranged from 4.48 to 14.06%. The average recovery was 94%.

PMID- 11324614
TI  - Solid-phase microextraction for the enantiomeric analysis of flavors in
      beverages.
AB  - Solid-phase microextraction combined with gas chromatographic/mass spectrometric
      analysis and separation on a chiral cyclodextrin stationary phase was a rapid,
      reliable technique for profiling chiral aroma compounds in flavored alcoholic
      beverages. Several enantiomeric terpenes, esters, alcohols, norisoprenoids, and
      lactones were identified in berry-, peach-, strawberry-, and citrus-flavored wine
      and malt beverages (wine coolers). Using this technique, we were able to confirm
      the addition of synthetic flavoring to several beverages, consistent with label
      designations.

PMID- 11324615
TI  - Identification of hydrolyzed inulin syrup and high-fructose corn syrup in apple
      juice by capillary gas chromatography: PVM 4:1999.
AB  - A peer-verified, gas chromatographic (GC) method is presented for the
      identification of hydrolyzed inulin syrup (HIS) and high-fructose corn syrup
      (HFCS) in apple juice. The procedure involves determining the Brix value of the
      apple juice or apple juice concentrate and preparing a dilution of the test
      sample to 5.5 degrees Brix. A 100 microL aliquot of the 5.5 degrees Brix test
      solution is then freeze-dried in a GC autosampler vial. The sugars in the freeze
      dried residue are converted to trimethylsilyl derivatives, by the addition of an
      appropriate silylation reagent, and the vial is heated at 75 degrees C for 30
      min. After derivatization, the solution is introduced into a gas chromatograph
      where the analytes are separated on a 30 m, 0.25 mm id DB-5 column. The method
      can use hydrogen, helium, or nitrogen as the carrier gas. The analytes and marker
      compounds are measured by use of a flame ionization detecone of the 2 syrups at 2
      levels. Dilution was ascertained by the presence of retrograde sugar markers
      found in the 2 sugar syrups. All 3 laboratories involved in the study were able
      to identify the correct diluent in the blind, randomly coded, apple juice test
      portions. The levels of dilution in the test portions were 0, 6.9% (HIS), 16.0%
      (HIS), 8.1% (HFCS), and 17.0% (HFCS). No false positive results were reported.
      Quantitative conclusions can be drawn when the same syrup is used for dilution
      and as a reference standard.

PMID- 11324616
TI  - Liquid chromatographic determination of methyl anthranilate in artificially
      flavored nonalcoholic beverages.
AB  - A liquid chromatographic method was developed that provides a simple and rapid
      means of determining methyl anthranilate (MA) in carbonated and noncarbonated,
      artificial grape-flavored, nonalcoholic beverages. The proposed procedure, which
      was applied to 12 different products, uses a Nova-Pak C18 column, a mobile phase
      containing acetonitrile-0.025M KH2PO4 (40 + 60), pH 3.00, and UV detection at 220
      nm. Assay values ranged from 0.35 to 16.6 microg MA/mL. The intralaboratory
      precision (relative standard deviation) for the products ranged from 0.51 to
      2.23% (n = 5), and recoveries via fortification ranged from 83.6 to 102.4%. The
      limits of quantitation and detection were 0.00417 and 0.00125 microg/mL,
      respectively, and the analyte response was linear over a 100-fold concentration
      range (0.0001-0.01 mg/mL).

PMID- 11324617
TI  - Determination of sucrose esters of fatty acids in food additive premixes by gas
      chromatography and confirmation of identity by gas chromatography/mass
      spectrometry.
AB  - A gas chromatographic (GC) method was developed for the determination of sucrose
      monoesters of fatty acids (mono-SuE) and sucrose acetate isobutyrate (SAIB) in
      food additive premixes. Mono-SuE and SAIB fractions were prepared by column
      chromatography with either a C8 or a silica gel solid-phase extraction column.
      The mono-SuE fraction was acetylated and applied to a wide-bore GC column (0.53
      mm x 15 m) by splitless injection for determination. The SAIB fraction was
      applied to the GC column without derivatization. Gas chromatography/mass
      spectrometry was used to confirm the identity of GC peaks. The detection limits
      for mono-SuE and SAIB were 0.005 and 0.01%, respectively. Mono-SuE (C12, C14,
      C16, C18, and C18:1) and SAIB were found in commercial food additive premixes and
      some foods.

PMID- 11324618
TI  - Determination of iodine-131 at low levels in milk: collaborative study.
AB  - The official method for the determination of iodine-131 in milk has a lower limit
      of detection (LLD) of 10 pCi/L (0.37 Bq/L). The Nuclear Regulatory Commission had
      recommended that a method claiming to have an LLD of <0.3 pCi/L (<1.1E-02 Bq/L)
      be used. That method, which is capable of measuring iodine-131 below the level of
      detection of the Official Method, was collaboratively studied. The method uses a
      palladium iodide precipitate to concentrate the iodine-131 and measures (counts)
      its 364 keV gamma energy in coincidence with the beta decay or with a low
      background beta-counting system. The study was performed by using 3
      concentrations of iodine-131 in milk: 2.6, 5.0, and 8.0 pCi/L (9.62E-02, 1.85E
      01, and 2.96E-01 Bq/L, respectively). Eleven laboratories agreed to participate
      in the study. Eight laboratories submitted data for the study. The averages of
      the results were 2.68, 5.30, and 8.12 pCi/L (9.92E-02, 1.96E-01, and 3.00E-01
      Bq/L, respectively), respectively. The intra- and interlaboratory variations were
      acceptable. The method was adopted First Action by AOAC INTERNATIONAL.

PMID- 11324619
TI  - Variables affecting simulated use determination of residual ethylene oxide in
      medical devices.
AB  - In autumn 1993, AAMI/ST/WG 63, Sterilization Residuals Working Group undertook
      the task of studying factors involved in determining the amount of residual
      ethylene oxide in medical devices after sterilization and developing a protocol
      for controlling the relevant variables. The protocol was evaluated by conducting
      a round robin study consisting of 8 participating laboratories from around the
      country. Results of this round robin study demonstrated the range over which
      results may vary despite controls placed on the time and temperature at which
      determinations were conducted. The data from the study suggest that small, random
      variations in technique during short sample extraction times can lead to
      variability in the results. Variables such as initial water temperature, oven
      temperature, weighing of sample, and length of extraction should be carefully
      controlled. Inherent variations in the material composition of similar devices
      are possible contributing factors. The efforts of this working group and the
      subsequent evaluation and discussion of its findings are presented.

PMID- 11324620
TI  - Monitoring of pesticide residues in Egyptian fruits and vegetables during 1996.
AB  - Samples of the most common fruits and vegetables were collected from 8 local
      markets in 6 governorates. These 1,579 samples were analyzed for residues of 53
      pesticides, which included organophosphorus and organonitrogen compounds and some
      synthetic pyrethroids. Samples were also analyzed for residues of organochlorine
      pesticides, although they had been prohibited from use several years ago. Only
      510 of the 1,579 samples were analyzed for dithiocarbamate pesticide residues,
      which were determined as CS2. Overall, 76.1 % of the total analyzed samples had
      no detectable residues, 23.9% contained detectable residues, and 2.59% contained
      residues that exceeded maximum residue limits. For individual crops, contaminated
      samples ranged from 0 to 96% of the number of samples analyzed. However, the
      highest violative percentage for samples of individual crops was 12.5.
      Chlorpyrifos, carbaryl, dimethoate, bromopropylate, and profenofos were the
      violative pesticides determined in fruit and vegetable samples. The results of
      the current study demonstrated that no restricted or banned pesticides such as
      DDT, HCH, and their isomers were found in any of the samples analyzed.
      Dithiocarbamate residues were detected in 9.4% of the 510 samples analyzed, with
      a violative percentage of 0.39, representing one grape sample and one peach
      sample.

PMID- 11324621
TI  - Multiwavelength spectral correction for the simultaneous determination of Cu(II),
      Fe(II), and Zn(II) with 1-(5-bromo-2-pyridylazo)-2-naphthol-6-sulfonic acid.
AB  - A new analytical method is described for the simultaneous determination of
      various components by multiwavelength spectrophotometry. Because of the influence
      of the free ligand and various complexes on spectrophotometric absorption, the
      spectral correction principle was used to establish the calculation matrix
      formula. The 3 sensitive reactions of Cu(II), Fe(II), and Zn(II), with 1-(5-bromo
      2-pyridylazo)-2-naphthol-6-sulfonic acid were studied at pH 10.5. In analyses of
      fortified samples, the recoveries of Fe, Zn, and Cu were between 93.0 and 103%,
      87.0 and 108%, and 92.5 and 108%, respectively; the relative standard deviations
      for 5 determinations of Fe, Zn, and Cu in unfortified ore were 3.6, 5.8, and
      4.5%, respectively.

PMID- 11324623
TI  - Simultaneous determination of imazalil and its major metabolite in citrus fruit
      by solid-phase extraction and capillary gas chromatography with electron capture
      detection.
AB  - A method was developed for the simultaneous determination of imazalil and its
      major metabolite, R 14821, in citrus fruit. This method (designated the SPE
      method) is based on solid-phase extraction (SPE) and capillary gas chromatography
      (GC) with electron-capture detection (ECD). The SPE method is highly sensitive
      for both compounds (limit of detection for each: 0.001 microg/g) and is less time
      consuming than the previously reported method based on repeated liquid-liquid
      partitioning and GC-ECD. Recoveries for 3 levels of fortification (0.02, 0.2, and
      2.5 microg/g) from satsuma mandarins ranged from 94.3 to 96.5% for imazalil and
      from 93.9 to 96.3 % for R 14821, with coefficients of variation (CVs) ranging
      from 3.1 to 6.3% for imazalil and from 4.5 to 5.6% for R 14821. Average residual
      levels found in grapefruit, oranges, and lemons by the SPE method and the
      previously reported method, and the corresponding CVs, were similar.

PMID- 11324622
TI  - Complexation equilibria and spectrophotometric determination of iron(III) with
      resorcylic acid.
AB  - The complexation equilibria of Fe(III) with resorcylic acid (2,4-dihydroxybenzoic
      acid, DHB) were studied spectrophotometrically in ethanol-water (4 + 6, v/v) at
      an ionic strength of 0.1 M NaClO4. The complexation reactions were demonstrated
      and characterized. A simple, rapid, and sensitive method based on the formation
      of the Fe(III)-DHB complex at pH 2.5 (lambdamax = 520 nm, epsilon = 0.8 x 10(4)
      L/mol x cm) was developed for the spectrophotometric determination of Fe(III).
      The effect of diverse ions on the sensitivity of the proposed method was studied.
      The Fe-DHB complex was isolated and characterized by both elemental analysis and
      infrared spectroscopy. The thermal behavior of the complex in dynamic nitrogen
      gas was studied by thermogravimetric and differential thermogravimetric analysis.
      Thermal events encountered throughout the course of decomposition were monitored.
      A computer program was used for regression analysis and for determination of
      kinetic and thermodynamic parameters from experimental nonisothermal
      thermogravimetric data. The proposed method was tested by determinations of iron
      in various synthetic samples and Portland cement materials.

PMID- 11324624
TI  - Determination of arsenic in seafood by focused microwave digestion and hydride
      generation-atomic fluorescence detection.
AB  - A new method was developed for total arsenic determination in seafood products
      such as oysters, mussels, tuna fish, and algae. Matrix decomposition and
      oxidation to arsenate of all the arsenic compounds in the product were completed
      in 25 min by using a 3-step program of focused microwaves (40-120 W) with nitric
      and sulfuric acids. Quantitation was performed by hydride generation-atomic
      fluorescence detection (HG-AFS). Results of method optimization are presented and
      discussed. A detection limit <125 microg/kg arsenic was obtained; the
      quantitation limit was close to 400 microg/kg, with repeatability and
      reproducibility <5% relative standard deviation. Validation was performed by
      analyzing 4Reference Materials (arsenic concentration expressed as mg/kg): The
      National Institute of Standards and Technology SRM 1566a Oyster tissue (14.0 +/-
      1.2); the Bureau Community of Reference (now Standard Measurements & Testing
      Program) CRM 278 Mussel tissue (5.9 +/- 0.2) and CRM 627 Tuna fish (4.8 +/- 0.3);
      and the International Atomic Energy Agency RM 140 Fucus sample (44.3 +/- 2.1).

PMID- 11324625
TI  - Mixed-mode solid-phase extraction and cleanup procedures for the liquid
      chromatographic determination of thiabendazole and carbendazim in fruit juices.
AB  - Solid-phase extraction (SPE) procedures were developed for rapid cleanup and
      determination of thiabendazole and carbendazim in orange, apple, and grape
      juices. Samples were prepared by using an SPE cartridge containing a mixed-mode
      sorbent with both reversed-phase and strong cation-exchange chemistries. Analysis
      was by liquid chromatography with photodiode-array UV detection. Orange juice was
      analyzed by mixed-mode cation-exchange extraction with reversed-phase cleanup;
      the other juices were analyzed by reversed-phase extraction with cation-exchange
      cleanup. Recoveries >80% for carbendazim and >90% for thiabendazole. Quantitation
      limits were 20 microg/L for both analytes.

PMID- 11324626
TI  - Investigation of ketoconazole copper(II) and cobalt(II) complexes and their
      spectrophotometric applications.
AB  - Ketoconazole, as a ligand, reacts quantitatively with copper(II) and cobalt(II)
      to form blue-colored, stable complexes in dichloromethane. These complexes can be
      spectrophotometrically measured at 720 and 612.5 nm in the case of Cu(II) or
      Co(II), respectively. Different factors affecting the reaction such as pH,
      reagent concentration, solvent effect, and time were studied. By using Job's
      method of continuous variation, the stoichiometry of the reaction was found to be
      in the ratio of 1:2, metal:drug, with Cu(II) and Co(II). The stability of the
      complexes formed was also studied. The reaction products were isolated for
      further investigation. The complexes have apparent molar absorptivities of 35.36
      +/- 1.95 and 59.62 +/- 1.87 for Cu(II) and Co(II), respectively. Suggested
      procedures based on the stoichiometric reaction were successfully applied to the
      analysis of the pure drug and its pharmaceutical formulations. The validity of
      the procedures was further ascertained by the method of standard additions. The
      developed method was found to be simple, accurate, and precise when compared with
      the official method of the British Pharmacopoeia.

PMID- 11324627
TI  - Determination of moisture in cheese and cheese products.
AB  - Variables related to oven-drying samples of cheese and cheese products to
      determine moisture content were examined to provide more efficient and
      reproducible methods. Over 6500 samples of cheese were analyzed in an effort to
      modify the current AOAC procedure. The gravity atmospheric oven was unsuitable
      for use in accurate moisture analysis because of wide temperature differentials
      within the oven cavity. Use of this for oven moisture determination resulted in
      higher variance, which corresponded to the high temperature variation within the
      oven. Cheese sample preparation using an Oster blender yielded consistently lower
      variance in final moisture content than did preparation of cheese samples with a
      hand grater, rotary grater, and plug and plunger. Sample size of 3 +/- 0.25 g
      maximized surface area-to-volume ratios and yielded a lower error in final
      moisture content because of better control of ambient weight loss rates. Use of
      combination of disposable 5.5 cm diameter aluminum sample pans with 5.5 cm
      diameter glass fiber filter pads for covers produced a smaller standard deviation
      for moisture analysis than did the AOAC pan and insert cover and filter paper
      covers. All pans must be pre-dried for at least 3 h at 100 degrees C, and the
      glass fiber covers should be pre-dried for 1 h under the same conditions. All
      dried pans and covers must be stored in a desiccator with active desiccant.
      Equipment upgrades from the existing AOAC standard methods provide safer more
      efficient methods of analysis.

PMID- 11324629
TI  - Moisture variations in brine-salted pasta filata cheese.
AB  - A study was made of the moisture distribution in brine-salted pasta filata
      cheese. Brine-salted cheeses usually develop reasonably smooth and predictable
      gradients of decreasing moisture from center to surface, resulting from outward
      diffusion of moisture in response to inward diffusion of salt. However, patterns
      of moisture variation within brine-salted pasta filata cheeses, notably pizza
      cheese, are more variable and less predictable because of the peculiar conditions
      that occur when warm cheese is immersed in cold brine. In this study, cold
      brining resulted in less moisture loss from the cheese surface to the brine. Also
      it created substantial temperature gradients within the cheese, which persisted
      after brining and influenced the movement of moisture within the cheese
      independently of that caused by the inward diffusion of salt. Depending on
      brining conditions and age, pizza cheese may contain decreasing, increasing, or
      irregular gradients of moisture from center to surface, which may vary
      considerably at different locations within a single block. This complicates
      efforts to obtain representative samples for moisture and composition testing.
      Dicing the entire block into small (e.g., 1.5 cm) cubes and collecting a
      composite sample after thorough mixing may serve as a practical sampling approach
      for manufacturers and users of pizza cheese that have ready access to dicing
      equipment.

PMID- 11324628
TI  - Variations of moisture measurements in cheese.
AB  - Data were accumulated during interlaboratory trials for cheese moisture
      determination from laboratories using officially recognized methods: AOAC;
      International Dairy Federation, and Standard Methods for the Examination of Dairy
      Products (SM). In one trial, ranges of means of 5 cheeses were 0.67, 0.56, and
      0.19% for 5, 9, and 8 laboratories, respectively. The lower ranges for the SM
      method were typical of 3 other interlaboratory trials, with ranges of 0.27, 0.34,
      and 0.34% for 6, 7, and 5 laboratories, respectively. Within one laboratory,
      there were no significant differences among the 3 methods, but they all gave
      about 0.2% lower results than 2 other methods, one using freeze-drying, followed
      by drying in a vacuum, the other using cheese that was spread on sand and dried
      in a vacuum oven for 24 h. This finding indicated that none of the officially
      recognized methods removed all the moisture. Data showed that many laboratories
      tended to give either higher or lower results than the mean of all of them in a
      series of 7 interlaboratory trials. Constant results, free of biases or
      systematic errors, are important in application of formulas for prediction of
      yield of cheese for purposes of yield control, but are difficult to obtain. It is
      proposed that results by a laboratory in interlaboratory trials be compared with
      those obtained by one or more reference laboratories using a method that removes
      all the moisture from cheese. The difference would be applied as a constant in
      the predictive yield formula. That difference would likely be best as a running
      mean of differences in an ongoing series of trials. The reference laboratories
      would use frozen samples for quality control to ensure uniformity of results
      among trials. Mean moistures of 36.10 and 36.11% were obtained on subsamples
      before and after freezing for 7 months.

PMID- 11324630
TI  - Moisture nonuniformity and sampling errors in large cheddar cheese blocks.
AB  - A study was made of the impact of nonuniform moisture distribution in 290 kg
      blocks of cheese on the accuracy of sampling the cheese for moisture content. The
      range of moisture from center to outside surfaces of the blocks was about 5%. The
      temperature gradient, developed in the first 24-48 h after cheese making, drove
      the moisture migration from warm to cold areas in the cheese blocks during
      initial cooling. The moisture gradient from center to outside of each block, the
      non-symmetrical nature of the gradient, and the actual length of the core sample
      all contributed to random and systemic error in sampling within a single cheese
      plant. It was concluded that average moisture differences from vat to vat in a
      factory were small, and large variations in moisture tests were due to sampling
      errors.

PMID- 11324631
TI  - Movement of moisture in refrigerated cheese samples transferred to room
      temperature.
AB  - When cheese samples refrigerated at 4 degrees C in 120 mL plastic tubs were
      transferred to room temperature at 23 degrees C, moisture began to move from the
      warmer surface to the cooler interior; the difference after 1 h was 0.2-0.4%.
      Others had observed that moisture moved from the interior of warmer blocks of
      cheese to the cooler surface during cooling at the end of cheese manufacture. In
      loosely packed cheese prepared for analysis, part of the moisture movement may
      have been due to evaporation from the warmer surface and condensation on the
      cooler cheese. It is recommended that cheese be prepared for analysis immediately
      before weighing. Cheese samples that have been refrigerated, as in
      interlaboratory trials, should also be remixed or prepared again.

PMID- 11324632
TI  - Measuring moisture in cheese by near infrared absorption spectroscopy.
AB  - Data in the literature indicate that the measurement of moisture in cheese by
      near infrared transmittance (NIT) is more accurate than by reflectance (NIR). The
      accuracy of the NIT measurement (SEP) was calculated for Edam, Gouda, Brie,
      Colby, and Cheddar. A range of SEP values (0.12-0.35) was obtained using
      different methods of calibration for different types of samples. There was close
      agreement between these results, as they related to the precision of the
      reference method. The calibration validation technique described as Standard
      Error of Cross Validation (SECV) generated results that compared very closely to
      the equivalent SEP values for independent sample sets.

PMID- 11324633
TI  - Summaries for patients. Trial of a drug to decrease the risk for heart disease in
      patients with mild kidney failure.

PMID- 11324634
TI  - Summaries for patients. The effect of age on the risk for complications and death
      after noncardiac surgery.

PMID- 11324635
TI  - Summaries for patients. Treatment and outcomes of heart attacks in people with
      pacemakers.

PMID- 11324636
TI  - Another cinder in the eye of the Marlboro man.

PMID- 11324637
TI  - Pure red cell aplasia in patients with chronic lymphocytic leukaemia treated with
      cladribine.

PMID- 11324638
TI  - Rituximab: a very efficient therapy in cold agglutinins and refractory autoimmune
      haemolytic anaemia associated with CD20-positive, low-grade non-Hodgkin's
      lymphoma.

PMID- 11324639
TI  - Partial tetrasomy of 9P: a rare chromosomal abnormality in polycythaemia vera.

PMID- 11324640
TI  - Low activity of von Willebrand factor-cleaving protease is not restricted to
      patients suffering from thrombotic thrombocytopenic purpura.

PMID- 11324641
TI  - Heterozygosity for the thiopurine methyltransferase *3A allele in an acute non
      lymphoblastic leukaemia patient with delayed marrow regeneration following H-DAT
      chemotherapy.

PMID- 11324642
TI  - Successful recovery from human immunodeficiency virus (HIV)-associated
      haemophagocytic syndrome treated with highly active anti-retroviral therapy in a
      patient with HIV infection.

PMID- 11324643
TI  - From the Centers for Disease Control and Prevention. Influenza activity--United
      States, 2000-01 season.

PMID- 11324644
TI  - From the Centers for Disease Control and Prevention. Influenza B virus outbreak
      in a cruise ship--Northern Europe, 2000.

PMID- 11324645
TI  - From the Centers for Disease Control and Prevention. Physical activity trends-
      United States, 1990-1998.

PMID- 11324646
TI  - From the Centers for Disease Control and Prevention. Sudden death in a traveler
      following halofantrine administration--Togo, 2000.

PMID- 11324647
TI  - JAMA patient page. Lymphoma.

PMID- 11324648
TI  - A 73-year-old man with chronic lymphocytic leukaemia and a haemorrhagic pleural
      effusion.
AB  - A 73-year-old man presented with haemorrhagic pleural effusion, having been
      diagnosed with chronic lymphocytic leukaemia (CLL). The differential diagnosis of
      haemorrhagic pleural effusion is considered. Tuberculosis and pleural
      infiltration of CLL are considered most likely. Pleural biopsy confirms the
      diagnosis of pleural involvement of CLL in this case. Although pleural
      involvement of CLL has been reported several times the presentation of pleural
      effusion as the first symptom of CLL has not previously been described.

PMID- 11324649
TI  - Effects of aging and gender on interhemispheric function.
AB  - The ability of the two hemispheres of the brain to communicate with one another
      via the corpus callosum is important for a wide variety of sensory, motor, and
      cognitive functions, many of them communication related. Anatomical evidence
      suggests that aging results in structural changes in the corpus callosum and that
      the course over time of age-related changes in corpus callosum structure may
      depend on the gender of the individual. Further, it has been hypothesized that
      age- and gender-related changes in corpus callosum structure may result in
      concomitant decreased performance on tasks that are reliant on interhemispheric
      integrity. The purpose of this study was to investigate the effects of age and
      gender on auditory behavioral and visuomotor temporal indices of interhemispheric
      function across the life span of the normal adult. Results from 120 consistently
      right-handed adults from age 20 to 75 years revealed that interhemispheric
      integrity, as measured by dichotic listening, auditory temporal patterning, and
      visuomotor interhemispheric transfer time tasks, decreases relatively early in
      the adult life span (i.e., between the ages of 40 and 55 years) and shows no
      further decrease thereafter. In addition, the course over time of
      interhemispheric decline is different for men compared to women for some tasks.
      These findings suggest that decreased interhemispheric function may be a possible
      factor contributing to auditory and communication difficulties experienced by
      aging adults. In addition, results of this study hold implications for the
      clinical assessment of interhemispheric function in aging adults and for future
      research into the functional ramifications of decreased multimodality
      interhemispheric transfer.

PMID- 11324650
TI  - Relationships among speech perception, production, language, hearing loss, and
      age in children with impaired hearing.
AB  - Eighty-seven primary-school children with impaired hearing were evaluated using
      speech perception, production, and language measures over a 3-year period. Forty
      seven children with a mean unaided pure-tone-average hearing loss of 106 dB HL
      used a 22-electrode cochlear implant, and 40 with a mean unaided pure-tone
      average hearing loss of 78 dB HL were fitted with hearing aids. All children were
      enrolled in oral/aural habilitation programs, and most attended integrated
      classes with normally hearing children for part of the time at school. Multiple
      linear regression was used to describe the relationships among the speech
      perception, production, and language measures, and the trends over time. Little
      difference in the level of performance and trends was found for the two groups of
      children, so the perceptual effect of the implant is equivalent, on average, to
      an improvement of about 28 dB in hearing thresholds. Scores on the Peabody
      Picture Vocabulary Test (PPVT) and the Clinical Evaluation of Language
      Fundamentals showed an upward trend at about 60% of the rate for normally hearing
      children. Rates of improvement for individual children were not correlated
      significantly with degree of hearing loss. The children showed a wide scatter
      about the average speech production score of 40% of words correctly produced in
      spontaneous conversations, with no significant upward trend with age. Scores on
      the open-set Consonant-Nucleus-Consonant (CNC) monosyllabic word test and the
      Bench-Kowal-Bamford (BKB) sentence test were strongly related to language level
      (as measured by an equivalent age on the PPVT) and speech production scores for
      both auditory-visual and auditory test conditions. After allowing for differences
      in language, speech perception scores in the auditory test condition showed a
      slight downward trend over time, which is consistent with the known biological
      effects of hearing loss on the auditory periphery and brainstem. Speech
      perception scores in the auditory condition also decreased significantly by about
      5% for every 10 dB of hearing loss in the hearing aid group. The regression
      analysis model allows separation of the effects of language, speech production,
      and hearing levels on speech perception scores so that the effects of
      habilitation and training in these areas can be observed and/or predicted. The
      model suggests that most of the children in the study will reach a level of over
      90% sentence recognition in the auditory-visual condition when their language
      becomes equivalent to that of a normally hearing 7-year-old, but they will enter
      secondary school at age 12 with an average language delay of about 4 or 5 years
      unless they receive concentrated and effective language training.

PMID- 11324651
TI  - An evaluation of the effects of two treatment approaches for teachers with voice
      disorders: a prospective randomized clinical trial.
AB  - Teachers commonly report voice problems and often seek medical assistance for
      voice-related complaints. Despite the prevalence of voice disorders within this
      occupation, there are no studies evaluating the effectiveness of treatment
      programs designed to remedy the voice problems of teachers. To assess the
      functional effects of two voice therapy approaches, 58 voice-disordered teachers
      were randomly assigned to 1 of 3 groups: vocal hygiene (VH, n = 20), vocal
      function exercises (VFE, n = 19), and a nontreatment control group (CON, n = 19).
      Subjects completed the Voice Handicap Index (VHI)-an instrument designed to
      appraise the self-perceived psychosocial consequences of voice disorders-before
      and following a 6-week treatment phase. The VFE and VH subjects also completed a
      posttreatment questionnaire regarding the perceived benefits of treatment. Only
      the group who adhered to the VFE regimen reported a significant reduction in mean
      VHI scores (p <.0002). Furthermore, when compared to the VH group, the exercise
      group reported more overall voice improvement (p < .05) and greater ease (p <
      .02) and clarity (p < .01) in their speaking and singing voice after treatment.
      These findings suggest that the VFE should be considered as a useful alternative
      or adjunct to vocal hygiene programs in the treatment of voice problems in
      teachers.

PMID- 11324652
TI  - Control of vocal loudness in young and old adults.
AB  - This study examined the effect of aging on respiratory and laryngeal mechanisms
      involved in vocal loudness control. Simultaneous measures of subglottal pressure
      and electromyographic (EMG) activity from the thyroarytenoid (TA), lateral
      cricoarytenoid (LCA), and cricothyroid (CT) muscles were investigated in young
      and old individuals while they attempted to phonate at three loudness levels,
      "soft," "comfortable," and "loud." Voice sound pressure level (SPL) and
      fundamental frequency (F ) measures were also obtained. Across loudness
      conditions, subglottal pressure levels were similar for both age groups.
      Laryngeal EMG measures tended to be lower and more variable for old compared with
      young individuals. These differences were most apparent for the TA muscle.
      Finally, across the three loudness conditions, the old individuals generated SPLs
      that were lower overall than those produced by the young individuals but
      modulated loudness levels in a manner similar to that of the young subjects.
      These findings suggest that the laryngeal mechanism may be more affected than the
      respiratory system in these old individuals and that these changes may affect
      vocal loudness levels.

PMID- 11324653
TI  - The effects of masseter tendon vibration on nonspeech oral movements and vowel
      gestures.
AB  - The role of proprioception in speech and oral motor control was investigated by
      applying tendon vibration to the masseter during vowel production and nonspeech
      oral movements. Measures were made of peak jaw-opening amplitude, jaw-opening
      velocity, and movement time in both vibration and nonvibration conditions.
      Generally, the tendon vibration caused a consistent and marked reduction in the
      amplitude and velocity of jaw-opening movements for each subject in both tasks.
      Movement time remained consistent across the vibration conditions for both tasks.
      These results indicate that masseter tendon vibration causes significant changes
      in jaw kinematics during simple speech gestures and nonspeech movements. These
      findings are consistent with the documented effects of tendon vibration on limb
      movements. The study demonstrates that tendon vibration is a potent tool for
      investigating proprioception in speech and oral motor control.

PMID- 11324654
TI  - Senescent expression of genes coding tropoelastin, elastase, lysyl oxidase, and
      tissue inhibitors of metalloproteinases in rat vocal folds: comparison with skin
      and lungs.
AB  - Histology studies indicate that vocal elastin content accumulates with age,
      suggesting possible contribution of elastin to age-associated voice changes.
      However, the underlying mechanism remains unclear. Using a reverse-transcriptase
      polymerase chain reaction (RT-PCR), mRNA levels of tropoelastin, elastase, lysyl
      oxidase, and tissue inhibitors of metalloproteinases (TIMP-1 to TIMP-4) were
      measured in vocal folds, tail skin, and lungs of rats at ages 1.5 +/- 0.5 weeks
      (neonatal), 6.0 +/- 0.5 months (adult), and 24 +/- 0.5 months (elderly). Vocal
      expression of both tropoelastin and lysyl oxidase peaks during the neonatal
      stage, followed by a significant decrease. Gene expression for elastase in the
      vocal folds of adult rats is not dissimilar to the neonatal levels. The levels in
      the elderly rots, however, show marked increase, to as much as 201% of the
      neonatal levels (p < .05). On the other hand, there is no conspicuous age
      dependent variation in vocal expression of TIMPs. Gene expression of tropoelastin
      was similar in rat skin, lung, and vocal folds. In summary, compared to what is
      found in adult rats, there is a significant up-regulation in the expression of
      vocal elastase in the elderly animals in the presence of unchanged vocal
      expression of tropoelastin, lysyl oxidase, and TIMPs. As senescence occurs in
      both adult and elderly rats, tropoelastin and elastase expression are most
      affected. Gene expression for proteins affecting the amount of elastin in the
      vocal fold extracellular matrix does vary with age. These results may not be
      directly applicable to humans, because biomechanical forces experienced by human
      folds are likely different than those experienced by rats. However, in the
      absence of biomechanical forces experienced by humans, rat lungs, skin, and vocal
      folds display similar profiles of expression of genes coding the above-mentioned
      molecules. Similar profiles of expression for elastin genes across different
      tissue types not sharing similar environments suggests a common mechanism
      influencing senescence of these tissues. Human folds likely share a common
      similar mechanism of senescence with other organ systems, although organ-specific
      factors (oscillation, mechanical forces) are also likely operating.

PMID- 11324655
TI  - Acoustic discrimination of pathological voice: sustained vowels versus continuous
      speech.
AB  - We investigated the ability of acoustic measures to discriminate between normal
      and pathological talkers. Two groups of measures were compared: (a) those
      extracted from sustained vowels and (b) those based on continuous speech samples.
      Nine acoustic measures, which include fundamental frequency and amplitude
      perturbation measures, long term average spectral measures, and glottal noise
      measures were extracted from both sustained vowel and continuous speech samples.
      Our experiments were performed on a published database of 53 normal talkers and
      175 talkers with a pathological voice. The classification performance of the nine
      acoustic measures was quantified using linear discriminant analysis and receiver
      operating characteristic (ROC) curve analysis. When individual measures were
      considered in isolation, classification was more accurate for measures extracted
      from sustained vowels than for those based on continuous speech samples.
      Classification accuracy improved when combinations of acoustic parameters were
      considered. For such combinations of measures, classification results were
      comparable for measures extracted from continuous speech samples and for those
      based on sustained vowels.

PMID- 11324656
TI  - Variation in anticipatory coarticulation with changes in clarity and rate.
AB  - This study tests the hypothesis that the relative timing, or coarticulation, of
      articulatory movements at VC and CV boundaries is influenced by both the
      listener's requirement for clarity and the speaker's strategy to economize
      effort. Movement and acoustic data were collected from 7 subjects who spoke in
      three conditions: normal, clear, and fast. It was predicted that fast speech
      would show more coarticulation and clear speech would show less coarticulation
      than normal speech. The speech materials were designed to investigate
      coarticulation in the movements of the upper lip and tongue. They consisted of
      repetitions of [iC(n)u] utterances embedded in carrier phrases, where the number
      of consonants, n, ranged from 1 to 3. Analyses focused on kinematic measures and
      the amount of coarticulation (overlap) of the /i-u/ transition movement with the
      acoustic interval of the /i/. The consonant-string duration was longest in the
      clear speaking condition and shortest in the fast condition. Compared to the
      normal condition, peak velocities were higher in the fast and clear speaking
      conditions, indicating increased effort. The influences of speaking condition on
      coarticulation and on the formants of the /i/ were small. Thus, even though there
      was evidence of increased effort in the clear and fast conditions, the
      hypothesized effects of a trade-off between clarity and economy of effort were
      minimally evident in formant values for /i/ and measures of coarticulation.

PMID- 11324657
TI  - Phonatory effects of body fluid removal.
AB  - Adequate body and vocal fold hydration are believed to be critical to phonation.
      We hypothesized that body fluid reduction, without dehydration, would increase
      phonation threshold pressure (P(th)) and be associated with patient-perceived
      increases in phonatory effort and worsening voice quality. Using a single
      subject, full-reversal design, a controlled volume of body fluid was repeatedly
      removed via ultrafiltration from adults with end stage renal disease (2 women, 4
      men, ages 40-85 yrs). Two additional men (ages 81 and 68 yrs) served as placebo
      and healthy true controls, respectively. P(th), vocal effort and quality, blood
      pressure, and heart rate were assessed longitudinally. P(th) increased
      significantly with fluid volume reduction (3-4% of body weight from a
      hypervolemic to a grossly normovolemic body state) and reversed to baseline with
      fluid replacement in 4 of 6 treated subjects. Effects were observed with net
      ultrafiltration rates greater than or equal to 1.0 L/h; these effects were not
      observed in control subjects. Fluid loss accounted for 31.6% of variance in P(th)
      and 40.0% of variance in perceived vocal effort. Heart rate, systolic blood
      pressure, and/or diastolic blood pressure were significantly correlated with
      P(th) or fluid volume reduction in 6 subjects, including the placebo control (
      .70 < or = r < or = -.44). Results indicate that substantial extracellular volume
      depletion without body dehydration causes voice symptoms, an effect possibly
      mediated by autonomic nervous control. We propose that mechanisms intrinsic to
      the vocal fold regulate its water flux and respond to hydration challenges.

PMID- 11324658
TI  - The young child's awareness of stuttering-like disfluency.
AB  - The emergence of awareness of stuttering has been an important factor in
      theoretical and clinical considerations for early childhood stuttering. The
      present research program is aimed at studying the development of awareness of
      stuttering-like disfluency in normally fluent preschool and first-grade children
      using responses to video speech samples. A total of 79 children in five different
      age groups were asked to discriminate between the speech (fluent and disfluent)
      of two puppets, identify with the one who speaks like them, and evaluate the
      disfluent and fluent speech of the puppets. It was found that from age 3,
      children show evidence of awareness of the disfluency used in the study, but most
      children reached full awareness at age 5. Also, negative evaluation of disfluent
      speech is observed from age 4. Theoretical and clinical implications are
      discussed.

PMID- 11324659
TI  - SLD is not stuttering.

PMID- 11324660
TI  - Perceptual discrimination of speech sounds in developmental dyslexia.
AB  - Experiments previously reported in the literature suggest that people with
      dyslexia have a deficit in categorical perception. However, it is still unclear
      whether the deficit is specific to the perception of speech sounds or whether it
      more generally affects auditory function. In order to investigate the
      relationship between categorical perception and dyslexia, as well as the nature
      of this categorization deficit, speech specific or not, the discrimination
      responses of children who have dyslexia and those of average readers to sinewave
      analogues of speech sounds were compared. These analogues were presented in two
      different conditions, either as nonspeech whistles or as speech sounds. Results
      showed that children with dyslexia are less categorical than average readers in
      the speech condition, mainly because they are better at discriminating acoustic
      differences between stimuli belonging to the same category. In the nonspeech
      condition, discrimination was also better for children with dyslexia, but
      differences in categorical perception were less clear-cut. Further, the location
      of the categorical boundary on the stimulus continuum differed between speech and
      nonspeech conditions. As a whole, this study shows that categorical deficit in
      children with dyslexia results primarily from an increased perceptibility of
      within-category differences and that it has a speech-specific component. These
      findings may have profound implications for learning and re-education.

PMID- 11324661
TI  - Mechanisms of discourse comprehension impairment after right hemisphere brain
      damage: suppression in inferential ambiguity resolution.
AB  - This study examined the generality of a previous finding indicating that
      difficulty suppressing or inhibiting context-inappropriate interpretations is an
      important predictor of narrative discourse comprehension for adults with right
      brain damage (RBD) (C. A. Tompkins, A. Baumgaertner, M. T. Lehman, & W.
      Fassbinder, 2000). Forty adults with RBD and 39 without brain damage listened to
      two-sentence stimuli and judged whether a probe word fit with the overall
      stimulus meaning. An ambiguous initial sentence elicited both dominant and less
      preferred inferences, and the second sentence resolved the ambiguity toward the
      initially less-likely interpretation. Probes represented the dominant inference
      for the first sentence and were presented at two poststimulus intervals. Probe
      judgment response times indicated that neither group suppressed the eventually
      inappropriate inferences in the time intervals studied. However, multiple
      regression analysis demonstrated that for individual participants with RBD, the
      extent of suppression from one interval to the next was a significant predictor
      of performance on a specialized measure of inference comprehension. The
      discussion evaluates these findings and identifies directions for future
      research.

PMID- 11324662
TI  - Speed of processing in children with specific language impairment.
AB  - The aim of the present study was to investigate the speed with which children
      with specific language impairment (SLI) respond on a range of tasks. Seventy
      seven third-grade children participated in 10 different tasks (involving a total
      of 41 conditions), including nonlinguistic and linguistic activities. Mean
      response times (RTs) of children with SLI (n = 29) increased as a function of
      mean RTs of children with normal language (NLD, n = 29) under each of three
      different regression models; children with SLI responded more slowly across all
      task conditions, and also when linguistic and nonlinguistic tasks were analyzed
      separately. Children with nonspecific language impairment (NLI) were also
      included (n = 19). The results were similar to those for children with SLI, but
      the degree of slowing was greater. The results of the group analyses support the
      hypothesis that speed of processing in children with SLI is generally slower than
      that of children with normal language. However, some children with SLI do not
      appear to show deficits of this type.

PMID- 11324663
TI  - Validation of the language development survey (LDS): a parent report tool for
      identifying language delay in toddlers.
AB  - Two studies are reported demonstrating the reliability, validity, and clinical
      utility of the Language Development Survey (LDS; L. Rescorla, 1989) as a
      screening tool for the identification of expressive language delay in toddlers.
      In Study 1, 422 children (ages 24-26 months) were screened with the LDS in an
      epidemiological survey. The LDS manifested excellent concurrent validity with a
      brief direct screening measure of expressive vocabulary. Using the Rescorla
      (1989) Delay 3 cutoff of fewer than 50 words or no word combinations, 9.7% of the
      sample were language delayed (32 boys, 9 girls). In Study 2, 33 children
      identified as "at-risk" by the LDS Delay 3 cutoff and 33 typically developing
      children, matched on age, socioeconomic status, and gender, were seen for in
      depth follow-up assessment approximately 3 weeks later. The LDS test-retest
      reliability was .97. The LDS correlated highly with Reynell Receptive and
      Expressive Language Scale scores, Bayley Mental Development Index, and Vineland
      Adaptive Behavior Composite. Sensitivity, specificity, positive predictive value,
      and negative predictive value between the screening LDS and the follow-up Reynell
      Expressive Language Scale were generally impressive. Finally, the at-risk group
      scored significantly lower than the LDS-identified typically developing group on
      all follow-up measures except the Child Behavior Checklist/2-3.

PMID- 11324664
TI  - General slowing in language impairment: methodological considerations in testing
      the hypothesis.
AB  - Although the general slowing hypothesis of language impairment (LI) is well
      established, the conventional method to test the hypothesis is controversial.
      This paper compares the usual method, ordinary least squares regression (OLS),
      with another method, hierarchical linear modeling with random coefficients (HLM).
      The analyses used available response time (RT) data from studies of perceptual
      motor, cognitive, and language skills of LI and chronological-age-matched (CA)
      groups. The data set included RT measures from 25 studies investigating 20
      different tasks (e.g., auditory detection, mental rotation, and word recognition
      tasks). OLS and HLM analyses of the RT data yielded very different results. OLS
      supported general slowing for the LI groups, and indicated that they were
      significantly slower than CA groups across studies by an overall estimate of 10%.
      HLM indicated a larger average extent of LI slowing (18%). However, the
      variability around this average was much greater than that yielded by OLS, and
      the extent of slowing was not statistically significant. Importantly, HLM showed
      a significant difference in the RT relation between LI and CA groups across
      studies, indicating that study-specific slowing, rather than general slowing
      across studies, was present. A separate HLM analysis of two types of language
      tasks, picture naming and word recognition, was performed. Although the extent of
      slowing was equivalent across these tasks, the slowing was minimal (2%) and not
      significant. Methodological limitations of each analysis to assess general
      slowing are highlighted.

PMID- 11324665
TI  - Hypophosphatemic rickets presenting as recurring pedal stress fractures in a
      middle-aged woman.
AB  - Stress fractures frequently occur from overtraining. When stress fractures recur,
      underlying metabolic abnormalities should be ruled out. We report a middle-aged
      woman in whom such an evaluation demonstrated previously undiagnosed
      hypophosphatemic rickets after she presented with recurring stress fractures in
      her feet. Treatment with phosphate and calcitriol was associated with clinical
      improvement that would likely not have occurred without this intervention. Any
      patient with recurring stress fractures should be evaluated with several
      screening laboratory tests, metabolic bone x-rays, and a measurement of bone
      mineral density.

PMID- 11324666
TI  - Neurilemoma of the medial plantar nerve: a case report and literature review.
AB  - A neurilemoma is an uncommon, benign, encapsulated neoplasm whose origin is
      derived from the Schwann cells. Its incidence in the foot is uncommon. A review
      of the literature, etiology, incidence, clinical presentation, histology,
      differential diagnosis, and treatment are discussed. The authors present a case
      of a neurilemoma of the medial plantar nerve of the foot.

PMID- 11324667
TI  - Hypertrophic sustentaculum tali causing a tarsal tunnel syndrome: a case report.
AB  - A case report of tarsal tunnel syndrome caused by a hypertrophic sustentaculum
      tali is presented. This is the first reported case secondary to this etiology.
      Complete resolution of the patient's symptoms has been obtained through resection
      of the hypertrophic anatomy. The authors also discuss possible etiologies of
      tarsal tunnel syndrome.

PMID- 11324668
TI  - "Floating tibia-talus complex"--an ipsilateral dislocation of the knee and the
      subtalar joint in an elderly patient: a case report and review of the literature.
AB  - Knee dislocation is defined as a radiographically confirmed total loss of the
      tibiofemoral articulation. This rare injury is believed to be the result of a
      high-impact trauma. Knee dislocations are classified according the direction of
      tibial displacement with respect to the femur. Subtalar dislocation is the
      simultaneous dislocation of the distal articulations of the talus at both the
      talocalcaneal and talonavicular joints. These injuries are also quite rare and
      are mostly (80%-85%) classified as medial subtalar dislocations with the
      calcaneus lying medially, the head of the talus being prominent dorsolaterally
      and the navicular located medial and dorsal to the talar head. The authors report
      the case of an elderly patient who suffered ipsilateral anterior dislocation of
      his left knee and medial subtalar dislocation of his left foot. The authors
      believe this to be the first presentation in the English literature of an
      ipsilateral combination of these two injuries on the same limb.

PMID- 11324669
TI  - Unassisted locking-suture technique for bunionectomy capsular closure.

PMID- 11324670
TI  - Metastatic malignant melanoma to the foot and ankle.

PMID- 11324671
TI  - The incidence of lateral talar dome lesions in SER IV ankle fractures.

PMID- 11324672
TI  - Minimal invasive surgery of the foot and ankle.

PMID- 11324673
TI  - Computer-assisted assessment of lateral column movement following plantar fascial
      release: a cadaveric study.
AB  - In patients who fail conservative treatment, releasing the plantar fascia
      relieves heel pain but destabilizes the lateral column of the foot. After
      surgery, pain can present in the area of the sinus tarsi, extensor digitorum
      brevis muscle, between the fourth and fifth metatarsals, and at the
      calcaneocuboid joint. The precise mechanism and involved structures for this
      painful compensation remains unclear. The authors hypothesized that the lateral
      plantar fascial band, bifurcate and cervical ligaments, lateral talocalcaneal
      ligament, and interosseous talocalcaneal ligament become excessively strained
      after this surgery. Using eight cadaver lower extremity limbs amputated 7 cm
      above the ankle joint, structural changes in the foot in response to staged
      release of the plantar fascia were measured. All ligament, tendon, and osseous
      structures were exposed along the plantar, medial, and lateral aspects of the
      foot and ankle. Using a servohydraulic system, compressive loads in increasing
      increments (50 lbs) were applied along the tibial axis. Tissue and bony structure
      displacement in the foot was measured using images electronically captured from
      two fixed cameras and a digital camera following each load change. All
      measurements were made in pixels and converted to millimeters in a spreadsheet
      program. Except for plantar fascial measurements, data were expressed as
      percentage of initial baseline. As expected, increasing compressive loads changed
      all measurements [repeated measures ANOVA, p<.04]. When releasing the plantar
      fascia, the inferior sinus tarsi space widened (intact, 85.4+/-10.8%; 1/4
      release, 87.7+/-13.0; 1/2 release, 88.3+/-9.2; 3/4 release, 91.2+/-8.8; p<.04).
      Lateral length increased and medial height decreased, while medial length and
      lateral height were unchanged as the fascia was sequentially released.
      Significant movement of the inferior sinus tarsi strained the bifurcate and
      cervical ligaments, the lateral talocalcaneal ligament, and interosseous
      talocaneal ligament, which may account for pain following surgery. The initial
      1/4 cut of the plantar fascia exerted the greatest mechanical alteration of the
      foot, suggesting that a partial release may relieve heel pain while optimizing
      the patient's chances of maintaining structural integrity with 75% of the plantar
      fascia intact.

PMID- 11324674
TI  - Critical evaluation of the modified Lapidus procedure.
AB  - The modified Lapidus procedure has been used for treatment of hallux abducto
      valgus for many years, yet only a handful of reports evaluate procedure outcome.
      The purpose of this investigation was twofold: 1) to provide a retrospective
      outcome analysis of the modified Lapidus procedure using subjective and objective
      criteria, and 2) to evaluate procedure outcome in patient populations with
      differing functional demands: athletes, active patients, and sedentary patients.
      Thirty-four patients (42 feet) had the modified Lapidus procedure performed by
      the senior author (R.T.B.) over a 7-year period. Nine patients were lost to
      follow-up leaving 25 patients (32 feet) for study inclusion. Twenty-three females
      and two males with average age 44.4 years (range 15-71 years) were evaluated at
      an average follow-up time of 39 months (range 13-91 months). Evaluation consisted
      of subjective questionnaire, physical examination, and radiographic assessment.
      Subjective evaluation revealed that 78% of patients rated surgery "completely" or
      "very" effective. Athletes demonstrated lower return to preoperative activity
      levels (30%) than did active patients (86%) and sedentary patients (75%), but
      this was not statistically significant. Seventy-seven percent of athletes rated
      surgery "completely" or "very" effective. Postoperative intermetatarsal angle
      averaged 8.2 degrees (range -2 to 15) and first metatarsophalangeal joint
      dorsiflexion averaged 62.6 degrees (range 20- 90 degrees). Intermetatarsal angle
      correction to 10 degrees or less and postoperative first metatarso-phalangeal
      joint dorsiflexion 45 degrees or greater correlated with improved subjective
      results. The modified Lapidus procedure is an effective procedure in patients
      with hypermobility of the first metatarsocuneiform joint. Success is dependent on
      patient selection, meticulous surgical technique and comprehensive postoperative
      management.

PMID- 11324675
TI  - Posterolateral release for idiopathic clubfoot: review of 18 patients.
AB  - The authors treated and reviewed 18 patients with 26 idiopathic clubfeet by
      posterolateral release and elongation of the tendo Achillis at a mean age of 14.6
      months (range 7-32 months). The mean follow-up of these patients was 43 months
      (range 6- 100 months). Function, appearance, and pain were studied. The mean
      ankle dorsiflexion was 20 degrees at the time of review. In all but one case, the
      hindfoot equinus had been well corrected. Subtalar movement was 75% of normal in
      six feet, and 50% of normal in 16 feet. Revision of the posterolateral release
      combined with anteromedial release was carried out for six patients with residual
      hindfoot varus and forefoot adduction at an average of 13.5 months following the
      initial procedure. In one patient, the deformity was overcorrected, but the
      results of the rest of the revision operations were otherwise good. No skin or
      wound problems were observed in this series. In conclusion, of 26 feet undergoing
      posterolateral release for severe clubfoot, 70% had a satisfactory result. Six
      feet required further surgery (reoperation rate of 23.1%).

PMID- 11324676
TI  - Low-molecular-weight heparin for deep vein thrombosis prophylaxis in foot and
      ankle surgery: a review.
AB  - The necessity of prophylaxis for deep vein thrombosis (DVT) in those patients who
      undergo foot and ankle surgery remains poorly defined. The authors explore and
      review the low-molecular-weight heparin (LMWH) preparations for use by foot and
      ankle surgeons. Recent literature has described a low incidence of DVT and
      pulmonary embolus (PE) following foot and ankle surgery. Nonetheless, it is
      paramount that foot and ankle surgeons be aware of the potential risk factors and
      methods of prophylaxis for DVT. Many options are available for prophylaxis. This
      article presents a review of DVT with particular attention given to
      distinguishing risk factors, prophylaxis, and LMWH preparations.

PMID- 11324677
TI  - Beta-blockers in the management of hypertension in patients with type 2 diabetes
      mellitus: is there a role?
AB  - It has been conclusively established that treatment of hypertension in patients
      with type 2 (non-insulin-dependent) diabetes mellitus will significantly reduce
      the incidence of stroke, heart failure and progression of diabetic complications.
      Beta-blockers are effective antihypertensive agents which, in long term studies,
      have proven beneficial in reducing important clinical end-points. However
      nonselective beta-blockers may have a negative effect on lipid profiles and
      contribute to hypoglycaemic unawareness, thus preventing their use in some
      patients with diabetes mellitus. The development of newer and more selective beta
      blockers has overcome many of these problems. In addition, some of the newer
      agents have novel properties such as release of nitric oxide, which theoretically
      would make them more attractive in patients with diabetes mellitus. Overall, the
      adverse metabolic effects of beta-blockers do not appear to be important in
      clinical practice and these agents should no longer be contraindicated in
      patients with type 2 diabetes mellitus. Their proven cardiovascular benefits
      would seem to easily tip the balance in favour of their use.

PMID- 11324678
TI  - Potential of microvascular reperfusion with adjunctive pharmacological
      intervention: its impact on myocardial perfusion and functional outcomes in
      patients with acute myocardial infarction.
AB  - One of the major limitations of reperfusion therapy in acute myocardial
      infarction (AMI) is the presentation of no-reflow phenomenon. In 25 to 30% of
      patients with AMI. myocardial blood flow is occasionally profoundly reduced, even
      after coronary recanalisation, because of microvascular dysfunction so-called no
      reflow phenomenon. Patients with this phenomenon are regarded as a high risk
      group among patients with reperfused AMI. Clinical studies using myocardial
      contrast echocardiography have demonstrated that intracoronary injection of
      calcium antagonists or potassium channel agonists in conjunction with coronary
      reperfusion can augment myocardial blood flow and that this was associated with
      better functional and clinical outcomes than with percutaneous transluminal
      coronary angioplasty alone. Thus, it is possible to prevent reperfusion injury
      and improve cardiac function using a adjunctive pharmacological intervention,
      either intravenously or by infusion directly into the coronary artery.

PMID- 11324681
TI  - Argatroban.
AB  - Argatroban is a direct thrombin inhibitor synthesised to bind to the catalytic
      site of the thrombin molecule. It binds rapidly and reversibly to both clot-bound
      and soluble thrombin. The relatively short elimination half-life of argatroban
      (39 to 51 minutes) and its reversible binding allow rapid achievement of
      therapeutic effect on initiation of therapy and rapid restoration of normal
      haemostasis upon cessation of therapy. Argatroban produces a predictable dose
      response that is well correlated with changes in anticoagulant parameters.
      Argatroban, given to patients with heparin-induced thrombocytopenia (HIT) and
      heparin-induced thrombocytopenia with thrombosis (HITTS) in a large scale,
      nonrandomised, prospective trial, reduced a combined end-point of morbidity and
      mortality when compared with historical controls. Argatroban was well tolerated
      in clinical trials of patients with HIT and caused no increase in bleeding risk
      compared with historical controls.

PMID- 11324680
TI  - Managing cancer-related anorexia/cachexia.
AB  - Cancer-related anorexia/cachexia (CAC) is a complex phenomenon in which metabolic
      abnormalities, proinflammatory cytokines produced by the host immune system,
      circulating tumour-derived catabolic factors, decreased food intake, and probably
      additional unknown factors, all play different roles. This review examines the
      mechanisms of CAC and its management. All the potential modalities of
      intervention from nutritional to pharmacological approaches are included with a
      clear distinction between unproven, investigational and well established
      treatments. Among the latter, the progestogens are currently considered the most
      effective and safest drugs for the management of CAC. Agents currently under
      investigation for CAC include thalidomide, pentoxifylline and melatonin, which
      most probably act on cytokine release, and clenbuterol, which acts on muscle mass
      and to antagonise protein wasting. Our personal experience with the synthetic
      progestogens megestrol and medroxyprogesterone supports their use as first-line
      agents. In addition, our work on the potential role of antioxidant agents in
      counteracting the oxidative stress, which appears to be involved in CAC, shows
      them to be promising agents when used in combination chemotherapy regimens either
      alone or with other 'biologics'. There is an ongoing need for quality of life
      questionnaires which specifically address the most significant symptoms present
      in patients with CAC.

PMID- 11324679
TI  - Review of macrolides and ketolides: focus on respiratory tract infections.
AB  - The first macrolide, erythromycin A, demonstrated broad-spectrum antimicrobial
      activity and was used primarily for respiratory and skin and soft tissue
      infections. Newer 14-, 15- and 16-membered ring macrolides such as clarithromycin
      and the azalide, azithromycin, have been developed to address the limitations of
      erythromycin. The main structural component of the macrolides is a large lactone
      ring that varies in size from 12 to 16 atoms. A new group of 14-membered
      macrolides known as the ketolides have recently been developed which have a 3
      keto in place of the L-cladinose moiety. Macrolides reversibly bind to the 23S
      rRNA and thus, inhibit protein synthesis by blocking elongation. The ketolides
      have also been reported to bind to 23S rRNA and their mechanism of action is
      similar to that of macrolides. Macrolide resistance mechanisms include target
      site alteration, alteration in antibiotic transport and modification of the
      antibiotic. The macrolides and ketolides exhibit good activity against gram
      positive aerobes and some gram-negative aerobes. Ketolides have excellent
      activity versus macrolide-resistant Streptococcus spp. Including mefA and ermB
      producing Streptococcus pneumoniae. The newer macrolides, such as azithromycin
      and clarithromycin, and the ketolides exhibit greater activity against
      Haemophilus influenzae than erythromycin. The bioavailability of macrolides
      ranges from 25 to 85%, with corresponding serum concentrations ranging from 0.4
      to 12 mg/L and area under the concentration-time curves from 3 to 115 mg/L x h.
      Half-lives range from short for erythromycin to medium for clarithromycin,
      roxithromycin and ketolides, to very long for dirithromycin and azithromycin. All
      of these agents display large volumes of distribution with excellent uptake into
      respiratory tissues and fluids relative to serum. The majority of the agents are
      hepatically metabolised and excretion in the urine is limited, with the exception
      of clarithromycin. Clinical trials involving the macrolides are available for
      various respiratory infections. In general, macrolides are the preferred
      treatment for community-acquired pneumonia and alternative treatment for other
      respiratory infections. These agents are frequently used in patients with
      penicillin allergies. The macrolides are well-tolerated agents. Macrolides are
      divided into 3 groups for likely occurrence of drug-drug interactions: group 1
      (e.g. erythromycin) are frequently involved, group 2 (e.g. clarithromycin,
      roxithromycin) are less commonly involved, whereas drug interactions have not
      been described for group 3 (e.g. azithromycin, dirithromycin). Few
      pharmacoeconomic studies involving macrolides are presently available. The
      ketolides are being developed in an attempt to address the increasingly prevalent
      problems of macrolide-resistant and multiresistant organisms.

PMID- 11324683
TI  - HLA transgenic mice as models of human autoimmune diseases.
AB  - MHC class II alleles have been linked to several human autoimmune diseases such
      as rheumatoid arthritis (RA), Type I diabetes, and multiple sclerosis (MS).
      Although the mechanisms by which expression of certain MHC class II molecules
      predispose an individual to a particular autoimmune disease are not known, it is
      clear that increased susceptibility is associated with the polymorphic regions
      unique to these predisposing HLA alleles. These polymorphic differences may
      influence susceptibility by selecting potential autoreactive T cells during
      thymic education. Alternatively, nonsusceptible alleles may either delete or fail
      to select these potential autoimmune T cells, thus reducing the possibility of
      developing disease. In the periphery, the unique specificity of the HLA molecule
      derived from a susceptible allele may then recognize and present an autoantigenic
      peptide or foreign peptide that may cross-react with an autoantigen, activating
      these autoreactive T cells and leading to disease. To dissect these possibilities
      and to determine the exact role of particular HLA-DR or DQ molecules in disease
      susceptibility, we have generated several lines of HLA-DR and DQ transgenic mice.
      In this review, we present data summarizing the functions of these HLA class II
      molecules using well-established mouse models for autoimmune diseases.

PMID- 11324682
TI  - Linezolid: a review of its use in the management of serious gram-positive
      infections.
AB  - Linezolid is the first of a new class of antibacterial drugs, the oxazolidinones.
      It has inhibitory activity against a broad range of gram-positive bacteria,
      including methicillin-resistant Staphylococcus aureus (MRSA), glycopeptide
      intermediate S. aureus (GISA), vancomycin-resistant enterococci (VRE) and
      penicillin-resistant Streptococcus pneumoniae. The drug also shows activity
      against certain anaerobes, including Clostridium perfringens, C. difficile,
      Peptostreptococcus spp. and Bacteroidesfragilis. In controlled phase III studies,
      linezolid was as effective as vancomycin in the treatment of patients with
      infections caused by methicillin-resistant staphylococci and also demonstrated
      efficacy against infections caused by VRE. Further phase III studies have
      demonstrated that linezolid is an effective treatment for patients with
      nosocomial pneumonia, for hospitalised patients with community-acquired
      pneumonia, and for patients with complicated skin or soft tissue infections
      (SSTIs). In these studies, linezolid was as effective as established treatments,
      including third-generation cephalosporins in patients with pneumonia, and
      oxacillin in patients with complicated SSTIs. Oral linezolid 400 or 600mg twice
      daily was as effective as clarithromycin 250mg twice daily or cefpodoxime
      proxetil 200mg twice daily in the treatment of patients with uncomplicated SSTIs
      or community-acquired pneumonia. Linezolid is a generally well tolerated drug.
      The most frequently reported adverse events in linezolid recipients were
      diarrhoea, headache, nausea and vomiting. Thrombocytopenia was also documented in
      a small proportion (about 2%) of patients treated with the drug. CONCLUSIONS:
      Linezolid has good activity against gram-positive bacteria, particularly
      multidrug resistant strains of S. aureus (including GISA), Enterococcus faecium
      and E. faecalis (including VRE). In controlled clinical trials, linezolid was as
      effective as vancomycin in eradicating infections caused by methicillin-resistant
      Staphylococcus spp. and has demonstrated efficacy against infections caused by
      VRE. As the level of resistance to vancomycin increases among S. aureus and
      enterococci, linezolid is poised to play an important role in the management of
      serious gram-positive infections.

PMID- 11324684
TI  - What transgenic and knockout mouse models teach us about experimental autoimmune
      encephalomyelitis.
AB  - Multiple sclerosis (MS) is a disease of the central nervous system with presumed
      autoimmune etiology. Experimental autoimmune encephalomyelitis (EAE), an
      inducible autoimmune disease in laboratory animals, is a widely accepted animal
      model of MS. Although it is well known that EAE is induced by autoreactive CD4+ T
      cells specific for myelin antigens, the demyelination process is manifested as a
      result of complex interactions among encephalitogenic, regulatory and accessory
      cell populations and factors produced by these cells. The outcome of the disease
      depends on which components become dominant. Examination of these components
      using genetically manipulated transgenic or gene-disrupted animal models has
      proved to be very useful. Here we examine the main processes leading to the
      development of EAE. The participation of different lymphocyte populations such as
      T, B cells or NK cells, as well as regulatory molecules and cytokines in the
      induction and regulation of EAE is discussed in the light of transgenic and
      knockout animal experiments. These animal models clearly show that autoimmune
      processes are regulated in a complex way, and that a given factor in this
      regulation can have very different effects according to the given
      microenvironment in which it acts.

PMID- 11324685
TI  - An approach to identify new genes in autoimmune diseases: lessons from rheumatoid
      arthritis.
AB  - We have searched the human genome for genes that predispose to rheumatoid
      arthritis using fluorescence-based microsatellite marker analysis and affected
      sib-pair linkage studies. A panel of 41 Japanese families, each with at least two
      affected siblings, was typed for genome-wide 358 polymorphic microsatellite
      marker loci. Three principal chromosome regions of linkage, D1S253/214, D8S556
      and DX1232, have been assigned, which we call RA1, RA2 and RA3 for rheumatoid
      arthritis disease loci. We are now assigning the death receptor 3 as a candidate
      gene for RA1, and the truncated form of Dbl proto-oncogene, which does not
      contain the 23rd and 24th exons, as disease gene for RA3. Microsatellite marker
      analyses seem to be promising and new genes are now being identified by reference
      to sequence tag sites.

PMID- 11324686
TI  - Genetic and immunological basis of autoimmune diabetes in the NOD mouse.
AB  - The non-obese diabetic (NOD) mouse is an animal model of human insulin-dependent
      diabetes mellitus (IDDM). Most NOD mice show insulitis at several weeks of age,
      and 60-90% of the female mice develop overt diabetes after 20-30 weeks of age.
      NOD mice share many features of human IDDM. As in human IDDM, the disease
      development in NOD mice is controlled by a number of disease susceptibility or
      resistant genes (Idds), including the major histocompatibility complex locus.
      Cumulative evidence suggests that Thl CD4+ T cells play a critical role in the
      autoimmune process leading to beta cell destruction. In addition to CD4+ T cells,
      CD8+ cells and B cells also participate in the pathogenesis. There are several
      candidate antigens recognized by autoreactive T cells such as glutamic acid
      decarboxylase (GAD), insulin and heat shock protein (HSP) 60. Treatment by these
      antigens suppresses IDDM development in NOD mice, suggesting that they may
      initiate the autoimmune process of NOD mice.

PMID- 11324687
TI  - Role of genetic factors in organ-specific autoimmune diseases induced by
      manipulating the thymus or T cells, and not self-antigens.
AB  - There are accumulating demonstrations that manipulation of the T-cell immune
      system, such as elimination of a particular T-cell subpopulation from the
      periphery or removal of the thymus during a critical neonatal period, can elicit
      activation/expansion of pathogenic self-reactive T cells from the remaining T
      cells and produce a wide spectrum of organ-specific autoimmune diseases in
      otherwise normal mice or rats. The genetic makeup of the hosts appears to play a
      key role in determining which self-reactive T-cell clones are prone to be
      activated under such circumstances, since a comparable degree of the immunologic
      abnormality elicits autoimmune disease in different spectrums of organs, with
      different incidences and severities, depending on the mouse or rat strains used.
      These findings indicate that one aspect of natural immunologic self-tolerance is
      maintained by a T cell-mediated control of potentially pathogenic self-reactive T
      cells in the periphery, and that defective control, caused by environmental
      insults or genetic abnormalities, suffices to cause autoimmune disease;
      furthermore, in the presence of such a T-cell abnormality, host genetic factors
      including MHC and non-MHC genes may determine the specificity and intensity of
      the autoimmune responses, and consequently the phenotype of the autoimmune
      disease.

PMID- 11324688
TI  - Genetic basis of autoimmune disease in MRL/lpr mice: dissection of the complex
      pathological manifestations and their susceptibility loci.
AB  - MRL/MpJ-lpr/lpr (MRL/lpr) mice spontaneously develop various forms of autoimmune
      disease in the same individuals, including glomerulonephritis, polyarteritis,
      arthritis and sialoadenitis. An MRL recombinant congenic strain of mice bearing
      the gld gene, MRLiMpTn-gld/gld (MRL/gld), also develops lesions similar to those
      in MRL/lpr mice. The lpr and gld genes are a Fas deletion mutant and a Fas ligand
      mutant, respectively. Thus, autoimmune disease in these mice seemed to be a
      single gene disease involving the complex pathological manifestations as
      pleiotropy. However, comparative studies with C3H/HeJ and C57BL/6J strains of
      mice bearing lpr or gld revealed that these lesions developed only in mice with
      an MRL background. Moreover, these lesions were genetically segregated among
      MRL/lpr x (MRL/lpr x C3H/lpr)F1 mice. This indicates that an MRL strain has
      particular gene(s) affecting the development of each lesion. Association studies
      of each lesion with polymorphic microsatellite markers using backcross mice
      revealed that gene loci responsible for each lesion exist at different
      chromosomal positions and have additive and hierarchical properties of polygenic
      inheritance for some of the lesions. We conclude that the complex pathological
      manifestations of autoimmune disease are under the control of different
      combinations of polygenes.

PMID- 11324689
TI  - B cell tolerance and autoimmunity.
AB  - Self-tolerance is induced in B cells at various maturational stages by diverse
      self-antigens B cell tolerance involves multiple mechanisms, ie. clonal deletion,
      clonal anergy, receptor editing and maturation arrest. The mechanism utilized for
      self-tolerance depends on both the maturational stage of B cells and the
      molecular nature of the self-antigens. B cell tolerance is abrogated by various
      mechanisms such as defects in inhibitory co-receptors, overexpression of CD19, T
      cell help and defects in the death receptor Fas (CD95). Since all of these
      molecules regulate B cell apoptosis mediated by either the antigen receptor or
      Fas, B cell apoptosis may play a role in the induction and maintenance of B cell
      tolerance. Moreover, environmental factors such as intestinal lipopolysaccharide
      also play a role in the breakdown of B cell tolerance.

PMID- 11324690
TI  - T cell tolerance and autoimmunity.
AB  - A functional immune system requires a T cell repertoire that is extremely diverse
      so as to allow for the elimination of all possible pathogens. However, the
      production of an immense T cell repertoire also increases the likelihood of
      generating autoreactive T cells. The immune system must therefore also
      incorporate a means of silencing or eliminating autoreactive T cells, while
      minimally sacrificing T cell diversity. The induction and maintenance of T cell
      unresponsiveness to self antigens is thus defined as T cell tolerance. This
      review provides an overview of the T cell tolerance mechanisms invoked in the
      thymus and in the periphery to prevent the induction of autoimmunity. Factors
      that can influence the induction of tolerance and autoimmunity are also
      discussed.

PMID- 11324691
TI  - The self-directed T cell repertoire: its creation and activation.
AB  - The considerable breadth of the self-directed T cell repertoire has only fully
      been appreciated during this past decade. It is a potential repertoire which can
      be tapped in various ways, most evidently in the study of autoimmune diseases,
      when because of a variety of factors, there is enhanced processing and
      presentation of determinants on self antigens. In this review, we have focused on
      the engagement of this self-reactive repertoire and some of the rules involved,
      which are not always so obvious. The total "residual" self-reactive repertoire
      directed against a single antigen (that remains after negative selection) will be
      a heterogeneous assemblage of T cells - (a) high affinity T cells directed
      against determinants whose presentation during tolerance induction was prevented,
      eg. through competitive binding by neighboring determinants; (b) lower affinity T
      cells directed against well-presented (dominant), as well as poorly-presented
      (cryptic) determinants; and (c) high affinity T cells directed against poorly
      presented determinants, which are only presented during inflammation. Under
      conditions that favor upregulation of previously cryptic self determinants, one
      or more of the above subsets of the 'protected' T cell repertoires can be
      stimulated by these self determinants, leading to induction of autoreactivity.
      The latter could eventually result in autoimmunity under permissive conditions
      governed by MHC and non-MHC genes. Interestingly, the very same repertoires that
      appear to be recruited into pathogenic autoimmune destruction may be
      alternatively manipulated as a source of anti-cancer treatment. It is now evident
      that many tumor antigens are unmutated self antigens, and cryptic determinants
      within such tumor antigens could be used to recruit the anticryptic T cell
      repertoire for induction of anti-tumor immunity.

PMID- 11324692
TI  - Activation of self-reactive B cells and autoimmune diseases.
AB  - The development of antigen-specific cells of the immune system, the T and B
      lymphocytes, creates a dilemma. On the one hand, survival of the organism depends
      upon the generation of a nearly limitless repertoire of potential antigen-binding
      specificities so that cells able to respond to pathogens are present prior to
      contact. However, by devising genetic strategies to maximize receptor diversity,
      the generation of T and B cells with autoreactive receptors is inevitable. B
      cells have an even greater opportunity than T cells to become autoreactive, since
      they may randomly alter the amino acid sequence and hence the specificity of
      their receptors during an immune response. Observing the system, one might wonder
      not why autoimmune diseases occasionally develop, but rather why they are not
      more frequent or even unavoidable. In this review, we examine the generation of B
      cells and their repertoire of antigen receptors, describe mechanisms that have
      evolved to prevent self-reactive B cells from causing autoimmune diseases, and
      discuss scenarios that may lead to a breakdown of self tolerance.

PMID- 11324693
TI  - Autoimmune lymphoproliferative syndromes (ALPS): models for the study of
      peripheral tolerance.
AB  - Lymphocyte cell death is a key event in the homeostasis of the immune system.
      Lymphocytes can be induced to die because of exposure to toxic agents, because of
      cytokine withdrawal or because specific cell surface receptors are engaged by
      their ligands. A number of such receptors belonging to the TNF receptor have been
      described in the recent past. Among these, the role of the Fas ligand/receptor
      interaction in the induction of lymphocyte cell death has been enlightened by the
      study of natural mutants, first described in mouse strains, then in humans. This
      review discusses the main findings provided by murine studies and clinical
      observations.

PMID- 11324694
TI  - Oral tolerance.
AB  - Oral administration of antigen results in immune tolerance which is mediated by
      anergy, deletion or the generation of regulatory cells, depending on the dose of
      antigen administered. Regulatory cells which secrete anti-inflammatory cytokines
      such as TGF-beta lead to bystander suppression at the target organ of the antigen
      fed. Oral administration of autoantigens has been shown to suppress autoimmune
      diseases in several animal models and is being tested as a potential therapy in
      human autoimmune and other inflammatory diseases.

PMID- 11324695
TI  - Role of costimulatory molecules in autoimmunity.
AB  - The precise mechanisms by which self-reactive T cells are activated and tolerance
      to self-antigens is broken are still not fully understood. It is widely accepted
      that dysregulation of costimulation contributes to the initiation and maintenance
      of autoimmunity due to activation of self-reactive T cells. Many of the
      costimulatory molecules thought to be essential for T cell activation have been
      identified. The CD28/CD152 (CTLA-4)-CD80/CD86 and CD40-CD154 (CD40 ligand)
      interactions are such receptor/ligand pairs that have been shown to be important
      in interactions between antigen-presenting cells and T cells. In vivo studies
      using costimulatory molecule-specific antibodies and fusion proteins and
      genetically manipulated animals have greatly increased our understanding of the
      role of these costimulatory molecules in the regulation of cellular processes
      that lead to autoimmunity and resultant autoimmune diseases.

PMID- 11324696
TI  - A molecule basis for the HLA association in rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a common chronic autoimmune disease that primarily
      affects the joints. The etiology of RA is unknown, and the pathogenesis is only
      poorly defined. One of the few clues to the understanding of the pathogenesis of
      RA is the observation that the disease is associated with genes in the major
      histocompatibility complex (MHC). Recent structural and functional studies
      provide molecular insight into the role of MHC genes in RA susceptibility. This
      insight provides an important basis for further understanding of the disease
      mechanism, generation of humanized animal models for RA, and the development of
      new immunomodulatory drugs with a minimum of unwanted side effects.

PMID- 11324697
TI  - Molecular aspects of HLA class II alphabeta heterodimers associated with IDDM
      susceptibility and protection.
AB  - HLA-DQ alleles are strongly associated with IDDM susceptibility and protection.
      Studies assessing the molecular properties of HLA-DR, a HLA class II locus in
      linkage disequilibrium with HLA-DQ, have made substantial contributions toward
      elucidating the structure and function of HLA class II molecules. Reports on the
      molecular properties of HLA-DQ are now following and have revealed interesting
      observations regarding the stability of HLA-DQ alphabeta heterodimers. Future
      work is expected to provide an understanding of the mechanism by which HLA-DQ is
      associated with IDDM susceptibility and protection.

PMID- 11324698
TI  - HLA, molecular mimicry and multiple sclerosis.
AB  - Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central
      nervous system in which an autoimmune response most probably contributes to
      pathogenesis. To date, the best characterized susceptibility-associated gene has
      been mapped to the HLA complex. The HLA-DRB1*1501 - DRB5*0101 - DQA1*0102 -
      DQB1*0602 haplotype is both associated and linked to MS in different ethnic
      groups. The locus within the HLA class II region encoding the MS-susceptibility
      gene is under intensive investigation. Epidemiological studies, however, have
      suggested that environmental antigens also play a critical role in MS
      pathogenesis. One of the ways a pathogen could trigger autoimmune disease is via
      immunological cross-reactivity or molecular mimicry. This concept argues that a
      microbial peptide with certain degree of homology to a self peptide can stimulate
      pathogenic self-reactive specific T cells to cause an autoimmune disease. Many
      microbial agents have regions of sequences that may serve as binding motifs for
      HLA-DR2. HLA genetics and molecular mimicry may therefore be intimately
      interlinked in the disease process. In the present review, we focus on the HLA
      association with MS and the role of microbial antigens in MS, with special
      reference to the molecular mimicry hypothesis.

PMID- 11324699
TI  - Lysophosphatidic acid synthesis and release.
AB  - Lysophosphatidic acid (LPA) is a bioactive phospholipid controlling numerous
      cellular responses through the activation of specific G-protein coupled
      transmembrane receptors. LPA is present in several biological fluids (serum,
      plasma, aqueous humor) and can be secreted by several cell types (platelets,
      fibroblasts, adipocytes, cancer cells). Whereas, multiple pathways of synthesis
      and degradation of LPA have been described, their relative contribution in
      extracellular secretion and biodisponibility is still a matter of debate. The
      first part of the present review is devoted to the description of the different
      enzymes involved in LPA synthesis (acyltransferases, phospholipases, kinases) and
      degradation (lysophospholipases, lipid-phosphatases), as well as to the molecules
      involved in LPA transport (albumin, fatty acid binding proteins, gelsolin,
      lipoproteins). In a second part, the different physio-pathological situations
      (aggregation, cancer, injuries) associated with LPA production, as well as the
      potential role played by LPA in genesis of certain diseases (cancer, obesity,
      arteriosclerosis) are listed and analyzed.

PMID- 11324700
TI  - Sphingosine 1-phosphate: synthesis and release.
AB  - Sphingosine 1-phosphate (Sph-1-P) is a bioactive sphingolipid, acting both as an
      intracellular second messenger and extracellular mediator, in mammalian cells. In
      cell types where Sph-1-P acts as an intracellular messenger, stimulation
      dependent synthesis of Sph-1-P, possibly resulting from sphingosine (Sph) kinase
      activation, is essential. Since this important kinase has recently been cloned,
      precise regulation of intracellular Sph-1-P synthesis will be clarified in the
      near future. As an intercellular mediator, elucidation of sources for
      extracellular Sph-1-P is important, in addition to identification of the cell
      surface receptors for this phospholipid. Blood platelets are very unique in that
      they store Sph-1-P abundantly (possibly due to the existence of highly active Sph
      kinase and a lack of Sph-1-P lyase) and release this bioactive lipid
      extracellularly upon stimulation. It is likely that platelets are an important
      source for extracellular Sph-1-P, especially for plasma and serum Sph-1-P.
      Platelet-derived Sph-1-P seems to play an important role in vascular biology.

PMID- 11324701
TI  - Pleiotypic mechanisms of cellular responses to biologically active
      lysophospholipids.
AB  - The activities of cell-derived lysophospholipid (LPL) growth factors on cellular
      proliferation and a range of proliferation-independent functions are regulated at
      multiple levels. This section focuses first on the capacity of the actin-severing
      protein gelsolin to bind lysophosphatidic acid (LPA), but not sphingosine 1
      phosphate (S1P), and either sequester LPA or present it to responsive cells.
      Expression of members of the family of endothelial differentiation gene-encoded G
      protein-coupled receptors (Edg Rs) for LPLs is controlled developmentally and by
      cell-activating stimuli. Edg R transduction of cellular effects of LPLs involves
      both direct actions on target cells and induction of generation of proteins with
      relevant actions capable of amplifying or diminishing primary direct effects of
      LPLs. These general mechanisms are evident in Edg R mediation of proliferation,
      cytokine secretion and suppression of apoptosis. The availability of functionally
      active anti-Edg R antibodies and Edg R-specific pharmacological probes,
      establishment of Edg R transgenes and gene knockouts, and identification of
      natural genetic anomalies of LPL metabolism and recognition by Edg Rs will permit
      elucidation of the in vivo activities of LPA and S1P normally and in disease
      states.

PMID- 11324702
TI  - Sphingosine kinase: a mediator of vital cellular functions.
AB  - Ample evidence indicates that sphingosine-1-phosphate (SPP) can serve as an
      intracellular second messenger regulating calcium mobilization, and cell growth
      and survival. Moreover, the dynamic balance between levels of the sphingolipids
      metabolites, ceramide and SPP, and consequent regulation of opposing signaling
      pathways, is an important factor that determines whether a cell survives or dies.
      SPP has also recently been shown to be the ligand for the EDG-1 family of G
      protein-coupled receptors, which now includes EDG-1, -3, -5, -6, and -8. SPP is
      thus a lipid mediator that has novel dual actions signaling inside and outside of
      the cell. This review is focussed on sphingosine kinase, the enzyme that
      regulates levels of SPP and thus plays a critical role in diverse biological
      processes.

PMID- 11324703
TI  - Sphingosine 1-phosphate receptors.
AB  - Sphingosine-1-phosphate (SPP) is a bioactive lipid produced from the metabolism
      of sphingomyelin. It is an important constituent of serum and regulates cell
      growth, survival, migration, differentiation and gene expression. Its mode of
      action has been enigmatic; however, recent findings have shown that a family of G
      protein-coupled receptors (GPCR) of the endothelial differentiation gene (EDG)
      family serve as plasma membrane-localized receptors for SPP. Furthermore, the EDG
      receptors appear to be SPP receptor subtypes with distinct signaling
      characteristics. In vascular endothelial cells, SPP acts on EDG-1 and EDG-3
      subtypes of receptors to induce cell survival and morphogenesis. Such pathways
      appear to be critical for SPP-induced angiogenic response in vivo. In addition,
      the EDG-1 gene is essential for vascular maturation in development. Moreover,
      developmental studies in Zebrafish have indicated that SPP signaling via the EDG
      5 like receptor Miles Apart (Mil) is essential for heart development. These data
      strongly suggest that a physiological role of SPP is in the formation of the
      cardiovascular system. Despite these recent findings, much needs to be clarified
      with respect to the physiological role of SPP synthesis and action. This review
      will focus on the recent findings on SPP receptors and the effects on the
      cardiovascular system.

PMID- 11324704
TI  - Sphingosine-1-phosphate phosphatases.
AB  - Sphingosine-1-phosphate is a potent proliferative, survival, and morphogenetic
      factor, acting as an extracellular ligand for the EDG family of G-protein-coupled
      receptors and possibly intracellularly through as yet, unidentified targets. It
      is produced within most, if not all cells by phosphorylation of sphingosine, and
      is an abundant serum lipid that is released from activated platelets. Sphingosine
      and sphingosine-1-phosphate are in dynamic equilibrium with each other due to the
      activities of sphingosine kinase and sphingosine-1-phosphate phosphatase
      (SPPase). Several SPPase genes have now been cloned, first from yeast and more
      recently from mammalian cells. By sequence homology, these enzymes can be
      classified as a subset of membrane bound, Type 2 lipid phosphohydrolases that
      contain conserved residues within three domains predicted to be at the active
      site of the enzyme. Outside of the consensus motif, there is very little homology
      between SPPases and the other type 2 lipid phosphohydrolases in the LPP/PAP
      family. Type 2 phosphatase activity is Mg+-independent and insensitive to N
      ethylmaleimide, and substrate specificity is broad for LPP enzymes, whereas
      SPPases are highly selective for sphingolipid substrates. SPPase activity in
      yeast and mammalian cells regulates intracellular sphingosine-1-phosphate levels,
      and also alters the levels of sphingosine and ceramide, two other signaling
      molecules that often oppose the actions of sphingosine-1-phosphate. Thus, loss of
      SPPase in yeast results in high sphingosine-1-phosphate levels and cells are more
      resistant to stress, and in mammalian cells, overexpression of SPPase elevates
      ceramide levels and provokes apoptosis.

PMID- 11324705
TI  - The LPA receptors.
AB  - Lysophosphatidic acid (LPA) is a growth factor-like lipid that produces many
      cellular responses. These responses, including actin cytoskeletal rearrangements,
      cell proliferation and inhibition of gap junction communication, have been
      documented in many cell types over the last 2 decades. Both non-receptor and
      receptor-mediated mechanisms had been implicated to explain these responses. A
      clear advance in this field was the cloning and functional identification of LPA
      receptors, and there are currently three high-affinity members, LPA1, LPA2 and
      LPA3 (synonymous with orphan receptor names edg-2, edg-4 and edg-7,
      respectively). Here we review the gene structure, expression and functions of LPA
      receptors. We also discuss the in vivo roles mediated by a single LPA receptor
      type, based on studies of the nervous system, a major locus of LPA receptor
      expression.

PMID- 11324706
TI  - Structure activity relationships of lysophospholipid mediators.

PMID- 11324707
TI  - Physiological responses to lysophosphatidic acid and related glycero
      phospholipids.
AB  - 1-Acyl-2-hydroxy(lyso)-sn-glycero-3-phosphate (lysophosphatidic acid, LPA) has
      attracted a lot of attention in recent years due to the wide range of its
      biological effects that span the phylogenetic tree from slime mold to human. LPA
      can be viewed as a pleiotropic phospholipid growth factor that utilizes the same
      signal transduction mechanisms as traditional polypeptide growth factors;
      however, LPA activates these mechanism via specific G protein-coupled receptors.
      The concentration of LPA in serum is in the high micromolar range, making it the
      most abundant mitogen/survival factor present in serum, one that is often
      unknowingly utilized in tissue culture. The present review gives a historical
      perspective and a critical analysis of the LPA literature with a special emphasis
      on the physiological implications of its effects.

PMID- 11324708
TI  - Lysophosphatidic acid and ovarian cancer: a paradigm for tumorogenesis and
      patient management.

PMID- 11324709
TI  - Lipid phosphate phosphatase-1 dephosphorylates exogenous lysophosphatidate and
      thereby attenuates its effects on cell signalling.
AB  - The serum-derived phospholipid growth factor, lysophosphatidate (LPA), activates
      cells through a family of G-protein-coupled EDG receptors. The present article
      examines the role of lipid phosphate phosphatase-1 (LPP-1, or phosphatidate
      phosphate 2A) in regulating cell activation by LPA. Overexpressing LPP-1
      approximately doubled the rate of dephosphorylation of exogenous LPA by Rat2
      fibroblasts. The amount of LPA dephosphorylation was restricted to less than 10%
      of the total exogenous LPA. Over-expression of LPP-1 attenuated cell activation
      as indicated by diminished responses including cAMP, Ca2+, activation of
      phospholipase D and ERK, DNA synthesis and cell division. LPP-1 therefore
      provides a novel level of regulation for controlling cell signalling by exogenous
      LPA.

PMID- 11324710
TI  - Modulation of cell interactions with extracellular matrix by lysophosphatidic
      acid and sphingosine 1-phosphate.
AB  - Lysophosphatidic acid (LPA) and sphingosine 1-phosphate (SPP) are lipid mediators
      released upon platelet activation. The concentration of LPA in serum is estimated
      at 1-10 microM whereas the concentration in plasma is considerably less. The SPP
      concentration in serum is 0.5 microM, approximately two-fold higher than the
      plasma concentration. The lipids are present during tissue injury and promote
      cellular processes involved in wound repair. LPA and SPP have multiple effects on
      cells, many of which are pertinent to wound healing and require that the cells
      interact in some fashion with components of the extracellular matrix. This review
      focuses on modulation of cell adhesion, cell migration, collagen gel contraction,
      and fibronectin matrix assembly by LPA and SPP.

PMID- 11324711
TI  - Steroidogenic correlates of pregnancy in the rock hyrax (Procavia capensis).
AB  - In pregnant rock hyraxes isolated leucocytes metabolise both [3H]pregnenolone and
      [3H]progesterone while whole blood, erythrocytes and an erythrocyte/leucocyte
      mixture only metabolised [3H]progesterone. Plasma displayed no tendency to
      metabolically convert any one of these two steroids. In whole blood
      [3H]progesterone appears to be converted to 5alpha-pregnane-3,20-dione and a
      compound with chromatographic properties similar to that of 5alpha-pregnan-3alpha
      ol-20-one. 5Alpha-pregnane-3,20-dione exhibited a high relative binding affinity
      for the uterine progesterone eceptor (94%), but 5alpha-pregnan-3alpha-ol-20-one
      displayed very little affinity for the same receptor (0.4%). 5Alpha-pregnane-3,20
      dione may therefore aid in the maintenance of pregnancy. Corpora lutea
      metabolised progesterone to 17alpha-hydroxyprogesterone, a compound exhibiting no
      progestational function because of its low relative binding affinity for the
      uterine progesterone receptor (2%). Progesterone appears to be the main product
      of the corpus luteum. However, 5alpha-pregnane-3,20-dione circulated at
      concentrations approximately 8.5 times higher than progesterone, probably due to
      the metabolic conversion of progesterone to 5alpha-pregnane-3,20-dione by the
      blood. We conclude that in the hyrax progesterone, produced by the corpora lutea,
      enters the circulation, where it is reduced to 5alpha-pregnanes. 5Alpha-pregane
      3,20-dione may then be transported to the uterus where it binds to the
      progesterone receptor to assist in the maintenance of pregnancy. This mechanism
      appears to be analogous to that of the African elephant which is phylogenetically
      related to the hyrax, except that in the elephant the 5alpha-reduced metabolites
      are produced by luteal tissue and not the blood.

PMID- 11324712
TI  - Determination of the levels of novel 31-amino acid endothelins and endothelins in
      human lungs.
AB  - An effective method for determination of the levels of newly discovered 31-amino
      acid endothelins [ETs(1-31)] as well as big ETs and 21-amino acid ETs [ETs(1
      21)], in human lungs has been developed. About 85% of ETs in human lung
      homogenates were recovered on acid extraction 8 times. Most of the published
      protocols for the determination of tissue ETs involve a reverse-phase minicolumn
      to separate proteins from peptides, after which the levels of ETs are directly
      determined by enzyme immunoassay. The levels determined, however, include fairly
      high amounts of non-bioactive ET metabolites in tissues and the data reported are
      diverse. We established an effective methods for the extraction and the
      separation of nine different muscle constricting ETs from their metabolites on a
      reverse-phase C18 column. Using this protocol, the levels of ETs in human lungs
      were determined by means of a sandwich-enzyme immunoassay specific for each ET
      derivative. The levels of ET-2(1-21) were the highest among those of ETs, and the
      levels of ETs(1-31) were in a similar range to those of big ETs but were lower
      than those of ETs(1-21). This method can be utilized to assess the
      pathophysiological roles of ETs(1-31) in various human organs.

PMID- 11324713
TI  - Induction of tumor necrosis factor receptor type 2 gene expression by tumor
      necrosis factor-alpha in rat primary astrocytes.
AB  - Using reverse transcription-polymerase chain reaction (RT-PCR) technique, the
      messenger RNA (mRNA) for tumor necrosis factor receptor type 2 (TNF-R2, 75/80
      kDa) was detected in rat primary astrocytes, with much lower level of expression
      when compared to that for tumor necrosis factor receptor type 1 (TNF-R1, 55/60
      kDa). Upon exposure to TNF-alpha (100 U/ml), the TNF-R2 mRNA level was greatly
      enhanced at 8 h, while TNF-R1 mRNA remained unchanged even after 24 h. The
      induction of TNF-R2 gene expression by TNF-alpha was dose-dependent and seemed to
      be unique to TNF-alpha, as interleukin-6 (IL-6) had no significant effect on TNF
      R2 expression. Since TNF-R2 was reported to mediate mitogenic and gene-inducing
      effects in many other cell types, it is likely that the reported proliferative
      effect of TNF-alpha on astrocytes was also mediated by this TNF receptor subtype.
      Upon exposure to TNF-alpha or lipopolysaccharide (LPS), the expression of TNF
      alpha gene was induced, and the LPS-induced TNF-alpha seemed to selectively
      enhance the TNF-R2 gene expression. Collectively, our results suggest that the
      TNF-alpha or LPS-induced expression of both TNF-R2 and TNF-alpha may provide a
      positive control mechanism to further enhance the proliferative effect of TNF
      alpha in astrocytes.

PMID- 11324714
TI  - Exploration of the awakening cortisol response in relation to diurnal cortisol
      secretory activity.
AB  - Adrenocortical activity can be assessed by measurement of free cortisol in
      saliva. Cortisol status has important health implications in both physical and
      psychological terms. Assessment of cortisol status is complicated by the marked
      diurnal cortisol cycle. This cycle is characterised by an increase in secretory
      activity following awakening to achieve the morning acrophase. Thereafter it
      falls with a declining trend over the remainder of the day. For between subject
      studies the timing of sampling in relation to this cycle is an important
      consideration. We report a comprehensive study of the diurnal free cortisol cycle
      designed to analyse its components and to investigate their reliability and inter
      relatedness. We instructed 42 healthy volunteers to collect saliva samples at
      home on two consecutive days. On each day the first sample was collected
      immediately upon awakening, followed by a further three samples at 15-minute
      intervals which collectively comprised the "awakening samples". A further four
      sample's were collected through the day at 3-hour intervals, all synchronized to
      awakening time. The cortisol response to awakening was calculated in two ways.
      Overall cortisol production in the first 45 minutes after awakening was
      calculated as area under the cortisol curve with reference to zero (AUC). The
      dynamic of the cortisol response to awakening was calculated as area under the
      cortisol response curve (AURC) with reference to the first awakening sample. In
      addition the underlying cortisol secretory activity was assessed based upon the
      diurnal three-hourly samples. All three parameters of adrenocortical activity
      showed reasonable stability across the two sampling days indicating all were
      reliable indexes of trait characteristic. AUC was representative of underlying
      diurnal activity but AURC was not. Measurement at any time point, 3, 6, 9 or 12
      hours post-awakening was representative of the underlying 12-hour diurnal
      activity.

PMID- 11324715
TI  - Ultrastructural and functional changes in the jejunal epithelium of spontaneously
      hypertensive rats.
AB  - Ultrastructural studies on the epithelium, sugar transport and
      immunocytochemistry of Na+-glucose cotransporter (SGLT1) were carried out in the
      jejunum of Spontaneously Hypertensive Rats (SHR) and their normotensive genetic
      control, Wistar-Kyoto (WKY) rats. Electron microscopy studies showed a regular
      brush-border membrane in the jejunal enterocytes of WKY rats, with colloidal gold
      particles, representing SGLTI, localized at the microvilli of the absorptive
      epithelial cells. However, a patchy loss of microvilli was detected in the
      jejunal sections from SHR, with no presence of colloidal gold particles,
      indicating the absence of the SGLT1 protein. Most adjacent microvilli were normal
      in size like those found in WKY rats, and SGLT1 labeling was observed. All these
      changes were accompanied by a reduction in Na+-dependent D-glucose and D
      galactose uptakes in the jejunal BBMVs isolated from SHR, when compared to WKY
      rats. We conclude that ultrastructural changes were paralleled by modifications
      in the sugar transport and in the localization of SGLT1 in the jejunal epithelium
      of SHR.

PMID- 11324716
TI  - Lithium does not synergize the peripheral action of cholinomimetics as seen in
      the central nervous system.
AB  - Lithium is known to synergize the action of cholinomimetics in the CNS such that
      pilocarpine induces seizures in low concentration (1/13th of per se dose) in
      rats. The present study was undertaken to see if lithium priming also enhances
      the peripheral effects of acetylcholine and pilocarpine i.e. change in blood
      pressure in rats and contractions of the isolated guinea pig ileum. In
      anaesthetized rats the blood pressure was recorded from cannulated carotid artery
      connected through the pressure transducer to Coulbourn polygraph. The blood
      pressure response of pilocarpine was not different either in magnitude or in
      duration when administered 1, 2 and 4 h after lithium chloride (3 meq/kg)
      pretreatment as compared to the control. Similarly acetylcholine effect remained
      unchanged after lithium chloride priming. In the isolated guinea pig ileum
      experiments, ileum was incubated for 1 h in different concentrations of lithium
      chloride and effect on acetylcholine induced contractions were observed. Lithium
      in concentration of 2.8 x 10(-3) M had no effect on acetylcholine induced
      contractions while incubation with higher concentrations of 1.4 x 10(-2) M and
      2.8 x 10(-2) M significant inhibition of acetylcholine contractions were
      observed. At this concentration, histamine induced contractions were also
      inhibited. The results indicate that lithium does not synergize the action of
      cholinomimetics in the periphery as that seen in the CNS. The inhibition of
      acetylcholine and histamine induced contractions in guinea pig ileum at high
      concentration of lithium seems to be non-specific effect.

PMID- 11324717
TI  - The effects of norepinephrine and prostaglandin E1 on pharmacokinetics of
      lidocaine in isolated perfused rat liver.
AB  - We hypothesized that depression of liver function by norepinephrine can be
      improved by prostaglandin E1. Isolated perfused rat liver was selected as an
      experimental model, since the flow rate can be regulated in it. Twenty-one rats
      were randomly allocated to three groups: control, norepinephrine, and
      norepinephrine and prostaglandin E1 groups. The liver was perfused in a
      recirculating system at a constant flow rate of 20 ml/min. After administration
      of two milligrams of lidocaine in each group, lidocaine and
      monoethylglycinexylidide concentrations in the recirculating system were
      measured. Lidocaine pharmacokinetics were analyzed using the SAAM II program,
      including metabolic rate from lidocaine to monoethylglycinexylidide using time
      concentration curves. Norepinephrine significantly increased perfusion pressure
      and the area under the time-concentration curve for lidocaine. Norepinephrine
      decreased the clearance and the elimination rate constant of lidocaine compared
      with those in the control group. Although administration of prostaglandin E1
      after infusion of norepinephrine did not significantly change perfusion pressure,
      it significantly (p < 0.05) improved metabolic rate, clearance and the
      elimination rate constant of lidocaine in the isolated rat liver model.

PMID- 11324718
TI  - cDNA cloning and expression of a bovine phenol UDP-glucuronosyltransferase,
      BovUGT1A6.
AB  - A full-length cDNA encoding a phenol UDP-glucuronosyltransferase was isolated by
      plaque hybridization, RT-PCR and 5'-RACE from a cDNA library prepared from the
      bovine liver. The deduced amino acid sequence (529 amino acid residues) has A
      signal sequence (23 amino acid residues) at the amino terminus and a
      transmembrane-anchoring domain (17 amino acid residues) at the carboxyl terminus.
      The encoded protein has a potential asparagine-linked glycosylation site
      (Asn291). The cloned cDNA was named bovUGT1A6 on the basis of the amino acid
      similarity. BovUGT1A6 cloned in the pAAH5 expression vector was transformed into
      Saccharomyces cerevisiea AH22 cells to obtain an active 54-kDa bovUGT1A6 enzyme.
      The expressed enzyme represented UDP-glucuronosyltransferase activities toward 1
      naphthol and 4-methylumbelliferone, confirming that the isolated cDNA is an
      isoform of bovine phenol UDP-glucuronosyltransferase. Microsomal UDP
      glucuronosyltransferase activity toward 1-naphthol in the bovine kidney cortex
      was found to be higher than that in the liver and other organs, and mRNA of
      bovUGT1A6 was more strongly detected in the kidney on Northern blotting analysis.
      These results suggest that the bovine kidney, which strongly expresses bovUGT1A6,
      is a significant organ for xenobiotics glucuronidation.

PMID- 11324719
TI  - Serum induces a transcriptional activation of CYP1A1 gene in HepG2 independently
      of the AhR pathway.
AB  - CYP1A1 is largely implicated in carcinogenesis. To date, it is known that this
      gene is induced by xenobiotics such as polycyclic aromatic hydrocarbons. In this
      study, we evaluated the effect of serum in the regulation of CYP1A1 gene
      expression. CYP1A1 mRNA level is induced 1) in HepG2 and HT29-D4 cells by 3
      methylcholanthrene 2) only in HepG2 after treatment by serum. The CYP1A1 mRNA
      induction in HepG2 is the consequence at least in part of a transcriptional
      activation as was demonstrated by evaluation of the hnRNA level. HepG2 cells were
      transfected by a plasmid containing the 7.5 Kb of the CYP1A1 promoter and the CAT
      reporter gene. No CAT stimulation was observed after serum treatment. These
      results demonstrated that CYP1A1 is induced at a transcriptional level by a
      physiological compound contained in serum independently of the Ah receptor and
      the 7.5 Kb promoter region.

PMID- 11324720
TI  - Isolation and characterization of velutin, a novel low-molecular-weight ribosome
      inactivating protein from winter mushroom (Flammulina velutipes) fruiting bodies.
AB  - From the fruiting bodies of the edible mushroom Flammulina velutipes a single
      chained ribosome inactivating protein with a molecular weight of 13.8 kDa was
      isolated with a procedure involving ion exchange chromatography on DEAE-cellulose
      and SP-Sepharose and affinity chromatography on Affi-gel blue gel. The protein
      was novel in that it possessed a molecular weight lower than those of previously
      reported RIPs and that it was capable of inhibiting human immunodeficiency virus
      (HIV-1) reverse transcriptase, beta-glucosidase and beta-glucuronidase. Its N
      terminal sequence exhibited a certain degree of similarity to those of plant
      ribosome inactivating proteins.

PMID- 11324721
TI  - Nebivolol and airway responsiveness in the rabbit.
AB  - Beta-adrenergic receptor antagonists are currently used as first-line therapy in
      the treatment of hypertension and angina pectoris, but are contraindicated or
      used with caution in patients with bronchospastic syndromes. In this study we
      evaluated in vivo the effects of nebivolol on airway responsiveness compared to
      atenolol, pindolol, and propranolol. In New Zealand white rabbits total lung
      resistance (R(L)) and dynamic compliance (Cdyn) were calculated. In acute
      protocol, the animals were intravenously injected with the beta-blockers at
      different doses while in the chronic protocol, animals were daily injected for 30
      days. Furthermore, the changes induced by beta-blockers (higher doses) in R(L)
      and Cdyn after a treatment with salbutamol were calculated. In acute treatment,
      airway responsiveness to histamine was not modified by nebivolol at any dosage,
      but increased significantly following the exposure to the higher doses of the
      other beta-blockers. In chronic treatment, the thirty-day exposure to nebivolol,
      did not modify the airway responsiveness to histamine, whereas the other beta
      blockers significantly increased airway responsiveness. Moreover, nebivolol
      affected the salbutamol-induced relaxation less markedly than other beta-blockers
      do. These data demonstrate that nebivolol respect the other beta-blockers used in
      this study, does not significantly affect the airway responsiveness, therefore it
      could be used in patients with both cardiovascular and bronchial diseases more
      safely than other beta-blockers drugs.

PMID- 11324722
TI  - Differential display reveals downregulation of the phospholipid transfer protein
      (PLTP) at the mRNA level in brains of patients with Down syndrome.
AB  - The phospholipid transfer protein (PLTP) shows a wide variety of functions
      including transfer of phospholipids and other lipid-like substances. Performing
      gene hunting in brain of patients with Down syndrome (DS) we detected the absence
      of a fragment identified as PLTP. Cerebellum of 4 controls, 7 patients with DS, 5
      patients with Alzheimer's disease (AD) were used for differential display and for
      quantification of mRNA steady state levels of the isomer PLTP-1 by blotting
      methods. Differential display showed the absence of a cDNA fragment and cloning,
      sequencing and gene bank work revealed 100% homology with human PAC 337018 on
      chromosome 20q containing the PLTP gene. The PLTP gene in turn consists of at
      least three different PLTP-isomers. Based on these results, a 450 bp cDNA
      fragment of the PLTP-isomer I (PLTP I) was isolated and amplified by PCR, serving
      as probe for the PLTP-1 isomer and its expression level was found to be
      significantly reduced in cerebellum of patients with DS. Biologically, the
      downregulation of PLTP maybe involved in the pathology of DS as phospholipids not
      only are of importance for membrane biogenesis and structure but also in the
      regulation of cellular metabolism, signaling and growth. In the brain,
      phospholipids in addition are integral constituents of myelins and synaptosomes
      (Johnson etc) and deficient PLTP levels may account for the deteriorated
      functions described to occur in DS brain.

PMID- 11324723
TI  - Guanylin family: new intestinal peptides regulating electrolyte and water
      homeostasis.
AB  - The regulation of intestinal salt and water transport is critical to the
      maintenance of fluid volume. Control of this life-sustaining activity is mediated
      by the concerted actions of hormones, neurotransmitters, and locally acting
      factors. Guanylin and uroguanylin are novel peptides that were first isolated
      from rat jejunum and opossum urine, respectively. They bind to and activate
      guanylyl cyclase-C (GC-C) receptors to regulate intestinal and renal fluid and
      electrolyte transport through the second messenger, cyclic guanosine 3',5'
      monophosphate (GMP). Heat-stable enterotoxins produced by pathogenic bacteria
      have close structural similarities to guanylin and uroguanylin, and they use this
      mimicry to act on GC-C, causing life-threatening secretory diarrhea. Guanylin
      primarily is restricted to the intestine, whereas uroguanylin is present in the
      stomach, kidney, lung, and pancreas, in addition to intestine. Guanylin and
      uroguanylin are secreted into the intestinal lumen and blood in response to
      sodium chloride administration. These peptides function in salt and water
      transport in the intestine and kidney by luminocrine and endocrine actions. The
      guanylin family is involved in the pathophysiology of some gastrointestinal,
      renal, and heart diseases.

PMID- 11324724
TI  - Relationship between severity of reflux esophagitis according to the Los Angeles
      classification and esophageal motility.
AB  - PURPOSE: We investigated the relationship between the severity of reflux
      esophagitis (RE) according to the Los Angeles (LA) classification and esophageal
      motility. METHODS: We examined 28 healthy subjects (HS) and 48 RE patients (grade
      A of the LA classification, 16 patients; grade B, 16 patients; grade C or D, 16
      patients). Esophageal manometry was performed by the intraluminal microtransducer
      method. Resting lower esophageal sphincter (LES) pressure was assessed by the
      rapid pull-through method. Esophageal contraction after ten repeated 5-ml water
      swallowings separated by 30-s intervals was measured at 3, 8, 13, and 18 cm above
      the LES. RESULTS: The resting LES pressure and the amplitude of esophageal
      contraction 3 cm above the LES in the grades C + D group were significantly lower
      than those in the HS group. The amplitude of esophageal contraction 3 cm above
      the LES in the grade B group was significantly lower than those in the grade A
      group and the HS group. The frequency of failed peristalsis in the grades C + D
      group was significantly higher than that in the HS group and the grade A and
      grade B groups. CONCLUSIONS: The present findings suggested that the severity of
      RE according to the LA classification would be likely to mainly reflect
      esophageal volume clearance.

PMID- 11324725
TI  - Effect of carnitine on stress-induced lipid peroxidation in rat gastric mucosa.
AB  - PURPOSE: Carnitine is an essential cofactor in the mitochondrial transfer of
      fatty acids, but is also a scavenger of oxygen free radicals in mammalian
      tissues. It has been shown that cold-restraint stress (CRS) produces gastric
      mucosal injury due to oxygen free radicals. The aim of this study was to
      determine the effect of L-carnitine on lipid peroxidation induced by CRS in rat
      stomachs. METHODS: Rats pretreated with L-carnitine (50 mg/kg per day for 10
      days) were restrained in a wire cage for 4 h at 4 degrees C. At the end of the
      experimental period, the lesion index in gastric mucosa was determined. In blood
      and gastric mucosa samples, the content of mucin, prostaglandin (PG)E2, the
      products of lipid peroxidation, and catalase activity were measured. RESULTS: CRS
      caused a significant decrease in gastric mucin and PGE2 content, while in the
      gastric mucosa of rats pretreated with L-carnitine, the changes in gastric mucin
      and PGE2 content, as well as gastric lesion development and enhanced lipid
      peroxide formation due to stress, were prevented. On the other hand, catalase
      activity in blood increased in the CRS group, while its value in gastric mucosa
      was not different from that in the control rats. L-Carnitine treatment increased
      catalase activity in both blood and gastric mucosa in control animals. Following
      stress, increased catalase activity of blood was associated with decreased
      mucosal catalase activity in rats that received L-carnitine. CONCLUSIONS: L
      Carnitine prevents the occurrence of mucosal lesions by strengthening the gastric
      mucosal barrier and by reducing the products of lipid peroxidation against
      noxious factors that cause elevation of lipid peroxidation, such as CRS.

PMID- 11324726
TI  - An efficient method for the culture of Helicobacter pylori from gastric biopsies
      with two-section petri dishes.
AB  - PURPOSE: Helicobacter pylori is the principal cause of chronic gastritis and is
      strongly associated with peptic ulcer disease and gastric cancer, as well as with
      gastric lymphoma (mucosa-associated lymphoid tissue [MALT] type). H. pylori could
      be recovered by many kinds of media, however, it could not be detected
      efficiently. This study was trying to ameliorate the isolation and detection rate
      with selective and non-selective media. METHODS: First, type strain (ATCC 43504)
      was cultured with twelve different kinds of sheep blood agar based on brain heart
      infusion medium for five days. Then five better non-selective media and five
      selective media were chosen for the biopsy, which were incubated at 37 degrees C
      in a microaerophilic incubator for five days. Endoscopic biopsies were collected
      from 623 patients at Kaohsiung Medical University Hospital. RESULTS: It was found
      that non-selective media, which contain 5% modified chocolate agar (the ratio of
      fresh and heated sheep blood is 2) with 1% Isovitalex, had the best detection
      rate (91.1 +/- 0.6)%. Furthermore, 5% modified chocolate agar with 1% Isovitalex
      and 1% antibiotics would increase the detection rate to (97.1 +/- 0.3)%.
      CONCLUSIONS: According to Ansorg's method, the best detection rate (98.4 +/-
      0.7)% could be obtained with two-section petri dishes which had 5% modified
      chocolate agar with antibiotics and the other without antibiotics.

PMID- 11324727
TI  - Twice-daily administration of interferon-beta for chronic hepatitis C is not
      superior to a once-daily regimen.
AB  - PURPOSE: Although interferon (IFN) is commonly used for the treatment of chronic
      hepatitis C virus (HCV) infection, eradication of the virus occurs in only a
      small proportion of patients with genotype 1b and a high virus titer. Modified
      IFN therapies have been tried, with only limited benefit. Recently, the
      administration of IFN-beta twice per day has been reported to be more effective
      than the usual once-daily administration regimen. The aim of this study was to
      evaluate whether twice-daily IFN results in a sustained response in patients with
      chronic HCV infection with genotype 1b, and a high virus titer. METHODS: Twenty
      patients with genotype 1b and high HCV RNA level (more than 1 MEq/ml by branched
      DNA probe assay) were randomly assigned to receive either twice-daily 3 MU of IFN
      beta (group A) or once-daily 6 MU of IFN-beta (group B) for 4 weeks. All patients
      received a further daily dose of 6 MU IFN-beta for 12 weeks, followed by IFN-alfa
      three times a week for 16 weeks. RESULTS: Although a rapid fall in HCV RNA levels
      was noted in group A, a sustained response was observed in only one of nine
      patients in this group, and none of group B. Adverse effects of IFN were more
      frequent and pronounced in group A than in group B. CONCLUSIONS: We conclude that
      further modification, which combines the early strong anti-viral effects of the
      twice-daily regimen with long-term sustained response, is necessary for effective
      therapy of HCV patients with genotype 1b and high HCV RNA levels.

PMID- 11324728
TI  - The follow-up of asymptomatic persons with antibodies to pyruvate dehydrogenase
      in adult population samples.
AB  - PURPOSE: The presence of antimitochondrial antibodies (AMA), the hallmark of
      primary biliary cirrhosis (PBC), precedes the clinical manifestation of the
      disease for many years. The main mitochondrial autoantigen is the E2 component of
      the pyruvate dehydrogenase complex (PDC). The aim of this study was to identify
      anti-PDC-positive persons from two Estonian populations by different
      methodologies and to follow up the positive cases. METHODS: Enzyme-linked
      immunosorbent assay (ELISA) tests for antibodies to native PDC and recombinant
      PDC-E2 fusion protein were performed in 1461 persons (age range, 15-95 years)
      from Karksi-Nuia (plus 104 volunteers from the neighborhood) and to native PDC in
      497 persons (age range, 50-91 years) from Abja-Paluoja (plus 28 volunteers from
      that neighborhood). Positive cases were tested with an enzyme inhibition assay.
      RESULTS: We identified 14 asymptomatic persons with antibodies to native PDC
      and/or recombinant PDC-E2 from these two population samples. Eight of the 14 were
      available for follow-up. Three of the 8 developed abnormal liver biochemical test
      results by the ninth year of follow-up. These persons also had, or developed,
      during the follow-up, a positive AMA immunofluorescence test, inhibitory
      antibodies to PDC, and anti-PDC of at least IgG and IgA class. Five of the 8
      persons with low levels of anti-PDC, of only one immunoglobulin class reacting
      with only one PDC preparation, did not show any signs of cholestasis or changes
      in their immunoreactivity during follow-up. CONCLUSIONS: A significant number of
      asymptomatic patients found to have antibodies to PDC are at high risk of
      developing primary biliary cirrhosis.

PMID- 11324729
TI  - Endoscopic therapy with absolute ethanol for postoperative recurrent ulcers in
      intestinal Behcet's disease, and simple ulcers.
AB  - BACKGROUND: When examined macroscopically and histologically, there are no
      differences between "simple" intestinal ulcers and intestinal ulcers of Behcet's
      disease. The postoperative recurrence of intestinal Behcet's disease and simple
      ulcers was frequently. Medical treatment for postoperative recurrent ulcers is
      palliative, and the patient often requires surgery. We studied about an effect of
      absolute ethanol spraying via endoscopy for the ulcers. METHOD: The postoperative
      rate of recurrence was 56% (9/16). Commonly the ulcer recurred around the
      anastomotic region. We performed spraying for recurrent ulcers with absolute
      ethanol via endoscope in four patients. RESULTS: This therapy was effective for
      the recurrent ulcer in the 4 patients. In this study, the patients who were
      monitored and treated by the spraying of ethanol did not require further surgery.
      CONCLUSIONS: This therapy should performed for recurrent ulceration in cases of
      simple ulcer and intestinal Behcet's disease.

PMID- 11324730
TI  - A squamous cell carcinoma of the gastric cardia showing submucosal progression.
AB  - We report a case of squamous cell carcinoma (SCC) of the gastric cardia showing
      submucosal progression with direct invasion of the liver. A 71-year-old man was
      admitted with dysphagia. Esophagogastroscopy showed a protruding tumor covered
      with normal gastric mucosa in the anterior wall of the gastric cardia, although
      no abnormal findings were detected in the esophagus, including the
      esophagogastric junction. Serum SCC-related antigen level was elevated (6.6
      ng/ml; normal level, less than 2.5 ng/ml). Endoscopic biopsy specimens taken from
      this tumor did not show malignant cells. Based on these findings, the
      preoperative diagnosis was a submucosal tumor of the stomach. Laparotomy was
      done; however, the tumor was not resected because it had direct invasion to the
      left lateral segment of the liver and adjacent tissues. As the tumor showed
      continuous bleeding from the stomach after surgery, total gastrectomy, combined
      with transhiatal lower esophagectomy, left lateral segmentectomy of the liver,
      splenectomy, and distal pancreatectomy was performed. Because histologic findings
      showed poorly or moderately differentiated SCC with direct invasion of the liver,
      the final diagnosis was SCC of the gastric cardia showing submucosal progression
      with hepatic invasion. Such a case of SCC of the gastric cardia showing
      submucosal progression is rare, and accurate preoperative diagnosis was very
      difficult. However, it may be important to consider SCC of the gastric cardia in
      such a situation.

PMID- 11324731
TI  - Microscopic polyangiitis complicated with massive intestinal bleeding.
AB  - Microscopic polyangiitis (MPA) is associated with renal dysfunction, in most
      cases, and occasionally with pulmonary hemorrhage. However, massive intestinal
      bleeding is a rare manifestation. We report a case of MPA in a man who developed
      arterial bleeding in the small intestine. A 74-year-old man was admitted after
      enduring a fever for 4 weeks. Laboratory examination revealed leucocytosis with
      neutrophil predominance, and renal dysfunction was noted. He did not respond to
      treatment with antibiotics, and the worsened renal function soon required
      hemodialysis. On the seventh hospital day, he suddenly developed massive melena.
      A colonoscopic examination suggested bleeding in the small intestine, and
      abdominal angiography demonstrated that the bleeding originated in a branch of
      the ileal artery. Hemostasis was achieved by transarterial embolization (TAE),
      but the patient suffered a massive pulmonary hemorrhage 2 days after the TAE.
      Although he responded well to a combination treatment with corticosteroid and
      cyclophosphamide, recurrence of pulmonary hemorrhage led to death, on the 87th
      hospital day. MPA in this patient was associated with three serious
      complications; deteriorating renal function, massive melena, and pulmonary
      hemorrhage. Of the various manifestations associated with MPA, arterial bleeding
      in the gastrointestinal tract, although rare, should be considered as one of the
      serious complications in MPA.

PMID- 11324732
TI  - Hepatic peribiliary cysts diagnosed by magnetic resonance cholangiography.
AB  - We report a 76-year-old man with hepatic peribiliary cysts diagnosed by magnetic
      resonance cholangiopancreatography (MRCP). On his first admission, in 1991, the
      patient was misidentified as having localized dilatation of the left intrahepatic
      bile ducts, from the ultrasound (US) and computed tomographic (CT) findings, or
      primary sclerosing cholangitis from endoscopic retrograde
      cholangiopancreatography (ERCP). However, US and CT in 1998 suggested worsening
      of the lesions. MRCP was performed for the first time, revealing hepatic
      peribiliary cysts in the hepatic hilum and along the left hepatic ducts. Drip
      infusion cholangiography (DIC)-CT confirmed the extraluminal compression of the
      bile ducts, caused by the cysts, without an influx of contrast medium into the
      hepatic peribiliary cysts. Retrospective evaluation showed increases in the size
      and number of the cysts in 1998 compared with the findings in 1996.

PMID- 11324733
TI  - Carcinoma of the cystic duct associated with pancreaticobiliary maljunction.
AB  - We report a rare case of carcinoma of the cystic duct (CCD) associated with
      pancreaticobiliary maljunction (PBM). A 63-year-old man had presented with
      relapsing cholecystitis of 4 months, duration. Computed tomography showed a
      distended gallbladder: however, small mass in the cystic duct was overlooked.
      Endoscopic retrograde cholangiopancreatography demonstrated a long common channel
      (20-mm-long) and fusiform dilatation of the common bile duct, findings, which
      were consistent with PBM. At laparotomy, we found a papillary tumor, 20 mm in
      diameter, that obstructed the cystic duct. The patient underwent resection of the
      gallbladder and the common bile duct, lymph node dissection in the hepatoduodenal
      ligament, and hepaticojejunostomy. Histologic study revealed a papillary
      adenocarcinoma confined within the subserosal space. There was no lymphatic or
      perineural invasion of cancer cells. The surrounding cystic ductal mucosa showed
      dysplasia and hyperplasia, and the gallbladder and common bile duct showed severe
      inflammation. The patient has been doing well for 16 months after surgery,
      without tumor recurrence. This case suggests a relationship between CCD and
      chronic biliary inflammation caused by PBM, as in cases of gallbladder carcinoma.

PMID- 11324734
TI  - How to improve virological sustained response rate by interferon therapy for
      patients with chronic hepatitis C.

PMID- 11324735
TI  - Is anti-pyruvate dehydrogenase complex a predictor of the development of primary
      biliary cirrhosis?

PMID- 11324736
TI  - Hepatic peribiliary cysts: clinically harmless disease with potential risk due to
      gradual increase in size and number.

PMID- 11324737
TI  - Primary carcinoma of the cystic duct associated with pancreaticobiliary
      maljunction.

PMID- 11324738
TI  - Why do delays in treatment occur? Lessons learned from ruptured appendicitis.

PMID- 11324739
TI  - Patterns of mental health utilization and costs among children in a privately
      insured population.
AB  - OBJECTIVE: To examine trends in mental health service use and cost among
      privately insured children. DATA SOURCES: Inpatient and outpatient claims from
      the MarketScan database, a collection of health care claims for a national sample
      of over seven million privately insured individuals. Claims were analyzed for all
      users of mental health services 17 years of age and under from 1993 to 1996.
      STUDY DESIGN: The proportion of children receiving mental health services and
      annual costs and treatment days per treated child were compared across diagnostic
      groups over time. PRINCIPLE FINDINGS: The proportion of covered children
      receiving any mental health services fell substantially (-30.0 percent).
      Inpatient mental health costs per treated child fell $4,587 (-46.9 percent)
      during the period, driven by decreases in the number of hospital days per treated
      child per year (-22.9 percent) and per diem costs (-14.5 percent). Outpatient
      mental health costs also fell during the period due to a 5.1 percent decline in
      the number of treatment days and a 25.9 percent fall in costs per day. Children
      whose primary diagnosis was hyperactivity experienced the largest decrease in
      inpatient costs per treated patient, those diagnosed with schizophrenia
      experienced the smallest decrease, and those diagnosed with substance abuse
      disorders experienced large increases. CONCLUSIONS: Changes in mental health
      service delivery have resulted in substantially reduced access to mental health
      care among children and significant declines in service use and costs among those
      who do receive services.

PMID- 11324740
TI  - Ruptured appendicitis among children as an indicator of access to care.
AB  - OBJECTIVE: To determine factors associated with ruptured appendicitis among
      children, using administrative databases. Insurance-related differences in the
      risk of ruptured appendix among adults in California have previously been
      described (Braveman, Schaaf, Egerter, et al. 1994). DATA SOURCES/STUDY SETTING:
      State of Maryland Medicaid claims data for children < or = 18 years of age from
      1989 to 1993 and hospital discharge data for children < or = 19 years of age from
      1989 to 1994 were analyzed. STUDY DESIGN: Administrative data analysis pre- and
      post-implementation of a Medicaid managed care program called Maryland Access to
      Care. DATA COLLECTION/EXTRACTION METHODS: Medicaid claims and hospital discharge
      ICD-9-CM codes were used to define hospitalization for ruptured and nonruptured
      appendicitis. Linear regression was used to model trends. Logistic regression was
      used to model the probability of ruptured appendicitis. PRINCIPAL FINDINGS: Among
      the 374 Medicaid inpatient claims for appendicitis, 37 percent were for ruptured
      appendicitis. Among the 5,141 hospital discharges for appendicitis, 30 percent
      were for ruptured appendicitis. Using Medicaid claims data, the probability of
      ruptured appendicitis was inversely related to age (OR = 0.86, 95% CI 0.81-0.91),
      white race (OR = 0.35, 95% CI 0.17-0.71) and preventive care visits (OR = 0.19,
      95% CI 0.05-0.77). Using hospital discharge data, age (OR = 0.91, 95% CI 0.90
      0.93) and female gender (OR = 0.87, 95% CI 0.77-0.99) were significant
      covariates. Insurance-related covariates were not significant in multivariate
      models addressing the probability of ruptured appendicitis. CONCLUSIONS: During a
      period of rapid managed care growth, insurance type was not associated with an
      increased risk of ruptured appendicitis among children in this geographic area.
      Age, female gender, and the number of preventive care visits are inversely
      related to the risk of ruptured appendix among children. The protective effect of
      preventive care visits suggests that a primary care relationship facilitates
      access to care, thus reducing delay in the management of appendicitis.

PMID- 11324741
TI  - Comparison of indicators assessing the quality of drug prescribing for asthma.
AB  - OBJECTIVE: To compare different indicators for assessing the quality of drug
      prescribing and establish their agreement in identifying doctors who may not
      adhere to treatment guidelines. DATA SOURCES/STUDY SETTING: Data from 181 general
      practitioners (GPs) from The Netherlands. The case of asthma is used as an
      example because, in this area, different quality indicators exist whose validity
      is questioned. The study is part of the European Drug Education Project. STUDY
      DESIGN: Spearman rank correlations were assessed among the GPs' scores on self
      report instruments, aggregated prescribing indicators, and individualized
      prescribing indicators. Kappa values were calculated as agreement measures for
      identifying low adherence to the guidelines. DATA COLLECTION: Prescribing data
      from GPs were collected through pharmacies, public health insurance companies, or
      computerized GP databases. Two self-report instruments were mailed to the GPs.
      The GPs first received a questionnaire assessing their competence regarding the
      treatment of asthma patients. Three months later they received a series of 16
      written asthma cases asking for their intended treatment for each case. PRINCIPAL
      FINDINGS: Correlations between scores based on self-report instruments and
      indicators based on actual prescribing data were mostly nonsignificant and varied
      between 0 and 0.21. GPs identified as not adhering to the guidelines by the
      prescribing indicators often had high scores on the self-report instruments.
      Correlations between 0.20 and 0.55 were observed among indicators based on
      aggregated prescribing data and those based on individualized data. The agreement
      for identifying low adherence was small, with kappa values ranging from 0.19 to
      0.30. CONCLUSIONS: Indicators based on self-report instruments seem to
      overestimate guideline adherence. Indicators assessing prescribing quality at an
      aggregated level give clearly different results, as compared to indicators
      evaluating prescribing data on an individual patient level. Caution is needed
      when using such prescribing indicators to identify low adherence to guidelines.
      Further validation studies using a gold standard comparison are needed to define
      the best possible indicator.

PMID- 11324742
TI  - Are urban safety-net hospitals losing low-risk Medicaid maternity patients?
AB  - OBJECTIVE: To examine data on Medicaid and self-pay/charity maternity cases to
      address four questions: (1) Did safety-net hospitals' share of Medicaid patients
      decline while their shares of self-pay/charity-care patients increased from 1991
      to 1994? (2) Did Medicaid patients' propensity to use safety-net hospitals
      decline during 1991-94? (3) Did self-pay/charity patients' propensity to use
      safety-net hospitals increase during 1991-94? (4) Did the change in Medicaid
      patients' use of safety-net hospitals differ for low- and high-risk patients?
      STUDY DESIGN: We use hospital discharge data to estimate logistic regression
      models of hospital choice for low-risk and high-risk Medicaid and self
      pay/charity maternity patients for 25 metropolitan statistical areas (MSAs) in
      five states for the years 1991 and 1994. We define low-risk patients as
      discharges without comorbidities and high-risk patients as discharges with
      comorbidities that may substantially increase hospital costs, length of stay, or
      morbidity. The five states are California, Florida, Massachusetts, New Jersey,
      and New York. The MSAs in the analysis are those with at least one safety-net
      hospital and a population of 500,000 or more. This study also uses data from the
      1990 Census and AHA Annual Survey of Hospitals. The regression analysis estimates
      the change between 1991 and 1994 in the relative odds of a Medicaid or self
      pay/charity patient using a safety-net hospital. We explore whether this change
      in the relative odds is related to the risk status of the patient. PRINCIPAL
      FINDINGS: The findings suggest that competition for Medicaid patients increased
      from 1991 to 1994. Over time, safety-net hospitals lost low-risk maternity
      Medicaid patients while services to high-risk maternity Medicaid patients and
      self-pay/charity maternity patients remained concentrated in safety-net
      hospitals. IMPLICATIONS FOR POLICY: Safety-net hospitals use Medicaid patient
      revenues and public subsidies that are based on Medicaid patient volumes to
      subsidize care for uninsured and underinsured patients. If safety-net hospitals
      continue to lose their low-risk Medicaid patients, their ability to finance care
      for the medically indigent will be impaired. Increased hospital competition may
      improve access to hospital care for low-risk Medicaid patients, but policymakers
      should be cognizant of the potential reduction in access to hospital care for
      uninsured and underinsured patients. Public policymakers should ensure that
      safety-net hospitals have sufficient financial resources to care for these
      patients by subsidizing their care directly.

PMID- 11324743
TI  - Medicaid managed care: using research for policy.

PMID- 11324744
TI  - Case management and quality of life: assessing treatment and outcomes for clients
      with chronic and persistent mental illness.
AB  - OBJECTIVE: To examine the impact of treatment setting and exposure to case
      management services on the quality of life of U. S. veterans with chronic and
      persistent mental illness. DATA SOURCES/STUDY SETTING: Data were collected
      longitudinally on a panel of 895 clients enrolled in 14 pilot programs in
      Department of Veterans Affairs long-term psychiatric hospitals by the Serious
      Mental Illness Treatment Research and Evaluation Center during the period 1991
      96. STUDY DESIGN: Data were collected using two primary survey instruments
      (clinician assessment and client assessment) at baseline, every six months for
      the first two years, and every year thereafter, for a total of four years of
      follow-up. Case management exposure over time and its impact on the client's
      quality of life represent the key variables in the study. Additional controls
      included a variety of sociodemographic, socioeconomic, and psychiatric
      characteristics. DATA COLLECTION/EXTRACTION METHODS: Hierarchical linear modeling
      was used to control for potential selection bias, test for the compositional
      effect of treatment setting, and examine the impact of case management exposure
      over time on the individual client's quality of life. PRINCIPAL FINDINGS:
      Increased exposure to case management results in an improved quality of life
      across several domains, including both objective and subjective dimensions for
      health, general, leisure, and social, and the subjective dimension only for
      housing. CONCLUSIONS: The study findings provide managers, clinicians, and
      policymakers a fuller understanding of how this mode of service delivery-case
      management-affects several domains of quality of life for clients with chronic
      illnesses.

PMID- 11324745
TI  - Impacts of Medicaid managed care on children.
AB  - OBJECTIVE: To assess the impact of switching from a fee-for-service (FFS)
      delivery system to managed care on access to, use of, and satisfaction with
      health care for children. DATA SOURCES/STUDY SETTING: A 1998 survey of Medicaid
      recipients in rural Minnesota. STUDY DESIGN: Using a quasi-experimental
      framework, we compare the experiences of children on Medicaid living in counties
      that had switched to managed care with those of children living in counties
      operating under FFS Medicaid. We address the impact of Medicaid managed care
      (MMC) on access to, use of, and satisfaction with care. DATA COLLECTION METHODS:
      A stratified random sample of children on Medicaid was drawn based on Medicaid
      enrollment files. Telephone interviews were conducted with the child's parent or
      guardian between March and June 1998. An overall response rate of 70 percent was
      achieved, yielding a sample of 1,106 children (814 in MMC and 792 in Medicaid
      FFS). PRINCIPAL FINDINGS: We find very few significant differences in access to,
      use of, or satisfaction with health care services for children under MMC relative
      to FFS. MMC did not change the patterns of health care service use or the
      location at which care is delivered, two major goals of MMC initiatives.
      CONCLUSIONS: Our results suggest that the Medicaid program's shift from FFS to
      managed care had little impact on the pattern of children's health care use, the
      location at which they obtained care, or the satisfaction with the care they
      received.

PMID- 11324746
TI  - Outcome trajectories for assisted living and nursing facility residents in
      Oregon.
AB  - OBJECTIVE: To compare assisted living residents and nursing home residents on
      outcome trajectories for three outcomes: ability to perform activities of daily
      living (ADLs), psychological well-being, and pain and discomfort. DATA
      SOURCES/STUDY SETTING: A representative sample of one-third of the census from 38
      participating assisted living facilities (N = 605) and two-fifths of the census
      from 31 participating nursing facilities (N = 610). STUDY DESIGN: A longitudinal
      design using hierarchical linear models to examine how setting (being in an
      assisted living setting or in a nursing home) affected growth trajectories for
      each outcome studied when adjusting for other resident characteristics. DATA
      COLLECTION: Residents or their proxies were interviewed and chart reviews done at
      baseline, six months, and one year. All baseline data were collected between
      August 1995 and May 1996. PRINCIPAL FINDINGS: We found differences in case mix
      between assisted living and nursing facility residents but no differences in
      outcome trajectories for ADLs, psychological well-being, and pain and discomfort.
      For ADLs and pain and discomfort on average, residents in both settings
      experienced change over the study period. For psychological well-being, residents
      experienced no change on average. CONCLUSIONS: The lack of difference in growth
      trajectories for ADLs, pain and discomfort, and psychological well-being between
      the two settings was noteworthy.

PMID- 11324747
TI  - Setting a research agenda for medical errors and patient safety.

PMID- 11324748
TI  - Bacteriophage lambda cIII gene product has an additional function apart from
      inhibition of cII degradation.
AB  - For lysogenization of Escherichia coli cells by bacteriophage lambda, functions
      of three lambda genes called c are necessary. The cI gene codes for a repressor
      that blocks activities of lytic promoters. However, early after infection,
      expression of cI is dependent on the function of the cII gene, coding for a
      specific transcriptional activator. The cII protein is unstable in E. coli cells
      due to FtsH-mediated proteolysis. The cIII gene product is an inhibitor of the
      FtsH protease. Here we demonstrate that cIII may have another function apart from
      inhibition of cII degradation. We found that overexpression of the cII gene
      results in impaired lysogenization by phage lambda, however simultaneous
      overexpression of the cIII gene abolished this negative effect on lysogenization.
      Analysis of cII-mediated transcriptional activation of certain promoters at
      different levels of cII and cIII proteins in cells confirmed that observed
      effects cannot be explained assuming that the only role of cIII is inhibition of
      FtsH-mediated degradation of cII. We propose that cIII has an additional role
      apart from its well-known function in indirect stabilization of cII. Apparently,
      cIII influences not only cII level but also activity of this transcriptional
      stimulator, especially at its high concentrations.

PMID- 11324749
TI  - Comparative analysis of G1 glycoprotein-coding sequences of Cache Valley virus
      (Bunyaviridae: Bunyavirus) isolates.
AB  - The complete 4463 nucleotide sequence for the medium segment viral RNA of Cache
      Valley virus has been cloned and sequenced in four isolates; in addition, the G1
      glycoprotein extracellular coding domains are completed for nine additional
      isolates, including two subtypes, Ft. Sherman (86MSP18) and Tlacotalpan (61D240)
      viruses. The 13 represent isolations spanning over 45 years and a large
      geographic area, including the U.S., Mexico, Canada, and Panama. Glycosylation
      sites in G1 are generally conserved among all except the Ft. Davis, Panama
      (90P686) isolate, which loses a site otherwise conserved within the serogroup.
      Comparison of the G1 coding regions indicates a number of shared amino acid
      substitutions within a centrally located 70 amino acid hypervariable domain,
      which seems to fall outside the primary antigenic domains of G1, most of which
      are found within the amino half of the protein, while a less antigenic region is
      predicted for the carboxyl half of the protein encoded beyond the hypervariable
      domain. Numerous amino acid substitutions are found within various antigenic
      regions, which may be an indication of altered neutralization or hemagglutination
      sites. Putative phosphorylation sites are indicated, most of which are well
      conserved, with the exception of the absence of a specific protein kinase C site
      for the prototype (6V633) virus isolated in Utah. The overall nucleotide identity
      between isolates ranges from 91% (Ft. Sherman subtype, 86MSP18) to 99.4% (North
      Dakota, 1508-A52) as compared to the prototype virus (Utah, 6V633).

PMID- 11324750
TI  - Genomic comparison of an avirulent strain of Orf virus with that of a virulent
      wild type isolate reveals that the Orf virus G2L gene is non-essential for
      replication.
AB  - The genomic structure of two strains of orf virus (OV), a field isolate (MRI
      Scab) which has never been passaged in cell culture, and a multiple-passage cell
      culture-adapted strain (Orf-11) were compared. The Orf-11 genome is approximately
      8.0 kb longer than that of the MRI-Scab due to a duplication of the right-hand
      end. The duplicated region has been translocated to the left-hand end of the
      genome with a loss of sequence from that end. The lost sequence contains three
      complete genes, namely E2L, E3L and G1L and 80% of a fourth gene, namely G2L. The
      sequence lost from G2L in Orf-11 has been replaced by a region of unrelated
      sequence, encoding 98 amino acids. Northern analysis shows that mRNA is expressed
      from this "new" gene. The two viruses were also compared for in vivo virulence
      and ability to protect against subsequent OV challenge. In vivo, the field
      isolate was fully virulent and conferred good protection against challenge,
      whereas the cell culture-adapted virus produced only mild lesions and reduced
      protection against challenge.

PMID- 11324751
TI  - Multiple copies of the upstream regulatory region of the major capsid protein
      gene of bacteriophage MB78 inhibit phage morphogenesis.
AB  - The 2.311 kb EcoRI F fragment of bacteriophage MB78 has been cloned in multicopy
      vectors pUC19 and pCR90. Salmonella typhimurium strains carrying such plasmids
      cannot support development of phage MB78 while other Salmonella phages like P22
      and 9NA grow normally. Most of the phage MB78 induced functions are normal in
      such transformed hosts but proper maturation of the phage particles does not take
      place. Deletion of 138 bp from the 3' end of the cloned fragment reverses the
      inhibitory effect. Analysis of nucleotide and the deduced amino acid sequence of
      a 1.2 kb HindIII-SalI fragment of the phage genome which overlaps the 138 bp
      confirms that this part contains the upstream regulatory region of the major
      structural protein gene. It seems that in presence of multiple copies of the
      upstream regulatory region (which includes a number of promoter like sequence) of
      the coat protein gene, the maturase gene is down regulated and this is effective
      only in cis, a situation quite similar to that of Qbeta RNA phages.

PMID- 11324752
TI  - The product of ORF III in cauliflower mosaic virus interacts with the viral coat
      protein through its C-terminal proline rich domain.
AB  - Using the yeast two-hybrid system, we show that the ORF III product of
      cauliflower mosaic virus (pIII) interacts through its C-terminus with the viral
      coat protein. The last five amino acids of pIII were essential for the
      interaction and virus infectivity. Deletion of the last three amino acids or the
      mutation F129A decreased the strength of the interaction by 90%. We further show
      that pIII is closely associated with virus particles found in the inclusion
      bodies of infected plants but not in viral particles released from the inclusion
      bodies by urea treatment.

PMID- 11324753
TI  - Molecular cloning and high-level expression of G2 protein of hantaan (HTN) virus
      76-118 strain in the yeast Pichia pastoris KM71.
AB  - Hantaan viral G2 envelope gene, which is known to be one of major antigens and
      induce neutralizing antibodies, was cloned into expression vector pHIL-S1 which
      consists of AOX1 promoter, PHO1 signal sequence, HIS4 gene and other components.
      The recombined plasmid was transformed into methylotropic yeast, Pichia pastoris
      of KM71 and recombinant strains harboring multi-copy of G2 gene were selected.
      Expression of the cloned G2 gene was confirmed with Western blot analysis using
      anti-sera of guinea pig immunized with the carboxyl terminal region of G2 protein
      expressed in Escherichia coli. The expression of G2 gene from the recombinant
      strain was tightly repressed by dextrose and effectively induced by methanol, an
      inducer of AOX1 promoter. The highest expression level was observed from 1 day
      after induction and maintained at the same level for up to 4 days.

PMID- 11324754
TI  - Four new inverted terminal repeat sequences from bovine adenoviruses reveal
      striking differences in the length and content of the ITRs.
AB  - The inverted terminal repeat (ITR) of the genome of four bovine adenovirus (BAdV)
      types have been sequenced, analysed and compared to the ITRs of other
      adenoviruses. The length of ITRs of the examined BAdVs ranged between 59 and 368
      base pairs, thus the presently known longest adenovirus ITR sequence is from BAdV
      10. The conserved motifs and characteristic sequence elements of the ITRs
      providing different binding sites for replicative proteins of viral and cellular
      origin seemed to be distributed according to the proposed genus classification of
      BAdVs. The ITRs of BAdV-10 share similarity with the members of the genus
      Mastadenovirus, while the ITRs of the other three sequenced serotypes (BAdV-4, 5
      and strain Rus) which are candidate members of the genus Atadenovirus are very
      short and contain NFI and Sp1 binding sites only. The analysis of the new ITRs
      implied that the nucleotide sequence of the so-called core origin is highly
      preserved within the mastadenovirus genus only.

PMID- 11324755
TI  - Genetic variability of HIV-1 protease from Nigeria and correlation with protease
      inhibitors drug resistance.
AB  - In Nigeria, the most populous country in Africa, the characterization of HIV-1
      strains has been limited. In this study we evaluated the genetic diversity of the
      protease coding region, one of the anti-retroviral therapy target, and
      investigated the presence of mutations related to resistance to HIV protease
      inhibitors. We analyzed samples collected during 1996 and all patients were anti
      retroviral drug naives. Ten samples were evaluated by sequencing of the protease
      gene. The majority, 80%, were classified as subtype A and the two others were
      unclassified-divergent strains, something in between A and G subtypes. The gag
      region from these outliners were sequenced and the phylogenetic analysis
      classified them as subtype G. The protease amino acid consensus sequence of the
      Nigerian subtype A are in complete agreement with the consensus A differing from
      the USA subtype B consensus in 10 positions (L10V, I13V, K14R, I15V, K20I, M36I,
      R41K, P63L, H69K and L89M). The secondary substitutions associated with protease
      inhibitor resistance were observed in all Nigerian sequences at the positions
      L10V, M36I and L89M. The majority of sequence variation was concentrated in the
      interval between aminoacids 70-90 where the protease substrate binding region is
      located.

PMID- 11324756
TI  - Large envelope glycoprotein and nucleocapsid protein of equine arteritis virus
      (EAV) induce an immune response in Balb/c mice by DNA vaccination; strategy for
      developing a DNA-vaccine against EAV-infection.
AB  - Equine arteritis virus (EAV) is a member of the Arteriviridae family, that
      includes lactate dehydrogenase-elevating virus (LDV), porcine reproductive and
      respiratory syndrome virus (PRRSV), and simian haemorrhagic fever virus (SHFV).
      Equine arteritis is a contagious disease of horses and is spread via respiratory
      or reproductive tract. The objective of the present study is to evaluate the
      possibility for developing a model system for prevention horses against an EAV
      infection by DNAvaccination. A cDNA bank from the RNA of EAV was established.
      This gene library contains the translation unit of the EAV open reading frames
      (ORF) 1 to 7. The identity of the cDNA was confirmed by nucleotide sequence
      analysis. Using this defined EAV cDNA gene library the cDNA sequence of the viral
      ORFs were molecularly cloned into the corresponding sites of well characterized
      and powerful expression vectors (pCR3.1, pDisplay, and/or pcDNA3.1/HisC). The
      capability of these recombinant plasmids expressing the gene products of the
      individual viral ORFs 3 to 5, and 7 in induction of an immune response in mouse
      system was investigated. The Balb/c mice (ten mice per assay) were inoculated
      with the DNA of the constructed expression vectors harboring and expressing the
      EAV cDNA of the viral ORFs. The Balb/c mice were injected with about 100 microg
      DNA diluted in 100 microl PBS. The DNA was injected subcutaneously and into the
      tibialis cranialis muscle (Musculus gastrocnemius). The mice were boosted 3 to 5
      times with the same quantities of DNA and under the same conditions at about two
      week intervals. Control mice received the same amount of parental expression
      vectors via an identical route and frequency. The pre- and post-vaccinated sera
      of the individual animals were screened by neutralization tests (NT).
      Neutralizing antibodies against EAV were detected when the animals were
      inoculated with the DNA of the expression vectors harboring cDNA of the EAV ORFs
      5 and 7. Highest NT-titers were observed when the animals were administered with
      the cDNA of ORF 5 and/or with the cDNA of the neutralization determinants of EAV
      that is located on the N-terminal ectodomain of the gene product of ORF 5 between
      the amino acid positions 1-121. These results obtained from these studies
      justified proofing the capability of the EAV cDNA sequences of the viral genes
      including ORFs 5 and 7 in the autologous animal system horse.

PMID- 11324757
TI  - Identification and phylogeny of a protein kinase gene of white spot syndrome
      virus.
AB  - White spot syndrome virus (WSSV) is a virus infecting shrimp and other
      crustaceans, which is unclassified taxonomically. A 2193 bp long open reading
      frame, encoding a putative protein kinase (PK), was found on a 8.4 kb EcoRI
      fragment of WSSV proximal to the gene for the major envelope protein (VP28). The
      identified PK shows a high degree of homology to other viral and eukaryotic PK
      genes. Homology in the catalytic domains suggests that this PK is a
      serine/threonine protein kinase. All of the conserved PK domains are present in
      the WSSV PK gene product and this allowed the alignment with PK proteins from
      other large DNA viruses, which encode one or more PK proteins. An unrooted
      parsonimous phylogenetic tree was constructed and indicated that the PK gene is
      well conserved in all DNA virus families and hence can be used as a phylogenetic
      marker. Baculoviruses to date contain only a single PK gene, which is present in
      a separate well bootstrap-supported branch in the tree. The WSSV PK is not
      present in the baculovirus clade and therefore is clearly separated
      phylogenetically from the baculovirus PK genes. Furthermore, the WSSV PK gene
      does not share a most recent common ancestor with any known PK gene from other
      viruses. This provides further and independent evidence for the unique position
      of WSSV in a newly proposed genus named Whispovirus.

PMID- 11324758
TI  - Comparison of the 5' leader sequences of North American isolates of reference and
      field strains of porcine reproductive and respiratory syndrome virus (PRRSV).
AB  - The 5' leader is documented to be an important regulatory element in many (+)
      ssRNAvirus genome. To understand the significance of the 5' leader RNA of PRRSV,
      we determined the complete leader sequences of fifteen different North American
      strains of PRRSV and predicted their secondary structures. Viruses analysed
      included three reference strains and nine field strains originating from
      different geographic locations. To further examine the leader region, one of the
      field strains was adapted to grow in tissue culture, and three clones were
      isolated. We also predicted the secondary structures of two European strains
      based on their published sequences. The predicted RNA secondary structures of the
      leader sequences suggested the existence of three conserved domains formed by the
      5' region of the leader among the North American strains, two of which were
      conserved in the European strains. A variable structural domain was predicted
      from the 3' region of the leader sequences of the North American strains, where
      all tissue culture-adapted isolates were characterized by a stem-loop while field
      isolates were characterized by an internal bulge within the stem-loop.

PMID- 11324759
TI  - The herpesvirus alkaline exonuclease belongs to the restriction endonuclease PD
      (D/E)XK superfamily: insight from molecular modeling and phylogenetic analysis.
AB  - The PD-(D/E)XK superfamily of deoxyribonucleases (ENases) comprises restriction
      endonucleases, exonucleases and nicking enzymes, which share a common fold and
      the architecture of the active site. Their extreme divergence generally hampers
      identification of novel members based solely on sequence comparisons. Here we
      report a remote similarity between the phage lambda exonuclease (lambda-exo),
      branching out early in the evolutionary history of ENases (3), with the family of
      alkaline exonucleases (AE) encoded by various viruses infecting higher Eukaryota.
      The predicted structural compatibility and the conservation of the functionally
      important residues between AE and ENases strongly suggest a distant evolutionary
      relationship between these proteins. According to the results of extensive
      sequence database mining, sequence/structure threading and molecular modeling it
      is plausible that the AE proteins with lambda-exo and some other putative phage
      encoded exonucleases form a distinct subfamily of PD-(D/E)XK ENases. The
      phylogenetic history of this subfamily is inferred using sequence alignment and
      distance matrix methods.

PMID- 11324760
TI  - Simultaneous analysis of the bidirectional African cassava mosaic virus promoter
      activity using two different luciferase genes.
AB  - The expression of geminivirus genes is controlled by bidirectional promoters
      which are located in the large intergenic region of the circular DNA genomes and
      specifically regulated by virus encoded proteins. In order to study the
      simultaneous regulation of both orientations of the DNA A and DNA B promoters of
      African cassava mosaic virus (ACMV), they were cloned between two different
      luciferase genes with the firefly luciferase gene in complementary-sense and the
      Renilla luciferase gene in virion-sense orientation. The regulation of the ACMV
      promoters by proteins encoded by the complete DNA A, as well as by the
      individually expressed transactivator (TrAP) or replication-associated (Rep)
      proteins was assessed in tobacco and cassava protoplasts using dual luciferase
      assays. In addition, the regulation of the DNA A promoter integrated into tobacco
      genome was also assessed. The results show that TrAP activates virion-sense
      expression strongly both in cassava and tobacco protoplasts, but not in
      transgenic tobacco plants. In contrast to this, DNA A encoded proteins activate
      virion-sense expression both in protoplasts and in transgenic plants. At the same
      time they reduce the expression of the complementary-sense Rep gene on DNA A but
      activate the expression of the complementary-sense movement protein (MPB) gene on
      DNA B. The degree of MBP activation is higher in cassava than in tobacco
      protoplasts, indicating that the plant host also influences the promoter
      strength. Transient transformation experiments using linearized DNA indicate that
      the different regulation of the ACMV DNA A promoter in protoplasts and transgenic
      plants could be due to different DNA curvature in free plasmids and in genes
      integrated in plant genomic DNA.

PMID- 11324761
TI  - High-dose interleukin-2 is an intensive treatment regardless of the  venue of
      administration.

PMID- 11324762
TI  - Controversies in the management of patients with brain metastases.

PMID- 11324763
TI  - The epidermal growth factor receptor-STAT pathway in esophageal cancer.

PMID- 11324764
TI  - Treatment of metastatic renal cell carcinoma with high-dose bolus interleukin-2
      in a non-intensive care unit: an analysis of 124 consecutively treated patients.
AB  - PURPOSE: In prior studies of high-dose interleukin-2 (IL-2) therapy in the
      treatment of metastatic renal cell carcinoma, the majority of patients were
      asymptomatic (65% of patients had Eastern Cooperative Oncology Group [ECOG]
      scores of 0 [no cancer-related symptoms]). These studies demonstrated that an
      ECOG score of 0 predicted an objective antitumor response to IL-2 (P = 0.03). The
      current study determined the response frequency to high-dose IL-2 therapy in a
      primarily symptomatic patient population (ECOG = 1 [presence of cancer-related
      symptoms] for 57.3% of patients). The IL-2 therapy was administered in a non
      intensive care unit (non-ICU). PATIENTS AND METHODS: In this single-institution
      study of high-dose IL-2 therapy, 124 patients were consecutively enrolled and
      treated with the drug. Antitumor responses and safety were assessed by
      radiographic methods and the occurrence of grade 3 and 4 adverse events,
      respectively. RESULTS: The frequency of objective responses was 14.5% (18 of 124
      patients). Seven patients (5.6%) and 11 patients (8.9%) experienced complete
      responses (CRs) and partial responses (PRs), respectively. Two of 7 patients
      (28.6%) with CR and 7 of 11 patients (63.6%) with PR had ECOG scores of 1. The
      median response duration is 18 months for all responders (CR plus PR). The median
      survival duration is 15 months for all patients. It was not possible to estimate
      the median survival duration for all responders because the majority of
      responding patients were alive at close of study. All patients with CR and 5
      patients with PR were alive at close of study. The frequency of grade 3 and 4
      adverse events was comparable to or less than published data and IL-2 was safely
      administered in a non-intensive care unit. CONCLUSION: The frequency of objective
      antitumor responses in patients with ECOG scores of 1 suggests that high-dose IL
      2 therapy may have comparable effectiveness in symptomatic and asymptomatic
      patients. High-dose IL-2 can be administered in a non-ICU setting with acceptable
      toxicity and the chance of clinical benefit.

PMID- 11324765
TI  - Radiosurgery for brain metastases from primary lung carcinoma.
AB  - PURPOSE: Brain metastases are a common problem in patients with lung cancer. This
      retrospective review was performed to describe the efficacy and toxicity of
      stereotactic radiosurgery for brain metastases from lung carcinoma and to
      evaluate prognostic factors for survival. PATIENTS AND METHODS: A retrospective
      review was performed of 113 patients with the diagnosis of lung carcinoma who
      underwent radiosurgery with or without whole-brain radiotherapy for management of
      newly diagnosed or recurrent, single, or multiple brain metastases from 1991
      through 1998 at the University of California, San Francisco. Freedom from
      progression and survival were measured from the date of radiosurgery and
      estimated using the Kaplan-Meier method. Prognostic factors were evaluated with
      the log-rank test and Cox proportional hazards models. RESULTS: The median
      patient age at the time of radiosurgery was 59 years (range, 37-82 years), and
      the median Karnofsky performance score was 90 (range, 50-100). The median
      survival time from radiosurgery was 12.0 months overall, 13.9 months for 41
      patients treated with radiosurgery alone initially, 14.5 months for 19 patients
      treated with radiosurgery and whole-brain radiotherapy initially, and 10.0 months
      for 53 patients with recurrent brain metastases. Among newly diagnosed patients,
      multivariate analysis showed that improved survival was associated with absence
      of extracranial metastases and fewer brain metastases. Among patients with
      recurrent brain metastases, improved survival was associated with higher
      Karnofsky performance score, control of the primary tumor, and fewer metastases.
      Measured by lesion, 1-year local freedom from progression probabilities were 81%
      for radiosurgery alone, 86% for radiosurgery and whole-brain radiotherapy, and
      65% for radiosurgery performed after recurrence. In patients with newly diagnosed
      brain metastases, there was a significantly greater risk of developing subsequent
      brain metastases and of worse overall brain freedom from progression after
      radiosurgery alone versus radiosurgery and whole-brain radiotherapy. One-year
      brain freedom from progression probabilities were 13% without salvage therapy and
      62% with salvage therapy in the 41 patients treated initially with radiosurgery
      alone, versus 67% without salvage therapy and 89% with salvage therapy in the 19
      patients treated initially with radiosurgery plus whole-brain radiotherapy.
      DISCUSSION: Radiosurgery is an effective therapy for selected patients with newly
      diagnosed or recurrent brain metastases from lung carcinoma. Initial whole-brain
      radiotherapy with radiosurgery appears to improve brain control but not survival.
      Prospective, randomized trials are needed to further investigate the role of
      radiosurgery with and without whole-brain radiotherapy for brain metastases.

PMID- 11324766
TI  - Progression of esophageal carcinoma by loss of EGF-STAT1 pathway.
AB  - PURPOSE: In only a very limited number of cultured cell lines, epidermal growth
      factor (EGF), a potent mitogen for many kinds of cells, was shown to activate
      STAT1 (signal transducer and activator of transcription 1) protein, which can
      transmit signals that cause cell growth arrest and apoptosis. The purpose of this
      work is to elucidate the physiologic and/or pathological significance of this EGF
      STAT1 pathway. MATERIALS AND METHODS: A series of cultured cell lines that had
      been established from surgical specimens of esophageal squamous cell carcinoma
      was studied for the existence of the EGF-STAT1 pathway. Normal esophageal
      squamous epithelial cells either explanted from non-neoplastic portions of
      surgically removed human esophageal tissue or in bovine esophageal epithelium in
      situ were examined as well. RESULTS: EGF treatment leads to a strong growth
      arrest in three of the 30 esophageal squamous cell carcinoma cell lines. STAT1
      was found to be activated by EGF in the three cell lines but not in the others.
      EGF can also activate STAT1 in cultured normal esophageal squamous epithelial
      cells. STAT1 is at the activated state in the basal cell layer of the bovine
      esophageal epithelium. Notably, patients who had harbored the cancer cells with
      the EGF-STAT1 pathway had a dramatically better prognosis. DISCUSSION: The EGF
      STAT1 pathway may be intrinsic to esophageal epithelial lineage of cells and is
      lost in a considerable fraction of the carcinomas. This loss appears to cause a
      significantly more malignant clinical course. These findings may point out a
      critical step in the progression of esophageal cancer and could lead to the
      development of useful clinical applications.

PMID- 11324767
TI  - Induction chemotherapy followed by concomitant chemoradiotherapy in the treatment
      of locoregionally advanced oropharyngeal cancer.
AB  - PURPOSE: Locoregionally advanced oropharyngeal cancer has been conventionally
      treated with either surgery and adjuvant radiotherapy or radiotherapy alone, and
      clinical and functional outcomes have been poor. Chemoradiotherapy has been
      demonstrated to improve functional outcome and disease control over conventional
      treatment in recent randomized head and neck trials. Herein, we report overall
      survival, progression-free survival, and patterns of failure in locoregionally
      advanced oropharyngeal cancer treated with induction chemotherapy with or without
      conservative surgery followed by concomitant chemoradiation. MATERIALS AND
      METHODS: Three cycles of induction chemotherapy consisting of cisplatin, 5
      fluorouracil, leucovorin, and interferon alpha-2b (PFL-IFN) were followed by
      conservative, organ-sparing surgery for residual disease. All patients then
      proceeded to concomitant chemoradiation consisting of seven or eight cycles of 5
      fluorouracil, hydroxyurea, and a total radiotherapy dose of roughly 7,000 cGy.
      RESULTS: Sixty-one patients with predominantly stage IV disease were treated.
      Clinical complete response was observed in 65% of patients after induction
      therapy. The median follow-up was 68.0 months for survivors and 39.0 months for
      all patients. At 5 years, overall survival is 51%, progression-free survival is
      64%, locoregional control is 70%, and distant control is 89%. Locoregional
      recurrence accounted for 80% of all initial failures. Only five radical surgeries
      (none were total glossectomy) were performed for initial disease control.
      Treatment-related toxicity accounted for four deaths. CONCLUSION: PFL-IFN given
      with 5-fluorouracil, hydroxyurea, and radiotherapy produces a high rate of cures
      with organ preservation in a disease group that has traditionally fared poorly.
      Local and distant disease control and survival rates exceed those observed with
      more standard treatment approaches involving surgery and radiotherapy. Further
      investigation into chemoradiotherapy as a curative modality for this disease is
      warranted.

PMID- 11324768
TI  - Cancer patients use unconventional medical therapies far more frequently than
      standard history and physical examination suggest.
AB  - BACKGROUND: Studies with questionnaires have suggested that many cancer patients
      utilize unconventional medical therapies (UMT). There are few data evaluating
      directed questions about the use of UMT. This study was performed to determine if
      careful directed questioning about UMT reveals a higher rate of utilization
      compared to standard history and physical examination. MATERIALS AND METHODS: A
      prospective evaluation of 196 consecutive patients presenting for initial
      consultation at the University of Pennsylvania was performed. Each patient
      underwent standard history and physical examination, including questions
      regarding prescription and over-the-counter medications. At the completion of
      standard questioning, patients were asked an explicit set of directed questions
      regarding the utilization of UMT. The median age of the patient population was 61
      years (range = 28-80 years). Cancer diagnoses included breast (19%), lung (28%),
      prostate (26%), and other (27%). Females constituted 32% of the patient
      population. RESULTS: Initially, only 13 patients (7%) revealed they were using
      UMT during a standard history and physical. Evaluation of the remaining 183
      patients with directed questioning revealed an additional 66 patients (36%) were
      utilizing these therapies. Of the 79 patients taking UMT, 84% were identified by
      directed questioning and 16% by standard history and physical examination (P <
      0.0005). Forty-one patients (52%) were using > or = 2 of these therapies (mean =
      2.5; range 1-17 therapies). A total of 48 different UMT were used by this patient
      population. Patients utilizing multivitamin supplementation were significantly
      more likely to be using an UMT than those who were not (68% vs. 31%; P < 0.0001).
      Females were more likely to use UMT than males (49% vs. 35%; P = 0.08).
      CONCLUSIONS: The addition of explicitly directed questioning to the standard
      history and physical examination significantly increases the oncologist's ability
      to identify cancer patients who utilize UMT. Some of these therapies may interact
      with conventional cancer treatments and/or cause significant side effects;
      consequently, it is important for oncologists to detect those patients utilizing
      these therapies.

PMID- 11324769
TI  - Outpatient taxol and carboplatin chemotherapy for suboptimally debulked
      epithelial carcinoma of the ovary results in improved quality of life: an Eastern
      Cooperative Oncology Group Phase II Study (E2E93).
AB  - PURPOSE: The combination of a platinum compound and paclitaxel is a standard
      treatment for ovarian cancer. In this cooperative group trial, paclitaxel and
      carboplatin were combined in an outpatient schedule to determine the clinical
      benefit, toxicities, and effect on quality of life. PATIENTS AND METHODS: Women
      with International Federation of Gynecology and Obstetrics stage II to IV
      epithelial ovarian cancer with suboptimal residual disease (> 1 cm) were
      eligible. Paclitaxel, 150 mg/m2, was given over 3 hours, followed by carboplatin
      (area under the curve, 5). This was repeated every 4 weeks for six cycles.
      Quality of life was assessed using the Functional Assessment of Cancer Therapy
      Ovarian Cancer scale. Fifty-nine patients were enrolled, 38 with measurable
      disease and 21 with evaluable disease. RESULTS: The response rate (complete
      response + partial response) was 72%. The progression-free interval for patients
      with measurable disease was 17.5 months and for patients with evaluable disease
      was 11.1 months. Median survivals were 30.1 months (measurable) and 25.7 months
      (evaluable). Toxicities were modest. Quality-of-life scores improved
      significantly during therapy. DISCUSSION: This regimen is ideal for most women
      with advanced ovarian cancer because it is convenient and well tolerated, with
      response and survival comparable to those of more aggressive regimens. Overall
      quality-of-life scores and physical well-being scores improved throughout this
      outpatient treatment regimen for most patients.

PMID- 11324770
TI  - Combined radiation therapy and chemotherapy for carcinoma of the cervix.
AB  - Cervical cancer is the third most common cancer affecting women worldwide.
      Surgery, radiation therapy, and chemotherapy have been used in various settings
      in an effort to improve survival rates of patients with cervical cancer. Recent
      cooperative clinical trials have demonstrated a benefit from the concurrent use
      of chemotherapy and radiation therapy to treat cervical cancer. These studies
      have provided the most significant improvement in the treatment of locally
      advanced disease in more than 30 years. This review summarizes studies of
      sequential and concurrent combinations of chemotherapy and radiation therapy for
      the treatment of cervical cancer, as well as the recent controversies related to
      this treatment.

PMID- 11324771
TI  - Radiofrequency ablation of solid tumors.
AB  - Radiofrequency ablation of solid tumors is produced by frictional heating caused
      when ions in the tissue attempt to follow the changing directions of a high
      frequency alternating current. The radiofrequency probe is typically placed under
      ultrasound guidance, and the ablation is performed with real-time ultrasound
      monitoring. Radiofrequency ablation has been demonstrated to be effective in the
      treatment of unresectable hepatic tumors, and promising results have also been
      obtained in tumors of the lung, bone, brain, kidney, prostate gland, and
      pancreas. Most recently, radiofrequency ablation has been tested in the treatment
      of invasive breast tumors. A preliminary study reported that intraoperative
      radiofrequency ablation causes invasive breast cancer cell death in patients with
      locally advanced breast cancer. An ongoing study is investigating the use of
      radiofrequency ablation for the treatment of breast tumors 2 cm or less in
      diameter.

PMID- 11324772
TI  - Issues in cross-cultural research: an overview.

PMID- 11324773
TI  - Quality of life profiles in the first years of rheumatoid arthritis: results from
      the EURIDISS longitudinal study.
AB  - OBJECTIVE: The aim of this study was to examine the quality of life (QoL)
      profiles of patients with early rheumatoid arthritis (RA) and to relate these to
      disease and impairment variables as indicated, respectively, by erythrocyte
      sedimentation rate (ESR) and by tender joint count (Ritchie Articular Index),
      fatigue, and pain. METHODS: The present study uses part of the European Research
      on Incapacitating Disease and Social Support data of 573 patients with recently
      diagnosed RA (268 from the Netherlands, 216 from Norway, and 89 from France). A
      series of clinical and psychosocial data were collected on 4 (the Netherlands,
      France) and 3 (Norway) occasions, with 1-year intervals separating the waves of
      data collection. RESULTS: Of the disease activity (ESR) and impairment variables
      (tender joint count, fatigue, pain), fatigue was identified as the consequence of
      disease that differentiated best on a series of QoL aspects such as disability,
      psychological well-being, social support, and "overall evaluation of health."
      Next came pain and tender joint count, and ESR showed by far the least
      differentiating ability. A principal-component analysis on the QoL measures used
      in this study yielded one general factor measuring "overall QoL." After rotation,
      two separate factors were encountered, one referring to the physical domain and
      the other to the psychological and social domains of QoL. Again, the QoL of RA
      patients experiencing much fatigue appeared to decline the most. CONCLUSIONS:
      Because of the highly variable nature of RA, impairments, activities of daily
      living (ADL) and instrumental ADL restrictions, and psychosocial distress can
      vary erratically. In particular, "fatigue" as measured over a period of 2 to 3
      years distinguished best among RA patients as shown by their QoL profiles.
      Although the physical domain was most affected, the significant effect of RA on
      the psychosocial domain should not be underestimated.

PMID- 11324774
TI  - Effects of stress management on pain behavior in rheumatoid arthritis.
AB  - OBJECTIVE: To examine the effects of stress management training on pain behavior
      exhibited by persons with rheumatoid arthritis (RA) and the relationship of
      change in pain behavior with certain patient characteristics as well as change in
      self-reported levels of pain. METHODS: Patients with RA (n = 131) were randomly
      assigned to 1 of 3 groups: a stress management group, an attention control group,
      or a standard care control group. The stress management and attention control
      groups received a 10-week intervention followed by a 15-month maintenance phase.
      RESULTS: The 3 groups did not differ significantly in the change in pain behavior
      at any of the assessment periods. However, persons with RA who had less disease
      activity tended to exhibit positive changes in pain behavior over time. Changes
      in self-reported pain were not significantly related to changes in pain behavior.
      CONCLUSION: The results indicate that stress management interventions do not
      reduce total pain behaviors exhibited by persons with RA. Changes in pain
      behaviors appear to be related to disease activity, age, and disease duration,
      but not to changes in self-reported measures of pain.

PMID- 11324775
TI  - Cardiac manifestations of rheumatoid arthritis: a case-control transesophageal
      echocardiography study in 30 patients.
AB  - OBJECTIVES: Current knowledge of the cardiac manifestations of rheumatoid
      arthritis (RA) stems only from clinical and transthoracic echocardiography (TTE)
      studies. To determine the incidence and type of heart lesions in RA, we coupled
      TTE with transesophageal echocardiography (TEE), which is more sensitive and more
      accurate. METHODS: Thirty unselected RA patients (26 women and 4 men aged 27 to
      84 years, with a mean age of 57.8+/-15.1 years) free of known progressive heart
      disease underwent a chest radiograph, an electrocardiogram, laboratory tests, and
      TTE coupled with TEE. Results were compared with those in age- and sex-matched
      patients who were free of rheumatic disease and who underwent TEE to investigate
      a neurologic or cardiologic disorder. RESULTS: Mitral regurgitation (MR) was
      evidenced in 24 cases (80%). Among the controls, only 11 (37%) had MR (P <
      0.001). Aortic regurgitation was found in 10 cases (33%), versus 7 controls (not
      significant-NS). Seven cases (23%) versus only 2 controls (7%) had tricuspid
      valve abnormalities (NS). Pericarditis was found in 4 cases (13%) and in none of
      the controls. Eleven cases had evidence of cardiomyopathy (37%) and 12 (40%) had
      atheroma of the aorta, this last being missed by TTE in 10 patients. Echo
      generating nodules were seen on a mitral valve in 2 cases and on an aortic valve
      in 1. We found no correlations linking cardiac lesions to clinical or laboratory
      features of RA. CONCLUSION: Our study demonstrated that cardiac involvement,
      particularly of the mitral valve, is extremely common in RA patients.

PMID- 11324776
TI  - Preference for disclosure of information among patients with rheumatoid
      arthritis.
AB  - OBJECTIVE: To quantify preference for disclosure of information among patients
      with rheumatoid arthritis (RA) and to examine sex-specific correlates of
      information preference. METHODS: We interviewed patients with RA and assessed
      preference for disclosure of information using 4 questions from the previously
      validated "Information Preference Seeking Scale." Three questions addressed
      preference for disclosure of side effects and 1 question addressed preference for
      disclosure of therapeutic options. Associations between preference for
      information and patient characteristics were examined using stepwise multiple
      linear regression. RESULTS: One hundred RA patients (mean age 68+/-12 years; 73%
      female) were interviewed; 89 respondents agreed or strongly agreed with all 4
      statements reflecting a preference for full disclosure, and an additional 8
      respondents agreed or strongly agreed with 3 of the 4 statements. The mean score
      (+/- SD) for information preference was 86+/-13, on a scale from 0 to 100 where
      100 reflected a strong preference for full disclosure. In bivariate analyses,
      female sex and current employment were associated with stronger preferences for
      being informed (mean score for women 88+/-11, for men 80+/-15 [P = 0.02]; for
      employed 92+/-11, for unemployed 84+/-13 [P = 0.04]). Multivariate sex-specific
      analyses demonstrated that current employment and higher education level were
      positively associated with preference for disclosure among women and men,
      respectively. CONCLUSION: The results of our survey suggest that RA patients want
      to be fully informed about the risks associated with medications and about
      alternative options. The challenge remaining for rheumatologists is how to
      effectively communicate the risks and benefits related to the many options that
      are currently available for RA patients.

PMID- 11324777
TI  - Giant cell arteritis with low erythrocyte sedimentation rate: frequency of
      occurence in a population-based study.
AB  - OBJECTIVE: To determine the frequency of a low erythrocyte sedimentation rate
      (ESR) in patients with giant cell arteritis (GCA) and evaluate their clinical
      features in a defined population. METHODS: A total of 167 patients with GCA were
      identified in the population of Olmsted County, Minnesota, between the years 1950
      and 1998 using methods described in previous studies. All fulfilled American
      College of Rheumatology criteria for GCA. RESULTS: In 9 of the 167 patients the
      ESR was less than 40 mm/hour (Westergren method) at diagnosis. These patients had
      less frequent systemic symptoms and visual symptoms than the others. No patient
      with low ESR developed blindness. Other manifestations were similar in those with
      low and those with high ESR. The response of symptoms to prednisone treatment was
      within 1 week, and after a median of 25 days of therapy the median ESR dropped
      from 19 mm/hour to 3 mm/hour. The median duration of glucocorticoid therapy in
      the 9 patients was 21.5 months and median followup after diagnosis was 12.5
      years. Over a long period of observation (median 44 years) in the 9 patients with
      low ESR, 9 inflammatory events other than GCA were observed in 7 patients. The
      ESR was normal in 7 of these 9 other events. CONCLUSION: A low ESR in active GCA
      is not a rare occurrence. Causes may include localized arteritis in some patients
      and an inability to mount an acute phase serologic response in others.

PMID- 11324779
TI  - Health-related quality of life of patients with psoriatic arthritis: a comparison
      with patients with rheumatoid arthritis.
AB  - OBJECTIVE: To compare health-related quality of life (QOL) between patients with
      psoriatic arthritis (PsA) and patients with rheumatoid arthritis (RA), using the
      Medical Outcomes Study Short Form health survey (SF-36) and the Health Assessment
      Questionnaire (HAQ). METHODS: Both the SF-36 and the HAQ were administered to 107
      PsA patients attending the University of Toronto Psoriatic Arthritis Clinic
      between January 1 and December 31, 1994, and to 43 RA patients attending a
      University of Toronto-affiliated RA clinic during the same period. Standardized
      assessments of disease activity and severity were also performed at each clinic
      visit. Logistic regression analysis was used to compare health-related QOL
      between PsA and RA. RESULTS: Both patient populations experienced lower physical
      health compared with that of a general population sample. The RA patients
      demonstrated more active inflammatory disease at the time of assessment than the
      PsA patients. The PsA patients were younger, and more were men. Logistic
      regression analyses showed that patients with PsA reported higher levels of
      vitality than patients with RA, even after adjusting for the observed differences
      in clinical and demographic characteristics. PsA patients, however, reported more
      role limitations due to emotional problems and more bodily pain after adjusting
      for the difference in vitality and other covariates. CONCLUSIONS: Although both
      patient populations experienced reduced QOL, there were some meaningful
      differences in how the 2 conditions affect health-related QOL. Further, it
      appeared that there may be unique disabilities associated with the psoriasis
      dimension of PsA.

PMID- 11324778
TI  - Open trial of methotrexate as treatment for autoimmune hearing loss.
AB  - OBJECTIVE: To assess the efficacy of low-dose methotrexate (MTX) administered for
      the treatment of autoimmune hearing loss. METHODS: This was a prospective, 12
      month, open-label study of 17 patients with refractory autoimmune hearing loss.
      All patients had ongoing episodic worsening of hearing in one or both ears prior
      to enrollment despite traditional medical therapy. The MTX dose was 7.5-25
      mg/week. Hearing loss and vertigo were evaluated at baseline and at completion of
      the study. Hearing improvement was defined as an improvement in pure tone
      threshold (PT) average of >10 dB or an increase in speech discrimination (SD) of
      >15%; worsening was defined as a decrease of >10 dB in PT or a decrease of >15%
      in SD in at least one ear. RESULTS: MTX was well tolerated. Among patients with
      Meniere's disease, 5 of 9 had improvement or resolution of vertigo. Equilibrium
      improved in all 3 patients with Cogan's syndrome and improved in 2 out of 3
      patients with idiopathic hearing loss and this symptom. According to the
      parameters defined above, hearing improved in 11 patients (65%), was unchanged in
      4 patients (23%), and worsened in 2 patients (12%). CONCLUSION: Long-term low
      dose MTX therapy may be a useful therapy for at least some patients who have
      hearing loss with a presumptively autoimmune-mediated component that is
      refractory to traditional therapies.

PMID- 11324780
TI  - Development and preliminary validation of a children's arthritis self-efficacy
      scale.
AB  - OBJECTIVE: To develop a valid and reliable measure of arthritis self-efficacy for
      use with school-age children with juvenile idiopathic arthritis (JIA). METHODS:
      Construction of the 11-item Children's Arthritis Self-Efficacy Scale (CASE) was
      based on an existing body of knowledge and the results of focus groups with
      children, their parents, and health professionals. Data for validation of the
      CASE were collected by self-administered questionnaires completed by 89 children
      and 151 caregivers. RESULTS: Analyses revealed a 3-factor structure relating to
      self-efficacy for managing symptoms, emotional consequences, and activities,
      explaining 76.5% of the total variance. The CASE demonstrated high internal
      consistency, concurrent validity, and construct validity. CONCLUSION: Preliminary
      findings suggest that the CASE is worthy of further psychometric testing and may
      have the potential to help delineate variations in adjustment among children with
      JIA.

PMID- 11324781
TI  - An English and Spanish quality of life measure for rheumatoid arthritis.
AB  - OBJECTIVE: To develop a rheumatoid arthritis-specific health-related quality of
      life instrument, translate the English instrument into Spanish, and test the
      scaling assumptions, reliability, validity, and feasibility of both the English
      and Spanish versions. METHODS: The development of the Quality of Life-Rheumatoid
      Arthritis Scale (QOL-RA Scale) involved literature review, consultations with
      experts, 40 face-to-face interviews, and 5 focus group discussions with
      multiethnic and multilingual women with rheumatoid arthritis (RA). Translation
      design facilitated conceptual and linguistic equivalence. Data for the
      psychometrics came from telephone interviews of a sample of 107 Caucasian/English
      and 80 Hispanic/Spanish women with RA. The instruments were (a) the Arthritis
      Impact Measurement Scales 2 (AIMS2), (b) the Lubben Social Network Scale (LSNS),
      (c) the Center for Epidemiologic Studies-Depression Scale (CES-D), and (d) the
      QOL-RA Scale. Descriptive statistics, significance tests, Cronbach's alpha
      technique, correlation, and factor analysis were used. RESULTS: The QOL-RA Scale,
      an 8-item scale, took 2 to 3 minutes to administer. Psychometric analysis
      revealed that the psychometric attributes and constructs of both English and
      Spanish questionnaires are comparable (i.e., equivalent). Both versions
      demonstrated the following: (a) normal distribution of the QOL-RA Scale, roughly
      symmetrical distributions of the items, equivalent means and standard deviations
      across items, and less than 10% floor and ceiling effects, (b) Cronbach's alpha
      coefficients of 0.87-0.90, (c) significant correlations of the QOL-RA Scale with
      the AIMS2 subscales, LSNS, and CES-D, ranging from 0.25 to 0.66 (P < or = 0.01),
      and (d) extraction of 2 factors, namely physio-psychological and socio
      psychological, that explained 65% to 73% of the variance in the scale scores.
      CONCLUSION: The QOL-RA Scale, in both English and Spanish versions, appears to
      meet the assumptions of a summated rating scale and the criteria of relevance,
      reliability, validity, feasibility, and adaptability to several languages.

PMID- 11324782
TI  - Use of the Americans with Disabilities Act by persons with rheumatic diseases and
      factors associated with use.
AB  - OBJECTIVE: This study examined use of the Americans With Disabilities Act (ADA)
      among persons with rheumatic diseases and assessed which factors were associated
      with use. METHODS: A mail survey was conducted among adult patients recruited
      from 21 rheumatology practices. Subjects answered questions about their
      inclination to use the ADA in the community or at work and about factors thought
      to be associated with use. The outcome was stage of behavior change, the behavior
      being use of the ADA. Ordinal logistic regression identified independent
      correlates of the outcome. RESULTS: Of 631 subjects, 47% experienced an ADA
      resolvable barrier to community activity, and 63% of 183 employed subjects needed
      a job accommodation or experienced health discrimination. However, only 7% of the
      full sample and 10% of the employed subgroup had used the ADA. Factors associated
      with use were detailed knowledge, perception of being disabled, skill in
      requesting use, and health professional use suggestion. CONCLUSIONS: Although
      many persons with rheumatic diseases experience community barriers or need
      workplace accommodations, they currently underutilize the ADA. Use could be
      enhanced by health professional suggestion and referral or by community programs
      designed to address the factors identified.

PMID- 11324783
TI  - The onset of generalized osteoarthritis in older women: a qualitative approach.
AB  - OBJECTIVE: This qualitative study aims to investigate which factors are possibly
      associated with the onset of generalized osteoarthritis (OA) in older women.
      METHODS: The study population was recruited from participants of a group course,
      "Coping With Osteoarthritis of the Hip or Knee." Twenty-three women with
      generalized OA were identified, 20 of whom participated in a semistructured
      interview at home. All data were self-reported by the subjects. RESULTS:
      Hereditary factors were present in 17 women. Metabolic factors (such as
      impairments in carbohydrate and lipid metabolism, diabetes, etc.) were not
      prevalent. Twelve women thought that certain diets influenced their pain
      symptoms. Five women spontaneously mentioned their health status during the
      Second World War as a cause of their OA. Four considered too much stress as being
      a cause, and in 13 women symptoms started after a period of stressful life events
      or depression. CONCLUSION: According to the respondents, depression, stress, and
      diets are associated with the onset and worsening of their generalized OA.
      Heredity and a low health status at a vulnerable age may also be important. These
      findings could generate new hypotheses that can be tested in future quantitative
      studies.

PMID- 11324784
TI  - Systemic lupus erythematosus in three ethnic groups. VII [correction of VIII].
      Predictors of early mortality in the LUMINA cohort. LUMINA Study Group.
AB  - OBJECTIVE: To determine the features associated with mortality in a multiethnic
      US cohort of patients with systemic lupus erythematosus (SLE) within 5 years of
      study onset. METHODS: Socioeconomic and demographic features (age, gender,
      ethnicity, marital status, education, occupation, poverty, and health-related
      behaviors [drinking, smoking, exercising]), clinical and immunologic features
      (disease duration, disease onset type, disease activity according to the Systemic
      Lupus Activity Measure [SLAM], disease damage according to the Systemic Lupus
      International Collaborating Clinics [SLICC] Damage Index [SDI], number of
      American College of Rheumatology criteria at diagnosis, organ system
      manifestations, fatigue and pain ratings, and medication usage and
      autoantibodies), immunogenetic features (HLA class II genotypes), and behavioral
      and psychosocial features (social support, illness-related behaviors, and
      helplessness), as obtained at enrollment into the study, were compared between
      survivors and deceased patients. Logistic regression analysis was used to
      determine significant independent risk factors for mortality. RESULTS: Within 5
      years of study onset, 34 of 288 patients have died. Fourteen deaths could be
      directly attributed to SLE and 11 to infections. In 1 patient the cause of death
      could not be determined. In the remaining 8 patients the cause of death was
      neither infectious nor disease-related. There were 10 deaths among Hispanics, 18
      among African Americans, and 6 among Caucasians (P < 0.05). Variables associated
      with mortality in the univariable analyses included poverty, less than full-time
      employment, difficulty in accessing health care, shorter disease duration,
      cardiovascular and renal involvement, higher serum creatinine levels and lower
      hematocrit values, higher SLAM and SDI scores, lower use of antimalarial drugs,
      and higher use of (some) immunosuppressants. Specific autoantibodies and class II
      HLA genotypes were not associated with mortality. Poverty and higher baseline
      SLAM and SDI scores were independently associated with mortality in the
      multivariable analyses. CONCLUSIONS: Disease activity, disease damage, and
      poverty appear to be the most important determinants of mortality in this
      multiethnic US cohort of SLE patients. These results have applicability to the
      management of patients with SLE, a disease that more severely affects
      disadvantaged minority population groups.

PMID- 11324785
TI  - Sociocultural issues in clinical research.

PMID- 11324786
TI  - Adaptation into Danish of the Stanford Health Assessment Questionnaire (HAQ) and
      the Rheumatoid Arthritis Quality of Life Scale (RAQoL).
AB  - OBJECTIVES: The study was designed to adapt the Stanford Health Assessment
      Questionnaire (HAQ) and the Rheumatoid Arthritis Quality of Life Questionnaire
      (RAQoL) for use in Denmark. METHOD: The instruments were translated into Danish
      and then field-tested with 10 RA patients for relevance, and face and content
      validity. Reliability and validity were assessed by administering the new
      measures and a comparator instrument (the Danish Nottingham Health Profile) to 80
      RA patients on two occasions. RESULTS: Patients found both measures acceptable
      and easy to complete. They had good test-retest reliability (>0.90) and internal
      consistency and were both able to discriminate between groups with different
      levels of functional status and self-perceived severity. When compared with the
      NHP sections, both measures showed expected convergence and divergence.
      CONCLUSION: Given the excellent psychometric properties of the Danish versions of
      the RAQoL and HAQ, both are recommended for inclusion in clinical trials and
      studies.

PMID- 11324787
TI  - Up-regulation of CD44 in rheumatoid chondrocytes.
AB  - The adhesion molecule CD44 is thought to play an important role in the
      inflammatory process. To identify the expression of CD44 in articular
      chondrocytes in rheumatoid arthritis (RA), monoclonal anti-CD44 antibodies were
      immunohistochemically used to react with articular cartilage specimens of 15
      patients with RA, 9 with osteoarthritis (OA), and 6 with femoral neck fracture
      (FF). The proportion of CD44-positive chondrocytes in RA was 93 +/- 2% (N=16),
      which was significantly higher than that in OA (59 +/- 7%, N=9, p<0.001) and FF
      (46 +/- 5%, N=6, p<0.001). Among CD44 isoforms examined, the hemopoietic form was
      dominant in chondrocytes in RA. Therefore, up-regulation of CD44 on chondrocytes
      may play a significant role in cartilage degeneration in RA.

PMID- 11324788
TI  - Giant cell arteritis and secondary amyloidosis: the natural history.
AB  - Giant cell (temporal) arteritis (GCA) may be a cause of fever of unknown origin
      (FUO) in elderly patients. The development of secondary (reactive) amyloidosis is
      an unusual complication of the disease. We describe a 65-year-old male patient
      who was hospitalized in our hospital with FUO and was diagnosed as having GCA 5
      years later. At that time, he also had a nephrotic syndrome and secondary
      amyloidosis (AA-type). He died due to end-stage renal failure. The probable
      explanation for the development of this rare complication might be the late
      diagnosis of this chronic inflammatory disease, which was left untreated for a
      long period of time.

PMID- 11324789
TI  - Pseudolymphoma of the liver associated with Sjogren's syndrome.
AB  - Sjogren's syndrome (SS) is known to be associated with pseudolymphoma in several
      organs. We describe a patient with SS complicated by a hepatic pseudolymphoma.
      Although the development of a hepatic pseudolymphoma is extremely rare, this
      disorder should be taken into consideration in the differential diagnosis of
      space occupying lesions related to autoimmune diseases such as SS.

PMID- 11324790
TI  - The coexistence of systemic lupus erythematosus and multiple sclerosis in a
      mother and daughter.
AB  - The occurrence of both multiple sclerosis (MS) and systemic lupus erythematosus
      (SLE) has previously been described in several members within the same family and
      in twins of successive generations, but the finding of both diseases in one
      patient is a great rarity. We here report on a rare coexistence of MS and SLE
      both in mother and daughter. Both patients fulfill the diagnostic criteria of
      primary-progressive subtype of MS as well as SLE. The finding constitutes
      supporting evidence of a common genetic background for these two autoimmune
      disorders.

PMID- 11324791
TI  - Were the patterns of treatment for rheumatoid arthritis during 1977-1992
      consistent with modern clinical guidelines?
AB  - OBJECTIVE: Quality assessment of the long-term treatment of patients with
      rheumatoid arthritis (RA). METHODS: Treatment patterns in a cohort of 70 local
      and 77 distant RA patients during 1977-1992 were reviewed retrospectively and
      compared to modern clinical guidelines. RESULTS: In 1977 disease-modifying anti
      rheumatic drugs (DMARDs) were given to 62% of the new, hospitalised patients,
      systemic corticosteroids to 7%, and corticosteroid joint injections to 24%.
      Patients with short disease duration and/or serious disease were selected for
      DMARD-treatment. Rheumasurgery was performed on 21%. During follow-up of local
      patients 54% were recorded with DMARDs for a mean duration of 29 months;
      approximately 1/5 of the follow-up period. Methotrexate was used infrequently.
      Local and systemic corticosteroids were recorded in approximately 20%.
      Rheumasurgery, predominantly non-prosthetic, was performed on 27%. CONCLUSIONS:
      Patients with early and serious disease were selected for DMARD-therapy, but the
      treatment duration was too short for modern requirements. Pharmaceutical and
      surgical treatment patterns were otherwise mainly consistent with present
      guidelines.

PMID- 11324792
TI  - Lower extremity isometric joint torque in children with juvenile chronic
      arthritis.
AB  - OBJECTIVE: To determine the intratester reliability of joint torque testing with
      a hand-held dynamometer (HHD) during contractions of four major lower extremity
      muscles in children with juvenile chronic arthritis (JCA) and to compare results
      for children with JCA to results for children without disability. METHODS: Eleven
      children with JCA and 14 children with normal musculoskeletal function were
      tested with a HHD using isometric muscle contractions of the right quadriceps,
      hamstrings, tibialis anterior and triceps surae. RESULTS: Intratester reliability
      values exceeded the 0.92 level, regardless of the number of trials, for all
      motions tested. Statistically lower joint torque values were found in a subgroup
      of children with JCA for contractions of the tibialis anterior (p=0.003) and
      triceps surae (p=0.05) muscles. CONCLUSIONS: HHD offers a reliable means of
      testing the joint torque generated with contraction of these lower extremity
      muscles in children with JCA. Findings in children with JCA compared to children
      without disability agree with previous reports concerning quadriceps muscle
      function, but also point to concerns for muscles associated with generating ankle
      joint torque.

PMID- 11324793
TI  - Gastro-intestinal permeability is increased in patients with limited systemic
      sclerosis.
AB  - OBJECTIVE: to evaluate gastro-intestinal (GI) permeability in patients with
      limited systemic sclerosis (LSS) at baseline and after oral acetylsalicylic acid
      (ASA). METHODS: 13 patients with LSS and 10 controls were studied. Baseline GI
      permeability was assessed with orally administered sucrose, mannitol, and
      lactulose. Gastric lesions and Helicobacter status were investigated by
      endoscopy. In 5 patients and 6 controls (with normal baseline permeability) the
      GI permeability response was assessed after oral ASA. RESULTS: compared with
      controls, gastric (p<0.05) and intestinal (p<0.02) permeability was higher in LSS
      patients, at baseline. After oral ASA gastric permeability (sucrose) increased in
      both groups (controls: 186%, LSS: 265%), whereas the lactulose/mannitol ratio
      raised significantly only in LSS (+31% and +148%; p<0.05 vs controls).
      CONCLUSIONS: baseline permeability is altered in LSS; the exaggerated response of
      the small intestine to ASA may represent a genetically determined or a disease
      related dysfunction of the mucosal barrier.

PMID- 11324794
TI  - Connective tissue disease after hip and knee implant surgery.
AB  - OBJECTIVE: To increase the knowledge of the long-term effects of artificial hip
      and knee joint implants. METHODS: The study groups consisted of 24,636 patients
      with osteoarthritis who underwent hip implant surgery and 5,221 who received knee
      implants during 1977-89. The post-implant rate of hospitalization for connective
      tissue disease (CTD) was compared with the rate in the general population of
      Denmark and with that among osteoarthritis patients without implant surgery.
      RESULTS: The rates of hospitalization for CTD were higher than the background
      level among both hip and knee implant patients with osteoarthritis, whereas the
      comparison with non-implanted osteoarthritis patients revealed that the
      hospitalization rate for CTD was reduced after hip implant surgery, but increased
      after knee implant surgery. CONCLUSION: Since the materials used in hip and knee
      implants in Denmark are not substantially different, these results are unlikely
      to reflect an implant effect but rather the selection criteria of referral for
      implant surgery.

PMID- 11324795
TI  - Clinical utility of diagnostic tests for rheumatoid factor.
AB  - OBJECTIVE: To investigate and compare the accuracy and usefulness of diagnostic
      tests for rheumatoid factor (RF). METHODS: In a cross-sectional study sera
      derived from patients admitted to the Section of Rheumatology were tested for
      presence of RF using either nephelometry or the Waaler test. Diagnostic
      sensitivity and predictive values of the tests were calculated and compared. The
      accuracy of the tests was compared using receiver-operating characteristics (ROC)
      methodology. RESULTS: Good agreement was found between the tests (kappa
      approximately 0.7). At cut-off 19 IU/mL nephelometry showed the highest
      sensitivity (82.4%) and specificity (95.9%) for rheumatoid arthritis (RA). In
      comparison, the Waaler test had a sensitivity of 60.3% and specificity of 95.9%
      at cut-off titer 128. The tests showed nearly equal performance characteristics
      when predicting SS. CONCLUSION: Although both tests exhibit good performance
      characteristics, nephelometry has a higher accuracy when predicting RA and SS.
      The common practice of using both tests for detection of RF is not recommended.

PMID- 11324796
TI  - EMG activity and pain development in fibromyalgia patients exposed to mental
      stress of long duration.
AB  - OBJECTIVE: To examine the distribution of stress-induced upper-body pain in
      fibromyalgia patients, and the possible association of pain with
      electromyographic activity in muscles near the sites of pain development.
      METHODS: Fifteen fibromyalgia patients and 15 pain-free subjects were exposed to
      low-level mental strain over a one-hour period. EMG was recorded from frontalis,
      temporalis, trapezius, and splenius capitis. Pain in the corresponding locations
      was recorded before the test, every 10 minutes during the test, and the 30-minute
      posttest period. RESULTS: The fibromyalgia patients developed pain during the
      test in all the above body locations. Pain development in all locations
      associated with trapezius EMG activity, but not with EMG activity in underlying
      muscles for forehead, temples, and neck. CONCLUSION: Stress-induced pain in
      fibromyalgia patients is not generally caused by muscle activity. The trapezius
      EMG response may be part of a general stress response that cause pain
      independently of motor activity in muscles.

PMID- 11324797
TI  - Do undereducated patients read and understand written education materials? A
      pilot study in Isparta, Turkey.
AB  - OBJECTIVES: The aim of our study is to evaluate the effect of written information
      in improving the knowledge of the undereducated nonsteroidal anti-inflammatory
      drug (NSAID) users about the side effects of NSAIDs and to investigate the
      compliance of patients with the written information materials. METHODS: Thirty
      patients received only verbal information, 38 patients received only written, and
      40 patients received both verbal and written information. After seven or ten days
      a questionnaire was administered to the patients on the phone to assess the
      patients' knowledge. RESULTS: Sixty one (78.2%) patients read the leaflets.
      Higher number of correct answers was obtained with both verbal and written
      information. Written information better informed than verbal information alone
      (p=0.02). CONCLUSION: We conclude that the undereducated patients will read and
      understand written education materials especially when the materials are written
      simple and short.

PMID- 11324798
TI  - Progress in cardioangioscopy.

PMID- 11324799
TI  - Novel method for assessing myocardial perfusion: visualization and measurement of
      intramyocardial coronary blood flow in the entire left ventricular wall using
      contrast enhanced, high frequency Doppler echocardiography.
AB  - Using a high frequency ultrasonic transducer, intramyocardial coronary blood flow
      (IM-CBF) can be visualized and evaluated during hemodynamic changes in the
      anterior wall and septum of the left ventricle (LV). We tested the hypothesis
      that detection and quantitative measurement of IM-CBF of entire LV segments are
      feasible using a high frequency ultrasonic transducer in conjunction with
      intravenous contrast injection in vivo. A 3 - 8 MHz transducer was used to image
      and measure IM-CBF in 10 anesthetized dogs. We obtained a color Doppler image of
      IM-CBF in the LV short-axis view after intravenous Levovist injection (25 mg/ml).
      The IM-CBF velocity was recorded using spectral Doppler in the antero-septal and
      infero-posterior wall of closed chest dogs and in the entire LV after opening the
      chest. A significant increase in IM-CBF velocity was observed in all LV regions
      after adenosine 5'- triphosphate (ATP) administration. After Levovist(TM)
      injection, the visualization of IM-CBF was improved and the spectral Doppler
      pattern of coronary flow velocity was clarified compared to baseline. IM-CBF was
      assessed in the antero-septal region of the LV before and after left anterior
      descending coronary artery occlusion. A high frequency ultrasonic transducer in
      conjunction with intravenous contrast injection improved IM-CBF visualization,
      enabling quantitative evaluation of the intramyocardial coronary circulation in
      the entire LV after coronary occlusion and hyperemia. This study may represent a
      step towards noninvasive assessment of myocardial perfusion before and after
      coronary reperfusion.

PMID- 11324800
TI  - Effects of nonionic contrast media on platelet aggregation: assessment by
      particle counting with laser-light scattering.
AB  - Intravascular radiographic contrast media used in angiography, particularly
      nonionic contrast media, may cause activation of platelets. This study was
      designed to determine which properties of nonionic contrast media were
      potentially responsible for this action. Platelet aggregation after adenosine
      diphosphate stimulation was studied in the platelet rich plasma obtained from 37
      patients who underwent left ventriculography using the highly sensitive method of
      particle counting with laser-light scattering. Platelet activation by contrast
      media was studied in the platelet rich plasma from healthy volunteers using flow
      cytometric analysis to detect platelet degranulation as P-selectin expression.
      There was a significant decrease in platelet aggregation in patients injected
      with ioxilan or iomeprol compared with patients injected with iohexol. There was
      a significant increase in P-selectin expression with the three groups of contrast
      media compared to control. The platelet activation with ioxilan or iomeprol was
      significantly less compared to the activation with iohexol. The comparison showed
      that previous generalization regarding platelet activation by nonionic contrast
      media might not be valid. It is presumed that the higher osmolality of iohexol
      may contribute to the increase in platelet aggregation and activation.

PMID- 11324801
TI  - OPC-8212, a quinoline derivative, counteracts the reduction in type III collagen
      mRNA due to lipopolysaccharides in cultured rat cardiac fibroblasts.
AB  - Fibrillar collagen plays an essential role in ventricular remodeling, which is a
      major prognostic factor in various heart diseases. Inflammatory cytokines,
      including tumor necrosis factor alpha (TNFalpha), have been reported to play a
      role in various heart diseases and OPC-8212, a quinolinone derivative, has been
      demonstrated to reduce TNFalpha production. No studies have examined the effects
      of OPC-8212 on collagen metabolism in connection with inflammatory cytokine and
      growth factors. Using lipopolysaccharides as a tool to enhance TNFalpha, we
      examined the effects of OPC-8212 on the expression of type III collagen mRNA
      [alpha1(III)] in cultured neonatal rat cardiac fibroblasts. We also measured the
      concentration of TNFalpha and transforming growth factor beta (TGFbeta) in the
      cultured medium. Northern blot analysis revealed that LPS reduced the expression
      of alpha1(III) mRNA, and OPC-8212 counteracted this reduction (on average 25%
      above the reduced level by LPS stimulation). LPS enhanced the TNFalpha
      concentration in the medium, and OPC-8212 inhibited this enhancement. LPS
      increased the TGF-beta1 concentration in the cultured medium, while OPC-8212 did
      not affect this increase. In summary, OPC-8212 counteracted the reduction in type
      III collagen mRNA expression by LPS accompanied by suppression of the increase in
      TNFalpha.

PMID- 11324802
TI  - Multiple coronary artery aneurysms combined with abdominal aortic aneurysm.
AB  - Coronary artery aneurysm (CAA) is defined as coronary dilatation which exceeds
      the diameter of a normal adjacent segment or the diameter of the patients's
      largest coronary vessel by as much as 1.5 times. It is an uncommon pathology with
      a frequency of 1-4% in routine autopsies or coronary angiographies.
      Atherosclerosis plays an important role in the development of CAA, and it may be
      a predominant cause in the majority of patients. However, the timing of surgical
      intervention and the treatment options for CAA are still controversial. In this
      report, we present a patient who had multiple CAAs of all main coronary arteries
      and abdominal aortic aneurysm. Different treatment modalities and indications are
      also discussed.

PMID- 11324803
TI  - Genetic background in patients with acute myocardial infarction.
AB  - The renin-angiotensin system is believed to play important roles in the
      development of acute myocardial infarction, and gene polymorphisms may also be
      involved. To investigate the genetic background in patients with acute myocardial
      infarction, we performed a case control study in a Japanese population. The study
      included 150 patients with acute myocardial infarction and 150 healthy, age- and
      sex-matched controls. We examined polymorphisms of angiotensin II type 1 receptor
      (1 166 A / C), type 2 receptor (3123 C / A), and bradykinin B2 receptor (-58 T /
      C) in these subjects. The allelic frequencies of angiotensin II type I receptor C
      and angiotensin II type 2 receptor A were significantly higher in the acute
      myocardial infarction subjects than in the control subjects, and this tendency
      was more significant in the younger patients. The combined ratios of angiotensin
      II type 1 receptor C and type 2 receptor A alleles in patients under 64 years old
      were significantly higher than in their older counterparts. However the total
      numbers of conventional coronary risk factors (hypertension,
      hypercholesterolemia, diabetes mellitus, and smoking) in individual subjects were
      not significantly different between younger and older patients. These
      polymorphisms were found to be involved in the development of acute myocardial
      infarction, particularly in the younger patients, and it was concluded that the
      incidence of acute myocardial infarction might be reduced by management from the
      genotypes.

PMID- 11324804
TI  - Impaired exercise-related myocardial uptake of technetium-99m-tetrofosmin in
      relation to coronary narrowing and diabetic state: assessment with quantitative
      single photon emission computed tomography.
AB  - Despite the diagnostic efficacy of stress myocardial perfusion imaging, the
      correlation between the actual perfusion tracer activity and diseased state of a
      coronary artery has not been studied in detail. We estimated exercise-related
      perfusion augmentation in relation to disease states of a coronary artery in
      diabetic and non-diabetic patients by a newly developed quantitative technetium
      (Tc)-99m-tetrofosmin myocardial imaging technique. Tc-99m-tetrofosmin tomographic
      imaging with an exercise-rest protocol was performed in 26 stable coronary
      patients and in 8 age-matched controls. Percent increase (%IR) in myocardial
      count during symptom-limited submaximal exercise-stress was calculated in 16 non
      infarcted polar map segments and in each coronary territory by a subtraction
      technique with corrections for physical decay and injected tracer doses, and the
      results were compared with those of angiographically quantified coronary diameter
      stenosis (%DS). Percent IR and peak heart rate during exercise showed a positive
      linear correlation both in coronary territories with significant stenosis (%DS >
      or = 75%) and in control or nonstenotic (%DS < 75%) territories. The regression
      line in stenotic regions was, however. significantly (p < 0.01) shifted downward
      compared to that in non-stenotic regions. Percent IR in stenotic regions showed a
      significant inverse correlation with %DS. Coronary stenosis of 75% or more was
      identified by a %IR cutoff value of 40% with 77% sensitivity, 70% specificity,
      and an accuracy of 72%. In coronary territories with a %DS of less than 75%, %IR
      in diabetic patients was significantly lower (46+/-15%) than that in nondiabetic
      patients (61+/-25%). Thus, blunted exercise-related augmentation of myocardial
      uptake of Tc-99m-tetrofosmin correlates with the severity of coronary narrowing
      and diabetic state.

PMID- 11324805
TI  - Comparison of ticlopidine and cilostazol for the prevention of restenosis after
      percutaneous transluminal coronary angioplasty.
AB  - Prevention of restenosis after percutaneous transluminal coronary angioplasty
      (PTCA) continues to be a significant problem. Recent controlled studies have
      demonstrated that cilostazol suppresses restenosis after PTCA. The effects of
      ticlopidine, another antiplatelet agent, were compared in terms of outcomes of
      patients randomized for treatment with the two drugs after PTCA. A total of 35
      patients (47 lesions) were assigned prospectively and randomly to ticlopidine (17
      patients, 24 lesions) and cilostazol (18 patients, 23 lesions) groups. Minimal
      luminal diameter (MLD) and percentage of stenosis to reference diameter were
      estimated before PTCA, just after the procedure and after 4 months follow-up. All
      patients underwent 4 months angiographic follow-up, at the end of which MLD was
      2.03+/-0.71 mm in the ticlopidine group and 2.05+/-0.68 mm in the cilostazol
      group (p = 0.95), and the percentage of stenosis to reference diameter was 31.4+/
      16.7% and 30.0+/-17.0%, respectively (p = 0.78). The restenosis rate was 12.5% in
      the ticlopidine group and 17.4% in the cilostazol group (p = 0.69), relatively
      low as compared to the 20% to 30% reported in previous studies. Adverse drug
      reactions during the follow-up period were observed in two of the ticlopidine
      group and none of the cilostazol group. We conclude that both ticlopidine and
      cilostazol are effective for the prevention of restenosis after PTCA, however the
      former may be associated with slight side effects.

PMID- 11324806
TI  - Serum lipoprotein(a) and its relation to left ventricular thrombus in patients
      with acute myocardial infarction.
AB  - It is well known that the incidence of left ventricular (LV) thrombosis is high
      in patients with acute myocardial infarction (AMI). Due to the high degree of
      structural homology with plasminogen, lipoprotein(a) may produce thrombogenic
      effects by modulating the fibrinolytic system. However, the role of Lp(a) level
      in the formation of LV thrombus has not been studied. This study sought to
      determine whether Lp(a) is a risk factor for LV thrombus in patients with AMI. We
      have analyzed clinical, echocardiographic and biochemical data in 102 consecutive
      patients (aged 58+/-12 years, 92 men / 10 women) with first anterior AMI. Two
      dimensional examination was performed on days 1, 3, 7, 15, and 30. Blood samples
      were obtained within 12 h after the onset of symptoms and before beginning the
      therapy. Plasma levels of fibrinogen and Lp(a) were measured using enzyme-linked
      immunosorbent assay and immunonephelometric methods, respectively. LV thrombus
      was detected in 20 (20.3%) patients. No significant difference was found for
      admission Lp(a) levels between patients with or without thrombus (30.5+/-17.2 vs
      32.3+/-22.4 mg/dl, p = 0.7). Univariate analysis showed that patients with LV
      thrombus had a higher wall motion score index (1.8+/-0.3 vs 1.4+/-0.3, p =
      0.002), a higher peak creatine kinase level (2945+/-898 vs 1805+/-1336, I / U p =
      0.004), a larger end-diastolic volume (139.7+/-38.6 vs 114.1+/-41.8 ml, p =
      0.04), a larger end-systolic volume (83.1+/-34.3 vs 59.2+/-30.6 ml, p = 0.02 ),
      and a lower ejection fraction (38+/-12 vs 47+/-11, p = 0.04). In multivariate
      analyses, only peak creatine kinase level (p = 0.04) and LV wall motion score
      index (p = 0.002) were independent predictors of left ventricular thrombus
      formation. These results suggest that Lp (a) is not a risk factor for LV thrombus
      in patients with AMI. Our data demonstrate that the best predictors of LV
      thrombus formation after AMI are a high peak creatine kinase level and a high LV
      wall motion score index.

PMID- 11324807
TI  - Underutilization of anticoagulation therapy in chronic atrial fibrillation.
AB  - Atrial fibrillation, the most common chronic arrhythmia, results in an increased
      risk of stroke. Anticoagulation therapy can reduce this risk, but appears to be
      underused. The objective of this study was to examine the use of warfarin and
      prevalence of stroke in patients with rheumatic, nonrheumatic valvular and
      nonvalvular atrial fibrillation. Between January 1993 and December 1998, 457
      chronic atrial fibrillation patients with continuous follow-up in our hospital
      were identified as having rheumatic heart disease (n = 114): nonrheumatic
      valvular disease (n = 65); or nonvalvular disease (n = 278). Warfarin was used
      less often in patients with nonrheumatic valvular (16.7%) and nonvalvular
      diseases (20.1%) than in those with rheumatic heart disease (81.6%, p < 0.001).
      In contrast, the prevalence of stroke among patients with nonvalvular disease was
      40.3% which was similar to the 33.3% found in patients with rheumatic heart
      disease but significantly higher than the 24.6% found in patients with
      nonrheumatic valvular disease (p < 0.05). A history of stroke did not alter the
      trend of use of warfarin among the three groups of patients. Only 20.6% of
      patients on warfarin received monthly monitoring of prothrombin time. In
      conclusion, the anticoagulation therapy in our patients with chronic atrial
      fibrillation, regardless of their associated valvular diseases, is significantly
      underutilized. This underuse could account for a high prevalence of stroke. This
      risk of stroke, however, is less in patients with nonrheumatic valvular discase
      than in those with nonvalvular atrial fibrillation.

PMID- 11324808
TI  - Abrupt loss of constant fusion during entrainment of ventricular tachycardia at a
      critical paced cycle length.
AB  - Sustained monomorphic ventricular tachycardia (VT) can be frequently entrained
      and interrupted with rapid pacing and the mechanism of the pacing-induced
      interruption is considered to be due to orthodromic block. This study focused on
      the incidence of VT which was interrupted at a critical cycle length and was
      characterized by an abrupt loss of constant fusion in the surface
      electrocardiogram (ECG), and the role of orthodromic block as the cause of such
      characteristic change and interruption of VT was analyzed. Among 45 consecutive
      patients with symptomatic VT, rapid pacing was performed in 43 VTs of 39
      patients. The exit was mapped as the earliest site of the activation during VT
      and an electrode catheter was located at the site. Rapid pacing was performed at
      progressively shorter cycle lengths in steps of 10 msec until VT was interrupted
      and the timing of the orthodromic and direct capture was compared at the exit.
      Abrupt loss of constant fusion was observed in 25 of 39 patients (64.1%): and the
      loss was invariably associated with interruption of VT. When the timings of the
      activation of the exit were compared, which were measured from the preceding (n
      1) stimulus as the time reference, the direct capture was relatively delayed
      compared to that of the orthodromic capture. This finding suggests that
      orthodromic block is the cause of the direct capture as well as the pacing
      induced interruption of VT. In the remaining 13 patients (35.9%), the surface ECG
      showed a gradual transition into the fully paced QRS morphology. The direct
      capture was confirmed in the non-fused beats, but it was not necessarily
      associated with interruption of VT. The interval from the stimulus to the
      entrained electrogram at the exit showed a gradual prolongation until the exit
      was finally captured directly from the pacing site. The confirmation of constant
      fusion followed by abrupt loss in ECG can be a reliable hallmark of orthodromic
      block as the cause of the interruption of VT during transient entrainment at a
      critical paced cycle length.

PMID- 11324809
TI  - Effects of cavotricuspid isthmus catheter ablation on paroxysmal atrial
      fibrillation.
AB  - It has been demonstrated that successful cavotricuspid isthmus ablation of
      typical atrial flutter combined with atrial fibrillation (AF) sometimes
      influences the preablation history of paroxysmal AF. However, the effectiveness
      of only isthmus ablation on AF itself is unclear. Endocardial catheter mapping
      during induced AF was performed around the tricuspid annulus using duodecapolar
      clectrode catheters in 39 patients with drug-refractory paroxysmal AF. Isthmus
      ablation was performed in 16 patients (41%) in whom catheter mapping during AF
      showed an organized activation pattern around the tricuspid annulus. During a
      mean follow-up of 12.3 months, isthmus ablation was successful in preventing AF
      in 12 (75%) patients, 8 without medication and 4 with a previously ineffective
      drug. This success group had a significantly higher F wave amplitude in lead V1
      (0.29+/-0.10 vs 0. 15+/-0.04 mV, p < 0.01), a higher left ventricular ejection
      fraction (74+/-9 vs 58+/-2%, p < 0.05), and a smaller left atrial dimension (35+/
      6 vs 43+/-4 mm, p < 0.05) than the failure group. Isthmus ablation may be
      effective in preventing paroxysmal AF with an organized activation pattern around
      the tricuspid annulus. F wave amplitude, left ventricular ejection fraction, and
      left atrial dimension were significant predictors of success.

PMID- 11324810
TI  - Clinical features and prognosis of acute aortic intramural hemorrhage compared
      with those of acute aortic dissection: a single center experience.
AB  - The clinical manifestations and natural history of acute aortic intramural
      hemorrhage are not well characterized. Therefore, we have evaluated the
      differences in the clinical features and prognosis between acute intramural
      hemorrhage and acute classic aortic dissection. One hundred two consecutive
      patients with acute aortic syndrome were diagnosed between November 1994 and May
      1999. The clinical features, treatment modalities and survival of these patients
      were analyzed. Thirty one of the 102 patients (30%) had intramural hemorrhage and
      71 (70%) had aortic dissection. Patients with intramural hemorrhage were older
      than those with aortic dissection (mean ages 67 and 55 years, respectively) (p <
      0.001), and intramural hemorrhage showed a lower proportion of type A than did
      aortic dissection (32% and 58%, respectively) (p = 0.018). The incidence of
      severe complications was significantly lower in patients with intramural
      hemorrhage than in those with aortic dissection (19% and 27%, respectively) (p <
      0.001). Mean follow-up duration was 23.1+/-16.0 months. The overall death rate
      for patients with intramural hemorrhage (2 / 31; 6%) tended to be lower than
      those with aortic dissection (14 / 71; 20%) (p = 0.104). The Stanford
      classification and treatment modalities were not correlated with death. Late
      follow-up imaging studies in intramural hemorrhage showed partial to complete
      resolution of intramural hematoma (9 / 15; 60%). In this study, intramural
      hemorrhage was fairly common, more frequent among older patients, had a lower
      proportion of type A, and showed a lower incidence of severe complications and a
      more favorable prognosis in terms of mortality, than aortic dissection.

PMID- 11324811
TI  - Histopathology of viremia-associated ana-aki-byo in combination with Aeromonas
      hydrophila in color carp Cyprinus carpio in Japan.
AB  - A disease in which 'viremia-associated ana-aki-byo' is combined with an Aeromonas
      hydrophila infection currently occurs and is highly transmissible in color carp
      Cyprinus carpio in Japan. In the present study, to determine the interrelation
      between a corona-like virus and A. hydrophila, we conducted transmission trials
      by cohabiting naturally diseased carp with healthy carp with skin that had been
      slightly damaged artificially. Experimentally exposed fish successfully
      replicated the combination of a corona-like viral viremia and A. hydrophila
      infection. Diseased carp displayed scale-sac edema, ascites and exophthalmus
      adding to the formation of skin ulcers. In addition to pathological changes due
      to the corona-like virus infection, various changes due to the A. hydrophila
      infection occurred. Anasarcous skin lesions exhibited a separated epidermis,
      expanded scale-sacs, and an edematous dermis accompanied by hemorrhage and
      necrosis. The underlying lateral musculature was edematous and possessed markedly
      atrophied muscle fibers. Hepatocytes were either atrophied or swollen and had a
      granular appearance. Renal tubular cells showed vacuolar degeneration, cloudy
      swelling, necrosis and destruction. Hemosiderin deposition occurred within
      macrophages in the spleen and hematopoietic tissue, and within hepatocytes.
      Cardiac muscle fibers exhibited degeneration and necrosis accompanied by
      hemorrhage in the myocardium of heart. These changes appeared to be induced by
      bacterial toxins because bacterial cells did not directly invade these affected
      tissues.

PMID- 11324812
TI  - Characterization of attenuated Renibacterium salmoninarum strains and their use
      as live vaccines.
AB  - Two nutritionally mutant strains of Renibacterium salmoninarum (Rs) were isolated
      that grew on tryticase soy agar (Rs TSA1) or brain heart infusion agar (Rs BHI1).
      These 2 strains could be continuously cultured on these media, whereas typical R.
      salmoninarum would only grow on KDM-2 agar. We determined no other phenotypic
      difference that could be used to distinguish them from wild-type R. salmoninarum.
      Both strains were found to be avirulent when 5 x 10(6) bacteria were
      intraperitoneally (i.p.) injected into Atlantic salmon. Rs TSA1, Rs BHI1, and Rs
      MT-239 (a R. salmoninarum strain previously shown to be attenuated) were tested
      as live vaccines in 2 separate trials. The best protection was seen with Rs TSA1.
      Vaccinated Atlantic salmon had relative percent survival (RPS) of 50 at 74 d post
      challenge in Trial 1 and 76 at 60 d post-challenge in Trial 2. In both trials,
      100% of the control salmon died from bacterial kidney disease (BKD) (within 40 d
      for Trial 1 and 50 d for Trial 2) after i.p. challenge with 5 x 10(6) live cells
      of the virulent isolate Rs Margaree.

PMID- 11324813
TI  - Seasonal occurrence of Dollfustrema vaneyi (Digenea: Bucephalidae) metacercariae
      in the bullhead catfish Pseudobagrus fulvidraco in a reservoir in China.
AB  - The seasonal population dynamics of metacercariae of the bucephalid Dollfustrema
      vaneyi (Tseng, 1930) Echmann, 1934 in the bullhead catfish Pseudobagrus
      fulvidraco (Richardson) were investigated in Jiangkou reservoir, Jiangxi
      Province, east China, during the period from April 1990 to August 1991. In total,
      523 fish were obtained, and the overall prevalence of the metacercariae was
      89.87% and mean abundance 136.25 +/- 308.09 (mean +/- SD). A pattern of seasonal
      changes in prevalence and mean abundance was observed, with higher levels of
      metacercariae infection in late spring and summer. An analysis of the
      distribution of D. vaneyi in different organs of P. fulvidraco suggested that the
      eyes might be a suitable location for the parasite. Furthermore, the possible
      role of metacercariae in bullhead catfish was discussed in relation to the life
      cycle of this parasite.

PMID- 11324814
TI  - Treatment of Microcotyle sebastis infestation in cultured rockfish Sebastes
      schlegeli by oral administration of praziquantel in combination with cimetidine.
AB  - The effect of cimetidine on the treatment efficacy of praziquantel against
      Microcotyle sebastis infestation in cultured rockfish Sebastes schlegeli was
      investigated. Juvenile rockfish were divided into 7 groups, and orally
      administered praziquantel alone (50, 100 and 200 mg kg(-1) body wt, BW) or in
      combination with cimetidine at a dose of 200 mg kg(-1) BW for each praziquantel
      dose. The fish in the control group were administered only saline. The results
      clearly showed that coadministration of cimetidine with praziquantel led to a
      significantly increased treatment efficacy of the latter drug, and consequently
      would lead to a lowering of the total dose of praziquantel, and a reduction in
      the administration times and costs for the treatment of M. sebastis infestation
      in cultured rockfish.

PMID- 11324815
TI  - Ultrastructural characterisation of Marteilia species (Paramyxea) from Ostrea
      edulis, Mytilus edulis and Mytilus galloprovincialis in Europe.
AB  - A focused ultrastructural study of Marteilia spp. found in cultured Ostrea
      edulis, Mytilus edulis and Mytilus galloprovincialis from France and Spain was
      conducted with emphasis placed on haplosporosomes, striated plate-like inclusions
      and spore wall morphology. Two types of haplosporosome were identified, sphaeroid
      and oblate, which were common to the parasite in all 3 host species. A total of
      492 haplosporosomes were measured; those from the Marteilia sp. in Mytilus spp.
      were marginally smaller than those in Ostrea edulis. Spore wall morphology was
      found to vary depending on the state of maturity of the parasite--the more mature
      the parasite, the thicker the wall surrounding it. It is suggested that the
      current criteria used to distinguish M. maurini from M. refringens are invalid
      and that M. maurini was relegated to a junior synonym of M. refringens.

PMID- 11324816
TI  - First record of Marteilia sp. in mussels Mytilus galloprovincialis in Croatia.
AB  - Marteiliosis is a disease of molluscs caused by Marteilia refringens in Europe
      and M. sydneyi in Australia. During routine examination of cultured mussels
      Mytilus galloprovinciallis in the northern Adriatic, the occurrence of Marteilia
      sp. was recorded with a prevalence of 5%. This parasite was not detected in flat
      oysters reared in the same area. The affiliation of the detected parasite in M.
      galloprovinciallis was confirmed by in situ hybridization using a M. refringens
      probe, specific at the genus level. DNA of these infected mussels originating
      from the same area will be used to clarify the taxonomic position of this species
      within the genus Marteilia using a molecular approach.

PMID- 11324817
TI  - Increase in number and size of kidney concretions as a result of PCP exposure in
      the freshwater snail Planorbarius corneus (Gastropoda, Pulmonata).
AB  - Molluscan kidneys are able to excrete solids in the urine in the form of
      concretions. It is thought that increased formation of these concretions occur
      under pollutant, environmentally or reproductive induced stress. This study
      examined the formation of concretions in the kidney of the freshwater snail
      Planorbarius corneus L. experimentally exposed to pentachlorophenol (PCP). Light
      microscopic histopathological analysis of the PCP-exposed P. corneus revealed
      significantly enhanced production of the kidney concretions when compared to the
      kidneys of control individuals. Measurements of the number of kidney concretions,
      the apparent area of the concretions, and the epithelial area filled with
      concretions indicated an increase in the number and size of concretions in all
      treated snails. Lipofuscin content of excretory cell concretions was detected.

PMID- 11324818
TI  - DNA fragmentation, an indicator of apoptosis, in cultured black tiger shrimp
      Penaeus monodon infected with white spot syndrome virus (WSSV).
AB  - Fifty black tiger shrimp Penaeus monodon from commercial cultivation ponds in
      Malaysia were examined by Tdt-mediated dUTP nick-end labeling (TUNEL)
      fluorescence assay and agarose gel electrophoresis of DNA extracts for evidence
      of DNA fragmentation as an indicator of apoptosis. From these specimens, 30 were
      grossly normal and 20 showed gross signs of white spot syndrome virus (WSSV)
      infection. Of the 30 grossly normal shrimp, 5 specimens were found to be positive
      for WSSV infection by normal histology and by nested polymerase chain reaction
      (PCR) analysis. All of the specimens showing gross signs of WSSV infection were
      positive for WSSV by normal histology, while 5 were positive by nested PCR only
      (indicating light infections) and 15 were positive by 1-step PCR (indicating
      heavy infections). Typical histological signs of WSSV infection included nuclear
      hypertrophy, chromatin condensation and margination. None of the 25 grossly
      normal shrimp negative for WSSV by 1-step PCR showed any signs of DNA
      fragmentation by TUNEL assay or agarose gel electrophoresis of DNA extracts. The
      10 specimens that gave PCR-positive results for WSSV by nested PCR only (i.e., 5
      grossly normal shrimp and 5 grossly positive for WSSV) gave mean counts of 16 +/-
      8% TUNEL-positive cells, while the 25 specimens PCR positive by 1-step PCR gave
      mean counts of 40 +/- 7% TUNEL-positive cells. Thus, the number of TUNEL positive
      cells present in tissues increased with increasing severity of infection, as
      determined by gross signs of white spots on the cuticle, the number of
      intranuclear inclusions in histological sections, and results from single and
      nested PCR assays. DNA extracts of PCR-positive specimens tested by agarose gel
      electrophoresis showed indications of DNA fragmentation either as smears or as
      200 bp ladders. Given that DNA fragmentation is generally considered to be a
      hallmark of apoptosis, the results suggested that apoptosis might be implicated
      in shrimp death caused by WSSV.

PMID- 11324819
TI  - Detection and quantification of infectious hypodermal and hematopoietic necrosis
      virus in penaeid shrimp by real-time PCR.
AB  - A real-time PCR method using a fluorogenic 5' nuclease assay and a PE Applied
      Biosystems GeneAmp 5700 sequence detector was developed to detect infectious
      hypodermal and hematopoietic necrosis virus (IHHNV) in penaeid shrimp. A pair of
      PCR primers to amplify an 81 bp DNA fragment and a fluorogenic probe (TaqMan
      probe) were selected from ORF1 (open reading frame 1) of the IHHNV genome. The
      primers and TaqMan probe used in this assay were shown to be specific for IHHNV
      and did not react with either hepatopancreatic parvovirus (HPV), white-spot
      syndrome virus (WSSV), or shrimp DNA. A plasmid, pIHHNV-P4, containing the target
      IHHNV sequence was constructed and used as a positive control. The concentration
      of pIHHNV-P4 was determined through spectrophotometric analysis and the plasmid
      was used for quantitative studies. This real-time PCR assay had a detection limit
      of 10 copies and a log-linear range up to 5 x 10(7) copies of IHHNV DNA. The
      assay was then used to quantify IHHNV in infected shrimp collected from 5
      locations: Hawaii, Panama, Mexico, Guam, and the Philippines. The quantitative
      analysis showed that wild-caught, large juvenile Penaeus stylirostris collected
      from the Gulf of California (Mexico) in 1996 were naturally infected with IHHNV
      and contained up to 10(9) copies of IHHNV microg(-1) of DNA. Similar quantities
      of IHHNV were detected in hatchery-raised, small juvenile P. stylirostris
      collected from Guam in 1995 and in farm-raised, post-larval P. monodon from the
      Philippines in 1996. Laboratory-infected P. stylirostris contained approximately
      10(8) copies of IHHNV 31 d after being fed with IHHNV-infected shrimp tissue. In
      contrast, individuals of Super Shrimp, a line of P. stylirostris selected for
      IHHNV resistance, showed no signs of infection 32 d after ingesting IHHNV
      infected shrimp tissue. Laboratory-infected P. vannamei also contained
      approximately 10(8) copies of IHHNV 30 d after being fed infected shrimp tissue.
      A time-course study of IHHNV replication in juvenile P. vannamei showed that the
      doubling time in the exponential growth phase was approximately 22 h.

PMID- 11324820
TI  - Detection of hepatopancreatic parvovirus (HPV) of penaeid shrimp by in situ
      hybridization at the electron microscope level.
AB  - A post-embedding in situ hybridization procedure was developed to detect
      hepatopancreatic parvovirus (HPV) of penaeid shrimp at the ultrastructural level.
      The procedure was optimized using sections of resin-embedded hepatopancreas from
      HPV-infected juvenile Penaeus monodon and postlarval P. chinensis. The
      hepatopancreata were fixed using various fixatives, dehydrated, and embedded in
      the hydrophilic resin Unicryl. A 592 bp HPV-specific DNA probe, labeled with DIG
      11-dUTP, was tested both on semi-thin and ultra-thin sections and examined by
      light and electron microscopy, respectively. Hybridized probe was detected by
      means of an anti-DIG antibody conjugated to 10 nm gold particles and subsequent
      silver enhancement. Hybridization signal intensities were similar with all
      fixatives tested, but ultrastructure was best preserved with either 2 or 6%
      glutaraldehyde. Post-fixation with 1% osmium tetroxide improved ultrastructure
      but markedly decreased hybridization signal and induced non-specific deposition
      of gold and silver. Under optimized conditions, this technique was used to
      successfully follow the development of HPV from absorption and transport through
      the cytoplansm to nuclear penetration, replication and release by cytolysis. The
      probe signal was consistently observed among necrotic cell debris within the
      lumen of hepatopancreatic tubules, within the microvillous border of tubule
      epithelial cells, within the cytoplasm, and within diagnostic HPV intranuclear
      inclusion bodies. The nucleolus and karyoplasm of patently infected cells (i.e.,
      showing HPV intranuclear inclusion bodies) were almost devoid of signal. Electron
      lucent structures, known as intranuclear bodies, commonly found within the
      virogenic stroma, showed only weak labeling. This is the first use of in situ
      hybridization to detect HPV nucleic acids with the electron microscope. The
      technique should be useful for studying the pathogenesis of HPV.

PMID- 11324821
TI  - Histone-like protein: a novel method for measuring stress in fish.
AB  - We assessed the effect of chronic stress using a group of potent, broad-spectrum
      antimicrobial polypeptides, called histone-like proteins (HLPs), which appear to
      be an important component of non-specific immunity in channel catfish Ictalurus
      punctatus skin. An enzyme-linked immunosorbent assay (ELISA) was developed to
      measure the predominant HLP (HLP-1) in channel catfish skin. Catfish were then
      exposed to a chronic stress consisting of overcrowding and elevated ammonia.
      Healthy unstressed fish had consistently high HLP-1 levels, but fish that had
      been stressed for 1 wk had significantly depressed HLP-1 levels; HLP-1 levels
      declined further in fish stressed for 3 or 4 wk. The time-dependent decline in
      HLP-1 levels was not accompanied by any gross signs of disease. In contrast to
      HLP-1 levels, antibacterial activity in the skin was significantly greater in
      fish stressed for 1 wk compared with unstressed fish; in addition, antibacterial
      activity was the same in fish that were unstressed or stressed for 3 or 4 wk.
      This suggests that other antibiotics besides HLP-1 may be induced in the skin,
      especially during early stages of stress, that may compensate for depressed HLP-1
      levels. Our results indicate that chronic stress has a significant suppressive
      effect on HLP-1 levels in channel catfish skin. The reduction of HLP-1 in the
      absence of clinical signs of disease, combined with evidence that its levels are
      not affected by the acute stressors of capture or sampling, suggests that HLP
      levels may be a promising indicator for monitoring fish health.

PMID- 11324822
TI  - Playing with evolution requires planning.

PMID- 11324823
TI  - Viral load, viral phenotype modification, zidovudine susceptibility and reverse
      transcriptase mutations during the first 6 months of zidovudine monotherapy in
      HIV-1-infected people.
AB  - We studied 14 zidovudine-naive, HIV-1-infected patients attending an infectious
      diseases clinic in Milan during zidovudine therapy for 6 months. We monitored CD4
      cell counts, immune complex-dissociated p24 antigen, viral phenotype and viral
      load in plasma. The virus infecting a subset of patients was examined for
      zidovudine susceptibility and zidovudine resistance-associated mutations. A
      significant correlation was established between the increase in the CD4 cell
      count and the decrease in viral load (Spearman's coefficients < -0.5). Patients
      who were p24 antigen positive had a higher viral load (P < 0.005 at baseline and
      after 6 months of therapy). Patients with non-syncytium-inducing (NSI) virus had
      higher CD4 cell counts over time than those with syncytium-inducing (SI) virus.
      We also examined the viral load in relation to viral phenotype. The median viral
      load in patients with NSI virus was higher than in SI controls at baseline, but
      not after 3 and 6 months of therapy. Sequential isolates of HIV-1 were obtained
      from nine patients and tested for resistance to zidovudine by monitoring the drug
      susceptibility and the reverse transcriptase-encoding sequence. Amino acid
      changes at codons 70 and 215 were present in some but not all isolates with
      zidovudine-resistant phenotype in vitro. It was possible to perform a correlation
      between zidovudine susceptibility and zidovudine-associated pol gene mutations
      only at the 6-month time point (Spearman's coefficient = 0.076). SI phenotype was
      associated with the development of a decreased zidovudine susceptibility. A
      correlation between zidovudine-associated pol gene mutations and SI phenotype was
      detected at the 6-month time point.

PMID- 11324824
TI  - Plasma HIV-1 RNA as a predictor of the efficacy of adding zalcitabine to a
      previous regimen with zidovudine.
AB  - The objective of this study was to determine whether or not plasma HIV-1 RNA
      levels, the syncytium-inducing phenotype assay or mutations at codon 215 of the
      gene encoding HIV-1 reverse transcriptase could have prognostic value in patients
      already undergoing therapy with zidovudine who were started on combination
      therapy with zidovudine and zalcitabine. A prospective study was performed in 37
      HIV-1-infected individuals who had received at least 6 months (mean: 9 months;
      range: 6-24 months) of zidovudine to which zalcitabine was added. The mean
      initial CD4 cell count was 330 cells/mm3 (range: 20-520 cells/mm3). At baseline
      and at the end of the study (12 months), we analysed CD4 and CD8 cell counts,
      plasma HIV-1 RNA levels, the syncytium-inducing phenotype of virus isolated from
      peripheral blood mononuclear cells and mutations at codon 215 of the gene
      encoding reverse transcriptase. These variables were studied by Fisher's exact
      and U Mann-Whitney tests. There were statistically significant differences
      between progressor and non-progressor groups at baseline and after a 12-month
      period in the following parameters: CD4 and CD8 cell counts and HIV-1 RNA level
      (P < 0.05). Clinical progression occurred significantly more often in patients
      with CD4 cell counts < or = 300 cells/mm3 and HIV-1 RNA > 30000 copies/ml at
      baseline (P = 0.003). Moreover, we found that progression to AIDS only occurred
      in those patients whose viral load increased during the follow-up period and who
      had a CD4 cell count < 300 cells/mm3. Our results show the usefulness of HIV-1
      RNA level as a surrogate marker for clinical outcome.

PMID- 11324825
TI  - Random important alterations in HIV-1 viral quasispecies after antiviral
      treatment.
AB  - The evolution of HIV-1 viral populations was studied in a set of MT-2-co-cultured
      viruses isolated from five patients at the beginning of treatment with zidovudine
      and after 11-36 months of drug therapy. We first characterized the HIV-1 pol gene
      to detect the zidovudine-resistance mutations at codons 215 and 219. To analyse
      the effect that the selective pressure of zidovudine on pol exerted on other
      genomic regions, we also studied the env gene. The env gene sequence of virus
      isolated from one individual was unchanged, whereas three other sample pairs had
      minor alterations in env. In one individual, we detected a significant change in
      the env gene sequence, and so performed a clonal analysis on viruses isolated
      before and after treatment. In this individual, the zidovudine-resistant variant
      that became predominant in the resistant virus population was an undetected
      minority variant of the viral population before treatment was initiated. These
      results indicate that the evolution of quasispecies produced by selective
      pressure on the pol gene from zidovudine treatment could select, in a random
      process, important changes in other genomic regions; in particular, we describe
      alterations in the env gene.

PMID- 11324826
TI  - Susceptibility of human cytomegalovirus to two-drug combinations in vitro.
AB  - Human cytomegalovirus (HCMV) is a major cause of morbidity and mortality for
      immunocompromised hosts. We sought to determine the in vitro susceptibility of
      HCMV reference laboratory strains, clinical isolates and strains with known
      resistance to currently available anticytomegaloviral drugs to two-drug
      combinations of the following compounds: ganciclovir, foscarnet, cidofovir and
      its cyclic congener, cyclic HPMPC (cHPMPC), and lobucavir. Cytotoxicity was
      determined by Trypan Blue exclusion of cells exposed both when proliferating (non
      confluent) and once confluent. Antiviral effect was determined by a plaque
      reduction assay in MRC-5 human embryonic lung cells. Drug interactions were
      determined by median-dose effect analysis with the combination index calculated
      at 50, 75, 90 and 95% inhibitory concentrations. No drug, either alone or in
      combination, reached a 50% cytotoxicity concentration in the dose ranges tested.
      Overall, 252/280 (90.0%) of the two-drug combinations demonstrated additive or
      synergistic interactive effects towards the panel of HCMV isolates tested. No
      combination demonstrated antagonism at all inhibitory concentrations to more than
      one isolate. Interestingly, the clinical isolate tested demonstrated the highest
      frequency of antagonistic combinations (3/10), as well as marked differences from
      pan-susceptible laboratory strains. The combinations of ganciclovir + foscarnet
      and cHPMPC + foscarnet demonstrated additive to synergistic effects against all
      isolates tested. In vitro combination drug studies could help in the rational
      choice of therapeutic regimens for use in clinical trials, potentially resulting
      in decreased toxicity, increased efficacy and delayed onset of drug resistance.

PMID- 11324827
TI  - Quantification of HIV-1 RNA during antiretroviral therapy: association with viral
      phenotype and development of resistance.
AB  - The aim of this study was to analyse the interplay between the treatment
      responses, as assessed by serum HIV-1 RNA levels and CD4 cell counts, virological
      phenotype and the development of phenotypic and genotypic resistance. A total of
      47 late-stage, HIV-1-infected, antiretroviral-naive patients treated with reverse
      transcriptase inhibitors (zidovudine or didanosine monotherapy or alternating
      zidovudine and didanosine) as part of a randomized study and remaining on
      treatment for a minimum of 1 year were included in the study. Baseline serum HIV
      1 RNA levels did not differ between the patients harbouring syncytium-inducing
      (SI) virus and those harbouring non-syncytium-inducing (NSI) virus (P = 0.66),
      despite the fact that the group of patients with SI virus had a significantly
      lower median CD4 cell count (P < 0.00005) and a higher proportion of patients
      diagnosed with AIDS at study entry (11/19 versus 6/25) than did the group with
      NSI virus. The patients harbouring SI virus had significantly faster clinical
      progression than that of the patients harbouring NSI virus (P < 0.001). The
      patients wit

PMID- 11324828
TI  - A comparison of serum HIV-1 RNA levels as measured by two quantitative assays in
      zidovudine-treated, asymptomatic, HIV-infected individuals.
AB  - HIV-1 RNA levels as measured by two commercially available quantitative assays
      were compared before and during zidovudine treatment. HIV-1 RNA levels were
      measured in stored serum samples from 24 Dutch zidovudine-treated participants of
      a zidovudine efficacy study (European-Australian Collaborative Group Study 017)
      at weeks -3, 0, 4 and 8, using quantitative nucleic acid sequence-based
      amplification (NASBA; Organon Technika) and quantitative reverse transcriptase
      polymerase chain reaction (Amplicor; Roche Molecular Systems). HIV-1 RNA copy
      numbers and changes from baseline as measured by each assay were compared.
      Individual responses to treatment were compared using definitions based on the
      within-subject variation of each assay. Before treatment, HIV-1 RNA levels as
      measured by NASBA were 0.49 logs higher than the levels measured by the Amplicor
      assay (95% confidence interval (CI) 0.32-0.66). During treatment, this difference
      decreased significantly to 0.27 logs (95% CI 0.01-0.53; difference 0.22 logs; 95%
      CI 0.05-0.37). The smaller difference between the results of the two assays
      during treatment was a consequence of a larger decline in RNA level as measured
      by NASBA compared with that measured by the Amplicor assay (mean change after 4
      weeks 0.77 and 0.49 logs, respectively). At week 8, the mean HIV-1 RNA level was
      still significantly below baseline values as measured by NASBA, but not when
      measured by the Amplicor assay. Discrepancies in individual responses as measured
      by the two assays were also observed. In conclusion, marked differences exist
      between the NASBA and Amplicor quantitative assays, in both HIV-1 RNA copy
      numbers without treatment and changes in RNA level during treatment. These
      differences should be considered in interpreting analyses of clinical trials and
      relationships between HIV-1 RNA level and clinical outcome, as well as in the use
      of RNA level in the management of HIV-infected patients.

PMID- 11324829
TI  - Rationale for early antiretroviral therapy in patients with CD4 cell counts > 500
      cells/mm3.

PMID- 11324830
TI  - Lessons from the corporate world.

PMID- 11324831
TI  - Doctoral students' responses to writing critique: messages for teachers.
AB  - Writing is a major part of learning scholarship in a discipline. Therefore, it is
      important to understand what promotes and what hinders this learning. In
      transcribed interviews, 15 doctoral students in nursing at a large university
      described to us what they saw as helpful or not helpful about responses to their
      writing. The themes take the form of messages for teachers that, when reported in
      the context of the composition literature, provide helpful suggestions for
      teachers.

PMID- 11324832
TI  - The transition to first position as nurse practitioner.
AB  - The nurse who graduates from a nurse practitioner program leaves a comfort zone
      of nursing practice to enter a new position where feelings of insecurity and
      stress are common. Because the role of the nurse practitioner (NP) continues to
      evolve and is influenced by many environmental issues, the preparation of the NP
      by the academic institution needs to be assessed on a frequent basis. The purpose
      of this research was to obtain a better understanding of the transitional phase
      to the first position as NP after graduation. The perceptions of preparation,
      gains, losses, barriers, facilitators, and strategies for adjustment were
      explored. A qualitative approach using focus groups was developed in which 21
      recent NP graduates from a large university participated in one of four focus
      groups. Peer debriefing and participant verification were techniques used to
      ensure credibility and trustworthiness of the data and subsequent analysis. The
      themes identified were: loss of personal control of time and privacy; changes and
      losses in relationships; feelings of isolation and uncertainty in establishing
      the NP role; and a special bonding with clients. Although the participants
      perceived they were adequately prepared for their role, they also described
      feelings of guilt and uncertainty from not knowing information they believed they
      should know. They concluded that they functioned differently than the physician
      as well as other nurses and found it necessary to distance themselves from the
      role of other health care providers. This study has implications for colleagues,
      academic institutions, and the individual nurse practitioner.

PMID- 11324833
TI  - Nurse practitioner preferences for distance education methods related to learning
      style, course content, and achievement.
AB  - The relationships among multiple distance delivery methods, preferred learning
      style, content, and achievement was sought for primary care nurse practitioner
      students. A researcher-designed questionnaire was completed by 86 (71%)
      participants, while 6 engaged in follow-up interviews. The results of the study
      included: participants preferred learning by "considering the big picture";
      "setting own learning plans"; and "focusing on concrete examples." Several
      positive associations were found: learning on own with learning by reading, and
      setting own learning plans; small group with learning through discussion; large
      group with learning new things through hearing and with having learning plans set
      by others. The most preferred method was print-based material and the least
      preferred method was audio tape. The most suited method for content included
      video teleconferencing for counseling, political action, and transcultural
      issues; and video tape for physical assessment. Convenience, self-direction, and
      timing of learning were more important than delivery method or learning style.
      Preferred order of learning was reading, discussing, observing, doing, and
      reflecting. Recommended considerations when designing distance courses include a
      mix of delivery methods, specific content, outcomes, learner characteristics, and
      state of technology.

PMID- 11324834
TI  - Research utilization: a challenge for nursing graduate education to improve
      patient care.
AB  - To improve patient care, hospitals and other health care facilities are looking
      to improve patient outcomes through examining how nursing care can be changed or
      modified based on research. The process of applying research results into
      clinical practice is called research utilization (RU). In this article, a
      master's level research utilization course is described. The process of research
      utilization is highlighted along with specifics regarding course development and
      evaluation methods. Graduate level research courses such as this one can assist
      students to demonstrate competency in research utilization including: synthesis
      of research literature, development of practice guidelines based on research, and
      identification of strategies to carry out RU protocols and evaluate outcomes.

PMID- 11324835
TI  - An experimental method for teaching research to graduate nursing students.
AB  - This article provides a creative and interactive method for teaching a
      metaparadigm of inquiry that values and embraces both naturalistic and
      positivistic approaches to research. The author outlines an experiential method
      for teaching graduate level research that blends opportunities to meet the needs
      of students with either global or analytic information processing styles, as well
      as varying student learning styles. The method involves a semester-long journey
      whereby students cognitively and viscerally begin to understand the
      interconnectedness of all research knowledge, and consists of five elements: 1)
      creating a nonthreatening environment; 2) using guided imagery; 3) teaching
      research along the "Continuum of Inquiry"; 4) take-home and midterm exams based
      on hypothetical clinical situations; and (5) developing a written research
      proposal.

PMID- 11324836
TI  - The child with a chronic condition: parents teach advanced practice nursing
      students.

PMID- 11324837
TI  - Using student-collected practice data as a teaching tool.
AB  - Research is an intimidating prospect for many students. This brief and fairly
      simple foray into data collection and analysis did not convince all students to
      embrace research. It did, however, entice many to consider how to incorporate
      data collection into their own beginning practices. Students who had stated their
      aversion to research found themselves arguing for the necessity of data
      collection to provide evidence for practice changes. There were also students who
      found the experience yet another busywork paper trail invented by the faculty.
      They resented the time and effort required for completion of another form during
      their busy clinical experiences. Other students remained adamantly opposed to
      considering any changes in what they saw as "appropriate" practice despite
      evidence to the contrary. An ongoing goal of education is to facilitate lifelong
      learning and investigation into clinical questions. The faculty plan to survey
      the graduates to ascertain what data collection efforts, if any, they are
      currently using. The educational program described in this project closed in
      December 1998 because of funding restrictions. One of the faculty in this project
      (Carr) and current colleagues are continuing to use the NMCDS to encourage
      students to examine and analyze their own practices. An additional use of the
      data set is for student-initiated research projects that focus on specific
      clinical questions. One faculty member was part of an effort to institute a
      similar project in a master's-based nurse-midwifery education program. That
      database has currently provided data for two master's degree projects. The uses
      of the NMCDS are not limited to graduate students or advanced practice
      clinicians. The tool is being used in an undergraduate maternity nursing clinical
      course to assist students in seeing differences in practice and the possible
      reasons for those differences. The Division of Research of the ACNM has sponsored
      the development of similar data collection tools for both ambulatory prenatal and
      well-woman care. The wellwoman tool is currently in the pilot stage (1999), and
      will be refined and further tested this year. The use of these data collection
      tools by advanced practice nurses would provide a wealth of data for both policy
      setting and clinical research. Educational programs frequently combine coursework
      for various advanced practice nursing pathways, and nurse-midwifery and nurse
      practitioner students would benefit from jointly focusing on practice patterns
      and participating in the analysis of student-collected data. The standardized
      tools for intrapartum, well-woman care, and antepartum care will be available to
      all of the 50 ACNM education programs as well as to practicing clinicians.

PMID- 11324838
TI  - Connecting classroom, clinic, and community: pediatric nurse practitioner student
      and faculty assessment of clinical experience at faculty practice sites.

PMID- 11324839
TI  - Human auditory steady-state responses to tones independently modulated in both
      frequency and amplitude.
AB  - OBJECTIVE: Independent amplitude and frequency modulation (IAFM) of a carrier
      tone uses two different modulating frequencies, one for amplitude modulation (AM)
      and one for frequency modulation (FM). This study measured the human steady-state
      responses to multiple IAFM tones. The first question was whether the IAFM
      responses could be recorded without attenuation of the AM and FM components. The
      second question was whether IAFM stimuli would provide a more effective
      demonstration of responses at intensities near threshold than the responses to AM
      tones. The third question was whether the responses to multiple IAFM stimuli
      would relate to the discrimination of words at different intensities. DESIGN:
      Multiple AM, FM, or IAFM stimuli were presented simultaneously. Responses were
      recorded between the vertex and the neck and analysed in the frequency domain.
      The first experiment compared IAFM responses with AM and FM responses. The second
      experiment compared IAFM responses with AM responses between intensities 20 to 50
      dB SPL. The third experiment related the IAFM responses to the discrimination of
      monosyllabic words at intensities between 20 and 70 dB SPL. RESULTS: Steady-state
      responses to the individual component of the IAFM stimuli were clearly
      recognizable although attenuated a little (14%) from the responses to AM or FM
      alone. Using IAFM stimuli was not different than simply using AM stimuli when
      trying to recognize responses at low intensities. The number of responses
      detected during multiple IAFM stimulation and the amplitudes of these responses
      correlated significantly with word discrimination. CONCLUSIONS: IAFM of a carrier
      using two different modulating frequencies (one for AM and one for FM) elicits
      separate AM and FM responses that are relatively independent of each other. These
      separate responses can be used to detect whether a particular carrier has been
      processed in the cochlea, but they are not as effective as measuring responses to
      carriers that have been modulated in both amplitude and frequency at the same
      modulation frequency (mixed modulation). The detectability of eight different
      responses (four AM and four FM) to an IAFM stimuli relates well to the ability of
      subjects to discriminate words. IAFM stimuli therefore show promise as an
      objective test for assessing suprathreshold hearing.

PMID- 11324840
TI  - The contribution of amplitude envelope cues to sentence identification in young
      and aged listeners.
AB  - OBJECTIVE: The purpose of this study was to examine the importance of amplitude
      envelope cues to sentence identification for aged listeners. We also examined the
      effect of increasing alterations (i.e., compression ratio) and amount of
      available frequency content (i.e., number of channels) for this population.
      DESIGN: Thirty-six listeners were classified according to their age (35 or
      younger versus 65 and older) and hearing status (normal hearing versus hearing
      impaired). Within each hearing status, mean hearing threshold thresholds for the
      young and aged listeners were matched as closely as possible through 4 kHz to
      control for sensitivity differences across age, and all listeners passed a
      cognitive screening battery. Accuracy of synthetic sentence identification was
      measured using stimuli processed to restrict spectral information. Performance
      was measured as a function of age, hearing status, amount of spectral
      information, and degradation of the amplitude envelope (using fast-acting
      compression with compression ratios ranging from 1:1 to 5:1). RESULTS: Mean
      identification scores decreased significantly with increasing age, the presence
      of hear- c ing loss, the removal of spectral information, and with increasing
      distortion of the amplitude envelope (i.e., higher compression ratios). There was
      a consistent performance gap between young and aged listeners, regardless of the
      magnitude of change to the amplitude envelope. This suggests that some cue other
      than amplitude envelope variations is inaccessible to the aged listeners.
      CONCLUSIONS: Although aged listeners performed more poorly overall, they did not
      show greater susceptibility to alterations in amplitude-envelope cues, such as
      those produced by fast-acting amplitude compression systems. It is therefore
      unlikely that compression parameters such as attack and release time or
      compression ratio would need to be a differentially programmed for aged
      listeners. Instead, the data suggest two possibilities: aged listeners have
      difficulty accessing the fine-structure temporal cues present in speech, and/or
      performance is degraded by age-related loss of function at a central processing
      level.

PMID- 11324841
TI  - Cognitive effects in dichotic speech testing in elderly persons.
AB  - OBJECTIVE: To study the effect of chronologic age on central auditory functions
      using dichotic speech tests and to study whether and how the age effect in
      dichotic listening is related to cognitive ability. DESIGN: Dichotic speech tests
      and cognitive tests were performed on 30 bilaterally hearing-impaired subjects,
      with a pure-tone average better than 50 dB HL. They were between 42 and 84 yr of
      age and were divided into an older and a younger group comprising 15 subjects
      each. The dichotic test material were digits, low-redundancy sentences and
      consonant-vowel syllables. The subjects reported stimuli heard in both ears (free
      report) or in one ear (directed report to left or right ear). The cognitive test
      battery comprised tests focusing on short-term memory, verbal information
      processing speed and phonologic processing. RESULTS: A decreased overall
      performance in all dichotic speech tests was observed in the older group. In the
      syllable test the older subjects showed poorer results when focusing on the
      stimuli heard in the left ear, as compared with when focusing on stimuli heard in
      the right ear, whereas the younger group showed almost equal results for left-
      and right ear-focusing conditions. An age effect was also seen in reaction times
      recorded in the cognitive tests and in the scores of the reading span test. These
      cognitive parameters correlate with the results of the dichotic test when
      focusing to the left, but not when focusing to the right in the directed report
      condition. In the free report condition the overall performance showed a high
      correlation with cognitive test parameters. CONCLUSIONS: Effects of chronologic
      age in dichotic speech tests in the elderly have been verified. The degree of
      effect is dependent on test material, way of reporting and focusing condition.
      The different listening tasks in dichotic tests put different demands on
      cognitive ability shown by a varying degree of correlations between cognitive
      function and dichotic test parameters. Also, the results indicate a strong
      connection between age-related cognitive decline in the elderly and problems to
      perceive stimuli presented to the left ear.

PMID- 11324842
TI  - Fitting low ratio compression to people with severe and profound hearing losses.
AB  - OBJECTIVE: In this study, we aimed to determine the extent to which wide dynamic
      range compression and compression limiting could benefit severely and profoundly
      hearing-impaired adults. DESIGN: Subjects were fitted with multi-memory hearing
      aids incorporating frequency independent input-controlled compression with a 2:1
      compression ratio and output-controlled compression limiting. The input
      compression threshold (CT) was varied to establish the lowest level that
      maintained audibility for conversational intensity speech without acoustic
      feedback oscillation. Where a low (40 to 57 dB SPL) CT was possible, this was
      compared with a moderate (65 to 74 dB SPL) level. The preferred input compression
      setting was subsequently compared with linear, compression-limited amplification
      in the same aids. In the three cases where 2:1 input compression could not be
      used, because of feedback or loudness insufficiency problems, compression
      limiting was compared with peak clipping. Field trials were conducted over a 2-
      or 3-mo period to establish preferences. RESULTS: Nine of the 16 subjects
      preferred the inclusion of the higher level input compression, and one preferred
      lower level input compression. Four subjects preferred linear, compression
      limited amplification, one favored peak clipping, and one could not be satisfied
      with any of the options provided. CONCLUSIONS: 2:1 input compression was useful,
      and preferred by 10 of the subjects, but for nine subjects the preferred CT was
      relatively high. With a group 4-frequency average loss of 87 dB HTL, the results
      demonstrate that fast-acting, low compression ratio systems can be useful for
      losses traditionally regarded as the domain of linear amplification.

PMID- 11324843
TI  - Using conjoint analysis to examine the importance of hearing aid attributes.
AB  - OBJECTIVE: To introduce conjoint analysis (CA) as a method to explain choice
      decisions of hearing aid users and to measure the contributions of different
      hearing aid attributes involved. DESIGN: The study was conducted using CA, a
      method that is well established in marketing, but has not been used for hearing
      aid research. CA examines the contributions (importance) various attributes make
      to overall preference judgements. It is based on the premises that objects (i.e.,
      hearing aids) can be described as different combinations of several attributes.
      The relative importance of the attributes is estimated from integral judgements
      of hypothetical hearing aids. The advantages of CA are a more realistic
      presentation of complete products instead of isolated attributes and the
      consideration of trade-offs between the features. The following attributes
      selected from 12 features in a prestudy were included in the application: speech
      perception in quiet, speech perception in noise, handling, sound quality,
      localization, and feedback. 93 randomly chosen experienced hearing aid wearers
      participated in the survey. RESULTS: It was found that the attributes concerning
      speech perception were by far most important. Speech discrimination in quiet and
      in noise were almost equally significant and contributed with 56% to the
      preference decisions of the subjects. The remaining attributes showed values in
      the range of 10% to 12%. When comparing various subgroups dependent on age, sex,
      hearing loss, satisfaction, etc., significant differences concerning the
      preferences were found. Elder and female subjects attached greater importance of
      the attribute "handling" whereas younger patients judged "speech in noise" more
      important. In general, subjects with greater hearing loss considered speech
      intelligibility in quiet to be more important than in noisy surroundings.
      Moreover, sound quality seems to be a significant indicator for satisfaction with
      the hearing aid. CONCLUSIONS: This study proposes CA as a survey technique to
      examine individual preferences for hearing aids. Several assumptions about the
      importance of hearing aid features for different groups of users could be
      confirmed quantitatively. Segmentation showed valid results depending on socio
      demographic and user-specific parameters. The method used and the results are of
      interest for audiologists as well as the hearing aid industry. They provide
      valuable tools for future hearing aid design and should be considered in the
      development of self-assessment inventories.

PMID- 11324844
TI  - Validation of the SADL questionnaire.
AB  - OBJECTIVE: To cross-validate the psychometric characteristics of the Satisfaction
      with Amplification in Daily Life (SADL) questionnaire (Cox & Alexander, 1999),
      and to explore the SADL's construct validity. DESIGN: Thirteen private practice
      Audiology clinics each distributed SADL questionnaires, by mail, to 20 adults who
      had recently obtained hearing aids. The completed questionnaires were returned to
      a central site and subject anonymity was assured. There were 196 usable
      responses. RESULTS: Psychometric characteristics of the items were found to be
      very similar to those reported previously. Thus, the internal validity of the
      instrument was strongly supported. The assumption that the SADL quantifies
      satisfaction by assessing its components was evaluated by examining the
      relationship between SADL scores and scores on a traditional single-item
      satisfaction measure. A logical and statistically significant relationship was
      seen between the two measures, thereby supporting the construct validity of both
      types of data. For private-pay clients, satisfaction scores were very similar to
      the interim norms published by Cox and Alexander (1999). However, clients whose
      hearing aids were partly or fully purchased by insurance or benefits programs
      tended to be more satisfied than interim norms for third-party pay clients
      derived 5 yr ago. For most types of clients, there was a tendency toward more
      satisfaction in the Negative Features subscale than observed in our previous
      research. CONCLUSIONS: Both construct and internal validity of the SADL
      questionnaire were supported by this research. The previously published interim
      norms appear to be mostly appropriate for private-pay clients, but might require
      adjustment in the Negative Features subscale. Further research is needed to
      explore the relationship between satisfaction and device purchase issues (third
      party versus private pay).

PMID- 11324845
TI  - High-frequency (8 to 16 kHz) reference thresholds and intrasubject threshold
      variability relative to ototoxicity criteria using a Sennheiser HDA 200 earphone.
AB  - OBJECTIVE: The first purpose of this study was to determine high-frequency (8 to
      16 kHz) thresholds for standardizing reference equivalent threshold sound
      pressure levels (RETSPLs) for a Sennheiser HDA 200 earphone. The second and
      perhaps more important purpose of this study was to determine whether repeated
      high-frequency thresholds using a Sennheiser HDA 200 earphone had a lower
      intrasubject threshold variability than the ASHA 1994 significant threshold shift
      criteria for ototoxicity. DESIGN: High-frequency thresholds (8 to 16 kHz) were
      obtained for 100 (50 male, 50 female) normally hearing (0.25 to 8 kHz) young
      adults (mean age of 21.2 yr) in four separate test sessions using a Sennheiser
      HDA 200 earphone. RESULTS: The mean and median high-frequency thresholds were
      similar for each test session and increased as frequency increased. At each
      frequency, the high-frequency thresholds were not significantly (p > 0.05)
      different for gender, test ear, or test session. The median thresholds at each
      frequency were similar to the 1998 interim ISO RETSPLs; however, large standard
      deviations and wide threshold distributions indicated very high intersubject
      threshold variability, especially at 14 and 16 kHz. Threshold repeatability was
      determined by finding the threshold differences between each possible test
      session comparison (N = 6). About 98% of all of the threshold differences were
      within a clinically acceptable range of +/-10 dB from 8 to 14 kHz. The threshold
      differences between each subject's second, third, and fourth minus their first
      test session were also found to determine whether intrasubject threshold
      variability was less than the ASHA 1994 criteria for determining a significant
      threshold shift due to ototoxicity. The results indicated a false-positive rate
      of 0% for a threshold shift > or = 20 dB at any frequency and a false-positive
      rate of 2% for a threshold shift >10 dB at two consecutive frequencies.
      CONCLUSIONS: This study verified that the output of high-frequency audiometers at
      0 dB HL using Sennheiser HDA 200 earphones should equal the 1998 interim ISO
      RETSPLs from 8 to 16 kHz. Further, because the differences between repeated
      thresholds were well within +/-10 dB and had an extremely low false-positive rate
      in reference to the ASHA 1994 criteria for a significant threshold shift due to
      ototoxicity, a Sennheiser HDA 200 earphone can be used for serial monitoring to
      determine whether significant high-frequency threshold shifts have occurred for
      patients receiving potentially ototoxic drug therapy.

PMID- 11324846
TI  - Central auditory plasticity: changes in the N1-P2 complex after speech-sound
      training.
AB  - OBJECTIVE: To determine whether the N1-P2 complex reflects training-induced
      changes in neural activity associated with improved voice-onset-time (VOT)
      perception. DESIGN: Auditory cortical evoked potentials N1 and P2 were obtained
      from 10 normal-hearing young adults in response to two synthetic speech variants
      of the syllable /ba/. Using a repeated measures design, subjects were tested
      before and after training both behaviorally and neurophysiologically to determine
      whether there were training-related changes. In between pre- and post-testing
      sessions, subjects were trained to distinguish the -20 and -10 msec VOT /ba/
      syllables as being different from each other. Two stimulus presentation rates
      were used during electrophysiologic testing (390 msec and 910 msec interstimulus
      interval). RESULTS: Before training, subjects perceived both the -20 msec and -10
      msec VOT stimuli as /ba/. Through training, subjects learned to identify the -20
      msec VOT stimulus as "mba" and -10 msec VOT stimulus as "ba." As subjects learned
      to correctly identify the difference between the -20 msec and -10 msec VOT
      syllabi, an increase in N1-P2 peak-to-peak amplitude was observed. The effects of
      training were most obvious at the slower stimulus presentation rate. CONCLUSIONS:
      As perception improved, N1-P2 amplitude increased. These changes in waveform
      morphology are thought to reflect increases in neural synchrony as well as
      strengthened neural connections associated with improved speech perception. These
      findings suggest that the N1-P2 complex may have clinical applications as an
      objective physiologic correlate of speech-sound representation associated with
      speech-sound training.

PMID- 11324847
TI  - Cochlear receptor (microphonic and summating potentials, otoacoustic emissions)
      and auditory pathway (auditory brain stem potentials) activity in auditory
      neuropathy.
AB  - OBJECTIVE: To define both auditory nerve and cochlear receptor functions in
      subjects with auditory neuropathy (AN). DESIGN: We tested 33 AN subjects (66
      ears) and compared them with 21 healthy subjects (28 ears). In AN subjects, the
      average pure-tone (1, 2, and 4 kHz) threshold loss was 57 dB HL. Click stimuli
      were used to elicit transient evoked otoacoustic emissions (TEOAEs), cochlear
      microphonics (CMs), and auditory brain stem responses (ABRs). Both cochlear and
      ABR potentials were recorded from surface electrodes (vertex-ipsilateral mastoid)
      using averaging procedures. The amplitudes and latencies of CMs and ABRs and the
      amplitude of the TEOAEs were analyzed. RESULTS: CM amplitudes recorded from
      normal ears decreased as a function of subject age. CMs recorded from AN subjects
      fell within the normal age-adjusted range in 60% of the subjects and were >2 SEEs
      (standard error of estimate) above the age-adjusted normal regression in 40% of
      the subjects. TEOAEs were absent in 19 (30%) AN ears (bilaterally in eight, and
      unilaterally in three subjects) and were present in 44 ears. In AN subjects,
      correlations among CM amplitude, TEOAE amplitude, and pure-tone average
      thresholds were not significantly related. CM amplitudes were not significantly
      different whether TEOAEs or ABRs were present or absent. The ABR was present in
      21% of AN subjects and consisted of a low-amplitude Wave V without a preceding
      Wave I. Measures of CM amplitude and PTA hearing loss were not significantly
      different in those AN ears with a preserved ABR compared with ears with absent
      ABRs. Summating potentials to transient click stimuli were of small amplitude
      (<0.1 microV) and detectable in approximately 50% of the AN and healthy control
      subjects limiting formal analysis of summating potentials. CONCLUSIONS: In a
      significant proportion of AN subjects, we found abnormalities of cochlear
      receptor function, including elevated CM amplitudes and absence of TEOAEs. These
      two abnormalities occurred independently of each other. A low amplitude Wave V of
      the ABR was found in approximately one-fifth of AN subjects, evidence that neural
      synchrony can be partially preserved in some subjects with this disorder.

PMID- 11324848
TI  - Medication schemas and memory for automated telephone messages.
AB  - The present study investigated whether older and younger adults use a schema to
      organize and remember spoken reminder messages for taking medication. Previous
      research has shown that older and younger adults share preferences for organizing
      printed instructions for taking medication, suggesting a shared schema. Older and
      younger participants in Experiment 1 of the present study used a similar schema
      to organize medication reminder messages. This finding suggests that the
      medication schema generalizes across communication purpose (to remind or to
      instruct) as well as across patient age. Medication reminder messages were better
      understood and remembered when organized to match this schema, whether the
      reminders were presented as automated telephone messages (Experiment 2) or in
      printed form (Experiment 3). Schema-compatible organization especially helped
      people draw inferences from the messages, suggesting that organization helps
      older and younger adults construct a situation model of the medication-taking
      task from the messages. Potential applications of organized messages include
      increasing the impact of automated systems for delivering health services.

PMID- 11324849
TI  - Effects of vehicle interior geometry and anthropometric variables on automobile
      driving posture.
AB  - The effects of vehicle package, seat, and anthropometric variables on posture
      were studied in a laboratory vehicle mockup. Participants (68 men and women)
      selected their preferred driving postures in 18 combinations of seat height, fore
      aft steering wheel position, and seat cushion angle. Two seats differing in
      stiffness and seat back contour were used in testing. Driving postures were
      recorded using a sonic digitizer to measure the 3D locations of body landmarks.
      All test variables had significant independent effects on driving posture.
      Drivers were found to adapt to changes in the vehicle geometry primarily by
      changes in limb posture, whereas torso posture remained relatively constant.
      Stature accounts for most of the anthropometrically related variability in
      driving posture, and gender differences appear to be explained by body size
      variation. Large intersubject differences in torso posture, which are fairly
      stable across different seat and package conditions, are not closely related to
      standard anthropometric measures. The findings can be used to predict the effects
      of changes in vehicle and seat design on driving postures for populations with a
      wide range of anthropometric characteristics.

PMID- 11324850
TI  - The effect of handle angle on MAWL, wrist posture, RPE, and heart rate.
AB  - In manual material handling tasks, the handle serves as the interface between the
      human operator and the box (the materials). Handle angle design can affect both
      wrist posture and lifting ability. This study was designed to evaluate the effect
      of handle angle on maximal acceptable weight of lifting (MAWL), perceived whole
      body exertion, whole-body workload, wrist posture, and perceived wrist exertion.
      The results indicate that handle angle had a significant effect on wrist posture
      and wrist rating of perceived exertion (RPE). A box with a 0 degrees handle angle
      induced the greatest ulnar deviation and the highest wrist RPE. A 75 degrees
      handle angle induced the greatest radial deviation and a relatively high wrist
      RPE. A 30 degrees handle angle resulted in the greatest MAWL and the lowest level
      of wrist RPE. Overall, these findings suggest that 30 degrees and 45 degrees
      handle angles can provide favorable coupling conditions for the cutout-type
      handhold container handle. Actual or practical applications include the ergonomic
      design of container handles for manual material handling tasks industry.

PMID- 11324851
TI  - A componential model of human interaction with graphs: VI. Cognitive engineering
      of pie graphs.
AB  - This paper proposes and tests the following three-component model of reading a
      pie graph to estimate segment size: (a) selecting a mentally represented anchor
      segment (25%, 50%, or 75%), (b) mentally aligning representations of the anchor
      and target segments, and (c) mentally adjusting the size of the anchor to match
      the target. Experiment 1 showed that the size difference between the target and
      closest anchor and the angular displacement of the target from vertical predicted
      response times (RTs) and absolute error. Experiment 2 demonstrated that an
      aligned pie graph, designed to reduce the "align" portion of the process,
      produced faster RTs and lower error than did a regular pie graph. Experiment 3
      showed that a pie graph labeled at the anchor values produced the same response
      times and absolute error as a regular pie graph but that a pie labeled off the
      anchor points produced a very different pattern of results. The discussion
      relates the results to the componential model and describes applications in
      increasing pie graph usability and developing design guidelines. Actual or
      potential applications of this research include guidelines for graph design and
      more usable pie graphs.

PMID- 11324853
TI  - Applying quality control charts to the analysis of single-subject data sequences.
AB  - Techniques from the field of quality control can be used to classify the quality
      of individual samples of physical or cognitive performance. After stable
      baselines have been established for an individual, deviations in performance can
      be evaluated using control charts. The effectiveness of this approach in
      evaluating cognitive performance was tested using databases collected under a
      variety of risk factors. The sensitivity and specificity characteristics of
      Shewhart, cumulative-sum (CUSUM), and exponentially weighted moving average
      (EWMA) control charts were determined for a total of 174 trials involving 10
      participants and 23 cognitive performance assessment measures. The most effective
      technique in each case was typically a function of the specific performance
      measure and the type of performance change being evaluated. Sensitivity and
      specificity for the best techniques were as high as 100%. This study demonstrated
      the usefulness of quality control charts as a tool to evaluate individual
      participant performance over time. Actual or potential applications of this
      research include readiness-to-perform screening of industrial workers in order to
      improve the health and safety of the workforce.

PMID- 11324852
TI  - Multiple two-dimensional displays as an alternative to three-dimensional displays
      in telerobotic tasks.
AB  - In this study a multiple-view two-dimensional (2D) display was compared with a
      three-dimensional (3D) monocular display and a 3D stereoscopic display using a
      simulated telerobotic task. As visual aids, three new types of visual enhancement
      cues were provided and evaluated for each display type. The results showed that
      the multiple-view 2D display was superior to the 3D monocular and the 3D
      stereoscopic display in the absence of the visual enhancement depth cues. When
      participants were provided with the proposed visual enhancement cues, the
      stereoscopic and monocular displays became equivalent to the multiple-view 2D
      display. Actual or potential applications of this study include the design of
      visual displays for teleoperation systems.

PMID- 11324854
TI  - Adaptation and sensitivity to postural change in sitting.
AB  - We used 3 psychophysics methods to determine perceptible changes in seat height,
      seat pan angle, and backrest angle using an experimental chair. In the method of
      adjustment, the chosen chair settings were affected by the initial setting. For
      example, a high initial setting of the seat height led to a high selected setting
      and a low setting led to a low value. The difference between settings was
      referred to as not noticeable difference (NND). The method of limits was used to
      determine acceptable chair settings using verbal limits such as "too high" and
      "too low." Using the method of constant stimuli, just noticeable differences
      (JNDs) were determined for chair height (1.5 cm), seat pan angle (1.2 degrees)
      and backrest angle (1.7 degrees). The corresponding values for NNDs and verbal
      limits were about twice as large: chair height (2.5 cm), seat pan angle (4
      degrees) and backrest angle (3 degrees). NNDs and verbal limits are unobtrusive
      measures that are considered more valid than JNDs, which exaggerate the need for
      adjustability. The results have practical implications for the design of office
      chairs.

PMID- 11324855
TI  - Visual search for grouped versus ungrouped icons in a computer interface.
AB  - The paradigm of visual search was used to investigate how participants looked for
      a target file among distracter files in an icon-based computer interface. The
      purpose of these experiments was to study the effect of icons and spatial
      grouping on scanning speed. Does spatial grouping of identical icons increase the
      scanning speed? Do icons themselves speed up the search for a target file when
      compared with a condition in which the files are indicated with mere textual
      labels? Our results showed that both the presence of icons and their grouping had
      a significant positive effect on the scanning speed. Potential applications of
      this research include the design of graphics-based interfaces, such as the
      effective arrangement of icons in an interface.

PMID- 11324856
TI  - Fuzzy signal detection theory: basic postulates and formulas for analyzing human
      and machine performance.
AB  - Signal detection theory (SDT) assumes a division of objective truths or "states
      of the world" into the nonoverlapping categories of signal and noise. The
      definition of a signal in many real settings, however, varies with context and
      over time. In the terminology of fuzzy logic, a real-world signal has a value
      that falls in a range between unequivocal presence and unequivocal absence. The
      definition of a response can also be nonbinary. Accordingly the methods of fuzzy
      logic can be combined with SDT, yielding fuzzy SDT. We describe the basic
      postulates of fuzzy SDT and provide formulas for fuzzy analysis of detection
      performance, based on four steps: (a) selection of mapping functions for signal
      and response; (b) use of mixed-implication functions to assign degrees of
      membership in hits, false alarms, misses, and correct rejections; (c) computation
      of fuzzy hit, false alarm, miss, and correct rejection rates; and (d) computation
      of fuzzy sensitivity and bias measures. Fuzzy SDT can considerably extend the
      range and utility of SDT by handling the contextual and temporal variability of
      most real-world signals. Actual or potential applications of fuzzy SDT include
      evaluation of the performance of human, machine, and human-machine detectors in
      real systems.

PMID- 11324857
TI  - Frames of reference for the display of battlefield information: judgment-display
      dependencies.
AB  - In 2 experiments, U.S. Army soldiers viewed computer-generated displays that
      presented battlefield information from 3 different frames of reference: a 2D plan
      view display (with contour lines), a 3D exocentric perspective display, and an
      interactive 3D immersed display. In Experiment 1, soldiers made geographical
      judgments. The results suggested that both 3D displays suffered from ambiguity of
      distance estimates but that the 3D immersed display was most accurate for judging
      whether a location is directly visible from another. In Experiment 2, the 3D
      exocentric display was compared with a 3D immersed view, coupled with a small 2D
      inset map, in a more continuous battlefield scenario in which judgments of enemy
      activity were made. The findings of 3D ambiguity were replicated from Experiment
      1. The accuracy of judgments of enemy activity suffered with the immersed display
      when information necessary to answer correctly did not appear in the initial
      forward view and required panning to acquire, reflecting the cognitive demands of
      integration across different views. This display also hindered soldiers' ability
      to report changes in enemy activity from one scene to the next. The results of
      this research will help to provide guidelines for the appropriate choice of
      computer display technology to assist in designing battlefield visualization
      aids. Caution should be exercised in choosing immersive viewpoints.

PMID- 11324858
TI  - Vehicle and driver attributes affecting distance from the steering wheel in motor
      vehicles.
AB  - The current study was designed to confirm that female drivers sit closer to the
      steering wheel than do male drivers and to investigate whether this expected
      difference in sitting position is attributable to differences in the physical
      dimensions of men and women. Driver body dimensions and multiple measures of
      sitting distance from the steering wheel were collected from a sample of 150 men
      and 150 women. The results confirmed that on average, women sit closer to the
      steering wheel than men do and that this difference is accounted for by
      variations in body dimensions, especially height. This result suggests that
      driver height may provide a good surrogate for sitting distance from the steering
      wheel when investigating the role of driver position in real-world crash
      outcomes. The potential applications of this research include change to vehicle
      design that allows independent adjustment of the relative distance among the
      driver's seat, the steering wheel, and the floor pedals.

PMID- 11324859
TI  - Heterogeneity of semantic and visuospatial deficits in early Alzheimer's disease.
AB  - Staging of visuospatial and semantic deficits in patients with dementia of the
      Alzheimer type (DAT) was examined. The authors hypothesized that semantic ability
      would be more impaired in these patients, reflecting predominant temporal
      pathology early in the disease. However, in the 1st study (n = 26), 3 patients
      (11.5%) had marked visual but no semantic impairment. This finding was extended
      in a 2nd study with a 2nd patient sample (n = 21) and more specific tasks. Two
      patients (9.5%) again had visual but no semantic impairment. These studies
      confirm that, in patients with DAT presenting with relatively focal deficits,
      visual deficits sometimes occur before semantic problems. The findings are
      discussed with regard to the cognitive demands and neuroanatomical underpinning
      of the tests used and point to the necessity of using cognitively specific tests
      to enable accurate analysis of deficits in the context of the neuroanatomical
      basis of impairment.

PMID- 11324860
TI  - Sex differences favoring women in verbal but not in visuospatial episodic memory.
AB  - Sex differences favoring women have been found in a number of studies of episodic
      memory. This study examined sex differences in verbal, nonverbal, and
      visuospatial episodic memory tasks. Results showed that although women performed
      at a higher level on a composite verbal and nonverbal episodic memory score, men
      performed at a higher level on a composite score of episodic memory tasks
      requiring visuospatial processing. Thus, men can use their superior visuospatial
      abilities to excel in highly visuospatial episodic memory tasks, whereas women
      seem to excel in episodic memory tasks in which a verbalization of the material
      is possible.

PMID- 11324861
TI  - Material-specific memory in traumatic brain injury: differential effects during
      acquisition, recall, and retention.
AB  - Material-specific memory refers to the ability to learn and recall new episodic
      information on the basis of the nature of the stimulus material (e.g., verbal vs.
      nonverbal-visuospatial). Structural equation modeling was used to analyze data
      from a sample of patients with traumatic brain injury to compare 3 models of
      memory functioning: material-specific, material-specific plus general, and
      general (non-material-specific). The models were examined separately for
      acquisition, delayed free recall, and retention aspects of memory. Results
      suggest that, at least in a population with traumatic brain injury, the
      acquisition of new information takes place in a material-specific memory fashion,
      delayed free recall involves both material-specific and general (non-material
      specific) memory components, but retention relies primarily on general (non
      material-specific) memory processes.

PMID- 11324862
TI  - Attention processes in children with shunted hydrocephalus versus attention
      deficit-hyperactivity disorder.
AB  - Children with congenital hydrocephalus, children with attention deficit
      hyperactivity disorder, and normal controls were evaluated with measures of
      focused attention (Visual Orienting and Detection Task), sustained attention
      (continuous performance test), and attention shifting (Wisconsin Card Sorting
      Test). Components from these tasks have been linked to attention systems mediated
      by anterior or posterior brain networks. Children with congenital hydrocephalus
      showed an inability to focus and shift attention, which specifically implicated
      impairment of the disengage and move components of the posterior brain attention
      system. Children with attention deficit-hyperactivity disorder displayed the
      expected performance patterns on measures of focused attention once their
      difficulties with sustained attention were taken into account. However, they
      showed problems with shifting and sustaining attention, which are commonly
      associated with the anterior brain attention system.

PMID- 11324863
TI  - Effectiveness of attention rehabilitation after an acquired brain injury: a meta
      analysis.
AB  - The efficacy of attention rehabilitation after an acquired brain injury was
      examined meta-analytically. Thirty studies with a total of 359 participants met
      the authors' selection criteria. Studies were categorized according to whether
      training efficacy was evaluated by comparing pre- and posttraining scores only or
      included a control condition as well. Performance improved significantly (using
      the d+ statistic) after training in pre-post only studies but not in pre-post
      with control studies. Further analyses showed that specific-skills training
      significantly improved performance of tasks requiring attention but that the
      cognitive-retraining methods included in the meta-analysis did not significantly
      affect outcomes. These findings demonstrate that acquired deficits of attention
      are treatable using specific-skills training. Implications of these results for
      rehabilitation theory and future research are discussed.

PMID- 11324864
TI  - Executive functioning and olfactory identification in young adults with attention
      deficit-hyperactivity disorder.
AB  - Young adults with attention deficit-hyperactivity disorder (ADHD; N = 105) were
      compared with a control group (N = 64) on 14 measures of executive function and
      olfactory identification using a 2 (group) X 2 (sex) design. The ADHD group
      performed significantly worse on 11 measures. No Group X Sex interaction was
      found on any measures. No differences were found in the ADHD group as a function
      of ADHD subtype or comorbid oppositional defiant disorder. Comorbid depression
      influenced the results of only 1 test (Digit Symbol). After IQ was controlled
      for, some group differences in verbal working memory, attention, and odor
      identification were no longer significant, whereas those in inhibition,
      interference control, nonverbal working memory, and other facets of attention
      remained so. Executive function deficits found in childhood ADHD exist in young
      adults with ADHD and are largely not influenced by comorbidity but may be partly
      a function of low intelligence.

PMID- 11324865
TI  - Deficits in memory strategy use related to prefrontal dysfunction during early
      development: evidence from children with phenylketonuria.
AB  - The prefrontal cortex has been implicated in the mediation of executive processes
      that facilitate learning and memory. The authors hypothesized that children with
      prefrontal dysfunction related to phenylketonuria (PKU) would experience deficits
      in learning and memory because of impaired strategy use. They evaluated 23
      children with PKU and 23 controls by using the California Verbal Learning Test
      Children's Version (CVLT-C). General executive abilities were tested using the
      Stroop Color and Word Test, the Wisconsin Card Sorting Test, and phonemic and
      category fluency. Children with PKU, especially older children, showed poorer
      learning across trials and less use of semantic clustering on the CVLT-C but
      intact retention of previously encoded information. With the exception of
      phonemic fluency, deficits were not observed in general executive control.
      Results are discussed within the context of abnormalities in the prefrontal
      cortex and white matter of the brain.

PMID- 11324866
TI  - Perceptual false recognition in Alzheimer's disease.
AB  - Previous research has found that patients with probable Alzheimer's disease (AD)
      show lower levels of false recognition of semantic associates than do healthy
      older adults. To investigate whether this finding is attributable to semantic
      impairments in patients with AD, the authors examined false recognition of
      perceptually related novel objects with little semantic content in patients with
      AD and healthy older adults. By using corrected recognition scores to control for
      unrelated false alarms, it was found that patients with AD showed lower levels of
      both true and false recognition of novel objects than did older adults. These
      results suggest that the previous difference in false recognition of semantic
      associates observed between patients with AD and older adults is not entirely
      attributable to semantic memory deficits in patients with AD but may also involve
      poorly developed gist information in these patients.

PMID- 11324867
TI  - Latent inhibition with a response time measure from a within-subject design:
      effects of number of preexposures, masking task, context change, and delay.
AB  - Latent inhibition (LI), poorer performance on a learning task to a previously
      irrelevant stimulus than to a novel stimulus, was produced in 4 experiments,
      using a within-subject design and a response time (RT) measure. LI was reduced by
      decreasing the number of stimulus preexposures, omitting the masking task,
      changing the context from the preexposure to the test phase, and introducing a
      delay between the 2 phases. Together, these effects indicate that the within
      subject RT-based LI reflects the same processes as those that govern between
      subject LI with correct response as the dependent measure. The new procedure
      provides an advantageous method for assessing attentional dysfunction related to
      the processing of irrelevant stimuli, particularly in pathological groups, such
      as patients with schizophrenia.

PMID- 11324868
TI  - Semantic, phonological, and hybrid veridical and false memories in healthy older
      adults and in individuals with dementia of the Alzheimer type.
AB  - Five groups of participants (young, healthy old, healthy old-old, very mild
      dementia of the Alzheimer type [DAT], and mild DAT) studied 12-item lists of
      words that converged on a critical nonpresented word (cold) semantically (chill,
      frost, warm, ice), phonologically (code, told, fold, old), or in a hybrid list of
      both (chill, told, warm, old). The results indicate that (a) veridical recall
      decreased with age and dementia; (b) recall of the nonpresented items increased
      with age and remained fairly stable across dementia; and (c) false recall varied
      by list type, with hybrid lists producing superadditive effects. For hybrid
      lists, individuals with DAT were 3 times more likely to recall the critical
      nonpresented word than a studied word. When false memory was considered as a
      proportion of veridical memory, there was an increase in relative false memory as
      a function of age and dementia. Results are discussed in terms of age- and
      dementia-related changes in attention and memory.

PMID- 11324869
TI  - Recognizing identical versus similar categorically related common objects:
      further evidence for degraded gist representations in amnesia.
AB  - Studies have shown lower false recognition of semantically related lure words in
      patients with global amnesia than in matched controls. This pattern has been
      interpreted as suggesting that medial temporal and diencephalic structures that
      are damaged in amnesia and that contribute to veridical memory also contribute to
      false recognition. It has been argued that whereas controls form and retain a
      well-organized representation of the semantic gist of studied items, patients
      with amnesia can retain only a degraded gist representation. However, these
      studies are subject to an alternative interpretation involving greater source
      confusions in controls. The authors used a categorized-pictures paradigm to test
      recognition under conditions in which source confusions were unlikely to occur.
      Relative to controls, patients with amnesia showed reduced false recognition of
      categorically related pictorial lures, thereby supporting the notion of degraded
      gist representations in amnesia.

PMID- 11324870
TI  - Profile of cognitive functioning in women with the fragile X mutation.
AB  - Two studies tested the specificity of the neurocognitive profile of women with
      fragile X syndrome (FXS). First, women with an FXS full mutation were compared
      with women with a premutation and women without FXS who grew up in FXS families.
      Women with FXS had a significantly lower IQ than the other groups, and analyses
      of subtest profiles showed they had a relative weakness on Arithmetic and
      strength on Picture Completion. Women with FXS performed worse than the other
      groups on executive function, spatial ability, and visual memory. Next, women
      with FXS were compared with women without FXS matched on age and IQ. A similar IQ
      profile was found, but women with FXS were worse than controls only on executive
      function. The authors also examined which neurocognitive indices were related to
      the underlying biology of the disorder. Overall, the results indicated that
      executive rather than visuospatial deficits were primary in the neurocognitive
      profile of FXS.

PMID- 11324871
TI  - Joints of the cervical vertebral column.
AB  - The developing understanding of the morphology of the cervical spine has revealed
      the complexity of the system. A review of selected literature reported that a
      number of the joints have an unusual nature and exhibit complicated and even
      paradoxical motions. For the practicing therapist, the significance of these
      observations is that assessment and treatment procedures of the cervical spine
      must be very carefully analyzed. There are significant differing behaviors of
      some of the cervical joints in response to small changes in movement patterns or
      initial positioning. Therefore it is not possible to broadly classify results of
      assessment procedures as normal or pathological without a clear and detailed
      understanding of the underlying morphology.

PMID- 11324872
TI  - Cervical headache.
AB  - Headache presents a diagnostic challenge for the physical therapist due to
      similarities of signs and symptoms among the many types of headache. Effective
      treatment depends upon accurate diagnosis and identifying the factors that may
      precipitate or perpetuate the symptoms. This commentary overviews some common
      forms of headache and specifically addresses cervical headache as a possible
      beneficiary of physical therapy intervention. Details of the history and physical
      examination, which is designed to diagnose cervical headache and rule out
      potential serious pathologies, are presented. Guidelines for treatment of
      articular and myofascial dysfunction are presented. A case report illustrating
      principles of examination, inherent ambiguities in diagnosis, and successful
      treatment is also presented.

PMID- 11324873
TI  - Diagnosis and treatment of cervical spine clinical instability.

PMID- 11324874
TI  - Clinical outcome from mechanical intermittent cervical traction for the treatment
      of cervical radiculopathy: a case series.
AB  - STUDY DESIGN: Case series. OBJECTIVE: To describe the clinical outcomes of 15
      patients with cervical radiculopathy treated with mechanical intermittent
      cervical traction. BACKGROUND: Effectiveness of traction for the treatment of
      cervical spinal syndromes is controversial and the outcome of this treatment has
      not been established in the literature. METHODS AND MEASURES: Fifteen patients
      (45.5 +/- 13 years) completed a course of treatment using mechanical intermittent
      cervical traction. Eleven patients presented at baseline with radicular symptoms
      of 12 weeks duration or less, and 4 patients had long-standing radicular symptoms
      lasting more than 12 weeks. Outcome was measured using the Neck Disability Index
      (NDI) and the Numeric Pain Rating Scale (NPRS). RESULTS: Eight of the 15 cases
      (53%) in this series demonstrated complete pain resolution; these patients had
      symptom duration of 12 weeks and less. Seven of these 8 cases displayed a final
      NDI of 10% or less. Three out of 4 of the patients with symptom duration more
      [corrected] than 12 weeks showed no reduction in pain or increased pain rating,
      with minimal change in perceived disability of 12% or less. CONCLUSION: In this
      case series, patients with radicular symptoms lasting for 12 weeks and less
      demonstrated a reduction in pain and perceived disability. The NDI, when used in
      conjunction with the NPRS, provides a more comprehensive assessment of the
      patient with cervical radiculopathy, thus allowing the clinician to make a better
      judgment about the clinical effects of cervical traction.

PMID- 11324875
TI  - An outcomes analysis and satisfaction survey of 199 consecutive abdominoplasties.
AB  - Abdominoplasty is a popular body-contouring procedure. In this study the authors
      review retrospectively 199 abdominoplasty patients during a 15-year period to
      identify factors that affect overall outcome. Patients included 190 women and 9
      men. The complication rate was 32% with few major complications (1.4%). The
      revision rate was 43%, and was related to fine-tuning the aesthetic appearance.
      Patients were divided into four groups based on tobacco use and history of
      diabetes and hypertension. There was no significant difference in revision rates
      or major complications between the subgroups. Minor complication rates, however,
      were significantly higher in smokers and patients with diabetes and/or
      hypertension. Complication and revision rates in patients undergoing intra
      abdominal procedures combined with abdominoplasty were not significantly
      different from those patients undergoing abdominoplasty alone. A patient survey
      revealed symptom improvement in 95% of patients. Eighty-six percent of patients
      were satisfied with their result, and 86% would recommend abdominoplasty to a
      friend. The authors conclude that abdominoplasty is a safe and satisfying
      procedure, whether performed alone or in conjunction with another procedure.
      Patients are pleased with the outcome and have improvement in their symptoms,
      with minimal health risk. There is, however, a significant incidence of minor
      complications, related primarily to wound healing. These complications are
      increased significantly in smokers and patients with diabetes and/or
      hypertension. Revision rates are not different significantly between the
      subgroups. When complications do occur or revisions are required, they are minor
      and managed easily in an office setting.

PMID- 11324876
TI  - Oriental double eyelid: a limited-incision technique.
AB  - Although there are many procedures reported in the literature regarding the
      double-eyelid operation, they can be categorized basically into two groups:
      nonincision and incision. Conventionally, the nonincision technique has been
      shown to produce little postoperative edema. However, the probability of the fold
      disappearing is high, and this technique cannot be performed in patients with
      fatty eyelids. Conversely, the incision technique has contrary characteristics.
      As an alternative option, the author developed a limited-incision single-stitch
      technique that minimizes tissue injury and provides adequate adhesion for fold
      formation. With this method, a small single incision (3-4 mm) is made in the
      upper eyelid. Through the incision, the orbital fat can be removed, when
      indicated. Under direct vision, a levator aponeurosis or tarsus is attached to
      the muscle and the dermis of the pretarsal margin by a single stitch. This
      technique gives a durable, natural fold; has a short recovery time; and can be
      applied to patients with fatty eyelids. This method has the merits of both the
      incision and the nonincision techniques, and avoids the disadvantages of both
      procedures.

PMID- 11324877
TI  - Correction of the bilateral complete cleft lip: transformation to a unilateral
      incomplete cleft lip closure.
AB  - The complete lip alveolus and cleft palate is the most difficult of all bilateral
      clefts to treat because of the deformity of and tissue insufficiency in the
      prolabium. A bilateral concomitant procedure is impractical for treatment of this
      condition because of the problems that have to be resolved postoperatively,
      including a short columella, a lack of philtrum, labial horizontal and vertical
      insufficiency, and vermilion and alveolar vestibulum insufficiency. A two-stage
      procedure called the transformation method has been developed to circumvent these
      problems, and the authors present it here. With this method one side is closed
      completely using the maximum amount of tissue available. Concomitantly,
      incomplete closure is performed on the other side. The result at the end of the
      first stage of the procedure is a condition approximating unilateral incomplete
      closure. The results were obtained from 6 patients who underwent complete
      bilateral closure and were followed for at least 2 years with satisfactory
      results.

PMID- 11324878
TI  - Sciatic nerve reconstruction: limb preservation after sarcoma resection.
AB  - Limb salvage for extremity sarcoma has become the standard of care when possible.
      This review attempts to determine the outcome of sciatic nerve reconstruction
      after surgical tumor resection. The authors' objective was to determine the
      clinical value of extremity salvage with such a defect. Five patients (two male,
      three female) were selected from a department database at The University of Texas
      M.D. Anderson Cancer Center between 1995 and 1999 who met the following criteria:
      lower limb tumor resection involving a gap in the sciatic nerve with subsequent
      nerve autograft reconstruction. An additional patient who underwent primary
      sciatic nerve neurorrhaphy was also included. The average tumor size was 203 cm2.
      The most common tumor histology was spindle cell sarcoma. The average autograft
      length was 13 +/- 3.2 cm with one to four cables employed. Currently, 3 patients
      are still alive. Four of the 5 patients who received sciatic autonerve grafts
      reported partial distal sensory recovery subjectively. The patient who underwent
      primary neurorrhaphy has both motor and sensory innervation 42 months after
      surgery. Although not ideal for all patients, sciatic nerve reconstruction is a
      viable option for those willing to undergo limb preservation. Notable limitations
      to daily activity do not appear to be present, and patients are able to ambulate
      with or without assistive devices. With aggressive rehabilitation, some patients
      are able to function quite well with this bioprosthesis. Patients should
      consider, however, that their extremity is on loan. Substantial wound
      complications or infections may ultimately lead to amputation.

PMID- 11324879
TI  - A comparison between clinical results and electromyographic analysis after median
      or ulnar nerve injuries in children's wrists.
AB  - The purpose of this study was to analyze the results of median or ulnar nerve
      transections to the wrist in 14 children between 1994 and 1999. On sustaining
      their injury, all patients underwent treatment at the University Hospital of
      Nancy. They were all seen afterward for clinical and electromyographic
      evaluations. The clinical examination was mainly to judge the quality of sensory
      recovery, using the Weber and Dellon tests, as well as motor recovery.
      Electromyographic examination of the motor and sensory tissues was carried out
      systematically on each patient. The analysis of these results highlights
      discordance between the quality of the clinical results and nerve regrowth
      identified via electromyography. Good nerve regrowth does not necessarily mean a
      good sensory recovery.

PMID- 11324880
TI  - Mandibular contour reconstruction with three-dimensional computer-assisted
      models.
AB  - Facial contours are thought to depend on the appropriate balance of hard and soft
      tissue. To obtain aesthetically good results in head and neck reconstruction,
      surgeons should know the exact three-dimensional shape and volume of both hard
      and soft tissue to be reconstructed. The authors used computer-assisted three
      dimensional solid models of the mandible in 7 patients (4 women and 3 men) who
      underwent mandibular contour reconstruction. Scapular osteocutaneous flaps were
      used in all 7 patients. The follow-up periods ranged from 7 to 57 months (mean
      follow-up, 29 months). No flap was lost. One patient died of metastatic cancer.
      In 2 patients the aesthetic results were excellent and in 4 patients they were
      good. Computer-assisted three-dimensional models for mandibular contour
      reconstruction in head and neck reconstruction are quite useful.

PMID- 11324881
TI  - Pediatric melanoma: confirming the diagnosis with sentinel node biopsy.
AB  - Many pediatric melanoma lesions present at a more advanced stage than those in
      the adult population. Clinical and histological melanoma mimics, including a
      subset of Spitz nevi, are difficult to discriminate from melanoma. When dealing
      with a childhood melanoma, the clinician is likely to be faced with a thick
      lesion, and one in which the actual diagnosis may even be in doubt. There is a
      paucity of data to guide the physician in his management of melanoma in this age
      group, particularly with respect to node status and adjuvant therapy. The authors
      present two cases of pediatric melanoma in which the novel use of sentinel node
      biopsy helped confirm the diagnosis of melanoma, determined the need for full
      lymph node dissection, and guided the use of adjuvant interferon therapy.

PMID- 11324882
TI  - Endoscopic shaver with liposuction for treatment of axillary osmidrosis.
AB  - Axillary osmidrosis is a distressing problem, and in severe cases patients may
      seek a permanent solution. Many treatment techniques have been developed that
      involve destruction or removal of the apocrine and eccrine glands. Previous
      methods have been hampered by surgical or aesthetic concerns. From June 1999 to
      June 2000, 64 patients (43 women and 21 men) were treated surgically for axillary
      osmidrosis. A 1-cm incision is made in the axillary crease. An endoscopic shaver
      is inserted, extended to the edge of the axilla, and subcutaneous tissue and
      glands are excised as the shaver is drawn from the axillary edge to the crease.
      Suction connected to the shaver immediately removes excised tissue. This
      procedure is repeated throughout the entire axilla. Malodor elimination was good
      in 117 of 128 axillae (91.4%) treated, fair in 8 (6.3%), and poor in 3 (2.3%).
      The resulting scar is small and essentially invisible because it is located in
      the axillary crease. This technique results in a small, inconspicuous scar; a
      surgical time of only 40 minutes; patients resuming exercise and daily activities
      within 5 days of surgery; and high patient satisfaction.

PMID- 11324883
TI  - Evaluation of a combined calcium sodium alginate and bio-occlusive membrane
      dressing in the management of split-thickness skin graft donor sites.
AB  - The optimal treatment of the split-thickness skin graft (STSG) donor site remains
      an unresolved issue. This study was conducted to evaluate the combined use of
      calcium sodium alginate and a bio-occlusive membrane dressing in the management
      of STSG donor sites. This study was a prospective evaluation of all patients
      requiring an STSG over a 6-month period ending October 1998. There were 57
      patients with a mean age of 61 years. All skin grafts were harvested with an
      electric dermatome from the anterior thigh and were 0.012 to 0.016 inches thick.
      Donor sites were dressed with calcium sodium alginate followed by a bio-occlusive
      dressing. Postoperatively, the skin graft donor site dressing was removed and
      replaced. The mean skin graft area was 114 cm2. The first dressing change
      occurred, on average, 3 days postoperatively. All dressings were taken down and
      the wounds reevaluated 7 days postoperatively. Fifty-two patients (91%) had
      achieved complete reepithelialization by this time. Five patients (9%) required
      an additional dressing. All wounds were healed completely by postoperative day
      10. Donor site discomfort was minimal and limited to the time of dressing change.
      There were no wound-related complications. The average cost of dressing supplies
      was $48.00 per patient and $23.00 per dressing. This method of managing STSG
      donor sites allowed for unimpeded reepithelialization without wound complication.
      The bio-occlusive dressing eliminated the pain typically associated with fine
      mesh gauze dressings. The absorptive property of the calcium sodium alginate
      eliminated the problem of seroma formation and leakage seen routinely with the
      use of a bio-occlusive dressing alone. These results confirm that this technique
      is both efficacious and cost-effective.

PMID- 11324884
TI  - Which dressing for split-thickness skin graft donor sites?
AB  - There are a variety of methods used for the postoperative management of the donor
      site created after harvesting a split-thickness skin graft. The authors compare
      three major groups of dressings-open, semiopen, and closed-performed on 60
      patients divided into three groups. These different dressings were compared based
      on healing time, quality of the regenerated skin, and patient comfort. Biopsy
      specimens were obtained from the donor sites of each group for the assessment of
      healing quality and stage. An ideal donor site dressing method is one that
      affords protection from dehydration and prevention of wound and infection while
      also achieving rapid and painless healing of the donor site. The closed-dressing
      group had the shortest healing time, shown both clinically and histologically,
      and superior patient comfort was also documented in this group. The closed
      dressing group showed qualitatively superior healing when compared with open and
      semiopen donor sites. This was attributed to protection from dehydration and
      mechanical trauma, and avoidance of exogenous contamination.

PMID- 11324885
TI  - Mental development after modified pi procedure: dynamic cranioplasty for sagittal
      synostosis.
AB  - A prospective developmental assessment was performed on 26 patients operated on
      with dynamic cranioplasty for sagittal synostosis. Because this technique entails
      the application of compressive force, it was of great concern to assess the
      effect of surgery on development and mental status. The surgical technique used
      was a modified pi procedure. Perioperative variables were recorded. Six patients
      underwent preoperative intracranial pressure (ICP) measurements. To evaluate
      objectively the developmental outcome, the Griffiths' Mental Development Scales
      was used for analysis before and after surgery. A parental questionnaire was used
      for subjective outcome measurement. Preoperative ICP recordings during sleep
      ranged from 12.8 to 22.8 mmHg (mean, 16.1 mmHg). The mean age at the time for
      surgery was 6.9 months (range, 4-16 months; standard deviation [SD], 2.32
      months). The surgical technique included shortening of the anteroposterior
      diameter of the skull by a mean of 16.6 mm. The mean global development quotient
      (GDQ) preoperatively was 104.5 (range, 82-144; SD, 12.4) and the mean GDQ
      postoperatively was 101.4 (range, 62-129; SD, 13.6). Mean age at follow-up was
      16.3 months (range, 9-40 months; SD, 4.04 months). There was no significant
      correlation between the amount of intraoperative shortening and mental
      development. In comparison of means, the GDQ preoperatively did not differ
      significantly from the GDQ postoperatively. The modified pi procedure is safe and
      efficient. When surgery was performed before 1 year of age, no significant (p =
      0.33) effect on mental development-either detrimental or beneficial-was
      demonstrated.

PMID- 11324886
TI  - "Pac Man" flap for closure of pressure sores.
AB  - The purpose of this study was to modify the classic bilateral V-Y advancement
      flap procedure to decrease the tension in its closure and to break the midline
      vertical scar by interdigitating the flaps. After debridement of a pressure sore,
      the V-Y flaps were marked on both sides of the wound. Skin incisions were carried
      down to the muscle fascia along the sides of the flaps. The upper and lower limbs
      of the V-shaped flaps were elevated as triangular flaps but remained attached to
      the main flap. The tip of the upper limb of one of the flaps was transposed into
      the defect and sutured to the contralateral V-Y flap at the midpoint of its
      concave side facing the defect. The lower limb of the contralateral flap was then
      transposed into the defect and sutured to the first V-Y flap. To complete the
      interdigitated closure, the lower limb of the first flap was sutured below the
      contralateral flap, and the upper limb of the contralateral flap was sutured
      above the first flap. The final view of the flaps was similar to "Pac Man," so
      the authors decided to call this flap the Pac Man flap. The flaps healed well in
      all patients, and wound breakdown or recurrence of the pressure sore was not
      observed during the 3 to 14-month follow-up.

PMID- 11324887
TI  - Limited use of cyclosporin A in skeletal muscle ischemia--reperfusion injury.
AB  - Reperfusion injury is propagated by an inflammatory-mediated tissue edema and
      damage after reestablishment of vascular flow following an initial ischemic
      insult. In the field of transplantation, cyclosporin A(CsA) provides protection
      against chronic graft rejection through lymphocyte immunosuppression. Evidence
      for an independent protective effect of CsA against ischemia-reperfusion (IR)
      injury during organ transfer has prompted studies showing the benefit of CsA in
      various ischemia-exposed visceral organs. The authors hypothesized that CsA
      administration may similarly benefit IR injury after skeletal muscle amputations.
      To determine the effects of CsA on IR injury the authors induced 4 hours of
      ischemia on the gracilis muscle in a rat model. CsA (15 mg per kilogram orally)
      was administered in two experimental groups: (1) preischemic (N = 6): 48, 24, and
      3 hours before ischemia; and (2) postischemic (N = 6): 30 minutes after induction
      of ischemia. The effects of CsA on IR muscle injury were observed in each of the
      experimental groups as well as a control group (N = 6) exposed to similar
      ischemia and administered a saline vehicle. Muscle viability (nitro blue
      tetrazolium staining) and muscle edema (wet-to-dry weight ratio) were assessed 24
      hours after reperfusion. The preischemic CsA-treated gracilis muscle group
      demonstrated improved muscle viability (39.1 +/- 4.8%) when compared with the
      ischemic control muscle group (23.8 +/- 7.1%; p = 0.039). Furthermore, the
      preischemic CsA-treated muscle group demonstrated decreased edema (1.137 +/-
      0.095 times the contralateral nonischemic muscle) when compared with the control
      ischemic muscle group (1.248 +/- 0.045 times the contralateral nonischemic
      muscle; p = 0.011). Although a trend toward improved muscle viability (32.1 +/-
      4.2%) and decreased edema formation (1.200 +/- 0.062 times the contralateral
      nonischemic muscle) was observed in the peri-ischemic CsA-treated group when
      compared with the control ischemic muscle group, these differences were not
      significant. These observations confirm the beneficial effects of preischemic CsA
      therapy observed in organ transplantation research and suggest limited clinical
      use of peri-ischemic CsA therapy for patients with musculoskeletal amputations.

PMID- 11324888
TI  - Salvage of avascular bone from frostbite with free tissue transfer.
AB  - Traditional management of frostbite injury of the hands and fingers has been to
      allow demarcation to occur between viable and nonviable tissues, corresponding to
      the level of amputation required. In this case report, phalangeal length in
      mummified digits was maintained with free tissue transfer followed by evidence of
      bony revascularization on bone scan. Rather than waiting for tissue demarcation
      to occur, the authors propose that consideration be given to debridement of soft
      tissues in the frostbitten fingers followed by free tissue transfer to salvage
      length and function in the digital bony skeleton.

PMID- 11324889
TI  - Composite grafting and hyperbaric oxygen therapy in pediatric nasal tip
      reconstruction after avulsive dog-bite injury.
AB  - It is estimated that more than four million people are bitten by dogs in the
      United States each year. The majority of such injuries are minor, and their
      treatment does not usually require surgical consultation. However, the authors
      report a case in which a Rottweiler inflicted a mutilating nasal tip/alar rim
      avulsion on a 5-year-old boy. They report their experience with immediate
      reconstruction of the nasal defect using a large ipsilateral auricular cartilage
      composite graft (crus helix). Adjunctive hyperbaric oxygen therapy (without
      sedation or anesthesia) was used to maximize the stimulus for graft
      revascularization. Reconstructive goals were achieved while avoiding the need for
      a central facial donor site defect.

PMID- 11324890
TI  - Microsurgical ear replantation without venous repair: failure of development of
      venous channels despite patency of arterial anastomosis for 14 days.
AB  - The authors describe a case of microvascular ear replantation with repair of the
      artery only and medicinal leech therapy that survived for 14 days but ultimately
      failed as a result of the absence of development of venous channels between the
      replant and the recipient bed. A 35-year-old man presented with complete avulsion
      of 80% of the right external ear. The auricle was revascularized successfully via
      transposition of the superficial temporal artery (STA) and end-to-end anastomosis
      between the STA and an identified arterial branch on the posterior surface of the
      ear, using the technique of longitudinal wedge resection. No suitable veins could
      be found, therefore medicinal leech therapy was used for venous drainage as well
      as for systemic heparinization. Although the replant remained viable, frequency
      of leeching did not decrease over 2 weeks. On postoperative day 14, despite
      obvious viability of the replanted ear, leeching was stopped, considering the
      ongoing blood loss. Unfortunately, the auricle was found to be necrosed totally
      the following day. In retrospect, the authors think that inadequate debridement
      of nonvital tissues may have led to the failure of development of venous channels
      between the replant and the recipient bed, as manifested by the frequent
      requirement of leeching to relieve venous congestion long after
      revascularization. They conclude that the importance of thorough debridement
      cannot be overemphasized in microsurgical ear replantation with no vein
      anastomosis, as demonstrated in their patient. From the point of view of creation
      of venous drainage channels, deepithelialization of the posterior ear skin may be
      beneficial.

PMID- 11324891
TI  - Reversed dorsal digital and metacarpal island flaps supplied by the dorsal
      cutaneous branches of the palmar digital artery.
AB  - The dorsal digital and metacarpal island flaps have been described for use in a
      variety of clinical situations. On the basis of the authors' previous
      angiographic studies, these two skin flaps were planned on the dorsum of the
      proximal phalanx or intermetacarpal space based on the vascular anastomoses
      between the proximal dorsal cutaneous branches of the palmar digital artery and
      the dorsal digital branches of the dorsal metacarpal artery at the level of the
      proximal phalanx. The authors present a series of 13 patients using these flaps.
      To reconstruct the injured finger pulp, the reverse dorsal digital flap was used
      in 5 patients, and the reverse dorsal metacarpal flap was used in 8 patients.
      Most of the 13 patients sustained a work-related injury. Associated injuries of
      bone, joint, or tendon occurred in most patients. In all patients, the skin
      defect was located distal to the proximal interphalangeal joint. The skin paddle
      was taken from the dorsal aspect of the middle and ring fingers or the first,
      second, third, and fourth metacarpal area. All flaps survived completely. Two
      patients who had the dorsal branch of the sensitive radial nerve anastomosed to
      the digital nerve recovered 6-mm two-point discrimination in the reverse dorsal
      digital flap. The results of this anatomic study and the authors' clinical
      experience confirm the reliability of the dorsal digital and metacarpal island
      flaps.

PMID- 11324892
TI  - One-stage facial augmentation with an intraoral groin adipose flap transfer.
AB  - A free groin adipose flap using an intraoral approach was used to correct facial
      contour deformities instead of a groin dermis-fat flap. The major disadvantages
      of the latter flap are that multistage debulking procedures are required and
      there are wide postoperative donor scars because of the wide skin portion
      included in the flap. To overcome these weaknesses the authors developed a free
      groin, customized ("berry picked") adipose flap, which was transferred by an
      intraoral approach for reconstruction of congenital hemifacial (orbitozygomatic)
      hypoplasia. The advantages of this method include one-stage augmentation without
      secondary defatting, no skin grafting of the donor defect, a donor scar in a
      concealed area, and possible transfer through an intraoral approach that results
      in minimal invasive surgery with no scar at the graft site.

PMID- 11324893
TI  - Bends of the breast: is it possible?

PMID- 11324894
TI  - Cutaneous anthrax of the eyelid.

PMID- 11324895
TI  - Salvage of flaps with venous congestion.

PMID- 11324896
TI  - Squamous cell carcinoma affecting the nose and lower lip.

PMID- 11324897
TI  - Dystrophic calcinosis cutis in a patient with squamous cell carcinoma secondary
      to postburn scar.

PMID- 11324898
TI  - Going back to your roots.

PMID- 11324899
TI  - Inhalation of (1-->3)-beta-D-glucan causes airway eosinophilia.
AB  - BACKGROUND: Moulds are present in a variety of environments and aerosols of
      fungal spores are generated when mouldy materials are handled. Molds contain (1-
      >3)-beta-D-glucan, a polyglucose which is present in the cell wall of fungi,
      certain bacteria and plants. AIM: This study was undertaken to investigate the
      cellular inflammatory response in the lung after inhalation of (1-->3)-beta-D
      glucan and bacterial endotoxin. METHODS: Guinea pigs were exposed daily to an
      aerosol of pure (1-->3)-beta-D-glucan and pure endotoxin for five weeks. Lung
      lavage and lung interstitial cell preparations were done and the inflammatory
      cells counted. Histological sections were prepared from the trachea. RESULTS:
      There was an increase in eosinophil numbers in lung lavage, lung interstitium,
      and the airway epithelium of animals exposed to (1-->3)-beta-D-glucan. In animals
      simultaneously exposed to endotoxin, there was no increase in eosinophils. In the
      lung interstitium, (1-->3)-beta-D-glucan exposure caused an increase in
      lymphocytes, which was not found after endotoxin exposure. Endotoxin exposure
      caused an increase in neutrophils and macrophages in lung lavage, which was not
      found after (1-->3)-beta-D-glucan exposure. CONCLUSIONS: The results support
      previous findings that (1-->3)-beta-D-glucan causes a different response in the
      airways as compared to endotoxin. Endotoxin modulated the increase in eosinophils
      caused by (1-->3)-beta-D-glucan exposure, suggesting a complex interaction
      between the microbial cell wall components.

PMID- 11324900
TI  - Effects of fluticasone propionate inhalation on levels of arachidonic acid
      metabolites in patients with chronic obstructive pulmonary disease.
AB  - BACKGROUND: In smoking COPD patients the bronchoalveolar lavage (BAL) fluid
      contains high numbers of inflammatory cells. These cells might produce
      arachidonic acid (AA) metabolites, which contribute to inflammation and an
      increased bronchomotor tone. AIMS: To investigate levels of AA metabolites in BAL
      fluid, before and after inhaled glucocorticoid therapy: fluticasone propionate
      (FP) 1 mg per day, or placebo. METHODS: A double-blind placebo controlled trial
      lasting six months. COPD patients were selected by clinical criteria and the
      presence of bronchial hyper-responsiveness (BHR). Lung function was recorded and
      in BAL fluid we counted cell numbers and measured LTB4, LTC4/D4/E4, PGE2,
      6kPGF1alpha, PGF2alpha and TxB2. A control group consisted of asymptomatic
      smokers (n=6). RESULTS: Paired data were obtained from 9 FP treated and 11
      placebo patients. BAL cells were almost exclusively alveolar macrophages. In
      patients and controls both cellularity and levels of AA metabolites were equal
      Cell numbers did not change after treatment. Statistically significant decreases
      after FP therapy were noticed for PGE2 (30%), 6kPGF1alpha (41%) and PGF2alpha
      (54%). CONCLUSIONS: In COPD, the capability of inflammatory cells to produce
      certain AA metabolites was decreased after inhaled FP treatment. This result is
      discussed in its relation to clinical effects, the influence of smoking, and the
      results of an earlier, similar study in asthma patients.

PMID- 11324901
TI  - In-vitro activation of complement system by lactic acidosis in newborn and
      adults.
AB  - INTRODUCTION: Complement activation occurs secondary to a variety of external
      stimuli. Lactic acidosis has been previously shown to activate the complement
      factors C3a and C5a. In the present investigation we examined the differential
      effect of lactic acidosis on anaphylatoxin levels in cord and adult blood.
      Furthermore we aimed to determine if the entire complement cascade could be
      activated by lactic acidosis. METHODS: Cord and adult blood samples (n = 20 each)
      were collected and incubated for one hour in either untreated condition or with
      the addition of lactate in two concentrations (5.5 mmol/l vs. 22 mmol/l).
      Following incubation, levels of C3a, C5a and sC5b-9, and blood gas parameters
      were determined. RESULTS: Anaphylatoxin (C3a and C5a) and sC5b-9 levels increased
      with the addition of lactate in a dose-dependent manner in cord and adult blood
      (C3a: 1 h, 5.5 mmo/l, 22 mmol/l: 418/498/622 microg/l in cord blood;
      1010/1056/1381 microg/l in adult blood, p<0,05; similar results were found for
      C5a and sC5b-9). CONCLUSION: Lactic acidosis leads to an activation of the entire
      complement system in neonates and in adults. This activation is dose-dependent
      and more pronounced in adults as compared to neonates.

PMID- 11324902
TI  - MUC5AC mucin release from human airways in vitro: effects of indomethacin and Bay
      X1005.
AB  - BACKGROUND: Increased secretion of mucus is a hallmark of many respiratory
      diseases and contributes significantly to the airflow limitation experienced by
      many patients. While the current pharmacological approach to reducing mucus and
      sputum production in patients is limited, clinical studies have suggested that
      drugs which inhibit the cyclooxygenase and/or 5-lipoxygenase enzymatic pathways
      may reduce secretory activity in patients with airway disease. AIM: This study
      was performed to investigate the effects of indomethacin (cyclooxygenase
      inhibitor) and Bay x 1005 (5-lipoxygenase inhibitor) on MUC5AC release from human
      airways in vitro. METHODS: An immunoradiometric assay was used to determine the
      quantities of MUC5AC present in the biological fluids derived from human airways
      in vitro. The measurements were made with a mixture of eight monoclonal
      antibodies (MAbs; PM8) of which the 21 M1 MAb recognized a recombinant M1 mucin
      partially encoded by the MUC5AC gene. RESULTS: The quantities of MUC5AC detected
      in the biological fluids derived from human bronchial preparations were not
      modified after treatment with indomethacin (cyclooxygenase inhibitor) and/or an
      inhibitor of the 5-lipoxygenase metabolic pathway (BAY x 1005). CONCLUSION: These
      results suggest that the cyclooxygenase and 5-lipoxygenase metabolic pathways
      play little or no role in the release of MUC5AC from human airways.

PMID- 11324903
TI  - Recurrence of hepatitis C after liver transplantation is associated with
      increased systemic IL-10 levels.
AB  - BACKGROUND: Recurrence of hepatitis C after liver transplantation is an almost
      universal occurrence. T-cell derived cytokines have an important role in the
      development of liver damage associated with chronic hepatitis C, their post
      transplant levels, however, have not been correlated with histologic recurrence
      of the disease. AIMS: We sought to analyze levels of TNF-alpha, soluble IL-2
      receptor, IL-4 and IL-10 at 1 month, 6 months and 1 year after transplantation in
      27 patients undergoing transplantation for hepatitis C related end-stage liver
      disease. METHODS: HCV RNA levels were monitored by a branched-chain DNA signal
      amplification assay. Diagnosis of recurrent hepatitis was based on 1-year
      protocol biopsies and on biopsies performed for liver enzyme elevations. RESULTS:
      Recurrent hepatitis C was detected in 52% (n=14) of the 27 patients. HCV RNA
      levels rose over time in all patients regardless of histologic recurrence. TNF
      alpha, and IL-4 levels, although elevated, did not show specific patterns over
      time or in correlation with recurrence. Similarly, the early elevation followed
      by a gradual decrease over the first year in the amount of soluble IL-2 receptor
      was not related to histologic recurrence. We observed a significant increase in
      circulating IL-10 levels over the first year in patients with biopsy-proven
      recurrence, while patients with no signs of histologic recurrence displayed
      increased, but steady levels. CONCLUSIONS: These results suggest that while these
      cytokines are associated with post-transplant recurrence of hepatitis C, their
      production may be altered by additional factors.

PMID- 11324904
TI  - Blood histamine levels (BHL) in infants and children with respiratory and non
      respiratory diseases.
AB  - BACKGROUND: Blood histamine levels are decreased after severe allergic reactions
      and in various chronic diseases. AIMS: To study blood histamine levels in infants
      and children with acute infectious and non-infectious, non-allergic, disease.
      METHODS: Blood histamine levels were investigated by a fluorometric method in
      infants and children admitted to hospital with bronchiolitis, non-wheezing
      bronchitis, acute infections of the urinary tract, skin and ear-nose-throat,
      gastroenteritis, or hyperthermia of unknown aetiology. Results of blood histamine
      levels and white blood cell counts were compared with those obtained for children
      recovering from benign non-infectious, non-allergic illnesses. RESULTS: As
      compared with control children, white blood cell numbers were significantly
      increased in children with acute infections of the urinary tract, skin and ear
      nose-throat, and were significantly decreased in children with gastroenteritis.
      Blood histamine levels were significantly lower in children with gastroenteritis
      and hyperthermia than in children with other diseases and control children. It
      was not possible to correlate blood histamine levels and the number of blood
      basophils. CONCLUSIONS: BHL are significantly decreased in infants and children
      with acute gastroenteritis and hyperthermia of unknown aetiology. The mechanisms
      responsible for the decrease in blood histamine levels in children with
      gastroenteritis and hyperthermia are discussed.

PMID- 11324905
TI  - Concentricol, a taxonomically significant triterpenoid from Daldinia concentrica.
AB  - In the course of a chemotaxonomic study of xylariaceous Ascomycetes, a major
      metabolite was isolated and identified from the ascostromata of Daldinia
      concentrica. The compound, for which the name concentricol is proposed,
      constitutes a highly oxidised squalene derivative. A survey of several Daldinia
      spp. from around the world (including several type materials), employing
      analytical HPLC-UV/Vis (with diode array detection) and positive electrospray
      HPLC-MS of stromatal MeOH extracts revealed that concentricol was omnipresent in
      the stromata of D. concentrica, as well as in those of several collections of the
      pantropical Daldinia eschscholzii. All other investigated Daldinia spp. were
      found devoid of concentricol but contained binaphthalenes, benzophenones and/or
      azaphilones as further taxonomically relevant main metabolites.

PMID- 11324906
TI  - Tetra-unsaturated sesterterpenoids (Haslenes) from Haslea ostrearia and related
      species.
AB  - The structures and distributions of C25 highly branched isoprenoid (HBI) alkenes
      (Haslenes) have been determined following isolation from cultures of the diatoms
      Haslea ostrearia, Haslea crucigera, Haslea pseudostrearia and Haslea saltstonica.
      The distributions of the HBIs change between Haslea species and also between
      different cultures of the same species. Large scale culturing of H. ostrearia and
      H. pseudostrearia has enabled the structures of three new tetra-unsaturated
      alkenes to be determined by NMR spectroscopy. The structural relationships
      between different Haslenes together with the potential significance of the
      biosynthesis of HBIs by the Haslea genus is discussed.

PMID- 11324907
TI  - Sterols from the fungus Lactarium volemus.
AB  - Seven ergostane-type sterols and two mono-glucosides were isolated from the ethyl
      acetate soluble fraction of Lactarium rolemus. Three are previously unknown, i.e.
      3-O-beta-D-glucopyranosyl-22E,24R-5alpha,8alpha-epidioxyergosta-6,22-diene, 3-O
      beta-D-glucopyranosyl-22E,24R-5beta,8beta-epidioxyergosta-6,22-diene and 22E,24R
      ergosta-7,22-diene-3beta,5alpha,6beta,9alpha-tetraol. The structural elucidation
      of these compounds was mainly achieved by spectroscopic methods.

PMID- 11324908
TI  - seco-Cuparane-type sesquiterpenoid from the Japanese liverwort Jungermannia
      infusca.
AB  - A 2,3-seco-cuparane-type sesquiterpenoid and the previously known barbatane-type
      sesqui- and ent-kaurane-type diterpenoids were isolated from the Japanese
      liverwort Jungermannia infusca (Mitt.) Steph. The structure of the 2,3-seco
      cuparane-type sesquiterpenoid was determined by NMR spectroscopic analyses.

PMID- 11324909
TI  - Labdane and pimarane diterpenes from Croton joufra.
AB  - From the chloroform extract of the leaves of Croton joufra, the diterpenes
      2alpha,3alpha-dihydroxy-labda-8(17),12(13),14(15)-triene and 3beta-hydroxy-19-O
      acetyl-pimara-8(9),15-dien-7-one, were isolated. Their structures were
      established by spectroscopic methods. One of the compounds showed weak lethality
      in the brine shrimp assay.

PMID- 11324910
TI  - Dammarane derivatives from the dried fruits of Forsythia suspensa.
AB  - Anti-inflammatory activity guided fractionation of the n-hexane soluble fraction
      of a 70% aqueous methanolic extract of the dried fruits of Forsythia suspensa
      afforded two new triterpenes. The structures of these compounds were elucidated
      as 3beta-acetyl-20,25-epoxydammarane-24alpha-ol (1) and 3beta-acetyl-20,25
      epoxydammarane-24beta-ol (2) on the basis of spectral data interpretation as well
      as by comparison with those of structurally similar compounds.

PMID- 11324911
TI  - The (3R,9R)-3-hydroxy-7,8-dihydro-beta-ionol disaccharide glycoside is an aroma
      precursor in tea leaves.
AB  - The disaccharide glycoside, (3R,9R)-3-hydroxy-7,8-dihydro-beta-ionyl 6-O-beta-D
      apiofuranosyl-beta-D-glucopyranoside was isolated as an aroma precursor from the
      leaves of Camellia sinensis var. sinensis cv. Yabukita. Its stereochemistry was
      elucidated on the basis of spectral data and chemical synthesis.

PMID- 11324912
TI  - Constituents of Afzelia bella stem bark.
AB  - The stembark of Afzelia bella yielded an acylated dihydroflavonol glycoside
      identified as 2R,3R-trans-aromadendrin-7-O-beta-D-glucopyranoside-6''-(4''
      hydroxy-2''-methylene butanoate), along with five known flavonoids and the lignan
      glycoside (+)-isolariciresinol 9-O-xyloside. Their structures were determined by
      detailed 1D and 2D NMR analyses.

PMID- 11324913
TI  - 3-Desoxyanthocyanidins from Arrabidaea chica.
AB  - The new 3-desoxyanthocyanidins 6,7,3'-trihydroxy-5,4'-dimethoxy-flavylium and
      6,7,3',4'-tetrahydroxy-5-methoxy-flavylium and the known 6,7-dihydroxy-5,4'
      dimethoxy-flavylium (Carajurin) were isolated by bioguided fractionation from the
      leaves of Arrabidaea chica, with transcription factor NF-kappaB as target. The
      structure of Carajurone was revised to be 6,7,4'-trihydroxy-5-methoxy-flavylium.
      Additionally, the flavone acacetin was found. All structures were mainly
      established on the basis of MS- and NMR data (1H, 1H-1H COSY and partly 13C,
      GHMQCR and GHSQCR). Carajurin, which failed to give a positive result in the DPPH
      TLC assay completely inhibited NF-kappaB, but not NF-AT at a 500 microM
      concentration.

PMID- 11324914
TI  - Flavonoids from the stem bark of Bolusanthus speciosus.
AB  - Three flavonoids (bolusanthols A-C), viz an isoflavan and two prenylated
      isoflavanones, were isolated from the stem bark of Bolusanthus speciosus in
      addition to four known flavonoids, 5,7,3'-trihydroxy-4'-methoxy-5'-methoxy
      gamma,gamma-dimethylallylisoflavanone, 5,7,2'-trihydroxy-4'-methoxy-6,5'
      di(gamma,gamma)-dimethylallyl)isoflavanone, 3,5,7,3',4'-pentahydroxy-6
      gamma,gamma-dimethylallylflavone and 5,7,2',4'-tetrahydroxy-8,3'-di(gamma,gamma
      dimethylallyl)-isoflavanone. The structure of the new compounds were determined
      to be 4,2',3',4'-tetrahydroxy-6,7-methylenedioxyisoflavan (bolusanthol A),
      5,7,3',4'-tetrahydroxy-5'-gamma,gamma-dimethylallylisoflavanone (bolusanthol B),
      and 5,7,4'-trihydroxy-6,3'-di(gamma,gamma-dimethylallyl)isoflavanone (bolusanthol
      C) by spectroscopic methods.

PMID- 11324915
TI  - Identification of a sucrose diester of a substituted beta-truxinic acid in oats.
AB  - A novel compound, 4,4'-dihydroxy-3,3'-dimethoxy-beta-truxinic acid esterified to
      sucrose through the fructosyl 3-and 6-carbons (1), was isolated from oat grains
      (Avena sativa L.). Its structure was determined by a combination of mass
      spectrometry and 1-D and 2-D NMR. The amounts of 1 in groats of six different oat
      cultivars ranged from 101 to 150 microg g(-1) (dry wt). None was detected in the
      hulls. The free diacid, 4,4'-dihydroxy-3,3'-dimethoxy-beta-truxinic acid (2),
      could not be detected in groats nor in hulls.

PMID- 11324916
TI  - Bianthraquinones from Cassia siamea.
AB  - The isolation of two bianthraquinones, 1,1',3,8,8'-pentahydroxy-3',6
      dimethyl[2,2'-bianthracene]-9,9',10,10'-tetrone and 7-chloro-1,1',6,8,8'
      pentahydroxy-3,3'-dimethyl[2,2'-bianthracene]-9,9',10,10'-tetrone, from the root
      bark of Cassia siamea is reported. The structures were established by analysis of
      spectroscopic data and 7-chloro-1,1',6,8,8'-pentahydroxy-3,3'-dimethyl[2,2'
      bianthracene]-9,9',10,10'-tetrone was determined on the direct comparison with
      synthetic compound.

PMID- 11324917
TI  - Xanthones and flavonoids from Leiothrix curvifolia and Leiothrix flavescens.
AB  - 8-Carboxymethyl-1,6-dihydroxy-3,5-dimethoxyxanthone, 8-carboxymethyl-1,5,6
      trihydroxy-3-methoxyxanthone and 8-carboxymethyl-1,3,5,6-tetrahydroxyxanthone
      were isolated from the capitula of Leiothrix curvifolia and Leiothrix flavescens
      and characterized by spectroscopic methods, mainly 1D and 2D NMR experiments, as
      well as by electrospray mass spectrometry. Eight known flavonoids were also
      isolated and they were identified by 1D and 2D NMR experiments and comparison
      with literature data.

PMID- 11324918
TI  - Antimicrobial alkaloids from Zanthoxylum tetraspermum and caudatum.
AB  - Two benzophenanthrene alkaloids, 8-acetonyldihydronitidine and 8
      acetonyldihydroavicine were isolated from Zanthoxylum tetraspermum stem bark
      along with liriodenine, sesamin, lichexanthone and (+)-piperitol-gamma,gamma
      dimethylallylether. The species endemic to Sri Lanka, Z. caudatum, contained
      sesamin, savinin, liriodenine, decarine and 8-O-desmethyl-N-nornitidine. 8
      Acetonyldihydronitidine and 8-acetonyldihydroavicine showed significant
      antibacterial activity while the former along with liriodenine was strongly
      antifungal. Savinin exhibited potent spermicidal activity. Both savinin and
      sesamin exhibited significant insecticidal activity.

PMID- 11324919
TI  - The co-occurrence of C(3) epimer Nb,C(21)-secocuran alkaloids in Strychnos
      diplotricha and Strychnos myrtoides.
AB  - From the stem bark of Strychnos diplotricha, three Nb,C(21)-secocuran alkaloids,
      viz., 3-epi-myrtoidine, 11-demethoxy-3-epi-myrtoidine and 11-demethoxy-12-hydroxy
      3-epi-myrtoidine, were isolated together with the known myrtoidine and 11
      demethoxymyrtoidine. They also occur in different parts of S. myrtoides.

PMID- 11324920
TI  - Bromoallenic lipid compounds from lichens of central Asia.
AB  - The composition of two bromoallenic aliphatic fatty acids obtained from lichens
      collected around Lake Issyk-Kul (central Asia) is described. These compounds were
      identified by means of 1H and 13C NMR, MS and IR spectra.

PMID- 11324921
TI  - Triterpene and flavanone glycoside from Rhododendron simsii.
AB  - Antioxidative substances were isolated from the leaves of Rhododendron simsii.
      These were a triterpene and flavanone glycoside, together with the known
      matteucinol and two known benzoic acid derivatives. Their structures were
      characterized as 19,24-dihydroxyurs-12-en-3-one-28-oic acid and 7-O-beta-D
      apiofuranosyl-(1-->6)-beta-D-glucopyranosylmatteucinol by spectroscopic analysis.

PMID- 11324922
TI  - Passifloricins, polyketides alpha-pyrones from Passiflora foetida resin.
AB  - Three polyketides alpha-pyrones, named passifloricins, were isolated from
      Passiflora foetida resin; their structures and relative configurations were
      assigned through 2D NMR spectroscopic analyses. These types of compounds were not
      detected in other passion flowers.

PMID- 11324923
TI  - Autoantibodies to filaggrin/deiminated fibrin (AFA) are useful for the diagnosis
      and prognosis of rheumatoid arthritis, and are probably involved in the
      pathophysiology of the disease.

PMID- 11324924
TI  - TNFalpha inhibition in psoriatic arthritis: cause for hope.

PMID- 11324925
TI  - Ethical aspects of gene therapy in rheumatology.

PMID- 11324926
TI  - Bone status in primary hyperparathyroidism.
AB  - Traditional bone involvement, such as osteoitis fibrosa, has become very rare (<
      1%) in primary hyperparathyroidism (PHPT); nevertheless, fractures seem more
      frequent than in controls, with a predilection for fractures of the distal
      extremity of the radius, pelvis, ribs and vertebrae, and a relative modest
      incidence of fractures of the upper extremity of the femur. Histo-morphometric
      studies have stressed a discrepancy between cortical and trabecular bone with an
      increase of bone remodeling. The cortical width is constantly diminished and the
      cortical porosity is increased whereas trabecular volume is normal and micro
      architecture preserved. Bone mineral density (BMD) allows an early diagnosis of
      bone disease and takes a growing place in the management of patients. Since the
      consensus conference in 1991, the measurement of BMD has been incorporated in the
      surgical decision with a threshold: Z-score < -2. The demineralisation
      predominates on sites rich in cortical bone (1/3 proximal of the distal radius);
      the radius, which was the first site evaluated for technical reasons, is also the
      most discriminating one. Spine demineralisation is met in more severe forms and
      BMD measurement of the whole body is promising but requires more studies. In the
      absence of a radical processing, moderate forms remain stable, whereas more
      severe forms have a tendency to deteriorate. The evaluation of spine and femoral
      BMD is useful for the follow-up because the bone gain after parathyroidectomy is
      significant early on at these sites (rich in trabecular bone with high bone
      turnover), whereas the BMD of radius is relatively stable.

PMID- 11324927
TI  - Adult hypophosphatasia. Current aspects.
AB  - Hypophosphatasia is an inborn metabolic disorder in which abnormally low levels
      of the enzyme nonspecific alkaline phosphatase result in defective skeletal and
      dental mineralization (rickets, fractures, dental abnormalities) and in
      accumulation of the enzyme substrates (phosphoethanolamine, pyridoxal-5'phosphate
      and inorganic pyrophosphate). The build-up of inorganic pyrophosphate promotes
      the development of articular chondrocalcinosis. There are several forms of
      hypophosphatasia, with wide variations in severity. We report the case of a 53
      year-old man with typical manifestations of moderate adulthood hypophosphatasia.
      Investigations in his family found the disease in a sister and two children. He
      had two autosomal mutations, which were transmitted recessively. Several
      mutations of the alkaline phosphatase gene have been identified. The genotype is
      correlated with the phenotype: some mutations are associated with milder forms
      and others with more severe forms of the disease.

PMID- 11324928
TI  - Osteogenesis imperfecta: lifelong management is imperative and feasible.
AB  - Osteogenesis imperfecta is a group of inherited diseases responsible for varying
      degrees of skeletal fragility. Minimal trauma is sufficient to cause fractures
      and bone deformities. The classification of osteogenesis imperfecta has recently
      been improved by the inclusion of additional clinical and histomorphometric data.
      The diagnosis is often readily made in infancy; some cases, however, go
      unrecognized until adulthood. Lifelong multidisciplinary management is
      imperative. Pamidronate therapy in childhood is the most extensively studied
      treatment and has been proved beneficial. Other bisphosphonates are being
      evaluated, particularly in adults. Prevention of vitamin D and calcium deficiency
      is essential throughout life. Pain is common and should be given adequate
      attention.

PMID- 11324929
TI  - The first description of rheumatoid arthritis. Unabridged text of the doctoral
      dissertation presented in 1800.
AB  - This unabridged version of the dissertation presented in 1800 by Augustin Jacob
      Landre-Beauvais for his medical doctorate describes a disease different in many
      ways from the condition known since Hippocrates as gout. The patients were nine
      long-term residents of the Salpetriere hospice in Paris. After reviewing the main
      features of ordinary or regular gout, Landre-Beauvais points out that the disease
      he calls "asthenic gout" exhibits several distinctive features, including
      predominance in women, a chronic course, involvement of many joints from the
      onset, and a decline in general health. Despite the tentative tone of his title
      ("Should one recognize...), he clearly is convinced that he is describing an as
      yet unreported entity, as indicated by the last sentence of his dissertation:
      "...we must recognize the existence of a new form of gout under the designation
      primary asthenic gout" And although he stops short of emancipation from the term
      "gout", which had been used for centuries to designate specific joint
      manifestations, he makes several keenly discerning observations -- particularly
      regarding the influence of psychological factors, the need for gentle treatments,
      and the inappropriateness of bloodletting - thus breaking free from contemporary
      doctrine. This text is acknowledged as the first description of rheumatoid
      arthritis. A brief biography of Landre-Beauvais is provided.

PMID- 11324930
TI  - Rheumatoid factors, anti-filaggrin antibodies and low in vitro interleukin-2 and
      interferon-gamma production are useful immunological markers for early diagnosis
      of community cases of rheumatoid arthritis. A preliminary study.
AB  - OBJECTIVE: To determine whether measurements of different autoantibodies (Ab) and
      cytokines are useful to distinguish very early rheumatoid arthritis (RA) from
      other inflammatory rheumatisms. METHODS: From a population-based recruitment, 32
      patients with very early polyarthritis (median duration: 4 months) were studied.
      Evaluations at entry (M0), and at 6 (M6) and 12 months (M12). Ab tested:
      rheumatoid factors (RF) by agglutination methods and ELISA, antiperinuclear
      factor (APF), antikeratin Ab (AKA), anti-Sa and antinuclear Ab. Cytokine
      production (TNFalpha, IL2, IFNgamma, IL1beta, IL10) in whole blood cell culture
      (WBCC) was determined at M0. At M12, patients were classified as having RA (N =
      15) or other rheumatic diseases. RESULTS: At M0, AKA/APF and anti-Sa Ab
      frequencies were low, 13% and 7%, respectively. While most Ab detected at M0
      persisted, others appeared during follow-up, particularly APF, which rose from 13
      to 40% at M12. At M6, IgM-RF was detected in two RA patients exclusively by
      ELISA. AKA/APF were found to be highly specific markers for RA (100%
      specificity). At some time during follow-up, two RF-negative RA patients were AKA
      positive. In two patients, AKA and APF were present at M0 before they satisfied
      ACR criteria. IL2 and IFNgamma production was significantly lower (P < 0.05) for
      RA patients. CONCLUSION: AKA/APF and anti-Sa Ab were detected in community cases
      of very early RA. AKA/APF and RF detected by ELISA might contribute to an earlier
      diagnosis of RA. Low production of IFNgamma and IL2 in WBCC constituted a
      distinct immunopathological feature in very early RA patients.

PMID- 11324931
TI  - Relationship of ankle joint involvement with subtalar destruction in patients
      with rheumatoid arthritis. A 20-year follow-up study.
AB  - AIMS: In the present study we evaluated radiographically involvement of the ankle
      joint and its relationship to destruction of the subtalar joint in rheumatoid
      arthritis (RA). METHODS: An inception cohort of 103 patients with seropositive RA
      was followed over a period of 20 years. Follow-up examinations were conducted
      after onset, 1, 3, 8, 15, and 20 years from entry. A total of 83 patients
      attended the 15-year and 68 patients the 20-year follow-up. Radiographic
      evaluation was performed using a lateral weight-bearing ankle radiograph. A
      simplified grading was applied for the talocrural joint, in which the ankles
      (patients) were divided into three groups: no changes, minor changes and major
      changes. In the end-point analysis the last radiograph was assigned. Subtalar
      destruction was recorded (Larsen grade > or = 2). Severity of RA in different
      groups was evaluated using the Larsen score of 0-100 of hands and feet.
      Difference between patient groups was evaluated using Cuzick's test. RESULTS: At
      the endpoint major changes of the ankles were detected in seven patients (7%)
      only, minor changes were observed in 17 patients (16%). The first minor
      involvement of the ankle was observed at the three-year follow-up in two
      patients. First major changes were detected at the 15-year follow-up in three
      ankles of two patients. Subtalar pathology preceded that of TC joint in all
      ankles with major changes. In 17 patients with minor changes, simultaneous
      subtalar pathology was observed in all but two ankles, while preceding subtalar
      involvement was radiographically manifest in 13 of 21 ankles. The means of Larsen
      scores of 0-100 were in the three ankle grading groups 40, 54 and 63,
      respectively. Cuzick's test for the trend was highly significant (P < 0.001). No
      reconstructive surgery was performed on the ankle joint during the follow-up,
      whereas the subtalar joint complex was fused cumulatively in 12 patients.
      CONCLUSIONS: The ankle joint is involved in a late stage of RA and is usually
      affected only in the patients with severe disease. Subtalar pathology precedes
      the changes in the talocrural joint almost regularly.

PMID- 11324932
TI  - Six cases of cervical ligamentum flavum calcification in Blacks in the French
      West Indies.
AB  - OBJECTIVE: Calcification of the ligamentum flavum at the cervical spine is an
      uncommon condition reported mainly in Japanese patients. We describe the clinical
      manifestations, imaging study findings, and outcomes in six cases seen in the
      French West Indies. MATERIAL AND METHODS: We retrospectively reviewed the medical
      charts of six patients admitted to an orthopedics department for spinal cord
      compression shown upon computed tomography to be caused by calcification of the
      ligamentu flavum. There were five women and one man, mean age at admission was
      71.7 years (range, 64-79 years) and all six patients were Black. RESULTS: Five
      patients had cervical myelopathy and one was asymptomatic. All five symptomatic
      patients had cervical spinal stenosis, explaining the rapid symptom onset (within
      six and a half months) and severe motor loss. Computed tomography reconstruction
      in the sagittal plane ruled out ossification of the ligamentum flavum. Magnetic
      resonance imaging of the neck failed to demonstrate the calcifications but was
      useful in evaluating the severity of the spinal cord compression. One patient had
      articular chondrocalcinosis in both knees and another had calcifications in the
      basal ganglia. Surgical decompression by the posterior route was performed in two
      patients and was effective in both, whereas two of the three symptomatic patients
      who did not have surgery experienced worsening neurological loss. Analysis of the
      operative specimens from the two surgically treated patients showed a mixture of
      calcium pyrophosphate dihydrate crystals and apatite microcrystals. CONCLUSION:
      Calcification of the ligamentum flavum is probably underrecognized in blacks.
      This condition causes severe neurological loss. Imaging studies provide the
      diagnosis. The pathogenesis remains unclear.

PMID- 11324933
TI  - Arthropathy associated with anti-Jo-1 antibody.
AB  - Anti-Jo-1 antibody is associated with an overlap syndrome usually described as
      the association of idiopathic inflammatory myopathy, pulmonary fibrosis and
      polyarthritis. We report three observations illustrating different aspects of
      arthropathy associated with anti-Jo-1 antibody. Two patients presented with a
      deforming and erosive arthritis affecting the hands, periarticular calcifications
      and dislocation of the interphalangeal (IP) joint of the thumb. The third
      patient, who had a short disease course, presented only with a mild non-erosive
      polyarthritis of both hands, metacarpophalangeal joint narrowing and
      periarticular calcifications. All the patients had interstitial pulmonary
      syndrome. Only two of them had myositis. An arthropathy characterized by erosive
      arthritis of the fingers, with dislocation of the IP joint of the thumb and
      periarticular calcifications, seems to be specifically associated with anti-Jo-1
      antibody.

PMID- 11324934
TI  - Cranial nerve palsy revealing an occipitovertebral metastasis from carcinoma of
      the uterine cervix.
AB  - A 37-year-old woman had a histologically documented occipitovertebral metastasis
      from an invasive epidermoid carcinoma of the uterine cervix. The metastasis was
      found 3 months after the primary and was treated by local radiation therapy
      followed by systemic chemotherapy. Radiation therapy was highly effective in
      relieving the pain but was not associated with changes in magnetic resonance
      imaging findings. Lymph node involvement and local extension occurred. The
      patient died 1 year after the diagnosis of the metastasis. Involvement of the
      occipitovertebral junction by uterine cervix carcinoma metastasis is exceedingly
      rare. The relevant literature is reviewed.

PMID- 11324935
TI  - Management of a patient with sarcoid calcaneitis and dactylitis.
AB  - Dactylitis and calcaneitis developed in a patient with untreated sarcoidosis of
      the skin and lungs. Radiographs showed a defect in the second phalanx of the left
      middle finger. Radiographs of the feet were normal, but magnetic resonance
      imaging demonstrated a defect in the left calcaneus. Methylprednisolone therapy
      (1 g per day for 3 consecutive days) induced a dramatic improvement within 48
      hours. Low-dose oral glucocorticoid therapy was given subsequently. One year
      later, a recurrent episode of dactylitis responded promptly to the same regimen.
      Maintenance therapy was given, and no further recurrences were noted during the
      four-year follow-up. Sarcoid bone lesions are uncommon and arise selectively in
      the small bones of the hands and feet. Involvement of the calcaneus is
      exceedingly rare, and its treatment is not standardized. In our patient,
      glucocorticoid therapy combined with methotrexate and hydroxychloroquine were
      effective in controlling the disease.

PMID- 11324936
TI  - Ischiatic tuberculous osteitis and prolonged fever in a dialysis patient.

PMID- 11324937
TI  - Popliteal artery aneurysm resembling popliteal cyst: a case report.

PMID- 11324938
TI  - Reports of equivalence trials should not mask negative or mediocre results.

PMID- 11324939
TI  - Seymour S. Kety MD: the man and his accomplishments. Summary of a symposium in
      his honor at the VIIIth World Congress of Psychiatric Genetics, Versailles,
      France, 30 August 2000.
AB  - Seymour S. Kety was a physician and neuroscientist of great distinction. His
      impact on both the dynamics and imaging of cerebral blood flow and metabolism, as
      well as the nature-nurture controversy about the etiology of schizophrenia, led
      to his receiving the Lasker Award in 1999. He died at the age of 84 in the year
      2000, leaving medical research, and psychiatric genetics in particular, a
      bountiful legacy of rich science, thoughtful critiques and prophesies about
      hypotheses from the past and well into the future. Reviewed in this paper is a
      tribute to his work as presented during the VIIIth World Congress of Psychiatric
      Genetics in Versailles, France, August 2000.

PMID- 11324940
TI  - Gender differences in association between serotonin transporter gene polymorphism
      and personality traits.
AB  - Since Lesch and colleagues reported an association between anxiety-related traits
      (Neuroticism) and a functional polymorphism in the serotonin transporter gene
      regulatory region (5-HTTLPR), there have been several reports on 5-HTTLPR and
      personality traits with both positive and negative results. The present study was
      a further attempt to replicate the original findings of Lesch et al. in a
      population of well-defined normal healthy subjects. In addition, a variable
      number tandem repeat polymorphism in the second intron was included in this study
      because it has recently been shown to act as a transcriptional regulator.
      Personality traits were evaluated in 186 unrelated normal subjects by the NEO
      Five Factor Inventory. The most important and novel finding of this study was a
      significant association of mean Neuroticism scores with the short allele of 5
      HTTLPR in male subjects (t = 2.4, P = 0.018). We were thus able to replicate the
      finding of Lesch et al. of an association between serotonin transporter gene
      polymorphism (5-HTTLPR) and Neuroticism, but only in a male population. We also
      found a significant effect of gender on mean scores of Neuroticism [F = 3.9,
      degrees of freedom (df) = 1, 180, P = 0.05] and Agreeableness (F = 6.8, df = 1,
      180, P = 0.01), but no significant effect of 5-HTTLPR genotype on Neuroticism (F
      = 0.87, df= 2, 180, P = 0.42) or Agreeableness (F = 0.35, df = 2, 180, P = 0.7).
      These findings suggest that gender differences exist in contribution of genetic
      factors to behavioural phenotypes. They may also explain the inconsistencies in
      previous reports on association of Neuroticism with 5-HTTLPR from studies using
      different proportions of male and female subjects.

PMID- 11324941
TI  - Polymorphisms of tryptophan hydroxylase gene and the symptomatology of
      schizophrenia: an association study.
AB  - Serotonergic neurotransmission may be involved in the etiology of schizophrenia.
      We systematically searched for human tryptophan hydroxylase (TPH) coding
      polymorphisms, and detected a novel pentanucleotide repeat deletion polymorphism
      (GTTTT)4/5 in TPH intron 1b. We also confirmed A779C intron 7. Neither
      polymorphism showed a significant association with schizophrenia (182 patients
      with schizophrenia, 148 controls). A significant association, however, between
      A779C genotypes and the total Manchester Scale (MS) scores was found in male
      patients (P = 0.045). Subsequently, a significant association was also found
      between A779C genotypes and the MS negative symptoms scores in male patients (P =
      0.030). These results suggest that the TPH gene may play a role in the negative
      symptoms in male patients with schizophrenia.

PMID- 11324942
TI  - Comparative sequencing of the human CB1 cannabinoid receptor gene coding exon: no
      structural mutations in individuals exhibiting extreme responses to cannabis.
AB  - Rare but striking individual differences in responsiveness to cannabinoids have
      been observed that might involve mutations in the gene encoding the brain
      expressed cannabinoid receptor. In a preliminary study, the human CB1 cannabinoid
      receptor coding region was comparatively sequenced in different groups of
      individuals: one group showed acute psychotic symptoms after cannabis intake,
      while another group did not develop any psychopathology after long-term heavy
      cannabis abuse. No evidence for structural mutations was obtained, which might
      provide some insight into the molecular basis of individually different
      responsiveness to cannabinoids. Comparison of CB1 cannabinoid receptor amino acid
      sequences between species substantiated evidence that the protein sequence is
      relatively well conserved.

PMID- 11324943
TI  - A rare short allele of the serotonin transporter promoter region (5-HTTLPR) found
      in an aggressive schizophrenic patient of Jewish Libyan origin.
AB  - The serotonin transporter gene (SLC6A4), which plays a key role in the
      serotonergic pathway in the brain, is a candidate for mediating genetic
      susceptibility to various psychiatric disorders. There are two predominant
      alleles in the polymorphic promotor region [5-HT transporter gene-linked
      polymorphic region (5-HTTLPR)] of this gene: a long and a short allele with 16
      and 14 repeat units, respectively. The short allele has lower activity and is
      associated with several psychiatric disorders and personality traits. We
      identified and sequenced a novel allele with 13 repeat units, 23 base pairs
      shorter than the common short allele. This unique allele was detected in a
      schizophrenic patient of Jewish Libyan origin. The patient exhibited extreme
      aggressive behavior and committed suicide after several attempts. The novel short
      allele was not detected in 172 healthy control subjects and 361 patients with
      various mental disorders. The presence of a very short unique allele in a
      severely aggressive schizophrenic patient may reflect a specific effect on the
      particular phenotype, although it is unlikely that this allele has a major
      contribution to susceptibility to schizophrenia. The role of the allele in
      serotonin transport and possible association with disease phenotype should be
      further investigated.

PMID- 11324944
TI  - The DRD4 gene and the spiritual transcendence scale of the character temperament
      index.
AB  - Two hundred male subjects (81 college students and 119 subjects from an addiction
      treatment unit) were administered the Temperament and Character Inventory (TCI)
      and genotyped at the 48 base pair repeat polymorphism of the DRD4 gene. Subjects
      were divided by genotype into those carrying any < 4 repeat allele, those
      homozygous for the 4 repeat allele, and those with any > 4 repeat allele. The
      total MANCOVA of seven TCI summary scores, with age and diagnostic group as
      covariates, was significant (P < or = 0.001). The largest effect was with self
      transcendence (P < or = 0.001). The total MANCOVA for the three self
      transcendence subscores was significant (P < or = 0.017), with the spiritual
      acceptance subscore showing the most effect (P < or = 0.001, power = 0.91). These
      results suggest the DRD4 gene may play a role in the personality trait of
      spiritual acceptance. This may be a function of the high concentration of the
      dopamine D4 receptor in the cortical areas, especially the frontal cortex.

PMID- 11324945
TI  - Exonic variants of the GABA(B) receptor gene and panic disorder.
AB  - The enhancement of GABAergic neurotransmission has been closely linked to
      antipanic drug efficacy. This is the first study to investigate a putative
      association of exonic sequence variants of the human GABA(B) receptor 1
      (GABA(B)R1) gene and susceptibility to panic disorder. Three DNA sequence
      variants in exons 1a1, 7 and 11 were assessed by polymerase chain reaction-based
      restriction fragment length polymorphism in a case-control study among patients
      with panic disorder with and without agoraphobia (DSM III-R criteria) and blood
      donors. There was no indication of an increased vulnerability to panic disorder
      or agoraphobia with respect to the allelic variants under study.

PMID- 11324946
TI  - Tumour necrosis factor alpha and bipolar affective puerperal psychosis.
AB  - The macrophage theory of depression proposes that an excessive secretion of
      monocyte/macrophage cytokines causes symptoms of depression. It has been
      suggested that changes in immune function that accompany pregnancy and childbirth
      could contribute to the affective symptoms suffered by many puerperal women.
      Tumour necrosis factor alpha (TNFalpha) is a pro-inflammatory cytokine that has
      been implicated in inflammatory infections and immune diseases. Production of
      TNFalpha has been shown to be regulated by oestrogen, which suggests it as a
      potential candidate for susceptibility to post-partum mood disorders. Several
      polymorphisms have been identified in the TNFalpha gene. The -308 promoter
      polymorphism has been associated with elevated production of TNFalpha and has
      been found to influence the neurological outcome of various infections. In a case
      control association study, we have examined the frequency of this polymorphism in
      groups of parous DSM-IV Bipolar females with (N = 116) and without (N = 56)
      puerperal psychosis, and a female non-psychiatric comparison group (N = 72). We
      provided no support for the hypothesis that this polymorphism influences
      susceptibility to bipolar disorder, or acts as a trigger for puerperal psychosis.
      However, variation at other polymorphisms within TNFalpha or in other oestrogen
      regulated genes involved in immune function remain interesting candidates for
      study in post-partum mood disorders.

PMID- 11324947
TI  - New experimental apparatus for multimodal resonance imaging: initial EPRI and
      NMRI experimental results.
AB  - Electron paramagnetic resonance imaging (EPRI) is a recently developed imaging
      technique employed in the study of free radicals in living systems. A full
      understanding of many physiological and pathological processes involving free
      radicals has not yet been attempted. The reason for this is that whilst nuclear
      magnetic resonance imaging (NMRI) is able to generate very accurate images of
      soft tissues and organs, EPRI does not have this capability because of its
      sensitivity limitations and the large linewidths of paramagnetic probes. This
      work describes the development and optimization of a multimodal apparatus capable
      of performing both pulsed EPRI and NMRI experiments on the same sample. The
      instrument combines the possibilities offered by both techniques: the functional
      and biochemical information achieved with EPRI, and the high-resolution
      anatomical images generated by NMRI. At present, these experiments are performed
      by moving the sample from an EPRI spectrometer to an NMRI apparatus.
      Consequently, the acquisition times are very long and several problems arise in
      image reconstruction. On the other hand, a unique apparatus operating in the two
      modalities greatly reduces the acquisition times and makes it possible to relate
      accurately the observed distribution of electron spin density with the anatomical
      description of individual organs. The experiments are performed at 357 Gauss,
      corresponding to a resonance frequency of 1.52 MHz for NMR and 1 GHz for EPR. In
      the present work, a detailed description of the apparatus is reported, including
      the main magnet, the gradient assembly, the multimodal cavity and the transmitter
      and receiver systems. The preliminary experimental results obtained by this
      apparatus are presented.

PMID- 11324948
TI  - Quasistatic zooming for regional hyperthermia treatment planning.
AB  - Due to current computer limitations, specific absorption rate (SAR) distributions
      in regional hyperthermia treatment planning (HTP) are limited to centimetre
      resolution. However, since patient anatomy is highly structured on a millimetre
      scale, millimetre-resolution SAR modelling is required. A method called
      quasistatic zooming has been developed to obtain a high-resolution SAR
      distribution within a volume of interest (VOI): using the low-resolution E-field
      distribution and the high-resolution patient anatomy, the high-resolution SAR
      distribution is computed within a small zoom volume Q (small compared with the
      wavelength in water (lambda(w))). Repeating this procedure yields the zoomed
      resolution SAR distribution in an arbitrary VOI. To validate this method for a
      VOI that is not small compared with lambda(w), high-resolution finite-difference
      time-domain (FDTD) modelling is needed. Since this is impractical for a clinical
      applicator, a computer model of a small applicator has been created. A partial
      patient anatomy is inserted into the applicator and both high- and low-resolution
      SAR distributions are computed for this geometry. For the same geometry, zoomed
      resolution SAR distributions are computed with different sizes of Q. To compare
      the low- and zoomed-resolution SAR distributions with the high-resolution one,
      the correlation and averaged absolute difference are computed. These numbers are
      improved considerably using zooming (correlation 58% to 92%; averaged absolute
      difference 43% to 20%). These results appear to be independent of the size of Q,
      up to 0.3 lambda(w). Quasistatic zooming is a valuable tool in high-resolution
      regional HTP.

PMID- 11324949
TI  - Point dose calculations using an analytical pencil beam kernel for IMRT plan
      checking.
AB  - A method to verify the monitor units for a treatment plan is to calculate point
      doses, possibly at the isocentre, by using a simple calculation method. This
      verification is recommended to find mistakes in the treatment plan. Treatment
      plans for intensity modulated radiation therapy are no exception. The method
      should employ a simple physical model and a dose calculation algorithm, which is
      different from the method used for the treatment plan. Our approach uses a
      convolution algorithm and an analytical pencil beam kernel with eight parameters.
      The model is intuitive and simple. At the same time, the method is so general
      that it can be applied to both step-and-shoot and sliding-window techniques. The
      results of applications to actual treatment plans show that the calculated total
      isocentre doses are accurate within +/-2% of planned doses for six-field prostate
      plans when calculation points are in a uniform dose region. Head and neck cases
      show a slightly larger difference than prostate cases. When calculation points
      are located in a region of high dose gradient, however, the difference could be
      greater than 5%.

PMID- 11324950
TI  - The MLC tongue-and-groove effect on IMRT dose distributions.
AB  - We have investigated the tongue-and-groove effect on the IMRT dose distributions
      for a Varian MLC. We have compared the dose distributions calculated using the
      intensity maps with and without the tongue-and-groove effect. Our results showed
      that, for one intensity-modulated treatment field, the maximum tongue-and-groove
      effect could be up to 10% of the maximum dose in the dose distributions. For an
      IMRT treatment with multiple gantry angles (> or = 5), the difference between the
      dose distributions with and without the tongue-and-groove effect was hardly
      visible, less than 1.6% for the two typical clinical cases studied. After
      considering the patient setup errors, the dose distributions were smoothed with
      reduced and insignificant differences between plans with and without the tongue
      and-groove effect. Therefore, for a multiple-field IMRT plan (> or = 5), the
      tongue-and-groove effect on the IMRT dose distributions will be generally
      clinically insignificant due to the smearing effect of individual fields. The
      tongue-and-groove effect on an IMRT plan with small number of fields (< 5) will
      vary depending on the number of fields in a plan (coplanar or non-coplanar), the
      MLC leaf sequences and the patient setup uncertainty, and may be significant (>
      5% of maximum dose) in some cases, especially when the patient setup uncertainty
      is small (< or = 2 mm).

PMID- 11324951
TI  - The relationship between radiation-induced chemical processes and transverse
      relaxation times in polymer gel dosimeters.
AB  - The effects of ionizing radiation in different compositions of polymer gel
      dosimeters are investigated using FT-Raman spectroscopy and NMR T2 relaxation
      times. The dosimeters are manufactured from different concentrations of
      comonomers (acrylamide and N,N'-methylene-bis-acrylamide) dispersed in different
      concentrations of an aqueous gelatin matrix. Results are analysed using a model
      of fast exchange of magnetization between three proton pools. The fraction of
      protons in each pool is determined using the known chemical composition of the
      dosimeter and FT-Raman spectroscopy. Based on these results, the physical and
      chemical processes in interplay in the dosimeters are examined in view of their
      effect on the changes in T2. The precipitation of growing macroradicals and the
      scavenging of free radicals by gelatin are used to explain the rate of
      polymerization. The model describes the changes in T2 as a function of the
      absorbed dose up to 50 Gy for the different compositions. This is expected to aid
      the theoretical design of new, more efficient dosimeters, since it was
      demonstrated that the optimum dosimeter (i.e, with the lowest dose resolution)
      must have a range of relaxation times which match the range of T2 values which
      can be determined with the lowest uncertainty using an MRI scanner.

PMID- 11324952
TI  - Manual calculation of treatment time for high dose rate brachytherapy with a
      flexible intraoperative template (FIT).
AB  - A method is presented for estimating the total treatment time for a brachytherapy
      radiation fraction with a planar flexible intraoperative template (FIT), using an
      192Ir high dose rate afterloading device. The FIT can be rectangular or
      irregularly shaped. The manual calculation serves as an independent check of the
      treatment time calculated by the treatment planning system for applications with
      varying sizes, shapes and dose prescription depths. The parameters required for
      the calculation are the number of active dwell positions, the catheter spacing
      and dwell position spacing, the source strength, the applied dose and the depth
      of dose prescription. For a fixed depth of dose prescription (1.25 cm) and fixed
      dwell position and catheter spacing (0.5 and 1 cm respectively) the manual
      calculation accurately predicts (usually within 2%) the total treatment time as
      calculated by the treatment planning system. For varying catheter and dwell
      position spacings and dose prescription depths the accuracy is still within 7%.
      An action threshold of 5% allows detection of errors made in the number of active
      dwell positions (+/-9), catheter spacing (+/-1 mm) and dose prescription depth
      (+/-1 mm). Errors in dwell position spacing (0.25 cm or more) could also be
      accurately detected.

PMID- 11324954
TI  - Treatment planning for heavy ion radiotherapy: clinical implementation and
      application.
AB  - The clinical implementation and application of a novel treatment planning system
      (TPS) for scanned ion beams is described, which is in clinical use for carbon ion
      treatments at the German heavy ion facility (GSI). All treatment plans are
      evaluated on the basis of biologically effective dose distributions. For therapy
      control, in-beam positron emission tomography (PET) and an online monitoring
      system for the beam intensity and position are used. The absence of a gantry
      restricts the treatment plans to horizontal beams. Most of the treatment plans
      consist of two nearly opposing lateral fields or sometimes orthogonal fields. In
      only a very few cases a single beam was used. For patients with very complex
      target volumes lateral and even distal field patching techniques were applied.
      Additional improvements can be achieved when the patient's head is fixed in a
      tilted position, in order to achieve sparing of the organs at risk. In order to
      test the stability of dose distributions in the case of patient misalignments we
      routinely simulate the effects of misalignments for patients with critical
      structures next to the target volume. The uncertainties in the range calculation
      are taken into account by a margin around the target volume of typically 2-3 mm,
      which can, however, be extended if the simulation demonstrates larger deviations.
      The novel TPS developed for scanned ion beams was introduced into clinical
      routine in December 1997 and was used for the treatment planning of 63 patients
      with head and neck tumours until July 2000. Planning strategies and methods were
      developed for this tumour location that facilitate the treatment of a larger
      number of patients with the scanned heavy ion beam in a clinical setting. Further
      developments aim towards a simultaneous optimization of the treatment field
      intensities and more effective procedures for the patient set-up. The results
      demonstrate that ion beams can be integrated into a clinical environment for
      treatment planning and delivery.

PMID- 11324953
TI  - An optimization method for importance factors and beam weights based on genetic
      algorithms for radiotherapy treatment planning.
AB  - We propose a new method for selecting importance factors (for regions of interest
      like organs at risk) used to plan conformal radiotherapy. Importance factors,
      also known as weighting factors or penalty factors, are essential in determining
      the relative importance of multiple objectives or the penalty ratios of
      constraints incorporated into cost functions, especially in dealing with dose
      optimization in radiotherapy treatment planning. Researchers usually choose
      importance factors on the basis of a trial-and-error process to reach a balance
      between all the objectives. In this study, we used a genetic algorithm and
      adopted a real-number encoding method to represent both beam weights and
      importance factors in each chromosome. The algorithm starts by optimizing the
      beam weights for a fixed number of iterations then modifying the importance
      factors for another fixed number of iterations. During the first phase, the
      genetic operators, such as crossover and mutation, are carried out only on beam
      weights, and importance factors for each chromosome are not changed or 'frozen'.
      In the second phase, the situation is reversed: the beam weights are 'frozen' and
      the importance factors are changed after crossover and mutation. Through
      alternation of these two phases, both beam weights and importance factors are
      adjusted according to a fitness function that describes the conformity of dose
      distribution in planning target volume and dose-tolerance constraints in organs
      at risk. Those chromosomes with better fitness are passed into the next
      generation, showing that they have a better combination of beam weights and
      importance factors. Although the ranges of the importance factors should be set
      in advance by using this algorithm, it is much more convenient than selecting
      specific numbers for importance factors. Three clinical examples are presented
      and compared with manual plans to verify this method. Three-dimensional standard
      displays and dose-volume histograms are shown to demonstrate that this method is
      feasible, automatic and convenient.

PMID- 11324955
TI  - Time resolved optical tomography of the human forearm.
AB  - A 32-channel time-resolved optical imaging instrument has been developed
      principally to study functional parameters of the new-born infant brain. As a
      prelude to studies on infants, the device and image reconstruction methodology
      have been evaluated on the adult human forearm. Cross-sectional images were
      generated using time-resolved measurements of transmitted light at two
      wavelengths. All data were acquired using a fully automated computer-controlled
      protocol. Images representing the internal scattering and absorbing properties of
      the arm are presented, as well as images that reveal physiological changes during
      a simple finger flexion exercise. The results presented in this paper represent
      the first simultaneous tomographic reconstruction of the internal scattering and
      absorbing properties of a clinical subject using purely temporal data, with
      additional co-registered difference images showing repeatable absorption changes
      at two wavelengths in response to exercise.

PMID- 11324956
TI  - The value of the LA48 linear ion chamber array for characterization of intensity
      modulated beams.
AB  - In this paper the performance of the LA48 linear ion chamber array (PTW,
      Freiburg, Germany) for characterization of intensity-modulated (IM) beams was
      investigated. First, some elementary properties were explored. A series of beam
      penumbras and output factors for small rectangular fields were measured at 6 and
      18 MV, and the results were compared with data obtained using a diamond detector.
      The energy and dose rate dependence of the array response were examined, and the
      leakage current was assessed. In a second step, profiles were measured for two
      clinically delivered IM beams and for a dynamic wedge. The interplay between the
      sharpening of the penumbra by the upper metal electrode plate of the array and
      the volume averaging of the 4 x 4 mm ion chamber elements results in precise
      measurements, even in regions of high dose gradient. It is true, however, that
      the metal electrodes imply a small energy spectrum dependence in the array
      response. The dose rate dependence is found to be negligible. All of this makes,
      the LA48 linear array a suitable device for analysing dose distributions of
      clinical IM beams.

PMID- 11324957
TI  - Radionuclide therapy with bone-seeking compounds: Monte Carlo calculations of
      dose-volume histograms for bone marrow in trabecular bone.
AB  - The purpose of the present work was to investigate how haematopoietic stem cell
      survival is affected by the differences in the dose distribution that arise from
      different radionuclides contained in bone-seeking radiopharmaceuticals. This was
      carried out in three steps: (a) calculations of representative dose distributions
      in individual bone marrow cavities that are irradiated by sources of 89Sr, 186Re,
      117mSn or 153Sm, uniformly distributed on the bone surfaces; (b) assessment of
      the corresponding haematopoietic stem cell survival and (c) a comparison of these
      results with results obtained using the assumption of a uniform dose
      distribution. Two different idealized models of the geometry of trabecular bone
      were formulated, each consisting of an infinite array of identical elements.
      Monte Carlo simulations were used to generate dose-volume histograms that were
      used to assess haematopoietic stem cell survival with two different assumptions
      about spatial cell distributions. Compared with a homogeneous dose distribution,
      the estimated cell survival was markedly higher for 117mSn and 153Sm, and only
      slightly different for 89Sr and 186Re. The quantitative results differed between
      the two geometric models and the assumptions about spatial cell distribution, but
      the trends were the same. The results imply that it is necessary to include dose
      distributions for individual bone marrow cavities in considerations concerning
      bone marrow toxicity.

PMID- 11324958
TI  - Monte Carlo simulation of electron beams from an accelerator head using PENELOPE.
AB  - The Monte Carlo code PENELOPE has been used to simulate electron beams from a
      Siemens Mevatron KDS linac with nominal energies of 6, 12 and 18 MeV. Owing to
      its accuracy, which stems from that of the underlying physical interaction
      models, PENELOPE is suitable for simulating problems of interest to the medical
      physics community. It includes a geometry package that allows the definition of
      complex quadric geometries, such as those of irradiation instruments, in a
      straightforward manner. Dose distributions in water simulated with PENELOPE agree
      well with experimental measurements using a silicon detector and a monitoring
      ionization chamber. Insertion of a lead slab in the incident beam at the surface
      of the water phantom produces sharp variations in the dose distributions, which
      are correctly reproduced by the simulation code. Results from PENELOPE are also
      compared with those of equivalent simulations with the EGS4-based user codes BEAM
      and DOSXYZ. Angular and energy distributions of electrons and photons in the
      phase-space plane (at the downstream end of the applicator) obtained from both
      simulation codes are similar, although significant differences do appear in some
      cases. These differences, however, are shown to have a negligible effect on the
      calculated dose distributions. Various practical aspects of the simulations, such
      as the calculation of statistical uncertainties and the effect of the 'latent'
      variance in the phase-space file, are discussed in detail.

PMID- 11324959
TI  - Experimental p(wall) and p(cel) correction factors for ionization chambers in low
      energy clinical proton beams.
AB  - Current dosimetry protocols for clinical protons using ionization chambers do not
      take into account ionization chamber-dependent perturbation correction factors.
      In the present investigation, the relative response of 17 cylindrical ionization
      chambers was evaluated at three proton beam qualities: at two points in a
      modulated beam and one point in a non-modulated beam, all with an incident energy
      of 75 MeV. Thirteen of the ionization chambers had a Farmer-type geometry but
      consisted of different combinations of wall and central electrode materials. All
      ionization chambers were calibrated in terms of air kerma as well as in terms of
      absorbed dose to water in a 60Co beam. The relative response of the ionization
      chambers was compared with results of Monte Carlo simulations of proton and
      secondary electron transport in the phantom and the ionization chamber geometry.
      The results of the measurements for cylindrical ionization chambers show relative
      perturbation effects that are limited to 0.5-1%, resulting in perturbation
      correction factors that are larger than unity compared with an NE2571 ionization
      chamber. The experimental relative wall and total perturbation correction factors
      agree with Monte Carlo calculated values, indicating that the differences between
      the responses of different ionization chambers are due to secondary electron
      effects. This conclusion is supported by the comparison of our results with those
      from other investigators after re-analysis of their data. The central electrode
      perturbation correction factor for an aluminium electrode in a Farmer-type
      geometry was found to be unity within the experimental uncertainties.

PMID- 11324960
TI  - Reconsideration of the backscatter components in the intermediate cavity theory
      for photon beams.
AB  - Cavity theories are used to relate the dose in a medium to the dose in a cavity.
      No satisfactory analytical approach exists for the case of intermediate cavities,
      such as TLDs, when interface effects are important. Burlin proposed a general
      cavity theory that accounts for the cavity size but which ignores interface
      effects between cavity material and the surrounding materials. Horowitz modified
      Burlin's theory to include a more systematic account for the contribution of
      electrons generated in the cavity. Both Kearsley and Haider proposed new models
      that consider backscattering effects at cavity interfaces. However, these last
      models introduce additional parameters whose values are not easily available. By
      using a pure analytical approach, higher orders of backscatter terms were
      considered and a photon cavity expression was derived. The proposed formula
      depends on backscattering and attenuation coefficients of the cavity material and
      the surrounding media as well as the size of the cavity and angular effects. This
      expression has the Burlin and Bragg-Gray formulae as limiting cases and follows
      better the pattern of Ogunleye's experimental results.

PMID- 11324961
TI  - Feasibility of automatic marker detection with an a-Si flat-panel imager.
AB  - Here we study automatic detection of implanted gold markers relative to the field
      boundary in portal images for on-line position verification. Portal images
      containing 1-2 MU were taken with an amorphous silicon flat-panel imager. The
      images were obtained with lateral field at 18 MV. Both the detection success rate
      and the localization accuracy of markers of 1.0 and 1.2 mm diameter were
      determined with the help of a marker detection method based on a marker
      extraction kernel. A method for determining a fiducial reference point related to
      the field boundary was developed. Detection success rates were 0.99, 0.90 and
      0.95 for markers of 1.2 mm diameter and 5 mm length, 1.0 mm diameter and 5 mm
      length and 1.0 mm diameter and 10 mm length respectively. The localization
      accuracy appeared to be better than 0.3 mm. The reference point could be
      reproduced with an accuracy equal to 1 pixel (0.5 mm at isocentre) within one
      fraction. During the first few seconds of a treatment fraction the field edge was
      not stable, which appeared to be an effect of the motion of the radiation source.
      Thanks to the use an a-Si flat-panel imager, on-line position verification using
      implanted gold markers becomes clinically feasible. We can use a clinically
      acceptable marker diameter as small as 1.0 mm. These markers can be automatically
      detected in portal images obtained with 1-2 MU relative to a stable reference
      point related to the field boundary.

PMID- 11324962
TI  - Non-invasive determination of muscle blood flow in the extremities from laser
      Doppler spectra.
AB  - We investigate theoretically the non-invasive determination of blood flow in
      muscles of the extremities using laser Doppler measurements. Laser Doppler
      spectra are calculated using Monte Carlo simulations and solutions of the
      correlation diffusion equation. The extremities are modelled as a two-layered
      turbid medium. The first layer represents the skin and subcutaneous fat layer and
      the second layer the muscle. It is shown that the absolute root-mean-square
      velocity of the blood in the muscle layer can be accurately derived in many
      practical cases if the laser Doppler spectra are measured at a distance which is
      sufficiently far from the source, and if the optical properties of the muscle are
      simultaneously determined.

PMID- 11324963
TI  - Mechanical haemolysis in shock wave lithotripsy (SWL): II. In vitro cell lysis
      due to shear.
AB  - In this work we report injury to isolated red blood cells (RBCs) due to focused
      shock waves in a cavitation-free environment. The lithotripter-generated shock
      wave was refocused by a parabolic reflector. This refocused wave field had a
      tighter focus (smaller beam width and a higher amplitude) than the lithotripter
      wave field, as characterized by a membrane hydrophone. Cavitation was eliminated
      by applying overpressure to the fluid. A novel passive cavitation detector (HP
      PCD) operating at high overpressure (up to 7 MPa) was used to measure acoustic
      emission due to bubble activity. The typical 'double-bang' emission measured in
      the lithotripter free-field was replaced by a continuum of weak signals when the
      fluid was enclosed in a pressure chamber. No acoustic emissions were measured
      above an overpressure of 5.5 MPa. Aluminium foils were used to study shock wave
      damage and had distinct deformation features corresponding to exposure
      conditions, i.e. pitting and denting accompanied by wrinkling. Pitting was
      eliminated by high overpressure and so was due to cavitation bubble collapse,
      whereas denting and wrinkling were caused by the reflected shock wave refocused
      by the parabolic reflector. RBCs suspended in phosphate-buffered saline (PBS)
      were exposed to the reflected wave field from a parabolic reflector and also from
      a flat reflector. Exposure to the wave field from the parabolic reflector
      increased haemolysis four-fold compared with untreated controls and was twice
      that of cell lysis with the flat reflector. Recently we analysed deformation and
      rupture of RBCs when subjected to a flow field set up by a focused shock. The
      cell lysis results presented here are in qualitative agreement with our
      theoretical prediction that haemolysis is directly related to the gradient of
      shock strength and validates shearing as a cell lysis mechanism in SWL.

PMID- 11324964
TI  - Rapidly recomputable EEG forward models for realistic head shapes.
AB  - With the increasing availability of surface extraction techniques for magnetic
      resonance and x-ray computed tomography images, realistic head models can be
      readily generated as forward models in the analysis of electroencephalography
      (EEG) and magnetoencephalography (MEG) data. Inverse analysis of this data,
      however, requires that the forward model be computationally efficient. We propose
      two methods for approximating the EEG forward model using realistic head shapes.
      The 'sensor-fitted sphere' approach fits a multilayer sphere individually to each
      sensor, and the 'three-dimensional interpolation' scheme interpolates using a
      grid on which a numerical boundary element method (BEM) solution has been
      precomputed. We have characterized the performance of each method in terms of
      magnitude and subspace error metrics, as well as computational and memory
      requirements. We have also made direct performance comparisons with traditional
      spherical models. The approximation provided by the interpolative scheme had an
      accuracy nearly identical to full BEM, even within 3 mm of the inner skull
      surface. Forward model computation during inverse procedures was approximately 30
      times faster than for a traditional three-shell spherical model. Cast in this
      framework, high-fidelity numerical solutions currently viewed as computationally
      prohibitive for solving the inverse problem (e.g. linear Galerkin BEM) can be
      rapidly recomputed in a highly efficient manner. The sensor-fitting method has a
      similar one-time cost to the BEM method, and while it produces some improvement
      over a standard three-shell sphere, its performance does not approach that of the
      interpolation method. In both methods, there is a one-time cost associated with
      precomputing the forward solution over a set of grid points.

PMID- 11324965
TI  - Receptor dose in digital fluorography: a comparison between theory and practice.
AB  - A method of identifying the dose per image when quantum mottle no longer
      dominates the image statistics is presented as a first step towards quantitative
      optimization in native and subtracted digital fluorography. The method is based
      on measurements of threshold contrast over a range of receptor doses and the
      application of a simple model of the threshold contrast detection task to
      estimate the magnitude of system noise sources. The point at which system and
      quantum noise sources are equal in magnitude is proposed as the practical upper
      limit for dose per image. The method is applied to a typical digital fluorography
      system and the results are placed into the context of the range of dose per image
      values found from a regional survey of digital fluorography units. While there is
      broad agreement between the dose per image values in the survey with values
      predicted from the experimental method, the considerable spread in survey doses
      suggests there are instances where the use of a high dose per image is
      unjustified.

PMID- 11324966
TI  - Non-rigid image registration using a median-filtered coarse-to-fine displacement
      field and a symmetric correlation ratio.
AB  - Conventional approaches to image registration are generally limited to image-wide
      rigid transformations. However, the body and its internal organs are non-rigid
      structures that change shape due to changes in the body's posture during image
      acquisition, and due to normal, pathological and treatment-related variations.
      Inter-subject matching also constitutes a non-rigid registration problem. In this
      paper, we present a fully automated non-rigid image registration method that
      maximizes a local voxel-based similarity metric. Overlapping image blocks are
      defined on a 3D grid. The transformation vector field representing image
      deformation is found by translating each block so as to maximize the local
      similarity measure. The resulting sparsely sampled vector field is median
      filtered and interpolated by a Gaussian function to ensure a locally smooth
      transformation. A hierarchical strategy is adopted to progressively establish
      local registration associated with image structures at diminishing scale.
      Simulation studies were carried out to evaluate the proposed algorithm and to
      determine the robustness of various voxel-based cost functions. Mutual
      information, normalized mutual information, correlation ratio (CR) and a new
      symmetric version of CR were evaluated and compared. A T1-weighted magnetic
      resonance (MR) image was used to test intra-modality registration. Proton density
      and T2-weighted MR images of the same subject were used to evaluate inter
      modality registration. The proposed algorithm was tested on the 2D MR images
      distorted by known deformations and 3D images simulating inter-subject
      distortions. We studied the robustness of cost functions with respect to image
      sampling. Results indicate that the symmetric CR gives comparable registration to
      mutual information in intra- and inter-modality tasks at full sampling and is
      superior to mutual information in registering sparsely sampled images.

PMID- 11324967
TI  - An automated segmentation method for three-dimensional carotid ultrasound images.
AB  - We have developed an automated segmentation method for three-dimensional vascular
      ultrasound images. The method consists of two steps: an automated initial contour
      identification, followed by application of a geometrically deformable model
      (GDM). The formation of the initial contours requires the input of a single seed
      point by the user, and was shown to be insensitive to the placement of the seed
      within a structure. The GDM minimizes contour energy, providing a smoothed final
      result. It requires only three simple parameters, all with easily selectable
      values. The algorithm is fast, performing segmentation on a 336 x 352 x 200
      volume in 25 s when running on a 100 MHz 9500 Power Macintosh prototype. The
      segmentation algorithm was tested on stenosed vessel phantoms with known
      geometry, and the segmentation of the cross-sectional areas was found to be
      within 3% of the true area. The algorithm was also applied to two sets of patient
      carotid images, one acquired with a mechanical scanner and the other with a
      freehand scanning system, with good results on both.

PMID- 11324968
TI  - Specific absorbed fractions from the image-based VIP-Man body model and EGS4-VLSI
      Monte Carlo code: internal electron emitters.
AB  - VIP-Man is a whole-body anatomical model newly developed at Rensselaer from the
      high-resolution colour images of the National Library of Medicine's Visible Human
      Project. This paper summarizes the use of VIP-Man and the Monte Carlo method to
      calculate specific absorbed fractions from internal electron emitters. A
      specially designed EGS4 user code, named EGS4-VLSI, was developed to use the
      extremely large number of image data contained in the VIP-Man. Monoenergetic and
      isotropic electron emitters with energies from 100 keV to 4 MeV are considered to
      be uniformly distributed in 26 organs. This paper presents, for the first time,
      results of internal electron exposures based on a realistic whole-body
      tomographic model. Because VIP-Man has many organs and tissues that were
      previously not well defined (or not available) in other models, the efforts at
      Rensselaer and elsewhere bring an unprecedented opportunity to significantly
      improve the internal dosimetry.

PMID- 11324969
TI  - Monte Carlo dose calculations for dynamic IMRT treatments.
AB  - Dose calculations for intensity modulated radiation therapy (IMRT) face new
      challenges due to the complex leaf geometry and time dependent nature of the
      delivery. A fast method of particle transport through a dynamic multileaf
      collimator (MLC) geometry that accounts for photon attenuation and first
      scattered Compton photon production has been incorporated into an existing Monte
      Carlo code used for patient dose calculations. Dosimetric agreement between
      calculation and measurement for two photon energies and MLC types is within
      experimental error for the sliding window tests. For a patient IMRT field, the
      Monte Carlo calculations are closer to measured dose than similar superposition
      or pencil beam calculations.

PMID- 11324970
TI  - On the accuracy and effectiveness of dose reconstruction for tomotherapy.
AB  - Dose reconstruction is a process that re-creates the treatment-time dose
      deposited in a patient provided there is knowledge of the delivered energy
      fluence and the patient's anatomy at the time of treatment. A method for
      reconstructing dose is presented. The process starts with delivery verification,
      in which the incident energy fluence from a treatment is computed using the exit
      detector signal and a transfer matrix to convert the detector signal to energy
      fluence. With the verified energy fluence and a CT image of the patient in the
      treatment position, the treatment-time dose distribution is computed using any
      model-based algorithm such as convolution/superposition or Monte Carlo. The
      accuracy of dose reconstruction and the ability of the process to reveal delivery
      errors are presented. Regarding accuracy, a reconstructed dose distribution was
      compared with a measured film distribution for a simulated breast treatment
      carried out on a thorax phantom. It was found that the reconstructed dose
      distribution agreed well with the dose distribution measured using film: the
      majority of the voxels were within the low and high dose-gradient tolerances of
      3% and 3 mm respectively. Concerning delivery errors, it was found that errors
      associated with the accelerator, the multileaf collimator and patient positioning
      might be detected in the verified energy fluence and are readily apparent in the
      reconstructed dose. For the cases in which errors appear in the reconstructed
      dose, the possibility for adaptive radiotherapy is discussed.

PMID- 11324971
TI  - Curved optics for x-ray phase contrast imaging by synchrotron radiation.
AB  - Conventional radiographic techniques have strong limitations when low-absorption
      contrast samples are imaged. Phase contrast radiography has been shown to produce
      high-quality images of soft tissues. In this technique the recorded intensity
      patterns are related to gradients in the refractive index of the sample. A
      critical point of this new technique is the need to employ crystal analysers,
      which results in an appreciable reduction in the beam intensity and consequently
      in rather long exposure times. In this paper the use of focused beams is
      suggested to overcome this aspect. Biological samples with small structures and
      low absorption variations were imaged using both flat and curved monochromator
      crystals, demonstrating that the use of curved optics leads to a decrease in the
      exposure time with only a limited degradation of the spatial resolution. This
      opens up the possibility of using the phase contrast technique with laboratory
      sources.

PMID- 11324972
TI  - Beat-to-beat analysis method for magnetocardiographic recordings during
      interventions.
AB  - Multichannel magnetocardiography (MCG) during exercise testing has been shown to
      detect myocardial ischaemia in patients with coronary artery disease. Previous
      studies on exercise MCG have focused on one or few time intervals during the
      recovery period and only a fragment of the data available has been utilized. We
      present a method for beat-to-beat analysis and parametrization of the MCG signal.
      The method can be used for studying and quantifying the changes induced in the
      MCG by interventions. We test the method with data recorded in bicycle exercise
      testing in healthy volunteers and patients with coronary artery disease.
      Information in all cardiac cycles recorded during the recovery period of exercise
      MCG testing is, for the first time, utilized in the signal analysis. Exercise
      induced myocardial ischaemia was detected by heart rate adjustment of change in
      magnetic field map orientation. In addition to the ST segment, the T wave in the
      MCG was also found to provide information related to myocardial ischaemia. The
      method of analysis efficiently utilizes the spatial and temporal properties of
      multichannel MCG mapping, providing a new tool for detecting and quantifying fast
      phenomena during interventional MCG studies. The method can also be applied to an
      on-line analysis of MCG data.

PMID- 11324973
TI  - Monitoring of cell and tissue responses to photodynamic therapy by electrical
      impedance spectroscopy.
AB  - Electrical impedance spectroscopic (EIS) monitoring of photodynamic therapy (PDT)
      was investigated in vivo in rat liver and in vitro in multicellular spheroids.
      Liver impedance was continuously measured with two needle electrodes before,
      during and up to 3 hours following Photofrin-PDT. EIS spectra were altered
      immediately after PDT, with significant changes in conductivity at approximately
      10 kHz, and in permittivity at approximately 30 kHz and 1 MHz. The change in
      permittivity at high frequencies was related to oedema, while low-frequency
      effects were attributed to cell necrosis and vascular changes. Photofrin-PDT
      treated spheroids showed dose-dependent decreases in permittivity and
      conductivity at frequencies above 10 and 100 kHz, respectively. Histology showed
      concomitant development of a damaged rim containing sparsely distributed cells
      with compromised membranes and lightly staining cytoplasm. Different EIS
      responses to apoptotic versus necrotic modes of cell death further verified the
      sensitivity of impedance to purely cellular changes in the spheroid model. In
      conclusion, EIS sensitivity to PDT-induced damage, at both the cell and tissue
      level, varies with dose and time, and can be correlated qualitatively to
      biological changes.

PMID- 11324974
TI  - Laser thermal therapy: utility of interstitial fluence monitoring for locating
      optical sensors.
AB  - Multipoint optical fluence measurements can potentially be used to detect
      coagulation-induced changes in optical propagation during interstitial laser
      thermal therapy. Estimating the dimensions of coagulation using on-line optical
      monitoring, which is applicable to treatments where the tip of the source fibre
      is not precharred, may be limited by the accuracy of the placement of optical
      sensors with respect to source fibres. A strategy has been developed to determine
      accurately the position of a four-sensor linear array, prior to treatment, using
      optical fluence data obtained from the sensors for low-power (< or = 0.5 W)
      irradiation. A minimum of four sensors in an array was required in order to
      develop a mathematical formulation for position determination that did not
      require tissue optical properties or laser power as input. Optical propagation
      was based on diffusion theory for homogeneous tissues in spherical geometry. Low
      input laser power is needed to ensure that there are no thermally induced changes
      in tissue optical properties not accounted for in the mathematical description.
      Experimental evaluation was performed in a tissue-equivalent liquid phantom using
      0.5 W of 805 nm optical energy and a translatable isotropic optical sensor. For
      sensor locations with 2 mm spacing, placement accuracy of 0.67 mm was achieved.
      The accuracy improved to 0.13 mm as the sensor spacing increased to 5 mm.

PMID- 11324975
TI  - Spatial dependence of the phase in localized bioelectrical impedance analysis.
AB  - The variety of phase functions, theta(z) = arctan X(z)/R(z), observed earlier on
      the thighs of healthy and seriously ill subjects via localized bioelectrical
      impedance analysis, can be represented by a model which combines realistic thigh
      shapes with homogeneous, axially symmetric conductivity tensors. While
      quantitative results depend sensitively on the way current is injected, it
      appears to be generally true that d theta/d(z) < 0 whenever phi(r) > phi(z) (and
      vice versa), where phi(r) and phi(z) are the phases of the radial and
      longitudinal conductivity components.

PMID- 11324976
TI  - Tissue engineering: the biophysical background.
AB  - Tissue engineering is the construction, repair or replacement of damaged or
      missing tissue in humans and other animals. This engineering may take place
      within the animal body or as tissue constructs to be made in a bioreactor for
      later grafting into the animal. The minimal set of materials for this are the
      appropriate types of cell. Usually, however, non-living substrata are used as
      well. These substrata may be nothing more than materials that bulk up any voids
      in the damaged tissue and provide the mechanical strength that has been lost when
      the tissue is damaged or removed. They may serve a similar pair of functions in
      the bioreactor. They can do much more in terms of pattern formation. The
      orientations and morphology of the cells, the arrangement of intercellular
      material as it is laid down and the relationships between different cell types in
      the repairing or construct tissue are all of importance, for these should
      resemble the correct normal tissue as closely as possible. Most of these
      requirements are ones involving pattern formation. This review discusses the
      various ways in which tissue pattern can be engineered chiefly from a biophysical
      standpoint. Unpatterned cells are effectively not tissue. This engineering
      includes the use of topography on the substrata, chemical patterning of adhesive
      and other cues for the cells, mechanical force application to cause cell
      orientation and appropriate synthetic responses and electrical fields. The review
      also discusses the methods used to impart the appropriate cues to and through the
      materials which are often biodegradable polymers. The article gives particular
      attention to regions of research and practice where the involvement of the
      physicist or biophysicist is of importance.

PMID- 11324977
TI  - Impact of Mitomycin-C application time on the scleral Mitomycin-C concentration.
AB  - The aim of this study was to determine the effect of varying the application time
      of Mitomycin-C (MMC) on the scleral concentration of MMC. The sclerae of 14 human
      donor eyes were used for this study. The episcleral sides of the 4 scleral
      quadrants of each donor eye were exposed for 0.5, 1, 3 and 5 min to round, 8 mm
      diameter sponges soaked with 50 microl of 0.2 mg/ml MMC. After 40-ml irrigation
      with saline, a central 8-mm diameter scleral disk was punched out, homogenized
      and analyzed with high performance liquid chromatography (HPLC). The scleral MMC
      concentrations (microg/g) after 0.5, 1, 3 and 5 min application times were 6.40
      (+/-3.38), 9.02 (+/-2.40), 12.31 (+/-3.37), and 13.97 (+/-3.83). The differences
      of scleral MMC concentration in paired t-tests were statistically significant
      comparing 0.5 with 1 and 1 with 5 min application. However the effect was
      relatively small within the range of usual application times (1 to 5 min), and
      64% of the MMC was delivered to the sclera within the first min.

PMID- 11324978
TI  - Ocular complications of latanoprost in uveitic glaucoma: three case reports.
AB  - The purpose of this study was to report paradoxical reaction on the intraocular
      pressure after treatment with latanoprost in 3 cases of uveitic glaucoma. Serial
      clinical examinations of intraocular pressure by means of daily tonometric curves
      were performed in three patients with uveitic glaucoma before and after the
      beginning of latanoprost therapy. All measurements were performed by two doctors,
      but every patient's IOP was always measured by the same doctor. Adverse
      reactions, such as increased intraocular pressure and recurrence of inflammation,
      were noted to occur 7 to 16 days after rechallenging with topical latanoprost
      therapy for glaucoma in patients with history of uveitic glaucoma. The conclusion
      indicates that clinicians should be alerted to these possible complications of
      topical latanoprost therapy in uveitic glaucoma.

PMID- 11324979
TI  - Liposomal prostaglandin E1 enhances optic nerve head blood flow in cats.
AB  - We investigated the effects of intravenous administration of prostaglandin E1
      (PGE1) and lipo-prostaglandin E1 (lipo-PGE1), on optic nerve head blood flow
      (ONHBF) using ten anesthetized cats. Changes in relative ONHBF were noninvasively
      and continuously measured with fundus camera-based laser Doppler flowmetry. The
      blood pressure (BP) decreased significantly by 6 +/- 5 (mean +/- SD)% and 8 +/-
      4%, respectively, after PGE1 (30, 100 ng/kg/min) administration, but at either of
      these concentrations there were no significant changes in ONHBF. On the other
      hand, with lipo-PGE1 (10 ng/kg/min), the BP remained unchanged, but ONHBF
      increased significantly by 61 +/- 49%. A larger dose of lipo-PGE1 (30 ng/kg/min)
      had opposite effects because the BP decreased significantly by 14 +/- 4% after
      administration, and the ONHBF remained unchanged (i.e., 67 +/- 102%). In all
      cases, there were no changes in IOP. With 10 ng lipo-PGE1, the large increase in
      ONHBF can be accounted for by vasodilation since perfusion pressure was
      unchanged. The inability of 30 ng lipo-PGE1 to affect ONHBF could be ascribed to
      the decrease in BP resulting in decreased ocular circulation. These results
      suggest that, in humans, lipo-PGE1 may also increase ONHBF provided that it is
      used at doses that do not produce large decreases in BP.

PMID- 11324980
TI  - Tetrahydrobiopterin reverses the impairment of acetylcholine-induced
      vasodilatation in diabetic ocular microvasculature.
AB  - The purpose of this study is to test whether tetrahydrobiopterin, an essential
      cofactor in nitric oxide synthesis, can reverse endothelium dysfunction in
      diabetic ocular circulation. Using the streptozotocin-induced diabetic rat model
      and the isolated perfusion eye technique, the response to the acetylcholine (an
      endothelium-dependent vasodilator mediated by stimulated nitric oxide release)
      induced vasodilatation of the diabetic ocular vasculature before and after
      tetrahydrobiopterin administration was compared. Age matched normal rats were
      used for reference response. Six streptozotocin-induced diabetic rats and eleven
      control rats at 21.5 +/- 0.2 weeks and 21.2 +/- 2.1 weeks postinduction,
      respectively, were used. The dose response curve from the diabetic eyes was found
      to be significantly different from that of the control eyes (p < 0.001) with
      significantly reduced responses to 10(-4)M acetylcholine. After 30 min of
      administration of tetrahydrobiopterin to the diabetic eyes, however, the
      acetylcholine-induced vasodilatation response was significantly (p < 0.001)
      increased compared with the response prior to tetrahydrobiopterin administration.
      The vasodilatory response in the diabetic eyes after tetrahydrobiopterin
      administration was at a level that was comparable with the control response (p =
      0.742). We have shown that acute administration of tetrahydrobiopterin is
      effective in reversing to control level the impaired acetylcholine-induced
      vasodilatory response at 21.5 +/- 0.2 weeks postinduction. Our result suggests
      that a decreased level of tetrahydrobiopterin in the eyes of the streptozotocin
      induced diabetic rats may be responsible for the ocular vascular endothelium
      dysfunction.

PMID- 11324981
TI  - Effects of lomerizine, a novel Ca2+ channel blocker, on the normal and endothelin
      1-disturbed circulation in the optic nerve head of rabbits.
AB  - We examined the effects of lomerizine, a new diphenylmethylpiperazine Ca2+
      channel blocker, on the normal circulation in the optic nerve head and long
      posterior ciliary artery, and on endothelin-1-induced hypoperfusion in the optic
      nerve head in anesthetized rabbits using a hydrogen gas clearance method and
      laser Doppler flowmetry. These effects were compared with those of nilvadipine
      and pranidipine. Lomerizine (0.1 and 0.3 mg/kg, i.v.) significantly increased
      tissue blood flow in the optic nerve head and the putative blood flow in the long
      posterior ciliary artery with smaller reduction of blood pressure (0.3 mg/kg,
      i.v.) and without change in heart rate. On the other hand, nilvadipine (0.003 and
      0.01 mg/kg, i.v.) and pranidipine (0.003 and 0.01 mg/kg, iv.) each significantly
      increased blood flow and lowered blood pressure. Moreover, lomerizine (0.1 and
      0.3 mg/kg, i.v.) and nilvadipine (0.01 mg/kg, i.v.), when administered 5 min
      before an endothelin-1 injection (10(-6) M, 100 microl), inhibited the
      hypoperfusion in the optic nerve head. These results suggest that lomerizine
      improves the ocular circulation with minimal cardiovascular side effects.
      Therefore, lomerizine may have clinical potential for the treatment of eye
      diseases associated with local circulatory disturbances, such as normal-tension
      glaucoma.

PMID- 11324982
TI  - Effects of protein tyrosine kinase inhibitor genistein on retinal function in
      superfused vertebrate retina.
AB  - The aim of this study was to evaluate safe concentrations of genistein for a
      potential intraocular application using the isolated retina technique on bovine
      retina preparations. Bovine retinas were isolated and perfused with an oxygen pre
      equilibrated standard solution. The electroretinogram (ERG) was recorded as a
      transretinal potential using silver/silver-chloride electrodes. After recording
      of stable ERG amplitudes, genistein was added to the solution in different
      concentrations. The percentage of b-wave reduction under the drug was calculated.
      We also studied the influence of genistein on the a-wave amplitude. After the
      addition of aspartate, the b-wave amplitude was reduced continuously until
      unmasked a-wave amplitudes were reached. Genistein was then added to the
      aspartate containing perfusate. The percentage of a-wave amplitude reduction
      under the drug was calculated. Concentrations of 3.3 microMol/l and higher were
      found to reduce the b-wave amplitude. The a-wave amplitude was not changed by the
      applied concentrations. The ERG only showed toxic effects from genistein beyond
      concentrations that were found to inhibit endothelial cell growth in vitro. In
      previous studies, beneficial effects on trabecular meshwork cells were present
      for genistein concentrations which are distinctly higher than the maximum
      nontoxic concentration reported here. It was shown that the photoreceptor layer
      is not affected at the examined concentration range. Therefore, we attribute the
      toxic effects to postsynaptic interaction of genistein. Intraocular application
      of genistein in a sufficient concentration seems possible.

PMID- 11324983
TI  - In vitro corneal permeation of unoprostone isopropyl (UI) and its metabolism in
      the isolated pig eye.
AB  - The corneal permeability, hydrolysis, and metabolism of unoprostone isopropyl
      (UI), a docosanoid, were examined in isolated porcine ocular tissues. The
      apparent permeability coefficient (Papp) of the esterified prodrug and of the
      acid metabolite were determined in a modified Valia-Chien permeation chamber and
      quantified by high performance liquid chromatography. Enzymatic hydrolysis and
      subsequent metabolism were examined in isolated tissue homogenates. The prodrug
      (ester form) was found to permeate the isolated intact porcine cornea with a Papp
      of 9.47 x 10(-7) cm/sec. Only the acid metabolite could be detected in the
      receiver chamber, indicating the requirement of hydrolysis for permeation. The
      acid metabolite could not permeate the intact cornea but was able to cross an
      epithelium-denuded cornea with a Papp of 1.22 x 10(-6) cm/sec. Enzymatic
      hydrolysis of UI was confined to the isolated intact cornea and epithelium,
      indicating that the esterase activity was localized in the corneal epithelium.
      Incubations with different porcine ocular tissues, conjunctiva, iris-ciliary
      body, trabeculum, as well as aqueous humor, did not reveal other metabolites.
      These findings demonstrate that the ocular penetration of UI is dependent on its
      uptake into the epithelium and subsequent hydrolysis prior to its penetration
      into the anterior chamber, a very common pathway for ophthalmic drugs. In the pig
      eye, unoprostone does not appear to be further metabolized.

PMID- 11324984
TI  - Ocular safety of INS365 ophthalmic solution: a P2Y(2) agonist in healthy
      subjects.
AB  - The purpose of this study was to evaluate the ocular safety and tolerability of
      the P2Y(2) receptor agonist, INS365, when applied as eye drops in normal human
      subjects. This study was a double-masked, placebo-controlled, randomized, within
      subject paired-comparison, dose-escalation study in five cohorts of ten healthy
      subjects. The concentrations of INS365 ophthalmic solution were 0.5, 1.0, 2.0,
      and 5.0% given three times over six hours. Safety was assessed by general and
      ophthalmic examination and symptomatology. Unanesthetized Schirmer tests were
      performed in the last cohort of 10 subjects to evaluate the acute effects of
      INS365 on tear secretion. There were no significant differences in the number of
      subjects with ocular events reported in placebo-treated eyes compared to INS365
      treated eyes. Two adverse events were possibly related to INS365: painless
      blepharospasm and an increase in lacrimation after 5.0% INS365 instillation.
      Unanesthetized Schirmer testing showed no acute effects of INS365 on tear
      secretion, compared to its vehicle, in healthy subjects, in which reflex tearing
      often produced maximal Schirmer values. INS365 ophthalmic solution was well
      tolerated when administered by ocular instillation. Stimulation of ocular surface
      P2Y(2) receptors was not associated with ocular tolerability issues in healthy
      subjects.

PMID- 11324985
TI  - Review: uveitis and immunosuppressive drugs.
AB  - Uveitis, inflammation of the eye, is a common occurring disease resulting from a
      wide variety of traumatic and immunogenic insults and, in most cases, can be
      treated successfully by corticosteroids. However, corticosteroids have severe
      side effects. Alternative therapy is using nonsteroidal anti-inflammatory agents
      like indomethecin, diclofenac and flurbiprofen. The uveitic cases are prominent
      in the third world countries, and many of the patients are not responsive or
      become refractory to steroidal or nonsteroidal therapy. Therefore, there is
      another class of compounds "immunosuppressive drugs" found to be successful in
      treating uveitis. These include cyclosporin A, tacrolimus, and sirolimus.
      However, being immunosuppressive they also have side effects. Therefore, the
      effective therapy with lower side effects is the treatment with combination of
      these drugs in lower dosages. Cyclosporin A plus sirolimus or tacrolimus in
      threshold doses alleviate signs of uveitis with lower incidence of side effects.

PMID- 11324986
TI  - Review: effects of nitric oxide on eye diseases and their treatment.
AB  - Both underproduction and overproduction of nitric oxide (NO) could lead to
      various eye diseases. It is known that endothelial NO synthase (eNOS) and
      neuronal NOS (nNOS) are activated in normal tissues to produce NO for
      physiological functions. Thus, underproduction of NO results in various eye
      diseases which could be corrected by providing NOS substrates or NO donors to
      lower the intraocular pressure, increase ocular blood flow, relax ciliary muscle,
      etc. On the other hand, immunological NOS (iNOS) is inducible only in
      pathological conditions by endotoxins, inflammation, and certain cytokines, such
      as interleukin-1 (IL-1), IL-6, TNF (tumor necrosis factor) and the like. Once
      induced, iNOS will produce large amounts of NO for long periods of time, so that
      NO is converted into NO2, nitrite, peroxynitrite and free radicals to induce
      pathophysiological actions, such as optic nerve degeneration and posterior
      retinal degeneration lesion, which lead to glaucoma, retinopathy, age-related
      macular degeneration (AMD), myopia, cataracts and uveitis. To treat/prevent these
      eye diseases, inhibitors of iNOS activity and/or iNOS induction could be tried.

PMID- 11324987
TI  - Heart rate and orthostatic stress.

PMID- 11324988
TI  - Effects of cholinergic and beta-adrenergic blockade on orthostatic tolerance in
      healthy subjects.
AB  - Cardiovascular responses during a graded lower body negative pressure (LBNP)
      protocol were compared before and after atropine and propranolol administration
      to test the hypothesis that both sympathetic and parasympathetic control of
      cardio-acceleration are associated with syncopal predisposition to orthostatic
      stress in healthy subjects. Eleven men were categorized into two groups having
      high (HT, N = 6) or low (LT, N = 5) tolerance based on their total time before
      the onset of presyncopal symptoms. HT and LT groups were similar in physical
      characteristics, fitness, and baseline cardiovascular measurements. Atropine
      treatment had no effect on LBNP tolerance or mean arterial pressure at
      presyncope, despite an atropine-induced increase in heart rate. Propranolol
      treatment reduced (p<0.05) LBNP tolerance in both groups. Diminished LBNP
      tolerance after propranolol administration was associated with reductions in
      cardiac output, whereas increase in systemic peripheral resistance from baseline
      to presyncope was unaffected by propranolol. Reduction in cardiac output and LBNP
      tolerance after beta blockade reflected a chronotropic effect because lower LBNP
      tolerance for the HT (-50%) and LT (-39%) groups was associated with dramatic
      reductions (p <0.05) in the magnitude of LBNP-induced tachycardia without
      significant effects on stroke volume at presyncope. Absence of an atropine
      induced difference in cardiac output and systemic peripheral resistance between
      HT and LT groups failed to support the notion that cardiac vagal withdrawal
      represents a predominant mechanism that could account for differences in
      orthostatic tolerance. Because a reduction in LBNP tolerance in both HT and LT
      groups after propranolol treatment was most closely associated with reduced
      tachycardia, the data suggest that a primary autonomically mediated mechanism for
      maintenance of mean arterial pressure and orthostatic tolerance in healthy
      subjects is beta adrenergic-induced tachycardia.

PMID- 11324990
TI  - Valsalva-induced syncope during apnea diving.
AB  - A young man had two dangerous episodes of transient loss of consciousness during
      apnea diving in a swimming pool. Medical and neurologic examination results were
      normal. Standard autonomic test results (including heart rate variability,
      baroreflex sensitivity, tilt-table test, and Valsalva ratio) were unremarkable,
      with the exception of an increased blood pressure decrease during early phase II
      of the Valsalva maneuver. Syncope with arrhythmic myoclonic jerks could be evoked
      by a strong straining maneuver. Simultaneous physiologic recordings showed
      extreme blood pressure and cerebral blood flow velocity decreases and
      electroencephalographic slowing during syncope. The electrocardiogram showed a
      continuous sinus rhythm with a progressive tachycardia. The authors' findings
      were not compatible with baroreflex failure or vasovagal mechanisms (Bezold
      Jarisch reflex activation) as the underlying causes. The authors concluded that
      mechanical factors (strong reduction of blood reflux to the heart) in combination
      with a reduced threshold of the brain for developing ischemia-related arrhythmic
      myoclonic jerks were responsible for Valsalva-induced syncope in the patient.

PMID- 11324991
TI  - Treatment of vasovagal syncope: pacemaker or crossing legs?
AB  - A 50-year-old male patient continued to experience syncope after implantation of
      a pacemaker. During cardiovascular examination, the patient showed a typical
      vasovagal response, with normal pacemaker function. Leg crossing, which prohibits
      the pooling of blood in the legs and abdomen, at the onset of symptoms helped to
      prevent this response. The authors recommend a course of leg crossing as a
      measure to treat vasovagal syncope.

PMID- 11324989
TI  - Suppressed sympathetic skin response in Parkinson disease.
AB  - The sympathetic skin response (SSR) was used to evaluate sympathetic sudomotor
      activity in Parkinson disease (PD) and the effects of antiparkinsonian medication
      on the disease. We recorded SSRs to electric and auditory stimulation in 58
      untreated patients with PD and in 20 healthy controls. In addition to amplitude
      and latency measurements, we examined the number of SSRs evoked by a single
      stimulus and the response adaptation after repetitive stimuli. The patients with
      PD subsequently were randomized for administration of levodopa/ carbidopa (n =
      19), bromocriptine (n = 20), or selegiline (n = 19) as their initial treatment.
      The measurements were repeated after 6 months of medication and after a washout
      period. SSR amplitudes were significantly lower in patients with PD than in the
      control subjects at baseline. The amplitude reduction was more pronounced in
      patients with high Unified Parkinson's Disease Rating Scale scores, in those with
      high tremor scores, and in those with PD symptoms that had lasted more than 1
      year. The levodopa/carbidopa and bromocriptine treatments did not influence SSRs,
      although selegiline slightly decreased the amplitude. The synchronous responses
      after a single stimulus were more often repetitive in the patients with PD than
      in the controls, although the response adaptation tendencies were similar. In
      conclusion, the degenerative process in PD involves the sudomotor system as
      reflected by the progressive suppression of SSR amplitudes with a correlation to
      PD symptom duration and clinical disability, whereas PD medications seems to have
      only minor effects. The changes in amplitude and the repetitiveness of SSRs with
      normal adaptation may be caused by deficits at several levels of the SSR reflex
      arch.

PMID- 11324992
TI  - The benefit of pulmonary metastectomy for bone and soft tissue sarcomas.
AB  - The outcome of patients having metastectomy for pulmonary metastases from locally
      controlled primary malignancy of bone and soft tissue of the limbs is compared to
      a similar group deprived of such therapy. Forty patients receiving pulmonary
      metastectomy and 18 patients who were candidates for, but did not receive,
      metastectomy were compared by age, sex, histology, number of metastases,
      synchronous and metachronous presentation of metastases and the use of
      chemotherapy. The only variable correlated with survival was metastectomy.
      Surgical mortality was 0%, complications occurred following 11.7% of the
      procedures. Survival of the 40 metastectomised patients (median 60 months) was
      better than that of the 18 patients not operated upon (median 28 months; P =
      0.02). For osteosarcoma, median survival was 51 months versus 30 months,
      respectively (P = 0.004). Median survival for patients undergoing pulmonary
      metastectomy was twice that of those not receiving metastectomy. The number and
      time of appearance of metastases does not appear to be a deterrent.

PMID- 11324993
TI  - Surgical treatment of multinodular goiter: incidence of lesions of the recurrent
      nerves after total thyroidectomy.
AB  - The problems concerning surgical goiter treatment are discussed, particularly the
      morbidity of total thyroidectomy and possible injury to recurrent nerves in
      comparison to the partial resection of the gland. We discuss our case material
      and review the literature. We conclude that total thyroidectomy seems to be the
      most effective surgical procedure with lower morbidity than subtotal
      thyroidectomy.

PMID- 11324994
TI  - Surgical treatment of substernal goiter.
AB  - BACKGROUND: Substernal goiter differs from its cervical counterpart in regard to
      its clinical presentation, surgical management, pathological analysis and
      postoperative complication. METHODS: Retrospective analysis of 1320
      thyroidectomies performed at the Hacettepe University Hospital between 1990 and
      1997. RESULTS: 30 (2.3%) of 1320 thyroidectomies underwent operation for removal
      of substernal goiters in an 8-year period. The most common symptom was cervical
      mass (67%) and 33% of the patients were asymptomatic. Computerised tomography was
      the most accurate pre-operative test for detecting substernal extension.
      Substernal goiters were removed by collar incisions in 93% of the cases. The
      pathology was generally found to be benign (94%), but follicular carcinoma was
      present in two (6%) patients. There was no mortality and no complications were
      observed in 73% of the patients. CONCLUSIONS: The presence of substernal goiter
      is an indication for removal given the lack of any effective medical therapy, low
      surgical morbidity, risk of malignancy and acute obstructing symptoms.

PMID- 11324995
TI  - Papillary thyroid carcinoma in thyroglossal duct cyst.
AB  - Thyroglossal duct remnants are the most common midline neck swellings, but
      carcinoma is found in approximately 1% of these lesions. The cysts are usually
      asymptomatic and the presentation of the patient with carcinoma is
      indistinguishable from the common cyst. Papillary adenocarcinoma comprises 75-85%
      of the tumors reported. A 36-year-old woman underwent Sistrunk procedure for
      excision of a thyroglossal cyst. No thyroid abnormality was noted pre-operatively
      nor during the surgical examination. The histopathological examination revealed
      papillary carcinoma. She has been maintained on thyroxine suppression and was
      doing well at 14 months' follow-up. Carcinoma of the thyroglossal duct cyst is
      rare. The ultrasonographic examination should be performed pre-operatively for
      thyroid gland study. The main question is what to do with the thyroid gland.
      There still is controversy about thyroid removal for a papillary carcinoma, but
      all the patients should receive suppressive doses of thyroid hormone. As the cure
      rate is 95% for the patients whose thyroid is preserved and further postoperative
      complications are avoided, we can consider that the optimal surgical procedure
      for thyroglossal duct carcinoma is the same as that for the benign cyst.

PMID- 11324997
TI  - Extended (D2) lymphadenectomy in gastric cancer: a five year experience.
AB  - The extent of lymph node dissection in stomach adenocarcinoma is currently under
      debate. Japanese data strongly support the therapeutic value of extended
      lymphadenectomy (D2 node dissection), whereas in Western countries several
      prospective trials have recently been completed with contrasting results. During
      the period May 1993 to May 1998, 164 patients with gastric cancer were observed:
      136 patients, treated with a radical surgical procedure including lymph node
      dissection according to the guidelines of the Japanese Research Society for
      Gastric Cancer, were eligible for our analysis. Clinical, histopathological, and
      surgical factors were examined for their influence on long-term survival. Our
      results on morbidity and mortality rates are similar to Japanese series: we
      suggest that the experience and training of the surgeon and his personal attitude
      towards extensive lymph node dissection may, therefore, be a major factor
      influencing the morbidity associated with the procedure. The relatively high
      estimated 3-year survival rate (52%) suggests support for extended
      lymphadenectomy (D2 dissection) in gastric cancer as standard treatment.

PMID- 11324996
TI  - Prospectively performed modified D1 lymphadenectomy for clinically diagnosed
      mucosal, node negative gastric cancer: findings over the past decade.
AB  - Based on retrospective analyses demonstrating the low probabilities of both lymph
      node metastasis and recurrence of curatively resected mucosal gastric cancer, we
      have established criteria for modified D1 lymphadenectomy (lymphadenectomy in the
      perigastric region as well as along the left gastric artery) and performed this
      in a prospective manner. In this study, we evaluate our treatment strategy by
      reviewing the patients prospectively undergoing modified D1 lymphadenectomy. The
      clinicopathological characteristics and survival data of 138 patients who
      underwent modified D1 lymphadenectomy between 1987--when we first introduced
      endoscopic ultrasonography--and 1996 were analyzed. The criteria for modified D1
      lymphadenectomy were mucosal, node negative gastric cancer by pre-operative and
      intra-operative examinations. Depth of invasion was correctly diagnosed in 80% of
      the patients. Among the resultant submucosal gastric cancer patients, the
      incidence of slight submucosal invasion was increased in the second half-period
      (78%) as compared with that in the first half-period (44%). Nodal involvement was
      observed in 4 patients (2.9%); all of them exhibited the depressed type with
      ulceration and a histologically high grade of gastric cancer. Because their
      metastasized lymph nodes were all confined to the perigastric region, surgical
      treatment resulted in no residual cancer macroscopically. No patients succumbed
      to gastric cancer within the median and mean follow-up periods of over 6 years.
      These results suggest that our modified D1 lymphadenectomy is an effective option
      for the pre-operatively and intra-operatively diagnosed mucosal, node negative
      gastric cancer which meets our criteria.

PMID- 11324998
TI  - Vascular invasion of early gastric cancer at resection line.
AB  - Vascular invasion is observed in early gastric cancers (EGCs) as well as advanced
      gastric cancers. However, there have been no studies assessing adequate surgical
      margins for EGCs with reference to vascular invasion. A total of 452 EGCs were
      retrospectively evaluated. Vascular invasion, via lymphatics and/or venous
      vessels, was examined histologically. The distance from the tumor edge to
      infiltration was measured when cancer cells extended beyond the tumor through
      vessels. Vascular invasion was histologically confirmed in 41 EGCs (9.1%).
      Invasion was in one-fourth (40/166, 24.1%) of submucosal cancers, but in only one
      (1/286, 0.3%) mucosal cancer. Five EGCs (1.1%) showed infiltration beyond the
      tumor through the vessels and the maximum distance from the tumor edge to the
      most distal site of infiltration was 4 mm. In conclusion, a 2 cm surgical margin,
      as recommended in Japanese surgical textbooks, is adequate for EGCs with
      reference to vascular invasion.

PMID- 11324999
TI  - The role of surgery in the treatment of primary gastric lymphoma.
AB  - The present retrospective study of 23 patients with primary gastric lymphoma had
      the objective of determining the role of surgical treatment on survival. All
      patients were submitted to gastric resection with regional lymph node removal.
      Nine patients (39.1%) received supplementary treatment (chemotherapy and/or
      radiotherapy). According to the Kiel classification, the most frequent
      histological type was the centroblastic (29.1%), and most patients (60.9%) had a
      low-grade lymphoma. According to the Ann Arbor classification, modified by
      Musshoff and Schmidt-Vollmer, stages were IE in 52.1%, II1E in 8.7%, II2E in
      13.1%, and IV in 26.1% of the cases. Mean survival was 29.3 months. The variables
      that influenced survival rates were age, advanced stage tumor, and receiving
      postoperative adjuvant therapy. Analysis of our cases suggests that complete
      lesion resection along with adjacent lymph nodes, and supplementary postoperative
      treatment is the best approach for a resectable primary gastric lymphoma.

PMID- 11325000
TI  - Primary intestinal obstruction complicated by persistent descending mesocolon.
AB  - Persistent descending mesocolon is an uncommon developmental anomaly which
      results from failure of fusion of the descending mesocolon with the posterior
      parietal peritoneum. It is asymptomatic in most cases and rarely causes
      intestinal obstruction. We report here a case of primary intestinal obstruction
      complicated by a persistent descending mesocolon. A 66-year-old man without prior
      laparotomy was admitted with a diagnosis of small bowel obstruction. Pre
      operative investigation demonstrated a segmental jejunal stenosis and a
      persistent descending mesocolon as possible causes of the obstruction. Laparotomy
      showed that the cause of the obstruction was the jejunal stenosis, not the
      persistent descending mesocolon. The stenosis was resected, but correction of the
      anomaly was not performed. The patient made an uneventful recovery after the
      operation. From our limited experience, persistent descending mesocolon need not
      be surgically corrected when it is not considered to be the cause of obstruction
      and another definite cause co-exists.

PMID- 11325001
TI  - Biliary-colonic fistula through a cystic duct stump.
AB  - BACKGROUND AND METHODS: Biliary-colonic fistulas are a known, but unusual,
      complication of gallstone disease. Fistulas occurring after cholecystectomy
      between cystic duct stump (CDS) and the colon are extremely rare; only two cases
      have been previously reported in the literature. We report a third case, and
      discuss the diagnostic work-up and management of this entity. RESULTS: Biliary
      colonic fistulas usually present with biliary and septic complications. ERCP and
      barium enema play an important diagnostic role. Treatment is mainly surgical,
      with division of the fistula and excision of the CDS. CONCLUSIONS: CDS-colonic
      fistulas should be in the differential diagnosis of any patient presenting with
      sepsis after cholecystectomy. The fistula usually necessitates surgical division.
      Long CDS seen with laparoscopic cholecystectomy may lead to increase in the
      incidence of this entity.

PMID- 11325002
TI  - Intracystic pressure and viability in hydatid disease of the liver.
AB  - BACKGROUND: Knowledge on the viability of hydatid cysts of the liver during
      operation is important to the surgeon may dictate the peri-operative therapeutic
      manoeuvre undertaken. PATIENTS AND METHODS: A prospective study was performed on
      23 patients with 28 hydatid cysts of the liver to assess whether intracystic
      pressure (ICP) could predict viability of protoscoleces. All patients received
      albendazole (10 mg/kg body weight/day) for 5 days pre-operatively. The ICP was
      measured from the apex of the cyst, after laparotomy, using a 16-G needle
      connected to a water manometer. After manometry, the cyst contents were aspirated
      and the viability of protoscoleces assessed by their flame cell activity,
      motility and ability to exclude 5% aqueous eosin. RESULTS: The median ICP was 54
      +/- 21 cmH2O for 17 viable cysts and zero for 8 non-viable cysts, while 1
      additional non-viable cyst and 2 sterilized cysts had high ICP (sensitivity,
      100%; specificity, 72%; accuracy, 89%). The median diameter of the viable cysts
      was 9.3 +/- 3.5 cm and the non-viable cysts 10.7 +/- 2.6 cm. In the right lobe
      were located 12 viable and 8 non-viable cysts and in the left lobe, 5 viable and
      3 non-viable cysts. No significant difference in diameter or ICP were noted
      between the hepatic lobes. CONCLUSIONS: These findings suggest that the
      measurement of ICP is a simple, cheap and reliable method for assessment of the
      viability of hydatid cysts of the liver.

PMID- 11325003
TI  - Surgical treatment of hepatic caudate lobe metastases originating from colorectal
      primaries.
AB  - Malignant tumor resection of the hepatic caudate lobe has recently received
      attention. However, there are few reports about metastatic liver tumor in the
      caudate lobe from colorectal carcinoma, and its clinical features still remain
      unknown. In this paper, three patients operated on in our institute and 15
      reported cases from the published literature were analyzed in order to reveal
      clinical features of this disease. Many cases had advanced liver tumors, such as
      invasion in to major vessels at the time of operation. Isolated complete caudate
      lobectomy was performed in 8 patients and major hepatectomy was carried out in 6
      instances. Seven cases also underwent partial resection of the inferior vena
      cava. Recurrence of disease was observed in 11 patients: seven cases had relapse
      only in the residual liver, five of whom underwent another hepatectomy. The
      median survival time of those patients who died was 25 months, and that of seven
      cases with IVC resection, 18 months. Two patients out of five who received a
      second hepatectomy survived for longer than 90 months. It is suggested that
      aggressive surgical treatment including repeated hepatectomy results in the
      prolongation of survival. Earlier diagnosis and surgical treatment at a more
      appropriate stage of the disease may further improve the survival rate.

PMID- 11325004
TI  - Haemodynamic and metabolic changes during major liver resection with use of
      hepatic total vascular exclusion.
AB  - We evaluated haemodynamic changes during major liver resection that involved
      total hepatic vascular exclusion (HVE) carried out through clamping hepatic
      pedicle and inferior caval vein upper and above the liver. Fourteen patients,
      undergoing different procedures of major liver resection, were enrolled in this
      study which used complete cardiovascular monitoring. Haemodynamic parameters were
      measured and calculated at five different times during the operation. Changes
      such as reduction in cardiac output and increase in systemic vascular resistance,
      though significant, were well tolerated in all patients, allowing the execution
      of major liver surgery. HVE offers a significant reduction in haemorrhagic and
      air embolus risk, but it requires the use of complete haemodynamic monitoring to
      evaluate tolerance to clamping and correction of unavoidable cardiovascular
      changes.

PMID- 11325005
TI  - Primary splenic lymphoma in patient with hepatitis C virus infection: case report
      and review of the literature.
AB  - Primary splenic lymphoma is uncommon, constituting only 1-2% of all patients with
      malignant lymphoma. Despite the rarity of this malignancy, the number of primary
      splenic lymphoma being reported has increased due to its ambiguous definition
      used in the literature. We describe a case of a 41-year-old man with chronic
      hepatitis C virus infection presenting abdominal discomfort in the upper left
      quadrant, weakness, nausea and vomiting. Abdominal computed tomography revealed
      nodules in the congested splenic parenchyma. Splenectomy was performed and an
      analysis of the spleen diagnosed B-cell non-Hodgkin's lymphoma. Biopsy of the
      liver showed evidence of hepatitis C virus. Bone marrow biopsy revealed no tumor
      infiltration. The patient has been followed to date, has progressed quite well
      and remains essentially asymptomatic. Recently, an etiologically important role
      has been suggested for hepatitis C virus infection in the development of B-cell
      non Hodgkin's lymphoma. Lymphotropism of hepatitis C virus may play a
      pathological role in the development of non Hodgkin's lymphoma. It is important
      to add lymphoma to the list of differential diagnosis of extrahepatic disorders
      in patients with chronic hepatitis C virus infection.

PMID- 11325006
TI  - Predictive factors of response to splenectomy in adult chronic idiopathic
      thrombocytopenic purpura.
AB  - A total of 26 surgical patients with chronic idiopathic thrombocytopenic purpura
      (ITP) were reviewed and results of splenectomy were statistically related to age
      and sex, length of and response to pre-operative corticosteroid therapy, pre
      operative platelet count and time interval between diagnosis and surgery. Median
      age was 37 years (range, 17-81 years) and the male:female ratio was 1.16. Pre
      operative platelet count ranged from 2-70 x 10(9)/l. The length of pre-surgical
      corticosteroid therapy (prednisone 1-2 mg/kg/day) varied from 2 weeks to 3 years.
      Steroid therapy was unsuccessful in 15 patients and only achieved temporary
      remission in the remaining 11 cases. The time interval between diagnosis and
      splenectomy ranged from 4-60 months. There were 21 responders (80.4%) and 5 non
      responders (19.6%) to splenectomy. Using the chi-square test, differences in age,
      length and response to pre-operative steroid therapy and diagnosis-to-splenectomy
      interval did not achieve statistical significance when responder and non
      responder groups to splenectomy were compared. Conversely, a significant
      difference was found comparing male to female groups, since 92.9% of males and
      only 66.7% of females were successfully treated by surgery (P approximately
      0.01). In addition, patients with a pre-operative platelet count less than 30 x
      10(9)/l responded at an higher rate (100% versus 70.6%; P approximately 0.05) to
      splenectomy.

PMID- 11325007
TI  - Advances in general and vascular surgical care of Jehovah's Witnesses.
AB  - BACKGROUND: Jehovah's Witnesses are an enlarging religious community in the US
      and throughout the world. Members of this faith refuse administration of blood
      during medical or surgical therapy even if death may occur as a consequence. The
      surgeon is consequently faced with difficulties and moral dilemmas of caring for
      these patients. PATIENTS AND METHODS: From July 1, 1975 to March 1, 1999, the
      author performed 132 general and vascular surgical procedures on pediatric and
      adult patients who were Jehovah's Witnesses. RESULTS: A surgical series of 132
      patients who are Jehovah's Witnesses is reported. The series includes general
      surgical procedures in children and adults. Also, vascular surgical procedures in
      adults are reported. Thirty-one procedures were of significant magnitude to
      possibly require a blood transfusion. No patient in this series received a blood
      transfusion. No patient was refused an indicated surgical procedure. Fourteen
      complications incurred in this series which included one death. The age range of
      patients in this surgical series was 9 months to 91 years. There was no
      difference in the male to female ratio. The spectrum of cases reported represents
      the entire range of procedures seen in general and vascular surgical practices.
      CONCLUSIONS: The surgical care of Jehovah's Witnesses has become less of an
      operative risk over the last decade. There are now significant alternatives to
      the transfusion of blood, such as erythropoietin, iron dextran, aprotinin and
      Fluosol-DA 20%. Technological surgical developments and advances, such as the
      cell saver, argon beam coagulator, acute limited normovolemic hemodilution,
      autologous whole plasma fibrin gel, and controlled hypotensive anesthesia during
      anesthesia have contributed substantially to a reduction in the operative loss of
      blood. The time honored rule of hemoglobin of 10 g/dl and a hematocrit of 30%
      should not require strict adherence in the postoperative care of most patients.
      The acceptance of a lower transfusion trigger point of hematocrit of 22% and a
      hemoglobin of 7 g/dl can significantly reduce transfusion requirements without an
      increase in morbidity. Ethical considerations are discussed and evaluated when
      treatment restrictions, such as blood transfusion and other life-preserving
      therapies are limited by religious beliefs or living wills.

PMID- 11325008
TI  - Subfascial endoscopic ligation of perforator veins (SEPS) in the treatment of
      venous ulcers.
AB  - BACKGROUND: Subfascial endoscopic ligation of perforator veins (SEPS) is
      presently considered the procedure of choice for the treatment of venous ulcers.
      This study was undertaken in order to determine the efficacy and effectiveness of
      SEPS in the treatment of venous ulcers as reported in the literature. DATA: 428
      active ulcers, treated by SEPS are included in this study. SOURCE: Current world
      literature. CONCLUSIONS: 428 active ulcers were treated by SEPS. 17 patients had
      a history of a healed ulcer. 101 patients had moderately severe to severe
      lipodermatosclerosis. 79% of the active ulcers healed on average in 2.3 months,
      with a range of 21 days to 5.4 months. 2.8% recurrent ulcers were identified.
      6.5% of the active ulcers did not heal. 5 active ulcers apparently got worse
      postoperatively. SEPS is both an efficacious and effective procedure in the
      treatment of venous ulcers.

PMID- 11325009
TI  - Sonographic appearance of oxidised cellulose (Surgicel): pitfall in the diagnosis
      of renal vein thrombosis in a transplant kidney.
AB  - We report the misleading sonographic appearance of Surgicel in the diagnosis of
      renal vein thrombosis in a case of kidney transplant and a review of the
      literature. Removal of the Surgicel before closure is advisable to avoid
      misdiagnosis.

PMID- 11325010
TI  - Transplantation of horseshoe kidney en bloc.
AB  - Horseshoe kidney is probably the most common renal fusion anomaly. With the
      continuous donor shortage, transplant surgeons tend to accept donors previously
      considered unsuitable. We present a successful case of en bloc horseshoe kidney
      transplant in a single recipient. The literature is reviewed. The use of
      horseshoe kidneys in transplantation is recommended in selected cases.

PMID- 11325011
TI  - Delayed haemorrhage after pancreatoduodenectomy.

PMID- 11325012
TI  - (1S,2R)-1-Phenyl-2-[(S)-1-aminopropyl]-N,N-diethylcyclopropanecarboxamide (PPDC),
      a new class of NMDA-receptor antagonist: molecular design by a novel
      conformational restriction strategy.
AB  - We have found that milnacipran, a clinically useful antidepressant due to its
      inhibition of the re-uptake of serotonin (5-HT) and noradrenaline, is also a non
      competitive NMDA-receptor antagonist. Based on the cyclopropane structure of
      milnacipran, conformationally restricted analogs were designed and synthesized.
      Of these analogs, (1S,2R)-1-phenyl-2-[(S)-1-aminopropyl]-N,N
      diethylcyclopropanecarboxamide (PPDC) is 30-fold stronger than milnacipran as an
      NMDA-receptor antagonist with virtually no inhibitory effect on the
      neurotransmitter re-uptake. PPDC was identified as a new class of NMDA-receptor
      antagonist because it has a mode of action different from that of the previous
      antagonists; it selectivly binds the GluRepsilon3/GluRzeta1 and
      GluRepsilon4/GluRzeta1 subtype receptors in an agonist-independent allosteric
      manner. Functional assays of PPDC with the Xenopus oocytes system and cultured
      mouse neurons under voltage-clamp conditions confirmed that it acts as a potent
      NMDA-receptor antagonist. PPDC effectively protected against NMDA-induced
      neurotoxicity in both cultured mouse cerebral cortex and delayed neuronal death
      in a gerbil ischemic model. It was also active in a reserpine-treated mouse
      Parkinsons disease model. Thus, PPDC may be a candidate for a clinically useful
      NMDA-receptor antagonist, since the development of previous NMDA-receptor
      antagonists as drugs has been hindered by various undesirable side effects.

PMID- 11325014
TI  - Protective effect of Ninjin-yoei-to on damage to isolated hepatocytes following
      transient exposure to tert-butyl hydroperoxide.
AB  - To establish a simple screening system for estimating efficacy of an agent for an
      oxidative-related lesion, we investigated the damage in isolated rat hepatocytes
      exposed to 75 microM tert-butyl hydroperoxide (t-BuOOH) and then subsequently
      incubated the cells in fresh medium. By electron spin resonance spectroscopy
      analysis using 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), DMPO adducts of tert
      butoxyl radicals and carbon center radicals were detected during the t-BuOOH
      exposure, and DMPO-OH formation was detected after t-BuOOH removal. In t-BuOOH
      exposed cells, the level of phosphatidylcholine hydroperoxide (PCOOH), a
      peroxidative product of biomembranes in the hepatocytes, and the leakage of
      enzymes into the culture medium were significantly increased. An increase in acid
      phosphatase (AP) activity representing lysosome destabilization preceded the
      aspartate oxoglutarate aminotransferase (AST), alanine oxoglutarate
      aminotransferase (ALT) and lactate dehydrogenase (LDH) leakage. Ninjin-yoei-to
      added to the culture medium following the t-BuOOH exposure significantly
      inhibited the PCOOH formation and the leakage of AP, AST, ALT and LDH,
      concentration-dependently. Ninjin-yoei-to at 1 mg/ml in culture medium completely
      diminished these increases in enzyme activities down to the background levels
      found in control experiments and this reduction was greater than the most
      effective alpha-tocopherol concentration of 20 micromol/ml. Considering all of
      these results, it is likely Ninjin-yoei-to may exert its protective effect by
      antioxidative action and membrane stabilization.

PMID- 11325013
TI  - Molecular mechanisms for alpha2-adrenoceptor-mediated regulation of synoviocyte
      populations.
AB  - The sympathetic nervous system has been indicated to influence the severity of
      inflammatory disease including rheumatoid arthritis. In this study, we elucidated
      the effects of catecholamine on the synovial cell populations. Stimulation with
      epinephrine or norepinephrine for 1-2 weeks dose- and time-dependently increased
      the number of synovial A (macrophage-like) cells but decreased that of B
      (fibroblast-like) cells. These responses in A and B cells were inhibited by the
      alpha2-antagonist yohimbine, the G-protein inactivator pertussis toxin and the
      phospholipase C (PLC) inhibitor U-73122. Furthermore, the protein kinase C (PKC)
      inhibitor calphostin C and mitogen-activated protein (MAP) kinase inhibitors
      PD98059 and wortmannin also abolished the norepinephrine effects on A and B cell
      numbers. In A cells cloned from an A and B cell mixture, norepinephrine also
      increased the cell number. In immunoblotting and immunocytostaining analyses,
      among the PKC isozymes, only PKC betaII immunoreactivity was observed in the
      cytoplasm of unstimulated A and B cells. After alpha2-adrenoceptor stimulation,
      PKC betaII immunoreactivity increased in the plasma membranes of both A and B
      cells with decreases in the cytoplasm. These findings indicated that alpha2
      adrenoceptor stimulation of type A and B synoviocytes produced an increase and a
      decrease in the respective cell number, probably through Gi-coupled PLC
      activation and the resulting stimulation of the PKC betaII/MAP kinase.

PMID- 11325015
TI  - Vasorelaxant effects of pramanicin, an anti-fungal agent: selective action on
      endothelial cells.
AB  - A newly discovered antifungal agent, pramanicin, within the therapeutically
      effective concentration range (4-100 microM), inhibits the tone of phenylephrine
      (PE)-precontracted dog carotid arterial rings in a concentration-dependent manner
      and leads to gradual development of relaxation. However, pramanicin had no effect
      on rings precontracted with 100 mM KCl or on endothelium-denuded rings. Thus,
      inhibition by pramanicin of PE-induced contraction was endothelium-dependent.
      Preincubation of 100 microM pramanicin with carotid arterial rings for 30 min did
      not significantly affect the concentration-contraction response to PE, but almost
      completely inhibited the endothelium-dependent relaxation response to subsequent
      addition of 3 microM carbachol or 100 microM pramanicin. This irreversible
      inhibition of endothelium-dependent relaxation, which is independent of
      extracellular Ca2+, suggests possible endothelial cell damage by pramanicin.
      Pretreatment of the endothelium-intact vascular rings with L-N(G)-nitro-arginine
      (100 microM) inhibited the relaxation of PE-precontracted rings induced by 3
      microM carbachol or 100 microM pramanicin, suggesting that the generation of
      nitric oxide (NO) in endothelial cells mediates the slow vascular relaxation
      induced by pramanicin. We conclude that pramanicin has little direct effect on
      the contractility of smooth muscle cells, but causes an initial slow endothelium
      dependent, NO-mediated vascular relaxation. This is followed by a cytotoxic
      effect on vascular endothelial cells, eventually resulting in the loss of
      vasorelaxant function.

PMID- 11325016
TI  - The influence of phosphodiesterase inhibitor, rolipram, on hemodynamics in
      lipopolysaccharide-treated rats.
AB  - Administration of bacterial endotoxin (lipopolysaccharide, LPS) intravenously has
      been noted to produce a shock state, which is characterized by hypotension and
      multi-organ system failure. The aim of the present investigation was to (a)
      examine the influence of rolipram on hemodynamics, plasma levels of tumor
      necrosis factor-alpha (TNF-alpha) levels, and production of inducible nitric
      oxide synthase (iNOS) in the lungs, ex vivo, in LPS-treated rats, and (b)
      determine the cardiovascular effects of a selective alpha1-adrenoceptor agonist,
      methoxamine, in the absence or presence of rolipram in rats treated with LPS.
      Blood pressure, cardiac index, heart rate and arterial resistance were assessed
      in Long-Evans rats anesthetized with thiobutabarbital. Administration of LPS to
      animals resulted in a significant reduction in cardiac index over time. The
      administration of LPS to rats resulted in a substantial rise in the plasma levels
      of TNF-alpha. Furthermore, the injection of LPS resulted in a significant
      increase in the iNOS activity in the lungs. Pre-treatment with rolipram prevented
      the decline in cardiac index in animals that received LPS. Infusion of
      methoxamine into animals injected with rolipram and pre-treated with LPS did not
      result in significant changes in cardiac index. Pre-treatment with rolipram or
      dexamethasone in animals injected with LPS significantly prevented the rise in
      TNF-alpha when compared to the respective values in vehicle-treated animals. Our
      present observations support the view that the cardiac index can be maintained in
      animals treated with LPS independent of iNOS inhibition.

PMID- 11325017
TI  - Role of mast cells in antigen-induced airway inflammation and bronchial
      hyperresponsiveness in rats.
AB  - The participation of mast cells in the induction of antigen-induced airway
      inflammation and bronchial hyperresponsiveness (BHR) to acetylcholine (ACh) was
      investigated using pharmacological agents and mast cell-deficient rats (Ws/Ws). A
      significant increase in the number of leukocytes in bronchoalveolar lavage fluid
      (BALF) and bronchial responsiveness to ACh were observed 24 h after antigen
      (ovalbumin) challenge in sensitized Brown-Norway (BN) rats. Disodium cromoglycate
      and terfenadine did not inhibit antigen-induced airway inflammation and BHR in
      sensitized BN rats. In contrast, cyclosporin A (CyA), FK-506 and prednisolone
      significantly inhibited antigen-induced airway inflammation and BHR in sensitized
      BN rats. In addition, disodium cromoglycate, terfenadine and prednisolone, but
      not CyA and FK-506, inhibited homologous passive cutaneous anaphylaxis in rats.
      Furthermore, a significant increase in the number of leukocytes in BALF and BHR
      was also observed in Ws/Ws rats 24 h after inhalation of antigen; however, the
      magnitude of BHR in Ws/Ws rats was lower than that in the congenic rats. These
      findings suggest that mast cells play a partial role in the development of
      antigen-induced BHR in rats and that the induction of BHR is barely suppressed by
      mast cell stabilizing agents.

PMID- 11325018
TI  - State-dependent inhibition of L-type Ca2+ channels in A7r5 cells by cilnidipine
      and its derivatives.
AB  - Using a whole-cell patch-clamp technique, state-dependent inhibition of
      dihydropyridines (DHP)s was investigated on L-type channels in A7r5 cells.
      Cilnidipine, its derivatives (D-342 and D-69) and nimodipine inhibited the Ba2+
      current. However, cilnidipine and D-342, but not D-69 or nimodipine, accelerated
      current decay. The apparent rank order for the effects on the DHP-sensitive
      decaying component was different from that obtained for inhibition of the peak
      current. The dissociation constants for cilnidipine in the resting and
      inactivated states were estimated to be 190 and 12 nM, respectively. Cilnidipine,
      but not other DHP derivatives, created a faster and voltage-independent component
      (r= 37 ms). The linear relationship between the tau(-1) of the current decay and
      the cilnidipine concentration provided a value of 471 nM for the dissociation
      constant in the open state, suggesting that the current decay is mediated by one
      to-one lower affinity binding of cilnidipine molecules to their binding site. The
      present study demonstrates that structurally related DHPs act in distinct ways to
      inhibit the L-type channel in the resting, open and inactivated states.
      Cilnidipine and some related DHPs probably exert their blocking action on the
      open channel by binding to a receptor distinct from the known DHP-binding site.

PMID- 11325019
TI  - Na+/H+ exchange inhibitor SM-20220 improves endothelial dysfunction induced by
      ischemia-reperfusion.
AB  - Endothelial cells play an important role in the physiologic homeostasis of the
      cerebral circulation. Previously, we showed that the Na+/H+ exchanger (NHE)
      inhibitor SM-20220 (N-(aminoimino-methyl)-1-methyl-1H-indole-2-carboxamide
      methanesulfonate) improved ischemic brain injury. In this study, we investigated
      the effect of SM-20220 on cerebrovascular dysfunction after ischemia-reperfusion,
      focusing on the kinds of dysfunction that involved endothelial function. In
      cultured bovine brain microvascular endothelial cells (BBMCs), the IC50 value for
      the NHE activity of SM-20220 was 4 x 10(-8) M. SM-20220 also reduced the cell
      injury induced by hypoxia/aglycemia-reoxygenation in BBMCs, with statistical
      significance at 10(-7) M (P<0.05). Next, the effect of SM-20220 on disruption of
      the blood-brain barrier and cerebral blood flow were evaluated using transient
      middle cerebral artery (MCA) occlusion models. Intravenous infusion of SM-20220
      (0.4 mg/kg per hour for 1 h) attenuated the extravasation of Evans blue, a blood
      brain barrier disruption indicator, into cerebral tissue on the day after
      transient ischemia (P<0.05). The occlusion of the MCA decreased the cerebral
      blood flow in the MCA territory by about 20%, and only about 45% of the
      preischemic value was recovered at 1-h reperfusion. A bolus injection of SM-20220
      (1 mg/kg, i.v.) improved the postischemic hypoperfusion by about 75%, without
      causing changes in the systemic blood pressure. These results indicate that the
      protective effect of NHE inhibitor on ischemic brain injury may be at least
      partially mediated by the prevention of endothelial dysfunction.

PMID- 11325020
TI  - Phosphate stimulates differentiation and mineralization of the chondroprogenitor
      clone ATDC5.
AB  - ATDC5 cells were employed to examine how inorganic phosphate (Pi) influences
      chondrocytic bone formation. 1) Pi (3 - 30 mM) plus ascorbic acid (50 microg/ml)
      dose-dependently accelerated proliferative differentiation and mineralization of
      ATDC5. 2) Northern blot analysis revealed that 10 mM Pi suppressed expression of
      type II collagen and PTH (parathyroid hormone) / PTH-related peptide (PTHrP)
      receptor, while it accelerated type X collagen expression. 3) Pi (3 - 30 mM) dose
      dependently increased luciferase activity in the cells transfected with 3000 bp
      type X collagen promoter fused to the luciferase gene. The results suggest a
      regulatory role of Pi in endochondral osteogenesis.

PMID- 11325021
TI  - TRK-820, a selective kappa-opioid agonist, produces potent antinociception in
      cynomolgus monkeys.
AB  - TRK-820 ((-)-17-cyclopropylmethyl-3,14b-dihydroxy-4,5a-epoxy-6b-[N-methyl-trans-3
      (3-furyl)acrylamide]morphinan hydrochloride) has been shown to be a potent opioid
      kappa-receptor agonist with pharmacological properties different from those
      produced by kappa1-opioid receptor agonists in rodents. To ascertain whether or
      not these properties of TRK-820 would be extended to primates, the
      antinociceptive effect of TRK-820 was evaluated in cynomolgus monkeys by the hot
      water tail-withdrawal procedure. TRK-820 given intramuscularly (i.m.) produced a
      potent antinociceptive effect that was 295- and 495-fold more potent than
      morphine with the 50 degrees C and 55 degrees C hot-water tests, respectively,
      and 40-fold more potent than U-50,488H and 1,000-fold more potent than
      pentazocine in the 50 degrees C hot-water test. The duration of antinociceptive
      effects of TRK-820 treatment (0.01 and 0.03 mg/kg, i.m.) lasted more than 6 h,
      which was much longer than those of U-50,488H. The antinociception produced by
      the higher dose (0.03 mg/kg, i.m.) of TRK-820 was not inhibited by nor
      binaltorphimine (3.2 and 10 mg/kg, s.c.) or by naloxone (0.1 mg/kg, s.c.),
      although the antinociception induced by a lower dose of TRK-820 (0.01 mg/kg,
      i.m.) was inhibited by nor-binaltorphimine (10 mg/kg, s.c.). The same doses of
      nor-binaltorphimine and naloxone effectively inhibited the antinociception
      induced by the higher doses of U-50,488H (1.0 mg/kg, i.m.) and morphine (10
      mg/kg, i.m.), respectively. These results indicate that the antinociception
      induced by TRK-820 is less sensitive to nor-binaltorphimine and suggest that it
      is mediated by the stimulation of a subtype of kappa-opioid receptor different
      from the kappa-opioid receptor in cynomolgus monkeys.

PMID- 11325022
TI  - The properties of carbachol-activated nonselective cation channels at the single
      channel level in guinea pig gastric myocytes.
AB  - We investigated the properties of carbachol (CCh)-activated nonselective cation
      channels (NSC(CCh)) at the single channel level in the gastric myocytes of guinea
      pigs using a magnified whole-cell mode or an outside-out mode. The channel
      activity (NPo) recorded in a magnified whole-cell mode increased with
      depolarization (from -120 to -20 mV) and had the half activation potential of -81
      mV under the symmetrical 140 mM Cs+ condition. The single channel conductance
      depended upon the extracellular monovalent cations with the order of Cs+ (35 pS)
      > Na+ (25 pS) > Li+ (21 pS). The channel activities markedly diminished or
      disappeared when external Cs+ was replaced with Na+ or N-methyl-D-glucamate
      (NMDG+). With Cs+ and Na+ as external cations, the channel showed a monotonic
      increase in NPo with the increased mole fraction of Cs+ over Na+, and it had an
      intermediate conductance value in solution containing 67% Cs+ with 33% Na+. These
      data suggested that the extracellular monovalent cations regulate the whole-cell
      current of NSC(CCh) by modulating both the open state probability and the unitary
      conductance, and there is one binding site for the extracellular cations within
      the pore.

PMID- 11325023
TI  - Comparative study on the vasorelaxant effects of three harmala alkaloids in
      vitro.
AB  - Three psychological active principles from the seeds of Peganum harmala L.,
      harmine, harmaline and harmalol, showed vasorelaxant activities in isolated rat
      thoracic aorta preparations precontracted by phenylephrine or KCl with rank order
      of relaxation potency of harmine > harmaline > harmalol. The vasorelaxant effects
      of harmine and harmaline (but not harmalol) were attenuated by endothelium
      removal or pretreatment with a nitric oxide (NO) synthase Nomega-nitro-L-arginine
      methyl ester. In cultured rat aortic endothelial cells, harmine and harmaline
      (but not harmalol) increased NO release, which was dependent on the presence of
      external Ca2+. In endothelium-denuded preparations, pretreatment of harmine,
      harmaline or harmalol (3-30 microM) inhibited phenylephrine-induced contractions
      in a non-competitive manner. Receptor binding assays indicated that all 3
      compounds interacted with cardiac alpha1-adrenoceptors with comparable affinities
      (Ki value around 31 - 36 microM), but only harmine weakly interacted with the
      cardiac 1,4-dihydropyridine binding site of L-type Ca2+ channels (Ki value of 408
      microM). Therefore, the present results suggested that the vasorelaxant effects
      of harmine and harmaline are attributed to their actions on the endothelial cells
      to release NO and on the vascular smooth muscles to inhibit the contractions
      induced by the activation of receptor-linked and voltage-dependent Ca2+ channels.
      The vasorelaxant effect of harmalol was not endothelium-dependent.

PMID- 11325024
TI  - Involvement of tyrosine hydroxylase upregulation in cyclosporine-induced
      hypertension.
AB  - To identify the mechanism of cyclosporine-induced hypertension, we studied the
      effect of cyclosporine on the catecholamine synthetic pathway in rats. We
      administered cyclosporine (10 mg/kg per day, s.c.) for 3 days to 10-week-old male
      Wistar rats. Systolic blood pressure increased significantly in the cyclosporine
      treated group in comparison to that in the control group. Norepinephrine and
      epinephrine levels in the adrenal medulla and plasma of cyclosporine-treated rats
      were also significantly higher than levels in the control rats. Moreover,
      tyrosine hydroxylase (TH) activity and TH mRNA expression in the adrenal medulla
      of cyclosporine-treated rats were significantly elevated. Administration of the
      TH inhibitor alphamethyl-p-tyrosine (200 mg/kg, b.i.d., s.c.) for 3 days
      significantly suppressed cyclosporine-induced increases in systolic blood
      pressure. Phosphorylation of cyclic AMP responsive element-binding protein (CREB)
      and its binding activity to DNA in the nuclear fraction from the adrenal medulla
      of cyclosporine-treated rats were much higher than that of the control rats.
      Calcineurin protein expression of cyclosporine-treated rats was less than that of
      the control rats. These results suggest that cyclosporine increased blood
      pressure via activation of the catecholamine synthetic pathway due to the
      activation of transcription factor CREB.

PMID- 11325025
TI  - Blood pressure and heart rate are increased by AF-DX 116, a selective M2
      antagonist, in autonomic imbalanced and hypotensive rats caused by repeated cold
      stress.
AB  - Rats exposed to SART (specific alternation of rhythm in temperature) stress,
      which are ideal animal models for vagotonia-type dysautonomia, show various
      changes in cardiac and circulatory systems. In this study, attention was directed
      to cholinergic function in the SART-stressed rat heart and the effects of AF-DX
      116, a specific muscarinic M2 antagonist, on blood pressure and heart rate. The
      results were compared with those obtained for atropine and pirenzepine. In SART
      stressed rats, systolic and diastolic blood pressures (SBP and DBP) were lower
      than in unstressed rats. Oral AF-DX 116 resulted in greater elevation of DBP than
      SBP in unstressed rats. In stressed rats, greater and more prolonged elevation of
      SBP than in unstressed rats was noted, particularly at higher doses. A dose
      dependent SBP change in stressed rats, caused by intravenous AF-DX 116, was
      shifted upward in parallel with that in unstressed groups, unlike with oral
      administration. The positive chronotropic effect of this drug was smaller in
      stressed rats than in unstressed rats, in contrast to the pressor effect. SART
      stressed rats may thus have an enhanced sympathetic tone in the heart, as well as
      changes in muscarinic M2 receptors at sympathetic nerve endings and at the heart
      muscle. The effects of AF-DX 116 on blood pressure and heart rate thus may arise
      from peripheral action and AF-DX 116 may be useful for treating hypotension
      related to autonomic imbalance of the vagotonia type.

PMID- 11325026
TI  - Presence of aldose reductase inhibitors in tea leaves.
AB  - Water extract from commercial English tea has a potent inhibitory activity
      against human placenta aldose reductase (NADPH oxidoreductase, E.C.1.1.1.21.).
      Inhibitory activity was separated into five major fractions by one-step
      chromatography with a C-18 reverse phase column. The most active fraction was
      further subjected to reverse phase column chromatography. As a result, a well
      known flavone-glycoside, isoquercitrin, was isolated as the most potent chemical.
      The inhibitory character of isoquercitrin for aldose reductase was a mix of
      uncompetitive and noncompetitive inhibitions, and its IC50 was 1 x 10(-6) M. In
      rat sciatic nerve tissue preparations, sorbitol accumulation in the presence of
      high concentrations of glucose (30 mM) was inhibited by 38% at 5 x 10(-4) M of
      isoquercitrin. The flavone-glycoside isoquercitrin is the active inhibitor of
      aldose reductase inhibitor present in English tea. Given the ability of aldose
      reductase inhibitors to prevent diabetic complications, an epidemiological study
      of the effect of tea consumption on the pathogenesis and progression of diabetic
      complications would be interesting.

PMID- 11325027
TI  - Comparison of noradrenergic and serotonergic antidepressants in reducing
      immobility time in the tail suspension test.
AB  - We examined the effects of two noradrenergic tricyclic antidepressants and two
      selective serotonin re-uptake inhibitors in the tail suspension test, with a
      suspension period of 30 min instead of the usual 10 min. Within the first 10 min,
      desipramine, nortriptyline and fluvoxamine significantly reduced the duration of
      immobility. Whereas desipramine and nortriptyline were also efficacious in the
      rest of the test period, fluvoxamine was not. Fluoxetine showed no significant
      effect throughout the study period. These results suggest that a prolonged tail
      suspension test results in functional changes in the noradrenergic and
      serotonergic systems and alters the sensitivity to antidepressants.

PMID- 11325028
TI  - Utilization of telemetry system to assess the cardiovascular profile of AH-1058,
      a new cardioselective Ca2+ channel blocker, in conscious dogs.
AB  - Cardiovascular effects of a new Ca2+ channel blocker AH-1058, 4-(5H
      dibenzo[a,d]cyclo-hepten-5-ylidene)-1-[(E)-3-(3-methoxy-2-nitro)phenyl-2
      propenyl]piperidine hydrochloride, were assessed in conscious dogs using a new
      telemetry system. AH-1058 (0.03, 0.1 and 0.3 mg/kg, i.v.) reduced systolic blood
      pressure and the maximal upstroke velocity of the left ventricular pressure and
      increased the heart rate in a dose-dependent manner without affecting the
      diastolic blood pressure; each of these responses lasted for several hours. These
      results support the previous knowledge that AH-1058 is a long-lasting
      cardiodepressive drug. The telemetry system provided important information for
      predicting favorable clinical effects of AH-1058.

PMID- 11325029
TI  - Antinociceptive effect of vitamin K2 (menatetrenone) in diabetic mice.
AB  - The antinociceptive effect of vitamin K2 (menatetrenone) in diabetic mice was
      examined using a tail-pressure test. Intraperitoneal injection of menatetrenone
      (10-100 mg/kg) produced a dose-dependent increase in the nociceptive threshold in
      diabetic mice. There was no significant difference between non-diabetic and
      diabetic mice in the menatetrenone-induced changes in the nociceptive threshold.
      The results suggest the therapeutical usefulness of menatetrenone for treating
      painful diabetic neuropathy and osteoporosis.

PMID- 11325030
TI  - Liposomal formulations of Cyclosporin A: a biophysical approach to
      pharmacokinetics and pharmacodynamics.
AB  - There are about 20 publications about liposomal formulations of Cyclosporin A
      (CyA) in the pharmaceutical and preclinical literature. Liposomal formulations
      were developed in order to reduce the nephrotoxicity of CyA and to increase
      pharmacological effects. However, conflicting results have been published as to
      the therapeutic properties of these formulations. This is also true for the
      change in pharmacokinetics and organ distribution of the liposomally encapsulated
      CyA as compared to conventionally formulated CyA. Using biophysical methods, it
      could be shown that CyA is not tightly entrapped in liposomal membranes, despite
      its high lipophilicity. CyA shows retardation only at high lipid concentrations
      in blood, following a massive injection of liposomes. This effect may diminish
      nephrotoxicity, as could be demonstrated by in vitro studies using a model tubule
      system. The results of these studies can be used to predict the formulation
      behavior in vivo and to optimize liposomal formulations. When applied in an early
      phase of the drug formulation process, these types of biophysical experiments can
      also help minimize animal experiments. However, these basic interaction studies
      cannot cover all physiological, pharmacological, and toxic effects in animals and
      humans.

PMID- 11325031
TI  - Preparation of drug delivery systems using supercritical fluid technology.
AB  - Small changes in temperature and pressure near the critical region induce
      dramatic changes in the density and solubility of supercritical fluids, thereby
      facilitating the use of environmentally benign agents such as CO2 for their
      solvent and antisolvent properties in processing a wide variety of materials.
      While supercritical fluid technologies have been in commercial use in the food
      and chromatography industries for several years, only recently has this
      technology made inroads in the formulation of drug delivery systems. This review
      summarizes some of the recent applications of supercritical fluid technology in
      the preparation of drug delivery systems. Drugs containing polymeric particles,
      plain drug particles, solute-containing liposomes, and inclusion complexes of
      drug and carrier have been formulated using this technology. Also, polymer
      separation using this technology is enabling the selection of a pure fraction of
      a polymer, thereby allowing a more precise control of drug release from polymeric
      delivery systems.

PMID- 11325032
TI  - Insulin self-association and the relationship to pharmacokinetics and
      pharmacodynamics.
AB  - The treatment of type 1 diabetes requires multiple, daily injections of insulin.
      While many improvements involving formulation adjustments have been made in an
      attempt to optimize therapy, clinical experience indicates that the commercially
      available insulin preparations used for treatment have significant limitations.
      One principal deficiency relates to poor simulation of the physiological insulin
      secretion pattern, making achieving normalization of blood glucose concentrations
      difficult. Endogenous insulin secretion in nondiabetic subjects is characterized
      by a pulsatile profile that displays multiple, meal-stimulated phases and low
      basal concentrations between meals and overnight. Optimal diabetes therapy,
      therefore, requires insulin preparations that display a rapid onset of action
      with corresponding rapid clearance to provide for meal ingestion as well as
      preparations that can maintain a sustained, peakless profile for basal
      requirements. Recent efforts in pharmaceutical research have used the concept of
      rational-based design of the insulin molecule in an attempt to produce
      preparations that display more ideal pharmacological profiles. Using detailed
      structural information obtained from X-ray crystallographic studies to guide
      design strategies and exploit the nonrestrictive synthetic capabilities of
      recombinant DNA technology, researchers have prepared a number of insulin analogs
      that display a reduced propensity towards self-association. Clinical evaluations
      have shown that these so called "monomeric" analogs better mimic the meal
      stimulated pharmacokinetics of insulin secretion observed in nondiabetics. Two
      monomeric insulin analog preparations have successfully obtained regulatory
      approval and are now commercially available. Efforts to produce optimized basal
      acting insulin analogs have lagged behind. While some of these analogs have been
      engineered using recombinant DNA technology, design strategies in many cases
      exploit physicochemical properties of insulin other than self-association. One
      basal insulin analog has recently received regulatory approval. This paper
      reviews insulin self-association and its relationship to pharmacokinetics and
      pharmacodynamics. Particular emphasis is placed on the approaches used to
      manipulate self-assembly resulting in meal-time insulin analogs that display
      optimal pharmacological properties. Other design strategies used to develop
      improved basal insulin preparations are also considered.

PMID- 11325033
TI  - Structure and function of S-adenosylhomocysteine hydrolase.
AB  - In mammals, S-adenosylhomocysteine hydrolase (AdoHcyase) is the only known enzyme
      to catalyze the breakdown of S-adenosylhomocysteine (AdoHcy) to homocysteine and
      adenosine. AdoHcy is the product of all adenosylmethionine (AdoMet)-dependent
      biological transmethylations. These reactions have a wide range of products, and
      are common in all facets of biometabolism. As a product inhibitor, elevated
      levels of AdoHcy suppress AdoMet-dependent transmethylations. Thus, AdoHcyase is
      a regulator of biological transmethylation in general. The three-dimensional
      structure of AdoHcyase complexed with reduced nicotinamide adenine dinucleotide
      phosphate (NADH) and the inhibitor (1'R, 2'S, 3'R)-9-(2',3'-dihyroxycyclopenten-1
      yl)adenine (DHCeA) was solved by a combination of the crystallographic direct
      methods program, SnB, to determine the selenium atom substructure and by treating
      the multiwavelength anomalous diffraction data as a special case of multiple
      isomorphous replacement. The enzyme architecture resembles that observed for NAD
      dependent dehydrogenases, with the catalytic domain and the cofactor-binding
      domain each containing a modified Rossmann fold. The two domains form a deep
      active site cleft containing the cofactor and bound inhibitor molecule. A
      comparison of the inhibitor complex of the human enzyme and the structure of the
      rat enzyme, solved without inhibitor, suggests that a 17 degrees rigid body
      movement of the catalytic domain occurs upon inhibitor/substrate binding.

PMID- 11325034
TI  - PU.1/Interferon Regulatory Factor interactions: mechanisms of transcriptional
      regulation.
AB  - The complexity of eukaryotic gene regulation is slowly being resolved. What has
      become clear is that transcriptional regulation is a multi-step process that
      involves the assembly of macromolecular complexes. This review will discuss the
      biology of the ETS family transcription factor PU.1, with emphasis on its
      interactions with two members of the Interferon Regulatory Factor (IRF) family,
      interferon consensus sequence binding protein (ICSBP), and IRF-4. The role of
      these interactions in transcriptional regulation is discussed, with respect to
      DNA binding motifs, protein-protein interaction and phosphorylation states that
      modulate PU.1/IRF interactions. Furthermore, potential transcriptional mechanisms
      for several genes are discussed, focusing on genes involved in innate immunity.
      Data from these studies suggest at least four distinct paradigms for
      transcriptional regulation by an ETS protein in conjunction with either ICSBP or
      IRF-4. These paradigms may describe regulatory mechanisms common to many distinct
      transcription factor families. Last, recent data from several laboratories have
      now documented the expression of ICSBP and IRF-4 in a range of cell types. These
      data suggest that ICSBP and IRF-4 may serve functions within these cell types
      that are distinct from their previously recognized functions.

PMID- 11325035
TI  - Thermodynamic molecular switch in macromolecular interactions.
AB  - It is known that most living systems can live and operate optimally only at a
      sharply defined temperature, or over a limited temperature range, at best, which
      implies that many basic biochemical interactions exhibit a well-defined Gibbs
      free energy minimum as a function of temperature. The Gibbs free energy change,
      deltaG(o) (T), for biological systems shows a complicated behavior, in which
      deltaG(o)(T) changes from positive to negative, then reaches a negative value of
      maximum magnitude (favorable), and finally becomes positive as temperature
      increases. The critical factor in this complicated thermodynamic behavior is a
      temperature-dependent heat capacity change (deltaCp(o)(T) of reaction, which is
      positive at low temperature, but switches to a negative value at a temperature
      well below the ambient range. Thus, the thermodynamic molecular switch determines
      the behavior patterns of the Gibbs free energy change, and hence a change in the
      equilibrium constant, Keq, and/or spontaneity. The subsequent, mathematically
      predictable changes in deltaH(o)(T), deltaS(o)(T), deltaW(o)(T), and deltaG(o)(T)
      give rise to the classically observed behavior patterns in biological reactivity,
      as demonstrated in three interacting protein systems: the acid dimerization
      reaction of alpha-chymotrypsin at low pH, interaction of chromogranin A with the
      intraluminal loop peptide of the inositol 1,4,5-triphosphate receptor at pH 5.5,
      and the binding of L-arabinose and D-galactose to the L-arabinose binding protein
      of Escherichia coli. In cases of protein unfolding of four mutants of phage T4
      lysozyme, no thermodynamic molecular switch is observed.

PMID- 11325036
TI  - Symposium: downstream from topoisomerase-DNA lesions: life-or-death consequences
      for the cell.

PMID- 11325037
TI  - How do drug-induced topoisomerase I-DNA lesions signal to the molecular
      interaction network that regulates cell cycle checkpoints, DNA replication, and
      DNA repair?
AB  - Recent results suggest that potentially lethal DNA lesions may result when
      replication forks encounter trapped topoisomerase-DNA complexes or some other
      types of DNA damage. Such events produce what are called replication-encounter
      lesions. These lesions have the characteristic that they may allow single
      stranded DNA-associated replication protein A (RPA) to become juxtaposed to dsDNA
      end-associated DNA-protein kinase. Our results suggest that DNA-protein kinases
      may then hyperphosphorylate the RPA2 subunit. We discuss a possible pathway by
      which hyperphosphorylation of RPA2 could lead to the release of active p53. This
      could constitute a pathway for signaling the presence of replication-encounter
      lesions to the p53-dependent cell cycle arrest and/or apoptosis initiator
      systems.

PMID- 11325038
TI  - Signal transduction pathways leading to cell cycle arrest and apoptosis induced
      by DNA topoisomerase poisons.
AB  - In this overview, I have summarized the important pathways of stress-induced
      signal transduction: stabilization and activation of p53 playing a central role
      in stress-induced cell cycle checkpoint and apoptosis, and activation of ASK1
      JNK/p38 pathway often induced by a variety of stress stimuli, which appears to be
      essentially required for apoptosis to follow.

PMID- 11325039
TI  - The physiology of p16(INK4A)-mediated G1 proliferative arrest.
AB  - Phosphorylation of the product of the retinoblastoma susceptibility gene (Rb)
      physiologically inactivates its growth-suppressive properties. Rb phosphorylation
      is mediated by cyclin-dependent kinases (CDKs), whose activity is enhanced by
      cyclins and inhibited by CDK inhibitors. p16(INK4A) is a member of a family of
      inhibitors specific for CDK4 and CDK6. p16(INK4A) is deleted and inactivated in a
      wide variety of human malignancies, including familial melanomas and pancreatic
      carcinoma syndromes, indicating that it is an authentic human tumor suppressor.
      Although one mechanism for its tumor suppression may be prevention of Rb
      phosphorylation, thereby causing G1 arrest, many normal cell types express
      p16(INK4A), and are still able to traverse the cell cycle. In a search for other
      mechanisms, we have found that p16(INK4A) is required for p53-independent G1
      arrest in response to DNA-damaging agents, including topoisomerase I and II
      inhibitors. Thus, like other tumor suppressors, p16(INK4A) plays an essential
      role in a DNA-damage checkpoint that leads to cell cycle arrest.

PMID- 11325040
TI  - Topoisomerase IIalpha mediates E2F-1-induced chemosensitivity and is a target for
      p53-mediated transcriptional repression.
AB  - Mutations of the retinoblastoma tumor suppressor, pRb, or its cyclin-cyclin
      dependent kinase (CDK) regulatory kinases or CDK inhibitors, allows unrestrained
      E2F activity, leading to unregulated cell cycle progression. However,
      overexpression of E2F-1 also sensitizes cells to apoptosis, suggesting that
      targeting this pathway may be of therapeutic benefit. Enforced expression of E2F
      1 in interleukin-3-dependent myeloid cells led to preferential sensitivity to the
      topoisomerase II inhibitor, etoposide, which was independent of p53 accumulation.
      Pretreatment of the E2F-1-expressing cells with ICRF-193, a second topoisomerase
      II inhibitor that does not cause DNA damage, protected these cells against
      etoposide-induced apoptosis. However, ICRF-193 cooperated with other DNA-damaging
      agents to induce apoptosis. Enforced expression of E2F-1 led to accumulation of
      p53 protein. An E2F-1 mutant that is defective in inducing cell cycle progression
      also induced p53, suggesting that p53 was responding directly to E2F, and not to
      secondary events caused by inappropriate cell cycle progression (i.e., DNA
      damage). Thus, topoisomerase II inhibition and DNA damage cooperate to
      selectively induce apoptosis in cells that have mutations in the pRb pathway.

PMID- 11325041
TI  - p53 modulation of DNA topoisomerase IIalpha gene expression.

PMID- 11325042
TI  - Mechanistic and kinetic studies of inhibition of enzymes.
AB  - A graphical method for analyzing enzyme data to obtain kinetic parameters, and to
      identify the types of inhibition and the enzyme mechanisms, is described. The
      method consists of plotting experimental data as nu/(V0 - nu) vs 1/(I) at
      different substrate concentrations. I is the inhibitor concentration; V0 and nu
      are the rates of enzyme reaction attained by the system in the presence of a
      fixed amount of substrate, and in the absence and presence of inhibitor,
      respectively. Complete inhibition gives straight lines that go through the
      origin; partial inhibition gives straight lines that converge on the 1-I axis, at
      a point away from the origin. For competitive inhibition, the slopes of the lines
      increase with increasing-substrate concentration; with noncompetitive inhibition,
      the slopes are independent of substrate concentration; with uncompetitive
      inhibition, the slopes of the lines decrease with increasing substrate
      concentrations. The kinetic parameters, Km, Ki, Ki', and beta (degree of
      partiality) can best be determined from respective secondary plots of slope and
      intercept vs substrate concentration, for competitive and noncompetitive
      inhibition mechanism or slope and intercept vs reciprocal substrate concentration
      for uncompetitive inhibition mechanism. Functional consequencs of these analyses
      are represented in terms of specific enzyme-inhibitor systems.

PMID- 11325043
TI  - Localized exocytosis detected by spatially resolved amperometry in single
      pancreatic beta-cells.
AB  - Spatially resolved measurements of exocytosis in pancreatic beta-cells were made
      using amperometry with 1-microm radius electrodes. These measurements revealed
      that certain portions of a cell actively undergo exocytosis following stimulation
      with depolarizing agents, but other regions are inactive. The amperometric
      measurements were compared to measurements made with the membrane indicator dye,
      FM1-43, which showed uneven increases in fluorescence around the surface of the
      cell, with amperometric secretion being detected only at the brightest regions.
      In some instances, a large number of exocytotic events were detected from one
      electrode position. The number of events was larger than what would be expected
      based on the number of vesicles that could fit under an electrode of the
      dimensions used. These results suggest a mechanism of vesicle traffic that allows
      multiple fusions at a small membrane area.

PMID- 11325044
TI  - Role of modified nucleosides of yeast tRNA(Phe) in ribosomal binding.
AB  - Naturally occurring nucleoside modifications are an intrinsic feature of transfer
      RNA (tRNA), and have been implicated in the efficiency, as well as accuracy-of
      codon recognition. The structural and functional contributions of the modified
      nucleosides in the yeast tRNA(Phe) anticodon domain were examined. Modified
      nucleosides were site-selectively incorporated, individually and in combinations,
      into the heptadecamer anticodon stem and loop domain, (ASL(Phe)). The stem
      modification, 5-methylcytidine, improved RNA thermal stability, but had a
      deleterious effect on ribosomal binding. In contrast, the loop modification, 1
      methylguanosine, enhanced ribosome binding, but dramatically decreased thermal
      stability. With multiple modifications present, the global ASL stability was
      mostly the result of the individual contributions to the stem plus that to the
      loop. The effect of modification on ribosomal binding was not predictable from
      thermodynamic contributions or location in the stem or loop. With 4/5
      modifications in the ASL, ribosomal binding was comparable to that of the
      unmodified ASL. Therefore, modifications of the yeast tRNA(Phe) anticodon domain
      may have more to do with accuracy of codon reading than with affinity of this
      tRNA for the ribosomal P-site. In addition, we have used the approach of site
      selective incorporation of specific nucleoside modifications to identify 2'O
      methylation of guanosine at wobble position 34 (Gm34) as being responsible for
      the characteristically enhanced chemical reactivity of C1400 in Escherichia coli
      16S rRNA upon ribosomal footprinting of yeast tRNA(Phe). Thus, effective ribosome
      binding of tRNA(Phe) is a combination of anticodon stem stability and the correct
      architecture and dynamics of the anticodon loop. Correct tRNA binding to the
      ribosomal P-site probably includes interaction of Gm34 with 16S rRNA C1400.

PMID- 11325045
TI  - Nonnative intermediate state of acid-stable beta-sheet protein.
AB  - Cell adhesion molecule, CD2, from the immunoglobulin superfamily, is comprised of
      antibodies and Ig-like domains and plays a fundamental role, not only in the
      immune system, but also in the interactions between cells, specifically in cell
      cell adhesion. This study examines the N-terminal domain 1 of CD2 (CD2-1) at
      different pHs, and in 2,2,2-trifluoroethanol (TFE), using nears- and far-UV
      circular dichroism (CD), fluorescence, and 1H nuclear magnetic resonance to
      elucidate factors contributing to the Ig beta-structure. Contrary to the complete
      unfolding induced by guanidinehydrochloride, CD2-1 retains its native tertiary
      structure at pHs from 1.0 to 10.0. Like the effects of high temperatures that
      have previously been observed, TFE reduces the integrity of the tertiary
      structure, while reorganizing the secondary structure from a native all-beta
      sheet to a significantly alpha-helical conformation. The induced helicity of CD2
      1 correlates with the helicity inherent in its primary sequence. Our results
      suggest that electrostatic interactions are less important for the formation of
      the native secondary and tertiary structure of CD2-1, although they are crucial
      for CD2's adhesion function. Interference with the protein's hydrophobic
      interactions and hydrogen-bonding networks, however, causes significant changes
      in its conformation. Residues of CD2-1, with high conformational flexibility, may
      contribute for the formation of a metastable dimer by domain-swapping.

PMID- 11325046
TI  - Calcium signaling and annexins.
AB  - The annexins, are a family of calcium ion (Ca2+)-binding proteins whose
      physiological functions are poorly understood. Although many diverse functions
      have been proposed for these proteins, such as in vesicle trafficking, this
      review focuses on their proposed roles as Ca2+ or other ion channels, or as
      intracellular ion channel regulators. Such ideas are founded mainly on in vitro
      and structural analyses, but there is increasing evidence that at least some
      members of this protein family may indeed play a part in intracellular Ca2+
      signaling by acting both as atypical ion channels and as modulators of ion
      channel activity. This review first introduces the annexin family, then discusses
      intracellular localization, developmental regulation, and modes of membrane
      association of annexins, which suggest roles in Ca2+ homeostasis. Finally, it
      examines the structural and electrophysiological data that argue for key roles
      for annexins in the control of ion fluxes.

PMID- 11325047
TI  - Aminoglycoside antibiotics bound to aminoglycoside-detoxifying enzymes and RNA
      adopt similar conformations.
AB  - Conformations of ribostamycin and isepamicin, aminoglycoside antibiotics, bound
      to an aminoglycoside antibiotic, 3'-phosphotransferase, were determined by
      transferred nuclear Overhauser effect spectroscopy and molecular modeling. Two
      major conformers of enzyme-bound ribostamycin, a neomycin-group aminoglyeoside
      were observed. The 3'- and 5"-OH groups (reactive hydroxyl groups) in the
      conformers are placed in approximate locations. One of the conformers is similar
      to the structure of paromomycin bound to a 27-nucleotide piece of ribosomal RNA
      that represents the A-site of the small ribosomal subunit, where rings A and C
      are in an orthogonal arrangement. Isepamicin, a kanamycin-group aminoglycoside
      antibiotic, also showed two major enzyme-bound conformations. Both conformations
      were similar to those observed for bound isepamicin in the active site of an
      aminoglycoside(6')-acetyl transferase-Ii. Conformations of other RNA-bound
      kanamycin-group aminoglycosides were also similar to the enzyme-bound
      conformations of isepamicin. These observations suggest that aminoglycosides may
      adopt similar conformations when bound to RNA and protein targets. This may have
      significant implications in the design of enzyme inhibitors and/or antibiotics.

PMID- 11325048
TI  - Conformations of antibiotics in active sites of aminoglycoside-detoxifying
      enzymes.

PMID- 11325049
TI  - Noncovalent labeling of proteins in capillary electrophoresis with laser-induced
      fluorescence detection.
AB  - Interest in the use of capillary electrophoresis (CE) as a tool for protein
      separations continues to grow. Additionally, laser-induced fluorescence (LIF)
      detection schemes promise ultrasensitive detection of small quantities of these
      important biomolecules following their separation. In most cases, LIF detection
      of proteins necessitates their prior derivatization with a fluorescent label
      molecule. To minimize the amount of additional sample handling and time
      associated with such labeling procedures, not to mention the sometimes-stringent
      pH and temperature controls they require, noncovalent labeling is presented as a
      viable alternative. This review article considers established methods for
      noncovalent labeling of proteins for their subsequent analysis by CE-LIF. Label
      molecules suitable for excitation and emission in the ultraviolet, visible, and
      near-infrared regions of the spectrum are enumerated for a variety of protein
      analytes.

PMID- 11325050
TI  - Chromosome evolution in the Salmonidae (Pisces): an update.
AB  - The karyotypes of salmonid fishes including taxa in the three subfamilies
      Coregoninae, Thymallinae and Salmoninae are described. This review is an update
      of the (Hartley, 1987) review of the chromosomes of salmonid fishes. As described
      in the previous review, the karyotypes of salmonid fishes fall into two main
      categories based on chromosome numbers: the type A karyotypes have diploid
      numbers close to 80 with approximately 100 chromosome arms (2n = 80, NF = 100),
      and the type B karyotypes have diploid numbers close to 60 with approximately 100
      chromosome arms (2n = 60, NF = 100). In this paper we have proposed additional
      sub categories based on variation in the number of chromosome arms: the A' type
      with NF = 110-120, the A" type with NF greater than 140, and the B' type with NF
      less than 80. Two modes of chromosome evolution are found in the salmonids: in
      the Coregoninae and the Salmoninae the chromosomes have evolved by centric
      fusions of the Robertsonian type decreasing chromosome numbers (2n) while
      retaining chromosome arm numbers (NF) close to that found in the hypothetical
      tetraploid ancestor so that most extant taxa have either type A or type B
      karyotypes. In the Thymallinae, the chromosomes have evolved by inversions so
      that chromosome arm numbers (NF) have increased but chromosome numbers (2n) close
      to the karyotype of the hypothetical tetraploid ancestor have been retained and
      all taxa have type A' karyotypes. Most of the taxa with type B karyotypes in the
      Coregoninae and Salmoninae are members of the genus Oncorhynchus, although at
      least one example of type B karyotypes is found in all of the other genera. These
      taxa either have an anadromous life history or are found in specialized
      lacustrine environments. Selection for increases or decreases in genetic
      recombination as proposed by Qumsiyeh, 1994 could have been involved in the
      evolution of chromosome number in salmonid fishes.

PMID- 11325051
TI  - Ethylene signal perception and transduction: multiple paradigms?
AB  - Current progress on the mechanisms of ethylene signal perception and transduction
      are reviewed with an emphasis on reconciling data from molecular genetics and
      from biochemical approaches. It is proposed that there exist two or more
      interacting transduction pathways.

PMID- 11325052
TI  - From arctic lemmings to adaptive dynamics: Charles Elton's legacy in population
      ecology.
AB  - We shall examine the impact of Charles S. Elton's 1924 article on periodic
      fluctuations in animal populations on the development of modern population
      ecology. We argue that his impact has been substantial and that during the past
      75 years of research on multi-annual periodic fluctuations in numbers of voles,
      lemmings, hares, lynx and game animals he has contributed much to the
      contemporary understanding of the causes and consequences of population
      regulation. Elton was convinced that the cause of the regular fluctuations was
      climatic variation. To support this conclusion, he examined long-term population
      data then available. Despite his firm belief in a climatic cause of the self
      repeating periodic dynamics which many species display, Elton was insightful and
      far-sighted enough to outline many of the other hypotheses since put forward as
      an explanation for the enigmatic long-term dynamics of some animal populations.
      An interesting, but largely neglected aspect in Elton's paper is that it ends
      with speculation regarding the evolutionary consequences of periodic population
      fluctuations. The modern understanding of these issues will also be scrutinised
      here. In population ecology, Elton's 1924 paper has spawned a whole industry of
      research on populations displaying multi-annual periodicity. Despite the efforts
      of numerous research teams and individuals focusing on the origins of multi
      annual population cycles, and despite the early availability of different
      explanatory hypotheses, we are still lacking rigorous tests of some of these
      hypotheses and, consequently, a consensus of the causes of periodic fluctuations
      in animal populations. Although Elton would have been happy to see so much effort
      spent on cyclic populations, we also argue that it is unfortunate if this focus
      on a special case of population dynamics should distract our attention from more
      general problems in population and community dynamics.

PMID- 11325053
TI  - Sources and bioavailability of phosphorus fractions in freshwaters: a British
      perspective.
AB  - This paper seeks a perspective on the forms of phosphorus which promote aquatic
      eutrophication, with the particular quest of establishing their sources. A short
      background traces the development of understanding of nutrient enrichment and the
      suppositions about the relative contributions of agriculture, sewage and
      detergent residues. Most aquatic systems, and their primary producers, are
      naturally deficient in biologically-available phosphorus. Aquatic plants have
      evolved very efficient phosphorus uptake mechanisms. The biomass responses to an
      increase in the supply of phosphorus are stoichiometrically predictable. The most
      bioavailable forms of phosphorus are in solution, as orthophosphate ions, or are
      readily soluble or elutable from loose combinations. Ready bioavailability
      coincides well with what is measurable as molybdate-reactive (MRP) or soluble
      reactive phosphorus (SRP). Most other forms, including phosphates of the alkaline
      earth metals, aluminium and iron are scarcely available at all. Orthophosphate
      ions sorbed to metal oxides and hydroxides are normally not biologically
      available either, except through weak dissociation ('desorption'). The production
      of alkaline phosphatase provides organisms with an additional mechanism for
      accelerating the sequestration of phosphate from organic compounds. Bioavailable
      phosphate is liberated when redox- or alkali-sensitive metal hydroxides dissolve
      but these processes are minor contributors to the biological responses to
      nutrient enrichment. Most of the familiar eutrophication is attributable to the
      widespread application of secondary sewage treatment methods to the wastes
      emanating from a burgeoning and increasingly urbanised human population. The use
      of polyphosphate-based detergents, now in decline, has contributed to the
      problem. In aquatic systems, the additional phosphorus raises the biological
      supportive capacity, sometimes to the capacity of the next limiting factor
      (carbon, light, hydraulic retention or of another nutrient). At high
      orthophosphate loadings, the straight stoichiometric yield relationship between
      biomass yield and phosphorus a vailability is lost. Movements of phosphorus and
      its recycling within aquatic systems do not prevent the slow gravitation of
      phosphorus to the bottom substrata. The phosphorus retentivity of sediments
      depends upon their chemical composition. While oxide-hydroxide binding capacity
      in the surface sediments persists, they act as a sink for phosphorus and a
      control on further cycling. Iron-rich and clay-rich sediments perform best in
      these conditions; calcareous sediments least so. Eutrophication may lead to the
      exhaustion of sediment P-binding capacity. Non-sorbed phosphate is readily
      recyclable if primary producers have access to it. Recycling is most rapid in
      shallow waters (where sediment disturbance, by flow, by wind action and through
      bioturbation, is frequent and least in deep ventilated sediments. The
      contributions of phosphorus from catchments are assessed. The slow rate of
      weathering of (mostly apatitic) minerals, the role of chemical binding in soils
      and the incorporation and retentivity bv forested terrestrial ecosystems each
      contribute to the minimisation of phosphorus leakage to drainage waters.
      Palaeolimnological and experimental evidence confirms that clearance of land and
      ploughing its surface weakens the phosphorus retentivity of catchments. The
      phosphorus transferred from arable land to drainage remains dominated by sorbed
      fractions which are scarcely bioavailable. Some forms of intensive market
      gardening or concentrated stock rearing may mobilise phosphates to drainage but
      it is deduced that drainage from agricultural land is not commonly a major source
      of readily bioavailable phosphorus in water. Careful budgeting of the phosphates
      in run-off from over-fertilised soils may nevertheless show that a
      proportionately small loss of bioavailable phosphorus can still be highly
      significant in promoting aquatic plant production. The bioavailable-phosphorus
      (BAP) load achieving the OECD threshold of lake eutrophy (35 mg P m(-3)) is
      calculated to be equivalent to a terrestrial loss rate of approximately 17.5 kg
      BAP km(-2) year(-1)), or only 1-2% of a typical fertiliser application. The
      output is shown to be comparable with the P yield from secondary treatment of the
      sewage produced by a resident population of 30-44 persons km(-2). With tertiary
      treatment, the equivalence is with approximately 200 persons km(-2).

PMID- 11325054
TI  - Coincidence, coevolution, or causation? DNA content, cell size, and the C-value
      enigma.
AB  - Variation in DNA content has been largely ignored as a factor in evolution,
      particularly following the advent of sequence-based approaches to genomic
      analysis. The significant genome size diversity among organisms (more than 200000
      fold among eukaryotes) bears no relationship to organismal complexity and both
      the origins and reasons for the clearly non-random distribution of this variation
      remain unclear. Several theories have been proposed to explain this 'C-value
      enigma' (heretofore known as the 'C-value paradox'), each of which can be
      described as either a mutation pressure' or 'optimal DNA' theory. Mutation
      pressure theories consider the large portion of non-coding DNA in eukaryotic
      genomes as either 'junk' or 'selfish' DNA and are important primarily in
      considerations of the origin of secondary DNA. Optimal DNA theories differ from
      mutation pressure theories by emphasizing the strong link between DNA content and
      cell and nuclear volumes. While mutation pressure theories generally explain this
      association with cell size as coincidental, the nucleoskeletal theory proposes a
      coevolutionary interaction between nuclear and cell volume, with DNA content
      adjusted adaptively following shifts in cell size. Each of these approaches to
      the C-value enigma is problematic for a variety of reasons and the preponderance
      of the available evidence instead favours the nucleotypic theory which postulates
      a causal link between bulk DNA amount and cell volume. Under this view, variation
      in DNA content is under direct selection via its impacts on cellular and
      organismal parameters. Until now, no satisfactory mechanism has been presented to
      explain this nucleotypic effect. However, recent advances in the study of cell
      cycle regulation suggest a possible 'gene nucleus interaction model' which may
      account for it. The present article provides a detailed review of the debate
      surrounding the C-value enigma, the various theories proposed to explain it, and
      the evidence in favour of a causal connection between DNA content and cell size.
      In addition, a new model of nucleotypic influence is developed, along with
      suggestions for further empirical investigation. Finally, some evolutionary
      implications of genome size diversity are considered, and a broadening of the
      traditional 'biological hierarchy' is recommended.

PMID- 11325055
TI  - Proline-rich synapse-associated protein-1/cortactin binding protein 1
      (ProSAP1/CortBP1) is a PDZ-domain protein highly enriched in the postsynaptic
      density.

PMID- 11325056
TI  - The nature and function of mononuclear cells on the resorbed surfaces of bone in
      the reversal phase during remodeling.
AB  - In a reversal phase of bone remodeling many mononuclear cells appear on the
      resorbed surfaces of bone with characteristic reversal lines as revealed by
      transmission electron microscopy (TEM). However, these mononuclear cells have
      been variously hypothesized or reported. The present study examined the TEM
      features on the resorbed surfaces of three calcified connective tissues, and
      aimed to clarify the nature and function of the mononuclear cells in a reversal
      phase. Dentine slices cultured with isolated osteoclasts, human deciduous teeth,
      and rat mandibles were used in this study. Specimens were fixed, decalcified, and
      then embedded in Epon 812, and sectioned into 0.1-microm-thick ultrathin
      sections. The ultrathin sections were stained with uranyl acetate and lead
      citrate, and then examined by TEM. Many sharply pointed collagen fibrils with
      striation were observed exposed on the resorbed surfaces of cultured dentine
      slices, but there were neither cells nor reversal lines. The same features were
      observed on the root dentine surfaces of human deciduous teeth. Under many
      mononuclear cells in a reversal phase of remodeling, reversal lines were seen on
      the resorbed surfaces of rat mandibles, but there were no striated collagen
      fibrils exposed on the bone surfaces. The alternation of the TEM features on the
      resorbed surfaces before and after the participation of mononuclear cells in a
      reversal phase of remodeling suggests the nature and function of these cells:
      they participate in both degrading the demineralized and disrupted matrix left on
      the resorbed surfaces and forming reversal lines there.

PMID- 11325057
TI  - Histochemical analyses of glycosaminoglycans in the synovial membrane of the
      canine knee joint.
AB  - The accurate localization and nature of glycosaminoglycans in the synovial
      membrane of the canine knee joint were examined histochemically by means of the
      selective sensitized diamine procedures based upon high and low iron diamine
      stainings in combination with enzyme digestions. Using these methods, it was
      possible to clearly and easily detect exceedingly small amounts of
      glycosaminoglycans in synovial tissues, which cannot be visualized by methods
      employed to date. The sensitized high iron diamine (S-HID) procedure resulted in
      positive reactions of varying intensities in the intercellular matrix of synovial
      intima, and in the extracellular matrix and small capillary walls of the
      superficial layer in the synovial subintima, and also reacted vividly in the
      extracellular matrix and blood vessel walls of the deeper layer in the synovial
      subintima. In particular, the sensitized low iron diamine (S-LID) procedure
      resulted in positive reactions of the extracellular matrix in the synovial
      subintimal layers. The S-HID and S-LID procedures combined with the enzyme
      digestions proved that glycosaminoglycan molecular species such as chondroitin
      sulfate A/C, dermatan sulfate, heparan sulfate and hyaluronic acid are present in
      various concentrations in the synovial membrane of the canine knee joint. The
      present results were discussed with reference to the histophysiological and
      pathophysiological functions of glycosaminoglycans in the synovium of domestic
      mammals.

PMID- 11325058
TI  - The initial attachment of cemental fibrils to the root dentin surface in
      acellular and cellular cementogenesis in rat molars.
AB  - To elucidate the initial attachment mechanism of cemental fibrils to the root
      dentin surface in acellular and cellular cementogenesis, developing rat molars
      were observed by light microscopy and scanning electron microscopy combined with
      NaOH maceration. The NaOH maceration was used to observe details of the
      positional association of cemental and dentinal fibrils during cementogenesis. An
      initial hematoxylin stained, cementum layer began to form on the root dentin
      surface with the first dentin mineralization in both acellular and cellular
      cementogenesis. The initial attachment of cemental fibrils to the dentin surface
      also began at this point. At the initial attachment the intermingling of cemental
      and dentinal fibrils occurred only in places. With advanced cementogenesis the
      initial cementum layer became the fibril-poor cemento-dentinal junction. This
      suggests that cemental fibrils attach on the initial cementum layer, and not
      directly on dentinal fibrils, so that the layer results in the fibril-poor
      cemento-dentinal junction. The present study suggests that an intervening
      adhesive is necessary for the cemento-dentinal attachment at any stage of
      cementogenesis in rat molars.

PMID- 11325059
TI  - Immunohistochemical localization of the neural cell adhesion molecule in the rat
      sciatic nerve.
AB  - The neural cell adhesion molecule (NCAM) has been widely studied in the early
      embryonal development of the nervous system. The data about NCAM distribution in
      the peripheral nerves during postnatal life are scant and some controversial. In
      the present study, the NCAM localization in the sciatic nerves of 15-day-old
      Wistar rats has been studied. Semi-thin sections of the nerves were immunotested
      with a polyclonal antibody (Santa Cruz Biotechnology) that recognizes rat NCAM.
      The antibody was visualized with donkey anti-goat IgG, conjugated to 12 nm
      colloidal gold, and silver amplification. In the myelinated nerve fibres, the
      immunoreactivity was associated with the axons, mainly with their plasma
      membrane, which was unstained in the nodes of Ranvier. The myelin sheaths and the
      myelinating Schwann cells were negative. The extracellular matrix and the bundles
      of non-myelinated nerve fibres were immunopositive.

PMID- 11325060
TI  - Light and electron microscopic investigation of the lectin-binding pattern in the
      oxyntic gland region of bovine abomasum.
AB  - For the first time the expression of glycoconjugate residues in the oxyntic gland
      region of bovine abomasum has been investigated by means of lectin
      histochemistry. For light microscopic investigations, a battery of ten lectins,
      Con A, PSA, UEA I, WGA, LEA, SNA, RCA120, MPA, DBA and SBA was used. For electron
      microscopic examinations, WGA and RCA120 were utilized. The staining pattern of
      the lectins in all exocrine cell types of the oxyntic gland region is described.
      Compared to the results of monogastric species our study reveals some
      similarities, but just as many differences in the composition of glycoconjugate
      residues in bovine exocrine cell types. Typical for surface mucous cells is the
      amount of L-fucose, N-acetyl glucosamine residues and Galbeta1, 4GlcNAc sequences
      in the secretory granules. SNA could serve as a marker for surface mucous cells,
      because this lectin exclusively stains the plasma membrane and the secretory
      granules of surface mucous cells and the extracellular mucus. L-fucose and N
      acetyl glucosamine are typical for the secretory granules of mucous neck cells.
      In addition, the secretory granules show the highest amount of N-acetyl
      galactosamine residues of all exocrine cells, so that DBA and SBA are recommended
      as marker lectins for mucous neck cells. Most lectins strongly stain the
      intracellular membrane system of oxyntic cells. The cocktail of glycoconjugates
      in the vicinity of the HCI production site provide protection against chemical
      injury. In chief cells only the apical plasma membrane is more or less labeled
      with all lectins apart from SNA. Specific marker lectins for oxyntic cells or
      chief cells of the bovine have not been characterized.

PMID- 11325061
TI  - On biomechanical properties of the sacroiliac joint in purebred dogs.
AB  - Relative to the Yorkshire Terriers and Maltese dogs the mean expected sacroiliac
      joint load was calculated to be 1.4-1.6 times higher in other small breeds and
      1.7-2.7 times higher in large breeds. The statistically significantly different
      (p < 0.01, p < 0.001) and mechanically less efficient inclination angles of the
      wings of the sacrum in adult large breeds (especially German Shepherd Dogs)
      suggest even higher forces acting on their sacroiliac ligaments. Unlike the case
      in small breeds, the sacral auricular surface was concave in large dogs to
      improve interlocking between sacrum and ilium and to reduce craniocaudal
      translation. An additional ossification center forming the ventral aspect of the
      transverse process of the second sacral vertebra was present in large breeds,
      occasionally in midsized and small, but never in toy breeds. This and the
      relationship between age and inclination angles of the wings of the sacrum in
      juvenile specimens indicate an affection of the three-dimensional modeling of the
      wings of the sacrum by formative stimuli such as body weight and locomotion.

PMID- 11325062
TI  - Breed specific osteological features of the canine lumbosacral junction.
AB  - Inefficient facet geometry suggests the lumbosacral junction to be mechanically
      imperfect in a large number of dogs (especially German Shepherd Dogs) resulting
      in a significantly higher prevalence of osteophyte formation and increase in the
      longitudinal extension of the articular surface covering the caudal articular
      process of the seventh lumbar vertebra. Such osteological features give evidence
      for lumbosacral craniocaudal translation, were predominantly noticed in
      combination with axial rotation and are taken to be anatomic risk factors that
      can predispose to the development of lumbosacral stenosis. The statistically
      significant relationship between age and the magnitude of the caudal facet
      inclination angles of the seventh lumbar vertebra in juvenile specimens indicate
      an affection of the three-dimensional modeling of the immature caudal articular
      processes by formative stimuli such as body weight and locomotion. However,
      results additionally indicate an association between the magnitude of these
      inclination angles and vertebral body dimensions also suggesting a congenital
      influence on facet geometry.

PMID- 11325063
TI  - Microtubules and vimentin associated filaments (VIFs) in cultured human gingival
      fibroblasts (HGFs) after exposure to acrolein and acetaldehyde.
AB  - Tobacco smoke, particularly its non-volatile fraction e. g. nicotine, is
      considered to be a major risk factor for the development and progression of
      periodontal disease. The purpose of this study has been to determine the effects
      of acrolein and acetaldehyde of the volatile fraction of tobacco smoking, on
      human gingival fibroblasts (HGFs) cultured in vitro with particular attention to
      cytoskeletal structures. A human gingival fibroblast strain derived from healthy
      gingiva was utilized in this study. The cells were exposed to acrolein and
      acetaldehyde at various concentrations. Control and treated cells were compared
      as regards their adhesion on cell culture dishes. Their cytoskeletal structures
      [tubulin and vimentin intermediate filaments (VIFs)] were examined by
      fluorescence microscopy. The results revealed that both substances produced
      similar effects resulting in a dose dependent decrease in cell adhesion and
      alterations of HGF cytoskeleton consisting of rearrangement and/or disruption of
      microtubules and vimentin associated filaments. Changes in cell shape and
      decrease in cell size were also seen. On the basis of this in vitro study, it
      appears that tobacco, through its volatile components, may directly affect the
      main functions of HGFs.

PMID- 11325064
TI  - The cartilage of the third eyelid: a comparative macroscopical and histological
      study in domestic animals.
AB  - The purpose of this comparative study was to evaluate morphological differences
      between the cartilages of the third eyelid in dogs, cats, pigs, cows, small
      ruminants and horses. For that reason a total of 83 third eyelids were
      investigated. By the aid of a modified maceration technique, the three
      dimensional form of the cartilage could be demonstrated for the first time.
      Generally, the cartilage consists of a long narrow appendix which is followed by
      a variable crossbar. In dogs the appendix is cone shaped in the basal end and
      extends to form a triangular plate. The former is crescent-like in shape and has
      a marked bulge. The cartilage of the cat consists of an appendix which is
      enlarged in the proximal end as compared to the dog. The crossbar resembles a
      reverse s-form with ends tapering off to a point. In contrast pig and cow
      cartilage possess a typical anchorform whereas the cartilage of small ruminants
      starts with a thin rod which extends in a slightly curved form ending in an oval
      plate. The crossbar is crescent-like in these animals. In the horse the base of
      the cartilage is surrounded by a massive fatty tissue and the crossbar has a
      characteristic hook-form. Moreover, there are significant differences in regard
      to the quality of the cartilage, especially concerning the presence and
      distribution of elastic fibres. In cats and horses the elastic fibres of the
      adjacent connective tissue penetrate the perichondrium. Additionally, the centre
      of the cartilage shows a very dense network consisting of fine elastic fibres. In
      dogs, pigs, cows and small ruminants the cartilage consists of hyaline quality
      and only in the neighbouring connective tissue are some elastic fibres
      detectable.

PMID- 11325065
TI  - Heart biometry and allometry in rats submitted to nitric oxide synthesis blockade
      and treatment with antihypertensive drugs.
AB  - Fifty mature male rats were separated into groups of ten rats each (control, L
      NAME, spironolactone, enalapril and verapamil). On the 41st day of
      experimentation, animals were anesthetized, weighed and sacrificed. The tail
      blood pressure (TBP) was 76% higher in L-NAME group than in the control group.
      Spironolactone, enalapril and verapamil were efficient in reducing TBP in those
      respective groups of rats (spironolactone was less efficient in reducing TBP).
      The heart mass/body mass ratio (HBR) increased 24% in L-NAME group and
      spironolactone group. No differences in HBR were found when control animals and
      animals treated with enalapril and verapamil were compared. Heart volume (HV) was
      greater in L-NAME group than other groups, but it was not different comparing the
      L-NAME and the spironolactone groups. The left ventricle was responsible for the
      changes in the HV. The relationship between the HV and the body mass (BM) was not
      significant in the groups L-NAME and spironolactone. However, this relationship
      was significant and allometric in control, enalapril and verapamil groups. In
      control group, HV had a positive allometric tendency against the BM, but in the
      enalapril and verapamil groups this tendency was allometrically negative. Cardiac
      hypertrophy in rats under inhibition of NO synthesis was prevented by treatment
      with enalapril and verapamil more efficiently than spironolactone.

PMID- 11325066
TI  - The effect of stomach volume on the colon topography in cats.
AB  - The aim of this study has been to describe the effect of varying degrees of
      fullness of the stomach on the topography of colon in cats by means of the
      sectional anatomy of the abdominal cavity. Twenty-four adult healthy cats of both
      sexes and of different ages were used. The cats were divided into two groups, of
      which group one had empty stomachs and the second filled stomachs. Eight cats
      were dissected. The remaining cats were frozen at -20 degrees C, the eight of
      which were sectioned paramedially and the other eight transversely. The ascending
      colon started at the level of the fifth lumbar vertebra, and the cranial boundary
      of the transverse colon was at the level of the second lumbar vertebra in cats
      with empty stomachs. The ascending colon started at the level of the sixth lumbar
      vertebra in cats with full stomachs, while the cranial boundary of the transverse
      colon was at the level of the fourth lumbar vertebra and had lost relationship to
      the right kidney resting directly on the vertebral column. In both groups, the
      descending colon was located in the left abdominal cavity up to the level of the
      sixth lumbar vertebra, at which point it curved medially and ran cranial to the
      seventh lumbar vertebra in the median plane. Results from this study are to throw
      light on computed tomography and magnetic resonance imaging.

PMID- 11325067
TI  - Radial sesamoid bone as a part of the manipulation system in the lesser panda
      (Ailurus fulgens).
AB  - The well-developed radial sesamoid bone presented a rod-like shape in the lesser
      panda. It could be separated into two components: (1) an ulnar cartilaginous, (2)
      a radial osseous part. The radial sesamoid bone was connected with four elements
      as follows: (1) the tendon of the M. abductor pollicis longus, (2) M. abductor
      pollicis brevis and M. opponens pollicis, (3) Aponeurosis palmaris, and (4)
      Flexor retinaculum. The bone made no articulation with the first metacarpal. The
      movement of the radial sesamoid bone may be controlled by the connecting muscles
      and muscle-related structures. It is suggested that the bone acts as a supporting
      ridge in the gripping action in the lesser panda. However, we suggest that the
      grasping mechanism is obviously different from that of the giant panda, in which
      the radial sesamoid bone is connected strongly with the first metacarpal.

PMID- 11325068
TI  - Lack of association between genetic polymorphism of CYP11B2 and hypertension in
      Japanese: the Suita Study.
AB  - Aldosterone synthase (CYP11B2) is a key enzyme in the biosynthesis of
      aldosterone. Recently, a polymorphism in the 5'-flanking region of the CYP11B2
      gene [T(-344)C] has been reported to be associated with blood pressure and plasma
      aldosterone levels. We investigated the association between this polymorphism and
      hypertension in a large population-based sample of 4,000 Japanese. The genotype
      distribution in hypertensive subjects (n=1,535) was compared to that in
      normotensive subjects (n=2,514). In subjects not receiving antihypertensive
      medication, the influence of the genotype on blood pressure values adjusted for
      clinical covariates was analyzed. All analyses were performed separately for men
      and women. The genotype distribution did not differ between hypertensive and
      normotensive subjects in either men (frequency of C allele: 30.3% vs. 31.4%,
      p=0.48) or women (31.5% vs. 31.7%, p=0.93). There were no significant differences
      in systolic blood pressure, diastolic blood pressure, or pulse pressure among the
      three genotypes in either men or women who had not received hypertensive
      medication. Our data suggest that the T(-344)C polymorphism of CYP11B2 is
      unlikely to influence blood pressure status in the Japanese population.

PMID- 11325069
TI  - The circadian blood pressure rhythm in non-diabetic hemodialysis patients.
AB  - This study investigates the circadian blood pressure variation of non-diabetic
      chronic hemodialysis (HD) patients on both HD and non-HD days as well as the
      factors affecting diurnal BP variation. Forty-nine HD patients aged 61.8 +/- 12.9
      years who were on daytime HD for 97 +/- 68 months were studied. No significant
      difference was found in every daytime and nighttime BP between the first (HD) and
      the second (non-HD) day. However, the ratio nighttime/daytime BP was
      significantly higher on the second day. Each BP diurnal variability pattern was
      classified as either Dipper (D: the ratio nighttime/daytime mean BP 0.8-0.9), non
      dipper (0.9 < ND < 1.0), or inverted dipper (ID > 1.0). More than 75% of the
      cases were classified as ND (26 cases) or ID (11 cases). The ultrafiltration rate
      in D was significantly less than that in ND and ID. The difference of plasma
      renin activity between pre- and post-HD (dRen) was significantly higher in ID
      than in D and ND. The amount of dialysis (Kt/V) was found to be significantly
      correlated with nighttime BP fall. Ultrafiltration, dRen and Kt/V were
      independent factors for the abnormal BP diurnal variability. In conclusion, the
      decreased nocturnal BP fall seen in non-diabetic HD patients is associated with
      increased extracellular fluid even in the patients without overt overhydration,
      whereas relatively insufficient amount of dialysis (low Kt/V) may be another
      possible cause. The increased dRen observed only in ID patients may reflect
      occult cardiovascular damage or functional disturbances in aortic and carotid
      baroreflexes caused by arterial structural changes.

PMID- 11325070
TI  - Role of endothelin-1/endothelin receptor system in endotoxic shock rats.
AB  - Endothelin (ET)-1, a potent vasoconstrictor peptide derived from the endothelium,
      is markedly increased in endotoxic shock, although the pathophysiological role of
      ET-1 under septic conditions remains obscure. To delineate the role of ET-1 and
      its receptor subtype in endotoxic shock, we here attempted to determine the
      changes of circulating levels of ET-1 and its biosynthetic intermediate big ET-1
      in endotoxic shock rats, to evaluate the gene expression of ET-1 as well as the
      ET-1 receptor subtypes (ETA and ETB) in the heart, lung and liver, and to study
      the effects of ET receptor antagonists on systemic arterial blood pressure, heart
      rate and survival rate. Administration of bacterial lipopolysaccharide (LPS)
      caused profound hypotension, increased heart rate and death, and these effects
      were blocked by a nonselective ETA/ETB receptor antagonist (TAK044), but not by
      an ETA selective antagonist (BQ123). Administration of exogenous ET-1 caused a
      profound pressor response in control rats, but not in the LPS-pretreated rats.
      Injection of LPS caused marked elevation of plasma levels of both ET-1 and big ET
      1, which were not affected by treatment with either ET receptor antagonist.
      Administration of LPS caused up-regulation of ET-1 and ETB receptor mRNA in the
      heart, whereas ETA receptor mRNA was markedly down-regulated in the heart, lung
      and liver. These data suggest differential gene regulation of ET-1 and its
      receptor subtypes in various organs from endotoxic shock rats, and that
      nonselective ETA/ETB receptor antagonist, but not ETA receptor antagonist,
      ameliorates endotoxin-induced hypotension and death.

PMID- 11325071
TI  - Mechanism of sodium load-induced hypertension in non-insulin dependent diabetes
      mellitus model rats: defective dopaminergic system to inhibit Na-K-ATPase
      activity in renal epithelial cells.
AB  - Obesity-related non-insulin dependent diabetes mellitus (NIDDM) is frequently
      accompanied by hypertension. The present study was designed to clarify this
      mechanism. We first determined the blood pressure in male Wistar fatty rats
      (WFR), one of the NIDDM model rats, and in Wistar lean rats (WLR) as the control,
      with a normal (0.7% NaCl) or high (7% NaCl) salt diet. We observed no difference
      in systolic and mean blood pressures between WFR and WLR. WFR, however, became
      extremely hypertensive as a result of ingesting the high salt diet. We next
      investigated the mechanism for sodium sensitivity in WFR. Although the urinary
      excretion of dopamine (DA), a potent natriuretic factor, which reflects the
      ability for renal DA production, was preserved in WFR, the sodium balance with
      the high salt diet was positive. Moreover, Na-K-ATPase activity in isolated
      proximal convoluted tubules (PCT) from WFR with a normal salt diet was
      significantly (p<0.05) higher than that from WLR. A high salt load produced a
      significant (p<0.05) decrease in Na-K-ATPase activity in WLR but not in WFR.
      Similarly, Na-K-ATPase activity in WLR with a normal salt diet was significantly
      (p<0.05) inhibited by DA (10(-5) M), but this was not true in WFR. Furthermore,
      urinary excretion of norepinephrine in WFR with a high salt diet was the highest
      among all the groups. These results indicate that WFR tend to develop salt
      sensitive hypertension that could be caused by the excessive sodium retention
      occurring as the results of a defective dopaminergic system in the kidney that
      fails to inhibit Na-K-ATPase activity. Augmentation of the renal sympathetic
      nervous system may play some role in this setting.

PMID- 11325072
TI  - Stimulatory effect of endothelin-1 on neurons in the nucleus tractus solitarii is
      mediated by non-N-methyl-D-aspartate receptors.
AB  - We previously demonstrated that endothlin-1 (ET-1) augments and ETA receptor
      antagonist attenuates excitatory neuronal response to glutamate (Glu) in
      brainstem slices from normotensive rats. The aim of this study was to determine
      which type of Glu receptor is responsible for the stimulatory effects of ET-1 on
      neurons of the nucleus tractus solitarii (NTS). Single unit discharges were
      recorded extracellularly from rat brainstem slice preparations. Seven NTS neurons
      that were excited by solitary tract (ST) stimulation responded to
      iontophoretically applied ET-1 with neuronal activity. An N-methyl-D-aspartate
      (NMDA) receptor antagonist, non-NMDA, 6-cyano-7-nitro-quinoxaline-2, 3-dione
      (CNQX), or DL-2-amino-5-phosphonovaleric acid (AP-5) was perfused over the slices
      with Kreb's-Ringer solution. The increase in neuronal activity evoked by
      iontophoretically applied ET-1 was nearly abolished by CNQX but not by AP-5. CNQX
      but not AP-5 decreased the basal spontaneous neuronal activity of NTS neurons.
      These results suggest that non-NMDA receptors play a role in mediating the
      stimulatory effect of ET-1 on neuronal activity in the NTS.

PMID- 11325073
TI  - Leisure-time physical activity and other factors in relation to blood pressure in
      Japanese-Americans in Hawaii, USA.
AB  - To examine physical activity at work and during leisure-time as well as other
      factors related to blood pressure (BP) in Japanese-Americans living in Hilo,
      Hawaii, USA, we performed a population-based cross-sectional study with a sample
      of 238 participants aged 42-64 years old. This survey was carried out between 19
      February and 1 March 2000 in Hilo. All participants were invited to Hilo Medical
      Center for a free physical examination and experimental tests including an
      examination of blood and urine samples. A self-administered health questionnaire
      was used that included items related to demographics, smoking, alcohol
      consumption, and habitual physical activity at work and during leisure-time. A
      summary score of physical activity (PA) was calculated. BP was measured using an
      automated BP measurement system (Khi machine, VINE Co., Ltd., Kyoto, Japan). The
      results showed the following. 1) Mean (SD) PA scores at work (WPA) and during
      leisure-time (LTPA) were 2.9 (0.5) and 2.5 (0.5) in men, and 3.0 (0.5) and 2.4
      (0.3) in women, respectively; 2) Pearson correlation analyses (adjustment for
      age) indicated that WPA and LTPA in men show significant negative associations
      with SBP and DBP (p<0.05 and p<0.01), while LTPA shows significant negative
      associations with SBP and DBP in women (p<0.05 and p<0.01). After further
      adjustment for education, occupation, smoking, and alcohol consumption status,
      LTPA continued to show significant and negative associations with both SBP and
      DBP in men (p<0.01) and with DBP alone in women (p <0.01). 3) Hypertensive
      subjects had significantly lower mean LTPA scores than normotensive men (2.39 vs.
      2.61, p<0.05) and women (2.32 vs. 2.45, p<0.05). 4) Body mass index and the ratio
      of sodium to potassium excretion showed significant and positive associations
      with SBP and DBP in multiple linear regression analyses. In conclusion, the
      results further emphasize that the health benefits of LTPA, control of body
      weight, and reduction in salt intake should continually receive strong attention
      in population-based high BP control.

PMID- 11325074
TI  - Comparison of the effects of an ACE inhibitor and alphabeta blocker on the
      progression of renal failure with left ventricular hypertrophy: preliminary
      report.
AB  - The aim of this study was to compare the effects of an angiotensin-converting
      enzyme (ACE) inhibitor and alphabeta blocker in combination with a calcium
      antagonist on the progression of renal function and left ventricular hypertrophy
      (LVH) in patients with chronic renal insufficiency and hypertension. The 65
      subjects in this study were recruited from a cohort of 316 patients. The main
      criteria for inclusion were echocardiographic diagnosis of LVH (posterior wall
      thickness >12 mm) and serum creatinine of more than 1.5 mg/dl. Antihypertensive
      treatments were switched to the combination of amlodipine at a dose of 5 mg and
      benazepril at a dose of 2.5 mg daily or the combination of amlodipine at a dose
      of 5 mg and arotinolol at a dose of 20 mg daily at random irrespective of whether
      or not patients had been previously treated. The follow-up period was 2 years.
      Systolic and diastolic blood pressure were significantly reduced from 150/90 +/-
      15/11 mmHg to 130/75 +/- 11/9 mmHg (ACE) and the levels of serum creatinine were
      increased significantly from 1.8 +/- 0.3 to 2.0 +/- 0.4 mg/dl (ACE). In the
      alphabeta-blocker group, these two values were similar and no significant changes
      were found. PWT was decreased from 14.2 +/- 0.6 to 12.9 +/- 0.3 cm in alphabeta
      blocker but was not significantly decreased in the ACE inhibitor group. In
      conclusion, combination therapy with a calcium antagonist and abeta blocker might
      be effective treatment for hypertensive patients with chronic renal insufficiency
      and left ventricular hypertrophy.

PMID- 11325075
TI  - A-6G variant of the angiotensinogen gene and essential hypertension in Han,
      Tibetan, and Yi populations.
AB  - To investigate the relationship between the A-6G variant in the promoter of the
      angiotensinogen gene and essential hypertension in Han, Tibetan, and Yi
      populations. All patients with essential hypertension were selected by WHO
      criteria. And the polymorphism of the A-6G variant was determined by PCR/RFLP.
      The data were analyzed by t test and chi2 test. There was no significant
      difference in the genotype or allele frequencies between normotensives and
      hypertensives in the Han, Tibetan, and Yi populations, respectively. However,
      when the subjects were divided into male and female subgroups, the genotype
      distributions among hypertensives and normotensives of the Tibetan female group
      were as follows: AA, 37% vs. 48%; AG, 52% vs. 48%; GG, 11% vs. 4%, respectively
      and the frequency of the G allele was significantly higher in hypertensives than
      in normotensives in the Tibetan female group (0.37 vs. 0.28, chi2=4.25, p<0.05).
      In addition, we observed that there was a significant difference between the Han
      and Tibetan normotensive groups in the distributions of the allele and genotype
      frequencies of the A-6G variant. The frequency of the G allele was 0.29 and 0.17
      in the Tibetan normotensive and Han groups, respectively (p<0.001). The G allele
      of the A-6G variant was associated with hypertension in the Tibetan females, but
      not in the Yi or Han females. And we confirmed that there was a significant
      difference in the prevalence of the allele frequencies of the A-6G variant
      between the Han and Tibetan normotensive groups.

PMID- 11325076
TI  - Effects of AT1 receptor antagonist on proteoglycan gene expression in
      hypertensive rats.
AB  - Proteoglycans are an important component of the extracellular matrix, and are
      thought to play multiple roles not only in kidney remodeling, but also in
      regulating glomerular permeability, and in modulating the activity of other
      cytokines and growth factors. The aim of this study was to examine the gene
      expressions of proteoglycan core proteins in hypertensive rat kidneys, and their
      modulation by AT1 receptor antagonist. SHRSP/Izm rats and normotensive control
      WKY/Izm rats on a normal salt diet were treated with or without the AT1 receptor
      antagonist candesartan cilexetil (1 mg/kg/day) from 10 weeks to 22 weeks. At the
      end of the treatment period, renal tissue was excised, and gene expressions of
      the proteoglycan core proteins versican, perlecan, decorin, and biglycan were
      examined by Northern blot analysis and RT-PCR. Treatment with candesartan
      cilexetil caused significant decreases in blood pressure and amelioration of
      proteinuria and renal histological scores in the SHRSP/Izm rats. Compared to
      WKY/Izm rats, expression of biglycan mRNA showed a small increase in SHRSP/Izm
      rats which did not attain statistical significance. On the other hand, treatment
      with candesartan caused significant reductions in biglycan and decorin mRNA in
      the SHRSP/Izm rats. In contrast, the level of versican mRNA appeared to be
      increased after candesartan treatment. These results suggest that treatment with
      AT1 receptor antagonist was associated with diverse changes in renal proteoglycan
      gene expression in SHRSP/Izm rats. These changes could contribute to the
      beneficial effects of AT1 receptor antagonist on tissue remodeling and inhibition
      of disease progression in hypertensive rat kidneys.

PMID- 11325077
TI  - The influence of chronic antihypertensive treatment on the central pressor
      response in SHR.
AB  - We examined the influence of chronic antihypertensive treatment on the central
      pressor response in SHR. Adult male SHR were divided into 5 groups, i.e., those
      receiving 1) enalapril (Enal: 25 mg/kg/day in drinking water, n=12); 2) losartan
      (Los: 40 mg/kg/day, n=11); 3) candesartan (Cand: 4 mg/kg/day, n=12); 4)
      hydralazine+hydrochlorothiazide (H&H: 50+7.5 mg/kg/day, n=9); 5) vehicle (
      CONTROL: n=9). At 4 weeks of treatment, hypertonic saline (0.25, 0.5 M) was
      intracerebroventricularly (i.c.v.) injected into conscious rats. Plasma
      catecholamines were measured before and after i.c.v. injection. On completion of
      the experiment, heart weight was measured, and angiotensin-converting enzyme
      (ACE) activity of the cerebrum was determined. All antihypertensive drugs
      elicited comparable reductions in systolic blood pressure, while heart rate was
      significantly higher in the H&H group than in the other groups during treatment.
      Pressor response to i.c.v. hypertonic saline (0.5 M) was significantly smaller in
      the Enal (12 +/- 3 mmHg) and Cand (11 +/- 2 mmHg) groups than in the Los (22 +/-
      2 mmHg), H&H (16 +/- 2 mmHg), and CONTROL (29 +/- 5 mmHg) groups. Plasma
      catecholamines did not differ among the groups. Heart weight was lowest in the
      Enal group, followed by the Los and Cand groups. ACE activity of the cerebrum was
      significantly decreased in the Enal group. The results suggest that chronic
      treatment with various antihypertensive drugs differentially alters the central
      pressor response in SHR, and enalapril and candesartan are effective in
      attenuating this response.

PMID- 11325078
TI  - Mechanism of the cardioprotective effect of inhibition of the renin-angiotensin
      system on ischemia/reperfusion-induced myocardial injury.
AB  - Inhibition of the renin-angiotensin system (RAS) has been shown to be beneficial
      in providing cardioprotective effects in humans, but the mechanism of these
      effects is not well understood. In this study, we examined the effects and
      mechanism of RAS inhibitors on ischemia/reperfusion (IR)-induced myocardial
      injury in rats. Rats were randomly divided into five groups and treated with
      vehicle (C), angiotensin converting enzyme inhibitor (ACE-I), angiotensin II type
      1 receptor antagonist (AT1-A), angiotensin II type 2 receptor antagonist (AT2-A)
      or ACE-I plus bradykinin B2 antagonist. Ten minutes after administration, the
      left main coronary artery was ligated for 45 min, and then reperfused for 120
      min. IR-induced cardiomyocyte apoptosis was assessed by terminal
      deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay
      and confirmed by typical DNA laddering. Mitogen-activated protein kinase,
      extracellular signal-regulated protein kinase (ERK) and c-Jun NH2-terminal
      protein kinase (JNK) activity in the ischemic zone were measured by an in vitro
      kinase assay. The duration of ventricular tachycardia (VT) during ischemia was
      reduced by AT2-A and ACE-I, and increased by AT1-A and ACE-I+icatibant. ACE-I and
      AT2-A reduced apoptosis (by 54% and 53%) and infarct size (by 42% and 41%), while
      AT1-A increased apoptosis (by 86%) and infarct size (by 45%). These changes were
      negatively correlated with the change in ERK activity. The effects of ACE-I on
      apoptosis and infarct size were abolished by the coadministration of icatibant.
      Apoptosis was correlated with the occurrence of VT (r=0.837, p<0.001). These
      results suggest that both the accumulation of bradykinin and inhibition of AT2
      receptor are cardioprotective against IR injury through the activation of ERK,
      but not JNK.

PMID- 11325079
TI  - Determination of optimal blood pressure for patients with IgA nephropathy based
      on renal histology.
AB  - To evaluate the optimal BP control for patients with IgA nephropathy (IgAN) based
      on the histologic severity of the nephropathy and the degree of renal
      dysfunction. We analyzed 332 consecutive renal biopsy specimens and clinical data
      from patients with IgAN. Patients were divided into three groups based on their
      BP at the time of biopsy: an optimal BP (SBP<120 mmHg and DBP<80 mmHg), a
      hypertensive BP (SBP > or = 140 mmHg and/or DBP > or = 90 mmHg), and an
      intermediate BP group. Each biopsy specimen was evaluated for mesangial
      proliferation, degree of sclerosis and/or hyalinosis of the arterioles and the
      interlobular artery using a semiquantitative method. Creatinine clearance and the
      percentage of sclerosed glomeruli were also determined. Both the degree of renal
      dysfunction and the histologic changes correlated significantly with BP, even in
      patients with a BP <140/90 mmHg. The patients with an optimal BP at the time of
      biopsy had significantly less histologic damage with respect to mesangial
      proliferation and vessel changes than those with an intermediate or hypertensive
      BP. In the patients with a hypertensive BP, the percentage of sclerotic glomeruli
      was significantly higher and the creatinine clearance was significantly lower.
      The optimal BP proposed by the WHO in 1999 prevents histologic evidence of renal
      damage for patients with IgAN.

PMID- 11325080
TI  - Family history of hypertension and blood pressure in a screened cohort.
AB  - We sought to determine whether a family history of hypertension is quantitatively
      associated with the prevalence of hypertension and blood pressure in a screened
      cohort. Clinical data and family (parents and siblings) histories regarding
      hypertension were collected from 9,914 individuals (probands) who were
      interviewed and examined during a one-day clinic by the Okinawa General Health
      Maintenance Association in 1997. We used logistic analysis to calculate odds
      ratios with adjustments for age, sex, body mass index, total cholesterol,
      presence of diabetes mellitus, alcohol use, cigarette smoking, and status of
      physical exercise. The age- and sex-adjusted hypertension prevalences in probands
      were 29.0% for those with 1 family member with a history of hypertension
      (n=2,112), 37.6% for those with 2 hypertensive family members (n=374), and 47.3%
      for those with 3 or more hypertensive family members (n=68). In contrast, only
      16.4% of probands who reported no family history of hypertension (n=7,360) were
      hypertensive themselves. The trend of the prevalence according to the number of
      family members with a history of hypertension was significantly positive
      (p=0.003). The adjusted odds ratios (95% confidence interval) of hypertension
      were 2.74 (2.43-3.10) for 1 member, 4.62 (3.62-5.90) for 2 members, and 6.04
      (3.51-10.4) for 3 or more members with a history of hypertension. In patients
      without antihypertensive medication (n=9,009), systolic/diastolic blood pressure
      (mean +/- SD) was 121 +/- 17/75 +/- 11 for 1 member, 124 +/- 18/77 +/- 12 for 2
      members, and 127 +/- 17/78 +/- 11 for 3 or more members with a history of
      hypertension. In contrast, the mean systolic/diastolic blood pressure of probands
      who reported no family history of hypertension (n=7,360) was 119 +/- 15/74 +/- 10
      mmHg, which was significantly (p<0.05) lower than that of any of the groups with
      hypertensive family members. In conclusion, an increase in the number of family
      members with hypertension was associated with an increasing prevalence of
      hypertension and blood pressure in the probands, independent of conventional risk
      factors for hypertension. Family members of hypertensive subjects may need to be
      treated in primary prevention efforts related to hypertension.

PMID- 11325081
TI  - High serum level of procollagen type III amino-terminal peptide contributes to
      the efficacy of spironolactone and angiotensin-converting enzyme inhibitor
      therapy on left ventricular hypertrophy in essential hypertensive patients.
AB  - We recently demonstrated that spironolactone may have beneficial effects on left
      ventricular hypertrophy in selected patients with essential hypertension
      undergoing treatment with an angiotensin-converting enzyme (ACE) inhibitor. To
      clarify the possible mechanisms by which spironolactone improves cardiac
      hypertrophy, we investigated the change in serum procollagen type III amino
      terminal peptide (PIIINP) in 11 patients with essential hypertension treated with
      spironolactone and an ACE inhibitor for 24 weeks. Both blood pressure and serum
      PIIINP levels were significantly decreased by treatment. There was a statistical
      significant correlation between the changes in LVMI and those in PIIINP. The
      reduction in PIIINP was significant in patients whose initial serum PIIINP levels
      were above the normal range. Before treatment, there were no statistically
      significant correlations between serum PIIINP levels and either LVMI, blood
      pressure, or plasma aldosterone concentration. Essential hypertensive patients
      matched in terms of duration of therapy, blood pressure and LVMI and treated with
      an ACE inhibitor alone showed no change in serum PIIINP levels. In conclusion,
      the results of the present study demonstrate that patients with essential
      hypertension and high serum levels of PIIINP are particularly responsive to MR
      blockade in terms of left ventricular hypertrophy. Moreover, these results
      suggest that spironolactone limits cardiac collagen turnover in such patients.
      Larger studies may provide definitive evidence for the involvement of aldosterone
      in left ventricular hypertrophy in patients with abnormally high PIIINP levels.

PMID- 11325082
TI  - Laparoscopic orthotopic ileal neobladder.
AB  - BACKGROUND AND PURPOSE: Orthotopic ileal neobladder is currently the preferred
      continent urinary diversion in suitable patients undergoing radical cystectomy
      for muscle-invasive bladder cancer. To our knowledge, presented herein is the
      initial report of laparoscopic orthotopic ileal neobladder following cystectomy
      that was performed completely intracorporeally in a porcine model. MATERIALS AND
      METHODS: The laparoscopic technique was developed in seven pigs. Subsequently, a
      long-term survival study was performed in 12 consecutive animals. Laparoscopic
      cystectomy was performed, preserving the urethral sphincter. An ileal segment of
      35 cm (first three animals), 45 cm (next four), or 55 cm (final five animals)
      with adequate mesentery was isolated; and ileal continuity was restored
      intracorporeally by a stapled anastomosis. Ileal detubularization for
      construction of an ileal neobladder, urethroileal anastomosis, and bilateral
      stented ileoureteral anastomoses to a tubular Studer limb extension were all
      created completely intracorporeally using only laparoscopic free-hand suturing
      and knot-tying. Biochemical data (preoperative and serial postoperative
      hemoglobin, renal panel, blood gases), radiologic studies (intravenous urogram,
      retrograde pouchgram), functional measures (neobladder urodynamics, Whitaker
      pressure-flow study of both ureters), and microscopic evaluation of the
      neobladder and ureteroileal and urethroileal anastomotic sites were obtained to
      evaluate the long-term functional and anatomic outcome. RESULTS: Completely
      intracorporeal laparoscopic construction of an ileal orthotopic neobladder was
      successful in all 12 animals without intraoperative or early postoperative
      complications or open conversion. The mean operating time was 5.4 hours (range
      4.5-6.5 hours), and the blood loss was minimal. All study pigs survived their
      predetermined follow-up period, ranging from 1 to 3 months. Late complications
      occurred in three animals: one port-site abscess and two cases of E. coli
      pyelonephritis and azotemia, leading to one death at 2 months. The mean serum
      creatinine concentrations were 1.33 mg/dL, 1.61 mg/dL, and 1.55 mg/dL at 1, 2,
      and 3 months, respectively. The mean neobladder capacity was 420 mL (range 250
      700 mL) with pressures < or = 20 cm H2O (range 17-20 cm H2O). Pre-euthanasia
      Whitaker testing confirmed excellent drainage in all 24 ureters. No ileoureteral
      or ileourethral anastomotic strictures or leaks were noted on intravenous
      urography, retrograde pouchgram, or postmortem physical calibration of the
      anastomotic sites. Histologic examination confirmed excellent healing without
      obvious fibrosis. CONCLUSION: Laparoscopic construction of an orthotopic
      neobladder is feasible. The anatomic and functional outcome is excellent and
      comparable to that of open surgery. Clinical application is imminent.

PMID- 11325083
TI  - Laparoscopic renal autotransplantation.
AB  - BACKGROUND AND PURPOSE: Renal autotransplantation is an extensive open surgical
      operation consisting of two distinct procedures, live-donor nephrectomy and
      autotransplantation, and requiring two large skin incisions. Herein, we analyze
      the feasibility of performing the entire procedure laparoscopically. MATERIALS
      AND METHODS: Renal autotransplantation was performed entirely laparoscopically in
      six female farm pigs. Following a left donor nephrectomy, intracorporeal renal
      hypothermia was achieved by intra-arterial perfusion of ice-cold solution through
      a 4F balloon catheter. During autotransplantation, the renal vessels were
      anastomosed intracorporeally to the previously prepared ipsilateral common iliac
      vessels in an end-to-side fashion. Laparoscopic freehand suturing (5-0 Prolene)
      and knot-tying techniques were employed exclusively. A staged contralateral
      native nephrectomy was performed in five animals. Postoperative follow-up
      included serial creatinine measurements, intravenous urography, aortography, and
      renal histologic examination. RESULTS: The mean operating time was 6.2 hours
      (range 5.3-7.9 hours), the venous anastomosis time was 33 minutes (range 22-46
      minutes), the arterial anastomosis time was 31 minutes (range 27-35 minutes), and
      the total iliac clamping time was 77 minutes (range 62-88 minutes). The total
      renal ischemia time was 68.7 minutes: warm ischemia 5.1 minutes, cold ischemia 33
      minutes and rewarming 31 minutes. Serum creatinine concentrations remained
      stable: baseline 1.3 mg/dL, after autotransplantation 1.1 mg/dL, and after
      contralateral nephrectomy 1.6 mg/dL. Intravenous urography and aortography prior
      to euthanasia (N = 5) demonstrated prompt contrast uptake and excretion by the
      autotransplanted kidneys and patent arterial anastomoses, respectively.
      Histopathologic examination of the autograft demonstrated normal renal
      architecture. CONCLUSIONS: Renal autotransplantation can be performed utilizing
      laparoscopic techniques exclusively. This study may form the basis for
      performance of complex urologic vascular procedures laparoscopically.

PMID- 11325084
TI  - Indwelling ureteral stents: evaluation of quality of life to aid outcome
      analysis.
AB  - BACKGROUND: Ureteral stents cause various side effects. We have evaluated health
      related quality of life (HRQoL) in patients with stents using validated
      questionnaires and developed a new stent symptom (intervention)-specific
      questionnaire (SSQ). PATIENTS AND METHODS: Along with structured literature
      review and in-depth interviews, prospective sub-studies were carried out using
      generic (SF-36 [N = 30], EuroQol [N = 40], and Functional Status Questionnaire
      FSQ [N = 20]) and symptom-specific (IPSS [N = 30] and International Continence
      Society ICS [N = 30]) questionnaires both with a stent in situ and after removal.
      The results of these studies formed the foundation for a new SSQ that was pilot
      tested (N = 10) and field tested (N = 20) in order to develop a final draft of
      the questionnaire that is formally validated. RESULTS: The qualitative research
      identified a range of problems. Urinary symptoms, pain, work performance, and
      general health were the most important. Most patients (80%) experienced
      bothersome urinary symptoms and stent-related pain. Storage symptoms and
      incontinence were significant urinary symptoms affecting quality of life. As many
      as 40% of patients experienced sexual dysfunction. The stent had a significant
      impact on patients' general health. None of the existing measures evaluated the
      complete impact. The SSQ includes five sections covering urinary symptoms, pain,
      sexual matters, general health, and work performance. The preliminary results
      showed it to be valid, reliable (alpha > 0.7) and responsive to the change in
      scores (p < 0.05) after stent removal. CONCLUSIONS: Indwelling ureteral stents
      are associated with significant morbidity, resulting in a reduced HRQoL in 80% of
      patients. The SSQ is a reliable intervention-specific instrument that would be
      useful as an outcome measure to evaluate the impact of stents.

PMID- 11325085
TI  - Escherichia coli-human uroepithelial cell interaction products enhance fibroblast
      migration and matrix accumulation.
AB  - BACKGROUND AND PURPOSE: Urinary tract infection has been associated with renal
      interstitial scarring and ureteral wall fibrosis. The mechanism of progression of
      scarring despite attenuation of the primary insult is not clear. We examined the
      role of the products of the interaction between Escherichia coli and human
      uroepithelial cells (HUC-EC-S) on the migration of fibroblasts, as well as their
      matrix synthesis. MATERIALS AND METHODS: We evaluated the effect of HUC-EC-S
      (concentration of 10%, 15%, and 25%) on the migration of fibroblasts across a
      filter in a modified Boyden chamber. To determine the role of transforming growth
      factor-beta and MCP-1, we studied the effect of anti-TGF-beta and anti-MCP-1
      antibodies on interaction product-induced fibroblast migration. The effect of HUC
      EC-S on fibronectin and collagen I accumulation was studied by the Western
      blotting. RESULTS: Bacterial-HUC interaction products enhanced (P < 0.001)
      migration of fibroblasts compared with uroepithelial interaction product (HUC-S).
      Anti-TGF-beta and anti-MCP-1 antibodies partly inhibited (P < 0.001) the HUC-EC-S
      induced fibroblast migration. Also, HUC-EC-S-treated fibroblasts showed enhanced
      accumulation of fibronectin and collagen 1. CONCLUSION: Escherichia coli-induced
      activation of HUC not only promotes migration of fibroblasts but also triggers
      matrix remodeling.

PMID- 11325086
TI  - Hand-assisted laparoscopic partial nephrectomy.
AB  - BACKGROUND AND PURPOSE: The indications for partial nephrectomy are expanding as
      newer and more complete data come forth. A partial nephrectomy has traditionally
      required a generous flank incision. We report our experience using hand-assisted
      laparoscopy (HAL) as a less-invasive approach to partial nephrectomies. PATIENTS
      AND METHODS: Between October 1999 and May 2000, we performed 11 HAL partial
      nephrectomies. The average age of the patients was 55.7 years, the average body
      mass index was 25.6, and the average ASA class was 2.2. The indications for
      partial nephrectomy were enhancing solid renal lesions (N = 9) and nonfunctioning
      renal moiety in a duplicated system (N = 2). In the majority of cases, access to
      the renal pedicle was obtained prior to the partial nephrectomy. However, in no
      case did the renal artery or vein require occlusion. Several excisional
      techniques were employed, but all relied heavily on the Harmonic Scalpel in
      conjunction with the argon beam coagulator. Different hemostatic agents were
      applied to the renal defect, including Surgicel, Avitene, and fibrin-soaked
      Gelfoam activated by thrombin. In several instances, pledget reinforced sutures
      were placed in the renal capsule to aid with hemostasis. RESULTS: The average
      operative time was 273 minutes, the estimated blood loss 319 mL, and the change
      in hematocrit 7.3 points. No patient required a transfusion, and there was one
      conversion to open. Postoperatively patients, required an average of 35.6 mg of
      morphine sulfate equivalent and 8.2 narcotic tablets, resumed oral intake in 1.7
      days, and were discharged home in 3.3 days. There were no major complications and
      only two minor complications. Postoperatively, five lesions were found to be
      benign, four lesions were confirmed to be malignant, and two lesions were
      consistent with a nonfunctioning duplicated renal moiety. Specimen size averaged
      180 cc, and the tumor diameter averaged 1.9 cm. There were no positive surgical
      margins. CONCLUSIONS: Hand-assisted laparoscopic partial nephrectomy is feasible
      and reproducible. The surgeon's hand in the operative field facilitates
      dissection, vascular control, hemostasis, and suturing. Further long-term and
      prospective studies are underway.

PMID- 11325087
TI  - Intact specimen extraction during renal laparoscopy: muscle-splitting versus
      muscle-cutting incision.
AB  - PURPOSE: To determine whether a muscle-splitting extraction incision decreases
      patient morbidity after renal laparoscopic surgery. PATIENTS AND METHODS: Twenty
      one patients undergoing laparoscopic simple nephrectomy, radical nephrectomy, or
      nephroureterectomy had intact specimen extraction through a muscle-splitting
      incision. The operative and recovery data of these patients were retrospectively
      compared with those of a matched cohort of 21 patients who underwent specimen
      extraction through a muscle-cutting incision. With the exception of a greater
      percentage of male patients in the muscle-cutting group (86% v 52%), there were
      no statistically significant differences between the two groups. RESULTS: In the
      muscle-splitting and muscle-cutting groups, there was no significant differences
      in regard to analgesic use (9.0 +/- 6.6 mg of morphine sulfate equivalent v 7.9
      +/- 4.9; P < 0.51), hospital stay (31.2 hours v 30 hours; P < 0.79), recovery
      (6.7 +/- 4.7 days v 5.7 +/- 4.7 days; P < 0.38), or convalescence (4.2 +/- 2.2
      weeks v 4.1 +/- 2.0 weeks; P < 0.90). CONCLUSION: A muscle-splitting incision for
      intact renal specimen extraction does not necessarily decrease postoperative
      morbidity compared with a muscle-cutting extraction.

PMID- 11325088
TI  - Prospective double-blind study of effect of ketorolac administration after
      laparoscopic urologic surgery.
AB  - BACKGROUND AND PURPOSE: To decrease postoperative dependence on narcotics for
      analgesia, we have evaluated ketorolac as an adjunct to perioperative pain
      control in patients undergoing laparoscopic urologic surgery. PATIENTS AND
      METHODS: Sixty-five patients (34 male, 31 female) were randomized to receive
      either ketorolac tromethamine (15-30 mg IV q 6 h) or placebo prior to
      laparoscopic surgery. Patient-controlled analgesia in the form of morphine
      sulfate was provided. Operative factors such as the type of surgery, operative
      time, and estimated blood loss were recorded. Postoperative factors such as
      analog pain score (range 0-10), narcotic usage, and length of stay were
      evaluated. RESULTS: Fifty-five patients completed the study. The average pain
      score was 2.2 and 4.5 for the ketorolac and placebo groups, respectively (P <
      0.005). The mean amounts of total morphine used were 39.2 mg (ketorolac) and 62.5
      mg (placebo) (P = 0.077). The length of stay was not significantly different in
      the ketorolac (2.5 days) and placebo (2.6 days) groups (P = 0.74). Operative
      times (P = 0.21) and estimated blood loss (P = 0.60) were not significantly
      different in the two groups. Ketorolac did not adversely affect renal function;
      serum creatinine changes were not significantly different from those in the
      patients receiving placebo (P = 0.50). Laparoscopic pyeloplasty necessitated more
      narcotic analgesia than did other laparoscopic procedures (P = 0.05). CONCLUSION:
      Ketorolac decreases the subjective perception of pain after laparoscopic urologic
      surgery. It is suggested that ketorolac administration decreases the amount of
      narcotic usage as well. Time to resumption of oral intake and length of hospital
      stay were not influenced by use of ketorolac.

PMID- 11325089
TI  - Laparoscopic repair of incisional and parastomal hernias after major
      genitourinary or abdominal surgery.
AB  - BACKGROUND AND PURPOSE: Abdominal wall or parastomal hernias following major
      genitourinary or abdominal surgery are a significant surgical problem. Open
      surgical repair is difficult because of adhesion formation and poor definition of
      the hernia fascial edges. Laparoscopic intervention has allowed effective
      correction of these abdominal wall hernias. PATIENTS AND METHODS: From November
      1997 to June 2000, 14 male and 3 female patients underwent laparoscopic abdominal
      wall herniorrhaphy at our institution. Of these, 13 patients received incisional
      and 4 parastomal hernia repair. All hernia defects were repaired using a measured
      piece of Gore-Tex DualMesh. A retrospective review of each patient's history and
      operative characteristics was undertaken. RESULTS: All repairs were successful.
      No patient required conversion to an open procedure, and there were no
      intraoperative complications. The average operative time was 4 (range 2.5-6.5)
      and 4.3 (range 3.75-5.5) hours in the incisional and parastomal group,
      respectively. The average hospital stay was 4.9 days (range 2-12) for the
      incisional group and 3.8 (range 3-4) days for the parastomal group. To date, two
      patients experienced a recurrence of incisional hernias, at 5 and 8 months
      postoperatively. No recurrences have developed in the parastomal hernia repairs
      at 2 to 33 months. CONCLUSION: Laparoscopic repair of abdominal wall incisional
      or parastomal hernias provides an excellent anatomic correction of such defects.
      Adhesions are lysed under magnified laparoscopic vision, and the true limits of
      the fascial defects are clearly identified. The DualMesh is easy to work with and
      has yielded excellent results. A comparison with open repair with respect to
      perioperative factors and long-term success is currently under way.

PMID- 11325090
TI  - Role of stone analysis in metabolic evaluation and medical treatment of
      nephrolithiasis.
AB  - BACKGROUND AND PURPOSE: Comprehensive metabolic evaluation has become an
      important aspect of the management of recurrent nephrolithiasis, yet the role of
      stone analysis is often neglected or perhaps underestimated. The purpose of this
      study was to determine the role of stone analysis in medical decision making in
      patients with recurrent nephrolithiasis. MATERIALS AND METHODS: We evaluated 100
      consecutive stone-forming patients who had undergone compositional stone analysis
      as well as comprehensive metabolic evaluation at our institution. An analysis of
      stone composition in relation to metabolic disturbances was performed. Patients
      were stratified into two groups: calcium and non-calcium stone formers. RESULTS:
      Patients having non-calcium stones were found to have a metabolic analysis
      reflecting specific metabolic disorders. Alternatively, patients with calcium
      stones were heterogeneous with regard to metabolic disorders, but there was a
      significant likelihood of renal tubular acidosis in those patients with calcium
      phosphate calculi. On the basis of these results, a simplified metabolic
      evaluation and nonselective medical therapy based on stone composition was
      formulated to facilitate assessment, management, and monitoring of stone disease.
      CONCLUSIONS: Compositional stone analysis should be an integral part of the
      metabolic evaluation of patients with nephrolithiasis. Moreover, stone analysis
      alone may provide guidance for therapeutic treatment and obviate a formal
      metabolic evaluation.

PMID- 11325091
TI  - Comparison and analysis of laparoscopic intracorporeal suturing devices:
      preliminary results.
AB  - BACKGROUND AND PURPOSE: One of the most challenging aspects of laparoscopic
      surgery is intracorporeal suturing and knot tying. A loss of depth perception and
      tactile sense and visual obstruction make placing accurate and well-tied knots a
      difficult and time-consuming task. Two devices conceived to ease the task of
      suturing and knotting while presumably speeding performance are the Suture Assist
      (SA; Ethicon Endo-Surgery) and EndoStitch (ES; US Surgical/Tyco). We set out to
      objectively assess suture placement accuracy and knot speed and strength of these
      two suturing devices and conventional laparoscopic suturing (CS). MATERIALS AND
      METHODS: To date, six surgeons with laparoscopic experience were trained on the
      three suturing techniques. A pelvic trainer was set up with a freshly marked and
      incised swine renal pelvis and ureter. Each surgeon placed four sutures of 2-0
      polyester suture with each technique (repeated on three separate occasions) with
      five half-hitches for a total of 216 knots. Time, strength, and accuracy were
      measured for each suture/knot placement. The knot distance was then measured from
      the marked target using calipers and carefully dissected from the tissue. Each
      knot was individually tested on a Monsanto Model 10 tensiometer, whereby
      slippage, strength, and breakage points were determined. RESULTS: The mean times
      (min:sec) and accuracy (millimeters) were as following: CS 5:08 and 0.457, ES
      2:45 and 0.660, and SA 2:40 and 0.508. The difference in time was found to be
      statistically significant (P < 0.001), while the difference in accuracy was not.
      Only 182 of 216 knots were able to be included for analysis because of either a
      small knot lumen or device failure. Device failures necessitating intervention
      were encountered only with the SA, which had a misfire rate of 9.7% (7 of 72).
      The mean knot strength was measured at 41.1 N for CS, 57.3 N for SA, and 28.0 for
      ES. Knot break percentage (breakage) was calculated as 50.8% for CS, 20.7% for
      ES, and 95% for SA. CONCLUSION: Preliminary results show that each of the
      laparoscopic suturing devices has distinct advantages over conventional
      intracorporeal suturing and tying. Decreased times and comparable, if not
      greater, knot strengths may translate into improved laparoscopic suturing/tying
      performance for laparoscopic intracorporeal suturing devices.

PMID- 11325092
TI  - Measurement and prediction of thermal behavior and acute assessment of injury in
      a pig model of renal cryosurgery.
AB  - PURPOSE: To analyze in vivo end temperatures and histologic injury in a
      standardized cryo-iceball using a porcine kidney model in order to establish the
      threshold temperature for tissue ablation. To evaluate the ability to predict end
      temperatures using a thermal finite element model. MATERIALS AND METHODS: A
      single freeze/thaw cryolesion was created in five pig kidneys and the temperature
      history recorded. End temperature was calculated using a thermal finite element
      model. The threshold temperature for tissue injury was established by directly
      correlating end temperature and histologic injury. RESULTS: Reproducible geometry
      and temperature profiles of the cryo-iceball were found. End temperature could be
      accurately predicted through thermal modeling, and correlation with histologic
      injury revealed a threshold temperature of -16.1 degrees C for complete tissue
      ablation. CONCLUSION: Thermal modeling may accurately predict end temperature
      within a cryo-iceball. Provided threshold temperatures for tissue destruction are
      known, modeling may become a powerful tool in cryosurgery, improving the
      assessment of damage in normal and malignant tissue.

PMID- 11325093
TI  - Laparoscopic transverse hemicystectomy with ileocystoplasty in a porcine model.
AB  - BACKGROUND AND PURPOSE: The ideal replacement for bladder tissue is yet to be
      described, although multiple alternatives have been studied. Currently,
      enterocystoplasty, despite its limitations, is considered the gold standard for
      bladder augmentation. This study evaluated the feasibility, safety, and morbidity
      of laparoscopic ileocystoplasty in a large-animal model. MATERIALS AND METHODS:
      In eight minipigs, laparoscopy was performed using four ports. A segment of ileum
      was delivered through a 3-cm umbilical incision and detubularized and refashioned
      using standard open surgical technique. Laparoscopic hemicystectomy was then
      performed, followed by laparoscopic suturing of the ileal patch to the bladder.
      The bladder was drained with a Foley catheter, but no pelvic drain was placed.
      All animals were followed for for a minimum of 3 months. Preoperative and
      postoperative evaluation included measurement of bladder capacity, ultrasound
      imaging of the kidneys, blood counts, and serum electrolyte and creatinine
      measurements. Two of the animals were sacrificed at 3 months and one at 6 months,
      and the bladders were harvested. RESULTS: Eight animals underwent ileocystoplasty
      without intraoperative or postoperative complications. The average operating and
      anastomosis time was 250 minutes and 96 minutes, respectively. All animals had
      normal preoperative blood values that remained normal during follow-up. Bladder
      capacity decreased initially to 71% of the baseline volume and then increased to
      83% and 117% at 3 and 6 months. One of three animals sacrificed was noted to have
      a right midureteral stricture. CONCLUSIONS: We developed a reliable laparoscopic
      technique for ileocystoplasty that may extend the advantages of laparoscopy,
      including better cosmesis and reduced risk of postoperative adhesions, to bladder
      augmentation.

PMID- 11325094
TI  - Effects of fibrin glue on injured rabbit ureter.
AB  - BACKGROUND AND OBJECTIVE: Fibrin glue is used as a hemostatic agent, has
      potential as a tissue adhesive, and may promote tissue healing. The histologic
      effects of fibrin glue on the ureter have not yet been fully investigated. We
      studied the effect of fibrin glue on the thickness of various layers of injured
      and uninjured ureters and its effect on vessel density in the rabbit model.
      MATERIALS AND METHODS: Rabbits were divided into two groups. The ureters were
      exposed using a midline abdominal incision. In the study group, one of the
      ureters was crushed, and fibrin glue was instilled around both ureters. In the
      control group, one of the ureters was crushed, but no fibrin glue was instilled.
      The animals were sacrificed at 6 weeks and the ureters examined histologically.
      Using NIH Image Analysis solftware, the thickness of the urothelium, muscular,
      and adventitial layers and the cross-sectional area of the ureters were measured.
      The vessel density of the ureters was also assessed. RESULTS: Whereas the
      thickness of the epithelium was increased in the crushed ureters treated with
      fibrin glue (20.7 microm v 15.3 microm), the thickness was reduced in the
      uncrushed ureters treated with fibrin glue compared with controls (16.3 microm v
      19.8 microm). There was no statistically significant difference in the thickness
      of the muscular or adventitial layers in the study and control groups. There was
      a reduction in the cross-sectional area of the uncrushed ureters treated with
      fibrin glue compared with controls (7,095 microm2 v 9,409 microm2). In addition,
      the vessel density in the crushed ureters was reduced in ureters treated with
      fibrin glue compared with controls (0.00067/microm2 v 0.00108/micro2). In the
      uncrushed ureters, the difference was not statistically significant. CONCLUSIONS:
      Fibrin glue has potential as an adhesive agent in the ureter and may promote
      healing. It may affect epithelial layer thickness and vessel density of the
      ureter, but these effects were variable. Fibrin glue does not appear to have
      significant effects on the ureteral muscular and adventitial layers or on the
      overall cross-sectional area of all three layers. These results indicate that
      fibrin glue does not appear to have a detrimental effect on the ureter.

PMID- 11325095
TI  - Ischemia-reperfusion injury after relief of ureteral obstruction: an animal
      study.
AB  - BACKGROUND AND PURPOSE: The complex series of pathophysiologic alterations
      associated with obstruction nephropathy includes renal ischemia. Free-radical
      production follows relief of obstruction. We sought to determine whether free
      radicals caused additional reduction in blood flow after relief of obstruction.
      MATERIALS AND METHODS: In White-Landrace pigs, the left ureter was divided 6 cm
      distal to the ureteropelvic junction, and a nephrostomy tube was passed into the
      renal pelvis and exteriorized. A catheter was placed in the renal vein and
      exteriorized. Mean renal blood flow was measured before manipulation and during
      and after 6 hours of obstruction in animals receiving (N = 7) or not receiving (N
      = 7) allopurinol. The control groups were not subjected to ureteral obstruction
      and received (N = 7) or did not receive (N = 7) allopurinol. Free radicals in
      venous blood were measured by the Fox-1 assay for lipid peroxidation. RESULTS:
      After obstruction, renal blood flow declined significantly by the sixth hour (
      28.73% +/- 1.81). The increase after relief of obstruction was only temporary,
      and by the third hour, the blood flow was again reduced (-20.14% +/- 2.67). Free
      radical production was significantly increased, with a peak of +24.63% being
      found 60 minutes after relief of obstruction. Allopurinol prevented free radical
      production after relief of obstruction and was associated with a return of blood
      flow to baseline values. CONCLUSION: Free radicals contribute to renal blood flow
      reduction after relief of ureteral obstruction. Functional impairment may be
      preventable by free radical blockade, but further studies are required to confirm
      this hypothesis.

PMID- 11325096
TI  - Ureteral ischemia model: an explanation of ureteral dysfunction after chronic
      obstruction.
AB  - BACKGROUND AND PURPOSE: Many models of smooth muscle ischemia have been developed
      to explain organ insufficiency or failure. Ureteral decompensation may also be
      described in these terms. We anticipate that ureteral ischemia will result from
      overdistention brought about by obstruction. A preliminary model of an ischemic
      ureter is described herein. MATERIALS AND METHODS: Six female New Zealand rabbits
      were used for this study. All had their left ureters surgically ligated at the
      level of the urinary bladder. The right ureters served as controls. In the acute
      phase group, the ureters were reexplored 2 weeks after creation of obstruction.
      The other three rabbits were explored 3 weeks later. A laser Doppler needle was
      used to measure tissue perfusion with bilateral measurements of the renal artery
      and vein; renal parenchyma; renal pelvis; ureteropelvic junction; upper, mid, and
      lower ureter; and the lateral wall of the bladder. Baseline and postobstructive
      measurements of tissue perfusion were collected. RESULTS: In both the acute and
      chronic obstruction groups, there was a demonstrable drop-off in perfusion of the
      ureteral wall. CONCLUSION: The increased wall tension in the obstructed ureter
      results in a significant decrease in smooth muscle perfusion. This ischemia may
      result in the same functional and histologic changes that occur in other smooth
      muscle organs deprived of normal blood flow. Ultimately, poor outcomes of some
      restorative/reconstructive operations on the ureter may be explainable in terms
      of smooth muscle ischemia.

PMID- 11325097
TI  - Laparoscopic ureteral reconstruction with small intestinal submucosa.
AB  - PURPOSE: To evaluate the feasibility of laparoscopic ureteral reconstruction with
      small intestinal submucosa (SIS) in the pig ureter. MATERIALS AND METHODS: Eight
      female pigs weighing between 25 and 30 kg were enrolled. After anesthesia was
      administered, a double-pigtail stent was inserted, the animals were moved to a
      lateral decubitus position, pneumoperitoneum was established, and three 10-mm
      ports were positioned. The ureter was opened longitudinally for 7 cm, and two
      thirds of the periphery of the upper third of the left ureter was excised. The
      SIS was anastomosed to the upper and distal ureteral segments with chromic 4-0
      sutures. The double-pigtail stent was removed 6 weeks after the initial
      procedure, and retrograde pyelography was performed a week later to confirm the
      viability of the pelvicaliceal system. RESULTS: The average duration of the
      procedures was 210 minutes (range 125-250 minutes). All animals survived the
      entire follow-up period of 7 weeks. Retrograde pyelography revealed a patent
      ureteral lumen, and no obstructive phenomena were observed. Histologically, the
      SIS-regenerated ureteral segments were remarkably similar to normal porcine
      ureters and were indistinguishable from neighboring tissue. CONCLUSION:
      Laparoscopic ureteral reconstruction with SIS proved to be effective and
      technically feasible. The SIS seems to be an effective biodegradable scaffold,
      facilitating regeneration of host tissue.

PMID- 11325098
TI  - Stray radiofrequency current as a cause of urethral strictures after
      transurethral resection of the prostate.
AB  - PURPOSE: This study was designed to define the pattern and significance of stray
      currents induced by two electrosurgical generators (ESGs) in relation to urethral
      strictures forming after transurethral resection of the prostate (TURP).
      MATERIALS AND METHODS: A 24F resectoscope irrigated with glycine was activated at
      various power outputs in different modes, with intact loops and loops with faulty
      insulation, simulating TURP. The Valleylab and ERBE ESGs were compared for
      inducing capacitance. An ESG analyzer simulated tissue impedance and recorded the
      stray currents induced along the resectoscope sheath. A fresh pig liver was used
      for assessment of tissue damage caused by the currents. RESULTS: In the cutting
      mode, the ERBE ESG produced a mean stray current of 70 mA with an intact loop and
      144 mA with a loop having faulty insulation. The Valleylab ESG produced 150 mA
      and 161 mA, respectively. In the coagulation mode, the ERBE ESG produced an
      average leakage current of 35 mA and, with a loop with faulty insulation, 40 mA.
      The Valleylab ESG produced 148 mA and 151 mA, respectively. CONCLUSIONS:
      Electrical injury may represent a significant cause of urethral stricture after
      transurethral electrosurgery. The critical power density of 7.5 W/cm2 (which is
      likely to cause a urethral burn) may be reached, especially with the use of loops
      with faulty insulation or nonconductive lubricating gel. The ERBE ESG produced
      significantly less capacitance, decreasing the risk of urethral electrical burn.
      Conductive gel prevents dangerous current concentration.

PMID- 11325099
TI  - Generalized optical theorem for scatterers having inversion symmetry:
      applications to acoustic backscattering.
AB  - The far-field acoustic scattering amplitudes for the scattering of plane waves by
      targets having inversion symmetry obey a generalized optical theorem in the
      absence of dissipation. The theorem allows a component of the complex scattering
      amplitude in an arbitrary direction to be expressed in terms of an angular
      integration involving scattering amplitudes evaluated at different angles. The
      result reduces to the usual optical theorem in the case of forward scattering.
      The theorem is applied to the backscattering by a perfectly soft sphere as a
      numerical example. The relevant integrand is shown to be oscillatory. Some
      potential applications to inverse problems, multiple scattering, and the
      verification of numerical algorithms are noted.

PMID- 11325100
TI  - On the modeling of narrow gaps using the standard boundary element method.
AB  - Numerical methods based on the Helmholtz integral equation are well suited for
      solving acoustic scattering and diffraction problems at relatively low
      frequencies. However, it is well known that the standard method becomes
      degenerate if the objects that disturb the sound field are very thin. This paper
      makes use of a standard axisymmetric Helmholtz integral equation formulation and
      its boundary element method (BEM) implementation to study the behavior of the
      method on two test cases: a thin rigid disk of variable thickness and two rigid
      cylinders separated by a gap of variable width. Both problems give rise to the
      same kind of degeneracy in the method, and modified formulations have been
      proposed to overcome this difficulty. However, such techniques are better suited
      for the so-called thin-body problem than for the reciprocal narrow-gap problem,
      and only the first is usually dealt with in the literature. A simple integration
      technique that can extend the range of thicknesses/widths tractable by the
      otherwise unmodified standard formulation is presented and tested. This technique
      is valid for both cases. The modeling of acoustic transducers like sound
      intensity probes and condenser microphones has motivated this work, although the
      proposed technique has a wider range of applications.

PMID- 11325101
TI  - Wave reflections from duct terminations.
AB  - The reflection coefficients and inertial end corrections of several duct
      terminations, including finite length duct extensions perpendicular to an
      infinite wall, as well as at a number of angles, curved interface surfaces, and
      annular cavities, are determined and analyzed in the absence of flow by employing
      the boundary element method. Predictions for the classical unflanged and flanged
      circular ducts show good agreement with analytical and computational results
      available in the literature. The predictions for curved interface surfaces
      (bellmouth or horn) are also consistent with the available experimental data. In
      view of its high reflection coefficient, the duct termination with an annular
      cavity may be suggested for the suppression of noise radiation in a specific
      frequency band or for an effective wave reflection from the termination.

PMID- 11325102
TI  - Modeling of high-frequency scattering from objects using a hybrid
      Kirchhoff/diffraction approach.
AB  - In this paper a numerical discretization and transformation into the time domain
      of a hybrid Kirchhoff/diffraction method is presented for the modeling of high
      frequency pulse scattering from rigid bodies. A series of benchmark cases, for
      smooth and rough spheres and cylinders, is presented to establish the accuracy of
      the method in the time domain.

PMID- 11325103
TI  - Use of nonsingular boundary integral formulation for reducing errors due to near
      field measurements in the boundary element method based near-field acoustic
      holography.
AB  - In the conformal near-field acoustic holography (NAH) using the boundary element
      method (BEM), the transfer matrix relating the vibro-acoustic properties of
      source and field depends solely on the geometrical condition of the problem. This
      kind of NAH is known to be very powerful in dealing with the sources having
      irregular shaped boundaries. When the vibro-acoustic source field is
      reconstructed by using this conformal NAH, one tends to position the sensors as
      close as possible to the source surface in order to get rich information on the
      nonpropagating wave components. The conventional acoustic BEM based on the
      Kirchhoff-Helmholtz integral equation has the singularity problem in the close
      near field of the source surface. This problem stems from the singular kernel of
      the Green function of the boundary integral equation (BIE) and the singularity
      can influence the reconstruction accuracy greatly. In this paper, the nonsingular
      BIE is introduced to the NAH calculation and the holographic BIE is reformulated.
      The effectiveness of nonsingular BEM has been investigated for the reduction of
      reconstruction error. Through interior and exterior examples, it is shown that
      the resolution of predicted field pressure could be improved in the close near
      field by employing the nonsingular BIE. Because the BEM-based NAH inevitably
      requires the field pressure measured in the close proximity to the source
      surface, the present approach is recommended for improving the resolution of the
      reconstructed source field.

PMID- 11325104
TI  - A generalized Westervelt equation for nonlinear medical ultrasound.
AB  - A model equation is derived for nonlinear medical ultrasound. Unlike the existing
      models, which use spatial coordinates, material coordinates are used and hence a
      model for a heterogeneous medium is able to be derived. The equation is a
      generalization of the Westervelt equation, and includes the nonlinearity,
      relaxation, and heterogeneity of soft tissue. The validity of the generalized
      Westervelt equation as a model equation for a Piola-Kirchoff acoustic pressure
      and as an equation for the acoustic pressure is discussed. In the second case it
      turns out that the model follows from two geometric approximations which are
      valid when the radius of curvature of the phase fronts is much larger than the
      particle displacements. The model is exact for plane waves and includes arbitrary
      nonlinearity in the stress-strain relation.

PMID- 11325105
TI  - Vortex sound generation due to a flow impedance discontinuity on a flat surface.
AB  - The sound generated by the unsteady motion of a vortex filament moving over a
      flat boundary with a sharp flow impedance discontinuity is studied theoretically.
      Theoretical results show that the vortex filament undergoes significant
      accelerating or decelerating motions and radiates sound at the instant when it
      moves across the plane of impedance discontinuity. The accelerations and
      decelerations of the vortex filament are shown to be the major mechanisms of
      sound generation. The sound so produced has a large low-frequency content such
      that the change in the flow impedance affects only the sound generation process
      but not the subsequent sound propagation to the far field.

PMID- 11325106
TI  - A computational approach for flow-acoustic coupling in closed side branches.
AB  - The quarter-wave resonator, which produces a narrow band of high acoustic
      attenuation at regularly spaced frequency intervals, is a common type of silencer
      used in ducts. The presence of mean flow in the main duct, however, is likely to
      promote an interaction between these acoustic resonances and the flow. The
      coupling for some discrete flow conditions leads to the production of both large
      wave amplitudes in the side branch and high noise levels in the main duct,
      thereby transforming the quarter-wave silencer into a noise generator. The
      present approach employs computational fluid dynamics (CFD) to model this complex
      interaction between the flow and acoustic resonances at low Mach number by
      solving the unsteady, turbulent, and compressible Navier-Stokes equations.
      Comparisons between the present computations and the experiments of Ziada [PVP
      Vol. 258, ASME, 35-59 (1993)] for a system with two coaxial side branches show
      that the method is capable of reproducing the physics of the flow-acoustic
      coupling and predicting the flow conditions when the coupling occurs. The theory
      of Howe [IMA J. Appl. Math. 32, 187-209 (1984)] is then employed to determine the
      location and timing of the acoustic power production during a cycle.

PMID- 11325107
TI  - Matched field processing with data-derived modes.
AB  - The authors demonstrate MFP using data-derived modes and the sound speed profile,
      using no a priori bottom information. Mode shapes can be estimated directly from
      vertical line array data, without a priori knowledge of the environment and
      without using numerical wave field models. However, it is difficult to make much
      headway with data-derived modes alone, without wave numbers, since only a few
      modes at a few frequencies may be captured, and only at depths sampled by the
      array. Using a measured sound speed profile, the authors derive self-consistent,
      complete sets of modes, wave numbers, and bottom parameters from data-derived
      modes. Bottom parameters enable modes to be calculated at all frequencies, not
      just those at which modes were derived from data. This process is demonstrated on
      SWellEx-96 experiment data. Modes, wave numbers, and bottom parameters are
      derived from one track and MFP based on this information is demonstrated on
      another track.

PMID- 11325108
TI  - Acoustic transmission across a roughened fluid-fluid interface.
AB  - A set of tank experiments was performed to investigate acoustic transmission
      across a roughened fluid-fluid interface with the intention to test heuristic
      Bragg scattering predictions used to explain observations of anomalous
      transmission in field experiments. In the tank experiments, two immiscible fluids
      (vegetable oil floating on glycerin) formed the layers. Small polystyrene beads
      were floated at the interface to simulate roughness. An array of hydrophones
      placed in the bottom layer (glycerin) was used to measure the acoustic levels
      transmitted across the interface. This array was also employed as a beamformer to
      determine the apparent angle and sound speed of the scattered signals. Data were
      acquired at subcritical grazing angles in the frequency range of 100-200 kHz for
      three different bead diameters and for various configurations in which the
      locations of the beads floating on the interface were varied. Results of these
      measurements demonstrated that a significant amount of acoustic energy can be
      scattered into the bottom layer by beads floating at the interface. The scattered
      levels increased with increasing bead diameter. However, discrepancies occurred
      between observed propagation properties and the Bragg predictions. By comparing
      the processed tank data to a computer simulation of the same it was determined
      that these discrepancies are a consequence of near-field reception of the
      scattering by the bead array and ignoring the directionality of the scattering by
      the beads. Consequences to observations made in field experiments are discussed.

PMID- 11325109
TI  - Modeling of bottom backscattering from three-dimensional volume inhomogeneities
      and comparisons with experimental data.
AB  - In this paper, backscattering from 3D volume inhomogeneities in the seabed is
      modeled and the results compared with experimental data at 250-650 Hz. The
      experiment was part of the Acoustic Reverberation Special Research Program
      (ARSRP) and the data were obtained in a sediment pond on the western flank of the
      Mid-Atlantic Ridge. A volume scattering model based on first-order perturbation
      theory is developed incorporating contributions from both sound speed and density
      fluctuations. With the propagators, i.e., the Green's functions, handled
      accurately through numerical wave number integration and random fluctuations
      generated effectively by a new scheme modified from the spectral method, the
      model is capable of simulating monostatic, backscattered fields in the frequency
      domain as well as in the time domain owing to 3D volumetric sediment
      inhomogeneities. The model compares favorably and consistently with the ARSRP
      backscattering data over the entire frequency band, with the fluctuations of
      sound speed and density in two irregular sediment layers, identified from the
      data analysis, described by a power-law type of power spectrum.

PMID- 11325110
TI  - The explicit secular equation for surface acoustic waves in monoclinic elastic
      crystals.
AB  - The secular equation for surface acoustic waves propagating on a monoclinic
      elastic half-space is derived in a direct manner, using the method of first
      integrals. Although the motion is at first assumed to correspond to generalized
      plane strain, the analysis shows that only two components of the mechanical
      displacement and of the tractions on planes parallel to the free surface are
      nonzero. Using the Stroh formalism, a system of two second order differential
      equations is found for the remaining tractions. The secular equation is then
      obtained as a quartic for the squared wave speed. This explicit equation is
      consistent with that found in the orthorhombic case. The speed of subsonic
      surface waves is then computed for 12 specific monoclinic crystals.

PMID- 11325111
TI  - Finite-element modeling of lead magnesium niobate electrostrictive materials:
      dynamic analysis.
AB  - A finite-element model is proposed for the time-domain analysis of
      electrostrictive materials. Hom's material model, developed for lead magnesium
      niobate (PMN) ceramics, is used. It includes the quadratic dependence of strain
      with polarization, the saturation of polarization, assumes constant temperature,
      and excludes hysteresis. The theoretical formulation is justified by the
      principle of virtual works. The numerical model is obtained after discretization
      in space and time. The validation is performed by comparing numerical results
      with semianalytical results for an electrostrictive spherical shell subjected to
      a step in voltage or in charge. From these results, a method to compute the
      coupling coefficient of electrostrictive materials, based on Ikeda's definition,
      is proposed and applied to a bar with parallel electric field.

PMID- 11325112
TI  - New piezoelectric polymer for air-borne and water-borne sound transducers.
AB  - Acoustic transducers made of a charged cellular polymer called EMFi have been
      designed and investigated with respect to air-borne and water-borne sound. The
      longitudinal transducer constant is around 90 pC/N, strongly exceeding the values
      of other piezoelectric polymers. This is mainly attributed to the very low
      Young's modulus of about 2 MPa. The acoustic impedance is only 2.6 x 10(4) kg/(m2
      s) and results in good matching to air but strong loading under water. Due to
      this strong loading, a pronounced reduction of resonance frequency from 300 kHz
      in air down to 17 kHz under water is observed. The experiments indicate that
      fluid loading is not only mass-like but also compliant, reducing the transducer's
      sensitivity below the resonance frequency of about -63 dB re 1 V/Pa (0.7 mV/Pa)
      in air to -71 dB re 1 V/Pa under water. This compliance is attributed to the
      medium's compressibility. Piezoelectricity of EMFi films is limited to
      temperatures below 70 degrees C; above, irreversible discharge of trapped charges
      takes place. Furthermore, a second type of EMFi, called "OS" was investigated,
      having a piezoelectric constant of 15 pC/N and a Young's modulus of 6 MPa. In
      quasi-static sensor measurements, the piezoelectric constant increases with the
      applied load. This nonlinearity explains the higher values reported in other
      publications on the same materials.

PMID- 11325113
TI  - Wave transmission through structural inserts.
AB  - The transmission of waves through two discontinuities in a one-dimensional
      waveguide system is considered. Attention is focused on transmission through a
      structural insert, which is defined here to be a waveguide segment which is
      inserted into an otherwise continuous structural member with different
      properties. A general expression for the net transmission through the insert is
      found. It has bandpass/stop characteristics and its frequency average is somewhat
      greater than that normally assumed due to the coherent interaction of the waves
      in the insert. The particular case is then considered where the insert comprises
      a three-layer composite beam inserted in a thin beam which vibrates in bending.
      The composite beam comprises two elastic faceplates and a core filled with a
      tunable electro- or magneto-rheological fluid. The net transmission and the stop
      bands depend on the properties of the insert. Since these properties are tunable
      by adjusting the field to which the tunable fluid is exposed, then so too are the
      transmission characteristics of the insert.

PMID- 11325114
TI  - Time-domain simulation of damped impacted plates. I. Theory and experiments.
AB  - A time-domain formulation for the flexural vibrations in damped rectangular
      isotropic and orthotropic plates is developed, in order to investigate transient
      excitation of plates by means of sound synthesis. The model includes three basic
      mechanisms of damping (thermoelasticity, viscoelasticity and radiation) using a
      general differential operator. The four rigidity factors of the plate are
      modified by perturbation terms, each term corresponding to one specific damping
      mechanism. The first damping term is derived from the coupling between the
      thermoelastic stress-strain relations and the heat diffusion equation. The second
      term is obtained from the general differential formulation of viscoelasticity.
      The third term is obtained through a Pade approximation of the damping factor
      which governs the coupling of the plate with the surrounding air. The decay
      factors predicted by the model reproduce adequately the dependence on both
      dimensions and frequency of the decay factors measured on rectangular plates of
      various sizes and thicknesses made of four different materials (aluminum, glass,
      carbon fiber, and wood). The numerical resolution of the complete problem,
      including initial and boundary conditions, and the comparison between real and
      simulated sounds are presented in a companion paper.

PMID- 11325115
TI  - Time-domain simulation of damped impacted plates. II. Numerical model and
      results.
AB  - A time-domain model for the flexural vibrations of damped plates was presented in
      a companion paper [Part I, J. Acoust. Soc. Am. 109, 1422-1432 (2001)]. In this
      paper (Part II), the damped-plate model is extended to impact excitation, using
      Hertz's law of contact, and is solved numerically in order to synthesize sounds.
      The numerical method is based on the use of a finite-difference scheme of second
      order in time and fourth order in space. As a consequence of the damping terms,
      the stability and dispersion properties of this scheme are modified, compared to
      the undamped case. The numerical model is used for the time-domain simulation of
      vibrations and sounds produced by impact on isotropic and orthotropic plates made
      of various materials (aluminum, glass, carbon fiber and wood). The efficiency of
      the method is validated by comparisons with analytical and experimental data. The
      sounds produced show a high degree of similarity with real sounds and allow a
      clear recognition of each constitutive material of the plate without ambiguity.

PMID- 11325116
TI  - The influence of substructure modeling on the structural-acoustic response of a
      plate system.
AB  - Changes in the vibro-acoustic response of a fluid-loaded plate due to variations
      in some of the modeling details associated with an attached substructure are
      examined. The attached substructure consists of a smaller plate supported by
      springs along each edge. To examine the important modeling issues, three studies
      are performed. In the first study, discrete changes in the system response due to
      discrete changes in the size of the region over which the spring elasticity is
      distributed are examined. In the second study, substructure modeling issues are
      examined by varying the number of degrees-of-freedom included in the substructure
      model. Finally, sensitivity relationships that express changes in the system
      response to changes in the scale of the spring elements are developed. These
      relationships are used to examine changes in the system response due to small
      variations in the scale of the distributed elasticity. Both the combined system
      response and acoustic radiation are computed using the Acoustic Surface
      Variational Principle and Hamilton's Principle. For the example cases considered,
      it is shown that details associated with the scale of the spring are only
      important for frequencies near or below the resonances of the isolated subsystem.
      Furthermore, only the dynamics of the substructure including rigid-body type
      motions are important.

PMID- 11325117
TI  - Noise transmission from a curved panel into a cylindrical enclosure: analysis of
      structural acoustic coupling.
AB  - Much of the research on sound transmission through the aircraft fuselage into the
      interior of aircraft has considered coupling of the entire cylinder to the
      acoustic modes of the enclosure. Yet, much of the work on structural acoustic
      control of sound radiation has focused on reducing sound radiation from
      individual panels into an acoustic space. Research by the authors seeks to bridge
      this gap by considering the transmission of sound from individual panels on the
      fuselage to the interior of the aircraft. As part of this research, an analytical
      model of a curved panel, with attached piezoelectric actuators, subjected to a
      static pressure load was previously developed. In the present work, the
      analytical model is extended to consider the coupling of a curved panel to the
      interior acoustics of a rigid-walled cylinder. Insight gained from an accurate
      analytical model of the dynamics of the noise transmission from the curved panels
      of the fuselage into the cylindrical enclosure of an aircraft is essential to the
      development of feedback control systems for the control of stochastic inputs,
      such as turbulent boundary layer excitation. The criteria for maximal structural
      acoustic coupling between the modes of the curved panel and the modes of the
      cylindrical enclosure are studied. For panels with aspect ratios typical of those
      found in aircraft, results indicate that predominately axial structural modes
      couple most efficiently to the acoustic modes of the enclosure. The effects of
      the position of the curved panel on the cylinder are also studied. Structural
      acoustic coupling is found to not be significantly affected by varying panel
      position. The impact of the findings of this study on structural acoustic control
      design is discussed.

PMID- 11325118
TI  - Psychoacoustic correlates of individual noise sensitivity.
AB  - In environmental noise surveys, self-reported noise sensitivity, a stable
      personality trait covering attitudes toward a wide range of environmental sounds,
      is a major predictor of individual noise-annoyance reactions. Its relationship to
      basic measures of auditory functioning, however, has not been systematically
      explored. Therefore, in the present investigation, a sample of 61 unselected
      listeners was subjected to a battery of psychoacoustic procedures ranging from
      threshold determinations to loudness scaling tasks. No significant differences in
      absolute thresholds, intensity discrimination, simple auditory reaction time, or
      power-function exponents for loudness emerged, when the sample was split along
      the median into two groups of "low" vs "high" noise sensitivity on the basis of
      scores obtained from a psychometrically evaluated questionnaire [Zimmer and
      Ellermeier, Diagnostica 44, 11-20 (1998)]. Small, but systematic differences were
      found in verbal loudness estimates, and in ratings of the unpleasantness of
      natural sounds, thus suggesting that self-reported noise sensitivity captures
      evaluative rather than sensory aspects of auditory processing.

PMID- 11325119
TI  - Predicting speech metrics in a simulated classroom with varied sound absorption.
AB  - By systematically varying the amount of sound absorption, and the location of the
      sound-absorbing material in a simulated classroom, it was possible to assess the
      accuracy of the prediction of speech metrics in quite simple acoustical
      environments. Predictions of speech level, early-to-late sound ratios (C50) and
      speech transmission index (STI) values were obtained analytically and with two
      hybrid ray-based computer programs, RAYNOISE 3.0 and ODEON 4.1. The RAYNOISE
      predictions were accomplished with a purely specular reflection model and also
      with a calibrated diffuse reflection model. ODEON uses a parameter called
      transition order, TO, to change the reflection procedure from purely specular to
      diffuse for reflections that have orders higher than TO. A parametric study was
      conducted to determine the best transition order for the ODEON prediction of
      speech metrics. It was found that the analytical predictions of speech level and
      C50 were on average accurate to about 1 just-noticeable difference (jnd), whereas
      the analytical predictions of STI were on average within 2 jnd's. ODEON
      predictions of speech level, C50 and STI were on average within 2 jnd's. RAYNOISE
      predictions of C50 and STI with the specular model were on average within 2
      jnd's. However, the RAYNOISE predictions of speech level, with both types of
      reflection models, and the RAYNOISE predictions of C50 and STI with the diffuse
      model had average errors greater than 2 jnd's. The effects of the sound
      absorption treatments on the measured speech metric values are also discussed.

PMID- 11325120
TI  - Structure-borne noise reduction for an infinite, elastic cylindrical shell.
AB  - A theoretical model was developed to evaluate the reduction of structure-borne
      noise generated by an axially symmetric ring force which is applied on the
      interior of the cylindrical shell. The vibrating cylindrical shell is coated with
      a microvoided elastomer that is acoustically soft material designed for the
      reduction of the generated noise. The analytical model is a two-layer shell
      structure comprised of a cylindrical shell and an outer layer (coating) that is
      perfectly bonded to the cylindrical shell. The outer and inner surfaces of the
      coated shell are in contact with water and air, respectively. The analysis for
      this problem is based on the theory of elasticity, acoustic wave equations, and
      pertinent boundary conditions. Effects of various parameters such as coating
      thickness and material properties on the noise reductions are presented.

PMID- 11325121
TI  - Suppression of distortion product otoacoustic emissions and hearing threshold.
AB  - A distortion product otoacoustic emission (DPOAE) suppression tuning curve (STC)
      shows the minimum level of suppressor tone that is required to reduce DPOAE level
      by a fixed amount, as a function of suppressor frequency. Several years ago,
      Mills [J. Acoust. Soc. Am. 103, 507-523 (1998)] derived, theoretically, an
      approximately linear relationship between the tip-to-tail suppressor level
      difference on a DPOAE STC, and the gain of the cochlear amplifier, defined as the
      maximum increase in the active over the passive basilar membrane (BM) response.
      In this paper, preliminary data from adult human subjects are presented that
      establish a correlation between this tip-to-tail DPOAE STC difference and the
      threshold of hearing, the latter measured at the frequency of the f2 primary
      tone. Assuming that both suppression and the DPOAE are by-products of active,
      nonlinear BM dynamics, the above result suggests that threshold elevation in mild
      levels of hearing loss may be attributed, in part, to a reduction of cochlear
      amplifier gain, which is detectable with the suppression paradigm.

PMID- 11325122
TI  - DPOAE group delays versus electrophysiological measures of cochlear delay in
      normal human ears.
AB  - Group delays of 2 f1-f2 distortion product otoacoustic emissions (DPOAEs) were
      determined using both f1- and f2-sweep paradigms in 24 normal-hearing subjects.
      These DPOAE group delays were studied in comparison with cochlear delays
      estimated from derived band VIIIth nerve compound action potentials (CAPs) and
      auditory brainstem responses (ABRs) in the same subjects. The center frequencies
      of the derived bands in the electrophysiological experiment were matched with the
      f2-frequencies in the DPOAE recording to ensure that DPOAEs and derived CAPs and
      ABRs were generated at the same places along the cochlear partition, thus
      allowing for a direct comparison. The degree to which DPOAE group delays are
      larger in the f2- than in the f1-sweep paradigm is consistent with a theoretical
      analysis of the so-called wave-fixed model. Both DPOAE group delays are highly
      correlated with CAP- and ABR-derived measures of cochlear delay. The principal
      result of this study is that "roundtrip" DPOAE group delay in the f1-sweep
      paradigm is exactly twice as large as the neural estimate of the "forward"
      cochlear delay. The interpretation of this notion in the context of cochlear wave
      propagation properties and DPOAE-generating mechanisms is discussed.

PMID- 11325123
TI  - Wave and place fixed DPOAE maps of the human ear.
AB  - Human intermodulation distortion product otoacoustic emissions (DPOAE) can be a
      mixture of low and high latency components. They have different level, phase, and
      suppression characteristics, which indicate that emissions arise both from the
      frequency region of the primary tones directly and indirectly via the DP
      frequency place. Which component dominates the measured DPOAE in the ear canal
      depends on the stimulus parameters, especially the frequency ratio, f2/f1.
      Interference between the two emissions adds complexity to measurements of DPOAE.
      The behavior and even existence of whichever emission route is lower in level
      often cannot directly be deduced from the raw DPOAE data because the other
      emission covers it. It is therefore not known whether both emissions are present
      for all stimulus parameters or whether the trends seen in each emission when they
      are the dominant emission route continue under stimulus conditions when they are
      not dominant. In this study, the two DPOAE components are separated by a post
      processing method. Previously, maps of raw DPOAE data against f2/f1 and DP
      frequency have been obtained. To separate the components, sets of data consisting
      of f2/f1 sweeps were transformed by an inverse Fourier transform into the time
      domain. The low and high latency components appeared as two distinct peaks
      because of their different phase gradients. These peaks were separated by
      windowing in the time domain and two frequency domain maps were reconstructed,
      representing the low and high latency DPOAEs. It was found that the low latency
      component of the 2 f1-f2 DP was only emitted strongly with f2/f1 between
      approximately 1.1 and 1.3. The removal of the high latency component revealed the
      low ratio edge of this region, at which the level falls sharply. However, the low
      latency emission has been traced at reduced amplitude over a wide range of
      stimulus parameters. Although previously only observed at small frequency ratios,
      the high latency component was found to be present widely in the lower sideband,
      its level reducing slowly at larger f2/f1. Its phase behavior changes in the
      lower sideband, being approximately constant with DP frequency at small ratios of
      f2/f1, but deviating from this at wider ratios. These results support the
      hypothesis that a DPOAE component which propagates to and is re-emitted from the
      DP frequency place (place fixed emission) is present across a wide parameter
      range. However, for all but the close primary condition the lower sideband DPOAE
      is dominated by direct emission from the region of f2 and f1 wave interaction
      (wave fixed emission). A simple transmission line model is presented to
      illustrate how the observed DPOAE maps can arise on the basis of this hypothesis.

PMID- 11325124
TI  - Effects of stimulus frequency and complexity on the mismatch negativity and other
      components of the cortical auditory-evoked potential.
AB  - This study investigated, first, the effect of stimulus frequency on mismatch
      negativity (MMN), N1, and P2 components of the cortical auditory event-related
      potential (ERP) evoked during passive listening to an oddball sequence. The
      hypothesis was that these components would show frequency-related changes,
      reflected in their latency and magnitude. Second, the effect of stimulus
      complexity on those same ERPs was investigated using words and consonant-vowel
      tokens (CVs) discriminated on the basis of formant change. Twelve normally
      hearing listeners were tested with tone bursts in the speech frequency range
      (400/440, 1,500/1,650, and 3,000/3,300 Hz), words (/baed/ vs /daed/) and CVs
      (/bae/ vs /dae/). N1 amplitude and latency decreased as frequency increased. P2
      amplitude, but not latency, decreased as frequency increased. Frequency-related
      changes in MMN were similar to those for N1, resulting in a larger MMN area to
      low frequency contrasts. N1 amplitude and latency for speech sounds were similar
      to those found for low tones but MMN had a smaller area. Overall, MMN was present
      in 46%-71% of tests for tone contrasts but for only 25%-32% of speech contrasts.
      The magnitude of N1 and MMN for tones appear to be closely related, and both
      reflect the tonotopicity of the auditory cortex.

PMID- 11325125
TI  - Monaural masking release in random-phase and low-noise noise.
AB  - Two masking-release paradigms thought to involve across-channel processing are
      comodulation masking release (CMR) and profile analysis. Similarities between
      these two paradigms were explored by comparing signal detection in maskers that
      varied only in degree of envelope fluctuation. The narrow-band-noise maskers were
      10 Hz wide and their envelope fluctuations were manipulated using the low-noise
      noise algorithm of Pumplin [J. Acoust. Soc. Am. 78, 100-104 (1985)]. Masking
      conditions included the classic CMR conditions of an on-frequency band, multiple
      (five) incoherent bands, or multiple coherent bands. Detection was compared using
      both random-phase noise (RPN) and low-noise noise (LNN) maskers. In one set of
      conditions, the signal was identical to the on-frequency masker, yielding an
      intensity discrimination task. Conditions that included RPN maskers and tonal
      signals resembled the classic CMR paradigm, whereas conditions including LNN and
      noise signals more closely resembled the classic profile analysis paradigm. Other
      conditions may be considered hybrids. This combination of conditions provided a
      wide variety of within- and across-channel cues for detection. The results
      suggest that CMR and profile analysis could be based upon the same set of
      stimulus cues and perhaps the same perceptual processes.

PMID- 11325126
TI  - Measurement of auditory temporal processing using modified masking period
      patterns.
AB  - A common metric of auditory temporal processing is the difference in the
      threshold for a pure-tone signal masked by either unmodulated or amplitude
      modulated noise. This technique may be viewed as a modification of the masking
      period pattern technique. Such measurements have been proposed as an efficient
      means of estimating auditory temporal resolution in a clinical setting, although
      in many cases threshold differences may reflect additional spectro-temporal
      processes. The primary purpose of the present experiment was to examine
      interactions among signal frequency and masker bandwidth and the effects of
      modulation frequency on modified masking period patterns. The results revealed
      unmodulated-modulated threshold differences that increased with increasing masker
      bandwidth and decreased with increasing modulation frequency. There was little
      effect of signal frequency for narrow-band noise maskers that were equal in
      absolute bandwidth across frequency. However, unmodulated-modulated threshold
      differences increased substantially with increasing signal frequency for
      bandwidths proportional to the signal frequency and for wideband maskers.
      Although the results are interpreted in terms of a combination of both within
      channel and across-channel cues, the specific contributions of these cues in
      particular conditions are difficult to ascertain. Because modified masking period
      patterns depend strongly upon a number of specific stimulus parameters, and
      because it is difficult to determine with any precision the underlying perceptual
      processes, this technique is not recommended for use as a clinical measure of
      auditory temporal processing.

PMID- 11325127
TI  - Functional magnetic resonance imaging measurements of sound-level encoding in the
      absence of background scanner noise.
AB  - Effects of sound level on auditory cortical activation are seen in neuroimaging
      data. However, factors such as the cortical response to the intense ambient
      scanner noise and to the bandwidth of the acoustic stimuli will both confound
      precise quantification and interpretation of such sound-level effects. The
      present study used temporally "sparse" imaging to reduce effects of scanner
      noise. To achieve control for stimulus bandwidth, three schemes were compared for
      sound-level matching across bandwidth: component level, root-mean-square power
      and loudness. The calculation of the loudness match was based on the model
      reported by Moore and Glasberg [Acta Acust. 82, 335-345 (1996)]. Ten normally
      hearing volunteers were scanned using functional magnetic resonance imaging
      (tMRI) while listening to a 300-Hz tone presented at six different sound levels
      between 66 and 91 dB SPL and a harmonic-complex tone (F0= 186 Hz) presented at 65
      and 85 dB SPL. This range of sound levels encompassed all three bases of sound
      level matching. Activation in the superior temporal gyrus, induced by each of the
      eight tone conditions relative to a quiet baseline condition, was quantified as
      to extent and magnitude. Sound level had a small, but significant, effect on the
      extent of activation for the pure tone, but not for the harmonic-complex tone,
      while it had a significant effect on the response magnitude for both types of
      stimulus. Response magnitude increased linearly as a function of sound level for
      the full range of levels for the pure tone. The harmonic-complex tone produced
      greater activation than the pure tone, irrespective of the matching scheme for
      sound level, indicating that bandwidth had a greater effect on the pattern of
      auditory activation than sound level. Nevertheless, when the data were collapsed
      across stimulus class, extent and magnitude were significantly correlated with
      the loudness scale (measured in phons), but not with the intensity scale
      (measured in SPL). We therefore recommend the loudness formula as the most
      appropriate basis of matching sound level to control for loudness effects when
      cortical responses to other stimulus attributes, such as stimulus class, are the
      principal concern.

PMID- 11325128
TI  - The effect of basilar-membrane nonlinearity on the shapes of masking period
      patterns in normal and impaired hearing.
AB  - Masking period patterns (MPPs) were measured in listeners with normal and
      impaired hearing using amplitude-modulated tonal maskers and short tonal probes.
      The frequency of the masker was either the same as the frequency of the probe (on
      frequency masking) or was one octave below the frequency of the probe (off
      frequency masking). In experiment 1, MPPs were measured for listeners with normal
      hearing using different masker levels. Carrier frequencies of 3 and 6 kHz were
      used for the masker. The probe had a frequency of 6 kHz. For all masker levels,
      the off-frequency MPPs exhibited deeper and longer valleys compared with the on
      frequency MPPs. Hearing-impaired listeners were tested in experiment 2. For some
      hearing-impaired subjects, masker frequencies of 1.5 kHz and 3 kHz were paired
      with a probe frequency of 3 kHz. MPPs measured for listeners with hearing loss
      had similar shapes for on- and off-frequency maskers. It was hypothesized that
      the shapes of MPPs reflect nonlinear processing at the level of the basilar
      membrane in normal hearing and more linear processing in impaired hearing. A
      model assuming different cochlear gains for normal versus impaired hearing and
      similar parameters of the temporal integrator for both groups of listeners
      successfully predicted the MPPs.

PMID- 11325129
TI  - Gap detection for similar and dissimilar gap markers.
AB  - Detection thresholds for temporal gaps between markers of dissimilar frequency
      are usually elevated with respect to thresholds for gaps between markers of
      similar frequency. Because gaps between markers of dissimilar frequency represent
      both a spectrally based perceptual discontinuity as well as a temporal
      discontinuity, it is not clear what factors underlie the threshold elevation.
      This study sought to examine the effects of perceptual dissimilarities on gap
      detection. The first experiment measured gap detection for configurations of
      narrow-band gap markers comprised of pure tones, frequency-modulated tones, and
      amplitude-modulated tones. The results showed that gap thresholds for frequency
      disparate pure-tone markers were elevated with respect to isofrequency tonal
      markers, but that perceptual discontinuities between markers restricted to the
      same frequency region did not uniformly elevate threshold. The second experiment
      measured gap detection for configurations of markers where the leading and
      trailing markers could differ along the dimensions of bandwidth, duration, and
      pitch. The results showed that, in most cases, gap detection deteriorated when
      the bandwidth of the two markers differed, even when the spectral content of the
      narrower-band marker was completely subsumed by the spectral content of the wider
      band marker. This finding suggests that gap detection is sensitive to spectral
      dissimilarity between markers in addition to spectral discontinuity. The effects
      of marker duration depended on the marker bandwidth. Pitch differences across
      spectrally similar markers had no effect.

PMID- 11325130
TI  - The contribution of two ears to the perception of vertical angle in sagittal
      planes.
AB  - Because the input signals to the left and right ears are not identical, it is
      important to clarify the role of these signals in the perception of the vertical
      angle of a sound source at any position in the upper hemisphere. To obtain basic
      findings on upper hemisphere localization, this paper investigates the
      contribution of each pinna to the perception of vertical angle. Tests measured
      localization of the vertical angle in five planes parallel to the median plane.
      In the localization tests, the pinna cavities of one or both ears were occluded.
      Results showed that pinna cavities of both the near and far ears play a role in
      determining the perceived vertical angle of a sound source in any plane,
      including the median plane. As a sound source shifts laterally away from the
      median plane, the contribution of the near ear increases and, conversely, that of
      the far ear decreases. For saggital planes at azimuths greater than 60 degrees
      from midline, the far ear no longer contributes measurably to the determination
      of vertical angle.

PMID- 11325131
TI  - Sensitivity to brief changes of interaural time and interaural intensity.
AB  - The purpose of this study was to measure listeners' abilities to detect brief
      changes in interaural temporal disparities (ITDs) or interaural intensitive
      disparities (IIDs) conveyed by bursts of noise (probes) temporally and
      symmetrically flanked by segments of diotic or uncorrelated noise. Thresholds
      were measured using a four-interval, two-alternative, forced-choice adaptive task
      and the total duration of the bursts of noise was either 20, 40, or 100 ms.
      Probes were temporally centered within each burst and the durations of the probes
      ranged from 2 to 100 ms, depending upon the duration of the (longer) total burst
      of noise within which they were embedded. The results indicate that, for a given
      total duration of noise, there is a rapid decrease in threshold ITD or threshold
      IID as the duration of the probe is increased so that it occupies a larger
      portion of the total burst of noise. Mathematical analyses revealed that both
      threshold ITDs and threshold IIDs could be well accounted for by assuming that
      the listener processes both types of binaural cues via a single, symmetric,
      double-exponential temporal window. Interestingly, the shapes of the temporal
      windows that fit the data obtained from the human listeners resemble the shapes
      of the temporal windows derived by Wagner [H. Wagner, J. Comp. Physiol. A 169,
      281-289 (1991)], who studied the barn owl. The time constants and relative
      weightings yielded temporal window functions that heavily emphasize information
      occurring within the very temporal center of the window. This temporal window
      function was found to be generalizable in the sense that it also accounts for
      classic data reported by Grantham and Wightman [D.W. Gratham and F.L. Wightman,
      J. Acoust. Soc. Am. 63, 511-523 (1978)] concerning sensitivity to dynamically
      changing interaural disparities.

PMID- 11325132
TI  - Intraglottal pressure profiles for a symmetric and oblique glottis with a
      divergence angle of 10 degrees.
AB  - Human phonation does not always involve symmetric motions of the two vocal folds.
      Asymmetric motions can create slanted or oblique glottal angles. This study
      reports intraglottal pressure profiles for a Plexiglas model of the larynx with a
      glottis having a 10-degree divergence angle and either a symmetric orientation or
      an oblique angle of 15 degrees. For the oblique glottis, one side was divergent
      and the other convergent. The vocal fold surfaces had 14 pressure taps. The
      minimal glottal diameter was held constant at 0.04 cm. Results indicated that for
      either the symmetric or oblique case, the pressure profiles were different on the
      two sides of the glottis except for the symmetric geometry for a transglottal
      pressure of 3 cm H2O. For the symmetric case, flow separation created lower
      pressures on the side where the flow stayed attached to the wall, and the largest
      pressure differences between the two sides of the channel were 5%-6% of the
      transglottal pressure. For the oblique case, pressures were lower on the
      divergent glottal side near the glottal entry and exit, and the cross-channel
      pressures at the glottis entrance differed by 27% of the transglottal pressure.
      The empirical pressure distributions were supported by computational results. The
      observed aerodynamic asymmetries could be a factor contributing to normal jitter
      values and differences in vocal fold phasing.

PMID- 11325133
TI  - Stochastic models of jitter.
AB  - This study presents stochastic models of jitter. Jitter designates small, random,
      involuntary perturbations of the glottal cycle lengths. Jitter is a base-line
      phenomenon that may be observed in all voiced speech sounds. Knowledge of its
      properties is therefore relevant to the acoustic modeling, analysis, and
      synthesis of voice quality. Also, models of jitter are conceptual frameworks that
      enable experimenters and clinicians to distinguish jitter in particular from
      aperiodic cycle length patterns in general. Vocal jitter is modeled by means of
      the ribbon model of the glottal vibration combined with stochastic models of the
      disturbances of the instantaneous frequency. The disturbance model comprises
      correlation-free noise and vocal microtremor. Properties of jitter that are
      simulated are the stochasticity, stationarity, and normality of the decorrelated
      cycle length perturbations, the size of decorrelated jitter, the correlation
      between the perturbations of neighboring glottal cycles, the modulation level and
      modulation frequency owing to microtremor, the asynchrony between external
      disturbances and glottal cycles, the dependence of the size of jitter on the
      average glottal cycle length, and the relation between jitter and laryngeal
      pathologies. Modeled jitter is discussed in the light of measured jitter, as well
      as the physiological and statistical plausibility of the model parameters.

PMID- 11325134
TI  - The relationship of vocal tract shape to three voice qualities.
AB  - Three-dimensional vocal tract shapes and consequent area functions representing
      the vowels [i, ae, a, u] have been obtained from one male and one female speaker
      using magnetic resonance imaging (MRI). The two speakers were trained vocal
      performers and both were adept at manipulation of vocal tract shape to alter
      voice quality. Each vowel was performed three times, each with one of the three
      voice qualities: normal, yawny, and twangy. The purpose of the study was to
      determine some ways in which the vocal tract shape can be manipulated to alter
      voice quality while retaining a desired phonetic quality. To summarize any
      overall tract shaping tendencies mean area functions were subsequently computed
      across the four vowels produced within each specific voice quality. Relative to
      normal speech, both the vowel area functions and mean area functions showed, in
      general, that the oral cavity is widened and tract length increased for the yawny
      productions. The twangy vowels were characterized by shortened tract length,
      widened lip opening, and a slightly constricted oral cavity. The resulting
      acoustic characteristics of these articulatory alterations consisted of the first
      two formants (F1 and F2) being close together for all yawny vowels and far apart
      for all the twangy vowels.

PMID- 11325135
TI  - Influence of emotion and focus location on prosody in matched statements and
      questions.
AB  - Preliminary data were collected on how emotional qualities of the voice (sad,
      happy, angry) influence the acoustic underpinnings of neutral sentences varying
      in location of intra-sentential focus (initial, final, no) and utterance
      "modality" (statement, question). Short (six syllable) and long (ten syllable)
      utterances exhibiting varying combinations of emotion, focus, and modality
      characteristics were analyzed for eight elderly speakers following administration
      of a controlled elicitation paradigm (story completion) and a speaker evaluation
      procedure. Duration and fundamental frequency (f0) parameters of recordings were
      scrutinized for "keyword" vowels within each token and for whole utterances.
      Results generally re-affirmed past accounts of how duration and f0 are encoded on
      key content words to mark linguistic focus in affectively neutral statements and
      questions for English. Acoustic data on three "global" parameters of the stimuli
      (speech rate, mean f0, f0 range) were also largely supportive of previous
      descriptions of how happy, sad, angry, and neutral utterances are differentiated
      in the speech signal. Important interactions between emotional and linguistic
      properties of the utterances emerged which were predominantly (although not
      exclusively) tied to the modulation of f0; speakers were notably constrained in
      conditions which required them to manipulate f0 parameters to express emotional
      and nonemotional intentions conjointly. Sentence length also had a meaningful
      impact on some of the measures gathered.

PMID- 11325136
TI  - A study of sentence stress production in Mandarin speakers of American English.
AB  - Acoustic characteristics of American English sentence stress produced by native
      Mandarin speakers are reported. Fundamental frequency (F0), vowel duration, and
      vowel intensity in the sentence-level stress produced by 40 Mandarin speakers
      were compared to those of 40 American English speakers. Results obtained from two
      methods of stress calculation indicated that Mandarin speakers of American
      English are able to differentiate stressed and unstressed words according to
      features of F0, duration, and intensity. Although the group of Mandarin speakers
      were able to signal stress in their sentence productions, the acoustic
      characteristics of stress were not identical to the American speakers. Mandarin
      speakers were found to produce stressed words with a significantly higher F0 and
      shorter duration compared to the American speakers. The groups also differed in
      production of unstressed words with Mandarin speakers using a higher F0 and
      greater intensity compared to American speakers. Although the acoustic
      differences observed may reflect an interference of L1 Mandarin in the production
      of L2 American English, the outcome of this study suggests no critical divergence
      between these speakers in the way they implement American English sentence
      stress.

PMID- 11325137
TI  - Effects of consonantal context on perceptual assimilation of American English
      vowels by Japanese listeners.
AB  - This study investigated the extent to which adult Japanese listeners' perceived
      phonetic similarity of American English (AE) and Japanese (J) vowels varied with
      consonantal context. Four AE speakers produced multiple instances of the 11 AE
      vowels in six syllabic contexts /b-b, b-p, d-d, d-t, g-g, g-k/ embedded in a
      short carrier sentence. Twenty-four native speakers of Japanese were asked to
      categorize each vowel utterance as most similar to one of 18 Japanese categories
      [five one-mora vowels, five two-mora vowels, plus/ei, ou/ and one-mora and two
      mora vowels in palatalized consonant CV syllables, C(j)a(a), C(j)u(u), C(j)o(o)].
      They then rated the "category goodness" of the AE vowel to the selected Japanese
      category on a seven-point scale. None of the 11 AE vowels was assimilated
      unanimously to a single J response category in all context/speaker conditions;
      consistency in selecting a single response category ranged from 77% for /eI/ to
      only 32% for /ae/. Median ratings of category goodness for modal response
      categories were somewhat restricted overall, ranging from 5 to 3. Results
      indicated that temporal assimilation patterns (judged similarity to one-mora
      versus two-mora Japanese categories) differed as a function of the voicing of the
      final consonant, especially for the AE vowels, /see text/. Patterns of spectral
      assimilation (judged similarity to the five J vowel qualities) of /see text/ also
      varied systematically with consonantal context and speakers. On the basis of
      these results, it was predicted that relative difficulty in the identification
      and discrimination of AE vowels by Japanese speakers would vary significantly as
      a function of the contexts in which they were produced and presented.

PMID- 11325138
TI  - Evidence for an analytic perception of multiharmonic sounds in the bat, Megaderma
      lyra, and its possible role for echo spectral analysis.
AB  - For echolocation, the gleaning bat Megaderma lyra relies on short and broadband
      calls consisting of multiple harmonic components, each of which is downward
      frequency modulated. The harmonic components in M. lyra's calls have a relatively
      small frequency excursion and do not overlap spectrally. Broadband calls of other
      bat species, on the other hand, often consist of only a few harmonics which are
      modulated over broad and sometimes overlapping frequency ranges. A call
      consisting of narrow and nonoverlapping harmonic components may provide a less
      complete representation of target structure than a call which consists of broadly
      modulated components. However, a multiharmonic call may help the bats to perceive
      local spectral changes in the echo from shifts in the peak frequencies of single
      harmonics, and thereby to extract additional information about the target. To
      assess this hypothesis, the accuracy with which M. lyra can analyze frequency
      shifts of single partials in multiharmonic complex tones was investigated. A two
      alternative, forced-choice behavioral task was used to measure M. lyra's
      frequency discrimination threshold for the third partial in complex tones whose
      spectral composition resembled that of the bat's sonar calls. The discrimination
      threshold for the third partial in a 21.5-kHz harmonic tone amounted to about 2%
      and was similar to the bat's pure-tone discrimination threshold at 64.5 kHz.
      Discrimination performance was essentially unaffected by random frequency changes
      of the other partials and by reducing stimulus duration from 50.5 to 1.5 ms. Both
      findings are in accordance with predictions made on the basis of the shape of M.
      Ivra's cochlear filters. The comparison between the observed frequency
      discrimination performance and a computational estimate of the expected frequency
      shift in the third harmonic of an echo reflected by a simple, two-front target
      showed that M. lyra's frequency resolution is sufficient for analyzing the target
      specific information conveyed by shifts in the peak frequency of single echo
      components.

PMID- 11325139
TI  - Assessment of dolphin (Tursiops truncatus) auditory sensitivity and hearing loss
      using jawphones.
AB  - Devices known as jawphones have previously been used to measure interaural time
      and intensity discrimination in dolphins. This study introduces their use for
      measuring hearing sensitivity in dolphins. Auditory thresholds were measured
      behaviorally against natural background noise for two bottlenose dolphins
      (Tursiops truncatus); a 14-year-old female and a 33-year-old male. Stimuli were
      delivered to each ear independently by placing jawphones directly over the pan
      bone of the dolphin's lower jaw, the assumed site of best reception. The shape of
      the female dolphin's auditory functions, including comparison measurements made
      in the free field, favorably matches that of the accepted standard audiogram for
      the species. Thresholds previously measured for the male dolphin at 26 years of
      age indicated a sensitivity difference between the ears of 2-3 dB between 4-10
      kHz, which was considered unremarkable at the time. Thresholds for the male
      dolphin reported in this study suggest a high-frequency loss compared to the
      standard audiogram. Both of the male's ears have lost sensitivity to frequencies
      above 55 kHz and the right ear is 16-33 dB less sensitive than the left ear over
      the 10-40 kHz range, suggesting that males of the species may lose sensitivity as
      a function of age. The results of this study support the use of jawphones for the
      measurement of dolphin auditory sensitivity.

PMID- 11325140
TI  - Comparison between visual and passive acoustic detection of finless porpoises in
      the Yangtze River, China.
AB  - Recently, sonar signals and other sounds produced by cetaceans have been used for
      acoustic detection of individuals and groups in the wild. However, the detection
      probability ascertained by concomitant visual survey has not been demonstrated
      extensively. The finless porpoises (Neophocaena phocaenoides) have narrow band
      and high-frequency sonar signals, which are distinctive from background noises.
      Underwater sound monitoring with hydrophones (B&K8103) placed along the sides of
      a research vessel, concurrent with visual observations was conducted in the
      Yangtze River from Wuhan to Poyang Lake in 1998 in China. The peak to peak
      detection threshold was set at 133 dB re 1 ,EPa. With this threshold level,
      porpoises could be detected reliably within 300 m of the hydrophone. In a total
      of 774-km cruise, 588 finless porpoises were sighted by visual observation and 44
      ,864 ultrasonic pulses were recorded by the acoustical observation system. The
      acoustic monitoring system could detect the presence of the finless porpoises 82%
      of the time. A false alarm in the system occurred with a frequency of 0.9%. The
      high-frequency acoustical observation is suggested as an effective method for
      field surveys of small cetaceans, which produce high-frequency sonar signals.

PMID- 11325141
TI  - The acoustic calls of blue whales off California with gender data.
AB  - The acoustic calls of blue whales off California are described with visual
      observations of behavior and with acoustic tracking. Acoustic call data with
      corresponding position tracks are analyzed for five calling blue whales during
      one 100-min time period. Three of the five animals produced type A-B calls while
      two produced another call type which we refer to as type D. One of the animals
      producing the A-B call type was identified as male. Pauses in call production
      corresponded to visually observed breathing intervals. There was no apparent
      coordination between the calling whales. The average call source level was
      calculated to be 186 dB re: 1 muPa at 1 m over the 10-110-Hz band for the type B
      calls. On two separate days, female blue whales were observed to be silent during
      respective monitoring periods of 20 min and 1 h.

PMID- 11325142
TI  - Surface acoustic impedance and causality.

PMID- 11325143
TI  - An updated perspective on basin-scale tomography.

PMID- 11325144
TI  - On the group velocity of guided waves in drill strings.

PMID- 11325145
TI  - On the modeling of the vent path in hearing aid systems.

PMID- 11325146
TI  - Women in dentistry.

PMID- 11325147
TI  - Special care dentistry.

PMID- 11325149
TI  - Prosthetic parts.

PMID- 11325148
TI  - Fracture causes cyst.

PMID- 11325150
TI  - Prescribing patients out of hours.

PMID- 11325151
TI  - Time for treatment.

PMID- 11325152
TI  - Seeking families with missing teeth.

PMID- 11325153
TI  - A sense of balance [interview by Fiona Stuart-Wilson].

PMID- 11325154
TI  - Tooth preparation.
AB  - This final article in the series describes the modification of teeth to improve
      their shape for the support and retention of RPDs.

PMID- 11325155
TI  - The contribution of imaging and digitised data to mandibular reconstruction and
      implant stabilised occlusal rehabilitation: a case report.
AB  - Different methods are recommended for the surgical reconstruction of the resected
      mandible. The advantages for implant stabilised prostheses in restoring the
      occlusion are recognised but few papers provide adequate data to identify the
      successful outcome of treatment. The literature is reviewed and the advantages of
      imaging together with the use of digitised data is highlighted by a case
      requiring rehabilitation with enhanced planning methods.

PMID- 11325156
TI  - Tooth discolouration and staining: a review of the literature.
AB  - OBJECTIVE: To carry out an extensive review of the literature on tooth staining
      with particular regard to some of the more recent literature on the mechanisms of
      tooth staining involving mouthrinses. DESIGN: Comprehensive review of the
      literature over four decades. CONCLUSIONS: A knowledge of the aetiology of tooth
      staining is of importance to dental surgeons in order to enable a correct
      diagnosis to be made when examining a discoloured dentition and allows the dental
      practitioner to explain to the patient the exact nature of the condition. In some
      instances, the mechanism of staining may have an effect on the outcome of
      treatment and influence the treatment options the dentist will be able to offer
      to patients.

PMID- 11325157
TI  - Clinical performance of a condensable metal-reinforced glass ionomer cement in
      primary molars.
AB  - OBJECTIVE: Aim of the present study was to evaluate the clinical suitability of
      the condensable metal-reinforced glass ionomer cement Hi-Dense in classes I and
      II cavities of primary molars. METHODS: Seventeen children received a total of
      fifty four Hi-Dense fillings (nineteen class I and thirty five class II). The
      restorations were clinically assessed at baseline, after one and after two years
      of clinical service according to modified USPHS codes and criteria. The
      restorations were replicated in each recall and representative samples were
      qualitatively analysed under a SEM. RESULTS: Over the observation period of two
      years, five restorations failed due to total retention loss, two fillings needed
      replacement because of persisting hypersensitivity, one filling was lost because
      of an unsuccessful endodontic treatment, and four restorations remained intact
      until natural exfoliation (Two year survival rate: 92% for Class I and 66% for
      Class II). The SEM analysis of surfaces and marginal areas exhibited an inferior
      adhesive performance primarily in proximal areas, whereas a negative step
      formation due to wear was frequently observed in occlusal parts. CONCLUSIONS: The
      results clearly indicate that the condensable, metal-reinforced GIC Hi-Dense
      reveals no enhanced performance and lifetime expectancy for class II restorations
      in primary molars when compared to other non-resin-modified GICs.

PMID- 11325158
TI  - Scope of the OSCE in the assessment of clinical skills in dentistry.
AB  - INTRODUCTION: The objective structured clinical examination (OSCE) is now an
      accepted tool in the assessment of clinical skills in dentistry. There are
      however no strict or limiting guidelines on the types of scenario that are used
      in the OSCE examinations and experience and experimentation will inevitably
      result in the refinement of the OSCE as a tool for assessment. AIM: The aim of
      this study was to compare and contrast different types of clinical operative
      skills scenarios in multi-station OSCE examinations. METHODOLOGY: Student
      feedback was obtained immediately after the sitting of an OSCE examination on two
      different occasions (and two different cohorts of students). The same
      questionnaire was used to elicit the responses. RESULTS: The questionnaire
      feedback was analysed qualitatively with particular regard to student perception
      of the usefulness and validity of the two different kinds of OSCE scenarios.
      CONCLUSIONS: OSCE scenarios which involve phantom heads are perceived to lack
      clinical authenticity, and are inappropriate for the assessment of certain
      clinical operative skills. While the OSCE is useful in the examination of
      diagnostic, interpretation and treatment planning skills, it has apparent
      limitations in the examination of invasive operative procedures.

PMID- 11325159
TI  - Operative mechanisms of noncontingent reinforcement at varying magnitudes and
      schedules.
AB  - In order to examine the mechanism(s) responsible for response reductions from
      noncontingent reinforcement (NCR), multiple magnitudes and densities of NCR were
      superimposed on a variable ratio (VR) 3 schedule of contingent reinforcement for
      the performance of an arbitrary manual response. Data were collected on
      responding that occurred during access to the reinforcer separately from
      responding that occurred between reinforcer access intervals (i.e.. when the
      participant did not have access to the reinforcer). Higher magnitudes and denser
      schedules of NCR produced greater reductions in responding than did lower
      magnitudes and leaner schedules. Within-session response patterns suggested that
      decrements in responding were primarily a function of the increased amount of
      reinforcer access time associated with higher magnitudes and denser schedules of
      NCR. That is, it appeared that the participant consumed reinforcers (regardless
      of whether they were delivered contingently or noncontingently) when they were
      available and responded for contingent reinforcers primarily when reinforcers
      were absent.

PMID- 11325160
TI  - Effects of different social partners on the discriminated requesting of a young
      child with autism and severe language delays.
AB  - We examined the effects of two adult social partners on the requesting repertoire
      of a young child with autism and severe language delays. We used a multiple
      schedule design (Kazdin, 1982) to evaluate the request topography that the
      participant emitted relative to each social partner's contingent differential
      reinforcement for specific requesting forms. The contingencies associated with
      each adult were reversed after the participant reached a preestablished criterion
      of discriminated responding. The participant learned to request in a
      discriminated manner in the presence of each social partner. Implications of
      these results are discussed.

PMID- 11325161
TI  - Multicomponent treatment for blood-injury-injection phobia in a young man with
      mental retardation.
AB  - Blood-Injury-Injection Phobia (BIIP) is a subtype of specific phobia,
      characterized by fear and avoidance of seeing blood, an injury, or receiving an
      injection. In the current case report, we describe the treatment of BIIP in a
      young man with mental retardation. The multicomponent treatment consisted of
      fading (graduated exposure), modeling, noncontingent and differential
      reinforcement, presession anxiolytic medication, and topical analgesic cream.

PMID- 11325162
TI  - Reducing job coach assistance for supported workers with severe multiple
      disabilities: an alternative off-site/on-site model.
AB  - Adults with severe multiple disabilities constitute a very small percentage of
      individuals in supported work. When these persons do obtain community jobs,
      considerable assistance is usually required. We evaluated an off-site/on-site
      program for reducing job coach assistance provided for three adults with severe
      multiple disabilities in a part-time community job. Following observations of the
      supported workers' job performance in a publishing company, the job support
      reduction program was implemented while the individuals received more traditional
      day services when not at work. The program involved assessing the amount and type
      of assistance provided for each step in a worker's job tasks, and then reducing
      the assistance through environmental adaptations and instruction. After
      implementation in the nonwork setting, the adaptations and instruction were
      extended to the work site. Immediate reductions occurred in the amount of
      assistance provided by job coaches for each supported worker while on the job. No
      adverse effects on productivity were observed. These results suggest that an off
      site/on-site approach to reducing work assistance represents a viable alternative
      to current supported work models. Social validity observations in 10 job sites
      highlighted the need to demonstrate ways to reduce work assistance provided for
      workers with severe multiple disabilities. Future research areas are noted,
      focusing on evaluating other models for enhancing supported work opportunities
      for people with highly significant disabilities.

PMID- 11325163
TI  - Identifying feeding problems in mentally retarded persons: development and
      reliability of the screening tool of feeding problems (STEP).
AB  - Feeding problems are extremely common among individuals with mental retardation.
      Palmer, Thompson, and Linscheid (1975) estimate that 33% of persons with mental
      retardation have severe feeding difficulties or problems. Furthermore, the
      consequences of untreated feeding problems can be severe if not fatal. Despite
      these numbers, little has been done to systematically identify these problems.
      The Screening Tool of Feeding Problems (STEP) was developed as a means to
      identify feeding problems presented by persons with mental retardation, and thus
      facilitate the process of identifying who would benefit from some type of
      behavioral or medical intervention. Items included in the STEP target feeding
      problems identified in the literature, in the areas of risk of aspiration, food
      selectivity, feeding skills deficits, food refusal and associated behavior
      problems, and nutrition related behavior problems. The current study describes
      the construction of this scale, provides psychometric data including test-retest
      and cross rater reliability, and factor analysis data.

PMID- 11325164
TI  - Simulated and community-based instruction involving persons with mild and
      moderate mental retardation.
AB  - In this study of simulated instruction and/or community training of four
      functional living tasks was compared across groups of adolescents and young
      adults with mild and moderate retardation. Forty individuals participated in the
      assessment and training activities of this study, including 20 participants with
      mild retardation and 20 individuals with moderate retardation. A mixed factorial
      design was used to evaluate differences associated with level of mental
      retardation, simulated versus community-based instruction, and assessments in
      school and community settings. Participants with mild retardation performed
      better than their counterparts with moderate retardation on the simulated tasks
      and in the community settings. Participants with mild retardation were more
      successful in generalizing from the simulated instructional experiences to the
      community settings than were their counterparts with moderate retardation.
      However, in many of the situations, community training was sufficiently powerful
      to eliminate any advantage associated with some of the participants having
      experienced prior simulated instruction. Results are discussed in relation to the
      need to more closely examine the design and delivery of functional living skills
      instruction involving individuals with different levels of mental retardation.
      Specifically, the effectiveness of instructional simulations for teaching
      functional living skills does not appear to be uniform across level of
      retardation and targeted tasks. The highest priority question no longer appears
      to be whether or not simulated versus community-based instruction is more
      efficacious. Future research might more productively focus on the quality of
      different instructional simulations in combination with community assessment
      and/or training opportunities for teaching functional living skills to persons
      who experience different levels of mental retardation.

PMID- 11325165
TI  - High dose cocaine use in Sao Paulo: a comparison of treatment and community
      samples.
AB  - This cross-sectional study investigates patterns of drug use and associated
      problems among 332 cocaine users from treatment and community samples in Sao
      Paulo, Brazil. Data were collected using a structured questionnaire and the
      Severity of Dependence Scale (SDS). The majority were regular users of high doses
      of smoked cocaine. After controlling for severity of cocaine use, users in the
      community were found to be more involved in illegal activities, more likely to
      report adverse effects of cocaine, to be involved in prostitution, and to have
      lived on the streets. Better methods are required to provide interventions to
      tackle the problems and risk behaviors of these cocaine users.

PMID- 11325166
TI  - Neuropsychological functioning in substance-dependent patients.
AB  - The present study examined neurocognitive functioning in groups of individuals
      addicted to various psychoactive substances. One hundred ten patients admitted to
      treatment for substance misuse were assessed using a semistructured clinical
      interview, the Beck Depression Inventory, the Symptom CheckList-90, the Trail
      Making A and B tests, and the Shipley Institute of Living Scale. Results revealed
      that at intake, alcohol- and benzodiazepine-addicted clients exhibited higher
      levels of cognitive impairment and psychological distress than patients dependent
      on other drugs. Regression analysis showed that the Shipley vocabulary raw score
      was a significant predictor of length of stay in treatment.

PMID- 11325167
TI  - A self-administered instrument for assessing therapeutic approaches of drug-user
      treatment counselors.
AB  - In this article we describe the development and psychometric properties of a self
      administered instrument for assessing drug-user treatment counselors' therapeutic
      approaches such as psychodynamic or interpersonal, cognitive-behavioral, family
      systems or dynamics, 12-step, and case management. We generated an initial pool
      of items corresponding to these five approaches and modified them based on expert
      ratings. We developed three sets of items. The first concerned the beliefs
      underlying each therapeutic approach. The second and third concerned the
      practices of each applicable approach within individual and group counseling,
      respectively. With the exception of case management, an approach that originated
      within social work and which is only applicable to individual counseling, the
      other four approaches are applicable, at least theoretically, to both individual
      and group counseling. Additionally, we included items that describe techniques
      used exclusively with groups (i.e., group techniques). Finally, we included some
      items that are not associated with any of the traditional approaches but which
      reflect the practical approach that drug-user treatment programs often take to
      both individual and group counseling (i.e., practical counseling). The initial
      instrument consisted of 17 subscales with a total of 76 items. This instrument
      was administered to 226 counselors from 45 drug-user treatment programs in Los
      Angeles County. Based on this data, we further refined these scales using
      confirmatory factor analysis to ensure both construct validity and discriminant
      validity. The final instrument consisted of 14 subscales with a total of 48
      items.

PMID- 11325168
TI  - Sober living houses: potential roles in substance abuse services and suggestions
      for research.
AB  - 'Sober living houses' are alcohol- and drug-free residences for individuals
      attempting to establish or maintain sobriety. They offer no formal treatment
      services but do provide social support and an abstinent living environment.
      'Sober living houses' have been used as aftercare placements for clients
      completing residential treatment, places for clients to live while attending
      outpatient treatment, or as stand-alone approaches for substance misuse problems.
      This article identifies areas of research needing attention and suggests that
      'sober living houses' have the potential to play a stronger role in the continuum
      of substance misuse services.

PMID- 11325169
TI  - Cross-cultural evaluation of two drinking assessment instruments: alcohol
      timeline followback and inventory of drinking situations.
AB  - This article describes the psychometric characteristics of two major assessment
      instruments used in a World Health Organization (WHO) clinical trial: (a) Alcohol
      Timeline Followback (TLFB, which assesses daily drinking patterns), and (b)
      Inventory of Drinking Situations (IDS, which assesses antecedents to "heavy"
      drinking). Clients (N = 308) were outpatient alcohol abusers from four countries
      (Australia, Canada, Mexico, and Sweden). Generally, the Alcohol TLFB and IDS were
      shown to be reliable and valid with outpatient alcohol abusers in four countries,
      and in three languages. These results suggest that the Alcohol TLFB and the IDS
      can be used in clinical and research settings with Swedish-, Spanish-, and
      English-speaking alcohol abusers.

PMID- 11325170
TI  - "If it burns going down... ": how focus groups can shape fetal alcohol syndrome
      (FAS) prevention.
AB  - Despite public health campaigns and clinical interventions that encourage women
      to abstain from alcohol during pregnancy, some women continue to drink while
      pregnant. To provide a more in-depth understanding of how at-risk women regard-
      and emotionally react to--warnings about drinking alcohol during pregnancy, we
      conducted focus groups in 1997 with 11 pregnant and recent postpartum Native
      American and African American women in Los Angeles, California. The main
      objective of these groups was to uncover relevant aspects of women's beliefs and
      opinions about drinking during pregnancy that may not have been elicited by other
      research instruments. Results would then be used to shape a large survey of
      pregnant at-risk women. Analysis of the transcripts revealed three emergent
      themes, which had the greatest impact on our subsequent survey. These were
      women's exposure to and perceived believability of messages, their perception of
      risk associated with drinking, and the barriers to cutting down on alcohol
      consumption during pregnancy. Questions added to our survey instrument because of
      these findings included whether women think that some alcohol beverages are safer
      to drink than others; how they value cutting back alcohol use; their views on the
      irreversibility of fetal alcohol syndrome; and what pressures they feel from
      peers and family to drink during pregnancy. Given the small sample size
      associated with focus groups, these results cannot be generalized to larger
      populations; however, these women's words revealed important underlying issues
      and barriers that should be considered in studying and intervening with larger
      representative samples.

PMID- 11325171
TI  - "You become really close... you talk about the silly things you did, and we
      laugh": the role of binge drinking in female secondary students' lives.
AB  - In Australia, negative attitudes regarding young women's drinking have eased,
      drinking is on the increase, and there are heightened concerns about 'heavy' or
      'binge' drinking. In a climate where underage drinking is frequently considered
      undesirable, campaigns aimed at reducing 'heavy' alcohol use have failed. This
      article takes as its departure point the notion that alcohol plays a meaningful
      role in social lives and relationships. It is through the use of narrative that
      these young women make sense of their drinking, which is still stigmatized. Any
      harm encountered along the way tends to be filtered through the 'good story,'
      brimming with tales of fun, adventure, bonding, sex, gender transgressions, and
      relationships. Nevertheless, these women implemented their own practical harm
      minimization strategies, and it is here that professionals can gain a foothold
      and assist young people and help them to drink more safely.

PMID- 11325172
TI  - Drug use prevention for the high sensation seeker: the role of alternative
      activities.
AB  - Research demonstrating links between sensation-seeking and drug use, and
      sensation-seeking and participation in leisure activities suggests designing
      substance misuse prevention projects that encourage substituting alternative
      activities for drug use. The current study uses factor analysis and discriminant
      analysis to provide comprehensive information on the kinds of activities high
      sensation seekers participate in. Factor analysis of activity participation
      indicates an eight factor solution. Discriminant analysis of factor scores
      indicates that high-sensation seekers can be discriminated from low-sensation
      seekers on the basis of two factors, active-adventure and conflict-combat.
      Implications for prevention program design are discussed.

PMID- 11325173
TI  - Drinking patterns and beverage preferences of liver cirrhosis patients in Mexico.
AB  - The purpose of this study was to investigate the pattern of alcoholism in a
      special group of alcoholics (alcoholic cirrhotics) in a hospital-based population
      in west central Mexico and assess the role of regional spirits such as tequila. A
      complete alcohol drinking history and a structured questionnaire directed at
      investigating the pattern of alcohol consumption was applied to 124 adult
      patients with chronic liver disease caused by alcohol during January 1995 to
      January 1996. The mean age of onset was 27 +/- 3 years in women and 18 +/- 0.5
      years in men. The mean alcohol intake per week was 749 +/- 192 g for women and
      1113 +/- 151 g for men. On average, patients consumed alcohol for a mean of 24.5
      years. The overall patient drinking preference was for tequila followed by 96
      degree Gay Lusac (G.L.), alcohol, and beer. In a subset of 70 patients three
      phases of alcoholism could be identified (prealcoholic, critical, and chronic).
      Each phase had a mean duration of at least 11 years. Beer was the dominant
      beverage in the prealcoholic phase while tequila was consumed more often in the
      other phases. In the critical phase of alcoholism an average of 337 g of alcohol
      were consumed per week and in the chronic phase 1765 g/week. Tequila was the
      overall preferred beverage in this group of alcoholics. Other beverages included
      beer and straight alcohol with a clear trend from less to higher concentration of
      alcohol throughout the drinking history. Subtle gender differences in the
      patterns of alcoholism may be suspected. In this group of patients the role of
      tequila drinking is highlighted.

PMID- 11325174
TI  - The effect of early postnatal treatment with a gonadotropin-releasing hormone
      agonist on the developmental profiles of testicular steroid hormones in the
      intact male pig.
AB  - Three studies examined the effects of early postnatal treatment with a GnRH
      agonist on plasma concentrations of testosterone, dehydroepian-drosterone
      sulfate, 16-androstene steroids in fat and salivary glands, androstenone in fat
      and plasma, and testicular development of intact male pigs. The first study
      involved 45 7-d-old pigs assigned to three treatment groups: 1) boars
      administered 100 microg/kg of Lupron depot, 2) boars administered 200 microg/kg
      of Lupron depot, and 3) control boars receiving a saline carrier. The second
      study involved 20 7-d-old pigs assigned to two treatments: daily injection of 200
      microL of 0.5 mg/mL Lupron from d 7 to 35 and controls treated with saline. The
      third study involved a total of 100 animals assigned to 10 groups of 10 based on
      their age at slaughter. These groups were subdivided into one of two treatments:
      1) boars injected with 200 microL of 0.5 mg/mL of Lupron from d 3 to 35 and 2)
      control boars injected with saline. Testicular steroid hormone concentrations in
      plasma decreased (P < 0.01) within 7 d of GnRH agonist treatment. Following
      cessation of treatment, steroid levels increased to control levels and remained
      constant until the final rise at 5 mo. Plasma testosterone levels in the 100
      microg/kg depot treatment group were higher (P < 0.05) than that of the 200
      microg/kg and control group at 164 d of age. There were no differences between
      treatments (P > 0.05) in testicular steroid hormone levels at the end of study 2
      or 3. There were no differences (P > 0.05) in concentrations of 16-androstene
      steroids in salivary glands between any of the treatment groups at market weight
      in studies 1 and 2. Fat androstenone levels measured in the third study ranged
      between 0.6 microg/g and 4.2 microg/g at 7 to 28 d of age. Treatment with GnRH
      agonist decreased plasma steroid levels and testicular development; however, by d
      60 testicular size and weight were at control levels and remained similar until
      180 d of age. The results of these studies indicate that daily administration of
      a GnRH agonist significantly decreased testicular development and steroidogenesis
      only during treatment, but testis growth and steroidogenesis had returned to
      control levels by 60 d of age in male pigs. Suppression of the early postnatal
      rise in testicular steroid hormones did not affect growth performance or steroid
      hormone levels at 5 to 6 mo of age.

PMID- 11325175
TI  - Tasco-Forage: I. Influence of a seaweed extract on antioxidant activity in tall
      fescue and in ruminants.
AB  - Seaweed (Ascophyllum nodosum) is a known source of plant growth regulators, and
      application to turfgrasses has increased activity of the antioxidant superoxide
      dismutase (SOD) and specific vitamin precursors. Increased antioxidant activity
      in both plants and animals diminishes oxidative stress. Two pasture experiments
      investigated effects of Tasco-Forage (a proprietary seaweed-based product)
      applied to tall fescue (Festuca arundinacea) on antioxidant activity in plants
      and in ruminants that grazed the forage. In Exp. 1, fescue was 70 to 100%
      infected with the endophyte fungus Neotyphodium coenophialum ([Morgan-Jones and
      Gams] Glenn, Bacon, and Hanlin). Twenty-four wether lambs (initial BW 41 kg; SD =
      5) grazed fescue treated with 0, 1.7, or 3.4 kg Tasco/ha applied in April and
      July, 1994, with four replications per treatment. Grazing occurred for 26 d
      beginning April 21 and for 22 d beginning July 19. In July, there was a linear
      increase in daily gains (P < 0.05), and serum vitamin A (P < 0.13) and whole
      blood Se (P < 0.10) tended to increase in lambs grazing Tasco-treated fescue. In
      Exp. 2,48 Angus and Angus x Hereford steers (initial BW 245 kg; SD = 20) grazed
      infected or uninfected tall fescue in Virginia that was treated (3.4 kg/ ha) or
      untreated with Tasco in April and July, 1995. Steers that grazed infected tall
      fescue had lower (P < 0.02) serum vitamin A and E and tended (P < 0.07) to have
      lower whole-blood Se in September compared with steers that grazed uninfected
      tall fescue. Tasco decreased (P < 0.06) serum vitamin E but tended to increase
      whole-blood Se (P < 0.10) in September and serum vitamin A in July (P < 0.12).
      During 1996 and 1997, the experiment was repeated in Virginia with Angus steers
      and was replicated at Prairie, MS, where 1/4 Brahman x 3/4 Angus steers were
      used. Forty-eight steers were included at each location in each year (n = 192
      total steers for 1996 and 1997). Steers that grazed infected tall fescue in
      Mississippi had lower (P < 0.05) serum vitamin E by the end of the grazing
      season. At both locations Tasco increased (P < 0.05) activity of superoxide
      dismutase in both infected and uninfected fescue. The endophyte in tall fescue
      seemed to decrease antioxidant activity in grazing steers, whereas Tasco seemed
      to increase antioxidant activity in both the forage and the grazing ruminant.
      Tasco may provide opportunities to reduce oxidative stress in plants and animals.

PMID- 11325176
TI  - Tasco-Forage: II. Monocyte immune cell response and performance of beef steers
      grazing tall fescue treated with a seaweed extract.
AB  - Effects of applying Tasco-Forage, an Ascophyllum nodosum seaweed-based product
      prepared by a proprietary process, to endophyte (Neotyphodium coenophialum
      [Morgan-Jones and Gams] Glenn, Bacon, and Hanlin)-infected and endophyte-free
      tall fescue (Festuca arundinacea Schreb.) were studied in each of 3 yr (1995,
      1996, and 1997) in Virginia and in 1996 and 1997 in Mississippi. There were 48
      steers at each location in each year (n = 240) in a 2 x 2 x 2 factorial
      arrangement with two replications at each location. Steers in Virginia were Angus
      and Angus x Hereford with initial weights of 245 kg (SD = 20), 234 kg (SD = 9),
      and 265 kg (SD = 5) in yr 1, 2, and 3, respectively. Steers in Mississippi were
      3/4 Angus and 1/4 Brahman and weighed 230 kg (SD = 8) and 250 kg (SD = 2) in yr 2
      and 3, respectively. Tasco (3.4 kg/ha) was dissolved in water and applied to
      pastures in April before grazing was begun and again in July at the same rate.
      The grazing period was from mid-April to late September or mid-October. Total
      gains were higher (P < 0.05) for steers grazing uninfected than for those grazing
      endophyte-infected tall fescue. Rectal temperatures were increased (P < 0.05) due
      to endophyte infection at both locations; Tasco application decreased temperature
      of steers grazing infected fescue in Virginia (interaction, P < 0.07) but
      increased temperatures of steers grazing infected fescue in Mississippi
      (interaction, P < 0.05). Presence of the endophyte resulted in rough hair coats
      and loss of hair color, but the effect was partially offset (P < 0.05) by Tasco
      application in Virginia in 1995. Both monocyte phagocytic activity (all years and
      locations) and major histocompatibility complex class II expression (1995 only)
      were decreased (P < 0.05) in steers due to endophyte infection, but this effect
      was reversed (P < 0.05) by application of Tasco to pastures. Application of the
      extract from A. nodosum seems to have use in alleviating adverse effects of
      endophyte on immune function and may improve hair coat condition in cattle
      grazing infected fescue, but effects on rectal temperature varied due to
      location.

PMID- 11325177
TI  - Tasco-Forage: III. Influence of a seaweed extract on performance, monocyte immune
      cell response, and carcass characteristics in feedlot-finished steers.
AB  - Tall fescue (Festuca arundinacea Schreb.) infected with the endophyte
      Neotyphodium coenophialum ([Morgan-Jones and Gams] Glenn, Bacon, and Hanlin)
      causes fescue toxicosis in cattle grazing the forage, but effects of the
      endophyte were considered to be abated soon after removal of the animals from
      pastures. Tasco-Forage, a proprietary extract from the brown seaweed Ascophyllum
      nodosum, is a known source of cytokinins and has increased antioxidant activity
      in both plants and the animals that graze the forage. Tasco was applied at 0 and
      3.4 kg/ha to infected and uninfected tall fescue pastures in Virginia and
      Mississippi. Forty-eight steers grazed the pastures at each location during each
      of 2 yr (n = 192) before being transported to Texas for feedlot finishing. On
      arrival at the feedlot, steers from Tasco-treated pastures had higher (P < 0.01)
      monocyte phagocytic activity and tended (P < 0.07) to have higher major
      histocompatibility complex class II expression than steers that grazed the
      untreated pastures. A depression (P < 0.05) in monocyte immune cell function due
      to grazing infected fescue was detected throughout the feedlot finishing period
      but was reversed by Tasco. Rectal temperatures were elevated (P < 0.07) in steers
      that had grazed the infected tall fescue when they arrived in Texas, but by d 14
      no difference was detected. However, by d 28 the temperature effects of infected
      tall fescue were reversed. Steers that had grazed infected fescue had lower (P <
      0.01) rectal temperatures on d 112 of the feedlot period, demonstrating a much
      longer-lasting effect of the endophyte on thermoregulatory mechanisms than
      previously thought. Steers that had grazed Tasco-treated pastures had higher (P <
      0.01) rectal temperatures on d 56 than steers that had grazed untreated fescue.
      Steers that had grazed the Tasco-treated pastures had higher marbling scores (P <
      0.05) regardless of the endophyte, but no effect of Tasco or endophyte on gain
      was measured. Our data suggest that Tasco application to tall fescue pastures
      alleviated some of the negative effects of tall fescue toxicity.

PMID- 11325178
TI  - Effects of supplement type on animal performance, forage intake, digestion, and
      ruminal measurements of growing beef cattle.
AB  - Two experiments were conducted to determine the effects of supplement type on the
      rate of gain by heifers grazing bermudagrass and on the intake, apparent total
      tract OM digestibility, ruminal fermentation, digesta kinetics, in situ DM
      digestibility, and forage protein degradation by steers fed prairie hay. In Exp.
      1, 45 heifers (284+/-24 kg) grazed a bermudagrass pasture for 91 d in the late
      summer to determine the effects of no supplement (CON), or one of four
      individually fed monensin-containing (150 mg/[heifer x d]) supplements (MINCS;
      0.1 kg of mineral mix with 0.2 kg [DM] of cottonseed hulls as a carrier/[heifer x
      d]), a pelleted protein supplement (PROT; 1 kg of DM, 242 g of degradable intake
      protein [DIP]/[heifer x d]), or high-fiber (HF) and high-grain (HG) (2 kg of DM,
      243 and 257 g of DIP, respectively/[heifer x d]) pelleted energy supplements. In
      Exp. 2, four ruminally cannulated steers (311+/-22 kg) with ad libitum access to
      low-quality (4% DIP, 73% NDF, 40% ADF) prairie hay were individually fed monensin
      containing (200 mg/[steer x d]) treatments consisting of 1) mineral mix + corn
      (MINCR; 0.1 kg of mineral and 0.4 kg of cracked corn [DM] as a carrier, 19 g of
      DIP/[steer x d]), 2) PROT (1.4 kg of DM, 335 g of DIP/[steer x d]), 3) HF, or 4)
      HG (2.9 kg of DM, 340 and 360 g of DIP, respectively/[steer x d]) in a 4 x 4
      Latin square with 14-d adaptation and 6-d sampling periods. In Exp. 1, the HF-,
      HG-, and PROT-supplemented heifers had greater (P < 0.01) rates of gain than CON
      heifers, and the HF- and HG-supplemented heifers tended (P < 0.11) to gain more
      weight than those fed PROT. In Exp. 2, steers fed PROT consumed more (P < 0.05)
      hay OM than HF and HG, or MINCR. Total OM intake was greater (P < 0.01) by
      supplemented steers than MINCR-fed cattle. Hay OM digestibility was not affected
      (P = 0.19) by treatment, but total diet OM digestibility was greater (P < 0.01)
      for HF- and HG- than for MINCR- or PROT-fed steers. The rate of in situ DM
      digestibility was greater (P < 0.01) for HF, HG, and PROT than for MINCR. Results
      from these studies indicate that feeding milo- vs fiber-based energy supplements
      formulated to provide adequate DIP did not result in different forage intake, OM
      digestibility, or in situ DM digestibility, whereas both increased ADG in heifers
      consuming low-quality forages compared with unsupplemented or mineral- or protein
      supplemented cattle. An adequate DIP:TDN balance decreased the negative
      associative effects often observed when large quantities of high-starch
      supplements are fed with low-quality hay.

PMID- 11325179
TI  - The effect of season and monensin sodium on the digestive characteristics of
      autumn and spring pasture fed to sheep.
AB  - The effects of season of growth and monensin treatment on ruminal digestion of
      fresh-cut autumn and spring pasture were measured in a single group of ruminally
      fistulated castrated male sheep, housed indoors in metabolism crates. Responses
      were assessed in terms of ruminal volatile fatty acid molar proportions, ammonia
      concentration, pH, apparent digestibility of the pasture, and nitrogen balance of
      the animals. Blood plasma concentrations of insulin, glucose, beta
      hydroxybutyrate, urea, and NEFA were also evaluated. Autumn pasture contained
      significantly lower proportions of water-soluble carbohydrate (P < 0.05),
      cellulose (P < 0.05), and lignin (P < 0.05) and increased pectin (P < 0.05),
      hemicellulose (P < 0.05), and crude protein (P < 0.10) concentrations when
      compared with spring pasture. Voluntary DMI by sheep of autumn pasture was lower
      (P < 0.01) than that of spring pasture and was significantly (P < 0.05) reduced
      by monensin treatment. Monensin treatment significantly decreased the ruminal
      molar proportions of acetic acid (P < 0.10) and butyric acid (P < 0.001) and
      increased the molar proportions of propionic acid (P < 0.001) and minor VFA (P <
      0.01). Nitrogen retention of the sheep was significantly (P < 0.05) reduced by
      monensin treatment. Plasma glucose levels were increased (P < 0.10) by monensin
      treatment during the fourth 5-d collection period in both seasons. Chemical
      analysis suggested that the composition of autumn pasture was different from that
      of spring pasture and that this was manifested in vivo by increased DMI and
      digestibility of spring vs autumn pasture. Ruminal fermentation of autumn pasture
      also had an increased acetate-to-propionate ratio compared with spring pasture.
      Monensin treatment acted consistently across seasons by increasing the proportion
      of propionate and decreasing the proportion of acetate in ruminal fluid.

PMID- 11325180
TI  - Evaluation of titanium dioxide as a digestibility marker for cattle.
AB  - Three studies were conducted to evaluate titanium dioxide (TiO2) as a
      digestibility marker for cattle. In Exp. 1, eight steers consumed prairie hay ad
      libitum with or without dietary supplements. Fecal recovery of TiO2 averaged 93%
      and was not affected (P = 0.47) by supplement. Digestibilities calculated with
      reference to TiO2 were not different (P = 0.15) from those based on total fecal
      collections. In Exp. 2, two steers were limit-fed corn-based diets. Fecal
      recovery of TiO2 averaged 95% and that of chromic oxide (Cr2O3) averaged 113%.
      Digestibilities calculated with reference to TiO2 were underestimated (P < 0.01)
      by 1.1 percentage units relative to those based on total fecal collections, and
      those calculated with reference to Cr2O3 were overestimated (P < 0.01) by 2.0
      percentage units. In Exp. 3, eight steers in a replicated 4 x 4 Latin square
      consumed corn-based diets ad libitum. Fecal recovery of TiO2 averaged 90%,
      whereas that of Cr2O3 averaged 98%. Digestibilities calculated with reference to
      TiO2 were underestimated (P < 0.01) by 1.6 to 4.3 percentage units, whereas those
      calculated with reference to Cr2O3 were not different (P = 0.31) from those based
      on total fecal collections. Future research is warranted to determine the
      usefulness of TiO2 in measuring digestibility in cattle.

PMID- 11325181
TI  - Effect of prepubertal feeding regimen on reproductive development and performance
      of gilts through the first pregnancy.
AB  - Development of gilts that conceive early and continue to produce offspring is an
      objective of swine production. We investigated different patterns of growth on
      reproductive development and performance of gilts through the first farrowing. At
      13 wk of age and 43 kg BW, 286 white crossbred gilts were penned individually and
      assigned to treatments: Ad lib, ad libitum intake from 13 to 25 wk of age;
      Control, ad libitum intake from 13 wk of age until 100 kg BW and then 90% of ad
      libitum intake until 25 wk of age; and Restricted, 74% of ad libitum intake from
      13 wk to 25 wk of age. Feed was formulated to restrict energy intake. The study
      was replicated in three seasons. At 25 wk of age, gilts were moved by treatment
      to group pens, fed for ad libitum consumption, and estrus detection was
      initiated. Gilts were inseminated at first estrus, and those recycling were
      remated. Postmating gilts were fed 1.5x maintenance until 105 to 110 d of
      pregnancy. Gilts were moved either to the farrowing facility or the abattoir at
      105 to 110 d of pregnancy. Those taken to the abattoir were slaughtered and
      number, weight, and condition of the fetuses were recorded. Gilts moved to the
      farrowing facility were allowed to farrow, and number, weight, and condition of
      the piglets were recorded. Daily feed intake during breeding was 3.4 kg/d by
      Restricted gilts, 2.9 by Control gilts, and 2.7 kg/d by Ad lib gilts. Increased
      feed intake by Restricted gilts during breeding resulted in compensatory gains
      that overcame the reduced reproductive performance that resulted from the reduced
      BW and backfat these gilts carried at the start of breeding. Days to first estrus
      and pregnancy were not influenced by development period treatment (P < 0.13).
      Percentage of Ad lib, Control, and Restricted gilts that successfully completed
      their pregnancies were 61, 74, and 66, respectively (P > 0.19). Total feed fed
      from 13 wk of age to end of the first pregnancy per gilt assigned did not differ
      among Ad lib (506 kg) and Control (498 kg) gilts but was less (P < 0.01) in
      Restricted gilts (451 kg). Number of piglets born per gilt assigned (P > 0.09)
      and piglets produced per kilogram of feed fed from 13 wk of age to term (P >
      0.29) were 6.47 and 0.0134 in Ad lib gilts, 7.26 and 0.0150 in Control gilts, and
      6.38 and 0.0149 in Restricted gilts, respectively. Moderate feed restriction, 74%
      of ad libitum intake, reduced feed consumed from 13 wk of age to end of the first
      pregnancy with no significant impact on efficiency of piglet production.

PMID- 11325183
TI  - Effect of group size and feeder type on growth performance and feeding patterns
      in growing pigs.
AB  - The effects of four group sizes (2, 4, 8, and 12 pigs per pen) and two single
      space feeder types (conventional and electronic feed intake recording equipment
      [FIRE]) on feed intake, growth performance, and feeding patterns were determined
      in growing pigs over a 4-wk period. A total of 416 hybrid pigs (barrows and
      gilts) were grown from 26.5 (SD = 1.6) to 47.8 (SD = 2.7) kg BW and given ad
      libitum access to a corn-soybean meal-based diet (17.4% CP; 0.9% lysine; 3,298
      kcal ME/kg). The floor space allowance was 0.9 m2/pig for all treatments. Pigs
      using the electronic feeders had similar growth rates but lower feed intakes (P <
      0.01) and higher gain:feed ratios (P < 0.01) compared to those using the
      conventional feeders. Barrows compared to gilts had higher growth rates (P <
      0.05), numerically higher (P > 0.05) ADFI, and similar feed efficiency and
      feeding pattern. Feed intakes and growth rates were lowest (P < 0.05) for groups
      of 12 pigs but gain:feed ratio was not affected by group size. Daily feeder
      occupation time per pig was lower (P < 0.01) for groups of 12 than for groups of
      2 or 4 pigs, and feed consumption rate was higher (P < 0.01) for groups of 12
      than for groups of 4 pigs. The proportion of time spent eating was lower (P <
      0.01) and the proportion of time spent standing was higher (P < 0.01) for pigs in
      groups of 12 compared to groups of 2. Correlations between ADG and ADFI and feed
      intake per visit were 0.29 and 0.30, respectively (P < 0.01), between ADG and
      ADFI and feed consumption rate were 0.27 and 0.31, respectively (P < 0.01), and
      between ADFI and feeder occupation time per day were 0.33 (P < 0.01). This study
      suggests that, in growing pigs given access to a single feeder, changes in
      feeding behavior with increasing group size were not sufficient to maintain feed
      intake and growth rate.

PMID- 11325182
TI  - Administration of p.g. 600 to sows at weaning and the time of ovulation as
      determined by transrectal ultrasound.
AB  - This study determined whether the interval from estrus to ovulation was altered
      by giving P.G. 600 to sows at weaning. Mixed-parity sows received P.G. 600 i.m.
      (n = 72) or no treatment (n = 65) at weaning (d 0). Beginning on d 0, sows were
      observed for estrus twice daily. At the onset of estrus and thereafter,
      ultrasound was performed twice daily to determine the average size of the largest
      follicles and time of ovulation. Weaning age (20.1+/-0.4 d) did not differ (P >
      0.10) between treatments. More P.G. 600 sows expressed estrus within 8 d (P <
      0.01) than controls (94.4% vs 78.4%, respectively). Parity was associated with
      expression of estrus (P < 0.02), with 78% of first-parity and 93% of later-parity
      sows exhibiting estrus. However, no treatment x parity effect was observed (P >
      0.10). The interval from weaning to estrus was reduced (P < 0.0001) by P.G. 600
      compared with controls (3.8+/-0.1 d vs 4.9+/-0.1 d). Follicle size at estrus was
      not affected by treatment (P > 0.10). The percentage of sows that ovulated did
      not differ (P > 0.10) for P.G. 600 and control sows (90.3% vs 81.5%,
      respectively). Time of ovulation after estrus was not affected by treatment and
      averaged 44.8 h. However, univariate analysis indicated that the interval from
      weaning to estrus influenced the interval from estrus to ovulation (r = 0.43, P <
      0.0001). Further, multivariate analysis showed an effect of treatment on the
      intervals from weaning to estrus, weaning to ovulation (P < 0.0001), and estrus
      to ovulation (P < 0.04). Within 4 d after weaning, 81% of the P.G. 600 sows had
      expressed estrus compared with 33% of controls. However, this trend reversed for
      ovulation, with only 35% of P.G. 600 sows ovulating by 36 h after estrus compared
      with 40% of controls. The estrus-to-ovulation interval was also longer for
      control and P.G. 600 sows expressing estrus < or = 3 d of weaning (45 h and 58 h,
      respectively) than for sows expressing estrus after 5 d (39 h and 32 h,
      respectively). Farrowing rate and litter size were not influenced by treatment.
      However, the interval from last insemination to ovulation (P < 0.02) indicated
      that more sows farrowed (80%) when the last insemination occurred at < or = 23 to
      > or = 0 h before ovulation compared with insemination > or = 24 h before
      ovulation (55%). In summary, P.G. 600 enhanced the expression of estrus and
      ovulation in weaned sows but, breeding protocols may need to be optimized for
      time of ovulation based on the interval from weaning to estrus.

PMID- 11325184
TI  - Usefulness of subjective ovine milk scores: I. Associations with range ewe
      characteristics and lamb production.
AB  - Range ewes are commonly evaluated for milking ability by producers to determine
      the ewe's ability to rear lamb(s). The U.S. Sheep Experiment Station has
      subjectively scored (low, average, high) a ewe's milking ability within 24 h of
      lambing for many years. The relationship of subjective milk scores with lamb
      production was investigated using lambing records of Columbia (n = 1,731),
      Polypay (n = 1,129), Rambouillet (n = 1,704), and Targhee (n = 1,638) ewes. The
      incidence of high milk scores increased from less than 10% at first parity to 29
      to 40% at second and greater parities. At maturity, Columbia ewes (38%) had the
      highest percentage of high milk scores. A positive association existed between
      ewe BW and her milk score at third and later parities. Ewes with high milk scores
      gave birth to heavier lambs (P < 0.05), whereas ewes with low milk scores were
      associated with lighter (P < 0.05) lambs at birth. Ewes with low milk scores
      weaned less (P < 0.05) total weight than ewes with better milk scores across all
      age groups for all breeds. Lighter weaned litter weights from ewes with low milk
      scores were linked to lighter birth weights and fewer weaned lambs. Differences
      for litter weight weaned between ewes with average and high milk scores were
      generally observed at 2 and 3 yr of age, when litter weights were heavier among
      ewes with high milk scores (P < 0.05) for all breeds. Between the ages of 1 and 3
      yr, Columbia, Polypay, Rambouillet, and Targhee ewes with an average milk score
      weaned heavier (P < 0.05) litters (average differences of 10, 9, 13, and 12%,
      respectively) than ewes with low milk scores. For all breeds at all ages,
      individual lamb weaning weights were heavier (P < 0.05) when they were reared by
      ewes with high milk scores compared to lambs reared by ewes with low milk scores.
      Results suggest that milk score is an economically important trait in these four
      breeds and should be considered in management and breeding objectives; at a
      minimum, the incidence of low milk scores should be kept as small as possible.

PMID- 11325185
TI  - Production performance of beef cows raised on three different nutritionally
      controlled heifer development programs.
AB  - The objective of this study was to determine primiparous heifer performance
      following three different heifer development strategies that were the result of
      timed nutrient limitation. Two hundred eighty-two spring-born MARC III heifers
      were weaned at 203+/-1 d of age and 205+/-1 kg BW. The experiment was conducted
      on two calf crops with 120 heifers born in 1996 and 162 heifers born in 1997.
      Treatments consisted of different quantities of the same diet being offered for a
      205-d period. Heifers in the HIGH treatment were offered 263 kcal ME/(BWkg)0.75
      daily. Heifers in the MEDIUM treatment were offered 238 kcal ME/(BWkg)0.75 daily.
      Heifers in the LOW-HIGH treatment were offered 157 kcal ME/(BWkg)0.75 daily the
      first 83 d and 277 kcal ME/(BWkg)0.75 daily for the remainder of the 205 d.
      Treatments differed in total ME intake (P < 0.001); heifers on the HIGH treatment
      consumed 3,072+/-59 Mcal/heifer, those on the MEDIUM treatment consumed 2,854+/
      21 Mcal/heifer, and those on the LOW-HIGH treatment consumed 2,652+/-19 Mcal/
      heifer. At the beginning of breeding, heifers on the HIGH treatment were taller
      at the hips (P = 0.01) and weighed more (P < 0.001) than heifers in the other two
      treatments. The percentage of heifers that calved expressed as a fraction of the
      cows exposed did not differ among treatments (89.7%; P = 0.83). The age of heifer
      at parturition (P = 0.74) and the time from first bull exposure to calving (P =
      0.38) did not differ among treatments. Birth weight of calves (P = 0.80) and the
      calves' weaning weight (P = 0.60) did not differ among the treatments. Calf
      survival rate on the LOW-HIGH treatment (73%) was lower than that on the moderate
      treatment (89%; P = 0.007) but did not differ from that on the HIGH treatment
      (81%; P = 0.26). The second-calf pregnancy rate (92.8%) for cows with a nursing
      calf at the start of breeding did not differ between treatments (P = 0.83). These
      findings suggest that as long as heifers are growing and meet a minimal BW before
      mating, patterns of growth may be altered in the post-weaning period without a
      decrease in the ability of the heifer to conceive or a decrease in calf growth
      potential. However, limit-feeding heifers may decrease first-calf survival. These
      alterations in postweaning gain through monitoring the amount of feed offered can
      be used to optimize feed resources.

PMID- 11325187
TI  - Approximation of reliabilities for multiple-trait model with maternal effects.
AB  - Reliabilities for a multiple-trait maternal model were obtained by combining
      reliabilities obtained from single-trait models. Single-trait reliabilities were
      obtained using an approximation that supported models with additive and permanent
      environmental effects. For the direct effect, the maternal and permanent
      environmental variances were assigned to the residual. For the maternal effect,
      variance of the direct effect was assigned to the residual. Data included 10,550
      birth weight, 11,819 weaning weight, and 3,617 postweaning gain records of
      Senepol cattle. Reliabilities were obtained by generalized inversion and by using
      single-trait and multiple-trait approximation methods. Some reliabilities
      obtained by inversion were negative because inbreeding was ignored in calculating
      the inverse of the relationship matrix. The multiple-trait approximation method
      reduced the bias of approximation when compared with the single-trait method. The
      correlations between reliabilities obtained by inversion and by multiple-trait
      procedures for the direct effect were 0.85 for birth weight, 0.94 for weaning
      weight, and 0.96 for postweaning gain. Correlations for maternal effects for
      birth weight and weaning weight were 0.96 to 0.98 for both approximations.
      Further improvements can be achieved by refining the single-trait procedures.

PMID- 11325186
TI  - Influence of protein supplementation and implant status on alleviating fescue
      toxicosis.
AB  - Heat stress is a major problem in transporting stocker calves with symptoms of
      fescue toxicosis. Removing calves from tall fescue pastures and offering diets
      devoid of endophyte-infected tall fescue could reduce the severity of toxicosis
      and precondition calves for transport to the feedlot. In the present experiment,
      a pasture phase was used to condition yearling steers to grazing tall fescue and
      induce symptoms of fescue toxicosis, and a pen phase followed to determine
      effects of implanting at the start of grazing and protein supplementation (hay
      only vs hay plus supplement) on short-term changes in rectal temperature and
      serum prolactin concentration. Neither implant status nor protein supplementation
      affected (P > 0.10) white blood cell count or rectal temperature. White blood
      cell counts at the conclusion of the pasture phase averaged 8,778 cells/microL
      and were within a range indicating no immunological response. Changes in rectal
      temperature and serum prolactin concentration during the pen phase were not
      influenced (P > 0.10) by implanting or supplementation. Initial rectal
      temperatures for the pen phase were high (39.9 degrees C) but declined linearly
      (P < 0.001) over the first 106 h and were below a normal temperature (39.2
      degrees C) by 82 h following removal from tall fescue pastures. Serum prolactin
      gradually increased (P < 0.001) to a peak by 82 h and stabilized thereafter.
      Results indicate that neither supplemental protein nor an estrogenic implant
      influenced recovery indices of fescue toxicosis, whereas removing calves from
      tall fescue pastures and excluding dietary tall fescue for 3 to 4 d may alleviate
      symptoms of fescue toxicosis.

PMID- 11325188
TI  - Predicting rates of inbreeding for livestock improvement schemes.
AB  - This article presents a deterministic method to predict rates of inbreeding
      (deltaF) for typical livestock improvement schemes. The method is based on a
      recently developed general theory to predict rates of inbreeding, which uses the
      concept of long-term genetic contributions. A typical livestock breeding
      population was modeled, with overlapping generations, BLUP selection, and progeny
      testing of male selection candidates. Two types of selection were practiced:
      animals were either selected by truncation on estimated breeding values (EBV)
      across age classes, or the number of parents selected from each age class was set
      to a fixed value and truncation selection was practiced within age classes.
      Bulmer's equilibrium genetic parameters were obtained by iterating on a pseudo
      BLUP selection index and deltaF was predicted for the equilibrium situation.
      Predictions were substantially more accurate than predictions from other
      available methods, which ignore the effect of selection on deltaF. Predictions
      were accurate for schemes with up to 20 sires. Predicted deltaF was somewhat too
      low for schemes with more than 20 sires, which was due to the use of simple
      linear models to predict genetic contributions. The present method provides a
      computationally feasible (i.e., deterministic) tool to consider both the rate of
      inbreeding and the rate of genetic gain when optimizing livestock improvement
      schemes.

PMID- 11325189
TI  - A comprehensive search for quantitative trait loci affecting growth and carcass
      composition of cattle segregating alternative forms of the myostatin gene.
AB  - The objective of this study was to identify quantitative trait loci for
      economically important traits in two families segregating an inactive copy of the
      myostatin gene. Two half-sib families were developed from a Belgian Blue x MARC
      III (n = 246) and a Piedmontese x Angus (n = 209) sire. Traits analyzed were
      birth, weaning, and yearling weight (kg); preweaning average daily gain (kg/d);
      postweaning average daily gain (kg/d); hot carcass weight (kg); fat depth (cm);
      marbling score; longissimus muscle area (cm2); estimated kidney, pelvic, and
      heart fat (%); USDA yield grade; retail product yield (%); fat yield (%); and
      wholesale rib-fat yield (%). Meat tenderness was measured as Warner-Bratzler
      shear force at 3 and 14 d postmortem. The effect of the myostatin gene was
      removed using phase information from six microsatellite markers flanking the
      locus. Interactions of the myostatin gene with other loci throughout the genome
      were also evaluated: The objective was to use markers in each family, scanning
      the genome approximately every 25 to 30 centimorgans (cM) on 18 autosomal
      chromosomes, excluding 11 autosomal chromosomes previously analyzed. A total of
      89 markers, informative in both families, were used to identify genomic regions
      potentially associated with each trait. In the family of Belgian Blue
      inheritance, a significant QTL (expected number of false-positives = 0.025) was
      identified for marbling score on chromosome 3. Suggestive QTL for the same family
      (expected number of false-positives = 0.5) were identified for retail product
      yield on chromosome 3, for hot carcass weight and postweaning average daily gain
      on chromosome 4, for fat depth and marbling score on chromosome 8, for 14-d
      Warner-Bratzler shear force on chromosome 9, and for marbling score on chromosome
      10. Evidence suggesting the presence of an interaction for 3-d Warner-Bratzler
      shear force between the myostatin gene and a QTL on chromosome 4 was detected. In
      the family of Piedmontese and Angus inheritance, evidence indicates the presence
      of an interaction for fat depth between the myostatin gene and chromosome 8, in a
      similar position where the evidence suggests the presence of a QTL for fat depth
      in the family with Belgian Blue inheritance. Regions identified underlying QTL
      need to be assessed in other populations. Although the myostatin gene has a
      considerable effect, other loci with more subtle effects are involved in the
      expression of the phenotype.

PMID- 11325190
TI  - Locomotor activity, core body temperature, and circadian rhythms in mice selected
      for high or low heat loss.
AB  - Daily locomotor activity, core body temperature, and their circadian rhythms were
      measured in lines of mice selected for high (MH) or low (ML) heat loss and
      unselected controls (MC). Lines were created by selecting for 16 generations in
      each of three replicates. Collection of locomotor activity and core temperature
      data spanned Generations 20 and 21 for a total of 352 mice. Physical activity and
      core body temperature data were accumulated using implanted transmitters and
      continuous automated collection. Measurement for each animal was for 3 d.
      Activity was recorded for each half hour and then averaged for the day;
      temperature was averaged daily; circadian rhythm was expressed in 12-h (light vs
      dark) or 6-h periods as well as by fitting cyclic models. Activity means were
      transformed to log base 2 to lessen heterogeneity of variance within lines. Heat
      loss for a 15-h period beginning at 1630 and feed intake for 7 d were measured on
      74 additional mice in order to estimate the relationship between locomotor
      activity and heat loss or feed intake. Selection lines were different (P < 0.01)
      for both locomotor activity and core body temperature. Differences were due to
      selection (MH-ML, P < 0.01), and there was no evidence of asymmetry of response
      (P > 0.38). Retransformed from log base 2 to the scale of measurement, mean
      activity counts were 308, 210, and 150 for MH, MC, and ML, respectively. Mean
      core temperatures were 37.2, 36.9, and 36.7 degrees C for MH, MC, and ML (P <
      0.01), respectively. Females had greater physical activity (P < 0.01) and body
      temperature (P < 0.01) than males. There was no evidence of a sex x selection
      criterion interaction for either activity or temperature (P > 0.20). Overall
      phenotypic correlation between body temperature and log base 2 activity was 0.43
      (P < 0.01). Periods during the day were different for both 12- and 6-h analyses
      (P < 0.01), but there were no period x selection criterion interactions (P > 0.1)
      for physical activity or body temperature. More sensitive cyclic models revealed
      significant (P < 0.01) 24-, 12-, 8-, and 6-h cycles that differed (P < 0.01)
      among lines. Estimated differences between MH and ML mice in feed intake and heat
      loss due to locomotor activity were 36 and 11.5%, respectively. Variation in
      activity thus contributed to variation in feed intake.

PMID- 11325191
TI  - Usefulness of subjective ovine milk scores: II. Genetic parameter estimates.
AB  - Genetic parameters for a subjective milk score given to ewes within 24 h of
      parturition were estimated to determine the usefulness of milk score as a
      selection trait to improve milk production, which influences total litter weight
      weaned. Heritability of milk score and the genetic correlation of milk score with
      litter weight weaned were estimated by REML separately for four sheep breeds,
      Rambouillet (n = 1,731), Targhee (n = 1,638), Columbia (n = 1,731), and Polypay
      (n = 1,129). Litter weight weaned was the total weight of lambs weaned at
      approximately 120 d of age under a western range production system. Observed
      heritability estimates for milk score at first parity were moderate and similar
      among breeds, ranging from 0.18 to 0.32. Heritability estimates adjusted for a
      binomial distribution of milk scores at first parity were high (Columbia, 0.43;
      Polypay, 0.35; Rambouillet, 0.50; Targhee, 0.84). Estimates of observed
      heritability for second-parity milk score were moderate to high, ranging from
      0.23 to 0.46. Milk score at first or second parity was genetically correlated
      with milk score records at maturity (third parity and greater), with estimates
      ranging from 0.69 to 1.00. Milk score and litter weight weaned were genetically
      correlated at first or second parity in Rambouillet (r(g) = 1.00) and Targhee
      breeds (r(g) = 1.00 and 0.61, respectively), but not in the Columbia and Polypay
      breeds. Estimates of heritability for lifetime records for milk score ranged from
      0.16 to 0.26 across breeds. Estimates of genetic correlations of annual lifetime
      milk score records with litter weight weaned were high (Columbia, 1.00; Polypay,
      0.81; Rambouillet, 1.00; and Targhee, 0.77). Repeatability estimates for milk
      score were similar across breeds, 0.23 for Columbia, Rambouillet, and Targhee
      ewes and 0.28 for Polypay ewes. Milk score measured at first or second parity may
      be a good predictor of future potential milking ability. Further, milk score can
      be used as a selection trait to improve maternal ability for increasing litter
      weight weaned. The need for increasing ewe milking performance and lamb growth
      rate at first parity in commercial range sheep production systems may be
      addressed by selection for milk score at first parity.

PMID- 11325192
TI  - Profile of ligand binding to the porcine beta2-adrenergic receptor.
AB  - Chinese hamster ovary cells expressing the porcine beta2-adrenergic receptor
      (betaAR) were used to determine the binding kinetics of agonists and antagonists
      by competitive displacement of the radioligand [125I]iodocyanopindolol. Several
      purported agonists, including isoproterenol, epinephrine, norepinephine,
      dobutamine, salbutamol, and terbutaline, exhibited dual-affinity displacement
      curves, which is characteristic of agonist binding to betaAR. In each case, the
      addition of guanosine triphosphate (GTP) eliminated the high-affinity state and
      resulted in a one-site displacement curve. All of the antagonists modeled to only
      one site in the presence or absence of GTP. Several ligands, including ones used
      to promote animal growth (clenbuterol, L-644,969, and ractopamine) and the
      beta3AR-selective agonist BRL 37344 modeled to only one site, suggesting that
      these ligands would not be full agonists at the porcine beta2AR (pbeta2AR). Most
      of the tested ligands exhibited binding affinities that were similar to published
      values for the beta2AR from other species. However, several exceptions were
      observed. The BRL 37344 ligand bound the pbeta2AR with a 10-fold higher affinity
      than the human beta2AR, and the Kd of this was similar to Kd values reported for
      the human and rat beta3AR. The Kd of the pbeta2AR for ICI 118,551 was 50-fold
      higher than that for the beta2AR from rats and humans. For both BRL 37344 and ICI
      118,551 the subtype-selective character of these ligands was different in the pig
      compared with the human and rat. These data demonstrate the value of using
      species-specific betaAR for selection of agonists and antagonists. Further, these
      data support the growing evidence that few ligands are full agonists for pbetaAR
      and that binding data may be useful for identifying ligands with full agonist
      potential.

PMID- 11325193
TI  - Tasco-Forage: IV. Influence of a seaweed extract applied to tall fescue pastures
      on sensory characteristics, shelf-life, and vitamin E status in feedlot-finished
      steers.
AB  - Tasco-Forage is an Ascophyllum nodosum seaweed-based product that has increased
      antioxidant activity in both plants and animals. Endophyte (Neotyphodium
      coenophialum ([Morgan-Jones and Gams] Glenn, Bacon, and Hanlin)-infected and
      uninfected tall fescue (Festuca arundinacea Schreb.) pastures in Virginia and
      Mississippi during 1997 were treated or not with 3.4 kg Tasco/ha in April and
      July. There were two replications of each treatment at each location. Forty-eight
      steers (6/replication) grazed pastures at each location (n = 96) from April to
      October prior to transportation to Texas Tech, Lubbock, for finishing during a
      160-d period in the feedlot. Blood (antemortem) and liver (postmortem) samples
      were collected. After slaughter and chilling, the left strip loins (IMPS #180)
      were collected from three randomly selected steers from within each pasture
      replication (n = 48). Strip loins were vacuum-packaged and stored at 2 degrees C.
      At postmortem d 7, 14, 21, and 28, strip loins were removed from packaging and
      fabricated into 2.54-cm steaks. Following each fabrication day postmortem, the
      strip loins were repackaged and stored at 2 degrees C until the following
      postmortem time. After the prescribed fabrication, steaks were overwrapped with
      polyvinyl chloride film, subjected to simulated retail display at 2 degrees C for
      up to 3 d, and subjective and objective color were evaluated daily by a trained
      panel. Steaks from Mississippi steers that had grazed Tasco-treated fescue
      retained higher (P < 0.05) CIE a* color scores throughout retail display. Steaks
      were more uniform and had less discoloration and less browning (P < 0.05) if they
      were from steers that had grazed Tasco-treated fescue, and the effect was
      greatest for steers from Mississippi (location x Tasco interaction; P < 0.05).
      The endophyte in tall fescue may decrease uniformity and increase lean
      discoloration and two-toning of beef steaks when removed from vacuum packaging on
      or beyond d 21 postmortem (endophyte x Tasco x postmortem day interaction: P <
      0.05). Vitamin E in liver was increased (P < 0.06) and serum vitamin E was
      decreased (P < 0.09) in steers that had grazed the treated pastures. These
      experiments indicated that Tasco applied to tall fescue during the grazing season
      can improve color stability and extend beef shelf-life, particularly in cattle
      grazing infected tall fescue. The mode of action of Tasco is not clear, but
      antioxidants and specific vitamins may be involved.

PMID- 11325194
TI  - Effect of dietary modification of muscle long-chain n-3 fatty acid on plasma
      insulin and lipid metabolites, carcass traits, and fat deposition in lambs.
AB  - In a previous study we showed that feeding fish meal significantly increased
      muscle long chain n-3 fatty acids (FA) and hot carcass weight. In this study we
      compared the effect of fish meal and fish oil on increasing muscle long-chain FA.
      We also investigated whether the increase in carcass weight was due to the effect
      of dietary enrichment of muscle long-chain n-3 FA on muscle membrane
      phospholipids and(or) to rumen by-pass protein provided by fish meal. Forty
      crossbred ([Merino x Border Leicester] x Poll Dorset) wether lambs between 26 and
      33 kg BW were randomly assigned to one of five treatments: 1) basal diet of
      oaten:lucerne chaff (Basal); 2) Basal + fish meal (9% DM) = FM; 3) Basal + fish
      oil (1.5% DM) with protected sunflower meal (9% DM ) = FOSMP; 4) Basal + fish oil
      (1.5% DM) = FO; or 5) Basal + protected sunflower meal (10.5% DM) = SMP. Daily
      intake of ME (9.60 - 10.5 MJ ME/d) and CP (150 to 168 g/d) in all treatments was
      kept similar by varying the ratio of oaten:lucerne chaff and by feeding the
      animals at 90% ad libitum intake. Blood samples were collected at the start of
      the experiment and on the day (d 42) prior to slaughter. Lambs were then
      slaughtered at a commercial abattoir. At 24 h postmortem carcass traits were
      measured and longissimus thoracis muscle taken for analysis of FA of phospholipid
      and triglyceride fractions. Lambs fed FO and FOSMP showed a marked increase in
      muscle longchain n-3 FA (P < 0.001) and a reduction in magnitude of the rise in
      insulin concentration (P < 0.001) after feeding compared with lambs fed Basal and
      SMP diets. Lambs in FM had a moderate increase (P < 0.001) in muscle long-chain n
      3 FA content. Compared with Basal diet, both plasma total cholesterol (P < 0.02)
      and high-density lipoprotein cholesterol (P < 0.001) levels were greater in SMP
      and less in FO and FOSMP treatments. The i.m. fat content was reduced (P < 0.05)
      in FM and FO treatments, but carcass weight was increased only with fish meal (P
      < 0.03). Adding SMP to FO produced muscle with an intermediate level of i.m. fat,
      whereas muscle long-chain n-3 FA, i.m. fat, and insulin concentration were
      unchanged with SMP treatment. These results indicate that an increase in carcass
      weight in FM may be due to the supply of ruminally undegraded protein. They also
      suggest that fish oil along with fish meal can increase long-chain n-3 FA content
      in phospholipid of muscle membrane. This may be associated with reduced i.m. fat
      content and altered insulin action and lipoprotein metabolism.

PMID- 11325195
TI  - Technical note: comparison of myofibril fragmentation index from fresh and frozen
      pork and lamb longissimus.
AB  - The myofibril fragmentation index (MFI) is strongly associated with indices of
      meat tenderness, such as Warner-Bratzler shear force and sensory tenderness. The
      MFI is normally determined on fresh muscle. It is not known whether this index
      can be determined on frozen muscle. The objective of this experiment was,
      therefore, to determine whether there is a difference between MFI values of fresh
      and frozen lamb and pork longissimus. To compare the effect of freezing on MFI,
      longissimus samples were obtained from eight lamb carcasses at 1, 3, and 15 d
      postmortem and longissimus samples were obtained from 12 pork carcasses at 3 d
      postmortem. For each sample, MFI was conducted on both fresh muscle and snap
      frozen muscle (frozen in liquid nitrogen and stored 23 to 26 d at -70 degrees C).
      The R2 between MFI of fresh and frozen muscle was 0.94 and 0.92 for lamb and pork
      longissimus, respectively. The differences between fresh and frozen MFI were not
      significant for either species (P > 0.05). These results indicate that it is not
      necessary to determine MFI on fresh muscle.

PMID- 11325196
TI  - Factors influencing consumer demand for U.S. pork exported to the Republic of
      Korea (South Korea).
AB  - The potential market for single-ribbed bellies and Boston butts in South Korea
      was characterized and quantitative selection criteria were identified for use by
      U.S. packers when selecting pork for export. South Korean retail meat market
      managers and traders/wholesalers in Seoul and Pusan were interviewed and asked to
      identify the quality attributes that are considered when making pork-purchasing
      decisions. In addition, pork labeling characteristics and meat display case
      measurements and space allocations were recorded in each retail store. Data from
      box labels were recorded in retail storage coolers to characterize pork products
      currently being merchandized in South Korea. Sample retail packages of belly and
      butt slices were collected and sent to a commercial laboratory for analysis of
      iodine values, ether-extractable fat content, total aerobic plate count (APC),
      total coliform count (TCC), and generic Escherichia coli count (ECC). No quality
      attributes of U.S. products exceeded the expectations of retailers. Quality
      attributes of U.S. pork products that exceeded the expectations of traders
      included presence of foreign material, marbling, tenderness, juiciness, flavor,
      and overall eating satisfaction. Traders/wholesalers assigned negative ratings
      for overall workmanship and adherence to purchase criteria for U.S. pork
      products. Retail APC for South Korean belly samples were higher (P < 0.05) than
      APC for U.S. belly samples. Retail TCC and ECC for butts and belly samples and
      APC for butt samples did not differ by country of origin. Retail prices for South
      Korean bellies were higher (P < 0.05) than prices for retail U.S. and Danish
      bellies. Pork butt prices did not differ (P > 0.05) by country of origin. Beef,
      pork, and poultry products comprised 66.8, 27.8, and 5.4%, respectively, of the
      total meat display case frontage. U.S. beef products occupied, on average, 18% of
      the total beef display area, whereas U.S. pork products comprised 2.6% of the
      total pork display case area.

PMID- 11325197
TI  - Supranutritional oral supplementation with vitamin D3 and calcium and the effects
      on beef tenderness.
AB  - Ultimate meat tenderness can be influenced by numerous preslaughter and
      postmortem management techniques. Increased levels of intracellular Ca2+, through
      postmortem injection, infusion, or marination, have been shown to improve the
      tenderness of cooked meat products. Oral supplementation with vitamin D3
      effectively increases serum Ca2+ and has been hypothesized to increase muscle
      Ca2+ content, the activity of muscle proteases, and thus the tenderness of cooked
      beef. Individual Charolais x Hereford heifers (n = 191) were assigned to an
      unsupplemented control group or groups that were supplemented via oral bolus (for
      dose regulation purposes) with one of seven levels of vitamin D3 (1, 2, 3, 4, or
      5 x 10(6) IU D3/d, 2 x 10(6) IU DS/d plus 75 g CaCO3 or 4 x 106 IU D3/d plus 75 g
      CaCO3) for 2, 4, 6, or 8 d antemortem. Individual feedlot performance, serum Ca2+
      levels, and carcass data were collected, and eight longissimus steaks/carcass
      were used to obtain Warner-Bratzler shear force values measured at 2, 7, 14, and
      21 d postmortem for longissimus steaks cooked to 70 degrees or 85 degrees C.
      Cattle supplemented with 4 x 10(6) IU D3/d plus 75 g of CaCO3 had lower daily
      feed intake (as-fed) and reduced (P < 0.05) average daily gains compared with
      controls during the 8-d supplementation period. Additionally, supplemented cattle
      had numerically higher dressing percentages, possibly due to less fill at the
      time of slaughter, because carcass weights and USDA yield grades did not differ
      (P > 0.05) across treatment groups. Supplementation with 1, 2, 3, 4, or 5 x 10(6)
      IU D3/d, for 2 or more days, increased (P < 0.05) serum Ca2+ concentrations
      compared with controls. Whereas cattle that received additional dietary Ca2+ in
      the form of CaCO3 had the lowest blood serum Ca2+ concentration. Although blood
      serum Ca2+ was increased, supplementation with any level of vitamin D3 for any
      length of time up to 8 d did not improve (P > 0.05) Warner-Bratzler shear force
      at 2, 7, 14, or 21 d of postmortem aging compared with controls when steaks were
      cooked to final internal temperatures of either 70 (control means 6.27, 4.91,
      4.64, and 3.80 kg, respectively) or 85 degrees C (control means 7.31, 5.32, 4.69,
      and 4.46 kg, respectively). Results indicated that oral supplementation with
      vitamin D3 (at high or low doses) for 2 to 8 d before slaughter increased serum
      Ca2+ concentration but does not improve cooked longissimus tenderness.

PMID- 11325198
TI  - Fruit and vegetable fiber fermentation by gut microflora from canines.
AB  - The objective of this study was to assess fermentability by canine gut microflora
      to include shortchain fatty acid (SCFA) production, organic matter (OM)
      disappearance, and gas production of vegetable and fruit fiber sources compared
      to fiber standards (psyllium, citrus pectin, and Solka Floc). Fiber sources
      included apple pomace, carrot pomace, flaxseed, fruit blend (mixture of peach,
      almond, nectarine, and plum), grape pomace, pea hulls, pistachio, and tomato
      pomace. Substrates were fermented in vitro for 4, 12, and 24 h with fecal flora
      obtained from three healthy dogs. Citrus pectin had the highest OM disappearance,
      SCFA production, and gas production at all times of fermentation; psyllium was
      intermediate and Solka Floc was lowest. A wide variation in fermentability was
      noted among the vegetable and fruit fiber sources. Apple pomace, carrot pomace,
      and flaxseed had the greatest fermentability as assessed by OM disappearance. Pea
      hulls and tomato pomace had intermediate OM disappearances, and fruit blend,
      grape pomace, and pistachio were poorly fermented. Carrot pomace produced the
      largest amounts of gas and SCFA. Apple pomace produced high concentrations of gas
      but intermediate concentrations of SCFA. Pea hulls and tomato pomace produced
      intermediate concentrations of gas and SCFA, whereas flaxseed, fruit blend, grape
      pomace, and pistachio produced low amounts of these fermentation products. For
      all substrates collectively, OM disappearance was highly correlated with both gas
      production (r2 = 0.782 and 0.723 for 12- and 24-h values, respectively) and SCFA
      production (r2 = 0.737 and 0.738 for 12- and 24-h values, respectively). In
      general, OM disappearance, gas production, and SCFA production were related to
      the insoluble:soluble fiber ratio in the samples; as the insoluble:soluble ratio
      decreased (increased soluble fiber), the OM disappearance, gas production, and
      SCFA production increased.

PMID- 11325199
TI  - Increased responsiveness to dietary lysine deficiency of pectoralis major muscle
      protein turnover in broilers selected on breast development.
AB  - It has been previously established that growth and carcass qualities of chicks
      are modified by genotype and dietary amino acid supply. In this study, we
      evaluated the effects of lysine deficiency and genetic selection on muscle
      protein metabolism. Chicks originating from an experimental line selected for
      breast development (QL) and its control line (CL) were provided ad libitum access
      to isoenergetic diets containing 20% crude protein but differing in their lysine
      content (0.75 or 1.01%). Protein fractional synthesis rates (FSR) were measured
      in vivo in the pectoralis major and sartorius muscles of 3-wk-old chickens
      (flooding dose of [3H]phenylalanine). Fractional breakdown rates (FBR) were
      estimated as the difference between synthesis and deposition. Lysine deficiency
      reduced (P < 0.001) growth performance and muscle weights and increased (P <
      0.05) muscle FSR, capacity for protein synthesis (muscle RNA:Protein, Cs) and
      FBR. Although QL birds grew faster and had heavier pectoralis major muscles than
      CL birds (P < 0.05), there was no line difference in sartorius weight (P = 0.15).
      No difference between the lines was observed in sartorius protein metabolism (P >
      0.14). In the pectoralis major muscle, chicks of both lines receiving an adequate
      lysine intake also exhibited similar protein turnover rates. However, in chicks
      fed the lysine-deficient (0.75% lysine) diet, FSR and Cs were higher in QL than
      in CL chicks (P < 0.05), and FBR tended (P = 0.07) to be higher in QL chicks.
      This increased protein turnover in the QL birds on the lysine-deficient diet
      suggests that the responsiveness of muscle protein metabolism to amino acid
      supply is modified by genetic selection for breast development.

PMID- 11325200
TI  - Effect of pharmacological concentrations of zinc oxide with or without the
      inclusion of an antibacterial agent on nursery pig performance.
AB  - A study involving nine research stations from the NCR-42 Swine Nutrition
      Committee used a total of 1,978 crossbred pigs to evaluate the effects of dietary
      ZnO concentrations with or without an antibacterial agent on postweaning pig
      performance. In Exp. 1, seven stations (IA, MI, MN, MO, NE, ND, and OH) evaluated
      the efficacy of ZnO when fed to nursery pigs at 0, 500, 1,000, 2,000, or 3,000 mg
      Zn/kg for a 28-d postweaning period. A randomized complete block experiment was
      conducted in 24 replicates using a total of 1,060 pigs. Pigs were bled at the 28
      d period and plasma was analyzed for Zn and Cu. Because two stations weaned pigs
      at < 15 d (six replicates) and five stations at > 20 d (18 replicates) of age,
      the two sets of data were analyzed separately. The early-weaned pig group had
      greater (P < 0.05) gains, feed intakes, and gain:feed ratios for the 28-d
      postweaning period as dietary ZnO concentration increased. Later-weaned pigs also
      had increased (P < 0.01) gains and feed intakes as the dietary ZnO concentration
      increased. Responses for both weanling pig groups seemed to reach a plateau at
      2,000 mg Zn/kg. Plasma Zn concentrations quadratically increased (P < 0.01) and
      plasma Cu concentrations quadratically decreased (P < 0.01) when ZnO
      concentrations were > 1,000 mg Zn/kg. Experiment 2 was conducted at seven
      stations (KY, MI, MO, NE, ND, OH, and OK) and evaluated the efficacy of an
      antibacterial agent (carbadox) in combination with added ZnO. The experiment was
      a 2 x 3 factorial arrangement in a randomized complete block design conducted in
      a total of 20 replicates. Carbadox was added at 0 or 55 mg/kg diet, and ZnO was
      added at 0, 1,500, or 3,000 mg Zn/ kg. A total of 918 pigs were weaned at an
      average 19.7 d of age. For the 28-d postweaning period, gains (P < 0.01), feed
      intakes (P < 0.05), and gain:feed ratios (P < 0.05) increased when dietary ZnO
      concentrations increased and when carbadox was added. These responses occurred in
      an additive manner. The results of these studies suggest that supplemental ZnO at
      1,500 to 2,000 mg Zn/kg Zn improved postweaning pig performance, and its
      combination with an antibacterial agent resulted in additional performance
      improvements.

PMID- 11325201
TI  - Comparative effects of high dietary levels of organic and inorganic selenium on
      selenium toxicity of growing-finishing pigs.
AB  - This experiment evaluated the effect of high dietary Se levels using organic or
      inorganic Se on the selenosis responses in growing-finishing swine. A 2 x 4
      factorial arrangement of treatments in a randomized complete block design was
      conducted in two replicates. Sodium selenite or Se-enriched yeast was added at 5,
      10, 15, or 20 ppm Se to corn-soybean meal diets. A basal diet without added Se
      was a ninth treatment group. Ninety crossbred barrows initially averaging 24.7 kg
      BW were allotted at five pigs per pen. Pigs were bled at 3-wk intervals and
      plasma Se, glutathione peroxidase (GSH-Px) activity, glutamic oxalacetic
      transaminase (PGOT), hemoglobin, packed cell volume, and blood cell Se
      concentration were measured. After 12 wk, pigs were killed and various tissues
      and bile were collected for Se analyses. Pig body weights, daily gains, and feed
      intakes were similar for both Se sources when provided at < or = 5 ppm Se, but
      each measurement declined in a different manner for each Se source as the dietary
      Se level increased. The decline was more rapid when the inorganic rather than
      organic Se source was fed, resulting in interaction responses (P < 0.01). Hair
      loss (alopecia) and separation of the hoof at the coronary band site occurred at
      > or = 10 ppm inorganic Se but at > or = 15 ppm organic Se level. Plasma GSH-Px
      activity increased (P < 0.01) when high dietary Se levels of either Se source was
      fed. Plasma and blood cell Se increased at each period as dietary Se level
      increased (P < 0.01) and was greater when organic Se was provided (P < 0.05).
      Blood cell Se concentration reached a plateau when inorganic Se, but not when
      organic Se, was fed and increased as the experiment progressed. This resulted in
      a three-way interaction (P < 0.01). Plasma GOT activity at the 12-wk period was
      elevated when inorganic Se was provided at > or = 15 ppm Se but not when organic
      Se was fed, resulting in an interaction (P < 0.05). Tissue Se concentrations
      increased as dietary Se level increased and when organic Se was provided,
      resulting in interaction responses (P < 0.05). Bile was a yellow color when the
      basal diet was fed but was dark brown at > 10 ppm inorganic Se and at 20 ppm when
      organic Se was provided. Bile Se increased as dietary Se level increased (P <
      0.01). These results suggest that dietary Se from inorganic or organic sources
      was toxic at > or = 5 ppm Se, but subsequent selenosis effects were more severe
      and occurred sooner when sodium selenite was the Se source.

PMID- 11325202
TI  - Effect of dietary selenium source, level, and pig hair color on various selenium
      indices.
AB  - The first experiment evaluated the effects of feeding various levels of Se, two
      Se sources, and hair color on selenosis responses in growing-finishing pigs. The
      study conducted in two replicates was a 2 x 6 x 2 factorial arrangement in a
      split-plot design. Sodium selenite and Se-enriched yeast added at 0.3, 1, 3, 5,
      7, and 10 ppm Se served as the main plot and pig hair color as the subplot. A
      total of 96 crossbred pigs were allotted and fed their treatment diets for a 12
      wk period. White and dark (red or black) hair samples were collected from the
      dorsal-midline at the 4-, 8-, and 12-wk periods from one pig of each hair color
      from each treatment pen. Lower pig weights (P < 0.10) and daily gains (P < 0.05)
      occurred as dietary Se level increased when pigs were fed either Se source.
      Selenosis responses were somewhat more severe, when the inorganic Se source was
      fed. Alopecia and hoof separation were encountered after the 8-wk period when
      pigs were fed inorganic rather than organic Se. Plasma Se increased as dietary
      level increased (P < 0.01), when organic Se was provided (P < 0.01), and was
      higher (P < 0.05) when pigs were white-haired. A time x hair color x dietary Se
      level interaction (P < 0.05) occurred, in which hair Se concentration was higher
      in dark- than in white-colored pigs and increased as dietary Se level increased
      as the experiment progressed. The correlation coefficient between dietary Se
      level and hair Se concentration averaged 0.90 (P < 0.01). Cysteine was the amino
      acid in the highest concentration in hair, but this and other amino acids were
      not affected by Se level, Se source, or hair color. A second experiment was a 3 x
      6 factorial arrangement in a split-plot design with three 9-mo-old gilts from
      each of the Yorkshire, Duroc, and Hampshire breeds to determine whether hair Se
      concentration differed by body location and breed. Hair samples were collected
      from the shoulder, back, rump, front-leg, belly, and hind-leg areas. Hair Se
      concentration was higher in red- and white-haired pigs and lower in black-haired
      gilts (P < 0.01). Higher hair Se concentrations (P < 0.05) occurred from the
      lower than from the upper body areas. Our results suggest that selenosis occurs
      at dietary levels > 5 ppm and that white-haired pigs exhibit alopecia sooner than
      dark-haired pigs. No difference in hair Se concentration occurred when diets were
      < 1 ppm Se, but as dietary Se level increased dark-haired pigs retained more Se
      in their hair than white-haired pigs.

PMID- 11325203
TI  - Prolonged feeding of high dietary levels of organic and inorganic selenium to
      gilts from 25 kg body weight through one parity.
AB  - An experiment evaluated the selenosis effects from feeding high dietary Se levels
      of organic or inorganic Se sources to growing gilts with the dietary treatments
      continued through a reproductive cycle. A total of 88 gilts were allotted at 25
      kg BW to two replicates in a 2 x 4 factorial arrangement in a randomized complete
      block design. Inorganic Se (sodium selenite) or organic (Se-enriched yeast) Se
      were added to diets at 0.3, 3, 7, or 10 ppm Se. At 105 kg BW, four gilts per
      treatment were killed and livers collected for Se analysis. At 8 mo of age, three
      gilts from each treatment group were bred and fed their treatment diet, with
      subsequent reproductive performance and selenosis effects evaluated. Serum
      collected at various intervals in gilts, sows, and progeny measured glutathione
      peroxidase activity and Se concentrations. Sow colostrum and milk was analyzed
      for their Se concentrations. Three pigs per treatment were killed before
      colostrum consumption and at weaning (14 d) and tissue collected for Se analysis.
      Gilt gains (P < 0.01) and feed intakes (P < 0.05) declined during the grower
      period as dietary Se level increased for both Se sources. Serum and liver Se
      concentrations increased as dietary Se level increased and was higher when
      organic Se was fed (P < 0.01). Sows fed dietary Se levels at > 7 ppm had lower
      gestation weights (P < 0.05) and lower lactation feed intakes (P < 0.05). As Se
      level increased, sows fed organic Se had a lower number of live pigs born (P <
      0.05) and weaned fewer pigs (P < 0.05) with lower litter gains (P < 0.05) than
      did sows fed inorganic Se. Colostrum and milk Se concentrations increased as
      dietary Se levels increased particularly when organic Se was fed (P < 0.01).
      Neonatal and weanling pig tissue Se and serum Se concentrations increased as
      dietary Se level increased and when organic Se was fed, resulting in interaction
      responses (P < 0.01). Pigs nursing sows fed > 7 ppm inorganic Se had hoof
      separation and alopecia, with the severity being greater when sows were fed the
      inorganic Se source. These results suggest that both the organic and inorganic Se
      sources were toxic when fed at 7 to 10 ppm for a prolonged period, but organic Se
      seemed to express the selenotic effects more on reproductive performance, whereas
      inorganic Se was more detrimental during lactation.

PMID- 11325204
TI  - Effects of betaine, pen space, and slaughter handling method on growth
      performance, carcass traits, and pork quality of finishing barrows.
AB  - An experiment was conducted to determine the effects of betaine, pen space, and
      preslaughter handling method on growth, carcass traits, and pork quality of
      finishing barrows. For the growth trial, a 2 x 2 factorial arrangement of
      treatments was used: betaine (0 or 0.250%) and(or) pen space (m2/pig; adequate,
      0.035 BW0.67 kg, or inadequate, 0.025 BW0.67 kg). Each treatment was replicated
      five times with four barrows per replicate. At trial termination, two barrows
      from each pen were selected to receive either minimal or normal preslaughter
      handling. Reducing pen space decreased (P < 0.05) overall ADG and gain:feed and
      tended (P = 0.12) to decrease overall ADFI. Betaine had no affect (P > 0.10) on
      overall ADG, ADFI, or gain:feed. Pigs fed betaine had decreased (P < 0.10)
      carcass length. Other carcass and ham measurements were not affected (P > 0.10)
      by betaine. Pigs with inadequate pen space had increased (P < 0.10) ultimate pH,
      subjective color, cooking loss (fresh and frozen chop), and shear force but
      decreased rectal temperature, loin muscle CIE L*, biceps femoris CIE b*, and drip
      loss. Pigs subjected to minimal preslaughter handling had decreased (P < 0.10)
      rectal temperature, plasma cortisol, loin muscle CIE b*, and fresh chop total
      loss (drip + cooking loss). Pigs fed betaine had increased (P < 0.01) initial pH
      and decreased (P < 0.10) drip loss (fresh chop). Cooking loss and total loss
      (frozen chop) were decreased in pigs fed betaine with adequate pen space but
      increased in pigs fed betaine with inadequate pen space (betaine x pen space, P <
      0.01). Pigs fed betaine may have improved pork quality.

PMID- 11325205
TI  - Effect of whole-body vibration in the vertical axis on cortisol and
      adrenocorticotropic hormone levels in piglets.
AB  - Vibration, being a consequence of motion during transport, may impair the welfare
      of pigs. Therefore, the primary objectives of this study were 1) to evaluate
      during transport simulation the use of ACTH and cortisol plasma levels, which are
      part of a basic adaptation mechanism of pigs and 2) to define comfort conditions
      for pigs related to the frequency and acceleration of vibration. Pigs with a body
      weight between 20 and 25 kg were vibrated in the vertical direction for 2 h at 2,
      4, 8, and 18 Hz, in combination with root mean square acceleration magnitudes of
      1 or 3 m/s2. Blood was sampled at regular intervals before, during, and after
      vibration as the pig's behaviors were recorded. Data on ACTH, cortisol, and
      behavior could be collected from 104 vibrated pigs and 21 controls. In addition,
      eight animals (3 controls, 5 vibrated) were treated with 0.1 mg of
      dexamethasone/kg BW, eight animals (3 controls, 8 vibrated) with 0.1 mg
      naloxone/kg BW, and six (2 controls, 4 vibrated) with a physiological salt
      solution. Blood samples were taken and products were administrated via an
      intravenous catheter. The pigs spent less time lying during both hours of
      vibration treatment than during control conditions. Compared with 2 and 4 Hz,
      time spent lying was 10 times shorter at 8 Hz and 18 times shorter at 18 Hz. At
      1030, ACTH levels were significantly higher than basal levels in animals vibrated
      at 2 (P < 0.0001), 4 (P < 0.002), and 18 Hz (P < 0.0006). After 1 h, levels
      returned to basal values. Cortisol levels increased very rapidly after the
      beginning of vibration (P < 0.0001) and remained higher until 1 h after cessation
      of vibration (P < 0.003). An inferrence of the lines of equal responses for ACTH
      and cortisol indicated that, in the beginning of vibration exposure, pigs were
      extremely susceptible to vibrations at lower frequencies (2 and 4 Hz), whereas at
      the end of vibration exposure the responses were higher at 18 Hz. The application
      of dexamethasone and naloxone underpinned the emotional component of the response
      strategy of pigs to vibration. Hence, vibration during transport should be
      minimized in order to enhance the adaptive capacities of pigs.

PMID- 11325206
TI  - Efficacy of an intravaginal progesterone insert and an injection of PGF2alpha for
      synchronizing estrus and shortening the interval to pregnancy in postpartum beef
      cows, peripubertal beef heifers, and dairy heifers.
AB  - The objective was to test the efficacy of an intravaginal progesterone insert and
      injection of PGF2alpha for synchronizing estrus and shortening the interval to
      pregnancy in cattle. Cattle were assigned to one of three treatments before a 31
      d breeding period that employed artificial insemination. Control cattle were not
      treated, and treated cattle were administered PGF2alpha or an intravaginal
      progesterone-releasing insert (CIDR) for 7 d and treated with PGF2alpha on d 6.
      The treatments were applied in one of three experiments that involved postpartum
      beef cows (Exp. 1; n = 851; 56+/-0.6 d postpartum), beef heifers (Exp. 2; n =
      724; 442.5+/-2.8 d of age), and dairy heifers (Exp. 3; n = 260; 443.2+/-4.5 d of
      age). Luteal activity before treatment was determined for individual cattle based
      on blood progesterone concentrations. In Exp. 1, there was a greater incidence of
      estrus during the first 3 d of the breeding period in CIDR+PGF2alpha-treated cows
      compared with PGF2alpha-treated or control cows (15, 33, and 59% for control,
      PGF2alpha, and CIDR+PGF2alpha, respectively; P < 0.001). The improved estrous
      response led to an increase in pregnancy rate during the 3-d period (7, 22, and
      36% for control, PGF2alpha, and CIDR+PGF2alpha, respectively; P < 0.001) and
      tended to improve pregnancy rate for the 31-d breeding period for cows treated
      with CIDR+PGF2alpha, (50, 55, and 58% for control, PGF2alpha, and CIDR+PGF2alpha,
      respectively, P = 0.10). Improvements in rates of estrus and pregnancy after
      CIDR+PGF2alpha, were also observed in beef heifers. Presence of luteal activity
      before the treatment period affected synchronization and pregnancy rates because
      anestrous cows (Exp. 1) or prepubertal heifers (Exp. 2) had lesser
      synchronization rates and pregnancy rates during the first 3 d of the breeding
      period as well as during the entire 31-d breeding period. The PGF2alpha, and
      CIDR+PGF2alpha but not the control treatments were evaluated in dairy heifers
      (Exp. 3). The CIDR+PGF2alpha-treated heifers had a greater incidence of estrus
      (84%) during the first 3 d of the breeding period compared with the PGF2alpha
      treated heifers (57%), but pregnancy rates during the first 3 d or during the 31
      d breeding period were not improved for CIDR+PGF2alpha compared with PGF2alpha
      treated heifers. In summary, the concurrent treatment of CIDR and PGF2alpha
      improved synchronization rates relative to PGF2alpha alone or control. Improved
      estrus synchrony led to greater pregnancy rates for beef cows and beef heifers
      but failed to improve pregnancy rates for dairy heifers.

PMID- 11325207
TI  - The chemotactic properties of porcine seminal components toward neutrophils in
      vitro.
AB  - Our objectives were to investigate the mechanisms of postbreeding inflammation in
      swine by examining the chemotactic properties of polymorphonuclear neutrophilic
      granulocytes (PMN) and of various populations of spermatozoa and seminal plasma.
      Epididymal spermatozoa from two boars obtained under sterile conditions, washed
      ejaculated spermatozoa from two boars, and pooled seminal plasma from eight boars
      of known fertility were examined for chemotaxis to PMN. The chemotaxis of blood
      derived PMN in response to sperm and seminal plasma was evaluated and expressed
      as a percentage of a positive control (lipopolysaccharide-activated blood
      plasma). The mean chemotactic effect of washed sperm alone (4.4+/-0.04) and of
      epididymal sperm alone (3.4+/-0.06) was not different from that of the negative
      controls (3.1+/-0.05) of McCoy's medium with 10% heat-inactivated fetal calf
      serum. A marked chemotactic effect was detected when washed ejaculated and
      epididymal sperm were incubated with blood plasma, compared with blood plasma
      without spermatozoa (P < 0.001). Washed sperm in blood plasma (86.2+/-5.6) and
      epididymal sperm in blood plasma (83.9+/-7.7) were different from blood plasma
      alone (11.2+/-1.5), but no differences were detected between the two populations
      of sperm. This effect, however, was not completely inhibited by heat inactivation
      of the blood plasma. The chemotactic response of washed ejaculated and epididymal
      spermatozoa incubated in lipopolysaccharide-treated, heat-inactivated blood
      plasma were greater than that of the negative control (P < 0.05).
      Polymorphonuclear neutrophilic granulocyte migration toward seminal plasma was
      similar to the negative control (4.0+/-0.04 vs 3.1+/-0.05). It seems that porcine
      epididymal sperm and ejaculated sperm activate chemotactic components in porcine
      blood plasma and heat-inactivated blood plasma, suggesting that, at least
      partially, a heat-stable (noncomplement) blood plasma component may be involved
      in sperm-induced PMN chemotaxis. In contrast, porcine seminal plasma was not
      chemotactic to PMN. These results support the hypothesis that spermatozoa play an
      active role in initiating postbreeding endometritis.

PMID- 11325208
TI  - Impotence-free hormonal treatment of prostate cancer.
AB  - Since the protein-specific antigen (PSA) test is systematically used in some
      countries for cancer detection, many asymptomatic and latent cancer patients are
      uselessly victims of anxiety, hormonotherapy, and impotence, when they are not
      demolished by surgery and/or radiotherapy's local and/or regional complications.
      We propose to conduct a study of dexamethasone as treatment of such latent, small
      and even wrongly diagnosed cases. Certainly it exerts at small doses a discrete
      hormonal effect. But it has an anti-growth factor effect, which may explain its
      often beneficial action on prostate cancer with resistance to androgen
      inhibitors.

PMID- 11325209
TI  - Detection of prostate cancer by prostate-specific antigen.
AB  - The use of prostate-specific antigen (PSA) for early detection of prostate cancer
      has dramatically increased the reported incidence of this malignancy but its net
      benefit is unclear and remains controversial at present. Although several
      countries have adopted prostate cancer screening as a health policy, a reduction
      of cancer mortality would be an ultimate indication of the effectiveness of early
      detection. Since screening upon patient request cannot be refused, appropriate
      information should be provided until further support is available.

PMID- 11325210
TI  - Incidence rate and management of prostate carcinoma.
AB  - The age-standardised incidence of prostate cancer varies more than one
      hundredfold between the areas with the highest and lowest incidences in the
      world. In certain areas, in particular the Western countries, the incidence has
      increased rapidly over the last 20 years. There are several environmental and
      genetic factors which partly explain these variations, although the incidence
      probably depends most of all on the extent to which small latent tumours are
      detected. As the clinical significance of small tumours is uncertain, the value
      of early diagnosis and early aggressive treatment is controversial. Randomised
      trials addressing this question have been initiated and will hopefully provide
      more evidence-based data in a decade from now. Small localised tumours are
      managed by radical surgery or radiation therapy. In elderly men or men unfit for
      operation or radiation therapy surveillance is often preferred. For advanced or
      metastatic prostate cancers androgen deprivation has been the mainstay of
      treatment since the early 1940s. Recently, several new treatment strategies have
      evolved but have not yet been introduced into clinical routine.

PMID- 11325211
TI  - Acute myocardial infarction after transurethral resection of the prostate.
AB  - Several factors inherent in the transurethal resection of the prostate (TURP)
      procedure may impose stress on the cardiovascular system. The risk of acute
      myocardial infarction (AMI) is usually considered to be low but has still been an
      issue during the last 10 years. Interestingly, the concerns are focused on a
      possible adverse effect of TURP on the long-term risk of AMI and on survival.
      Selection bias has been a problem in many of the published studies, however. Co
      morbidity is also difficult to handle when the follow-up lasts for several years,
      in particular since benign prostatic enlargement alone seems to be associated
      with an increased risk of cardiovascular disease.

PMID- 11325212
TI  - Gene therapy in heart disease.
AB  - Application of gene therapy to the field of cardiovascular disorders has been the
      subject of intensive work over the recent period. Gene therapy for cardiovascular
      disorders is now fast developing with most therapies being devoted to the
      consequences (ischemia) rather than the causes of atherosclerotic diseases.
      Recent human clinical trials have shown that injection of naked DNA encoding
      vascular endothelial growth factor promotes collateral vessel development in
      patients with critical limb ischemia or chronic myocardial ischemia. Promising
      studies in animals have also fueled enthusiasm for treatment of human restenosis
      by gene therapy, but clinical applications are warranted. Application of gene
      transfer to other cardiovascular diseases will require the coordinated
      development of a variety of new technologies, as well as a better definition of
      cellular and gene targets.

PMID- 11325213
TI  - Plasma fatty acid status in Moroccan children: increased lipid peroxidation and
      impaired polyunsaturated fatty acid metabolism in protein-calorie malnutrition.
AB  - In previous studies on plasma fatty acid and antioxidant status in 29
      malnourished Moroccan children (12 with mild protein-calorie malnutrition, 17
      with severe protein-calorie malnutrition) compared to 15 healthy control children
      from the same area, we pointed out that these populations were heterogeneous in
      terms of their essential fatty acid and antioxidant status. The aim of the
      present study was to classify the children using the Waterlow classification and
      their essential fatty acid status. The discrepancies in lipid parameters,
      nutritional and inflammatory markers, blood oxidative indexes, antioxidant
      micronutrients or trace elements (selenium, zinc, vitamin E) related to
      polyunsaturated fatty acids were checked in these populations. Eight of the
      control subjects and nine of the severe protein-calorie malnutrition children
      were essential fatty acid-deficient, compared to only one of the mild protein
      calorie malnutrition group. Examination of the essential fatty acid-sufficient
      subjects with mild protein-calorie malnutrition, compared to the essential fatty
      acid-sufficient control subjects, showed only a decrease in Z scores and a non
      significant decrease in selenium and vitamin E. In severely malnourished
      children, albumin, cholesterol and low density lipoprotein (LDL) cholesterol,
      plasma selenium, vitamin E and zinc were low, whereas inflammatory proteins and
      triglycerides were high. These features worsened with essential fatty acid
      deficiency. In all protein-calorie malnutrition subjects, there was oxidative
      stress (increase in thiobarbituric-acid reactants, imbalance between plasma
      polyunsaturated fatty acid, vitamin E and selenium levels), even in the absence
      of essential fatty acid deficiency. Monounsaturated fatty acids, oleic
      acid/stearic acid (C18:1 n-9/C18:0) delta9 desaturase and n-3 and n-6 elongase
      activity indexes increased. The C18:1/C18:0 delta9 desaturase activity index was
      negatively correlated to Z scores (r = -0.44, P< 0.01 for Z score weight, r = 
      0.39, P < 0.01 for Z score height), albumin (r = -0.82, P < 0.01) and zinc (r = 
      0.51, P< 0.01) levels. In essential fatty acid-deficient, severe protein-calorie
      malnutrition subjects, delta6 desaturase activity was impaired, and there was a
      non-significant decrease in arachidonic acid. Essential fatty acid deficiency is
      a type of malnutrition, and is associated with an aggravation of all parameters
      in severe protein-calorie malnutrition. The increase in the C18:1/C18:0 delta9
      desaturase activity and enhanced lipid peroxidation without any essential fatty
      acid deficiency could be early markers of protein-calorie malnutrition.

PMID- 11325214
TI  - Oxygen toxicity: simultaneous measure of pentane and malondialdehyde in humans
      exposed to hyperoxia.
AB  - In order to estimate cell damage caused by free radicals during oxygenotherapy,
      we investigated the time course of two markers of lipoperoxidation: pentane in
      breath and malondialdehyde (MDA) in blood during brief normobaric hyperoxia. Nine
      healthy subjects inhaled hydrocarbon-free air (HCFA) for 30 minutes, hydrocarbon
      free 100% O2 (HCFO2) for 125 minutes and then HCFA for 70 minutes. After 15
      minutes of washout with HCFA, ambient pentane was eliminated. After HCFO2, at
      T175 versus T30 (i.e., 145 min from the start of 100% HCFO2), pentane production
      increased (P< 0.05). MDA rose significantly at T155 min (i.e., 125 min from the
      start of HCFO2), versus T30 (P< 0.01). These results suggest that acute hyperoxia
      causes a moderate increase in lipid peroxidation in healthy subjects. The
      increase of pentane and MDA confirms that acute hyperoxia induces lipid
      peroxidation in healthy subjects.

PMID- 11325215
TI  - Hyperthermia-induced cell death by apoptosis in myeloma cells.
AB  - We have analyzed by morphological (TEM) and histochemical (TUNEL reaction)
      criteria the type of cell death occurring in one case of human multiple myeloma
      after hyperthermia. Samples of cells examined immediately at the end of two
      treatments with a 15-day interval showed a significant degeneration, mostly
      demonstrating features of apoptosis (cell shrinkage, DNA fragmentation,
      karyorrhexis). The possible causes of the lag period between heating and
      apoptosis onset-expression are discussed.

PMID- 11325216
TI  - New acyclic sesquiterpenes and norsesquiterpenes from the Caribbean Gorgonian
      Plexaurella grisea.
AB  - The gorgonian Plexaurella grisea from Punta Cana, Dominican Republic, contains
      five new acyclic sesquiterpenes, (3E,5E)-3,7,11-trimethyl-9-oxododeca-1,3,5
      triene (3), (3Z,5E)-3,7,11-trimethyl-9-oxododeca-1,3,5-triene (4), (3E)-6-acetoxy
      3,11-dimethyl-7-methylidendodeca-1,3,10-triene (5), (3E,5E)-7-hydroxy-3,7,11
      trimethyldodeca-1,3,5,10-tetraene (6), and (3E,5E,9E)-8,11-diacetoxy-3,7,11
      trimethyldodeca-1,3,5,9-tetraene (7), and two new linear norsesquiterpenes,
      (2E,4E,7Z)-2,6,10-trimethylundeca-2,4,7,9-tetraenal (8) and (2E,4E)-2,6,10
      trimethylundeca-2,4,9-trienal (9), in addition to the known compounds 1, 2, and
      10. The structures of the new compounds 3-9 were elucidated by interpretation of
      spectroscopic data. In general, the new compounds are mildly cytotoxic against
      tumor cell lines, and although norsesquiterpene 8 was inactive, norsesquiterpene
      9 exhibited the greatest and selective activity against the P-388 tumor cell
      line.

PMID- 11325217
TI  - A formal total synthesis of racemic sesquiterpenoid sativene.
AB  - Several key reactions involving intramolecular cyclization, Grignard reaction,
      and ionic hydrogenation have been employed in a formal synthesis of sativene. The
      synthesis affords 3-isopropyl-6-methyltricyclo[4.4.0.0(2,8)]decan-7-one, 12,
      McMurry's penultimate precursor to sativene, in 28% overall yield in eight steps
      starting with the commercially available racemic Wieland--Miescher ketone.

PMID- 11325218
TI  - New allo-cedrane type sesquiterpene hemiketals and further sesquiterpene lactones
      from fruits of Illicium floridanum.
AB  - Three new tetracyclic sesquiterpene hemiketals possessing the very rare allo
      cedrane carbon skeleton, debenzoyl-7-deoxo-1 alpha,7 alpha-dihydroxytashironin,
      debenzoyl-7-deoxo-7 alpha-hydroxytashironin, and debenzoyl-7-deoxo-7 alpha
      hydroxy-3-oxotashironin (1--3), were isolated from the fruits of Illicium
      floridanum ELLIS (American Star Anise, Star bush). Their structures were
      elucidated by mass and NMR spectroscopic analyses. The molecular structure of 1,
      including absolute stereochemistry, was determined by single-crystal X-ray
      diffraction of its monohydrate. Only one compound of this type, tashironin, has
      previously been isolated from Illicium tashiroi. Furthermore, a new sesquiterpene
      lactone of the seco-prezizaane type, 3,4-anhydro-13,14-dihydroxyfloridanolide
      (4), and the known anislactone B (5) were isolated. The occurrence of further
      allo-cedrane sesquiterpenes in another Illicium species confirms the hypothesis
      of previous authors that this type of compound is a biogenetic precursor of the
      typical seco-prezizaane sesquiterpene lactones found in this genus. Moreover,
      regarding their co-occurrence with anislactone B as reported here, they may also
      be considered precursors for the anislactone skeletal type.

PMID- 11325219
TI  - New insecticidal rocaglamide derivatives and related compounds from Aglaia
      oligophylla.
AB  - Organic-soluble extracts of the twigs of Aglaia oligophylla collected in Vietnam
      yielded four insecticidal cyclopentatetrahydrobenzofurans of the rocaglamide type
      including one new natural product (compound 4). Moreover, two
      cyclopentatetrahydrobenzopyran derivatives, belonging to the aglain and
      aglaforbesin types, respectively, were also isolated. The aglaforbesin derivative
      6 proved likewise to be a new natural product. All isolated rocaglamide, aglain,
      and aglaforbesin derivatives have a characteristic methylenedioxy substituent
      linked to C-6 and C-7 or to C-7 and C-8, respectively. Structure elucidation of
      the new natural products and the determination of the absolute configuration of
      compound 1 by calculation of its CD spectrum with molecular dynamics simulation
      are described. All isolated rocaglamide derivatives exhibited strong insecticidal
      activity toward neonate larvae of the polyphageous pest insect Spodoptera
      littoralis when incorporated into an artificial diet, with LC(50) values varying
      between 2.15 and 6.52 ppm.

PMID- 11325220
TI  - Structure of alkaloid 275A, a novel 1-azabicyclo[5.3.0]decane from a dendrobatid
      frog, Dendrobates lehmanni: synthesis of the tetrahydrodiastereomers.
AB  - The principal alkaloid 275A in skins of the Colombian poison frog Dendrobates
      lehmanni has been identified as the pyrrolo[1,2-a]azepane (1), the first
      occurrence in nature of this "izidine" system. Tetrahydro-1 proved identical to
      one of the four synthetic diastereomers, 2a--2d, thereby establishing that 1 has
      the 5Z,10E relative stereochemistry. Alkaloid 1 is often accompanied by other
      congeners, in particular a 5Z,10Z diastereomer 15, a dihydro analogue 16, and a
      ketone 17. Such izidines in frogs may arise from dietary ants, as do other
      classes of izidines.

PMID- 11325221
TI  - Structure and neurotrophic activity of seco-prezizaane-type sesquiterpenes from
      Illicium merrillianum.
AB  - An extract of the pericarps of Illicium merrillianum has yielded four new
      sesquiterpenes: 3 alpha-hydroxycycloparvifloralone (1), 1,2
      dehydrocycloparvifloralone (2), (11) 7,14-ortholactone-3 alpha
      hydroxyfloridanolide (3), and 11-O-debenzoyltashironin (4) along with
      cycloparvifloralone (5), merrillianone (6), and tashironin (7). The structures of
      1--4 were determined on the basis of spectroscopic analyses. 11-O
      Debenzoyltashironin (4) showed neurotrophic activity in primary culture of rat
      cortical neurons at 0.1--10 microM. However, cycloparvifloralone-type
      sesquiterpenes (1, 2, 5, and 6) and tashironin (7) had no neurotrophic activity
      at these concentrations.

PMID- 11325222
TI  - New modified eremophilanes from the roots of Psacalium radulifolium.
AB  - The investigation of the chemical constituents from the roots of Psacalium
      radulifolium, a member of the matarique complex of medicinal plants, which
      includes several members of the Asteraceae, resulted in the isolation of four new
      modified eremophilanes: radulifolin A (4), epi-radulifolin A (5), radulifolin B
      (6), and radulifolin C (7), together with the known natural substances cacalol,
      cacalone, epi-cacalone, O-methyl-1,2-dehydrocacalol, adenostin A, decompostin,
      and neoadenostylone. Antimicrobial evaluation of the extracts and the isolated
      compounds indicated that cacalol was the major active compound.

PMID- 11325223
TI  - New peroxy triterpenes from the aerial roots of Ficus microcarpa.
AB  - Six new triterpenes, 3 beta-acetoxy-12 beta,13 beta-epoxy-11 alpha
      hydroperoxyursane (1), 3 beta-acetoxy-11 alpha-hydroperoxy-13 alpha H-ursan-12
      one (2), 3 beta-acetoxy-1 beta,11 alpha-epidioxy-12-ursene (3), (20S)-3 beta
      acetoxylupan-29-oic acid (4), (20S)-3 beta-acetoxy-20-hydroperoxy-30-norlupane
      (5), and 3 beta-acetoxy-18 alpha-hydroperoxy-12-oleanen-11-one (6), together with
      3 beta-acetoxy-12-oleanen-11-one (7), were isolated from the aerial roots of
      Ficus microcarpa. Compounds 1-3, 5, and 6 were characterized as new
      peroxytriterpenes. The structures of 3 and 6 were confirmed by X-ray
      crystallography, and their structures were elucidated by spectroscopic and
      chemical methods.

PMID- 11325224
TI  - A cyanoallyl glucoside from Alliaria petiolata, as a feeding deterrent for larvae
      of Pieris napi oleracea.
AB  - Alliarinoside, a feeding inhibitor against early instar larvae of Pieris napi
      oleracea, was isolated from the foliage of Alliaria petiolata and characterized
      as (2Z)-4-(beta-D-glucopyranosyloxy)-2-butenenitrile (1) by spectroscopic
      methods. The structural assignment was confirmed by synthesis of peracetylated
      alliarinoside (2) and its 2E isomer (3). A sample of synthetic 1 was isolated by
      preparative HPLC from the hydrolysis of the 2Z acetate. Feeding inhibition assays
      showed comparable activity for the synthetic and natural glycosides.

PMID- 11325225
TI  - Cloning, sequencing, and heterologous expression of the elmGHIJ genes involved in
      the biosynthesis of the polyketide antibiotic elloramycin from Streptomyces
      olivaceus Tu2353.
AB  - Elloramycin A (1) belongs to a small family of naphthacenequinones characterized
      by a unique highly hydroxylated cyclohexenone moiety. A cosmid clone 16F4,
      harboring genes for the production of 1 from Streptomyces olivaceus Tu2353, has
      been previously isolated. DNA sequence analysis of a 3.2-kb fragment from 16F4
      revealed four open reading frames--the elmGHIJ genes. Heterologous expressions of
      the elmGHI genes in either Escherichia coli or Streptomyces lividans, followed by
      biochemical characterizations of the ElmGHI proteins, established ElmG as
      tetracenomycin B2 oxygenase, ElmH as tetracenomycin F1 monooxygenase, and ElmI as
      tetracenomycin F2 cyclase. These results provide direct biochemical evidence for
      the hypothesis that the biosynthesis of 1 in S. olivaceus parallels that of
      tetracenomycin C (2) in Streptomyces glaucescens and support the notion that the
      biosynthesis of the highly hydroxylated cyclohexenone moiety in other polyketides
      most likely follows the same paradigm as the tetracenomycin B2 or A2 oxygenase.

PMID- 11325226
TI  - New taxane analogues from the needles of Taxus canadensis.
AB  - Eight minor taxanes have been identified for the first time in Taxus canadensis
      needles. Four of these metabolites are new taxane analogues: 7-acetyl-10
      deacetyltaxol (1), 2'-acetyl-7-epi-cephalomannine (2), 10-deacetyl-10-oxo-7-epi
      cephalomannine (3), and 10-acetylglycollylbaccatin VI (4).

PMID- 11325227
TI  - Triterpene saponins from Vietnamese ginseng (Panax vietnamensis) and their
      hepatocytoprotective activity.
AB  - The methanol extract of Vietnamese ginseng (Panax vietnamensis) was found to
      possess hepatocytoprotective effects on D-galactosamine (D-GalN)/tumor necrosis
      factor-alpha (TNF-alpha)-induced cell death in primary cultured mouse
      hepatocytes. Further chemical investigation of the extract afforded two new
      dammarane-type triterpene saponins, ginsenoside Rh(5) (1) and vina-ginsenoside
      R(25) (2), as well as eight known dammarane-type triterpene saponins, majonoside
      R(2) (3), pseudo-ginsenoside RT(4) (4), vina-ginsenosides R(1) (5), R(2) (6), and
      R(10) (7), ginsenosides Rg(1) (8), Rh(1) (9), and Rh(4) (10), and a known
      sapogenin protopanaxatriol oxide II (11). Their structures were elucidated on the
      basis of spectral analysis. In addition, by the using LC-electrospray ionization
      (ESI)-MS method, five known saponins, ginsenosides Rb(1), Rb(2), Rc, Rd, and Re
      (12--16), were also identified in the extract. Among the compounds isolated,
      majonoside R(2) (3), the main saponin in Vietnamese ginseng, showed strong
      protective activity against D-GalN/TNF-alpha-induced cell death in primary
      cultured mouse hepatocytes. This demonstrates that the hepatocytoprotective
      effect of Vietnamese ginseng is due to dammarane-type triterpene saponins that
      have an ocotillol-type side chain, a characteristic constituent of Vietnamese
      ginseng.

PMID- 11325228
TI  - Hydroxylations and methylations of quercetin, fisetin, and catechin by
      Streptomyces griseus.
AB  - Preparative-scale biotransformation of quercetin (1), fisetin (7), and (+)
      catechin (12) with Streptomyces griseus (ATCC 13273) resulted in the isolation
      and characterization of nine known hydroxylated and/or methylated (2--6, 8, 9,
      11, 13a) metabolites and two previously unknown (10 and 14) metabolites.
      S.griseus catalyzed aromatic hydroxylations of rings A and B of quercetin and
      fisetin. Mono- and dimethoxy ring-B metabolites were obtained with all three
      substrates. Methylation appeared to occur only when catechol functional groups
      were present. Metabolite structures were established by FABMS, EIMS, and 1D and
      2D NMR analysis.

PMID- 11325229
TI  - Sesquiterpenes and monoterpenes from the bark of Inula macrophylla.
AB  - Eleven new sesquiterpenes (1--11) and two thymol derivatives (12, 13), along with
      12 known sesquiterpenes and monoterpenes, were isolated from the bark of Inula
      macrophylla. Their structures were determined on the basis of spectral evidence
      (especially by HREIMS and 2D NMR) as well as chemical transformations. The
      structure of macrophyllic acid A (1) was confirmed by X-ray analysis, and the
      absolute configuration of 1 was determined on the basis of the appropriate
      chemical conversions and the application of a modified Mosher's method.

PMID- 11325230
TI  - Synthesis of (7S,15S)- and (7R,15S)-dolatrienoic acid.
AB  - The stereospecific synthesis of (7S,15S)- and (7R,15S)-dolatrienoic acids (2) was
      achieved using an approach consisting of 16 linear steps. The C-11--C-16 unit was
      prepared in seven steps from ethyl (S)-lactate and coupled using a trans
      selective Wittig--Schlosser reaction to the C-7--C-10 fragment. Chirality at the
      C-7 position was introduced using an Evan's-type chiral auxiliary in a cobalt
      mediated Reformatsky reaction to give the (3S,11S)-aldehyde 24. Subsequent Wittig
      reaction with a phosphonium salt derived in three steps from tiglic acid gave
      (7S,15S)-dolatrienoic acid, one of the four possible diastereoisomers of the
      nonpeptide portion of the strong cancer cell growth inhibitory cyclodepsipeptide
      dolastatin 14 (1). A second diastereoisomer, (7R,15S)-dolatrienoic acid, was
      synthesized employing chiral oxazolidinone 21 by an analogous synthetic route.

PMID- 11325231
TI  - Specific antioxidant activity of caffeoyl derivatives and other natural phenolic
      compounds: LDL protection against oxidation and decrease in the proinflammatory
      lysophosphatidylcholine production.
AB  - Specific antioxidant activity (SAA) (i.e., activity related to the molar or
      gallic acid equivalent amount of antioxidant) of natural polyphenolic mixtures or
      pure phenolic compounds was studied using their capacity to delay the conjugated
      diene production brought about by in vitro LDL copper-mediated or AAPH-mediated
      oxidation. The cinnamic acid series (caffeic, sinapic, ferulic acids) displayed a
      constant SAA over a large range of concentrations, whereas the benzoic acid
      series (gallic and protocatechuic acids) showed much higher SAA at low
      concentrations. The natural phenolic mixtures had a constant SAA. The highest SAA
      was obtained with caffeoyl esters (caffeoylquinic, rosmarinic, and
      caffeoyltartaric acids) and catechin for the copper-oxidation and the AAPH
      oxidation system, respectively. Phenolic mixtures and acids delayed vitamin E
      depletion and decreased proinflammatory lysophosphatidylcholine production. As
      with polyphenols, probucol delayed lysophosphatidylcholine and conjugated dienes
      production, at higher concentrations, but was not effective at preventing vitamin
      E depletion. Polyphenols prevent the oxidation of LDL and its constituents
      (vitamin E, phosphatidylcholine), which is compatible with an antiinflammatory
      and antiatherosclerotic role in pathophysiological conditions.

PMID- 11325232
TI  - Schizanrins [corrected] B, C, D, and E, four new lignans from Kadsura matsudai
      and their antihepatitis activities.
AB  - Bioassay-directed fractionation of ethanolic extract of Kadsura matsudai Hayata
      has resulted in the isolation of four novel C(18) dibenzocyclooctadiene lignans,
      schizanrin B (1), schizanrin C (2), schizanrin D (3), and schizanrin E (4).
      Schizanrin B (1) showed moderate to strong activity for antihepatitis in both
      anti-HBsAg and anti-HBeAg assays, and 3 and 4 also were active in the latter
      assay [corrected]. Compounds 1--4 were inactive in vitro against HIV replication
      in H9 lymphocytes. All new structures were elucidated using spectral analysis.
      Their structural elucidation by spectral and structure--activity relationships is
      also discussed.

PMID- 11325233
TI  - Blepharocalyxins C--E, three new dimeric diarylheptanoids, and related compounds
      from the seeds of Alpinia blepharocalyx.
AB  - Three novel diarylheptanoids, blepharocalyxins C--E (5--7), together with four
      new (1--4) and one known (8) diarylheptanoids bearing a tetrahydropyran ring were
      isolated from the residual fraction of an EtOH extract of the seeds of Alpinia
      blepharocalyx. The structures and the stereochemistry at the chiral centers of
      the new diarylheptanoids were elucidated by spectroscopic techniques including 2D
      NMR spectroscopy. Blepharocalyxins C--E (5--7) have a novel carbon framework and
      are dimeric diarylheptanoids consisting of two diarylheptanoid units.
      Blepharocalyxin D (6) showed potent antiproliferative activity against murine
      colon 26-L5 carcinoma cells (ED(50), 3.61 microM), while against human HT-1080
      fibrosarcoma cells, blepharocalyxin E (7) showed potent activity (ED(50), 9.02
      microM).

PMID- 11325234
TI  - Bioactive constituents of the roots of Licania intrapetiolaris.
AB  - Fractionation of a methanol extract of the roots of Licania intrapetiolaris, as
      directed by activity against the KB assay, has led to the isolation of two novel
      clerodane diterpenoids, intrapetacins A (1) and B (2), and the known triterpenoid
      cucurbitacin B (3). The structures of 1 and 2 were deduced from one- and two
      dimensional NMR experiments, including relative stereochemical assignments based
      on NOESY correlations and COSY coupling constants. Compound 3 was the most potent
      against the KB assay, but both 1 and 2 displayed moderate cytotoxicity. When
      evaluated against an antifungal assay using Aspergillus niger, 2 caused a
      significant zone of inhibition of fungal growth, while 1 was completely inactive.
      To the best of our knowledge, this is the first report of the isolation of
      bioactive compounds from the genus Licania.

PMID- 11325235
TI  - Annomolin and annocherimolin, new cytotoxic annonaceous acetogenins from Annona
      cherimolia seeds.
AB  - Two new cytotoxic annonaceous acetogenins, annomolin (1) and annocherimolin (2),
      were isolated from an ethanolic extract of the seeds of Annona cherimolia.
      Annomolin has a mono-THF ring with one flanking hydroxyl and possesses a 1,2-diol
      at C-7/8 of the aliphatic chain. Annocherimolin has a mono-THF ring with two
      flanking hydroxyls and possesses a double bond at C-21/22. Their structures were
      elucidated by spectral data and chemical derivatization. Compound 1 showed
      cytotoxic selectivity for the human prostate tumor cell line (PC-3), with a
      potency of over 10,000 times that of adriamycin. Compound 2 showed cytotoxic
      potencies about 10,000 times those of adriamycin in the breast (MCF-7) and colon
      (HT-29) cancer cell lines.

PMID- 11325236
TI  - Salmoxanthin, deepoxysalmoxanthin, and 7,8-didehydrodeepoxysalmoxanthin from the
      Salmon Oncorhynchus keta.
AB  - The absolute configuration of salmoxanthin (5,6-epoxy-5,6-dihydro-beta,epsilon
      carotene-3,3',6'-triol) (1) first isolated from the salmon Oncorhynchus keta was
      determined to be 3S, 5R, 6S, 3'S, 6'R. Furthermore, two minor carotenoids,
      deepoxysalmoxanthin (2) and 7,8-didehydrodeepoxysalmoxanthin (3), were isolated,
      and their structures were determined to be (3R,3'S,6'R)-beta,epsilon-carotene
      3,3',6'-triol and (3R,3'S,6'R)-7,8-didehydro-beta,epsilon-carotene-3,3',6'-triol
      by (1)H NMR and CD spectroscopy.

PMID- 11325237
TI  - Diterpenoids from the leaves of Juniperus chinensis var. kaizuka.
AB  - Two diterpenoids based on novel carbon skeletons, namely, 8,19-dioxo-8,14-seco
      chinan-14,11-olide (1) and 8-oxo-8,14-seco-abiet-12-en-14,19-dial (2), have been
      isolated, together with two new abietane diterpenoids, 13 beta,14 beta-epoxyabiet
      7-en-19,6 beta-olide (3) and 7 beta-hydroxyabieta-8,11,13-trien-19-al (4), from
      the leaves of Juniperus chinensis. Their structures were determined by
      spectroscopic methods, including 2D NMR, and, in the case of 1, X-ray
      crystallographic analysis.

PMID- 11325238
TI  - New constituents of the leaves of Alpinia flabellata.
AB  - Two new compounds were isolated from the leaves of Alpinia flabellata. The
      structures of these compounds were determined by a combination of NMR techniques
      and HREIMS as 4-hydroxy-2-(2,4,5-trimethoxyphenyl)-2E-butenal (1) and rel-labd-12
      en-15(16)-olid-7-one-8R-spiro-1'-[2S-(2,4,5-trimethoxyphenyl)-3-cyclohexene] (2).

PMID- 11325239
TI  - Cacalolides from Senecio madagascariensis.
AB  - 14-Isovaleryloxy-O-methyl-1,2-dehydrocacalol (1) and cycloart-23-ene-3,25-diol,
      beta-sitosterol, and stigmasterol, along with five new cacalolides, 1-hydroxy-2
      methoxy-1,2,3,4-dehydro-6-dehydroxycacalone (2), 1-hydroxy-2-methoxy-1,2,3,4
      dehydrocacalone (3), 1,2-dimethoxy-1,2,3,4-dehydro-6-dehydroxycacalone (4), 1,2
      dimethoxy-1,2,3,4-dehydrocacalone (5), and 2-methoxy-O-methyl-1-oxo-2,3
      dehydrocacalol (6), were isolated from Senecio madagascariensis collected from
      Colombia. The structures of the new compounds were determined using one- and two
      dimensional NMR techniques. In addition, the structure of 2 was corroborated by
      derivatizations and single-crystal X-ray diffraction studies.

PMID- 11325240
TI  - Antimalarial, antiviral, and antitoxoplasmosis norsesterterpene peroxide acids
      from the Red Sea sponge Diacarnus erythraeanus.
AB  - A new norsesterterpene acid, named muqubilone (1), along with the known
      sigmosceptrellin-B and muqubilin were isolated from the Red Sea sponge Diacarnus
      erythraeanus. The structure determination of 1 was based primarily on 1D and 2D
      NMR analyses. Sigmosceptrellin-B exhibits significant in vitro antimalarial
      activity against Plasmodium falciparum (D6 and W2 clones) with IC(50) values of
      1200 and 3400 ng/mL, respectively. Muqubilin and 1 show in vitro antiviral
      activity against herpes simplex type 1 (HSV-1) with ED(50) values of 7.5 and 30
      microg/mL, respectively. Muqubilin and sigmosceptrellin-B display potent in vitro
      activity against Toxoplasma gondii at a concentration of 0.1 microM without
      significant toxicity.

PMID- 11325241
TI  - Microxine, a new cdc2 kinase inhibitor from the Australian marine sponge
      Microxina species.
AB  - A new purine derivative microxine (1) was isolated from the Australian marine
      sponge Microxina sp. The compound was isolated via reversed-phase chromatography
      and its structure determined spectroscopically. Microxine was found to weakly
      inhibit cdc2 kinase activity with an IC(50) of 13 microM.

PMID- 11325242
TI  - New macrolides and furan carboxylic acid derivative from the sponge-derived
      fungus Cladosporium herbarum.
AB  - Bioassay-guided fractionation of organic extracts of Cladosporium herbarum,
      isolated from the marine sponge Callyspongia aerizusa, yielded two new macrolide
      metabolites: pandangolide 3 and 4 (1 and 2) and the known fungal metabolites
      pandangolide 2 (3), cladospolide B (4), and iso-cladospolide B (5). Also isolated
      were the antimicrobially active (against Bacillus subtilis and Staphylococcus
      aureus) furan carboxylic acids: Sumiki's acid (6) and its new derivative, acetyl
      Sumiki's acid (7). All structures were elucidated by spectroscopic methods.

PMID- 11325243
TI  - A new metabolite from the marine bacterium Vibrio angustum S14.
AB  - The new metabolite [1-(2'-methylpropoxy)-2-hydroxy-2-methylpropoxy]butane was
      isolated from the cell-free culture supernatant of the marine bacterium Vibrio
      angustum S14 as part of studies investigating the role of chemical signals in
      prokaryote--prokaryote and prokaryote--eukaryote interactions. The structure was
      elucidated by interpretation of its high-field NMR and mass spectrometric data.
      [1-(2'-Methylpropoxy)-2-hydroxy-2-methylpropoxy]butane induced the acylated
      homoserine lactone (AHL) reporter system in Agrobacterium tumefaciens and
      bioluminescence in Vibrio harveyi.

PMID- 11325244
TI  - Additional bioactive Lyso-PAF congeners from the sponge Spirastrella abata.
AB  - A known (1) and four new (2--5) lyso-PAF (platelet activating factor) derivatives
      were isolated from the sponge Spirastrella abata. Two of them are unprecedented
      in having a methoxy group at C-2'. The structures have been determined by
      combined spectroscopic methods. Their inhibitory effect on the biosynthesis of
      cholesterol and cytotoxicity against human solid tumor cell lines are reported.

PMID- 11325245
TI  - Two bioactive saponins from Albizia subdimidiata from the Suriname rainforest.
AB  - Bioassay-guided fractionation of a methanol extract of Albizia subdimidiata using
      the engineered yeast strains 1138, 1140, 1353, and Sc7 of Saccharomyces
      cerevisiae as the bioassay tool resulted in the isolation of the two active
      saponins 1 and 2; one of these, albiziatrioside A (1), is described for the first
      time. The structures of 1 and 2 were established on the basis of HRMS, 1D and 2D
      NMR spectral data, and GC--MS analysis of the sugar units. Both isolated
      compounds showed significant cytotoxicity against the A2780 cell line.

PMID- 11325246
TI  - New xenicane diterpenoids from the gorgonian Acalycigorgia inermis.
AB  - Eight diterpenes and norditerpenes including five new xenicane metabolites (4--8)
      have been isolated from the gorgonian Acalycigorgia inermis. The structures of
      these compounds have been determined by combined spectroscopic analysis. The new
      compounds exhibited significant cytotoxicity against a human leukemia cell-line.

PMID- 11325247
TI  - Prenostodione, a novel UV-absorbing metabolite from a natural bloom of the
      cyanobacterium Nostoc species.
AB  - A novel UV-absorbing natural product, prenostodione (1), has been isolated from a
      natural bloom of the cyanobacterium Nostoc sp. (TAU strain IL-235). Homonuclear
      and heteronuclear 2D NMR techniques as well as HREIMS determined the gross
      structure of 1.

PMID- 11325248
TI  - Anti-HIV prenylated flavonoids from Monotes africanus.
AB  - Six flavonoids, among them a new dihydroflavonol, 6,8-diprenylaromadendrin (1),
      and the flavonol 6,8-diprenylkaempferol (3), have been isolated from the organic
      extract of Monotes africanus. The isolated compounds containing a 5,7-dihydroxy
      6,8-diprenyl system in the A ring of the flavonoid (1, 3, and 6) exhibited HIV
      inhibitory activity in the XTT-based, whole-cell screen. In addition, several
      (13)C NMR assignments of lonchocarpol A (6) were corrected.

PMID- 11325250
TI  - Spirodienone derivatives of a spherand-type calixarene.
AB  - Oxidation of the spherand-type calixarene 4 with 1 or 2 equiv of
      phenyltrimethylammonium tribromide/base afforded mono- and bis(spirodienone)
      derivatives (8b and 9, respectively). The spirodienone groups are derived from
      the oxidation of two phenols connected by a common methylene group. NOESY data
      indicated that 9 possesses a "head to tail" arrangement of the spirodienone
      groups. Oxidation of 4 with 3 equiv of the oxidizing reagent afforded two
      tris(spirodienone) calixarene derivatives 11 and 10 with C(1) and C(3)
      symmetries, respectively. The same tris(spirodienone) products were obtained by
      oxidation of 9 with I(2)/aq KOH. Tris(spirodienone) 11 displayed NOE cross-peaks
      in the NOESY NMR spectrum consistent with a nonalternant disposition of carbonyl
      and ether groups. Upon heating 10 and 11 isomerize in the solid state and in
      solution. The major component in the equilibration mixtures is 11, indicating
      that this is the thermodynamically more stable tris(spirodienone) isomer.

PMID- 11325249
TI  - Antibacterial diterpenes from the roots of Salvia blepharochlaena.
AB  - The roots of Salvia blepharochlaena have yielded two new diterpenoids, blephaein
      (1) and O-methylpisiferic acid methyl ester (2), together with eight known
      diterpenoids. The structures of the new compounds were established by
      spectroscopic analysis and by some chemical reactions. Potent antibacterial
      activity was exhibited by the known compounds horminone (9) and 7-acetylhorminone
      (10) against Staphylococcus aureus ATCC 6538 P, Staphylococcus epidermidis ATCC
      12226, and Bacillus subtilis ATCC 6633. Horminone was also found to be active
      against Enterococcus faecalis ATCC 29212.

PMID- 11325251
TI  - Stereochemistry of a spherand-type calixarene.
AB  - The stereochemistry of the spherand-type calixarene 2a is analyzed in terms of
      the configuration of the three 2,2'-dihydroxybiphenyl subunits (R or S) and the
      disposition of the methylene groups (crown or twist). X-ray crystallography
      indicates that the neutral 2a and its mono- or dianion (in form of the salts 2a(
      ) x C(5)H(5)NH(+) and 2a(2)(-) x 2Et(3)NH(+)) exist essentially in the same
      conformation (RRS/SSR-twist). This asymmetric RRS/SSR-twist form is the lowest
      energy conformer according to molecular mechanics calculations. Low-temperature
      (1)H NMR data indicate the presence of a major conformer of C(1) symmetry, in
      agreement with a RRS/SSR-twist form. The lowest energy topomerization pathway
      mutually exchanges two pairs of methylene protons and is ascribed to an
      enantiomerization process involving rotation around an Ar-Ar bond.

PMID- 11325252
TI  - Gitonic and distonic alkanonium dications (diprotonated alkane dications
      C(n)H(2n+4(2+)), n = 1-4)(1).
AB  - The structures and stabilities of gitonic and distonic alkanonium dications,
      i.e., diprotonated alkane dications C(n)H(2n+4)(2+) (n = 1-4), were investigated
      at the MP4(SDTQ)/6-311G**//MP2/6-31G** level. The global minimum energy
      structures (2, 4, 7, and 10) of the C(n)H(2n+4)(2+) dications are double C--H
      protonated alkanes to give structures with two two electron three-center (2e-3c)
      bonds. Two different dissociation pathways for the dications, viz deprotonation
      and demethylation, were also computed. Demethylation was found to be the
      favorable mode of dissociation.

PMID- 11325253
TI  - Photooxygenation of the helimers of (-)-isocolchicine: regio- and facial
      selectivity of the [4 + 2] cycloaddition with singlet oxygen and surprising
      endoperoxide transformations.
AB  - Photooxygenation of the helimeric mixture of (-)-(M,7S)/(P,7S)-isocolchicine (6)
      with the superdienophile singlet oxygen has been studied. Cycloaddition occurred
      with high regioselectivity at the 7a,11-positions of the alkaloid and
      predominantly at the diene face anti to the amidic substituent at the stereogenic
      center C-7, leading to two endoperoxides 7 (syn) and 8 (anti) with an 1:7 ratio.
      The structure of the minor product 7 was established by X-ray analysis.
      Investigation of the triethylamine induced transformation of the predominant
      endoperoxide 8 furnished a mixture of two isomers (M,7S)-10a/(M,7S)-10b in a 2:1
      ratio possibly with constitutional interconversion and with (M,7S)-9 as plausible
      intermediate. Treatment of this mixture with silica gel/ethyl acetate at ambient
      temperature surprisingly led to an atropenantiomerically pure colchicinoid (M,7S)
      12 characterized by an eightmembered oxocine B-ring, the structure and absolute
      configuration of which could be determined by X-ray analysis. For the
      unprecedented formation of the novel colchicinoid (M,7S)-12 a plausible reaction
      pathway is suggested, involving a complete transfer of the (M) helical asymmetry
      of the intermediate (M)-11 into (S) asymmetry of the newly formed carbon center
      of (M,7S)-12. Prerequisite for such a scenario is the configurational stability
      of the intermediate pseudobiaryl (M)-11, under the conditions employed, allowing
      to transmit the axial chirality onto the chiral center of the product (M,7S)-12.

PMID- 11325254
TI  - Electronic delocalization contribution to the anomeric effect evaluated by
      computational methods.
AB  - This study proposes the determination of the electronic delocalization
      contribution to the Anomeric Effect (EDCAE, Delta Delta E(deloc), eq 3) as a
      computational alternative in the evaluation of the excess of the axial preference
      shown by an electronegative substituent located at alpha position to the annular
      heteroatom of a heterocyclic compound (anomeric position) in both the presence
      and the absence of electronic delocalization retaining the same molecular
      geometry. The determination of the EDCAE is computationally accessible through
      the application of the natural bond orbital analysis (NBO). This type of analysis
      allows the comparison of hypothetical molecules lacking electronic delocalization
      (Lewis molecules, in which the electrons are strictly located in bonds and lone
      pairs) with the fully delocalized molecules retaining the same geometry and the
      evaluation of the anomeric effect in terms of eq 3. The role of the Lewis
      molecules is the same as the cyclohexane used experimentally to evaluate the
      anomeric effect. The advantage of doing this is that Lewis molecules are
      stereoelectronically inert. Applying this methology to cyclic and acyclic
      molecules at B3LYP/6-31G(d,p) and HF/6-31G(d,p)//B3LYP/6-31G(d,p) levels of
      theory, we found that the anomeric effect shown by Cl in 1,3-dioxane; F, Cl, SMe,
      PH(3), and CO(2)Me groups in 1,3-dithiane is of stereoelectronic nature while the
      preference of F, OMe, and NH(2) in 1,3-dioxane and the P(O)Me(2) group in 1,3
      dithiane is not. Furthermore, this methodology shows that anomeric effects
      without stereoelectronic origin can modify the molecular geometry in agreement
      with the geometric pattern required by the double-bond no-bond model, as recently
      proposed by Perrin.

PMID- 11325255
TI  - Rigorous interpretation of electronic density functions of axial and equatorial
      conformers of dimethylphosphinoylcyclohexane, 2-(dimethylphosphinoyl)-1,3,5
      trithiane, and 2-(dimethylphosphinoyl)-1,3-dithiane-1,1,3,3-tetraoxide.
AB  - Theoretical analysis within the frame of the Topological Theory of Atoms in
      Molecules confirms the repulsive steric interaction between an axial
      dimethylphosphinoyl group and the syn-diaxial hydrogens in cyclohexane derivative
      2-ax. In seemingly good agreement with experiment, equatorial isomer 2-eq was
      calculated to be 1.49 kcal/mol more stable than 2-ax. (Experimental energy
      difference in (diphenylphosphinoyl)cyclohexane, Delta H(o) = 1.96 kcal/mol.) In
      contrast, axial 2-(dimethylphosphinoyl)-1,3,5-trithiane, 3-ax, was calculated to
      be 6.38 kcal/mol more stable than 3-eq. (Experimentally, the axial conformer of 2
      (diphenylphosphinoyl)-1,3,5-trithiane, was found to be 1.43 kcal/mol more stable
      than the equatorial conformer, in solvent chloroform.) Theoretical analysis, in
      particular the electron density at the bond critical point within the C(4,6)
      H...O=P bonding trajectory, implies significant bonding in this segment of
      interacting atoms. By the same token, substantial positive charge is acquired by
      the C--H bonds adjacent to the sulfonyl groups in disulfone 4. Hydrogen bonding
      between the phosphoryl group and H(4,6) leads to stabilization of 4-ax, which is
      estimated to be 5.0 kcal/mol lower in energy than 4-eq. This conclusion is
      supported by examination of P==O...H--C(4,6) bond trajectories, as well as from
      evaluation of the critical point properties along those interacting moieties. By
      contrast, fluorinated derivative 5 is more stable in the equatorial conformation,
      indicating a repulsive electrostatic interaction of the C--F...O-P entity in 5
      ax.

PMID- 11325256
TI  - Synthesis of benzonorbornadienes: regioselective benzyne formation.
AB  - This report details the synthesis of several benzonorbornadienes by Diels--Alder
      cycloaddition of cyclopentadiene derivatives with substituted benzyne
      intermediates, which were generated by low-temperature metal--halogen exchange of
      halobenzenes. General conditions were developed, allowing synthesis of most
      benzonorbornadienes described herein at the multigram scale with isolated yields
      approaching 90% in some cases. Cycloaddition of the benzyne produced by
      substitution of a chlorodifluorobenzene for a bromodifluorobenzene in the metal-
      halogen exchange reaction unexpectedly gave a different benzonorbornadiene. The
      benzyne, which resulted by a deprotonation pathway rather than by metal-halogen
      exchange, formed in a highly regioselective elimination step.

PMID- 11325257
TI  - 2'-Ribose-ferrocene oligonucleotides for electronic detection of nucleic acids.
AB  - We have synthesized two novel phosphoramidites with a ferrocenyl moiety at the 2'
      ribose position linked through a butoxy linker. Using automated DNA/RNA synthesis
      techniques, oligonucleotides containing ferrocene at various positions were
      prepared and characterized by HPLC, MALDI-TOF mass spectrometry, and
      electrochemistry. Thermal stability studies of the ferrocene-modified DNA
      duplexes revealed that introduction of one or two ferrocenyl complexes does not
      result in an observed change of the T(m) values of the corresponding DNA duplexes
      when compared to the nonmodified hybrids. These data indicate that the
      introduction of a ferrocenyl group at the 2'-position of the ribose ring
      containing either a purine or pyrimidine base has no effect on the stability of
      the modified DNA. The electrochemical behavior of the ferrocene-containing DNA
      was examined by cyclic voltammetry. The modified 2'-ferrocene-oligonucleotides
      are electrochemically active and can be used as signaling probes for the
      electronic detection of nucleic acids on bioelectronic sensors.

PMID- 11325258
TI  - Flash vacuum pyrolysis over solid catalysts. 1. Pyrazoles over zeolites.
AB  - Flash vacuum pyrolysis (fvp) reactions of 1H-pyrazole (1), 3,5-dimethylpyrazole
      (2), and 3,5-diphenylpyrazole (3) were carried out over zeolites. Reactions were
      performed using ZCOY-7, NH(4)-Y, and Na-Y zeolites. Reaction temperatures of
      heterogeneous reactions were lower than the corresponding temperatures in the
      homogeneous system, showing a catalytic effect of the zeolites. Compounds 1-3
      afforded nitrogen extrusion in homogeneous fvp reactions while in the
      heterogeneous ones different reactions were present. Compounds 1 and 2 also
      afforded nitrogen extrusion; products arising from ring fragmentation were found
      in reactions of 2 and 3 while an isomeric imidazole was isolated in reactions of
      3. Isomerization of 3 is attributed to a transition-state selectivity by the
      catalyst due to the relation between the size of the molecule and the cavity of
      the zeolite. This isomerization reaction was present only when zeolites with
      active Bronsted sites were used.

PMID- 11325259
TI  - Chemoenzymatic synthesis of neoglycopeptides: application to an alpha-Gal
      terminated neoglycopeptide.
AB  - A novel methodology for the enzymatic preparation from suitably derivatized
      oligosaccharides of N-linked neoglycopeptides using the microbial glutaminyl
      peptide gamma-glutamyl transferase, transglutaminase (TGase), is described. N
      Allyl glycosides of various oligosaccharides were photochemically coupled with
      cysteamine to yield amino-terminated thioether spacers, which were accepted by
      transglutaminase to transamidate the side-chain gamma-carboxamide group in the
      dipeptide Z-Gln-Gly.

PMID- 11325260
TI  - Use of fluorobenzoyl protective groups in synthesis of glycopeptides: beta
      elimination of O-linked carbohydrates is suppressed.
AB  - Fluorobenzoyl groups have been investigated as alternatives to acetyl and benzoyl
      protective groups in carbohydrate and glycopeptide synthesis. D-Glucose and
      lactose were protected with different fluorobenzoyl groups and then converted
      into glycosyl bromides in high yields (>80% over two steps). Glycosylation of
      protected derivatives of serine with these donors gave 1,2-trans glycosides in
      good yields (approximately 60--70%) and excellent stereoselectivity without
      formation of ortho esters. The resulting glycosylated amino acid building blocks
      were then used in solid-phase synthesis of two model O-linked glycopeptides known
      to be unusually sensitive to beta-elimination on base-catalyzed deacylation. When
      either a 3-fluoro- or a 2,5-difluorobenzoyl group was used for protection of each
      of the two model glycopeptides the extent of beta-elimination decreased from 80%
      to 10% and from 50% to 0%, respectively, as compared to when using the ordinary
      benzoyl group. Fluorobenzoyl groups thus combine the advantages of the benzoyl
      group in formation of glycosidic bonds (i.e., high stereoselectivity and low
      levels of ortho ester formation) with the ease of removal characteristic of the
      acetyl group.

PMID- 11325261
TI  - Synthesis and characterization of photoswitchable lipids containing
      hemithioindigo chromophores.
AB  - The synthesis of four lipids containing the hemithioindigo chromophore as part of
      the fatty acid is described. Heck reaction of bromophenyl thioacetate esters with
      acrylonitrile, followed by reduction, ester hydrolysis, and Friedel--Craft
      acylation--cyclization gave a substituted thioindoxyl that condensed with an
      alkoxy benzaldehyde to produce the hemithioindigo. "Solventless" nitrile
      hydrolysis followed by mixed anhydride coupling of the acid with
      glycerophosphocholine produced lipids bearing two hemithioindigo chromophores.
      The photochemistry of various hemithioindigo derivatives was studied to confirm
      the expected photoisomerization in both homogeneous organic solution, and in
      vesicle bilayer membranes. Characteristic changes in the UV--visible spectra are
      consistent with fully reversible Z--E photoisomerization. Chromatographic
      separation of the Z and E isomers of a compound containing a single
      hemithioindigo chromophore confirmed the spectroscopic analysis and provided a
      quantitative analysis of the compositions of Z--E isomer mixtures.

PMID- 11325262
TI  - Molecular design and synthesis of artificial ion channels based on cyclic
      peptides containing unnatural amino acids.
AB  - A series of novel cyclic peptides composed of 3 to 5 dipeptide units with
      alternating natural-unnatural amino acid units, have been designed and
      synthesized, employing 5-(N-alkanoylamino)-3-aminobenzoic acid with a long
      alkanoyl chain as the unnatural amino acid. All cyclic peptides with
      systematically varying pore size, shape, and lipophilicity are found to form ion
      channels with a conductance of ca. 9 pS in aqueous KCl (500 mM) upon examination
      by the voltage clamp method. These peptide channels are cation selective with the
      permeability ratio P(Cl(-))/P(K(+)) of around 0.17. The ion channels formed by
      the neutral, cationic, and anionic cyclic peptides containing L-alanine, L
      lysine, and L-aspartate, respectively, show the monovalent cation selectivity
      with the permeability ratio P(Na(+))/P(K(+)) of ca. 0.39. On the basis of
      structural information provided by voltage-dependent blockade of the single
      channel current of all the tested peptides by Ca(2+), we inferred that each
      channel is formed from a dimer of the peptide with its peptide ring constructing
      the channel entrance and its alkanoyl chains lining across the membrane to build
      up the channel pore. The experimental results are consistent with an idea that
      the rate of ion conduction is determined by the nature of the hydrophobic
      alkanoyl chain region, which is common to all the channels.

PMID- 11325263
TI  - Generation of reactive low-valent titanium species using metal--arenes as
      efficient organic reductants for TiCl(3): applications to organic synthesis.
AB  - A comprehensive study on the use of metal-arene systems as organic reductants for
      TiCl(3) has resulted in an efficient method for the generation of highly reactive
      low-valent titanium (LVT) reagents. The activated titanium species could be
      prepared by refluxing a mixture of substoichiometric amounts of arenes, TiCl(3),
      and Li/Mg in THF or DME. Among the LVT reagents screened, TiCl(3)--Li-
      naphthalene--THF (reagent I) was the best for coupling of carbonyls to olefins.
      The reagent could carry out the McMurry olefination of both aromatic and
      aliphatic substrates at a lower temperature and in a much reduced time as
      compared to the conventional procedures. Subtle changes in the method of
      preparation of the LVT reagents influenced the stereoisomeric ratio of the
      olefins. The reagent was also useful for the synthesis of O- and N- heterocycles
      and vicinal diamines via intramolecular carbonyl coupling and reductive
      duplication of imines, respectively.

PMID- 11325264
TI  - The photochemistry of 2-(1-naphthyl)ethyl benzoates: cycloaddition and
      intramolecular exciplex formation.
AB  - The photochemistry of the 2-(1-naphthyl)ethyl benzoates 6 and 7 was examined in
      order to compare them to previously studied 2-arylethyl 4-cyanobenzoates that
      underwent a Norrish Type II fragmentation. The 1-naphthyl group was incorporated
      to provide a fluorescent chromophore for probing the intramolecular electron
      transfer proposed previously for the mechanism. The naphthalene fluorescence was
      quenched for both 6 and 7 although at very different rates. For 6, with the
      higher thermodynamic driving force (-68.9 kJ/mol), intramolecular electron
      transfer was fast in all solvents, independent of their polarity (cyclohexane to
      methanol). For 7, with the lower driving force (-26.5 kJ/mol) the process was
      fast only in polar solvents. Exciplex emission, observed for 6 (but not for 7),
      exhibited a large solvatochromic effect possibly indicating a high dipole moment
      (28 D) in polar solvents (stretched conformation) but a lower one (17 D) in
      nonpolar solvents (folded conformation). Finally, the 4-cyanobenzoate 6 was very
      unreactive photochemically. In contrast, benzoate 7 underwent a 2 + 2
      cycloaddition of the ester carbonyl to the naphthalene ring to give products 8
      and 9, a process for which we have found no precedent.

PMID- 11325265
TI  - Practical cobalt carbonyl catalysis in the thermal Pauson--Khand reaction:
      efficiency enhancement using Lewis bases.
AB  - In this report we have shown that the commercially available Co(2)(CO)(8) and
      Co(4)(CO)(12), and enyne--Co(2)(CO)(6) complexes, are sufficiently effective in
      catalyzing the Pauson--Khand reaction under one atmosphere of CO pressure. It was
      further demonstrated that the efficiencies of these cyclization protocols could
      be enhanced by the presence of cyclohexylamine. These procedures have also
      rendered more practical and highly convenient alternatives for the catalytic
      Pauson--Khand reaction. Most importantly, we have dispelled the common belief
      that Co(4)(CO)(12) is inactive in the Pauson--Khand reaction under one atmosphere
      of carbon monoxide. Of mechanistic importance is that these studies have also
      shown that the probable formation of Co(4)(CO)(12) is not necessarily a dead end
      pathway in the Co(2)(CO)(8)-catalyzed Pauson--Khand reaction. It is also of
      interest that substoichiometric amounts of Co(2)(CO)(8), in DME and in the
      presence of cyclohexylamine, are sufficient for the cyclocarbonylation of enynes
      under a nitrogen atmosphere. Our findings have provided more practical protocols
      for the Pauson-Khand reaction using catalytic amounts of cobalt carbonyl
      complexes and a better understanding of the influence of Lewis bases on their
      efficiency. These reports on the activity of Co(4)(CO)(12) are anticipated to
      develop into a convenient and practical alternative for Co(2)(CO)(8) catalysis.

PMID- 11325266
TI  - Quantitative calculations of antibody--antigen binding: steroid--DB3 binding
      energies by the linear interaction energy method.
AB  - Linear interaction energy/molecular dynamics calculations have been used to
      compute steroid/antibody binding energies. The absolute binding affinities of 10
      steroids to antibody DB3 and of a hapten to catalytic antibody 1E9 are computed
      and compared to experiment. A detailed analysis of the molecular origins of the
      observed binding patterns is provided. The binding energy of an untested steroid
      is predicted.

PMID- 11325267
TI  - Modular synthesis of pi-acceptor cyclophanes derived from 1,4,5,8
      naphthalenetetracarboxylic diimide and 1,5-dinitronaphthalene.
AB  - Three neutral cyclophanes were synthesized, and their association with indole, an
      aromatic pi-donor, was studied. The cyclophanes were designed to contain a rigid,
      hydrophobic binding cavity with 1,4,5,8-naphthalenetetracarboxylic diimide or 1,5
      dinitronaphthalene as the pi-acceptor. Two of the cyclophanes also contain a (S)
      (valine-leucine-alanine) tripeptide unit to provide chiral hydrogen bonding
      interactions with guest molecules. Despite the fact that these cyclophanes
      contain a hydrophobic binding cavity of appropriate dimensions, their association
      with indole is very weak. In the case of cyclophanes derived from 1,5
      dinitronaphthalene, steric interactions force the nitro groups out of the plane
      of the naphthalene ring, diminishing their effectiveness as pi-acceptors. A
      simple UV--visible titrimetric method, using N,N,N',N'-tetramethyl-1,4
      phenylenediamine (TMPD) as a pi-donor, was used to rank the pi-acceptor strength
      of these and other aromatic units. These titrations show that 1,4,5,8
      naphthalenetetracarboxylic diimide and 1,5-dinitronaphthalene derivatives are
      weaker pi-acceptors than viologens, which make good pi-acceptor cyclophanes.
      Methyl viologen is in turn a weaker pi-acceptor than anthaquinone disulfonate,
      suggesting that the latter may serve as a useful building block for pi-accepting
      cyclophane hosts.

PMID- 11325268
TI  - Design and synthesis of novel chiral dendritic species derived from bile acids.
AB  - Bile acids have been used for the first time as the building block for the
      construction of dendritic units. Orthogonally functionalized 7-deoxycholic and
      cholic acid derivatives were synthesized. The construction of a bile acid
      heptamer, a nonamer, and a decamer using the convergent strategy are described in
      detail. Chromatographic, spectral, and optical properties of these molecules have
      been investigated. Molecular modeling suggests that these molecules have globular
      shapes with nanometric dimensions.

PMID- 11325270
TI  - A stereospecific synthesis of oxazolinyloxiranes.
AB  - Lithiooxiranes 3a and 3b, generated by deprotonation of oxiranes 2a and 2b with s
      BuLi at -100 degrees C in Et(2)O, were found to be chemically very stable. trans
      Lithiooxirane 3a was also configurationally stable and reacted stereospecifically
      with electrophiles to give 4a--k. In contrast, cis-lithiooxirane 3b was found to
      be configurationally much less stable and reacted with electrophiles affording
      mixtures of diastereomers 4, 7, and 8. After only a very short reaction time, 3b
      too reacted with electrophiles highly stereospecifically. Deprotonation-
      deuteration and deprotonation--alkylation of chiral oxazolinyloxiranes 12a and
      12b to give oxiranes 12c and 12d were also examined. Semiempirical and ab initio
      calculations were carried out in an effort to explain the observed
      stereochemistry.

PMID- 11325269
TI  - Molecular basis for enantioselectivity of lipase from Chromobacterium viscosum
      toward the diesters of 2,3-dihydro-3-(4'-hydroxyphenyl)-1,1,3-trimethyl-1H-inden
      5-ol.
AB  - 2,3-Dihydro-3-(4'-hydroxyphenyl)-1,1,3-trimethyl-1H-inden-5-ol, 1, is a chiral
      bisphenol useful for preparation of polymers. Previous screening of commercial
      hydrolases identified lipase from Chromobacterium viscosum (CVL) as a highly
      regio- and enantioselective catalyst for hydrolysis of diesters of 1. The
      regioselectivity was > or =30:1 favoring the ester at the 5-position, while the
      enantioselectivity varied with acyl chain length, showing the highest
      enantioselectivity (E = 48 +/- 20 S) for the dibutanoate ester. In this paper, we
      use a combination of nonsymmetrical diesters and computer modeling to identify
      that the remote ester group controls the enantioselectivity. First, we prepared
      nonsymmetrical diesters of (+/-)-1 using another regioselective, but
      nonenantioselective, reaction. Lipase from Candida rugosa (CRL) showed the
      opposite regioselectivity (>30:1), allowing removal of the ester at the 4'
      position (the remote ester in the CVL-catalyzed reaction). Regioselective
      hydrolysis of (+/-)-1-dibutanoate (150 g) gave (+/-)-1-5-dibutanoate (89 g, 71%
      yield). Acylation gave nonsymmetrical diesters that varied at the 4'-position.
      With no ester at the 4'-position, CVL showed no enantioselectivity, while
      hindered esters (3,3-dimethylbutanoate) reacted 20 times more slowly, but
      retained enantioselectivity (E = 22). These results indicate that the remote
      ester group can control the enantioselectivity. Computer modeling confirmed these
      results and provided molecular details. A model of a phosphonate transition state
      analogue fit easily in the active site of the open conformation of CVL. A large
      hydrophobic pocket tilts to one side above the catalytic machinery. The tilt
      permits the remote ester at the 4'-position of only the (S)-enantiomer to bind in
      this pocket. The butanoate ester fits and fills this pocket and shows high
      enantioselectivity. Both smaller and larger ester groups show low
      enantioselectivity because small ester groups cannot fill this pocket, while
      longer ester groups extend beyond the pocket. An improved large-scale resolution
      of 1-dibutanoate with CVL gave (R)-(+)-1-dibutanoate (269 g, 47% yield, 92% ee)
      and (S)-(-)-1-4'-monobutanoate (245 g, 52% yield, 89% ee). Methanolysis yielded
      (R)-(+)-1 (169 g, 40% overall yield, >97% ee) and (S)-(-)-1 (122 g, 36% overall
      yield, >96% ee).

PMID- 11325271
TI  - Lithiated 4-isopropyl-3-(methylthiomethyl)-5,5-diphenyloxazolidin-2-one: a chiral
      formyl anion equivalent for enantioselective preparations of 1,2-diols, 2-amino
      alcohols, 2-hydroxy esters, and 4-hydroxy-2-alkenoates.
AB  - The heterocyclic compound specified in the title (and readily prepared from
      commercial precursors) has a sterically protected C==O group, so that direct
      lithiation by BuLi at the exocyclic CH(2) group is possible (3 --> Li-3). The
      lithiated N,S-acetal derivative (Li-3) adds diastereoselectively to aldehydes
      (Table 2), unsymmetrical ketones (Table 3), chalcone (1,4-addition, Scheme 2),
      and N-phosphinoyl- and N-sulfonylimines (Table 4). Protection of the newly formed
      OH groups (Scheme 3) and/or MeS/OH displacement by Hg(O(2)CCF(3))(2) in aqueous
      THF/acetonitrile converts the N,S-acetals into hemiaminals (--> 20) which, in
      turn, are readily cleaved to aldehydes, with recovery of the chiral auxiliary (1,
      Scheme 4). The aldehydes (especially those lacking alpha-carbonyl hydrogens) may
      be isolated, or they are trapped in situ by reduction to (selectively protected)
      diols or amino alcohols, by addition of Grignard or Li reagents, which provides
      diols with two stereogenic centers, by oxidation to give 2-hydroxy esters, or by
      olefination to provide 4-hydroxy-2-alkenoates (Scheme 5). The scope and
      limitations of the new, overall enantioselective transformation are determined,
      and the readily recovered chiral auxiliary used is compared with oxazolidinones
      of other substitution patterns (Scheme 7). The configuration of a number of
      products has been assigned by single-crystal X-ray diffraction (cf. Figure 5).
      These structures and similarities of NMR data led to configurational assignment
      of the other products (see formulas in the schemes and tables) by analogy. A
      simple mechanistic model for the stereochemical course of the addition of Li-3 to
      aldehydes and ketones is presented (Figure 6).

PMID- 11325273
TI  - Stereoselective and regioselective reaction of cyclic ortho esters with phenols.
AB  - Cyclic ortho esters undergo stereoselective and regioselective reaction with
      phenols when treated with BF(3) x OEt(2) at low temperatures. Attack of the
      phenol on the ortho ester occurs at an open carbon para to electron-donating
      groups on the phenol ("C-addition") or at the phenolic hydroxyl group ("O
      addition") depending on the nature of the cation formed from reaction of the
      ortho ester and BF(3) x OEt(2). Products resulting from O-addition undergo
      reversion to a mixture of starting phenol, C-addition product, and O-addition
      product if treated with BF(3) x OEt(2) at room temperature, but C-addition
      products are stable under the same conditions. X-ray structural analysis of the C
      addition compound indicates that its stereochemistry is opposite to that observed
      in reaction of similar ortho esters with chloride from TMSCl. However, the
      stereochemistry of the reaction can be rationalized by the ability of the ortho
      ester to isomerize via an intermediate benzylic cation and examination of the
      preferred trajectory of attack of the nucleophile on the intermediate oxonium
      ion.

PMID- 11325272
TI  - Synthesis of phosphorylated and sulfated glycosyl serines in the linkage region
      of the glycosaminoglycans.
AB  - We synthesized novel acidic glycans having acidic groups located in the linkage
      region of the glycosaminoglycans (GAGs). The targeted compounds, beta-D-Xyl(2P)
      Ser (1), beta-D-Gal(+/-6S)-(1-->4)-beta-D-Xyl(2P)-Ser (3 and 2), beta-D-Gal(+/
      6S)-(1-->3)-beta-D-Gal-(1-->4)-beta-D-Xyl(2P)-Ser (5 and 4), and beta-D-Gal-(1-
      >3)-beta-D-Gal(6S)-(1-->4)-beta-D-Xyl(2P)-Ser (6) contain phosphate and/or
      sulfate at the specified positions. Some of them (3, 5, and 6) are the first
      synthesized examples of natural-type glycoconjugates that simultaneously possess
      phosphate and sulfate as well as carboxylic acid.

PMID- 11325274
TI  - The secondary amine/nitric oxide complex ion R(2)N[N(O)NO](-) as nucleophile and
      leaving group in S9N)Ar reactions.
AB  - Ions of structure R(2)N[N(O)NO](-) and their alkylation products have seen
      increasing use as nitric oxide (NO)-generating agents for biomedical research
      applications. Here we show that such diazeniumdiolate anions can readily displace
      halide from a variety of electrophilic aza- or nitroaromatic substrates to form
      O(2)-arylated derivatives of structure R(2)N-N(O)=N-OAr. The site of arylation
      and the cis arrangement of the oxygens were confirmed by X-ray crystallography.
      Displacement by various nucleophiles showed R(2)N[N(O)NO](-) to be a reasonably
      good leaving group, with rate constants for displacement by hydroxide, methoxide,
      and isopropylamine that were between those of chloride and fluoride in the S(N)Ar
      reactions we surveyed. The Meisenheimer intermediate could be spectrally
      observed. These O(2)-aryl diazeniumdiolates proved capable of reacting with the
      nucleophilic sulfur of the HIV-1 p7 nucleocapsid protein's zinc finger assembly
      to eject the zinc, disrupting a structural motif critical to viral replication
      and suggesting possible utility in the drug discovery realm.

PMID- 11325275
TI  - Significant acceleration of 6 pi-azaelectrocyclization resulting from a
      remarkable substituent effect and formal synthesis of the ocular age pigment A2-E
      by a new method for substituted pyridine synthesis.
AB  - The remarkable acceleration of 6 pi-azaelectrocyclization due to the combination
      of the C4-carbonyl and the C6-alkenyl or phenyl substituents in 1-azatrienes was
      found. This observation was rationalized by considering the remarkable orbital
      interaction between the HOMO and LUMO of 1-azatrienes, which were obtained by
      molecular orbital calculations. The formal synthesis of the unusual retinal
      metabolite, A2-E, was achieved by two types of the new one-pot synthesis of
      substituted pyridines by utilizing the obtained facile 6 pi
      azaelectrocyclization, one of which is compatible with the proposed metabolic
      pathway of A2-E.

PMID- 11325276
TI  - Approaches to the synthesis of some tyrosine-derived marine sponge metabolites:
      synthesis of verongamine and purealidin N.
AB  - The oxidation of tyrosine ethyl ester (7) with Na(2)WO(4)/H(2)O(2) in ethanol,
      dimethyldioxirane in acetone, or methyltrioxorhenium/H(2)O(2) in EtOH gave the
      corresponding tyrosine oxime (8) in high yield. Controlled bromination of the
      aromatic ring gave the monobromo oxime (9), the dibromo oxime (10), or the
      spiroisoxazoline (11) depending upon reaction conditions. Synthesis of the known
      metabolite verongamine (15) was achieved by oxidation of O-methyl bromotyrosine
      methyl ester and amidation of the resulting oxime ester (14) with histamine. The
      mono- and di-bromotyrosine oxime derivatives (9 and 10) were further transformed
      into the naturally occurring nitriles (16 and 17) by base hydrolysis of the ester
      and acid-catalyzed decarboxylation. Wadsworth-Emmons olefination of the
      dibromobenzaldehyde (20b) with phosphonate (18) gave the pyruvate silylenolether
      (21b). Deprotection and in situ oxime formation gave the oxime ester (23b).
      Attempted purification of the pyruvate ester resulted in a homoaldol condensation
      yielding butenolide (22). Amidation of the oxime ester (23b) with histamine,
      followed by deprotection of the MOM ether gave the first synthesis of purealidin
      N (28). Oxidative spirocyclization of the phenolic oxime ester (23d) with a
      polymer-bound iodosyl diacetate gave the spiroisoxazoline (24) and represents a
      formal synthesis of aerothionin (26a), homoaerothionin (26b), and aerophobin-1
      (25).

PMID- 11325278
TI  - Concerted mechanisms of the reactions of methyl aryl carbonates with substituted
      phenoxide ions.
AB  - The reactions of 4-nitrophenyl, 2,4-dinitrophenyl, and 2,4,6-trinitrophenyl
      methyl carbonates (NPC, DNPC, and TNPC, respectively) with substituted phenoxide
      ions are subjected to a kinetic study in water at 25.0 degrees C, ionic strength
      0.2 M (KCl). Production of the leaving groups (the nitro derivatives) is followed
      spectrophotometrically. Under excess of the phenoxide ions pseudo-first-order
      rate coefficients (k(obsd)) are found throughout. Plots of k(obsd) vs substituted
      phenoxide concentration at constant pH are linear, with the slope (k(N))
      independent of pH. The Bronsted-type plots (log k(N) vs pK(a) of the phenols) are
      linear with slopes beta = 0.67, 0.48, and 0.52 for the phenolysis of NPC, DNPC,
      and TNPC, respectively. The magnitudes of these Bronsted slopes are consistent
      with a concerted mechanism. In the particular case of the phenolysis of NPC the
      expected hypothetical curvature center of the Bronsted plot for a stepwise
      mechanism should be pK(a)(0) = 7.1 (the pK(a) of 4-nitrophenol). This curvature
      does not appear within the pK(a) range of the substituted phenols studied (5.3-
      10.3), indicating that these reactions are concerted. The phenolysis of DNPC and
      TNPC should also be concerted in view of the even more unstable tetrahedral
      intermediates that would be formed if the reactions were stepwise. The reactions
      of the same substrates with pyridines are stepwise, which means that substitution
      of a pyridine moiety in a tetrahedral intermediate by a phenoxy group
      destabilizes the intermediate perhaps to the point of nonexistence. The k(N)
      values for the title reactions are larger than those for the concerted phenolysis
      of the corresponding ethyl S-aryl thiolcarbonates. The k(N) values found in the
      present reactions are subjected to a dual regression analysis as a function of
      the pK(a), of both the nucleophile and leaving group, the coefficients being
      beta(N) = 0.5 and beta(lg) = -0.3, respectively. These coefficients are
      consistent with a concerted mechanism.

PMID- 11325277
TI  - Application of furanyl carbamate cycloadditions toward the synthesis of
      hexahydroindolinone alkaloids.
AB  - A convenient synthesis of various substituted hexahydroindolinones has been
      achieved by an intramolecular Diels--Alder cycloaddition reaction (IMDAF) of
      furanyl carbamates bearing tethered alkenyl groups. The initially formed [4 + 2]
      cycloadduct undergoes nitrogen-assisted ring opening followed by deprotonation of
      the resulting zwitterion to give the rearranged ketone. The stereochemical
      outcome of the IMDAF cycloaddition has the sidearm of the tethered alkenyl group
      oriented syn with respect to the oxygen bridge. A synthetic route to (+/-)
      mesembrane and (+/-)-crinane was accomplished using this methodology. It was
      possible to carry out a stereoselective reduction of the initially formed
      hexahydroindolinone ring to produce the cis-3a-aryl-hydroindole skeleton. A
      related [4 + 2]-cycloaddition/rearrangement sequence was also used for a formal
      synthesis of the Chinese ornamental orchid (+/-)-dendrobine. The tricyclic
      alkaloid core was formed stereoselectivity from the thermolysis of N-[(2-methyl-2
      cyclopentenyl)methyl]-N-(4-isopropyl-furan-2-yl)carbamic acid tert-butyl ester.
      Kende's advanced intermediate 33 was prepared in seven additional steps by
      standard transformations, thereby completing a formal synthesis of (+/-)
      dendrobine.

PMID- 11325279
TI  - Enantioselective synthesis of the AB-ring system of the antitumor antibiotic
      tetrazomine.
AB  - The synthesis of the 1,2,3,4-tetrahydroisoquinoline moiety of tetrazomine was
      accomplished in 18 steps and in 3% overall yield from commercially available o
      anisaldehyde. The reaction sequence utilizes a Sharpless asymmetric
      dihydroxylation to install the stereocenter and an intramolecular Friedel--Crafts
      hydroxyalkylation with an N-protected 2-oxo-acetamide to close the heterocyclic
      ring.

PMID- 11325280
TI  - Use of a methoxy substituent in controlling the stereochemistry of intramolecular
      iron-mediated diene/olefin cyclocoupling.
AB  - A methodology for stereocontrol during the intramolecular coupling between
      cyclohexadiene--Fe(CO)(3) complexes and pendant alkenes is presented.
      Introduction of a methoxy group at the C(3) position of the diene moiety controls
      pre- and postcyclization rearrangements of the diene Fe(CO)(3) unit, allowing the
      preparation of spirolactams with defined relative stereochemistry and with a
      cyclohexenone framework, thus making this reaction a potentially valuable tool
      for the construction of quaternary carbon centers.

PMID- 11325281
TI  - Synthesis of new optically active propargylic fluorides and application to the
      enantioselective synthesis of monofluorinated analogues of fatty acid
      metabolites.
AB  - A new approach to obtain optically active unsaturated or polyunsaturated systems
      with a single fluorine atom in an allylic or propargylic position is reported.
      Central to this strategy is the high regio- and stereocontrol observed during the
      fluorination of propargylic alcohols allowing a short and efficient synthesis of
      1. Further, simple functional group transformations gave the enals 2 and 3. These
      three key intermediates were used for the preparation of optically active
      monofluorinated analogues of fatty acid metabolites.

PMID- 11325282
TI  - Porphyrins with exocyclic rings. 16. Synthesis and spectroscopic characterization
      of fluoranthoporphyrins, a new class of highly conjugated porphyrin chromophores.
AB  - Porphyrins with fused aromatic rings are under detailed investigation due to
      their unique spectroscopic properties. To gain more insights into the effects due
      to ring annealation on the porphyrin chromophore, a series of
      fluoranthoporphyrins have been synthesized. Reaction of 3-nitrofluoranthene with
      isocyanoacetate esters in the presence of a phosphazene base afforded good yields
      of the fluorantho[2,3-c]pyrrole esters 8. Cleavage of the ester moiety with KOH
      in ethylene glycol afforded the parent heterocycle 9, and this condensed with 2
      equiv of acetoxymethylpyrroles 10 in refluxing acetic acid-2-propanol to afford
      tripyrranes 11. Following cleavage of the tert-butyl ester protective groups with
      TFA, "3 + 1" condensation with pyrrole dialdehyde 12 gave the
      fluoranthoporphyrins 13 in good overall yields. In addition, reaction of
      tripyrrane 11 with acenaphthopyrrole dialdehyde 16 gave the mixed
      acenaphthofluoranthoporphyrin 17 in excellent yields. A difluoranthoporphyrin 18
      was also prepared via a "2 + 2" MacDonald condensation. Reaction of
      fluoranthopyrrole 8a with dimethoxymethane in the presence of p-toluenesulfonic
      acid gave the symmetrical dipyrrylmethane 19, and following ester saponification,
      this was condensed with a dipyrrylmethane dialdehyde to afford the adj
      difluoranthoporphyrin 18. The UV--vis spectra for these fluoranthoporphyrins gave
      a series of three broadened absorptions in the Soret band region, although the Q
      bands were little effected by ring fusion. The nickel(II), copper(II), and zinc
      chelates were more unusual, showing strong absorptions near 600 nm.
      Difluoranthoporphyrin 18 showed many of the same spectroscopic features, although
      the presence of two ring fusions gave rise to an increase in the spectroscopic
      shifts. The mixed system 17 gave spectra that showed larger red shifts due to the
      acenaphthylene unit combined with the features due to the fluoranthene rings.
      This work further demonstrates the utility of aromatic ring fusion in altering
      the properties of porphyrinoid systems.

PMID- 11325283
TI  - Poly(ethylene glycol)-supported bisoxazolines as ligands for catalytic
      enantioselective synthesis.
AB  - Two chiral bisoxazolines (box) supported on a modified poly(ethylene glycol)
      (PEG) have been prepared by a reaction sequence that involved formation of the
      properly functionalized box and their attachment to the polymer matrix by means
      of a spacer and a linker. The solubility properties of PEG allowed use of the
      supported box as ligands in some catalytic asymmetric transformations carried out
      under homogeneous conditions and to recover the ligands as if bound to an
      insoluble support. When the supported box were employed in combination with
      Cu(II) salts in the Diels-Alder cycloaddition between cyclopentadiene and N
      acryloyloxazolidinone, low levels of enantioselectivity were observed (up to 45%
      ee). Much better results were obtained in the cyclopropanation of styrenes
      carried out in the presence of CuOTf (up to 93% ee) and in the ene-reaction
      between alpha-methylstyrene or methylenecyclohexane and ethylglyoxalate (up to
      95% ee). One of the ligands, readily recovered by precipitation and filtration,
      was recycled two times in the ene-reaction with marginal loss in the catalytic
      activity and very limited erosion of the enantioselectivity.

PMID- 11325284
TI  - Synthesis of polycyclic guanidines by cyclocondensation reactions of N
      amidinyliminium ions.
AB  - A new method for the synthesis of polycyclic guanidines is described. The N
      amidinyliminium ion generated from alpha-(phenylthio)amidine precursor 16 by
      reaction with Cu(OTf)(2) undergoes cyclocondensation with 1,3-dienes, styrenes,
      and beta-dicarbonyl compounds to give 1-iminohexahydropyrrolo[1,2-c]pyrimidines
      having side chains at C3 and C7. In all cases, major products have a cis
      relationship of the C7 side chain and angular C4a hydrogen, whereas C3 side
      chains are incorporated with lower stereoselectivity (dr = 2--5:1) in
      cyclocondensations with dienes and styrenes to give stereoisomer 39 as the major
      product. In contrast to most cycloadditions of alkenes with N-acyliminium ions,
      cyclocondensations of alkenes with N-amidinyliminium ions proceed by a stepwise
      pathway. Cyclocondensation of the cognate ureido aminal 31 with styrene provides
      the rare 2-imino-5,6-dihydro-4H-1,3-oxazine derivative 32, rather than a
      pyrimidine as the major product. The high stereoselectivity observed in
      condensations of 16 with benzyl acetoacetate to afford Biginelli adduct 29
      supports the intermediacy of N-amidinyliminium ions in related tethered Biginelli
      condensations of guanidines reported earlier from our laboratories.

PMID- 11325285
TI  - Intramolecular [4 + 2] cycloaddition reaction of six- and seven-membered cyclic N
      allyl-C-arylethynyl iminium salts.
AB  - N-Allyl-2-(het)arylethynyl-3,4,5,6-tetrahydropyridinium triflates 1c,d,e and N
      allyl-2-(het)aryl-4,5,6,7-tetrahydro-3H-azepinium triflates 1g,h undergo a
      thermal isomerization reaction leading to derivatives of [a,f]-annulated
      isoindolium salts 2 in good yields. Similarly, N-allyl-2-phenylethynyl-pyridinium
      triflate 4 is transformed into the condensed pyridinium salt 5. An intramolecular
      [4 + 2] cycloaddition reaction, in which the (het)arylethynyl moiety acts as the
      4pi component, is considered as the key step of this transformation. In contrast,
      the related N-allyl-4,5-dihydro-3H-pyrrolium salts 1a,b and N-homoallyl-3,4,5,6
      tetrahydropyridinium salt 1f undergo unspecific decomposition under thermal
      impact.

PMID- 11325286
TI  - Biradical intermediates in the photoisomerization of
      dibenzodihydropentalenofurans to dibenzosemibullvalenes.
AB  - The photoisomerization of a few substituted dibenzodihydropentalenofurans to the
      corresponding dibenzosemibullvalenes is reported. Steady-state photolysis of the
      dibenzodihydropentalenofurans 3a--d gave the corresponding dibenzosemibullvalenes
      2a--d in nearly quantitative yields. The quantum yields of this
      photoisomerization were found to be in the range 0.17--0.26. Laser flash
      photolysis studies of the dibenzodihydropentalenofurans 3a-e showed transients,
      with absorption maxima around 410 nm and decaying by first-order kinetics. The
      lifetimes were in the range 14--30 micros in degassed benzene at 25 degrees C.
      These transients were readily quenched (trapped) by molecular oxygen, and the
      Stern-Volmer quenching constants were found to be in the range (2.45--3.17) x
      10(9) M(-1) s(-1). As a representative example, the 1,3-biradical intermediate
      from 3e was trapped by molecular oxygen to give the corresponding endoperoxide
      11e. The transients were weakly quenched by triplet/radical quenchers such as
      2,2,6,6-tetramethylpiperinyl-1-oxy (TEMPO) and 4-hydroxy-2,2,6,6
      tetramethylpiperinyl-1-oxy (HTEMPO), and the quenching constants are found to be
      in the range (1.09--3.19) x 10(6) M(-1) s(-1). The decay rates of the transients
      were found to be temperature dependent and obeyed the Arrhenius equation. For
      example, the activation energy of the transient from 3a was approximately 4.5
      kcal mol(-1) and the Arrhenius preexponential factor log(A/s(-1)) for the decay
      of the transients was approximately 7.5. On the basis of our studies, these
      transients were assigned as the ground-state triplet biradicals, generated by the
      cleavage of the C--O bond of the starting dibenzodihydropentalenofurans.

PMID- 11325287
TI  - Steps to demarcate the effects of chromophore aggregation and planarization in
      poly(phenyleneethynylene)s. 2. The photophysics of 1,4-diethynyl-2-fluorobenzene
      in solution and in crystals.
AB  - Crystals of 1,4-bis(2-hydroxy-2-methyl-3-butynyl)-2-fluorobenzene 4 have a rich
      packing structure with four distinct molecules in the unit cell. A complex
      hydrogen bonding network results in the formation of cofacial trimers, cofacial
      dimers, and monomers within the same unit cell. Given a remarkable opportunity to
      investigate the effect of aggregation on the photophysics of 1,4
      diethynylbenzenes, we analyzed the absorption, diffuse reflectance, and emission
      spectra of compound 4 in solutions and in crystals. Diffuse reflectance and
      fluorescence excitation revealed a red-shifted absorption that is absent in
      dilute solution but becomes observable at high concentrations and low
      temperatures. The fluorescence emission in the solid state is dual with
      components assigned to monomers and aggregates. The excitation and emission
      assigned to the monomer are nearly identical in crystals and dilute solutions.
      The absorption and emission bands assigned to aggregates are broad and red
      shifted by 60--80 nm. As expected for a sample with absorbers and emitters with
      different energies and incomplete equilibration, efficient monomer-to-aggregate
      energy transfer was observed by a proper selection of excitation wavelengths. The
      fluorescence quantum yield of 4 in solution is relatively low (Phi(F) = 0.15) and
      the singlet lifetime short (tau(F) = 3.8 ns). A lower limit for the triplet yield
      of Phi(T) = 0.64 was determined indirectly in solution by (1)O(2) sensitization,
      and a relatively strong and long-lived phosphorescence was observed in low
      temperature glasses and in crystals at 77 K.

PMID- 11325288
TI  - Determination of the nucleophilicities of N,N-bis(silyloxy)enamines.

PMID- 11325289
TI  - Stereoselective access to hydroxy oxetanes and tetrahydrooxepines through
      isomerization of oxiranyl ethers.

PMID- 11325291
TI  - A theoretical study of the molecular mechanism of the reaction between N,N
      dimethylmethyleneammonium cation and cyclopentadiene.

PMID- 11325290
TI  - New access to C-branched sugars and C-disaccharides under indium promoted Barbier
      type allylations in aqueous media.

PMID- 11325292
TI  - Linear versus Y-topology in conjugated polyene dications: questioning Y
      aromaticity.

PMID- 11325293
TI  - Electrophilic azidation for stereoselective synthesis of 2-azido-2-deoxyaldono
      1,5-lactones.

PMID- 11325294
TI  - Asymmetric synthesis of a new 8-hydroxyquinoline-derived alpha-amino acid and its
      incorporation in a peptidylsensor for divalent zinc.

PMID- 11325296
TI  - Oxidation of organic sulfides by Br(2) and H(2)O(2). Electrophilic and free
      radical processes.

PMID- 11325295
TI  - Diphenylacetylene and the LICKOR superbase: o,o'-dimetalation and reaction with
      electrophiles. A convenient synthesis of o,o'-disubstituted diphenylacetylenes.

PMID- 11325297
TI  - Oxidation of benzyl chlorides and bromides to benzoic acids with 30 hydrogen
      peroxide in the presence of Na(2)WO(4), Na(2)VO(4), or Na(2)MoO(4) under organic
      solvent-free conditions.

PMID- 11325298
TI  - Highly regio- and enantioselective palladium-catalyzed allylic amination with
      sodium diformylamide.

PMID- 11325299
TI  - Synthesis of the C(1')--C(11') segment of leucascandrolide A.

PMID- 11325300
TI  - Deoxyamphimedine, a new pyridoacridine alkaloid from two tropical Xestospongia
      sponges.

PMID- 11325303
TI  - Cell biology update: a decade of simulating space on earth.

PMID- 11325304
TI  - New therapy promising for genital herpes.

PMID- 11325305
TI  - Mixed message on prescription drug abuse.

PMID- 11325309
TI  - From the Food and Drug Administration.

PMID- 11325312
TI  - Outcomes of a trial of HIV-1 immunogen in patients with HIV infection.

PMID- 11325313
TI  - Outcomes of a trial of HIV-1 immunogen in patients with HIV infection.

PMID- 11325314
TI  - Outcomes of a trial of HIV-1 immunogen in patients with HIV infection.

PMID- 11325315
TI  - Outcomes of a trial of HIV-1 immunogen in patients with HIV infection.

PMID- 11325316
TI  - Outcomes of a trial of HIV-1 immunogen in patients with HIV infection.

PMID- 11325318
TI  - Endocarditis due to Streptococcus mitis with high-level resistance to penicillin
      and ceftriaxone.

PMID- 11325319
TI  - Chemical andropause and amyloid-beta peptide.

PMID- 11325320
TI  - Grip strength and subjective fatigue in patients with primary biliary cirrhosis.

PMID- 11325321
TI  - Cardiorespiratory events recorded on home monitors: Comparison of healthy infants
      with those at increased risk for SIDS.
AB  - CONTEXT: Home monitors designed to identify cardiorespiratory events are
      frequently used in infants at increased risk for sudden infant death syndrome
      (SIDS), but the efficacy of such devices for this use is unproven. OBJECTIVE: To
      test the hypothesis that preterm infants, siblings of infants who died of SIDS,
      and infants who have experienced an idiopathic, apparent life-threatening event
      have a greater risk of cardiorespiratory events than healthy term infants.
      DESIGN: Longitudinal cohort study conducted from May 1994 through February 1998.
      SETTING: Five metropolitan medical centers in the United States. PARTICIPANTS: A
      total of 1079 infants (classified as healthy term infants and 6 groups of those
      at risk for SIDS) who, during the first 6 months after birth, were observed with
      home cardiorespiratory monitors using respiratory inductance plethysmography to
      detect apnea and obstructed breathing. MAIN OUTCOME MEASURES: Occurrence of
      cardiorespiratory events that exceeded predefined conventional and extreme
      thresholds as recorded by the monitors. RESULTS: During 718 358 hours of home
      monitoring, 6993 events exceeding conventional alarm thresholds occurred in 445
      infants (41%). Of these, 653 were extreme events in 116 infants (10%), and of
      those events with apnea, 70% included at least 3 obstructed breaths. The
      frequency of at least 1 extreme event was similar in term infants in all groups,
      but preterm infants were at increased risk of extreme events until 43 weeks'
      postconceptional age. CONCLUSIONS: In this study, conventional events are quite
      common, even in healthy term infants. Extreme events were common only in preterm
      infants, and their timing suggests that they are not likely to be immediate
      precursors to SIDS. The high frequency of obstructed breathing in study
      participants would likely preclude detection of many events by conventional
      techniques. These data should be important for designing future monitors and
      determining if an infant is likely to be at risk for a cardiorespiratory event.

PMID- 11325322
TI  - Management of chronic tension-type headache with tricyclic antidepressant
      medication, stress management therapy, and their combination: a randomized
      controlled trial.
AB  - CONTEXT: Chronic tension-type headaches are characterized by near-daily headaches
      and often are difficult to manage in primary practice. Behavioral and
      pharmacological therapies each appear modestly effective, but data are lacking on
      their separate and combined effects. OBJECTIVE: To evaluate the clinical efficacy
      of behavioral and pharmacological therapies, singly and combined, for chronic
      tension-type headaches. DESIGN AND SETTING: Randomized placebo-controlled trial
      conducted from August 1995 to January 1998 at 2 outpatient sites in Ohio.
      PARTICIPANTS: Two hundred three adults (mean age, 37 years; 76% women) with
      diagnosis of chronic tension-type headaches (mean, 26 headache d/mo).
      INTERVENTIONS: Participants were randomly assigned to receive tricyclic
      antidepressant (amitriptyline hydrochloride, up to 100 mg/d, or nortriptyline
      hydrochloride, up to 75 mg/d) medication (n = 53), placebo (n = 48), stress
      management (eg, relaxation, cognitive coping) therapy (3 sessions and 2 telephone
      contacts) plus placebo (n = 49), or stress management therapy plus antidepressant
      medication (n = 53). MAIN OUTCOME MEASURES: Monthly headache index scores
      calculated as the mean of pain ratings (0-10 scale) recorded by participants in a
      daily diary 4 times per day; number of days per month with at least moderate pain
      (pain rating >/=5), analgesic medication use, and Headache Disability Inventory
      scores, compared by intervention group. RESULTS: Tricyclic antidepressant
      medication and stress management therapy each produced larger reductions in
      headache activity, analgesic medication use, and headache-related disability than
      placebo, but antidepressant medication yielded more rapid improvements in
      headache activity. Combined therapy was more likely to produce clinically
      significant (>/=50%) reductions in headache index scores (64% of participants)
      than antidepressant medication (38% of participants; P =.006), stress management
      therapy (35%; P =.003), or placebo (29%; P =.001). On other measures the combined
      therapy and its 2 component therapies produced similar outcomes. CONCLUSIONS: Our
      results indicate that antidepressant medication and stress management therapy are
      each modestly effective in treating chronic tension-type headaches. Combined
      therapy may improve outcome relative to monotherapy.

PMID- 11325323
TI  - Prevalence of C282Y and H63D mutations in the hemochromatosis (HFE) gene in the
      United States.
AB  - CONTEXT: Population-based estimates of the prevalence of disease-associated
      mutations, such as hemochromatosis (HFE) gene mutations, are needed to determine
      the usefulness of genetic screening. OBJECTIVE: To estimate the prevalence of the
      HFE mutations C282Y and H63D in the US population. DESIGN: Cross-sectional
      population-based study of samples in the DNA bank from phase 2 of the Third
      National Health and Nutrition Examination Survey conducted from 1992 to 1994.
      SETTING AND PARTICIPANTS: Genotyped samples of cells from a total of 5171
      participants, cross-classified by sex, age, and race/ethnicity in the analysis.
      MAIN OUTCOME MEASURES: Estimates of the prevalence of C282Y and H63D mutations.
      RESULTS: The prevalence of C282Y homozygosity is estimated to be 0.26% (95%
      confidence interval [CI], 0.12%-0.49%); 1.89% (95% CI, 1.48%-2.43%) for H63D
      homozygosity; and 1.97% (95% CI, 1.54%-2.49%) for compound heterozygosity. The
      prevalence estimates for C282Y heterozygosity (C282Y/wild type) are 9.54% among
      non-Hispanic whites, 2.33% among non-Hispanic blacks, and 2.75% among Mexican
      Americans. The prevalence estimates of the C282Y mutation in the US population
      are 5.4% (95% CI, 4.7%-6.2%) and 13.5% (95% CI, 12.5%-14.8%) for the H63D
      mutation. CONCLUSIONS: Estimates of prevalence of HFE mutations are within the
      expected range for non-Hispanic whites and blacks but the estimated prevalence of
      the C282Y mutation among Mexican-Americans is less than expected. Mutation data
      now need to be linked to clinically relevant indices, such as transferrin
      saturation level.

PMID- 11325324
TI  - Self-referral in point-of-service health plans.
AB  - CONTEXT: Most health maintenance organizations offer products with loosened
      restrictions on patients' access to specialty care. One such product is the point
      of-service (POS) plan, which combines "gatekeeping" arrangements with the ability
      to self-refer at increased out-of-pocket costs. Few data are available from
      formal evaluations of this new type of plan. OBJECTIVES: To comprehensively
      describe the self-referral process in POS plans by quantifying rates of self
      referral, identifying patients most likely to self-refer, characterizing
      patients' reasons for self-referral, and assessing satisfaction with specialty
      care. DESIGN: Retrospective cohort analysis using administrative databases
      composed of members aged 0 to 64 years who were enrolled in 3 POS health plans in
      the Midwest (n = 265 843), Northeast (n = 80 292), and mid-Atlantic (n = 39 888)
      regions for 6 to 12 months in 1996, and a 1997 telephone survey of specialty care
      users (n = 606) in the midwestern plan. MAIN OUTCOME MEASURES: Self-referred
      service use and charges, reasons for self-referral, and satisfaction with
      specialty care. RESULTS: Overall, 8.8% of enrollees in the midwestern POS plan,
      16.7% in the northeastern plan, and 17.3% in the mid-Atlantic plan self-referred
      for at least 1 physician or nonphysician clinician visit. The proportions of
      enrollees self-referring to generalists (4.7%-8.5%) were slightly higher than the
      proportions self-referring to specialists (3.7%-7.2%) across all 3 plans. Nine
      percent to 16% of total charges were due to self-referral. The chances of self
      referral to a specialist were increased for patients with chronic and orthopedic
      conditions, higher cost sharing for physician-approved services, and less
      continuity with their regular physician. Patients who self-referred to
      specialists preferred to access specialty care directly (38%), reported
      relationship problems with their regular physicians (28%), had an ongoing
      relationship with a specialist (23%), were confused about insurance rules (8%),
      and did not have a regular physician (3%). Compared with those referred to
      specialists by a physician, patients who self-referred were more satisfied with
      the specialty care they received. CONCLUSIONS: Having the option to self-refer is
      enough for most POS plan enrollees; 93% to 96% of enrollees did not exercise
      their POS option to obtain specialty care via self-referral during a 1-year
      interval. The potential downside of uncoordinated, self-referred service use in
      POS health plans is limited and counterbalanced by higher patient satisfaction
      with specialist services.

PMID- 11325325
TI  - Clinical breast and pelvic examination requirements for hormonal contraception:
      Current practice vs evidence.
AB  - Clinical breast and pelvic examinations are commonly accepted practices prior to
      provision of hormonal contraception. Such examinations, however, may reduce
      access to highly effective contraceptive methods, and may therefore increase
      women's overall health risks. These unnecessary requirements also involve ethical
      considerations and unwittingly reinforce the widely held but incorrect perception
      that hormonal contraceptive methods are dangerous. This article reviews and
      summarizes the relevant medical literature and policy statements from major
      organizations active in the field of contraception. Consensus developed during
      the last decade supports a change in practice: hormonal contraception can safely
      be provided based on careful review of medical history and blood pressure
      measurement. For most women, no further evaluation is necessary. Pelvic and
      breast examinations and screening for cervical neoplasia and sexually transmitted
      infection, while important in their own right, do not provide information
      necessary for identifying women who should avoid hormonal contraceptives or who
      need further evaluation before making a decision about their use.

PMID- 11325326
TI  - The multifaceted challenges of Proteus syndrome.
AB  - Proteus syndrome is a rare and sporadic disorder that causes postnatal overgrowth
      of multiple tissues in a mosaic pattern. The overgrowth can involve skin,
      subcutaneous tissue, connective tissue (including bone), the central nervous
      system, and viscera. Complications of Proteus syndrome include, among others,
      progressive skeletal deformities, invasive lipomas, benign and malignant tumors,
      and deep venous thrombosis with pulmonary embolism. Care of patients with Proteus
      syndrome presents significant challenges to both physicians and parents because
      of the various medical as well as psychosocial consequences of the disease.
      Herein, the case of a 5-year-old patient who manifested a number of these
      complications is presented. Current knowledge about the diagnosis, natural
      history, etiology, and management of the disorder is reviewed.

PMID- 11325327
TI  - What do home monitors contribute to the SIDS problem?

PMID- 11325330
TI  - msJAMA: The evolution of the physician's role.

PMID- 11325331
TI  - msJAMA: Medical career choices: traditional and new possibilities.

PMID- 11325332
TI  - msJAMA: Legal medicine: a professional option.

PMID- 11325333
TI  - msJAMA: The war for talent: physicians in management consulting.

PMID- 11325334
TI  - msJAMA: Why be a medical editor?

PMID- 11325340
TI  - Atypical Herpes simplex keratitis (HSK) presenting as a perforated corneal ulcer
      with a large infiltrate in a contact lens wearer: multinucleated giant cells in
      the Giemsa smear offered a clue to the diagnosis.
AB  - PURPOSE: To report a case of atypical herpes simplex keratitis initially
      diagnosed as bacterial keratitis, in a contact lens wearer. RESULTS: Case report
      of an 18-year-old woman using contact lenses who presented with pain, redness and
      gradual decrease in vision in the right eye. Examination revealed a paracentral
      large stromal infiltrate with a central 2-mm perforation. Corneal and
      conjunctival scrapings were collected for microbiological investigations. Corneal
      tissue was obtained following penetrating keratoplasty. Corneal scraping revealed
      no microorganisms. Giemsa stained smear showed multinucleated giant cells.
      Conjunctival, corneal scrapings and tissue were positive for herpes simplex virus
      - 1 (HSV) antigen. Corneal tissue was positive for HSV DNA by PCR. CONCLUSIONS:
      Atypical HSV keratitis can occur in contact lens wearers. A simple investigation
      like Giemsa stain may offer a clue to the diagnosis.

PMID- 11325341
TI  - Co-localization of GLUT1 and GLUT4 in the blood-brain barrier of the rat
      ventromedial hypothalamus.
AB  - The ventromedial hypothalamus (VMH) has been proposed to be a glucose sensor
      within the brain and appears to play a critical role in initiating the
      counterregulatory response to hypoglycemia. Transport of glucose across the brain
      capillaries and into neurons in this region is mediated by different isoforms of
      the sodium-independent glucose transporter gene family. The objective of the
      present study was to identify the specific glucose transporter isoforms present,
      as well as their cellular localization, within the VMH. Immunohistochemistry was
      performed for GLUT1, GLUT2 and GLUT4 in frozen sections of hypothalami from
      normal rats. GLUT1 was present on the endothelial cells of the blood-brain
      barrier (BBB) of the VMH. GLUT2 immunoreactivity was seen in the ependymal cells
      of the third ventricle and in scattered cells in the arcuate and periventricular
      nuclei. There was no GLUT2 expression in the VMH. The insulin-sensitive GLUT4
      isoform was localized to vascular structures within the VMH. Double-labeled
      immunohistochemistry demonstrated co-localization of GLUT4 with GLUT1 and with
      the tight junction protein ZO-1 in the VMH and suggested that VMH GLUT4
      expression was restricted to the BBB. The role of GLUT4 in the brain and within
      the VMH is unknown, but given its location on the BBB, it may participate in
      brain sensing of blood glucose concentrations.

PMID- 11325342
TI  - Functional alterations in gap junction channels formed by mutant forms of
      connexin 32: evidence for loss of function as a pathogenic mechanism in the X
      linked form of Charcot-Marie-Tooth disease.
AB  - CMTX, the X-linked form of Charcot-Marie-Tooth disease, is an inherited
      peripheral neuropathy arising in patients with mutations in the gene encoding the
      gap junction protein connexin 32 (Cx32). In this communication, we describe the
      expression levels and biophysical parameters of seven mutant forms of Cx32
      associated with CMTX, when expressed in paired Xenopus oocytes. Paired oocytes
      expressing the R15Q and H94Q mutants show junctional conductances not
      statistically different from that determined for Cx32WT, though both show a trend
      toward reduced levels. The S85C and G12S mutants induce reduced levels of
      junctional conductance. Three other mutants (R15W, H94Y and V139M) induce no
      conductance above baseline when expressed in paired oocytes. Analysis of the
      conductance voltage relations for these mutants shows that the reduced levels of
      conductance are entirely (H94Y and V139M) or partly (S85C and R15W) explicable by
      a reduced open probability of the mutant hemichannels. The R15Q and H94Q
      mutations also show alterations in the conductance voltage relations that would
      be expected to minimally (H94Q) or moderately (R15Q) reduce the available gap
      junction communication pathway. The reduction in G12S induced conductance cannot
      be explained by alterations in hemichannel open probability and are more likely
      due to reduced junction formation. These results demonstrate that many CMTX
      mutations lead to loss of function of Cx32. For these mutations, the loss of
      function model is likely to explain the pathogenesis of CMTX.

PMID- 11325343
TI  - Characterization of cyclin D1 expression in a rat global model of cerebral
      ischemia.
AB  - During normal development of the central nervous system there is expression of
      cyclins that regulate the progression of cells through various stages of mitosis.
      Cyclins have also been implicated in neuronal degeneration and apoptosis in adult
      brain, especially cyclin D1 as it is permissive for the transition from growth
      phase to synthesis phase in mitotic cell division. There is controversy as to
      whether cyclin D1 expression increases in both in vitro and in vivo models of
      cerebral ischemia. In this study we use immunohistochemistry and Western blot
      analysis to characterize cyclin D1 expression in an in vivo rat global model of
      cerebral ischemia to address the hypothesis that cyclin D1 alterations are
      involved in ischemic neuronal death. Although there was no change in cyclin D1
      expression in either the vulnerable CA1 or resistant CA3 regions of the
      hippocampus prior to neuronal cell death (<3 days reperfusion), concomitant with
      the death of CA1 neurons and the loss of cyclin D1 in these cells, there was an
      increase in non-neuronal cyclin D1 positive cells. Some of the non-neuronal
      cyclin D1 expressing cells were identified to be activated microglia. In contrast
      to the cytoplasmic expression of cyclin D1 in neurons, the cyclin D1 expression
      in the microglia and other non-neuronal cells in CA1 was both nuclear and
      cytosolic. This study suggests that cyclin D1 does not play a role in the death
      of vulnerable CA1 neurons in global ischemia.

PMID- 11325344
TI  - Low-threshold N-methyl-D-aspartate receptor function correlates negatively with
      learning.
AB  - The intermediate, medial hyperstriatum ventrale (IMHV) is an area of the
      forebrain of the domestic chick which exhibits great plasticity. Moreover, there
      is a strong link between plasticity in the IMHV and specific changes in
      behaviour. The IMHV in vitro is still plastic, and many of its physiological
      properties are age-dependent, peaking in slices taken from 3- or 4-day-old birds.
      This 'window' coincides with an important transitional period in a chick's normal
      behavioural development. It has also been claimed that reversal training is at
      its most effective in 3- and 4-day-old birds - a proposition which was confirmed
      by the experiments reported here. A combination of in vivo training followed by
      in vitro electrophysiology also revealed that the function of low-threshold N
      methyl-D-aspartate receptors (one of the age-related variables) is negatively
      related to the effectiveness of reversal training, when age is held constant.

PMID- 11325345
TI  - Apolipoprotein E deposition and astrogliosis are associated with maturation of
      beta-amyloid plaques in betaAPPswe transgenic mouse: Implications for the
      pathogenesis of Alzheimer's disease.
AB  - A transgenic mouse expressing the human beta-amyloid precursor protein with the
      'Swedish' mutation, Tg2576, was used to investigate the mechanism of beta-amyloid
      (Abeta) deposition. Previously, we have reported that the major species of Abeta
      in the amyloid plaques of Tg2576 mice are Abeta1-40 and Abeta1-42. Moreover,
      Abeta1-42 deposition precedes Abeta1-40 deposition, while Abeta1-40 accumulates
      in the central part of the plaques later in the pathogenic process. Those data
      indicate that Abeta deposits in Tg2576 mice have similar characteristics to those
      in Alzheimer's disease. In the present study, to understand more fully the
      amyloid deposition mechanism implicating Alzheimer's disease pathogenesis, we
      examined immunohistochemically the distributions of apolipoprotein E (apoE) and
      Abeta in amyloid plaques of aged Tg2576 mouse brains. Our findings suggest that
      Abeta1-42 deposition precedes apoE deposition, and that Abeta1-40 deposition
      follows apoE deposition during plaque maturation. We next examined the
      relationship between apoE and astrogliosis associated with amyloid plaques using
      a double-immunofluorescence method. Extracellular apoE deposits were always
      associated with reactive astrocytes whose processes showed enhancement of apoE
      immunoreactivity. Taken together, the characteristics of amyloid plaques in
      Tg2576 mice are similar to those in Alzheimer's disease with respect to apoE and
      astrogliosis. Furthermore, apoE deposition and astrogliosis may be necessary for
      amyloid plaque maturation.

PMID- 11325346
TI  - Bending the lamprey spinal cord causes a slowly-decaying increase in the
      frequency of fictive swimming.
AB  - It is well known that rhythmic lateral bending of the isolated lamprey spinal
      cord/notochord can entrain the central pattern generator (CPG) for locomotion.
      During entrainment, the CPG's frequency is equal to the bending frequency. We
      report here that bending can also have a slowly-decaying excitatory effect on the
      CPG's frequency. Experiments were performed in which the caudal end of a 30-50
      segment piece of spinal cord/notochord was repeatedly rhythmically bent for 0.5
      12 cycles. A slowly-decaying excitation was said to be present if after the
      termination of bending the CPG's frequency was significantly greater than
      baseline and decayed back to baseline with a time constant of one or more cycles.
      In 14 of 16 animals, a slowly-decaying excitation could be evoked by bending. In
      five of the nine animals tested, this slowly-decaying excitation could be evoked
      with bending frequencies both faster and slower than the baseline frequency.
      Depending on the animal, the slowly-decaying excitation could be elicited by as
      little as one-half cycle of bending and by bending amplitudes as small as 6-21
      degrees peak deflection. We interpret these data as evidence of a second effect
      of bending distinct from the phase-dependent effect that produces entrainment.

PMID- 11325347
TI  - Kainic acid-induced dorsal and ventral hippocampal seizures in rats.
AB  - Despite reports of differing regional seizure susceptibility in the hippocampus,
      hippocampal initiation of limbic seizures has not been precisely localized. We
      compared seizures induced by kainic acid microinjection into the left dorsal and
      ventral hippocampus of rats. Discharges following ventral injections rapidly
      propagated to the left amygdala and sensorimotor cortex unlike seizures following
      dorsal injections. The ventral group showed various ictal behaviors including
      motor manifestations, while dorsally injected rats showed only immobilization.

PMID- 11325349
TI  - Retrograde tracing of zinc-enriched (ZEN) neuronal somata in rat spinal cord.
AB  - The zinc selenide autometallographic (ZnSeAMG) technique for tracing the
      retrograde axonal transport of zinc ions in zinc-enriched (ZEN) neurons was used
      to map the distribution of ZEN neuronal somata in rat spinal cord. After a local
      injection of sodium selenide into the dorsal or ventral horn, ZnSeAMG-labeled ZEN
      neurons appeared in Rexed's laminae V, VII and X while laminae I and II were
      void. A few scattered ZEN somata were observed in the remaining laminae. The
      labeled neurons differed in shape and size, and the relatively high level of
      labeled somata around the injection site suggests that many ZEN neurons have
      relatively short axons or boutons en passage close to the neuronal origin.
      Ultrastructurally, the retrogradely transported zinc selenide clusters were found
      in the lysosomes of ZEN somata and proximal dendrites. Electron microscopic
      studies also revealed two different kinds of ZEN terminals: (1) terminals with
      flat synaptic vesicles making symmetric synaptic contacts; and (2) terminals with
      round vesicles making asymmetric synaptic contacts. The present study suggests
      the existence of propriospinal systems of ZEN neurons comprising both segmental
      and intersegmental ZEN connections and having either inhibitory or excitatory ZEN
      terminals. The ZEN neurons seem to form a vast network of terminals located
      primarily in the gray matter, but also contacting dendrites radiating into the
      white matter. Important functions of this rather massive system of ZEN terminals
      can not be deduced from our present knowledge, but the systems appear to be
      involved in both motor and sensory functions.

PMID- 11325348
TI  - In vitro effects of nicotine on mitochondrial respiration and superoxide anion
      generation.
AB  - In this study, we investigated the effects of nicotine on rat brain mitochondria.
      The polarographic studies determined the effects on the respiratory chain,
      whereas enzymatic assays and [3H]-nicotine binding allowed us to precisely
      identify its target and site of action. The measurements of oxygen consumption
      showed a significantly concentration-dependent inhibition by nicotine (EC50 was
      4.95x10(-11) M), and a maximal decrease of 23.90% at 10(-7) M. Nicotine bound to
      complex I of the respiratory chain and inhibited the NADH-Ubiquinone reductase
      activity. We also showed that nicotine and NADH were competitive on complex I.
      Effects of cotinine, the main nicotine metabolite, and nornicotine, were also
      investigated: nornicotine inhibited the mitochondrial respiration whereas
      cotinine did not. Because the complex I generates superoxide anion, we
      investigated the effects of nicotine, following NBT oxidation, and showed that
      nicotine was able to inhibit this reactive oxygen species (ROS) generation by
      15.74% with an EC50 of 2.02x10(-11) M. In conclusion, the present study shows
      that nicotine interacts with the complex I of brain mitochondrial respiratory
      chain and decreases ROS generation. This may explain a part of the beneficial and
      protective effects of nicotine in few neurodegenerative diseases, as suggested by
      many epidemiological studies.

PMID- 11325350
TI  - Reduction of voltage-operated sodium currents by the anticonvulsant drug
      sulthiame.
AB  - The effect of the sulfonamide derivative sulthiame (Ospolot) on voltage-operated
      sodium channels was investigated in acutely isolated neurons from the guinea pig
      hippocampus using the whole-cell patch-clamp technique. Sulthiame in a
      concentration of 10 microg/ml reduced the inactivating sodium currents without
      affecting potassium currents. The effect was not dependent on voltage. At
      therapeutic concentration of 1 to 10 microg/ml sodium currents were reduced by 13
      to 25% of control. Reductions of this size (induced by the specific sodium
      channel blocker tetrodotoxin or by 10 microg/ml sulthiame itself) impaired
      repetitive generation of action potentials and reduced the maximum discharge
      frequency by 20 to 40%. In summary, the anticonvulsant drug sulthiame exerts
      blocking effects on sodium channels which can be assumed to be anticonvulsant and
      to be different from the effects induced by blockade of carbonic anhydrase.

PMID- 11325351
TI  - Zn2+ differentially modulates signals from red- and short wavelength-sensitive
      cones to horizontal cells in carp retina.
AB  - The effects of Zn2+ were studied while recording intracellularly from L-type
      horizontal cells (LHCs) in the isolated, superfused carp retina. In darkness, 25
      microM Zn2+ hyperpolarized LHCs and potentiated responses of these cells to 500
      nm flashes, but decreased those to 680 nm flashes. Zn2+ did not change photopic
      electroretinographic P III responses. The differential modulation by Zn2+
      persisted when the Zn2+-induced membrane hyperpolarization was compensated by
      lowering Ca2+ concentration in the perfusate, but it was abolished in the
      presence of background illumination. Furthermore, the differential modulation no
      longer existed in the presence of bicuculline, suggesting the involvement of
      gamma-aminobutyric acid(A) (GABA(A)) receptors. We speculate that the
      differential modulation may be a consequence of multiple changes caused by Zn2+.
      Decreased glutamate release from the cone terminal by Zn2+ results in a reduction
      of cone signals. Zn2+ antagonizes GABA receptors on LHCs, leading to cone signal
      reduction. On the other hand, Zn2+ may reduce the strength of the negative
      feedback from LHCs to cones by downregulating the activity of GABA receptors on
      the cone terminal, which causes a potentiation of LHC light responses. Cone- or
      wavelength-relevance of the Zn2+-induced feedback strength change may account for
      the differential modulation.

PMID- 11325352
TI  - The frequency of cocaine administration impacts cocaine-induced receptor
      alterations.
AB  - The present study investigated the impact of dosing schedule on cocaine-induced
      receptor alterations. Rats were injected with 30 mg/kg per day of cocaine given
      either as a single injection or in two equally divided doses for 14 days. The
      effects of these two dosing regimens were compared with our previous findings
      following administration of cocaine three times daily at 1-h intervals. Using
      receptor autoradiography, twice daily injections of cocaine produced an
      upregulation of mu opioid receptors in the rostral nucleus accumbens, rostral
      caudate putamen, and layer I of the rostral cingulate cortex, whereas single
      daily injections resulted in a significant increase in the nucleus accumbens
      only. Only small insignificant increases in kappa opioid receptor densities were
      found following either once or twice daily cocaine injections, whereas three
      daily injections produced an increase in kappa receptor density in the cingulate
      cortex, nucleus accumbens, and caudate putamen. Increased dopamine D1 receptor
      binding was found in the nucleus accumbens and olfactory tubercle following twice
      daily cocaine injections, but not after single daily injections of the same total
      daily dose. These results demonstrate that the same total daily dose of cocaine
      administered in multiple small injections produces a greater effect on receptor
      regulation than a single larger injection. This suggests that the interval
      between cocaine injections is an important variable when studying the effects of
      cocaine on neurochemistry.

PMID- 11325353
TI  - Morphological features and electrophysiological properties of serotonergic and
      non-serotonergic projection neurons in the dorsal raphe nucleus. An intracellular
      recording and labeling study in rat brain slices.
AB  - The morphology and electrophysiological properties of serotonergic and non
      serotonergic projection neurons in the dorsal raphe nucleus (DRN) of the rat were
      examined in frontal brain slices. Biocytin was injected intracellularly into the
      intracellularly recorded neurons. Then the morphology of the recorded neurons was
      observed after histochemical visualization of biocytin. The recorded neurons
      extending their main axons outside the DRN were considered as projection neurons.
      Subsequently, serotonergic nature of the neurons was examined by serotonin (5-HT)
      immunohistochemistry. The general form of the dendritic trees is radiant and
      poorly branching in both 5-HT- and non-5-HT neurons. However, the dendrites of
      the 5-HT neurons were spiny, whereas those of the non-5-HT neurons were aspiny.
      The main axons of both 5-HT- and non-5-HT neurons were observed to send richly
      branching axon collaterals to the DRN, ventrolateral part of the periaqueductal
      gray and the midbrain tegmentum. In response to weak, long depolarizing current
      pulses, the 5-HT neurons displayed a slow and regular firing activity. The non-5
      HT neurons fired at higher frequencies even when stronger current was injected.
      Some other differences in electrophysiological properties were also observed
      between the 5-HT-immunoreactive spiny projection neurons and the 5-HT
      immunonegative aspiny projection neurons.

PMID- 11325354
TI  - Ion channels associated with the ectopic discharges generated after segmental
      spinal nerve injury in the rat.
AB  - In an attempt to identify important ion channels contributing to the generation
      of ectopic discharges, the present study examined the effects of ion channel
      blockers on ectopic discharges of injured sensory neurons after spinal nerve
      ligation. The main focus of the study was to examine the effect of the sodium
      channel blocker, tetrodotoxin (TTX), in order to identify important subtype(s)
      (i.e. TTX-sensitive and TTX-resistant) of sodium channels that are involved in
      ectopic discharge generation. In addition, the effects of potassium and calcium
      channel blockers were also tested for comparison with the results of previous
      studies. The dorsal root ganglion (DRG) of the injured segment was removed along
      with the dorsal root (DR) and the spinal nerve 7-14 days after spinal nerve
      ligation in the rat. The tissue was placed in an in-vitro recording chamber
      consisting of multiple compartments that were independently perfused with 35
      degrees C artificial cerebrospinal fluid (ACSF). Single unit recordings were made
      from teased DR fibers. Once a spontaneously active unit was found and
      characterized, ACSF containing a channel blocker was perfused to the DRG, the
      site where almost all ectopic discharges originate after spinal nerve ligation.
      All the recorded spontaneously active units were found to be Abeta and Adelta
      fibers (no C fibers were detected). Perfusion of the DRG with a sodium channel
      blocker (lidocaine) at a dose much less than that required to block conduction of
      action potentials, significantly inhibited ectopic discharges in all recorded
      fibers. In addition, ectopic discharges were inhibited by TTX perfused to the DRG
      at a dose much lower (average of 22.1 nM) than that required to block TTX
      resistant subtypes of sodium channels. The data suggest that TTX-sensitive sodium
      channels are likely to be involved in the generation of ectopic discharges. The
      present study also confirmed the results of previous studies on the additional
      potential roles of potassium and calcium channels, thus suggesting that multiple
      ion channels are likely to be involved in the generation of ectopic discharges.

PMID- 11325355
TI  - The influence of oxidative stress on catalase and MnSOD gene transcription in
      astrocytes.
AB  - The brain is particularly vulnerable to oxygen free radicals, which have been
      implicated in the pathology of several neurological disorders. The antioxidant
      enzyme (AOE) system of the brain may play an important role in the protection
      against such oxidative stress. We investigated the influence of oxidative stress
      on the transcription of catalase and MnSOD mRNA. Primary rat astroglial cell
      cultures were treated either with hydrogen peroxide (H2O2), as a direct mediator
      of oxidative stress, or with the redox cycling compound paraquat. Both substances
      led to an increase of catalase and MnSOD mRNA levels. To further elucidate the
      mechanisms residing behind this increase, transfection experiments were
      performed. Transient transfection of primary astroglial cells with a reporter
      plasmid containing the upstream region of the catalase gene showed a decrease in
      reporter gene activity after exposure of transfected cells to either H2O2 or
      paraquat. In contrast, transfection experiments done with reporter plasmids for
      the MnSOD upstream region resulted in an increase of reporter gene activity after
      H2O2 as well as after paraquat treatment of transfected cells. These results
      indicate transcriptional regulation of MnSOD and post-transcriptional regulation
      of catalase gene expression after oxidative stress in primary rat astrocytes.

PMID- 11325356
TI  - Deleterious effect of beta-estradiol in a rat model of transient forebrain
      ischemia.
AB  - Estrogen has demonstrated great potential as a therapeutic agent in focal
      ischemic brain injury, as exogenous beta-estradiol has proven beneficial in a
      variety of focal stroke models. In contrast, the relatively few studies of
      estrogen's efficacy in transient forebrain ischemia have produced inconsistent
      results. The present study was therefore designed to clarify estrogen's
      neuroprotective potential in selective hippocampal neuronal injury resulting from
      four-vessel occlusion in the rat. Female Wistar rats (normal, ovariectomized, or
      ovariectomized and estradiol-treated) received 5 or 10 min of ischemia. No
      differences in hippocampal cell loss were found amongst the groups with 10 min of
      ischemia. Amongst the groups with 5 min of ischemia, the mildest injury was found
      in the ovariectomized animals, which lost only 32% of their CA1 pyramidal cells.
      In comparison, mean cell losses were 54% and 49%, respectively, in intact females
      and in ovariectomized animals with estradiol replacement. Linear regression
      analysis demonstrated a highly significant relationship between cell loss and
      plasma estradiol levels. The mechanism by which exogenous and endogenous estrogen
      exacerbated the injury is unclear, as estrogen has many neuroprotective effects.
      On the other hand, many other reported effects of estrogen in hippocampal area
      CA1 might confer increased sensitivity to ischemia, either by modulating the
      excitatory effects of glutamate or by modifying the inhibitory effects of GABA.
      Determining how to modulate the various competing effects of estrogen is of both
      theoretical and practical importance, as it is now clear that one cannot assume
      that estrogen administration will always improve outcome in cerebral ischemia.

PMID- 11325357
TI  - Reversible decrease of dopamine D2 receptor density in the striatum of rats with
      acute hepatic failure.
AB  - The binding of a D2 receptor ligand, [3H]spiperone, was measured in striatal
      membranes derived from rats in which acute hepatic failure induced with
      thioacetamide (TAA) was associated with symptoms of hepatic encephalopathy (HE),
      and during recovery from HE. A 28% decrease of Bmax for the binding was measured
      in a symptomatic stage of HE, 1 day after TAA administration. The B(max) for
      [3H]spiperone binding was no longer different from control 7 days after TAA
      administration, when blood and brain biochemical correlates of HE were already
      absent. At 21 days after TAA administration, the B(max) was increased by 31%
      above the control level, consistent with other aspects of metabolic activation of
      the brain characteristic of the late recovery period from acute HE.

PMID- 11325358
TI  - Expression of 5-HT2A receptor mRNA in rat spinal dorsal horn and some nuclei of
      brainstem after peripheral inflammation.
AB  - The expression of 5-hydroxytryptamine 5-HT2A receptor mRNA was studied in the
      lumbar spinal dorsal horn, nucleus of raphe magnus (NRM), ventrolateral
      periaqueductal gray (vlPAG) and dorsal raphe nucleus (DRN) following carrageenan
      inflammation using in situ hybridization technique. The findings of this study
      demonstrated that 5-HT2A receptor mRNA was expressed with low to moderate levels
      in lumbar spinal dorsal horn, NRM, vlPAG and DRN. Following carrageenan
      inflammation, the expression of 5-HT2A receptor mRNA in ipsilateral dorsal horn,
      bilateral NRM, vlPAG and DRN was significantly increased. The peak occurred at 3
      h and then there was a clear decrease but still a substantial number of labeled
      cells at 24 h after injection of carrageenan. This result suggested that the
      synthesis of 5-HT2A receptor is enhanced in spinal dorsal horn, NRM, vlPAG and
      DRN during inflammatory pain.

PMID- 11325359
TI  - Regional and temporal progression of reactive astrocytosis in the brain of the
      myelin mutant taiep rat.
AB  - Reactive astrocytosis in taiep rats was shown by glial fibrillary acidic protein
      (GFAP) immunoreactivity measured by means of enzyme-linked immunosorbent assay
      and indirect immunofluorescence. Increased GFAP immunoreactivity was first
      observed in the brainstem of 15-day-old taiep rats and was widespread throughout
      all brain regions at 6 months of age. Characteristically, astrocytes were
      hypertrophic and displayed strong GFAP fluorescence. The pattern of these
      reactive cells may correlate with the process of dysmyelination in the taiep rat.

PMID- 11325360
TI  - Triaging patients with serious head injury: results of a simulation evaluating
      strategies to bypass hospitals without neurosurgical facilities.
AB  - OBJECTIVES: to inform the debate on whether seriously head-injured adult patients
      should be transported directly to the regional neurosurgical unit or indirectly
      after evaluation and stabilisation at the nearest hospital. DESIGN: a simulation
      model was constructed to compare triage strategies and to identify those that
      predicted the maximum survivors. In each strategy, an estimate of the patient's
      condition in the field was used to determine the receiving hospital. The model
      used data from previous publications and local ambulance service and hospital
      databases. In the absence of valid data, expert clinical estimates were made and
      subjected to sensitivity analyses. SETTING: an area in the North West Midlands of
      UK, covered by six acute hospitals including one with a regional neurosurgical
      unit. OUTCOME MEASURE: the number of survivors predicted by each triage strategy.
      RESULTS: five strategies were identified which consistently predicted the highest
      number of survivors. Compared with current policy it was predicted that in the
      North West Midlands, ten lives per year could be saved (6 per million total
      population per year). The results from sensitivity analyses did not alter these
      successful policies. CONCLUSION: the successful strategies should be considered
      as potential improvements to be introduced into clinical practice.

PMID- 11325361
TI  - Tram-related injuries in Sheffield.
AB  - The aim of this study was to identify the number of accidents and types of injury
      related to the Supertram system in Sheffield. Data was collected prospectively
      over an 18 month period, commencing in April 1994, on all patients attending the
      Accident and Emergency department at the Royal Hallamshire Hospital whose
      injuries were related to the tram system. Ninety patients were included in the
      study, 54 males and 36 females with a median age of 39 years (range 16-82),
      representing approximately 0.13% of the patients attending the department during
      the study period. Forty one patients were cyclists, twenty three pedestrians,
      twelve were motorists or motorcyclists and fourteen sustained injuries due to
      ongoing construction work. Thirty one patients sustained fractures, most commonly
      involving the upper limb/shoulder girdle (63%), with cyclists suffering 83% of
      these serious upper limb injuries. Following assessment 38 patients were
      discharged, 29 patients were referred to fracture clinic, 12 were sent for
      physiotherapy and 11 admitted to hospital. Eight patients required a total of 13
      operations during the study period. We have demonstrated a significant number of
      injuries in this study related to the tram system in Sheffield. Cyclists appear
      to be the group at highest risk, followed by pedestrians and motor vehicle users.

PMID- 11325362
TI  - Analysis of fatal pedestrian injuries in Mexico City, 1994-1997.
AB  - Currently, in Mexico City, 57% of deaths from traffic crashes are pedestrian
      injuries. The purpose of this study was to identify and analyse the magnitude,
      trends, risks, and geographic distribution of fatal pedestrian injuries during
      the period 1994-1997. A cross-sectional study design was used, based on the death
      certificates of persons who were in Mexico City during 1994-1997 and died due to
      pedestrian injuries. Mortality rates, trend analysis, standard mortality ratios
      (SMRs), and potential years of life lost index (PYLLI) were calculated by gender,
      age groups and region (these correspond to "delegations", which are political
      divisions of the city). Rates were derived according to place of occurrence and
      place of residence. A total of 3687 pedestrian fatalities were reported, and 71%
      of these were to Mexico City residents. The rate for males was 10.6/100000 with a
      slight decrease in rate from 1994 to 1997. For females, the rate was 4.0/100000,
      with an increase in rate during the same years. The present study allowed
      identification of the target population as well as regions with a high risk of
      fatal pedestrian injuries. From these data we have developed or recommended
      specific interventions for prevention and control of fatal pedestrian injuries in
      Mexico City.

PMID- 11325363
TI  - Central liver hematomas caused by mountain-bike crashes.
AB  - BACKGROUND: Mountain biking, one of the most popular sports in recent years with
      more than 10 million riders, is implicated more and more in severe bike accidents
      with complicated injuries. In addition to head injuries, which are common and
      account for most of the fatalities, we have observed an increase in liver trauma
      over the years. METHOD: Approximately 19000 bike associated accidents were
      reported in 1998 in Austria. A total of 52 patients were admitted to our trauma
      ward between 1995 and 1997 with mountain-bike associated injuries. Of the 52,
      eight presented with subcapsular hematoma of the liver sustained by falling while
      riding. In all patients, nonoperative management was successful. These injuries
      were associated with a special form of bar-ends used on the mountain-bikes. After
      a broad response from the industry, facilitated by many articles in newspapers,
      life-style magazines, radio and television stations, this type of bar end has
      nearly vanished from the market. RESULTS: As a result, in 1998, only one case of
      liver injury was observed, and from 1999 to August 2000, no such injuries have
      been reported thus far.

PMID- 11325364
TI  - How risky is early intramedullary nailing of femoral fractures in polytraumatized
      patients?
AB  - There is controversy over both the time of intervention and the technique of
      surgical stabilisation of femoral fractures in polytraumatized patients.
      Retrospective analysis of data on 55 such patients revealed that stabilisation
      within the first 24 h using locked, unreamed nails had no negative impact on the
      rate of pulmonary complications. The frequency of complications was assessed by
      comparing immediate intramedullary (IM) osteosynthesis with extramedullary
      stabilisation in patients with or without concomitant blunt thoracic trauma. Due
      to the small study population and discrepancies the size of subgroups, no
      definite statistical conclusions were possible. However, our results suggest that
      the frequency of complications is determined by the overall severity of injury
      rather than by the type of acute surgical treatment.

PMID- 11325365
TI  - Refining the indications for surgery after proximal femoral fracture.
AB  - Many patients die shortly after surgery for proximal femoral fracture. These
      patients are subjected to painful operative procedures that do not improve their
      outcome. We attempted to identify such patients with a case-controlled study of
      variables associated with death in hospital after proximal femoral fracture.
      Bronchopneumonia, ASA grade 4, heart failure and malnutrition were significantly
      associated with death but the latter two variables alone were insufficiently
      specific to justify withholding surgical treatment. However, 90% of patients with
      bronchopneumonia and those deemed unfit for anaesthesia died shortly after
      admission and their condition was not improved by active intervention. We suggest
      that it is kinder to withhold early surgery in this population.

PMID- 11325366
TI  - The treatment of impending and existing pathological femoral fractures using the
      long gamma nail.
AB  - The subtrochanteric region of the femur accounts for one-third of all
      pathological fractures requiring surgical intervention. The large forces
      occurring in this region and the possible non-occurrence of bony consolidation
      constitute a difficult problem to the trauma surgeon. The medical records and X
      rays of 25 consecutive patients treated with the long gamma nail (LGN) for
      pathological (impending or existing) fractures of the femur were analysed
      retrospectively. Our results in the use of the LGN for pathological fractures of
      the femur have been good. We recommend an aggressive approach to the early
      stabilisation of impending fractures and the use of distal locking.

PMID- 11325367
TI  - The Marchetti-Vicenzi elastic locked nail for the treatment of femoral shaft
      fractures: a review of 100 consecutive cases.
AB  - A total of 100 hundred femoral fractures in 97 patients were treated with the
      Marchetti-Vincenzi universal bundle elastic nail; six of the fractures were open.
      Closed fractures were classified according to AO and Winquist; open fractures
      were classified according to Gustilo. A total of 91 fractures united (average 12
      weeks) and six led to non-union. There were two deep and one superficial
      infections. In three cases, the secondary nails protruded from the anterior
      cortex of the femoral condyle; in two cases intraoperatively and in the third
      case 2 months postoperatively, due to severe osteoporosis. The cylindrical part
      of the nail did not fail, whereas all the secondary nails failed in one patient
      as well as one secondary nail in another patient at the level of the fracture;
      these two cases exhibited non-union. We consider the absence of distal screws the
      major advantage of this particular nail, followed by position of the entry point
      and the limited reaming. We believe that the absence of a pin guide is a
      disadvantage. The elasticity of the nail has a positive effect in certain cases
      while in other cases it acts negatively, resulting in a relatively high
      proportion of non-unions as in our series. Therefore our conclusion is that this
      nail is not appropriate for the treatment of femoral shaft fractures.

PMID- 11325368
TI  - Simultaneous ipsilateral diaphyseal fractures of the femur and tibia: treatment
      and complications.
AB  - We present our experience of intramedullary nailing (IM) and external fixation in
      the treatment of 54 patients with ipsilateral diaphyseal fractures of the femur
      and tibia. Eight femoral and 24 tibial fractures were open. They were classified
      into three groups: IM nailing of both fractures (group A, 19 patients); IM
      nailing of the femoral and external fixation of the tibial fracture (group B,
      eight patients); and external fixation of both fractures (group C, 27 patients).
      In group C (which included all but one grade III open fracture), two patients
      died and four underwent amputation. Femoral fractures treated with external
      fixation had significantly more complications and reoperations than those treated
      with IM nailing. In tibial fractures this difference was also present but not
      statistically significant. We believe that IM nailing is the method of choice for
      femoral fractures and is preferable for tibial fractures, with the exception
      probably of grade III B and C open injuries.

PMID- 11325369
TI  - Hannover Fracture Scale '98--re-evaluation and new perspectives of an established
      extremity salvage score.
AB  - OBJECTIVE: as the treatment of open fractures has improved over the years, the
      prognosis of open fractures has also changed. Thus, a re-evaluation of the
      Hannover Fracture Score (HFS), first introduced in 1983, has become necessary.
      DESIGN: retrospectively all parameters of the HFS were evaluated in 182 open
      fractures of the upper and lower extremity treated in our institution between
      June 1994 and 1996. Statistical means included multivariant analysis, ROC
      analysis, calculation of sensitivity, specificity and accuracy. Finally the HFS
      98 was established, which is characterised by eight domains with a total score
      range from 0 to 22 points and a cut off point (amputation recommended) at a score
      > or =11. This score was then prospectively applied on another 87 open long bone
      fractures, treated during July 1996 and December 1997. RESULTS: this validation
      of the HFS '98 revealed a sensitivity of 0.82 and a specificity of 0.99. In
      comparison the NISSSA and the MESS presented a lower sensitivity and same
      specificity based on the same study group. CONCLUSION: in conclusion the HFS '98
      has become a reliable extremity salvage score with a fairly high positive
      predictive value of 0.99, which is applicable for all the open long bone
      fractures regardless of their location.

PMID- 11325370
TI  - Grade III open tibial fractures: functional outcome and quality of life in
      amputees versus patients with successful reconstruction.
AB  - The purpose of this study was to assess the long-term functional outcome and the
      quality of life of patients who were treated for a (Gustilo) Grade III open
      tibial fracture. We included 43 patients with successful limb salvage (group A)
      and 21 amputees (group B). The groups were similar with regard to age, sex, and
      Injury Severity Score (ISS). The functional outcome was scored using the "Guides
      to the Evaluation of Permanent Impairment". To compare quality of life we used
      the Nottingham Health Profile (NHP), the SF-36, and a questionnaire especially
      designed for this study. The mean lower extremity impairment (AMA) of patients in
      group A was 17.6%, compared to 73.5% for patients in group B. The results with
      both NHP and SF-36 show that patients in both groups have more problems in most
      categories than a healthy reference group. With the NHP, the difference in score
      was largest for the categories of pain, mobility, energy and sleep. The SF-36
      scores correlated well with the NHP scores. No significant difference was found
      between the two groups. This type of injury has an enormous impact on every
      aspect of life--irrespective of the chosen treatment. A significant difference in
      lower extremity impairment is found between patients with a successful
      reconstruction and those who are amputees. However, the quality of life was shown
      to be the same.

PMID- 11325371
TI  - Effect of aminophylline on complete atrioventricular block with ventricular
      asystole following blunt chest trauma.

PMID- 11325372
TI  - Abdominal wall haematoma in an adolescent javelin thrower.

PMID- 11325373
TI  - Cholecystocolic fistula caused by blunt trauma.

PMID- 11325374
TI  - Metabolism and growth of juveniles of Litopenaeus vannamei: effect of salinity
      and dietary carbohydrate levels.
AB  - The present study was designed to understand how carbohydrate (CBH) and protein
      metabolism are related in the penaeid shrimp Litopenaeus vannamei. With this
      information, we obtained a comprehensive schedule of the protein-carbohydrate
      metabolism including enzymatic, energetic, and functional aspects. We used
      salinity to determine its role as a modulator of the protein-carbohydrate
      metabolism in shrimp. Two experiments were designed. The first experiment
      evaluated the effect of CBH-salinity combinations in growth and survival, and
      hemolymph glucose, protein, and ammonia levels, digestive gland glycogen, osmotic
      pressure, and glutamate dehydrogenase (GDH) of L. vannamei juveniles acclimated
      during 18 days at a salinity of 15 per thousand and 40 per thousand. The second
      experiment was done to evaluate the effect of dietary CBH level on pre- and
      postprandial oxygen consumption, ammonia excretion, and the oxygen-nitrogen ratio
      (O/N) of juvenile L. vannamei in shrimps acclimated at 40 per thousand salinity.
      We also evaluated the ability of shrimp to carbohydrate adaptation. We made
      phosphoenolpyruvate carboxykinase (PECPK) and hexokinase activity measurements
      after a change in dietary carbohydrate levels at different times during 10 days.
      The growth rate depended on the combination salinity-dietary CBH-protein level.
      The maximum growth rate was obtained in shrimps maintained at 15 per thousand
      salinity and with a diet containing low CBH and high protein. The protein in
      hemolymph is related to the dietary protein levels; high dietary protein levels
      produced a high protein concentration in hemolymph. This suggests hemolymph is
      able to store proteins after a salinity acclimation. Depending on the salinity,
      the hemolymph proteins could be used as a source of osmotic effectors or as
      metabolic energy. The O/N values obtained show that shrimp used proteins as a
      source of energy, mainly when shrimps were fed with low CBH. The role played by
      postprandial nitrogen excretion (PPNE) in apparent heat increase (AHI) (PPNE/AHI
      ratio) is lower in shrimps fed diets containing high CBH in comparison with
      shrimps fed diets containing low CBH levels. These results confirm that the
      metabolism of L. vannamei juveniles is controlled by dietary protein levels,
      affecting the processes involved in the mechanical and biochemical
      transformations of ingested food. A growth depression effect was observed in
      shrimps fed with low-CBH protein diets and maintained in 40 per thousand
      salinity. In these shrimps, the hemolymph ammonia concentration (HAC) was
      significantly higher than that observed in shrimps fed with low CBH and
      maintained in 15 per thousand salinity. That high HAC level coincided with lower
      growth rate, which suggests that this level might be toxic for juveniles of L.
      vannamei. Results obtained for GDH activity showed this enzyme regulated both HAC
      and hemolymph protein levels, with high values in shrimps fed with low CBH levels
      and maintained in 40 per thousand salinity, and lower in shrimps fed with high
      CBH and maintained in 15 per thousand salinity. These differences mean that
      shrimp with a high-gill GDH activity might waste more energy in oxidation of the
      excess proteins and amino acids, reducing the energy for growth. It was evident
      that L. vannamei can convert protein to glycogen by a gluconeogenic pathway,
      which permitted shrimp to maintain a minimum circulating glucose of 0.34 mg/ml in
      hemolymph. A high PECPK activity was observed in shrimps fed a diet containing
      low CBH level indicating that the gluconeogenic pathway is activated, as in
      vertebrates by low dietary CBH levels. After a change in diet, we observed a
      change in PEPCK; however, it was lower and seems to depend on the way of
      adaptation, because it occurred after 6 days when adapting to a high-CBH diet and
      with little change for the low-CBH diet.

PMID- 11325375
TI  - The effects of seagrass (Zostera japonica) canopy structure on associated fauna:
      a study using artificial seagrass units and sampling of natural beds.
AB  - The importance of seagrass canopy to associated fauna was assessed by comparing
      the species richness, abundance and diversity of the epi- and infaunal
      macroinvertebrate assemblages in a seagrass (Zostera japonica Ascherson and
      Graebner) bed and the adjacent unvegetated area in Hong Kong. Seagrass cover had
      significant effects on the composition and abundance of the associated fauna and
      the amount of detritus accumulated on the sediment surface. Detritus abundance
      was significantly higher in the seagrass bed, and was positively correlated with
      both the above- and belowground biomass of Z. japonica. Both the abundance and
      species richness of the epi- and infauna were significantly positively correlated
      with the belowground biomass of the seagrass and detritus standing crop.
      Macrofaunal species richness was higher (118) in the seagrass bed than the
      adjacent unvegetated areas (70), with a higher degree of similarity between the
      infauna than the epifauna of the two habitats. While all species recorded from
      the unvegetated areas were found in the seagrass bed, 48 species occurred only in
      the seagrass-covered areas. Species richness of epifauna was significantly higher
      in the seagrass bed, but there was no difference between infaunal species of the
      two habitats. On the contrary, faunal (epi- and infauna) abundance was
      significantly higher in seagrass areas. The seagrass bed also supported species
      of small tellinid bivalves previously not recorded from Hong Kong. Artificial
      seagrass units (ASUs, 0.2 m(2)) with four combinations of leaf density and leaf
      length and a control (bare sand) were placed at short distances from natural
      patches of Z. japonica. The composition, abundance and biomass of the epibenthos
      associated with the ASUs and the control were recorded after 3 months in the
      field. While species richness did not differ among the treatments, total
      abundance of epibenthos was significantly higher in the high density-long leaves
      (HL) treatment than in the control. Results of a discriminant analysis using log
      transformed abundance data suggest that the gastropod Clithon oualaniensis, the
      mussel Musculista senhousia and the crab Thalamita sp. were important species
      distinguishing the assemblages in the various treatments. All the three species
      were significantly more abundant in the HL treatment than in the low density
      short leaves (LS) treatment and the control. By contrast, there was no
      significant difference in the biomass of the epifauna, but discriminant analysis
      again separated the five treatments based on the composition of the biomass, with
      the same three species identified as the most important discriminating species.
      The species richness and abundance of the epifauna associated with the ASUs were
      similar to the adjacent unvegetated areas, but significantly lower than in the
      Zostera patches. The physical canopy structure of Z. japonica beds increased the
      abundance of the epibenthos, potentially through provision of canopy and
      indirectly through trapping of detritus.

PMID- 11325376
TI  - Light absorption by phytoplankton and the filter amplification correction: cell
      size and species effects.
AB  - Filter amplification corrections are presented for eight marine centric diatoms.
      These functions are required to correct the amplified optical path-length
      associated with the glass-fiber filter used in the measurement of phytoplankton
      absorption. Correction factors constructed from phytoplankton cultures in the
      laboratory are often applied to phytoplankton assemblages in the field. This
      study demonstrates significant differences in the filter amplification correction
      correlated to species and cell volume. This variation in the filter amplification
      correction can result in significant error in estimated absorption coefficients,
      compromising subsequent estimates of quantum yield and primary production.

PMID- 11325377
TI  - Factors influencing primary production of seagrass beds (Zostera noltii Hornem.)
      in the Thau lagoon (French Mediterranean coast).
AB  - The primary production and the respiration of Zostera noltii beds in the Thau
      lagoon were studied by means of the benthic bell jar technique. Concurrently,
      environmental data (temperature, light and nutrients) as well as morphological
      data of seagrass meadows (leaf width and height, density of shoots, above/below
      ground biomass ratio) were collected with the purpose of explaining most of the
      observed variations in metabolism. Seagrass plus epiphyte respiration rates were
      influenced mainly by the water temperature, showing a typical exponential
      response to an increase in temperature. Surprisingly, measurements of production
      rates were not related to incoming light intensities recorded at the seagrass
      canopy level. An equation frequently used for terrestrial standing crops,
      involving the leaf area index (LAI) and the characteristics of the canopy
      architecture (parameter K, depending on leaves optical and geometrical
      properties), was applied to the seagrass ecosystem in order to estimate the light
      energy actually available for the plants, i.e. the light intercepted by the
      seagrass canopy (Q(abs)). Linear relationships were then validated between gross
      production rates and calculated Q(abs) for Z. noltii beds, and the best fits were
      obtained with K values nearing 0.6, confirming the similarities between
      terrestrial graminaceae and seagrasses. A linear regression model for primary
      production is proposed, involving the calculated Q(abs), the water temperature
      and the leaf nutrient content.

PMID- 11325378
TI  - New evidence of the copepod maternal food effects on reproduction.
AB  - Failure of female reproductive capacity in the copepod Calanus helgolandicus was
      related to number and combination of the phytoplankton species in the diets. The
      maternal food effects were detectable at different levels: fecundity, oogenesis
      and hatching. Fecundity and hatching were normal with two single (ca. Isochrysis
      galbana and Prorocentrum minimum) and one mixed (Phaeodactylum
      tricornutum+Dunaliella tertiolecta+Pavlova lutherii+I. galbana+P. minimum) diets.
      With the single P. lutherii diet, fecundity decreased, but hatching remained
      optimal. The daily egg production and hatching rates decreased significantly in
      females fed the other single P. tricornutum, D. tertiolecta and mixed (P.
      tricornutum+D. tertiolecta+P. lutherii+I. galbana) diets, or starved. The
      fecundity decrease coincided with gonad atresia, which was reversible when P.
      tricornutum and P. lutherii diets were replaced by P. minimum diet. It was
      irreversible when D. tertiolecta was replaced by P. minimum, leading to female
      sterilization expressed by the deterioration of OS3 and OS2 oocytes, as a
      function of the feeding duration. We assume that atresia of female gonads was
      caused by the limitation of essential nutrients in food, such as fatty acids,
      which induced catabolism and recycling of yolk reserves and thus, maintenance of
      gonad integrity and low spawning rates. With the D. tertiolecta diet, abnormally
      high increase of ornithine concentrations in eggs showed that the ornithine
      metabolism and polyamine pathway were affected during oogenesis, leading atresia
      of oocytes to be deeply disturbed and followed up by necrosis of the gonads.

PMID- 11325379
TI  - Acute toxicity of ammonia on Litopenaeus vannamei Boone juveniles at different
      salinity levels.
AB  - Litopenaeus vannamei juveniles (total length 22+/-2.4 mm) were exposed to
      different concentrations of ammonia-N (un-ionized plus ionized ammonia as
      nitrogen), using the static renewal method at different salinity levels of 15 per
      thousand, 25 per thousand and 35 per thousand at pH 8.05 and 23 degrees C. The
      24, 48, 72, 96 h LC50 values of ammonia-N on L. vannamei juveniles were 59.72,
      40.58, 32.15, 24.39 mg l(-1) at 15 per thousand; 66.38, 48.83, 43.17, 35.4 mg l(
      1) at 25 per thousand; 68.75, 53.84, 44.93, 39.54 mg l(-1) at 35 per thousand,
      respectively. The 24, 48, 72, 96 h LC50 values of NH(3)-N (un-ionized ammonia as
      nitrogen) were 2.95, 2.00, 1.59, 1.20 mg l(-1) at 15 per thousand; 2.93, 2.16,
      1.91, 1.57 mg l(-1) at 25 per thousand; 2.78, 2.18, 1.82, 1.60 mg l(-1) at 35 per
      thousand, respectively. As the salinity decreased from 35 per thousand to 15 per
      thousand, susceptibility of ammonia-N increased by 115%, 132%, 140% and 162%
      after 24, 48, 72 and 96 h exposure, respectively. The "safety level" for rearing
      L. vannamei juveniles was estimated to be 2.44, 3.55, 3.95 mg l(-1) for ammonia-N
      and 0.12, 0.16, 0.16 mg l(-1) for NH(3)-N in 15 per thousand, 25 per thousand and
      35 per thousand, respectively.

PMID- 11325380
TI  - Diel variation of the RNA/DNA ratios in Crassostrea angulata (Lamarck) and
      Ruditapes decussatus (Linnaeus 1758) (Mollusca: Bivalvia).
AB  - The aim of this study was to investigate the effect of time of day on RNA/DNA
      ratios among fed and starved Crassostrea angulata and Ruditapes decussatus
      juveniles. Sampling to investigate the day and night condition of juveniles was
      carried out for 48 h. A highly sensitive method for nucleic acid quantification
      was applied to bivalves. The results suggest that there is some variation in
      nucleic acid quantities with the time of the day. For the two species analysed,
      the RNA/DNA ratio was particularly high during the night and was higher in the
      fed animals. The results seem to indicate that there is some endogenous rhythm in
      the production of RNA. If there are diel changes in RNA/DNA ratios, it follows
      that average RNA/DNA ratios can be unrepresentative if there is any day or night
      bias in sampling.

PMID- 11325381
TI  - Simplified method for the computation of parameters of power-law rate equations
      from time-series.
AB  - Modeling biological processes from time-series data is a resourceful procedure
      which has received much attention in the literature. For models established in
      the context of non-linear differential equations, parameter-dependent
      phenomenological tentative response functions are tested by comparing would-be
      solutions of those models to the experimental time-series. Those values of the
      parameters for which a tested solution is a best fit are then retained. It is
      done with the help of some appropriate optimization algorithm which simplifies
      the searching procedure within the range of variability of the parameters that
      are to be estimated. The procedure works well in problems with a small number of
      adjustable parameters or/and with narrow searching ranges. However, it may start
      to be problematic for models with a large number of problem parameters inasmuch
      as convergence to the best fit is not necessarily ensured. In this case, a
      reduction in size of the parameter estimation problem must be undertaken. We
      presently address this issue by proposing a systematic procedure that does so in
      problems in which the system's response to a sufficiently small pulse
      perturbation of steady-state can be obtained. The response is then assumed to be
      a solution of the linearized equations, the Jacobian of which can be retrieved by
      a simple multilinear regression. The calculated n(2) Jacobian entries provide as
      many relationships among problem parameters, thus cutting substantially the size
      of the starting problem. After this preliminary treatment is applied, only (kappa
      n(2)) of the initial kappa adjustable parameters are left for evaluation by means
      of a non-linear optimization procedure. The benefits of the present variant are
      both in economy of computation and in accuracy in determining the parameter
      values. The performance of the method is established under different
      circumstances. It is illustrated in the context of power-law rates, although this
      does not preclude its applicability to more general functional responses.

PMID- 11325382
TI  - Attractor reconstruction for non-linear systems: a methodological note.
AB  - Attractor reconstruction is an important step in the process of making
      predictions for non-linear time-series and in the computation of certain
      invariant quantities used to characterize the dynamics of such series. The
      utility of computed predictions and invariant quantities is dependent on the
      accuracy of attractor reconstruction, which in turn is determined by the methods
      used in the reconstruction process. This paper suggests methods by which the
      delay and embedding dimension may be selected for a typical delay coordinate
      reconstruction. A comparison is drawn between the use of the autocorrelation
      function and mutual information in quantifying the delay. In addition, a false
      nearest neighbor (FNN) approach is used in minimizing the number of delay vectors
      needed. Results highlight the need for an accurate reconstruction in the
      computation of the Lyapunov spectrum and in prediction algorithms.

PMID- 11325383
TI  - Resource allocation for epidemic control over short time horizons.
AB  - We present a model for allocation of epidemic control resources among a set of
      interventions. We assume that the epidemic is modeled by a general compartmental
      epidemic model, and that interventions change one or more of the parameters that
      describe the epidemic. Associated with each intervention is a 'production
      function' that relates the amount invested in the intervention to values of
      parameters in the epidemic model. The goal is to maximize quality-adjusted life
      years gained or the number of new infections averted over a fixed time horizon,
      subject to a budget constraint. Unlike previous models, our model allows for
      interacting populations and non-linear interacting production functions and does
      not require a long time horizon. We show that an analytical solution to the model
      may be difficult or impossible to derive, even for simple cases. Therefore, we
      derive a method of approximating the objective functions. We use the
      approximations to gain insight into the optimal resource allocation for three
      problem instances. We also develop heuristics for solving the general resource
      allocation problem. We present results of numerical studies using our
      approximations and heuristics. Finally, we discuss implications and applications
      of this work.

PMID- 11325384
TI  - Modeling and analysis of a predator-prey model with disease in the prey.
AB  - A system of retarded functional differential equations is proposed as a predator
      prey model with disease in the prey. Mathematical analyses of the model equations
      with regard to invariance of non-negativity, boundedness of solutions, nature of
      equilibria, permanence and global stability are analyzed. If the coefficient in
      conversing prey into predator k=k(0) is constant (independent of delay tau;,
      gestation period), we show that positive equilibrium is locally asymptotically
      stable when time delay tau; is suitable small, while a loss of stability by a
      Hopf bifurcation can occur as the delay increases. If k=k(0)e(-dtau;) (d is the
      death rate of predator), numerical simulation suggests that time delay has both
      destabilizing and stabilizing effects, that is, positive equilibrium, if it
      exists, will become stable again for large time delay. A concluding discussion is
      then presented.

PMID- 11325385
TI  - Speeds of invasion in a model with strong or weak Allee effects.
AB  - We study an invasion model based on a reaction-diffusion equation with an Allee
      effect. We use a special, piecewise-linear, population growth rate. This function
      allows us to obtain traveling wave solutions and to compute wave speeds for a
      full range of Allee effects, including weak Allee effects. Some investigators
      claim that linearization fails to give the correct speed of invasion if there is
      an Allee effect. We show that the minimum speed for a sufficiently weak Allee
      may, in fact, be the same as that derived by means of linearization.

PMID- 11325386
TI  - A computer model to simulate family history of breast/ovarian cancer in BRCA1
      mutation carriers.
AB  - The BRCA1 gene and its relationship to family history of breast/ovarian cancer
      are difficult to study in a population because of practical and ethical issues.
      The paucity of information on BRCA1 in the general population was a major theme
      in a recent review of genetic testing in Canada. We develop a simulation model to
      mimic genetic inheritance and cancer incidence in the family of someone with a
      germline BRCA1 mutation. Given someone's age and family structure, our model
      simulates his or her family history in three steps: (1) determine which family
      members have the mutation, (2) determine the ages of family members and (3)
      determine which family members have breast/ovarian cancer. Each step involves
      random variation. Some parameters in our model are estimated using local (British
      Columbia, Canada) population data. The breast/ovarian cancer risk associated with
      BRCA1 mutations is estimated using values published in the literature. An example
      is provided to illustrate the model's application. The model incorporates results
      from genetics, demography and epidemiology, but requires several additional
      assumptions. Research to address these assumptions is recommended.

PMID- 11325387
TI  - Antagonism at 5-HT(2A) receptors potentiates the effect of haloperidol in a
      conditioned avoidance response task in rats.
AB  - High affinity for serotonin-2A (5-HT(2A)) over dopamine (DA) D(2) receptors is a
      leading hypothesis for clozapine's favorable therapeutic profile. Recent
      preclinical studies also indicate that a sufficient antipsychotic effect might be
      obtained by a combined high 5-HT(2A)/low D(2) receptor blockade. Thus, addition
      of a 5-HT(2A) receptor antagonist to an ineffective dose of a D(2) receptor
      antagonist produces a robust antipsychotic-like effect in the conditioned
      avoidance response (CAR) test. Electrophysiological and biochemical studies also
      show that 5-HT(2A) receptor antagonists can confer an atypical (clozapine-like)
      profile on a D(2) receptor antagonist. Improved therapeutic efficacy by
      adjunctive 5-HT(2A) receptor antagonist treatment to a traditional D(2) receptor
      blocking regimen has been suggested. However, the ability of 5-HT(2A) receptor
      blockade to protect against, or ameliorate, parkinsonian symptoms still remains
      unclear. Using the CAR and the catalepsy (CAT) tests as indices for antipsychotic
      activity and extrapyramidal side effect (EPS) liability, respectively, the
      effects of the selective 5-HT(2A) receptor antagonist MDL 100,907 in combination
      with the DA D(2) receptor antagonists haloperidol or raclopride were studied in
      rats. Haloperidol (0.025 or 0.1 mg/kg sc, -30 min) produced a dose-dependent
      suppression of CAR. Pretreatment with MDL 100,907 (0.5, 1.0, or 1.5 mg/kg sc; -60
      min) enhanced and prolonged the haloperidol-induced suppression of CAR without
      escape failures. MDL 100,907 (1 mg/kg sc, -60 min) had no effect on CAT when
      coadministered with ineffective doses of raclopride. Raclopride (1 mg/kg sc, -30
      min) alone produced a submaximal cataleptic response that was significantly
      enhanced by pretreatment with MDL 100,907. The present results confirm and extend
      previous results by showing that 5-HT(2A) receptor blockade can enhance the
      antipsychotic-like effects of a very low dose of a commonly used traditional
      antipsychotic. 5-HT(2A) receptor blockade does not, however, prevent EPS (CAT).
      The therapeutic advantage of this combination might, therefore, operate within a
      fairly narrow window.

PMID- 11325388
TI  - Antagonism of the discriminative stimulus effects of (+)-7-OH-DPAT by remoxipride
      but not PNU-99194A.
AB  - The dopamine (DA) agonist 7-hydroxy-N,N-di-n-propyl-2-amino-tetralin (7-OH-DPAT)
      has been used extensively as a tool to investigate the role of DA D(3) receptors
      in the reinforcing and discriminative stimulus properties of psychostimulant
      drugs. The present study examined the relative importance of D(3) vs. D(2)
      receptor actions in the discriminative stimulus effects of (+)-7-OH-DPAT (0.03
      mg/kg, sc) in 16 male Sprague-Dawley rats trained to discriminate this compound
      from saline in a two-lever, water-reinforced operant procedure under a FR 20
      schedule. Stimulus generalization and antagonism tests were conducted with
      cocaine and with various selective D(2) and D(3) receptor ligands. In contrast to
      previous findings that (+)-7-OH-DPAT substitutes for cocaine, the present results
      demonstrated that cocaine does not produce stimulus generalization in animals
      trained to discriminate (+)-7-OH-DPAT. Although two D(3)-preferring agonists, PD
      128907 and pramipexole, produced complete stimulus generalization to the training
      drug, two highly selective D(3) antagonists (PNU-99194A, PD 152255) failed to
      block the discriminative stimulus effects of (+)-7-OH-DPAT. However, the D(2)
      antagonist remoxipride (3.0 mg/kg) produced a rightward shift in the (+)-7-OH
      DPAT dose-response curve. These findings suggest that D(2) receptors are
      critically involved in mediating the cue properties of (+)-7-OH-DPAT. However,
      alternative interpretations that PNU-99194A is not entirely D(3) receptor
      selective should also be considered.

PMID- 11325389
TI  - Withdrawal from alcohol in withdrawal seizure-prone and -resistant mice: evidence
      for enkephalin resistance.
AB  - Methionine enkephalin (Met-enkephalin) functions as an endogenous anticonvulsant.
      Peptide transport system-1 (PTS-1) is an important regulator of Met-enkephalin
      levels in brain and transports the peptide from brain to blood. In outbred mice,
      alcohol dependence is associated with decreased PTS-1 activity and increased
      levels of Met-enkephalin. In contrast, alcohol withdrawal is associated with
      recovery of PTS-1 activity, decreased levels of Met-enkephalin, and seizures. In
      this study, we examined the PTS-1/Met-enkephalin system in two replicates of
      withdrawal seizure-resistant (WSR) and withdrawal seizure-prone (WSP) mouse
      lines. We measured levels of preproenkephalin (PPE) mRNA and Met-enkephalin
      peptide in brain and the activity of PTS-1 during alcohol-naive, -dependent, and 
      withdrawal states. In alcohol-naive animals, Met-enkephalin levels were higher in
      WSP than in WSR mice. In alcohol-withdrawal animals, Met-enkephalin levels
      remained elevated in WSP mice, whereas they increased in WSR mice. Peptide levels
      were unrelated to levels of PPE mRNA or activity of PTS-1. Factorial analysis
      showed that proneness to seizures was genetically linked to Met-enkephalin levels
      in alcohol-naive, -dependent, and -withdrawing mice but not to mRNA levels or PTS
      1 activity. Overall, these results may be explained by resistance to enkephalin
      in WSP mice and suggest that the dysregulation of the PTS-1/Met-enkephalin system
      contributes to susceptibility to seizures in WSP mice.

PMID- 11325390
TI  - Spatial learning and morphine-rewarded place preference negatively correlates in
      mice.
AB  - Accumulating evidence has indicated that there might exist some correlation
      between opiate reward and certain kinds of learning and memory processes. The
      present study attempted to investigate the correlation between individual
      differences in morphine reward and capacities in spatial learning and spontaneous
      alternation. In the present studies, good-response (GR) and poor-response (PR)
      mice were respectively selected according to their performance in a spatial
      learning test involving the Morris water maze or in a spontaneous alternation
      task using the Y-maze. In a place preference conditioning procedure, morphine
      (3.0 mg/kg) produced significant conditioned place preference (CPP) in both GR
      and PR mice selected by using either the Morris water maze or the Y-maze. The PR
      mice selected with the Morris water maze showed significantly more CPP induced by
      morphine than the GR mice. However, no detectable difference was observed in
      morphine-induced CPP between the GR and PR mice selected with the Y-maze. These
      results suggested that the variation in morphine-induced CPP in mice is somehow
      differentially related to that of spatial learning but unlikely to that of
      spontaneous alternation.

PMID- 11325391
TI  - Schedule control of quantal and graded dose-effect curves in a drug-drug-saline
      discrimination.
AB  - Pigeons were trained to discriminate among 5 mg/kg pentobarbital, 5 mg/kg
      morphine, and saline when responding was maintained under fixed-interval (FI) or
      fixed-ratio (FR) reinforcement schedules. After the discrimination was
      established, other drugs were substituted for the training drugs. After low doses
      of pentobarbital and chlordiazepoxide, responding shifted from the saline key to
      the pentobarbital key under both FR and FI schedules. After low doses of morphine
      and methadone, responding shifted from the saline key to the morphine key under
      both reinforcement schedules. After all doses of d-amphetamine, responding
      occurred largely on the saline key under both schedules. Responding also was
      confined largely to the saline key after phencyclidine administration under the
      FR schedule, but under the FI schedule, responding shifted from the saline key to
      the pentobarbital key at high doses of phencyclidine. When responding was
      maintained under the FR schedule, the dose-response curves for drugs that
      generalized to the training drugs were quantal in shape, while under the FI
      schedule, the dose-response curves for drugs that generalized to the training
      drugs were graded. These data extend observations that FR schedules generate
      quantal dose-response curves, and FI schedules generate graded dose-response
      curves to complex three-key drug discriminations.

PMID- 11325392
TI  - Testing and analytical procedures for laboratory studies involving nonresponders
      during a limited observation period: an illustration using male sexual behavior
      in rats.
AB  - In many laboratory studies, a subpopulation of subjects fails to exhibit the
      response under investigation during the period of observation. For example,
      within any population of male rats, there is significant variation in the
      expression of sexual behavior in the presence of a receptive female. Some males
      may never display the full sequence of behaviors leading to ejaculation within
      the typical time frame of the testing session, with the resulting lack of
      behavioral response presenting problems in the analysis of the data. Conventional
      strategies range from screening such males from the study or dropping them from
      the analysis to constructing new variables based on estimates from existing
      parameters or increasing the length of the test session to capture sexual
      responses in a greater portion of males. Herein, we present an alternative
      strategy for analyzing data where outcomes are absent due to the limited
      observation period. Survival regression analysis enables inclusion of all
      subjects in the analysis whether or not they have shown the behavior of interest.
      Use of such a strategy not only has potential to reveal new results but also
      guards against bias from excluding nonresponders from the study or dropping more
      males from one experimental condition than another. Furthermore, this procedure
      can be helpful in generating the conditional probability (increase, decrease, or
      constant) of the response with the passage of time based on the hazard function
      and in estimating parameters for establishing an optimal behavioral test length
      for future studies.

PMID- 11325393
TI  - Dopamine antagonism attenuates the unconditioned incentive value of estrous
      female cues.
AB  - The role of dopaminergic transmission in the incentive-motivational processes
      involved in the generation of male sexual behavior was examined. Three groups of
      sexually naive Long-Evans male rats traversed a straight alley for one of three
      goalbox targets: an empty goalbox, a nonestrous female, or an estrous female. A
      Plexiglas partition within the goalbox allowed for the perception of visual,
      auditory, and olfactory cues, but prevented physical contact. Baseline run times
      revealed that subjects returned to the goalbox significantly faster for an
      estrous female than for a nonestrous female, replicating our earlier work on the
      inherent incentive value of primary female cues. When subjects were then
      pretreated with the dopamine receptor antagonist, haloperidol (0.0, 0.075, or
      0.15 mg/kg), they expressed decreased sexual motivation as reflected by increased
      run times for estrous female targets. Subjects' run times for the empty goalbox
      condition were unaffected by haloperidol, suggesting that the drug did not
      reliably impair motoric capacity. Results support the contention that central
      dopaminergic systems are involved in the regulation of the positive,
      unconditioned incentive value of estrous female cues.

PMID- 11325394
TI  - Differential effects of 7-OH-DPAT on the development of behavioral sensitization
      to apomorphine and cocaine.
AB  - The primary objective of this study was to determine whether concurrent
      treatments with a low dose of the dopamine D(3)-preferring receptor agonist 7-OH
      DPAT would attenuate the development of behavioral sensitization to the indirect
      dopamine receptor agonist, cocaine, or the direct dopamine receptor agonist,
      apomorphine. In two experiments, male Wistar rats (250-350 g) were given seven
      daily injections of 7-OH-DPAT (0.05 mg/kg sc) or vehicle in combination with
      either cocaine (15 mg/kg ip), apomorphine (1.0 mg/kg sc), or vehicle. After the
      injections, the rats were tested for activity in photocell arenas for 40 min, and
      three measures of motor behavior (distance traveled, rearing, and stereotypy)
      were recorded at 10-min intervals. A total of 24 h after the last preexposure
      session, all rats were given a challenge injection of either cocaine (10.0 mg/kg
      ip, Experiment 1) or apomorphine (1.0 mg/kg sc, Experiment 2) and tested for
      activity. Major findings were as follows: (a) 7-OH-DPAT treatments alone
      suppressed all measures of locomotor activity and did not affect subsequent
      behavioral sensitivity to either cocaine or apomorphine; (b) cocaine treatments
      acutely increased all measures of activity, and repeated treatments produced
      behavioral sensitization to the horizontal locomotor-activating effects of
      cocaine; (c) apomorphine treatments alone increased horizontal activity and
      stereotypy but completely abolished rearing behavior; (d) like cocaine, repeated
      treatments with apomorphine induced behavioral sensitization; (e) concurrent
      treatments of 7-OH-DPAT with cocaine acutely attenuated cocaine-induced increases
      in motor behavior but enhanced the development of behavioral sensitization to
      cocaine; and (f) concurrent 7-OH-DPAT treatments did not significantly affect
      either the acute or chronic effects of apomorphine. It is evident from these
      results that concurrent treatment with 7-OH-DPAT does not block the development
      of behavioral sensitization to either cocaine or apomorphine. Moreover, the
      differential acute and chronic effects of 7-OH-DPAT on cocaine- and apomorphine
      induced hyperactivity appear to be mediated by dopamine autoreceptor stimulation.

PMID- 11325395
TI  - Discriminative stimulus properties of indorenate in a conditioned taste aversion
      paradigm.
AB  - Indorenate (5-methoxytryptamine beta-methylcarboxylate, INDO) is a serotonin (5
      hydroxytryptamine, 5-HT) agonist that has affinity for 5-HT(1A/1B/2C) receptors.
      It possesses anxiolytic and antihypertensive actions mediated by 5-HT(1A)
      receptors and anorectic activity mediated by 5-HT(2C/1B) receptors. This study
      examined whether INDO may exert discriminative control using a conditioned taste
      aversion (CTA) paradigm, and whether differential participation of 5-HT receptor
      subtypes may be involved in its cue. Male Wistar rats trained to drink their
      daily water in a 30-min period were trained to discriminate INDO from saline. One
      group received the intraperitoneal administration of INDO (10.0 mg/kg) before
      saccharin-LiCl pairings; on alternate days, rats received saline before the
      saccharin-saline pairings (Group D(+)S(-)). The other group had the contingencies
      reversed (i.e., the administration of INDO preceded saccharin-saline pairings:
      Group D(-)S(+)). In two-bottle generalization tests (one bottle containing
      saccharin, the other plain water), the preference for saccharin was evaluated
      after different doses of INDO, [3H]-8-hydroxy-2-(di-N-propylamino)tetralin (8-OH
      DPAT) (5-HT(1A)), buspirone (5-HT(1A)), RU24969 (5-HT(1A/1B)), TFMPP (5
      HT(1B/2C)), MK212 (5-HT(2C)), alpha-Me-5-HT (5-HT(2C/2A)), 2-Me-5-HT (5-HT(3))
      and cisapride (5-HT(4)). The results showed that INDO, RU24969, TFMPP, alpha-Me-5
      HT and MK 212 produced a dose-dependent generalization; 8-OH-DPAT and buspirone
      produced only partial generalization, while 2-Me-5-HT and cisapride did not
      produce generalization. The results indicate that INDO administration may exert
      discriminative control over saccharin preference mediated mainly by 5-HT(1B/2C)
      receptors, but with an important contribution of 5-HT(1A) receptors.

PMID- 11325396
TI  - Antidepressant, anxiogenic, and antinociceptive properties of levofloxacin in
      rats and mice.
AB  - Levofloxacin, an optically active isomer of ofloxacin, is a fluorinated quinolone
      with a broad spectrum of antibacterial activity. Fluoroquinolones have been used
      for the treatment of bacterial infections for many years. Although they were
      considered as relatively safe drugs, various adverse effects have recently been
      reported along with increase in the usage of new-generation fluoroquinolones. In
      the present study, some of the central nervous system (CNS)-related side effects
      of levofloxacin were clarified in animals. Our results suggested that:
      levofloxacin (10-20-40 mg/kg i.p.) had no depression-like effect in the forced
      swimming test (FST) in rats; exerted anxiety-like effect in the elevated plus
      maze test in rats; did not alter the locomotor activity in rats; had no apparent
      effect on sleep latency but shortened the sleeping time on pentobarbital sleeping
      time in mice; and showed analgesic activity in acetic acid writhing and hot plate
      test in mice.

PMID- 11325397
TI  - Effects of cerestat and NBQX on functional and morphological outcomes in rat
      focal cerebral ischemia.
AB  - This study investigated the ability of NBQX, an AMPA receptor antagonist, and
      cerestat, a NMDA receptor antagonist, to counteract neurological deficits and
      morphological damage induced by permanent occlusion of the left middle cerebral
      artery (MCAO model) in the rat. NBQX (3, 10, and 30 mg/kg, ip) injected at 10,
      60, and 120 min postocclusion did not reduce the volume of infarct in the MCAO
      model of cerebral ischemia and had marginal effects on sensory dysfunctions
      (vibrissae stimulation and body proprioception) and no effects on motor
      dysfunctions (forelimb flexion and footfault test). Conversely, cerestat (0.3, 1,
      and 3 mg/kg, sc) injected at 10 and 120 min postocclusion significantly reduced
      the ischemic volume at the dose of 1 mg/kg, and, at the same dose, significantly
      attenuated behavioural deficits in the body proprioception and in the forelimb
      flexion tests.

PMID- 11325398
TI  - Conditioned stimulus preference after acetaldehyde but not ethanol injections.
AB  - Acetaldehyde, the first ethanol metabolite, has been suggested to mediate some of
      the behavioral effects of ethanol and particularly its reinforcing properties,
      although this later hypothesis remains extremely controversial. While several
      studies demonstrated the reinforcing effects of brain acetaldehyde, blood
      acetaldehyde accumulation is believed to be primarily aversive. In the present
      study, a conditioned reinforcement procedure has been used to investigate the
      reinforcing and/or aversive effects of intraperitoneal injections of both
      acetaldehyde and ethanol in Wistar rats. An olfactory stimulus was paired with
      daily injections of either ethanol (0, 0.25, 0.5, 1 and 2 g/kg) or acetaldehyde
      (0, 10, 20, 100 and 150 mg/kg). After eight conditioning sessions, all rats were
      tested for their stimulus preference or aversion. The results show that
      conditioning with small, 0.25 and 0.5 g/kg, ethanol doses induced neither
      preference nor aversion for the olfactory cue. In contrast, higher ethanol doses
      (1.0 and 2.0 g/kg) resulted in significant stimulus aversions. Acetaldehyde
      conditioning led to a biphasic stimulus preference, with a maximal preference
      around 20 mg/kg acetaldehyde. No evidence of aversive effects was found with
      increasing doses of acetaldehyde, even with concentrations close to the lethal
      limit. The present study clearly shows that systemic acetaldehyde injections
      induced significant stimulus preferences. This suggests that acetaldehyde may be,
      at least in part, responsible for the reinforcing effects of alcohol intake.

PMID- 11325399
TI  - Intravenous cocaine increases plasma epinephrine and norepinephrine in humans.
AB  - Cocaine has been shown to activate the sympathoadrenal system in both animal and
      human studies. Controlled human studies have found inconclusive results regarding
      whether acute cocaine treatment elevates plasma epinephrine and norepinephrine
      concentrations. The purpose of this study was to investigate whether commonly
      abused doses of cocaine increase plasma epinephrine and norepinephrine
      concentrations in humans, in a double-blind, placebo-controlled study. Five male
      cocaine users were given an intravenous injection of 0.46 mg/kg dose of cocaine
      or placebo, on two consecutive days. Plasma epinephrine and norepinephrine
      concentrations were significantly increased in response to cocaine injection
      compared to placebo. Peak plasma epinephrine and norepinephrine concentrations
      were reached 3 and 12 min after cocaine injection, respectively. While changes in
      epinephrine levels following cocaine were correlated with systolic blood pressure
      and heart rate changes, changes in plasma norepinephrine were correlated with
      diastolic blood pressure and heart rate changes following cocaine administration.
      These results suggest that plasma epinephrine and norepinephrine can be used as a
      measure for cocaine induced sympathoadrenal system activation.

PMID- 11325400
TI  - Effects of dopamine receptor antagonists on ongoing maternal behavior in rats.
AB  - The effects of different peripheral doses of four dopamine (DA) receptor
      antagonists on general activity and maternal behavior were examined in lactating
      female rats. Administration of the classic D1-like and D2-like DA receptor
      blocker haloperidol (0.1 and 0.05 mg/kg) disrupted pup retrieval and nest
      building behaviors and reduced motor activity. Pimozide (0.5 and 0.2 mg/kg),
      which has more affinity for DA D2-like receptors, mildly disrupted pup retrieval
      while showing no significant influence on open-field behaviors. The putative DA
      D(4) receptor blocker, clozapine (1.5 and 1.0 mg/kg) reduced motor activity
      significantly, while only 1.0 mg/kg dose significantly decreased percent of rats
      displaying nest building. The DA D1-like receptor blocker SKF-83566 (0.2 and 0.1
      mg/kg) significantly reduced pup retrieval, nest building and motor activity.
      These results suggest a role for DA receptors in ongoing maternal behavior that
      correlates directly with general activity.

PMID- 11325401
TI  - Stimulus properties of 7-OH-DPAT versus auto- and postsynaptic receptor-specific
      doses of quinpirole.
AB  - The five types of dopamine (DA) receptor subtypes have been grouped into two
      families, the D(1)-like (D(1) and D(5) receptors) and D(2)-like (D(2), D(3), and
      D(4) receptors). Experimental evidence indicates that D(2)-like receptors can be
      located either presynaptically, where they modulate the synthesis and release of
      DA, or postsynaptically. Controversy exists, however, over the precise location
      and role of the D(3) subtype of DA receptor. To investigate this issue, rats were
      trained using standard operant drug discrimination procedures to discriminate
      0.10 mg/kg of the putatively D(3) receptor-preferring agonist R(+)-7-hydroxy-N,N,
      di-n-propyl-2-aminotetralin (7-OH-DPAT) from saline. Patterns of generalization
      to D-amphetamine, AMPT, and SCH 23390 indicated a presynaptic action of 7-OH
      DPAT, while apomorphine generalization patterns suggested a postsynaptic action;
      quinpirole generalization suggested both a pre- and postsynaptic action of 7-OH
      DPAT. The ability of spiperone, eticlopride, SCH 23390, and UH 232 to partially
      antagonize the 7-OH-DPAT stimulus attests to its lack of receptor subtype
      specificity. These results suggest both pre- and postsynaptic actions of 7-OH
      DPAT along with a lack of specificity of the various pharmacological compounds
      for the D(3) receptor.

PMID- 11325402
TI  - Increased sensitivity of dopamine systems following reproductive experience in
      rats.
AB  - Several studies have suggested that alterations in forebrain dopamine activity
      during the postpartum period may result in the onset of postpartum psychosis in
      women [J. Psychosom. Obstet. Gynecol. 19 (1998) 104; Prog. Neuro-Psychopharmacol.
      Biol. Psychiatry 17 (1993) 571; J. Clin. Psychiatry 51 (1990) 365.]. The present
      study investigated whether increased dopamine activity in these forebrain regions
      is a normal consequence of reproductive experience in rodents. Both intact and
      ovariectomized parous and nulliparous females were tested for their responses to
      the dopamine agonist apomorphine using two behavioral measures, prepulse
      inhibition (PPI) and oral stereotypy. In addition, dopamine and DOPAC levels were
      measured in tissue from the striatum and nucleus accumbens together with
      circulating plasma prolactin levels. The results of the behavioral studies
      demonstrate an increased response to apomorphine in parous females. Parous
      subjects also had increased levels of dopamine and DOPAC in striatal tissue and
      lower levels of circulating prolactin. Ovariectomy in nulliparous females
      resulted in a potentiated response to apomorphine with regard to the disruption
      of PPI, as well as a significant decrease in the plasma prolactin levels, as
      compared with intact nulliparous females. These data suggest that increased
      dopamine activity in forebrain regions occurs as a consequence of parity, which
      persists for a minimum of several weeks postpartum. These findings support the
      hypothesis that increased dopamine sensitivity in forebrain dopamine regions may
      be one potential mechanism underlying the development of postpartum psychosis in
      women.

PMID- 11325403
TI  - Mice performance on the staircase test following acute ethanol administration.
AB  - This study examined the effect of acute ethanol administration as compared to
      diazepam on the number of rearing events and the number of steps ascended in the
      mouse staircase test, an animal model sensitive to benzodiazepines. Acute ethanol
      administration, similar to acute diazepam administration, reduces rearing (at
      doses that do not reduce climbing) in the staircase test. This effect of acute
      ethanol administration is insensitive to the benzodiazepine antagonist flumazenil
      and is not consistently counteracted by the partial inverse agonist Ro15-4513. It
      seems that the mouse staircase test is an efficient paradigm for studying agents
      active at the gamma-aminobutyric acid (GABA(A)) receptor complex, including
      ethanol.

PMID- 11325404
TI  - Lipopolysaccharide induces memory-processing deficits in day-old chicks.
AB  - Recent evidence has demonstrated that immune activation can result in cognitive
      deficits due to the actions of the proinflammatory cytokines. These series of
      studies examined the effects of peripheral administration of lipopolysaccharide
      (LPS) on the memory processes of day-old chicks trained on a single-trial passive
      avoidance task. LPS impaired performance in a dose- and time-dependent manner.
      Maximal impairment was produced by a dose of 2.5-mg/kg LPS administered 60 min
      prior to training. Retention tests revealed that deficits in memory processing
      appeared between 10 and 20 min posttraining. These results demonstrate an
      inhibitory effect of LPS on memory processing at the transition point from short
      term memory to intermediate-term memory.

PMID- 11325405
TI  - Facilitation of latent inhibition by the atypical antipsychotic risperidone.
AB  - The action of the atypical antipsychotic risperidone on latent inhibition (LI),
      an animal model of schizophrenia, was investigated. The parameters of the
      procedure were set at values insufficient to generate LI in control rats. On the
      first day, rats administered 0.5, 1.0, or 2.0 mg/kg ip risperidone or vehicle
      were preexposed (PE) to 10 tone presentations. On the second day, they were again
      injected with drug or vehicle and then submitted to two conditioned stimulus (CS;
      tone)-unconditioned stimulus (US; shock) pairings. On the third day, suppression
      of their drinking response under the CS was measured. Nonpreexposed (NPE) animals
      were submitted to the same procedure except for the tone preexposure. On the
      suppression test, LI was not observed in control rats as well as in animals given
      0.5 mg/kg risperidone. Animals given 1.0 and 2.0 mg risperidone, however,
      displayed an LI effect. The facilitation of LI by risperidone gives additional
      support to the LI paradigm as an animal model of schizophrenia.

PMID- 11325406
TI  - Reversal of morphine-induced memory impairment in mice by withdrawal in Morris
      water maze: possible involvement of cholinergic system.
AB  - The effects of morphine and morphine withdrawal on memory performance were
      examined in mice by using Morris water maze task. Morphine-induced memory
      impairment at the doses of 5 and 10 mg/kg recovered after repeated
      administration. Oxotremorine, a muscarinic receptor agonist, at the dose of 0.1
      mg/kg ip, and physostigmine, a cholinesterase inhibitor, at the dose of 0.1 mg/kg
      ip, significantly antagonized morphine (10 mg/kg sc)-induced memory impairment in
      mice. Furthermore, repeated naloxone (0.5 mg/kg ip) attenuated scopolamine (0.2
      mg/kg ip)-induced memory impairment. By using escalating doses of morphine for 13
      days, morphine-induced memory impairment was continuously maintained. When
      withdrawal was precipitated by naloxone (5 mg/kg ip), or administration of
      oxotremorine (0.1 and 0.2 mg/kg ip) or physostigmine (0.05 and 0.1 mg/kg ip), the
      impairment was completely reversed. These results suggest that morphine-induced
      memory impairment could be partially due to the inhibition of the central
      cholinergic activity.

PMID- 11325407
TI  - Exposure to ethanol and nicotine during the brain growth spurt: spatial DMP
      performance in male rats.
AB  - Male Long-Evans rats were reared artificially and, using a 2x2 design, were
      exposed from postnatal days (PD) 6-9 to ethanol (ET: 6.5 g kg(-1) day(-1) "binge"
      exposure) and/or nicotine bitartrate (NIC: 6 mg kg(-1) day(-1) continuous
      exposure) via gastrostomy tubes. Controls were administered maltose-dextrin in
      amounts isocaloric to ET and/or sodium bitartrate. A fifth suckled-control group
      was reared normally. NIC accelerated eye opening on PD 14; whereas ET delayed eye
      opening and hindlimb support on PD 16. Beginning in postnatal week 7, rats were
      tested on a spatial delayed matching-to-place (DMP) version of the Morris water
      maze, which entailed a series of problems, each consisting of search and recall
      trials, that required the rats to use extra-maze cues to locate a hidden escape
      platform. In Phase 1 of testing, the ET-exposed groups were impaired in the
      recall trials, but there was no effect of NIC. A longer encoding time (45 vs. 10
      s) improved performance across all groups. In contrast, acute administration of
      NIC (0.1 mg/kg ip) immediately prior to testing in Phase 2 failed to improve
      performance in any group. In conclusion, these results confirm previous findings
      of impaired spatial DMP-task performance in ET-exposed rats and further suggest
      that these memory deficits are amenable to amelioration.

PMID- 11325408
TI  - 3-Methyl-5-hydroxy-5-trichloromethyl-1H-1-pyrazolcarboxyamide induces
      antinociception.
AB  - The antinociceptive action of a novel pyrazole-derived compound, 3-methyl-5
      hydroxy-5-trichloromethyl-1H-1-pyrazolcarboxyamide (MPCA) was evaluated using the
      formalin and tail-immersion tests in mice. Anti-inflammatory activity was
      assessed by paw plethysmometry in adult rats using the carrageenin-induced paw
      edema test. Subcutaneous administration of MPCA (22, 66, and 200 mg/kg) induced a
      dose-dependent decrease in the time spent licking during the neurogenic and
      inflammatory phases of the formalin test, and preadministration of naloxone (1
      mg/kg, sc) did not prevent MPCA-induced (200 mg/kg, sc) antinociception. Naloxone
      decreased the spontaneous locomotor activity of mice, while MPCA had no effect on
      locomotion. In contrast, administration of the opioid antagonist caused a
      significant increase in the locomotor behavior of mice previously injected with
      MPCA. MPCA was devoid of antinociceptive action by the tail-immersion test and of
      anti-inflammatory activity. Moreover, MPCA had no effect on the motor performance
      of mice in the rotarod test. These results suggest that MPCA induces
      antinociception in the neurogenic and inflammatory phases of the formalin test,
      an effect that does not involve opioid receptors.

PMID- 11325409
TI  - Estrus variation in anticonflict effects of midazolam microinjected into septal
      nuclei in female Wistar rats.
AB  - Effects of midazolam intraperitoneally (3.0 mg/kg) administered, or locally
      applied into lateral septal nuclei (10 microg/microl), or into the medial septum
      (10 microg/microl) were assessed in Wistar rats during late proestrus or
      metestrus-diestrus in a conflict-operant task. A reduction in conflict behavior
      was found in control rats during late proestrus (P<.05), when compared to
      metestrus-diestrus. Systemic injections of midazolam (P<.05) or midazolam
      infusions into lateral septal nuclei (P<.05) also reduced conflict behavior only
      during late proestrus, whereas midazolam infusions into the medial septum
      produced neither of these anticonflict effects in any estrous phase. In
      conclusion, an endocrine-related variation in anticonflict effects of midazolam
      microinjected into lateral septal nuclei was displayed by female rats.

PMID- 11325410
TI  - Delta(9)-THC stimulates food intake in Lewis rats: effects on chow, high-fat and
      sweet high-fat diets.
AB  - Free-feeding adult male Lewis rats were administered intraperitoneal (i.p.)
      Delta(9)-tetrahydrocannabinol (THC) in doses of 0.5, 1.0 and 2.5 mg/kg, and
      effects on food intake were measured at 1, 2, 4, 6 and 24 h postinjection. Rats
      were fed rat chow, a high-fat diet (HF) or a high-fat sweetened (HFS) diet. Small
      increases in HF and HFS intake following doses of 0.5 or 1.0 mg/kg were seen at
      1, 2 and 4 h, but not 6 or 24 h compared to vehicle intake. Increases following
      0.5 and 1.0 mg/kg did not differ from each other at any time point and 2.5 mg/kg
      produced smaller differences at all time points. There was no difference between
      HF or HFS intake at any time point although larger increases were seen in the HF
      group compared to both chow and HFS following 0.5 and 1.0 mg/kg. This work
      confirms previous data in both humans and rats indicating a stimulatory role for
      cannabinoids in ingestive behavior.

PMID- 11325411
TI  - Subchronic cocaine produces training paradigm-dependent learning deficits in
      laboratory rats.
AB  - The effect of cocaine on spatial learning was investigated by exposing male
      Sprague-Dawley rats to 0, 20, or 40 mg/kg cocaine prior to and during training on
      a water maze task. Half the animals were pretrained on cued trials prior to
      hidden platform trials, while the remaining animals completed hidden platform
      trials immediately. Escape latencies for all animals improved with training, but
      pretrained animals located the hidden platform faster than untrained animals
      (P<.001). Pretraining also decreased the effect of cocaine. In pretrained
      animals, only the high dose of cocaine caused significant increases in escape
      latency (P<.001), while in the untrained group the lower dose of cocaine also
      caused a significant increase (P<.001). On working memory measures, cocaine
      affected both the pretrained (P<.01) and untrained (P<.001) groups. Dwell ratio
      measurements indicated unaffected reference memory in both pretrained (P<.001)
      and untrained (P<.001) animals, and no significant differences were detected
      among the treatment conditions in either group (P>.05). Thus, while cocaine did
      not abolish learning, the efficiency with which the task was learned was
      compromised. However, this effect was reduced by pretraining.

PMID- 11325412
TI  - NaCl preference increases during pregnancy and lactation: assessment using brief
      access tests.
AB  - Pregnancy and lactation are characterized by increases in NaCl intake, as
      determined by long-term consumption tests, which cannot examine the relative
      contribution of taste and postingestive factors to this phenomenon. Consequently,
      in this study, changes in NaCl preference during pregnancy and lactation were
      studied in nulliparous Long-Evans rats using a brief access test (lickometer). In
      Experiment 1, rats were maintained on a Na(+)-adequate diet (0.03% Na(+)),
      habituated to lickometer testing, and subsequently assessed during pregnancy and
      lactation with three 30-s exposures to each of seven taste solutions: 0.075 M
      sucrose (base), 0.089 M NaCl in base, 0.158 M NaCl in base, 0.281 M NaCl in base,
      0.5 M NaCl in base, 0.158 M NaCl and 0.281 M NaCl. Results indicated higher lick
      rates to the 0.5 M NaCl in base, 0.158 M NaCl and 0.281 M NaCl solutions during
      late pregnancy and late lactation (Day 13 and beyond). In Experiment 2, a
      comparison of two diets differing in sodium content (0.03% vs. 0.3% Na(+))
      determined that these changes in NaCl preference during pregnancy and lactation
      were unrelated to dietary sodium. Thus, the apparent increase in NaCl preference
      during pregnancy and lactation, independent of dietary sodium, suggests that this
      change in preference is not in response to physiological sodium need.

PMID- 11325413
TI  - The effect of (R)-HA966 or ACEA 1021 on dexfenfluramine or (S)-MDMA-induced
      changes in temperature, activity, and neurotoxicity.
AB  - The glycine site-specific N-methyl-D-aspartate (NMDA) antagonist 5-nitro-6,7
      dichloro-2,3-quinoxalinedione (ACEA 1021, 4x30 mg/kg, i.p.) given 30 min before
      dexfenfluramine (4x15 mg/kg, i.p., every 2 h) was unable to prevent
      dexfenfluramine-induced depletion of 5-hydroxytryptamine (5-HT), 5
      hydroxyindoleacetic acid (5-HIAA) content, and 5-HT transporter (5-HTT) density.
      Another glycine site-specific NMDA antagonist, R(+)-3-aminohydroxypyrrolidin-2
      one [(R)-HA 966] (2x30 mg/kg, ip), given 30 min before dexfenfluramine (2x10
      mg/kg, ip, 2 hourly) was also unable to prevent regional depletion of 5-HT, 5
      HIAA, and 5-HTT density. However, ACEA 1021 (4x30 mg/kg, i.p.) given 30 min
      before (S)-3,4-methylenedioxymethamphetamine (MDMA, 4x10 mg/kg, 2 hourly, ip)
      attenuated the regional depletion of dopamine (DA), dihydroxyphenylacetic acid
      (DOPAC), 5-HT, 5-HIAA content, and 5-HTT density. ACEA 1021 combined with (S)
      MDMA also prevented (S)-MDMA-induced hyperthermia without causing hypothermia or
      preventing an (S)-MDMA-induced increase in locomotor activity.

PMID- 11325414
TI  - Reproductive experience modulates dopamine-related behavioral responses.
AB  - Reproductive experience (RE), i.e., mating, pregnancy, parturition and lactation,
      has long-term physiological effects. It reduces the basal levels of circulating
      prolactin in parous women, decreases the intensity of nocturnal and diurnal
      prolactin surges in multigravid rats during early pregnancy, as well as the
      hormonal and neurochemical responses to the dopamine receptor antagonists
      metoclopramide and haloperidol. In the present study, we evaluated the possible
      influences of RE on some dopaminergic-related behaviors: (1) acute responses to a
      new environment represented by an open-field arena plus injection stress; (2)
      modulation of behavior after a short-term withdrawal subsequent to 7 days
      amphetamine (AMPH) pretreatment; (3) stereotypy elicited by AMPH and apomorphine
      (APO); and (4) APO-induced hypothermia. In the 3-min open-field test, there was a
      decrease in locomotor activity as a function of RE. Behavioral depression was
      mild and AMPH pretreatment revealed RE alterations. APO-induced stereotyped
      behavior was slightly more intense in primiparous animals, although no
      significant differences were found in AMPH-induced stereotyped behavior. No
      differences were observed between intact and ovariectomized primiparous and
      nulliparous animals in APO-induced hypothermia. Our data suggest that RE modifies
      some DA-related behavioral responses. The physiological relevance of the
      phenomenon is discussed.

PMID- 11325415
TI  - Pimozide, like extinction, devalues stimuli associated with sucrose taking.
AB  - Conditioned stimuli (CS) can be devalued by exposure to those stimuli in the
      absence of primary reward. We tested the hypothesis that dopamine (DA) mediates
      the control of behavior by conditioned appetitive stimuli. Long-Evans rats were
      trained to respond for sucrose under a heterogeneous chain schedule in which
      seeking responses (lever press) turned on a houselight [variable interval (VI)
      120 s]; taking responses (wheel turn or chain pull) in the presence of the
      houselight were reinforced [fixed ratio (FR)-1] by a sucrose pellet. When
      responding on this schedule was stable, the levers were retracted and subjects
      had access to the sucrose-taking manipulandum only. Sucrose-taking responses were
      either extinguished or reinforced under the influence of the DA antagonist,
      pimozide. Control groups were also reinforced for sucrose-taking responses but
      received no injection or a vehicle injection prior to each session. Responses of
      extinction and pimozide-treated groups declined over sessions. Sucrose-seeking
      responses were measured in a later test when subjects had no access to the
      sucrose-taking manipulandum or to the reinforcer. Both extinction and pimozide
      manipulations reduced seeking responses, relative to the respective control
      groups. Pimozide injections in the home cage had no effect. These data support
      the idea that DA mediates the conditioned reinforcing properties provided by
      access to the taking link of the chain.

PMID- 11325416
TI  - Sex differences in sensitivity to seizures elicited by pentylenetetrazol in mice.
AB  - Sex differences in sensitivity to seizures elicited by intraperitoneally injected
      pentylenetetrazol (PTZ) were studied in 240 (120 males and 120 females) adult
      Swiss mice. Animals were separated into four groups according to the dose that
      was injected: 40, 50, 60 and 70 mg/kg. Seizure severity was expressed by the
      following scoring scale: (0) no abnormal behavior; (1) myoclonus; (2) running
      bouncing (RB) clonus; (3) tonic hind limb extension (THE). The analyses of the
      dose-response curves indicated that females were more susceptible than males when
      the 50- and 60-mg/kg doses were used. Specifically, females often displayed RB
      clonus, while males frequently displayed only myoclonus or no abnormal behavior.
      No significant sex differences were demonstrated when either the 40- or the 70
      mg/kg doses were used. These data indicate that, for a specific range of doses,
      sex differences in seizure susceptibility can be clearly demonstrated with the
      use of intraperitoneally injected PTZ. In this sense, this method could be used
      as a tool to investigate the role played by sexual hormones in regulating the
      sensitivity of the gamma-aminobutiric acid (GABA(A)) receptor complex (GRC).

PMID- 11325417
TI  - Depletion of brown fat norepinephrine content by acute cold exposure and
      adrenoceptor blockade.
AB  - Experiments were conducted to characterize the effects of acute cold exposure,
      with and without adrenoceptor blockade, on intrascapular brown adipose tissue
      (IBAT) and adrenal catecholamine content in male Sprague-Dawley rats. Groups of
      animals with indwelling temperature transmitters were tested following treatment
      with saline, the alpha-adrenoceptor blocker phentolamine, the beta-adrenoceptor
      blocker propranolol, combined blockade with phentolamine plus propranolol, and
      the ganglionic blocker chlorisondamine. IBAT norepinephrine (NE) content was not
      affected in animals tested at 22 degrees C, but was reduced in 4 degrees C
      exposed animals treated with phentolamine (-57%), phentolamine plus propranolol (
      97%), and chlorisondamine (-42%). Adrenal NE and epinephrine (EPI) content were
      not altered by the treatments at 4 degrees C or 22 degrees C. None of the
      treatments affected the temperature of animals at 22 degrees C, but significant
      hypothermia occurred at 4 degrees C after chlorisondamine (-2.3+/-0.3 degrees C)
      and the combination of phentolamine and propranolol (-1.5+/-0.4 degrees C). These
      results suggest that cold exposure alone did not affect IBAT NE content, but when
      cold exposure was combined with adrenoceptor blockade, the sympathetic activation
      was sufficient to cause a reduction in IBAT NE content. In addition, alpha- and
      beta-adrenoceptor-mediated mechanisms contribute to the maintenance of core
      temperature. However, both alpha- and beta-receptor mechanisms had to be
      interrupted before a deficit in body temperature was detected.

PMID- 11325418
TI  - Morphine-induced conditioned taste aversions in the LEW/N and F344/N rat strains.
AB  - Previous reports have shown that the LEW/N and F344/N inbred rat strains display
      a differential sensitivity to cocaine in a number of preparations, with the LEW/N
      rats displaying an increased sensitivity to both the reinforcing and aversive
      effects of cocaine (relative to the F344/N rats). Given that the LEW/N rats are
      also more sensitive to the reinforcing effects of morphine than the F344/N
      strain, the present experiment examined the ability of morphine to condition
      taste aversions in the LEW/N and F344/N strains to determine if the general
      sensitivity to cocaine generalizes to another drug of abuse. Specifically, on
      four conditioning trials, 35 LEW/N and 33 F344/N female rats were allowed access
      to a novel saccharin solution and then injected with varying doses of morphine
      (0, 10, 32 and 56 mg/kg). On intervening recovery days, subjects were allowed 20
      min access to water. Following the fourth trial, a final aversion test was
      administered. The F344/N rats, but not the LEW/N rats, rapidly acquired morphine
      induced taste aversions at all doses of morphine. Pharmacokinetic differences
      between the strains were also assessed. Specifically, 10 mg/kg morphine (or
      vehicle) was administered to subjects of both strains and plasma morphine levels
      were analyzed at 0.5, 2 and 4 h postinjection. No differences in plasma levels
      between the strains were observed. Unlike with cocaine, the LEW/N rats do not
      seem generally sensitive to morphine (relative to the F344/N rats). Rather, the
      differential sensitivity of the two strains to these compounds seems to be
      preparation dependent. Possible mechanisms underlying the differential
      sensitivity evident in the strains were discussed.

PMID- 11325419
TI  - Assessing the abuse potential of methylphenidate in nonhuman and human subjects:
      a review.
AB  - Methylphenidate (MPH) is widely used for the treatment of Attention Deficit
      Hyperactivity Disorder (ADHD) in children, adolescents, and adults.
      Methylphenidate is clearly effective for the treatment of ADHD, but there is
      controversy as to whether it has significant abuse potential like other
      psychostimulants (e.g., D-amphetamine and cocaine). In general, the drug is
      believed to be abused at rates much lower than those for other stimulants. The
      present review examines studies that investigated the behavioral pharmacological
      profile of methylphenidate and discusses how results from these studies address
      its abuse liability. Using MEDLINE search terms methylphenidate, drug
      discrimination, reinforcement, self-administration, subjective effects, subject
      rated effects, abuse potential, and abuse liability, along with a review of the
      references from identified articles, 60 studies were located in which the
      reinforcing, discriminative-stimulus, or subjective effects of methylphenidate
      were directly assessed in nonhumans or humans. Forty-eight (80.0%) of the studies
      reviewed indicate that methylphenidate either functions in a manner similar to D
      amphetamine or cocaine (e.g., functions as a reinforcer, substitutes fully in
      drug discrimination experiments), or produces a pattern of subjective effects
      suggestive of abuse potential. The results are discussed as they pertain to
      factors that may account for the apparent discrepancy in abuse rates between
      methylphenidate and other stimulants, including characterization of actual abuse
      rates, defining abuse and misuse, pharmacokinetic factors, and validity of abuse
      liability assays.

PMID- 11325420
TI  - Effects of water activity and aqueous solvent ordering on thermal stability of
      lysozyme, alpha-chymotrypsinogen A, and alcohol dehydrogenase.
AB  - Effects of water activity (aW) and solvent ordering were separately analyzed on
      the thermal unfolding of lysozyme and alpha-chymotrypsinogen A, and also on the
      thermal deactivation of yeast alcohol dehydrogenase (YADH) in aqueous solutions
      with various additives. With the coexistence of additives, water activity was the
      determinant of the extent of the change in the thermal stability of proteins
      while solvent ordering was the determinant of the direction of the change. The
      parameter alpha, determined from the activity coefficient of water, representing
      the deviation of aW from that of the ideal solution, was useful as a quantitative
      index of the solvent ordering showing good correlations with the unfolding
      temperature and enthalpy of lysozyme and alpha-chymotrypsinogen A and also with
      the thermal deactivation rate constant of YADH at a constant aW. Solvent ordering
      seemed to affect the thermal stability of proteins mainly through its effect on
      the intramolecular hydrophobic interaction among amino acid residues in a protein
      molecule but the contribution of the electrostatic interaction including hydrogen
      bonding through the change in permittivity of solution was also suggested.

PMID- 11325421
TI  - Low-degree oxidized scleroglucan and its hydrogel.
AB  - A controlled oxidation of scleroglucan was performed with sodium periodate to
      prepare aldehyde derivatives (scleraldehyde) with a low degree of oxidation (10
      and 20%), which were utilized for crosslinking reactions with
      hexamethylenediamine. The structural characterization of scleraldehydes and their
      corresponding hydrogels was attempted by small-angle X-ray scattering (SAXS).
      While scleraldehyde with a higher degree of oxidation (> or = 50%), according to
      an earlier research, was found to disentangle into single chains as the degree of
      oxidation increases; scleroglucan bearing a low percentage of aldehydic groups
      (up to 20%) retains mainly the conformation of the natural polysaccharide, thus
      the system can be represented as composed of triple helices with only minor
      disentanglements at the sites where the aldehyde groups are present. The hydrogel
      prepared from scleraldehyde with a low degree of oxidation is brittle and
      fragmented, in contrast to the elastic/homogeneous hydrogel earlier prepared from
      scleraldehyde with a high degree of oxidation. The hydrogel from scleraldehyde
      with a low degree of oxidation was found to possess a network structure that
      consisted mostly of the triple helices crosslinked in specific points where the
      triple helices are disentangled into single chains because of the presence of the
      aldehyde groups.

PMID- 11325422
TI  - Determination of the degree of acetylation of chitin materials by 13C CP/MAS NMR
      spectroscopy.
AB  - 13C CP/MAS NMR spectroscopy has been shown to be a powerful tool to quantify the
      degree of acetylation of chitin and chitosan. In order to optimise the parameters
      which afford quantitative 13C cross-polarisation magic-angle spinning NMR
      spectra, a detailed relaxation study has been carried out on selected chitin and
      deacetylated chitin samples. A relaxation delay of 5 s and a contact time of 1 ms
      have been found to yield quantitative NMR spectra of samples with deacetylation
      degree values of 0.68 and 0.16. The measured spin-lattice relaxation times in the
      rotating frame, T(1rhoH), are in the range 6.4-8.9 ms for chitin and 4.3-7.3 ms
      for deacetylated chitin, while TCH values for both samples are very similar and
      range from 0.03 to 0.19 ms. Spin-counting experiments indicate that, within
      experimental error, all carbon is detected by NMR indicating that the samples
      studied contain no (or very few) paramagnetic centres.

PMID- 11325423
TI  - Peanut (Arachis hypogaea) lectin recognizes alpha-linked galactose, but not N
      acetyl lactosamine in N-linked oligosaccharide terminals.
AB  - Peanut (Arachis hypogaea) agglutinin (PNA) is extensively used as tumour marker
      as it strongly recognises the cancer specific T antigen (Galbeta1-->3GalNAc-),
      but not its sialylated version. However, an additional specificity towards
      Galbeta1-->4GlcNAc (LacNAc), which is not tumour specific, had been attributed to
      PNA. For correct interpretation of lectin histochemical results we examined PNA
      sugar specificity using naturally occurring or semi-synthetic glycoproteins,
      matrix-immobilised galactosides and lectin-binding tissue glycoproteins, rather
      than mono- or disaccharides as ligands. Dot-blots, transfer blots or polystyrene
      plate coatings of the soluble glycoconjugates were probed with horse-radish
      peroxidase (HRP) conjugates of PNA and other lectins of known specificity.
      Modifications of PNA-binding glycoproteins, including selective removal of O
      linked oligosaccharides and treatment with glycosidases revealed that Galbeta1-
      >4GlcNAc (LacNAc) was ineffective while terminal alpha-linked galactose (TAG) as
      well as exposed T antigen (Galbeta1-->3 GalNAc-) was excellent as sugar moiety in
      glycoproteins for their recognition by PNA. When immobilised, melibiose was
      superior to lactose in PNA binding. Results were confirmed using TAG-specific
      human serum anti-alpha-galactoside antibody.

PMID- 11325424
TI  - The specific hydrolysis of HIV-1 TAR RNA element with the anti-TAR hammerhead
      ribozyme: structural and functional implications.
AB  - The main transcriptional regulator of the human immunodeficiency virus is the Tat
      protein, which recognises and binds to a fragment RNA at the 5' end of viral
      mRNA, named transactivation response element (TAR) RNA. Extensive mutagenesis
      studies have shown that a region of TAR RNA important for Tat binding involves a
      set of nucleotides surrounding a characteristic UCU nucleotide bulge. The
      specific Tat-TAR complex formation enhances the rate of transcription elongation
      but inhibition of that interaction prevents the human immunodeficiency virus type
      1 (HIV-1) replication. If so, a possibility of virus inactivation would be a site
      specific degradation of the TAR RNA element. To break down and inactivate TAR
      RNA, we designated the anti-hammerhead (HH) ribozyme to cleave nucleosides within
      the bulge. We showed for the first time the new type of the AUC hammerhead
      ribozyme, which hydrolyses specifically the TAR RNA element at C8 nucleotide in
      the bulge (C24 in the standard TAR RNA numbering). The cleavage reaction has
      broad magnesium requirements. Mn and particularly Ca are less efficient.
      Argininamide interferes with the cleavage of TAR RNA induced by the ribozyme.
      These results have two implications; (i) structural, where the HIV-1 TAR RNA
      element in solution occurs in equilibrium of only two forms, one of which, a
      double stranded RNA, meets structural requirements for ribozyme pairing and
      cleavage, and (ii) functional, the HH ribozyme can be explored for an
      inactivation of HIV-1 through the TAR RNA element deintegration.

PMID- 11325425
TI  - Preparation of gellan sulfate as an artificial ligand for removal of extra domain
      A containing fibronectin.
AB  - The extra domain A containing fibronectin (EDA(+)FN) concentration in plasma of
      rheumatoid arthritis (RA) is abnormally higher than the normal level. We
      synthesized various gellan-sulfate (GS) candidates as artificial ligands for
      removing EDA(+)FN from plasma. The interaction between these artificial ligands
      and EDA(+)FN was evaluated using affinity constants (KA), which were determined
      by surface plasmon resonance measurement. The KA (3.6 x 10(8) per M) of GS-25
      [degree of substitution for sulfonation (DS) = 25%] with EDA(+)FN was higher than
      those of other molecules: GS-16 (DS=16%) at 8.3 x 10(7) per M, and GS-35 (DS =
      35%) at 1.7 x 10(8) per M. Furthermore, GSs displayed selectivity of EDA(+)FN for
      binding with plasma FN (KAEDA(+)FN)/KA(plasma FN)>2). The removal ratio in plasma
      was measured by using GS-immobilized gel. Removals of 66, 11, 7.7, 6.2, 6.9, and
      12% for EDA(+)FN, plasma FN, fibrinogen, albumin, immunoglobulin G (IgG) and
      antithrombin III from the patient-model plasma were, respectively, achieved with
      GS-25-immobilized gel. These results suggest that GS may be used as a selective
      artificial ligand for EDA(+)FN removal from plasma in RA treatment.

PMID- 11325426
TI  - Physico-chemical studies on DNA triplexes containing an alternate third strand
      with a non-nucleotide linker.
AB  - Differential scanning calorimetric (DSC), circular dichroism (CD) and molecular
      mechanics studies have been performed on two triple helices of DNA. The target
      duplex consists of 16 base pairs in alternate sequence of the type 5'
      (purine)m(pyrimidine)m-3'. In both the triplexes, the third oligopyrimidine
      strand crosses the major groove at the purine-pyrimidine junction, with a
      simultaneous binding of the adjacent purine tracts on alternate strands of the
      Watson-Crick duplex. The switch is ensured by a non-nucleotide linker, the 1,2,3
      propanetriol residue, that joins two 3'-3' phosphodiester ends. The third strands
      differ from each other for a nucleotide in the junction region. The resulting
      triple helices were termed 14-mer-PXP and 15-mer-PXP (where P = phosphate and X =
      1,2,3-propanetriol residue) according to the number of nucleotides that compose
      the third strand. DSC data show two independent processes: the first
      corresponding to the dissociation of the third strand from the target duplex, the
      second to the dissociation of the double helix in two single strands. The two
      triple helices show the same stability at pH 6.6. At pH 6.0, the 15-mer-PXP
      triplex is thermodynamically more stable than the 14-mer-PXP triplex.
      Thermodynamic data are discussed in relation to structural models. The results
      are useful when considering the design of oligonucleotides that can bind in an
      antigene approach to the DNA for therapeutic purposes.

PMID- 11325427
TI  - Anticoagulant properties of a sulfated galactan preparation from a marine green
      alga, Codium cylindricum.
AB  - An anticoagulant was isolated from a marine green alga, Codium cylindricum. The
      anticoagulant was composed mainly of galactose with a small amount of glucose,
      and was highly sulfated (13.1% as SO3Na). The anticoagulant properties of the
      purified anticoagulant were compared with that of heparin by assays of activated
      partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT)
      using normal human plasma. The anticoagulant showed similar activities with
      heparin, however, weaker than heparin. On the other hand, the anticoagulant did
      not affect PT even at the concentration at which APTT and TT were strongly
      prolonged. The anticoagulant did not potentiate antithrombin III (AT III) and
      heparin cofactor II (HC II), thus the anticoagulant mechanism would be different
      from that of other anticoagulants isolated so far from the genus Codium.

PMID- 11325428
TI  - Competitive sorption of platinum and palladium on chitosan derivatives.
AB  - Glutaraldehyde-cross-linked chitosan (GCC), thiourea derivative of chitosan (TGC)
      and rubeanic acid derivative of chitosan (RADC) have previously been shown to be
      very efficient at removing platinum and palladium from single component dilute
      acidic solutions. This study examines the competitive sorption of these metal
      anions in bi-component mixtures for GCC, TGC and RADC. Palladium sorption is less
      sensitive to the presence of platinum than the reverse: the maximum sorption
      capacity decreases less for palladium than for platinum in the presence of the
      competitor anion (the metals being in their chloro-metal forms). Moreover, the
      Langmuir-shape of the sorption isotherm for palladium is unaffected (with the
      usual plateau reached at low residual palladium), while in the case of platinum
      sorption, the isotherms exhibit a significant decrease of the sorption capacity
      at high residual platinum concentration which increases with increasing
      concentrations of palladium. RADC is more selective for palladium over platinum
      than the other chitosan derivatives. A preliminary study of the competitive
      sorption kinetics in both batch and fixed bed systems is presented for RADC and
      confirms the higher affinity of the sorbent for palladium than for platinum.

PMID- 11325429
TI  - Amylopectin aggregation as a function of starch phosphate content studied by size
      exclusion chromatography and on-line refractive index and light scattering.
AB  - Starches with a natural 65-fold span in covalently bound phosphate content were
      prepared from five different crops including sorghum, cassava, three potato
      varieties and an exotic ginger plant, Curcuma zedoaria, with extreme starch
      phosphate content. These starches were subjected to size exclusion chromatography
      with refractive index detection (SEC/RI). A simple and rapid method for starch
      solubilisation was used. The conditions during solubilisation (2 M NaOH) and
      separation (10 mM NaOH, 50 degrees C) were such as enabling > 94% recovery of the
      starch without detectable degradation. The aggregation properties of the starch
      was investigated using on line refractive index/multi angle laser light
      scattering (RI/MALLS) detection. Three major regions in the SEC profile were
      identified, consisting of large amylopectin aggregates, amylopectin particles
      with radius of gyration (Rg) of approx 200 nm (400 nm blocklets) and amylose. A
      procedure for correction of light scattering signals spread over the SEC profile
      as a result of aggregate tailing was developed. The significance of the relative
      amounts of these three molecular species on standard starch pasting parameters,
      as measured by a Rapid Visco Analyzer (RVA), was investigated. Starches with a
      high amount of amylopectin aggregates showed high peak viscosities. Moreover,
      very high amounts of starch bound phosphate or amylose appears to suppress the
      content of large aggregates resulting in low viscosity.

PMID- 11325430
TI  - The use of in vivo direct drug application to assess neural regulation of muscle
      properties.
AB  - Skeletal muscle is a convenient model system for studying basic questions on the
      neural regulation of synaptogenesis and of many properties of sarcolemma and
      contractile apparatus. The study of the neural signals involved in a particular
      regulation and of the mediating intracellular pathways, requires the chronic
      application of drugs, second messengers, antibodies, trophic factors and the
      like. The most common way of application is in vitro treatment of muscle cell
      lines or primary myotube cultures. As an alternative to tissue culture, we
      developed a technique for in vivo application of the agents under study directly
      on skeletal muscle. An initial surgical step secures the tip of a fine
      polyethylene catheter (<or=250 microm) onto the proximal surface of the adult rat
      soleus muscle. The onset of perfusion of the solution containing the agent,
      however, starts only 10-15 days later, pushed by an implanted Alzet pump
      connected to the catheter. After chronic in vivo treatment for the appropriate
      number of days, the muscle is processed as needed. We used various agents which
      are known to affect muscle fibre acetylcholine receptor regulation, namely, CGRP,
      tetrodotoxin, and KCl and obtained results which demonstrate the full
      effectiveness of this way of application.

PMID- 11325431
TI  - A simple method to microinject solid neural tracers into deep structures of the
      brain.
AB  - We have developed an instrument to perform microinjections of solid neural
      tracers into deep structures of the brain. The instrument consists of a thin
      hypodermic needle equipped with a movable internal rod, which is connected to a
      pressure chamber. When a pressure pulse is applied to the chamber, the rod moves
      forward and back inside the needle, pushing out a solid load previously packed
      inside the needle tip. By attaching a microelectrode to the instrument, it is
      also possible to have electrophysiological control of the injection placement. To
      test the instrument, we microinjected DiI and rhodamine crystals into selected
      structures of the visual system of pigeons. The results show small, well-defined
      injection sites, accurately located in the desired targets, together with well
      developed anterogade and retrograde transport, selectively originated from the
      injection sites. This method extends the usage of solid tracers to most
      structures in the brain and may, in certain cases, be more advantageous than the
      conventional method of injecting tracer solutions.

PMID- 11325432
TI  - Immunohistochemistry in association with scanning electron microscopy for the
      morphological characterization and location of astrocytes of the rabbit retina.
AB  - The purpose of the present investigation was to establish a method for the
      morphological characterization and location of the several types of astrocytes in
      the rabbit retina. Whole retinas were incubated with unlabeled antibody to glial
      fibrillary acidic protein (GFAP) and, afterwards, treated with secondary antibody
      labeled according to the requirements for the visualization of the antigen
      antibody reaction either with the confocal or transmission electron microscope.
      Specimens treated similarly to the latter were osmium enhanced and analyzed with
      scanning electron microscopy (SEM). The different immunohistochemical approaches
      led to the conclusion that the cells selectively visualized with the SEM are
      astrocytes. The higher resolution and depth of focus of this instrument allowed a
      better morphological characterization and a more precise location of the
      astrocytes in the several levels of the inner portion of the rabbit retina. The
      method described herein, in which pre-embedding immunohistochemistry for GFAP on
      rabbit retinas was associated with osmium enhancement and examination with SEM,
      proved to be reliable and efficient for the morphological characterization and
      location of astrocytes.

PMID- 11325433
TI  - A novel method for detecting licking behavior during recording of
      electrophysiological signals from the brain.
AB  - We have developed a novel method for detecting licking at a fluid well that is
      compatible with behavioral neurophysiology. This method uses off-the-shelf fiber
      optic technology to introduce a light beam through the fluid-air interface of a
      fluid bolus in a well. A self-adjusting optical sensor detects licking as
      disturbances in the amplified light surface within the interface when the fluid
      is disturbed. The proper configuration of fluid well and fiber optics will
      reliably detect licking and introduce no artifacts into simultaneous high
      impedance recordings of extracellular neural activity. This method is also
      compatible with delivery of multiple fluids to the same well. Unlike present
      methods of detecting licking in neurophysiological experiments, our approach does
      not involve the passage of current or capacitance changes in which the animal
      forms part of a circuit, nor does it require movement of the licking apparatus or
      any other response beyond the actual licking of the fluid. As a result, noise
      artifacts in the unit recordings do not occur, and the sensor is highly resistant
      to artifacts caused by exploration or licking at the fluid well in the absence of
      liquid. We present neural recording data from units in the nucleus accumbens
      demonstrating these properties of the lick detector.

PMID- 11325434
TI  - A simple cuff electrode for nerve recording and stimulation in acute experiments
      on small animals.
AB  - We describe a cuff-type electrode specifically designed for recording from, and
      electrical stimulation of, cut nerves in acute experiments on small animals.
      Unlike existing designs of cuff electrodes, it is simple to manufacture,
      inexpensive and takes little time to implant. The electrode was tested on the
      hypoglossal, phrenic, recurrent laryngeal, and superior laryngeal nerves in
      anesthetized rats. It provides satisfactory signal-to-noise ratios (3.0+/-0.8
      (mean+/-S.D.)) for hypoglossal and 5.4+/-2.1 for phrenic nerve activity and
      stable recording over the time course of a typical acute experiment. It
      eliminates or minimizes the problems with recording stability and space
      availability associated with conventional hook-type electrodes, and reduces
      experiment preparation time. This should facilitate neurophysiological
      experiments on small rodents involving complex protocols that include recording
      from, and/or stimulation of, multiple nerves.

PMID- 11325435
TI  - Serum-free culture of dissociated, purified adult and aged sympathetic neurons
      and quantitative assays of growth and survival.
AB  - In vitro studies of dissociated neurons have provided crucial data regarding the
      regulation of plasticity in embryonic and perinatal neurons from both central and
      peripheral nervous systems. There have been few attempts to apply these methods
      to adult or aged neurons and the methods that have been reported have not been
      able to dissect the possible confounding contributions of non-neuronal cells and
      serum. Furthermore, quantitative assays of cultured neurons, particularly of
      their growth, have rarely been described. We report here the development of a
      novel method for the dissociation, purification and culture of sympathetic
      neurons from the adult and aged rat SCG under serum free conditions and in
      defined media. The technique results in a relatively high yield of viable,
      growing neurons. We describe methods for assaying the total yield of neurons, the
      proportion of surviving neurons and the proportion of neurons initiating neurite
      outgrowth after plating. A novel semiautomated assay of neurite outgrowth is
      outlined using image analysis of composite images of immunofluorescence-stained
      single neurons.

PMID- 11325436
TI  - An apparatus and behavioral training protocol to conduct positron emission
      tomography (PET) neuroimaging in conscious rhesus monkeys.
AB  - Nonhuman primates offer a unique resource in neuroimaging research, providing the
      opportunity to manipulate appropriate biological and behavioral variables under
      well-controlled experimental conditions in an animal model that is closely
      related to humans, both functionally and neuroanatomically. The present report
      describes the development and standardization of PET neuroimaging protocols in
      conscious rhesus monkeys and their application to characterize the acute effects
      of cocaine on cerebral blood flow. Specific attention was devoted to the
      development of an effective and comfortable head restraint device to be used in
      the imaging of conscious monkeys. The restraint device was designed to attach to
      a standard primate chair to facilitate frequent immobilization. Subjects received
      extensive behavioral training prior to neuroimaging in order to ensure their
      comfort and minimize potential stress associated with the imaging protocols.
      Functional changes in cerebral blood flow were characterized in three subjects
      with the positron-emitting tracer 15O water following acute i.v. administration
      of cocaine. Regions of interest were defined on MRI scans with a high degree of
      accuracy. Cocaine caused pronounced increases in cerebral blood flow at 5 min
      postinjection that diminished markedly within 25 min. The results document the
      feasibility to conduct PET neuroimaging studies of cerebral blood flow in
      conscious nonhuman primates. Extension of the methodology to include brain
      activation during behavioral studies could contribute significantly to the
      growing discipline of behavioral neuroscience.

PMID- 11325437
TI  - Kalman filter detection of blinks in video-oculography: applications for VVOR
      measurement during locomotion.
AB  - A Kalman filter algorithm was implemented for automatic detection of blink
      artifacts in video-oculography (VOG) data, and a cubic spline used to patch the
      eliminated data. The algorithm was tested by randomly introducing artificial
      blinks into eye movement data and computing the errors introduced by the patches.
      We also computed visual vestibulo-ocular reflex (VVOR) gain and phase in healthy
      and vestibulopathic subjects during a locomotor task, before and after blink
      removal, to demonstrate the interpretive importance of eliminating blink
      artifacts. The error introduced by the patched data was small (0.50+/-0.32
      degrees ) and within the resolution of head angle measurements. Comparison of
      gain and phase shift before and after removing blinks revealed that even when
      calculated values are within expected limits, coherence of the VVOR signal was
      significantly (p=0.003) lower prior to blink removal (0.51+/-0.37) compared to
      that after blink removal (0.92+/-0.08). Comparison of VVOR calculations between
      healthy and vestibulopathic subjects (after removal of blinks) revealed that
      vestibulopathic subjects had significantly decreased gains (p=0.018) and
      increased phase shifts (p=0.009): these results agree with data reported in
      literature. We conclude that the Kalman filter detection and cubic spline
      patching algorithms are useful tools for VOG and should enable reliable VVOR
      measurements during unconstrained, ecologically meaningful locomotor activities.

PMID- 11325438
TI  - Single-cell recording from the brain of freely moving monkeys.
AB  - Single-cell recording from the brain of non-human primates has traditionally been
      performed in monkeys seated in a primate chair. However, this arrangement makes
      long-term recordings difficult, causes stress that may confound the data, and
      prevents the manifestation of natural behaviors. Extending our previous
      neurophysiological studies in non-human primates (Ludvig et al. Brain Res.
      Protocols 2000;5:75-85), we have developed a method for recording the electrical
      activity of single hippocampal neurons in freely moving squirrel monkeys (Saimiri
      sciureus). The recording sessions lasted for up to 6 h, during which the monkeys
      moved freely around on the walls and the floor of a large test chamber and
      collected food pellets. Stable action potential waveforms were readily kept
      throughout the sessions. The following factors proved to be critical in this
      study: (a) selecting squirrel monkeys for the experiments, (b) using a driveable
      bundle of microwires for the recordings, (c) using a special recording cable, (d)
      implanting the microwires into the brain without causing neurological deficits,
      and (e) running the recording sessions in a special test chamber. The described
      method allows long-term extracellular recordings from the brain of non-human
      primates, without the stress of chairing, during a wide range of natural
      behaviors. Using this model, new insights can be obtained into the unique firing
      repertoire of the neurons of the primate brain.

PMID- 11325439
TI  - Genomic instability: potential contributions to tumour and normal tissue
      response, and second tumours, after radiotherapy.
AB  - PURPOSE: Induced genomic instability generally refers to a type of damage which
      is transmissible down cell generations, and which results in a persistently
      enhanced frequency of de novo mutations, chromosomal abnormalities or lethality
      in a significant fraction of the descendant cell population. The potential
      contribution of induced genomic instability to tumour and normal tissue response,
      and second tumours, after radiotherapy, is explored. RESULTS: The phenomenon of
      spontaneous genomic instability is well known in some rare genetic diseases (e.g.
      Gorlin's syndrome), and there is evidence in such cases that it can lead to a
      greater propensity for carcinogenesis (with shortened latency) which is enhanced
      after irradiation. It is unclear what role induced genomic instability plays in
      the response of normal individuals, but persistent chromosomal instability has
      been detected in vivo in lymphocytes and keratinocytes from irradiated normal
      individuals. Such induced genomic instability might play some role in tumour
      response in a subset of tumours with specific defects in damage response genes,
      but again its contribution to radiocurability in the majority of cancer patients
      is unclear. In normal tissues, genomic instability induced in wild-type cells
      leading to delayed cell death might contribute to more severe or prolonged early
      reactions as a consequence of increased cell loss, a longer time required for
      recovery, and greater residual injury. In tumours, induced genomic instability
      reflected in delayed reductions in clonogenic capacity might contribute to the
      radiosensitivity of primary tumours, and also to a lower incidence, longer
      latency and slower growth rate of recurrences and metastases. CONCLUSIONS: The
      evidence which is reviewed shows that there is little information at present to
      support these propositions, but what exists is consistent with their
      expectations. Also, it is not yet clear to what extent mutations associated with
      genomic instability, particularly gene polymorphisms, or other low penetrant gene
      mutations, contribute to the recognized spectrum of normal tissue
      radiosensitivity amongst cancer patients, or in the general population. Tests for
      such genetic modifications may help in the search for more accurate prognostic
      markers of response, which hopefully could be used in addition to other
      strategies to further improve the outcome for cancer patients given radiotherapy.

PMID- 11325440
TI  - Reirradiation of primary brain tumours: survival, clinical response and
      prognostic factors.
AB  - BACKGROUND AND PURPOSE: First, the aim was to determine the survival and quality
      of life after reirradiation of relapsing primary malignant brain tumours. The
      second aim was to assess the influence of a set of potentially prognostic factors
      on survival. MATERIALS AND METHODS: Forty-two patients received reirradiation for
      recurring primary brain tumours. The interval between the two consecutive
      treatments was at least 1 year. External beam irradiation for the initial and
      recurrent tumour was usually delivered with two opposing lateral fields or two
      wedged fields in orthogonal directions. The median physical doses of the first
      and second radiation course were 50 and 46 Gy, respectively. The median
      cumulative biological equivalent doses (BED) were 200.4 (alpha/beta = 2 Gy) and
      115.2 Gy (alpha/beta = 10 Gy). During follow-up, corticosteroid medication and
      the WHO-performance were registered at regular intervals. The radiological
      response was assessed by reviewing all available CT- and MRI-films. Potentially
      prognostic factors with respect to survival were evaluated by both univariate and
      multivariate analyses. RESULTS: A clinical response (i.e. clinical improvement)
      was seen in 24% of the patients. Of the evaluable patients, nearly one-third
      showed a complete (8%) or partial (22%) radiological response. The median overall
      survival (OS) and progression-free survival (PFS) after retreatment were 10.9 and
      8.6 months, respectively. By multivariate analysis, four independent prognostic
      factors for survival were identified: (1), the WHO-score before retreatment (P =
      0.002); (2), the length of the interval between treatments (P = 0.008); (3), the
      tumour histology; and (4), the response to initial treatment (P values, 0.04).
      The median survival times for patients with WHO-scores of 0-1 and > or = 2 were
      14.0 and 7.4 months, respectively. Patients with oligodendrogliomas had a median
      OS of 27.5 months, whereas patients with astrocytomas had a median OS of 6.9
      months after retreatment. Long-term complications of retreatment were seen in
      three patients, all of whom had a cumulative BED(2) of > 204 Gy (with alpha/beta
      = 2 Gy). The quality of life after retreatment, however, was well preserved in
      the majority of patients. They remained ambulant and capable of self-care until
      the time of progression which occurred after 8.6 months (median PFS).
      CONCLUSIONS: After an initial treatment with radiation up to tolerance levels of
      normal brain tissue, reirradiation of recurring primary brain tumours seems
      feasible. During the time until clinical progression, patients remained
      independent with a reasonable quality of life.

PMID- 11325441
TI  - Orbital lymphoma: radiotherapy outcome and complications.
AB  - BACKGROUND AND PURPOSE: Orbital non-Hodgkin's lymphomas (NHL) have traditionally
      been treated with radiation. Forty-eight patients presenting with orbital NHL
      were treated with radiation and were evaluated for local control, overall
      survival, cause-specific survival, and complications. MATERIALS AND METHODS:
      Forty-five patients had low-grade and 3 patients had intermediate-grade
      histologic findings. Orbit-only disease occurred in 22 patients, the conjunctiva
      in 16, both in five, and lacrimal gland only in five. Patient age ranged from 35
      to 94 years (median, 68). Ann Arbor stages were cIEA (34), cIIEA (six), cIIIEA
      (two), and cIVEA (six). Radiation doses ranged between 15 and 53.8 Gy (median,
      27.5 Gy). RESULTS: Follow-up ranged from 0.14 to 18.23 years (median, 5.35).
      Median overall survival and cause-specific survival were 6.5 and 15.5 years,
      respectively. Patients with clinical stage I or II disease had significantly
      better overall and cause-specific survival than patients with stage III or IV
      disease. Ten-year relapse-free survival in 41 patients with stage I or II disease
      was 66%. However, there was continued downward pressure on relapse-free survival
      out to 18 years. One local failure occurred. Twenty-five patients sustained acute
      complications. There were 17 minor and four major late complications. All major
      late complications occurred with doses more than 35 Gy. CONCLUSIONS: Excellent
      local control with radiation doses ranging from 15 to 30 Gy is achieved. Patients
      with stage I or II disease have better overall and cause-specific survival than
      patients with stage III or IV disease. Late relapse occurs in sites other than
      the treated orbit, even in patients with early-stage disease. Doses 35 Gy or
      higher result in significant late complications and are therefore not indicated
      for patients with low-grade tumors.

PMID- 11325442
TI  - Clinical stage IEA-IIEA orbital lymphomas: outcomes in the era of modern staging
      and treatment.
AB  - BACKGROUND AND PURPOSE: The present study examines outcomes in patients with
      primary orbital lymphomas who underwent complete staging. MATERIALS AND METHODS:
      From 1978 to 1997, 21 adult patients at the M.D. Anderson Cancer Center had stage
      IEA-IIEA orbital non-Hodgkin's lymphomas based on staging that included computed
      tomography scans. Sixteen (76%) patients had working formulation low-grade
      lymphomas, and five (24%) had aggressive lymphomas. Fourteen of 16 (88%) patients
      with low-grade lymphomas were treated with radiotherapy alone, and four of five
      (80%) patients with aggressive lymphomas were treated using combination
      chemotherapy with or without radiotherapy. Total radiotherapy doses ranged from
      30.0 to 40.0 Gy using daily 1.5-2.0 Gy fractions. RESULTS: The median follow-up
      was 84 months. For the low-grade lymphomas, the 5-year local control, progression
      free survival, and overall survival rates were 100, 100, and 92%, respectively.
      For the seven low-grade lymphomas treated with radiotherapy alone to 30.0 Gy in
      20 fractions, the 5-year local control, progression-free, and overall survival
      rates were 100, 100, and 75%, respectively. The 5-year incidence of
      complications, which were typically mild, in eyes irradiated to 30 Gy in 20
      fractions versus higher biologically effective doses were 25 and 38%,
      respectively (P = 0.62). Of the five patients with aggressive lymphomas, none of
      the four who underwent chemotherapy with or without radiotherapy relapsed (all
      four remain alive), whereas the one treated with radiotherapy alone for stage IEA
      disease experienced a distant relapse. CONCLUSIONS: In patients with low-grade
      lymphomas, a good therapeutic ratio was obtained with low-dose radiotherapy
      alone. In patients with aggressive lymphomas, chemotherapy with or without
      radiotherapy resulted in excellent local control, progression-free survival, and
      overall survival; however, the statistical power was limited.

PMID- 11325443
TI  - The treatment of choroidal melanoma with 198 Au plaque brachytherapy.
AB  - BACKGROUND: Seventy-nine consecutive patients with primary choroidal melanoma
      were treated with 198 Au plaque brachytherapy at the British Columbia Cancer
      Agency (BCCA) between 1992 and 1998 with perioperative ultrasound to confirm
      plaque placement. Seventy-seven of the 79 patients were analyzable for this
      study. RESULTS: Five year actuarial disease specific survival, enucleation free
      survival, and local control are 95, 94, and 98%, respectively. There were four
      melanoma related deaths, all secondary to liver metastases. CONCLUSIONS: The BCCA
      experience in selected patients with choroidal melanomas treated with 198Au
      plaque brachytherapy has resulted in excellent survival and local control with
      minimal significant toxicity while preserving the globe. Our results using 198 Au
      seeds are comparable to other series using 125I, 60Co, and 106Ru at other
      centers.

PMID- 11325444
TI  - The efficacy of Xialine in patients with xerostomia resulting from radiotherapy
      for head and neck cancer: a pilot-study.
AB  - Changes in subjective sensations due to xerostomia before and after
      administration of Xialine, a xanthan gum-based saliva substitute, were evaluated
      in 30 patients with radiation-induced xerostomia using the QLQ-H&N35. Xerostomia
      in general decreased with both Xialine and placebo to almost the same degree. A
      trend was seen for Xialine to improve problems with speech and senses.

PMID- 11325445
TI  - Radiotherapy for advanced adenoid cystic carcinoma: neutrons, photons or mixed
      beam?
AB  - PURPOSE: To compare retrospectively radiotherapy with neutrons, photons, and a
      photon/neutron mixed beam in patients with advanced adenoid cystic carcinoma of
      the head and neck. Local control, survival, distant failure, and complications
      were analyzed. MATERIALS AND METHODS: Between 1983 and 1995, 75 patients with
      inoperable, recurrent, or incompletely resected adenoid cystic carcinoma of the
      head and neck received radiotherapy that consisted of either fast 14.1 MV DT
      neutrons (median dose 16 neutron Gy), linac-based photon irradiation (median dose
      64 photon Gy), or both (median dose 8 neutron Gy and 32 photon Gy). Follow-up
      ranged from 1 to 160 months (median 51 months), and the surviving patients had a
      minimum follow-up of 3 years at the time of analysis. RESULTS: The actuarial 5
      year local control was 75% for neutrons, and 32% for both mixed beam and photons
      (P = 0.015, log-rank). This advantage for neutrons in local control was not
      transferred to significant differences in survival (P > 0.1). The survival is
      dictated by the tumor diseases due to distant metastases occurring in 29 (39%) of
      the 75 patients. Positive lymph nodes were the only significant factor (P =
      0.001) associated with the development of distant metastases although negative
      lymph nodes did not predict absence of distant metastases, but predicted a delay
      of occurrence. In multivariate analysis postoperative radiotherapy (P = 0.003)
      and small tumor size (P = 0.01) were associated with high local control, while
      primary therapy (P = 0.006) and negative lymph nodes (P = 0.01) were associated
      with longer survival. While acute toxicity was similar in all three radiotherapy
      groups, severe late grade 3 and 4 toxicity tended to be more prevalent (P > 0.1)
      with neutrons (19%) than with mixed beam (10%) and photons (4%). CONCLUSION: Fast
      neutron radiotherapy provides higher local control rates than a mixed beam and
      photons in advanced, recurrent or not completely resected adenoid cystic
      carcinoma of the major and minor salivary glands. Neutron radiotherapy can be
      recommended in patients with bad prognosis with gross residual disease (R2), with
      unresectable tumors, or inoperable tumors. The type of radiation does not impact
      survival, which is dominated by the high number of distant metastases.

PMID- 11325446
TI  - Beam-orientation optimization of intensity-modulated radiotherapy: clinical
      application to parotid gland tumours.
AB  - BACKGROUND AND PURPOSE: An optimization algorithm has been developed to determine
      the best beam-arrangement for a small number of intensity-modulated radiotherapy
      (IMRT) fields. The algorithm is designed to avoid, if possible, beam-orientations
      that pass through organs-at-risk (OARs) with low radiation tolerance. MATERIALS
      AND METHODS: An independent, fast IMRT algorithm based on the Bortfeld algorithm
      was developed to determine the profile of the intensity-modulated beams (IMBs)
      for each beam-arrangement and a fast-simulated-annealing algorithm finds the
      'optimal' beam-arrangement. The final beam-arrangement was transferred to the
      CORVUS (NOMOS Corporation) treatment planning system, and the IMBs were re
      optimized for comparison with a standard nine-field, equi-spaced arrangement. The
      algorithm has been initially tested on a single example patient, with a parotid
      gland carcinoma. RESULTS: The nine-field, IMRT plan for an example patient with a
      parotid gland tumour significantly reduced the dose to the cochlea compared with
      the conformal radiotherapy plan. In addition, the planning-target-volume (PTV)
      homogeneity was improved, but the plan produced a higher dose to the
      contralateral parotid (73% of the OAR received more than 6 Gy). The beam
      orientation optimization algorithm produced a three-field plan that greatly
      reduced the dose to the contralateral parotid (maximum dose of 2 Gy), whilst
      maintaining the PTV dose homogeneity and the reduced cochlear dose of the nine
      field plan. Some changes in the dose to the other OARs, namely the brain and the
      oral cavity, were seen, but were deemed not to be clinically significant.
      CONCLUSIONS: In conclusion, IMB-orientation optimization for head and neck
      treatment sites can produce improvements in treatment plans with only a few
      fields.

PMID- 11325447
TI  - TP53 mutation is related to poor prognosis after radiotherapy, but not surgery,
      in squamous cell carcinoma of the head and neck.
AB  - BACKGROUND AND METHODS: TP53 gene-mutation and expression of p53 have been
      described to influence the radiosensitivity of tumour cells from head and neck
      carcinomas. The present study was performed to evaluate whether TP53 mutation may
      influence the clinical outcome of head and neck cancer patients treated with
      radiotherapy or surgery. MATERIALS AND METHODS: DNA was extracted from formalin
      fixed paraffin-embedded tissue sections from primary biopsies taken before
      radiotherapy. Gene mutations (in exons 5-9) were identified using denaturing
      gradient gel electrophoresis (DGGE) as the initial scanning procedure and
      characterized by sequencing. Patients were treated with primary radiotherapy or
      surgery alone. Treatment was given according to the DAHANCA schedules with 5 or 6
      weekly fractions (2 Gy) of radiotherapy (66-68 Gy). Most patients were also
      treated with the hypoxic radiosensitizer Nimorazole. The results are reported as
      5-year actuarial values, and differences estimated by log-rank analysis. RESULTS:
      The present analysis is based on 114 patients with squamous cell carcinoma of the
      larynx, pharynx and oral cavity diagnosed between March 1992 and October 1996.
      Ninety patients received primary radiotherapy alone and 21 were treated with
      surgery. TP53 mutations were found in 45 patients (39%) and in patients receiving
      radiotherapy, TP53 mutation was highly associated with poor prognosis. Loco
      regional control rates (5-year actuarial values) for TP53 mutation was 29 vs. 54%
      for TP53 wildtype (P < 0.01). For disease-free survival the corresponding values
      were 13 and 38% (P < 0.01), respectively. The correlations were not found to be
      related to specific subtypes of mutations (e.g. missense mutations affecting DNA
      contact or Zn-binding regions) but rather to the presence of any mutation at all.
      In contrast, TP53 mutation did not influence the response to surgery.
      CONCLUSIONS: A strong relationship was observed between TP53 mutation and poor
      prognosis (increased risk of loco-regional failure and death) in head and neck
      cancer patients given primary radiotherapy but not surgery.

PMID- 11325448
TI  - No evidence for a different magnitude of the time factor for continuously
      fractionated irradiation and protocols including gaps in two human squamous cell
      carcinoma in nude mice.
AB  - BACKGROUND AND PURPOSE: To study whether the magnitude of the time factor is
      different for continuously fractionated irradiation and for fractionation
      protocols including gaps. MATERIALS AND METHODS: Two human head and neck squamous
      cell carcinomas (SCCs), FaDu and GL, were transplanted subcutaneously into the
      right hindleg of NMRI (nu/nu) mice and irradiated with 30 fractions under ambient
      conditions within 2, 6 and 10 weeks. Irradiations within 6 and 10 weeks were
      given either as a continuous course or with a mid-course gap of 3 weeks. The end
      point of the experiments was local tumor control at day 120 (FaDu) or day 180
      (GL) after the end of treatment. RESULTS: In FaDu tumors, two experimental
      cohorts (A, B) yielded significantly different results and were analyzed
      separately. In cohort A, the tumor control dose 50% (TCD50) increased from 37 to
      89 Gy when the treatment time of continuous fractionated irradiation was extended
      from 2 to 10 weeks. The recovered dose/day (D(r)) was 0.98 Gy (95% confidence
      interval, 0.72; 1.27). In cohort B, the TCD50 increased from 35 to 63 Gy, and the
      D(r) was 0.51 Gy (0.24; 0.75). In GL tumors, the TCD50 for continuously
      fractionated irradiation increased from 41 to 48 Gy. This increase was not
      significant, and the D(r) was 0.15 Gy (0; 0.30). None of the TCD50 and D(r)
      values obtained in both tumor models for continuous irradiation vs. irradiation
      with a gap were significantly different. CONCLUSIONS: Prolongation of the overall
      treatment time of fractionated irradiation resulted in a pronounced decrease of
      local control in human FaDu SCC and little decrease of local control in human GL
      SCC. No evidence was found that the magnitude of the time factor in these tumors
      is different for continuous fractionation or fractionation protocols including
      gaps.

PMID- 11325449
TI  - Localized squamous-cell cancer of the esophagus: retrospective analysis of three
      treatment schedules.
AB  - BACKGROUND AND PURPOSE: A retrospective study comparing chemotherapy and
      radiation, esophagectomy alone versus preoperative radiochemotherapy and surgery
      in localized squamous-cell esophageal carcinoma. MATERIALS AND METHODS: Between
      1989 and 1995, 139 patients (40 stage I, 77 stage IIA and 22 stage IIB according
      to the UICC 78 TNM classification) were treated in two different institutions.
      They were divided into three groups according to the treatment proposed: E group
      (treatment by esophagectomy; n = 30), RCT+E group (treatment by preoperative
      radiochemotherapy and esophagectomy; n = 46), RCT group (treatment by
      radiochemotherapy; n = 63). Factors like age, tumor localization and stage were
      similar in all groups. An intention to treat analysis was made. RESULTS: The E
      group showed no postoperative mortality, while in the RCT+E group, the surgery
      mortality was 12.8%. The mortality after RCT was 1.7%. After preoperative
      radiochemotherapy, a pathological complete response was observed in 25% of cases
      and the curative resection rate was higher (82% after RCT + E versus 60% after
      E). The 5-year survival difference between the three groups was not relevant (E
      group, 12.6%; RCT group, 25.8%; RCT + E group, 38.7%). The median survival was
      29, 24 and 28.5 months, respectively. The event-free survival was identical for
      the E group and the RCT group. For patients treated by radiochemotherapy, local
      and/or distant relapses were significantly reduced by esophagectomy (relapses
      occurred in 51% of patients in the RCT + E group versus 75% in the RCT group, P =
      0.017). Palliative care (dilatations, prosthesis, gastrostomy or jejunostomy) to
      improve dysphagia was necessary for 38% of patients treated by exclusive
      radiochemotherapy versus 11% of patients treated by surgery (P = 0.001).
      CONCLUSIONS: Treatments by esophagectomy or radiochemotherapy were not
      significantly different. Preoperative radiochemotherapy and surgery lead to a
      higher survival rate than exclusive radiochemotherapy, however, with a high
      postoperative mortality rate. This study suggests the relevance of a prospective
      randomized trial to compare RCT+E and RCT alone.

PMID- 11325450
TI  - Ionizing radiation affects 26s proteasome function and associated molecular
      responses, even at low doses.
AB  - BACKGROUND AND PURPOSE: Ionizing radiation is known to activate certain signal
      transduction pathways, the regulation of which could involve post-transcriptional
      as well as transcriptional mechanisms. One of the most important post
      transcriptional pathways in eukaryotic cells is the ATP- and ubiquitin-dependent
      degradation of proteins by the 26s proteasome. This process controls initiation
      of many cellular stress responses, as well as inflammatory responses under
      control of the transcription factor NF-kappaB. The literature on the relationship
      between radiation and inflammation seems somewhat paradoxical. At high doses,
      radiation is generally pro-inflammatory. On the other hand, low dose radiation
      has a long history of use in the treatment of inflammatory disease. This suggests
      the involvement of multiple mechanisms that may operate differentially at
      different dose levels. MATERIALS AND METHODS: In this paper, the ability of
      different doses of ionizing radiation to directly affect 26s proteasome activity
      was tested in ECV 304 cells. Proteasome activity, IkappaBalpha protein levels,
      and NF-kappaB activation were monitored. RESULTS: Inhibition of chymotrypsin-like
      20s and 26s proteasome activity was observed immediately after low- and high-dose
      irradiation either of cells or purified proteasomes. The inhibitory effect was
      independent of the availability of the known endogenous proteasome inhibitor heat
      shock protein 90 (hsp90). Levels of IkappaBalpha, a physiological 26s proteasome
      substrate, were increased only at low doses (0.25 Gy) and unaltered at higher
      doses whereas only the highest doses (8 and 20 Gy) activated NF-kappaB.
      CONCLUSIONS: We conclude that the proteasome is a direct target of ionizing
      radiation and suggest that inhibition of proteasome function provides a molecular
      framework within which low dose anti-inflammatory effects of radiation, and
      radiation-induced molecular responses in general, should be considered.

PMID- 11325451
TI  - Epithelial cells in the peripheral blood of patients with cancer of the head and
      neck: incidence, detection and possible clinical significance.
AB  - In this study amplification of cytokeratin-19 mRNA by Reverse transcriptase
      polymerase chain reaction (RT-PCR) was used to detect circulating tumor cells in
      the peripheral blood of patients with cancer of the head and neck before, during
      and after radiation therapy. Detection of cytokeratin-19-positive cells coincided
      with local failure, distant metastasis and anemia.

PMID- 11325452
TI  - Local control of T3N0 glottic carcinoma by 60 Gy given over five weeks in 2.4 Gy
      daily fractions. One more point on the biological effective dose (BED) curve.
AB  - Seventy patients with T3N0 glottic cancer who received a total dose of 60 Gy in
      twenty-five 2.4 Gy daily fractions over 5 weeks had an initial post radiation
      primary recurrence free rate of 65% at 5 years. This provides one more point for
      the dose response for T3 glottic cancer Radiother Oncol (1999) 15.

PMID- 11325453
TI  - Relation of erythrocyte and iron indices to oral cancer growth.
AB  - BACKGROUND AND PURPOSE: Anaemia is known to influence prognosis of head and neck
      cancer patients, but how anaemia and tumour growth influences each other is not
      clear. The present study investigates the relation of erythrocyte and iron
      indices of oral cancer patients to primary tumour size (Tsize), invasiveness and
      lymph node involvement. MATERIALS AND METHODS: The haemoglobin (Hb), erythrocyte
      count (RBC), packed cell volume (PCV), mean corpuscular volume (MCV), mean
      corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC),
      Serum iron (SFe), transferrin iron-binding capacity (TIBC) and transferrin
      saturation (%Fe) were evaluated in 217 untreated patients with epidermoid cancer
      of the bucco-gingivo-palatine area. The association of erythrocyte and iron
      indices with sex, tumour size groups, invasion of adjacent structures and lymph
      node involvement, as well as the relation of SFe to Hb were analyzed. RESULTS:
      Most of the patients were anaemic in terms of Hb (63%), RBC (43%) and PCV (48.4%)
      but almost all had normal or higher MCH (97.3%) and MCV (93.3%) though MCHC was
      less than normal in 70.7%. Normal or higher SFe was seen in nearly 70% and TIBC
      in 45% of patients. Hb, RBC and PCV were significantly lower in women, but there
      was no difference between men and women in the case of MCV, MCH and MCHC. Primary
      tumour size showed negative association with Hb, RBC and PCV but positive
      association with MCH (< 2 cm: 29.7 pg; 2-4 cm: 31.4 pg; > 4 cm: 31. 7 pg; P =
      0.04) and MCHC (< 2 cm: 29.9; 2-4 cm: 31.5; > 4 cm: 32.1; P = 0.006). MCV, SFe,
      TIBC and %Fe did not show any relation to primary tumour size. None of the
      indices had any relation to invasion of adjacent structures or lymph node
      involvement. MCH, MCHC and MCV were not different in men and women but women had
      significantly lower Hb, RBC and PCV. The SFe showed poor correlation with Hb.
      CONCLUSIONS: The negative association of Hb, RBC and PCV with tumour size is most
      likely due to chronic RBC destruction, probably tumour induced, with the products
      of haemolysis such as polyamines, glutathione, iron, etc., promoting tumour
      growth, and the positive association with MCH and MCHC reflects compensatory
      regeneration attempts by bone marrow. Lack of relation between the iron indices
      and tumour parameters and the poor correlation between SFe and Hb is probably due
      to utilization of iron by both bone marrow and tumours. Lack of difference in MCH
      and MCHC between men and women obviates the need of using separate cut-off values
      for the two sexes, unlike Hb, RBC and PCV. The study suggests that anaemia in
      oral cancer patients represents a tumour-host interaction and that evaluation of
      all erythrocyte indices should be part of research on cancer related anaemia.

PMID- 11325454
TI  - Clinical thermometry, using the 27 MHz multi-electrode current-source
      interstitial hyperthermia system in brain tumours.
AB  - BACKGROUND AND PURPOSE: In interstitial hyperthermia, temperature measurements
      are mainly performed inside heating applicators, and therefore, give the maximum
      temperatures of a rather heterogeneous temperature distribution. The problem of
      how to estimate lesion temperatures using the multi-electrode current-source
      interstitial hyperthermia (MECS-IHT) system in the brain was studied. MATERIALS
      AND METHODS: Temperatures were measured within the electrodes and in an extra
      catheter at the edge of a 4 x 4 x 4.5 cm(3) glioblastoma multiforme resection
      cavity. From the temperature decays during a power-off period, information was
      obtained about local maximum and minimum tissue temperatures. The significance of
      these data was examined through model calculations. RESULTS: Maximum tissue
      temperatures could be estimated roughly by switching off all electrodes for about
      5 s. Model calculations showed that the minimum tissue temperatures near a
      certain afterloading catheter correspond well with the temperature of the
      applicator inside, about 1 min after this applicator was switched off.
      CONCLUSIONS: Although the electrode temperatures read during heating are not
      suitable to assess the temperature distribution, it is feasible to heat the brain
      adequately using the MECS-IHT system with extra sensors outside the electrodes
      and/or application of decay methods.

PMID- 11325455
TI  - Clarification of hemispheric modulatory influences on bilateral electrodermal
      activity, frontal asymmetry and mood.

PMID- 11325456
TI  - Associations between EEG asymmetries and electrodermal lability in low vs. high
      depressive and anxious normal individuals.
AB  - In order to investigate one aspect of cortical-autonomic control, cortical
      activation asymmetries, measured by EEG, were related to activity of the
      sympathetic nervous system, measured by EDA (electrodermal lability, number of
      spontaneous fluctuations), in two large samples. Since it may help to explain the
      participation of psychological factors in the development of various somatic
      complaints and disorders, we examined whether inter-individual differences in
      autonomic nervous system regulation may exist that are related to stress/anxiety
      and depression within the normal range. Results demonstrate substantial
      modifications of functional hemisphere asymmetries in the modulation of EDA by
      these emotional factors and suggest that activation asymmetries in orbital and
      dorsolateral frontal regions reflect two different cortical sub-systems
      regulating electrodermal activity. The findings may, to some extent, provide an
      explanation for contradictory results in previous studies and may encourage
      research in psychosomatics and other clinical fields (e.g. schizophrenia).

PMID- 11325457
TI  - Perceptual learning: psychophysical thresholds and electrical brain topography.
AB  - We studied perceptual learning by determining psychophysical discrimination
      thresholds for visual hyper acuity targets (vernier stimuli) as a function of
      stimulus orientation. One aim was to relate perceptual improvements to changes of
      electrophysiological activity of the human brain. A group of 43 healthy adults
      participated in a psychophysical experiment where vernier thresholds for vertical
      and horizontal vernier targets were compared. In 16 subjects thresholds were
      measured for each orientation twice at an interval of 25 min. Between threshold
      estimations, evoked brain activity was recorded from 30 electrodes over the
      occipital brain areas while the subjects observed appearance and disappearance of
      supra-threshold vernier offsets. Mean evoked potentials were computed for the
      first and second 600 stimulus presentations, and the scalp topography of
      electrical brain activity was analyzed. Vertically oriented stimuli yielded
      significantly better performance than horizontal targets, and thresholds were
      significantly lower in the second half of the experiment, i.e. after prolonged
      viewing of stimuli. The improvements in discrimination performance were specific
      for stimulus orientation and did not generalize. Learning effects were also
      observed with electrical brain activity, and field strength of the potentials
      increased significantly as a function of time. Scalp topography of the evoked
      components was significantly affected indicating a shift of activation between
      different neuronal elements induced by perceptual learning.

PMID- 11325458
TI  - The initial orienting response during human REM sleep as revealed by the N1
      component of auditory event-related potentials.
AB  - The large N1 wave of the auditory event-related potentials (ERPs) typically
      occurring to the first stimulus after a long silent interval seems to be
      associated with the involuntary initial-orienting response. Since the mechanisms
      involved in the generation of this brain response are assumed to be activated
      automatically, the present study aims at determining whether this
      electrophysiological response can also be elicited during human REM sleep, the
      sleep stage considered most sensitive to external stimuli. To achieve this goal,
      the auditory N1 wave was analyzed in wakefulness and REM sleep for frequency
      deviant tones delivered in several positions (1, 2, 4 and 6) within homogenous
      stimulus trains separated by different intervals of silence (3, 6 and 9 s), the
      intra-train stimulus interval being 600 ms. A significant increment in the
      amplitude of the N1 component for the first deviant tone, as compared with
      deviants delivered in remaining positions, was observed in both brain states,
      independently of the inter-train interval length. This result cannot be explained
      by a release-from-refractoriness effect, since only one deviant was presented in
      each train and the inter-deviant interval hardly changed from one train to
      another. The increase in N1 to the first stimulus of the train, probably due to
      the contribution of the neuronal elements responsible for the supratemporal and
      non-specific components, may be explained by changes in the silent interval,
      rather than by variations in the stimulus frequency. The enhanced N1 could be
      reflecting a general increase in sensory sensitivity associated with the arousal
      factor of the orienting response. These findings suggest that the brain maintains
      the potential ability to trigger the brain events responsible for the OR
      elicitation, even during REM sleep.

PMID- 11325459
TI  - Source localization of EEG activity during hypnotically induced anxiety and
      relaxation.
AB  - The engagement of different brain regions which implement subjectively
      experienced emotional states in normals is not completely clarified. Emotional
      states can conveniently be induced by hypnosis-based suggestions. We studied
      brain electric activity during hypnotically induced anxiety and relaxation in 11
      right-handed normals (5 males, 6 females, mean age 26.5+/-7.6 years). After
      induction of light hypnosis, anxiety and then relaxation was suggested using a
      standardized text (reverse sequence in half of the subjects). Nineteen-channel,
      eyes-closed EEG (20 artifact-free s/subject) was analyzed (source localization
      using FFT approximation and low resolution electromagnetic tomography, LORETA).
      Global tests revealed the strongest difference (P<0.005) between EEG source
      gravity center locations during the two emotional states in the excitatory beta-2
      EEG frequency band (18.5-21 Hz). Post hoc tests showed that the sources were
      located more right during anxiety than during relaxation (P=0.01). LORETA
      specified that anxiety showed maximally stronger activity than relaxation in
      right Brodmann area 10, and relaxation showed maximally stronger activity than
      anxiety in left Brodmann area 22. Clearly, the two induced emotional states were
      associated with activity of different neural populations. Our results agree with
      reports on brain activity shifted to the right (especially fronto-temporal)
      during negative compared with positive emotions, and support the role of beta-2
      EEG frequency in emotional states.

PMID- 11325460
TI  - The specificity of infant emotional expression for emotion perception.
AB  - Attachment theory emphasizes the role of negative emotional expression in infancy
      for establishing proximity to and care of the caregiver. According to Lang's
      biphasic model of emotions protective reflexes (e.g. startle response) are primed
      if a defensive motivational set is activated. The aim of the study was to examine
      whether the perception of an infant emotional expression can prime such defensive
      behavior. The sample consisted of 48 university students. Startle reflex,
      corrugator and zygomatic EMG activity and subjective ratings of valence and
      arousal were assessed as a response to presentation of pictures of different
      emotional valence. Affective startle modulation was obtained when probes were
      presented during pictures of the International Affective Pictures System
      replicating previous findings. By contrast, negative infant emotion pictures did
      not prompt an augmentation of the startle response, although both the subjective
      ratings and the mimic EMG activity indicated a clear differentiation between
      negative and positive infant pictures. This pattern of findings was found only in
      a between-subject design, but not when the two picture sets were presented in the
      same session, indicating an interference of contrasting content of pictures.

PMID- 11325461
TI  - Mood state and cardiovascular response in active coping with an affect-regulative
      challenge.
AB  - We investigated the impact of mood states and task valence on cardiovascular
      reactivity in active coping. According to previous research, subjective demand is
      higher in a negative mood than in a positive mood, and cardiovascular adjustments
      are a function of subjective demand. Thus, we expected stronger cardiovascular
      reactivity in a negative mood than in a positive mood during task performance.
      University students (n=60) were first induced into either a positive or negative
      mood state via exposure to music. They then performed either a pleasant or
      unpleasant scenario completion task that provided opportunities for mood
      regulation. No effects were found on cardiovascular reactivity during the mood
      inductions. However, during task performance, systolic and diastolic blood
      pressure reactivity was stronger in a negative than in a positive mood. Task
      valence, which was successfully manipulated according to a verbal manipulation
      check, and post-performance mood changes had no significant impact. Results are
      interpreted as a further demonstration of the impact of mood valence on
      cardiovascular reactivity in active coping.

PMID- 11325462
TI  - Sleep pattern and daytime differences in the electromyographic activity and
      peripheral temperature.
AB  - For a long time, it has been said that most individuals sleep an average of 8 h.
      However, there are subjects that usually sleep less than 6 h (the ones placed
      under the label of short sleep pattern, SSP) and subjects that sleep more than 8
      h (those classified by the long sleep pattern, LSP). Starting from this division,
      several studies have been carried out in order to establish possible differences
      in terms of psychological and physiological variables. This study is aimed at
      assessing the differences that might occur in electromyographic activity and
      temperature in long, medium and short sleep pattern subjects at two moments in
      the day. From a 300-subject sample, 17 long sleep pattern, nine medium sleep
      pattern and eight short sleep pattern subjects were selected. The physiological
      variables were assessed during a constant stimulation task in the morning
      (between 09.00 and 10.00 h) and in the evening (between 19.00 and 20.00 h). The
      inter-group analysis showed that the long sleep pattern and the short sleep
      pattern subjects differed in terms of electromyographic activity in the morning.
      This same analysis indicated that only long sleep pattern subjects showed changes
      in electromyographic activity over two measurements taken in the same day. The
      results point out that long sleep pattern subjects show more sensitivity towards
      changes, and that sensitivity is expressed in a different manner, depending on
      the time of the day.

PMID- 11325463
TI  - Source localisation of 62-electrode human laser pain evoked potential data using
      a realistic head model.
AB  - Laser evoked potentials (LEPs), elicited by painful laser stimulation of the
      right forearm, were recorded from 62 electrodes in a single healthy subject. The
      positions of the electrodes on the scalp were co-registered with the subject's
      structural magnetic resonance image (MRI) of the brain. Spatio-temporal dipole
      modelling, using a head model derived from the MRI, estimated sources in left
      posterior cingulate, posterior parietal and anterior insular cortices. The
      parietal source peaked in activity at 260 ms, which explained the N1/N2 peaks of
      the LEPs. The cingulate source was the most strongly activated, at 400 ms, and
      accounted for the P2 LEP component. The insular source showed late, prolonged
      activation, peaking in magnitude at 850 ms. This is the first study to report
      scalp-recorded LEP generators in posterior parietal and insular cortices.
      Although these sources require replication, they are consistent with other
      functional imaging studies.

PMID- 11325464
TI  - Roles of the hinge region and the DNA binding domain of the bovine papillomavirus
      type 1 E2 protein in initiation of DNA replication.
AB  - The bovine papillomavirus (BPV-1) E2 protein is the regulator of extrachromosomal
      replication of papillomaviruses. The mutants with C-terminal truncations and in
      frame internal deletions were constructed to study the role of structural domains
      of E2 in the initiation of DNA replication. We show that the replication
      initiation function of E2 is absolutely dependent on the ability of the protein
      to bind to DNA. Our study also confirms the borders of the functional domains of
      the E2 protein; residues 1-192 form the activation domain and residues 310-410
      the DNA binding-dimerization domain. Some critical length and flexibility, but
      not the particular amino acid sequence between these two functional domains is
      required for the activity of the protein to support replication. The hinge
      region, including the major phosphorylation sites of E2, is also dispensable for
      the mediation of attachment of the BPV1 genome to the mitotic chromosomes.

PMID- 11325465
TI  - Variations within hepatitis C virus E2 protein and response to interferon
      treatment.
AB  - To determine whether the hepatitis C virus (HCV) E2 PePHD sequence (aa 659-670;
      PKR-eIF2alpha phosphorylation homology domain) is the determinant for the
      response of interferon treatment, we have analyzed PePHD sequences in HCV
      infected patients who had received interferon-alfa treatment. The PePHD sequence
      from all (6/6) of the patients, who are non- or partial responders to the
      interferon treatment, is the wild-type sequence (RSELSPLLL-TT, consensus sequence
      of HCV-1a and HCV-1b). However, there are sequence variations from more than half
      (5/9) of the patients, who are complete responders to the treatment. We have also
      analyzed the NS5A ISDR sequence (aa 2209-2248, interferon sensitivity-determining
      region) variation in HCV-1b-infected patients. No such correlation has been
      observed. Thus, our data suggest that HCV E2 should play a more important role
      than NS5A in determining the interferon responses.

PMID- 11325466
TI  - Expression of canine interferon-gamma by a recombinant vaccinia virus and its
      antiviral effect.
AB  - A recombinant vaccinia virus-expressing canine interferon (IFN)-gamma (vv/cIFN
      gamma) was constructed. In rabbit kidney (RK13) and canine A72 cells infected
      with vv/cIFN-gamma, IFN activity was detected in the culture supernatants of both
      cell types. Canine IFN-gamma was also detected in both cell extracts by Western
      blot. The activity of the recombinant canine IFN-gamma in RK13 cells was higher
      than that in A72 cells. The vv/cIFN-gamma could not grow in A72 cells at a low
      multiplicity of infection, probably due to the antiviral activity of the canine
      IFN-gamma produced. Although exogenous IFN-gamma did not inhibit the growth of
      vaccinia virus, addition of anti-canine IFN-gamma serum recovered the growth of
      the vv/cIFN-gamma on A72 cells in a dose-dependent manner. These results suggest
      that the growth of vv/cIFN-gamma was inhibited by IFN-gamma produced in a
      paracrine and autocrine manner. In addition, the recombinant canine IFN-gamma
      inhibited the multiplication of canine herpesvirus, pseudorabies virus and canine
      adenovirus type 1 in Madin-Darby canine kidney cells. The antiviral effect of
      canine IFN-gamma was more effective than that of canine IFN-beta. From the
      present studies, we concluded the recombinant virus may be a useful suicide viral
      vector.

PMID- 11325467
TI  - Complete nucleotide sequence of a group A avian rotavirus genome and a comparison
      with its counterparts of mammalian rotaviruses.
AB  - The nucleotide sequences encoding four structural proteins (VP1-4) and six
      nonstructural proteins (NSP1-6) of avian rotavirus PO-13 were determined. Based
      on the results of earlier sequencing studies [Ito et al., 1995, Sequence analysis
      of cDNA for the VP6 protein of group A avian rota viruses. Arch. Vriol. 140, 605
      612; Rohwedder et al., 1997, Chicken rotavirus Ch-1 shows a second type of avian
      VP6 gene, Virus Genes 15, 65-71; Rohwedder et al., 1997, Bovine rotavirus 993/83
      shows a third subtype of avian VP7 protein, Virus Genes 14, 147-151],
      determination of PO-13 genome sequence has been completed. The PO-13 genome is
      18845 nucleotides in length. It is 290 nucleotides longer than the genome of
      SA11. The amino acid sequence homology between PO-13 and mammalian rotaviruses
      ranged from 76-77% (VP1) to 16-18% (NSP1). The features of gene and amino acid
      sequence were compared with those of the corresponding protein of mammalian
      rotaviruses. Based on results of the phylogenetic analyses of NSP1, we speculate
      that an ancestral rotavirus could have separated into groups A, B and C
      rotaviruses at an early evolutionary stage and that group A rotavirus separated
      into mammalian and avian rotaviruses with host evolution.

PMID- 11325468
TI  - Complete nucleotide sequences of the RNAs 2 of German isolates of grapevine
      fanleaf and Arabis mosaic nepoviruses.
AB  - The RNAs 2 of an Arabis mosaic virus (ArMV) and a grapevine fanleaf virus (GFLV)
      isolate, originating from South West of Germany near Neustadt an der Weinstrasse
      (NW), were sequenced. They are 3820 and 3775 nucleotides long respectively, and
      both contain one open reading frame encoding a polypeptide of 1110 amino acids.
      Their 5' non-coding regions contain conserved and repeated sequences, which are
      able to form stem-loop structures. Nucleotide sequence comparisons between the
      full-length RNAs 2 revealed homology levels of 84 and 82% between the ArMV-NW and
      the ArMV-L and -U, respectively, 90% between GFLV-NW and GFLV-F13, and 72%
      between ArMV-NW and GFLV-NW. Amino acid sequence comparisons showed that the
      greatest difference was found between the 2A proteins of the different ArMV
      isolates, the 2A protein of the ArMV-NW showing more similarity to the 2A protein
      of GFLV-NW than to those of ArMV-L2 or -U2.

PMID- 11325469
TI  - Immunoregulatory role of secreted glycoprotein G from respiratory syncytial
      virus.
AB  - The secretory glycoprotein (Gs) of respiratory syncytial virus (RSV) was enriched
      and investigated for its effects on T cells specific for RSV and unrelated
      antigens. Gs exhibited a dose dependent suppression of lymphoproliferative
      responses in peripheral blood mononuclear cells (PBMCs), specific for
      mycobacterial lysates or tetanus toxoid. However, Gs did not inhibit live RSV
      specific T cell responses. These results suggest that Gs may suppress immune
      response to unrelated antigens, but should not interfere with the overall
      development of RSV specific immunity.

PMID- 11325470
TI  - Simian retrovirus vectors for gene transfer in nonhuman primate cells.
AB  - We have recently identified and sequenced a molecular clone of the serogroup 2
      simian retrovirus (SRV), D2/RHE/OR/V1, that retains an enhanced ability to infect
      specific T cell lines. In this report, using deletion mutagenesis, we localized
      the psi packaging signal, necessary for packaging of D2/RHE/OR/V1 particles, to
      the genomic region 345-650, which comprises the 5' intergenic region (IR) and the
      extreme 5' portion of the gag gene. To build an SRV-based gene transfer system
      and to reduce the possibility of recombination and regeneration of replication
      competent viruses, we constructed split-genome D2/RHE/OR/V1 plasmid recombinants
      containing distinct and non-overlapping retroviral gene regions and several
      replacement components. For the retrovirus gene transfer vehicle, we deleted the
      D2/RHE/OR/V1 structural genes and substituted a cassette including the psi
      packaging region, the beta-galactosidase reporter gene, and the 3' IR. Both
      packaging cell recombinants were used to generate stable monkey packaging cell
      lines; the gene transfer vehicle was subsequently transfected into the packaging
      cell lines, and replication-defective viruses were recovered for subsequent
      infection into fresh monkey cells. Successful infection by the recovered viruses
      verifies the potential efficacy of the SRV-based system as a research tool for
      gene transfer of heterologous genes into nonhuman primate cells.

PMID- 11325471
TI  - The hemagglutinin-neuraminidase protein of peste des petits ruminants virus is
      biologically active when transiently expressed in mammalian cells.
AB  - The genes coding for the surface glycoproteins hemagglutinin-neuraminidase (HN)
      of the peste des petits ruminants virus (PPRV) and hemagglutinin (H) of
      rinderpest virus (RPV) were cloned in a cytomagalovirus promoter driven
      expression vector and expressed transiently in mammalian cells. The protein
      expression was apparent 24 h after transfection and the expressed proteins were
      detected at the cell surface. The transiently expressed PPRV HN protein was found
      to be biologically active in possessing hemadsorption and neuraminidase
      activities. On the other hand, RPV H protein exhibited neuraminidase activity but
      was deficient in hemadsorption activity. The substrate specificity of the
      neuraminidase activity of these two proteins differed distinctly. The presence of
      neuraminidase activity in both PPRV HN and RPV H proteins is unusual among
      members of the morbillivirus genus.

PMID- 11325472
TI  - Characterization of monoclonal antibodies that specifically recognize the palm
      subdomain of hepatitis C virus nonstructural protein 5B polymerase.
AB  - The nonstructural protein 5B (NS5B) of hepatitis C virus (HCV) is an RNA
      dependent RNA polymerase (RdRp) which plays an essential role in viral RNA
      replication. Antibodies that specifically recognize NS5B will have utilities in
      monitoring NS5B production and subcellular localization, as well as in structure
      function studies. In this report, three mouse monoclonal antibodies (mAbs),
      16A9C9, 16D9A4 and 20A12C7, against a recombinant NS5B protein (genotype 1a, H-77
      strain) were produced. These mAbs specifically recognize HCV NS5B, but not RdRps
      of polivirus (PV), bovine viral diarrhea virus (BVDV) or GB virus B (GBV-B). The
      mAbs can readily detect NS5B in cellular lysates of human osteosarcoma Saos2
      cells constitutively expressing the nonstructural region of HCV (NS3-NS4A-NS4B
      NS5A-NS5B). NS5B proteins of different HCV genotypes/subtypes (1a, 1b, 2a, 2c,
      5a) showed varied affinity for these mAbs. Interestingly, the epitopes for the
      mAbs were mapped to the palm subdomain (amino acid 188-370) of the HCV RdRp as
      determined by immunoblotting analysis of a panel of HCV/GBV-B chimeric NS5B
      proteins. The binding site was mapped between amino acid 231 and 267 of NS5B for
      16A9C9, and between 282 and 372 for 16D9A4 and 20A12C7. Furthermore, these mAbs
      showed no inhibitory effect on the NS5B polymerase activity in vitro.

PMID- 11325474
TI  - Crystalline solids.
AB  - Many drugs exist in the crystalline solid state due to reasons of stability and
      ease of handling during the various stages of drug development. Crystalline
      solids can exist in the form of polymorphs, solvates or hydrates. Phase
      transitions such as polymorph interconversion, desolvation of solvate, formation
      of hydrate and conversion of crystalline to amorphous form may occur during
      various pharmaceutical processes, which may alter the dissolution rate and
      transport characteristics of the drug. Hence it is desirable to choose the most
      suitable and stable form of the drug in the initial stages of drug development.
      The current focus of research in the solid-state area is to understand the
      origins of polymorphism at the molecular level, and to predict and prepare the
      most stable polymorph of a drug. The recent advances in computational tools allow
      the prediction of possible polymorphs of the drug from its molecular structure.
      Sensitive analytical methods are being developed to understand the nature of
      polymorphism and to characterize the various crystalline forms of a drug in its
      dosage form. The aim of this review is to emphasize the recent advances made in
      the area of prediction and characterization of polymorphs and solvates, to
      address the current challenges faced by pharmaceutical scientists and to
      anticipate future developments.

PMID- 11325475
TI  - Amorphous pharmaceutical solids: preparation, characterization and stabilization.
AB  - The importance of amorphous pharmaceutical solids lies in their useful
      properties, common occurrence, and physicochemical instability relative to
      corresponding crystals. Some pharmaceuticals and excipients have a tendency to
      exist as amorphous solids, while others require deliberate prevention of
      crystallization to enter and remain in the amorphous state. Amorphous solids can
      be produced by common pharmaceutical processes, including melt quenching, freeze-
      and spray-drying, milling, wet granulation, and drying of solvated crystals. The
      characterization of amorphous solids reveals their structures, thermodynamic
      properties, and changes (crystallization and structural relaxation) in single-
      and multi-component systems. Current research in the stabilization of amorphous
      solids focuses on: (i) the stabilization of labile substances (e.g., proteins and
      peptides) during processing and storage using additives, (ii) the prevention of
      crystallization of the excipients that must remain amorphous for their intended
      functions, and (iii) the selection of appropriate storage conditions under which
      amorphous solids are stable.

PMID- 11325476
TI  - Characterization of the solid-state: spectroscopic techniques.
AB  - The physical characterization of pharmaceutical solids is an integral aspect of
      the drug development process. This review summarizes the use of solid-state
      spectroscopy techniques used in the physical characterization of the active
      pharmaceutical ingredient, excipients, physical mixtures, and the final dosage
      form. A brief introduction to infrared, Raman, and solid-state NMR experimental
      techniques are described as well as a more thorough description of qualitative
      and quantitative applications. The use of solid-state imaging techniques such as
      IR, Raman, and TOF-SIMS is also introduced to the reader.

PMID- 11325477
TI  - Characterization of the solid state: quantitative issues.
AB  - Quantitative analysis of solid state composition is often used to ensure the
      safety and efficacy of drug substances or to establish and validate the control
      of the pharmaceutical production process. There are a number of common techniques
      that can be applied to quantify the phase composition and numerous different
      methods for each technique. Each quantitative option presents its own issues in
      ensuring accuracy and precision of the solid state method. The following article
      describes many of the common techniques that are used for quantitative phase
      analysis and many of the considerations that are necessary for the development of
      such methods.

PMID- 11325478
TI  - Theoretical approaches to physical transformations of active pharmaceutical
      ingredients during manufacturing processes.
AB  - Processing-induced transformations (PITs) during pharmaceutical manufacturing are
      well known but difficult to predict and often difficult to control. This review
      of the concepts of transformations is couched in terms of the issues associated
      with identifying rate-controlling events from the materials side and the
      processing side. Specifically, the approach is reconciling the characteristic
      time scale of the structural change(s) in the material with the time scale of the
      processing-induced stress. This is definitely a model (or rather a melding of a
      group of existing theories) in development. This overview is a 'snapshot' of the
      authors' attempts to identify the categories of existing theories needed to
      encompass all of the relevant events for each possible PIT. The ultimate goal is
      to establish a framework of concepts and theories for consideration, discussion,
      and modeling of PITs as well as to locate much of the relevant literature in the
      framework.

PMID- 11325479
TI  - Chemical reactivity in solid-state pharmaceuticals: formulation implications.
AB  - Solid-state reactions that occur in drug substances and formulations include
      solid-state phase transformations, dehydration/desolvation, and chemical
      reactions. Chemical reactivity is the focus of this chapter. Of particular
      interest are cases where the drug-substance may be unstable or react with
      excipients in the formulation. Water absorption can enhance molecular mobility of
      solids and lead to solid-state reactivity. Mobility can be measured using various
      methods including glass transition (T(g)) measurements, solid-state NMR, and X
      ray crystallography. Solid-state reactions of drug substances can include
      oxidation, cyclization, hydrolysis, and deamidation. Oxidation studies of vitamin
      A, peptides (DL-Ala-DL-Met, N-formyl-Met-Leu-Phe methyl ester, and Met-enkaphalin
      acetate salt), and steroids (hydrocortisone and prednisolone derivatives) are
      discussed. Cyclization reactions of crystalline and amorphous angiotensin
      converting enzyme (ACE) inhibitors (spirapril hydrochloride, quinapril
      hydrochloride, and moexipril) are presented which investigate mobility and
      chemical reactivity. Examples of drug-excipient interactions, such as
      transacylation, the Maillard browning reaction, and acid base reactions are
      discussed for a variety of compounds including aspirin, fluoxitine, and
      ibuprofen. Once solid-state reactions are understood in a pharmaceutical system,
      the necessary steps can be taken to prevent reactivity and improve the stability
      of drug substances and products.

PMID- 11325480
TI  - Metabolic genetic polymorphisms and susceptibility to lung cancer.
AB  - Activity of some enzymes implicated in the metabolism of tobacco carcinogens
      presents a great variability between individuals due to the existence of a
      polymorphism in gene coding for these enzymes. Individual susceptibility to
      develop lung cancer could therefore depend not only on exposure to tobacco
      smoking, but also on genetic capacity to activate or inactivate tobacco
      carcinogens. This article summarizes the state of knowledge on metabolic
      polymorphisms and lung cancer susceptibility, and opens the discussion on the
      future direction of this promising way of research.

PMID- 11325481
TI  - Asbestos fiber burdens in lung tissues of Hong Kong Chinese with and without lung
      cancer.
AB  - To investigate the asbestos exposure level in non-occupational population and its
      relation to lung cancer, pulmonary asbestos fiber counts were observed with a
      modified alkali digestion method, in lung tissues from 65 random surgically
      treated lung cancer patients (42 males and 23 females) and that obtained from 107
      random autopsy cases who died of either accidental death or acute myocardial
      infarction (44 males and 63 females) during 1987-1988. The patients and cases
      were all Hong Kong Chinese with no definite history of occupational exposure to
      asbestos. The non-lung cancer cases (NLCC) were divided into three groups based
      on different age ranges: 10 approximately, 40 approximately and 70 approximately
      years. The results showed that the medians of uncoated fiber counts (0, 32 and 52
      fibers per mg dry tissue [f/mgDT] in the different age groups, respectively)
      increased in an age-dependent manner (P<0.01). However, the medians of coated
      fiber (asbestos body) counts were all 0 f/mgDT, with no statistically significant
      difference among the groups, showing a very low level of asbestos body burden in
      NLCC. In each age group, no difference in those counts between males and females
      was observed (P>0.05). Moreover, those counts in male lung cancer cases (medians
      of 62.5 and 17.5 f/mgDT, respectively) were greater than that in the control
      (32.5 and 0 f/mgDT, respectively) (P<0.01, P<0.05, respectively), however,
      regarding the female groups there was no statistically significant difference
      from the control. The results suggest that there is an environmental exposure to
      asbestos in Hong Kong Chinese, the level of which is, however, generally not
      sufficient to induce asbestos body. Environmental asbestos exposure in Hong Kong
      males may be one of the carcinogenic factors leading to lung cancer.

PMID- 11325482
TI  - Topoisomerase IIalpha and other drug resistance markers in advanced non-small
      cell lung cancer.
AB  - Resistance to chemotherapy is common in non-small cell lung cancer. The aim of
      this study was to investigate the prognostic impact of in vitro established drug
      resistance markers on the response to chemotherapy in patients with advanced non
      small cell lung cancer. Samples of 38 patients were analyzed by
      immunohistochemical staining, for topoisomerase IIalpha and IIbeta, Ki-67, MRP
      and LRP. In addition, mutation analysis of the topoisomerase IIalpha gene, the
      B/DNBS and the Tyr804 region, was performed. Lung tumor biopsies were taken prior
      for treatment with one of the following regimens; cisplatin/paclitaxel,
      cisplatin/VM26 or VP16, or carboplatin/VP16/ifosfamide. Seventeen patients
      obtained a partial response, 12 had stable disease and nine patients had
      progressive disease. None of the investigated markers was related with overall
      response rate. In one sample a point mutation in the B/DNBS region of the topo
      IIalpha gene was detected which substitutes IIe(510) with Val. This tumor had a
      partial response to four courses of cisplatin/VP16 treatment. The survival
      analysis showed that the patients with high topo IIalpha expressing tumors had a
      significantly worse survival compared with the patients with low or intermediate
      topo IIalpha expressing tumors. In conclusion, no relation was observed between
      expression of topoisomerase IIalpha, IIbeta, Ki-67, MRP or LRP and response rate.
      Furthermore, worse survival was seen in patients with high topoisomerase IIalpha
      expressing tumors. In one tumor sample, a newly described mutation in the B/DNBS
      region of the topo IIalpha gene was detected, which does not appear to be related
      to drug resistance.

PMID- 11325483
TI  - Brain metastases and non-small cell lung cancer. Prognostic factors and
      correlation with survival after irradiation.
AB  - A total of 250 patients with brain metastases from non-small cell lung cancer
      (NSCLC) were treated with irradiation of their brain metastases. The median
      overall survival was 3.1 (95% CI: 2.7-3.5) months. 32/250 patients presenting
      with solitary brain metastasis underwent surgical resection. Their 1-year
      survival rate of 58% was significantly better than 89/250 patients with a
      solitary lesion but without surgery (14%, P=0.001). Patients with an absent or
      controlled primary tumor (101/250, 40.5%) had a 1-year survival rate of 26% as
      opposed to 11% for patients presenting with an active primary tumor (P=0.051).
      Patients presenting with metastases to the brain only showed a significant
      survival advantage over patients with extracranial metastases (1-year survival of
      21% vs 6%, P=0.001). Karnofsky performance score, neurofunction status and
      response to steroids were also identified as prognostic factors. The total dose
      whole brain irradiation (WBI) was prognostic of significance with a 1-year
      survival of 35% for 30 Gy and boost, 23.5% for 30 Gy and 4% for the patients
      irradiated to a dose of 20 Gy WBI (P=0.001). When patients were grouped into the
      RTOG RPA (Recursive partitioning analysis) classes, patients within class I
      (73/250) had a 1-year survival of 28.5%, patients in class II (145/250) a
      survival of 14% at 1 year and patients into class III only a 6% 1-year survival
      rate. In a multivariate analysis, surgical resection, neurofunction class,
      metastatic extent and WBI dose remained significant prognostic factors. Although
      survival remains poor, there needs to be a continued interest in these patients,
      probably by participating in clinical trials.

PMID- 11325484
TI  - Diagnostic and prognostic significance of squamous cell carcinoma antigen in non
      small cell lung cancer.
AB  - Squamous cell carcinoma antigen (SCC-Ag) is a glycoprotein secreted by non-small
      cell lung tumours (NSCLC). This study investigated the diagnostic and prognostic
      significance of SCC-Ag in NSCLC. Receiver operating characteristic (ROC) curve
      analysis was used to test the diagnostic performance of the SCC-Ag and determine
      the optimal threshold value in a group of 100 NSCLC patients undergoing surgery
      and 50 age matched healthy controls. This threshold was then prospectively
      validated in a group of 53 patients and 49 healthy controls. The prognostic
      significance of the preoperative SCC-Ag level and its postoperative decrease were
      tested using univariate and multivariate proportional hazard models. The area
      under the ROC curve was 0.71+/-0.04, and the best cutoff value was 1.4 ng/ml.
      This discriminated patients in the validation group, with a sensitivity of 0.55
      and a specificity of 1.0. The hazard ratio was 0.144 (95% CI 0.074-0.281) for the
      postoperative decrease in the SCC Ag, and 5.823 (3.299-10.278) for the
      preoperative SCC Ag level. Multivariate analysis revealed that only disease stage
      and patients' age are strong prognostic factors for survival. In conclusion, the
      SCC-Ag serum level has moderate diagnostic role in NSCLC. Both the preoperative
      SCC-Ag level and its postoperative decrease have prognostic significance, yet
      inferior to the disease stage and the patient's age.

PMID- 11325485
TI  - An evaluation of two techniques for beam intensity modulation in patients
      irradiated for stage III non-small cell lung cancer.
AB  - In locally advanced lung cancer, the use of high dose radiotherapy (RT) and/or
      concurrent chemo-RT is associated with significant pulmonary and esophageal
      toxicity. Despite a 3D conformal RT technique and the omission of elective
      mediastinal fields, three (of ten) patients with inoperable stage 3 NSCLC who
      were treated with induction chemotherapy (carboplatin-paclitaxel) followed by RT
      to 70 Gy, developed symptomatic radiation pneumonitis. In this planning study,
      the actual treatment plans of all ten patients were compared to plans derived
      using two beam intensity-modulated (BIM) techniques, for which similar
      geometrical beam setup parameters were used. In the first technique (BF-BIM),
      cranial and caudal boost fields were applied in order to allow field length
      reduction. The second technique (C-BIM) utilised 3-D missing-tissue compensators
      for all radiation beams. Both BIM techniques resulted in a significant sparing of
      critical normal tissues and the C-BIM technique was superior in all cases. When
      compared to the actual RT technique used for treatment, a reduction of 8.1+/-4.7%
      (1 S.D.) was observed in the mean lung dose for the BF-BIM plan, vs. 20.3+/-5.8%
      (1 S.D.) for the C-BIM plan. Similar reductions were observed in the percentage
      of the total lung volume exceeding 20 Gy (V(20)) for these techniques. BIM
      techniques appear to be a promising tool for enabling radiation dose-escalation
      and/or intensive concurrent chemo-RT in inoperable lung cancer.

PMID- 11325486
TI  - Paclitaxel added to the cisplatin/etoposide regimen in extensive-stage small cell
      lung cancer -- the use of complete response rate as the primary endpoint in phase
      II trials.
AB  - Obtaining a complete response (CR) is the most powerful predictor of survival in
      extensive-stage small cell lung cancer (SCLC). Improvements in long-term survival
      in extensive-stage SCLC can be made if the proportion of complete responders to
      induction therapy can be increased. We performed a phase II trial of the
      feasibility of adding paclitaxel to standard cisplatin/etoposide (EP regimen) in
      extensive-stage SCLC. The primary endpoint for this trial is the proportion of
      patients (pts) obtaining a CR rather than overall response. The null hypothesis
      for this trial consists of the absence of a CR rate >20%. Paclitaxel was given at
      doses of 135 (3 pts) or 170 mg/m(2) i.v. over 3 h on day 1. Cisplatin 60 mg/m(2)
      was given on day 1. On days 1-3 etoposide 80 mg/m(2) per day i.v. was given. G
      CSF was used from days 5 to 14 of each cycle. Cycles were repeated q21 days. A
      two-stage design was used for patient accrual, based on the occurrence of
      complete responses. Initially, 16 patients were to be accrued. If more than three
      complete responses were to occur, a further 20 patients would be accrued to the
      study (Simon's optimal two stage design). Sixteen patients were enrolled. Two
      patients had a CR (13%) and nine patients had a partial response (56%) for an
      overall response rate of 69%. The trial was suspended due to the low CR rate.
      Review of the literature for paclitaxel based front-line treatment combined with
      EP therapy, in extensive stage SCLC, consistently shows a CR rate <20% but high
      overall response rate is maintained (thus most responses are partial). As
      virtually all long-term survivors in extensive-disease SCLC have had a CR to
      induction therapy and CR remains the strongest predictor of survival for this
      disease, this may suggest that paclitaxel added to standard EP may improve
      progression-free survival (and possibly median survival) but is unlikely to
      significantly improve long-term survival. Initial randomized phase III data
      confirm the absence of impact on survival for this triple-drug regimen compared
      to EP therapy alone. Furthermore, other regimens comparing favorably to the EP
      regimen have all shown consistent CR rates >20% in the phase II setting. In
      conclusion, consideration should be given to the use of CR rate as a phase II
      endpoint to determine if a particular regimen should be compared to the standard
      in a phase III setting for extensive-stage SCLC. A two-stage phase II design
      based on a minimum required completed responses for further patient accrual is
      recommended.

PMID- 11325487
TI  - Sequential chemo- and radiochemotherapy with weekly paclitaxel (Taxol) and 3D
      conformal radiotherapy of stage III inoperable non-small cell lung cancer.
      Results of a dose escalation study.
AB  - The purpose of this study was the determination of the maximum tolerable dose
      (MTD) of weekly paclitaxel (PX) in combination with 3D-conformal radiotherapy in
      non-small cell lung cancer (NSCLC) and the evaluation of side effects, patient
      outcome and tumor response. Thirty-eight patients with inoperable NSCLC, UICC
      stage IIIA (n=14)/IIIB (n=24) received two cycles of induction chemotherapy with
      PX/carboplatin followed by combined radiochemotherapy (60 Gy/6 weeks) with weekly
      PX which was escalated in cohorts of four patients until dose limiting toxicity
      (DLT) was reached. Starting level was 40 mg/m(2). 3D-conformal radiotherapy was
      applied in all patients. Toxicity was determined by WHO criteria. Patients were
      followed-up 3-monthly. Thirty eight patients have entered the study, 34 patients
      are evaluable. DLT was esophagitis III degrees, requiring interruption of
      radiotherapy and was reached at the PX 70 mg/m(2). Two hypersensitivity reactions
      (50 mg/m(2)) and one leucopenia III degrees (60 mg/m(2)) were observed. Only one
      patient (60 mg/m(2), 50 Gy) completely aborted treatment. The pneumonitis rate
      was between 21 and 36% but showed no clear correlation with PX dose. Tumor
      response (PR and CR) defined by CT-scan 6 weeks following radiotherapy was 88%
      (30/34). The 1- and 2-year survival rate is 73% and 34%. We conclude that the MTD
      of weekly PX with 60 Gy normofractionated radiotherapy is 60 mg/m(2). The DLT is
      esophagitis. Response and survival data of this sequential/combined approach are
      promising. A minor increase of pulmonary toxicity of irradiation is suspected.

PMID- 11325488
TI  - Carboplatin and vinorelbine in untreated locally advanced and metastatic non
      small cell lung cancer.
AB  - The aim of this study was to assess the activity and toxicity of
      carboplatin/vinorelbine combination chemotherapy in unresectable locally advanced
      and metastatic non-small cell lung cancer. Between April 1997 and June 1999 30
      patients (22 M, eight F, median age 62) received treatment with carboplatin AUC 6
      on day 1, and vinorelbine 25mg/m(2) on days 1, 8 and 15. Treatment was given
      every 28 days for six cycles unless progressive disease occurred. Twenty-three
      patients (77%) had stage IV disease, and seven (23%) stage IIIB. Ninety-three
      percent were WHO performance status 0-1. Twenty-three patients were fully
      assessable. Nine patients achieved partial responses (9/23, 39%) for an overall
      objective response rate of 9/30 (30%; 95% CI 15-49%). The median duration of
      response was 2.75 months (range 1-13 months). The median progression-free
      survival was 2 months and the median survival 5.25 months. The actuarial 1-year
      survival was 20%. The median number of cycles completed was two (range 1-6). Day
      15 vinorelbine was administered in only 18% of cycles. The main toxicity was
      myelosuppression. WHO grade III/IV neutropenia was experienced in 50% of
      patients, however, there were only three episodes of febrile neutropenia. Eight
      patients required blood transfusion and one developed grade III thrombocytopenia.
      Treatment was ceased in one patient because of grade IV autonomic neuropathy. No
      patient had significant nausea and vomiting. There were no treatment-related
      deaths. These results indicate that carboplatin/vinorelbine is well tolerated and
      has similar activity to cisplatin/vinorelbine in patients with unresectable non
      small cell lung cancer, however, the median survival was considerably shorter.

PMID- 11325490
TI  - Phase I study of gemcitabine and carboplatin in advanced non-small cell lung
      carcinoma.
AB  - BACKGROUND: This phase I study was designed to determine the maximum tolerated
      dose of carboplatin with a fixed dose of gemcitabine without growth factor or
      hematopoietic precursor support. METHODS: Nineteen patients with previously
      untreated non-small cell lung cancer (NSCLC) were treated at three dose levels.
      Initially, the gemcitabine dose was 1000 mg/m(2) given on days 1 and 8. Of the
      first five patients treated with carboplatin AUC 4, three experienced dose
      limiting toxicity (DLT). The study was, therefore, amended to decrease the dose
      of gemcitabine to 800 mg/m(2) given on days 1 and 8 in a 21-day cycle. RESULTS:
      Dose limiting toxicity (neutropenia and thrombocytopenia) were seen at dose level
      2A (carboplatin AUC=5). Thus, no further dose escalation was performed. Grade 3
      and 4 toxicities were seen as follows: leukopenia in five of 18 (28%);
      neutropenia, four of 18 (22%); and thrombocytopenia, four of 18 (22%) evaluable
      patients. Grade 3 or 4 anemia occurred in one of 18 (6%) patients and no
      neutropenic fever or treatment related mortality was observed. Partial responses
      were seen in six patients and one patient with evaluable disease had an objective
      response. The overall response rate was 37% (seven of 19). Six other patients had
      stable disease. A total of 89 courses were administered with a median of five
      courses per patient (range: two to six courses). The median time to progression
      for all patients was 3.7 months. The median overall survival was 7.4 months with
      four patients still alive (median follow up 13.5 months). The survival at 6
      months and 1 year is 64 and 23%, respectively. CONCLUSION: The maximum tolerated
      dose (MTD) in this group of patients was defined as carboplatin AUC 4 when
      administered with gemcitabine 800 mg/m(2) on days 1 and 8 of a 21-day schedule.

PMID- 11325489
TI  - Docetaxel in combination with gemcitabine plus rhG-CSF support as second-line
      treatment in non-small cell lung cancer. A multicenter phase II study.
AB  - BACKGROUND: Docetaxel in combination with gemcitabine is an active front-line
      chemotherapy regimen against non-small cell lung cancer (NSCLC) with acceptable
      toxicity. A multicenter phase II study was conducted in order to determine the
      toxicity and efficacy of this combination, as salvage treatment in patients
      progressing after a cisplatin-based front line regimens. PATIENTS AND METHODS:
      Thirty-two patients with histologically confirmed, bidimensionally measurable
      NSCLC, who failed prior cisplatin-based chemotherapy were enrolled. The patients'
      median age was 62.5 years, 29 (91%) were male, 23 (72%) had disease stage IV, and
      22 (69%) had a performance status (WHO) 0-1. Gemcitabine (900 mg/m(2)) was
      administered on days 1 and 8 and docetaxel (100 mg/m(2)) on day 8, after
      appropriate premedication. rhG-CSF (150 microg/m(2)) was given prophylactically
      from day 9 to 15. Treatment was repeated on an outpatient basis every three
      weeks. RESULTS: A total of 127 chemotherapy cycles were administered. In an
      intention-to-treat analysis five patients (15.6%; 95% CI: 3.04-28.21%) achieved a
      partial response, 11 (34.4%) stable disease, and 16 (50%) progressive disease.
      The median duration of response was 9 months, the median TTP 7 months, and the
      overall median survival 6.5 months; the overall 1-year survival probability was
      27.6%. Grade 3/4 neutropenia was observed in five (15.6%) patients and in two of
      them associated with fever. Grade 3 anemia and thrombocytopenia occurred in three
      (9%) and two (6.5%) patients, respectively. Non-hematologic toxicity was very
      mild with only one episode of grade 4 diarrhea and mucositis, respectively; two
      (6%) patients complained for grade 3 asthenia. CONCLUSION: The combination of
      gemcitabine and docetaxel with prophylactic use of rhG-CSF is a safe and well
      tolerated regimen for the treatment of patients with advanced NSCLC, who failed
      front-line treatment with cisplatin-based regimens.

PMID- 11325491
TI  - Localised spontaneous regression in mesothelioma -- possible immunological
      mechanism.
AB  - Malignant mesothelioma (MM) is an aggressive tumor usually associated with
      asbestos exposure. Although it can remain stable for prolonged periods, it has
      not been described to spontaneously regress. MM tumors are thought to be
      immunogenic based both on animal studies and on the good responses in some humans
      treated with immunotherapy. Here we present a case of pleural MM in which a
      transient spontaneous regression was associated with tumor tissue infiltration
      with mononuclear cells and serological evidence of anti-MM reactivity. The
      patient's tumor eventually progressed and with this progression there was
      evidence of loss of serological reactivity to some, but not all, of her MM
      antigens. The patient survived for 20 months and, in contrast to her initial
      biopsy, no significant lymphoid infiltrate was detected in her MM tissue at post
      mortem examination.

PMID- 11325492
TI  - A left pleural effusion with a calcified tumoral mass and left hemithoracic
      uptake on bone scan.
AB  - Diffuse malignant pleural mesothelioma is a rare primary tumor of the pleura with
      three principal histological types, epithelial; mesenchymal and mixed epithelial
      and mesenchymal. We report here a case of a mesenchymal mesothelioma with foci of
      osteosarcomatous degeneration revealed by dense calcifications associated with
      the pleural effusion on the computed tomography (CT) of the thorax. The bone scan
      revealed extraosseous uptake corresponding to the left pleura.

PMID- 11325494
TI  - Extramedullary plasmacytoma of the breast simulating breast cancer.
AB  - A patient with a palpable mass in the breast suggestive of carcinoma underwent
      radical modified mastectomy. Surprisingly, histology of the tumor revealed an
      extramedullary plasmacytoma. Further diagnostic work up showed no evidence of
      underlying multiple myeloma. Among neoplastic lesions of the breast, although
      rare, malignancy of mesenchymal or lymphoproliferative origin should always be
      considered.

PMID- 11325493
TI  - What happens to patients starting dialysis in the Netherlands?
AB  - BACKGROUND: despite improvements in dialysis technology, publications around 1990
      showed increasing mortality rates in dialysis patients. The Dialysis Group of the
      Netherlands initiated the Netherlands Cooperative Study on the Adequacy of
      Dialysis (NECOSAD) to investigate the association of patient and therapy
      characteristics with outcome. METHODS: 250 patients were included in this
      prospective multicentre study 3 months after the start of dialysis. We used Cox
      regression to predict mortality and technique failure and repeated measures
      analysis of variance to study the time course of continuous parameters. RESULTS:
      there were considerable differences in patient populations among dialysis
      centres. Patient survival was 76% at 2 years. Technique survival was higher in
      haemodialysis. Hospitalisation decreased from 25 days between 3 and 12 months to
      19 days per patient year in the third year. Residual renal function decreased at
      a similar rate in both modalities, but blood pressure tended to increase in
      females receiving peritoneal dialysis. Outcome was predominantly dependent on
      patient characteristics. CONCLUSIONS: In the light of the increasing age of
      patients starting dialysis, increasing mortality can be expected. Furthermore, if
      outcome is to play a role in the quality assessment of dialysis centres, it is
      essential to know the characteristics of their patient populations.

PMID- 11325495
TI  - A 49-year-old woman with well-differentiated fetal adenocarcinoma.
AB  - A 49-year-old woman underwent a pneumonectomy because of a mass in the middle
      lobe. Histological examination of the tumour showed a well-differentiated fetal
      adenocarcinoma (WDFA). This rare tumour appears to be associated with an
      excellent prognosis in the absence of metastases following surgical resection.

PMID- 11325496
TI  - Regression of invasive thymoma following corticosteroid therapy.
AB  - A case of invasive thymoma is presented showing tumour regression after
      palliative treatment with prednisone. Moderate doses of prednisone resulted in a
      longtime palliation via remarkable anti-tumour effect. The literature of
      corticosteroid responses of thymomas is reviewed.

PMID- 11325497
TI  - Atypical carcinoid presenting as mesothelioma.
AB  - Two patients presented with pleuritic pain and dyspnoe together with pleural
      thickening on the X-ray of the chest. In both a history of exposure to asbestos
      existed suggesting mesothelioma. A definite diagnosis could not be made and
      therefore therapy was symptomatic. Autopsy revealed the unexpected diagnosis of
      atypical carcinoid of the lung. In one case, pleural spread of tumor was seen
      while in the other an extensive fibrotic pleural reaction existed. To our
      knowledge these cases represent the first examples of atypical carcinoid causing
      pseudomesothelioma.

PMID- 11325499
TI  - The physics and evolution of symbols and codes: reflections on the work of Howard
      Pattee.

PMID- 11325500
TI  - The physics of symbols: bridging the epistemic cut.
AB  - Evolution requires the genotype-phenotype distinction, a primeval epistemic cut
      that separates energy-degenerate, rate-independent genetic symbols from the rate
      dependent dynamics of construction that they control. This symbol-matter or
      subject-object distinction occurs at all higher levels where symbols are related
      to a referent by an arbitrary code. The converse of control is measurement in
      which a rate-dependent dynamical state is coded into quiescent symbols. Non
      integrable constraints are one necessary condition for bridging the epistemic cut
      by measurement, control, and coding. Additional properties of heteropolymer
      constraints are necessary for biological evolution.

PMID- 11325501
TI  - Unity of measurement and motion.
AB  - Issues addressed in H.H. Pattee's origin of life laboratory in the 1960s and
      their connection to the physics-evolution-language problematic are indicated. The
      problem of quantum measurement played a central role. The problem is herein
      examined in the light of the fluctuon model; in particular, as the model applies
      to gravity. The main conclusion is that measurement and motion are a unitary
      process. All accelerations are accompanied by a cycle involving the annihilation
      and creation of superpositions. Gravitational collapse is also a cyclic process
      in the fluctuon model. By a suitable transformation, it can be seen that
      interactions underlying superpositional collapse are the same as those operative
      in gravitational collapse. Implications for the origin of cellular life and the
      development of symbolic systems are considered.

PMID- 11325502
TI  - Self-description and the origin of the genetic code.
AB  - The genetic code presents an important conceptual challenge within the broader
      context of the origin of life. Translation of genetic information captures a
      fundamental property of living systems, i.e. the ability of decoding proteins
      (e.g. aminoacyl-tRNA synthetases) to reproduce themselves from self-contained
      RNA/DNA descriptors. Silvano Colombano and I, as graduate students with Howard
      Pattee in the 1970s, focused on achieving this closure of self-description and
      self-reproduction in the genetic code. Simulation and analysis of competitive
      models that allowed alternate code assignments, exploring initial conditions,
      arbitrary descriptor-catalyst relationships, and degree of non-linearity,
      indicated that these dynamical systems undergo bifurcations, transforming initial
      ambiguous stable states to unstable states. New, stable, steady states,
      progressively closer to a code, became available as the descriptor parameters
      were varied. The efficiency of utilization of raw materials for the production of
      a coding family of catalysts is proposed as a selection criterion that drives
      such systems towards a coded state.

PMID- 11325503
TI  - Autocatalysis, information and coding.
AB  - Autocatalytic self-construction in macromolecular systems requires the existence
      of a reflexive relationship between structural components and the functional
      operations they perform to synthesise themselves. The possibility of reflexivity
      depends on formal, semiotic features of the catalytic structure-function
      relationship, that is, the embedding of catalytic functions in the space of
      polymeric structures. Reflexivity is a semiotic property of some genetic
      sequences. Such sequences may serve as the basis for the evolution of coding as a
      result of autocatalytic self-organisation in a population of assignment
      catalysts. Autocatalytic selection is a mechanism whereby matter becomes
      differentiated in primitive biochemical systems. In the case of coding self
      organisation, it corresponds to the creation of symbolic information. Prions are
      present-day entities whose replication through autocatalysis reflects aspects of
      biological semiotics less obvious than genetic coding.

PMID- 11325504
TI  - Symbols and dynamics in the brain.
AB  - The work of physicist and theoretical biologist Howard Pattee has focused on the
      roles that symbols and dynamics play in biological systems. Symbols, as discrete
      functional switching-states, are seen at the heart of all biological systems in
      the form of genetic codes, and at the core of all neural systems in the form of
      informational mechanisms that switch behavior. They also appear in one form or
      another in all epistemic systems, from informational processes embedded in
      primitive organisms to individual human beings to public scientific models. Over
      its course, Pattee's work has explored (1) the physical basis of informational
      functions (dynamical vs. rule-based descriptions, switching mechanisms, memory,
      symbols), (2) the functional organization of the observer (measurement,
      computation), (3) the means by which information can be embedded in biological
      organisms for purposes of self-construction and representation (as codes,
      modeling relations, memory, symbols), and (4) the processes by which new
      structures and functions can emerge over time. We discuss how these concepts can
      be applied to a high-level understanding of the brain. Biological organisms
      constantly reproduce themselves as well as their relations with their environs.
      The brain similarly can be seen as a self-producing, self-regenerating neural
      signaling system and as an adaptive informational system that interacts with its
      surrounds in order to steer behavior.

PMID- 11325505
TI  - The role of computation in modeling evolution.
AB  - Artificial life uses computers and formal systems to model and explore the
      dynamics of evolution. A fundamental question for A-Life concerns the role of
      computation in these models, and how we are to interpret computer implementations
      that do not have actual contact with physical systems. In this paper I will
      discuss how models are seen to explain and predict in philosophy of science and
      how these ideas apply to A-Life. I will also explore how the notion of an
      epistemic cut, as defined by H. Pattee, can be realized in a computational model
      with an artificial physical world.

PMID- 11325506
TI  - Evolution with material symbol systems.
AB  - Pattee's semantic closure principle is used to study the characteristics and
      requirements of evolving material symbols systems. By contrasting agents that
      reproduce via genetic variation with agents that reproduce via self-inspection,
      we reach the conclusion that symbols are necessary to attain open-ended
      evolution, but only if the phenotypes of agents are the result of a material,
      self-organization process. This way, a study of the inter-dependencies of symbol
      and matter is presented. This study is based first on a theoretical treatment of
      symbolic representations, and secondly on simulations of simple agents with
      matter-symbol inter-dependencies. The agent-based simulations use evolutionary
      algorithms with indirectly encoded phenotypes. The indirect encoding is based on
      Fuzzy Development programs, which are procedures for combining fuzzy sets in such
      a way as to model self-organizing development processes.

PMID- 11325507
TI  - Life and reference.
AB  - The paper recommends a broadening of Howard Pattee's seminal distinction between
      a dynamic and a linguistic mode of living systems. It is observed that even the
      dynamic mode is always a semiotic mode although indexical and analogically coded
      rather than symbolic and digitally coded. The analogically coded messages
      corresponds to a kind of tacit knowledge hidden in macromolecular structure and
      shape (e.g. molecular complementarity) and in organismic architecture and
      communication, i.e. in the semiotic interactions of the body. It is claimed that
      the origin of referential processes is tied to the flow of historical
      singularities. The function of analog and digital codes in evolutionary systems
      is discussed.

PMID- 11325508
TI  - The semiotics of control and modeling relations in complex systems.
AB  - We provide a conceptual analysis of ideas and principles from the systems theory
      discourse which underlie Pattee's semantic or semiotic closure, which is itself
      foundational for a school of theoretical biology derived from systems theory and
      cybernetics, and is now being related to biological semiotics and explicated in
      the relational biological school of Rashevsky and Rosen. Atomic control systems
      and models are described as the canonical forms of semiotic organization, sharing
      measurement relations, but differing topologically in that control systems are
      circularly and models linearly related to their environments. Computation in
      control systems is introduced, motivating hierarchical decomposition, hybrid
      modeling and control systems, and anticipatory or model-based control. The
      semiotic relations in complex control systems are described in terms of
      relational constraints, and rules and laws are distinguished as contingent and
      necessary functional entailments, respectively. Finally, selection as a meta
      level of constraint is introduced as the necessary condition for semantic
      relations in control systems and models.

PMID- 11325509
TI  - From complexity to simplicity: nature and symbols.
AB  - This paper reviews Pattee's ideas about the symbolic domain as a phenomenon
      related to the self-simplifying processes of certain hierarchical systems, such
      as the living. We distinguish the concepts of constraint, record, and symbol to
      explain how the Semantic Closure Principle, that is to say, the view that symbols
      are self-interpreted by the cell, emerges. Related to this, the notion of
      complementarity is discussed both as an epistemological and as an ontological
      principle. In the final discussion we consider whether autonomous systems can
      exist in which constraints are not symbolically preserved, and if biological
      symbols can be considered to have a descriptive nature.

PMID- 11325510
TI  - Howard Pattee's theoretical biology--a radical epistemological stance to approach
      life, evolution and complexity.
AB  - This paper offers a short review of Pattee's main contributions to science and
      philosophy. With no intention of being exhaustive, an account of Pattee's work is
      presented which discusses some of his ideas and their reception. This is done
      through an analysis centered in what is thought to be his main contribution: the
      elaboration of an internal epistemic stance to better understand life, evolution
      and complexity. Having introduced this core idea as a sort of a posteriori
      cohesive element of a complex but highly coherent and complete system of
      thinking, further specific elements are also reviewed.

PMID- 11325511
TI  - Hydroxysteroid dehydrogenases: ancient and modern regulators of adrenal and sex
      steroid action.
AB  - The adrenal and sex steroids receptor clade arose from an ancestral nuclear
      receptor in a primitive vertebrate at least 540 million years ago during the
      early Cambrian. At that time, these receptors had less specificity for their
      canonical ligands than their descendents in mammals have, which raises the
      question of how specificity for responses to different steroids was regulated. We
      propose that hydroxysteroid dehydrogenases that metabolized functional groups at
      different sites on steroids (e.g. C3, C11, C17 and C20) had a key role in
      providing specificity for steroid regulation of gene transcription in primitive
      vertebrates. Later, with increased physiological complexity in land animals due
      to innovations such as the placenta, hydroxysteroid dehydrogenases were recruited
      for new roles in regulating steroid-mediated physiological responses.
      Hydroxysteroid dehydrogenases in fish, amphibia and mammals are likely have
      different affinities for some xenobiotics, which needs to be considered in
      evaluating their hazards as endocrine disruptors.

PMID- 11325512
TI  - CCK expression in enteroendocrine cell is regulated by soluble factor(s) from
      underlying fibroblasts.
AB  - Studies on the cross-talk between the intestinal epithelium and the underlying
      connective tissue have concentrated on enterocytes. In contrast, little is known
      about the interactions between the mesenchymal compartment and the
      enteroendocrine cells, scattered among the other cell types of the epithelium. To
      address this question, a panel of coculture systems between the enteroendocrine
      STC-1 cell line and three intestinal myofibroblastic cell lines (MIC) was used in
      order to assess different levels of regulation, namely cell-cell and cell-matrix
      interactions, and the role of diffusible factors. We demonstrate that the
      expression of cholecystokinin, a typical intestinal hormone produced by STC-1
      cells, is up-regulated in the presence of a fibroblastic environment through a
      paracrine pathway involving FGF2. Concomitantly, STC-1 cell morphology and
      proliferation were also modulated, but through distinct mechanisms according to
      the origin of fibroblasts. The results reveal definite epithelio-mesenchymal
      interactions that may be critical for the maintenance of phenotype and function
      of enteroendocrine cells.

PMID- 11325513
TI  - The IGFBP-3 mRNA and protein levels are IGF-I-dependent and GH-independent in MG
      63 human osteosarcoma cells.
AB  - Growth Hormone (GH), Insulin-like Growth Factors (IGFs) and IGF-Binding Proteins
      which modulate the IGFs' bioavailability (e.g. IGFBP-3, -4, -5), are essential
      regulators of bone remodeling. In this study, MG-63 human osteosarcoma cells were
      used as a model system to investigate the mechanism(s) whereby IGF-I and GH
      control IGFBP-3 gene expression. Physiological concentrations of IGF-I (1-20 nM)
      induced a dose-dependent increase in the steady-state amount of IGFBP-3 mRNA
      (maximal stimulation: approximately 9-10-fold). This increase was detectable 3 h
      after the onset of IGF-I treatment, was enhanced over a 24 h period, then
      plateaued until at least 30 h. Consistently, a dose-dependent increase in IGFBP-3
      secretion ( approximately 40-50-fold at IGF-I concentrations>/=16 nM) was
      observed by western ligand- and immuno-blot analysis of MG-63 cells conditioned
      medium, and its time course was similar to that observed for IGFBP-3 transcripts.
      IGFBP-3 mRNA stability (t(1/2) approximately 20 h) was identical in the presence
      or absence of IGF-I treatment. By contrast, human (h) GH treatment (24-72 h) of
      MG-63 cells did not increase IGFBP-3 secretion in the conditioned medium. Ectopic
      expression of recombinant rat GH-R resulted in hGH-enhanced expression of GH
      responsive reporter gene constructs, but did not increase endogenous IGFBP-3 gene
      expression, suggesting that the GH unresponsiveness was not only due to the very
      low level of GH binding sites at the plasma membrane level. Altogether, these
      results support the conclusions that in MG-63 cells (i) transcriptional rather
      post-transcriptional mechanisms are involved in the IGF-I-induced increase of
      IGFBP-3; (ii) the abundance of GH-R is very low at the plasma membrane level;
      (iii) the dowstream GH-signaling cascade is fully functional in this human
      osteosarcoma cell line; and (iv) the endogenous IGFBP-3 gene is not responsive to
      hGH in human MG-63 osteosarcoma cells.

PMID- 11325514
TI  - Stromal-epithelial interactions in the progression of ovarian cancer: influence
      and source of tumor stromal cells.
AB  - Stromal cells are essential for the progression of many cancers including ovarian
      tumors. Stromal cell-epithelial cell interactions are important for tumor
      development, growth, angiogenesis, and metastasis. In the current study, the
      effects of normal ovarian bovine stromal cells on ovarian tumor progression was
      investigated. The hypothesis tested is that ovarian stromal cells will alter the
      onset and progression of ovarian tumors. Conditioned medium from normal bovine
      ovarian surface stromal cells was found to stimulate the growth of normal ovarian
      surface epithelium and had no effect on the growth of human tumor cell lines
      SKOV3 and OCC1. Human ovarian cancer cell lines, SKOV3 and OCC1, were injected
      subcutaneously into nude mice to examine tumor progression. Tumor growth in the
      nude mice was dramatically reduced when normal ovarian surface stromal cells were
      co-injected with SKOV3 or OCC1 cells. Similar results were obtained with normal
      bovine or human ovarian stromal cells. In contrast, irrelevant testicular stromal
      cells and epithelial cells had no effect on tumor growth in the nude mouse.
      Histological examination of these tumors revealed a characteristic stromal cell
      component adjacent to epithelial cell colonies. Sections of these tumors were
      hybridized with species specific genomic probes using fluorescence in situ
      hybridization to identify cell populations. Epithelial cells were shown to be of
      human origin (i.e. SKOV3 or OCC1), but stromal cells were found to be primarily
      murine in origin (i.e. host tissue). No detectable bovine cells were observed in
      the tumors after one week post-injection. Results suggest that stromal cells are
      an essential component of ovarian tumors. Interestingly, normal ovarian stromal
      cells had the ability to inhibit tumor growth, but were not able to survive long
      term incubation at the tumor site. The developing tumor appears to recruit host
      (i.e. murine) stromal cells to invade the tumor and support its growth. In
      summary, normal ovarian stromal cells can inhibit ovarian tumor progression and
      the developing tumors recruit adjacent host stroma to become "tumor stroma". The
      tumor stroma likely develop an altered phenotype that cooperates with the
      tumorigenic epithelial cells to help promote the progression of ovarian cancer.

PMID- 11325515
TI  - Ovine caveolin-1: cDNA cloning, E. coli expression, and association with
      endothelial nitric oxide synthase.
AB  - Caveolin-1 (Cav-1), the principal coat protein of caveolae, plays an obligatory
      role in regulating the activity of endothelial nitric oxide (NO) synthase (eNOS).
      We propose that Cav-1 may be critical to eNOS-NO mediated uterine vasodilatation
      during pregnancy and estrogen replacement therapy. To test this hypothesis in the
      sheep model, we isolated the full-length cDNA of ovine Cav-1 (oCav-1) from a
      Lambda ZAP cDNA library of ovine placental artery endothelial cells. Thirty-two
      positive oCav-1 clones were recognized by a partial oCav-1 cDNA from this
      library, of which eight were sequenced. Restriction digestion of these clones
      revealed that the cDNAs of oCav-1 ranged from approximately 2.1 to 2.7 kb.
      Northern analysis of Cav-1 mRNAs in ovine uterine artery endothelial cells (UAEC)
      showed two transcripts of approximately 2.1 and 2.7 kb, respectively.
      Immunoreactive Cav-1 protein, but not caveolin-2 or caveolin-3, was detected in
      UAEC. Sequence analysis revealed that in addition to a 537-bp open reading frame
      encoding a 178 amino acid oCav-1 protein, full-length oCav-1 cDNAs apparently
      possess a approximately 1.6-2.1 kb 3'-untranslated region. Database searches with
      oCav-1 cDNA revealed that the coding region of mammalian Cav-1 genes is highly
      conserved. We prepared a recombinant full-length oCav-1 protein in which six
      consecutive histidine residues were tagged at the end of its COOH-terminus and
      developed a [His]6-tagged oCav-1 'pull-down assay' for studying the association
      of eNOS with Cav-1. Incubation of exogenous [His]6-tagged oCav-1 with resting
      UAEC extracts led to the formation of a [His]6-tagged oCav-1-eNOS complex. In the
      presence of a synthetic caveolin-scaffolding domain (CSD, aa 82-101) peptide, but
      not a mutated CSD peptide, [His]6-tagged oCav-1 associated eNOS was dose (0-10
      microM)-dependently inhibited. eNOS association with Cav-1 in UAEC was further
      confirmed by the facts that eNOS co-immunoprecipitated with Cav-1 and vice versa,
      and that eNOS co-existed with Cav-1 during the isolation of caveolae membranes.
      Because dissociation of eNOS from Cav-1 is required for the activation of eNOS,
      eNOS association with Cav-1 in UAEC suggests an important role of Cav-1 in
      regulating UAEC production of NO and possibly NO-mediated uterine vasodilatation.

PMID- 11325516
TI  - Metabolic and functional studies on isolated islets in a new rat model of type 2
      diabetes.
AB  - In a new experimental type 2 diabetic syndrome, a 40% reduction of pancreatic
      beta cells was observed by morphometric analysis. In diabetic islets, as compared
      to control islets, insulin release was decreased in response to high glucose but
      not to other stimuli, and total glucose oxidation and utilization were unchanged
      or slightly reduced. The extent of metabolic and functional impairment appeared
      proportional to the beta-cell loss. However, a substantial decrease was found in
      protein level and activity (by 77 and 60%, respectively, versus controls) of
      mitochondrial FAD-glycerophosphate dehydrogenase (mGDH), the key enzyme of the
      glycerophosphate shuttle. Interestingly, in diabetic islets, as recently reported
      for mGDH-deficient transgenic mice, definite functional alterations (mainly in
      response to D-glyceraldehyde) were only obtained upon pharmacological blockade of
      the second shuttle (i.e. malate-aspartate) responsible for mitochondrial transfer
      of reducing equivalents. In conclusion, in this diabetes model with reduction of
      beta-cell mass, the islets, despite decreased mGDH amount and activity, appear
      metabolically and functionally active in vitro, likely through the intervention
      of adaptive mechanisms, yet prone to failure in challenging situations.

PMID- 11325517
TI  - Repression of glucocorticoid receptor gene transcription by c-Jun.
AB  - The regulation of glucocorticoid receptor gene expression by members of the AP-1
      family was examined in glucocorticoid-free NIH3T3 cells transfected with the
      human glucocorticoid receptor gene promoter driving expression of a CAT reporter
      gene. c-Jun inhibited the promoter activity by 80% and JunB by 30%, whereas c-Fos
      and JunD had no inhibitory effect. Electrophoretic mobility shift assays showed
      that c-Jun is unable to efficiently interact with the AP-1-like site present in
      the human glucocorticoid receptor promoter. Moreover, c-Jun was still able to
      repress promoter mutants in which the region containing the AP-1-like site was
      deleted. NIH3T3 cell clones overexpressing c-Jun exhibited lower glucocorticoid
      receptor mRNA levels, which suggests that the murine glucocorticoid receptor gene
      can also be regulated by AP-1. These results provide a new mechanism for cross
      talk between the glucocorticoid receptor and the AP-1 family of transcription
      factors in the absence of glucocorticoid ligands.

PMID- 11325518
TI  - Chemokines control fat accumulation and leptin secretion by cultured human
      adipocytes.
AB  - In addition to their role in inflammation, cytokines like TNFalpha have been
      reported to regulate the adipose tissue function suggesting a role for these
      soluble mediators in metabolism. However, it is not known whether adipocytes have
      the capacity to secrete chemokines, a group of low molecular weight inflammatory
      mediators that control leukocyte migration into tissues. Here we show that
      primary cultures of human preadipocytes constitutively produce three chemokines,
      interleukin-8 (IL-8), macrophage inflammatory protein-1alpha (MIP-1alpha) and
      monocyte chemotactic protein-1 (MCP-1), while their level of expression is low in
      mature adipocytes. Upon TNFalpha treatment, the expression of all the three
      chemokines is upregulated in adipocytes differentiated in vitro. In addition, we
      describe the presence of seven different chemokine receptors, mainly in mature
      adipocytes, both in vitro and in human fat tissue sections. Prolonged stimulation
      of cultured human adipocytes with exogenous chemokines leads to a decrease in
      lipid content in association with the downregulation of PPARgamma mRNA
      expression. Moreover, chemokines positively control the secretion of leptin, a
      hormone that regulates appetite, by a post-transcriptional mechanism. These
      findings reveal a new role for chemokines in the regulation of adipose tissue and
      suggest a novel therapeutic basis for the treatment of obesity, diabetes and
      cachexia.

PMID- 11325519
TI  - Long-term variations of AP-1 composition after CRH stimulation: consequence on
      POMC gene regulation.
AB  - It has been shown previously that the CRH-induced POMC gene transcription in the
      corticotroph cell line AtT-20 involves an increase in AP-1 DNA binding activity
      that remained elevated for at least 24 h, while induction of c-fos was transient.
      We showed here that there were dramatic changes in protein components of AP-1
      including an initial recruitment of the transcriptional activators c-Fos and Jun
      B then of Fra-2 and Jun-D. Changes in AP-1 composition were concomitant with a
      decrease in POMC mRNA. Moreover, the presence of Fra-2/Jun-D dimers suppressed
      the CRH-induction of c-fos mRNA expression as well as c-Fos/Jun-B recruitment in
      AP-1 complexes, suggesting the existence of autoregulatory loops of AP-1
      composition that involve complex interactions between the different members of
      the Jun and Fos families. It is concluded that CRH stimulation of corticotroph
      cells involves successive recruitment of activators and repressors, possibly
      contributing to prevent over expression of POMC.

PMID- 11325520
TI  - The dissociation rate of estrogen receptor alpha from the consensus estrogen
      response element.
AB  - The rate of dissociation of recombinant, purified human estrogen receptor alpha
      (ERalpha) from a fluorescein-labeled DNA containing the consensus vitellogenin
      ERE sequence (F-vitERE) was determined in real time using fluorescence
      anisotropy. The complex of estradiol-occupied ERalpha with F-vitERE had an
      apparent dissociation rate of 1.48+/-0.06x10(-2) s(-1) and a half-life of 46.6 s
      at room temperature. The dissociation rate was characterized by a single
      exponential decay, suggesting that ER dissociates from the DNA as a preformed
      dimer, rather than as two individual monomers. The association rate of estradiol
      occupied ERalpha for the F-vitERE was calculated as 7x10(6) M(-1) s(-1) based on
      the dissociation rate measured and previous determinations of the equilibrium
      dissociation constant (Kd) in similar assay conditions (Ozers et al., 1997). In
      buffer containing various concentrations of salt, the rate of dissociation of
      estradiol-occupied ERalpha from F-vitERE was accelerated by increasing salt
      concentrations. Compared to estradiol-occupied ERalpha, the rate of dissociation
      of unoccupied ERalpha from the F-vitERE was very similar, indicating that
      estradiol occupancy does not affect the dissociation rate of ERalpha from the
      ERE.

PMID- 11325522
TI  - Basic fibroblast growth factor induces primordial follicle development and
      initiates folliculogenesis.
AB  - The recruitment of primordial follicles to initiate folliculogenesis determines
      the population of developing follicles available for ovulation and directly
      regulates female reproductive efficiency. In the current study, a floating organ
      culture system was used to examine the progression of primordial (stage 0)
      follicles to developing (stages 1-4) follicles in 4-day-old pre-pubertal rat
      ovaries. Basic fibroblast growth factor (bFGF) was found to induce primordial
      follicle development similar to what has been demonstrated for kit ligand/stem
      cell factor (KL). The bFGF-treated ovaries contained 85% developing follicles
      compared with 50% developing follicles for control untreated organ cultures.
      Correspondingly, the number of primordial follicles in bFGF-treated ovaries
      decreased to 15% of the total compared with 45% for controls. A bFGF neutralizing
      antibody was found to decrease the small amount of spontaneous follicle
      development that occurs during the organ culture. Basic FGF was localized to
      primordial and early developing follicles by immunocytochemistry and was
      primarily observed in the oocytes. Treatment of bovine ovarian theca cells and
      stroma cells with bFGF was found to promote cell growth. Basic FGF produced by
      the oocyte in early stage follicles appears to act on adjacent somatic cells to
      promote cell growth and development. Basic FGF, like KL, appears to be a
      primordial follicle-inducing factor. In summary, bFGF can regulate primordial
      follicle development that directly influences female reproductive efficiency.

PMID- 11325521
TI  - Smads in human trophoblast cells: expression, regulation and role in TGF-beta
      induced transcriptional activity.
AB  - Smad proteins have recently been shown to be downstream signaling molecules that
      transduce TGF-beta signals from cell surface to the nucleus. To determine the
      mechanisms of TGF-beta action in human trophoblast cells, we investigated the
      expression and regulation of Smad2,3,4, and 7 mRNAs in a normal trophoblast cell
      line, NPC, and a cell line derived from choriocarcinoma, JEG-3. Messenger RNAs
      for Smad2,3,4 and 7 were detected in both NPC and JEG-3 cells. TGF-beta1 induced
      modest increases in Smad2 and Smad4 mRNA levels without affecting Smad3 mRNA
      expression in both cell lines. Significant increases in Smad7 mRNA levels in both
      NPC and JEG-3 cells following TGF-beta1 treatment were observed. TGF-beta1 also
      induced promoter activity of the Smad7 gene, indicating a direct effect at the
      level of gene transcription. The transcriptional activity of TGF-beta was
      examined in JEG-3 cells using two TGF-beta responsive reporter constructs, p3TP
      Lux and pAR3-Lux. We found that Smad3 and to a lesser extent, Smad2 and Smad4,
      enhanced, while Smad7 inhibited, TGF-beta1-induced transcriptional activities.
      The basal and TGF-beta1-induced transcription can be blocked by overexpression of
      a dominant negative TGF-beta type II receptor. Taken together, these findings
      demonstrate that in human trophoblast cell lines, the Smad pathway involved in
      TGF-beta signal transduction is functional and that TGF-beta plays an autocrine
      role in regulating gene expression.

PMID- 11325524
TI  - Extracellular matrix components regulate ACTH production and proliferation in
      corticotroph tumor cells.
AB  - The extracellular matrix (ECM) conveys signals through membrane receptors called
      integrins producing changes in cell morphology, proliferation, differentiation
      and apoptosis. Previous studies suggest that the ECM plays an important role in
      pituitary physiology and tumorigenesis. In the present work we studied for the
      first time the effects of fibronectin, laminin, collagen I and collagen IV on
      hormone secretion and cell proliferation in the corticotroph tumor cell line AtT
      20 and in normal pituitary cells, examining the signal transduction mechanisms
      that mediate these effects. ACTH production in AtT-20 cells was inhibited by
      fibronectin, laminin and collagen I. A reporter construct with the POMC promoter
      showed similar results, indicating that the effects of the ECM take place at the
      level of POMC gene transcription. In contrast, ACTH production was not
      significantly altered in normal pituitary cells. AtT-20 cell proliferation was
      stimulated by collagen IV and fibronectin, but inhibited by collagen I and
      laminin. In parallel, the cell morphology was modified by the ECM. We found that
      the production of reactive oxygen species mediate the effects of laminin and
      collagen IV. On the other hand, the effect of fibronectin was mimicked by beta1
      integrin and Rho activation. These results show for the first time that the ECM
      controls ACTH biosynthesis and proliferation in corticotroph tumor cells and
      suggest a role for the ECM in corticotroph adenoma development.

PMID- 11325523
TI  - Modulation of insulin-stimulated glycogen synthesis by Src Homology Phosphatase
      2.
AB  - We have examined the requirement of the protein tyrosine phosphatase Src Homology
      Phosphatase 2 (SHP2) for insulin-stimulated glycogen synthesis. To this end,
      3T3L1 fibroblasts were stably transfected with either wild type or a
      catalytically inactive C463A-mutant of SHP2, and analysed for insulin-induced
      glycogen synthesis, tyrosine phosphorylation of the insulin receptor and IRS-1,
      and activation of phosphatidylinositol 3'-kinase (PI 3'-kinase). Glycogen
      synthesis was stimulated 9.1+/-0.9-fold by insulin in untransfected cells. In
      cells expressing the dominant-negative C463A-SHP2 mutant, the stimulation of
      glycogen synthesis by insulin was strongly enhanced (18.7+/-2.7-fold
      stimulation), while this response was impaired in cells overexpressing wild-type
      SHP2 (6.6+/-1.1-fold stimulation). When exploring the early post-receptor
      signalling pathways that contribute to glycogen synthesis, we found that insulin
      stimulated the tyrosine phosphorylation of IRS-1, and the activation of IRS-1
      associated PI 3'-kinase more strongly in C463A-SHP2 expressing 3T3L1-cells
      (18.1+/-4.7-fold) than in parental 3T3L1 cells (6.8+/-0.5-fold). In 3T3L1 cells
      overexpressing wild-type SHP2, the insulin stimulation of IRS-1 tyrosine
      phosphorylation and the activation of PI 3'-kinase (4.5+/-1.0-fold) were
      impaired. An enhanced activity of SHP2 leads to negative modulation of insulin
      signalling by reducing the tyrosine phosphorylation of IRS-1 and the concomitant
      activation of PI 3'-kinase. This results in an impaired ability of insulin to
      stimulate glycogen synthesis.

PMID- 11325525
TI  - KN-93 inhibition of G protein signaling is independent of the ability of
      Ca2+/calmodulin-dependent protein kinase II to phosphorylate phospholipase Cbeta3
      on 537-Ser.
AB  - Stimulation of the phospholipase Cbeta (PLC) signaling pathway results in
      intracellular Ca2+ release and subsequent activation of calmodulin (CaM) and CaM
      kinase II (CaMK II). KN-93, an inhibitor of CaMK II, reduced the stimulation of
      phosphatidylinositide (PI) turnover by Galphai-coupled (formyl-Met-Leu-Phe, fMLP)
      or Galphaq-coupled [M1 muscarinic and oxytocin (OT)] receptors. The inhibitory
      effect of KN-93 was also observed when PLCbeta3 was stimulated directly by
      Galphaq or Gbetagamma in overexpression assays. CaMK II phosphorylated PLCbeta3
      but not PLCbeta1 in vitro. Phosphorylation occurred exclusively on 537Ser in the
      X-Y linker region of PLCbeta3. 537Ser was also phosphorylated in the basal state
      in cells and phosphorylation was enhanced by ionomycin treatment. However,
      mutation of 537Ser to Glu had no effect on inhibition of Galphaq or Gbetagamma
      stimulated PLCbeta3 activity by KN-93. KN-93 also inhibited Galphaq -stimulated
      PLCbeta1 activity, even though this enzyme is not a substrate for CaMK II. These
      data indicate that phosphorylation of PLCbeta3 by CaMK II is not directly
      involved in the inhibitory effect of KN-93 on phosphatidylinositide turnover.

PMID- 11325526
TI  - Role of membrane depolarization and T-type Ca2+ channels in angiotensin II and K+
      stimulated aldosterone secretion.
AB  - The hypothesis that Ca2+ influx necessary for angiotensin II (AngII) and K+
      stimulation of aldosterone secretion is primarily mediated by membrane
      depolarization and activation of T-type Ca2+ channels was examined in isolated
      rat adrenal glomerulosa cells. Perforated-patch clamp recordings of membrane
      potential (Vm) demonstrated that AngII and K+ induce concentration-dependent
      depolarizations capable of activating T channels and, at high K+ and AngII
      concentrations, activating L channels and inactivating T channels. K+-induced
      depolarizations were stable and readily reversible. Vm was proportional to K+
      concentration, exhibiting a linear slope of 53.7 mV per 10-fold increase in K+.
      AngII-induced depolarizations were complex, consisting of a slow maintained
      component superimposed with small amplitude depolarizing fluctuations. Slow
      oscillations in Vm were occasionally observed in response to 10(-9) M AngII or
      greater. The slow, maintained component of depolarization coincided with
      inhibition of K+ conductance. Neither rapid fluctuations nor slow oscillations in
      Vm were blocked by mibefradil or other treatments that inhibit voltage-gated Ca2+
      channels. Perforated-patch clamp experiments also demonstrated that AngII (10(-8)
      M) inhibited L channels by 45.6% without affecting T channels. Thus AngII
      activates T channels by depolarization rather than T channel modulation in rat
      cells. The concentration dependencies of mibefradil inhibition of T channels and
      AngII- and K+-induced aldosterone secretion were compared. Under whole-cell patch
      clamp mibefradil induced a concentration-dependent inhibition of T channels,
      exhibiting a K(app) of 0.62 microM. Mibefradil inhibition was use-dependent but
      mibefradil neither acted as an open channel blocker nor significantly affected T
      channel inactivation or activation. Mibefradil inhibited K+- and AngII-induced
      secretion at concentrations similar to that for T channel inhibition; at high
      concentrations (10 microM) mibefradil inhibited AngII-induced secretion by 88%
      and completely inhibited K+-induced secretion. The IC50 for K+-induced secretion
      was dependent on K+ concentration, increasing from 0.2 microM for 6 mM K+ to 2.5
      microM for 10 mM K+ or greater. Mibefradil exhibited an IC50 of 1.1 microM for
      inhibition of secretion at all AngII concentrations examined (0.1, 1.0, and 10
      nM). Mibefradil also exhibited multiple nonspecific effects, which complicated
      the assessment of T channel function, including; inhibition of leak and voltage
      dependent K+ conductances, inhibition of Ca2+-independent aldosterone secretion,
      and inhibition of secretion under conditions expected to completely inactivate T
      channels (10 nM AngII or 20 mM K+). In summary, these results indicate that
      voltage-gated T channels represent the primary Ca2+ influx pathway activated by
      physiological concentrations of AngII and K+ but other Ca2+ influx pathways must
      mediate aldosterone secretion induced by high K+ or AngII concentrations.

PMID- 11325527
TI  - Dysregulation of mammary Stats 1,3 and 5 and PRL receptors by overexpression of
      TGFalpha.
AB  - Mammary TGFalpha overexpression results in delayed involution and eventually
      mammary cancer in transgenic mice. We hypothesized that STATs and PRL receptors
      (PRLR), critical regulators of mammary function, are altered in these animals and
      may contribute to this phenotype. We examined these factors late in the first
      pregnancy (d.18) and during normal involution (d.4 post-lactation) in WAP
      TGFalpha transgenic mice and non-transgenic controls. Long form PRLR mRNA in WAP
      TGFalpha glands at both pregnant d.18 and d.4 post-lactation was significantly
      reduced compared to controls, and PRLR-S3 failed to rise during involution. Total
      and pTyr STAT 1,3,5a and 5b also were altered. STAT 3 was higher at both times in
      WAP-TGFalpha glands. STAT 5a and 5b were lower at late pregnancy, but higher post
      lactation; however, pTyr(694) STAT 5 was abnormally low at both times. Thus
      overexpression of TGFalpha has direct or indirect effects on both STATs and PRL
      responsiveness in vivo, which may reflect mechanisms of TGFalpha-induced mammary
      epithelial abnormalities.

PMID- 11325528
TI  - Regulation of the ErbB3 binding protein Ebp1 by protein kinase C.
AB  - Ebp1, a 47 kDa ubiquituously expressed protein, binds the ErbB3 receptor in human
      serum starved breast cancer cell lines and dissociates from ErbB3 on treatment
      with the ErbB3 ligand, Heregulin (HRG). However, the mechanism of Ebp1-ErbB3
      association/dissociation is not understood. Since Ebp1 contains six putative
      Protein Kinase C serine/threonine phosphorylation sites, we examined the ability
      of PKC to phosphorylate Ebp1 and to regulate Ebp1-ErbB3 binding. We found that
      Ebp1 was basally phosphorylated in AU565 breast cancer cells on serine/threonine
      residues and that this phosphorylation was enhanced by heregulin treatment. Both
      serine and threonine residues of a GST-Ebp1 fusion protein were phosphorylated by
      PKC in vitro. In vivo, we demonstrated that basal Ebp1 phosphorylation was
      dependent upon PKC. However, HRG-induced phosphorylation of Ebp1 occurred
      predominantly in a PKC-independent manner. The ability of Ebp1 to associate with
      ErbB3 in serum-starved NIH3T3 cells overexpresssing ErbB3 was abrogated by
      treating cells with a PKC inhibitor. These findings suggest that PKC plays a role
      in regulating phosphorylation and function of Ebp1 in vivo.

PMID- 11325529
TI  - Somatostatin actions on a protein kinase C-dependent growth hormone secretagogue
      cascade.
AB  - In mammals, the ability of somatostatin (SS) to block growth hormone (GH)
      secretion is due, in part, to the inhibition of two key intracellular mediators,
      cAMP and Ca2+. We examined whether or not inhibition of Ca2+ signaling was
      mediating SS-induced inhibition basal, as well as gonadotropin-releasing hormone
      (GnRH; a protein kinase C (PKC)-dependent growth hormone secretagogue)-stimulated
      growth hormone (GH) release. Although SS reduced basal GH release from
      populations of pituitary cells, parallel reductions in [Ca2+]i were not observed
      within single, identified somatotropes. Similarly, application of GnRH and the
      PKC activator DiC8 elicited increases in [Ca2+]i and GH release, but abolition of
      the Ca2+ responses did not accompany SS inhibition of the GH responses.
      Surprisingly, while DiC8 potentiated SS inhibition of GH release, SS
      paradoxically increased DiC8-stimulated increases in [Ca2+]i. These data
      establish that abolition of Ca2+ signals is not a primary mechanism through which
      SS lowers basal, or inhibits GnRH-stimulated hormone release.

PMID- 11325530
TI  - Action of hormone responsive sequence in 2.3 kb promoter of CYP11A1.
AB  - The CYP11A1 gene encodes cytochrome P450scc, the enzyme catalyzing the first step
      of steroid biosynthesis in the adrenal and gonad. We generated transgenic mice
      containing 2.3 kb of the 5'-flanking region of CYP11A1 driving LacZ reporter gene
      expression, in order to study hormonal control of CYP11A1 gene expression in
      different tissues. This 2.3 kb fragment contains information for hormonal
      control; by ACTH and hCG which increased reporter gene expression, in the adrenal
      and testis of transgenic mice respectively, while dexamethasone administration
      decreased reporter activity in the adrenal. The 5'-fragment of CYP11A1 has
      appreciable promoter activities in mouse adrenal Y1 cells but not in non
      steroidogenic COS-1 cells, showing cell-type specificity. Transcription factor SF
      1 activates the 2.3 kb promoter, which can be potentiated by cotransfection with
      c-Jun in steroidogenic JEG3 cells but not in COS-1 cells. We conclude that the
      2.3 kb region of CYP11A1 contains elements controlling hormonal-dependent, cell
      type-specific expression. In addition, c-Jun and SF-1 could act synergistically
      to activate CYP11A1 gene expression.

PMID- 11325531
TI  - Transactivation of the IGFBP-2 promoter in human tumor cell lines.
AB  - Many cancers produce high amounts of the insulin-like growth factor binding
      protein (IGFBP)-2, which can influence the tumorigenicity and growth of tumor
      cells. In order to study the possible cause of elevated expression of IGFBP-2 in
      tumors, we investigated the transcriptional regulation by IGF of a 633-bp
      fragment of the human IGFBP-2 promoter in a transiently transfected
      choriocarcinoma (JAR) and a leukemic T-cell line (Molt-4) that express IGFBP-2
      highly, and in a leukemic B-cell line (Raji) that expresses little IGFBP-2.
      Strong basal promoter activity, i.e. luciferase activity was measurable in all of
      the tumor cell lines. The introduction of equal amounts of normal IGF-I and IGF
      II stimulated the transcription of IGFBP-2 only slightly. Synthetic IGF analogues
      with increased biological activity, however, caused a specific 2.0-3.3-fo1d
      transactivation of the promoter, as well as a 25% increase in IGFBP-2 mRNA.
      Synchronously, IGF analogues caused a decrease in the level of IGFBP-3 mRNA of
      about 45%, while the production of IGFBP-2 as measured by RIA increased in
      relation to IGFBP-3 by up to 15 times. Blocking with the IGF antagonist JB1
      revealed partial involvement of the IGF-I receptor in the regulation of IGFBP-2
      expression by locally produced IGF. We conclude, that the reduced ability of IGF
      analogues to form complexes with locally produced IGFBP may account for their
      increased biological activity in the stimulation of expression of IGFBP-2 and of
      cell growth. Since increased biological activity had also been demonstrated for
      natural pro-IGF forms often produced by tumors, pro-IGFs may be involved in the
      mechanism leading to elevated IGFBP-2 expression of tumors in vivo.

PMID- 11325532
TI  - Steady-state kinetics of MgATP splitting by native myosin RLC-free subfragment 1.
AB  - MgATP positively regulates the dimerisation reaction, resulting in an increase in
      the rate of MgATP splitting with increasing MgATP concentration. We investigated
      the stoichiometry of this dimerisation reaction and found that each subunit in
      the dimer bound one molecule of MgATP at the dimerisation site. We studied
      changes with temperature in the MgATPase activity of S1 in the dimeric form for
      temperatures of 18-25 degrees C. Between 18.0 and 21.2 degrees C, kcat increased
      steadily with temperature. Between 21.2 and 21.8 degrees C, there was a large
      decrease in kcat. A strong increase in kcat occurred at temperatures above 21.8
      degrees C, corresponding to a new reversible conformation of S1, unable to
      dimerise. The steep decrease in kcat between 21.2 and 21.8 degrees C is due to a
      temperature transition in the monomer-dimer equilibrium.

PMID- 11325533
TI  - The simulated microgravity environment maintains key metabolic functions and
      promotes aggregation of primary porcine hepatocytes.
AB  - The high aspect ratio vessel allows the culture of primary porcine hepatocytes in
      an environment of low shear stress and simulated microgravity. Primary porcine
      hepatocytes have been difficult to maintain in culture long term while preserving
      their metabolic functions. This study was carried out in order to characterise
      key metabolic functions of cell aggregates formed by primary porcine hepatocytes
      cultured in a high aspect ratio vessel for a predetermined period of 21 days.
      10(8) porcine hepatocytes were loaded into the high aspect ratio vessel and
      continuously rotated during the experiments. 0.7 ml of the culture medium was
      sampled on days 1, 2, 4, 7, 10, 14 and 21. 1H nuclear magnetic resonance
      spectroscopy of the culture medium, using the presaturation technique, assessed
      the following: glucose metabolism, glutamine synthesis and ketogenesis. There was
      glucose breakdown anaerobically during the first 10 days as manifested by lactate
      production and pyruvate and threonine consumption. After day 10 there was
      significantly smaller lactate production (day 1 vs day 10 P < 0.01), and
      significantly smaller pyruvate (day 1 vs day 14 P < 0.03) and threonine
      consumption (day 1 vs day 10 P < 0.002), indicative of an aerobic metabolic
      pattern. Significantly more glutamate was produced after day 10 (day 1 vs day 10
      P < 0.031), and more glutamine was consumed after day 14. There was a steadily
      diminishing production of acetate which reached a minimum on day 14 (day 2 vs day
      14 P < 0.00014). After an initial 10 day period of acclimatisation cell
      aggregates formed in the high aspect ratio vessel switched from the anaerobic
      pattern of metabolism to the more efficient aerobic pattern, which was exhibited
      until the experiments were terminated. The high aspect ratio vessel is suitable
      for long-term culture of porcine hepatocytes and it is worthwhile carrying out
      scale-up feasibility studies.

PMID- 11325534
TI  - Isolation and characterization of four bactericidal domains in the bovine beta
      lactoglobulin.
AB  - Proteolytic digestion of bovine beta-lactoglobulin by trypsin yielded four
      peptide fragments with bactericidal activity. The peptides were isolated and
      their sequences were found as follows: VAGTWY (residues 15-20), AASDISLLDAQSAPLR
      (residues 25-40), IPAVFK (residues 78-83) and VLVLDTDYK (residues 92-100). The
      four peptides were synthesized and found to exert bactericidal effects against
      the Gram-positive bacteria only. In order to understand the structural
      requirements for antibacterial activity, the amino acid sequence of the peptide
      VLVLDTDYK was modified. The replacement of the Asp (98) residue by Arg and the
      addition of a Lys residue at the C-terminus yielded the peptide VLVLDTRYKK which
      enlarged the bactericidal activity spectrum to the Gram-negative bacteria
      Escherichia coli and Bordetella bronchiseptica and significantly reduced the
      antibacterial capacity of the peptide toward Bacillus subtilis. By data base
      searches with the sequence VLVLDTRYKK a high homology was found with the peptide
      VLVATLRYKK (residues 55-64) of human blue-sensitive opsin, the protein of the
      blue pigment responsible for color vision. A peptide with this sequence was
      synthesized and assayed for bactericidal activity. VLVATLRYKK was strongly active
      against all the bacterial strains tested. Our results suggest a possible
      antimicrobial function of beta-lactoglobulin after its partial digestion by
      endopeptidases of the pancreas and show moreover that small targeted
      modifications in the sequence of beta-lactoglobulin could be useful to increase
      its antimicrobial function.

PMID- 11325535
TI  - Chondrocyte deformation within mechanically and enzymatically extracted chondrons
      compressed in agarose.
AB  - Within articular cartilage, the chondron microenvironment will influence
      chondrocyte behaviour and response to loading. Chondrons were extracted from
      intact cartilage using either mechanical homogenisation (MC) or enzymatic
      digestion (EC) and cell and matrix morphology in unstrained and compressed
      agarose constructs was examined. Isolated chondrocytes (IC) were used for
      comparison. Immunolocalisation of type VI collagen and keratan sulphate revealed
      differences in the structure of the pericellular microenvironment such that MC
      most closely resembled chondrons in situ. The unstrained cell diameters of IC and
      EC were larger than MC at day 1 and increased significantly over a 7 day culture
      period. In contrast, cell diameters for MC remained constant. Compression of
      constructs at day 1 resulted in cell deformation for IC and EC but not MC. The
      two chondron extraction methods yielded chondrons of differing matrix morphology
      and associated differences in cell size and cellular response to load. The
      results indicate that the pericellular microenvironment of MC initially possessed
      a greater mechanical integrity than that of EC. Although these differences may be
      reduced with time in culture, characterisation of mechanically isolated chondrons
      suggests that the stiffness of the chondrons in situ may be greater than previous
      estimates.

PMID- 11325537
TI  - Unusually large numbers of electrons for the oxidation of polyphenolic
      antioxidants.
AB  - Reaction mechanisms of polyphenolic antioxidants were studied using
      electrochemical methods (flow column electrolysis and cyclic voltammetry). In
      flow column electrolysis, the numbers (ns) of electrons involved in the oxidation
      of catechols (chlorogenic acid and caffeic acid) became larger than two (i.e. the
      number of -OH moieties) at pH > 7; the n-values finally reached ca. 4 at pH 10.
      Other polyphenols including catechin, ellagic acid, and curcumin exhibited higher
      n-values than the numbers of -OH moieties in the whole pH range studied (4 < pH <
      10). Such unusually large n-values for polyphenols were found to correlate to
      their irreversible behavior in cyclic voltammetry. A digital simulation analysis
      of the voltammograms of chlorogenic acid clearly showed that the electrode
      reaction at higher pHs can be elucidated in terms of a quasi-reversible electron
      transfer followed by a chemical reaction and also suggested that the chemical
      reaction is of second order to the concentration of chlorogenic acid, i.e. a
      dimerization reaction. In a similar manner, polyphenolic antioxidants generally
      undergo certain chemical reactions on the occasion of their oxidation. As a
      result, some oxidizable, phenolic -OH moieties are reproduced in the polymeric
      products. The unusually large n-values of polyphenols and thus their higher
      radical scavenging activities may be ascribed to such reproduction of -OH
      moieties by oxidative polymerization.

PMID- 11325536
TI  - Matrix metalloproteinase-1, -3, -13 and aggrecanase-1 and -2 are differentially
      expressed in experimental osteoarthritis.
AB  - The aim of this study was to characterize the cellular phenotypes of articular
      cartilage and meniscus in rabbits with experimentally induced osteoarthritis
      (OA), by histological and molecular biological techniques. OA was induced by
      severing the anterior cruciate ligament of the knee and rabbits were killed 2, 4
      or 9 weeks following surgery. Our histological observations show a progressive
      destruction of extracellular matrix in both tissues. To determine whether these
      morphological changes could be related to alterations in the regulation of gene
      expression for a subset of relevant molecules, levels of mRNA for proteinases and
      one inhibitor (MMP-1, -3 and -13, aggrecanase-1 and -2 and TIMP-1), matrix
      molecules and one chaperone (type II and X collagens, aggrecan, osteonectin,
      betaig-h3 and BiP) were assessed by reverse transcription-polymerase chain
      reaction. Our results indicate that for most markers expression profiles were
      similar in both tissues. In particular, matrix protein gene expression remained
      stable or varied little during progression of OA, suggesting a poor repair
      capacity of the tissues. MMP gene expression increased rapidly whereas
      aggrecanase gene expression remained stable. These findings suggest that
      differential regulation of mRNA levels of MMP-1, -3 and -13 on the one hand and
      aggrecanase-1 and -2 on the other, occurs during OA.

PMID- 11325538
TI  - Characterization of monoclonal antibodies against ascorbate peroxidase
      isoenzymes: purification and epitope-mapping using immunoaffinity column
      chromatography.
AB  - We have developed three monoclonal antibodies against spinach chloroplastic (chl
      mAb3 and chl-mAb6) and cytosolic (cyt-mAb1) ascorbate peroxidase (APX) isoenzymes
      to analyze the cross-reactivity and the structure of the epitopes for each
      monoclonal antibody. All three antibodies reacted specifically with their
      respective isoenzymes, but none cross-reacted with the others. Immunoreactive
      fragments in proteolytic recombinant APX isoenzymes were detected by means of the
      absorption on the corresponding immunoaffinity column. The cyt-mAb1 reacted with
      a peptide fragment containing the distal His region obtained by the lysyl
      endopeptidase digestion. The chl-mAb6 was capable of binding to the fragment, D-I
      K-E-K-R, which is consistent with an inherent region of chloroplastic isoenzymes.
      No fragments reacting to the chl-mAb3 could be found in this study, suggesting
      that the chl-mAb3 recognizes a conformationally constituted epitope of the
      chloroplastic APX molecule, which may be destroyed by the enzymatic cleavage. We
      concluded that the peptides identified as epitopes are characteristic evidence of
      monoclonal antibodies.

PMID- 11325539
TI  - Effects of sialic acid residues of transferrin on the binding with aluminum and
      iron studied by HPLC/high-resolution ICP-MS.
AB  - Transferrins (Tfs) are glycoproteins with carbohydrate chains in the C-lobe.
      Carbohydrate-deficient Tfs (CDTs) with fewer sialic acids increased in several
      diseases. In this study, the affinity of metals (Al and Fe) to Tfs was compared
      between native- and asialo-Tf by on-line high-performance liquid
      chromatography/high-resolution inductively coupled plasma mass spectrometry, to
      clarify whether the presence of sialic acids influences the metal binding. Fe
      added as Fe-citrate in the presence of bicarbonate preferred the N-lobe site and
      the binding affinity was similar between native- and asialo-Tfs. Al-citrate added
      at Al/Tf = 1 also preferred the N-lobe site, while the binding affinity was
      higher to asialo-Tf than to native-Tf. In Al-oxalate addition, the affinity to
      the N-lobe site of both Tfs increased further. In the absence of bicarbonate, Al
      oxalate showed a preference for the C-lobe site in native-Tf and comparable
      affinity to both lobes in asialo-Tf. In asialo-Tf, Al2-Tf was the largest peak
      even at Al/Tf = 1. Thus, the lack of sialic acid in glycans and the presence of
      oxalate enhanced the binding affinity of Al to Tf. Therefore, it was suggested
      that the binding affinity of Al in patients with CDTs may be enhanced.

PMID- 11325540
TI  - Discovery of a non-peptide small molecule that selectively mimics the biological
      actions of calcitonin.
AB  - Calcitonin (CT), a 32-amino acid peptide hormone secreted mainly from the thyroid
      gland, plays an important role in maintaining bone homeostasis. To discover non
      peptide small molecules with biological actions similar to those of CT, a cell
      based screening of an in-house chemical library was performed and a pyridone
      derivative (SUN B8155) was identified. Like CT, it elevated cyclic AMP (cAMP)
      levels in T47D and UMR106-06 cells which endogenously express human and rat CT
      receptor, respectively. SUN B8155 also stimulated cAMP formation in cells
      expressing recombinant human CT receptor, but not in those expressing human
      parathyroid hormone/parathyroid hormone-related peptide receptor. Accumulation of
      cAMP in T47D cells was blocked by a selective antagonist of CT receptor, salmon
      CT(8-32), whereas SUN B8155 did not displace the specific binding of [(125)I]CT
      to the receptor. Our results suggested that the compound selectively interacts
      with the CT receptor by a mechanism similar to but probably different from that
      of CT itself. In rats, intraperitoneal administration of SUN B8155 significantly
      lowered serum calcium levels, like CT. Our results demonstrate, for the first
      time, that the biological activities of the newly identified small molecule can
      mimic that of CT, acting via the CT receptor.

PMID- 11325541
TI  - Protective role of superoxide dismutases against ionizing radiation in yeast.
AB  - The protective role of superoxide dismutases (SODs) against ionizing radiation,
      which generates reactive oxygen species (ROS) harmful to cellular function, was
      investigated in the wild-type and in mutant yeast strains lacking cytosolic
      CuZnSOD (sod1Delta), mitochondrial MnSOD (sod2Delta), or both SODs
      (sod1Deltasod2Delta). Upon exposure to ionizing radiation, there was a distinct
      difference between these strains in regard to viability and the level of protein
      carbonyl content, which is the indicative marker of oxidative damage to protein,
      intracellular H2O2 level, as well as lipid peroxidation. When the oxidation of
      2',7'-dichlorofluorescin was used to examine the hydroperoxide production in
      yeast cells, the SOD mutants showed a higher degree of increase in fluorescence
      upon exposure to ionizing radiation as compared to wild-type cells. These results
      indicated that mutants deleted for SOD genes were more sensitive to ionizing
      radiation than isogenic wild-type cells. Induction and inactivation of other
      antioxidant enzymes, such as catalase, glucose 6-phosphate dehydrogenase, and
      glutathione reductase, were observed after their exposure to ionizing radiation
      both in wild-type and in mutant cells. However, wild-type cells maintained
      significantly higher activities of antioxidant enzymes than did mutant cells.
      These results suggest that both CuZnSOD and MnSOD may play a central role in
      protecting cells against ionizing radiation through the removal of ROS, as well
      as in the protection of antioxidant enzymes.

PMID- 11325542
TI  - Copper complexes of glycyl-histidyl-lysine and two of its synthetic analogues:
      chemical behaviour and biological activity.
AB  - Copper complex formation equilibria of glycyl-L-histidyl-L-lysine (Gly-His-Lys,
      GHK) and of two synthetic analogues, where the histidine residue was replaced
      with a synthetic amino acid (L-spinacine or L-1,2,3,4-tetrahydro-isoquinoline-3
      carboxylic acid), have been carefully investigated using different experimental
      techniques: potentiometry, solution calorimetry, UV-VIS spectrophotometry,
      circular dichroism and electron paramagnetic resonance spectroscopies. All the
      ligands formed complexes having different stoichiometries and stabilities;
      evidence for the formation of binuclear species is also shown. The structures of
      the main complexes are discussed. It is suggested that the lateral lysine amino
      group participates in complex formation, but only at alkaline pH values: at
      physiological pH this group is protonated and available for possible interactions
      with cellular receptors. The above tripeptides have been tested for their
      enzymatic stability in human serum: the synthetic compounds showed no significant
      degradation for at least 3 h. Finally, their activity as growth factor has been
      studied in vitro. The two synthetic analogues showed an activity comparable to or
      even higher than that of GHK, thus suggesting their possible use as additives in
      cell culture media, even in the presence of serum. Relevant information on the
      GHK action mechanism as cell growth factor has been obtained: the formation of
      copper complexes, driven by the first (Gly) residue, appears necessary while the
      second residue (His) does not appear to play a specific role; the presence of the
      free side chain of the third residue (Lys) appears to be of fundamental
      importance.

PMID- 11325543
TI  - Lsh, a SNF2 family member, is required for normal murine development.
AB  - Lsh is a member of the SNF2 family of chromatin remodelers, that regulate diverse
      biological processes such as replication, repair and transcription. Although
      expression of Lsh is highly tissue specific in adult animals, Lsh mRNA is
      detectable in multiple tissues during embryogenesis. In order to determine the
      physiologic role of Lsh during murine development and to assess its unique
      function in adult mice, we performed targeted deletion of the Lsh gene using
      homologous recombination in murine embryonic stem cells. Lsh-/- embryos occurred
      with the expected Mendelian frequency after implantation and during
      embryogenesis. However, Lsh-/- mice died within a few hours after birth.
      Furthermore, newborn mice were 22% lower in weight in comparison with their
      littermates and showed renal lesions. Thus Lsh is a non-redundant member of the
      SNF2 family and is essential for normal murine development and survival.

PMID- 11325544
TI  - Biliary excretion of polystyrene microspheres depends on the type of receptor
      mediated uptake in rat liver.
AB  - Hepatic uptake and biliary excretion of fluorescein isothiocyanate-labeled
      polystyrene microspheres with a particle size of 50 nm (MS-50) were studied in
      rats. Liver perfusion studies revealed that not only apo-E-mediated but also
      asialoglycoprotein receptor-mediated uptake is involved in the mechanism of the
      serum protein-dependent uptake of MS-50 in the liver. The uptake of MS-50
      mediated by apo-E contributes more to the total uptake of MS-50 by the
      hepatocytes than that via asialoglycoprotein receptor in the presence of serum in
      the perfusate. Furthermore, it was found that MS-50 is substantially excreted
      into the bile by transcytosis. The extent of exocytosis of MS-50 taken up by the
      hepatocytes was much higher after MS-50 was endocytosed via asialoglycoprotein
      receptor than after taken up via the process mediated by apo-E. On the basis of
      these results, a possible regulation of the intracellular sorting of ligands,
      depending on the receptor-mediated uptake mechanism, was inferred.

PMID- 11325545
TI  - Structure, function, and assembly of the terminal organelle of Mycoplasma
      pneumoniae.
AB  - Mycoplasmas are cell wall-less bacteria at the low extreme in genome size in the
      known prokaryote world, and the minimal nature of their genomes is clearly
      reflected in their metabolic and regulatory austerity. Despite this apparent
      simplicity, certain species such as Mycoplasma pneumoniae possess a complex
      terminal organelle that functions in cytadherence, gliding motility, and cell
      division. The attachment organelle is a membrane-bound extension of the cell and
      is characterized by an electron-dense core that is part of the mycoplasma
      cytoskeleton, defined here for working purposes as the protein fraction that
      remains after extraction with the detergent Triton X-100. This review focuses on
      the architecture and assembly of the terminal organelle of M. pneumoniae.
      Characterizing the downstream consequences of defects involving attachment
      organelle components has made it possible to begin to elucidate the probable
      sequence of certain events in the biogenesis of this structure.

PMID- 11325546
TI  - In vitro antibacterial activity of some aliphatic aldehydes from Olea europaea L.
AB  - In the present paper we report the 'in vitro' activity of eight aliphatic long
      chain aldehydes from olive flavor (hexanal, nonanal, (E)-2-hexenal, (E)-2
      eptenal, (E)-2-octenal, (E)-2-nonenal, (E)-2-decenal and (E,E)-2,4-decadienal)
      against a number of standard and freshly isolated bacterial strains that may be
      causal agents of human intestinal and respiratory tract infections. The saturated
      aldehydes characterized in the present study do not exhibit significant
      antibacterial activity, while the alpha,beta-unsaturated aldehydes have a broad
      antimicrobial spectrum and show similar activity against Gram-positive and Gram
      negative microorganisms. The effectiveness of the aldehydes under investigation
      seems to depend not only on the presence of the alpha,beta-double bond, but also
      on the chain length from the enal group and on the microorganism tested.

PMID- 11325547
TI  - PCR detection of Helicobacter pylori in string-absorbed gastric juice.
AB  - Molecular methods for detection of Helicobacter pylori infection have been shown
      to be highly sensitive in gastric biopsies and cultures. The objective of this
      work was to compare PCR detection of H. pylori DNA in string-absorbed gastric
      juice and in gastric biopsies. The study was performed in 47 dyspeptic adult
      patients undergoing endoscopy, and infection was detected by amplification of a
      segment of H. pylori ureA gene. Of the 29 patients positive in biopsy analysis,
      23 (79%) were also positive in the gastric string. PCR analysis of gastric
      strings is a sensitive and safe procedure to detect H. pylori when endoscopy is
      not indicated, and may be of great clinical and epidemiological usefulness in
      determining effectiveness of eradication therapies, typing virulence genes and
      detecting antibiotic resistance mutations.

PMID- 11325548
TI  - The detection of Shiga toxin-producing Escherichia coli in diagnostic bovine
      faecal samples using vancomycin-cefixime-cefsulodin blood agar and PCR.
AB  - The prevalence of complex Shiga toxin-producing Escherichia coli (STEC), i.e.
      STEC containing accessory virulence factors intimin (eaeA) and/or
      enterohaemorrhagic E. coli haemolysin (ehxA) and their serotypes were determined
      in diagnostic bovine faecal samples processed during a 3 months period. The
      presence of complex STEC was determined using PCR and vancomycin-cefixime
      cefsulodin blood agar (BVCCA) using a dual approach which involved (i) direct
      culture of faecal samples on BVCCA followed by mutiplex PCR of BVCCA positive
      colonies and (ii) culture of faecal samples enriched in modified EC (mEC) broth
      (with a complex STEC profile determined by PCR) on BVCCA followed by multiplex
      PCR of BVCCA positive colonies. Using both techniques complex STEC were isolated
      from 23 (18.7%) of the 123 faecal samples. Complex STEC were isolated from 14
      faecal samples by direct culture on BVCCA and 13 faecal samples yielded complex
      STEC by culture of mEC broths with a complex STEC profile on BVCCA. Only four
      samples were positive using both techniques. The serotypes isolated included O5:H
      , O26:H-, O26:H11, O91:H21, O111:H-, O111:H8, O104:H11, O113:H21 and O157:H8.
      This study confirms that non-O157 STEC can be isolated from bovine faeces and
      that they carry types associated with human disease. This work also demonstrates
      that the use of a dual approach is advisable to increase the likelihood of
      isolating complex STEC.

PMID- 11325549
TI  - Metabolite and enzyme profiles of glycogen metabolism in Methanococcoides
      methylutens.
AB  - When a buffered anaerobic cell suspension of Methanococcoides methylutens was
      maintained under methanol-limited conditions, intracellular glycogen and hexose
      phosphates were consumed rapidly and a very small amount of methane formed at 4 h
      of a starvation period. When methanol was supplemented after a total of 20 h of
      starvation, a reverse pattern was observed: the glycogen level and the hexose
      phosphate pool increased, and formation of methane took place after a lag period
      of 90 min. A considerable amount of methane was formed in 120 min after its
      detection with a rate of 0.18 micromol mg(-1) protein min(-1). When methane
      formation decreased after 270 min of incubation and finally came to a halt,
      probably due to complete assimilation of supplemented methanol, the levels of
      glycogen and hexose monophosphates decreased once again. However fructose 1,6
      diphosphate levels showed a continuous increase even after exhaustion of methane
      formation. In contrast to the hexose phosphate pool, levels of other metabolites
      showed a small increase after addition of methanol. The enzyme profile of
      glycogen metabolism showed relatively high levels of triose phosphate isomerase.
      Glyceraldehyde 3-phosphate dehydrogenase reacted with NADPH with a three-fold
      higher activity as compared to that with NADH.

PMID- 11325550
TI  - Assessment of the serodiagnostic potential of nine novel proteins from
      Mycobacterium tuberculosis.
AB  - To identify antigens that would improve the accuracy of serological diagnosis of
      active tuberculosis, we cloned the genes encoding nine potentially immunogenic
      secreted or surface-associated proteins of Mycobacterium tuberculosis.
      Recombinant proteins were reacted with sera from HIV-negative individuals with
      extrapulmonary tuberculosis (EP-TB) or HIV-positive individuals with pulmonary
      tuberculosis (TBH). Specific and high level antibody responses were obtained for
      four recombinant proteins, of which antigen GST-822 was recognized by 60% of EP
      TB and 42% of TBH and antigen MBP-506 was recognized by 45% of EP-TB and 61% of
      TBH. These results suggest that these proteins are strong candidates as subunits
      in a polyvalent serodiagnostic test.

PMID- 11325551
TI  - Involvement of aspirin-sensitive oxylipins in vulvovaginal candidiasis.
AB  - 3(R)-Hydroxyoxylipins are produced via an aspirin-sensitive pathway in Candida
      albicans, an abundant pathogen in vulvovaginal candidiasis. In the present study,
      we have investigated the effect of aspirin on vaginal isolates of C. albicans
      from patients with recurrent candidiasis. Aspirin alone and with clotrimazole, a
      commonly used drug, strongly suppressed growth of C. albicans. 3(R)
      Hydroxyoxylipins, which were selectively located in hyphae and other filamentous
      structures, but not in free blastospores, were almost totally suppressed by
      aspirin. Moreover, C. albicans stimulated prostaglandin E(2) (PGE(2)) production
      in HeLa cells. PGE(2) is a stimulus for germ tube formation in C. albicans. We
      conclude therefore that the administration of aspirin should be beneficial in the
      treatment of vulvovaginal candidiasis by dual ways: (i) by inhibition of 3(R)
      hydroxyoxylipin formation, and (ii) by inhibition of PGE(2) formation in the
      infected host tissue.

PMID- 11325552
TI  - Use of molecular markers to differentiate between commercial strains of the
      button mushroom Agaricus bisporus.
AB  - Agaricus bisporus is an edible basidiomycete cultivated industrially for food
      production. Different spawn and mushroom producers use genetically related A.
      bisporus strains frequently marketed as different products. In this paper we show
      that the use of suitable molecular markers reveals the high level of genetic
      homology of commercial strains of A. bisporus, and allows, at the same time, to
      distinguish between them. In the course of this work, a molecular marker
      potentially linked to the agronomic character 'mushroom weight' has been
      identified by bulked segregant analysis.

PMID- 11325553
TI  - Molecular characterization of a recombinant replication protein (Rep) from the
      Antarctic bacterium Psychrobacter sp. TA144.
AB  - The Antarctic Gram-negative bacterium Psychrobacter sp. TA144 contains two small
      cryptic plasmids, called pTAUp and pTADw. pTAUp encodes a replication enzyme
      (PsyRep) whose activity is responsible for plasmid replication via the rolling
      circle replication pathway. Several attempts to produce the wild-type
      biologically active PsyRep in Escherichia coli failed, possibly due to auto
      regulation of the protein population. However, the serendipitous occurrence of a
      frameshift mutation during the preparation of an expression vector resulted in
      the over-production of a recombinant protein, changed in its last 14 amino acid
      residues (PsyRep*), that precipitates in insoluble form. The purification of
      PsyRep* inclusion bodies and the successful refolding of the cold adapted enzyme
      allowed us to carry out its functional characterization. The mutated protein
      still displays a double stranded DNA nicking activity, while the change at the C
      terminus impairs the enzyme specificity for the pTAUp cognate Ori+ sequence.

PMID- 11325554
TI  - Addition of substrate-binding domains increases substrate-binding capacity and
      specific activity of a chitinase from Trichoderma harzianum.
AB  - Chitinase Chit42 from Trichoderma harzianum CECT 2413 is considered to play an
      important role in the biocontrol activity of this fungus against plant pathogens.
      Chit42 lacks a chitin-binding domain (ChBD). We have produced hybrid chitinases
      with stronger chitin-binding capacity by fusing to Chit42 a ChBD from Nicotiana
      tabacum ChiA chitinase and the cellulose-binding domain from cellobiohydrolase II
      of Trichoderma reesei. The chimeric chitinases had similar activities towards
      soluble substrate but higher hydrolytic activity than the native chitinase on
      high molecular mass insoluble substrates such as ground chitin or chitin-rich
      fungal cell walls.

PMID- 11325555
TI  - Analysis of mutational effects of a polyhydroxybutyrate (PHB) polymerase on
      bacterial PHB accumulation using an in vivo assay system.
AB  - Polymerase is a central enzyme involved in the biosynthesis of
      polyhydroxybutyrate (PHB), a well-known bacterial biodegradable polyester. In
      this study, we have established an in vivo assay system to analyze mutational
      effects of Ralstonia eutropha polymerase (termed PhbC(Re)) on the level of PHB
      accumulation in recombinant strains of Escherichia coli. This in vitro evolution
      system consists of a polymerase chain reaction-mediated random mutagenesis and
      two assay procedures, a plate assay using a PHB-staining dye and a high-pressure
      liquid chromatographic assay based on the converting reaction from PHB to
      crotonic acid. The distribution pattern of the PHB accumulation level of the
      mutant population using 378 clones arbitrarily selected, suggested that the
      present level of PhbC(Re) is high and well-optimized. It is noteworthy that many
      of the amino acid substitutions affecting the PHB accumulation occurred in the
      conserved positions or regions within an 'alpha/beta hydrolase fold' which is
      commonly found among hydrolytic enzymes. From a good correlation with the level
      of PHB accumulation, an activity estimation of the PhbC(Re) would be efficiently
      achieved by monitoring the level of PHB accumulation using the in vivo assay
      system established here.

PMID- 11325557
TI  - The multidomain xylanase Xyn10B as a cellulose-binding protein in Clostridium
      stercorarium.
AB  - The cells of Clostridium stercorarium F-9 grown on cellobiose bound to insoluble
      cellulose allomorphs such as phosphoric acid-swollen cellulose (ASC). Treatment
      of the cells with 3 M guanidine hydrochloride extracted surface-layer proteins
      from the cells and abolished the affinity of the cells for ASC. SDS
      polyacrylamide gel electrophoresis, zymogram, and immunological analyses
      indicated that one of the major surface layer proteins was Xyn10B, which is a
      modular xylanase comprising two family 22 carbohydrate-binding modules (CBMs), a
      family 10 catalytic domain of glycosyl hydrolases, a family 9 CBM, and two S
      layer homologous (SLH) domains. The C. stercorarium F-9 cells treated with
      guanidine hydrochloride coprecipitated with ASC upon the addition of a derivative
      of Xyn10B containing both a CBM and SLH domain in addition to a catalytic domain,
      but not a derivative without Xyn10B-SLH domains, suggesting that Xyn10B
      functioned as a cellulose-binding protein in C. stercorarium F-9.

PMID- 11325556
TI  - Characterization of FruR as a putative activator of the fructose operon of
      Spiroplasma citri.
AB  - The role of fruR, the first gene of the Spiroplasma citri fructose operon, was
      investigated. In vivo transcription of the fructose operon is greatly enhanced by
      the presence of fructose in the growth medium while glucose has no effect. When
      fruR is not expressed, transcription of the fructose operon is not stimulated by
      fructose, and fructose fermentation is decreased, indicating that FruR is an
      activator of the fructose operon. The promoter of the fructose operon was
      localized by primer extension, and a direct T-rich repeat was found to overlap
      the -35 box. This repeat could be the binding site of FruR. The presence of
      fructose in the culture medium also decreases the toxicity of methyl alpha
      glucoside, however FruR is not involved in this regulation. This is the first
      description of transcription regulation of a mollicute operon.

PMID- 11325558
TI  - Specific identification of Lactobacillus helveticus by PCR with pepC, pepN and
      htrA targeted primers.
AB  - Specific regions in three genes coding for aminopeptidases C and N, and a trypsin
      like serine protease were selected as species-specific primer sequences for rapid
      and reliable identification of Lactobacillus helveticus strains. The PCR
      procedures carried out gave specific 524-, 726- and 918-bp amplificates, with DNA
      isolated from L. helveticus. No PCR product was generated for closely related
      bacteria. The amplification products were also screened for their species
      specificity in dot blot hybridization with representatives of the most closely
      related genera and species and a number of other bacterial species.

PMID- 11325559
TI  - Inhibition of glutamate transporter by theanine enhances the therapeutic efficacy
      of doxorubicin.
AB  - Theanine, a major amino acid existing in green tea, enhanced the antitumor
      activity of doxorubicin (DOX) due to inhibition of DOX efflux from tumor cells.
      In order to clarify the mechanism, we have investigated the contribution of
      glutamate transporters to the action of theanine, because theanine is a glutamate
      analogue. In M5076 ovarian sarcoma cells, glutamate transport inhibitors reduced
      the efflux of DOX, as well as theanine. Incidentally, theanine significantly
      inhibited the glutamate uptake by M5076 cells in a concentration-dependent manner
      similar to specific inhibitors. These results suggested that the inhibition of
      DOX efflux was induced by the inhibition of glutamate transport by theanine. In
      addition, RT-PCR and Western blot analysis revealed the expression of GLAST and
      GLT-1, astrocytic high-affinity glutamate transporters, in M5076 cells. Thus,
      theanine was shown to competitively inhibit the glutamate uptake by acting on
      these glutamate transporters. This action suggested the contribution of glutamate
      transporters to the inhibition of DOX efflux by theanine. We revealed the novel
      mechanism of enhancement of the antitumor efficacy of DOX via the inhibition of
      glutamate transporters by theanine.

PMID- 11325560
TI  - An antimicrotubule agent, TZT-1027, does not induce neuropathologic alterations
      which are detected after administration of vincristine or paclitaxel in animal
      models.
AB  - One of the major dose-limiting toxicities induced by antimicrotubule antitumor
      agents such as vinca alkaloids and taxanes is peripheral neuropathy. The
      neurotoxicity of TZT-1027 (a dolastatin 10 derivative antimicrotubule agent) was
      thus assessed using the animal models for antimicrotubule agent-induced
      neurotoxicity. Rabbits were intravenously given TZT-1027 or vincristine weekly
      for 5 weeks. In the mouse study, TZT-1027, vincristine or paclitaxel was
      intravenously given every 2 days and/or weekly. Despite the neuropathologic
      evidence such as myelinated axonal and fiber degeneration in the peripheral
      nerves and in the sensory tracts of the spinal cord following the treatment with
      vincristine or paclitaxel, no drug-induced alteration was observed in the TZT
      1027 groups. Although there are reports that some other dolastatin derivatives
      with antimicrotubule activity showed no neurotoxic potential in humans, the
      present study represents the first demonstration in experimental animals that a
      dolastatin derivative has no, or at least a lower, neurotoxic potential compared
      to other antimicrotubule agents.

PMID- 11325561
TI  - Pulmonary induction of proinflammatory mediators following the rat exposure to
      benzo(a)pyrene-coated onto Fe2O3 particles.
AB  - Epidemiological evidence firmly implicated an interactive effect between Fe2O3
      and benzo(a)pyrene (B(a)P) in causing lung cancer. However, despite intensive
      investigation, the mechanism involved is not precisely established. Since the
      accumulation of reactive oxygen intermediates (ROI)-mediated damage and/or immune
      induced injury might be a possible cause of lung cancer, we studied the oxidative
      and the inflammatory effects of Fe2O3 (3 mg), B(a)P (3 mg) or B(a)P (3 mg)-coated
      onto Fe2O3 (3 mg) particles on this relevant organ target in Sprague-Dawley rats.
      We investigated lipid peroxidation (malondialdehyde; MDA) and secretion of some
      inflammatory mediators (tumor necrosis factor-alpha, TNF-alpha; interleukin-1
      beta, IL-1beta; nitric oxide, NO) in lungs. In addition, mRNA expressions of TNF
      alpha, IL-1beta and inducible nitric oxide synthase (iNOS) were evaluated. Our
      results show that exposure to Fe2O3 and B(a)P, alone or in association, induced 2
      fold increases in MDA production suggesting thereby oxidative stress conditions
      (P<0.01). Exposure to Fe2O3, B(a)P or B(a)P-coated onto Fe2O3 particles
      significantly increased both mRNA expression and/or synthesis of inflammatory
      mediators. The main findings of this work were that the association of Fe2O3 and
      B(a)P induces more pronounced induction of inflammatory mediators (IL-1beta
      secretion, P<0.01; IL-1beta mRNA expression, P<0.01; iNOS mRNA expression,
      P<0.05) than B(a)P by itself. Hence, our results may explain why concurrent
      exposure to Fe2O3 and B(a)P is more deleterious in lungs than exposure to B(a)P
      alone.

PMID- 11325562
TI  - Catalytic inhibition of DNA topoisomerase IIalpha by sodium azide.
AB  - It has been demonstrated previously that sodium azide reduces the clastogenicity
      of several DNA topoisomerase II (topo II) poisons in cultured mammalian cells.
      These studies suggested that azide may be a catalytic topo II inhibitor. Azide
      interferes with mitochondrial production of ATP and is also known to inhibit
      cellular ATPases. Since topo II requires ATP for catalytic activity (enzyme
      turnover), it seemed likely that interference with ATP levels or ATP catabolism
      was the underlying mechanism of topo II inactivation; however, this has not been
      examined in living cells under conditions where the endogenous topo II is active
      on genomic DNA. The present studies were carried out to verify that azide
      inhibits endogenous topo II in cells. We show that azide blocks both decatenation
      and relaxation activity of purified topo II in a concentration dependent manner
      and reduces topoII/DNA covalent complex formation in cells. From these studies,
      it is concluded that sodium azide catalytically inactivates topo II via an ATP
      sensitive process.

PMID- 11325563
TI  - Induction of urinary excretion of 3-nitrotyrosine, a marker of oxidative stress,
      following administration of pyridostigmine bromide, DEET (N,N-diethyl-m
      toluamide) and permethrin, alone and in combination in rats.
AB  - In this study, we determined levels of 3-nitrotyrosine in rat urine following
      administration of a single oral dose of 13 mg/kg pyridostigmine bromide (PB) (3
      dimethylaminocarbonyloxy-N-methylpyridinum bromide), a single dermal dose of 400
      mg/kg N,N-diethyl-m-toluamide (DEET) and a single dermal dose of 1.3 mg/kg
      permethrin, alone and in combination. Urine samples were collected from five
      treated and five control rats at 4, 8, 16, 24, 48, and 72 h following dosing.
      Solid-phase extraction coupled with high-performance liquid chromatography with
      ultraviolet detection at 274 nm was used for the determination of tyrosine and 3
      nitrotyrosine. A single oral dose of PB and a single dermal dose of DEET or their
      combination significantly (P<0.05) increased levels of 3-nitrotyrosine starting
      24 h after dosing compared with control urine samples. The maximum increase of 3
      nitroytyrosine was detected 48 h after combined administration of PB and DEET.
      The ratio of 3-nitrotyrosine to tyrosine in urine excreted 48 h after dosing was
      0.19+/-0.04, 0.20+/-0.05, 0.28+/-0.03, 0.32+/-0.04, 0.19+/-0.05, 0.42+/-0.04,
      0.27+/-0.03, 0.36+/-0.04, and 0.48+/-0.04 following administration of water,
      ethanol, PB, DEET, permethrin, PB+DEET, PB+permethrin, DEET+permethrin, and
      PB+DEET+permethrin, respectively. The results indicate that an oral dose of PB
      and a dermal administration of DEET, alone and in combination, could generate
      free radical species, and thus increase levels of 3-nitrotyrosine in rat urine.
      Induction of 3-nitrotyrosine, a marker of oxidative stress, following exposure to
      these compounds could be significant in understanding the proposed enhanced
      toxicity following combined exposure to these compounds.

PMID- 11325564
TI  - Effect of exposure to nitrogen dioxide on alveolar macrophage-mediated
      immunosuppressive activity in rats.
AB  - Nitrogen dioxide (NO2), a major component of air pollutants, induces inflammatory
      responses in the lungs. Resident alveolar macrophages (AM) play an
      immunosuppressive role in the lungs via suppression of lymphocyte proliferation,
      and nitric oxide (NO) plays a crucial role in this immunosuppressive activity.
      Microenvironmental changes within the alveoli during inflammatory responses,
      however, can inhibit this immunosuppressive activity of AM. The present study was
      designed to clarify the effect of NO2 exposure on the immunosuppressive activity
      of and NO production by AM in rats. Wistar rats were exposed to 10 ppm NO2 for 3,
      14 or 28 days, after which bronchoalveolar lavage fluid (BALF) was taken as a
      sample of the alveolar microenvironment. Suppression of concanavalin A-induced
      lymphocyte proliferation and NO production by AM were markedly inhibited by BALF
      from NO2-exposed rats (NO2-BALF). The inhibitory effect of NO2-BALF at 28-days
      exposure was stronger than that of NO2-BALF at 3 or 14 days exposure. In
      conclusion, AM-mediated immunosuppressive activity was inhibited by the NO2
      induced changes of the alveolar microenvironment through the inhibition of NO
      production.

PMID- 11325565
TI  - Effects of chronic morphine and N(6)-cyclopentyl-adenosine administration on
      kainic acid-induced status epilepticus.
AB  - The aim of the present study was to investigate if the upregulation of mu or A(1)
      receptors modifies the expression of the kainic acid (KA)-induced status
      epilepticus (SE). Male Wistar rats received one of the following treatments:
      saline solution (SS) (1 ml/kg, i.p. for 7 days); morphine (M) (20 mg/kg, i.p. for
      7 days) or N(6)-cyclopentyl-adenosine (CPA) (1 mg/kg, i.p. for 9 days). Twenty
      four hours after the last administration rats were sacrificed. Membranes were
      obtained mu and and A(1) receptor binding experiments were carried out.
      Furthermore, an injection of SS (1 ml/kg, i.p.) or KA (10 mg/kg, i.p.) was
      applied in rats pretreated chronically with M, CPA or SS, 48 h after the last
      administration. Seizure activity, death rate and a postictal explosive motor
      behavior were evaluated after KA administration. Chronic M administration
      increased mu receptor number in hippocampus (115%) and cortex (265%), whereas
      chronic CPA treatment enhanced A(1) receptor number in hippocampus (55%),
      amygdala (39%) and cortex (51%). The pretreatment with M facilitated the KA
      induced SE and reduced the death rate as well as the postictal explosive motor
      behavior. The pretreatment with CPA delayed the SE presentation, increased the
      death rate and decreased the postictal explosive motor behavior. These findings
      suggest that upregulation of mu receptors enhances the KA seizures, whereas
      upregulation of A(1) receptors depresses these seizures.

PMID- 11325566
TI  - Time-dependent distribution and neuronal localization of c-fos protein in the rat
      hippocampus following 4-aminopyridine seizures.
AB  - The immunohistochemical localization of c-fos protein in the CNS neurons was
      studied in a model of generalized epilepsy induced by the intraperitoneal
      injection of 4-aminopyridine to adult Wistar rats. This specific blocker of the
      voltage-dependent potassium channels proved to be suitable for use in the
      investigation of epileptogenesis. Following the treatment of adult rats with 5 mg
      kg of 4-aminopyridine, the animals experienced generalized seizures. At the end
      of the experiment, the rats were briefly anesthetized and perfused with fixative.
      Frozen coronal plane sections were cut and processed for immunohistochemistry,
      using polyclonal c-fos antibody. The number and distribution of immunostained
      cell nuclei in the hippocampus were analyzed in detail with the help of a digital
      microscope camera and a morphometry program. The highest level of immunostaining
      was detected in most of the structures at 3 h, but the level had decreased to the
      control level by 5 h following 4-aminopyridine injection. In the dentate fascia,
      immunostaining was highest at 1 h and then decreased slowly until 5 h post
      injection. The activated neuronal assemblies were analyzed with the aid of
      parvalbumin c-fos double immunostaining. These countings revealed the highest
      inhibitory interneuronal activation in every part of the hippocampus (including
      the dentate fascia) at 3 h post-injection. The results indicate that systemic 4
      aminopyridine induces limbic seizures, which are probably initiated in the
      entorhinal cortex.

PMID- 11325567
TI  - Gamma-vinyl GABA reduces paired pulse inhibition in the rat dentate gyrus in vivo
      and in vitro.
AB  - Gamma vinyl GABA (GVG), an irreversible GABA transaminase inhibitor, has
      anticonvulsant effects. GVG increases GABA levels in the brain by blocking its
      degradation, and is presumed to enhance GABAergic inhibition, however, in some
      cases it exacerbates seizures. We investigated the effects of GVG in vivo and in
      vitro on paired pulse inhibition (PPI) recorded in the rat dentate gyrus (DG)
      evoked by perforant path stimulation. At 2.5 h and 24 h after administration of
      GVG (1 g/kg, i.p.), there was a loss of PPI at both 15- and 25-ms interpulse
      intervals (IPI). Activation of presynaptic GABA(B) autoreceptors could explain
      this in vivo effect. We therefore further investigated the effects of co
      application of GVG with the GABA(B) antagonists 2-OH saclofen (saclofen) or CGP
      35348 (CGP) on PPI in hippocampal slices by in vitro study. Bath application of
      GVG (400 and 500 microM) not only resulted in a loss of perforant path evoked PPI
      at a 15-ms IPI, but produced facilitation of the second population spike relative
      to the first. Co-application of saclofen (250 microM) with GVG (500 microM)
      prevented facilitation of the second response of a paired-pulse. The facilitation
      of the second stimulation response produced by GVG (400 microM) was converted to
      inhibition by bath application of CGP 35348 (400 microM). These results suggest
      that activation of presynaptic GABA(B) receptors by increased extracellular GABA
      may be one of the contributing factors to the apparent paradoxical effect of GVG
      on PPI in the DG.

PMID- 11325568
TI  - Distribution of epileptiform discharges during nREM sleep in the CSWSS syndrome:
      relationship with sigma and delta activities.
AB  - PURPOSE: The EEG pattern of epilepsy with continuous spike-waves during slow wave
      sleep (CSWSS) is characterized by an almost continuous activation of spike-and
      slow-wave complexes during nREM sleep with a marked reduction of EEG
      abnormalities during REM sleep and the awake state. Experimental studies indicate
      that normal sleep oscillations that during nREM sleep lead to the appearance of
      spindles and delta waves on scalp EEG might develop into paroxysmal
      synchronization. Spectral analysis enables the quantitative description of the
      dynamics of delta (Delta Activity, DA, 0.5-4.5 Hz) and sigma activity (SA, 12-16
      Hz) and can be used to assess the relationship between SA, DA and epileptiform
      discharges (EDs) during sleep. METHODS: We analyzed the EDs distribution during
      sleep in five children affected by CSWSS. We used a model of the evolution of
      power of DA and SA to which the time series of EDs could be fitted. RESULTS: We
      found a high and positive correlation between EDs and SA. DA resulted negatively
      correlated with EDs. CONCLUSION: Our data suggest that neural mechanisms involved
      in the generation of sleep spindles facilitate EDs production in the CSWSS
      syndrome. Such a mechanism seems to be an age related phenomenon shared by other
      epileptic syndromes of childhood.

PMID- 11325569
TI  - The epileptic process as nonlinear deterministic dynamics in a stochastic
      environment: an evaluation on mesial temporal lobe epilepsy.
AB  - The theory of deterministic chaos addresses simple deterministic dynamics in
      which nonlinearity gives rise to complex temporal behavior. Although biological
      neuronal networks such as the brain are highly complicated, a number of studies
      provide growing evidence that nonlinear time series analysis of brain electrical
      activity in patients with epilepsy is capable of providing potentially useful
      diagnostic information. In the present study, this analysis framework was
      extended by introducing a new measure xi, designed to discriminate between
      nonlinear deterministic and linear stochastic dynamics. For the evaluation of its
      discriminative power, xi was extracted from intracranial multi-channel EEGs
      recorded during the interictal state in 25 patients with unilateral mesial
      temporal lobe epilepsy. Strong indications of nonlinear determinism were found in
      recordings from within the epileptogenic zone, while EEG signals from other sites
      mainly resembled linear stochastic dynamics. In all investigated cases, this
      differentiation allowed to retrospectively determine the side of the
      epileptogenic zone in full agreement with results of the presurgical workup.

PMID- 11325570
TI  - Neuroactive steroids and seizure susceptibility.
AB  - There is increasing clinical and experimental evidence that hormones, in
      particular sex steroid hormones, influence neuronal excitability and other brain
      functions. The term 'neuroactive steroids' has been coined for steroids that
      interact with neurotransmitter receptors. One of the best characterized actions
      of neuroactive steroids is the allosteric modulation of GABA(A)-receptor function
      via binding to a putative steroid-binding site. Since neuroactive steroids may
      interact with a variety of other membrane receptors, excitatory as well as
      inhibitory, they may have an impact on the excitability of specific brain
      regions. Neuronal excitability is enhanced by estrogen, whereas progesterone and
      its metabolites exert anticonvulsant effects. Testosterone and corticosteroids
      have less consistent effects on seizure susceptibility. Apart from these
      particular properties, neuroactive steroids may regulate gene expression via
      progesterone receptors. Based on their molecular properties, these compounds
      appear to have a promising therapeutical profile for the treatment of different
      neuropsychiatric diseases including epilepsy. This review focuses on the effects
      of neuroactive steroids on neuronal excitability and their putative impact on the
      physiology of epileptic disorders.

PMID- 11325571
TI  - Effects of retigabine on rhythmic synchronous activity of human neocortical
      slices.
AB  - The antiepileptic effects of the novel antiepileptic drug retigabine (D-23129) [N
      (2-amino-4-(4-flurobenzylamino)phenyl) carbamid acid ethyl ester] were tested in
      neocortical slice preparations (n=23) from 17 patients (age, 3-42 years) who
      underwent surgery for the treatment of intractable epilepsy. Epileptiform events
      consisted of spontaneously occurring rhythmic sharp waves, as well as of
      epileptiform field potentials (EFP) elicited by superfusion with Mg(2+)-free
      solution without or with addition of 10 micromol/l bicuculline. (1) Spontaneous
      rhythmic sharp waves (n=6), with retigabine application, the repetition rate was
      decreased down to 12-47% of initial value (10 micromol/l, n=3) after 180 min or
      suppressed completely within 12 min (50 micromol/l, n=3). (2) Low Mg(2+) EFP
      (n=9), with retigabine application, the repetition rate was decreased down to 50
      and 65% of initial value (10 micromol/l; n=2) after 180 min or suppressed
      completely after 9-55 min (10, 50 and 100 micromol/l; n=2 in each case). In one
      slice only a transient reduction of the repetition rate was seen with 10
      micromol/l retigabine. (3) Low Mg(2+) EFP with addition of bicuculline (n=8),
      with retigabine application, the repetition rate was decreased down to 12-55% of
      initial value (10 micromol/l; n=4) after 180 min or suppressed completely after 6
      30 min (50 and 100 micromol/l; n=2 in each case). The depressive effect of
      retigabine was reversible in all but one slice. The results show a clear
      antiepileptic effect of retigabine in human neocortical slices on spontaneously
      occurring rhythmic sharp waves and different types of induced seizure activity.

PMID- 11325572
TI  - Genetic and environmental factors in epilepsy: a population-based study of 11900
      Danish twin pairs.
AB  - The contribution of genetic and environmental factors to the occurrence of
      epilepsy was examined in an unselected sample of twins recruited from the
      population-based Danish Twin Registry. Information on the occurrence of epilepsy
      in both members of a twin pair was obtained from 11900 pairs whose ages ranged
      from 12 to 41 years. Concordance rates, odds ratios and tetrachoric correlations
      were used to quantify the similarity of monozygotic (MZ) and dizygotic (DZ)
      twins. The sample was stratified by sex and separated into two age cohorts for
      analysis. Significantly higher probandwise concordance rates were found for MZ
      compared with DZ twins (0.37 and 0.08, P<0.01). Odds ratios and tetrachoric
      correlation showed similar pattern. An etiological model including additive
      genetic and individual specific environmental factors provided the best overall
      fit to the data, with 70 and 88% of the liability to develop epilepsy being
      accounted for by genetic factors in the younger and older cohorts, respectively.
      Individual specific environmental factors explained the remaining 30 and 12%,
      respectively. In conclusion, this study has confirmed the substantial impact,
      which genetic factors have in the etiology of epilepsy. The heritability of
      epilepsy is high and seems to increase with age.

PMID- 11325573
TI  - Properties of the 15D and EQ-5D utility measures in a community sample of people
      with epilepsy.
AB  - To perform economic evaluation studies in epilepsy using utilities, such as cost
      utility analyses, it is necessary to have reliable and valid instruments for
      eliciting people's preferences. The objective of this study was to assess the
      reliability and validity of two multiattribute utility measures in a community
      sample of 397 people with epilepsy. We assessed the test-retest reliability of
      individual questionnaire items and aggregate scores. Additionally, construct
      validity was assessed by correlating items of the EQ-5D with items of the 15D
      health status questionnaire, and discriminant validity was assessed by comparing
      scores for known groups. The test-retest reliabilities for the individual items
      of the 15D (weighted kappa 0.59-0.90, except mobility with only 0.28) and the EQ
      5D (weighted kappa 0.49-0.86) were acceptable. For the composite utility scores
      the test-retest reliability was better (intraclass correlation coefficient 0.93
      for both 15D and the EQ-5D). Spearman's rank correlations between EQ-5D single
      item scores and corresponding 15D single item scores were high (rho 0.34-0.79)
      and generally higher than the associations between non-corresponding items. Some
      EQ-5D and 15D items discriminated well between patients according to seizure
      status, psychiatric comorbidity and working status; less well after antiepileptic
      drug use and neurologic comorbidity. Both the EQ-5D and 15D were reliable
      instruments and showed properties supporting the construct validity of both
      measures.

PMID- 11325574
TI  - Mutation analysis of the potassium chloride cotransporter KCC3 (SLC12A6) in
      rolandic and idiopathic generalized epilepsy.
AB  - Genetic predisposition plays a major role in the etiology of idiopathic
      epilepsies. The common epilepsy syndromes display a complex pattern of
      inheritance, with an unknown number of genes contributing to seizure
      susceptibility. During the last decade linkage studies have narrowed down several
      candidate regions for susceptibility loci of idiopathic epilepsies. Several lines
      of evidence point to the existence of an epilepsy susceptibility gene on
      chromosome 15q14. Evidence for linkage to this region has thus been reported for
      juvenile myoclonic epilepsy, common subtypes of idiopathic generalized epilepsy
      (IGE), in addition to the EEG trait 'centrotemporal spikes' in families with
      rolandic epilepsy. The chromosomal region 15q14 harbours several candidate genes
      that are involved in the regulation of neuronal excitability. One of the most
      promising candidate genes is the brain-expressed potassium chloride cotransporter
      KCC3, given that this class of ion transporter has been implicated in the
      regulation of neuronal chloride activity. We therefore performed a mutation
      analysis of KCC3 in the index patients of 23 IGE-families as well as of 16
      families with rolandic epilepsy which where selected by positive evidence for
      linkage to D15S165. Four novel single nucleotide exchanges (SNPs) were
      identified, none of which change the coding sequence. These results do not
      support a major role for KCC3 in the etiology of rolandic epilepsy or common
      subtypes of IGE.

PMID- 11325575
TI  - Metabolism of two new antiepileptic drugs and their principal metabolites S(+)-
      and R(-)-10,11-dihydro-10-hydroxy carbamazepine.
AB  - BIA 2-093 and BIA 2-059 are two stereoisomers under development as new
      antiepileptic drugs. They act as prodrugs for the corresponding hydroxy
      derivatives (S(+)- or R(-)-10,11-dihydro-10-hydroxy carbamazepine, respectively)
      which are known to be the active metabolites of the antiepileptic drug
      oxcarbazepine (OXC). The purpose of this study was to define the metabolic
      pathway especially in terms of stereoselectivity, and to estimate the possibility
      of racemization in humans. For in vivo studies, the rat, mouse and rabbit were
      chosen as models in order to cover a broad spectrum of metabolic activity. In
      addition, incubations with liver microsomes from these three species plus dog and
      monkey were compared to results obtained with human liver microsomes. It was
      found that both drugs were almost instantly hydrolysed to the corresponding 10
      hydroxy compounds in mice, rats and rabbits. Mice and rabbits were not able to
      oxidize the 10-hydroxy compounds to OXC in significant amounts. In the rat, BIA 2
      093 also gave origin to OXC, whereas BIA 2-059 resulted in the formation of OXC
      and the trans-diol metabolite in equal amounts. It could be shown that the rat is
      able to reduce the formed OXC in liver to S(+)-10-hydroxy metabolite, resulting
      in a loss of enantiomeric purity after treatment with BIA 2-059 rather than in
      the case of BIA 2-093. Human liver microsomes hydrolysed BIA 2-093 and BIA 2-059
      to their corresponding 10-hydroxy compounds and to OXC in a very small extent
      with BIA 2-093 only. Therefore, BIA 2-093 and BIA 2-059 seem to be preferable
      drugs over OXC since they most likely exhibit a 'cleaner' metabolism. From a
      therapeutic point of view BIA 2-059 would be less appropriate than BIA 2-093 for
      the purpose of treating epileptic patients due to its propensity to undergo
      inactivation to the trans-diol.

PMID- 11325576
TI  - Diurnal variation in pilocarpine-induced generalized tonic-clonic seizure
      activity.
AB  - The efficacy of the cholinergic agonist pilocarpine to evoke generalized seizures
      in rats was examined over the 24-h photocycle. Both seizure latency and severity
      during the 24-h period exhibited marked diurnal variation. Seizure activity
      generalized more rapidly throughout the dark phase and was often characterized by
      wild running clonus and tonic extensor convulsions. In contrast, electrographic
      seizures during the light phase were mainly associated with facial/forelimb
      clonus and rearing typical of pilocarpine-induced seizures. These data suggest
      that the sensitivity of the rodent brain to pilocarpine exhibits day-night
      variation and seizure activity induced during the dark phase may generalize via
      the brainstem.

PMID- 11325577
TI  - The vascular system. An overview of structure and function.
AB  - It is the function of the vascular system, through a complex network of arteries,
      capillaries and veins, to maintain cellular homeostasis. As research scientists
      it is necessary to understand not only some of the basic properties of the blood
      vessel itself but also how these vessels differ in cellular and physiological
      function. This review provides an overview of the basic physiological and
      pharmacological tenets of blood vessels. It also briefly describes in vivo and in
      vitro methods used in the measurement of blood flow and blood vessel function. It
      is hoped that this review will provide readers of this focussed issue of the
      Journal of Pharmacological & Toxicological Methods with an appreciation of the
      many mechanical, electrical and biochemical methodologies described within this
      issue.

PMID- 11325578
TI  - Measurement of body venous tone.
AB  - The venous system contains about 70% of the blood volume, and approximately 75%
      of the venous volume is in the small veins and venules. Veins play an active role
      in the control of cardiac output (CO) and blood pressure. Drugs that interfere
      with venous tone have profound effects on CO and blood pressure due to the large
      venous capacity. Information on body venous tone cannot be obtained from studies
      using isolated venous preparations and perfused venous beds, which lack
      modulating cardiovascular reflex mechanisms. In vivo methods used for the
      assessment of venous function in experimental animals and humans are as follows:
      the mean circulatory filling pressure (MCFP) method for the determination of body
      venous tone, constant CO reservoir technique for measuring vascular compliance
      and unstressed volume, plethysmography or blood-pool scintigraphy along with
      venous occlusion for measuring the volume and compliance of an organ, linear
      variable differential transformer (LVDT) technique for estimating the diameter of
      a human dorsal hand vein, intravascular ultrasound (IVUS) imaging technique to
      monitor the cross-sectional area of a large vein, and ultrasonic crystals to
      estimate the dimension of an organ. These methods are described and critically
      evaluated to disclose their validity, merits and limitations.

PMID- 11325579
TI  - Direct and indirect methods used to study arterial blood pressure.
AB  - A number of different approaches exist for assessing blood pressure in
      experimental animals. Here, we briefly consider the traditional indirect (rodent
      tail-cuff) and direct (saline-filled catheter) methods of blood pressure
      measurement before going on to describe our experience with blood pressure
      telemetry in rabbits, rats, and mice. Blood pressure telemetry offers the ability
      to obtain a high-fidelity recording of blood pressure continuously, for
      relatively long periods of time, in conscious, freely moving animals, without the
      limitations of restraint or anaesthesia. Since some drift in telemeter offset and
      sensitivity are inevitable, recalibration of the telemeter devices immediately
      before implantation and following explantation is essential to ensure and
      document the accuracy of the blood pressure measurements. For long-term
      implantations, verification of the calibration can be performed in vivo, at least
      in the case of large animals, such as rabbits. Telemetry devices suitable for
      small animals, such as mice, are also available now, which will facilitate the
      accurate characterization of blood pressure in transgenic animals. Telemeter
      implantation methods in mice are presently difficult, with relatively low success
      rates being reported. However, validation of new methods, such as the insertion
      of the catheter tip via the carotid artery, may make the technique more widely
      accessible in the near future.

PMID- 11325580
TI  - Methods of blood flow measurement in the arterial circulatory system.
AB  - The most commonly employed techniques for the in vivo measurement of arterial
      blood flow to individual organs involve the use of flow probes or sensors.
      Commercially available systems for the measurement of in vivo blood flow can be
      divided into two categories: ultrasonic and electromagnetic. Two types of
      ultrasonic probes are used. The first type of flow probe measures blood flow
      mediated Doppler shifts (Doppler flowmetry) in a vessel. The second type of flow
      probe measures the "transit time" required by an emitted ultrasound wave to
      traverse the vessel and are transit-time volume flow sensors. Measurement of
      blood flow in any vessel requires that the flow probe or sensor be highly
      accurate and exhibit signal linearity over the flow range in the vessel of
      interest. Moreover, additional desirable features include compact design, size,
      and weight. An additional important feature for flow probes is that they exhibit
      good biocompatability; it is imperative for the sensor to behave in an inert
      manner towards the biological system. A sensitive and reliable method to assess
      blood flow in individual organs in the body, other than by the use of
      probes/sensors, is the reference sample method that utilizes hematogeneously
      delivered microspheres. This method has been utilized to a large extend to assess
      regional blood flow in the entire body. Obviously, the purpose of measuring blood
      flow is to determine the amount of blood delivered to a given region per unit
      time (milliliters per minute) and it is desirable to achieve this goal by
      noninvasive methodologies. This, however, is not always possible. This review
      attempts to offer an overview of some of the techniques available for the
      assessment of regional blood flow in the arterial circulatory system and
      discusses advantages and disadvantages of these common techniques.

PMID- 11325581
TI  - Techniques to measure pharmacodynamics in the intact vasculature.
AB  - Techniques are described for the intravenous, close intraarterial, or
      perivascular delivery of drugs in conscious or anaesthetized animals. Examples of
      the determination of pharmacodynamic parameters such as regional blood flow,
      large artery diameter, resistance, conductance, and blood pressure are given for
      conscious rabbits and anaesthetized dog preparations. An important issue is how
      to determine the direct vascular action of an injected drug in the light of rapid
      and powerful autonomic reflex buffering effects especially in healthy conscious
      animals. The methods of measurement of drug action on the baroreceptor-heart rate
      reflex and postural adaptation (90 degrees tilt) reflex in the conscious rabbit
      are explained. Finally, the changes to large and small artery morphology are
      explored in the rabbit hindlimb following conduit femoral artery ligation to
      induce arteriogenesis and angiogenesis. This work aims to highlight approaches to
      exploring drug action in vivo, a much neglected skill in the repertoire of the
      modern cardiovascular pharmacologist.

PMID- 11325582
TI  - Techniques to study the pharmacodynamics of isolated large and small blood
      vessels.
AB  - Techniques are described for the mounting of large artery and vein ring segments
      on wire hooks in an organ bath chamber. Each vessel is set to normalised
      conditions of passive force directly determined from its circumferential length
      tension relationship. This rigorous set up follows the normalisation routine
      established by Mulvany and Halpern for small resistance arteries mounted under
      isometric conditions on a wire myograph. Techniques for electrical field
      stimulation, and simultaneous force and membrane potential (Em), are described.
      An example of electrical field stimulation is given for the unravelling of the
      role of ATP in sympathetic co-transmission in rat mesenteric small arteries.
      Other techniques described include isobaric, isotonic mounting of small vessels,
      their morphology and receptor characterisation. Examples include human buttock
      skin arteries, small coronary arteries (CAs), and vasa vasorum arteries taken at
      coronary bypass graft operations. The underlying philosophy is that every segment
      of blood vessel constituting the intact resistance bed has its own pharmacology.
      There is no 'ideal' preparation. Whether the vessel is studied under isometric,
      isotonic, or isobaric conditions, the experimentalist must be wary of the
      influence of the methodology on the pharmacodynamics. These influences may not be
      the same between normal and diseased vessels.

PMID- 11325583
TI  - Electrophysiological recording methods used in vascular biology.
AB  - Vascular tone can be regulated by drugs that alter the activities of membrane
      ionic channels located in endothelial or smooth muscle cells in the vascular
      wall. This review examines the methods that are available to investigate the
      activities and pharmacological modulation of ion channels in vascular cells. They
      range from classical sucrose-gap and sharp-microelectrode techniques for studies
      of intact vessels, to the now widely used patch-clamp techniques for voltage
      clamp recording of single-channel and macroscopic currents in isolated cells.
      Each method is described, along with examples of applications and discussion of
      potential problems and limitations.

PMID- 11325584
TI  - The nuclear protein import assay in vascular smooth muscle cells.
AB  - Nuclear protein import plays a critical role in both proliferation and apoptosis.
      Both actions are of great importance in vascular development and pathology.
      Consequently, a technique that would allow us to characterize import and identify
      novel cofactors important in modulating the process in smooth muscle cells is of
      great applicability. In this article, we describe a simple and reliable nuclear
      protein import assay that we have modified for use on aortic smooth muscle cells
      in culture. Briefly, the procedure permeabilizes the cells and analyzes the
      nuclear retention of a fluorescent import marker. Using this method, we are able
      to analyze the effect of agents on nuclear protein import. Most importantly, we
      are able to treat the cytosol, nucleus or the whole cell independently. This
      technique will allow for the identification and development of drugs to inhibit
      or stimulate the process and, potentially, to identify mechanistic insight into
      disease processes.

PMID- 11325585
TI  - Simultaneous measurement of ERK, p38, and JNK MAP kinase cascades in vascular
      smooth muscle cells.
AB  - Activation of the mitogen-activated protein kinase (MAP kinase) pathways in
      cultured porcine aortic vascular smooth muscle cells (VSMCs) was determined
      following a 5-min stimulation with endothelin-1 (ET-1), phorbol 12-myristate 13
      acetate (PMA), H2O2, or sodium arsenite. Extracellular signal-related kinase
      (ERK1/2), p38, and c-Jun N-terminal kinase (JNK1/2) MAP kinase activation was
      assessed using anti-phospho-MAPK kinase antibodies. The activation of these
      kinase cascades was also determined by resolving lysates on Mono Q using a fast
      protein liquid chromatography (FPLC) system and measuring the phosphorylation of
      specific substrates ERK1, c-Jun, and hsp27. The substrates were subsequently
      resolved from each other and the [gamma-32P]ATP in the reaction mixture by SDS
      polyacrylamide gel electrophoresis (SDS-PAGE) and the incorporation of 32P was
      quantified by phosphor imaging. This technique revealed the presence of multiple
      peaks of activity phosphorylating ERK1 (5), c-Jun (7), and hsp27 (9). Differences
      in activation revealed by the chromatographic technique suggest that, although
      equivalent levels of activation may be detected by immunoblotting, the actual
      nature of the response differed depending upon the stimulus. Each stimulus that
      activated the MAP kinase cascades did not result in equivalent 'profile' of
      activation of kinase activities. These results suggest the presence of a
      mechanism of structural organization of the MAP kinase signaling molecules
      themselves resulting in the compartmentalization of responses with respect to the
      various cellular stimuli.

PMID- 11325586
TI  - Novel endothelium-derived relaxing factors. Identification of factors and
      cellular targets.
AB  - Nitric oxide (NO), together with prostacyclin (PGI2), mediates shear stress and
      endothelium-dependent vasodilator-mediated vasorelaxation. In the presence of
      inhibition of NO synthase (NOS) with nitroarginine analogues, such as of N(w)
      nitro-L-arginine methyl ester (L-NAME) and N(w)-nitro-L-arginine (L-NNA), and
      indomethacin, to inhibit cyclooxygenase (COX) and the synthesis of PGI2, many
      blood vessels still respond with an endothelium-dependent relaxation to either
      chemical [i.e. acetylcholine (ACh)] or mechanical (shear stress) activation. This
      non-NO and non-PGI2 vasorelaxation appears to be mediated by hyperpolarization of
      the vascular smooth muscle cell (VSMC). Although NO can hyperpolarize VSMC, a
      novel mediator, the endothelium-derived hyperpolarizing factor (EDHF), which
      opens a VSMC K(+) channel(s) notably in resistance vessels, has been proposed.
      Little agreement exists as to the nature of this putative factor, but several
      candidate molecules have been proposed and evidence, notably from the
      microcirculation, suggests that endothelium-dependent hyperpolarization (EDH) may
      be mediated via low electrical resistance coupling via myoendothelial gap
      junctions. We describe a number of techniques that are being used to identify
      EDHF and present data that address the contribution of a small increase in
      extracellular K(+) as an EDHF.

PMID- 11325587
TI  - Coumarin formation in novobiocin biosynthesis: beta-hydroxylation of the
      aminoacyl enzyme tyrosyl-S-NovH by a cytochrome P450 NovI.
AB  - BACKGROUND: Coumarin group antibiotics, such as novobiocin, coumermycin A1 and
      clorobiocin, are potent inhibitors of DNA gyrase. These antibiotics have been
      isolated from various Streptomyces species and all possess a 3-amino-4-hydroxy
      coumarin moiety as their structural core. Prior labeling experiments on
      novobiocin established that the coumarin moiety was derived from L-tyrosine,
      probably via a beta-hydroxy-tyrosine (beta-OH-Tyr) intermediate. Recently the
      novobiocin gene cluster from Streptomyces spheroides was cloned and sequenced and
      allows analysis of the biosynthesis of the coumarin at the biochemical level
      using overexpressed and purified proteins. RESULTS: Two open reading frames
      (ORFs), NovH and NovI, from the novobiocin producer S. spheroides have been
      overexpressed in Escherichia coli, purified and characterized for tyrosine
      activation and oxygenation which are the initial steps in coumarin formation. The
      65 kDa NovH has two predicted domains, an adenylation (A) and a peptidyl carrier
      protein (PCP), reminiscent of non-ribosomal peptide synthetases. Purified NovH
      catalyzes L-tyrosyl-AMP formation by its A domain, can be posttranslationally
      phosphopantetheinylated on the PCP domain, and accumulates the covalent L-tyrosyl
      S-enzyme intermediate on the holo PCP domain. The second enzyme in the pathway,
      NovI, is a 45 kDa heme protein that functions as a cytochrome P450-type
      monooxygenase with specificity for the tyrosyl-S-NovH acyl enzyme. The product
      beta-OH-tyrosyl-S-NovH was detected by alkaline release and high performance
      liquid chromatography analysis of radioactive [3H]beta-OH-Tyr and by mass
      spectrometry. Also detected was 4-OH-benzaldehyde, a retro aldol breakdown
      product of beta-OH-Tyr. The amino acid released was (3R,2S)-3-OH-Tyr by
      comparison with authentic standards. CONCLUSIONS: This work establishes that NovH
      and NovI are responsible for the formation of a beta-OH-Tyr intermediate that is
      covalently tethered to NovH in novobiocin biosynthesis. Comparable A-PCP/P450
      pairs for amino acid beta-hydroxylation are found in various biosynthetic gene
      clusters, such as ORF19/ORF20 in the chloroeremomycin cluster for tyrosine,
      CumC/CumD in the coumermycin A1 cluster for tyrosine, and NikP1/NikQ in the
      nikkomycin cluster for histidine. This phenomenon of covalent docking of the
      amino acid in a kinetically stable thioester linkage prior to chemical
      modification by downstream tailoring enzymes, could represent a common strategy
      for controlling the partitioning of the amino acid for incorporation into
      secondary metabolites.

PMID- 11325588
TI  - Bivalent inhibition of human beta-tryptase.
AB  - BACKGROUND: Human beta-tryptase is a mast cell specific trypsin-like serine
      protease that is thought to play a key role in the pathogenesis of diverse
      allergic and inflammatory disorders like asthma and psoriasis. The recently
      resolved crystal structure revealed that the enzymatically active tetramer
      consists of four quasi-identical monomers. The spatial display of the four
      identical active sites represents an ideal basis for the rational design of
      bivalent inhibitors. RESULTS: Based on modeling experiments homobivalent
      inhibitors were constructed using (i) 6A,6D-dideoxy-6A,6D-diamino-beta
      cyclodextrin as a rigid template to bridge the space between the two pairs of
      identical active sites and (ii) 3-(aminomethyl)benzene as a headgroup to occupy
      the arginine/lysine specific S1 subsites. A comparative analysis of the
      inhibitory potencies of synthetic constructs that differ in size and type of the
      spacer between headgroup and template revealed that the construct contained two 3
      (aminomethyl)benzenesulfonyl-glycine groups linked to the 6A,6D-diamino groups of
      beta-cyclodextrin as an almost ideal bivalent inhibitor with a cooperativity
      factor of 1.9 vs. the ideal value of 2. The bivalent binding mode is supported by
      the inhibitor/tetramer ratio of 2:1 required for inactivation of tryptase and by
      X-ray analysis of the inhibitor/tryptase complex. CONCLUSION: The results
      obtained with the rigid cyclodextrin template underlined the importance of a
      minimal loss of conformational entropy in bivalent binding, but also showed the
      limitations imposed by such rigid core molecules in terms of optimal occupancy of
      binding sites and thus of enthalpic strains in bidentate binding modes. The main
      advantage of bivalent inhibitors is their high selectivity for the target enzyme
      that can be achieved utilizing the principle of multivalency.

PMID- 11325589
TI  - Molecular basis of Celmer's rules: role of the ketosynthase domain in
      epimerisation and demonstration that ketoreductase domains can have altered
      product specificity with unnatural substrates.
AB  - BACKGROUND: Polyketides are structurally diverse natural products with a range of
      medically useful activities. Non-aromatic bacterial polyketides are synthesised
      on modular polyketide synthase multienzymes (PKSs) in which each cycle of chain
      extension requires a different 'module' of enzymatic activities. Attempts to
      design and construct modular PKSs that synthesise specified novel polyketides
      provide a particularly stringent test of our understanding of PKS structure and
      function. RESULTS: We show that the ketoreductase (KR) domains of modules 5 and 6
      of the erythromycin PKS, housed in the multienzyme subunit DEBS3, exert an
      unexpectedly low level of stereochemical control in reducing the keto group of a
      synthetic analogue of the diketide intermediate. This led us to construct a
      hybrid triketide synthase based on DEBS3 with ketosynthase domain ketosynthase
      (KS)5 replaced by the loading module and KS1. The construct in vivo produced two
      major triketide stereoisomers, one expected and one surprising. The latter was of
      opposite configuration at three out of the four chiral centres: the branching
      alkyl centre was that produced by KS1 and, surprisingly, both hydroxyl centres
      produced by the reduction steps carried out by KR5 and KR6 respectively.
      CONCLUSIONS: These results demonstrate that the epimerising activity associated
      with module 1 of the erythromycin PKS can be conferred on module 5 merely by
      transfer of the KS1 domain. Moreover, the normally precise stereochemical control
      observed in modular PKSs is lost when KR5 and KR6 are challenged by an unfamiliar
      substrate, which is much smaller than their natural substrates. This observation
      demonstrates that the stereochemistry of ketoreduction is not necessarily
      invariant for a given KR domain and underlines the need for mechanistic
      understanding in designing genetically engineered PKSs to produce novel products.

PMID- 11325590
TI  - Potent estrogen agonists based on carborane as a hydrophobic skeletal structure.
      A new medicinal application of boron clusters.
AB  - BACKGROUND: Carboranes (dicarba-closo-dodecaboranes) are a class of carbon
      containing polyhedral boron-cluster compounds having remarkable thermal stability
      and exceptional hydrophobicity. Applications of the unique structural and
      chemical properties offered by icosahedral carboranes in boron neutron capture
      therapy have received increasing attention over the past 30 years. However, these
      features of carboranes may allow another application as a hydrophobic
      pharmacophore in biologically active molecules that interact hydrophobically with
      receptors. RESULTS: We have designed candidate estrogen-receptor-binding
      compounds having carborane as a hydrophobic skeletal structure and synthesized
      them. The most potent compound bearing a carborane cage exhibited activity at
      least 10-fold greater than that of 17beta-estradiol in the luciferase reporter
      gene assay. Estrogen receptor-alpha-binding data for the compound were consistent
      with the results of the luciferase reporter gene assay. The compound also showed
      potent in vivo effects on the recovery of uterine weight and bone loss in
      ovariectomized mice. CONCLUSION: Further development of the potent carborane
      containing estrogenic agonists described here, having a new skeletal structure
      and unique characteristics, should yield novel therapeutic agents, especially
      selective estrogen receptor modulators. Furthermore, the suitability of the
      spherical carborane cage for binding to the cavity of the estrogen receptor-alpha
      ligand-binding domain should provide a basis for a similar approach to developing
      novel ligands for other steroid receptors.

PMID- 11325591
TI  - The three-dimensional structure of human granzyme B compared to caspase-3, key
      mediators of cell death with cleavage specificity for aspartic acid in P1.
AB  - BACKGROUND: Granzyme B, one of the most abundant granzymes in cytotoxic T
      lymphocyte (CTL) granules, and members of the caspase (cysteine aspartyl
      proteinases) family have a unique cleavage specificity for aspartic acid in P1
      and play critical roles in the biochemical events that culminate in cell death.
      RESULTS: We have determined the three-dimensional structure of the complex of the
      human granzyme B with a potent tetrapeptide aldehyde inhibitor. The Asp-specific
      S1 subsite of human granzyme B is significantly larger and less charged than the
      corresponding Asp-specific site in the apoptosis-promoting caspases, and also
      larger than the corresponding subsite in rat granzyme B. CONCLUSIONS: The above
      differences account for the variation in substrate specificity among granzyme B,
      other serine proteases and the caspases, and enable the design of specific
      inhibitors that can probe the physiological functions of these proteins and the
      disease states with which they are associated.

PMID- 11325592
TI  - Possible cause of G-C-->C-G transversion mutation by guanine oxidation product,
      imidazolone.
AB  - BACKGROUND: The genome is constantly assaulted by oxidation reactions which are
      likely to be associated with oxygen metabolism, and oxidative lesions are
      generated by many types of oxidants. Such genotoxin-induced alterations in the
      genomic message have been implicated in aging and in several pathophysiological
      processes, particularly those associated with cancer. The guanine base (G) in
      genomic DNA is highly susceptible to oxidative stress due to having the lowest
      oxidation potential. Therefore, G-C-->T-A and G-C-->C-G transversion mutations
      frequently occur under oxidative conditions. One typical lesion of G is 8-oxo-7,8
      dihydro-guanine (8-oxoG), which can pair with A. This pairing may cause G-C-->T-A
      transversion mutations. Although the number of G-C-->C-G transversions is rather
      high under specific oxidation conditions such as riboflavin photosensitization,
      the molecular basis of G-C-->C-G transversions is not known. RESULTS: To
      determine which oxidative products are responsible for G-C-->C-G transversion
      mutations, we photooxidized 5'-d(AAAAAAGGAAAAAA)/5'-d(TTTTTTCCTTTTTT) using
      either riboflavin or anthraquinone (AQ) carboxylate under UV irradiation.
      Prolonged low-temperature (4 degrees C) enzymatic digestion of photoirradiated
      sample indicated that under both conditions the amount of 8-oxo-7,8-dihydro-2'
      deoxyguanosine (8-oxodG) initially increased with decreasing amounts of 2'
      deoxyguanosine (dG), then decreased with the formation of 2-amino-5-[(2-deoxy
      beta-D-erythro-pentofuranosyl)amino]-4H-imidazol-4-one (dIz), suggesting that
      nascent 8-oxoG was further oxidized to 2,5-diamino-4H-imidazol-4-one (Iz) in
      duplex DNA. Photoirradiation of an AQ-linked oligomer with a complementary strand
      containing 8-oxoG indicated that 8-oxoG residues were oxidized to Iz. These
      results indicate that Iz is formed from 8-oxoG through long-range hole migration.
      Primer extension experiments using a template containing Iz demonstrated that
      only dGTP is specifically incorporated opposite Iz suggesting that specific Iz-G
      base pairs are formed. The 'reverse' approach consisting of DNA polymerization
      using dIzTP showed that dIzTP is incorporated opposite G, further confirming the
      formation of a Iz-G base pair. CONCLUSIONS: HPLC product analysis demonstrated
      that Iz is a key oxidation product of G through 8-oxoG in DNA photosensitized
      with riboflavin or anthraquinone. Photoreaction of AQ-linked oligomer confirmed
      that Iz is formed from 8-oxoG through long-range hole migration. Two sets of
      primer extension experiments demonstrated that Iz can specifically pair with G in
      vitro. Specific Iz-G base pair formation can explain the G-C-->C-G transversion
      mutations that appear under oxidative conditions.

PMID- 11325593
TI  - Mechanistic studies on the alkyltransferase activity of serotonin N
      acetyltransferase.
AB  - BACKGROUND: Serotonin N-acetyltransferase (arylalkylamine N-acetyltransferase,
      AANAT) catalyzes the first, rate-limiting step in the biosynthesis of the
      circadian hormone melatonin (5-methoxy-N-acetyltryptamine) from serotonin. Our
      recent discovery that, in addition to catalyzing the acetyl transfer from acetyl
      coenzyme A (acetyl-CoASH) to serotonin, AANAT is also a robust catalyst for the
      alkyl transfer reaction between CoASH and N-bromoacetyltryptamine has not only
      opened up a new way to develop cell-permeable AANAT acetyltransferase inhibitors
      that are valuable in vivo tools in helping elucidate melatonin's
      (patho)physiological roles, but has also raised a question - how does AANAT
      accelerate the alkyl transfer reaction? In this study, mechanistic aspects of the
      AANAT-catalyzed alkyl transfer reaction were explored by employing CoASH and a
      series of N-haloacetyltryptamines that were also evaluated for their AANAT
      acetyltransferase inhibitory activities. RESULTS: Investigation of various N
      haloacetyltryptamine analogs showed a similar leaving group effect on the
      enzymatic and non-enzymatic reaction rates. Steady-state kinetic analyses
      demonstrated that AANAT alkyltransferase obeys a sequential, ternary complex
      mechanism, with random substrate binding. Rate versus pH profiles revealed the
      catalytic importance of an ionizable group with pK(a) of approximately 7. All
      those N-haloacetyltryptamines that serve as substrates of AANAT alkyltransferase
      are also potent (low micromolar) in vitro inhibitors against AANAT
      acetyltransferase activity. In particular, N-chloroacetyltryptamine was also
      shown to be a potent inhibitor of intracellular melatonin production in a pineal
      cell culture assay. CONCLUSIONS: This is the first detailed investigation of the
      alkyltransferase activity associated with an acetyltransferase. Our results
      indicate that AANAT does not accelerate the alkyl transfer reaction by simple
      approximation effect as previously proposed for the similar alkyl transfer
      reaction catalyzed by other acyltransferases. This study has general implications
      for developing novel inhibitors by taking advantage of the promiscuous
      alkyltransferase activity associated with several acyltransferases.

PMID- 11325594
TI  - An inhibitor of sequence-specific proteolysis that targets the substrate rather
      than the enzyme.
AB  - BACKGROUND: Traditional protease inhibitors target the active site of the enzyme.
      However, since most proteases act on multiple substrates, even the most specific
      protease inhibitors will affect the levels of a number of different proteins.
      However, if substrate-targeted inhibitors could be developed, much higher levels
      of specificity could be achieved. In theory, compounds that bind the cleavage
      site of a particular substrate could block its interaction with a protease
      without having any effect on the processing of other substrates of that protease.
      RESULTS: A model system is presented that demonstrates the feasibility of
      substrate-targeted inhibition of proteolysis. A peptide selected genetically to
      bind a 14-residue epitope that encompasses the cleavage site of human pro-IL
      1beta was shown to inhibit interleukin-converting enzyme (ICE)-mediated
      proteolysis of model substrates containing the 14-mer target sequence. However,
      the peptide had no effect on the cleavage of other ICE substrates with different
      amino acids flanking the minimal cleavage site. CONCLUSIONS: This study
      demonstrates the feasibility of substrate-targeted inhibition of proteolysis.
      More potent compounds must be developed before substrate-targeted inhibitors can
      be used routinely. Nonetheless, this novel strategy for protease inhibition seems
      promising for the development of extremely selective molecules with which to
      manipulate the maturation of many important pro-hormones, -cytokines and 
      proteins.

PMID- 11325595
TI  - Corrigendum to: "Display cloning: functional identification of natural product
      receptors using cDNA-phage display" [Chemistry & Biology 6 (1999) 707-716].

PMID- 11325596
TI  - Introduction--cytokine receptors, signaling pathways and viruses.

PMID- 11325597
TI  - The interferon system and interferon regulatory factor transcription factors --
      studies from gene knockout mice.
AB  - Interferon regulatory factors (IRFs) were initially identified as regulators of
      IFN-alpha/beta genes and to date nine members have been determined in human and
      mouse. They share a conserved DNA-binding domain in the N-terminal portion that
      recognizes similar DNA sequences. Despite their similar DNA binding specificity,
      the IRFs show diverse functions in response to extra cellular stimuli. Although
      the study of IRFs was started with respect to regulation of the IFN-alpha/beta
      gene expression, recent studies have revealed other aspects of IRF functions. In
      this review, we summarize our current knowledge of the functions of IRF family
      members revealed by our gene targeting study in mice, focusing on the regulation
      of the IFN system.

PMID- 11325598
TI  - The virus battles: IFN induction of the antiviral state and mechanisms of viral
      evasion.
AB  - Response to IFN involves a rapid and direct signal transduction mechanism that
      quickly reports that presence of extracellular cytokine to the cell nucleus,
      preserving the specificity inherent in cytokine-receptor interactions to
      transcriptionally induce expression of a set of genes encoding important
      antiviral proteins. Establishment of the resulting antiviral state provides a
      crucial initial line of defense against viral infection. Studies of IFN-deficient
      cells and animals derived by gene targeting have demonstrated the essential
      nature of IFN-mediated innate immunity. The long co-evolutionary history of
      viruses with their hosts has seen the development of a variety of evasive
      adaptations that allow viruses to circumvent or inactivate host antiviral
      mechanisms. Further understanding of both host and viral components of this
      battle may provide important new strategies for vaccine development and creation
      of novel antiviral compounds.

PMID- 11325599
TI  - Control of interferon signaling in human papillomavirus infection.
AB  - Human papillomaviruses (HPV) infect mucosal and cutaneous epithelium resulting in
      several types of pathologies, most notably, cervical cancer. Persistent infection
      with sexually transmitted oncogenic HPV types represents the major risk factor
      for the development of cervical cancer. The development of HPV-associated
      cervical cancer has been closely linked to the expression of the viral oncogenes
      E6 and E7 in the tumor cells. The major viral oncoproteins, E6 and E7, target the
      cellular tumor suppressor gene products p53 and Rb, respectively. As detailed
      within, these interactions result in the stimulation of proliferation and the
      inhibition of apoptosis, thus representing major oncogenic insults to the
      infected cell. In addition to mediating transformation, the E6 and E7 genes also
      play significant roles in altering the immune response against infected cells by
      suppressing interferon (IFN) expression and signaling. At the clinical level,
      IFNs have been used in the treatment of HPV-associated cervical intraepithelial
      neoplasia (CIN) or cervical cancers with mixed results. The success of the
      treatment is largely dependent on the subtype of HPV and the immune response of
      the patients. Despite this inefficiency, the increasing knowledge about the
      regulation of IFN signaling pathways at molecular level may hold a promise for
      the use of new therapeutic strategies against HPV infection. Studies on the
      regulation of the function of IFN-inducible gene products by the E6 and E7 may
      lead to the development of new therapeutic approaches based on strategies that
      modify the function of the HPV oncoproteins and restore IFN-signaling pathways
      through endogenous control mechanisms.

PMID- 11325600
TI  - Molecular pathogenesis of influenza A virus infection and virus-induced
      regulation of cytokine gene expression.
AB  - Despite vaccines and antiviral substances influenza still causes significant
      morbidity and mortality world wide. Better understanding of the molecular
      mechanisms of influenza virus replication, pathogenesis and host immune responses
      is required for the development of more efficient means of prevention and
      treatment of influenza. Influenza A virus, which replicates in epithelial cells
      and leukocytes, regulates host cell transcriptional and translational systems and
      activates, as well as downregulates apoptotic pathways. Influenza A virus
      infection results in the production of chemotactic (RANTES, MIP-1 alpha, MCP-1,
      MCP-3, and IP-10), pro-inflammatory (IL-1 beta, IL-6, IL-18, and TNF-alpha), and
      antiviral (IFN-alpha/beta) cytokines. Cytokine gene expression is associated with
      the activation of NF-kappa B, AP-1, STAT and IRF signal transducing molecules in
      influenza A virus-infected cells. In addition of upregulating cytokine gene
      expression, influenza A virus infection activates caspase-1 enzyme, which is
      involved in the proteolytic processing of proIL-1 beta and proIL-18 into their
      biologically active forms. Influenza A virus-induced IFN-alpha/beta is essential
      in host's antiviral defence by activating the expression of antiviral Mx, PKR and
      oligoadenylate synthetase genes. IFN-alpha/beta also prolongs T cell survival,
      upregulates IL-12 and IL-18 receptor gene expression and together with IL-18
      stimulates NK and T cell IFN-gamma production and the development of Th1-type
      immune response.

PMID- 11325601
TI  - Viral proteins and the mitochondrial apoptotic checkpoint.
AB  - Regulated cell death by apoptosis constitutes a primary host defense for
      counteracting invading viral pathogens. In recent years, advances in the field of
      apoptosis research have revealed that mitochondria and mitochondria-derived
      factors play a central role in regulating cellular commitment to apoptosis. Here
      we explore the role of viral proteins in modulating cell death pathways that are
      relayed via this mitochondrial checkpoint.

PMID- 11325602
TI  - X protein of hepatitis B virus modulates cytokine and growth factor related
      signal transduction pathways during the course of viral infections and
      hepatocarcinogenesis.
AB  - Hepatitis B virus produces chronic infections of the liver leading to cirrhosis
      and hepatocellular carcinoma. The X protein of hepatitis B virus (HBx) is a
      multifunctional protein that can interact with p53 but can also influence a
      variety of signal transduction pathways within the cell. In most instances this
      small viral protein favors cell survival and probably initiates
      hepatocarcinogenesis. HBx upregulates the activity of a number of transcription
      factors including NF-kappa B, AP-1, CREB, and TBP. However, the majority of HBx
      is localized to the cytoplasm where it interacts with and stimulates protein
      kinases such as protein kinase C, Janus kinase/STAT, IKK, PI-3-K, stress
      activated protein kinase/Jun N-terminal kinase, and protein kinase B/Akt. This
      small viral protein can localize to the mitochondrion. HBx may act as an adaptor
      or kinase activator to influence signal transduction pathways. This review will
      attempt to analyze the involvement of HBx in signal transduction pathways during
      hepatitis B viral infections and hepatocellular carcinoma development.

PMID- 11325603
TI  - Functional activities of the human T-cell leukemia virus type I Tax oncoprotein:
      cellular signaling through NF-kappa B.
AB  - Human T-cell leukemia virus type I (HTLV-I) is the etiological agent for adult T
      cell leukemia (ATL), as well as for tropical spastic paraparesis (TSP) and HTLV-I
      associate myelopathy (HAM). A biological understanding of the involvement of HTLV
      I and in ATL has focused significantly on the workings of the virally-encoded 40
      kDa phospho-oncoprotein, Tax. Tax is a transcriptional activator. Its ability to
      modulate the expression and function of many cellular genes has been reasoned to
      be a major contributory mechanism explaining HTLV-I-mediated transformation of
      cells. In activating cellular gene expression, Tax impinges upon several cellular
      signal-transduction pathways, including those for CREB/ATF and NF-kappa B. In
      this paper, we review aspects of Tax's transcriptional potential with particular
      focus on recent evidence linking Tax to IKK (I kappa B-kinase)-complex and MAP3Ks
      (mitogen-activated protein kinase kinase kinases).

PMID- 11325604
TI  - Human immunodeficiency virus type-1 and chemokines: beyond competition for common
      cellular receptors.
AB  - The chemokines and their receptors have been receiving exceptional attention in
      recent years following the discoveries that some chemokines could specifically
      block human immunodeficiency virus type 1 (HIV-1) infection and that certain
      chemokine receptors were the long-sought coreceptors which, along with CD4, are
      required for the productive entry of HIV-1 and HIV-2 isolates. Several chemokine
      receptors or orphan chemokine receptor-like molecules can support the entry of
      various viral strains, but the clinical significance of the CXCR4 and CCR5
      coreceptors appear to overshadow a critical role for any of the other coreceptors
      and all HIV-1 and HIV-2 strains best employ one or both of these coreceptors.
      Binding of the HIV-1 envelope glycoprotein gp120 subunit to CD4 and/or an
      appropriate chemokine receptor triggers conformational changes in the envelope
      glycoprotein oligomer that allow it to facilitate the fusion of the viral and
      host cell membranes. During these interactions, gp120 appears to be capable of
      inducing a variety of signaling events, all of which are still not defined in
      detail. In addition, the more recently observed dichotomous effects, of both
      inhibition and enhancement, that chemokines and their receptor signaling events
      elicit on the HIV-1 entry and replication processes has once again highlighted
      the intricate and complex balance of factors that govern the pathogenic process.
      Here, we will review and discuss these new observations summarizing the potential
      significance these processes may have in HIV-1 infection. Understanding the
      complexities and significance of the signaling processes that the chemokines and
      viral products induce may substantially enhance our understanding of HIV-1
      pathogenesis, and perhaps facilitate the discovery of new ways for the prevention
      and treatment of HIV-1 disease.

PMID- 11325605
TI  - Molecular piracy of Kaposi's sarcoma associated herpesvirus.
AB  - Kaposi's Sarcoma associated Herpesvirus (KSHV) is the most recently discovered
      human tumor virus and is associated with the pathogenesis of Kaposi's sarcoma,
      primary effusion lymphoma, and Multicentric Casttleman's disease. KSHV contains
      numerous open reading frames with striking homology to cellular genes. These
      viral gene products play a variety of roles in KSHV-associated pathogenesis by
      disrupting cellular signal transduction pathways, which include interferon
      mediated anti-viral responses, cytokine-regulated cell growth, apoptosis, and
      cell cycle control. In this review, we will attempt to cover our understanding of
      how viral proteins deregulate cellular signaling pathways, which ultimately
      contribute to the conversion of normal cells to cancerous cells.

PMID- 11325607
TI  - Oncolytic viruses and cancer therapy.

PMID- 11325606
TI  - Cytokine signaling and Epstein-Barr virus-mediated cell transformation.
AB  - Epstein-Barr virus (EBV) latent infection is tightly associated with the
      development of lymphoid and epithelial human malignancies. The disruption of cell
      growth checkpoints is mediated by a limited number of viral proteins that
      interfere with signal transduction mechanisms and transcription control in the
      infected cell. Genetic and biochemical evidence supports the notion that EBV
      mediated transformation relies extensively on interference with cytokine
      signaling networks. This is achieved through direct modulation of cytokine
      receptor signaling mechanisms as well as alterations in the expression levels of
      various cytokines. The principal effector of these interventions is the EBV
      latent membrane protein 1 (LMP1) which plays a central role in the transformation
      process. This viral protein mimics activated receptors of the tumor necrosis
      factor receptor superfamily to promote cell growth and antiapoptotic mechanisms.
      LMP1 and other EBV latent proteins upregulate cytokines and growth factors which
      participate in autocrine and paracrine loops that are likely to promote cell
      transformation and modulate immune responses. This report will review the
      molecular mechanisms that underlie the disruption of cytokine signaling
      mechanisms in EBV-mediated transformation with a particular emphasis on the LMP1
      mechanism of function.

PMID- 11325608
TI  - Characterization of mevalonate kinase V377I, a mutant implicated in defective
      isoprenoid biosynthesis and HIDS/periodic fever syndrome.
AB  - The list of diseases linked to defects in lipid metabolism has recently been
      augmented by the addition of hyperimmunoglobulinemia D and periodic fever
      syndrome (HIDS: MIM 260920), which are correlated with depressed levels of
      mevalonate kinase activity [1,2] and protein [1]. More specifically, a V377I
      substitution has been proposed to account for this disease. We observed that V377
      appears to be far from invariant in eukaryotic mevalonate kinases. Prokaryotic
      mevalonate kinases are lower in molecular weight and several terminate prior to
      residue 377 of the eukaryotic proteins. These observations prompted our direct
      test of the impact of V377 on activity and protein stability by engineering a
      V377I mutation in a recombinant human mevalonate kinase. The mutant protein has
      been isolated and kinetically characterized. In comparison with wild-type enzyme,
      V377I exhibits only modest differences (notably > or = 6-fold inflation of
      K(m(MVA))) that do not account for the diminished mevalonate kinase activity
      assayed in HIDS cell extracts. Moreover, thermal inactivation (50 degrees C) of
      isolated wild-type and V377I enzymes demonstrates little difference in stability
      between these proteins. We conclude that a single V377I substitution is unlikely
      to explain the observation of depressed mevalonate kinase stability and catalytic
      activity in HIDS.

PMID- 11325609
TI  - Two unusual glycerophospholipids from a filamentous fungus, Absidia corymbifera.
AB  - The chloroform-methanol extractable lipids of the soil filamentous fungus Absidia
      corymbifera VKMF-965 account for about 20% by weight of dry cells and are
      composed of low-polarity constituents (about 75% of the total lipids), such as
      triacylglycerols (mainly), diacylglycerols, sterols and free fatty acids, as well
      as of glycolipids (about 3%) and phospholipids. The last consist largely of
      components common to the fungal lipids, namely, phosphatidylethanolamine (38% of
      the total phospholipids), phosphatidyl-myo-inositol (16%), diphosphatidylglycerol
      (12%), phosphatidylcholine (7%), phosphatidic acid (6%) and phosphatidylglycerol
      (3%), and two unusual phospholipids, PL1 (6%) and PL2 (9%). Based on the infrared
      (IR), (1)H-nuclear magnetic resonance (NMR), (13)C-NMR and mass spectra along
      with the results of degradation experiment, these two phospholipids have been
      established to be 1,2-diacyl-sn-glycero-3-phospho(N-acetylethanolamine), or N
      acetyl phosphatidylethanolamine, and 1,2-diacyl-sn-glycero-3-phospho(N
      ethoxycarbonyl-ethanolamine), respectively. These structures have been confirmed
      by preparing similar phospholipids from the phosphatidylethanolamine isolated
      from the same fungus and correlating their chromatographic behaviour, IR and (1)H
      NMR spectra with those of PL1 and PL2. So far N-acetyl phosphatidylethanolamine
      has been detected only in cattle and human brains and a human placenta but its
      structure was not rigorously proved. PL2 is a novel lipid; to our knowledge no
      natural phospholipid with an urethane group has yet been found. The main fatty
      acids of both the phospholipids are n-hexadecanoic, octadecanoic and
      octadecadienoic ones; PL2 contains in addition a considerable amount of
      octadecatrienoic acid with its greater portion located at the sn-1 position.

PMID- 11325610
TI  - An oxidized derivative of cholesterol increases the release of soluble vascular
      cell adhesion molecule-1 from human umbilical vein endothelial cells in culture.
AB  - Treatment of human umbilical vein endothelial cells (HUVECs) with 7
      ketocholesterol resulted in an increased release of soluble vascular cell
      adhesion molecule-1 (VCAM-1) into culture medium. 7-Ketocholesterol did not
      enhance the expression of mRNA for VCAM-1. 7 beta-Hydroxy- or 25
      hydroxycholesterol had no effect on soluble VCAM-1 levels. Western blot analysis
      revealed that soluble VCAM-1, in the conditioned medium of both 7-ketocholesterol
      stimulated and control cells, had a molecular size of 100 kDa. Stimulation of the
      TNF-alpha-treated HUVECs with 7-ketocholesterol further increased the levels of
      soluble VCAM-1 in the culture medium. Again, 7-ketocholesterol did not affect the
      VCAM-1 mRNA level, which was enhanced by TNF-alpha. Pretreatment of the cells
      with tissue inhibitor of membrane metalloproteinase-2 (TIMP-2) completely
      inhibited the release of VCAM-1 in response to 7-ketocholesterol but TIMP-1 had
      no effect. Adherence of mononuclear cells to TNF-stimulated HUVEC monolayers was
      slightly inhibited by 7-ketocholesterol, but this oxysterol did not affect the
      basal adherence to non-stimulated HUVECs. Immunofluorescent staining of the cells
      confirmed diffuse perinuclear distribution of VCAM-1 in HUVECs treated with TNF
      alpha, but 7-ketocholesterol did not affect the intensity or distribution of
      immunofluorescence. We conclude that 7-ketocholesterol releases VCAM-1 from the
      endothelium probably by a proteolytic process.

PMID- 11325611
TI  - Aldehydic lipid peroxidation products derived from linoleic acid.
AB  - Lipid peroxidation (LPO) processes observed in diseases connected with
      inflammation involve mainly linoleic acid. Its primary LPO products, 9
      hydroperoxy-10,12-octadecadienoic acid (9-HPODE) and 13-hydroperoxy-9,11
      octadecadienoic acid (13-HPODE), decompose in multistep degradation reactions.
      These reactions were investigated in model studies: decomposition of either 9
      HPODE or 13-HPODE by Fe(2+) catalyzed air oxidation generates (with the exception
      of corresponding hydroxy and oxo derivatives) identical products in often nearly
      equal amounts, pointing to a common intermediate. Pairs of carbonyl compounds
      were recognized by reacting the oxidation mixtures with
      pentafluorobenzylhydroxylamine. Even if a pure lipid hydroperoxide is subjected
      to decomposition a great variety of products is generated, since primary products
      suffer further transformations. Therefore pure primarily decomposition products
      of HPODEs were exposed to stirring in air with or without addition of iron ions.
      Thus we observed that primary products containing the structural element R-CH=CH
      CH=CH-CH=O add water and then they are cleaved by retroaldol reactions. 2,4
      Decadienal is degraded in the absence of iron ions to 2-butenal, hexanal and 5
      oxodecanal. Small amounts of buten-1,4-dial were also detected. Addition of m
      chloroperbenzoic acid transforms 2,4-decadienal to 4-hydroxy-2-nonenal. 4,5-Epoxy
      2-decenal, synthetically available by treatment of 2,4-decadienal with
      dimethyldioxirane, is hydrolyzed to 4,5-dihydroxy-2-decenal.

PMID- 11325612
TI  - Localization of phosphatidylinositol 4-kinase isoenzymes in rat liver plasma
      membrane domains.
AB  - The presence of different isoenzymes of phosphatidylinositol 4-kinase in isolated
      rat liver plasma membranes and their further distribution in plasma membrane
      domains was examined. Both wortmannin-sensitive and -insensitive PtdIns 4-kinase
      activities were detected in highly purified plasma membranes obtained by aqueous
      two-phase affinity partitioning. The wortmannin-sensitive enzyme was identified
      as the 230 kDa isoform by Western blotting, whereas the 92 kDa isoform was not
      detected in plasma membranes. The apparent molecular weights of these isoforms
      were 205 and 105 kDa on SDS polyacrylamide gel electrophoresis, but approximately
      500 and 230 kDa respectively on gel filtration, suggesting that both enzymes
      either are dimers or composed of heterologous subunits. Approximately 25% of the
      total 230 kDa isoenzyme present in liver, and only ca 5% of the wortmannin
      insensitive one, was associated with the plasma membrane fraction. Plasma
      membrane domains were isolated by a combination of sucrose and Nycodenz gradient
      centrifugations. The 230 kDa isoform was identified in the blood sinusoidal
      domain, but not in the bile canalicular one, and was also found in lateral plasma
      membranes. The wortmannin-insensitive isoenzyme was present only in this latter
      material. The functional implications of this distribution of PtdIns 4-kinase
      isoenzymes in plasma membrane regions are discussed.

PMID- 11325613
TI  - Pulmonary surfactant phosphatidylcholine transport bypasses the brefeldin A
      sensitive compartment of alveolar type II cells.
AB  - Brefeldin A (BFA) causes disassembly of the Golgi apparatus and blocks protein
      transport to this organelle from the endoplasmic reticulum. However, there still
      remains considerable ambiguity regarding the involvement of the Golgi apparatus
      in glycerolipid transport pathways. We examined the effects of BFA upon the
      intracellular translocation of phosphatidylcholine in alveolar type II cells,
      that synthesize, transport, store and secrete large amounts of phospholipid for
      regulated exocytosis. BFA at concentrations as high as 10 microg/ml failed to
      alter the assembly of phosphatidylcholine into lamellar bodies, the specialized
      storage organelles for pulmonary surfactant. The same concentration of BFA was
      also ineffective at altering the secretion of newly synthesized
      phosphatidylcholine from alveolar type II cells. In contrast, concentrations of
      the drug of 2.5 microg/ml completely arrested newly synthesized lysozyme
      secretion from the same cells, indicating that BFA readily blocked protein
      transport processes in alveolar type II cells. The disassembly of the Golgi
      apparatus in alveolar type II cells following BFA treatment was also demonstrated
      by showing the redistribution of the resident Golgi protein MG-160 to the
      endoplasmic reticulum. These results indicate that intracellular transport of
      phosphatidylcholine along the secretory pathway in alveolar type II cells
      proceeds via a BFA insensitive route and does not require a functional Golgi
      apparatus.

PMID- 11325614
TI  - Structure of the human acyl-CoA:cholesterol acyltransferase-2 (ACAT-2) gene and
      its relation to dyslipidemia.
AB  - Acyl-CoA:cholesterol acyltransferase (ACAT) catalyzes cholesterol esterification
      in mammalian cells. Two isoforms of ACAT have been reported to date (ACAT-1 and
      ACAT-2). ACAT-1 is ubiquitously expressed in tissues except the intestine. In
      contrast, ACAT-2 is expressed mainly in the intestine in humans. To investigate
      the relationship between ACAT-2 and dyslipidemia, we determined the structure of
      the human ACAT-2 gene and then studied the relationship between mutations of the
      ACAT-2 gene and dyslipidemia. To isolate human ACAT-2 genomic DNA, we designed
      primers based on the human ACAT-2 cDNA sequence: forward primer 5'
      ACACCTCGATCTTGGTCCTGCCATA-3' and reverse primer 5'-GGAATGCAGACAGGGAGTCCT-3'.
      Using these primers, a human P1-derived artificial chromosome (PAC) library was
      screened by PCR-based procedures. Isolated PAC clones were completely digested
      with BamHI and subcloned into plasmid vector. Subclones that contained exons were
      screened by dot-blot hybridization using partial ACAT-2 cDNA fragments. The
      coding region of the ACAT-2 gene was encoded in 15 exons from 51 to 265 base
      pairs on a 21 kilobase span of genomic DNA. The exonic sequences coincided
      completely with that of ACAT-2 cDNA, and each exon-intron junction conserved
      splicing consensus sequences. Next, 187 (91 dyslipidemic and 96 normolipidemic)
      subjects were screened by PCR single-strand conformational polymorphism analysis
      of the ACAT-2 gene. Three mutations were identified by DNA sequencing: two
      missense mutations (E14G in exon 1 and T254I in exon 7) and a point mutation in
      intron 7 (-35G-->A). Mutations in exon 1 and intron 7 were not associated with
      plasma concentrations of lipids and apolipoproteins (apo). However, plasma apoC
      III levels in T254I heterozygotes were significantly higher than those in
      subjects without mutation. Plasma triglyceride (TG) levels in T254I heterozygotes
      were similar to those in subjects without mutation. Although further studies are
      needed, our data suggest that ACAT-2 may contribute to apoC-III gene expression
      and the assembly of apoC-III and TG, possibly in the intestine.

PMID- 11325615
TI  - Glucocorticoid enhances the response of type II cells from newborn rats to
      surfactant secretagogues.
AB  - There is a developmental increase in agonist-induced surfactant secretion in type
      II cells. The response to the P2Y(2) agonist UTP is negligible in early newborn
      cells but increases with age. The response to terbutaline, N
      ethylcarboxyamidoadenosine (NECA), and ATP also increases with age. As
      glucocorticoids are known to accelerate several aspects of lung maturation we
      examined the effect of dexamethasone (Dex) on the response of 1-day-old rat type
      II cells to surfactant secretagogues. Freshly isolated cells were cultured +/-10(
      6) M Dex for 18--20 h after which phosphatidylcholine secretion was measured. Dex
      slightly decreased the basal secretion rate. However, it significantly increased
      the response to terbutaline, NECA, ATP and UTP. This effect was dependent on Dex
      concentration (EC(50)=2-6 x 10(-9) M) and blocked by the glucocorticoid receptor
      antagonist RU-486. It is unlikely to be due to increased receptor content as Dex
      had no effect on adenylate cyclase, phospholipase C or phospholipase D activation
      and the response to cAMP, forskolin and phorbol ester, secretagogues acting
      downstream from receptors, was also increased by Dex. These data show that Dex
      acts directly on the type II cell to enhance the response to surfactant
      secretagogues, that the effect of the hormone is mediated by the glucocorticoid
      receptor and suggest induction of a common downstream signaling step(s).
      Regulation of surfactant secretion may be an important function of
      glucocorticoids in the developing lung.

PMID- 11325616
TI  - Functional similarities of human and chicken apolipoprotein A-I: dependence on
      secondary and tertiary rather than primary structure.
AB  - To investigate the sequence requirements for apolipoprotein (apo) AI functions,
      comparisons of human and chicken apoAI were performed. In lipid binding assays,
      chicken apoAI was capable of transforming phospholipid vesicles into discoidal
      bilayer structures, similar in both size and apolipoprotein content to those
      produced with human apoAI under the same conditions. Human and chicken apoAI were
      indistinguishable in their relative abilities to prevent phospholipase C-induced
      aggregation of human low density lipoprotein. This activity, which is dependent
      upon formation of a stable interaction with the modified lipoprotein, represents
      a sensitive measure of apolipoprotein association with spherical lipoprotein
      particles. The ability of chicken versus human apoAI to mobilize the regulatory
      pool of cholesterol available for esterification by acyl-CoA:cholesterol
      acyltransferase by human fibroblasts was also assessed. Lipid-free chicken and
      human apoAI were equivalent in their ability to deplete cholesterol from this
      pool, as were intact chicken high density lipoprotein (HDL) and human HDL(3).
      Based on the overall sequence identity of chicken and human apoAI (48%), and
      comparison of regions thought to be responsible for key apoAI functions, these
      data indicate that amphipathic alpha-helical structure, rather than specific
      amino acid sequence, is the major determinant of apoAI lipid binding and ability
      to mobilize the regulatory pool of cellular cholesterol.

PMID- 11325617
TI  - Genome mining for human cancer genes: wherefore art thou?
AB  - In an initial data-mining effort, the draft human genome was searched to find
      paralogs of known tumor suppressor genes, and for gene arrangements, which are
      typical of oncogenes, in cancer cells. The results were disappointing, indicating
      that although knowledge of the human genome will undoubtedly be of great help,
      other approaches to identify new oncogenes are needed.

PMID- 11325618
TI  - Can modulation of endothelial nitric oxide synthase explain the vasculoprotective
      actions of statins?
AB  - Statin-based drugs are the mainstay of therapy for coronary artery disease.
      Recent insights into the cellular mechanisms of this class of drugs suggest that
      modulation of nitric oxide synthesis contributes to their beneficial actions.
      These effects are independent of their lipid-lowering effects and result in
      enhanced nitric oxide release.

PMID- 11325631
TI  - Clinical application of pharmacogenetics.
AB  - Pharmacogenetics encompasses the involvement of genes in an individual's response
      to drugs. As such, the field covers a vast area including basic drug discovery
      research, the genetic basis of pharmacokinetics and pharmacodynamics, new drug
      development, patient genetic testing and clinical patient management. Ultimately,
      the goal of pharmacogenetics is to predict a patient's genetic response to a
      specific drug as a means of delivering the best possible medical treatment. By
      predicting the drug response of an individual, it will be possible to increase
      the success of therapies and reduce the incidence of adverse side effects.

PMID- 11325619
TI  - No longer a molecular black box--new clues to apoptosis and drug resistance in
      melanoma.
AB  - Disseminated melanoma is a radiation- and chemotherapy-refractory neoplasm for
      which no standard therapy currently exists. So far, genetic and molecular studies
      have revealed few non-random chromosomal abnormalities and infrequent mutational
      spectra. Consequently, the precise molecular determinants responsible for
      melanoma progression are yet to be delineated. Recent studies, however, have
      identified defects at multiple levels of the apoptosis program in melanoma, which
      provided new clues to drug resistance of this highly aggressive neoplasm. The
      process of apoptosis provides a conceptual framework to link melanoma genetics
      with the outcome of melanoma therapy. Hence, the genes and proteins that control
      apoptosis provide exciting new targets for rationally designed anti-melanoma
      therapeutic strategies.

PMID- 11325632
TI  - Molecular regulation of eating behavior: new insights and prospects for
      therapeutic strategies.
AB  - Obesity is highly prevalent in industralized countries and is increasing
      worldwide. It is also a major risk factor for type 2 diabetes, hypertension,
      coronary artery disease and certain cancers. An understanding of the regulation
      of eating behavior is pertinent to obesity, as the latter results from an
      imbalance between food consumption and energy expenditure. Leptin and other
      hormones regulate feeding and energy balance by modulating the expression of
      neuropeptides in the brain. Major efforts are underway to determine whether the
      peripheral and central pathways involved in the regulation of feeding behavior
      and energy balance could be targeted for the treatment of obesity.

PMID- 11325633
TI  - A crucial role for CD44 in inflammation.
AB  - Current therapies for chronic inflammatory diseases typically act through the
      nonspecific downregulation of immune cell activation. However, it is becoming
      increasingly evident that parenchymal cells are also active participants in the
      inflammatory process. Future prospects for the treatment of inflammation should
      therefore include the targeting of specific inflammatory pathways in both immune
      cells and parenchymal cells. CD44, a cell-adhesion molecule that is ubiquitously
      expressed on leukocytes and parenchymal cells, has been implicated, together with
      its ligand hyaluronan (HA), in several inflammatory diseases. The mechanisms of
      action of CD44-HA interactions in inflammation might provide potential targets
      for therapy.

PMID- 11325634
TI  - Ribozyme gene therapy: applications for molecular medicine.
AB  - RNA enzymes--ribozymes--are being developed as treatments for a variety of
      diseases ranging from inborn metabolic disorders to viral infections and acquired
      diseases such as cancer. Ribozymes can be used both to downregulate and to repair
      pathogenic genes. In some instances, short-term exogenous delivery of stabilized
      RNA is desirable, but many treatments will require viral-mediated delivery to
      provide long-term expression of the therapeutic catalyst. Current gene therapy
      applications employ variations on naturally occurring ribozymes, but in vitro
      selection has provided new RNA and DNA catalysts, and research on trans-splicing
      and RNase P has suggested ways to harness the endogenous ribozymes of the cell
      for therapeutic purposes.

PMID- 11325635
TI  - The impact of the Human Genome Project on medical genetics.
AB  - The near completion of the Human Genome Project stands as a remarkable
      achievement, with enormous implications for both science and society. For
      scientists, it is the first step in a complex process that will lead to important
      advances in the diagnosis and treatment of many diseases. Society, meanwhile,
      must prevent genetic discrimination, and protect genetic privacy through
      appropriate legislation.

PMID- 11325636
TI  - Immunoablation followed or not by hematopoietic stem cells as an intense therapy
      for severe autoimmune diseases. New perspectives, new problems.

PMID- 11325637
TI  - The platelet ADP receptors.

PMID- 11325638
TI  - Historical overview of the role of platelets in hemostasis and thrombosis.
AB  - Platelets were discovered by G. Bizzozero in 1882 and rediscovered in the 1960s
      after many decades of oblivion. Interestingly enough, their role was initially
      more clearly associated with thrombosis than with hemostasis. For many years a
      serious unresolved problem was that the clotting time was normal even in severe
      thrombocytopenia. The concept of coagulation as an enzymatic cascade had not yet
      been elaborated. During the 1960s, the interest of many experts moved from the
      interaction of platelets with the process of blood coagulation to the interaction
      of these cells with the vascular wall (adhesion) and each other (aggregation).
      The discovery of the role of ADP as the principle of platelet aggregation stimuli
      was rapidly followed by other important discoveries such as the aggregating
      properties of collagen and thrombin, the release reaction, the metabolism of
      arachidonic acid, and the inhibitory effect of aspirin. The use of aspirin as a
      potential antithrombotic drug has made the history of clinical trials in the last
      30 years. The last two decades have been characterized by an explosion of cell
      and molecular biology approaches. There are presently people who study platelet
      signal transduction or platelet-leukocyte interactions but who know almost
      nothing about hemostasis or thrombosis! This is due not only to the intrinsic
      limitations of the biological approach but also to the progressive recognition of
      the role of platelets in other physiopathologic and clinical conditions such as
      inflammation, cancer growth and dissemination, and organ transplant rejection.
      Overlooked for more than two centuries after the microscope was made available to
      hematologists, considered as an artifact or a Cinderella, the platelet has mainly
      been considered in the past 30 years as a dangerous cell to be inhibited by (ever
      more expensive) drugs. But the taming of the shrew is far from being achieved.

PMID- 11325639
TI  - Distribution of fetal and embryonic hemoglobins in fetal erythroblasts enriched
      from maternal blood.
AB  - BACKGROUND AND OBJECTIVES: To determine the distribution of embryonic and fetal
      hemoglobin chains in fetal erythroblasts isolated from maternal blood in the
      first trimester of pregnancy and establish the feasibility of using these chains
      as markers for fetal cell identification. DESIGN AND METHODS: Maternal blood was
      obtained from 187 singleton pregnancies at 11-14 weeks of gestation immediately
      before fetal karyotyping by chorionic villus sampling. In all cases included in
      this study the fetal karyotype was normal. Fetal erythroblasts were isolated
      using triple density gradient separation and anti-CD71 magnetic cell sorting
      techniques. The enriched erythroblasts were stained with Kleihauer-Giemsa and
      with fluorescent antibodies for the zeta (z), epsilon (e) and gamma (g) globin
      chains. The percentage of fetal cells positive for each stain was calculated.
      Fluorescent in situ hybridization (FISH) for X and Y chromosomes was also
      performed. Comparison was made with the percentage of cells with positive Y
      signal FISH in pregnancies with male fetuses. RESULTS: The percentage of fetal
      erythroblasts stained positive was 37% for the z and 95% for both e and g globin
      chains, as well as the Kleihauer-Giemsa staining. There was a significant
      association between the Kleihauer-Giemsa stained cells and those stained with e
      and g globin chains. There was also an association between cells with Y-signals
      and those stained with e and g globin chains. INTERPRETATION AND CONCLUSIONS:
      Embryonic hemoglobin chains can be detected in the enriched fetal erythroblasts,
      with higher percentages of the e rather than the z globin chains. These chains
      are therefore potentially unique markers to be used in the identification of
      cells of fetal origin from maternal blood for prenatal diagnosis of genetic and
      chromosomal abnormalities.

PMID- 11325640
TI  - Erythroid marrow activity and functional anemia in patients with the rare
      interaction of a single functional a-globin and beta-globin gene.
AB  - BACKGROUND AND OBJECTIVES: The degree of globin chain imbalance and tissue
      hypoxia are important determinants of clinical severity in thalassemia syndromes.
      Thus phenotypic expression may be modified by interaction of alpha- and beta
      thalassemia defects, level and type of hemoglobin synthesized and oxygen release
      to the tissues. We evaluated hematology, erythroid marrow activity and functional
      anemia in patients with the rare interaction of a single a-globin gene and
      heterozygous beta-thalassemia (HbH/beta-thal trait). DESIGN AND METHODS: In 7
      patients characterized by DNA analysis to have HbH disease genotypes with beta
      thalassemia trait, we assessed hematologic findings, serum transferrin receptor
      (sTfR), serum erythropoietin (Epo), red cell 2,3-disphosphoglycerate (2,3-DPG)
      and whole blood oxygen releasing capability. RESULTS: Patients with HbH/beta-thal
      trait had moderate anemia, marked hypochromasia and microcytosis, normal or
      raised HbA2, and no electrophoretically/chromatographically detectable HbH. Epo
      and sTfR levels were significantly higher than in beta-thalassemia heterozygotes,
      but lower than in patients with HbH disease; 2,3-DPG levels were highest in
      HbH/beta-thal trait. Oxygen binding studies and simulations showed reduced oxygen
      affinity (P50) in HbH/beta-thal trait, resulting in increased oxygen release
      (O2R). INTERPRETATION AND CONCLUSIONS: Hematologic findings and bone marrow
      activity in patients with HbH/b-thal trait were consistent with the modified
      globin chain imbalance and hemoglobin synthesis expected from interaction of HbH
      disease with heterozygous b-thalassemia, although this rare complex genotype may
      elude diagnosis based on hematology alone. Significantly higher red cell 2,3-DPG
      levels were an unexpected finding, and the consequent increase in oxygen release
      capability resulted in a compensated functional anemia relative to hemoglobin
      levels.

PMID- 11325641
TI  - The value of bone marrow histology in differentiating between early stage
      Polycythemia vera and secondary (reactive) Polycythemias.
AB  - BACKGROUND AND OBJECTIVES: The diagnostic criteria of the Polycythemia Vera Study
      Group (PVSG), although generally acknowledged as the gold standard for
      establishing a diagnosis of polycythemia vera (PV), do not consider bone marrow
      features. It may, therefore, be speculated that initial-early stages of PV are
      overlooked. In this retrospective study we tried to investigate whether bone
      marrow morphology of patients with an only borderline to slight increase in
      hemoglobin/hematocrit not conforming with the postulates of the PVSG enabled a
      clear-cut differentiation between PV and secondary (reactive) polycythemias (SP).
      DESIGN AND METHODS: From a series of 348 patients with a borderline to pronounced
      erythrocytosis and representative pre-treatment bone marrow trephine biopsies a
      cohort of 86 cases was selected showing only a borderline increase in hemoglobin
      (males < 18.5 g/dL, females < 16.5 g/dL). Biopsies and clinical records were
      evaluated independently and following histologic and clinical work-up a
      straightforward consensus was reached. The diagnostic impact of histologic
      findings was tested by means of discriminate analysis of 20 standardized
      morphologic features based on histochemical and immunohistochemical staining
      techniques. RESULTS: Bone marrow histopathology in 47 patients diagnosed as
      having SP was characterized by a minimal to slight increase in cellularity with
      predominance of the erythroid lineage. Neutrophil granulocytopoiesis was
      prominent and left-shifted and small to medium-sized megakaryocytes without
      maturation defects were scattered throughout the bone marrow. There was an
      increased number of eosinophils, marked perivascular plasmacytosis, histiocytic
      reticular cells with accumulated cell debris and many iron-laden macrophages.
      Contrasting this appearance in SP our 39 patients with initial-early stage PV
      revealed a hypercellular bone marrow with trilineage proliferation (pan-myelosis)
      showing confluent sheets of erythropoiesis and loose clusters of megakaryocytes.
      Megakaryocytopoiesis was characterized by a pleomorphous appearance, i.e. giant
      cells were lying adjacent to small ones, but lacked an obvious cytologic
      abnormality. There was usually no prominent inflammatory reaction of the
      interstitial compartment. In ten patients lymphoid nodules were found, but no
      conspicuous iron deposits and in six patients a borderline to minimal increase in
      reticulin fibers was present. Following stepwise discriminate analysis of
      histologic features a set of parameters emerged including increase in
      megakaryocyte size, perivascular plasma cells, overall bone marrow cellularity
      and cellular debris. This pattern exerted a significant impact on separation
      (Wilks' lambda statistics = 0.110, p < 0.0001) of early stage PV from SP. Most
      patients with SP had an underlying bronchopulmonary condition, frequently
      associated with heavy smoking or rarely renal pathology. In addition to the
      histopathologic features, splenomegaly, thrombocyte count, LDH, LAP and
      erythropoietin levels proved to be different in the two groups of patients.
      INTERPRETATION AND CONCLUSIONS: Initial-early PV is characterized by a specific
      pattern of bone marrow histopathology. Clinical features of distinctive impact
      include splenomegaly, thrombocyte count, LDH, LAP and in particular
      erythropoietin level. Taking these clinical and histologic findings into
      consideration, reactive-secondary causes of polycythemia (SP) are clearly
      distinguishable from autonomous ones (PV).

PMID- 11325642
TI  - Multilineage involvement in the 5q- syndrome: a fluorescent in situ hybridization
      study on bone marrow smears.
AB  - BACKGROUND AND OBJECTIVES: A pluripotent progenitor cell was demonstrated to be
      involved in myelodysplastic syndromes (MDS) with normal karyotype or with
      numerical chromosome aberrations, but the pattern of lineage involvement by the
      5q31 deletion in the 5q- syndrome is unknown. We performed this study in order to
      define the distribution pattern of the 5q- anomaly better in the non-lymphoid
      cell compartment DESIGN AND METHODS: Bone marrow (BM) smears from 8 patients with
      the 5q- syndrome were studied by a modification of the fluorescent in situ
      hybridization (FISH) technique that allowed direct visualization of cell
      morphology. A commercial LSI EGR1 probe (Vysis Inc.) for the 5q31 band was used
      simultaneously in dual-color experiments with a chromosome-5-centromeric probe
      (Vysis Inc.) on BM smears from 8 patients with the 5q-syndrome. As additional
      internal controls a chromosome-7-centromeric probe and a 7q31 probe were used. To
      establish the sensitivity limit of this approach 5 normal BM smears were studied.
      All 8 patients had the 5q- chromosome as the sole anomaly in 45% to 75% of the
      interphase cells. RESULTS: For each patient 20-40 erythroblasts were analyzed:
      they were mostly proerythroblasts and basophilic erythroblasts. In all patients a
      clone carrying the 5q31 deletion was detected (35-50% of the cells, median 45%).
      Between 20-50 granulocyte precursors were scored; the 5q31 deletion was found in
      40%-50% (median 45%) in all cases. The proportion of neutrophils carrying the 5q
      deletion was consistently lower than the corresponding value in promyelocytes
      (28.7% vs 45.6%). In the 20-25 megakaryocytes analyzable in all patients, the
      overall incidence of 5q31 deletion was 52-68%. Equal proportions of large
      multilobular megakaryocytes and hypolobular megakaryocytes characteristic of the
      5q- syndrome were scored: the latter cells showed the 5q31 deletion more
      frequently than the former cells (93.6% vs 19.3% of the cells). In 66% to 100% of
      the cases (median 83%) a few cells with uncondensed nuclear chromatin pattern,
      and two or three prominent nucleoli with cytoplasmatic hypogranulation were seen
      in each sample carrying the 5q31 deletion. INTERPRETATION AND CONCLUSIONS: We
      arrived at the following conclusions: i) the transformation in the 5q- syndrome
      involves an early progenitor cell retaining the ability to proceed along multiple
      differentiation pathways; ii) there is a preferential distribution of the 5q31
      deletion within immature cells and morphologically abnormal megakaryocytes.

PMID- 11325643
TI  - Rapid detection of clonality in patients with acute lymphoblastic leukemia.
AB  - BACKGROUND AND OBJECTIVES: Polymerase chain reaction (PCR) detection of clonal T
      cell receptor (TCR) gamma and delta gene rearrangements is widely used in
      clonality assessment of lymphoid leukemias and lymphomas and for detection of
      minimal residual disease of acute lymphoblastic leukemia (ALL). Standard analyses
      for clonality assessment include Southern blotting or PCR-based detection of
      clonal TCR gene rearrangements. The latter consist of heteroduplex PCR analysis
      by separation of PCR products on non-denaturing polyacrylamide gel (PAGE). We
      describe a rapid and sensitive method to identify specific clonal rearrangements
      in PCR fragments obtained by amplification of TCRgamma and TCRdelta genes. DESIGN
      AND METHODS: We applied a semi-automated electrophoretic technique (PhastSystem ,
      Amersham Pharmacia Biotech) and compared it with standard homo-heteroduplex
      analysis in 21 cases of childhood acute lymphoblastic leukemia (ALL). RESULTS:
      The results obtained for each sample analyzed by standard homo-heteroduplex
      detection were completely reproduced by the PhastSystem approach. INTERPRETATION
      AND CONCLUSIONS: We conclude that heteroduplex analysis of TCR gene
      rearrangements using the semi-automated PhastSystem is a simple, rapid, cheap and
      highly reproducible method which can be used as an alternative to traditional
      analysis for detection of clonality.

PMID- 11325644
TI  - Telomerase activity in relation to pro- and anti-apoptotic protein expression in
      high grade non-Hodgkin's lymphomas.
AB  - BACKGROUND AND OBJECTIVES: Telomerase activity (TA) is determined by the
      catalytic unit telomerase reverse transcriptase (hTERT). In vitro studies show
      that hTERT is downregulated by wild type p53 and TA is upregulated by BCL-2
      expression. The aim of this study was to investigate the relationship of TA and
      mRNA expression of hTERT, telomerase RNA (hTER) and Tankyrase in 31 samples from
      patients with high-grade non-Hodgkin's lymphoma (HG-NHL). The results were then
      related to apoptosis and proliferation and the expression of p53 and BCL-2 family
      member proteins. DESIGN AND METHODS: The telomeric repeat amplification protocol
      (TRAP) assay and reverse transcription-polymerase chain reaction (RT-PCR) were
      used to quantify TA, and hTERT, hTER and Tankyrase mRNA expression. Proliferation
      (Ki67), p53, BCL-2, MCL-1, BAX and BAK protein expression were evaluated by
      immunohistochemistry. Apoptosis was evaluated by TUNEL staining. RESULTS: TA was
      detected in 93% of HG-NHL and tended to be higher in p53+ lymphomas. A positive
      correlation existed between mRNA expression of hTERT, hTER and Tankyrase. hTERT
      mRNA expression tended to be higher with increasing levels of apoptosis and
      proliferation, in HG-NHL samples lacking BAX expression and in samples from
      patients with survival shorter than 3.5 years. hTER mRNA expression was
      significantly higher in BAX and BAK negative samples. INTERPRETATION AND
      CONCLUSIONS: Telomerase is activated or upregulated in the majority of HG-NHL.
      Enhanced TA combined with deregulation of the factors responsible for cell
      survival and proliferation may contribute to the development and progression of
      lymphomas. Observation that high hTERT mRNA expression may be related to shorter
      survival should prompt further investigation of the clinical significance of TA
      and its components in HG-NHL.

PMID- 11325645
TI  - Biochemical markers of bone disease in asymptomatic early stage multiple myeloma.
      A study on their role in identifying high risk patients.
AB  - BACKGROUND AND OBJECTIVES: Skeletal involvement is typical of multiple myeloma
      (MM) and its occurrence increases with the progression of the disease. We
      performed a study to evaluate the clinical importance of osteocalcin (bone gla
      protein, BGP) and bone alkaline phosphatase (b-AP) as indices of osteoblastic
      activity, and deoxypyridoline (DPD) as a marker of bone resorption. DESIGN AND
      METHODS: Fifty-two MM patients, 39 patients with monoclonal gammopathy of
      undetermined significance (MGUS), and 30 normal controls entered the study. Of
      the 52 MM patients, 10 showed lytic lesions at standard X-rays and 42 did not; 21
      were untreated and 31 had been treated with chemotherapy (combined with
      bisphophonates in 15). Of these last, 12 had progressive disease and 19 were in
      plateau phase. RESULTS: DPD levels were higher in MM patients than in patients
      with MGUS or healthy controls (p = 0.0001 and p = 0.0008, respectively). No
      statistical differences were seen between patients with MGUS and healthy
      controls. BGP serum levels were significantly lower in MM patients than in MGUS
      patients (p = 0.001) or healthy controls (p = 0.001). b-AP was significantly
      higher in MGUS patients than in MM patients (p = 0.04). Biochemical parameters
      were analyzed in a continuous fashion and after dichotomization into low and high
      values with respect to normal ones. Abnormal high values of DPD showed
      statistically significant correlations with presence of osteolysis (p = 0.008),
      advanced stage (p = 0.03) and abnormal beta2-microglobulin (beta2M) values (p =
      0.03), while DPD as a continuous variable correlated significantly only with the
      presence of osteolysis (p = 0.02). In contrast, neither BGP nor b-AP showed
      statistical correlations with the presence of lytic lesions, or with other
      clinical or laboratory parameters. In 15 patients followed with serial controls,
      modifications of DPD levels reflected bone disease status well. Of the 42
      patients without radiologic evidence of skeletal lesions, 15 had abnormal DPD
      values. Spinal magnetic resonance imaging (MRI) showed initial lytic lesions in
      10 of them. INTERPRETATION AND CONCLUSIONS: Biochemical markers of bone
      metabolism are useful in evaluating and monitoring skeletal involvement in MM
      patients. They may help clinicians to identify: 1) from among patients without
      radiologic evidence of lytic lesions, those who deserve more accurate radiologic
      examinations (namely MRI); 2) from among asymptomatic patients, and in
      association with spinal MRI, those patients at higher risk of progression who
      might benefit from early treatment.

PMID- 11325646
TI  - Low-dose thalidomide plus dexamethasone is an effective salvage therapy for
      advanced myeloma.
AB  - BACKGROUND AND OBJECTIVES: The immunomodulatory drug thalidomide can inhibit
      angiogenesis and induce apoptosis in experimental models. It can also induce
      marked and durable response in advanced myeloma patients. Thalidomide has been
      used at doses ranging from 200 to 800 mg with significant toxicity. No data are
      available on the impact of low-dose thalidomide plus dexamethasone as salvage
      therapy for relapsed patients. DESIGN AND METHODS: To address this issue, myeloma
      patients were treated with 100 mg/day thalidomide continuously and dexamethasone
      40 mg, days 1-4, every month. Between June 1999 and August 2000, 77 patients
      (median age 65 years) who had relapsed or were refractory to chemotherapy were
      treated with thalidomide plus dexamethasone. RESULTS: After a minimum of 3 months
      of treatment, 14 patients (18%) showed a myeloma protein reduction of 75%-100%,
      18 patients (23%) showed a response of 50-75%, 19 patients (25%) a response of 25
      50% and 26 patients (34%) a response of < 25% or disease progression. After a
      median follow-up of 8 months, median progression-free survival was 12 months.
      Thalidomide was well tolerated. Constipation (12%) and sedation (6%) were mild.
      Tingling or numbness were present in 17% of patients, discontinuation of
      treatment was required in 10% of patients. INTERPRETATION AND CONCLUSIONS: The
      association of low-dose thalidomide plus dexamethasone is active against advanced
      myeloma. A significant proportion of patients benefit from this treatment as a
      salvage therapy postponing the delivery of chemotherapy.

PMID- 11325647
TI  - Thalidomide treatment of resistant or relapsed multiple myeloma patients.
AB  - BACKGROUND AND OBJECTIVES: Thalidomide is currently used as a very promising drug
      in patients with recurrent multiple myeloma or those refractory to chemotherapy.
      Literature data show prolonged survival in patients with advanced multiple
      myeloma treated with thalidomide but the optimal time and dose of thalidomide
      treatment remain to be established. DESIGN AND METHODS: We have treated 53
      refractory or relapsed myeloma patients with thalidomide (Grunenthal, Aachen).
      The patients received thalidomide orally as monotherapy at a starting dose of 200
      mg daily, with a dose increase of 100 mg every week to a maximum well-tolerated
      dose of 400 mg. All the patients qualified for the therapy underwent clinical and
      laboratory assessments every 4 weeks. Laboratory tests included complete blood
      count, electrophoresis, immunoglobulin level, lactate dehydrogenase (LDH), C
      reactive protein, b2 microglobulin concentration, liver and renal function tests
      and there was also a monthly neurological examination. Bone marrow aspiration was
      performed every 3 months during the 12-month treatment. RESULTS: Among 53
      evaluable patients, a clinical response was observed in 27 (51%): there was a
      major response in 7 patients, a partial response in 12 and a minor response in 8.
      INTERPRETATION AND CONCLUSIONS: In responding patients the earliest response was
      observed after 4 weeks of treatment and the latest after 12 weeks of treatment.
      Our results, obtained during a long observation period, show that thalidomide is
      an effective drug, with an acceptable degree of toxicity, in patients with
      refractory multiple myeloma.

PMID- 11325648
TI  - Salvage therapy with thalidomide in multiple myeloma patients relapsing after
      autologous peripheral blood stem cell transplantation.
AB  - BACKGROUND AND OBJECTIVES: The introduction of high-dose therapy with stem cell
      support has significantly improved the outcome of patients with multiple myeloma
      (MM) in terms of increased complete remission (CR) rate and extended survival,
      both disease-free and overall. Few options, however, are presently available for
      patients who relapse after single or double autologous stem cell transplantation
      (SCT). Thalidomide, a glutamic acid derivative with anti-angiogenetic properties,
      has been recently proposed as salvage treatment for such patients. The present
      study was aimed at evaluating thalidomide as single agent therapy for patients
      who had previously received autologous peripheral blood stem cell
      transplantation. DESIGN AND METHODS: From October 1999 to August 2000, 11
      patients (7 males/4 females) who had relapsed after single (n = 4) or double (n =
      7) autologous peripheral blood SCT were enrolled in the trial. Thalidomide,
      always employed as a single agent, was initially administered at a dose of 100
      mg/day; if well tolerated, the dose was increased serially by 200 mg every other
      week to a maximum of 800 mg/day. RESULTS: The median administered dose was 600
      mg/day. WHO grade > II toxic effects were constipation, lethargy, and leukopenia.
      Four patients (36%) showed > 50% reduction in serum M protein concentration and 4
      showed > 25% reduction, for a total response rate averaging 72%. After a median
      follow-up of 5 months, 3 out of 8 responding patients are alive and progression
      free and 5 patients have relapsed. INTERPRETATION AND CONCLUSIONS; These data
      confirm that thalidomide is active in poor-prognosis MM patients such as those
      relapsing after autologous SCT, and could thus deserve further testing in
      combination therapy.

PMID- 11325649
TI  - New mutations in exon 28 of the von Willebrand factor gene detected in patients
      with different types of von Willebrand's disease.
AB  - BACKGROUND AND OBJECTIVES: von Willebrand's disease (vWD), the most common
      hereditary bleeding disorder in humans, is caused by qualitative and/or
      quantitative deficiencies of von Willebrand factor, and can manifest itself under
      several different phenotypes. Most of the molecular defects have been detected in
      qualitative variants involving exon 28 of the vWF gene. Patients from four
      unrelated families with different types of vWD were included in the mutation
      screening of this region. DESIGN AND METHODS: The whole exon 28 was analyzed in
      three gene specific fragments, two of them comprising the region involved in the
      platelet glycoprotein Ib vWF interaction. The search for mutations was carried
      out by single-stranded conformation polymorphism analysis. The mutations were
      then identified by automatic sequencing of the anomalous electrophoretic pattern
      samples. RESULTS: The following candidate mutations were detected. The 3941T-->A
      transversion, which predicts the amino acid change V1314D, was detected in a
      sporadic patient with type 2B vWD and severe thrombocytopenia. The 4309G-->A
      transition, resulting in the amino acid substitution A1437T, was identified in
      four patients classified as having type 2M vWD. Six unclassified patients from
      another family carry the 4135C-->T mutation, which gives rise to a cysteine
      instead of the normal arginine (R1379C) that segregates with the phenotype. The
      amino acid change C1227R, predicted by the mutation 4135C-->T, was identified as
      a compound heterozygote in a patient with moderately severe type 1 vWD. None of
      these mutations had been described previously. INTERPRETATION AND CONCLUSIONS:
      These findings confirm the importance already given to this region for the
      correct function of von Willebrand factor since the mutations detected, which
      affect the D3 and A1 domains, could give rise to different variants of the
      disease.

PMID- 11325650
TI  - Clinical features and laboratory patterns in a cohort of consecutive Argentinian
      patients with von Willebrand's disease.
AB  - BACKGROUND AND OBJECTIVES: von Willebrand's disease (vWD) is a bleeding disorder
      with variable clinical expression. Our aim was to classify patients with vWD and
      to determine the phenotype in their relatives. DESIGN AND METHODS: The types and
      subtypes, blood group frequency and its relevance, bleeding sites, response to
      the desmopressin (DDAVP) test, transfusion requirements and clinical features in
      type 1 and 2A families were determined in 1,885 patients. RESULTS: Our findings
      were: type 1: 91%, type 2A: 3.1%, severe vWD: 1.3%; type 2N: 1.6%; type low
      intraplatelet: 2.7%; combined 1+ 2N: 0.3%. Blood group O prevalence was 70.5%.
      Bleeding and transfusion requirements were not correlated to blood groups. The
      most frequent symptoms were: ecchymoses-hematomas and epistaxis and, in females
      over 13 years, also menorrhagia. Normal levels of factor VIII:C were found in
      38.4% of the patients. DDAVP was infused in 567 patients with a good response in
      80.6%. About 9% of our patients needed transfusion therapy. The diagnosis of von
      Willebrand's disease is more likely in subjects belonging to families with type
      2A disease than in members of families with type 1 vWD in spite of these being
      symptomatic. INTERPRETATION AND CONCLUSIONS: These observations provide a good
      strategy to identify, classify and treat vWD patients without performing
      molecular assays.

PMID- 11325651
TI  - Familial thrombophilia and the occurrence of fetal growth restriction.
AB  - BACKGROUND AND OBJECTIVES: To evaluate the association between unexplained or
      gestational-hypertension-associated fetal growth restriction (FGR) and factor V
      Leiden, prothrombin A20210 mutations, and methylenetetrahydrofolate reductase
      (MTHFR) TT 677 genotype. DESIGN AND METHODS: Sixty-one women with a previous
      history of FGR and 93 parous women with uneventful pregnancies from the same
      ethnic background were investigated for the presence of factor V (FV) Leiden,
      prothrombin A20210 mutations, and MTHFR TT 677 genotype. Moreover,
      antiphospholipid antibodies, antithrombin, protein C, and total and free protein
      S antigen were determined in all patients. RESULTS: Among the controls, 2 (2.2%)
      carried the FV Leiden mutation, 19 (20.4%) were TT MTHFR homozygotes and 1 (1.6%)
      carried the prothrombin A20210 allele. The FV Leiden mutation was present in 8
      women with FGR (13.1%, OR: 6.9, 95%CI 1.4-33.5), the TT MTHFR homozygosity in 17
      (27.8%, OR: 1.5, 95%CI 0.7-3.2) and the A20210 prothrombin allele in 7 (11.5%,
      OR: 5.9, 95%CI 1.2-29.4). In six cases (9.8%) there was coexistence of more than
      one mutation (2 had the FV Leiden and the TT MTHFR genotype and 4 carried the
      A20210 prothrombin allele and TT MTHFR genotype). A logistic regression analysis
      showed that FV Leiden and A20210 prothrombin mutations were independently
      associated with the occurrence of FGR. INTERPRETATION AND CONCLUSIONS: Present
      data indicate an association between prothrombotic genetic factors and FGR.

PMID- 11325652
TI  - Diagnosis of concurrent hemoglobin H disease and heterozygous beta-thalassemia.
AB  - Definitive diagnosis of concurrent hemoglobin (Hb) H disease and heterozygous
      beta-thalassemia cannot be made from Hb analysis alone, but necessitates genotype
      analysis and family study. Interactions between alpha- and beta-thalassemia must
      be considered when investigating moderate to severe hypochromic microcytic anemia
      of uncertain cause in adult patients from areas with a high prevalence of globin
      gene mutations.

PMID- 11325653
TI  - Cyclophosphamide and antithymocyte globulin conditioning may be sufficient for
      Korean patients with early stage severe aplastic anemia transplanted with marrow
      from donors other than HLA-identical siblings.
AB  - We gave a regimen of cyclophosphamide and antithymocyte globulin (CY/ATG) to six
      patients with early stage severe aplastic anemia (SAA) transplanted with marrow
      from alternative donors. All patients engrafted and are alive with durable
      engraftment at a median follow-up of 406 days. The CY/ATG regimen may be
      sufficient in Korean patients with early stage SAA receiving marrow
      transplantation from alternative donors.

PMID- 11325654
TI  - Molecular evaluation of the NUP98/RAP1GDS1 gene frequency in adults with T-acute
      lymphoblastic leukemia.
AB  - The NUP98/RAP1GDS1 (NRG) is a new fusion gene, originating from the
      t(4;11)(q21;p15) translocation, that characterizes a subset of T-cell acute
      lymphoblastic leukemia (T-ALL). In this study we analyzed 43 T-ALL patients for
      the expression of this new molecular marker using a reverse transcription
      polymerase chain reaction (RT-PCR) system, which is more sensitive and specific
      than cytogenetics alone, confirming that NRG-positive ALLs are infrequent,
      accounting for approximately 5% of cases.

PMID- 11325655
TI  - Karyotype and prognosis in adult Spanish acute lymphoblastic leukemia.
AB  - The aim of the study was to define the frequency and prognostic significance of
      acquired chromosomal abnormalities in our adult population and to ascertain
      whether karyotype represents a significant prognostic factor in adult patients
      with acute lymphoblastic leukemia (ALL) independently of the new intensive
      chemotherapy programs and initial clinical characteristics.

PMID- 11325656
TI  - The association of topotecan and cytarabine in the treatment of secondary or
      relapsed acute myeloid leukemia.
AB  - A topotecan/cytarabine combination has been reported to be effective in patients
      with myelodysplastic syndromes. We report our experience with this regimen in 12
      patients with relapsed or secondary acute myeloid leukemia. Extra-hematologic
      toxicity was low, but the response to the treatment was very poor. In our
      opinion, this association is not a treatment option for these patients, but the
      addition of other agents could improve this results.

PMID- 11325657
TI  - Absence of gallium uptake in multicentric Castleman's disease of plasma cell
      type.
AB  - Multicentric Castleman's disease (MCD) of plasma cell type is a reactive
      lymphoproliferative disease. While 67Ga scanning is useful in the detection of
      malignant lymphomas, its role in reactive lymphadenopathy is unknown. We report
      the absence of 67Ga uptake in three patients with MCD of plasma cell type and
      present a review of the English literature on this condition.

PMID- 11325658
TI  - The irreplaceable image: A patient with subacute degeneration of the spinal cord
      secondary to pernicious anemia.

PMID- 11325659
TI  - The irreplaceable image: A giant hepatic mass of myeloid metaplasia in a patient
      without myelofibrosis.

PMID- 11325660
TI  - The irreplacwable image: Acute myeloid leukemia (FAB-M4) with eosinophilia in a
      patient with metastatic breast cancer.

PMID- 11325661
TI  - The irreplaceable image: A case of metastatic malignant melanoma with bone marrow
      involvement.

PMID- 11325662
TI  - The irreplaceable image. Thalidomide in refractory myeloma patients: early
      changes in bone marrow cellularity.

PMID- 11325663
TI  - Aeromonas sobria sepsis in a neutropenic patient.

PMID- 11325664
TI  - Clinical efficacy of recombinant activated factor VII (rFVIIa) during acute
      bleeding episode and surgery in a patient with acquired hemophilia A with high
      inhibitor titer.

PMID- 11325665
TI  - A very rare patient with states for HbH disease and congenital heart disease.

PMID- 11325666
TI  - The use of autologous stem cell transplantation in the treatment of regionally
      advanced nasopharyngeal carcinoma.

PMID- 11325667
TI  - Sodium ferric gluconate complex in the treatment of iron deficiency for patients
      on dialysis.
AB  - Intravenous iron has been found to be an important adjunctive therapy in the
      treatment of anemia for patients on dialysis. In the United States, iron dextran
      had been the only form available for parenteral use until 1999. This agent has
      been associated with a concerning number of severe adverse reactions, in some
      cases resulting in patients' deaths. Recently, a form of iron used for many years
      in Europe, sodium ferric gluconate complex in sucrose, was approved for
      intravenous use in the United STATES: Because this agent does not contain the
      immunogenic dextran component of iron dextran, it is expected that the safety
      profile of this drug should be superior to that of iron dextran. The purpose of
      this review is to critically appraise the relevant literature and to synthesize
      the information into a strategy for clinical use of this drug.

PMID- 11325668
TI  - Cause of residual hypertension after adrenalectomy in patients with primary
      aldosteronism.
AB  - The cause of residual hypertension after adrenalectomy for primary aldosteronism
      (PA) is unknown. The purpose of this study is to investigate the characteristic
      pathological kidney features associated with PA. Between 1977 and 1999 at our
      hospital, 26 patients with PA caused by a unilateral adrenal cortical adenoma
      (Conn's syndrome) underwent unilateral adrenalectomy with concurrent open-wedge
      renal biopsy. Patients were categorized into two groups: (1) those with
      normotension with diastolic blood pressure less than 90 mm Hg who were not
      administered antihypertensive drugs, and (2) those with residual hypertension
      with diastolic blood pressure of 90 mm Hg or greater who were administered
      medication for 6 months after surgery. Thirteen patients were cured of
      hypertension postoperatively, and 12 patients were administered antihypertensive
      medications. Glomerulosclerosis, renal arteriolosclerosis, and preoperative left
      ventricular mass (LVM) index were worse in the group with residual hypertension
      than in that with normotension (17.8% +/- 7.8% versus 9.6% +/- 3.8%; P = 0.01;
      2.5 +/- 0.5 versus 1.6 +/- 0.4, Bader's grade; P = 0.005; and 165 +/- 31 versus
      139 +/- 24 g/m(2); P = 0.02, respectively). Severity of tubulointerstitial
      injury, preoperative duration of hypertension, preoperative severity of
      proteinuria, plasma aldosterone level, and serum potassium concentration were not
      significantly different between the two groups. In conclusion, severity of
      glomerulosclerosis and arteriolosclerosis and LVM are related to blood pressure
      after adrenalectomy in patients with PA.

PMID- 11325669
TI  - Long-term comparison between perindopril and nifedipine in normotensive patients
      with type 1 diabetes and microalbuminuria.
AB  - The aim of this study is to compare the efficacy of an angiotensin-converting
      enzyme inhibitor with a dihydropyridine calcium channel blocker in preventing
      progression to macroalbuminuria and/or a decline in renal function in
      normotensive patients with type 1 diabetes and microalbuminuria. Forty-two
      patients were randomized to treatment with either perindopril, slow-release
      nifedipine, or placebo. In the first 3 months, drug dosage was titrated to
      achieve a decrease in diastolic blood pressure of at least 5 mm HG: Thirty-three
      patients had a minimum of 24 months' data, and 25 patients were followed up
      beyond 36 months (mean, 67 +/- 4 months). Patients were studied every 3 months
      and at the end of the treatment period; those who remained normotensive
      discontinued therapy and were followed up for an additional 3 months. Baseline
      geometric mean albumin excretion rates (AERs) were as follows: perindopril, 66
      microg/min; nifedipine, 59 microg/min; and placebo, 66 microg/min. During the
      first 3 years, 7 of the perindopril-treated but none of the placebo or nifedipine
      treated patients reverted to normoalbuminuria (P < 0.01). Median AERs at 3 years
      of treatment in each group were 23 microg/min for perindopril, 122 microg/min for
      nifedipine, and 112 microg/min for placebo patients (P < 0.01). In patients with
      more than 3 years' follow-up, median AERs decreased by 45% in the first year and
      then stabilized in the perindopril group, but increased by 17.6% in the
      nifedipine group and 27.6% in the placebo group (P < 0.03) in the first year,
      then increased progressively. In these same patients, there was a significant
      decline in glomerular filtration rate in the nifedipine group (-7.8 +/- 1.8
      mL/min/1.73 m(2)/y), but not in the other two groups (perindopril, -1.0 +/- 1.2
      mL/min/1.73 m(2)/y; placebo, -1.3 +/- 1.1 mL/min/1.73 m(2)/y; P = 0.004). At the
      end of the study, cessation of treatment for 3 months was associated with a
      doubling of AERs in the perindopril-treated group, but no change in the other two
      groups (P < 0.001). In conclusion, long-term perindopril therapy is more
      effective than nifedipine or placebo in delaying the progression of diabetic
      nephropathy and reducing AER to the normoalbuminuric range (<20 microg/min) in
      normotensive patients with type 1 diabetes and microalbuminuria.

PMID- 11325670
TI  - Effects of aging and alterations in dietary sodium intake on total nitric oxide
      production.
AB  - Animal studies suggest that nitric oxide (NO) deficiency is linked to salt
      sensitive hypertension and that NO activity decreases during normal aging. This
      study investigates the impact of increasing age and manipulations in dietary salt
      intake on biochemical indices of the NO system in healthy humans. We measured
      NO(2) + NO(3) (NO(X); stable oxidation products of NO) and cyclic guanosine
      monophosphate (cGMP; major second messenger) in plasma and urine of 30 healthy
      subjects aged 22 to 77 years. Subjects were maintained on controlled low NO(X)
      and low-, normal-, or high-salt diets for 3 days. Salt sensitivity of blood
      pressure was seen only in the oldest subjects. Plasma renin activity was
      suppressed by a high salt intake in all age groups, and baseline values declined
      with advancing age. Neither age nor salt intake correlated with indices of NO
      activity over the third 24-hour period of controlled salt intake. In a subgroup
      of subjects aged 33 +/- 4 years challenged with ultrahigh sodium intake (400
      mEq/24 h), again there was no increase in NO(2) + NO(3) or cGMP measures. In
      contrast to animal studies, there is no correlation in humans between either salt
      intake or age and total NO production and activity, indicated by NO(2) + NO(3)
      and cGMP measures. This does not preclude undetected alterations occurring in NO
      production and/or activity in strategic locations in the kidney and
      cardiovascular system. Limitations of blood and urine measurements of NO(2) +
      NO(3) and cGMP as indices of NO activity are discussed.

PMID- 11325671
TI  - Minimal change nephrotic syndrome in children with intrauterine growth
      retardation.
AB  - It has been well established that intrauterine growth retardation (IUGR) is
      associated with greater morbidity and mortality rates during perinatal and adult
      life. The aim of this study is to clarify whether IUGR, defined as a birth weight
      less than the 10th percentile for gestational age, influences the clinical course
      of minimal change nephrotic syndrome (MCNS) in children. The study included 50
      children aged 1 to 13 years at the onset of MCNS. The diagnosis of MCNS was
      confirmed by renal biopsy in 25 children (50%). Eight children (16%) had IUGR at
      birth. Comparisons between children with and without IUGR showed significant
      differences in mean number of relapses (13.0 +/- 3.5 versus 3.4 +/- 3.0 relapses;
      P < 0.0001) and relapse rates (relapses per year, 1.6 +/- 0.3 versus 0.5 +/- 0.4;
      P < 0.0001). We also observed a greater incidence of steroid dependence (100%
      versus 21.4%; P < 0.001) in children with than without IUGR. In addition,
      children with IUGR underwent treatment with cytotoxic agents and cyclosporine
      more frequently than those without IUGR. There was a significantly greater
      incidence of complications and concomitant diseases of nephrotic syndrome in
      children with IUGR; results show that MCNS in children with IUGR had a more
      unfavorable course and outcome. It is important for clinicians to be aware that
      IUGR may help in the early identification of children at greater risk for
      frequent relapses and the development of steroid dependence and/or steroid
      resistance. More aggressive therapy may be indicated for these children.

PMID- 11325672
TI  - Low birth weight and reduced renal volume in Aboriginal children.
AB  - Low birth weight predisposes to renal disease in Aboriginal adults. This could be
      due to reduced nephron numbers, which might be reflected in lower kidney volumes,
      at least early in life. In this study we evaluated the association of birth
      weight with renal volume in 174 children and in adolescents 5 to 18 years old in
      an Aboriginal community with high rates of renal disease. Their mean birth weight
      was 2.9 kg, and 19% had been low birth weight (<2.5 kg). Kidney dimensions were
      measured by ultrasound by a single observer, and kidney volume (KV) was
      calculated from the formula KV (mL) = length x (depth 1 + depth 2)/2 x 0.523.
      Combined kidney volume, corrected for body surface area (corrKV), was independent
      of age and averaged 240 +/- 45 mL/1.73 m(2). The average corrKV was significantly
      lower (by about 20 mL) in low birth weight children than in those with "normal"
      birth weight. There was a difference of 32 mL in combined corrKV between children
      in the lowest versus the highest quintile of birth weight. Disparities in
      calculated kidney volume were driven more by lower kidney depth than length in
      low birth weight children. We conclude that low birth weight children have lower
      renal volumes than children of higher birth weights, after correction for current
      body size. This conclusion is compatible with the theory that intrauterine growth
      retardation is associated with reduced nephron endowment. The susceptibility to
      renal disease associated with low birth weight in this population might be
      mediated in part through this mechanism.

PMID- 11325673
TI  - Reducing racial disparities in transplant activation: whom should we target?
AB  - Several studies have documented that blacks with end-stage renal disease (ESRD)
      are less likely than whites to be placed on the waiting list for a renal
      transplant. We examined trends in access over time to determine whether
      publication of these reports resulted in a reduction in disparity and identified
      those blacks who were most affected to focus future interventions. Three
      nationally representative groups of adult patients with ESRD (first dialysis in
      1986 to 1987, 1990, or 1993) were followed up longitudinally to ascertain the
      date of first placement on the renal transplant waiting list. Cox proportional
      hazards models were used to characterize the magnitude of racial disparities in
      access to the waiting list with adjustment for clinical and sociodemographic
      factors. Lower rates of placement on the waiting list for blacks than whites
      persisted after adjustment for differences in both sociodemographic
      characteristics and health status (relative hazard [RH], 0.68; 95% confidence
      interval [CI], 0.59 to 0.79). The gap between blacks and whites did not narrow
      over time (blacks versus whites: 1986 to 1987 group, RH, 0.71; 95% CI, 0.59 to
      0.86; 1990 group, RH, 0.69; 95% CI, 0.54 to 0.91; 1993 group, RH, 0.57; 0.43 to
      0.77) and was greatest for the youngest and healthiest black patients, who were
      50% and 40% less likely to be listed than corresponding whites, respectively.
      Interventions targeted toward young and healthy blacks, who are most likely to
      benefit from transplantation, are urgently needed to narrow black-white
      differences in transplant activation.

PMID- 11325674
TI  - Quantitative heel ultrasound in assessment of bone structure in renal transplant
      recipients.
AB  - Many patients with advanced renal disease have osteopenia or even osteoporosis by
      the definition of the World Health Organization based on bone mineral density
      (BMD). Dual-energy X-ray absorptiometry (DXA), the standard method to assess BMD,
      is not always available. Quantitative heel ultrasound (QUS) is an inexpensive,
      mobile, and radiation-free diagnostic alternative, yet few data address this
      method's usefulness in patients with renal disease. The present study assessed
      the value of QUS in detecting changes in bone structure in renal transplant
      recipients compared with DXA. In a cross-sectional analysis, 50 patients (29
      women) with a mean age of 50 +/- 13 years, mean time since transplantation of 60
      months (range, 1 to 205 months), and stable renal allograft function were
      studied. BMD was quantified by DXA of the hip and spine. QUS of the left heel
      measured broadband ultrasound attenuation (BUA) and speed of sound (SOS).
      Stiffness index (SI) was calculated as SI = (0.67 * BUA + 0.28 * SOS) - 420. DXA
      measurements established the diagnoses of osteopenia and osteoporosis in 49% and
      22% of the patients, respectively. Femoral neck BMD and QUS parameters showed
      good correlation (r = 0.638; P < 0.001). Sensitivities of BUA, SOS, and SI for
      diagnosing osteoporosis were 100%, and specificities were 73%, 76%, and 78%,
      respectively. Positive predictive values were 50%, 53%, and 56%, and negative
      predictive values were 100%. QUS can be recommended for screening patients who do
      not have osteoporosis. Those suspected of osteopenic bone structure should be
      examined by additional DXA measurement for quantification before initiation of
      therapy.

PMID- 11325675
TI  - Evaluation of disease-state management of dialysis patients.
AB  - Dialysis patients are the only Medicare beneficiaries prohibited from joining
      managed care plans. Concerns have been raised about the ability of such plans to
      provide the comprehensive care required by patients with this complex condition.
      However, more than 20,000 dialysis patients belong to such plans because they
      were enrolled before developing end-stage renal disease (ESRD). Disease-state
      management, successfully applied to patients with diabetes mellitus and
      congestive heart failure, is now being used in patients with ESRD. Standardized
      mortality ratios (SMRs) and standardized hospitalization ratios (SHRs) were
      calculated for 1998 and 1999 in 1,541 patients enrolled in the RMS Disease
      Management program of renal disease-state management using US Renal Data System
      methods. SMRs were 0.643 and 0.806 for 1998 and 1999, respectively, significantly
      different from 1.0 for both years (P < 0.001). SHRs were 0.620 and 0.503 for 1998
      and 1999, respectively, significantly different from 1.0 for both years (P <
      0.001). Although additional studies are needed to define the aspects of care that
      are most important for the outcomes seen, this study shows that favorable
      outcomes are achievable for this vulnerable patient population within a managed
      care setting that applies coordinated approaches to care.

PMID- 11325676
TI  - Predictors of arteriovenous graft patency after radiologic intervention in
      hemodialysis patients.
AB  - Arteriovenous grafts in hemodialysis patients are prone to recurrent stenosis and
      thrombosis, requiring frequent radiologic and surgical interventions to optimize
      their long-term patency. Little is known about the factors that determine graft
      outcome after a radiologic intervention. The present study examined the clinical
      and radiologic predictors of intervention-free graft survival after elective
      angioplasty or thrombectomy. A prospective computerized database was used to
      determine the outcomes subsequent to all graft angioplasties (n = 330) and
      thrombectomies (n = 326) performed at the University of Alabama at Birmingham
      between April 1, 1996, and June 30, 1999. Primary graft survival rates after
      angioplasty and thrombectomy were 86% versus 43% at 1 month, 71% versus 30% at 3
      months, 51% versus 19% at 6 months, and 28% versus 8% at 12 months, respectively.
      The median intervention-free graft survival time was substantially longer after
      angioplasty than thrombectomy (6.7 versus 0.6 months; P < 0.001). The superior
      outcome of angioplasty over thrombectomy was observed even for the subset of
      procedures with no residual stenosis (median survival, 6.9 versus 2.5 months; P <
      0.001). The median graft survival was inversely related to the magnitude of
      residual stenosis for both elective angioplasty and thrombectomy. Median
      intervention-free graft survival after angioplasty was inversely related to the
      postangioplasty intragraft to systemic systolic pressure ratio (7.6, 6.9, and 5.6
      months for ratios <0.4, 0.4 to 0.6, and >0.6, respectively; P < 0.001).
      Intervention-free graft survival after angioplasty or thrombectomy was not
      affected by graft location (forearm versus upper arm), number of stenotic sites,
      or presence of diabetes. In conclusion, graft survival is substantially longer
      after elective angioplasty than thrombectomy, even when the radiologic appearance
      after the procedure suggests complete resolution of the stenotic lesion.
      Moreover, the risk for requiring a subsequent graft intervention can be predicted
      from two simple radiologic measurements: grade of stenosis and intragraft to
      systemic systolic blood pressure ratio. These parameters may help determine the
      frequency of monitoring for recurrent stenosis in a given graft.

PMID- 11325677
TI  - Selective sequestration of cytokine-producing monocytes during hemodialysis
      treatment.
AB  - Hemodialysis treatment leads to leukocyte activation and cytokine production.
      Studying this effect has been complicated because cell activation by blood
      membrane contact also induces adherence factors on leukocytes, leading to
      margination of cells to the endothelium of the lung. Using single-cell cytokine
      determination, we studied the relation between cytokine production and cell
      sequestration during dialysis therapy. Blood was sampled in 11 chronic
      hemodialysis patients using hemophane dialyzers before hemodialysis and at 20 and
      120 minutes of treatment. Lipopolysaccharide (LPS)-induced cytokine production in
      monocytes was studied by intracellular staining for interleukin-6 (IL-6) and IL
      10 and flow cytometry. Results obtained in dialysis patients were compared with
      samples from an ex vivo dialysis system. Monocyte maturation stage was evaluated
      by detection of several surface markers through flow cytometry. Within 20 minutes
      of hemodialysis, the numbers of circulating monocytes decreased to one third of
      initial values. Before dialysis, 56.7% +/- 15.7% of circulating monocytes
      responded to LPS by the production of IL-6. This fraction decreased to 21.1% +/-
      17.3% (P < 0.001 versus before hemodialysis) at 20 minutes and 32.3% +/- 13.8% (P
      < 0.001 versus before hemodialysis) at 120 minutes of treatment. A similar
      decrease occurred for IL-10. Cytokine-positive cells did not decrease during ex
      vivo dialysis. Surface marker studies showed that mature monocytes expressing HLA
      DR or CD86 were predominantly removed. We provide the first evidence for a
      subtype-specific sequestration of monocytes caused by dialysis treatment. Fully
      differentiated cells capable of cytokine production and antigen presentation are
      removed and relatively immature cells remain in circulation.

PMID- 11325678
TI  - Vitamin E suppresses 5-lipoxygenase-mediated oxidative stress in peripheral blood
      mononuclear cells of hemodialysis patients regardless of administration route.
AB  - A number of pathological conditions caused by oxidative stress have been reported
      in uremic patients undergoing maintenance hemodialysis (HD). Enhanced lipid
      peroxidation was previously observed in peripheral blood mononuclear cells
      (PBMCs) of HD patients. Upregulation of 5-lipoxygenase (5-Lox) activity and
      protein content with enhanced production of leukotriene B(4) (LTB(4)) and
      membrane lipoperoxides was also shown in PBMCs of HD patients. Administration of
      free vitamin E specifically inhibited 5-Lox activity without affecting gene
      expression at the protein level. To assess whether oral or intramuscular (IM)
      administration of vitamin E may suppress 5-Lox in HD patients, PBMCs from 16
      subjects on maintenance HD therapy for at least 6 months were investigated before
      and after a short course of IM or oral administration of vitamin E (8 patients
      per group). PBMCs from 13 healthy controls were also evaluated and assumed as the
      reference standard. Vitamin E significantly reduced lipid peroxidation, LTB(4)
      content, and 5-Lox activity in PBMCs, whereas 5-Lox gene expression at the
      protein level was not affected. There were no significant differences in these
      parameters between patients treated with IM or oral vitamin E. PBMCs of HD
      patients showed enhanced membrane lipid peroxidation and release of LTB(4), both
      linked to upregulation of 5-LOX: 5-Lox activity and related oxidative stress were
      significantly (although not completely) suppressed by vitamin E regardless of the
      administration route.

PMID- 11325680
TI  - Predicting a patient's choice of dialysis modality: experience in a United
      Kingdom renal department.
AB  - Education and counseling are important aspects of the management of patients
      starting dialysis. Free choice of modality may enhance patient well-being and, in
      the absence of clear survival benefits for either hemodialysis (HD) or continuous
      ambulatory peritoneal dialysis (CAPD), should have the major role in modality
      selection. This prospective study examines factors influencing this choice. Three
      hundred thirty-three new patients started renal replacement therapy at Birmingham
      Heartlands Hospital (Birmingham, UK) between August 1, 1992, and July 31, 1998.
      Data were incomplete for 14 patients, 11 patients were not counseled, and 54
      patients had contraindications to a particular modality. The remaining 254
      patients were offered a free choice. One hundred thirty-nine patients (55%) chose
      HD and 115 patients (45%) chose CAPD. Independent predictors for choosing CAPD
      rather than HD were being married (P = 0.004), being counseled before the start
      of dialysis (P = 0.019), and increased distance from the base unit (P < 0.001).
      Independent predictors for choosing HD were increasing age (P = 0.030) and male
      sex (P = 0.041). Use of these data should enhance planning of dialysis services
      and bring nearer the goal that all new patients with ESRD are able to have the
      dialysis modality of their choice.

PMID- 11325679
TI  - Oxidative stress and increased expression of growth factors in lesions of failed
      hemodialysis access.
AB  - The pathological role of oxidative stress in patients treated by hemodialysis has
      gained increasing recognition in recent years. Because complications related to
      vascular access are a major source of morbidity, immunohistochemical evidence of
      oxidative stress and activation of growth factors were examined in native
      arteriovenous (AV) fistulae (n = 11) and expanded polytetrafluoroethylene (ePTFE)
      grafts (n = 15) recovered from hemodialysis patients at the time of surgical
      revision or resection. To show the presence of oxidative stress in tissues, three
      markers were chosen: N(epsilon)(carboxymethyl)lysine, a structurally identified
      advanced glycation end product; 4-hydroxy-2,3-nonenol, a lipid peroxidation
      product; and redox-active transition metals bound to proteins, a source of Fenton
      chemistry-generated free radicals. Markers of cell growth and proliferation were
      endothelin-1 (ET-1), a potent mitogenic peptide implicated in the formation of
      intimal hyperplasia; transforming growth factor-beta (TGF-beta), a stimulus to
      vascular cell growth and matrix production; and platelet-derived growth factor
      (PDGF), a mediator of intimal hyperplasia. All specimens studied showed
      significant intimal hyperplasia. In general, the neointima close to the vascular
      lumen of the AV fistula and the pseudointima close to the lumen of the ePTFE
      graft were positive for oxidative stress markers. At sites of injury, especially
      in the presence of histological evidence of inflammation and healing, expression
      of oxidative markers was particularly intense. Prominent staining of PDGF was
      shown at sites of anastomotic hyperplasia and in neovasculature. TGF-beta was
      associated with proliferation or repair in both AV fistulae and ePTFE grafts. ET
      1 staining was most intense in the neointima and pseudointima. This study showed
      histochemical colocalization of markers of oxidative stress with growth factors
      known to contribute to intimal hyperplasia.

PMID- 11325681
TI  - Health-related quality of life among dialysis patients in Seattle and Aichi.
AB  - We used the 36-item Short-Form Health Survey to compare health-related quality of
      life (HRQOL) between 104 dialysis patients in Seattle, WA, and 2,178 patients in
      Aichi, JAPAN: Compared with Aichi patients, Seattle patients had lower scores on
      three scales related to physical HRQOL: Physical Functioning (PF; P = 0.03), Role
      Physical (RP; P = 0.004), and Vitality (VT; P < 0.001). However, scores related
      to mental HRQOL were higher for Seattle patients compared with those of Aichi
      patients, which included scores for Role-Emotional (RE; P = 0.005) and Mental
      Health (MH; P < 0.001). Scores for Bodily Pain, General Health Perception, and
      Social Functioning did not differ significantly between the two groups. These
      differences persisted even after potential confounding factors were controlled
      for. However, after taking into account national norm data for the United States
      and Japan, differences in PF and VT disappeared, whereas differences in RP, RE,
      and MH persisted. These results suggest that the higher scores for PF and VT in
      Aichi patients were partly explained by the higher physical HRQOL of the Japanese
      general population. Although these data may not be representative of the total
      dialysis populations in the United States and Japan, they suggest potential
      differences in HRQOL between patients in the two countries. Additional research
      is needed to confirm these results and understand the factors associated with
      these differences. The findings suggest the need for further attention to the
      physical limitations of US dialysis patients and the mental health of Japanese
      dialysis patients.

PMID- 11325682
TI  - Factors influencing survival in hemodialysis patients aged older than 75 years:
      2.5-year outcome study.
AB  - The incidence of malnutrition is widely held to be greater in the elderly, but
      this specific factor has not been extensively studied in elderly dialysis
      patients. In a 30-month follow-up prospective study, we evaluated the role of
      nutrition on the outcome of 290 stable hemodialysis (HD) outpatients aged older
      than 75 years followed up in 20 French HD centers (167 men, 123 women; age, 79.8
      +/- 4.2 years; previous time on dialysis, 41 +/- 38 months). On the same day in
      January 1996, predialysis and postdialysis blood samples were collected according
      to recommended procedures for dialysis quantification. Normalized protein
      catabolic rate, dialysis adequacy parameters, and estimation of lean body mass
      (LBM; expressed as observed/expected LBM values [obs/exp LBM]) were computed from
      predialysis and postdialysis urea and creatinine levels. Overall survival rates
      were 80% and 65% after 1 and 2 years of follow-up, respectively, and were
      significantly less in patients with the lower quartile of obs/exp LBM. In
      univariate analysis using the Cox proportional hazards model, survival was
      significantly influenced by age, albumin level, prealbumin level, body mass
      index, and diabetes, but not by sex, Kt/V, duration of dialysis, cholesterol
      level, hemoglobin level, or obs/exp LBM. In multivariate analysis, no variable
      remained significant. Cardiovascular mortality accounted for 52.1% of the patient
      deaths. We conclude that in elderly HD patients, malnutrition influences overall
      survival despite adequate dialysis treatment.

PMID- 11325683
TI  - Prevalence of infected patients and understaffing have a role in hepatitis C
      virus transmission in dialysis.
AB  - To assess hepatitis C virus (HCV) incidence rates and identify determinants of
      infection among hemodialysis patients, a multicenter study was conducted in 58
      units in ITALY: An initial seroprevalence survey was conducted among 3,492
      patients already on hemodialysis therapy as of January 1997 and among an
      additional 434 patients who began dialysis up to January 1998. HCV antibodies
      were assessed by third-generation enzyme immunoassays. Patients testing
      seronegative at baseline were enrolled into a 1-year incidence study with
      serological follow-up at 6 and 12 months. For patients who seroconverted, an HCV
      RNA assay was performed on stored baseline samples to confirm new infection. A
      nested case-control study was subsequently performed to investigate potential
      risk factors. For each incident case, three controls negative for both HCV
      antibodies and HCV RNA were randomly selected. At enrollment, HCV seroprevalence
      was 30.0%. During follow-up, 23 new HCV cases were documented, with a cumulative
      incidence of 9.5 cases/1,000 patient-years. By logistic regression analysis, an
      increased risk for HCV infection emerged for patients attending the dialysis
      units with a high prevalence of HCV-infected patients at baseline (odds ratio
      [OR], 4.6) and for those attending units with a low personnel-patient ratio (OR,
      5.4). Among extradialysis factors, a history of surgical intervention in the
      previous 6 months (OR, 16.7) significantly increased HCV risk. These findings
      suggest that the combination of understaffing and a high level of infected
      patients in the dialysis setting increases the risk for HCV nosocomial
      transmission. This is likely related to an increased likelihood for breaks in
      infection control measures.

PMID- 11325684
TI  - Identification and treatment of depression in a cohort of patients maintained on
      chronic peritoneal dialysis.
AB  - Depression is the most commonly encountered psychological problem in patients
      with end-stage renal disease (ESRD). Depression has recently been shown to
      significantly impact on the morbidity and mortality of patients undergoing
      therapy for ESRD. The present study was designed as a pilot study to evaluate the
      feasibility of screening a large cohort of patients maintained on chronic
      peritoneal dialysis (CPD) for depression and then pharmacologically treating
      those patients assessed to have clinical depression. One hundred thirty-six
      patients maintained on CPD in our CPD unit were screened for depression using the
      Beck Depression Inventory (BDI), a self-administered questionnaire. Patients with
      scores of 11 or greater were referred to a trained psychiatric interviewer for
      further evaluation to confirm the diagnosis of clinical depression and determine
      whether the patient was a candidate for antidepressant medication. Sixty-seven
      patients had BDI scores of 11 or greater, and 60 of these patients were asked to
      participate in further evaluation and possible therapy. Only 27 patients agreed
      to further study and were evaluated by a trained psychiatric interviewer for
      clinical depression. Twenty-three of these patients were assessed to have
      clinical depression, and 22 patients were eligible for antidepressant medication
      based on their scores on the Hamilton Depression Scale and psychiatric interview.
      Eleven patients completed a 12-week course of therapy with antidepressant
      medication, and their BDI scores decreased from a mean of 17.1 +/- 6.9 (SD) to a
      mean of 8.6 +/- 3.2. Seven patients were treated with sertraline, 2 patients with
      bupropion, and 2 patients with nefazodone. It is concluded that (1) depression is
      commonly present in patients maintained on CPD, (2) the BDI is a useful tool to
      use to screen for clinical depression, and (3) clinical depression is treatable
      with medication in this patient population.

PMID- 11325685
TI  - Intravenous L-carnitine increases plasma carnitine, reduces fatigue, and may
      preserve exercise capacity in hemodialysis patients.
AB  - Exercise capacity in patients with end-stage renal disease (ESRD) remains
      impaired despite correction of anemia. Carnitine insufficiency may contribute to
      impaired exercise and functional capacities in patients with ESRD. Two randomized
      placebo-controlled trials were conducted to test whether intravenous L-carnitine
      improves exercise capacity (assessed by maximal rate of oxygen consumption
      [VO(2max)]) and quality of life (measured by the Kidney Disease Questionnaire
      [KDQ]) in patients with ESRD. In study A, patients were administered L-carnitine,
      20 mg/kg (n = 28), or placebo (n = 28) intravenously at the conclusion of each
      thrice-weekly dialysis session for 24 weeks. In study B, a dose-ranging study,
      patients were administered intravenous L-carnitine, 10 mg/kg (n = 32), 20 mg/kg
      (n = 30), or 40 mg/kg (n = 32), or placebo (n = 33) as in study A. The
      prospective primary statistical analysis evaluated changes in VO(2max) in each
      study and specified that changes in the KDQ were assessed only in the combined
      populations. L-Carnitine supplementation increased plasma carnitine
      concentrations, but did not affect VO(2max) in either study. Because change in
      VO(2max) showed significant heterogeneity, a secondary analysis using a mixture
      of linear models approach on the combined study populations was performed. L
      Carnitine therapy (combined all doses) was associated with a statistically
      significant smaller deterioration in VO(2max) (-0.88 +/- 0.26 versus -0.05 +/-
      0.19 mL/kg/min, placebo versus L-carnitine, respectively; P = 0.009). L-Carnitine
      significantly improved the fatigue domain of the KDQ after 12 (P = 0.01) and 24
      weeks (P = 0.03) of treatment compared with placebo using the primary analysis
      but did not significantly affect the total score (P = 0.10) or other domains of
      the instrument (P > 0.11). Carnitine was well tolerated, and no drug-related
      adverse effects were identified. Intravenous L-carnitine treatment increased
      plasma carnitine concentrations, improved patient-assessed fatigue, and may
      prevent the decline in peak exercise capacity in hemodialysis patients. VO(2max)
      in the primary analysis and other assessed end points were unaffected by
      carnitine therapy.

PMID- 11325686
TI  - Assessment of access blood flow after preemptive angioplasty.
AB  - In an effort to prolong the life of synthetic grafts used for hemodialysis
      access, current recommendations suggest regular monitoring of vascular access by
      means of measurements of access blood flows (ABFs) and/or pressures and prompt
      referral for prophylactic angiography with angioplasty when appropriate. Previous
      data suggested that angioplasty transiently reduces venous pressure, but repeated
      angioplasty is often required. Few data exist on the effect of angioplasty on
      ABF, especially the durability of the response. In this study, we report our
      experience with 49 consecutive angioplasties of 32 synthetic
      polytetrafluoroethylene grafts in which ABF was measured serially preangiography
      and postangiography using the Transonic hemodialysis monitor (Transonic Inc,
      Ithaca, NY). The primary indication for angiography was a low graft ABF rate
      (<600 mL/min). Although the most common site for stenosis was the venous
      anastomosis, the majority of grafts had multiple lesions requiring angioplasty.
      Mean ABF rate increased from 596 +/- 41 to 922 +/- 48 mL/min postangiography, an
      increase of almost twofold. This level of blood flow was maintained for the first
      month, but thereafter ABF began to decrease, reaching 672 +/- 70 mL/min at 3
      months and 658 +/- 93 mL/min at 6 months. Two patients were lost to follow-up
      (one patient died, one patient received a transplant) and 2 grafts were
      electively ligated. The remaining 28 grafts were followed up for at least 6
      months. Four grafts clotted within 3 months of angioplasty and were lost. Nine
      additional grafts required a second intervention (surgical revision, 2 grafts;
      repeated angioplasty, 7 grafts) within 6 months, either for a poor initial
      response to angioplasty or recurrent stenosis. Two of these 9 grafts subsequently
      clotted and were lost. In all, 22 of the 28 grafts remained patent at 6 months
      postangioplasty, and 15 grafts were maintaining an ABF greater than 600 mL/min
      without reintervention at 6 months. In summary, this study indicates that
      preemptive angioplasty of graft stenoses results in an initial doubling of ABF,
      but the effect is temporary, with the average ABF decreasing to baseline values
      by 3 months. Approximately half the grafts required reintervention for either
      thrombosis or recurrent low flow. However, sustained responses with ABF
      maintained at greater than 600 mL/min were achieved in the other half.

PMID- 11325687
TI  - Identification of a novel form of renal glucosuria with overexcretion of
      arginine, carnosine, and taurine.
AB  - Glucosuria occurs in diabetes mellitus, generalized proximal tubular dysfunction
      of Fanconi's syndrome, glucose-galactose malabsorption syndrome, and primary
      renal glucosuria. Patients with primary renal glucosuria have normal blood
      glucose levels, normal oral glucose tolerance test results, and persistent
      glucosuria that may approach the filtered load of glucose in the most severe
      cases. The primary defect is proposed to be in the sodium-glucose cotransporter
      type-2 (SGLT2) located in the apical membrane of S1 segment proximal renal tubule
      cells. Primary renal glucosuria is classified as types A, B, or O based on the
      characteristics of the transport defect. The magnitude of glucosuria has varied
      from 20 to 150 g of glucose excreted in 24 hours. Described inheritance patterns
      have included both autosomal dominant and autosomal recessive mechanisms. Some
      cases have been associated with selective aminoaciduria, distinctly unlike the
      generalized aminoaciduria seen in Fanconi's syndrome. We report the first case of
      primary renal glucosuria with selective overexcretion of arginine, carnosine, and
      taurine. This case may represent a genetic defect unique from the abnormalities
      in previously described cases of primary renal glucosuria with different amino
      acid excretion patterns. Future investigations could determine whether the
      syndrome involves a defect in the SGLT2 gene.

PMID- 11325688
TI  - Hemodialysis followed by continuous hemofiltration for treatment of lithium
      intoxication in children.
AB  - Hemodialysis is the usual recommended treatment for severe lithium intoxication;
      however, rebound of lithium levels may require repeated hemodialysis treatments.
      We proposed that the addition of continuous hemofiltration after hemodialysis
      would prevent rebound by providing ongoing clearance of lithium. We report two
      pediatric patients with lithium intoxication treated by hemodialysis followed by
      continuous venovenous hemofiltration with dialysis (CVVHD). Both patients were
      symptomatic at presentation and had initial lithium levels more than three times
      the usual therapeutic range. Hemodialysis followed by CVVHD resulted in rapid
      resolution of symptoms, followed by continuous clearance of lithium without
      requiring repeated hemodialysis sessions. Both patients had return of normal
      mental status during CVVHD treatment, and neither patient experienced
      complications of hemodialysis or CVVHD. Total duration of treatment with
      hemodialysis followed by CVVHD was 34.5 hours for the first patient and 26 hours
      for the second patient. We conclude that hemodialysis followed by CVVHD is a safe
      and effective approach to the management of lithium intoxication in children.

PMID- 11325689
TI  - Generalized argyria in two chronic hemodialysis patients.
AB  - Silver can be absorbed through ingestion, topical administration, or inhalation.
      Generalized argyria results from deposition of silver in the skin, nails, mucous
      membranes, and internal organs and is characterized by a diffuse bluish-gray
      discoloration in sun-exposed areas. We report two cases of generalized argyria in
      patients on maintenance hemodialysis (HD) therapy for more than 15 years. They
      presented with diffuse hyperpigmentation of the face that was mistaken to be
      related to uremia and bluish-gray discoloration of all nails believed to be
      cyanosis. Histopathologic examination of skin biopsy specimens showed
      characteristic findings of argyria, which was further confirmed by radiograph
      microanalysis. Their serum silver levels were also elevated. No definite silver
      source could be determined. However, their argyria might be related to their long
      term HD therapy because (1) they had been on HD therapy for more than 15 years
      and the discoloration appeared several years afterward, and (2) the water used
      for HD was not well processed in the early 1980s in TAIWAN: Argyria should be
      suspected in chronic HD patients presenting with a diffuse bluish-gray
      discoloration of the skin and nails and evaluated carefully by skin biopsy.

PMID- 11325690
TI  - Hepatitis C virus transmission in the hemodialysis community.

PMID- 11325691
TI  - Dietary phytoestrogens: a possible role in renal disease protection.
AB  - There is growing evidence that dietary phytoestrogens have a beneficial role in
      chronic renal disease. This review summarizes the recent findings from dietary
      intervention studies performed in animals and humans suggesting that consumption
      of soy-based protein rich in isoflavones and flaxseed rich in lignans retards the
      development and progression of chronic renal disease. In several animal models of
      renal disease, both soy protein and flaxseed have been shown to limit or reduce
      proteinuria and renal pathological lesions associated with progressive renal
      failure. In studies of human subjects with different types of chronic renal
      disease, soy protein and flaxseed also appear to moderate proteinuria and
      preserve renal function. However, most of these clinical trials were of
      relatively short duration and involved a small number of patients. Furthermore,
      it is not clear whether the renal protective effects of soy protein and flaxseed
      are caused by the isoflavones (daidzein and genistein) and lignans (matairesinol
      and secoisolariciresinol) or some other component. The biochemistry, metabolism,
      and mechanisms of actions of isoflavones and lignans are discussed. Isoflavones
      and lignans appear to act through various mechanisms that modulate cell growth
      and proliferation, extracellular matrix synthesis, inflammation, and oxidative
      stress. Some of these actions have been shown in vitro, but studies of the
      mechanisms operative in vivo are lacking. The diversity of cellular actions of
      isoflavones and lignans supports their protective effects in a variety of
      experimental and human types of chronic renal disease. Further investigations are
      needed to evaluate their long-term effects on renal disease progression in
      patients with chronic renal failure.

PMID- 11325692
TI  - Hyperammonemia in urea cycle disorders: role of the nephrologist.
AB  - Hyperammonemia associated with inherited disorders of amino acid and organic acid
      metabolism is usually manifested by irritability, somnolence, vomiting, seizures,
      and coma. Although the majority of these patients present in the newborn period,
      they may also present in childhood, adolescence, and adulthood with failure to
      thrive, persistent vomiting, developmental delay, or behavioral changes.
      Persistent hyperammonemia, if not treated rapidly, may cause irreversible
      neuronal damage. After the diagnosis of hyperammonemia is established in an
      acutely ill patient, certain diagnostic tests should be performed to
      differentiate between urea cycle defects and other causes of hyperammonemic
      encephalopathy. In a patient with a presumed inherited metabolic disorder, the
      aim of therapy should be to normalize blood ammonia levels. Recent experience has
      provided treatment guidelines that include minimizing endogenous ammonia
      production and protein catabolism, restricting nitrogen intake, administering
      substrates of the urea cycle, administering compounds that facilitate the removal
      of ammonia through alternative pathways, and, in severe cases, dialysis therapy.
      Initiation of dialysis in the encephalopathic patient with hyperammonemia is
      indicated if the ammonia blood level is greater than three to four times the
      upper limit of normal. Hemodialysis is the most effective treatment for rapidly
      reducing blood ammonia levels. Continuous hemofiltration and peritoneal dialysis
      are also effective modalities for reducing blood ammonia levels. An improved
      understanding of the metabolism of ammonia and neurological consequences of
      hyperammonemia will assist the nephrologist in providing optimal care for this
      high-risk patient population.

PMID- 11325693
TI  - Shared decision-making in dialysis: the new RPA/ASN guideline on appropriate
      initiation and withdrawal of treatment.

PMID- 11325694
TI  - Functional and structural involvement of afferent and efferent glomerular
      arterioles in hypertension.

PMID- 11325695
TI  - Painful myopathy and end-stage renal disease.

PMID- 11325696
TI  - Are the results of carbon dioxide analysis affected by shipping blood samples?

PMID- 11325697
TI  - The measurement of total carbon dioxide (tCO2) in blood specimens.

PMID- 11325698
TI  - Do dialysis patients need a "new nephrologist"?

PMID- 11325701
TI  - Subcutaneous erythropoietin results in lower dose and equivalent hematocrit
      levels among adult hemodialysis patients: Results from the 1998 End-Stage Renal
      Disease Core Indicators Project.
AB  - The National Kidney Foundation's Dialysis Outcome Quality Initiative (NKF-DOQI)
      guidelines recommend that epoetin alfa should be administered by the subcutaneous
      route in hemodialysis patients. We determined whether hematocrit levels in
      hemodialysis patients differed by route of epoetin alfa administration after
      controlling for demographic factors and iron status. Data were available for
      7,092 of the 7,658 patients randomly chosen for inclusion in the 1997 Health Care
      Financing Administration Core Indicators sample. Epoetin alfa was administered to
      96% of the study cohort and was administered subcutaneously in 10% of patients.
      After controlling for hematocrit, patient characteristics, adequacy of dialysis,
      iron status, serum albumin, postdialysis weight, and duration of dialysis, the
      epoetin alfa dose by the intravenous route was 193.6 units/kg/wk (95% confidence
      interval, 189.5 to 197.8 units/kg/wk) compared with 167.4 units/kg/wk (95%
      confidence interval, 153.9 to 180.8 units/kg/wk) for the subcutaneous route (P <
      0.001). The mean hematocrit for the subcutaneous route was 32.7% +/- 3.4% and for
      the intravenous route was 33.0% +/- 3.2% (P < 0.05). Factors independently
      associated with increased hematocrit included male gender, white race, older
      patient age, greater number of years on dialysis, higher serum albumin
      concentration, higher urea reduction ratio, and percent transferrin saturation
      (all P < 0.001). After controlling for patient factors and weekly epoetin alfa
      dose, there was no association between route of epoetin alfa administration and
      hematocrit level (P = 0.144). Patients receiving epoetin alfa by the subcutaneous
      route had comparable hematocrit values using a lower epoetin alfa dose than
      patients receiving epoetin alfa intravenously. These data support the NKF-DOQI
      recommendation that epoetin alfa be administered subcutaneously in long-term
      hemodialysis patients.

PMID- 11325702
TI  - Adenine phosphoribosyltransferase deficiency and renal allograft dysfunction.
AB  - Adenine phosphoribosyltransferase (APRT) deficiency is a rarely diagnosed cause
      of renal allograft dysfunction. We report the case of a 42-year-old man who
      presented in 1996 with idiopathic renal failure. Native kidney biopsy showed
      extensive microcrystalline interstitial nephritis. The patient subsequently
      underwent a living-related kidney transplant with excellent early graft function.
      During the next year, however, he had worsening allograft function, and allograft
      biopsy showed recurrent interstitial nephritis. Further chemical and
      spectroscopic analysis showed this lesion to be an annular microcrystalline
      nephritis consistent with APRT deficiency. This diagnosis was confirmed on
      erythrocyte assay. Treatment with allopurinol and a low-purine diet led to
      improvement and stabilization of renal function. APRT is a rare cause of renal
      allograft dysfunction requiring a high index of suspicion for early diagnosis and
      treatment. Increased physician awareness in the United States may hasten
      diagnosis and limit the morbidity associated with this disease.

PMID- 11325703
TI  - Antineutrophil cytoplasmic autoantibody specific for proteinase 3 in a patient
      with shunt nephritis induced by Gemella morbillorum.
AB  - A 17-year-old girl had been placed with ventriculoperitoneal, then
      ventriculoatrial shunts for congenital hydrocephalus since birth. The patient
      originally was diagnosed as having a lupus-like disease, but later turned out to
      have shunt nephritis, presenting with fever, proteinuria, pancytopenia, and
      hypocomplementemia. Antineutrophil cytoplasmic autoantibody specific for
      proteinase 3 (PR3-ANCA) was detected in her serum. The patient received oral
      prednisolone and repeated methylprednisolone pulses, with essentially no
      beneficial effects. A gram-positive coccus, Gemella morbillorum, was recovered
      from her blood as well as cerebrospinal fluid, and the culture of the shunt
      catheter established the diagnosis of shunt nephritis. Removal of the shunt
      catheter improved symptoms dramatically and decreased PR3-ANCA in serum to an
      undetectable level. Because steroids had no effects and the control of bacterial
      infection lowered PR3-ANCA levels, the antibody would have been induced by
      continuous infection with G morbillorum.

PMID- 11325704
TI  - Hiv-associated nephropathy occurring before HIV antibody seroconversion.
AB  - It currently is thought that human immunodeficiency virus-associated nephropathy
      (HIVAN) occurs late in the course of HIV infection. Although HIVAN may be the
      presenting manifestation of acquired immunodeficiency syndrome (AIDS), it usually
      occurs after a prolonged period of viral infection often associated with high
      levels of HIV viremia. The patient described here developed HIVAN as a
      manifestation of acute retroviral syndrome. A 41-year-old black man presented
      with nephrotic range proteinuria, renal insufficiency, and acute gastrointestinal
      and pulmonary symptoms. He recently had been treated for primary syphilis. Two
      HIV serologic tests, performed 3 months apart, were negative. Renal biopsy was
      consistent with HIVAN. After the biopsy, the patient was discovered to have more
      than 700,000 viral copies per mL in his blood. CD4(+) count was greater than
      500/mm(3). Six weeks later, enzyme-linked immunosorbent assay and Western blot
      analyses for HIV antibody became positive. HIVAN can occur early in the course of
      HIV infection, even during acute infection before seroconversion, and prolonged
      exposure to virus is not necessary for this renal involvement to occur in the
      susceptible host.

PMID- 11325705
TI  - Membranous nephropathy associated with chronic immune thrombocytopenic purpura in
      childhood.
AB  - Membranous nephropathy has been associated with many autoimmune diseases. We
      describe a child with membranous nephropathy associated with chronic immune
      thrombocytopenic purpura (ITP) and Coombs'-positive hemolytic anemia. After 3
      years of ITP, the patient developed nephrotic syndrome during a flare of ITP. A
      biopsy specimen showed membranous nephropathy. Treatment with corticosteroids led
      to improvement of the thrombocytopenia and resolution of the proteinuria. Two
      years later, the patient again developed thrombocytopenia and proteinuria. Both
      conditions resolved after treatment with corticosteroids. This case suggests that
      ITP can cause membranous nephropathy.

PMID- 11325706
TI  - Hyperosmolar syndrome in a patient with uncontrolled diabetes mellitus.
AB  - Nonketotic hyperglycemic hyperosmolar syndrome (HHS) is found mostly in type 2
      diabetic patients with marked hyperglycemia. HHS is a metabolic emergency and is
      associated with a high mortality rate. It is characterized by extreme dehydration
      and neurologic symptoms, which are related directly to the degree of
      hyperosmolality. We describe a 65-year-old patient who was admitted because of
      impaired consciousness caused by HHS. The relevant clinical and laboratory
      findings are discussed, and a brief overview of the pathophysiology and
      therapeutic management is provided.

PMID- 11325707
TI  - pH-dependent structural changes at the Heme-Copper binuclear center of cytochrome
      c oxidase.
AB  - The resonance Raman spectra of the aa3 cytochrome c oxidase from Rhodobacter
      sphaeroides reveal pH-dependent structural changes in the binuclear site at room
      temperature. The binuclear site, which is the catalytic center of the enzyme,
      possesses two conformations at neutral pH, assessed from their distinctly
      different Fe-CO stretching modes in the resonance Raman spectra of the CO complex
      of the fully reduced enzyme. The two conformations (alpha and beta) interconvert
      reversibly in the pH 6-9 range with a pKa of 7.4, consistent with Fourier
      transform infrared spectroscopy measurements done at cryogenic temperatures (D.M.
      Mitchell, J.P. Sapleigh, A.M.Archer, J.O. Alben, and R.B.Gennis, 1996,
      Biochemistry 35:9446-9450). It is postulated that the different structures result
      from a change in the position of the Cu(B) atom with respect to the CO due to the
      presence of one or more ionizable groups in the vicinity of the binuclear center.
      The conserved tyrosine residue (Tyr-288 in R. sphaeroides, Tyr-244 in the bovine
      enzyme) that is adjacent to the oxygen-binding pocket or one of the histidines
      that coordinate Cu(B) are possible candidates. The existence of an equilibrium
      between the two conformers at physiological pH and room temperature suggests that
      the conformers may be functionally involved in enzymatic activity.

PMID- 11325708
TI  - Numerical analysis of Ca2+ depletion in the transverse tubular system of
      mammalian muscle.
AB  - Calcium currents were recorded in contracting and actively shortening mammalian
      muscle fibers. In order to characterize the influence of extracellular calcium
      concentration changes in the small unstirred lumina of the transverse tubular
      system (TTS) on the time course of the slow L-type calcium current (I(Ca)), we
      have combined experimental measurements of I(Ca) with quantitative numerical
      simulations of Ca2+ depletion. I(Ca) was recorded both in calcium-buffered and
      unbuffered external solutions using the two-microelectrode voltage clamp
      technique (2-MVC) on short murine toe muscle fibers. A simulation program based
      on a distributed TTS model was used to calculate the effect of ion depletion in
      the TTS. The experimental data obtained in a solution where ion depletion is
      suppressed by a high amount of a calcium buffering agent were used as input data
      for the simulation. The simulation output was then compared with experimental
      data from the same fiber obtained in unbuffered solution. Taking this approach,
      we could quantitatively show that the calculated Ca2+ depletion in the transverse
      tubular system of contracting mammalian muscle fibers significantly affects the
      time-dependent decline of Ca2+ currents. From our findings, we conclude that ion
      depletion in the tubular system may be one of the major effects for the I(Ca)
      decline measured in isotonic physiological solution under voltage clamp
      conditions.

PMID- 11325709
TI  - "Either-or" two-slit interference: stable coherent propagation of individual
      photons through separate slits.
AB  - In quantum theory, nothing that is observable, be it physical, chemical, or
      biological, is separable from the observer. Furthermore, ". all possible
      knowledge concerning that object is given by its wave function" (Wigner, E. 1967.
      Symmetries and Reflections. Indiana University Press, Bloomington, IN), which can
      only describe probabilities of future events. In physical systems, quantum
      mechanical probabilistic events that are microscopic must, in turn, account for
      macroscopic events that are associated with a greater degree of certainty. In
      biological systems, probabilistic statistical mechanical events, such as
      secretion of microscopic synaptic vesicles, must account for macroscopic
      postsynaptic potentials; probabilistic single-channel events sum to produce a
      macroscopic ionic current across a cell membrane; and bleaching of rhodopsin
      molecules (responsible for quantal potential "bumps") produces a photoreceptor
      generator potential. Among physical systems, a paradigmatic example of how
      quantum theory applies to the observation of events concerns the interactions of
      particles (e.g., photons, electrons) with the two-slit apparatus to generate an
      interference pattern from a single common light source. For two-slit systems that
      use two independent laser sources with brief (<1 ms) intervals of mutual
      coherence (Paul, H. 1986. Rev. Modern Phys. 58:209-231), each photon has been
      considered to arise from both beams and has a probability amplitude to pass
      through each of the two slits. Here, a single laser source two-slit interference
      system was constructed so that each photon has a probability amplitude to pass
      through only one or the other, but not both slits. Furthermore, all photons
      passing through one slit could be distinguished from all photons passing through
      the other slit before their passage. This "either-or" system produced a stable
      interference pattern indistinguishable from the interference produced when both
      slits were accessible to each photon. Because this system excludes the
      interaction of one photon with both slits, phase correlation of photon movements
      derives from the "entanglement" of all photon wave functions due to their
      dependence on a common laser source. Because a laser source (as well as Young's
      original point source) will have stable time-averaged spatial coherence even at
      low intensities, the "either-or" two-slit interference can result from distinct
      individual photons passing one at a time through one or the other slit-rather
      than wave-like behavior of individual photons. In this manner, single, successive
      photons passing through separate slits will assemble over time in phase
      correlated wave distributions that converge in regions of low and high
      probability.

PMID- 11325710
TI  - Effect of anisotropic reactivity on the rate of diffusion-controlled reactions:
      comparative analysis of the models of patches and hemispheres.
AB  - A comparative analysis of two models of anisotropic reactivity in bimolecular
      diffusion-controlled reaction kinetics is presented. One is the conventional
      model of reactive patches (MRP), where the surface of a molecule is assumed to be
      reactive over a certain region (circular patch) with the rest of the surface
      being inert. Another one is the model of reactive hemispheres (MRH), assuming
      that a molecule is reactive within a certain distance from a point on its
      surface. The accuracy of the known and newly derived simple analytical
      expressions for the reaction rate is tested by comparison with the simulation
      results obtained by the original Brownian dynamics method. These formulas prove
      to be quite accurate in the practically important limit of strong anisotropy
      corresponding to small size of the reactive patches or hemispheres. Numerical
      calculations confirm earlier predictions that the MRP rates are much smaller than
      the MRH rates for the same radii of the reactive regions, especially in the case
      where both reacting molecules are anisotropic.

PMID- 11325711
TI  - Structural determinants of MscL gating studied by molecular dynamics simulations.
AB  - The mechanosensitive channel of large conductance (MscL) in prokaryotes plays a
      crucial role in exocytosis as well as in the response to osmotic downshock. The
      channel can be gated by tension in the membrane bilayer. The determination of
      functionally important residues in MscL, patch-clamp studies of pressure
      conductance relationships, and the recently elucidated crystal structure of MscL
      from Mycobacterium tuberculosis have guided the search for the mechanism of MscL
      gating. Here, we present a molecular dynamics study of the MscL protein embedded
      in a fully hydrated POPC bilayer. Simulations totaling 3 ns in length were
      carried out under conditions of constant temperature and pressure using periodic
      boundary conditions and full electrostatics. The protein remained in the closed
      state corresponding to the crystal structure, as evidenced by its impermeability
      to water. Analysis of equilibrium fluctuations showed that the protein was least
      mobile in the narrowest part of the channel. The gating process was investigated
      through simulations of the bare protein under conditions of constant surface
      tension. Under a range of conditions, the transmembrane helices flattened as the
      pore widened. Implications for the gating mechanism in light of these and
      experimental results are discussed.

PMID- 11325712
TI  - Functional dynamics of the hydrophobic cleft in the N-domain of calmodulin.
AB  - Molecular dynamics studies of the N-domain (amino acids 1-77; CaM(1-77)) of Ca2+
      loaded calmodulin (CaM) show that a solvent exposed hydrophobic cleft in the
      crystal structure of CaM exhibits transitions from an exposed (open) to a buried
      (closed) state over a time scale of nanoseconds. As a consequence of burying the
      hydrophobic cleft, the R(g) of the protein is reduced by 1.5 A. Based on this
      prediction, x-ray scattering experiments were conducted on this domain over a
      range of concentrations. Models built from the scattering data show that the R(g)
      and general shape is consistent with the simulation studies of CaM(1-77). Based
      on these observations we postulate a model in which the conformation of CaM
      fluctuates between two different states that expose and bury this hydrophobic
      cleft. In aqueous solution the closed state dominates the population, while in
      the presence of peptides, the open state dominates. This inherent flexibility of
      CaM may be the key to its versatility in recognizing structurally distinct
      peptide sequences. This model conflicts with the currently accepted hypothesis
      based on observations in the crystal structure, where upon Ca2+ binding the
      hydrophobic cleft is exposed to solvent. We postulate that crystal packing forces
      stabilize the protein conformation toward the open configuration.

PMID- 11325713
TI  - Mechanisms of tryptophan fluorescence shifts in proteins.
AB  - Tryptophan fluorescence wavelength is widely used as a tool to monitor changes in
      proteins and to make inferences regarding local structure and dynamics. We have
      predicted the fluorescence wavelengths of 19 tryptophans in 16 proteins, starting
      with crystal structures and using a hybrid quantum mechanical-classical molecular
      dynamics method with the assumption that only electrostatic interactions of the
      tryptophan ring electron density with the surrounding protein and solvent affect
      the transition energy. With only one adjustable parameter, the scaling of the
      quantum mechanical atomic charges as seen by the protein/solvent environment, the
      mean absolute deviation between predicted and observed fluorescence maximum
      wavelength is 6 nm. The modeling of electrostatic interactions, including
      hydration, in proteins is vital to understanding function and structure, and this
      study helps to assess the effectiveness of current electrostatic models.

PMID- 11325714
TI  - In vivo control of soluble guanylate cyclase activation by nitric oxide: a
      kinetic analysis.
AB  - Free nitric oxide (NO) activates soluble guanylate cyclase (sGC), an enzyme,
      within both pulmonary and vascular smooth muscle. sGC catalyzes the cyclization
      of guanosine 5'-triphosphate to guanosine 3',5'-cyclic monophosphate (cGMP).
      Binding rates of NO to the ferrous heme(s) of sGC have been measured in vitro.
      However, a missing link in our understanding of the control mechanism of sGC by
      NO is a comprehensive in vivo kinetic analysis. Available literature data
      suggests that NO dissociation from the heme center of sGC is accelerated by its
      interaction with one or more cofactors in vivo. We present a working model for
      sGC activation and NO consumption in vivo. Our model predicts that NO influences
      the cGMP formation rate over a concentration range of approximately 5-100 nM
      (apparent Michaelis constant approximately 23 nM), with Hill coefficients between
      1.1 and 1.5. The apparent reaction order for NO consumption by sGC is dependent
      on NO concentration, and varies between 0 and 1.5. Finally, the activation of sGC
      (half-life approximately 1-2 s) is much more rapid than deactivation
      (approximately 50 s). We conclude that control of sGC in vivo is most likely
      ultra-sensitive, and that activation in vivo occurs at lower NO concentrations
      than previously reported.

PMID- 11325715
TI  - Cross-correlation analysis of inner-leaflet-anchored green fluorescent protein co
      redistributed with IgE receptors and outer leaflet lipid raft components.
AB  - To investigate the structural basis for membrane interactions that occur between
      Lyn tyrosine kinase and IgE-Fc(epsilon)RI or other components of lipid rafts, we
      prepared a green fluorescent protein analog of Lyn (PM-EGFP) and used cross
      correlation analysis to quantify co-redistributions of aggregates that occur
      after IgE-Fc(epsilon)RI is cross-linked on the cell surface. PM-EGFP, which
      contains minimally the palmitoylation and myristoylation sites on Lyn, was
      compared with another inner leaflet probe, EGFP-GG, which contains a prenylation
      site and a polybasic sequence similar to K-ras. Confocal fluorescence microscopy
      was used to examine co-redistributions of these inner leaflet components with IgE
      Fc(epsilon)RI and outer leaflet raft components, ganglioside GD1b and
      glycosylphosphotidylinositol-linked Thy-1, under conditions where the latter were
      cross-linked externally to form large patches at the cell surface. The cross
      correlation analysis was developed and characterized with simulations
      representing cell surface distributions, and parameters from the cross
      correlation curves, rho(o) (peak height) and A (peak area), were shown to be
      reliable measures of the extent of co-redistributed aggregates and their size.
      Cross-correlation analysis was then applied to quantify co-redistributions of the
      fluorescently labeled inner and outer leaflet components on RBL-2H3 cells. As
      visually observed and parameterized in this manner, PM-EGFP was found to co
      redistribute with lipid rafts significantly more than EGFP-GG or an endogenous
      prenylated protein, Cdc42. These quantitative results are consistent with
      previous analyses of Lyn co-redistributions and support the hypothesis that the
      functionally important interaction of Lyn with cross-linked IgE- Fc(epsilon)RI is
      due to their mutual co-association with lipid rafts.

PMID- 11325716
TI  - Mouse mast cell secretory granules can function as intracellular ionic
      oscillators.
AB  - Fluorescent Ca2+ probes and digital photo-sectioning techniques were used to
      directly study the dynamics of Ca2+ in isolated mast cell granules of normal
      (CB/J) and beige (Bg(j)/Bg(j)) mice. The resting intraluminal free Ca2+
      concentration ([Ca2+]L) is 25 +/- 4.2 microM (mean +/- SD, n = 68). Exposure to 3
      microM inositol 1,4,5-trisphosphate (InsP3) induced periodic oscillations of
      luminal Ca2+ ([Ca2+]L) of approximately 10 microM amplitude and a period around 8
      10 s. The [Ca2+]L oscillations were accompanied by a corresponding oscillatory
      release of [Ca2+]L to the extraluminal space. Control experiments using ruthenium
      red (2 microM) and thapsigargin (100 nM) ruled out artifacts derived from the
      eventual presence of mitochondria or endoplasmic reticulum in the isolated
      granule preparation. Oscillations of [Ca2+]L and Ca2+ release result from a
      Ca2+/K+ exchange process whereby bound Ca is displaced from the heparin
      polyanionic matrix by inflow of K+ into the granular lumen via an apamin
      sensitive Ca2+-sensitive K+ channel (ASK(Ca)), whereas Ca2+ release takes place
      via an InsP3-receptor-Ca2+ (InsP3-R) channel. These results are consistent with
      previous observations of [Ca2+]L oscillations and release in/from the endoplasmic
      reticulum and mucin granules, and suggest that a highly conserved common
      mechanism might be responsible for [Ca2+]L oscillations and quantal periodic Ca2+
      release in/from intracellular Ca2+ storage compartments.

PMID- 11325717
TI  - Localization and kinetics of protein kinase C-epsilon anchoring in cardiac
      myocytes.
AB  - Protein kinase C-epsilon (PKC-epsilon) plays a central role in cardiac cell
      signaling, but mechanisms of translocation and anchoring upon activation are
      poorly understood. Conventional PKC isoforms rely on a rapid Ca2+-mediated
      recruitment to cell membranes, but this mechanism cannot be employed by PKC
      epsilon or other PKC isoforms lacking a Ca2+-binding domain. In this study, we
      used recombinant green fluorescent protein (GFP) fusion constructs and confocal
      microscopy to examine the localization, kinetics, and reversibility of PKC
      epsilon anchoring in permeabilized rat cardiac myocytes. PKC-epsilon-GFP bound
      with a striated pattern that co-localized with alpha-actinin, a marker of the Z
      line of the sarcomere. Binding required activation of PKC and occurred slowly but
      reversibly with apparent rate constants of k(on) = 4.6 +/- 1.2 x 10(3) M(-1) x s(
      1) and k(off) = 1.4 +/- 0.5 x 10(-3) s(-1) (t1/2 = 8 min) as determined by
      fluorescence recovery after photobleaching and by perfusion experiments. A
      truncated construct composed of the N-terminal 144-amino-acid variable region of
      PKC-epsilon (epsilonV1-GFP), but not an analogous N-terminal domain of PKC-delta,
      mimicked the Z-line decoration and slow binding rate of the full-length enzyme.
      These findings suggest that the epsilonV1 domain is important in determining PKC
      epsilon localization and translocation kinetics in cardiac muscle. Moreover, PKC
      epsilon translocation is not a diffusion-controlled binding process but instead
      may be limited by intramolecular conformational changes within the V1 domain. The
      k(off) for epsilonV1-GFP was two- to threefold faster than for full-length
      enzyme, indicating that other domains in PKC-epsilon contribute to anchoring by
      prolonging the bound state.

PMID- 11325718
TI  - Desensitization of NMDA receptor channels is modulated by glutamate agonists.
AB  - Two distinct forms of desensitization have been characterized for N-methyl-D
      aspartate (NMDA) receptors. One form results from a weakening of agonist affinity
      when channels are activated whereas the other form of desensitization results
      when channels enter a long-lived nonconducting state. A weakening of glycine
      affinity upon NMDA receptor activation has been reported. Cyclic reaction schemes
      for NMDA receptor activation require that a concomitant affinity shift should be
      observed for glutamate agonists. In this study, measurements of peak and steady
      state NMDA receptor currents yielded EC50 values for glutamate that differed by
      1.9-fold, but no differences were found for another agonist, L-cysteine-S-sulfate
      (LCSS). Simulations show that shifts in EC50 values may be masked by significant
      degrees of desensitization resulting from channels entering a long-lived
      nonconducting state. Simulations also show that a decrease in the degree of
      desensitization with increasing agonist concentration is a good indicator for the
      existence of desensitization resulting from a weakening of agonist affinity. Both
      glutamate and LCSS exhibited this trend. An affinity difference of three- to
      eightfold between high-and low-affinity agonist-binding states was estimated from
      fitting of dose-response data with models containing both types of
      desensitization. This indicates that activation of NMDA receptors causes a
      reduction in both glutamate and glycine affinities.

PMID- 11325719
TI  - Mechanism underlying slow kinetics of the OFF gating current in Shaker potassium
      channel.
AB  - Based on the structure of the KcsA potassium channel, the Shaker K+ channel is
      thought to have, near the middle of the membrane, a cavity that can be occupied
      by a permeant or a blocking cation. We have studied the interaction between
      cations in the cavity and the activation gate of the channel, using a set of
      monovalent cations together with Shaker mutants that modify the structure of the
      cavity. Our results show that reducing the size of the side chain at position 470
      makes it possible for the mutant channel, unlike native Shaker, to close with
      tetraethylammonium (TEA+) or the long-chain TEA-derivative C10+ trapped inside
      the channel. Neither I470 mutants nor Shaker can close when N-methyl-glucamine
      (NMG+) is in the channel, even though this ion is smaller than C10+. Apparently,
      the carbohydrate side chain of NMG+ prevents gate closing. Gating currents
      recorded from Shaker and I470C were measured in the presence of different
      intracellular cations to further analyze the interaction of cations with the
      gate. Our results suggest that the cavity in Shaker is so small that even
      permeant cations like Rb+ or Cs+ must leave the cavity before the channel gate
      can close.

PMID- 11325720
TI  - Actin modifies Ca2+ block of epithelial Na+ channels in planar lipid bilayers.
AB  - The mechanism by which the cytoskeletal protein actin affects the conductance of
      amiloride-sensitive epithelial sodium channels (ENaC) was studied in planar lipid
      bilayers. In the presence of monomeric actin, we found a decrease in the single
      channel conductance of alpha-ENaC that did not occur when the internal [Ca2+]free
      was buffered to <10 nM. An analysis of single-channel kinetics demonstrated that
      Ca2+ induced the appearance of long-lived closed intervals separating bursts of
      channel activity, both in the presence and in the absence of actin. In the
      absence of actin, the duration of these bursts and the time spent by the channel
      in its open, but not in its short-lived closed state, were inversely proportional
      to [Ca2+]. This, together with a lengthening of the interburst intervals,
      translated into a dose-dependent decrease in the single-channel open probability.
      In contrast, a [Ca2+]-dependent decrease in alpha-ENaC conductance in the
      presence of actin was accompanied by lengthening of the burst intervals with no
      significant changes in the open or closed (both short- and long-lived) times. We
      conclude that Ca2+ acts as a "fast-to-intermediate" blocker when monomeric actin
      is present, producing a subsequent attenuation of the apparent unitary
      conductance of the channel.

PMID- 11325721
TI  - Structure of Na+,K+-ATPase at 11-A resolution: comparison with Ca2+-ATPase in E1
      and E2 states.
AB  - Na+,K+-ATPase is a heterodimer of alpha and beta subunits and a member of the P
      type ATPase family of ion pumps. Here we present an 11-A structure of the
      heterodimer determined from electron micrographs of unstained frozen-hydrated
      tubular crystals. For this reconstruction, the enzyme was isolated from
      supraorbital glands of salt-adapted ducks and was crystallized within the native
      membranes. Crystallization conditions fixed Na+,K+-ATPase in the vanadate
      inhibited E2 conformation, and the crystals had p1 symmetry. A large number of
      helical symmetries were observed, so a three-dimensional structure was calculated
      by averaging both Fourier-Bessel coefficients and real-space structures of data
      from the different symmetries. The resulting structure clearly reveals
      cytoplasmic, transmembrane, and extracellular regions of the molecule with
      densities separately attributable to alpha and beta subunits. The overall shape
      bears a remarkable resemblance to the E2 structure of rabbit sarcoplasmic
      reticulum Ca2+-ATPase. After aligning these two structures, atomic coordinates
      for Ca2+-ATPase were fit to Na+,K+-ATPase, and several flexible surface loops,
      which fit the map poorly, were associated with sequences that differ in the two
      pumps. Nevertheless, cytoplasmic domains were very similarly arranged, suggesting
      that the E2-to-E1 conformational change postulated for Ca2+-ATPase probably
      applies to Na+,K+-ATPase as well as other P-type ATPases.

PMID- 11325723
TI  - Inwardly rectifying current-voltage relationship of small-conductance Ca2+
      activated K+ channels rendered by intracellular divalent cation blockade.
AB  - Small conductance Ca2+-activated K+ channels (SK(Ca) channels) are a group of K+
      selective ion channels activated by submicromolar concentrations of intracellular
      Ca2+ independent of membrane voltages. We expressed a cloned SK(Ca) channel,
      rSK2, in Xenopus oocytes and investigated the effects of intracellular divalent
      cations on the current-voltage (I-V) relationship of the channels. Both Mg2+ and
      Ca2+ reduced the rSK2 channel currents in voltage-dependent manners from the
      intracellular side and thus rectified the I-V relationship at physiological
      concentration ranges. The apparent affinity of Mg2+ was changed as a function of
      both transmembrane voltage and intracellular Ca2+ concentration. Extracellular K+
      altered the voltage dependence as well as the apparent affinities of Mg2+ binding
      from intracellular side. Thus, the inwardly rectifying I-V relationship of SK(Ca)
      channels is likely due to the voltage-dependent blockade of intracellular
      divalent cations and that the binding site is located within the ion-conducting
      pathway. Therefore, intracellular Ca2+ modulates the permeation characteristics
      of SK(Ca) channels by altering the I-V relationship as well as activates the
      channel by interacting with the gating machinery, calmodulin, and SK(Ca) channels
      can be considered as Ca2+-activated inward rectifier K+ channels.

PMID- 11325722
TI  - Chemically charging the pore constriction opens the mechanosensitive channel
      MscL.
AB  - MscL is a bacterial mechanosensitive channel that protects the cell from osmotic
      downshock. We have previously shown that substitution of a residue that resides
      within the channel pore constriction, MscL's Gly-22, with all other 19 amino
      acids affects channel gating according to the hydrophobicity of the substitution
      (). Here, we first make a mild substitution, G22C, and then attach
      methanethiosulfonate (MTS) reagents to the cysteine under patch clamp. Binding
      MTS reagents that are positively charged ([2-(trimethylammonium)ethyl]
      methanethiosulfonate and 2-aminoethyl methanethiosulfonate) or negatively charged
      (sodium (2-sulfonatoethyl)methanethiosulfonate) causes MscL to gate
      spontaneously, even when no tension is applied. In contrast, the polar 2
      hydroxyethyl methanethiosulfonate halves the threshold, and the hydrophobic
      methyl methanethiolsulfonate increases the threshold. These observations indicate
      that residue 22 is in a hydrophobic environment before gating and in a
      hydrophilic environment during opening to a substate, a finding consistent with
      our previous study. In addition, we have found that cysteine 22 is accessible to
      reagents from the cytoplasmic side only when the channel is opened whereas it is
      accessible from the periplasmic side even in the closed state. These results
      support the view that exposure of hydrophobic surfaces to a hydrophilic
      environment during channel opening serves as the barrier to gating.

PMID- 11325724
TI  - Revisiting the role of Ca2+ in Shaker K+ channel gating.
AB  - Shaker K+ channels were expressed in outside-out macropatches excised from
      Xenopus oocytes, and the effects on gating of removal of extracellular Ca2+ were
      examined in the complete absence of intracellular divalent cations. Removal of
      extracellular Ca2+ by perfusion with EDTA-containing solution caused a small
      negative shift in the channel's voltage-activation curve and led to an increased
      nonselective leak, but did not otherwise alter or disrupt the channels. The
      results contradict the proposal that Ca2+ is an essential component required for
      maintenance of ion selectivity and proper gating of Kv-type K+ channels. The
      large nonselective leak in Ca2+-free conditions was found to be a patch-seal
      phenomenon related to F- ion in the recording pipette.

PMID- 11325726
TI  - Voltage clamp limitations of dual whole-cell gap junction current and voltage
      recordings. I. Conductance measurements.
AB  - Previous correction methods for series access resistance errors in the dual whole
      cell configuration did not take into account the effect of nonzero resting
      potentials (E(rest)) and junctional reversal potentials (E(rev)). Dual whole-cell
      currents were modeled according to resistor-circuit analysis and two correction
      formulas for the measurement of junctional currents (I(j)) were assessed. The
      equations for I(j), derived from Kirchoff's law before and after baseline
      subtraction of the nonjunctional current, were assessed for accuracy under a
      variety of whole-cell patch-clamp recording conditions. Both equations accurately
      correct for dual whole-cell voltage-clamp errors provided that the cellular
      parameters are included in the nonbaseline subtracted I(j) derivations.
      Junctional conductance (g(j)) estimates are most reliable at high junctional
      resistance (R(j)) values and minimize the need for corrective methods based on
      electrode series and cellular input resistances (R(el) and R(in)). In the "open
      cell" configuration, low R(j) values relative to R(in) are required for accurate
      g(j) estimates. These methods provide the basis for accurate quantitative
      measurements of junctional resistance (or conductance) of gap junction channels
      or connexin hemichannels in the dual whole-cell or open-cell configurations.
      Revaluation of V(j)-dependent gating of rat connexin40 g(j) produced nearly
      identical Boltzmann fits to previously published data. Continuous g(j)-V(j)
      curves generated by variable slope V(j) ramps provide for more accurate fits and
      assessment of the time-dependence of the half-inactivation voltage and net gating
      charge movement.

PMID- 11325725
TI  - A single residue differentiates between human cardiac and skeletal muscle Na+
      channel slow inactivation.
AB  - Slow inactivation determines the availability of voltage-gated sodium channels
      during prolonged depolarization. Slow inactivation in hNa(V)1.4 channels occurs
      with a higher probability than hNa(V)1.5 sodium channels; however, the precise
      molecular mechanism for this difference remains unclear. Using the macropatch
      technique we show that the DII S5-S6 p-region uniquely confers the probability of
      slow inactivation from parental hNa(V)1.5 and hNa(V)1.4 channels into chimerical
      constructs expressed in Xenopus oocytes. Site-directed mutagenesis was used to
      test whether a specific region within DII S5-S6 controls the probability of slow
      inactivation. We found that substituting V754 in hNa(V)1.4 with isoleucine from
      the corresponding position (891) in hNa(V)1.5 produced steady-state slow
      inactivation statistically indistinguishable from that in wild-type hNa(V)1.5
      channels, whereas other mutations have little or no effect on slow inactivation.
      This result indicates that residues V754 in hNa(V)1.4 and I891in hNa(V)1.5 are
      unique in determining the probability of slow inactivation characteristic of
      these isoforms. Exchanging S5-S6 linkers between hNa(V)1.4 and hNa(V)1.5 channels
      had no consistent effect on the voltage-dependent slow time inactivation
      constants [tau(V)]. This suggests that the molecular structures regulating rates
      of entry into and exit from the slow inactivated state are different from those
      controlling the steady-state probability and reside outside the p-regions.

PMID- 11325727
TI  - Hydration state of single cytochrome c monolayers on soft interfaces via neutron
      interferometry.
AB  - Yeast cytochrome c (YCC) can be covalently tethered to, and thereby vectorially
      oriented on, the soft surface of a mixed endgroup (e.g., -CH3/-SH = 6:1, or -OH/
      SH = 6:1) organic self-assembled monolayer (SAM) chemisorbed on the surface of a
      silicon substrate utilizing a disulfide linkage between its unique surface
      cysteine residue and a thiol endgroup. Neutron reflectivities from such
      monolayers of YCC on Fe/Si or Fe/Au/Si multilayer substrates with H2O versus D2O
      hydrating the protein monolayer at 88% relative humidity for the nonpolar SAM (
      CH3/-SH = 6:1 mixed endgroups) surface and 81% for the uncharged-polar SAM (-OH/
      SH = 6:1mixed endgroups) surface were collected on the NG1 reflectometer at NIST.
      These data were analyzed using a new interferometric phasing method employing the
      neutron scattering contrast between the Si and Fe layers in a single reference
      multilayer structure and a constrained refinement approach utilizing the finite
      extent of the gradient of the profile structures for the systems. This provided
      the water distribution profiles for the two tethered protein monolayers
      consistent with their electron density profile determined previously via x-ray
      interferometry (Chupa et al., 1994).

PMID- 11325728
TI  - Effects of lung surfactant proteins, SP-B and SP-C, and palmitic acid on
      monolayer stability.
AB  - Langmuir isotherms and fluorescence and atomic force microscopy images of
      synthetic model lung surfactants were used to determine the influence of palmitic
      acid and synthetic peptides based on the surfactant-specific proteins SP-B and SP
      C on the morphology and function of surfactant monolayers. Lung surfactant
      specific protein SP-C and peptides based on SP-C eliminate the loss to the
      subphase of unsaturated lipids necessary for good adsorption and respreading by
      inducing a transition between monolayers and multilayers within the fluid phase
      domains of the monolayer. The morphology and thickness of the multilayer phase
      depends on the lipid composition of the monolayer and the concentration of SP-C
      or SP-C peptide. Lung surfactant protein SP-B and peptides based on SP-B induce a
      reversible folding transition at monolayer collapse that allows all components of
      surfactant to be retained at the interface during respreading. Supplementing
      Survanta, a clinically used replacement lung surfactant, with a peptide based on
      the first 25 amino acids of SP-B also induces a similar folding transition at
      monolayer collapse. Palmitic acid makes the monolayer rigid at low surface
      tension and fluid at high surface tension and modifies SP-C function. Identifying
      the function of lung surfactant proteins and lipids is essential to the rational
      design of replacement surfactants for treatment of respiratory distress syndrome.

PMID- 11325729
TI  - Interaction of alpha-melanocyte stimulating hormone with binary phospholipid
      membranes: structural changes and relevance of phase behavior.
AB  - The interaction of alpha-melanocyte stimulating hormone (alpha-MSH) with
      negatively charged binary membrane systems composed of either 1,2-dimyristoyl-sn
      glycero-3-phosphocholine/1,2-dimyristoyl-sn-glycero-3-[phospho-rac-(1-glycerol)],
      (DMPC/DMPG) or DMPC/1,2-dimyristoyl-sn-glycero-3-phosphate (DMPC/DMPA), both at a
      3:1 ratio, was studied using complementary techniques (differential scanning
      calorimetry, infrared and ultraviolet absorption spectroscopy, and steady-state
      and time-resolved fluorescence). The peptide structure in buffer, at medium to
      high concentrations, is a mixture of aggregated beta-strands and random coil, and
      upon increasing the temperature the random coil configuration becomes
      predominant. At low concentrations (micromolar) there are essentially no
      aggregates. When in interaction with the lipidic systems this transition is
      prevented and the peptide is stabilized in a specific conformation different from
      the one in solution. The incorporation of alpha-MSH into phosphatidic acid
      containing systems produced a significant alteration of the calorimetric data.
      Lateral heterogeneity can be induced by the peptide in the DMPA-containing
      mixture, at variance with the one of DMPG. In addition, the lipid/water partition
      coefficient for the peptide in the presence of DMPC/DMPA is greater in the gel
      phase as compared to the fluid phase. From the high values of limiting
      anisotropies it can be concluded that the peptide presents a very reduced
      rotational dynamics when in interaction with the lipids, pointing out to a strong
      interaction. Overall, these results show that the structure and stability of
      alpha-MSH in a negatively charged membrane environment are substantially
      different from those of the peptide in solution, being stabilized in a specific
      conformation that could be important to eliciting its biological activity.

PMID- 11325730
TI  - Breaking the Meyer-Overton rule: predicted effects of varying stiffness and
      interfacial activity on the intrinsic potency of anesthetics.
AB  - Exceptions to the Meyer-Overton rule are commonly cited as evidence against
      indirect, membrane-mediated mechanisms of general anesthesia. However, another
      interpretation is possible within the context of an indirect mechanism in which
      solubilization of an anesthetic in the membrane causes a redistribution of
      lateral pressures in the membrane, which in turn shifts the conformational
      equilibrium of membrane proteins such as ligand-gated ion channels. It is
      suggested that compounds of different stiffness and interfacial activity have
      different intrinsic potencies, i.e., they cause widely different redistributions
      of the pressure profile (and thus different effects on protein conformational
      equilibria) per unit concentration of the compound in the membrane. Calculations
      incorporating the greater stiffness of perfluoromethylenic chains and the large
      interfacial attraction of hydroxyl groups predict the higher intrinsic potency of
      short alkanols than alkanes, the cutoffs in potency of alkanes and alkanols and
      the much shorter cutoffs for their perfluorinated analogues. Both effects,
      increased stiffness and interfacial activity, are present in unsaturated
      hydrocarbon solutes, and the intrinsic potencies are predicted to depend on the
      magnitude of both effects and on the number and locations of multiple bonds
      within the molecule. Most importantly, the intrinsic potencies of polymeric
      alkanols with regularly spaced hydroxyl groups are predicted to rise with
      increasing chain length, without cutoff; such molecules should serve to
      distinguish unambiguously between indirect mechanisms and direct binding
      mechanisms of anesthesia.

PMID- 11325731
TI  - Microelectrophoresis of a bilayer-coated silica bead in an optical trap:
      application to enzymology.
AB  - We describe an apparatus that combines microelectrophoresis and laser trap
      technologies to monitor the activity of phosphoinositide-specific phospholipase C
      delta1 (PLC-delta) on a single bilayer-coated silica bead with a time resolution
      of approximately 1 s. A 1-microm-diameter bead was coated with a phospholipid
      bilayer composed of electrically neutral phosphatidylcholine (PC) and negatively
      charged phosphatidylinositol 4,5-bisphosphate (2% PIP2) and captured in a laser
      trap. When an AC field was applied (160 Hz, 20 V/cm), the electrophoretic force
      produced a displacement of the bead, Delta(x), from its equilibrium position in
      the trap; Delta(x), which was measured using a fast quadrant diode detector, is
      proportional to the zeta potential and thus to the number of PIP2 molecules on
      the outer leaflet (initially, approximately 10(5)). When a solution containing
      PLC-delta flows past the bead, the enzyme adsorbs to the surface and hydrolyzes
      PIP2 to form the neutral lipid diacylglycerol. We observed a nonexponential decay
      of PIP2 on the bead with time that is consistent with a model based on the known
      structural properties of PLC-delta.

PMID- 11325732
TI  - Spontaneous entrapment of polynucleotides upon electrostatic interaction with
      ethanol-destabilized cationic liposomes.
AB  - This study describes the effect of ethanol and the presence of poly(ethylene)
      glycol (PEG) lipids on the interaction of nucleotide-based polyelectrolytes with
      cationic liposomes. It is shown that preformed large unilamellar vesicles (LUVs)
      containing a cationic lipid and a PEG coating can be induced to entrap
      polynucleotides such as antisense oligonucleotides and plasmid DNA in the
      presence of ethanol. The interaction of the cationic liposomes with the
      polynucleotides leads to the formation of multilamellar liposomes ranging in size
      from 70 to 120 nm, only slightly bigger than the parent LUVs from which they
      originated. The degree of lamellarity as well as the size and polydispersity of
      the liposomes formed increases with increasing polynucleotide-to-lipid ratio. A
      direct correlation between the entrapment efficiency and the membrane
      destabilizing effect of ethanol was observed. Although the morphology of the
      liposomes is still preserved at the ethanol concentrations used for entrapment
      (25-40%, v/v), entrapped low-molecular-weight solutes leak rapidly. In addition,
      lipids can flip-flop across the membrane and exchange rapidly between liposomes.
      Furthermore, there are indications that the interaction of the polynucleotides
      with the cationic liposomes in ethanol leads to formation of polynucleotide
      cationic lipid domains, which act as adhesion points between liposomes. It is
      suggested that the spreading of this contact area leads to expulsion of PEG
      ceramide and triggers processes that result in the formation of multilamellar
      systems with internalized polynucleotides. The high entrapment efficiencies
      achieved at high polyelectrolyte-to-lipid ratios and the small size and neutral
      character of these novel liposomal systems are of utility for liposomal delivery
      of macromolecular drugs.

PMID- 11325733
TI  - Membrane properties of D-erythro-N-acyl sphingomyelins and their corresponding
      dihydro species.
AB  - We have prepared acyl chain-defined D-erythro-sphingomyelins and D-erythro
      dihydrosphingomyelins and compared their properties in monolayer and bilayer
      membranes. Surface pressure/molecular area isotherms of D-erythro-N-16:0
      sphingomyelin (16:0-SM) and D-erythro-N-16:0-dihydrosphingomyelin (16:0-DHSM)
      show very similar packing properties, except that the expanded-to-condensed phase
      transition (crystallization) occurs at a lower surface pressure for 16:0-DHSM.
      The measured surface potential was generally about 100 mV less for 16:0-DHSM
      monolayers compared to 16:0-SM monolayers. The condensed domains (crystals) that
      formed in 16:0-SM monolayers as a function of compression displayed star-shaped
      morphology when viewed under an epifluorescence microscope. 16:0-DHSM monolayers
      did not form similar crystals upon compression. 16:0-DHSM was degraded much
      faster by sphingomyelinase from Staphylococcus aureus than 16:0-SM (10-fold
      difference in enzyme activity needed for comparable hydrolytic rate). Cholesterol
      desorption from 16:0-DHSM to cyclodextrin was slightly slower (approximately 20%)
      than the rate measured from 16:0-SM monolayers (at 60 mol % cholesterol). The
      bilayer melting temperature of 16:0-DHSM was 47.7 degrees C (DeltaH 8.3 kcal/mol)
      whereas it was 41.2 degrees C for 16:0-SM (DeltaH 8.1 kcal/mol). Cholesterol/16:0
      DHSM bilayers (15 mol % sterol) had more condensed domains than comparable 16:0
      SM bilayers, as evidenced from the quenching resistance of DPH in DHSM membranes.
      We conclude that cholesterol interacts more favorably with 16:0-DHSM and that the
      membranes are more condensed than comparable 16:0-SM-containing membranes.

PMID- 11325734
TI  - Theoretical kinetic studies of models for binding myosin subfragment-1 to
      regulated actin: Hill model versus Geeves model.
AB  - It was previously shown that a one-dimensional Ising model could successfully
      simulate the equilibrium binding of myosin S1 to regulated actin filaments (T. L.
      Hill, E. Eisenberg and L. Greene, Proc. Natl. Acad. Sci. U.S.A. 77:3186-3190,
      1980). However, the time course of myosin S1 binding to regulated actin was
      thought to be incompatible with this model, and a three-state model was
      subsequently developed (D. F. McKillop and M. A. Geeves, Biophys. J. 65:693-701,
      1993). A quantitative analysis of the predicted time course of myosin S1 binding
      to regulated actin, however, was never done for either model. Here we present the
      procedure for the theoretical evaluation of the time course of myosin S1 binding
      for both models and then show that 1) the Hill model can predict the "lag" in the
      binding of myosin S1 to regulated actin that is observed in the absence of Ca++
      when S1 is in excess of actin, and 2) both models generate very similar families
      of binding curves when [S1]/[actin] is varied. This result shows that, just based
      on the equilibrium and pre-steady-state kinetic binding data alone, it is not
      possible to differentiate between the two models. Thus, the model of Hill et al.
      cannot be ruled out on the basis of existing pre-steady-state and equilibrium
      binding data. Physical mechanisms underlying the generation of the lag in the
      Hill model are discussed.

PMID- 11325735
TI  - Conformational analysis of DNA-trinucleotide-hairpin-loop structures using a
      continuum solvent model.
AB  - A number of trinucleotide sequences in DNA can form compact and stable hairpin
      loops that may have significance for DNA replication and transcription. The
      conformational analysis of these motifs is important for an understanding of the
      function and design of nucleic acid structures. Extensive conformational searches
      have been performed on three experimentally known trinucleotide hairpin loops
      (AGC, AAA, and GCA) closed by a four-base-pair stem. An implicit solvation model
      based on the generalized Born method has been employed during energy minimization
      and conformational search. In addition, energy-minimized conformers were
      evaluated using a finite-difference Poisson-Boltzmann approach. For all three
      loop sequences, conformations close to experiment were found as lowest-energy
      structures among several thousand alternative energy minima. The inclusion of
      reaction-field contributions was found to be important for a realistic conformer
      ranking. Most generated hairpin loop structures within approximately 5 kcal x
      mol(-1) of the lowest-energy structure have a similar topology. Structures within
      approximately 10 kcal x mol(-1) could be classified into about five structural
      families representing distinct arrangements of loop nucleotides. Although a large
      number of backbone torsion angle combinations were compatible with each
      structural class, some specific patterns could be identified. Harmonic mode
      analysis was used to account for differences in conformational flexibility of low
      energy sub-states. Class-specific differences in the pattern of atomic
      fluctuations along the sequence were observed; however, inclusion of
      conformational entropy contributions did not change ranking of structural
      classes. For an additional loop sequence (AAG) with no available experimental
      structure, the approach suggests a lowest-energy loop topology overall similar to
      the other three loop sequences but closed by a different non-canonical base
      pairing scheme.

PMID- 11325736
TI  - Biophysical studies on the RNA cores of satellite tobacco mosaic virus.
AB  - Satellite tobacco mosaic virus (STMV) was probed using a variety of proteases.
      Consequences of the degradation were analyzed using gel electrophoresis, quasi
      elastic light scattering (QELS), and atomic force microscopy (AFM). Proteolysis
      rates of 30 minutes for complete degradation of the protein capsid, up to many
      hours, were investigated. With each protease, degradation of virions 17 nm in
      diameter was shown by QELS to result in particles of 10 nm diameter, which is
      that of the RNA core observed in the virion by x-ray diffraction analysis. This
      was verified by direct visualization with atomic force microscopy. Using QELS, it
      was further shown that freshly prepared RNA cores remain as individual, stable,
      10-nm condensed particles for 12 to 24 h. Clusters of particles then formed,
      followed by very large aggregates of 500 to 1000 nm diameter. AFM showed that the
      aggregates were composed of groups of the condensed RNA cores and were not due to
      unfolding of the nucleic acid. No unfolding of the core particles into extended
      conformation was seen by AFM until the samples were heated well beyond 90 degrees
      C. Mass spectrometry of RNA core particles revealed the presence of a major
      polypeptide whose amino acid sequence corresponded to residues 2 through 25 of
      the coat protein. Amino acids 13 through 25 were previously observed to be in
      direct contact with the RNA and are presumably protected from protease digestion.
      Low resolution difference Fourier analyses indicated the courses of the
      remainders of the amino terminal strands (amino acids 2-12) in intact virions.
      Any individual strand appears to have several choices of path, which accounts for
      the observed disorder at high resolution. These positively charged strands,
      serving as virtual polyamines, engage the helical segments of RNA. The intimate
      association of amino acid residues 2 through 25 with RNA likely contributes to
      the stability of the condensed conformation of the nucleic acid cores.

PMID- 11325737
TI  - Heme photolysis occurs by ultrafast excited state metal-to-ring charge transfer.
AB  - Ultrafast time-resolved resonance Raman spectra of carbonmonoxy hemoglobin (Hb),
      nitroxy Hb, and deoxy Hb are compared to determine excited state decay mechanisms
      for both ligated and unligated hemes. Transient absorption and Raman data provide
      evidence for a sequential photophysical relaxation pathway common to both ligated
      and unligated forms of Hb* (photolyzed heme), in which the excited state 1Q
      decays sequentially: 1Q-->Hb*I-->Hb*II-->Hb ground state. Consistent with the
      observed kinetics, the lifetimes of these states are <50 fs, approximately 300
      fs, and approximately 3 ps for 1Q, Hb*I, and Hb*II, respectively. The transient
      absorption data support the hypothesis that the Hb*I state results from an
      ultrafast iron-to-porphyrin ring charge transfer process. The Hb*II state arises
      from porphyrin ring-to-iron back charge transfer to produce a porphyrin ground
      state configuration a nonequilibrium iron d-orbital population. Equatorial d-pi*
      back-bonding of the heme iron to the porphyrin during the lifetime of the Hb*II
      state accounts for the time-resolved resonance Raman shifts on the approximately
      3 ps time scale. The proposed photophysical pathway suggests that iron-to-ring
      charge transfer is the key event in the mechanism of photolysis of diatomic
      ligands following a porphyrin ring pi-pi* transition.

PMID- 11325738
TI  - Roles of cytoplasmic arginine and threonine in chloride transport by the
      bacteriorhodopsin mutant D85T.
AB  - In the light-driven anion pump halorhodopsin (HR), the residues arginine 200 and
      threonine 203 are involved in anion release at the cytoplasmic side of the
      membrane. Because of large sequence homology and great structural similarities
      between HR and bacteriorhodopsin (BR), it has been suggested that anion
      translocation by HR and by the chloride-pumping BR mutant BR-D85T occurs by the
      same mechanism. Consequently, the functions of the R200/T203 pair in HR should be
      the same as those of the corresponding pair in BR-D85T (R175/T178). We have put
      this hypothesis to a test by creating two mutants of BR-D85T in which R175 and
      T178 were replaced by glutamine and valine, respectively. Chloride transport
      activities were essentially the same for all three mutants, whereas chloride
      binding and the kinetics of parts of the photocycle were markedly affected by the
      replacement of T178. In contrast, the consequences of mutating R175 proved to be
      less significant. These findings are consistent with evidence obtained on HR and
      therefore support the idea that the respective mechanistic roles of the
      cytoplasmic arginine/threonine pairs in HR and BR-D85T are equal.

PMID- 11325739
TI  - Autofluorescent proteins in single-molecule research: applications to live cell
      imaging microscopy.
AB  - The spectral and photophysical characteristics of the autofluorescent proteins
      were analyzed and compared to flavinoids to test their applicability for single
      molecule microscopy in live cells. We compare 1) the number of photons emitted by
      individual autofluorescent proteins in artificial and in vivo situations, 2) the
      saturation intensities of the various autofluorescent proteins, and 3) the
      maximal emitted photons from individual fluorophores in order to specify their
      use for repetitive imaging and dynamical analysis. It is found that under
      relevant conditions and for millisecond integration periods, the autofluorescent
      proteins have photon emission rates of approximately 3000 photons/ms (with the
      exception of DsRed), saturation intensities from 6 to 50 kW/cm2, and
      photobleaching yields from 10(-4) to 10(-5). Definition of a detection ratio led
      to the conclusion that the yellow-fluorescent protein mutant eYFP is superior
      compared to all the fluorescent proteins for single-molecule studies in vivo.
      This finding was subsequently used for demonstration of the applicability of eYFP
      in biophysical research. From tracking the lateral and rotational diffusion of
      eYFP in artificial material, and when bound to membranes of live cells, eYFP is
      found to dynamically track the entity to which it is anchored.

PMID- 11325740
TI  - Singlet-singlet annihilation kinetics in aggregates and trimers of LHCII.
AB  - Singlet-singlet annihilation experiments have been performed on trimeric and
      aggregated light-harvesting complex II (LHCII) using picosecond spectroscopy to
      study spatial equilibration times in LHCII preparations, complementing the large
      amount of data on spectral equilibration available in literature. The
      annihilation kinetics for trimers can well be described by a statistical
      approach, and an annihilation rate of (24 ps)(-1) is obtained. In contrast, the
      annihilation kinetics for aggregates can well be described by a kinetic approach
      over many hundreds of picoseconds, and it is shown that there is no clear
      distinction between inter- and intratrimer transfer of excitation energy. With
      this approach, an annihilation rate of (16 ps)(-1) is obtained after
      normalization of the annihilation rate per trimer. It is shown that the spatial
      equilibration in trimeric LHCII between chlorophyll a molecules occurs on a time
      scale that is an order of magnitude longer than in Photosystem I-core, after
      correcting for the different number of chlorophyll a molecules in both systems.
      The slow transfer in LHCII is possibly an important factor in determining
      excitation trapping in Photosystem II, because it contributes significantly to
      the overall trapping time.

PMID- 11325741
TI  - The conformation of serum albumin in solution: a combined phosphorescence
      depolarization-hydrodynamic modeling study.
AB  - There is a striking disparity between the heart-shaped structure of human serum
      albumin (HSA) observed in single crystals and the elongated ellipsoid model used
      for decades to interpret the protein solution hydrodynamics at neutral pH. These
      two contrasting views could be reconciled if the protein were flexible enough to
      change its conformation in solution from that found in the crystal. To
      investigate this possibility we recorded the rotational motions in real time of
      an erythrosin-bovine serum albumin complex (Er-BSA) over an extended time range,
      using phosphorescence depolarization techniques. These measurements are
      consistent with the absence of independent motions of large protein segments in
      solution, in the time range from nanoseconds to fractions of milliseconds, and
      give a single rotational correlation time phi(BSA, 1 cP, 20 degrees C) = 40 +/- 2
      ns. In addition, we report a detailed analysis of the protein hydrodynamics based
      on two bead-modeling methods. In the first, BSA was modeled as a triangular
      prismatic shell with optimized dimensions of 84 x 84 x 84 x 31.5 A, whereas in
      the second, the atomic-level structure of HSA obtained from crystallographic data
      was used to build a much more refined rough-shell model. In both cases, the
      predicted and experimental rotational diffusion rate and other hydrodynamic
      parameters were in good agreement. Therefore, the overall conformation in neutral
      solution of BSA, as of HSA, should be rigid, in the sense indicated above, and
      very similar to the heart-shaped structure observed in HSA crystals.

PMID- 11325742
TI  - Structural perturbations of azurin deposited on solid matrices as revealed by trp
      phosphorescence.
AB  - The phosphorescence emission of Cd-azurin from Pseudomonas aeruginosa was used as
      a probe of possible perturbations in the dynamical structure of the protein core
      that may be induced by protein-sorbent and protein-protein interactions occurring
      when the macromolecule is deposited into amorphous, thin solid films. Relative to
      the protein in aqueous solution, the spectrum is unrelaxed and the
      phosphorescence decay becomes highly heterogeneous, the average lifetime
      increasing sharply with film thickness and upon its dehydration. According to the
      lifetime parameter, adsorption of the protein to the substrate is found to
      produce a multiplicity of partially unfolded structures, an influence that
      propagates for several protein layers from the surface. Among the substrates used
      for film deposition, hydrophilic silica, dextran, DEAE-dextran, dextran sulfate,
      and hydrophobic octodecylamine, the perturbation is smallest with dextran sulfate
      and largest with octodecylamine. The destabilizing effect of protein-protein
      interactions, as monitored on 50-layer-thick films, is most evident at a relative
      humidity of 75%. Stabilizing agents were incorporated to attenuate the
      deleterious effects of protein aggregation. Among them, the most effective in
      preserving a more native-like structure are the disaccharides sucrose and
      trehalose in dry films and the polymer dextran in wet films. Interestingly, the
      polymer was found to achieve maximum efficacy at sensibly lower additive/protein
      ratios than the sugars.

PMID- 11325744
TI  - Image restoration for confocal microscopy: improving the limits of deconvolution,
      with application to the visualization of the mammalian hearing organ.
AB  - Deconvolution algorithms have proven very effective in conventional (wide-field)
      fluorescence microscopy. Their application to confocal microscopy is hampered, in
      biological experiments, by the presence of important levels of noise in the
      images and by the lack of a precise knowledge of the point spread function (PSF)
      of the system. We investigate the application of wavelet-based processing tools
      to deal with these problems, in particular wavelet denoising methods, which turn
      out to be very effective in application to three-dimensional confocal images.
      When used in combination with more classical deconvolution algorithms, these
      methods provide a robust and efficient restoration scheme allowing one to deal
      with difficult imaging conditions. To make our approach applicable in practical
      situations, we measured the PSF of a Biorad-MRC1024 confocal microscope under a
      large set of imaging conditions, including in situ acquisitions. As a specific
      biological application, we present several examples of restorations of three
      dimensional confocal images acquired inside an intact preparation of the hearing
      organ. We also provide a quantitative assessment of the gain in quality achieved
      by wavelet-aided restorations over classical deconvolution schemes, based on a
      set of numerical experiments that we performed with test images.

PMID- 11325743
TI  - Protein folding and function: the N-terminal fragment in adenylate kinase.
AB  - Three-dimensional protein folds range from simple to highly complex
      architectures. In complex folds, some building block fragments are more important
      for correct protein folding than others. Such fragments are typically buried in
      the protein core and mediate interactions between other fragments. Here we
      present an automated, surface area-based algorithm that is able to indicate
      which, among all local elements of the structure, is critical for the formation
      of the native fold, and apply it to structurally well-characterized proteins. In
      particular, we focus on adenylate kinase. The fragment containing the phosphate
      binding, P-loop (the "giant anion hole") flanked by a beta-strand and an alpha
      helix near the N-terminus, is identified as a critical building block. This
      building block shows a high degree of sequence and structural conservation in all
      adenylate kinases. The results of our molecular dynamics simulations are
      consistent with this identification. In its absence, the protein flips to a
      stable, non-native state. In this misfolded conformation, the other local
      elements of the structure are in their native-like conformations; however, their
      association is non-native. Furthermore, this element is critically important for
      the function of the enzyme, coupling folding, and function.

PMID- 11325745
TI  - Chemical force microscopy with active enzymes.
AB  - The adhesion forces have been measured between an atomic force microscope tip
      derivatized with an active enzyme, shikimate kinase, and an ATP mimic immobilized
      on a gold surface. Experiments with competitive binding of other ligands in
      solution show that the observed adhesion forces arise predominantly from specific
      interactions between the immobilized enzyme and surface-bound adenine derivative.
      These experiments represent a step in the development of a screening methodology
      based upon chemical force microscopy.

PMID- 11325746
TI  - Extraction of near-field fluorescence from composite signals to provide high
      resolution images of glial cells.
AB  - The subdiffraction optical resolution that can be achieved using near-field
      optical microscopy has the potential to permit new approaches and insights into
      subcellular function and molecular dynamics. Despite the potential of this
      technology, it has been difficult to apply to cellular samples. One significant
      problem is that sample thickness causes the optical information to be comprised
      of a composite signal containing both near- and far-field fluorescence. To
      overcome this issue we have developed an approach in which a near-field optical
      fiber is translated toward the cell surface. The increase in fluorescence
      intensity during z-translation contains two components: a far-field fluorescence
      signal when the tip of the fiber is distant from the labeled cell, and combined
      near- and far-field fluorescence when the tip interacts with the cell surface. By
      fitting a regression curve to the far-field fluorescence intensity as the
      illumination aperture approaches the cell, it is possible to isolate near-field
      from far-field fluorescent signals. We demonstrate the ability to resolve actin
      filaments in chemically fixed, hydrated glial cells. A comparison of composite
      fluorescence signals with extracted near-field fluorescence demonstrates that
      this approach significantly increases the ability to detect subcellular
      structures at subdiffraction resolution.

PMID- 11325747
TI  - Magnetic resonance of a dextran-coated magnetic fluid intravenously administered
      in mice.
AB  - Magnetic resonance was used to investigate the kinetic disposition of magnetite
      nanoparticles (9.4 nm core diameter) from the blood circulation after intravenous
      injection of magnetite-based dextran-coated magnetic fluid in female Swiss mice.
      In the first 60 min the time-decay of the nanoparticle concentration in the blood
      circulation follows the one-exponential (one-compartment) model with a half-life
      of (6.9 +/- 0.7) min. The X-band spectra show a broad single line at g
      approximately 2, typical of nanomagnetic particles suspended in a nonmagnetic
      matrix. The resonance field shifts toward higher values as the particle
      concentration reduces, following two distinct regimes. At the higher
      concentration regime (above 10(14) cm(-3)) the particle-particle interaction
      responds for the nonlinear behavior, while at the lower concentration regime
      (below 10(14) cm(-3)) the particle-particle interaction is ruled out and the
      system recovers the linearity due to the demagnetizing field effect alone.

PMID- 11325748
TI  - Putting genetics in perspective.

PMID- 11325749
TI  - Genetics and developing countries.

PMID- 11325750
TI  - Pharmacogenetics.

PMID- 11325751
TI  - Preimplantation genetic diagnosis.

PMID- 11325752
TI  - The promise of human genetic databases.

PMID- 11325753
TI  - Drug companies withdraw law suit against South Africa.

PMID- 11325754
TI  - Drug company lobbyist joins Oxfam's cheap drugs campaign.

PMID- 11325756
TI  - Doctors demand immediate access to antiretroviral drugs in Africa.

PMID- 11325757
TI  - NHS introduces new patient safety agency.

PMID- 11325758
TI  - Government to introduce safer administration of cancer drugs after fatal error.

PMID- 11325759
TI  - Review of generic drugs industry to go ahead, says trade commission.

PMID- 11325760
TI  - Three views of genetics: the enthusiast, the visionary, and the sceptic.
      Interview by Tessa Richards.

PMID- 11325761
TI  - Milburn challenges NHS to exploit genetics revolution.

PMID- 11325762
TI  - UK genetics database plans revealed.

PMID- 11325763
TI  - Insurers will not use test results from research.

PMID- 11325764
TI  - Mortality over two centuries in large pedigree with familial
      hypercholesterolaemia: family tree mortality study.
AB  - OBJECTIVE: To estimate all cause mortality from untreated familial
      hypercholesterolaemia free from selection for coronary artery disease. DESIGN:
      Family tree mortality study. SETTING: Large pedigree in Netherlands traced back
      to a single pair of ancestors in the 19th century. SUBJECTS: All members of
      pedigree aged over 20 years with 0.5 probability of carrying a mutation for
      familial hypercholesterolaemia. MAIN OUTCOME MEASURE: All cause mortality.
      RESULTS: A total of 70 deaths took place among 250 people analysed for 6950
      person years. Mortality was not increased in carriers of the mutation during the
      19th and early 20th century; it rose after 1915, reached its maximum between 1935
      and 1964 (standardised mortality ratio 1.78, 95% confidence interval 1.13 to
      2.76; P=0.003), and fell thereafter. Mortality differed significantly between two
      branches of the pedigree (relative risk 3.26, 95% confidence interval 1.74 to
      6.11; P=0.001). CONCLUSIONS: Risk of death varies significantly among patients
      with familial hypercholesterolaemia. This large variability over time and between
      branches of the pedigree points to a strong interaction with environmental
      factors. Future research is required to identify patients with familial
      hypercholesterolaemia who are at extreme risk and need early and vigorous
      preventive measures.

PMID- 11325765
TI  - Value of family history in identifying women at risk of venous thromboembolism
      during oral contraception: observational study.

PMID- 11325766
TI  - Gestational impaired glucose tolerance does not increase perinatal mortality in a
      developing country: cohort study.

PMID- 11325768
TI  - The challenge of integrating genetic medicine into primary care.

PMID- 11325769
TI  - Science, medicine, and the future: Postgenomic technologies: hunting the genes
      for common disorders.

PMID- 11325770
TI  - Online medical genetics resources: a US perspective.

PMID- 11325771
TI  - Online medical genetics resources: a UK perspective.

PMID- 11325772
TI  - Evidence based case report: Advice about mammography for a young woman with a
      family history of breast cancer.

PMID- 11325773
TI  - ABC of hypertension: Blood pressure measurement. Part II-conventional
      sphygmomanometry: technique of auscultatory blood pressure measurement.

PMID- 11325774
TI  - Integrated regional genetic services: current and future provision.

PMID- 11325775
TI  - The complexities of predictive genetic testing.

PMID- 11325776
TI  - Genetic risk and behavioural change.

PMID- 11325787
TI  - Agonist and antagonist activities on human NPFF(2) receptors of the NPY ligands
      GR231118 and BIBP3226.
AB  - Neuropeptide FF (NPFF) is a part of a neurotransmitter system acting as a
      modulator of endogenous opioid functions. At this time, no non-peptide or peptide
      NPFF-antagonists have been discovered. Here, we demonstrate that Neuropeptide Y
      (NPY) ligands, in fact possess significant ability to interact with the human
      NPFF(2) receptors. NPY Y(1) antagonist BIBP3226 and mixed Y(1) antagonist/Y(4)
      agonist GR231118 are able to displace with low affinity, 50 -- 100 nM, the
      specific binding on NPFF receptors expressed in CHO cells as well as in rat
      dorsal spinal cord, an affinity however superior to those determined against
      Y(2), Y(4) or Y(5) receptors. Furthermore, BIBP3226 which is unable to inhibit
      the forskolin-stimulated cyclic AMP production mediated by NPFF(2) receptors,
      antagonizes the effect of NPFF, revealing the first antagonist of NPFF receptors.
      These properties of NPY ligands on Neuropeptide FF receptors must be considered
      when evaluating pharmacological activities of these drugs.

PMID- 11325788
TI  - The polycationic aminoglycosides modulate the vasoconstrictive effects of
      endothelin: relevance to cerebral vasospasm.
AB  - 1. The vasoactive peptide endothelin (ET) has been implicated in the pathogenesis
      of cerebral vasospasm following subarachnoid haemorrhage. In these studies we
      investigated the involvement of protein kinase C (PKC) in sustained
      vasoconstriction induced by ET-1 in canine cerebral arteries. We also examined
      the ability of the aminoglycoside antibiotics to reverse the effects mediated by
      ET-1 in canine cerebrovascular smooth muscle cells (CVSMC). 2. The ET(A) receptor
      antagonist, BQ-123, showed a competitive inhibition of the ET-1 responses. 3. The
      vasoconstrictor action of both ET-1 (0.5 nM) and phorbol myristate acetate (PMA)
      (160 nM) was reversed by a selective PKC inhibitor, Ro-32-0432. 4. In cerebral
      arteries precontracted with ET-1 the aminoglycosides caused a concentration
      dependent relaxation. The EC(50s) for the relaxation were as follows: 0.54+/
      0.05, 0.63+/-0.01, 1.88+/-0.46 and 2.3+/-0.92 mM for gentamicin, neomycin,
      streptomycin and kanamycin, respectively. 5. Gentamicin caused a concentration
      dependent decrease of the PMA-induced responses in calcium free medium. 6. PKC
      activity was elevated in CVSMC exposed to ET-1 (170%) and PMA (167%) for a period
      of time (60 min) corresponding to maximum tonic contraction induced by these
      agents in arterial rings. 7. The administration of the aminoglycosides to CVSMC,
      in concentrations corresponding to the EC(50s) from contractility studies,
      reduced the effects of both ET-1 and PMA on PKC activity to the levels not
      different from controls. 8. These results show that the aminoglycosides are able
      to inhibit sustained vasoconstriction induced by ET-1, an effect which is due, at
      least in part, to the inhibition of PKC.

PMID- 11325790
TI  - Endogenous opioids suppress activation of nociceptors by sub-nanomolar nicotine.
AB  - 1. Nicotine can activate primary afferent nociceptors, one result of which is to
      increase neurogenic plasma extravasation. In this study we have demonstrated a
      novel proinflammatory effect of sub-nanomolar nicotine, mediated by peripheral
      action at sensory neurons. This action is normally masked by adrenal medulla
      derived delta-opioid receptor agonists. 2. While neurogenic plasma extravasation
      in the knee joint of the rat was not increased by intra-articular perfusion of
      nicotine (10(-8) M), perfusion of nicotine, at concentrations as low as 10(-10)
      M, combined with naloxone to block opioid receptors (or naltrindole to block
      delta-opioid receptors) was able to enhance bradykinin-induced plasma
      extravasation. This pro-inflammatory effect of intra-articular nicotine was
      mimicked by subcutaneous nicotine which was abolished by intra-articularly
      administered hexamethonium, a nicotinic receptor antagonist. 3. Following
      denervation of the adrenal medulla, intra-articular nicotine, alone at 10(-8) M,
      enhanced plasma extravasation, which was no longer enhanced by naloxone. 4.
      Destruction of primary afferents by neonatal treatment with capsaicin or blockade
      of sensory neurotransmitter by neurokinin-1 receptor antagonist RP-87,580
      abolished the pro-inflammatory effect of nicotine. 5. The effect of nicotine we
      describe in promoting inflammation is exerted at extremely low concentrations and
      therefore could have relevance to smokers, patients receiving medicinal nicotine
      as therapy and even second-hand smokers. Since receptor mechanisms on peripheral
      terminals of nociceptors may also be present on central terminals, actions of the
      endogenous nicotinic agonist acetylcholine, at central terminals of primary
      afferents or at other sites in the central nervous system, may be similarly
      modulated by opioids.

PMID- 11325789
TI  - Regulation of prostacyclin and prostaglandin E(2) receptor mediated responses in
      adult rat dorsal root ganglion cells, in vitro.
AB  - 1. Primary cultures of adult rat dorsal root ganglia (DRG) were prepared to
      examine the properties of prostacyclin (IP) receptors and prostaglandin E(2) (EP)
      receptors in sensory neurones. 2. IP receptor agonists, cicaprost and iloprost,
      stimulated adenylyl cyclase activity with EC(50) values of 22 and 28 nM,
      respectively. Prostaglandin E(1) (PGE(1)) and prostaglandin E(2) (PGE(2)) were 7
      fold less potent than cicaprost and iloprost, with PGE(2) displaying a lower
      maximal response. 3. Adenylyl cyclase activation by iloprost, PGE(1) and PGE(2),
      but not by forskolin, was highly dependent on DRG cell density. Although the
      potency of iloprost and PGE(2) for stimulating adenylyl cyclase was unchanged,
      their maximal responses were significantly increased at low cell density. 4. Both
      IP and EP(2/4) receptors could be down-regulated by agonist pretreatment, however
      the presence of cyclo-oxygenase (COX) inhibitors did not prevent this apparent
      down-regulation of IP and EP(2/4) receptors at high DRG cell densities. 5.
      Stimulation of adenylyl cyclase by the neuropeptide calcitonin gene-related
      peptide was also decreased at high DRG cell density, whereas the responses to
      beta-adrenoceptor agonists were increased at high DRG cell density. 6. Addition
      of nerve growth factor (NGF), or the addition of anti-neurotrophin antibodies
      during the 5-day culture of DRG cells, had no effect on IP receptor-mediated
      responses. 7. These results indicate that G(s)-coupled receptors involved in
      nociception are regulated in a variable manner in adult rat sensory neurones, and
      that this cell density-dependent regulation may be agonist-independent for IP and
      EP(2/4) receptors.

PMID- 11325791
TI  - Mechanical effects of liriodenine on the left ventricular-arterial coupling in
      Wistar rats: pressure-stroke volume analysis.
AB  - 1. In a recent in vivo study, liriodenine, an aporphine alkaloid, has been
      identified as a prominent anti-arrhythmic agent that can prevent rats' sudden
      deaths, even at the dose as low as 10(-7) g kg(-1). The aim of this study was to
      determine whether liriodenine at its effective anti-arrhythmic dose of 10(-7) g
      kg(-1) had effects on the left ventricular (LV)-arterial coupling in Wistar rats.
      2. LV pressure and ascending aortic flow signals were recorded to construct the
      ventricular and arterial end-systolic pressure-stroke volume relationships to
      calculate LV end-systolic elastance (E(es)) and effective arterial volume
      elastance (E(a)), respectively. The optimal afterload (Q(load)) determined by the
      ratio of E(a) to E(es) was used to measure the optimality of energy transmission
      from the left ventricle to the arterial system. 3. Liriodenine at the dose of 10(
      7) g kg(-1) showed no significant changes in basal heart rate (HR), cardiac
      output (CO), LV end-systolic pressure (P(es)), E(a), E(es), and Q(load). 4. By
      contrast, liriodenine at the dose of 10(-6) g kg(-1) produced a significant fall
      of 2.0% in HR and a significant rise of 5.8% in CO, but no significant change in
      P(es). Moreover, liriodenine administration of 10(-6) g kg(-1) to rats
      significantly decreased E(es) by 8.5% and E(a) by 10.6%, but did not change
      Q(load). 5. We conclude that liriodenine at the dose of 10(-7) g kg(-1) has no
      effects on the mechanical properties of the heart and the vasculature and the
      matching condition for the left ventricle coupled to its vasculature in rats.
      Even at 10 times the effective anti-arrhythmic dose, liriodenine shows no effects
      on the efficiency of energy transferred from the left ventricle to the arterial
      system.

PMID- 11325792
TI  - Mobilization of rat stomach ECL-cell histamine in response to short- or long-term
      treatment with omeprazole and/or YF 476 studied by gastric submucosal
      microdialysis in conscious rats.
AB  - 1. Mobilization of histamine from the ECL cells was monitored by gastric
      submucosal microdialysis in conscious rats. The ECL cells are known to operate
      under gastrin control and the purpose of the present study was to examine their
      in situ response to short-term (12 h) as well as long-term (28 days)
      hypergastrinaemia, induced by treatment with the proton pump inhibitor
      omeprazole. 2. Hypergastrinaemia promptly raised the histamine concentration in
      the microdialysate. The effect was prevented by CCK(2) receptor blockade (YF476).
      On day 7 of omeprazole treatment the microdialysate histamine concentration
      reached a peak, five times higher than before treatment. Subsequently (14 and 28
      days), less histamine was mobilized. 3. Gastrin infusion (4 h) raised the
      microdialysate histamine concentration in a dose-dependent manner in fasted rats
      and freely fed rats and in rats treated with omeprazole for a week. However,
      while fasted and fed rats responded to low doses of gastrin, the omeprazole
      treated rats required large doses of gastrin to respond. 4. When the amount of
      histamine mobilized was related to the serum gastrin concentration the following
      EC(50) values could be calculated: fasted rats 2.3 x 10(-10) M, freely fed rats
      2.5 x 10(-10) M, omeprazole-treated rats 8.7 x 10(-10) M. The maximal histamine
      responses in the three groups were 18.4 pmol 4 h(-1)+/-0.8, 21.9 pmol 4 h(-1)+/
      1.2 and 68.0 pmol 4 h(-1)+/-3.5, respectively. 5. The results suggest that ECL
      cells, exposed to a high gastrin concentration for a week, respond with a shift
      in the receptor-ligand binding affinity from high to low. Apparently, CCK(2)
      receptors of the ECL cells are subject to dynamic changes with respect to ligand
      binding affinity.

PMID- 11325793
TI  - Mutation screening of the muscarinic M(2) and M(3) receptor genes in normal and
      asthmatic subjects.
AB  - 1. Muscarinic receptors are important in the development of airway
      hyperresponsiveness, and dysfunction of these receptors has been suggested to be
      present in asthma. 2. The human muscarinic M(2) and M(3) receptor genes were
      screened for polymorphic variation using single-stranded conformation
      polymorphism (SSCP) analysis, complemented by direct fluorescent sequencing.
      Forty-six random DNA samples and 46 respiratory physician diagnosed asthmatic
      samples were used as a template for analysis. 3. Within the muscarinic M(2)
      receptor gene, we identified two degenerate single base substitutions (1197T-->C,
      Thr-->Thr and 976A-->C, Arg-->Arg) in one random and one asthmatic sample
      respectively. Analysis of the 3' UTR region revealed an additional 'A' at bp 1793
      (c.f. ATG). This was present in all of 49 samples analysed by sequencing or BsmI
      digest, suggesting that the published sequence (GenBank Accession NO: M16404) is
      incorrect. A common 3' UTR polymorphism (T-->A) was found at bp 1696 (c.f. ATG)
      (allelic frequency=65%, n=60), but this does not alter transcription factor
      recognition sites. 4. We were unable to identify any polymorphic variation within
      the muscarinic M(3) coding region or the flanking regions investigated, using the
      methods described. 5. The coding regions for the human muscarinic M(2) and M(3)
      receptor genes are both highly conserved. These data suggest that polymorphic
      variation within these coding sequences is unlikely to account for inter
      individual variability in response to methacholine or anticholinergic therapy.
      The potential functional significance of the muscarinic M(2) receptor 3' UTR
      polymorphism (bp 1696) remains to be determined.

PMID- 11325794
TI  - The biphasic immunoregulation of pyrimidylpiperazine (Y-40138) is IL-10 sensitive
      and requires NF-kappa B targeting in the alveolar epithelium.
AB  - 1. Pyrimidylpiperazine (Y-40138), a synthetic derivative of N-[1-(4-([4
      (pyrimidin-2-yl)piperazin-1-yl]methyl)phenyl)cyclopropyl] acetamide, is a novel
      dual regulator of pro- and anti-inflammatory cytokines in vivo. The aim of the
      present study was to determine the signal transduction mechanisms implicated in
      vitro. 2. In alveolar epithelial cells, pre-treatment (30 min) with Y-40138
      reduced LPS-induced biosynthesis of IL-1 beta, IL-6 and TNF-alpha, an effect
      paralleled by up-regulating an anti-inflammatory counter-loop mediated through IL
      10. 3. This differential regulation of pro- and anti-inflammatory signals was
      accompanied by an inhibition of the nuclear localization of selective NF-kappa B
      subunits, particularly NF-kappa B(1) (p50), RelA (p65), the major transactivating
      member of the Rel family, RelB (p68) and c-Rel (p75). In addition, Y-40138
      blockaded, in a dose-dependent manner, the LPS-induced nuclear activation of NF
      kappa B. 4. Analysis of the upstream pathway involved in Y-40138-dependent
      retardation of LPS-induced NF-kappa B translocation/activation revealed the
      involvement of an I kappa B-alpha sensitive pathway. Pre-treatment with Y-40138
      ameliorated LPS-induced degradation of I kappa B-alpha in the cytosolic
      compartment and retarded its phosphorylation, suggesting the involvement of an
      upstream kinase. 5. Recombinant IL-10 (0 -- 10 ng ml(-1)) blockaded, in a dose
      dependent manner, LPS-induced biosynthesis of IL-1 beta, IL-6 and TNF-alpha.
      Furthermore, rhIL-10 reduced the DNA binding activity of NF-kappa B.
      Immunoneutralization of endogenous IL-10 by a polyclonal alpha IL-10 (5 microg
      ml(-1)) reversed the inhibitory effect of Y-40138 on pro-inflammatory cytokines
      and partially restored the DNA binding activity of NF-kappa B. 6. These results
      indicate that Y-40138 mediated dual immunoregulation of pro- and anti
      inflammatory cytokines is IL-10 sensitive and mediated through the I kappa B
      alpha/NF-kappa B signal transduction pathway.

PMID- 11325795
TI  - The role of alpha(1)-adrenoceptors and 5-HT(1A) receptors in the control of the
      micturition reflex in male anaesthetized rats.
AB  - 1. The effects of the alpha(1)-adrenoceptor antagonists doxazosin (0.1 -- 2 mg
      kg(-1)), RS-100329 (alpha(1A); 0.01 -- 1 mg kg(-1)), RS-513815 (Ro 151-3815,
      alpha(1B); 0.3 -- 3 mg kg(-1)) and BMY 7378 (alpha(1D); 0.1 -- 1 mg kg(-1)), the
      5-HT(1A) receptor agonist, 8-OH-DPAT (0.03 -- 0.3 mg kg(-1)) and antagonist WAY
      100635 (0.03 -- 0.3 mg kg(-1)) were investigated (i.v.) on the 'micturition
      reflex' in the urethane anaesthetized male rat. 2. Reflex-evoked urethra
      contractions were most sensitive to the inhibitory action of RS-100329, followed
      by doxazosin, BMY 7378 and WAY-100635 and then RS-513815. The maximum inhibition
      was 66, 63, 54, 46 and 22% at doses of 0.3, 0.5, 0.3, 0.3 and 3 mg kg(-1)
      respectively. 3. BMY 7378 and 8-OH-DPAT decreased, while WAY-100635 increased,
      the pressure threshold to induce bladder contraction. WAY-100635 (0.01 mg kg(-1))
      blocked the effects of BMY 7378 (1 mg kg(-1)) on bladder pressure and volume
      threshold. 4. Doxazosin, RS-100329 and BMY 7378 had a similar potency in inducing
      a fall in arterial blood pressure while WAY-100635 only caused a fall at the
      highest dose. 5. Therefore, reflex-evoked urethral contraction involves the
      activation of alpha(1A/1D)-adrenoceptors, as BMY 7378 and RS-100329 are similarly
      potent in attenuating this effect. The ability of WAY-100635 to attenuate this
      contraction may suggest that 5-HT(1A) receptors are also involved. However, as
      this inhibition occurred at the highest dose of WAY-100635, which also caused a
      fall in arterial blood pressure; this effect is considered to be due to blockade
      of alpha(1)-adrenoceptors not 5-HT(1A) receptors. Nevertheless the initiation of
      the 'micturition reflex' involves the activation of 5-HT(1A) receptors.

PMID- 11325796
TI  - Murine ventricular L-type Ca(2+) current is enhanced by zinterol via beta(1)
      adrenoceptors, and is reduced in TG4 mice overexpressing the human beta(2)
      adrenoceptor.
AB  - 1. The functional coupling of beta(2)-adrenoceptors (beta(2)-ARs) to murine L
      type Ca(2+) current (I(Ca(L))) was investigated with two different approaches.
      The beta(2)-AR signalling cascade was activated either with the beta(2)-AR
      selective agonist zinterol (myocytes from wild-type mice), or by spontaneously
      active, unoccupied beta(2)-ARs (myocytes from TG4 mice with 435 fold
      overexpression of human beta(2)-ARs). Ca(2+) and Ba(2+) currents were recorded in
      the whole-cell and cell-attached configuration of the patch-clamp technique,
      respectively. 2. Zinterol (10 microM) significantly increased I(Ca(L)) amplitude
      of wild-type myocytes by 19+/-5%, and this effect was markedly enhanced after
      inactivation of Gi-proteins with pertussis-toxin (PTX; 76+/-13% increase).
      However, the effect of zinterol was entirely mediated by the beta(1)-AR subtype,
      since it was blocked by the beta(1)-AR selective antagonist CGP 20712A (300 nM).
      The beta(2)-AR selective antagonist ICI 118,551 (50 nM) did not affect the
      response of I(Ca(L)) to zinterol. 3. In myocytes with beta(2)-AR overexpression
      I(Ca(L)) was not stimulated by the activated signalling cascade. On the contrary,
      I(Ca(L)) was lower in TG4 myocytes and a significant reduction of single-channel
      activity was identified as a reason for the lower whole-cell I(Ca(L)). The
      beta(2)-AR inverse agonist ICI 118,551 did not further decrease I(Ca(L)). PTX
      treatment increased current amplitude to values found in control myocytes. 4. In
      conclusion, there is no evidence for beta(2)-AR mediated increases of I(Ca(L)) in
      wild-type mouse ventricular myocytes. Inactivation of Gi-proteins does not unmask
      beta(2)-AR responses to zinterol, but augments beta(1)-AR mediated increases of
      I(Ca(L)). In the mouse model of beta(2)-AR overexpression I(Ca(L)) is reduced due
      to tonic activation of Gi-proteins.

PMID- 11325797
TI  - NK-104, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, reduces
      osteopontin expression by rat aortic smooth muscle cells.
AB  - 1. It has been suggested that osteopontin promotes the development of
      atherosclerosis, especially under diabetic conditions. 2. In the present study,
      we found that NK-104, a new potent synthetic inhibitor of 3-hydroxy-3
      methylglutaryl coenzyme A reductase, reduced osteopontin expression both at
      protein and mRNA levels in cultured rat aortic smooth muscle cells. 3. The
      inhibitory effect of NK-104 was almost completely reversed by mevalonate,
      suggesting that mevalonate or its metabolites play important roles in the
      regulation of osteopontin expression. 4. Furthermore, oral administration of NK
      104 (3 mg kg(-1) day(-1) for 7 days) effectively suppressed abnormally
      upregulated expression of osteopontin mRNA in the aorta and kidney of
      streptozotocin-induced diabetic rats. 5. These data support a notion that NK-104
      is a suitable drug for the treatment of diabetic patients with
      hypercholesterolaemia.

PMID- 11325798
TI  - Protection against beta-amyloid peptide toxicity in vivo with long-term
      administration of ferulic acid.
AB  - 1. beta-Amyloid peptide (A beta), a 39 -- 43 amino acid peptide, is believed to
      induce oxidative stress and inflammation in the brain, which are postulated to
      play important roles in the pathogenesis of Alzheimer's disease. Ferulic acid is
      an antioxidant and anti-inflammatory agent derived from plants; therefore, the
      potential protective activity of ferulic acid against A beta toxicity in vivo was
      examined. 2. Mice were allowed free access to drinking water (control) or water
      containing ferulic acid (0.006%). After 4 weeks, A beta 1-42 (410 pmol) was
      administered via intracerebroventricular injection. 3. Injection of control mice
      with A beta 1-42 impaired performance on the passive avoidance test (35% decrease
      in step-through latency), the Y-maze test (19% decrease in alternation
      behaviour), and the water maze test (32% decrease in percentage time in platform
      quadrant). In contrast, mice treated with ferulic acid prior to A beta 1-42
      administration were protected from these changes (9% decrease in step-through
      latency; no decrease in alternation behaviour; 14% decrease in percentage time in
      platform-quadrant). A beta 1-42 induced 31% decrease in acetylcholine level in
      the cortex, which was tended to be ameliorated by ferulic acid. 4. In addition, A
      beta 1-42 increased immunoreactivities of the astrocyte marker glial fibrillary
      acidic protein (GFAP) and interleukin-1 beta (IL-1 beta) in the hippocampus,
      effects also suppressed by pretreatment with ferulic acid. 5. Administration of
      ferulic acid per se unexpectedly induced a transient and slight increase in GFAP
      and IL-1 beta immunoreactivity in the hippocampus on day 14, which returned to
      basal levels on day 28. A slight (8%) decrease in alternation behaviour was
      observed on day 14. 6. These results demonstrate that long-term administration of
      ferulic acid induces resistance to A beta 1-42 toxicity in the brain, and suggest
      that ferulic acid may be a useful chemopreventive agent against Alzheimer's
      disease.

PMID- 11325799
TI  - Involvement of accumulated endogenous NOS inhibitors and decreased NOS activity
      in the impaired neurogenic relaxation of the rabbit proximal urethra with
      ischaemia.
AB  - 1. We examined the effect of ischaemia on the neurogenic and nitric oxide (NO)
      mediated urethral relaxation. 2. Rabbits were divided into control and urethral
      ischaemia (UI) groups, which was prepared by the partial occlusion of bilateral
      iliac arteries using blood vessel occluders. 3. Neurogenic and NO-mediated
      proximal urethral relaxation induced by electrical field stimulation (EFS) was
      greatly impaired in the UI group, while relaxation by sodium nitroprusside (SNP)
      as a NO donor showed no difference between the two groups. Pretreatment with L
      arginine significantly improved but did not normalize the impaired relaxation in
      the UI group. Not only basal level, but also stimulated production of cyclic GMP
      with EFS, were significantly decreased in the UI group. 4. The tissue contents of
      N(G)-methyl-L-arginine (L-NMA) and asymmetric N(G), N(G)-dimethyl-L-arginine
      (ADMA) in the proximal urethra were increased following ischaemia. While L
      arginine and symmetric N(G), N'(G)-dimethyl-L-arginine (SDMA) contents remained
      unchanged. Exogenously applied authentic L-NMA and ADMA (1 -- 100 microM)
      concentration-dependently inhibited the EFS-induced urethral relaxation in the
      control group. The inhibition with L-NMA and ADMA was undetectable in the
      presence of 3 mM L-arginine. 5. The Ca(2+)-dependent NOS activity in the urethra
      from the UI group was significantly lower than that from the control group and
      was not restored by an addition of 3 mM L-arginine. 6. These results suggest that
      the impaired neurogenic and NO-mediated urethral relaxation with ischaemia is
      closely related to the increased accumulation of L-NMA and ADMA and decreased NOS
      activity, which would result in an accelerated reduction in NO
      production/release.

PMID- 11325800
TI  - Neuromodulatory effect of propentofylline on rat brain under acute and long-term
      hypoperfusion.
AB  - 1. The effects of propentofylline (PPF, 25 mg kg(-1) body weight per day) on rat
      cerebral energy state and cytokine expression as well as on behaviour and
      histopathology were studied after acute and long-term permanent bilateral common
      carotid artery occlusion (BCCAO). 2. In the absence of PPF, acute ischaemia led
      to a decrease in energy-rich phosphates in parietotemporal cortex and hippocampus
      which correlated with an increase in AMP and adenosine concentrations measured by
      high-performance liquid chromatography technique. The concentrations of cortical
      cytokines TNF alpha and IL1 beta were increased 12 and 19 fold, respectively. 3.
      PPF had a neuroprotective action after 20 min of BCCAO, reducing the deleterious
      effect of acute ischaemia on rat brain energy state and microglial reaction.
      Simultaneously, PPF treatment increased cyclic-AMP 3 fold. 4. Three weeks of
      permanent BCCAO did not significantly disturb brain energy metabolism, microglial
      reaction or histopathology. However, a significant reduction of 30 -- 50% in rat
      memory capacities and a locomotor hyperactivity were obtained. 5. Continuous PPF
      application, however, led to a marked increase in rat working memory and to
      reduced locomotor activity, which were returned nearly to control levels by 1
      week after permanent BCCAO. In summary, PPF showed a clear neuroprotective effect
      on cerebral energy state and pro-inflammatory cytokines under conditions of acute
      global ischaemia. Continuous administration of PPF led to memory improvement
      during permanent BCCAO. 6. These results underscore the benefit of treatment with
      PPF in clinical practice, particularly during stroke, but also in cerebrovascular
      and neurodegenerative disorders.

PMID- 11325801
TI  - Antihypertensive effects of the flavonoid quercetin in spontaneously hypertensive
      rats.
AB  - 1. The effects of an oral daily dose (10 mg kg(-1)) of the flavonoid quercetin
      for 5 weeks in spontaneously hypertensive (SHR) and normotensive Wistar Kyoto
      rats (WKY) were analysed. 2. Quercetin induced a significant reduction in
      systolic (-18%), diastolic (-23%) and mean (-21%) arterial blood pressure and
      heart rate (-12%) in SHR but not in WKY rats. 3. The left ventricular weight
      index and the kidney weight index in vehicle-treated SHR were significantly
      greater than in control WKY and these parameters were significantly reduced in
      quercetin-treated SHR in parallel with the reduction in systolic blood pressure.
      4. Quercetin had no effect on the vasodilator responses to sodium nitroprusside
      or to the vasoconstrictor responses to noradrenaline or KCl but enhanced the
      endothelium-dependent relaxation to acetylcholine (E(max)=58+/-5% vs 78+/-5%,
      P<0.01) in isolated aortae. 5. The 24 h urinary isoprostane F(2 alpha) excretion
      and the plasma malonyldialdehyde (MDA) levels in SHR rats were increased as
      compared to WKY rats. However, in quercetin-treated SHR rats both parameters were
      similar to those of vehicle-treated WKY. 6. These data demonstrate that quercetin
      reduces the elevated blood pressure, the cardiac and renal hypertrophy and the
      functional vascular changes in SHR rats without effect on WKY. These effects were
      associated with a reduced oxidant status due to the antioxidant properties of the
      drug.

PMID- 11325802
TI  - The properties of ryanodine-sensitive Ca(2+) release in mouse gastric smooth
      muscle cells.
AB  - 1. Under voltage-clamped conditions, gastric smooth muscle cells of BALB/c mice
      developed spontaneous (STOCs) and caffeine- (I(CAF)) and carbachol-induced
      (I(CCh)) transient outward currents. 2. In fura-2 microscopic measurements of
      intracellular Ca(2+) concentration ([Ca(2+)](i)), caffeine and carbachol (CCh)
      provoked similar transient [Ca(2+)](i) elevations. 3. Both I(CCh) and CCh-induced
      [Ca(2+)](i) elevation of single smooth muscle cells occurred in an 'all-or
      nothing' fashion in contrast to the reproducible caffeine responses. 4. On the
      basis of the suppression of STOCs and I(CAF) by nicardipine, tetraethylammonium
      and iberiotoxin, but not by charybdotoxin nor apamin, it was suggested that both
      currents were generated by large conductance type Ca(2+)-activated K(+) channels.
      5. In measurements of isometric tension, caffeine produced relaxation of gastric
      smooth muscle strips in a concentration-dependent manner (0.1 -- 3 mM). The
      concentration-dependent relaxation with caffeine was mimicked by dibutyryl cyclic
      AMP which produced potentiation of contraction triggered by 50 mM KCL. 6. At
      caffeine concentrations >3 mM, a transient contraction followed by relaxation was
      provoked as the quasi maximal response to caffeine. In the quasi maximal
      response, caffeine acted as a potent relaxant in smooth muscle strips
      precontracted with 50 mM KCl or 3 microM CCh. 7. The relaxation with caffeine was
      significantly accelerated in those strips precontracted with KCl or CCh. All
      these results suggest that ryanodine-sensitive Ca(2+) release, which is triggered
      by caffeine, is an important modifier of Ca(2+) homeostasis in the cytoplasm and
      the contractility of gastric smooth muscle cells of mice.

PMID- 11325803
TI  - Functional characterization of a human receptor for neuropeptide FF and related
      peptides.
AB  - 1. Neuropeptides FF (NPFF) and AF (NPAF) are involved in pain modulation and
      opioid tolerance. These peptides were known to act through uncharacterized G
      protein-coupled receptors (GPCR). We describe here, using an aequorin-based assay
      as screening tool, that an orphan GPCR, previously designated HLWAR77, is a
      functional high affinity receptor for NPFF and related peptides. This receptor is
      further designated as NPFFR. 2. Binding experiments were performed with a new
      radioiodinated probe, [(125)I]-EYF, derived from the EFW-NPSF sequence of the rat
      NPFF precursor. Chinese hamster ovary (CHO) cell membranes expressing NPFFR bound
      [(125)I]-EYF with a K(d) of 0.06 nM. Various NPFF analogues and related peptides
      inhibited [(125)I]-EYF specific binding with the following rank order (K(i)):
      human NPAF (0.22 nM), SQA-NPFF (0.29 nM), NPFF (0.30 nM), 1DMe (0.31 nM), EYW
      NPSF (0.32 nM), QFW-NPSF (0.35 nM), 3D (1.12 nM), Met-enk-RF-NH(2) (3.25 nM),
      FMRF-NH(2) (10.5 nM) and NPSF (12.1 nM). 3. The stimulatory activity of the same
      set of peptides was measured by a functional assay based on the co-expression of
      NPFFR, G(alpha 16) and apoaequorin. The rank order of potency was consistent with
      the results of the binding assay. 4. Membranes from NPFFR expressing CHO cells
      bound GTP gamma[(35)S] in the presence of SQA-NPFF. This functional response was
      prevented by pertussis toxin treatment, demonstrating the involvement of G(i)
      family members. 5. SQA-NPFF inhibited forskolin induced cyclic AMP accumulation
      in recombinant CHO cells in a dose dependent manner. This response was abolished
      as well by pertussis toxin pre-treatment. 6. RT -- PCR analysis of human tissues
      mRNA revealed that expression of NPFFR was mainly detected in placenta, thymus
      and at lower levels in pituitary gland, spleen and testis.

PMID- 11325804
TI  - Role of bradykinin and eNOS in the anti-ischaemic effect of trandolapril.
AB  - 1. Angiotensin converting enzyme (ACE) inhibitors are under study in ischaemic
      heart diseases, their mechanism of action being still unknown. 2. The anti
      ischaemic effect of trandolapril and the possible involvement of a bradykinin
      modulation on endothelial constitutive nitric oxide synthase (eNOS) in exerting
      this effect, were investigated. 3. Three doses of trandolapril, chronically
      administered in vivo, were studied in isolated perfused rat hearts subjected to
      global ischaemia followed by reperfusion. 4. Trandolapril has an anti-ischaemic
      effect. The dose of 0.3 mg kg(-1) exerted the best effect reducing diastolic
      pressure increase during ischaemia (from 33.0+/-4.5 to 14.0+/-5.2 mmHg; P<0.05 vs
      control) and reperfusion (from 86.1+/-9.4 to 22.2+/-4.1 mmHg; P<0.01 vs control),
      improving functional recovery, counteracting creatine phosphokinase release and
      ameliorating energy metabolism after reperfusion. 5. Trandolapril down-regulated
      the baseline developed pressure. 6. Trandolapril increased myocardial bradykinin
      content (from 31.8+/-6.1 to 54.8+/-7.5 fmol/gww; P<0.05, at baseline) and eNOS
      expression and activity in aortic endothelium (both P<0.01 vs control) and in
      cardiac myocytes (from 11.3+/-1.5 to 17.0+/-2.0 mUOD microg protein(-1) and from
      0.62+/-0.05 to 0.80+/-0.06 pmol mg prot(-1) min(-1); both P<0.05 vs control). 7.
      HOE 140 (a bradykinin B(2) receptor antagonist) and NOS inhibitors counteracted
      the above-reported effects. 8. There was a negative correlation between myocyte's
      eNOS up-regulation and myocardial contraction down-regulation. 9. Our findings
      suggest that the down-regulation exerted by trandolapril on baseline cardiac
      contractility, through a bradykinin-mediated increase in NO production, plays a
      crucial role in the anti-ischaemic effect of trandolapril by reducing energy
      breakdown during ischaemia.

PMID- 11325805
TI  - Dual action of ZD6169, a novel K(+) channel opener, on ATP-sensitive K(+)
      channels in pig urethral myocytes.
AB  - 1. The effects of ZD6169, a novel K(+) channel opener, on both membrane and
      unitary currents in pig urethra were investigated using patch-clamp techniques.
      Its effect was also examined on currents in inside-out patches of COS7 cells
      expressing carboxy terminus truncated inwardly rectifying K(+) channel (Kir6.2)
      subunits (Kir6.2C36) which form ATP-sensitive K(+) channels (K(ATP) channels). 2.
      In current-clamp mode, ZD6169 (< or = 10 microM) induced a concentration
      dependent membrane hyperpolarization. Higher concentrations (> or = 30 microM)
      caused a transient membrane hyperpolarization, followed by a gradual membrane
      depolarization. On removal of ZD6169, an after hyperpolarization was observed. 3.
      In conventional voltage-clamp configuration, at -50 mV in symmetrical 140 mM K(+)
      conditions, ZD6169 (100 microM) caused a transient inward current which gradually
      decayed. Removal of ZD6169 evoked a much larger amplitude K(+) current with a
      similar time course. 4. ZD6169 produced an inward glibenclamide-sensitive K(+)
      current, demonstrating a bell-shaped concentration-response relationship. 5. In
      cell-attached configuration in symmetrical 140 mM K(+) conditions, ZD6169 (< or =
      30 microM) activated an K(ATP) channel which was reversibly suppressed by
      application of glibenclamide. In contrast, ZD6169 (100 microM) inhibited the
      activity of the levcromakalim-induced K(ATP) channels. 6. ZD6169 (100 microM) had
      no significant effect on the channel activity of Kir6.2C36 in inside-out
      configuration, although cibenzoline greatly suppressed the channel activity. 7.
      These results demonstrate that ZD6169 possesses a dual effect on the activity of
      the K(ATP) channel; activating at low concentration and inhibiting at higher
      concentration.

PMID- 11325806
TI  - Histamine H(3) receptor-mediated inhibition of depolarization-induced, dopamine
      D(1) receptor-dependent release of [(3)H]-gamma-aminobutryic acid from rat
      striatal slices.
AB  - 1. A study was made of the regulation of [(3)H]-gamma-aminobutyric acid ([(3)H]
      GABA) release from slices of rat striatum by endogenous dopamine and exogenous
      histamine and a histamine H(3)-agonist. Depolarization-induced release of [(3)H]
      GABA was Ca(2+)-dependent and was increased in the presence of the dopamine D(2)
      receptor family antagonist, sulpiride (10 microM). The sulpiride-potentiated
      release of [(3)H]-GABA was strongly inhibited by the dopamine D(1) receptor
      family antagonist, SCH 23390 (1 microM). Neither antagonist altered basal
      release. 2. The 15 mM K(+)-induced release of [(3)H]-GABA in the presence of
      sulpiride was inhibited by 100 microM histamine (mean inhibition 78+/-3%) and by
      the histamine H(3) receptor-selective agonist, immepip, 1 microM (mean inhibition
      81+/-5%). The IC(50) values for histamine and immepip were 1.3+/-0.2 microM and
      16+/-2 nM, respectively. The inhibitory effects of histamine and immepip were
      reversed by the H(3) receptor antagonist, thioperamide, 1 microM. 3. The
      inhibition of 15 mM K(+)-induced [(3)H]-GABA release by immepip was reversed by
      the H(3) receptor antagonist, clobenpropit, K(d) 0.11+/-0.04 nM. Clobenpropit
      alone had no effect on basal or stimulated release of [(3)H]-GABA. 4. Elevated
      K(+) caused little release of [(3)H]-GABA from striatal slices from reserpinized
      rats, unless the D(1) partial agonist, R(+)-SKF 38393, 1 microM, was also
      present. The stimulated release in the presence of SKF 38393 was reduced by 1
      microM immepip to the level obtained in the absence of SKF 38393. 5. These
      observations demonstrate that histamine H(3) receptor activation strongly
      inhibits the dopamine D(1) receptor-dependent release of [(3)H]-GABA from rat
      striatum; primarily through an interaction at the terminals of GABA neurones.

PMID- 11325807
TI  - Effects of yohimbine on the antinociceptive and place conditioning effects of
      opioid agonists in rodents.
AB  - 1. The pharmacological modulation of opioid actions by drugs acting on
      heterologous mechanisms could be useful to overcome some of the main problems
      associated with the use of opiate agonists. Based on previous findings on the
      interactions between yohimbine and opioid drugs, we have further studied the
      effects of yohimbine on the antinociceptive and positive-negative reinforcing
      effects of morphine (mu opioid receptor-preferring agonist), U-50,488 (kappa
      agonist) and SNC80 (delta agonist). 2. Pretreatment with yohimbine completely
      blocked the antinociception provided by the three opioid agonists in the mouse
      tail-immersion test. 3. A similar blockade of SNC80 and U-50,488-induced
      antinociception was observed with yohimbine in the mouse hot plate test at the
      same doses. In this paradigm, the effect of the kappa agonist was very slight and
      the actions of yohimbine rather variable. 4. In place conditioning experiments
      with SD (Sprague -- Dawley) male rats, yohimbine alone was inactive but it
      limited the preference induced by morphine and SNC80 and the aversive effect of U
      50,488. Impaired novelty preference was also observed with the combination of
      yohimbine and U-50,488. 5. It is concluded that yohimbine tends to limit opioid
      antinociception and the addictive potential of mu and delta opioid agonists. More
      selective drugs could help to understand the mechanisms involved in these
      actions.

PMID- 11325808
TI  - Enhancement of the effects of a complete inhibitor of enkephalin-catabolizing
      enzymes, RB 101, by a cholecystokinin-B receptor antagonist in diabetic rats.
AB  - 1. RB 101, a complete inhibitor of enkephalin-catabolizing enzymes, has been
      previously shown to produce antinociception in normal rats after systemic
      administration. Moreover, its coadministration with a cholecystokinin-B (CCK-B)
      receptor antagonist has been shown to strongly enhance its antinociceptive effect
      in normal rats. In this work, we determined whether RB 101 was able to reduce
      hyperalgesia and allodynia in diabetic rats, a model of neuropathic pain. The
      type of opioid receptors (mu or delta) involved was determined using naloxone and
      naltrindole, respectively, and the interactions between endogenous enkephalins
      and CCK on nociception control was investigated using coadministration of RB 101
      and the CCK-B receptor antagonist CI-988. 2. RB 101 suppressed mechanical
      hyperalgesia (paw pressure-induced vocalization test), partially alleviated
      mechanical allodynia (von Frey hair test), and was ineffective in thermal
      allodynia (tail immersion test). The analgesic effect was completely cancelled by
      naloxone or naltrindole, suggesting that is requires the availability of mu-
      and/or delta-opioid receptors. 3. The combination of an inactive dose of CI-988
      with the lowest effective dose of RB 101 resulted in a stronger increase in the
      vocalization threshold comparatively to RB 101 alone. 4. The present study
      demonstrates that the antinociception generated by RB 101 induced by elevation of
      extracellular levels of endogenous enkephalins, can be extended to neuropathic
      pain in diabetic rats and that blockade of CCK-B receptors potentiated
      antinociceptive effects elicited by RB 101.

PMID- 11325809
TI  - Effects of terbutaline on NGF formation in allergic inflammation of the rat.
AB  - 1. The aim of this study was to determine the effects of the beta adrenergic
      agonist terbutaline on NGF increase caused by allergic inflammation in rats. 2.
      Intraplantar antigen injection in sensitized rats increased paw volume and
      stimulated NGF biosynthesis in the skin of the injected paw as determined 3 and 6
      h after injection. Treatment of rats with terbutaline (0.1 - 0.3 mg kg(-1), s.c.)
      had no significant effect on the NGF concentration in non-inflamed skin, but
      reduced oedema, and at 0.3 mg kg(-1) also NGF mRNA and immunoreactive NGF in the
      skin of the inflamed paw in a propranolol-reversible manner. In carrageenan
      induced inflammation, terbutaline did not significantly reduce the inflammation
      induced increase of NGF in paw skin. 3. Exposure of sensitized rats to
      aerosolized antigen (twice, 24 h interval) increased protein content, eosinophil
      leukocytes, and immunoreactive NGF in the bronchoalveolar lavage fluid (BAL,
      obtained 16 h after the second antigen exposure). Treatment of rats with
      terbutaline (0.3 mg kg(-1), s.c. 30 min before the second antigen challenge)
      suppressed antigen-induced elevation of protein and eosinophil leukocytes, and
      reduced the concentration of NGF in BAL to values similar to those found in non
      sensitized rats. 4. The present results demonstrate anti-allergic properties of
      terbutaline in rats that were accompanied by a marked reduction of antigen
      induced NGF increase in skin and BAL, respectively. These results are compatible
      with the assumption that terbutaline primarily suppressed the immune response to
      antigen thereby attenuating the release of vasoactive mediators and the
      stimulation of NGF biosynthesis.

PMID- 11325810
TI  - Glimepiride block of cloned beta-cell, cardiac and smooth muscle K(ATP) channels.
AB  - 1. We examined the effect of the sulphonylurea glimepiride on three types of
      recombinant ATP-sensitive potassium (K(ATP)) channels. 2. K(ATP) channels share a
      common pore-forming subunit, Kir6.2, which associates with different
      sulphonylurea receptor isoforms (SUR1 in beta-cells, SUR2A in heart and SUR2B in
      smooth muscle). 3. Kir6.2 was coexpressed with SUR1, SUR2A or SUR2B in Xenopus
      oocytes and macroscopic K(ATP) currents were recorded from giant inside-out
      membrane patches. Glimepiride was added to the intracellular membrane surface. 4.
      Glimepiride inhibited Kir6.2/SUR currents by interaction with two sites: a low
      affinity site on Kir6.2 (IC(50)= approximately 400 microM) and a high-affinity
      site on SUR (IC(50)=3.0 nM for SUR1, 5.4 nM for SUR2A and 7.3 nM for SUR2B). The
      potency of glimepiride at the high-affinity site is close to that observed for
      glibenclamide (4 nM for SUR1, 27 nM for SUR2A), which has a similar structure. 5.
      Glimepiride inhibition of Kir6.2/SUR2A and Kir6.2/SUR2B currents, but not
      Kir6.2/SUR1 currents, reversed rapidly. 6. Our results indicate that glimepiride
      is a high-affinity sulphonylurea that does not select between the beta-cell,
      cardiac and smooth muscle types of recombinant K(ATP) channel, when measured in
      inside-out patches. High-affinity inhibition is mediated by interaction of the
      drug with the sulphonylurea receptor subunit of the channel.

PMID- 11325811
TI  - IL-17-induced cytokine release in human bronchial epithelial cells in vitro: role
      of mitogen-activated protein (MAP) kinases.
AB  - 1. Recent data indicate that interleukin (IL)-17 may contribute to neutrophilic
      airway inflammation by inducing the release of neutrophil-mobilizing cytokines
      from airway cells. The aim of this study was to evaluate the role of mitogen
      activated protein kinases in IL-17 induced release of IL-8 and IL-6 in bronchial
      epithelial cells. 2. Transformed human bronchial epithelial cells (16HBE) were
      stimulated with either IL-17 or vehicle. Both groups were treated either with
      SB202190 (inhibitor of p38 MAP kinase), PD98059 (inhibitor of extracellular
      signal-regulated kinase [ERK] pathway), Ro-31-7549 (protein kinase C [PKC]
      inhibitor), LY 294002 (a phosphatidylinositol 3-kinase [PI 3-kinase] inhibitor)
      or vehicle. IL-6 and IL-8 levels were measured in conditioned media by ELISA. 3.
      The IL-17-induced release of IL-6 and IL-8 was concentration-dependently
      inhibited by SB202190 and by PD98059 in bronchial epithelial cells without
      affecting cell proliferation or survival. 4. Ro-31-7549 and LY294002 had no
      significant effect on IL-17-induced IL-6 or IL-8 release in bronchial epithelial
      cells. 4. Taken together, these data indicate a role for p38 and ERK kinase
      pathways in IL-17-induced release of neutrophil-mobilizing cytokines in human
      bronchial epithelial cells. These mechanisms constitute potential
      pharmacotherapeutical targets for inhibition of the IL-17-mediated airway
      neutrophilia.

PMID- 11325812
TI  - Inhibition of m3 muscarinic acetylcholine receptors by local anaesthetics.
AB  - 1. Muscarinic m1 receptors are inhibited by local anaesthetics (LA) at nM
      concentrations. To elucidate in more detail the site(s) of LA interaction, we
      compared these findings with LA effects on m3 muscarinic receptors. 2. We
      expressed receptors in Xenopus oocytes. Using two-electrode voltage clamp, we
      measured the effects of lidocaine, QX314 (permanently charged) and benzocaine
      (permanently uncharged) on Ca(2+)-activated Cl(-)-currents (I(Cl(Ca))), elicited
      by acetyl-beta-methylcholine bromide (MCh). We also characterized the interaction
      of lidocaine with [(3)H]-quinuclydinyl benzylate ([(3)H]-QNB) binding to m3
      receptors. Antisense-injection was used to determine the role of specific G
      protein alpha subunits in mediating the inhibitory effects of LA. Using chimeric
      receptor constructs we investigated which domains of the muscarinic receptors
      contribute to the binding site for LA. 3. Lidocaine inhibited m3-signalling in a
      concentration-dependent, reversible, non-competitive manner with an IC(50) of 370
      nM, approximately 21 fold higher than the IC(50) (18 nM) reported for m1
      receptors. Intracellular inhibition of both signalling pathways by LA was
      similar, and dependent on the G(q)- protein alpha subunit. In contrast to results
      reported for the m1 receptor, the m3 receptor lacks the major extracellular
      binding site for charged LA. The N-terminus and third extracellular loop of the
      m1 muscarinic receptor molecule were identified as requirements to obtain
      extracellular inhibition by charged LA.

PMID- 11325813
TI  - Enhanced chemosensitivity to CPT-11 with proteasome inhibitor PS-341:
      implications for systemic nuclear factor-kappaB inhibition.
AB  - Inducible activation of nuclear factor-kappaB (NF-kappaB) inhibits the apoptotic
      response to chemotherapy and irradiation. Activation of NF-kappaB via
      phosphorylation of an inhibitor protein IkappaB leads to degradation of IkappaB
      through the ubiquitin-proteasome pathway. We hypothesized that inactivation of
      proteasome function will inhibit inducible NF-kappaB activation, thereby
      increasing levels of apoptosis in response to chemotherapy and enhancing
      antitumor effects. To assess the effects of proteasome inhibition on chemotherapy
      response, human colorectal cancer cells were pretreated with the dipeptide
      boronic acid analogue PS-341 (1 microM) prior to exposure to SN-38, the active
      metabolite of the topoisomerase I inhibitor, CPT-11. Inducible activation of NF
      kappaB and growth response were evaluated in vitro and in vivo. Effects on p53,
      p21, p27 and apoptosis were determined. Pretreatment with PS-341 inhibited
      activation of NF-kappaB induced by SN-38 and resulted in a significantly higher
      level of growth inhibition (64-75%) compared with treatment with PS-341 alone (20
      30%) or SN-38 alone (24-47%; P < 0.002). Combination therapy resulted in a 94%
      decrease in tumor size compared with the control group and significantly improved
      tumoricidal response to treatment compared with all treatment groups (P = 0.02).
      The level of apoptosis was 80-90% in the treatment group that received
      combination treatment compared with treatment with single agent alone (10%).
      Proteasome inhibition blocks chemotherapy-induced NF-kappaB activation, leading
      to a dramatic augmentation of chemosensitivity and enhanced apoptosis. Combining
      proteasome inhibition with chemotherapy has significant potential to overcome the
      high incidence of chemotherapy resistance. Clinical studies are currently in
      development to evaluate the role of proteasome inhibition as an important
      adjuvant to systemic chemotherapy.

PMID- 11325814
TI  - Mutations in fibroblast growth factor receptor 2 and fibroblast growth factor
      receptor 3 genes associated with human gastric and colorectal cancers.
AB  - Autosomal dominant disorders of skeletal and cranial development have been linked
      to fibroblast growth factor receptor (FGFR) 2 and FGFR3. Here we report two
      identical mutations in FGFR2 that cause craniosynostosis syndromes, Crouzon,
      Apert, and Pfeiffer in gastric carcinoma. A missense mutation (Ser267Pro) in exon
      IIIa and a splice site mutation (940-2A-->G) in exon IIIc were detected in
      gastric cancer patients. Interestingly, these heterozygous somatic mutations are
      identical to the germinal activating mutations in FGFR2 reported previously in
      craniosynostosis syndromes. In addition, the two novel mutations of FGFR3 in
      colorectal carcinomas were identified. All identified mutations occurred at
      highly conserved sequences, not only in the FGFR family of molecules, but also
      throughout evolution and clustered in the immunoglobulin-like loop-III domain,
      highlighting the functional importance of this domain. Our results indicate that
      FGFR2 and FGFR3, in addition to their potential role in skeletal dysplasias, play
      an important role in tumorigenesis.

PMID- 11325815
TI  - Alterations of gene expression during colorectal carcinogenesis revealed by cDNA
      microarrays after laser-capture microdissection of tumor tissues and normal
      epithelia.
AB  - To identify a set of genes involved in the development of colorectal
      carcinogenesis, we compared expression profiles of colorectal cancer cells from
      eight tumors with corresponding noncancerous colonic epithelia using a DNA
      microarray consisting of 9216 human genes. These cell populations had been
      rendered homogeneous by laser-capture microdissection. Expression change in more
      than half of the tumors was observed for 235 genes, i.e., 44 up-regulated and 191
      down-regulated genes. The differentially expressed genes include those associated
      with signal transduction, metabolizing enzymes, production of reactive oxygen
      species, cell cycle, transcription, mitosis, and apoptosis. Subsequent
      examination of 10 genes (five up-regulated and five down-regulated) by
      semiquantitative reverse transcription-PCR using the eight tumors together with
      an additional 12 samples substantiated the reliability of our analysis. The
      extensive list of genes identified in these experiments provides a large body of
      potentially valuable information of colorectal carcinogenesis and represents a
      source of novel targets for cancer therapy.

PMID- 11325816
TI  - Amplification and overexpression of androgen receptor gene in hormone-refractory
      prostate cancer.
AB  - The expression level of the androgen receptor (AR) gene in androgen-dependent and
      -independent prostate cancer was determined by using real-time quantitative
      reverse transcription-PCR assay. Eight benign prostate hyperplasias, 33 untreated
      and 13 hormone-refractory locally recurrent carcinomas, as well as 10 prostate
      cancer xenografts, were analyzed. All hormone-refractory tumors expressed AR and
      showed, on average, 6-fold higher expression than androgen-dependent tumors or
      benign prostate hyperplasias (P < 0.001). Four of 13 (31%) hormone-refractory
      tumors contained AR gene amplification detected by fluorescence in situ
      hybridization. Androgen-independent tumors with gene amplification expressed, on
      average, a 2-fold higher level of AR than the refractory tumors without the gene
      amplification. Two xenografts (LuCaP 35 and 69) showed amplification and high
      level expression of the AR gene. These xenografts are the first prostate cancer
      model systems containing the gene amplification. The findings demonstrate that AR
      is highly expressed in androgen-independent prostate cancer, suggesting that the
      AR signaling pathway is important in the progression of prostate cancer during
      endocrine treatment. The two xenografts with the AR gene amplification will
      enable studies evaluating the functional significance of the amplification and
      development of new treatment strategies based on high-level expression of AR.

PMID- 11325817
TI  - A genetically tractable model of human glioma formation.
AB  - Gliomas remain one of the deadliest forms of cancer. Improved therapeutics will
      require a better understanding of the molecular nature of these tumors. We,
      therefore, mimicked the most common genetic changes found in grade III-IV
      gliomas, disruption of the p53 and RB pathways and activation of telomere
      maintenance and independence from growth factors, through the ectopic expression
      of the SV40 T/t-Ag oncogene, an oncogenic form of H-ras (H-ras(V12G)), and the
      human telomerase catalytic subunit hTERT in normal human astrocytes. The
      resulting cells displayed many of the hallmarks of grade III-IV gliomas,
      including greatly expanded life span and growth in soft agar and, most
      importantly, were tumorigenic with pathology consistent with grade III-IV
      neuroectodermal tumors in mice. This model system will, for the first time, allow
      the biological significance of selected genetic alterations to be studied in
      human gliomas.

PMID- 11325818
TI  - Erythropoietin and erythropoietin receptor expression in human cancer.
AB  - Erythropoietin (EPO) stimulates the growth of erythroblasts in the bone marrow
      (C. Lacombe and P. Mayeux, NEPHROL: DIAL: TRANSPLANT:, 14 (SUPPL: 2): 22-28,
      1999). We report basal and hypoxia-stimulated expression of EPO and its receptor,
      EPOR, in human breast cancer cells, and we demonstrate EPO-stimulated tyrosine
      phosphorylation and the proliferation of these cells in vitro. In 50 clinical
      specimens of breast carcinoma, we report high levels of EPO and EPOR associated
      with malignant cells and tumor vasculature but not with normal breast, benign
      papilloma, or fibrocystic tissue. Hypoxic tumor regions display the highest
      levels of EPO and EPOR expression. Enhanced EPO signaling may contribute to the
      promotion of human cancer by tissue hypoxia.

PMID- 11325819
TI  - CYP2C9 and UGT1A6 genotypes modulate the protective effect of aspirin on colon
      adenoma risk.
AB  - Regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) has a protective
      effect on the incidence of colon neoplasia. However, polymorphisms in NSAID
      metabolizing enzymes may alter this effect. NSAIDs, particularly aspirin, are
      glucuronidated by UGT1A6 and some classes of NSAIDs are also metabolized by
      cytochrome P450 (CYP) 2C9. Both of these enzymes have slow-metabolizing, variant
      forms. We tested the hypothesis that the slow alleles of these enzymes can modify
      the inverse association between NSAIDs and colon neoplasia in the Minnesota
      Cancer Prevention Research Unit (CPRU) adenomatous polyp case-control study.
      CYP2C9 and UGT1A6 genotypes were determined for 474 adenoma cases and 563
      controls. NSAID use was inversely associated with adenoma risk [odds ratio (OR),
      0.63; 95% confidence interval (CI), 0.44-0.90 for aspirin; and OR, 0.50; 95% CI,
      0.31-0.82 for nonaspirin NSAID]. However, this association was absent in aspirin
      users who carried the CYP2C9 variant alleles (OR, 0.88; 95% CI, 0.51-1.53) or who
      were homozygous wild-type UGT1A6 (OR, 0.86; 95% CI, 0.50-1.50). Carriers of both
      of these alleles who use aspirin were also not at reduced risk of adenomatous
      polyps (OR, 1.59; 95% CI, 0.68-3.73). The variants of these enzymes did not
      influence the association between nonaspirin NSAIDs and adenoma risk. These data
      indicate that the effectiveness of chemopreventive drugs can be modulated by the
      genotype of metabolizing enzymes.

PMID- 11325820
TI  - Mutations in the Nijmegen Breakage Syndrome gene (NBS1) in childhood acute
      lymphoblastic leukemia (ALL).
AB  - The Nijmegen Breakage Syndrome (NBS) is a rare autosomal recessive disorder
      associated with immune deficiency, chromosome fragility, and increased
      susceptibility to lymphoid malignancies. The aim of the present study was to
      elucidate the potential role of the gene mutated in NBS (NBS1) in the
      pathogenesis and disease progression of childhood acute lymphoblastic leukemia
      (ALL). Samples from 47 children with first relapse of ALL were analyzed for
      mutations in all 16 exons of the NBS1 gene, and in 7 of them (14.9%), four novel
      amino acid substitutions were identified. Mutations S93L, D95N, and I171V occur
      in the two known domains of nibrin that are probably involved in protein-protein
      interactions. Germ-line origin of the I171V mutation was confirmed in three
      patients, whereas the D95N exchange was present only in leukemic cells. The R215W
      mutation was observed in one ALL but also in a population-based study and
      probably represents a rare sequence variant. No additional mutations were found
      on the second allele in any of these seven patients. The observed NBS1 gene
      mutations in ALL patients points to its possible involvement in the pathogenesis
      of this disease.

PMID- 11325821
TI  - Accelerated age-related CpG island methylation in ulcerative colitis.
AB  - CpG island hypermethylation is a mechanism of gene silencing that can be usurped
      by neoplastic cells to inactivate undesirable genes. In the colon,
      hypermethylation often starts in normal mucosa as a function of age and is
      markedly increased in cancer. To test the hypothesis that subjects at increased
      risk of colon cancer have higher levels of methylation in their nonneoplastic
      mucosa, we studied methylation patterns of five genes in the normal and
      dysplastic mucosa of patients with ulcerative colitis (UC), a condition
      associated with a marked increased risk of colon cancer. One gene (Mlh1) was
      unmethylated in all tissues examined. All four remaining genes had low but
      detectable levels of methylation in the epithelium of UC patients without
      evidence of dysplasia, and this methylation was not different from non-UC
      controls. By contrast, all four genes were highly methylated in dysplastic
      epithelium from high-grade dysplasia (HGD)/cancer patients with UC; methylation
      in HGD versus controls averaged 40.0% versus 7.4% (P = 0.00003) for ER, 44.0%
      versus 3.0% (P < 0.00003) for MYOD, 9.4% versus 2.4% (P = 0.03) for p16 exon 1,
      and 57.5% versus 30.6% (P = 0.01) for CSPG2. Importantly, three of the four genes
      were also highly methylated in the normal appearing (nondysplastic) epithelium
      from these same HGD/cancer patients, indicating that methylation precedes
      dysplasia and is widespread in these patients. Compared with controls,
      methylation averaged 20.1% versus 7.2% (P = 0.07) for ER, 18.4% versus 3.0% (P <
      0.008) for MYOD, and 7.9% versus 2.4% (P = 0.007) for p16 exon 1. These results
      are consistent with the hypothesis that age-related methylation marks (and may
      lead to) the field defect that reflects acquired predisposition to colorectal
      neoplasia. Furthermore, the data suggest that chronic inflammation is associated
      with high levels of methylation, perhaps as a result of increased cell turnover,
      and that UC can be viewed as resulting in premature aging of colorectal
      epithelial cells.

PMID- 11325822
TI  - Loss of heterozygosity events impeding breast cancer metastasis contain the MTA1
      gene.
AB  - Breast cancer mortality is seldom attributable to the primary tumor, but rather
      to the presence of systemic (metastatic) disease. Axillary lymph node dissection
      can identify the presence of metastatic breast cancer cells and serves as a
      marker for systemic disease. Previous work in our laboratory determined that
      rates of loss of heterozygosity (LOH) of a 1.6-Mb region of chromosome 14q 31.2
      is much higher in axillary lymph node-negative primary breast tumors than in
      axillary lymph node-positive primary breast tumors (P. O'Connell et al., J. NATL:
      Cancer INST:, 91: 1391-1397, 1999.). This unusual observation suggests that,
      whereas the LOH of this region promotes primary breast cancer formation, some
      gene(s) mapping to this 1.6-Mb region is rate-limiting for breast cancer
      metastasis. Thus, if primary breast cancers delete this region, their ability to
      metastasize decreases. To identify this gene(s), we have physically mapped this
      area of chromosome 14q, confirmed the position of two known genes and 13 other
      expressed sequence tags into this 1.6-Mb region. One of these, the metastasis
      associated 1 (MTA1) gene, previously identified as a metastasis-promoting gene
      (Y. Toh et al., J. BIOL: CHEM:, 269: 22958-22963, 1994.), mapped to the center of
      our 1.6-Mb target region. Thus, MTA1 represents a strong candidate for this
      breast cancer metastasis-promoting gene.

PMID- 11325823
TI  - 5' CpG island methylation of the FHIT gene is correlated with loss of gene
      expression in lung and breast cancer.
AB  - Allele loss and loss of expression of fragile histidine triad (FHIT), a putative
      tumor suppressor gene located in chromosome region 3p14.2, are frequent in
      several types of cancers. Tumor-acquired methylation of promoter region CpG
      islands is one method for silencing tumor suppressor genes. We investigated 5'
      CpG island methylation of the FHIT gene in 107 primary non-small cell lung cancer
      (NSCLC) samples and corresponding nonmalignant lung tissues, 39 primary breast
      carcinomas, as well as in 49 lung and 22 breast cancer cell lines by a
      methylation-specific PCR assay. In addition, we analyzed brushes from the
      bronchial epithelium of 35 heavy smokers without cancer. FHIT methylation was
      detected in 37% of primary NSCLCs, 31% of primary breast cancers, and 65% of lung
      and 86% of breast cancer cell lines. The frequency of methylation in small cell
      and NSCLC cell lines were identical. Methylation was found in 9% of the
      corresponding nonmalignant lung tissues and in 17% of bronchial brushes from
      heavy cigarette smokers. FHIT methylation was significantly correlated with loss
      of FHIT mRNA expression by Northern blot analysis in lung cancer cell lines and
      with loss of Fhit expression in NSCLC and breast tumors by immunostaining. We
      conclude that methylation of FHIT is a frequent event in NSCLC and breast cancers
      and is an important mechanism for loss of expression of this gene. Methylation of
      FHIT commences during lung cancer pathogenesis and may represent a marker for
      risk assessment.

PMID- 11325824
TI  - Oncogenic TLS/ERG and EWS/Fli-1 fusion proteins inhibit RNA splicing mediated by
      YB-1 protein.
AB  - The translocation liposarcoma protein TLS has recently been shown to function as
      an adapter molecule coupling gene transcription to RNA splicing. Here we
      demonstrate that YB-1, a protein known to play important roles in transcription
      and translation, interacts with the COOH-terminal domains of TLS and the
      structurally related Ewing's sarcoma protein EWS. Through this interaction, YB-1
      is recruited to RNA polymerase II and promotes splicing of E1A pre-mRNA to the
      13S isoform. This splicing function of YB-1 is inhibited by exogenous TLS/ERG or
      EWS/Fli-1 fusion proteins, which bind to RNA polymerase II but fail to recruit
      the YB-1 protein. In Ewing's sarcoma cells that express endogenous EWS/Fli-1,
      this linkage between YB-1 and RNA Pol II via EWS (or TLS) was found to be
      defective. Together, these results suggest that TLS and EWS fusion proteins may
      contribute to malignant transformation through disruption of RNA splicing
      mediated by TLS- and EWS-binding proteins such as YB-1.

PMID- 11325825
TI  - The histone deacetylase inhibitor, CBHA, inhibits growth of human neuroblastoma
      xenografts in vivo, alone and synergistically with all-trans retinoic acid.
AB  - Histone deacetylase inhibitors (HDACIs) inhibit the growth of a variety of
      transformed cells in culture. We demonstrated previously that the hybrid-polar
      HDACI m-carboxycinnamic acid bis-hydroxamide (CBHA) induces apoptosis of human
      neuroblastoma in vitro and is effective in lower doses when combined with
      retinoids. The current study investigates the effect of CBHA on the growth of
      human neuroblastoma in vivo, both alone and in combination with all-trans
      retinoic acid (atRA), using a severe combined immunodeficiency-mouse xenograft
      model. CBHA (50, 100, and 200 mg/kg/day) inhibited growth of SMS-KCN-69n tumor
      xenografts in a dose-dependent fashion, with 200 mg/kg CBHA resulting in a
      complete suppression of tumor growth. The efficacy of 50 and 100 mg/kg CBHA was
      enhanced by the addition of 2.5 mg/kg atRA. This dose of atRA was ineffective
      when administered alone. Treatment was accompanied by mild weight loss in all
      groups except the lowest dose of CBHA. Our results suggest HDACIs alone or
      combined with retinoids may have therapeutic utility for neuroblastoma.

PMID- 11325826
TI  - Active Ras induces heterodimerization of cRaf and BRaf.
AB  - Growth factor-induced signalling leads to activation of members of the Ras family
      and subsequent stimulation of different Raf isoforms. Within the mechanism of Raf
      activation, two isoforms of Raf, cRaf and BRaf, may cooperate. We investigated
      the relationship between cRaf and BRaf and found that active Ras induced
      heterodimerization of cRaf and BRaf, an effect that was dependent on the serine
      residue at position 621 of cRAF: Moreover, we also found that cRaf COOH-terminus
      constitutively associated with BRaf, whereas the NH(2) terminus did not, even in
      the presence of active RAS: These data suggest that Ras induces the cRaf-BRaf
      complex formation through the exposure of 14-3-3 binding sites in the COOH
      terminus of cRAF: Thus, Ras-induced cRaf-Braf heterodimerization may explain the
      observed cooperativity of cRaf and BRaf in cells responding to growth factor
      signals.

PMID- 11325827
TI  - Detection of increased choline compounds with proton nuclear magnetic resonance
      spectroscopy subsequent to malignant transformation of human prostatic epithelial
      cells.
AB  - In this study, a panel of normal human prostate cells (HPCs) and tumor cells
      derived from metastases were studied by (1)H NMR spectroscopy to determine
      whether the malignant transformation of HPCs results in the elevation of choline
      compounds. Although an elevated choline signal has been observed previously in
      clinical studies, the contribution of the different Cho compounds to this
      elevation, as well as their quantification, has not been established until now.
      Here we have shown that HPCs derived from metastases exhibit significantly higher
      phosphocholine as well as glycerophosphocholine levels compared with normal
      prostate epithelial and stromal cells. Thus the elevation of the choline peak
      observed clinically in prostate cancer is attributable to an alteration of
      phospholipid metabolism and not simply to increased cell density, doubling time,
      or other nonspecific effects. Androgen deprivation of the androgen receptor
      positive cell lines resulted in a significant increase of choline compounds after
      chronic androgen deprivation of the LNCaP cell line and in a decrease of choline
      compounds after a more acute androgen deprivation of the LAPC-4 cell line. These
      data strongly support the use of proton magnetic resonance spectroscopic imaging
      to detect the presence of prostate cancer for diagnosis, to detect response
      subsequent to androgen ablation therapy, and to detect recurrence.

PMID- 11325828
TI  - Mechanism of attenuation of skeletal muscle protein catabolism in cancer cachexia
      by eicosapentaenoic acid.
AB  - Cancer cachexia is characterized by selective depletion of skeletal muscle
      protein reserves. Soleus muscles from mice bearing a cachexia-inducing tumor
      (MAC16) showed an increased protein degradation in vitro, as measured by tyrosine
      release, when compared with muscles from nontumor-bearing animals. After
      incubation under conditions that modify different proteolytic systems, lysosomal,
      calcium-dependent, and ATP-dependent proteolysis were found to contribute to the
      elevated protein catabolism. Treatment of mice bearing the MAC16 tumor with the
      polyunsaturated fatty acid, eicosapentaenoic acid (EPA), attenuated loss of body
      weight and significantly suppressed protein catabolism in soleus muscles through
      an inhibition of an ATP-dependent proteolytic pathway. The ATP-ubiquitin
      dependent proteolytic pathway is considered to play a major role in muscle
      catabolism in cachexia, and functional proteasome activity, as determined by
      "chymotrypsin-like" enzyme activity, was significantly elevated in gastrocnemius
      muscle of mice bearing the MAC16 tumor as weight loss progressed. When animals
      bearing the MAC16 tumor were treated with EPA, functional proteasome activity was
      completely suppressed, together with attenuation of the expression of 20S
      proteasome alpha-subunits and the p42 regulator, whereas there was no effect on
      the expression of the ubiquitin-conjugating enzyme (E2(14k)). These results
      suggest that EPA induces an attenuation of the up-regulation of proteasome
      expression in cachectic mice, and this was correlated with an increase in myosin
      expression, confirming retention of contractile proteins. EPA also inhibited
      growth of the MAC16 tumor in a dose-dependent manner, and this correlated with
      suppression of the expression of the 20S proteasome alpha-subunits in tumor
      cells, suggesting that this may be the mechanism of tumor growth inhibition. Thus
      EPA antagonizes loss of skeletal muscle proteins in cancer cachexia by down
      regulation of proteasome expression, and this may also be the mechanism for
      inhibition of tumor growth.

PMID- 11325829
TI  - Tissue inhibitor of metalloproteinases-4 inhibits but does not support the
      activation of gelatinase A via efficient inhibition of membrane type 1-matrix
      metalloproteinase.
AB  - The tissue inhibitors of metalloproteinases 1-4 (TIMPs) have discrete regulatory
      roles in the activation of matrix metalloproteinase (MMP)-2 (gelatinase A), an
      important basement membrane-degrading MMP pivotal to tumor metastasis and
      angiogenesis. TIMP-2 binds to both the hemopexin C domain of progelatinase A and
      the active site of membrane type-1 (MT1) MMP. This trimeric complex presents the
      cell surface-bound gelatinase A zymogen to a free MT1-MMP molecule for
      activation. To investigate the role of TIMP-4 in the activation process, we
      developed a new procedure for the expression and purification of recombinant
      human TIMP-4 from baby hamster kidney cells. The recombinant TIMP-4 was a potent
      inhibitor of gelatinase A (apparent K(i) [Ki(app.)] < or = 9 pM; k(on)
      (association rate constant), 4.57 +/- 0.13 x 10(6) M(-1)s(-1)) and was less
      dependent upon hemopexin C domain interactions than TIMP-2 in its mode of binding
      and inhibition. Unlike TIMP-1, TIMP-4 strongly inhibited MT1-MMP (Ki(app.) < or =
      100 pM; k(on), 3.49 +/- 0.34 x 10(6) M(-1)s(-1)) and blocked the concanavalin A
      induced cellular activation of progelatinase A. In concanavalin A-stimulated
      homozygous Timp2 -/- fibroblasts or unstimulated MT1-MMP-transfected Timp2 -/-
      cells, which cannot activate progelatinase A, activation was restored by the
      addition of 0.3-5 nM TIMP-2 but not by TIMP-4, unequivocally showing the TIMP-2
      dependency of MT1-MMP-induced activation of gelatinase A and the fact that TIMP-4
      cannot support activation. The dominance of TIMP-2 in the activation process was
      further supported by the preferential binding of TIMP-2 compared with TIMP-4 to
      the hemopexin C domain of progelatinase A in inhibitor mixtures and by the
      ability of TIMP-2 to displace TIMP-4 from the hemopexin C domain. Hence, TIMP-4
      regulates gelatinase A activity by efficient inhibition of MT1-MMP-mediated
      activation and by inhibiting the activated enzyme and, thus, is a tumor
      resistance factor in the peritumor stroma.

PMID- 11325830
TI  - Targeted expression of bcl-2 to murine basal epidermal keratinocytes results in
      paradoxical retardation of ultraviolet- and chemical-induced tumorigenesis.
AB  - The antiapoptotic protein bcl-2 is found up-regulated in a number of malignant
      and premalignant skin conditions of keratinocyte origin, but in normal skin, it
      is expressed at low levels only in interfollicular epidermis. To investigate
      whether unregulated bcl-2 expression could affect the incidence of epidermal
      tumors, we have generated a mouse line that over-expresses human bcl-2 in the
      basal layer of epidermis under the control of the human keratin 14 promoter.
      These mice were subjected to both UVB photocarcinogenesis and classical two-stage
      chemical carcinogenesis. Although transgenic bcl-2 in these mice reduces the
      formation of sunburn cells after short-term UVB irradiation, chronically UVB
      irradiated K14/bcl-2 mice were protected against tumor development, because
      transgenic mice developed tumors much later and at a significantly lower
      frequency than controls. Immunohistochemical analyses of the UVB-induced tumors
      revealed no significant differences in the degree of inflammatory cell
      infiltrates. When either K14/bcl-2 mice or F(1) progeny of matings with mice
      expressing an activated Ha-ras oncogene (K14/bcl-2/ras) were treated with 9,10
      dimethyl-1,2-benzanthracene/phorbol 12-myristate 13-acetate, the latency of first
      papilloma appearance was the same in transgenic mice and controls, but further
      papillomas developed more slowly in the mutant mice. Moreover, the K14/bcl-2/ras
      mice developed far fewer albeit larger tumors/mouse than did the ras/+ controls.
      The rate of conversion to malignant carcinomas, the carcinoma grade, and the
      frequency of lymph node metastases were not significantly different between
      mutants and controls. We conclude that, despite its antiapoptotic function, bcl
      2, overexpressed in basal epidermal keratinocytes, exerts a paradoxical
      retardation on the development of skin tumors induced by chemical carcinogens and
      particularly by UVB.

PMID- 11325831
TI  - Evidence of DNA repair/processing defects in cultured skin fibroblasts from
      breast cancer patients.
AB  - Cultured skin fibroblasts from 14 breast cancer (BC) patients were compared with
      those from 8 healthy subjects and 4 ataxia-telangiectasia (A-T) cases for
      sensitivity to low dose-rate (0.007 Gy/min) gamma-irradiation assessed by a
      colony-forming assay and for postirradiation DNA synthesis inhibition determined
      by the method of [(3)H]thymidine incorporation. Fibroblasts from all but two BC
      patients exhibited moderately enhanced radiosensitivity in the colony-forming
      assay, occupying an intermediate position between the controls and the A-T cases.
      Fibroblasts from the radiosensitive BC patients also showed an intermediate
      response with respect to radio-induced DNA synthesis inhibition compared with
      those from controls and A-T cases. In a host cell reactivation assay using an
      irradiated herpes simplex virus for plaque-forming ability, the fibroblasts from
      7 BC patients, used as host cells, resulted in a significantly reduced (P <
      0.0001) recovery of the virus relative to the 8 control fibroblasts, suggesting a
      deficiency in DNA repair in the former. A number of the BC fibroblasts analyzed
      in an assay for potentially lethal damage repair confirmed the repair deficiency
      in the fibroblasts from the BC patients. Defects in DNA repair and/or DNA
      processing after exposure to genotoxic agents would lead to genomic instability
      and hence would be responsible for cancer predisposition. Our data suggest that
      most BC patients may carry various genes resulting in such defects, and
      additional studies on normal cells from a larger cohort of BC patients and their
      family members are warranted to establish a connection between mutations or
      polymorphisms in specific DNA repair genes and susceptibility to breast cancer.

PMID- 11325832
TI  - Silencing and reactivation of the selective estrogen receptor modulator-estrogen
      receptor alpha complex.
AB  - 4-Hydroxytamoxifen (4-OHT), a selective estrogen receptor modulator, is an
      agonist at a transforming growth factor-alpha (TGF-alpha) target gene in situ in
      MDA-MB-231 human breast cancer cells stably transfected with wild-type human
      ERalpha. In contrast, raloxifene (Ral) is a complete antiestrogen silencing
      activation function (AF) 1 and AF2 in this system. A natural mutation
      D351YERalpha enhances 4-OHT agonist activity and changes Ral-like compounds from
      antagonists to partial agonists. We reasoned that: either the conformation of the
      Ral-D351YERalpha is altered, thereby reactivating AF2 in the ligand binding
      domain, or the change at amino acid 351 allosterically reactivates AF1 in the Ral
      D351YERalpha complex. Unlike the estradiol-ERalpha complex, agonist activity of 4
      OHT and raloxifene through ERalpha and D351YERalpha were not attributed to
      coactivator (such as SRC-1, AIB1) binding to the ligand binding domain. We
      conclude that the classic AF2 is not responsible for the agonist activities of 4
      OHT-ERalpha, 4-OHT-D351YERalpha, and Ral-D351YERalpha. To address the role of
      AF1, stable transfectants of ERalpha or D351YERalpha with an AF1 deletion
      (D351deltaAF1, D351YdeltaAF1) were generated in MDA-MB-231 cells. Additionally,
      D538A/E542A/D545A triple mutations within helix 12 (D351-3m, D351Y3m) or the COOH
      terminal 537 deletion (D351delta537) were tested. The agonist activities of 4-OHT
      and raloxifene were lost in these stable transfectants, but antiestrogenic action
      was retained. The reactivation of an estrogen-like property of the Ral-ERalpha
      complex through AF1 with the D351Y mutation illustrates a novel allosteric
      mechanism for the selective estrogen receptor modulator ERalpha complex.

PMID- 11325833
TI  - Transcriptional activation of the thyroglobulin promoter directing suicide gene
      expression by thyroid transcription factor-1 in thyroid cancer cells.
AB  - Gene therapy with thyroglobulin (TG) promoter and a prodrug/suicide gene
      combination may prove useful as a treatment for thyroid carcinoma. However, most
      poorly differentiated and anaplastic thyroid carcinomas have lost the ability to
      express the TG gene expression accompanied by loss of transcription factors
      [thyroid transcription factor-1 (TTF-1), TTF-2, or Pax-8] interacting with the TG
      promoter. In anticipation of developing transcriptionally targeted gene therapy
      of TG-nonproducing thyroid carcinomas, we investigated the effect of TTF-1 gene
      transfer on TG promoter activity and the cytotoxic effect obtained by the TG
      promoter-driven HSV-TK gene along with ganciclovir in thyroid carcinoma and
      nonthyroidal cells. Using a chimeric construct containing the 5'-flanking region
      of the rat TG gene between -826 and +39 bp and the luciferase gene, TG promoter
      activity was detected in a normal rat thyroid cell line (FRTL-5), but not in a
      dedifferentiated line of thyroid cells (FRT) expressing Pax-8 but not TTF-1, TTF
      2, or TG [TTF-1(-)/TTF-2(-)/Pax-8(+)/TG(-)], or in a human papillary thyroid
      carcinoma cell line [BHP15-3; TTF-1(-)/TTF-2(-)/Pax-8(-)/TG(-)], a human
      pulmonary cell line [H441; TTF-1(+)/TTF-2(-)/Pax-8(-)/TG(-)], or a dog kidney
      epithelial cell line [MDCK; TTF-1(-)/TTF-2(-)/Pax-8(+)/TG(-)]. Cotransfection of
      the TTF-1 expression vector stimulated TG promoter activity in FRT and BHP15-3
      dedifferentiated thyroid cells, but not in H441 pulmonary cells. Only weak
      activation was observed in MDCK kidney cells. We then constructed recombinant
      adenovirus vectors, AdTTF-1 and ADTGTK: AdTTF-1 contained cytomegalovirus
      promoter and rat TTF-1 cDNA; AdTGTK carried the TG promoter-driven HSV-TK gene.
      Infection with AdTGTK and combined with GCV treatment induced a cytotoxic effect
      in FRTL-5 cells but not in dedifferentiated thyroid or nonthyroid cells.
      Cotransduction of AdTTF-1 and AdTGTK permitted 90% cytotoxicity for BHP15-3 and
      >95% cytotoxicity for FRT, as well as for BHP7-13 and BHP18-21v thyroid cancer
      cell lines [both/TTF1(-)/TTF-2(-)/Pax-8(+)/TG(-)]. In contrast, little
      cytotoxicity was seen for H441 and MDCK cell lines even with 300 microg/ml of
      ganciclovir. These results suggest that cotransduction of a TG promoter
      controlled suicide gene and the TTF-1 gene by adenoviral vectors confers
      transcriptionally targeted gene-mediated cytotoxicity in poorly differentiated
      thyroid carcinoma cells unable to express the TG gene.

PMID- 11325834
TI  - Chemoprevention of colon cancer by a glutathione conjugate of 1,4
      phenylenebis(methylene)selenocyanate, a novel organoselenium compound with low
      toxicity.
AB  - We have consistently shown that several synthetic Organoselenium compounds are
      superior cancer chemopreventive agents and less toxic than selenite or certain
      naturally occurring selenoamino acids. 1,4-Phenylenebis(methylene)selenocyanate
      (p-XSC) is the lead Organoselenium compound in that it has been shown to be the
      most effective and the least toxic agent in several experimental cancer models.
      It is not known whether p-XSC or one of its metabolites is responsible for its
      chemopreventive efficacy. As an initial step, we synthesized one of its putative
      metabolites, i.e., the glutathione conjugate of p-XSC (p-XSe-SG), and determined
      its stability in the pH range from 2 to 8 and in the diet under normal feeding
      conditions. We also assessed its maximum tolerated dose and examined its
      chemopreventive efficacy against azoxymethane (AOM)-induced colon carcinogenesis
      in male F344 rats. p-XSe-SG proved to be very stable over the pH range tested.
      The maximum tolerated dose of p-XSe-SG determined in a 6-week subchronic toxicity
      study was found to be >210 ppm (>40 ppm selenium) when the compound was added to
      AIN-76A high-fat diet. To assess the efficacy of this agent in the postinitiation
      period of colon carcinogenesis, male F344 rats 6 weeks of age were fed the high
      fat diet, and at beginning of weeks 7 and 8, all of the rats intended for
      carcinogen treatment were given AOM at a dose of 15 mg/kg body weight by s.c.
      injection. Two days after the carcinogen treatment, the groups of rats consuming
      the high-fat control diet began their respective high-fat experimental diet
      regimens with 0, 56, or 84 ppm p-XSe-SG (0.1, 10, and 15 ppm of selenium)
      supplementation. All animals continued on their respective diets for 38 weeks
      after the AOM-treatment and were then killed. Colon tumors were evaluated
      histologically using routine procedures and were also analyzed for cyclooxygenase
      (COX)-1 and COX-2 expression and enzymatic activities. The results indicate that
      p-XSeSG administered during the post-initiation stage significantly inhibited
      both the incidence (P < 0.05-0.01) and the multiplicity (P < 0.05-0.005) of AOM
      induced colon adenocarcinomas. This agent also greatly suppressed the
      multiplicity (P < 0.01-0.001) of AOM-induced exophytic adenocarcinomas in a dose
      dependent manner. Feeding of 56 or 84 ppm p-XSe-SG in the diet significantly
      suppressed total COX activity (P < 0.02 to -0.01) and COX-2 specific activity (P
      < 0.005-0.0005) but had minimal effect on the protein expression levels of COX-1
      and COX-2. These results suggest that the newly developed synthetic
      Organoselenium compound, p-XSe-SG, is stable in the diet and at wide pH ranges,
      inhibits colon carcinogenesis when administered during the postinitiation stage,
      and inhibits COX activity. Compared with previous efficacy studies and
      considering the toxicity associated with selenium, p-XSe-SG seems to be the least
      toxic Organoselenium chemopreventive agent thus far tested in the experimental
      colon carcinogenesis. Studies are in progress to delineate whether p-XSe-SG is
      also effective when administered during the progression stage of colon
      carcinogenesis.

PMID- 11325835
TI  - A strategy for antitumor vascular therapy by targeting the vascular endothelial
      growth factor: receptor complex.
AB  - Vascular endothelial growth factor (VEGF) is produced by cancer cells in response
      to hypoxia and is the primary stimulant of vascularization in solid tumors.
      Endothelial cells lining the blood vessels of these tumors have a high
      concentration of receptor-bound VEGF on their surface, providing a target for
      antibody- directed cancer therapy. To obtain a cloned antibody to this target
      when bound to its receptor on tumor endothelium, we used phage display technology
      to create a single-chain Fv (sFv) antibody library from mice immunized with the
      165-amino acid isoform of human VEGF-A. We selected, purified, and characterized
      LL4, an anti-VEGF sFv that was shown to react with receptor-bound VEGF. LL4 bound
      selectively to blood vessel endothelium, as shown by immunohistochemistry on
      tissue sections of human tumors. Furthermore, using autoradiography and grain
      counting of histological sections, systemically administered LL4 was shown to
      localize selectively to the endothelial lining of tumor blood vessels in human
      colorectal carcinoma xenografts in vivo. This study demonstrates the feasibility
      of targeting tumor vasculature using recombinant antibodies to the VEGF:receptor
      complex.

PMID- 11325836
TI  - Indolinone tyrosine kinase inhibitors block Kit activation and growth of small
      cell lung cancer cells.
AB  - Six indolinone tyrosine kinase inhibitors were characterized for their ability to
      inhibit Kit kinase and for their effects on the growth of small cell lung cancer
      (SCLC) cell lines. All of the six compounds were potent inhibitors of Kit kinase
      in a biochemical assay. A homology model of compound binding to the ATP binding
      site could account for the increased potency observed with the addition of a
      propionate moiety to the indolinone core but not the increase observed with
      addition of a chloride moiety. Although all of the compounds tested were potent
      in the biochemical assay, several exhibited significantly less potency in
      cellular kinase assays. Their effects on stem cell factor (SCF)-dependent Kit
      autophosphorylation and SCLC cell growth were also examined. Inhibition of SCF
      stimulated Kit activation and cell growth in the H526 cell line was dose
      dependent. At concentrations that inhibited SCF-stimulated H526 cell growth,
      there was little effect on insulin-like growth factor-1-stimulated growth,
      suggesting that these compounds exhibit reasonable selectivity for inhibition of
      Kit-mediated proliferation. Higher doses of the compounds were needed to inhibit
      serum-stimulated growth. Of the six compounds examined, SU5416 and SU6597
      demonstrated the best cellular potency and, therefore, their effect on the growth
      of multiple SCLC cell lines in serum-containing media was examined. In addition
      to inhibiting proliferation, these compounds also induced significant cell death
      of several SCLC cell lines, but not of normal human diploid fibroblasts, in
      complete media. These observations suggest that Kit kinase inhibitors such as
      these may offer a new approach for inhibiting Kit-mediated proliferation of
      tumors such as SCLC, gastrointestinal stromal tumors, seminomas, and leukemias.

PMID- 11325837
TI  - Lipid association improves the therapeutic index of lomustine [1-(2-chloroethyl)
      3-cyclohexyl-1-nitrosourea] to suppress 36B-10 tumor growth in rats.
AB  - The therapeutic efficacy and tumor accumulation of a liposome formulation of 1-(2
      chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), an effective agent used in the
      treatment of malignant brain tumors, was examined in an animal tumor model.
      Pharmacokinetic studies in normal and tumor-bearing rats indicated that a 2-fold
      greater plasma exposure was achieved with liposome-formulated CCNU compared with
      the free drug. In Fisher rats bearing s.c. tumors 36B-10, tumor growth was
      delayed substantially when liposomal CCNU was delivered compared with free-drug
      treatment. In single-dose treatments of 20, 35, and 50 mg/kg, tumor progression
      after each dose was reduced approximately 2-fold with liposomal compared with
      free CCNU (four animals in each treatment group). Multiple-dose treatments (given
      as three weekly doses with eight animals in each treatment group) with cumulative
      doses of 80 and 100 mg/kg of free and liposomal CCNU also resulted in a 2-fold
      reduction in tumor progression when compared with free-drug treatment. When drug
      levels in tumors relative to plasma were examined, it was observed that tumor
      drug concentrations did not exceed those found in plasma after administration of
      free CCNU; after administration of liposomal CCNU, however, tumor concentrations
      exceeded those in plasma by nearly 10-fold. These results suggest that the
      increased efficacy of liposome-formulated CCNU may be attributable to enhanced
      drug accumulation in tumor tissues.

PMID- 11325838
TI  - Modulation of both endogenous folates and thymidine enhance the therapeutic
      efficacy of thymidylate synthase inhibitors.
AB  - Plasma levels of folates and thymidine in mice are about 10-fold higher than in
      humans and may influence the therapeutic efficacy of thymidylate synthase (TS)
      inhibitors, such as 5-fluorouracil (5FU) and the antifolates pemetrexed (MTA) and
      raltitrexed (RTX). Therefore, we tested their therapeutic efficacy in various
      murine tumor models, grown in mice on a normal and a folate-depleted diet, with
      high and low thymidine kinase (TK) levels. MTA and RTX were inactive against
      Colon-26-10 [doubling times gained by treatment; growth delay factor (GDF), 0.5
      and 0.3, respectively], whereas 5FU was very active (GDF, >10; complete cures).
      Colon-26-10/F, grown in mice on a folate-depleted diet, was more sensitive to RTX
      and MTA (GDF, 2.1 and 1.3, respectively) but not to 5FU (GDF, 1.2); however,
      leucovorin reversed the effect leading to cures. Folate depletion did not reverse
      resistance of Colon-26A and Colon-26G (low TK) to MTA and RTX, whereas leucovorin
      only enhanced the 5FU effect in Colon-26A and Colon-26A/F. Folic acid at 15 mg/kg
      did not improve the therapeutic efficacy of MTA in folate-deficient mice. The
      folate-depleted diet decreased the reduced folates in Colon-26A/F and Colon-26
      G/F tumors less (4-5-fold; P < 0.01) than in Colon-26-10/F tumors (8-fold; P <
      0.001). Folate depletion increased TS levels 2-3-fold in all of the models and TK
      levels 6-fold (P < 0.01) in Colon-26G/F, explaining the lack of activity of MTA
      and RTX in Colon-26G/F. In contrast, TK-deficient FM3A/TK tumors were much more
      sensitive to RTX, MTA, and 5FU than parent FM3A tumors, which have comparable TS
      levels. The rate of thymidine phosphorylysis varied considerably in all of the
      tumors without a clear relation to antitumor activity. In conclusion, tumor
      folates may potentiate (5FU) or protect (antifolates). Murine tumor models should
      combine low folates and low thymidine rescue to optimize preclinical testing of
      antifolates.

PMID- 11325839
TI  - Intersection of interferon and hypoxia signal transduction pathways in nitric
      oxide-induced tumor apoptosis.
AB  - Activated macrophages play a central role in antitumor immunity. However, the
      stimuli that activate macrophages to kill tumor cells are not completely
      understood. Because the center of solid tumors can be hypoxic, we hypothesized
      that hypoxia may be an important signal in activating macrophages to kill tumor
      cells. Hypoxia stimulates IFN-primed macrophages to express the inducible nitric
      oxide synthase (NOS2) and to synthesize nitric oxide (NO). We show that this
      synergy between IFN and hypoxia is mediated by the direct interaction of the
      hypoxia inducible factor-1 (HIF-1) and IFN regulatory factor-1 (IRF-1), which are
      both required for the hypoxic transcription of NOS2. This interaction between HIF
      1 and IRF-1 may explain the mechanism by which macrophages infiltrating into
      tumors are activated to express NOS2 and to produce NO, a mediator of tumor
      apoptosis.

PMID- 11325840
TI  - Cyclophosphamide, doxorubicin, and paclitaxel enhance the antitumor immune
      response of granulocyte/macrophage-colony stimulating factor-secreting whole-cell
      vaccines in HER-2/neu tolerized mice.
AB  - Tumor-specific immune tolerance limits the effectiveness of cancer vaccines. In
      addition, tumor vaccines alone have a limited potential for the treatment of
      measurable tumor burdens. This highlights the importance of identifying more
      potent cancer vaccine strategies for clinical testing. We tested immune
      modulating doses of chemotherapy in combination with a granulocyte/macrophage
      colony stimulating factor (GM-CSF)-secreting, HER-2/neu (neu)-expressing whole
      cell vaccine as a means to treat existing mammary tumors in antigen-specific
      tolerized neu transgenic mice. Earlier studies have shown that neu transgenic
      mice exhibit immune tolerance to the neu-expressing tumors similar to what is
      observed in patients with cancer. We found that cyclophosphamide, paclitaxel, and
      doxorubicin, when given in a defined sequence with a GM-CSF-secreting, neu
      expressing whole-cell vaccine, enhanced the vaccine's potential to delay tumor
      growth in neu transgenic mice. In addition, we showed that these drugs mediate
      their effects by enhancing the efficacy of the vaccine rather than via a direct
      cytolytic effect on cancer cells. Furthermore, paclitaxel and cyclophosphamide
      appear to amplify the T helper 1 neu-specific T-cell response. These findings
      suggest that the combined treatment with immune-modulating doses of chemotherapy
      and the GM-CSF-secreting neu vaccine can overcome immune tolerance and induce an
      antigen-specific antitumor immune response. These data provide the immunological
      rationale for testing immune-modulating doses of chemotherapy in combination with
      tumor vaccines in patients with cancer.

PMID- 11325841
TI  - Cancer immunotherapy using a DNA vaccine encoding the translocation domain of a
      bacterial toxin linked to a tumor antigen.
AB  - Certain domains of bacterial toxins have been shown to facilitate translocation
      from extracellular and vesicular compartments into the cytoplasm. This feature
      represents an opportunity to enhance class I presentation of exogenous antigen to
      CD8(+) T cells. We investigated this notion by creating a novel fusion of the
      translocation domain (domain II) of Pseudomonas aeruginosa exotoxin A (ETA(dII))
      with a model tumor antigen, human papillomavirus type 16 E7, in the context of a
      DNA vaccine. Our in vitro studies indicated that cells transfected with
      ETA(dII)/E7 DNA or dendritic cells pulsed with lysates containing ETA(dII)/E7
      protein exhibited enhanced MHC class I presentation of E7 antigen. Vaccination of
      mice with ETA(dII)/E7 DNA generated a dramatic increase in the number of E7
      specific CD8(+) T cell precursors ( approximately 30-fold compared with wild-type
      E7 DNA) and converted a less effective DNA vaccine into one with significant
      potency against human papillomavirus type 16 E7-expressing murine tumors via a
      CD8-dependent pathway. These results indicate that fusion of the translocation
      domain of a bacterial toxin to an antigen may greatly enhance vaccine potency.

PMID- 11325842
TI  - Targeting dendritic cells to enhance DNA vaccine potency.
AB  - DNA vaccination that can induce both cellular and humoral immune responses has
      become an attractive immunization strategy against cancer and infection.
      Dendritic cells (DCs) play a critical role in the induction of immune responses
      by DNA vaccination. However, a major problem of DNA vaccination is its limited
      potency, because only a very limited fraction of injected DNA molecules are taken
      up by DCS: In this study, we describe a novel DNA vaccination strategy to enhance
      uptake and presentation of antigens by DCS: Specifically, we developed a DNA
      vaccine based upon expression of a model hepatitis B virus (HBV) e antigen fused
      to an IgG Fc fragment. After vaccination, the DNA are taken up by cells that
      produce and secrete the antigen-Fc fusion proteins. The secreted fusion proteins,
      in addition to inducing B cells, are efficiently captured and processed by DCs
      via receptor-mediated endocytosis and then presented to the MHC class II and as 
      I (cross-priming). The results of this study demonstrate that broad enhancement
      of antigen-specific CD4+ helper, CD8+ cytotoxic T-cell, and B-cell responses can
      be achieved by this DNA vaccination strategy. Thus, the strategy capable of
      inducing all arms of the adaptive immunity may provide a novel, generic design
      for the development of therapeutic and preventive DNA vaccines.

PMID- 11325843
TI  - Immunoscintigraphy with positron emission tomography: gallium-68 chelate imaging
      of breast cancer pretargeted with bispecific anti-MUC1/anti-Ga chelate
      antibodies.
AB  - Pretargeting techniques that are based on the sequential administrations of
      bispecific antitumor/antimetal chelate antibodies (BS-MAbs), a blocker to
      saturate the anti-chelate binding sites of the BS-MAb still present in the
      circulation, and the radiolabeled chelate are suitable to increase tumor-to
      normal tissue contrasts and enable positron emission tomography (PET) as an
      imaging method. As demonstrated in the nude mouse model, a combination of
      pretargeted immunoscintigraphy and PET markedly improved the detection of tumor
      xenografts. With the presented preliminary clinical trial, we attempted to assess
      the efficacy of pretargeting and PET for breast cancer localization in patients.
      The BS-MAb used for pretargeting was synthesized from the F(ab')(2) fragments of
      the anti-MUC1 MAb 12H12, which reacts with the vast majority of breast tumors,
      and the F(ab') fragments of an anti-gallium (Ga) chelate MAb via a mixed
      functional chemical linker. For labeling of the Ga-chelate, we used the short
      lived positron emitter Ga-68 (t(1/2), 68 min; beta(+), 88%). The dose and time
      schedule of pretargeting was deduced from previous animal experiments. Ten
      patients with biopsy-proven, primary breast carcinoma were infused with 10 mg of
      the BS-MAB: Eighteen h later, they received i.v. injections of 10.7 mg of a
      blocker and, 15 min later, 9.6 microg of the Ga chelate labeled with 230-300 MBq
      of (68)GA: PET imaging was started 60-90 min after injection of the (68)Ga
      chelate. Average tumor-to-blood and tumor:normal breast tissue ratios were 0.9
      and 3.0 at 1 h postinjection. Tumor uptake amounted to approximately 0.003% iD/g
      corresponding to a standard uptake value of approximately 2. Blood clearance of
      the (68)Ga chelate showed a t(1/2) beta of approximately 100 min. Fourteen of 17
      known lesions, averaging 25 +/- 16 mm in size, were clearly visualized as foci of
      increased activity with PET. No false-positive but three false-negative readings
      were obtained. An enhanced, bilateral activity uptake in the whole breast
      parenchyma, found in 4 of the 10 patients, compromised the recognition of these
      tumor sites. Although the shedding of the MUC1 antigen and the comparatively low
      tumor affinity of the BS-MAb, common to all anti-mucin MAbs, proved not to be
      optimal for increasing tumor:tissue ratios with a pretargeting technique, PET
      imaging offered better sensitivity for the detection of breast cancer at low
      tumor contrasts than conventional immunoscintigraphy. This could be demonstrated
      by the clear visualization of tumor sites 10 mm in size, which contrasted only by
      a factor of 2 from surrounding normal breast tissue.

PMID- 11325844
TI  - High frequency of cytolytic T lymphocytes directed against a tumor-specific
      mutated antigen detectable with HLA tetramers in the blood of a lung carcinoma
      patient with long survival.
AB  - We have identified an antigen recognized by autologous CTL on the lung carcinoma
      cells of a patient who enjoyed a favorable clinical evolution, being alive 10
      years after partial resection of the primary tumor. The antigenic peptide is
      presented by HLA-A2 molecules and encoded by a mutated sequence in the gene
      coding for malic enzyme, an essential enzyme that converts malate to pyruvate. In
      the tumor cell line derived from the patient, only the mutated malic enzyme
      allele is expressed, because of a loss of heterozygosity in the region of
      chromosome 6 that contains this locus. Tetramers of soluble HLA-A2 molecules
      loaded with the antigenic peptide stained approximately 0.4% of the patient's
      blood CD8 T cells. When these cells were stimulated in clonal conditions, 25% of
      them proliferated, and the resulting clones were lytic and specific for the
      mutated malic enzyme peptide. T-cell receptor analysis indicated that almost all
      of these antimalic CTLs shared the same receptor. Antimalic T cells were
      consistently found in blood samples collected from the patient between 1990 and
      1999, at frequencies ranging from 0.1 to 0.4% of the CD8 cells. Their frequency
      appeared to double within 2 weeks after intradermal inoculation of lethally
      irradiated autologous tumor cells. These results indicate that nonmelanoma cancer
      patients may also have a high frequency of blood CTLs directed against a tumor
      specific antigen.

PMID- 11325845
TI  - Enhanced activation of human T cells via avipox vector-mediated hyperexpression
      of a triad of costimulatory molecules in human dendritic cells.
AB  - T-cell activation usually requires at least two signals. The first signal is
      antigen-specific, and the second signal(s) involves the interaction of a T-cell
      costimulatory molecule(s) on the antigen-presenting cell (APC) with its ligand on
      the T cell. Dendritic cells (DCs) are the most potent APCs, attributable, in
      part, to their expression of several T-cell costimulatory molecules. Human DCs
      generated in vitro, however, will vary in methods of generation and maturation
      and in terms of expression of different phenotypic markers-including
      costimulatory molecules-among different donors. We report here that a recombinant
      avipox (fowlpox, rF) vector has been constructed that can efficiently express the
      transgenes for three human T-cell costimulatory molecules (B7-1, ICAM-1, and LFA
      3) as a result of individual early avipox promoters driving the expression of
      each transgene. This triad of costimulatory molecules (designated TRICOM) was
      selected because each has an individual ligand on T cells and each has been shown
      previously to prime a unique signaling pathway in T cells. We report here that rF
      TRICOM can efficiently infect human DCs of different states of maturity and
      hyperexpress each of the three costimulatory molecules on the DC surface without
      affecting other DC phenotypic markers. Infection of influenza or human papilloma
      virus 9-mer peptide-pulsed DCs from different individuals, or at different stages
      of maturity with rF-TRICOM, resulted in enhanced activation of T cells from
      peripheral blood mononuclear cells of autologous donors after 24 h of incubation
      with DCS: This enhanced activation was analyzed by both titrating the peptide and
      differing the DC:effector cell ratios. No effect was observed using the control
      wild-type avipox vector. No increase in apoptosis was observed in T cells
      hyperstimulated with the TRICOM vector, and no decrease in interleukin-12
      production was seen in lipopolysaccharide-stimulated DCs infected with rF-TRICOM.
      Antibody-blocking experiments demonstrated that enhanced T-cell activation by
      TRICOM was attributed to each of the three costimulatory molecules. Peptide
      pulsed, rF-TRICOM-infected DCs were also shown to be more effective than peptide
      pulsed DCs in activating T cells to 9-mer peptides derived from two relatively
      weak "self" immunogens, i.e., human prostate-specific antigen and human
      carcinoembryonic antigen. These studies thus demonstrate for the first time that
      a vector that can simultaneously hyperexpress three costimulatory molecules can
      be used to efficiently infect human DCs, leading to enhanced peptide-specific T
      cell activation. The use of this approach for in vitro studies and clinical
      applications in immunotherapy is discussed.

PMID- 11325846
TI  - Interleukin 18 transfection enhances antitumor immunity induced by dendritic cell
      tumor cell conjugates.
AB  - Dendritic cell (DC)-based tumor vaccine represents a promising approach to the
      immunotherapy of malignant tumors. We prepared a novel type of DC-based vaccine,
      stable conjugates of DCs and EL4 cells transduced with cDNA of OVA (E.G7).
      Immunization with DC-E.G7 conjugates led to generation of T helper (Th) 1
      cytokine-producing cells, antigen-specific CD8(+) T cells, and strong antitumor
      immunity that is dependent on both CD4(+) T cells and CD8(+) T cells. To further
      increase the potency of the vaccine, interleukin 18-transfected DCs were used to
      prepare the IL18DC-E.G7 conjugates. Immunization with such conjugates
      significantly increased the production of Th1 cytokine-producing cells and the
      number of antigen-specific CD8(+) T cells, as well as stronger antitumor
      immunity. Furthermore, the increased Th1 cytokine production and stronger
      antitumor effect were not observed in mice depleted of IFN-gamma. These data
      indicated that DC-tumor cell conjugates are a potent tumor vaccine. Interleukin
      18 can be administrated using gene-transfected cells and enhances antitumor
      immunity, which is mainly mediated by IFN-gamma.

PMID- 11325847
TI  - Growth and gene expression profile analyses of endometrial cancer cells
      expressing exogenous PTEN.
AB  - The PTEN tumor suppressor gene encodes a multifunctional phosphatase that plays
      an important role in inhibiting the phosphatidylinositol-3-kinase pathway and
      downstream functions that include activation of Akt/protein kinase B, cell
      survival, and cell proliferation. Enforced expression of PTEN in various cancer
      cell lines decreases cell proliferation through arrest of the cell cycle,
      accompanied in some cases by induction of apoptosis. We used cDNA microarrays
      containing 4009 cDNAs to examine changes in gene-expression profiles when
      exogenous PTEN was induced in PTEN-defective cells. The microarrays and
      subsequent semi-quantitative reverse transcription-PCR analysis revealed
      transcriptional stimulation of 99 genes and repression of 72 genes. Some of the
      differentially expressed genes already had been implicated in cell proliferation,
      differentiation, apoptosis, or cell cycle control, e.g., overexpression of PTEN
      induced transactivation of cyclin-dependent inhibitor 1B (p27Kip1) and 2B
      (p15INK4B), members of the TNF receptor family, tumor necrosis factor-associated
      genes, and members of the Notch-signaling and Mad families. To our knowledge this
      is the first report of transactivation of those genes by PTEN. The genes
      differentially expressed in our experiments also included many whose correlation
      with cancer development had not been recognized before. Our data should
      contribute to a greater understanding of the broad spectrum of ways in which PTEN
      affects intracellular signaling pathways. Analysis of expression profiles with
      microarrays appears to be a powerful approach for identifying anticancer genes
      and/or disease-specific targets for cancer therapy.

PMID- 11325848
TI  - Metastasis-associated differences in gene expression in a murine model of
      osteosarcoma.
AB  - Despite advances in the management of osteosarcoma (OSA) and other solid tumors,
      the development of metastasis continues to be the most significant problem and
      cause of death for cancer patients. To define genetic determinants of pulmonary
      metastasis, we have applied cDNA microarrays to a recently described murine model
      of OSA that is characterized by orthotopic tumor growth, a period of minimal
      residual disease, spontaneous pulmonary metastasis, and cell line variants that
      differ in metastatic potential. Microarray analysis defined 53 genes (of 3166
      unique cDNAs) that were differentially expressed between the primary tumors of
      the more aggressive (K7M2) and less aggressive (K12) OSA models. By review of the
      literature, these differentially expressed genes were assigned to six nonmutually
      exclusive metastasis-associated categories (proliferation and apoptosis, motility
      and cytoskeleton, invasion, immune surveillance, adherence, and angiogenesis).
      Functional studies to evaluate K7M2 and K12 for differences in each of these
      metastasis-associated processes revealed enhanced motility, adherence, and
      angiogenesis in the more aggressive K7M2 model. For this reason, 10 of the 53
      differentially expressed genes that were assigned to the motility and
      cytoskeleton, adherence, and angiogenesis categories were considered as most
      likely to define differences in the metastatic behavior of the two models. Ezrin,
      a gene not described previously in OSA, with functions in motility, invasion, and
      adherence, was 3-fold overexpressed in K7M2 compared with K12 by microarray.
      Differential expression for RNA was confirmed by Northern analysis and for
      protein by immunostaining. Alterations in ezrin protein levels and concomitant
      cytoskeletal changes in our model confirmed predictions from the arrays. The
      potential relevance of ezrin in OSA was suggested by its expression in five of
      five human OSA cell lines. This work represents a rationale approach to the
      evaluation of microarray data and will be useful to identify genes that may be
      causally associated with metastasis.

PMID- 11325849
TI  - Trp-p8, a novel prostate-specific gene, is up-regulated in prostate cancer and
      other malignancies and shares high homology with transient receptor potential
      calcium channel proteins.
AB  - We have identified and cloned a novel gene, trp-p8, by screening a prostate
      specific subtracted cDNA library. The 5694-bp cDNA has a 3312-bp open reading
      frame, which codes for a 1104 amino acid putative protein with seven
      transmembrane domains. The predicted protein revealed significant homology with
      the transient receptor potential (trp) family of Ca(2+) channel proteins.
      Northern blot analysis indicated that trp-p8 expression within normal human
      tissues is mostly restricted to prostate epithelial cells. In situ hybridization
      analysis showed that trp-p8 mRNA expression was at moderate levels in normal
      prostate tissue and appears to be elevated in prostate cancer. Notably, trp-p8
      mRNA was also expressed in a number of nonprostatic primary tumors of breast,
      colon, lung, and skin origin, whereas transcripts encoding trp-p8 were hardly
      detected or not detected in the corresponding normal human tissues.

PMID- 11325850
TI  - Tumor necrosis factor alpha polymorphism associated with increased susceptibility
      to development of adult T-cell leukemia/lymphoma in human T-lymphotropic virus
      type 1 carriers.
AB  - Human T-lymphotropic virus type 1 (HTLV-1) is etiologically associated with adult
      T-cell leukemia/lymphoma (ATL). Nevertheless, most individuals infected with HTLV
      1 do not develop ATL. To attempt to identify genetic factors promoting the
      progression to ATL, we investigated in HTLV-1 carriers the relationship between
      susceptibility to ATL and several polymorphisms: the three "decreased
      detoxifying" polymorphisms in GSTM1, GSTT1, and CYP1A1, the "proapoptotic"
      polymorphism in BCL2, and the five "high-production" polymorphisms in tumor
      necrosis factor alpha (TNF-alpha) using PCR-based genotyping assays. ATL patients
      (n = 71) were younger than HTLV-1 carriers (n = 80; 57 +/- 12 versus 63 +/- 10
      years; P = 0.0017). MALE:female ratio in ATL patients was higher than in carriers
      (52:19 versus 19:61, respectively; P < 0.0001), probably reflecting a higher
      incidence of HTLV-1 infection in females and a higher incidence of development of
      ATL in males. We found that the frequency of the TNF-alpha-857T allele, reported
      to be associated with high transcriptional activity of the promoter/enhancer
      region of the TNF-alpha gene, was enriched in individuals with ATL compared with
      healthy carriers (18.3% versus 8.8%, respectively; odds ratio, 2.34; 95%
      confidence interval, 1.2-4.7). None of the other four TNF-alpha polymorphisms was
      a significant indicator of risk of development of ATL, although odds ratios (ATL
      versus carrier) of all of the TNF-alpha polymorphisms were higher than 1.0.
      Furthermore, analysis of polymorphisms for GSTM1, GSTT1, CYP1A1, and BCL2 showed
      no significant difference between ATL patients and healthy carriers. Genetic
      polymorphism leading to increased TNF-alpha production may enhance susceptibility
      to ATL among HTLV-1 carriers. Alternatively, but less likely, the HLA loci might
      be an important factor because the TNF-alpha gene lies within the class III
      region of the MHC; however, the 857T allele is not in linkage disequilibrium with
      HLA alleles associated with ATL development.

PMID- 11325851
TI  - Hypermutability to ionizing radiation in mismatch repair-deficient, Pms2 knockout
      mice.
AB  - DNA mismatch repair (MMR) has been shown to play a role in the cytotoxicity of
      ionizing radiation (IR), as cell lines established from MMR-deficient mice
      exhibit higher clonogenic survival after IR than do cell lines from wild-type
      littermates. To test whether this tolerance phenotype would render MMR-deficient
      animals hypermutable to IR, we compared IR mutagenesis of Pms2-deficient versus
      wild-type transgenic mice carrying a lambda shuttle vector for mutation
      detection. In Pms2 nullizygous animals, the mutation frequency in the supFG1
      reporter gene was increased from 210 x 10(-5) in untreated animals to 734 x 10(
      5) after 6 Gy of IR (an increase of 524 mutants per 10(5)), whereas the frequency
      in wild-type mice increased from 1.9 x 10(-5) to 10.2 x 10(-5) (an increase of
      only 8.3 mutants per 10(5)). Similarly, when the lambda cII gene was used as a
      reporter, the mutation frequency in nullizygous mice was increased from 16.3 x
      10(-5) to 42.3 x 10(-5) after IR (an increase of 26.0 x 10(-5)), whereas the
      frequency in wild-type mice increased from 2.4 x 10(-5) to 9.4 x 10(-5) (an
      increase of only 7.0 x 10(-5)). The pattern of IR-induced mutations in the MMR
      deficient animals was notable for single bp deletions and insertions in
      mononucleotide repeat sequences, along with a slight increase in transversions.
      Overall, these results suggest that MMR-deficiency confers hypermutability to IR,
      and that much of this hypermutability can be attributed to induced instability of
      simple sequence repeats. Hence, MMR influences not only the survival but also the
      mutability of cells in response to IR.

PMID- 11325852
TI  - Ablation of p21waf1cip1 expression enhances the capacity of p53-deficient human
      tumor cells to repair UVB-induced DNA damage.
AB  - During periods of genotoxic stress, the cyclin-dependent kinase inhibitor
      p21waf1cip1 (hereafter referred to as p21) is transcriptionally up-regulated by
      the p53 tumor suppressor and subsequently plays a key role in cellular growth
      arrest. Investigations have also indicated that p21 may regulate nucleotide
      excision repair, a critical pathway that removes carcinogenic DNA damage induced
      by UV light and other mutagens. In this study, we examined whether low levels of
      endogenous p21 expression can modulate nucleotide excision repair in p53
      deficient human tumor cells after UVB exposure. For this purpose, we used the
      well-characterized p53-/-p21+/+ adenocarcinoma cell strain DLD1 and its isogenic
      counterpart carrying a homozygous knockout for p21 (p53-/-p21-/- DLD1). Because
      p53-/-p21+/+ DLD1 expresses very low levels of endogenous p21 protein that are
      not up-regulated after mutagen exposure, this strain has been considered
      functionally p21-deficient in the cellular response to DNA damage. Nonetheless,
      the ligation-mediated PCR technology was used here to demonstrate, at nucleotide
      resolution, that p53-/-p21+/+ DLD1 excises UVB-induced cyclobutane pyrimidine
      dimers from the c-jun proto-oncogene at a significantly lower rate than the
      isogenic p53-/-p21-/- derivative. The higher efficiency of DNA repair in UVB
      exposed p53-/-p21-/- DLD1 cells is accompanied by increased clonogenic survival
      and reduced levels of apoptosis, relative to the p53-/-p21+/+ counterpart. Our
      results show that ablation of p21 expression can significantly enhance the
      capacity of p53-deficient human tumor cells to repair UVB-induced DNA damage.

PMID- 11325853
TI  - Antitumor drug adozelesin differentially affects active and silent origins of DNA
      replication in yeast checkpoint kinase mutants.
AB  - The antitumor drug adozelesin is a potent cytotoxic DNA-damaging agent. Here we
      determined how adozelesin affects chromosomal DNA replication at a molecular
      level in a yeast model system and examined the influence of checkpoint kinase
      genes, the human homologues of which are mutated in cancer. Analysis of
      replication intermediates using two-dimensional gel electrophoresis showed that
      adozelesin inhibited the activity of a replication origin and stalled replication
      fork progression through chromosomal DNA at the origin. RAD53 and MEC1 protein
      kinase genes, homologues of human CHK2 and ATM, respectively, regulate an intra-S
      phase DNA damage checkpoint and, when mutated, permit unchecked replication of
      damaged DNA in S-phase. Mutations in these genes did not abrogate adozelesin
      induced inhibition of origin activity and fork progression at the replication
      origin. However, novel replication intermediates indicative of DNA breaks were
      detected only in the rad53 mutant, suggesting a role for the wild-type gene in
      maintaining chromosome integrity in the presence of the drug. In contrast to the
      inhibition of the active replication origin by adozelesin, normally silent
      origins present in the same chromosome were activated by adozelesin in rad53 and
      mec1 mutant cells. Thus, an antitumor drug that damages DNA can induce an
      abnormal replication pattern in a chromosome by activating silent origins,
      depending upon defects in yeast checkpoint kinase genes, the homologues of which
      are mutated in cancer. Implications of an abnormal replication pattern for the
      epigenetic regulation of gene expression are discussed.

PMID- 11325854
TI  - Genome-wide allelotyping analysis reveals multiple sites of allelic loss in
      gallbladder carcinoma.
AB  - Although gallbladder carcinoma (GBC) is a highly malignant neoplasm, there is
      very limited information about the molecular changes involved in its
      pathogenesis. To identify the chromosomal locations of putative tumor suppressor
      gene loci involved in the pathogenesis of GBC, we conducted a genome-wide
      allelotyping or loss of heterozygosity (LOH) analysis of GBCS: Microdissected
      tissue from 24 archival GBCs and their matched control DNAs were analyzed for PCR
      based LOH using 169 microsatellite markers spanning all nonacrocentric autosomal
      arms and the X chromosome. The chromosomal arms with the greatest frequencies of
      LOH (> or = 60%) were 3p, 6q, 7q, 8p, 9p, 9q, 11q, 12q, 17p, 18q, 19p, 22q, and
      XQ: The average fractional allele loss index in GBC cases was high (0.43) and
      frequent breakpoints were detected in gallbladder tumors. Of interest, 21
      different regions of frequent LOH (hot spots) defined as > or = 50% for
      individual GBC samples were detected in this neoplasm, nearly half of them
      confined to one microsatellite marker. We conclude that in GBC at least 21
      chromosomal regions with frequent allele losses are involved, suggesting that
      several putative tumor suppressor genes are inactivated in its pathogenesis.
      Overall, these data provide global estimates of the extent of genetic changes
      leading to GBC and will be useful for the identification of new tumor suppressor
      genes and for multiple new markers for translational research.

PMID- 11325855
TI  - Short mononucleotide repeat sequence variability in mismatch repair-deficient
      cancers.
AB  - Mismatch repair-deficient cancers are characterized by widespread insertions and
      deletions in microsatellite sequences, including those comprised of
      mononucleotide repeats. Such alterations have been observed in relatively short
      mononucleotide tracts in several genes and often are interpreted to indicate that
      the affected genes normally act as tumor suppressors. To aid in the
      interpretation of such changes, we have systematically assessed their frequency
      within transcribed regions of the genome that are unlikely to play a tumorigenic
      role. The advent of the complete human genomic sequences of chromosome 22 allowed
      us to select 29 genes for this analysis, spaced at approximately 1-Mb intervals.
      Each of the selected genes had an (A)(8) or a (G)(8) tract deep within intronic
      sequences that was not included in the processed transcript. Surprisingly, we
      found that there was substantial variation in the prevalence of mutations among
      these tracts. Some tracts were altered in < 5% of the mismatch repair-deficient
      cancers studied, whereas other tracts were altered in nearly half of the cancers.
      In particular, (G)(8) tracts were considerably more prone to mutation than (A)(8)
      tracts, and the sequences or chromatin structures surrounding the mononucleotide
      tracts seemed to affect their mutability significantly.

PMID- 11325856
TI  - Isolation of a novel candidate oncogene within a frequently amplified region at
      3q26 in ovarian cancer.
AB  - Amplification of 3q25-q26 was one of the most frequent chromosomal alterations in
      human ovarian carcinoma. A chromosome microdissection-hybrid selection method was
      applied to isolate transcribed sequences from a primary ovarian cancer containing
      high-copy-number amplification of 3q26 using 3q26 band-specific DNAs generated by
      chromosome microdissection. Using this method, we have isolated a novel candidate
      oncogene eIF-5A2 (eukaryotic initiation factor 5A2). eIF-5A2 shares 82% identity
      of amino acid sequence with eIF-5A including the minimum domain needed for eIF-5A
      maturation by hypusine modification at lysine-50 residue. Amplification and
      overexpression of eIF-5A2 was frequently detected in primary ovarian cancers and
      ovarian cancer cell lines. The proliferation-related function of eIF-5A supports
      that eIF-5A2 is a candidate oncogene related to the development of ovarian
      cancer.

PMID- 11325857
TI  - Roles of IKK kinases and protein kinase CK2 in activation of nuclear factor
      kappaB in breast cancer.
AB  - Nuclear factor-kappaB (NF-kappaB)/Rel transcription factors regulate genes that
      control cell proliferation, survival, and transformation. In normal breast
      epithelial cells, NF-kappaB/Rel proteins are mainly sequestered in the cytoplasm
      bound to one of the specific inhibitory IkappaB proteins, whereas in breast
      cancers they are activated aberrantly. Human breast tumor cell lines, carcinogen
      transformed mammary epithelial cells, and the majority of primary human or rodent
      breast tumor tissue samples express constitutively high levels of nuclear NF
      kappaB/REL: To begin to understand the mechanism of this aberrant NF-kappaB/Rel
      expression, in this study we measured the activity of the major kinases
      implicated in regulation of IkappaB stability, namely IKKalpha, IKKbeta, and
      protein kinase, CK2 (formerly casein kinase II). Hs578T, D3-1, and BP-1 breast
      cancer cell lines displayed higher levels of IKKalpha, IKKbeta, and CK2 activity
      than untransformed MCF-10F mammary epithelial cells. Inhibition of IKK activity
      upon expression of dominant negative kinases or of CK2 activity by treatment with
      selective inhibitors decreased NF-kappaB/Rel activity in breast cancer cells.
      Inactivation of the IkappaB kinase complex in Hs578T cells via expression of a
      dominant negative IKKgamma/NF-kappaB essential modulator/IKK-associated protein 1
      reduced soft agar colony growth. Thus, the aberrant expression of CK2 or IKK
      kinases promotes increased nuclear levels of NF-kappaB/Rel and transformation of
      breast cancer cells. Furthermore, primary human breast cancer specimens that
      displayed aberrant constitutive expression of NF-kappaB/Rel were found to exhibit
      increased CK2 and/or IKK kinase activity. These observations suggest these
      kinases play a similar role in an intracellular signaling pathway that leads to
      the elevated NF-kappaB/Rel levels seen in primary human mammary tumors and,
      therefore, represent potential therapeutic targets in the treatment of patients
      with breast cancer.

PMID- 11325858
TI  - N-cadherin-mediated intercellular interactions promote survival and migration of
      melanoma cells.
AB  - During melanoma development, loss of functional E-cadherin accompanies gain of
      expression of N-cadherin. The present study was carried out to investigate the
      functional significance of N-cadherin in melanoma cells. N-Cadherin mediated
      homotypic aggregation among melanoma cells as well as heterotypic adhesion of
      melanoma cells to dermal fibroblasts and vascular endothelial cells. Blocking of
      N-cadherin-mediated intercellular interaction by N-cadherin-specific antibodies
      increased the number of cells undergoing apoptosis. N-Cadherin-mediated cell
      adhesion-activated antiapoptotic protein Akt/PKB and subsequently increased beta
      catenin and inactivated the proapoptotic factor BAD: Furthermore, N-cadherin
      promoted migration of melanocytic cells over dermal fibroblasts, suggesting that
      N-cadherin may also play a role in metastasis. Together, these results indicate
      that the cadherin subtype switching from E- to N-cadherin during melanoma
      development not only frees melanocytic cells from the control by keratinocytes
      but also provides growth and possibly metastatic advantages to melanoma cells.

PMID- 11325859
TI  - Astrocyte-specific expression of activated p21-ras results in malignant
      astrocytoma formation in a transgenic mouse model of human gliomas.
AB  - Activation of the p21-ras signaling pathway from aberrantly expressed receptors
      promotes the growth of malignant human astrocytomas. We developed a transgenic
      mouse astrocytoma model using the glial fibrillary acidic protein (GFAP) promoter
      to express oncogenic V(12)Ha-ras, specifically in astrocytes. The development of
      GFAP-immunoreactive astrocytomas was directly proportional to the level of
      V(12)Ha-ras transgene expression. Chimeras expressing high levels of V(12)Ha-ras
      in astrocytes died from multifocal malignant astrocytomas within 2 weeks, whereas
      those with moderate levels went to germ-line transmission. Ninety-five percent of
      these mice died from solitary or multifocal low- and high-grade astrocytomas
      within 2-6 months. These transgenic astrocytomas are pathologically similar to
      human astrocytomas, with a high mitotic index, nuclear pleomorphism,
      infiltration, necrosis, and increased vascularity. Derivative astrocytoma cells
      are tumorigenic upon inoculation in another host. The transgenic astrocytomas
      exhibit additional molecular alterations associated with human astrocytomas,
      including a decreased or absent expression of p16, p19, and PTEN as well as
      overexpression of EGFR, MDM2, and CDK4. Cytogenetic analysis revealed consistent
      clonal aneuploidies of chromosomal regions syntenic with comparable loci altered
      in human astrocytomas. Therefore, this transgenic mouse astrocytoma model
      recapitulates many of the molecular histopathological and growth characteristics
      of human malignant astrocytomas in a reproducible, germ-line-transmitted, and
      high-penetrance manner.

PMID- 11325860
TI  - Human papillomavirus type 16 E6 and E7 cooperate to increase epidermal growth
      factor receptor (EGFR) mRNA levels, overcoming mechanisms by which excessive EGFR
      signaling shortens the life span of normal human keratinocytes.
AB  - Epidermal growth factor receptor (EGFR) levels are dramatically increased in
      human keratinocytes (HKc) immortalized with full-length human papillomavirus type
      16 (HPV16) DNA (HKc/HPV16), but increases in EGFR levels actually precede
      immortalization. In some normal HKc strains, acute expression of HPV16 E6 (but
      not HPV16 E5, HPV16 E7, or HPV6 E6) from LXSN retroviral vectors produced an
      increase in EGFR mRNA levels detectable at 24 h and stable for up to 10 days
      after infection. However, about one-half of the individual normal HKc strains we
      analyzed proved unresponsive to E6 induction of EGFR mRNA despite the robust
      expression of E6 and degradation of p53. E6 responsiveness of normal HKc strains
      correlated inversely with initial EGFR levels: although HKc strains expressing
      relatively low basal EGFR levels grew poorly and tolerated the infection protocol
      with difficulty, they responded to E6 with an increase in EGFR mRNA and protein
      and with robust proliferation. However, those HKc strains expressing high basal
      EGFR levels grew well, but did not respond to E6 with increased EGFR levels or
      with proliferation. Immunostaining of paraffin-embedded foreskin tissue for the
      EGFR confirmed that there is an intrinsic interindividual variability of EGFR
      expression in HKC: These results prompted us to investigate the effects of
      overexpression of the EGFR in normal HKC: Infection of normal HKc with a LXSN
      retrovirus expressing the full-length human EGFR cDNA resulted in a dramatic
      reduction in growth rate and a shorter life span. Although acute expression (1-10
      days after infection) of HPV16 E7 alone did not induce the EGFR, acute expression
      of E6 and E7 together increased EGFR levels in normal HKc unresponsive to E6
      alone. Also, HKc infected with E7 alone expressed increased EGFR levels at early
      stages of extended life span (at passage 9 after infection), and HKc immortalized
      by HPV16 E7 alone expressed EGFR levels comparable with those of E6/E7
      immortalized cells. These results support a key role of the EGFR in HPV16
      mediated transformation of HKC: In addition, these data show that normal HKc do
      not tolerate excessive EGFR levels/signaling, and such intolerance must be
      overcome in order for HKc to become immortalized by HPV16. We conclude that both
      E6 and E7 contribute to increasing EGFR levels, but with different mechanisms:
      although E6 can increase EGFR levels, it cannot overcome the resistance of normal
      HKc to excessive EGFR signaling. On the other hand E7, which alone does not
      acutely increase EGFR mRNA or protein, allows for EGFR overexpression in normal
      HKC:

PMID- 11325861
TI  - Epithelial-stromal interactions and tumor progression: meeting summary and future
      directions.
AB  - The Epithelial-Stromal Interactions Workshop was organized with the purpose of
      accelerating progress in understanding the interrelationship between tumor cells
      and their microenvironment and applying this knowledge to the control of tumor
      progression. The format of the meeting was the presentation of brief reports that
      focused on concepts rather than specifics, with extensive discussion periods to
      identify the issues and barriers hindering progress in this area. This report
      summarizes the findings of this meeting, highlighting the intimate relationship
      between tumor cells and their environment and addressing the opportunities that
      manipulation of host-tumor interactions has for therapeutic intervention. Several
      specific recommendations are made to advance knowledge and progress in this
      field.

PMID- 11325862
TI  - In memoriam: James A. Miller (1915-2000).

PMID- 11325863
TI  - p53 and atherosclerosis.

PMID- 11325864
TI  - Opening of mitochondrial K(ATP) channels triggers cardioprotection. Are reactive
      oxygen species involved?

PMID- 11325865
TI  - Mechanisms of the dynamics of reentry in a fibrillating myocardium. Developing a
      genes-to-rotors paradigm.

PMID- 11325866
TI  - Nitric oxide insufficiency, platelet activation, and arterial thrombosis.
AB  - Nitric oxide (NO) was originally discovered as a vasodilator product of the
      endothelium. Over the last 15 years, this vascular mediator has been shown to
      have important antiplatelet actions as well. By activating guanylyl cyclase,
      inhibiting phosphoinositide 3-kinase, impairing capacitative calcium influx, and
      inhibiting cyclooxygenase-1, endothelial NO limits platelet activation, adhesion,
      and aggregation. Platelets are also an important source of NO, and this platelet
      derived NO pool limits recruitment of platelets to the platelet-rich thrombus. A
      deficiency of bioactive NO is associated with arterial thrombosis in animal
      models, individuals with endothelial dysfunction, and patients with a deficiency
      of the extracellular antioxidant enzyme glutathione peroxidase-3. This enzyme
      catalyzes the reduction of hydrogen and lipid peroxides, which limits the
      availability of these reactive oxygen species to react with and inactivate NO.
      The complex biochemical reactions that underlie the function and inactivation of
      NO in the vasculature represent an important set of targets for therapeutic
      intervention for the prevention and treatment of arterial thrombotic disorders.

PMID- 11325867
TI  - Cardiovascular proteomics: evolution and potential.
AB  - The development of proteomics is a timely one for cardiovascular research.
      Analyses at the organ, subcellular, and molecular levels have revealed dynamic,
      complex, and subtle intracellular processes associated with heart and vascular
      disease. The power and flexibility of proteomic analyses, which facilitate
      protein separation, identification, and characterization, should hasten our
      understanding of these processes at the protein level. Properly applied,
      proteomics provides researchers with cellular protein "inventories" at specific
      moments in time, making it ideal for documenting protein modification due to a
      particular disease, condition, or treatment. This is accomplished through the
      establishment of species- and tissue-specific protein databases, providing a
      foundation for subsequent proteomic studies. Evolution of proteomic techniques
      has permitted more thorough investigation into molecular mechanisms underlying
      cardiovascular disease, facilitating identification not only of modified proteins
      but also of the nature of their modification. Continued development should lead
      to functional proteomic studies, in which identification of protein modification,
      in conjunction with functional data from established biochemical and
      physiological methods, has the ability to further our understanding of the
      interplay between proteome change and cardiovascular disease.

PMID- 11325868
TI  - Evidence that Rho-kinase activity contributes to cerebral vascular tone in vivo
      and is enhanced during chronic hypertension: comparison with protein kinase C.
AB  - The small G protein Rho and its target Rho-kinase may participate in the
      mechanisms underlying vascular contractile tone via inhibition of myosin light
      chain phosphatase. The present study has tested the hypothesis that Rho-kinase
      activity normally contributes to cerebral vascular tone in vivo, and that this
      effect is augmented during chronic hypertension. Comparative studies also
      examined the role of protein kinase C (PKC) in regulation of cerebral artery
      tone. Two Rho-kinase inhibitors, Y-27632 (0.1 to 100 micromol/L) and HA1077 (1 to
      10 micromol/L), caused marked concentration-dependent increases in basilar artery
      diameter of anesthetized normotensive rats (Sprague-Dawley and Wistar-Kyoto [WKY]
      strains), as measured using a cranial window approach. By comparison, the
      selective PKC inhibitors calphostin C (0.01 to 0.5 micromol/L) and Ro 31-8220 (5
      micromol/L) had little or no effect on basilar artery diameter. Vasodilator
      responses to Y-27632 were unaffected by PKC inhibition or activation. In two
      models of chronic hypertension (spontaneously hypertensive rats and WKY rats
      treated with N-nitro-L-arginine methyl ester for 4 weeks), Y-27632 elicited
      cerebral vasodilator responses that were significantly greater than in control
      WKY rats (P<0.05), indicating that the chronically hypertensive state and not
      genetic factors contributed to the increased responses to Rho-kinase inhibition.
      PKC inhibition had no significant effect on basilar artery diameter in
      chronically hypertensive rats. These data suggest that Rho-kinase, but not PKC,
      activity contributes substantially to cerebral artery tone in vivo, and this
      effect is augmented in the cerebral circulation during chronic hypertension.

PMID- 11325869
TI  - Macrophage p53 deficiency leads to enhanced atherosclerosis in APOE*3-Leiden
      transgenic mice.
AB  - Cell proliferation and cell death (either necrosis or apoptosis) are key
      processes in the progression of atherosclerosis. The tumor suppressor gene p53 is
      an essential gene in cell proliferation and cell death and is upregulated in
      human atherosclerotic plaques, both in smooth muscle cells and in macrophages. In
      the present study, we investigated the importance of macrophage p53 in the
      progression of atherosclerosis using bone marrow transplantation in APOE*3-Leiden
      transgenic mice, an animal model for human-like atherosclerosis. APOE*3-Leiden
      mice were lethally irradiated and reconstituted with bone marrow derived from
      either p53-deficient (p53(-/-)) or control (p53(+/+)) donor mice. Reconstitution
      of mice with p53(-/-) bone marrow did not result in any hemopoietic abnormalities
      as compared with p53(+/+) transplanted mice. After 12 weeks on an atherogenic
      diet, APOE*3-Leiden mice reconstituted with p53(-/-) bone marrow showed a
      significant (P=0.006) 2.3-fold increase in total atherosclerotic lesion area as
      compared with mice reconstituted with p53(+/+) bone marrow. Although likely a
      secondary effect of the increased lesion area, p53(-/-) transplanted mice also
      showed significantly more lesion necrosis (necrotic index, 1.1+/-1.3 versus 0.2+/
      0.7; P=0.04) and lesion macrophages (macrophage area, 79.9+/-40.0 versus 39.7+/
      27.3x10(3) micrometer(2) per section; P=0.02). These observations coincided with
      a tendency toward decreased apoptosis (terminal deoxynucleotidyl transferase end
      labeling [TUNEL]-positive nuclei going from 0.42+/-0.39 to 0.14+/-0.15%,
      P=0.071), whereas the number of proliferating cells (5'-bromo-2'-deoxyuridine
      positive nuclei) was not affected (3.75+/-0.98 versus 4.77+/-2.30%; P=0.59).
      These studies indicate that macrophage p53 is important in suppressing the
      progression of atherosclerosis and identify a novel therapeutic target for
      regulating plaque stability.

PMID- 11325870
TI  - Angiotensin selectively activates a subpopulation of postganglionic sympathetic
      neurons in mice.
AB  - Angiotensin II (Ang II) increases renal sympathetic nerve activity in
      anesthetized mice before and after ganglionic blockade, suggesting that Ang II
      may directly activate postganglionic sympathetic neurons. The present study
      directly tested this hypothesis in vitro. Neurons were dissociated from aortic
      renal and celiac ganglia of C57BL/6J mice. Cytosolic Ca(2+) concentration
      ([Ca(2+)](i)) was measured with ratio imaging using fura 2. Ang II increased
      [Ca(2+)](i) in a subpopulation of sympathetic neurons. At a concentration of 200
      nmol/L, 14 (67%) of 21 neurons responded with a rise in [Ca(2+)](i). The Ang II
      type 1 (AT(1)) receptor blocker (losartan, 2 micromol/L) but not the Ang II type
      2 (AT(2)) receptor blocker (PD123,319, 4 micromol/L) blocked this effect. The Ang
      II-induced [Ca(2+)](i) increase was abolished by removal of extracellular Ca(2+)
      but not altered by depletion of intracellular Ca(2+) stores with thapsigargin.
      Ang II no longer elicited a [Ca(2+)](i) increase in the presence of lanthanum (25
      micromol/L). The specific N-type and L-type Ca(2+) channel blockers, omega
      conotoxin GVIA and nifedipine, respectively, significantly inhibited the Ang II
      induced [Ca(2+)](i) increase. The protein kinase C inhibitor H7 but not the
      protein kinase A inhibitor H89 blocked the response to Ang II. These results
      demonstrate that Ang II selectively activates a subpopulation of postganglionic
      sympathetic neurons in aortic-renal and celiac ganglia, triggering Ca(2+) influx
      through voltage-gated Ca(2+) channels. This effect is mediated through AT(1)
      receptors and requires the activation of protein kinase C. The activation of a
      subgroup of sympathetic neurons by Ang II may exert unique effects on kidney
      function in pathological states associated with elevated Ang II.

PMID- 11325871
TI  - beta-Adrenergic stimulation synchronizes intracellular Ca(2+) release during
      excitation-contraction coupling in cardiac myocytes.
AB  - To elucidate microscopic mechanisms underlying the modulation of cardiac
      excitation-contraction (EC) coupling by beta-adrenergic receptor (beta-AR)
      stimulation, we examined local Ca(2+) release function, ie, Ca(2+) spikes at
      individual transverse tubule-sarcoplasmic reticulum (T-SR) junctions, using
      confocal microscopy and our recently developed technique for release flux
      measurement. beta-AR stimulation by norepinephrine plus an alpha(1)-adrenergic
      blocker, prazosin, increased the amplitude of SR Ca(2+) release flux (J(SR)), its
      running integral (integralJ(SR)), and L-type Ca(2+) channel current (I(Ca)), and
      it shifted their bell-shaped voltage dependence leftward by approximately 10 mV,
      with the relative effects ranking I(Ca)> J(SR)>integralJ(SR). Confocal imaging
      revealed that the bell-shaped voltage dependence of SR Ca(2+) release is
      attributable to a graded recruitment of T-SR junctions as well as to changes in
      Ca(2+) spike amplitudes. beta-AR stimulation increased the fractional T-SR
      junctions that fired Ca(2+) spikes and augmented Ca(2+) spike amplitudes, without
      altering the SR Ca(2+) load, suggesting that more release units were activated
      synchronously among and within T-SR junctions. Moreover, beta-AR stimulation
      decreased the latency and temporal dispersion of Ca(2+) spike occurrence at a
      given voltage, delivering most of the Ca(2+) at the onset of depolarization
      rather than spreading it out throughout depolarization. Because the synchrony of
      Ca(2+) spikes affects Ca(2+) delivery per unit of time to contractile
      myofilaments, and because the myofilaments display a steep Ca(2+) dependence, our
      data suggest that synchronization of SR Ca(2+) release represents a heretofore
      unappreciated mechanism of beta-AR modulation of cardiac inotropy.

PMID- 11325872
TI  - Diazoxide-induced cardioprotection requires signaling through a redox-sensitive
      mechanism.
AB  - Diazoxide, a selective opener of the mitochondrial ATP-sensitive potassium
      channel, has been shown to elicit tolerance to ischemia in cardiac myocytes and
      in perfused heart. However, the mechanism of this cardioprotection is poorly
      understood. Because reactive oxygen species (ROS) are recognized as important
      intracellular signaling molecules and have been implicated in ischemic
      preconditioning, we examined diazoxide-induced ROS production in adult
      cardiomyocytes. Cells treated with 50 micromol/L diazoxide showed a 173% increase
      in ROS production relative to baseline. 5-Hydroxydecanoate was found to attenuate
      the diazoxide-induced increase in ROS generation. The diazoxide-induced increase
      in ROS also was abrogated by the addition of either the antioxidant N
      acetylcysteine (NAC) or N-mercaptopropionylglycine. We also examined the ability
      of NAC to block the protective effects of diazoxide in the perfused rat heart.
      After 20 minutes of global ischemia and 20 minutes of reflow, hearts perfused
      with 100 micromol/L diazoxide before ischemia showed significantly improved
      postischemic contractile function relative to untreated hearts (84% versus 29% of
      initial left ventricular developed pressure, respectively). Hearts treated with
      diazoxide in the presence of 4 mmol/L NAC recovered 53% of initial left
      ventricular developed pressure, whereas hearts treated with NAC alone recovered
      46% of preischemic function. Using (31)P NMR spectroscopy, we found that, similar
      to preconditioning, diazoxide significantly attenuated ischemia-induced
      intracellular acidification and enhanced post- ischemic recovery of
      phosphocreatine levels, both of which were blocked by cotreatment with NAC. These
      data suggest that the cardioprotective actions of diazoxide are mediated by
      generation of a pro-oxidant environment.

PMID- 11325873
TI  - Hypothesis for the initiation of vasomotion.
AB  - Vasomotion is the regular variation in tone of arteries. In our study, we suggest
      a model for the initiation of vasomotion. We suggest that intermittent release of
      Ca(2+) from the sarcoplasmic reticulum (SR, cytosolic oscillator), which is
      initially unsynchronized between the vascular smooth muscle cells, becomes
      synchronized to initiate vasomotion. The synchronization is achieved by an ion
      current over the cell membrane, which is activated by the oscillating Ca(2+)
      release. This current results in an oscillating membrane potential, which
      synchronizes the SR in the vessel wall and starts vasomotion. Therefore, the
      pacemaker of the vascular wall can be envisaged as a diffuse array of individual
      cytosolic oscillators that become entrained by a reciprocal interaction with the
      cell membrane. The model is supported by experimental data. Confocal [Ca(2+)](i)
      imaging and isometric force development in isolated rat resistance arteries
      showed that low norepinephrine concentrations induced SR-dependent unsynchronized
      waves of Ca(2+) in the vascular smooth muscle. In the presence of the
      endothelium, the waves converted to global synchronized oscillations of
      [Ca(2+)](i) after some time, and vasomotion appeared. Synchronization was also
      seen in the absence of endothelium if 8-bromo-cGMP was added to the bath. Using
      the patch-clamp technique and microelectrodes, we showed that Ca(2+) release can
      activate an inward current in isolated smooth muscle cells from the arteries and
      cause depolarization. These electrophysiological effects of Ca(2+) release were
      cGMP dependent, which is consistent with the possibility that they are important
      for the cGMP-dependent synchronization. Further support for the model is the
      observation that a short-lasting current pulse can initiate vasomotion in an
      unsynchronized artery as expected from the model.

PMID- 11325874
TI  - Impaired modulation of sympathetic vasoconstriction in contracting skeletal
      muscle of rats with chronic myocardial infarctions: role of oxidative stress.
AB  - Skeletal muscle perfusion during exercise is impaired in heart failure, but the
      underlying mechanisms are poorly understood. One possibility is that sympathetic
      vasoconstriction is enhanced in exercising muscle in heart failure as a result of
      impaired counterregulatory mechanisms that normally act to attenuate
      vasoconstrictor responses. In healthy animals, sympathetic vasoconstriction in
      contracting skeletal muscle is attenuated by endogenously produced nitric oxide
      (NO). Because the NO pathway may be dysfunctional in heart failure, we
      hypothesized that reduced NO in contracting muscle would result in enhanced
      sympathetic vasoconstriction. In sham rats and rats with chronic myocardial
      infarctions (MIs) produced by coronary artery ligation, we measured arterial
      pressure and femoral artery blood flow responses to sympathetic nerve stimulation
      (1, 2.5, and 5 Hz) in resting and contracting hindlimb. In resting hindlimb,
      sympathetic stimulation decreased femoral vascular conductance similarly in sham
      and MI rats. In contracting hindlimb, these vasoconstrictor responses were
      attenuated to a greater extent in sham than in MI rats. NO synthase inhibition
      enhanced sympathetic vasoconstriction in contracting hindlimb of sham, but not
      MI, rats. Conversely, infusion of L-arginine or a superoxide scavenger, tempol or
      tiron, attenuated sympathetic vasoconstriction in contracting hindlimb of MI
      rats. NO synthase expression was similar, but malondialdehyde (a marker of free
      radical damage) was greater in skeletal muscle from MI than from sham rats. These
      data suggest that impaired metabolic modulation of sympathetic vasoconstriction
      in contracting skeletal muscle of MI rats is a consequence of superoxide-mediated
      disruption of the NO pathway.

PMID- 11325875
TI  - Ceramide reduces endothelium-dependent vasodilation by increasing superoxide
      production in small bovine coronary arteries.
AB  - Ceramide serves as a second messenger in a variety of mammalian cells. Little is
      known regarding the role of ceramide in the regulation of vascular endothelial
      function. The present study was designed to determine whether ceramide affects
      endothelium-dependent vasodilation in coronary arteries and to explore the
      mechanism of action of ceramide. In isolated and pressurized small bovine
      coronary arteries, cell-permeable C(2)-ceramide (10(-)(5) mol/L) markedly
      attenuated vasodilator responses to bradykinin and A23187 (by 40% and 60%,
      respectively). In the presence of K(G)-nitro-L-arginine methyl ester, ceramide
      produced no further inhibition on the vasodilation induced by these vasodilators.
      Ceramide had no effect on DETA NONOate-induced vasodilation. By use of a
      fluorescence NO indicator (4,5-diaminofluorescein diacetate), intracellular NO
      was measured in the endothelium of freshly isolated small coronary arteries. It
      was found that ceramide significantly inhibited bradykinin-induced NO increase
      within endothelial cells. However, it had no effect on the activity of arterial
      or endothelial NO synthase. Pretreatment of the arteries with sodium
      dihydroxybenzene disulfonate (Tiron, 10(-)(3) mol/L), a cell-permeable superoxide
      scavenger, or polyethylene glycol superoxide dismutase (100 U/mL) largely
      restored the inhibitory effects of ceramide on the vasodilation and NO increase
      induced by bradykinin or A23187. Moreover, ceramide time-dependently increased
      intracellular superoxide (O(2)(-. )) in the endothelium, as measured by a
      fluorescent O(2)(-. )indicator, dihydroethidium. These results demonstrate that
      ceramide inhibits endothelium-dependent vasodilation in small coronary arteries
      by decreasing NO in vascular endothelial cells and that this decrease in NO is
      associated with increased O(2)(-. ) but not with the inhibition of NO synthase
      activity within these cells.

PMID- 11325876
TI  - Attenuation of hypoxic pulmonary vasoconstriction by endotoxemia requires 5
      lipoxygenase in mice.
AB  - Sepsis and endotoxemia impair hypoxic pulmonary vasoconstriction (HPV), thereby
      reducing systemic oxygenation. To assess the role of leukotrienes (LTs) in the
      attenuation of HPV during endotoxemia, the increase in left lung pulmonary
      vascular resistance (LPVR) before and during left mainstem bronchus occlusion
      (LMBO) was measured in mice with and without a deletion of the gene encoding 5
      lipoxygenase (5-LO). LMBO increased the LPVR equally in saline-challenged wild
      type and 5-LO-deficient mice (96+/-20% and 94+/-19%, respectively). Twenty-two
      hours after challenge with Escherichia coli endotoxin, the ability of LMBO to
      increase LPVR was markedly impaired in wild-type mice (27+/-7%; P<0.05) but not
      in 5-LO-deficient mice (72+/-9%) or in wild-type mice pretreated with MK886, an
      inhibitor of 5-LO activity (76+/-10%). Compared with wild-type mice, endotoxin
      induced disruption of lung structures and inflammatory cell influx in the lung
      were markedly attenuated in 5-LO-deficient mice. Administration of MK571, a
      selective cysteinyl LT(1) receptor antagonist, 1 hour before endotoxin challenge
      preserved HPV and attenuated pulmonary injury in wild-type mice but did not
      prevent the endotoxin-induced increase in pulmonary myeloperoxidase activity.
      Taken together, these findings demonstrate that a 5-LO product, most likely a
      cysteinyl LT, contributes to the attenuation of HPV and to pulmonary injury after
      challenge with endotoxin.

PMID- 11325878
TI  - Point-of-care coagulation testing: stepping gently forward.

PMID- 11325877
TI  - Dynamics of intramural and transmural reentry during ventricular fibrillation in
      isolated swine ventricles.
AB  - The intramural dynamics of ventricular fibrillation (VF) remain poorly
      understood. Recent investigations have suggested that stable intramural reentry
      may underlie the mechanisms of VF. We performed optical mapping studies of VF in
      isolated swine right ventricles (RVs) and left ventricles (LVs). Nine RV walls
      were cut obliquely in their distal edge exposing the transmural surface. Six LV
      wedge preparations were also studied. Results showed that intramural reentry was
      present. In RV, 28 of 44 VF episodes showed reentry; 15% of the activation
      pathways were reentrant. Except for 4 episodes, reentry was transmural, involving
      subendocardial structures as the papillary muscle (PM) or trabeculae. In LV,
      reentry was observed in 27 of 27 VF episodes; 23% of the activations were part of
      reentrant pathways (P<0.05 compared with RV). All LV reentrant pathways were
      truly intramural (confined to the wall) and were frequently located at the PM
      insertion. In both ventricles, reentry was spatially and temporally unstable.
      Histological studies showed abrupt changes in fiber orientation at sites of
      reentry and wave splitting. Connexin 40 immunostaining demonstrated
      intramyocardial Purkinje fibers at sites of reentry in the PM root and around
      endocardial trabeculae. Our results confirm that reentry is frequent-but unstable
      in the myocardial wall during VF. In RV, reentry is mostly transmural and
      requires participation of subendocardial structures. The LV has a greater
      incidence of reentry and is intramural. Anisotropic anatomic structures played
      key roles in the generation of wave splitting and in the maintenance of reentry.

PMID- 11325879
TI  - Molecular manipulation of autoantibody testing in type 1 diabetes: two for one.

PMID- 11325880
TI  - Prodrug metabolites: implications for therapeutic drug monitoring.

PMID- 11325881
TI  - Improved method for diagnosis of Charcot-Marie-Tooth type 1a: patent pending?

PMID- 11325882
TI  - Molecular diagnosis of mycobacteria.
AB  - Tuberculosis is one of the leading infectious diseases in the world and is
      responsible for more than 2 million deaths and 8 million new cases annually.
      Because of the slow growth rate of the causative agent Mycobacterium
      tuberculosis, isolation, identification, and drug susceptibility testing of this
      organism and other clinically important mycobacteria can take several weeks or
      longer. During the past several years, many molecular methods have been developed
      for direct detection, species identification, and drug susceptibility testing of
      mycobacteria. These methods can potentially reduce the diagnostic time from weeks
      to days. Currently, two nucleic acid amplification methods, the Enhanced
      Mycobacterium tuberculosis Direct Test (Gen-Probe) and the Amplicor Mycobacterium
      tuberculosis Test (Roche Diagnostic Systems), have been approved by the Food and
      Drug Administration for direct detection of M. tuberculosis from clinical
      specimens. PCR-based sequencing has become commonly used to identify many
      mycobacterial species. DNA probes have been widely used for species determination
      of the most commonly encountered mycobacteria. High-density oligonucleotide
      arrays (DNA microarrays) also have been applied to simultaneous species
      identification and detection of mutations that confer rifampin resistance in
      mycobacteria.

PMID- 11325883
TI  - Immunoassay standardization: is it possible, who is responsible, who is capable?

PMID- 11325884
TI  - Enzymatic mutation detection method evaluated for detection of p53 mutations in
      cDNA from breast cancers.
AB  - BACKGROUND: Rapid, reproducible, and easily run methods with high sensitivity and
      specificity are required for mutation screening of clinical samples. We evaluated
      the Enzymatic Mutation Detection (EMD(TM)) method by analysis of archival cDNA
      from 203 breast cancer patients and comparison with results of cDNA-based
      sequencing of the tumor suppressor gene p53. METHODS: The EMD technology uses the
      T4 endonuclease VII, which cleaves double-stranded DNA at sites where a DNA
      mismatch is present because of mispairing or an insertion/deletion of
      nucleotides. The EMD analyses were carried out by dividing the p53 gene into two
      overlapping fragments that were analyzed separately. After PCR amplification, the
      fragments were hybridized with wild-type p53 and subsequently exposed to the EMD
      enzyme. Cleavage products were analyzed and scored using an ALF(TM) automated DNA
      sequencer and ALFwin Fragment Analyzer software (VER: 1.02). RESULTS: The EMD
      technique had sensitivities of 45% and 64% and specificities of 83% and 84% for
      the two fragments, respectively. Patients with EMD-positive, wild-type p53 tumors
      had a survival similar to that of patients with EMD-negative, wild-type p53
      tumors. Node-positive patients with p53 mutated tumors according to sequencing
      had a statistically significantly worse overall survival than those with p53 wild
      type tumors (P = 0.016), whereas this difference in survival was not detected
      when p53 status was determined with EMD (P = 0.47). CONCLUSIONS: EMD had
      insufficient sensitivity for consideration in screening for the p53 gene in this
      archival material. Sequencing must still be considered as the standard procedure.

PMID- 11325885
TI  - Polymorphic short tandem repeats for diagnosis of the Charcot-Marie-Tooth 1A
      duplication.
AB  - BACKGROUND: A 1.5-Mb microduplication containing the gene for peripheral myelin
      protein 22 (PMP22) on chromosome 17p11.2-12 is responsible for 75% of cases of
      the demyelinating form of Charcot-Marie-Tooth disease (CMT1A). Methods for
      molecular diagnosis of CMT1A use Southern blot and/or amplification by PCR of
      polymorphic poly(AC) repeats (microsatellites) located within the duplicated
      region, or the detection of junction fragments specific for the duplication.
      Difficulties with both strategies have led us to develop a new diagnostic
      strategy with highly polymorphic short tandem repeats (STRs) located inside the
      CMT1A duplicated region. METHODS: We tested 10 STRs located within the
      duplication for polymorphic behavior. Three STRs were selected and used to test a
      set of 130 unrelated CMT1A patients and were compared with nonduplicated
      controls. The study was then extended to a larger population of patients. Alleles
      of interest were sequenced. A manual protocol using polyacrylamide
      electrophoresis and silver staining and an automated capillary electrophoresis
      protocol to separate fluorescently labeled alleles were validated. RESULTS: We
      identified three new STRs covering 0.55 Mb in the center of the CMT1A
      duplication. One marker, 4A, is located inside the PMP22 gene. The two others, 9A
      and 9B, more telomerically positioned, have the highest observed heterozygosity
      reported to date for CMT1A markers: 0.80 for 9A, and 0.79 for 9B. Tetra- and
      pentanucleotide repeats offered clear amplification, accurate sizing, and easy
      quantification of intensities. CONCLUSIONS: Combined use of the three STRs allows
      robust diagnosis with almost complete informativeness. In our routine diagnosis
      for CMT1A, they have replaced the use of other polymorphic markers, either in a
      manual adaptation or combined with fluorescence labeling and allele sizing on a
      DNA sequencer.

PMID- 11325886
TI  - New polymorphic short tandem repeats for PCR-based Charcot-Marie-Tooth disease
      type 1A duplication diagnosis.
AB  - BACKGROUND: Charcot-Marie-Tooth disease type 1A (CMT1A) accounts for 70-90% of
      cases of CMT1 and is most frequently caused by the tandem duplication of a 1.4-Mb
      genomic fragment on chromosome 17p12. Molecular diagnosis of CMT1A has been based
      primarily on pulsed-field electrophoresis, fluorescence in situ hybridization,
      polymorphic allele dosage analysis, and quantitative PCR. We sought to improve
      the fidelity and applicability of PCR-based diagnosis by developing a panel of
      novel, highly polymorphic short tandem repeats (STRs) from within the CMT1A
      duplicated region. METHODS: We used a recently available genomic sequence to
      identify potentially polymorphic simple repeats. We then amplified these
      sequences in a multiethnic cohort of unaffected individuals and assessed the
      heterozygosity and number of alleles for each STR. Highly informative markers
      were then tested in a set of previously diagnosed CMT1A duplication patients, and
      the ability to identify the genomic duplication through the presence of three
      bands was assessed. RESULTS: We identified 34 polymorphic markers, 15 of which
      were suitable for CMT1A diagnosis on the basis of high heterozygosity in
      different ethnic groups, peak uniformity, and a large number of alleles. On the
      basis of the fluorescent dye and allele range of each marker, we developed two
      panels, each of which could be analyzed concurrently. Panel 1, which comprised 10
      markers, detected 37 of 39 duplications, whereas panel 2, which comprised the
      remaining 5 markers, identified 21 of 39 duplications. Through the combination of
      both panels, we identified 39 of 39 duplications in previously diagnosed CMT1A
      patients. CONCLUSIONS: The newly developed 15-marker set has the capability of
      detecting > 99% of duplications and thus is a powerful and versatile diagnostic
      tool.

PMID- 11325887
TI  - Quantification of HER2/neu gene amplification by competitive pcr using
      fluorescent melting curve analysis.
AB  - BACKGROUND: Molecular detection methods for HER2/neu gene amplification include
      fluorescence in situ hybridization (FISH) and competitive PCR. We designed a
      quantitative PCR system utilizing fluorescent hybridization probes and a
      competitor that differed from the HER2/neu sequence by a single base change.
      METHODS: Increasing twofold concentrations of competitor were coamplified with
      DNA from cell lines with various HER2/neu copy numbers at the HER2/neu locus.
      Competitor DNA was distinguished from the HER2/neu sequence by a fluorescent
      hybridization probe and melting curve analysis on a fluorescence-monitoring
      thermal cycler. The percentages of competitor to target peak areas on derivative
      fluorescence vs temperature curves were used to calculate copy number. RESULTS:
      Real-time monitoring of the PCR reaction showed comparable relative areas
      throughout the log phase and during the PCR plateau, indicating that only end
      point detection is necessary. The dynamic range was over two logs (2000-250 000
      competitor copies) with CVs < 20%. Three cell lines (MRC-5, T-47D, and SK-BR-3)
      were determined to have gene doses of 1, 3, and 11, respectively. Gene
      amplification was detected in 3 of 13 tumor samples and was correlated with
      conventional real-time PCR and FISH analysis. CONCLUSION: Use of relative peak
      areas allows gene copy numbers to be quantified against an internal competitive
      control in < 1 h.

PMID- 11325888
TI  - Fluorescence-based detection of the CETP TaqIB polymorphism: false positives with
      the TaqMan-based exonuclease assay attributable to a previously unknown gene
      variant.
AB  - BACKGROUND: Previous studies have shown an association between the TaqIB
      polymorphism of the cholesteryl ester transfer protein (CETP) gene with plasma
      CETP and HDL concentrations and the progression of coronary artery disease (CAD).
      The aim of the present study was to determine the performance of two new
      fluorescence-based detection systems in the analysis of the TaqIB genotype.
      METHODS: CAD patients (n = 150) with known TaqIB genotype, as determined by
      restriction fragment length polymorphism (RFLP) analysis, were selected,
      including three groups of 50 patients, carrying the B1/1, B1/2, and B2/2
      genotypes, respectively. The genotypes were also analyzed by fluorescence-based
      allele-specific TaqMan PCR and melting curve analysis (LightCycler). In addition,
      DNA sequencing was applied. RESULTS: The TaqIB genotypes obtained by fluorescence
      analysis corresponded to those determined by RFLP analysis with the exception of
      three heterozygous patients (B1/2), who were misclassified as homozygous B2
      carriers with the TaqMan system. Melting curve analysis of these samples
      demonstrated an additional melting point at 59.1 degrees C, which was also found
      in four patients homozygous for the B1 allele. DNA sequencing revealed a
      previously unknown C270T nucleotide exchange in intron 1 of the CETP gene, only
      nine base pairs from the TaqIB site. CONCLUSIONS: Determination of the TaqIB
      polymorphism with the TaqMan system led to misclassifications because of a
      previously unknown C270T polymorphism of the CETP gene. The base substitution was
      detected with the LightCycler because of the occurrence of an additional melting
      point. Our data indicate the importance of thorough evaluation of new gene
      analysis systems before using them on a routine basis.

PMID- 11325889
TI  - Evaluation of the TAS analyzer and the low-range heparin management test in
      patients undergoing extracorporeal membrane oxygenation.
AB  - BACKGROUND: The new Low-Range Heparin Management Test (LHMT), a method for point
      of-care testing (POCT) of heparinization, has been designed to function at the
      low to moderate heparin concentrations typically found in patients undergoing
      extracorporeal membrane oxygenation (ECMO). In this study, the new method is
      compared with two POCT methods and a laboratory-based anti-Xa assay. METHODS: We
      obtained 760 whole blood samples from 13 patients undergoing ECMO. All samples
      were tested immediately by the LHMT, the Activated Clotting Time (ACT) test, and
      its low-range counterpart (ACT-LR). Aliquots from the same blood draw were frozen
      for later anti-Xa analysis using the Diagnostica Stago method on the Roche Cobas
      Fara-II. RESULTS: The precision was best for duplicate citrated LHMT samples (CV
      = 3.1%). LHMT clotting times (overall median, 162 s) were typically shorter than
      ACT or ACT-LR times (247 and 235 s, respectively). The relationship between the
      LHMT and the other POCT methods differed significantly from patient to patient (P
      <0.0001), and a meaningful single relationship between the methods could not be
      obtained. The overall correlation coefficient between clotting time values and
      actual heparin concentrations was < or = 0.48 for each of the instruments tested,
      although time plots of each analyzer's data suggested that they detected heparin
      dosage changes within single patients. CONCLUSIONS: The performance of the LHMT
      on the TAS Analyzer is equivalent to that of currently commercially available
      POCT methods. The lack of agreement between absolute clotting time values and
      heparin concentrations suggests the need for reexamination of current ECMO
      patient management strategy.

PMID- 11325890
TI  - Development of a rapid and sensitive immunofluorometric assay for glutathione S
      transferase A.
AB  - BACKGROUND: The short half-life of the alpha-class glutathione S-transferases
      (GSTAs) in plasma combined with their even distribution throughout the liver
      lobule suggests that they may be useful complements to the more traditionally
      used liver markers. However, the currently available assays for measuring GSTAs
      in biological fluids have a poor dynamic range and are cumbersome, requiring
      multiple steps and prolonged incubation times. METHODS: Hybridomas that secrete
      monoclonal antibodies to human GSTAs were produced and used to develop a rapid
      one-step immunometric assay for the determination of GSTA in serum. The assay
      uses a time-resolved immunofluorometric assay (TR-IFMA) format and requires 35
      min of incubation. The reference interval was determined using 208 serum samples
      from healthy blood donors. We also compared our TR-IFMA with a commercially
      available enzyme immunoassay (EIA) for GSTAS: RESULTS: The assay had a detection
      limit of 0.07 microg/L with a measuring range up to 625 microg/L. Within-run
      imprecision (CV) was 1.8-2.6% over the concentrations of GSTA tested (2.5-311
      microg/L), with a between-run CV of <5%. In healthy blood donors, the median
      values and reference intervals were 2.0 microg/L and 0.6-7.2 microg/L for females
      and 2.6 microg/L and 0.7-9.8 microg/L for males, respectively. GSTA
      concentrations determined with the TR-IFMA correlated well with those obtained
      using a commercially available EIA. CONCLUSIONS: This report describes a new
      assay for monitoring the concentrations of GSTAs in human serum. The method may
      be useful in further evaluating the potential of monitoring serum GSTAs in the
      routine clinical setting.

PMID- 11325891
TI  - Quantification of cellular acid sphingomyelinase and galactocerebroside beta
      galactosidase activities by electrospray ionization mass spectrometry.
AB  - BACKGROUND: Diagnosis of Niemann-Pick (A and B) and Krabbe diseases is achieved
      by measurement of the lysosomal enzymes acid sphingomyelinase (ASM) and
      galactocerebroside beta-galactosidase (GCG), respectively. Conventional assays
      use radiolabeled or fluorescent substrates and do not allow simultaneous
      determination of two or more enzymes in the sample. METHODS: We developed a
      sensitive and specific method to assay ASM and GCG in skin fibroblast homogenates
      using biotinylated substrate conjugates. The products were purified by
      bioaffinity capture on streptavidin-agarose beads and, following release, were
      analyzed by electrospray ionization mass spectrometry. Quantification was
      achieved using stable-isotope-labeled internal standards that were chemically
      identical to the products of the enzymatic reactions. RESULTS: The method
      demonstrated excellent linearity of ASM and GCG enzymatic product formation with
      the amount of cellular protein and incubation time. The range of ASM activities
      in fibroblast lysates from six healthy patients was 39-70 nmol. mg(-1). h(-1)
      compared with 3.7-5.1 nmol. mg(-1). h(-1) in cell lysates from two patients
      affected with Niemann-Pick A disease. The GCG activities toward the corresponding
      substrate conjugate were 4.0-6.8 nmol. mg(-1). h(-1) in cell lysates from healthy
      patients compared with 0.1-0.2 nmol. mg(-1). h(-1) in cell lysates from two
      patients affected with Krabbe disease. The amounts of substrate conjugates needed
      per analysis were 15 nmol (14 microg) for both ASM and GCG. CONCLUSIONS:
      Electrospray mass spectrometry combined with the use of biotinylated substrate
      conjugates and bioaffinity purification represents a new approach for the
      diagnosis of lysosomal storage diseases as demonstrated for Niemann-Pick A and
      Krabbe diseases. No radioactive substrates are used, and the method uses a single
      instrumental platform to determine both ASM and GCG in one cell sample.

PMID- 11325892
TI  - C-Reactive protein concentrations and angiographic characteristics of coronary
      lesions.
AB  - BACKGROUND: C-Reactive protein (CRP) is a strong predictor of clinical outcome in
      coronary artery disease (CAD), and inflammation has been implicated in the
      process. We aimed to evaluate whether CRP concentrations measured with a new,
      automated particle-enhanced immunoturbidimetric method for high-sensitivity CRP
      may be related to specific high-risk angiographic features of coronary lesions.
      METHODS: In a cross-sectional study, we examined 103 consecutive patients
      undergoing cardiac catheterization for suspected CAD. We assessed the association
      of preprocedural CRP concentrations with clinical presentation (unstable angina)
      and angiographic features of coronary lesions. RESULTS: Twenty patients had
      unstable angina. Independent predictors of unstable angina included increased CRP
      [odds ratio (OR), 2.93 per 10-fold increase in CRP; 95% confidence interval (CI),
      1.28-6.69; P = 0.01] and the presence of macroscopic thrombus (OR, 7.08; 95% CI,
      1.33-37.8; P = 0.02). Thirty-two culprit lesions had macroscopic thrombus or
      eccentric/irregular discrete morphology without total occlusion. Increased CRP
      was the strongest predictor of such features (OR, 2.04 per 10-fold increase in
      CRP; 95% CI, 1.03-4.04; P = 0.04), and the effect was independent of the presence
      of unstable angina. CONCLUSIONS: Among patients with suspected CAD undergoing
      coronary angiography, increased CRP is strongly associated with unstable angina
      and with specific high-risk features of the culprit coronary lesions.

PMID- 11325893
TI  - Oxidative stress and homocysteine in coronary artery disease.
AB  - BACKGROUND: Oxidative stress is present in cardiovascular diseases (CVDs), and
      hyperhomocysteinemia, an independent risk factor for these diseases, may play a
      role by inducing production of oxygen free radicals. METHODS: To evaluate the
      possible role of homocysteine (Hcy) in inducing oxidative stress in coronary
      artery disease (CAD), plasma Hcy was measured in 68 consecutive cardiovascular
      patients, and plasma malondialdehyde (MDA), both free and total (free + bound),
      was measured in 40 patients with CAD (18 with chronic stable angina and 22 with
      unstable angina). As controls, we tested 70 healthy volunteers. Hcy was measured
      by an immunoenzymatic method and MDA, an index of lipid peroxidation, by gas
      chromatography-mass spectrometry. RESULTS: Plasma Hcy concentrations were
      significantly higher in cardiovascular patients than in controls (10.2 vs 8.9
      micromol/L; P <0.0002), with no significant difference between values in the
      stable and unstable angina subgroups. Similarly, total MDA was significantly
      higher in the CAD group than in the controls (2.6 vs 1.3 micromol/L; P <0.00001),
      again with no significant difference between stable and unstable angina patients.
      By contrast, free MDA, which was significantly higher in the CAD patients than
      the controls (0.4 vs 0.2 micromol/L; P < 0.00001), was also significantly higher
      in the unstable than in the stable angina group (0.5 vs 0.3 micromol/L; P <0.03).
      However, no correlation was observed among Hcy and free and total MDA.
      CONCLUSIONS: Our findings show that a moderate increase of Hcy is associated with
      CVD but that Hcy at the detected values cannot be considered completely
      responsible for oxidative damage. That lipid peroxidation is involved in CAD is
      shown by our observation of significantly increased plasma free and total MDA
      concentrations compared with controls. Moreover, free MDA values discriminated
      between unstable and chronic stable angina, and could thus represent a new
      diagnostic tool.

PMID- 11325894
TI  - Relationship between triglyceride concentrations and LDL size evaluated by
      malondialdehyde-modified LDL.
AB  - BACKGROUND: Hypertriglyceridemia is associated with decreased HDL-cholesterol
      (HDL-C) and increased small dense LDL. In addition, small dense LDL is known to
      be susceptible to oxidation. METHODS: We measured LDL particle size, using
      gradient gel electrophoresis, and malondialdehyde-modified LDL (MDA-LDL), using
      an ELISA, and investigated the association between triglyceride (TG)
      concentrations, LDL size, and MDA-LDL. RESULTS: TG concentrations correlated
      negatively with the predominant LDL size (r = -0.650) and HDL-C concentration (r
      = -0.556). The relationship between TG concentration and LDL size, evaluated by
      measuring MDA-LDL, distinguished subgroups derived from four subfractions of TG
      concentrations and four distribution ranges of LDL size. These experiments
      indicated that there is a threshold for oxidation susceptibility at an LDL size
      of 25.5 nm and a TG concentration of 1500 mg/L. To investigate the relationship
      between LDL size, MDA-LDL concentration, and other lipids (TGs, HDL-C,
      apolipoprotein B, and total cholesterol), we evaluated them in control subjects
      and patients with diabetes mellitus or hypertriglyceridemia. When the size range
      for normal LDL was postulated to be 25.5 < or = phi (LDL diameter) < 26.5 nm, the
      MDA-LDL concentration was significantly higher in the subgroups of patients with
      LDL in the size range 24.5 < or = phi < 25.5 nm compared with patients with
      normal LDL. This result also suggests that the threshold is at a LDL size of 25.5
      nm. CONCLUSION: The threshold for oxidation susceptibility coincided with the
      point of LDL size separation between the LDL subclass patterns A and B as an
      atherosclerotic risk.

PMID- 11325896
TI  - Glucuronidation of prodrug reactive site: isolation and characterization of
      oxymethylglucuronide metabolite of fosphenytoin.
AB  - BACKGROUND: This investigation was undertaken to identify the structure of a
      novel immunoreactive metabolite derived from fosphenytoin that has been
      hypothesized previously as present in sera from renally impaired patients
      receiving this prodrug. METHODS: The metabolite was isolated from uremic sera
      using solid-phase extraction and HPLC. Structural analysis was performed using
      HPLC-tandem mass spectrometry, nuclear magnetic resonance (NMR), deuterium
      exchange, and chemical derivatization. Immunoreactivity was evaluated using a
      fluorescence polarization immunoassay. RESULTS: The metabolite had a parent ion
      at m/z 457 in the negative-ion mode and fragmented to yield the m/z 251 of
      phenytoin, as well as other mass fragments of phenytoin. Mass fragments
      associated with glucuronic acid were also present. The chromatographic peak
      corresponding to this metabolite demonstrated immunoreactivity sufficient to lead
      to falsely increased reported values for phenytoin immunoassays. The observed
      immunoreactivity was also proportional to the relative concentration of the
      metabolite in collected fractions. Analysis by NMR indicated the presence of
      phenyl groups with chemical shifts identical to those of phenytoin, as well as
      the presence of a methylene bridge, which was consistent with the same methylene
      bridge present on the phosphate ester of fosphenytoin. Comparative analysis of
      serum samples from renally impaired patients receiving phenytoin vs fosphenytoin
      using multiple reaction monitoring quantification demonstrated that this
      metabolite was associated with fosphenytoin administration. CONCLUSIONS: A unique
      immunoreactive oxymethylglucuronide metabolite derived from fosphenytoin has been
      isolated from sera from uremic patients receiving this prodrug.

PMID- 11325895
TI  - Heparin-induced release of protein-bound solutes during hemodialysis is an in
      vitro artifact.
AB  - BACKGROUND: Several studies have pointed to a release of drugs or protein-bound
      solutes from their binding sites during heparinization. The effect is attributed
      to the metabolism of triglycerides to free fatty acids (FFAs), which compete with
      drugs for protein binding sites. This study evaluated the impact of intradialytic
      heparin on the free concentration of the uremic toxin p-cresol and on FFAS:
      METHODS: Blood samples from hemodialysis (HD) patients, before and during HD,
      were collected with selected anticoagulation strategies. We assessed the effects
      of standing time, temperature, pH, and the addition of a lipase inhibitor,
      tetrahydrolipstatin (THL) to blood samples on the free p-cresol concentration. p
      Cresol was analyzed by HPLC with fluorescence detection. We measured FFAs by gas
      chromatography, and the free fractions of added valproic acid and phenytoin were
      evaluated by fluorescence polarization immunoassay. RESULTS: In blood samples (n
      = 22) not submitted to a specific treatment, free p-cresol increased from 9.9 +/-
      5.1 to 31.9 +/- 22.3 micromol/L after 30 min of heparin HD (P < 0.001) and
      correlated significantly with FFAs (r = 0.80; P = 0.002; n = 12). There was no
      increase in free p-cresol during heparin-free HD (n = 6) and trisodium citrate HD
      (n = 9). In addition, p-cresol in ultrafiltrates (n = 3) did not correspond to
      the free p-cresol in heparinized blood, suggesting that the increase in free p
      cresol was artifactual. The release of p-cresol in the test tube was enhanced by
      standing time (n = 6), sample temperature (n = 6), and alkaline pH (n = 6).
      Inhibition of lipase activity with THL prevented the increase of FFAs (n = 6) and
      the release of free p-cresol during HD (n = 22). These results were corroborated
      by the study of the free fraction of valproic acid (n = 6) and phenytoin (n = 6).
      CONCLUSIONS: The free concentrations of protein-bound solutes in plasma of
      heparinized patients are influenced by external factors that alter the lipase
      activity in the test tube. The free fraction does not increase during HD when
      lipase activity is neutralized at the time of blood sampling, so that previously
      reported increases are probably artifacts.

PMID- 11325897
TI  - Evaluation of the performance and clinical impact of a rapid intraoperative
      parathyroid hormone assay in conjunction with preoperative imaging and concise
      parathyroidectomy.
AB  - BACKGROUND: (99m)Tc-sestamibi scans and rapid, intraoperative intact parathyroid
      hormone (PTH) assays allow preoperative identification of diseased glands and
      intraoperative confirmation of diseased gland removal, respectively. Use of these
      two new technologies may facilitate simpler, more concise surgery, shorter
      hospital stays, and decreased costs for frozen-section analysis. One major
      drawback to this new strategy has been the high cost of rapid point-of-care PTH
      assays. METHODS: We performed rapid PTH assays with the DPC Turbo PTH assay on
      the DPC IMMULITE automated analyzer. The number of intraoperative frozen
      sections, type of anesthesia, surgical approach, length of hospital stay, and pre
      and postoperative calcium values were compared between a group of 49 patients
      undergoing parathyroidectomy where the intraoperative PTH assay was used in
      conjunction with preoperative imaging, and a historical control group of 55
      patients before the use of these two technologies in our institution. RESULTS:
      Comparison of the Turbo PTH assay to the standard IMMULITE PTH assay gave the
      following: y = 1.08 x - 4.36 (r = 0.97; n = 48). For the 49 patients, the median
      turnaround time for each intraoperative PTH determination was 19 min (range, 14
      40 min). The median decrease in PTH values from baseline was 88% (range, 33-99%).
      Thirty-seven patients required two PTH determinations, 7 required three, 4 had
      four, and 1 required five determinations. The average laboratory cost for the
      rapid intraoperative PTH assays was < $100 per patient (range, $55 to $113).
      Compared with the control group, the experimental group had significantly fewer
      frozen sections (1.4 vs 2.5; P < 0.0001), shorter hospital stays (17 discharged
      on the day of surgery vs none discharged on the day of surgery; P < 0.0001),
      greater use of local anesthesia (33% vs 0%; P < 0.001), and more unilateral,
      rather than bilateral neck explorations (65% vs 0%; P < 0.001). CONCLUSIONS: The
      combination of intraoperative Turbo PTH assay and preoperative (99m)Tc-sestamibi
      scans can lead to significant decreases in laboratory and surgical pathology
      costs, hospital stays, and exposure to general anesthesia by facilitating concise
      parathyroidectomy surgery.

PMID- 11325898
TI  - Fusion proteins for combined analysis of autoantibodies to the 65-kDa isoform of
      glutamic acid decarboxylase and islet antigen-2 in insulin-dependent diabetes
      mellitus.
AB  - BACKGROUND: Prediction, risk assessment, and diagnosis of autoimmune diseases
      often rely on detection of autoantibodies directed to multiple target antigens,
      such as the 65-kDa isoform of glutamic acid decarboxylase (GAD65-abs) and the
      tyrosine phosphatase-like protein islet antigen-2 (IA2-abs), the two major
      subspecificities of islet cell antibodies (ICAs) associated with insulin
      dependent diabetes mellitus. We hypothesized that a combination of autoantigens
      in a fusion protein unifying the important immunodominant epitopes could provide
      an efficient target for cost-effective, one-step screening of sera. METHODS:
      Chimeric proteins composed of GAD65 and IA2 residues were constructed, analyzed
      for their immune reactivity with monoclonal antibodies and sera, and used in a
      diagnostic assay with (35)S-labeled protein as antigen. RESULTS: Length and order
      of GAD65 and IA2 sequences were critical for conservation of the conformational
      epitopes in the fusion protein. Among four chimera tested, only IA2((606
      979))/GAD65((1-585)) retained wild-type-like folding of GAD65 and IA2 domains and
      yielded a stable protein after baculovirus expression. Reactivity of GAD65
      antibody- and IA2 antibody-positive sera from patients newly diagnosed with
      insulin-dependent diabetes mellitus, from ICA-positive prediabetics, and from ICA
      positive first-degree relatives demonstrated conservation of the relevant
      autoreactive epitopes. The assay based on the in vitro translated fusion antigen
      had a sensitivity and specificity identical to those for detection of GAD65- and
      IA2-abs based on the two separate GAD65 and IA2 proteins. CONCLUSIONS:
      Autoantigens such as GAD65 and IA2 can be combined successfully in a fusion
      protein of similar immune reactivity. This allows simultaneous detection of GAD65
      and IA2-abs in a one-step screening assay and cost-effective identification of
      positive individuals at risk of diabetes or at onset of disease.

PMID- 11325899
TI  - Regression-based reference limits for serum transferrin receptor in children 6
      months to 16 years of age.

PMID- 11325900
TI  - Fetal DNA analyzed in plasma from a mother's three consecutive pregnancies to
      detect paternally inherited aneuploidy.

PMID- 11325901
TI  - Stability of serum beta-crosslaps during storage: influence of pH and storage
      temperature.

PMID- 11325902
TI  - Agreement of Owren and Quick prothrombin times: effects of citrate and calcium
      concentrations and international sensitivity index correction.

PMID- 11325903
TI  - Assay for hexosamine pathway intermediates (uridine diphosphate-N-acetyl amino
      sugars) in small samples of human muscle tissue.

PMID- 11325904
TI  - Liver-type arginase is a highly sensitive marker for hepatocellular damage in
      rats.

PMID- 11325905
TI  - Cerebrospinal fluid cytokeratins for diagnosis of patients with central nervous
      system metastases from breast cancer.

PMID- 11325906
TI  - Adaptation of an enzyme immunoassay to assess urinary cotinine in nonsmokers
      exposed to tobacco smoke.

PMID- 11325907
TI  - IgG autoantibodies against tissue transglutaminase in relation to antinuclear
      antibodies.

PMID- 11325908
TI  - S100b protein concentrations in amniotic fluid correlate with gestational age and
      with cerebral ultrasound scanning results in healthy fetuses.

PMID- 11325909
TI  - Phenotype determination of thiopurine methyltransferase in erythrocytes by HPLC.

PMID- 11325910
TI  - Detection of nucleotide c985 A-->G mutation of medium-chain acyl-CoA
      dehydrogenase gene by real-time PCR.

PMID- 11325911
TI  - New generation cardiac troponin I assay for the access immunoassay system.

PMID- 11325912
TI  - Troponin T and troponin I in carriers of Duchenne and Becker muscular dystrophy
      with cardiac involvement.

PMID- 11325913
TI  - Relationship between natriuretic peptide concentrations in plasma and posture
      during blood sampling.

PMID- 11325914
TI  - Evaluation of the Drew Scientific ds30 homocysteine assay in comparison with the
      Centers for Disease Control and prevention reference HPLC method.

PMID- 11325915
TI  - Capillary zone electrophoresis of proteins in body fluids: comparison of
      capillary and agarose gel electrophoresis.

PMID- 11325916
TI  - Management of maternal Amanita phalloides poisoning during the first trimester of
      pregnancy: a case report and review of the literature.
AB  - BACKGROUND: Amanita phalloides poisoning produces acute liver failure and often
      death. Maternal poisonings are rare, and medical decisions of abortion or liver
      transplantation in this critical situation frequently are based on laboratory
      data. We report here the case of a 22-year-old-woman in the 11th week of
      pregnancy, who ingested mushrooms. CASE REPORT: The patient's clinical symptoms
      (e.g., vomiting and diarrhea) and blood chemistry data (persistent increases of
      aspartate aminotransferase and alanine aminotransferase and severe decreases in
      prothrombin, factor V, factor II, factor VII, and factor X) indicated poisoning
      of medium severity. The management consisted of intravenous hydration, and
      administration of silymarine and N-acetylcysteine. No fetal damage was observed,
      and birth and development of the infant (now 2 years of age) proceeded without
      incident. CONCLUSION: Abortion is not necessarily indicated in maternal poisoning
      by A. phalloides, even in the first trimester of pregnancy.

PMID- 11325917
TI  - Pleural protein capillary electrophoresis for the separation of transudates and
      exudates.

PMID- 11325918
TI  - Correction of positive bias of the Roche Tina-quant II hemoglobin A1c (HbA1c)
      assay at low HbA1c percentages.

PMID- 11325919
TI  - alpha(1)-Antitrypsin deficiency as a result of compound heterozygosity for the Z
      and M(Heerlen) alleles.

PMID- 11325920
TI  - Lactic acid dimer: an artifact in the gas chromatographic analysis of urine with
      massive lactic acid aciduria.

PMID- 11325923
TI  - Divergence in fitness and evolution of drug resistance in experimental
      populations of Candida albicans.
AB  - The dissemination and persistence of drug-resistant organisms in nature depends
      on the relative fitness of sensitive and resistant genotypes. While resistant
      genotypes are expected to be at an advantage compared to less resistant genotypes
      in the presence of drug, resistance may incur a cost; resistant genotypes may be
      at a disadvantage in the absence of drug. We measured the fitness of replicate
      experimental populations of the pathogenic yeast Candida albicans founded from a
      single progenitor cell in a previous study (L. E. Cowen, D. Sanglard, D.
      Calabrese, C. Sirjusingh, J. B. Anderson, and L. M. Kohn, J. Bacteriol. 182:1515
      1522, 2000) and evolved in the presence, and in the absence, of the antifungal
      agent fluconazole. Fitness was measured both in the presence and in the absence
      of fluconazole by placing each evolved population in direct competition with the
      drug-sensitive ancestor and measuring the reproductive output of each competitor
      in the mixture. Populations evolved in the presence of drug diverged in fitness.
      Any significant cost of resistance, indicated by reduced fitness in the absence
      of drug, was eliminated with further evolution. Populations evolved in the
      absence of drug showed more uniform increases in fitness under both conditions.
      Fitness in the competition assays was not predicted by measurements of the MICs,
      doubling times, or stationary-phase cell densities of the competitors in
      isolation, suggesting the importance of interactions between mixed genotypes in
      competitions.

PMID- 11325924
TI  - Engineering a homo-ethanol pathway in Escherichia coli: increased glycolytic flux
      and levels of expression of glycolytic genes during xylose fermentation.
AB  - Replacement of the native fermentation pathway in Escherichia coli B with a homo
      ethanol pathway from Zymomonas mobilis (pdc and adhB genes) resulted in a 30 to
      50% increase in growth rate and glycolytic flux during the anaerobic fermentation
      of xylose. Gene array analysis was used as a tool to investigate differences in
      expression levels for the 30 genes involved in xylose catabolism in the parent
      (strain B) and the engineered strain (KO11). Of the 4,290 total open reading
      frames, only 8% were expressed at a significantly higher level in KO11 (P <
      0.05). In contrast, over half of the 30 genes involved in the catabolism of
      xylose to pyruvate were expressed at 1.5-fold- to 8-fold-higher levels in KO11.
      For 14 of the 30 genes, higher expression was statistically significant at the
      95% confidence level (xylAB, xylE, xylFG, xylR, rpiA, rpiB, pfkA, fbaA, tpiA,
      gapA, pgk, and pykA) during active fermentation (6, 12, and 24 h). Values at
      single time points for only four of these genes (eno, fbaA, fbaB, and talA) were
      higher in strain B than in KO11. The relationship between changes in mRNA (cDNA)
      levels and changes in specific activities was verified for two genes (xylA and
      xylB) with good agreement. In KO11, expression levels and activities were
      threefold higher than in strain B for xylose isomerase (xylA) and twofold higher
      for xylulokinase (xylB). Increased expression of genes involved in xylose
      catabolism is proposed as the basis for the increase in growth rate and
      glycolytic flux in ethanologenic KO11.

PMID- 11325925
TI  - Nitrogen or sulfur starvation differentially affects phycobilisome degradation
      and expression of the nblA gene in Synechocystis strain PCC 6803.
AB  - Nitrogen (N) limitation in cyanobacteria is well documented: a reduced growth
      rate is observed, accompanied by a cessation of phycobiliprotein synthesis and an
      ordered degradation of phycobilisomes (PBS). This leads to a dramatic bleaching
      phenomenon known as chlorosis. In Synechococcus strain PCC 7942, bleaching due to
      PBS degradation is also observed under sulfur (S) or phosphorus (P) limitation,
      and all three are under the control of the nblA gene product, a 59-amino-acid
      polypeptide which is overexpressed under N, S, and P starvation (J. L. Collier,
      and A. R. Grossman, EMBO J. 13:1039-1047, 1994). Cyanobase sequence data for
      Synechocystis strain PCC 6803 indicate the presence of two tandem open reading
      frames (sll0452 and sll0453) homologous to nblA. We cloned the two genes,
      identified a unique 5' mRNA end suggestive of a single transcription start site,
      and studied nblA expression under conditions of N or S starvation by Northern
      hybridization: transcripts were detected only under N starvation (no signal is
      detected in replete medium or with S starvation), whether nblA1 or nblA2 was used
      as a probe. Mutations in nblA1 and nblA2 were constructed by insertion of a
      kanamycin cassette; both mutations were nonbleaching under N starvation.
      Synechocystis strain PCC 6803 does not bleach under S starvation, consistent with
      the absence of nblA induction in these conditions. These results were confirmed
      by analysis of the PBS components: sequential degradation of phycocyanin and
      associated linkers was observed only under conditions of N starvation. This
      indicates differences between Synechocystis strain PCC 6803 and Synechococcus
      strain PCC 7942 in their regulatory and signaling pathways leading to N- and S
      starved phenotypes.

PMID- 11325926
TI  - Forespore-specific transcription of the lonB gene during sporulation in Bacillus
      subtilis.
AB  - The Bacillus subtilis genome encodes two members of the Lon family of prokaryotic
      ATP-dependent proteases. One, LonA, is produced in response to temperature,
      osmotic, and oxidative stress and has also been implicated in preventing sigma(G)
      activity under nonsporulation conditions. The second is encoded by the lonB gene,
      which resides immediately upstream from lonA. Here we report that transcription
      of lonB occurs during sporulation under sigma(F) control and thus is restricted
      to the prespore compartment of sporulating cells. First, expression of a lonB
      lacZ transcriptional fusion was abolished in strains unable to produce sigma(F)
      but remained unaffected upon disruption of the genes encoding the early and late
      mother cell regulators sigma(E) and sigma(K) or the late forespore regulator
      sigma(G). Second, the fluorescence of strains harboring a lonB-gfp fusion was
      confined to the prespore compartment and depended on sigma(F) production. Last,
      primer extension analysis of the lonB transcript revealed -10 and -35 sequences
      resembling the consensus sequence recognized by sigma(F)-containing RNA
      polymerase. We further show that the lonB message accumulated as a single
      monocistronic transcript during sporulation, synthesis of which required sigma(F)
      activity. Disruption of the lonB gene did not confer any discernible sporulation
      phenotype to otherwise wild-type cells, nor did expression of lonB from a
      multicopy plasmid. In contrast, expression of a fusion of the lonB promoter to
      the lonA gene severely reduced expression of the sigma(G)-dependent sspE gene and
      the frequency of sporulation. In confirmation of earlier observations, we found
      elevated levels of sigma(F)-dependent activity in a spoIIIE47 mutant, in which
      the lonB region of the chromosome is not translocated into the prespore.
      Expression of either lonB or the P(lonB)-lonA fusion from a plasmid in the
      spoIIIE47 mutant reduced sigma(F) -dependent activity to wild-type levels. The
      results suggest that both LonA and LonB can prevent abnormally high sigma(F)
      activity but that only LonA can negatively regulate sigma(G).

PMID- 11325927
TI  - Identification and characterization of a developmentally regulated protein, EshA,
      required for sporogenic hyphal branches in Streptomyces griseus.
AB  - To identify sporulation-specific proteins that might serve as targets of
      developmental regulatory factors in Streptomyces, we examined total proteins of
      Streptomyces griseus by two-dimensional gel electrophoresis. Among five proteins
      that were present at high levels during sporulation but absent from vegetative
      cells, two of the proteins, P3 and P4, were absent from developmental mutants
      that undergo aberrant morphogenesis. The deduced amino acid sequence of the gene
      that encodes P3 (EshA) showed extensive similarity to proteins from mycobacteria
      and a cyanobacterium, Synechococcus, that are abundant during nutritional stress
      but whose functions are unknown. Uniquely among these proteins, EshA contains a
      cyclic nucleotide-binding domain, suggesting that the activity of EshA may be
      modulated by a cyclic nucleotide. The eshA gene was strongly expressed from a
      single transcription start site only during sporulation, and accumulation of the
      eshA transcript depended on a developmental gene, bldA. During submerged
      sporulation, a null mutant strain that produced no EshA could not extend
      sporogenic hyphae from new branch points but instead accelerated septation and
      spore maturation at the preexisting vegetative filaments. These results indicated
      that EshA is required for the growth of sporogenic hyphae and localization of
      septation and spore maturation but not for spore viability.

PMID- 11325928
TI  - Cloning and functional characterization of an NAD(+)-dependent DNA ligase from
      Staphylococcus aureus.
AB  - A Staphylococcus aureus mutant conditionally defective in DNA ligase was
      identified by isolation of complementing plasmid clones that encode the S. aureus
      ligA gene. Orthologues of the putative S. aureus NAD(+)-dependent DNA ligase
      could be identified in the genomes of Bacillus stearothermophilus and other gram
      positive bacteria and confirmed the presence of four conserved amino acid motifs,
      including motif I, KXDG with lysine 112, which is believed to be the proposed
      site of adenylation. DNA sequence comparison of the ligA genes from wild type and
      temperature-sensitive S. aureus strain NT64 identified a single base alteration
      that is predicted to result in the amino acid substitution E46G. The S. aureus
      ligA gene was cloned and overexpressed in Escherichia coli, and the enzyme was
      purified to near homogeneity. NAD(+)-dependent DNA ligase activity was
      demonstrated with the purified enzyme by measuring ligation of (32)P-labeled 30
      mer and 29-mer oligonucleotides annealed to a complementary strand of DNA.
      Limited proteolysis of purified S. aureus DNA ligase by thermolysin produced
      products with apparent molecular masses of 40, 22, and 21 kDa. The fragments were
      purified and characterized by N-terminal sequencing and mass analysis. The N
      terminal fragment (40 kDa) was found to be fully adenylated. A fragment from
      residues 1 to 315 was expressed as a His-tagged fusion in E. coli and purified
      for functional analysis. Following deadenylation with nicotinamide
      mononucleotide, the purified fragment could self-adenylate but lacked detectable
      DNA binding activity. The 21- and 22-kDa C-terminal fragments, which lacked the
      last 76 amino acids of the DNA ligase, had no adenylation activity or DNA binding
      activity. The intact 30-kDa C terminus of the S. aureus LigA protein expressed in
      E. coli did demonstrate DNA binding activity. These observations suggest that, as
      in the case with the NAD(+)-dependent DNA ligase from B. stearothermophilus, two
      independent functional domains exist in S. aureus DNA ligase, consisting of
      separate adenylation and DNA binding activities. They also demonstrate a role for
      the extreme C terminus of the ligase in DNA binding. As there is much evidence to
      suggest that DNA ligase is essential for bacterial survival, its discovery in the
      important human pathogen S. aureus indicates its potential as a broad-spectrum
      antibacterial target for the identification of novel antibiotics.

PMID- 11325929
TI  - Events during initiation of archaeal transcription: open complex formation and
      DNA-protein interactions.
AB  - Transcription in Archaea is initiated by association of a TATA box binding
      protein (TBP) with a TATA box. This interaction is stabilized by the binding of
      the transcription factor IIB (TFIIB) orthologue TFB. We show here that the RNA
      polymerase of the archaeon Methanococcus, in contrast to polymerase II, does not
      require hydrolysis of the beta-gamma bond of ATP for initiation of transcription
      and open complex formation on linearized DNA. Permanganate probing revealed that
      the archaeal open complex spanned at least the DNA region from -11 to -1 at a
      tRNA(Val) promoter. The Methanococcus TBP-TFB promoter complex protected the DNA
      region from -40 to -14 on the noncoding DNA strand and the DNA segment from -36
      to -17 on the coding DNA strand from DNase I digestion. This DNase I footprint
      was extended only to the downstream end by the addition of the RNA polymerase to
      position +17 on the noncoding strand and to position +13 on the coding DNA
      strand.

PMID- 11325930
TI  - Response of Bacillus subtilis to cerulenin and acquisition of resistance.
AB  - Cerulenin is a fungal mycotoxin that potently inhibits fatty acid synthesis by
      covalent modification of the active site thiol of the chain-elongation subtypes
      of beta-ketoacyl-acyl carrier protein (ACP) synthases. The Bacillus subtilis fabF
      (yjaY) gene (fabF(b)) encodes an enzyme that catalyzes the condensation of
      malonyl-ACP with acyl-ACP to extend the growing acyl chain by two carbons. There
      were two mechanisms by which B. subtilis adapted to exposure to this antibiotic.
      First, reporter gene analysis demonstrated that transcription of the operon
      containing the fabF gene increased eightfold in response to a cerulenin
      challenge. This response was selective for the inhibition of fatty acid
      synthesis, since triclosan, an inhibitor of enoyl-ACP reductase, triggered an
      increase in fabF reporter gene expression while nalidixic acid did not. Second,
      spontaneous mutants arose that exhibited a 10-fold increase in the MIC of
      cerulenin. The mutation mapped at the B. subtilis fabF locus, and sequence
      analysis of the mutant fabF allele showed that a single base change resulted in
      the synthesis of FabF(b)[I108F]. The purified FabF(b) and FabF(b)[I108F] proteins
      had similar specific activities with myristoyl-ACP as the substrate. FabF(b)
      exhibited a 50% inhibitory concentration (IC(50)) of cerulenin of 0.1 microM,
      whereas the IC(50) for FabF(b)[I108] was 50-fold higher (5 microM). These
      biochemical data explain the absence of an overt growth defect coupled with the
      cerulenin resistance phenotype of the mutant strain.

PMID- 11325931
TI  - SpoVID guides SafA to the spore coat in Bacillus subtilis.
AB  - Bacteria assemble complex structures by targeting proteins to specific
      subcellular locations. The protein coat that encases Bacillus subtilis spores is
      an example of a structure that requires coordinated targeting and assembly of
      more than 24 polypeptides. The earliest stages of coat assembly require the
      action of three morphogenetic proteins: SpoIVA, CotE, and SpoVID. In the first
      steps, a basement layer of SpoIVA forms around the surface of the forespore,
      guiding the subsequent positioning of a ring of CotE protein about 75 nm from the
      forespore surface. SpoVID localizes near the forespore membrane where it
      functions to maintain the integrity of the CotE ring and to anchor the nascent
      coat to the underlying spore structures. However, it is not known which spore
      coat proteins interact directly with SpoVID. In this study we examined the
      interaction between SpoVID and another spore coat protein, SafA, in vivo using
      the yeast two-hybrid system and in vitro. We found evidence that SpoVID and SafA
      directly interact and that SafA interacts with itself. Immunofluorescence
      microscopy showed that SafA localized around the forespore early during coat
      assembly and that this localization of SafA was dependent on SpoVID. Moreover,
      targeting of SafA to the forespore was also dependent on SpoIVA, as was targeting
      of SpoVID to the forespore. We suggest that the localization of SafA to the spore
      coat requires direct interaction with SpoVID.

PMID- 11325932
TI  - Enzymatic removal of nitric oxide catalyzed by cytochrome c' in Rhodobacter
      capsulatus.
AB  - Cytochrome c' from Rhodobacter capsulatus has been shown to confer resistance to
      nitric oxide (NO). In this study, we demonstrated that the amount of cytochrome
      c' synthesized for buffering of NO is insufficient to account for the resistance
      to NO but that the cytochrome-dependent resistance mechanism involves the
      catalytic breakdown of NO, under aerobic and anaerobic conditions. Even under
      aerobic conditions, the NO removal is independent of molecular oxygen, suggesting
      cytochrome c' is a NO reductase. Indeed, we have measured the product of NO
      breakdown to be nitrous oxide (N(2)O), thus showing that cytochrome c' is
      behaving as a NO reductase. The increased resistance to NO conferred by
      cytochrome c' is distinct from the NO reductase pathway that is involved in
      denitrification. Cytochrome c' is not required for denitrification, but it has a
      role in the removal of externally supplied NO. Cytochrome c' synthesis occurs
      aerobically and anaerobically but is partly repressed under denitrifying growth
      conditions when other NO removal systems are operative. The inhibition of
      respiratory oxidase activity of R. capsulatus by NO suggests that one role for
      cytochrome c' is to maintain oxidase activity when both NO and O(2) are present.

PMID- 11325933
TI  - Contributions of PBP 5 and DD-carboxypeptidase penicillin binding proteins to
      maintenance of cell shape in Escherichia coli.
AB  - Escherichia coli has 12 recognized penicillin binding proteins (PBPs), four of
      which (PBPs 4, 5, and 6 and DacD) have DD-carboxypeptidase activity. Although the
      enzymology of the DD-carboxypeptidases has been studied extensively, the in vivo
      functions of these proteins are poorly understood. To explain why E. coli
      maintains four independent loci encoding enzymes of considerable sequence
      identity and comparable in vitro activity, it has been proposed that the DD
      carboxypeptidases may substitute for one another in vivo. We tested the validity
      of this equivalent substitution hypothesis by investigating the effects of these
      proteins on the aberrant morphology of DeltadacA mutants, which produce no PBP 5.
      Although cloned PBP 5 complemented the morphological phenotype of a DeltadacA
      mutant lacking a total of seven PBPs, controlled expression of PBP 4, PBP 6, or
      DacD did not. Also, a truncated PBP 5 protein lacking its amphipathic C-terminal
      membrane binding sequence did not reverse the morphological defects and was
      lethal at low levels of expression, implying that membrane anchoring is essential
      for the proper functioning of PBP 5. By examining a set of mutants from which
      multiple PBP genes were deleted, we found that significant morphological
      aberrations required the absence of at least three different PBPs. The greatest
      defects were observed in cells lacking, at minimum, PBPs 5 and 6 and one of the
      endopeptidases (either PBP 4 or PBP 7). The results further differentiate the
      roles of the low-molecular-weight PBPs, suggest a functional significance for the
      amphipathic membrane anchor of PBP 5 and, when combined with the recently
      determined crystal structure of PBP 5, suggest possible mechanisms by which these
      PBPs may contribute to maintenance of a uniform cell shape in E. coli.

PMID- 11325934
TI  - The CcrM DNA methyltransferase of Agrobacterium tumefaciens is essential, and its
      activity is cell cycle regulated.
AB  - DNA methylation is now recognized as a regulator of multiple bacterial cellular
      processes. CcrM is a DNA adenine methyltransferase found in the alpha subdivision
      of the proteobacteria. Like the Dam enzyme, which is found primarily in
      Escherichia coli and other gamma proteobacteria, it does not appear to be part of
      a DNA restriction-modification system. The CcrM homolog of Agrobacterium
      tumefaciens was found to be essential for viability. Overexpression of CcrM is
      associated with significant abnormalities of cell morphology and DNA ploidy.
      Mapping of the transcriptional start site revealed a conserved binding motif for
      the global response regulator CtrA at the -35 position; this motif was
      footprinted by purified Caulobacter crescentus CtrA protein in its phosphorylated
      state. We have succeeded in isolating synchronized populations of Agrobacterium
      cells and analyzing their progression through the cell cycle. We demonstrate that
      DNA replication and cell division can be followed in an orderly manner and that
      flagellin expression is cyclic, consistent with our observation that motility
      varies during the cell cycle. Using these synchronized populations, we show that
      CcrM methylation of the chromosome is restricted to the late S phase of the cell
      cycle. Thus, within the alpha subdivision, there is a conserved cell cycle
      dependence and regulatory mechanism controlling ccrM expression.

PMID- 11325935
TI  - Role of Escherichia coli nitrogen regulatory genes in the nitrogen response of
      the Azotobacter vinelandii NifL-NifA complex.
AB  - The redox-sensing flavoprotein NifL inhibits the activity of the nitrogen
      fixation (nif)-specific transcriptional activator NifA in Azotobacter vinelandii
      in response to molecular oxygen and fixed nitrogen. Although the mechanism
      whereby the A. vinelandii NifL-NifA system responds to fixed nitrogen in vivo is
      unknown, the glnK gene, which encodes a PII-like signal transduction protein, has
      been implicated in nitrogen control. However, the precise function of A.
      vinelandii glnK in this response is difficult to establish because of the
      essential nature of this gene. We have shown previously that A. vinelandii NifL
      is able to respond to fixed nitrogen to control NifA activity when expressed in
      Escherichia coli. In this study, we investigated the role of the E. coli PII-like
      signal transduction proteins in nitrogen control of the A. vinelandii NifL-NifA
      regulatory system in vivo. In contrast to recent findings with Klebsiella
      pneumoniae NifL, our results indicate that neither the E. coli PII nor GlnK
      protein is required to relieve inhibition by A. vinelandii NifL under nitrogen
      limiting conditions. Moreover, disruption of both the E. coli glnB and ntrC genes
      resulted in a complete loss of nitrogen regulation of NifA activity by NifL. We
      observe that glnB ntrC and glnB glnK ntrC mutant strains accumulate high levels
      of intracellular 2-oxoglutarate under conditions of nitrogen excess. These
      findings are in accord with our recent in vitro observations (R. Little, F. Reyes
      Ramirez, Y. Zhang, W. Van Heeswijk, and R. Dixon, EMBO J. 19:6041-6050, 2000) and
      suggest a model in which nitrogen control of the A. vinelandii NifL-NifA system
      is achieved through the response to the level of 2-oxoglutarate and an
      interaction with PII-like proteins under conditions of nitrogen excess.

PMID- 11325937
TI  - Aspartic peptide hydrolases in Salmonella enterica serovar typhimurium.
AB  - Two well-characterized enzymes in Salmonella enterica serovar Typhimurium and
      Escherichia coli are able to hydrolyze N-terminal aspartyl (Asp) dipeptides:
      peptidase B, a broad-specificity aminopeptidase, and peptidase E, an Asp-specific
      dipeptidase. A serovar Typhimurium strain lacking both of these enzymes, however,
      can still utilize most N-terminal Asp dipeptides as sources of amino acids, and
      extracts of such a strain contain additional enzymatic activities able to
      hydrolyze Asp dipeptides. Here we report two such activities from extracts of
      pepB pepE mutant strains of serovar Typhimurium identified by their ability to
      hydrolyze Asp-Leu. Although each of these activities hydrolyzes Asp-Leu at a
      measurable rate, the preferred substrates for both are N-terminal isoAsp
      peptides. One of the activities is a previously characterized isoAsp dipeptidase
      from E. coli, the product of the iadA gene. The other is the product of the
      serovar Typhimurium homolog of E. coli ybiK, a gene of previously unknown
      function. This gene product is a member of the N-terminal nucleophile structural
      family of amidohydrolases. Like most other members of this family, the mature
      enzyme is generated from a precursor protein by proteolytic cleavage and the
      active enzyme is a heterotetramer. Based on its ability to hydrolyze an N
      terminal isoAsp tripeptide as well as isoAsp dipeptides, the enzyme appears to be
      an isoAsp aminopeptidase, and we propose that the gene encoding it be designated
      iaaA (isoAsp aminopeptidase). A strain lacking both IadA and IaaA in addition to
      peptidase B and peptidase E has been constructed. This strain utilizes Asp-Leu as
      a leucine source, and extracts of this strain contain at least one additional, as
      yet-uncharacterized, peptidase able to cleave Asp dipeptides.

PMID- 11325936
TI  - Glucose-induced monoubiquitination of the Saccharomyces cerevisiae galactose
      transporter is sufficient to signal its internalization.
AB  - In Saccharomyces cerevisiae, the addition of glucose to cells growing on
      galactose induces internalization of the galactose transporter Gal2p and its
      subsequent proteolysis in the vacuole. Here we report that the essential step in
      Gal2p down-regulation is its ubiquitination through the Ubc1p-Ubc4p-Ubc5p triad
      of ubiquitin-conjugating enzymes and Npi1/Rsp5p ubiquitin-protein ligase.
      Moreover, Gal2p appears to be stabilized in mutant cells defective in the
      ubiquitin-hydrolase Npi2p/Doa4p, and the mutant phenotype can be reversed by
      overexpression of ubiquitin. An analysis of the fate of Gal2p in cells
      overexpressing wild-type ubiquitin as well as its variants incompetent to form
      polyubiquitin chains showed that monoubiquitination of Gal2p is sufficient to
      signal internalization of the protein into the endocytic pathway.

PMID- 11325938
TI  - Tagging morphogenetic genes by insertional mutagenesis in the yeast Yarrowia
      lipolytica.
AB  - The yeast Yarrowia lipolytica is distantly related to Saccharomyces cerevisiae,
      can be genetically modified, and can grow in both haploid and diploid states in
      either yeast, pseudomycelial, or mycelial forms, depending on environmental
      conditions. Previous results have indicated that the STE and RIM pathways, which
      mediate cellular switching in other dimorphic yeasts, are not required for Y.
      lipolytica morphogenesis. To identify the pathways involved in morphogenesis, we
      mutagenized a wild-type strain of Y. lipolytica with a Tn3 derivative. We
      isolated eight tagged mutants, entirely defective in hyphal formation, from a
      total of 40,000 mutants and identified seven genes homologous to S. cerevisiae
      CDC25, RAS2, BUD6, KEX2, GPI7, SNF5, and PPH21. We analyzed their abilities to
      invade agar and to form pseudomycelium or hyphae under inducing conditions and
      their sensitivity to temperature and to Calcofluor white. Chitin staining was
      used to detect defects in their cell walls. Our results indicate that a
      functional Ras-cyclic AMP pathway is required for the formation of hyphae in Y.
      lipolytica and that perturbations in the processing of extracellular, possibly
      parietal, proteins result in morphogenetic defects.

PMID- 11325939
TI  - The autolytic enzyme LytA of Streptococcus pneumoniae is not responsible for
      releasing pneumolysin.
AB  - It was previously proposed that autolysin's primary role in the virulence of
      pneumococci was to release pneumolysin to an extracellular location. This
      interpretation came into question when pneumolysin was observed to be released in
      significant amounts from some pneumococci during log-phase growth, because
      autolysis was not believed to occur at this time. We have reexamined this
      phenomenon in detail for one such strain, WU2. This study found that the
      extracellular release of pneumolysin from WU2 was not dependent on autolysin
      action. A mutant lacking autolysin showed the same pattern of pneumolysin release
      as the wild-type strain. Addition of mitomycin C to a growing WU2 culture did not
      induce lysis, indicating the absence of resident bacteriophages that could
      potentially harbor lytA-like genes. Furthermore, release of pneumolysin was
      unaltered by growth in 2% choline, a condition which is reported to inactivate
      autolysin, as well as most known pneumococcal phage lysins. Profiles of total
      proteins in the cytoplasm and in the supernatant media supported the hypothesis
      that release of pneumolysin is independent of pneumococcal lysis. Finally, under
      some infection conditions, mutations in pneumolysin and autolysin had different
      effects on virulence.

PMID- 11325940
TI  - A Phosphopantetheinyl transferase homolog is essential for Photorhabdus
      luminescens to support growth and reproduction of the entomopathogenic nematode
      Heterorhabditis bacteriophora.
AB  - The bacterium Photorhabdus luminescens is a symbiont of the entomopathogenic
      nematode Heterorhabditis bacteriophora. The nematode requires the bacterium for
      infection of insect larvae and as a substrate for growth and reproduction. The
      nematodes do not grow and reproduce in insect hosts or on artificial media in the
      absence of viable P. luminescens cells. In an effort to identify bacterial
      factors that are required for nematode growth and reproduction, transposon
      induced mutants of P. luminescens were screened for the loss of the ability to
      support growth and reproduction of H. bacteriophora nematodes. One mutant,
      NGR209, consistently failed to support nematode growth and reproduction. This
      mutant was also defective in the production of siderophore and antibiotic
      activities. The transposon was inserted into an open reading frame homologous to
      Escherichia coli EntD, a 4'-phosphopantetheinyl (Ppant) transferase, which is
      required for the biosynthesis of the catechol siderophore enterobactin. Ppant
      transferases catalyze the transfer of the Ppant moiety from coenzyme A to a holo
      acyl, -aryl, or -peptidyl carrier protein(s) required for the biosynthesis of
      fatty acids, polyketides, or nonribosomal peptides. Possible roles of a Ppant
      transferase in the ability of P. luminescens to support nematode growth and
      reproduction are discussed.

PMID- 11325941
TI  - Osmoregulated periplasmic glucans of Erwinia chrysanthemi.
AB  - We report the initial characterization of the osmoregulated periplasmic glucans
      (OPGs) of Erwinia chrysanthemi. OPGs are intrinsic components of the bacterial
      envelope necessary to the pathogenicity of this phytopathogenic enterobacterium
      (F. Page, S. Altabe, N. Hugouvieux-Cotte-Pattat, J.-M. Lacroix, J. Robert-Baudouy
      and J.-P. Bohin, J. Bacteriol. 183:0000-0000, 2001 [companion in this issue]).
      OPGs were isolated by trichloracetic acid treatment and gel permeation
      chromatography. The synthesis of these compounds appeared to be osmoregulated,
      since lower amounts of OPGs were produced when bacteria were grown in media of
      higher osmolarities. However, a large fraction of these OPGs were recovered in
      the culture medium. Then, these compounds were characterized by compositional
      analysis, high-performance anion-exchange chromatography, matrix-assisted laser
      desorption mass spectrometry, and (1)H and (13)C nuclear magnetic resonance
      analyses. OPGs produced by E. chrysanthemi are very heterogeneous at the level of
      both backbone structure and substitution of these structures. The degree of
      polymerization of the glucose units ranges from 5 to 12. The structures are
      branched, with a linear backbone consisting of beta-1,2-linked glucose units to
      which a variable number of branches, composed of one glucose residue, are
      attached by beta-1,6 linkages in a random way. This glucan backbone may be
      substituted by O-acetyl and O-succinyl ester-linked residues.

PMID- 11325942
TI  - Osmoregulated periplasmic glucan synthesis is required for Erwinia chrysanthemi
      pathogenicity.
AB  - Erwinia chrysanthemi is a phytopathogenic enterobacterium causing soft rot
      disease in a wide range of plants. Osmoregulated periplasmic glucans (OPGs) are
      intrinsic components of the gram-negative bacterial envelope. We cloned the opgGH
      operon of E. chrysanthemi, encoding proteins involved in the glucose backbone
      synthesis of OPGs, by complementation of the homologous locus mdoGH of
      Escherichia coli. OpgG and OpgH show a high level of similarity with MdoG and
      MdoH, respectively, and mutations in the opgG or opgH gene abolish OPG synthesis.
      The opg mutants exhibit a pleiotropic phenotype, including overproduction of
      exopolysaccharides, reduced motility, bile salt hypersensitivity, reduced
      protease, cellulase, and pectate lyase production, and complete loss of
      virulence. Coinoculation experiments support the conclusion that OPGs present in
      the periplasmic space of the bacteria are necessary for growth in the plant host.

PMID- 11325943
TI  - The N terminus of FliM is essential to promote flagellar rotation in Rhodobacter
      sphaeroides.
AB  - FliM is part of the flagellar switch complex. Interaction of this protein with
      phospho-CheY (CheY-P) through its N terminus constitutes the main information
      relay point between the chemotactic system and the flagellum. In this work, we
      evaluated the role of the N terminus of FliM in the swimming behavior of
      Rhodobacter sphaeroides. Strains expressing the FliM protein with substitutions
      in residues previously reported in Escherichia coli as being important for
      interaction with CheY showed an increased stop frequency compared with wild-type
      cells. In accordance, we observed that R. sphaeroides cells expressing FliM
      lacking either the first 13 or 20 amino acids from the N terminus showed a
      stopped phenotype. We show evidence that FliMDelta13 and FliMDelta20 are stable
      proteins and that cells expressing them allow flagellin export at levels
      indistinguishable from those detected for the wild-type strain. These results
      suggest that the N-terminal region of FliM is required to promote swimming in
      this bacterium. The role of CheY in controlling flagellar rotation in this
      organism is discussed.

PMID- 11325944
TI  - The phosphoryl transfer domain of UhpB interacts with the response regulator
      UhpA.
AB  - Bacterial two-component regulatory systems control the expression of target genes
      through regulated changes in protein phosphorylation. Signal reception alters the
      ability of a membrane-bound histidine kinase (HK) protein to transfer phosphate
      from ATP to a highly conserved histidine residue. The transfer of phosphate from
      the histidine to an aspartate residue on the cognate response regulator (RR)
      changes the ability of the latter protein to bind to target DNA sequences and to
      alter gene transcription. UhpB is the HK protein which controls production of the
      sugar phosphate transporter UhpT. Elevated expression of full-length UhpB or of a
      soluble hybrid protein, GST-Bc, which is glutathione S-transferase (GST) fused to
      the cytoplasmic C-terminal portion of UhpB, results in complete blockage of uhpT
      expression in a uhp(+) strain. This dominant-negative interference could result
      from the ability of GST-Bc to bind and sequester the RR UhpA and to accelerate
      its dephosphorylation. The portion of GST-Bc responsible for the interference
      phenotype was localized using truncation, linker insertion, and point mutations
      to the region between residues 293 and 366 flanking His-313, the putative site of
      autophosphorylation. Point mutations which allow GST-Bc to activate uhpT
      expression or which relieve the interference phenotype were obtained at numerous
      sites throughout this region. This region of UhpB is related to the phosphoryl
      transfer domain of EnvZ, which forms half of an interdimer four-helix bundle and
      is responsible for dimerization of its cytoplasmic domain. The expression of GST
      fusion proteins carrying the corresponding portions of EnvZ strongly interfered
      with the activation of porin gene expression by OmpR. The GST-Bc protein
      accelerated dephosphorylation of P-UhpA. Reverse transfer of phosphate from P
      UhpA to GST-Bc was observed in the presence of the metal chelator EDTA and
      depended on the presence of His-313. Phosphate transfer from P-UhpA to the
      liberated phosphoryl transfer domain also occurred. Taken together, these results
      indicate that the phosphoryl transfer-dimerization domain of UhpB participates in
      the specific binding of UhpA, in the control of autokinase activity, and in the
      dephosphorylation of P-UhpA.

PMID- 11325945
TI  - ComE, a competence protein from Neisseria gonorrhoeae with DNA-binding activity.
AB  - Neisseria gonorrhoeae is naturally able to take up exogenous DNA and undergo
      genetic transformation. This ability correlates with the presence of functional
      type IV pili, and uptake of DNA is dependent on the presence of a specific 10-bp
      sequence. Among the known competence factors in N. gonorrhoeae, none has been
      shown to interact with the incoming DNA. Here we describe ComE, a DNA-binding
      protein involved in neisserial competence. The gene comE was identified through
      similarity searches in the gonococcal genome sequence, using as the query ComEA,
      the DNA receptor in competent Bacillus subtilis. The gene comE is present in four
      identical copies in the genomes of both N. gonorrhoeae and Neisseria
      meningitidis, located downstream of each of the rRNA operons. Single-copy
      deletion of comE in N. gonorrhoeae did not have a measurable effect on
      competence, whereas serial deletions led to gradual decrease in transformation
      frequencies, reaching a 4 x 10(4)-fold reduction when all copies were deleted.
      Transformation deficiency correlated with impaired ability to take up exogenous
      DNA; however, the mutants presented normal piliation and twitching motility
      phenotype. The product of comE has 99 amino acids, with a predicted signal
      peptide; by immunodetection, a 8-kDa protein corresponding to processed ComE was
      observed in different strains of N. gonorrhoeae and N. meningitidis. Recombinant
      His-tagged ComE showed DNA binding activity, without any detectable sequence
      specificity. Thus, we identified a novel gonococcal DNA-binding competence factor
      which is necessary for DNA uptake and does not affect pilus biogenesis or
      function.

PMID- 11325946
TI  - Promoter cloning in the radioresistant bacterium Deinococcus radiodurans.
AB  - Deinococcus radiodurans is a highly radiation-resistant bacterium that is classed
      in a major subbranch of the bacterial domain. Since very little is known about
      gene expression in this bacterium, an initial study of promoters was undertaken.
      In order to isolate promoters and study promoter function, a series of
      integrative vectors for stable chromosomal insertion in D. radiodurans were
      developed. These vectors are based on Escherichia coli replicons that are unable
      to replicate autonomously in D. radiodurans and carry homologous sequences for
      replacement recombination in the D. radiodurans chromosome. The resulting
      integration vectors were used to study expression of reporter genes fused to a
      number of putative promoters that were amplified from the D. radiodurans R1
      genome. Further analysis of these and other putative promoters was performed by
      Northern hybridization and primer extension experiments. In contrast to previous
      reports, the -10 and -35 regions of these promoters resembled the sigma(70)
      consensus sequence of E. coli.

PMID- 11325947
TI  - Functional and mutational analysis of p19, a DNA transfer protein with muramidase
      activity.
AB  - Protein P19 encoded by the conjugative resistance plasmid R1 has been identified
      as being one member of a large family of muramidases encoded by bacteriophages
      and by type III and type IV secretion systems. We carried out a mutational
      analysis to investigate the function of protein P19 and used in vivo
      complementation assays to test those of several P19 mutants. The results
      indicated that conserved residues present in the presumed catalytic center of P19
      are absolutely essential for its function in conjugation of plasmid R1 and
      infection by the RNA phage R17. Overexpression of protein P19 in an early growth
      phase resulted in a massive lysis of Escherichia coli cells in liquid culture, as
      indicated by a rapid and distinct decrease in cell culture densities after
      induction. Change of the proposed catalytic glutamate at position 44 to glutamine
      completely abolished this effect. P19-induced cell lysis was directly shown by
      transmission and scanning electron microscopy. Typically, P19-overexpressing
      cells showed bulges protruding from the cell surfaces. Our interpretation is that
      these protrusions arose from a localized and spatially confined disruption of the
      bacterial cell wall. To our knowledge such an effect has not previously been
      documented for any member of the lytic transglycosylase family. From the data
      presented here, we conclude that protein P19 possesses the proposed localized
      peptidoglycan-hydrolyzing activity. This activity would be a prerequisite for
      efficient penetration of the cell envelope by the DNA translocation complex
      encoded by the conjugative plasmid.

PMID- 11325948
TI  - Role of acid metabolism in Streptomyces coelicolor morphological differentiation
      and antibiotic biosynthesis.
AB  - Studies of citrate synthase (CitA) were carried out to investigate its role in
      morphological development and biosynthesis of antibiotics in Streptomyces
      coelicolor. Purification of CitA, the major vegetative enzyme activity, allowed
      characterization of its kinetic properties. The apparent K(m) values of CitA for
      acetyl coenzyme A (acetyl-CoA) (32 microM) and oxaloacetate (17 microM) were
      similar to those of citrate synthases from other gram-positive bacteria and
      eukaryotes. CitA was not strongly inhibited by various allosteric feedback
      inhibitors (NAD(+), NADH, ATP, ADP, isocitrate, or alpha-ketoglutarate). The
      corresponding gene (citA) was cloned and sequenced, allowing construction of a
      citA mutant (BZ2). BZ2 was a glutamate auxotroph, indicating that citA encoded
      the major citrate synthase allowing flow of acetyl-CoA into the tricarboxylic
      acid (TCA) cycle. Interruption of aerobic TCA cycle-based metabolism resulted in
      acidification of the medium and defects in morphological differentiation and
      antibiotic biosynthesis. These developmental defects of the citA mutant were in
      part due to a glucose-dependent medium acidification that was also exhibited by
      some other bald mutants. Unlike other acidogenic bald strains, citA and bldJ
      mutants were able to produce aerial mycelia and pigments when the medium was
      buffered sufficiently to maintain neutrality. Extracellular complementation
      studies suggested that citA defines a new stage of the Streptomyces developmental
      cascade.

PMID- 11325949
TI  - Roles of aconitase in growth, metabolism, and morphological differentiation of
      Streptomyces coelicolor.
AB  - The studies of aconitase presented here, along with those of citrate synthase (P.
      H. Viollier, W. Minas, G. E. Dale, M. Folcher, and C. J. Thompson, J. Bacteriol.
      183:3184-3192, 2001), were undertaken to investigate the role of the
      tricarboxylic acid (TCA) cycle in Streptomyces coelicolor development. A single
      aconitase activity (AcoA) was detected in protein extracts of cultures during
      column purification. The deduced amino acid sequence of the cloned acoA gene
      constituted the N-terminal sequence of semipurified AcoA and was homologous to
      bacterial A-type aconitases and bifunctional eukaryotic aconitases (iron
      regulatory proteins). The fact that an acoA disruption mutant (BZ4) did not grow
      on minimal glucose media in the absence of glutamate confirmed that this gene
      encoded the primary vegetative aconitase catalyzing flux through the TCA cycle.
      On glucose-based complete medium, BZ4 had defects in growth, antibiotic
      biosynthesis, and aerial hypha formation, partially due to medium acidification
      and accumulation of citrate. The inhibitory effects of acids and citrate on BZ4
      were partly suppressed by buffer or by introducing a citrate synthase mutation.
      However, the fact that growth of an acoA citA mutant remained impaired, even on a
      nonacidogenic carbon source, suggested alternative functions of AcoA. Immunoblots
      revealed that AcoA was present primarily during substrate mycelial growth on
      solid medium. Transcription of acoA was limited to the early growth phase in
      liquid cultures from a start site mapped in vitro and in vivo.

PMID- 11325950
TI  - A homolog of the CtrA cell cycle regulator is present and essential in
      Sinorhizobium meliloti.
AB  - During development of the symbiotic soil bacterium Sinorhizobium meliloti into
      nitrogen-fixing bacteroids, DNA replication and cell division cease and the cells
      undergo profound metabolic and morphological changes. Regulatory genes
      controlling the early stages of this process have not been identified. As a first
      step in the search for regulators of these events, we report the isolation and
      characterization of a ctrA gene from S. meliloti. We show that the S. meliloti
      CtrA belongs to the CtrA-like family of response regulators found in several
      alpha-proteobacteria. In Caulobacter crescentus, CtrA is essential and is a
      global regulator of multiple cell cycle functions. ctrA is also an essential gene
      in S. meliloti, and it is expressed similarly to the autoregulated C. crescentus
      ctrA in that both genes have complex promoter regions which bind phosphorylated
      CtrA.

PMID- 11325951
TI  - CAP1, an adenylate cyclase-associated protein gene, regulates bud-hypha
      transitions, filamentous growth, and cyclic AMP levels and is required for
      virulence of Candida albicans.
AB  - In response to a wide variety of environmental stimuli, the opportunistic fungal
      pathogen Candida albicans exits the budding cycle, producing germ tubes and
      hyphae concomitant with expression of virulence genes, such as that encoding
      hyphal wall protein 1 (HWP1). Biochemical studies implicate cyclic AMP (cAMP)
      increases in promoting bud-hypha transitions, but genetic evidence relating genes
      that control cAMP levels to bud-hypha transitions has not been reported.
      Adenylate cyclase-associated proteins (CAPs) of nonpathogenic fungi interact with
      Ras and adenylate cyclase to increase cAMP levels under specific environmental
      conditions. To initiate studies on the relationship between cAMP signaling and
      bud-hypha transitions in C. albicans, we identified, cloned, characterized, and
      disrupted the C. albicans CAP1 gene. C. albicans strains with inactivated CAP1
      budded in conditions that led to germ tube formation in isogenic strains with
      CAP1. The addition of 10 mM cAMP and dibutyryl cAMP promoted bud-hypha
      transitions and filamentous growth in the cap1/cap1 mutant in liquid and solid
      media, respectively, showing clearly that cAMP promotes hypha formation in C.
      albicans. Increases in cytoplasmic cAMP preceding germ tube emergence in strains
      having CAP1 were markedly diminished in the budding cap1/cap1 mutant. C. albicans
      strains with deletions of both alleles of CAP1 were avirulent in a mouse model of
      systemic candidiasis. The avirulence of a germ tube-deficient cap1/cap1 mutant
      coupled with the role of Cap1 in regulating cAMP levels shows that the Cap1
      mediated cAMP signaling pathway is required for bud-hypha transitions,
      filamentous growth, and the pathogenesis of candidiasis.

PMID- 11325952
TI  - Genes involved in control of galactose uptake in Lactobacillus brevis and
      reconstitution of the regulatory system in Bacillus subtilis.
AB  - The heterofermentative lactic acid bacterium Lactobacillus brevis transports
      galactose and the nonmetabolizable galactose analogue thiomethyl-beta-galactoside
      (TMG) by a permease-catalyzed sugar:H(+) symport mechanism. Addition of glucose
      to L. brevis cells loaded with [(14)C]TMG promotes efflux and prevents
      accumulation of the galactoside, probably by converting the proton symporter into
      a uniporter. Such a process manifests itself physiologically in phenomena termed
      inducer expulsion and exclusion. Previous evidence suggested a direct allosteric
      mechanism whereby the phosphocarrier protein, HPr, phosphorylated at serine-46
      [HPr(Ser-P)], binds to the galactose:H(+) symporter to uncouple sugar transport
      from proton symport. To elucidate the molecular mechanism of inducer control in
      L. brevis, we have cloned the genes encoding the HPr(Ser) kinase, HPr, enzyme I,
      and the galactose:H(+) symporter. The sequences of these genes were determined,
      and the relevant phylogenetic trees are presented. Mutant HPr derivatives in
      which the regulatory serine was changed to either alanine or aspartate were
      constructed. The cloned galP gene was integrated into the chromosome of Bacillus
      subtilis, and synthesis of the mutant HPr proteins in this organism was shown to
      promote regulation of GalP, as expected for a direct allosteric mechanism. We
      have thus reconstituted inducer control in an organism that does not otherwise
      exhibit this phenomenon. These results are consistent with the conclusion that
      inducer exclusion and expulsion in L. brevis operates via a multicomponent signal
      transduction mechanism wherein the presence of glycolytic intermediates such as
      fructose 1,6-bisphosphate (the intracellular effector), derived from exogenous
      glucose (the extracellular effector), activates HPr(Ser) kinase (the sensor) to
      phosphorylate HPr on Ser-46 (the messenger), which binds to the galactose:H(+)
      symporter (the target), resulting in uncoupling of sugar transport from proton
      symport (the response). This cascade allows bacteria to quickly respond to
      changes in external sugar concentrations. Understanding the molecular mechanism
      of inducer control advances our knowledge of the link between metabolic and
      transport processes in bacteria.

PMID- 11325953
TI  - Two ResD-controlled promoters regulate ctaA expression in Bacillus subtilis.
AB  - The Bacillus subtilis ResDE two-component system plays a positive role in global
      regulation of genes involved in aerobic and anaerobic respiration. ctaA is one of
      the several genes involved in aerobic respiration that requires ResD for in vivo
      expression. The ctaAB-divergent promoter regulatory region has three ResD binding
      sites; A1, A2, and A3. The A2 site is essential for in vivo promoter activity,
      while binding sites A2 and A3 are required for full ctaA promoter activity. In
      this study, we demonstrate the role of ResD~P in the activation of the ctaA
      promoter using an in vitro transcription system. The results indicate that the
      ctaA promoter (binding sites A2 and A3) has two transcriptional start sites.
      Binding site A2 was sufficient for weak transcription of the upstream promoter
      (Pv) by Esigma(A), transcription which was enhanced approximately 1.5-fold by
      ResD and 5-fold by ResD~P. The downstream promoter (Ps) required both binding
      sites A2 and A3 and was not transcribed by Esigma(A) with or without ResD~P. RNA
      polymerase (RNAP) isolated from B. subtilis when cells were at the end of
      exponential growth (T(0)) or 3, 4, or 5 h into the stationary phase (T(3), T(4),
      or T( 5), respectively) was used in in vitro transcription assays. Maximal
      transcription from Ps required T(4) RNAP plus ResD~P. RNAP isolated from a spo0A
      or a sigE mutant strain was not capable of Ps transcription. Comparison of the Ps
      promoter sequence with the SigE binding consensus suggests that the ctaA Ps
      promoter may be a SigE promoter. The collective data from ResD footprinting, in
      vivo promoter deletion analysis, and in vitro transcription assays suggest that
      ctaA is transcribed during late exponential to early stationary phases of growth
      from the Pv promoter, which requires ResD binding site A2, Esigma(A), and ResD~P,
      and during later stationary phase from Ps, which requires binding sites A2 and
      A3, ResD~P, and Esigma(E) or a sigma factor whose transcription is dependent on
      SigE.

PMID- 11325954
TI  - Functional complementation of pyran ring formation in actinorhodin biosynthesis
      in Streptomyces coelicolor A3(2) by ketoreductase genes for granaticin
      biosynthesis.
AB  - A mutation in actVI-ORF1, which controls C-3 reduction in actinorhodin
      biosynthesis by Streptomyces coelicolor, was complemented by gra-ORF5 and -ORF6
      from the granaticin biosynthetic gene cluster of Streptomyces violaceoruber Tu22.
      It is hypothesized that, while gra-ORF5 alone is a ketoreductase for C-9, gra
      ORF6 gives the enzyme regiospecificity also for C-3.

PMID- 11325956
TI  - Effects of mutations in the Pseudomonas putida miaA gene: regulation of the trpE
      and trpGDC operons in P. putida by attenuation.
AB  - Tn5 insertion mutants defective in regulation of the Pseudomonas putida trpE and
      trpGDC operons by tryptophan were found to contain insertions in the P. putida
      miaA gene, whose product (in Escherichia coli) modifies tRNA(Trp) and is required
      for attenuation. Nucleotide sequences upstream of trpE and trpG encode putative
      leader peptides similar in sequence to leader peptides found in other bacterial
      species, and the phenotypes of the mutants strongly suggest that transcription of
      these operons is regulated solely by attenuation.

PMID- 11325957
TI  - Persistent activation of NF-kappa B by the tax transforming protein involves
      chronic phosphorylation of IkappaB kinase subunits IKKbeta and IKKgamma.
AB  - The Tax transforming protein encoded by human T-cell leukemia virus type 1
      (HTLV1) persistently activates transcription factor NF-kappaB and deregulates the
      expression of downstream genes that mediate cell cycle entry. We recently found
      that Tax binds to and chronically stimulates the catalytic function of IkappaB
      kinase (IKK), a cellular enzyme complex that phosphorylates and inactivates the
      IkappaB inhibitory subunit of NF-kappaB. We now demonstrate that the IKKbeta
      catalytic subunit and IKKgamma regulatory subunit of IKK are chronically
      phosphorylated in HTLV1-infected and Tax-transfected cells. Alanine substitutions
      at Ser-177 and Ser-181 in the T loop of IKKbeta protect both of these IKK
      subunits from Tax-directed phosphorylation and prevent the induction of IkappaB
      kinase activity. Each of these inhibitory effects is recapitulated in Tax
      transfectants expressing the bacterial protein YopJ, a potent in vivo agonist of
      T loop phosphorylation. Moreover, ectopically expressed forms of IKKbeta that
      contain glutamic acid substitutions at Ser-177 and Ser-181 have the capacity to
      phosphorylate a recombinant IKKgamma substrate in vitro. We conclude that Tax
      induced phosphorylation of IKKbeta is required for IKKbeta activation, phosphoryl
      group transfer to IKKgamma, and acquisition of the deregulated IKK phenotype.

PMID- 11325955
TI  - Cloning and expression of two genes coding for sodium pumps in the salt-tolerant
      yeast Debaryomyces hansenii.
AB  - Two genes encoding Na(+)-ATPases from Debaryomyces hansenii were cloned and
      sequenced. The genes, designated ENA1 from D. hansenii (DhENA1) and DhENA2,
      exhibited high homology with the corresponding genes from Schwanniomyces
      occidentalis. DhENA1 was expressed in the presence of high Na(+) concentrations,
      while the expression of DhENA2 also required high pH. A mutant of Saccharomyces
      cerevisiae lacking the Na(+) efflux systems and sensitive to Na(+), when
      transformed with DhENA1 or DhENA2, recovered Na(+) tolerance and also the ability
      to extrude Na(+).

PMID- 11325958
TI  - Characterization of an N-system amino acid transporter expressed in retina and
      its involvement in glutamine transport.
AB  - We report here on the characterization of a mouse N-system amino acid transporter
      protein, which is involved in the transport of glutamine. This protein of 485
      amino acids shares 52% sequence homology with an N-system amino acid transporter,
      mouse N-system amino acid transporter (mNAT) and its orthologs. Because this
      protein shares a high degree of sequence homology and functional similarity to
      mNAT, we named it mNAT2. mNAT2 is predominately expressed in the retina and to a
      slightly lesser extent in the brain. In the retina, it is located in the axons of
      ganglion cells in the nerve fiber layer and in the bundles of the optic nerve.
      Functional analysis of mNAT2 expressed in Xenopus oocytes revealed that the
      strongest transport activities were specific for l-glutamine. In addition, mNAT2
      is a Na(+)- and pH-dependent, high affinity transporter and partially tolerates
      substitution of Na(+) by Li(+). Additionally, mNAT2 functions as a carrier
      mediated transporter that facilitates efflux. The unique expression pattern and
      selective glutamine transport properties of mNAT2 suggest that it plays a
      specific role in the uptake of glutamine involved in the generation of the
      neurotransmitter glutamate in retina.

PMID- 11325959
TI  - The Bloom's syndrome protein (BLM) interacts with MLH1 but is not required for
      DNA mismatch repair.
AB  - Bloom's syndrome (BS) is a rare autosomal recessive disorder characterized by pre
      and postnatal growth deficiency, immunodeficiency, and a tremendous
      predisposition to a wide variety of cancers. Cells from BS individuals are
      characterized by a high incidence of chromosomal gaps and breaks, elevated sister
      chromatid exchange, quadriradial formations, and locus-specific mutations. BS is
      the consequence of mutations that lead to loss of function of BLM, a gene
      encoding a helicase with homology to the RecQ helicase family. To delineate the
      role of BLM in DNA replication, recombination, and repair we used a yeast two
      hybrid screen to identify potential protein partners of the BLM helicase. The C
      terminus of BLM interacts directly with MLH1 in the yeast-two hybrid assay; far
      Western analysis and co-immunoprecipitations confirmed the interaction. Cell
      extracts deficient in BLM were competent for DNA mismatch repair. These data
      suggest that the BLM helicase and MLH1 function together in replication,
      recombination, or DNA repair events independent of single base mismatch repair.

PMID- 11325960
TI  - Placental protein 14 induces apoptosis in T cells but not in monocytes.
AB  - Substantial evidence exists in literature to suggest that placental protein 14
      (PP14) (recently renamed glycodelin A), exhibits immunosuppressive properties and
      is an indispensable macromolecule in the maternal system for the establishment,
      maintenance, and progression of pregnancy. Though there are several reports
      substantiating the above, the mechanism of its action at the molecular level has
      not been elucidated as yet. In this paper we provide data that suggest that
      amniotic fluid PP14 and recombinant PP14 expressed in Pichia pastoris induce
      apoptosis in human peripheral blood lymphocytes upon activation, independent of
      monocytes. That PP14 has a direct apoptotic action on T cells but not on
      monocytes was also demonstrated by utilizing human cell lines. PP14 was shown to
      induce apoptosis in the human T cell lines, Jurkat and MOLT-4 cells, but not in
      the human monocytic cell line, U937.

PMID- 11325961
TI  - The mechanism of the remodeling of high density lipoproteins by phospholipid
      transfer protein.
AB  - Phospholipid transfer protein (PLTP) remodels high density lipoproteins (HDL)
      into large and small particles. It also mediates the dissociation of lipid-poor
      or lipid-free apolipoprotein A-I (apoA-I) from HDL. Remodeling is enhanced
      markedly in triglyceride (TG)-enriched HDL (Rye, K.-A., Jauhiainen, M., Barter,
      P. J., and Ehnholm. C. (1998) J. Lipid. Res. 39, 613-622). This study defines the
      mechanism of the remodeling of HDL by PLTP and determines why it is enhanced in
      TG-enriched HDL. Homogeneous populations of spherical reconstituted HDL (rHDL)
      containing apoA-I and either cholesteryl esters only (CE-rHDL; diameter 9.3 nm)
      or CE and TG in their core (TG-rHDL; diameter 9.5 nm) were used. After 24 h of
      incubation with PLTP, all of the TG-rHDL, but only a proportion of the CE-rHDL,
      were converted into large (11.3-nm diameter) and small (7.7-nm diameter)
      particles. Only small particles were formed during the first 6 h of incubation of
      CE-rHDL with PLTP. The large particles and dissociated apoA-I were apparent after
      12 h. In the case of TG-rHDL, small particles appeared after 1 h of incubation,
      while dissociated apoA-I and large particles were apparent at 3 h. The
      composition of the large particles indicated that they were derived from a fusion
      product. Spectroscopic studies indicated that the apoA-I in TG-rHDL was less
      stable than the apoA-I in CE-rHDL. In conclusion, these results show that (i)
      PLTP mediates rHDL fusion, (ii) the fusion product rearranges by two independent
      processes into small and large particles, and (iii) the more rapid remodeling of
      TG-rHDL by PLTP may be due to the destabilization of apoA-I.

PMID- 11325962
TI  - Cep-1347 (KT7515), a semisynthetic inhibitor of the mixed lineage kinase family.
AB  - CEP-1347 (KT7515) promotes neuronal survival at dosages that inhibit activation
      of the c-Jun amino-terminal kinases (JNKs) in primary embryonic cultures and
      differentiated PC12 cells after trophic withdrawal and in mice treated with 1
      methyl-4-phenyl tetrahydropyridine. In an effort to identify molecular target(s)
      of CEP-1347 in the JNK cascade, JNK1 and known upstream regulators of JNK1 were
      co-expressed in Cos-7 cells to determine whether CEP-1347 could modulate JNK1
      activation. CEP-1347 blocked JNK1 activation induced by members of the mixed
      lineage kinase (MLK) family (MLK3, MLK2, MLK1, dual leucine zipper kinase, and
      leucine zipper kinase). The response was selective because CEP-1347 did not
      inhibit JNK1 activation in cells induced by kinases independent of the MLK
      cascade. CEP-1347 inhibition of recombinant MLK members in vitro was competitive
      with ATP, resulting in IC(50) values ranging from 23 to 51 nm, comparable to
      inhibitory potencies observed in intact cells. In addition, overexpression of
      MLK3 led to death in Chinese hamster ovary cells, and CEP-1347 blocked this death
      at doses comparable to those that inhibited MLK3 kinase activity. These results
      identify MLKs as targets of CEP-1347 in the JNK signaling cascade and demonstrate
      that CEP-1347 can block MLK-induced cell death.

PMID- 11325963
TI  - Mitochondrial targeted cytochrome P450 2E1 (P450 MT5) contains an intact N
      terminus and requires mitochondrial specific electron transfer proteins for
      activity.
AB  - Hepatic mitochondria contain an inducible cytochrome P450, referred to as P450
      MT5, which cross-reacts with antibodies to microsomal cytochrome P450 2E1. In the
      present study, we purified, partially sequenced, and determined enzymatic
      properties of the rat liver mitochondrial form. The mitochondrial cytochrome P450
      2E1 was purified from pyrazole-induced rat livers using a combination of
      hydrophobic and ion-exchange chromatography. Mass spectrometry analysis of
      tryptic fragments of the purified protein further ascertained its identity. N
      terminal sequencing of the purified protein showed that its N terminus is
      identical to that of the microsomal cytochrome P450 2E1. In reconstitution
      experiments, the mitochondrial cytochrome P450 2E1 displayed the same catalytic
      activity as the microsomal counterpart, although the activity of the
      mitochondrial enzyme was supported exclusively by adrenodoxin and adrenodoxin
      reductase. Mass spectrometry analysis of tryptic fragments and also immunoblot
      analysis of proteins with anti-serine phosphate antibody demonstrated that the
      mitochondrial cytochrome P450 2E1 is phosphorylated at a higher level compared
      with the microsomal counterpart. A different conformational state of the
      mitochondrial targeted cytochrome P450 2E1 (P450 MT5) is likely to be responsible
      for its observed preference for adrenodoxin and adrenodoxin reductase electron
      transfer proteins.

PMID- 11325964
TI  - Calmodulin activates intersubunit electron transfer in the neuronal nitric-oxide
      synthase dimer.
AB  - Neuronal nitric oxide synthase (nNOS) is composed of an oxygenase domain that
      binds heme, (6R)-tetrahydrobiopterin, and Arg, coupled to a reductase domain that
      binds FAD, FMN, and NADPH. Activity requires dimeric interaction between two
      oxygenase domains and calmodulin binding between the reductase and oxygenase
      domains, which triggers electron transfer between flavin and heme groups. We
      constructed four different nNOS heterodimers to determine the path of calmodulin
      induced electron transfer in a nNOS dimer. A predominantly monomeric mutant of
      rat nNOS (G671A) and its Arg binding mutant (G671A/E592A) were used as full
      length subunits, along with oxygenase domain partners that either did or did not
      contain the E592A mutation. The E592A mutation prevented Arg binding to the
      oxygenase domain in which it was present. It also prevented NO synthesis when it
      was located in the oxygenase domain adjacent to the full-length subunit. However,
      it had no effect when present in the full-length subunit (i.e. the subunit
      containing the reductase domain). The active heterodimer (G671A/E592A full-length
      subunit plus wild type oxygenase domain subunit) showed remarkable similarity
      with wild type homodimeric nNOS in its catalytic responses to five different
      forms and chimeras of calmodulin. This reveals an active involvement of
      calmodulin in supporting transelectron transfer between flavin and heme groups on
      adjacent subunits in nNOS. In summary, we propose that calmodulin functions to
      properly align adjacent reductase and the oxygenase domains in a nNOS dimer for
      electron transfer between them, leading to NO synthesis by the heme.

PMID- 11325965
TI  - The profibrinolytic enzyme subtilisin NAT purified from Bacillus subtilis Cleaves
      and inactivates plasminogen activator inhibitor type 1.
AB  - In this report, we demonstrate an interaction between subtilisin NAT (formerly
      designated BSP, or nattokinase), a profibrinolytic serine proteinase from
      Bacillus subtilis, and plasminogen activator inhibitor 1 (PAI-1). Subtilisin NAT
      was purified to homogeneity (molecular mass, 27.7 kDa) from a saline extract of
      B. subtilis (natto). Subtilisin NAT appeared to cleave active recombinant
      prokaryotic PAI-1 (rpPAI-1) into low molecular weight fragments. Matrix-assisted
      laser desorption/ionization in combination with time-of-flight mass spectroscopy
      and peptide sequence analysis revealed that rpPAI-1 was cleaved at its reactive
      site (P1-P1': Arg(346)-Met(347)). rpPAI-1 lost its specific activity after
      subtilisin NAT treatment in a dose-dependent manner (0.02-1.0 nm; half-maximal
      effect at approximately 0.1 nm). Subtilisin NAT dose dependently (0.06-1 nm)
      enhanced tissue-type plasminogen activator-induced fibrin clot lysis both in the
      absence of rpPAI-1 (48 +/- 1.4% at 1 nm) and especially in the presence of rpPAI
      1 (78 +/- 2.0% at 1 nm). The enhancement observed in the absence of PAI-1 seems
      to be induced through direct fibrin dissolution by subtilisin NAT. The stronger
      enhancement by subtilisin NAT of rpPAI-1-enriched fibrin clot lysis seems to
      involve the cleavage and inactivation of active rpPAI-1. This mechanism is
      suggested to be important for subtilisin NAT to potentiate fibrinolysis.

PMID- 11325966
TI  - GGA*TCC-interrupted triplets in long GAA*TTC repeats inhibit the formation of
      triplex and sticky DNA structures, alleviate transcription inhibition, and reduce
      genetic instabilities.
AB  - Large expansions of GAA.TTC repeats in the first intron of the frataxin (X25)
      gene are the principal mutation responsible for Friedreich's ataxia (FRDA).
      Sticky DNA, based on R.R.Y triplexes, was found at the expanded GAA.TTC repeats
      from FRDA patients. The (GAAGGA.TCCTTC)(65) repeat occurs in the same frataxin
      locus but is nonpathogenic and does not form sticky DNA. To elucidate the
      behavior of sticky DNA, we introduced various extents of GGA.TCC interruptions
      into the long GAA.TTC repeat. More than 20% of GGA.TCC interruptions abolished
      the formation of sticky DNA. However, the GAA.TTC repeats with less than 11% of
      GGA.TCC interruptions formed triplexes and/or sticky DNA similar to the
      uninterrupted repeat sequence. These triplexes showed different P1 nuclease
      sensitivities, and the GGA.TCC interruptions were slightly more sensitive than
      the surrounding GAA.TTC repeats. Furthermore, genetic instability investigations
      in Escherichia coli revealed that a small number (4%) of interruptions
      substantially stabilized the long GAA.TTC tracts. Furthermore, the greater the
      extent of interruptions of the GAA.TTC repeats, the less inhibition of in vitro
      transcription was observed, as expected, based on the capacity of interruptions
      to inhibit the formation of sticky DNA. We propose that the interruptions
      introduce base mismatches into the R.R.Y triplex, which explains the observed
      chemical and biological properties.

PMID- 11325967
TI  - X-ray crystal structure of the trimeric N-terminal domain of gephyrin.
AB  - Gephyrin is a ubiquitously expressed protein that, in the central nervous system,
      forms a submembraneous scaffold for anchoring inhibitory neurotransmitter
      receptors in the postsynaptic membrane. The N- and C-terminal domains of gephyrin
      are homologous to the Escherichia coli enzymes MogA and MoeA, respectively, both
      of which are involved in molybdenum cofactor biosynthesis. This enzymatic pathway
      is highly conserved from bacteria to mammals, as underlined by the ability of
      gephyrin to rescue molybdenum cofactor deficiencies in different organisms. Here
      we report the x-ray crystal structure of the N-terminal domain (amino acids 2
      188) of rat gephyrin at 1.9-A resolution. Gephyrin-(2-188) forms trimers in
      solution, and a sequence motif thought to be involved in molybdopterin binding is
      highly conserved between gephyrin and the E. coli protein. The atomic structure
      of gephyrin-(2-188) resembles MogA, albeit with two major differences. The path
      of the C-terminal ends of gephyrin-(2-188) indicates that the central and C
      terminal domains, absent in this structure, should follow a similar 3-fold
      arrangement as the N-terminal region. In addition, a central beta-hairpin loop
      found in MogA is lacking in gephyrin-(2-188). Despite these differences, both
      structures show a high degree of surface charge conservation, which is consistent
      with their common catalytic function.

PMID- 11325968
TI  - Transmembrane-4 superfamily proteins associate with activated protein kinase C
      (PKC) and link PKC to specific beta(1) integrins.
AB  - Translocation of conventional protein kinases C (PKCs) to the plasma membrane
      leads to their specific association with transmembrane-4 superfamily (TM4SF;
      tetraspanin) proteins (CD9, CD53, CD81, CD82, and CD151), as demonstrated by
      reciprocal co-immunoprecipitation and covalent cross-linking experiments.
      Although formation and maintenance of TM4SF-PKC complexes are not dependent on
      integrins, TM4SF proteins can act as linker molecules, recruiting PKC into
      proximity with specific integrins. Previous studies showed that the extracellular
      large loop of TM4SF proteins determines integrin associations. In contrast,
      specificity for PKC association probably resides within cytoplasmic tails or the
      first two transmembrane domains of TM4SF proteins, as seen from studies with
      chimeric CD9 molecules. Consistent with a TM4SF linker function, only those
      integrins (alpha(3)beta(1), alpha(6)beta(1), and a chimeric "X3TC5" alpha(3)
      mutant) that associated strongly with tetraspanins were found in association with
      PKC. We propose that PKC-TM4SF-integrin structures represent a novel type of
      signaling complex. The simultaneous binding of TM4SF proteins to the
      extracellular domains of the integrin alpha(3) subunit and to intracellular PKC
      helps to explain why the integrin alpha3 extracellular domain is needed for both
      intracellular PKC recruitment and PKC-dependent phosphorylation of the alpha(3)
      integrin cytoplasmic tail.

PMID- 11325969
TI  - Insulin induces suppressor of cytokine signaling-3 tyrosine phosphorylation
      through janus-activated kinase.
AB  - Suppressor of cytokine signaling (SOCS) proteins were originally described as
      cytokine-induced molecules involved in negative feedback loops. We have shown
      that SOCS-3 is also a component of the insulin signaling network (). Indeed,
      insulin leads to SOCS-3 expression in 3T3-L1 adipocytes. Once produced, SOCS-3
      binds to phosphorylated tyrosine 960 of the insulin receptor and inhibits insulin
      signaling. Now we show that in 3T3-L1 adipocytes and in transfected COS-7 cells
      insulin leads to SOCS-3 tyrosine phosphorylation. This phosphorylation takes
      place on Tyr(204) and is dependent upon a functional SOCS-3 SH2 domain. Purified
      insulin receptor directly phosphorylates SOCS-3. However, in intact cells, a
      mutant of the insulin receptor, IRY960F, unable to bind SOCS-3, was as efficient
      as the wild type insulin receptor to phosphorylate SOCS-3. Importantly, IRY960F
      is as potent as the wild type insulin receptor to activate janus-activated kinase
      (Jak) 1 and Jak2. Furthermore, expression of a dominant negative form of Jak2
      inhibits insulin-induced SOCS-3 tyrosine phosphorylation. As transfected Jaks
      have been shown to cause SOCS-3 phosphorylation, we propose that insulin induces
      SOCS-3 phosphorylation through Jak activation. Our data indicate that SOCS-3
      belongs to a class of tyrosine-phosphorylated insulin signaling molecules, the
      phosphorylation of which is not dependent upon a direct coupling with the insulin
      receptor but relies on the Jaks.

PMID- 11325970
TI  - Binding of ATP to the fructose-2,6-bisphosphatase domain of chicken liver 6
      phosphofructo-2-kinase/fructose-2,6-bisphosphatase leads to activation of its 6
      phosphofructo-2-kinase.
AB  - To understand the mechanism by which the activity of the 6-phosphofructo-2-kinase
      (6PF-2K) of chicken liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase is
      stimulated by its substrate ATP, we studied two mutants of the enzyme. Mutation
      of either Arg-279, the penultimate basic residue within the Walker A nucleotide
      binding fold in the bisphosphatase domain, or Arg-359 to Ala eliminated the
      activation of the chicken 6PF-2K by ATP. Binding analysis by fluorescence
      spectroscopy using 2'(3')-O-(N-methylanthraniloyl)-ATP revealed that the kinase
      domains of these two mutants, unlike that of the wild type enzyme, showed no
      cooperativity in ATP binding and that the mutant enzymes possess only the high
      affinity ATP binding site, suggesting that the ATP binding site on the
      bisphosphatase domain represents the low affinity site. This conclusion was
      supported by the result that the affinity of ATP for the isolated bisphosphatase
      domain is similar to that for the low affinity site in the wild type enzyme. In
      addition, we found that the 6PF-2K of a chimeric enzyme, in which the last 25
      residues of chicken enzyme were replaced with those of the rat enzyme, could not
      be activated by ATP, despite the fact that the ATP-binding properties of this
      chimeric enzyme were not different from those of the wild type chicken enzyme.
      These results demonstrate that activation of the chicken 6PF-2K by ATP may result
      from allosteric binding of ATP to the bisphosphatase domain where residues Arg
      279 and Arg-359 are critically involved and require specific C-terminal
      sequences.

PMID- 11325971
TI  - Identification of a simian immunodeficiency virus reverse transcriptase variant
      with enhanced replicational fidelity in the late stage of viral infection.
AB  - Genomic hypermutation of human and simian immunodeficiency viruses (HIV and SIV)
      enables these viruses to adapt and escape from various types of anti-viral
      selection by altering the molecular properties of viral gene products. In this
      study, we examined whether the biochemical and catalytic properties of SIV DNA
      polymerases (reverse transcriptases; RT) can change during the course of viral
      infection. For this test, we analyzed RTs obtained from two SIV clones, SIVMNE
      CL8 and SIVMNE 170. SIVMNE 170 was isolated during the late symptomatic phase of
      infection with the parental strain, SIVMNE CL8. We found these two RTs have
      identical DNA polymerase specific activities and kinetics with three different
      DNA and RNA templates. In addition, the processivity of these two SIV RT proteins
      were also similar. However, as demonstrated by a misincorporation assay, the
      SIVMNE 170 RT showed much higher fidelity than SIVMNE CL8. The fidelity
      difference between these two SIV RTs was also confirmed by a steady state kinetic
      fidelity assay. These findings suggest that the fidelity of lentiviral RTs may
      change during the course of viral infection, possibly in response to alterations
      of host anti-viral immune capability. In addition, our sequence analysis of these
      two RT genes proposes possible structural strategies that the virus may employ to
      alter RT fidelity.

PMID- 11325972
TI  - The serpin inhibitory mechanism is critically dependent on the length of the
      reactive center loop.
AB  - The recent crystallographic structure of a serpin-protease complex revealed that
      protease inactivation results from a disruption of the catalytic site
      architecture caused by the displacement of the catalytic serine. We hypothesize
      that inhibition depends on the length of the N-terminal portion of the reactive
      center loop, to which the active serine is covalently attached. To test this,
      alpha(1)-antitrypsin Pittsburgh variants were prepared with lengthened and
      shortened reactive center loops. The rates of inhibition of factor Xa and of
      complex dissociation were measured. The addition of one residue reduced the
      stability of the complex more than 200,000-fold, and the addition of two residues
      reduced it by more than 1,000,000-fold, whereas the deletion of one or two
      residues lowered the efficiency of inhibition and increased the stability of the
      complex (2-fold). The deletion of more than two residues completely converted the
      serpin into a substrate. Similar results were obtained for the alpha(1)
      antitrypsin variants with thrombin and for PAI-1 and PAI-2 with their common
      target tissue plasminogen activator. We conclude that the length of the serpin
      reactive center loop is critical for its mechanism of inhibition and is precisely
      regulated to balance the efficiency of inhibition and stability of the final
      complex.

PMID- 11325973
TI  - Structural determinants of cold adaptation and stability in a large protein.
AB  - The heat-labile alpha-amylase from an antarctic bacterium is the largest known
      protein that unfolds reversibly according to a two-state transition as shown by
      differential scanning calorimetry. Mutants of this enzyme were produced, carrying
      additional weak interactions found in thermostable alpha-amylases. It is shown
      that single amino acid side chain substitutions can significantly modify the
      melting point T(m), the calorimetric enthalpy Delta H(cal), the cooperativity and
      reversibility of unfolding, the thermal inactivation rate constant, and the
      kinetic parameters k(cat) and K(m). The correlation between thermal inactivation
      and unfolding reversibility displayed by the mutants also shows that stabilizing
      interactions increase the frequency of side reactions during refolding, leading
      to intramolecular mismatches or aggregations typical of large proteins. Although
      all mutations were located far from the active site, their overall trend is to
      decrease both k(cat) and K(m) by rigidifying the molecule and to protect mutants
      against thermal inactivation. The effects of these mutations indicate that the
      cold-adapted alpha-amylase has lost a large number of weak interactions during
      evolution to reach the required conformational plasticity for catalysis at low
      temperatures, thereby producing an enzyme close to the lowest stability allowing
      maintenance of the native conformation.

PMID- 11325974
TI  - Group A streptococcal genotypes from pediatric throat isolates in Rome, Italy.
AB  - In a study assessing genetic diversity, 114 group A streptococcus (GAS) isolates
      were recovered from pediatric pharyngitis patients in Rome, Italy. These isolates
      comprised 22 different M protein gene (emm) sequence types, 14 of which were
      associated with a distinct serum opacity factor/fibronectin binding protein gene
      (sof) sequence type. Isolates with the same emm gene sequence type generally
      shared a highly conserved chromosomal macrorestriction profile. In three
      instances, isolates with dissimilar macrorestriction profiles had identical emm
      types; in each of these cases multilocus sequence typing revealed that isolates
      with the same emm type were clones having the same allelic profiles. Ninety-eight
      percent of the pharyngeal isolates had emm types previously found to be highly
      associated with mga locus gene patterns commonly found in pharyngeal GAS
      isolates.

PMID- 11325975
TI  - Secondary typing of Mycobacterium tuberculosis isolates with matching IS6110
      fingerprints from different geographic regions of the United States.
AB  - Fifty-nine isolates of Mycobacterium tuberculosis obtained from different states
      in the United States and representing 25 interstate clusters were investigated.
      These clusters were identified by computer-assisted analysis of DNA fingerprints
      submitted during 1996 and 1997 by different laboratories participating in the CDC
      National Genotyping and Surveillance Network. Isolates were fingerprinted with
      the IS6110 right-hand probe (IS6110-3'), the IS6110 left-hand probe (IS6110-5'),
      and the probe pTBN12, containing the polymorphic GC-rich sequence (PGRS).
      Spoligotyping based on the polymorphism in the 36-bp direct-repeat locus was also
      performed. As a control, 43 M. tuberculosis isolates in 17 clusters obtained from
      patients in Arkansas during the study period were analyzed. Of the 25 interstate
      clusters, 19 were confirmed as correctly clustered when all the isolates were
      analyzed on the same gel using the IS6110-3' probe. Of the 19 true IS6110-3'
      clusters, 10 (53%) were subdivided by one or more secondary typing methods.
      Clustering of the control group was virtually identical by all methods. Of the
      three different secondary typing methods, spoligotyping was the least
      discriminating. IS6110-5' fingerprinting was as discriminating as PGRS
      fingerprinting. The data indicate that the IS6110-5' probe not only is a useful
      secondary typing method but also probably would prove to be a more useful primary
      typing method for a genotyping network which involves isolates from different
      geographic regions.

PMID- 11325976
TI  - Evaluation of the Hexaplex assay for detection of respiratory viruses in
      children.
AB  - The Hexaplex assay (Prodesse, Inc., Milwaukee, Wis.) is a multiplex reverse
      transcriptase (RT)-PCR assay for the detection of parainfluenza virus types 1, 2,
      and 3, respiratory syncytial virus (RSV) types A and B, and influenza virus types
      A and B. We evaluated the Hexaplex assay in comparison with conventional viral
      cell cultures and rapid enzyme immunoassays (EIAs) for RSV (Directigen; Becton
      Dickinson Inc., Cockeysville, Md.) and influenza A virus (Abbott Test Pack;
      Abbott Laboratories, Abbott Park, Ill.) for the detection of respiratory viruses
      from pediatric respiratory specimens obtained from children seen at Children's
      Hospital of Wisconsin from December 1997 through May 1998. A total of 363
      respiratory specimens were evaluated. The tissue culture prevalence of
      parainfluenza virus during this period of time was low (1.1%). The sensitivity,
      specificity, and positive and negative predictive value of Hexaplex compared to
      tissue culture for the detection of parainfluenza virus were 100, 95.8, 19.0, and
      100%, respectively. Only one specimen was determined to contain influenza B virus
      by Hexaplex; it was tissue culture negative. A specimen was considered to contain
      RSV or influenza A virus when it was either culture positive or culture negative
      but Hexaplex and EIA positive. Prior to the analysis of discrepant results, the
      sensitivity, specificity, and positive and negative predictive value for the
      detection of RSV were 91.2, 100, 100, and 98.0%, respectively, for tissue
      culture; 84.5, 100, 100, and 96.6% for EIA; and 98.5, 91.5, 72.8, and 99.6% for
      Hexaplex, respectively. The sensitivity, specificity, and positive and negative
      predictive value for the detection of influenza A virus prior to the analysis of
      discrepant results were 100, 100, 100, and 100%, respectively, for culture, 78.0,
      100, 100, and 89.4% for EIA, respectively, and 95.1, 94.1, 67.2, and 99.3% for
      Hexaplex, respectively. Culture- and/or EIA-negative, Hexaplex-positive specimens
      were analyzed by a second RT-PCR assay which used primers specific for a
      different genomic region than that used in the Hexaplex assay. After analysis of
      these discrepant results, the sensitivity, specificity, and positive and negative
      predictive value for the detection of RSV were 74.3, 100, 100, and 93.5%,
      respectively, for tissue culture; 70.3, 100, 100, and 92.5% for EIA; and 98.6,
      97.4, 91.2, and 99.6% for Hexaplex. The sensitivity, specificity, and positive
      and negative predictive value for the detection of influenza A virus were 83.3,
      100, 100, and 97.4%, respectively, for tissue culture; 69.4, 100, 100, and 83.3%
      for EIA; and 95.8, 98.7, 92.0, and 99.3% for Hexaplex. Hexaplex is a rapid,
      sensitive, and specific method for the detection of the seven most common
      respiratory viruses in children.

PMID- 11325977
TI  - Outbreak of Pichia anomala infection in the pediatric service of a tertiary-care
      center in Northern India.
AB  - An outbreak of nosocomial fungemia due to the unusual yeast, Pichia anomala
      occurred in the pediatric wards of our hospital over a period of 23 months (April
      1996 to February 1998). A total of 379 neonates and children (4.2% admissions)
      were infected. The probable index case was admitted to the pediatric emergency
      ward, with subsequent transmission to the premature nursery, pediatric intensive
      care units, and other children wards. Carriage on the hands of health care
      personnel was likely to be responsible for dissemination of the fungus. The
      outbreak could only be controlled after a health education campaign to improve
      hand-washing practices was instituted and after nystatin-fluconazole prophylaxis
      to all premature neonates and high-risk infants was introduced. In a case-control
      study, we identified a lower gestational age, a very low birth weight (<1,500 g),
      and a longer duration of hospital stay as significant risk factors associated
      with P. anomala fungemia in premature neonates. We conducted a culture prevalence
      survey of 50 consecutive premature neonates and found that 28% were colonized
      with P. anomala at a skin or mucosal site on the date of delivery and that 20% of
      these neonates subsequently developed P. anomala fungemia. We performed
      multilocus enzyme electrophoresis on 40 P. anomala outbreak isolates (including
      patient and health care workers' hand isolates), and the results suggested that
      these isolates were identical. Our study highlights the importance of P. anomala
      as an emerging nosocomial fungal pathogen.

PMID- 11325978
TI  - Detection and culture of Bartonella quintana, Serratia marcescens, and
      Acinetobacter spp. from decontaminated human body lice.
AB  - As part of a survey for trench fever among homeless people in Marseilles, France,
      we attempted isolation of Bartonella quintana from body lice. A decontamination
      protocol of immersion in 70% ethanol with 0.2% iodine was devised and was tested
      with a laboratory colony of body lice. Lice which had been experimentally
      contaminated with either Escherichia coli, Staphylococcus epidermidis, or
      Acinetobacter spp. were successfully decontaminated, and this process did not
      prevent the culture of B. quintana from these lice. One hundred sixty-one lice
      obtained from homeless patients were studied by the protocol. B. quintana was
      isolated on axenic medium from 15 of 161 body lice and was detected in 41 of 161
      lice by PCR. Acinetobacter spp. and Serratia marcescens were also isolated from
      body lice. The sensitivities of PCR and culture of B. quintana were 98 and 36%,
      respectively. These procedures may be useful for epidemiologic studies of trench
      fever and for the recovery of strains for characterization and comparison.

PMID- 11325979
TI  - Genetic diversity of Neisseria lactamica strains from epidemiologically defined
      carriers.
AB  - We assessed the genetic diversity of 26 Neisseria lactamica strains from
      epidemiologically related sources, i.e., groups of kindergartens and primary
      schools in three Bavarian towns, by the partial sequencing of the argF, rho,
      recA, and 16S ribosomal genes. We found a total of 17 genotypes, of which 12 were
      found only in one strain. The genotypes comprised 5 alleles of the argF gene, 9
      of rho, 8 of recA, and 10 of the 16S ribosomal DNA. Sequence analysis by
      determination of homoplasy ratios and split decomposition analysis revealed
      abundant recombination within N. lactamica.

PMID- 11325980
TI  - Helicobacter sp. flexispira bacteremia in an immunocompetent young adult.
AB  - A young immunocompetent patient was admitted for a febrile illness with malaise,
      arthralgias, painful leg swelling, and polyserositis. Shortly prior to becoming
      ill, the patient had traveled to the Northern African desert. The symptoms
      disappeared during treatment with antibiotics (doxycycline and ceftriaxone) but
      recurred twice after stopping therapy. A motile gram-negative fusiform rod was
      isolated from a blood culture taken on the first admission. Analysis of the 16S
      rRNA gene of the blood culture isolate revealed close similarity with
      Helicobacter sp. flexispira taxon 8 (99.9% identity), a species that was
      previously reported as "Flexispira rappini." This is the first reported case of a
      recurrent Helicobacter sp. flexispira bacteremia in an adult, immunocompetent
      patient.

PMID- 11325981
TI  - Use of recombinant mitogillin for improved serodiagnosis of Aspergillus fumigatus
      associated diseases.
AB  - During human infection, Aspergillus fumigatus secretes a 18-kDa protein that can
      be detected as an immunodominant antigen in the urine of infected patients.
      Recently, this protein was shown to be mitogillin, a ribotoxin that cleaves a
      single phosphodiester bond of the 29S rRNA of eukaryotic ribosomes. We proved the
      immunogenic capacity of mitogillin in a rabbit animal model, indicating its
      usefulness as an antigen for serological diagnosis of invasive aspergillosis. The
      mitogillin gene from A. fumigatus was transferred from plasmid pMIT+ to
      expression vector pQE30 and expressed in Escherichia coli as a fusion protein.
      Purified recombinant mitogillin was recognized by serum immunoglobulin G (IgG) of
      polyclonal rabbit sera that were obtained by immunization with purified native
      mitogillin. Consequently, we developed an enzyme-linked immunosorbent assay for
      detection of IgG, IgM, and IgA antibodies to recombinant mitogillin. In serum
      samples of patients suffering from aspergilloma (AO; n = 32), invasive pulmonary
      aspergillosis (IPA; n = 42), or invasive disseminated aspergillosis (IDA; n =
      40), a good correlation of production of IgG antibody against mitogillin and
      clinical disease was observed (for patients with AO, 100% [32 of 32] were
      positive; for patients with IPA, 64% [31 of 42] were positive; for patients with
      IDA, 60% [24 of 40] were positive). In contrast, positive titers for serum IgG
      and IgM antibodies against mitogillin were found in only 1.3% of the serum
      samples of healthy volunteers and positive titers for IgA antibody were found in
      only 1.0% of the serum samples of healthy volunteers (n = 307; specificity =
      95.4%). These results indicate that recombinant mitogillin expressed in E. coli
      can be used for improvement of the serodiagnosis of A. fumigatus-associated
      diseases.

PMID- 11325982
TI  - Genetic polymorphism of Aspergillus fumigatus in clinical samples from patients
      with invasive aspergillosis: investigation using multiple typing methods.
AB  - The genotypes of 52 strains of Aspergillus fumigatus isolated from 12 patients
      with invasive aspergillosis were investigated using three typing methods (random
      amplified polymorphic DNA, sequence-specific DNA polymorphism, and microsatellite
      polymorphism) combined with multilocus enzyme electrophoresis. Isolates were from
      patients hospitalized in three different geographic areas (Lyon, France;
      Grenoble, France; and Milan, Italy). In each case, the genetic polymorphism of
      several colonies (two to five) within the first respiratory clinical sample was
      studied. For the 52 isolates tested, random amplified polymorphic DNA identified
      8 different genotypes, sequence-specific DNA polymorphism identified 9 different
      types, and microsatellite polymorphism identified 14 types. A combination of
      these results with multilocus enzyme electrophoresis study identified 25
      different types within the sample studied. We identified 3 patients (of the 12
      studied) who carried a single genotype; 6 patients were infected by two
      genotypes, 1 patient had four genotypes, while the last patient had five. A
      combination of typing methods provided better discrimination than the use of a
      single method. Typing methods revealed a population structure within each
      geographical site, suggesting that the epidemiology of A. fumigatus should be
      considered separately for each of these geographic areas. This study demonstrates
      the usefulness of combining several typing methods in reaching an understanding
      of the epidemiology of A. fumigatus and clarifies whether it is sufficient to
      type one isolate from each specimen to determine the strain involved in invasive
      aspergillosis.

PMID- 11325983
TI  - Characterization of AfaE adhesins produced by extraintestinal and intestinal
      human Escherichia coli isolates: PCR assays for detection of Afa adhesins that do
      or do not recognize Dr blood group antigens.
AB  - Operons of the afa family are expressed by pathogenic Escherichia coli strains
      associated with intestinal and extraintestinal infections in humans and animals.
      The recently demonstrated heterogeneity of these operons (L. Lalioui, M. Jouve,
      P. Gounon, and C. Le Bouguenec, Infect. Immun. 67:5048-5059, 1999) was used to
      develop a new PCR assay for detecting all the operons of the afa family with a
      single genetic tool. This PCR approach was validated by investigating three
      collections of human E. coli isolates originating from the stools of infants with
      diarrhea (88 strains), the urine of patients with pyelonephritis (97 strains),
      and the blood of cancer patients (115 strains). The results obtained with this
      single test and those previously obtained with several PCR assays were closely
      correlated. The AfaE adhesins encoded by the afa operons are variable,
      particularly with respect to the primary sequence encoded by the afaE gene. The
      receptor binding specificities have not been determined for all of these
      adhesins; some recognize the Dr blood group antigen (Afa/Dr(+) adhesins) on the
      human decay-accelerating factor (DAF) as a receptor, and others (Afa/Dr(-)
      adhesins) do not. Thus, the afa operons detected in this study were characterized
      by subtyping the afaE gene using specific PCRs. In addition, the DAF-binding
      capacities of as-yet-uncharacterized AfaE adhesins were tested by various
      cellular approaches. The afaE8 subtype (Afa/Dr(-) adhesin) was found to
      predominate in afa-positive isolates from sepsis patients (75%); it was frequent
      in afa-positive pyelonephritis E. coli (55.5%) and absent from diarrhea
      associated strains. In contrast, Afa/Dr(+) strains (regardless of the afaE
      subtype) were associated with both diarrhea (100%) and extraintestinal infections
      (44 and 25% in afa-positive pyelonephritis and sepsis strains, respectively).
      These data suggest that there is an association between the subtype of AfaE
      adhesin and the physiological site of the infection caused by afa-positive
      strains.

PMID- 11325985
TI  - Detection of Chlamydia trachomatis and Neisseria gonorrhoeae by enzyme
      immunoassay, culture, and three nucleic acid amplification tests.
AB  - The purpose of this study was to evaluate and compare three commercially
      available nucleic acid amplification tests (NAATs) for the detection of Neisseria
      gonorrhoeae and Chlamydia trachomatis. Roche PCR and Becton Dickinson strand
      displacement amplification (SDA) were performed on 733 endocervical swab
      specimens from commercial sex workers. Abbott ligase chain reaction (LCR) was
      performed on a subset of 396 samples. Endocervical specimens from all women were
      also tested by culture for N. gonorrhoeae and by Syva MicroTrak enzyme
      immunoassay (EIA) for C. trachomatis. A positive N. gonorrhoeae result was
      defined as a positive result by culture or by two NAATs, and a positive C.
      trachomatis result was defined as a positive result by two tests. According to
      these definitions, the sensitivities and specificities for the subsample of 396
      specimens of N. gonorrhoeae culture, PCR, SDA, and LCR were 69.8, 95.2, 88.9, and
      88.9% and 100, 99.4, 100, and 99.1%, respectively; the sensitivities and
      specificities of C. trachomatis EIA, PCR, SDA, and LCR were 42.0, 98.0, 94.0, and
      90.0% and 100, 98.0, 100, and 98.6%, respectively. The performance
      characteristics of N. gonorrhoeae culture, PCR, and SDA and C. trachomatis EIA,
      PCR, and SDA for all 733 specimens were defined without inclusion of LCR results
      and by discrepant analysis after resolution of discordant N. gonorrhoeae PCR
      results and of discordant C. trachomatis EIA and PCR results by LCR testing. The
      sensitivities of N. gonorrhoeae culture, PCR, and SDA before and after LCR
      resolution were 67.8, 95.7, and 93.9% and 65, 95.8, and 90.0%, respectively. The
      sensitivities of C. trachomatis EIA, PCR, and SDA decreased from 39.4, 100, and
      100% to 38.7, 98.7, and 94.7%, respectively. All three NAATs proved to be
      superior to N. gonorrhoeae culture and to C. trachomatis EIA. The accuracies of
      the different NAATs were quite similar. SDA was the only amplification assay with
      100% specificity for detection of both N. gonorrhoeae and C. trachomatis in
      endocervical specimens.

PMID- 11325984
TI  - iceA genotypes of Helicobacter pylori strains isolated from Brazilian children
      and adults.
AB  - Data concerning the geographic distribution of iceA alleles are scarce, and
      information on the association of the gene with the disease is rare and still
      controversial. Furthermore, no such study has been developed in Brazil, where
      duodenal ulcer and gastric adenocarcinoma are very common. We investigated, by
      PCR, the frequency of iceA alleles and cagA status in Helicobacter pylori strains
      isolated from 142 patients (62 children and 80 adults; 66 female; mean age, 30.0
      years; age range, 3 to 78 years) with gastritis, duodenal ulcer, or gastric
      adenocarcinoma. iceA was identified in bacterium samples obtained from all
      patients. Eleven (7.7%) of them were infected with multiple strains. Among the
      patients with nonmixed infection, iceA2 allele was detected in 118 (90.1%). iceA2
      allele was associated with ulcer (P = 0.02) and with carcinoma (P = 0.001). iceA2
      amplicons of 229, 334, or 549 bp were detected, but none of them was associated
      with the patient's disorder. iceA2 strains were more frequent in patients older
      than 7 years (P = 0.001). The gene was also more frequent in strains obtained
      from males (P = 0.02). cagA was more common in strains obtained from carcinoma (P
      = 0.0008) and ulcer patients (P < 0.006). cagA-positive strains were more
      frequent in children older than 7 years (P < 0.003). No association between cagA
      status and sex was found (P = 0.28). In conclusion, we think iceA should not be
      used as a reliable marker for predicting the clinical outcome of H. pylori
      infection.

PMID- 11325986
TI  - Outer membrane proteins and DNA profiles in strains of Haemophilus parasuis
      recovered from systemic and respiratory sites.
AB  - Polyserositis caused by Haemophilus parasuis is an important disease that affects
      mostly weaned pigs. Recent studies have shown that virulence can differ among
      strains recovered from distinct body sites and also that it may be related to the
      presence of certain outer membrane proteins (OMPs). The objective of this study
      was to compare the OMP and DNA profiles of H. parasuis strains isolated from
      systemic and respiratory sites from diseased and healthy pigs. Strains evaluated
      in this study were processed using sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis and repetitive-PCR techniques. Two experiments were conducted in
      order to better define the relationship among genotype, phenotype, and site of
      isolation. Experiment 1 included 53 H. parasuis isolates recovered from healthy
      and diseased pigs from unrelated herds. Experiment 2 included 31 isolates of H.
      parasuis obtained from diseased pigs involved in an outbreak in a large,
      multifarm system. Results showed that strains recovered from systemic sites had
      more homogeneous OMP and DNA profiles than those isolated from respiratory sites.
      Evaluation of isolates involved in the multifarm outbreak showed that only two H.
      parasuis strains were causing disease. These strains had homogeneous OMP and DNA
      profiles. However, it was noted that these two parameters were unrelated, since
      strains classified in the same genotype group expressed different OMP profiles.
      The homogeneity of OMP and DNA profiles of strains isolated from systemic sites
      strongly suggests the existence of clonal relationships between virulent strains
      and also suggests that expression of certain OMP profiles may be related to
      virulence.

PMID- 11325987
TI  - Classification and identification of enterococci: a comparative phenotypic,
      genotypic, and vibrational spectroscopic study.
AB  - Rapid and accurate identification of enterococci at the species level is an
      essential task in clinical microbiology since these organisms have emerged as one
      of the leading causes of nosocomial infections worldwide. Vibrational
      spectroscopic techniques (infrared [IR] and Raman) could provide potential
      alternatives to conventional typing methods, because they are fast, easy to
      perform, and economical. We present a comparative study using phenotypic,
      genotypic, and vibrational spectroscopic techniques for typing a collection of 18
      Enterococcus strains comprising six different species. Classification of the
      bacteria by Fourier transform (FT)-IR spectroscopy in combination with
      hierarchical cluster analysis revealed discrepancies for certain strains when
      compared with results obtained from automated phenotypic systems, such as API and
      MicroScan. Further diagnostic evaluation using genotypic methods-i.e., PCR of the
      species-specific ligase and glycopeptide resistance genes, which is limited to
      the identification of only four Enterococcus species and 16S RNA sequencing, the
      "gold standard" for identification of enterococci-confirmed the results obtained
      by the FT-IR classification. These results were later reproduced by three
      different laboratories, using confocal Raman microspectroscopy, FT-IR attenuated
      total reflectance spectroscopy, and FT-IR microspectroscopy, demonstrating the
      discriminative capacity and the reproducibility of the technique. It is concluded
      that vibrational spectroscopic techniques have great potential as routine methods
      in clinical microbiology.

PMID- 11325988
TI  - Hepatitis C virus genotyping based on 5' noncoding sequence analysis (Trugene).
AB  - Hepatitis C virus (HCV) genotyping of samples from 184 patients with chronic HCV
      infection by the Trugene 5'NC genotyping kit, based on sequence analysis of the
      5' noncoding region (5' NCR), and the InnoLiPA assay was evaluated. In addition
      to these methods, the 184 samples were also analyzed by sequencing of part of the
      NS5B of the HCV genome after in-house PCR amplification, as a means of validating
      results obtained with the 5' NCR. The distribution of the genotypes typed by NS5B
      sequence analysis was as follows: 1a, 41 samples; 1b, 58 samples; 1d, 1 sample;
      2a, 5 samples; 2b, 2 samples; 2c, 7 samples; 3a, 46 samples; 4a, 7 samples; 4c, 1
      samples; 4e, 9 samples; 5a, 6 samples; 6a, 1 sample. The Trugene and InnoLiPA
      assays gave concordant results within HCV types in 100% of cases. The ability to
      discriminate at the subtype level was 76 and 74% for the Trugene and the InnoLiPA
      assays, respectively.

PMID- 11325989
TI  - Nested restriction site-specific PCR to detect and type hepatitis C virus (HCV):
      a rapid method to distinguish HCV subtype 1b from other genotypes.
AB  - Genotypic differentiation of hepatitis C virus (HCV) has become an integral part
      of clinical management and epidemiologic studies of hepatitis C infections. Thus,
      it is extremely important in areas such as the Czech Republic, where current
      instrumentation and kits for assessing HCV infection are too costly for
      widespread use. We describe a new and relatively inexpensive method called nested
      restriction site-specific PCR (RSS-PCR) that generates a "fingerprint" pattern to
      represent an HCV genotype without the use of restriction endonucleases and that
      specifically differentiates HCV genotype 1b from the other HCV genotypes. The RSS
      PCR method was applied directly to serum samples from patients with hepatitis C
      from the Czech Republic and from patients with known HCV genotypes from the
      United States. The method was validated by comparison of the subtype determined
      by RSS-PCR to the subtype determined from analysis of the 5' noncoding region
      (NC) or the nonstructural protein gene (NS5b) nucleotide sequence of HCV in these
      clinical samples. From 75 Czech samples containing HCV RNA, three distinct RSS
      PCR patterns were observed; 54 were predicted to contain subtype 1b, 19 were
      predicted to contain subtype 1a, and 2 were predicted to contain subtype 3a.
      Among 54 samples predicted to contain HCV genotype 1b, all were confirmed by
      their 5' NC or NS5b sequences to be subtype 1b. Thus, both the sensitivity and
      specificity of the RSS-PCR test for the differentiation of HCV subtype 1b from
      the others were 100%. While the assay described here was designed to specifically
      differentiate HCV subtype 1b from the other HCV genotypes, the RSS-PCR method can
      be modified to differentiate any HCV genotype or subtype of interest. Its
      simplicity and speed may provide new opportunities to study the epidemiology of
      HCV infections and the relationship between HCV genotypes and clinical outcome by
      more laboratories throughout the world.

PMID- 11325991
TI  - Effects of storage and type of blood collection tubes on hepatitis C virus level
      in whole blood samples.
AB  - In this study, we compared serum hepatitis C virus (HCV) RNA concentrations with
      HCV RNA concentrations in whole blood collection tubes, including two different
      types of EDTA tubes and nucleic acid stabilization tubes (NASTs). We also
      investigated the impact of a processing delay on HCV RNA concentration in these
      tubes. In NASTs, the mean HCV RNA concentration was comparable to the mean serum
      HCV RNA concentration at "date zero." In EDTA tubes, mean baseline HCV RNA
      concentrations were higher. Storage at room temperature up to 96 h did not result
      in a decline of HCV RNA concentration in any of the whole blood collection tubes.
      In NASTs, HCV RNA concentrations remained stable during the whole study period,
      whereas a significant increase of HCV RNA was observed in both types of EDTA
      tubes at 96 h compared to date zero. We concluded that HCV RNA remains stable in
      NASTs at room temperature for at least 96 h, allowing greater flexibility in
      sample collection and transport.

PMID- 11325990
TI  - Outbreak of vancomycin-resistant Enterococcus faecium of the phenotype VanB in a
      hospital in Warsaw, Poland: probable transmission of the resistance determinants
      into an endemic vancomycin-susceptible strain.
AB  - The first outbreak caused by vancomycin-resistant enterococci of the VanB
      phenotype in Poland was analyzed. It occurred in a single ward of a Warsaw
      hospital which is a specialized center for the treatment of hematological
      disorders. Between July 1999 and February 2000, 11 patients in the ward were
      found to be infected and/or colonized by Enterococcus faecium that was resistant
      in vitro to vancomycin and susceptible to teicoplanin. PCR analysis confirmed
      that the vancomycin-resistant E. faecium (VREM) isolates carried the vanB gene,
      which is responsible for the VanB phenotype. Pulsed-field gel electrophoresis
      (PFGE) typing revealed that the isolates belonged to four distinct PFGE types and
      that one of these was clearly predominant, including isolates collected from
      seven different patients. The isolates contained one or more copies of the vanB
      gene cluster of the identical, unique DraI/PagI (BspHI) restriction fragment
      length polymorphism type, which resided in either the same or different plasmid
      molecules or chromosomal regions. All this data suggested that the outbreak was
      due to both clonal spread of a single strain and horizontal transfer of
      resistance genes among nonrelated strains, which could be mediated by plasmids
      and/or by vanB gene cluster-containing transposons. The comparative analysis of
      vancomycin-susceptible E. faecium (VSEM) isolates collected from infections in
      the same ward at the time of the VREM outbreak has led to identification of a
      widespread VSEM strain that was possibly related to the major VREM clone. It is
      very likely that this endemic VSEM strain has acquired vancomycin-resistance
      determinants and that the acquisition occurred more than once during the
      outbreak.

PMID- 11325992
TI  - Comparison of results generated by serotyping, pulsed-field restriction analysis,
      ribotyping, and repetitive-sequence PCR used to characterize penicillin-resistant
      pneumococci from the United States.
AB  - One hundred forty-seven isolates of Streptococcus pneumoniae with high-level
      penicillin resistance collected during a national surveillance program in the
      United States were characterized by serotyping, pulsed-field restriction
      analysis, ribotyping, and repetitive-sequence (BOX element) PCR. The results
      generated by each method were compared by frequency of association to examine
      whether relationships existed between the various typing methods and
      statistically to determine association with the geographic source of the isolate
      or the age of the patient from whom the isolate was obtained. When the data were
      examined by pairwise analysis of individual strain classifications produced by
      each typing method, no statistically significant relationships between strain
      type, geographic location, or patient age were identified, suggesting that
      distinct clones of penicillin-resistant S. pneumoniae have been widely
      distributed throughout the United States. However, we did observed shared
      expression of two or three typing markers at a high frequency (>50%) among
      clusters of strains, indicating a certain level of concordance between the
      various typing methods used to classify penicillin-resistant S. pneumoniae.

PMID- 11325993
TI  - Replicate PCR testing and probit analysis for detection and quantitation of
      Chlamydia pneumoniae in clinical specimens.
AB  - Nucleic acid amplification of clinical specimens with low target concentration
      has variable sensitivity. We examined whether testing multiple aliquots of
      extracted DNA increased the sensitivity and reproducibility of Chlamydia
      pneumoniae detection by PCR. Nested and non-nested C. pneumoniae PCR assays were
      compared using 10 replicates of 16 serial dilutions of C. pneumoniae ATCC VR
      1310. The proportion positive versus the C. pneumoniae concentration was modeled
      by probit regression analysis. To validate the model, 10 replicates of 26
      previously positive patient specimens of peripheral blood mononuclear cells
      (PBMC), sputum, or nasopharyngeal swabs (NPS) were tested. The proportion of
      replicates that were positive varied with the concentration of C. pneumoniae in
      the sample. At concentrations above 5 infection-forming units (IFU)/ml, both
      nested and non-nested PCR assay sensitivities were 90% or greater. The nested PCR
      was more sensitive (median detection, 0.35 versus 0.61 IFU/ml; relative median
      detection, 0.58; 95% confidence interval, 0.31 to 0.99; P = 0.04). In clinical
      specimens, replicate PCR detected 15 of 26 (nested) versus 1 of 26 (non-nested, P
      < 0.001). For PBMC specimens, testing 1, 3, or 5 replicates detected 3, 5, or 9
      of 10 positive specimens, respectively. Median C. pneumoniae concentrations were
      estimated at 0.07 IFU/ml for PBMC and at <0.03 IFU/ml for NPS specimens. We
      conclude that performing 5 or 10 replicates considerably increased the
      sensitivity and reproducibility of C. pneumoniae PCR and enabled quantitation for
      clinical specimens. Due to sampling variability, PCR tests done without
      replication may miss a large proportion of positive specimens, particularly for
      specimens with small amounts of target C. pneumoniae DNA present.

PMID- 11325994
TI  - Molecular epidemiology of Mycobacterium tuberculosis in Norway.
AB  - The incidence of tuberculosis in Norway is one of the lowest in the world, and
      approximately half of the cases occur in first- and second-generation immigrants.
      In the present study, the genetic diversity of 92% of all strains of
      Mycobacterium tuberculosis isolated in Norway in 1994 to 1998 was assessed using
      restriction fragment length polymorphism (RFLP) analysis, with the insertion
      sequence IS6110 and the repetitive element DR as probes, to determine the degree
      of active transmission between patients. The DR probe was used as a secondary
      molecular marker to support or rule out clustering of strains with fewer than
      five copies of IS6110. After exclusion of 20 cultures representing laboratory
      contamination, 573 different IS6110 patterns were found among the 698 strains
      analyzed. Of these 573 patterns, 542 were observed only once and 31 were shared
      by 2 to 14 isolates. Among 81 strains (11.5%) carrying fewer than five copies of
      IS6110, 56 RFLP patterns were found when the results of both the IS6110 and DR
      methods were combined. Among the 698 strains, 570 were considered to be
      independent cases. A total of 14.5% of the native Norwegians and 19.7% of the
      foreign patients were part of a cluster. Thus, the degree of recent transmission
      of tuberculosis in Norway is low and the great majority of the cases are due to
      reactivation of previous disease. Transmission between immigrants and native
      Norwegians is uncommon. Two outbreaks, one among native Norwegians and one mainly
      among immigrants, have been ongoing for several years, indicating that, even in a
      low-incidence country such as Norway, with a good national program for
      tuberculosis surveillance, certain transmission chains are difficult to break.

PMID- 11325995
TI  - Sensitivity and specificity of human immunodeficiency virus rapid serologic
      assays and testing algorithms in an antenatal clinic in Abidjan, Ivory Coast.
AB  - To evaluate serologic testing algorithms for human immunodeficiency virus (HIV)
      based on a combination of rapid assays among persons with HIV-1 (non-B subtypes)
      infection, HIV-2 infection, and HIV-1-HIV-2 dual infections in Abidjan, Ivory
      Coast, a total of 1,216 sera with known HIV serologic status were used to
      evaluate the sensitivity and specificity of four rapid assays: Determine HIV-1/2,
      Capillus HIV-1/HIV-2, HIV-SPOT, and Genie II HIV-1/HIV-2. Two serum panels
      obtained from patients recently infected with HIV-1 subtypes B and non-B were
      also included. Based on sensitivity and specificity, three of the four rapid
      assays were evaluated prospectively in parallel (serum samples tested by two
      simultaneous rapid assays) and serial (serum samples tested by two consecutive
      rapid assays) testing algorithms. All assays were 100% sensitive, and
      specificities ranged from 99.4 to 100%. In the prospective evaluation, both the
      parallel and serial algorithms were 100% sensitive and specific. Our results
      suggest that rapid assays have high sensitivity and specificity and, when used in
      parallel or serial testing algorithms, yield results similar to those of enzyme
      linked immunosorbent assay-based testing strategies. HIV serodiagnosis based on
      rapid assays may be a valuable alternative in implementing HIV prevention and
      surveillance programs in areas where sophisticated laboratories are difficult to
      establish.

PMID- 11325996
TI  - Mutations in the rpoB gene of rifampin-resistant Mycobacterium tuberculosis
      isolates in Spain and their rapid detection by PCR-enzyme-linked immunosorbent
      assay.
AB  - Genetic alterations in the rpoB gene were characterized in 50 rifampin-resistant
      (Rif(r)) clinical isolates of Mycobacterium tuberculosis complex from Spain. A
      rapid PCR-enzyme-linked immunosorbent assay (ELISA) technique for the
      identification of rpoB mutations was evaluated with isolates of the M.
      tuberculosis complex and clinical specimens from tuberculosis patients that were
      positive for acid-fast bacilli (AFB). Sequence analysis demonstrated 11 different
      rpoB mutations among the Rif(r) isolates in the study. The most frequent
      mutations were those associated with codon 531 (24 of 50; 48%) and codon 526 (11
      of 50; 22%). Although the PCR-ELISA does not permit characterization of the
      specific Rif(r) allele within each strain, 10 of the 11 Rif(r) genotypes were
      correctly identified by this method. We used the PCR-ELISA to predict the
      rifampin susceptibility of M. tuberculosis complex organisms from 30 AFB-positive
      sputum specimens. For 28 samples, of which 9 contained Rif(r) organisms and 19
      contained susceptible strains, results were concordant with those based on
      culture-based drug susceptibility testing and sequencing. Results from the
      remaining two samples could not be interpreted because of low bacillary load
      (microscopy score of 1+ for 1 to 9 microorganisms/100 fields). Our results
      suggest that the PCR-ELISA is an easy technique to implement and could be used as
      a rapid procedure for detecting rifampin resistance to complement conventional
      culture-based methods.

PMID- 11325997
TI  - Assignment of CDC weak oxidizer group 2 (WO-2) to the genus Pandoraea and
      characterization of three new Pandoraea genomospecies.
AB  - CDC weak oxidizer group 2 (WO-2) consists of nine phenotypically similar human
      clinical isolates received by the Centers for Disease Control and Prevention
      between 1989 and 1998. Four of the isolates were from blood, three were from
      sputum, and one each was from bronchial fluid and maxillary sinus. All are
      aerobic nonfermentative, motile gram-negative rods with one to eight polar
      flagella per cell. All grew at 25 and 35 degrees C and were positive for
      catalase, urease (usually delayed 3 to 7 days), citrate, alkalinization of litmus
      milk, oxidization of glycerol (weakly), and growth on MacConkey agar and in
      nutrient broth without NaCl. All except one strain were oxidase positive with the
      Kovacs method, and all except one isolate weakly oxidized D-glucose. All were
      negative for oxidation of D-xylose, D-mannitol, lactose, sucrose, maltose, and 20
      other carbohydrates, esculin hydrolysis, indole production, arginine dihydrolase,
      and lysine and ornithine decarboxylase. Only two of nine isolates reduced
      nitrate. Broth microdilution susceptibilities were determined for all strains
      against 13 antimicrobial agents. Most of the strains were resistant to
      ampicillin, extended-spectrum cephalosporins, and aminoglycosides, including
      gentamicin, tobramycin, and amikacin, but they varied in their susceptibility to
      fluoroquinolones. High-performance liquid chromatographic and mass spectrometric
      analyses of the WO-2 group identified ubiquinone-8 as the major quinone
      component. The percent G+C of the WO-2 strains ranged from 65.2 to 70.7% (thermal
      denaturation method). All shared a common cellular fatty acid (CFA) profile,
      which was characterized by relatively large amounts (7 to 22%) of 16:1omega7c,
      16:0, 17:0cyc, 18:1omega7c, and 19:0cyc(11-12); small amounts (1 to 3%) of 12:0
      and 14:0; and eight hydroxy acids, 2-OH-12:0 (4%), 2-OH-14:0 (trace), 3-OH-14:0
      (12%), 2-OH-16:1 (1%), 2-OH-16:0 (3%), 3-OH-16:0 (4%), 2-OH-18:1 (2%), and 2-OH
      19:0cyc (3%). This profile is similar to the CFA profile of Pandoraea, a recently
      described genus associated with respiratory infections in cystic fibrosis
      patients (T. Coenye et al., Int. J. Syst. Evol. Microbiol., 50:887-899, 2000).
      Sequencing of the 16S rRNA gene (1,300 bp) for all nine strains indicated a high
      level (> or =98.8%) of homogeneity with Pandoraea spp. type strains. DNA-DNA
      hybridization analysis (hydroxyapatite method; 70 degrees C) confirmed the
      identity of WO-2 with the genus Pandoraea and assigned three strains to Pandoraea
      apista and three to Pandoraea pnomenusa, and identified three additional new
      genomospecies containing one strain each (ATCC BAA-108, ATCC BAA-109, ATCC BAA
      110). This study also shows that Pandoraea isolates may be encountered in blood
      cultures from patients without cystic fibrosis.

PMID- 11325999
TI  - Clustering of South African Helicobacter pylori isolates from peptic ulcer
      disease patients is demonstrated by repetitive extragenic palindromic-PCR
      fingerprinting.
AB  - The present report assesses the association between clonal groupings, disease,
      and the virulence fingerprint of 76 South African Helicobacter pylori cagA(+)
      strains isolated from 57 Cape-colored subjects. Two methods, repetitive
      extragenic palindromic (REP)-PCR and random amplified polymorphic DNA (RAPD)-PCR,
      were used to generate DNA fingerprints, and computer-assisted analysis was used
      to derive clusters. The two PCR techniques were only partially complementary
      (48%). REP-PCR fingerprints identified a distinct pathological cluster consisting
      of strains from 63% of the patients and was strongly associated with both disease
      (P < 0.00001) and the vacuolating cytotoxin A (vacA) signal sequence type (P <
      0.003). RAPD-PCR fingerprinting was not associated with disease and was less
      strongly associated with vacA (P < 0.05) than REP-PCR was. Hierarchical analysis
      indicated that isolates from patients with peptic ulcer disease tended to cluster
      differently than isolates from patients with gastritis alone or gastric
      adenocarcinoma. These relationships are consistent with a loosely clonal
      population structure associated with disease for H. pylori in the Cape-colored
      population in South Africa.

PMID- 11325998
TI  - Persistence of two invasive Streptococcus pneumoniae clones of serotypes 1 and 5
      in comparison to that of multiple clones of serotypes 6B and 23F among children
      in southern Israel.
AB  - We conducted a study to examine the clonal distribution of invasive serotype 1
      and 5 isolates as representatives of serotypes that are rarely carried by healthy
      individuals compared to that of invasive serotype 6B and 23F isolates as
      representatives of serotypes often carried by young children for prolonged
      periods. All invasive serotype 1, 5, 6B, and 23F isolates recovered from blood
      cultures during January 1995 to May 1999 were analyzed; these included 66
      serotype 1, 30 serotype 5, 11 serotype 6B, and 15 serotype 23F isolates. One
      hundred thirty-three nasopharyngeal (NP) isolates of the indicated four serotypes
      from healthy children were also studied. The strains were characterized using
      serotyping, antimicrobial susceptibility testing, and pulsed-field gel
      electrophoresis profiling. We found that both invasive and NP serotype 1 and 5
      isolates were susceptible to penicillin and that each serotype showed only one
      clonal type. In contrast, serotype 6B and 23F strains showed different phenotypic
      characteristics as well as multiple clonal types; 10 clones were identified among
      6B isolates, and 11 clones were identified among 23F isolates.

PMID- 11326001
TI  - Adaptation of Escherichia coli to the bovine mammary gland.
AB  - Clinical mastitis in six Somerset dairy herds was monitored over a 12-month
      period. Escherichia coli was implicated in 34.7% of all clinical cases. Forty-one
      percent of all clinical E. coli mastitis cases occurred in just 2.2% of the
      population. A total of 23.9% of clinical E. coli cases occurred in quarters
      suffering recurrent cases of E. coli mastitis. The genotypes of strains involved
      in recurrent cases of clinical E. coli mastitis were compared by DNA
      fingerprinting with enterobacterial repetitive intergenic consensus primers. In
      85.7% of cases of recurrent quarter E. coli mastitis, the same genotype was
      implicated as the cause of disease, suggesting persistence of the organism within
      the mammary environment. The same genotype as that in the original case was also
      implicated in 8.5% of recurrent cases occurring in different quarters of the same
      cow, suggesting spread between quarters. These findings challenge our current
      understanding of the epidemiology of E. coli mastitis and suggest that pathogen
      adaptation and host susceptibility may be playing a part in the changing pattern
      of clinical mastitis experienced in the modern dairy herd.

PMID- 11326000
TI  - Simple method for determining biovar and serovar types of Ureaplasma urealyticum
      clinical isolates using PCR-single-strand conformation polymorphism analysis.
AB  - Ureaplasma urealyticum has been associated with urethritis in men, obstetric
      problems in women, and respiratory distress syndrome in preterm infants. U.
      urealyticum can be divided into two biovars comprising 14 serovars. Partial
      sequences of genes encoding the multiple-banded antigens of the cell surface are
      known. Using a commercially available precast DNA mutation detection gel system,
      we have developed a simple and reproducible PCR-single-strand conformation
      polymorphism analysis method for differentiating the biovars of this species that
      reveals five patterns among the 14 serovars and enables clinical isolates to be
      typed directly from broth cultures.

PMID- 11326002
TI  - Prevalence of human immunodeficiency virus type 1 (HIV-1) non-B subtypes in
      foreigners living in Madrid, Spain, and comparison of the performances of the
      AMPLICOR HIV-1 MONITOR version 1.0 and the new automated version 1.5.
AB  - Plasma specimens collected in 1999 from 32 human immunodeficiency virus type 1
      (HIV-1)-infected foreigners living in Madrid, Spain, were examined for the
      presence of non-B subtypes. Furthermore, plasma viremia was quantified using two
      different AMPLICOR HIV-1 MONITOR tests, version 1.0 and the new upgraded and
      automated version 1.5 (COBAS). Most patients came from Africa, where they most
      likely had acquired HIV-1 infection through sexual contact. HIV-1 genetic
      subtyping was based on the phylogenetic analysis of the protease gene. Twenty-two
      subtype B, six subtype G, two subtype C, one subtype A, and one D subtype
      infection were found. Overall, non-B subtypes represented 31.25% of the study
      population. Irrespective of the HIV-1 variant, viral load values above the
      detection limit (200 HIV RNA copies/ml) increased from 56.2 to 71.9% for results
      obtained using MONITOR version 1.0 and COBAS, respectively. Moreover, significant
      differences in viral load values (>0.5 logs) were recognized in up to 37.5% of
      samples. In summary, COBAS seemed to be more reliable for testing plasma viral
      load in HIV-infected immigrants living in Spain, one third of whom carried non-B
      subtypes.

PMID- 11326003
TI  - Evaluation of biosite triage Clostridium difficile panel for rapid detection of
      Clostridium difficile in stool samples.
AB  - One hundred two stool samples were tested by both the rapid Triage Clostridium
      difficile Panel (Triage Panel) and the cytotoxin cell culture assay. Five samples
      positive by both the C. difficile toxin A (Tox A) and common antigen components
      of the Triage Panel had cytotoxin titers of > or =10,000. Twenty-three samples
      were Triage Panel Tox A negative but common antigen positive. Ten of these had
      cytotoxin titers of 10 to 1,000, but 13 were cytotoxin negative. Bacterial
      isolates obtained from 8 of these 13 specimens were analyzed for Tox A and B
      genes by PCR, and only two contained toxigenic bacteria. Thus, the majority of
      samples positive only for C. difficile common antigen contained nontoxigenic
      bacteria. A Triage Panel Tox A-positive result indicated a sensitivity,
      specificity, positive predictive value (PPV), and negative predictive value (NPV)
      of 33.3, 100, 100, and 88.2%, respectively. A Triage Panel common antigen
      positive result indicated a sensitivity, specificity, PPV, and NPV of 100, 82.7,
      53.6, and 100%, respectively. The high NPV of the Triage Panel common antigen,
      together with rapid reporting of results, should prove useful in avoiding
      unnecessary use of contact precautions and antibiotic treatment for C. difficile
      negative patients. However, with Triage Panel common antigen-positive patients, a
      sensitive cytotoxin assay should be used to distinguish true cytotoxin-positive
      patients from C. difficile carriers.

PMID- 11326004
TI  - Chlamydia pneumoniae serology: importance of methodology in patients with
      coronary heart disease and healthy individuals.
AB  - Most publications on the relationship between infection with Chlamydia pneumoniae
      and coronary heart disease (CHD) propose an association, but negative studies are
      also reported. Seroepidemiological studies vary in the use of different
      serological methods, different cutoff limits, different sampling times in
      relation to acute cardiac events, and different clinical stages of CHD. We wanted
      to compare three different commercially available methods for measuring Chlamydia
      antibodies to see how the choice of method influenced the prevalence of
      seropositive individuals in CHD patients and in healthy individuals and to see if
      sampling time in relation to an acute cardiac event or the stage of
      atherothrombotic disease influenced the results. Blood samples from 197 CHD
      patients and 197 individually matched healthy control individuals were tested at
      baseline and after 6 months; the mean age was 55 years in both groups, and 18%
      were women. Among the CHD patients, 166 were included at a median of 16 days
      after an acute cardiac event and 31 had chronic disease with the latest acute
      event being >3 months earlier. The difference in prevalence of antibodies between
      the CHD patients and the healthy controls was significant when Chlamydia
      lipopolysaccharide antibodies were measured, while no significant differences
      between the study groups were observed by the two methods detecting Chlamydia
      pneumoniae major outer membrane protein antibodies. The number of seropositive
      individuals was quite similar at inclusion and 6 months later, and no significant
      differences were observed between patients with a recent cardiac event and those
      with a more remote cardiac event. We conclude that the choice of serological
      method is of major importance when evaluating a possible relationship between C.
      pneumoniae and CHD.

PMID- 11326005
TI  - Dynamics of a nosocomial outbreak of multidrug-resistant Pseudomonas aeruginosa
      producing the PER-1 extended-spectrum beta-lactamase.
AB  - From November 1998 to August 1999, a large outbreak occurred in the general
      intensive care unit of the Ospedale di Circolo in Varese (Italy), caused by
      Pseudomonas aeruginosa producing the PER-1 extended-spectrum beta-lactamase. A
      total of 108 clinical isolates of P. aeruginosa resistant to broad-spectrum
      cephalosporins were recovered from 18 patients. Epidemic isolates were
      characterized by synergy between clavulanic acid and ceftazidime, cefepime, and
      aztreonam. Isoelectric focusing of crude bacterial extracts detected two
      nitrocefin-positive bands with pI values of 8.0 and 5.3. PCR amplification and
      characterization of the amplicons by restriction analysis and direct sequencing
      indicated that the epidemic isolates carried a bla(PER-1) determinant. The
      outbreak was of clonal origin as shown by pulsed-field gel electrophoresis
      analysis. This technique also indicated that the epidemic strain was not related
      to three other PER-1-positive isolates obtained at the same hospital in 1997.
      Typing by enterobacterial repetitive intergenic consensus-PCR showed that minor
      genetic variations occurred during the outbreak. The epidemic strain was
      characterized by a multiple-drug-resistance phenotype that remained unchanged
      over the outbreak, including extended-spectrum cephalosporins, monobactams,
      aminoglycosides, and fluoroquinolones. Isolation of infected patients and
      appropriate carbapenem therapy were successful in ending the outbreak. Our report
      indicates that the bla(PER-1) resistance determinant may become an emerging
      therapeutic problem in Europe.

PMID- 11326006
TI  - Detection of salmonellae in chicken feces by a combination of tetrathionate broth
      enrichment, capillary PCR, and capillary gel electrophoresis.
AB  - This report describes a rapid detection procedure for salmonellae from chicken
      feces by the combination of tetrathionate primary enrichment (preenrichment [PE])
      bacterial lysis-capillary PCR and capillary gel electrophoresis. Pure Salmonella
      enterica serovar Enteritidis 64K was reisolated and detected by capillary PCR
      after buffered peptone water and nutrient broth, tetrathionate broth base Hajna
      (TTBH), and tetrathionate broth (TTB) preenrichments. When the same culture was
      mixed with intestinal homogenate, bacteriological reisolation and capillary PCR
      detection was achieved only by TTBH and TTB preenrichments. Capillary gel
      electrophoresis revealed that a Salmonella genus-specific 281-bp PCR product was
      detected when Salmonella strains but not non-Salmonella strains were tested. The
      detection limit of capillary PCR with whole-cell DNA extracted from pure
      Salmonella enterica serovars Enteritidis 64K, Typhimurium LT2-CIP60-62, and
      Gallinarum 64K was 3, 3, and 9 CFU ml(-1), respectively. The detection limit of
      capillary PCR from whole-cell DNA extracted from intestinal homogenate
      artificially contaminated with the same three strains was 3, 3, and 7 CFU ml(-1),
      respectively. We compared the results of the capillary PCR and bacteriological
      examination from the natural samples. Thirty-five of 53 naturally contaminated
      samples produced a specific PCR product. In 9 of the 35 PCR-positive samples,
      Salmonella could not be detected bacteriologically either by PE or a primary and
      delayed secondary enrichment (DSE) combination. In the 18 PCR-negative samples, 4
      samples were found to harbor Salmonella by both PE and DSE and 14 samples were
      positive after DSE. Fifty-three additional intestinal homogenate samples, which
      were negative by their PE and DSE in bacteriological examination, were found to
      be also negative by their PCRs. The total time required to detect Salmonella with
      the capillary PCR method we used was approximately 20 h. If samples are from
      clinically diseased birds, the total time for PCR and detection is reduced to 2 h
      since the 18-h PE is not required. These results indicate that TTB enrichment,
      bacterial lysis, and genus-specific capillary PCR combined with capillary gel
      electrophoresis constitute a sensitive and selective procedure which has the
      potential to rapidly identify Salmonella-infected flocks.

PMID- 11326007
TI  - Monoclonal antibody-based competitive enzyme-linked immunosorbent assay for
      detection of morbillivirus antibody in marine mammal sera.
AB  - A competitive enzyme-linked immunosorbent assay (cELISA), using two monoclonal
      antibodies (MAbs), was developed and compared with the standard virus
      neutralization test (VNT) for detecting antibodies against canine distemper virus
      (CDV) and phocine distemper virus (PDV) in sera from dogs and various species of
      marine mammals. The test depends on the blocking of MAb binding to solid-phase
      antigen in the presence of positive serum. Test conditions were optimized by
      using control VNT-negative and -positive sera specific for CDV and PDV. A
      positive cutoff value of 30% inhibition, which represents the mean cutoff of a
      VNT-negative population (n = 623) plus 2 standard deviations, was adopted for the
      test. A total of 736 serum samples were tested by the new cELISA and by the VNT
      as the "gold standard." An unexpected but useful finding was the ability of this
      CDV- and PDV-specific cELISA to also detect antibodies against the related pair
      dolphin morbillivirus and porpoise morbillivirus. Based on a subpopulation of 625
      sera used in statistical analyses, the overall sensitivity and specificity of
      cELISA relative to those of the VNT were 94.9 and 97.7%, respectively. Because
      the cELISA proved to be nearly as sensitive and specific as the VNT while being
      simpler and more rapid, it would be an adequate screening test for suspect CDV or
      PDV cases and would also be useful for epidemiological surveillance of
      morbilliviral infections in marine mammal populations.

PMID- 11326008
TI  - Molecular variability of the adhesin-encoding gene pvpA among Mycoplasma
      gallisepticum strains and its application in diagnosis.
AB  - Mycoplasma gallisepticum is an important pathogen of chickens and turkeys that
      causes considerable economic losses to the poultry industry worldwide. The
      reemergence of M. gallisepticum outbreaks among poultry, the increased use of
      live M. gallisepticum vaccines, and the detection of M. gallisepticum in game and
      free-flying song birds has strengthened the need for molecular diagnostic and
      strain differentiation tests. Molecular techniques, including restriction
      fragment length polymorphism of genomic DNA (RFLP) and PCR-based random
      amplification of polymorphic DNA (RAPD), have already been utilized as powerful
      tools to detect intraspecies variation. However, certain intrinsic drawbacks
      constrain the application of these methods. The main goal of this study was to
      determine the feasibility of using an M. gallisepticum-specific gene encoding a
      phase-variable putative adhesin protein (PvpA) as the target for molecular
      typing. This was accomplished using a pvpA PCR-RFLP assay. Size variations among
      PCR products and nucleotide divergence of the C-terminus-encoding region of the
      pvpA gene were the basis for strain differentiation. This method can be used for
      rapid differentiation of vaccine strains from field isolates by amplification
      directly from clinical samples without the need for isolation by culture.
      Moreover, molecular epidemiology of M. gallisepticum outbreaks can be performed
      using RFLP and/or sequence analysis of the pvpA gene.

PMID- 11326009
TI  - Rapid pulsed-field gel electrophoresis protocol for subtyping of Campylobacter
      jejuni.
AB  - We developed a rapid pulsed-field gel electrophoresis (PFGE) protocol for
      subtyping Campylobacter isolates based on the standardized protocols used by
      PulseNet laboratories for the subtyping of other food-borne bacterial pathogens.
      Various combinations of buffers, reagents, reaction conditions (e.g., cell
      suspension concentration, lysis time, lysis temperature, and restriction enzyme
      concentration), and electrophoretic parameters were evaluated in an effort to
      devise a protocol that is simple, rapid, and robust. PFGE analysis of
      Campylobacter isolates can be completed in 24 to 30 h using this protocol,
      whereas the most widely used current protocols require 3 to 4 days to complete.
      Comparison of PFGE patterns obtained in six laboratories showed that subtyping
      results obtained using this protocol are highly reproducible.

PMID- 11326010
TI  - One-tube real-time isothermal amplification assay to identify and distinguish
      human immunodeficiency virus type 1 subtypes A, B, and C and circulating
      recombinant forms AE and AG.
AB  - To halt the human immunodeficiency virus type 1 (HIV-1) epidemic requires
      interventions that can prevent transmission of numerous HIV-1 subtypes. The most
      frequently transmitted viruses belong to the subtypes A, B, and C and the
      circulating recombinant forms (CRFs) AE and AG. A fast one-tube assay that
      identifies and distinguishes among subtypes A, B, and C and CRFs AE and AG of HIV
      1 was developed. The assay amplifies a part of the gag gene sequence of the
      genome of all currently known HIV-1 subtypes and can identify and distinguish
      among the targeted subtypes as the reaction proceeds, because of the addition of
      subtype-specific molecular beacons with multiple fluorophores. The combination of
      isothermal nucleic acid sequence-based amplification and molecular beacons is a
      new approach in the design of real-time assays. To obtain a sufficiently specific
      assay, we developed a new strategy in the design of molecular beacons, purposely
      introducing mismatches in the molecular beacons. The subtype A and CRF AG
      isolates reacted with the same molecular beacon. We tested the specificity and
      sensitivity of the assay on a panel of the culture supernatant of 34 viruses
      encompassing all HIV-1 subtypes: subtypes A through G, CRF AE and AG, a group O
      isolate, and a group N isolate. Assay sensitivity on this panel was 92%, with 89%
      correct subtype identification relative to sequence analysis. A linear
      relationship was found between the amount of input RNA in the reaction mixture
      and the time that the reaction became positive. The lower detection level of the
      assay was approximately 10(3) copies of HIV-1 RNA per reaction. In 38% of 50
      serum samples from HIV-1-infected individuals with a detectable amount of virus,
      we could identify subtype sequences with a specificity of 94% by using sequencing
      and phylogenetic analysis as the "gold standard." In conclusion, we showed the
      feasibility of the approach of using multiple molecular beacons labeled with
      different fluorophores in combination with isothermal amplification to identify
      and distinguish subtypes A, B, and C and CRFs AE and AG of HIV-1. Because of the
      low sensitivity, the assay in this format would not be suited for clinical use
      but can possibly be used for epidemiological monitoring as well as vaccine
      research studies.

PMID- 11326012
TI  - Prevalence of congenital Toxoplasma gondii infection among newborns from the
      Poznan region of Poland: validation of a new combined enzyme immunoassay for
      Toxoplasma gondii-specific immunoglobulin A and immunoglobulin M antibodies.
AB  - We determined the value of a new serological assay detecting Toxoplasma-specific
      immunoglobulin M (IgM) and IgA antibodies at birth for use in mass neonatal
      screening. The incidence of congenital infection in newborns was compared with
      data from an epidemiological investigation on the seroprevalence of Toxoplasma in
      the studied population. Peripheral blood was collected on Guthrie cards during
      the first 3 days of life and tested for anti-Toxoplasma IgA and IgM using a
      noncommercial immunocapture enzyme-linked immunosorbent assay (ELISA). When the
      screening assay was positive, serum samples from the child and the mother were
      collected for use in Western blotting comparative immunological profile analysis
      and traditional serological tests for determination of specific IgG, IgM, and IgA
      antibodies. From December 1998 to April 2000, 17,653 filter paper samples from
      live-born neonates were successively screened. Congenital T. gondii infection was
      finally confirmed in 19 newborns. In traditional assays, 13 of 19 infants were
      IgM and IgA positive using filter paper eluates at birth, 1 child was positive
      only for IgM, 1 patient was positive for IgM and borderline for IgA, 1 had an
      equivocal level of IgA, and 3 cases were confirmed only by the Western blot
      assay. The prevalence of Toxoplasma-specific IgA and/or IgM in filter paper
      samples at birth was 1 per 929 live-born neonates (1.08/1,000) or about 1 per 523
      children (1.9/1,000) born to nonimmune women with a potential risk of primary T.
      gondii infection during pregnancy, compared to the actual seropositivity rate of
      43.7%. The diagnostic sensitivity of the combined IgA-IgM ELISA using neonatal
      filter paper specimens was not more than 95%, the positive predictive value of
      the test was 82.6%, and the diagnostic specificity was calculated to be 99.9%.
      The combined IgA-IgM ELISA is a valuable method for the diagnosis of congenital
      toxoplasmosis at birth and fulfills criteria for neonatal screening programs. The
      method showed a good diagnostic sensitivity in neonates untreated prenatally who
      were born in an area of high seroprevalence of T. gondii infection.

PMID- 11326011
TI  - Use of subgenic 18S ribosomal DNA PCR and sequencing for genus and genotype
      identification of acanthamoebae from humans with keratitis and from sewage
      sludge.
AB  - This study identified subgenic PCR amplimers from 18S rDNA that were (i) highly
      specific for the genus Acanthamoeba, (ii) obtainable from all known genotypes,
      and (iii) useful for identification of individual genotypes. A 423- to 551-bp
      Acanthamoeba-specific amplimer ASA.S1 obtained with primers JDP1 and JDP2 was the
      most reliable for purposes i and ii. A variable region within this amplimer also
      identified genotype clusters, but purpose iii was best achieved with sequencing
      of the genotype-specific amplimer GTSA.B1. Because this amplimer could be
      obtained from any eukaryote, axenic Acanthamoeba cultures were required for its
      study. GTSA.B1, produced with primers CRN5 and 1137, extended between reference
      bp 1 and 1475. Genotypic identification relied on three segments: bp 178 to 355,
      705 to 926, and 1175 to 1379. ASA.S1 was obtained from single amoeba, from
      cultures of all known 18S rDNA genotypes, and from corneal scrapings of Scottish
      patients with suspected Acanthamoeba keratitis (AK). The AK PCR findings were
      consistent with culture results for 11 of 15 culture-positive specimens and
      detected Acanthamoeba in one of nine culture-negative specimens. ASA.S1 sequences
      were examined for 6 of the 11 culture-positive isolates and were most closely
      associated with genotypic cluster T3-T4-T11. A similar distance analysis using
      GTSA.B1 sequences identified nine South African AK-associated isolates as
      genotype T4 and three isolates from sewage sludge as genotype T5. Our results
      demonstrate the usefulness of 18S ribosomal DNA PCR amplimers ASA.S1 and GTSA.B1
      for Acanthamoeba-specific detection and reliable genotyping, respectively, and
      provide further evidence that T4 is the predominant genotype in AK.

PMID- 11326013
TI  - Comparison of two methods for serotyping Campylobacter spp.
AB  - Two serotyping schemes (Penner and Laboratory of Enteric Pathogens [LEP]) based
      on soluble heat-stable antigens were used to analyze 3,788 Campylobacter sp.
      isolates. A significant percentage (36.6%) was untypeable using LEP serotyping;
      greater cross-reaction was also observed. The relative discrimination
      capabilities of the techniques were similar. Penner serotyping fulfils more of
      the requisite criteria for typing methods.

PMID- 11326014
TI  - Comparison of flavivirus universal primer pairs and development of a rapid,
      highly sensitive heminested reverse transcription-PCR assay for detection of
      flaviviruses targeted to a conserved region of the NS5 gene sequences.
AB  - Arthropod-transmitted flaviviruses are responsible for considerable morbidity and
      mortality, causing severe encephalitic, hemorrhagic, and febrile illnesses in
      humans. Because there are no specific clinical symptoms for infection by a
      determined virus and because different arboviruses could be present in the same
      area, a genus diagnosis by PCR would be a useful first-line diagnostic method.
      The six published Flavivirus genus primer pairs localized in the NS1, NS3, NS5,
      and 3' NC regions were evaluated in terms of specificity and sensitivity with
      flaviviruses (including the main viruses pathogenic for humans) at a titer of
      10(5) 50% tissue culture infectious doses (TCID(50)s) ml(-1) with a common
      identification step by agarose gel electrophoresis. Only one NS5 primer pair
      allowed the detection of all tested flaviviruses with the sensitivity limit of
      10(5) TCID(50)s ml(-1). Using a heminested PCR with new primers designed in the
      same region after an alignment of 30 different flaviviruses, the sensitivity of
      reverse transcription-PCR was improved and allowed the detection of about 200
      infectious doses ml(-1) with all of the tick- and mosquito-borne flaviviruses
      tested. It was confirmed that the sequenced amplified products in the NS5 region
      allowed predictability of flavivirus species by dendrogram, including the New
      York 99 West Nile strain. This technique was successfully performed with a
      cerebrospinal fluid sample from a patient hospitalized with West Nile virus
      encephalitis.

PMID- 11326016
TI  - The common ovine Shiga toxin 2-containing Escherichia coli serotypes and human
      isolates of the same serotypes possess a Stx2d toxin type.
AB  - Shiga toxin 2 (Stx2) has been reported as the main Shiga toxin associated with
      human disease. In addition, the Stx2 toxin type can have a profound impact on the
      degree of tissue damage in animal models. We have characterized the stx(2)
      subtype of 168 Shiga toxin-producing Escherichia coli (STEC) isolates of which
      146 were derived from ovine sources (principally feces and meat) and 22 were
      isolated from humans. The ovine STEC isolates were of serotypes that have been
      shown to occur commonly in the gastrointestinal tract of healthy sheep. The major
      stx(2) subtype in the ovine isolates was shown to be stx(2d-Ount) (119 of 146
      [81.5%]) and was predominantly associated with serotypes O75:H(-)/H8/H40, O91:H(
      ), O123:H(-), O128:H2, and OR:H2. However, 17 of 18 (94.4%) ovine isolates of
      serotype O5:H(-) possessed a stx(2d-O111/OX3a) subtype. Furthermore, STEC
      isolates of serotypes commonly found in sheep and recovered from both clinical
      and nonclinical human infections also contained a stx(2d) (stx(2d
      Ount/O111/OX3a)) subtype. These studies suggest that a specific stx(2) subtype(s)
      associates with serotype and may have important epidemiological implications for
      tracing sources of E. coli during outbreaks of STEC-associated diseases in
      humans.

PMID- 11326015
TI  - Nationwide German multicenter study on the prevalence of antibiotic resistance in
      streptococcal blood isolates from neutropenic patients and comparative in vitro
      activities of quinupristin-dalfopristin and eight other antimicrobials.
AB  - In a prospective multicenter study (1996 to 1999), 156 episodes of bacteremic
      streptococcal infections of neutropenic patients were evaluated. Streptococcus
      oralis (26.3%), S. pneumoniae (26.3%), S. agalactiae (11.5%), S. mitis (9%), and
      S. pyogenes (5.8%) were the predominant species. Four strains (2.6%) were found
      to be intermediately resistant to penicillin. One strain (0.6%) was found to be
      highly resistant to penicillin (MIC, 8 mg/liter). Reduced susceptibility to
      penicillin was detected among S. oralis (14.6%), S. mitis (7.1%), and S.
      pneumoniae (4.9%) isolates but was not recorded among S. agalactiae and S.
      pyogenes. Resistance rates and intermediate resistance rates for other
      antimicrobials were as follows (all species): amoxicillin, 1.3 and 3.2%;
      erythromycin, 16 and 2.6%; clindamycin, 5.8 and 0%; ciprofloxacin, 1.9 and 7.7%.
      Quinupristin-dalfopristin showed good in vitro activity against most
      streptococcal isolates (MIC at which 50% of the isolates were inhibited
      [MIC(50)], 0.5 mg/liter; MIC(90), 1 mg/liter, MIC range, 0.25 to 4 mg/liter).

PMID- 11326017
TI  - Myxobolus sp., another opportunistic parasite in immunosuppressed patients?
AB  - During a study of intestinal parasitic infections in human immunodeficiency virus
      positive patients, a parasite belonging to the phylum Myxozoa, recently described
      from human samples, was identified in one sample. When this parasite was stained
      by the modified Ziehl-Neelsen staining method, the features of the spores were
      identified: they were pyriform in shape, had thick walls, and had one suture and
      two polar capsules, with each one having four or five coils. The suture and two
      polar capsules were observed with the chromotrope-modified stain. The number of
      stools passed was more than 30 per day, but oocysts of Isospora belli were also
      found. Upon reexamination of some formalin- or merthiolate-iodine-formaldehyde
      preserved samples an identical parasite was found in another sample from a
      patient presenting with diarrhea. Strongyloides stercoralis larvae and eggs of
      Hymenolepis nana and Ascaris lumbricoides were also found in this sample. Given
      that both patients were also infected with other pathogens that cause diarrhea,
      the possible pathogenic role of this parasite could not be established. The
      probable route of infection also could not be established.

PMID- 11326018
TI  - New tests for syphilis: rational design of a PCR method for detection of
      Treponema pallidum in clinical specimens using unique regions of the DNA
      polymerase I gene.
AB  - A sensitive and specific PCR method to detect Treponema pallidum in clinical
      specimens was developed. PCR primers were designed based on two unique features
      of the DNA polymerase I gene (polA). The first distinctive characteristic is that
      the region codes for a high cysteine content and has low homology with similar
      regions of DNA polymerase I gene from known microorganisms. The second unique
      feature is the presence of four insertions in the gene. PCR tests using primers
      designed on the basis these regions reacted with various pathogenic T. pallidum
      subspecies but did not react with nonpathogenic treponemal species or other
      spirochetes. An additional 59 species of bacteria and viruses, including those
      that cause genital ulcers, tested negative. This PCR method is extremely robust
      and sensitive. The detection limit is about 10 to 25 organisms when analyzed on
      gel. However, the analytic sensitivity can be increased by at least 1 log, to a
      detection limit of a single organism, when the ABI 310 Prism Genetic Analyzer is
      used to detect fluorescence-labeled amplicons. We further used this test in a
      clinical setting and compared the results with results from a previously reported
      multiplex-PCR test (for T. pallidum, Haemophilus ducreyi, and herpes simplex
      virus). We tested 112 genital ulcer specimens by the polA PCR, obtaining a
      sensitivity of 95.8% and a specificity of 95.7%. These results suggest that the
      polA PCR is applicable as a routine clinical diagnostic test for syphilis.

PMID- 11326020
TI  - Phaeohyphomycosis caused by Alternaria infectoria in a renal transplant
      recipient.
AB  - We report on a case of phaeohyphomycosis caused by Alternaria infectoria in a
      renal transplant recipient with pulmonary infiltrates and multiple skin lesions.
      Diagnosis was based on microscopy and culture of the skin lesions. Treatment
      consisted of a combination of surgical excision and systemic antifungal therapy,
      first with itraconazole and subsequently with liposomal amphotericin B, for 39
      days. At a 20-month follow-up visit, no recurrence of the skin lesions or the
      pulmonary infiltrates had occurred.

PMID- 11326019
TI  - One-step purification of Enterocytozoon bieneusi spores from human stools by
      immunoaffinity expanded-bed adsorption.
AB  - An original, reliable, and reproducible method for the purification of
      Enterocytozoon bieneusi spores from human stools is described. We recently
      reported the production of a species-specific monoclonal antibody (MAb) 6E52D9
      immunoglobulin G2a (IgG2a) raised against the exospore of E. bieneusi spore
      walls. The MAb was used as a ligand to develop an immunoaffinity matrix. The
      mouse IgG2a MAb was bound directly to a Streamline rProtein A adsorbent, used for
      expanded-bed adsorption of immunoglobulins, for optimal spatial orientation of
      the antibody and maximum binding efficiency of the antigen. The complex was then
      cross-linked covalently using dimethyl pimelimidate dihydrochloride. After
      incubation of the immunoaffinity matrix with filtered stool samples containing
      numerous E. bieneusi spores and before elution with 6 M guanidine HCl, the
      expansion of the adsorbent bed eliminated all the fecal contaminants. The
      presence of spores in the elution fractions was determined by an indirect
      immunofluorescence antibody test (IFAT). E. bieneusi spores were found in the
      elution fraction in all four experiments and were still highly antigenic as
      indicated by IFAT. Smears examined by light microscopy contained very clean
      spores with no fecal debris or background bacterial and fungal contaminants.
      However, spore recovery rates were relatively low: an average of 10(7) spores
      were purified per run. This technique for isolating E. bieneusi spores directly
      from human stool samples with a high degree of purity opens up new approaches for
      studying this parasite.

PMID- 11326021
TI  - Does blood of healthy subjects contain bacterial ribosomal DNA?
AB  - Real-time PCR methods with primers and a probe targeting conserved regions of the
      bacterial 16S ribosomal DNA (rDNA) revealed a larger amount of rDNA in blood
      specimens from healthy individuals than in matched reagent controls. However, the
      origins and identities of these blood-associated bacterial rDNA sequences remain
      obscure.

PMID- 11326022
TI  - Utility of paired BACTEC MYCO/F LYTIC blood culture vials for detection of
      bacteremia, mycobacteremia, and fungemia.
AB  - In previous bloodstream infection studies in Malawi, we inoculated blood from a
      single venesection into a single BACTEC MYCO/F LYTIC (MFL) vial. Inoculation of
      one vial, however, would be expected to reduce the sensitivity of bloodstream
      pathogen detection with MFL vials. To ascertain the degree of this loss of
      sensitivity, blood was drawn from each of 228 febrile, adult inpatients in Malawi
      and 5 ml of each blood sample was inoculated into each of two MFL vials. Of 228
      paired vials, 51 (22%) were both positive, 172 (75%) were both negative, and 5
      (3%) had discordant results. Bloodstream infection would have been detected in 11
      (92%) of 12 patients with mycobacteremia and 38 (92%) of 41 patients with
      bacteremia had only one MFL vial been inoculated. Our study shows that a second
      MFL vial does not significantly increase diagnostic sensitivity.

PMID- 11326023
TI  - Real-time PCR assay targeting IS481 of Bordetella pertussis and molecular basis
      for detecting Bordetella holmesii.
AB  - Detection of Bordetella holmesii by a real-time PCR assay targeting IS481 of
      Bordetella pertussis is reported. Sequencing of IS481-specific PCR products from
      B. pertussis and B. holmesii isolates revealed sequence homology. Restriction
      fragment length polymorphism demonstrated a low copy number of IS481-like
      sequences in B. holmesii. These results, and culture of B. holmesii from patients
      with cough, suggest that the specificity and predictive value of IS481-based PCR
      assays for pertussis may be compromised.

PMID- 11326024
TI  - Pretreatment with urea-hydrochloric acid enhances the isolation of Helicobacter
      pylori from contaminated specimens.
AB  - Human saliva seeded with H. pylori was incubated in urea-HCl and then cultured on
      nonselective media. Pretreatment with 0.06 N HCl-0.08 M urea for 5 min at 37
      degrees C resulted in reproducible isolation of H. pylori, even at low inocula (<
      or =10(2) CFU/ml of saliva), despite the presence of large numbers of
      contaminating organisms.

PMID- 11326025
TI  - Use of recommended laboratory testing methods among patients with tuberculosis in
      California.
AB  - This study assessed the extent to which laboratory methods recommended by the
      Centers for Disease Control and Prevention were used in tuberculosis testing of
      patients in California in 1998. While recommended methods were used for most
      patients, there was room for improvement by hospital and independent non-health
      maintenance organization laboratories.

PMID- 11326026
TI  - Comparison of sequence analysis and the INNO-LiPA HBV DR line probe assay for
      detection of lamivudine-resistant hepatitis B virus strains in patients under
      various clinical conditions.
AB  - A line probe assay (INNO-LiPA HBV DR) detecting drug-resistant hepatitis B virus
      (HBV) strains was evaluated. Results concordant with sequence analysis were
      obtained with 48 of 56 serum samples from HBV-infected patients undergoing
      lamivudine therapy. In eight cases, additional minor subpopulations could be
      identified by the line probe assay.

PMID- 11326027
TI  - Evaluation of an automated liquid-handling system (Tecan Genesis RSP 100) in the
      Abbott LCx assay for Chlamydia trachomatis.
AB  - The present study investigated the feasibility of automating the specimen
      pipetting component of sample preparation in the LCx Chlamydia assay (LCx-CT
      assay; Abbott Laboratories, Chicago, Ill.) by using a commercially available
      liquid-handling system (Tecan Genesis RSP100; Tecan Inc., Research Triangle Park,
      N.C.). The Tecan instrument proved to be comparable in both precision and
      accuracy to a manual multipipettor (Eppendorf model 4850; Eppendorf Scientific,
      Westbury, N.Y.). The Tecan instrument was extensively checked for evidence of
      specimen-to-specimen transfer, and no level of contamination sufficient to
      generate a signal above the background in the LCx-CT assay was detected. Finally,
      pipetting speed was significantly improved by using the Tecan instrument. A mean
      time of 2.5 min was required to pipette a complete LCx-CT assay carousel (20
      samples and 4 controls) with the Tecan instrument, whereas 8.4 min was required
      to pipette a comparable number of samples manually (P < 0.001).

PMID- 11326028
TI  - Evaluation of clarithromycin resistance and cagA and vacA genotyping of
      Helicobacter pylori strains from the west of Ireland using line probe assays.
AB  - The prevalence of clarithromycin resistance-associated mutations, the cytotoxin
      associated gene (cagA), and the various vacuolating cytotoxin (vacA) genotypes
      was determined in 50 gastric biopsy specimens from Helicobacter pylori-infected
      patients, using line probe assays. The clarithromycin resistance-associated
      mutation A2143G was detected in H. pylori strains from 26% of the specimens,
      which suggested that the high rate of H. pylori treatment failure in Ireland may
      be partly attributable to the presence of these mutations. All strains examined
      carried the vacA s1 genotype, and 76% were cagA positive. Of these 50 specimens,
      13 (26%) carried H. pylori strains with vacA midregion genotype m1, 29 (58%)
      carried strains that were m2, 1 (2%) was infected by a strain that was positive
      for both m1 and m2, and 7 (14%) carried strains that could not be typed.

PMID- 11326029
TI  - Rotavirus G and P genotypes in rural Ghana.
AB  - An epidemiological study of rotavirus infection was conducted on specimens
      collected from patients with gastroenteritis and domiciled in the rural Upper
      Eastern Region of Ghana during 1998. Fifty isolates, randomly selected from 165
      human group A rotavirus-positive samples, were G and P characterized by a reverse
      transcription (RT)-PCR assay using a seminested multiplex method. Rotaviruses of
      the G3 genotype were found to be the predominant strain (78%), followed by G2
      (14%) and G1 (2%). Mixed infections, as shown by combinations of G3 and G2 (4%)
      and G3 and G1 (2%), were also observed. P typing showed P[4] (72.34%) to be the
      prevalent strain, followed by P[6] (21.3%), P[8] (2.13%), and a combination of
      P[4] and P[6] (4.3%).

PMID- 11326030
TI  - Evidence of in vivo transfer of a plasmid encoding the extended-spectrum beta
      lactamase TEM-24 and other resistance factors among different members of the
      family Enterobacteriaceae.
AB  - The epidemiological study of several multidrug-resistant Enterobacteriaceae
      isolated from five patients demonstrated in vivo dissemination of a 100-kb
      plasmid encoding the extended-spectrum beta-lactamase TEM-24 from a clonal strain
      of Enterobacter aerogenes to different strains of Klebsiella pneumoniae,
      Escherichia coli, Proteus vulgaris, Proteus mirabilis, and Serratia marcescens.

PMID- 11326031
TI  - Phylogenetic characterization of genotype 4 hepatitis C virus isolates from
      Argentina.
AB  - Among 114 patients infected with hepatitis C virus, three genotype 4 isolates,
      unusual in Argentina, were detected by phylogenetic analysis over different
      genomic regions. The patients were not related. One sample was associated with
      Egyptian sequences, and the others were associated with a Zairean isolate, a fact
      which reinforces the idea that they are from independent sources.

PMID- 11326032
TI  - Use of the Gen-Probe amplified mycobacterium tuberculosis direct test for early
      detection of Mycobacterium tuberculosis in BACTEC 12B medium.
AB  - To achieve better sensitivity than direct testing and better turnaround time than
      current culture and identification methods, the Gen-Probe Mycobacterium
      Tuberculosis Direct method was used to detect Mycobacterium tuberculosis in
      BACTEC 12B medium cultures when they first gave a growth index (GI) of at least
      10 (MTD/BACTEC method). Of 179 acid-fast, smear-positive specimens that were
      culture positive for M. tuberculosis, all were positive by the MTD/BACTEC method
      (sensitivity, 100%). Positive results were obtained only with tuberculosis
      patients. For diagnostic specimens from untreated patients, the mean time to
      achieve a GI of 10 was 6 days.

PMID- 11326033
TI  - Laboratory diagnosis of Clostridium difficile-associated diarrhea and colitis:
      usefulness of Premier Cytoclone A+B enzyme immunoassay for combined detection of
      stool toxins and toxigenic C. difficile strains.
AB  - Detection of Clostridium difficile toxins A and B in stools by Premier Cytoclone
      A+B enzyme immunoassay (EIA) was compared with detection by stool culture for C.
      difficile followed by detection of toxigenic isolates using the same EIA. Chart
      reviews were performed to evaluate the likelihood of C. difficile-associated
      diarrhea and colitis (CADC) for all patients with at least one positive toxin
      assay. While the toxins were detected in 58 of 85 consecutive CADC patients by
      both assays, CADC in 5 patients was detected only by stool toxin assay, and in 22
      patients CADC was detected only by toxigenic culture. Our results suggest that
      for laboratories using a rapid toxin A+B EIA, direct toxin detection in stools
      should be combined with toxigenic culture in cases in which there is a negative
      stool toxin assay.

PMID- 11326034
TI  - Rotavirus genotypes P[4]G9, P[6]G9, and P[8]G9 in hospitalized children with
      acute gastroenteritis in Rio de Janeiro, Brazil.
AB  - Fifty-three rotavirus-positive fecal specimens from children with diarrhea
      admitted to a Rio de Janeiro, Brazil, children's hospital between January 1997
      and December 1998 were characterized for P and G types by using reverse
      transcription-PCR. Genotype P[4]G2 accounted for 21% of isolates, while uncommon
      genotypes P[8]G9, P[6]G9, and P[4]G9 accounted for 13% of the isolates.

PMID- 11326035
TI  - Identification of Actinobacillus actinomycetemcomitans serotypes by multiplex
      PCR.
AB  - Oligonucleotide primers specific for gene clusters involved in the biosynthesis
      of serotype-specific polysaccharide antigens were designed to identify
      Actinobacillus actinomycetemcomitans serotypes a to e using the multiplex PCR.
      This method may be useful for serotype-specific genotyping rapidly and directly
      from clinical samples containing various organisms.

PMID- 11326036
TI  - Evaluation of PCR using TRC(4) and IS6110 primers in detection of tuberculous
      meningitis.
AB  - We have evaluated a new set of primers (TRC(4)) in comparison with the IS6110
      primers commonly used in PCR to detect tuberculous meningitis among children. The
      levels of concordance between the results of IS6110 PCR and TRC(4) PCR with
      cerebrospinal fluid specimens from patients with clinically confirmed tuberculous
      meningitis were 80 and 86%, respectively. Results with the two primer sets were
      concordant for 55 positive and 22 negative specimens (n = 98). We conclude that
      the sensitivity of PCR can be increased by using both IS6110 and TRC(4) primers.

PMID- 11326037
TI  - Variable oncogene promoter activity of human papillomavirus type 16 cervical
      cancer isolates from Australia.
AB  - The functional significance of sequence variation within the upstream regulatory
      region (URR) of six human papillomavirus type 16 (HPV16) cervical cancer isolates
      from Australia was investigated. Specific changes in transcription factor binding
      sites leading to increased promoter activity may explain the transforming ability
      of some episomal HPV16 isolates.

PMID- 11326038
TI  - Evaluation of a reformulated CHROMagar Candida.
AB  - CHROMagar Candida is a differential culture medium for the isolation and
      presumptive identification of clinically important yeasts. Recently the medium
      was reformulated by Becton Dickinson. This study was designed to evaluate the
      performance of the new formula of CHROMagar against the original CHROMagar
      Candida for recovery, growth, and colony color with stock cultures and with
      direct plating of clinical specimens. A total of 90 stock yeast isolates
      representing nine yeast species, including Candida dubliniensis, as well as 522
      clinical specimens were included in this study. No major differences were noted
      in growth rate or colony size between the two media for most of the species.
      However, all 10 Candida albicans isolates evaluated consistently gave a lighter
      shade of green on the new CHROMagar formulation. In contrast, all 26 C.
      dubliniensis isolates gave the same typical dark green color on both media. A
      total of 173 of the 522 clinical specimens were positive for yeast, with eight
      yeast species recovered. The recovery rates for each species were equivalent on
      both media, with no consistent species-associated differences in colony size or
      color. Although both media were comparable in performance, the lighter green
      colonies of C. albicans isolates on the new CHROMagar made it easier to
      differentiate between C. albicans and C. dubliniensis isolates. In conclusion,
      the newly formulated Becton Dickinson CHROMagar Candida medium is as equally
      suited as a differential medium for the presumptive identification of yeast
      species and for the detection of multiple yeast species in clinical specimens as
      the original CHROMagar Candida medium.

PMID- 11326039
TI  - Virulence properties and serotypes of Shiga toxin-producing Escherichia coli from
      healthy Australian slaughter-age sheep.
AB  - A group of 1,623 ovine fecal samples recovered from 65 geographically distinct
      mutton sheep and prime lamb properties across New South Wales, Australia, were
      screened for the presence of Shiga toxin-producing Escherichia coli (STEC)
      virulence factors (stx(1), stx(2), eaeA, and ehxA). A subset was cultured for
      STEC isolates containing associated virulence factors (eaeA and/or ehxA), which
      were isolated from 17 of 20 (85%) and 19 of 20 (95%) tested prime lamb and mutton
      sheep properties, respectively. STEC isolates containing stx(1), stx(2), and ehxA
      were most commonly isolated (19 of 40 flocks; 47.5%), and this profile was
      observed for 10 different serotypes. Among 90 STEC isolates studied, the most
      common serotypes were O91:H(-) (22 isolates [24.4%]), O5:H(-) (16 isolates
      [17.8%]), O128:H2 (11 isolates [12.2%]), O123:H(-) (8 isolates [8.9%]), and
      O85:H49 (5 isolates [5.6%]). Two isolates (2.2%) were typed as O157:H(-). A total
      of 78 of 90 STEC isolates (86.7%) expressed Shiga toxin in Vero cell culture and
      75 of 84 ehxA-positive isolates (89.3%) expressed enterohemolysin on washed sheep
      blood agar. eaeA was observed in 11 of 90 (12.2%) ovine STEC isolates, including
      serotypes O5:H(-), O84:H(-), O85:H49, O123:H(-) O136:H40, and O157:H(-). Although
      only 2 of 90 isolates were typed as O157:H(-), the predominant serotypes
      recovered during this study have been recovered from human patients with clinical
      disease, albeit rarely.

PMID- 11326040
TI  - High prevalence of TT virus (TTV) and TTV-like minivirus in cervical swabs.
AB  - Genomes of TT virus (TTV) and TTV-like minivirus DNA were detected in 80% and 61%
      of cervical swabs from healthy women, respectively, regardless of concurrent
      human papillomavirus infection. These results show that the potential exists for
      sexual transmission of TTV and related viruses.

PMID- 11326041
TI  - Endocarditis caused by culture-negative organisms visible by Brown and Brenn
      staining: utility of PCR and DNA sequencing for diagnosis.
AB  - Two cases of culture-negative endocarditis with cocci seen in valve vegetations
      are presented. The organisms were identified by molecular analysis using broad
      range PCR primers complementary to the 16S rRNA gene, sequencing, and database
      search using BLAST software. The results and utility of this method are
      discussed.

PMID- 11326042
TI  - Capnocytophaga cynodegmi cellulitis, bacteremia, and pneumonitis in a diabetic
      man.
AB  - Capnocytophaga cynodegmi (formerly "DF-2 like organism"), a commensal organism of
      the canine oral cavity, is a capnophilic, gram-negative, facultative bacillus. C.
      cynodegmi has rarely been encountered in human diseases. We report the first
      known case of cellulitis, bacteremia, and pneumonitis caused by C. cynodegmi in a
      diabetic man from central India following a dog bite.

PMID- 11326043
TI  - Disseminated Mycobacterium lentiflavum infection in a human immunodeficiency
      virus-infected patient.
AB  - We report the first case of Mycobacterium lentiflavum disseminated infection in a
      human immunodeficiency virus-infected patient. Conventional identification
      procedures failed to identify the mycobacterial strain, but sequencing of the 16S
      rRNA gene led to the species identification. Furthermore, we describe here the
      analysis of the 16S-23S rRNA internal transcribed spacer sequence of M.
      lentiflavum.

PMID- 11326044
TI  - Mycobacterium triplex infection in a liver transplant patient.
AB  - Mycobacterium triplex was first named in 1996 as an acid-fast bacillus with
      features that most resemble Mycobacterium simiae and Mycobacterium avium
      intracellulare complex but which possesses a distinct mycolic acid pattern as
      well as a distinctive 16S rRNA hypervariable region. It has been isolated from
      lymph node, sputum, and cerebrospinal fluid specimens, but to date only rare
      clinical cases of this organism have been reported in the literature. The
      following is a case report of M. triplex that was isolated from the pericardial
      and peritoneal fluid of a 13-year-old female liver transplant patient.

PMID- 11326045
TI  - Roots: evolutionary origins and biogeochemical significance.
AB  - Roots, as organs distinguishable developmentally and anatomically from shoots
      (other than by occurrence of stomata and sporangia on above-ground organs),
      evolved in the sporophytes of at least two distinct lineages of early vascular
      plants during their initial major radiation on land in Early Devonian times (c.
      410-395 million years ago). This was some 15 million years after the appearance
      of tracheophytes and c. 50 million years after the earliest embryophytes of
      presumed bryophyte affinity. Both groups are known initially only from spores,
      but from comparative anatomy of extant bryophytes and later Lower Devonian
      fossils it is assumed that, during these times, below-ground structures (if any)
      other than true roots fulfilled the functions of anchorage and of water and
      nutrient acquisition, despite lacking an endodermis (as do the roots of extant
      Lycopodium spp.). By 375 million years ago root-like structures penetrated almost
      a metre into the substratum, greatly increasing the volume of mineral matter
      subject to weathering by the higher than atmospheric CO(2) levels generated by
      plant and microbial respiration in material with restricted diffusive contact
      with the atmosphere. Chemical weathering consumes CO(2) in converting silicates
      into bicarbonate and Si(OH)(4). The CO(2) consumed in weathering ultimately came
      from atmospheric CO(2) via photosynthesis and respiration; this use of CO(2)
      probably accounts for most of the postulated 10-fold decrease in atmospheric
      CO(2) from 400-350 million years ago, with significant effects on shoot
      evolution. Subsequent evolution of roots has yielded much-branched axes down to
      40 microm diameter, a lower limit set by long-distance transport constraints.
      Finer structures involved in the uptake of nutrients of low diffusivity in soil
      evolved at least 400 million years ago as arbuscular mycorrhizas or as
      evaginations of "roots" ("root hairs").

PMID- 11326046
TI  - The peri-cell-cycle in Arabidopsis.
AB  - The root systems of plants proliferate via de novo formed meristems originating
      from differentiated pericycle cells. The identity of putative signals responsible
      for triggering some of the pericycle cells to re-enter the cell cycle remains
      unknown. Here, the cell cycle regulation in the pericycle of seedling roots of
      Arabidopsis thaliana (L.) HEYNH: is studied shortly after germination using
      various strategies. Based on the detailed analysis of the promoter-beta
      glucuronidase activity of four key cell cycle regulatory genes, combined with
      cell length measurements, microdensitometry of DNA content, and experiments with
      a cell cycle-blocking agent, a model is proposed for cell cycle regulation in the
      pericycle at the onset of lateral root initiation. The results clearly show that
      before the first lateral root is initiated, the pericycle consists of dissimilar
      cell files in respect of their cell division history. Depending on the distance
      behind the root tip and on position in relation to the vascular tissue,
      particular pericycle cells remain in the G(2) phase of the cell cycle and are
      apparently more susceptible to lateral root initiation than others.

PMID- 11326047
TI  - Evolution and genetics of root hair stripes in the root epidermis.
AB  - Root hair pattern develops in a number of different ways in angiosperm. Cells in
      the epidermis of some species undergo asymmetric cell divisions to form a smaller
      daughter cell from which a hair grows, and a larger cell that forms a non-hair
      epidermal cell. In other species any cell in the epidermis can form a root hair.
      Hair cells are arranged in files along the Arabidopsis root, located in the gaps
      between underlying cortical cell files. Epidermal cells overlying a single
      cortical cell file develop as non-hair epidermal cells. Genetic analysis has
      identified a transcription factor cascade required for the formation of this
      pattern. WEREWOLF (WER) and GLABRA2 (GL2) are required for the formation of non
      hair epidermal cells while CAPRICE (CPC) is required for hair cell development.
      Recent analyses of the pattern of epidermal cells among the angiosperms indicate
      that this striped pattern of cell organization evolved from non-striped ancestors
      independently in a number of diverse evolutionary lineages. The genetic basis for
      the evolution of epidermal pattern in angiosperms may now be examined.

PMID- 11326048
TI  - Flavonoids induced in cells undergoing nodule organogenesis in white clover are
      regulators of auxin breakdown by peroxidase.
AB  - It was tested whether flavonoids that specifically accumulate in cells undergoing
      early nodule organogenesis could affect auxin turnover by a peroxidase to explain
      local changes in auxin distribution that occur during nodule formation in white
      clover (Trifolium repens cv. Haifa). A fluorometric assay was developed to
      determine the kinetics of indoleacetic acid (IAA) breakdown rates by a
      horseradish peroxidase in vitro. Three flavonoid compounds, which had previously
      been localized and identified, were purified from root tissue and their tissue
      concentrations estimated. A derivative of 7,4'-dihydroxyflavone (DHF), as well as
      free DHF, strongly inhibited auxin breakdown by peroxidase at concentrations
      estimated in the root tissue. Formononetin, an isoflavonoid accumulating in
      nodule primordia, accelerated auxin breakdown by peroxidase at concentrations
      estimated to be present in the roots. These results suggest that local changes in
      flavonoid accumulation could regulate local auxin levels during nodule
      organogenesis. The results are consistent with previous observations on the
      localization of auxin during nodule organogenesis. A model for the interaction of
      flavonoids with peroxidases is proposed to explain changes auxin during nodule
      development. A similar mechanism could be involved in lateral root and root gall
      formation.

PMID- 11326050
TI  - Nitrogen nutrition and the role of root-shoot nitrogen signalling particularly in
      symbiotic systems.
AB  - To obtain and concentrate reduced N from the environment, plants have evolved a
      diverse array of adaptations to utilize soil, biotic and atmospheric N. In
      symbiotic N(2)-fixing systems the potential for oversupply exists and regulation
      of activity to match demand is crucial. N status in plants is likely to be most
      strongly sensed in the shoot and signals translocated to the roots may involve
      phloem transported amino compounds or very low concentrations of specific signal
      molecules. The mechanism for sensing N status in plant cells is not understood at
      the molecular level although it may be expected to be similar in all plants.
      Mechanisms for the regulation of symbiotic N(2) fixation may be very different in
      the different symbiotic types. Rhizobia, Frankia and cyanobacteria are all
      symbiotic with different species of plants and the provision of O(2),
      carbohydrate or other nutrients may control symbiotic activity to varying extents
      in the different symbioses.

PMID- 11326049
TI  - N. plumbaginifolia zeaxanthin epoxidase transgenic lines have unaltered baseline
      ABA accumulations in roots and xylem sap, but contrasting sensitivities of ABA
      accumulation to water deficit.
AB  - A series of transgenic lines of Nicotiana plumbaginifolia with modified
      expression of zeaxanthin epoxidase gene (ZEP) provided contrasting ABA
      accumulation in roots and xylem sap. For mild water stress, concentration of ABA
      in the xylem sap ([ABA](xylem)) was clearly lower in plants underexpressing ZEP
      mRNA (complemented mutants and antisense transgenic lines) than in wild-type. In
      well-watered conditions, all lines presented similar [ABA](xylem) and similar ABA
      accumulation rates in detached roots. Plants could, therefore, be grown under
      normal light intensities and evaporative demand. Both ZEP mRNA abundance and ABA
      accumulation rate in roots increased with water deficit in all transgenic lines,
      except in complemented aba2-s1 mutants in which the ZEP gene was controlled by a
      constitutive promoter which does not respond to water deficit. These lines
      presented no change in root ABA content either with time or dehydration. The
      increase in ZEP mRNA abundance in roots with decreasing RWC was more pronounced
      in detached roots than in whole plants, suggesting a difference in mechanism. In
      all transgenic lines, a linear relationship was observed between predawn leaf
      water potential and [ABA](xylem), which could be reproduced in several
      experiments in the greenhouse and in the growth chamber. It is therefore possible
      to represent the effect of the transformation by a single parameter, thereby
      allowing the use of a quantitative approach to assist understanding of the
      behaviour of transgenic lines.

PMID- 11326051
TI  - Partitioning of nutrient transport processes in roots.
AB  - Roots have a range of cell types that each contribute to the acquisition of
      nutrients and their subsequent transfer to the xylem. The activities of these
      cells must be co-ordinated to ensure that delivery of nutrients to the shoot
      occurs at a rate that matches the demands of growth. The partitioning of
      transport processes between different cell types is thus essential for roots to
      function effectively. This partitioning is considered at the level of proteins,
      organelles and cells in relation to the accepted concepts of how nutrients are
      taken up by roots and delivered to the xylem. Using K+ as an example, the
      evidence underpinning current concepts is examined, gaps in understanding
      identified and the contribution of some new approaches assessed.

PMID- 11326052
TI  - Gene expression profiling of two related maize inbred lines with contrasting root
      lodging traits.
AB  - To assist breeding for increased resistance to root lodging in maize, an attempt
      was made to identify genes that are associated with root lodging by profiling
      mRNA expression from two inbreds with contrasting root-related traits. These two
      inbreds were derived from a common F(2) pool, selfed for several generations and
      showed 75% relatedness based on 106 genetic markers. Under field conditions, the
      two inbreds exhibited significant differences in root morphology and resistance
      to root lodging. Whole root tissue was collected at two developmental stages from
      inbred 100 and 101 grown in 2 years. RNA was isolated from both the V8 and V12
      stages, a few weeks prior to flowering. The RNA samples from the 1997 growing
      season were analysed by GeneCalling analysis, an open-ended mRNA profiling
      method. From over 13 500 cDNA fragments detected from each of the V8- and V12
      stage samples, 229 and 325 cDNA fragments, respectively, showed greater than 2
      fold differences between the two inbred lines. A total of 69 cDNA fragments that
      showed 2-fold or greater differences for both inbred lines were observed at both
      developmental stages. The gene identity and expression differences of several
      cDNA fragments were determined and confirmed by RNA gel blot analysis. Two genes
      out of five identified were homologous to a cytochrome P450 and the impedance
      induced protein, both showing high levels of expression in the roots of lodging
      resistant lines and low levels in the sensitive lines. These data provide the
      first clues of genes expressed in the roots during the formative stages of root
      development associated with root-lodging resistance.

PMID- 11326053
TI  - The arbuscular mycorrhizal symbiosis: a molecular review of the fungal dimension.
AB  - Mycorrhizal associations vary widely in structure and function, but the most
      common interaction is the arbuscular mycorrhizal (AM) symbiosis. This interaction
      is formed between the roots of over 80% of all terrestrial plant species and
      Zygomycete fungi from the Order Glomales. These fungi are termed AM fungi and are
      obligate symbionts which form endomycorrhizal symbioses. This symbiosis confers
      benefits directly to the host plant's growth and development through the
      acquisition of P and other mineral nutrients from the soil by the fungus. In
      addition, they may also enhance the plant's resistance to biotic and abiotic
      stresses. These beneficial effects of the AM symbiosis occur as a result of a
      complex molecular dialogue between the two symbiotic partners. Identifying the
      molecules involved in the dialogue is a prerequisite for a greater understanding
      of the symbiosis. Ongoing research attempts to understand the underlying dialogue
      and concomitant molecular changes occurring in the plant and the fungus during
      the establishment of a functioning AM symbiosis. This paper focuses on the
      molecular approaches being used to study AM fungal genes being expressed in the
      symbiotic and asymbiotic stages of its lifecycle. In addition, the importance of
      studying these fungi, in relation to understanding plant processes, is discussed
      briefly.

PMID- 11326054
TI  - Cluster roots: model experimental tools for key biological problems.
AB  - The cluster root is made up of a number of determinate rootlets tightly grouped
      along the parent root. Each rootlet grows for a limited time, and then the
      meristem stops dividing and differentiates. Following cessation of growth, an
      exudative burst occurs, wherein, over 2-3 d, large amounts of organic acids, as
      well as phosphatases and phenolics, are exuded from the rootlets. There is a
      concomitant acidification of the rhizosphere. It is suggested that the temporal
      and spatial predictability of developmental and functional events in these
      structures makes them valuable as experimental tools with which to investigate
      key issues in plant developmental biology, physiology, ecophysiology,
      evolutionary biology, and biotechnology.

PMID- 11326055
TI  - Microbial interactions and biocontrol in the rhizosphere.
AB  - The loss of organic material from the roots provides the energy for the
      development of active microbial populations in the rhizosphere around the root.
      Generally, saproptrophs or biotrophs such as mycorrhizal fungi grow in the
      rhizosphere in response to this carbon loss, but plant pathogens may also develop
      and infect a susceptible host, resulting in disease. This review examines the
      microbial interactions that can take place in the rhizosphere and that are
      involved in biological disease control. The interactions of bacteria used as
      biocontrol agents of bacterial and fungal plant pathogens, and fungi used as
      biocontrol agents of protozoan, bacterial and fungal plant pathogens are
      considered. Whenever possible, modes of action involved in each type of
      interaction are assessed with particular emphasis on antibiosis, competition,
      parasitism, and induced resistance. The significance of plant growth promotion
      and rhizosphere competence in biocontrol is also considered. Multiple microbial
      interactions involving bacteria and fungi in the rhizosphere are shown to provide
      enhanced biocontrol in many cases in comparison with biocontrol agents used
      singly. The extreme complexity of interactions that can occur in the rhizosphere
      is highlighted and some potential areas for future research in this area are
      discussed briefly.

PMID- 11326056
TI  - A free radical.
AB  - This chapter describes my research career, spanning the period from 1955 to 2000.
      My initial PhD work at the University of Southampton was concerned with the
      electronic structure and spectra of transition metal complexes and included
      studies of the electronic spin resonance (ESR) spectra of magnetically dilute
      single crystals. After a year at the University of Minnesota, I went to Cambridge
      University and for the next six years studied the ESR spectra of liquid phase
      organic free radicals. I commenced work on the microwave magnetic resonance (MMR)
      spectra of gaseous free radicals in 1965, and this work continued until 1975. I
      moved from Cambridge to Southampton in 1967. In 1975 I turned to the study of gas
      phase molecular ions, using ion beam methods. In the earlier years of this period
      I concentrated on simple fundamental species like H(+)2, HD(+), and H(+)3. In the
      later years until my retirement in 1999, I concentrated on the observation and
      analysis of microwave spectra involving energy levels lying very close to a
      dissociation asymptote. DEDICATION This chapter is dedicated to the memory of
      Harry E. Radford, who died while it was being written. Harry was a quiet and shy
      man, who often worked alone and never indulged in self-promotion. So far as I
      know, he was never awarded any medals or prizes, nor elected to any academies or
      learned societies. Nevertheless he was an experimentalist of the highest
      originality and quality, a theorist of true intellectual depth, and a remarkable
      pioneer in many of the techniques of studying free radicals that are now
      commonplace.

PMID- 11326057
TI  - State-to-state chemical reaction dynamics in polyatomic systems: case studies.
AB  - This review illustrates the experimental study of chemical reaction dynamics
      using methods that select the quantum states and energy of the reactants and
      determine the quantum states and energy of the products. The focus is reaction
      dynamics in systems in which at least one of the reactants or products is a
      polyatomic molecule. The approach taken is to select four prototype reaction
      systems as case studies to demonstrate the detail of information and insight that
      can come from such experiments. Thus, the review is selective and neither claims
      nor attempts to be comprehensive. Reference to and discussion of theoretical
      reaction dynamics are included where computational results directly connect with
      the experiments.

PMID- 11326058
TI  - Recent progress in infrared absorption techniques for elementary gas-phase
      reaction kinetics.
AB  - Sensitive and precise measurements of rate coefficients, branching fractions, and
      energy disposal from gas-phase radical reactions provide information about the
      mechanism of elementary reactions as well as furnish modelers of complicated
      chemical systems with rate data. This chapter describes the use of time-resolved
      infrared laser absorption as a tool for investigating gas-phase radical
      reactions, emphasizing the exploitation of the particular advantages of the
      technique. The reaction of Cl atoms with HD illustrates the complementarity of
      thermal kinetic measurements with molecular beam data. Measurements of second
      order reactions, such as the self-reactions of SiH3 and C3H3 radicals, and
      determinations of product branching fractions in reactions such as CN + O2 rely
      on the wide applicability of infrared absorption and on the straightforward
      relationship of absorption to absolute concentration. Finally, investigations of
      product vibrational distributions, as in the CN + H2 reaction, provide additional
      insight into the details of reaction mechanisms.

PMID- 11326059
TI  - Surface biology of DNA by atomic force microscopy.
AB  - The atomic force microscope operates on surfaces. Since surfaces occupy much of
      the space in living organisms, surface biology is a valid and valuable form of
      biology that has been difficult to investigate in the past owing to a lack of
      good technology. Atomic force microscopy (AFM) of DNA has been used to
      investigate DNA condensation for gene therapy, DNA mapping and sizing, and a few
      applications to cancer research and to nanotechnology. Some of the most exciting
      new applications for atomic force microscopy of DNA involve pulling on single DNA
      molecules to obtain measurements of single-molecule mechanics and thermodynamics.

PMID- 11326060
TI  - On the characteristics of migration of oligomeric DNA in polyacrylamide gels and
      in free solution.
AB  - We review a model for the free-solution electrophoretic mobility of oligomeric
      double-stranded (ds) DNA. We have found that the free-solution mobility of ds DNA
      increases as the molecular weight of the fragment increases, up to a few hundred
      base pairs. This insight is combined with recent advances in the nature of
      counterion condensation theory of very short DNA fragments to describe
      quantitatively the electrophoretic mobility of oligomeric single-stranded DNA in
      polyacrylamide gels. The model predicts, in agreement with recent experiments,
      that significant anomalous migration exists with short DNA sequences, the onset
      of which is dependent on the size of polyacrylamide gel pores. For terminal
      phosphate-labeled DNA fragments, the free-solution mobility is no longer
      proportional to the ratio of the total effective charge and the friction
      coefficient. These changes in properties affect the characteristics of migration
      of end-labeled DNA fragments in polyacrylamide gels.

PMID- 11326061
TI  - Mechanisms and kinetics of self-assembled monolayer formation.
AB  - Recent applications of various in situ techniques have dramatically improved our
      understanding of the self-organization process of adsorbed molecular monolayers
      on solid surfaces. The process involves several steps, starting with bulk
      solution transport and surface adsorption and continuing with the two-dimensional
      organization on the substrate of interest. This later process can involve passage
      through one or more intermediate surface phases and can often be described using
      two-dimensional nucleation and growth models. A rich picture has emerged that
      combines elements of surfactant adsorption at interfaces and epitaxial growth
      with the additional complication of long-chain molecules with many degrees of
      freedom.

PMID- 11326062
TI  - Crossed-beam studies of neutral reactions: state-specific differential cross
      sections.
AB  - Crossed-molecular-beam and laser techniques have enabled experimentalists to
      measure the state-resolved differential cross sections of elementary chemical
      reactions. This article reviews recent progress in this area. Particular emphasis
      is placed on some intriguing physical phenomena associated with a few benchmark
      reactions and how these measurements help in answering fundamental questions
      about reaction dynamics. We examine specifically the geometric phase effects in
      the reaction H + D2, the dynamical resonance phenomenon in F + HD, the unusually
      large spin-orbit reactivity in Cl((2)P) + H2, the insertion reaction O((1)D) +
      H2, and the mode-specific reactivity in Cl + CH4(nu). The give-and-take between
      experiment and theory in unraveling the physical picture of the dynamics is
      illustrated throughout this review.

PMID- 11326063
TI  - Coincidence spectroscopy.
AB  - The application of coincidence techniques to the study of the reaction dynamics
      of isolated molecules is reviewed. Coincidence spectroscopy is a powerful
      approach for carrying out a number of measurements. At its most basic level,
      coincidence techniques can identify the source of a specific signal, as in the
      well-known photoelectron-photoion coincidence approach used for several years. By
      carrying out coincidence experiments in an increasingly differential manner,
      correlated energy and angular distributions of reaction products may be recorded.
      Completely energy- and angle-resolved measurements of photoelectrons and ionic or
      neutral products can reveal molecular-frame photoelectron and photofragment
      angular distributions and aid in the characterization of dissociative states of
      molecules and ions. Recent work in this area is reviewed, including examples from
      studies of dissociative photodetachment, dissociative photoionization, time
      resolved studies of dissociative photoionization, and three-body dissociation
      processes.

PMID- 11326064
TI  - Spectroscopy and hot electron relaxation dynamics in semiconductor quantum wells
      and quantum dots.
AB  - Photoexcitation of a semiconductor with photons above the semiconductor band gap
      creates electrons and holes that are out of equilibrium. The rates at which the
      photogenerated charge carriers return to equilibrium via thermalization through
      carrier scattering, cooling by phonon emission, and radiative and nonradiative
      recombination are important issues. The relaxation processes can be greatly
      affected by quantization effects that arise when the carriers are confined to
      regions of space that are small compared with their deBroglie wavelength or the
      Bohr radius of bulk excitons. The effects of size quantization in semiconductor
      quantum wells (carrier confinement in one dimension) and quantum dots (carrier
      confinement in three dimensions) on the respective carrier relaxation processes
      are reviewed, with emphasis on electron cooling dynamics. The implications of
      these effects for applications involving radiant energy conversion are also
      discussed.

PMID- 11326066
TI  - Time-resolved photoelectron spectroscopy of molecules and clusters.
AB  - Time-resolved photoelectron spectroscopy (TRPES) has become a powerful new tool
      in studying the dynamics of molecules and clusters. It has been applied to
      processes ranging from energy flow in electronically excited states of molecules
      to electron solvation dynamics in clusters. This review covers experimental and
      theoretical aspects of TRPES, focusing on studies of neutral and negatively
      charged species.

PMID- 11326065
TI  - Ratiometric single-molecule studies of freely diffusing biomolecules.
AB  - We outline recent developments in biological single-molecule fluorescence
      detection with particular emphasis on observations by ratiometric fluorescence
      resonance energy transfer (FRET) of biomolecules freely diffusing in solution.
      Single-molecule-diffusion methodologies were developed to minimize perturbations
      introduced by interactions between molecules and surfaces. Confocal microscopy is
      used in combination with sensitive detectors to observe bursts of photons from
      fluorescently labeled biomolecules as they diffuse through the focal volume.
      These bursts are analyzed to extract ratiometric observables such as FRET
      efficiency and polarization anisotropy. We describe the development of single
      molecule FRET methodology and its application to the observation of the Forster
      distance dependence and the study of protein folding and polymer physics
      problems. Finally, we discuss future advances in data acquisition and analysis
      techniques that can provide a more complete picture of the accessible molecular
      information.

PMID- 11326067
TI  - Pulsed EPR spectroscopy: biological applications.
AB  - Pulsed electron paramagnetic resonance (EPR) methods such as ESEEM, PELDOR,
      relaxation time measurements, transient EPR, high-field/high-frequency EPR, and
      pulsed ENDOR, have been used successfully to investigate the local structure and
      dynamics of paramagnetic centers in biological samples. These methods allow
      different contributions to the EPR spectra to be distinguished and can help
      unravel complicated EPR spectra consisting of overlapping resonance lines, as are
      often found in disordered protein samples. The basic principles, specific
      potentials, technical requirements, and limitations of these advanced EPR
      techniques will be reviewed together with recent applications to metal centers,
      organic radicals, and spin labels in proteins.

PMID- 11326068
TI  - Fast protein dynamics probed with infrared vibrational echo experiments.
AB  - IR vibrational echo experiments are used to study dynamics in myoglobin (Mb) by
      investigating the dephasing of the CO-stretching mode of CO bound at the active
      site of the protein (Mb-CO). The temperature dependence and the viscosity
      dependence of Mb-CO pure dephasing have been measured in several solvents. In low
      temperature, glassy solvents, the pure dephasing has a power law temperature
      dependence, T(1.3), that reflects glasslike protein dynamics. In liquids, the
      temperature dependence is much steeper and arises from a combination of pure
      temperature dependence and the influence of decreasing solvent viscosity with
      increasing temperature. As the solvent viscosity decreases, the ability of the
      protein's surface to undergo topological fluctuations increases, which in turn
      increases the internal protein-structural fluctuations. The protein-structural
      motions are coupled to the CO bound at the active site by electric field
      fluctuations that accompany movements of polar residues. The dynamic electric
      field-coupling mechanism is tested by observing differences in the temperature
      dependence of the pure dephasing of Mb-CO mutations.

PMID- 11326069
TI  - Structure and bonding of molecules at aqueous surfaces.
AB  - Significant advances toward understanding the structure of aqueous surfaces on a
      molecular level have been made in recent years. This review focuses on the recent
      contributions of surface vibrational sum frequency spectroscopy (VSFS) to this
      field of study. An overview of recent VSFS studies of the molecular structure and
      orientation of molecules at the vapor-water interface and the interface between
      water and an immiscible organic liquid is presented, with particular emphasis on
      studies that compare the molecular properties and adsorbate behavior at these two
      different but related interfaces. This discussion is preceded by a general
      introduction to VSFS studies at aqueous surfaces and a description of the
      fundamental principles underlying the technique.

PMID- 11326070
TI  - Light-emitting electrochemical processes.
AB  - Electrochemical processes leading to light emission are reviewed, with emphasis
      on aspects of this subject relevant to the understanding and optimization of
      electrogenerated luminescence (EL) in organic thin-film materials. The basic
      energetic requirements of light emission from electrochemically initiated
      solution redox reactions [electrogenerated chemiluminescence (ECL)] are reviewed
      first. This review is followed by a discussion of light-emitting electrochemical
      processes that have been observed in hybrids of ionically conducting polymers and
      electronically conducting polymers. Finally, the features of EL in insulating
      polymers and molecular thin films are reviewed, along with recent electrochemical
      and ECL studies of the small-molecule components of certain organic light
      emitting diodes. These studies provide a conceptual framework for understanding
      and optimizing these materials and the EL process.

PMID- 11326071
TI  - Reactions and thermochemistry of small transition metal cluster ions.
AB  - This review discusses the reactivities and thermodynamics of small-size-specific
      transition metal clusters and focuses on thermodynamic information, which has not
      been comprehensively discussed before. Because of this focus, guided-ion-beam
      mass spectrometry was used to acquire much of the data. The details of this
      technique and the associated data analysis methods are provided. Results on the
      stabilities of bare transition metal clusters are provided for neutral, cationic,
      and anionic species. Implications for the electronic and geometrical structures
      are discussed, as well as the extrapolation of these values to bulk phase
      behavior. Detailed results for reactions of transition metal clusters with D2 and
      the oxygen donors O2 and CO2 are reviewed. Available bond energies between size
      specific clusters and one D atom and one and two O atoms are compiled, and their
      implications are evaluated and favorably compared with bulk phase analogs.
      Several additional thermodynamic studies of various cluster systems are also
      discussed.

PMID- 11326072
TI  - Spin-1/2 and beyond: a perspective in solid state NMR spectroscopy.
AB  - Novel applications of solid state nuclear magnetic resonance (NMR) to the study
      of small molecules, synthetic polymers, biological systems, and inorganic
      materials continue at an accelerated rate. Instrumental to this uninterrupted
      expansion has been an improved understanding of the chemical physics underlying
      NMR. Such deeper understanding has led to novel forms of controlling the various
      components that make up the spin interactions, which have in turn redefined the
      analytical capabilities of solid state NMR measurements. This review presents a
      perspective on the basic phenomena and manipulations that have made this progress
      possible and describes the new opportunities and challenges that are being opened
      in the realms of spin-1/2 and quadrupole nuclei spectroscopies.

PMID- 11326074
TI  - Polymer adsorption-driven self-assembly of nanostructures.
AB  - Driven by prospective applications, there is much interest in developing
      materials that can perform specific functions in response to external conditions.
      One way to design such materials is to create systems which, in response to
      external inputs, can self-assemble to form structures that are functionally
      useful. This review focuses on the principles that can be employed to design
      macromolecules that when presented with an appropriate two-dimensional surface,
      will self-assemble to form nanostructures that may be functionally useful. We
      discuss three specific examples: (a) biomimetic recognition between polymers and
      patterned surfaces. (b) control and manipulation of nanomechanical motion
      generated by biopolymer adsorption and binding, and (c) creation of patterned
      nanostructuctures by exposing molten diblock copolymers to patterned surfaces.
      The discussion serves to illustrate how polymer sequence can be manipulated to
      affect self-assembly characteristics near adsorbing surfaces. The focus of this
      review is on theoretical and computational work aimed toward elucidating the
      principles underlying the phenomena pertinent to the three topics noted above.
      However, synergistic experiments are also described in the appropriate context.

PMID- 11326073
TI  - From folding theories to folding proteins: a review and assessment of simulation
      studies of protein folding and unfolding.
AB  - Beginning with simplified lattice and continuum "minimalist" models and
      progressing to detailed atomic models, simulation studies have augmented and
      directed development of the modern landscape perspective of protein folding. In
      this review we discuss aspects of detailed atomic simulation methods applied to
      studies of protein folding free energy surfaces, using biased-sampling free
      energy methods and temperature-induced protein unfolding. We review studies from
      each on systems of particular experimental interest and assess the strengths and
      weaknesses of each approach in the context of "exact" results for both free
      energies and kinetics of a minimalist model for a beta-barrel protein. We
      illustrate in detail how each approach is implemented and discuss analysis
      methods that have been developed as components of these studies. We describe key
      insights into the relationship between protein topology and the folding mechanism
      emerging from folding free energy surface calculations. We further describe the
      determination of detailed "pathways" and models of folding transition states that
      have resulted from unfolding studies. Our assessment of the two methods suggests
      that both can provide, often complementary, details of folding mechanism and
      thermodynamics, but this success relies on (a) adequate sampling of diverse
      conformational regions for the biased-sampling free energy approach and (b) many
      trajectories at multiple temperatures for unfolding studies. Furthermore, we find
      that temperature-induced unfolding provides representatives of folding
      trajectories only when the topology and sequence (energy) provide a relatively
      funneled landscape and "off-pathway" intermediates do not exist.

PMID- 11326075
TI  - Biomolecular solid state NMR: advances in structural methodology and applications
      to peptide and protein fibrils.
AB  - Solid state nuclear magnetic resonance (NMR) methods can provide atomic-level
      structural constraints on peptides and proteins in forms that are not amenable to
      characterization by other high-resolution structural techniques, owing to
      insolubility, high molecular weight, noncrystallinity, or other characteristics.
      Important examples include peptide and protein fibrils and membrane-bound
      peptides and proteins. Recent advances in solid state NMR methodology aimed at
      structural problems in biological systems are reviewed. The power of these
      methods is illustrated by experimental results on amyloid fibrils and other
      protein fibrils.

PMID- 11326076
TI  - Photofragment translational spectroscopy of weakly bound complexes: probing the
      interfragment correlated final state distributions.
AB  - The vibrational predissociation dynamics of weakly bound complexes is well known
      to be highly nonstatistical. In particular, the associated photofragment final
      state distributions are often far from statistical, consequently reflecting the
      nature of the dissociation process. For binary complexes consisting of two
      molecules, a complete description of the final state of the system must include
      the associated interfragment correlations, specifically between their internal
      states. Information of this type is imprinted in the translational energies of
      the fragments, which can be measured using a number of recently developed
      translational spectroscopy methods. These data can provide detailed insights into
      the nature of the bond rupture process, as well as accurate values for the
      dissociation energy of the complexes. The focus of the present review is on
      experiments that provide correlated final state distributions for weakly bound
      binary complexes. Where possible, comparisons with theoretical calculations are
      made.

PMID- 11326077
TI  - Coherent nonlinear spectroscopy: from femtosecond dynamics to control.
AB  - This review focuses on the study of the dynamics of isolated molecules and their
      control using coherent nonlinear spectroscopic methods. Emphasis is placed on
      topics such as bound-to-free excitation and the study of concerted elimination
      reactions, free-to-bound excitation and the study of bimolecular reactions, and
      bound-to-bound excitation and the study of intramolecular rovibrational dynamics
      and coherence relaxation. For each case the detailed time-resolved information
      reveals possible strategies to control the outcome. Experimental results are
      shown for each of the reactions discussed. The methods discussed include pump
      probe and four-wave mixing processes such as transient grating and photon echo
      spectroscopy. Off-resonance transient-grating experiments are shown to be ideal
      for the study of ground state dynamics, molecular structure, and the molecular
      response to strong field excitation.

PMID- 11326078
TI  - Electron transmission through molecules and molecular interfaces.
AB  - Electron transmission through molecules and molecular interfaces has been a
      subject of intensive research due to recent interest in electron-transfer
      phenomena underlying the operation of the scanning-tunneling microscope on one
      hand, and in the transmission properties of molecular bridges between conducting
      leads on the other. In these processes, the traditional molecular view of
      electron transfer between donor and acceptor species gives rise to a novel view
      of the molecule as a current-carrying conductor, and observables such as electron
      transfer rates and yields are replaced by the conductivities, or more generally
      by current-voltage relationships, in molecular junctions. Such investigations of
      electrical junctions, in which single molecules or small molecular assemblies
      operate as conductors, constitute a major part of the active field of molecular
      electronics. In this article I review the current knowledge and understanding of
      this field, with particular emphasis on theoretical issues. Different approaches
      to computing the conduction properties of molecules and molecular assemblies are
      reviewed, and the relationships between them are discussed. Following a detailed
      discussion of static-junctions models, a review of our current understanding of
      the role played by inelastic processes, dephasing and thermal-relaxation effects
      is provided. The most important molecular environment for electron transfer and
      transmission is water, and our current theoretical understanding of electron
      transmission through water layers is reviewed. Finally, a brief discussion of
      overbarrier transmission, exemplified by photoemission through adsorbed molecular
      layers or low-energy electron transmission through such layers, is provided.
      Similarities and differences between the different systems studied are discussed.

PMID- 11326079
TI  - Early events in RNA folding.
AB  - We describe a conceptual framework for understanding the way large RNA molecules
      fold based on the notion that their free-energy landscape is rugged. A key
      prediction of our theory is that RNA folding can be described by the kinetic
      partitioning mechanism (KPM). According to KPM a small fraction of molecules
      folds rapidly to the native state whereas the remaining fraction is kinetically
      trapped in a low free-energy non-native state. This model provides a unified
      description of the way RNA and proteins fold. Single-molecule experiments on
      Tetrahymena ribozyme, which directly validate our theory, are analyzed using KPM.
      We also describe the earliest events that occur on microsecond time scales in RNA
      folding. These must involve collapse of RNA molecules that are mediated by
      counterion-condensation. Estimates of time scales for the initial events in RNA
      folding are provided for the Tetrahymena ribozyme.

PMID- 11326080
TI  - Laser-induced population transfer by adiabatic passage techniques.
AB  - We review some basic techniques for laser-induced adiabatic population transfer
      between discrete quantum states in atoms and molecules.

PMID- 11326081
TI  - The dynamics of "stretched molecules": experimental studies of highly
      vibrationally excited molecules with stimulated emission pumping.
AB  - We review stimulated emission pumping as used to study molecular dynamics. The
      review presents unimolecular as well as scattering studies. Topics include
      intramolecular vibrational redistribution, unimolecular isomerization and
      dissociation, van der Waals clusters, rotational energy transfer, vibrational
      energy transfer, gas-surface interactions, atmospheric effects resulting from
      nonequilibrium vibrational excitation, and vibrational promotion of electron
      transfer.

PMID- 11326083
TI  - Evidence for dust grain growth in young circumstellar disks.
AB  - Hundreds of circumstellar disks in the Orion nebula are being rapidly destroyed
      by the intense ultraviolet radiation produced by nearby bright stars. These
      young, million-year-old disks may not survive long enough to form planetary
      systems. Nevertheless, the first stage of planet formation-the growth of dust
      grains into larger particles-may have begun in these systems. Observational
      evidence for these large particles in Orion's disks is presented. A model of
      grain evolution in externally irradiated protoplanetary disks is developed and
      predicts rapid particle size evolution and sharp outer disk boundaries. We
      discuss implications for the formation rates of planetary systems.

PMID- 11326082
TI  - Differentiation of embryonic stem cells to insulin-secreting structures similar
      to pancreatic islets.
AB  - Although the source of embryonic stem (ES) cells presents ethical concerns, their
      use may lead to many clinical benefits if differentiated cell types can be
      derived from them and used to assemble functional organs. In pancreas, insulin is
      produced and secreted by specialized structures, islets of Langerhans. Diabetes,
      which affects 16 million people in the United States, results from abnormal
      function of pancreatic islets. We have generated cells expressing insulin and
      other pancreatic endocrine hormones from mouse ES cells. The cells self-assemble
      to form three-dimensional clusters similar in topology to normal pancreatic
      islets where pancreatic cell types are in close association with neurons. Glucose
      triggers insulin release from these cell clusters by mechanisms similar to those
      employed in vivo. When injected into diabetic mice, the insulin-producing cells
      undergo rapid vascularization and maintain a clustered, islet-like organization.

PMID- 11326084
TI  - Fermi surface nesting and nanoscale fluctuating charge/orbital ordering in
      colossal magnetoresistive oxides.
AB  - We used high-resolution angle-resolved photoemission spectroscopy to reveal the
      Fermi surface and key transport parameters of the metallic state of the layered
      colossal magnetoresistive oxide La1.2Sr1.8Mn2O7. With these parameters, the
      calculated in-plane conductivity is nearly one order of magnitude larger than the
      measured direct current conductivity. This discrepancy can be accounted for by
      including the pseudogap, which removes at least 90% of the spectral weight at the
      Fermi energy. Key to the pseudogap and to many other properties are the parallel
      straight Fermi surface sections, which are highly susceptible to nesting
      instabilities. These nesting instabilities produce nanoscale fluctuating
      charge/orbital modulations, which cooperate with Jahn-Teller distortions and
      compete with the electron itinerancy favored by double exchange.

PMID- 11326086
TI  - Physics. Quasi-particles survive--for now.

PMID- 11326085
TI  - Autosomal recessive hypercholesterolemia caused by mutations in a putative LDL
      receptor adaptor protein.
AB  - Atherogenic low density lipoproteins are cleared from the circulation by hepatic
      low density lipoprotein receptors (LDLR). Two inherited forms of
      hypercholesterolemia result from loss of LDLR activity: autosomal dominant
      familial hypercholesterolemia (FH), caused by mutations in the LDLR gene, and
      autosomal recessive hypercholesterolemia (ARH), of unknown etiology. Here we map
      the ARH locus to an approximately 1-centimorgan interval on chromosome 1p35 and
      identify six mutations in a gene encoding a putative adaptor protein (ARH). ARH
      contains a phosphotyrosine binding (PTB) domain, which in other proteins binds
      NPXY motifs in the cytoplasmic tails of cell-surface receptors, including the
      LDLR. ARH appears to have a tissue-specific role in LDLR function, as it is
      required in liver but not in fibroblasts.

PMID- 11326087
TI  - Mechanisms underlying antigen-specific CD8+ T cell homeostasis.

PMID- 11326088
TI  - The evolution of climate over the last millennium.
AB  - Knowledge of past climate variability is crucial for understanding and modeling
      current and future climate trends. This article reviews present knowledge of
      changes in temperatures and two major circulation features-El Nino-Southern
      Oscillation (ENSO) and the North Atlantic Oscillation (NAO)-over much of the last
      1000 years, mainly on the basis of high-resolution paleoclimate records. Average
      temperatures during the last three decades were likely the warmest of the last
      millennium, about 0.2 degrees C warmer than during warm periods in the 11th and
      12th centuries. The 20th century experienced the strongest warming trend of the
      millennium (about 0.6 degrees C per century). Some recent changes in ENSO may
      have been unique since 1800, whereas the recent trend to more positive NAO values
      may have occurred several times since 1500. Uncertainties will only be reduced
      through more extensive spatial sampling of diverse proxy climatic records.

PMID- 11326089
TI  - Range shifts and adaptive responses to Quaternary climate change.
AB  - Tree taxa shifted latitude or elevation range in response to changes in
      Quaternary climate. Because many modern trees display adaptive differentiation in
      relation to latitude or elevation, it is likely that ancient trees were also so
      differentiated, with environmental sensitivities of populations throughout the
      range evolving in conjunction with migrations. Rapid climate changes challenge
      this process by imposing stronger selection and by distancing populations from
      environments to which they are adapted. The unprecedented rates of climate
      changes anticipated to occur in the future, coupled with land use changes that
      impede gene flow, can be expected to disrupt the interplay of adaptation and
      migration, likely affecting productivity and threatening the persistence of many
      species.

PMID- 11326090
TI  - Sea level change through the last glacial cycle.
AB  - Sea level change during the Quaternary is primarily a consequence of the cyclic
      growth and decay of ice sheets, resulting in a complex spatial and temporal
      pattern. Observations of this variability provide constraints on the timing,
      rates, and magnitudes of the changes in ice mass during a glacial cycle, as well
      as more limited information on the distribution of ice between the major ice
      sheets at any time. Observations of glacially induced sea level changes also
      provide information on the response of the mantle to surface loading on time
      scales of 10(3) to 10(5) years. Regional analyses indicate that the earth
      response function is depth dependent as well as spatially variable. Comprehensive
      models of sea level change enable the migration of coastlines to be predicted
      during glacial cycles, including the anthropologically important period from
      about 60,000 to 20,000 years ago.

PMID- 11326091
TI  - Trends, rhythms, and aberrations in global climate 65 Ma to present.
AB  - Since 65 million years ago (Ma), Earth's climate has undergone a significant and
      complex evolution, the finer details of which are now coming to light through
      investigations of deep-sea sediment cores. This evolution includes gradual trends
      of warming and cooling driven by tectonic processes on time scales of 10(5) to
      10(7) years, rhythmic or periodic cycles driven by orbital processes with 10(4)-
      to 10(6)-year cyclicity, and rare rapid aberrant shifts and extreme climate
      transients with durations of 10(3) to 10(5) years. Here, recent progress in
      defining the evolution of global climate over the Cenozoic Era is reviewed. We
      focus primarily on the periodic and anomalous components of variability over the
      early portion of this era, as constrained by the latest generation of deep-sea
      isotope records. We also consider how this improved perspective has led to the
      recognition of previously unforeseen mechanisms for altering climate.

PMID- 11326092
TI  - Dominant-negative mutants of a toxin subunit: an approach to therapy of anthrax.
AB  - The protective antigen moiety of anthrax toxin translocates the toxin's enzymic
      moieties to the cytosol of mammalian cells by a mechanism that depends on its
      ability to heptamerize and insert into membranes. We identified dominant-negative
      mutants of protective antigen that co-assemble with the wild-type protein and
      block its ability to translocate the enzymic moieties across membranes. These
      mutants strongly inhibited toxin action in cell culture and in an animal
      intoxication model, suggesting that they could be useful in therapy of anthrax.

PMID- 11326093
TI  - Energy gaps in "metallic" single-walled carbon nanotubes.
AB  - Metallic single-walled carbon nanotubes have been proposed to be good one
      dimensional conductors. However, the finite curvature of the graphene sheet that
      forms the nanotubes and the broken symmetry due to the local environment may
      modify their electronic properties. We used low-temperature atomically resolved
      scanning tunneling microscopy to investigate zigzag and armchair nanotubes, both
      thought to be metallic. "Metallic" zigzag nanotubes were found to have energy
      gaps with magnitudes that depend inversely on the square of the tube radius,
      whereas isolated armchair tubes do not have energy gaps. Additionally, armchair
      nanotubes packed in bundles have pseudogaps, which exhibit an inverse dependence
      on tube radius. These observed energy gaps suggest that most "metallic" single
      walled nanotubes are not true metals, and they have implications for our
      understanding of the electronic properties and potential applications of carbon
      nanotubes.

PMID- 11326094
TI  - Engineering carbon nanotubes and nanotube circuits using electrical breakdown.
AB  - Carbon nanotubes display either metallic or semiconducting properties. Both
      large, multiwalled nanotubes (MWNTs), with many concentric carbon shells, and
      bundles or "ropes" of aligned single-walled nanotubes (SWNTs), are complex
      composite conductors that incorporate many weakly coupled nanotubes that each
      have a different electronic structure. Here we demonstrate a simple and reliable
      method for selectively removing single carbon shells from MWNTs and SWNT ropes to
      tailor the properties of these composite nanotubes. We can remove shells of MWNTs
      stepwise and individually characterize the different shells. By choosing among
      the shells, we can convert a MWNT into either a metallic or a semiconducting
      conductor, as well as directly address the issue of multiple-shell transport.
      With SWNT ropes, similar selectivity allows us to generate entire arrays of
      nanoscale field-effect transistors based solely on the fraction of semiconducting
      SWNTs.

PMID- 11326095
TI  - A complex pattern of mantle flow in the Lau backarc.
AB  - Shear-wave splitting analysis of local events recorded on land and on the ocean
      floor in the Tonga arc and Lau backarc indicate a complex pattern of azimuthal
      anisotropy that cannot be explained by mantle flow coupled to the downgoing
      plate. These observations suggest that the direction of mantle flow rotates from
      convergence-parallel in the Fiji plateau to north-south beneath the Lau basin and
      arc-parallel beneath the Tonga arc. These results correlate with helium isotopes
      that map mantle flow of the Samoan plume into the Lau basin through an opening
      tear in the Pacific plate.

PMID- 11326096
TI  - Detection of widespread fluids in the Tibetan crust by magnetotelluric studies.
AB  - Magnetotelluric exploration has shown that the middle and lower crust is
      anomalously conductive across most of the north-to-south width of the Tibetan
      plateau. The integrated conductivity (conductance) of the Tibetan crust ranges
      from 3000 to greater than 20,000 siemens. In contrast, stable continental regions
      typically exhibit conductances from 20 to 1000 siemens, averaging 100 siemens.
      Such pervasively high conductance suggests that partial melt and/or aqueous
      fluids are widespread within the Tibetan crust. In southern Tibet, the high
      conductivity layer is at a depth of 15 to 20 kilometers and is probably due to
      partial melt and aqueous fluids in the crust. In northern Tibet, the conductive
      layer is at 30 to 40 kilometers and is due to partial melting. Zones of fluid may
      represent weaker areas that could accommodate deformation and lower crustal flow.

PMID- 11326097
TI  - Observations of ozone formation in power plant plumes and implications for ozone
      control strategies.
AB  - Data taken in aircraft transects of emissions plumes from rural U.S. coal-fired
      power plants were used to confirm and quantify the nonlinear dependence of
      tropospheric ozone formation on plume NO(x) (NO plus NO(2)) concentration, which
      is determined by plant NO(x) emission rate and atmospheric dispersion. The
      ambient availability of reactive volatile organic compounds, principally biogenic
      isoprene, was also found to modulate ozone production rate and yield in these
      rural plumes. Differences of a factor of 2 or greater in plume ozone formation
      rates and yields as a function of NO(x) and volatile organic compound
      concentrations were consistently observed. These large differences suggest that
      consideration of power plant NO(x) emission rates and geographic locations in
      current and future U.S. ozone control strategies could substantially enhance the
      efficacy of NO(x) reductions from these sources.

PMID- 11326098
TI  - Dating Caral, a preceramic site in the Supe Valley on the central coast of Peru.
AB  - Radiocarbon dates from the site of Caral in the Supe Valley of Peru indicate that
      monumental corporate architecture, urban settlement, and irrigation agriculture
      began in the Americas by 4090 years before the present (2627 calibrated years
      B.C.) to 3640 years before the present (1977 calibrated years B.C.). Caral is
      located 23 kilometers inland from the Pacific coast and contains a central zone
      of monumental, residential, and nonresidential architecture covering an area of
      65 hectares. Caral is one of 18 large preceramic sites in the Supe Valley.

PMID- 11326099
TI  - Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and
      death.
AB  - Multiple death signals influence mitochondria during apoptosis, yet the critical
      initiating event for mitochondrial dysfunction in vivo has been unclear. tBID,
      the caspase-activated form of a "BH3-domain-only" BCL-2 family member, triggers
      the homooligomerization of "multidomain" conserved proapoptotic family members
      BAK or BAX, resulting in the release of cytochrome c from mitochondria. We find
      that cells lacking both Bax and Bak, but not cells lacking only one of these
      components, are completely resistant to tBID-induced cytochrome c release and
      apoptosis. Moreover, doubly deficient cells are resistant to multiple apoptotic
      stimuli that act through disruption of mitochondrial function: staurosporine,
      ultraviolet radiation, growth factor deprivation, etoposide, and the endoplasmic
      reticulum stress stimuli thapsigargin and tunicamycin. Thus, activation of a
      "multidomain" proapoptotic member, BAX or BAK, appears to be an essential gateway
      to mitochondrial dysfunction required for cell death in response to diverse
      stimuli.

PMID- 11326100
TI  - Allosteric control of RNA polymerase by a site that contacts nascent RNA
      hairpins.
AB  - DNA, RNA, and regulatory molecules control gene expression through interactions
      with RNA polymerase (RNAP). We show that a short alpha helix at the tip of the
      flaplike domain that covers the RNA exit channel of RNAP contacts a nascent RNA
      stem-loop structure (hairpin) that inhibits transcription, and that this flap-tip
      helix is required for activity of the regulatory protein NusA. Protein-RNA cross
      linking, molecular modeling, and effects of alterations in RNAP and RNA all
      suggest that a tripartite interaction of RNAP, NusA, and the hairpin inhibits
      nucleotide addition in the active site, which is located 65 angstroms away. These
      findings favor an allosteric model for regulation of transcript elongation.

PMID- 11326101
TI  - Reversible unfolding of single RNA molecules by mechanical force.
AB  - Here we use mechanical force to induce the unfolding and refolding of single RNA
      molecules: a simple RNA hairpin, a molecule containing a three-helix junction,
      and the P5abc domain of the Tetrahymena thermophila ribozyme. All three molecules
      (P5abc only in the absence of Mg2+) can be mechanically unfolded at equilibrium,
      and when kept at constant force within a critical force range, are bi-stable and
      hop between folded and unfolded states. We determine the force-dependent
      equilibrium constants for folding/unfolding these single RNA molecules and the
      positions of their transition states along the reaction coordinate.

PMID- 11326102
TI  - Switching repulsion to attraction: changing responses to slit during transition
      in mesoderm migration.
AB  - Slit is secreted by cells at the midline of the central nervous system, where it
      binds to Roundabout (Robo) receptors and functions as a potent repellent. We
      found that migrating mesodermal cells in vivo respond to Slit as both an
      attractant and a repellent and that Robo receptors are required for both
      functions. Mesoderm cells expressing Robo receptors initially migrate away from
      Slit at the midline. A few hours after migration, these same cells change their
      behavior and require Robo to extend toward Slit-expressing muscle attachment
      sites. Thus, Slit functions as a chemoattractant to provide specificity for
      muscle patterning.

PMID- 11326103
TI  - Differentiation of embryonic stem cell lines generated from adult somatic cells
      by nuclear transfer.
AB  - Embryonic stem (ES) cells are fully pluripotent in that they can differentiate
      into all cell types, including gametes. We have derived 35 ES cell lines via
      nuclear transfer (ntES cell lines) from adult mouse somatic cells of inbred,
      hybrid, and mutant strains. ntES cells contributed to an extensive variety of
      cell types, including dopaminergic and serotonergic neurons in vitro and germ
      cells in vivo. Cloning by transfer of ntES cell nuclei could result in normal
      development of fertile adults. These studies demonstrate the full pluripotency of
      ntES cells.

PMID- 11326104
TI  - Molecular analyses of oral polio vaccine samples.
AB  - It has been suggested that the human immunodeficiency virus (HIV), and thus the
      acquired immunodeficiency syndrome (AIDS) it causes, was inadvertently introduced
      to humans by the use of an oral polio vaccine (OPV) during a vaccination campaign
      launched by the Wistar Institute, Philadelphia, PA, USA, in the Belgian Congo in
      1958 and 1959. The "OPV/AIDS hypothesis" suggests that the OPV used in this
      campaign was produced in chimpanzee kidney epithelial cell cultures rather than
      in monkey kidney cell cultures, as stated by H. Koprowski and co-workers, who
      produced the OPV. If chimpanzee cells were indeed used, this would lend support
      to the OPV/AIDS hypothesis, since chimpanzees harbor a simian immunodeficiency
      virus, widely accepted to be the origin of HIV-1. We analyzed several early OPV
      pools and found no evidence for the presence of chimpanzee DNA; by contrast,
      monkey DNA is present.

PMID- 11326105
TI  - Virus maturation involving large subunit rotations and local refolding.
AB  - Large-scale conformational changes transform viral precursors into infectious
      virions. The structure of bacteriophage HK97 capsid, Head-II, was recently solved
      by crystallography, revealing a catenated cross-linked topology. We have
      visualized its precursor, Prohead-II, by cryoelectron microscopy and modeled the
      conformational change by appropriately adapting Head-II. Rigid-body rotations (
      approximately 40 degrees) cause switching to an entirely different set of
      interactions; in addition, two motifs undergo refolding. These changes stabilize
      the capsid by increasing the surface area buried at interfaces and bringing the
      cross-link-forming residues, initially approximately 40 angstroms apart, close
      together. The inner surface of Prohead-II is negatively charged, suggesting that
      the transition is triggered electrostatically by DNA packaging.

PMID- 11326106
TI  - Distinction between space groups having principal rotation and screw axes, which
      are combined with twofold rotation axes, using the coherent convergent-beam
      electron diffraction method.
AB  - 23 sets of space groups remain indistinguishable by the convergent-beam electron
      diffraction (CBED) method. Recently, Tsuda, Saitoh, Terauchi, Tanaka & Goodman
      [Acta Cryst. (2000), A56, 359-369] demonstrated that the coherent CBED method can
      distinguish two space-group pairs (I23, I2(1)3) and (I222, I2(1)2(1)2(1)) by
      observing the relative arrangements of 2-fold-rotation and 2(1)-screw axes. The
      other ten space-group sets, which are composed of principal rotation and screw
      axes and other 2-fold-rotation axes such as P321 and P3(1)21 (P3(2)21), are shown
      to be distinguishable using the coherent CBED method.

PMID- 11326107
TI  - Statistical dynamical direct methods. II. The three-phase structure invariant.
AB  - The triplet distribution used for kinematical diffraction is extended to the
      complex case appropriate for dynamical transmission electron diffraction. It is
      demonstrated that this gives good results if the distributions are handled
      statistically rather than relying upon single triplet relationships. As a
      consequence, conventional statistical direct methods will yield a reasonable
      approximation to the effective dynamical potential for thicknesses when
      kinematical theory is not appropriate. The recovered effective dynamical
      potential may be similar to the kinematical potential, but does not have to be
      and in general will not be.

PMID- 11326108
TI  - Improvement of SAS triple invariant estimates for macromolecular direct-methods
      phasing.
AB  - Single-wavelength anomalous dispersion (SAS) data can in principle be phased by
      direct methods since a priori estimates of the three-phase structure invariants
      can be computed from these data. The mean phase error of the most reliable triple
      estimates for a small protein, however, is typically no better than 60 degrees,
      and does not bode well for applications to larger structures. A procedure is
      described that can substantially lower the error in these estimates and introduce
      a larger number of useful triple invariants into the phasing process. The mean
      phase error of the most reliable triples for a 2.5 A resolution data set from a
      Pt derivative of a 115-residue protein was reduced from 55 to 25 degrees by this
      method. It was also possible to identify a significant number of the poorest
      triple estimates, those with mean phase errors approaching 90 degrees, such that
      they could be reliably down-weighted or excluded from the phasing process.

PMID- 11326109
TI  - Diffuse X-ray scattering and strain effects in disordered crystals.
AB  - It is shown in this paper that a feature that has been observed in the diffuse
      scattering patterns of a wide variety of different materials - a diffuse 'ring'
      or 'doughnut'-shaped region of scattering - can be understood in terms of a
      simple model that has been borrowed from the field of sol-gel science. In this,
      it is supposed that there is a balance between the local attractive forces that
      are trying to make a particular structure and a rather longer range repulsive
      force. In the present context, it is believed that this latter force has its
      origin in the strain that builds as the preferred local structure tries to fit
      into the average crystal lattice. Simple Monte Carlo (MC) computer simulations
      are described that demonstrate this principle for three example materials: cubic
      stabilized zirconia, the p-didecylbenzene/urea inclusion compound and the pure
      molecular compound 1,3-dibromo-2,5-diethyl-4,6-dimethylbenzene, C12H16Br2
      (BEMB2).

PMID- 11326110
TI  - Notes on the normalizer of a finite subgroup of GL(n,d,Z) in GL(n,d,Z).
AB  - A finite algorithm for calculating a finite set of generators for the normalizer
      of a finite subgroup G of GL(n,d,Z) in GL(n,d,Z) is presented. It is based on an
      algorithm for the normalizer of a finite subgroup G in GL(n,Z), which has been
      developed recently by Opgenorth. The normalizer of G in GL(n,d,Z) plays a role
      for superspace groups analogous to the role that the normalizer of G in GL(n,Z)
      plays for n-dimensional space groups. It is important for calculating superspace
      groups with the Zassenhaus algorithm and is needed for testing equivalence of
      superspace groups.

PMID- 11326111
TI  - Interatomic potential parameters for potassium tetrachlorozincate and their
      application to modelling its phase transformations.
AB  - An empirical fitting procedure is applied to derive interatomic potential
      parameters for a model phase transition system, namely potassium
      tetrachlorozincate (K(2)ZnCl(4)). The derived potential is found to reliably
      model the known crystallographic structure for the ferroelectric and paraelectric
      phases of this compound. Potential transferability is demonstrated by applying
      the parameters derived to the optimization of the known molecular structure for a
      similar inorganic system (rubidium tetrachlorozincate).

PMID- 11326112
TI  - Density-optimized radial exponents for X-ray charge-density refinement from ab
      initio crystal calculations.
AB  - Structure factors based on periodic density-functional (DFT) calculations on 25
      molecular crystals have been used to evaluate trends in refined values of the
      kappa and kappa' expansion-contraction parameters of the Hansen-Coppens multipole
      formalism. As found previously and expected physically, the spherical-valence
      shell kappa parameters are closely related to the net atomic charges, negative
      atoms being expanded and vice versa. kappa' parameters, which scale the radial
      dependence of the non-spherical deformation functions, are remarkably consistent
      for particular bonding environments. Systematic trends are observed for both
      carbon and oxygen, but the values obtained for nitrogen show a larger variation.
      Average values for oxygen and carbon in different bonding environments are
      tabulated and can be used whenever refinement of experimental data is affected by
      lack of uniqueness of the charge-density parameter set. Values for nitrogen must
      be more finely tuned to the specific bonding environment. The relation between
      atomic charge and kappa offers the possibility of introducing a constraint in the
      charge-density refinement of very large molecules, for which reduction of the
      size of the parameter set may be essential.

PMID- 11326113
TI  - Interference of parametric X-ray and coherent Bremsstrahlung radiation from
      nonrelativistic electrons: application to the phase analysis in crystallography.
AB  - The intensity of coherent X-radiation (CXR) from a relativistic electron beam
      interacting with the crystal [Feranchuk, Ulyanenkov, Harada & Spence (2000).
      Phys. Rev. E, 62, 4225-4234] is studied in view of its application to the phase
      determination problem. The analysis of CXR spectra is shown to permit an
      independent measurement of unit-cell structure factors, defined by both the
      electron-density distribution and the nucleus positions. In relation to these
      structure factors, two new types of Patterson function are introduced that can
      simplify the solution of crystal structure.

PMID- 11326114
TI  - Recovering experimental and theoretical electron densities in corundum using the
      multipolar model: IUCr Multipole Refinement Project.
AB  - This electron-density study on corundum (alpha-Al2O3) is part of the Multipole
      Refinement Project supported by the IUCr Commission on Charge, Spin and Momentum
      Densities. For this purpose, eight different data sets (two experimental and six
      theoretical) were chosen from which the electron density was derived by
      multipolar refinement (using the MOLLY program). The two experimental data sets
      were collected on a conventional CAD4 and at ESRF, ID11 with a CCD detector,
      respectively. The theoretical data sets consist of static, dynamic, static noisy
      and dynamic noisy moduli of structure factors calculated at the Hartree-Fock (HF)
      and density functional theory (DFT) levels. Comparisons of deformation and
      residual densities show that the multipolar analysis works satisfactorily but
      also indicate some drawbacks in the refinement. Some solutions and improvements
      during the refinements are proposed like contraction or expansion of the inner
      atomic shells or increasing the order of the spherical harmonic expansion.

PMID- 11326115
TI  - Symmetry of single-wall nanotubes.
AB  - Nanotubes have become attractive subjects in solid-state physics owing to their
      potential applications in nanotechnology. Their symmetry is one of the important
      tools in theoretical investigations. Here a review is presented of the symmetry
      groups of the single-wall nano- and microtubes considered in literature: BN, GaN,
      MS2, C, BC3, BC2N.

PMID- 11326116
TI  - The application of Hermann's group M in group-subgroup relations between space
      groups.
AB  - This paper is devoted to the study of the group-subgroup relations U < G between
      space groups. A procedure has been developed for the derivation of all subgroups
      U(j) < G which are obtained from U by a transformation with a translation (T
      equivalent subgroups). All T-equivalent supergroups G(k) > U can be determined in
      the same way from one supergroup G > U. The decisive group in this procedure is
      the translation part of the (Euclidean) normalizer of Hermann's group M. The
      group M is the uniquely determined group U < or = M < or = G with the
      translations of G and the point group of U. The method is particularly useful in
      the search for supergroups of space groups and is based on several lemmata which
      are formulated and proven in this paper. The results suggest under special
      conditions the possibility of a transition with 'region' formation in some
      analogy to the well known domain formation. This transition could occur from high
      symmetry to low symmetry or from low symmetry to high symmetry or even both ways.

PMID- 11326117
TI  - Location of Zn within the Mg12(LaxCe1-x) lattice by X-ray incoherent channelling
      patterns.
AB  - Systematic electron diffraction studies on intermetallic precipitates formed
      within a lightweight Mg-RE-Zn alloy (RE = La or Ce) identify these to be of
      structural type Mn(12)Th (space group I4/mmm). Analytical electron microscopy
      yields an overall composition of Mg(12)(La(x)Ce(1-x)) with x ~ 0.43, with 1 at.%
      Zn incorporated within the lattice. Variations in characteristic X-ray emission
      rates, as an electron beam is rocked near zone-axis orientations, are used to
      form two-dimensional channelling patterns, termed X-ray incoherent channelling
      patterns. This channelling contrast enables a specific sublattice site that is
      occupied by Zn to be unambiguously identified within the Mg(12)RE lattice. The
      particular sublattice site is denoted by the Wyckoff letter f, and is one of the
      three different Mg sublattice sites f, i and j. Of these three sites, the Wigner
      Seitz cell that is centred on the f sublattice site has the largest Mg-RE
      interatomic distance, and therefore the f site is expected to be favoured for
      accommodating the substitution of a larger Zn atom.

PMID- 11326118
TI  - Quasiperiodicity in decagonal phases forced by inclined net planes?
AB  - It is generally assumed that decagonal quasicrystals show periodically arranged
      atomic layers only on net planes perpendicular to the tenfold axis and
      quasiperiodically arranged ones parallel to it. However, there also do exist only
      slightly puckered atomic layers that are periodically arranged and inclined to
      the tenfold axis. They coincide with the net planes of the periodic average
      structures of the decagonal phase and are related to the strongest Bragg
      reflections. Since they link quasiperiodic and periodic directions, inclined net
      planes may play a crucial role for growth and stabilization of decagonal
      quasicrystals. In fact, it is shown how ideal quasiperiodic long-range order and
      inflation symmetry allow for the existence of inclined net planes with small
      corrugation and reinforce the relation with the periodic average structures.

PMID- 11326119
TI  - Phase determination via Sayre-type equations with anomalous-scattering data.
AB  - The necessary background for the analysis of complex-valued electron-density maps
      is established. Various systems of structure-factor equations of convolutional
      type akin to Sayre's squaring method equations are tested for agreement on the
      real and imaginary parts of the electron density as well as approximations
      thereof. A system of convolutional structure-factor equations holding in a
      complex-valued electron density generated by two atom types is developed. The
      scope of application of these equations is determined and it is shown that the
      equations provide a method of extrapolating high-resolution phases from a low
      resolution base phase set without introducing further model bias. Additional
      applications to phase refinement are explored.

PMID- 11326120
TI  - An evolutionary computational approach to the phase problem in macromolecular X
      ray crystallography.
AB  - The ab initio computation of the molecular envelopes of two proteins exclusively
      from their corresponding diffraction amplitudes demonstrates that an efficient
      and inherently parallel evolutionary search algorithm can assist in the direct
      phasing of macromolecules for which almost no a priori structural information is
      available. The applicability of this evolutionary computational approach is
      general and should not be limited to the examples described nor to extremes of
      data resolution, symmetry or structural size.

PMID- 11326121
TI  - Polarization-resolved output analysis of X-ray multiple-wave interaction.
AB  - The polarization suppression of the interfering components in X-ray multiple-wave
      interaction is observed for the first time by using a polarization analyzer with
      an arbitrary inclination of the diffraction plane with respect to that of the
      investigated crystal. The condition for total suppression of the multiple-wave
      interaction outside the investigated crystals by a polarization analyzer is
      derived theoretically from the modified Born approximation. By means of the
      partial suppression of the strong interfering component, the increase in the
      visibility of multiple-wave interference is experimentally and theoretically
      demonstrated. The proposed experimental polarization-resolved technique provides
      an operational way to enhance the visibility of X-ray multiple-wave interaction
      outside the investigated crystals for direct phase determination.

PMID- 11326122
TI  - Epidemiology of tick-borne encephalitis (TBE) and phylogenetic analysis of TBE
      viruses in Japan and Far Eastern Russia.
AB  - In Oshima, the southern part of Hokkaido, a tick-borne encephalitis (TBE) patient
      was found in 1993; in addition TBE virus was isolated from the blood samples of
      sentinel dogs, ticks pools, and rodents spleens in 1995 and 1996 by suckling
      mice. To identify when these TBE viruses emerged in Hokkaido, the times of
      divergence of TBE virus strains isolated in Oshima and Far Eastern Russia were
      estimated. TBE virus was isolated in Khabarovsk in 1998, and the nucleotide
      sequences of viral envelope protein genes of isolates from Oshima and Khabarovsk
      were compared. Based on the synonymous substitution rates of these virus E
      protein genes, the lineage-divergence times of these TBE virus strains were
      predicted phylogenetically to be approximately 260-430 years ago. Furthermore,
      the virulence of TBE virus isolates from Oshima and Khabarovsk were compared in a
      mouse model. The results showed that the isolates possessed very similar
      virulence in mice. European TBE vaccine was found to be effective in TBE virus,
      Hokkaido strain. This review provides evidence that the Oshima strains of TBE
      virus in Hokkaido emerged from the Far Eastern Russia a few hundred years ago,
      which explains why the virulence of these strains is similar to that of TBE
      viruses isolated in Russia. Practical application of the vaccine should be
      considered in Japan.

PMID- 11326123
TI  - Evaluation of the AMPLICOR CMV, COBAS AMPLICOR CMV monitor and antigenemia assay
      for cytomegalovirus disease.
AB  - The AMPLICOR CMV (qualitative DNA assay by PCR), COBAS AMPLICOR CMV Monitor
      (quantitative DNA assay by PCR), and antigenemia assay were tested for their
      ability to diagnose cytomegalovirus (CMV) infection in 115 immunocompromised
      patients. The AMPLICOR qualitative assay and the antigenemia assay were positive
      for all nine patients with a clinical diagnosis of CMV disease. The AMPLICOR
      quantitative assay was negative for one of the nine patients. In 106 patients
      without CMV disease, the AMPLICOR qualitative test was positive in 22, the
      quantitative test was positive in 23, and the antigenemia test was positive in 55
      patients. The AMPLICOR qualitative and quantitative assays had specificities of
      79% and 78% in patients without CMV disease, while that of the antigenemia assay
      was 48%. Diagnostic efficiencies were 79% for the AMPLICOR qualitative assay, 69%
      for the AMPLICOR quantitative assay, and 48% for the antigenemia assay. All three
      tests yielded positive results before, or at the same time as, the onset of CMV
      disease in most cases, which suggests they can be used to predict disease before
      the onset of symptoms. During antiviral treatment, test results tended to
      decrease quantitatively and finally became negative; negative results were
      followed by remission of symptoms. This suggests that the AMPLICOR quantitative
      assay and the antigenemia assay could be useful for monitoring therapeutic
      efficacy. The AMPLICOR qualitative and quantitative assays, as well as the
      antigenemia assay were considered effective for all of the following: diagnosing
      CMV disease, predicting the onset of disease, and evaluating the effectiveness of
      antiviral chemotherapy. The antigenemia assay was at times difficult to perform
      in the case of severely neutropenic patients, whereas the AMPLICOR assays could
      be used in such cases.

PMID- 11326124
TI  - Molecular and epidemiological study of the first outbreak of vanB type vancomycin
      resistant Enterococcus faecalis in Japan.
AB  - In July, 1999, an outbreak of vancomycin-resistant Enterococcus faecalis (VREF)
      with the vanB genotype occurred for the first time in Japan at Hokushin General
      Hospital, Nakano City, Nagano Prefecture. Four VREF strains were isolated from
      the clinical specimens of four inpatients, and 16 VREF strains were isolated by
      the screening of asymptomatic carriers and by surveillance of the hospital
      environment. All of the isolates possessed vanB genes. In a pulsed-field gel
      electrophoresis analysis, 19 out of 20 VREF isolates exhibited the
      indistinguishable restriction endonuclease digestion patterns of the chromosomal
      DNA. Additional investigation by Southern hybridization using the vanB probe
      implied that the vanB gene of these 19 isolates was encoded on a 110-kb plasmid.
      These findings indicate that the outbreak was principally caused by a single
      clone. The restriction endonuclease digestion patterns of the remaining single
      isolate was different from those of the other isolates. The vanB gene was encoded
      on the chromosome.

PMID- 11326126
TI  - Evaluation of the Japanese school health surveillance system for influenza.
AB  - In order to evaluate the Japanese nationwide school absenteeism surveillance
      system for pediatric influenza in comparison with the national sentinel
      surveillance for influenza, we used surveillance guidelines (Centers for Disease
      Control and Prevention, 1998) to determine the efficacy of the school health
      surveillance system (SHSS). Data regarding school absenteeism (age 4-15 years
      old) was compared with data regarding influenza-like illness (ILI) per sentinel
      sites during the second to the 11th weeks of 1998 and 1999. Despite the system's
      high simplicity and acceptability, telecommunication costs were estimated at US$
      490,000 (1998). Representativeness of schoolchildren was very accurate, but ILI
      for pre-school children (4-6 years) remained uncountable. Sensitivity,
      specificity, and positive predictive value of the SHSS compared to sentinel
      surveillance were calculated as 80%, 100%, and 100%, respectively (P=0.004).
      Although the SHSS was found to provide accurate surveillance data during periods
      of high influenza activity, non-influenza virus infections (e.g., adenovirus,
      rotavirus, and Norwalk virus, etc.) may become mixed in the SHSS data. Evaluation
      using this system should be continued employing a new case definition excluding
      gastrointestinal symptoms.

PMID- 11326125
TI  - Prevalence of Cryptosporidium parvum infections in weaned piglets and fattening
      porkers in Kanagawa Prefecture, Japan.
AB  - Fecal samples from 232 weaned piglets (1 and 3 months old) and 252 fattening
      porkers (6 months old) in 8 stock-raising farms located in Kanagawa Prefecture,
      Japan, from June 1998 to June 2000 were examined to determine the prevalence of
      Cryptosporidium infection. Detection of oocysts was performed using the ethyl
      acetate fecal concentration method and immunofluorescent staining. C. parvum
      oocysts were identified in 77 (33.2%) 1-3 months old weaned piglets from four
      farms. The odds of excreting among 1-3 months old piglets were more than 100
      times greater than among 6 months old porkers (95% confidence interval: 17-902).
      This strongly suggests that weaned piglets are important reservoirs of pathogenic
      microbes whose potential contamination of drinking water has epidemiological
      implications for human health.

PMID- 11326127
TI  - Rate of subclinical hepatitis A virus infection in adult HIV-1-infected patients.

PMID- 11326128
TI  - The optimal molar ratio between binding-deficient and fusion-deficient murine
      leukemia virus envelope proteins for complementation to induce syncytia.

PMID- 11326129
TI  - Clinical study of mutans streptococci using 3DS and monoclonal antibodies.

PMID- 11326130
TI  - The isolation of human parechovirus 1 from cases of acute respiratory illness in
      children.

PMID- 11326131
TI  - Phylogenetic analysis of Salmonella enteritidis isolates from food poisonings
      using pulsed-field gel electrophoresis over the period of June 1997 to December
      2000 in Hyogo Prefecture.

PMID- 11326132
TI  - Phylogenetic analysis of genotyptic variations of Salmonella enteritidis isolates
      from sporadic infections using pulsed-field gel electrophoresis from December
      1996 to November 2000 in Hyogo Prefecture.

PMID- 11326133
TI  - Mutans streptococci and Lactobacillus as risk factors for dental caries in 12
      year-old children.

PMID- 11326134
TI  - Sylvian fissure asymmetries in nonhuman primates revisited: a comparative mri
      study.
AB  - Magnetic resonance images (MRI) were collected in a sample of 28 apes, 16 Old
      World monkeys and 8 New World monkeys. The length of the sylvian fissure (SF) and
      the superior temporal sulcus (STS) was traced in each hemisphere from three
      regions of the cerebral cortex. These three regions were labeled according to
      their position on the sagittal plane as lateral, medial and insular. It was
      hypothesized that the length and asymmetry of these fissures would be dependent
      on the region of measurement and that a leftward asymmetry in the SF and STS
      would be more robust in the great ape sample than for the monkeys. The results
      indicated within the ape sample a population-level leftward asymmetry in the
      medial and insular regions of the SF. Within the Old and New World monkey
      samples, the SF was leftward in the medial region at the population level, but
      not at the insular region. Additionally, the Old World monkeys exhibited a
      population-level rightward lateral SF and a rightward lateral STS. No other
      families exhibited population-level asymmetries in the lateral region of the SF
      or in any region of the STS. These results are consistent with findings reported
      in apes and, to a lesser extent, monkeys. MRI has excellent potential for
      comparing neuroanatomy across taxonomic families that will help future
      investigations.

PMID- 11326135
TI  - Emergence of axonal tracts in the developing brain of the turbot (Psetta maxima).
AB  - In this study we have investigated the pattern of morphogenesis and axogenesis in
      the turbot brain during embryonic and early larval stages with
      immunohistochemistry using an antibody against acetylated tubulin. The first
      immunoreactive elements were detected at 74 h post-fertilization in fibers
      running in the medial and lateral longitudinal fascicles. Newly positive axonal
      bundles are progressively added during development forming rostrocaudally
      directed tracts. The tract of the postoptic commissure appears at 86 h post
      fertilization located rostrally to the medial longitudinal fascicle. Together,
      the medial longitudinal fascicle and the tract of the postoptic commissure
      constitute a major longitudinal axonal pathway, which is extended rostrally in
      embryos of 98 h post-fertilization by the supraoptic tract. In the forebrain, two
      vertical tracts, the tract of the posterior commissure (appearing around 98 h
      post-fertilization) and the tract of the anterior commissure (detected at 110 h
      post-fertilization) project descending axons to the pre-existing axonal
      longitudinal pathway. These early tracts are connected by four associated
      commissures (ventral tegmental, postoptic, posterior and anterior commissure).
      Some groups of labeled cell bodies are identified either as the origin of the
      embryonic tracts or contributing axons to the axonal pathways. Additionally, a
      conspicuous cluster of large cells, not clearly associated with any axonal
      bundle, was observed from 98 h post-fertilization lining the caudal floor of the
      presumptive hypothalamus. Several hypotheses are proposed to determine the nature
      of these cells. A comparison of the emergence of the axonal circuitry in turbot
      and that of other teleosts reveals significant analogies, suggesting that a
      common pattern underlies the establishment of the embryonic tracts in this
      vertebrate group. The minor differences observed between different teleost
      species, associated with the absence of some axonal fascicles, is also
      considered.

PMID- 11326137
TI  - Distribution pattern of taste buds along hyoidal barbels of Mullus barbatus and
      M. surmuletus.
AB  - The external taste buds of bony fishes are differentiated and grouped throughout
      the body epithelium, concentrating in the buccopharyngeal cavity or in certain
      external organs such as the lips, barbels or fins. The family Mullidae
      (goatfishes) is characterized by having barbels covered with taste buds (TBs).
      However, It is not known how the TBs are distributed and how their
      characteristics vary along the barbels. To obtain answers to these questions, the
      morphological variability in taste bud density (deltaTB), pore area (A(P)) and
      taste bud area (A(TB)) was studied in Mullus barbatus (L., 1758) (red mullet) and
      M. surmuletus (L., 1758) (striped red mullet), for fish ranging in size from 58
      to 227 and from 56 to 287 mm in total length (L(T)), respectively. Assuming that
      larger fish are older, in both species the pore area (A(P)) and taste bud area
      (A(TB)) increased with ontogenic development. Also, in both species clear
      differences were observed along the barbel. The delta(TB) increased from the
      basal area to the apical area, whereas both the A(P) and A(TB) had an inverse
      pattern.

PMID- 11326136
TI  - Proliferation zones in the adult brain of a sequential hermaphrodite teleost
      species (Sparus aurata).
AB  - Teleost sex change is an important model to understand general principles of
      sexual differentiation and plasticity in the adult brain. The present study is
      the first to examine the proliferation zones in the adult brain of males, females
      and sex-changing individuals of a protandrous teleost species (Sparus aurata), by
      means of 5-bromo-2-deoxyuridine immunocytochemistry. Postnatal neurogenesis in
      the marine teleost brain was found in ventricular and subventricular areas of the
      brain that in most cases coincided with the embryonic proliferation zones. The
      molecular layer of corpus and valvula cerebelli exhibited the highest mitotic
      activity in the adult brain. High mitotic activity was observed in the
      hypothalamic, thalamic and telencephalic ventricular areas, as well as the dorsal
      and ventral rim of the optic tectum. Most of the labeled cells were elongated,
      indicating the initiation of migratory activity. There were no qualitative
      differences in the distribution of proliferation zones between the sex phases
      studied with the exception of the ventricular region of the dorsal hypothalamic
      area. Volume fraction analysis of the area occupied by the labeled cells
      suggested that this region included higher densities of newborn cells in the
      female animals. The proliferation pattern in the adult gilthead sea bream brain
      is in agreement with the hypothesis of the continuous generation of new cells in
      the teleost brain. Moreover, our data propose that cell proliferation differences
      possibly existing in the ventricular region of the dorsal hypothalamus between
      sexual phases, might be involved in central mechanisms of sexual plasticity in
      protandrous hermaphrodite teleosts.

PMID- 11326139
TI  - Sun shades and eye size in birds.
AB  - Visual field width above the head is significantly correlated (r(s) = 0.92, n =
      11, p < 0.001) with eye size in a sample of terrestrial birds that differ in
      their phylogeny and ecology. These species can be divided into two groups.
      Smaller-eyed sun-observers (axial length <18 mm) have comprehensive or near
      comprehensive visual coverage of the celestial hemisphere and are thus unable to
      avoid viewing the sun. Larger-eyed sun-avoiders (axial length >18 mm) have
      restricted visual fields and various types of optical adnexa (enlarged brows,
      hair like feathers on the eye lids and around the eye) which can prevent solar
      illumination of the cornea. We suggest that these differences relate to visual
      rather than pathological problems and argue that the reduction of disability
      glare, produced by sunlight falling directly upon the eye, becomes increasingly
      significant as eye size increases. We propose that the reduced visual fields and
      optical adnexa of the larger-eyed birds are primarily concerned with the
      maintenance of high spatial resolution.

PMID- 11326138
TI  - A comparative study of protein kinase C-like immunoreactive cells in the retina.
AB  - The present study is a morphological and quantitative analysis of protein kinase
      C-like immunoreactive (PKC-L ir) bipolar cells in the retinas of five different
      vertebrate species (chicken, tench, zebrafish, goldfish and rat). The morphology
      of PKC-L-ir bipolar cell axon terminals in fish differs significantly from those
      of chicken and rat retinas. Fish have bulky terminals whereas chicken and rat
      have their terminals in the form of small knob-shaped branches. In tench and
      goldfish, PKC-L-ir bipolar cells gradually decrease in size from the medial
      (i.e., in tench: mean +/- SD soma area of 30.09 +/- 5.98 microm2) to the
      peripheral (i.e., in tench: 19.93 +/- 1.73 microm2) retinal regions. This is not
      observed in chicken, rat or zebrafish where there is more homogeneity in s oma
      and axon terminal sizes between different retinal regions. Except in chicken,
      cell density increases from the central (i.e., in tench: mean +/- SD 1795.88 +/-
      242.35 cells/mm2) to the peripheral (i.e., in tench: 4295.41 +/- 279.23
      cells/mm2) retina. This study provides data that show relevant differences in the
      PKC-L-ir bipolar morphology and density among birds, fish and mammals. Moreover,
      these structural variations could mean not only differences in the cellular
      physiology, but also in the patterns of development and maintenance of the retina
      in each species.

PMID- 11326140
TI  - Assessment of pseudohypertrophy as a measure of left-ventricular compression in
      patients with cardiac tamponade.
AB  - BACKGROUND: Left-ventricular pseudohypertrophy reflecting left-ventricular
      compression was reported in a selected group of patients with cardiac tamponade.
      HYPOTHESIS: Criteria for the presence of pseudohypertrophy can be established to
      guide its use as a sign of left-ventricular compression in patients with cardiac
      tamponade. METHODS: Left-ventricular wall thickness, diameters, relative
      diastolic wall thickness (%) = (posterior wall thickness/end diastolic radius) x
      100 and estimated left-ventricular mass were measured in patients with small,
      moderate and large pericardial effusion, in patients with cardiac tamponade
      before and after pericardiocentesis (16 patients in each group) and in 30 control
      subjects with normal echocardiograms. RESULTS: Left-ventricular posterior wall
      thickness was increased (12 +/- 2 vs. 9 +/- 1 mm, p < 0.001), left-ventricular
      end-diastolic diameter was reduced (3.9 +/- 0.5 vs. 4.6 +/- 0.3 cm, p < 0.001)
      and relative left-ventricular diastolic wall thickness was increased (61 +/- 13
      vs. 41 +/- 4.5%, p < 0.001) only in patients with cardiac tamponade compared to
      controls, but not in patients with small, moderate and large effusions,
      respectively (relative wall thickness: 42 +/- 5, 41 +/- 7 and 44 +/- 7%, p = NS).
      Mean values of the estimated left-ventricular mass were similar in all groups.
      Following pericardiocentesis all parameters were normal. CONCLUSIONS: Despite
      normal left-ventricular mass, relative left-ventricular diastolic wall thickness
      is elevated in patients with cardiac tamponade. In contrast it is normal in
      patients with various degrees of pericardial effusion supporting its use as a
      quantitative measure of left-ventricular compression in patients with suspected
      cardiac tamponade.

PMID- 11326141
TI  - Prognostic value of antibody titre to heat-shock protein 65 on cardiovascular
      events.
AB  - Accumulating evidence suggests that the immune system is involved in
      atherogenesis, such as the correlation of the antibody titre to heat shock
      protein (hsp) with atherosclerotic lesions in the carotid and coronary arteries.
      Because the prognostic value of the hsp antibody titre for future cardiovascular
      events has not been evaluated until now, we performed a follow-up study on 195
      subjects without a history of established cardiovascular risk factors (e.g.
      hypercholesterolaemia, diabetes, smoking), recruited for hsp antibody titre
      determination in 1995. Cardiovascular events were defined as unstable angina with
      the need for hospitalisation, myocardial infarction, re-vascularisation (PTCA,
      bypass), stroke and cardiovascular death. Among 79 men with coronary artery
      disease defined by coronary angiography, hsp antibody titres were significantly
      higher in those with future cardiovascular events (467.0 +/- 56.3) than in
      patients without further events (351.0 +/- 23.3; p < 0.049). Because anti-hsp
      antibody titres might be of prognostic value for coronary artery disease,
      patients with an increased hsp antibody titre should obtain intensive management
      of classical risk factors.

PMID- 11326142
TI  - Familial idiopathic dilatation of the right atrium with complete atrio
      ventricular block: a new syndrome?
AB  - Familial occurrence of idiopathic dilatation of the right atrium is extremely
      rare. This is the first description of a family in which 2 siblings had a
      syndrome of idiopathic dilatation of the right atrium associated with complete
      atrio-ventricular block. The family workup did not show other family members to
      be affected, and the question we raise is whether or not this might be a new
      syndrome.

PMID- 11326143
TI  - Reduced concentrations of soluble adhesion molecules after antioxidant
      supplementation in postmenopausal women with high cardiovascular risk profiles--a
      randomized double-blind study.
AB  - BACKGROUND: One of the suggested mechanisms of increased cardiovascular risk in
      postmenopause is a loss of the antioxidant effects of estrogens. It has been
      shown that classical cardiovascular risk factors increase oxidative stress on the
      arterial wall, and that endothelial cells react to this insult by increased
      expression of cellular adhesion molecules (CAM), which in turn are markers of
      arterial wall inflammation. METHODS: A randomized, placebo-controlled, double
      blind study was performed in 60 postmenopausal women with high cardiovascular
      risk profiles, but free from clinical atherosclerotic disease. Patients were
      randomized to either antioxidant supplementation (using a combination of natural
      antioxidants; n = 30) or placebo (n = 30), and followed for 12 weeks. The
      concentrations of the adhesion molecules sVCAM-1 and sICAM-1 were measured by
      ELISA at baseline and at the end of the study, as well as total cholesterol, LDL,
      HDL, triglycerides and blood pressure. RESULTS: 27 women in the antioxidant
      supplementation group and 29 on placebo completed the study. At baseline, there
      were no significant differences in measured parameters between the groups: sICAM
      1 concentrations were 341.8 +/- 116.9 vs. 349.9 +/- 104.6 ng/ml (active treatment
      vs. placebo; p = n.s.) and sVCAM-1 concentrations were 780.5 +/- 325.8 vs. 761.0
      +/- 333.7 ng/ml (p = n.s.). In contrast, at the end of the study, sICAM-1
      concentrations were 301.6 +/- 56.0 vs. 356.0 +/- 134.8 ng/ml (active treatment
      vs. placebo; p = 0.053) and sVCAM-1 concentrations were 656.0 +/- 326.5 vs. 818.5
      +/- 381.0 ng/ml (p = 0.04). There were no significant differences between or
      changes within the groups in measured cholesterol and blood pressure. CONCLUSION:
      Antioxidant supplementation reduces serum concentrations of endothelium-derived
      adhesion molecules sICAM-1 and sVCAM-1 in postmenopausal women with high
      cardiovascular risk profiles.

PMID- 11326144
TI  - New technique for simultaneous catheter mapping of pulmonary veins for catheter
      ablation in focal atrial fibrillation.
AB  - INTRODUCTION: Most focal atrial fibrillation (AF) can be triggered by premature
      beats from pulmonary veins (PVs), and ablation of these foci could cure AF.
      However, it is difficult to locate the trigger points of PVs using only one
      mapping catheter. The purpose of the present study was to investigate the
      efficacy of using four mapping catheters in four PVs simultaneously in the
      ablation of focal AF. METHODS AND RESULTS: Thirty-two patients with frequent
      attacks of paroxysmal AF triggered by PV foci were included. After a transseptal
      procedure, three 2-french microcatheters and one 7-french catheter for ablation
      were placed into each of the PVs, and mapping of the four PVs was performed
      simultaneously. Fifty-eight foci were identified; 51 triggers (88%) originated
      from the PV and 7 (12%) from atrial tissue. The trigger points of AF were found
      in a single focus in 14 patients, in 2 foci in 12 patients, and in 3-4 foci in 6
      patients. During a mean follow-up period of 10 +/- 4 months, ablation eliminated
      AF without drugs in 86, 50 and 33% of the patients with 1, 2 and 3-4 targeted
      PVs, respectively; 20 patients (63%) were successfully ablated. Age, history of
      AF, the dimension of the left atrium and the number of focal origins were
      significant predictors of success. CONCLUSION: The technique of simultaneous
      mapping of PVs using quadruple catheters is a feasible and effective method for
      mapping the trigger points and ablation of focal AF originating from PVs.

PMID- 11326145
TI  - Effect of ascorbic acid on endothelial dysfunction of epicardial coronary
      arteries in chronic smokers assessed by cold pressor testing.
AB  - BACKGROUND: In chronic smokers there is evidence for increased formation of
      oxygen-derived free radicals within the vessel wall impairing endothelial
      function. It has been suggested that the inactivation of endothelium-derived
      nitric oxide by oxygen free radicals contributes to endothelial dysfunction.
      Hence, we tested the hypothesis that in chronic smokers the antioxidant ascorbic
      acid could improve abnormal endothelial function of epicardial coronary arteries.
      METHODS AND RESULTS: Thirty-one patients (mean age 57 +/- 9 years) referred for
      routine diagnostic catheterization for evaluation of chest pain and without
      angiographically significant coronary artery stenoses were randomly assigned to
      one of the study groups to assess vasomotor response of epicardial coronary
      arteries due to cold pressor testing (CPT) before and after intravenous infusion
      of 3 g of ascorbic acid or 100 ml x 0.9% saline infusion. In 6 controls (mean age
      55 +/- 3 years) CPT led to a similar increase in luminal area before and after
      ascorbic acid administration (26.5 +/- 15.0 vs. 28.4 +/- 17.7%, p = NS). In 15
      chronic smokers (mean age 55 +/- 9 years), CPT induced a decrease in the luminal
      area of -18.5 +/- 6.3%. This flow-dependent vasoconstriction was significantly
      reversed to 7.7 +/- 6.2% (p < or = 0.03) vasodilation after intravenous ascorbic
      acid administration. In 10 chronic smokers (mean age 57 +/- 11 years) saline
      infusion (placebo) did not have a significant effect on CPT-induced
      vasoconstriction (-12.7 +/- 5.1 vs. -13.1 +/- 5.1%, p = NS). The CPT-induced
      increase in luminal area in chronic smokers after ascorbic acid infusion was
      significant compared to controls and placebo (each p < or = 0.05). Our assessment
      of endothelium-independent responses to nitroglycerin revealed no significant
      differences between the single study groups (p = NS). CONCLUSION: In chronic
      smokers acute intravenous administration of ascorbic acid significantly improves
      CPT-induced coronary endothelium-dependent dysfunction. According to the current
      understanding, this effect is due to improved cellular redox imbalance and
      prevention of nitric oxide inactivation in the endothelium and subendothelial
      space.

PMID- 11326146
TI  - High cardiac angiotensin-II-forming activity in infarcted and non-infarcted human
      myocardium.
AB  - The aims of this study were to compare human cardiac angiotensin-II-forming
      activity (AIIFA) between the intact area of control autopsy hearts without
      cardiac disease (n = 10) and the infarcted or non-infarcted area of autopsy
      hearts with myocardial infarction (MI, n = 7) and to determine responsible
      angiotensin-II-forming enzymes. Cardiac total and chymase-dependent AIIFAs were
      significantly higher in the infarcted and non-infarcted myocardium than those in
      non-MI heart, while angiotensin-converting enzyme-dependent AIIFA increased only
      in the infarcted myocardium. The density of chymase antibody-positive mast cells
      in the non-infarcted area of MI heart correlated positively with total or chymase
      dependent AIIFA. Augmented AIIFA was also detected in the left atrium of post-MI
      hearts. Our results indicated that cardiac angiotensin II formation could be
      activated in the infarcted as well as in non-infarcted myocardium of the post-MI
      human heart.

PMID- 11326147
TI  - Biochemical markers of ischaemia for the early identification of acute myocardial
      infarction without St segment elevation.
AB  - Blood was collected on admission and after 1-2 h in 130 consecutive patients
      admitted with typical chest pain in order to assess the capacity of myoglobin,
      fatty-acid-binding protein (FABP), CK-MB mass, and troponin I (TnI) in the early
      identification of acute myocardial infarction (AMI) without ST elevation. Using
      the maximum value within 6 h of onset of symptoms, AMI was detected with a 90-95%
      sensitivity and a 81-94% specificity by FABP at a cut-off level 8-12 midrog/l, or
      81-86% and 89-93%, respectively, by myoglobin at a cut-off level 70-90 microg/l.
      CK-MB mass and TnI had low sensitivity, albeit very high specificity. As almost
      all AMI patients were identified within 6 h, serial measurements of FABP or
      myoglobin ruled out AMI with a very high degree of certainty. Due to the low
      prevalence of AMI (16%), the positive predictive values were modest (47-73%), yet
      increasing the probability of AMI by a factor 3-4. Myoglobin and FABP are very
      useful markers in the early triage of chest pain patients.

PMID- 11326148
TI  - Coronary collateral flow and hypertensive response in the exercise test.

PMID- 11326149
TI  - Role of selective coronary arteriography in patients with cardiac myxoma.

PMID- 11326150
TI  - An analytical triad for the diagnosis of pulmonary embolism.

PMID- 11326151
TI  - Systemic tetrahydrobiopterin (BH4) levels and coronary artery disease.

PMID- 11326152
TI  - Different course of heart rate in patients with coronary heart disease during
      standardized ergometry compared to healthy controls.

PMID- 11326153
TI  - [Does the increasing cesarean section rate reflect a shift in indications or a
      decline in quality?].
AB  - The cesarean section rate is continuously increasing at our department, from 13.8
      to 17.2% between 1999 and 2000. The mother's wishes regarding the mode of
      delivery weigh increasingly on our obstetric decisions. Patient acceptance of
      elective cesarean section is high, and the increasing cesarean section rate is
      influenced by paramedical factors. Obstetrics appears to be developing into a
      mostly surgical discipline. The effect this has on quality (and costs) remains to
      be seen.

PMID- 11326154
TI  - [Psychological aspects of ultrasound examinations during pregnancy].
AB  - The acceptability of ultrasound examinations during pregnancy has been documented
      in many studies. Yet there is little empirical evidence for the postulated
      psychological benefits of ultrasound examinations. Although seeing the baby is
      most often rated as a moving experience, there are no proven long-term effects of
      ultrasound visualization on bonding with the fetus or on pregnant women's health
      related maternal behaviour. There is evidence to support the notion that
      attenuated anxiety and stress immediately following the examination are likely
      artefactual - a reflection of increased anxiety before real-time scan. Review of
      the literature indicates no evidence as to whether antenatal detection of fetal
      abnormalities leads to improvement in coping or only prolongs the phase of
      psychological stress and mourning. This articles provides an overview of current
      research on psychological effects of prenatal ultrasound examination.

PMID- 11326155
TI  - [Frequency of cesarean sections in Austria].
AB  - OBJECTIVE: While there exist detailed reports on the frequency of cesarean
      sections in many European countries, there are only selective data of single
      centers available in Austria. Thus this study aims at evaluating the present
      frequency of cesarean sections in Austria. METHODS: To achieve this aim, we
      analyzed all births during the years 1996 (n = 89,208), 1997 (n = 84,408) and
      1998 (n = 81,568). Along with the general mean rate of sections, we also describe
      the influences of the duration of pregnancy, of the birth weight, and of the
      number of paturitions. The data were statistically evaluated by chi-square test.
      RESULTS: During the study period, the frequence of sections rose from 13.08%
      (1996) to 14.0% (1997) and to 14.55% (1998). This rise proved to be statistically
      significant (p = 0.0001). 47% of premature births (< or = 35th week of gestation)
      are delivered by cesarean section. This rate drops to only 13.24% after the 35th
      week of gestation. Yet, more than half of pregnancies with dystrophic children
      (<2,000 g) are delivered by cesarean section even after the 35th week of
      gestation. Primigravidae have to expect section in 17% of the cases (1998); the
      section rate diminishes continuously, however, with increasing number of
      pregnancies. CONCLUSIONS: Following the general trend, the frequency of cesarean
      sections is continuously rising in Austria too. The present study can serve as a
      basis for international comparisons as well as for measures of intradepartmental
      quality control.

PMID- 11326156
TI  - [Effect of repetitive prenatal corticosteroid medication on intrauterine growth
      and growth in early childhood].
AB  - OBJECTIVE: The evaluation of the effects of repeated antenatal corticosteriod
      (CS) medication on birth size and size at the age of 4 years. METHODS: 82
      children exposed to CS initially between 26 and 28 weeks of gestation were
      matched with 82 controls of the same gestational age and sex. RESULTS: No
      differences were observed between the CS and control groups with regard to
      weight, head circumference, and length at birth and at the age of 4 years.
      CONCLUSIONS: Our study failed to demonstrate that repetitive antenatal medication
      with CS in order to induce lung maturation has a negative impact on intrauterine
      growth and growth in early childhood.

PMID- 11326157
TI  - [Screening of Chlamydia trachomatis: is the diagnostic efficacy good enough?].
AB  - OBJECTIVE: In the background of discrepant results of C. trachomatis testing in
      women with suspected genital infections, three different tests have been
      compared. METHOD: 594 endocervical swabs were collected from women visiting the
      family planning clinic in Aarau. Each of the following tests was evaluated: Cobas
      Amplicor Chlamydia trachomatis, IF Chlamyset, and Chlamydia IF direct. If one of
      these three tests was positive, the fixed material on the slides was scraped off,
      and a PCR was performed. RESULTS: 15 out of 594 samples were "true'-positive. PCR
      recognized 14 of them, the IF Chlamyset 13, and the Chlamydia IF 8. With the IF
      Chlamyset 37 samples were false-positive. CONCLUSIONS: PCR testing exhibits a
      good sensitivity and a high specificity, but we think that the sensitivity can be
      increased by improving the sample preparation step. The Chlamydia IF direct has a
      good specificity, but a rather low sensitivity. It should be noted that the PCR
      has the potential to become a new gold standard for the detection of C.
      trachomatis.

PMID- 11326158
TI  - [Bone marrow involvement in ovarian cancer determined by immunohistochemical
      methods].
AB  - Atypical epithelial cells in the bone marrow of patients with ovarian cancer were
      evaluated using immunohistochemical techniques. We investigated cytospin
      preparations of bone marrow taken from 9 women with benign ovarian tumors and 59
      women with malignant ovarian tumors. Two monoclonal antibodies (NCL-C11 and NCL
      CA 125) were used. With both antibodies we were able to detect keratin and CA 125
      antigen expression in the bone marrow of 9 (18.4%) of the patients with ovarian
      cancer. With regard to the wide histological differentiation of ovarian
      carcinomas, the presence of atypical epithelial cells in the bone marrow was
      required as a prognostic factor for survival and relapses. This should be
      investigated in a larger study group.

PMID- 11326159
TI  - [Retrospective analysis of dose intensity of epirubicin in breast cancer].
AB  - OBJECTIVE: In breast cancer the efficacy of epirubicin-based chemotherapy is
      possibly related to the actual dose intensity applied. We retrospectively
      determined the administered dose intensity and the relative toxicity and efficacy
      of an epirubicin-containing regimen in patients with primary or metastatic breast
      cancer. PATIENTS AND METHODS: Fluorouracil, epirubicin, and cyclophosphamide
      (FEC) were either given at a standard dose of 500/50/500 mg/m2 (FE50C) or at an
      intensified dose of 500/75/500 mg/m2 (FE75C) every 3 weeks. Of the 66 patients
      treated, 63 were evaluable; 43 had metastatic breast cancer, and 20 patients with
      an increased risk of relapse received FEC as an adjuvant treatment. RESULTS: Dose
      intensity and absolute dose of adjuvant treatment were 81 and 70% for FE50C and
      96 and 88% for FE75C. In metastatic breast cancer, the dose intensity for FE50C
      was 94% and for FE75C 92%. In a retrospective comparison, the 4-year overall
      survival following adjuvant FE50C and FE75C was 40 and 48%, respectively (p =
      0.47). The dose intensification led to a higher response rate of 34 vs. 44%.
      There were no significant differences in response duration and survival time. The
      toxicity profiles were comparable between FE50C and FE75C. CONCLUSIONS: In
      general, the doses applied were lower than initially planned. Higher doses of
      epirubicin did not result in a significant increase of toxicity. Despite the
      limitations of a retrospective analysis, our observations support the importance
      of adherence to the planned dose intensity as a prerequisite for optimal
      treatment of patients suffering from breast cancer. As our results could be
      related to selection bias, dose-intensified anthracycline-containing regimens
      should be further evaluated in prospective trials.

PMID- 11326160
TI  - [Efficacy and safety of two cephalosporins in the perioperative prophylaxis in
      patients undergoing abdominal or vaginal hysterectomies or gynaecological
      laparotomies: a prospective randomized study].
AB  - The aim of this study was to compare efficacy and safety of perioperative
      antibiotic prophylaxis in patients undergoing abdominal or vaginal hysterectomy
      or gynaecological laparotomy to improve the prevention of surgical wound
      infections. One hundred and ninety-nine patients were prospectively randomized
      into two groups: the first group (n = 100) received perioperative prophylaxis
      using 1 g cefotiam (Spizef) and 0.5 g metronidazole (Clont) intravenously 30 min
      before surgery, whereas the second group (n = 99) was treated with 2 g cefoxitin
      (Mefoxitin) intravenously, also 30 min before surgery. The efficacy of the
      perioperative antibiotic prophylaxis was assessed clinically and on the basis of
      laboratory parameters. No wound infections were observed in 97 patients (97%) of
      the cefotiam-treated group and in 94 patients (94%) of the cefoxitin-treated
      group. No systemic postoperative infections were observed in 81% of the patients
      treated with cefotiam combined with metronidazole and in 85% of the patients
      treated with cefoxitin. The good tolerability of the drugs administered was
      proven in 98% of the patients treated with cefotiam and metronidazole and in 97%
      of the patients treated with cefoxitin. In both groups 3 patients developed
      nausea and/or vomiting, respectively, due to the antibiotic prophylaxis. A low
      infection rate after gynaecological surgery was observed. Cefotiam as a low
      dosage combined with metronidazole was as effective as cefoxitin. Cephalosporins
      of the second generation in combination with metronidazole can, therefore, be
      considered effective and safe drugs in the prevention of postsurgical infections.

PMID- 11326161
TI  - [Conservative treatment of ectopic pregnancies and presentation of a complicated
      case of peritonitis due to methotrexate].
AB  - Due to the improvement of diagnostic procedures and the refinement of endoscopic
      methods, the treatment of ectopic pregnancy has more and more turned against
      salpingectomy and towards organ-preserving actions. Moreover, for some years a
      range of medical therapies has been offering an alternative to surgical
      intervention. In addition to presenting a review of conservative methods of
      treatment, we report on a patient with an angular pregnancy who was treated with
      methotrexate and developed a pronounced peritonitis.

PMID- 11326162
TI  - [Vaginal bleeding and premature contractions during pregnancy in uterus bicornis
      with expulsion of a decidual polyp].
AB  - Diagnosis and clinical course of a rare case are described, and the importance of
      prenatal ultrasound diagnostic is discussed.

PMID- 11326163
TI  - Obstetric litigation: effects on clinical practice.
AB  - Many claims concerning extent and consequences of litigation have been made,
      despite a lack of comprehensive and widely available data. It has been suggested
      that a rapidly increasing rate of litigation has caused problems in the
      recruitment and retention of obstetricians, and has also caused practitioners to
      practice 'defensively'. This article discusses meaning and significance of
      defensiveness within obstetrics and midwifery and quantifies the incidence of
      certain examples of defensive practice. Based on large-scale postal surveys of
      obstetricians and midwives in Scotland and England, as well as follow-up
      interviews, it clarifies the significance of what has become known as defensive
      medicine in maternity care, notably in relation to caesarean sections. It then
      examines the role of clinical risk management, and the growth of protocols and
      guidelines in particular, in trying to limit litigation.

PMID- 11326164
TI  - [Recommendations for oral contraception. 24th meeting of the "Zurich Discussion
      Circle"]].

PMID- 11326165
TI  - The geriatric cancer patient: equal benefit from equal treatment.

PMID- 11326166
TI  - Clinically localized prostate cancer: the paradox of paradoxes.

PMID- 11326167
TI  - Prostate cancer: screening and early detection.
AB  - BACKGROUND: Despite more than a decade of prostate-specific antigen (PSA)-based
      screening, the proven impact of screening on mortality due to prostate cancer
      continues to be controversial. METHODS: A literature review of issues pertaining
      to the epidemiology, screening, early detection, and mortality as they relate to
      prostate cancer was conducted. Included in the review are PSA refinements,
      controversies of screening, and organization guidelines. Finally, recent reports
      of mortality rates in the post-PSA era are presented for discussion. RESULTS:
      Prostate cancer mortality rates have begun to decline for the first time since
      statistics have been recorded. The recent decline in age-adjusted mortality rates
      from prostate cancer is significant, and this decline appears to be earlier than
      would have been predicted. This finding, coupled with the dramatic decline in
      metastatic disease, implies that PSA-based screening may be responsible for a
      significant portion of this improvement in mortality. CONCLUSIONS: The cost of
      prostate cancer screening appears to be acceptable. Randomized studies of PSA
      based screening are currently ongoing, although the results may not be available
      for a decade. Currently, the best evidence is derived from population-based
      studies that appear to show a benefit to prostate cancer screening.

PMID- 11326168
TI  - Transrectal ultrasound and biopsy in the early diagnosis of prostate cancer.
AB  - BACKGROUND: Historically, the prostate was evaluated for cancer by simple digital
      rectal examination, and biopsy to obtain a tissue diagnosis of cancer was
      performed blindly. The advent of ultrasound technology offered a new way to
      evaluate the prostate, and biopsy techniques were soon developed to incorporate
      ultrasound guidance. METHODS: The authors review the role of transrectal
      ultrasound (TRUS) of the prostate and ultrasound-guided biopsy of the prostate in
      the diagnosis of prostate cancer. These techniques are traced from their origins
      to the current standards of care, with attention paid to developments and
      controversies in recent literature. RESULTS: Early experience with TRUS led to
      the description of "classic" sonographic findings of prostate cancer. To obtain a
      tissue diagnosis of cancer, these regions were initially targeted in ultrasound
      guided biopsies. Concomitant with the development of TRUS, though, was the
      development of the prostate-specific antigen (PSA) assay. Over the past decade,
      there has been a profound stage migration due to earlier detection of prostate
      cancer. Most patients now diagnosed with prostate cancer have no palpable
      abnormality or specific sonographic findings. In response, ultrasound-guided
      biopsies have become more systematic, rather than lesion-specific, in nature.
      CONCLUSIONS: TRUS continues to play an important role in the evaluation of the
      prostate when malignancy is suspected. Although the optimal method of prostate
      biopsy is controversial, ultrasound is critical in ensuring accurate sampling of
      the gland.

PMID- 11326169
TI  - Observation in the management of localized prostate cancer.

PMID- 11326170
TI  - Neoadjuvant androgen ablation in localized carcinoma of the prostate.
AB  - BACKGROUND: An increased awareness of prostate cancer has led to a rise in the
      detection of this disease at a clinically localized stage at presentation. This
      article discusses the role of neoadjuvant hormonal ablation at this earlier stage
      to decrease tumor bulk and thus enhance survival. METHODS: Outcomes from each
      primary modality for localized treatment of prostate cancer with and without
      neoadjuvant androgen deprivation (NAAD) are reviewed. RESULTS: Survival benefit
      using NAAD has not yet been demonstrated from prostatectomy. Long-term hormonal
      deprivation provides an improved time to progression and has decreased distant
      metastatic and biochemical failure for poor-risk patients undergoing external
      beam radiation. The toxicities of brachytherapy can be decreased with NAAD.
      CONCLUSIONS: NAAD with radical prostatectomy is considered to be investigational.
      The duration of NAAD needs to be delineated for poor-prognosis patients who are
      treated with external-beam radiation therapy, but the approach improves the local
      toxicity of brachytherapy.

PMID- 11326171
TI  - The evolving role of prostate brachytherapy.
AB  - BACKGROUND: The publication of several large studies with long-term results on
      the use of prostate brachytherapy has resulted in increased use of this option
      for patients with localized prostate cancer. METHODS: A historical review of
      brachytherapy as an approach to prostate cancer management is provided, as well
      as a general summary of the implant technique and the results to date according
      to patient risk. The effects of combination therapies for specific patient groups
      are also reviewed. RESULTS: A recent 12-year follow-up reported no failures after
      10 years, and 75% of recurrences occurred with-in the first 5 years. Patients at
      low risk for failure based on stage, grade, and prostate-specific antigen (PSA)
      parameters are likely to have disease confined to the prostate. Those with more
      advanced disease are likely to have a lower probability of cure with
      brachytherapy as monotherapy. Complications involve primarily the urinary tract.
      Ideal candidates have a PSA of =10, Gleason score of =7, and low-volume/low-stage
      disease (stage T1c or T2a). Patients with more-advanced disease are candidates
      for brachytherapy combined with external-beam radiation therapy (EBRT). For high
      risk men with multiple adverse prognostic features, consideration should be given
      to clinical trials investigating innovative treatment combinations (eg, the
      addition of androgen blockade, and EBRT). CONCLUSIONS: The rarity of failures
      after 5 years and the absence of recurrence after 10 years suggest a that
      brachytherapy for localized prostate cancer can provide durable disease control.
      Future improvements in pathologic tools may lead to selection of patients more
      likely to respond well to brachytherapy.

PMID- 11326173
TI  - Economic impact of the growing population of breast cancer survivors.

PMID- 11326174
TI  - Focal hepatic enhancement on computed tomography in a patient with non-small cell
      lung carcinoma.

PMID- 11326175
TI  - Infectious complications of cutaneous t-cell lymphoma.

PMID- 11326176
TI  - Cancer: an experiment education.

PMID- 11326177
TI  - Can myocardial infarction be rapidly identified in emergency department patients
      who have left bundle-branch block?
AB  - STUDY OBJECTIVES: Fibrinolytic therapy is recommended for patients who have chest
      pain and left bundle-branch block (LBBB). However, the presence of baseline ECG
      abnormalities makes early accurate identification of acute myocardial infarction
      (AMI) difficult. The predictive ability of clinical and ECG variables for
      identifying patients with LBBB and AMI has not been well studied. We sought to
      determine the prevalence and predictors of myocardial infarction among patients
      presenting to the emergency department with LBBB on the initial ECG who were
      evaluated for myocardial infarction. METHODS: All patients presenting to the ED
      were prospectively risk stratified on the basis of clinical and historical
      variables. ECGs from patients with LBBB were compared retrospectively with
      previously published criteria for identification of AMI. The ability of a new
      LBBB to predict AMI was also determined. RESULTS: Twenty-four (13%) of the 182
      patients with LBBB had AMI. Clinical and historical variables were similar in
      patients with and without AMI. A new LBBB had a sensitivity of 42% and a
      specificity of 65%. The presence of concordant ST-segment elevation or depression
      had specificities and positive predictive values of 100%; however, sensitivities
      were only 8% and 17%, respectively. The best diagnostic criterion was the
      presence of concordant ST-segment elevation or depression on the ECG or an
      initially elevated creatine kinase MB (sensitivity, 63%; specificity, 99%).
      CONCLUSION: ECG criteria for identifying patients with AMI and LBBB identify only
      a small minority of patients with AMI. Treating all patients with LBBB and chest
      pain with fibrinolytics would result in treatment of a significant number of
      patients without AMI.

PMID- 11326178
TI  - Which patients with suspected myocardial ischemia and left bundle-branch block
      should receive thrombolytic agents?

PMID- 11326179
TI  - Intravenous morphine reduces plasma endothelin 1 concentration through activation
      of neutral endopeptidase 24.11 in patients with myocardial infarction.
AB  - STUDY OBJECTIVE: Morphine has multiple cardiovascular effects, but its action on
      hydrolysis of endothelin 1 (ET-1) has not been investigated. METHODS: We measured
      plasma levels of ET-1, C-terminal degradation products of ET-1, and neutral
      endopeptidase 24.11 (NEP) in 68 patients with acute Q-wave myocardial infarction
      and 29 control subjects. All the patients underwent blood sampling at initial
      presentation and 10 minutes later. Thirty-six of those with Q-wave myocardial
      infarction intravenously received 3 mg of morphine immediately after the first
      sampling (group 1), and the other 32 received the same after the second sampling
      (group 2). Twenty-four of the control subjects (group 3) were randomized to the
      protocol of group 1, and the remaining 5 subjects (group 4) were randomized to
      the protocol of group 2. RESULTS: The plasma ET-1 levels were significantly
      higher in groups 1 and 2 than in groups 3 and 4 (control groups). In group 1, the
      ET-1 level decreased significantly at second blood samplings (2.5+/-0.4 pmol/L
      versus 1.7+/-0.6 pmol/L, P <.001), whereas there were no definite changes of ET-1
      levels in group 2 (2.5+/-0.5 pmol/L versus 2.6+/-0.6 pmol/L, P =not significant).
      However, the C-terminal degradation products increased significantly at second
      blood samplings in group 1 (0.8+/-0.2 pmol/L versus 1.3+/-0.4 pmol/L, P <.001),
      whereas there were no definite changes in group 2 (0.9+/-0.3 pmol/L versus 0.9+/
      0.4 pmol/L, P =not significant). There was no significant difference in baseline
      NEP activities between groups 1 and 2 (5.02+/-1.30 nmol/mg protein versus 5.06+/
      1.48 nmol/mg protein, P =not significant). However, the NEP activities at second
      blood samplings declined significantly in group 1 (9.76+/-1.76 nmol/mg protein, P
      <.001 versus baseline), whereas no definite changes were observed in group 2
      (5.09+/-1.62 nmol/mg protein, P =not significant versus baseline). CONCLUSION:
      Intravenous morphine may increase NEP activities to accentuate hydrolysis of ET
      1.

PMID- 11326180
TI  - Overview: diagnosing acute cardiac ischemia in the emergency department. A report
      from the National Heart Attack Alert Program.

PMID- 11326181
TI  - Diagnosing acute cardiac ischemia in the emergency department: a systematic
      review of the accuracy and clinical effect of current technologies.
AB  - STUDY OBJECTIVE: Acute cardiac ischemia (ACI) encompasses the diagnoses of
      unstable angina pectoris and acute myocardial infarction (AMI). Accurate
      diagnosis and triage of patients with ACI in the emergency department should
      increase survival for these patients and reduce unnecessary hospital admissions.
      METHODS: We conducted a systematic review of the English-language literature
      published between 1966 and December 1998 on the accuracy and clinical effect of
      diagnostic technologies for ACI. We evaluated prospective and retrospective
      studies of adult patients who presented to the ED with symptoms suggesting ACI.
      Outcomes were diagnostic performance (test sensitivity and specificity) and
      measures of clinical effect. Meta-analyses were performed when appropriate. A
      decision and cost-effectiveness analysis was conducted that investigated various
      diagnostic strategies used in the diagnosis of ACI in the ED. RESULTS: We
      screened 6,667 abstracts, reviewed 407 full articles, and included 106 articles
      articles in the main analysis. Single measurements of biomarkers at presentation
      to the ED have low sensitivity for AMI, although they have high specificity.
      Serial measurements greatly increase the sensitivity for AMI while maintaining
      their excellent specificity. Diagnostic technologies to evaluate ACI in selected
      populations, such as electrocardiography, sestamibi perfusion imaging, and stress
      ECG, may have very good to excellent sensitivity; however, they have not been
      sufficiently studied. The Goldman Chest Pain Protocol has good sensitivity (about
      90%) for AMI but has not been shown to result in any differences in
      hospitalization rate, length of stay, or estimated costs in the single clinical
      effect study performed. Its applicability to patients with unstable angina
      pectoris has not been evaluated. The use of an Acute Cardiac Ischemia-Time
      Insensitive Predictive Instrument led to the appropriate triage of 97% of
      patients with ACI presenting to the ED and reduced unnecessary hospitalizations.
      CONCLUSION: Many of the current technologies remain underevaluated, especially
      regarding their clinical effect. The extent to which combinations of tests may
      provide better accuracy than any single test needs further study.

PMID- 11326182
TI  - Accuracy and clinical effect of out-of-hospital electrocardiography in the
      diagnosis of acute cardiac ischemia: a meta-analysis.
AB  - STUDY OBJECTIVE: We sought to evaluate quantitatively the evidence on the
      diagnostic performance of out-of-hospital ECG for the diagnosis of acute cardiac
      ischemia (ACI) and acute myocardial infarction (AMI) and the clinical effect of
      out-of-hospital thrombolysis. METHODS: We conducted a systematic review and meta
      analysis of the English-language literature published between 1966 and December
      1998 on the diagnostic accuracy of out-of-hospital ECG and the clinical effect of
      out-of-hospital thrombolysis. Both prospective and retrospective studies
      qualified for the assessment of diagnostic performance. For clinical effect, data
      from prospective nonrandomized studies were synthesized separately from data from
      randomized trials. Diagnostic performance was assessed by using estimates of test
      sensitivity, specificity, and diagnostic odds ratios and was summarized by using
      summary receiver-operating characteristic curves. Measures of clinical effect
      included time savings, early ventricular function, early mortality, and long-term
      survival. RESULTS: Diagnostic accuracy was evaluated in 11 studies with a total
      of 7,508 patients. Data were available for ACI in 5 studies and for AMI in 8
      studies. For ACI, the random-effects pooled sensitivity was 76% (95% CI, 54% to
      89%), the specificity was 88% (95% CI, 67% to 96%), and the diagnostic odds ratio
      was 23 (95% CI, 6.3 to 85). The respective figures for AMI were sensitivity of
      68% (95% CI, 59% to 76%), specificity of 97% (95% CI, 89% to 92%), and diagnostic
      odds ratio of 104 (95% CI, 48 to 224). Both in nonrandomized (n=4, total 1,531
      patients) and randomized (n=9, total 6,643 patients) studies, out-of-hospital
      thrombolysis shortened the time from onset of symptoms to thrombolytic treatment
      by 40 to 60 minutes. Data on short-term ejection fraction were sparse. Hospital
      mortality was reduced by 16% (95% CI, 2% to 27%) among randomized trials, and a
      similar estimate of effect was seen in nonrandomized studies. There was no clear
      effect on long-term mortality, but data were sparse. CONCLUSION: Out-of-hospital
      ECG has excellent diagnostic performance for AMI and very good performance for
      ACI. Out-of-hospital thrombolysis achieves time savings and improves short-term
      mortality, but the effect on long-term mortality is unknown.

PMID- 11326183
TI  - Accuracy of imaging technologies in the diagnosis of acute cardiac ischemia in
      the emergency department: a meta-analysis.
AB  - STUDY OBJECTIVE: We sought to quantitatively evaluate the evidence on the
      diagnostic performance of imaging technologies (including rest and stress
      echocardiography and technetium-99m sestamibi scanning) for the diagnosis of
      acute cardiac ischemia and acute myocardial infarction in the emergency
      department. METHODS: We conducted a systematic review and meta-analysis of the
      English-language literature published between 1966 and December 1998. Both
      prospective and retrospective studies qualified for the assessment of diagnostic
      performance. Diagnostic performance was assessed by means of random-effect
      estimates of test sensitivity, specificity, and the diagnostic odds ratio and was
      summarized by using summary receiver-operating characteristic curves. RESULTS:
      Diagnostic accuracy was evaluated in 10 studies of rest echocardiography, 2
      studies of dobutamine stress echocardiography, and 6 studies of technetium-99m
      sestamibi scanning. However, only 3 rest echocardiography and 5 technetium-99m
      sestamibi studies evaluated patients strictly in the ED setting. Patient
      populations were often highly selected to represent low- or moderate-risk groups.
      When limited to ED studies, rest echocardiography showed excellent sensitivity of
      93% (95% CI, 81% to 97%) and good specificity of 66% (95% CI, 43% to 83%). The
      results were similar when all studies were considered, including data from
      reports of admitted patients and patients sent to the cardiac care unit. There
      was insufficient literature on stress echocardiography in the ED to properly
      assess the technology. Technetium-99m sestamibi scanning also showed excellent
      sensitivity (range, 91.5% to 100%) and good specificity (range, 49.3% to 84.4%)
      for acute myocardial infarction; for acute cardiac ischemia, the random-effects
      pooled sensitivity was 89% (95% CI, 73% to 96%), and the pooled specificity was
      77% (95% CI, 63% to 87%). CONCLUSION: For selected low- and moderate-risk patient
      groups, echocardiography and technetium-99m sestamibi imaging appear to have very
      good diagnostic performance with a similar sensitivity and specificity profile.
      More evidence should be accumulated on their performance specifically in the ED
      setting.

PMID- 11326184
TI  - Accuracy of biomarkers to diagnose acute cardiac ischemia in the emergency
      department: a meta-analysis.
AB  - STUDY OBJECTIVE: We sought to evaluate quantitatively the evidence on the
      diagnostic performance of presentation and serial biochemical markers for
      emergency department diagnosis of acute cardiac ischemia (ACI), including acute
      myocardial infarction (AMI) and unstable angina. METHODS: We conducted a
      systematic review and meta-analysis of the English-language literature published
      between 1966 and December 1998. We examined the diagnostic performance of
      creatine kinase, creatine kinase-MB, myoglobin, and troponin I and T testing.
      Diagnostic performance was assessed by using estimates of test sensitivity and
      specificity and was summarized by summary receiver-operating characteristic
      curves. RESULTS: Only 4 studies were found that evaluated all patients with ACI;
      73 were found that focused only on a diagnosis of AMI. To diagnose ACI,
      presentation biomarker tests had sensitivities of 16% to 19% and specificities of
      96% to 100%; serial biomarker tests had sensitivities of 31% to 45% and
      specificities of 95% to 98%. Considering only the diagnosis of AMI, presentation
      biomarker tests had summary sensitivities of 37% to 49% and summary specificities
      of 87% to 97%; serial biomarker tests had summary sensitivities of 79% to 93% and
      summary specificities of 85% to 96%. Variation of test sensitivity was best
      explained by test timing. Longer symptom duration or time between serial tests
      yielded higher sensitivity. CONCLUSION: The limited evidence available to
      evaluate the diagnostic accuracy of biomarkers for ACI suggests that biomarkers
      have very low sensitivity to diagnose ACI. Thus, biomarkers alone will greatly
      underdiagnose ACI and will be inadequate to make triage decisions. For AMI
      diagnosis alone, multiple testing of individual biomarkers over time
      substantially improves sensitivity, while retaining high specificity, at the
      expense of additional time. Further high-quality studies are needed on the
      clinical effect of using biomarkers for patients with ACI in the ED and on
      optimal timing of serial testing and in combination with other tests.

PMID- 11326185
TI  - The emergency department on-call backup crisis: finding remedies for a serious
      public health problem.

PMID- 11326186
TI  - A room with a view: on-call specialist panels and other health policy challenges
      in the emergency department.

PMID- 11326187
TI  - Pulmonary embolism: making sense of the diagnostic evaluation.
AB  - Despite the publication of the Prospective Investigation of Pulmonary Embolism
      Diagnosis in 1990, the diagnostic evaluation of pulmonary embolism continues to
      be approached in an inconsistent fashion. The reasons for this are unclear but
      likely have to do with inadequate methods for predicting pretest probability of
      disease and the inconvenience and perceived risk of pulmonary angiography.
      Because pulmonary embolism and its treatment carry substantial risk of morbidity
      and mortality, a consistent approach to evaluation is desirable. This article
      reviews large, prospective studies that suggest that it may be unnecessary to
      diagnose pulmonary embolism with the certainty that pulmonary angiography allows.
      Finally, the article proposes an algorithm that may be acceptable to patients and
      clinicians alike if safety is confirmed in future prospective studies.

PMID- 11326188
TI  - Report of the Task Force on Residency Training Information (2000-2001), American
      Board of Emergency Medicine.
AB  - The American Board of Emergency Medicine gathers extensive background information
      on emergency medicine residents and the programs in which they train. We present
      the fourth annual report on the status of US emergency medicine residency
      programs.

PMID- 11326190
TI  - Consequences of delayed diagnosis of Rocky Mountain spotted fever in children-
      West Virginia, Michigan, Tennessee, and Oklahoma, May--July 2000.

PMID- 11326191
TI  - Striking the balance.

PMID- 11326189
TI  - Diver with decompression injury, elevation of serum transaminase levels, and
      rhabdomyolysis.
AB  - A 43-year-old female recreational scuba diver presented to the emergency
      department 1 hour after a rapid, uncontrolled ascent. Her presentation included
      progressing confusion, slow and slurred speech, and complaints of headache and
      hypesthesia over her forearms and anterior thighs bilaterally. Differential
      diagnosis included arterial gas embolism and decompression sickness. She
      underwent recompression therapy with US Navy Table 6 within 120 minutes of her
      ascent. After recompression therapy, the patient had signs and symptoms
      consistent with severe rhabdomyolysis, including creatine kinase levels of 36,000
      U/L and myoglobinuria.

PMID- 11326192
TI  - Last call.

PMID- 11326193
TI  - The waiting room.

PMID- 11326194
TI  - Sensitivity of the simpliRED D-dimer assay.

PMID- 11326195
TI  - Practical application of the prudent layperson standard.

PMID- 11326196
TI  - Practical application of the prudent layperson standard.

PMID- 11326198
TI  - A case of severe withdrawal from gamma-hydroxybutyrate.

PMID- 11326199
TI  - Sufficient dosing of intravenous magnesium for severe asthma.

PMID- 11326211
TI  - What do we know?

PMID- 11326212
TI  - Audio presence intervention for decreasing agitation in people with dementia.
AB  - Researchers have demonstrated the utility of various nonpharmacologic
      interventions in decreasing or preventing agitation in elderly nursing home
      residents with dementia. Auditory intervention strategies are one behavioral
      approach. We tested a modified version of simulated presence therapy called audio
      presence intervention (API). In 28 episodes of agitation among seven residents,
      API produced a significant decline in agitation level as measured by four items
      from the Haycox Rating Scale. However, in six episodes (four residents),
      agitation stayed the same or worsened. The results of this study pose more
      questions than answers and should stimulate nurse researchers to further
      investigate auditory intervention for control of agitation elders with dementia.

PMID- 11326213
TI  - Recognizing pain in the institutionalized elder with dementia.
AB  - Of the approximately 2 million elders residing in nursing homes, experts estimate
      that 49% to 83% are experiencing pain. Elders in nursing homes have a high
      incidence of cognitive impairment, possibly as high as 50%. The verbalization of
      pain can be difficult for those with cognitive impairment, and elders with
      dementia may be undertreated and unknowingly allowed to suffer. This article
      summarizes what is known about pain assessment in the cognitively impaired
      elderly who reside in nursing homes. Clinical practice implications were derived
      from this summary. Until accurate ways of assessing pain are discovered, nurses
      must be educated to the prevalence of pain in cognitively impaired elders and the
      subtle ways in which it might be detected. Nursing practice is about eliminating
      suffering. Relieving suffering in those most vulnerable and unable to express
      their needs is critical.

PMID- 11326214
TI  - A pilot study of the relationship between discomfort and agitation in patients
      with dementia.
AB  - People with dementia often have painful conditions that go unnoticed because of
      their communication problems. Signs of pain in this population may include
      agitation and observable behaviors associated with discomfort. Agitation,
      discomfort, and severity of dementia were evaluated in 33 Veterans Affairs
      nursing home patients using the Cohen-Mansfield Agitation Inventory, the
      Discomfort Scale, and the Global Deterioration Scale, respectively. Findings
      revealed statistically significant positive relationships between agitation and
      severity of dementia (r = 0.34, P = 0.01), discomfort and severity of dementia (r
      = 0.44, P = 0.01), and agitation and discomfort (r = 0.50, P = 0.003). In a
      multiple regression analysis, agitation was significantly associated with
      discomfort (R(2) =.14, P = 0.02) after controlling for dementia severity. These
      preliminary findings suggest that discomfort may be a source of agitation.

PMID- 11326215
TI  - A glider swing intervention for people with dementia.
AB  - The soothing, repetitive movement of rocking and swinging is well known to anyone
      who has enjoyed a porch swing or rocking chair. Positive effects of rocking have
      been reported. However, investigations on its effect in people with dementia are
      limited. The purposes of this quasi-experimental, repeated-measures design study
      were to measure the effects of a glider swing on emotions, relaxation, and
      aggressive behaviors in a group of nursing home residents with dementia (n = 30).
      Data were obtained during a 5-day baseline phase, a 10-day intervention phase,
      and a 5-day posttreatment phase. Subjects were placed on the glider for 20
      minutes each day during the intervention phase. The results of the study indicate
      that the glider intervention significantly improved emotions and relaxation. The
      most noted changes were found after 10 minutes of swinging. However, no
      differences were found in aggressive behaviors.

PMID- 11326216
TI  - An evaluation of two bathing products in a chronic care setting.

PMID- 11326217
TI  - Kathleen Coen Buckwalter, PhD, RN, FAAN.

PMID- 11326218
TI  - Macular degeneration in older adults.
AB  - Macular degeneration, a chronic, progressive eye disease, is the leading cause of
      blindness in older Americans. As the aging segment of society grows, the number
      of seniors diagnosed with macular degeneration will increase. Caring for
      individuals with this disease is a task that will be increasingly allotted to
      nurses. This article presents information on the disease process, risk factors,
      medical therapies, and nursing implications involved in caring for individuals
      with this condition. When nurses gain a thorough understanding of macular
      degeneration and the implications of living with this disease, quality care can
      be provided to an expanding segment of society.

PMID- 11326219
TI  - Possible consequences of social drinking in the early stages of Alzheimer
      disease.
AB  - Although research supports the idea that alcohol is not a risk factor for
      developing Alzheimer disease (AD), surprisingly little attention has been given
      to the role of social drinking in the early stages of the disorder. The current
      review highlights potential alcohol- and disease-related interactions on
      neurologic, cognitive, and behavioral functioning in individuals experiencing the
      early stages of AD. Understanding how alcohol interacts with AD can benefit both
      treatment providers (eg, interpreting clinical tests) and caregivers (eg,
      managing disruptive behaviors) by providing important clues to potentially
      reversible impairments that may negatively affect the everyday functioning of
      individuals with the disorder.

PMID- 11326220
TI  - Communication from individuals with advanced DAT: can it provide clues to their
      sense of self-awareness and well-being?
AB  - Often communication from people with advanced dementia of the Alzheimer type
      (DAT) is regarded as incoherent and meaningless. However, with careful listening
      and observation, such communication often becomes more understandable. To better
      understand DAT communication, the investigators designed an exploratory
      qualitative study to videotape and critically analyze conversations between a
      clinical nurse specialist and 15 subjects with DAT ranging from mild to severe.
      One of the findings was that, even in later stages, indications were given that
      subjects had self-awareness of their cognitive decline. The investigators further
      examined the communication of the five most cognitively impaired subjects for
      other indications of self-awareness and well-being. To demonstrate this premise
      of awareness of cognitive decline and self in the later stages of DAT, excerpts
      from communication received from five subjects with advanced cognitive impairment
      are presented.

PMID- 11326222
TI  - Publications of The American Association for Thoracic Surgery, or "How to be all
      things to...".

PMID- 11326221
TI  - Hormones as antiaging remedies.

PMID- 11326223
TI  - Enter the era of facilitated anastomotic devices for coronary bypass surgery.

PMID- 11326224
TI  - Cell transplantation comes of age.

PMID- 11326225
TI  - A bypass for the Institutional Review Board: reflections on the Cleveland Clinic
      study of the Batista operation.

PMID- 11326227
TI  - Computer-enhanced "robotic" cardiac surgery: experience in 148 patients.
AB  - OBJECTIVE: A computer-enhanced instrumentation system was used in 148 patients to
      minimize access in cardiac surgical procedures. METHODS: The da Vinci
      telemanipulation system (Intuitive Surgical, Mountain View, Calif) provides a
      high-resolution 3-dimensional videoscopic image and allows remote, tremor-free,
      and scaled control of endoscopic surgical instruments with 6 degrees of freedom.
      By April 2000, the system had been used in 131 patients for coronary artery
      bypass grafting and 17 patients for mitral valve repair. In the coronary bypass
      group, the system was used in one of three ways: (1) to take down the internal
      thoracic artery followed by a minimally invasive direct coronary bypass procedure
      (n = 81); (2) to perform the anastomosis between the internal thoracic artery and
      the left anterior descending coronary artery in standard-sternotomy coronary
      bypass (n = 15); or (3) for total endoscopic coronary artery bypass grafting to
      anastomose the left internal thoracic artery to the left anterior descending on
      the arrested heart (n = 27) or the beating heart (n = 8). In 17 patients with
      nonischemic mitral valve insufficiency the mitral valve was repaired. Closed
      chest cardiopulmonary bypass with cardioplegic arrest (Port-Access technique;
      Heartport, Inc, Redwood City, Calif) was used for arrested-heart total endoscopic
      coronary bypass and mitral valve repair. RESULTS: The da Vinci system allows for
      precise tissue handling and enables the endoscopic performance of cardiac
      surgical tasks that require a high degree of dexterity (coronary anastomosis,
      mitral valve repair). No technical mishaps have occurred. The internal thoracic
      artery was successfully taken down in 79 of 81 patients in the group undergoing
      minimally invasive coronary bypass and, after a steep learning curve, is
      currently performed in less than 40 minutes. The postoperative patency rate is
      96.3%. Total endoscopic coronary bypass was completed in 22 of 27 cases with
      95.4% patency as demonstrated by angiography at 3 months' follow-up. Closed-chest
      endoscopic beating-heart bypass grafting was successfully performed in 2 out of 8
      patients with the use of a new endoscopic stabilizer. In the group having mitral
      valve repair, primary endoscopic computer-enhanced repair was successfully
      completed in 14 of 17 patients; three others had to be changed to a standard
      endoscopic technique, including 1 who required valve replacement. At 3 months'
      follow-up, 1 additional patient underwent early reoperation for recurrent mitral
      insufficiency. Overall early and late mortality in this cohort of 148 patients
      was 2.0% and was not related to the use of the system. CONCLUSION: In conclusion,
      computer-enhanced endoscopic cardiac surgery can be performed safely in selected
      patients. Internal thoracic artery takedown is now routinely performed with good
      results. Total endoscopic coronary bypass is feasible on the arrested heart but
      does not offer a major benefit over the minimally invasive direct approach
      because cardiopulmonary bypass is still required. The early clinical experience
      with closed-chest beating-heart bypass grafting outlines the limitations of this
      approach despite some procedural success.

PMID- 11326228
TI  - Early clinical experience with a new sutureless anastomotic device for proximal
      anastomosis of the saphenous vein to the aorta.
AB  - BACKGROUND: Avoiding aortic side clamping is useful to avoid local particulate
      embolization. A device that allows a saphenous vein graft to be anastomosed to
      the aorta without aortic manipulation is clinically evaluated. METHODS AND
      RESULTS: From July 1999 to March 2000, 17 patients who underwent myocardial
      revascularization had an aorta-saphenous vein graft anastomosis performed by
      means of an aortic anastomotic device. Eight were operated on with
      cardiopulmonary bypass and 9 without. The proximal anastomoses created by the
      aortic anastomotic device were performed before the institution of
      cardiopulmonary bypass or before the related distal anastomosis was performed. In
      11 patients transcranial Doppler ultrasound was used. In 1 (6%) patient the
      saphenous vein graft was not deployed, and in 2 (12%) a single suture was added
      for minor bleeding. None of the 11 patients evaluated with transcranial Doppler
      ultrasound had evidence of particulate embolization during the procedure. No
      patient died or was reoperated on for bleeding. Six (35%) patients had a
      postoperative angiogram 48 +/- 26 days after the operation that showed widely
      patent proximal anastomoses. CONCLUSIONS: Use of an aortic anastomotic device
      allows a sutureless anastomosis to be created between the aorta and saphenous
      vein graft. The device could be used in totally endoscopic myocardial
      revascularization. A second-generation device is ready to solve the problems
      encountered and to increase the ease in handling the device.

PMID- 11326229
TI  - Facilitated coronary anastomosis using a nitinol U-Clip device: bovine model.
AB  - OBJECTIVE: The coronary anastomosis is the most difficult part of the coronary
      bypass procedure, particularly when using a minimally invasive technique. Methods
      to facilitate coronary anastomosis will make the minimally invasive approach to
      coronary bypass feasible. We sought preclinical validation and testing of the
      design and efficacy of a self-closing penetrating clip that can be used to
      facilitate the creation of graft-to-coronary end-to-side anastomosis. METHODS:
      The nitinol U-Clip device (Coalescent Surgical, Inc, Sunnyvale, Calif) was used
      in 13 consecutive calves (63-118 kg). In each animal, the device was (1) used to
      create an anastomosis of the right internal thoracic artery to a coronary artery
      with the heart beating and (2) compared to polypropylene suture when used to
      repair two carotid arteriotomies. Intraoperative, 1-week, 8-week, and 26-week
      postoperative angiograms and detailed histopathologic examinations were used to
      evaluate anastomotic patency and healing characteristics. RESULTS: The nitinol U
      Clip device successfully created right internal thoracic artery-coronary artery
      anastomoses and repaired carotid arteriotomy sites in 13 consecutive calves. The
      clip was precisely placed by means of the integrated suture and needle in a
      fashion similar to that used for conventional suture. The clip met design
      specifications by reliable release and automatic closure, thereby eliminating
      knot tying and assisted suture management. At the time of harvest, angiography
      showed widely patent coronary anastomoses (FitzGibbon grade A criteria, n = 13)
      and carotid arteriotomy repair sites (n = 13). Histopathologic evaluation
      confirmed normal healing with smooth circumferential neointimal resurfacing at
      the anastomotic and repair sites. CONCLUSIONS: The nitinol U-Clip design and
      function was validated in the formation of bovine coronary anastomoses on the
      beating bovine heart with excellent graft patency and healing characteristics.
      The nitinol U-Clip device tests favorably when compared with conventional sutures
      in carotid artery repair.

PMID- 11326230
TI  - Cellular therapy reverses myocardial dysfunction.
AB  - OBJECTIVES: Cellular cardiomyoplasty refers to the implantation of autologous
      skeletal muscle cells into the myocardium to reinforce its structure and
      function. In this study a reproducible method for the creation of a myocardial
      lesion was developed. The functional benefit of cell implantation was evaluated
      by 2-dimensional echocardiography for global contraction and color kinesis
      echocardiography, which allows the precise assessment of the regional
      contraction. METHODS: A left ventricular intramyocardial injection with snake
      cardiotoxin was carried out on a sheep model to induce a well-delineated
      transmural lesion. Three weeks later, the lesion was assessed by
      echocardiography. Thereafter, autologous skeletal muscle cells or culture media
      (control) were injected into the lesion. Two months after cell implantation, the
      myocardial contraction was again evaluated by echocardiography and the implanted
      cells were analyzed by a fast myosin heavy chain antibody. RESULTS: 1. The snake
      cardiotoxin produced a well-delineated transmural lesion in all animals. 2.
      Echocardiographic studies showed a significant improvement in global and regional
      left ventricular function in cell-treated sheep. 3. Histologic analyses
      demonstrated satellite cell survival at the periphery of the lesions. CONCLUSION:
      Satellite cells implanted in a cardiotoxin-induced myocardial lesion survived for
      a 2-month period and were associated with a significant functional improvement of
      both local and global contraction.

PMID- 11326231
TI  - Partial left ventriculectomy for dilated cardiomyopathy: is this an alternative
      to transplantation?
AB  - OBJECTIVE: To determine the late effectiveness of partial left ventriculectomy
      and risk factors for failure. METHODS: Between May 1996 and December 1998,
      partial left ventriculectomy and concomitant mitral valve surgery were performed
      in 62 patients (95% transplant candidates) with a mean age of 54 years (range 17
      72 years). All patients were in New York Heart Association functional class III
      (38%) or IV (62%) because of idiopathic dilated cardiomyopathy (59 patients) or
      ischemic, valvular, or familial cardiomyopathy (1 patient each). Outcomes
      considered for multivariable analysis included implantation of left ventricular
      assist device, return to class IV heart failure, relisting for transplantation,
      and death. RESULTS: Partial left ventriculectomy reduced the left ventricular end
      diastolic diameter immediately preoperatively to immediately postoperatively
      (from 8.4 +/- 1.1 cm to 5.92 +/- 0.8 cm; P =.01), reduced the left ventricular
      end-diastolic volume index (from 133 +/- 48.6 mL to 64.1 +/- 26 mL; P <.0001),
      and increased the left ventricular ejection fraction (from 16 +/- 7.6 to 31.5 +/-
      10.9; P <.0001). Survival was 80% and 60% at 1 and 3 years after surgery and
      freedom from failure was 49% and 26%, respectively. Increased systolic pulmonary
      artery pressure, decreased maximum exercise oxygen consumption, and increased
      left atrial pressure were associated with failure and/or death. The degree of
      preoperative mitral regurgitation did not correlate with clinical outcome.
      CONCLUSIONS: Early and late failures preclude the widespread use of partial left
      ventriculectomy. However, in view of its sometimes beneficial effect, use in
      situations that do not allow for transplantation or as a biologic bridge to
      transplantation may be appropriate.

PMID- 11326232
TI  - Prediction of coronary artery disease in patients undergoing operations for
      mitral valve degeneration.
AB  - OBJECTIVES: We sought to develop and validate a model that estimates the risk of
      obstructive coronary artery disease in patients undergoing operations for mitral
      valve degeneration and to demonstrate its potential clinical utility. METHODS: A
      total of 722 patients (67% men; age, 61 +/- 12 years) without a history of
      myocardial infarction, ischemic electrocardiographic changes, or angina who
      underwent routine coronary angiography before mitral valve prolapse operations
      between 1989 and 1996 were analyzed. A bootstrap-validated logistic regression
      model on the basis of clinical risk factors was developed to identify low-risk (<
      or =5%) patients. Obstructive coronary atherosclerosis was defined as 50% or more
      luminal narrowing in one or more major epicardial vessels, as determined by means
      of coronary angiography. RESULTS: One hundred thirty-nine (19%) patients had
      obstructive coronary atherosclerosis. Independent predictors of coronary artery
      disease include age, male sex, hypertension, diabetes mellitus,and
      hyperlipidemia. Two hundred twenty patients were designated as low risk according
      to the logistic model. Of these patients, only 3 (1.3%) had single-vessel
      disease, and none had multivessel disease. The model showed good discrimination,
      with an area under the receiver-operating characteristic curve of 0.84. Cost
      analysis indicated that application of this model could safely eliminate 30% of
      coronary angiograms, corresponding to cost savings of $430,000 per 1000 patients
      without missing any case of high-risk coronary artery disease. CONCLUSION: A
      model with standard clinical predictors can reliably estimate the prevalence of
      obstructive coronary atherosclerosis in patients undergoing mitral valve prolapse
      operations. This model can identify low-risk patients in whom routine
      preoperative angiography may be safely avoided.

PMID- 11326233
TI  - Time course of reverse remodeling of the left ventricle during support with a
      left ventricular assist device.
AB  - BACKGROUND: Support with a left ventricular assist device leads to normalization
      of left ventricular chamber geometry, regression of myocyte hypertrophy,
      alterations in left ventricular collagen content, and normalized expression of
      genes involved with excitation-contraction coupling in patients with heart
      failure. The objective of this study was to investigate the time course of these
      processes. METHODS: Passive left ventricular pressure-volume relationships were
      obtained from explanted hearts of 19 patients with heart failure undergoing
      transplantation without left ventricular assist device support, 25 patients with
      heart failure supported before transplantation (duration of support ranging
      between 8 and 155 days), and 5 normal human hearts not suitable for
      transplantation. Left ventricular size was indexed by the volume at which left
      ventricular pressure reached 30 mm Hg. Left ventricular tissue samples were
      probed for sarcoplasmic endoreticular calcium adenosine triphosphatase 2a
      expression and processed for analysis of myocyte diameter and relative myocardial
      collagen content. RESULTS: The volume at which left ventricular pressure reached
      30 mm Hg was not significantly different between hearts without and with assist
      device support for less than 40 days. However, the volume at which left
      ventricular pressure reached 30 mm Hg in patients with assist devices supported
      for more than 40 days was significantly smaller than that of the hearts without
      assist devices but was larger than that of normal hearts. A similar pattern was
      observed for myocyte diameter. Sarcoplasmic endoreticular calcium adenosine
      triphosphatase 2a expression increased to normal levels by about 20 days of
      support with an assist device. Relative collagen content was significantly
      increased in hearts supported for more than 40 days. CONCLUSION: Maximum
      structural reverse remodeling by left ventricular assist devices is complete by
      about 40 days. Molecular reverse remodeling of sarcoplasmic endoreticular calcium
      adenosine triphosphatase 2a expression is quicker, being complete by about 20
      days.

PMID- 11326234
TI  - Sociodemographic and clinical factors associated with low quality of life one
      year after coronary bypass operations: the Israeli coronary artery bypass study
      (ISCAB).
AB  - OBJECTIVES: We sought to examine the effect of sociodemographic characteristics
      and perioperative clinical factors 1 year after coronary bypass operations on low
      health-related quality of life. We also sought to assess the usefulness of an
      additional single question on overall health for identifying patients with low
      health-related quality of life. METHODS: This report is part of the Israeli
      coronary artery bypass study of 1994, in which every patient undergoing isolated
      coronary bypass grafting in Israel was included. The target population for this
      report comprised all survivors beyond 1 year who were 45 to 65 years of age.
      Patients were interviewed before the operations. Self-administered questionnaires
      regarding health-related quality of life (SF-36) were sent to 1724 patients who
      were successfully located 1 year postoperatively, and 1270 questionnaires were
      completed. Low health-related quality of life was defined as the lowest tertile
      of the distribution of scores for the 2 summary components of the SF-36 and the
      single question on overall health. Logistic models were constructed for each of
      the 3 outcomes. RESULTS: Female sex and low socioeconomic background were
      associated with low health-related quality of life in the logistic models. Other
      significant factors were symptoms of angina, sleep disturbances, hypertension,
      high severity of illness scores, hospital readmission, no rehabilitation, and
      hospitals with high perioperative mortality. Of the 3 study outcomes, the model
      for the single question on overall health was the most discriminating (C
      statistic = 0.76 vs 0.70 and 0.70, respectively). CONCLUSIONS: The study
      identifies patients who would most benefit from posthospitalization community
      support after bypass operations. Under circumstances of limited resources, these
      disadvantaged groups should be targeted as a priority. Encouraging participation
      in existing rehabilitation programs or introducing telephone hotlines could
      improve health-related quality of life after coronary bypass grafting without
      large investments.

PMID- 11326235
TI  - Thrombotic complications in beating heart operations.
AB  - BACKGROUND: Off-pump coronary artery operations have recently gained popularity
      among the community of cardiac surgeons. Because the use of cardiopulmonary
      bypass is avoided, full anticoagulation is generally not sought to decrease
      perioperative blood loss and transfusion needs. Traditionally, patients
      undergoing coronary artery bypass operations with cardiopulmonary bypass are not
      considered at risk of having venous or arterial thromboembolic complications, and
      prophylaxis is generally not recommended. METHODS AND RESULTS: We have reviewed
      our experience with off-pump coronary bypass operations, focusing on
      thromboembolic complications with clinical manifestations, and compared these
      findings with our experience with cardiopulmonary bypass operations. In our
      series of 500 off-pump cases, thromboembolic complications occurred in 1%,
      causing death in 1 patient, whereas in a contemporary cohort of 1476 patients
      operated on with cardiopulmonary bypass, thromboembolic complications resulted in
      stroke in 0.5% of the cases. This difference did not reach statistical
      significance. CONCLUSIONS: Thromboembolic complications in off-pump coronary
      bypass operations are comparable with those in cardiopulmonary bypass operations.
      Although the prevalence of this complication remains low, the associated
      morbidity should lead to reconsideration of prophylactic measures.

PMID- 11326236
TI  - Cerebral effects of cold reperfusion after hypothermic circulatory arrest.
AB  - OBJECTIVES: This study was undertaken to explore whether an interval of cold
      reperfusion can improve cerebral outcome after prolonged hypothermic circulatory
      arrest. METHODS: Sixteen pigs (27-30 kg) underwent 90 minutes of circulatory
      arrest at a brain temperature of 20 degrees C. Eight animals were rewarmed
      immediately after hypothermic circulatory arrest (controls), and 8 were
      reperfused for 20 minutes at 20 degrees C and then rewarmed (cold reperfusion).
      Electrophysiologic recordings, fluorescent microsphere determinations of cerebral
      blood flow, calculations of cerebral oxygen consumption, and direct measurements
      of intracranial pressure (millimeters of mercury) were obtained at baseline (37
      degrees C), before hypothermic circulatory arrest, after discontinuing
      circulatory arrest at 37 degrees C deep brain temperature, and at 2, 4, and 6
      hours thereafter. Histopathologic features and percent brain water were
      determined after the animals were sacrificed. RESULTS: Cerebral blood flow and
      oxygen consumption decreased during cooling: cerebral oxygen consumption returned
      to baseline levels after 4 hours, but cerebral blood flow remained depressed
      until 6 hours in both groups. Cold reperfusion failed to improve
      electrophysiologic recovery or to reduce brain weight, but median intracranial
      pressure increased significantly less after cold reperfusion than in controls (P
      =.02). Although no significant difference in the incidence of histopathologic
      abnormalities between groups was found, all 3 animals with an intracranial
      pressure of more than 15 mm Hg after immediate rewarming had histopathologic
      lesions, and high intracranial pressure was more prevalent among all animals with
      subsequent histopathologic lesions (P =.03). CONCLUSIONS: Cold reperfusion
      significantly inhibited the rise in intracranial pressure seen in control pigs
      after 90 minutes of circulatory arrest at 20 degrees C, suggesting that cold
      reperfusion may decrease cerebral edema and thereby improve outcome after
      prolonged hypothermic circulatory arrest.

PMID- 11326237
TI  - The fate of a tissue-engineered cardiac graft in the right ventricular outflow
      tract of the rat.
AB  - OBJECTIVE: The synthetic materials currently available for the repair of cardiac
      defects are nonviable, do not grow as the child develops, and do not contract
      synchronously with the heart. We developed a beating patch by seeding fetal
      cardiomyocytes in a biodegradable scaffold in vitro. The seeded patches survived
      in the right ventricular outflow tract of adult rats. METHODS: Cultured fetal or
      adult rat heart cells (1 x 10(6) cells) were seeded into a gelatin sponge (15 x
      15 x 1 mm), and the cell number was expanded in culture for 1 or 3 weeks,
      respectively. The free wall of the right ventricular outflow tract in syngeneic
      adult rats was resected and repaired with either unseeded patches or patches
      seeded with either fetal or adult cardiomyocytes (n = 10 for each group). The
      patches were examined histologically over a 12-week period. RESULTS: A
      significant inflammatory reaction was noted in the patch at 4 weeks as the
      scaffold dissolved. At 12 weeks, the gelatin scaffold had completely dissolved.
      Both types of the seeded cells were detected in the patch with 5-bromo-2'
      deoxyuridine staining, and they maintained their continuity. Unseeded patches had
      an ingrowth of fibrous tissue. The patches became thinner between the fourth and
      the twelfth weeks in unseeded (P =.003), fetal (P =.0001), and adult (P =.07)
      cardiomyocyte groups as the scaffold dissolved. The control patch, but not the
      cell-seeded patches, was thinner than the normal right ventricular outflow tract.
      The endocardial surface area of each patch was covered with endothelial cells
      identified by factor VIII staining. CONCLUSIONS: A gelatin patch was used to
      replace the right ventricular outflow tract in syngeneic rats. The seeded cells
      survived in the right ventricular outflow tract after the scaffold dissolved 12
      weeks after implantation. In addition, the unseeded patches encouraged the
      ingrowth of fibrous tissue as the scaffold dissolved and the patches remained
      completely endothelialized.

PMID- 11326238
TI  - Early discharge after coronary artery bypass graft surgery: are patients really
      going home earlier?
AB  - OBJECTIVE: This study was undertaken to determine whether early discharge after
      coronary artery bypass grafting allows patients to return home earlier or merely
      increases the use of outpatient nursing and inpatient rehabilitation services.
      METHODS: Patterns of discharge were analyzed in 407 patients undergoing bypass
      grafting in 1990, when there were no early extubations or fast track protocols,
      and compared with 379 patients in 1998, when these protocols were used. RESULTS:
      Patients in 1998 had a higher prevalence of class IV angina (35.3% vs 22.8%; P
      =.006), urgent/emergency surgery (58.3% vs 44.9%; P =.015), and lower ejection
      fractions (48.9% +/- 16.4% vs 52.9% +/- 13.5%; P =.0002). Despite these increased
      risk factors, 1998 patients spent less time receiving ventilatory support (10.2
      +/- 9.2 vs 26.7 +/- 15.7 hours; P <.001) and had a shorter length of stay (5.4 +/
      2.5 vs 9.2 +/- 4.3 days; P <.001). However, fewer 1998 patients were discharged
      home (56.7% vs 97.0%; P <.0001). A higher percentage of 1998 patients (43.3% vs
      2.9%; P <.00001) were discharged to extended care facilities where their average
      length of stay was 10.6 +/- 15.1 days. Readmission to the Boston Medical Center
      was also more common in 1998 patients (5.3% vs 0.5%; P <.0001). CONCLUSIONS:
      Early extubation and fast track protocols have resulted in earlier discharge from
      acute care facilities. However, the anticipated earlier return to home has been
      offset by the increased use of outpatient nursing services, discharges to
      extended care facilities, and hospital readmissions.

PMID- 11326239
TI  - Radial artery harvesting for coronary bypass operations: neurologic complications
      and their potential mechanisms.
AB  - OBJECTIVES: We sought to determine the incidence of self-reported neurologic hand
      complications after radial artery harvest for coronary artery bypass grafting.
      METHODS: Between February 20, 1996, and December 31, 1999, 615 patients underwent
      coronary bypass operations with radial arteries. A scripted telephone interview
      was performed, collecting data on perceived thumb weakness and sensation
      abnormalities in the distribution of the radial nerve in 560 patients. The
      average time to follow-up interview was 14.5 +/- 9 months. RESULTS: Neurologic
      complications were reported in 30.1%, decreased thumb strength in 5.5%, and any
      sensation abnormality in 18.1% of patients. There was a high rate of symptom
      improvement over an average of 8.7 +/- 7.5 months, such that only 12.1% of
      patients reported symptoms without any improvement. Associations between thumb
      weakness and sensory abnormalities imply median nerve damage in some patients.
      There were statistically significant associations between neurologic
      complications and diabetes, peripheral vascular disease, elevated creatinine
      levels, smoking, and number and site of radial artery harvest. CONCLUSIONS: The
      overall rate of self-reported neurologic complications after radial artery
      harvest was higher than previously reported. These symptoms may be attributable
      to radial and median nerve injury caused by trauma and devascularization. These
      data have important implications not only in attempting to improve harvesting
      techniques but also in guiding informed consent before coronary artery bypass
      grafting.

PMID- 11326240
TI  - The N-methyl-D-aspartate antagonist memantine has no neuroprotective effect
      during hypothermic circulatory arrest: a study in the chronic porcine model.
AB  - BACKGROUND: Glutamate excitotoxicity has an important role in the development of
      brain injury after prolonged hypothermic circulatory arrest. The goal of the
      present study was to determine the potential efficacy of memantine, an N -methyl
      D -aspartate receptor antagonist, to mitigate cerebral injury after hypothermic
      circulatory arrest. METHODS: Twenty pigs (23-33 kg) were randomly assigned to
      receive memantine (5 mg/kg) or placebo in a blinded fashion before a 75-minute
      period of hypothermic circulatory arrest at 20 degrees C. Hemodynamic,
      electroencephalographic, and metabolic monitoring were carried out. The
      intracerebral concentrations of glucose, lactate, glutamate, and glycerol were
      measured by means of enzymatic methods on a microdialysis analyzer. Daily
      behavioral assessment was performed until the animals died or were put to death
      on day 7. Histologic analysis of the brain was carried out in all animals.
      RESULTS: In the memantine group, 5 of 10 animals survived 7 days compared with 9
      of 10 in the placebo group. The median behavioral score at day 7 was 3.5 in the
      memantine group and 7.5 in the placebo group (P >.2). Among the surviving
      animals, medians were 9.0 and 8.0 on day 7 (P >.2), respectively. The medians of
      recovered electroencephalographic bursts were equal in both groups. The median of
      total histopathologic score was 16 in the memantine group and 14 in the placebo
      group (P >.2). There was a negative correlation between glutamate levels and
      electroencephalographic burst recovery (tau = -0.377, P =.043). A positive
      correlation was found between the highest individual glutamate value and
      histopathologic score (tau = 0.336, P =.045). CONCLUSIONS: The present study
      demonstrates that memantine has no neuroprotective effect after hypothermic
      circulatory arrest in the pig. In addition, we have shown the accuracy of
      cerebral glutamate measurements to predict histopathologic injury after
      hypothermic ischemia.

PMID- 11326242
TI  - L-arginine polymers inhibit the development of vein graft neointimal hyperplasia.
AB  - OBJECTIVE: We sought to determine whether L -arginine polymer treatment of vein
      grafts enhances vascular production of nitric oxide and inhibits the development
      of neointimal hyperplasia. METHODS: External jugular veins of New Zealand White
      rabbits (n = 42) were harvested; treated intraluminally for 15 minutes with
      phosphate-buffered saline solution or L -arginine polymer 5, 7, or 9 at either 10
      or 100 micromol/L; and then grafted into the contralateral carotid artery.
      Rabbits were killed after 28 days, and 5-microm sections of vessels were stained
      with hematoxylin and scored for intima/media ratio by using computerized
      morphometric analysis. Separate veins were treated in a similar fashion with
      biotinylated polymers and phosphate-buffered saline solution to assess for
      translocation efficiencies. Finally, vein segments pretreated with either
      phosphate-buffered saline solution or L -arginine polymers were cultured in
      Dulbecco's modified Eagle's medium containing lipopolysaccharide (100 microg/mL)
      and interferon gamma (200 U/mL) for 48 hours before measuring nitric oxide levels
      by means of the Griess reaction. RESULTS: Biotinylated L -arginine polymers
      demonstrated a dose- and length-dependent uptake into intimal and medial cells of
      treated vessels. Nitric oxide levels were significantly higher in vein segments
      treated with 100 micromol/L of L -arginine polymer 9 compared with control
      segments. Finally, the intima/media ratio also reflected both length- and
      concentration-dependent inhibition of neointimal hyperplasia.intima/media ratio
      PBS R5 R7 R9 10 micromol/L 0.909 +/- 0.072 0.920 +/- 0.073 0.861 +/- 0.138 0.710
      +/- 0.122 100 micromol/L 0.924 +/- 0.061 0.581 +/- 0.089* 0.529 +/- 0.093* PBS,
      Phosphate-buffered saline solution; R, L -arginine polymer. *P <.001 versus
      phosphate-buffered saline solution and L -arginine polymer 5 controls (Bonferroni
      corrected value). CONCLUSIONS: Arginine polymers of sufficient length and
      concentration were effective in increasing nitric oxide levels and reducing
      neointimal hyperplasia in this vein graft model.

PMID- 11326243
TI  - Aerosolized prostacyclin (epoprostenol) as an alternative to inhaled nitric oxide
      for patients with reperfusion injury after lung transplantation.

PMID- 11326244
TI  - Aspirin resistance after coronary artery bypass grafting.

PMID- 11326245
TI  - Renal autotransplantation in a patient with acute renal infarction after surgery
      for a dissecting aneurysm.

PMID- 11326246
TI  - Single-stage transpericardial repair of acute aortic dissection associated with
      recoarctation.

PMID- 11326247
TI  - Acute aortic dissection with critical stenoses of the true lumen treated by
      transluminal stent-graft placement and findings one year after treatment.

PMID- 11326248
TI  - Stent-graft implantation through partial sternotomy.

PMID- 11326249
TI  - Mitral valve replacement with mechanical valves in children under two years of
      age.

PMID- 11326250
TI  - Surgical correction of aortic arch hypoplasia associated with crestlike
      protrusion of the superior arch wall and isthmic coarctation.

PMID- 11326251
TI  - The implications of extensive cerebral vascular dysplasia in surgical repair of
      coarctation of the aorta and ventricular septal defect.

PMID- 11326252
TI  - Reversible dilated cardiomyopathy after lobectomy for pulmonary sequestration.

PMID- 11326253
TI  - Distal esophageal perforation caused by tuberculosis.

PMID- 11326254
TI  - Lambert-Eaton myasthenic syndrome associated with an anterior mediastinal small
      cell carcinoma.

PMID- 11326255
TI  - Rupture and dissection in pulmonary artery aneurysms: incidence, cause, and
      treatment--review and case report.

PMID- 11326256
TI  - Right atrial hydatid cyst associated with multiple organ involvement: case
      report.

PMID- 11326257
TI  - Carney's triad paragangliomas.

PMID- 11326258
TI  - Salvage of right gastroepiploic artery graft before pancreatoduodenectomy.

PMID- 11326259
TI  - Community watch.

PMID- 11326260
TI  - LEF1 turns over a new leaf.

PMID- 11326261
TI  - Knocking the SOCS off a tumor suppressor.

PMID- 11326262
TI  - Lessons from a small genome.

PMID- 11326263
TI  - A virus finds its natural killer.

PMID- 11326264
TI  - Linking microarray data to the literature.

PMID- 11326265
TI  - Packaging paternal chromosomes with protamine.

PMID- 11326268
TI  - Verification and initial annotation of the NIA mouse 15K cDNA clone set.

PMID- 11326269
TI  - A novel maternally expressed gene, ATP10C, encodes a putative aminophospholipid
      translocase associated with Angelman syndrome.
AB  - Lack of a maternal contribution to the genome at the imprinted domain on proximal
      chromosome 15 causes Angelman syndrome (AS) associated with neurobehavioral
      anomalies that include severe mental retardation, ataxia and epilepsy. Although
      AS patients have infrequent mutations in the gene encoding an E6-AP ubiquitin
      ligase required for long-term synaptic potentiation (LTP), most cases are
      attributed to de novo maternal deletions of 15q11-q13. We report here that a
      novel maternally expressed gene, ATP10C, maps within the most common interval of
      deletion and that ATP10C expression is virtually absent from AS patients with
      imprinting mutations, as well as from patients with maternal deletions of 15q11
      q13.

PMID- 11326270
TI  - A literature network of human genes for high-throughput analysis of gene
      expression.
AB  - We have carried out automated extraction of explicit and implicit biomedical
      knowledge from publicly available gene and text databases to create a gene-to
      gene co-citation network for 13,712 named human genes by automated analysis of
      titles and abstracts in over 10 million MEDLINE records. The associations between
      genes have been annotated by linking genes to terms from the medical subject
      heading (MeSH) index and terms from the gene ontology (GO) database. The
      extracted database and accompanying web tools for gene-expression analysis have
      collectively been named 'PubGene'. We validated the extracted networks by three
      large-scale experiments showing that co-occurrence reflects biologically
      meaningful relationships, thus providing an approach to extract and structure
      known biology. We validated the applicability of the tools by analyzing two
      publicly available microarray data sets.

PMID- 11326271
TI  - SOCS-1, a negative regulator of the JAK/STAT pathway, is silenced by methylation
      in human hepatocellular carcinoma and shows growth-suppression activity.
AB  - Hepatocellular carcinoma (HCC) is a major cause of cancer death, but the
      molecular mechanism for its development beyond its initiation has not been well
      characterized. Suppressor of cytokine signaling (SOCS-1; also known as JAB and
      SSI-1) switches cytokine signaling 'off' by means of its direct interaction with
      Janus kinase (JAK). We identified aberrant methylation in the CpG island of SOCS
      1 that correlated with its transcription silencing in HCC cell lines. The
      incidence of aberrant methylation was 65% in the 26 human primary HCC tumor
      samples analyzed. Moreover, the restoration of SOCS-1 suppressed both growth rate
      and anchorage-independent growth of cells in which SOCS-1 was methylation
      silenced and JAK2 was constitutively activated. This growth suppression was
      caused by apoptosis and was reproduced by AG490, a specific, chemical JAK2
      inhibitor that reversed constitutive phosphorylation of STAT3 in SOCS-1
      inactivated cells. The high prevalence of the aberrant SOCS-1 methylation and its
      growth suppression activity demonstrated the importance of the constitutive
      activation of the JAK/STAT pathway in the development of HCC. Our results also
      indicate therapeutic strategies for the treatment of HCC including use of SOCS-1
      in gene therapy and inhibition of JAK2 by small molecules, such as AG490.

PMID- 11326272
TI  - Heterozygous mutations in ANKH, the human ortholog of the mouse progressive
      ankylosis gene, result in craniometaphyseal dysplasia.
AB  - Craniometaphyseal dysplasia (CMD) is a bone dysplasia characterized by overgrowth
      and sclerosis of the craniofacial bones and abnormal modeling of the metaphyses
      of the tubular bones. Hyperostosis and sclerosis of the skull may lead to cranial
      nerve compressions resulting in hearing loss and facial palsy. An autosomal
      dominant form of the disorder (MIM 123000) was linked to chromosome 5p15.2-p14.1
      (ref. 3) within a region harboring the human homolog (ANKH) of the mouse
      progressive ankylosis (ank) gene. The ANK protein spans the outer cell membrane
      and shuttles inorganic pyrophosphate (PPi), a major inhibitor of physiologic and
      pathologic calcification, bone mineralization and bone resorption. Here we carry
      out mutation analysis of ANKH, revealing six different mutations in eight of nine
      families. The mutations predict single amino acid substitutions, deletions or
      insertions. Using a helix prediction program, we propose for the ANK molecule 12
      membrane-spanning helices with an alternate inside/out orientation and a central
      channel permitting the passage of PPi. The mutations occur at highly conserved
      amino acid residues presumed to be located in the cytosolic portion of the
      protein. Our results link the PPi channel ANK with bone formation and remodeling.

PMID- 11326273
TI  - Susceptibility to mouse cytomegalovirus is associated with deletion of an
      activating natural killer cell receptor of the C-type lectin superfamily.
AB  - Cytomegalovirus is the leading cause of congenital viral disease and the most
      important opportunistic infection in immunocompromised patients. We have used a
      mouse experimental infection model (MCMV) to study the genetic parameters of
      host/virus interaction. Susceptibility to infection with MCMV is controlled by
      Cmv1, a chromosome 6 locus that regulates natural killer (NK) cell activity
      against virally infected targets. Here, we use a positional cloning strategy to
      isolate the gene mutated at the Cmv1 locus. Cmv1 maps within a 0.35-cM interval
      defined by markers D6Ott8 and D6Ott115, which corresponds to a physical distance
      of 1.6 Mb (refs. 6-8). A transcript map of the region identified 19 genes,
      including members of the killer cell lectin-like receptor family a (Klra,
      formerly Ly49; refs. 9-12), which encode inhibitory or activating NK cell
      receptors that interact with MHC class I molecules. Klra genes have different
      copy numbers and genomic organization, and are highly polymorphic among inbred
      strains, making it difficult to distinguish between normal allelic variants and
      distinct Klra genes, or possible mutations associated with Cmv1. The recombinant
      inbred strain BXD-8/Ty (BXD-8; ref. 18), derived from Cmv1r C57BL/6 (B6,
      resistant) and Cmv1s DBA/2 (susceptible), is of particular interest because it is
      highly susceptible to MCMV infection despite having a B6 haplotype at Cmv1. We
      determined that MCMV susceptibility in BXD-8 is associated with the deletion of
      Klra8 (formerly Ly49h).

PMID- 11326274
TI  - First genetic evidence of GABA(A) receptor dysfunction in epilepsy: a mutation in
      the gamma2-subunit gene.
AB  - Major advances in the identification of genes implicated in idiopathic epilepsy
      have been made. Generalized epilepsy with febrile seizures plus (GEFS+), benign
      familial neonatal convulsions and nocturnal frontal lobe epilepsy, three
      autosomal dominant idiopathic epilepsies, result from mutations affecting voltage
      gated sodium and potassium channels, and nicotinic acetylcholine receptors,
      respectively. Disruption of GABAergic neurotransmission mediated by gamma
      aminobutyric acid (GABA) has been implicated in epilepsy for many decades. We now
      report a K289M mutation in the GABA(A) receptor gamma2-subunit gene (GABRG2) that
      segregates in a family with a phenotype closely related to GEFS+ (ref. 8), an
      autosomal dominant disorder associating febrile seizures and generalized epilepsy
      previously linked to mutations in sodium channel genes. The K289M mutation
      affects a highly conserved residue located in the extracellular loop between
      transmembrane segments M2 and M3. Analysis of the mutated and wild-type alleles
      in Xenopus laevis oocytes confirmed the predicted effect of the mutation, a
      decrease in the amplitude of GABA-activated currents. We thus provide the first
      genetic evidence that a GABA(A) receptor is directly involved in human idiopathic
      epilepsy.

PMID- 11326275
TI  - Mutant GABA(A) receptor gamma2-subunit in childhood absence epilepsy and febrile
      seizures.
AB  - Epilepsies affect at least 2% of the population at some time in life, and many
      forms have genetic determinants. We have found a mutation in a gene encoding a
      GABA(A) receptor subunit in a large family with epilepsy. The two main phenotypes
      were childhood absence epilepsy (CAE) and febrile seizures (FS). There is a
      recognized genetic relationship between FS and CAE, yet the two syndromes have
      different ages of onset, and the physiology of absences and convulsions is
      distinct. This suggests the mutation has age-dependent effects on different
      neuronal networks that influence the expression of these clinically distinct, but
      genetically related, epilepsy phenotypes. We found that the mutation in GABRG2
      (encoding the gamma2-subunit) abolished in vitro sensitivity to diazepam, raising
      the possibility that endozepines do in fact exist and have a physiological role
      in preventing seizures.

PMID- 11326276
TI  - Beta-catenin-sensitive isoforms of lymphoid enhancer factor-1 are selectively
      expressed in colon cancer.
AB  - Constitutive activation of the Wnt signaling pathway is a root cause of many
      colon cancers. Activation of this pathway is caused by genetic mutations that
      stabilize the beta-catenin protein, allowing it to accumulate in the nucleus and
      form complexes with any member of the lymphoid enhancer factor (LEF1) and T-cell
      factor (TCF1, TCF3, TCF4) family of transcription factors (referred to
      collectively as LEF/TCFs) to activate transcription of target genes. Target genes
      such as MYC, CCND1, MMP7 and TCF7 (refs. 5-9) are normally expressed in colon
      tissue, so it has been proposed that abnormal expression levels or patterns
      imposed by beta-catenin/TCF complexes have a role in tumor progression. We report
      here that LEF1 is a new type of target gene ectopically activated in colon
      cancer. The pattern of this ectopic expression is unusual because it derives from
      selective activation of a promoter for a full-length LEF1 isoform that binds beta
      catenin, but not a second, intronic promoter that drives expression of a dominant
      negative isoform. beta-catenin/TCF complexes can activate the promoter for full
      length LEF1, indicating that in cancer high levels of these complexes misregulate
      transcription to favor a positive feedback loop for Wnt signaling by inducing
      selective expression of full-length, beta-catenin-sensitive forms of LEF/TCFs.

PMID- 11326277
TI  - Tas1r3, encoding a new candidate taste receptor, is allelic to the sweet
      responsiveness locus Sac.
AB  - The ability to taste the sweetness of carbohydrate-rich foodstuffs has a critical
      role in the nutritional status of humans. Although several components of bitter
      transduction pathways have been identified, the receptors and other sweet
      transduction elements remain unknown. The Sac locus in mouse, mapped to the
      distal end of chromosome 4 (refs. 7-9), is the major determinant of differences
      between sweet-sensitive and -insensitive strains of mice in their responsiveness
      to saccharin, sucrose and other sweeteners. To identify the human Sac locus, we
      searched for candidate genes within a region of approximately one million base
      pairs of the sequenced human genome syntenous to the region of Sac in mouse. From
      this search, we identified a likely candidate: T1R3, a previously unknown G
      protein-coupled receptor (GPCR) and the only GPCR in this region. Mouse Tas1r3
      (encoding T1r3) maps to within 20,000 bp of the marker closest to Sac (ref. 9)
      and, like human TAS1R3, is expressed selectively in taste receptor cells. By
      comparing the sequence of Tas1r3 from several independently derived strains of
      mice, we identified a specific polymorphism that assorts between taster and non
      taster strains. According to models of its structure, T1r3 from non-tasters is
      predicted to have an extra amino-terminal glycosylation site that, if used, would
      interfere with dimerization.

PMID- 11326278
TI  - Regulation of endocytosis by CUP-5, the Caenorhabditis elegans mucolipin-1
      homolog.
AB  - Loss of the human mucolipin-1 gene underlies mucolipidosis type IV (MLIV), a
      lysosomal storage disease that results in severe developmental neuropathology.
      Unlike other lysosomal storage diseases, MLIV is not associated with a lack of
      lysosomal hydrolases; instead, MLIV cells display abnormal endocytosis of lipids
      and accumulate large vesicles, indicating that a defect in endocytosis may
      underlie the disease. Here we report the identification of a loss-of-function
      mutation in the Caenorhabditis elegans mucolipin-1 homolog, cup-5, and show that
      this mutation results in an enhanced rate of uptake of fluid-phase markers,
      decreased degradation of endocytosed protein and accumulation of large vacuoles.
      Overexpression of cup-5(+) causes the opposite phenotype, indicating that cup-5
      activity controls aspects of endocytosis. Studies in model organisms such as C.
      elegans have helped illuminate fundamental mechanisms involved in normal cellular
      function and human disease; thus the C. elegans cup-5 mutant may be a useful
      model for studying conserved aspects of mucolipin-1 structure and function and
      for assessing the effects of potential therapeutic compounds.

PMID- 11326279
TI  - The gene defective in leukocyte adhesion deficiency II encodes a putative GDP
      fucose transporter.
AB  - Leukocyte adhesion deficiency II (LAD II) is characterized by the lack of
      fucosylated glycoconjugates, including selectin ligands, causing immunodeficiency
      and severe mental and growth retardation. No deficiency in fucosyltransferase
      activities or in the activities of enzymes involved in GDP-fucose biosynthesis
      has been found. Instead, the transport of GDP-fucose into isolated Golgi vesicles
      of LAD II cells appeared to be reduced. To identify the gene mutated in LAD II,
      we cloned 12 cDNAs from Caenorhabditis elegans, encoding multi-spanning
      transmembrane proteins with homology to known nucleotide sugar transporters, and
      transfected them into fibroblasts from an LAD II patient. One of these clones re
      established expression of fucosylated glycoconjugates with high efficiency and
      allowed us to identify a human homolog with 55% identity, which also directed re
      expression of fucosylated glycoconjugates. Both proteins were localized to the
      Golgi. The corresponding endogenous protein in LAD II cells had an R147C amino
      acid change in the conserved fourth transmembrane region. Overexpression of this
      mutant protein in cells from a patient with LAD II did not rescue fucosylation,
      demonstrating that the point mutation affected the activity of the protein. Thus,
      we have identified the first putative GDP-fucose transporter, which has been
      highly conserved throughout evolution. A point mutation in its gene is
      responsible for the disease in this patient with LAD II.

PMID- 11326280
TI  - Complementation cloning identifies CDG-IIc, a new type of congenital disorders of
      glycosylation, as a GDP-fucose transporter deficiency.
AB  - Congenital disorders of glycosylation (CDG) comprise a rapidly growing group of
      inherited disorders in which glycosylation of glycoproteins is defective due to
      mutations in genes required for the assembly of lipid-linked oligosaccharides,
      their transfer to nascent glycoproteins (CDG-I) or the processing of protein
      bound glycans (CDG-II). Previously' a defect in the GDP-fucose import into the
      lumen of the Golgi was identified in a person with CDG (A.C.) with a general
      deficiency of fucosyl residues in glycoproteins. This patient presents the
      clinical features of leukocyte adhesion deficiency type II (LAD II) including
      mental retardation, short stature, facial stigmata, and recurrent bacterial
      peripheral infections with persistently elevated peripheral leukocytes. Using a
      fucose-specific, lectin-staining procedure for detection of fucosylated
      glycoproteins and a retroviral cDNA library, we isolated a cDNA complementing the
      fucosylation defect in the patient's fibroblasts. The cDNA encodes a highly
      hydrophobic protein of 364 amino acids with multiple putative transmembrane
      domains. Restoration of GDP-fucose import activity in Golgi-enriched vesicles
      from the patient's fibroblasts verified the GDP-fucose transporter activity of
      this protein. We identified two missense mutations in the GDP-fucose transporter
      cDNA of patient A.C. and of two other people with LAD II. Thus complementation
      cloning allowed us to identify the human GDP-fucose transporter cDNA and GDP
      fucose transporter deficiency as a cause for a new type of CDG. Following the
      recent recommendations for the nomenclature for CDG, this new type is classified
      as CDG-IIc (formerly LAD II).

PMID- 11326281
TI  - Transposable B2 SINE elements can provide mobile RNA polymerase II promoters.
AB  - Short interspersed elements (SINEs) are highly abundant components of mammalian
      genomes that are propagated by retrotransposition. SINEs are recognized as a
      causal agent of human disease and must also have had a profound influence in
      shaping eukaryotic genomes. The B2 SINE family constitutes approximately 0.7% of
      total mouse genomic DNA (ref. 2) and is also found at low abundance in humans. It
      resembles the Alu family in several respects, such as its mechanism of
      propagation. B2 SINEs are derived from tRNA and are transcribed by RNA polymerase
      (pol) III to generate short transcripts that are not translated. We find here,
      however, that one B2 SINE also carries an active pol II promoter located outside
      the tRNA region. Indeed, a B2 element is responsible for the production of a
      mouse Lama3 transcript. The B2 pol II promoters can be bound and stimulated by
      the transcription factor USF (for upstream stimulatory factor), as shown by
      transient transfection experiments. Moreover, this pol II activity does not
      preclude the pol III transcription necessary for retrotransposition. Dispersal of
      B2 SINEs by retrotransposition may therefore have provided numerous opportunities
      for creating regulated pol II transcription at novel genomic sites. This
      mechanism may have allowed the evolution of new transcription units and new
      genes.

PMID- 11326282
TI  - Haploinsufficiency of protamine-1 or -2 causes infertility in mice.
AB  - Protamines are the major DNA-binding proteins in the nucleus of sperm in most
      vertebrates and package the DNA in a volume less than 5% of a somatic cell
      nucleus. Many mammals have one protamine, but a few species, including humans and
      mice, have two. Here we use gene targeting to determine if the second protamine
      provides redundancy to an essential process, or if both protamines are necessary.
      We disrupted the coding sequence of one allele of either Prm1 or Prm2 in
      embryonic stem (ES) cells derived from 129-strain mice, and injected them into
      blastocysts from C57BL/6-strain mice. Male chimeras produced 129-genotype sperm
      with disrupted Prm1 or Prm2 alleles, but failed to sire offspring carrying the
      129 genome. We also found that a decrease in the amount of either protamine
      disrupts nuclear formation, processing of protamine-2 and normal sperm function.
      Our studies show that both protamines are essential and that haploinsufficiency
      caused by a mutation in one allele of Prm1 or Prm2 prevents genetic transmission
      of both mutant and wild-type alleles.

PMID- 11326283
TI  - A susceptibility locus for asthma-related traits on chromosome 7 revealed by
      genome-wide scan in a founder population.
AB  - The genetics of asthma and atopy have been difficult to determine because these
      diseases are genetically heterogeneous and modified by environment. The pedigrees
      in our study (n=86) originate in eastern central Finland (Kainuu province).
      According to census records, this region had only 200 households (2,000
      inhabitants) in the mid sixteenth to mid seventeenth centuries. The current
      population of 100,000 represents the expansion of these founders within the past
      400 years. Because this population is relatively homogeneous, we hypothesized
      that the molecular genetic mechanisms underlying asthma might also have reduced
      heterogeneity and therefore be easier to dissect than in mixed populations. A
      recent twin family study supported a strong genetic component for asthma in
      Finland. We carried out a genome-wide scan for susceptibility loci in asthma in
      the Kainuu subpopulation. We identified two regions of suggestive linkage and
      studied them further with higher-density mapping. We obtained evidence for
      linkage in a 20-cM region of chromosome 7p14-p15 for three phenotypes: asthma, a
      high level of immunoglobulin E (IgE; atopy) and the combination of the
      phenotypes. The strongest linkage was seen for high serum IgE (non-parametric
      linkage (NPL) score 3.9, P=0.0001), exceeding the threshold for genome-wide
      significance based on simulations. We also observed linkage between this locus
      and asthma or atopy in two independent data sets.

PMID- 11326289
TI  - Nerve terminals contacting a monoaminergic neuron.

PMID- 11326284
TI  - Gene therapy restores vision in a canine model of childhood blindness.
AB  - The relationship between the neurosensory photoreceptors and the adjacent retinal
      pigment epithelium (RPE) controls not only normal retinal function, but also the
      pathogenesis of hereditary retinal degenerations. The molecular bases for both
      primary photoreceptor and RPE diseases that cause blindness have been identified.
      Gene therapy has been used successfully to slow degeneration in rodent models of
      primary photoreceptor diseases, but efficacy of gene therapy directed at
      photoreceptors and RPE in a large-animal model of human disease has not been
      reported. Here we study one of the most clinically severe retinal degenerations,
      Leber congenital amaurosis (LCA). LCA causes near total blindness in infancy and
      can result from mutations in RPE65 (LCA, type II; MIM 180069 and 204100). A
      naturally occurring animal model, the RPE65-/- dog, suffers from early and severe
      visual impairment similar to that seen in human LCA. We used a recombinant adeno
      associated virus (AAV) carrying wild-type RPE65 (AAV-RPE65) to test the efficacy
      of gene therapy in this model. Our results indicate that visual function was
      restored in this large animal model of childhood blindness.

PMID- 11326290
TI  - Dissociating anxiety from pain: mapping the neuronal marker N-acetyl aspartate to
      perception distinguishes closely interrelated characteristics of chronic pain.

PMID- 11326291
TI  - Possible influence of the insertion/deletion polymorphism in the angiotensin I
      converting enzyme gene on therapeutic outcome in affective disorders.

PMID- 11326292
TI  - Mutation screening of the KCNN3 gene reveals a rare frameshift mutation.

PMID- 11326293
TI  - Dopamine D(2)/D(3)-receptor and transporter densities in nucleus accumbens and
      amygdala of type 1 and 2 alcoholics.
AB  - Alcohol acts through mechanisms involving the brain neurotransmitter dopamine
      (DA) with the nucleus accumbens as the key zone for mediating these effects. We
      evaluated the densities of DA D(2)/D(3) receptors and transporters in the nucleus
      accumbens and amygdala of post-mortem human brains by using [(125)l]epidepride
      and [(125)I]PE2I as radioligands in whole hemispheric autoradiography of
      Cloninger type 1 and 2 alcoholics and healthy controls. When compared with
      controls, the mean binding of [(125)I]epidepride to DA D(2)/D(3) receptors was
      20% lower in the nucleus accumbens and 41% lower in the amygdala, and
      [(125)I]PE2I binding to DA transporters in the nucleus accumbens was 39% lower in
      type 1 alcoholics. These data indicate that dopaminergic functions in these
      limbic areas may be impaired among type 1 alcoholics, due to the substantially
      lower number of receptor sites. Our results suggest that such a reduction may
      result in the chronic overuse of alcohol as an attempt to stimulate DA function.

PMID- 11326294
TI  - Suicide attempts and the tryptophan hydroxylase gene.
AB  - Tryptophan hydroxylase (TPH) is the rate-limiting enzyme of serotonin synthesis.
      In this case-control study, we investigated whether the TPH gene was a
      susceptibility factor for suicidal behavior. Seven polymorphisms spanning the
      entire gene were studied in a case-control study including 231 individuals who
      had attempted suicide and 281 controls. Significant associations were found
      between variants in introns 7, 8 and 9 (chi(2) = 11.2, df = 1, P< 0.0008 for the
      allele distribution; these loci are in complete linkage disequilibrium) and in
      the 3' noncoding region (chi(2) = 30.94, P = 0.0014) and suicide attempt. The
      association was strongest for subjects who had attempted suicide by violent means
      and who had a history of major depression. No significant association was
      observed between suicide attempts and polymorphisms in the promoter, intron 1 and
      intron 3. The results presented here, and those of previous studies, suggest that
      a genetic variant of the 3' part of the TPH gene may be a susceptibility factor
      for a phenotype combining suicidal behavior, mood disorder and impulsive
      aggression.

PMID- 11326295
TI  - Identification of single nucleotide polymorphisms (SNPs) and other sequence
      changes and estimation of nucleotide diversity in coding and flanking regions of
      the NMDAR1 receptor gene in schizophrenic patients.
AB  - Glutamatergic dysregulation has been hypothesized to play a role in
      schizophrenia. The N-methyl-D-aspartate (NMDA) type of glutamate receptor
      especially is of interest because, in addition to binding sites for glutamate and
      glycine, a necessary co-agonist, this receptor also contains noncompetitive
      binding sites for the psychotomimetics phencyclidine (PCP), MK-801, and ketamine.
      PCP-induced psychosis has been a useful disease model in that both the positive
      as well as the negative symptomatologies seen in schizophrenia are observed.
      Recently, a mouse deficient in expression of the NR1 subunit gene (NMDAR1) of the
      heteromeric receptor has been developed and shown to display aberrant behaviors,
      with reduced social and sexual interactions as well as increased stereotypic
      motor activity. In an extensive examination of the NMDAR1 gene in our laboratory
      in approximately 100 chronic schizophrenic patients, 28 unique sequence changes
      were identified, including eight single nucleotide polymorphisms (SNPs) in the 5'
      untranslated region (5'UTR), six SNPs in coding regions (cSNPs), eleven intronic
      SNPs, two intronic deletions of 7 and 30 bp, and an intronic
      microinsertion/deletion. With the exception of one previously reported cSNP, all
      of the identified changes were novel. The frequency of polymorphisms differed
      significantly by ethnicity and several appeared to be in linkage disequilibrium.
      None of the changes appeared likely to be of functional significance, thus
      suggesting that changes in the genomic NMDAR1 are unlikely to contribute to the
      etiology of schizophrenia. Estimates of nucleotide diversity are comparable to
      those observed in studies of other genes.

PMID- 11326296
TI  - Developmental and stress-related changes of neurotrophic factor gene expression
      in an animal model of schizophrenia.
AB  - The neonatal (PND 7) lesion of the ventral hippocampus (VH) with ibotenic acid
      represents a well-established experimental paradigm that recapitulates many
      schizophrenia-like phenomena. In order to investigate molecular changes that
      could contribute to long lasting consequences on brain function, we have
      investigated the effects of the VH lesion on the expression for the trophic
      factors FGF-2 and BDNF. We used RNase protection assay to measure their mRNA
      levels in cortical regions of prepubertal (PND 35) and young adult (PND 56)
      animals, both under basal condition as well as in response to an acute restraint
      stress. The expression of BDNF was not altered by the VH lesion in prefrontal
      (PFC) and frontal cortex (FC) of PND 35 or PND 56 rats. An acute restraint stress
      at PND 35 produced a significant increase of the neurotrophin expression in PFC
      of sham as well as lesioned animals. However in young adult animals a significant
      elevation of BDNF expression was observed only in sham rats. We also found that
      the VH lesion produced a significant reduction of basal BDNF mRNA levels in the
      cingulate cortex of young adult, but not prepubertal rats. This effect was not
      accompanied by changes in the acute modulation of the neurotrophin, which was up
      regulated by stress in both experimental groups. Conversely the expression of FGF
      2 at PND 35 and PND 56 was not altered by early postnatal VH lesion, and there
      were no major differences between sham and lesioned animals in response to the
      acute stress. The changes in trophic factor expression may be relevant for the
      long-term effects of VH lesion on synaptic plasticity and may determine an
      increased vulnerability of the brain under challenging situations.

PMID- 11326297
TI  - Disease-specific changes in regulator of G-protein signaling 4 (RGS4) expression
      in schizophrenia.
AB  - Complex defects in neuronal signaling may underlie the dysfunctions that
      characterize schizophrenia. Using cDNA microarrays, we discovered that the
      transcript encoding regulator of G-protein signaling 4 (RGS4) was the most
      consistently and significantly decreased in the prefrontal cortex of all
      schizophrenic subjects examined. The expression levels of ten other RGS family
      members represented on the microarrays were unchanged and hierarchical data
      analysis revealed that as a group, 274 genes associated with G-protein signaling
      were unchanged. Quantitative in situ hybridization verified the microarray RGS4
      data, and demonstrated highly correlated decreases in RGS4 expression across
      three cortical areas of ten subjects with schizophrenia. RGS4 expression was not
      altered in the prefrontal cortex of subjects with major depressive disorder or in
      monkeys treated chronically with haloperidol. Interestingly, targets for 70 genes
      mapped to the major schizophrenia susceptibility locus 1q21--22 were present on
      the microarrays, of which only RGS4 gene expression was consistently altered. The
      combined data indicate that a decrease in RGS4 expression may be a common and
      specific feature of schizophrenia, which could be due either to genetic factors
      or a disease- specific adaptation, both of which could affect neuronal signaling.

PMID- 11326298
TI  - A missense mutation in a novel gene encoding a putative cation channel is
      associated with catatonic schizophrenia in a large pedigree.
AB  - Schizophrenia is a common and etiologically heterogeneous disorder. Although
      inheritance of schizophrenic syndromes is complex with genetic and environmental
      factors contributing to the clinical phenotype, periodic catatonia, a familial
      subtype of catatonic schizophrenia, appears to be transmitted in an autosomal
      dominant manner. We report here that a Leu309Met mutation in WKL1, a positional
      candidate gene on chromosome 22q13.33 encoding a putative non-selective cation
      channel expressed exclusively in brain, co-segregates with periodic catatonia in
      an extended pedigree. Structural analyses revealed that this missense mutation
      results in conformational changes of the mutant protein. Our results not only
      underscore the importance of genetic mechanisms in the etiology of schizophrenic
      syndromes, but also provide a better understanding of the pathogenesis and
      incapacitating course of catatonic schizophrenia and related disorders.

PMID- 11326299
TI  - Schizophrenic women with the APOE epsilon 4 allele have a worse prognosis than
      those without it.
AB  - The epsilon 4 allele of APOE is generally accepted to be a risk factor in
      Alzheimer's disease and it has been related to other neuropsychiatric disorders,
      including schizophrenia. The results of several case-control studies have been
      inconclusive. To shed more light on this issue we carried out an association
      study that compared the APOE common variant in a group of 365 schizophrenia
      patients and 584 controls. We found no differences in the genotype distributions
      and allele frequencies of patients and controls. In the group of patients, we
      also analysed the possible influence of the epsilon 4 allele in the clinical
      variables. The most important findings are that the age at onset (AAO) of epsilon
      4+ schizophrenic women, those that have one or two epsilon 4 alleles, is 4 years
      earlier than that of epsilon 4- women and their risk of suffering a negative
      syndrome subtype is four times greater. This was not found in schizophrenic men.
      Our results show that the APOE variant is not a risk factor for developing
      schizophrenia but that it may modulate its phenotypic expression in a sex
      dependent manner.

PMID- 11326300
TI  - The genomic organisation of the metabotropic glutamate receptor subtype 5 gene,
      and its association with schizophrenia.
AB  - The G-protein coupled metabotropic glutamate receptors (GRMs/mGluRs) have been
      implicated in the aetiology of schizophrenia as they modulate the NMDA response
      and that of other neurotransmitters including dopamine and GABA.(1-3)
      Electrophysiological studies in GRM subtype 5 knockout mice reveal, in one study,
      a sensorimotor gating deficit characteristic of schizophrenia and in another, a
      key role for this gene in the modulation of hippocampal NMDA-dependent synaptic
      plasticity. In humans, GRM5 levels are increased in certain pyramidal cell
      neurons in schizophrenics vs controls.(6) Finally, GRM5 has been mapped to 11q14,
      neighbouring a translocation that segregates with schizophrenia and related
      psychoses in a large Scottish family, F23 (MLOD score 6.0). We determined the
      intron/exon structure of GRM5 and identified a novel intragenic microsatellite. A
      case-control association study identified a significant difference in allele
      frequency distribution between schizophrenics and controls (P = 0.04). This is
      suggestive of involvement of the GRM5 gene in schizophrenia in this population.

PMID- 11326301
TI  - Exon 3 of tyrosine hydroxylase gene: lack of association with Japanese
      schizophrenic patients.
AB  - Tyrosine hydroxylase (TH) is the rate-limiting enzyme in dopamine (DA)
      biosynthesis. Exon 3 of the human TH gene encodes the sequence from Ser31 to
      Glu104 of type 1 enzyme, which contains the critical parts for regulation of the
      catalytic activity. The amino acid residues Gly36-Arg37-Arg38 were identified as
      a key sequence for DA to exert its inhibitory effect on catalytic activity.
      Therefore, we screened the nucleotide sequences of exon 3 from 201 Japanese
      patients with schizophrenia to explain the elevation in the synaptic or
      presynaptic DA concentrations in the schizophrenic brain, based on the hypothesis
      that any mutation changing the amino acid sequence Gly36-Arg37-Arg38 would result
      in the elevation of DA synthesis, due to a reduced inhibitory effect of DA on the
      catalytic activity. However, no mutated sequences of exon 3 and both exon-intron
      boundaries were detected in any of the patients examined. Polymorphisms
      generating Val81 and Met81 were compared of the distributions of genotype and
      allele between the patients and 175 Japanese healthy controls, which did not
      suggest an association between the polymorphism and schizophrenia. These results
      indicate that exon 3 of the human TH gene lacks association with schizophrenia in
      Japanese patients.

PMID- 11326302
TI  - Identification of sequence variants and analysis of the role of the glycogen
      synthase kinase 3 beta gene and promoter in late onset Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a disorder characterised by a progressive
      deterioration in memory and other cognitive functions. Glycogen synthase kinase 3
      beta (GSK3 beta) phosphorylates the microtubule associated protein tau at sites
      that are aberrantly phosphorylated in AD. GSK3 beta binds to presenilin 1 and
      plays a role in wnt and insulin signalling cascades, both of which have been
      proposed to be linked to AD. Moreover GSK3 beta activity may be altered in AD
      brain. These observations suggest a central role for GSK3 beta in AD and led us
      to investigate GSK3 beta as a candidate gene for AD. We sought to identify
      sequence variations in the gene and its promoter, as these could have an effect
      on activity and expression leading to abnormal function. Sequencing over 3000 bp
      of the GSK3 beta putative promoter revealed there to be five sequence variations,
      two of which were common (>10%). However on further examination none of these,
      either alone or in synergy, had any association with late onset AD.
      Stratification of the data by APOE epsilon 4 status also produced no significant
      association. Sequencing of the GSK3 beta coding region revealed no variations.
      This would suggest that the aberrant phosphorylation of tau by GSK3 beta in AD is
      not due to sequence variations in the gene or its promoter.

PMID- 11326303
TI  - Association between an agouti-related protein gene polymorphism and anorexia
      nervosa.
AB  - Anorexia nervosa (AN) is a life threatening disorder affecting mostly adolescent
      women. It is a dramatic psychiatric syndrome accompanied by severe weight loss,
      hyperactivity and neuroendocrine changes (reviewed in Refs 1 and 2). Several
      studies have shown a strong genetic component in AN (reviewed in Ref 3). Recent
      advances in unraveling the mechanisms of weight control point to a crucial role
      of the melanocortin-4 receptor (MC4-r) system in regulating body weight. The
      orexigenic neuropeptide agouti-related protein (AGRP), a MC4-r antagonist, plays
      a crucial role in maintaining body weight, by inducing food intake. The sequence
      of the coding region of the human AGRP gene (AGRP) was determined and the AGRP of
      100 patients with AN was screened for variations. Three single nucleotide
      polymorphisms (SNPs) were identified and screened in a further 45 patients and
      244 controls. Two alleles were in complete linkage disequilibrium and were
      significantly enriched in anorectic patients (11%; P = 0.015) compared to
      controls (4.5%). These data indicate that variations of AGRP are associated with
      susceptibility for AN. This is possibly caused by defective suppression of the
      MC4-r by the variant AGRP, leading to a decreased feeding signal, increasing the
      risk of developing AN. These results implicate that antagonism of the MC4-r might
      be considered as pharmacotherapy for patients with AN.

PMID- 11326304
TI  - Low avidity of human serum antibodies for Borna disease virus antigens questions
      their diagnostic value.
AB  - Borna disease virus (BDV) can induce neurological disease in animals. Since viral
      nucleic acid, infectious particles and antibodies recognizing BDV antigens were
      found at higher frequencies in psychiatric patients than in healthy controls, BDV
      is suspected to cause psychiatric disorders in humans. However, the human origin
      of these viruses has recently been questioned. To diagnose BDV infections, sera
      are usually analyzed for antiviral antibodies by indirect immunofluorescence
      (IFA) on virus-infected cells. This study reveals that the reactive antibodies in
      human sera mainly recognized the BDV phosphoprotein, whereas animal sera
      preferentially detected the viral nucleoprotein. Immunoglobulin (Ig) G in sera of
      experimentally or naturally infected animals bound to the viral antigen with high
      avidity, ie resisting 3 M urea, whereas reactive IgG in human sera did not.
      Longitudinal studies showed that reactive human antibodies persisted for many
      years without gaining high avidity for BDV antigens, indicating that they were
      probably not induced by BDV but rather by infection with an antigenically related
      microorganism of unknown identity or by exposure to other related immunogens.

PMID- 11326305
TI  - Attention-deficit hyperactivity disorder and the adrenergic receptors alpha 1C
      and alpha 2C.
AB  - The adrenergic system has been hypothesized to be involved in the etiology of
      attention-deficit hyperactivity disorder (ADHD) based on pharmacological
      interventions and animal models. Noradrenergic neurons are implicated in the
      modulation of vigilance, improvement of visual attention, initiation of adaptive
      response, learning and memory. In this study we tested the genes for two
      adrenergic receptors, alpha 1C (ADRA1C) located on chromosome 8p11.2, and alpha
      2C (ADRA2C) located on chromosome 4p16, as genetic susceptibility factors in
      ADHD. For the adrenergic receptor alpha 1C we used a C to T polymorphism that
      results in a change of Cys to Arg at codon 492 for the linkage study. For the
      adrenergic receptor alpha 2C gene we examined a dinucleotide repeat polymorphism
      located approximately 6 kb from the gene. We examined these polymorphisms in a
      sample of 103 families ascertained through an ADHD proband. Using the
      transmission disequilibrium test, we did not observe biased transmission of any
      of the alleles of these polymorphisms. We conclude that the alleles at the
      polymorphisms tested in these two genes are not linked to the ADHD phenotype in
      this sample of families.

PMID- 11326306
TI  - Association between violent suicidal behavior and the low activity allele of the
      serotonin transporter gene.
AB  - There is compelling evidence that serotonin system dysfunction is associated with
      certain behavioral disorders, such as suicidal behavior and impulsive aggression.
      A functional polymorphism in the promoter region of the serotonin transporter
      gene (5-HTTLPR) was recently identified and the presence of the short allele
      found to be associated with a lower level of expression of the gene, lower levels
      of 5-HT uptake, suicidal behavior and anxiety-related traits. We genotyped 51
      West European Caucasians who had made violent suicide attempts and 139 controls
      of the same ethnic origin, with no history of suicidal behavior. The frequencies
      of the S allele and the SS genotype were significantly higher in the violent
      suicide attempters than in the controls. The odds ratio for the SS genotype vs
      the LL genotype was 3.63 (95% CI (1.27--10.40)). This suggests that a change in
      expression of the gene encoding the 5-HT transporter may be involved in violent
      suicidal behavior.

PMID- 11326307
TI  - A possible susceptibility locus for bipolar affective disorder in chromosomal
      region 10q25--q26.
AB  - In an attempt to identify susceptibility loci for bipolar affective disorder, we
      are currently conducting a systematic genome screen with highly polymorphic
      microsatellite markers at an average marker spacing of 10 cM in a series of 75
      families, comprising 66 families from Germany, eight families from Israel, and
      one family from Italy. The families were ascertained through index cases with
      bipolar affective disorder. The distribution of diagnoses is as follows: 126
      individuals with bipolar I disorder, 40 with bipolar II disorder, 14 with
      schizoaffective disorder of the bipolar type, 40 individuals with recurrent
      unipolar depression, 51 with a minor psychiatric diagnosis, and two individuals
      with a diagnosis of schizophrenia. One hundred and seventy-one individuals are
      unaffected. Here, we present results from chromosome 10. Linkage analyses using a
      total of 33 microsatellite markers with parametric and non-parametric methods
      provided evidence for linkage at chromosomal region 10q25--q26. The highest two
      point LOD score (2.86, theta = 0.05) was obtained for D10S217 using a dominant
      genetic model and a broad definition of affection status. The GENEHUNTER program
      localized the putative susceptibility locus within a ca 15-cM interval between
      markers D10S1483 and D10S217 with a maximum NPL(all) score of 3.12 (P = 0.0013).
      Positive linkage findings that have been reported by two independent studies
      further support the hypothesis of a susceptibility gene for bipolar affective
      disorder on 10q25-q26.

PMID- 11326308
TI  - Allelic variation of serotonin transporter expression is associated with
      depression in Parkinson's disease.
AB  - Idiopathic Parkinson's disease (PD) is a common neurodegenerative disorder with
      prominent motor symptoms. However, depression is common in PD, affecting about
      40% of PD patients. Since there is extensive evidence of degeneration of
      serotonin (5HT) neurons and loss of the 5HT transporter (5HTT) in PD, we assessed
      whether a functional polymorphism in the promoter of the 5HTT gene (5HTT gene
      linked polymorphic region, 5HTTLPR), which determines high or low 5HT uptake, is
      associated with depressive symptomatology in PD patients. We found that patients
      with the short allele of the 5HTTLPR had significantly higher scores on the
      Hamilton Depression Scale. A functional promoter polymorphism of the monoamine
      oxidase A (MAOA) gene showed no association. Thus, the 5HTTLPR but not the MAOA
      gene promoter-associated polymorphism may be a risk factor for depression in PD
      patients, while neither polymorphism increases the risk for development of
      Parkinson's disease itself.

PMID- 11326310
TI  - Isolation of a novel human gene, MARKL1, homologous to MARK3 and its involvement
      in hepatocellular carcinogenesis.
AB  - Activation of the Wnt-signaling pathway is known to play a crucial role in
      carcinogenesis of various human organs including the colon, liver, prostate, and
      endometrium. To investigate the mechanisms underlying hepatocellular
      carcinogenesis, we attempted to identify genes regulated by beta-catenin/Tcf
      complex in a human hepatoma cell line, HepG2, in which an activated form of beta
      catenin is expressed. By means of cDNA microarray, we isolated a novel human
      gene, termed MARKL1 (MAP/microtubule affinity-regulating kinase-like 1), whose
      expression was downregulated in response to decreased Tcf/LEF1 activity. The
      transcript expressed in liver consisted of 3529 nucleotides that contained an
      open reading frame of 2256 nucleotides, encoding 752 amino acids homologous to
      human MARK3 (MAP/microtubule affinity-regulating kinase 3). Expression levels of
      MARKL1 were markedly elevated in eight of nine HCCs in which nuclear accumulation
      of beta-catenin were observed, which may suggest that MARKL1 plays some role in
      hepatocellular carcinogenesis.

PMID- 11326311
TI  - Cisplatinum and taxol induce different patterns of p53 phosphorylation.
AB  - Posttranslational modifications of p53 induced by two widely used anticancer
      agents, cisplatinum (DDP) and taxol were investigated in two human cancer cell
      lines. Although both drugs were able to induce phosphorylation at serine 20
      (Ser20), only DDP treatment induced p53 phosphorylation at serine 15 (Ser15).
      Moreover, both drug treatments were able to increase p53 levels and consequently
      the transcription of waf1 and mdm-2 genes, although DDP treatment resulted in a
      stronger inducer of both genes. Using two ataxia telangiectasia mutated (ATM)
      cell lines, the role of ATM in drug-induced p53 phosphorylations was
      investigated. No differences in drug-induced p53 phosphorylation could be
      observed, indicating that ATM is not the kinase involved in these phosphorylation
      events. In addition, inhibition of DNA-dependent protein kinase activity by
      wortmannin did not abolish p53 phosphorylation at Ser15 and Ser20, again
      indicating that DNA-PK is unlikely to be the kinase involved. After both taxol
      and DDP treatments, an activation of hCHK2 was found and this is likely to be
      responsible for phosphorylation at Ser20. In contrast, only DDP was able to
      activate ATR, which is the candidate kinase for phosphorylation of Ser15 by this
      drug. This data clearly suggests that differential mechanisms are involved in
      phosphorylation and activation of p53 depending on the drug type.

PMID- 11326312
TI  - Immunohistochemical detection of telomerase (hTERT) protein in human cancer
      tissues and a subset of cells in normal tissues.
AB  - We examined human telomerase reverse transcriptase (hTERT) protein distribution
      by immunohistochemistry in cultured cells and tissue sections. Cells with
      telomerase activity had nuclear positive signals whereas cells without telomerase
      activity did not. In most normal epithelial tissues, hTERT expression was
      prominent in the early proliferative descendent progenitors cells. In cancers
      with high telomerase activity, hTERT expression was detected in almost all
      neoplastic cells and correlated with telomerase activity levels, whereas cancers
      with low telomerase activity had fewer hTERT-positive cancer cells. In pediatric
      neuroblastomas with a favorable outcome, both the percentage of positive cells
      and the signal intensities of each hTERT-expressing cell decreased. These studies
      indicate that detection of telomerase at the cellular level is achievable and may
      have utility in cancer diagnostics.

PMID- 11326313
TI  - Jun N-terminal kinase 1 mediates transcriptional induction of matrix
      metalloproteinase 9 expression.
AB  - Tumor cell invasion and metastasis require precise coordination of adherence to
      extracellular matrix (ECM) and controlled degradation of its components. Invasive
      cells secrete proteolytic enzymes known as matrix metalloproteinases (MMPs) which
      degrade specific basement membrane molecules. Expression of these enzymes is
      regulated by multiple signaling mechanisms, including the mitogen-activated
      protein kinase (MAPK) pathway. One of the terminal effectors of this signaling
      cascade is jun N-terminal kinase 1 (JNK1) which phosphorylates the transcription
      factor c-jun, a component of the AP-1 complex. MMP-9 expression is regulated by
      two well-characterized AP-1 sites in the promoter of this gene. To determine how
      JNK1 activity regulated MMP-9 expression in human squamous cell carcinoma lines,
      we overexpressed this kinase in SCC25 cells. JNK1 overexpression induced MMP-9
      protein levels and activity in this cell line. Elevated MMP-9 expression
      correlated with increased invasion of reconstituted basement membranes by JNK1
      overexpressing clones. Site-directed mutagenesis of the MMP-9 promoter revealed
      that JNK1 cooperated with its transcription factor target c-jun to increase MMP-9
      expression at the transcriptional level via the proximal AP-1 site. These results
      suggest that elevated JNK1 expression may contribute to increased MMP-9 activity
      and ECM invasion by tumor cells.

PMID- 11326314
TI  - Expression of interleukin-8 correlates with angiogenesis, tumorigenicity, and
      metastasis of human prostate cancer cells implanted orthotopically in nude mice.
AB  - We determined whether the expression of interleukin-8 (IL-8) by human prostate
      cancer cells correlates with induction of angiogenesis, tumorigenicity, and
      production of metastasis. Low and high IL-8-producing clones were isolated from
      the heterogeneous PC-3 human prostate cancer cell line. The secretion of IL-8
      protein correlated with transcriptional activity and levels of IL-8 mRNA. All PC
      3 cells expressed both IL-8 receptors, CXCR1 and CXCR2. The low and high IL-8
      producing clones were injected into the prostate of nude mice. Titration studies
      indicated that PC-3 cells expressing high levels of IL-8 were highly tumorigenic,
      producing rapidly growing, highly vascularized prostate tumors with and a 100%
      incidence of lymph node metastasis. Low IL-8-expressing PC-3 cells were less
      tumorigenic, producing slower growing and less vascularized primary tumors and a
      significantly lower incidence of metastasis. In situ hybridization (ISH) analysis
      of the tumors for expression of genes that regulate angiogenesis and metastasis
      showed that the expression level of IL-8, matrix metalloproteinases, vascular
      endothelial growth factor (VEGF), and E-cadherin corresponded with microvascular
      density and biological behavior of the prostate cancers in nude mice.
      Collectively, the data show that the expression level of IL-8 in human prostate
      cancer cells is associated with angiogenesis, tumorigenicity, and metastasis.

PMID- 11326315
TI  - Profiling and verification of gene expression patterns in normal and malignant
      human prostate tissues by cDNA microarray analysis.
AB  - cDNA microarray technology allows the "profiling" of gene expression patterns for
      virtually any cellular material. In this study, we applied cDNA microarray
      technology to profile changes in gene expression associated with human prostate
      tumorigenesis. RNA prepared from normal and malignant prostate tissue was
      examined for the expression levels of 588 human genes. Four different methods for
      data normalization were utilized. Of these, normalization to ACTB expression
      proved to be the most rigorous technique with the least probability of producing
      spurious results. After normalization to ACTB expression, 15 of 588 (2.6%) genes
      examined by array analysis were differentially expressed by a factory of 2x or
      more in malignant compared to normal prostate tissues. The expression patterns
      for 8 of 15 genes have been reported previously in prostate tissues (TGFbeta3,
      TGFBR3, IGFII, IGFBP2, VEGF, FGF7, ERBB3, MYC), but those of seven genes are
      reported here for the first time (MLH1, CYP1B1, RFC4, EPHB3, MGST1, BTEB2, MLP).
      These genes describe at least four metabolic and signaling pathways likely
      disrupted in human prostate tumorigenesis. Reverse transcriptase polymerase chain
      reaction (RT-PCR) and Northern blot analyses quantitated with reference to ACTB
      expression levels verified the trends in gene expression levels observed by array
      analysis for 14/15 and 8/8 genes, respectively. However, RT-PCR and Northern blot
      analyses accurately verified the "fold" differences in expression levels for only
      6/15 (40%) and 7/8 (88%) of genes examined, respectively, demonstrating the need
      to better validate quantitative differences in gene expression revealed by array
      based techniques.

PMID- 11326316
TI  - Cyclooxygenase-2 pathway correlates with VEGF expression in head and neck cancer.
      Implications for tumor angiogenesis and metastasis.
AB  - We evaluated the role of COX-2 pathway in 35 head and neck cancers (HNCs) by
      analyzing COX-2 expression and prostaglandin E2 (PGE2) production in relation to
      tumor angiogenesis and lymph node metastasis. COX-2 activity was also correlated
      to vascular endothelial growth factor (VEGF) mRNA and protein expression. COX-2
      mRNA and protein expression was higher in tumor samples than in normal mucosa.
      PGE2 levels were higher in the tumor front zone in comparison with tumor core and
      normal mucosa (P<.0001). Specimens from patients with lymph node metastasis
      exhibited higher COX-2 protein expression (P=.0074), PGE2 levels (P=.0011) and
      microvessel density (P<.0001) than specimens from patients without metastasis. A
      significant correlation between COX-2 and tumor vascularization (r(s)=0.450,
      P=.007) as well as between COX-2 and microvessel density with VEGF expression in
      tumor tissues was found (r(s)=0.450, P=.007; r(s)=0.620, P=.0001, respectively).
      The induction of COX-2 mRNA and PGE2 synthesis by EGF and Escherichia coli
      lipopolysaccharide (LPS) in A-431 and SCC-9 cell lines, resulted in an increase
      in VEGF mRNA and protein production. Indomethacin and celecoxib reversed the EGF-
      and LPS-dependent COX-2, VEGF, and PGE2 increases. This study suggests a central
      role of COX-2 pathway in HNC angiogenesis by modulating VEGF production and
      indicates that COX-2 inhibitors may be useful in HNC treatment.

PMID- 11326317
TI  - Evidence of chromosomal instability in prostate cancer determined by spectral
      karyotyping (SKY) and interphase fish analysis.
AB  - The way in which cytogenetic aberrations develop in prostate cancer (CaP) is
      poorly understood. Spectral karyotype (SKY) analysis of CaP cell lines has shown
      that they have unstable karyotypes and also have features associated with
      chromosomal instability (CIN). To accurately determine the incidence of de novo
      structural and numerical aberrations in vitro in CaP, we performed SKY analysis
      of three independent clones derived from one representative cell line, DU145. The
      frequent generation of new chromosomal rearrangements and a wide variation in the
      number of structural aberrations within two to five passages suggested that this
      cell line exhibited some of the features associated with a CIN phenotype. To
      study numerical cell-to-cell variation, chromosome 8 aneusomy was assessed in the
      LNCaP, DU145, and PC-3 cell lines and a patient cohort of 15 CaP primary tumors
      by interphase fluorescence in situ hybridization (FISH). This analysis showed
      that a high frequency of numerical alteration affecting chromosome 8 was present
      in both in vitro and in CaP tissues. In comparison to normal controls, the
      patient cohort had a statistically significant (P<.05), greater frequency of
      cells with one and three centromere 8 copies. These data suggest that a CIN-like
      process may be contributing towards the generation of de novo numerical and
      structural chromosome abnormalities in CaP.

PMID- 11326318
TI  - Microtubule-targeting drugs induce Bcl-2 phosphorylation and association with
      Pin1.
AB  - Bcl-2 is a critical suppressor of apoptosis that is overproduced in many types of
      cancer. Phosphorylation of the Bcl-2 protein is induced on serine residues in
      tumor cells arrested by microtubule-targeting drugs (paclitaxel, vincristine,
      nocodazole) and has been associated with inactivation of antiapoptotic function
      through an unknown mechanism. Comparison of a variety of pharmacological
      inhibitors of serine/threonine-specific protein kinases demonstrated that the
      cyclin-dependent kinase inhibitor, flavopiridol, selectively blocks Bcl-2
      phosphorylation induced by antimicrotubule drugs. Bcl-2 could also be
      coimmunoprecipitated with the kinase Cdc2 in M-phase-arrested cells, suggesting
      that a Cdc2 may be responsible for phosphorylation of Bcl-2 in cells treated with
      microtubule-targeting drugs. Examination of several serine-->alanine substitution
      mutants of Bcl-2 suggested that serine 70 and serine 87 represent major sites of
      Bcl-2 phosphorylation induced in response to microtubule-targeting drugs. Both
      these serines are within sequence contexts suitable for proline-directed kinases
      such as Cdc2. Phosphorylated Bcl-2 protein was discovered to associate in M-phase
      arrested cells with Pin1, a mitotic peptidyl prolyl isomerase (PPIase) known to
      interact with substrates of Cdc2 during mitosis. In contrast, phosphorylation of
      Bcl-2 induced by microtubule-targeting drugs did not alter its ability to
      associate with Bcl-2 (homodimerization), Bax, BAG1, or other Bcl-2-binding
      proteins. Since the region in Bcl-2 containing serine 70 and serine 87 represents
      a proline-rich loop that has been associated with autorepression of its
      antiapoptotic activity, the discovery of Pin1 interactions with phosphorylated
      Bcl-2 raises the possibility that Pin1 alters the conformation of Bcl-2 and
      thereby modulates its function in cells arrested with antimicrotubule drugs.

PMID- 11326321
TI  - Restless Legs Syndrome.
AB  - Restless Legs Syndrome (RLS) is a well-defined symptom complex and is frequently
      associated with sleep disturbance and a recognized family history. It occurs
      either as idiopathic RLS or in association with many medical, neurological or
      vascular disorders. The neurological examination and routine investigations in
      idiopathic RLS are normal. Polysomnography supports the diagnosis of RLS by
      documenting the associated sleep disturbances and periodic limb movements in
      sleep (PLMS). Although MRI studies disclose no intracerebral lesions, recent
      Positron Emission Tomography (PET) and single photon emission computed tomography
      (SPECT) studies point to some involvement of the basal and red nuclei and the
      cerebellum. No definitive etiology is known for this condition, but several
      pathophysiological mechanisms have been proposed. There is supportive evidence
      that RLS is a Central Nervous System (CNS) dysfunction, suggesting widespread
      involvement of the descending dopaminergic (DA) pathways, possibly originating in
      the diencephalon or upper brainstem. This is corroborated by the successful
      treatment of RLS with DA agents, sedatives, and neurotransmitters. However, RLS
      can also occur with spinal disorders and spinal cord lesions implying the
      existence of a spinal generator. The incidence of RLS in pregnancy is well known
      and its association with vascular disorders supports another mechanism in some
      patients. The primary treatment of RLS is largely symptomatic and quite effective
      with DA agents, DA agonists, opioids and other neurotransmitters. The treatment
      of RLS associated with various diseases is aimed at the correction of the
      underlying pathological or deficiency states. Antidepressant medications
      frequently precipitate or worsen the condition of RLS.

PMID- 11326322
TI  - Risk factors for coronary heart disease in patients with spinal cord injury in
      Turkey.
AB  - OBJECTIVE: To compare the standard risk factors for coronary heart disease (CHD),
      defined in National Cholesterol Education Program II (NCEP II) of Turkish spinal
      cord injury (SCI) patients with healthy controls, discuss the results according
      to the findings in Turkish population, and SCI patients in the literature.
      DESIGN: We assessed 52 age and sex matched healthy control subjects, and 69 SCI
      patients (16 females, 53 males with the mean age of 33.9+/-11.37 years) with time
      since injury of 12.8+/-13.45 months. The study consisted of 45 paraplegics, and
      24 tetraplegics with 54% incomplete, and 46% complete injury. RESULTS: Risk
      factors for CHD according to NCEP II were; age and sex in 16%, positive family
      history in 0%, cigarette smoking in 54%, hypertension (HT) in 0%, high total
      cholesterol (TC) in 32%, high low-density lipoprotein cholesterol (LDL) in 41%,
      low high-density lipoprotein cholesterol (HDL) in 52%, and diabetes mellitus (DM)
      in 7% of our SCI patients, respectively. Compared to controls DM, high TC, LDL,
      and low HDL were statistically more frequent in SCI patients. We found a negative
      correlation between serum HDL and time since injury. TC (186+/-32 vs 205+/-36;
      P=0.025), TC/HDL (5.34+/-1.17 vs 6.26+/-1.5; P=0.005), and LDL/HDL (3.57+/-0.9 vs
      4.16+/-1.3; P=0.027) were significantly increased in patients with time since
      injury of more than 1 year, while HDL levels (35.8+/-6.36 vs 33.86+/-6.47;
      P=0.213) decreased without reaching statistical significance. The lipid profiles
      did not show any correlation with the neurological level, and completeness of
      lesions. CONCLUSIONS: SCI confers additional CHD risk over that present
      inherently in the parent population due to enforced sedentary lifestyle and this
      increases with time since injury. The preliminary study consisting of 26 patients
      was accepted for poster presentation in Copenhagen, Denmark (18-20 June 1999) at
      the 38th Annual Scientific Meeting of IMSOP in association with the Nordic
      Medical Society of Paraplegia.

PMID- 11326319
TI  - Coregulation of glucose uptake and vascular endothelial growth factor (VEGF) in
      two small-cell lung cancer (SCLC) sublines in vivo and in vitro.
AB  - We examined the relationship between (18)F- labeled 2-fluro-2-deoxy-d-glucose
      (FDG) uptake, and expression of glucose transporters (GLUTs) in two human small
      cell lung cancer (SCLC) lines CPH 54A and CPH 54B. Changes in the expression of
      GLUTs and vascular endothelial growth factor (VEGF) during 12-, 18-, and 24 hours
      of severe hypoxia in vivo (xenografts) and in vitro (cell cultures) were recorded
      for both tumor lines. The two SCLC lines are subpopulations of the same patient
      tumor. In spite of their common genomic origin they represent consistently
      different metabolic and microenvironmental phenotypes as well as treatment
      sensitivities. There were higher levels of Glut-1 protein in 54B and a
      correspondingly higher FDG uptake in this tumor line (P<.001). During hypoxia a
      significant upregulation of in VEGF mRNA, GLUT-1 mRNA, and Glut-1 and -3 protein
      occurred with a distinctly different time course in the two cell lines. A similar
      co-upregulation of GLUT and VEGF was seen in hypoxic tumors of both lines. There
      were no significant changes of HIF-1alpha mRNA during hypoxia in either of the
      cell lines. A more detailed understanding of such correlations between glucose
      metabolism, angiogenesis, and microenvironmental phenotype of tumors, by positron
      emission tomography (PET) and molecular techniques might further sophisticate our
      interpretation of glycolytic predominance in tumors as seen by 18FFDG PET.

PMID- 11326323
TI  - Vital capacity in tetraplegics twenty years and beyond.
AB  - OBJECTIVES: To observe the trends in vital capacity (VC) over time in
      tetraplegics 20 years and more after injury, the effects of age at injury,
      severity of injury and gender on this trend. METHODS: The medical records of all
      spinal cord injured persons admitted to a regional spinal injury center from
      January 1960 to December 1996 were reviewed. Fifty-seven patients had documented
      post-rehabilitation VC (mean 1.3+/-1.1 years) and VC at 10 (mean 11.8+/-2.69) and
      20 (20.60+/-2.67) years post injury and beyond. RESULTS: The mean age at injury
      was 23.2+/-9.1 years. Severity of injury when classified according the system
      proposed by Coll et al were: Group 1: C1-4 Frankel A injury: 11.6%, Group 2: C5-8
      Frankel A injury: 55.6%, Group 3: C2-8 Frankel B and C: 29.8% and Group 4: C2-8
      Frankel D: 3.5% respectively. The mean VC at initial, 10 and 20 years post injury
      was 2586+/-948, 2803+/-940 and 2525+/-818 cc respectively. Multivariate analysis
      of variance revealed that there was significant difference in VC over a 20 year
      period, (F(2,54)=8.43, P<0.05). The difference between VC at 10 years and VC at
      20 years accounted for the 19.8% of the variance in VC over time (F(1,55)=12.35,
      P<0.05). Age at injury, gender and severity of injury did not have a significant
      influence on the rate of decline in VC. Analysis of a subset of 26 patients who
      were followed up more than 20 years post injury (range 22 to 34.5 years) revealed
      similar, with a greater drop in the VC from 10 years post injury (F(1,23)=6.52,
      P<0.05). In this subset of patients, the mean VC at initial injury was 2840.9+/
      847.3 cc, at 10 years was 2549.6+/-750.3 cc, at 20 years was 2400.9+/-724.1 cc
      and beyond 20 years was 2194.2+/-738.7 cc. There was no significant difference in
      mean VC between non smokers and ex/current smokers at initial, 10 and 20 years
      post injury, using the independent t-test (P>0.05). CONCLUSION: Vital capacity in
      tetraplegics declines significantly over the years, with a greater decline
      occurring at more than 20 years post injury.

PMID- 11326324
TI  - Results from bone mineral density scans in twenty-two complete lesion
      paraplegics.
AB  - STUDY DESIGN: The bone mineral density (BMD) in 22 male subjects with complete
      lesion paraplegia sustained 1.8 to 27 years previously was measured. The
      measurements were used in screening each subject for a research programme
      investigating the restoration of standing using functional electrical stimulation
      (FES). OBJECTIVES: To assess the extent of bone loss in this group of subjects
      and correlation to age, time post-injury and level of lesion. SETTING: District
      General Hospital in the UK. METHODS: BMD was measured by dual energy X-ray
      absorptiometry (DEXA) in the lumbar spine and femoral neck and expressed as an
      indirect index to an age matched 'normal' population. Fracture risk was described
      from this score using published data indicating that the risk increased with each
      standard deviation difference from the 'normal' mean. RESULTS: The bone density
      in the lumbar spine was better preserved than in the femoral neck. BMD in the
      lumbar spine was found to be greater than the mean from the age matched
      population in 57.1% of subjects. Bone loss at the femoral neck suggested that
      81.8% of the subjects were at increased risk of fracture, but only 22.7% were at
      a high risk. No correlation was found between BMD at the lumbar spine or the
      femoral neck and age, lesion level or time post-injury. CONCLUSION: The study
      indicates that further investigation into baseline BMD values for the SCI
      population is required to improve information provided to patients and assessment
      of fracture risk on an individual basis.

PMID- 11326325
TI  - Thermoregulatory responses to repeated warm water immersion in subjects who are
      paraplegic.
AB  - OBJECTIVE: To compare thermoregulatory responses to repeated warm water immersion
      (39 degrees C) between physically active subjects who are paraplegic or able
      bodied in order to gain insight into rehabilitative and adaptive processes.
      METHODS: Five paraplegic (P) and six able-bodied (AB) males participated. VO2
      peak was determined by open-circuit spirometry using a cycle ergometer (AB) and
      propelling a wheelchair on a motor driven treadmill (P). Subjects sat immersed to
      the nipple line in 39 degrees C water for 60 min for 5 consecutive days. Pre- and
      post-test measurements included heart rate (HR), oesophageal temperature (Tes),
      sweat onset and rate (dew point hygrometry). Venous blood was obtained before,
      and during immersion to estimate changes in plasma volume. RESULTS: The P group
      was older and lighter than AB group (P<0.05). VO2max, VCO2max and VE(max) were
      significantly greater in AB group. HR at rest and after 60 min immersion was not
      significantly different between the groups pre- or post-test. Tes significantly
      increased after 60 min immersion in both groups, at both pre- and post-testing
      sessions. Post-test Tes after 60 min immersion (AB) was significantly less than
      Tes after 60 min of immersion pre-test. The DeltaTes (Tes 60 min-Tes 0 min) was
      significantly higher in AB group than the P group at pre- but not post-testing.
      No significant changes in sweat onset or rate were found for the AB or P groups
      during the pre- or post testing sessions. Significant expansion of plasma volume
      occurred during immersion in both groups, pre- and post-immersion sessions.
      CONCLUSIONS: Repeated warm water immersion (39 degrees C) for 60 min per day for
      a total of 5 days did not produce a significant adaptive response in P group. In
      the AB group, Tes at the end of 60 min immersion was significantly lower after
      the adaptation period.

PMID- 11326326
TI  - Pattern of use and user satisfaction of Neuro Control Freehand system.
AB  - OBJECTIVES: Evaluation of the use and acceptability of the Neuro Control Freehand
      system. STUDY DESIGN: A questionnaire was sent in a single mail shot to users of
      the system. Administration was by a 3rd party with anonymous returns. SETTING: A
      supra regional spinal unit in the UK. METHODS: The Freehand system is an
      implanted Functional Electrical Stimulation (FES) device for restoration of
      lateral and palmar grasps following C5 or C6 tetraplegia. RESULTS: Replies were
      received from seven users of the system who had an average experience of 23
      months use. All used the system daily and had increased their range of activities
      of daily living skills. Some problems had been experienced with equipment
      reliability and skin allergy to the tape used to secure external components. Six
      users felt more confident when using the system and seven felt their quality of
      life had improved. CONCLUSION: The Freehand system provides increased function
      that is considered by its users to be of benefit.

PMID- 11326327
TI  - Reproducibility and validity of a questionnaire filled in by spinal cord lesioned
      individuals before regular follow-up.
AB  - OBJECTIVE: To speed up and focus (biennial) check-ups of out-patients with spinal
      cord lesions by means of a brief mail questionnaire concerning specific
      impairments as well as general life conditions. METHOD: A trial 69-item
      questionnaire was filled in twice, at home and on arrival for check-up, and, for
      a third time, by the physician during the consultation. Out of 115 check-ups, 107
      and 105 could be included in a reproducibility and validity assessment
      respectively. RESULTS: Excellent agreement between the first two completions
      ('reproducibility') and between the markings made at home and those made by the
      physician ('validity') was obtained for the majority of the items. Those items
      not performing satisfactorily, not least those relating to defecation, were
      scrutinised. CONCLUSION: After revision, the questionnaire can serve the above
      mentioned purposes in a cost-effective and clinically satisfying manner. Further
      benefits are envisaged by computerised longitudinal monitoring of the patients'
      answers. Finally, we have pointed towards weak items/questions in our
      questionnaire, and we hope this can be of help to others who want to use similar
      questionnaires in their daily practice.

PMID- 11326328
TI  - Treatment of male infertility due to spinal cord injury using rectal probe
      electroejaculation: the Israeli experience.
AB  - STUDY DESIGN: Male infertility caused by anejaculation is common among patients
      with spinal cord injury (SCIP). The fertility options for SCIP have improved
      impressively over the past 10 years. We present the Israeli experience in the
      treatment of infertility in a large series of SCIP. The issues which are
      addressed include the treatment of ejaculatory dysfunction, seminal quality and
      fertility management in SCIP. SETTING: Sexual rehabilitation clinic, Neuro
      Rehabilitation department, Sheba Medical Center, Israel. METHODS: Between June
      1992 and May 1998, a total of 84 consecutive SCIP were treated in our clinic with
      electro-ejaculation (EEJ), representing a sample of the SCIP population, composed
      mostly of young men traumatically injured. The patients have sustained different
      levels and completeness of spinal injury. Among the patients 33 were interested
      in achieving pregnancy (39.3%), while the rest were interested in determining
      fertility potential for family. With EEJ, a low-current stimulation of the
      ejaculatory organs via a rectal probe is done. The collected semen is used for
      fertility determination or for fertilization. RESULTS: Eighty-four patients were
      treated by EEJ. Mean age was 31.3 and mean age at injury was 21.7. There were 29
      cervical, 50 thoracic and five lumbar lesions. Sixty-three had complete injury
      (ASIA A) and 21 incomplete (ASIA B -15, ASIC C -5, ASIA D -1). Fifty-nine had
      upper motor neuron lesions, and 25 had lower motor neuron. A total of 355
      stimulations were performed. Ejaculate was obtained in all patients in 350
      stimulations (98.6%), and sperm was present in 74 patients (88.1%) in 296 of the
      stimulations (83.4%). Fairly good numbers of spermatozoa were obtained, whereas
      sperm motility and morphology of spermatozoa were low in most cases. A
      significant difference in sperm count, motility and morphology was noted between
      antegrade and retrograde samples. No significant improvement in sperm quality
      after four repeated consecutive stimulations was noted in 38 SCIP. Side effects
      were minor and encountered in 16 patients (19.1%). Out of 33 couples who wished
      to achieve pregnancy, 26 reached the stage of insemination. Four pregnancies were
      achieved after 33 cycles of In-Uterine-Insemination (pregnancy rate 28.6% per
      couple), and 15 after 68 cycles of In-Vitro-Fertilization (micromanipulation)
      (pregnancy rate of 68.75% per couple). In all, of 101 conception attempts 23 were
      successful, resulting in pregnancies in 18 couples, and accounting for an overall
      pregnancy rate of 70% per couple. CONCLUSION: The high percentage of pregnancies
      imply that, despite the typically poor sperm motility noted in EEJ, rectal probe
      EEJ combined with assisted reproductive techniques, and performed by a team
      approach, is an efficient and safe technique for treating infertility among SCIP.

PMID- 11326329
TI  - History of post-traumatic syringomyelia: post traumatic syringomyelia prior to
      1920.
AB  - STUDY DESIGN: Review of five cases of post-traumatic syringomyelia originally
      described between 1898-1920. OBJECTIVES: To describe the earliest presentation of
      post-traumatic syringomyelia and to compare to modern day views of this
      condition. SETTING: Historical review. RESULTS: Pathogenesis and interpretation
      of the findings are discussed in the light of current knowledge. CONCLUSION:
      Credit for the first description of post-traumatic syringomyelia (in 1898) should
      go to W Wagner and P Stolper.

PMID- 11326330
TI  - Generalised spinal cord atrophy, Chiari-I malformation, and syringomyelia.
AB  - OBJECTIVES: To report the simultaneous occurrence of generalised spinal cord
      atrophy, Chiari-I malformation, and syringomyelia. SETTING: Vienna, Austria. CASE
      DESCRIPTION: An 83-year old woman presented with predominantly lower limb and
      distal tetraparesis, diffuse wasting, spasticity of both lower limbs,
      contractures, and severe kyphoscoliosis. Radiographic examinations revealed
      generalised spinal cord atrophy, Chiari-I malformation, and syringomyelia between
      C5 and C7. The generalised spinal cord atrophy was assumed to be due to either
      secondary atrophy or spontaneous collapse of a formerly more extensive
      syringomyelia. All other causes for generalised spinal cord atrophy were
      excluded. CONCLUSIONS: Generalised spinal cord atrophy in a patient with Chiari-I
      malformation and syringomyelia may be due to either secondary atrophy or
      spontaneous collapse of a formerly holocord syringomyelia. Myelography and MRI
      imaging of the spine are helpful in diagnosing this condition.

PMID- 11326331
TI  - Massive distension of urinary bladder in a patient with cervical spinal cord
      injury who was treated initially in a general hospital.

PMID- 11326334
TI  - X-linked creatine-transporter gene (SLC6A8) defect: a new creatine-deficiency
      syndrome.
AB  - We report the first X-linked creatine-deficiency syndrome caused by a defective
      creatine transporter. The male index patient presented with developmental delay
      and hypotonia. Proton magnetic-resonance spectroscopy of his brain revealed
      absence of the creatine signal. However, creatine in urine and plasma was
      increased, and guanidinoacetate levels were normal. In three female relatives of
      the index patient, mild biochemical abnormalities and learning disabilities were
      present, to various extents. Fibroblasts from the index patient contained a
      hemizygous nonsense mutation in the gene SLC6A8 and were defective in creatine
      uptake. The three female relatives were heterozygous for this mutation in SLC6A8,
      which has been mapped to Xq28.

PMID- 11326333
TI  - A recurrent RNA-splicing mutation in the SEDL gene causes X-linked
      spondyloepiphyseal dysplasia tarda.
AB  - Spondyloepiphyseal dysplasia tarda (SEDL) is a genetically heterogeneous disorder
      characterized by mild-to-moderate short stature and early-onset osteoarthritis.
      Both autosomal and X-linked forms have been described. Elsewhere, we have
      reported the identification of the gene for the X-linked recessive form, which
      maps to Xp22.2. We now report characterization of an exon-skipping mutation
      (IVS3+5G-->A at the intron 3 splice-donor site) in two unrelated families with
      SEDL. Using reverse transcriptase (RT)-PCR, we demonstrated that the mutation
      resulted in elimination of the first 31 codons of the open reading frame. The
      mutation was not detected in 120 control X chromosomes. Articular cartilage from
      an adult who had SEDL and carried this mutation contained chondrocytes with
      abundant Golgi complexes and dilated rough endoplasmic reticulum (ER). RT-PCR
      experiments using mouse/human cell hybrids revealed that the SEDL gene escapes X
      inactivation. Homologues of the SEDL gene include a transcribed retropseudogene
      on chromosome 19, as well as expressed genes in mouse, rat, Drosophila
      melanogaster Caenorhabditis elegans, and Saccharomyces cerevisiae. The latter
      homologue, p20, has a putative role in vesicular transport from ER to Golgi
      complex. These data suggest that SEDL mutations may perturb an intracellular
      pathway that is important for cartilage homeostasis.

PMID- 11326335
TI  - Benign familial infantile convulsions: mapping of a novel locus on chromosome
      2q24 and evidence for genetic heterogeneity.
AB  - In 1997, a locus for benign familial infantile convulsions (BFIC) was mapped to
      chromosome 19q. Further data suggested that this locus is not involved in all
      families with BFIC. In the present report, we studied eight Italian families and
      mapped a novel BFIC locus within a 0.7-cM interval of chromosome 2q24, between
      markers D2S399 and D2S2330. A maximum multipoint HLOD score of 6.29 was obtained
      under the hypothesis of genetic heterogeneity. Furthermore, the clustering of
      chromosome 2q24-linked families in southern Italy may indicate a recent founder
      effect. In our series, 40% of the families are linked to neither chromosome 19q
      or 2q loci, suggesting that at least three loci are involved in BFIC. This
      finding is consistent with other autosomal dominant idiopathic epilepsies in
      which different genes were found to be implicated.

PMID- 11326336
TI  - Dominant inheritance of sialuria, an inborn error of feedback inhibition.
AB  - "French type" sialuria, a presumably dominant disorder that, until now, had been
      documented in only five patients, manifests with mildly coarse facies, slight
      motor delay, and urinary excretion of large quantities (>1 g/d) of free N
      acetylneuraminic acid (NeuAc). The basic defect consists of the very rare
      occurrence of failed feedback inhibition of a rate-limiting enzyme, in this case
      uridinediphosphate-N-acetylglucosamine (UDP-GlcNAc) 2-epimerase, by a downstream
      product, in this case cytidine monophosphate (CMP)-NeuAc. We report a new patient
      with sialuria who has a heterozygous G-->A substitution in nucleotide 848 of the
      epimerase gene, which results in an R266Q change. The proband's other allele, as
      expected, had no mutation. However, the heterozygous R266Q mutation was detected
      in the patient's mother, who has similarly increased urinary levels of free
      NeuAc, thereby confirming, for the first time, the dominant mode of inheritance
      of this inborn error. The biochemical diagnosis of the proband was verified by
      the greatly increased level of free NeuAc in his cultured fibroblasts, the NeuAc
      distribution, mainly (59%) in the cytoplasm, and by the complete failure of 100
      microM CMP-NeuAc to inhibit UDP-GlcNAc 2-epimerase activity in the mutant cells.
      These findings call for expansion of the phenotype to include adults and for more
      extensive assaying of free NeuAc in the urine of children with mild developmental
      delay. The prevalence of sialuria is probably grossly underestimated.

PMID- 11326337
TI  - Missense mutations in the N-terminal domain of human phenylalanine hydroxylase
      interfere with binding of regulatory phenylalanine.
AB  - Hyperphenylalaninemia due to a deficiency of phenylalanine hydroxylase (PAH) is
      an autosomal recessive disorder caused by >400 mutations in the PAH gene. Recent
      work has suggested that the majority of PAH missense mutations impair enzyme
      activity by causing increased protein instability and aggregation. In this study,
      we describe an alternative mechanism by which some PAH mutations may render PAH
      defective. Database searches were used to identify regions in the N-terminal
      domain of PAH with homology to the regulatory domain of prephenate dehydratase
      (PDH), the rate-limiting enzyme in the bacterial phenylalanine biosynthesis
      pathway. Naturally occurring N-terminal PAH mutations are distributed in a
      nonrandom pattern and cluster within residues 46-48 (GAL) and 65-69 (IESRP), two
      motifs highly conserved in PDH. To examine whether N-terminal PAH mutations
      affect the ability of PAH to bind phenylalanine at the regulatory domain, wild
      type and five mutant (G46S, A47V, T63P/H64N, I65T, and R68S) forms of the N
      terminal domain (residues 2-120) of human PAH were expressed as fusion proteins
      in Escherichia coli. Binding studies showed that the wild-type form of this
      domain specifically binds phenylalanine, whereas all mutations abolished or
      significantly reduced this phenylalanine-binding capacity. Our data suggest that
      impairment of phenylalanine-mediated activation of PAH may be an important
      disease-causing mechanism of some N-terminal PAH mutations, which may explain
      some well-documented genotype-phenotype discrepancies in PAH deficiency.

PMID- 11326339
TI  - Pressure support noninvasive positive pressure ventilation treatment of acute
      cardiogenic pulmonary edema.
AB  - We assessed cardiogenic pulmonary edema (CPE) patient response to full mask
      pressure support noninvasive positive pressure ventilation (NPPV). Adult patients
      presenting to the emergency department (ED) in acute respiratory failure who
      clinically required endotracheal intubation (ETI) were studied. In addition to
      routine therapy consisting of oxygen, nitrates, and diuretics, patients were
      started on full mask NPPV using a Puritan Bennett 7200 ventilator delivering
      pressure support 10 cm H(2)O, PEEP 5 cm H(2)O, FiO(2) 100%. Pressure support was
      titrated to achieve tidal volumes of 5 to 7 mL/kg, and PEEP titrated to achieve
      oxygen saturation (SaO(2)) > 90%. Outcome measures included arterial blood gas
      (ABG), Borg dyspnea score, vital signs, and need for ETI. Twenty patients mean
      age 74.7 +/- 14.3 years were entered on the study. Initial mean values on FiO(2)
      100% by nonrebreather mask: pH 7.17 +/-.13, paCO(2) 65.5 +/- 19.4 mmHg, paO(2)
      73.8 +/- 27.3 mm Hg, SaO(2) 89.7 +/- 10.0%, Borg score 8.1 +/- 1.4, and
      respiratory rate(RR) 38 +/- 6.3. At 60 minutes of NPPV, improvement was
      statistically significant: pH 7.28 (difference.11; 95% CI.04-.19), paCO(2) 45
      (difference 20.5; 95% CI 8-33), Borg score 4.1 (difference 4.0; 95% CI 3-5), and
      RR 28.2 (difference 9.8; 95% CI 5-14). NPPV duration ranged from 30 minutes to 36
      hours (median 2 hours, 45 minutes). Eighteen patients (90%) improved allowing
      cessation of NPPV. Two patients with concomitant severe chronic obstructive
      pulmonary disease (COPD) required ETI. There were no complications of NPPV. NPPV
      using full face mask and pressure support provided by a conventional volume
      ventilator is an effective treatment for CPE and may help prevent ETI.

PMID- 11326338
TI  - Autosomal dominant craniometaphyseal dysplasia is caused by mutations in the
      transmembrane protein ANK.
AB  - Craniometaphyseal dysplasia (CMD) is a rare skeletal disorder characterized by
      progressive thickening and increased mineral density of craniofacial bones and
      abnormally developed metaphyses in long bones. Linkage studies mapped the locus
      for the autosomal dominant form of CMD to an approximately 5-cM interval on
      chromosome 5p, which is defined by recombinations between loci D5S810 and
      D5S1954. Mutational analysis of positional candidate genes was performed, and we
      describe herein three different mutations, in five different families and in
      isolated cases, in ANK, a multipass transmembrane protein involved in the
      transport of intracellular pyrophosphate into extracellular matrix. The mutations
      are two in-frame deletions and one in-frame insertion caused by a splicing
      defect. All mutations cluster within seven amino acids in one of the six possible
      cytosolic domains of ANK. These results suggest that the mutated protein has a
      dominant negative effect on the function of ANK, since reduced levels of
      pyrophosphate in bone matrix are known to increase mineralization.

PMID- 11326340
TI  - Six-hour versus 12-hour protocols for AMI: CK-MB in conjunction with myoglobin.
AB  - The objective was to test the hypothesis that a protocol using myoglobin and
      creatine kinase-MB (CK-MB) can rapidly and safely exclude myocardial infarction
      (MI). The study used a prospective, convenience cohort of ED patients with
      clinically suspected myocardial ischemia. Myoglobin was measured on presentation,
      2 and 6 hours later; CK-MB was measured on presentation, 6, 12, and 18 hours
      later. Of 519 patients, 76 (15%) had MIs, all of whom "ruled in" within 12 hours
      using a combination of myoglobin and CK-MB, for a sensitivity of 100% (95% CI,
      95% to 100%), specificity of 92% (95% CI, 89% to 94%), LR (+) of 12 (95% CI, 9 to
      16), and an LR (-) of 0.03 (95% CI, 0.0 to 0.05). Of the 76 patients with MIs, 73
      ruled in with a 6 hour protocol, also using a combination of CK-MB and myoglobin,
      for a sensitivity of 96% (95% CI, 89% to 99%), specificity of 92% (95% CI, 89% to
      94%), LR (+) of 11 (95% CI, 8 to 16), and an LR (-) of 0.04 (95% CI, 0.01 to
      0.12). Our results support the hypothesis that, using an abbreviated protocol
      with CK-MB and myoglobin, MI can be reliably ruled out in ED patients with
      suspected ischemia.

PMID- 11326341
TI  - Factors associated with sudden death of individuals requiring restraint for
      excited delirium.
AB  - The purpose of this article is to identify and rank factors associated with
      sudden death of individuals requiring restraint for excited delirium. Eighteen
      cases of such deaths witnessed by emergency medical service (EMS) personnel are
      reported. The 18 cases reported were restrained with the wrists and ankles bound
      and attached behind the back. This restraint technique was also used for all 196
      surviving excited delirium victims encountered during the study period. Unique to
      these data is a description of the initial cardiopulmonary arrest rhythm in 72%
      of the sudden death cases. Associated with all sudden death cases was struggle by
      the victim with forced restraint and cessation of struggling with labored or
      agonal breathing immediately before cardiopulmonary arrest. Also associated was
      stimulant drug use (78%), chronic disease (56%), and obesity (56%). The primary
      cardiac arrest rhythm of ventricular tachycardia was found in 1 of 13 victims
      with confirmed initial cardiac rhythms, with none found in ventricular
      fibrillation. Our findings indicate that unexpected sudden death when excited
      delirium victims are restrained in the out-of-hospital setting is not infrequent
      and can be associated with multiple predictable but usually uncontrollable
      factors.

PMID- 11326342
TI  - The demographics of e-mail for emergency medicine research.
AB  - Escalating costs of research combined with increasing use of e-mail by emergency
      physicians (EP), justifies studying whether electronic surveying (ES) is a valid
      methodology for research. Our primary study object is to delineate the
      demographics of EP with e-mail. Secondary objectives are to ascertain ES response
      rates and to identify response bias between "individual" versus "bulk" e
      mailings. The 1999 American College of Emergency Physicians Membership Guide
      identified a pool of e-mail addresses. Of the 1,752 EP surveyed, 1,386 (79%) had
      valid e-mail addresses and 574 responded. A response rate of 41% questions the
      validity of ES for research. Demographic data of EP regarding mean age (38.2
      years); gender (82.4% men); title (86.8% MD); practice (87% ED); practice
      location (49.6% urban); training (56% EM residency); research participation
      (65.5%); screening e-mail (7%); is representative of EP overall. Finally,
      comparison of individual versus bulk e-mail to survey participants showed a 13.6%
      (5.5-21.7; 95% CI) improvement in overall response.

PMID- 11326343
TI  - The utility of routine electrolytes and blood cell counts in patients with chest
      pain.
AB  - The objective of the study was to determine whether the routine screening
      laboratory tests, electrolytes (E) and hemoglobin and hematocrits (H/H), could
      have been safely avoided in ED patients presenting with chest pain. Retrospective
      case series over a 3-month period were reviewed. Acceptable indications for E and
      H/H test ordering were prospectively developed using American College of
      Emergency Physicians (ACEP) guidelines. Charts were reviewed to determine whether
      any indications were present, whether the E and H/H laboratory tests were
      abnormal, and whether the abnormal test affected treatment or disposition.
      Patients were excluded if they had an abnormal electrocardiogram (ECG) indicating
      ischemia or electrolyte abnormality. This resulted in 191 patients meeting
      inclusion criteria. Sixty-eight patients did not have any criteria for ordering E
      or H/H. Of these, only one (1.5%) had an abnormal laboratory test. The
      sensitivity of the guidelines for predicting an abnormal laboratory test was 96%
      (95 CI, 82 to 100%) and the specificity was 46% (95CI, 38 to 54%). There were no
      interventions, consultations, or any change in disposition based on E or H/H
      testing in these patients. Of the 123 patients that met at least one criteria for
      ordering laboratory tests, 27 (18%) had an abnormal result. It was concluded that
      practice guidelines may reduce the number of E and H/H tests ordered without
      missing significant abnormalities. A prospective trial is needed to validate
      these findings.

PMID- 11326344
TI  - Is appendiceal CT scan overused for evaluating patients with right lower quadrant
      pain?
AB  - Reports citing excellent sensitivity, specificity, and predictive accuracy of
      focused appendiceal computed tomography (CT) and showing an overall reduction in
      resource use and nontherapeutic laparotomies have led to increasing use of that
      imaging modality. Diagnostic algorithms have begun to incorporate appendiceal CT
      for patients presenting to the emergency department with right lower quadrant
      pain. We present a series of 4 cases in which use of appendiceal CT ultimately
      led to increased cost, resource use, and complexity in patient care. The results
      of these cases support an argument against unbridled use of appendiceal CT
      scanning and reinforce the need for clinical evaluation by the operating surgeon
      before routine performance of appendiceal CT scan.

PMID- 11326345
TI  - GPS computer navigators to shorten EMS response and transport times.
AB  - GPS (global positioning satellite system to determine one's position on earth)
      units have become inexpensive and compact. The purpose of this study is to assess
      the effectiveness of a GPS enhanced computer street map navigator to improve the
      ability of EMS drivers in an urban setting to locate their destination and
      shorten response times. For part I, residential addresses in the city were
      randomly selected from a telephone directory. Two driver/navigator teams were
      assigned to drive to the address adhering to speed limits. One team used a
      standard street map, whereas the other team used a GPS computer navigator. The
      travel time and distance of the runs were compared. For part II, the computer GPS
      navigator was placed on an ambulance to supplement their normal methods of
      navigation to find the address requesting EMS. After the run was completed, EMS
      providers were interviewed to determine their opinion of whether the GPS
      navigator was helpful. For part I the results showed that in the 29 initial test
      runs, comparing the GPS team versus the standard map team, the mean distances
      traveled were 8.7 versus 9.0 kilometers (not significant) and the mean travel
      times were 13.5 versus 14.6 minutes (P=.02), respectively. The GPS team arrived
      faster in 72% runs. For part II the results showed that most EMS providers
      surveyed noted that the GPS computer navigator enhanced their ability to find the
      destination and all EMS providers acknowledged that it would enhance their
      ability to find a destination in an area in which they were unfamiliar. These
      results suggest that a portable GPS computer navigator system is helpful and can
      enhance the ability of prehospital care providers to locate their destination.
      Because these units are accurate and inexpensive, GPS computer navigators may be
      a valuable tool in reducing pre-hospital transport times.

PMID- 11326346
TI  - Lidocaine inhalation for cough suppression.
AB  - The purpose of this study was to observe the effectiveness of lidocaine in
      suppressing cough which is a logical extension of its established use in
      bronchoscopy. Nebulized lidocaine, preceded by standard nebulized albuterol
      inhalation driven by oxygen was given to suppress cough in a selected group of
      patients with intractable cough severe enough to disrupt daily life activities,
      especially sleep. Patients included those with asthma, reactive airways disease,
      and chronic obstructive pulmonary disease (COPD). In these selected patients,
      nebulized lidocaine was very effective in suppressing cough, and thus buying time
      for more definitive therapies to work. This observation merits further study and
      confirmation for the benefit of patients.(Am J Emerg Med 2001;19:206-207.

PMID- 11326347
TI  - NPB-75: A portable quantitative microstream capnometer.
AB  - A portable quantitative microstream capnometer (NPB-75) was tested in intubated
      children. The end-tidal CO(2) values measured by this device showed good
      agreement with concomitantly measured values of a stationary mainstream
      capnometer (N-6000). This lightweight device, with a 4-hour battery life, graphic
      capnogram display, and audiovisual alarms is well suited for the prehospital
      setting.

PMID- 11326348
TI  - Emphysematous cystitis: a radiographic diagnosis.
AB  - Emphysematous cystitis is a somewhat uncommon entity in which early diagnosis and
      treatment play a key role in avoiding potentially high morbidity and mortality.
      An elderly woman with emphysematous cystitis and no comorbid factors, except
      advanced age, is presented. This case illustrates the key features in the
      radiographic diagnosis of this unusual disease. Discussion of the cause,
      diagnosis, and treatment of emphysematous cystitis emphasizes prompt recognition,
      drainage of the bladder and use of appropriate broad spectrum antibiotic therapy.

PMID- 11326349
TI  - 2:1 Atrioventricular block: order from chaos.
AB  - 2:1 AV block can occur in either the AV node or the His-Purkinje system and
      cannot be classified into type I or type II second-degree AV block because there
      is only one PR interval to examine before the blocked P wave. It is inappropriate
      to use terms such as 2:1 or 3:1 type I or type II AV block because this
      characterization violates the accepted traditional definitions of type I and type
      II block based on electrocardiographic patterns and not on the anatomical site of
      block. Type I and type II second-degree AV block can progress to 2:1 AV block,
      and 2:1 AV block can regress to type I or type II block. Consequently, the site
      of the lesion in 2:1 block can often be determined by seeking the company 2:1 AV
      block keeps. An association with type I block and a narrow QRS complex almost
      always reflects AV nodal block but type I block with a wide QRS complex occurs
      more commonly in the His-Purkinje system than the AV node. Type II block, if
      correctly defined, is always infranodal. Outside of acute myocardial infarction,
      sustained 2:1 and 3:1 AV block with a wide QRS complex occurs in the His-Purkinje
      system in 80% of cases and 20% in the AV node. Administration of atropine in
      patients with His-Purkinje disease may increase the degree of AV block.

PMID- 11326350
TI  - Atrioventricular dissociation.
AB  - Atrioventricular (AV) dissociation is an electrocardiographic syndrome; a
      descriptive term for a variety of conditions of abnormal cardiac conduction which
      all feature independent function of the atria and ventricles. AV dissociation can
      be subclassified as AV dissociation by default (an independent ventricular
      pacemaker responds to slowing of the dominant atrial pacemaker) versus AV
      dissociation by usurpation (acceleration of a latent pacemaker takes control of
      cardiac conduction by exceeding the intrinsic atrial rate). Inclusion of third
      degree AV block (complete heart block) as a manifestation of AV dissociation is
      controversial, yet is functionally appealing in that this disorder also features
      independent activity of the atria and ventricles.

PMID- 11326351
TI  - Acute dyspnea in a woman with swelling of the left leg treated with low molecular
      weight heparine.
AB  - A case of rectus sheath hematoma diagnosed initially as probable pulmonary
      embolism in a patient on anticoagulation with low molecular weight heparins for
      swelling of the left leg is presented. Prompt consideration of this hematoma in
      the emergency department is important to avoid unnecessary and potentially
      dangerous treatment.

PMID- 11326352
TI  - Orthopedic pitfalls in the ED: Galeazzi and Monteggia fracture-dislocation.
AB  - Occult dislocations at the wrist and elbow frequently accompany forearm
      fractures. When left unrecognized and untreated, these injuries lead to a high
      incidence of long-term functional disability and chronic pain. Emergency medicine
      practitioners need to be vigilant for both Galeazzi (distal radius fracture with
      radioulnar joint disruption), and Monteggia (proximal ulna fracture with radial
      head dislocation) fracture-dislocations. This review article examines the
      clinical presentation, diagnostic techniques, and management options applicable
      to the emergency practitioner.

PMID- 11326353
TI  - Periaortic contrast medium extravasation on chest CT in traumatic aortic injury:
      a sign for immediate thoracotomy.
AB  - Traumatic aortic injury (TAI) after blunt chest trauma is potentially a lethal
      condition. The injury must be diagnosed promptly and accurately. Evaluation for
      traumatic aortic injury begins with an assessment of mechanism of injury, a
      physical examination and chest radiography. In recent years, chest computed
      tomography (CT) has been advocated as a better screening tool to detect TAI but
      there is still controversial over the confirmatory diagnostic value of CT. For
      hemodynamically unstable patients in whom chest CT had shown direct sign of
      aortic injury and with periaortic contrast medium extravasation, we advocate that
      these patients should be operated on immediately without aortogram to avoid
      unnecessary delay. Herein, we describe a case of TAI with direct signs and
      periaortic contrast extravasation and discuss if chest CT can substitute an
      aortogram as a diagnostic tool when direct signs of TAI are revealed.

PMID- 11326354
TI  - Diving medicine: contemporary topics and their controversies.
AB  - SCUBA diving is a popular recreational sport. Although serious injuries occur
      infrequently, when they do knowledge of diving medicine and/or where to obtain
      appropriate consultation is essential. The emergency physician is likely to be
      the first physician contact the injured diver has. We discuss 8 subjects in
      diving medicine which are contemporary, yet may have controversies associated
      with them. From this information the physician dealing primarily with the injured
      diver will have a basis for understanding and managing, as well as where to find
      additional help, for his/her patients' diving injuries.

PMID- 11326355
TI  - A fibrinogenemia presenting as acute left upper quadrant pain in a 16-year-old
      boy.

PMID- 11326356
TI  - Foreign body reactions to dermabond.

PMID- 11326357
TI  - Normal cremasteric reflex in a case of testicular torsion.

PMID- 11326358
TI  - Benign pneumoperitoneum and pneumatosis intestinalis.

PMID- 11326359
TI  - Acute abdominal pain in an elderly woman.

PMID- 11326360
TI  - Full reversal of hypercapnic coma by noninvasive positive pressure ventilation.

PMID- 11326362
TI  - Instant telemedicine ECG consultation with cardiologists using pocket wireless
      computers.

PMID- 11326361
TI  - Amiodarone-induced long QT and polymorphic ventricular tachycardia.

PMID- 11326363
TI  - ED follow-up: A comparison of admission and discharge diagnoses.

PMID- 11326364
TI  - Assuring the quality of office-based surgery.

PMID- 11326365
TI  - Diagnosis and treatment of strictures and kinks in salivary gland ducts.
AB  - PURPOSE: This article describes the use of sialoendoscopy for diagnosis and
      treatment of strictures and kinks in the major salivary glands ducts. PATIENTS
      AND METHODS: Thirty-four salivary glands with obstruction were diagnosed as
      having ductal kinks or strictures. Strictures were diagnosed by sialography and
      sialoendoscopy, kinks were diagnosed mainly by sialography, whereas endoscopy was
      used to rule out other pathology and to locate the kink. There were strictures in
      25 salivary glands (14 male and 11 females; aged 25 to 60 years), 14 in the
      parotid and 11 in the submandibular gland, and kinks in 9 salivary glands (5
      males 4 females; aged 40 to 55 years). Seven kinks were found in the
      submandibular gland and 2 in the parotid. Treatment of strictures was performed
      by dilatation procedures with saline under pressure, balloon techniques, and
      forced manipulation. After these procedures, a polyethylene stent was inserted
      for 2 weeks. Kinks were treated by advancement ductoplasty and balloon contouring
      to overcome the acute angle. RESULTS: Twenty of 25 cases of stricture became
      completely asymptomatic in a follow-up of 8 to 36 months after treatment. In 4
      cases, further revisional dilatation was needed, and in 1 case treatment failed
      and the gland had to be removed. All 9 cases of kinks became completely
      asymptomatic in a follow-up of 6 to 24 months after treatment. CONCLUSION:
      Strictures and kinks should be considered when salivary gland obstruction is
      present without sialolithiasis.

PMID- 11326367
TI  - Use of Gore-Tex tubing as a conduit for inferior alveolar and lingual nerve
      repair: experience with 6 cases.
AB  - PURPOSE: This report evaluates treatment outcomes associated with the use of Gore
      Tex (GT; W.L. Gore & Associates, Flagstaff, AZ) vein graft tubing as a conduit
      for repair of inferior alveolar nerve (IAN) and lingual nerve (LN) continuity
      defects. PATIENTS AND METHODS: Six patients (5 female and 1 male) with painful
      dysesthesia secondary to injuries of the IAN (n = 3) or LN (n = 3) underwent
      surgical exploration and resection of pathologic tissue. Reconstruction of the
      resultant continuity defects was performed using 3-mm diameter GT tubing sutured
      to the epineurium of the proximal and distal nerve trunks. Nerve reconstruction
      was performed an average of 20 months after injury (range, 4 to 48 months).
      Patients were tested before and after surgery with the following tests:
      subjective pain level using an analogue scale, sharp stimulus, touch, cold
      sensation, directional sense, and 2-point discrimination. RESULTS: Four patients
      reported no change in subjective pain level, and 2 patients had minimal decrease
      in pain. Two patients reported some sensation to sharp stimulus, and 1 patient
      was hypersensitive. Three patients responded to touch, and 3 had no response.
      Four patients had no response to cold sensation, and 2 had a delayed response.
      Only 1 patient could detect brushstroke direction. Three patients had no response
      to 2-point discrimination, and 3 responded at greater than 20 mm. CONCLUSIONS:
      Use of GT tubing in this group of patients produced poor clinical outcomes and is
      not recommended for nerve reconstruction of IAN and LN continuity defects.

PMID- 11326369
TI  - Accuracy of histologic grading of synovial inflammation in temporomandibular
      joints with internal derangement using Gynther's system.
AB  - PURPOSE: The purpose of this study was to evaluate the accuracy of the system by
      Gynther et al (J Oral Maxillofac Surg 56:1281, 1998) for histologic grading of
      synovial inflammation in the temporomandibular joint (TMJ) in arthroscopically
      obtained synovial biopsy specimens. PATIENT AND METHODS: Thirty-three human TMJ
      synovial biopsy specimens from patients with internal derangement of the TMJ were
      evaluated using the system of Gynther et al. The results were compared
      statistically with the intensity of synovitis seen arthroscopically using
      Spearman ranked correlation coefficient. RESULTS: In 2 of the 3 parameters
      tested, a statistically significant correlation was found between the histologic
      findings by the system of Gynther et al and arthroscopic findings using the scale
      of Murakami et al (J Oral Maxillofac Surg 49:1159, 1991) CONCLUSION: These
      results suggest that histologic grading of synovial inflammation by the system of
      Gynther et al has considerable accuracy. However, more investigations are
      necessary to confirm the results.

PMID- 11326371
TI  - Endoscopic approach to the ramus/condyle unit: Clinical applications.
AB  - PURPOSE: The purpose of this report is to describe use of an endoscopic technique
      for exposure of the mandibular ramus/condyle unit (RCU) to facilitate
      reconstructive jaw procedures. PATIENTS AND METHODS: This is a retrospective
      evaluation of 10 patients with diagnoses of idiopathic condylar resorption (n =
      2), subcondylar fracture (n = 5), mandibular prognathism (n = 1), condylar
      hyperplasia (n = 1), and mandibular asymmetry (n = 1), who underwent endoscopic
      exposure of the RCU. RESULTS: All 10 patients had successful reconstruction of
      the RCU using the endoscopic approach. The procedures performed included the
      following: condylectomy (n = 5 sides), costochondral graft reconstruction (n = 4
      sides), reduction of subcondylar fracture (n = 5 sides), and mandibular ramus
      osteotomy (n = 4 sides). Mean operating time was 84 minutes. No patients had
      marginal mandibular nerve weakness or other complications. CONCLUSION: This case
      series demonstrates the feasibility of endoscopic access to the RCU. The
      procedures can be performed with no increase in operative time and with minimal
      morbidity.

PMID- 11326372
TI  - The effect of precise reattachment of the mentalis muscle on the soft tissue
      response to genioplasty.
AB  - PURPOSE: This study compares vertical and horizontal profile changes of the lower
      lip and chin after genioplasty with or without precise reattachment of the
      mentalis muscle. PATIENTS AND METHODS: Ten patients in whom the mentalis muscle
      was isolated, identified, marked, and precisely reapproximated comprised the
      study group. Eleven patients treated without precise reattachment of the mentalis
      comprised the control group. Preoperative (3 to 6 days before the surgery) and
      postoperative (6 months after surgery) lateral cephalograms were analyzed to
      assess the horizontal and vertical soft tissue changes of the lower lip and chin
      area. RESULTS: All the significant changes in the present study were noted in the
      vertical parameters. In most of the study group, the length of the lower lip was
      either maintained or increased. In the control group, the lower lip length was
      either preserved or decreased. The mean vertical difference between the 2 groups
      was nearly 6 mm. Consequently, the study group displayed the same or less of the
      lower incisors postsurgery compared with the original presurgery exposure in the
      rest position. The opposite was true for the control group, in which the exposure
      of the lower incisor crowns at rest increased. Similar changes were noticed in
      the distance from the vermilion to the reference plane. The vertical position of
      the soft tissue supramentale remained unchanged in the study group, whereas in
      the control group the soft tissue supramentale was located in an inferior
      position (mean = 2.14 mm). The clinical expression of this phenomena is chin
      ptosis. CONCLUSIONS: Precise reattachment of the mentalis muscle during an
      intraoral surgical approach produces a superior result.

PMID- 11326374
TI  - Adjunctive hyperbaric oxygen in irradiated patients requiring dental extractions:
      outcomes and complications.
AB  - PURPOSE: This study assessed complications of hyperbaric oxygen (HBO) therapy,
      potential predictors of poor outcome, and treatment outcomes in irradiated
      patients undergoing dental extractions. PATIENTS AND METHODS: This was a
      prospective, descriptive study of 40 consecutive patients treated with HBO before
      and after dental extractions in an irradiated field. All patients had radiation
      caries; none had osteoradionecrosis (ORN). All were prescribed a protocol of 20
      pre-extraction and 10 postextraction HBO treatments at 2.4 ATA for 90 minutes.
      Potential risk factors for poor healing and risk factors for complications were
      identified. All complications were recorded. Extraction site healing was
      evaluated at the conclusion of HBO therapy, at 1 month, and 1 year later.
      RESULTS: There were no serious complications. There was no correlation between
      preidentified risk factors and poor healing. At 1 year, 98.5% of all extraction
      sites were healed. Patients who did not heal were an average of 8 years since
      radiation, compared with 3.3 years for those who healed (P <.001). CONCLUSION:
      Use of HBO is associated with a very low incidence of ORN at 1-year follow-up.
      However, the time since radiation has a positive correlation with risk for ORN.

PMID- 11326376
TI  - Preoperative determination of the location of parotid gland tumors by analysis of
      the position of the facial nerve.
AB  - PURPOSE: This study examined the usefulness of anatomic lines in predicting the
      intraparotid course of the facial nerve. MATERIALS AND METHODS: To make the
      comparison, 3 lines were drawn on 69 transverse sections of 5 cadaver heads.
      Then, the shortest and the longest distance from the lines to the facial nerve
      were measured. RESULTS: Of the tested lines, the one that connects the most
      dorsal point on the ipsilateral half of a vertebra to the dorsal side of the
      retromandibular vein had the shortest distance to the facial nerve. It also ran
      more parallel to the facial nerve than the other 2 lines. CONCLUSIONS: Because
      the line that connects the most dorsal point on the ipsilateral half of a
      vertebra to the dorsal side of the retromandibular vein best predicts the
      intraparotid course of the facial nerve, it might be useful in assessing whether
      parotid tumors are located in the superficial or deep lobe.

PMID- 11326378
TI  - Histologic study of the bone adjacent to titanium bone screws used for mandibular
      fracture treatment.
AB  - PURPOSE: Titanium miniplates have been widely used in mandibular fracture
      fixation because of their strength and excellent biocompatibility. However, the
      condition of the bone adjacent to titanium bone screws has not been clarified.
      This study histologically examined the bone-screw interface in patients treated
      for mandibular fractures. PATIENTS AND MATERIALS: Specimens were obtained from 14
      patients, and the undecalcified sections were stained by the toluidine blue and
      Levai Laczko methods and examined with light microscopy. The mean ratio of direct
      contact between the bone and the titanium bone screw surface was also analyzed
      using a computer-aided image analyzer. RESULTS: The formation of new bone was
      observed around the titanium bone screws in all cases. In areas of cortical bone,
      partial interposition of soft tissues was rarely observed. However, in areas of
      cancellous bone, partial interposition of soft tissues was seen, and bone
      resorption between the bone and soft tissues was noted. The mean ratio of direct
      contact between all of the adjacent bone and the surface of the titanium bone
      screws was 64.4%. The mean ratio of direct contact between cortical bone and the
      titanium bone screws was 82.4%. Black particles were observed in the bone and
      soft tissues around the titanium bone screws, and multinuclear giant cells
      resembling macrophages were observed near these particles. CONCLUSION: Titanium
      bone screws used for mandibular fracture fixation develop almost complete contact
      with new bone. Some metalosis is present.

PMID- 11326380
TI  - Mandibular distraction force: laboratory data and clinical correlation.
AB  - PURPOSE: In vitro data were collected to measure torque-force values of an
      internal distraction device. The measurements were correlated with in vivo torque
      readings in an attempt to better understand the force required to distract the
      osteogenic bone callus of the human mandible during distraction osteogenesis.
      METHODS AND MATERIALS: Five internal craniofacial distraction devices were
      mounted on an apparatus to test load limits and torque measurements. The
      apparatus aligned the devices so that weight provided a force opposite and
      parallel to the vector of distraction. Weights were added in 5-lb increments, and
      the devices were activated 0.5 mm for each torque reading. Torque readings were
      obtained from a calibrated torque wrench. Measurements were plotted on a graph
      and correlated with clinical torque readings obtained from 8 patients undergoing
      mandibular lengthening. RESULTS: The average torque for distracting the human
      mandible 0.5 mm twice a day was 4.2 +/- 1.6 Newton-centimeters (N-cm). The
      average slope of the in vitro data shows that 4.2 N-cm of torque is equivalent to
      a force of 35.6 N. The average force of device failure was 235.8 N. CONCLUSION:
      Torque-force diagrams offer an effective means for calibrating safety margins and
      load capabilities for internal distraction devices. Quantification of axial
      forces encountered in mandibular lengthening will help contribute to the overall
      understanding and biomechanics of mandibular distraction osteogenesis.

PMID- 11326382
TI  - Clinical controversies in oral and maxillofacial surgery. Part I: A positive view
      of managed health care.

PMID- 11326383
TI  - Clinical controversies in oral and maxillofacial surgery. Part II: A negative
      view of managed health care.

PMID- 11326384
TI  - Development of an oral and maxillofacial surgery outcomes system for anesthesia
      and third molar removal: results of alpha and beta testing.

PMID- 11326385
TI  - Life-threatening cervicofacial infection in a child with hyperimmunoglobulin-E
      syndrome.

PMID- 11326386
TI  - Mandibular resorption due to progressive systemic sclerosis: a case report.

PMID- 11326387
TI  - Leiomyosarcoma of the maxillary sinus with cervical lymph node metastasis.

PMID- 11326388
TI  - Metastatic prostatic carcinoma presenting as cervical lymphadenopathy.

PMID- 11326389
TI  - Osteosarcoma of the mandibular condyle: case report.

PMID- 11326390
TI  - Male breast cancer with maxillofacial metastasis: case report.

PMID- 11326391
TI  - Amelanotic melanoma of the palate: report of case.

PMID- 11326392
TI  - Carcinosarcoma (malignant mixed tumor) of the parotid gland: a case report.

PMID- 11326393
TI  - Human dura mater and Creutzfeldt-Jakob disease.

PMID- 11326395
TI  - Partnering for injury prevention: evaluation of a curriculum-based intervention
      program among elementary school children.
AB  - A randomized pretest and posttest comparative design was used to evaluate the
      outcome of implementing Think First for Kids (TFFK), an injury prevention program
      for children grades 1, 2, and 3, among intervention and controls schools. The
      study showed that children often lack basic knowledge regarding safety and do not
      recognize behaviors considered high risk for injury. By using multivariate
      analysis, the intervention children had a significantly greater increase in
      knowledge about the brain and spinal cord and safe behaviors to prevent traumatic
      injury, and a decrease in self-reported, high-risk behaviors (p < .001) when
      compared with control subjects, adjusting for the covariates gender,
      socioeconomic status, and race/ethnicity. African American and Hispanic children,
      although displaying the lowest test scores at baseline, had the largest absolute
      improvement in posttest scores. The TFKK prevention program addresses the leading
      causes of trauma among children including sports, motor vehicle crashes, falls,
      drowning, and pedestrian injuries.

PMID- 11326396
TI  - Focus groups with African American adolescents: enhancing recruitment and
      retention in intervention studies.
AB  - This study explores African American adolescents' perceptions about recruitment
      and retention strategies for intervention studies. Fifteen African American
      adolescents, ages 13 and 17 years, participated in this focus group study.
      Adolescents attended one of three groups which varied by size, gender, and the
      type of chronic condition: well adolescents (n = 7), adolescents with sickle cell
      disease (n = 5), and adolescents with diabetes (n = 3). Each group of adolescents
      participated in two group sessions. Content analyses of the two major categories
      in the study, recruitment and retention, yielded 10 themes. These themes included
      adolescents' (1) knowledge about their disease; (2) attitudes and expectations of
      self-care classes; (3) expectations about the research interventions; (4)
      instructor characteristics; (5) relationships with the researchers; (6)
      logistical considerations, such as time, location, and setting of interventions;
      (7) involvement and choice during the intervention; (8) relationships with other
      teens; (9) incentives for participation, such as food, fun, and money; and (10)
      the role of health care providers in recruitment and retention for research
      studies.

PMID- 11326397
TI  - Childhood farm injuries in Old-Order Amish families.
AB  - Unintentional injuries are the leading cause of death and disabilities in the
      United States among children, with the incidence even greater among children who
      live on a farm. Information exists about farming accidents on mainstream U.S.
      farms; however, little is known about the Amish farms. The purpose of this study
      was to investigate injuries among Old-Order Amish in Pennsylvania. Teachers in
      Amish schools were surveyed about their experiences with accidents/injuries among
      children on the farm. Seventy percent of the teachers reported a childhood farm
      injury in their family, with the majority attributing this to farm animals.
      Injuries may be preventable if age-appropriate tasks are assigned to children and
      they are properly supervised.

PMID- 11326398
TI  - School-aged homeless sheltered children's stressors and coping behaviors.
AB  - The purpose of this study was to examine the stressors and coping behaviors of
      school-aged homeless children staying in shelters. A secondary analysis of
      interview data from 30 children, between the ages of 8 to 12 years, was used to
      delineate the stressors and coping behaviors. Homeless, family, self, peer,
      school, and violent behavior were the stressor categories derived from content
      analysis. The children expressed more stresses in the homeless, family, and self
      categories than in the other 3 categories. The coping behaviors from the content
      analysis were categorized by using Ryan-Wenger's (1992) coping taxonomy. The
      majority of the children's coping responses were in the social support, cognitive
      avoidance, and behavioral distraction categories. Nurses should assess each
      child's stressors and coping behaviors when providing care to homeless children,
      and assist the child in alleviating some stressors by strengthening one's coping
      behaviors.

PMID- 11326399
TI  - Hospitalized children with chronic illness: parental caregiving needs and valuing
      parental expertise.
AB  - Parents who care for a child with a chronic illness are forced to relinquish much
      of the control of the child's care when the child is hospitalized. By using the
      family systems theory as the underlying framework, the amount of control that
      parents of children with chronic illness wanted over their hospitalized child's
      care, and the degree to which parents felt health care professionals valued their
      expertise, was examined in a national sample of 50 parent caregivers.
      Participation in information sharing and technical care were areas over which
      parents wanted the most control. Nurses and attending physicians were rated
      highest in valuing parental expertise. Content analysis of an open-ended question
      on parental control revealed that parents felt a higher quality care was given at
      home than in the hospital; nurses were too busy or understaffed to provide
      optimal care in the hospital; and the child's control of care and decision making
      should increase as the child grew older.

PMID- 11326400
TI  - Advanced practice in pediatric nursing: blending roles.
AB  - In the past, pediatric advanced practice nurse's roles were the Clinical Nurse
      Specialist (CNS) in the inpatient setting and the Nurse Practitioner (NP) in the
      outpatient setting. With health care system changes, such as the shifting and
      blurring boundaries between inpatient and outpatient care, changes were required
      in the graduate curricula to blend the CNS and NP roles into an advanced practice
      nurse (APN) role. This article describes the model at Rush University, the
      advantages of the CNS/NP blended role, the revised APN curriculum, and examples
      of blended-role APNs in action. The curriculum change to blend the CNS/NP roles
      addresses the need for the blended APN role in changing health care systems.

PMID- 11326402
TI  - Since 1976, the New Jersey Foundation of Dentistry for People With Disabilities
      "Campaign of Concern" has improved the oral health of thousands of
      developmentally-disabled children and adults.

PMID- 11326401
TI  - Qualitative analysis of the care of children in hospital in four countries-Part
      1.
AB  - As part of a large study of the care of children in Australian, British,
      Indonesian, and Thai hospitals, qualitative methods were used to examine
      differences influenced by culture. Two groups were surveyed: parents of
      hospitalized children, and staff caring for them. Vignettes were used to invoke
      discussion, and content analysis was used to examine the data. Subjects were
      interviewed singly, or in focus groups. These interviews were audiotaped and
      transcribed verbatim. The data were explored by using content analysis to extract
      themes of understanding of cultural experiences. This article is the first of a
      two-part series, and includes a review of the literature, description of the
      methods used, and results of the parents' interviews. The staff results and
      discussion will be published in Part 2. Analysis revealed that parents in all
      countries were primarily concerned with treating the child's illness and the
      child's recovery. Parents were concerned with their work (employment), but this
      was a much larger consideration in Indonesia and Thailand, where no social
      security systems exist, than in Australia and Britain. Communication with staff
      was the most commonly mentioned theme for parents, indicating that irrespective
      of the culture in which the care was given, good communication between parents
      and staff was of paramount importance.

PMID- 11326403
TI  - Global antibiotic resistance and its impact on the dental community.

PMID- 11326404
TI  - Oral pathology quiz #30. Case number one. Peripheral ossifying fibroma.

PMID- 11326405
TI  - Oral pathology quiz #30. Case number two. Erythema multiforme.

PMID- 11326406
TI  - Oral pathology quiz #30. Case number three. Adenoid cystic carcinoma.

PMID- 11326407
TI  - Oral pathology quiz #30. Case number four. Odontoma.

PMID- 11326408
TI  - Climax in America. Part V: Dental millennium series.

PMID- 11326409
TI  - Trigeminal nerve injuries.
AB  - Injuries to peripheral branches of the trigeminal nerve are relatively uncommon;
      however, they are fairly debilitating to the patient when they do occur. Treating
      clinicians should evaluate and document baseline neurosensory testing results on
      patients and perform serial examinations approximately every two weeks. If there
      are no changes after one month, consideration should be given for referral to an
      oral and maxillofacial surgeon trained in trigeminal nerve microsurgery. Many
      patients will go on to spontaneous recovery; however, a number will require
      microsurgery. It is prudent for the treating clinician to recognize, document and
      discuss the injury with the patient prior to referring to the oral and
      maxillofacial surgeon trained in microsurgery.

PMID- 11326410
TI  - The Web is key to growth.

PMID- 11326411
TI  - The age of quackery.

PMID- 11326412
TI  - News from Procter and Gamble (P&G) introducing Crest Whitestrips, their new over
      the-counter whitening product.

PMID- 11326413
TI  - Medicare and Medicare supplement: change, change, and more change.

PMID- 11326414
TI  - Water line biofilm dangers--a tempest in a teapot.

PMID- 11326415
TI  - A research model for dental science.

PMID- 11326416
TI  - Personal digital assistants (PDAs). An asset to managing healthcare.

PMID- 11326417
TI  - Orofacial pain emerging as a dental specialty.
AB  - The emerging field of orofacial pain was considered by the American Dental
      Association for full status as a new dental specialty. While the recognition of
      orofacial pain as a specialty was denied, the American Academy of Orofacial Pain
      plans to continue its efforts. Many recent advances in the neuroscience of
      orofacial pain have led to treatments that provide significant relief for
      patients with chronic orofacial pain disorders. However, access to this care has
      been limited, leaving many patients to suffer. Dentists are generally supportive
      of the efforts to develop oral pain treatment into a specialty because the field
      will provide benefits for both dentists and their patients. A recent survey of
      805 individuals who reported having a persistent pain disorder revealed that more
      than four out of 10 people have yet to find adequate relief, saying their pain is
      out of control--despite having the pain for more than five years and switching
      doctors at least once. "This survey suggests that there are millions of people
      living with severe uncontrolled pain," says Russell Portenoy, MD, president of
      the American Pain Society. "This is a great tragedy. Although not everyone can be
      helped, it is likely that most of these patients could benefit if provided with
      state-of-the-art therapies and improved access to pain specialists when needed."
      Development of the field of orofacial pain into a dental specialty has been moved
      primarily by the fact that historically, patients with complex chronic orofacial
      pain disorders have not been treated well by any discipline of healthcare. Recent
      studies of chronic orofacial pain patients have found that these patients have a
      higher number of previous clinicians and have endured many years with pain prior
      to seeing an orofacial pain dentist (see Figure 1). Complex pain patients and the
      clinicians who see them are often confused about who they should consult for
      relief of the pain. Treatment for those patients within the existing structure of
      dental or medical specialties has been inadequate, with millions of patients left
      suffering. Insurers are also confused with regard to reimbursement and may make
      decisions to exclude treatment for orofacial pain disorders under both dental and
      medical policies. However, dentistry has taken a leading role in healthcare to
      address the national problem of developing the field of orofacial pain into a
      dental specialty. A study of dentists and dental specialists has shown that there
      is a recognized need and broad support for developing this field into a
      specialty.

PMID- 11326418
TI  - [Regional meeting of the Japanese Society of Otolaryngology. 2000. Abstracts].

PMID- 11326419
TI  - A transgenic mouse model for investigating the response of the upstream region of
      whey acidic protein (WAP) gene to various steroid hormones.
AB  - The limitations of studies of clarification of response elements of whey acidic
      protein (WAP) gene to hormones using mammary cell lines has been shown. We
      studied the response of the upstream region (2.6 kb) of WAP to various steroid
      hormones using gonadectomized mWAP/hGH transgenic mice. Ovariectomy or castration
      for transgenic mice was performed at 10 days or 30 days post partum. Various
      steroid hormones were administered daily for 10 days to the gonadectomized
      transgenic mice after they reached 2 months of age. Prior to the hormonal
      administration and 24 hr after the final administration, blood was collected and
      the hGH levels in the plasma was measured by RIA. Daily doses of estradiol-17
      beta were significantly more effective at increasing hGH levels in transgenic
      females ovariectomized at 10 days post partum than progesterone of an equal dose.
      A combined dose of progesterone and of estradiol-17 beta significantly amplified
      the increase of hGH levels accompanied by the great development of mammary
      glands, compared to a dose of progesterone alone. Corticosterone induced only a
      slight increase of hGH, while testosterone had no effect. The doses of gonadal
      steroid hormones did not induce an increase in hGH levels and development of
      mammary glands in the castrated transgenic males. The results showed that the
      response of 5' region of WAP requires at least some extended development of the
      mammary gland and that the 2.6 kb upstream region of the exogenous WAP gene
      contained the element responsive to ovarian hormones.

PMID- 11326420
TI  - Postrest contraction in the ventricular papillary muscle of spontaneously
      diabetic WBN/Kob rat.
AB  - In the present study, we investigated the characteristics of the postrest
      contraction (PRC) in chronic diabetic ventricular muscle. We used WBN/Kob rats of
      7-8 weeks as the spontaneously diabetic animal and Wistar rats of 7-8 weeks as
      the control. We found: (1) No significant differences were seen in the amplitude,
      the contracting speed, and the relaxing speed of electrically stimulated twitch
      tension between control and WBN/Kob rats. In addition, the relationship between
      amplitude of twitch tension and stimulus cycle lengths (0.2-5 sec) was very
      similar in both animals. (2) The ratios of the first twitch tension (T1) of PRC
      with various rest intervals (5-600 sec) to the steady-state tension (Tss) were
      significantly smaller in the diabetic rats than in the controls. (3) When the
      preparation was stimulated at shorter cycle lengths, the recovery process of PRC
      was separated into at least two components (fast and slow components). In the
      diabetic rats, the time constant (tau) of both components was significantly
      longer than in controls. (4) After caffeine (10(-3) M) treatment, tau of the fast
      component in the control rats became longer, whereas it remained unchanged in
      diabetic rats. These findings suggest a dysfunction of the intracellular calcium
      handling system in spontaneously diabetic heart that is likely to include
      impaired calcium sequestration and/or extrusion.

PMID- 11326421
TI  - Induction of drug metabolism-related enzymes by methylcholanthrene and
      phenobarbital in transgenic mice carrying human prototype c-Ha-ras gene and their
      wild type littermates.
AB  - Transgenic mice hemizygously carrying human c-Ha-ras proto-oncogene, Tg-rasH2
      show very sensitive and facilitated carcinogenicity to various carcinogens. In
      this study, activities of certain enzymes related to drug metabolism and energy
      metabolism were measured in microsome and cytosol fractions of livers of Tg-rasH2
      mice and their wild type littermates with both sexes treated with 3
      methylcholanthrene (MC) and phenobarbital (PB). Aminopyrine N-demethylase
      activities increased significantly in livers of all mice treated with PB. MC and
      PB treatments induced significant increases in activities of UDP
      glucuronosyltransferase and S-adenosyl homocysteinase compared to those in the
      non-treated groups in microsome fractions from all mice. In cytosol fractions of
      livers of all mice, glutathione S-transferase activity was significantly induced
      in the PB treated groups. There were no significant differences in activities of
      lactate dehydrogenase, glucose 6-phosphate dehydrogenase, pyruvate kinase and
      glucose 6-phosphatase related to energy metabolism in livers and kidneys among
      all mice. Tg-rasH2 mice showed stable activities of enzymes related to drug
      detoxication and energy metabolism similar to those of non-transgenic mice. These
      results suggest that the human c-Ha-ras transgene may not affect drug metabolism
      related enzymes, and the facilitated carcinogenic response in the Tg-rasH2 mouse
      is not due to these enzymatic disorders.

PMID- 11326422
TI  - Establishment of a Tcrb and Trp53 genes deficient mouse strain as an animal model
      for spontaneous colorectal cancer.
AB  - A congenic C57BL/6JJcl-Tcrbtm1MomTrp53tm1 (Tcrb-/-:Trp53-/-) mouse lacking T-cell
      receptor beta chain (TCR beta) and transformation related protein 53 (p53) has
      been established at the N8th generation of backcrossing male Tcrb-/-:Trp53-/-
      mice, which had been obtained by mating a Tcrb-/- mouse with a Trp53-/- mouse,
      with female C57BL/6JJcl mice. In the mice deficient for the both genes,
      occurrence of tumor masses was observed mostly in the cecum with high frequency
      as examined at 3 months of age. The majority of the masses had histologic
      features of hyperplasia or dysplasia while occasional lesions were noted to be
      adenocarcinomas invading the submucosa (invasive adenocarcinoma). As examined at
      4 months of age and thereafter, all mice had 4-5 colorectal tumors per animal,
      the lesions being located mainly in the cecum and, histopathologically, all the
      obvious neoplastic growths in the regions examined were invasive adenocarcinomas.
      The Tcrb and Trp53 genes deficient mouse strain which develops spontaneous
      colorectal carcinoma with fairly high frequency at early age would be useful as
      an animal model for colorectal cancer.

PMID- 11326423
TI  - Effect of M2 and M3 muscarinic receptors on airway responsiveness to carbachol in
      bronchial-hypersensitive (BHS) and bronchial-hyposensitive (BHR) guinea pigs.
AB  - The expression balance of M2 and M3 muscarinic receptor subtypes on the
      pathogenesis of airway hyperresponsiveness was investigated by using two
      congenitally related strains of guinea pigs, bronchial-hypersensitive (BHS) and
      bronchial-hyposensitive (BHR). CCh-induced airway responses in vivo and in vitro
      were investigated by comparing the effects of muscarinic receptor subtype
      antagonists, and the relative amounts of M2 and M3 muscarinic receptor mRNA in
      tracheal smooth muscle and lung tissue were investigated. After treatment with
      muscarinic receptor subtype antagonists, the ventilatory mechanics (VT, Raw, and
      Cdyn) of response to CCh aerosol inhalation were measured by the
      bodyplethysmograph method. The effects of these antagonists on CCh-induced
      tracheal smooth muscle contraction were also investigated. The effects of M2
      muscarinic receptor blockade were less but the effects of M3 muscarinic receptors
      blockade on the airway contractile responses were greater in BHS than in BHR. In
      M3 muscarinic receptor blockades, CCh-induced tracheal contractions in BHS were
      significantly greater than those in BHR. In tracheal smooth muscle from BHS, the
      relative amount of M2 muscarinic receptors mRNA was less but that of M3
      muscarinic receptor mRNA was more than those in BHR. These results suggest that
      the high ACh level as a consequence of dysfunction of M2 muscarinic autoreceptors
      and the excessive effect of M3 muscarinic receptors on the airway smooth muscle
      may play an important role in the pathogenesis of airway hyperresponsiveness.

PMID- 11326424
TI  - Sex and strain differences in the brush border and PAS-positive granules and
      giant bodies of the mouse renal S3 segment cells.
AB  - We recently demonstrated sexual dimorphism in the S3 segment of the ICR mouse
      kidney, as differences in periodic acid Schiff (PAS) staining on the brush border
      and the number and size of PAS-positive granules. However, whether these sex
      dependent features in the S3 segment of the mouse kidney occur only in the ICR
      strain or are a general feature also observed in other strains is unclear. In the
      present study, we examined the renal S3 segment of the ICR, BALB/c, C57BL/6,
      C3H/He and DBA/2 mice strains, which are commonly used in laboratory experiments.
      PAS staining of the brush border in females of all strains was more intense than
      that of males, and PAS-positive granules were detected in all females. In male
      groups, PAS-positive granules were detected in the DBA/2 strain only, but their
      number was very few. In addition, PAS-positive giant bodies, larger than the
      nuclear size, were detected in females except those of the C57BL/6 strain.
      Histometrical investigation demonstrated apparent strain differences in a number
      of PAS-positive granules and PAS-positive giant bodies. The ultrastructural and
      cytochemical investigations suggest that the PAS-positive granules and PAS
      positive giant bodies were multilamellar lysosomes. We propose that the present
      findings are significant for comparative morphology in laboratory animal science.

PMID- 11326425
TI  - Lack of B cell leakiness in BALB/cA-nu, scid double mutant mice.
AB  - BALB/cA mice homozygous for both nu and scid mutations (BALB/cA-nu/nu, scid/scid)
      were developed by mating between BALB/cA-scid and BALB/cA-nu. These mice have
      greater longevity than C.B-17-scid because no thymic lymphoma occurs in them
      unlike in the latter. C.B-17-scid is known to show the leaky phenomenon in which
      a few clones of functional T and B cells develop in aged C.B-17-scid.
      Unexpectedly, the leaky B cells and T cells were absent or suppressed in BALB/cA
      nu, scid mice when cytokine expressions were determined by RT-PCR, lymphocyte
      phenotypes by flow cytometry and serum immunoglobulin levels by ELISA. These
      results indicate that B cell leakiness may be induced by leaked T cells. BALB/cA
      nu, scid mice may be useful as a recipient in allo- and xeno-transplantation
      experiments because of the absence of both thymic lymphomas and leakiness, in
      addition to lack of hair.

PMID- 11326426
TI  - A histological study on the coronary artery of the indigenous black Bengal goat
      in Bangladesh.
AB  - The coronary artery of the black Bengal goat was studied by light microscopy. The
      wall of the coronary artery consisted of the tunica intima, tunica media and
      tunica externa. The tunica intima consisted of a single layer of flattened
      endothelium. The tunica media was well-developed and composed of mainly of smooth
      muscle cells together with some fine elastic fibers. The tunica externa consisted
      of predominant collagen fibers, and some elastic fibers and smooth muscle cells.
      Elastic fibers in the tunica externa formed a circular arrangement around the
      tunica media. Sex differences were not observed. The media with well-developed
      smooth muscle cells may be responsible for changes in functional physiological
      conditions of the heart.

PMID- 11326427
TI  - Senile plaques in an aged western lowland gorilla.
AB  - Senile plaques (SPs) were found in the cerebral cortex of a 44-year-old Western
      lowland gorilla (Gorilla gorilla gorilla). All the SPs were obtained as dense
      assemblies consisting of fibrous materials by silver impregnation, but were not
      detected by Congo red. More SPs were detected by immunostaining for amyloid beta
      protein (A beta) and a half of A beta-positive-SPs were also immunoreactive for
      apolipoprotein E. Moreover, all SPs were immunoreactive for A beta 42 and A beta
      43, but not for A beta 40. SPs also did not contain A beta precursor protein
      positive structures. These findings suggested that SPs in this case were diffuse
      plaques. To our knowledge, this is the first report of SPs in the gorilla.

PMID- 11326428
TI  - Cryopreservation and transport of mouse spermatozoa at -79 degrees C.
AB  - In the present study, 2 experiments were carried out. In experiment 1, mouse
      spermatozoa were frozen and stored in an ultra-low temperature freezer maintained
      at -79 degrees C, from 1 week to 8 months. In vitro fertilization rates of the
      frozen-thawed sperm after 1 week and 4 months of storage were high at 71 and 71%,
      respectively. These values did not differ significantly from the value (73%) of
      the control stored at -196 degrees C. In contrast, the 8-month storage rate was
      significantly lower at 51%. In experiment 2, frozen spermatozoa were transported
      in a Styrofoam box packed in dry ice from Hokkaido to Tokyo. In vitro
      fertilization rate of frozen-thawed sperm after transport at -79 degrees C was
      high at 88%, which was not significantly different from that (84%) of the
      transported control at -190 degrees C. After transferring two-cell embryos
      derived from frozen spermatozoa to recipients, 37-62% of the embryos developed
      into offspring in both experiments. These results indicate that mouse spermatozoa
      can survive cryopreservation in an ultra-low temperature freezer (-79 degrees C)
      for up to 4 months and transport at -79 degrees C.

PMID- 11326429
TI  - Effects of age and weaning on the immature rat uterotrophic assay using
      ethynylestradiol.
AB  - The purpose of this study was to evaluate the most appropriate rat age for the
      start of administration, and the effect of weaning, in the immature rat
      uterotrophic assay using ethynylestradiol (EE). Animals weaned on postnatal day
      (PND) 20 were administered subcutaneously EE at doses of 0.06-6 micrograms/kg/day
      for 3 days beginning on PND 21, 23 or 25. EE at the same doses was also
      administered to rats weaned on PND 17 or 20 from PND 21 for 3 days. Although
      uterine weight was significantly increased in the rats given 0.6-6 micrograms/kg
      EE in both of the studies, the percentage increase relative to the control in
      each group given EE from PND 21 and weaned on PND 20 was higher than in those
      groups given EE from PND 23 or 25, and the group weaned on PND 17.

PMID- 11326431
TI  - Effect of acetylcholinesterase activity on pathogenesis of airway
      hyperresponsiveness in guinea pigs.
AB  - To clarify the effect of acetylcholinesterase (AChE) on the pathogenesis of
      airway hyperresponsiveness, AChE activities in tracheal smooth muscle and lung
      tissue from congenitally bronchial-hypersensitive (BHS) and bronchial
      hyposensitive (BHR) guinea pigs were compared. For this purpose, AChE activities
      were determined by measuring the rate of absorbance of tissue homogenate.
      Relative amounts of AChE mRNA were also evaluated by the RT-PCR method. In both
      tracheal smooth muscle and lung tissue from BHS, the AChE activity and the
      relative amount of AChE mRNA were less than those in BHR. These results suggest
      that the reduced AChE activity is at least a candidate for inducing airway
      hyperresponsiveness.

PMID- 11326430
TI  - Possible role of peripheral CD14low monocytes in the development of collagen
      induced arthritis in cynomolgus monkeys (Macaca fascicularis).
AB  - The changes in levels of peripheral major lymphocyte subsets were monitored with
      10 adult cynomolgus monkeys (5 females and 5 males) during the 9 weeks after
      immunization with chick type-II collagen in Freund's complete adjuvant. Three
      females and 3 males developed overt arthritis determined by swelling of small
      joints and increase of plasma alkaline phosphatase as well as C-reactive protein.
      An increase of CD16+ NK cells was observed in four non-arthritis-developed
      monkeys (two females and two males). There was no significant difference in the
      fluctuation pattern of CD4+ T cell, CD8+ T cell and CD20+ B cell levels between
      arthritis-developed monkeys and non-developed ones. In addition, the percentages
      of CD45RA+ CD4+ T cells to total CD4+ T cells, CD28- CD8+ T cells to total CD8+ T
      cells, and IgD- B cells to total B cells did not significantly differ between
      them. On the other hand, a significant increase was demonstrated in CD14-positive
      cells at 3 weeks after immunization in only arthritis-developed monkeys
      regardless of sex. The expression of CD14 antigen on the surface of increased
      cells was low in comparison with those appearing in blood obtained before
      immunization. In addition, increased CD14low cells showed no response to LPS
      stimulation. However, there was no significant difference in antibody titer to
      both chick type-II and monkey type-II collagen between arthritis-developed
      monkeys and non-developed ones. These results suggest that an increase in number
      of CD14low monocytes with immature function might be a part of the autoimmune
      response, and that the appearance of these cells is of pathogenic importance in
      the arthritic process in cynomolgus monkeys regardless of the production of
      autoantibody.

PMID- 11326433
TI  - 47th annual meeting of the Japanese Association for Laboratory Animal Science.
      Tokushima, Japan. May 21-23, 2000. Abstracts.

PMID- 11326432
TI  - The eye lens aplasia (elap) maps to mouse chromosome 2.

PMID- 11326434
TI  - [76th annual meeting of the Japanese Society for Tuberculosis. Okinawa, Japan.
      April 19-21, 2001. Abstracts].

PMID- 11326435
TI  - [From borderline psychoses to personality disorders].

PMID- 11326436
TI  - [Modification and treatment of anti-social personality disorders].

PMID- 11326437
TI  - [Start of personality disorders and its tendency during the developmental stage
      of childhood and adolescence].

PMID- 11326438
TI  - [Position of personality disorders in psychodynamic psychiatry--with special
      reference to its relationship with the concept of borderline psychoses].

PMID- 11326439
TI  - [National Health Insurance coverage for nursing care and the role of psychiatric
      medicine].

PMID- 11326440
TI  - [Japanese Society of Sleep Research--toward the development of science of sleep
      and the establishment of sleep-related medical discipline].

PMID- 11326441
TI  - [A case of 'hallucination of soliloquy' with hypothyroidism induced Hashimoto
      disease. Meaning of psychopathological research about symptomatic psychosis].
AB  - We describe the first reported case of symptomatic psychosis with the
      'hallucination of soliloquy.' A 48[correction of 40]-year-old woman with
      Hashimoto disease exhibited of compulsive checking, mysophobia, and excessive
      hand washing. When these obsessive-compulsive symptoms diminished, she began to
      suffer from the 'hallucination of soliloquy', the automatic flow of meaningless
      words inside her mind. As the 'soliloquy' increased, her mood became unstable and
      she attempted suicide by analgesic ingestion. After this, she was admitted to the
      psychiatric ward of a general hospital. The administration of clomipramine (150
      mg daily) decreased the 'soliloquy' symptoms, but they did not resolve. When
      hypothyroidism became available, thyroid hormone treatment (levothyroxine at 50
      mg daily) was started. Four weeks later, her 'soliloquy' symptoms had almost
      resolved and after three months in a stable state, thyroid hormone treatment was
      stopped and her 'soliloquy' symptoms soon reappeared. After thyroid hormone
      treatment was resumed, her 'soliloquy' symptoms disappeared immediately. Typical
      auditory hallucinations and delusions of reference were not observed throughout
      the clinical course. We speculate that the symptoms were symptomatic psychosis
      induced by hypothyroidism secondary to Hashimoto disease, because the changes of
      her hallucinations were related to free T3 values and the symptoms disappeared
      soon after starting thyroid hormone treatment. The main features of this case
      were 'soliloquy' alternating with obsessive-compulsive symptoms, but her
      'soliloquy' symptoms were thought to be autochthonous ideas rather than obsessive
      thoughts. Furthermore, the symptoms in this case were different from
      schizophrenia, since there was no disturbance of communication, and she had the
      sensation of both speaking and hearing her own voice. The psychopathology of this
      'hallucination of soliloquy' may be related to the theory of 'vocalization of
      background thinking' (N. Nakayasu). Detailed observation of patients with
      symptomatic psychosis and a psychopathological description of their symptoms may
      help to contribute to the etiologic elucidation and treatment of psychosis.

PMID- 11326442
TI  - Provision of extractions by main diagnoses.
AB  - AIMS/OBJECTIVES: The aim of this study was to investigate the association of
      extractions by the diagnoses of caries, pulpal/periapical infection and
      periodontal disease, controlling for visit type, insurance and age. DESIGN: Cross
      sectional analysis of the 1993-94 wave of a longitudinal study. SETTING: Private
      general dental practice. PARTICIPANTS: A random sample of Australian registered
      dentists, (response rate = 74%). METHODS: Practitioners completed service logs
      over one to two typical clinical days. MAIN OUTCOME MEASURE: Percentage of
      patients receiving extractions. RESULTS: Overall, 7.05% of patients received
      extractions, with the highest percentages occurring for persons with caries
      (7.90%), periodontal disease (17.45%) and pulpal/periapical infection (17.54%).
      Odds of extraction were higher at emergency visits for insured and uninsured
      patients compared to non-emergency visits by insured patients, while odds of
      extraction (Logistic regression: OR = Odds ratio; 95% CI) were higher for 18-44
      year-olds with caries (OR = 1.44; 1.09-1.89), for 18-44 (OR = 1.84; 1.34-2.54)
      and 45+ year-olds (OR = 1.83; 1.27-2.63) with pulpal/periapical infection, and
      for 45+ year-olds (OR = 6.82; 4.68-9.95) with periodontal disease. CONCLUSIONS:
      There were different age-specific causes of extraction, controlling for visit
      type and insurance. Effect sizes were highest for pulpal/periapical infection and
      periodontal disease, but caries remained a major cause of tooth loss due to the
      higher prevalence of this condition.

PMID- 11326443
TI  - Occupational hygiene practices of dentists in southern Thailand.
AB  - OBJECTIVES: The aims of this study were to investigate the prevalence and nature
      of infection control, radiation control and handling of mercury, reported by
      dentists in southern Thailand. METHOD: A cross-sectional study with self-report
      questionnaire to all 220 dentists working in 14 provinces in southern Thailand in
      1997. RESULTS: 178 dentists (80.9%) aged 22-54 years responded. All reported
      wearing personal protective measures, at least sometimes and using high level
      disinfection (formerly sterilisation) procedures for handpieces. Most (93.8%)
      reported changing sterilised handpieces for each patient. The most commonly
      reported method of high level disinfection was alcohol (37.1%). Just over two
      thirds (68.0%) reported having HBV vaccination. Most (94.3%) reportedly took
      precautions when radiographs were taken and (89.9%) reported protecting their
      eyes with a UV/blue light shield or filter while using these units. About half of
      dentists (51.7%) reported storing excess amalgam under water compared with 20.1%
      that they stored it in a closed box. 77.7% reported using sealed mercury amalgam
      capsule systems, at least sometimes. Nearly half (47.1%) reported disposing of
      used capsules in the bin. CONCLUSIONS: The present study has indicated that
      occupational hygiene practices of dentists in southern Thailand are generally
      consistent with published guidelines for infection control and also with other
      populations of dentists studied in the areas of infection control and radiation
      protection. Further continuing education and investigation of appropriate
      interventions to promote good occupational hygiene standards may also be needed.

PMID- 11326444
TI  - Cross-infection control in dental practice in the Republic of Ireland.
AB  - OBJECTIVE: The purpose of this study was to examine the infection control
      procedures used in general dental practices in the Republic of Ireland. DESIGN:
      Postal survey. SETTING: The Republic of Ireland. PARTICIPANTS: 250 general dental
      practices. METHODS: Postal questionnaire. MAIN OUTCOME MEASURES: Use of infection
      control procedures; gloves, masks, sterilisation of instruments, staff training.
      RESULTS: A 74% response rate (n = 177), with 162 wearing gloves for all patients,
      97% of whom used latex gloves. Routine glove use by 69% of dental nurses.
      Approximately one third of respondents complained of hand skin irritation
      attributed to the wearing of latex gloves. Routine mask wearing during treatment
      was reported by 68% of respondents. The method of choice for sterilising
      instruments was the steam autoclave for 97%. Time spent on surgery cleaning
      between patients was less than one minute in 12 per cent of practices.
      CONCLUSIONS: Cross-infection control procedures practiced by a high proportion of
      the respondents to the survey conform to guidelines suggested by various
      authorities. Further education may be appropriate in a number of areas such as
      mask wearing and the need to change gloves between patients.

PMID- 11326445
TI  - Dental health and treatment needs among a sample of Bangladeshi medical users
      aged 40 years and over living in Tower Hamlets, UK.
AB  - AIM: To assess the dental health status and treatment needs of Bangladeshi
      medical care users aged 40 years and over and to explore the relationship of oral
      disease status, tobacco usage and paan (betel quid) chewing. DESIGN: Multi-centre
      cross-sectional study. SETTING: General medical practitioners' waiting areas in
      Tower Hamlets, UK. SUBJECTS: 185 Bangladeshi adults aged 40 years and over.
      INTERVENTION: A clinical examination and an interview schedule. MEASURES: Dental
      status, periodontal status, dental plaque, calculus and denture status. Tobacco
      smoking and paan chewing behaviour. RESULTS: The response rate was 74%. 85% of
      participants were dentate with an average number of 24 (SD +/- 5.4) standing
      teeth. The mean DMFT score was 5.38, with missing teeth (3.81) being the major
      component. The decayed component was 0.43 and the filled was 1.14. 46% of
      participants were assessed as being free from gingivitis. Significant
      relationships between chewing paan and aspects of dental and periodontal status
      were found. Impacts of oral health were reported by 45% of the respondents. The
      normative need for dental treatment was 96% with a perceived need of 48%.
      CONCLUSION: There was considerable normative dental need. Whilst caries
      experience was low, there were high levels of periodontal treatment needs. Paan
      chewing was related to aspects of dental and periodontal status.

PMID- 11326446
TI  - Prevalence of oral lesions among a sample of Bangladeshi medical users aged 40
      years and over living in Tower Hamlets, UK.
AB  - AIM: To collect data on the prevalence of oral mucosal lesions among Bangladeshi
      medical care users aged 40 years and over and to explore the relationship of oral
      disease status and tobacco smoking and paan (betel quid) chewing. DESIGN: Multi
      centre cross-sectional study. SETTING: General medical practitioners' waiting
      areas in Tower Hamlets, UK. SUBJECTS: 185 Bangladeshi adults aged 40 years old
      and over. METHOD: An oral mucosal examination, based on WHO criteria and an
      interview. Information on tobacco smoking and paan chewing behaviour was
      collected during the interview. RESULTS: Out of 185 adults there was a response
      rate of 74%. Oral mucosal lesions were observed in 40% of participants. The most
      common lesion was found to be leukoplakia with a prevalence of 25%. Significant
      relationships were found between smoking and the presence of oral pathology and
      between paan chewing with tobacco and the presence of leukoplakia. CONCLUSION: In
      this study of older Bangladeshi medical care users there was a high prevalence of
      oral mucosal lesions. Sensitively tailored health promotion interventions, which
      aim to reduce tobacco use, should be developed for this population.

PMID- 11326447
TI  - Caries risk in patients with thalassaemia major.
AB  - AIM: The aim of this study was to assess the prevalence and distribution of
      dental caries in subjects with thalassaemia major. DESIGN: Clinical examination
      for dental caries, diagnosed according to the WHO criteria. PARTICIPANTS: A total
      of 54 thalassaemic patients, 23 aged 6-9 (14 males and 9 females) and 31 aged 12
      18 (17 males and 14 females) were examined. OUTCOME MEASURES: dmft, DMFT and
      plaque scores. RESULTS: The mean dmft was 6.92 for 6-7 year olds and 4.72 for 8-9
      year olds. The DMFT values were 6.57 and 5.95 for ages 12-14 and 15-18,
      respectively. There was no statistically significant difference in caries
      prevalence (dmft/DMFT) between gender or between primary and permanent teeth.
      Only 17.4 per cent of the children aged 6-9 and 21.4 per cent of 12-18 years olds
      were caries free. The prevalence of dental caries in the thalassaemia patients
      was considerably higher (22.7 per cent) than that reported in a normal Jordanian
      sample (DMFT 6.26 vs 4.84). Very few fillings (1.4 per cent of the examined
      teeth) were observed, indicating a negligible rate of conservative treatment.
      More than half (61.1 per cent) of the patients had poor oral hygiene (plaque
      score > or = 2.0). CONCLUSIONS: The need for effective preventive measures,
      education and dental treatment need to be stressed for this caries risk group.

PMID- 11326448
TI  - Bacterial aerosols in the dental clinic: a review.
AB  - A number of sources of bacterial aerosols exist within and outside the dental
      clinic. The concentration of bacterial aerosols and splatters appears to be
      highest during dental procedures, especially those generated by some procedures
      such as ultrasonic scaling, or using a high speed drill. Several infectious
      diseases could be transmitted to staff and patients by airborne bacterial and
      other contaminants in the dental clinic. Air-conditioning and ventilation systems
      should be regularly maintained to reduce environmental contaminants and to
      prevent recirculation of bacterial aerosols. Pre-procedural rinsing by patients
      with mouthwashes as well as vacuum and electrostatic extraction of aerosols
      during dental procedures could also be employed. Dental staff should also
      consider appropriate immunizations and continue to use personal protective
      measures, which reduce contact with bacterial aerosols and splatters in the
      dental clinic.

PMID- 11326449
TI  - The possibility of previous epidemiological data to serve as baseline for future
      national oral health surveys--a study in Vietnam.
AB  - AIM: The purpose of this paper is to review the most recent epidemiological data
      (1985-2000) on dental caries and periodontal diseases in Vietnam in an attempt to
      obtain a 'baseline' for future national oral health surveys. METHODS: Studies on
      periodontal diseases and caries were included when CPITN and WHO caries criteria
      had been applied and when the sample size was at least n = 200 for each age
      group. RESULTS: Almost all subjects had calculus. The median number of sextants
      with calculus in the 15-19-year- and in the 35-44-year-olds was 4.2 and 5.0,
      respectively. Only 2-7% of the 35-44-year-olds had one or more deep periodontal
      pockets. The estimated DMFT of the 12-, 15- and 35-44-year-olds was 1.8, 2.0 and
      5.4, respectively, in the years around 1990. CONCLUSION: This review shows that
      (often neglected) epidemiological studies from the past on caries and periodontal
      diseases can contain comprehensive data sets that provide an estimate of the past
      oral health status which may serve as a baseline for future national surveys.

PMID- 11326450
TI  - The ethnicity of dental practitioners in the United Kingdom.
AB  - OBJECTIVE: To describe the proportion of dental practitioners, currently
      practising in the UK, who are from different ethnic groups. METHOD: Analysis of
      data from the British Dental Association Omnibus Survey 2000. The sample
      comprised 970 qualified dentists in all fields of practice. FINDINGS: Dental
      practitioners from minority ethnic groups constitute approximately 14% of the
      population of dentists. There has been an increase in the proportion of dentists
      from minority ethnic groups amongst cohorts of dentists qualifying since 1987.
      There is some evidence that dentists from minority ethnic groups are more likely
      to treat patients under NHS payment. CONCLUSIONS: The profession of dentistry in
      the United Kingdom appears to have little problem attracting members of some
      minority ethnic groups in particular those of Indian, Pakistani and Bangladeshi
      origin. Individuals of Black Caribbean and Black African origin are under
      represented.

PMID- 11326451
TI  - Informed consent in dental practice: experiences of Dutch patients.
AB  - AIM: To assess experiences of the Dutch population concerning the implementation
      of some of their rights by dentists. METHOD: A postal questionnaire.
      PARTICIPANTS: All 1,616 participants of the 'Consumer Panel Health Care' in the
      Netherlands. RESULTS: 78.8% of the subjects responded. Patients were satisfied
      with the general information they received from their dentist. Their experiences
      of receiving information about specific legislation-related issues, however, were
      less positive. A considerable percentage of patients indicate that their dentist
      did not always inform them about risks or alternative treatment options.
      CONCLUSION: The autonomy of patients, which is the key principle underlying the
      1995 Medical Treatment Contract Act, can seriously be undermined without making
      available this kind of information.

PMID- 11326452
TI  - A review of the oral health status in Syria.
AB  - AIM: To estimate the prevalence and severity of dental caries and periodontal
      diseases in Syria and to determine possible secular changes in the last two
      decades. METHODS: Epidemiological studies performed between 1980-1999, using the
      WHO criteria for dental caries and the CPITN criteria for periodontal diseases in
      Syria were retrieved and reviewed. RESULTS: The caries experience of 5-year-old
      children was high (dmft of 4.7-5.2). The estimated DMFT score of 12-year-old
      Syrian children was 1.9-2.3. A secular change of the caries experience in the
      last two decades was not apparent. The amount of untreated caries lesions was
      high and had not changed substantially in the last two decades. The D component
      comprised 72-90% of the DMFT of 12-15-year-old children and 26-30% of the DMFT of
      35-44-year-old Syrians. The majority of 15-24-year-olds, and more than 80% of the
      35-44-year-olds had calculus. Despite the widespread and chronic existence of
      calculus, only 3-11% of the 35-44-year-old persons had one or more deep
      periodontal pockets. CONCLUSION: The caries experience in Syria is moderately low
      and does not seem to have changed in the last two decades. The increased output
      of graduate dentists in the last decade has not changed the large amount of
      untreated caries lesions. In Syria, where the prevalence of unmet (caries)
      treatment needs is high, regular removal of calculus (scaling) for the sake of
      preventing periodontal pockets should not have a high priority in the oral health
      services.

PMID- 11326453
TI  - Researching domestic violence against women: methodological and ethical
      considerations.
AB  - The results of three population-based studies on violence against women in
      Nicaragua are compared in this article. Two of the studies were regional in scope
      (Leon and Managua) and focused specifically on women's experiences of violence,
      whereas the third study was a Demographic and Health Survey (DHS) conducted with
      a nationally representative sample of women. The lifetime prevalence estimates
      for women's undergoing physical violence from a partner were significantly higher
      in the Leon study (52 percent) and Managua study (69 percent), compared with that
      given in the DHS (28 percent). Possible explanations for the differences are
      examined through pooled multivariate logistic regression analysis, as well as
      analysis of six focus-group discussions carried out with field-workers and staff
      from the three studies. The most important differences that were found concerned
      ethical and safety procedures and the interview setting. The results indicate
      that prevalence estimates for violence are highly sensitive to methodological
      factors, and that underreporting is a significant threat to validity.

PMID- 11326454
TI  - Childbearing in five Arab countries.
AB  - The life-table technique is used in this study to describe childbearing patterns
      in five Arab countries (Algeria, Egypt, Morocco, Sudan, and Yemen). Two summary
      measures are estimated: the cumulative proportion of women of a given parity
      having a subsequent birth within 60 months of the previous birth (quintum), and
      the median length of the interval between successive births. The analysis
      indicates that in Yemen (where the total fertility rate exceeds seven children
      per woman of reproductive age), women begin childbearing at a relatively early
      age and a large proportion of ever-married women reach high parity at a
      relatively fast pace. Morocco and Egypt (with TFRs of 3.3 and 3.8 children per
      woman, respectively) are characterized by delay in the onset of childbearing, a
      slow pace of childbearing, and a smaller proportion of ever-married women
      reaching high parity. In Algeria and Sudan (with TFRs of 4.4 and 4.6 children),
      delay in the onset of childbearing plays a larger role in fertility reduction
      than do the tempo or the quantum of childbearing.

PMID- 11326455
TI  - Is fertility declining in Benin?
AB  - This study analyzes reproductive changes in Benin, a West African country with
      high fertility and low prevalence of use of modern contraceptive methods, using a
      combination of quantitative and qualitative approaches. Findings indicate that an
      irreversible fertility transition has started as the result of an emerging
      pattern of birth limitation and continued desire for the traditional long birth
      intervals. The data suggest that changes in childhood mortality in combination
      with an increase in women's education, although modest, have created a demand for
      fertility control among women; that induced abortion may be one of the means
      through which such demand is being met, particularly in urban areas; and that the
      economic crisis of the 1980s was the main catalyst that precipitated the onset of
      transition. Changes in reproductive preferences and practice suggest a diffusion
      process, from urban and more educated women to rural and less-educated ones.

PMID- 11326456
TI  - The role of changes in contraceptive use in the decline of induced abortion in
      Turkey.
AB  - The induced abortion rate in Turkey declined from a peak of 4.5 abortions per 100
      women in 1988 to 2.4 in 1998. This study examines the extent to which the decline
      in abortion in Turkey can be attributed to increased use of modern
      contraceptives. Trends in induced abortion rates and in contraceptive use are
      examined among Turkish women together with fertility preferences, changes in the
      contraceptive behavior associated with abortion, and changes in the propensity to
      abort unwanted pregnancies. The analysis includes a number of simulations that
      examine what abortion levels might be in different contraceptive-use scenarios.
      Results indicate that the decline in abortion is due to a decrease in the number
      of abortions associated with traditional method failure. This decrease is related
      to three factors: a shift from traditional method use to modern method use, a
      decline in the traditional method failure rate, and a decline in the proportion
      of pregnancies resulting from traditional method failures that are aborted.

PMID- 11326457
TI  - Correlates of sexual activity and condom use among secondary-school students in
      urban Peru.
AB  - Recent data indicate that adolescent fertility rates in Peru remain high and that
      Peruvian adolescents and young adults account for a disproportionate share of new
      HIV infections. The present study was undertaken to identify key risk and
      protective factors for early sexual activity and unprotected sex among secondary
      school students in nine large cities in Peru. Survey data from 6,962 students
      aged 13-18 are consistent with existing research in indicating that behaviors of
      Peruvian youth are influenced in important ways by many factors. In the present
      study, these included region of residence, family economic position, family
      structure, working for pay, peer behaviors, and self-esteem. Knowledge of
      pregnancy and of the risks of acquiring sexually transmitted diseases and of the
      means of avoiding both did not, however, differentiate risk-takers from non-risk
      takers. The study findings suggest a need for adolescent health programs to
      broaden their focus beyond the immediate proximate determinants of behavior, such
      as sexual and reproductive health knowledge and access to contraceptives, and
      also to target some of the key contextual factors influencing adolescent
      behavior.

PMID- 11326458
TI  - Sterilization and financial penalties imposed on registered peasant couples,
      Hebei Province, China.
AB  - Using fertility survey data from the 1980s for registered Han peasant couples in
      Hebei Province, this study examines whether China's family planning policy
      reflects couples' voluntary compliance with policy regulations, their coercion by
      means of government sanctions, or a combination of both. Three family planning
      regulations are considered: birth-quota status, contraceptive use, and length of
      prior birth interval. The results of the study provide support for both
      compliance and sanction perspectives and suggest that by the late 1980s, the
      state was less willing than it had been previously to negotiate with couples who
      had had three children. Evidence is found of cooperation between couples and the
      state to ensure that each family had at least one son.

PMID- 11326459
TI  - Ghana 1998: results from the Demographic and Health Survey.

PMID- 11326460
TI  - Togo 1998: results from the Demographic and Health Survey.

PMID- 11326461
TI  - The newest addition to the endangered species list: pediatric nurses.

PMID- 11326462
TI  - Children in foster care: a nursing perspective on research, policy, and child
      health issues.
AB  - ISSUES AND PURPOSE: To examine the roles of public policy and poverty on the
      rising number of children in family foster care, and to examine the impact of
      different types of family foster care on children's well-being. CONCLUSIONS:
      Recent changes in welfare legislation increase the likelihood of family poverty,
      with a subsequent increase in the number of children in out-of-home care. Greater
      emphasis needs to be placed on preventing entry into out-of-home care, improving
      the quality of foster care, and giving children a voice in care decisions.
      PRACTICE IMPLICATIONS: Nurses have important roles to play in the prevention of
      family dissolution, the design of healthcare delivery systems for children in
      foster care, in evaluating and educating all types of foster families, and as
      advocates in legal and legislative proceedings.

PMID- 11326463
TI  - Experiences of students in pediatric nursing clinical courses.
AB  - ISSUES AND PURPOSE: Learning may be inhibited if students experience undue stress
      in the clinical setting. This study described the stresses, challenges, and
      emotions experienced by pediatric nursing students. DESIGN AND METHODS: Students
      (n = 75) completed a modified Pagana Clinical Stress Questionnaire at the end of
      their pediatric nursing clinical course. The comparison group of students (n =
      383) was enrolled in nonpediatric clinical courses in the same nursing programs.
      RESULTS: The most stressful aspect of clinical practice was giving medications to
      children. High stress scores were related to more fear and disappointment in
      clinical practice. Students who experienced high stress were less stimulated by
      their clinical activities and developed less confidence in practice. PRACTICE
      IMPLICATIONS: Knowledge of students' perceptions of clinical stress can help
      educators and clinicians promote a positive and rewarding clinical atmosphere.

PMID- 11326464
TI  - Effectiveness of a parent education intervention for at-risk families.
AB  - ISSUES AND PURPOSE: Although many parenting programs exist to prevent child
      maltreatment, few are supported by research evidence. This study explored whether
      parents who completed the Bavolek Nurturing Program improved their parenting
      attitudes. DESIGN AND METHODS: Secondary analysis of data from a larger study
      involved a convenience sample of 154 families from 15 county child maltreatment
      prevention councils. RESULTS: On the pretest, parents demonstrated scores
      associated with maladaptive parenting practices. Posttest scores were consistent
      with nurturing parenting attitudes. PRACTICE IMPLICATIONS: Effective and readily
      accessible parent education programs are highly indicated for prevention of child
      maltreatment. It is important for nurses to have the information either to
      provide effective parent education interventions or to be able to refer parents
      to effective programs.

PMID- 11326465
TI  - Flying home.
AB  - In the rapidly progressing field of critical care, the diverse delivery of such
      care seems to be reaching new "heights." In particular, aeromedical transport of
      critically ill patients involves detailed preparation for the worst possibilities
      but with expectations for the best outcomes. The following case is presented as
      testimony to the challenges of critical care transport.

PMID- 11326466
TI  - Child safety seats work!

PMID- 11326467
TI  - Nursing judgment: the key to pain assessment in critically ill children.
AB  - Pain assessment in critically ill children emphasizes the need to place expert
      nursing judgment prominently on the list of assessment strategies. The expert
      nurse is uniquely qualified to identify subtle responses to physiologic and
      environmental stimuli and to titrate analgesics and other pain relief strategies
      accordingly. While it is challenging to assess pain with limited verbal and
      behavioral cues, pain assessment is not only possible, but even more critical,
      when the available cues are subtle and can be easily overlooked or attributed to
      other causes. The question that sparked these comments reflects the passion I so
      often witness in intensive care nurses committed to eliminating pain as an
      emotional and physiological stressor for these vulnerable children. When that
      passion is empowered by evidence-based nursing judgment, children receive the
      best possible care.

PMID- 11326468
TI  - Resources for child advocacy.

PMID- 11326469
TI  - Tar wars: educating today's youth about tomorrow's health.

PMID- 11326470
TI  - Alternative medicine in rheumatology: threat or challenge?

PMID- 11326471
TI  - Risedronate increases bone mineral density and reduces the vertebral fracture
      incidence in postmenopausal women.

PMID- 11326472
TI  - Etanercept improves active polyarticular juvenile rheumatoid arthritis.

PMID- 11326473
TI  - Urinary glycosaminoglycans in patients with systemic lupus erythematosus.
AB  - OBJECTIVE: Several investigations indicate that glycosaminoglycans (GAG) are
      important components of the glomerular basement membrane (GBM) and that they play
      a remarkable role in the control of charge-selectivity in the glomerular
      capillary wall. In order to evaluate the possible use of GAG as a marker of
      glomerular disease, we evaluated urinary GAG excretion in 37 patients with
      systemic lupus erythematosus (SLE) grouped by disease activity and kidney
      involvement and in 17 healthy controls. METHODS: GAG were isolated from urine by
      using ion-exchange chromatography on DEAE Sephacel. GAG composition was
      determined by cellulose acetate electrophoresis and expressed as relative
      percentages by densitometric scanning of Alcian Blue stained strips. RESULTS:
      Total GAG levels were significantly increased only in active extra-renal SLE
      patients. Qualitative analysis of urinary GAG revealed the presence of a low
      sulphated chondroitin sulphate-protein complex (LSC-PG), whose frequency was
      higher in patients compared to controls. Moreover, inactive SLE was characterized
      by an alteration of the chondroitin sulphate/heparan sulphate ratio. CONCLUSION:
      These variations suggest the presence of an abnormal permeability of the renal
      filter in patients without other appreciable signs of kidney alteration.
      Therefore, qualitative-quantitative urinary GAG analysis could represent an
      additional diagnostic approach.

PMID- 11326474
TI  - Tumor necrosis factor-alpha and receptors for it in labial salivary glands in
      Sjogren's syndrome.
AB  - OBJECTIVE: Modulation of TNF-alpha by neutralizing antibodies, soluble receptors
      and TNFR: Fc fusion proteins are being developed for the therapeutic modulation
      of immune inflammation. It is becoming increasingly important to understand the
      state and involvement of the TNF-alpha/TNFR system in various rheumatic diseases.
      Tumor necrosis factor-alpha (TNF-alpha) affects its target cells through binding
      to two different receptors, TNFR-p55 and TNFR-p75. Mitogenic, cytostatic and
      cytotoxic effects of TNF-alpha on various cells have been reported. In Sjogren's
      syndrome (SS) focal sialadenitis leads to salivary gland destruction and loss of
      function. Although TNF-alpha is one possible mediator in these processes, nothing
      is known about the spatial distribution of TNF-alpha in relation to its
      receptors/target cells in salivary gland tissue. METHODS: Labial salivary glands
      (LSG) were obtained from 16 SS patients and 13 healthy controls and stained using
      the immunohistochemical peroxidase-anti-peroxidase (PAP) method for TNF-alpha,
      TNFR-p55 and TNFR-p75. RESULTS: TNF-alpha, TNFR-p55 and TNFR-p75 staining was
      absent, weak or relatively inextensive in controls compared to SS patients.
      Infiltrating mononuclear inflammatory cells in SS patients displayed moderate to
      strong TNF-alpha and TNFR expression. In addition, resident vascular endothelial
      cells, ductal epithelial cells and fibroblasts co-expressed TNF-alpha and TNFR.
      In contrast, acinar end piece cells did not express TNF-alpha or TNFR-p75
      although TNFR-p55 was expressed. CONCLUSION: The interrelated localization of TNF
      receptors and their ligand TNF-alpha in inflammatory and in endothelial cells
      suggests a proinflammatory role of TNF-alpha in SS. The expression of TNF-alpha
      and its receptors in fibroblasts and ductal cells may contribute to ductal
      hyperplasia and glandular fibrosis. However, in contrast to expectations, the
      cellular localization of the TNF-alpha/TNRF system argues against its role in
      acinar cell atrophy.

PMID- 11326475
TI  - Manometric assessment of impaired esophageal motor function in primary Sjogren's
      syndrome.
AB  - OBJECTIVE: To evaluate by manometry the esophageal motility changes in patients
      with primary Sjogren's syndrome (SS). METHODS: Esophageal manometry was carried
      out in 25 (F/M: 22/3) primary SS patients with systemic manifestations and in 42
      control subjects. The primary SS patients also completed a dysphagia scoring
      questionnaire and underwent whole salivary flow measurements. RESULTS: As
      compared with the controls the primary SS patients exhibited a decreased lower
      esophageal sphincter (LES) pressure (P < 0.01) and a prolongation of LES
      relaxations (P < 0.02). In the esophageal body (EB) a decreased peristaltic
      velocity (p < 0.01), an increased duration of contractions (p < 0.01) and a
      higher occurrence of simultaneous waves (p < 0.01) were detected. Since decreased
      peristaltic velocity was the most frequent motor abnormality (11/25 cases), two
      groups of patients were formed for further analysis: patients with a decreased
      (group I, n = 11) and patients with a normal (group II, n = 14) peristaltic
      velocity. The SS patients with a decreased EB propagation velocity (< or = 2.7
      cm/s, group I) displayed more significantly decreased pressures (p < 0.01) and
      more prolonged relaxation times (p < 0.05) in the LES, with higher rates of
      simultaneous contractions on dry swallows (p = 0.05) in the EB, as compared with
      those who had a normal peristaltic velocity (group II). Of the clinical
      parameters, the decreased EB peristaltic velocity was associated with a smaller
      whole saliva production both in the basal state and after stimulation.
      Furthermore, this group of patients had a significantly higher liquid requirement
      for swallowing than those who had normal peristaltic velocities (p = 0.05).
      CONCLUSIONS: Primary SS patients with systemic manifestations exhibit several
      esophageal motility abnormalities. In this study, a decreased EB peristaltic
      velocity was the most common manometric change, and showed an association with
      impaired saliva production and higher liquid requirement for swallowing, but not
      with the laboratory parameters or with the systemic manifestations of the
      disease.

PMID- 11326477
TI  - Changes in proteoglycan content of articular cartilage during avian degenerative
      joint disease.
AB  - OBJECTIVE: To determine the biochemical changes in articular cartilage
      composition associated with the development of avian degenerative joint disease
      (DJD) in ad libitum fed broiler fowl, in comparison to feed-restricted broilers
      and J-lin fowl (non-susceptible to DJD). METHODS: Articular cartilage from the
      distal tibiotarsus (DTT) was characterised up to age 180 days. Proteoglycan
      content was determined by uronic acid and sulphated glycosaminoglycan analysis,
      cellularity by assay for DNA content, and collagen content and crosslinking by
      hydroxyproline and pyridinoline analysis, respectively. RESULTS: Disease
      development was accompanied by increased hydration and proteoglycan content
      (particularly sulphated proteoglycans) and decreased cellularity, with no
      significant differences in either total collagen content or in mature collagen
      cross-linking. CONCLUSION: The biochemical features of avian DJD are similar to
      those observed in other animal models. This bipedal model is exceptional however
      since cartilage alterations occur spontaneously and in a load-dependent manner.

PMID- 11326476
TI  - Suppression of adjuvant arthritis in rats by boar seminal immunosuppressive
      fraction.
AB  - OBJECTIVE: The effect of the immunosuppressive fraction of boar seminal vesicle
      fluid (ISF) was tested on the manifestation of adjuvant arthritis (AA) in rats.
      METHODS: The inhibitory effect of ISF on mitogen-stimulated proliferation of rat
      lymphocytes was evaluated by immunoassay using bromodeoxyuridine incorporation.
      Adjuvant arthritis was induced in male Long Evans rats with Mycobacterium
      butyricum in adjuvant. ISF was administered at the time of the induction of
      arthritis. At the time of maximal manifestation of the disease, the hind paw
      swelling and thymus weight were estimated. IgM and IgG in the rat blood sera were
      quantified by sandwich ELISA. Serum corticosterone was analyzed by
      radioimmunoassay. Serum NO2-/NO3-were estimated by diazotation. Serum albumin was
      measured spectrophotometrically. The expression of IL-6 mRNA in peritoneal
      macrophages was estimated by dot-blot hybridization. RESULTS: Treatment of
      arthritic rats with ISF attenuated hind paw edema. The production of IgG
      subclasses dropped in ISF-treated AA rats. The thymus mass and serum albumin
      concentration were partially restored due to the ISF treatment. Serum
      corticosterone as well as NO2-/NO3- concentrations were reduced by the ISF
      effect. The expression of IL-6 in peritoneal macrophages was inhibited in AA rats
      after ISF treatment. CONCLUSION: ISF attenuated the manifestation of AA in rats
      and mitigated the inflammation. Immunoglobulin production was most probably
      inhibited by the decreased proliferation of B lymphocytes.

PMID- 11326478
TI  - Longitudinal study of rheumatoid arthritis patients discloses sustained elevated
      serum levels of soluble CD106 (V-CAM).
AB  - OBJECTIVE: To appreciate the evolution of serum angiogenic and/or adhesion
      molecules levels during a long term follow-up of rheumatoid arthritis (RA)
      patients. METHODS: Serum levels of 5 soluble adhesion/angiogenesis glycoproteins
      (VEGF, CD31, CD54, CD62E, CD106) were measured in Elisa in samples collected over
      6 years in a cohort of 43 RA patients with monitored clinical parameters of
      disease activity and severity. RESULTS: RA patients had significantly higher
      levels (p < 0.0001) of sCD106 (VCAM-1) than control subjects. Conversely, the
      levels of soluble VEGF, CD31, CD54 and CD62E were normal or lower than normal. No
      statistically significant time effect was noted. No effect either was noted as
      related to the therapeutic agents taken by the patients. CONCLUSION: The
      sustained elevated serum levels of sCD106 observed here imply that this molecule
      might be related to the chronicity and progression of RA.

PMID- 11326479
TI  - Prognostic factors and long-term evolution in a cohort of 133 patients with giant
      cell arteritis.
AB  - OBJECTIVE: Survival in patients with giant cell arteritis (GCA) has generally
      been found to be similar to that of the general population. The aim of our study
      was to assess outcome and survival of different subgroups of patients with GCA in
      relation to clinical, biological data or treatment modalities. METHODS: From 1977
      and 1995, 176 patients were treated in the Department of Internal Medicine for
      GCA. The patient, family or local practitioner were contacted prior to the study
      (July-October 1995). Treatment modalities and follow-up were obtained for 133
      patients. All patients (except 11) had 3 or more 1990 ACR classification criteria
      for GCA. The 11 patients with 2 criteria had a positive temporal biopsy and were
      included in the study. RESULTS: Relapse during corticosteroid tapering treatment
      was observed in 83 patients (62.4%) with a mean 1.57 relapses per patient. No
      correlation was found in age, sex, initial dose or type of steroid used (i.e.
      prednisone or prednisolone). Only a slight correlation in the initial erythrocyte
      sedimentation rate (ESR) was observed (p < 0.01, r = 0.23). In 56 patients free
      of treatment (mean treatment duration: 40 months), 27 (48%) developed a relapse
      of the disease 1 to 25 months later. No correlation was found in age, sex,
      initial dose of steroid, number of relapses during treatment, or initial ESR.
      Survival analysis was performed using the Kaplan-Meier and Mantel-Menszel methods
      for comparison of groups. At the time of the study, 41 patients had died (30.7%).
      A significant reduction of survival was found with the presence of permanent
      visual loss vs absence (p = 0.04), in patients who required more than 10 mg/d of
      glucocorticoid (p < 0.001) at 6 months treatment and in patients treated with
      prednisone (vs prednisolone) (p < 0.01). However, these factors were not
      independently associated with survival in the multivariate analysis. CONCLUSION:
      Relapse was observed in 62.4% of the patients during corticosteroid tapering
      (correlated with initial ESR). A relapse of the disease was also observed in 48%
      of patients 1 to 25 months after the end of the treatment and was associated with
      prednisolone use. Long term survival was better in patients with no initial
      ocular manifestations, in patients who took less than 10 mg/day of
      corticosteroids at 6 months of the treatment and in patients treated with
      prednisolone.

PMID- 11326480
TI  - Herbal therapies in rheumatology: the persistence of ancient medical practices.
AB  - OBJECTIVE: To determine how frequently herbal remedies are employed as
      alternative therapies in rheumatic diseases, and the historical justification for
      their use. METHODS: We conducted a survey in 250 outpatients in the rheumatology
      clinic of a teaching hospital in Mexico. We registered general demographic
      information and the previous use of herbal remedies for rheumatic conditions, how
      effective they were, and the presence of adverse effects during their use. We
      identified the herbs employed, and cross-checked them with medical texts from the
      16th through the 18th centuries on the use of herbal remedies. RESULTS: Of 250
      surveyed patients, 126 (51%) had used herbal remedies for their rheumatic
      conditions. 63% of all users reported them to be effective for the purpose they
      had been prescribed. 12% reported adverse effects, none of them life-threatening.
      Being a user had no relation with the patients' formal education. Three patients
      did not answer the survey. We were able to identify 67 plants. One third of these
      are either prescribed for rheumatic conditions in the consulted bibliography, or
      else were used for the same purpose by ancient Mexican cultures. CONCLUSION:
      Herbal remedies are frequently used for rheumatic conditions. Some of them have
      an historical antecedent for their use in rheumatic conditions. They deserve a
      cautious evaluation as adjunctive therapies in rheumatic diseases.

PMID- 11326481
TI  - Profile of Reiter's disease in Saudi Arabia.
AB  - We studied the clinical features of cases of Reiter's disease as seen in two
      tertiary care hospitals in Riyadh, Saudi Arabia, over a period of 9 years. We
      gathered 34 cases, 29 (85%) males and 5 (15%) females (M:F ratio 5.8:1). The mean
      age of onset was 29.4 (SD 6.4) years. Gastrointestinal and genitourinary
      infection were elicited in 24 patients (71%). Fever occurred in 6 patients (18%),
      fatigue in 13 (38%) and conjunctivitis in 13 (38%). Lower limb large joints were
      affected at presentation in 23 patients (68%), followed by combined presentation
      of peripheral joints and axial joints in 10 patients (30%). Sacroilitis was seen
      in 5 cases (15%). One patient had spondylitis, while enthesopathy was seen in 6
      patients (18%). Bone scintigraphy was done in 14 patients, 11 of which were
      positive at peripheral joints, while 9 showed increased uptake at the sacroiliac
      joints. HLA B27 status was tested in 15 patients, 4 (27%) of which were positive.

PMID- 11326482
TI  - Bronchiectasis in systemic sclerosis. A study using high resolution computed
      tomography.
AB  - OBJECTIVE: To detect noninvasively the presence of bronchiectasis in patients
      with systemic sclerosis (SSc), through the use of high resolution chest computed
      tomography (HRCT). METHODS: Twenty two patients with SSc, of whom 13 with diffuse
      and 9 with limited disease, besides a complete history, physical and routine
      laboratory and immunologic profile, were evaluated by pulmonary function testing
      and HRCT. The chi square test with Yates' correction, the Fisher's exact test,
      the Fisher's test (F test) and the "t" test were used for statistical analysis of
      the results. RESULTS: Eleven patients (50.0%) had decreased carbon monoxide
      diffusing lung capacity (DLCO) and, out of these, four had restrictive lung
      disease, based on a combined decrease of forced vital capacity (FVC) and total
      lung capacity (TLC). Another two patients exhibited this pattern without DLCO
      impairment. HRCT revealed a ground glass picture in 15 patients (68.2%), fibrosis
      in 9 (40.9%) (of which 5 with ground glass as well), and cylindrical
      bronchiectasis in 13 (59.1%). Bronchiectasis was more common in diffuse than in
      limited SSc, and the difference approached but did not reach the level of
      statistical significance. On the other hand, it was not correlated with either
      decreased DLCO, presence of ground glass and fibrosis, or with patients' age and
      disease duration. CONCLUSION: Although the number of patients included in our
      study is relatively small, our data, for the first time in the literature,
      indicate a significant association between scleroderma and bronchiectasis.
      Bronchiectasis should be included in the list of pulmonary manifestations of SSc,
      and SSc in the list of conditions causing bronchiectasis.

PMID- 11326483
TI  - Risk factors for infection and role of C-reactive protein in Korean patients with
      systemic lupus erythematosus.
AB  - To evaluate risk factors for infection and the role of C-reactive protein (CRP)
      in the diagnosis of infection, a retrospective case control study was performed
      among Korean systemic lupus erythematosus patients. Of 120 proven infections, 31
      episodes (25.8%) occurred in patients taking no corticosteroids (CS). The risk of
      infection was lower in patients taking low-dose CS (< 300 mg prednisolone/month)
      than no CS (odds ratio (OR) 0.36). In patients receiving high-dose CS (> 1000 mg
      prednisolone/month), however, the risk increased (OR 2.9). In patients taking no
      CS, disease activity manifested as increased SLEDAI, anemia and active urinary
      sediment, was associated with infection. The CRP was higher in the patients with
      infection than controls and the CRP levels over 50 mg/l were observed only in
      infection. These results suggest that CS have a bimodal influence on infection
      depending on dose. Disease activity is an important risk factor for infection in
      patients taking no CS. Finally, CRP levels greater than 50 mg/l suggest the
      presence of infection.

PMID- 11326484
TI  - Transverse myelitis in a patient with long-standing ankylosing spondylitis.
AB  - Ankylosing spondylitis is reported to involve not only the joints but other
      organs as well. Among these extra-articular involvements, uncommon complications
      associated with nervous system such as single root lesions, compression of the
      myelum and cauda equina syndrome have also been documented. Here we present a
      patient with long-standing ankylosing spondylitis who developed spastic
      paraparesis. Extensive study to find the cause of a spastic paraparesis failed
      and therefore led to the conclusion that this patient was suffering from
      transverse myelitis. Similar reports in the past have been attributed to an
      association with multiple sclerosis; however, we suggest that the findings
      support the diagnosis of a rare complication of ankylosing spondylitis with an
      unknown etiology.

PMID- 11326485
TI  - Scleroderma in association with the use of docetaxel (taxotere) for breast
      cancer.
AB  - The taxanes, paclitaxel (Taxol) and docetaxal (Taxotere), are a new class of anti
      microtubule agents which have shown cytotoxic activity in a number of solid
      tumours. Phase I and II trials confirm that docetaxal is highly active in the
      treatment of metastatic breast cancer. Reported toxicities of docetaxel include,
      dose limiting neutropenia, alopecia, skin reactions and fluid retention. Here we
      report the first case of rapid onset, diffuse scleroderma-like illness, which
      occurred in a 59-year-old female receiving treatment with docetaxel for locally
      invasive and advanced metastatic breast cancer.

PMID- 11326486
TI  - An uncommon association: celiac disease and dermatomyositis in adults.
AB  - We describe the case of a patient with a two-year history of adult
      dermatomyositis (DM) who developed malabsorption revealing celiac disease. Our
      observation raises the question of an association between DM and celiac disease
      as part of a continuum, suggesting that celiac disease may be included within the
      spectrum of the gastrointestinal manifestations of DM and polymyositis (PM). From
      a practical point of view, our data indicate that the diagnosis of celiac disease
      should be suspected in PM/DM patients exhibiting malabsorption syndrome. Based on
      our findings, we further emphasize that an evaluation for celiac disease,
      including anti-gliadin antibodies, anti-endomysium antibody and tissue trans
      glutaminase antibodies should be considered in PM/DM patients presenting with
      unusual and unexplained gastrointestinal features. This could lead to the early
      management of such patients, resulting in decreased morbidity (i.e., malnutrition
      and malignancy) related to misdiagnosed celiac disease.

PMID- 11326487
TI  - Fibromyalgia syndrome and serotonin.
AB  - Although disturbances in the musculoskeletal system, in the neuroendocrine system
      and in the central nervous system (CNS) have been implicated in the
      pathophysiology of fibromyalgia syndrome (FMS), the primary mechanisms underlying
      the etiopathogenesis of FMS remain elusive. It has been postulated that
      disturbances in serotonin metabolism and transmission, along with disturbances in
      several other chemical pain mediators, are present in patients with FMS. In this
      article we review published studies on the pathophysiological role of serotonin
      in FMS. Although studies that indirectly measured the function of serotonin in
      the CNS in FMS revealed some abnormalities in the metabolism and transmission of
      serotonin, the role of serotonin in the pathophysiology of syndrome remains
      inconclusive and warrants more studies.

PMID- 11326488
TI  - Systemic onset juvenile chronic arthritis, polyarticular pattern and hip
      involvement as markers for a bad prognosis.
AB  - OBJECTIVE: To explore all the common clinical and biological variables that are
      characteristic of Systemic onset Juvenile Chronic Arthritis (SoJCA) in order to
      determine which of them are suitable as predictors of a bad articular outcome
      (persistence of inflammatory symptoms and/or established limitation of the range
      of motion (ROM). MATERIAL AND METHODS: Clinical charts for 124 SoJCA patients
      were retrospectively reviewed. From them, 91 were finally included in the study
      because they had all of the clinical and biological data at disease onset
      properly recorded. All have been followed for at least 3 years since the
      beginning of the disease. Data collected at onset, and after 3 and 6 months of
      the disease included: 1) systemic symptoms; 2) joint involvement, using both the
      usual articular count and the value of an articular index (Helsinki Index = HI)
      which intentionally excludes those joints that are not uniformly recorded in
      clinical charts; and 3) biological data. HI was used to separate the patients
      into two groups. When applied 3 years after the disease onset, HI > or = 10
      represented a bad articular outcome while HI < 10 meant a good prognosis. SPSS
      for Windows 6.1 was used for both the univariate and multivariate analyses.
      RESULTS: From the multivariate logistic regression analysis, two different
      "clusters" of clinical data were found to be the best predictors of a bad
      articular outcome. A bad prognosis was linked at onset with the presence of
      generalized lymphadenopathies, age < 8 years and an HI > 6; at six months a bad
      outcome was linked with the presence of a polyarticular pattern plus hip
      involvement. CONCLUSION: Clinical parameters at the beginning of the disease were
      shown to be extremely useful in predicting the articular outcome of SoJCA.
      Therefore, they could constitute a good instrument to help clinicians tailor the
      best therapy for their patients.

PMID- 11326489
TI  - Juvenile idiopathic arthritis in multicase families.
AB  - OBJECTIVE: To characterize juvenile idiopathic arthritis (JIA) patients from
      multicase families. METHODS: The study series comprised 80 affected siblings
      belonging to 37 families. Comparisons were made with a population-based series of
      JIA patients from Finland and with a sibling series from the United States.
      RESULTS: The distribution of cases according to onset type was similar in the
      sibling and population-based series. The age at diagnosis was significantly lower
      in the sibling series (4.8 years vs 7.4 years; p < 0.001). There was more intra
      pair similarity in onset and course types in the United States series compared to
      the Finnish series and the proportion of girls was higher in the former.
      CONCLUSION: The only significant difference between familial and sporadic cases
      with JIA is an earlier onset of disease in familial cases. There is no essential
      difference in clinical features of the disease between patients in the multicase
      and sporadic groups. Differences between the Finnish and US series may be due to
      selection bias in the latter.

PMID- 11326490
TI  - Scleroderma in a child after chemotherapy for cancer.
AB  - The association of malignancy with scleroderma is very rare in childhood. A 13
      year-old girl was diagnosed as having thymic carcinoma and received systemic
      chemotherapy. She presented with symptoms of Raynaud's phenomenon 9 months after
      the cessation of chemotherapy. She also had difficulty in swallowing. Based on
      the presence of Raynaud's phenomenon, characteristic skin changes over the face
      and hands, oesophageal involvement and pulmonary restrictive defect demonstrated
      by pulmonary function tests, the diagnosis of generalised scleroderma was
      established. There was no evidence of tumor recurrence. Although she was treated
      with penicillamine and prednisolone, no significant improvement was achieved in
      her condition during the 14-month follow up.

PMID- 11326491
TI  - Fatal strongyloides hyper-infection in a patient with rheumatoid arthritis.

PMID- 11326492
TI  - Systemic, secondary amyloidosis in a patient with psoriatic arthritis.

PMID- 11326493
TI  - Systemic lupus erythematosus presenting as Kikuchi-Fujimoto disease.

PMID- 11326494
TI  - Polyarthritis following interferon alpha treatment in a patient with localized
      Wegener's granulomatosis.

PMID- 11326495
TI  - The historical record is consistent with the recent finding of parvovirus B19
      infection of bone marrow in systemic sclerosis patients.

PMID- 11326496
TI  - Muscular rheumatism following breast surgery in Denmark.

PMID- 11326497
TI  - Antibiogram-driven anti-microbial treatment for Ureaplasma urealyticum
      genitourinary infection can be effective against chronic monoarthritis.

PMID- 11326498
TI  - Streptococcal toxic shock syndrome in a patient with rheumatoid arthritis.

PMID- 11326499
TI  - Spondyloarthropathy and Turner's syndrome.

PMID- 11326501
TI  - Thrombosis of the retinal artery in a patient with Churg-Strauss syndrome.

PMID- 11326500
TI  - Femoral head osteonecrosis after topical corticosteroid therapy.

PMID- 11326502
TI  - C-reactive protein as measured by a sensitive enzyme-linked immunosorbent assay
      in patients with juvenile idiopathic arthritis.

PMID- 11326503
TI  - Bond strength of dual-cured resin cements to human teeth.
AB  - PURPOSE: This study evaluated the bond strength of four commercial resin luting
      cements to enamel and superficial dentin, using a second-generation laboratory
      composite. MATERIALS AND METHODS: Forty teeth were embedded in acrylic: 20 had
      superficial dentin exposed; 20 had enamel exposed. Each group was divided into
      four subgroups (n = 5) to be bonded with Variolink II, Dual Cement, 2-bond-2, and
      Permalute System, using an inverted, truncated cone of pre-cured Artglass that
      was placed over the resin cement with a load of 2 N for 2 seconds. Specimens were
      stored at 37 degrees C in 100% relative humidity for 24 hours before being tested
      for tensile bond strength (MPa). Data were analyzed using a two-way analysis of
      variance. Tukey-Kramer intervals for comparisons among resin cements and bonding
      substrates were calculated at a .05 significance level. RESULTS: Significant
      differences were found among resin cements. Variolink II had statistically higher
      bond strength values for both substrates than the rest of the cements evaluated.
      When bonding was to enamel, all failures were cohesive in the composite, and when
      bonding was to dentin, some adhesive failures occurred at the resin cement-dentin
      interface. Permalute System had higher bond strengths than 2-bond-2 and Dual
      Cement when bonded to enamel. CONCLUSIONS: Variolink II and Permalute had
      statistically different bond strengths to enamel and dentin. Variolink II showed
      statistically higher values for dentin bonding than the other cements. Use of
      Variolink II and Permalute resulted in statistically higher bond strengths than
      the other two cements.

PMID- 11326504
TI  - Pit and fissure sealants.

PMID- 11326505
TI  - Enamel microabrasion: a new approach.
AB  - Enamel microabrasion is a proven method of removing superficial intrinsic enamel
      discoloration defects. The method is safe, easily performed, and causes no
      discomfort for the patient. A new commercially available microabrasion system has
      been introduced by Ultradent Products Inc. In addition, a new tooth isolation
      material is available, along with a visible light-activated in-office hydrogen
      peroxide solution. This article describes these new products and documents tooth
      color correction for two young patients using this new tooth-color correction
      approach.

PMID- 11326506
TI  - Computer imaging versus conventional esthetic consultation: a prospective
      clinical study.
AB  - Computer imaging can be helpful in demonstrating to patients the potential
      outcome of esthetic dental procedures. The current clinical study assesses the
      effectiveness of computer imaging by comparing the reactions of patient and
      dentist to conventional consultations versus the use of computer imaging. The
      responses from 35 subjects show that computer imaging consultations are more
      effective in helping patients decide to accept treatment. Patient satisfaction
      was higher (93.75%) with computer consultations than with conventional methods
      (83.3%). Computer imaging consultations were easier to conduct but significantly
      (p < .05) more time consuming.

PMID- 11326507
TI  - Effect of camera angulation on adaptation of CAD/CAM restorations.
AB  - PURPOSE: A significant concern with computer-assisted design/computer-assisted
      manufacturing (CAD/CAM)-produced prostheses is the accuracy of adaptation of the
      restoration to the preparation. The objective of this study is to determine the
      effect of operator-controlled camera misalignment on restoration adaptation.
      MATERIALS AND METHODS: A CEREC 2 CAD/CAM unit (Sirona Dental Systems, Bensheim,
      Germany) was used to capture the optical impressions and machine the
      restorations. A Class I preparation was used as the standard preparation for
      optical impressions. Camera angles along the mesio-distal and buccolingual
      alignment were varied from the ideal orientation. Occlusal marginal gaps and
      sample height, width, and length were measured and compared to preparation
      dimensions. For clinical correlation, clinicians were asked to take optical
      impressions of mesio-occlusal preparations (Class II) on all four second molar
      sites, using a patient simulator. On the adjacent first molar occlusal surfaces,
      a preparation was machined such that camera angulation could be calculated from
      information taken from the optical impression. Degree of tilt and plane of tilt
      were compared to the optimum camera positions for those preparations. RESULTS:
      One-way analysis of variance and Dunnett C post hoc testing (alpha = 0.01)
      revealed little significant degradation in fit with camera angulation. Only the
      apical length fit was significantly degraded by excessive angulation. The CEREC 2
      CAD/CAM system was found to be relatively insensitive to operator-induced errors
      attributable to camera misalignments of less than 5 degrees in either the
      buccolingual or the mesiodistal plane. The average camera tilt error generated by
      clinicians for all sites was 1.98 +/- 1.17 degrees.

PMID- 11326508
TI  - Effects of different re-wetting techniques on dentin shear bond strengths.
AB  - PURPOSE: For contemporary hydrophilic resin adhesive systems, bonding to dentin
      is improved if the substrate is maintained in a hydrated state following acid
      etching. The purpose of this study was to compare the dentin shear bond strengths
      of two single-bottle adhesives (one acetone-based and one ethanol-based) applied
      under different etched-dentin conditions: dry, wet, or dry and re-wetted with
      different solutions. MATERIALS AND METHODS: Bovine incisors (N = 120) were
      mounted in acrylic, polished to 600-grit, and randomly assigned to 12 groups (n =
      10). Dentin was etched for 15 seconds using 35% phosphoric acid, rinsed, and
      either blot-dried, air-dried, or air-dried and re-wetted with different solutions
      (distilled water, Gluma Desensitizer, Aqua-Prep, and 5% glutaraldehyde in water).
      Two adhesives (Single Bond and Prime & Bond NT) were applied to each of the
      surface conditions following manufacturers' instructions. After adhesive
      application and curing, composite was applied in a No. 5 gelatin capsule and
      light-cured. Specimens were loaded in shear, using an Instron at 5 mm per minute.
      Shear bond strengths were calculated by dividing the failure load by the bonded
      surface area. Data were subjected to analysis of variance (ANOVA) and a post hoc
      Tukey test. RESULTS: Mean shear bond strengths ranged from 12.5 to 26.6 MPa for
      Single Bond and from 5.6 to 14.7 MPa for Prime & Bond NT. Significant differences
      were found in both groups of materials (p < .001). The three highest mean bond
      strengths were obtained (in order) on dentin that was re-wetted with Gluma
      Desensitizer, re-wetted with Aqua-Prep, or never dried. Differences between these
      surface conditions were not statistically significant for either material.

PMID- 11326510
TI  - Smile on! The MDA heads in a new direction.

PMID- 11326509
TI  - Effect of alcoholic and low-pH soft drinks on fluoride release from compomer.
AB  - PURPOSE: The purpose of this study was to evaluate the amount of fluoride
      released from compomer restorative materials after immersion in various media.
      MATERIALS AND METHODS: In this test, four materials were used: three compomers
      (Dyract, Dentsply, Konstanz, Germany; Compoglass, Vivadent, Schaan, Principality
      of Liechtenstein; and Xeno, Sankins, Tochigi, Japan) and one resin-modified glass
      ionomer cement (Fuji II LC, GC, Tokyo, Japan). There were four test solutions:
      one alcoholic (whiskey), two low-pH drinks (Coca-Cola, orange juice), and one
      deionized water. Over a period of 60 days, the tested specimens were immersed in
      the test solution for 3 hours every day, then kept in deionized water. The
      fluoride released was detected by using a fluoride ion selective electrode
      connected to a microprocessor ion analyzer. The fluoride ion concentration (ppm)
      of the test solutions and deionized water was recorded after 1, 2, 3, 4, 7, 30,
      and 60 days. Electron probe microanalysis was used for surface analysis of the
      fluoride released. RESULTS: When immersed in low-pH soft drinks, compomer showed
      a significantly higher fluoride release than when immersed in deionized water (p
      < .0001). For specimens immersed in Coca-Cola, the fluoride release levels
      (microgram/cm2, mean +/- SD) at 1, 7, and 60 days for Dyract (91.6 +/- 1.8, 39.3
      +/- 3.1, 10.5 +/- 0.9), Compoglass (129.5 +/- 0.9, 66.5 +/- 2.7, 19.0 +/- 0.3),
      Fuji II LC (147.0 +/- 4.2, 50.8 +/- 3.1, 27.6 +/- 3.0), and Xeno (73.6 +/- 3.2,
      27.3 +/- 2.1, 6.6 +/- 0.6) demonstrated the trend of significantly lower releases
      with time in water solution. Over a 60-day period, materials immersed in 100%
      orange juice released the highest amount of fluoride, which could be attributable
      to the erosive effect of the medium. Materials immersed in deionized water
      released the least amount of fluoride. Among the tested compomers, Compoglass
      released the most fluoride.

PMID- 11326511
TI  - Bills would require timely payment by insurers.

PMID- 11326512
TI  - Premises liability of a dentist owner.

PMID- 11326513
TI  - Interview: New MDA president Dr. Gary Asano. Interview by Michael Maihofer.

PMID- 11326515
TI  - Embracing technology: computers aren't just for billing anymore.

PMID- 11326514
TI  - UDM dental school expands dental outreach to the Dominican Republic.

PMID- 11326516
TI  - Achieving consensus.

PMID- 11326517
TI  - Building the multi-generation dental team.

PMID- 11326518
TI  - Occlusion: what it is and what it is not.
AB  - Dental occlusion is much more than the physical contact of the biting surfaces of
      opposing teeth or their replacements. Occlusion is more comprehensively defined
      biologically as the coordinated functional interaction between the various cell
      populations forming the masticatory system as they differentiate, model, remodel,
      fail, and repair. Morphologic variations are very common and represent the norm.
      Even though the occlusal or musculoskeletal relationship may not meet the
      definition of the clinician's concept of an optimum or ideal occlusion, it must
      be appreciated that for that particular patient, the tissues of the masticatory
      system may have developed a stable, functional, healthy, and comfortable
      equilibrium. However, when the functional equilibrium is perturbed or when the
      occlusion is being re-established, specific treatment criteria are as important
      today, if not more important with the rapid growth of implant placements, as ever
      before. Treatment of the occlusion should be considered on an individual basis
      based on the specific physiologic needs of the various tissue systems within the
      masticatory system rather than on a preconceived, stereotyped or universal basis.
      It has long been established and recently proven that proper management of the
      occlusion is directly correlated to the successful treatment and maintenance of
      the teeth and, at times, the supporting tissues. On the other hand, it has not,
      to date, been scientifically proven that occlusion is directly correlated to the
      musculoskeletal disorders that affect the jaw (temporomandibular joint or
      masticatory muscle disorders).

PMID- 11326519
TI  - Occlusal considerations in determining treatment prognosis.
AB  - To function in occlusal harmony, the masticatory apparatus--composed of the teeth
      and its supporting structures, temporomandibular joints, and associated
      neuromusculoskeletal structures--must operate in an integrated and dynamic
      manner. Loss of integrated function, or of homeostasis in response to functional
      demand, may generate problems in occlusion. In health, adaptive changes occur
      with the teeth and periodontium in response to functional occlusal forces. With
      periodontal and endodontic disease, this adaptive capacity diminishes. The
      ability to foresee how these changes may influence dental treatment is important
      in the art of determining treatment prognosis.

PMID- 11326520
TI  - Occlusal considerations for implant restorations in the partially edentulous
      patient.
AB  - The type and frequency of complications associated with dental implants has
      changed during the past decade. As more-successful rates of osseointegration have
      resulted from improved surgical protocols and materials, the major complications
      have become restorative-related rather than surgery-related. Recent studies
      indicate that restorative complications with implant-retained restorations occur
      at rates of 10 percent to 77 percent over a three-year period. Many of the
      restorative complications can be minimized with careful treatment planning and
      coordination of care. However, because implants lack the stress release
      associated with a periodontal ligament, impact loading to restorative materials
      and the crestal bone remains potentially more damaging with implant-supported
      restorations. This article discusses the biomechanical implications of implant
      restorations and outlines occlusal considerations designed to decrease
      restorative complications.

PMID- 11326521
TI  - Occlusion: an orthodontic perspective.
AB  - In recent years, orthodontists have examined their concepts of occlusion. In
      current literature, at professional meetings, and in continuing education
      courses, one hears an ongoing discussion of condylar position and mandibular
      border movements in relation to occlusion. There is a wide variation in opinion
      as to whether dental occlusion and TMJ function are interdependent. The authors
      have adopted a dynamic concept of dental function to replace the traditional
      static view of molar relationship and incisor overlap. This article discusses how
      occlusion has evolved in orthodontics and reviews Andrews' six keys to ideal
      static occlusion, the goals of ideal dynamic occlusion, and the six signs of
      developing malocclusions. The authors also review the literature on the
      relationship between orthodontics, occlusion, and TMD.

PMID- 11326522
TI  - A practical guide to occlusal management for the general practitioner.
AB  - The general dentist has a unique role as the gatekeeper of dental care. In this
      role, the generalist is called upon to be the primary diagnostician and is
      charged with the responsibility for triaging patients. Classification systems
      devised by many of the dental specialties are valuable tools for the diagnosis of
      diseases and conditions specific to the specialty, but no classifications have
      been directed to the general dentist. This paper describes a system being used at
      the University of California at San Francisco School of Dentistry that enables
      the general dentist to classify a patient's stomatognathic system as either
      physiologic or nonphysiologic and then guides the clinician toward appropriate
      treatment decisions.

PMID- 11326523
TI  - "Pouring wrongs": MDA discourages pop deals.

PMID- 11326524
TI  - An interview with U.S. Sen. Spencer Abraham.

PMID- 11326525
TI  - An interview with U.S. Rep. Debbie Stabenow.

PMID- 11326526
TI  - Dentin bonding agents and resin cements--current status.
AB  - Contemporary restorative dentistry is a rapidly evolving science which challenges
      the progressive clinician with a plethora of "new and improved" products. Sound
      product choices should be couched in the prudent consideration of well conducted
      in vitro and in vivo product research. This review shall list the most recent
      product developments in dentin bonding agents (fifth generation agents), resin
      containing dental cements and the newest generation of dental cements i.e., resin
      ionomer dental cements.

PMID- 11326527
TI  - History, development and clinical success of porcelain inlays.
AB  - The drive for alternative to amalgam as a restorative material is led by concerns
      about the safety of mercury within amalgam and also by aesthetic demands from
      patients. Early attempts to address these issues produced disappointing results
      in terms of performance from directly-placed resin composites in posterior teeth.
      While directly-placed posterior restorative materials have improved in recent
      years the indirect constructed inlay may more readily meet the functional
      requirements of premolar/molar teeth. This article seeks to review the history,
      development and clinical success of porcelain when used as an inlay material. A
      case is included to demonstrate the clinical application of this aesthetic
      technique and the author's personal recommendations.

PMID- 11326528
TI  - Recent dental attendance and levels of untreated caries in a sample of 11-12 year
      old children in Northern Ireland.
AB  - The object of the present study was to determine the relationship between dental
      attendance and the levels of untreated caries in a sample of 11-12 year old
      pupils attending first form of second level schools in the South Belfast area of
      Northern Ireland. A sample of 199 first form pupils attending second level
      schools in the area was obtained. The diagnosis of caries depended mainly on
      visual evidence following removal of debris and moisture. Blunted probes were
      used to confirm or reject doubtful lesions and no radiographs were taken. Details
      of parental employment status were obtained by a questionnaire to the parents.
      The data were entered on to an N.C.S.S. data analysis system for stepwise
      regression and analysis of variance. Overall there was a significant difference
      in the untreated caries status of those with different attendance patterns, the
      major difference being that a much higher proportion of those who had not
      attended within the previous 12 months had active caries. Almost half of the
      children had attended in the previous six months and only 16 (8 per cent) had not
      attended in the previous 12 months. Independent analysis indicated that parental
      employment status was significantly related to the level of untreated caries (p >
      or = 0.05). Independent variables entered in the stepwise regression were
      attendance, employment status and DMFT. The strongest predictors of untreated
      caries were previous caries experience and period since dental attendance, while
      employment status was a significant but weaker factor in the analysis. These
      findings may be relevant when planning the frequency of school dental screenings
      and managing the frequency of dental recalls and examinations.

PMID- 11326530
TI  - Letting go.

PMID- 11326529
TI  - An update of adverse drug reactions of relevance to general dental practice.

PMID- 11326531
TI  - Bug hunt may turn up keys to periodontal disease.

PMID- 11326532
TI  - Responsible use of antimicrobials in periodontics.
AB  - New products and treatment modalities for the management of periodontal disease
      continue to offer the clinician a large number of choices, many of which involve
      antimicrobials. Specific pathogenic bacteria play a central role in the etiology
      and pathogenesis of destructive periodontal disease. Under suitable conditions,
      periodontal pathogens colonize the subgingival environment and are incorporated
      into a tenacious biofilm. Successful prevention and treatment of periodontitis is
      contingent upon effective control of the periodontopathic bacteria. This is
      accomplished by professional treatment of diseased periodontal sites and patient
      performed plaque control. Attention to community factors, such as water
      contamination and bacterial transmission among family members, facilitates
      preventive measures and early treatment for the entire family. Subgingival
      mechanical debridement, with or without surgery, constitutes the basic means of
      disrupting the subgingival biofilm and controlling pathogens. Appropriate
      antimicrobial agents that can be administered systemically (antibiotics) or via
      local delivery (povidone-iodine) may enhance eradication or marked suppression of
      subgingival pathogens. Microbiological testing may aid the clinician in the
      selection of the most effective antimicrobial agent or combination of agents.
      Understanding the benefits and limitations of antibiotics and antiseptics will
      optimize their usefulness in combating periodontal infections.

PMID- 11326533
TI  - The focal infection theory: appraisal and reappraisal.
AB  - This paper discusses the past, present, and future of the focal infection theory
      of disease. A focal infection is a localized or general infection caused by the
      dissemination of microorganisms or toxic products from a focus of infection. The
      resurgence of the focal infection theory of disease has been greeted with great
      enthusiasm in some quarters; however, the present evidence for the relationship
      of oral microorganisms and systemic disease is very limited due not only to a
      dearth of prospective studies and a complete lack of interventional studies but
      also to very significant methodological difficulties associated with the clinical
      studies that have been performed.

PMID- 11326534
TI  - A guide to evaluating epidemiological studies.
AB  - Epidemiological studies that fail to follow established principles can lead to or
      promote false assumptions. Attention to the principles of epidemiological studies
      and avoidance of extrapolation beyond the data can remove much of the confusion
      that presently exists among the health professions and general public. This
      article offers guidelines to evaluating epidemiological studies.

PMID- 11326535
TI  - Oral microorganisms and cardiovascular disease.
AB  - The list of etiological factors for cardiovascular disease is long, complicated,
      intertwined, and yet to be completed. This paper will evaluate the current
      evidence for the pathogenic role of certain microorganisms, including those of
      the oral cavity, in the etiology of cardiovascular disease.

PMID- 11326536
TI  - Global antibiotic resistance and its impact on the dental community.
AB  - There is significant evidence that the global problem of microbial resistance to
      antibiotics has reached the dental community both in our practices and our family
      lives. This paper will present a global overview of microbial resistance, discuss
      how this problem directly affects the dental community, and show what we can do
      to change the situation, both as concerned citizens and as dental health care
      practitioners.

PMID- 11326537
TI  - The effects of rhBMP-2 on human osteosarcoma cells and human gingival fibroblasts
      in vitro.
AB  - Certain cells of the periodontium are necessary for the regeneration of tissues
      that are destroyed as a result of periodontal disease. There has been debate
      regarding which cells are the primary participants in periodontal regeneration.
      It is a well-known fact that osteoblasts are essential in new bone formation, but
      controversy surrounds the role that gingival fibroblasts may play in the
      regeneration of the hard tissues of the periodontium. If gingival fibroblasts
      could contribute to the regeneration of these tissues, they might provide an
      additional source of progenitor cells. The bone morphogenetic proteins are potent
      stimulators of cell differentiation and have been shown to induce new bone
      formation in many experimental models. This project investigated the ability of
      recombinant human bone morphogenetic protein-2 (rhBMP-2) to (1) enhance the
      production of markers of osteoblastlike cells (osteocalcin and mineralization in
      culture) in human osteosarcoma cells (MG63) and to (2) induce the expression of
      an osteoblast phenotype in cultured human gingival fibroblasts (HGFs). MG63 cells
      and pooled HGFs were exposed to varying concentrations of rhBMP-2 for 24, 48, and
      72 hours after 9 days in culture, and osteocalcin levels were measured by enzyme
      immunosorbent assay in the cell supernatants. In addition, the cells were exposed
      to rhBMP-2 for 72 hours after 18 days in culture, and mineralization was
      determined by the Von Kossa stain. The rhBMP-2 had an inhibitory effect on both
      osteocalcin production and mineralization (p < 0.05) in MG63 cells compared with
      untreated controls. In addition, increasing doses of rhBMP-2 inhibited both
      osteocalcin and mineralization in HGF cells. These results suggest that HGFs can
      express an osteoblastic phenotype when exposed to rhBMP-2; however, rhBMP-2 has
      inhibitory effects at higher rhBMP-2 doses in both cell types and may, in fact,
      be inhibitory to MG63 cells.

PMID- 11326538
TI  - Connexin-43 expression in oral-derived human osteoblasts after transforming
      growth factor-beta and prostaglandin E2 exposure.
AB  - Dental implant placement stimulates a response in the supporting tissue; the
      response involves bone remodeling and release of wound-healing factors, including
      cytokines. Important factors such as transforming growth factor-beta (TGF-beta),
      which promotes matrix synthesis, and prostaglandin E2 (PGE2), a mediator of
      inflammation, have the potential to alter the communication between bone cells
      and interfere with implant site healing. Cells responsible for the formation of
      bone are interconnected to form a multicellular network. Cell-to-cell
      communication in this network occurs in part via gap junctions. In bone cells,
      the predominant gap junction protein is connexin-43. TGF-beta is a growth
      modulator produced by osteoblasts and released from the matrix in response to
      resorption and may influence the progression of periodontal disease. TGF-beta
      also promotes the synthesis of extracellular matrix proteins such as collagen,
      fibronectin, and adhesion molecules. PGE2 is a mediator of inflammation produced
      in response to periodontal pathogens. PGE2 levels in the gingival sulcular fluid
      have been correlated with attachment loss and bone resorption. The relationship
      between these factors and connexin-43 is unclear. Oral-derived (alveolar) bone
      was used because the phenotype of bone can differ between species and between
      different sites in the body. For our studies, explants of human osteoblasts were
      cultured on eight well plates and characterized by their expression of
      osteocalcin, osteonectin, alkaline phosphatase, type 1 collagen, and connexin-43.
      Cells were grown to near confluence on 12 well plates in 20% fetal bovine serum
      (FBS) Dulbecco modified Eagle medium (DMEM) and then cultured for 24 hours in
      0.5% FBS DMEM before exposure to either 1, 5, or 10 ng/mL of TGF-beta in serum
      free DMEM for 12 or 24 hours or to 20, 80, or 300 ng/mL of PGE2 in serum-free
      DMEM for 12 or 24 hours. After incubation, cells were removed from plates by
      scraping and assayed for connexin-43 protein, first by Western blot to confirm
      the specificity of the anti-connexin-43 antibody and then by slot blot analysis
      for quantitative comparison of connexin-43 expression. Our studies showed no
      significant changes in connexin-43 expression in response to either factor. These
      studies suggest that exogenous TGF-beta and PGE2 do not alter connexin-43
      expression.

PMID- 11326539
TI  - Mini-dental implant insertion with the auto-advance technique for ongoing
      applications.
AB  - The clinical and histological results of two cases demonstrating retrieved Sendax
      mini-dental implants in two different patients is the focus of this report. The
      mini-dental implants were inserted using the auto-advance technique and loaded
      immediately. The implants were retrieved at 4 months following insertion and at 5
      months following insertion and were prepared and reviewed histologically.
      Clinically, the implants had no mobility, with no apparent exudate or bleeding
      upon probing, prior to removal. At the time explant procedures were performed,
      the mini-dental implants had provided immediate support for prostheses during the
      integration of traditional root-form endosteal implants. Upon explantation, the
      mini-dental implants were in a state of health and functioning in their intended
      purpose. Histologically, the bone appeared to be integrated to the surface of the
      implant at the light microscope level, and the bone appeared to be relatively
      mature and healthy in the areas observed, more so than one would expect in this
      amount of time from insertion of mini-dental implants with immediate loading. A
      discussion of the purposes and technique used for insertion and removal of these
      mini-dental implants is discussed. This is the first human histological report on
      the auto-advance technique with immediate loading of mini-dental implants,
      demonstrating feasibility in ongoing applications.

PMID- 11326540
TI  - Platelet-rich plasma application in sinus graft surgery: Part I--Background and
      processing techniques.
AB  - The uses of cytokine growth factors in soft tissue applications has been reported
      on. The scientific background and various processing techniques to prepare the
      autologous materials are reviewed here. An ongoing research project to study
      grafting of the maxillary sinus for bone regeneration and implant site
      preparation with the growth factor Platelet Rich Plasma is outlined.

PMID- 11326541
TI  - Autogenous bone ridge augmentation using the mandibular symphysis as a donor.
AB  - Potential host sites often present less than optimal dimensions or quality than
      are required for implant placement. This paper emphasizes a variety of surgical
      technique designed to optimize these areas. There are a number of anatomic sites
      available to serve as donors for autogenous bone grafting. They include the
      tibial plateau, the calvarium, the mandibular rami, the iliac crests and the
      symphysis of the mandible. Although each has the potential of presenting risks,
      the symphysis serves a singularly beneficial source. The techniques of harvesting
      bone, and utilizing it for a variety of grafting procedures is described, the
      benefits of such utilization are emphasized and the risks of such operations are
      reviewed.

PMID- 11326542
TI  - Light microscopic and scanning electron microscopic retrieval analyses of
      implanted biomaterials retrieved from humans and experimental animals.
AB  - This paper reports analysis obtained from 200 implant cases retrieved from humans
      and submitted to the American Academy of Implant Dentistry Research Foundation,
      Medical College of Georgia implant retrieval center. The samples that were not
      decalcified were embedded in polymethylmethacrylate and examined with scanning
      electron microscopy and routine light, polarized, or Nomarski microscopy. Cases
      included both orthopedic and dental implants, as well as entire mandibles and
      portions of maxillae obtained at autopsy. A significant number of submitted
      implants had substantial amounts of adhered bone, which permitted evaluation of
      human bone remodeling to osseointegrated implants. These implants failed because
      of implant fracture. As was observed with animal studies, healthy bone supported
      these implants, with the bone containing an interdigitating canaliculi network
      that provided communication between interfacial osteocytes and osteocytes deeper
      within the remodeled osteonal and trabecular bone. Early dental implants
      containing a coating of beads showed a connective tissue interface, which
      corresponded to the bead surface of specific orthopedic implants that underwent
      some degree of micromovement. This is in contrast with the excellent response
      reported for successful contemporary beaded implants. Significant numbers of
      osseointegrated fractured hydroxyapatite (HA)-coated dental implants demonstrated
      the adequate serviceability of these implants before biomaterial fracture. In
      contrast, the HA coating was dissociated from retrieved orthopedic implants,
      leading to extensive cup loosening and case failure. This study, therefore,
      underscores the need for evaluation of failed human dental and orthopedic
      implants. Correlations can be drawn between human retrieval and experimental
      animal studies.

PMID- 11326543
TI  - [Corticosteroid receptor and stress].
AB  - Adrenal corticosteroids readily enter the brain and exert markedly diverse
      effects, such as stress response of the target neural cells. These effects are
      regulated via two receptor systems, the mineralocorticoid receptor (MR; type I
      corticosteroid receptor) and the glucocorticoid receptor (GR; type II
      corticosteroid receptor), both of which are ligand-dependent transcription
      factors. MR is localized mainly in the hippocampus, and GR is distributed
      throughout the brain. MR and GR, however, are highly colocalized in the
      hippocampus, which is a target of the stress hormone and an especially plastic
      and vulnerable region of the brain. MR has a high affinity for
      corticosterone/cortisol, a common endogenous ligand for MR and GR, and is
      extensively bound at low levels of circulating corticosterone/cortisol. GR has a
      lower affinity and is extensively bound at high levels of circulating
      corticosterone/cortisol. These findings suggest that MR plays major roles under
      physiological conditions, whereas GR is mainly effective at high concentrations
      of corticosterone/cortisol, such as stressful conditions. The interactions of MR
      and GR in the hippocampal regions could be important for regulating stress
      response in the brain.

PMID- 11326544
TI  - [The role of calcineurin on the induction of synaptic plasticity].
AB  - Calcineurin is ubiquitously distributed phosphatase in the central nervous
      system. It has various functions, such as modulating channel properties,
      suppressing transmitter release, and activating transcript factors. Recently the
      critical role of calcineurin on synaptic plasticity, especially long-term
      depression, was reported, although the precise mechanism underlying LTD induction
      is still being debated. Calcineurin, activated by the Ca2+ influx mainly through
      the NMDA channel and calmodulin, dephosphorylates inhibitor-1, which suppresses
      PP1 activity. Thus the activation of calcineurin enhances PP1, resulting in
      facilitating the process leading to LTD induction. The activation of calcineurin
      modifies the threshold of LTP induction. A recent interesting finding is the
      gating mechanism from the early phase of LTP to the late phase of LTP by
      calcineurin activity, a process regulated by cAMP. We have reported a new type of
      LTD, which is suppressed by calcineurin that is dependent on group 2 mGluR
      receptor activity. According to the result using whole cell study with a patch
      pipette, including FK-506, an antagonist of calcineurin, the induction site of
      this LTD is presynaptic, which defers from conventional LTD. We have also
      discussed the involvement of murine protein tyrosine phosphatase (MPTP) in LTD
      induction in the hippocampal CA1 region by using an MPTP delta knockout mouse.

PMID- 11326545
TI  - [Proteinkinase B/Akt].
AB  - Proteinkinase B/Akt, which was identified in 1991, is a serine/threonine kinase
      that becomes activated at two residues, Thr308 and Ser473. Activated
      proteinkinase B/Akt activates glycogen synthesis, protein synthesis, and most
      important, the survival and proliferation of cells. It was recently reported that
      mutant preseniline-1 downregulates proteinkinase B/Akt and that lithium treatment
      changes proteinkinase B/Akt activity. Proteinkinase B/Akt thus seems important
      from a psychiatric point of view.

PMID- 11326546
TI  - [BMAL1 and circadian rhythm].
AB  - hBmal1 cDNA has been cloned from a human brain cDNA library and revealed that the
      cDNA encoded a novel bHLH-PAS transcription factor. The rBmal1 mRNA expression
      was found not only at high levels in the suprachiasmatic nuclei (SCN), but also
      in the pyriform cortex, hippocampus, and cerebellum. Furthermore, this expression
      was found in the eyes, pineal body, and peripheral organs, such as the muscle,
      liver, and heart. Bmal1 mRNA levels reveal a circadian rhythm in the rat SCN,
      with the highest expression levels at ZT18. The yeast two-hybrid screening have
      demonstrated that CLOCK forms a heterodimer with BMAL1. CLOCK. BMAL1 heterodimer
      functions as a positive transcription factor through binding to the E-box in the
      promoter region of the mPer1. Nuclear translocation is promoted by dimerization
      among PERs, or between PERs and CRYs, and the complexes inhibit the transcription
      of their own genes. This feedback loop is used in the clock output system driving
      the transcription of arginine vasopressin peptide and serotonin N-acetyl
      transferase by binding the CLOCK-BMAL1 dimer to an E-box in their promoters.

PMID- 11326547
TI  - [Triplet repeat disease from the aspect of psychiatric disease].
AB  - Since 1991, about 20 triplet repeat expansion disorders have been reported. They
      are clinically characterized by anticipation, worsening severity or earlier age
      at the onset with each succeeding generation, and imprinting, a process whereby
      specific genes are differentially, marked during parental gametogenesis,
      resulting in their differential expression. The anticipation in psychoses was
      pointed out in the 19th century, but it was ignored because no one knew the
      mechanism at that time. The discovery of triplet repeat expansion diseases has
      reawakened interest in anticipation in psychiatric diseases. Anticipation has
      been confirmed in schizophrenia, mood disorders, and anxiety disorders. Molecular
      approaches have been taken to reveal the involvement of a triplet repeat
      expansion mechanism in psychoses. Most efforts have been made for CAG-type
      trinucleotide repeats. So far, most results did not support a trinucleotide
      repeat expansion mechanism also in psychoses. One plausable explanation for the
      "false positive" result is the presence of CAG trinucleotide repeats, which are
      highly polymorphic but not associated with an obvious abnormal phenotype. The
      screening for triplet repeats besides those of the CAG type remain to be
      performed.

PMID- 11326548
TI  - Caffeine as a model drug of dependence: recent developments in understanding
      caffeine withdrawal, the caffeine dependence syndrome, and caffeine negative
      reinforcement.
AB  - Caffeine is an excellent model compound for understanding drugs of
      abuse/dependence. The results of self-administration and choice studies in humans
      clearly demonstrate the reinforcing effects of low and moderate doses of
      caffeine. Caffeine reinforcement has been demonstrated in about 45% of normal
      subjects with histories of moderate and heavy caffeine use. Recent studies
      provide compelling evidence that caffeine physical dependence potentiates the
      reinforcing effects of caffeine through the mechanism of withdrawal symptom
      avoidance. Tolerance to the subjective and sleep-disrupting effects of caffeine
      in humans has been demonstrated. Physical dependence as reflected in a withdrawal
      syndrome in humans has been repeatedly demonstrated in adults and recently
      demonstrated in children. Withdrawal severity is an increasing function of
      caffeine maintenance dose, with withdrawal occurring at doses as low as 100 mg
      per day. Increased cerebral blood flow may be the physiological mechanism for
      caffeine withdrawal headache. Case studies in adults and adolescents clearly
      demonstrate that some individuals meet DSM-IV diagnostic criteria for a substance
      dependence syndrome on caffeine, including feeling compelled to continue caffeine
      use despite desires and recommendations to the contrary. Survey data suggest that
      9% to 30% percent of caffeine consumers may be caffeine dependent according to
      DSM-IV criteria.

PMID- 11326550
TI  - [Recent legislative measures related to narcotic control].

PMID- 11326549
TI  - [Comparison of clinical characteristics of dependence on nicotine, alcohol,
      stimulants, organic solvents, and tranquilizers].

PMID- 11326551
TI  - [Current status of drug abuse by children at facilities to support their
      independence and measures to protect and educate them].

PMID- 11326552
TI  - [Treatment of substance dependence--at a public psychiatric hospital].

PMID- 11326553
TI  - [Current status and prognosis of organic solvent-related disorders treated at our
      hospital].

PMID- 11326554
TI  - [Substance dependence and in-house intensive introspective therapy--indication of
      the latter and innovation to improve its efficacy].

PMID- 11326555
TI  - Persistent high signal on diffusion-weighted MRI in the late stages of small
      cortical and lacunar ischaemic lesions.
AB  - Diffusion-weighted imaging (DWI) is very sensitive to early brain infarcts.
      However, the late stages have been insufficiently studied. Infarcts in small
      vessel disease are often multiple and of different ages, and differentiation
      between new and old lesions might be difficult. We have therefore studied the
      change with time in DWI of small (< 3 ml) ischaemic lesions. We imaged 21
      patients with an acute lacunar syndrome and a lesion visible on early DWI. They
      all had three MRI examinations 12-58 h (early), 7-16 and 54-144 days after the
      onset of stroke; 10 patients with high DWI signal on the third examination had a
      fourth examination 12-28 months after the stroke. MRI was performed at 1.5 T,
      using echo-planar DWI with 7 b-values from 0 to 1200 x 10(6) s/m2 and
      conventional T2-weighted imaging. After 7-16 days 18 of 21 lesions gave high
      signal on DWI, and 12/16 measurable lesions had a decreased apparent diffusion
      coefficient (ADC). After 54-144 days ten lesions still gave high DWI signal and
      two still had an ADC below normal. On the fourth examination there was no
      remaining high DWI signal and all ADC were higher than normal.

PMID- 11326557
TI  - FLAIR imaging in the follow-up of low-grade gliomas: time to dispense with the
      dual-echo?
AB  - Fluid-attenuated inversion-recovery (FLAIR) imaging has established its utility
      in neuroimaging. We propose this imaging sequence as a replacement for proton
      density (PD) and T2-weighted spin-echo sequences in the follow-up of low-grade
      glioma. 26 MRI examinations of 18 patients with such tumours were reviewed by
      three neuroradiologists and a neurosurgeon. FLAIR was found to be superior for
      appreciation of the lesion (91% of studies) and for demonstration of its margin
      (92%). FLAIR was also better at showing different tumour components, particularly
      in regions difficult to demonstrate in some planes, such as the vertex in axial
      imaging. The sequence also defines the postoperative cavity, shows the least
      amount of susceptibility effect associated with surgical clips, and demonstrates
      local spread (to white matter tracts, subependymal and capsular) more distinctly.
      We conclude that FLAIR can replace PD and T2-weighted spin-echo imaging in
      radiological follow-up of low-grade glioma.

PMID- 11326556
TI  - Detection of optic nerve atrophy following a single episode of unilateral optic
      neuritis by MRI using a fat-saturated short-echo fast FLAIR sequence.
AB  - We describe an MRI technique for quantifying optic nerve atrophy resulting from a
      single episode of unilateral optic neuritis. We imaged 17 patients, with a median
      time since onset of optic neuritis of 21 months (range 3-81 months), using a
      coronal-oblique fat-saturated short-echo fast fluid-attenuated inversion-recovery
      (sTE fFLAIR) sequence. The mean cross-sectional area of the intraorbital portion
      of the optic nerves was calculated by a blinded observer from five consecutive 3
      mm slices from the orbital apex forwards using a semiautomated contouring
      technique and compared with data from 16 controls. The mean optic nerve area was
      11.2 mm2 in the affected eye of the patients, 12.9 mm2 in the contralateral eye
      (P = 0.006 compared to the affected eye) and 12.8 mm2 in controls (P = 0.03
      compared to the affected eyes). There was a significant negative correlation
      between disease duration and the size of the affected optic nerve (r = -0.59, P =
      0.012). The measurement coefficient of variation was 4.8%. The sTE fFLAIR
      sequence enables measurement of optic nerve area with sufficient reproducibility
      to show optic nerve atrophy following a single episode of unilateral optic
      neuritis. The correlation of increasing optic nerve atrophy with disease duration
      would be consistent with ongoing axonal loss in a persistently demyelinated
      lesion, or Wallerian degeneration following axonal damage during the acute
      inflammatory phase.

PMID- 11326558
TI  - Change in signal intensity on MRI of fat in the head of markedly emaciated
      patients.
AB  - The amount of fat in various parts of the body decreases in emaciated patients,
      but responds differently to disease processes. The order of disappearance of fat
      in various parts of the head has rarely been studied with MRI. We imaged ten
      patients with anorexia nervosa and one cachectic patient with a psychiatric
      disorder with a 1.5 T imager. Signal intensities of bone marrow of the skull,
      subcutaneous tissue, and orbits were assessed on T1- and T2-weighted images, and
      correlated with the body mass index (BMI) and haemoglobin concentration (Hb). On
      T1-weighted images, five patients (BMI 15.6-17.8 kg/m2, mean 16.6 kg/m2; Hb 10.1
      14.2 g/dl, mean 13.8 g/dl) showed the normal pattern of fat. One (BMI 13.6 kg/m2,
      Hb 10.4 g/dl) lost the high signal of bone marrow, but high signal of
      subcutaneous tissue and the orbits was preserved. High signal from bone marrow
      and subcutaneous tissue disappeared in three patients (BMI 11.5-13.5 kg/m2, mean
      12.5 kg/m2; Hb 7.9-9.7 g/dl, mean 8.7 g/dl), but orbital high signal was
      preserved. The remaining two patients (BMI 9.3 and 13.5 kg/m2, mean 11.5 kg/m2;
      Hb 7.6 and 8.9 g/dl, mean 8.3 g/dl) showed complete loss of high signal from fat
      in the head. The order of disappearance of fat (bone marrow, subcutaneous fat,
      then orbits) correlated with both BMI and Hb. Atrophy of bone marrow was
      demonstrated on T2-weighted images in five patients with BMI 13.5 kg/m2 or less,
      and Hb 9.7 g/dl or less.

PMID- 11326559
TI  - Anatomic relationship between arachnoid granulations in the transverse sinus and
      the termination of the vein of Labbe: an angiographic study.
AB  - We studied the anatomic relationship between arachnoid granulations in the
      transverse sinus and the termination of the vein of Labbe in 57 consecutive
      angiograms. Patients with pathology in intracranial venous structures or with
      inadequate image quality of the venous system were excluded. Arachnoid
      granulations were found in 12 of the 57 patients (21.1%), always at the junction
      of the vein of Labbe and the transverse sinus; the vein of Labbe was present in
      55 patients (96.5%), most often without associated arachnoid granulations; the
      latter, however, were not observed in the absence of a vein of Labbe. This study
      confirms the close, constant anatomic relationship between arachnoid granulations
      in the transverse sinus and the termination of the vein of Labbe. This
      observation may help to differentiate arachnoid granulations from pathologic
      conditions involving the transverse sinus such as dural sinus thrombosis. The
      constant character of this relationship suggests a developmental role of afferent
      veins in the formation of arachnoid granulations.

PMID- 11326560
TI  - Sigmoid and transverse sinus thrombosis after closed head injury presenting with
      unilateral hearing loss.
AB  - Sinus thrombosis has rarely been associated with closed head injury; more often,
      thrombosis of the sigmoid or transverse sinus is caused by otogenic inflammations
      or tumours, or occurs during pregnancy. Symptoms are frequently vague, while
      untreated thrombus progression may be fatal due to venous congestion and
      infarction. We report a 32-year-old man presenting with right hearing loss,
      tinnitus and headache 2 days after a closed head injury. Neurological examination
      showed no additional abnormality. The EEG showed focal bifrontal slowing. CT
      revealed a fracture of the occipital bone. MRI and MRA demonstrated complete
      thrombosis of the right sigmoid and transverse sinuses. After 2 weeks of
      intravenous heparin therapy followed by warfarin, the patient's hearing improved
      and MRI and MRA showed complete recanalisation of the sigmoid and transverse
      sinuses. Venous sinus thrombosis can be an undetected sequel to head injury.
      Appropriate imaging studies should be carried out to enable therapy to be started
      as soon as possible.

PMID- 11326561
TI  - MRI of cerebral rheumatoid pachymeningitis: report of two cases with follow-up.
AB  - We report the clinical and neuroradiological features of cerebral rheumatoid
      pachymeningitis with 1 year follow-up in two patients. MRI of the head enabled
      noninvasive diagnosis of both the meningeal abnormality and its complications,
      consisting of hypertensive hydrocephalus and superior sagittal sinus thrombosis,
      respectively. Dural sinus thrombosis, very uncommon in rheumatoid arthritis, was
      confirmed by phase-contrast MRA. Worsening of the pachymeningitis at follow-up
      was observed in both patients despite regression or stability of the clinical
      picture and long-term therapy.

PMID- 11326562
TI  - Disorganised unilateral cerebellar folia: a mild form of cerebellar cortical
      dysplasia?
AB  - We describe MRI findings in two patients with disorganised foliation of one
      cerebellar hemisphere, with folia running vertically rather than horizontally.
      The thickness of individual folia and corticomedullary interdigitations were
      normal. These patients have no cerebellar neurological deficit. This rare
      abnormality is probably a maldevelopment of the hemispheric part of the posterior
      lobe of the developing cerebellum, and no clinical significance can be elicited.

PMID- 11326563
TI  - Pituitary apoplexy with optic tract oedema and haemorrhage in a patient with
      idiopathic thrombocytopenic purpura.
AB  - Bilateral optic tract oedema, left optic tract haemorrhage and subarachnoid
      haemorrhage occurred in a 70-year-old man with pituitary apoplexy associated with
      idiopathic thrombocytopenic purpura. Left optic tract haemorrhage was confirmed
      on MRI.

PMID- 11326564
TI  - Lipomatous change in a brain metastasis from malignant pleural mesothelioma.
AB  - We present a case of brain metastasis from malignant mesothelioma with lipomatous
      change.

PMID- 11326565
TI  - Cystic solitary intracerebral metastasis from prostate adenocarcinoma.
AB  - Brain metastases from prostate adenocarcinoma are rare; spread to brain as the
      only site of metastasis is even rarer. We present a patient with a large, cystic,
      solitary intracerebral metastasis from prostate adenocarcinoma. The pertinent
      literature is reviewed.

PMID- 11326566
TI  - CT appearances of chronically retained wooden intraorbital foreign bodies.
AB  - Identification of wooden intraorbital foreign bodies (WIOFB) is crucial for
      avoiding severe orbital infection. Despite careful clinical examination, WIOFB
      are often not recognised. We report the CT findings in chronically retained
      WIOFB. When not initially diagnosed, WIOFB create a granulomatous inflammatory
      foreign-body reaction. CT demonstrates the WIOFB as a linear dense structure
      surrounded by a soft-tissue mass with density similar to that of muscle,
      corresponding to the foreign-body reaction.

PMID- 11326567
TI  - Proton magnetic spectroscopic imaging of the child's brain: the response of
      tumors to treatment.
AB  - Our aim was to determine and/or predict response to treatment of brain tumors in
      children using proton magnetic resonance spectro-scopic imaging (MRSI). We
      studied 24 patients aged 10 months to 24 years, using MRI and point-resolved
      spectroscopy (PRESS; TR 2000 TE 65 ms) with volume preselection and phase
      encoding in two dimensions on a 1.5 T imager. Multiple logistic regression was
      used to establish independent predictors of active tumor growth. Biologically
      vital cell metabolites, such as N-acetyl aspartate and choline-containing
      compounds (Cho), were significantly different between tumor and control tissues
      (P < 0.001). The eight brain tumors which responded to radiation or chemotherapy,
      exhibited lower Cho (P = 0.05), higher total creatine (tCr) (P = 0.02) and lower
      lactate and lipid (L) (P = 0.04) than 16 tumors which were not treated (except by
      surgery) or did not respond to treatment. The only significant independent
      predictor of active tumor growth was tCr (P < 0.01). We suggest that tCr is
      useful in assessing response of brain tumors to treatment.

PMID- 11326568
TI  - Abnormal development of the lesser wing of the sphenoid with microphthalmos and
      microcephaly.
AB  - We report two patients with abnormal development of the lesser wing of the
      sphenoid bone, globe, optic nerve and cerebral hemisphere without stigmata of
      neurofibromatosis type 1. The lesser wing of the sphenoid bone was abnormally
      formed and was not ossified ipsilateral to the dysmorphic eye and underdeveloped
      cerebral hemisphere. Maldevelopment of the sphenoid wing may interfere with the
      normal closure of the optic vesicle and normal growth of encephalic structures,
      possibly by disturbing developmental tissue interactions. These patients may
      exhibit a type of restricted primary sphenoid dysplasia, while the sphenoid
      dysplasia of neurofibromatosis type 1 may be secondary to orbital or ocular
      neurofibromas and other factors associated with that disease.

PMID- 11326569
TI  - Haemangiopericytoma of the nasal cavity.
AB  - Haemangiopericytomas (HPC) are rare vascular tumours originating from a
      pericytes, a term coined by Zimmermann to refer to the main location of this cell
      line in the pericapillary connective tissue. HPC may arise in any part of the
      body. We report a 29-year-old man with a histologically proven nasal
      haemangiopericytoma-like tumour. The lesion was embolised through the ophthalmic
      artery before it was removed surgically. The main symptoms of nasal HPC are
      epistaxis and obstruction of the nose. Malignant and benign clinical courses have
      been described. Local recurrence and metastases may be observed years after
      initial diagnosis.

PMID- 11326570
TI  - A new patient with rhombencephalosynapsis.

PMID- 11326571
TI  - Utilization of district health services by injured persons in a rural area of
      Ghana.
AB  - INTRODUCTION: Injury is a significant health problem in many less developed
      countries. However, strategies for dealing with it have been only minimally
      addressed. GOALS: We ought to assess the pattern of health care utilization by
      injured persons in rural Ghana. We thus hoped to provide data that would assist
      in strengthening injury treatment in this setting. METHODS: Using household
      interviews, we surveyed 9442 person. We sought information on any injury during
      the previous year that resulted in one or more days of disability. Injured
      persons were interviewed regarding the mechanism of injury, treatment obtained
      and length of disability. RESULTS: During the previous year, 923 nonfatal
      injuries were reported. Half the injured persons (49%) received no formal medical
      care. When treatment was received, it was primarily delivered by a non-doctor
      staffed primary health care (PHC) clinic. Such clinics provided treatment for 30%
      of all injured persons (58% of those receiving formal medical care). Twenty
      percent of the injured received hospital-based care (39% of those receiving
      formal medical care). Among those using hospitals, the majority (92%) used
      district hospitals. CONCLUSIONS: In this setting, efforts to improve injury
      treatment should include district hospitals and PHC clinics. At both there is a
      need to advance the concept of 'essential' injury treatment services, addressing
      equipment, supplies and training.

PMID- 11326572
TI  - Application of activity-based costing (ABC) for a Peruvian NGO healthcare
      provider.
AB  - This article describes the application of activity-based costing (ABC) to
      calculate the unit costs of the services for a health care provider in Peru.
      While traditional costing allocates overhead and indirect costs in proportion to
      production volume or to direct costs, ABC assigns costs through activities within
      an organization. ABC uses personnel interviews to determine principal activities
      and the distribution of individual's time among these activities. Indirect costs
      are linked to services through time allocation and other tracing methods, and the
      result is a more accurate estimate of unit costs. The study concludes that
      applying ABC in a developing country setting is feasible, yielding results that
      are directly applicable to pricing and management. ABC determines costs for
      individual clinics, departments and services according to the activities that
      originate these costs, showing where an organization spends its money. With this
      information, it is possible to identify services that are generating extra
      revenue and those operating at a loss, and to calculate cross subsidies across
      services. ABC also highlights areas in the health care process where efficiency
      improvements are possible. Conclusions about the ultimate impact of the
      methodology are not drawn here, since the study was not repeated and changes in
      utilization patterns and the addition of new clinics affected applicability of
      the results. A potential constraint to implementing ABC is the availability and
      organization of cost information. Applying ABC efficiently requires information
      to be readily available, by cost category and department, since the greatest
      benefits of ABC come from frequent, systematic application of the methodology in
      order to monitor efficiency and provide feedback for management. The article
      concludes with a discussion of the potential applications of ABC in the health
      sector in developing countries.

PMID- 11326573
TI  - Crossing the public-private sector divide with reproductive health in Cambodia:
      out-patient services in a local NGO and the national MCH clinic.
AB  - Set within the context of recent literature on the private-public divide in the
      health sector of developing countries generally and Asia specifically, this study
      considers the major government and the major indigenous non-government clinics
      offering out-patient reproductive health services in Phnom Penh, Cambodia.
      Reproductive health is of critical importance in Cambodia, which has one of the
      highest levels of unmet need for family planning in the developing world and
      suffers from what is arguably the most severe STD and HIV/AIDS problem in Asia.
      The study is unusual in that it examines and compares aspects of service delivery
      and pricing along with the socio-economic profile and health-seeking behaviour of
      clients self-selecting services in the two settings. The socio-economic status of
      clients was much higher than the norm in Cambodia but did not differ
      significantly between the two clinics. A few service indicators suggested that
      the quality of care was better in the NGO clinic. Underlying variables--such as
      the broader mandate of the public sector institution and the significant
      discrepancy between public and private sector salaries--offer an obvious
      explanation for these differences. The Ministry of Health in Cambodia has been
      developing policies related to the NGO sector, which has expanded rapidly in
      Cambodia during the 1990s, and it is struggling to increase staff remuneration
      within the public sector.

PMID- 11326574
TI  - Evidence based primary care? A multi-tier, multiple stakeholder perspective from
      Chile.
AB  - A new challenge in health policy is the implementation of evidence-based
      practice. It is useful to look at international experiences which go beyond the
      conventional USA and UK examples. Health sector restructuring in Chile has as its
      goals: using evidence-based decision-making to reduce variations of practice,
      contain costs and increase the effectiveness of clinical practice. A key area of
      change is within primary health care. But how does the implementation of evidence
      based health care proceed in reality? In order to understand this, it was decided
      to assess the policy environment using stakeholder analysis. METHODS: Fifteen
      stakeholders from the public health sector were interviewed in depth using a
      snowball strategy for sampling. Material relating to perceptions, thoughts and
      aspirations about evidence-based innovations in primary health care was
      collected. Content analysis of the material produced a matrix of criteria and
      indicators of operational power. RESULTS: Concepts of evidence and effectiveness
      are different according to the role of each stakeholder in the health system.
      Most innovations proposed by government are related to management and
      stakeholders considered them as not being evidence-based. Informal mechanisms of
      decision-making predominated over the formal. Political issues are more important
      than formal evidence. All stakeholders felt they had power to define policy
      criteria but not to implement them. Implementation difficulties are related to
      how the system is organized and the culture within each organization. Most
      stakeholders indicated the need for human resources with appropriate knowledge
      and personal skills in order to implement these changes. These findings reveal
      again the importance of human factors within organizations. Policy-making should
      consider such processual aspects in order to implement changes in practices in
      Chilean health care system more effectively.

PMID- 11326575
TI  - The concept of effectiveness--a blind alley? A study of different interpretations
      in a Swedish county council.
AB  - Swedish health care organizations are experiencing pressure to make ever greater
      efforts to rationalize and to increase effectiveness in the way they plan and
      provide services. In order to gain a better understanding of the current practice
      of the three groups of key actors in Swedish health care--politicians, senior
      civil servants and operational managers--and their perception of effectiveness, a
      study was carried out in a Swedish county council using both qualitative and
      quantitative methods. While in general the concept of effectiveness is thought of
      as crucial, it is not clearly or uniformly defined within the organization. Each
      of the three groups defines the concept in a way that reflects their own
      function, which may lead efforts to achieve effectiveness into a blind alley.

PMID- 11326576
TI  - Coordination and integration of disability services for the elderly: a viewpoint.
AB  - The provision of disability services for the elderly in Australia is fragmented
      with areas of duplication arising chiefly from disorganized planning with the
      States and Territories providing certain services independent of Commonwealth
      contribution. It is suggested that the Commonwealth should be responsible for the
      complete provision of disability services for the elderly comprising community
      services and residential care. Private providers competing with each other for
      efficient provision of such services should be sought with financial incentives
      in funding arrangements encouraging healthy ageing thereby reducing expenditure
      in health care in the next decades.

PMID- 11326577
TI  - Using the NIOSH Pocket Guide to Chemical Hazards.

PMID- 11326578
TI  - Help for hazardous moves.

PMID- 11326579
TI  - Calming the aftershocks.

PMID- 11326580
TI  - Fighting sudden cardiac arrest: it takes a community.

PMID- 11326581
TI  - When you really are the first responder at the scene.

PMID- 11326582
TI  - ER information saves lives.

PMID- 11326583
TI  - Minding your OTCs.

PMID- 11326584
TI  - High-powered help at a DaimlerChrysler engine plant.

PMID- 11326585
TI  - Carpal tunnel syndrome. It's not just with keyboards.
AB  - CTS is often preventable. Take care of your hands when at work or at play when
      performing repetitive tasks, especially if there is also force, vibration, or
      awkward postures. Try to keep your wrists in a neutral posture, use tools and
      techniques that minimize required force, have a proper working surface height,
      design and arrange your work space to minimize the CTS risk factors, and make
      sure to have enough breaks to have sufficient recovery time. Avoid being
      overweight. If you experience pain similar to that described with CTS, see your
      medical doctor. He or she can help differentiate CTS from other upper extremity
      disorders and can help identify the most appropriate treatment approach.
      Remember, CTS is not just with keyboards.

PMID- 11326586
TI  - Functional capacity screening.

PMID- 11326587
TI  - The testing imperative.

PMID- 11326588
TI  - Drug screening & the ADA.

PMID- 11326589
TI  - Closing the gap.

PMID- 11326590
TI  - Children and adolescents in a changing media world.

PMID- 11326591
TI  - Early childhood television viewing and adolescent behavior: the recontact study.
AB  - In this Monograph, we report the follow-up of 570 adolescents who had been
      studied as preschoolers in one of two separate investigations of television use.
      The primary goal of the study was to determine the long-term relations between
      preschool television viewing and adolescent achievement, behavior, and attitudes.
      Using a telephone interview and high school transcripts, we assessed adolescent
      media use; grades in English, science, and math; leisure reading; creativity;
      aggression; participation in extracurricular activities; use of alcohol and
      cigarettes; and self-image. In each domain, we tested theories emphasizing the
      causal role of television content (e.g., social learning, information processing)
      as contrasted with those theories positing effects of television as a medium,
      irrespective of content (e.g., time displacement, pacing, interference with
      language). The results provided much stronger support for content-based
      hypotheses than for theories emphasizing television as a medium; moreover, the
      patterns differed for boys and girls. Viewing educational programs as
      preschoolers was associated with higher grades, reading more books, placing more
      value on achievement, greater creativity, and less aggression. These associations
      were more consistent for boys than for girls. By contrast, the girls who were
      more frequent preschool viewers of violent programs had lower grades than those
      who were infrequent viewers. These associations held true after taking into
      account family background, other categories of preschool viewing, and adolescent
      media use. One hypothesis accounting for the sex differences is that early
      experiences, such as television viewing, have greater effects when they
      counteract normative developmental trends and predominant sex-typed socialization
      influences than when they reinforce them. Adolescents in the study used both
      television and print media to support ongoing interests. Television content
      (e.g., entertainment, sports, or world events) predicted extracurricular
      activities, role models, and body image. The only evidence for possible effects
      of television as a medium was the positive relation of total viewing to obesity
      for girls. The medium of television is not homogeneous or monolithic, and content
      viewed is more important than raw amount. The medium is not the message: The
      message is.

PMID- 11326592
TI  - Relapses in leprosy patients treated with rifampicin plus dapsone after varying
      periods of dapsone monotherapy.
AB  - Leprosy patients treated formerly with dapsone monotherapy followed by combined
      therapy with rifampicin plus dapsone were surveyed for relapse and rifampicin
      resistance. The relapse rate was significantly low for the 482 multibacillary
      (MB) patients receiving > 12 months combined therapy compared with the 49 MB
      cases receiving < 12 months of combined therapy. The relapse rate was related to
      the duration of dapsone monotherapy prior to combined therapy. The difference in
      relapse rate in 247 paucibacillary (PB) patients following > 12 months combined
      therapy was also of significance, compared with the 66 PB cases who had received
      < 12 months combined therapy. Five strains of M. leprae isolated from relapsed
      patients were sensitive to rifampicin by mouse foot-pad test and all relapsed
      patients responded favourably to fixed duration MDT regimen for MB cases.

PMID- 11326593
TI  - Role of paucibacillary leprosy in the transmission of disease.
AB  - The objective of this study was to establish that paucibacillary leprosy also
      carried increased risk of infection to the community. All members of 100 families
      with an index paucibacillary case were clinically, bacteriologically and
      immunologically examined. The "comparison" group was sampled from suspect
      register. Fifty-six cases occurred among 944 contacts of index paucibacillary
      cases; of these, four were multibacillary and 52 were paucibacillary. In the
      "comparison" group, two contacts out of 760 developed paucibacillary leprosy.
      This difference, between the two groups, was statistically significant. All the
      56 cases in the index case families were under 20 years of age; and 50 of them
      were aged under 15 years. Male/female ratio was 2.1:1. Of the 56 cases, 28 shared
      the same bed with the index patient, 20 shared the same room and eight lived in
      the same house. Lepromin positivity rate was higher in "comparison" families
      (92.2%) than in index case families (74.6%), the difference being statistically
      significant (x = 6.09, P < 0.001). Contacts of index case families, therefore,
      were immunologically at higher risk than contacts of "comparison" families.

PMID- 11326594
TI  - Patients presenting with defined areas of sensory loss--a preliminary study.
AB  - Thirty patients presenting with circumscribed areas of clearly demonstrable
      hypoesthesia were chosen from amongst those attending this Institute. Their
      history and clinical features were recorded, lepromin test was done for reading
      at four weeks, and peripheral part of the hypoesthetic area was biopsied for
      histopathology and immunostaining. The subjects were predominantly adult males
      with the symptomatic sites limited to the extremities. On routine
      histopathological examination of the symptomatic sites, the diagnosis of leprosy,
      using defined criteria, could be made in six cases (20%). Immunostaining of the
      remaining sections showing either no pathology or a nonspecific pathology
      revealed the presence of mycobacterial antigen in five of the 24 cases (20.83%).
      Overall, leprosy could be diagnosed in 11 of the 30 cases studied (36.66%). This
      study shows that leprosy may be an important cause of circumscribed areas of
      sensory deficit.

PMID- 11326595
TI  - "Very savage rites" suicide and the leprosy sufferer in nineteenth century India.

PMID- 11326596
TI  - Splinting in leprosy.

PMID- 11326597
TI  - Pure neuritic leprosy of supraorbital nerve as unusual presentation.

PMID- 11326598
TI  - Anetoderma secondary to lepromatous leprosy.

PMID- 11326599
TI  - Crusted (Norwegian) scabies in leprosy.

PMID- 11326600
TI  - Rheumatological manifestations of leprosy and lepra reaction.

PMID- 11326601
TI  - Candidiasis in a cured MB patient.

PMID- 11326602
TI  - Polyunsaturated fatty acids levels in edible oils: a nutritional factor
      contributing to the growth of Mycobacterium leprae.

PMID- 11326603
TI  - Effects of pressure, temperature, and pH on the sonochemical destruction of 1,1,1
      trichloroethane in dilute aqueous solution.
AB  - There is an increasing interest in the application of high intensity ultrasound
      as an advanced oxidation technique. In this study, 1,1,1-trichloroethane (TCA) is
      the compound being subjected to ultrasonic irradiation. The study focuses on the
      effects of pressure (0.103-0.241 MPa), temperature (6-19.4 degrees C) and pH
      (3.96-12.5). Optimum conditions of treatment are discerned from the results of
      the experiments based on a center composite design. The results show that about
      98% of TCA can be removed in 1 h of treatment (starting concentrations average 80
      mg/l). Also, experiments indicate that the initial concentration does not affect
      destruction rate in this system. Optimum conditions as indicated by statistical
      analysis are at T = 14.2 degrees C, P = 0.212 MPa and pH = 10.9. This study also
      presents a method to normalize rate constants for changes in the power-to-volume
      ratio.

PMID- 11326604
TI  - Towards the industrial production of medicinal tincture by ultrasound assisted
      extraction.
AB  - Experiments related to the industrial production of medicinal tinctures of sage
      (Salvia officinalis L.) and valerian (Valeriana officinalis L.) were performed
      using ultrasonically assisted extraction and quality of the final tincture was
      evaluated by gas chromatography and dry residue determination. The constituents
      of the active sage compound: borneol, cineole, alpha- and beta-thujone and also
      the dry residue were measured. In the case of valerian extractions, the
      efficiency of sonicated extraction was compared with classical extraction. The
      course of only the dry residue was monitored. The influence of ultrasound on the
      quality of valerian tincture was examined by HPLC.

PMID- 11326605
TI  - The sonochemical arylation of malonic esters mediated by manganese triacetate.
AB  - The intermolecular arylation of malonate esters in acetic acid solution in the
      presence of manganese(III) triacetate is known to proceed via an Electron
      Transfer mechanism. Under sonication, this reaction undergoes only minor changes.
      In contrast, the intramolecular reaction of dimethyl alpha-(3
      phenylpropyl)malonate provides a new case of sonochemical switching, with the
      formation of compounds 7-9, while conventional thermal conditions generate only
      the bicyclic compound 6. Reactions using the more powerful oxidant, cerium
      ammonium nitrate are governed by the formation of the nitrate ester 11. Compounds
      7-9 are isolated in yields lower than with MnTA, and in proportions depending on
      the conditions, thermal or sonochemical.

PMID- 11326607
TI  - Dissolution of salts crystallised in building materials using ultrasound: an
      alternative to NORMAL (1983) standard methodology.
AB  - Our aim in the present work is to extract salts from ornamental stone using a
      faster and less tedious method than the customarily used NORMAL method [NORMAL,
      Dosaggio dei Sali Solubili, CNR-ICR, Roma, Italy (1983) 13/83]. For extraction in
      aqueous medium, the latter method requires shaking for 72 h at a temperature of
      60 degrees C. Our aim is to attempt to shorten this time to less than 1 h using
      ultrasound. The results of the present study indicate that there is a good
      correlation between the amount of salts extracted applying the method described
      in the NORMAL (1983) normative and the amounts extracted with the method proposed
      here, subjecting the material to ultrasound (50 KHz) for 45 min.

PMID- 11326606
TI  - Efficient synthesis of (+/-)-7-isopropyl-2,10-dimethyl-8(E),10-undecadien-4-one
      and 3,7-dimethyl-11-oxo-2(E),6(E)-dodecadienol (oxocrinol) under ultrasound.
AB  - A simple and convergent synthesis of the title compounds has been achieved
      involving Zn-Cu couple catalysed conjugate addition of allylic halides to
      alpha,beta-unsaturated carbonyl compounds promoted by ultrasonic waves in aqueous
      medium as a key step in good overall yields.

PMID- 11326608
TI  - New ultrasonically prepared Co-based catalysts for Fischer-Tropsch synthesis.
AB  - An extensive study of different preparation methods for Co/SiO2 catalysts is
      reported in this paper. In addition to the conventional impregnation, other more
      innovative methods are used including ultrasound. The prepared samples are fully
      characterized and tested in the CO hydrogenation (Fischer-Tropsch synthesis). The
      best catalytic performance, both as CO conversion and hydrocarbons selectivity,
      is shown by one of the sample prepared using ultrasound.

PMID- 11326609
TI  - Investigation of the effects of ultrasound on vegetal tissues during solvent
      extraction.
AB  - The paper presents an insight into the mechanism of the ultrasonic enhancement of
      solvent extraction through the effect of ultrasound on the vegetal material
      involved. Thus, a series of experiments has been developed to investigate the
      effect of ultrasonic energy on the vegetal material and the solvent used. Several
      results concerning the ultrasonic extractive value, ultrasonic swelling index and
      the effects of frequency on vegetal material are presented.

PMID- 11326610
TI  - Ultrasonic degradation of trichloroethylene and chlorobenzene at micromolar
      concentrations: kinetics and modelling.
AB  - Although most papers in the field of sonochemical degradation of volatile
      organics in aqueous media describe experiments at the millimolar concentration
      range, this study focuses on the degradation kinetics of chlorobenzene (CB) and
      trichloroethylene (TCE) in the micromolar range. It was found that the reaction
      kinetics increase with decreasing initial substrate concentrations. For example,
      the pseudo-first-order reaction rate constant of CB increases by a factor of
      14.3, if the initial concentration drops from 3440 to 1 microM. Previous work in
      the millimolar range has shown that the degradation of these volatiles is mainly
      due to pyrolytic reactions. The enhancement of the reaction kinetics at lower
      concentrations, in this work, could no longer be explained by this mechanism,
      even by taking into account the effect of the concentration of the solutes on the
      reaction temperature. Therefore, a new model was developed, incorporating gas
      phase OH radical induced degradation, next to pyrolysis. The model, fitting the
      experimental results, illustrated that at micromolar concentrations the OH
      radical induced degradation becomes significant. Simulations showed that at
      initial concentrations of CB > 1000 microM degradation is due to pyrolysis for
      over 99.97%, but it was also demonstrated that at concentrations between 1 and 5
      microM, the OH radical mechanism contributed 48.5% of the total degradation.

PMID- 11326611
TI  - Evidence for the emission of 'alkali-metal-noble-gas' van der Waals molecules
      from cavitation bubbles.
AB  - Visible emission spectra in the vicinity of resonance lines of alkali metals were
      recorded from acoustically cavitating aqueous and 1-octanol solutions (acoustic
      frequency: 20 kHz; solutes: Ar (or Kr), NaCl, RbCl or rubidium 1-octanolate). The
      maximum intrabubble density deduced from line shift data was approximately 5 +/-
      0.7 x 10(26) m-3, i.e. approximately 18 +/- 2 amagats. It is demonstrated that
      (i) the emission from alkali metals arose from the gas phase of bubbles, (ii) the
      blue satellite and line distortions were induced, respectively, by B2 sigma+ - X2
      sigma+ and A2II - X2 sigma+ transitions of 'alkali-metal/rare-gas' van der Waals
      molecules and (iii) excitation/de-excitation mechanisms are chemiluminescent in
      essence.

PMID- 11326612
TI  - Ultrasonic effects on electroorganic processes--Part 20. Photocatalytic oxidation
      of aliphatic alcohols in aqueous suspension of TiO2 powder.
AB  - Ultrasonic effects in a suspension system were examined using the photocatalytic
      oxidation of 2-propanol to acetone and of ethanol to acetaldehyde in the aqueous
      suspension of TiO2 powder as a model reaction. The formation rate of acetone was
      significantly increased under ultrasonic irradiation. The oxidation reaction
      under ultrasonic irradiation was affected in a different manner from that in
      silence by reaction conditions such as ultrasonic power, stirring speed, amount
      of TiO2, concentration of 2-propanol, and pretreatment of the TiO2 powder.
      Furthermore, it was also observed that the particle size of the TiO2
      photocatalyst powder was increased due to the particle agglomeration by
      ultrasonic irradiation, and consequently it was suggested that ultrasound
      activates the surface of the catalyst. These results are discussed on the basis
      of not only the activation of the photocatalyst but also ultrasonic enhancement
      of mass transport of 2-propanol molecules.

PMID- 11326613
TI  - Effect of ultrasonic frequency on polymerization of styrene under sonication.
AB  - The effect of ultrasonic frequency on polymerization of styrene under sonication
      at 50 degrees C was studied at the frequencies of 23.4, 45.7, 92, 518 kHz and 1
      MHz. Polymerization under sonication was carried out at the ultrasonic intensity
      that gives the same reaction rate of decomposition of porphyrin. The magnitude of
      the polymerization rate increases in the order of 92, 45.7 and 23.4 kHz. At the
      high frequencies of 518 kHz and 1 MHz, no polymerization was observed. These
      facts mean that there is an optimum frequency in the range from 92 to 518 kHz for
      effective polymerization. The average-number molecular weights at the sonication
      time of 3 h are 5.5 x 10(4), 8.0 x 10(4) and 11.5 x 10(4) for the irradiated
      frequencies of 92, 45.7 and 23.4 kHz, respectively. Sonication for 3 h at 92 kHz
      gives polystyrene with very high polydispersity, about 5.0, in comparison with
      the results obtained at 23.4 and 45.7 kHz. These observations indicate that
      polymerization under sonication is influenced by the irradiated frequency.

PMID- 11326614
TI  - Effect of sonication on nitroxide-controlled free radical polymerization of
      styrene.
AB  - Effect of sonication on the autopolymerization of styrene in the presence of
      2,2,6,6-tetramethylpiperidinyl-1-oxy as the mediating radical was investigated at
      110-135 degrees C. The thermal polymerization under sonication proceeded in the
      manner of a "living" radical polymerization to afford well-defined polystyrene.
      The sonication was found to decrease the induction period and increase the
      polymerization rate.

PMID- 11326615
TI  - Sonochemical synthesis of hydroxyapatite from H3PO4 solution with Ca(OH)2.
AB  - Ultrasound was irradiated to an aqueous suspension containing phosphoric acid
      (H3PO4) and calcium hydroxide (Ca(OH)2) to investigate the sonochemical effect on
      preparation of hydroxyapatite (Ca10(PO4)6(OH)2, HAp). HAp monophase could be
      synthesized from the suspension sonicated for 60 min. The reaction for HAp was
      promoted more effectively than that of the heating method conducted at the same
      conditions as those for the sonicating method. The equilibrium pH of the
      suspensions sonicated over 60 min was maintained neutral, suggesting that the
      synthesis reaction was almost completed. The ultrasonic irradiation played an
      important role to progress the heterogeneous reaction and the preparation of very
      fine HAp powder.

PMID- 11326616
TI  - Curing properties of furfuryl alcohol condensate with carbonaceous fine particles
      under ultrasonication.
AB  - Ultrasonic treatment (sonication) was carried out through the curing process of
      furan resin by using an ultrasonic homogenizer at the frequency of 20 kHz and the
      various intensities (0-90 W). Various carbonaceous fine particles were added to
      furan resin to investigate the change of polymerization degree. The curing rate
      of furan resin was accelerated by sonication, which increased the polymerization
      degree with an increase in ultrasound intensity. The increase of curing rate was
      also observed by small additions of carbonaceous fine particles. In this case,
      the curing rate was increased with an increase in the specific surface area on
      additives.

PMID- 11326617
TI  - Synthesis of ethyl alkylidene alpha cyanoacetates under ultrasound irradiation.
AB  - Condensation of ketones with ethyl cyanoacetate catalysed by ammonium acetate
      acetic acid results in ethyl alkylidene alpha cyanoacetate in 31-89% yield under
      ultrasound irradiation.

PMID- 11326618
TI  - Sonochemical synthesis of iron phosphide.
AB  - The sonochemical reaction of Fe(CO)5 and triethylphosphine has been found to
      produce solid amorphous iron phosphide of composition FeP. The resulting compound
      was characterized by elemental microanalysis, scanning electron microscopy,
      energy-dispersive X-ray analysis, and Debye-Scherrer powder X-ray diffraction. X
      ray powder patterns were obtained after the amorphous material had been heated
      above 950 degrees C and then slowly cooled to induce crystallization. This
      reaction provides the first use of ultrasound to sonochemically synthesize
      amorphous phosphide semiconductor materials from organometallic precursors.

PMID- 11326619
TI  - Practical issues and concepts in vagus nerve stimulation: a nursing review.
AB  - Estimates of epilepsy incidence among the U.S. population range between 0.5% and
      1%. The most common type of seizure in adult patients is partial onset.
      Approximately 20% of these patients are refractory to antiepileptic drug therapy
      and experience intolerable side effects such as confusion, dizziness, weight
      gain, lethargy, and ataxia. The ketogenic diet appears to be beneficial for
      children but is not considered a standard option for adults. Epilepsy surgery can
      be an option for many and may offer control or a reduction in seizures. However,
      many patients are opposed to cranial surgery or may not tolerate the ketogenic
      diet. Recent advances in biomedical technology and perfection in surgical
      techniques have shown vagus nerve stimulation (VNS) using the Neuro Cybernetic
      Prosthesis (NCP) system is an effective new treatment option in reducing seizure
      frequency. On July 16, 1997, the U.S. Food and Drug Administration (FDA) approved
      the use of the NCP for vagus nerve stimulation, as an adjunctive treatment for
      refractory partial onset seizures in adults and adolescents over 12 years of age.
      Murphy et al. and Wheless have reported similar results in children younger than
      12 years. VNS represents the first therapy using a medical device approved by the
      FDA for the treatment of refractory seizures. An estimated 10,000 patients have
      been implanted with the device.

PMID- 11326620
TI  - Career opportunities in neuroscience nursing.
AB  - The responses from Europe, Asia, Australia, and America illustrate the diversity
      in the development of the nursing profession and in the possibilities of career
      advancement for nurses in different countries. Whereas advanced nursing practice
      is a natural component of the healthcare system in North America, and gradually
      becoming so in Australia and the United Kingdom, it is far from reality in many
      other countries. Although the presence or absence of such opportunities
      necessarily does not reflect the quality of nursing or skills of practicing
      nurses, their absence clearly prevents professional development, acceptance, and
      recognition for nurses as a group. In several countries, training programs and
      courses are available from individual hospitals and other sources. However, as
      long as such programs and, in particular, the qualifications they lead up to, are
      not recognized by health authorities at an official level, their contribution
      beyond that of improving personal knowledge of the trainee is very limited.
      Undertaking such training may be beneficial for nurses in their present positions
      but is of little use if they want to change to a new job. Unless the new employer
      chooses to acknowledge such qualifications, he does not have to. A nurse is a
      nurse, is a nurse. Needless to say, this also has important implications for
      nurses' salaries. This was illustrated in a recent survey that identified the
      average annual salary for nurses in the United States as $37,980 (U.S.). In
      comparison, official statistics from the Swedish Association of Health
      Professionals state that the average annual nurse salary in Sweden in 1999
      approximated $25,146 (U.S.), with mean salaries ranging from $23,871 (U.S.)
      (hospital ward nurses) to $33,724 (U.S.) (nurse managers and executives).
      Although I have not been able to find old comparative data from other countries,
      informal sources have indicated that the pattern is similar. The need for
      increased and improved career opportunities for nurses is apparent. How these
      should be designed and the exact roles of different categories of nurses in
      various countries will have to be dictated by local needs and other
      circumstances. However, the scheduled inclusion of this topic at the forthcoming
      WFNN Congress in Sydney will provide an excellent opportunity for nurses from
      across the globe to discuss these issues and perhaps initiate work towards
      setting common international goals for neuroscience nurses. In parallel, it is of
      outstanding importance that contributions by advanced practice nurses are
      evaluated in a broad and scientifically sound manner in countries in which they
      are established and being introduced. Further comments on the topic are highly
      appreciated!

PMID- 11326621
TI  - Successful incorporation of the Severe Head Injury Guidelines into a phased
      outcome clinical pathway.
AB  - Clinical pathways have been proven to be valuable tools in improving outcomes in
      patients with neurological diagnoses. However, their use with trauma populations
      has been limited. The unpredictable nature of trauma makes it difficult to
      develop a day-by-day plan of care that would be applicable to all patients with
      the same trauma diagnosis. Nevertheless, a severe traumatic brain injury (TBI)
      clinical pathway was developed and implemented at a Level 1 Trauma Center with
      significant reductions in length of stay and number of ventilator days. With the
      publication of the Guidelines for the Management of Severe Head Injury, this
      pathway was refashioned into a severe TBI phased-outcome pathway. Rather than a
      day-by-day plan of care, this clinical pathway consists of four phases of care:
      (a) admission to the intensive care unit, (b) acute critical care, (c) mobility
      and weaning, and (d) pre-rehabilitation. After 12 months, the improvements
      accomplished by the original pathway have been maintained or exceeded.

PMID- 11326622
TI  - Neurosurgery for movement disorders.
AB  - Movement disorders have been treated neurosurgically since the 1930s. Current
      diagnoses for neurosurgical interventions are Parkinson's disease, essential
      tremor, multiple sclerosis, and some dystonic disorders such as idiopathic
      torsions dystonia. By using stereotactic image-guided techniques, targets can be
      chosen to treat different symptoms: the ventrointermediate nucleus of thalamus
      for tremor; the internal globus pallidus for dyskinesia, dystonia, rigidity,
      akinesia, and tremor; and the subthalamic nucleus for all cardinal symptoms in
      advanced Parkinson's disease, including drug-induced hyperkinesia (secondary to
      reduced drugs). The surgical approaches can be divided into three main groups:
      destructive (e.g., lesional surgery), reversible and adjustable (e.g., permanent
      electro-inhibition/stimulation), and reconstructive (e.g., fetal nerve cell
      transplantation). Reconstructive procedures, which are not discussed here, are
      still in the early developmental phase. All the methods have advantages and
      disadvantages; therefore, it is important that the right target and technique be
      chosen for each patient.

PMID- 11326623
TI  - The multiple sclerosis nurse as patient educator.
AB  - Patient education is an important part of neuroscience nursing. New treatments,
      such as beta interferon self-injections, have challenged nurses. The purpose of
      this study was to analyze the patient education given by 35 Finnish nurses who
      work with patients who have multiple sclerosis. The content and didactic
      solutions of patient education, evaluation of patients' learning skills, and
      learning outcomes were analyzed. Also, successful and unsuccessful patient
      education experiences are described. The results showed that patient teaching is
      based on individual and unstructured approaches. The role of the patient is
      important, and there is need for more systematic evaluation of learning outcomes.
      Results from teaching of beta interferon self-injections are similar. In general,
      more systematic research in this area is required.

PMID- 11326624
TI  - Chiari I malformation: clinical presentation and management.
AB  - Chiari malformations are cerebellar anomalies. The four types of Chiari
      malformations, as described more than 100 years ago by Dr. Hans Chiari, have
      neither anatomic nor embryologic correlation. Their only commonality is that they
      all involve the cerebellum. Chiari I malformation consists of herniation of the
      cerebellar tonsils into the foramen magnum, thus crowding the craniocervical
      junction. Chiari II malformation is almost exclusively associated with
      myelomeningocele and hydrocephalus. It consists of herniation of not only the
      tonsils but also all the contents of the posterior fossa into the foramen magnum.
      This herniation involves the brainstem, fourth ventricle, and cerebellar vermis.
      Chiari III and IV malformations are rare. Chiari III represents an encephalocele
      (external sac containing brainstem and posterior fossa contents); thus, the
      cerebellum and brainstem are descending not only into the spine, but also into an
      external sac. Chiari IV consists of cerebellar hypoplasia. The Chiari I
      malformation has the latest mean age of clinical presentation. A Chiari type I
      anomaly presenting in adulthood is the focus of this article. Surgery is
      indicated with neurological dysfunction, symptomatic syrinx, or hydrocephalus. Of
      all Chiari I patients, 15%-20% will have hydrocephalus. For some of them, the
      hydrocephalus will resolve with ventriculoperitoneal shunting, alleviating the
      need for a Chiari decompression. Long-term prognosis for patients with
      symptomatic Chiari type I malformations who undergo surgical treatment is
      variable, based on the patients' presenting symptoms and spinal cord cyst
      response.

PMID- 11326625
TI  - Neurology patient education materials: do our educational aids fit our patients'
      needs?
AB  - The purpose of this study was to assess the suitability of various neurology
      patient education brochures, as well as neurology information on the World Wide
      Web, to determine whether they were appropriate for patients with low literacy. A
      convenience sample of 520 patients in university-based public and private
      neurology clinics participated. In this cross-sectional study, the patients'
      reading levels were assessed by using the Rapid Estimate of Adult Literacy in
      Medicine. Forty-three patient education materials were assessed for reading level
      by using the Fog Index and for suitability characteristics (including content,
      type and relevance of graphics, layout, type size and fonts, and motivating
      qualities) by using the Suitability Assessment of Materials. The mean education
      level of patients was 12th grade; however, the mean reading level was 7th-8th
      grade. Of the assessed materials, 91% were written at a 9th-grade level or above,
      even though only 58% of patients read at a 9th-grade level. Only 14% of the
      materials were considered to have superior suitability, whereas 58% were
      adequate, and 28% were determined not suitable. Thus, the available neurology
      patient education aids are not matched to the patient population or to the
      average U.S. reading levels. Ideally, information needs to be written at a 9th
      grade level or below. Instructional graphics, simpler words, patient interaction,
      and cultural sensitivity improve material suitability.

PMID- 11326626
TI  - Giving credit where credit is due--authorship versus acknowledgment.

PMID- 11326627
TI  - Opposed to the use of antibiotics in pulse therapy.

PMID- 11326628
TI  - Opposed to the use of antibiotics in pulse therapy--comment.

PMID- 11326629
TI  - An ethicist's commentary on veterinary involvement with laws banning pitbulls and
      pitbull crosses.

PMID- 11326630
TI  - Prevalence of sucking and chewing lice on cattle entering feedlots in southern
      Alberta.
AB  - Beef calves from 2 sources entering southern Alberta feedlots in the winters of
      1997-98 and 1998-99, were surveyed for the presence of lice. A random sample of
      multiple source (MS), that is, auction market-derived, calves entering commercial
      feedlots and single source (SS) calves entering a backgrounding feedlot were
      examined for the presence of lice at entry to the feedlot. A standardized
      examination, which involved hair-part examination of 8 louse predilection sites,
      was conducted on each selected calf to determine prevalence and intensity of
      infestation. The long-nosed sucking louse, Linognathus vituli, was the most
      commonly encountered species. This species infested from 57.8% to 95.6% of the
      calves selected from both MS and SS calves during both winters. Louse index
      values, indicating intensity of infestation, for L. vituli ranged from 1 to 243
      lice per animal. The chewing louse, Bovicola bovis, was present on MS and SS
      calves only in the winter of 1998-99. The louse index values for B. bovis ranged
      from 1 to 230 lice per animal. Mixed infestations of the L. vituli and B. bovis
      were common. The little blue cattle louse, Solenopotes capillatus, was present
      only on the SS calves in the winter of 1997-98. The short-nosed sucking louse,
      Haematopinus eurysternus, was present at very low intensities, 1-2 lice per
      animal, on 2.6% to 4.4% of the MS calves during both winters. Comparison of
      results from the current study with published literature suggests that efforts to
      determine the economic impact of louse infestations are confounded by the lack of
      a uniform method to assess louse population levels.

PMID- 11326631
TI  - A combined frontal and maxillary sinus approach for repulsion of the third
      maxillary molar in a horse.
AB  - The 3rd maxillary molar is a difficult tooth to remove by extraction or
      repulsion. A combined frontal and maxillary approach provides good exposure for
      repulsion of this tooth, debridement of the sinuses, and placement of an alveolar
      seal. The improved exposure should minimize operative difficulties and
      postoperative complications.

PMID- 11326632
TI  - Verminous arteritis in a 3-month-old thoroughbred foal.
AB  - Strongylus vulgaris migration and cranial mesenteric arterial thrombus formation
      resulted in fatal colic in a 3-month-old Thoroughbred foal. Vascular damage
      associated with S. vulgaris occurs early in the course of infection and, despite
      widespread use of broad-spectrum anthelmintics, appropriate management is still
      essential to minimize exposure of young animals to this parasite.

PMID- 11326633
TI  - Recurrent diarrhea associated with enterotoxigenic Clostridium perfringens in 2
      dogs.
AB  - Two dogs were diagnosed with enterotoxigenic Clostridium perfringens-associated
      diarrhea. Diarrhea was responsive to antimicrobial therapy, but recurred after
      treatment was ceased. Clostridium perfringens enterotoxin was present in feces
      during diarrheic episodes but not when feces were normal. Both dogs responded to
      a prolonged course of oral cephalexin and dietary modification.

PMID- 11326634
TI  - Prevalence of gastrointestinal helminths in domestic bison herds in northwestern
      Alberta.
AB  - A fecal survey was conducted to determine the prevalence of gastrointestinal
      helminth eggs found in 431 domestic bison from 22 herds. Eggs detected (percent
      of herds affected in parentheses) were: strongyle-type (100%), Capillaria sp.
      (63.6%), Moniezia sp. (54.6%), Nematodirus sp. (50%), Trichuris sp. (40.9%), and
      Strongyloides sp. (9.1%).

PMID- 11326635
TI  - The microbiological effects of trimming sticking wounds in pasteurized pig
      carcasses.
AB  - Neither pasteurizing of uneviscerated carcasses nor trimming reduced the numbers
      of total aerobic bacteria recovered from sticking wounds in pig carcasses.
      However, trimming after pasteurizing increased the numbers of coliforms and
      Escherichia coli recovered from sticking wounds, whereas pasteurizing without
      trimming reduced these counts.

PMID- 11326636
TI  - Subcutaneous fibrosarcoma in an aged guinea pig.
AB  - A 9-year-old, female guinea pig was diagnosed with a subcutaneous fibrosarcoma
      overlying the ventral thorax. The mass was invasive within the subcutis without
      extension into surrounding structures or organ systems. Other findings included
      cystic ovaries, renal cortical cysts, nodular hyperplasia of the liver, and
      myocardial fibrosis with pulmonary hypertension.

PMID- 11326637
TI  - Diagnostic guided surgical therapy of gastrointestinal cancer.
AB  - Stage adapted treatment of gastrointestinal cancer including extended
      preoperative work-up, multimodal therapeutic options as well as complete tumor
      resection becomes more important in the last years. Besides conventional tumor
      staging, the performance of endosonography or surgical laparoscopy seems to be
      mandatory in planning limited surgical or endoscopic procedures with curative
      intent as well as preoperative therapy in locally advanced tumors or locoregional
      recurrences and metastases. Therefore, in modern surgical oncology, diagnostic
      guided treatment of the individual tumor situation represents the optimal therapy
      nowadays.

PMID- 11326638
TI  - A prognostic value of syndecan-1 in gastric cancer.
AB  - BACKGROUND: Syndecan-1, a cell surface heparan sulphate proteoglycan, has a role
      in cell adhesion, maturation and proliferation. Syndecan-1 has been reported to
      be a promising prognostic marker in various cancer forms. MATERIALS AND METHODS:
      We analysed tumour specimens from 296 gastric cancer patients. Syndecan-1
      expression was studied by immunohistochemistry. RESULTS: Syndecan-1
      immunoreactivity was observed in 234 (79%) patients. The expression of syndecan-1
      did not correlate significantly with the presence of lymph node metastases,
      distant metastases, peritoneal spreading, penetration depth, tumour size, tumour
      location, Borrmann's classification, Lauren's classification, age or gender.
      Syndecan-1 immunoreactivity correlated significantly with survival in the whole
      patient series (p = 0.0499) and also in the subgroup of patients with stage I
      cancer (p = 0.0417), but not in patients with stage II, III or IV disease. In
      multivariate survival analysis, stage of disease and tumour size emerged as the
      only independent prognostic factors. CONCLUSIONS: In conclusion,
      immunohistochemical expression of syndecan-1 is a potential prognostic factor in
      gastric cancer, especially in patients with stage I disease.

PMID- 11326639
TI  - Epstein-Barr virus DNA, intermediate filaments and epithelial membrane antigen in
      nasopharyngeal carcinoma.
AB  - The aim of this study was to investigate the expression of intermediate filaments
      (cytokeratin, vimentin), epithelial membrane antigen (EMA) and the presence of
      Epstein-Barr virus (EBV) DNA in undifferentiated nasopharyngeal carcinoma (NPC).
      A high incidence of nuclear signals in NPC was found in primaries and regional
      lymph node metastases (70%), using 35S-labelled probes of EBV plasmids for in
      situ hybridization. Keratinizing squamous cell carcinomas were EBV-negative. All
      carcinomas were immuno-reactive for cytokeratin (KL-1). 45% of the carcinomas
      were positive for vimentin. The expression of epithelial membrane antigen was
      restricted to epithelial cells and reduced in NPC as compared to the distribution
      pattern of cytokeratin. Both EBV DNA and vimentin in NPC were present in 9 cases.
      However, in 5 cases NPC were harboring EBV but were not immunoreactive for anti
      vimentin antibodies. In no case was a vimentin-positive NPC also EBV-negative.
      The identification of cytokeratin subtypes revealed no specific cytokeratin
      pattern in NPC. The expression of vimentin in NPC is not specific for EBV, but
      seems to reflect the loss of inter-epithelial contact in anaplastic carcinomas.

PMID- 11326640
TI  - Dose-response relationships on the expression profile of cytokeratins and
      vimentin in rat submandibular glands following fractionated irradiation.
AB  - OBJECTIVE: The extent of radiogenic damage in salivary gland (SG) tissue depends
      on the radiation dose (RD), the fractionation (FN) and the localization of SG in
      the radiation field (RF). While the functional restriction and the radiogenic SG
      tissue damage are well documented using histomorphological, electron-microscopic
      and enzyme-histochemical methods, immunohistochemical analysis (IH) of
      cytokeratins (CK), epithelial differentiation markers, and vimentin, a marker of
      mesenchymal cells, are rare. Previous studies have shown stronger
      immunoreactivities of CK in irradiated glands exposed to 60 Gy total dosage. This
      study was performed to examine dose dependence and alterations related to age,
      RF, and latency of irradiation. METHODS: In 124 rat mandibular SG we investigated
      the vimentin and CK staining profile dependent on age [1 year (y) vs. 1 1/2 y],
      on FN [2 Gy/day up to a total dosage of 20/40/60 Gy (x-rays)], on RF (inside vs.
      outside RF) and on the time since irradiation (1/2 y vs. 1 y) using IH. RESULTS:
      The mouse monoclonal anti-CK antibodies [(AB) D5/16B4, Ks 13.1, E 3, K8.12, Ks
      18.04, against CK 5-6, CK 13, CK 17, CK 13-15-16, CK 18) and the polyclonal anti
      vimentin AB GP53 identified different epithelia and mesenchymal structures in rat
      SG tissue, including excretory duct cells (ECD), striated duct cells (SD),
      granular convoluted tubules (GTC), intercalated duct cells (ICD) and
      myoepithelial cells (MC). MC and mesenchymal cells were positive for vimentin AB.
      The different CK were detected in cell type-specific patterns and at variable
      levels in non-irradiated SG. In irradiated SG most cell types showed
      significantly stronger staining for various CKs. With increasing RD from 20 Gy to
      60 Gy we found an increasing staining reaction. The CK staining profile up to 20
      Gy was non-uniform and did not differ significantly from controls. Age and time
      since irradiation played a minor role or had no significant effect on staining.
      CONCLUSIONS: The CK and vimentin immunoreactivity showed dose-dependent
      increasing expressions, which could contribute to radiogenic cell and tissue
      damage. In some tissue structures a possible scattered irradiation effect should
      be mentioned. Age and time since irradiation (chosen in the study) had a minor or
      insignificant effect on staining profiles.

PMID- 11326641
TI  - P53-mutation in smears of oral squamous cell carcinoma.
AB  - The tumor suppressor gene p53 encodes for an important cell cycle regulatory
      protein. Loss of the protein's function is probably important for the development
      of a variety of malignant diseases, including oral cancer. Up to present
      knowledge, the mutations of the p53 gene are one of the most frequent genetic
      alterations detectable in human cancer. The aim of this study was to explore the
      capability of molecular diagnostics to identify p53 mutations (exon 5-8) in
      smears of the oral mucosa (polymerase chain reaction, temperature gradient gel
      electrophoresis). Thirty two patients with oral squamous cell carcinoma comprised
      the study. Biopsies of the tumor, smears of the ulcer, and smears of apparently
      healthy mucosa were collected from these cancer patients. Smears of 35 healthy
      volunteers served as controls. P53-mutations were detected in 14 of the 32 cancer
      patients (44%). The same mutations was also detected in the biopsy in all cases.
      In addition, swabs of apparently normal mucosa harboured p53-mutated cells in 4
      of these 14 patients. No mutation was found in healthy volunteers. Our
      investigation showed the suitability of swabs for gaining sufficient material to
      detect p53 gene mutations in oral squamous cell carcinoma.

PMID- 11326642
TI  - Expression of cytokeratins and additional markers in undifferentiated lymph node
      metastases of the neck.
AB  - OBJECTIVE: A variety of carcinomas (CA) can metastasize to the lymph nodes of the
      neck. Differentiation of CA in the lymph nodes according to their resemblance to
      the structure of origin is the basis of histopathological diagnosis. However,
      during the course of the disease, e.g. tumor recurrence after ablative surgery,
      these tissues can completely lose the ability to imitate typical structures of
      the organ that gave rise to malignant transformation. This can result in the
      inability of the pathologist to identify the origin of the metastases. The
      identification of the large group of cytokeratins (CK) as a member of the family
      of intermediate filaments has improved the diagnosis of epithelial tissues. An
      attempt was made to use CK antibodies to identify the organ of origin of poorly
      differentiated and anaplastic lymph node metastases of the neck. METHODS: We
      investigated 34 routinely fixed (formalin/paraffin) lymph node metastases of the
      neck or specimens of these metastases. The tumors differed in terms of suspected
      primary tumor site and differentiation. Depending on the case history, diagnosis
      was performed by hematoxylin-eosin staining and by immunohistochemical staining
      of sections using antibodies against CK (CK nos. 1-10-11, 5-6, 6-8, 7, 8, 8-18,
      13-15-16, 19 and 20) and against additional markers [vimentin, leukocyte common
      antigen (LCA), S-100, gross cystic disease fluid protein (GCDFP) and Epstein-Barr
      virus-induced latent membrane antigen (EBV-LMP)]. RESULTS: The histopathological
      diagnosis was lympho-epithelial CA (8 cases), thyroid gland CA (2 cases), mammary
      gland CA (5 cases), bronchial CA (4 cases), basaloid CA (3 cases), clear cell CA
      (2 cases), sebaceous CA (1 case) and pharyngeal CA (9 cases). Some metastases
      were anaplastic in differentiation (G3-4). The marker expression in the
      immunohistological sections supported the histopathological findings. In some
      cases diagnosis succeeded especially in evaluating the marker expression. For
      example, in lympho-epithelial CA the epithelial tumor cell formations were
      positive for CK 5-6 antibodies, while expression in the lymphatic cells was
      lacking. In mammary gland CA the tumor cells were clearly identified by their
      positivity for CK 7 and GCDFP antibodies, in contrast to the negative
      infiltrating cells surrounding the tumor cells. CONCLUSIONS: In light of the case
      history details and the histopathological findings, immunohistological expression
      of various markers, especially the identification of CK subtypes, supported the
      differential diagnosis. In some cases the diagnosis may be established only by
      using CK profile and additional markers.

PMID- 11326643
TI  - Gallbladder bile tumor marker quantification for detection of pancreato-biliary
      malignancies.
AB  - BACKGROUND: The pre-operative differentiation of tumors of the pancreas, Papilla
      of Vater and the biliary tract is still unsatisfactory. Tumor marker analysis of
      the pancreatic juice did not improve the pre-operative diagnosis by a great deal.
      METHODS: Bile from resected gallbladders of patients suffering from carcinomas of
      the pancreato-biliary system was analysed for CA 19-9, CEA, CA 72-4, CA 125 and
      AFP concentrations. The results were compared to patients suffering from acute
      cholecystitis, cholecystolithiasis as well as those suffering from benign tumors
      of the pancreato-biliary region. RESULTS: Extreme high CA 19-9 concentrations
      were found in bile. Evaluations of the tumor-antigens CA 19-9, CA 72-4 and CEA in
      gallbladder bile were superior to any serum and pancreatic juice examination with
      respect to sensitivity and specificity. Observed sensitivities amounted to 100%
      for patients suffering from bile duct carcinoma (CA 19-9) and papillary carcinoma
      (CEA) at a specificity of 100%. CA 19-9 showed a sensitivity of 76.5% for
      pancreatic carcinomas at a specificity of 96.4%. CA 19-9 showed significant
      differences for the local tumor burden and for the degree of lymph node
      metastasis. Examination of tumor antigens in the gallbladder results in a high
      degree of discrimination for malignant and benign lesions of the subhepatic
      pancreato-biliary system. CONCLUSIONS: CA 19-9 must follow a entero-hepatic
      circulation, since it showed raised bile concentrations (factor: 10(4)) compared
      to serum analysis. Analysis of CA 19-9, CEA and CA 72-4 gives an opportunity for
      improvement in the detection of cancers of the pancreato-biliary system. Since
      the clinical important differentiation of tumors of the head of the pancreas
      (carcinoma vs. pancreatitis) remains unclear, an improvement by bile analyses
      must be assumed.

PMID- 11326645
TI  - Carcinoembryonic antigen for the detection of recurrent disease following
      curative resection of colorectal cancer.
AB  - BACKGROUND: During recent years a discussion about cost-effectiveness and
      importance of follow-up determination of carcinoembryonic antigen (CEA) after
      curative resection of large bowel cancer has developed. PATIENTS AND METHODS:
      Between 1990 and 1998 follow-up CEA levels of 1,321 patients after curative
      colorectal cancer resection were prospectively collected in cooperation with
      family physicians, CEA determinations were made with different assays by various
      laboratories. The reported findings were adjusted for the different methods used.
      RESULTS: 306 patients developed recurrent disease following curative cancer
      resection (23.2% of all patients). Regarding the role of follow-up CEA
      determination, they were divided into: I. no preoperative CEA
      determination/insufficient follow-up (N = 47); II. no elevation of CEA with
      primary cancer, a) elevation with recurrent disease (N = 62), b) no elevation at
      any time point (N = 53), c) role of CEA not completely elucidated (N = 41); III.
      elevated CEA levels with primary cancer, a) no increase with recurrent disease (N
      = 21), b) increase with other symptoms of recurrent disease (N = 45), c)
      increased levels as early symptom of recurrent disease (N = 37). 30 patients
      (9.8% of all patients with recurrent disease; 2.3% of all patients) with
      increased CEA levels at the time of recurrent disease underwent surgical
      resection with curative intention (R0 resection). CONCLUSIONS: Our findings
      indicate that up to 47% of the patients with recurrent disease and 11% of all
      patients (N = 144, groups IIa + IIIb + IIIc) could benefit from routine follow-up
      CEA determinations after curative colorectal cancer resection. Nonetheless, only
      2.3% of all patients with elevated CEA levels underwent R0 resection of recurrent
      disease. Despite these detection and R0 resectability rates, CEA plays a crucial
      role in the early detection of recurrent disease and remains an important part of
      routine patient care after curative resection of colorectal cancer.

PMID- 11326644
TI  - A comparison of serum and tissue hCG beta as prognostic markers in colorectal
      cancer.
AB  - BACKGROUND: Production of the glycoprotein hormone hCG beta has been associated
      with aggressive behavior in nontrophoblastic tumors. In this study the prognostic
      value of serum level and tissue expression of hCG beta were compared in 232
      patients with colorectal cancer. MATERIALS AND METHODS: Serum levels were
      measured with a hCG beta specific immunofluorometric assay. Tissue specimens were
      stained with the same monoclonal antibody as in the serum assay. RESULTS: The
      proportion of patients with a positive immunohistochemical expression of hCG beta
      was higher (22%) than the proportion with elevated serum levels (17%). The
      correlation between serum and tissue expression was moderate (kappa 0.298). Both
      serum and tissue expression of hCG beta were independent prognostic factors. hCG
      beta serum level was a stronger prognostic factor than tissue expression both in
      uni- and in multivariate analysis. The accuracy when predicting 5-year survival
      status of the patients was highest (63%) when using the combined results of serum
      and tissue expression. CONCLUSIONS: There is a moderate correlation between hCG
      beta expression in serum and in tissue. The predictive accuracy of serum hCG beta
      was higher than the predictive accuracy of tissue expression, and the prognostic
      accuracy was further slightly increased when using a combination of tissue and
      serum expression.

PMID- 11326646
TI  - Improved sensitivity of fuzzy logic based tumor marker profiles for diagnosis of
      pancreatic carcinoma versus benign pancreatic disease.
AB  - BACKGROUND: The definite diagnosis of pancreatic tumors of unknown origin remains
      a clinical challenge. Imaging techniques may fail to differentiate malignant
      tumors from inflammation, especially in chronic pancreatitis. In a considerable
      number of cases, the definitive diagnosis needs laparotomy. Single tumor markers
      as CA 19-9 or CEA are of limited value in these cases because of their limited
      sensitivity and specificity. This study was performed to find out, whether a
      classification method based on fuzzy logic analysis of tumor marker profiles is
      feasible in patients with pancreatic carcinoma and benign pancreatic disease.
      PATIENTS AND METHODS: Tumor markers and other clinical and laboratory parameters
      of 74 consecutive patients, either with histologically proved pancreatic
      carcinoma (n = 43) or presumed benign pancreatic disease (n = 31) assessed by
      ultrasound, endoscopic retrograde pancreatography, or computed tomography were
      analysed in order to detect their diagnostic value in the multi-dimensional
      approach of fuzzy logic analysis. RESULTS: Given a specificity of 95%,
      sensitivity was considerably increased by the fuzzy logic method (83%) compared
      with the best single tumor marker CA 19-9 (65%). CA 19-9, CYFRA 21-1 and CA 15-3
      gave the most considerable contributions to the classification system, whereas
      CEA, CA 125, CA 72-4, AFP, liver enzymes, lipase, amylase, bilirubin, and
      ferritin were of no or little value. CONCLUSIONS: Tumor marker profiles analysed
      with the fuzzy logic method may have an improved sensitivity compared with single
      standard tumor markers. The diagnostic efficacy should be proved in patients with
      pancreatic tumors of unknown origin.

PMID- 11326647
TI  - The tumor marker tumor M2-PK: an application in the diagnosis of gastrointestinal
      cancer.
AB  - The present study is designed to evaluate the use of the tumor marker Tumor M2-PK
      in the discrimination between gastrointestinal (Gl) cancer patients and patients
      with non malignant gastrointestinal diseases. The concentration of Tumor M2-PK
      was analyzed in EDTA-plasma of 413 Gl cancer-patients and 141 patients with non
      malignant diseases. The test resulted in a highly significant discrimination (p <
      0.001) of tumor patients and controls. The diagnostic specificity was 89%. A
      diagnostic sensitivity between 48% and 73%, depending on the different tumor
      entities (colorectal cancer, gastric cancer, oesophageal cancer and pancreatic
      cancer), was observed. These sensitivities were generally higher when compared
      with those of the established tumor markers CEA, CA 19-9 and CA 72-4, with the
      exception of CA 19-9 in pancreatic cancer. A combination of Tumor M2-PK with the
      appropriate first choice-marker (e.g. CEA + Tumor M2-PK for colorectal cancer)
      resulted in a remarkable increase in the sensitivities.

PMID- 11326648
TI  - Tumor M2-pyruvate kinase: a promising tumor marker in the diagnosis of gastro
      intestinal cancer.
AB  - The diagnostic value of pyruvate-kinase type tumor M2 (Tumor M2-PK) has been
      investigated in different tumors, and showed interesting results in cases of
      renal cancer, pancreatic cancer, lung cancer and some cases of gastric cancer. In
      this study we investigated EDTA-plasma of 68 patients with gastrointestinal
      cancer, 22 patients with inflammatory bowel disease (IBD) and 60 healthy
      controls. Sensitivity of Tumor M2-PK was 70.6% for all GI-tumors, that of CA19-9
      was 55.4% and that of CEA was 53.3%. In pancreatic cancer CA19-9 showed the best
      sensitivity. In oesophageal/gastric cancer Tumor M2-PK was most sensitive and in
      colorectal cancer CEA and Tumor M2-PK showed the best results. The specificity of
      Tumor M2-PK was 90-96, 7%. In IBD some individuals showed elevated Tumor M2-PK
      levels but there was no correlation to CRP or to the clinical activity score. The
      results indicated that Tumor M2-PK might be a valuable marker in gastrointestinal
      cancer.

PMID- 11326649
TI  - Radical prostatectomy: survival outcome and correlation to prostate-specific
      antigen levels.
AB  - BACKGROUND: This paper reviews a 10-year experience with radical retropubic
      prostatectomy (RP) focussing on survival outcome related to pre- and
      postoperative levels of prostate-specific antigen (PSA). PATIENTS AND METHODS:
      739 patients who underwent RP between 1987 and 1998 were prospectively
      investigated. Kaplan-Meier analyses were performed and correlated to pre- and
      postoperative PSA concentrations. RESULTS: In a follow up period of 11 years
      duration, (mean 3 yrs.) 57 of 739 patients died (20 from prostate disease
      progression, 37 from other causes). Correlation between low pre-operative PSA and
      pathological organ-confinement was significant (p < 0.001). Of 175 patients with
      PSA progression, 53 (30%) had never reached undetectable levels of PSA. 57% of
      PSA relapses were detected during the first year, and 3% later than 5 years post
      operatively. Kaplan-Meier analysis yielded an average 3 years advantage in
      estimated prostate-cancer-specific survival when pre-operative PSA levels were
      below 50 ng/ml. Overall, prostate-cancer-specific and PSA-free 5-year survival
      rates were 88%, 96% and 67% respectively. CONCLUSIONS: Survival-rates after RP
      are high even in conjunction with unfavourable PSA outcome. Merely one third of
      deaths resulted from prostate cancer, since men at risk frequently suffer from
      concomitant diseases that affect survival.

PMID- 11326650
TI  - Hepatic arterial infusion with oxaliplatin, folinic acid, and 5-fluorouracil in
      patients with hepatic metastases from colorectal cancer: role of carcino
      embryonic antigen in assessment of response.
AB  - BACKGROUND: Therapy for patients with hepatic metastases from colorectal cancer
      (CRC) remains controversial and may be improved by regional oxaliplatin which
      proved to be effective when administered systemically to patients with advanced
      CRC. METHODS: During the current study, which aims to determine the maximum
      tolerated dose, the dose-limiting toxicity, and the pharmacokinetics of
      oxaliplatin applied as hepatic intra-arterial infusion combined with folinic acid
      and 5-fluorouracil in patients with hepatic metastases from CRC, serial levels of
      carcino-embryonic antigen were determined and their relationship to response to
      therapy was assessed. RESULTS: Toxicity mainly consisted of nausea, pain,
      mucositis, sensorial neuropathy, diarrhoea, and thrombocytopenia. The results of
      tumor marker analyses suggest that progressive disease may be detected early by
      increasing CEA levels and responsive disease may be characterized by low or
      decreasing values. CONCLUSIONS: Further analyses are warranted to determine the
      role of CEA in the assessment of response as compared to imaging techniques.

PMID- 11326651
TI  - Altered prostate specific antigen reference range after transurethral resection
      of the prostate.
AB  - OBJECTIVES: We investigated how transurethral resection of the prostate (TURP)
      affected the serum concentration of prostate specific antigen (PSA) and whether
      the reference range for PSA has to be altered in these patients following TURP.
      METHODS: 55 patients were retrospectively analysed. All had undergone TURP for
      bladder outlet obstruction due to benign prostatic hyperplasia which was
      confirmed by histopathological amination. PSA was determined pre-operatively and
      postoperatively every 6 months for 48 months. These patients were compared to 12
      patients who had undergone radical perineal prostatectomy (RPP) for prostate
      cancer (CaP). In the latter group, in all patients a TURP had been performed up
      to 7 years before CaP was diagnosed. RESULTS: The median PSA concentration was
      4.9 ng/ml before TURP and was subsequently reduced to 0.6 ng/ml after 48 months.
      There was a steady decrease of the PSA concentration during the observation
      period. In contrast in patients who subsequently developed a CaP, the median PSA
      concentration before TURP was 6.8 ng/ml and was reduced to only 2.2 ng/ml after
      48 months. PSA levels started to rise before CaP was diagnosed. CONCLUSION: After
      a TURP with a benign histopathologic specimer) PSA levels decrease steadily to
      values below 2 ng/ml. In case these patients demonstrate a rising PSA in the
      follow-up after partial prostatectomy, a CaP should be ruled out.

PMID- 11326652
TI  - Are age-specific reference ranges for prostate specific antigen population
      specific?
AB  - INTRODUCTION: At present PSA is Considered to be the leading screening test for
      prostate cancer. We determined whether in men 60 to 79 year old with a serum
      prostate specific antigen (PSA) within age specific PSA reference ranges prostate
      biopsy could be safely eliminated. METHODS: We retrospectively analysed all 60-79
      year old men who had undergone radical perineal prostatectomy (RPP) for prostate
      cancer (CaP) at our institution. All patients had undergone prostate biopsy
      following an abnormal rectal examination and/or PSA greater than 4.0 ng/ml. We
      compared our results using the standard reference range of 0 to 4.0 ng/ml with
      those we had obtained using the age specific PSA reference ranges of Oesterling
      et al. RESULTS: 204 men between 60-69 years and 67 men between 70-76 years had
      undergone RPP for CaP. Applying age specific PSA reference ranges 56 CaP would
      have been overlooked. Of those 46% had a favourable histology. Taken together 54%
      of the cancers overlooked had an unfavourable histology. CONCLUSION: In contrast
      to previous reports of unfavourable histological characteristics in only 5-24% of
      missed cancers, applying age specific PSA reference ranges, 54% of missed cancers
      in our patients exhibited an unfavourable histology. We therefore conclude that
      age specific PSA reference ranges did not safely eliminate the need for prostate
      biopsy in our study population.

PMID- 11326653
TI  - Prostate specific antigen in as a dynamic model in advanced prostate cancer.
AB  - BACKGROUND: Prostate specific antigen doubling time (PSADT) is a prognostic
      factor after radical prostatectomy, radiation therapy, and hormonal therapy
      respectively for prostate cancer. However, its role in patients receiving
      chemotherapy has not been evaluated to date. PATIENTS AND METHODS: Thirty
      patients (pts.) with hormone resistant prostate cancer were enrolled in a
      prospective phase II study to receive oral Idarubicin. The drug was administered
      at a dose of 35 mg on day 1 and 8 of each cycle, and treatment was repeated every
      3 weeks. RESULTS: Fully evaluable for response were 26 pts. 13 of these 26 had
      measurable disease and 3 out of 13 had no change (NC) after therapy. Ten pts. had
      progression. All 13 pts. with non-measurable disease showed no response. PSA
      values increased exponentially over time in all pts., except for the 3 pts. with
      NC, in whom PSA values remained stable. Median PSADT of pts. with a rising PSA
      was 2.1 months (mean 2.6; range 0.7-6.1). CONCLUSIONS: PSA levels in pts. not
      responding to treatment with Idarubicin rose in an exponential fashion similar to
      pts. who were only on hormonal therapy. PSADT should be evaluated in a larger
      number of hormone resistant prostate cancer pts. as a possible surrogate
      endpoint.

PMID- 11326654
TI  - Prostate-specific antigen (PSA) in the monitoring of prostate cancer after
      radical prostatectomy and external beam radiation.
AB  - BACKGROUND: During the last few years, prostate-specific antigen (PSA) has been
      established as the most important tumor marker for prostate cancer. The aim of
      our study was to evaluate the response of PSA after surgery and radiotherapy of
      prostate cancer. PATIENTS AND METHODS: From 1/1995 to 9/1997, 32 patients were
      treated by radical prostatectomy and subsequent radiotherapy. Radiation therapy
      was carried out using a linear accelerator to the prostate bed, a total dose of
      60 Gy was given. PSA values were measured immediately before irradiation, weekly
      during radiation therapy and every three months thereafter in the usual follow-up
      pattern. RESULTS: 21 of 32 patients had no measurable PSA after surgery. In the
      remaining 11 patients the median PSA half-life was reached 3 months after
      irradiation, the nadir after 15 months. 5 patients with increasing PSA levels
      suffered from a relapse (15.6%). CONCLUSIONS: We found that PSA monitoring is a
      useful marker for treatment outcome and that adjuvant radiotherapy after surgery
      improves local control as well as biochemical failure rate. If PSA is still
      detectable after surgery the risk for biochemical failure is significantly higher
      (45.5%).

PMID- 11326655
TI  - The behavior of prostate specific antigen (PSA) and free-PSA (f-PSA) under
      antihormonal therapy.
AB  - Within a few weeks, if therapy of the hormone sensitive, advanced prostate cancer
      (PCa) is sufficient, there will be a PSA-decrease to testify to the regression of
      the PCa. Free-PSA (f-PSA) is used for the differential diagnosis of the PCa.
      Values under 25% f-PSA in proportion to complete-PSA show the possibility of the
      existence of a Pca. The aim of the work was to study the behavior of f-PSA under
      hormonal ablation. Initial PSA and f-PSA was examined (RIA) in 76 patients
      (average age = 72.8 yrs. old) with advanced PCa. (metastases) proven by bone
      scintigraphy and/or computed tomography. During hormonal therapy (LHRH-agonists)
      monthly PSA and f-PSA abundance were examined. The percent amount of f-PSA was
      calculated and documented for at least 6 months. The initial PSA-values were 43.6
      +/- 17.3, the f-PSA were 13.4% +/- 8.9. Under antihormonal therapy PSA decreased
      (while f-PSA increased) and after a period of 1 month the values were 27.4 +/-
      14.9 (17.4% +/- 12.3), after 3 months 18.1 +/- 11.3 (24.5% +/- 9.9), after 6
      months 7.9 +/- 6.8 (26.1 +/- 10.6). During the 6 months of hormonal ablation PSA
      values continuously declined, while, after the first 3 months, f-PSA-values
      showed a behavior similar to benign hyperplasia of prostate. The therapeutic
      efficiency of the antihormonal therapy is clearly shown through f-PSA and PSA.
      There are no timely advantages between the two markers. Further investigations
      will show whether hormone insensitive PCa can be recognized quicker through f-PSA
      than from an increase in PSA.

PMID- 11326656
TI  - Serum-to-urinary prostate-specific antigen ratio in patients with benign
      prostatic hyperplasia and prostate cancer.
AB  - BACKGROUND: Prostate-specific antigen (PSA) is the single most important tumor
      marker in early detection and monitoring of prostate cancer (CaP). However,
      routine analysis of serum PSA concentrations does not allow differentiation
      between CaP and prostatic diseases. The aim of the present study was to evaluate
      the usefulness of the serum-to-urinary PSA ratio in a clinical setting. MATERIALS
      AND METHODS: In a retrospective clinical study, we determined serum and urine PSA
      concentrations in 48 patients with benign prostatic hyperplasia (BPH) and 57
      patients with histologically confirmed CaP. RESULTS: The serum-to-urinary PSA
      ratio is able to discriminate BPH from CaP. CONCLUSIONS: Determination of the
      serum-to-urinary PSA ratio enhances the specificity of PSA in screening for CaP
      and monitoring of patients with CaP under androgen deprivation therapy.

PMID- 11326657
TI  - Ratio of alpha 1-antichymotrypsin--prostate specific antigen to total prostate
      specific antigen in prostate cancer diagnosis.
AB  - OBJECTIVE: To evaluate the analytical performance and diagnostic utility of
      prostate specific antigen (PSA) bound to alpha 1-antichymotrypsin (ACT) in serum
      to improve the differentiation between benign prostatic hyperplasia (BPH) and
      prostate cancer (PCa). METHODS: A total of 351 white men 21 to 88 years old were
      analysed. Serum concentration of tPSA, free PSA (fPSA) and ACT-PSA were measured
      in 163 untreated PCa patients (median age 66 years), 94 patients with
      histologically or clinically confirmed BPH (median age 65 years) and 94 men
      without prostate disease considered as controls (median age 54 years). The
      Elecsys system 2010 (Roche Diagnostics, Germany) was used for the determinations
      of tPSA and fPSA. The ACT-PSA assay is a new developed prototype on the ES system
      (Roche Diagnostics, Germany). RESULTS: The ACT-PSA assay showed reliable data of
      analytical performance in comparison to established assays for tPSA and fPSA. The
      median concentrations of tPSA (PCa: 9.22 micrograms/L, BPH: 2.28 micrograms/L,
      controls: 0.99 microgram/L) and ACT-PSA (7.99 micrograms/L vs. 1.63 micrograms/L
      vs. 0.58 microgram/L) were significantly different, respectively. The median
      ratios of fPSA/tPSA (PCa: 12.3%, BPH: 25.4%), ACT-PSA/tPSA (90.5% vs. 66.6%) and
      fPSA/ACT-PSA (14.0% vs. 38.6%) were significantly different between PCa and BPH
      patients. Significant differences of ratios between BPH and controls were not
      observed. Receiver operating characteristics analysis (tPSA up to 20
      micrograms/L) for discrimination between PCa and BPH showed that the ratios
      fPSA/tPSA (area under the curve: 0.861) and fPSA/ACT-PSA (0.847) were
      significantly different from tPSA (0.663), but ACT-PSA (0.733) alone and also the
      ratio of ACT-PSA/tPSA (0.780) were not significantly different from tPSA (0.663).
      CONCLUSION: The ratio fPSA/tPSA showed the best discrimination between BPH and
      PCa. The single or additional determination of ACT-PSA to tPSA does not improve
      the differentiation between the two groups of patients.

PMID- 11326658
TI  - Tissue polypeptide specific antigen serum concentrations in patients with newly
      diagnosed prostatic diseases.
AB  - Recently, tissue polypeptide specific antigen (TPS), a cytokeratin 18 marker, was
      described to be discriminative between cancer of the prostate (CaP) and benign
      prostatic hyperplasia (BPH). In our study we investigated the ability of the TPS
      serum concentration as a staging marker in patients with newly diagnosed CaP.
      METHODS: Serum levels of TPS and PSA were determined in patients with newly
      diagnosed, untreated CaP (pT1-3pNoMo: n = 71; T1-4NxM+: n = 39) and BPH (n = 30).
      The TPS serum concentration was correlated to the PSA serum concentration.
      RESULTS: Median TPS concentration was 33.6 U/L in the pT1-3pNoMo-group; 113.5 U/L
      in the Tl-4NxM(+)-group and 59.7 U/L in the BPH-group. Although the TPS
      concentration failed to discriminate between patients with localized CaP and BPH,
      it discriminated very well between patients with (M+) and without (Mo) bone
      metastases (p < 0.001). Furthermore no correlation with PSA levels could be
      established. CONCLUSION: The TPS serum concentration seems to provide additional
      information in the initial staging of patients with newly diagnosed untreated
      CaP.

PMID- 11326659
TI  - Distribution of collagens in carcinomas of salivary and mammary gland origin in
      irradiated rats.
AB  - OBJECTIVE: While radiation-induced sarcomas or carcinomas following chemical
      carcinogens are well-documented in rats, radiation-induced carcinomas, especially
      adenoid-cystic carcinomas (ACC) and adenocarcinomas, originating from the head
      and neck region, including the major salivary glands (SG) are rarely reported.
      Because in human ACC of the SG structural changes of the basement membrane (BM)
      with positive correlation of tumor differentiation loss and BM thinning have been
      described, this study set out to analyze collagen distribution in malignant rat
      tumors (TM) developing inside the radiation field (RF) and spontaneously. The TM
      arose in the course of studies on other questions regarding radiation effects
      following fractionated radiation (2 Gy/day, 5 times a week; total dose 60 Gy).
      METHODS: We investigated 22 TM (14 malignant, 8 benign) of 22 female Wistar rats.
      The RF comprised the left head and neck area. Besides assessment of hematoxylin
      eosin (HE)-stained sections collagens (C; types III and IV) were investigated
      using immunohistochemical methods. RESULTS: Nine malignant TM originated from the
      SG, a further three from the milk line and two from the maxilla. Two ACC, two
      cystadenocarcinomas, one microcystic adenocarcinoma and four squamous cell
      carcinomas (SCC) arising from the SG (one SCC was observed in the maxilla)
      developed in the RF. One microcystic adenocarcinoma, one ACC and one
      adenocarcinoma with sebaceous differentiation arising from the milk line and one
      SCC arising from the maxilla were found in non-irradiated animals. As typical
      results, in the ACC (glandular subtype), C III was detected in the interstitium
      with sometimes stronger staining surrounding myoepithelial cells (MC) and
      excretory duct structures (ECD). Weak C IV staining in a string-like fashion was
      found in ECD and MC. In larger pseudocysts the lumen contained substances
      reacting with C IV antibodies. In the cystadenocarcinomas and the microcystic
      adenocarcinomas reactions at variable levels after anti-C III incubation were
      found close to modified MC and ECD with transition to the interstitium. C IV was
      more intensely stained in these entities, in part continuously and with
      broadening around MC and ECD. However, especially in more anaplastic parts of the
      tumor, fragments, interruptions or loss of the BM were noted. Focal interstitial
      immunoreactivity, e.g. conglomerates, was also identified. CONCLUSION: In rat
      carcinomas collagen detection was partially of a continuous layer, even with BM
      thickening and more extended deposition. In contrast, BM fragmentation or loss
      was displayed more often in anaplastic parts of the tumor. Also, the interstitium
      showed conglomerated collagen formations. Therefore, the increasing loss of BM in
      rat SG tumors is similar to that in humans and in both species is a sign of
      dedifferentiation.

PMID- 11326660
TI  - Molecular genetic methods in the diagnosis of invasive bladder cancer.
AB  - Development and progression of tumours is generally driven by an accumulation of
      genetic alterations. In this study we correlated chromosome 17 aneuploidy to
      invasiveness of bladder cancer by the method of fluorescence in situ
      hybridisation (FISH) in urinary cytospins. We investigated the value of FISH
      compared to DNA cytophotometry in the diagnosis of bladder cancer. 39 patients
      with or suspicious for bladder tumour were analyzed. 19 patients had a bladder
      tumor at the time of diagnosis, 14 superficial (Ta-T1) and 5 invasive (T2-3). The
      remaining 20 patients had no tumour at the time of diagnosis, however 9 of them
      had one in prehistory (Ta-T2). For FISH we used the DNA probe of HER-2/neu
      located on chromosome 17. DNA image cytometry was performed according to single
      cell interpretation of Bocking. Our results showed a correlation between HER
      2/neu CEP 17 alterations and invasive bladder cancer to the extent of 10-70%
      aberrant cells for patients with current invasive bladder tumour as well as for
      patients who had been cured but with as invasive bladder cancer in prehistory. On
      the other hand, the percentage of aneuploid cells for negative biopsy and
      superficial tumour was 0-2%. The DNA cytophotometry brought an uniform aneuploidy
      only for present invasive tumours: negative biopsies, superficial cancer and
      invasive tumour just in prehistory, showed mixed diploid-aneuploid DNA patterns.
      Our results showed that for the detection of aberrant tumour cells the method of
      FISH is more sensitive than DNA cytometry. FISH could provide important
      information in the prognosis of bladder cancer.

PMID- 11326661
TI  - Immunohistochemical examinations (Ki67, p53, nm23) and DNA cytophotometry in
      bladder cancer.
AB  - Bladder cancer is clinically characterized by a high recurrence rate for
      superficial tumours up to 70% and by the invasiveness of advanced bladder cancer.
      To learn more about the biological behaviour of an individual bladder cancer
      different tumour markers have been investigated. The aim of our study was to
      compare the potential of aggression of both superficial and invasive bladder
      tumours by means of the proliferation marker Ki67, the tumour suppressor gene
      p53, the non metastasizing protein nm23 and the evaluation of DNA ploidy. We
      examined 36 patients, 28 with a bladder tumour (Ta-T4) and 8 without as a control
      group. For immunohistochemistry (Ki67, p53, nm23) we took paraffin sections and
      scored semiquantitatively under a microscope. The DNA cytophotometry was done on
      bladder washings by evaluating the DNA ploidy of single cells. The results showed
      that benign tissues were negative for Ki67 and p53 but positive for nm23. The DNA
      diagnosis was diploid for all benign samples. The superficial bladder cancer (Ta,
      T1) showed, in comparison to the invasive tumours, significantly lower numbers of
      aneuploid cells and a higher rate of p53 mutations. On the other hand the
      invasive tumours (T2-4) were correlated to significantly higher proliferation
      rates and higher potencies for metastasizing. The combination of the investigated
      tumour markers allowed a graduation of the biological behavior of an individual
      bladder cancer. Especially a high p53 mutation rate and a non aneuploid DNA
      diagnosis were indicators for the recurrence of superficial bladder tumours.
      Invasive growth of bladder cancer was characterized by high Ki67 proliferation
      and low nm23 protein binding.

PMID- 11326662
TI  - Tu-M2-PK in the blood of testicular and cubital veins in men with testicular
      cancer.
AB  - We wanted to verity whether M2-PK is a useful marker in testicular cancer. In a
      prospective study of 20 consecutive patients, blood was drawn from the testicular
      and the cubital vein before semicastration and later. For the detection of M2-PK
      we used the Assay of ScheboTech. In the testicular vein M2-PK was 11.2 U/ml. In
      the cubital vein it was 6.2 U/ml before semicastration, increasing in the
      following days. There were no significant differences between testicular and
      cubital vein blood, between the non-metastasized patients and the metastasized
      stages and between the patients with seminoma and non-seminomatous tumors. There
      is no profit in the diagnosis of testicular cancer using Tu-M2-PK.

PMID- 11326663
TI  - CYFRA 21-1, TPA-M, TPS, SCC-Ag and CEA in patients with squamous cell lung cancer
      and in chemical industry workers as a reference group.
AB  - In etiology of lung cancer chemical carcinogenesis seems to be a very important
      factor. In the studies presented here the diagnostic usefulness of tumor markers
      in lung cancer was evaluated, using as a reference group workers of a chemical
      plant producing chromite and chromate pigments. The investigations of CYFRA 21-1,
      TPA-M, TPS, CEA and SCC-Ag were performed before treatment in a group of 76
      squamous cell lung cancer patients in different stages of disease and in a
      reference group of 75 workers of the chemical company, who had been exposed to
      hexavalent chromium for longer than 1 year and had no clinical or radiological
      symptoms of lung diseases. In the squamous cell lung cancer group concentrations
      of all analyzed tumor markers were considered to be significantly higher than in
      the reference group. TPA assay demonstrated higher diagnostic performance than
      CYFRA 21-1 and the remaining tumor markers. At 0.95 specificity, the sensitivity
      of TPA was 0.79, CYFRA 21-1 -0.76, of TPS -0.29 whilst of CEA and SCC-Ag -0.31.
      The univariate analysis showed a significant prognostic value for clinical
      stages, only for CYFRA 21-1 and SCC-Ag. A significant relationship between marker
      level and survival was observed for CYFRA 21-1 as well as SCC-Ag levels. In a
      multivariate analysis CYFRA 21-1 and/or TPS remained significant predictors of
      survival.

PMID- 11326665
TI  - Co-localization of CD44 and urokinase-type plasminogen activator on the surface
      of human melanoma cells.
AB  - Adhesion and proteolysis are basic reactions of tumor growth and metastasis.
      During these complex processes malignant cells change their adhesion behaviour
      and proteolytic capacity. Therefore, an extensive characterization of tumor cells
      is necessary if results of functional assays e.g., tests for tumor cell invasion
      are to be correlated with the presence of tumor antigens. This paper describes
      the detection of CD44 variant sequences, urokinase-type plasminogen activator
      (uPA) and uPA-receptor (uPAR) by immunoluminescence and activity measurements.
      For these investigations the melanoma cell line IGR 1 was used. The expression of
      CD44 (v5), uPA and uPAR on the cell surface was shown by indirect labelling with
      monoclonal antibodies (mAb). The marker enzyme horseradish peroxidase (HRP) of
      the secondary Ab was used to release luminescence and fluorescence with suitable
      substrates. The enhanced luminescent assay was superior to fluorescence analysis.
      uPA-activity in intact cells was examined with the substrates plasminogen, Z-Gly
      Gly-Arg-AMC and Z-Lys-SBzl including selective inhibitors. The immunoluminescent
      assay can be alternatively used with well-tried immunofluorescent methods e.g.
      flow cytometry, for the detection of cellular cancer markers (1).

PMID- 11326664
TI  - MIA as a reliable tumor marker in the serum of patients with malignant melanoma.
AB  - BACKGROUND: Reports published in 1996 concerning the protein MIA proposed it as a
      useful tumor marker for patients suffering from malignant melanoma. Therefore we
      systematically started to measure MIA levels in patients with malignant melanoma.
      It was and still is questionable whether MIA in the serum of melanoma patients is
      a reliable tumor marker in terms of course of disease, therapy-monitoring and
      prognostic value. Previous studies have already confirmed the specifity of MIA as
      a tumor marker for malignant melanoma. MATERIALS AND METHODS: Using an ELISA-
      System, we examined over 830 blood samples of 326 melanoma patients. The cut-off
      was determined at 9.8 ng/ml. RESULTS: 5.6% (n = 17) of melanoma patients at stage
      I/II (n = 302) showed increased MIA levels, whereas at stage III/IV (n = 5/n =
      19) high levels were found in 60.0% and 89.5% respectively. Patients at stage
      III/IV with MIA levels below the cut-off turned out to be the ones after
      metastatic surgery, irradiation or chemotherapy. None of these patients developed
      further metastases during follow-up, just as patients at stage I/II without
      increased MIA levels. After a distinct rise of MIA levels, metastases could be
      detected at the same time or shortly after. On the other hand we saw decreasing
      levels after or during therapy. CONCLUSION: Our data showed that MIA is a
      suitable serum marker to detect metastases and to monitor course and therapy of
      disease. The prognostic value (increased MIA levels at stage I/II), however,
      requires further investigation.

PMID- 11326666
TI  - Tumor associated glycoprotein (TAG) 12: a new tumor marker in breast cancer.
AB  - We compared the preoperative sensitivity of tumor associated glycoprotein (TAG)
      12 of 128 primary breast cancer patients with the established tumor marker CA 15
      3 and received a similar, even slightly higher sensitivity. In the follow-up the
      first results showed in some cases different courses of Tag 12 values especially
      in cases without expression of CA 15-3 whilst in some cases we found an earlier
      response of TAG 12 to a progression of the disease.

PMID- 11326667
TI  - Comparison of the tumor markers tumor M2-PK, CEA, CYFRA 21-1, NSE and SCC in the
      diagnosis of lung cancer.
AB  - The study presents data comparing the new tumor marker Tumor M2-PK with CEA,
      CYFRA 21-1, NSE and SCC in the diagnosis of lung cancer. Tumor M2-PK is
      quantitatively detectable in EDTA-plasma with a sensitive ELISA. The results of
      the tumor marker test were compared with respect to the different histological
      tumor types and with the tumor staging. So far 144 newly diagnosed lung cancer
      patients were included. Significantly elevated tumor marker concentrations were
      found with progressive tumor stages. The best correlation with the tumor stage
      was observed for Tumor M2-PK and CYFRA 21-1. Comparison of the sensitivities in
      the detection of lung cancer indicated that the Tumor M2-PK-test (sensitivity:
      58%) is more efficient than the CEA-Test (sensitivity: 39%) or CYFRA 21-1
      (sensitivity: 48%). Generally higher sensitivity for non-small cell lung cancer
      only was shown for Tumor M2-PK (sensitivity: 65%), CEA (sensitivity: 42%) and
      CYFRA 21-1 (sensitivity: 58%). For small-cell lung cancer the marker NSE was more
      sensitive than all other markers. Initial follow-up studies indicate that Tumor
      M2-PK and CYFRA 21-1 can be used to monitor disease with tumor progression or
      regression during chemotherapy. The present data indicated that Tumor M2-PK could
      be a valuable tumor marker for the detection of lung cancer.

PMID- 11326668
TI  - Comparative study on the clinical use of protein S-100B and MIA (melanoma
      inhibitory activity) in melanoma patients.
AB  - BACKGROUND: The guidelines for the care of melanoma patients have not recommended
      the routine use of tumor markers up till now. In comparison to the blood
      parameters, two serum proteins have demonstrated their usefulness in the follow
      up of melanoma patients: protein S-100B, a member of the S100 protein family, and
      "Melanoma-inhibitory activity" (MIA), a recently described 11 kd soluble protein.
      We analysed the serum levels of S-100B and MIA in non-melanoma control patients
      and in melanoma patients in different stages of disease (stage I-IV) to report on
      the sensitivity and specificity of both tumor markers. PATIENTS AND METHODS: The
      serum concentration of S-100B was evaluated by a luminoimmunometric assay (LIA)
      in 670 blood samples of 87 melanoma patients and, as controls, in 169 blood
      samples of patients with different skin diseases apart from melanoma. MIA serum
      levels were measured by an enzyme-linked immunoassay (ELISA) in 791 serial blood
      samples of 87 melanoma patients and in 158 blood samples of control patients. A
      cut-off of 0.12 microgram/l (S-100B) and 6.5 micrograms/l (MIA) served as upper
      normal values in the melanoma group as recommended by the producing industrial
      companies. In the control patient group, we additionally used the cut-off value
      of 0.2 microgram/l for S-100B and 8.5 micrograms/l for MIA, respectively.
      RESULTS: In stage I/II 37.5%, in stage III 50% and in stage IV 80% of the blood
      samples were S-100B positive (> or = 0.12 microgram/l) prior to treatment. Post
      treatment (after complete surgery) S-100B was below the cut-off value in stage
      I/II 83.9%, in stage III 82% and in stage IV 85.7%, respectively. For MIA we
      found in stage I/II 0%, stage III 53.8% and in stage IV 68.3% of the blood
      samples positive (> or = 6.5 micrograms/l) prior to treatment. Post treatment:
      stage I/II 88.3%, stage III 90.3% and stage IV 93.1% were below the cut-off
      value. In the control group we found 85.8% and 89.9% of the blood samples beneath
      the cut-off values for S-100B and MIA, respectively. CONCLUSION: We were able to
      identify the majority of patients with advanced metastatic melanoma by analysing
      the serum levels of S-100B and MIA. The specificity of both tumor markers was
      within acceptable limits. However, the available data suggest that a slightly
      higher cut-off value might be of clinical value.

PMID- 11326669
TI  - Soluble p185/her2 and S100 in yolk sac blood from human melanoma metastases
      xenotransplanted to chick embryo chorioallantoic membrane.
AB  - BACKGROUND: The chorionallantoic membrane (CAM) of the chick embryo has been used
      as an experimental model for studying tumor invasion and metastasis of human
      malignant melanoma. In search for a model to show graft-host-interactions in
      vivo, tumor markers in peripheral blood of the host were investigated. MATERIALS
      AND METHODS: Before collecting melanoma metastasis xenografts, blood samples were
      taken from CAM and a control group. S100 and sp185/her2 in peripheral blood were
      evaluated in a blinded manner. RESULTS: 23/28 samples deriving from successfully
      performed human melanoma metastasis CAM xenografts were positive for S100 versus
      2/22 samples for sp185/her2. CONCLUSION: Regarding melanoma, in this model
      sp185/her2 gave no additional information. S100 levels corresponded to clinical
      and immunohistological findings concerning adherence of tumors and extravasation
      of human melanoma cells. Based on these data S100 levels in the peripheral blood
      could help to determine the effect of exogenous stimuli such as radiation and
      therapeutic agents on metastatisation of the xenografts.

PMID- 11326670
TI  - Lack of correlation between P53 expression, BCL-2 expression, apoptosis and ex
      vivo chemosensitivity in advanced human breast cancer.
AB  - The relationship between apoptosis and chemosensitivity remains complex. We
      tested the chemosensitivity of 45 patients with advanced breast cancer (BC) ex
      vivo against anthracyclines (A: doxorubicin, epirubicin), taxanes (T: paclitaxel,
      docetaxel), cisplatin (DDP) and CMF and any correlation with the expression of
      p53, Bcl-2 and apoptosis. Viable cells were processed for ex vivo ATP Tumor
      Chemosensitivity Assay (ATP-TCA). Immunohistochemistry was performed in
      corresponding tumor samples. Apoptosis prior to chemotherapy was assayed using a
      TUNEL Test. Of 45 BC tested, 18 (40%) were p53+ and 37 (82%) showed high Bcl-2
      expression. Apoptosis was detected in 29 (64.4%) specimens. The Ex vivo Response
      Rate (EVRR) for T was 75.6% in all cases. This was the highest rate among the 4
      drugs tested followed by CMF (66.7%). For A and DDP the positive rates were lower
      (27.6% and 10.6%, respectively). A significant correlation (r = 0.589, p < or =
      0.01) was found between tumors which were sensitive to A and DDP. There was no
      association between chemosensitivity and apoptosis. Moreover tests for p53 and
      Bcl-2 did not show a correlation to ex vivo chemosensitivity. Pretreatment
      apoptotic parameters are unlikely to predict the individual response of breast
      cancer to antineoplastic agents.

PMID- 11326671
TI  - Ex vivo assays to evaluate the role of protein kinase C in tumor cells of
      patients with breast cancer.
AB  - New anti-cancer strategies have been developed with respect to proteinkinase C
      (PKC) as a potential target for therapeutic intervention in patients with
      advanced breast cancer. Using cell lines, most of the preliminary data are
      encouraging but insufficient information is available concerning clinical breast
      cancer cells. Thus, we decided to clarify the involvement of PKC in clinical
      breast carcinoma cells. We isolated viable tumor cells from fluids or tissue
      burden of eleven patients with advanced breast cancer. Performance of short term
      cultures supplemented with commonly used antineoplastics mimicked the clinical
      situation. We determined the ex vivo chemosensitivity pattern of each cell
      population. Additionally, we analysed total PKC activity and quantified the PKC
      isoform eta. All assays showed a heterogeneous highly variable distribution of
      the data investigated. No tendency could be observed regarding the influence of
      the therapeutics on PKC activity, PKC-eta expression or chemoresistance,
      respectively. Moreover, changes in neither PKC-eta expression, PKC activity nor
      chemoresistance induced by a particular drug in an individual tumor necessarily
      predicted the same reaction in another tumor to this agent. Therefore, we
      concluded that more explorative data concerning this topic are required prior to
      the development of a clinically useful therapy regimen with PKC as the major
      target.

PMID- 11326672
TI  - Tumor type M2 pyruvate kinase expression in advanced breast cancer.
AB  - BACKGROUND: Recently, a high validity correlation of the tumor M2 pyruvate kinase
      (Tu M2-PK) isoenzyme in comparison to standard tumor markers has been
      demonstrated in solid tumors. We investigated this marker in 67 patients with
      advanced breast cancer (ABC) in comparison to healthy controls. MATERIALS AND
      METHODS: Plasma Tu M2-PK was measured using an ELISA assay (ScheBo Tech, Giessen,
      Germany) while serum CA27.29 was determined using a chemiluminescent immunoassay
      (Bayer Diagnostics, Tarrytown, USA). RESULTS: In a ROC analysis, the cut-off to
      discriminate patients from controls was established at 15 U/ml for Tu M2-PK
      (specificity 85%; positive predictive value 81%) and 30 U/ml for CA27.29
      (specificity 91%; positive predictive value 92%). Median ABC baseline levels
      (ranges) in patients with ABC for Tu M2-PK and CA27.29 were 12.8 U/ml (4.8
      252,495) and 130 U/ml (13.3-8130), respectively. Response assessment was done in
      45 chemotherapy courses of 38 pts. In 13 out of 19 blocks (68.4%) with PD
      (progressive disease), an elevated level of Tu M2-PK at baseline or in the follow
      up was found. In 17 out of 20 blocks (85%) with SD (stable disease), the Tu M2-PK
      level was normal at baseline or normalised within 4 weeks of treatment. All 6
      patients with disease remission had a normal baseline Tu M2-PK level or the
      levels decreased promptly. CONCLUSION: Tu M2-PK gives additional information
      about ABC, indicating disease activity and sensitivity to chemotherapy while
      CA27.29 reflects tumor burden.

PMID- 11326673
TI  - The correlation of c-erbB-2 oncoprotein and established prognostic factors in
      human breast cancer.
AB  - BACKGROUND: The c-erbB-2 (HER2/neu) receptor is a transmembrane
      phosphoglycoprotein associated with multiple signal transduction pathways. Its
      overexpression in breast cancer tissue has been correlated with poor prognosis.
      We report preliminary data of an ongoing study in invasive breast cancer patients
      exploring c-erbB-2 protein overexpression in relation to established tumor
      characteristics of prognostic value. MATERIALS AND METHODS: In primary breast
      carcinoma samples from 115 women undergoing surgery in our department in 1999, a
      polyclonal rabbit antibody to human c-erbB-2 oncoprotein was used for
      immunohistochemical assessment of the c-erbB-2 expression in formalin-fixed
      paraffin-embedded material. The data were statistically correlated with classical
      histopathological parameters. RESULTS: In the studied collective of mainly
      postmenopausal women (75%) with a high rate of early stage breast cancer (88% pT1
      + 2), there was no significant relation between c-erbB-2 overexpression,
      classified as positive in 42% of the samples, and lymph node involvement, tumor
      size and grade, or hormone receptor status. CONCLUSION: Using the presented
      highly sensitive method, no association between c-erbB-2 expression and
      established prognostic factors was found. These data are in line with reports
      that the value of HER2/neu determination is not fully clarified for the
      preadjuvant evaluation of newly diagnosed breast cancer patients.

PMID- 11326674
TI  - Use of TPS and CA 15-3 assays for monitoring chemotherapy in metastatic breast
      cancer patients.
AB  - TPS and CA 15-3 have been applied for monitoring treatment in patients with
      advanced breast cancer and the relationship between the initial marker levels and
      the changes of the markers during chemotherapy has been established. Both markers
      have demonstrated high sensitivity for detecting visceral and bone metastases in
      the patients (90-95%) compared to soft tissues and locally advanced disease (45
      50%). The marker combination, TPS and CA15-3, showed the highest sensitivity for
      detecting bone/visceral metastases (98%) and soft tissue/locally advanced
      metastases (75%). TPS showed a more frequent decrease in marker level (> 50%)
      compared to CA 15-3 as well as the highest correlation (68%) to the clinically
      confirmed events CR, PR compared to CA 15-3 (54%). In the subgroup of metastatic
      breast cancer patients, demonstrating increased marker levels (> 25%) during
      follow-up, TPS showed the highest correlation compared to the clinically
      confirmed progressive disease. In the subgroup of patients with clinically
      confirmed progression, contemporary measurements of the marker values resulted in
      correlation with the clinical findings in 78% for TPS and 58% for CA 15-3. TPS
      appears to be superior to CA 15-3 for follow-up of metastatic breast cancer
      patients. TPS and CA 15-3 marker increase preceded the clinical and/or
      radiological signs of distant metastases in most of the patients; 1.5 and 1.1
      months, respectively. The time elapsed between tumor marker increase and
      clinically confirmed progression was very short, which is also related to the
      frequent follow-up visits for metastatic breast cancer patients receiving
      chemotherapy. TPS appears to indicate the changes in the disease state earlier
      than clinical criteria or than the established tumor burden markers. The
      simultaneous determination of TPS and CA 15-3 provided additive information in
      advanced breast cancer patients and might guide management decisions in the
      individual patients.

PMID- 11326675
TI  - Value of tumor M2 (Tu M2-PK) in patients with renal carcinoma.
AB  - Pyruvate kinase is one of the glycolytic key enzymes. It exists in various
      isoforms which are expressed in different cell types. One of these isoforms, the
      type Tu M2-PK, is strongly overexpressed by tumor cells and released into body
      fluids. The concentration of Tu M2-PK in body fluids can be quantitatively
      determined by a commercially available enzyme-linked immunosorbent assay (ELISA)
      kit. The Tu M2-PK concentration was measured in EDTA-plasma of 116 patients with
      renal carcinoma and 42 patients suffering from nephritis, by using this kit. The
      ranges of the Tu M2-PK-concentrations of the two groups did not overlap,
      indicating a highly significant discrimination of renal carcinoma and benign
      renal diseases. Furthermore, the Tu M2-PK concentration in EDTA-plasma correlated
      strongly with the Robson tumor stage of the 116 patients. The present results
      indicated that the Tu M2-PK might be the first tumor marker, which could be an
      excellent complementation of the diagnostic program for renal carcinoma.

PMID- 11326676
TI  - A comparison of bone-related biomarkers and CA27.29 to assess response to
      treatment of osseous metastatic breast cancer.
AB  - BACKGROUND: The assessment of bone metastases by clinical examination or imaging
      techniques is still considered unreliable. We compared a specific marker of bone
      resorption, urinary deoxypyridinoline (DPD)-crosslinks, with serum calcium (Ca),
      alkaline phosphatase (AP) and CA27.29, to evaluate the status of bone metastases
      in patients with breast cancer. MATERIALS AND METHODS: Second morning voided
      urine was collected from 2 groups of patient (pts), those without evidence of
      disease (n = 118), and those with bone metastases (n = 85) under specific therapy
      plus pamidronate. DPD and CA27.29 were measured on the automated ACS180 system
      (Bayer Diagnostics, Tarrytown, NY, USA). Receiver operating characteristics (ROC)
      curves were established for each of the 4 biomarkers to determine whether they
      could distinguish the 2 subsets of pts with clinically sufficient validity, and
      to establish the corresponding cut-off values. RESULTS: Neither Ca nor AP was
      useful in discriminating the 2 subgroups. At a DPD cut-off of 13 nmol/mmol, we
      found a specificity of 69% and a sensitivity of 53% for diagnosing bone
      metastases. Best results, however, were seen for CA27.29. A cut-off value of 30
      U/ml resulted in a specificity of 62% and a sensitivity of 81%. CONCLUSIONS:
      CA27.29 was the best parameter for the discrimination of stage IV breast cancer
      with bone metastases. The primary advantage of DPD lies in the monitoring of bone
      metastases under specific therapy.

PMID- 11326677
TI  - Serum levels of CA 125 and TPS during treatment of ovarian cancer.
AB  - Two hundred and sixty ovarian cancer patients (including all FIGO stages) were
      enrolled in a prospective multicentre study. In this interim study we analyzed
      206 patients receiving combined chemotherapy for at least 3 courses for two-year
      overall survival (OS). CA 125 and TPS were applied for monitoring treatment and
      the relationship between marker levels, marker changes and clinical assessments
      was established. Preoperative CA 125 or TPS levels were not correlated with OS in
      FIGO stage I and II patients. After 3 chemotherapy courses the marker levels were
      not correlated with OS in stage I and II. Partial debulking in stage II patients
      was a bad prognostic factor. CA 125 or TPS levels (using a CA 125 discrimination
      level of 25 kU/l and a TPS discrimination level of 100 U/l) after 3 courses of
      chemotherapy were highly significantly correlated with OS in FIGO stages III and
      IV patients: CA 125 two-year OS 67% versus 26% (p < 0.0001) and TPS two-year OS
      55% versus 22% (p < 0.0001). The prognostic value of CA 125 levels after 3
      chemotherapy courses could be further increased by combining CA 125 and TPS
      levels. When both CA 125 and TPS levels were below their respective
      discrimination levels, the two-year overall survival was 75%. When both levels
      were above the discrimination level, the two-year overall survival was only 17%.

PMID- 11326678
TI  - Prognostic relevance of serum vascular endothelial growth factor in ovarian
      cancer.
AB  - BACKGROUND: The vascular endothelial growth factor (VEGF) is the angiogenic
      growth factor most strongly implicated in tumor angiogenesis. Its special role in
      the pathophysiology of ovarian cancer emerges from its dual functional capability
      as an endothelial cell mitogen and a potent stimulator of vascular permeability,
      leading to the characteristic ascites accumulation in this disease. The aim of
      our study was to analyze the prognostic value of serum VEGF (sVEGF) as a tumor
      marker in ovarian cancer. PATIENTS AND METHODS: 41 patients with ovarian
      carcinomas were included in the study. Venous blood was taken from all patients
      preoperatively. From 15 patients an additional postoperative blood sample was
      drawn. sVEGF was measured in duplicate using a commercially available ELISA-kit.
      RESULTS: The mean sVEGF level for the ovarian cancer patients was 522 +/- 321
      pg/ml (SD) (median: 440; range: 55-1263 pg/ml) No statistically significant
      correlation could be found between sVEGF concentration and age, histologic type
      or FIGO-stage. sVEGF values four weeks after surgery were significantly lower
      than those before treatment (p = 0.002). In patients after radical surgery sVEGF
      values dropped or stayed stable below the cut-off more often than in patients
      with residual disease. In the univariate analysis, improved overall survival (OS)
      was found for ovarian cancer patients with a sVEGF below the cut-off value of 440
      pg/ml (p = 0.017). sVEGF was also tested in a multivariate analysis together with
      residual disease and FIGO-stage using the Cox's proportional hazard model. In the
      final model only residual disease had an independent influence on OS (p = 0.018).
      CONCLUSION: sVEGF levels decrease significantly after cytoreductive therapy and
      might indicate treatment efficiency. According to our study, sVEGF is not an
      independent prognosticator of survival for ovarian cancer.

PMID- 11326679
TI  - The impact of squamous cell carcinoma (SCC) antigen in the follow-up after
      radiotherapy in patients with cervical cancer.
AB  - The impact of Squamous cell carcinoma antigen (SCC) in the follow-up of patients
      with cervical cancer treated with radiotherapy was evaluated. 72 patients with a
      histologically proven squamous cell carcinoma of the uterine cervix were treated
      at the Department of Radiotherapy and Radiation Ocology, Munster, Germany. The
      pretherapeutic serum level of SCC was elevated in 60% of patients (cut-off-level:
      2.5 ng/ml). The median serum level correlated with the tumor stage. After the end
      of radiation treatment, 98% of patients in complete remission and 87% of patients
      in partial remission had a serum level below the cut-off. In the case of
      recurrent disease, 71% of patients had a significant increase of SCC serum levels
      before clinical manifestation of relapse. The leading time ranged between one and
      16 months (median: 3.1 months). In conclusion, SCC is a useful tumor marker in
      the follow-up of patients with squamous cell carcinoma of the uterine cervix.

PMID- 11326680
TI  - Serologic angiogenesis factors and microvascular density in renal cell carcinoma:
      two independent parameters.
AB  - Renal Cell Carcinoma (RCC) is characterized by high intratumoral microvascular
      density (iMVD) and significantly elevated serologic titers of angiogenesis
      factors, basic fibroblast growth factor (bFGF), vascular endothelial growth
      factor (vEGF) and angiogenin (Ag). The goal of the present study was to find
      whether a correlation exists between any of these factors and intratumoral
      microvascular density (iMVD). Serologic angiogenesis factors were determined
      directly before nephrectomy of a tumorous kidney in 12 patients (average age:
      67.6 years [49-78] with localized clear-cell RCC (Robson I-II) (Quantikine', R&D
      Systems Europe, Abington, UK). Sections were taken in each case from the
      microscopically most aggressive area of the tumorous kidney preparations.
      Staining was carried out with a primary antibody against CD31 (DAKO M 0823,
      Hamburg, Germany). iMVD was counted at 160x magnification at five "hot spots" 200
      x 200 microns in size, and the individual factors were then correlated with the
      areas of maximum and average iMVD (iMVDmax, iMVD-d). Average concentrations of 38
      pg/ml +/- 68 were found for bFGF, 712 pg/ml +/- 791 for vEGF, and 358 ng/ml +/-
      97 for Ag. iMVDmax was 20 +/- 11 per area, iMVD-d was 410/mm2 +/- 243. No
      correlation was found between microvascular density and serologic angiogenesis
      factors for any parameter. Actual tumor vascularization, expressed as iMVD, was
      not correlated with the 3 angiogenesis parameters which were studied. On the one
      hand, this raises the question whether angiogenesis can be measured at all with
      these parameters; on the other, it remains nuclear whether the continuous process
      of angiogenesis can be registered at all by chronologic, specific factor
      analysis.

PMID- 11326681
TI  - Immunohistochemical investigation with carbohydrate monoclonal antibodies in
      cystic fibrosis.
AB  - BACKGROUND: Cystic fibrosis is one of the most common inherited diseases in
      Europe. In patients with cystic fibrosis, the serum levels of the tumour marker
      antigens CA19-9 and CA50, which are normally found in the epithelium of many
      organs, are increased. No such finding has been reported for CA242, another
      ubiquitous tumour marker antigen. We set out to investigate immunohistochemically
      the correlation of CA19-9 and CA50 with cystic fibrosis and to compare the effect
      of antibodies against these three tumour markers with regard to improved
      immunohistochemical results. MATERIALS AND METHODS: Paraffin-embedded tissue from
      different organs of 18 patients with cystic fibrosis was studied.
      Immunohistochemical reactions were performed with antibodies against CA19-9, CA50
      and CA242 followed by visualisation with the ABC method. RESULTS:
      Immunohistochemical reactions in different tissues were uniform. Anti-CA19-9
      reacted less intensive than anti-CA50 and anti-CA242. The antibodies generally
      bound to cell membranes and compounds of the cytoplasm. CONCLUSIONS: This study
      demonstrates immunohistochemically the epitopes of monoclonal carbohydrate
      antigens (CA-19-9, CA-50 and CA 242) in cystic fibrosis for the first time. We
      also supposed that cystic fibrosis patients show increased serum levels of CA242.
      However, none of the three antibodies investigated seems suitable for the
      immunohistochemical diagnosis of cystic fibrosis.

PMID- 11326682
TI  - Expression of cytokeratins and vimentin in normal human endometrial cells in
      vitro: an immunohistochemical analysis on isolated glandular epithelial cells.

PMID- 11326683
TI  - Expression of the Thomsen-Friedenreich (TF) antigen in the human placenta.
AB  - The Thomsen-Friedenreich (TF) antigen (or, more precisely, epitope; Gal beta 1
      3GalNAc-) has been known for a long time as a pancarcinoma antigen. Here we
      report the immunohistochemical identification of this carbohydrate antigen in the
      human placenta. Paraffin-embedded placental and decidual tissues of the first,
      second and third trimester were incubated with different monoclonal antibodies
      (A78-G/A7 and HH8) directed against the TF-epitope and stained with an
      immunohistochemistry system. We found a strong expression of the TF-epitope in
      the first trimester of pregnancy. In addition, we identified an expression of the
      TF-antigen in the second trimester of pregnancy but only in a few cases a
      positive staining in the third trimester of pregnancy.

PMID- 11326684
TI  - HCG induced hyperthyreosis in germ cell cancer.
AB  - Human germ cell tumors have the unique capacity for totipotential
      differentiation. AFP (the product of normal yolk sac) and HCG (produced by
      trophoblastic tissues) are frequently produced by germ cell tumors. The a-subunit
      of the glycoprotein HCG is identical to that of several pituitary glycoprotein
      hormones (e.g. TSH, LH, FSH), whereas the b-subunit of HCG, TSH, LH and FSH is
      homologous but distinct in the terminal amino acid sequence suggesting that HCG
      is part of a superfamily of gestational hormones. However, the role of TSH within
      this hormone superfamily is still not yet established. A 24-year old patient was
      admitted to our clinic because of a widespread recurrence of a germ cell tumor
      (stage IIIC, Lugano classification). The routine hematologic and blood chemical
      tests were normal, yet, an elevated HCG was found. In addition, increased levels
      of the thyroid hormones FT3 and FT4 were seen, although, this was not associated
      with clinical symptoms of a hyperthyreosis. There was no history of
      hyperthyreosis and thyroidal autoantibody screening revealed normal titers. An
      ultrasound examination of the thyroid gland showed no abnormalities and no iodine
      exposure had occurred during the last months. To mobilize peripheral stem cells
      (PBSC) he was initially treated with paclitaxel (175 mg/m2) and ifosfamide (8.000
      mg/m2)) followed by apheresis of PBSC. The patient was then entered in our phase
      II-study for relapsing germ cell carcinomas using a high-dose chemotherapy regime
      (paclitaxel 175 mg/m2, ifosfamide 9.000 mg/m2, carboplatin 900 mg/m2, etoposide
      900 mg/m2) with subsequent retransfusion of collected stem cells. Due to cranial
      metastases an cranial irradiation was also performed. After three courses of this
      protocol an excellent partial remission of the tumor lesions was achieved and the
      HCG value dramatically decreased. Due to elevated thyroidal hormones, the patient
      was initially treated with thiamazole (20 mg) resulting in decrease of the
      thyroidal hormones. Thus, the thiamazole dose was reduced to 5 mg and then
      omitted. The decrease of the thyroidal hormones FT3 and FT4 strongly correlated
      with the reduction of HCG values (r2 0.91 and 0.77, p < 0.0008). To date there is
      only slight evidence that enhanced HCG levels may cause, at least in part, a
      hyperthyreosis (e.g. gestational hyperthyreosis), however, the underlying
      biochemical mechanism still remains unclear. In this case report we have
      demonstrated a clear positive correlation between HCG levels and thyroidal
      hormones in a patient with germ cell tumor suggesting a direct stimulation of
      hormone producing thyroidal cells by HCG, however, this was not associated with
      clinical symptoms of hyperthyreosis. Currently, several in vitro studies are
      underway in our laboratory to further elucidate the biochemical mechanisms of HCG
      induced hyperthyreosis.

PMID- 11326685
TI  - Is there any correlation between MDR1, GST-pi-expression and CEA?
AB  - BACKGROUND: The levels of mRNA-expression of multidrug resistance (MDR1) and
      glutathione-S-transferase pi (GST-pi) were measured and correlated with the
      immunohistochemical expressions of tumour markers. MATERIALS AND METHODS:
      Analysis of total mRNA was performed by Northern and slot blots. The expression
      of carcinoembryonic antigen (CEA) and other tumour markers was assessed by
      immunohistochemistry. The tumour panel comprised tumours of different
      histologies. RESULTS: CEA-positive tumours showed a significantly higher ex
      pression of MDR1 and GST-pi than CEA-negative tumours. Wilcoxon-Test: mean rank
      of the MDR1 expression (14.3 vs. 7.8; p < 0.05) and GST-pi expression (15.3 vs.
      5.9; p < 0.001). No other correlation could be found. CONCLUSIONS: The
      relationship of MDR1 and GST-pi with the tumour marker CEA implies that
      evaluation of CEA can help in discriminating between tumours with high or low
      expression of drug resistance. Furthermore, correlation between MDR1, GST-pi and
      CEA indicates that there might be a common mechanism, regulating drug resistance
      and expression of CEA.

PMID- 11326686
TI  - PROGINS polymorphism of progesterone receptor is increased in female offspring
      with maternal exposure to diethylstilbestrol.
AB  - DES (Diethylstilbestrol) was used for the treatment of corpus luteum
      insufficiences in early pregnancy. Prenatal exposure to DES leads to an increased
      frequency of vaginal cancer in female offspring. DES causes persistent
      alterations of steroid hormone binding in the vaginal tissue. The frequency of a
      polymorphism (PROGINS) of human progesterone receptor (hPR) gene which is
      associated with an increased risk of sporadic ovarian cancer was tested in DES
      exposed offspring with vaginal dysplasia. Genomic DNA was isolated from the serum
      of 15 US Caucasian DES-offspring. PROGINS analysis was performed using
      sequencing, gel-electrophoresis and SSCP-PCR. The results demonstrated that the
      frequency of PROGINS is increased in DES-offspring (DES: 6.7% homozygous, 26.7%
      heterozygous, normal US Caucasians: 3.3% homozygous, 15% heterozygous). Mutation
      screening of PROGINS is an important advantage for the clinical management of
      screening and can give additional information to prevent or find vaginal cancer
      in early stages in DES-offspring.

PMID- 11326687
TI  - Tumor M2-PK and glutaminolytic enzymes in the metabolic shift of tumor cells.
AB  - The pyruvate kinase isoenzyme M2-PK is known to be associated with a metabolic
      shift that is characteristic for tumor cells. Meanwhile, the universal expression
      of this isoenzyme is the basis for the detection of various tumor diseases in
      human clinical diagnosis. Other enzymes which are known to be essential for this
      tumor specific metabolic shift in rat chemical carcinogenesis are the NADP
      dependent enzymes malic enzyme, isocitrate dehydrogenase and glucose 6-phosphate
      dehydrogenase. To evaluate the role of these enzymes in human carcinogenesis, we
      compared their enzymatic activities in normal colon mucosa and tissues derived
      from primary colon tumors. Histochemical staining showed that the enzyme
      activities were restricted to mucosal colon cells and colon cancer cells. The
      enzymes were strongly but heterogeneously expressed in the tumor tissues, whereas
      staining of normal mucosa was weak. Tumor M2-PK showed the most prominent
      differences in normal colon mucosa and colon cancer cells.

PMID- 11326688
TI  - Human hematopoietic growth factors: old lessons and new perspectives.
AB  - Erythropoietin (EPO), granulocyte colony-stimulating factor (G-CSF) and
      granulocyte-macrophage stimulating factor (GM-CSF) are currently licensed for use
      in cancer patients and play a significant role in the management of anemia and
      neutropenia following myeloblative chemotherapy. EPO was the first recombinant
      hematopoietic growth factor to be used clinically after a number of clinical
      trials which demonstrated its effectiveness in treating mild to moderate cancer
      associated anemia with or without concomitant chemotherapy (particulary
      cisplatin). An extensive research has been made for the improvement of the
      quality of life with EPO therapy, however, when formally assessed, variable
      effects of this important treatment have been observed. Recently, EPO has been
      shown to significantly accelerate hematopoietic reconstitution after peripheral
      blood stem cell transplantation (PBSCT) resulting in reduced infection rates.
      Both, G-CSF and GM-CSF have been shown, in numerous trials, to shorten the period
      of chemotherapy-induced neutropenia, with reduction in attendant morbidity and to
      mobilize PBSC. In addition, administration of both cytokines after PBSCT
      significantly reduced the use of antibiotics and duration of hospitalization
      suggesting an economic benefit. The narrower therapeutic window of GM-CSF at
      higher doses accounts for the fact that it is used much less frequently than G
      CSF. To date, none of the growth factors used clinically has been shown to
      stimulate thrombopoiesis. Although thrombopoietin (TPO) has been found to induce
      megakaryocyte differentiation in vitro, it is unlikely to enter routine clinical
      use for treatment of post-chemotherapy thrombocytopenia, since results of
      clinical trials are not very encouraging, mainly because TPO is difficult to
      schedule and platelet aggregation may occur. Recently, innovative chimeric growth
      factor receptor agonists have been synthesized. Synthokine (SC-55494) (a high
      affinity human IL-3 receptor ligand analog), myelopoietin (MPO) (activates human
      IL-3 and G-CSF receptors) and promegapoietin (PMP) (stimulates the human IL-3 and
      c-mpl receptors) were found to be multilineage hematopoietic growth factors and
      are currently undergoing clinical trials. Preliminary results suggest that these
      compounds may have a major impact on the management of myeloablative chemotherapy
      because of their ability to enhance platelet recovery in addition to their
      neutrophil restorative activity.

PMID- 11326689
TI  - Hormone production in pituitary adenomas following external irradiation: an
      experimental study in rats.
AB  - INTRODUCTION: The aim of this study was to investigate the hormone production in
      pituitary gland tumors following fractionated external irradiation in rats.
      MATERIALS AND METHODS: Sixty female Wistar rats 3 to 4 month of age at the
      beginning of the experiments, were subjected to fractionated roentgen-rays
      exposure, 2 Grays (Gy) daily, either up to 20, 40 or 60 Gy. The animals were
      sacrificed either 6 month or 1 year after completion of the randomly assigned
      irradiation protocol. RESULTS: We found 9 pituitary tumors in 60 irradiated rats
      (15%). All tumors proved to be adenomas. Immunohistochemical analysis of hormone
      production in remnants of the normal adenohypophysis revealed immunoreactivity
      for growth hormone (GH), adrenocorticotropic hormone (ACTH), prolactin (PRL),
      thyroid-stimulating hormone (TSH), and follicle-stimulating hormone (FSH). In
      adenomas, 4 cases were immunoreactive for TSH, 4 for GH, 2 for PRL, and 2 for
      FSH. The tumors were not reactive with anti-ACTH and anti-LH (luteinizing
      hormone). DISCUSSION: We concluded that irradiation accelerates the development
      of pituitary gland adenomas. In our series these tumors were predominantly
      incidental findings at necropsies after pre-termed follow-up, with a variety of
      hormone producing tumor cells. However, 4 of 9 tumors in our study were not
      producing hormones.

PMID- 11326690
TI  - Cytokeratin expression in carcinomas of irradiated rats.
AB  - OBJECTIVE: Laboratory rats can develop benign or malignant tumors (TM)
      spontaneously or following various carcinogenic processes, e.g. irradiation. The
      effects of irradiation vary according to the irradiation field (RF), the dosage
      and the strain of rat. Radiation-induced malignant TM in rats are predominantly
      sarcomas. Carcinomas, especially adenoid-cystic carcinomas (ACC) and
      adenocarcinomas of the head and neck region, are rarely reported in rats. The aim
      of this study was to add to the knowledge on ACC and adenocarcinomas in rats
      developing inside the RF and spontaneously. The TM arose in the course of studies
      on other questions of radiation effects following fractionated irradiation (2
      Gy/day, 5 times a week up to a total dose of 60 Gy). METHODS: We investigated 22
      TM (14 malignant, 8 benign) of 22 female Wistar rats. Ten malignant TM developed
      in the RF and 4 outside of the left head and neck area. The RF comprised the left
      neck, extending from left auricle to left clavicle and included the midline
      organs of the neck. Besides assessment of hematoxylin-eosin (HE)-stained
      sections, epithelial differentiation was investigated using cytokeratin (CK)
      antibodies against CK 5/6, CK 7, CK 8/18, CK 13/15/16, CK 17 and CK 20 and the
      LSAB-2 detection system. RESULTS: Nine malignant TM originated from the major
      salivary glands (SG), a further three from the milk line and two from the
      maxilla. Using HE staining the pattern of rat malignant TM differed from that
      found in humans and was difficult to interpret. Two ACC, two cystadenocarcinomas,
      one microcystic adenocarcinoma and four squamous cell carcinomas (SCC) arising
      from the SG (one SCC was observed in the maxilla) developed in the RF. One
      microcystic adenocarcinoma, one ACC and one adenocarcinoma with sebaceous
      differentiation arising from the milk line and one SCC arising from the maxilla
      were found in non-irradiated animals. As typical results, in the ACC CK 17 was
      distinctly immunoreactive in excretory duct structures (ECD). CK 5/6 and CK
      13/15/16 were marked at variable levels in myoepithelial cells (MC) and in basal
      cells of ECD. In the cystadenocarcinomas the ECD were clearly identified with CK
      17 and CK 8/18 antibodies. MC and basal cells of ECD were positive for CK 5/6 and
      CK 13/15/16 antibodies. CONCLUSION: The CK expression profile of these rare and
      aggressive TM in rats differed according to the entity and SG structure. The
      differentiation markers were predominantly found in ECD and in modified MC.
      Concerning the growth pattern of the TM, the variation in size of the cysts and
      pseudocysts was remarkable. The unusual tumor features reduced the comparability
      with humans. The differentiation pattern did not differ noticeably between TM
      originating inside or outside the RF. Identification of CK subtypes in rat tumors
      facilitates their differential diagnosis.

PMID- 11326691
TI  - Serial CEA and CA 15-3 measurements during follow-up of breast cancer patients.
AB  - OBJECTIVE: CEA and CA 15-3 are adequate parameters for the early diagnosis of
      metastases in breast cancer patients. During the last years serial marker
      measurements have been discussed controversely and moreover accused of
      frightening breast cancer patients in the sense of a tumor marker terror.
      Therefore we evaluated the acceptance and practicability of an intense follow-up
      program including monthly measurements of CEA and CA 15-3. MATERIALS AND METHODS:
      Between 1985 and 1995. 547 breast cancer patients were asked to give blood
      samples every four weeks for CEA and CA 15-3 measurements. In a field research
      study using a half-standardized interview by telephone we evaluated the
      acceptance of serial marker measurements in defined aspects: personal acceptance,
      blood sampling intervals, form of information, role of the home practitioner,
      motivation. RESULTS: 280 patients could be analyzed for the acceptance of this
      follow-up program. 52% of this patient group accepted serial tumor marker
      measurements, while 48% did not. 99% of the participating patients agreed to
      monthly blood sampling intervals compared to only 41% of the non-participating
      patients. 64% of the analyzed patients would have preferred both written and
      personal information about the role of CEA and CA 15-3 and this kind of follow-up
      program. Only in 6% of the participating patients the home practitioner had a
      negative attitude towards monthly tumor marker measurements compared to 36% in
      non-participating patients. Moreover serial marker measurements led to a feeling
      of security and reassurance in 85% of the patients. CONCLUSION: CEA and CA 15-3
      measurements are adequate and accepted instruments for the follow-up and early
      diagnosis of metastases in breast cancer patients. If patients got detailed
      information and support from their home practitioner, serial CEA and CA 15-3
      measurements could lead to a feeling of security in most of the patients.

PMID- 11326692
TI  - New aspects of radionuclide therapy in metastatic bone pain.

PMID- 11326693
TI  - Serum levels of prostate specific antigen in men on hemodialysis.
AB  - The measurement of prostate specific antigen (PSA) is widely used for the early
      detection of prostate cancer. However the influence of renal failure on the serum
      levels of the PSA molecular forms is still a matter of investigation. We
      therefore examined the serum concentration of total and free PSA in patients
      undergoing hemodialysis and discuss the influence of renal failure on both types.
      MATERIALS AND METHODS: Serum concentrations of total PSA, free PSA and the free
      to-total PSA ratio were measured in 48 men undergoing hemodialysis. Total and
      free PSA levels were measured employing a chemiluminescent enzyme immunoassay.
      RESULTS: Serum levels of total PSA, free PSA as well as the free-to-total PSA
      ratio did not change significantly in uremic patients after hemodialysis. Median
      total PSA concentration was 1.1 ng/mL before and 1.15 ng/mL after hemodialysis (p
      = 0.24); median free PSA concentration was 0.29 ng/mL before and 0.32 ng/mL after
      hemodialysis (p = 0.14). Median free-to-total PSA ratio was 0.29 ng/mL before and
      0.31 ng/mL after hemodialysis (p = 0.66). CONCLUSION: Serum free PSA as well as
      total PSA is not eliminated by hemodialysis and the slightly elevated levels of
      free PSA and the free-to-total PSA ratio in uremic patients after hemodialysis
      may be caused by the concomitant decrease in binding proteins. We therefore
      conclude that the reference ranges for total PSA, free PSA and the f-/t-PSA ratio
      are applicable undergoing chronic hemodialysis.

PMID- 11326694
TI  - Multivariate analysis of the prognostic value of CEA and CA 19-9 serum levels in
      colorectal cancer.
AB  - Carcinoembrionic Antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9) are the
      most commonly used tumor-associated antigens in the management of patients with
      colorectal cancer. The aim of this study was to evaluate the prognostic value of
      preoperative serum levels of CEA and/or CA 19-9 and the classical prognostic
      factors (age, sex, tumor infiltration and staging) in 495 patients. PATIENTS AND
      METHODS: The retrospective study was performed on frozen sera (stored at -70
      degrees C) of patients with histologically proven colorectal cancer. Survival
      function estimates were calculated (Kaplan-Meier). The patients were separated
      into two groups according to the preoperative marker levels. Cut-off levels
      calculated at a specificity of 100% versus healthy individuals were used: < 4
      ng/mL versus > or = 4 ng/mL for CEA and < 60 U/mL versus > or = 60 U/mL for CA 19
      9. Survival curve differences were assessed using the log-rank-test. Mulivariate
      Cox's proportional hazard regression analysis was performed to examine the
      association between tumor marker levels and survival time. Classical prognostic
      factors such as age, sex, tumor infiltration, tumor stage (Dukes' classification)
      were included as covariants. The mantel-Haenszel method was used to assess the
      survival rate of patients with colorectal carcinoma and high versus low levels of
      tumor-associated antigens according to tumor stages. RESULTS: The Dukes' stages
      (log-rank chi-square = 231.9; p < 0.0001) represent the best prognostic factor
      besides the preoperative values of CA 19-9 (log-rank chi-square = 162.5). CEA
      shows a log-rank chi-square of 71.4. Thus, CEA and CA 19-9 can be used to
      discriminate two groups of patients with significantly different survival times
      (p < 0.0001). The importance of different parameters in providing additional
      prognostic information was evaluated by multivariate analysis. Only items of
      statistically significant prognostic relevance (univariate analysis) were used
      for this analysis. Estimated relative risks of death adjusted for tumor stage
      were 5.5 considering Dukes' stage A versus Dukes' stage B/C and Dukes' stage B/C
      versus Dukes' stage D, respectively, and an increasing relative risk of 27.5 for
      Dukes' stage A versus Dukes' stage D (p < 0.001). The relative risk for
      preoperative CA 19-9 serum concentrations (> or = 60 U/mL versus < 60 U/mL) was
      2.3 (p < 0.001) and for preoperative CEA concentrations (> or = 4 ng/mL versus <
      4 ng/mL) 1.4 (p < 0.07). For CEA the 2-year survival rates in the group of
      patients with preoperative serum concentrations > 4 ng/mL versus < 4 ng/mL and
      Dukes' stage D were 16% versus 38%, in Dukes' stage B/C 73% versus 91% and in
      Dukes' stage A 100% versus 98%. For CA 19-9 the 2-year survival rates in the
      group of patients with preoperative serum concentrations > or = 60 U/mL versus <
      60 U/mL and Dukes' stage D were 10% versus 39%, whilst in Dukes' stage B/C 58%
      versus 87%. In the group of patients with Dukes' stage A with serum levels > or =
      60 U/mL a 2-years survival rate of 100% was found. CONCLUSION: The postoperative
      Dukes' classification represents the best prognostic information besides the
      preoperative values of CA 19-9. The predictive information provided by
      preoperative CA 19-9 serum levels is independent from that obtained by the other
      factors investigated. Only Dukes' classification and CA 19-9 levels showed
      statistical significance (p < 0.001).

PMID- 11326695
TI  - Improvement of survival by efficacy orientated sequential polychemotherapy of
      exocrine pancreatic cancer.
AB  - Results of palliative chemotherapy in 104 patients suffering from exocrine
      pancreatic carcinomas are presented. First-line therapy included intraarterial
      approaches with gemcitabine + mitomycin-C and intravenous systemic treatments
      with gemcitabine, gemcitabine + mitomycin-C and oxaliplatin, respectively. In
      addition, it was the aim to improve survival by adding second- and third-line
      chemotherapies, mainly including high dose 5-FU/FA and irinotecan resp. alone or
      in combinations. Follow-up included clinical investigations, imaging methods and
      determination of tumor markers. Evaluation of efficacy followed the WHO
      guidelines. The results indicated the intraarterial locoregional treatment of
      exocrine pancreatic cancer with a combination of mitomycin-C + gemcitabine as a
      highly effective treatment modality with PR + CR of 40% measured by imaging
      methods and 81% analysed by tumor marker determinations. The survival analyses
      suggested relevant prolongation of survival in relation to the number of
      effective second- and/or third-line therapies (0/1/> 1) with median survival-
      based on the imaging data--of 7, 11 and 20 months for Mo tumors and 3, 8 and 14
      months for tumor diseases with liver metastases at time of admission,
      respectively. Relevant preconditions for second- and/or third-line therapies of
      pancreatic carcinomas are given by more or less effective first-line treatment
      modalities of this cancer disease on the one hand and by the actual diagnostic
      aids allowing the beginning of first-line therapy as well as the detection of
      recurrence early enough to try a second- or third-line therapy before
      clinical/ethical aspects prevent further antitumoral treatment trials in the
      individual patient.

PMID- 11326696
TI  - Irinotecan(Campto R): efficacy as third/forth line therapy in advanced pancreatic
      cancer.
AB  - Following the concept that the actual survival of pancreatic cancer patients can
      only be significantly improved by sequential poly-chemotherapy (EOSPC) in order
      to add one or two further progression free-survival times (PFST), in addition to
      the potential antitumoral effects of a first- or second-line therapy we studied
      the therapeutic efficacy of a third- or fourth-line chemotherapy with irinotecan
      alone, or in combination with oxaliplatin and high dose 5-FU/FA respectively, in
      a pilot study in 17 patients. Follow-up was performed on the basis of clinical
      investigations, imaging methods and the course of tumor markers, mainly CT and CA
      19-9. The overall response rate in these cases of third/fourth-line therapies was
      1 PR, 4 MR, 6 SD in the imaging methods compared to 5 PR, 2 MR and 5 SD on the
      basis of the tumor marker courses in the serum. The median PFST amounted to 4
      months. Side effects could be seen as reported in the literature. Only in 1
      patient did treatment have to be stopped due to irinotecan-induced
      gastrointestinal symptoms. Our data might suggest that combinations are more
      effective than irinotecan alone. However, further studies have to demonstrate
      whether irinotecan alone or in combination with e.g. oxaliplatin and 5-FU/FA will
      be more effective. The results suggested that irinotecan alone or in combination
      might also be used as third- and fourth-line therapeutical trials in exocrine
      pancreatic cancer in order to improve the survival time of these patients based
      on efficacy orientated sequential poly-chemotherapy (EOSPC).

PMID- 11326697
TI  - External quality control program for inter-laboratory quality control.
AB  - BACKGROUND: The accuracy and precision of tumor marker testing is of high
      clinical importance requiring the implementation of effective quality control
      procedures in the diagnostic laboratory. An external quality control program
      including an inter-laboratory comparison could be of help in improving the
      quality of test results. MATERIALS AND METHODS: Laboratories using BIOREF
      reference material sent their routine internal quality control results of each
      monthly control period to the evaluation center for statistical analysis and
      inter-laboratory comparison. RESULTS: The inter-laboratory comparison showed that
      the mean values of test results obtained by different laboratories can vary
      considerably especially when different test kits are used. A comparison of test
      results of laboratories using the same test kit showed much better correlation
      but discrepancies of coefficients of variation between these laboratories were
      still observed. CONCLUSION: An external quality control program revealed problems
      in the accuracy and precision of tumor marker test results in the individual
      laboratory, which could serve as a basis for the improvement of test performance.

PMID- 11326698
TI  - The expression of angiopoietins and their receptor Tie-2 in human prostate
      carcinoma.
AB  - BACKGROUND: Angiopoietin-1 and angiopoietin-2 are antagonist angiogenic factors
      acting via the same receptor Tie-2. Their role in prostate carcinoma (PCa) is not
      known. MATERIAL AND METHODS: Using immunohistochemistry, localization of
      angiopoietin-1, angiopoietin-2 and their receptor Tie-2 was studied in normal
      human prostate and PCa. RESULTS: Few epithelial cells of normal prostate
      expressed angiopoietin-1 and Tie-2 but not angiopoietin-2. Normal prostate blood
      vessels were negative. In PCa, intraductal grown tumor cells showed angiopoietin
      1 but not angiopoietin-2. Blood vessels close to the ducts and some apical tumor
      cells expressed angiopoietin-1 and Tie-2. In glandular PCa, most of the tumor and
      intraglandular stromal cells were positive for both angiopoietin-1 and
      angiopoietin-2. Angiopoietin-1 and angiopoietin-2 were also found in tumor
      capillaries. Additionally, angiopoietin-2 was expressed in smooth muscle cells of
      intratumoral blood vessels which also exhibited Tie-2. CONCLUSIONS: The results
      presented indicate a role of angiopoietin-Tie-2 system, particularly of
      angiopoietin-2 in the vascularization of PCa.

PMID- 11326699
TI  - Dose-response relationships and the effect of age and latency period on the
      expression profile of laminin in irradiated rat mandibular glands.
AB  - OBJECTIVE: The extent of radiogenic salivary tissue damage (direct cell damage,
      reactive cell infiltration, increasing fibrosis) depends on the radiation dose
      (RD), the fractionation (FN) and the localisation of the salivary gland (SG) in
      the radiation field (RF). Because the histological damage is characterized by
      cellular and structural alterations and because extracellular matrix proteins,
      for example laminin (LA), are among the main components of the basement membrane
      (BM), which is considered to possess cell- and tissue structure-regulating
      functions, we set out to describe radiogenic BM changes. MATERIALS AND METHODS:
      In 124 rat mandibular SG we investigated HE-stained sections and the LA staining
      profile (LASP) dependent on age [1 year (y) vs. 1 1/2 y], on FN [2 Gy/day up to a
      total dosage of 20/40/60 Gy (X-rays)], on RF [(left head and neck area); inside
      (left-sided SG) vs. outside (right-sided SG) RF] and on the latency of
      irradiation (1/2 y vs. 1 y) using immunohistochemical methods and multivariate
      analysis. RESULTS: The immunoreactivity of the polyclonal antibody in the rat did
      not differ from the LASP in humans. LA was detected at variable levels in the
      glandular tissue, in vascular walls (without staining in the adventitia) and in
      nerve tissue (NT). No reaction was found in the capsule and the trabecula. In
      irradiated SG most tissue structures, including the vascular wall and NT, showed
      significantly stronger staining (both increased intensity and more extended
      expression). With increasing RD from 20 Gy to 60 Gy we found an increasing
      staining reaction. In addition, conglomerated LA depots were noted, especially in
      ares of disturbed or former acini of glands exposed to 60 Gy. The LASP up to 20
      Gy was non-uniform and did not differ significantly from that in controls. A
      remarkable finding was the similar dose-dependent increase in staining reaction
      on both sides in several tissues of irradiated animals. Predominantly, however,
      we found considerably greater increases in staining in directly exposed glands
      than in out-of-field glands. Age and time since irradiation had no significant
      effect on staining. CONCLUSION: The BM constituent LA showed dose-dependent
      increases in expression--analogous to positively dose-dependent increasing SG
      tissue damage--which could contribute to disturbed cell-matrix interaction and SG
      radiation damage. Several parenchymal structures may be more sensitive to
      possible scattered radiation.

PMID- 11326700
TI  - Technical performance of the Elecsys CA 72-4 test--development and field study.
AB  - Tumor-associated glycoprotein (TAG) 72 is a mucin-like protein of high molecular
      weight (220-400 kd). Elevated serum levels of TAG72 are preferentially observed
      in patients suffering from gastric cancer. Additionally the determination of
      TAG72 may be a helpful tool in the management of patients suffering from mucinous
      ovarian cancer, in whom the clinical sensitivity of CA125 is low. The new Elecsys
      CA72-4 assay-available as Elecsys 2010 and 1010--was evaluated in a first field
      study. The test has a wide measuring range (300 U/ml) and low detection limit
      (0.5 U/ml) which favours its routine use. Typical precision values are 2% for
      intra-assay, 4% for inter-assay and 6% for inter-instrument-precision. Method
      comparisons to Enzymun-Test CA72-4 showed a correlation between 0.91 and 0.96.
      The correlation to a commercially available RIA was 0.8. With human ascites
      material no Hook-effect was observed up to 20,000 U/ml. No Hama-interference with
      clinically relevant HAMA-samples was detected.

PMID- 11326701
TI  - Dde I RFLP may falsify linkage analysis of hereditary retinoblastoma when using
      SSCP of p88PR0.6 region.
AB  - The polymorphic p88PR0.6 locus (Xba I RFLP) in intron 17 of the retinoblastoma
      gene is a DNA marker with high informative content frequently used for linkage
      analysis of familial retinoblastoma. We identified an unreported Dde I
      restriction fragment length polymorphism close to the polymorphic Xba I
      recognition site that interferes with the SSCP analysis of the PR0.6 region. We
      have named this new polymorphism RB1.17. Under most electrophoresis conditions,
      the single strand conformations reflect the Dde I genotype rather than that of
      Xba I. The chromosomal localization, allele frequencies, inheritance and PCR
      based detection of the Dde I RFLP which is useful for linkage analysis itself are
      reported.

PMID- 11326702
TI  - The significance of CEA, CA19-9 and CA72-4 in the detection of colorectal
      carcinoma recurrence.
AB  - The significance of CEA, CA19-9 and CA72-4 was evaluated the for early detection
      of disease recurrence, on the basis of retrospective evaluation of routine data
      in patients with colorectal carcinoma. They also considered the dependence of the
      results of these data analyses on the definition of groups of patients, both with
      no evidence of disease (NED) and with recurrence of disease (RD). PATIENTS AND
      METHODS: From January 1994 to March 1999 serum levels of CEA, CA19-9 and CA72-4
      were determined in the follow-up of 517 patients with colorectal cancer and
      compared with the retrospectively confirmed clinical status of the patients.
      RESULTS: CEA and CA19-9 showed comparable sensitivities in the detection of
      locoregional recurrence of colorectal carcinoma, whilst the sensitivity of CA72-4
      was considerably lower. CEA is an optimal marker for detecting distant
      metastases, in particular liver metastases, since its sensitivity considerably
      exceeds the sensitivities of the other two monitored markers. CONCLUSION: Using
      routine data required detailed analysis and clear definitions of groups of
      patients with NED and RD. The following conclusions for the evaluation of data
      were drawn from this analysis: a) Tumor marker cut-off values and sensitivities
      related to 95% specificity of remission values depended strongly on the given
      definition of the groups of patients with NED and RD. b) The patient group with
      NED is best characterized as the group of patients who never developed
      progression and where all the values which were assessed within a period shorter
      than six months from the end of therapy and follow-up, or less than six months
      before progression, death, or before the last marker assessment in the patient,
      were excluded. c) For the optimal characterisation of the group of patients with
      RD it is recommended only to consider values obtained during the first
      progression, after the period of complete post-operative or post-therapeutic
      remission. d) These conclusions refer not only to routine data, where this
      correction represents a condition for reliable evaluation, but also to any
      research done, since they ensure complete homogeneity of the group and mutual
      comparability of the results.

PMID- 11326703
TI  - Comparison of the test methods (KRYPTOR, ES 600 and CIS-RIA) for CEA, CA 15-3 and
      CA 125 follow-up and ONCOCHECK-quality control.
AB  - We examined whether the automated KRYPTOR/CIS analysis system could replace the
      routine tumor marker tests. We analysed the sera of 50 patients by
      EnzymImmunoAssay CEA (ES-600, Roche/Boehringer), CA 15-3 (ELSA/RIA; CIS) CA 125
      (Centocor/RIA; CIS) and in parallel by KRYPTOR (CIS). The correlation coefficient
      for CEA and CA 125 was clearly less than that of Centocor. Although the automated
      KRYPTOR is suitable for routine analysis a larger number of patients sera must be
      tested by different methods, especially in view of the lack of international
      reference material, before completely switching over to KRYPTOR.

PMID- 11326704
TI  - Human anti-mouse antibodies: pitfalls in tumor marker measurement and strategies
      for enhanced assay robustness; including results with Elecsys CEA.
AB  - Therapies using monoclonal antibodies may have undesirable consequences for the
      diagnostic use of tumor markers. These effects can be minimised by employing
      chimeric antibodies as well as special interference eliminating reagents. Human
      Anti-Mouse Antibodies (HAMA) are produced as a result of the immune response of a
      patient to treatment with murine monoclonal antibodies. The interaction of HAMA
      with the murine monoclonal antibodies of a tumor marker assay can simulate
      (false) positive or negative results leading to misdiagnosis and to inadequate
      disease management of a patient. To avoid HAMA-interferences "Roche Diagnostics"
      established a three-component-system: The use of chimeric antibodies, the
      interference elimination, which is realised in the parameters most frequently
      used like CEA and TSH. By employing such a chimeric antibody, Elecsys CEA proved
      to be extremely robust against HAMA-interferences. With 20 clinical relevant
      samples from different Mab-approaches, no HAMA-interference was observed. By
      fragmentation of the antibodies, i.e., elimination of the constant region and
      using monovalent fab-fragments (antigen binding fragment) combined with the
      addition of special blocking reagents all not-chimerized, Elecsys assays showed
      comparable results to chimerisation. This could also be shown with 20 clinical
      relevant samples.

PMID- 11326705
TI  - Analysis of molecular isoforms of PSA and their ratios in men with PSA-relapse
      after radical prostatectomy.
AB  - BACKGROUND: The aim of this study was the longitudinal comparison of % f-PSA in
      patients before radical prostatectomy and after PSA relapse. Is % f-PSA a
      consistent tumor specific parameter or does this ratio change during untreated
      tumor progression? MATERIALS AND METHODS: In this study 41 out of 420 patients
      with untreated increasing PSA-progression (> 0.5 ng/ml) were analysed. Patients
      with neoadjuvant or adjuvant hormonal therapy were excluded. T-PSA were f-PSA
      were analyzed by Immulite DPC (Diagnostic Products Coop., CA) and Abbott Axsym
      (Abbott Park, Il, USA). RESULTS: Pre-operative % f-PSA ratio was 10.6% (range 4.6
      22%; Std. dev.: 4.9); T-PSA concentration was 26.4 ng/ml (range 5.5-10.2 ng/ml
      Std. dev.: 20.3). In men with PSA relapse after radical prostatectomy % f-PSA
      ratio was 14.73% (range 2.2-4.5% Std. dev.: 9.7). Repeated post-operative % f-PSA
      measurements resulted in 12.94% f-PSA (range 2.7-3.8% Std. dev.: 9.9%) with a
      regression of R = 0.57. All men with pre-operative elevated % f-PSA (> 15%) had
      post-operative elevated % f-PSA. CONCLUSIONS: The data indicates that post
      operative % f-PSA is a constant tumor specific parameter in men with untreated
      PSA relapse after radical prostatectomy. Post-operative % f-PSA was higher
      compared with pre-operative % f-PSA concentrations. No correlation with Gleason
      score or pathological stage was found.

PMID- 11326706
TI  - Chromogranin A: an additional tumor marker for postoperative recurrence and
      metastases of medullary thyroid carcinomas?
AB  - In this study, plasma concentrations of chromogranin A, calcitonin and
      carcinoembryonic antigen (CEA) were measured in 40 healthy volunteers as well as
      in 129 patients with recurrences and/or metastases of neuroendocrine tumors and
      of medullary thyroid carcinomas (MTCs). A double antibody assay was employed
      using polyclonal rabbit antibodies to a C-terminal fragment of the protein for
      detection of human chromogranin A. Using ROC analysis, a cutoff at 22 U/l
      chromogranin A was calculated. In patients with neuroendocrine tumours, much
      higher serum concentrations of chromogranin A than for patients with MTC (80% vs.
      46%) were measured. The following sensitivities were found: chromogranin A; 46%,
      calcitonin 100%, CEA 52%. Furthermore, the mean values of chromogranin A
      concentrations correlated with the tumour mass and/or number of metastases in MTC
      and neuroendocrine tumours. Evaluation of follow-up studies remains to be
      completed; however, preliminary results showed similarities regarding the
      behaviour of chromogranin A and calcitonin. Despite the findings of this study,
      the observations could not confirm chromogranin A as a reliable marker for
      metastazing or recurrent MTC.

PMID- 11326707
TI  - The tobacco-using client: clinical issues.
AB  - Dental hygienists must be aware of the clinical ramifications of tobacco use. By
      pointing out tobacco-induced periodontal alterations to clients, a teachable
      moment begins. When clients see deleterious changes occurring in their own oral
      cavities, their habits become personalized. Then they can begin to claim
      ownership of their habit and consider other alternatives. Caring, empathetic, and
      non-judgmental communication can help steer the client to the path of cessation.
      For clients not ready to abstain, the dental hygienist's appropriate clinical
      interventions and educational messages will help preserve the periodontium to the
      best extent possible. It is critical that clients realize that continued tobacco
      use will only exacerbate a preexisting periodontal condition. Thus, the tobacco
      using client presents challenging educational and clinical opportunities for the
      dental hygienist.

PMID- 11326708
TI  - Quitlines: telephone support for quitting smoking.

PMID- 11326709
TI  - Smokeless tobacco and oral cancer.

PMID- 11326710
TI  - Pharmacological aids for smoking cessation.
AB  - To smokers, nicotine addiction is a powerful vice that is difficult to overcome
      even with pharmaceutical aids. Relapse rates are high and maintaining a
      successful quitting strategy is difficult regardless of the method used.
      Therefore, clinicians should routinely provide positive feedback to help maintain
      their patients' cessation. Encouraging smoking cessation, selecting appropriate
      products, and monitoring and supporting patients through their withdrawal
      symptoms makes for a more complete therapeutic care plan for cessation of tobacco
      use. In the long term, helping patients to succeed in their cessation treatment
      has the potential to reduce healthcare costs, save clinicians time and money, and
      improve morbidity and mortality rates.

PMID- 11326711
TI  - A clinico-pathologic correlation. Erythema multiforme.

PMID- 11326712
TI  - Smoking cessation can begin in the dental office.

PMID- 11326713
TI  - Smoking-associated oral pathoses.

PMID- 11326714
TI  - The management of chronic obstructive pulmonary disease (COPD).

PMID- 11326715
TI  - Medical management of spasticity in stroke.

PMID- 11326716
TI  - Falls prevention.

PMID- 11326717
TI  - Making decisions: implications for practice of the Government's proposals for
      making decisions on behalf of mentally incapacitated adults in England and Wales.

PMID- 11326718
TI  - Prosthodontic management of periodontally compromised patient.
AB  - The fabrication and placement of a conventional immediate denture following
      extraction of periodontally compromised, non-restorable remaining teeth is a
      method that is frequently used to help restore form and function in an
      esthetically pleasing manner. This technique demands knowledge in applied basic
      sciences and prosthodontic principles. Accurate diagnosis and scrupulous
      treatment planning help the dentist address the patient's needs.

PMID- 11326719
TI  - Parotid gland swelling in HIV diffuse infiltrative CD8 lymphocytosis syndrome.
AB  - The signs and symptoms of diffuse infiltrative CD8 lymphocytosis syndrome (DILS),
      a subset of HIV, include parotid swelling, cervical lymphadenopathy and a
      serologic CD8 elevation. A case report is used to illustrate the condition.
      Patients with the syndrome will be seen in the dental office. Recognition and
      appropriate referral are responsibilities of the dental practitioner.

PMID- 11326720
TI  - Prevention of cancers of oral cavity and pharynx in New York State.
AB  - Cancers of the oral cavity and pharynx affect a significant number of people in
      New York State. The disease incidence has not changed in the past three decades.
      Despite dramatic improvements in surgical and reconstructive techniques in that
      time, the overall mortality rates for oral and pharyngeal cancer remain
      relatively unchanged. The overall five-year survival rate for persons with oral
      and pharyngeal cancer is only 52%. Although the risk factors are known and
      lesions in the oral cavity and pharynx are easily accessible for early detection,
      the lack of progress in controlling this cancer is perplexing. The lack of
      awareness of the disease burden and the risk factors, the tendency for occurrence
      in lower socioeconomic and poorly compliant populations, and the lack of a simple
      screening test have hindered progress.

PMID- 11326721
TI  - Do as I say, not as I tried to do.

PMID- 11326722
TI  - Medicaid program demands scrupulous attention to details.

PMID- 11326723
TI  - Workers' perceptions of how jobs affect health: a social ecological perspective.
AB  - A national sample of 2,048 workers was asked to rate the impact of their job on
      their physical and mental health. Ordered logistic regression analyses based on
      social ecology theory showed that the workers' responses were significantly
      correlated with objective and subjective features of their jobs, in addition to
      personality characteristics. Workers who had higher levels of perceived
      constraints and neuroticism, worked nights or overtime, or reported serious
      ongoing stress at work or higher job pressure reported more negative effects.
      Respondents who had a higher level of extraversion, were self-employed, or worked
      part time or reported greater decision latitude or use of skills on the job
      reported more positive effects. These findings suggest that malleable features of
      the work environment are associated with perceived effects of work on health,
      even after controlling for personality traits and other sources of reporting
      bias.

PMID- 11326724
TI  - Organizational adoption of preemployment drug testing.
AB  - This study explored the adoption of preemployment drug testing by 360
      organizations. Survival models were developed that included internal
      organizational and labor market factors hypothesized to affect the likelihood of
      adoption of drug testing. Also considered was another set of variables that
      included social and political variables based on institutional theory. An event
      history analysis using Cox regressions indicated that both internal
      organizational and environmental variables predicted adoption of drug testing.
      Results indicate that the higher the proportion of drug testers in the worksite's
      industry, the more likely it would be to adopt drug testing. Also, the extent to
      which an organization uses an internal labor market, voluntary turnover rate, and
      the extent to which management perceives drugs to be a problem were related to
      likelihood of adoption of drug testing.

PMID- 11326725
TI  - Unintended consequences: organizational practices and their impact on workplace
      safety and productivity.
AB  - Managers often implement new organizational practices to improve firm performance
      while neglecting possible side effects. This study examines the relationship
      between 6 organizational practices and both productivity and injury rates in 86
      small manufacturing firms. The use of performance-based pay was associated with
      higher injury rates and lower productivity (on 1 of 2 measures). The opposite
      pattern held for training: Training hours were negatively related to the injury
      rate and positively related to 1 measure of productivity. Surprisingly, higher
      hours worked per week was associated with a lower injury rate and also with lower
      productivity. The use of teams was associated with a lower injury rate but was
      unrelated to productivity. The potential interaction between hazard control
      measures and organizational practices in predicting injury rates is also
      discussed.

PMID- 11326726
TI  - The effects of job insecurity on employee safety outcomes: cross-sectional and
      longitudinal explorations.
AB  - Job insecurity research has focused primarily on attitudinal (e.g., job
      satisfaction), behavioral (e.g., employee turnover), and health outcomes.
      Moreover, research in the area of workplace safety has largely focused on
      ergonomic factors and personnel selection and training as primary antecedents of
      safety. Two cross-sectional structural equational modeling analyses and 1
      longitudinal regression analysis of 237 food-processing plant employees unite
      these 2 disparate areas of research by exploring the relatively uncharted
      relationship between job insecurity and safety outcomes. Results indicate that
      employees who report high perceptions of job insecurity exhibit decreased safety
      motivation and compliance, which in turn are related to higher levels of
      workplace injuries and accidents.

PMID- 11326727
TI  - The relationship between response rate and effect size in occupational health
      psychology research.
AB  - This study investigated the relationship between response rate and effect size in
      self-report survey research. The correlation between response rate and effect
      size was calculated for 4 variable combinations, and the results were combined
      using meta-analytic procedures. The correlation of response rate and effect size
      was not significant for any individual sample. The average correlation between
      response rate and effect size was -.15, with a nonsignificant corrected variance
      across studies of .02. These results suggest only a small relationship between
      the response rate of a survey and the reported effect size between variables.

PMID- 11326728
TI  - Career involvement and family involvement as moderators of relationships between
      work-family conflict and withdrawal from a profession.
AB  - This study extended prior analyses by J. H. Greenhaus, K. M. Collins, R. Singh,
      and S. Parasuraman (1997) by examining relationships between 2 directions of work
      family conflict (work-to-family conflict and family-to-work conflict) and
      withdrawal from public accounting. The sample consisted of 199 members of the
      American Institute of Certified Public Accountants (135 men and 64 women) who
      were married or in a long-term relationship and who had 1 or more children. It
      was found that work-to-family conflict (but not family-to-work conflict) was
      positively related to withdrawal intentions. In addition, relationships of work
      to-family conflict with withdrawal intentions and withdrawal behavior were
      stronger for individuals who were relatively uninvolved in their careers than for
      those who were highly involved in their careers. The implications of the findings
      for future research are discussed.

PMID- 11326729
TI  - [Medical economics in year 2001 as exemplified by Helicobacter pylori].

PMID- 11326730
TI  - [Practice guidelines in medicine--validity for clinical application?].

PMID- 11326731
TI  - [Chromoendoscopy, magnification endoscopy, optic biopsy; showmanship or actual
      improvement?].

PMID- 11326732
TI  - [New endoscopic therapeutic procedures].

PMID- 11326733
TI  - [Diagnosis of diseases of the biliary-pancreatic system and intestines: options
      and limitations of magnetic resonance tomography].

PMID- 11326734
TI  - [Chronic hepatitis--new therapeutic options].

PMID- 11326735
TI  - [Irritable bowel syndrome--role of motility inhibitors].

PMID- 11326736
TI  - [Chronic inflammatory bowel diseases: drug therapy standards and trends].

PMID- 11326737
TI  - [Acute liver failure].

PMID- 11326738
TI  - [Refractory angina pectoris in end-stage coronary disease; relief through
      neuromodulation?].

PMID- 11326739
TI  - [20-year old patient with bilateral flank pain, visual loss, redness, pain and
      photophobia in both eyes].

PMID- 11326740
TI  - [Parenteral iron replacement: indications and risks].

PMID- 11326741
TI  - [Glitazones. Profile of a new class of substances].

PMID- 11326743
TI  - Ligand-receptor-mediated drug delivery: an emerging paradigm in cellular drug
      targeting.
AB  - Receptor-mediated cellular events have received major attention in the field of
      drug/gene delivery in the past few years. These events, which are mediated
      through the endogenous ligands/epitopes, could be exploited for designing site
      specific and target-oriented delivery systems. The past decade has seen the
      development of endogenous ligands and their mimics of exogenous origins to
      selectively deliver the contained or immobilized moieties to the cellular
      interiors using a wide range of cell surface receptors/epitopes. Ligand-mediated
      active targeting has emerged as a novel paradigm in targeting either vascular
      compartment (first-order), cellular (second-order), or intracellular (third
      order) levels. Most carrier systems or bioconjugates explored so far can be used
      as cargo units for the site-specific presentation and delivery of various
      bioactives using biorelevant ligands, including antibodies, polypeptides,
      oligosaccharides (carbohydrates), viral proteins, fusogenic residues, and
      molecules of endogenous origin. In this review, we describe various ligand
      receptor systems that have been investigated to date for targeted or cellular
      drug delivery. These include blood carbohydrate (lectin) receptors, Fc receptors,
      complement receptors, interleukin receptors, lipoprotein receptors, transferin
      receptors, scavenger receptors, receptors/epitopes expressed on tumor cells, and
      cell adhesion receptors. The role of receptors as molecular target has opened new
      opportunities for cellular or intracellular targeting using carrier systems
      appended with targeting handles (ligands). Research in the field of ligand
      receptor-based targeted system is expected to be an armamentarium and the focal
      point of research in the next millennium.

PMID- 11326744
TI  - Improved drug delivery using microemulsions: rationale, recent progress, and new
      horizons.
AB  - Microemulsions are excellent candidates as potential drug delivery systems
      because of their improved drug solubilization, long shelf life, and ease of
      preparation and administration. The formulation of microemulsions for
      pharmaceutical use requires a thorough understanding of the properties, uses, and
      limitations of microemulsions. Three distinct microemulsions--oil external, water
      external, and middle phase--can be used for drug delivery, depending upon the
      type of drug and the site of action. In this article, we present an examination
      of microemulsions as drug carrier systems, starting with general information and
      moving to a thorough review of the microemulsion literature, with a special
      section devoted to microemulsion-based gels.

PMID- 11326745
TI  - Localization of human airway trypsin-like protease in the airway: an
      immunohistochemical study.
AB  - Human airway trypsin-like protease (HAT) has been isolated from mucoid sputum of
      patients with chronic airway diseases. In order to clarify the cellular source of
      this novel protease in the human airway, we examined the localization of
      immunoreactive HAT in bronchial tissues obtained at surgery and fixed in 4%
      paraformaldehyde using an extremely sensitive immunohistochemical technique
      called a catalyzed signal amplification method and a monoclonal antibody against
      recombinant HAT. HAT immunoreactivity was demonstrated in cytoplasm of ciliated
      cells of bronchial epithelium and/or at the basal part of cilia. No positive
      reaction was found in submucosal glands or mast cells. The heterogeneous
      distribution of HAT immunoreactivity within the bronchial epithelium indicates
      that its expression might be changeable and that it might be closely related to
      the physiological status of the airway epithelium. Non-specific but intense
      reaction caused by endogenous avidin-binding activity (EABA) was selectively
      detected in submucosal glands, but was effectively blocked by successive
      treatments with avidin and biotin. These results indicate that HAT may be
      synthesized in the ciliated cells and that it may play some physiological roles
      within the epithelial layer and on the airway surface. It is necessary to keep in
      mind that some cells show strong EABA, especially when a highly sensitive
      immunohistochemical technique is applied.

PMID- 11326746
TI  - Localization of mouse CLC-6 and CLC-7 mRNA and their functional complementation
      of yeast CLC gene mutant.
AB  - CLC-6 and CLC-7 belong to the family of voltage-dependent chloride channels. To
      learn more about the in vivo roles of CLC-6 and CLC-7, we performed in situ
      hybridization of these CLC channels in various mouse organs. Mouse CLC-6 (mCLC-6)
      was expressed in the peripheral region of seminiferous tubules in the testis,
      tracheal epithelium, epithelium of bronchioles, alveolar cells in the lung,
      acinar cells in the pancreas, and intestinal epithelium, but we could not detect
      signals from pancreatic islets. Mouse CLC-7 (mCLC-7) was expressed in neurons in
      the medulla oblongata, Purkinje cells in the cerebellum, proximal tubules in the
      kidney, and hepatocytes in the liver. The distribution of mCLC-6 and mCLC-7 were
      similar in the lung, pancreas, and testis. mCLC-6 functionally complemented the
      gef1 phenotype of a yeast strain in which a single CLC channel (GEF1) had been
      disrupted by homologous recombination. In contrast, mCLC-7 did not complement
      this gef1 phenotype. This study identified the cell types that express mCLC-6 and
      mCLC-7 in the mouse tissues, and the complementation assay suggested that mCLC-6
      functions as an intracellular chloride channel.

PMID- 11326747
TI  - Immunolocalization of iron regulatory protein expression in the murine central
      nervous system.
AB  - We examined the expression of the iron regulatory proteins 1 and 2 (IRP1 and
      IRP2) in the brains of adult (4-6 months) CBA/J mice. Anti-IRP1 immunoreactivity
      was localized to cell bodies, including putative neurons and oligodendrocytes. In
      contrast, anti-IRP2 staining was prevalent throughout the neuropil of regions of
      the brain consistent with the central autonomic network (CAN) and mossy fibers
      emanating from hippocampal dentate granule cells. Essentially no staining for
      IRP2 was observed in the cerebellum in contrast to strong IRP1 immunoreactivity
      in Purkinje cells. Notably, cells within one vestibular nucleus exhibited
      staining by both IRP1 and IRP2. Our results suggest distinct roles for IRP1 and
      IRP2 in the regulation of iron homeostasis in the mammalian nervous system where
      IRP1 may provide a maintenance function in contrast to IRP2 that could
      participate in modulating proper CAN functions, including cardiopulmonary,
      gustatory as well as fine motor control.

PMID- 11326748
TI  - Most apoptotic cells in mdx diaphragm muscle contain accumulated lipofuscin.
AB  - An age-related pigment, lipofuscin (LF), which accumulates in postmitotic, long
      lived cells, is formed by the oxidative degradation of cellular macromolecules by
      oxygen-derived free radicals. In the present study we show that LF is accumulated
      in some myofibres, myosatellite cells and interstitial cells in the diaphragm
      muscles of the X chromosome-linked muscular dystrophic (mdx) mice at the age of
      10 weeks when repetitive cycles of de- and regeneration of myofibres occur. In
      contrast, LF is virtually absent in diaphragm muscles of age-matched C57BL/10
      (C57) normal control mice. Therefore, mdx muscle is more susceptible to oxidative
      stress than normal muscle. We hypothesise that gene-regulated cell death
      (apoptosis) occurs in dystrophic muscle cells that accumulate LF as a consequence
      of either oxidative stress or injury. We found that 74-79% of apoptotic
      myosatellite cells, interstitial cells and myofibres in mdx diaphragm contain
      accumulated or dotted LF granules, but only 12-20% of non-apoptotic cells contain
      LF. Apoptotic cells are very rare in the diaphragm of age-matched C57 control
      mice. This suggests that the regeneration of mdx diaphragm muscle initiated from
      myosatellite cells is impaired by their apoptosis as the result of either
      oxidative stress or a product of oxidative injury.

PMID- 11326749
TI  - Kat1-antigen--a reliable immunological marker for identifying osteoclast
      precursors of rats: detection of subpopulations among precursors and initiation
      of osteoclastogenesis.
AB  - Previously we found a unique cell surface antigen [Kat1-antigen (Kat1-Ag)]
      expressed on rat osteoclasts. In the present study, we focused on the expression
      of this antigen in preosteoclasts, mononuclear precursors of osteoclasts.
      Immunohistochemical and immunoelectron microscopic observations of the Kat1-Ag
      expressed in vivo showed the antigen to be present on mononuclear cells having
      the morphological features of preosteoclasts. The relationship between Kat1-Ag
      expression and calcitonin receptor (CTR) expression was examined in detail by a
      double-detection technique for CTR and Kat1-Ag by use of autoradiography and
      immunocytochemistry, respectively. In a culture system for forming mononuclear
      preosteoclast-like cells, almost 100% of the mononuclear cells expressing Kat1-Ag
      also expressed CTR, demonstrating that Kat1-Ag is a reliable immunological marker
      for identifying preosteoclasts. Interestingly, a significant number of the CTR
      positive mononuclear cells did not express the Kat1-Ag. Detection of these cells
      expressing CTR but not Kat1-Ag strongly suggests the presence of subpopulations
      in preosteoclasts. We also obtained evidence suggesting that expression of the
      Kat1-Ag is initiated during the postmitotic stage of the osteoclast progenitors.

PMID- 11326750
TI  - Fluorescent dyes for cell viability: an application on prefixed conditions.
AB  - In recent years increasing attention has been given to apoptosis for its role in
      pathologic, organogenetic and homeostatic phenomena. Acridine orange (AO),
      Hoechst 33342 (HO) and propidium iodide (PI) are among the most used fluorescent
      dyes used to analyse cell culture viability. In fact, they respectively show
      specificity for living, apoptotic and late apoptosis/necrosis states. We explored
      whether HO, AO and PI can be used on prefixed monolayers of three commonly used
      cell lines. Here we mainly describe the metachromatic effects obtained by
      fluorescence microscopy with double and triple dye combinations. Furthermore, we
      propose an easy staining method in which a balanced sequential treatment with HO,
      AO and PI allows identification of different viability states onto fixed cells by
      using a long-pass FITC filter. This method extends the spectrum of suitable
      applications for these dyes in fluorescence viability detection onto previously
      fixed (prefixed) samples.

PMID- 11326751
TI  - Expression of cell adhesion molecule T-cadherin in the human vasculature.
AB  - Alterations in expression of surface adhesion molecules on resident vascular and
      blood-derived cells play a fundamental role in the pathogenesis of cardiovascular
      disease. Smooth muscle cells (SMCs) have been shown to express T-cadherin (T
      cad), an unusual GPI-anchored member of the cadherin family of adhesion
      molecules. Particular relevance for T-cad in cardiovascular tissues is indicated
      by our present screen (immunoblotting) of human tissues and organs whereby
      highest expression of T-cad was found in aorta, carotid, iliac and renal arteries
      and heart. To explore the (patho)physiological role for T-cad in the vasculature
      we performed an immunohistochemical analysis of T-cad expression in normal human
      aorta and atherosclerotic lesions of varying severity. T-cad was present both in
      the intima and media and was expressed in endothelial cells (ECs), SMCs and
      pericytes, but not in monocytes/macrophages, foam cells and lymphocytes. In the
      adventitia T-cad was present in the wall of vasa vasorum and was expressed in
      ECs, SMCs and pericytes. T-cad was differentially expressed in SMCs from distinct
      vascular layers of normal aorta (for example, high in the subendothelial
      (proteoglycan) layer of the intima, low in the musculoelastic intimal layer and
      in the media), as well as at different stages of lesion progression. In SMCs
      there was an apparent inverse relationship between the intensities of T-cad and
      smooth muscle alpha-actin expression, this being most prominent in lesions. The
      findings suggest a phenotype-associated expression of T-cad which may be relevant
      to control of the normal vascular architecture and its remodelling during
      atherogenesis.

PMID- 11326752
TI  - Subcellular localization of Dp71 dystrophin isoforms in cultured hippocampal
      neurons and forebrain astrocytes.
AB  - It has been suggested that the absence or altered structure of Dp71, a C-terminal
      dystrophin gene encoded protein, is responsible for mental alterations observed
      in about 30% of Duchenne muscular dystrophy patients. Most of these patients have
      premature translational termination or point mutations at the C-terminal domain
      of this gene. In brain, Dp71 is the major protein product of the dystrophin gene.
      To determine the function of Dp71 isoforms in this organ, it is important to
      document their presence and intracellular localization in brain cells. Extracts
      from cultured hippocampal neurons and forebrain astrocytes and 5F3 and Dys 2
      monoclonal antibodies were thus used for western blots. In these conditions, two
      Dp71 isoforms spliced or not at exon 78 were detected in both cells (Dp71f and
      Dp71d, respectively). By immunocytochemistry, we mapped Dp71f and Dp71d in the
      Golgi complex (GC) and in neuronal nuclei. Only Dp71d was found in cytoplasmic
      neurofilaments. In astrocytes, these isoforms were detected in the GC. These cell
      localization data suggest that these Dp71 isoforms may have different functions
      in the same cell or organelle, as well as in the two different cells analyzed.

PMID- 11326753
TI  - Process formation of podocytes: morphogenetic activity of microtubules and
      regulation by protein serine/threonine phosphatase PP2A.
AB  - Podocytes possess major processes containing microtubules (MTs) and intermediate
      filaments and foot processes containing actin filaments (AFs) as core
      cytoskeletal elements. Although the importance of these cytoskeletal elements for
      maintaining podocyte processes was previously shown, so far no data are available
      concerning the developmental regulation of podocyte process formation. A
      conditionally immortalized mouse podocyte cell line, which can be induced to
      develop processes similar to those found in vivo, was treated with various
      reagents to disrupt cytoskeletal elements or to inhibit protein phosphatases. MTs
      colocalized with vimentin intermediate filaments but not with AFs. After AF
      disassembly, major processes were maintained, whereas after depolymerization of
      MTs, podocytes lost their processes, rounded up, and maintained only actin-based
      peripheral projections. Suppression of MT elongation by nanomolar vinblastine or
      inhibition of serine/threonine phosphatase PP2A with okadaic acid abolished
      process formation. PP2A was expressed in undifferentiated but not in
      differentiated podocytes. One- and two-dimensional western blot analyses revealed
      a dose-dependent increase in serine/threonine phosphorylation after okadaic acid
      treatment. Hence, morphogenetic activity of MTs induces podocyte process
      formation via serine/threonine protein dephosphorylation by PP2A. These results
      may open new avenues for understanding the signaling mechanism underlying
      podocyte cytoskeleton alterations during development and in glomerular diseases.

PMID- 11326754
TI  - Suicide and life-threatening behavior. Background papers to The National Suicide
      Prevention Conference. October 1998, Reno, Nevada, USA.

PMID- 11326755
TI  - Suicide among African American men.

PMID- 11326756
TI  - Suicidal behavior among Latino youth.

PMID- 11326757
TI  - Suicide prevention in American Indian and Alaska Native communities: a critical
      review of programs.

PMID- 11326758
TI  - Suicide in later life: a review and recommendations for prevention.

PMID- 11326759
TI  - Suicide in the medically ill.

PMID- 11326760
TI  - Youth suicide prevention.

PMID- 11326761
TI  - Consumers of mental health services.

PMID- 11326762
TI  - The relationship between sexual orientation and risk for suicide: research
      findings and future directions for research and prevention.

PMID- 11326763
TI  - Suicidology and the university: a founder's reflections at 80.

PMID- 11326764
TI  - Are UN peacekeepers at risk for suicide?
AB  - Media reports connecting UN peacekeeping duties by Canadian soldiers to their
      subsequent suicide prompted this study of peacekeeping as suicide risk. In a case
      control design we retrospectively compared 66 suicides in the Canadian military
      between 1990 and 1995 with two control groups: (a) 2,601 controls randomly
      selected from the electronic military database and (b) 66 matched controls with
      complete personnel and medical data. We found no increased risk of suicide in
      peacekeepers except among a subgroup of air force personnel. Here confounding
      individual factors, isolation from supports, and possibly inadequate preparation
      for deployment elucidated their suicides. Theater of deployment (e.g., Bosnia)
      did not affect the suicide rate. Military suicides experienced psychosocial
      stresses and psychiatric illness more often than their matched controls. We
      conclude that although peacekeeping per se does not increase overall suicide
      risk, military life-styles may strain interpersonal relationships, encourage
      alcohol abuse, and contribute to psychiatric illness and suicide in a minority of
      vulnerable individuals irrespective of peacekeeping assignment. Careful
      selection, and preparatory military training that encourages intragroup bonding
      and mutual support, may protect against suicide risk.

PMID- 11326765
TI  - A note concerning Durkheim's precedence in the use of the terms egoistic and
      altruistic suicide.

PMID- 11326766
TI  - Learnings from Durkheim and beyond: the economy and suicide.
AB  - This empirical study commemorates Durkheim's contribution to suicidology by
      reviewing his own and his followers' formulation of the relationship between the
      business cycle and suicide. Three distinctive sociological theories of suicide,
      including Durkheim's, were identified to link the suicide rate to the socio
      economic environment of the society. A real-income hypothesis of suicide was
      developed to capture (a) the positive impact of the economy on suicide, (b) the
      curvilinear impact of the economy on suicide implied by Durkheim's proposition,
      and (3) the interplay of both economic and sociological variables on suicide.
      Another implication from the reformulation is that there may exist a positive
      natural rate of suicide for any society. These two hypotheses were tested using
      the 1990 census data for the continental states of the United States. Some
      conclusions and suggestions were drawn for future research.

PMID- 11326767
TI  - Loneliness in relation to suicide ideation and parasuicide: a population-wide
      study.
AB  - Some links between loneliness and different manifestations of suicidal conduct
      have been reported in variety of subgroups (e.g., college students, the elderly,
      psychiatric patients). We tested this hypothesis by using the results of a
      population-wide survey. Strong associations among suicide ideation, parasuicide
      and different ways of being lonely and alone, defined either subjectively (i.e.,
      the feeling), or objectively (i.e., living alone or being without friends), were
      observed. Moreover, prevalence of suicide ideation and parasuicide increased with
      the degree of loneliness. Only minimal differences between men and women were
      found.

PMID- 11326769
TI  - An epidemiological profile of suicides in Beijing, China.
AB  - Suicide rates in the Beijing region increase with age. The rural suicide rate is
      about two to five times of the urban in various age-sex groups. The elderly
      suicide rate is very serious, especially in the rural area. The average suicide
      rate for the Beijing region for the period 1987-1996 was 9.8 per 100,000 (6.0 and
      17.3 for urban and rural areas, respectively). A low male-to-female ratio was
      also observed. The female suicide rate for the 15-34 age group was higher than
      that of its male counterparts, which is unique in other areas of the world. These
      phenomena can be explained by some of the distinct cultural and economic traits
      of China. Also, suicides rates in the Beijing region were shown to be on a
      decreasing trend among the teenaged and the old-age groups. Our findings suggest
      that the suicide rate in China should not be as high as the estimated rate (31.0
      per 100,000), suggested in the Global Health Statistics by Murray and Lopez
      (1996b, p. 824).

PMID- 11326768
TI  - Immediate post intervention effects of two brief youth suicide prevention
      interventions.
AB  - This study evaluated the immediate postintervention effects of two brief suicide
      prevention protocols: a brief interview--Counselors CARE (C-CARE)--and C-CARE
      plus a 12-session Coping and Support Training (CAST) peer-group intervention.
      Subjects were students "at risk" of high school dropout and suicide potential in
      Grades 9-12 from seven high schools (N = 341). Students were assigned randomly to
      C-CARE plus CAST, C-CARE only, or "intervention as usual." The predicted patterns
      of change were assessed using trend analyses on data available from three
      repeated measures. C-CARE and CAST led to increases in personal control, problem
      solving coping, and perceived family support. Both C-CARE plus CAST and C-CARE
      only led to decreases in depression, and to enhanced self-esteem and family goals
      met. All three groups showed equivalent decreases in suicide risk behaviors,
      anger control problems, and family distress.

PMID- 11326770
TI  - Personal and professional factors and suicide intervention skills.
AB  - This research investigated the relationship of professional and personal factors
      to the ability of counselors to respond appropriately to suicidal verbalizations
      using the Suicide Intervention Response Inventory (SIRI). Level of training,
      experience with suicidal clients, and death acceptance were positively related to
      suicide intervention competencies. A personal history of suicidality and a belief
      that suicide is a personal right were negatively related to such skills.
      Regression analysis revealed that personal history of suicidality and attitude
      toward suicide as a personal right accounted for a modest, but significant,
      percentage of the variance in SIRI scores, beyond that accounted for by
      professional factors. Post hoc analysis indicated that the negative relationship
      between personal history of suicidal behaviors and suicide counseling skills was
      significant in the professionally trained participants. These results highlight
      the importance of attitudes toward suicide and personal history of suicidality,
      as well as training and experience, in effectively counseling potentially
      suicidal clients.

PMID- 11326771
TI  - Do they suffer more? Reflections on research comparing suicide survivors to other
      survivors.
AB  - This article contrasts public perceptions of suicide survivors with conclusions
      based on comparative studies of suicide, fatal accident survivors, and other
      survivors. Although suicide is commonly thought to cause a particularly burden
      some grief, quantitative studies have often failed to support this. We then offer
      some interpretations of these findings and suggest future pathways for research.

PMID- 11326772
TI  - Are closed-minded people more open to the idea of killing themselves?
AB  - This article summarizes the author's work on Openness to Experience (a
      personality trait) and suicidal behavior. It appears that people who obtain low
      scores on an inventory measuring Openness to Experience are less likely to report
      suicidal ideation but more likely to take their own lives. How can this apparent
      discrepancy be reconciled? Based on the premise that the expression of suicidal
      ideation can have adaptive consequences (e.g., by mobilizing family and treatment
      providers), it is hypothesized that people with major depression who are low in
      Openness may be at increased risk for completed suicide in part because they are
      less likely to feel, or report feeling, suicidal.

PMID- 11326773
TI  - Is suicide bereavement different? A reassessment of the literature.
AB  - The question of whether suicide bereavement is different from mourning after
      other types of deaths has important theoretical and clinical implications. Some
      recent literature reviews have argued that the differences may be minimal. In
      contrast, this article suggests that suicide bereavement is distinct in three
      significant ways: the thematic content of the grief, the social processes
      surrounding the survivor, and the impact suicide has on family systems. In
      addition, problems in the methodology used to compare different bereavement
      experiences are addressed. Some clinical implications of these conclusions,
      including the need for homogeneous support groups, psychoeducational services,
      and family and social network interventions are also discussed.

PMID- 11326774
TI  - Legal implications of hormesis.

PMID- 11326775
TI  - Getting ahead of ourselves: a comment on Professor Cross's legal implications of
      hormesis.

PMID- 11326776
TI  - The hormesis challenge for environmental health regulators.

PMID- 11326777
TI  - Regulatory implementation and indeterminate hormesis effects.

PMID- 11326778
TI  - A regulatory precedent for hormesis.

PMID- 11326779
TI  - Hormesis and the law.

PMID- 11326780
TI  - The cost of reducing scientific uncertainty concerning hormesis: a commentary on
      Professor Cross's paper.

PMID- 11326781
TI  - Hormesis and the radical moderation of law.

PMID- 11326782
TI  - The instability of the standard justification for physician-assisted suicide.

PMID- 11326783
TI  - Cultural engagement in clinical ethics: a model for ethics consultation.

PMID- 11326784
TI  - Informed consent: does it take a village? The problem of culture and truth
      telling.

PMID- 11326785
TI  - Jehovah's Witnesses and medical practice in Mexico: religious freedom, parens
      patriae, and the right to life.

PMID- 11326786
TI  - Bioethics in Eastern Europe: a difficult birth.

PMID- 11326787
TI  - Ancestors, computers, and other mixed messages: ambiguity and euthanasia in
      Japan.

PMID- 11326788
TI  - Cultural collisions at the bedside: social expectations and value triage in
      medical practice.

PMID- 11326789
TI  - What is wrong with global bioethics? On the limitations of the four principles
      approach.

PMID- 11326790
TI  - Abortion, disability, assent, and consent.

PMID- 11326791
TI  - Challenges and conflicts in pain management.

PMID- 11326792
TI  - Educating ourselves and educating patients.

PMID- 11326794
TI  - Nutrition and women's health: the politics of dietary advice.

PMID- 11326793
TI  - Treading carefully on the moral high ground.

PMID- 11326795
TI  - Dietary trends among low socioeconomic status women of childbearing age in the
      United States from 1977 to 1996: a comparison among ethnic groups.
AB  - OBJECTIVE: To identify dietary trends among low socioeconomic status women of
      childbearing age from three ethnic groups from 1977 to 1996. METHODS: The sample
      consisted of 19- to 44-year-old women at 185% of poverty with 12 years of
      education or less (n = 4682) from three US Department of Agriculture surveys. The
      Revised Diet Quality Index (DQI-R) and level of folate were the main outcomes
      measured. Changes in food consumption for several food groups were also examined.
      RESULTS: Diet quality significantly improved between 1977 and 1996 for Hispanics
      and non-Hispanic whites. All groups had significant decreases in saturated fat
      intake by 1996, but only Hispanic and non-Hispanic white women significantly
      decreased their total fat and cholesterol intakes. Fruit and vegetable intakes
      remained stable. Mean intakes of calcium, iron, and folate were below
      recommendations at every time point for all ethnic groups. All three groups
      decreased their intakes of butter, margarine, egg items, bacon, high-fat red
      meats, and low-fiber/high-fat breads and increased their intakes of high-fiber
      cereals, all of which are positive. These trends were balanced, however, by
      decreases in medium-fiber vegetables, soy, and legumes and increases in high
      fat/high-fiber breads, high-fat desserts, high-fat salty snacks, and high-fat
      grain-based mixed dishes. CONCLUSIONS: This study highlights problem dietary
      habits that public health professionals need to address in order to reduce the
      prevalence of diet-related chronic diseases.

PMID- 11326796
TI  - Calcium intake and peak bone mass.
AB  - Studying the relationship between calcium intake and peak bone mass in adolescent
      women is complicated by several factors. Calcium intake and calcium absorption
      are interrelated and can vary widely for the same individual, as well as among
      individuals. Modifiable determinants that affect bone gain in the peripheral
      skeleton do not necessarily have the same effect on the axial skeleton. In
      addition to these physiological factors, differences in study design make
      comparisons difficult. Study cohorts have varied in age, size, and pubertal
      status; bone measurements have been made at different sites with different
      equipment; and calcium intakes have been measured in different ways. Other
      important variables include endocrine maturation patterns and physical activity
      levels. Given this complex relationship, the amount of calcium young women need
      to achieve peak bone mass remains unclear. There is no convincing evidence,
      however, that they need more than 900 mg/day.

PMID- 11326797
TI  - Pregnancy weight gain and postpartum loss: avoiding obesity while optimizing the
      growth and development of the fetus.
AB  - Weight gain during pregnancy may contribute to obesity development. Concerns
      about possible adverse effects of pregnancy weight gain on later maternal weight
      and on labor and delivery must be rigorously evaluated in light of possible
      benefits for fetal growth and development. Birth-weight rises with increased
      pregnancy weight gain, and perinatal and neonatal mortality fall as birthweight
      increases in both preterm and term infants. The lowest mortality is observed at
      3500 to 4500 g in infants of white women. Although often thought to be at high
      risk, infants termed "macrosomic" include infants of the lowest mortality rate.
      Thus, restricting weight gain may be detrimental to the baby. Weight gain that is
      optimal for the mother and the baby differs according to the mother's
      prepregnancy weight. Pregnancy weight gain exceeding current recommendations is
      associated with increases in maternal fat gain, pregnancy complications, and
      delivery problems and should be discouraged. Postpartum weight loss is essential
      to prevent permanent weight increase. Smoking cessation during pregnancy, reduced
      postpartum physical activity, and other lifestyle changes can contribute to
      increased postpartum weight. Health care providers can help to reduce obesity
      risk by regularly monitoring women's weight; promoting appropriate prepregnancy
      weight, pregnancy weight gain, and postpartum weight less; and explicitly
      encouraging maintenance of an active postpartum lifestyle.

PMID- 11326798
TI  - Developing comprehensive approaches to prevention and control of obesity among
      low-income, urban, African-American women.
AB  - Obesity presents a major threat to the health and well-being of low-income,
      urban, African-American women. African-American women have among the highest
      rates of obesity in the United States and suffer from a corresponding excess
      burden of obesity-related diseases. Distinct physiological, societal, cultural,
      and environmental factors form a mosaic of forces that promote weight gain and
      prevent weight loss in these women. To develop specific strategies to improve
      their health, researchers need to better understand the unique nutritional
      problems facing low-income African-American women residing in inner cities.
      Individual and community interventions to promote weight reduction have been
      insufficient to reverse the epidemic. A problem of this magnitude requires
      concerted and comprehensive policy interventions. This paper uses an ecological
      approach to suggest multilevel public health strategies to reduce obesity among
      urban African-American women.

PMID- 11326799
TI  - Screening for receipt of WIC benefits during pregnancy: feasible or illusory?
AB  - The US Department of Agriculture has contracted with the National Academy of
      Sciences to convene an expert panel to create and refine dietary criteria for
      entry into the Special Supplemental Food Program for Women, Infants and Children
      (WIC). This paper explores the technical requirements for successful screening
      under the assumption that the criterion for receipt of program benefits for
      pregnant women is the prevention of low birthweight. To succeed, the proposed
      screening program would have to: identify women likely to bear low birthweight
      infants, offer an intervention that can reverse low birthweight, and distinguish
      women who are likely to be responsive to the intervention from those who are not.
      It appears that these requirements are impossible to meet at this time, and it is
      unlikely they can be met in the foreseeable future. It is suggested that
      nutrition education may be a more appropriate application for dietary assessment,
      and that screening and education cannot optimally be done simultaneously.

PMID- 11326800
TI  - Health at any size: the size-acceptance nondiet movement.
AB  - A controversial new approach to obesity treatment has emerged during the last two
      decades in response to traditional programs that do not result in sustained
      reductions in weight. Goals of the size-acceptance nondiet movement include
      improving self-image, normalizing eating behavior, and increasing physical
      activity independent of body weight. This commentary presents the basic tenets
      and early voices in the movement, reviews government weight recommendations, and
      suggests strategies for the size-sensitive physician.

PMID- 11326801
TI  - Nutrition and women's health: challenge for the 21st century.
AB  - The recent release of Healthy People 2010 and the Dietary Guidelines for
      Americans were significant events, especially for the nutritional health of
      women. Given the number of women diagnosed with nutrition-related diseases and
      the increasing cultural diversity of the US population, implementing the dietary
      recommendations poses challenges for women clinicians. Clinicians must recognize
      and respect the cultural beliefs, behaviors, and traditions of their female
      patients if the goals of a healthy diet are to be achieved. And culturally
      sensitive interventions are needed to reduce women's risk of developing nutrition
      related diseases over the next decade.

PMID- 11326802
TI  - How can clinicians approach nutrition?
AB  - A clinician reflects on how nutrition and exercise assessments are integral to
      the care of patients with diabetes and, more broadly, how these assessments can
      increase understanding of the patient. Nutrition, metabolic control, self-esteem,
      and self-care are often intertwined. Using a team approach and acknowledging
      patient effort and attitude change can help patients modify lifestyle patterns,
      although the road to change may be slow. Exercise counseling should be part of
      nutrition recommendations. Poor nutritional habits represent a major challenge to
      improving health status and will require the coordinated efforts of health care
      providers and other stakeholders in society.

PMID- 11326803
TI  - Science and advocacy as partners: the Office of Research on Women's Health in the
      1990s.
AB  - The federal government's investment in research related to sex/gender differences
      in health and disease has resulted in better understanding of the health of women
      and men and holds promise for improved health. By working together, advocates for
      women's health and the scientific community have expanded the focus of women's
      health research and created new opportunities in science. The Office of Research
      on Women's Health has assessed and identified progress and needs in women's
      health in its Agenda for Research on Women's Health for the 21st Century and will
      continue to collaborate with the advocacy and scientific communities to keep
      women's health research a high national priority that is responsive to changing
      public health needs.

PMID- 11326804
TI  - Post-traumatic stress disorder in extremely poor women: implications for health
      care clinicians.
AB  - OBJECTIVES: To identify childhood antecedents for lifetime post-traumatic stress
      disorder (PTSD) and to determine how this diagnosis relates to health and service
      use among extremely poor women. METHODS: We conducted a secondary data analysis
      of 425 women in the Worcester Family Research Project, a case-control
      longitudinal study of 220 sheltered homeless and 216 extremely poor housed (never
      homeless) women in Worcester, Massachusetts. RESULTS: We found that extremely
      poor women with lifetime PTSD were more likely to have grown up in family
      environments of violence, threat, and anger than those without PTSD. The
      strongest risk factor for PTSD was childhood sexual abuse with threat. Low-income
      women with lifetime PTSD had more bodily pain, even when controlling for other
      health and demographic factors. Women with PTSD experienced more chronic health
      conditions and had more problematic relationships with their health care
      providers and perceived more barriers to care. CONCLUSION: Many low-income women
      have difficulty using medical care appropriately because of childhood histories
      of physical and sexual abuse, the subsequent development of post-trauma
      responses, and structural barriers to care. Given these factors, it is critical
      that health care clinicians routinely screen for histories of violence and PTSD
      and develop treatment plans that ensure safety, link current symptoms with prior
      experiences, and provide support as necessary. A team approach coordinated by a
      case manager may be the best strategy. Without routine screening for PTSD and
      sensitive treatment, many extremely poor women will receive compromised health
      care and may even be retraumatized.

PMID- 11326805
TI  - Should patients with documented or probable coronary artery disease routinely be
      placed on beta-blockers before noncardiac surgery?

PMID- 11326806
TI  - Can fibromyalgia and chronic fatigue syndrome be cured by surgery?

PMID- 11326807
TI  - Should an ACE inhibitor be stopped if signs of renal insufficiency appear?

PMID- 11326808
TI  - Performance-enhancing substances: what athletes are using.
AB  - Use of performance-enhancing substances is widespread among competitive athletes,
      whether professional or amateur, adolescent or adult. Some of these substances
      are legal and beneficial, but others are illegal or have adverse or unproven
      effects. This article describes the action and effects of these substances, their
      legality, and their potential for abuse.

PMID- 11326809
TI  - Falls in elderly patients: predictable and preventable.
AB  - Accidental falls are a preventable cause of serious injuries and death in the
      elderly. Recent studies have identified a number of risk factors for falls,
      including sedative use, cognitive impairment, lower extremity weakness, and
      impaired vision. Office evaluation that focuses on finding the cause helps to
      identify what interventions are needed to prevent recurrent falls.

PMID- 11326810
TI  - Finding evidence-based answers to clinical questions online.
AB  - You can find evidence-based answers to clinical questions quickly by searching
      online medical databases. The key is to be selective, on the basis of the type of
      information you need. Online textbooks, consensus guidelines systematic reviews,
      and MEDLINE are all available.

PMID- 11326811
TI  - Legionnaires' disease: seek and ye shall find.
AB  - Legionella pneumophila is among the top three or four microbial causes of
      community-acquired pneumonia, yet is often misdiagnosed and inadequately treated.
      New laboratory tests should simplify the diagnosis. Also, contrary to common
      perception, the disease is usually spread via aspiration of water from
      contaminated hot water distribution systems, not from air conditioning systems.
      The treatment of choice has shifted from erythromycin to the newer macrolides and
      quinolones. Routine culturing of the hospital water supply is a requisite first
      step in preventing hospital-acquired Legionnaires' disease.

PMID- 11326812
TI  - Handwashing compliance: what works?
AB  - Health care personnel--particularly physicians--do a poor job of complying with
      national handwashing guidelines, yet handwashing is the cornerstone of infection
      control. New products designed to increase compliance are available, such as
      automated handwashing machines, but their clinical benefits have not been fully
      studied. The best solution for now may be to continue awareness campaigns and
      education programs, ensure access to sinks and appropriate antiseptic products,
      and promote the use of alcohol disinfectants when handwashing is not possible.
      KEY POINTS: Antiseptic products are now preferred over handwashing with plain
      soap, which does not reliably prevent transmission of bacteria. Because 100%
      compliance may not be realistic, interventions that improve compliance, such as
      the use of alcohol sanitizing products when handwashing is not possible, may be
      the best solution. A number of barriers deter compliance, including lack of
      access to handwashing stations and lack of time. Gloves are not a substitute for
      handwashing because they are not fully protective.

PMID- 11326813
TI  - Immunizations in adult immunocompromised patients: which to use and which to
      avoid.
AB  - Immunization is important to protect immunocompromised patients from preventable
      infectious disease but is often underused. Although live vaccines are
      contraindicated for most immunocompromised patients, many killed or component
      vaccines are safe and recommended. Vaccines may sometimes induce suboptimal
      immunogenicity, but even partial protection may benefit severely ill patients.
      KEY POINTS: Vaccines against Streptococcus pneumoniae and influenza are strongly
      recommended for most immunosuppressed patients. When possible, immunization
      series should be completed before procedures that require or induce
      immunosuppression, such as organ transplantation or chemotherapy. If this is not
      possible, the patient may mount only a partial immune response, but even this
      partial response can be beneficial. Patients who undergo allogeneic bone marrow'
      transplantation lose preexisting immunities against a variety of diseases and
      should be revaccinated. In many situations, family members should be vaccinated
      to protect the patient. However, oral live polio vaccine should be avoided
      because it may carry the risk of infecting the patient.

PMID- 11326814
TI  - Safe use of sildenafil in patients with coronary artery disease.
AB  - Despite isolated reports of myocardial infarction and sudden cardiac death in men
      taking sildenafil for erectile dysfunction, clinical evidence shows the drug to
      be safe, effective, and well tolerated in most men with coronary artery disease.
      Nevertheless, caution is advised in specific instances.

PMID- 11326815
TI  - Dofetilide (Tikosyn): a new drug to control atrial fibrillation.
AB  - Dofetilide, a new class III antiarrhythmic agent, selectively blocks a specific
      cardiac potassium channel, IKr, increasing the effective refractory period of the
      myocyte and thereby terminating reentrant arrhythmias. Given orally, it appears
      to effectively convert atrial fibrillation and atrial flutter to sinus rhythm and
      maintain sinus rhythm after conversion in appropriately selected patients. This
      paper reviews the pharmacology of dofetilide, the evidence of its effectiveness,
      and the appropriate precautions in using it. KEY POINTS: Dofetilide is generally
      well tolerated but like other class III drugs can cause torsades de pointes. The
      risk is dose-dependent and can be minimized by adjusting the dosage according to
      creatinine clearance and QT interval, by excluding patients with known risk
      factors for long QT syndrome and torsades de pointes, and by starting treatment
      in an inpatient monitored setting for the first 3 days. Unlike other
      antiarrhythmic agents, oral dofetilide did not increase the mortality rate in
      clinical studies in postmyocardial infarction patients or those with congestive
      heart failure at high risk for sudden cardiac death. Concomitant use of drugs
      that increase the plasma level of dofetilide is contraindicated; these include
      cimetidine, ketoconazole, trimethoprim-sulfamethoxazole, and verapamil.

PMID- 11326816
TI  - The clinical significance of interactions between HIV and TB: more questions than
      answers.

PMID- 11326817
TI  - Historical declines in tuberculosis: nature, nurture and the biosocial model.
AB  - The large declines in the incidence of tuberculosis over time in the industrially
      developed nations have usually been attributed to natural selection or to socio
      economic improvements. Both explanations are beset with problems, as there is
      little firm evidence for the occurrence of natural selection of resistance to
      tuberculosis to any significant extent, and doubts have been expressed as to
      whether the incidence of a disease can be directly related to measures of socio
      economic change without consideration of the impact of the many specific public
      health measures that have been taken. In addition, analyses of the changing
      prevalence of tuberculosis must consider the impact of changing environmental and
      ecological factors that affect, for example, the immunising effect of exposure to
      Mycobacterium bovis and saprophytic mycobacteria. It is also necessary to
      determine whether the causative organism is undergoing evolutionary change, as
      recent reports suggest.

PMID- 11326818
TI  - Revised international definitions in tuberculosis control.

PMID- 11326819
TI  - Spacer oligonucleotide typing of bacteria of the Mycobacterium tuberculosis
      complex: recommendations for standardised nomenclature.
AB  - Spacer oligonucleotide typing (spoligotyping) is widely used for differentiation
      of bacteria of the Mycobacterium tuberculosis complex. However, the absence of
      any standardised method for concise description of spoligotypes makes it
      difficult to compare the results from different laboratories. This paper
      describes unambiguous, interconvertible systems for the designation of
      spoligotype patterns, the adoption of which will be beneficial to mycobacterial
      research.

PMID- 11326820
TI  - Attention to gender issues in tuberculosis control.
AB  - Although a seventy per cent excess of male over female TB cases are reported
      globally each year, the reasons for this difference are unclear. Generally, women
      in poor countries confront more barriers than men in accessing health care
      services. Yet, research is lacking to explain the impact of gender inequalities
      in access to care on reported sex ratios for TB. A review of the limited
      available literature and field visits to TB programmes offered insights and
      suggested a framework to study gender differentials in TB. This paper considers
      the role of gender at various steps in effective TB care. A research strategy to
      study and account for gender differences in TB control is proposed.

PMID- 11326821
TI  - Association between tuberculosis and HIV disease progression in a high
      tuberculosis prevalence area.
AB  - SETTING: Adult human immunodeficiency virus (HIV) clinics affiliated to the
      University of Cape Town, South Africa. OBJECTIVE: To assess the impact of
      tuberculosis on HIV-1 disease progression in an area with high tuberculosis
      prevalence and minimal antiretroviral therapy use. DESIGN: Prospective patient
      cohort study. METHODS: Age, race, risk status, CD4+ T-lymphocyte count, history
      of AIDS, prophylactic co-trimoxazole and antiretroviral therapy were controlled
      for in a time-dependent Cox proportional hazards regression model. RESULTS:
      Tuberculosis fulfilling the case definition developed in 158/609 patients in the
      5-year observation period. Tuberculosis was associated with an increased risk of
      AIDS (adjusted risk ratio [RR] = 1.60, 95% confidence interval [CI] 1.08-2.41; P
      = 0.02) and death (adjusted RR = 2.16, 95% CI 1.29-3.59; P = 0.003). In a
      stratified analysis, the increased mortality associated with tuberculosis was
      observed only in patients with CD4+ T-lymphocyte count > 200 cells/microliter and
      in those without AIDS at baseline. CONCLUSION: The onset of tuberculosis in HIV
      infected patients is associated with an increased risk of AIDS and death.
      Although a causal link cannot be established in an observational study, our
      findings support the view that prolonged immune activation induced by
      tuberculosis leads to prolonged increased HIV replication and consequent
      accelerated disease progression.

PMID- 11326822
TI  - Factors affecting time delay to treatment in a tuberculosis control programme in
      a sub-Saharan African country: the experience of The Gambia.
AB  - SETTING: Rural and urban health centres in The Gambia, West Africa. OBJECTIVES:
      To estimate the time delay between onset of symptoms and initiation of treatment
      and identify the risk factors influencing the delay in patients with tuberculosis
      (TB). DESIGN: Structured interviews with newly diagnosed TB patients aged over 15
      years presenting to TB control staff in four health centres. RESULTS: A total of
      152 TB patients were interviewed. The median delay from onset of symptoms to
      commencement of treatment was 8.6 weeks (range 5-17). Delay to treatment was
      independent of sex, but was shorter in young TB patients. The median delay was
      longer in rural than in urban areas (12 weeks [range 8.5-17] vs. 8 [4-12], P <
      0.01) and in those who did not attend school, but this effect disappeared after
      adjusting for age and area of residence. Patients who reported haemoptysis as one
      of their initial symptoms had shorter delays to treatment. There was no relation
      between duration of delay to treatment and cure rate, but longer delay did
      increase the risk of death. CONCLUSION: Starting TB patients on treatment as
      early as possible plays a major role in reducing disease transmission in the
      community. Key to this is increasing awareness of the signs and symptoms of TB
      and ensuring easy access to diagnostic facilities and treatment.

PMID- 11326823
TI  - Survey for tuberculosis in a tribal population in North Arcot District.
AB  - SETTING: Tribal villages in the jungles of the Jawadhu hills, South India.
      OBJECTIVE: To estimate the prevalence of tuberculosis (TB) infection and disease
      in a remote tribal population. DESIGN: A cross-sectional survey with two-stage
      screening for identification of cases. A stratified probability proportional
      sample with the hamlet as the unit. METHODS: Among 56 revenue divisions with a
      population of about 66,000, 24 revenue divisions were selected. Among 26,320
      persons registered, children < 10 years were tuberculin tested and reactions were
      read after 72 hours. Those over 15 were X-rayed, and tuberculosis symptoms were
      investigated. Sputum was collected from those with abnormal X-ray or symptoms and
      examined for smear and culture positivity and sensitivity. RESULTS: Of the 6952
      children tested and read, 5% had BCG scars and the prevalence of infection was
      5%. The annual risk of infection was 1.1. Among adults, the prevalence of
      bacillary cases was 8/1000 and X-ray cases 29/1000. The prevalence of bacillary
      disease was higher among males, particularly with increasing age. Thirty
      symptomatic cases had normal X-rays and 63 X-ray cases had no symptoms. Thus
      prevalence would have been underestimated if either method had been used alone
      for screening. Isoniazid resistance was seen in 12% of patients, two of whom also
      had rifampicin resistance (2.6%). CONCLUSIONS: The prevalence and pattern of
      tuberculosis in this tribal group is similar to that observed in non-tribal
      areas.

PMID- 11326824
TI  - Is quarterly cohort analysis useful for assessing treatment outcomes in a low
      incidence country?
AB  - SETTING: In the Czech Republic, a country regarded as having a low incidence of
      tuberculosis (TB), short-course chemotherapy (SCC) of TB has been implemented in
      routine practice country-wide. OBJECTIVE: To assess the outcome of SCC by
      quarterly cohort analysis of patients using the methodology recommended by the
      World Health Organization (WHO). DESIGN: Patients with newly detected
      bacteriologically confirmed pulmonary TB notified in 1998 were treated according
      to local recommendations (SCC) or with the WHO-recommended DOTS strategy. The
      type of chemotherapy and its outcome were evaluated 12 months later by quarterly
      cohort analysis. RESULTS: A total of 731 patients with bacteriologically
      confirmed pulmonary TB, 403 of them smear-positive, were assessed. The proportion
      of those treated under the DOTS strategy increased from 56.2% to 75.1%.
      Favourable treatment outcomes (cure or treatment completed) were achieved in
      69.0% of patients in the first quarter and 74.0% in the fourth quarter. Only four
      treatment failures and 21 defaulters were recorded. A total of 129 patients (15
      21% in different cohorts) died before or during treatment, mostly from causes not
      connected with TB. If this proportion were not taken into account, treatment
      efficacy would have attained 85%. CONCLUSIONS: Analysis of SCC based on quarterly
      cohorts proved feasible in routine conditions in a country with a low incidence
      of TB and ongoing TB control, and provided more information than once yearly
      analysis.

PMID- 11326825
TI  - Doubling of the tuberculosis incidence in Greenland over an 8-year period (1990
      1997).
AB  - OBJECTIVE: To determine the trends in conventional and molecular epidemiology of
      tuberculosis (TB) in Greenland over an 8-year period. DESIGN: A nation-wide,
      retrospective, population-based study of all cases of TB reported to the National
      Health Division of Greenland from 1 January 1990 to 31 December 1997. An analysis
      of microbiology data including RFLP results. RESULTS: The annual incidence
      increased from 85/100,000 in 1990 to 172/100,000 in 1997; 335 (72%) of the cases
      were culture-positive. On average 58% of culture-positive cases were smear
      positive, with an increase from 40% in 1990 to 69% in 1997. There was a
      significant increase in childhood TB from four cases in 1990 to 26 in 1997. RFLP
      analysis shows that 15% of the patients were infected with unique strains and 85%
      were infected with strains belonging to one of 20 clusters. There were four major
      clusters, comprising respectively 52, 34, 26 and 14 patients. CONCLUSION: There
      was a dramatic increase in TB cases in Greenland from 1990 to 1997. The increase
      is due to micro-epidemics in small isolated settlements, and affects primarily
      young adults and children. RFLP analysis confirms this observation and indicates
      confined, local transmission. In this context RFLP is not useful as the only
      parameter for monitoring recent transmission.

PMID- 11326826
TI  - Shifting the balance between in-patient and out-patient care for tuberculosis
      results in economic savings.
AB  - SETTING: Although hospitalisation is not always necessary for the treatment of
      tuberculosis (TB), in Australia 90% of TB patients have treatment initiated in
      hospital. OBJECTIVE: To calculate and compare the costs of in-patient and out
      patient tuberculosis treatment, and to measure the impact of shifting care from
      in-patient to out-patient settings. METHODS: In a costing study performed in
      Victoria, Australia, the proportion of all notified TB cases who were
      hospitalised was calculated by matching coded state hospital morbidity data with
      the Victoria Notifiable Diseases database for the financial year 1994-1995. In
      patient and out-patient costs were calculated using data obtained from a number
      of sources. The effect on health care costs of varying the proportion of TB cases
      treated as in-patients and out-patients was calculated using Excel. RESULTS:
      Nearly 90% (239/269) of notified TB cases received hospitalised care in 1994
      1995. The cost of treatment for hospitalised patients (mean length of stay 2
      weeks) was AU$5447 per patient, with a total cost of $1,301,833. Hospitalisation
      comprised 60% of the total cost of treatment. The cost of out-patient treatment
      was $2260 per patient. If 90% of patients were treated on an out-patient basis,
      the total cost would be $693,670. We estimated that it would be feasible to treat
      at least 55% of TB patients as out-patients, reducing costs by nearly 30%.
      CONCLUSIONS: Routine hospitalisation for patients with uncomplicated TB is not
      necessary, but is often used in industrialised countries. More cost-effective use
      of resources can be achieved by giving initial TB treatment on an out-patient
      basis rather than in hospital for a greater proportion of cases.

PMID- 11326827
TI  - Pulmonary resection in the treatment of patients with pulmonary multidrug
      resistant tuberculosis in Taiwan.
AB  - SETTING: Chronic Disease Control Bureau, Department of Health, Taiwan. OBJECTIVE:
      To evaluate the role of pulmonary resection in the treatment of pulmonary
      tuberculosis resistant to isoniazid and rifampin (MDR-TB). DESIGN: In a
      retrospective cohort study, 27 MDR-TB patients who underwent pulmonary resection
      between December 1990 and March 1999 were reviewed. Individually-tailored
      treatment regimens were selected at a once-weekly staff conference following
      review of the patient's case history and drug susceptibility results. Surgery was
      performed for selected patients, essentially those: 1) whose medical treatment
      had failed, or for whom treatment failure seemed highly likely, or for whom post
      treatment relapse seemed likely, 2) with predominantly localised disease, 3) with
      adequate cardiopulmonary reserve, and 4) whose treatment regimen had been
      composed of at least two effective drugs to diminish the mycobacterial burden.
      RESULTS: There was no surgical mortality apart from one peri-operative death
      (4%). Three patients (11%) developed complications, and 24 (92%) patients
      demonstrated sputum conversion and/or remained negative after surgery. Twenty
      three patients have already completed treatment, and during a mean of 42 +/- 18
      follow-up months (range 15-80 months), one patient relapsed. This patient was
      disease-free after another course of treatment. CONCLUSION: For selected
      patients, pulmonary resection may improve the outcome of pulmonary MDR-TB.

PMID- 11326828
TI  - Intrapulmonary pharmacokinetics of ofloxacin in drug-resistant tuberculosis.
AB  - OBJECTIVE: To determine the lung epithelial lining fluid (ELF) and serum levels
      of ofloxacin in drug-resistant tuberculosis patients during treatment. DESIGN:
      Ten drug-resistant tuberculosis patients treated with ofloxacin containing
      regimens for at least 2 weeks were enrolled in the study. Subjects ingested
      ofloxacin 10 mg/kg and other anti-tuberculosis agents after overnight fasting.
      RESULTS: Serum and bronchoalveolar lavage fluid were collected at 4 hours after
      treatment and assayed by high performance liquid chromatography. The mean
      concentrations of ofloxacin in serum and ELF were 5.889 +/- 1.096 and 16.583 +/-
      8.697 mg/L, respectively. The mean ratio of ELF-to-serum ofloxacin concentration
      was 2.825 +/- 1.275. CONCLUSION: Ofloxacin can penetrate well into the intra
      alveolar fluid of patients treated for drug-resistant tuberculosis. The lung ELF
      concentrations were consistently higher than the minimal inhibitory
      concentrations of Mycobacterium tuberculosis as determined in vitro.

PMID- 11326829
TI  - Upregulation of inducible nitric oxide synthase and cytokine secretion in
      peripheral blood monocytes from pulmonary tuberculosis patients.
AB  - SETTING: Peripheral blood monocytes (PBM) are the main source of alveolar
      macrophages, which have an upregulation of inducible nitric oxide synthase (iNOS)
      in pulmonary tuberculosis (TB). TNF-alpha and IL-1 beta are thought to be
      involved in the immune response to mycobacterial infection. OBJECTIVE: To
      identify whether iNOS expression and cytokine release of PBM are upregulated and
      have a connection in TB infection. DESIGN: The expression of iNOS
      immunoreactivity on PBM from TB patients and normal subjects was measured by
      loading with anti-macrophage iNOS polyclonal primary antibody analyzed by flow
      cytometry. Expression of iNOS mRNA in PBM was detected by RT-PCR. The spontaneous
      generation of nitrite and cytokines (IL-1 beta and TNF-alpha) by cultured
      monocytes was also determined. RESULTS: Compared to normal subjects, iNOS immuno
      reactivity, the capacity for spontaneous nitrite generation and the level of TNF
      alpha or IL-1 beta secretion of PBM were significantly higher in TB patients. The
      amount of nitrite, TNF-alpha and IL-1 beta released from PBM of TB patients was
      inhibited by NG-monomethyl-L-arginine (L-NMMA), a competitive inhibitor of NOS.
      The level of iNOS immunoreactivity on PBM was highly correlated with nitrite
      generation both in all the subjects studied and in TB patients alone. Spontaneous
      TNF-alpha production showed a stronger correlation with nitrite production than
      with IL-1 beta. CONCLUSION: The NO and cytokine synthase activities of monocytes
      appear to be concomitantly upregulated in response to mycobacterial infection.
      The enhanced NO generation by monocytes in TB patients may play an autoregulatory
      role in amplifying the synthesis of pro-inflammatory cytokines.

PMID- 11326830
TI  - The dynamics of cigarette smoking during military service in Syria.
AB  - SETTING: Understanding the dynamics of smoking in different populations is
      important to be able to tackle this problem rationally. DESIGN: A cross-sectional
      survey in a military school near Aleppo. Three groups of recruits were studied
      (total number of participants 596). The mean age of new draftees (group I) was
      19.8 +/- 0.02 years, that of draftees after 6 months of service (group II) was
      19.7 +/- 0.02 years, and that of draftees after 2 years of service (group III)
      was 21 +/- 0.02 years. RESULTS: Current and daily smoking was observed among
      respectively 46.1% and 34.1% of participants. Daily smokers smoked 17.8 +/- 0.7
      cigarettes per day. Within a 2-year interval, current smoking increased from
      43.2% to 55.1% (P = 0.01), and daily consumption from 15 to 23.8 cigarettes/day
      (P < 0.001). Smoking among draftee groups I and II was compared with age-matched
      male university students (314 first year students aged 19.1 +/- 0.04 years and
      262 third year students aged 21.3 +/- 0.05 years). Current smoking among recruits
      was higher at entry and after 2 years than that of age-matched civilians (P <
      0.001), but the 2-year increase was not (P > 0.05). CONCLUSION: Although military
      service in Syria is a scene of intensive smoking dynamics, it cannot be
      implicated in creating smokers.

PMID- 11326831
TI  - Tuberculin skin testing among BCG-vaccinated children who are household contacts.

PMID- 11326832
TI  - [Fracture toughness of cortical bone in tension, shear, and tear--a comparison of
      longitudinal and transverse fracture].
AB  - The fracture toughness at crack initiation was determined for bovine cortical
      bone under tension (mode I), shear (mode II), and tear (mode III). A total of 130
      compact tension specimens, compact shear specimens and triple pantleg specimens
      were used for the measurement of fracture toughness under tension, shear, and
      tear, respectively. Multiple-sample compliance method was utilized to measure the
      critical strain energy release rate (Gc) at the a/W = 0.55 (crack length, a, to
      specimen width, W, ratio). The critical stress intensity factor (Kc) was also
      calculated from the critical loading (PQ) of the specimens at the a/W = 0.55. The
      effect of the anisotropy of bone on its resistance to crack initiation under
      shear and tear loading was investigated as well. The fracture toughness of bone
      with precrack orientations parallel(designed as longitudinal fracture) to and
      that with precrack orientations normal (designed as transverse fracture) to the
      longitudinal axis of bone were compared. In longitudinal fracture, the critical
      strain energy release rates(Gc) of cortical bone under tension, shear, and tear
      were 644 +/- 102, 2430 +/- 836, and 1723 +/- 486 N/m, respectively. In transverse
      fracture, the critical strain energy release rates(Gc) of cortical bone under
      tesion, shear, and tear were 1374 +/- 183, 4710 +/- 1284, and 4016 +/- 948 N/m,
      respectively. An analysis of variance demonstrated that the crack initiation
      fracture toughness of bone under shear and tear loading is significantly greater
      than that under tensile loading in both longitudinal and transverse fracture. Our
      results also suggest that cortical bone has been "designed" to prevent crack
      initiation in transverse fracture under tension, shear, and tesar.

PMID- 11326833
TI  - [Research on power Doppler ultrasound imaging technique].
AB  - In this paper we introduce a method and an implementation of blood flow imaging
      by means of backscattered Doppler ultrasound power. Compared with Color Flow Map
      technique based on autocorrelation, this technique is relatively angle
      independent, aliasing free and more sensitive to blood flow signal with noise
      background. We present the theory, experimental system and in-vitro experimental
      results. The realization of this technique means a new stage of color Doppler
      ultrasound imaging technique in our country is coming.

PMID- 11326834
TI  - [Model-based study of time-dependent coronary blood flow distribution in left
      ventricular wall and its dependences on coronary pressure driving force].
AB  - The proposed model is of use for understanding the mechanism of intramyocardial
      circulation. There are three classical myocardial vascular nets in the model;
      each net has four vessel-size compartments which are characterized by time
      dependent nonlinear resistance and compliance. The experimentally measured timed
      varying perfusion and left ventricular pressure sources are used as driving
      inputs for the circulation. The phasic coronary blood flow characteristics
      predicted by the model exhibit waveform patterns that correlate qualitatively
      with the generally accepted results. In addition, more work is made about the
      myocardial infusion which is essentially controlled by the coronary pressure
      driving force. The results make it clear that the Intra-aortic balloon pumping
      and External counterpulsation are conducive to the balance between supply and
      demand of coronary blood flow.

PMID- 11326835
TI  - [Experimental study of distribution of stress and strain on pelvis in normal
      Chinese adult].
AB  - To approach the biomechanical properties of pelvis in normal Chinese adult, an
      intact pelvis taken from fresh healthy male cadaver after sudden death was used
      in this study. The pelvis joined up with lumber4, 5 and proximal segment of
      femurs. After appropriate management of the specimen, the loads in the simulated
      test (stand position of normal adult) are 300 N, 600 N and 900 N. With strain
      electric measuring apparatus, the distribution of stress and strain, and the
      actual linear strain of every measuring point are obtained. Data processing was
      performed on computer. The main stress sigma 1, sigma 2 and their direction
      angles were acquired. The results of the simulated test demonstrated that the
      stress of iliac bone adjacent to sacro-iliac articulation was maximum in all
      measuring points. The linear strain values of 0 degree direction parallel with
      coronal section were negative in majority, but those of 45 degrees and 90 degrees
      direction vertical with coronal section were positive in majority. So the
      distribution of the linear strain of pelvis should be very complicated. When 900
      N weight acted on the pelvis, the maximum main stress sigma max = 0.269-20.01 MPa
      and the minimum main stress sigma min = -0.095(-)-16.56 MPa. The angle of the
      maximum main stress with coronal section did not exceed 4 degrees.

PMID- 11326836
TI  - [Dual-energy separation imaging on an X-ray direct digital imaging system].
AB  - A method of dual-energy separation of bone and soft tissue images of chest based
      on an X-ray direct digital imaging system has been investigated. In this paper,
      the optimal thickness of the filter for high energy X-ray beam is discussed. An
      algorithm of correction of scattered radiation is employed before the separation
      algorithm. The separated images will be shown in the paper. The result shows that
      it is possible to use an ordinary broad spectral X-ray beam to acquire the dual
      energy images for routine X-ray diagnosis.

PMID- 11326837
TI  - [Myocardial cells action potential and contractive function in hemorrhagic shock
      in rabbits].
AB  - Anesthetized rabbits were subjected to a moderate degree of hemorrhagic shock.
      Lowering their mean arterial pressure to 5.3 KPa for 3 h, we measured the mean
      arterial pressure (MBP), left ventricular systolic pressure (LVSP), left
      ventricular maximum velocities of contraction (dp/dtmax), and myocardial
      electrical activity. The results of this study demonstrated that LVSP declined in
      parallel with MBP; that dp/dtmax dropped acutely on the instant of hemorrhagic
      shock; dp/dtmax went up by 48% on 15 min after shock; then dp/dtmax fell
      gradually, and by 3 h after shock the dp/dtmax values dropped to 20% of the
      baseline values; that intracellular sodium and potassium contents increased
      significantly in the hemorrhagic shocked rabbits; that myocardial resting
      potential (RP) and action potential amplitude (APH) diminished; and that action
      potential duration(APD), action potential repolarized 50% duration (APD 50), and
      repolarized 90% duration (APD 90) were markedly prolonged in the hemorrhagic
      shock, compared with control. The results suggested that in hemorrhagic shock
      myocardial cells fast sodium channel was closed while slow sodium and slow
      calcium channels, were opened; thus sodium and calcium infused and potassium
      exuded.

PMID- 11326838
TI  - [New digital carotid compressor].
AB  - Since 1979, many cases of paraganliomas in the neck have been successfully
      treated in Tianjin Cancer Hospital. All patients who would be subjected to this
      operation should undergo preoperative compressing exercises of the carotid artery
      to promote better circulation of collateral cerebral crossflow. Therefore, a
      reliable and compact instrument is necessary for the compressing exercises of the
      carotid artery and the long-term ambulatory monitoring of the compressing effect.
      This paper introduces our developed instrument, Adjustable and Digital Carotid
      compressor, which is based on the principle of volume-oscillometric method.
      During the gradual change in cuff pressure, the amplitude of consecutive arterial
      volume pulsation associated with pulse pressure shows change characteristically
      due to the nonlinearity of arterial pressure-volume (P-V) relation. Arterial
      pressure can be determined by detecting this change in the amplitude, while the
      arterial volume change can be noninvasively obtained as a function of this
      transmural pressure, provided that the state of blood flow are determined during
      this pressure measurement. Considering the simplicity and practicability of this
      instrument, we have designed a new portable one which consists of pulse pressure
      transducer, signal amplifier, peak voltage locking circuit and liquid crystal
      displayer. The validity and accuracy of this instrument and a few examples of its
      clinical application are presented.

PMID- 11326839
TI  - [R wave relative oscillometric blood pressure measurement].
AB  - To improve the accuracy of oscillometric blood pressure measurement, an artifact
      rejection method for oscillations detection called R wave-relative method was
      developed. It was mainly based on the correlation between ECG R wave and
      oscillation. Combining with identification of oscillation characteristics this
      method can distinguish valid signals from interference. This algorithm has been
      implemented in 8098 microcontroller. Its program flowchart has also been
      presented in this paper.

PMID- 11326840
TI  - [Effect of electric field on erythrocyte sedimentation rate. VI--dependence of
      electric field pattern].
AB  - An automatic analyzer of RBC rheological parameters and a microscopic
      morphological observation technique were employed to investigate the effect of
      three electric field patterns on erythrocyte sedimentation and aggregation in a
      physiological saline solution and in autologous plasma, respectively.
      Experimental results indicate that in a physiological saline solution: 1)
      Erythrocytes present a lightly aggregation and settle faster by an alternative
      current electric field; 2) There exists no erythrocyte aggregation by a direct
      current electric field of constant current and the enhancement of erythrocyte
      sedimentation is caused only by the action of electric force; 3) Time courses of
      erythrocyte sedimentation fit well with an exponential type curve by a direct
      current electric field of constant voltage, and this exponential type
      sedimentation curve is not caused by erythrocyte aggregation but caused by the
      decrease of circuit current with time duration. Also shown by experimental
      results is that the above three electric field patterns all affect the
      erythrocyte sedimentation in antologous plasma in different contents, which
      predicts some change in erythrocyte aggregation behavior in autologous plasma by
      an external electric field.

PMID- 11326841
TI  - [Water vapor permeability measurement of the materials used as a wound covering].
AB  - This paper introduces a new apparatus and method that suits to measuring the
      water vapor transmission rate (WVTR) of wound covering materials. WVTR of
      synthetic materials, amniotic membrane, porcine and cadaveric skin was measured
      under different conditions of four temperatures, three mediums, and "water cup"
      or "inverted water cup". The temperature was in close relationship with the WVTR
      except Omiderm, amniotic membrane, and cadaveric skin between 30 degrees C and 37
      degrees C groups. The medium did not affect the WVTR (P > 0.05). There was
      significant difference between the "water cup" and "inverted water cup" groups(P
      < 0.01). This study suggests that the apparatus is easy-to-operate, reliable and
      suitable for the measurement of WVTR of burn wound coverings and other membranous
      materials.

PMID- 11326842
TI  - [The preparation of poly (DL-lactide) hollow fiber and the release of drug in
      vitro].
AB  - The biodegradable hollow fibers of DL-PLA were prepared by a dry-wet phase
      inversion spinning process. By using four different spinning systems, DL-PLA
      hollow fibers with varying asymmetric membrane structure were obtained. The
      structure of hollow fiber wall was examined by SEM. In vitro release of
      norethisterone from the DL-PLA hollow fibers was also investigated. The hollow
      fibers were filled with a 50 wt% NET in castor oil. The DL-PLA hollow fibers NET
      release was found to be dependent on the membrane structure of the hollow fiber
      wall. Possible release mechanisms were discussed.

PMID- 11326843
TI  - [The development and clinical application of an easily carried Chinese
      electrocardiographic auto-diagnostic apparatus].
AB  - The 8090 single chip has been used as main core to complete the automatic
      process, such as controlling electrocardiographer, collecting information,
      measuring parameters, analysis, diagnosis, and printing Chinese report.

PMID- 11326844
TI  - [The developement of a new torque experiment device for biomaterials].
AB  - This paper introduces a biomaterial torque experiment apparatus which consists of
      AST486 computer, photodiode array, code device interface circuit, and
      magnetoelectric motional coil structure. According to experimental conditions,
      the computer sends out signal to the coil which under the magnetic field is
      activated to produce a series of desired torque and bring the sample to deflect.
      Angular displacement is measured by photodiode array and code device system. The
      whole system has good dynamics and high precision and could finish a series of
      torque experiment for biomaterials, and AST486 computer can automatically conduct
      signals analyzing and data processing.

PMID- 11326845
TI  - [A study on location of poles of terminal leads of ventricular fractionated
      potentials].
AB  - To eliminate the electromyogram-noise-signal from recording ventricular
      fractionated potentials (VFP) of the terminal leads(TLs), the multi-locations of
      leads were used to record ECG and VFP in 36 cases of controls and 68 cases of
      coronary heart disease. It was shown that the electromyogram-noise-signal could
      be minimized when TLs located separately at the point of infraclavicular cross
      lines axillaries media and the point of upperinguen cross lines axillaries media,
      and the essential formation of the ECG and VFP signals could not be changed
      except the QRS potentials becoming higher.

PMID- 11326846
TI  - [Preparation of liposomes of superoxide dismutase].
AB  - The liposomes of SOD were prepared by reverse-phase evaporation. By examining the
      important effects on preparation we obtained the liposomes of SOD. The
      encapsulation of SOD was more than 60%, and the stability of the liposomes was
      excellent.

PMID- 11326847
TI  - [Physical analysis on living tissues' thermal injury process].
AB  - In the light of solid mechanics as well as thermal physics, the physical factors
      causing thermal injury are correlated and a new thermomechanical model is
      established to quantitatively describe the injury process in living tissues under
      heat striking. The three-stage mode of thermal injury to living tissue is
      interpreted. The paper reflects our preliminary effort to further study this
      clinical phenomenon in point of micro mechanics and thermal science. It is of
      significance in revealing the mechanisms of subcutaneous bubble formation,
      development as well as tissue's thermal mechanical disruption.

PMID- 11326848
TI  - [Computer simulation of system controlling--application to designing of anti
      shock resuscitation therapy for burn injured patient].
AB  - The computer simulation of aim-controlling of changes in the circulative plasma
      volume, plasma protein concentration, hematocrit and electrolytes for five burn
      injured patients during their shock phase was carried out by using back
      propagation algorithm of the simulation system. Based on the aim-controlling, the
      better resuscitation therapy protocol for the patient was given by computer. The
      clinical application in five cases of the burns showed that the new method helped
      us to make individualized clinical anti-shock resuscitation formula for the burn
      injured patient more reasonable.

PMID- 11326849
TI  - [Experimental study on erythrocyte of obstructive jaundice patient: its changes
      of membrane protein and mechanical properties].
AB  - The component of the erythrocyte membrane protein under three states obstruction,
      after surgical relief of obstruction, and normal) were analyzed qualitatively by
      using SDS-PAGE and the method of thin scanning. The result revealed that the
      membrane protein band 4.2 was absent under the state of obstruction and it
      recovered after surgical relief of obstruction. Then the mechanical properties of
      the above three cases of erythrocytes were tested by the micropipette aspiration
      system and the data were analyzed by Voigt model. The result showed that the
      elastic modulus and the coefficient of viscosity of the erythrocytes under the
      state of obstruction were greater than those of the normal; thus the
      deformability decreased, but "overcorrection" appeared after surgical relief of
      obstruction. The possible relations between the mechanical properties and the
      change of membrane protein were discussed.

PMID- 11326850
TI  - [Dose distributions of linac-based radiosurgery for pineal region mass].
AB  - The doses of linac convergent-beam irradiations to pineal region were measured in
      an anthropomorphic phantom. The feasibility of a linac accelerator as a
      radiosurgery tool to treat small sized intracranial masses was evaluated. The
      influences of some irradiation parameters on the dose distributions were
      discussed. Linac-based radiosurgery can result in dose distributions similar to
      those achieved by gamma knife, so it is another safe and effective treatment
      technique of neurosurgery. The smaller the aperture is and the greater the
      irradiation arc travel is, the larger the dose gradient will be and the better
      the dose distribution will be. The maximum target doses are dependent greatly
      upon the collimater aperture. The appropriate irradiation arc travel and margin
      isodose were also discussed.

PMID- 11326851
TI  - [Application of analysis method of orthogonal polynomial regression to sports
      training].
AB  - During studying the dynamic changing rules of athlete's physiological workload in
      training by means of the polynomial regression method in recent years, we found:
      (1) If the number of the polynomial term or the order is relatively large (the
      order number M > 6), the equation's calculating amounts increase greatly and it
      is easy to have the phenomenon of accession to an "ill state" of the regression
      matrix or the matrix of the proper equation coefficients as well; (2) Both the
      accuracy for the fitted results and the stability decrease if there are strong
      correlation between the different terms in the polynomial (between the different
      odd power terms or even power terms). In order to overcome these defects we
      employed the orthogonal polynomial regression method and achieved a better
      effect.

PMID- 11326852
TI  - [Biocompatibility evaluation of Ti50Ni50-xCux shape memory alloys (I)--corrosion
      resistance].
AB  - By means of electrochemical methods, the corrosion resistance of Ti50Ni50 and
      Ti50Ni50-xCux (x = 1,2, 4,6,8) was investigated. It is discovered that
      repassivation potential of Ti50Ni50-xCux (x = 2,4,6,8) alloys is about 200 mV
      higher than that of Ti50Ni50 alloy. This means that the added Cu raises the
      repassivation of TiNi shape memory alloys and improves corrosion resistance.
      Pitting potentials of Ti50Ni50 and Ti50Ni50-xCux (x = 1,2,4,6,8) alloys increase
      with the rising solution pH value, but the repassivation potentials keep
      constant. The added Cu has no obvious influence on pitting potential (Epit) of
      TiNi alloys, meanwhile, the corrosion potential and corrosion rate of Ti50Ni50
      xCux (x = 1,2,4,6,8) alloys are irrelevant to its Cu content and the values are
      almost the same as that of TiNi alloys.

PMID- 11326853
TI  - [The flow of Casson fluid in flow chamber under all wall conditions].
AB  - The FEM analysis of Casson fluid flow in flow chamber under all wall conditions
      was made in this paper, and the result was compared with that of Newton and that
      of Casson fluid flow with plane hypothesis.

PMID- 11326854
TI  - [The effect of combining intra-aortic balloon pumping with tianma injection on
      myocardial ischemic-reperfusional injury in goats].
AB  - The objective of this study was to explore the effect of combined Intra-Aortic
      Balloon Pumping (I-ABP) and Tianma Injection on necrotic area in goat myocardial
      ischemic-reperfusional models which were established by two hours ischemia and a
      follow-up reperfusion. The results showed that the combined effect of IABP and
      Tianma Injection was more significant than that of IABP or Tianma separately. It
      is suggested that IABP and Tianma Injection have synergetic effect on the
      limitation of necrotic area, which possibly results from their mechanisms for
      decreasing the size of infarct.

PMID- 11326855
TI  - [The advances of research for cardiac contractile proteins structure and
      function].
AB  - Cardiac contractile proteins are the material basis of cardiac contractility.
      This paper introduces the Structures of two major cardiac contractile proteins:
      myosin and actin, especially the details of the two proteins' structure relevant
      to their function. At the same time, it describes the myosin and actin proteins'
      changes in normal and abnormal hearts so as to enrich our mind with knowledge of
      cardiac hypertrophy and heart failure at the molecular level.

PMID- 11326856
TI  - [Materials using in the prevention of scar formation after laminectomy].
AB  - The recurrent syndrome after laminectomy is related to the scar formation
      overlying epidural. To solve this catastrophic problem means to prevent the
      fibrosis. In the present review a variety of materials used in the inhibition or
      prevention of that syndrome are introduced, and their effects are reviewed and
      discussed. Some characteristics of the materials for prevention are summarized,
      and in our experiments the material point of view is rational.

PMID- 11326857
TI  - [Relationship between reference value (Wintrobe) of Chinese healthy female
      hematocrit and geographical factors].
AB  - To provide a basis for uniting the reference value standard (Wintrobe) of Chinese
      healthy female hematocrit, a study has been made on the relationship between the
      reference value of 22135 cases of Chinese female hematocrit and five geographical
      factors in China's 436 areas, which were determined by the method of Wintrobe. It
      is found that altitude is the main factor affecting the reference value
      (Wintrobe) of Chinese healthy female hematocrit. As the altitude increases
      gradually, the reference value (Wintrobe) of Chinese healthy female hematocrit
      also increases. For applying the method of mathematical regression analysis, a
      multivariate regression equation is formulated. In case geographical index values
      are obtained in an area, the reference value (Wintrobe) of Chinese healthy female
      heamtocrit for this area can be reckoned using the regression equation.
      Furthermore, according to the similarity of the reference values (Wintrobe) of
      Chinese healthy female hematocrit, China can be divided into six regions: Qinghai
      Xizang region, southwest region, northwest region, southeast region, north region
      and northeast region.

PMID- 11326858
TI  - Short-term results of using Lamellar Corneo-scleral patch graft for the Ahmed
      glaucoma valve implant surgery.
AB  - BACKGROUND: Human donor sclera is commonly used in glaucoma implant surgery to
      cover the external portiori of the silicone tube and prevent its erosion through
      the overlying conjunctiva. Corneo-scleral graft is used in this study as an
      alternative material for its desirable properties of being transparent, higher in
      tensile strength, cheap and more readily available. METHODS: Eighteen consecutive
      cases were implanted with the Ahmed glaucoma valve implant. The limbal portion of
      the silicone tube was covered by a corneo-scleral graft obtained from the corneo
      scleral rim left over following corneal transplant operation. The effectiveness
      in protecting the tube from erosion or migration, the transparency of the patch
      graft and complications encountered after surgery were assessed. RESULTS: At a
      mean follow-up of 6 months, all tubes were well protected and no complications
      related to the patch graft were encountered during intra and postoperative
      period. All corneo-scleral grafts remained transparent and healthy at the latest
      follow-up. CONCLUSION: Lamellar corneo-scleral tissue from residual corneal
      transplant material, with its many unique properties and advantages, appears to
      be a cheap, easily available and effective patch graft material for glaucoma
      implant surgery. Further explorations and studies on this material are
      recommended.

PMID- 11326859
TI  - Color Doppler imaging in the study of retrobulbar hemodynamic changes of primary
      angle-closure glaucoma.
AB  - PURPOSE: To investigate the hemodynamic changes of ophthalmic and central retinal
      artery (OA, CRA) in Primary Angle-closure Glaucoma (PACG) and the effects of
      intraocular pressure (IOP) on the retrobulbar hemodynamics. METHODS: The
      hemodynamic changes of OA, CRA in PACG were explored with color Doppler imaging
      (CDI) technique. Peak systolic blood flow velocity (PSV), end-diastolic blood
      flow velocity (EDV), pulsatile and resistive indices (PI, RI) were recorded and
      compared with those of the normal subjects. There were 20 patients (40 eyes) with
      PACG who were divided into two groups according to their IOP levels: ocular
      hypertension (15 eyes) and normal tension (25 eyes). RESULTS: Compared with the
      normal subjects, the hypertension group of PACG showed significant reduction in
      the EDV and increases in PI, RI of CRA; normal tension group of PACG also showed
      remarkable increase in RI of CRA. The ocular hypertension was significantly
      correlated with the RI and not with the EDV by the analysis of multiple linear
      regression (the partial correlation coefficient for IOP vs RI was 0.388, p =
      0.0234, for IOP vs EDV was 0.053, p = 0.7688). Compared with the normal group,
      there might be a trend of reduction in the EDV of the OA in PACG group.
      CONCLUSION: Intraocular pressure elevated is a major cause of the vascular
      resistance increased in PACG, which will make the end-diastolic blood flow of CRA
      decreased. There exists an abnormal vascular resistance in the normal tension
      eyes of PACG.

PMID- 11326860
TI  - Ultrasound biomicroscopic dark room provocative test.
AB  - PURPOSE: To compare the clinical application value of Ultrasound biomicrsocpic
      dark room provocative test with the traditional dark room test in screening
      primary angle closure glaucoma (PACG). METHODS: 22 eyes with PACG in prodromal
      stage and 30 eyes with deep anterior chamber and wide angle of 15 normal persons
      were observed in this trail. All 52 eyes were performed traditional dark room
      provocative test and ultrasound biomicorosopic darkroom test respectively. With
      different positive diagnostic criteria, the sensitivity of the two methods were
      compared using chi-squared analysis. RESULTS: After staying in the dark room for
      2 hours, In case group, IOP in 10 of 22 eyes rose more than 1.07 kPa (1kPa = 7.5
      mmHg), in 12 eyes less than 1.07 kPa or had no changes; appositional angle
      closure were found by Goldmann gonioscopy in 8 eyes: 3 eyes in two quadrants, 5
      eyes in more than two quadrants; the appositional angle closure was found by UBM
      in 15 eyes: 3 eyes in one quadrants, 5 eyes in two quadrants, 7 eyes in more than
      two quadrants. In the control group, IOP rose more than 1.07 kPa in 3 eyes. There
      were no appositional angle closure found in the control group. With the
      appositional angle closure as the positive diagnostic criteria, the sensitivity
      of the traditional darkroom test and UMB drak room test was 31.8% and 68.2%
      respectively. With chi-square test, there were statistically significant
      difference between the two methods (P < 0.05). CONCLUSION: The sensitivity of UBM
      dark room provocative test is higher than the traditional method. Dark room
      provocative test with UBM prompts the sensitivity and specificity of dark room
      test, reduces the false negative rate and false positive rate in screening PACG.
      It may help to reduce chances of misdiagnosis and missed diagnosis caused by
      traditional dark room test.

PMID- 11326861
TI  - Studies of primary angle closure glaucoma in China.
AB  - The recent researches on primary angle closure glaucoma (PACG) in China were
      reviewed. The prevalence of PACG (0.41%) in chinese is between the Caucasian and
      Eskimos, and chronic type is the dominant type in PACG. However, with the
      economic development and medical care improvements, the prevalence condition of
      PACG may change; several researches discovered that the mechanism of PACG,
      especially the chronic type, is not only because of pupil-blocking but also
      closely related to the mechanism of crowding of peripheral iris and the anterior
      location of the ciliary body. We supposed that PACG can be divided into several
      subtypes based on this mechnism. Also, we believe that the use of ultrasound
      biomicroscopy (UBM) and ophthalmic laser in China has promoted the research of
      PACG and improved the level of prevention and treatment of PACG.

PMID- 11326862
TI  - The characteristics of interaction between color and motion perception in primary
      open angle glaucoma.
AB  - PURPOSE: To investigate the characteristics of interaction between color and
      motion perception in primary open angle glaucoma (POAG) and measure motion
      perception of B, G and R cones, thus find a more sensitive method to diagnose the
      visual nerve damage in POAG. METHODS: Motion perceptions of B, G and R cones were
      isolated by blue, green and red vertical line stimulus displayed on the yellow,
      purple and blue background respectively, then measured the displacement threshold
      and flicking threshold of motion perception from each cones in POAG, and compared
      it with the age-match normals. RESULTS: The displacement threshold and flicking
      threshold of motion perception from B, G and R cones were all damaged in POAG
      compared with the normals, and the motion perception of G and B cones was
      deficits more obviously than the R cones. CONCLUSION: These findings support the
      suggestion that color provides an input to human motion perception. Magnocellular
      and parvocellular pathway may be significantly damaged in POAG, which indicates,
      that the combination of Motion Perception and color testing may reveal
      preclinical visual nerve damage in early POAG.

PMID- 11326863
TI  - The objective measure of color vision in primary open angle glaucoma.
AB  - PURPOSE: To objectively evaluate the clinical application of color pattern
      reversal visual evoked potential (CPR-VEP) on primary open angle glaucoma (POAG).
      METHODS: CPR-VEP and FM 100-hue test were performed in 31 eyes with POAG and 33
      normal eyes. Color pattern stimulation was presented by color monitor controlled
      by computer program. The reversal rate of the stimulating pattern was 2 Hz and
      the spatial frequency of the stimulating was 0.53 cycle/degree. The color
      stimulating pattern include White/Black, Red/Black, Green/Black, Blue/Black,
      Yellow/Black, Red/Green and Blue/Yellow. RESULTS: CPR-VEP P1 latencies were
      obviously prolonged in POAG group in comparison with normal control group in
      equiluminance. All CPR-VEP P1 amplitudes, except Blue/Black P1 amplitude, show no
      differences between POAG group and normal control group. CONCLUSION: P1 latencies
      of all CPR-VEP and P1 amplitude of Blue/Black CPR-VEP were parameters for
      identifying acquired dyschromatopsia caused by POAG. The results showed
      nonselective damages in color channels and luminance channel in POAG. CPR-VEP is
      helpful in detecting acquired dyschromatopsia.

PMID- 11326864
TI  - Observation of surface structure of retinoblastoma cell line.
AB  - OBJECTIVE: We study the adhesion molecules on the surface of SO-Rb50
      retinoblastoma cell line. METHODS: The distribution of proteoglycans in the
      retinoblastoma SO-Rb50 cell line was analyzed by histochem-electron microscopy,
      using Colloidal Iron in combination with a series of enzyme digestions. In
      addition, immunohistochemistry was performed using a panel of specific antibodies
      including neuron specific enolase (NSE), glial fibrillary acidic protein (GFAP),
      S-100 protein, fibronectin, laminin, and collagen IV. RESULTS:
      Immunohistochemical stains showed the most marked cytoplasmic reactivity of SO
      Rb50 cells with anti-NSE and anti-S100. The cells member and surface was postive
      with anti-NSE. No reactivity was noted with antibodies against laminin, GFAP, and
      collagen IV. After incubated with colloidal iron solution, three types of
      colloidal iron-positive stained material could be distinguished based on
      differences in shape, size, electron density: (1) electron dense particles, (2)
      the larger colloidal iron-positive filaments, (3) the smaller colloidal iron
      positive filaments, which were observed present on the tumor cells surface and in
      the extracellular matrix. CONCLUSION: We think that the cell surface
      proteoglycans is the main component of adhesion molecules of retinoblastoma,
      which may play a central role in mediating tumor cell adhesion to extracellular
      matrix and adjacent host cell.

PMID- 11326865
TI  - Cultivation and ultrastructural investigation of human iris pigment epithelial
      cells.
AB  - PURPOSE: To study the human iris pigment epithelial cells cultivation in vitro.
      METHODS: The iris pigment epithelial cells were isolated by scraping directly or
      by enzyme digestion and cultured in vitro. The cells were observed under the
      transmission electron microscope and analyzed by means of immunohistochemical
      assay. RESULTS: The cells obtained by scraping were easier to grow and to be
      passaged than those obtained by enzyme digestion. The primary cells appeared
      multigonal and arranged in monolayer. Abundant pigment granules were in the
      cytoplasm and diminished in succeeding generations. The maculae occludentes and
      desmosomes and microvilli which were characteristics of epithelial cells could be
      found under the electronmicroscope. The immunohistochemical assay showed positive
      reaction of keratin antigen in cultured cells. CONCLUSION: The human iris pigment
      epithelial cells could be cultured in vitro and the cells in primary generation
      some characteristics be preserved.

PMID- 11326866
TI  - Designing manufacturing and the clinic application of the prosthesis for the
      patients with large ocular defects.
AB  - PURPOSE: To design and manufacture the prosthesis of external type for patients
      with ocular large defects. METHODS: Silicon and polymethyl methacrylate (PMMA)
      were chosen the chief materials: The main procedures are: taking the impression,
      color mixture, making primitive form of the prosthesis, modification and
      fixation. RESULTS: Fifty patients with large ocular defects took the prosthesis,
      the cosmetic results are satisfactory. All the patients give satisfactory
      comments on the 5 main indexes: color 90%, stereo-feeling 100%, peripheral
      difference 86%, fidelity 98% and fixation 86%. CONCLUSIONS: To make ocular
      prosthesis, materials with good quality and complicated technology are needed.
      The prosthesis made by silicon combined with PMMA show good results. Among the
      procedures of making prosthesis, color mixture and fixation are the most
      important.

PMID- 11326867
TI  - The deterioration of refractive accommodative esotropia.
AB  - PURPOSE: To discuss the prevalence of deterioration and factors which may
      influence deterioration. METHODS: Records of 137 patients with the diagnosis of
      refractive accommodative esotropia who were followed for a period of at least 5
      years were reviewed. RESULTS: Twenty-three of the 137 patients (16.8%)
      deteriorated. Deterioration was most likely to occur in patients with a breakdown
      of the sensory status, or where anti-accommodative therapy was delayed. The age
      of onset, refractive status, and VA difference between two eyes were not
      etiologic factors in the process of deterioration. CONCLUSIONS: We think that
      early diagnosis of accommodative esotropia, timely prescription of optical
      correction and maintenance of binocularity play an important role in preventing
      deterioration from occurring.

PMID- 11326868
TI  - Variation of the multifocal visual evoked potential with eccentricity in
      isometropic amblyopes.
AB  - PURPOSE: To investigate the variation of visual function in different
      eccentricities of the visual field in isometropic amblyopes. METHOD: The stimulus
      matrix containing 61 hexagons was generated on a monitor. The diameter of the
      entire stimulating field was approximately 13.6 deg of arc; the frame rate of the
      monitor was 67 Hz. Every hexagon of the display contained a number of black and
      white small hexagonal patches which reversed during stimulation. These hexagons
      were simultaneously but independently modulated in time by the controlling
      computer program. The flashed elements were selected differently on each frame
      according to a computer-generated binary pseudo-random time series (m-sequence);
      the response contributions from each of the individual stimulus elements could be
      extracted from the cross corre-ation function. Subjects were asked to maintain
      fixation at the center of the stimulus pattern while each of the hexagons of the
      display reversed. The VERIS system extracted the local responses by cross
      correlating the input (binary m-sequence) and output (evoked response) signals.
      The latencies and amplitudes of the responses from the central 8.6 deg of arc in
      the visual field were analyzed. RESULT: Mean latency is about 22 ms longer at the
      fovea, and 10 ms longer in the first ring for the isometropic amblyopes than for
      the normal (control) subjects. The differences are highly significant at the
      fovea and in the first ring. In the second ring and the third ring, the
      difference have reduced to 3 to 4 ms. The latencies at the second ring and the
      third ring are not significantly different. In isometropic amblyopes, the P1-N2
      amplitude is about half of that in the normal subjects for the fovea and is
      similar to that for the normal subjects in the third ring. The P1-N2 amplitudes
      in the isometropic amblyopes are significant lower than the normal values from
      the center to the second ring. CONCLUSION: In isometropic amblyopia, the
      prolongation of latencies and the attenuation of the amplitudes of topographic
      VEPs are marked in the central region of the visual field and diminished in the
      periphery. The topographic VEP can objectively reflect the variation of visual
      response with eccentricity in the visual field.

PMID- 11326869
TI  - The strategy of prevention of blindness.
AB  - OBJECT: To reduce the prevalence of blindness at 0.30% by 2,000 in our country.
      METHODS: To realize the about goal effectively, the 4 aspects should be included.
      1. Epidemiological survey of ocular diseases. 2. Measures of prevention and
      treatment of blindness. 3. Establishment of a primary network for the prevention
      and treatment of ocular diseases. 4. Strengthening the organizations for
      prevention of ocular diseases. CONCLUSION: Restoration of eye sight can elevate
      people's health level, relieve the blind from sufferings and restore their work
      capacity. Launching a mass movement to prevent and treat blindness has
      significance in promoting both material and spiritual civilizations in our
      country.

PMID- 11326870
TI  - A model for blindness prevention.
AB  - OBJECTIVE: To introduce the work of the prevention and treatment of blindness of
      Zhongshan Ophthalmic Center, to find out the effective model of blindness
      prevention and treatment in China. METHOD: 1. To provide high quality clinical
      service to rural people. 2. To conduct epidemiological survey 3. To train local
      ophthalmic professionals 4. To promote international cooperation. RESULT: 40,000
      outpatients cases, 4,500 cataract surgeries have been accomplished. Thousands
      cataract blind have been rehabilitated. 9 papers concerning epidemiological
      survey have been published. After the international training courses, 50 local
      ophthalmic workers have been trained and 4 cataract surgery rehabilitation
      centers have been founded. CONCLUSION: An effective model for blindness
      prevention and treatment should be based on clinical service, population based
      epidemiological survey and local ophthalmic professionals training. International
      cooperation is also an important promoter.

PMID- 11326871
TI  - Comparative study of hyperacuity and retinometer tests for the evaluation of
      vision in patients with advanced cataract.
AB  - OBJECTIVE: To investigates the clinical application value of hyperacuity test for
      evaluating vision through dense cataracts. METHODS: Ten normal subjects (20
      years) were tested both with Bailey-Lovie type chart and three points vernier
      acuity test (one of the hyperacuity test); and retinometer test were performed
      preoperatively and postoperatively in 30 patients (31 eyes) with senile cataract.
      These patients' lens opacity was classified with LOCS III system. RESULTS: The
      correlation of vernier acuity and visual acuity of normal subjects is
      significant. The result of difference compression of pre-surgical and post
      surgical vernier acuity of 30 cataract patients is not significant. The
      correlation of retinometer findings with post-surgical visual acuity shows not
      statistically significant. Our result shows that there is good correlation
      between vernier acuity and post-surgical visual acuity. CONCLUSION: It appears
      that hyperacuity is a good test for foveal function behind dense cataract and
      other ocular opacities.

PMID- 11326872
TI  - [Chemotherapy of tuberculosis: current status and prospects].

PMID- 11326873
TI  - [Controlled clinical trial on efficacy of 5-month regimens and whole course
      intermittent 6-month regimens in treating bacillary pulmonary tuberculosis].
AB  - OBJECTIVE: To assess the therapeutic efficacy of rifapentine (L), to reduce the
      duration of treatment and the frequency of drug administration, and to observe
      the influence on efficacy and adverse reactions of using pyrazinamide (Z) through
      whole-course. METHOD: Two 5-month regimens respectively including rifampin (R)
      and L and two whole course intermittent regimens were designed as following: I:
      2SHRZ/3R2H2Z2; II: 2SHRZ/3L1H2Z2; III: 2S3H3R3Z3/4L1H2Z2; IV: 2S3H3R3Z3/4L1H2E2.
      A total of 366 newly-diagnosed bacillary pulmonary tuberculosis patients were
      admitted and randomly allocated. RESULTS: 339 cases completed the prescribed
      short course chemotherapy. The sputum conversion rates at the end of the
      treatment of groups I, II, III and IV were 97.0%, 94.1%, 100.0% and 97.2%
      respectively. X-ray resolution rates were 96.0%, 97.6%, 100.0% and 94.4%
      respectively. Cavity-close rates of the 5-month regimens and the 6-month regimens
      were 77% and 76%. Comparing the results among groups, there were no statistically
      significant differences (P > 0.05), and no obvious side-effect was found. 305
      patients have been followed up for 3 years since completion of the chemotherapy.
      The bacteriological relapse and bacteriological relapse with deterioration on
      chest X-ray in groups I, II, III and IV were seen in 2,3,6 and 3 cases
      respectively. CONCLUSION: Domestic-made rifapentine is a long-acting, highly
      effective antituberculosis drug. It is unnecessary to use Z in continuation
      phase, and it is possible to shorten the duration to 5 months with the
      appropriate combination of essential drugs, which is worthwhile for further
      study.

PMID- 11326874
TI  - [Polymerase chain reaction technique in monitoring treatment of bacillary
      pulmonary tuberculosis].
AB  - OBJECTIVE: To explore the relationship between sputum Mycobacterium tuberculosis
      as well as its DNA negative conversion and relapse in bacillary pulmonary
      tuberculosis during chemotherapy and 2 years after completion of treatment, and
      to evaluate the value of polymerase chain reaction (PCR) technique in monitoring
      the efficacy of treatment. METHOD: Eighty-seven patients with bacillary pulmonary
      tuberculosis were monthly examined by PCR technique, smear and culture methods,
      and were followed up for 2 years after treatment. RESULT: The duration of sputum
      negative conversion by PCR technique was 1-3 months later than that by smear and
      culture methods. The more the sputum bacteria, the longer the duration of PCR
      positive results. Positive PCR results maintained in 10 out of 87 patients for
      more than 1 year, among them 3 (30%) relapsed respectively at 8, 12 and 16 months
      after treatment. One PCR negative conversion case relapsed at 18 months after
      treatment. These 4 cases who regained sputum positive results and showed
      deterioration in chest X-ray films were admitted to hospital again. CONCLUSION:
      PCR technique is more practical than smear and culture methods in monitoring
      efficacy of the treatment of bacillary pulmonary tuberculosis, and is useful for
      evaluating cases with possible relapse.

PMID- 11326875
TI  - [CT images in differentiating tuberculous nodules from lung cancers with
      diameters less than 2 cm].
AB  - OBJECTIVE: To find out the CT characteristics of tuberculous nodules and lung
      cancers with diameters less than 2 cm, and to evaluate their value in
      differentiating the two diseases. METHOD: The CT images in thirty patients with
      tuberculous nodules and forty lung cancer patients with lesions less than 2 cm in
      diameter were compared. RESULTS: Smooth or clear edge, non-lobulation, small
      cavity, calcification, pleural thicking and adhesion, satellitic nidus and
      perifocal inflammation were found predominant in tuberculous nodules with short
      term dynamic changes in shapes, while shaggy border, shallow lobulation, vacuolus
      sign, air-bronchogram and typical pleural indentation were predominant in lung
      cancers without dynamic changes in shapes. CONCLUSION: Thin-slice CT scanning can
      provide useful images, which by short-term observations are important for
      differentiating these diseases.

PMID- 11326876
TI  - [Single-tube nested polymerase chain reaction technique in detecting
      Mycobacterium tuberculosis DNA].
AB  - OBJECTIVE: To study the sensitivity and specificity of single-tube nested
      polymerase chain reaction (SN-PCR) technique in detecting Mycobacterium
      tuberculosis DNA in paraffin-embedded tissues. METHOD: BCG DNA and the paraffin
      embedded tissues of 30 cases with typical tuberculous lymphadenitis were examined
      to detect the IS6110 specific insertion sequences DNA of Mycobacterium
      tuberculosis complex by general PCR(G-PCR), double-tube nested PCR (DN-PCR) and
      SN-PCR techniques. RESULT: Fifteen fg or more BCG DNA could show positive results
      by DN-PCR and SN-PCR techniques, while 480 fg by G-PCR method. The positive rates
      of G-PCR, DN-PCR, and SN-PCR in detecting Mycobacterium tuberculosis DNA in 30
      cases with tuberculous lymphadenitis were 43%, 100%, and 100% respectively, all
      of which were significantly different (P < 0.01) from that of the acid-fast
      staining method (10%). Significant differences in the positive rates also existed
      between G-PCR and DN-PCR, G-PCR and SN-PCR (both P < 0.01), while the positive
      rates of DN-PCR and SN-PCR were found same. CONCLUSION: The sensitivities of
      nested PCR techniques in detecting Mycobacterium tuberculosis are significantly
      higher than that of G-PCR, whereas the sensitivities as well as the specificities
      of SN-PCR and DN-PCR are the same. Thus SN-PCR seems more practicable.

PMID- 11326877
TI  - [Surgical treatment of tuberculous tracheobronchial stenosis].
AB  - OBJECTIVE: To report the experience of surgical treatment of tuberculous
      tracheobronchial stenosis. METHOD: Two trachial stenosis and 33 bronchial
      stenosis cases were analyzed. The modes of surgical treatment included:
      pneumonectomy in 14 cases, lobectomy in 13, lobectomy combined with bronchoplasty
      in 3, right pneumonectomy and partial trachial resection in 2, right main
      bronchus sleeve resection in 1, endotrachial granuloma resection in 1, right
      pneumonectomy and partial trachial resection combined with trachial
      reconstruction in 1. RESULT: There was no bronchopleural fistula,
      tracheobronchial restenosis and death due to operation. CONCLUSION: The first
      choice for the treatment of tuberculous tracheal or bronchial stenosis is
      lobectomy or pneumonectomy with trachial or bronchial plasty surgery.

PMID- 11326878
TI  - [The study of platelet function in patients with chronic pulmonary heart
      disease].
AB  - OBJECTIVE: To study the platelet function in patients with chronic pulmonary
      heart disease. METHOD: Subjects were divided into three groups (cor pulmonale
      exacerbation, cor pulmonale remission stage and normal control). Platelet
      adhesion rate (PAdT), platelet aggregation rate(PAgT), alpha-granule membrane
      protein (GMP-140) and glycoproteinII were measured by radioimmunoassay, flow
      cytometry and other methods. RESULT: In cor pulmonale exacerbation, the values of
      PAdT, PAgT, GMP-140 and GPII were31% +/- 16%, 14% +/- 8%, 190 +/- 49
      molecule/platelet and 145% +/- 36% respectively. In cor pulmonale remission
      stage, the values were 33% +/- 13%, 38% +/- 16%, 178 +/- 33 molecule/platelet and
      137% +/- 48% respectively. These findings showed that the values of PAdT, GMP-140
      and GPII in cor pulmonale exacerbation were markedly increased, whereas PAgT was
      significantly reduced. However, PAdT, PAgT, GMP-140 and GPII in remission stage
      were all higher than that of normal group. CONCLUSION: In vivo platelet
      activation is indeed present in patients with chronic pulmonary heart disease.

PMID- 11326879
TI  - [Relationship between plasma endothelin, nitric oxide, calcitonin gene-related
      peptide levels and pulmonary hemodynamics in patients with chronic cor
      pulmonale].
AB  - OBJECTIVE: To explore the relationship between plasma endothlin-1 (ET-1), nitric
      oxide (NO), calcitonin gene-related peptide (CGRP) levels and hypoxic pulmonary
      hypertension. METHOD: Cardiac catheterization was performed in 55 cases of
      chronic cor pulmonale to monitor the changes of their hemodynamic indices and to
      determine the levels of pulmonary arterial plasma ET-1, NO and CGRP. RESULT: The
      plasma ET-1 level of patients with pulmonary hypertension (Group A) was
      significantly higher than that of patients without pulmonary hypertension (Group
      B) and controls. The plasma NO level of group A was significantly lower than that
      of Group B and controls. The plasma CGRP level of ET-1 had a significantly
      negative correlation with PaO2 and positive correlation with pulmonary arterial
      pressure. The levels of NO and CGRP had significantly positive correlation with
      PaO2 and negative correlation with pulmonary arterial pressure. After 60-min
      oxygenation with 30% oxygen inhalation, the level of ET-1 decreased remarkably,
      but the levels of NO and CGRP went up notably. CONCLUSION: These results
      demonstrate that hypoxia affects plasma ET-1, NO, CGRP levels in patients with
      chronic cor pulmonale. ET-1, NO, CGRP play synergistic roles in regulation of
      pulmonary arterial pressure.

PMID- 11326880
TI  - [ICAM-1 and HLA-DR expression in bronchial epithelial cells from patients with
      chronic obstructive pulmonary disease].
AB  - OBJECTIVE: To study the expression of adhesion molecules in epithelial cells from
      patients with COPD. METHOD: The expression of ICAM-1 and HLA-DR in airway
      epithelial cells from 10 COPD patients, 7 asthmatic patients, 9 chronic
      bronchitis patients, and 10 healthy volunteers was evaluated using
      immunohistochemistry techniques. The cells were stained and analysed
      microscopically. RESULT: The percentage of neutrophils in brushing cells from
      COPD(0.04) were significantly higher than those from asthma(0.01) and normal
      subjects (0.01). More goblet cells were found in COPD (mean 0.13) and chronic
      bronchitis (mean 0.11) as compared with asthma (0.03) and healthy volunteers. As
      to the expression of ICAM-1 in COPD, the percentage of cells expressing ICAM
      1(15%) significantly increased in comparison with chronic bronchitis (6.28% P <
      0.05), healthy volunteer(1.8%, P < 0.05), and asthma (8.8%, P > 0.05). The score
      of expression of ICAM-1 in COPD was significantly higher than those in asthma (P
      < 0.05), chronic bronchitis (P < 0.05) and normal subjects (P < 0.001). As to the
      expression of HLA-DR in COPD, the percentage of cells expressing HLA-DR(5.9%)
      significantly increased in comparison with normal subjects (0.6% P < 0.05), but
      there was no significant difference among COPD, asthma and chronic bronchitis.
      The score of expression of HLA-DR in COPD was significantly higher than those in
      healthy volunteers (P < 0.001), chronic bronchitis (P < 0.001) and asthma (P <
      0.05). In addition, the percentage of neutrophils in brushing cells from COPD
      significantly correlated with the expression of ICAM-1 (r = 0.81, P < 0.01).
      CONCLUSION: Upregulation of ICAM-1 in epithelial cell from COPD correlates with
      the neutrophil infiltration in COPD. Lymphocytes are in an active state in COPD
      and the use of brush biopsies of the bronchial epithelium may serve as a
      diagnostic tool for differentiation among COPD, chronic bronchitis and asthma.

PMID- 11326881
TI  - [The inhibition effect of acute hypoxia on K+Ca-ATP channels of pulmonary artery
      smooth muscle cells of rats].
AB  - OBJECTIVE: To explore the possible mechanism underlying hypoxic pulmonary
      vasoconstriction, we evaluated the effect of acute hypoxia on potassium channels
      in pulmonary artery smooth muscle cells. METHOD: The single smooth muscle cell
      was freshly isolated from pulmonary artery (phi 700-200 microns) of Wistar rats
      with acute enzymatic digestion method. In symmetrical high K+ solution, we
      separated one outward K+ current from the patch of smooth muscle cells with
      inside-out configuration using patch-clamp technique. According to the
      electrophysiological response to the patch channel, this current was identified
      as the Ca2+, ATP activated potassium channel (K+Ca-ATP). The hypoxic solution was
      obtained by aeration with 5% CO2-balance N2 mixture. RESULT: The currents of K+Ca
      ATP in the patch of smooth muscle cells was much inhibited while the oxygen
      tension of solution was reduced from normoxic (PO2 > or = 13.33 kPa) to hypoxic
      (PO2 < or = 2.67 kPa) levels (P < 0.01). Cromakalim (10 nmol/L), an opener of
      potassium channel, could activate the currents of K+Ca-ATP decreased by acute
      hypoxia (P < 0.01). CONCLUSION: Acute hypoxia has an inhibition role on K+Ca-ATP
      currents in pulmonary artery smooth muscle cells, causes the membrane potentional
      depolarization, leads to pulmonary vasoconstriction, increases pulmonary vascular
      resistance and artery pressure. The decrease of K+Ca-ATP contributes to
      development of hypoxic pulmonary vasoconstriction. Cromakalim is one of effective
      antagonists for hypoxic pulmonary vasoconstriction.

PMID- 11326882
TI  - [Expression of surfactant protein SP-A, SP-B, and SP-C mRNA in lungs of rats with
      bleomycin-induced pulmonary fibrosis].
AB  - OBJECTIVE: The expressions of surfactant protein (SP)SP-A, SP-B, and SP-CmRNA in
      lungs of rats with bleomycin-induced pulmonary fibrosis were studied. METHOD: A
      single dose of bleomycin(BLM) was intratracheal injected to induce pulmonary
      fibrosis of rats. Animals were killed at day 3, 7, 14 and 28 after BLM
      administration. The total RNA was extracted from the lung tissue. The expressions
      of SPsmRNA were analyzed with Northern blot. RESULT: The number of alveolar type
      II epithelial cells increased in BLM-administered rats. The expressions of SP-A,
      SP-B and SP-CmRNA decreased at day 3 after BLM administration and decreased
      maximally at day 7, and then began to increase at day 14 and significantly
      increased at day 28, though they were still below the control levels. CONCLUSION:
      The results show that the changes of expressions of SP-A, SP-B and SP-CmRNA occur
      during the development of bleomycin-induced pulmonary fibrosis in rats and they
      may play a role in the pathogenesis of lung fibrosis.

PMID- 11326883
TI  - [The protective effect of removing circulatory TNF by immuno-adsorption on
      endotoxin-induced acute lung injury].
AB  - OBJECTIVE: To study the protective effect of removing circulatory TNF by
      immunoadsorption on endotoxin-induced acute lung injury in rabbits. METHOD: New
      Zealand white rabbits injected with lethal dose of endotoxin underwent
      hemoperfusion with immunoadsorbent. TNF and IL-8 levels in BALF were measured,
      the number of leukocytes and percentage of PMN in BALF were analyzed and the
      ratio of wet lung to body weight and pulmonary microvascular permeability index
      were also studied. In addition, the survival rate was observed. RESULT: Treatment
      with immunoadsorption markedly attenuated the pulmonary microvascular
      permeability increased by endotoxin and improved the survival rate. CONCLUSION:
      Immunoadsorption to remove circulating TNF is an effective way to protect rabbits
      against endotoxin-induced acute lung injury.

PMID- 11326884
TI  - [Advance in the study of tachykinin receptor in respiratory tract].

PMID- 11326885
TI  - [Complications and concomitant diseases of pulmonary tuberculosis].

PMID- 11326886
TI  - [Studies on mutation of rifampicin-resistant genes in M. tuberculosis].
AB  - OBJECTIVE: To understand mutation of rifampicin-resistant genes in M.
      tuberculosis clinical isolates, and to develop a new method for detecting drug
      resistance. METHOD: Analyzing the rpoB genes in 50 M. tuberculosis clinical
      isolates with polymerase chain reaction-single-stranded conformation polymorphism
      (PCR-SS-CP) and PCR-direct sequencing(PCR-DS) techniques. M. tuberculosis strain
      H37Rv was used as control. RESULT: Of 3 drug-sensitive isolates and 2 non
      rifampicin-resistant isolates selected, only 1 drug-sensitive isolate with
      abnormal rpoB SSCP profile had TCG-->TTG mutation at codon 531. Of 45 rifampicin
      resistant isolates, 35 isolates with abnormal SSCP profiles had mutations in rpoB
      sequences, in which 14 isolates displayed TCG-->TTG or TGG or TAC mutations at
      codon 531, 14 had CAC-->TAC or GAC or CCC or CTC or GTC mutations at codon 526, 2
      had GAC-->GTC or TAC mutations at codon 516, 2 had two point mutations, and 3 had
      different rpoB sequences from that of M. tuberculosis. CONCLUSION: Resistance to
      rifampicin in most M. tuberculosis isolates is due to the mutations on the genes
      encoding the RNA polymerase subunit (rpoB). PCR-SSCP and PCR-DS techniques might
      become simple, rapid and reliable diagnostic tests for rifampicin resistance in
      clinical isolates.

PMID- 11326887
TI  - [Clinical value of a rapid immunochromatographic assay in diagnosis and
      differential diagnosis of bone and joint tuberculosis].
AB  - OBJECTIVE: To evaluate the clinical value of a rapid immunochromatographic assay
      in diagnosis and differential diagnosis of bone and joint tuberculosis. METHOD:
      Antibodies in sera from 75 patients with active bone and joint tuberculosis, 69
      patients with non-tuberculous bone and joint diseases and 72 healthy individuals
      were detected by the rapid immunochromatographic assay using ICT-TB kit. RESULT:
      The positive rate was found to be 80% in the patients with active bone and joint
      tuberculosis, while 90% in the group with spinal tuberculosis, 53% in the extra
      spinal articular tuberculosis. The false positive rates were 4% and 3%
      respectively in those with other bone and joint diseases and healthy individuals.
      CONCLUSION: The assay is a rapid, sensitive and specific supplementary tool for
      the diagnosis of the bone and joint tuberculosis.

PMID- 11326888
TI  - [Effect of inhaled-corticosteroids on the mRNA expressions of endothelin-1 and
      endothelin converting enzyme in bronchial asthma].
AB  - OBJECTIVE: To investigate the expressions of endothelin-1(ET-1) and endothelin
      converting enzyme (ECE) mRNA in bronchial mucosal biopsis from asthmatics, and
      the effect of inhaled-corticosteroids on the expressions of ET-1 and ECE genes.
      METHOD: The expressions of ET-1 and ECEmRNA in bronchial mucosal tissue were
      evaluated by reverse transcription DNA polymerase chain reaction (RT-PCR); With
      fibro bronchoscopy, the naked-eye inflammatory severity and inflammatory score of
      bronchial mucoses were recorded. RESULT: (1) The expression level of ET-1 mRNA
      was 0.86 +/- 0.06 in non-steroids-treated group and 0.14 +/- 0.06 in control non
      asthmatic group. The expression of ECE mRNA in non-steroid group was 0.31 +/-
      0.04, and 0.30 +/- 0.05 in control group, P = 0.238. (2) The ET-1 and ECE mRNA
      expressions were 0.22 +/- 0.01 and 0.16 +/- 0.01 respectively in steroid treated
      group. (3) The naked-eye bronchial mucosal inflammatory score was 6.0 +/- 1.9 in
      non-steroids treated group, moreover, the expression of ET-1 mRNA was positively
      correlated with the score (r = 0.78, P < 0.05). CONCLUSION: There was markedly
      higher ET-1 mRNA expression in the bronchial mucosa in asthmatics, but the ECE
      mRNA expression was unchanged significantly; Inhaled corticosteroids obviously
      inhibited both ET-1 mRNA and ECE mRNA expressions in bronchial mucosa, which may
      be one of the anti-inflammatory mechanisms of inhaled-corticosteroid in
      management of bronchial asthma.

PMID- 11326889
TI  - [Studies on the role of colchicine in bleomycin-induced pulmonary fibrosis in
      rats].
AB  - OBJECTIVE: It has well been known that cytokines and extracellular matrix protein
      (ECM) have played an important role in pulmonary fibrosis in animal model as well
      as in patients. The purpose of this study was to evaluate the suppressive effect
      of colchicine (Colc.) in bleomycin (BLM)-treated rats. METHOD: Consecutive
      changes of interleukin-6(IL-6) and interleukin-8 (IL-8) released by alveolar
      macrophage (AM) were measured with murine B-cell hybridoma 7TD1 cells and micro
      membrane filter test. ECM and lipid peroxidation were observed with
      radioimmunoassay and biochemical assay respectively. RESULT: (1) Colc.
      significantly suppressed release of IL-6 by AM from day 7 to 28 (P < 0.05). But
      the level of IL-6 remained higher than that of the control. On the day 1 to 3, IL
      8 released by AM markedly decreased (P < 0.01) and the peak of IL-8 secretion had
      not appeared. (2) Colc. had no protective effects on AM lipid peroxidation
      injury. (3) Colc. markedly decreased the level of fibronectin (FN) by AM on day
      7, 14 (P < 0.01), as well as the level of laminin (LN) in bronchoalveolar lavage
      fluid (BALF) on day 7 to 28. However, the level of LN remained higher than that
      of control. (4) Colc. lessened the collagen deposition, and the lung
      hydroxyproline (HYP) content decreased on day 7, 14 and 28 (P < 0.05) compared
      with that of the control. (5) Colc. decreased exudation of inflammatory cells in
      the early response, as well as the degree of fibrosis in the late stage.
      CONCLUSION: Lipid peroxidation of AM might be one of the mechanisms of tissue
      injury and of AM activation, which increases the release of cytokines (IL-6, IL
      8) and deposition of extracellular matrix proteins (FN, LN). Colc. exertes
      somewhat inhibitory effects on the process of pulmonary fibrosis in animal model.
      Factors other than AM and its cytokines might also be involved in the
      pathogenesis of pulmonary fibrosis in experimental rats.

PMID- 11326890
TI  - [Change of pulmonary diffusing capacity, membrane diffusing capacity and
      pulmonary capillary blood volume in patients with COPD and connective tissue
      disease at rest and post-exercise].
AB  - OBJECTIVE: Studying the changes of pulmonary diffusing capacity (DL), alveolar
      capillary membrane diffusing capacity (Dm) and pulmonary capillary blood volume
      (Vc) in patients with COPD and connective tissue disease (CTD) at rest and post
      exercise; evaluating the diagnostic values of DL, Dm and Vc in early stage of
      pulmonary involvement of CTD. METHOD: Spirometry was performed in the sit
      position. Several measurements of diffusing capacity of the lung for carbon
      monoxide (DLCO) were measured by single-breath method at increasing alveolar
      oxygen tension. The estimations of Dm and Vc were done by the method of Roughton
      and Forster. RESULT: (1) In COPD group, the values of DL were lower than that of
      the control group at rest. The decreases were due to the reduction of Dm, but Vc
      were normal. In CTD group, all the value of DL, Dm and Vc were lower than that of
      its control group at rest. (2) COPD patients had the higher DL, Dm and Vc after
      the end of exercise than that of at rest. But the changes of DL Dm and Vc in COPD
      patients were lower compared with the control group. In contrast to the control
      group, DL, Dm and Vc did not increase or even decreased after the end of exercise
      in CTD group. (3) There was no significant differences of DL, Dm and Vc between
      the 7 CTD patients with normal pulmonary volume and DLCO and the control subjects
      at rest. But after the end of exercise, DL, Dm and Vc of CTD patients kept
      unchanging or even decreasing. The difference between CTD patients and its
      control group was found significant. CONCLUSION: The measurements of post
      exercise Dm and Vc are sensitive tests for pulmonary involvement in of CTD
      patients. The results are abmormal much earlier in subject with minimal dyspnea
      and roentgenologic change. They are useful tests for early stage CTD.

PMID- 11326891
TI  - [Generation and prediction of hypoxemia in patients with chronic obstructive
      pulmonary disease].
AB  - OBJECTIVE: To study the pathogenesis of nocturnal hypoxemia in patients with
      chronic obstructive pulmonary disease (COPD). METHOD: Daytime pulmonary
      functions, arterial blood gases and nocturnal oxygen level were measured in 30
      patients and compared with those of 8 normal subjects. RESULTS: The nocturnal
      oxygen level significantly decreased in patients with COPD compared with that in
      normal subjects, especially during rapid eye movement (REM) period. The decreased
      extents of nocturnal mean oxyhemoglobin saturation (MSaO2) and nocturnal minimum
      oxyhemoglobin saturation (MmSaO2) were also very high in COPD (P < 0.05). From
      the distribution of oxyhemoglobin, the percentage of the time that oxyhemoglobin
      saturation (SaO2) < 80% and < 90% during sleep (T80, T90) in patients were found
      higher than those in normal subjects (P < 0.05). The sleep time in which SaO2
      below 90 percent obviously increased in COPD patients. The correlative analysis
      indicated that daytime SaO2 and FEV1% were related to the nocturnal mean
      oxyhemoglobin saturation (r = 0.79, 0.54). So predictive formula of nocturnal
      oxyhemoglobin level was derived as follows: MSaO2(%) = 1.03 x SaO2(%) + 0.19 x
      FEV1%(%) - 14.35(r = 0.83). Daytime SaO2 and PaCO2 were also found concerned with
      nocturnal oxygen distribution: T80(%) = -2.64 x SaO2(%) + 6.98 x PaCO2(kPa) +
      211.31(r = 0.78), T90(%) = -4.49 x SaO2(%) + 437.18(r = 0.62). CONCLUSION: It was
      observered that hypoxemia became worse in patients with COPD than in normal
      subjects during sleep. The level and the distribution of nocturnal oxygen could
      be predicted by daytime SaO2 and PaCO2. All these indicated that nocturnal oxygen
      therapy could be useful to improve the outcome of the COPD patients.

PMID- 11326892
TI  - [Radical neck dissection in treating cervical lymph node tuberculosis].
AB  - OBJECTIVE: To evaluate the significance of radical neck dissection in treatment
      of mixed-type cervical lymph node tuberculosis. METHOD: One hundred twenty-two
      cases with mixed-type cervical lymph node tuberculosis were treated with radical
      neck dissection and the results of the treatment were reported. The size, number,
      location and pathologic types of abscess, fistula and lymph node were also
      analyzed. RESULT: All the patients were cured without relapse during 1-7 year
      follow-up. Spreading antegrade infection and chronic recurrence were found to be
      the characteristics of mixed-type cervical lymph node tuberculosis. CONCLUSION:
      Radical neck dissection is an effective and safe approach for treating the
      disease.

PMID- 11326893
TI  - [Protecting infection by using rhG-CSF in patients with lung cancer during
      chemotherapeutic courses].
AB  - OBJECTIVE: To recognize the prophylactic effect of rhG-CSF used on infection
      complications secondary to chemotherapy in patients with lung cancer. METHOD: The
      infection complications and the neutropenia secondary to chemotherapy in 163
      cases of lung cancer patients with or without rhG-CSF were retrospectively
      analyzed. RESULT: Rhg-CSF administration reduced the frequency of infection
      complications, and there was a significant difference(P < 0.005) in the frequency
      of infection between the G-CSF group's patients (infections incidence 25%) and
      non-G-CSF group's (56%). The incidence of neutropenia in G-CSF group' patients is
      obviously less than that in non-G-CSF group's (P < 0.005). The median number of
      days of the neutropenia (neutrophil count of < 1.0 x 10(9) in G-CSF group(3 days)
      is less than that in non-G-CSF group(4 days)(P < 0.001). However, there was no
      significant difference (P > 0.05) between G-CSF group(63%) and non-G-CSF
      group(76%) in terms of response of the infection complications. CONCLUSION: Our
      data has shown that the administration of rhG-CSF as an adjunct to chemotherapy
      in patients with lung cancer can accelerate neutrophil recovery and shorten the
      duration of neutropenia, and lead to reductions in the incidence of infection
      complications, and also has the potential to increase the amount of cytotoxic
      chemotherapy and the quantity of life.

PMID- 11326894
TI  - [Effects of an extract of salviae miltiorrhizae (764-3) on structural remodeling
      of intra-acinar pulmonary artery in pulmonary hypertension due to chronic hypoxia
      and monocrotaline in rats].
AB  - OBJECTIVE: To investigate the effects of an extract of salviae miltiorrhizae (764
      3) on the percentage of intra-acinar muscular artery (MA), partal MA(PMA) and
      nonmuscular MA(NMA) and collagen deposition in the media of MA in rats with
      hypoxia and MCT-induced pulmonary hypertension. METHOD: Wistar rats were divided
      into 12 groups. The hypobaric hypoxic 51 kPa (1 kPa = 7.5 mmHg) and MCT (60 mg/kg
      intraperitoneal injection) rats were treated with 764-3 (20 mg/kg), beta
      aminopropionitrile (BAPN, 150 mg/kg) and 764-3 (40 mg/kg), respectively. At each
      time point, the hemodynamic and morphological parameters were measured. RESULT:
      After hypoxia for 2 weeks, the percentage of MA increased (P < 0.001), of NMA
      decreased (P < 0.001) and of PMA no obvious change; and after 4 weeks, the above
      changes became to be more striking and the collagen content in the media of MA
      increased (P < 0.001). The MCT-treated rats had more severe changes than the
      hypoxic rats. Both 764-3 and BAPN could inhibit the changes, decreased the
      collagen content and BAPN was more effective than 764-3(P < 0.05). CONCLUSION:
      764-3 can partially inhibit collagen deposition in pulmonary arterioles attenuate
      hypoxia and MCT-induced pulmonary hypertension, reduce the percentage of MA, and
      has a moderate influence on collagen deposition as compared with BAPN.

PMID- 11326895
TI  - [Radiological imaging in diagnosis for atypical pulmonary abscess].
AB  - OBJECTIVE: Evaluate characteristics of the radiological image of atypical
      pulmonary abscess. METHOD: The X-ray and CT image in 30 cases with atypical
      pulmonary abscess were analyzed. RESULT: The atypical pulmonary abscesses were
      classified into solitary ball type and irregular infiltration type. And these two
      types showed the following characteristics: circumscribed dissolution or small
      cavity; local congestion sign; coarse and long funiform shadow in margin; ambient
      circumscribed infiltrating shadow; adjacent pleural thickening and adhesion.
      CONCLUSION: Existence of abscess and perifocal inflammatory changes is the key to
      diagnose and differentiate this atypical variant of lung abscess.

PMID- 11326896
TI  - [Relationship between left cardiac function and oxygen transport of cor pulmonale
      during acute attack at high altitude].
AB  - OBJECTIVE: Relationship between left cardiac function and oxygen transport in the
      patients with cor pulmonale during acute attack at high altitude was studied to
      benefit prevention and treatment of cor pulmonale. METHOD: 20 cases were divided
      into 16 as a surviving group and 4 as a death group. CO was determined by Swan
      Ganz catheter from internal carotid vein to pulmonary artery directly. RESULT:
      (1) CI in the patients decreased (2.9 +/- 0.4 L.min-1.m-2). mPAP (4.9 +/- 1.3
      kPa) and PAWP (1.5 +/- 0.8 kPa) increased. LVSWI (35 +/- 11 g.cm-1.min-1)
      dropped. (2) above Indicies in surviving group improved after comprehensive
      treatment. CI and LVSWI increased. But LVSWI in death group continued to decline.
      mPAP and PAWP were not changed; (3) There was significant corelation between
      LVSVI and DO2(r = 0.4318, P < 0.05). CONCLUSION: LVSWI of cor pulmonale could
      affect DO2 level directly and closely relate to prognosis.

PMID- 11326897
TI  - [Nervous system damage in patients with sarcoidosis].
AB  - OBJECTIVE: For the purpose to evaluate the clinical characteristics of nervous
      involvement in sarcoidosis patients, and to improve the diagnostic skills.
      METHOD: 92 cases with sarcoidosis were reviewed, and 5 of them with damages to
      nervous system were retrospectively analyzed. RESULT: One of the 92 cases was
      proved to be brain sarcoidosis by autopsy, and 4 presented damages to meninges,
      cranial, spinal and peripheral nerves. The clinical manifestations of the above 5
      cases included epilepsy, intracranial hypertension, motor weakness, facial
      paralysis and dysopia. CONCLUSION: Clinical manifestations of patients with
      sarcoidosis of the nervous system are varied. Sarcoidosis may be one of the
      potential causes of some unproven abnormalities in brain, spinal cord, cranial
      and peripheral nerves.

PMID- 11326898
TI  - [Molecular biology of KatG gene and isoniazid resistence in Mycobacterium
      tuberculosis].

PMID- 11326900
TI  - [Human lens epithelial cells culture in vitro].
AB  - PURPOSE: To provide a simple and rapid procedure to culture human len epithelial
      cells in vitro. METHODS: Specimens of capsule lentils were isolated from lens by
      microscissors. They were cut into small segments and then directly implanted into
      basks(culture bottles). The tissue pieces were cultured in a incubation at 37
      degrees C with PR1640 until attached cells reached confluence. The len epithelium
      were passaged by tropism. RESULTS: Len epithelial cells usually appeared after 4
      days in incubation. The cells growed rapidly in a way of attachments. CONCLUSION:
      Len epithelial cells were easily cultured with our method. The procedure is
      simple, rapid and highly successful.

PMID- 11326899
TI  - [Study of antiproliferative effect of gamma-interferon and heparin on rabbit lens
      epithelial cell (RLEC) cultured in vitro].
AB  - PURPOSE: To study the antiproliferative effect of gamma-interferon and heparin on
      rabbit lens epithelial cell(RLEC). METHODS: First passage RLEC was obtained from
      healthy New zealand white rabbits. Third passage cells were incubated with gamma
      interferon with concentration from 0.1 u/ml to 10,000 u/ml and heparin with
      concentration from 100-5,000 u/ml for 48 hours. The Mosmann's MTT colorimeltric
      assay was used to quantitate the RLEC proliferative activation. RESULTS: In lower
      concentration groups (0.1-100 u/ml), gamma-interferon had no antiproliferative
      effect on RLEC, while in higher concentration groups (1,000 u/ml-10,000 u/ml) it
      exhibited some antiproliferative effect on RLEC, the rate of inhibition were 27%
      and 38%, respectively. Heparin of all experimental groups had antiproliferative
      effect on RLEC. CONCLUSION: gamma-interferon and heparin with certain
      concentration can inhibit proliferation of RLEC directly.

PMID- 11326901
TI  - [Study of the antioxidative effect of tea polyphenol and allitridi on cultured
      rat lens in vitro].
AB  - PURPOSE: To investigate the oxidative modification of lens proteins in the
      presence of H2O2 in vitro and the protective effect of tea polyphenol(TP) and
      allitridi. METHODS: Rat lenses were cultured in DMEM medium containing H2O2(1mM)
      at 37 degrees C in CO2 incubator. Iron and copper salts were added to the medium.
      At 24 or 48 hours, photographs were recorded the changes in transparency of rat
      lens and lens proteins were analysed by SDS-PAGE and IEF. TP and allitridi were
      added to the medium with lens in order to test the antioxidant effects. RESULTS:
      Lens opacities occurred at the equatorial region by 24 hours, progressing to
      totally opaque by 48 hours. SDS-PAGE revealed new bands higher than 43KD were
      found. In addition the 30KD band disappeared in medium containing copper salt.
      With addition of TP or allitridi to the culture system, all lens remained
      transparent. CONCLUSION: Exposure rat lens to H2O2 with iron or copper salt
      resulted in opacification of lens with crosslinking of crystallins and
      degradation of lens polypeptides. Addition of TP or allitridi prevented the lens
      from oxidative stress.

PMID- 11326902
TI  - [Pediatric ocular trauma: a retrospective survey].
AB  - PURPOSE: To determine the risk factors for pediatric ocular injuries, especially
      those resulting in severe visual impairment, and to identify the trends and
      preventable causes. METHODS: A retrospective survey was conducted for all
      pediatric trauma cases at Zhongshan Ophthalmic Center from January 1989 through
      December 1992. Four hundred eighty-seven cases of 15 years old or younger were
      recruited in this study. Stepwise regression analysis was used to identify the
      relations between the visual prognosis and the potential risk factors (age,
      gender, time after injury, type of injury, and cause of injury) RESULTS: The male
      to female ratio was approximately 3:1, and most were 4 to 8 years old. Non-
      perforating trauma in the anterior segment was the most common type of injury.
      The final recorded best corrected visual acuity was 0.3 or better in 65% of the
      patients, while 19% were found to be 0.05 or worse with best correction. The
      following formula was generated by multiple linear regression model: Visual
      outcome = 0.963775 - 0.0896543 x (type of injury). CONCLUSION: Pediatric ocular
      trauma may cause severe visual impairment and occurs most frequently at the age
      of 4 to 8 years. The visual outcome is mainly associated with the type of injury.

PMID- 11326903
TI  - [Effect of levodopa on visual evoked potential in amblyopia].
AB  - PURPOSE: To evaluate the efficacy of levodpa treatment for amblyopia. METHODS:
      The patients with amblyopin were given a single dose of levodopa, and the normal
      control group was established with the other normal eye in unilateral amblyopia.
      Their pattern visual evoked potential(PVEP) were tested before and after taking
      levodopa. RESULTS: After taking a single dose of levodopa, the PVEP in the normal
      eyes showed that the N1P1 amplitudes evoked by middle spatial frequency stimuli
      and the P1N2 amplitudes evoked by high spatial frequency stimuli increased,
      however, in the amblyopic eyes showed that the N1 latency evoked by low spatial
      frequency stimuli and P1 latency evoked by middle spatial frequency decreased.
      CONCLUSION: A single dose of levodopa administration can induce improvement of
      PVEP in the amblyopic eyes, and levodopa may be efficacious in the amblyopic
      therapy.

PMID- 11326904
TI  - [The objective evaluation of the interaction between color vision and motion
      perception].
AB  - PURPOSE: To measure equiluminance values of green/red grating luminosity ratios
      with different moving velocity in normal subjects and to explore the interaction
      between color vision and motion perception. METHODS: Optokinetic nystagmus (OKN)
      of eye movement elicited by moving color grating stimulus could be recorded with
      electrooculograph (EOG). The equiluminance points were determined when OKN
      changed in direction in various moving velocities. Sixteen cases (32 eyes) normal
      subjects were tested, 6 cases male and 10 cases female, Age ranged from 20 to 51
      years old. RESULTS: The mean equiluminance points were 0.525, 0.425, 0.397,
      0.391, 0.367 under 595, 400, 301, 239 and 200 mm/s groups of grating moving
      velocity respectively. There were statistically significant differences of mean
      equiluminance points among 595 mm/s group and other groups (P < 0.01), there were
      no statistically significant differences of mean equiluminance points among other
      4 groups (P > 0.05). CONCLUSION: There are some influences to color vision under
      the high moving condition.

PMID- 11326905
TI  - [The primary study of ultrasound biomicroscope in imaging anterior segment tumors
      of eye].
AB  - PURPOSE: To evaluate the use of ultrasound biomicroscope (UBM) in imaging
      anterior segment tumors of eye. METHODS: 13 cases of anterior segment tumors of
      eye were examined with UBM. RESULTS: 3 cases had the ocular history of trauma or
      surgery and were clinically diagnosed as anterior iris cysts. UBM displayed the
      cysts as thin-walled, no internal reflectivity, and at the locate of anterior
      humour angle; 8 cases had superficial anterior humour, narrow anterior angle and
      clinically be suspected as tumors behind iris or ciliary body. UBM showed cystic
      reflectivity in 7 cases and a solid tumor in ciliary body in one case. 2 cases
      were clinically diagnosed as iris nevi. UBM displayed solid convex lesions.
      CONCLUSION: UBM is a valuable new technique in the diagnosis and accurate
      localization of anterior segment tumors.

PMID- 11326906
TI  - [Application of ultrasound biomicroscopy in diagnosis of anterior segment
      vitreoretinal disorders].
AB  - PURPOSE: To investigate the diagnostic value of ultrasound biomicroscopy(UBM) in
      anterior segment vitreoretinal disorders(ASVD). METHODS: 60 eyes of 58 sequential
      patients were examined with UBM. The ultrasound biomicroscopic images were
      compared with the results of clinic examination, B-scan ultrasonography and the
      finding during surgery to evaluate the reliability of UBM for ASVD. RESULTS: UBM
      allows structural details of the conjunctiva, rectus muscle, sclera, uvea, retina
      and vitreous to be visualized at microscopic resolution in living eye. The area
      of UBM may cover from cornea to vitreous base, partially to the equator of eye. A
      variety of the changes of ASVD were imaged in 60 eyes, including retinal
      detachment in 43 eyes, retinal circumferential contraction in 29 eyes, retinal
      anterior displacement in 24 eyes, vitreous opacities or fibrosis in 57 eyes,
      ciliary orchoroidal detachment in 26 eyes, ciliary nonpigmented epithelial
      detachment in 6 eyes, proliferative tissue at the sclerotomy site in 9 eyes,
      retinal neoplasm in 2 eyes, ciliary cyst in 6 eyes, proliferation of peripheral
      silicone oil in 8 eyes, silicone oil emulsification in 7 eyes and vitreous
      foreign body in 2 eyes, respectively. CONCLUSIONS: Our studies showed the
      feasibility of UBM for ASVD not visible by current techniques UBM can be used for
      the diagnosis, differential diagnosis and the instructive treatments of ASVD.

PMID- 11326907
TI  - [Research advances in genes associated with glaucoma].

PMID- 11326908
TI  - [Cost-effectiveness analysis of the screening strategies for primary angle
      closure glaucoma].
AB  - PURPOSE: To evaluate varlous primary angle clouse glaucoma(PACG)screening
      strategies by cost effectiveness analysis for choosing the best screening
      strategy. METHODS: We designed a model of the process of PACG screening,
      diagnosis, treatment, and estimated variable parameters of this model through
      literatures reviewed and the results of our study. Then four screening
      strategiers which are oblique flashlight test, measurement of axial anterior
      chamber depth (AACD), examination of peripheral anterior chamber depth (PACD),
      and combination of oblique flashlight test with examination of PACD in series
      were calculated by computer to obtain the costs for various screening strategies
      and the quality ajusted life years (QALYs) saved. We performed sensitivity
      analysis to determine how the variation in the parameter assumptions would affect
      the calculated cost effectiveness of the various screening strategies. Based on
      the principle of cost effectiveness, the screening strategy of more cost
      effective would be chosen. RESULTS: The results showed that no matter what age
      group, the screening strategy of oblique flashlight test and measuring PACD
      combined in series is the lowest cost per QALY gained than other strategies. This
      screening strategy is optimum, next is oblique flashlight test Screening method.
      We found that screening strategies not only gains QALY, but also is cost saving
      as well in the range 40-< 70 years old. sensitivity analysis result showed that
      optimum strategy is still the combined serial strategy, in addition to the
      capable closure angle ratio of a population with a 10% up and down, the oblique
      flashlight test became an optimum strategy and the combined serial method became
      next in > or = 70 years old group. CONCLUSION: The results showed that the
      oblique flashlight test and measurement of PACD combined in series is an optimum
      screening strategy. This research suggests that using adequate screening strategy
      should not only increase the QALYs, but also save the cost for the government and
      the patients themselves.

PMID- 11326909
TI  - [Diplopia after intraocular lens implantation].
AB  - PURPOSE: Seven patients with diplopia after intraocular lens implantation were
      reported. Possible causes and prevention of diplopia were investigated
      preliminarily. METHODS: Sixty successive cases, who had accepted uniocular
      cataract extraction and intraocular lens implantation, were followed-up. The
      kinds of diplopia, position of eyes, the movements of eyes, refrective state,
      pupil, fundus of eyes and the states of IOL were examined in all diplopia cases.
      RESULTS: The incidence of diplopia in our cases was 11.67%. There was a close
      relationship between postoperative diplopia and preexistent strabismus, fusion
      disruption, myotoxic effects of local anesthetics, decentration of intraocular
      lens, macular disease and in identical opacity of posterior capsule. CONCLUSION:
      Diplopia is a important complication after cataract extraction and intraocular
      lens implantation. Usually, it is difficult to deal with. It is helpful for
      decreasing diplopia to take corresponding methods according to possible causes.

PMID- 11326910
TI  - [The combined procedure of limbal transplantation (LT) and penetrating
      keratoplasty (PK) for severe ocular obsolete chemical or thermal burns].
AB  - PURPOSE: To improve the prognosis of grafts for obsolete ocular chemical or
      thermal burns. METHODS: LT + PK or PK were performed in 28 eyes with severe
      chemical or thermal burns. The effects of the two groups were compared. RESULTS:
      In LT + PK group(12 eyes), during 5 to 28 months of follow-up, the results showed
      improved visual acuity in 9 eyes (75%), maintained stable epithelial adhesion
      without recurrent erosion or persistent epithelial defect in 11 eyes (91.67%),
      graft transparent in 9 eyes (75%). Nine eyes (75%) showed prevented
      neovascularization and conjunctival tissue from growing into graft. Allograft
      rejection were identified in 4 eyes (33.33%). In routine PK group (16 eyes),
      during 3 to 22 months of follow-up, the results showed improved visual acuity in
      4 eyes (25%), maintained stable epithelial adhesion without recurrent erosion or
      PCED in 8 eyes (50%), graft transparent in 4 eyes (25%). Four eyes (25%) showed
      prevented neovascularization and conjunctival tissue from growing into cornea.
      CONCLUSIONS: Combined procedure of LT and PK is an effective treatment for severe
      ocular chemical or thermal burns. It can reduce persistent corneal epithelial
      defect and prevent neovascularization and conjunctival epithelial from growing
      into cornea thus maintaining graft transparent and improving visual acuity.

PMID- 11326911
TI  - [A clinicopathological analysis of keratoacanthoma in eye].
AB  - PURPOSE: To discuss clinic and histopathologic features of keratoacanthoma. The
      diagnosis and differential diagnosis were discussed. METHODS: The authors analyze
      clinical characteristics of keratoacanthoma which is testified by hisopathology.
      Clinically, the tumors developed rapidly. They appeared as a dome or nodule with
      a central keratin filled crater and elevated rolled margins. RESULTS:
      Histologically, they had a cup-differentiated squamous opithalium surrounding a
      central mass of keratin. The base was rather uniform. The lesions may extend into
      underlying stroma even orbicularis muscle. CONCLUSION: Keratoacanthoma is a
      specialized variant of pseudocarcinomatous hyperplasia. It has clinic and
      histopathologic characteristics and differs from other tumors.

PMID- 11326913
TI  - [Importance of scientific research design to improve the quality of clinical
      study].

PMID- 11326912
TI  - [The oculocardiac reflexes in extraocular muscle operations of generally
      anesthetized children].

PMID- 11326915
TI  - [Investigation of erythrocyte immune function of patients with endometriosis].
AB  - OBJECTIVE: To study erythrocyte immune function of patients with endometriosis
      and explore the pathogenesis of endometriosis. METHODS: 38 patients with
      endometriosis diagnosed by laparoscopy or laparotomy and 21 normal women as the
      control were studied. The patients were divided into three groups by revised
      American Fertility Society (RAFS) classification: group one (stage I, II; n =
      13), group two(stage III, n = 15), and group three(stage IV, n = 10). Using
      rosette formation test and polyethyleneglycol sedimentation methods, the
      erythrocyte immune function including C3b receptor rosette rate (C3bRR), immune
      complex rosette rate(ICR), erythrocyte rosette forming enhancing rate (RFER) and
      inhibitory rate (RFIR), and circulatory immune complex (CIC) was determined.
      RESULTS: The C3bRR, ICR, and RFER of group one, two, and three were decreased (P
      < 0.05 or P < 0.01), and RFIR and CIC of group one, two, and three were increased
      (P < 0.05) when compared with those of the control. All parameters had no
      significant difference among group one, two and three. In addition, these
      parameters had no significant difference in infertile groups of endometriosis as
      compared with those of fertile group. CONCLUSION: The erythrocyte immune function
      of patients with endometriosis is depressed, resulting from decreased erythrocyte
      immune adherence enhancer and increased inhibitor. These changes of erythrocyte
      immune function may be related to the pathogenesis of endometriosis.

PMID- 11326914
TI  - [Expression of integrin beta 3 and intracellular adhesion molecule in endometrium
      and endometriotic tissue].
AB  - OBJECTIVE: To study the relationship between integrin beta 3, intracellular
      adhesion molecule (ICAM) and endometriosis. METHODS: The expression of integrin
      beta 3 and ICAM protein were determined in 3 batches by immunoblotting method in
      15 endometrium and 15 endometriotic tissues of patients with endometriosis and 30
      endometrium from non-endometriosis subjects during the same menstrual phase. The
      results were scanned and semi-quantified, and then analysed by F test and t test.
      RESULTS: The results from 3 measurements showed the same trend. Endometrium from
      patients with endometriosis expressed significantly fewer integrin beta 3 and
      ICAM protein than those without endometriosis. On the other hand, the expression
      of integrin beta 3 in endometriotic tissue was significantly lower while the ICAM
      expression was significantly higher than those in controls. CONCLUSIONS: In
      patients with endometriosis, integrin beta 3 and ICAM expression changed
      significantly from eutopic to ectopic endometrium which may be related to the
      development of endometriosis and infertility.

PMID- 11326917
TI  - [Gonadotropin releasing hormone agonists in the treatment of adenomyosis with
      infertility].
AB  - OBJECTIVE: To Study the role of gonadotropin releasing hormone agonists (GnRH
      alpha) in the treatment of adenomyosis with infertility. METHODS: Adenomyosis was
      diagnosed under lapososcopy in 4 infertile cases. Meanwhile coexsting
      endometriosis, pelvic adhesion and adenomyoma were treated by surgery and
      endocoagulator in 4 and 2 cases respectively. GnRH-alpha (triptorelin or
      goserelin) therapy was given for six months before laparoscopic surgery in 1 case
      and after laparoscopic surgery in 3 cases. Their fecundity outcome were followed
      up after cessation of GnRH-alpha treatment. RESULTS: All cases became amenorrheic
      during GnRH-alpha therapy. The enlarged uteri all decreased to normal or near
      normal size. Menstruation returned in 80-90 days after cessation of treatment.
      Three cases conceived within four menstrual periods. One of them resulted in the
      birth of a healthy 3 150 g male at 38 weeks gestation by cesarean section. The
      second pregnancy resulting after adenomyomectomy was terminated by emergent
      cesarean section at 30 weeks gestation because of threatened rupture of uterus.
      The third is now normal at 28 weeks pregnancy. The fourth has had 2 menstrual
      periods and is still being followed up. CONCLUSION: (1) GnRH-alpha thus used is
      efficient in reducing the adenomyotic uterine size, and may facilitate fertility.
      (2) For ademyomata associated with infertility, GnRH-alpha therapy may avoid the
      risk of rupture of uterus which may occur after adenomyomectomy pregnancy. (3)
      For infertility, GnRH-alpha treatment before laparoscopic surgery greatly
      decreases surgical difficulties and blood loss in certain cases.

PMID- 11326916
TI  - [The expression of the receptors of estrogen, progesterone, epidermal growth
      factor and growth hormone in uterine adenomyosis and a comparative study after
      treatment with androgen].
AB  - OBJECTIVES: To investigate the pathogenesis of adenomyosis and its
      immunopathological study after treatment with androgen. METHODS: Estrogen
      receptor (ER), progestoren receptor (PR), epidermal growth factor receptor (EGFR)
      and growth hormone (GH) were determined by immunohistochemical SABC method in 30
      cases of adenomyosis (group I) and another 24 cases of adenomyosis accompanying
      leiomyoma (group II); ER, PR were determined with the same methods in 24 cases of
      adenomyosis who had been treated with methyltestosterone before operation (group
      III). RESULTS: (1) Both the eutopic and ectopic endometrium in group I showed ER,
      PR, EGFR, GH positive. The positive expression rate had no significant
      differences (P > 0.05). The strong positive rate of ER, PR in the eutopic
      endometrium were significantly higher than that in the ectopic (P < 0.05). (2)
      ER, PR, EGFR, GH in the eutopic and ectopic endometrium in group I and group II
      all showed positive but no significant differences (P > 0.05). (3) Both ER and PR
      showed positive in group I, II and group III. There were no significant
      differences (P > 0.05). (4) Among the 24 cases treated with androgen, the
      positive and strong positive rate of ER and PR in both eutopic and ectopic
      endometrium of 11 cases proved effective were higher than that of 13 ineffective
      cases and there were significant and striking differences (P < 0.05, < 0.01).
      CONCLUSIONS: ER, PR, EGFR, GH all expressed in the eutopic and ectopic
      endometrium. They played important roles in promoting the development of
      adenomyosis.

PMID- 11326918
TI  - [The relation between placental pathologic changes and serum nitric oxide levels
      of maternal and umbilical blood in intrauterine growth retardation].
AB  - OBJECTIVE: To study the relation between placental pathologic changes and levels
      of maternal and umbilical serum nitric oxide (NO) in intrauterine growth
      retardation (IUGR). METHODS: 38 patients with IUGR (IUGR group) and 30 healthy
      pregnant women in their late trimester (control group) were studied from Nov.
      1997 to Oct. 1998. The placenta and the appendages of fetus were studied after
      delivery. The concentration of serum NO were determined with cortas' method.
      RESULTS: Placental pathological changes were found in 26 cases of IUGR group
      (68.42%), and the main pathological changes were growth retardation of villi and
      villositis. In the control group, 5 out of 30 cases had placental pathological
      findings (16.67%). There was statistically significant difference between the 2
      groups (P < 0.01). In IUGR group, the maternal and umbilical NO concentration in
      the 26 cases with placental pathological changes decreased significantly when
      compared with that in 12 cases without obvious pathological findings of placenta
      (P < 0.05, P < 0.05); NO levels of umbilical cord were higher than that of
      maternal serum in both groups(P < 0.01, P < 0.05); There was correlation about
      serum NO concentration between mother and her fetus in both groups (r = 0.5475, r
      = 0.8506); but umbilical serum NO level was not related to the weight of the
      newborn (r = 0.2838). CONCLUSION: The obvious placental pathologic changes
      occurred in patient with IUGR caused noticeably lower NO levels in maternal and
      umbilical serum.

PMID- 11326919
TI  - [Clinical significance of changes of interleukin 6 level in pregnancy induced
      hypertension].
AB  - OBJECTIVE: To assess the clinical significance of changes of interleukin-6 (IL-6)
      level in patients with pregnancy induced hypertension (PIH). METHODS: IL-6 level
      in urine and blood were measured by sandwich enzyme labeled immunosorbent assay
      (ELISA) in 82 patients with PIH and 30 normal pregnant women. RESULTS: Blood IL-6
      level in severe PIH patients was significantly higher than that in mild PIH
      patients and normal pregnant women. IL-6 level of urine in PIH patients were
      significantly higher than that in normal pregnant women and was associated with
      the severity of disease. There was a positive correlation between urinary IL-6
      level and severity of renal damage in PIH. CONCLUSION: Determination of IL-6
      level is useful to understand the severity of PIH and its renal damage.

PMID- 11326920
TI  - [The effect of insulin-like growth factor I and insulin on intrauterine fetal
      growth retardation].
AB  - OBJECTIVE: To evaluate the role of insulin-like growth factor I (IGF-I) and
      insulin (Ins) in the occurrence of intrauterine fetal growth retardation (IUGR).
      METHODS: The study group included 17 women with IUGR, and 38 normal third
      trimester pregnant women were served as control. Maternal venous blood samples
      were collected from all cases before cesarean section. Umbilical venous blood and
      amniotic fluid were collected at the time of operation. The concentrations of Ins
      were measured by radioimmunoassay and concentrations of IGF-I were assayed by
      ELISA. RESULTS: The maternal serum IGF-I in IUGR group (117.29 micrograms/L) was
      significantly lower than that in the control group (207.07 micrograms/L) (P <
      0.002). The umbilical serum IGF-I in IUGR group (16.73 micrograms/L) was
      significantly lower than that in the control (44.89 micrograms/L) (P < 0.001).
      There was no significant difference of maternal serum Ins between IUGR group
      (12.18 mIU/L) and control group (7.13 mIU/L). CONCLUSIONS: The change of IGF-I
      and Ins levels in maternal and umbilical serum may play an important role in the
      pathophysiological changes in IUGR.

PMID- 11326921
TI  - [Study on the safety after cesarean section].
AB  - OBJECTIVE: In order to assess the safety after cesarean section, the
      complications and morbidity rate within 2 years after delivery between cesarean
      section and spontaneous delivery were compared. METHODS: A retrospective cohort
      study was used in this study. RESULTS: The prevalence of anemia, mobility
      restriction of uterus, chronic pelvic pain and wound ache during the 2 years
      postpartum in cesarean section group were 11.1%, 9.6%, 4.3% and 5.1%
      respectively, which were significantly higher than those in women with
      spontaneous delivery. CONCLUSION: In order to protect women's health, the
      indications for cesarean section must be mastered strictly.

PMID- 11326922
TI  - [Clinical significance of cardiac axis determination in prenatal
      echocardiographic diagnosis of fetal congenital heart disease].
AB  - OBJECTIVE: To investigate the clinical significance of cardiac axis determined by
      echocardiography in prenatal diagnosis of fetal congenital heart disease (CHD).
      METHODS: 518 high risk fetuses for CHD were and 90 normal fetuses were examined
      by echocardiography. Cardiac axis was measured on four-chamber view and fetal
      cardiac anatomical structure was examined in multiple views to determine CHD.
      RESULTS: The 35 fetuses with CHD diagnosed by prenatal echocardiography. There is
      significant difference of caidiac axis between CHD group (58.1 +/- 15.7 degree)
      and normal group (44.8 +/- 10.3 degree, P < 0.01). Sensitivity of CHD diagnosis
      using four-chamber view alone is 68.5%, it will be elevated to 91.4% by
      combination of four-chamber view and cardiac axis determination (P < 0.05).
      CONCLUSION: Cardiac axis play an important role in fetal echocardiographic
      screening for CHD and it should be measured routinely as part of the four-chamber
      view of the fetal heart. The normal range of fetal cardiac axis is 20 to 75
      degree. If it was more than 75 degree, the CHD should be suspected.

PMID- 11326923
TI  - [Study for the factors related to postpartum depression].
AB  - OBJECTIVE: To study the prevalence rate of postpartum depression(PD) and related
      factors. METHODS: 1,052 pregnant women were selected in random from our antenatal
      clinic from January to November, 1997 for mood study by hospital anxiety and
      depression (HAD), and 866 cases were further follow-up till 7 days after
      childbirth with Edinburgh postpartum depression scale (EPDS). RESULTS: The
      prevalence rate of PD was 15.01% by EPDS. Using single factor and mutifactorial
      stepwise regression analyses for the affected factors of PD, 7 factors were most
      strongly related to the onset of PD: they were women's health condition; the
      relationship between husband and wife; the medical workers' attitude during
      labor; husband's desire for boy child; the number of antenatal educational
      classes received; anxiety and depression mood during pregnancy. The number of
      educational classes received was negatively correlated with PD, while the other 6
      factors were all positively correlated. CONCLUSION: The main factors related to
      PD are the mood of anxiety and depression during pregnancy.

PMID- 11326924
TI  - [Analysis on the treatment of 1,020 patients with immunologic infertility].
AB  - OBJECTIVE: To investigate the treatment for immunologic infertility. METHODS:
      Serum antisperm antibody, anti-ovarian antibody, anti-endometrial antibody and
      anti-hCG antibody in 1,020 female patients with primary or secondary infertility
      were tested. Patients were treated with dexamethasone, vitamin E and vitamin C
      for 3 cycles consecutively as one course. RESULTS: The detective rates of the
      above antibodies were 25.88%, 22.86%, 32.81% and 23.61% respectively. After one
      course of treatment, the disappearance rates of the antibodies mentioned were
      over 90%, and the average pregnancy rate was up to 30%. CONCLUSION:
      Corticosterocls may reduce or even eliminate the effects of the immune factors on
      infertility.

PMID- 11326926
TI  - [Insulin-like growth factor and fetal development].

PMID- 11326925
TI  - [Expression of cytotrophoblast cell adhesion molecule and its relation with pre
      eclampsia].

PMID- 11326927
TI  - [Effects of integrins on the implantation of embryo, fetal development and
      obstetric and gynecologic diseases].

PMID- 11326928
TI  - [Clinical application of mifepristone in obstetrics and gynecology].

PMID- 11326929
TI  - [National symposium on clinical application of mifepristone in obstetrics and
      gynecology].

PMID- 11326930
TI  - [Termination of 10-16 weeks's gestation with mifepristone plus misoprostol: a
      multicentre randomized clinical trial].
AB  - OBJECTIVES: To find out the optimal regimen of mifepristone in combination with
      misoprostol for termination of 10-16 week's gestation. METHODS: A randomized
      comparative study in 2,007 women requesting medical abortion at 10-16 week's
      gestation from 24 hospitals was conducted in Shanghai. Women were randomly
      divided into 4 groups. In group I (n = 511) women took mifepristone 75 mg orally
      per day for 2 days (total dose 150 mg), and 48 hours later misoprostol 0.6 mg
      orally every 3-4 hours for 3 times; group II (n = 491) mifepristone 100 mg orally
      per day for 2 days (total dose 200 mg) and 48 hours later same dose of
      misoprostol were taken as in group I; group III (n = 519) same dose of
      mifepristone as in group I and 48 hours later misoprostol given vaginally every
      12 hours for 3 times; group IV (n = 486) same dose of mifepristone as in group II
      and 48 hours later same dose of misoprostol vaginally as in group III. RESULTS:
      The successful abortion rate from group I to group IV were 88.6%, 89.4%, 90.9%
      and 94.0% respectively. The successful abortion rate of group IV was higher than
      that in group I and II with significant differences (P < 0.05). The average dose
      of misoprostol by vaginal route in successful case was much lower than that by
      oral (P < 0.01), and the rate of side effects was much lower by vaginal too.
      CONCLUSION: Mifepristone taken 200 mg orally plus misoprostol vaginally is an
      optimal method for termination of 10-16 week's gestation.

PMID- 11326931
TI  - [Study of histopathology of endometrium following termination of early pregnancy
      using mifepristone].
AB  - OBJECTIVE: To explore the causes of abnormal uterine bleeding following
      termination of early pregnancy using mifepristone. METHODS: 19 specimens were
      obtained by curettage on the day immediately after expulsion of gestational sac,
      40 specimens on the 7th postabortal day and 20 specimens during 2-12 weeks after
      induced abortion using mifepristone respectively. The histopathologic changes of
      the specimens were observed by HE staining, and the expression of human choronic
      gonadotropin (hCG) and human placental lactogen (hPL) by immunohistochemical
      studies as well as phloxine-tartrazine staining and Gordon Sweets staining.
      RESULTS: It showed that decidua shedding retarded, especially basal decidua.
      Immunohistochemical studies demonstrated the trophoblasts were still active and
      might affect pathological changes of local endometrium. The specific granules of
      endometrial granulocytes disappeared, together with disintegration of the
      reticular fibers. But in the group which curettage was indicated for abnormal
      bleeding 2 weeks after abortion, the main cause was incomplete abortion.
      CONCLUSIONS: In addition to incomplete abortion, the retardation of decidua
      shedding and the impairment of endometrium regeneration were responsible for the
      abnormal uterine bleeding following termination of early pregnancy using
      mifepristone. The incomplete dissolution of the reticular fibers in basal decidua
      may induce decidua shedding retardation and incomplete abortion.

PMID- 11326932
TI  - [The immunohistochemical studies on estradiol and progesterone receptors in human
      decidua after terminating early pregnancy by mifepristone].
AB  - OBJECTIVE: To investigate the effects of mifepristone on decidua at the cellular
      level of estrogen receptor (ER) and progesterone receptor (PR) and the mechanism
      of prolonged uterine bleeding after terminating early pregnancy by mifepristone.
      METHODS: Thirty decidua specimens were obtained from pregnant women with
      amenorrhea of 6-7 week duration, 20 women were treated with mifepristone and 10
      given mifepristone plus misoprostol respectively. Immunocytochemical reactions of
      PR nad ER in decidua were compared among three groups using computer image
      analysis technology. RESULTS: In the control group, the nuclei of the decidual
      cells were stained positively for ER and PR. Their integral values of receptor
      level were 5,860,790 +/- 311,691 for ER and 4,905,970 +/- 157,319 for PR.
      Mifepristone treatment reduced ER and PR staining. The integral values were
      3,547,180 +/- 191,858 for ER and 3,700,750 +/- 188,322 for PR in this group, and
      it was more apparent in the group treated with mifepristone plus misoprostol:
      2,021,721 +/- 145,281 for ER and 2,528,580 +/- 240,535 for PR. CONCLUSIONS: The
      ER and PR level in human decidua decreased after mifepristone or/and misoprostol
      treatment. This may be related to prolonged uterine bleeding after terminating
      early pregnancy by mifepristone.

PMID- 11326933
TI  - [Effect of mifepristone on cell-cycle kinetics of human placental chorio
      trophoblastic and decidual cell].
AB  - OBJECTIVE: To study the effects of mifepristone on cell-cycle kinetics of human
      placental chorio-trophoblastic and decidual cells. METHODS: Flow-cytometry was
      introduced in the study of the mechanism of early pregnancy terminating drug,
      mifepristone. Twenty-three samples were obtained from normal pregnant women by
      surgical aspiration. Another 24 samples were obtained in women pretreated with
      150 mg mifepristone 48 hours before operation. RESULTS: The percentage of the
      cytotrophoblastic cells in G0 + G1 phases was much higher in the treatment group
      (P < 0.01), whereas it was much lower (P < 0.01) in G2 + M phases, and the
      proliferating index of cells was significantly decreased. Apart from the
      increasing of decidual cells in G2 + M phases (P < 0.05), there was no change in
      other phases. CONCLUSIONS: Mifepristone may block the transformation of the
      cytotrophoblastic cells from G0, G1 phases to S phase, thus leading to the block
      of the proliferation of cells. Mifepristone has much more significant effects on
      the chorionic villi than on the decidua.

PMID- 11326935
TI  - [Study of relation between ureaplasma urealyticum and fetal intrauterine growth
      retardation].
AB  - OBJECTIVE: To study the influences of Ureaplasma Urealyticum (UU) infection to
      fetal intrauterine growth. METHODS: Polymerase Chain Reaction was used to detect
      UU in samples of cervical secretions, umbilical blood and placenta. The study
      group included 50 women with neonatal birth weight below 2,500 g, 50 women with
      newborns birth weight above 2,500 g served as control group. RESULTS: Positive
      rate of UU in samples of cord blood and placenta and placental chorioamnionitis
      in study group were higher than that in the control group (P < 0.005 and P <
      0.05). There was no significant difference of UU positive rate in cervical
      samples between two groups. The positive rate of UU in cases with
      chorioamnionitis was higher than that of cases with negative UU infection (P <
      0.05). CONCLUSION: UU may interfere fetal intrauterine growth through infecting
      umbilical blood and placenta.

PMID- 11326934
TI  - [Study on decidual and villous cells apoptosis and its control gene in medical
      abortion].
AB  - OBJECTIVE: To study relationship of decidual and villous cells apoptosis and its
      control gene B-cell lymphoma/leukemia-2(bcl-2), bcl-2 associated X protein (bax)
      with medical abortion. METHODS: Forty four women who volunteered to terminate
      their pregnancy were divided into 3 group: mifepristone group (exp. 1, n = 15),
      mifepristone with misoprostol group (exp. II, n = 14) and control group (n = 15).
      The cell cycles of DNA of the decidual and villous cells stained with Propidium
      Iodide (PI) were analyzed and bcl-2 and bax gene protein labeled with immuno
      fluorescence were detected by flow cytometry. RESULTS: The percentage of decidual
      cells apoptosis were (14.0 +/- 3.9)%, (22.9 +/- 6.3)%, (5.3 +/- 9.3)% and of
      villous apoptosis were (10.9 +/- 2.8)%, (13.9 +/- 4.7)%, (4.6 +/- 3.0)% in exp.
      I, exp. II and control group respectively. The apoptotic percentages in decidual
      and villous cells of exp. I and exp. II groups were significantly higher than
      that of control (P < 0.01-0.001). On DNA histogram, apoptosis peaks appeared in
      all the groups. The decidual cell apoptosis of exp. II groups was significantly
      higher than that of exp. I group (P < 0.01). Both decidual apoptotic percentages
      of exp. I and exp. II groups were significantly higher than that of villous (P <
      0.01). Decidual bcl-2/bax ratio were 1.4 +/- 0.7, 0.9 +/- 0.3, 1.4 +/- 0.7 and
      villous bcl-2/bax ratio were 1.0 +/- 0.4, 0.8 +/- 0.3, 1.4 +/- 0.6 in the 3
      groups respectively. Both decidual and villous bcl-2/bax ratio of exp. II group
      was significantly lower than that of control (P < 0.05-0.01) which was in
      consistent with apoptosis. CONCLUSIONS: These data indicated that mifepristone
      with misocprostol for terminating human early pregnancy might be realized by
      inducing decidual and villous cells excessive apoptosis. The descent of bcl-2/bax
      ratio could be one of the factors of inducing decidual and villous apoptosis.

PMID- 11326937
TI  - [The treatment of intrauterine growth retardation with ant polyrhachis vicina
      roger].
AB  - OBJECTIVE: To study the growth promoting effect of ant Polyrhachis Vicina Roger.
      METHODS: Mated rats were divided into 3 groups, group A was non-smoking control
      group, group B was smoking induced intrauterine growth retardation (IUGR) group,
      group C was smoking induced IUGR rats fed with ant Polyrhachis Vicina Roger, then
      growth indices of fetal rats in each group were evaluated. RESULTS: The result
      showed that, the average birth weight, body length and tail length of fetal rats
      in treatment group were significantly higher than those of two control groups (P
      < 0.01); the incidence of IUGR was significantly lower in treatment group than
      that of two control groups (P < 0.01); the fetal mortality rate was significantly
      lower in treatment group than that of two control groups (P < 0.01). CONCLUSION:
      Ant Polyrhachis Vicina Roger is rich in amino acids, vitamines and trace
      elements, which could help the growth of fetal rats. Polyrhachis Vicina Roger is
      also rich in ecdysterone, that is growth hormone of insects, it has a strong
      protein anabolic effect, which might contribute to the growth promoting effect of
      Polyrhachis Vicina Roger.

PMID- 11326936
TI  - [Ureaplasma urealyticum infection and premature delivery or premature rupture of
      the membrane].
AB  - OBJECTIVE: To evaluate the relationships between ureaplasma urealyticum (UU)
      infection and premature delivery or premature rupture of the membrane (PROM).
      METHODS: The cervical swabs, fetal membrane and umbilical cord from 46 cases of
      PROM, 7 cases of premature delivery (study group), and 32 normal pregnancies
      (control group) were cultured for UU. Some of these placenta tissues were
      examined under electron microscopy, and compared with the purified UU. RESULTS:
      The detective rates of UU were both 73.6% (39/53) in the cervix and fetal
      membrane of the study group, and to compare with the control group (40.6%, 13/32
      and 15.6%, 5/32 respectively), significant differences were shown (P < 0.01, P <
      0.001). The prevalence rate of perinatal mortality, stillbirth and low birth
      weight in UU-positive cases (34.1%, 15/44) was significantly higher than that in
      UU-negative cases (7.3%, 3/41, P < 0.01). Electron microscopy demonstrated that
      large amount of small multiplicated UU particles deposited around the nuclear
      membrane of the cytotrophoblasts and in the collagen fibers from the placenta of
      PROM, and its shape was in consistent with that of the purified UU. In contrast,
      no UU particles was seen in the normal control group. CONCLUSION: The results
      show that UU is responsible for some cases of premature delivery, low birth
      weight and PROM. The multiplication of UU within the trophoblasts may disrupt
      cell structure which could interfere the normal fetal development.

PMID- 11326938
TI  - [Effect of conjugated estrogen and Org OD14 on serum lipoprotein and
      apolipoprotein in perimenopausal and postmenopausal women].
AB  - OBJECTIVE: To determine the effect of conjugated estrogen and Org OD14 on serum
      lipoprotein and apolipoprotein in perimenopausal women. METHOD: 74 patients were
      divided into 2 groups: 46 were given conjugated estrogen 0.625 mg and
      medroxyprogesterone acetate 4 mg daily according to the continuous sequential,
      regimen 28 were given Org OD14 2.5 mg every two days. Serum lipoprotein and
      apolipoprotein estradiol and follicle stimulating hormone were measured before
      and (one and two years) after treatment. RESULTS: Total Cholesterol (TC),
      Triglycerin (TG), high density lipoprotein (HDL-C), Apolipoprotein AI (Apo AI),
      Apolipoprotein AII (Apo AII), Apolipoprotein B(Apo B), Apolipoprotein CII(Apo
      CII), Apolipoprotein CIII(Apo CIII), Lipoprotein(a)[Lp(a)] increased
      significantly (P < 0.05), while ApoB/AI, ApoCII/CIII decreased significantly(P <
      0.05) in conjugated estrogen group. ApoCIII, E decreased, while ApoAI/AII
      increased significantly (P < 0.05) in Org OD14 group. After two years treatment,
      TC, HDL-C, ApoAI, ApoCIII, ApoE, TC, HDL-C, ApoAI, ApoCIII, ApoE of conjugated
      estrogen group were higher than those of Org OD14 group(P < 0.05), ApoCII/CIII of
      Conjugated estrogen was lower than that of Org OD14 group(P < 0.05). CONCLUSION:
      Postmenopausal hormone replacement therapy regulates the constitution of serum
      lipoprotein and apolipoprotein.

PMID- 11326940
TI  - [Detection of tumor cells in peripheral blood for patients with ovarian
      epithelial carcinoma].
AB  - OBJECTIVE: To detect tumor cell contamination of peripheral blood stem cell
      (PBSC) and the presence of tumor cells in peripheral circulating blood in
      patients with primary advanced ovarian cancer. METHODS: To establish limits of
      sensitivity of the immunocytochemical stainings technique (ABC method) for tumor
      cell detection, four types of ovarian cancer tumor cell(ovarian cancer cell lines
      SKOV3, 3AO, primary cancer cell from ascites of serous papillary carcinoma and
      undifferentiated adenocarcinoma) were added into normal blood to prepare the
      models with different ratios of tumor cells to mononuclear cells. Monoclonal
      antibodies(MAB) of COC 183 B2, CK(AE1/AE3) and their cocktail antibody (mixture
      of them) were used for immunocytochemical stainings. 14 blood specimens were
      examined (6 stem cell blood specimens, 8 primary advanced ovarian cancer blood
      spcimens). RESULTS: The sensitivity of detection achieved by cocktail antibodies
      was superior to either COC183B2 or CK MAb alone. The sensitivity of cocktail
      antibody was 1:5 x 10(5). According to the established sensitivity, none of the
      fourteen specimens contained tumor cell. CONCLUSIONS: None of the 6 PBSC
      specimens obtained from 2 patients and eight peripheral blood specimens obtained
      from 8 patients with primary ovarian epithelial carcinoma contained tumor cell.

PMID- 11326939
TI  - [Metastatic tumors of the vulva: a report of 78 cases].
AB  - OBJECTIVE: To study the clinical characteristics, diagnosis and reasonable
      therapy for metastatic tumors of vulva. METHODS: Seventy eight cases with
      metastatic tumors of the vulva were retrospectively reviewed. The cervical
      carcinoma was the most frequent primary site (61 cases), followed by the urethra
      (5 cases), vagina (4 cases), endometrium (3 cases), breast (2 cases), ovary (1
      cases), rectum carcinoma (1 cases) and malignant lymphoma (1 cases). RESULTS: The
      median age of this series was 55. 75.6%(59/78) of the patients subsequently
      developed vulvar metastasis from 15 days to 18 years after the primary tumors
      diagnosed, the median interval was 2.5 years. 61.5%(48/78) patients combined with
      primary site recurrence or other place metastasis, primary site recurrence were
      35.4%, inguinal lymph node metastasis 45.8%, supraclavicular lymph node
      metastasis 8.3%, pelvic metastasis 8.3% and hematogenous metastasis 12.5% (liver,
      lung, skeleton). Radiotherapy was the main therapeutic approch, some cases
      combined with surgery and/or chemotherapy. The overall 1 year, 3 years and 5
      years survival rates after vulvar metastatic occurrence were 65.4%, 29.5% and
      16.7% respectively. CONCLUSIONS: The prognosis of the vulva metastatic tumors was
      poor. Radiotherapy combine with surgery and/or chemotherapy can improve the
      survival.

PMID- 11326941
TI  - [Study of the inhibitory effects of retrovirus-mediated p16 gene on human ovarian
      cancer cell line].
AB  - OBJECTIVE: To study the inhibitory effects of retro-virus-mediated p16 gene on
      human ovarian cancer cell line CAOV3. METHODS: Recombinant eukaryotic expression
      vector pDOR-p16 containing exogenous human wt-p16 cDNA and vector with neomycin
      resistance gene only were introduced by lipofectamine-mediated gene transfection
      into CAOV3 cell line which does not express p16 endogenously. By using revert
      polymerase chain reaction amplification, mRNA in situ hybridization and
      immunocytochemistry, the clones obtained were detected for their efficiency of
      transfection and effects of vector expression and observed for their biologic
      behavior. RESULTS: Exogenous wt-p16 had successfully been transferred into CAVO3
      cells and obtained permanent expression. The growth rate of these transfected
      CAOV3 cells in regular medium and soft agar was inhibited, and the tumorigenicity
      in nude mice showed that two in four mice failed to form tumor and the others
      suffered from tumor later than contrast group by 7 to 14 days. The percentage of
      phase G1 cells increased and that of phase S cells decreased by analysing cell
      cycle. The ultrastructural changes of the cells were observed under electron
      microscope, revealing necrosis and growth retardation. CONCLUSIONS: p16 gene
      played an important role in generation and development of ovarian carcinoma. This
      study might provide the experimental evidence for the gene therapy in human
      ovarian cancer.

PMID- 11326942
TI  - [Progress in the study of oxytocin].

PMID- 11326944
TI  - [Laparoscopy in the diagnosis and treatment of malignant neoplasms in
      gynecology].

PMID- 11326945
TI  - [Oncogenes and tumor suppressor genes in lung cancer: research and trends].

PMID- 11326943
TI  - [Diagnosis and treatment of cervical pregnancy].

PMID- 11326946
TI  - [Experimental studies on human lung cancer gene-therapy with HSV-TK/GCV system].
AB  - OBJECTIVE: Evaluate the clinical potential of HSV-TK/GCV system in gene-therapy
      of tumors by using this system to treat human lung cancer A549 cells in vitro and
      in vivo. METHOD: The in vitro sensitivity levels of A549/TK (TK-tranfered A549)
      cells and wild type A549 cells to GCV were expressed as IC50 which was measured
      with MTT assay after treating both cells for 72 hrs. In vivo study, The nude mice
      bearing A549/TK tumor or A549 tumor were used as experimental models. All the
      animals were divided into 3 groups. Group 1, the animals bearing A549/TK tumor
      would be treated with GCV. Group 2, The animals bearing A549/TK tumor would be
      treated with saline. Group 3, The animals bearing A549 tumor would be treated
      with GCV. When the tumors reached to 200-300 mg the animals would be injected
      intraperitoneally with GCV solution (100 mg.kg-1.day-1) or equal volume of saline
      for two weeks. In this period and the following four weeks, the tumor weights
      were measured and calculated with the experience formula once every three or four
      days. RESULT: In vitro study showed that the A549/TK cells were apparently killed
      in a 20 mumol/L GCV solution while the wild type A549 cells grew normally under
      the same condition. The IC50 of A549/TK cells in GCV solution was 0.5 mumol/L and
      that of A549 cells 500 mumol/L, showing a 1,000 fold difference (P < 0.01). In
      vivo experiment GCV had compelled the A549/TK tumors to lead to a regression of
      92%, meanwhile the A549 tumors treated with GCV increased 3.9 times in weight in
      the first seventeen days of experiment. Group 2 tumors A549/TK tumors which were
      treated with saline, grew as well as group 3 did. There was a significant
      difference (P < 0.01) between group 1 and other groups. CONCLUSION: GCV could
      specifically and effectively kill the TK-transfered A549 cells in vitro and in
      vivo. This result suggested that the HSV-TK/GCV system may have a clinical
      potential for gene therapy of lung cancer.

PMID- 11326947
TI  - [Effects of exogenous wild type p53 on malignant growth of human lung cancer cell
      line].
AB  - OBJECTIVE: To study the effects of exogenous wild type p53 suppressor gene on
      malignant growths of human lung cancer cell line with mutant type p53 gene.
      METHOD: Four human lung cancer cell line were screened for mutations in the exon
      5 through exon 8 of the p53 tumor suppressor gene with immunohistochemistry,
      polymerase chain reaction (PCR)/single strand conformation polymorphism (SSCP)
      and DNA sequence analysis. The recombinent plasmid PZIPneoSV-p53 was constructed,
      which express wild type p53 gene. A transfected cell line, 801-D-p53, was
      obtained after transferred the plasmid into 801-D cell line by gene gun mediated
      and selected by G418. The exogenous p53 in the transfected cell line 801-D-p53
      were inspected with PCR, and the alteration of growths of the transfected cell
      line in vitro and in vivo was observed. RESULT: The point mutation were CGG to
      CTT transversion at codon 248 in exon 7 was found in human lung cancer cell line
      801-D by PCR-SSCP and DNA sequence analysis and nuclear accumulation of the p53
      protein was observed. The neo gene and exogenous wild type p53 gene were detected
      in the transfected cell line 801-D-p53. The cell growth experiment in vitro
      showed that the parent cell line 801-D growth was very fast, from 1 x 10(5)/ml to
      2.5 x 10(5)/ml within 6 days, the transfected PZIP-neo-SV cell line (plasmid
      without p53) growth as fast as 801-D, but the transfected cell line 801-D-p53
      growth was inhibited seriously. The clonogenic formation rate of the parent cell
      line 801-D, transfected cell line 801-D-PZIP and the transfected cell line 801-D
      p53 were 11.2%, 11.4% and 0.46% respectively. The clononogenic formation
      inhibition rate of the transfected 801-D-p53 was 96% comparing with the parent
      801-D cell line. In the experiment of xenogenic tumor transplantation, each cell
      line was injected subcutaneously into four mice and the growth of xenogenic tumor
      transplant in nude mice was observed. xenograft growth in all 4 mice in both 801
      D and 801-D-PZIP groups, but only 1 xenograft growth among 4 mice of 801-D-p53
      group during 2 months. The average volume of xenogenic tumor transplant of 801-D
      and 801-D-PZIP groups were 6.500 cm3 and 2.231 cm3 respectively and the only
      xenograft volume of 801-D-p53 group was 0.940 cm3. The tumorigenicity of 801-D
      p53 in nude mice was significantly suppressed. CONCLUSION: Exogenous wild type
      p53 gene may stably exist in the human lung cancer cell line with mutant type p53
      after plasmid transfection and suppressed the malignant growth of the transfected
      cell line 801-D-p53 in vitro and in vivo. These results indicate that the
      recombinent plasmid expressing wile type p53 may be useful for gene therapy of
      human lung cancer.

PMID- 11326948
TI  - [Diagnosis and surgical treatment of tuberculosis of mesentric lymph nodes].
AB  - OBJECTIVE: To evaluate the diagnosis, operative indication and therapeutic result
      of tuberculosis of mesentric lymph nodes. METHOD: Fifty-nine cases with
      tuberculosis of mesentric lymph nodes surgically treated at two hospitals from
      July 1976 to July 1997 were retrospectively analyzed. RESULT: Only 14 cases were
      correctly diagnosed before operation. Operative treatment for the tuberculosis of
      mesentric lymph nodes represented a safe, effective treatment with few
      complications and no operative death. CONCLUSION: Because patients with
      tuberculosis of mesentric lymph nodes show no characteristic manifestations,
      laboratory methods (e.g. polymerase chain reaction), peritoneoscopy, CT scanning
      and B mode ultrosound techniques should also be considered for diagnosis of the
      disease. The acute or chronic ileus, hemorrhage of digestive tract, intestinal
      perforation or fistula, intra-abdominal large tuberculous abscess and abdominal
      sinus caused by tuberculosis of mesentric lymph nodes should be surgically
      treated. The exploratory laparotomy also should be performed on the patients with
      abdominal mass or those whose diagnosis of neoplasm could not be ruled out. The
      postoperative antituberculosis chemotherapy should be continued to decrease the
      occurrence of complications.

PMID- 11326949
TI  - [Arthroscopy in diagnosis and treatment of tuberculous synovitis].
AB  - OBJECTIVE: To evaluate the role of arthroscopy in the diagnosis and treatment of
      early tuberculous synovitis. METHOD: Eighteen patients with monoarticular
      synovitis who underwent arthroscopy and diagnosed as tuberculous synovitis
      because of arthroscopic findings and synovial biopsies from September 1986 to
      September 1996 were reviewed. RESULT: Four out of 18 patients were diagnosed on
      the basis of clinical manifestations and laboratory results before operation, and
      proved pathologically after operation. The other 14 cases were definitely
      diagnosed by arthroscopy and pathological examination. With an average of 3 years
      and 4 months follow-up, the results of the treatment were excellent. Symptoms
      disappeared, and full joint functions restored in each case. CONCLUSION:
      Arthroscopy is a useful method in the diagnosis and treatment of early
      tuberculous synovitis.

PMID- 11326950
TI  - [Pathological changes of early intestinal tuberculosis].
AB  - OBJECTIVE: To probe into the characteristics of pathological changes of early
      intestinal tuberculosis. METHOD: Three cases of early intestinal tuberculosis
      proved by colonoscopy were reported and analyzed. RESULT: Hyperemia and edema of
      the ileocecal mucosa were found. The involved mucosa looked friable and eroded,
      which was covered by fibrinopurulent exudates or forsty white mucus. The
      ileocecal valve was edematous and deformed. Tuberculous tubercles were found in
      intramucosal tissue under microscopy. Neither ulceration nor fiberous hypertrophy
      was found. CONCLUSION: It shows important significance to recognize the
      pathological manifestations of early intestinal tuberculosis for diagnosis of the
      disease.

PMID- 11326951
TI  - [Clinical study on acute respiratory infection caused by chlamydia pneumoniae].
AB  - OBJECTIVE: To find out the infected rate and the clinical features of patients
      with acute respiratory infection caused by chlamydia pneumonia(C. pneumoniae).
      METHOD: A prospective study for chlamydia pneumoniae infection was conducted in
      110 patients with respiratory tract infection from January to December 1995 in
      Nanjing. Sputum and throat swab specimens were taken and C. pneumoniae DNA were
      detected by polymerase chain reaction (PCR) with the HM-1-HR-1 primer pair. At
      the same time, serum samples were taken and immunoglobulins G and M (IgG and IgM)
      fractions of antibodies to C. pneumoniae were studied by microimmunofluorescence
      test. RESULT: Prevalence of specific IgG was 70% in patients with respiratory
      tract infection. Seventeen patients (16%) were serologically diagnosed as having
      recent C. pneumoniae infection and 12 patients (11%) had the positive PCR in
      sputum and/or swab specimens. The total positive rate was 23% (25/110) combining
      PCR with serology. Acute infection of C. pneumoniae was common in the patients
      with asthma (57%), pneumonia (35%), COPD (26%) and bronchitis (25%). The clinical
      feature between C. pneumonia infection (n = 5) and non-C. pneumonia infection (n
      = 85) was not significanty different. CONCLUSION: Data suggest that Chlamydia
      pneumonia is an important pathogen that causes infections of the human
      respiratory tract and attention should be drawn to this special illness.

PMID- 11326952
TI  - [The long-term effect of double embolization of bronchial artery on patients with
      hemoptysis].
AB  - OBJECTIVE: To investigate the long-term effect of bronchial arterial embolization
      with different material and procedure on patients with hemoptysis. METHOD:
      Seventy two cases were divided into two groups, one received the double
      embolization of bronchial artery, the other group used single gelfoam
      embolization. In double embolization group, the mixture containing gelfoam
      microspheres (0.5 mm x 0.5 mm), erythromycin and high osmalality sodium chloride
      were firstly used to embolize the terminal vessels, the gelfoam particle (1 mm x
      1 mm) was then used to embolize the main trunk of bronchial artery. RESULT: After
      2-4.8 years following up, it turned out that the cure rate and general
      effectiveness were: the double embolization group 83%, 100% respectively, the
      single gelfoam embolization group 61%, 95%. By comparison, there were significant
      difference on cure rate between these two groups(P < 0.05). CONCLUSION: The
      bronchial arterial double embolization will increase the long-term effect
      obviously on patients with hemoptysis.

PMID- 11326953
TI  - [The effect of herbal medicine including astragalus membranaceus (fisch) bge,
      codonpsis pilosula and glycyrrhiza uralensis fisch on airway responsiveness].
AB  - OBJECTIVE: To study the effect of astragalus membranceus(fisch) bge, codonpsis
      pilosula and glycyrrhiza uralensis fisch on airway responsiveness. METHOD: FVC,
      FEV1 and PEF of twenty-eight asthmatic patients were measured before and six
      weeks after treated with Astragalus membranceus(fisch) bge, codonpsis pilosual
      and glycyrrhiza uralensis fisch; methacholine challenge test with 0.033 mumol and
      1.98 mumol. RESULT: After 28 asthmatic patients received the treatment of those
      herbs, the results showed that FVC value increased obviously (t = 2.217, P <
      0.05) and the value of FEV1 and PEF was all higher compared with before treatment
      of the herbs (P < 0.01). CONCLUSION: The herbal medicine including astragalus
      memberanaceus (fisch) bge, codonpsis pilosual and glycyrrhiza uralensis fisch can
      decrease the airway responsiveness of the patients with asthma.

PMID- 11326954
TI  - [Study on HSP70, 90 mRNA gene expression in peripheral blood mononuclear cells
      with steroid-resistant asthmatics].
AB  - OBJECTIVE: To investigate the role of heat shock protein(HSP) 70, 90 alpha, 90
      beta mRNA on the pathogenesis of steroid-resistant(SR) asthma. METHOD: 9 SR
      asthmadics 16 steroid sensitive (SS) asthmatics and 10 normal healthy volunteers
      were studied. With reverse transcription-polymerase chain reaction(RT-PCR), the
      expression of hsp70, 90 alpha, 90 beta mRNA were detected in peripheral blood
      mononuclear cell(PMBC) from normal volunteers and SR. steroid-sensitive(SS)
      asthmatics. Inhibition of PHA-induced lymphocyte proliferation by dexamethasones
      (Dex) was investigated using lymphocyte proliferation assay. RESULT: There were
      no expression of hsp70mRNA in PMBC of normal volunteers; the levels of expression
      of hsp70, 90 alpha, 90 beta mRNA in PBMC of SR asthmatics (70 = 2.95 +/- 1.12, 90
      alpha = 2.17 +/- 0.89, 90 beta = 2.22 +/- 0.83) were significantly higher than SS
      asthmatics (70 = 0.23 +/- 0.09, 90 alpha = 1.07 +/- 0.39, 90 beta = 0.94 +/-
      0.32) (P < 0.01) and normal volunteers (70 = 0, 90 alpha = 0.45 +/- 0.19, 90 beta
      = 0.32 +/- 0.15) (P < 0.01); There were significantly positive correlation
      between the degree of inhibition by Dex(10(-7) mol/L) of SR, SS asthmatics of
      proliferation of T lymphocytes and the expression of hsp70, 90 alpha, 90 beta
      mRNA in PMBC(P < 0.01). CONCLUSION: There were expression of hsp70, 90 alpha, 90
      beta gene in PMBC from SR asthmatics, but increased with worsening of
      inflammation and prolonging of the duration of disease. The more hsp 90 gene
      expression, the less T lymphocytes were inhibited by Dex.

PMID- 11326955
TI  - [Detection of ET-1, TNF-alpha, oxidative radicals in sera of asthmatics and in
      sera and lung tissue of asthmatic guinea pigs].
AB  - OBJECTIVE: To investigate the role of the ET-1, TNF-alpha and oxidative radicals
      of MDA and SOD in the pathogenesis of asthma and the effect of the nitric oxide
      synthase inhibitor, L-NAME to above factors. METHOD: ET-1 was detected by the
      radio-immunoassay and TNF-alpha was detected by ELISA, SOD and MDA were detected
      by using thiobarbituric acid method. RESULT: The contents of ET-1, TNF(and MDA in
      the serum of the asthmatic patients and in the serum and lung tissue of asthma
      models of guinea pigs were significantly increased, in the contrast, the content
      of SOD was decreased compared with those in the controls(P < 0.01). All the
      changes in the serum and in the lung tissues of the asthma models of guinea pigs
      returned to the levels of the controls by dexamethasone inhalation or L-NAME by
      intraperitoneal injection. CONCLUSION: ET-1, TNF alpha and the oxidative radicals
      and NO may play important roles in the pathogenesis of asthma, L-NAME, which is
      similar to the dexathamethsone, may either decrease the content of NO or decrease
      the content of ET-1, TNF alpha and oxidative radicals in asthma.

PMID- 11326956
TI  - [Level of NCF and TNF-alpha in the BALF of ILD patients and their clinical
      significance].
AB  - OBJECTIVE: To investigate the relationship between the level of the neutrophil
      chemotactic factor(NCF), tumor necrosis factor-alpha(TNF-alpha) in patients with
      interstitial lung disease(ILD) and the activity of ILD. METHOD: The NCF
      activities in the BALF and in the serum from 11 patients with sarcoidosis, 7 with
      idiopathic pulmonary fibrosis (IPF) and 8 normal subjects were determined using
      the membrane filter and radio-immunoassay. The level of TNF-alpha was also
      detected. RESULT: In the 7 IPF patients, the level of NCF and TNF-alpha (203 +/-
      44 cells/10 HP, 11.7 +/- 2.9 ng/L) in the BALF was higher than that in 8 control
      patients (83 +/- 45 cells/10 HP, 6.5 +/- 1.4 ng/L, P < 0.01). The level of NCF
      and TNF-alpha in the BALF from 11 patients with sarcoidosis (186 +/- 50 cells/10
      HP, 12 +/- 3 ng/L) was highet than those in 8 control patients (P < 0.01). The
      level of NCF and TNF-alpha in the BALF from patients with IPF was positive
      correlated with the percentage of neutrophil (NCF: r = 0.89, P < 0.01; TNF-alpha:
      r = 0.86, P < 0.05). The level of NCF and TNF-alpha in the BALF of patients with
      sarcoidosis was positive correlated with the percentage of lymphocyte (NCF: r =
      0.78, P < 0.01; TNF-alpha: r = 0.73, P < 0.01. CONCLUSION: The level of NCF and
      TNF-alpha in the BALF from patients with IPF and sarcoidosis can act as the
      marker of the activity of alveolitis of IPF and sarcoidosis.

PMID- 11326957
TI  - [Spironolactone ameliorates rat pulmonary fibrosis induced by bleomycin A5].
AB  - OBJECTIVE: The purpose of this study was to investigate the role of aldosterone
      in pulmonary fibrosis and the protective effect of anti-aldosterone treatment.
      METHOD: Rats were divided into control, fibrosis and treatment groups; rat
      pulmonary fibrosis was induced by endotracheal injection of bleomycin A5 and
      spironolactone was given 100 mg/kg daily in drinking water to treatment group. 28
      days later, plasma, bronchoalveolar lavage fluid(BALF) and tissue aldosterone
      concentration, as well as lung collagen levels, were determined. RESULT: Plasma
      aldosterone was higher in fibrosis group than that in control group(469 +/- 161
      pg/ml and 319 +/- 115 pg/ml, respectively), but without significant difference (P
      > 0.05); spironolactone could ameliorate the extent of pulmonary fibrosis, the
      level of lung collagen was 25% less than that of fibrosis group (3.4 +/- 0.5 mg/g
      lung and 4.6 +/- 1.2 mg/g lung, respectively; q = 3.7893, P < 0.05), and the
      level of lung protein was 22% less (50 +/- 4 mg/g lung and 65 +/- 6 mg/g lung,
      respectively; P < 0.01). CONCLUSION: Spironolactone had some protective effects
      on pulmonary fibrosis, and aldosterone might play a role in the development of
      pulmonary fibrosis.

PMID- 11326958
TI  - [Morphometric investigation on hypoxic structural remodeling of intraacinar
      pulmonary arteries].
AB  - OBJECTIVE: To observe the inhibitory effects of Radix Astragali (RA) on hypoxic
      structural remodeling of intraacinar pulmonary arteries (IAPA) and pulmonary
      hypertension (PHT). METHOD: 60 rats were divided into H (hypoxia) group (n = 20
      rats) H + RA group (n = 20) and normal control (C) group (n = 20). The rats of H
      group and H + RA group were fed in hypoxic environment under normal atmospheric
      pressure (10% O2, 10 hours/day). On the 15th and 30th day of hypoxia, right
      ventricular systolic pressure (RVSP) and right ventricle hypertrophy index (RVHI)
      were measured and pulmonary vessel changes were studied under light and electron
      microscope with morphometric analysis. RESULT: Compared with H + RA group on 30th
      day, RVSP in H was 1.8 time as high as that of H + RA(P < 0.05); RVHI in H was
      1.3 time as high as that of H + RA (P < 0.05); the media thickness of IAPA in H
      was 2.3 time as high as that of H + RA (P < 0.05); the density of adventitial
      fibroblasts of IAPA was 13.1 +/- 0.3 (H) and 7.6 +/- 0.2 (H + RA) (P < 0.05).
      CONCLUSION: Preserving the IAPA wall cells and dilating IAPA by RA may play an
      important role in inhibiting remodeling of IAPA and PTH.

PMID- 11326959
TI  - [Progress in the lung cancer therapy with angiogenesis inhibitors].

PMID- 11326960
TI  - [Antitubercular drug-induced liver injuries].

PMID- 11326961
TI  - [Prospects in the treatment of pulmonary hypertension with nitric oxide].

PMID- 11326962
TI  - [L-arginine prolonged the efficacy of inhaled nitric oxide on the inhibition of
      pulmonary hypertension].
AB  - OBJECTIVE: The aim of this study is to investigate the effects of L-arginine, the
      substrate of nitric oxide (NO) on the duration of nitric oxide selective decrease
      of pulmonary hypertension. To assess whether combined use of inhaled nitric oxide
      and venous administered L-arginine can improve the efficacy of inhaled NO on the
      inhibition of hypoxia induced pulmonary hypertension. METHOD: Eight pigs with
      hypoxic pulmonary hypertension received either inhaled NO(12-15 ppm) for 10
      minutes or inhaled NO plus venous administrered L-arginine(10 g), then
      hemodynamic parameters were recorded. RESULT: NO inhalation significantly
      inhibited hypoxic induced pulmonary hypertension with pulmonary arterial pressure
      decreasing from 4.2 +/- 0.4 kPa to 2.5 +/- 0.5 kPa(P < 0.01) and pulmonary
      vascular resistance from 56 +/- 25 kPa.s.L-1 to 31 +/- 13 kPa.s.L-1(P < 0.01),
      but this just lasted for 3-5 minutes after stopping inhalation; combined use of L
      arginine infusion did not further decrease pulmonary arterial pressure, but
      significantly prolonged the inhibitory effect of inhaled NO on pulmonary
      hypertension (20 times) as compared with inhaled NO only. CONCLUSION: With the
      existence of exogenous NO, supplement of NO substrate L-arginine produced a
      synesgetic inhibition effect on hypoxic induced pulmonary hypertension.

PMID- 11326963
TI  - [The role of nitric oxide and nitric oxide synthase in the pathogenesis of
      asthma].
AB  - OBJECTIVE: To investigate the role of nitric oxide (NO) and nitric oxide synthase
      (NOS) in the pathogenesis of asthma. METHOD: 52 guinea pigs were randomly divided
      into four groups of 13 each: (1) asthmatic group (Group A): Dunkin-Hartley guinea
      pigs were injected celiacly with 1 ml of 10% ovalbumin (OA). After 14 days, the
      animals were inhaled with an aerosol of 1% OA for 40-60 seconds for 10 days every
      other day; (2) Corticosteroid prevention group (Group CT): As above, just before
      the animals were inhaled with an aerosol, 0.5 mg/kg dexamethasone were injected
      celiacly; (3) N-nitro-L arginine prevention group (Group L): As Group A, just
      before the animals were inhaled with an aerosol, 0.4 mg/kg LNNA were injected
      celiacly; (4) Controls (Group C): and nitrate (NO2.-/NO3.-) levels in plasma,
      nitrite bronchoalveolar lavage fluid (BALF) and lung tissues were examined. At
      the same time, inducible nitric oxide synthase (iNOS) and constitute nitric oxide
      synthase (cNOS) activity levels in the lung tissues were examined, and the
      changes of cNOS in the guinea pig asthma model lung tissues were observed using
      histochemical detection. RESULT: All groups had no significant alteration of NO2.
      /NO3.- in the plasma (P > 0.05). Group A had increased amounts of NO2.-/NO3.- in
      the BALF and in the lung tissues compared with the other groups (BALF: Group A
      10.2 +/- 1.3, Group CT 7.2 +/- 1.1, Group L 7.3 +/- 1.3, Group C 6.2 +/- 0.8
      mumol/L respectively, all of P < 0.01; the lung tissues: Group A 0.89 +/- 0.07,
      Group CT 0.16 +/- 0.09, Group L 0.24 +/- 0.09, Group C 0.18 +/- 0.05 nmol/mg
      respectively, all of P < 0.01). Group A also showed increased amounts of iNOS
      levels in the lung tissues than the other groups (Group A 59 +/- 18, Group CT 10
      +/- 5, Group L 12 +/- 7, Group C 10 +/- 5 pmol/mg respectively, all of P < 0.01).
      Group L showed decreased amounts of cNOS levels in the lung tissues than the
      Group C (0.8 +/- 0.4, 1.2 +/- 0.4 fmol/mg, P < 0.05). While there were no
      significant alterations in the other groups (P > 0.05). Elevation of iNOS in the
      lung tissues was correlated with NO2-/NO3- in the BALF and in the lung tissues (r
      = 0.714, 0.842, respectively, P < 0.05, 0.01 respectively). NADPHd was found to
      be a histochemical marker reflecting cNOS activity. It was found that there was
      no marked alteration of cNOS activity in the Group A, Group CT and Group C, but
      lower in the Group L. CONCLUSION: There is increased production of iNOS in
      asthmatic guinea pigs, the iNOS produced could cause increased production of NO,
      and probably cause cytotoxicity and mediate airway hyperresponsiveness. NO and
      NOS may play an important role in the pathogenesis of asthma.

PMID- 11326964
TI  - [Effects of nitric oxide on the airway inflammation and lymphocyte proliferation
      in sensitized rats].
AB  - OBJECTIVE: To investigate the relations between intrinsic nitric oxide (NO) and
      airway inflammation and lymphocyte proliferation in bronchial asthma. METHOD: The
      rat model of asthmatic airway inflammation was established by first sensitizing
      and then challenging the animals with ovalbumin. NO synthase (NOS) inhibitor and
      NO precursor were then applied and their influences on the airway inflammatory
      cell numbers and on the numbers of mIL-2R positive lymphocytes were observed.
      RESULT: In vivo experiments showed that normal control rats (n = 6) did not have
      eosinophils in their submucosal of airways while in the sensitized animals (n =
      6) eosinophils [23 +/- 5 (average cell counts per microscopic visual field, the
      same below) as well as lymphocytes (34 +/- 5) and mIL-2R positive cells (12 +/-
      3) were found in significantly increased numbers in the airways. The application
      of NOS inhibitor significantly reduced eosinophils (13 + 3, P < 0.05) and mIL-2R
      positive cells (4.3 +/- 1.6, P < 0.05) in the sensitized animals and the number
      of lymphocytes was also decreased (28 +/- 4) although it did not reach the
      significant level. At the same time the spleen cell proliferation was inhibited
      (P < 0.05) and the mIL-2R positive spleen cell numbers were reduced (P < 0.05).
      On the contrary, the application of NO precursor resulted in the further increase
      of the numbers of eosinophils, lymphocytes and mIL-2R positive cells although the
      differences were not statistically significant. In vitro experiments showed that
      NOS inhibitor inhibited the proliferation of cultured spleen lymphocytes as well
      as their mIL-2R expression (P < 0.05). NO precursor, when used in low dose, could
      promote the proliferation and mIL-2R expression of spleen cells (P < 0.05); but
      high dose of it showed inhibiting effect on the spleen cells (P < 0.05).
      CONCLUSION: Intrinsic NO at a suitable level is important in the regulation of
      the proliferation and activation of lymphocytes in the airways with allergic
      inflammation in the sensitized rats. This research is conducive to the
      understanding of the pathogenesis of the asthmatic airway inflammation and to
      investigating of new therapeutic approaches.

PMID- 11326965
TI  - [Low-concentration nitrous oxide inhalation in the treatment of high-altitude
      pulmonary edema].
AB  - OBJECTIVE: To investigate the therapeutic effect of low-concentration of nitroic
      oxide (NO) inhalation in high-altitude pulmonary edema. METHOD: Sixty-five male
      patients with high-altitude pulmonary edema were randomized into three groups.
      Patients in the conventional therapy group received oxygen, intravenous
      furosemide, aminophylline and dexamethasone; patients in the nifedipine group
      received oral nifedipine (10 mg, tid) in addition to conventional therapy; and
      patients in the NO group received NO (10 ppm) inhalation for 30 min, in addition
      to oral nifedipine. The time for which pulmonary rales on auscultation and
      shadows on chest radiograph lasted, and the course of disease, were compared.
      RESULT: In the NO group, pulmonary rales disappeared in 0.4 +/- 0.3 d, shadows on
      chest radiograph disappeared in 0.6 +/- 0.2 d, and the course of disease was 1.8
      +/- 0.7 d, all of which were significantly different from those of the nifedipine
      group (2.4 +/- 1.4 d, 4.1 +/- 1.7 d, 6.8 +/- 1.8 d, respectively) and the
      conventional therapy group (3.7 +/- 1.2 d, 5.5 +/- 1.8 d, 9.6 +/- 3.1 d,
      respectively). CONCLUSION: Low-concentration NO inhalation on the basis of
      conventional and nifedipine therapies was very effective in the treatment of high
      altitude pulmonary edema, which deserves further and larger scale investigation.

PMID- 11326966
TI  - [The correlative study on nitric oxide and cotinine nicotine metabolite in
      smokers' urine].
AB  - OBJECTIVE: In order to observe the changes of nitric oxide (NO) affected by
      smoking and their relationship in vivo. METHOD: 60 male nonsmoker as the control
      group, 192 male smoked as the study group which was divided into 4 subgroups (1
      10, 11-20, 21-30 and > 30) according to the number of cigarettes smoked per day.
      The metabolite of nicotine-cotinine in urine was assayed by means of barbituric
      acid. Cotinine was used as an objective indicator to reflect the smoking
      quantity. The urinary NO (NO2.-) was determined with colorimetric estimation.
      RESULT: The urinary cotinine level in the 4 subgroups were 6.6 +/- 1.6, 25.1 +/-
      6.2, 37.8 +/- 8.5, 53.6 +/- 8.3 (mumol/L) respectively. The urinary NO of
      nonsmokers were 4.43 +/- 0.97 (mumol/L), in the 4 subgroups it was 3.04 +/- 0.07,
      2.75 +/- 0.05, 2.18 +/- 0.01, 1.60 +/- 0.01 (mumol/L) respectively. The results
      of statistical analysis between the 4 subgroups were t = 4.2894, P < 0.01; t =
      2.7446, P < 0.01; t = 2.7667, P < 0.01 accordingly. As compared between the 4
      subgroups of smokers and the nonsmokers, the statistical results were t = 2.7118,
      P < 0.01; t = 3.1826, P < 0.01; t = 3.2100, P < 0.01; t = 4.6600, P < 0.01;
      respectively. The statistical differences between the 4 subgroups were t =
      2.9286, P < 0.01; t = 3.0357, P < 0.01; t = 3.8181, P < 0.01; t = 2.2160, P <
      0.05 respectively. There was a good positive correlation between the number of
      cigarette smoked and urinary cotinine content (r = 0.8626, P < 0.01), also a
      significant negative correlation between it and urinary NO level (r = -0.6596, P
      < 0.05). A negative correlation could be observed between urinary cotinine and NO
      (r = -0.6026, P < 0.05). CONCLUSION: With the increase of quantity and duration
      of smoking, the NO content in vivo will decrease, suggested that the vascular
      endothelial cells could be damaged severely.

PMID- 11326967
TI  - [Effects of smoking on the lipid peroxides antioxidation and alpha 1
      antitrypsin].
AB  - OBJECTIVE: Detecting free radicals and alpha 1-antitrypsin (alpha 1-AT) from
      healthy smoker's blood to study the action of free radicals in smoking induced
      diseases. METHOD: Thiobarbituric acid method (TBA), RIA, 5-5'-dithio-2
      dinitrobenzoicacid (DTNB) method, Ellman method and enzyme linked immunosorbent
      assay were used to detect the lipid peroxides (LPO), superoxide dismutase (SOD),
      glutathione peroxidase (GSH-px), glutathione (GSH) and alpha 1-AT. RESULT: In the
      blood of nonsmokers, LPO was 4.9 +/- 2.5 mumol/L, SOD was 878 +/- 302 ng/g Hb,
      GSH-px was 120 +/- 35 U, GSH was 3.4 +/- 0.7 mmol/L, alpha 1-AT was 75 +/- 11
      mg/L, in the blood of smokers, they were 6.1 +/- 3.0 mumol/L, 780 +/- 282 ng/g
      Hb, 112 +/- 34 U, 3.1 +/- 0.8 mmol/L, 71 +/- 15 mg/L respectively. The LPO
      content in the blood of smokers was significant higher than that of nonsmokers (P
      < 0.01), but the SOD GSH-px GSH and alpha 1-AT contents measured was significant
      lower (P < 0.05 or P < 0.01). CONCLUSION: The increase of oxidation and decrease
      of antioxidation, activity of alpha 1-AT and imbalance of protease and
      antiprotease might play important roleg in smoking induced diseases.

PMID- 11326969
TI  - [Diverse effects of glucocorticoids on diverse leucocytes apoptosis].
AB  - OBJECTIVE: To observe effects of glucocorticoids on the process of apoptosis in
      main inflammatory cells related to pulmonary inflammation. METHOD: Human
      peripheral blood neutrophil(PMN), eosinophil (EOS) and T lymphocyte(TLC) were
      cultured in vitro under glucocorticoids condition. In situ end-labeling technique
      of fragmented DNA was used to detect the dynamic fesatures of apoptosisin
      experimental collected cell. The peripheral PMN apoptosis in acute respiratory
      distress syndrome(ARDS) and EOS, TLC apoptosis in bronchial asthma were
      determined by the same method before and after treatment with glucocorticoids.
      RESULT: PMN, EOS and TLC showed signs of apoptosis spontaneously and no signs of
      surviving cells after 12 h/43 h, 15 h/65 h and 65 h/128 h of culture
      respectively. Dexamethasone accelerated EOS and TLC apoptosis, while inhibited
      PMN apoptosis. The PMN apoptosis in ARDS and EOS, TLC apoptosis in bronchial
      asthma were in various degreof inhibitory state. The above time of PMN, EOS and
      TLC apoptosis were 41.5 h/92.6 h,29.3 h/100 h,92.4 h/152.2 h respectively. The
      inhibitory state of PMN apoptosis was not influenced by glucocorticoids therapy,
      but the EOS and TLC apoptosis were relieved from their inhibitory state.
      CONCLUSION: Effects of glucocorticoids are different in diverse leucocyte
      apoptosis. This could have an differential significance in pulmonary
      inflammation.

PMID- 11326968
TI  - [Expressions of TNF alpha, PDGF in alveolar type II epithelial cells of rats with
      bleomycin-induced pulmonary fibrosis].
AB  - OBJECTIVE: The expressions of TNF alpha and PDGF in alveolar type II epithelial
      cells of rats with bleomycin(BLM)-induced pulmonary fibrosis were studied.
      METHOD: A single intratracheal injection of BLM was administrated to induce
      pulmonary fibrosis of rats. Animals were killed at day 3,7,14 and 28 after BLM
      administration. The immunohistochemical methods were used to analyze the
      expressions of TNF alpha and PDGF proteins in alveolar epithelium of rats. The
      total RNA was extracted from the alveolar type II epithelial cells of rats and
      the expressions of TNF alpha and PDGF mRNA were analyzed with Northern blot.
      RESULT: TNF alpha and PDGF were expressed in the alveolar type II epithelial
      cells of BLM-administrated rats. The expression of TNF alpha elevated in median
      and late-stage of the process and reached the peak at day 28. While the
      expression of PDGF elevated in early-stage and reached the peak at day 7. By
      contrast, TNF alpha and PDGF weren't expressed in the alveolar type II epithelial
      cells of normal controls. CONCLUSION: The results show that the alveolar type II
      epithelial cell from rats with pulmonary fibrosis overexpresses TNF alpha and
      PDGF and they may play roles in the pathogenesis of lung fibrosis.

PMID- 11326970
TI  - [The expression of Fas antigen on lymphocytes in the patients with asthma].
AB  - OBJECTIVE: To study the expression of Fas antigen on lymphocytes in patients with
      asthma. METHOD: The peripheral blood lymphocytes (PBL) isolated from patients
      with asthma were cultured with dexamethasone 10(-5) mol/L, Fas antigen on
      lymphocytes was detected by flow cytometry at 0, 2nd, 8th, 24th hour
      respectively. RESULT: The native expression of Fas antigen of PBL isolated from
      the patients with asthma (5.3% +/- 2.0%, P < 0.05) was lower than that from
      healthy controls (8.5% +/- 1.8%). Increased expression of Fas antigen in the
      patients with asthma was observed with induction of dexamethasone (P < 0.01). The
      percentages of Fas positive cell were 5.3% +/- 2.0%, 33% +/- 5%, 63% +/- 11%, 76%
      +/- 7% at 0, 2nd, 8th, 24th hour respectively in asthmatic group. While 8.5% +/-
      1.8%, 31% +/- 11%, 49% +/- 10%, 20% +/- 4% respectively in normal control group.
      CONCLUSION: Decreased native expression of Fas on lymphocytes may be related to
      airway inflammation in the patients with asthma. Increased expression of Fas
      induced by Dex may be one of the mechanism of lymphocytes apoptosis.

PMID- 11326972
TI  - [The growth inhibition of anti-EGF receptor monoclonal antibody to human lung
      adenocarcinoma cells].
AB  - OBJECTIVE: Epidermal growth factor (EGF) and its receptor play a critical role in
      the growth and regulation of many type of malignant cell. The high level of
      expression of the EGFR on normal cell lung cancer(NSCLC) and the important role
      of EGFR in signal transduction make it potentially an excellent target for
      antibody directed therapy. The purpose of this study was to evaluate the anti
      tumor effects of anti-EGFR monoclonal antibody on lung carcinoma cells. METHOD:
      Preparation of hybrid cell producing anti-EGFR monoclonal antibody using EGF
      receptors partially purified from A431 cells as immunogen. The effect of anti
      EGFR monoclonal antibody to human lung cells was investigated in vitro. RESULT:
      The anti-EGFR monoclonal antibody was shown to inhibit the proliferation of human
      lung adenocarcinoma cells in vitro, but no growth-inhibitory effect was observed
      in the human small cell lung cancer cells. The concentration, 15 ug/ml, of anti
      EGFR antibody could inhibit growth rate by 94% and 88% for human lung
      adenocarcinoma cell lines SPC A-1 and A549, respectively. CONCLUSION: Our initial
      results indicate that the anti-EGF receptor monoclonal antibody may be
      potentially useful for the biotherapy of lung adenocarcinoma.

PMID- 11326971
TI  - [Antigen-induced airway leakage in asthmatic guinea-pigs and the effects of BRL
      55834].
AB  - OBJECTIVE: To understand the role of airway leakage in asthma attack and
      investigate the effects of BRL 55834 on prophylaxis and treatment of asthma.
      METHOD: Ten normal and seventeen sensitized guinea-pigs were divided into 5
      groups. After being anesthetized, right carotid artery, right jugular vein and
      trachea were cannulated to monitor systemic blood pressure, inject drugs,
      mechanical ventilate and record airway insufflation pressure (AIP). All animals
      were pretreated with atropine and propranolol (1 mg/kg) 30 min before experiment.
      DMSO or BRL 55834 was administered intravenously 2 min before intravenous
      injection of evans blue (EB, 30 mg/kg), Ovalbumin (OA, 3 mg/ml) was inhaled using
      an ultrasonic nebulier for 30 seconds 1 min after injection of EB. RESULT: (1)
      BRL 55834 (8 micrograms/kg) did not inhibit airway leakage in normal guinea-pig;
      (2) Airway leakage increased in sensitized guinea-pigs significantly after
      inhaling OA, 87 +/- 19 ng dye/mg tissue vs 53 +/- 7 ng dye/mg tissue in trachea
      (Tr); 119 +/- 67 ng dye/mg tissue vs 79 +/- 46 ng dye/mg tissue in main bronchus
      (MB); 65 +/- 44 ng dye/mg tissue vs 46 +/- 17 ng dye/mg tissue in central
      pulmonary airway (CiPA) and 50 +/- 31 ng dye/mg tissue vs 32 +/- 4 ng dye/mg
      tissue in peripheral pulmonary airway (PiPA, P < 0.05). (3) BRL 55834 inhibited
      airway leakage contrast to DMSO, especially in CiPA and PiPA, with an inhibition
      of 48% (Tr, P < 0.05), 57% (MB, P < 0.01), 44% (CiPA, P < 0.05), and 46% (PiPA, P
      < 0.05) after injection of BRL 55834 8 micrograms/kg, and 46% (Tr, P < 0.05), 57%
      (MB, P < 0.01), 56%(CiPA, P < 0.01) and 55% (PiPA, P < 0.01) after injection of
      BRL 55834 16 micrograms/kg, respectively. (4) BRL 55834 decreased base AIP in all
      groups, and inhibited OA-induced AIP increasing in sensitized guinea-pigs, with
      an inhibition of 49% (BRL 55834 8 micrograms/kg) and 57% (BRL 55834 16
      micrograms/kg) in contrast to DMSO. BRL 55834 had a little side-effect on
      cardiovascular system, but without statistical significance. CONCLUSION: Airway
      leakage is one of the most important components in asthma attack, BRL 55834, a
      selective potassium channel activator, not only decreases airway leakage, but
      also inhibits OA-induced increase in airway resistance. All these are beneficial
      to prophylaxis and treatment of asthma.

PMID- 11326973
TI  - [Detection of oncogenic mutations in sputum and its diagnostic value of lung
      cancer].
AB  - OBJECTIVE: To find a new method to molecular biological detection of lung cancer.
      METHOD: The sputum specimens from 96 cases of lung cancer and other lung patients
      were detected for K-ras and p53 mutations by using polymerase chain reaction(PCR)
      and restriction fragment length polymorphism and and immunohistochemistry (IHC)
      techniques. RESULT: 38 out of 62 sputum specimens of lung cancer patients were
      positive for cytology: Sensitivity was 61%. NPV (negative predictive value) was
      59%; p53 was overexpressed in 48 cases: Sensitivity was 77%. NPV was 66%; k-ras
      was positive in 21 cases: Sensitivity was 34%, NPV 42%; The combination of
      conventional cytology and molecular screening(k-ras + p53) produced a sensitivity
      value of 92%(P < 0.05) with an NPV of 84%(P < 0.05); In 24 cases of patients
      whose cytology of sputum was false negative, 17 were found either p53 or k-ras
      positive of which 7 patients were identified to be lung cancer in the follow-up
      study. CONCLUSION: These results suggest that detection of oncogene mutation in
      sputum enhanced and added to the diagnostic value of conventional cytology. It is
      a promising approach to early lung cancer detection and massive screening in
      terms of its rapidity, economy and simplicity.

PMID- 11326974
TI  - [Clinical uses of nitric oxide in pulmonary hypertension].

PMID- 11326975
TI  - [Eosinophil apoptosis and airway inflammation in asthma].

PMID- 11326976
TI  - [Study on the determination of trace metals in complex matrices by chelation ion
      chromatography].
AB  - In this paper, a new method for determination of trace metal ions in complex
      matrices by chelation ion chromatography has been developed. In accordance to
      different analysis purpose, different interference should be selectively
      eliminated. On the chelating resins, all anions, alkali and alkaline earth metals
      could be eluted by ammonium acetate eluent (pH 5.5), tervalent cations could be
      eluted by pyrophosphoric acid/ammonium acetate eluent (pH 5.5). On sulfonated
      cation exchanger, heavy metals, transition metals, iron and aluminum could be
      eluted by hydrochloric acid/ethanol and oxalic acid/nitric acid eluents. Then,
      the concentrated lanthanides and transition metals (Pb, Cu, Cd, Ni, Zn and Co)
      were separated on bifunctional ion-exchange ion-exchange column by a proper
      concentration gradient of eluents, coupled with post-column spectrophotometric
      detection. Test samples could be injected directly into the column for analysis
      after the sample digestion. The detection limits of the method (signal-to-noise =
      3:1) were at or below microgram/L level. The method has been systematically
      applied in rock, alloy, soil, plant and animal samples.

PMID- 11326977
TI  - [Retention behaviours of neutral solutes in reversed-phase capillary
      electrochromatography].
AB  - In this paper, retention behaviours of neutral solutes in reversed-phase
      capillary electrochromatography (RP-CEC) was studied separately with methanol,
      acetonitrile, isopropanol and tetrahydrofuran as organic modifiers. It was found
      that at certain concentration, the order of mu eo was in accordance with the
      epsilon/eta value of the organic modifier in the mobile phase. In addition, the
      relationship between mu eo and phi was relevant to the property of the organic
      modifier. With more organic modifier in the mobile phase, mu eo increased in
      methanol-water and acetonitrile-water systems; it changed little in
      tetrahydrofuran-water system and decreased slightly in isopropanol-water system.
      Linear relationship between capacity factors of neutral solutes and the volume
      fraction of the organic modifier in the mobile phase was obtained in CEC, and was
      similar to that in RP-HPLC. With the same column under the same conditions, it
      was found that the capacity factors of solutes in RP-CEC and RP-HPLC were almost
      the same, which means that the retention mechanisms of neutral solutes in these
      two modes might be quite similar.

PMID- 11326978
TI  - [Study on the retention behaviour and mechanism of organic acids on an anion
      exchanger].
AB  - The retention behaviour and mechanism of organic acids on an anion exchange
      column Shim-pack IC-A1 (Shimadzu, Japan) have been studied. The retention
      valences (x) of organic acids on the anion exchanger were measured based on the
      following equation: logk' = -(x/y)log[Eluent] + constant By using the linearity
      of logk' vs log[Eluent] and the retention valences, the retention mechanisms of
      organic acids can be predicted. Acetic acid eluted as the non-dissociated form by
      a non ion exchange mechanism, because its retention valence was only 0.21. In
      this work, the multi-peak for one organic acid was observed. The chromatograms of
      citric acid obtained using PyA eluent with different concentration were showed.
      Two peaks were observed. As eluent concentration decreased, the detection
      sensitivity (peak area) was increased due to the decrease of the background
      conductivity. The multiple peaks of citric acid were also observed when the
      mixture of phthalic acid(PhA) and trihydroxymethylaminomethane (TRIS) was used as
      eluent. The multi-peaks for one organic acid result from the fact that different
      forms of the organic acid can be separated each other on anion exchanger by ion
      exchange mechanism. The two peaks of citric acid were caused by separation of
      mono- and divalent citrate anion.

PMID- 11326979
TI  - [Preparation and evaluation of C60 bonded silica phase for high performance
      liquid chromatography].
AB  - C60 was chemically attached to gamma-(ethylenediamino) propylsilyl-bonded silica
      as a stationary phase for liquid chromatography. The new stationary phase was
      used to investigate the separations of polycyclic aromatic hydrocarbons (PAHs)
      and tert-butylcalix[n]arenes. The elution order of PAHs was found to be similar
      to that on octadecylsilica (ODS); the elution order of tert-butylcalix[n]arenes
      was found to be tert-butylcalix[8]arene, tert-butylcalix[4]arene and tert
      butylcalix[6]arene with 1%(V/V) isopropanol/cyclohexane as a mobile phase.

PMID- 11326980
TI  - [Chiral ion-pair chromatography].
AB  - A chiral counter-ion dissolved in the mobile phase can be used to separate
      enantiomers of acids and amines. The principles and related separation variables
      have been reviewed. A successful enantiomeric separation is highly dependent on
      the features of counter-ion chosen for the experiments. The most important
      properties of a suitable chiral reagent can be summarized as follows: (1) acid
      base character of counter-ion; (2) hydrophobicity of counter-ions; (3) presence
      of suitable functional groups; (4) enantiomeric purity of counter-ion, etc. It is
      also discussed about the influences of various chromatographic conditions and the
      applications of chiral ion-pair chromatography.

PMID- 11326981
TI  - [Determination of the soluble non-starch polysaccharides in rice and wheat bran
      by gas chromatography].
AB  - Cereal polysaccharides can be broadly classified into two distinct and chemically
      well-defined types. They are the storage polysaccharides (alpha-glucan) and the
      structural polysaccharides starch (beta-glucan) which are usually called non
      starch polysaccharides (NSP). The determination of soluble non-starch
      polysaccharides in rice and wheat bran by gas chromatography has been developed.
      The free sugars in the sample were extracted with 80% ethanol. The residue was
      hydrolyzed in an acetic acid buffer solution (pH 5.0) in the presence of amylase
      and amyloglucosidase to remove starch. The soluble NSP obtained was further
      hydrolyzed in the acidic condition to produce the corresponding monosaccharides
      which were derivatized to form alditol acetates for GC analysis with allose as
      the internal standard. The GC conditions were OV-1701 column (25 m x 0.3 mm) with
      temperature program from 195 degrees C to 225 degrees C and FID.

PMID- 11326983
TI  - [Rapid determination of creatinine in urine by capillary electrophoresis in a
      multiple injection mode].
AB  - The level of urinary creatinine in clinic diagnosis is one of the useful index of
      renal function, and is often used as a reference of some biochemical substance
      determined in random urine. In this paper, a rapid multiple-injection capillary
      electrophoresis(CE) method for the determination of urinary creatinine is
      reported. A 36 cm x 50 microns coated capillary, a phosphoric acid buffer(0.1
      mol/L, pH 2.5)and UV-detector at 200 nm wavelength were used in this method. In
      comparing with single injection for five samples, the analysis time of five
      successive injections can save 20 min. By use of pyridine as internal standard,
      the correlation between the concentrations of creatinine and the corresponding
      peak height ratios of creatinine and pyridine is good(r = 0.9996), and the assay
      precision is acceptable. We also compared the CE method with the bio
      analyser(Jeffe' kinetic), and the results showed a satisfactory correlation (r =
      0.9773, n = 12) and a shorter analysis time.

PMID- 11326982
TI  - [Simultaneous determination of creatinine, pseudouridine and uric acid in serum
      and urine by high performance liquid chromatography].
AB  - In this paper a sensitive, rapid and simple HPLC method for the simultaneous
      determination of creatinine (Cr), pseudouridine (Pu) and uric acid(UA) has been
      established. We have evaluated clinical value of the method in the early
      diagnosis of diabetic nephropathy (DN). Separation was obtained using Shim-pack
      CLC-ODS 15 x 0.6 cm column and mobile phase of buffer solution of phosphate (pH
      3.0, 0.02 mol/L) with flow rate of 1 mL/min. Detection was performed with UV
      detector at an automatic adjustment of wavelength. The recoveries of Cr, Pu and
      UA were 101.4%, 104.9% and 105.0% respectively. The calibration curves were
      linear within the concentration range of 8.6-274.6 mumol/L for Cr, 0.72-22.93
      mumol/L for Pu and 19.1-612.7 mumol/L for UA (n = 6, r > 0.999, p < 0.01). The CV
      for within day and between day measurements were < 2.5% and < 5.0% respectively.
      In addition, Pu, Cr and UA were simultaneously determined in serum and urine of
      39 patients with diabetic mellitus (DM). 15 patients with nephrotic syndrome (NS)
      and 53 normal subjects by the method. Results include: 1. the levels of serum Pu
      in all DM patients (100%) with microalbuminuria (MiAU) and macroalbuminuria
      (MaAU) were greater than maximum of normal subjects (X + 2S). In addition, in 9
      DM patients (41%) with normal albuminuria (NAU) the levels were also greater than
      the maximum. 2. In patients with DM, there was no correlation between the serum
      Pu and the urinary albumin excretion (UAE), whereas the serum Pu correlated
      closely with the serum Cr. However, the incidence for serum Pu increase was
      significantly greater in patients. 3. The levels of serum Pu in patients with NS
      were greater than those in control subjects and patients with DM. Conclusion is
      that the determination of serum Pu could be used as sensitivity index for the
      early diagnosis of DN.

PMID- 11326984
TI  - [Determination of hydrophobic pharmaceutical: tablet of reserpine compound by
      capillary zone electrophoresis].
AB  - Tablet reserpine compound is a kind of hydrophobic pharmaceutical that can not be
      separated by CZE with salt-water system. We solved this problem by adding organic
      component into the buffer. Thus a satisfactory separation of reserpine and
      hydrochlorothiazide was achieved by using a 24% (V/V) acetonitrile in the buffer
      solution of 10 mmol/L phosphate with a pH 9.0. The capillary column of 50 microns
      i.d. and 50 cm total length with effective length(the distance from the inlet to
      the detector) of 35 cm was used during all analytical procedure. The factors
      which influenced resolution such as the pH, acetonitrile content and phosphate
      concentration have been investigated. The CZE separation conditions of reserpine
      and hydrochlorothiazide using the standard mixture solution, are also showed. In
      the quantitative analysis, the reproducibility of CZE determination is
      illustrated. The regression coefficients of calibration graphs and the detection
      limits are given. The results of the study of recovery and quantitative results
      of these components using external standard method are given.

PMID- 11326985
TI  - [A reversed-phase high performance liquid chromatographic method for the
      determination of pinoresinol diglucopyranoside in Eucommia Ulmoides Oliv].
AB  - A reversed-phase high performance liquid chromatographic method for the
      determination of (+)-pinoresinol-di-O-beta-D-glucopyranoside in the bark of
      Eucommia Ulmoides was established. The air-dried bark of E. Ulmoides was ground
      into powder and extracted continuously with methanol. The extract was evaporated
      under reduced pressure, then suspended in water. This suspension being subjected
      to column chromatography was eluted successively with water, 30%, 50% and 90%
      aqueous solution of ethanol. The 30% EtOH eluate was concentrated and then
      injected into HPLC system. The conditions of HPLC were: YWG-C18 column (250 mm x
      4.6 mm i.d. 10 microns); 28%(V/V) methanol mobile phase and UV detector at 232
      nm. The calibration curve was linear in the range of 0.068 microgram-0.68
      microgram of(+)-pinoresinol-di-O-beta-D-glucopyranoside with correlation
      coefficient of 0.9999. The coefficient of variation and average recovery were
      0.50%-0.74% (n = 5) and 99.22% (n = 3) respectively.

PMID- 11326986
TI  - [Analysis of paracetamol, caffeine and chlorphenamine maleate in suxiaoshangfeng
      capsules by capillary gas chromatography].
AB  - A simple and rapid method for simultaneous determination of paracetamol, caffeine
      and chlorphenamine maleate in Suxiaoshangfeng capsule by capillary gas
      chromatography with n-hexadecane as internal standard has been reported. In the
      capsule, the three components can be separated on a 5% Ph-Me-Silicone column
      (2.65 microns x 0.53 mm x 10 m), with programmed column temperature from 180
      degrees C to 230 degrees C at 8 degrees C/min, hold 6 min and then 230 degrees C
      to 260 degrees C at 10 degrees C/min, hold 10 min. Both the injector and FID
      detetor temperatures were 280 degrees C. N2 flow rate was 3.5 mL/min and H2 35
      mL/min. The injection volume was 1 uL with splitting ratio of 1/25. These
      components were identified by their retention times and quantitatively determined
      by their peak areas. The calibration curves were, r = 0.9996 for paracetamol, r =
      0.9984 for caffeine and r = 0.9996 for chlorphenamine maleate. The linear ranges
      were 4.0-20 g/L, 0.15-0.75 g/L and 0.080-0.40 g/L, respectively. The average
      recoveries were 99.62% (RSD = 0.40%, n = 5), 96.46%. (RSD = 1.32%, n = 5) and
      98.55% (RSD = 0.65%, n = 5), respectively.

PMID- 11326989
TI  - [High performance liquid chromatographic analysis of monosaccharide composition
      in lacquer polysaccharide from sap of lac tree].
AB  - This paper reports the separation and determination of monosaccharide composition
      in lacquer polysaccharide (LPS) by HPLC. The five monosaccharides were analyzed
      on microBondapak NH2 column (300 mm x 7.8 mm i.d. 10 microns) and refractive
      index detection. The mobile phase was CH3CN-H2O-CH3OH (70:25:5, V/V) flowing at a
      rate of 1.6 mL/min. These monosaccharides were identified by their retention
      times and quantitatively determined by their peak areas. LPS samples were
      hydrolysed with 2.0 mol/L CF3COOH. The linear correlation coefficients were all
      over 0.9953. The average recoveries of monosaccharides ranged 98.8%-103.6% and
      relative standard deviations were below 5%. The method is simple, rapid, precise,
      and has been used satisfactorilly for analysis of the monosaccharides hydrolyzed
      from LPS, which were isolated from sap of three kinds of Lac tree (Maoba Damu,
      Maoba Xiaomu and Jianshi) in Hubei province.

PMID- 11326988
TI  - [Analysis of the major components in cannabis by capillary gas chromatography].
AB  - A capillary GC method for the simultaneous determination of cannabidiol (CBD),
      tetrahydrocannabinol (THC), and cannabinol (CBN) in cannabis is described. The
      major components in cannabis were extracted with chloroform. After being
      concentrated by evaporation, the residue was dissolved in methanol. The resulting
      solution was used for analysis. The conditions for determination were: FID
      detector, HP-5 capillary column, 10 m x 0.53 mm x 2.65 microns film, column
      temperature 220 degrees C. The recoveries of the three major components were
      97.3%-104.0%(CBD), 97.3%-106.6%(THC) and 95.3%-102.4% (CBN). The coefficients of
      variation are less than 3%. The limit of detection for the three components was
      0.2 mg/L, and their linearity was in the range of 20-120 mg/L. Identification of
      each component was achieved by comparison of retention times with the standards.
      This method has the advantages of simplicity, rapidity, sensitivity and accuracy.

PMID- 11326987
TI  - [Quantitative determination of extracellular glutathione and cysteine in gerbil
      brain by microdialysis and high performance liquid chromatography with
      electrochemical detection].
AB  - A method for the determination of glutathione and cysteine in microdialysate by
      HPLC with electrochemical detector has been described. The column used was
      Hypersil ODS, 5 microns, 200 mm x 4.6 mm i.d. and mobile phase was 50% 0.2 mol/L
      KCl, 10.6% 0.2 mol/L HCl, 39.4% methanol and 0.1 mmol/L EDTA (pH 2.0) with a flow
      rate of 1 mL/min. The microdialysis probe (membrane: pc, length: 10 mm, diameter:
      0.5 mm/CMA) was inserted into the right striatum of gerbil at the following
      coordinates: 1.5 mm anterior and 1.5 mm lateral to bregma, and 3.5 mm below dura.
      Electrochemical pretreatment of a glassy carbon electrode used as a working
      electrode in an electrochemical detector has been found to enhance the analytical
      capability of detector for the determination of glutathione and cysteine. The
      quantitative determination was made with an electrochemical detector at 0.9 V and
      by external standard method. The method gave good recoveries and
      reproducibilities. The average recoveries of two analytes were 91.4% and 87.3%
      respectively. Extracellular fluid glutathione and cysteine concentrations in the
      striatum of gerbil brain were determined by the microdialysis and chromatography
      described in this study. The contents of Cys and GSH in microdialysate of gerbil
      striatum were 65.54 +/- 12.96 nmol/L and 68.59 +/- 13.23 nmol/L. The results were
      comparable with those reported in previous works.

PMID- 11326990
TI  - [Determination of uric acid, creatinine and pseudouridine in human urine by high
      performance capillary zone electrophoresis].
AB  - A simultaneous determination of uric acid, creatinine and pseudouridine in human
      urine by high performance capillary zone electrophoresis(HPCZE) is described. The
      urine samples were refrigerated and filtered. Then the samples were directly
      introduced into the capillary and a phosphate buffer solution(pH 6.1) was
      employed. The capillary used was 36 cm x 50 microns i.d. and detection was
      carried out with a UV monitor at 210 nm. The calibration curve showed a good
      linearity for uric acid, creatinine, and pseudouridine in the concentration range
      of 2-80 mg/L and their correlation coefficients were 0.996, 0.996 and 0.999
      respectively. Within day CV for assaying the urine samples of uric acid,
      creatinine and pseudouridine were 5.0%, 3.0%, and 4.4%, and the corresponding
      between day data were 6.5%, 5.9%, and 5.3%, respectively. The recoveries of uric
      acid, creatinine and pseudouridine were 99.0%, 102.%, 92.2%, respectively. The
      total time for separation and determination was within 10 min. This method is
      characterized by direct assay of urine samples without any pretreatment. The
      results show that HPCZE is a simple, rapid, sensitive and reliable assay method.

PMID- 11326992
TI  - [Determination of antimicrobial preservative dimethyl fumarate by high
      performance liquid chromatography].
AB  - This paper described a HPLC method for determining dimethyl fumarate (DMF), a new
      antimicrobial preservative. Chromatographic conditions were as follows: Micropak
      MGH 5 mu cap column, 4.00 mm x 300.0 mm EtOH-H2O (90:10, V/V) eluent, and UV
      detector at 216 nm. In the range of 0.036-2.96 micrograms, the sample size and
      peak area showed a linear relationship with regression equation, Y = 3.215 x 10(
      6)X - 0.04797 and r = 0.9996. Standard deviation was 3.2 x 10(-4).

PMID- 11326991
TI  - [Determination of 10-hydroxy-2-decenoic acid (10-HDA) in Chinese traditional
      medicine preparations by high performance liquid chromatography].
AB  - This paper reports the quantitative determination of 10-HDA in Chinese
      traditional medicine preparations by HPLC. Spherisorb C18 column was used. The
      mobile phase consisted of methanol-distilled water and phosphoric acid(45:55:0.5,
      V/V). The elute was monitored at 210 nm. The good linearity was shown between the
      concentration of 10-HDA and peak area in the concentration range of 6.0-30.0 mg/L
      (r = 0.9999, n = 5). The detection limit was 0.2 mg/L (S:N = 3:1). The within-day
      and between-day RSD were 2.1%-2.2% and 2.9%-4.0%, respectively. Peaks of 10-HDA
      and impurities in these samples were separated completely. This method is simple,
      sensitive and accurate.

PMID- 11326993
TI  - [An improved method of cholesterol determination in egg yolk by high performance
      liquid chromatography].
AB  - An improved method for cholesterol determination in egg yolk is reported in this
      paper. Egg yolk was first diluted. Cholesterol was then extracted with ethyl
      ether and petroleum ether, and quantified by reversed phase liquid chromatography
      on a Zorbax ODS column (0.46 mm x 15 cm, 5-6 microns) using a mobile phase of
      acetonitrile and 2-propanol (4:1) with a flow rate of 0.6 mL/min. A linear
      correlation was observed between 0.05-0.40 g/L of cholesterol. The determination
      limit was 0.02 g/L. This proposed method of HPLC determination of egg yolk
      without saponification is superior to colorimetric determination on the sample
      with saponification, and comparable to HPLC determination with saponification of
      the egg yolk sample in terms of reliability. No difference in final results was
      observed between egg yolk sample with saponification and the same sample without
      saponification. Rapid and reproducible quantification of cholesterol in egg yolk
      can be completed with this new method. Omission of saponification has made this
      proposed method more convenient than those ever reported, and can be used in yolk
      cholesterol study with greater ease.

PMID- 11326994
TI  - [The relationship between chromatographic retention value and grey model
      parameters].
AB  - The relationship between development parameter a, grey action variable u in the
      grey model GM(1,1) and parameters A,B which express the relation of k' and phi,
      that is, 1nk' = A + B phi have been studied. The functions of these two kinds of
      parameters which are a = -B lambda and u = B lambda eA[(1 - e-B lambda)(-1) - 1]
      are given. Therefore, it can predict the position of peaks and the possibility of
      separating the components in different mixtures. It verifies the experimental
      data, and gives out a proper method to amend equations. The results show that the
      function is fit for not only the research of chromatographic parameters of
      explosives but also the prediction of A,B values of other compounds.

PMID- 11326995
TI  - [Preparation of novel macroporous silica-based amide-polymer-bonded packing and
      its application to the separation of proteins].
AB  - A novel macroporous silica-based amide-polymer-bonded packing for protein
      separations in HPLC is described. The macroporous silica support was bonded with
      diethoxymethyl vinyl silane and then copolymerized with methylacrylamide and
      divinylbenzene to produce a tailored stationary phase with high resolution and
      inertness. The repeatability of packing preparation is good. They were
      characterized through the application of a standard protein mixture of pepsin,
      glucose oxidase, bean trypsinogen inhibitor and ribonuclease. The time for
      elution of these proteins is less than 12 minutes. It is suggested that the
      macroporous silica-based amide-polymer-bonded packing can be used to quickly
      separate biopolymer. This packing is a better alternative for the biopolymer
      separation.

PMID- 11326996
TI  - [Determination of HIgG in Human plasma by high performance membrane affinity
      chromatography(HPMAC)].
AB  - An assay technique for determination of Human IgG in human plasma has been
      developed by utilizing Protein A bound to the modified cellulose matrices based
      on the strong affinity between protein A and Fc region of IgG. The pH values of
      loading buffer and elution buffer were 7.0 and 2.3 respectively. The cartridge
      used was 20 mm x 4 mm i.d. and detection was carried out with a UV monitor at 280
      nm. The non-specific adsorption of two kinds of media has been studied. The media
      without hexyldiamine arm gives very low non-specific adsorption BSA. The
      calibration curve showed a good linearity (correlation coefficient > 0.9992) in
      the injected amount range of 9-70 micrograms for HIgG. The total time for
      separation and determination was within 5 min and the total time of rapid assay
      was within 30 s. Relative standard deviations of peak areas were 1.5% (n = 5) and
      3.6% (n = 3) for HIgG in standard solution and human plasma respectively.

PMID- 11326999
TI  - [Determination of sunscreen agents in cosmetic products by reversed-phase high
      performance liquid chromatography].
AB  - A method for quantitative determination of eleven sunscreen agents (benzophenone
      4,p-amino-benzoic acid, salicylic acid, benzophenone-3,phenyl salicylate, 4
      methylbenzylidene camphor, octyl dimethyl p-amino-benzoate, isopropyl
      dibenzoylmethane, butyl methoxydibenzoylmethane, octyl methoxycinnamate, octyl
      salicylate) in cosmetic products is described. It was based on a high performance
      liquid chromatographic separation under the condition of isocratic elution with a
      mixture solution of methanol-THF-water-70% perchloric acid (200:200:160:0.1) by
      using a column packed with 10 microns YWG-C15 and UV detection. The recoveries (n
      = 6) were 94.1%-101% and the relative standard deviations(n = 6) for all eleven
      sunscreen agents were less than 5%. In addition, the results of analysis of 30
      samples out of 103 samples of commercial suntan cosmetics performed are reported
      in this paper.

PMID- 11326998
TI  - [Study of protein separation by reversed-phase high performance liquid
      chromatography].
AB  - Reversed-phase high performance liquid chromatography (RP-HPLC) of protein on
      large pore silica (20-30 nm) n-alkyl-bonded(C4 and C5) phase columns was studied
      using a trifluoroacetic acid (TFA)/2-propanol mobile phase system. The influence
      of concentration of organic modifier (2-propanol) and ion-pairing acid (TFA) on
      the protein retention time was examined. The results showed that the plot of the
      retention time vs-2-propanol concentration in mobile phase was U-shaped. The
      mechanism of protein in reversed-phase high performance liquid chromatography is
      also discussed.

PMID- 11327000
TI  - [Determination of hyperin in Sanguisorba Officinalis L. by high performance
      liquid chromatography].
AB  - An HPLC method for the determination of hyperin in Sanguisorba officinalis L. was
      investigated. 0.5 g of dried powdered crude drug was weighed accurately in a 50
      mL volumetric flask added with 40 mL methanol, supersonicated for 30 min and then
      made up to volume with methanol. The sample solution was separated on a Shim-pack
      ODS column(6.0 mm i.d. x 150 mm, 5 microns) with methanol-0.025 mol/L phosphoric
      acid (adjusted to pH 3.0 by using triethylamine)(50:50) as the mobile phase and
      detected at UV-370 nm. Calibration curve of hyperin was obtained for the
      concentration range of 0.046-0.2 microgram. The corresponding regression equation
      was Y = 154 x 10(4) X-0.28 x 10(4), r = 0.9998. The recovery was 98.7% and
      relative standard deviation was 1.9%. The results showed that this method is
      simple, specific and accurate.

PMID- 11326997
TI  - [Application of capillary electrophoresis on environmental analysis].
AB  - A review of applications of capillary electrophoresis (CE) on environmental
      analysis is presented, based mainly on the worldwide published works in the
      latest years. The current achievements and application potential of CE in the
      field of environmental analysis are included with 58 references.

PMID- 11327001
TI  - [Determination of morphine in compound liquorice tablets by high performance
      liquid chromatography with SEP-PAK C18 cartridge pretreatment].
AB  - An efficient method combining SEP-PAK C18 cartridge solid phase extraction (SPE)
      with reversed-phase high performance liquid chromatography for the quantitation
      of morphine in the Compound Liquorice Tablet is presented. The tablets have been
      used for making expectoration easy and relieving cough for years. The tablet
      powder (approximately 1 tablet) was added into a stoppered centrifuge tube, and
      vertically extracted with 5 mL of 0.5% HAc for 5 min. After centrifugation the
      supernatant was transferred to a beaker and the extraction was repeated twice
      with 4 mL and then 3 mL of 0.5% HAc. Five millilitres of carbonate buffer (pH
      8.9) was added to the combined extracts. A SEP-PAK C18 cartridge was pretreated
      by passing methanol and distilled water, using a glass syringe. The mixture was
      applied on it and allowed to flow through. The cartridge was washed first with 5
      mL of 10% methanol solution and then the morphine was eluted with 4 mL of 70%
      methanol solution into a 5 mL volumetric flask and was finally diluted to volume
      with 70% methanol solution. Analysis was performed on a mu-Bondapak C18
      column(300 mm x 4.6 mm i.d., 10 microns) with 0.1 mol/L NaH2PO4-methanol(5:1) as
      the mobile phase and detection at 286 nm. The average recovery of morphine was
      (101.2 +/- 1.5)% and RSD was 1.5%. The method is simple, rapid, accurate, and
      reproducible, and can be used in drug control.

PMID- 11327002
TI  - [Determination of organic pollutants in water by off-line supercritical fluid
      extraction-Gas Chromatography/Infrared Spectrometry/Mass Spectrometry].
AB  - A supercritical fluid extraction (SFE) method using carbon dioxide for the
      determination of organic pollutants in Yellow River water was developed. In this
      paper, organic contaminants in 3 L Yellow River water were concentrated on 1 g
      GDX-301 adsorbent and then eluted from the adsorbent with supercritical CO2. The
      analytes extracted by SFE were collected into 1 mL alcohol collecting solvent
      through a SiO2 restrictor (35 cm x 50 microns i.d.). Finally, the collecting
      solvent was analyzed by Gas Chromatography/Infrared Spectrometry/Mass
      Spectrometry. The SFE conditions which were optimized for removal of the analytes
      from adsorbent were 20 MPa, 60 degrees C and 40 min. The extraction efficiencies
      of SFE were directly compared to those obtained by using 15 mL dichloromethane
      elution. Efficiencies of SFE under conditions of 20 MPa, 60 degrees C and 40 min
      were generally higher than those of solvent elution.

PMID- 11327003
TI  - [Determination of dioxane in alkyl alcohol polyoxyethylene ether].
AB  - In this paper, dioxane in alkyl alcohol polyoxyethylene ether has been determined
      by headspace gas chromatography. The standard curve and headspace detection
      conditions are given. Correlation coefficient is 0.9989. The recoveries of
      dioxane ranged from 91.6% to 97.6%. The relative standard deviations were less
      than 2.5%. The limit of determination was 20 micrograms/L. The method is simple,
      fast and accurate with higher sensitivity, less interference and better
      reproducibility.

PMID- 11327004
TI  - [Determination of Ondansetron in injection by high performance capillary zone
      electrophoresis].
AB  - Ondansetron is a kind of drug which is used for the treatment of nausea and
      vomiting induced by cytotoxic chemotherapy and radiotherapy. In this paper, a
      method to determine Ondansetron in injection by high performance capillary zone
      electrophoresis is discussed. The injection was directly introduced into the
      capillary employing 40 mmol/L phosphate at pH 4.03 as buffer. The capillary used
      was 75 microns in i.d. and 47 cm in length. UV detection was set at 254 nm. The
      calibration curve showed good linearity. The recovery of Ondansetron ranged from
      95%-98% with a coefficient of variation of 1.05%(n = 4). This method is simple,
      rapid and reliable.

PMID- 11327005
TI  - [Separation and determination of naproxen by reversed-phase high performance
      liquid chromatography].
AB  - A reversed-phase HPLC method has been developed for the separation and
      determination of naproxen and its bromo-substituted compound. These compounds
      were separated on a Shim-pack CLC ODS column (5 microns, 250 mm x 4.6 mm i.d.) by
      using a methanol-water (80/20, V/V) solution containing 50 mmol/L lactic acid and
      adjusted to pH 2.5 with perchloric acid as mobile phase, with flow rate of 0.8
      mL/min and UV detection at 271 nm. Benzoic acid was selected as an internal
      standard. At the concentration range of 5-100 mg/L, the linear internal standard
      working curves with r > 0.9995 were obtained. The accuracy of this method for
      naproxen and its bromo-substituted compound were 99.83%-102.07% and 99.00%
      100.83%, and RSD were < 2.58% and < 3.64% respectively.

PMID- 11327008
TI  - [Purification of recombinant erythropoietin by reversed-phase high performance
      liquid chromatography (RP-HPLC)].
AB  - Recombinant erythropoietin is a glycoprotein which is strongly hydrophobic. We
      purified recombinant erythropoietin by RP-HPLC. The results showed that 30 nm
      Spherisorb C4 reversed-phase column and acetonitrile-TFA mobile phase with
      gradient elution, could readily isolate recombinant erythropoietin from crude
      samples with high speed and efficiency. Erythropoietin could be eluted at the
      concentration of about 50% acetonitrile with appropriate sample purity and
      elution gradient. When RP-HPLC is used as a final step of purification, the
      purity of sample should be at least 60%. The purity of the product tested by SDS
      PAGE was nearly 100%. And the specific activity of the product was about 1.96 x
      10(3) IU/g protein.

PMID- 11327007
TI  - [Isolation and purification of the active principle from agkistrodon acutus snake
      venom by high performance ion-exchange liquid chromatography].
AB  - The active component from Agkistrodon acutus snake venom was further purified by
      high performance ion-exchange liquid chromatography over a Protein-PAK DEAE-8HR
      column(10.0 mm i.d. x 100 mm). The elution was operated with a linear gradient
      from 10% to 100% NaCl-0.02 mol/L Tris-HCl buffer(pH 8.0). The quantitative
      results were calculated as 45.41% based on peak area nomalization and the purity
      of the active component was 90% determined by electrophoresis.

PMID- 11327006
TI  - [Determination of enrofloxacin and it's main metabolite in animal plasma by
      reversed-phase ion-pair high performance liquid chromatography].
AB  - This paper describes a method for determining enrofloxacin (ERFX) and it's main
      metabolite ciprofloxacin(CPFX), in animal plasma by RP-IPLC simultaneously.
      Dichloromethane was utilized as an extracting agent of plasma. Chromatographic
      conditions were ODS column with methanol-25 mmol/L tetrabutylammonium hydroxide
      (20:80, V/V, pH 3.0) as mobile phase, pipemidic acid as the internal standard and
      UV detection at 272 nm. With the method established in this paper, the work is
      done simply, rapidly, sensitively and accurately. It was actually adapted to
      determine ERFX and it's metabolite CPFX concentrations in plasma and
      pharmacokinetic studies, and to determine ERFX and CPFX contents in calves plasma
      successfully for the first time.

PMID- 11327009
TI  - [Separation of norephedrine enantiomers by high performance liquid chromatography
      (HPLC) with urea derivative as chiral stationary phase].
AB  - By using normal-phase HPLC with urea derivative as chiral stationary phase(CSP),
      the direct separation of racemic norephedrine has been investigated. The
      resolution was optimized by varying the concentration of iso-propanol in a
      ternary mobile phase which consists of two other components: hexane and 1,2
      dichloroethane. The lower the percent of iso-propanol, the better the resolution
      is. But the retention time is longer as the percent of iso-propanol decreases. In
      an attempt to reduce the retention time without reducing the stereoselectivity,
      we chose the mixture of hexane, 1,2-dichloroethane and iso-propanol as the mobile
      phase with a proportion of 73.5:25:1.5 in vol. We also altered the organic
      modifier by substituting ethanol, acetonitrile and tetrahydrofuran (THF) for iso
      propanol. The addition of ethanol appears to increase the hydrogen bond
      interactions between the solute and solvent, which results in lower k' values and
      an increase in alpha and Ra. Acetonitrile is only a kind of proton-accepter and
      the interactions of hydrogen bonding between the solute and solvent are weaker
      than iso-propanol, which results in higher k' values and a reduction in alpha and
      Ra. These separations are in agreement with the three-point rule. When THF is
      used as organic modifier, a reversed elution order and a more favorable
      separation can be obtained. The specific behavior of THF in HPLC has not been
      explained satisfactorily yet.

PMID- 11327010
TI  - [Determination of serotonin in rat brain by gas chromatography/mass
      spectrometry].
AB  - A GC/MS method for the determination of serotonin (5-hydroxytryptamine, 5-HT) has
      been developed. 5-HT in homogenized rat brain was acylated and extracted into
      EtOAc. The acylate was further derivatized with heptafluorbutyl anhydride and
      formed a spirocyclic pentafluoropropionyl derivative. Subsequent analysis of 5-HT
      derivative by gas chromatography-electron capture negative ion chemical
      ionization mass spectrometry was highly specific and sensitive. The assay is
      linear from 0.5 to 50 micrograms/L with a linear equation of Y = 0.134 8X -
      0.07995, r = 0.999. The recovery was 98.2% +/- 3.8% (n = 10) and the limit of
      detection was 0.5 microgram/L. The reproducibility of 5-HT determination in rat
      brain was less than 10% (RSD) at both levels of 1.0 microgram/L and 50.0
      micrograms/L. The method has been applied to analysis of 5-HT in the dose rat
      brain successfully.

PMID- 11327011
TI  - [Determination of vitamin D3 in health-care foods fortified with calcium by
      reversed-phase high performance liquid chromatography].
AB  - "Bu Gai Bao" and "Gaoxiao Man Gai" are health-care foods fortified with calcium
      for people of all ages. This paper describes a method of reversed-phase high
      performance liquid chromatography for quantitating vitamin D3 in these products.
      The method is simple, sensitive, and suitable for routine analysis of vitamin D3
      in a variety of health-care foods fortified with calcium. Shimadzu LC-4A high
      performance liquid chromatograph with SPD-2AS UV detector and C-R2AX data
      processor were used. The vitamin D3 in products was extracted with chloroform and
      separated with mu-Bondapak C18 column(300 mm x 3.9 mm i.d.) and methanol
      water(87:13, V/V) mobile phase with detection at UV-264 nm. Regression
      coefficient of correlation of calibration curves in the range of 10-50 mg/L was
      0.9998. Average recoveries of vitamin D3 added to the products was 95.63%. The
      coefficients of variation of vitamin D3 in both products were 0.24%-0.49%.

PMID- 11327012
TI  - [Determination of antioxidants BHT,BHA and PG in food with high performance
      liquid chromatography].
AB  - An accurate and rapid method for simultaneous determination of antioxidants
      butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT) and propyl gallate
      (PG) in food by reversed-phase high performance liquid chromatography was
      established. The sample was extracted with hexane. Being filtrated and dried by
      N2, the residues in evaporator was dissolved in a certain amount of water-C2H5OH
      (1:4, V/V) and filtered with 0.5 micron of filter membrane for HPLC analysis. The
      chromatographic conditions were Radial-PAK C12 column, methanol-water (92:8, V/V)
      mobile phase adjusted to pH = 3 with phosphoric acid and UV-280 nm detector. By
      using external standard method the analytical results showed that the
      coefficients of variation of PG,BHA and BHT were 0.61, 0.08 and 1.44
      respectively, linear correlation coefficients were more than 0.999 and recoveries
      were 92%-98% (n = 6). The lowest detection limit was 0.5 mg/L.

PMID- 11327013
TI  - [The synergistic effect of tetrandrine and rotundine on the action potential of
      rabbit sinus node dominant pacemaker cell and calcium currents of ventricular
      myocytes from guinea-pig].
AB  - Standard microelectrode technique and the whole-cell clamp technique were used to
      investigate the effects of tetrandrine and rotundine on the action potential of
      rabbit sinus node dominant pacemaker cell and calcium currents of ventricular
      myocytes from guinea-pig. The results indicate that: tetrandrine 1-200 mumol.L-1
      and rotundine 3-300 mumol.L-1 decreased the action potential amplitude(APA), the
      maximal upstroke velocity (Vmax), spontaneous depolarizing velocity of phase
      4(SP4) and prolonged the sinus circle length(SCL) in a dose-dependent manner.
      Tetrandrine 0.1 mumol.L-1 in combination with rotundine 0.3 mumol.L-1 was shown
      to effectively reduce the ICa of ventricular myotytes from guinea-pig, the rate
      of inhibition is 19.6%. The results suggest that the two drugs have a good
      synergistic effect on inhibiting calcium current. These results might also put
      forward a valuable theoretic base for using the two drugs together in treating
      patients.

PMID- 11327014
TI  - [Protection of ebselen on oxygen free radical-induced lipid peroxidation damage
      of cultured rat cortical neuron and cortical mitochondria].
AB  - Ebselen (2-phenyl-1, 2-benzisoselenanzol-3 (2H) one, C13 H9NOSe) is a seleno
      organic anti-oxidant compound. In this study, the effect of ebselen on lipid
      peroxidation damage induced by O2.- and .OH in vitro, of cultured rat cortical
      neuron and cortical mitochondria was studied. When neuron was exposed to
      hypoxanthine/xathine oxidase system and vitamin C/CuSO4 system, obvious damage
      was detected: lactic dehydrogenase(LDH) was released and TBARS content increased.
      Ebselen (10, 25, 50 mumol.L-1) reduced LDH efflux induced by O2.- and .OH in a
      dose-dependent manner. As for the TBARS content, from 5 mumol.L-1 to 50 mumol.L
      1, ebselen negated its increase, also dose-dependently. Furthermore, ebselen
      lowered TBARS content of cortical mitochondria treated with O2.- and .OH in a
      dose-related manner. But ebselen showed no activity of scavenging O2.- and .OH.
      This suggests that ebselen has direct anti-oxidant activity on neuron and its
      activity is not achieved by scavenging oxygen free radical.

PMID- 11327016
TI  - [Estimating concentrations of serum total digoxin and digoxin-like immunoreactive
      substances in patients of cardiac failure with renal insufficiency].
AB  - Measurement of serum digoxin concentration is recommended as a routine in
      patients undergoing digoxin therapy because its therapeutic range is narrow. The
      presence of a high concentration of digoxin-like immunoreactive substances(DLIS)
      in human serum have been reported in a number of pathophysiological conditions.
      DLIS which cross-react with anti-digoxin antibodies, can falsely elevate the
      total digoxin concentration and is troublesome in the therapeutic monitoring of
      digoxin. The concentrations of serum total digoxin and DLIS in twelve patients of
      cardiac failure with renal insufficiency were estimated after determination of
      free digoxin by ultrafiltration with fluorescence polarization immunoassay. In
      these patients, the free digoxin concentration in serum determined was 0.79 +/-
      0.48 (0.46-2.10) nmol.L-1. The total digoxin determined(1.31 +/- 0.80 nmol.L-1)
      was significantly higher than the calculated total digoxin(1.05 +/- 0.64 nmol.L
      1) (P < 0.01), suggesting the presence of elevated DLIS in serum for these
      patients. The calculated DLIS concentration was 0.27 +/- 0.19(0.07-0.76) nmol.L
      1. The results were well consistent with that obtained by recently published
      method of Dasgupta et al. In conclusion, the approach presented in this paper can
      estimate the true serum concentrations of digoxin and DLIS in patients of chronic
      cardiac failure with renal insufficiency.

PMID- 11327015
TI  - [Effects of tripchlorolide (T4) of Tripterygium Wilfordii Hook on the production
      of immunoglobulins by peripheral blood mononuclear cells and by synovial cells of
      rheumatoid arthritis patients in vitro].
AB  - Tripchlorolide(T4) is an active ingredient recently isolated from Tripterygium
      Wilfordii Hook. The in vitro effects of T4 on the peripheral blood mononuclear
      cells(PBMC) of healthy persons(n = 10), the digested single synovium cells(DSSC)
      (n = 3) and PBMC(n = 6) from RA patients on production of immunoglobulins (Ig)
      were studied using Elisa method. The results showed that T4 at concentrations
      from 5 ng.ml-1 to 35 ng.ml-1 significantly reduced the production of Ig by PWM
      stimulated PBMC of healthy persons in a dose dependent manner. At concentration
      of 25 ng.ml-1, T4 also reduced the Ig secretion of RA-PBMC and DSSC. It is hoped
      that T4 would be an encouraging new drug of herbal nature for the treatment of
      RA.

PMID- 11327018
TI  - [The blocking effects of six antiarrhythmic drugs on transient outward current in
      rat ventricular myocytes].
AB  - The effects of six antiarrhythmic drugs on transient outward current (Ito) in rat
      ventricular myocytes were examined by using the patch-clamp whole-cell recording
      technique. Quinidine, nifedipine, and imipramine resulted in a concentration
      dependent inhibition of Ito with IC50s of 5.4, 10.9 and 6.0 mumol.L-1,
      respectively. All three agents produced a concentration-dependent increase in the
      rate of inactivation of Ito. Disopyramide, procainamide and E-4031 produced
      little inhibition of Ito even when present at 100 mumol.L-1. The results from
      this study show that quinidine, nifedipine and imipramine are potent inhibitors
      of Ito and that inhibition is mediated through preferential interaction with the
      open channel.

PMID- 11327017
TI  - [Protective effect of schisanhenol (SAL) on oxygen free radical induced injury of
      spleen lymphocytes in mice].
AB  - In the present paper the effects of Sal, an active component isolated from
      Kadsura Longipenduculata Finet et Gagnep, on oxygen free radical induced injury
      of murine spleen lymphocytes in vitro and in vivo were investigated. The results
      showed that Sal at 1 x 10(-4) mol.L-1 significantly inhibited the decrease of GSH
      content induced by Fe(2+)-Vit C and the increase of MDA formation induced by
      Fe(2+)-Cys in murine spleen lymphocytes. The decrease of membrane fluidity of
      lymphocytes under lipid peroxidation induced by Fe(2+)-Vit C was prevented by
      Sal. The damage of the lymphocyte surfaces induced by Fe(2+)-Vit C was also
      markedly reduced by Sal. Administration of Sal 20 mg.kg-1.d-1 for 8 d
      significantly increased the GSH content of the spleen lymphocytes in mice under
      high oxygen-stress. Meanwhile, the compensative increase of SOD activity in the
      spleen lymphocytes was reversed. The results suggest that Sal may protect murine
      spleen lymphocytes from the injury induced by oxygen free radicals.

PMID- 11327020
TI  - [Studies on X-ray diffraction pattern of traditional Chinese medicinal
      materials].
AB  - Traditional Chinese medicine(TCM) as prescribed by Chinese traditional physicians
      is usually available as "decoction slices" which calls for a ready method for
      assessment of quantity or even genuineness. Three groups of TCM drugs (radix
      Rubiae, bulbus Fritillariae and rhizoma Dioscoreae) were selected by using powder
      X-ray diffraction analysis with complete absorption profile. Topological
      regularity and characteristic peaks of the absorption profile were obtained as
      fingerprint in X-ray diffraction diagrams of the pertinent medicinal materials.
      We have discovered the similarities of 3 radix Rubiae samples gathered from
      different localities and their differences with Rubia tinctorum, the similarities
      and differences between 7 species belonging to Fritillaria Genus, the
      similarities of 2 rhizoma Dioscoreae samples from different localities and their
      differences with 2 counterfeits. The result points to a promising prospect in
      achieving an objective assessment of genuineness at TCM drugs.

PMID- 11327019
TI  - [Synthesis of S-9-(2,3-dihydroxypropyl)adenine (DHPA) analogs and their
      inhibition of S-adenosyl-L-homocysteine (SAH) hydrolase].
AB  - In order to search for new antiviral agents with high potency and low toxicity,
      eleven new acyclonucleosides were synthesized. Nucleic-acid bases were condensed
      with 3-chloro-2-methylpropene to give 5-8a. b, which were oxidized by N
      methylmorpholine-N-oxide in the presence of OsO4 to give vicinal dihydroxy
      acyclonucleosides 1-4a.b. Four DHPA analogs have been tested for the inhibitory
      activities on s-adenosyl-L-homocysteine hydrolase (SAH). Only compound 1 showed
      some enzyme inhibitory effect with IC50 of 1.1 mmol.L-1.

PMID- 11327027
TI  - [Study on liver targeting and sustained release hydroxycamptothecin
      polybutylcyanoacrylate nanoparticles].
AB  - The liver targeting and sustained release hydroxycamptothecin
      polybutylcyanoacrylate nanoparticles (HCPT-PBCA-NP) which were wrapped up with
      ployvinylpyrrolidone(PVP) were prepared by adsorption-enwrapping method. The
      morphology, size and size distribution, drug loading, release characteristics in
      vitro, distribution and pharmacokinetic parameters in animals of the PVP-HCPT
      PBCA-NP were studied. The results showed that the average diameter was 81.2 nm,
      drug loading was 1.22%. The release characteristics in vitro was in accord with
      Higuchi equation: Q = 0.0615 + 0.0940 square root of t.64.5% of the HCPT were
      concentrated in liver 15 min after iv PVP-HCPT-PBCA-NP. The plasma drug
      concentration-time curve of the HCPT in 5 rabbits was fitted to a two-compartment
      open model. The Vc was 3.548 L; T1/2 was 146.99 h; CL was 0.178 L.h-1. The method
      of preparation presented in this paper seems to have important reference value
      for the preparation of PBCA-NP of the insoluble drugs both in water and in oil.

PMID- 11327021
TI  - [Two new flavanone glycosides from Glycyrrhizia inflata].
AB  - Two new flavanone glycosides having two chains of sugar moeity were isolated from
      the roots of Glycyrrhizia inflata Bat by repeated CC and HPLC. They were
      identified to be liquiritigenin-7-O-beta-D-apiofuranosyl-4'-O-beta-D
      glucopyranoside(I) and liquiritigenin-7-O-beta-D-(3-O-acetyl)-apiofuranosyl-4'-O
      beta-D- glucopyranoside (II) on the basis of chemical and spectroscopic methods.

PMID- 11327029
TI  - [A comparative study on the pharmacokinetics of josamycin in Chinese Han, Uighur
      and Kazak healthy volunteers].
AB  - Six Han, 6 Uighur and 6 Kazak healthy volunteers took orally a single dose of
      1000 mg josamycin tablets. The concentrations of the drug in serum were detected
      with bioassay method. The results showed that the pharmacokinetic courses were
      very similar among these three ethnic groups and fitted to a one-compartment open
      model. The results in these three groups showed no significant difference.

PMID- 11327032
TI  - [Sanitary-epidemiological characteristics of preschool institutions].
AB  - A specific microbial landscape forms in children of preschool institutions (PSI).
      To identify their sanitary and epidemiological hazards, the authors proposes to
      use the most common PSI pathogenic and opportunistic microbes that allow specific
      risk factors to be detected. The pinworm egg seeding index is used to estimate
      the pollution of the institutional environment.

PMID- 11327031
TI  - [Use of nuclear magnetic resonance spectroscopy in drug metabolism studies].

PMID- 11327036
TI  - [Organization of State Sanitary and Epidemiological Surveillance via local social
      hygienic monitoring system].
AB  - State sanitary and epidemiological surveillance (SSES) centers have gained much
      experience in organizing sociohygienic monitoring (SHM). However, the common
      mechanism that may intrinsically combine SHM and SSES is lacking so far. The
      proposed model of the activities of SSES in the SHM system at the local
      management level may largely solve the facing problem and organize SSES in the
      local monitored area under the Russian Federation's Law "On Human Sanitary and
      Epidemiological Well-Being" under No. 52-[symbol: see text]3, passed on March 30,
      1999.

PMID- 11327028
TI  - [Effects of ohmefentanyl at anesthetic dose on plasma levels of corticosterone,
      cortisol and antidiuretic hormone in rats].
AB  - Ohmefentanyl (OMF) is a new mu opioid receptor agonist with high affinity and
      selectivity, and possesses anesthetic activity. With radioimmunoassay, the plasma
      levels of cortisol (C), corticosterone (CS) and antidiuretic hormone (ADH) in
      rats were measured. The results indicated that no significant differences in the
      plasma C, CS and ADH levels were observed between the saline control group and
      the OMF-treated group. Trauma (bone-crush injury) increased significantly the
      plasma CS level. However, pretreatment with OMF 4.0 micrograms.kg-1 reduced
      markedly the CS plasma levels in trauma-treated rats. The results suggest that
      OMF anesthesia itself showed no obvious effect on the plasma concentration of C,
      CS and ADH, but blocked the hormoral stress responses such as the increment of
      plasma CS level caused by trauma stimulus.

PMID- 11327034
TI  - [Bases of safe substance levels for unified sanitary standards].
AB  - The study was undertaken to detect substances whose threshold and safe levels
      cannot be used without their correction in order to provide unified sanitary
      standardization. The criteria for choosing the substances were their high
      stability, capacity of bioaccumulation, the presence of mutagenic and/or
      carcinogenic properties and great discrepancy between the values of chronic
      toxicity of a substance and structure-activity relationships, which are typical
      of the structural series it belongs to. The use of these criteria may identify
      155 substances standardized in water and 126 in the ambient air, whose threshold
      and safe levels in their oral and inhaled administrations are to be clarified.

PMID- 11327033
TI  - [Multiple chemical sensitivity syndrome. Review].

PMID- 11327035
TI  - [Tasks of social-hygienic monitoring as an important mechanism of human sanitary
      and epidemiological wellbeing].

PMID- 11327038
TI  - [Analytical surveillance of discharges of pharmaceutic plants].

PMID- 11327041
TI  - Six cephalometric formulae.

PMID- 11327037
TI  - [Sanitary education of workers of bakeries and pastry enterprises].
AB  - The paper presents experience with sanitary education of workers from food
      industrial enterprises. The study revealed a number of disadvantages of the
      methodological aspect of sanitary education of these workers. A sanitary
      education programme has been worked out for workers engaged in food and food
      processing industries (production of bread, baked goods, and confectionery) and
      approved by the State Sanitary and Epidemiological Surveillance Department),
      Ministry of Health of Russia on March 1999.

PMID- 11327043
TI  - Structural genomics takes off.

PMID- 11327039
TI  - [Determination of volatile phenols in the workplace air by piezo quartz micro
      weighing].

PMID- 11327040
TI  - [The term "absence" in standard documents on the quality of drinking water].

PMID- 11327042
TI  - Photo quiz. Envenomation from a spider bite.

PMID- 11327044
TI  - Macromolecular interactions: tracing the roots.

PMID- 11327045
TI  - ST-segment elevation in leads V1-V3 in patients with LBBB.

PMID- 11327049
TI  - Interview with Dr. Jean Pierre Armand.

PMID- 11327046
TI  - Heart rate variability and QT dispersion in mitral valve prolapse.

PMID- 11327047
TI  - Development and aging of forest trees.

PMID- 11327050
TI  - Comments on: Involvement of adenomatous polyposis coli (APC) beta-catenin
      signalling in human breast cancer, Johnsson M, Borg A, Nilbert M, Andersson, T.
      Eur.J. Cancer 2000, 36, 242-248.

PMID- 11327051
TI  - Differentiation of positional isomers of nitro meso-tetraphenylporphyrins by
      tandem mass spectrometry.
AB  - We studied by tandem mass spectrometry two isomers of nitro meso
      tetraphenylporphyrin, one with a nitro group in the para position of a phenyl
      ring and the other with the same group in a beta-pyrrolic position, and their
      copper complexes. Collisional activation of the molecular ions of both free-base
      porphyrins and of their copper complexes produces an array of product ions that
      permit ready differentiation of the two positional isomers. The diagnostic ions,
      when the nitro group is in a beta-pyrrolic position, may be produced through
      intramolecular and double cyclization processes, triggered by the interaction of
      the nitro substituent with the neighboring meso-phenyl ring. These diagnostic
      ions do not form when the nitro group is in the para position. The gas-phase
      processes have precedents in solution chemistry.

PMID- 11327048
TI  - Photosynthesis and primary metabolism.

PMID- 11327053
TI  - [Recommendations for basic and advanced cardiopulmonary resuscitation in adults.
      SEDAR (Spanish Society for Anesthesiology and Resuscitation) ].

PMID- 11327052
TI  - Platelet activating factor degradation in tear fluid from guinea pigs with
      allergic conjunctivitis.
AB  - The purpose of this study was to investigate the role of platelet-activating
      factor (PAF) and PAF acetylhydrolase (AH) in conjunctiva. The influence of PAF on
      conjunctival vascular permeability and the presence of PAF or its metabolites in
      tears from guinea pigs with allergic conjunctivitis were investigated. We
      instilled PAF to the eyes of guinea pigs and evaluated vascular permeability.
      Tear samples were collected from passively sensitized guinea pigs, and the
      concentration of PAF and its metabolites determined by liquid chromatography
      tandem mass spectrometry. Exogenous PAF degradation in tear samples was evaluated
      with or without diisopropyl fluorophosphate (DFP). Topically applied PAF
      increased vascular permeability in conjunctiva. In the tear samples from guinea
      pigs with allergic conjunctivitis, PAF could not be detected. However, 40 +/- 6
      ng/ml of lyso-platelet activating factor (lyso-PAF) and 230 +/- 50 ng/ml of 1
      alkyl-2-acyl-sn-glycero-3-phosphocholine were detected at 10 min after challenge.
      Exogenous PAF was rapidly degraded in the tear samples from guinea pigs with
      allergic conjunctivitis, but not from normal guinea pigs. This PAF degradation
      was inhibited by DFP. These results suggest that PAF in the tear fluid is quickly
      hydrolyzed to lyso-PAF by PAF AH, which may be released or activated in allergic
      conjunctivitis.

PMID- 11327054
TI  - A 2-step non-surgical procedure and systemic antibiotics in the treatment of
      rapidly progressive periodontitis.
AB  - BACKGROUND: In the last few years knowledge about periodontal infections has
      increased enormously, nevertheless practitioners are still seeking guidelines for
      suitable treatment concepts. METHODS: The aim of this study was to examine the
      effect of doxycycline, metronidazole, and clindamycin used adjunctively in a 2
      step nonsurgical procedure in patients with rapidly progressive periodontitis
      (RPP). The first step included scaling, root planing, and polishing (SRP) in each
      quadrant using 4 to 5 visits. The second step included full-mouth enhanced root
      planing (RP) and wound dressing in 1 or 2 visits after SRP and the beginning of
      antibiotic therapy. Forty-eight patients (mean age 32.4 years) with generalized
      RPP, with an average of 16 sites with probing depths (PD) deeper than 8 mm, and
      high counts of Porphyromonas gingivalis were randomly assigned to 4 different
      groups: group 1 (doxycycline) n = 12, group 2 (metronidazole) n = 15, group 3
      (clindamycin) n = 11, and group 4 (control group; no antibiotic treatment) n =
      10. Clinical evaluations, including plaque index (PI), sulcus bleeding index
      (SBI), probing depth (PD), clinical attachment level (CAL), and bacteriological
      and crevicular cell sampling, were done at baseline (BL), 3 weeks after SRP, and
      6 and 24 months after RP. RESULTS: After the first step (SRP), we observed an
      improvement of PI and SBI in all 4 groups, but did not see any statistically
      significant PD reduction 3 weeks after SRP compared to baseline. However, 6 and
      24 months after the second step (RP) we observed a significantly greater
      reduction of PD in groups 2 and 3 and a significantly greater CAL gain in
      comparison to groups 1 and 4. After 24 months, the attachment level gain in group
      1 and group 4 was less than 1.5 mm, and less than 1.0 mm in PD site categories 6
      to 9 mm and >9 mm. PI showed no significant difference between the groups
      throughout the period after SRP until 24 months, compared to 3 weeks after SRP.
      SBI decreased most in the metronidazole and clindamycin groups. P. gingivalis and
      Actinobacillus actinomycetemcomitans were almost completely eradicated in these 2
      groups 24 months after RP. In addition, the phagocytotic capacity of crevicular
      polymorphonuclear neutrophils was increased in groups 2 and 3 after the second
      step. CONCLUSIONS: The present results show that metronidazole and clindamycin
      are effective antibiotics when used adjunctively in a 2-step nonsurgical
      procedure of scaling and root planing in RPP patients.

PMID- 11327059
TI  - Characterization of proliferation and cellular wound fill in periodontal cells
      using an in vitro wound model.
AB  - BACKGROUND: The therapeutic success of periodontal regenerative therapy may be
      compromised by our limited understanding of the wound healing process. Wound
      healing requires the coordination of complex cellular and molecular interactions.
      Recently, using an in vitro wound model, our laboratory has shown that gingival
      fibroblasts (GF) fill an in vitro wound more rapidly than periodontal ligament
      cells (PDL). This suggests that there may be differences in the levels of
      proliferation for these 2 cell types during the wound healing process. Such
      specific cell type differences may be significant in clinical outcomes of
      regenerative therapy. Therefore, the aim of this research was to characterize and
      compare the levels of both proliferation and cellular wound fill between GF and
      PDL using our in vitro wound model. METHODS: Primary cultures of human PDL and GF
      cells were established from explanted tissue, and passaged to 12-well tissue
      culture plates. Triplicate cultures of both cell types were grown to confluence
      and in vitro wounds were mechanically created, removing a 3 mm wide band of the
      cell layer across the diameter of the wells. The wells were then incubated for 2,
      6, or 9 days in media containing either 0.1% or 10% fetal bovine serum (FBS). At
      each time point, cells were pulsed with 5-bromo, 2-deoxyuridine (BrdU), fixed,
      and nuclei stained to measure DNA synthesis (as a measure for proliferation).
      Cells were counter stained with cytoplasmic stain to measure cell number.
      Quantitative analysis distant from (area of interest [AOI 1]), next to (AOI 2),
      and within the wound boundaries (AOI 3 and 4) was accomplished using computer
      assisted histomorphometry. RESULTS: The levels of proliferation and cellular fill
      for each cell type were assessed relative to time and AOI. Overall, the PDL
      displayed greater (P <0.01) levels of proliferation than the GF. For both cell
      types, proliferation was found to be significantly (P<0.001) greater at day 2
      compared to other time points. PDL displayed greater levels of proliferation than
      GF in all AOI, with this difference reaching significance (P<0.02) within the
      cell layer (AOI 1 and 2). When comparing levels of cellular fill in 10% FBS, GF
      displayed greater wound fill than the PDL. This difference was significant at day
      6 (P <0.05) for both the marginal (AOI 3) and central (AOI 4) portions of the
      wound. CONCLUSIONS: These findings, demonstrating unique differences between PDL
      and GF with respect to proliferation and wound fill in an in vitro model, suggest
      that there may be cell-specific differences in cellular activity critical to
      periodontal wound healing. In addition, the results of this study show that the
      cellular proliferation response may not accurately reflect the overall wound
      healing response.

PMID- 11327056
TI  - Comparison of calcium sulfate and autogenous bone graft to bioabsorbable
      membranes plus autogenous bone graft in the treatment of intrabony periodontal
      defects: a split-mouth study.
AB  - BACKGROUND: Current literature shows that calcium sulfate can be used in guided
      tissue regeneration. Its biocompatibility and resorbability give it significant
      advantages in the treatment of periodontal and endodontic defects. Clinically
      guided tissue regeneration procedures have demonstrated significant positive
      clinical change, beyond that achieved with debridement alone, in treating
      intraosseous defects. The aim of the present investigation was to evaluate the
      clinical results obtained with autologous bone plus calcium sulfate, and to
      compare them with the results obtained using autologous bone plus membrane.
      METHODS: A total of 12 patients were treated in the present investigation. A
      split-mouth design was utilized. Twelve 3-wall periodontal defects were treated
      with calcium sulfate plus autologous bone graft (test) and compared with 12
      contra-lateral defects treated with a bioabsorbable membrane plus autologous bone
      graft (control). Before the surgical procedure, patients were instructed about
      oral hygiene and scaling and root planing (SRP) was completed. Probing depth
      (PD), clinical attachment level (CAL), and bleeding on probing (BOP) were
      recorded at baseline and 6 months. RESULTS: There were no statistical differences
      between test and control defects at baseline. BOP was 58% and 50% for control and
      test defects, respectively. Mean PD was 7.75+/-0.96 mm (control) and 8.0+/-1.28
      mm (test). Mean CAL was 8.58+/-1.31 mm (control) and 8.83+/-0.91 mm (test). At 6
      months, mean PD was 3.41+/-0.51 (P = 0.0022) for control defects and 3.58+/-0.51
      (P = 0.0022) for test defects. CAL showed a mean gain of 5+/-0.85 for controls (P
      = 0.0022) and 5.25+/-0.75 for test defects (P = 0.0022). Thus, there was a mean
      reduction of PD of 4.33 mm (56%) for control sites and 4.42 mm (55%) for test
      sites. The mean clinical attachment gain was 3.57 mm for control sites and 3.58
      mm for test sites. As there were no sham-operated controls, it is not clear that
      the healing of these test or control-treated sites was any better than similar 3
      walled defects sham operated. CONCLUSIONS: Both therapies led to short-term
      improvement of the measured parameters; neither was superior to the other.

PMID- 11327055
TI  - Effect of repeated local minocycline administration on periodontal healing
      following guided tissue regeneration.
AB  - BACKGROUND: Infection after a periodontal surgical site has been prepared for
      guided tissue regeneration (GTR) is one of the common complications that can
      compromise healing. The purpose of this study was to assess the effect of
      repeated local antimicrobial therapy following GTR for improving clinical
      attachment gains, and to histologically evaluate the various cell populations and
      bacterial contamination of the retrieved expanded polytetrafluoroethylene
      membrane (ePTFE). METHODS: Forty periodontal intrabony defects in 40 patients
      were treated by a flap procedure that included the use of ePTFE membranes to
      allow GTR. Patients were randomly assigned to 2 treatment groups: 20 patients
      were treated with the ePTFE alone (control group), and the other 20 were treated
      with the ePTFE combined with the administration of a weekly repeated local
      application of minocycline ointment for 8 weeks after membrane placement (test
      group). The membranes were retrieved 6 weeks after the initial surgery and
      sectioned serially in a coronal-apical plane. The sections were then divided into
      9 fields and examined by light microscopy for the presence of inflammatory cells
      and oral bacteria. Clinical measurements were taken at the time of baseline
      examination and at a 6-month follow-up examination after removal of the ePTFE.
      RESULTS: At the 6-month follow-up examination, control and test groups showed
      significant improvement; i.e., reduction in the probing depth and increased
      clinical attachment gain compared with the values at the baseline examination.
      However, the mean clinical attachment gain of the test group (3.0+/-0.3 mm) was
      significantly (P = 0.03) greater than that of the control group (2.0+/-0.5 mm).
      Histologically, the total number of the cells of both groups was similar. In both
      groups, mononuclear cells were dominant and fibroblasts, neutrophils, and plasma
      cells were rarely encountered. There was a tendency for the number of macrophages
      to be somewhat higher in the control group. The total number of bacteria in the
      test group was significantly less than that in the control group. The number of
      bacteria in both control and test groups decreased toward the apical portion.
      CONCLUSIONS: In the present study, clinical attachment gain of intrabony defects
      following GTR was favorable with repeated local administration of minocycline
      ointment. However, a complete microbial eradication was not achieved.

PMID- 11327057
TI  - Thrombin-stimulated growth, clustering, and collagen lattice contraction of human
      gingival fibroblasts is associated with its protease activity.
AB  - BACKGROUND: Thrombin is a serine protease produced following gingival tissue
      injury or inflammation. It regulates the functional behavior of injury
      neighboring cells via the activation of specific protease-activated receptors
      (PAR). Thrombin's role in gingival tissue healing and inflammatory response
      processes is not yet well understood. METHODS: We investigated the effects of
      thrombin on gingival fibroblast (GF) growth [3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyl-tetrazolium bromide (MTT) assay], collagen lattice contraction, and
      associated morphological changes. RESULTS: Thrombin (>1 U/ml), but not thrombin
      receptor (PAR-1) agonist peptide (SFLLRN, single letter amino acid code,
      abbreviated as TRAP, 1 to 50 microg/ml), stimulated the growth and clustering of
      cultured human GF in vitro. Growth-stimulatory effects of thrombin were inhibited
      by D-Phe-Pro-ArgCH2Cl (PPACK), a serine protease inhibitor. By contrast, trypsin
      (>10 microg/ml), a PAR-2 activator, suppressed the growth of GF. Thrombin (>0.2
      U/ml) and TRAP (10 to 25 microg/ml), but not trypsin, prostaglandin E2 (0.01 to
      0.5 microg/ml), or bovine serum albumin (BSA) (1 to 80 microg/ml), induced the GF
      populated collagen lattice contraction within 30 to 60 minutes of exposure. The
      thrombin-induced collagen lattice contraction was inhibited by PPACK (20
      microg/ml) and an actin filament polymerization inhibitor, cytochalasin B (1
      microg/ml). The collagen lattice contraction induced by TRAP was also inhibited
      by cytochalasin B, but not by PPACK. Using a reverse-transcriptase polymerase
      chain reaction (RT-PCR), the expression of PAR-1, and to a lesser extent PAR-3,
      was observed for human GF, although little PAR-2 and PAR-4 expression was noted.
      CONCLUSIONS: These results indicate that thrombin is important in periodontal
      wound healing and inflammatory processes by promoting the growth and contraction
      of GF. The stimulatory effects of thrombin are associated with its protease
      activation of thrombin receptors.

PMID- 11327060
TI  - The effects of platelet-derived growth factor-BB on periodontal cells in an in
      vitro wound model.
AB  - BACKGROUND: Platelet-derived growth factor (PDGF-BB) has been shown to enhance
      periodontal regeneration. Principles of guided tissue regeneration dictate that
      one of the goals of therapy is to modulate the wound healing processes to favor
      repopulation of the wound with cells derived from the periodontal ligament rather
      than from the gingival tissues. Using an in vitro wound model, gingival
      fibroblasts (GF) have been shown to fill a wound space significantly faster than
      periodontal ligament cells (PDL). There are no data reported directly comparing
      the response of these 2 cell types to PDGF-BB within such a wound model.
      Therefore, the aims of this research were: 1) to characterize both the
      proliferative and wound fill (WF) effects of PDGF-BB within an in vitro model and
      2) to compare specific growth factor effects between GF and PDL. METHODS: Primary
      cultures of both human PDL and GF were derived from explanted tissues and
      passaged to 12-well tissue culture plates. Triplicate cultures of both cell types
      were grown to confluence and in vitro wounds were mechanically created, removing
      a 3 mm wide band of the cell layer across the diameter of the wells. The wells
      were then incubated for 2, 6, and 9 days in media containing 0.1% fetal bovine
      serum (FBS) and 1 of 5 concentrations of PDGF-BB. At each time point, cells were
      pulsed with 5-bromo, 2-deoxyuridine (BrdU) fixed, and nuclei were stained to
      measure BrdU incorporation (as a measure for proliferation). Cells were counter
      stained with cytoplasmic stain to measure cell number. Quantitative analyses
      within the wound boundaries, marginally (area of interest [AOI] 1) and centrally
      (AOI 2), were accomplished using computer-assisted histomorphometry. RESULTS: PDL
      exhibited a significantly greater proliferative response to PDGF-BB in both AOI
      when compared to GF (P <0.0001). The PDL exhibited increased levels of
      proliferation at concentrations of PDGF-BB greater than or equal to 10 ng/ml. By
      contrast, GF displayed no increase in proliferation in response to stimulation
      with PDGF-BB at any of the concentrations tested when compared to negative
      controls. The wound fill (WF) responses to PDGF-BB were similar between PDL and
      GF, with both cell types responding in an all or none fashion when measured at
      day 2, and in a concentration-dependent manner at later time points. The only
      significant difference in WF between PDL and GF occurred in AOI 2 in negative
      control medium (0 ng/ml of PDGF-BB), with GFs having greater (P <0.01) levels of
      WF over the 9 days. CONCLUSION: The findings from this study demonstrate
      differing effects of PDGF-BB on the proliferation of PDL and GF in this in vitro
      model. These results suggest that there may be cell-specific differences critical
      to periodontal wound healing that may be exploited in the development of new
      therapies.

PMID- 11327058
TI  - Participation of periodontal ligament cells with regeneration of alveolar bone.
AB  - BACKGROUND: It is important to clarify the participation of periodontal ligament
      (PDL) cells in the regeneration of alveolar bone to establish a reliable approach
      for obtaining periodontal regeneration. The aim of this study was to determine
      whether PDL cells play an important role in alveolar bone repair during the
      course of periodontal regeneration. METHODS: In an in vitro study, the expression
      of the osteoblast phenotype, such as alkaline phosphatase activity and
      parathyroid hormone-dependent 3',5'-cyclic adenosine monophosphate accumulation,
      was investigated in dog PDL cells (DPLC) and dog bone cells isolated from
      mandibles (DBC). In a related study, the roots of mandibular third premolars
      extracted from aged dogs were divided into a PDL(+) group, in which the PDL was
      preserved, and a PDL(-) group, in which the PDL was removed. These roots were
      respectively transplanted into surgically created bone cavities with buccal and
      interproximal bone defects in an edentulous area, prepared in advance by
      extraction of mandibular fourth premolars. These bone defects with the
      transplanted roots were completely covered with submerged physical barrier
      membranes. New bone formation and new connective tissue attachment, which require
      new cementum and insertion of functionally oriented new collagen fibers of
      periodontal ligament, were histomorphometrically assessed, and were compared
      between the PDL(+) and PDL(-) groups 6 weeks after transplantation. RESULTS: Both
      cultured DPLC and DBC exhibited the osteoblast phenotype. New connective tissue
      attachment was observed only in the PDL(+) group. However, alveolar bone was
      almost completely regenerated to the original bone height in both the PDL(+) and
      PDL(-) groups, and the amount of newly formed bone was not significantly
      different between the 2 groups. CONCLUSIONS: DPLC retain the capability to
      differentiate into an osteoblast lineage and may act in the regeneration of
      periodontal ligament with new cementum formation, whereas these cells may have a
      limited influence on alveolar bone formation during the course of periodontal
      regeneration.

PMID- 11327062
TI  - Is loss of attachment due to root planning and scaling in sites with minimal
      probing depths a statistical or real occurrence?
AB  - BACKGROUND: Following root planing and scaling many studies have implied an
      association between a loss of clinical attachment at sites with initially shallow
      pockets (1 to 3 mm) and gains in attachment level for deeper probing depths.
      However, these effects are also consistent with a statistical phenomenon referred
      to as regression towards the mean. This principle suggests that extreme values
      will moderate the next time they are recorded. The purpose of this report was to
      estimate the effect that regression towards the mean has on perceived changes in
      attachment level after root planing and scaling. METHODS: During the initial
      examination, 2 different investigators conducted 2 full-mouth probings. Two
      quadrants were randomly selected to be root planed and scaled until the root
      surfaces were smooth by tactile touch of an explorer. The 2 remaining quadrants
      were not treated. At 4 to 6 weeks after treatment, another full mouth probing was
      done. An examiner who was blind to the quadrants that had been scaled measured
      attachment level and probing depth after therapy. This study design provided
      periodontal measurements before and after root planing and scaling, measurements
      before and after a period of 4 to 6 weeks of no therapy, and duplicate
      measurements at the beginning of the study. RESULTS: Using the repeat examination
      when no true change could occur, shallow sites (< or =3 mm of probing depth)
      showed average negative differences between repeat attachment level measurements
      (-0.23 mm), which mimicked loss of periodontal attachment. Deep sites, (>6 mm)
      showed average positive values (0.40) mimicking gain in attachment level. These
      results suggest that regression towards the mean is a significant effect in this
      data set. Both shallow non-scaled and scaled sites had similar differences in
      repeat measures (-0.28 mm, -0.25 mm) which were also similar to and not
      statistically different from changes after therapy for both non-scaled (-0.21 mm)
      and scaled sites (-0.08 mm). Thus not only does this data set exhibit regression
      towards the mean, but it explains the majority of perceived loss of periodontal
      attachment after scaling at sites that have minimal probing depth. CONCLUSIONS:
      These results suggest that the majority of perceived loss of attachment due to
      scaling at sites of minimal probing depth that have been reported in many studies
      may be due a statistical phenomenon called regression towards the mean.

PMID- 11327061
TI  - Enamel matrix derivative induces matrix synthesis by cultured human periodontal
      fibroblast cells.
AB  - BACKGROUND: Periodontal wound healing and regeneration require that new matrix be
      synthesized, creating an environment into which cells can migrate. One agent
      which has been described as promoting periodontal regeneration is an enamel
      matrix protein derivative (EMD). Since no specific growth factors have been
      identified in EMD preparations, it is postulated that EMD acts as a matrix
      enhancement factor. This study was designed to investigate the effect of EMD in
      vitro on matrix synthesis by cultured periodontal fibroblasts. METHODS: The
      matrix response of the cells was evaluated by determination of the total
      proteoglycan synthesis, glycosaminoglycan profile, and hyaluronan synthesis by
      the uptake of radiolabeled precursors. The response of the individual
      proteoglycans, versican, decorin, and biglycan were examined at the mRNA level by
      Northern blot analysis. Hyaluronan synthesis was probed by identifying the
      isotypes of hyaluronan synthase (HAS) expressed in periodontal fibroblasts as HAS
      2 and HAS-3 and the effect of EMD on the levels of mRNA for each enzyme was
      monitored by reverse transcription polymerase chain reaction (RTPCR). Comparisons
      were made between gingival fibroblast (GF) cells and periodontal ligament (PDLF)
      cells. RESULTS: EMD was found to significantly affect the synthesis of the mRNAs
      for the matrix proteoglycans versican, biglycan, and decorin, producing a
      response similar to, but potentially greater than, mitogenic cytokines. EMD also
      stimulated hyaluronan synthesis in both GF and PDLF cells. Although mRNA for HAS
      2 was elevated in GF after exposure to EMD, the PDLF did not show a similar
      response. Therefore, the point at which the stimulation of hyaluronan becomes
      effective may not be at the level of stimulation of the mRNA for hyaluronan
      synthase, but, rather, at a later point in the pathway of regulation of
      hyaluronan synthesis. In all cases, GF cells appeared to be more responsive to
      EMD than PDLF cells in vitro. CONCLUSIONS: EMD has the potential to significantly
      modulate matrix synthesis in a manner consistent with early regenerative events.

PMID- 11327064
TI  - Periodontal treatment with an Er: YAG laser compared to scaling and root planing.
      A controlled clinical study.
AB  - BACKGROUND: The aim of the present study was to compare the effectiveness of an
      Er:YAG laser to that of scaling and root planing for non-surgical periodontal
      treatment. METHODS: Twenty patients with moderate to advanced periodontal
      destruction were treated under local anesthesia and the quadrants were randomly
      allocated in a split-mouth design to either Er:YAG laser using an energy level of
      160 mJ/pulse and 10 Hz or scaling and root planing (SRP) using hand instruments.
      Clinical assessments of plaque index (PI), gingival index (GI), bleeding on
      probing (BOP), probing depth (PD), gingival recession (GR), and clinical
      attachment level (CAL) were made prior to and at 3 and 6 months after treatment.
      Subgingival plaque samples were taken at each appointment and analyzed using
      darkfield microscopy for the presence of cocci, non-motile rods, motile rods, and
      spirochetes. Differences in clinical parameters and prevalence of bacterial
      species were analyzed using the paired t-test. RESULTS: The PI remained nearly
      unchanged while a significant reduction of the GI occurred in both groups after 6
      months (P < or =0.001, P< or =0.001, respectively). The mean value of BOP
      decreased in the laser group from 56% at baseline to 13% after 6 months (P < or
      =0.001) and in the SRP group from 52% at baseline to 23% after 6 months (P < or
      =0.001). The mean value of the PD decreased in the laser group from 4.9+/-0.7 mm
      at baseline to 2.9+/-0.6 mm after 6 months (P< or =0.001) and in the SRP group
      from 5.0+/-0.6 mm at baseline to 3.4+/-0.7 mm after 6 months (P < or =0.001). The
      mean value of the CAL decreased in the laser group from 6.3+/-1.1 mm at baseline
      to 4.4+/-1.0 mm after 6 months (P < or =0.001) and in the SRP group from 6.5+/
      1.0 mm at baseline to 5.5+/-1.0 after 6 months (P < or =0.001). The reduction of
      the BOP score and the CAL improvement was significantly higher in the laser group
      than in the SRP group (P < or =0.05, P < or =0.001, respectively). Both groups
      showed a significant increase of cocci and non-motile rods and a decrease in the
      amount of motile rods and spirochetes. CONCLUSIONS: An Er:YAG laser may represent
      a suitable alternative for non-surgical periodontal treatment.

PMID- 11327063
TI  - Matrix metalloproteinases (MMP-8 and -9) and neutrophil elastase in gingival
      crevicular fluid of cyclosporin-treated patients.
AB  - BACKGROUND: Gingival overgrowth (GO) is one of the most important side effects of
      cyclosporin A (CsA) medication, but its pathogenesis is not completely
      understood. The aim of this study was to identify and compare collagenase-2 (MMP
      8), gelatinase-B (MMP-9), and neutrophil (PMN)-elastase levels in gingival
      crevicular fluid (GCF) from 15 renal transplant patients receiving CsA therapy
      and exhibiting CsA GO, 14 patients with gingivitis, and 10 periodontally healthy
      subjects. METHODS: Clinical data were obtained on plaque index, papilla bleeding
      index, and hyperplastic index from each site studied. GCF samples and clinical
      data were collected from: 2 sites exhibiting CsA GO (CsA GO+) and 2 sites not
      exhibiting CsA GO (CsA GO-) in each CsA-treated patient; 2 diseased sites in each
      patient with gingivitis; and 2 healthy sites in each subject with clinically
      healthy periodontium. CsA GO+ and CsA GO- sites were divided into 2 subgroups as
      clinically not inflamed (PBI = 0) and inflamed (PBI > or =1). GCF MMP-8, MMP-9,
      and PMN-elastase levels were analyzed by immunofluorometric assay. RESULTS: GCF
      MMP-8 and -9 levels and clinical degrees of gingival inflammation in CsA GO+
      sites were similar to those in diseased sites. However, GCF elastase levels were
      significantly lower in CsA GO+ sites compared to those in diseased sites. GCF MMP
      8, -9 and PMN-elastase levels were not different between CsA GO- sites and
      healthy sites. Additionally, GCF MMP-8 and -9 levels in inflamed CsA GO+ sites
      were higher but not statistically significantly than those in diseased sites. In
      contrast, GCF PMN-elastase levels in inflamed CsA GO+ sites were significantly
      lower than the levels in diseased sites. CONCLUSIONS: These results show that CsA
      therapy does not have a significant effect on GCF MMP-8 and MMP-9 levels, but the
      gingival inflammation seems to be the main reason for their elevations. However,
      low GCF PMN-elastase levels can be an important factor in the pathogenesis of CsA
      induced gingival overgrowth. CsA therapy does not eliminate the potential use of
      GCF MMP-8 and -9 as future diagnostic markers of gingival inflammation.

PMID- 11327065
TI  - Relationship of periodontopathic bacteria with early-onset periodontitis in
      Down's syndrome.
AB  - BACKGROUND: Down's syndrome (DS) patients often develop severe early-onset
      marginal periodontitis in early adulthood; however, there is little information
      available on the microbiology of DS periodontitis. METHODS: Subgingival plaque
      specimens were taken from 67 DS young adults and 41 age-matched systemically
      healthy individuals with mental disabilities (MD). The prevalence of 10 possible
      periodontopathic bacterial species, Actinobacillus actinomycetemcomitans,
      Porphyromonas gingivalis, Bacteroides forsythus, Treponema denticola, Prevotella
      intermedia, Prevotella nigrescens, Capnocytophaga ochracea, Capnocytophaga
      sputigena, Campylobacter rectus, and Eikenella corrodens, were investigated in
      their subgingival plaque samples using a polymerase chain reaction method. The
      detection of P. gingivalis fimA genotypes was also performed in P. gingivalis
      positive samples. RESULTS: Although DS subjects generally develop an earlier and
      more extensive periodontal breakdown than those with MD, no significant
      differences were observed in the bacterial profiles. The profiles of subjects
      with periodontitis were significant in DS, but not in MD. The prevalence of P.
      gingivalis, B. forsythus, and P. intermedia were significant in the DS
      periodontitis group, compared to DS gingivitis group. Moreover, the occurrence of
      P. gingivalis with the type II fimA gene was significantly related to
      periodontitis in both DS and MD, with odds ratios of 6.32 and 12.03,
      respectively. CONCLUSIONS: These results suggest that early-onset periodontitis
      in DS is mainly due to the more susceptible host for the causative microbial
      agents including P. gingivalis with type II fimA.

PMID- 11327066
TI  - One-stage full-mouth disinfection. Long-term microbiological results analyzed by
      checkerboard DNA-DNA hybridization.
AB  - BACKGROUND: Recent studies reported significant, additional clinical and
      microbiological improvements when severe adult periodontitis was treated via the
      one-stage full-mouth (OSFM) disinfection approach, instead of a standard
      treatment scheme with staged instrumentation per quadrant. The OSFM disinfection
      involves dealing with the remaining oropharyngeal niches such as tonsils, saliva,
      tongue, and mucosa. The OSFM disinfection procedure involves scaling and root
      planing of all pockets within 24 hours in combination with chlorhexidine
      application to all oropharyngeal niches (chairside and at home for 2 months).
      This study aimed to compare the microbiological shifts with the OSFM approach
      versus standard therapy. METHODS: Nineteen patients with advanced chronic
      periodontitis (AP) and 12 patients with early-onset periodontitis (EOP) were
      randomly assigned to the test and control groups. The control group (9 AP
      patients, 6 EOP patients) was scaled and root planed, per quadrant, with 2-week
      intervals. The test group (10 AP patients and 6 EOP patients) underwent OSFM
      disinfection treatment. At baseline and after 2, 4, and 8 months, pooled
      subgingival plaque samples were taken from single- and multi-rooted teeth. The
      presence and levels of 30 subgingival taxa were determined using whole genomic
      DNA probes and checkerboard DNA-DNA hybridization. RESULTS: Both treatments
      resulted in important reductions of the pathogenic species up to 8 months after
      therapy, both for their detection level and frequency. The OSFM disinfection
      resulted in an additional improvement, especially in the AP group. P. gingivalis
      and B. forsythus were reduced below detection level. The number of beneficial
      species remained nearly unchanged. CONCLUSIONS: The OSFM disinfection results in
      supplementary reductions of periodontal pathogens even after 8 months in the
      treatment of patients with advanced or early-onset periodontitis.

PMID- 11327067
TI  - Identification and consequences of distinct Loe-Silness gingival index examiner
      styles for the clinical assessment of gingivitis.
AB  - BACKGROUND: In clinical studies, gingivitis is most frequently assessed by the
      Loe-Silness gingival index (GI). The objective of this work was to develop an
      understanding of how clinicians experienced with GI differ with respect to how
      they apply GI and to assess the impact of different examination styles on
      statistical outcomes and magnitude of treatment differences. METHODS: A method
      was developed to mathematically relate the average GI score and degree of
      bleeding observed for a subject. Graphical analyses were used to profile examiner
      styles with respect to using the GI index. A prospective single-center, examiner
      blind study comparing the effects of a staggered prophylaxis on gingivitis was
      then conducted, where a difference in gingivitis was created between two balanced
      groups by providing subjects a prophylaxis at two staggered time points. Subjects
      were assigned to one of two cohorts; within each cohort, group 1 subjects
      received a dental prophylaxis following the baseline examination and group 2
      subjects received a dental prophylaxis 8 weeks later. Five to 7 days after the
      group 2 prophylaxis, all subjects were examined for GI. Twelve experienced
      clinicians participated. RESULTS: Retrospective analyses indicated the presence
      of distinct examiner styles which are based on the frequency that a given GI
      score (0, 1, 2, or 3) is measured by a clinician. In the prospective study, all
      12 examiners observed statistically significant differences between the
      prophylaxis treatment groups at the final visit for both mean number of bleeding
      sites and mean GI; the magnitude ranged from 21.5% to 84.6% for mean number of
      bleeding sites and 9.4% to 39.2% for mean GI. There were 4 distinct styles
      employed by these experienced clinicians. CONCLUSIONS: Varying examiner styles
      impact the structure of resulting data. Importantly, the implementation of
      arbitrary thresholds (e.g., 20%) regarding percent treatment differences between
      groups as a guideline for judging the clinical significance is scientifically
      unsupported. A more scientific criterion in the field of gingivitis clinical
      testing would be the independent demonstration of statistical superiority
      compared to a negative control and/or a demonstration of similar or superior
      efficacy to clinically proven positive controls. In addition, interexaminer
      calibration is a mechanism that can be utilized to minimize the impact of
      different examiner styles in clinical settings involving more than one examiner.

PMID- 11327068
TI  - Dental unit waterline contamination and its possible implications during
      periodontal surgery.
AB  - BACKGROUND: Dental unit waterline contamination has become a concern to clinical
      dentistry. This concern arises from the fact that bacteria sloughed from
      established biofilms in dental unit waterlines increase heterotrophic bacteria
      counts in water exiting these units. METHODS: Scanning microscopy and bacterial
      viability staining were used to examine the sessile and planktonic biofilm
      present in dental unit waterlines and water samples, respectively. In addition,
      the limulus amebocyte assay was used to measure the lipopolysaccharide (LPS)
      levels in water samples. RESULTS: All dental unit waterlines were coated with a
      well-established biofilm made up of filamentous and bacillus-like microorganisms.
      Water samples collected from these dental units contained high numbers of
      individual bacteria and bacterial aggregates. A viability staining technique
      identified significantly more bacteria in water than could be cultured, and 64%
      of the total bacterial population stained as nonvital. Since the bacterial load
      (viable and nonviable) was high, we examined the LPS in dental unit water
      samples. The mean LPS levels in water collected from high-speed and air/water
      lines in use were 480 and 1,008 endotoxin units (EU)/ml. This was significantly
      higher than the mean level of 66 EU/ml found in water samples collected from
      adjacent clinic sinks. The LPS level at the start of the day (2,560 EU/ml) was
      reduced by 70% with 1 minute of flushing (800 EU/ml). Flushing times of 5 and 10
      minutes were not able to reduce LPS levels to zero. CONCLUSION: The presence of
      high heterotrophic bacterial counts, sloughing biofilm, and high LPS levels are
      discussed in relation to patient risk and periodontal wound healing biology.

PMID- 11327069
TI  - Evaluation of ultrasonic scaling unit waterline contamination after use of
      chlorine dioxide mouthrinse lavage.
AB  - BACKGROUND: An infection control problem in dental operatories which is not fully
      controlled is waterline contamination by heterotrophic mesophilic bacteria. These
      bacteria are present in water supplies as a planktonic phase and adhere to the
      lumen of tubings as a biofilm comprised of their external cell surface glycocalyx
      and by production of extracellular carbohydrate polymers. The adherent film is
      most difficult to remove. The accumulated planktonic phase can be reduced
      significantly by flushing water from the lines before use in patient treatment,
      but will return when the equipment is idle through the accumulation of more
      planktonic phase and by slough of the biofilm surface-adsorbed phase not yet
      enmeshed in the carbohydrate matrix. Chlorine dioxide has antimicrobial activity
      against many bacteria, spores, and viruses. It is used in water supply treatment
      as a disinfectant and slime preventive and has an advantage over chlorine in that
      carcinogenic trihalomethanes are not generated. METHODS: This study compared use
      of phosphate buffer-stabilized chlorine dioxide (0.1%) mouthrinse as a lavage in
      ultrasonic dental scaler units with the use of tap water as a control. Sterile
      water flushed through the units onto heterotrophic plate count (HPC) sampler
      plates was cultured 7 days at room temperature and colonies were counted at 12x.
      One test and one control unit were used for biopsy of internal tubing and
      scanning electron microscopy imaging. RESULTS: The HPC counts, in colony forming
      units (CFU)/ml, were reduced 3- to 5-fold by flushing tap water through the
      units, but they returned after units were idle overnight. When phosphate-buffered
      chlorine dioxide mouthrinse was used as a lavage, CFU/ml were reduced 12- to 20
      fold. Holding chlorine dioxide in waterlines overnight reduced recurrent buildup
      compared to water (P <0.05). Scanning electron microscopy images indicated a
      significant reduction of biofilm coverage by chlorine dioxide as compared to
      water (P<0.001). CONCLUSIONS: Phosphate-buffered chlorine dioxide mouthrinse was
      effective in these short-term trials for control of waterline contamination in
      ultrasonic dental scaling units. It should prove as useful in dental professional
      waterline applications as it has in industrial uses for biofilm control.

PMID- 11327070
TI  - Treatment of aggressive periodontitis by osseointegrated dental implants. A case
      report.
AB  - BACKGROUND: Generalized aggressive periodontitis is described as a clinical
      entity affecting both deciduous and permanent dentition with extensive alveolar
      bone loss, mobility, and exfoliation of all or many teeth. Controversy exists on
      dental implant use to restore missing dentition in younger patients. METHODS:
      This case report presents a patient diagnosed with aggressive periodontitis who
      has lost all but 4 of her teeth. Her personal and functional desires led us to
      include implant therapy in her treatment plan. The hematological data are
      presented with an analysis of the immunological profile. RESULTS: Dental implants
      were placed, and following 3 months of osseointegration, an implant-supported
      prosthesis was completed. The patient was followed up for 36 months. CONCLUSIONS:
      This case report presents an alternative treatment for rehabilitating dentition
      in a young patient treated for aggressive periodontitis. Similar case studies may
      help eliminate some of the controversy that exists regarding the use of dental
      implants in aggressive periodontitis patients.

PMID- 11327071
TI  - Two-stage versus one-stage--is there really a controversy?

PMID- 11327072
TI  - Re: A perspective on clinical significance. Hujoel PP, Armitage GC, Garcia RI
      (2000;71:1515-1518).

PMID- 11327074
TI  - [Diabetic foot].

PMID- 11327073
TI  - [Continuing education certificate Of the Bavarian Medical Society].

PMID- 11327075
TI  - Tachyphylaxis in 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors.

PMID- 11327076
TI  - High resolution ultrastructural reevaluation of dental cuticle in monkey tooth.
AB  - In this study the detailed ultrastructure of the dental cuticle at the
      dentogingival border in monkeys (macaques) was observed. The deciduous molars and
      permanent premolars with associated gingiva were prepared for thin section
      electron microscopy. The dental cuticle, seen as a dense amorphous, usually
      unlaminated layer, was localized between the tooth enamel and the junctional
      epithelium of the gingiva in close association with the internal basement
      membrane of the junctional epithelium. High resolution electron microscopy showed
      that its basic structure was a fine network of irregular anastomosing strands
      identified as the cord network of the basement membrane which was continuous with
      that of the lamina densa of the internal basement membrane of the junctional
      epithelium. In the cuticle. openings of most of the network were filled with a
      dark amorphous material. These observations suggest that an additional layer of a
      cord network formed from the basement membrane components, which is probably
      secreted by the cells of the junctional epithelium during formation of the
      cuticle, is added to the cord network of the lamina densa of the basement
      membrane. In addition, a dark amorphous material is deposited within the newly
      added cord network at the enamel side of the basement membrane. The origin of
      this dark material still remains to be clarified, but the possibility is that it
      originates, as has previously been suggested, from either serum protein in
      gingival exudate or from hemoglobin produced by the degradation of red blood
      cells.

PMID- 11327077
TI  - Antimicrobial activity of silver nitrate against periodontal pathogens.
AB  - Metal ions were evaluated as potential antimicrobial agents suitable for local
      delivery in the oral cavity for the treatment of periodontitis. Silver nitrate,
      copper chloride, and zinc chloride were tested for antimicrobial activity in in
      vitro killing assays conducted in phosphate buffered saline with a series of oral
      bacteria including gram-negative periodontal pathogens and gram-positive
      streptococci. Copper and zinc salts failed to exhibit strong and consistent
      activity against periodontal pathogens. In contrast, silver at a concentration of
      0.5 microg/mL produced a 3 log10 reduction in colony forming units (CFU)/mL or
      greater against all periodontal pathogens tested including Porphyromonas
      gingivalis, Prevotella intermedia, Prevotella denticola, Bacteroides forsythus,
      Fusobacterium nucleatum vincentii, Campylobacter gracilis, Campylobacter rectus,
      Eikenella corrodens, and Actinobacillus actinomycetemcomitans. In comparison,
      substantially higher concentrations of silver nitrate failed to kill oral
      streptococci. A silver nitrate concentration of 25 microg/mL produced log10
      reductions in CFU/mL of 3.5-5 in killing assays performed in human serum against
      P. gingivalis, demonstrating the ability of silver to retain activity in a
      biological medium similar to that encountered in vivo in the periodontal pocket.
      These results identify silver nitrate, an antimicrobial that may possess
      advantages over traditional antibiotics, as a potential agent for controlled
      release local delivery in the oral cavity for the treatment of periodontitis.

PMID- 11327078
TI  - Intraoral distribution of Actinobacillus actinomycetemcomitans in young adults
      with minimal periodontal disease.
AB  - The aim of the present study was to investigate the intraoral distribution of
      Actinobacillus actinomycetemcomitans in young adults with minor signs of
      periodontal disease but harboring the organisms in the oral cavity. 17 healthy
      volunteers, 20 to 27 years of age, participated. Samples from mucosal surfaces of
      the oro-pharyngeal cavity and saliva (n = 221) as well as subgingival plaque from
      every tooth (n =477) were selectively cultivated for A. actinomycetemcomitans.
      Species identity and presence of the leukotoxin encoding gene, ltxA, were checked
      by multiplex polymerase chain reaction. Moreover, the leukotoxin promoter region
      was analyzed. No isolate harbored a 530 bp deletion in the promoter region of the
      leukotoxin gene, signaling minimally toxic strains. 42.1 +/- 30.4%
      extracrevicular and 34.4 +/- 29.5% subgingival samples were culture-positive. In
      extracrevicular samples, the organism could easily be recovered from cheek mucosa
      (62%), saliva (59%) and the palatal tonsils (41%). Mean log-transformed numbers
      of A. actinomycetecomitans colony forming units (CFU/ml) in culture-positive
      material ranged between 1.8 from the hard palate and 2.3 from 10 microl saliva.
      The highest prevalence in subgingival plaque was observed at maxillary 3rd molars
      (55%) followed by maxillary lateral incisors (50%) and mandibular 3rd molars
      (41%). Mean log-transformed counts of CFU/ml ranged between 2.2 at maxillary 3rd
      molars and 3.4 at upper central incisors. When adjusted for jaw, site and tooth
      type, the odds of isolating higher numbers of the organism were increased with
      every mm probing depth by a factor of 1.35 (p <0.05). The odds ratio for bleeding
      on probing was 1.38. Thus, in this young adult population with minor periodontal
      disease, A. actinomyetemcomitans was mainly associated with some deviation from
      gingival health. Of concern might be a minority of subjects (29%) with an
      extremely wide distribution of the organism in the oral cavity.

PMID- 11327079
TI  - Involvement of cyclooxygenase-2 in serum-induced prostaglandin production by
      human oral gingival epithelial cells.
AB  - The purpose of the present study was to investigate the involvement of
      cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) in prostaglandin (PG)
      production by human oral gingival epithelial (OGE) cells stimulated with
      proinflammatory cytokines including interleukin(IL)-1alpha, IL-1alpha and tumor
      necrosis factor alpha (TNFalpha), and serum. Fetal bovine serum (FBS)-stimulated
      OGE cells produced significant levels of PGE2, whereas IL-1alpha, IL-1beta and
      TNFalpha could not induce significant PGE2 production. FBS induced PGE2
      production in a dose- and time-dependent manner. NS-398, a selective COX-2
      inhibitor, inhibited PGE2 production by FBS-stimulated cells as completely as
      indomethacin, a non-selective COX-1/COX-2 inhibitor. Expression of COX-2 protein
      in FBS-stimulated cells was increased, compared with that in unstimulated cells,
      whereas COX-1 protein expression was similar both in unstimulated and in FBS
      stimulated cells. COX-2 mRNA was detected in FBS-stimulated cells, but not in
      unstimulated cells. We suggest that COX-2 is responsible for PG production by
      human OGE cells stimulated with serum and that OGE cells may be involved in PG
      production in periodontal lesions. Selective COX-2 inhibitors, which have the
      advantage of reduced gastric toxicity, may provide a useful approach to treatment
      of periodontal disease.

PMID- 11327080
TI  - Basic fibroblast growth factor suppresses tropoelastin gene expression in
      cultured human periodontal fibroblasts.
AB  - Growth factors are known to play a major role in the regeneration of the
      periodontium. Basic fibroblast growth factor (bFGF) is a polypeptide growth
      factor considered to have a role in chemotaxis and mitogenesis of periodontal
      ligament (PDL) cells. The aim of this study was to assess the effect of bFGF on
      the transcription level of tropoelastin. As known controls, we assessed the
      transcription levels of collagen type I, collagen type II and the housekeeping
      gene, actin. Initially, PDL cells were cultured without bFGF for 3, 7 and 14
      days. At each time point. total RNA was extracted and the levels of transcription
      were assessed by semiquantitative reverse transcription polymerase chain reaction
      (RT-PCR) assay. The results showed that tropoelastin mRNA is transcribed in PDL
      cells and its levels increased from minimal amounts by day 3 to maximal amounts
      by day 14 of culture. We further examined the effect of the addition of 10 ng/ml
      bFGF to the culture media by day 14. The results showed that the addition of bFGF
      suppressed the transcription level of tropoelastin. At that time, as expected, a
      decrease in collagen type I transcription level was shown, while the
      transcription level of collagen type III was not affected. The findings that
      elastin is transcribed in vitro by PDL cells, but only negligibly in vivo, imply
      mechanisms that downregulate or even shut down the expression of the elastin gene
      in the functioning PDL. Basic FGF might be one of the cytokines involved in
      control of elastin expression in vivo.

PMID- 11327081
TI  - Phenotypic comparison of periodontal ligament cells in vivo and in vitro.
AB  - The mammalian periodontal ligament contains heterogeneous populations of
      connective tissue cells, the precise function of which is poorly understood.
      Despite close proximity to bone and the application of high amplitude physical
      forces, cells in the periodontal ligament (PL) are capable of expressing
      regulatory factors that maintain PL width during adult life. The study of PL
      homeostasis and PL cell differentiation requires culture and phenotypic methods
      for precise characterization of PL cell populations, in particular those cells
      with an inherently osteogenic program. Currently it is unknown if cells cultured
      from the PL are phenotypically similar to the parental cells that are present in
      the tissues. We have compared the phenotype of cells in vivo with cells derived
      from the PL and expanded in vitro to assess the general validity of in vitro
      models for the study of phenotypic regulation in vivo. Rat PL cells were isolated
      by either scraping the root of the extracted first mandibular molars (Group A),
      or by scraping the alveolar socket following extraction of first mandibular
      molars (Group B), or by obtaining a mixture of cells after disaggregating a block
      of tissue consisting of first mandibular molar, PL and the surrounding alveolar
      bone (Group C). Cultured cells at confluence were fixed and immunostained for
      alpha-smooth muscle actin (alpha-SMA), osteopontin (OPN), alkaline phosphatase
      (AP), or bone sialoprotein (BSP). For in vivo assessments, frontal sections of
      rat first mandibular molar were immunostained for alpha-SMA, OPN, AP and BSP. We
      examined osteogenic differentiation of cultured PL cell cultures by bone nodule
      forming assays. In vivo and at all examined sites, > 68% of PL cells were
      immunostained for AP; approximately 50% and approximately 51% for OPN and alpha
      SMA (p = 0.3), respectively, while only approximately 8% were positively stained
      for BSP (p < 0.01). Analysis of cultured PL cells in Groups A, B and C showed
      54%, 53%, and 56% positive staining for alpha-SMA respectively; 51%, 56%, 54% for
      OPN; 66%, 70%, 69% for AP and 2.2%, 1.4% and 2.8% for BSP. The mean percentage of
      PL cells in situ stained for the different markers was similar to that of
      cultured PL cells (Group A approximately Group B approximately Group C in situ
      for p > 0.2) except for BSP which was 3 to 4 fold higher in vitro (p < 0.01). PL
      cell cultures treated with dexamethasone showed mineralized tissue formation for
      all groups (A, B, C), but no mineralized tissue formation was detected in the
      absence of dexamethasone. As PL cells express quantitatively similar phenotypes
      in vitro and in vivo, we conclude that the in vitro models used here for
      assessment of PL cell differentiation appear to be appropriate and are
      independent of the cell sampling method. Further, dexamethasone-dependent
      progenitors are present both on the root and bone-related sides of the PL.

PMID- 11327082
TI  - Prostaglandin F2alpha upregulates interleukin-6 production in human gingival
      fibroblasts.
AB  - Prostaglandin F2alpha (PGF2alpha) is a bioactive lipid mediator which has been
      suggested to be involved in the pathogenesis of periodontal disease. However, the
      roles of PGF2alpha in periodontal lesions are poorly understood. In the present
      study, we investigated the effect of PGF2alpha on interleukin (IL)-6 production
      in human gingival fibroblasts (HGF). PGF2alpha stimulated IL-6 production in a
      time- and concentration-dependent fashion. IL-1beta and tumor necrosis factor
      alpha (TNFalpha), proinflammatory cytokines, induced IL-6 production in a time
      dependent manner, and PGF2alpha synergistically enhanced IL-6 production induced
      by IL-1beta and TNFalpha. IL-6 mRNA was expressed in PGF2alpha-stimulated HGF,
      and PGF2alpha increased IL-6 mRNA levels induced by IL-1beta and TNFalpha.
      Fluprostenol, a selective FP receptor agonist, could mimic PGF2alpha-induced IL-6
      production. Since FP receptors are coupled to elevation of intracellular calcium
      and activation of protein kinase C (PKC), the mechanism of IL-6 production by
      PGF2alpha was investigated using TMB-8, an inhibitor of Ca2+ mobilization from
      intracellular stores, and calphostin C, an inhibitor of PKC. TMB-8 significantly
      suppressed PGF2alpha-induced IL-6 production, whereas calphostin C showed a
      stimulatory effect on PGF2alpha-induced IL-6 production. From these data, we
      suggest that PGF2alpha upregulates IL-6 production through FP receptors in HGF,
      that PGF2alpha synergistically enhances IL-6 production in IL-1beta- and TNFalpha
      stimulated HGF, and that PGF2alpha-induced IL-6 production may be dependent on
      intracellular Ca2+ mobilization and be downregulated by PKC activation. PGF2alpha
      may be involved in the pathogenesis of periodontal disease by enhancing IL-6
      levels in periodontal lesions.

PMID- 11327083
TI  - Epidermal growth factor in saliva and serum of patients with cyclosporin-induced
      gingival overgrowth.
AB  - The purpose of this study was to investigate the presence of epidermal growth
      factor (EGF) in patients receiving cyclosporin therapy who had gingival
      overgrowth and to determine whether there were any differences between these
      patients and normal healthy controls. Seventeen patients with cyclosporin-induced
      gingival overgrowth and seventeen age- and sex-matched controls who were taking
      cyclosporin but had healthy gingiva were used for this study. Unstimulated whole
      saliva was collected from all individuals by expectoration. Gingival crevicular
      fluid (GCF) was also collected from all individuals. Blood was additionally
      collected from all subjects and serum was separated by keeping the samples
      overnight at 4 degrees C. EGF levels in all cases were measured by an ELISA
      assay. EGF concentrations were found to be significantly higher in the saliva of
      patients with cyclosporin-induced gingival overgrowth compared to the control
      group (401.2 +/- 31.1 pg/ml and 144.3 +/- 31.4 pg/ml, respectively), whereas the
      results were reversed in the serum (67.0 +/- 15.6 pg/ml and 141.6 +/- 17.7 pg/ml,
      respectively). EGF was not detected in the samples of GCF in either group. This
      study thus demonstrated an increase in EGF levels in the saliva and a decrease of
      EGF in the serum of patients with cyclosporin-induced gingival overgrowth.

PMID- 11327085
TI  - Endovaginal sonographic diagnosis of the fetal urinary tract anomalies in early
      pregnancy.
AB  - Transvaginal sonography has enhanced the ability to follow fetal development and
      detect pathologies in early gestation. Examination of the fetal urinary tract is
      an integral part of routine sonographic examinations in the second trimester of
      pregnancy and one of the major benefits of prenatal sonography is to allow early
      diagnosis of relatively common urinary tract malformations. Detailed evaluation
      of the fetal urinary tract and identification of anomalies were considered to be
      difficult before the 18th week of gestation prior to the use of transvaginal
      sonography. Using the transvaginal route, a detailed evaluation of the kidneys is
      possible around 12 weeks and structural anomalies of the urinary tract are being
      detected at an ever-increasing rate. Transvaginal sonography, owing to its
      proximity to the maternal pelvic organs, allows an earlier determination of the
      normal fetal urinary system and more accurate diagnosis and identification of
      fetal urinary anomalies as compared with transabdominal ultrasound.

PMID- 11327084
TI  - Costimulatory molecules in human periodontal disease tissues.
AB  - An immunoperoxidase technique was used to examine CD28, CD152, CD80 and CD86
      positive cells in gingival biopsies from 21 healthy/gingivitis and 26
      periodontitis subjects. The samples were placed into 3 groups (small,
      intermediate, large) according to the size of the infiltrate. The percent CD28+ T
      cells in the connective tissue infiltrates was highly variable with no
      differences between the healthy/gingivitis and periodontitis groups. While there
      was an increase in positive cells in intermediate infiltrates from both
      healthy/gingivitis (28.5%) and periodontitis (21.4%) patients compared with small
      infiltrates (8.6% and 11.8%, respectively), this was not significant, although
      the percent CD28+ T cells did increase significantly in tissues with increased
      proportions of B cells relative to T cells (p=0.047). A mean of less than 5%
      infiltrating T cells were CD152+ which was significantly lower than the mean
      percent CD28+ T cells in intermediate healthy/gingivitis lesions (p = 0.021). The
      mean percent CD80+ and CD86+ B cells and macrophages was 1-7% and 8-16%,
      respectively, the difference being significant in intermediate healthy/gingivitis
      tissues (p = 0.012). Analysis of these cells in relation to increasing numbers of
      B cells in proportion to T cells and also to macrophages, suggested that CD80 was
      expressed predominantly by macrophages while CD86 was expressed by both
      macrophages and B cells. Few endothelial cells expressed CD80 or CD86.
      Keratinocytes displayed cytoplasmic staining of CD80 rather than CD86 although
      the numbers of positive specimens in the healthy/gingivitis and periodontitis
      groups reduced with increasing inflammation. In conclusion, percentages of CD28,
      CD152, CD80 and CD86 did not reflect differences in clinical status. However, the
      percent CD28+ T cells increased with increasing size of infiltrate and with
      increasing proportions of B cells suggesting increased T/B cell interactions with
      increasing inflammation. The percent CD152+ cells remained low indicating that
      CD152 may not be involved in negative regulation of T cells in periodontal
      disease. CD80 and CD86 have been reported to promote Th1 and Th2 responses,
      respectively, and the higher percent CD86+ cells suggests a predominance of Th2
      responses in both healthy/gingivitis and periodontitis tissues. Nevertheless,
      other factors including cytokines themselves and chemokines which modulate T cell
      cytokine profiles must be monitored to determine the nature of Th1/Th2 responses
      in periodontal disease.

PMID- 11327086
TI  - The diagnosis of bacterial vaginosis and vaginal flora changes.
AB  - In a population of 956 women, attending for contraceptive advice, 131 (13.7%)
      were found to have BV acording to Amsel's criteria. Clue cells were detected in
      200 (20.9%) women, a positive amine ('sniff') test in 191 (20.0%), a vaginal pH >
      or = 4.7 in 243 (25.4%) and a "characteristic" vaginal discharge in 104 (10.9%)
      women. Sensitivity, specificity, positive and negative predictive values in
      relation to BV were calculated for each of these four criteria. The detection of
      clue cells, an increased pH and a positive sniff test showed excellent
      sensitivity (86-100%) values, but had a less satisfactory positive predictive
      value (52-68%). Vaginal discharge was found to be a poor predictor of BV. The
      vaginal flora in women with clue cells, increased vaginal pH or a positive sniff
      test was very similar to that of the women with BV, every after excluding
      concomitant cases of BV and the three respective criteria. Thus, a positive amine
      test, which is easily performed, strongly suggests BV and a vaginal flora
      predominated by Gardnerella vaginalis, Mycoplasma hominis, Mobiluncus species and
      anaerobic species on one hand, and lack of lactobacilli on the other. When there
      is a clinical suspicion of BV, the sniff test is positive and differential
      diagnoses are excluded, one can safely treat a woman for bacterial vaginosis.

PMID- 11327087
TI  - Assessment of endocrine status in patients undergoing in-vitro fertilization
      treatment. Is it necessary?
AB  - Endocrine evaluation as a prerequisite for every patient undergoing routine in
      vitro fertilization (IVF) and embryo transfer for tubal or male factor
      infertility is still a matter of debate. The aim of this study was to determine
      if a full endocrine work-up, including the measurement of androgens,
      gonadotropins, prolactin and TSH, is conclusive for the subsequent success in
      IVF/ET. 71 infertile women without known endocrinopathies (e.g., polycystic
      ovarian disease), who were scheduled to enter the IVF/ET program were studied
      under strictly standardized conditions during the follicular phase of a natural
      cycle. Fasting serum concentrations of follicle stimulating hormone, luteinizing
      hormone, oestradiol, progesterone, prolactin, testosterone (T),
      dehydroepiandrosterone, 17-OH-progesterone, androstenedione and thyroid
      stimulating hormone (TSH) were measured using commercially available
      radioimmunoassays. Ovarian stimulation was performed by a long gonadotrophin
      releasing hormone agonist/human menopausal gonadotrophin protocol. The overall
      clinical pregnancy rate was 15.5% in the first started IVF cycle. While patients
      who conceived in the first treatment cycle had significantly lower T levels (368
      +/- 49 pg/ml) than those who did not (518 +/- 27 pg/ml, p=0.042, Kruskal & Wallis
      H-test), but the percentage of women with elevated T concentrations was not
      different. Similarly, TSH concentrations were significantly higher in women with
      a clinical pregnancy (1.9 +/- 0.2 mU/ml) than in non-pregnant women (1.4 +/- 0.3
      mU/ml, p=0.046), but levels were still within the normal range. There were no
      further significant differences in hormone levels between pregnant and non
      pregnant patients. These results do not suggest the measurement of a full
      hormonal profile in all infertile women before IVF/ET in non-endocrine
      infertility, taking into account the low likelihood to identify endocrinological
      disturbances, the considerable cost of endocrine testing and the paucity of
      therapeutic consequences.

PMID- 11327088
TI  - Sacrospinous ligament fixation for vaginal vault prolapse.
AB  - INTRODUCTION: To assess intra- and postoperative complications and to look for
      long term follow-up results in women with sacrospinous ligament fixation.
      METHODS: Between 1988 and 1999, 200 women (mean age 59.8 years, range 33 to 83
      years) underwent vaginal unilateral sacrospinous ligament fixation. 172 patients
      had had prior hysterectomy. In 28 patients concomitant hysterectomy and
      sacrospinous ligament fixation was performed. Sacrospinous ligament fixation was
      combined with the following procedures: 109 enterocele repairs (54.5%), 88
      anterior colporrhaphies (44%), 57 reconstructions of urogenital diaphragma
      (28.5%) and 23 posterior colporrhaphies (11.5%). Additional Burch colposuspension
      and a Stamey procedure were carried out in 7 (3.5%) and 15 (7.5%) patients,
      respectively. RESULTS: All 200 patients were analysed for intra- and
      postoperative complications. Urinary tract infection (n = 16, 8.0%), temporary
      irritation of the sciatic nerve (n = 15, 7.5%), temporary partial ureteral
      obstruction (n = 11, 5.5%) and blood loss less than 400 ml (n = 7, 3.5%),
      occurred in the postoperative phase. Long-term data (range from 6 months to 9
      years, mean 4.8 years) exist for 123 patients. 119 were completely cured without
      any signs of urinary incontinence and prolapse. At follow-up 4 patients (3.25%)
      showed recurrent vaginal vault prolapse. Recurrent cystoceles, rectoceles,
      enteroceles, were found in 10 cases (8.1%), one (0.8%) and one (0.8%),
      respectively. Two patients with complete recurrence of vaginal vault prolapse
      successfully underwent colpectomy and repeated sacrospinous ligament fixation,
      respectively. CONCLUSIONS. Sacrospinous ligament fixation is an effective and
      safe procedure with a low recurrence and complication rate.

PMID- 11327089
TI  - Obstetric outcome of teenage pregnancies in North Jordan.
AB  - OBJECTIVE: The purpose of this study was to investigate obstetric outcomes of
      nulliparous teenagers and to compare selected variables of their course and
      outcome of pregnancy with controls. METHODS: A review of hospital records from
      1997-1999 was done to compare the obstetric outcome in 760 teenage first
      pregnancies (study group) with that in control group i.e. 20 years to 29 years
      selected from the first women in the birth registry who delivered after each
      study case and satisfying the criteria for controls. RESULTS: Revealed that
      incidence of complications of pregnancy like anemia, pregnancy induced
      hypertension and antepartum hemorrhage were similar in study and control groups.
      Pregnancy weight gain, prelabour rupture of membranes and gestational diabetes
      were significantly lower among teenage mothers. The normal mode of delivery was
      commoner in teenagers (89.5%) in comparison to control group (72%), probably
      because of higher number of low birthweight babies. Although in study group the
      mean birthweight was lower and the incidence of preterm labour and small for
      gestational age infants higher, there was also increased incidence of large for
      gestational age infants. While there was no difference in the types of labour,
      there were lower caesarean and instrumental deliveries. A statistically non
      significant higher incidence of perinatal deaths was observed in teenagers.
      CONCLUSIONS: These results indicated that the course and outcome of pregnancy in
      teenage mothers had in most respects better obstetric outcomes, despite the
      higher incidence of preterm labour.

PMID- 11327090
TI  - Pregnancy outcome at age 40 and older.
AB  - OBJECTIVE: Our purpose was to examine pregnancy outcomes among women age 40 or
      older. METHODS: Between January, 1997 and December 1999, we performed a case
      control study compared pregnancy outcomes of 468 patients delivered at our
      hospital at > Or = 40 years old with outcomes in a control group consisting of
      the next two deliveries of women with ages 20 to 29 years. Retrospective analysis
      of the antepartum and intrapartum records was done to compare clinical outcome.
      RESULTS: Approximately 25,356 women delivered during the study period, and 468
      (1.8%). Of these women were at age 40 or older. Of this latter group, 50 (10.7%)
      were nulliparous. Mean birthweight of infants delivered by older nulliparous
      women was significantly lower than that among nulliparous controls (3,210 +/- 5
      vs. 3,320 +/- 1 g), whereas mean birth weight in the group of older multiparous
      was not different than that among younger multiparous controls (3,370 +/- 1 vs.
      3,365 +/- 4 g). Gestational age at delivery was significantly lower among older
      nulliparous, and multiparous compared with nulliparous and multiparous younger
      controls. Older women were at increased risk for cesarean delivery (nulliparous
      18%; multiparous 14%) compared with nulliparous and multiparous younger control
      groups (nulliparous 8%; multiparous 6%). In the study group, the operative
      vaginal delivery rate was higher than that of the control group. The study groups
      were more likely to develop gestational diabetes, preeclampsia, and placenta
      praevia. Older nulliparous had an increased incidence of malpresentation,
      abnormal labour patterns, special care baby unit admission (SCBU), and low 1
      minute Apgar score. Older multiparous were more likely to experience birth
      asphyxia, premature rupture of membranes, and antepartum vaginal bleeding.
      CONCLUSION: Nulliparous women age 40 or over have a higher risk of operative
      delivery than do younger nulliparous women. This increase occurs in spite of
      lower birth weight and gestational age and may be explained by the increase
      incidence of obstetric complications. Although maternal morbidity was increased
      in the older women, the overall neonatal outcome did not appear to be affected.

PMID- 11327091
TI  - Comparative pharmacokinetics of once daily intravenous and intramuscular
      gentamicin in patients with post partum endometritis.
AB  - In patients with post partum endometritis once daily intramuscular administration
      of gentamicin may be convenient in certain clinical settings. However
      pharmacokinetic data on once daily intramuscular gentamicin are not reported. In
      this study 10 women with post partum endometritis were given once daily
      intravenous gentamicin (4 mg/kg ideal body weight) followed at a later day by a
      similar intramuscular dose. Gentamicin levels coincided at 30 min. Levels at 60
      and 90 min were lower with the intravenous route. Further clinical studies are
      needed to confirm reduced nephrotoxicity and ototxicity with the intramuscular
      route.

PMID- 11327092
TI  - Prognostic influence  of delays between exploratory and definitive laparotomy in
      the treatment of malignant ovarian tumors.
AB  - BACKGROUND: The aim of this retrospective study was to evaluate whether a delay
      between a preliminary exploratory laparotomy and a definitive staging laparotomy
      and interval chemotherapy between the two operations affected the prognosis of
      ovarian cancer. METHODS: Of 504 patients with malignant tumors of the ovary who
      were treated at the Department of Obstetrics and Gynecology between 1980 and
      1993, there were 24 who had a delayed definitive staging laparotomy. RESULTS:
      Sixteen patients did not have chemotherapy between their two operations. After
      definitive laparotomy, 13 patients (54.2%) were free of disease and 11 patients
      had residual disease (45.8%). CONCLUSIONS: The value of chemotherapy between
      preliminary and definitive laparotomy in halting tumor growth was not
      demonstrated by the results of our analysis.

PMID- 11327093
TI  - Cytokine profiles in autologous peritoneal fluid and peripheral blood of women
      with deep and superficial endometriosis.
AB  - In a preliminary study the hypothesis was tested that cytokine profiles in
      peripheral blood were higher in women with deep infiltrating endometriosis and
      cytokine profiles in peritoneal fluid were higher in women with superficial
      endometriosis. Thirteen women of reproductive age having laparoscopy for
      infertility (n=9), pain (n=3) or combined pain and infertility (n=1). Peripheral
      blood and peritoneal fluid were obtained and analyzed for Interleukin-6 (IL-6),
      Tumor Necrosis Factor-alpha (TNF-alpha), Interleukin-10 (IL-10), Transforming
      Growth Factor-betal (TGFbeta1), and Interferon-gamma (IFN-gamma). No significant
      cytokine differences were observed in either peritoneal fluid or peripheral blood
      between IL-6, TGFbeta1, IFNgamma, TNF-alpha and IL-10 of women with superficial
      endometriosis (n=7) and women with deeply infiltrating endometriosis (n=6). The
      results of this preliminary study do not show significant differences in
      peripheral blood and peritoneal fluid cytokine levels between women with deep
      infiltrating endometriosis compared to women with superficial disease. Future
      studies with increased sample size are required to either confirm or refute these
      preliminary findings.

PMID- 11327094
TI  - Altered mRNA expression of ecNOS and iNOS in myometrium and placenta from women
      with preeclampsia.
AB  - OBJECTIVE: Preeclampsia is a syndrome involving dysfunction of vascular
      endothelium and imbalance between endothelium derived constricting and relaxing
      factors. Recent evidence suggests that endothelium-derived nitric oxide (NO)
      plays a role in the regulation of vascular resistance during normal pregnancy and
      preeclampsia. NO is a potent vasodilator and is generated by the catalytic action
      of nitric oxide synthases ecNOS and iNOS in myometrium and placenta. METHODS: In
      this study mRNA expressions of ecNOS and iNOS were compared in myometrium and
      placenta. Biopsies were collected from women with preeclampsia (n=8) and normal
      pregnancies (n=12). ecNOS and iNOS mRNA levels were determined using RT-PCR and
      expressed as arbitrary units after correction for control GAPDH gene mRNA levels.
      RESULTS: The mRNA expression of ecNOS was significantly higher in both myometrium
      (p<0.05) and placenta (p<0.05) from women with preeclampsia compared to that in
      normal pregnancies, while the iNOS mRNA level was not altered in myometrium and
      lower in placenta (p<0.05) from women with preeclampsia. CONCLUSIONS: The higher
      ecNOS mRNA expression might be a compensatory response to an impaired
      vasodilatation in the uteroplacental circulation during preeclampsia. Whether the
      similar and reduced levels of iNOS mRNA expression in myometrium and placenta,
      respectively, in women with preeclampsia is of importance remains to be further
      evaluated.

PMID- 11327095
TI  - Combined intrauterine and extrauterine gestation. A rare cause of acute abdominal
      pain.
AB  - This is the report of a patient, that had without using any assisted reproduction
      technology (ART) the rare event of a heterotopic pregnancy. After verifying the
      intrauterine pregnancy by ultrasound, the ectopic tubal pregnancy (EP) was
      detected at an emergency abdominal surgery as the cause of an intraabdominal
      hemorrhage. After removal the further pregnancy was uncomplicated.

PMID- 11327096
TI  - Successful treatment of primary fetal hydrothorax with hydrops by pleuroamniotic
      shunt placement.
AB  - We treated a case of primary fetal hydrothorax with hydrops. A pleuroamniotic
      shunt catheter inserted at 30 weeks accomplished resolution of hydrops and was
      maintained until cesarean delivery at 34 weeks with no need for further prenatal
      intervention. At age 9 months, the infant showed no effusion or pulmonary
      compromise.

PMID- 11327097
TI  - Abnormal vaginal bleeding as first symptom of acute leukemia.
AB  - We report a case of a 37-year-old woman, presenting with vaginal hemorrhage,
      together with severe anemia and thrombocytopenia (hematocrit: 10.6%; platelets: 6
      G/l) caused by previously unknown acute lymphocytic leukemia.

PMID- 11327098
TI  - Predictive value of human chorionic gonadotrophin beta-hCG in early pregnancy
      after assisted conception.
AB  - OBJECTIVE: This study was designed to evaluate the predictive value of beta-hCG
      levels in predicting the pregnancy outcome. METHODS: A retrospective analysis was
      done on 423 pregnant patients following assisted conception (stimulated in vitro
      fertilization [SIVF] and stimulated intra uterine insemination [SIUI]). These
      were monitored with plasma beta-hCG on day +18 post hCG injection. Ongoing
      pregnancy was defined as greater than 20 weeks. RESULTS: Four hundred twenty
      three patients had a positive serum quantitative beta-hCG level 18 days post hCG
      injection. Of these 321 (75.9%) were ongoing pregnancies. The spontaneous
      miscarriages were 98 (23.2%), and four ectopic pregnancies were recorded. Of the
      successful pregnancies, 279 were single births, and 42 were multiple births
      (15.1%), that is either twins (31) or triplets (11). Tables were calculated to
      help predicting the pregnancy outcome. CONCLUSIONS: It can be shown that +18
      levels of beta-hCG in cases of assisted conception are useful and provide
      predictive information concerning pregnancy outcome which should be helpful for
      the staff and the infertility patients.

PMID- 11327099
TI  - Obesity, low for gestational age birth weight, and subsequent cardiovascular
      risk.

PMID- 11327100
TI  - The renin-angiotensin system and natriuretic peptides in obesity-associated
      hypertension.
AB  - Excessive accumulation of adipose tissue is associated with profound alterations
      in the cardiovascular system. including an increase in systemic blood pressure.
      It now appears clear that a central feature of obesity-associated hypertension is
      related to changes in sodium handling that may result from abnormalities in
      sympathetic nervous system activity, the renin-angiotensin-aldosterone system,
      natriuretic peptides, and kidney function. In this paper we review the role of
      these factors in the development of obesity-associated hypertension, thereby
      focusing on the potential role of adipose tissue in these alterations.

PMID- 11327101
TI  - The pleiotropic functions of peroxisome proliferator-activated receptor gamma.
AB  - Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone
      receptors, initially described as molecular targets for synthetic compounds that
      induce peroxisome proliferation. PPARgamma is the best characterized of the
      PPARs. The heterodimer of PPARgamma with the retinoid X receptor (RXR) plays a
      crucial role in adipogenesis and insulin sensitization. The RXR/PPARgamma
      heterodimer furthermore has been reported to have important immunomodulatory
      activities and to affect cell proliferation/differentiation pathways in various
      malignancies. PPARgamma is activated by a number of naturally occurring fatty
      acid derivatives and by several synthetic compounds, including the
      thiazolidinediones and L-tyrosine-based insulin sensitizers. This review gives an
      overview of the pleiotropic functions of PPARgamma and discusses the wide-ranging
      medical implications that modulation of PPARgamma activity might have for various
      diseases, ranging from obesity and type 2 diabetes to cancer and inflammation.

PMID- 11327102
TI  - On nerve regeneration with the application of the suture. 1865.

PMID- 11327103
TI  - Genetic and physiological analysis of the role of uncoupling proteins in human
      energy homeostasis.
AB  - The metabolic utilization of substrates results in ATP synthesis and energy loss
      as heat. In tissues and cells the mitochondria reoxidize reduced coenzymes and
      phosphorylate ADP. A significant proportion of the energy is released through
      thermogenesis by mitochondria. This is due to a less than perfect coupling of
      cellular respiration to ATP synthesis. Previous studies of brown adipocytes,
      which are cells specialized in regulatory thermogenesis, have shown that heat
      production is due to the regulated activity and synthesis of a particular proton
      transporter in the inner membrane of brown adipocyte mitochondria--uncoupling
      protein (UCP) 1. UCP homologues have recently been identified. UCP2 is widely
      expressed in human tissues, whereas UCP3 is expressed predominantly in human
      skeletal muscles. These novel UCPs represent genes which are potentially
      important for regulation of metabolic pathways and energy expenditure in humans.
      Biochemical and genetic studies support a role for these novel UCPs in metabolic
      regulations in humans. However, several physiological studies question such a
      role. Importantly, UCP2 and UCP3 seem to be able to control the activity of
      mitochondria in response to oxidants.

PMID- 11327104
TI  - Searching for genes underlying normal variation in human adiposity.
AB  - A primary challenge in biomedical research today is the elucidation of the
      underlying genetic architecture of complex conditions such as obesity. In
      contrast to simple Mendelian disorders that result from a mutation in a single
      gene, complex phenotypes are the product of the action (as well as interaction)
      of multiple genes and environmental factors. The genetic configuration of these
      genes can range from effectively polygenic (i.e., many genes each with a
      relatively small contribution) to oligogenic (i.e., a few genes with relatively
      large measurable effects often expressed on a residual additive genetic
      background). While the task at hand is complicated, it is not intractable;
      however, it does require consideration of the nature of the disease and
      definition of its associated phenotypes in selecting the most appropriate study
      design. Here we will discuss the characteristics of obesity and its related
      phenotypes, which must be considered in designing analyses to identify the genes
      involved as well as reviewing what these approaches have provided in the search
      for genes influencing adiposity in humans

PMID- 11327105
TI  - Obesity: the dire consequences of a genetic program for survival?

PMID- 11327106
TI  - Regulation of leptin production: sympathetic nervous system interactions.
AB  - Leptin is secreted primarily from white adipose tissue and stimulates long-form
      OB-Rb receptors in the hypothalamus to decrease food intake and increase energy
      expenditure. A variety of neuropeptides are involved in these responses,
      including neuropeptide Y, agouti-related protein, the prepro-melanocortin system
      and cocaine- and amphetamine-regulated transcript. OB-Rb receptors (and other
      receptor isoforms) are also found in peripheral tissues. Leptin is now known to
      have a wide range of peripheral actions and is involved in activating the immune
      system, haematopoiesis, angiogenesis and as a growth factor, as well as being a
      regulator of many cellular functions. The identification of leptin has led to
      reappraisal of the role of white adipose tissue from being an organ concerned
      primarily with energy storage as fat to an understanding that it is also a major
      endocrine and secretory organ. While the importance of the sympathetic nervous
      system in mobilising fatty acids from adipose tissue has long been known, it has
      become apparent that the sympathetic system is a key regulator of leptin
      production in white adipose tissue as well. Sympathomimetic amines and cold
      exposure or fasting (which lead to sympathetic stimulation of white fat),
      decrease leptin gene expression in the tissue and leptin production. On the other
      hand, sympathetic blockade often increases circulating leptin and leptin gene
      expression, and it is possible that the sympathetic system has a tonic inhibitory
      action on leptin synthesis. Apart from the few instances where leptin is absent,
      leptin levels are increased in obesity, while the sympathetic sensitivity of
      adipose tissue is reduced, consistent with the high leptin levels that are seen.
      The dysregulation of energy balance leading to obesity may partly involve a
      decrease in leptin sensitivity, or the leptin system may be set to have maximal
      effects at low leptin levels.

PMID- 11327107
TI  - Antifouling activities of octocorals on some marine microfoulers.
AB  - The antifouling activities of vacuum-dried 70% aqueous alcohol extracts of four
      gorgonian and five soft corals against four dominant marine fouling diatoms
      (Navicula subinflata Grun, N. crucicula Smith, Amphora sp., Nitzschia sp.) are
      described. Of the 36 possible combinations (9 corals x 4 diatoms) 23 of the
      interactions (64%) showed 100% activity. Extracts of the gorgonian coral
      Echinogorgia complexa Nutting and the soft coral Dendronephthya (Morchellana) sp.
      showed 100% growth inhibition against all four fouling diatoms, implying the
      presence of potent broad spectrum antifouling compounds; other extracts showed
      more limited species specificity. Exposed cells when transferred to extract-free
      media, resumed normal growth indicating a nontoxic way of action. The effective
      concentration for 50% growth inhibition of the attached cells (EC50) varied for
      each extract and test organism used. The EC50 values for the extract of the
      gorgonian coral E. complexa against the fouling diatoms ranged from 86 microg/ml
      (N. subinflata) to 505 microg/ml (Amphora sp.) whereas the EC50 values for
      extracts of the soft coral Dendronephthya (Morchellana) sp. varied from 28
      microg/ml (N. crucicula) to 415 microg/ml (Amphora sp.). The results support the
      hypothesis that octocorals contain antifouling agents, which could be exploited
      for the development of nontoxic natural antifouling technology.

PMID- 11327108
TI  - In vitro antibacterial activity of glass-ionomer cements.
AB  - The in vitro antibacterial activity of the glass-ionomer restorative cements
      Ketac-Cem, Ketac-Bond, Ketac-Silver and Vitrebond was studied in conjunction with
      32 strains of five bacteria involved in the development of caries: Streptococcus
      spp., Lactobacillus spp., Actinomyces spp., Porphyromonas spp. and Clostridium
      spp. The agar plate diffusion method was used for the cultures, which included a
      chlorhexidine positive control. All the glass-ionomer cements tested inhibited
      bacterial growth, but with considerable differences in the scope of their action.
      Of the four cements, Vitrebond, a resin-modified glass-ionomer cement, was
      determined to be the most effective bacterial inhibitor.

PMID- 11327109
TI  - A simple classification method for residual antibiotics using E. coli cells
      transformed by the calcium chloride method and drug resistance plasmid DNA.
AB  - Using three different plasmid DNA codings for kanamycin (KM), chloramphenicol
      (CP), and ampicillin- (AMP) and tetracycline- (TC) resistance, four different
      competent Escherichia coli strains were transformed by the calcium chloride
      method to produce KM-, CP- and AMP- and TC-resistant strains. Evaluation of
      minimum inhibitory concentrations (MIC) of 22 antibiotics, showed KM-resistant E.
      coli to be cross resistant only to fradiomycin (FRM); CP-resistant E. coli,
      especially HB101 and JM109 strains, exhibited cross-resistance only to
      thiamphenicol (TP). On the other hand, AMP- and TC-resistant E. coli showed cross
      resistance to several penicillins, tetracyclines and erythromycin. E. coli ATCC
      27166, the strain most sensitive to all drugs in this experiment, was employed
      for disc diffusion experiments and from the pattern of appearance of the
      inhibition zone, eight major antibiotics were divided into three groups depending
      on their activity against containing each of the three plasmids. Only gentamicin
      (GM) activity was not affected by any of the drug resistant strains. Assay
      techniques utilizing three resistant strains may be the technique for screening
      foods for antibiotic residues in the future.

PMID- 11327110
TI  - Microbial contamination of water-soaked cotton gauze and its cause.
AB  - Seven in-use cotton gauze samples and three cotton balls soaked in sterile
      distilled water in canisters were investigated 7 days after they were prepared in
      hospital. All samples were contaminated with bacteria including 10(6) to 10(7)
      colony forming units/ml of Pseudomonas aeruginosa. In vitro viability tests using
      cotton gauze and cotton balls soaked in sterile distilled water revealed rapid
      proliferation of P. aeruginosa, Serratia marcescens and Candida albicans. Since
      the cotton gauze and the cotton balls were soaked in water containing nutrients,
      such as protein and glucose, these materials may be readily contaminated with
      bacteria including P. aeruginosa. Thus, when using cotton gauze and cotton balls
      containing water, microbial contamination should be expected.

PMID- 11327111
TI  - Acid tolerance of Escherichia coli O157:H7 and its survival in apple juice.
AB  - Outbreaks of diarrhoea and haemolytic uraemic syndrome have been associated with
      the consumption of apple cider and apple juice. The organism implicated in these
      outbreaks has been Escherichia coli O157:H7, indicating the resistance of the
      serotype to acidic pH. On comparing the growth of this serotype with a control
      strain of E. coli, it was found that strain O157:H7 grew well in trypticase soy
      broth at pH levels ranging from 2.0 to 9.0, while control strains failed to grow
      at pH levels below 4.0 and above 9.0. The growth of both strains were inhibited
      by adding 0.05% of either benzoic acid or sorbic acid. Similarly, O157:H7 grew
      well in both natural (unpasteurized) as well as in pasteurized apple juice and
      the growth was inhibited by adding 0.1% of either benzoic acid or sorbic acid.
      Control strains of E. coli failed to grow in either types of apple juice. The
      possible sources of contamination of natural apple juice with O157:H7 serotype
      are discussed.

PMID- 11327112
TI  - Polyamines of the thermophilic eubacteria belonging to the genera Thermosipho,
      Thermaerobacter and Caldicellulosiruptor.
AB  - Cellular polyamines of four new thermophiles located in three early branched
      eubacterial clades, were investigated for the chemotaxonomic significance of
      polyamine distribution profiles. The thermophilic anaerobic Thermosipho
      japonicus, belonging to the order Thermotogales, contained norspermidine,
      norspermine and thermospermine in addition to spermidine and spermine. The
      polyamine profile was identical to the polyamine composition of Thermotoga,
      Fervidobacterium and Petrotoga species of the order. Spermidine, norspermidine,
      spermine, N4-bis(aminopropyl)spermidine and agmatine were found in thermophilic
      aerobic Thermaerobacter marianensis. Some differences were observed in the
      polyamine compositions of the phylogenetically related thermophilic anaerobes,
      Moorella, Dictyoglomus, Thermoanaerobacterium and Thermoanaerobacter species.
      Thermophilic anaerobic Caldicellulosiruptor kristianssonii and
      Caldicellulosiruptor owensensis contained a linear penta-amine, thermopentamine,
      and two quaternary branched penta-amines, N4-bis(aminopropyl)spermidine and N4
      bis(aminopropyl)norspermidine, as the major polyamines. A novel tertiary branched
      penta-amine, N4-aminopropylspermine, was found in the two Caldicellulosiruptor
      species.

PMID- 11327113
TI  - Circulating immune complexes induced by food proteins implicated in precocious
      myocardial infarction.
AB  - BACKGROUND: Circulating immune complexes (CIC) are frequently found in
      postinfarction patients. The constituents of these CIC are mostly unknown. AIM:
      The objective of the current study was to assess whether CIC containing
      alimentary proteins and antibodies against these proteins are implicated in
      precocious myocardial infarction (MI). METHODS: Seventy-six survivors (67 men and
      9 women, mean age 39 years) of a first MI before the age of 45 years were
      enrolled in this study. Two control groups were included. One group consisted of
      age-matched, randomly selected, population-based healthy individuals, 79 men and
      11 women, without features of coronary heart disease. An additional control group
      was used only for the determination of serum antibodies against some of the
      alimentary proteins and consisted of 139 healthy blood donors, 95 men and 44
      women, with a mean age of 42 years. Sucrose density gradient centrifugation, gel
      filtration and precipitation by polyethylene glycol were used for the isolation
      of CIC, and enzyme-linked immunosorbent assay (ELISA) was used to measure the
      immunoglobulin levels and specific antibodies against alimentary proteins in both
      sera and isolated CIC. Sodium dodecylsulfate (SDS) polyacrylamide gel
      electrophoresis and Western blotting were used to determine alimentary proteins
      in the CIC. RESULTS: Alimentary antigens/antibodies were present in immune
      complex form in seven out of 14 (50%) postinfarction patients who had persistent
      high concentrations of CIC, the latter constituting 18% of the entire group.
      Antibodies of the IgG isotype predominated. A rise in CIC, signs of activation of
      the classical complement pathway, and a rise in plasma concentrations of von
      Willebrand factor antigen (vWFAg) were evident within 1 week in four patients
      subjected to a 2-week elimination diet followed by a single challenge with cow's
      milk. CONCLUSION: This study suggests that dietary proteins occasionally give
      rise to persistent CIC, which may predispose to MI at a young age.

PMID- 11327114
TI  - Checkpoint genes in cancer.
AB  - The mammalian cell cycle is exquisitely controlled by a 'machinery' composed of
      cyclin-dependent kinases and their binding partners, the cyclins. These kinases
      regulate transitions into DNA synthesis and mitosis, and their inactivity
      contributes to cellular quiescence, differentiation and senescence. Cell cycle
      transitions are, in turn, controlled by checkpoints that monitor ribonucleotide
      pools, oxygen tension, the extracellular environment, growth signalling
      programmes, the status of DNA replication, and the mitotic spindle apparatus.
      Genes positively controlling cell cycle checkpoints can be targets for oncogenic
      activation in cancer, whereas negative regulators, such as tumour suppressor
      genes, are targeted for inactivation. Understanding the molecular details of cell
      cycle regulation and checkpoint abnormalities in cancer offers insight into
      potential therapeutic strategies.

PMID- 11327115
TI  - Telomerase activation, cellular immortalization and cancer.
AB  - The maintenance of specialized nucleoprotein structures termed telomeres is
      essential for chromosome stability. Without new synthesis of telomeres at
      chromosome ends the chromosomes shorten with progressive cell division,
      eventually triggering either replicative senescence or apoptosis when telomere
      length becomes critically short. The regulation of telomerase activity in human
      cells plays a significant role in the development of cancer. Telomerase is
      tightly repressed in the vast majority of normal human somatic cells but becomes
      activated during cellular immortalization and in cancers. While the mechanisms
      for telomerase activation in cancers have not been fully defined, they include
      telomerase catalytic subunit gene (hTERT) amplification and trans-activation of
      the hTERT promoter by the myc oncogene product. Ectopic expression of hTERT is
      sufficient to restore telomerase activity in cells that lack the enzyme and can
      immortalize many cell types. Understanding telomerase biology will eventually
      lead to several clinically relevant telomerase-based therapies. These
      applications include inhibiting or targeting telomerase as a novel antineoplastic
      strategy and using cells immortalized by telomerase for therapeutic applications.

PMID- 11327116
TI  - Molecular genetics of prostate cancer.
AB  - The molecular mechanisms underlying the development and progression of prostate
      cancer are poorly understood. Epidemiological studies have suggested that 5-10%
      of all prostate cancers are familial, and numerous chromosomal loci have been
      associated with prostate cancer in multicentre linkage studies. However, no
      putative susceptibility genes harboured in these chromosomal regions have thus
      far been identified. Several recurrent chromosomal alterations in prostate cancer
      have been detected in comparative genomic hybridization (CGH) and loss of
      heterozygosity (LOH) analysis. The target genes for many of these aberrations are
      still not known. It seems that the androgen receptor (AR) signalling pathway
      plays a crucial role in both early development as well as in late progression of
      the disease. Both germ-line and somatic genetic alterations in the AR gene have
      been demonstrated in prostate cancer patients. The intention of this review is to
      summarize the current knowledge of molecular mechanisms in the development of
      prostate cancer.

PMID- 11327117
TI  - Biochip technologies in cancer research.
AB  - Development of high-throughput 'biochip' technologies has dramatically enhanced
      our ability to study biology and explore the molecular basis of disease. Biochips
      enable massively parallel molecular analyses to be carried out in a miniaturized
      format with a very high throughput. This review will highlight applications of
      the various biochip technologies in cancer research, including analysis of 1)
      disease predisposition by using single-nucleotide polymorphism (SNP) microarrays,
      2) global gene expression patterns by cDNA microarrays, 3) concentrations,
      functional activities or interactions of proteins with proteomic biochips, and 4)
      cell types or tissues as well as clinical endpoints associated with molecular
      targets by using tissue microarrays. One can predict that individual cancer risks
      can, in the future, be estimated accurately by a microarray profile of multiple
      SNPs in critical genes. Diagnostics of cancer will be facilitated by biochip
      readout of activity levels of thousands of genes and proteins. Biochip
      diagnostics coupled with informatics solutions will form the basis of
      individualized treatment decisions for cancer patients.

PMID- 11327118
TI  - Talking tumours: histories from sequences.
AB  - The history of a tumour is currently inferred from its morphology. However,
      progression may be variable between similar appearing tumours, and some critical
      events may be difficult to see. It has become increasingly apparent that
      histories are also written within sequences. Every tumour likely records its own
      progression within its genome. In the future, it may be possible to read the past
      based on these sequences. A critical issue is whether these autobiographies will
      recapitulate morphology or whether they reveal unexpected ghosts.

PMID- 11327119
TI  - Clustering of metabolic abnormalities in obese individuals: the role of genetic
      factors.
AB  - The objective of this paper is to review the current evidence in support of
      genetic factors underlying the clustering of components of the metabolic syndrome
      in obese individuals. It has become clear that individual features of the
      metabolic syndrome are partially determined by familial factors some of which are
      unique to a given component and others that are shared among several features. A
      few candidate genes, encoding proteins of glucose, insulin and lipid metabolism,
      lipolytic cascade, fatty acid intestinal absorption, glucocorticoid metabolism,
      haemostasis and blood pressure, have been associated with a clustering of
      metabolic abnormalities, although the functional significance of these
      associations remains to be established. Furthermore, genetic polymorphisms, such
      as those detected at several lipoprotein metabolism loci, can modulate the
      relationships between different components of the metabolic syndrome. An
      overfeeding study conducted on identical twins has demonstrated that genetic
      factors play an important role in the responsiveness to changing energy balance
      conditions. Leptin receptor, beta2 adrenergic receptor and glucocorticoid
      receptor gene polymorphisms have been associated with an augmented clustering of
      metabolic abnormalities in response to overfeeding. Gene-gene interaction effects
      between markers of the alpha2A, beta2 and beta3 adrenergic receptor genes on
      components of the metabolic syndrome have been described. Genetic factors also
      seem to modify the responsiveness of metabolic syndrome features to endurance
      training. A growing understanding of the genetic architecture of the metabolic
      syndrome may help in the prevention of this condition. The reduction of excess
      body fat, the most common clinical feature among the cluster of metabolic
      abnormalities, should be the focus of the prevention and treatment of the
      metabolic syndrome.

PMID- 11327120
TI  - Detection of Helicobacter pylori infection: when to perform which test?
AB  - This paper reviews current diagnostic techniques for Helicobacter pylori
      infection and critically questions their value under different diagnostic
      circumstances. As long as we do not have general treatment recommendations for H.
      pylori infection, endoscopy is still the basis for primary diagnosis because it
      assesses therapy indications. In addition, histology characterizes the
      gastroduodenal lesions observed and may reveal malignant diseases. New rapid
      urease tests from the biopsies are inexpensive, simple, and quick giving results
      reliably within 1 h. Culturing H. pylori from gastric samples after therapy
      failure and testing the strains for antimicrobial susceptibility is becoming
      increasingly important with higher prevalence of drug resistances. Nonendoscopic
      tests are more convenient to the patient. Serological tests inexpensively detect
      circulating IgG or IgA antibodies. However, inspite of the cost attractiveness,
      serology might be problematic in indicating present H. pylori infection. The
      tests of choice for noninvasive monitoring therapy success or failure are the 13C
      urea breath test and the faecal antigen immunoassay. Both tests are also of value
      for first diagnosis in children when endoscopy is not indicated. In the future,
      serological detection of virulence factors and polymerase chain reaction with
      molecular fingerprinting might help to identify H. pylori strains with high
      pathogenicity or antibiotic resistance.

PMID- 11327121
TI  - Cerebral blood flow and metabolism in silent brain infarction and related
      cerebrovascular disorders.
AB  - The appropriate management of silent stroke requires better understanding of the
      haemodynamic status in the brain. However, only a few studies have examined
      cerebral blood flow and metabolism in subjects with silent stroke. Positron
      emission tomography demonstrated a slight decrease in cortical blood flow with an
      increase in oxygen extraction fraction (ie misery perfusion) in subjects with
      silent brain infarction, whereas both cerebral blood flow and oxygen metabolism
      decreased in patients with symptomatic brain infarction (matched hypoperfusion).
      These findings confirm that brain circulation is haemodynamically compromised in
      subjects with silent stroke. Another important point is that subcortical silent
      stroke may induce a reduction in cortical blood flow and metabolism by a
      disconnection mechanism (ie diaschisis) between the cortex and the subcortical
      structures. Silent infarction is not innocuous in terms of compromised cerebral
      circulation, which may lead to cognitive decline or subsequent clinical stroke.
      In the future, further developments in functional imaging will permit a more
      sophisticated analysis of brain circulation and metabolism in silent stroke.

PMID- 11327122
TI  - Effectiveness of laparoscopic gonadectomy using abdominal wall lift method on
      Turner's syndrome patients with 45, X/46, XY mosaicism.
AB  - We present a Turner's syndrome patient with a 45, X/46, XY mosaicism who
      underwent a prophylactic laparoscopic gonadectomy using the abdominal wall lift
      method. The patient was a 14-year-old phenotypic girl who was referred for an
      examination of primary amenorrhea. She had already been found to have Turner's
      syndrome with 45, X/46, XY mosaicism. After an extensive discussion with the
      patient and her family regarding her high risk for developing a gonadoblastoma, a
      laparoscopic bilateral salpingo-oophorectomy using the abdominal wall-life method
      was performed. Laparoscopy using the abdominal wall lift method has an advantage
      over CO2 pneumoperitoneum method for patients with Turner's syndrome when it is
      difficult to intubate because of a webbed neck or a shortened trachea.

PMID- 11327123
TI  - Laparoscopic cryoablation of a metastatic carcinoid tumor.
AB  - Carcinoid tumors are rare, slow-growing neuroendocrine neoplasms that can cause a
      carcinoid syndrome. The majority of carcinoid syndromes are the result of
      multiple hepatic metastases and are usually unresectable. Medical therapy has not
      proven effective and often causes intolerable side effects. Cryoablation has
      emerged as a promising treatment for various hepatic lesions when resection is
      not an option and medical therapy has been exhausted. With the addition of
      laparoscopy, surgeons now possess a new technique to treat primary and various
      secondary liver lesions. We report for the first time laparoscopic cryoablation
      for the treatment of a carcinoid metastatic to the liver.

PMID- 11327124
TI  - Mechanical partial small bowel obstruction in a patient with Fitz-Hugh-Curtis
      syndrome.
AB  - Perihepatitis or Fitz-Hugh-Curtis syndrome is a complication of pelvic
      inflammatory disease that usually leaves characteristic violin string adhesions
      on the anterior liver surface. These adhesions are common incidental findings on
      subsequent laparoscopy or laparotomy and are considered benign. We present a case
      of partial mechanical small bowel obstruction as a sequel of this syndrome that
      was diagnosed and treated laparoscopically.

PMID- 11327125
TI  - Infrarenal aortic aneurysm repair by retroperitoneal approach combined with
      laparoscopic cholecystectomy: two case reports.
AB  - Simultaneous repair of abdominal aortic aneurysm and treatment of cholelithiasis
      by the transperitoneal approach is controversial because of the risk of
      prosthesis infection. We report two patients who underwent a successful combined
      procedure using a retroperitoneal approach for the aortic aneurysm repair and a
      laparoscopic approach to the cholecystectomy. This combined approach reduces the
      risk of infection of the aortic prosthesis and is associated with a rapid return
      of normal peristalsis.

PMID- 11327126
TI  - Literature watch.

PMID- 11327127
TI  - Video-assisted thoracoscopic T2 sympathetic block by clipping for palmar
      hyperhidrosis: analysis of 52 cases.
AB  - BACKGROUND: Endoscopic thoracic sympathectomy or sympathicotomy is a standard
      method in treating palmar hyperhidrosis, but postoperative compensatory sweating
      may be troublesome in some patients. Therefore, we designed a new technique for
      only T2 sympathetic blocking by clipping instead of interruption of the
      sympathetic trunk. PATIENTS AND METHODS: Between September 2000 and July 2001, we
      saw a total of 100 patients with palmar hyperhidrosis who underwent video
      assisted thoracoscopic sympathetic blocking of the T2 ganglion. All patients were
      placed in a semisitting position under single-lumen intubated anesthesia. We
      performed sympathetic blocking by clipping of the T2 ganglion at the level of the
      second and third rib beds using an 8-mm, 0 degree thoracoscope (Storz). RESULTS:
      We supposed that the postoperative improvement in palmar hyperhidrosis would be
      perfect. The operation could be accomplished within 30 minutes. All patients were
      discharged within 4 hours after the operation. Surgical complications were
      minimal, without surgical mortality. A few patients were willing to receive the
      reverse operation and should get improvement of compensatory sweating after
      removal of the endo clips. CONCLUSION: We believe that video-assisted
      thoracoscopic T2 sympathetic block by clipping will be a safe and effective
      method of treating patients with palmar hyperhidrosis. Compensatory sweating may
      be improved by the reverse operation: removal of the endo clip.

PMID- 11327128
TI  - Laparoscopic bile duct injuries: spectrum at a tertiary-care center.
AB  - BACKGROUND AND PURPOSE: Laparoscopic cholecystectomy (LC) is associated with a
      higher incidence of bile duct injury than is open cholecystectomy. We reviewed
      our experiences with the management of laparoscopic bile duct injuries. PATIENTS
      AND METHODS: From October 1992 through August 1998, 34 patients with bile duct
      injuries (BDI) following LC were seen. The presentation, type of injury
      (Strasberg classification), management, and outcome were analyzed in these
      patients. RESULTS: Of the 16 patients who sustained injury at our center (type A
      [N = 9], D [N = 5], and E1 [N = 2]), in 14, the injury was detected during LC,
      and two patients manifested with postoperative bile leak. All patients had an
      excellent outcome at a median follow-up of 5.5 (range 1.9-8.0) years. Of the 18
      patients who sustained injury elsewhere (type C [N = 1], D [N = 2], E [N = 14; 6
      with external biliary fistula (EBF) and 8 with benign biliary stricture (BBS)],
      and not known [1]), 9 had EBF, 1 had biliary peritonitis, and 8 had BBS at the
      time of presentation. Of these 18 patients, 4 underwent early repair of the BDI
      before referral (repair over a T-tube [N = 2] and Roux-Y hepaticojejunostomy [N =
      2]). Three of them developed restricture. One patient was referred to us within
      12 hours of injury and had a successful repair over a T-tube. Two patients with
      early repair for lateral injury had an excellent outcome. Eleven patients with
      BBS underwent repair with an excellent (N = 10) or fair (N = 1) outcome at a
      median follow-up of 5.0 (2.0-6.2) years. Three patients were lost to follow-up.
      CONCLUSION: The spectrum of injuries sustained at LC at a tertiary-care center is
      different from that in the community hospitals. Missed injuries and attempts at
      repair in inexperienced hands result in serious sequelae of stricture formation
      and long-term morbidity.

PMID- 11327129
TI  - Is helium insufflation superior to carbon dioxide insufflation in bacteremia and
      bacterial translocation with peritonitis?
AB  - PURPOSE: To evaluate the effects of CO2 or helium insufflation on bacteremia and
      bacterial translocation in rats with peritonitis. MATERIALS AND METHODS: Forty
      male Wistar-Albino rats were divided into four groups, each containing 10 rats.
      The rats in the first group were injected only with E. coli into their peritoneal
      cavities with no further manipulation. The second group, following E. coli
      injection, underwent midline laparotomy without manipulation of the viscera for 1
      hour. After the injection of E. coli in the third and fourth groups, CO2 and
      helium pneumoperitoneum, respectively, were maintained for 1 hour under 14 mm Hg
      pressure. At the end of the sixth hour, tissue samples were taken from the liver,
      spleen, lung, and mesenteric lymph nodes in order to evaluate bacterial
      translocation. During the study, blood samples were taken from each rat at 0, 1,
      2, 4, and 6 hours to demonstrate bacteremia. RESULTS: There was a significant
      increase in bacteremia in the CO2 pneumoperitoneum group compared with the
      laparotomy-only and helium groups at 1 and 2 hours. Although all the blood
      samples at the fourth hour were positive for E. coli in every rat of all groups,
      helium was associated with a lower incidence of bacteremia at the sixth hour
      compared with other groups (P < 0.05). The CO2 pneumoperitoneum caused bacterial
      translocation to all organs from which tissue samples were taken. Although there
      was an insignificant decrease in translocation to the liver, spleen, and lung
      with helium compared with CO2 insufflation, helium did not increase bacterial
      translocation to the spleen compared with laparotomy alone, as did CO2 (P <
      0.05). CONCLUSION: Helium might be an alternative to CO2 insufflation in patients
      with peritonitis if these results are confirmed by further experimental and
      clinical trials.

PMID- 11327130
TI  - Balloon blunt-tip trocar for laparoscopic cholecystectomy: improvement over the
      traditional Hasson and Veress needle methods.
AB  - BACKGROUND AND PURPOSE: Laparoscopic cholecystectomy (LC) is a routine procedure
      for most general surgeons, yet the technical aspects of gaining access to the
      peritoneal cavity continue to be quite diverse. We describe a prospective review
      of 180 LCs using three access techniques: open balloon blunt-tip trocar (BBTT),
      open Hasson (HA), and closed Veress needle (VN). We favor the BBTT because it is
      designed to avoid all sharp instrumentation and offers superior seal and
      mobility, as well as expeditious and easy abdominal access. PATIENTS AND METHODS:
      The techniques and devices were evaluated prospectively with regard to simplicity
      of access, leakage of carbon dioxide, access time, and complications. All
      patients underwent LC by one of two Board-certified surgeons. RESULTS: The mean
      time to insertion of the laparoscope for the BBTT (3.5 +/- 0.99 minutes) was
      significantly less than the insertion time for the VN technique (5.2 +/- 0.9
      minutes, P < 0.05). The insertion time for the BBTT was also less than for the
      standard HA approach (4.25 +/- 1.0 minutes; P < 0.05). There were no visceral or
      vascular injuries noted, but CO2 leakage and subcutaneous insufflation of gas
      experienced in the standard HA and VN groups resulted in lengthened operative
      times. One patient in the BBTT group experienced a postoperative port-site
      herniation, which was repaired primarily without consequence. CONCLUSION: The
      BBTT is an established, safe alternative to blind access for LC. Our technique is
      simple and rapid and avoids most of the technical difficulties encountered by
      other open access devices. We believe this method provides surgeons with an
      option that is efficient and easier to perform than most other conventional open
      access laparoscopic techniques.

PMID- 11327131
TI  - Laparoscopic biliopancreatic diversion with a duodenal switch for morbid obesity:
      a feasibility study in pigs.
AB  - BACKGROUND AND PURPOSE: Biliopancreatic diversion with a duodenal switch is an
      emerging open procedure that appears as effective as other bariatric operations.
      Our goal was to determine the safety and feasibility of performing this procedure
      using a laparoscopic approach in a porcine model. MATERIALS AND METHODS: Six 50
      kg pigs underwent surgery. Intake was restricted with a sleeve gastrectomy, and
      malabsorption was obtained by creating a Roux-en-Y. The Roux limb served as a 150
      cm alimentary channel following anastomosis to a transected proximal duodenum,
      while the other limb, or biliopancreatic channel, transported digestive juices.
      Where the two limbs joined, a 100-cm common channel was formed. RESULTS: The
      operation was completed in a mean time of 4.5 hours. Two of the six pigs had an
      intraoperative duodenoenterostomy anastomotic leak detected on methylene blue
      testing. This leakage was thought to be related to pig anatomy and is not
      expected to be a problem in humans. At necropsy, all anastomoses were patent, and
      there were no enteroenterostomy leaks or mesenteric torsions. CONCLUSION: On the
      basis of the porcine model, laparoscopic biliopancreatic diversion with a
      duodenal switch is anticipated to be feasible and safe in humans. Substantial
      weight loss combined with the benefits of laparoscopic surgery can be expected.

PMID- 11327132
TI  - A new method of laparoscopic cholecystectomy using three trocars combined with
      suture retraction of gallbladder.
AB  - BACKGROUND AND PURPOSE: Since the establishment of laparoscopic cholecystectomy
      (LC) for benign gallbladder lesions, the four-trocar method has been the standard
      procedure. However, the fourth trocar generally is used just for fundic
      retraction of the gallbladder. We have developed a three-trocar method for LC and
      performed it in 132 patients. PATIENTS AND METHODS: After the creation of the
      pneumoperitoneum, the first 10-mm trocar sheath was inserted in the subumbilicus
      for the endoscope, the second 5-mm trocar in the epigastric paramedian point for
      the working port, and the third 5-mm trocar in the subcostal area for grasping
      forceps. Monofilament nylon with a straight needle was inserted through the right
      7th intercostal space in the anterior axillary line, and the seromuscular layer
      of the gallbladder fundus was punctured and retracted toward the anterior
      abdominal wall. After that, usual cholecystectomy was performed. RESULTS: Among
      the 132 patients who underwent the three-trocar method, 10 cases (8%) needed a
      fourth trocar. No patient was converted to open cholecystectomy. There were no
      significant differences in the operating time, the length of hospital stay after
      the operation, or the use of analgesics between the three-trocar and the four
      trocar methods. No major complication was recognized. CONCLUSION: This method
      also has cosmetic advantages. Therefore, we believe this method might be
      recommended for LC.

PMID- 11327133
TI  - Minimally invasive approach to the cervical spine: a proposal.
AB  - BACKGROUND AND PURPOSE: During the last 3 years, a minimally invasive video
      assisted approach for parathyroidectomy and thyroidectomy has been developed.
      Because of the good exposure of the cervical spine during these procedures, the
      authors decided to perform an anatomic-radiologic study in order to evaluate
      which cervical vertebrae could be reached by this minimally invasive approach.
      PATIENTS AND METHODS: Three consenting patients, two undergoing minimally
      invasive parathyroidectomy and one a conventional operation for C4-C5 disc
      herniation, were selected for this study. The procedure was carried out through a
      single 1.5-cm central skin incision above the sternal notch. After opening of the
      cervical linea alba, dissection was performed under endoscopic vision, without
      using any CO2 insufflation or trocar. After exposure of the prevertebral fascia,
      an operative tube was introduced through the cervical incision in order to
      maintain the operative space without using conventional retractors. RESULTS:
      Through this operative tube, it was possible to introduce both a 5-mm (or 3-mm)
      endoscope and the surgical instruments. In our patients, we inserted a 1-mm metal
      probe to exactly localize during fluoroscopy the vertebrae reached by the
      dissection (C2-C7). CONCLUSIONS: This study shows the feasibility of an anterior
      minimally invasive approach to the cervical spine. Although the exact indications
      have to be verified, a video-assisted approach could add some advantages to the
      well-known benefits coming from the anterior approaches to the cervical spine,
      especially in terms of cosmetic results and postoperative course and recovery.

PMID- 11327134
TI  - Commentary: how to assess technology for laparoscopic surgery.

PMID- 11327135
TI  - Laparoscopic cholecystectomy: fundus-down approach.
AB  - BACKGROUND AND PURPOSE: Laparoscopic cholecystectomy (LC) is the primary
      treatment of gallstone disease. Although refinements have made it safer, bile
      duct injury remains more common than with the open approach. The major difference
      in these techniques is that open cholecystectomy approaches the gallbladder from
      the fundus downward, whereas conventional laparoscopic cholecystectomy proceeds
      in the reverse direction. A handful of fundus-down techniques appear in the
      literature. The use of special instruments or port sites is common. We present a
      technique that is safe and utilizes instruments familiar to the surgeon
      performing conventional LC. PATIENTS AND METHODS: Fifty consecutive LCs were
      included in the study. The variables monitored were age, comorbidities,
      postoperative diagnosis, pathologic diagnosis, length of operation, hospital
      length of stay, and complications. RESULTS: The average operating time for
      chronic cholecystitis was 1 hour, and the average time for acute cholecystitis
      was less than 2 hours. Except for one early case of bleeding, in which the
      procedure was completed using the familiar conventional method, no complications
      and no unusual technical difficulties were encountered. There were no differences
      between conventional and fundus-down LC with regard to time and complications.
      CONCLUSIONS: This technique is safe and has several benefits: (1) standard trocar
      sites that offer the surgeon flexibility in the approach; (2) the ability to
      resect as much cystic duct as desired; and (3) utilization of standard
      instruments familiar to the surgeon, thus avoiding costly special instruments.
      The approach may offer the benefit of reducing the rate of common bile duct
      injury to that of open cholecystectomy.

PMID- 11327136
TI  - 'I think condoms are good but, aai, I hate those things': condom use among
      adolescents and young people in a Southern African township.
AB  - Levels of heterosexually transmitted HIV infection are high amongst South African
      youth, with one recent survey reporting levels of 18.9% amongst 17-20 year olds
      and 43.1% amongst 21-25 year olds. In these groups levels of knowledge about HIV
      are high, but perceived vulnerability and reported condom use are low. Much
      existing research into youth HIV in developing countries relies on survey
      measures which use individual knowledge, attitudes and reported behaviour as
      variables in seeking to explain HIV transmission amongst this group. This paper
      reports on a focus group study that seeks to complement existing individual-level
      quantitative findings with qualitative findings highlighting community and social
      factors that hinder condom use amongst youth in the township of Khutsong, near
      Carletonville. Study informants comprised 44 young women and men in the 13-25
      year age group. Data analysis highlighted six factors hindering condom use: lack
      of perceived risk; peer norms; condom availability; adult attitudes to condoms
      and sex; gendered power relations and the economic context of adolescent
      sexuality. Informants did not constitute a homogenous group in terms of their
      understandings of sexuality. While there was clear evidence for the existence of
      dominant social norms which place young peoples' sexual health at risk, there was
      also evidence that many young people are self-consciously critical of the norms
      that govern their sexual behaviour, despite going along with them, and that they
      are aware of the way in which peer and gender pressures place their health at
      risk. There was also evidence that a minority of youth actively challenge
      dominant norms and behave in counter-normative and health-enhancing ways. The
      actively contested nature of dominant sexual norms provides a fertile starting
      point for peer education programmes that seek to provide the context for the
      collective negotiation of alternative sexual norms that do not endanger young
      peoples' sexual health.

PMID- 11327137
TI  - Trends in healthy life expectancy in the United States, 1970-1990: gender,
      racial, and educational differences.
AB  - This paper examines healthy life expectancy by gender and education for whites
      and African Americans in the United States at three dates: 1970, 1980 and 1990.
      There are large racial and educational differences in healthy life expectancy at
      each date and differences by education in healthy life expectancy are even larger
      than differences in total life expectancy. Large racial differences exist in
      healthy life expectancy at lower levels of education. Educational differences in
      healthy life expectancy have been increasing over time because of widening
      differentials in both mortality and morbidity. In the last decade, a compression
      of morbidity has begun among those of higher educational status; those of lower
      status are still experiencing expansion of morbidity.

PMID- 11327139
TI  - Perceived control in relation to socioeconomic and behavioral resources for
      health.
AB  - Perceived control is a personality characteristic that contributes to well-being,
      but few studies have attempted to integrate the functions of perceived control
      with those of other determinants of health. This research tested two hypotheses
      about the functions of perceived control: (a) individual differences in perceived
      control would account for socioeconomic differences in self-rated health status;
      (b) performance of health-related behaviors would account for the health benefits
      of perceived control. Using data from adult, nonproxy respondents in the National
      Population Health Survey of Canada (1995; n = 11, 110), confirmatory factor
      analysis supported a measurement model of self-rated health status composed of
      two correlated factors: physical health (i.e., chronic conditions. restricted
      activities, self-rated general health, physical functional capacity) and mental
      health (i.e., distress, depression). Structural equation modeling supported the
      first hypothesis, but not the second, regarding perceived control as a
      determinant of self-rated physical and mental health. Health-related behaviors
      partially mediated age differences in self-rated health, but different behaviors
      functioned in this way for men than for women. The findings suggest that
      psychological process, that of perceiving control over life events, underlies
      social inequality in health. Health-related behaviors appear not to serve as the
      primary mechanism through which perceived control influences health.

PMID- 11327138
TI  - "Being dealt with as a whole person." Care seeking and adherence: the benefits of
      culturally competent care.
AB  - The purpose of this study is to characterize the relationship between identity
      and health care experiences (including antiretroviral therapy utilization) among
      HIV-positive sexual minority males. This qualitative study used grounded theory
      with data collection occurring through focus groups and interviews. A
      questionnaire was used to complete a demographic profile. The study included 47
      HIV positive participants from three minorities: gay men, bisexual men and
      transgendered persons, gender identifying as female and or living as women.
      Sessions elicited information on: (1) general experiences with health care, (2)
      experiences with HIV antiretroviral therapies and issues surrounding access, and
      (3) adherence to these therapies and identity in relation to health care. These
      textual data revealed three themes: (1) the importance of sexual identity and its
      social and cultural context, (2) the differences in the health concerns between
      the sexual minorities and (3) a wide spectrum of experiences with the health care
      system that provide information surrounding the access to and adequacy of health
      care. Successful health care providers are aware of different issues that may
      play a role in the provision of health care to these sexual minorities. Providers
      awareness of sexual and social identity and the related different cultural
      values, beliefs and custom enhance care seeking and therapeutic adherence. For
      sexual minorities, primary care remains the most important entry point into the
      health care system. Cultural competence of care providers can foster patient's
      care seeking and adherence to treatment.

PMID- 11327140
TI  - The ethics of social risk reduction in the era of the biological brain.
AB  - In keeping with our transdisciplinary orientation, in this article we try to do
      several things at once. We address research on preventing mental illness and its
      relation to existing conceptions of public health, a topic to which insufficient
      attention has been paid in the era of the biological brain, while using this case
      study to illustrate the limits of conventional approaches in bioethics. After
      identifying the crucial need for methodological self-consciousness in prevention
      research and policy, we explore the implications as they relate to (i) the values
      embedded in the choice of research designs and strategies, and (ii) contrasting
      intellectual starting points regarding the biological plausibility of preventing
      mental illness. We then draw attention to the need for more thoughtful analysis
      of the appropriate role and limits of economics in making choices about
      prevention of mental illness.

PMID- 11327141
TI  - The closure of rural hospitals in Saskatchewan: method or madness?
AB  - On April 14, 1993 the Minister of Health of the Province of Saskatchewan
      announced the closure of 52 of the 112 small hospitals using the criteria of:
      size, utilization for two consecutive years and distance to the nearest
      neighbouring hospital. Amazingly, that government was re-elected. This study
      compared two models of reasons for hospital closure: the government criteria; and
      historical population, resource, and utilization factors, gathered for the year
      prior to closure and a decade earlier. Of the 112 small hospitals in
      Saskatchewan, the 10 hospitals in the frontier area were not included. Hospitals
      in the settled part of the province were divided into two distinct zones. The
      Northern zone, with 53 hospitals is characterized by rich dark soil and
      prosperous trade centres and the Southern zone, with 49 hospitals is
      characterized by light brown sandy soil and oil and gas exploration centres. Two
      discriminant models were developed. The government model consisted of size, two
      years of utilization and distance. The historical model consisted of population,
      resource, and utilization factors for the years 1981/1982 and 1991/1992. The
      dependent variable for both models was hospital status (open = 1 and closed = 0).
      The government model accurately predicted 91.18% of the closure decisions. The
      historical model had a classification accuracy of 95.10% for the whole of settled
      Saskatchewan, 96.23% for the Northern zone, and 95.92% for the Southern zone. The
      historical model was more accurate than the government model. Closing a hospital
      is a sad event. The manner in which the government closed nearly half of the
      small hospitals in Saskatchewan and gained re-election is an important account of
      responsible public policy. The historical model developed to examine this story
      takes public policy one step further in that it is possible for governments to
      recognize signals that indicate when communities should undertake orderly
      transitions in the operation of their health services facilities.

PMID- 11327142
TI  - Emerging paradigms in the mental health care of refugees.
AB  - Over the past decade the approaches adopted towards the mental health care of
      refugees by a range of national and international healthcare organisations have
      been the subject of a sustained and growing critique. Much of this critique has
      focused on the way in which Western psychiatric categories have been ascribed to
      refugee populations in ways which, critics argue, pay scant attention to the
      social, political and economic factors that play a pivotal role in refugees'
      experience. Rather than portraying refugees as "passive victims" suffering mental
      health problems, critics have argued that attention should be given to the
      resistance of refugees and the ways in which they interpret and respond to
      experiences, challenging the external forces bearing upon them. In this paper a
      range of issues concerning the mental health care of refugees will be examined.
      These include the role of psychiatric diagnosis in relation to refugees' own
      perceptions of their need and within the context of general health and social
      care provision. In examining services the emergence of new paradigms in mental
      health care is identified. These include the growth of holistic approaches that
      take account of refugees' own experiences and expressed needs and which address
      the broader social policy contexts in which refugees are placed. A three
      dimensional model for the analysis of the interrelationship between "macro" level
      institutional factors in the mental health of refugees and the individual
      treatment of refugees within mental health services is proposed.

PMID- 11327143
TI  - On reflection: doctors learning to care for people who are dying.
AB  - Humane care is an essential component of the doctor's role at the end of life.
      Over the last 20 years, there has been a steady global increase in the extent and
      variety of medical teaching about the care of people who are dying. In some
      countries, palliative medicine is now recognised as a discrete medical specialty.
      Rightly, much emphasis has been placed on symptom management, communication
      skills and ethical issues. But rarely does the concept of care, or how doctors
      learn to care, emerge in the medical literature. The concept of "care" is usually
      defined as a professional behaviour: attending to a patient's needs. Yet, the
      concept of care also requires a professional commitment on a more holistic level.
      To care is to be receptive to and responsible for others. This is care motivated
      by true empathy: a concern for the patient's well-being that comes from a
      sensitive identification with the patient's situation. This paper reports some of
      the findings from an interpretive phenomenological study involving 10 doctors and
      their experiences of learning to care for people who were dying. The doctors came
      from differing medical disciplines and had varying levels of experience. During
      the interviews the doctors retrospectively identified "turning points" at which
      they first perceived some notion of what it means to care for someone who is
      dying. The doctors often used poignant language when recollecting the strong
      feelings associated with these critical incidents. They felt that their training
      had been inadequate in preparing them for such care. The article asks whether
      their medical education had adequately prepared these doctors for this key
      element of their work. It recommends ways in which practitioners may be better
      prepared to care for people who are dying.

PMID- 11327144
TI  - Recurrent symptoms: well-being and management.
AB  - Although most older adults report one or more symptoms of a chronic health
      problem, little attention has been paid to the report of these symptoms over time
      and whether different symptom patterns affect well-being and symptom management
      in community-dwelling elders. Therefore, this study examined whether community
      dwelling older adults in Ohio, U.S.A. who experience consistently recurring (a)
      arthritis or (b) cardiopulmonary symptoms report more depression and worse self
      assessed health and show more symptom management than those who report
      inconsistent symptoms and if there are differences in well-being and symptom
      management over time. This secondary analysis used longitudinal data collected
      from a random sample of 387 older adults who reported their health complaints in
      four interviews over 27 months time. Subjects were included in this analysis if
      they reported either arthritis (n = 321) or cardiopulmonary (n = 232) symptoms at
      one or more times during 27 months, and then were classified as having either
      consistent (occurring at all four time points) or intermittent/inconsistent
      (occurring at three or fewer time points) symptoms. Data analysis included t
      tests, chi-square tests, and Repeated Measures ANOVA. Results indicate that those
      with consistent symptoms reported greater depression and worse self-assessed
      health than those with less consistent symptoms. Specifically, those with
      consistent cardiopulmonary symptoms became more depressed over time. Those with
      consistent cardiopulmonary complaints were more likely than those with an
      inconsistent pattern to use an illness label to describe their symptoms. Those
      with consistent arthritis symptoms tended to use more self-care at all time
      points, to label their symptoms as an illness, and were more likely to consult a
      physician as their symptoms persisted. The implications of symptom recurrence on
      well-being, symptom management and the concept chronicity are discussed.

PMID- 11327145
TI  - Transitions of employment status among suicide attempters during a severe
      economic recession.
AB  - Previous studies have shown a positive association between unemployment and
      attempted suicide. This study investigated transitions of employment status among
      suicide attempters during the severe economic recession. The main research
      question was whether inequality in the labour market also prevails among as
      selected a population as suicide attempters. The material consisted of 2495
      persons who attempted suicide during 1989-1994 in Helsinki, Finland. Logistic
      regression analysis and survival analysis were used. Unemployment rates among
      suicide attempters were higher than in the general population, male rates being
      higher than female rates throughout the recession. There were significant changes
      in the employment status of the entire attempted suicide population from 1989 to
      1994, especially in terms of the transition from employment to unemployment.
      Gender, age and education level predicted exit from the labour market. Among
      suicide attempters young middle-aged men with low education had the highest risk
      of unemployment.

PMID- 11327146
TI  - GIS approaches to the problem of disease clusters: a brief commentary.
AB  - This commentary considers issues raised in a recent article on GIS-based
      approaches to modeling disease clusters. 'Modeling exposure opportunities'
      (Sabel, Gatrell & Loytonen et al., 2000. Social Science and Medicine, 50, 1121
      37) and the general problem of mapping disease clusters. It notes that the
      authors' advocate a fundamentally statistical approach, Kerneling estimation, to
      map the occurrence of a specific illness whose etiology is unknown.
      Epidemiologists, ironically, have advocated a fundamentally cartographic
      solution, the cartogram, in addressing the general problem of disease clusters.
      The advantages and limits of both approaches are reviewed and the potential for
      their comparison in a single study suggested. Most importantly, perhaps, the
      commentary seeks to join the epidemiological and medical geographic literatures
      as they pertain to this analytic problem and medical cartography's potential (GIS
      based or traditional) to understand disease etiology.

PMID- 11327147
TI  - Selective targeting of glutamate receptors in neurons.
AB  - Glutamate receptors mediate the majority of excitatory responses in the central
      nervous system (CNS). Neurons express multiple subtypes and subunits of glutamate
      receptors, which are differentially distributed at pre- and postsynaptic sites.
      This allows the cell to respond differentially depending on the subunit
      composition of receptors at the postsynaptic membrane. The process by which
      receptors are targeted selectively to the appropriate synapse is poorly
      understood. Evidence exists that targeting of glutamate receptors to the
      different neuronal compartments is regulated at multiple levels involving a
      general targeting step; a local step where receptor-containing organelles are
      moved to the synapse; and a step where the receptors are stabilized at the
      synapse, which may involve interaction with an anchoring protein.

PMID- 11327148
TI  - Opioid tolerance and the emergence of new opioid receptor-coupled signaling.
AB  - Multiple cellular adaptations are elicited by chronic exposure to opioids. These
      include diminution of spare opioid receptors, decreased opioid receptor density,
      and G-protein content and coupling thereof. All imply that opioid tolefance is a
      manifestation of a loss of opioid function, i.e., desensitization. Recent
      observations challenge the exclusiveness of this formulation and indicate that
      opioid tolerance also results from qualitative changes in opioid signaling. In
      this article, Gintzler and Chakrabarti discuss the evidence that suggests that
      opioid tolerance results not only from impaired opioid receptor functionality,
      but also from altered consequences of coupling. Underlying the latter are
      fundamental changes in the nature of effectors that are coupled to the opioid
      receptor/G-protein signaling pathway. These molecular changes include the
      upregulation of adenylyl cyclase isoforms of the type II family as well as a
      substantial increase in their phosphorylation state. As a result, there is a
      shift in opioid receptor/G-protein signaling from predominantly Gialpha
      inhibitory to Gbetagamma stimulatory following chronic in vivo morphine exposure.
      These adaptations to chronic morphine indicate the plasticity of opioid-signal
      transduction mechanisms and the ability of chronic morphine to augment new
      signaling strategies.

PMID- 11327149
TI  - A statistical view of FMRFamide neuropeptide diversity.
AB  - FMRFamide-like peptide (FLP) amino acid sequences have been collected and
      statistically analyzed. FLP amino acid composition as a function of position in
      the peptide is graphically presented for several major phyla. Results of total
      amino acid composition and frequencies of pairs of FLP amino acids have been
      computed and compared with corresponding values from the entire GenBank protein
      sequence database. The data for pairwise distributions of amino acids should help
      in future structure-function studies of FLPs. To aid in future peptide discovery,
      a computer program and search protocol was developed to identify FLPs from the
      GenBank protein database without the use of keywords.

PMID- 11327150
TI  - A neural systems analysis of adaptive navigation.
AB  - In the field of the neurobiology of learning, significant emphasis has been
      placed on understanding neural plasticity within a single structure (or synapse
      type) as it relates to a particular type of learning mediated by a particular
      brain area. To appreciate fully the breadth of the plasticity responsible for
      complex learning phenomena, it is imperative that we also examine the neural
      mechanisms of the behavioral instantiation of learned information, how
      motivational systems interact, and how past memories affect the learning process.
      To address this issue, we describe a model of complex learning (rodent adaptive
      navigation) that could be used to study dynamically interactive neural systems.
      Adaptive navigation depends on the efficient integration of external and internal
      sensory information with motivational systems to arrive at the most effective
      cognitive and/or behavioral strategies. We present evidence consistent with the
      view that during navigation: 1) the limbic thalamus and limbic cortex is
      primarily responsible for the integration of current and expected sensory
      information, 2) the hippocampal-septal-hypothalamic system provides a mechanism
      whereby motivational perspectives bias sensory processing, and 3) the amygdala
      prefrontal-striatal circuit allows animals to evaluate the expected reinforcement
      consequences of context-dependent behavioral responses. Although much remains to
      be determined regarding the nature of the interactions among neural systems, new
      insights have emerged regarding the mechanisms that underlie flexible and
      adaptive behavioral responses.

PMID- 11327151
TI  - The cerebral proteopathies: neurodegenerative disorders of protein conformation
      and assembly.
AB  - The abnormal assembly and deposition of specific proteins in the brain is the
      probable cause of most neurodegenerative disease afflicting the elderly. These
      "cerebral proteopathies" include Alzheimer's disease (AD), Parkinson's disease
      (PD), Huntington's disease (HD), prion diseases, and a variety of other
      disorders. Evidence is accumulating that the anomalous aggregation of the
      proteins, and not a loss of protein function, is central to the pathogenesis of
      these diseases. Thus, therapeutic strategies that reduce the production,
      accumulation, or polymerization of pathogenic proteins might be applicable to a
      wide range of some of the most devastating diseases of old age.

PMID- 11327153
TI  - Maternal effect genes and the evolution of sociality in haplo-diploid organisms.
AB  - Maternal care and female-biased sex ratios are considered by many to be essential
      prerequisites for the evolution of eusocial behaviors among the hymenoptera.
      Using population genetic models, I investigate the evolution of genes that have
      positive maternal effects but negative, direct effects on offspring fitness. I
      find that, under many conditions, such genes evolve more easily in haplo-diploids
      than in diplo-diploids. In fact, the conditions are less restrictive than those
      of kin selection theory, which postulate genes with negative direct effects but
      positive sib-social effects. For example, the conditions permitting the evolution
      of maternal effect genes are not affected if females mate multiply, whereas
      multiple mating reduces the efficacy of kin selection by reducing genetic
      relatedness within colonies. Inbreeding also differentially facilitates evolution
      of maternal effect genes in haplo-diploids relative to diplo-diploids, although
      it does not differentially affect the evolution of sib-altruism genes.
      Furthermore, when the direct, deleterious pleiotropic effect is restricted to
      sons, a maternal effect gene can evolve when the beneficial maternal effect is
      less than half (with inbreeding, much less) of the deleterious effect on sons.
      For kin selection, however, the sib-social benefits must always exceed the direct
      costs because genetic relatedness is always less than or equal to 1.0. The
      results suggest that haplo-diploidy facilitates (1) the evolution of maternal
      care, and (2) the evolution of maternal effect genes with antagonistic
      pleiotropic effects on sons. The latter effect may help explain the tendency
      toward female-biased sex ratios in haplo-diploids, especially those with
      inbreeding. I conclude that haplo-diploidy not only facilitates the evolution of
      sister-sister altruism by kin selection but also facilitates the evolution of
      maternal care and female-biased sex ratios, two prerequisites for eusociality.

PMID- 11327152
TI  - Signal-regulated ADF/cofilin activity and growth cone motility.
AB  - It is becoming increasingly evident that proteins of the actin depolymerizing
      factor (ADF)/cofilin family are essential regulators of actin turnover required
      for many actin-based cellular processes, including motility. ADF can increase
      actin turnover by either increasing the rate of actin filament treadmilling or by
      severing actin filaments. In neurons ADF is highly expressed in neuronal growth
      cones and its activity is regulated by many signals that affect growth cone
      motility. In addition, increased activity of ADF causes an increase in neurite
      extension. ADF activity is inhibited upon phosphorylation by LIM kinases (LIMK),
      kinases activated by members of the Rho family of small GTPases. ADF become
      dephosphorylated downstream of signal pathways that activate PI-3 kinase or
      increase levels of intracellular calcium. The growth-regulating effects of ADF
      together with its ability to be regulated by a wide variety of guidance cues,
      suggest that ADF may regulate growth cone advance and navigation.

PMID- 11327154
TI  - Population mixing and the adaptive divergence of quantitative traits in discrete
      populations: a theoretical framework for empirical tests.
AB  - Empirical tests for the importance of population mixing in constraining adaptive
      divergence have not been well grounded in theory for quantitative traits in
      spatially discrete populations. We develop quantitative-genetic models to examine
      the equilibrium difference between two populations that are experiencing
      different selective regimes and exchanging individuals. These models demonstrate
      that adaptive divergence is negatively correlated with the rate of population
      mixing (m, most strongly so when m is low), positively correlated with the
      difference in phenotypic optima between populations, and positively correlated
      with the amount of additive genetic variance (G, most strongly so when G is low).
      The approach to equilibrium is quite rapid (fewer than 50 generations for two
      populations to evolve 90% of the distance to equilibrium) when either
      heritability or mixing are not too low (h2 > 0.2 or m > 0.05). The theory can be
      used to aid empirical tests that: (1) compare observed divergence to that
      predicted using estimates of population mixing, additive genetic
      variance/covariance, and selection; (2) test for a negative correlation between
      population mixing and adaptive divergence across multiple independent population
      pairs; and (3) experimentally manipulate the rate of mixing. Application of the
      first two of these approaches to data from two well-studied natural systems
      suggests that population mixing has constrained adaptive divergence for color
      patterns in Lake Erie water snakes (Nerodia sipedon), but not for trophic traits
      in sympatric pairs of benthic and limnetic stickleback (Gasterosteus aculeatus).
      The theoretical framework we outline should provide an improved basis for future
      empirical tests of the role of population mixing in adaptive divergence.

PMID- 11327155
TI  - Sink-limitation and the size-number trade-off of organs: production of organs
      using a fixed amount of reserves.
AB  - To analyze the nature of size-number trade-off of organs, we develop models in
      which the effects of sink-limitation in the growth of organs and the loss of
      resources by maintenance respiration are taken into consideration. In these
      models, the resource absorption rate of an organ is proportional to either its
      absolute size or its surface area and either the initial size of an organ or the
      total initial size of the organs produced is fixed. In all models, organs are
      produced using a fixed amount of reserved resources and no additional resources
      become newly available for their growth. We theoretically show that size-number
      trade-offs are nonlinear if the resource absorption rate of an organ is
      proportional to the absolute size of the organ and the initial size of the
      individual organs is fixed or if the resource absorption rate of an organ is
      proportional to the surface area of the organ. In these nonlinear size-number
      trade-offs, the size of individual organs increases less rapidly than in linear
      trade-offs with a decrease in the number of organs and the total size of organs
      is an increasing function of the number of organs produced. This implies that
      increasing the number of organs produced is advantageous in terms of resource-use
      efficiency. In contrast, size-number trade-off is linear if the resource
      absorption rate of an organ is proportional to the absolute size of the organ and
      there is a linear trade-off between the initial size of organs and their number.
      To exemplify the effects of those size-number trade-offs on the life-history
      evolution, we calculate the optimal offspring sizes that maximize the number of
      offspring successfully being established. In the case of nonlinear size-number
      trade-offs, the optimal offspring sizes are smaller than the optimal offspring
      size in the case of linear size-number trade-offs, namely, that in the model of
      Smith and Fretwell (1974). Our optimal offspring size depends on the metabolism
      of organ development; the optimal offspring size decreases with an increase in
      maintenance respiration rate relative to the growth coefficient of organs.

PMID- 11327156
TI  - Vestigial organs as opportunities for functional innovation: the example of the
      Penstemon staminode.
AB  - Vestigial organs arise commonly during morphological evolution, but they need not
      be destined for elimination. Instead, vestigial organs may facilitate functional
      innovation because their freedom from functional constraints allows them to
      assume novel roles that their functional progenitor could not perform. We
      illustrate this vestigial transition between functions with an experimental study
      of the staminode of Penstemon flowers. Previous phylogenetic and developmental
      studies indicate that this staminode represents a stamen that was lost
      phenotypically, but not genetically, and then reappeared in the tribe Cheloneae,
      to which Penstemon belongs. To assess whether the Penstemon staminode has adopted
      a novel function(s), we compared pollination of flowers with and without
      staminodes for two bee-pollinated species, P. ellipticus and P. palmeri, and two
      hummingbird-pollinated species, P. centranthifolius and P. rostriflorus. The
      staminode acts differently in the two bee-pollinated species. For P. ellipticus,
      which represents the basal Penstemon lineage, the staminode hinders pollinator
      access to nectar, which increases visit duration and pollinator contact with
      sexual organs, thereby increasing pollen receipt by stigmas and controlling
      pollen removal from anthers. In contrast, in P. palmeri, the staminode acts as a
      lever that enhances stigma contact with the pollinator, so that staminode removal
      reduced pollen receipt, but did not affect pollinator attraction, visit duration,
      or pollen removal. Unlike in bee-pollinated species. staminode removal from
      hummingbird-pollinated species did not affect any measured aspect of pollination,
      indicating that the staminode serves no function in this derived pollination
      system. These results illustrate several features of vestigial organs: loss of
      function can be temporary; loss of function facilitates the evolution of novel
      roles; and functional reinvention will often involve only a single role, thus
      increasing the chance of both secondary loss of function (bird-pollinated
      penstemons) and functional switches (P. palmeri).

PMID- 11327157
TI  - Nuclear and cytoplasmic contributions to intraspecific divergence in an annual
      legume.
AB  - The genetic architecture of trait differentiation was evaluated between two
      ecologically distinct populations of Chamaecrista fasciculata. Individuals from
      Maryland and Illinois populations were crossed to create 10 types of seed:
      Maryland and Illinois parents, reciprocal F1 and F2 hybrids, and backcrosses to
      Maryland and to Illinois on reciprocal F1 hybrids. Reciprocal crosses created
      hybrid generation seeds with both Maryland and Illinois cytoplasmic backgrounds.
      Experimental individuals were grown in a common garden near the site of the
      Maryland population. In the garden, plants from the Illinois population flowered,
      set fruit, and died earlier than those from Maryland, likely reflecting
      adaptations to differences in growing season length between the two populations.
      Although reproductive components at the flower and whole plant level differed
      between the two populations, reproductive output as measured by fruit and seed
      production was similar. Cytoplasmic genes had a subtle but pervasive effect on
      population differentiation; hybrids with Maryland cytoplasm were significantly
      differentiated from those with Illinois cytoplasm when all characters were
      evaluated jointly. The nuclear genetic architecture of population differentiation
      was evaluated with joint scaling tests. Depending on the trait, both additive and
      nonadditive genetic effects contributed to population differentiation.
      Intraspecific genetic differentiation in this wild plant species appears to
      reflect a complex genetic architecture that includes the contribution of
      additive, dominance, and epistatic components in addition to subtle cytoplasmic
      effects.

PMID- 11327158
TI  - The quantitative genetics of fluctuating asymmetry.
AB  - Fluctuating asymmetry (subtle departures from identical expression of a trait
      across an axis of symmetry) in many taxa is under stabilizing selection for
      reduced asymmetry. However, lack of reliable estimates of genetic parameters for
      asymmetry variation hampers our ability to predict the evolutionary outcome of
      this selection. Here we report on a study, based on analysis of variation within
      and between isofemale lines and of generation means (line-cross analysis),
      designed to dissect in detail the quantitative genetics of positional fluctuating
      asymmetry (PFA) in bristle number in natural populations of Drosophila falleni.
      PFA is defined as the difference between the two sides of the body in the
      placement or position of components of a meristic trait. Heritability (measured
      at 25 degrees C) of two related measures of PFA were 13% and 21%, both of which
      differed significantly from zero. In contrast, heritability estimates for
      fluctuating asymmetry in the total number of anterior (0.7%) and transverse
      (2.4%) sternopleural bristles were smaller, not significant, and in quantitative
      agreement with previously published estimates. Heritabilities for bristle number
      (trait size) were considerably greater than that for any asymmetry measure. The
      experimental design controlled for the potentially confounding effects of common
      familial environment, and repeated testing revealed that PFA differences between
      lines were genetically stable for up to 16 generations in the laboratory at 25
      degrees C. We performed line cross analysis between strains at the extremes of
      the PFA distribution (highest and lowest values); parental strains, F1, F1r
      (reciprocal), F2, backcross, and backcross reciprocal generations were
      represented. The inheritance of PFA was described best by additive and dominance
      effects localized to the X-chromosomes, whereas autosomal dominance effects were
      also detected. Epistatic, maternal, and cytoplasmic effects were not detected.
      The inheritance of trait size was notably more complex and involved significant
      autosomal additive, dominance, and epistatic effects; maternal dominance effects;
      and additive and dominance effects localized to the X-chromosomes. The additive
      genetic correlation between PFA and its associated measure of trait size was
      negative (-0.049), but not statistically significant, indicating that the loci
      contributing additive genetic effects to these traits are probably different. It
      is suggested that PFA may be a sensitive measure of developmental instability
      because PFA taps the ability of an organism to integrate interconnected
      developmental pathways.

PMID- 11327159
TI  - The genetics of reproductive isolation and the potential for gene exchange
      between Drosophila pseudoobscura and D. persimilis via backcross hybrid males.
AB  - Hybrid male sterility, hybrid inviability, sexual isolation, and a hybrid male
      courtship dysfunction reproductively isolate Drosophila pseudoobscura and D.
      persimilis. Previous studies of the genetic bases of these isolating mechanisms
      have yielded only limited information about how much and what areas of the genome
      are susceptible to interspecies introgression. We have examined the genetic basis
      of these barriers to gene exchange in several thousand backcross hybrid male
      progeny of these species using 14 codominant molecular genetic markers spanning
      the five chromosomes of these species, focusing particularly on the autosomes.
      Hybrid male sterility, hybrid inviability, and the hybrid male courtship
      dysfunction were all associated with X-autosome interactions involving primarily
      the inverted regions on the left arm of the X-chromosome and the center of the
      second chromosome. Sexual isolation from D. pseudoobscura females was primarily
      associated with the left arm of the X-chromosome, although both the right arm and
      the center of the second chromosome also contributed to it. Sexual isolation from
      D. persimilis females was primarily associated with the second chromosome. The
      absence of isolating mechanisms being associated with many autosomal regions,
      including some large inverted regions that separate the strains, suggests that
      these phenotypes may not be caused by genes spread throughout the genome. We
      suggest that gene flow between these species via hybrid males may be possible at
      loci spread across much of the autosomes.

PMID- 11327160
TI  - The phylogenetics and biochemistry of host-plant specialization in Melitaeine
      butterflies (Lepidoptera: Nymphalidae).
AB  - Butterflies in the tribe Melitaeini (Lepidoptera: Nymphalidae) are known to
      utilize host plants belonging to 16 families, although most host-plant records
      are from four families. Of the 16 host-plant families, 12 produce secondary plant
      metabolites called iridoids. Earlier studies have shown that larvae of several
      melitaeine species use iridoids as feeding stimulants and sequester these
      compounds for larval defense. I investigate the evolutionary history of host
      plant use in the tribe Melitaeini by testing a recent phylogenetic hypothesis of
      65 species representing the four major species groups of the tribe. By simple
      character optimization of host-plant families and presence/absence of iridoids in
      the host plants, I find that plant chemistry is a more conservative trait than
      plant taxonomy. The ancestral host plant(s) of the entire tribe most likely
      contained iridoids and were likely to be in the plant family Plantaginaceae. A
      major host shift from plants containing iridoids to plants not containing
      iridoids has happened three times independently. The results show that the
      evolution of host-plant use in melitaeines has been (and still is) a dynamic
      process when considering plant taxonomy, but is relatively stable when
      considering host-plant chemistry.

PMID- 11327161
TI  - The endocrine-genetic basis of life-history variation: the relationship between
      the ecdysteroid titer and morph-specific reproduction in the wing-polymorphic
      cricket Gryllus firmus.
AB  - The hormonal basis of variation in life-history traits is a poorly studied topic
      in life-history evolution. An important step in identifying the endocrine-genetic
      causes of life-history variation is documenting statistical and functional
      associations between hormone titers and genotypes/phenotypes that vary in life
      history traits. To this end, we compared the blood ecdysteroid titer and the mass
      of the ovaries during the first week of adulthood among a flight-capable morph
      and two flightless morphs of the wing-polymorphic cricket Gryllus firmus.
      Ecdysteroids are a group of structurally related hormones that regulate many
      important aspects of reproduction in insects. Both the ecdysteroid titer and
      ovarian mass were significantly higher in each of two flightless morphs compared
      with the flight-capable morph throughout the first week of adulthood. Genetically
      based differences in the ecdysteroid titer and ovarian mass between morphs from
      different selected lines were similar to phenotypically based differences among
      morphs from the same control (unselected) lines. By day 7 of adulthood, ovaries
      were typically 200-400% larger and the ecdysteroid titer was 60-300% higher in
      flightless versus the flight-capable morph. In addition, highly significant,
      positive, phenotypic correlations were observed between the ecdysteroid titer and
      ovarian mass in pooled samples of the two flightless and flight-capable crickets
      from control lines or from selected lines. The ecdysteroid titer was sufficiently
      elevated in the flightless morphs to account for their elevated ovarian growth.
      This is the first direct documentation that naturally occurring
      phenotypes/genotypes that differ in early fecundity, a key life-history trait,
      also differ phenotypically and genetically in the titer of a key reproductive
      hormone that potentially regulates that trait.

PMID- 11327162
TI  - The evolution of armament strength: evidence for a constraint on the biting
      performance of claws of durophagous decapods.
AB  - Performance data for the claws of six sympatric species of Cancer crabs confirmed
      a puzzling pattern reported previously for two other decapod crustaceans (stone
      crabs, Menippe mercenaria, and lobsters, Homarus americanus): Although biting
      forces increased, maximum muscle stresses (force per unit area) declined with
      increasing claw size. The negative allometry of muscle stress and the stress at a
      given claw size were fairly consistent within and among Cancer species despite
      significant differences in adult body size and relative claw size, but were not
      consistent among decapod genera. Therefore, claw height can be used as a reliable
      predictor of maximum biting force for the genus Cancer, but must be used with
      caution as a predictor of maximum biting force in wider evolutionary and
      biogeographical comparisons of decapods. The decline in maximum muscle stress
      with increasing claw size in Cancer crabs contrasts with the pattern in several
      other claw traits. Significantly, three traits that affect maximal biting force
      increased intraspecifically with increasing claw size: relative claw size,
      mechanical advantage, and sarcomere length of the closer muscle. Closer apodeme
      area and angle of pinnation of the closer muscle fibers varied isometrically with
      claw size. The concordant behavior of these traits suggests selection for higher
      biting forces in larger crabs. The contrast between the size dependence of muscle
      stress (negative allometry) and the remaining claw traits (isometry or positive
      allometry) strongly suggests that an as yet unidentified constraint impairs
      muscle performance in larger claws. The negative allometry of muscle stress in
      two distantly related taxa (stone crabs and lobsters) further suggests this
      constraint may be widespread in decapod crustaceans. The implications of this
      performance constraint for the evolution of claw size and the "arms-race" between
      decapod predators and their hard-shelled prey is discussed.

PMID- 11327163
TI  - Phylogeography of Ophioblennius: the role of ocean currents and geography in reef
      fish evolution.
AB  - Many tropical reef fishes are divided into Atlantic and East Pacific taxa,
      placing similar species in two very different biogeographic regimes. The tropical
      Atlantic is a closed ocean basin with relatively stable currents, whereas the
      East Pacific is an open basin with unstable oceanic circulation. To assess how
      evolutionary processes are influenced by these differences in oceanography and
      geography, we analyze a 630-bp region of mitochondrial cytochrome b from 171
      individuals in the blenniid genus Ophioblennius. Our results demonstrate deep
      genetic structuring in the Atlantic species, O. atlanticus, corresponding to
      recognized biogeographic provinces, with divergences of d = 5.2-12.7% among the
      Caribbean, Brazilian, St. Helena/Ascension Island, Gulf of Guinea, and
      Azores/Cape Verde regions. The Atlantic phylogeny is consistent with Pliocene
      dispersal from the western to eastern Atlantic, and the depth of these
      separations (along with prior morphological comparisons) may indicate previously
      unrecognized species. The eastern Pacific species, O. steindachneri, is
      characterized by markedly less structure than O. atlanticus, with shallow
      mitochondrial DNA lineages (dmax = 2.7%) and haplotype frequency shifts between
      locations in the Sea of Cortez, Pacific Panama, Clipperton Island, and the
      Galapagos Islands. No concordance between genetic structure and biogeographic
      provinces was found for O. steincdachneri. We attribute the phylogeographic
      pattern in O. atlanticus to dispersal during the reorganization of Atlantic
      circulation patterns that accompanied the shoaling of the Isthmus of Panama. The
      low degree of structure in the eastern Pacific is probably due to unstable
      circulation and linkage to the larger Pacific Ocean basin. The contrast in
      genetic signatures between Atlantic and eastern Pacific blennies demonstrates how
      differences in geology and oceanography have influenced evolutionary radiations
      within each region.

PMID- 11327164
TI  - Holarctic phylogeography of Arctic charr (Salvelinus alpinus L.) inferred from
      mitochondrial DNA sequences.
AB  - This study evaluated mitochondrial DNA (mtDNA) sequence variation in a 552-bp
      fragment of the control region of Arctic charr (Salvelinus alpinus) by analyzing
      159 individuals from 83 populations throughout the entire range of the complex. A
      total of 89 (16.1%) nucleotide positions were polymorphic, and these defined 63
      haplotypes. Phylogenetic analyses supported the monophyly of the complex and
      assigned the observed haplotypes to five geographic regions that may be
      associated with different glacial refugia. Most notably, a formerly defined major
      evolutionary lineage (S. a. erythrinus) ranging from North America across the
      Arctic archipelago to the Eurasian continent has now been partitioned into the
      Arctic group and the newly identified Siberian group. The Beringian group, formed
      entirely by specimens assigned to S. malma (Dolly Varden), encompassed the area
      formerly assigned to S. a. taranetzi. The latter, due to a unique haplotype,
      became the basal member of the Arctic group. Overall, the S. alpinus complex
      reflects divergent evolutionary groups coupled with shallow intergroup
      differentiation, also indicated by an analysis of molecular variance that
      attributed 73.7% (P < 0.001) of the total genetic variance among groups. Time
      estimates, based on sequence divergence, suggest a separation of the major
      phylogeographic groups during early to mid-Pleistocene. In contrast, colonization
      of most of today's range started relatively recently, most likely late
      Pleistocene during the last retreat of ice sheets some 10,000-20,000 years ago.
      This time scale obviously is too shallow for detecting significant variation on a
      smaller scale using mtDNA markers. However, other studies using nuclear
      microsatellite DNA variation strongly suggested ongoing evolution within groups
      by revealing strong population-genetic substructuring and restricted gene flow
      among populations. Thus, Arctic charr could serve as a model organism to
      investigate the linkage between historical and contemporary components of
      phylogeographic structuring in fish, and, with a global perspective of the
      distribution of genetic variation as a framework, meaningful comparisons of charr
      studies at a smaller geographic scale will now be possible.

PMID- 11327165
TI  - Cladogenesis and loss of the marine life-history phase in freshwater galaxiid
      fishes (Osmeriformes: Galaxiidae).
AB  - Switches from migratory (diadromous) to nonmigratory (freshwater) life histories
      are known to have occurred repeatedly in some aquatic taxa. However, the
      significance of the loss of diadromy as an initiator for speciation remains
      poorly understood. The rivers of New Zealand's South Island house a species flock
      of recently derived nonmigratory galaxiid fishes known as the Galaxias vulgaris
      complex. Members of this complex are morphologically and genetically similar to
      the diadromous G. brevipinnis found in New Zealand and southeastern Australia. We
      hypothesised that South Island's G. vulgaris complex (at least 10 nonmigratory
      lineages) represents a number of independent radiations from a migratory G.
      brevipinnis stock, with repeated loss of diadromy. Sequence data were obtained
      for 31 ingroup samples (G. vulgaris complex and G. brevipinnis) plus four
      outgroup taxa. A well-resolved phylogeny based on 5039 base pairs of the
      mitochondrial genome suggests that diadromy has been lost on three separate
      occasions. Thus, speciation in these galaxiid fishes is partly an incidental
      phenomenon caused by switches from diadromous to nonmigratory strategies.
      However, much of the subsequent nonmigratory diversity is monophyletic,
      suggesting that drainage evolution (vicariance) has also played a major role in
      cladogenesis. Levels of sequence divergence among major ingroup lineages (1.6
      12.7%) suggest that the radiation is considerably older relative to Northern
      Hemisphere (postglacial) complexes of salmonid, osmerid, and gasterosteid fishes.
      Sympatric taxa are not monophyletic, suggesting that their coexistence reflects
      secondary contact rather than sympatric speciation. The monophyly of New Zealand
      G. brevipinnis is well supported, but both mitochondrial DNA and nuclear
      sequences indicate that G. brevipinnis is paraphyletic on an intercontinental
      scale. The divergence (maximum 11.5%) between Tasmanian and New Zealand G.
      brevipinnis, although large, supports marine dispersal rather than vicariance as
      the principle biogeographic mechanism on an intercontinental scale.

PMID- 11327166
TI  - Bumpus in the snake den: effects of sex, size, and body condition on mortality of
      red-sided garter snakes.
AB  - Huge breeding aggregations of red-sided garter snakes (Thamnophis sirtalis
      parietalis) at overwintering dens in Manitoba provide a unique opportunity to
      identify sources of mortality and to clarify factors that influence a snake's
      vulnerability to these factors. Comparisons of sexes, body sizes, and body
      condition of more than 1000 dead snakes versus live animals sampled at the same
      time reveal significant biases. Three primary sources of mortality were
      identified. Predation by crows, Corvus brachyrhynchos (590 snakes killed), was
      focussed mostly on small snakes of both sexes. Crows generally removed the
      snake's liver and left the carcass, but very small snakes were sometimes brought
      back to the nest. Suffocation beneath massive piles of other snakes within the
      den (301 dead animals) involved mostly small males and (to a lesser extent) large
      females; snakes in poor body condition were particularly vulnerable. Many
      emaciated snakes (n = 142, mostly females) also died without overt injuries,
      probably due to depleted energy reserves. These biases in vulnerability are
      readily interpretable from information on behavioral ecology of the snakes. For
      example, sex biases in mortality reflect differences in postemergence behavior
      and locomotor capacity, the greater attractiveness of larger females to males,
      and the high energy costs of reproduction for females.

PMID- 11327167
TI  - Geographic variation in antisnake tactics: the evolution of scent-mediated
      behavior in a lizard.
AB  - We used modern comparative methods to examine the evolution of scent-mediated
      antisnake behavior in the rock-dwelling velvet gecko (Oedura lesueurii). The
      selective agent is a snake species (broad-headed snake, Hoplocephalius
      bungaroides) that feeds primarily on velvet geckos by remaining sedentary in rock
      crevices for days or weeks, waiting to ambush lizards. The past and present
      distribution of this predator is well documented because of its threatened
      conservation status. We used this information to sample lizards from three
      populations distributed with snakes (sympatric) and three populations that appear
      never to have been distributed with snakes (allopatric) in each of two widespread
      but geographically distinct genetic groups of velvet gecko (as determined using
      allozyme electrophoresis). Wild-caught immature geckos from sympatric populations
      showed higher tongue-flick rates and stronger shifts in locomotion (increased
      duration of crawling and remaining stationary while pressed against the rock)
      toward snake-scented rocks than did lizards from allopatric populations. However,
      predation environment did not significantly affect a lizard's tendency to display
      other typical antisnake tactics such as tail waving or fleeing. These results
      were highly repeatable across the two sampled genetic groups of velvet gecko,
      despite demonstrable genetic divergence between groups. Experiments with
      hatchling lizards that had no experience with predators indicate that qualitative
      components of antisnake behaviors are probably inherited. The method of
      phylogenetically independent contrasts strongly suggests that the presence or
      absence of snakes has driven the evolution of behavior in velvet geckos.
      Collectively, these results provide support for an often suggested but
      speculative expectation that prey can adapt to predation pressure on a local
      scale.

PMID- 11327168
TI  - Major-histocompatibility-complex-associated variation in secondary sexual traits
      of white-tailed deer (Odocoileus virginianus): evidence for good-genes
      advertisement.
AB  - Good-genes hypotheses predict that development of secondary sexual characters can
      be an honest advertisement of heritable male quality. We explored this hypothesis
      using a cervid model (adult, male white-tailed deer, Odocoileus virginianus) to
      determine whether antler development could provide an honest signal of a male's
      genetic quality and condition to adversaries. We compared antler, morphometric,
      hormonal, and parasitic data collected from hunter-harvested deer to
      characteristics of the Mhc-DRB (Odvi), the most widely studied gene of the major
      histocompatibility complex (MHC) in Artiodactyla. We detected associations
      between genetic characteristics at Odvi-DRB and antler development and body mass,
      suggesting that antler development and body mass may be associated with pathogen
      resistance in deer and thus may be an honest signal of genetic quality. We also
      detected associations between Odvi-DRB characteristics and serum testosterone
      during the breeding season, suggesting that certain MHC characteristics may help
      deer cope with stresses related to breeding activity. In addition, we observed a
      negative relationship between degree of antler development and overall abundance
      of abomasal helminths. Our observations provide support for the hypothesis that
      antler development in white-tailed deer is an honest signal of quality.

PMID- 11327169
TI  - Calling behavior and directional hybridization between two toads (Bufo
      microscaphus x B. woodhousii) in Arizona.
AB  - Male calling effort and mitochondrial DNA (mtDNA) variation were examined in a
      breeding chorus of toads from a hybrid zone between Bufo microscaphus and B.
      woodhousii in central Arizona. The chorus comprised 50 B. microscaphus and 17
      hybrids, identified on the basis of morphology and advertisement calls; no pure
      B. woodhousii were observed. Males produced advertisement calls throughout the
      early evening, even when relatively large numbers of males (>50) were present at
      the chorus; active searching and satellite tactics were not observed. Calling
      efforts (call duration x call rate) of hybrids (23.9%, n = 8) and B. microscaphus
      (24.9%, n = 19) were similar and comparable to call efforts of B. woodhousii
      (21.9%, n = 10) from a different site. Moreover, repeatabilities of calling
      effort were significant (r = 0.45) for hybrid males, but not for B. microscaphus
      and B. woodhousii. Thus, calling behavior of hybrid males was neither
      significantly reduced nor more variable than that of their parental species. The
      distribution of mtDNA haplotypes revealed directional introgression is occurring
      between male B. microscaphus and female B. woodhousii: All 17 hybrids possessed
      B. woodhousii mtDNA. The proximate mechanism driving hybridization appears to
      involve common male (B. microscaphus) and rare female (B. woodhousii) matings as
      B. woodhousii expands its range.

PMID- 11327170
TI  - Female preference for male saliva: implications for sexual isolation of Mus
      musculus subspecies.
AB  - We studied the effects of a single genetic change on a complex mammalian behavior
      using animals congenic for two variants of Abpa, the gene for the alpha subunit
      of mouse salivary androgen-binding protein (ABP), in two-way preference tests.
      Females exhibited a preference for investigating salivas of males of their own
      genetic type of ABP but not for urines of either type of male. This preference
      behavior is consistent for samples of mice from geographically diverse
      populations of Mus musculus domesticus and M. m. musculus. These findings provide
      an explanation for the observation that this gene is evolving under strong
      selection.

PMID- 11327171
TI  - Sex-biased dispersal in a migratory bat: a characterization using sex-specific
      demographic parameters.
AB  - We studied the noctule bat (Nyctalus noctula), in which the mitochondrial F(ST)
      is about 10 times that revealed by nuclear markers, to address two questions. We
      first verified whether random dispersal of one sex is compatible with highly
      contrasted mitochondrial and nuclear population structures. Using computer
      simulations, we then assessed the power of multilocus population differentiation
      tests when the expected population structure departs only slightly from panmixia.
      Using an island model with sex-specific demographic parameters, we found that
      random male dispersal is consistent with the population structure observed in the
      noctule. However, other parameter combinations are also compatible with the data.
      We computed the minimum sex bias in dispersal (at least 69% of the dispersing
      individuals are males), a result that would not be available if we had used more
      classical population genetic models. The power of multilocus population
      differentiation tests was unexpectedly high, the tests being significant in
      almost 100% of the replicates, although the observed population structure infered
      from nuclear markers was extremely low (F(ST) = 0.6%).

PMID- 11327172
TI  - Data needs for studies of competition in market areas. Overview of the special
      supplement issue.

PMID- 11327173
TI  - Organizational economics and health care markets.
AB  - As health policy emphasizes the use of private sector mechanisms to pursue public
      sector goals, health services research needs to develop stronger conceptual
      frameworks for the interpretation of empirical studies of health care markets and
      organizations. Organizational relationships should not be interpreted exclusively
      in terms of competition among providers of similar services but also in terms of
      relationships among providers of substitute and complementary services and in
      terms of upstream suppliers and downstream distributors. This article illustrates
      the potential applicability of transactions cost economics, agency theory, and
      organizational economics more broadly to horizontal and vertical markets in
      health care. Examples are derived from organizational integration between
      physicians and hospitals and organizational conversions from nonprofit to for
      profit ownership.

PMID- 11327174
TI  - Competition in hospital and health insurance markets: a review and research
      agenda.
AB  - OBJECTIVES: To review the empirical literature on the effects of selective
      contracting and hospital competition on hospital prices, travel distance,
      services, and quality; to review the effects of managed care penetration and
      competition on health insurance premiums; and to identify areas for further
      research. PRINCIPAL FINDINGS: Selective contracting has allowed managed care
      plans to obtain lower prices from hospitals. This finding is generalizable beyond
      California and is stronger when there is more competition in the hospital market.
      Travel distances to hospitals of admission have not increased as a result of
      managed care. Evidence on the diffusion of technology in hospitals and the extent
      to which hospitals have specialized as a result of managed care is mixed. Little
      research on the effects on quality has been undertaken, but preliminary evidence
      suggests that hospital quality has not declined and may have improved. Actual
      mergers in the hospital market have not affected hospital prices. Much less
      research has been focused on managed care markets. Greater market penetration and
      greater competition among managed care plans are associated with lower managed
      care premiums. Greater HMO penetration appears to be much more effective than PPO
      penetration in leading to lower premiums. While workers are willing to change
      plans when faced with higher out-of-pocket premiums, there is little evidence of
      the willingness of employers to switch plan offerings. Preliminary evidence
      suggests that greater managed care penetration has led to lower overall employer
      premiums, but the results differ substantially between employers with and without
      a self-insured plan. CONCLUSIONS: Much more research is needed to examine all
      aspects of managed care markets. In hospital markets, particular attention should
      be focused on the effects on quality and technology diffusion.

PMID- 11327175
TI  - Measuring competition in health care markets.
AB  - OBJECTIVE: Measuring competition is increasingly important for analysis of health
      care markets and policies. Measurement of competition in health care is made
      complex by the breadth of potential issues under study, by the lack of necessary
      data, and by rapid changes in health care financing and delivery. This study
      reviews key issues in the measurement of competition and is designed to
      familiarize researchers and policymakers interested in competition measurement,
      but not steeped in its practice, with key concepts, data sources, and ways of
      adapting measures to fit ongoing changes in health care markets. PRINCIPAL
      FINDINGS: Attention to several key issues will strengthen measurement. Important
      components of successful measurement are: careful identification of the products
      and market areas for study; selection of Herfindahl-Hirschman or other indices to
      fit the issues being considered; consideration of econometric problems, like
      endogeneity, with common measures; and attention to the ways that current
      marketplace changes, like growth in managed care, affect the performance of
      classic measures. Data needed for constructing measures are also frequently
      scarce, insufficient, or both. Measurement could be improved with access to
      better data.

PMID- 11327176
TI  - Studying the effects of health plan competition: are available data resources up
      to the task?
AB  - OBJECTIVES: To review the availability of data sources to study health plan
      competition in the United States. DATA SOURCES: The literature on health plan
      competition was reviewed. Possible data sources to study health plan competition
      were evaluated. Experts in the field of health plan competition were contacted
      about their knowledge of existing data sources. Principal Findings. There is much
      more quantitative data available on HMO plans than on other types of health plans
      that are growing in popularity, such as PPOs. A key source for health plan data,
      state health insurance filings, lacks information on beneficiaries in non-HMO
      plans. Data on health plan quality is growing. In addition, case studies of
      particular markets is providing useful qualitative information on the dynamics of
      the health plan industry. CONCLUSIONS: The fragmentation of the health care
      market and the hesitancy of governments and private organizations to provide
      detailed information across markets and providers creates serious obstacles to
      the study of health plan competition.

PMID- 11327177
TI  - Data sharing and dissemination strategies for fostering competition in health
      care.
AB  - OBJECTIVES: To introduce the concept of common models for data sharing and
      dissemination, highlight the current operational, technical, and political issues
      surrounding existing data sharing and dissemination initiatives in a health care
      market, and suggest an ideal model for future data initiatives. DATA
      SOURCES/STUDY SETTING: A literature review and case studies of existing data
      sharing and dissemination initiatives that promote the collection and use of
      comparative information on provider cost and quality. PRINCIPAL FINDINGS: Three
      broad types of common models for data sharing and dissemination have evolved over
      the past decade or so: (1) provider-initiated initiatives developed through
      collaboration among providers of health care; (2) purchaser-initiated activities
      driven by a coalition of purchasers; and (3) indirect collaboration-data-sharing
      initiatives between providers and purchasers with a significant facilitating or
      regulating role by a third group of stakeholders. The success of a data-sharing
      and dissemination strategy is determined by how the complex operational,
      technical, and political issues are addressed. General principles by which a
      health data initiative might abide include the following: standardized databases
      as the physical foundation, indicators that reflect the changing market; linkages
      between and across data sets for comprehensive and complete data; economic value;
      policy relevance; use of evolving technologies to collect, integrate, and
      disseminate data; and stakeholder support. CONCLUSIONS: Regulatory solutions
      alone will not overcome the complex political and technical challenges to data
      sharing and dissemination. The "ideal" model or process nurturing a market for
      health care information will incorporate compromise and negotiation to address
      the issues of data ownership and proprietary concerns, therefore securing the
      necessary political and financial support of the private sector.

PMID- 11327178
TI  - Conducting research on the Medicare market: the need for better data and methods.
AB  - OBJECTIVE: To highlight data limitations, the need to improve data collection,
      the need to develop better analytic methods, and the need to use alternative data
      sources to conduct research related to the Medicare program. Objectives were
      achieved by reviewing existing studies on risk selection in Medicare HMOs,
      examining their data limitations, and introducing a new approach that circumvents
      many of these shortcomings. DATA SOURCES: Data for years 1995-97 for five states
      (Arizona, Florida, Massachusetts, New York, and Pennsylvania) from the Healthcare
      Cost and Utilization Project (HCUP) State Inpatient Databases (SIDs), maintained
      by the Agency for Healthcare Research and Quality; and the Health Care Financing
      Administration's Medicare Managed Care Market Penetration Data Files and Medicare
      Provider Analysis and Review Files. STUDY DESIGN: Analysis of hospital
      utilization rates for Medicare beneficiaries in the traditional fee-for-service
      (FFS) Medicare and Medicare HMO sectors and examination of the relationship
      between these rates and the Medicare HMO penetration rates. PRINCIPAL FINDINGS:
      Medicare HMOs have lower hospital utilization rates than their FFS counterparts,
      differences in utilization rates vary across states, and HMO penetration rates
      are inversely related to our rough measure of favorable selection. CONCLUSIONS:
      Substantial growth in Medicare HMO enrollment and the implementation of a new
      risk-adjusted payment system have led to an increasing need for research on the
      Medicare program. Improved data collection, better methods, new creative
      approaches, and alternative data sources are needed to address these issues in a
      timely and suitable manner.

PMID- 11327179
TI  - Alcohol use and problems at colleges banning alcohol: results of a national
      survey.
AB  - OBJECTIVE: This study examines student alcohol use and associated problems,
      including drinking and driving, at U.S. colleges that ban alcohol for all
      students on campus. METHOD: A nationally representative sample of students (N =
      11,303, 61% women) attending U.S. colleges completed questionnaires regarding
      alcohol use and related behaviors in the spring of 1999. The responses of 2,252
      students at 19 ban schools were compared with those of 9,051 students at 76
      nonban schools. RESULTS: Students at ban colleges were 30% less likely to be
      heavy episodic drinkers and more likely to abstain from alcohol. The lower rates
      of heavy episodic drinking apply to students whether or not they were heavy
      episodic drinkers in high school. However, among drinkers, students at ban
      schools engaged in as much extreme drinking as drinkers at schools that do not
      ban alcohol and experienced the same rate of alcohol-related problems. At schools
      that ban alcohol, fewer students experienced secondhand effects of the drinking
      of others than did students at nonban schools. Students at ban schools were not
      more likely to drink and drive than were students at nonban schools. CONCLUSIONS:
      A campus ban on alcohol may support abstention from alcohol use and reduce heavy
      episodic drinking and the associated secondhand effects in college. Since this is
      a correlational study, we cannot determine whether the lower rates of heavy
      episodic drinking are due to the ban or to other factors (e.g., self-selection of
      students to these schools). Ban schools do not enroll fewer high school heavy
      episodic drinkers.

PMID- 11327180
TI  - Trends in public opinion on alcohol policy measures: Ontario 1989-1998.
AB  - OBJECTIVE: This article presents trend data concerning public opinion on alcohol
      policy in the Canadian province of Ontario over a 10-year period (1989-98),
      highlights the currently debated issue of private venues for retail alcohol sales
      and assesses correspondence between public opinion and actual and proposed policy
      decisions. METHOD: Selected policy-related items from nine probability surveys on
      representative samples of male and female Ontario adults (range of unweighted n
      's: 953 to 1,947) were analyzed by means of logistic regression. RESULTS: We
      found strong support for the status quo for a number of items, including beer and
      liquor store hours, corner store sales and taxes. Across all years, less than 6%
      of the total sample wanted to lower the legal drinking age. Over time, a linear
      trend showed a gradual but not entirely consistent development of attitudes among
      the Ontario public, favoring relaxation of some controls. However, contrary to
      this trend, disapproval of retail sales in corner stores increased significantly
      from 1992 to 1996. Demographic breakdown shows that relaxation of controls is
      most favored by those who report consumption of five or more drinks per occasion
      at least weekly over the past 12 months, and most strongly opposed by women and
      nondrinkers. Of those who seldom or never consume five or more drinks per
      occasion, the majority express satisfaction with the status quo. CONCLUSIONS:
      These data call into question the suitability of changes in alcohol policy that
      would diminish controls. It is of particular interest that there seems to be
      little public support for privatization proposals in the province. Public opinion
      against comer store sales of alcoholic beverages increased over time.

PMID- 11327181
TI  - The dimensionality of alcohol abuse and dependence: a multivariate analysis of
      DSM-IV symptom items in the National Longitudinal Survey of Youth.
AB  - OBJECTIVE: This article examines the factor structure of 22 symptom items used to
      configure the criteria of DSM-IV (Diagnostic and Statistical Manual of Mental
      Disorders, Fourth Edition) alcohol abuse and dependence and relates the factor
      structure to background characteristics. METHOD: Data for this study were drawn
      from the National Longitudinal Study of Labor Market Experience in Youth (NLSY).
      The symptom items were related to the covariates using the statistical technique
      of structural equation modeling generalized to dichotomous outcomes. The present
      model is a special case of structural equation modeling, a multiple causes and
      multiple indicators (MIMIC) model, in which one or more latent variables (i.e.,
      alcohol abuse and dependence) intervene between a set of observed background
      variables predicting a set of observed response variables (i.e., DSM-IV symptom
      items). RESULTS: The results of the structural equation analysis provide further
      support for two dimensions underlying the DSM-IV symptom items. Although the two
      factor dimension bore a strong resemblance to the DSM-IV conceptions of abuse and
      dependence, there were notable differences in the item content of the symptom
      items for each dimension. The dependence dimension drew upon items related to the
      abuse criteria for continued drinking despite social problems and recurrent
      drinking resulting in failure to fulfill role obligations. The abuse dimension
      drew upon items related to the abuse criterion for hazardous drinking and the
      dependence criterion for larger amounts over time. The two factors were shown to
      have different relationships to the background variables. Alcohol dependence was
      related to family history of alcoholism and educational status. Age was not
      related to dependence and inversely related to alcohol abuse. CONCLUSIONS:
      Findings from this study replicate the two-dimensional model for DSM-IV criteria
      found in other studies and provide further support for the validity of alcohol
      dependence in general population samples. A major implication of the factor
      structure in the present study relates to the different classification of cases
      that would otherwise be obtained with DSM-IV criteria. These departures were
      shown to affect abuse, which retained only 40% of DSM-IV diagnoses, more strongly
      than dependence, which retained 91% of DSM-IV diagnoses.

PMID- 11327182
TI  - Progression of alcohol problems in a Navajo sample.
AB  - OBJECTIVE: This study tested the cross-cultural applicability of Jellinek's
      progression in a sample of Navajo men and women. Jellinek (1952) described a
      predictable progression of alcoholism that continues to be used widely in
      treatment, but it is unclear whether this pattern is consistent across cultures
      and genders. METHOD: The sample consisted of 99 Navajo (67 men and 32 women) who
      were undergoing detoxification in a secure facility. Participants were asked
      about the quantity and frequency of their drinking as well as other drinking
      experiences. Their level of cultural identification was also assessed. RESULTS:
      Of the 46 events established by Jellinek, the order of progression for the Navajo
      sample was modestly correlated (r(s) = .41, p = .005, 17% shared variance) with
      that for Jellinek's white men. The correlation of Jellinek's sample with the
      Navajo men was slightly larger (r(s) = .48, p = .001, 23% shared variance) than
      that of the whole sample; however, the comparison with Navajo women resulted in a
      near zero correlation (r(s) = .06, p = .705, 4% shared variance). CONCLUSIONS: In
      the context of studies from other cultures, these data suggest convergence
      decreases as the studied sample deviates culturally from Jellinek's sample of
      U.S. white men. These data question the cross-cultural applicability of this
      popular model of progression of alcoholism.

PMID- 11327183
TI  - A six-year prospective study of pathways toward drug use in adolescent boys with
      and without a family history of a substance use disorder.
AB  - OBJECTIVE: The purpose of this study was to test a developmental model of drug
      use in male adolescents. The model postulates that low executive functioning and
      a difficult temperament are related to aggression and affiliations with
      delinquent peers which, in turn, are related to elevated drug use. METHOD: Boys
      (N = 187) with and without a family history of a substance use disorder (SUD)
      were followed over a 6-year period. Executive functioning and temperament were
      measured at age 10-12, aggression and affiliations with delinquent peers were
      assessed at age 12-14 and drug use was measured at age 16. RESULTS: Low executive
      functioning and a difficult temperament were related to increased aggression and
      affiliations with delinquent peers. These latter variables were related to
      increased drug use. Furthermore, the relation between difficult temperament and
      drug use was fully mediated by aggression and affiliations with delinquent peers.
      CONCLUSIONS: Drug abuse prevention efforts may benefit from clinical
      interventions aimed at strengthening executive functioning, regulating
      temperament and improving socialization strategies in antisocial children.

PMID- 11327184
TI  - The social predictors of adolescent alcohol misuse: a test of the social
      development model.
AB  - OBJECTIVE: This study was conducted to investigate the ability of the social
      development model (SDM) to predict alcohol misuse at age 16 and to investigate
      the ability of the SDM to mediate the effects of alcohol use at age 14 on alcohol
      misuse at age 16. METHOD: The sample of 807 (411 males) is from the longitudinal
      panel of the Seattle Social Development Project which, in 1985, surveyed all
      consenting fifth-grade students from 18 elementary schools serving high-crime
      neighborhoods in Seattle, Washington. Alcohol use was measured at age 14,
      predictors of alcohol misuse were measured at age 15 and alcohol misuse was
      measured at age 16. Structural equation modeling was used to examine the fit of
      the model to the data. RESULTS: All factor loadings were highly significant and
      the measurement model achieved a good fit with the data (Comparative Fit Index
      [CFI] = 0.93). A second-order structural model fit the data well (CFI = 0.91) and
      also explained 45% of the variance in alcohol misuse at age 16. The SDM partially
      and significantly mediated the direct effect of age-14 alcohol use on age-16
      alcohol misuse. CONCLUSIONS: The risk and protective processes specified by the
      SDM serve as potential targets for the prevention or reduction of adolescent
      alcohol misuse.

PMID- 11327185
TI  - Drinking to cope, emotional distress and alcohol use and abuse: a ten-year model.
AB  - OBJECTIVE: This study examines the ability of baseline drinking to cope to
      predict drinking behavior across an ensuing 10-year period. In addition, it
      examines whether a propensity to consume alcohol to cope with stressors
      strengthens the link between emotional distress and drinking behavior. METHOD:
      The study uses survey data from a baseline sample of 421 adults (54% women)
      assessed four times over a 10-year period (i.e., baseline and 1-, 4- and 10-year
      follow-ups). RESULTS: Baseline drinking to cope was associated with more alcohol
      consumption and drinking problems at all four observations across the 10-year
      interval. Baseline drinking to cope also predicted increases in both alcohol
      consumption and drinking problems in the following year. Moreover, change in
      drinking to cope was positively linked to changes in both alcohol consumption and
      drinking problems over the interval. Individuals who had a stronger propensity to
      drink to cope at baseline showed a stronger link between both anxiety and
      depressive symptoms and drinking outcomes. CONCLUSIONS: Findings demonstrate the
      power of alcohol-related coping strategies in predicting long-term drinking
      behavior and they illustrate one way in which such coping is linked to alcohol
      use and abuse. More broadly, they underscore the importance of considering
      individual differences in emotion-based theories of drinking behavior.

PMID- 11327186
TI  - Examining developmental trajectories in adolescent alcohol use using piecewise
      growth mixture modeling analysis.
AB  - OBJECTIVE: This study examined issues of heterogeneity in multiple stage
      development as it corresponds to qualitatively different developmental
      trajectories in alcohol use during adolescence. METHOD: Using a piecewise growth
      mixture modeling methodology, a two-piece growth model capturing growth
      trajectories in adolescent alcohol use from middle school (Grades 6 through 8) to
      high school (Grades 9 through 12) was examined (N = 179; 54% male). It was
      hypothesized that (1) two stages of alcohol use development with varying
      trajectories would exist in these data (the first corresponding to development
      during middle school, followed by a second stage of continuing growth during high
      school) and (2) there would be multiple growth trajectories (subgroups) of
      alcohol use in the stage-wise development, with varying effects in initial
      alcohol use and growth rates of alcohol use. RESULTS: Results indicated the
      tenability of the two-piece growth model of alcohol use with heterogeneity in the
      population comprising two distinct latent developmental trajectory classes. Class
      1, with a high initial status of alcohol use at Grade 6, showed an upward
      increase in trajectory only during high school. Class 2, with a low initial
      status of alcohol use at Grade 6, showed a linear increase in middle school with
      a second growth spurt at high school entry and continuity in growth throughout
      the high school years. Analyses, incorporating time-invariate covariates,
      indicated varying influences of gender, early levels of deviant behavior, family
      structure (single vs two parent), peer encouragement and parent disapproval of
      alcohol use, and adolescent deviant behavior upon high school entry, on the two
      trajectory classes. Results also showed effects of the identified trajectories,
      with varying magnitudes, on later substance use in young adulthood, with Class 1
      showing the strongest continuity in later substance use. CONCLUSIONS: Findings
      suggest heterogenous development of alcohol use in the adolescent population,
      associated with varying background and covariate influences. In addition, this
      heterogeneity is linked to alcohol and other substance use in young adulthood.

PMID- 11327187
TI  - How effective is alcoholism treatment in the United States?
AB  - OBJECTIVE: Following in the footsteps of several prior attempts, this review
      seeks a meaningful and data-based answer to the common question of how people
      fare, on average, after being treated for alcoholism (broadly defined as alcohol
      use disorders). METHOD: Findings from seven large multisite studies were combined
      to derive estimates of the average effectiveness of alcoholism treatment. To
      provide common outcome measures, conversion equations were used to compute
      variables not reported in the original studies. RESULTS: During the year after
      treatment, 1 in 4 clients remained continuously abstinent on average, and an
      additional 1 in 10 used alcohol moderately and without problems. During this
      period, mortality averaged less than 2%. The remaining clients, as a group,
      showed substantial improvement, abstaining on 3 days out of 4 and reducing their
      overall alcohol consumption by 87%, on average. Alcohol-related problems also
      decreased by 60%. CONCLUSIONS: About one third of clients remain asymptomatic
      during the year following a single treatment event. The remaining two thirds
      show, on average, large and significant decreases in drinking and related
      problems. This substantial level of improvement in "unremitted" clients tends to
      be overlooked when outcomes are dichotomized as successful or relapsed.

PMID- 11327188
TI  - Longitudinal relationship between the alcohol warning label and alcohol
      consumption.
AB  - OBJECTIVE: The present study reports the longitudinal relationship between
      alcohol warning label exposure and alcohol consumption among adolescents. METHOD:
      In-school surveys assessed adolescents at three annual time points beginning in
      tenth grade. There were 649 participants measured at all three time points; 51%
      were female. Four effects were the focus of the covariance structure, latent
      growth analysis of these data: (1) an exposure effect, whereby earlier alcohol
      use leads to more exposure to the warning label; (2) a deterrent effect, whereby
      earlier alcohol warning label exposure reduces subsequent alcohol consumption;
      (3) a harmful effect, corresponding to a positive relationship between early
      exposure and subsequent consumption; and (4) both exposure and deterrent effects
      operating at the same time. RESULTS: There was a statistically significant
      exposure effect such that earlier alcohol use was associated with later exposure
      to the warning. The association between earlier alcohol warning label exposure
      and subsequent alcohol use was generally negative but not statistically
      significant, suggesting that the warning did not affect alcohol consumption.
      CONCLUSIONS: These results suggest that the alcohol warning label is having the
      intended effect as described in the law requiring the warning. That is, it is
      informing and reminding persons of the risks associated with alcohol use. The
      warning does not appear to significantly increase or decrease alcohol
      consumption.

PMID- 11327189
TI  - Impact of normative feedback on problem drinkers: a small-area population study.
AB  - OBJECTIVE: As many as one in four adults in North America experiences some
      problems due to alcohol consumption. Although most of these problem drinkers do
      not have concerns that are severe enough to merit formal treatment, such drinking
      has large economic costs and can place the drinker at risk for long-term negative
      health and social consequences. The present study evaluated a minimal
      intervention that used normative feedback about population drinking to motivate
      changes in alcohol use. METHOD: An intervention pamphlet was mailed to over 6,000
      households in Toronto, randomized by block from a region containing almost 10,000
      households. In the month after the mailing, a general population survey was
      conducted in the region to assess alcohol use. RESULTS: Respondents from
      households receiving normative feedback (n = 472) reported significantly lower
      alcohol use than controls (n = 225), but this effect occurred only among
      respondents who met an objective criterion for problem drinking and who perceived
      some risk associated with their drinking. CONCLUSIONS: Viewed from a public
      health perspective, normative feedback interventions have the potential for a
      significant payoff because they can be provided at low cost and to problem
      drinkers who might ordinarily never access any treatment services.

PMID- 11327190
TI  - Verbal and nonverbal fluency in children with heavy prenatal alcohol exposure.
AB  - OBJECTIVE: Executive function deficits, including verbal fluency, have been
      documented in children with histories of prenatal alcohol exposure. Whereas
      nonverbal fluency impairments have been reported in adults with such exposure,
      these abilities have not been tested in children. Deficits in both verbal and
      nonverbal fluency were predicted and assessed in children and adolescents with
      histories of heavy prenatal alcohol exposure. METHOD: There was a total of 28
      (54% female) subjects; children with heavy prenatal alcohol exposure with (n =
      10) and without (n = 8) fetal alcohol syndrome (FAS) were compared to nonexposed
      controls (n = 10) on the design and verbal fluency measures from the Delis-Kaplan
      Executive Function System. Both fluency measures consist of three conditions,
      including a new set-shifting task. All tests require the generation of multiple
      responses within both rule and time constraints. RESULTS: Data were analyzed
      using repeated measures analyses of variance and hierarchical regression
      analyses. Compared to controls, children with heavy prenatal alcohol exposure
      with and without FAS displayed deficits in both fluency domains, but did not
      differ from each other. In addition, prenatal alcohol exposure was a significant
      predictor of performance on the set-shifting design fluency task above and beyond
      performance on more traditional fluency tasks. IQ was not a significant predictor
      for the traditional or set-shifting fluency measures, whereas diagnostic group
      remained a significant predictor when IQ was included in the model. CONCLUSIONS:
      This study adds to the literature on the integrity of executive functions in
      children with heavy prenatal alcohol exposure, documenting fluency impairment in
      both verbal and nonverbal domains. It is important to note that these impairments
      were demonstrated in higher functioning alcohol-exposed children, both with and
      without FAS, and that diagnostic group explained such deficiencies above and
      beyond general intellectual ability.

PMID- 11327191
TI  - A test of the appraisal-disruption model of alcohol and stress.
AB  - OBJECTIVE: Faced with a large body of contradictory findings, investigators have
      begun to propose cognitive factors that moderate the effects of alcohol on
      stress. We tested the hypothesis, stemming from the appraisal-disruption model
      (ADM), that alcohol would be more likely to reduce stress when consumed prior to
      exposure to a stressor than when consumed following exposure. METHOD: Male and
      female social drinkers (N = 169, 85 men) with or without a parental history of
      alcoholism were recruited using separate structured clinical interviews with the
      participant and with a biological parent. Participants drank a moderate dose of
      alcohol or a placebo in one of two temporal sequences. Stress was induced by
      asking participants to present a self-disclosing speech about their physical
      appearance. Stress responses were assessed using four types of measures: self
      reported anxiety, pulse rate, facial expression associated with negative affect
      and threat-related interference on a color-naming task. RESULTS: Alcohol was
      generally more likely to attenuate stress responses when initial exposure to a
      social stressor followed drinking than when it preceded drinking. CONCLUSIONS:
      Findings were consistent with predictions stemming from the ADM. Alcohol appears
      to be more likely to reduce stress when initial stress appraisal occurs during
      intoxication. In contrast, when initial appraisal occurs prior to drinking,
      alcohol is less effective in attenuating stress.

PMID- 11327192
TI  - Nonresponse in a follow-up to a representative telephone survey of adult
      drinkers.
AB  - OBJECTIVE: Examined predictors of nonresponse among respondents who agreed to
      receive a follow-up questionnaire on alcohol use after participating in a
      representative telephone survey, and among respondents who did and did not return
      the follow-up questionnaire. METHOD: A total of 2,072 (52.2% female) respondents
      to a representative monthly telephone survey were assessed on sociodemographic
      variables and alcohol use. Respondents were asked whether they would be willing
      to fill out an additional mailed questionnaire on alcohol use and attitudes
      toward drinking. Almost half (n = 956; 46%) of respondents agreed to participate
      in the follow-up survey; 430 (45%) of those individuals completed and returned
      the questionnaire. RESULTS: Agreement to receive the follow-up questionnaire was
      unrelated to alcohol use. Regarding gender, men were 1.42 times more likely than
      women to exhibit nonresponse in returning the follow-up questionnaire (95% CI:
      1.08-1.42). After adjusting for the impact of demographic factors, respondents
      who consumed alcohol at least once per week were 1.43 times more likely than
      respondents who drank less frequently to exhibit nonresponse in returning the
      questionnaire (95% CI: 1.05-1.93). Respondents who consumed five or more standard
      drinks at least once per week were 1.83 times more likely to exhibit nonresponse
      in returning the questionnaire, compared with respondents who engaged in heavy
      drinking less frequently (95% CI: 1.15-2.92). CONCLUSIONS: Mailout questionnaires
      following a representative telephone survey may bias samples toward obtaining
      fewer men, fewer weekly drinkers and fewer heavier drinkers. Although the
      magnitude of these biases were relatively small, epidemiological studies on
      alcohol use may wish to oversample men and heavier drinkers in follow-up studies
      recruiting from population surveys.

PMID- 11327193
TI  - Help-seeking timeline followback for problem drinkers: preliminary comparison
      with agency records of treatment contacts.
AB  - OBJECTIVE: A pilot study assessed the utility of the Timeline Followback (TLFB)
      method to collect information on help seeking. METHOD: Using the TLFB method, 34
      clients (26 men) who had attended at least one session of an outpatient alcohol
      treatment program reported on treatment contacts, including any supplemental
      services (e.g., psychiatric care). TLFB reports of help seeking at that agency
      were compared with agency records of treatment contacts. RESULTS: Clients
      reported on their help-seeking behavior for a period of approximately 8 months
      after they had completed an initial assessment for the outpatient treatment. With
      regard to the number of outpatient sessions they attended, intraclass
      correlations and equivalence testing showed that the TLFB data were comparable to
      the agency records of treatment contacts. Analysis of week-to-week correspondence
      of the presence or absence of help-seeking episodes showed good agreement between
      TLFB and the agency records for most participants, although there was substantial
      variation. Degree of correspondence was not associated with the length of the
      recall period or individual differences (e.g., drinking pattern). Older
      participants, however, tended to have lower week-to-week concordance than did
      younger participants. CONCLUSIONS: These data provide preliminary support for the
      utility of a help-seeking TLFB instrument to assess addiction- and mental health
      related contacts. This instrument may be especially useful in research in which
      collecting temporal patterns of help seeking is of interest (e.g., in studies
      examining factors influencing the delay in help seeking after relapse).

PMID- 11327194
TI  - Monthly variations in self-reports of alcohol consumption.
AB  - OBJECTIVE: This study examines monthly variation in reports of recent alcohol
      consumption behavior. METHOD: Telephone survey data collected by the Behavioral
      Risk Factor Surveillance System were used to measure self-reports of drinking and
      heavy episodic drinking in the 30 days before the interview. The sample (N =
      57,758) comprised cases collected in six states in 5 selected years. Monthly
      variability in self-reported alcohol consumption was evaluated by logistic
      regression analysis, using "deviation from means coding" for the month of
      interview, with background variables and year of interview controlled and state
      level clustering adjusted. RESULTS: Adults were significantly more likely to
      report past 30-day alcohol consumption when interviewed during the month of
      January and less likely to report consumption when interviewed during March.
      Respondents were also more likely to report heavy episodic drinking during the
      month of July. Despite large differences in alcohol consumption between male and
      female participants, these seasonal patterns were essentially the same for both
      genders. CONCLUSIONS: The findings suggest that assessments of alcohol
      consumption that do not consider seasonal variation may be biased. In order to
      minimize this bias, it is recommended that researchers avoid collecting data only
      during these particular times of the year or extend the data collection interval
      and control for seasonal variability.

PMID- 11327195
TI  - The erythromycin breath test for the prediction of drug clearance.
AB  - The erythromycin breath test (EBT) is a putative probe of cytochrome P450 (CYP)
      3A4 activity in vivo. Therefore, the EBT might prove useful for the
      individualisation of doses of drugs that have a low therapeutic window (for
      example the immunosuppressants or cytotoxics) and are metabolised by CYP3A4.
      However, there is a lack of consensus as to how the EBT should be used to predict
      total body clearance (CL), and the results so far have been largely
      disappointing. We argue that the required assumption that individuals produce 5
      mmol of CO2/min per m2 at rest is one of the problems with the existing EBT, as
      the literature suggests significant variability and possible gender differences
      in this parameter. An examination of the EBT with a simple compartment model
      suggests that alternative parameters could be more useful in the prediction of
      CL. In particular, there is theoretical support for the use of the time-point at
      which breath radioactivity is maximal (tmax) as a correlate for CL. This is in
      agreement with our recent study of the pharmacokinetics of erythromycin in
      patients with cancer.

PMID- 11327196
TI  - The gut as a barrier to drug absorption: combined role of cytochrome P450 3A and
      P-glycoprotein.
AB  - Intestinal phase I metabolism and active extrusion of absorbed drug have recently
      been recognised as major determinants of oral bioavailability. Cytochrome P450
      (CYP) 3A, the major phase I drug metabolising enzyme in humans, and the multidrug
      efflux pump, P-glycoprotein, are present at high levels in the villus tip of
      enterocytes in the gastrointestinal tract, the primary site of absorption for
      orally administered drugs. The importance of CYP3A and P-glycoprotein in limiting
      oral drug delivery is suggested to us by their joint presence in small intestinal
      enterocytes, by the significant overlap in their substrate specificities, and by
      the poor oral bioavailability of joint substrates for these 2 proteins. These
      proteins are induced or inhibited by many of the same compounds. A growing number
      of preclinical and clinical studies have demonstrated that the oral
      bioavailability of many CYP3A and/or P-glycoprotein substrate drugs can be
      increased by concomitant administration of CYP3A inhibitors and/or P-glycoprotein
      inhibitors. We believe that further understanding the physiology and biochemistry
      of the interactive nature of intestinal CYP3A and P-glycoprotein will be
      important in defining, controlling, and improving oral bioavailability of CYP3A/P
      glycoprotein substrates.

PMID- 11327197
TI  - Comparative pharmacokinetics and pharmacodynamics of the newer fluoroquinolone
      antibacterials.
AB  - A number of new fluoroquinolone antibacterials have been released for clinical
      use in recent years. These new agents exhibit enhanced activity against Gram
      positive organisms while retaining much of the Gram-negative activity of the
      earlier agents within the same class. The pharmacokinetics of most of these
      agents are well described including serum pharmacokinetics, tissue and fluid
      distribution, and pharmacokinetics in renal and hepatic disease. When compared
      with earlier agents within this class (i.e. ciprofloxacin), the newer agents
      retain the wide distribution characteristics; however, they exhibit a more
      prolonged elimination, which, in part, supports single daily administration for
      these agents. Based on their predominant renal elimination, dosage adjustment is
      necessary in the presence of renal disease for ciprofloxacin, levofloxacin,
      gatifloxacin and sitafloxacin. Drug interactions, particularly with multivalent
      cations (calcium/aluminium-containing antacids and iron products), remain a
      problem for the newer agents, resulting in reduced absorption requiring separate
      administration times to maximise bioavailability. However, the newer agents do
      not appear to interfere significantly with the cytochrome P450 system, thus
      minimising the potential for interactions with other drugs metabolised by this
      system. The pharmacodynamic properties of the fluoroquinolones have been well
      described. The bactericidal activity is maximised when the ratios of peak plasma
      drug concentration (Cmax): minimum inhibitory concentrations (MIC) or area under
      the concentration-time curve (AUC): MIC exceed specific threshold values.
      Knowledge of the pharmacodynamic relationships allows for appropriate drug
      selection and enables design of dosage regimens to maximise the bactericidal
      activity. Therapeutic drug monitoring of the fluoroquinolones may provide a means
      of optimising the dosage regimen in certain clinical situations (that is,
      meningitis and hospitalised pneumonias) with the goals of achieving a more
      predictable therapeutic response and minimising the potential for the development
      of resistance.

PMID- 11327198
TI  - Pharmacokinetics and pharmacodynamics of the triptan antimigraine agents: a
      comparative review.
AB  - The current approach to antimigraine therapy comprises potent serotonin 5-HT1B/1D
      receptor agonists collectively termed triptans. Sumatriptan was the first of
      these compounds to be developed, and offered improved efficacy and tolerability
      over ergot-derived compounds. The development of sumatriptan was quickly followed
      by a number of 'second generation' triptan compounds, characterised by improved
      pharmacokinetic properties and/or tolerability profiles. Triptans are believed to
      effect migraine relief by binding to serotonin (5-hydroxy-tryptamine) receptors
      in the brain, where they act to induce vasoconstriction of extracerebral blood
      vessels and also reduce neurogenic inflammation. Although the pharmacological
      mechanism of the triptans is similar, their pharmacokinetic properties are
      distinct. For example, bioavailability of oral formulations ranges between 14%
      (sumatriptan) and 74% (naratriptan), and their elimination half-life ranges from
      2 hours (sumatriptan and rizatriptan) to 25 hours (frovatriptan). Clearly, such
      diverse pharmacokinetic properties will influence the effectiveness of the
      compounds and favour the prescription of one over another in different patient
      populations. This article reviews the pharmacological properties of the triptans
      (time to peak plasma concentration, half-life, bioavailability and receptor
      binding) and relates these properties to efficacy and time of onset. It also
      considers the effects of concomitant medication, food, age and disease on the
      pharmacokinetics of the compounds. In addition, the relative merits, such as
      headache recurrence, tolerability and route of administration, are discussed.
      Finally, the performance of the triptans is considered in the context of direct
      head-to-head comparative trials that have assessed the efficacy profile of the
      compounds.

PMID- 11327199
TI  - Delavirdine: clinical pharmacokinetics and drug interactions.
AB  - Delavirdine, a non-nucleoside reverse transcriptase inhibitor (NNRTI), is a
      potent and specific inhibitor of HIV-1 reverse transcriptase. The approved
      therapeutic regimen for delavirdine is 400mg 3 times daily in combination with
      appropriate antiretroviral agents; however, a dose of 600mg twice daily appears
      to provide similar systemic exposure. The steady-state pharmacokinetics of
      delavirdine are not appreciably affected by food. Delavirdine undergoes extensive
      metabolism by cytochrome P450 (CYP) with little urinary excretion of unchanged
      drug. Metabolic drug interactions between delavirdine and nucleoside reverse
      transcriptase inhibitors are unlikely as their metabolic pathways differ;
      delavirdine has no effect on the pharmacokinetics of zidovudine. Concomitant use
      of CYP inducers, such as rifampicin (rifampin), rifabutin, phenytoin,
      phenobarbital or carbamazepine, should be avoided since delavirdine plasma
      concentrations are significantly lowered. Reduction in gastric acidity (pH > 3)
      decreases the extent of delavirdine absorption, so administration of antacids and
      the buffered formulations of didanosine should be separated from that of
      delavirdine by at least 1 hour. Delavirdine, unlike other currently available
      NNRTI agents, is an inhibitor rather than an inducer of CYP isozymes.
      Consequently, the drug interaction profile and rationale for combining
      delavirdine with other antiretroviral agents is unique among the current NNRTI
      agents. Delavirdine inhibits the CYP3A4-mediated metabolism of HIV protease
      inhibitors and thereby increases systemic exposure to protease inhibitors. The
      ability of delavirdine to enhance the pharmacokinetic profiles of protease
      inhibitors may permit the use of simplified administration regimens. Combining
      delavirdine and indinavir removes the food restrictions during indinavir
      administration. Furthermore, the superior virological response observed in
      antiretroviral regimens containing delavirdine and protease inhibitors has been
      attributed to the favourable pharmacokinetic interactions and the introduction of
      a new drug class in NNRTI-naive therapy-experienced patients. Pharmacokinetic
      drug interactions are an important consideration in selecting an HIV treatment
      regimen, due to the multiplicity of drugs that are coadministered and the varying
      direction and magnitude of interaction that can occur. Considerations for
      utilising delavirdine in a treatment regimen are different than for other NNRTI
      agents due to the unique drug interaction profile of delavirdine.

PMID- 11327200
TI  - Multiple dose pharmacokinetics of a new once daily extended release tolterodine
      formulation versus immediate release tolterodine.
AB  - OBJECTIVE: To determine the multiple dose pharmacokinetics of a new extended
      release (ER) capsule formulation of tolterodine, compared with the existing
      immediate release (IR) tablet, in healthy volunteers. DESIGN: Nonblind,
      randomised, 2-way crossover trial. PARTICIPANTS: 19 healthy volunteers (7
      females, 12 males), mean age 33 years (range 18 to 55 years). Prior to the study,
      all volunteers were classified as either extensive or poor metabolisers by
      cytochrome P450 2D6 genotyping. METHODS: Volunteers received tolterodine ER 4mg
      once daily or tolterodine IR 2mg twice daily for 6 days (all doses given as the L
      tartrate salt). A washout period of 7 days separated the 2 treatments. Serum
      concentrations of tolterodine, its active 5-hydroxymethyl metabolite (5-HM) and
      the active moiety (extensive metabolisers: sum of unbound tolterodine + 5-HM;
      poor metabolisers: unbound tolterodine) were measured for up to 48 hours post
      dose on day 6 (steady state). Tolerability was also determined. RESULTS: 17
      volunteers (13 extensive metabolisers, 4 poor metabolisers) completed the study
      and were evaluable for both treatment periods. The 90% confidence interval for
      the geometric mean ratio of area under the serum concentration-time curve to 24
      hours (AUC24) of the active moiety, for all volunteers combined, indicated
      equivalence for the 2 formulations. Pooled analysis also demonstrated that the
      peak serum concentration (Cmax) of the active moiety following administration of
      tolterodine ER was around 75% of that observed for the IR tablet, whereas the
      trough concentration was around 1.5-fold higher. Overall, the pharmacokinetics of
      tolterodine (irrespective of genotype) and 5-HM (extensive metabolisers only)
      were consistent with sustained drug release over 24 hours. Tolterodine ER was
      well tolerated. CONCLUSIONS: The new once daily ER formulation of tolterodine 4mg
      shows pharmacokinetic equivalence (AUC24) to the existing IR tablet given at a
      dose of 2mg twice daily. Findings of lower Cmax for tolterodine ER may explain
      the significantly lower rate of dry mouth subsequently observed in patients with
      overactive bladder.

PMID- 11327201
TI  - Reproduction in the Noughties: will the scientists have all the fun?
AB  - The past 20-30 years have seen major advances in our understanding of human
      reproduction and in our ability to manipulate it, as well as major social changes
      in human reproductive and sexual attitudes. Many of these advances and changes
      developed out of the first successful in vitro fertilisation (IVF) of the human
      oocyte. It is also the case that 30 years ago few foresaw what was to come, and
      many were at best doubtful and often were very critical of the scientific work
      which led to human IVF and to many of the subsequent developments. This lack of
      foresight provides us with a lesson about the dangers that we face in looking
      forward and attempting to predict the future. This review will try to convey, not
      comprehensively but through examples, the flavour of current activities in
      Assisted Reproduction clinics and research laboratories around the world and what
      is being talked about for the future in respect of emergent patient demands and
      anticipated clinical needs. This clinically driven approach will form the basis
      for consideration of some underlying scientific aspects of reproductive research,
      some of the ethicolegal issues that may arise, and the implications of this
      anticipated future for our current approaches to medical education. The future
      will be considered not simply in terms of the New Reproduction itself but also in
      its interaction with the opportunities and challenges presented by the New
      Genetics. It is perhaps in the interaction between these two fields of endeavour
      that some of the most difficult challenges ahead lie.

PMID- 11327202
TI  - The thymus of the hairless rhino-j (hr/rh-j) mice.
AB  - The hairless (hr) gene is expressed in a large number of tissues, primarily the
      skin, and a mutation in the hr gene is responsible for the typical cutaneous
      phenotype of hairless mice. Mutant hr mouse strains show immune defects involving
      especially T cells and macrophages, as well as an age-related immunodeficiency
      and an accelerated atrophy of the thymus. These data suggest that the hr mutation
      causes a defect of this organ, although hr transcripts have not been detected in
      fetal or adult mice thymus. The present study analyses the thymus of young (3 mo)
      and adult (9 mo) homozygous hr-rh-j mice (a strain of hairless mice) by means of
      structural techniques and immunohistochemistry to selectively identify thymic
      epithelial cells, dendritic cells, and macrophages. There were structural
      alterations in the thymus of both young and adult rh-rh-j mice, which were more
      severe in older animals. These alterations consisted of relative cortical
      atrophy, enlargement of blood vessels, proliferation of perivascular connective
      tissue, and the appearance of cysts. hr-rh-j mice also showed a decrease in the
      number of epithelial and dendritic cells, and macrophages. Taken together,
      present results strongly suggest degeneration and accelerated age-dependent
      regression of the thymus in hr-rh-j mice, which could explain at least in part
      the immune defects reported in hairless mouse strains.

PMID- 11327203
TI  - Evidence of neuroanatomical connection between the superior cervical ganglion and
      hypoglossal nerve in the hamster as revealed by tract-tracing and degeneration
      methods.
AB  - Previous studies have shown the existence of a sympathetic component in some
      cranial nerves including the hypoglossal nerve. In this study, the horseradish
      peroxidase (HRP) tract-tracing retrograde technique and experimental degeneration
      method were used to elucidate the possible neuroanatomical relationship between
      the superior cervical ganglion (SCG) and the hypoglossal nerve of hamsters. About
      10% of the SCG principal neurons were HRP positive following the tracer
      application to the trunk of hypoglossal nerve. Most of the HRP-labelled neurons
      were multipolar and were randomly distributed in the ganglion. When HRP was
      injected into the medial branch of the hypoglossal nerve, some of the SCG neurons
      were labelled, but they were not detected when HRP was injected into the lateral
      branch. The present findings suggest that postganglionic sympathetic fibres from
      the SCG may travel along the hypoglossal nerve trunk via its medial branch to
      terminate in visceral targets such as the intralingual glands. By electron
      microscopy, the HRP reaction product was localised in the neuronal somata and
      numerous unmyelinated fibres in the SCG. In addition, HRP-labelled axon profiles
      considered to be the collateral branches of the principal neurons contained
      numerous clear round and a few dense core vesicles. Besides the above, some HRP
      labelled small myelinated fibres, considered to be visceral afferents, were also
      present. Results of experimental degeneration following the severance of the
      hypoglossal nerve showed the presence of degenerating neuronal elements both in
      the hypoglossal nucleus and the SCG. This confirms that the hypoglossal nerve
      contains sympathetic component from the SCG which may be involved in regulation
      of the autonomic function of the tongue.

PMID- 11327204
TI  - The course of the buccal nerve: relationships with the temporalis muscle during
      the prenatal period.
AB  - The aim of this study was to describe the course of the buccal nerve and its
      relationships with the temporalis muscle during the prenatal period. Serial
      sections of 90 human fetal specimens ranging from 9 to 17 wk development were
      studied by light microscopy. Each fetal specimen was studied on both right and
      left sides, making a total of 180 cases for study. A 3-D reconstruction of the
      region analysed in one of the specimens was made. In 89 cases the buccal nerve
      was located medial to the temporalis muscle; in 73 cases it penetrated the
      muscle; in 15 cases it lay in a canal formed by the muscle fibres and was covered
      by fascia, and finally, in 3 cases it was a branch of the inferior alveolar
      nerve. The study has revealed that in a large number of cases the buccal nerve
      maintains an intimate association with the temporalis muscle.

PMID- 11327205
TI  - The orientation of the articular facets of the zygapophyseal joints at the
      cervical and upper thoracic region.
AB  - Knowledge of the orientation of facet joints in the cervical and upper thoracic
      region is important for understanding the biomechanical properties and clinical
      conditions relevant to the neck. The study was undertaken on dry macerated bones
      from 30 adult male human vertebral columns. The orientation of the superior
      articular facets in relation to their inclination with the sagittal and
      transverse planes was examined between C3 and T3 vertebrae in each column. The
      linear dimensions of the superior articular facets and the width/height ratio
      were also calculated. The results show that all vertebrae at C3 level and 73% at
      C4 level displayed posteromedially facing superior articular facets. Similarly at
      T1 level (C7/T1 joint) and below, all columns showed posterolaterally facing
      superior articular facets. The level of change in orientation, from posteromedial
      to posterolateral facing superior facets, was not constant and occurred anywhere
      between C4 (C3/C4 joint) and T1 (C7/T1 joint). The change in orientation followed
      2 different patterns, i.e. sudden or gradual. The C6 vertebra (C5/C6 joint) was
      the most frequent site to show the transition. The shape of the superior
      articular facets was circular to oval at C3, C4 and C5 levels and gradually
      changed to a transversely elongated surface at C7 and T1. These findings
      correlate well with various cervical movements and associated clinical
      conditions.

PMID- 11327207
TI  - An anatomical investigation of the human cervical facet capsule, quantifying
      muscle insertion area.
AB  - Facet capsule injury has been hypothesised as a mechanism for neck pain. While
      qualitative studies have demonstrated the proximity of neck muscles to the
      cervical facet capsule, the magnitude of their forces remains unknown owing to a
      lack of quantitative muscle geometry. In this study, histological techniques were
      employed to quantify muscle insertions on the human cervical facet capsule.
      Computerised image analysis of slides stained with Masson's trichrome was
      performed to characterise the geometry of the cervical facet capsule and
      determine the total insertion area of muscle fibres into the facet capsule for
      the C4-C5 and C5-C6 joints. Muscle insertions were found to cover 22.4+/-9.6% of
      the capsule area for these cervical levels, corresponding to a mean muscle
      insertion area of 47.6+/-21.8 mm2. The magnitude of loading to the cervical facet
      capsule due to eccentric muscle contraction is estimated to be as high as 51 N.
      When taken in conjunction with the forces acting on the capsular ligament due to
      vertebral motions, these forces can be as high as 66 N. In that regard, these
      anatomical data provide quantitative evidence of substantial muscle insertions
      into the cervical facet capsular ligament and provide a possible mechanism for
      injury to this ligament and the facet joint as a whole.

PMID- 11327206
TI  - NADPH-diaphorase activity and nitric oxide synthase isoforms in the trophoblast
      of Calomys callosus.
AB  - The pattern of expression of a variety of placental nitric oxide synthase
      isoforms has contributed to elucidating the regulatory mechanisms of nitric oxide
      (NO) synthesis during gestation. The maintenance of vascular tone, attenuation of
      vasoconstriction, prevention of platelet and leukocyte adhesion to the
      trophoblast surface, and possible participation in uterine blood flow seem to be
      the main functions of NO generated at the fetal-maternal interface in humans and
      mice. Extending this knowledge to other rodent species commonly used as
      laboratory animals, in this study we focus on NADPH-diaphorase activity and the
      distribution of nitric oxide synthase isoforms (NOS) in the trophoblast cells of
      Calomys callosus during different phases of pregnancy. NADPH-diaphorase activity
      was evaluated cytochemically and the presence of NOS isoforms detected by
      immunohistochemistry. These techniques were performed on pre- and
      postimplantation embryos in situ and in vitro, as well as in placentae on d 14
      and 18 of pregnancy. Neither NADPH-diaphorase activity nor inducible or
      endothelial NOS isoforms were found in pre-implanting embryos except after
      culturing for at least 48 h, when some of the embryonic cells were positive for
      the diaphorase reaction. On d 6.5 of pregnancy, trophoblast cells showed intense
      diaphorase activity both in situ and under in vitro conditions. A positive
      reaction was also found in the different placental trophoblast cells on d 14 and
      18 of pregnancy. The inducible NOS (iNOS) isoform, but not the endothelial
      isoform, was immunodetected in trophoblast cells from the placenta and from
      postimplantation embryos in situ and under in vitro conditions. These results
      strongly suggest the production of NO by the iNOS isoform in the trophoblast of
      Calomys callosus after embryo implantation. The data also emphasise a possible
      role for the trophoblast in producing and releasing cytotoxic molecules at the
      fetal-maternal interface.

PMID- 11327208
TI  - The afferent connections of the posterior hypothalamic nucleus in the rat using
      horseradish peroxidase.
AB  - The posterior hypothalamic nucleus has been implicated as an area controlling
      autonomic activity. The afferent input to the nucleus will provide evidence as to
      its role in autonomic function. In the present study, we aimed to identify the
      detailed anatomical projections to the posterior hypothalamic nucleus from
      cortical, subcortical and brainstem structures, using the horseradish peroxidase
      (HRP) retrograde axonal transport technique in the rat. Subsequent to the
      injection of HRP into the posterior hypothalamic nucleus, extensive cell
      labelling was observed bilaterally in various areas of the cerebral cortex
      including the cingulate, frontal, parietal and insular cortices. At subcortical
      levels, labelled cells were observed in the medial and lateral septal nuclei, the
      bed nucleus of stria terminalis, and various thalamic and amygdaloid nuclei. Also
      axons of the vertical and horizontal limbs of the diagonal band were labelled and
      labelled cells were localised at the CA1 and CA3 fields of the hippocampus and
      the dentate gyrus. The brainstem projections were from the medial, lateral and
      parasolitary nuclei, the intercalated nucleus of the medulla, the sensory nuclei
      of the trigeminal nerve, and various reticular, vestibular, raphe and central
      grey nuclei. The posterior hypothalamic nucleus also received projections from
      the lateral and medial cerebellar nuclei and from upper cervical spinal levels.
      The results are discussed in relation to the involvement of the posterior
      hypothalamic nucleus in autonomic function and allows a better understanding of
      how the brain controls visceral function.

PMID- 11327209
TI  - There is no loss of motor neurons in the rat spinal cord during postnatal
      maturation.
AB  - Motor neurons are lost during embryonic development, but it remains controversial
      whether motor neuron cell death occurs during postnatal life. In this study we
      investigated the effect of postnatal maturation on the number of intact spinal
      motor neurons in the rat using retrograde labelling with model-based counting,
      and an unbiased stereological counting technique. To determine the number of
      motor neurons innervating a specific forelimb muscle in rats of different
      postnatal ages FluoroGold was injected into the flexor carpi radialis. Before
      postnatal day 21 there were higher numbers of retrogradely labelled motor neurons
      than in adult rats, suggesting a 'loss' with postnatal maturation. This loss may
      be attributed to tracer diffusion to adjacent muscles and to the permeability of
      the muscle spindle capsule in younger animals. To obtain an unbiased estimate of
      the number of motor neurons in the C7 and C8 segments of the postnatal rat
      cervical spinal cord the fractionator/optical disector counting technique was
      used. This method did not show a loss of spinal motor neurons between birth and
      adulthood. The main conclusion from this study is that there is no loss of spinal
      motor neurons during postnatal maturation.

PMID- 11327211
TI  - Intrathymic lymph nodes in humans.
AB  - An unusual lymph node exists in the centre of the human thymus. This lymph node,
      which we call an intrathymic lymph node (ITLN), possesses some interesting
      morphological characteristics. In ontogeny, this node seems to appear at the
      latter half of fetal period. The function of the ITLN is still unknown, but it is
      assumed that it may play a different role in the immune system than other
      peripheral lymph nodes by its characteristics.

PMID- 11327210
TI  - Size of neocortical neurons in control subjects and in Alzheimer's disease.
AB  - The aim of the present study was to estimate mean neuronal volume and absolute
      size distributions of the neocortical neurons in brains from controls and AD
      patients using stereological methods based on unbiased principles to determine
      whether changes in absolute cell size are part of the neuropathological pattern
      of Alzheimer's disease. The neocortex of 8 patients with Alzheimer's disease
      (AD), mean age 81.1 (68-94) y was compared with 9 nondemented controls, mean age
      80.9 (65-101) y. The brains came from Johns Hopkins University Hospital (JHUH) in
      Baltimore, USA, the Netherlands Brain Bank (NBB), and from a large brain
      repository in Denmark. The rotator method was used to obtain an estimate of cell
      volumes providing absolute size distributions of the volume of both cell
      perikaryon and cell nuclei. The geometric mean volume of cell nuclei in
      neocortical neurons was 328 microm3 (interindividual CV = 0.15) in the Alzheimer
      group compared with 277 microm3 (interindividual CV = 0.17) in controls which was
      a statistically significant increase (P = 0.049). The perikaryal volume was 1117
      microm3 in the Alzheimer group compared with 999 microm3 in controls which was a
      nonsignificant difference (P = 0.20). There was a highly significant correlation
      between the nuclear and perikaryal volumes in all individuals. The average slope
      of the regression lines was significantly higher in the Alzheimer patients than
      in the controls, illustrating that nuclear hypertrophy was more pronounced in the
      largest neurons.

PMID- 11327212
TI  - Neutrophil migration in tonsils.
AB  - Recent studies have indicated the existence of an active cellular defence in the
      secretion on the tonsillar surface. This defence seems to consist partly of
      physiologically active neutrophils and is present in health and during disease.
      The present study was undertaken to examine the migration of these neutrophils to
      the secretion on the mucosal surface. Tonsils from 6 patients with acute
      tonsillitis and 5 patients with snoring problems were removed and sectioned.
      Sections were stained immunohistochemically against CD15 to visualise
      neutrophils. Other sections were stained with acridine orange to detect bacteria.
      Clusters of neutrophils were frequently seen in tonsils both from patients with
      acute tonsillitis and from snorers. They were observed to be accumulated within
      the tonsillar epithelial layer. Streaks of neutrophils could be observed running
      not only from vessels mainly near or within the epithelium to the epithelial
      surface, but also from vessels far from the epithelium through the
      extrafollicular areas to the epithelial surface. Bacteria were not present in the
      epithelium. We consider that the findings indicate an active physiological
      migration of neutrophils to the tonsillar surface.

PMID- 11327213
TI  - An unusual case of complete renal fusion giving rise to a 'cake' or 'lump'
      kidney.

PMID- 11327214
TI  - Thoracic stomach in a centenarian female cadaver.

PMID- 11327215
TI  - Facial vein terminating in the superficial temporal vein: a case report.

PMID- 11327216
TI  - The pharmacology and toxicology of atypical antipsychotic agents.
AB  - Recently, atypical antipsychotic agents have largely replaced traditional agents
      as first-line drugs for the treatment of schizophrenia. It is likely that
      atypical agents will soon account for the majority of poisonings from
      antipsychotic agents that present to health care facilities in the US. This
      article reviews the pharmacodynamics, pharmacokinetics, and toxicology of
      atypical antipsychotic drugs, chiefly clozapine, risperidone, olanzapine, and
      quetiapine. A descriptive summary of the human overdose experience with these
      agents is provided. Adverse effect and drug interaction data are reviewed. Based
      on the available pharmacodynamic, pharmacokinetic, and human overdose data,
      recommendations on management are provided.

PMID- 11327217
TI  - Methotrexate poisoning with acute hepatorenal dysfunction.
AB  - A 17-year-old girl receiving high-dose methotrexate for the treatment of
      osteosarcoma developed complications of acute renal failure and liver dysfunction
      with a coagulation disorder. The methotrexate concentrations were quickly reduced
      from 600 micromol/L to 50 micromol/L by treatment with plasma exchange and
      hemodialysis at 72 hours after discontinuation of the drug. After this reduction,
      continuous hemodiafiltration was initiated to further lower the methotrexate
      concentrations because of the persistently high and then the actual rebound in
      the plasma concentrations after plasma exchange and hemodialysis treatment.
      Continuous hemodiafiltration was able to reduce the concentrations without any
      rebound, despite its low column clearance. The rebound in plasma methotrexate
      concentrations seems to be corrected by plasma methotrexate after plasma exchange
      and/or hemodialysis.

PMID- 11327218
TI  - Life-threatening respiratory failure following accidental infusion of
      polyethylene glycol electrolyte solution into the lung.
AB  - Functional fecal retention is the most common cause of encopresis in children.
      Hospitalization may be required to clear the bowel following failure of
      outpatient management. Although the safety and efficacy of polyethylene glycol
      electrolyte solution is well established in children older than 6 months (1), its
      use should be carefully monitored in patients with altered mental status or
      impaired airway protective reflexes. We report the accidental infusion of
      NuLytely into the lungs of an 11-year-old female patient who consequently
      developed life-threatening acute lung injury. She rapidly developed respiratory
      failure requiring emergent tracheal intubation and suctioning, followed by
      mechanical ventilation. Careful monitoring is needed to avoid this potential
      complication if polyethylene glycol solution is infused via a nasogastric tube.

PMID- 11327219
TI  - Nosocomial poisoning associated with emergency department treatment of
      organophosphate toxicity--Georgia, 2000.
AB  - Emergency department (ED) staff caring for patients contaminated with toxic
      chemicals are at risk for developing toxicity from secondary contamination. This
      report describes three cases of occupational illnesses associated with
      organophosphate toxicity caused by exposure to a contaminated patient and
      underscores the importance of using personal protection equipment (PPE) and
      establishing and following decontamination procedures in EDs and other areas of
      acute care hospitals.

PMID- 11327220
TI  - Intentional overdose of dimercaptosuccinic acid in the course of treatment for
      arsenic poisoning.

PMID- 11327221
TI  - Flumazenil use in an emergency department: a survey.
AB  - OBJECTIVE: To evaluate the efficacy of flumazenil use by a one-year survey of
      practice in tan emergency department. DESIGN: During a one-year period, an
      observational prospective study in the emergency department of an urban community
      hospital enrolled every patient admitted with a history of pure or mixed
      benzodiazepine acute poisoning. Case records were secondarily reviewed by an
      expert group. Actual flumazenil use during hospitalization was compared to
      currently recommended indications. In order to evaluate the efficacy of
      flumazenil use, patients who received flumazenil were matched with those who did
      not and effects on mortality, morbidity, number of costly procedures (CT scan,
      diagnostic toxicology, etc.) and duration of hospital stay were determined.
      RESULTS: Of the 1529 patients admitted in 1 year for acute poisoning, 478
      reportedly ingested at least one benzodiazepine. Twenty-nine patients (6%)
      received flumazenil in the emergency department whereas the expert reviewers
      recommended flumazenil use in only 18 (3.7%). In 11/29 (38%) cases, the use of
      fumazenil was considered inappropriate. The expert group considered flumazenil to
      be contraindicated in 93 of 478 patients. Nonetheless, flumazenil was used in 11
      patients (rate of potentially harmful flumazenil use: 11/93; 12%), and a severe
      complication occurred in one of these patients after flumazenil. No significant
      difference could be shown in outcome, complication rate, number of complex
      procedures or duration of hospital stay between patients who received flumazenil
      and matched patients who did not. CONCLUSION: The use of flumazenil in the
      clinical practice of an emergency department fails to show any beneficial effect
      in adult patients. Moreover, contraindications are frequently overlooked and this
      may expose patients to substantial risk of complications.

PMID- 11327222
TI  - Poisoning at sea: injuries caused by chemicals aboard Danish merchant ships 1988
      1996.
AB  - INTRODUCTION: Injuries involving chemicals occur aboard merchant ships, since
      such agents are carried commonly on board either as cargo or as needed for
      running the ship. In case of events involving chemicals, the crew may seek advice
      from the Medical First Aid Guide for Use in Accidents Involving Dangerous Goods
      published by the International Maritime Organization. The Guide is currently
      under revision. To improve knowledge of what is relevant in such a guide, a study
      was undertaken to identify all intoxications and corrosive incidents occurring
      aboard Danish merchant ships. METHODS: A retrospective study of all intoxications
      and corrosive incidents reported to the Danish Maritime authorities between 1988
      and 1996. RESULTS: A total of 177 injuries were identified, of which 66 were
      systemic poisonings and 111 were due to corrosive damage to the eyes and skin.
      Thirteen of 66 systemic poisonings were fatal and almost three out of four
      corrosive injuries involved the eyes. CONCLUSIONS: This study and others show
      that the majority of injuries aboard merchant ships involving dangerous goods are
      amenable to first aid and symptomatic measures. Specific antidotes seem to have a
      limited role aboard merchant ships.

PMID- 11327223
TI  - Paraoxon sensitive phenylvalerate hydrolase in assessing the severity of acute
      paraoxon poisoning.
AB  - INTRODUCTION: Intoxications with organophosphorous compounds, especially
      paraoxon, are frequent. Organophosphorous compounds inhibit serine hydrolases
      such as acetylcholine, butyrilcholine, and carboxyl esterases although
      acetylcholine and butyrylcholine are too sensitive to paraoxon to be useful
      markers of severity. They cannot show a dose-dependent inhibition during an acute
      organophosphorous compounds exposure because maximal enzyme inhibition is reached
      at very low organophosphorous compounds concentrations. PURPOSE: To determine in
      vitro the dose-effect relationship between the activity of the paraoxon-sensitive
      phenylvalerate hydrolase, a member of the carboxvl esterases family, and the
      paraoxon dose, and to assess its utility as a putatively less sensitive enzyme
      marker to monitor the severity of an acute paraoxon intoxication. MATERIALS AND
      METHODS: Phenylvalerate hydrolase and butyrylcholine activities were determined
      in serum of nine healthy human volunteers before and after addition of different
      concentrations of paraoxon. The determination of phenyl-valerate hydrolase
      activity was carried out using a modification of the method described by Johnson.
      A commercially available kit was used to measure butyrylcholine activity.
      RESULTS: Paraoxon inhibits phenyl-valerate hydrolase activity at concentrations
      above 10 M. Maximal inhibition (approximately 50% of baseline) is achieved at
      concentrations above 2.5 x 10(-7) M. The IC50 value of paraoxon for phenyl
      valerate hydrolase is 34+/-2 nM. The uninhibited phenyl-valerate hydrolase
      activity is due to paraoxon-resistent isoforms. Paraoxon begins inhibiting
      butyrylcholine activity at concentrations above 10(-9) M. At concentrations above
      5 x 10(-5) M, no butyrylcholine activity is measulrable. The IC50 value of
      paraoxon for butyrylcholine is 150+/-23 nM. CONCLUSION: The paraoxon-sensitive
      subunit of phenyl-valerate hydrolase shows dose-dependent inhibition when exposed
      to paraoxon in vitro, but it is even more sensitive than butyrylcholine to
      paraoxon inhibition. Determinations of phenyl-valerate hydrolase activity to
      assess the severity of an acute organophosphorous compounds poisoning cannot be
      recommended, but phenyl-valerate hydrolase may have utility in worker
      surveillance.

PMID- 11327224
TI  - Do not get complacent about carbon monoxide poisoning.

PMID- 11327225
TI  - Carbon monoxide cardiotoxicity.
AB  - Cardiac dysfunction including arrhythmias and myocardial ischemia have often been
      reported in carbon monoxide poisoning; scattered punctiform hemorrhages
      throughout the heart have been documented in autopsy samples. An appropriate
      diagnostic approach is crucial to assess carbon monoxide cardiac damage. This
      evaluation may be confounded by several factors, including the absence of overt
      symptoms and of specific ischemic changes in the electrocardiogram. In
      experimental studies, laboratory animals can develop cardiac changes similar to
      those seen in humans and therefore proved to be useful models to study the
      effects and the mechanisms of cardiac damage due to carbon monoxide. These
      investigations, as well as others performed in vitro, provide support for a
      direct action of carbon monoxide on the heart, in addition to systemic hypoxia
      produced by carboxyhemoglobin formation. This review focuses on the diagnostic
      aspects of carbon monoxide cardiotoxicity. Experimental results obtained in
      animals and in vitro models are also discussed.

PMID- 11327226
TI  - Cardiac damage in pediatric carbon monoxide poisoning.
AB  - BACKGROUND: Cardiovascular disorders including myocardial ischemia and heart
      failure have been described in both laboratory animals and humans following
      carbon monoxide poisoning. Carbon monoxide cardiotoxicity may be clinically
      occult and often remains undiagnosed because of the lack of overt symptoms and
      specific ischemic changes in the electrocardiogram. Routine myocardial necrosis
      markers have low diagnostic efficiency, particularly in patients with concomitant
      skeletal muscle necrosis or multiple organ failure complicating carbon monoxide
      poisoning. Carbon monoxide-induced cardiotoxicity has been investigated rarely in
      children. CASE REPORT: This paper describes carbon monoxide poisoning in a 12
      year-old child who suffered from occult cardiac damage despite mild symptoms and
      low carboxy hemoglobin concentrations. Myocardial and mitral valve dysfunctions
      were observed, suggesting an ischemia-like syndrome. Cardiac damage was
      completely reversible within 1 month. CONCLUSION: This case report supports that
      a prolonged carbon monoxide exposure can cause cardiac damage in children even in
      the absence of specific symptoms, cerebral failure and high carboxyhemoglobin
      concentrations.

PMID- 11327227
TI  - Epidemiology of acute carbon monoxide poisoning in a Spanish region.
AB  - BACKGROUND: In Spain, as in most of the world, the incidence of acute carbon
      monoxide poisoning is probably underestimated. METHODS: During an eighteen-month
      period we studied, by means of a standardized data collection form, all the cases
      of acute carbon monoxide poisoning that were diagnosed in 2 university hospitals.
      RESULTS: During the study, 154 patients were diagnosed with carbon monoxide
      poisoning. The mean age was 32.2+/-15.5 years. The two principal exposure sites
      were the kitchen (43%) and bathroom (23%). The majority of the cases related to
      malfunction of the water heater (30%) and of the central heating (23%) and 68%
      occurred in the home. Improper combustion of butane (31%), propane (13%), and
      natural gas (12%) were most frequent. The most prevalent clinical manifestations
      were headache (94%), dizziness (56%), nausea (45%), loss of consciousness (38%),
      and weakness (34%). Five patients died. In 14.4%, symptoms suggested delayed
      neurological syndrome. The largest number of cases of poisoning occurred during
      the months of December and January. CONCLUSIONS: Compared with previous Spanish
      series or with the antecedent year, acute carbon monoxide poisoning has a high
      prevalence in our region. Two factors appear to be essential to the accurate
      diagnosis of acute carbon monoxide poisoning: 1) the ability of emergency room
      physicians to recognize the clinical symptoms of carbon monoxide poisoning and 2)
      access to a carbon monoxide-oximeter.

PMID- 11327228
TI  - Treatment of methanol and isopropanol poisoning with intravenous fomepizole.
AB  - CASE REPORT: We report a case of mixed methanol and isopropanol poisoning in a
      patient who refused dialysis but agreed to treatment with intravenous fomepizole.
      The patient was asymptomatic on arrival, with initial blood methanol and
      isopropanol concentrations of 146 mg/dL and 39 mg/dL, respectively. Blood ethanol
      was undetectable. The patient was treated with fomepizole twice daily
      intravenously until blood methanol was undetectable. No side effects of therapy,
      other than transient eosinophilia, were observed. The evolution was uneventful
      and no metabolites of either alcohol were detected at any time during the
      hospitalization. The decay of plasma methanol and isopropanol under fomepizole
      treatment were well described by first-order kinetics. The plasma elimination
      half-lives of methanol and isopropanol were 47.6 hours and 27.7 hours,
      respectively. Fomepizole appears to have been effective in blocking the toxic
      metabolism of both methanol and isopropanol and was associated with a favorable
      outcome.

PMID- 11327229
TI  - Death due to inhalation of industrial acetylene.
AB  - CASE REPORT: Acetylene is a commonly found industrial agent that, when mixed with
      oxygen, is used for welding. This report outlines circumstances surrounding the
      death of a 40-year-old male with presumptive evidence of abuse of the substance
      and subsequent death. The article covers the uses of acetylene, the toxic effects
      attributed to the gas, and the circumstances of the incident.

PMID- 11327230
TI  - Determination of urinary hippuric acid in toluene abuse.
AB  - BACKGROUND: Volatile substance abuse is practiced mainly by adolescents and young
      adults. Its effects are central nervous system excitation followed by central
      nervous system depression, at times accompanied by seizures. It may cause sudden
      death as a result of ventricular arrhythmias, reflex vagal inhibition,
      respiratory depression, and anoxia. Chronic toxicity may involve the nervous
      system, heart, kidney, and liver. Toluene-based adhesives are among the most
      commonly inhaled substances. CASE REPORT: A 14-year-old female presented with
      confusion, hallucinations, and intermittent laughing and crying after having
      inhaled contact glue several times daily in the course of 5 days. Her condition
      improved within 3 h. Urinary hippuric acid was 93.9 g/g creatinine indicating
      heavy toluene exposure (biological exposure index, BEI, is 1.6 g/g creatinine).
      CONCLUSION: In this patient, urinary hippuric acid was a biomarker for her
      toluene abuse.

PMID- 11327231
TI  - Intravenous chlorhexidine gluconate causing acute respiratory distress syndrome.
AB  - CASE REPORT: A 67-year-old man undergoing a colectomy for colon cancer was
      unintentionally administered 0.8 mg of chlorhexidine gluconate intravenously and
      subsequently developed acute respiratory distress syndrome. The operation was
      discontinued immediately. Respiratory failure progressed despite three cycles of
      plasma exchange beginning on day 1. Extracorporeal membrane oxygenation for 72 h
      beginning on day 3 was associated with dramatic improvement. The patient showed
      complete recovery of intellectual function and subsequently underwent a colectomy
      with lymph node dissection for colon cancer. CONCLUSION: For acute respiratory
      distress syndrome secondary to chlorhexidine gluconate intoxication,
      consideration should be given to the treatment of initial respiratory distress
      and subsequent pneumonia. The benefit of extracorporeal membrane oxygenation and
      plasma exchange may merit further investigation.

PMID- 11327233
TI  - Use of anthrax vaccine in the United States: recommendations of the Advisory
      Committee on Immunization Practices.
AB  - These recommendations concern the use of aluminum hydroxide adsorbed cell-free
      anthrax vaccine (Anthrax Vaccine Adsorbed [AVA], BioPort Corporation, Lansing,
      MI) in the United States for protection against disease caused by Bacillus
      anthracis. In addition, information is included regarding the use of
      chemoprophylaxis against B. anthracis.

PMID- 11327232
TI  - Delayed life-threatening reaction to anthrax vaccine.
AB  - BACKGROUND: Anthrax is an acute infectious disease caused by the spore-forming
      bacterium Bacillus anthracis. Due to the current world threat of unpredictable
      biological terrorism, the Department of Defense has mandated the systematic
      vaccination of all US military personnel against this warfare agent. Many may
      experience al mild flu-like illness and soreness at the injection site, but
      systemic reactions are rare. CASE REPORT: We report a delayed and potentially
      serious life-threatening adverse reaction to anthrax vaccine. A previously
      healthy 34-year-old male was transported to the emergency department with
      dyspnea, diaphoresis, pallor, and urticarial wheals on his face, arms, and torso
      after the administration of the third dose of anthrax vaccine. All symptoms
      resolved after pharmacological intervention and the patient was discharged.
      Pharmaco-epidemiological data indicate that 30% of anthrax vaccine recipients
      experience mild local reactions. With large numbers of military personnel being
      vaccinated, emergency physicians may encounter more vaccine-related adverse
      reactions.

PMID- 11327234
TI  - Osteoprotegerin, RANK, and RANK ligand: the good, the bad, and the ugly in
      rheumatoid arthritis.

PMID- 11327236
TI  - Rheumatoid arthritis: beyond the lymphocyte.

PMID- 11327235
TI  - Treatment related mortality versus quality of life--a balancing act.

PMID- 11327237
TI  - The clinical significance of IgA antiphospholipid antibodies.

PMID- 11327238
TI  - Expression of interleukin 10 mRNA and protein by synovial fibroblastoid cells.
AB  - OBJECTIVE: To determine if fibroblast-like synoviocytes (FLS) express interleukin
      10 (IL-10) mRNA and protein and functional IL-10 receptors. METHODS: The pattern
      of IL-10 production was analyzed in inflammatory synovial tissues by
      immunohistochemistry. Expression of IL-10 mRNA and protein was determined by
      Northern blot analysis and ELISA in resting FLS and following stimulation with IL
      1beta and tumor necrosis factor-alpha (TNF-alpha). IL-10 receptor expression was
      measured on cultured FLS by immunohistochemistry and FACS analysis after
      treatment with biotinylated IL-10. Responsiveness of FLS to IL-10 was determined
      by multigene assay and inhibition of prostaglandin E2 induced morphologic
      changes. Bioactivity was confirmed by downregulation of interferon-gamma
      stimulated HLA-DR expression by FACS and inhibition of TNF-alpha production by
      U937 cells. RESULTS: Using immunohistochemistry, we detected IL-10 in the lining
      layer of inflamed synovial tissue and FLS. ELISA on unstimulated third passage
      FLS culture supernatants revealed IL-10 production that varied over time and
      among cell lines. FLS produced IL-10 mRNA constitutively. IL-10 production was
      upregulated by IL-1beta and TNF-alpha. IL-10 bound to receptors on FLS and
      induced functional changes. Endogenously released FLS IL-10 was biologically
      active. CONCLUSION: Mesenchymal lining cells in the inflamed joint produce IL-10.
      In addition, cultured FLS constitutively produce IL-10 mRNA and protein that is
      bioactive and can be upregulated by IL-1beta and TNF-alpha. FLS express
      functional IL-10 receptors. These results suggest that IL-10 released by
      mesenchymal cells in inflammatory arthritis can modulate synovial inflammation
      and joint destruction by paracrine and/or autocrine mechanisms.

PMID- 11327239
TI  - Arthritis and rheumatism are neglected health priorities: a bibliometric study.
AB  - OBJECTIVE: To investigate the frequency of publications about arthritis and
      rheumatic diseases relative to other diseases and to examine which topics
      received most attention. METHODS: Available health statistics were used to
      quantify the burden of illness due to musculoskeletal (MSK) conditions. Next, a
      bibliographic analysis of MEDLINE was performed comparing disease categories
      using the MeSH tree structure for 1991 and 1996. Diseases were ranked according
      to the frequency of citations attributable to them and further analyses were
      performed for journal categories, MeSH subheadings, and the frequency of
      citations for specific types of arthritis and rheumatic diseases. RESULTS:
      Compared with 9 other causes, MSK diseases are leading contributors to health
      professional consultations, total health costs, chronic ill health, and
      disability. In contrast, MSK diseases ranked ninth among twelve major MEDLINE
      disease categories in 1996 and 1991. These rankings were similarly low across
      journal categories reflecting basic science research and clinical application.
      Radiography, rehabilitation, history and embryology were the most frequently used
      subheadings for MSK diseases. In 1996, there were 16,603 citations for MSK
      diseases, led by bone diseases (7,304 citations), joint diseases (4,987),
      muscular diseases (4,236), arthritis (3,555), and rheumatic diseases (3195).
      Among arthritic and rheumatic diseases, rheumatoid arthritis had the largest
      number of citations (2,004), followed by systemic lupus erythematosus (927) and
      osteoarthritis (793). CONCLUSION: Arthritis and rheumatic diseases receive far
      less attention in the scientific literature than is warranted by their enormous
      and growing disease burden. Both research and dissemination are lacking and more
      adequate resources for these activities are indicated.

PMID- 11327240
TI  - Modulation of TIMP-1 synthesis by antiinflammatory cytokines and prostaglandin E2
      in interleukin 17 stimulated human monocytes/macrophages.
AB  - OBJECTIVE: To examine the regulation of tissue inhibitor of metalloproteinase 1
      (TIMP-1) synthesis by interleukin 17 (IL-17) stimulated human
      monocytes/macrophages in primary culture in the presence of prostaglandin E2
      (PGE2) and antiinflammatory cytokines, and to compare this with the regulation of
      matrix metalloproteinase (MMP-9) production. METHODS: IL-17 stimulated human
      monocytes isolated from the peripheral blood of healthy donors were cultured in
      the presence of PGE2, cyclic adenosine monophosphate (cAMP) mimetics (IBMX, cAMP,
      forskolin, cholera toxin), or antiinflammatory cytokines (IL-4, IL-10, IL-13), or
      with protein kinase inhibitors of diverse specificity. MMP-9 and TIMP-1 were
      measured using specific ELISA, while expression of specific messenger RNA was
      determined by Northern blotting. RESULTS: IL-17 stimulated an increased level of
      MMP-9 production relative to TIMP-1 production in monocytes/macrophages.
      Stimulation was accompanied by upregulation of specific MMP-9 mRNA expression
      relative to TIMP-1 mRNA. Exogenous PGE2, cAMP, and cAMP-mimetics completely
      inhibited both basal and IL-17 induced MMP-9 synthesis, while only IL-17 induced
      TIMP-1 synthesis was abrogated. The same effect was found for the
      antiinflammatory cytokines. Both basal and IL-17 induced production of TIMP-1
      involved p42/44 and p38 kinases and nuclear factor kappaB signaling pathways.
      CONCLUSION: The excess of MMP-9 over TIMP-1 production, and decreased inhibition
      of MMP-9 activity in chronic rheumatoid diseases, may result in cartilage
      degradation and joint destruction.

PMID- 11327241
TI  - High dose chemotherapy followed by autologous peripheral blood stem cell
      transplantation or conventional pharmacological treatment for refractory
      rheumatoid arthritis? A Markov decision analysis.
AB  - OBJECTIVE: To evaluate the effect of high dose chemotherapy (HDC) followed by
      autologous hematopoietic stem cell transplantation (ASCT) in comparison to
      conventional pharmacological therapy in the treatment of patients with
      refractory, progressively erosive rheumatoid arthritis (RA). METHODS: Decision
      analysis using a Markov model with a 5.5 year time horizon. Probabilities of
      transition towards 5 different health states, ranging from 70% improvement to
      death, were derived from published case reports, patient series, and expert
      panels. Quality of life (QOL) estimates were obtained from 2 RA clinical trials.
      Patients were hypothetical cohorts of 50-year-old female patients with
      progressively erosive, active RA, who failed treatment with methotrexate,
      combination therapy, and tumor necrosis factor blocking agents. Interventions
      were HDC + ASCT versus conventional pharmacological treatment with a
      (combination) therapy of disease modifying antirheumatic drugs. As main outcome
      measures, we included the number of quality adjusted life years (QALY) after HDC
      + ASCT compared to conventional therapy. Sensitivity analysis was performed to
      investigate the influence of treatment related mortality (TRM) and the influence
      of QOL during HDC + ASCT, and to assess the minimal desired effectiveness of HDC
      + ASCT for a given TRM of 1% and 10%. RESULTS: HDC + ASCT and conventional
      pharmacological treatment were equally effective in the base-case analysis (3.48
      vs 3.46 QALY). A TRM of less than 3.3% favored HDC + ASCT as the preferred
      treatment. The analysis showed that when TRM was set at 1%, a relatively short
      period of efficacy was sufficient to remain the preferred strategy, whereas a TRM
      of 10% would require a sustained response for several years. CONCLUSION: This
      model predicted equally favorable effects of HDC + ASCT and conventional therapy
      in the treatment of refractory RA in the base-case. The minor differences in
      terms of QALY seem to indicate that clinical decision making should be guided by
      patient preferences. However, better clinical efficacy might be achieved by
      adaptation of the treatment regimen of HDC + ASCT and patient selection. The
      model supports the need for randomized clinical trials and may contribute to an
      optimal study design.

PMID- 11327242
TI  - Low mannose binding lectin predicts poor prognosis in patients with early
      rheumatoid arthritis. A prospective study.
AB  - OBJECTIVE: To determine whether low mannose binding lectin (MBL) is associated
      with poor prognosis in rheumatoid arthritis (RA) and whether patients with RA
      have increased frequency of MBL deficiency. METHODS: Patients with recent onset
      symmetric polyarthritis (< 1 year, median 3 mo) were recruited if they had not
      been treated longer than 2 weeks with disease modifying drugs. They were
      reevaluated after 6 months and their disease activity and progression were
      correlated with their MBL concentration, rheumatoid factor (RF) isotypes, and C
      reactive protein (CRP). Sixty-three female patients with advanced RA were also
      analyzed. RESULTS: Sixty-five patients with early arthritis fulfilled American
      College of Rheumatology criteria for RA and 52 were followed for 6 months or
      longer. Low MBL was associated with raised RF, IgA RF in particular (p = 0.02).
      and also with a combined elevation of IgM and IgA RF (p = 0.035). Patients with
      low MBL (lowest 25th percentile) showed less improvement after 6 months of
      treatment than patients in the highest MBL quartile. This applied to the Thompson
      joint score (p = 0.03) and grip strength (p = 0.004). Low MBL was also
      significantly associated with radiological joint erosions at recruitment and at 6
      month followup (p = 0.039); and the group with advanced RA also showed a
      significant association between low MBL concentration and radiological damage (p
      = 0.036). However. neither patient group had increased frequency of MBL
      deficiency compared to healthy controls. CONCLUSION: Low MBL predicts poor
      prognosis in patients with early RA.

PMID- 11327243
TI  - Immunogenetic markers and seropositivity predict radiological progression in
      early rheumatoid arthritis independent of disease activity.
AB  - OBJECTIVE: A prospective clinical study of patients with recent onset rheumatoid
      arthritis (RA) to examine the relationship between inflammatory disease activity
      and joint destruction in a 4 year followup, and to evaluate prognostic markers
      for severe joint erosions early in the disease. METHODS: Eighty-seven patients
      with RA according to the American College of Rheumatology criteria and a disease
      duration < 2 years were followed for an observation time of 2 to 4 years (mean
      3.1 yrs). Variables of clinical and laboratory disease activity were monitored,
      and HLA-DRB1 alleles were determined. Hand and foot radiographs were taken every
      6 months. RESULTS: Multivariate analysis of independent contributions of
      covariates to progression of joint destruction resulted in a mixed effect
      regression model with significant influences for the presence of a shared epitope
      (SE) positive DR4 allele (SE+ DR4+; p = 0.007), rheumatoid factor (RF) IgA (p =
      0.01), and sex (p = 0.059), but not for clinical variables or acute phase
      reactants. The odds ratio to reach a Larsen score above 32 during the observation
      period of 4 years was increased in patients positive for RF IgM (OR 2.7, p =
      0.019), for the shared epitope on a DR4 allele (OR 8.6, p < 0.005), and in
      patients with erosions already at study entry (OR 11.9, p = 0.001). The highest
      sensitivity and specificity for the prediction of severe bone destruction (84%
      and 79%) were found when the presence of either a SE+ DR4 allele or of early
      erosions was used as a prognostic marker (OR 20.4, p < 0.0001). CONCLUSION: Our
      results show the pace of joint destruction in RA to be influenced by the presence
      of SE+ DR4 alleles, RF production, and sex and by the presence of erosive disease
      at presentation. Those prognostic markers exert their influence independently
      from the inflammatory disease activity.

PMID- 11327244
TI  - The value of a continuous ambulatory activity monitor to quantify the amount and
      intensity of daily activity in patients with rheumatoid arthritis.
AB  - OBJECTIVE: To examine the reliability, validity, and responsiveness of a
      continuous ambulatory activity monitor in patients with rheumatoid arthritis
      (RA). METHODS: Forty-one patients with RA, participating in a randomized
      controlled trial examining the effect of an intensive exercise program, were
      assessed by means of the Dynaport ADL (activities of daily living) monitor (AM).
      The time spent on activities (locomotion, standing, and active sitting) during 24
      hours and the intensity of trunk movement during these activities were recorded.
      To determine test-retest reliability 20 patients were reassessed with the AM one
      week after the first assessment. Construct validity of the AM was determined by
      comparing the AM results with physical fitness measures (muscle strength,
      endurance, joint mobility), disease activity, and functional status. As well, 37
      patients were assessed 18 months after the first assessment to determine
      responsiveness. RESULTS: All AM measurements showed satisfactory test-retest
      reliability (ICC 0.63-0.76). AM measures were significantly associated with
      physical fitness, functional status, and disease activity, indicating construct
      validity of the AM. The AM could discriminate between patients with improvement
      and deterioration in physical fitness, indicating sufficient responsiveness of AM
      variables. CONCLUSION: This study shows the value of an ambulatory activity
      monitor to quantify both the amount and intensity of physical activity of
      patients with RA during a day in their own environment. The ambulatory activity
      monitor seems to be a promising instrument for research into rehabilitation of
      patients with RA.

PMID- 11327245
TI  - The antiquity of rheumatoid arthritis: a reappraisal.
AB  - OBJECTIVE: To demonstrate the existence of rheumatoid arthritis (RA) before the
      19th century. METHODS: Survey of primary and secondary references on the history
      of rheumatic diseases. RESULTS: Paleopathological evidence suggests the existence
      of RA in America since 8000 BC and in Europe since the 7th century. Descriptions
      and representations of a symmetric chronic polyarthritis producing characteristic
      deformities can be found in Rome since 100 BC and India since 500 BC. The first
      clinical distinction between RA and gout was published in Mexico in 1578.
      Different historical conditions contributed to lack of recognition of RA by
      official medicine before 1800. The recognition of RA as a distinct entity in the
      19th century was influenced by socioeconomic circumstances. CONCLUSION: RA is not
      a recent disease. Historical investigation can provide useful clues on its
      pathogeny.

PMID- 11327246
TI  - Familial systemic lupus erythematosus in Finland.
AB  - OBJECTIVE: To perform a cross sectional nation-wide clinical study of familial
      systemic lupus erythematosus (SLE) in Finland. METHODS: We sought to identify all
      Finnish families in which at least 2 members satisfied the classification
      criteria for SLE. About 1,200 patients with SLE (80-85% of all patients attending
      Finnish hospitals) were contacted. Personal and/or phone interviews and
      examination of medical records were used to verify the diagnoses. A comparison of
      clinical characteristics was made between familial cases of SLE and matched
      sporadic controls. RESULTS: We identified 53 multiplex families with 113 SLE
      patients. Forty-six families had 2 affected members and 7 families had 3 affected
      members. There were 3 pairs of monozygotic female twins and one pair of dizygotic
      twins of the opposite sex concordant for SLE. Eleven (9.7%) of the 113 familial
      cases of SLE were male. No differences were found in the clinical presentation of
      SLE between familial and sporadic cases (sex, age at onset, major clinical
      manifestations, and common laboratory tests). The incidence of familial SLE was
      approximately 4-5%. CONCLUSION: Our study shows that familial and sporadic SLE
      are not different disease entities; this means that we can extrapolate the
      results of future genetic analyses in multiplex SLE families to all patients with
      SLE.

PMID- 11327247
TI  - Predictive factors for symptomatic osteonecrosis in patients with systemic lupus
      erythematosus.
AB  - OBJECTIVE: To analyze predictive factors for the development of osteonecrosis
      (ON) in a large cohort of patients with systemic lupus erythematosus (SLE)
      followed in a single center. METHODS: A nested matched case control design was
      used. Patients with SLE who developed ON during followup were identified from the
      University of Toronto Lupus Clinic database. The diagnosis of ON was confirmed by
      either radiographs, bone scans, tomograms, or magnetic resonance imaging. A
      comparison group of patients with SLE without ON was selected from the same
      database, matched by year of birth. sex, and year of entry to the clinic to the
      patients with ON. Clinical, laboratory, and therapeutic factors thought to be
      relevant to the development of ON were compared between the 2 groups. RESULTS:
      Seventy patients with SLE developed ON in the course of followup at the clinic.
      In univariate analysis, arthritis was the only clinical feature predictive of the
      development of ON. Use of glucocorticosteroid therapy, dose and duration, as well
      as Cushingoid appearance and cytotoxic therapy were also predictive for the
      development of ON. Multivariate analysis revealed that glucocorticosteroid use,
      the presence of arthritis, and the use of cytotoxic medications remained
      significant. CONCLUSION: Glucocorticosteroid therapy, the presence of arthritis,
      and use of cytotoxic medication are independent risk factors for development of
      ON in patients with SLE.

PMID- 11327248
TI  - Neuropsychiatric manifestations and their clinical associations in southern
      Chinese patients with systemic lupus erythematosus.
AB  - OBJECTIVE: To study the neuropsychiatric (NP) manifestations in a large cohort of
      southern Chinese patients with systemic lupus erythematosus (SLE) according to
      the new 1999 American College of Rheumatology (ACR) case definitions and their
      clinical associations. METHOD: Patients with SLE who were followed from 1984 to
      2000 were retrospectively reviewed. Patients with NP manifestations were
      ascertained and classified by at least 2 rheumatologists, with the collaboration
      of neurologists and psychiatrists. The association of NP manifestations with
      other clinical features and autoantibodies was studied by statistical analysis.
      RESULTS: Five hundred eighteen patients with SLE were studied. The female to male
      ratio was 7.8 to 1 and the mean age of disease onset was 29.5 +/- 12.0 years
      (range 9-80). The mean duration of followup was 7.3 +/- 6.7 years (range 0.3
      23.0). Ninety-six patients (19%) had 133 NP events and the mean number of events
      per patient-year of followup was 0.035. In decreasing order of frequency. these
      events were: seizure disorder (28%), cerebrovascular disease (19%), acute
      confusional state (14%), psychosis (11%), myelopathy (8%), mood disorder (6%),
      headache (4%), movement disorder (2%), cranial neuropathy (3%), demyelinating
      syndrome (1.5%), anxiety disorder (1.5%), mononeuritis multiplex/mononeuropathy
      (1.5%), aseptic meningitis (1%), and polyneuropathy (1%). Cognitive dysfunction
      was not classified because of the lack of standard neuropsychological testing for
      every patient. Univariate analysis revealed that NP-SLE was associated with a
      positive lupus anticoagulant (LAC) (p = 0.001), a strongly positive IgG
      anticardiolipin (aCL) (p = 0.01). leukopenia (p = 0.01), lymphopenia (p = 0.03),
      thrombocytopenia (p = 0.03), and pulmonary involvement (p = 0.03). Multivariate
      analysis showed that a strongly positive IgG aCL [RR 3.1 (1.3-7.7), p = 0.01] and
      a history of cyclophosphamide treatment [RR 4.3 (2.1-9.0), p < 0.001] were
      independently associated with NP manifestations in our cohort. Among the NP
      features, cerebrovascular disorder was particularly associated with the presence
      of LAC [OR 3.3 (1.4-8.0), p = 0.01] and a strongly positive IgG aCL [OR 3.1 (1.1
      8.2), p = 0.031]. CONCLUSION: The point prevalence of overt NP manifestations in
      our cohort of patients with SLE was 19%. This percentage was likely higher if
      subtle cognitive dysfunction was included. Seizure and cerebrovascular disorders
      were the most common NP features. The presence of antiphospholipid antibodies was
      significantly associated with NP manifestations, especially cerebrovascular
      disorders.

PMID- 11327249
TI  - Somatic and psychological features of headache in systemic lupus erythematosus.
AB  - OBJECTIVE: Headaches--especially of migrainous type--have been considered part of
      the disease spectrum of systemic lupus erythematosus (SLE). We wished to
      characterize prevalence and types of headaches in SLE and find out if headache is
      associated with disease, personality traits, or other psychological factors.
      METHODS: Fifty-eight consecutive Caucasian patients with SLE were given a
      clinical examination. We recorded SLE disease activity according to the SLE
      Disease Activity Index, types of headache according to International Headache
      Society criteria, and personality traits and emotional status according to
      Minnesota Multiphasic Personality Inventory-2 and Beck Depression Inventory
      (BDI). RESULTS: Thirty-eight SLE patients (66%) were headache sufferers; of
      these, 22 patients (38%) had migraine and 21 (36%) had tension-type headache.
      Headaches were not associated with disease activity or any other disease
      associated variable, including tests for antiphospholipid antibodies. Migraine
      was associated only with a tendency to social isolation and anxiety, while
      tension-type headache was associated with psychological distress, such as
      anxiety, somatic complaints, reduced energy, mental tension, social discomfort
      and withdrawal, and depressive mood according to the BDI. CONCLUSION; Migraine
      and tension-type headaches occur frequently in patients with SLE. Migraine shows
      the same clinical presentation as in a non-SLE population, and may not be part of
      a neuropsychiatric disease spectrum. This also applies to tension-type headache,
      which in contrast to migraine shows some associations with emotional and
      personality traits, and could represent components of a chronic pain syndrome.

PMID- 11327250
TI  - Longterm beneficial effect of chloroquine diphosphate on lipoprotein profile in
      lupus patients with and without steroid therapy.
AB  - OBJECTIVE: To investigate the influence of chloroquine diphosphate (CDP) alone
      and in combination with corticosteroids on systemic lupus erythematosus (SLE)
      lipoproteins. METHODS: Fasting lipid profiles were performed in 60 consecutive
      female patients with SLE and in 30 controls. All SLE patients had minor disease
      activity and were divided according to current therapy in 4 groups: No therapy;
      prednisone (Pred group; < 15 mg prednisone daily); CDP (250 mg daily); and Pred +
      CDP. RESULTS: There were no significant differences of age, race, and disease
      duration among SLE groups. All patients had SLEDAI scores < or = 4 and prednisone
      dose was similar in the 2 groups taking this drug. The CDP group had
      significantly higher levels of high density lipoprotein cholesterol (HDL-c)
      levels compared to No therapy group (p < 0.05), which were similar to those
      detected in healthy controls. In addition, higher levels of HDL-c and lower
      levels of triglycerides and very low density lipoprotein cholesterol levels (VLDL
      c) were detected in Pred + CDP compared to Pred (p < 0.05). CONCLUSION: CDP alone
      or added to corticosteroid therapy has a beneficial effect in SLE
      dyslipoproteinemia, particularly in increasing HDL-c levels. Additionally, this
      drug seems to revert the increased hepatic synthesis of lipoproteins induced by
      corticosteroids as suggested by the concomitant decrease of triglycerides and
      VLDL-c levels in SLE patients taking the combined regimen.

PMID- 11327251
TI  - Treatment of Raynaud's phenomenon with intravenous prostaglandin E1alpha
      cyclodextrin improves endothelial cell injury in systemic sclerosis.
AB  - OBJECTIVE: To evaluate the efficacy and safety of prostaglandin (PG) E1alpha
      cyclodextrin for Raynaud's phenomenon (RP) secondary to systemic sclerosis (SSc)
      and its effect on variables of immune activation and endothelial injury in SSc
      such as tumor necrosis factor-alpha (TNF-alpha), soluble interleukin 2 receptor
      (sIL-2R), circulating intercellular adhesion molecule-1 (cICAM-1), von Willebrand
      factor (vWF), and tissue-type plasminogen activator (t-PA). METHODS: We studied
      36 women with SSc, 24 of them given three 60 microg intravenous PGE1alpha
      cyclodextrin infusions on 5 consecutive days at 6 week intervals during the
      winter. RP symptoms and healing of digital lesions were evaluated. Twenty age
      matched healthy women were the controls. TNF-alpha, sIL-2R, cICAM-1, vWF, and t
      PA were measured after the first and last infusion of PGEE1alpha-cyclodextrin and
      correlated with clinical features. RESULTS: RP symptoms improved in 87% of the
      patients. The benefit of each 5 day cycle lasted 4 or more weeks in 75%.
      PGE1alpha-cyclodextrin reduced the daily frequency of RP symptoms by 20% (p <
      0.05), 41% (p < 0.005), and 53% (p < 0.0005) from baseline after the 1st, 2nd,
      and 3rd infusions, respectively. The severity of the attacks was reduced to a
      limited degree. In 12 of the 14 patients with digital lesions, these healed
      completely. Ten patients had mild side effects during treatment (headache,
      increased intestinal motility, flushing). TNF-alpha, sIL-2R, cICAM-1, vWF, and t
      PA plasma concentrations were significantly higher in patients with SSc than
      controls (p < 0.05, p < 0.001). TNF-alpha, sIL-2R, and cICAM-1 were higher in
      diffuse SSc and patients with lung involvement. The plasma levels of cICAM-1 and
      t-PA were significantly reduced after the 1st infusion of PGE1alpha-cyclodextrin
      (both p < 0.005) and further reduced after the last (p < 0.0005 and p < 0.005).
      CONCLUSION: PGE1alpha-cyclodextrin reduces RP symptoms and plasma levels of the
      markers of endothelial injury in SSc, suggesting that an improvement of
      endothelial dysfunction contributes to its prolonged therapeutic effect.

PMID- 11327252
TI  - Clinical and immunological characteristics of elderly onset Sjogren's syndrome: a
      comparison with younger onset disease.
AB  - OBJECTIVE: To compare the clinical and laboratory characteristics of patients
      with primary Sjogren's syndrome (SS) with an elderly onset to those with a
      younger onset. METHODS: The study group comprised 85 consecutive patients (79
      women and 6 men) attending the Sjogren's clinic. Primary SS was diagnosed
      according to the San Diego criteria. Elderly onset disease (EOD) was determined
      as the appearance of symptoms suggestive of SS after age 65. Clinical and
      laboratory variables for EOD were compared to those of a younger onset disease
      (YOD). Salivary and serum samples of all patients were examined for
      concentrations of interleukin 6 (IL-6) and hyaluronic acid (HA). RESULTS:
      Seventeen patients with SS (20%) matched the definition of EOD and their median
      disease onset was 71 years (range 65-80). No significant differences were noted
      in the clinical disease manifestations between the 2 groups of patients.
      Rheumatoid factor and anti-Ro(SSA) antibodies were more common in the YOD group
      (p = 0.012 and p = 0.023, respectively). Significant elevations of salivary IL-6
      and HA levels were detected in the YOD group compared to the EOD group with SS
      (17.3 +/- 3.6 vs 8.8 +/- 2.1 pg/ml and 230.2 +/- 41.1 vs 128.8 +/- 33.3 ng/ml,
      respectively) (p < 0.0001). CONCLUSION: EOD SS has somewhat milder clinical
      symptoms with fewer immunological manifestations than YOD. The elevations of
      salivary IL-6 and HA in the younger group of SS patients support in part the
      differences in the inflammatory process between the 2 groups.

PMID- 11327253
TI  - How significant is sensorineural hearing loss in primary Sjogren's syndrome? An
      individually matched case-control study.
AB  - OBJECTIVE: We evaluated whether sensorineural loss and vestibular abnormalities
      are common in patients with primary Sjogren's syndrome (pSS) and whether such
      abnormalities are clinically significant. METHODS: In an individually matched
      case-control design, 48 patients with pSS underwent complete audiovestibular
      evaluation along with 48 age and sex matched individuals without otologic
      problems. Differences of > 20 dB between patient and control ears at any
      frequency tested were considered to be significant. RESULTS: Significant
      differences in hearing loss were seen at 4,000 Hz (6 vs 0 ears; p = 0.03) and at
      8,000 Hz (9 vs 0 ears; p = 0.003). Small differences in hearing acuity were also
      observed in the lower frequencies, but the absolute mean difference was < 3 dB. A
      decrease of at least 60 dB in hearing acuity at any frequency up to 4,000 Hz was
      seen only in 3 elderly pSS patients. Abnormal brainstem auditory evoked responses
      were recorded in 7 patients and 5 controls, but no patient had retrocochlear
      lesions identified on magnetic resonance imaging. Four patients in each group had
      abnormalities on electronystagmography. CONCLUSION: pSS is associated with
      sensorineural hearing loss affecting preferentially the high frequencies, but
      clinically significant defects are not common. There is no evidence of
      retrocochlear disease or increased vestibular involvement in pSS.

PMID- 11327254
TI  - Musculoskeletal manifestations in patients positive for human immunodeficiency
      virus: correlation with CD4 count.
AB  - OBJECTIVE: To determine the relationship between the CD4+ lymphocyte count and
      musculoskeletal manifestations of human immunodeficiency virus (HIV) infection.
      METHODS: All patients from 1991 to 1998 who were positive for HIV with
      osteoarticular manifestations were reviewed retrospectively. HIV positivity was
      confirmed by ELISA and Western blot. CD4 count was performed by flow cytometry.
      RESULTS: We studied 74 patients with osteoarticular manifestations. The study
      group comprised 61 men (82.4%) and 13 women (17.5%) with a mean age of 34.2 years
      (range 17-62). Fifty-two patients were iv drug users (70.3%). Septic arthritis
      was present in 20 cases (23.0%), soft tissue infections in 9 cases (12.2%),
      spondyloarthropathies in 6 cases (8.1%), lymphomas in 9 cases (12.2%),
      osteomyelitis in 6 (8.1%), and 24 miscellaneous cases (32.4%). The mean CD4 count
      was as follows: septic arthritis 164.7 cells/mm3, soft tissue involvement 127.1
      cells/mm3, spondyloarthropathies 245.8 cells/mm3, lymphoma 132.8 cells/mm3, and
      osteomyelitis 233.6 cells/mm3. CONCLUSION: Osteoarticular manifestations in the
      setting of HIV infection tend to be predominantly infectious. S. aureus is the
      microorganism most frequently involved. Ostearticular infections always appeared
      when the CD4 count was < 200 and pyomyositis and lymphoma appeared when CD4 was <
      150. CD4 counts may be useful predictors to determine the type of musculoskeletal
      manifestation.

PMID- 11327255
TI  - Complement and cell mediated cytotoxicity by antiendothelial cell antibodies in
      Takayasu's arteritis.
AB  - OBJECTIVE: To study complement and cell mediated cytotoxicity by antiendothelial
      cell antibodies (AECA) in Takayasu's arteritis (TA). METHODS: Complement
      dependent cytotoxicity (CDC) and antibody dependent cellular cytotoxicity (ADCC)
      of AECA positive/negative TA sera were investigated by colorimetric MTT and 51Cr
      release assays, respectively, using human umbilical vein endothelial cells
      (HUVEC) as targets. RESULTS: Seven of 12 (58%) sera positive for IgG and/or IgM
      AECA exhibited CDC in comparison to none of the 13 AECA negative sera (p =
      0.0052). The median value of CDC of the AECA positive group was 14% (range 13
      21%) and that of the AECA negative group was 1% (p = 0.0012). Interleukin 1beta
      (10 U/ml) treatment of HUVEC resulted in enhancement in CDC of 6 of the 7 AECA
      positive cytotoxic sera, the median enhancement being 17% (range 7-29%). Tumor
      necrosis factor-alpha (100 U/ml) treatment of the targets resulted in a median
      enhancement by 36% (range 25-55%) in the CDC of 3 of these 7 sera. No sera
      exhibited ADCC at any of the effector:target ratios tested (10:1 to 100:1).
      CONCLUSION: AECA in TA mediate CDC against endothelial cells and may have a
      pathogenic role in the perpetuation of vascular damage in this disease.

PMID- 11327256
TI  - Analysis of calcium deposits in calcific periarthritis.
AB  - OBJECTIVE: To determine if hydroxyapatite (HAP), octacalcuim phosphate (OCP), or
      tricalcium phosphate (TCP) can be found in the calcium deposits in calcific
      periarthritis. METHODS: Thirty-six specimens from 34 patients who had acute
      inflammation and roentgenographically recognized calcification in soft tissue
      were analyzed. Twenty-three patients with calcific tendinitis in the shoulder and
      11 with calcific periarthritis at other sites were included. We prepared 2 kinds
      of samples from each specimen; a dried sample (washed and dried calcific
      deposit), and a sample heated to 1,000 degrees C. All were analyzed by X-ray
      diffraction, Raman spectroscopy, infrared absorption spectroscopy, and X-ray
      fluorescence spectrometry for calcium and phosphorus molar ratio. Synthetic HAP
      was used as the control in each analysis. RESULTS: The X-ray diffraction patterns
      of all dried samples were similar to those of HAP and carbonate apatite. We found
      no diffraction patterns of OCP or TCP. However, an OH- group at 3570cm(-1) was
      observed with Raman spectroscopy for samples heated to 1,000 degrees C and
      synthetic HAP, but not for the dried samples. Infrared absorption spectroscopy
      also confirmed an OH- group for samples heated to 1,000 degrees C and synthetic
      HAP, and confirmed that dried samples contained carbonate. CONCLUSION: Calcium
      deposits are composed of carbonate apatite. HAP, OCP, and TCP were not identified
      in any deposits.

PMID- 11327257
TI  - Diacerein reduces the excess synthesis of bone remodeling factors by human
      osteoblast cells from osteoarthritic subchondral bone.
AB  - OBJECTIVE: Although cartilage degradation characterizes osteoarthritis (OA),
      there is evidence that remodeling of subchondral bone in this disease is a
      contributing factor. Therapeutic strategies to modify the metabolism of
      subchondral bone osteoblasts may be indicated to treat OA. We studied the effects
      of diacerein and rhein on the metabolic and inflammatory variables of OA
      subchondral osteoblasts. METHODS: Human OA primary subchondral osteoblast cells
      were used. The effect of diacerein and rhein at therapeutic concentrations (5-20
      microg/ml) was determined by osteoblast phenotypic factors, alkaline phosphatase,
      osteocalcin, and cAMP; on metabolic agents urokinase plasminogen activator (uPA),
      plasminogen activator inhibitor-1 (PAI-1), and insulin-like growth factor-1 (IGF
      1); and on inflammatory mediators interleukin 6 (IL-6), prostaglandin E2 (PGE2),
      and cyclooxygenase-2 (COX-2). RESULTS: Diacerein and rhein did not affect either
      basal and 1,25(OH)2D3 induced alkaline phosphatase or parathyroid hormone (PTH)
      stimulated cAMP formation. Conversely, they dose dependently and statistically
      inhibited 1,25(OH)2D3 induced osteocalcin release, a situation explained by a
      reduction of mRNA levels for osteocalcin. Of the metabolic factors, they
      inhibited the production of uPA, with rhein showing slightly more potency;
      inhibitions of 69% and 57% were reached at the highest concentration (20
      microg/ml) of rhein and diacerein, respectively. Both drugs also inhibited the
      PAI-1 level, albeit at a much lower level than for uPA. Interestingly,
      determination of the uPA/PAI1 ratio revealed that both drugs inhibited it about
      55%, suggesting a decrease in uPA activity. In contrast, IGF-1 levels only
      increased slightly when cells were treated with rhein but not with diacerein. A
      transient dose dependent effect was found on IL-6 production; an inhibition was
      noted at low drug concentrations, which returned to basal levels at the highest
      concentration tested. PGE2 levels increased exponentially and were related to a
      concomitant increase in COX-2 levels in response to both drugs. CONCLUSION: Our
      data indicate that diacerein and rhein do not appear to affect OA subchondral
      bone cells' basal cellular metabolism, yet both agents reveal a direct effect at
      reducing the synthetic activities of osteoblasts, which could be responsible for
      abnormal subchondral bone remodeling occurring during the course of OA.

PMID- 11327258
TI  - The effects of orally administered diacerein on cartilage and subchondral bone in
      an ovine model of osteoarthritis.
AB  - OBJECTIVE: An ovine model of osteoarthritis (OA) induced by bilateral lateral
      meniscectomy (BLM) was used to evaluate in vivo effects of the slow acting
      antiarthritic drug diacerein (DIA) on degenerative changes in cartilage and
      subchondral bone of the operated joints. METHODS: Twenty of 30 adult age matched
      Merino wethers were subjected to BLM in the knee joints and the remainder served
      as non-operated controls (NOC). Half of the BLM group (n = 10) were given DIA (25
      mg/kg orally) daily for 3 mo, then 50 mg/kg daily for a further 6 mo. The
      remainder of the meniscectomized (MEN) group served as OA controls. Five DIA, 5
      MEN, and 5 NOC animals were sacrificed at 3 mo and the remainder at 9 mo
      postsurgery. One knee joint of each animal was used for bone mineral density
      (BMD) studies. Osteochondral slabs from the lateral femoral condyle and lateral
      tibial plateau were cut from the contralateral joint and were processed for
      histological and histomorphometric examination to assess the cartilage and
      subchondral bone changes. RESULTS: No significant difference was observed in the
      modified Mankin scores for cartilage from the DIA and MEN groups at 3 or 9 mo.
      However, in animals treated with DIA, the thickness of cartilage (p = 0.05) and
      subchondral bone (p = 0.05) in the lesion (middle) zone of the lateral tibial
      plateau were decreased relative to the corresponding zone of the MEN group at 3
      mo (p = 0.05). At 9 mo subchondral bone thickness in this zone remained the same
      as NOC but BMD, which included both subchondral and trabecular bone, was
      significantly increased relative to the NOC group (p = 0.01). In contrast, the
      subchondral bone thickness of the outer zone of lateral tibial plateau and
      lateral femoral condyle of both MEN and DIA groups increased after 9 mo, while
      BMD remained the same as in the NOC. CONCLUSION: DIA treatment of meniscectomized
      animals mediated selective responses of cartilage and subchondral bone to the
      altered mechanical stresses induced across the joints by this procedure. While
      subchondral bone thickness in tibial lesion sites was reduced, cartilage and bone
      proliferation at the outer joint margins, a region where osteophyte formation
      occurred, were enhanced, suggesting that DIA supported the processes of repair
      and endochondral ossification.

PMID- 11327259
TI  - Regulation of cartilage collagenase by doxycycline.
AB  - OBJECTIVE: To investigate the ability of doxycycline to modulate collagenases,
      cytokines, and cytokine receptors in chondrocytes from osteoarthritic (OA)
      cartilage. METHODS: Chondrocytes were isolated from human OA cartilage and
      treated with doxycycline. Synthesis of collagenases, cytokines, and cytokine
      receptors was quantified by Northern and Western blot analysis and RNase
      protection assay. RESULTS: We observed significant inhibition of matrix
      metalloproteinases (MMP-1) and MMP-13 mRNA and protein production by
      chondrocytes, isolated from OA cartilage, after treatment with doxycycline. The
      decrease in collagenase protein level paralleled a decrease in mRNA for these
      enzymes, suggesting a transcriptional/posttranscriptional level of control. In
      addition, treatment with 10 microg/ml doxycycline resulted in 2.2-fold
      upregulation of transforming growth factor (TGF-beta3) and a significant decrease
      of interleukin 1alpha (IL-1alpha), IL-1beta, and IL-6 mRNA. Upregulation of TGF
      beta RI and TGF-beta RII was also detected. These cytokines are known to affect
      collagenase expression and could contribute to inhibition of MMP-1 and MMP-13
      production by OA chondrocytes. A decrease in IL-1alpha, IL-1beta, and IL-6 would
      reduce stimulation of MMP production, while an increase in TGF-83 would lead to
      downregulation of local proinflammatory cytokine production as well as of the
      collagenases themselves. CONCLUSION: Our findings show that a decrease in MMP-1
      and MMP-13 collagenase production by articular chondrocytes in response to
      treatment with doxycycline can be explained by a regulatory effect of doxycycline
      on the production of cytokine and cytokine receptors.

PMID- 11327260
TI  - Muhammad Asim Khan. Portrait of a rheumatologist as a great artist.

PMID- 11327261
TI  - Sulfasalazine for the management of juvenile rheumatoid arthritis.
AB  - OBJECTIVE: Sulfasalazine (SSZ) has regulatory approval for treatment of
      inflammatory bowel disease in children and adults, and for use as a slow acting
      agent in adult rheumatoid arthritis (RA). This report surveys the literature for
      experience with SSZ in juvenile RA. METHODS: Medline, Excerpta Medica, and
      Derwent were searched under the terms juvenile, rheumatoid, arthritis, and
      sulfasalazine. RESULTS: The search found reports of experience in 550 patients,
      of whom about half had pauciarticular and nearly one-third polyarticular disease.
      The studies generally reported at least some drug associated benefit in all
      subtypes. Some identified late onset pauciarticular disease as most responsive,
      but others reported poly- and pauciarticular response rates about the same.
      Systemic onset disease responded poorly and showed a substantial incidence of
      intolerance in the form of serum sickness. Most studies showed useful disease
      control in spondylitis. Overall, the patterns of toxicity and intolerance were
      close to those seen in adult SSZ recipients, with the possible exception of the
      serum sickness-like response. CONCLUSION: SSZ has demonstrated useful
      antirheumatic activity and can contribute to the care of selected patients.

PMID- 11327262
TI  - Point prevalence of cardiac abnormalities in children with systemic lupus
      erythematosus.
AB  - OBJECTIVE: To determine the point prevalence and pattern of silent cardiac
      abnormalities and associations with suspected risk factors in a sample of
      children with systemic lupus erythematosus (SLE). METHODS: Cross-sectional
      analysis of 19 children with SLE from a referral-based rheumatology clinic at an
      urban children's hospital. Patients were eligible if they were 20 years of age or
      younger and classified with SLE using the revised criteria of the American
      College of Rheumatology. Each patient completed a survey, physical examination,
      standard 12-lead electrocardiogram (ECG), echocardiogram, and had laboratory
      determinations of complement, triglyceride, and cholesterol levels. RESULTS: Six
      patients (32%) had cardiac abnormalities on ECG or echocardiogram. In 3, the
      abnormalities were mild and considered within the normal range. In 5, the
      abnormalities were considered silent. These abnormalities included ischemic
      changes (3 patients), valvular insufficiency (3 patients), ventricular
      repolarization defects (2 patients), cardiac enlargement (1 patient), and
      ventricular dysfunction (1 patient). Only a recent history of palpitations was
      significantly associated with the presence of cardiac abnormalities (p = 0.04).
      CONCLUSIONS: Silent cardiac abnormalities can occur in children with SLE. A
      recent history of palpitations may be associated with cardiac abnormalities.
      Routine evaluation of children with SLE using ECG and echocardiogram may help
      screen for these abnormalities. However, future studies comprising larger sample
      sizes and longitudinal followup will be required to determine the natural history
      of cardiac abnormalities in children with SLE and to identify risk factors.

PMID- 11327263
TI  - Anti-alpha-fodrin antibodies in Sjogren's syndrome in children.
AB  - OBJECTIVE: To investigate the prevalence of anti-alpha-fodrin antibody specific
      for adult Sjogren's syndrome (SS) in patients with juvenile onset SS. METHODS:
      Serum anti-alpha-fodrin antibody was examined in 15 patients with juvenile SS (11
      cases of primary SS and 4 secondary SS) and in 16 children with systemic lupus
      erythematosus (SLE) by Western blot analysis using a recombinant 120 kDa alpha
      fodrin fusion protein. RESULTS: All the 15 serum samples from patients with SS
      reacted with a recombinant alpha-fodrin fusion protein in Western blot analysis.
      In contrast, reactivity was found in only 2 of the 16 patients with SLE. The
      clinical features of the 15 patients with juvenile onset SS were very specific;
      only 4 patients complained of dryness, while 6 had abnormal excretion ability.
      Salivary gland enlargement was the most common clinical manifestation.
      Characteristic laboratory findings in juvenile onset SS included a higher
      prevalence of antinuclear antibodies, anti-SSA/Ro antibodies, and rheumatoid
      factor, as well as increased erythrocyte sedimentation rate and
      hypergammaglobulinemia. CONCLUSION: The pathogenesis of juvenile SS seems to be
      the same as that of adult SS, although subjective symptoms of dryness are less
      frequent in juvenile cases. This discrepancy may indicate that SS is a slowly
      progressive disease with a long time span. The anti-alpha-fodrin antibody is
      likely to be a reliable diagnostic marker for juvenile SS.

PMID- 11327264
TI  - Methotrexate as a possible trigger of macrophage activation syndrome in systemic
      juvenile idiopathic arthritis.
AB  - Macrophage activation syndrome (MAS) is a potentially life threatening
      complication of chronic rheumatic diseases, particularly systemic juvenile
      idiopathic arthritis (JIA). A number of triggers have been related to the
      development of MAS, including viral infections, nonsteroidal antiinflammatory
      drug therapy, and gold salt injections. We describe a patient with systemic JIA
      who developed MAS shortly after receiving methotrexate, suggesting that this drug
      can be regarded as a potential trigger of MAS in children with JIA.

PMID- 11327265
TI  - Treatment of Felty's syndrome with leflunomide.
AB  - Felty's syndrome (FS) is a rare manifestation of severe rheumatoid arthritis
      (RA). It is an immune mediated inflammatory process, usually treated with
      standard disease modifying antirheumatic drugs. We describe a case of severe FS
      that developed in a patient receiving methotrexate therapy for RA. Treatment with
      etanercept resulted in severe allergic cutaneous reactions. The patient
      subsequently responded to treatment with leflunomide. The response included
      dramatic improvement of leukopenia and neutropenia as well as excellent control
      of his arthritis. Leflunomide has recently been used effectively for the
      treatment of RA and may be useful for the management of patients with FS.

PMID- 11327267
TI  - Systemic lupus erythematosus presenting as "one-and-a-half syndrome".

PMID- 11327266
TI  - Unusual presentation of polyarteritis nodosa.
AB  - We describe an unusual presentation of a localized form of polyarteritis nodosa
      (PAN) manifested by acute onset of severe calf pain. Biopsies of the
      gastrocnemius muscle and fascia revealed an acute necrotizing arteritis with
      fasciitis. The lumens of affected vessels were occluded by thrombi. PAN localized
      to calf muscles is extremely rare. To our knowledge this is the first report of
      evidence of fascial involvement believed to contribute to the severity of the
      clinical features of PAN. The occurrence of multiple intraluminal thrombi in
      conjunction with anticardiolipin antibodies suggested the possibility of a
      coexisting coagulopathy, and they were also likely contributors to the severity
      of the pain.

PMID- 11327268
TI  - Primary patellar T cell lymphoma: an unusual cause of monoarthritis.

PMID- 11327269
TI  - Renal granuloma and glomerulonephritis in Wegener's granulomatosis.

PMID- 11327270
TI  - Links between radiological change, disability, and pathology in rheumatoid
      arthritis.
AB  - The relationship between the development of radiographic joint destruction in
      rheumatoid arthritis and its longterm consequences for the patient is not well
      understood. Two objectives for further research have been identified: elucidating
      this relationship and relating pathological processes to the features visible on
      radiographs. Extrapolation from a proposed model suggests that if radiographic
      progression is suppressed early in the disease, it might take many years before
      the benefit can be clearly appreciated against a background of variation within
      individual patients. Two approaches have recently been brought to bear on this
      issue, including a detailed modeling of medium term observations from a single
      dataset and a review of a large number of published studies. There are a number
      of reservations about the notion of a minimum clinically important change, but
      one possibility for defining such a change for radiographs is in relation to
      longterm functional outcome.

PMID- 11327271
TI  - Recent rheumatoid arthritis clinical trials using radiographic endpoints--updated
      research agenda.
AB  - Recent randomized controlled trials of traditional and newly developed therapies
      provide evidence that we have interventions that potentially slow or prevent
      structural damage in active rheumatoid arthritis, as measured using radiography.
      These trials also provide a unique opportunity for exploratory data analysis to
      generate hypotheses apropos the pathogenesis and determinants of radiographic
      progression and functional disability; they also facilitate further study of the
      methodological issues regarding imaging measurement.

PMID- 11327272
TI  - Foundations of the minimal clinically important difference for imaging.
AB  - This article develops a generic conceptual framework for defining and validating
      the concept of minimal clinically important difference. We propose 3 approaches.
      The first uses statistical descriptions of the population ("distribution based"),
      the second relies on experts ("opinion based"), and a third is based on
      sequential hypothesis formation and testing ("predictive/data driven based"). The
      first 2 approaches serve as proxies for the third, which is an experimentally
      driven approach, asking such questions as "What carries the least penalty?" or
      "What imparts the greatest gain?" As an experimental approach, it has the
      expected drawbacks, including the need for greater resources, and the need to
      tolerate trial and error en route, compared to the other 2 models.

PMID- 11327273
TI  - Reliability of measures of disease activity and disease damage in rheumatoid
      arthritis: implications for smallest detectable difference, minimal clinically
      important difference, and analysis of treatment effects in randomized controlled
      trials.
AB  - We evaluate measurement properties of common rheumatoid arthritis (RA)
      assessments. Included are a comprehensive literature review and new data on the
      reliability and smallest detectable difference (SDD) for different classes of
      these measures. We found that certain common measures such as joint counts, pain,
      and patient global all had poor reliability and showed large SDD compared to
      multi-item measures of physical/psychological function or compared to
      radiographic measures. We discuss the implications of these findings on the use
      of composite endpoints such as the ACR20 or the EULAR responder index in RA
      clinical trials, particularly the introduction of misclassification bias that
      arises from differential measurement error. Finally, we consider generically how
      the concept of the SDD might or might not relate to the concept of the minimal
      clinically important difference.

PMID- 11327274
TI  - Minimal clinically important difference in radiological progression of joint
      damage over 1 year in rheumatoid arthritis: preliminary results of a validation
      study with clinical experts.
AB  - To determine the minimal clinically important difference (MCID) between hand and
      foot films with a 1 year interval assessed with the Sharp/van der Heijde or
      Larsen/Scott scoring method. Progression scores of the 2 methods were compared
      with the opinion of an international expert panel on clinical relevance of
      radiological joint damage in 4 predefined clinical settings. The expert panel
      consisted of 3 rheumatologists, who evaluated 46 pairs of hand and foot films,
      taken with 1 year intervals, of patients with early rheumatoid arthritis.
      Receiver operating characteristics curves analyzed the accuracy of different
      threshold values (progression scores) of the 2 scoring methods to detect the
      presence or absence of clinically important difference, as defined by the expert
      panel as external criterion. The threshold value with the highest accuracy was
      subsequently chosen as the score representing the MCID. Five Sharp/van der Heijde
      units and 2 Larsen/Scott units were the best cutoffs. The accompanying
      sensitivities ranged from 77% to 100% for the Sharp/van der Heijde method and
      from 73% to 84% for the Larsen/Scott method for the 4 clinical settings. The
      specificities were between 78% and 84% for the Sharp/van der Heijde method and
      between 74% and 94% for the Larsen/Scott method. The smallest progression score
      that can be detected apart from interobserver measurement error, the smallest
      detectable difference (SDD), was equal to or larger than the calculated MCID, 5
      Sharp/van der Heijde units and 6 Larsen/Scott units in our study, if the mean
      progression scores of the same 2 observers were used. The SDD is a conservative
      estimate of the MCID; our panel rated progression at or below this level as
      clinically significant.

PMID- 11327275
TI  - Robustness and generalizability of smallest detectable difference in radiological
      progression.
AB  - The smallest detectable difference (SDD) reflects that component of a measure
      statistically attributable to error from the measurement process itself. As such
      it is an irreducible component of the inherent variability in measurements in
      clinical trials and will affect their design, whether randomized or
      observational. Even though the application of the SDD concept to assaying
      radiographs in rheumatoid arthritis is relatively new and not well understood,
      systematic work on the influences of radiographic SDD can be done. This report
      describes the effects of a number of clinical aspects of the disease and
      operational aspects of trials on the values of the SDD of radiographic
      progression data. We show that if conditions affecting SDD are known and kept
      constant across datasets, the SDD of radiological progression from one study may
      be generalizable to other studies. However, if any one condition varies, the SDD
      is distinctly unrobust and cannot be generalized to other studies.

PMID- 11327276
TI  - Minimal clinically important difference in plain films in RA: group discussions,
      conclusions, and recommendations. OMERACT Imaging Task Force.
AB  - Analysis of progression of structural damage on an individual patient level in
      randomized controlled trials provides extra information in addition to the
      analysis on a group level. A cutoff level is required to define which patients
      show progression and which patients do not. The objective of the mimimal
      clinically important difference (MCID) module for plain films was to elaborate
      the various concepts to determine a MCID for plain films, and if possible, to
      define a MCID for specific scoring methods. The module comprised preconference
      reading material, a plenary session, small group discussions, and a plenary
      report of the group sessions, combined with interactive voting. The following
      conclusions and recommendations were made: the smallest detectable difference
      (SDD) beyond measurement error is a good starting point to define MCID; SDD is
      study-specific; SDD should be reported for all radiographic endpoints used in a
      trial as a quality control; the expert panel approach is a reasonable method to
      define MCID, but defined in this way MCID may be smaller than current SDD; more
      research is needed to validate expert panel based MCID in different datasets and
      with different experts; a predictive, data driven MCID is the ultimate goal, but
      is not yet available; the SDD can be used as a proxy for MCID until a data driven
      MCID is available; analysis at the group level (comparison of means or medians)
      should remain primary in studies that include progression of joint damage as
      outcome measure; the proportion of patients showing more progression than the SDD
      is a secondary outcome measure.

PMID- 11327277
TI  - Magnetic resonance imaging and polymyalgia rheumatica.

PMID- 11327278
TI  - In vitro thrombin generation.

PMID- 11327279
TI  - Fibromyalgia and hypermobility.

PMID- 11327280
TI  - A distinct syndrome including features of systemic sclerosis, erosive rheumatoid
      arthritis, anti-topoisomerase antibody, and rheumatoid factor.

PMID- 11327281
TI  - Extracellular matrix interactions with osteoblasts in osteoarthritis. A
      preliminary report.

PMID- 11327282
TI  - DNA microsatellite markers for estrogen receptor-beta are not associated with
      systemic lupus erythematosus.

PMID- 11327283
TI  - Glucocorticoids but not NSAID abort attacks in hyper-IgD and periodic fever
      syndrome.

PMID- 11327285
TI  - Epilepsy surgery: guidelines for minimum standard equipment and organization.
AB  - These guidelines, developed by the Study Group on Functional Neurosurgery of the
      Italian Society of Neurosurgery, concern the minimum standard equipment and
      organization required to a center dealing with the surgical treatment of
      epilepsy. They include the general criteria for patient selection, the main
      presurgical diagnostic procedures able to define seizure characteristics and
      concomitant brain abnormalities, the standard surgical procedures utilized.
      "Cryptogenetic" as well as "symptomatic" epilepsies are considered.
      Recommendations are also provided for correct result assessment and follow-up
      evaluation. Guidelines presented here reflect a multidisciplinary consensus and
      expert opinion, based on scientific evidence and current clinical experience.

PMID- 11327286
TI  - Characterization of endothelial cells isolated by human meningiomas.
AB  - BACKGROUND: Meningiomas are common neoplasms of central nervous system
      characterized by a prominent angiogenesis in some histological subtypes and in
      some phase of their progression. Angiogenesis is a required event for the
      progression of solid tumor. However there are increasing evidences that the
      biological features of endothelial cells in the tumor other than the microvessel
      number dictate the behavior of cancer disease. In the present study we have
      tested the hypothesis that in vitro endothelial cells originated by human
      meningiomas have a different phenotype from that of normal capillary endothelial.
      METHODS: To isolate endothelial cells we have used a new technical approach
      principally based on collagenase digestion of the tissues followed by capture of
      endothelial cells obtained through molecules recognizing specific endothelial
      markers conjugated to magnetic beads. RESULTS: By using beads conjugated with a
      monoclonal antibody anti CD-36 we have separated with high efficiency and purity
      meningioma endothelial cells and established three cell cultures. These cells
      uptake acetylated LDL and express CD-31, CD-36, nitric oxide synthase type III,
      von Willebrand factor, which are specific markers of endothelial cells. Their
      mitogenic and motogenic potential in resting conditions or after stimulation with
      vascular endothelial growth factor-A is superimposable to that of normal
      capillary endothelial cells. However meningioma endothelial cells produce higher
      amount of interleukin-6 and of monocyte chemotactic peptide-1 than control cells.
      CONCLUSIONS: The establishment of a new and suitable technique to isolate
      endothelial cells from human cancers can be useful to learn more on angiogenic
      mechanisms in tumor progression. Furthermore, the data shown underline the
      possible pathogenic role in meningioma progression of infiltrating macrophages
      triggered by monocyte chemotactic peptide-1 released by tumor endothelial cells.

PMID- 11327287
TI  - The importance of substance P and calcitonin gene related peptide as vasodilator
      neuropeptide during acute phase of experimental posthemorrhagic vasospasm.
AB  - BACKGROUND: Several immunohistochemical studies conducted in the acute phase
      following SAH have demonstrated a marked depletion of certain peptides like
      Substance P (SP), Calcitonin Gene Related Peptide (CGRP) from the adventitia of
      perivascular nerves. The present experimental study was carried out with the aim
      of determining whether the depletion of these peptides could be a protection
      mechanism against the factors which sustain the vasospasm. METHODS: To accomplish
      this goal, we administered specific antiserum to block the potential effect of
      neuropeptides (SP and CGRP) prior to SAH. Our study tried also to realize whether
      difference can be demonstrated between endothelium-dependent (SP) and endothelium
      independent vasodilatory mechanisms (CGRP) during the acute phase ofvasospasm.
      Twenty-three rabbits were divided in 5 experimental groups: Group A included
      normal control animals, Group B included rabbits who received saline injection
      prior to SAH, Group C included animals who received preimmune serum, groups D and
      E included animals who received respectively antiserum against CGRP and against
      SP prior to SAH. The antisera were administered into the cisterna magna by means
      of percutaneous suboccipital puncture. After 15 minutes 1 ml of autologous non
      heparinized blood was injected in the same way. After 20 minutes the animals were
      sacrificed by cardiac perfusion. The basilar artery was removed by means of
      transclival approach and it was included in Epon 812. Mean diameters and luminal
      areas of the arteries were measured with morphometric method on sections of 2-3
      microm of thickness. RESULTS: The results showed a reduced mean diameter and
      luminal areas in the group B comparing to normal controls of the group A. A
      marked vasospasm is mainly evident in group D and E. In group C the vasospasm is
      not significantly different from that of group B. No significant difference was
      demonstrated between group D and group E. CONCLUSIONS: We can conclude that: 1)
      the marked depletion of neuropeptides in the early phases of vasospasm represents
      a functional phenomenon in order to reduce the effectiveness of spasmogenic
      stimula. In fact the inhibition of the activity of these neuropeptides worses the
      entity of the vasospasm. 2) During the acute phase of vasospasm the endothelium
      dependent vasodilatory mechanism is still functioning. No significant difference
      in the entity of vasospasm has been demonstrated between inhibition of SP
      (endothelium-dependent) and CGRP (endothelium-independent). Inactivation of such
      a mechanism occurs during late phases.

PMID- 11327288
TI  - Therapeutic indications in upper cervical spine instability. Considerations on 58
      cases.
AB  - BACKGROUND: The particular biomechanics of the upper cervical spine require, when
      trauma occurs, careful evaluation of the stability of the lesions, in order to
      guarantee the best possible therapeutic and prognostic approach. To date, there
      has been no uniformity of opinion in merit, especially with reference to
      treatment of odontoid fractures. It is necessary for this reason as much as for
      the opportune standardisation of the patients' classification parameters to
      establish what is meant by stability and which lesions are to be held as being
      unstable in the upper cervical spine. METHODS: All the cases of upper cervical
      spine instability treated in our Unit from '94 to date have been reviewed. Four
      fractures to the first cervical vertebra, 29 to the odontoid process, 9 isolated
      fractures in the C2 body, 12 hangman fractures, 7 fractures of the articular
      processes, 2 to the occipital condyles and 4 C1-C2 dislocations without fractures
      were localised. Using precise prognostic indexes as our classification criteria,
      56 of the 58 patients observed were addressed towards either conservative
      treatment or directly towards surgical treatment. In particular, 29 patients were
      conservatively treated with a collar or Halo-Vest. Twenty-seven surgical
      operations were carried out: 14 screw fixations, 6 anterior fixations using
      plates and screws, 4 rear ones using metal wire or wire with bone graft, 3
      odontectomy operations associated with posterior fixation. RESULTS: In the follow
      up, using a range of between three months to six years, good fusion with spine
      stabilisation was achieved in all the patients treated. In particular, surgery
      was carried out as the first therapeutic indication in 25 cases, obtaining
      excellent results. Surgery was necessary in only 2 cases after the failure of
      external stabilisation. CONCLUSIONS: The judgement passed on instability in
      traumatic lesions in the upper cervical spine represents the decisive factor in
      the choice of the therapeutic option. Instead of always opting for conservative
      treatment, in the case of C1-C2 fractures-luxations, and going ahead with surgery
      only when there is instability or non-fusion of the segments resulting after
      successive monitoring, we believe that the definition and standardisation of the
      prognostic factors is opportune, in order to provide patients with a specific
      solution, in such a way as to reduce the failure percentage of the first
      treatment and optimise the healing time.

PMID- 11327289
TI  - Value of MIB-1 labelling index (LI) in gliomas and its correlation with other
      prognostic factors. A clinicopathologic study.
AB  - BACKGROUND: In recent years, the monoclonal antibody MIB-1 has become the main
      factor to measure the proliferative potential of glial tumors. This antibody is
      equivalent to Ki-67, which is used in frozen sections, and reacts with a nuclear
      protein that is expressed through the cell cycle. We have investigated the value
      of MIB-1 Labelling Index (LI) as an independent prognostic factor in gliomas and
      its relationship with clinical and pathological parameters. METHODS: MIB-1 LI was
      determined in 139 gliomas by using the Streptavidin-Biotin Complex (SBC)
      immunohistochemical method. MIB-1 LI immunoreactivity was measured with an
      automatic cell counting system. Survival was studied by using the Kaplan-Meier
      bivariant analysis and Cox multivariant regression. RESULTS: In bivariant
      analysis MIB-1 LI increased with age, histological grade and a supratentorial
      lateral location. Only size and tumor grade were significant in Cox regression.
      CONCLUSIONS: Perhaps this proliferation marker is influenced by many factors
      which reduce its value as an isolated prognostic parameter.

PMID- 11327290
TI  - Prognostic factors in malignant melanoma patients with solitary or multiple brain
      metastases. Is there a role for surgery?
AB  - BACKGROUND: The aim of this study is to evaluate the prognostic parameters and
      treatment modalities of malignant melanoma patients with brain metastases.
      METHODS:  EXPERIMENTAL DESIGN: a retrospective study with a mean follow-up of 46
      months. SETTING: specialized Cancer Center. PATIENTS: the charts of 136 patients,
      treated in Roswell Park Cancer Institute, for melanoma brain metastases, were
      analyzed. INTERVENTIONS: all patients were treated surgically and in the majority
      adjuvant therapy was applied. MEASURES: survival and time of recurrence of
      patients and possible prognostic factors. RESULTS: PATIENTS who were treated
      surgically had a better one-year survival rate (28.3%), than patients who
      received radiotherapy and/or chemotherapy (6.67%) or patients who refused any
      kind of treatment (3.45%), (p=0.006). Prolonged survival after surgical treatment
      was found in patients with single metastatic lesions and in patients with
      multiple metastatic lesions. CONCLUSIONS: Melanoma patients with single
      metastatic lesions to the brain seem to do better after surgical treatment. The
      role of surgical intervention in patients with multiple brain metastases needs re
      evaluation from a big multicenter, prospective trial.

PMID- 11327291
TI  - Investigation and comparison of the effects of rehabilitation on balance and
      coordination problems in patients with posterior fossa and cerebellopontine angle
      tumours.
AB  - BACKGROUND: This study was planned to investigate and compare the effects of
      acute rehabilitation programme on balance and coordination problems in patients
      with posterior fossa and cerebellopontine angle tumours. METHODS: This study was
      carried out at Hacettepe University, School of Physical Therapy and
      Rehabilitation, neurosurgical rehabilitation unit on 40 patients whose ages
      varied between 18-60 years. Subjects were subdivided into two groups. Group I
      consisted of 20 patients with posterior fossa tumour, while the group II was
      composed of 20 patients with cerebellopontine angle tumour. Patients were
      evaluated according to the localisation of the tumour, the number of the surgical
      operations, the level of the surgical excision of the tumour, percent of having
      shunt, radiotherapy and chemotherapy. Balance problems were assessed according to
      Mokken's functional independence assessment scale in 5 selected positions and
      standing balance was also evaluated according to the method of Bohannon. The
      rehabilitation of the patients included balance and coordination training. The
      patients were re-evaluated before their discharge and the results of the two
      evaluations were compared. RESULTS: A significant improvement was found in the
      second group when pre- and post-treatment evaluations were compared. There were
      more coordination problems in group 1 in the pretreatment period. Both groups
      showed significant improvement of coordination problems after the treatment.
      However, this improvement was more obvious in the second group (p<0.05). There
      was a negative significant correlation between the decrease of balance problems
      and the amount of the tumour excided (I Group r=-0.51, II Group r=-0.57).
      CONCLUSIONS: It can be concluded that rehabilitation approaches are effective in
      balance and coordination problems observed in both tumour groups, but the
      responses to treatment are more obvious in the cerebellopontine angle tumours,
      which have better prognosis.

PMID- 11327292
TI  - Chiasmal cavernous malformation. A rare cause of acute visual loss.
AB  - A rare cause of acute visual loss due to a chiasmal cavernous malformation is
      presented. Acute visual loss was due to local hemorrhage and volume expansion of
      the cavernous malformation inside and outside of the optic chiasma. This unique
      location of cavernous malformation is associated with a risk of permanent loss of
      the vision. Cavernous malformations of optic chiasma should be carefully
      evaluated and considered for possible preventative surgical resection before it
      becomes symptomatic.

PMID- 11327293
TI  - Medulloblastoma in late adults. Case report and critical review of the
      literature.
AB  - BACKGROUND: Medulloblastoma in late adults (older than 65 years) is an
      exceptional occurrence; in fact only 8 cases are reported with complete clinical
      notes in the literature. METHODS: The authors describe a case of medulloblastoma
      occurring in a 68-year-old man and analyzed cases reported in the literature.
      RESULTS: The overall average age of the patients was 72.8 years (range 67-88
      years), and the male prevalence of this tumour (70% of cases) seems to be
      unrelated to age. There is a lateral predominance in late adults (77.7% of
      cases). Seven patients underwent operation and subsequently these patients
      underwent a course of radiation therapy. Only two patient was treated with
      postoperative chemotherapy. Median survival for seven patients treated was 43.2
      months (range 23-96 months). CONCLUSIONS: It is interesting to note that: 1)
      histological analysis revealed a classic type medulloblastoma (88.8% of cases)
      similar to the children: 2) site of the tumor is lateral similar to the adults
      (77.7% of cases).

PMID- 11327294
TI  - Lhermitte duclos disease and Cowden disease: clinical, pathological and
      neuroimaging study of a case.
AB  - The authors report the case of a 26-year-old female patient affected by Lhermitte
      Duclos disease and Cowden disease. Preoperative MRI allowed a correct diagnosis
      which was confirmed by pathological examination. The authors stress the
      possibility that Lhermitte Duclos and Cowden disease be a single phakomatosis;
      for this reason all the patients affected by Lhermitte-Duclos should be screened
      for the presence of multiple hamartomas or malignant neoplastic lesions typical
      of Cowden disease.

PMID- 11327295
TI  - Lumbosacral congenital dermal sinus presenting in a 52-year-old man. Case report.
AB  - Spinal congenital dermal sinus is a rare entity which results from failure of the
      neuroectoderm to separate from cutaneous ectoderm during the process of
      neurulation. This epithelium-lined tract forms a potential communication between
      the skin surface in the midline along the spine and the deeper tissues. We
      describe a case of an asymptomatic lumbosacral congenital dermal sinus in a 52
      year-old man. Microsurgical excision of dermal tract was performed with no
      postoperative complications and with a satisfactory cosmetic result. The authors
      stress the importance of an early neuroradiological and neurosurgical management
      of the lesion. The embryogenesis of this pathological condition and the possible
      complications are also discussed.

PMID- 11327296
TI  - Ubiquitinated neuronal inclusions in the neostriatum in patients with amyotrophic
      lateral sclerosis with and without dementia--a study of 60 patients 31 to 87
      years of age.
AB  - OBJECTIVE AND METHODS: Neuronal degeneration in amyotrophic lateral sclerosis
      (ALS) is associated with ubiquitinated cytoskeletal alterations in the motor
      neuron system. Ubiquitin-positive inclusions are also seen in the limbic system
      in ALS with dementia (ALS-D). Recently, similar inclusions were reported to occur
      in the neostriatum in a case of ALS-D. We, therefore, immunohistochemically
      examined the neostriatum from 60 patients with ALS and 60 control subjects.
      RESULTS: Two forms of ubiquitin-positive inclusions were found in the ALS
      neostriatum: rod-like inclusions in the large neurons and crescent-shaped
      inclusions in the small neurons. The former were found in 14 ALS and 18 control
      subjects, whereas the latter were specific to ALS; the crescent-shaped inclusions
      in small neurons were found in 27 ALS patients, and the immunohistochemical and
      ultrastructural features were identical to those of the extra-motor inclusions of
      ALS. Moreover, characteristic temporal lesions consistent with those seen in ALS
      D were found in 8 patients, of whom 2 had shown dementia. CONCLUSION: The present
      findings strongly suggest that neostriatal small neurons are also involved in the
      disease process in ALS.

PMID- 11327297
TI  - Familial amyotrophic lateral sclerosis with posterior column degeneration and
      basophilic inclusion bodies: a clinical, genetic and pathological study.
AB  - We report an autopsy case of familial amyotrophic lateral sclerosis (FALS). The
      patient was a Japanese woman with hereditary burden. Family history revealed 12
      patients with FALS over four generations. She developed muscle weakness of the
      proximal part of the upper extremities at age 42, followed by dysarthria,
      dysphagia, muscle weakness and atrophy in the lower extremities, spasticity,
      hyperreflexia and Babinski's sign. At age 44, she needed ventilatory support. At
      age 45, she died of bronchopneumonia. The total duration of the disease was three
      years and one month. Genetic study showed the absence of a mutation in the Cu/Zn
      superoxide dismutase-1 gene. Neuropathological examination revealed not only
      neuronal loss in the upper and lower motor neuron and Clarke's column, but also
      degeneration of the pyramidal tracts, middle root zone of the posterior column
      and posterior spinocerebellar tract. Bunina bodies and Lewy body-like inclusion
      bodies were absent. A few basophilic inclusion bodies were present in the neurons
      of the brain stem and anterior horn of the lumbar cord. Based on these clinical,
      genetic and pathological findings with a review of the literature, we concluded
      that our case was the first reported case of FALS with posterior column
      involvement and basophilic inclusion bodies.

PMID- 11327298
TI  - Expression of matrix metalloproteinase-9 and urinary-type plasminogen activator
      in Alzheimer's disease brain.
AB  - OBJECTIVE: Urinary-type plasminogen activator (uPA) binding to uPA receptor
      (uPAR) promotes the activation of matrix metalloproteinase-9 (MMP-9), which
      degrades amyloid beta protein (Abeta) in vitro. We investigated the expression of
      MMP-9, uPA, and uPAR in post-mortem brains from patients with Alzheimer's disease
      (AD) and those with vascular dementia (VD). MATERIAL AND METHODS: We used
      immunohistochemistry to examine the sections of the parietal lobe and hippocampus
      from 4 AD and 3 VD patients. The anti-MMP-9 antibody, anti-uPA antibody, and anti
      uPAR antibody were used to perform immunohistological analysis. RESULTS: In the
      brain tissues from the AD patients, we found expression of MMP-9 in the cytoplasm
      of neurons, neurofibrillary tangles, senile plaques, vascular walls and uPAR
      expression in the cytoplasm of neurons and vascular walls. uPA was detected only
      in the vascular walls. On the other hand, we could not find expression of MMP-9,
      uPAR and uPA in the brain tissues of the VD patients, except for the vascular
      walls. CONCLUSION: The neurons in the AD brains expressed MMP-9 and uPAR. MMP-9
      may be produced for the degradation of Abeta, but uPA, which activates MMP-9, was
      not immunolocalized to the neurons in the AD brains.

PMID- 11327299
TI  - Brain metastases of a malignant fibrous histiocytoma presenting as an acute
      cerebral hemorrhage.
AB  - Intracranial metastases from malignant fibrous histiocytoma (MFH) are rare,
      particularly with associated hemorrhage. This article reports one case and
      presents a review of the literature on this topic. A 55-year-old man presented
      with acute drowsiness, aphasia and right homonymous hemianopsia and hemiparesis.
      The first CT scan showed a left occipitoparietal hematoma and the second one,
      nodular, contrast-enhanced lesions. He had been previously operated on soft
      tissues MFH. Lung metastases developed subsequently. A craniotomy was performed
      with evacuation of the hematoma and total gross resection of the mass lesions.
      Microscopic examination disclosed a metastasis from a MFH. Neoangiogenesis,
      stimulated by angiogenic growth factors, seems to take part in this vascular,
      stroke-like event. Due to longer survivals of patients harboring systemic
      sarcomas, these tumors should be considered in the differential diagnosis of
      intracranial neoplasms, whether hemorrhagic or not. In particular, history of a
      previous soft tissue or heart tumor associated with lung metastasis should evoke
      the possibility of MFH metastasis.

PMID- 11327300
TI  - Anterior sacral meningocele in a patient with Marfan syndrome.
AB  - Anterior sacral meningocele has been reported to be associated with Marfan
      syndrome (MFS) in few cases, differently from dural ectasia appearing up to two
      thirds of affected patients. A new instance of this association is described in
      an 18-year-old man with Marfan syndrome, diagnosed upon MRI morphological
      evaluation which showed a huge cystic mass in the pelvic space. Surgical excision
      even if curative was not performed in consideration of a stationary picture after
      one year since diagnosis.

PMID- 11327301
TI  - Dysplastic glioneuronal lesion arising in the cerebellum: a clinicopathological,
      immunohistochemical and ultrastructural study.
AB  - We describe a case of dysplastic glioneuronal lesion in the right cerebellar
      hemisphere. A 13-year-old boy presented with headache since 1998. He had no
      neurological deficits. The computerized tomograph (CT) scan showed prominent
      calcification, and magnetic resonance imaging (MRI) revealed a non-enhancing mass
      of 15 x 15 x 5 cm in the right cerebellar hemisphere. The mass had low intensity
      in T1- and high intensity in T2-weighted images. Histologically, the lesion was
      composed of poorly defined small to intermediate sized cells arranged in
      fibrillar background. Although few neuronal cells having large nuclei with small
      nucleoli were present, no ganglion cells could be seen. Immunohistochemically,
      these poorly defined cells were non-reactive to various glial and neuronal
      markers. However, GFAP, synaptophysin, neurofilament and vimentin-reactive
      intercellular matrix and few nonneoplastic GFAP-positive glial cells and
      neurofilament-positive neuronal cells were seen. A very low MIB-1-labelling index
      of less than 0.1% was noted. Ultrastructurally, two different populations of the
      cells were seen. A few neuronal cells were larger and had an oval nucleus with
      small nucleolus and cytoplasm containing various cytoplasmic organelles, Golgi
      apparatus, mitochondria, ribosomes, lipofuscin, rough endoplasmic reticulum,
      microtubules and neurofilaments. Many other cells had a scant cytoplasm and thus
      poorly defined. Cytoplasmic processes with axono-dendritic synapses and foci of
      bundles of intermediate filaments were present in the intercellular areas of the
      lesion. Based on these radiological, histological and ultrastructural findings of
      the lesion of low proliferative potential, we considered it dysplastic in nature.

PMID- 11327302
TI  - Giant cell arteritis in a 19-year-old woman associated with vertebral artery
      aneurysm and subarachnoid hemorrhage.
AB  - Giant cell arteritis (GCA) is a disease chiefly found in elderly patients.
      Intracranial vessels are rarely involved in GCA. Here we report the case of a 19
      year-old woman with GCA in the basilar and vertebral arteries. Two weeks after
      the first symptoms, she developed an aneurysmatical dilatation of the right
      vertebral artery which ruptured leading to subarachnoid hemorrhage. Although the
      ruptured right vertebral artery was clipped neurosurgically, she died two days
      later. Autopsy revealed GCA with focal medial necrosis and intimal thickening of
      the vertebral arteries and the basilar artery. No other arteries were affected.
      In the involved vessels, the media exhibited C1q immunoreactivity. At the intimal
      site of the internal elastic lamina there were increased levels of elastase.
      Other arterial diseases showing the pattern of GCA were excluded. This case
      demonstrates that GCA is not necessarily restricted to elderly people. Moreover,
      this case shows that a GCA-induced aneurysm is a very rare reason for
      subarachnoid hemorrhage even in young adults.

PMID- 11327303
TI  - Early immunohistochemical detection of axonal damage and glial activation in
      extremely immature brains with periventricular leukomalacia.
AB  - Extremely low birth weight (ELBW) infants, who died at 12 hours to 7 days after
      birth, with periventricular leukomalacia (PVL), were examined by means of
      neuropathological and immunohistochemical methods. Fourteen infants without PVL
      were used as controls. Anti-beta-amyloid precursor protein (APP), glial
      fibrillary acidic protein (GFAP), and ionized calcium-binding adaptor molecule 1
      (Iba1) antibodies were used as markers for axonal damage, reactive astrocytes and
      activated microglia, respectively. Thirteen of 14 ELBW infants with PVL showed a
      widespread distribution of leukomalacia and 10 showed postnatal-onset of
      leukomalacia. In 12 of the 14 infants with PVL, regions of APP-reactive axons
      were found multifocally in the cerebral white matter, but 8 of them did not show
      coagulation necrosis on HE staining. GFAP-positive cells and Iba1-positive cells
      were markedly found in the white matter of all cases with PVL and slightly in all
      14 controls. These results indicated that in ELBW infants, the distribution and
      formation of PVL foci are widespread and characteristic and so may involve motor
      and intellectual abilities in ELBW infants. Therefore, the perinatal management
      to maintain an appropriate cerebral circulation and oxygenation may be very
      important.

PMID- 11327304
TI  - The evolution of the IUBMB-Nicholson maps.

PMID- 11327305
TI  - Public funding of intellectual curiosity.

PMID- 11327306
TI  - Macromolecular mimicry in translation initiation: a model for the initiation
      factor IF2 on the ribosome.
AB  - Protein biosynthesis in bacteria is controlled by a number of translation
      factors. Recent data based on comparison of sequence and structure data of
      translation factors have established a novel hypothesis for their interaction
      with the ribosome: initiation, elongation, and termination factors may use a
      common or partly overlapping binding site on the ribosome in a process of
      macromolecular mimicry of an A-site-bound tRNA. This paper reviews structural
      knowledge and tRNA macromolecular mimicry involvement of translation initiation
      factor IF2. Furthermore, a model is proposed for the factor and its interaction
      with the ribosome during the formation of the translation initiation complex.

PMID- 11327307
TI  - Genetic instabilities of triplet repeat sequences by recombination.
AB  - The expansion of triplet repeat sequences is an initial step in the disease
      etiology of a number of hereditary neurological disorders in humans. Diseases
      such as myotonic dystrophy, Huntington's, several spinocerebellar ataxias,
      fragile X syndrome, and Friedreich's ataxia are caused by the expansions of
      CTG.CAG, CGG.CCG, or GAA.TTC repeats. The mechanisms of the expansion process
      have been investigated intensely in E. coli, yeast, transgenic mice, mammalian
      cell culture, and in human clinical cases. Whereas studies from 1994-1999 have
      implicated DNA replication and repair at the paused synthesis sites due to the
      unusual conformations of the triplet repeat sequences, recent work has shown that
      homologous recombination (gene conversion) is a powerful mechanism for generating
      massive expansions, in addition to, or in concert with, replication and repair.

PMID- 11327308
TI  - Aberrant caveolin-1 expression in psoriasis: a signalling hypothesis.
AB  - A preliminary retrospective immunocytochemical study was conducted examining the
      expression of caveolin-1 in skin biopsies resected from clinically defined
      psoriatic subjects. These pilot investigations revealed a dramatic down
      regulation of caveolin-1 (a protein product of the caveolin supergene family
      known to regulate signal transduction events and cell cycle dynamics) in the
      hyperproliferative basal regions of the epidermis in all psoriatic biopsies
      examined when compared to normal control samples. These results lead us to
      hypothesise that caveolin-1 negatively regulates key signal transduction pathways
      in epidermal keratinocytes and through it's reduced expression in psoriasis,
      pertubations in keratinocyte cell signalling and abnormal cell differentiation
      ensue, events fundamental to the development of the psoriatic phenotype. Novel
      therapeutic strategies for the treatment of psoriasis based upon caveolin-1
      protein can be envisaged.

PMID- 11327309
TI  - Characterization of a retinoic acid responsive element in the human ets-1
      promoter.
AB  - The vitamin A metabolite retinoic acid (RA) is a powerful regulator of cellular
      proliferation and differentiation. The effects of RA on target gene expression
      are mediated by a family of ligand dependent nuclear transcription factors known
      as retinoic acid receptors (RAR). RARs have functional domains for retinoic acid
      binding, dimerization, and transactivation. RA response elements (RARE) found in
      the promoters of many genes consist of variable direct repeats of the sequence
      PuGGTCA spaced by five nucleotides (DR5). We have identified a novel DR5 element
      in the human ets-1 promoter. Mutational analysis of this site indicates that it
      is necessary for RA- and RAR-dependent activation of the ets-1 promoter. RARalpha
      can bind specifically to this site as determined by electrophoretic mobility
      shift analysis. Finally, RA mediates induction of the human ets-1 gene at the
      mRNA and protein levels. These data suggest that induction of ets-1 expression by
      RA is mediated by a novel retinoic acid response element in the promoter region
      of this gene.

PMID- 11327310
TI  - Molecular analysis of the Saccharomyces cerevisiae YHR076w gene.
AB  - Our results demonstrate that open reading frame (ORF) YHR076w on chromosome VIII
      of Saccharomyces cerevisiae that was previously described as a hypothetical gene
      is expressed. This ORF is transcribed as an mRNA of approximately 1,100
      nucleotides. A 41.2-kDa polypeptide and three others predicted to be modified
      forms of Yhr076wp are detected by Western blot with a Yhr076wp-specific antibody.
      Promoter activity assays indicate that YHR076w transcription is regulated by
      carbon source and primarily by ethanol. Consistent with this observation, we have
      identified two potential ADR1 regulatory elements in the YHR076w upstream DNA
      region. Potential YAP1 and HSP elements are also identified in this region,
      suggesting other forms of regulation. YHR076w knockout strains do not exhibit any
      measurable growth or morphological phenotype under any conditions tested.
      However, increased YHR076w gene dosage confers a growth advantage to both wild
      type and YHR076w knockout strains on 2% ethanol or 2% galactose medium in a low
      O2 growth environment. The fluorescence emitted by a Yhr076wp protein fusion to
      A. aquorin GFP colocalizes with the mitochondria in vivo.

PMID- 11327311
TI  - In vitro binding analysis of hepatitis B virus preS-derived putative helper T
      cell epitopes to MHC class II molecules using stable HLA-DRB1*0405/DRA*0101
      transfected cells.
AB  - In designing epitope-based vaccines, the inclusion of a helper T-lymphocyte (HTL)
      epitope is necessary to elicit both humoral and cellular immune responses.
      Whereas the preS region of the hepatitis B virus (HBV) surface antigen is well
      known to raise protective immunity, the epitopes for activating HTLs are poorly
      characterized. In an attempt to identify such epitopes, the HBV-preS region was
      screened for peptide sequences with HLA-DR4 binding motifs, and putative HTL
      candidate peptides were synthesized in a biotinylated form. Using L929 mouse
      fibroblasts stably transfected with HLA-DRB1*0405 and HLA-DRA*0101 cDNA, specific
      binding of the peptides was then detected using fluorescence-conjugated
      streptavidin. The cell-surface expression of HLA-DR molecules on transfectants
      was confirmed by confocal microscopy, and quantitative analysis of candidate
      peptide binding was performed by fluorescence activated cell sorting. Among eight
      preS-derived peptides, three candidate peptides-namely preS1(23-33), preS1(62
      72), and preS1(76-86)-showed good binding characteristics to HLA-DR4 molecules,
      among which the preS1(23-33) epitope was regarded as the most promising HTL
      epitope. Further studies with these candidate HTL stimulatory peptides will show
      their ability to activate the human immune system against HBV.

PMID- 11327312
TI  - Interaction of bacterial flagellum filaments with skeletal muscle myosin.
AB  - Interaction of isolated bacterial flagellum filaments (BFF) and intact flagella
      from E. coli MS 1350 and B. brevis G.-B.p+ with rabbit skeletal myosin was
      studied. BFF were shown to coprecipitate with myosin (but not with isolated
      myosin rod) at low ionic strength, that is, under conditions of myosin
      aggregation. The data of electron microscopy indicate that filaments of intact
      bacterial flagella interact with isolated myosin heads (myosin subfragment 1,
      S1), and this interaction is fully prevented by addition of Mg2+ -ATP. Addition
      of BFF inhibited both K+ -EDTA- and Ca2+ -ATPase activity of skeletal muscle
      myosin, but had no effect on its Mg2+ -ATPase activity. Monomeric flagellin did
      not coprecipitate with myosin and had no effect on its ATPase activities. BFF
      were shown to compete with F-actin in myosin binding. It is concluded that BFF
      interact with myosin heads and affect their ATPase activity. Thus, BFF composed
      of a single protein flagellin are in many respects similar to actin filaments.
      Common origin of actin and flagellin may be a reason for this similarity.

PMID- 11327313
TI  - Aspirin ingestion impairs oral mucosal ulcer healing by inducing membrane-bound
      tumor necrosis factor-alpha release.
AB  - Among the early manifestations of impairment by nonsteroidal anti-inflammatory
      drugs in mucosal tissue repair is the enhancement in tumor necrosis factor-alpha
      (TNF-alpha). We investigated the effect of aspirin ingestion on the processing of
      TNF-alpha in rat soft oral tissue during buccal ulcer healing. While in the
      control group, the ulcer healed by the 10th day; only a 54.8% reduction in the
      ulcer area was attained in the presence of aspirin administration. Moreover, by
      the 10th day, the delay in ulcer healing by aspirin was manifested in a 5.6-fold
      higher rate of apoptosis and a 5.2-fold higher level of soluble TNF-alpha, yet
      the expression of membrane-bound TNF-alpha showed a 38% decline. Treatment with
      metalloprotease inhibitor, Zincov, produced dose-dependent reduction (56.9%) in
      aspirin-induced increase in the mucosal expression of soluble TNF-alpha, evoked a
      62% decrease in the rate of epithelial cell apoptosis, and led to a marked
      reversal (56.9%) in aspirin-induced delay in ulcer healing. Our findings indicate
      that the impairment in buccal ulcer healing by aspirin is a result of
      upregulation in the processing of soluble TNF-alpha from its membrane-bound
      precursor that leads to the amplification of apoptotic events and potentiation of
      the mucosal inflammatory responses that interfere with healing process.

PMID- 11327314
TI  - Oligomeric structure of bAE3 protein.
AB  - The "brain" form of the anion exchanger protein 3 (bAE3) has been purified to
      homogeneity from the rabbit kidney by differential centrifugation and
      immunoaffinity chromatography. A single protein band of approximately 165 kDa was
      detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE)
      and Western blotting. Monomers, dimers (a major component), and a higher
      oligomeric form (apparently tetramers) were found after oxidative cross-linking
      of purified bAE3. The largest form of bAE3 was separated from dimers and monomers
      by sucrose gradient centrifugation and was studied by transmission electron
      microscopy to confirm a tetrameric structure. Two main types of bAE3 images were
      detected, round (approximately 11-14 nm) and square-shaped (approximately 12 x 12
      nm). Image analysis revealed fourfold rotational symmetry of both the round and
      square-shaped images, indicating that bAE3 consists of multiples of 4 subunits.
      We conclude that bAE3 in Triton X-100 solution is predominantly a mixture of
      dimers and tetramers with a smaller amount of monomers.

PMID- 11327315
TI  - Serendipity: how the concept of inborn lysosomal disease was discovered.

PMID- 11327317
TI  - Mitochondrial production of hydrogen peroxide regulation by nitric oxide and the
      role of ubisemiquinone.
AB  - Mitochondria are considered the major cellular site for hydrogen peroxide
      production, a process that is kinetically controlled by the availability of
      oxygen and nitric oxide to cytochrome oxidase and of ADP to F1-ATPase. The
      multisite regulation of mitochondrial respiration and energy-transducing pathways
      support a critical regulatory role of mitochondrion in cell signaling pathways.
      The cellular steady-state levels of hydrogen peroxide and the role of
      mitochondria in maintaining these levels are reviewed.

PMID- 11327316
TI  - An overview of oxidative stress.

PMID- 11327318
TI  - Hydrogen peroxide. Ubiquitous in cell culture and in vivo?
AB  - Hydrogen peroxide (H2O2) is widely regarded as a cytotoxic agent whose levels
      must be minimized by the action of antioxidant defence enzymes. In fact, H2O2 is
      poorly reactive in the absence of transition metal ions. Exposure of certain
      human tissues to H2O2 may be greater than is commonly supposed; levels of H2O2 in
      the human body may be controlled not only by catabolism but also by excretion,
      and H2O2 could play a role in the regulation of renal function and as an
      antibacterial agent in the urine. Cell culture is a widely used method for the
      investigation of "physiological" processes such as signal transduction and
      regulation of gene expression, but chemical reactions involving cell culture
      media are rarely considered. Addition of reducing agents to commonly used cell
      culture media can lead to generation of substantial amounts of H2O2. Some or all
      of the reported effects of ascorbic acid and polyphenolic compounds (e.g.,
      quercetin, catechin, epigallocatechin, epigallocatechin gallate) on cells in
      culture may be due to H2O2 generation by interaction of these compounds with cell
      culture media.

PMID- 11327319
TI  - Living with a killer: the effects of hypochlorous acid on mammalian cells.
AB  - The production of hypochlorous acid (HOCl) by the myeloperoxidase-H2O2-Cl- system
      of phagocytes plays a vital role in the ability of these cells to kill a wide
      range of pathogens. However, the generation of a potent oxidant is not without
      risk to the host, and there is evidence that HOCl contributes to the tissue
      injury associated with inflammation. In this review, we discuss the biological
      reactivity of HOCl, and detail what is known of how it interacts with mammalian
      cells. The outcome of exposure is dependent on the dose of oxidant, with higher
      doses causing necrosis, and apoptosis or growth arrest occurring with lower
      amounts. Glutathione (GSH) and protein thiols are easily oxidized, and are
      preferred targets with low, sublethal amounts of HOCl. Thiol enzymes vary in
      their sensitivity to HOCl, with glyceraldehyde-3-phosphate dehydrogenase being
      most susceptible. Indeed, loss of activity occurred before GSH oxidation. The
      products of these reactions and the ability of cells to regenerate oxidized
      thiols are discussed. Recent reports have indicated that HOCl can activate cell
      signaling pathways, and these studies may provide important information on the
      role of this oxidant in inflammation.

PMID- 11327320
TI  - The NADPH oxidase of endothelial cells.
AB  - The best known NADPH oxidase is that of phagocytes-neutrophils and monocytes. In
      these cells, the enzyme manufactures large quantities of O2- and other reactive
      oxidants that are used for the purpose of killing invading microorganisms. Recent
      studies, however, have suggested that a number of other tissues contain NADPH
      oxidases. In contrast to the very vigorous production of oxidants by phagocytes,
      rates of oxidant production by these other cell types are quite low. Oxidant
      production by these cells is generally thought to serve a signaling function.

PMID- 11327321
TI  - Free radicals in exhaustive physical exercise: mechanism of production, and
      protection by antioxidants.
AB  - Moderate exercise is a healthy practice. However, exhaustive exercise generates
      free radicals. This can be evidenced by increases in lipid peroxidation,
      glutathione oxidation, and oxidative protein damage. It is well known that
      activity of cytosolic enzymes in blood plasma is increased after exhaustive
      exercise. This may be taken as a sign of damage to muscle cells. The degree of
      oxidative stress and of muscle damage does not depend on the absolute intensity
      of exercise but on the degree of exhaustion of the person who performs exercise.
      Training partially prevents free radical-formation in exhaustive exercise.
      Treatment with antioxidants such as vitamins C or E protects in part against free
      radical-mediated damage in exercise. Xanthine oxidase is involved in free-radical
      formation in exercise in humans and inhibition of this enzyme with allopurinol
      decreases oxidative stress and muscle damage associated with exhaustive exercise.
      Knowledge of the mechanism of free-radical formation in exercise is important
      because it will be useful to prevent oxidative stress and damage associated with
      exhaustive physical activity.

PMID- 11327322
TI  - Oxidative stress, antioxidant defenses, and damage removal, repair, and
      replacement systems.
AB  - Oxidative stress is an unavoidable consequence of life in an oxygen-rich
      atmosphere. Oxygen radicals and other activated oxygen species are generated as
      by-products of aerobic metabolism and exposure to various natural and synthetic
      toxicants. The "Oxygen Paradox" is that oxygen is dangerous to the very life
      forms for which it has become an essential component of energy production. The
      first defense against oxygen toxicity is the sharp gradient of oxygen tension,
      seen in all mammals, from the environmental level of 20% to a tissue
      concentration of only 3-4% oxygen. These relatively low tissue levels of oxygen
      prevent most oxidative damage from ever occurring. Cells, tissues, organs, and
      organisms utilize multiple layers of antioxidant defenses and damage removal, and
      replacement or repair systems in order to cope with the remaining stress and
      damage that oxygen engenders. The enzymes comprising many of these protective
      systems are inducible under conditions of oxidative stress adaptation, in which
      the expression of over 40 mammalian genes is upregulated. Mitotic cells have the
      additional defensive ability of entering a transient growth-arrested state (in
      the first stages of adaptation) in which DNA is protected by histone proteins,
      energy is conserved by diminished expression of nonessential genes, and the
      expression of shock and stress proteins is greatly increased. Failure to fully
      cope with an oxidative stress can switch mitotic cells into a permanent growth
      arrested, senescence-like state in which they may survive for long periods. Faced
      with even more severe oxidative stress, or the declining protective enzymes and
      adaptive capacity associated with aging, cells may "sacrifice themselves" by
      apoptosis, which protects surrounding healthy tissue from further damage. Only
      under the most severe oxidative stress conditions will cells undergo a necrotic
      death, which exposes surrounding tissues to the further vicissitudes of an
      inflammatory immune response. This remarkable array of systems for defense;
      damage removal, replacement, and repair; adaptation; growth modulation; and
      apoptosis make it possible for us to enjoy life in an oxygen-rich environment.

PMID- 11327323
TI  - Focal adhesion kinase regulation by oxidative stress in different cell types.
AB  - Focal adhesion kinase (FAK) is a tyrosine kinase ubiquitously expressed in cells.
      It was initially shown to be the initiator of focal adhesion formation in
      adherent cells, after its binding to integrins which induce its
      autophosphorylation. However, it can be also activated by a great variety of
      other stimuli able to act on different intracellular signaling. Reactive oxygen
      species (ROS), which have been shown to act as external or internal cell stimuli,
      induce tyrosine phosphorylation of FAK. Its autophosphorylation is followed by a
      submembranous localization which is crucial for many of the biological roles of
      FAK, including cell spreading, cell migration, cell proliferation, and prevention
      of apoptosis. It plays an important role in development of tumor cells, its
      regulation could be thus a way of impairing cell proliferation in cancer. We
      describe in this review the structure, activity, and functions of FAK in
      different cells and how ROS are able, like other stimuli, to induce its
      phosphorylation and modification of cell morphology and structure. The link
      between ROS and FAK activation could explain the role of ROS in mediating cell
      proliferation, cell migration, or apoptosis.

PMID- 11327324
TI  - Oxidation of methionine in proteins: roles in antioxidant defense and cellular
      regulation.
AB  - The roles of methionine residues in proteins have not been well defined, but a
      review of available studies leads to the conclusion that methionine, like
      cysteine, functions as an antioxidant and as a key component of a system for
      regulation of cellular metabolism. Methionine is readily oxidized to methionine
      sulfoxide by many reactive species. The oxidation of surface exposed methionines
      thus serves to protect other functionally essential residues from oxidative
      damage. Methionine sulfoxide reductases have the potential to reduce the residue
      back to methionine, increasing the scavenging efficiency of the system.
      Reversible covalent modification of amino acids in proteins provides the
      mechanistic basis for most systems of cellular regulation. Interconversion of
      methionine and methionine sulfoxide can function to regulate the biological
      activity of proteins, through alteration in catalytic efficiency and through
      modulation of the surface hydrophobicity of the protein.

PMID- 11327325
TI  - Copper-dependent oxidative stress and neurodegeneration.
AB  - Copper is an essential trace element, but its redox reactivity leads to risks of
      damage to cell and tissues. These are well exemplified by several forms of
      neurodegenerative diseases, either arising as inherited disorders of copper
      metabolism, such as Menkes' and Wilson's disease, or as conformational diseases
      such as Alzheimer's disease and prion diseases. This review will cover some
      aspects of the involvement of copper-mediated oxidative stress in degenerative
      processes in the central nervous system, with special focus on the familial form
      of amyotrophic lateral sclerosis (FALS). Furthermore, a possible role of copper
      reactivity in inducing critical steps in the apoptotic pathways leading to
      neurodegeneration is envisaged.

PMID- 11327326
TI  - 4-Hydroxynonenal in the pathomechanisms of oxidative stress.
AB  - Here we review the current knowledge on the biochemistry and molecular pathology
      of oxidative stress with specific regard to a major aldehydic end-product
      stemming from peroxidation of biomembranes, that is 4-hydroxynonenal (HNE). This
      multifunctional molecule, which derives from the most represented class of
      polyunsaturated fatty acids in the membranes, is potentially able to undergo a
      number of reactions with proteins, phospholipids, and nucleic acids. Despite an
      active metabolism in most of the cell types, HNE can be detected in several
      biological tissues by means of sufficiently precise methods, although with
      different sensitivity. In particular, relatively high steady-state levels of HNE
      are often detectable in a large variety of human disease processes, pointing to
      some involvement of the aldehyde in their pathogenesis. Among the prominent
      pathobiochemical effects of HNE is its remarkable stimulation of fibrogenesis and
      inflammation, which indicates a potential contribution of the aldehyde to the
      pathogenesis of several chronic diseases, whose progression is indeed supported
      by inflammatory reactions and characterized by fibrosis. Further, of interest
      appears to be the ability of HNE to modulate cell proliferation through
      interference with the activity of cyclins and protein kinases and with the
      apoptotic machinery. Finally, on the basis of the already achieved evidence,
      pursuing investigation of the role of HNE in signal transduction and gene
      expression seems very promising.

PMID- 11327327
TI  - Evaluation of antioxidant capacity. What capacity is being measured by which
      method?

PMID- 11327328
TI  - LPS-induced protein oxidation and proteolysis in BV-2 microglial cells.
AB  - Exposure of proteins to oxidants leads to increased oxidation followed by
      preferential degradation by the proteasomal system. The role of the biological
      oxidant production in microglial BV-2 cells in the oxidation and turnover of
      endogenous proteins was measured. It could be demonstrated, that BV-2 cells are
      relatively resistant to fluxes of oxidants, but nevertheless protein oxidation
      occurs due to activation by LPS. This protein oxidation is followed by an
      enhanced degradation of endogenous proteins. Using PBN, a free radical scavenger
      and antioxidant, we could demonstrate the involvement of free radicals in the
      increased proteolysis in BV-2 cells after LPS-treatment. A slight but significant
      up-regulation of the proteasomal system after LPS activation takes place,
      indicating the importance of his proteolytic system in the maintenance of the
      protein pool of microglial cells.

PMID- 11327329
TI  - Endothelial dysfunction in human coronary circulation: relevance of the L
      arginine-NO pathway.

PMID- 11327330
TI  - Alcohol and the risk of myocardial infarction.
AB  - Epidemiological studies have repeatedly demonstrated a beneficial effect of
      moderate alcohol consumption on the incidence of coronary heart disease,
      myocardial infarction and overall mortality. The latter increases with excessive
      alcohol consumption. Although most epidemiological studies demonstrate a
      beneficial effect of alcohol consumption independent from the specific kind of
      alcoholic beverage, there is increasing evidence that wine and in particular red
      wine might contain pharmacological substances, which prevent atherosclerosis and
      myocardial infarction independent from the wine ethanol. Pathophysiological
      mechanisms mediating these beneficial effects include effects of wine phenols and
      tannins on LDL-cholesterol oxidation status, thrombocyte aggregation, endothelial
      function and smooth muscle cell proliferation. Identification and
      characterization of the pharmacologically active substances might provide the
      stage for the development of new substances to be used in the prevention of
      coronary artery disease and myocardial infarction.

PMID- 11327331
TI  - ERK and p38 MAP kinase activation are components of opioid-induced delayed
      cardioprotection.
AB  - Opioids have been previously shown to confer acute and delayed cardioprotection
      against a prolonged ischemic insult. We have extensively characterized the signal
      transduction pathway mediating acute cardioprotection and have suggested a role
      for extracellular signal regulated kinase (ERK) in this cardioprotection.
      Therefore, we attempted to determine a role for ERK and the stress activated MAP
      kinase, p38, in opioid-induced delayed cardioprotection by using selective
      inhibitors of these pathways. All rats were subjected to 30 min of ischemia and 2
      h of reperfusion (I/R). Control animals, injected with saline 48 h prior to I/R,
      had an infarct size/area at risk (IS/AAR) of 61.6 +/- 1.6.48-h pretreatment with
      TAN-67 (30 mg/kg), a delta1-opioid receptor agonist, maximally reduced IS/AAR
      (31.2 +/- 6.5). The involvement of ERK was examined with PD 098059, a selective
      pharmacological antagonist which inhibits the upstream kinase, MEK-1, that
      phosphorylates and activates ERK. PD 098059 (0.3 mg/kg) did not alter IS/AAR when
      administered alone (60.7 +/- 4.9). However, PD 098059 (0.3 mg/kg) administration
      30 min prior to TAN-67 (30 mg/kg) completely abolished cardioprotection (61.0 +/-
      7.6). The selective p38 inhibitor, SB 203580 (1.0 mg/kg), had no effect on IS/AAR
      in the absence of TAN-67 (53.1 +/- 2.3). Additionally, SB 203580 (1.0 mg/kg) when
      administered prior to TAN-67 (30 mg/kg) partially abolished cardioprotection
      (51.3 +/- 6.4). These results suggest that both ERK and p38 are integral
      components of opioid-induced delayed cardioprotection and may act via parallel
      pathways.

PMID- 11327332
TI  - 4-hydroxynonenal induces apoptosis, NF-kappaB-activation and formation of 8
      isoprostane in vascular smooth muscle cells.
AB  - Oxidation of lipids is considered a key feature of atherogenesis. Lipid
      peroxidation products such as oxidized LDL or the bioactive aldehyde 4
      hydroxynonenal (HNE) exert mitogenic effects on vascular smooth muscle cells
      (VSMC). These effects appear to be concentration-dependent since in addition to
      our previous reports on growth promotion at lower concentrations we here indicate
      induction of apoptosis in VSMC by 4-hydroxynonenal (HNE) at higher concentrations
      (100 micromol/L). In a line with HNE's previously documented effects on key
      mitogenic signaling elements, we also report on activation by this aldehyde of
      the redox-sensitive transcription factor NF-kappaB, a key regulator of apoptosis:
      HNE (1.0 micromol/L) induced DNA-binding of NF-kappaB in VSMC. The effect was
      inhibited by antioxidants, N-acetylcysteine and pyrrolidine dithio-carbamate. HNE
      caused phosphorylation but not degradation of the inhibitory subunit IkappaB
      alpha. HNE itself acts as an oxidant as was investigated with measurements of 8
      isoprostane which ranks among the most valuable available biomarkers of lipid
      peroxidation: HNE (1.0 micromol/L) increased 8-isoprostane levels in VSMC by 4.5
      fold (p < 0.05). Compared to the controls, plasma samples from apoEnull mice
      exhibited elevated levels of 8-isoprostane (40 pg/mL, 3.2-fold increase) and the
      combined aldehydes HNE and malonaldehyde (1.5 micromol/L, 2.5-fold increase), (p
      < 0.05, resp). In addition, immunohistochemistry indicated the presence of HNE
      protein adducts in atheroscerlotic lesions of apoEnull mice. Thus HNE is present
      in atherosclerotic tissue at concentrations that are bioactive in vitro. The data
      further indicate the involvement of the lipid peroxidation product HNE in
      atherogenesis.

PMID- 11327333
TI  - L-type calcium currents in atrial myocytes from patients with persistent and non
      persistent atrial fibrillation.
AB  - OBJECTIVE: In patients with persistent atrial fibrillation (AF), the atrial
      myocardium is characterized by a reduced contractile force, by a shortened
      duration of the action potential and a recently demonstrated reduction of the L
      type Ca2+ currents. We analyzed potential effects on L-type Ca2+ currents of the
      patients' medication and of the duration of AF. METHODS AND RESULTS: Human atrial
      myocytes were prepared from the right auricles of patients undergoing open-heart
      surgery. Three groups of patients were studied: a control group with sinus rhythm
      (SR, n = 26 patients) and a group with persistent AF (> 3 months duration; n =
      10), a group with non-persistent AF (3 patients with SR but with documented
      episodes of AF in their history). L-type Ca2+ currents were measured during
      depolarizing pulses from a holding potential of -70 mV to a test potential of +10
      mV and are given as mean +/- SEM of current densities (currents normalized to the
      cell capacitance). Ca2+ current densities were significantly (p < 0.0001) smaller
      in cells from patients with persistent AF than in control cells (0.54 +/- 0.08
      pA/pF vs. 1.96 +/- 0.12 pA/pF). No indication was found that these changes were
      caused by medication with Ca2+ channel antagonists, beta blockers, or digitalis.
      Stimulation with the dihydropyridine Bay K 8644 (1 microM) or with isoproterenol
      (0.1 microM) increased Ca2+ currents in control cells 3.5 +/- 0.2 and 3.5 +/- 0.3
      fold. In persistent AF, this increase was significantly larger (6.0 +/- 0.5 and
      5.2 +/- 0.6-fold) but stimulated currents were still significantly lower than in
      control cells. Patients with non-persistent AF exhibited Ca2+ currents well
      within the control range. CONCLUSION: A reduction in Ca2+ currents, due to a
      reduction in number as well as a depression of L-type channels, is a
      characteristic and pathophysiologically important part of the myocardial
      remodeling during long-lasting atrial fibrillation. It is not present in patients
      with non-persistent AF and not caused by medication.

PMID- 11327334
TI  - Ventricular arrhythmias following coronary artery occlusion in rats: is the
      diabetic heart less or more sensitive to ischaemia?
AB  - Rhythm disorders are common complications in diabetic patients, due to their
      enhanced sensitivity to ischaemia. However, experimental studies are
      inconsistent, and both higher and lower vulnerability to injury has been
      reported. Our objectives were to compare susceptibility to ventricular
      arrhythmias in rats with prolonged duration of diabetes induced by streptozotocin
      (45 mg/kg, i.v.), utilising two different models. Following 8 weeks, either
      anaesthetised open-chest rats in vivo or isolated Langendorff-perfused hearts
      were subjected to 30 min regional zero-flow ischaemia induced by occlusion of LAD
      coronary artery. In addition, cardiac glycogenolysis and lactate production were
      measured. In open-chest rats, 90 % of the controls exhibited ventricular
      tachycardia (VT) which represented 55.4 % of total arrhythmias, whereby only 19.9
      % of arrhythmias occurred as VT in 44 % of the diabetic rats (P < 0.05 vs
      controls). Duration of VT and ventricular fibrillation (VF) was reduced from 35.5
      +/- 11.1 and 224.8 +/- 153.9 s in the controls to 4.8 +/- 2.5 and 2.2 +/- 0.2 s
      in the diabetics, respectively (P < 0.05). Accordingly, severity of arrhythmias
      (arrhythmia score, AS) was also lower in the diabetics (2.0 +/- 0.38 vs 3.3 +/-
      0.3 in the controls; P < 0.05). In the isolated hearts, high incidence of VF was
      decreased in the diabetic hearts, and although VT occurred in almost all of the
      diabetic hearts, the duration of VT and VF was substantially shorter (61.5 +/-
      14.5 and 5.5 +/- 0.5 s vs 221.5 +/- 37 and 398.5 +/- 55 s in the controls,
      respectively; P < 0.05). AS was reduced to 2.9 +/- 0.12 from 4.1 +/- 0.3 in the
      controls (P < 0.05). Postischaemic accumulation of lactate was lower in the
      diabetic than in the non-diabetic myocardium (20.4 +/- 1.9 vs 29.5 +/- 2.9
      micromol/l/g w.wt.; P < 0.05). These results suggest that rat hearts with chronic
      diabetes, despite some differences in the arrhythmia profiles between the in vivo
      model and isolated heart preparation, are less sensitive to ischaemic injury and
      exhibit lower susceptibility to ventricular arrhythmias and reduced accumulation
      ofglycolytic metabolites.

PMID- 11327335
TI  - In vivo recording of monophasic action potentials in awake dogs--new applications
      for experimental electrophysiology.
AB  - INTRODUCTION: Despite enormous developments in the field of clinical and
      experimental electrophysiology there is still a gap in evaluating repolarization
      in the awake animal. Numerous previous studies have used monophasic action
      potentials (MAP) to assess repolarization in vitro and in vivo in anesthetized
      animal models. However, an approach for recording MAP in awake dogs without
      interference of anesthesia has not yet been developed. METHODS AND RESULTS: We
      developed an experimental technique to record MAP in conscious dogs by means of
      conventional rubber introducers which were implanted into the internal jugular
      vein. In seven awake dogs, atrial as well as ventricular MAP were simultaneously
      measured without complications. Pacing thresholds were low and stable over time
      ranging from 0.2 to 4.0 mA. The MAP amplitudes ranged from 10 to 30 mV for
      ventricular and from 5 to 15 mV for atrial MAP. Continuous MAP recordings of
      stable amplitude could be made from the same endocardial site for periods of up
      to one hour. Antegrade and retrograde AV-nodal conduction properties could be
      assessed. Programmed stimulation was performed to simultaneously determine local
      refractory periods and MAP duration at cycle lengths from 500 to 200 ms.
      CONCLUSION: In awake, unsedated dogs the measurement of MAP via rubber
      introducers permits safe, long-term recording of MAP. Such recordings may be
      useful for safety pharmacological studies in evaluating cardiovascular and non
      cardiovascular drugs with regard to their effects on repolarization. In various
      canine in vivo models including in vivo models of long QT syndrome, heart failure
      or sudden cardiac death, the present technique permits electrophysiological
      measurements without interference of anesthesia.

PMID- 11327336
TI  - Effects of propafenone on anisotropic conduction properties within the three
      dimensional structure of the canine ventricular wall.
AB  - BACKGROUND: Structural complexities of the intact ventricular wall cause a very
      complex spread of activation. The effects of regional tissue damage and of
      antiarrhythmic drugs on directional differences in activation should help to
      further elucidate intramural conduction patterns. METHODS AND RESULTS: In 10
      healthy dogs and in 5 dogs with subacute anterior wall infarction, 6 parallel
      rows of 6 needle electrodes with 4 bipolar electrode pairs per needle were
      inserted into the left anterior ventricular wall. Using a computerized
      multiplexer-mapping system, the spread of activation in epi-, endo- and
      midmyocardial muscle layers and in the surviving epicardium, respectively, was
      reconstructed. Marked differences in conduction velocities relative to fiber
      orientation were evident in the surviving epicardium of infarcted hearts.
      Directional differences in conduction velocities, although less pronounced, were
      still preserved throughout the intact ventricular wall. Epicardial transverse
      conduction in intact hearts was significantly faster than transverse conduction
      in infarcted hearts (0.87 +/- 0.11 m/s vs 0.68 +/- 0.1 m/s). In normal hearts,
      propafenone (2 mg/kg) decreased conduction velocities primarily in longitudinal
      directions (-27 +/- 10%), but also moderately in transverse directions (-13 +/- 7
      %) of all muscle layers, with no significant effect on straight (-4 +/- 8 %), but
      on oblique transmural conduction (-33 +/- 18 %). In infarcted hearts propafenone
      decreased conduction particularly in longitudinal direction (-23 +/- 14 %)
      without affecting conduction transverse to the fiber orientation (+3 +/- 6%).
      CONCLUSIONS: Longitudinal intramural shortcircuits reduce directional differences
      in activation. Transmural infarction results in a loss of alternative intramural
      pathways, unmasking marked anisotropy in the surviving epicardium. Conduction
      delay in intramural pathways explains the effects of propafenone on transverse
      and oblique transmural conduction. Primarily longitudinal conduction delay
      results in reduced tissue anisotropy.

PMID- 11327337
TI  - Inhibition of rat cardiac fibroblast growth by cAMP--but not by cGMP-dependent
      protein kinase.
AB  - Cardiac fibroblasts play a critical role in the process of pathophysiological
      cardiac hypertrophy as the cell type responsible for fibrosis. Whereas many
      growth factors and hormones are thought to be involved, possible crosstalks
      between signal transduction pathways are not well defined. Therefore we
      investigated the influence of cAMP- and cGMP-dependent protein kinases (cAK, cGK)
      on platelet derived growth factor (PDGF) stimulated growth of primary cardiac
      fibroblasts from adult rats. We show here that PDGF-BB induced cell proliferation
      can be inhibited by activation of the endogenous cAK directly via the cAMP analog
      5,6-DCL-cBIMPS as well as indirectly via the cAMP-elevating receptor agonist
      prostaglandin-E1 (PGE1). In contrast, activation of the endogenous cGK-I has no
      influence on cardiac fibroblast cell growth. The strength of the proliferation
      inhibition is dependent on the time course of cAK activation, i.e., longer
      activation with the cAMP analog results in stronger proliferation inhibition. No
      significant influence of cAK or cGK-I on Akt activation or on the short-term
      activation of the MAPK cascade was observed. In contrast, 5,6-DCI-cBIMPS
      treatment of cardiac fibroblasts causes an inhibition of long-term MAPK
      phosphorylation. A prolonged PGE1-dependent cAMP signal after addition of 3
      isobutyl-1-methylxanthine (IBMX) blocks the second long-term MAPK phosphorylation
      as well. Therefore the suppression of MAPK long-term phosphorylation, four to
      eight hours after PDGF-BB stimulation, appears to play the major role in
      inhibition of cardiac fibroblast proliferation by cAK activators.

PMID- 11327338
TI  - NHE1-inhibitor cariporide prevents the transient reperfusion-induced shortening
      of the monophasic action potential after coronary ischemia in pigs.
AB  - During myocardial ischemia intracellular acid load increases as a consequence of
      anaerobic metabolism. Exchange of excessive protons for sodium via the sodium
      proton exchanger type 1 (NHE1) is supposed to cause intracellular sodium
      accumulation. The NHE1 inhibitor cariporide has been shown to inhibit ischemia
      and reperfusion-induced ventricular fibrillation (VF) but the mechanisms are not
      fully understood. During early reperfusion transient shortening of the action
      potential has been reported, which renders the heart susceptible to reentrant
      arrhythmias. In anesthetized pigs subjected to 10 min of left circumflex coronary
      artery (LCX) occlusion and reperfusion we have investigated whether NHE1 is
      involved in reperfusion-induced shortening of the monophasic action potential
      (MAP) taken with an epicardial probe over the ischemic area. In control pigs (n =
      7) a moderate decrease in the duration of the MAP at 50 % repolarization (MAPD50)
      occurred during ischemia reaching 78.8 +/- 5.0% of the pre-ischemic duration at 5
      min (p < 0.01) and 87.3 +/- 7.6 % after 10 min. An additional, transient but
      marked shortening occurred during the first 2 min of reperfusion, which fully
      recovered after 4 min. At 50 sec of reperfusion MAPD50 fell to 53.1 +/- 8.2 % of
      the pre-ischemic value corresponding to 90.1 +/- 20.2 msec of reperfusion-induced
      shortening. Cariporide, 3 mg/kg i.v. 5 min before occlusion (n = 6), totally
      prevented reperfusion-induced MAP shortening while having no effect on MAPD50
      during ischemia. In conclusion, our data suggest that the immediate, transient,
      but strong action potential shortening during early reperfusion after 10 min of
      coronary ischemia is due to the activity of the NHE1.

PMID- 11327339
TI  - Influence of mild hypothermia on myocardial contractility and circulatory
      function.
AB  - Myocardial contractility depends on temperature. We investigated the influence of
      mild hypothermia (37-31 degrees C) on isometric twitch force, sarcoplasmic
      reticulum (SR) Ca2+-content and intracellular Ca2+-transients in ventricular
      muscle strips from human and porcine myocardium, and on in vivo hemodynamic
      parameters in pigs. In vitro experiments: muscle strips from 5 nonfailing human
      and 8 pig hearts. Electrical stimulation (1 Hz), simultaneous recording of
      isometric force and rapid cooling contractures (RCCs) as an indicator of SR Ca2+
      content, or intracellular Ca2+-transients (aequorin method). In vivo experiments:
      8 pigs were monitored with Millar-Tip (left ventricle) and Swan-Ganz catheter
      (pulmonary artery). Hemodynamic parameters were assessed at baseline conditions
      (37 degrees C), and after stepwise cooling on cardiopulmonary bypass to 35, 33
      and 31 degrees C. Hypothermia increased isometric twitch force significantly by
      91 +/- 16 % in human and by 50 +/- 9 % in pig myocardium (31 vs. 37 degrees C; p
      < 0.05, respectively). RCCs or aequorin light emission did not change
      significantly. In anesthetized pigs, mild hypothermia resulted in an increase in
      hemodynamic parameters of myocardial contractility. While heart rate decreased
      from 111 +/- 3 to 73 +/- 1 min(-1), cardiac output increased from 2.4 +/- 0.1 to
      3.1 +/- 0.31/min, and stroke volume increased from 21 +/- 1 to 41 +/- 3 ml.
      +dP/dtmax increased by 25 +/- 8% (37 vs. 31 degrees C; p < 0.05 for all values).
      Systemic and pulmonary vascular resistance did not change significantly during
      cooling. Mild hypothermia exerts significant positive inotropic effects in human
      and porcine myocardium without increasing intracellular Ca2+-transients or SR
      Ca2+-content. These effects translate into improved hemodynamic parameters of
      left ventricular function.

PMID- 11327340
TI  - A man with dyspnea relieved by head tilting.

PMID- 11327341
TI  - Regular rhythm in atrial fibrillation.

PMID- 11327342
TI  - Current therapy of multiple sclerosis.
AB  - The list of medications for both immune modulation and symptomatic relief
      continues to grow. Ideally, however, drug therapy should be part of a
      multidisciplinary approach that also includes such elements as patient education
      and physical therapy.

PMID- 11327343
TI  - Complementary and alternative therapies for rheumatic disease.
AB  - Patients with rheumatic disease are turning to complementary and alternative
      therapies in growing numbers. Many of these therapies have a long history of
      apparent safety and efficacy but have not been adequately tested in controlled
      trials. To aid physicians in guiding patients' decisions, the most frequently
      used products and practices are reviewed.

PMID- 11327344
TI  - Management of pyoderma gangrenosum.
AB  - Management of pyoderma gangrenosum continues to be a therapeutic challenge, both
      because the low incidence of the disease makes it difficult to conduct large
      scale randomized studies and because pathogenic mechanisms are not yet well
      defined. The selection of drugs and dosing schedules is therefore mainly guided
      by clinical experience.

PMID- 11327345
TI  - Early diagnosis of COPD.

PMID- 11327346
TI  - Routine gas chromatographic determination of dialkylphosphate metabolites in the
      urine of workers occupationally exposed to organophosphorus insecticides.
AB  - A routine gas chromatographic (GC) method is described for the analysis of
      dialkylphosphate metabolites in the urine of workers occupationally exposed to
      organophosphorus insecticides. The procedure involves derivatizing a freeze-dried
      urine sample with pentafluorobenzyl bromide and then determining the metabolites
      using dual capillary column GC with flame photometric detection.

PMID- 11327347
TI  - Amphetamine, clobenzorex, and 4-hydroxyclobenzorex levels following multidose
      administration of clobenzorex.
AB  - Clobenzorex (Asenlix) is an anorectic drug used as part of a weight-management
      program. The drug is metabolized by the body to amphetamine, which is then
      excreted in the urine, thus causing difficulty in interpretation of amphetamine
      positive drug tests. Previous studies have shown that the parent drug and several
      metabolites are excreted in urine. Clobenzorex itself has been detected for as
      long as 29 h following administration of a single dose. However, the parent drug
      was not always detected in samples that contained amphetamine at > or =500 ng/mL,
      the administrative cutoff for a positive result. Consequently, the parent
      compound clobenzorex is not ideal for ascertaining whether the drug was the
      origin of the amphetamine. Several metabolites of clobenzorex have been shown to
      be detected for a longer period of time than the parent. One of these, a hydroxy
      metabolite, was shown to be detected for an extended period of time. In a study
      of urine samples provided following administration of a single 30-mg dose of this
      drug, 4-hydroxyclobenzorex could be detected for up to 91.5 h. More
      significantly, that study showed all samples that were positive for amphetamine
      also contained detectable amounts of 4-hydroxyclobenzorex. This metabolite proved
      to be easily detected and was typically found at higher levels than amphetamine
      in urine samples positive for amphetamine long after clobenzorex itself could no
      longer be detected. The present study analyzed samples from a controlled
      multidose administration (30 mg of clobenzorex daily for seven days) for the
      presence of 4-hydroxyclobenzorex. The analytical procedure used acid hydrolysis
      followed by liquid-liquid extraction and gas chromatographic-mass spectrometric
      analysis with monitoring of ions at m/z 125, 330, and 364 for 4
      hydroxyclobenzorex and its 3-Cl regioisomer, which was used as an internal
      standard. Peak concentrations of 4-hydroxyclobenzorex ranged from 17,786 to
      99,044 ng/mL. Most importantly, this study also found that all samples that
      contained amphetamine at > or =500 ng/mL also contained detectable amounts of
      this hydroxy metabolite (LOD 10 ng/mL), making it a valuable tool in
      differentiating use of clobenzorex from illicit amphetamine use.

PMID- 11327348
TI  - Stability of benzodiazepines in formaldehyde solutions.
AB  - Benzodiazepine-type drugs are used in the treatment of a number of pathologic
      disorders, but they may be implicated in forensic toxicology cases because of
      their abuse potential. Occasionally, it becomes necessary to measure drug levels
      following exposure to formaldehyde (postembalming or after tissue storage) if
      drug involvement was not previously suspected. Virtually no information exists on
      the decomposition of benzodiazepines in the presence of formaldehyde (the active
      ingredient in many embalming fluids), yet formaldehyde is known to be highly
      reactive, particularly with nitrogen-containing compounds. In order to evaluate
      the effects of formaldehyde on benzodiazepines, 10 benzodiazepine drugs were
      exposed to various concentrations of formaldehyde and various pH conditions (to
      simulate potential postembalming conditions), and the decomposition of each drug
      was measured by high-performance liquid chromatography over a 30-day period. The
      decomposition rates of all but one of the benzodiazepines were accelerated (to
      differing degrees) by formaldehyde as compared to controls, and this
      decomposition was in several cases both pH and formaldehyde concentration
      dependent. Thus, forensic examiners must be particularly cautious when attempting
      to determine benzodiazepine concentrations postembalming because the compound may
      have reacted with formaldehyde to form other products not inherently obvious
      analytically. Determination of these reaction products will serve to provide
      alternate analytes, allowing for establishment of accurate conclusions during
      forensic analyses.

PMID- 11327349
TI  - Positive predictive values of abused drug immunoassays on the Beckman Synchron in
      a veteran population.
AB  - The pressure to reduce the cost of analytic testing makes it tempting to
      discontinue routine confirmation of urine specimens positive for drugs of abuse
      by immunoassay. Beyond the economic motivation, the requirement for confirmation
      should be driven by the positive predictive value of the screening tests. We have
      quantitated positive predictive values of our screening immunoassays in a large
      metropolitan Veterans Affairs Medical Center. We reviewed the confirmatory rate
      of urine specimens positive for drugs of abuse with Beckman Synchron reagents
      from June 1998 to June 1999 and tabulated the false-positive screening rate.
      There were 175 instances of false-positive screens during the 13 months we
      analyzed. Positive predictive values ranged from 0% (amphetamine) to 100% (THC).
      We determined that the low positive predictive value of the amphetamine assay in
      our laboratory was primarily due to the use of ranitidine (Zantac). Urine
      specimens containing greater than 43 microg/mL ranitidine were positive in our
      amphetamine assay. This concentration is routinely exceeded in our patients
      taking ranitidine. In our clinical and analytic setting, the Beckman THC assay
      did not require confirmation. The positive predictive values of the Beckman
      opiate, cocaine, barbiturate, propoxyphene, and methadone immunoassays dictate
      routine confirmatory testing in specimens that screen positive for these
      substances. Finally, because of its extreme sensitivity to ranitidine, the
      Beckman amphetamine assay has little utility in our laboratory setting.

PMID- 11327350
TI  - Isotopic analogues as internal standards for quantitative analyses of drugs and
      metabolites by GC-MS--nonlinear calibration approaches.
AB  - In order to achieve accurate quantitation of drugs and metabolites (analytes) in
      complex matrices, 2H- (and less commonly 13C-) labeled analogues of the analytes
      are now routinely adapted as the internal standards (IS) using linear calibration
      models to fit data generated by selected ion monitoring gas chromatography-mass
      spectrometry (GC-MS) protocols. In this study, the effects of cross-contribution
      (contribution of the IS to the intensity of the ion designated for the analyte
      and vice versa) on the linearity of the calibration data are examined. Nonlinear
      approaches that may address this problem are also studied. Two ion pairs (one
      with least and one with significant cross-contribution) from each of the
      following analyte/IS pairs are used as the exemplar systems for this study:
      butalbital/13C4-butalbital, butalbital/2H5-butalbital, secobarbital/13C4
      secobarbital, and secobarbital/2H5-secobarbital. Analyte/IS ion intensity ratios
      of a series of standard solutions are correlated with the analyte/IS
      concentration ratios using one-point, multiple-point (unweighted and weighted)
      linear, and hyperbolic functions. The one-point calibration approach produces
      excellent calibration results in treating data derived from ion pairs with no
      significant cross contribution. In cases where significant cross-contribution
      exists, results derived from the one-point approach show, as expected,
      significant deviations at both ends of the concentration range. With the cross
      contribution phenomenon accounted for, the hyperbolic calibration model is
      clearly more effective in fitting calibration data at both the lower and higher
      analyte concentration ends, thus significantly lowering the detection limit and
      extending the calibration range to a higher level. However, the calibration range
      cannot be extended indefinitely. At the low concentration end, noise-to-signal
      ratio and the cross-contribution of the IS to the intensity of the ion designated
      for the analyte, however insignificant, will incrementally reduce the quality of
      the observed ion intensity and intensity ratio data. At the high concentration
      end, detection saturation and the cross-contribution of the analyte to the
      intensity of the ion designated for the IS, however insignificant, will
      incrementally decrease the "slope" of the calibration curve. Thus, acceptable
      sensitivity (increase in analyte/IS ion-pair intensity ratio per unit increase in
      analyte concentration) of the calibration curve will become the limiting factor.

PMID- 11327351
TI  - Evaluation of immunoassays for semiquantitative detection of cocaine and
      metabolites or heroin and metabolites in extracts of sweat patches.
AB  - Two types of immunoassays, radioimmunoassay (RIA) and microplate enzyme
      immunoassay (EIA), were compared for their ability to detect and quantitate
      cocaine and metabolites or heroin and metabolites in extracts of sweat patches.
      Experiments used sweat patches that had been fortified with cocaine,
      benzoylecgonine (BE), and ecgonine methyl ester (EME) or 6-acetylmorphine (6-AM),
      heroin, and morphine. Assays were first evaluated for sensitivity in detection of
      the analyte(s) known to be excreted in sweat (cocaine >> BE and EME; 6-AM >
      heroin > morphine). The cocaine metabolite RIA had cross-reactivity for cocaine >
      BE > EME, and the cocaine metabolite EIA had cross-reactivity for BE > cocaine >>
      EME. The RIA, having greater sensitivity for COC, was studied further. Optimal
      linearity was 4 to 200 ng/patch, and quantitation within these limits at 4, 75,
      and 150 ng/patch had intrarun %CVs within 7.8% and percent targets within 15% and
      inter-run %CVs within 13.5% and % targets within 13%. The opiate RIA had cross
      reactivities for morphine >> 6-AM and heroin. The opiate EIA had cross
      reactivities for 6-AM and heroin of 42 and 28% relative to morphine,
      respectively. The EIA, having greater sensitivity for 6-AM and heroin, was
      studied further. The limits of detection ranged from 1.7 to 24.7 ng/patch, and
      the lower limits of quantitation ranged from 7.3 ng/patch to beyond the linear
      range. The assay, however, had consistently good precision at 4 and 5 ng/patch,
      and optimal linearity was established from 4 to 100 ng/patch. With controls at 5,
      25, and 90 ng/patch, both intrarun and inter-run precision were acceptable.
      Quantitation was accurate at 5 and 25 ng/patch, but the 90 ng/patch controls were
      consistently < 70% of target. Because our studies focused on the assays that had
      greater sensitivity for the analytes excreted in sweat, we did not fully evaluate
      the cocaine metabolite EIA or the RIA opiate screen and therefore cannot make any
      comment on the usefulness of these assays for detecting analytes in extracts of
      sweat patches beyond predicting that they will have less sensitivity. Both the
      cocaine metabolite RIA and opiate EIA had the ability to detect analytes known to
      be extracted from sweat patches.

PMID- 11327352
TI  - Analysis of paracetamol using solid-phase extraction, deuterated internal
      standards, and gas chromatography-mass spectrometry.
AB  - A rapid method for determining paracetamol (acetaminophen) in whole blood and
      liver tissue samples is described. Blank plus single-point calibration gives
      reliable quantitation at therapeutic and higher concentrations. Whole blood and
      liver tissue samples containing a deuterated internal standard were extracted
      using Bond Elut Certify columns. Butyl derivatives were formed using n-iodobutane
      and tetramethyl ammonium hydroxide under mild conditions and were extracted into
      ethyl acetate as a cleanup step. Recovery was better than 90%, and sample
      preparation time was less than 2 h. Gas chromatograph run time was less than 20
      min. SIM of two ion pairs formed by electron impact ionization resulted in
      intraday coefficients of variation (CV) less than 3.03% (7.48% in liver) and
      interday CVs less than 8.93% (for midtherapeutic concentrations in whole blood).
      Linearity was observed from subtherapeutic to high, fatal levels. This method has
      been applied to forensic cases and has significantly reduced analytical time
      while improving casework quality. Results of a case study involving paracetamol
      are given.

PMID- 11327353
TI  - Qualitative screening for drugs of abuse in hair using GC-MS.
AB  - A previously described method for the analysis of hair has been modified to
      include analysis for amphetamines, benzodiazepines, cocaine and its metabolites,
      methadone and its metabolite, and phencyclidine in addition to opiates on a
      sample of hair. The samples of hair were washed twice with dichloromethane and
      cut into 1-mm segments prior to extraction with methanol at 45 degrees C for 18
      h. The extracts were split into two parts; both were evaporated to dryness. One
      half of the extract was derivatized using MBTFA for analysis of amphetamines, and
      the other half was derivatized using MTBSTFA for analysis of the remaining drugs.
      The extracts were analyzed using electron impact gas chromatography-mass
      spectrometry operating in selected ion monitoring mode. In total, 18 drugs of
      abuse/metabolites could be detected. The method was used to screen 20 hair
      samples from patients attending a methadone-maintenance clinic.

PMID- 11327354
TI  - Semiautomated high-performance liquid chromatographic method for the
      determination of benzodiazepines in whole blood.
AB  - A semiautomated method for the determination of five frequently prescribed
      benzodiazepines (BZD) (clonazepam, diazepam, flunitrazepam, midazolam, and
      oxazepam) in whole blood samples by reversed-phase high-performance liquid
      chromatography following simple online enrichment and clean-up on a short
      precolumn is described. After precipitation of protein and red cells with a
      mixture of organic solvents (methanol/acetonitrile, 50:50), the aliquot is
      centrifuged and the organic upper phase evaporated under a gentle stream of
      nitrogen. The residue is reconstituted by adding 500 microL of a mixture of
      phosphate buffer (20mM, pH 2.2) and acetonitrile (70:30, v/v). The sample is then
      directly introduced into the column-switching column. The precolumn is first
      washed with phosphate buffer at pH 7.2. Compounds retained on the precolumn are
      then eluted in the back-flush mode and separated on a C8 semi-microcolumn
      (Lichrospher select B, 125 x 3 mm). The BZD studied are determined by a diode
      array detector at 254 nm. The method shows excellent linearity between 25 and
      1,000 ng/mL for clonazepam, flunitrazepam, and midazolam and between 25 and 5,000
      ng/mL for diazepam and oxazepam. The recoveries are around 80% for clonazepam and
      oxazepam and around 90% for the three others. Coefficients of variation for
      between-day and within-day assays are < 15% for low concentrations close to the
      limit of quantitation and < 5% for high concentrations.

PMID- 11327355
TI  - Concentration verification of ethanol/nitrogen compressed gas cylinders prior to
      use for periodic determinations of accuracy in California.
AB  - A method that uses compressed gas ethanol breath standard (EBS) cylinders to
      perform periodic determinations of accuracy on evidential breath alcohol
      instruments in California was developed. To use EBS cylinders, the California
      State Department of Health Services required verification of the ethanol content
      of the EBS cylinders using an infrared method. The infrared method developed
      employs a modified Alcotest 7110 MK III-C manufactured by National Draeger, Inc.
      that functions at the 9.5-mm wavelength of the infrared spectrum. Criteria and
      methodology for verifying EBS cylinder ethanol concentrations are described.

PMID- 11327356
TI  - Ecgonine is an important marker for cocaine use in inadequately preserved
      specimens.

PMID- 11327357
TI  - Radiographic findings of canine dysautonomia in twenty-four dogs.
AB  - Canine dysautonomia is an idiopathic condition resulting in loss of autonomic
      nervous system function. Recently, the prevalence of dogs diagnosed with
      dysautonomia in the mid-western United States has increased. In this study the
      medical records and radiographic findings in 24 dogs with dysautonomia were
      reviewed. A diagnosis of dysautonomia was made in 17 (71%) of the dogs in this
      study by postmortem examination, the remaining 7 (29%) dogs were diagnosed
      pharmacologically. The radiographic findings supportive of dysautonomia include
      aspiration pneumonia, megaesophagus, or a distended stomach, small bowel, or
      urinary bladder. In some instances, the disease radiographically mimicked other
      disorders of the gastrointestinal tract, including mechanical obstruction.

PMID- 11327358
TI  - The correlation of canine patellar luxation and the anteversion angle as measured
      using magnetic resonance images.
AB  - Measurements from magnetic resonance (MR) images can be used to examine the
      anteversion angle (AT-angle) and its influence on the lateromedial or
      mediolateral luxating forces on the patella. The AT-angle of the femoral neck was
      measured with the aid of MR imaging in 45 pelvic limbs without patellar
      instability, in 33 limbs with patellar luxation and in 6 limbs with rupture of
      the cranial cruciate ligament. The limbs with medial patellar luxation were
      divided into three groups based on clinical examination. The mean (range) AT
      angle was 7.6 degrees (0 degrees to 24 degrees) in the "normal" group, 8.6
      degrees (-10 degrees to 29 degrees) in the group "grade II," and -0.4 degrees in
      the group "grade III" (-28 degrees to 12 degrees). A mean (range) AT-angle of 4.8
      (-4 degrees to 11 degrees) was measured in the pelvic limbs with rupture of the
      cranial cruciate ligament. Compared to literature that described AT-angles based
      on radiographs of normal limbs, reduced AT-angles were found in this study due to
      different lines of measurement of the femoral neck. This study documents that the
      AT-angle of the femoral neck does not influence patellar instability. This study
      also demonstrates that MR images can be used to make exact measurements of the
      canine AT-angle that represent the true anatomy of the femoral neck.

PMID- 11327359
TI  - Radiographic and computed tomographic changes and clinical presentation of
      spirocercosis in the dog.
AB  - A retrospective study of 39 dogs with spirocercosis is described, emphasizing
      radiographic and computed tomographic aspects and clinical presentation. Dogs
      were classified as complicated or uncomplicated, both clinically and
      radiographically. Besides the expected upper gastrointestinal signs, a high
      incidence of respiratory (77%) and locomotor (23%) complications were present.
      All dogs had thoracic radiographs. Esophageal masses were radiographically
      classified as typical or atypical according to their location. Twenty-seven dogs
      had a typical caudal esophageal mass. Six dogs had a mass atypically located in
      the hilar region. These masses were smaller and more difficult to visualize
      radiographically. The remaining 6 dogs did not have a radiographically detectable
      esophageal mass. Radiology as an initial diagnostic tool was effective in
      detecting and localizing the mass and to detect early respiratory abnormalities
      such as pleuritis, mediastinitis, pneumonia, and bronchial displacement.
      Endoscopy was the modality of choice to confirm antemortem esophageal masses. In
      dogs where the mass filled the whole esophageal lumen, endoscopy failed to give
      essential information necessary for surgical excision of neoplastic masses, such
      as the extent of esophageal wall attachment. Caudal esophageal sphincter
      involvement was difficult to determine endoscopically with large caudal
      esophageal masses. Computed tomography was performed on 3 dogs and did not
      address the latter problems completely, but was found to be a sensitive tool to
      detect focal aortic mineralization and early spondylitis, both typical for the
      disease, and essential in the diagnosis of non- or extramural esophageal
      abnormalities.

PMID- 11327360
TI  - Mensuration of the normal pituitary gland from magnetic resonance images in 96
      dogs.
AB  - The pituitary gland was measured from transverse magnetic resonance T1-weighted
      images after Gadolinium administration in 96 dogs weighing from 13 to 45 kg. The
      measurements were done by hand with calipers. The mean (+/- standard deviation)
      pituitary gland height was 5.1 mm (+/-0.9 mm). The mean width was 6.4 mm (+/- 1.1
      mm). The correlation coefficient between pituitary and brain measurements,
      between pituitary measurement and body weight, and brain measurements and body
      weight was 0.0 to 0.3. A hyperintense region was present on T1-weighted images in
      the center of the pituitary gland in 64% of the dogs. At necropsy the pituitary
      glands were grossly and histologically normal. No pituitary gland measurements
      were performed at necropsy.

PMID- 11327361
TI  - Radiography of the thoraco-abdominal cavity of the ostrich (Struthio camelus).
AB  - A standard radiographic procedure was developed for the thoraco-abdominal cavity
      of female nonbreeding ostriches. Positioning, collimation, centering and a
      technique chart were defined to give reproducible and consistently good quality
      radiographs. Radiographs were obtained from one adult ostrich cadaver, two adult
      female ostriches as well as two growing ostriches at various stages. A 6-frame
      technique was established for lateral views taking the topographic tissue
      distribution into consideration and using easily palpable landmarks as centering
      points. Standing true right lateral radiographs are recommended for standard
      procedures. For dorsoventral exposures a 3-frame technique in the recumbent
      ostrich was found to be optimal. Birds should be fasted if possible. A technique
      chart for lateral exposures is provided.

PMID- 11327362
TI  - Asymptomatic radiographic disappearance of calcified intervertebral disc material
      in the Dachshund.
AB  - The occurrence of asymptomatic disappearance of intervertebral disc calcification
      was evaluated in a radiographic prospective longitudinal study of 40 Dachshunds
      followed from 6 or 12 months of age to 2 years of age. Radiographic follow-up was
      performed at 3 to 4 years of age in 12 dogs. Disappearance of calcified disc
      material was observed in 9 thoracic and 1 lumbar intervertebral discs. The crude
      incidence rate tended to increase with age from 1 year of age. The features of
      the disappearing calcifications involved indicate that the phenomenon is part of
      the progressive degenerative process. A possible pathogenesis includes tearing of
      the annulus fibrosus due to the severe degeneration of the disc, followed by an
      inflammatory response to nuclear material and phagocytic resorption of calcified
      material.

PMID- 11327363
TI  - Ultrasonographic evaluation of gallbladder wall thickness in cats.
AB  - Ultrasonography of the gallbladder and biliary tract was performed on 42 cats: 22
      clinically healthy cats (group A) and 20 cats with hepatobiliary disease and post
      mortem confirmation of gallbladder abnormalities (group B). The gallbladder wall
      was visible in 9 of 22 cats in group A and all 20 cats in group B. Additional
      gallbladder findings in group B included shape anomalies, biliary tract
      obstruction, wall thickening, polyps, neoplasia, and biliary sludge.
      Ultrasonographic evaluation of abdominal organs identified pancreatic disease as
      the predominant pathological cause of extrahepatic biliary obstruction. Hepatic
      parenchymal involvement was noted with inflammation and thickening of the
      gallbladder wall. Histologically, gallbladder walls were characterized by mucous
      gland hyperplasia, inflammation, infiltration, edema, epithelial detachment,
      and/or neoplasia. Ultrasonographic and histologic gallbladder wall measurements
      of 20 cats in group B agreed within 0.4 mm and all cats with a gallbladder wall
      thickness > or =1.0 mm had histopathologic abnormalities of the wall. Serum
      biochemical analysis revealed elevations of one or more parameters in all cats of
      group B, but was non-specific for a gallbladder lesion. The results of this study
      indicate that a visible, echogenic gallbladder wall can be considered a normal
      variant and is not always associated with hepatobiliary disease. Ultrasonography
      is accurate in measuring gallbladder wall thickness. Wall thickness greater than
      1 mm is accurate in predicting gallbladder disease in cats, while a thickness
      less than 1 mm cannot rule out mild or chronic inflammation.

PMID- 11327364
TI  - Ultrasonographic appearance of intra-abdominal granuloma secondary to retained
      surgical sponge.
AB  - This report describes two animals (one dog and one cat) with a retained surgical
      sponge. Both had nonspecific clinical signs. Clinical examination,
      ultrasonography and cytologic examination were used to identify an abdominal mass
      compatible with a granuloma. The lesions were surgically removed and confirmed
      histologically as granulomas secondary to a retained sponge. The ultrasonographic
      appearance was very similar in both animals.

PMID- 11327365
TI  - Evaluation of heart time-activity curves as a predictor of hepatic extraction of
      99mTc-mebrofenin in dogs.
AB  - In this study, heart time-activity curve, created following intravenous injection
      of 99mTc-mebrofenin were used to quantify hepatic function in normal dogs and
      dogs with induced hepatic parenchymal cell damage. The results were compared to a
      direct measurement of hepatic extraction following mesenteric venous injection of
      99mTc-mebrofenin. The heart time-activity curves were normalized and the area
      under the curve from 0-30 minutes and 0-60 minutes were determined. In addition,
      the half-time clearance rate of the heart time-activity curve was analyzed using
      a two-compartment model. Linear regression analysis was used to describe the
      relationship between the area under the normalized heart time-activity curve and
      hepatic extraction. There was good correlation between the area under the
      normalized heart time-activity curve and hepatic extraction. The best correlation
      was obtained from the 0-30 minute data (r2 = 0.92). A formula for calculating
      hepatic extraction was derived using linear regression analysis: Hepatic
      extraction = 1.092 - (0.0000308 x AUC0-30 minutes). There was good correlation
      between the half-time clearance rates from the heart time-activity curve and
      hepatic extraction. The best correlation was between the fast phase half-time
      clearance and hepatic extraction (r2 = 0.88). The area under a normalized heart
      time-activity curve can be used as a simple alternative to deconvolutional
      analysis for the determination of hepatic extraction as a measure of hepatic
      parenchymal cell function in the dog.

PMID- 11327366
TI  - Radiographs from the 2000 radiation oncology certifying examination: clinical
      aspects of radiation oncology, including image interpretation.

PMID- 11327367
TI  - Radiographs from the 2000 American College of Veterinary Radiology certifying
      examination: thorax section.

PMID- 11327368
TI  - Normal duplex Doppler waveforms of major abdominal blood vessels in dogs: a
      review.
AB  - The normal flow velocity profile and duplex Doppler waveform of the major
      abdominal blood vessels (aorta, caudal vena cava and the portal vein as well as
      their major branches) were examined by Doppler ultrasound. The flow velocity
      profile of an artery is largely determined by its diameter. The pulsatility of
      the waveform is related to the vascular impedance downstream to the point of
      measurement. Early systolic peak is present in the Doppler pattern of some
      vessels in some dogs. The waveform of the veins is mainly affected by the
      pressure conditions of the right atrium and the intrathoracic and intraabdominal
      pressure changes due to the respiration. Simultaneous electrocardiogram was used
      to reveal the effect of the heart beats on the Doppler patterns of the veins.

PMID- 11327369
TI  - Role of inhibins in childhood and puberty.
AB  - Inhibins, produced mainly in the gonads, suppress FSH synthesis. The bioactive
      dimeric forms of inhibin (A and B) have been proposed as peripheral markers of
      Sertoli and granulosa cell function. The determination of serum dimeric inhibins
      from birth through adulthood reflects a distinct pattern of both inhibins in
      males and females. Concomitantly with the gonadotrophin surge, an important
      production of inhibin B is observed during the first months of life. In males,
      inhibin B levels are higher than in females and persist elevated up to childhood,
      whereas in females they decrease up to prepubertal levels by 6 months of age. In
      girls, high serum levels of inhibin A are observed during the first two months of
      life; thereafter, they are undetectable until puberty. An active secretion of
      inhibin B persists in both males and females in the period of maximal LHRH pulse
      generator restraint; however, the possible gonadotrophin dependence of this
      production remains controversial. At puberty, a progressive rise in serum inhibin
      B occurs concomitantly with the increased production of sex steroids in both
      males and females. A similar secretion pattern of inhibin A is observed in girls.
      This increment is mainly exerted by gonadotrophins and modulated by multiple
      paracrine/autocrine mechanisms within the ovary and the testis that regulate the
      dimerization of the inhibin subunits throughout pubertal maturation. The
      differences observed in males and females between circulating dimeric inhibins in
      relation to gonadotrophins and sex steroid concentrations from birth through
      puberty has opened a new perspective for research in human reproduction. These
      new markers may contribute to a better knowledge of the regulation of the
      hypothalamic-pituitary-gonadal axis function and the physiopathology of the
      mechanisms involved in sexual differentiation and/or fertility disorders.

PMID- 11327370
TI  - Growth hormone binding protein 2001.
AB  - The present state of knowledge about growth hormone binding proteins (GHBP) is
      reviewed, with particular emphasis on the high affinity GHBP, which represents
      the circulating ectodomain of the growth hormone receptor (GHR). GHBP is
      conserved through vertebrate evolution, is produced in many tissues (especially
      liver) by either alternative GHR mRNA splicing (rodents) or by proteolytic
      cleavage from the GHR (humans, rabbits and several other species). The
      metalloprotease TACE (tumor necrosis factor-alpha converting enzyme) is the
      likely enzyme responsible for cleavage, but the structural requirements for TACE
      recognition or catalysis, and hence the precise cleavage point in the GHR, are
      unknown. GHBP is widely distributed in biological fluids, with marked
      concentration differences amongst them. GHBP binds about half of the circulating
      GH under basal conditions but is easily saturated at high GH levels; it subserves
      complex functions, including a circulating buffer/reservoir function for GH,
      prolongation of plasma GH half-life, competition with GHRs for GH, and probably
      unproductive heterodimer formation with the GHR. The net effect of these partly
      enhancing and partly inhibitory functions on GH action in vivo is complex and
      difficult to ascertain. Serum GHBP levels roughly parallel GHR expression
      (particularly in liver) through the life span, with very low levels in fetal
      life, upregulation to adult levels during childhood, and decline in senescence.
      Rodent pregnancy is associated with a massive increase in GHBP expression.
      Although the regulation of GHBP expression/production is not necessarily tightly
      linked to GHR expression, in general, low GHBP levels occur in conditions
      associated with GH resistance (e.g., malnutrition, uncontrolled diabetes,
      catabolic states, renal failure, hypothyroidism). Conversely, obesity, a
      condition with enhanced GH responsivity, is associated with elevated GHBP levels.
      This suggests that in many (but not all) instances of abnormal GH action, the
      GHBP level reflects GHR status. Laron syndrome (genetic GHR
      deficiency/dysfunction due to mutations in the GHR gene) is associated with low
      or undetectable GHBP in 75-80% of patients; GHBP measurement can therefore be
      used diagnostically. Depending on the design of assays for serum GH, endogenous
      GHBP may interfere to varying degrees, and GH assays should be individually
      validated and optimized in this regard. The ultimate biological role and
      physiological significance of the GHBP remain to be established.

PMID- 11327371
TI  - The promoter region of the CTLA4 gene is associated with type 1 diabetes
      mellitus.
AB  - The CTLA4 (cytotoxic T lymphocyte associated antigen-4) gene encodes the T cell
      receptor involved in the control of T cell proliferation and mediates T cell
      apoptosis. C-T polymorphism is present at position -318 from the ATG start codon
      in the promoter region of the gene. We report a study on the polymorphism in 347
      unrelated children with type 1 diabetes mellitus (DM) (age at diagnosis 7.2+/-3.8
      years) and their 260 healthy siblings as controls. Genotype C/C conferred a risk
      of type 1 DM (RR = 2.02, 95% CI 1.32-3.10, pc = 0.0033). The gene frequency of
      the C allele was higher in patients (RR = 1.91, 95% CI 1.28-2.84, pc = 0.0026).
      The gene frequency and phenotype frequency of the T allele were negatively
      associated with type 1 DM (RR = 0.52, 95% CI 0.35-0.78, pc = 0.0026 and RR =
      0.49, 95% CI 0.32-0.76, pc = 0.0022, respectively). The frequency of genotype C/T
      was lower in patients (RR = 0.50, 95% CI 0.32-0.78, pc = 0.0051). This study
      demonstrates that nucleotide -318 C-T polymorphism of the CTLA4 gene is
      associated with type 1 DM. The promoter allele -318 C confers a risk of type 1 DM
      but allele -318 T confers protection against this disease.

PMID- 11327372
TI  - Measurements of bone turnover markers in premature infants.
AB  - We determined the levels of circulating bone turnover markers in preterm infants
      during the first weeks of life. Twenty premature infants (mean gestational age
      27+/-2.2 weeks, mean birth weight 894+/-231 g) hospitalized in the neonatal
      intensive care unit (NICU) at the Meir General Hospital, Israel, participated in
      the study. Measurements of bone turnover markers were performed at birth, and
      every week thereafter for an average follow-up of 11.2+/-0.7 weeks. Bone
      osteoblastic activity was assessed by measurements of circulating osteocalcin,
      bone-specific alkaline phosphatase (BSAP) and the C-terminal procollagen peptide
      (PICP) levels. Bone resorption was assessed by measurements of serum levels of
      the carboxy-terminal cross-links telopeptide of type I collagen (ICTP). All three
      markers of osteoblastic activity increased markedly and significantly during the
      first three weeks of life, and then continued to increase gradually until week 10
      (p<0.01). Circulating ICTP levels increased in the first week of life and then
      decreased gradually throughout the follow-up (p<0.01). The study participants
      were divided into premature infants born at extremely low birth weight (ELBW:
      <1000 g, n=12) and very low birth weight (VLBW: 1000-1250 g, n=8). Osteocalcin
      (in weeks 2-5 of life), PICP (weeks 3-5), and ICTP levels (weeks 2-3) were
      significantly higher in VLBW preterms. These results suggest increased bone
      formation in premature infants in the first three months of life. The increased
      bone turnover in VLBW compared to ELBW premature infants may be the result of a
      generally higher morbidity in ELBW preterm infants in early stages of life.

PMID- 11327373
TI  - Growth response, pubertal growth and final height in Greek children with growth
      hormone (GH) deficiency on long-term GH therapy and factors affecting outcome.
AB  - The growth data of 156 children (100 boys, 56 girls) with growth hormone
      deficiency (GHD), treated with human growth hormone (GH) for 5.7+/-3.7 years,
      from 1970-1997, were retrospectively analyzed to assess the efficacy of GH
      treatment and the factors involved. 62.2% of the studied population had
      idiopathic GHD (IGHD) and 35.2% had organic GHD (OGHD). At initiation of
      treatment, chronological age (CA) was 10.1+/-4.0 years in children with IGHD and
      9.7+/-4.0 years in those with OGHD, while bone age (BA) was 7.0+/-3.7 and 7.7+/
      3.2 years, respectively. The SDS of the growth velocity during the first year of
      therapy (GV1) was negatively related to CA at start of therapy (r = -0.53, p =
      0.01). 109 children have reached final height (FH): 67 boys (FH = 165.3+/-6.3 cm)
      and 42 girls (FH = 153.9+/-5.4 cm). FH SDS was not significantly different from
      target height (TH) SDS. In the total group, FH SDS was positively related to
      height SDS for CA and BA at start of therapy (p = 0.01, p = 0.001, respectively),
      to TH SDS (r = 0.40, p = 0.001), and to GV1 (r = 0.33, p = 0.001). TH SDS was not
      different between the IGHD and OGHD groups (-1.02+/-0.8 vs. -0.94+/-6.9). The
      height gain at puberty did not differ between the groups with induced or
      spontaneous puberty in boys (23.7+/-8.6 vs. 25.4+/-6.9, not significant), while
      in girls it was higher in the group with spontaneous puberty (12.7+/-7.3 vs.
      20.0+/-9.0, p = 0.008). The age and height at start of puberty was higher in
      girls and boys with induced puberty. In the total group, the FH SDS of children
      with induced puberty was higher in comparison with those with spontaneous puberty
      (-1.0+/-0.8 vs. -1.7+/-0.9, p = 0.001) and it was positively related to the
      height at start of puberty. When the two sexes were analyzed separately, the
      difference reached significance only in boys. In conclusion, children with GHD on
      GH treatment achieved a final height which was comparable to their genetic
      potential. The FH of children with OGHD was not different from those with IGHD.
      The age and height at start of puberty were the most significant determining
      factors for FH. Hence, a better FH might be expected by delaying or arresting
      puberty.

PMID- 11327374
TI  - Persistence of delayed adrenarche in boys with thalassemia.
AB  - 5 years after a previous study, we followed up a group of thalassemic patients,
      determining DHEA-S levels in peripubertal age, with the aim of evaluating whether
      adrenarche maturation occurred in boys and advanced in girls. Furthermore, we
      evaluated the degree of bone mineral density (BMD SDS(BA)) and analyzed growth
      parameters calculating standard deviation score with respect to bone age (BA) of
      height (Ht SDS(BA)), sitting height (SH SDSBA), and subischial leg length (SLL
      SDSBA), body mass index (BMI) and the difference between the values of the
      previous and the present study (deltaBMI), thyroid function and serum markers of
      bone metabolism. Our results showed persistent lack of adrenarche (DHEA-S 25+/
      9.5 microg/dl) in all 6 boys and the absence of pubertal signs at chronological
      age (CA) of 12.4+/-1.4 yr and BA of 11.1+/-1.1 yr. Only one boy, 6 months later,
      showed a testicular volume of 4 ml (Tanner stage G2) with an increase of DHEA-S
      value (181 microg/dl) at BA 12.8 yr. Body disproportion and severe degree of
      osteopenia (BMD SDSBA -2.41+/-0.5) were observed in all boys, even though Ht
      SDSBA (0.14+/-0.8) and markers of bone metabolism were within the normal range.
      No change in nutritional status was observed (deltaBMI 0.09+/-0.4 kg/m2). In
      contrast, all the thalassemic girls had DHEA-S values (172.7+/-97.7 microg/dl)
      within the normal range at BA 12.7 +/-0.6 yr that was similar to CA. Furthermore,
      the appearance of Tanner stage B2 occurred in each of them at BA, near to CA, of
      10.4+/-0.9 yr, and menarche was observed in three of them at mean BA, near to CA,
      of 11.4+/-0.9 yr. Ht SDSBA was below normal range (-1.11+/-0.8), but SLL SDSBA
      and SH SDS(BA) values were reduced homogeneously, so that proportional body
      growth was observed. A significant change in nutritional status was observed
      (deltaBMI 2.69+/-0.9 kg/m2). Bone density value (BMD SDS(BA) -0.25+/-0.4) was in
      the normal range. There were no statistically significant differences between
      boys and girls for ferritin serum levels, blood consumption and desferrioxamine
      dosage. In conclusion, lack of change in nutritional status, measurable in the
      form of deltaBMI, but not BMI alone, considered an important physiological
      regulator of adrenarche, regardless of individual adrenal androgen secretion,
      could have a key role in the lack of adrenarche persisting in thalassemic boys
      during peripubertal age. Further follow up is necessary, in particular when boys
      reach puberty, because delayed adrenarche represents the most intriguing aspect
      in these patients.

PMID- 11327375
TI  - Adrenal nodules in patients with congenital adrenal hyperplasia due to 21
      hydroxylase deficiency: regression after adequate hormonal control.
AB  - Adrenal nodules have been described in patients with 21-hydroxylase deficiency
      (21OHD). These nodules are usually considered to be ACTH-dependent, as is the
      commonly seen diffuse cortical hyperplasia. We evaluated the presence and
      behavior of adrenal nodules in patients with 21OHD. Based upon hormonal status
      and treatment compliance, the patients were classified into three categories:
      poor, regular and good control. Out of the 26 patients, eight had the non
      classic, four salt-wasting and 14 simple virilizing forms. All patients underwent
      initial adrenal morphological studies, either by CT or MRI. Those with nodules
      were reevaluated after 12 months of adequate replacement therapy. Nodules were
      found in four of eight untreated patients and two of three patients with poor
      hormonal control, but not in the 15 patients with regular or good control.
      Adrenal nodules in these six patients demonstrated a considerable size reduction
      and even disappearance after adequate replacement therapy, showing that these
      nodules were ACTH-dependent. Thus, six out of 26 patients with 21OHD presented
      adrenal nodules, which were more frequent in the untreated or poorly-controlled
      patients, and all regressed in size after adequate therapy.

PMID- 11327376
TI  - True hermaphroditism: clinical features, genetic variants and gonadal histology.
AB  - True hermaphroditism is a rare cause of intersexuality in which both ovarian and
      testicular tissue is present in the same individual. We present the clinical
      findings, karyotype, gonadal histology and management of eight patients with true
      hermaphroditism. Their ages ranged from 43 days to 12 years at the first
      evaluation. The presenting symptoms were ambiguous genitalia (6 patients),
      isolated clitoromegaly (1 patient) and hypospadias (1 patient). The most common
      karyotype was 46,XX (6 patients). In one patient the karyotype was 46,XY and in
      another 45,XO/46,XY mosaicism, which is rare in the literature. A vagina was
      found by genitography in all patients, and at laparotomy the uterus was found
      normal in five patients, hypoplastic in one patient, as a fibrous band in one,
      and absent in the remaining patient. Histological investigation of the gonads
      revealed bilateral ovotestis in two patients, ovotestis plus ovary in two
      patients, and ovary on one side and testis on the other side in three patients.
      Five patients were assigned to the female sex, and three to the male sex. One of
      these patients was changed from male to female after evaluation.

PMID- 11327377
TI  - Serum leptin, IGF-I and insulin levels in preterm infants receiving parenteral
      nutrition during the first week of life.
AB  - Leptin is involved in the regulation of body weight through a feedback signal
      between adipose tissue and the satiety center, to decrease food intake and
      increase energy expenditure. Newborn infants experience physiological weight loss
      during the first week of life. The leptin level may be decreased to enhance food
      intake and to decrease energy expenditure for physiological adaptation during
      early postnatal days. Insulin-like growth factor-I (IGF-I) and insulin are
      involved in the regulation of perinatal growth. Leptin might be interrelated with
      IGF-I or insulin, since both of these have adipogenic and somatotropic effects.
      We therefore hypothesized that leptin, IGF-I and insulin would be decreased
      during the first week of life, concurrently with physiological weight loss.
      Thirty preterm AGA infants (birth weight 1.574+/-313 g; GA 31.9+/-2.2 wk) were
      studied. All infants received parenteral nutrition from the third day after
      birth. Leptin was significantly decreased during the first week of life, and
      insulin was significantly increased at day 7 vs. day 1 and day 3. IGF-I did not
      change during the first week of life. Leptin was positively correlated with body
      weight (r = 0.368, p<0.01), body mass index (r = 0.267, p<0.05), and serum IGF-I
      (r = 0.330, p <0.01), but not with serum insulin. The percent of weight reduction
      during the first week of life was not correlated with the percent of leptin
      reduction during the first week of life. In conclusion, leptin was significantly
      decreased and positively correlated with body weight and IGF-I during the first
      week of life. Changes of leptin and insulin might be related to postnatal
      adaptation in metabolism, but the exact role of leptin, IGF-I and insulin in
      postnatal physiological weight loss is not clear.

PMID- 11327378
TI  - Partial remission phase and metabolic control in type 1 diabetes mellitus in
      children and adolescents.
AB  - A better understanding of the remission phase, while residual beta-cell function
      is still present in recently diagnosed type 1 (insulin dependent) diabetes
      mellitus (IDDM), is very important because of the potential for pharmacological
      intervention to preserve this function. To evaluate the natural course and
      characteristics of the remission phase in children and adolescents with IDDM, a
      retrospective study was performed on patients diagnosed with IDDM under the age
      of 18 years during the years 1991-1998. Sixty-two patients whose medical records
      were available were included in the study. Data were collected by reviewing the
      hospital records of patients from the time of diagnosis through the first 24
      months after diagnosis. The duration of symptoms and history of infection prior
      to presentation, diabetic ketoacidosis (DKA) at diagnosis, length of
      hospitalization, initial glucose level, basal C-peptide levels at diagnosis,
      daily insulin requirements per kg body weight and HbA1c at diagnosis and at each
      visit were recorded. Thirty-five patients (56.5%) entered partial remission. We
      observed similar remission rates in those aged <10 and > or =10 years at
      diagnosis and in boys and girls. History of infection and presentation with DKA
      were associated with a lower rate of remission (p<0.001, p<0.0001, respectively)
      and were more commonly observed under the age of 10 years (p<0.0001, p<0.0001,
      respectively). The average insulin requirements per kg body weight calculated at
      diagnosis decreased with increasing age (r = -0.31, p = 0.012). The length of
      time until remission was 1.36+/-1.03 (mean +/- SD) months and positively
      correlated with insulin requirements at discharge from the hospital (r = 0.63,
      p<0.0001). Mean duration of remission was 11.67+/-5.82 months and was much longer
      in boys than girls (p<0.05). Six patients, all boys, entered total remission for
      3.80+/-3.73 months. HbA1c concentrations in the first year of the disease were
      significantly lower in patients who underwent a remission phase (7.31+/-1.24% vs.
      8.24+/-1.47%, p <0.05). However, this difference was not observed during the
      second year of the disease. In conclusion, history of infection prior to
      presentation and DKA at diagnosis were associated with young age and were the
      most important factors negatively influencing the remission rate in newly
      diagnosed IDDM patients.

PMID- 11327379
TI  - Natural history of asplenism in APECED--patient report.
AB  - Only a few reports on patients with hypo/ asplenism associated with APECED have
      been published, yet hyposplenism has been found in approximately half of the
      studied patients. The 7-year follow-up in our only patient with APECED revealed a
      decrease of spleen size from normal to half-size by ultrasound and CT
      examinations. Scintigraphy of the liver and spleen demonstrated a progressively
      diminishing splenic uptake of the tracer from low to complete absence. Peripheral
      blood smears revealed permanent thrombocytosis with the presence of Howell-Jolly
      bodies when functional asplenism was reached. The cause of autoimmunization and
      hyposplenism in APECED is unknown. We hypothesize that hyposplenism depends
      primarily on local AIRE gene dysfunction in the spleen, and secondarily on an
      AIRE gene-mediated autoagressive process. In our opinion, hypo/asplenism in
      APECED disease might not be noticed in patients with APECED if not directly
      examined. Thus we emphasize the necessity of searching for hyposplenism in all
      patients with APECED, and recommend scintigraphy.

PMID- 11327380
TI  - Neonatal diabetes mellitus: patient report and review of the literature.
AB  - A female infant born at 33 weeks gestation to a gestationally diabetic mother
      developed apnea and respiratory distress at 6 hours of age. Laboratory
      investigation demonstrated persistent hyperglycemia, and the patient was treated
      with continuous intravenous and subsequent subcutaneous insulin therapy. Detailed
      laboratory investigation to reveal the etiology of hyperglycemia and further
      endocrine evaluation were not significant. The baby's insulin requirement has
      continued thereafter, and she is being followed up in an outpatient clinic still
      under insulin therapy at 18 months of age. Neonatal diabetes mellitus should be
      considered in the differential diagnosis of neonatal hyperglycemia, and it may
      develop in newborns born to diabetic mothers, as well as neonatal hypoglycemia.
      Insulin treatment with close blood glucose monitoring is essential as long as
      hyperglycemia persists since neonatal diabetes mellitus may be either transient
      or permanent and it is not possible to differentiate these two outcomes before 18
      months of age.

PMID- 11327381
TI  - Shift in FTIR spectrum patterns in methomyl-exposed rat spleen cells.
AB  - Methomyl is a highly toxic carbamate insecticide which is widely used in many
      agricultural countries. We have applied the Fourier-transformed infrared (FTIR)
      spectroscopic method to study the toxicity of methomyl on cytoskeletal protein
      and the nucleic acid of rat spleen cells. Rats were given methomyl by gavage at
      2, 6 and 8 mg/kg in single doses. Colchicine, a microtubule-disrupting agent, was
      given to rats at 2, 4, and 6 mg/kg in single doses and mitomycin C, an alkylating
      agent which acts as a DNA-cross-linking agent, was given by an intraperitoneal
      route to rats at 1 mg/kg. It was shown that the wavenumber of FTIR spectra at
      amide I and amide II in both methomyl- and colchicine-exposed rats shifted in
      dose response manner when compared with the control (P < 0.05). The amide I and
      II shifts in these regions have been proposed to be the result of an alpha-helix
      protein conformational change. Toxic doses of mitomycin C, a DNA-cross-linking
      agent, did not result in this pattern. Moreover, all exposed rats showed an
      increase in the absorbance ratios that were related to the vibrational mode of
      the phosphodiester group in nucleic acid (P < 0.05).

PMID- 11327382
TI  - In vitro inhibition of thymulin production in mercury-exposed thymus of young
      mice.
AB  - Lymphocyte differentiation, maturation and peripheral functions are affected by
      the thymic protein hormone thymulin. Mercury at very low concentrations has been
      seen to impair some lymphocytic functions causing subclinical manifestations in
      exposed workers. The present study was performed to test in vitro the effect of
      mercury on the production kinetics of thymulin using cultures of whole thymuses
      from young mice. Exposure to mercury (10(-8) M and 10(-6) M) added to the
      cultures, reduced kinetic thymulin production at all time intervals considered
      (1, 2, 4, 5 and 6 h) as compared to kinetic thymulin production of thymuses from
      young control mice. After the first hour the inhibition is more evident at the
      highest mercury concentration. Thymulin production decreased by 70, 74, 82 and
      86% and by 55, 66, 73 and 81% for mercury concentrations of 10(-6) M and 10(-8)
      M, respectively, after 2, 4, 5 and 6 h. Mercury toxic effect on thymulin kinetics
      may be directly exerted to thymulin synthesis in epithelial cells, although it is
      less dramatic than that of cycloheximide (CHX), known as a potent inhibitor of
      protein synthesis in such cells. The toxic effect of mercury on thymic endocrine
      activity might cause the subclinical effects on cell-mediated immunological
      status observed in mercury exposed workers.

PMID- 11327383
TI  - Induction of the imbalance of helper T-cell functions in mice exposed to diesel
      exhaust.
AB  - Administration of diesel exhaust particles (DEP) increases antigen-specific IgE
      production and IgE-secreting cells, and induces Th2-type cytokine profiles in the
      airway in mice and humans. To determine the early effects of diesel exhaust (DE)
      inhalation on the cytokine production profile, BALB/c mice were exposed to 0
      (controls) and 1.0 mg/m3 DE inhalation for 4 weeks. Intraperitoneal sensitization
      with ovalbumin (OVA) was conducted immediately before DE inhalation. Mice were
      treated with anti-CD4 or anti-CD8 mAb 1 day before and after the sensitization.
      On day 21, these mice were boosted with OVA and blood; bronchoalveolar lavage
      (BAL) fluid, and spleens were collected on day 28. In BAL fluid, both TNFalpha
      and IL-10 production in DE-exposed and control mice remained basically the same.
      IL-6 production in the anti-CD4 treatment group of DE-exposed mice, however,
      significantly increased compared with that of the controls. In vitro antigen
      stimulated interleukin-4 (IL-4) and -10 (IL-10) production in spleen cells of
      exposed mice were not affected by low-dose DE inhalation. In vitro interferon
      (IFN)-gamma production in the anti-CD4 treated group of exposed mice decreased
      markedly. Although anti-OVA IgE production in the plasma of sham-treated mice
      exposed to DE was the same level as for controls, anti-CD4 mAb treatment in DE
      exposed mice significantly reduced IgE production compared to controls. In anti
      OVA IgG1 production, anti-CD4 or anti-CD8 mAb treatment in DE-exposed groups also
      significantly reduced. Anti-OVA IgG2a production was reduced by treatment with
      anti-CD4 mAb, but increased by anti-CD8 mAb treatment in DE-exposed mice. Low
      dose DE inhalation is thus shown to adversely affect the cytokine and antibody
      production in mice by altering CD4+ and CD8+ T-cell functions.

PMID- 11327384
TI  - Industry experience in the identification of the immunotoxic potential of
      agrochemicals.
AB  - During recent years immunotoxicity has been increasingly recognized as an
      important endpoint in rodent short-time studies. This has been documented by FDA,
      OECD, and just recently in a new EPA guideline. This guideline is confined to the
      immunosuppressive effects of chemicals. Various parameters to detect immunotoxic
      effects exist, including cell counts, cell subpopulation analysis, functional
      tests, and/or advanced pathology. Their validity in detecting immunotoxic effects
      has been demonstrated to different degrees. Our experience with some of these
      parameters is reported here. Due to the recommendation of the guideline, it is
      necessary to differentiate from the context of the study data between primary and
      secondary immunotoxicity, the latter being an unspecific sequel of toxicity to
      other organs. In our studies, we found examples for both mechanisms. For primary
      immunotoxic substances, immunosuppression is markedly more frequent than
      immunostimulation, although primary effects, on the whole, occur relatively
      seldom during toxicological screening. In both cases, we found a good correlation
      between cell analysis and functional parameters on one hand and pathology on the
      other, thus warranting that overt immunotoxicity would not remain undetected in
      routine studies with high dose levels. However, the higher predictivity of
      functional parameters and the analysis of special subpopulations is necessary for
      the determination of the no-effect level and for fine differentiation during the
      screening of comparable immunotoxic compounds. Cyclosporin A is an example for
      the former, and the screening of different agrochemicals is an example for the
      latter aspect. As verified by the collaboration studies, an advanced
      histopathology of lymphoid organs, combined with flow cytometry of immune
      competent cells and a functional assay, is able to discriminate between primary
      and secondary effects as well as immunosuppression and immunostimulation, and
      thus to identify an immunotoxic hazard.

PMID- 11327385
TI  - Effects of low frequency electromagnetic fields on expression of lymphocyte
      subsets and production of cytokines of men and women employed in a museum.
AB  - The objective of this study was to analyse the immune response to electromagnetic
      fields (ELMFs) in seven men and eight women employed in a museum. The workers
      were exposed in a room to an ELMFs (range 0.2-3.6 microT and 40-120 V/m) induced
      by 50 Hz electricity for 20 h a week. Control groups consisted of 47 women and 39
      men with a similar percentage of atopic subjects, age (range 30-51 years) and
      smoking habits of the workers included in the study. Levels of blood lead (Pb)
      and urinary trans-trans muconic acid, a metabolite of benzene (markers of
      exposure to traffic and smoking) of the control and exposed groups were similar.
      Lymphocyte subsets were determined in men and women using conjugated antibodies.
      Serum interleukin (IL) 4 and interferon gamma and their 'in vitro' production by
      peripheral mononuclear blood cells (PMBCs) stimulated by phytohemoglutinin (PHA),
      as well as blastogenesis of PMBCs induced by PHA, were determined in women only.
      ELMF-exposed women showed a significant reduction in the percentage of B and NK
      CD3(-)-CD25+ lymphocytes and a slight reduction of CD16(+)-56+ NK lymphocytes.
      They also showed significantly lower levels of interferon gamma in serum, or
      produced in the supernatants by PMBCs both spontaneously and stimulated by PHA,
      while they did not show significant changes in serum and 'in vitro' produced IL
      4, or in blastogenesis of PMBCs. Men working in the museum showed, in relation to
      the controls, a statistically significant reduction in both number and percentage
      of CD16(+)- CD56+ and CD3(-)-CD25+ lymphocyte subsets. On the whole, this
      investigation demonstrates a reduction of blood NK lymphocytes and of the
      production of interferon gamma in workers exposed to low frequency ELMFs. Recent
      studies have shown that stress and poor lifestyle induce the reduction of blood
      cytotoxic activities possibly acting on nervous functions. This may suggest that
      ELMFs reduces blood NK lymphocytes by combined effects on the immune and nervous
      systems.

PMID- 11327386
TI  - Effects of silica on human lung fibroblast in culture.
AB  - Silica has been reported to directly stimulate cellular proliferation of human
      lung fibroblasts, and silica-treated macrophage supernatants induce fibroblast
      proliferation and some of their biosynthetic activities. Alveolar macrophages
      produce increased amount of tumour necrosis factor alpha (TNF-alpha) and
      transforming growth factor beta (TGF-beta). Lung fibroblasts are producers of
      interleukin-6 (IL-6). We investigated the capacity of lung fibroblasts obtained
      from normal and silicosis subjects to elaborate IL-6 in response to TNF-alpha and
      to TGF-beta. Our data show that TNF-alpha and TGF-beta are able to stimulate the
      proliferation of human lung fibroblasts in culture, to increase the collagen
      production of the cells and are both able to increase IL-6 production by lung
      fibroblasts of patients with silicosis. We hypothesise that silica is able to
      stimulate lung fibroblast both directly, increasing the cell proliferation, and
      indirectly stimulating the release of factors (as TNF-alpha and TGF-beta) from
      activated alveolar macrophages, that are able to increase proliferative and
      biosynthetic activities of fibroblast.

PMID- 11327388
TI  - Effects of chronic exposure to anaesthetic gases on some immune parameters.
AB  - A cross-sectional survey was carried out to evaluate the relation between
      occupational exposure to low levels of anaesthetic gases (nitrous oxide and
      isoflurane) and immune parameters. Fifty-one anaesthetists were recruited among
      different Services of Anaesthesiology and Reanimation. The control group
      consisted of non-exposed physicians, similar for gender, age, and job grade.
      Total number of lymphocytes, lymphocyte subpopulations and the natural killer
      (NK) cytotoxic activity were measured. Information on personal and professional
      characteristics and on short- and long-term exposure was collected. Percentages
      of T cells (CD3) decreased significantly in anaesthetists compared to controls,
      whereas numbers of NK cells (CD16+ CD3-) increased. After correction for
      confounders, short-term (last 2 weeks) exposure was associated with a decrease in
      percentages of total T and T helper (CD4) cells. Furthermore, T helper
      percentages were significantly reduced with increasing individual exposure score
      evaluated on the basis of working days and levels of anaesthetic gases in
      operating rooms. A significant X-ray-associated increase of numbers and
      percentages of NK cells was lastly observed. Despite limited present exposure to
      anaesthetic gases, a specific derangement in lymphocyte subpopulations, with T
      lymphocytes more affected than B, has been observed.

PMID- 11327387
TI  - Autoantibodies detectable in the sera of silicosis patients. The relationship
      between the anti-topoisomerase I antibody response and HLA-DQB1*0402 allele in
      Japanese silicosis patients.
AB  - Eighty-one Japanese silicosis patients and 66 healthy volunteers were analyzed
      for autoantibodies by ELISA, and HLA-genotyping using the PCR-RFLP method was
      performed. Anti-topoisomerase I (anti-topo I) autoantibodies were detected in
      seven patients without any clinical features of autoimmune diseases such as
      progressive systemic sclerosis (PSS), although anti-topo I have been mostly
      reported in PSS patients. Antibodies directed to RNP, ssDNA, dsDNA and cent-B
      were not detected among the anti-topo I positive patients. The indirect
      immunofluorescent staining pattern of Hep-2 cells with the sera of anti-topo I
      positive silicosis patients demonstrated the typical mode of anti-topo I
      autoantibodies observed in the patients with PSS. The allelic frequency of HLA
      DQB1*0402 was significantly higher in anti-topo I positive patients (28.6%) than
      in anti-topo I negative patients (1.5%, P < 0.001) or healthy controls (0.8%,
      P<0.001). HLA-DQB1*0301, DQB1*0601 and DPB1*1801 alleles were more frequently
      detected in anti-topo I positive patients than in the patients without anti-topo
      I or in healthy volunteers, but no significant difference was observed. DQB1
      allele is associated with the induction of anti-topo I autoantibodies in Japanese
      silicosis patients, but the allele is not the same as in Caucasian PSS patients.
      Another allele (DQB1*0402) plays an important role in Japanese silicosis
      patients. The most important factor to induce anti-topo I autoantibodies seems
      not to be the type of alleles themselves, but the position of some specific amino
      acid residues in the DQ beta first domain. These findings will be useful for
      preventing occupational autoimmune diseases.

PMID- 11327389
TI  - Monocyte-macrophage system and polymorphonuclear leukocytes in workers exposed to
      low levels of metallic mercury.
AB  - Our previous research (Soleo L, Vacca A, Vimercati L et al. Occup Environ Med
      1997;54:437-442) showed a reduction in tumor necrosis factor-alpha (TNF-alpha)
      serum levels in workers with prolonged exposure to low doses of inorganic
      mercury, suggesting an in vivo functional defect of the monocyte-macrophage
      system. On this basis, here we wondered whether workers exposed to lower doses of
      metallic mercury displayed possible changes in the monocyte-macrophage system. In
      this particular cohort of workers, we also sought for the effects of the exposure
      on the polymorphonuclear leukocytes (PMNL) chemotaxis. The monocyte-macrophage
      system and the natural killer (NK) cells were examined in 19 exposed workers and
      in 25 unexposed workers, as the control group (controls). Specifically, the
      circulating monocyte-macrophage cells and their CD13, CD15 and CD33 subsets,
      serum cytokines (IL-8, GM-CSF and TNF-alpha) and the NK cells were analyzed. In
      seven exposed and seven controls randomly chosen workers the PMNL chemotaxis was
      also assessed. The selected indicator of mercury exposure were the levels of
      mercury in the urine (U-Hg), that was significantly higher in exposed workers
      than the controls (9.7 +/- 5.5 microg/l and 2.4 +/- 1.2 microg/l, respectively).
      None of the exposed workers had shown signs of either acute or chronic inorganic
      mercury toxicity or any form of hypersensitivity. Several immunological variables
      tested, monocyte-macrophage cells and their subsets, NK cells and serum cytokines
      overlapped between the exposed and the control workers. When the workers were
      considered as a whole (exposed plus controls), no correlation was found between
      current U-Hg and all immunological parameters. However, when exposed workers were
      studied separately, an inverse correlation was disclosed between cumulative U-Hg
      and cells (as percentage) expressing the CD13 (r = -0.599; P = 0.007) and CD15 (r
      = -0.614; P = 0.005) molecules, and NK cells (r = -0.455; P = 0.05). Moreover, a
      significant impairment in the PMNL chemotaxis (t = 3.70; P = 0.003) was observed
      in the exposed workers. The results of our study suggest that the exposure to
      very low levels of metallic mercury led to subtle impairment of circulating
      monocyte and NK cells (as percentages) according to the increase in U-Hg levels,
      as well as of the PMNL chemotactic function in this particular group of workers,
      even though they remain clinically asymptomatic. Therefore, we suggest that
      impairment of these parameters provide a sensitive indicator of metallic mercury
      and other chemical contaminants present in the environment.

PMID- 11327390
TI  - Evaluation of the health risk of platinum group metals emitted from automotive
      catalytic converters.
AB  - A health risk assessment of platinum (Pt) emitted from automotive catalytic
      converters is presented. Following a stepwise approach, the relevant literature
      is discussed in order to characterize Pt emissions as well as the toxic potential
      of Pt and its compounds. In an exposure assessment, ambient Pt concentrations in
      air are predicted to range from approximately 4 pg/m3 (street canyon, typical
      conditions) up to approximately 112 pg/m3 (express motorway, severe conditions).
      These values agree well with the few measured concentrations, which are also in
      the low pg/m3 range. Pt is emitted from catalytic converters in very small
      amounts (ng/km range), mainly in the (0)-oxidation state (elemental Pt). The
      nanocrystalline Pt particles are attached to microm-sized aluminum oxide
      particles. Whether free ultrafine Pt particles may be emitted and result in
      biological effects has not been studied sufficiently. Hence, risk assessment can
      only be based on the respiratory sensitizing potential of halogenated Pt salts.
      The presence of such compounds in automotive Pt emissions cannot definitely be
      excluded. From recent occupational studies conducted in catalytic converter
      production, a conservative no-effect level (NOEL) of 1.5 ng/m3 can be derived for
      the sensitizing effect of halogenated Pt salts. In a (reasonable) worst case
      approach, it is assumed that such compounds comprise 1% (0.1%) of the total Pt
      emissions. Applying a safety factor of 10 to account for interindividual
      variability, a guidance value of 15 (150) ng/m3 is derived for catalyst-borne Pt.
      The exposure to Pt in ambient air as measured or predicted is at least two orders
      of magnitude below this guidance range. Rhodium is also contained in automotive
      catalysts, palladium has increasingly substituted Pt, and iridium-based catalysts
      have recently been introduced. Although the database on these platinum group
      metals is rather small, there is no evidence that they pose a health risk to the
      general population.

PMID- 11327391
TI  - Respiratory allergies on the staff of the police force.
AB  - The aim of the study was to evaluate respiratory allergies of an occupational
      nature in the staff of the police force. Five hundred and eighty-five subjects
      were submitted for lung function tests by dynamic spirometry. Subjects with a
      history of respiratory symptoms and border line respiratory function underwent
      bronchial provocation tests with methacholine. If FEV1 was < 80%, a bronchial
      reversibility test was performed. Allergic tests (skin and RAST) for inhalating
      allergens (perennial, seasonal and occupational) were performed. The results
      suggested asthmatic symptoms in 57 subjects, eight of whom were positive to skin
      and RAST tests for occupational inhalating allergens. Among these eight subjects,
      three had FEV1 < 80% of the theoretical value without therapy, and five showed
      obstruction of small caliber airways (MEF 25, MEF 50, FEF 25-75 < 65% of the
      theoretical value). The analysis showed a low percentage of respiratory
      occupational allergies. Among 21 subjects positive to Dermatophagoides, seven
      worked as archivists. In these workers, a concomitant occupational cause for the
      symptomatological and functional pattern was established.

PMID- 11327392
TI  - The role of metals in autoimmune vasculitis: epidemiological and pathogenic
      study.
AB  - BACKGROUND: A possible relationship between Silica (Si) exposure and
      antineutrophil cytoplasm antibodies (ANCA)-associated vasculitis has been
      reported. Furthermore, tuberculosis (TBC) has been frequently described in
      patients with silicosis, and TBC infection shares with ANCA-associated vasculitis
      the formation of granulomas. Therefore, an intriguing network including Silica,
      Vasculitis, TBC and ANCA might be hypothesized. The aim of this work was to
      further investigate these correlations using both epidemiological and pathogenic
      approaches. METHODS: Study I--epidemiological study. A case-control study to
      compare the occupational histories of 31 cases of biopsy proven vasculitis (18
      pauci-immune crescentic glomerulonephritis, 9 microscopic polyangitis, 4
      Wegener's granulomatosis) with those of 58 age, sex and residence-matched
      controls (affected by other kidney diseases), was performed. Occupational Health
      physicians designed an appropriate questionnaire in order to evaluate a wide
      spread of exposures and calculate their entity by the product of Intensity x
      Frequency x Duration. Study II--tuberculosis association. A case-control study to
      evaluate the frequency of a previous history of tuberculosis (TBC) in 45 patients
      with vasculitis and 45 controls were performed. Study III--ANCA positivity. A
      case-control study to evaluate the presence of ANCA was performed by testing
      blood samples of 64 people with previous professional exposure and 65 sex/age
      matched patients hospitalized in a General Medicine Unit. Furthermore, the same
      evaluation was made in a pilot study in 16 patients with ongoing or previous TBC.
      Study IV--experimental study. The oxygen free radicals (OFR) and IL-12 production
      (both involved in the pathogenesis of vasculitis) from human phagocytic cells
      stimulated with an amorphous (diatomaceous earth) and a crystalline (quartz) form
      of Si at the doses of 10 and 100 microg ml(-1) was evaluated. RESULTS: Study I--a
      positive history of exposure to Si resulted in significantly more present in
      cases (14/31 = 45%) than in controls (14/58 = 24%, P = 0.04, OR = 2.4) and no
      other significant exposure association was found (including asbestos, mineral
      oil, formaldehyde, diesel and welding fumes, grain and wood dust, leather,
      solvents, fungicides, bitumen, lead and paint). Study II--past TBC infection was
      significantly more present in patients with vasculitis (12/45 = 26%) than in
      controls (4/45 = 8%, P < 0.05). Study III--ANCA was present in 2/64 exposed
      people (vs. 0/65 controls, P = NS) and 0/16 patients with TBC. Study IV--both
      amorphous and crystalline Si forms represented a stimulus for OFR and IL-12
      production, but quartz resulted as a greater inductor. CONCLUSIONS: We conclude
      that Si exposure might be a risk factor for ANCA-associated vasculitis, possibly
      enhancing endothelial damage by phagocyte generation of oxygen free radicals and
      Th1 differentiation by an excessive IL-12 phagocyte production. Frequency of TBC
      was significantly higher in vasculitis patients. ANCA was not frequent in the
      preliminary examination of people with previous professional exposure or patients
      with TBC, but the number of samples evaluated is too small to allow conclusions.

PMID- 11327393
TI  - Promotion of research on in vitro immunotoxicology.
AB  - ECVAM was established to play a leading role at the European level in the
      independent evaluation of the reliability and relevance of test methods and
      testing strategies for specific purposes through research on advanced methods and
      new test development and validation, so that chemicals and products of various
      kinds, including medicines, vaccines, medical devices, cosmetics, household
      products and agricultural products, can be manufactured, transported and used
      more economically and more safely, whilst the current relevance on animal test
      procedures is progressively reduced. Nowhere is this activity more necessary than
      in the field of immunotoxicology, where we know that chemicals and products of
      many kinds have the potential to stimulate, modulate or suppress the induction or
      expression of various types of immune responses. The problem is to effectively
      evaluate the potency of these effectors, and, since the available information is
      currently based on rather qualitative animal tests, to evaluate the true
      relevance of this knowledge and apply it intelligently in risk assessment
      processes which will protect human beings without unnecessarily limiting the
      development and use of materials which otherwise have economic, health and social
      benefits. The way forward must depend on the following: (a) a better
      understanding of immunotoxicological processes, based on a sounder understanding
      of the immune system itself (and of its network of control systems and
      interrelationships with other body systems); (b) The use of in vitro (not in
      vivo) systems based on human (not animal) cells and tissues; (c) integrated and
      tiered testing strategies, incorporating QSAR, as well as in vitro approaches;
      (d) taking advantage of the use of cells or factors from humans who have been
      exposed to potential immunotoxins, be this voluntarily, occupationally,
      environmentally or by accident; and (e) the recognition that virtually everything
      will effect one or more aspects of the immune system at some dose level and, in
      some circumstances, deciding when such effects are relevant, is the key to
      immunotoxicity testing. Some current ECVAM-sponsored work and activities at ECVAM
      are described.

PMID- 11327394
TI  - Chronic fatigue syndrome following a toxic exposure.
AB  - Chronic fatigue syndrome (CFS) is a clinical entity characterized by severe
      fatigue lasting more than 6 months and other well-defined symptoms. Even though
      in most CFS cases the etiology is still unknown, sometimes the mode of
      presentation of the illness implicates the exposure to chemical and/or food
      toxins as precipitating factors: ciguatera poisoning, sick building syndrome,
      Gulf War syndrome, exposure to organochlorine pesticides, etc. In the National
      Reference Center for CFS Study at the Department of Infectious Diseases of 'G.
      D'Annunzio' University (Chieti) we examined five patients (three females and two
      males, mean age: 37.5 years) who developed the clinical features of CFS several
      months after the exposure to environmental toxic factors: ciguatera poisoning in
      two cases, and exposure to solvents in the other three cases. These patients were
      compared and contrasted with two sex- and age-matched subgroups of CFS patients
      without any history of exposure to toxins: the first subgroup consisted of
      patients with CFS onset following an EBV infection (post-infectious CFS), and the
      second of patients with a concurrent diagnosis of major depression. All subjects
      were investigated by clinical examination, neurophysiological and immunologic
      studies, and neuroendocrine tests. Patients exposed to toxic factors had
      disturbances of hypothalamic function similar to those in controls and, above
      all, showed more severe dysfunction of the immune system with an abnormal CD4/CD8
      ratio, and in three of such cases with decreased levels of NK cells (CD56+).
      These findings may help in understanding the pathogenetic mechanisms involved in
      CFS.

PMID- 11327395
TI  - Lifestyles and mental health status are associated with natural killer cell and
      lymphokine-activated killer cell activities.
AB  - We investigated the association of lifestyle and mental health status with
      natural killer (NK) cell and lymphokine-activated killer (LAK) cell activities in
      healthy males. NK cell activity was determined in 105 male workers and LAK cell
      activity was determined in 54 male workers. Peripheral blood was obtained from
      each subject and peripheral blood mononuclear cells (PBMC) were isolated from the
      blood. These PBMC were used as effector cells. LAK cells were generated by
      incubation of PBMC with interleukin-2 for 72 h. NK cell activity against NK
      sensitive K562 cells and LAK cell activity against NK-resistant Raji cells were
      examined by 51Cr release assay. Overall lifestyles were evaluated according to
      the answers on a questionnaire regarding eight health practices (cigarette
      smoking, alcohol consumption, eating breakfast, hours of sleep, hours of work,
      physical exercise, nutritional balance, mental stress). Subjects with a good
      overall lifestyle showed significantly higher NK cell (P < 0.05) and LAK cell (P
      < 0.05) activities than those with a poor overall lifestyles. Among eight
      lifestyle factors, cigarette smoking has relatively strong effects on NK cell and
      LAK cell activities. Subjects who complained of unstable mental status had
      significantly lower NK cell activity than those who reported stable mental
      status. When subjects were divided into four groups by lifestyle and mental
      health status, subjects who had poor or moderate lifestyle and reported unstable
      mental status showed the lowest NK cell activity and subjects who had good
      lifestyle and reported stable mental status showed the highest NK cell activity
      among four groups.

PMID- 11327396
TI  - Allergens in indoor air: environmental assessment and health effects.
AB  - It has been suggested that the increase in morbidity and mortality for asthma and
      allergies, may also be due to an increase in exposure to allergens in the modern
      indoor environment. Indoor allergen exposure is recognised as the most important
      risk factor for asthma in children. House dust mites, pets, insects, plants,
      moulds and chemical agents in the indoor environment are important causes of
      allergic diseases. House dust mites and their debris and excrements that contain
      the allergens are normally found in the home in beds, mattresses, pillows,
      carpets and furniture stuffing, but they have also been found in office
      environments. Domestic animals such as cats, dogs, birds and rodents may cause
      allergic asthma and rhinoconjunctivitis. The exposure usually occurs in homes,
      but also in schools and kindergartens where domestic animals are kept as pets or
      for education; moreover, cat and dog owners can bring allergens to public areas
      in their clothes. Allergy to natural rubber latex has become an important
      occupational health concern in recent years, particularly among healthcare
      workers; when powdered gloves are worn or changed, latex particles get into the
      air and workers are exposed to latex aerosolised antigens. To assess the
      environmental risk to allergen exposure or to verify if there is a causal
      relationship between the immunologic findings in a patient and his/her
      environmental exposure, sampling from the suspected environment may be necessary.

PMID- 11327397
TI  - Effect of natural allergen exposure on non-specific bronchial reactivity in
      asthmatic farmers.
AB  - The aim of the study was to assess the seasonal variability of non-specific
      bronchial reactivity (NSBR) evaluated with methacholine in asthmatic farmers
      allergic to pollens. Twenty farmers (16 male and four female) with allergy to
      pollens, e.g. 'Graminae' and 'Parietaria', entered the study. None of the
      patients had been previously treated with specific immunotherapy. Patients
      underwent a methacholine challenge at the first visit and then in the subsequent
      seasons. Four groups of tests were obtained according to the period when the
      challenge was performed. Group 1: challenges performed in December, January and
      February; group 2 in March, April and May; group 3 in June, July and August;
      group 4 in September, October and November. PD20 values were expressed as the
      natural logarithm of the cumulative dose of methacholine causing at least a 20%
      fall in FEV1. Bronchial hyperreactivity was highest in summer, followed by spring
      and autumn; in winter it was much lower. Multiple group analysis (ANOVA) showed
      statistically significant differences between the groups (P < 0.01). When the
      groups were compared individually, statistically significant differences existed
      only between group 1 (winter) and each of the other groups, respectively 2
      (spring) (P = 0.02), 3 (summer) (P = 0.004) and 4 (autumn) (P = 0.02). The
      results underlined the importance of allergic inflammation in determining changes
      in NSBR. In the region where the study was carried out (central Italy), the grass
      and Paretaria pollination lasts from March to November. Therefore, farmers had a
      progressive increase in NSBR from spring to summer and a decrease in fall as a
      consequence of the varying pollen concentration in different seasons. The level
      of allergen exposure is, in fact, the main factor that determines the severity of
      bronchial inflammation, thus affecting NSBR.

PMID- 11327398
TI  - Permanent respiratory impairment and upper airway symptoms despite clinical
      improvement in patients with reactive airways dysfunction syndrome.
AB  - We previously reported clinical findings for 19 patients who developed
      symptomatic airways hyperactivity following an acute exposure to an inhaled
      irritant and who were given the diagnosis of reactive airways dysfunction
      syndrome (RADS). We now report on nine of these patients who have been followed
      for a mean of 9 years, allowing assessment of function, symptoms, and comorbidity
      beyond the early phase of acute airway injury and inflammation. None of the
      patients have resolved their airway hyper-responsiveness and symptoms completely,
      although only in one subject, who had a premorbid history of asthma, has the
      condition progressed. A common feature has been sinusitis and other upper-airway
      symptoms. We conclude that in this group of patients, RADS presented in a
      consistent pattern regardless of the cause of airway injury, resolved only
      partially, even in subjects without a premorbid history of respiratory disease,
      and was associated with significant secondary morbidity, especially affecting the
      upper airway. This pattern was evident regardless of smoking status or age at
      time of exposure. We conclude that for these subjects, RADS was a distinct entity
      with a consistent natural history that conferred permanent impairment, but did
      generally improve somewhat over time.

PMID- 11327399
TI  - Allergic inflammation and airway smooth muscle function.
AB  - It is widely accepted that airway smooth muscle (ASM) contraction plays a key
      role in asthmatic attacks. Whether abnormalities of contractility or autonomic
      regulation exist in the asthmatic ASM is still debated. Studies based on
      isometric contraction failed to show differences in the force-generation
      capability between asthmatic and normal ASM. Recent studies in vitro have shown
      that sensitized ASM: (1) shortens more and more rapidly than normal ASM; and (2)
      develops a myogenic response to stretching. The increased velocity of shortening
      may compromise in vivo the ability of tidal cycling to reduce airway tone, which
      would result in an enhanced response to bronchoconstrictor stimuli. The myogenic
      response may result in a sustained bronchospasm after a deep inhalation, a
      maneuver that in normal individuals causes bronchodilatation. Although there is
      no evidence that neural or humoral abnormalities in the autonomic regulation of
      ASM tone are central to the pathogenesis of bronchial asthma, recent data suggest
      that ASM receptor dysfunction may develop secondary to airway allergic response.
      It has been shown that exposure of passively sensitized human bronchi to
      allergens in vitro causes M2- and beta2-receptor dysfunction. Impairment of pre
      junctional M2-autoreceptors may result in an enhancement of neurally mediated
      bronchoconstrictor responses, whereas beta2-receptor dysfunction may reduce the
      sensitivity to bronchodilator treatment. Airway inflammation, which is a
      characteristic feature of bronchial asthma, may alter both the contractile
      properties and the autonomic regulation of ASM. These changes may contribute to
      the severity of asthma, as they may cause an, imbalance between factors favoring
      and opposing airway narrowing.

PMID- 11327400
TI  - Sensitization to environmental antigens in asthmatic children from a central
      Italian area.
AB  - This study was designed to evaluate the frequency of respiratory allergens in
      different age groups of asthmatic atopic children in the Chieti-Pescara area. We
      examined a pediatric population (507 children) aged between 1 to 17 years (mean
      6.62 +/- 2.9). All the children were submitted to a panel of skin prick tests
      (SPT) for 12 common aeroallergens: Grass Pollens (G.), Parietaria (P.), Olive
      (O.), Artemisia (A.), Ragweed (R.), Dermatophagoides Pteronyssinus and
      Dermatophagoides Farinae (D.P. & D.F.), Cat and Dog dander (C.D.), Feathers (F.),
      Alternaria (Al.), Aspergillus (As.). All the subjects gave positive result to one
      or more allergens. The population was subdivided in to 4 groups according to
      their age (Group A: 1-3 years; Group B: 4-6 years; Group C: 7-9 years; Group D:
      10-17 years). In each age group, we determined the number of subjects with 1, 2,
      3, 4 or 5 and more than 5 positive SPT and the prevalence of positive SPT for
      different allergens. We found that 74% of 507 patients showed positive reaction
      to Dermatophagoides Pt, 71% to Dermatophagoides Fa, 45% to Grass, 23% to
      Parietaria, 21% to Olive, 17% to Artemisia, 17% to Cat's or Dog's danders, 13% to
      Alternaria, 5.9% to Ragweed, 5.9% to Feathers, and 4% to Aspergillus. In addition
      we detected that 12% of children examined were monosensitized; 56% were
      sensitized to 2 or 3 allergens; 22% were sensitized to 4 or 5 allergens, and then
      8% were polysensitized to > 5 allergens. The allergy to grass pollens and to
      house dust mites was the most frequent in monosensitized. In the older patients,
      we found an increase in number of positives SPT to several allergens, and an
      increase in the frequency of Gr., P. and O. allergy, while the house dust mites
      sensitization remained constant in all groups and represented the dominant cause
      of asthmatic symptoms in this population. Our data confirm the importance of age
      in determining a respiratory polysensitization. In conclusion, our data suggest
      that house dust mites (D.P. and D.F.) and grass pollens are the most common
      allergens in asthmatic children of the Chieti-Pescara area.

PMID- 11327401
TI  - Bronchial hyperactivity in bakers and its relation to atopy and skin reactivity.
AB  - Data from literature suggests that a significant percentage of bakers develop
      occupational asthma and chronic obstructive bronchitis, the primary reason for
      this being the strong allergenic properties of flour. The aim of this study was
      to evaluate the prevalence of bronchial hyperactivity in bakers, as well as to
      correlate bronchial hyperactivity with positive skin tests and atopy. A group of
      100 bakers (54 males and 46 females) employed in bread production for an average
      of 14.8 +/- 8.8 years, were examined from 1996 to 1999. Bronchial challenge tests
      with methacholine (cumulative dose of 4 mg) and flour were performed. It was
      considered positive if a FEV1 reduction of at least 20% from normal values had
      occurred. Additionally, skin prick tests were performed with wheat flour
      extracts, as well as standard environmental inhalation allergens. Total IgE were
      assessed using the ELISA method. Results showed that 11% of bakers demonstrated a
      positive methacholine test, 2% of bakers responded to the specific bronchial
      challenge test with wheat flour. The skin prick test with wheat flour was
      positive in 15% of bakers, while the same test using standard inhalation
      allergens was positive in 12% of bakers. Atopic status was found in 18% of
      bakers. The frequency of positive methacholine test was 33% in bakers with atopic
      status, compared to 6.1% (P < 0.01) in those without atopic status. Among the
      bakers who displayed a positive skin test to wheat flour, specific bronchial
      challenge test with flour was positive in two (13.3%) bakers, while no response
      to the bronchial challenge test with flour was observed in bakers with negative
      skin test. This is in agreement with known results.

PMID- 11327402
TI  - Mast cell activation in acquired chronic urticaria-angioedema.
AB  - Mast cells play a central role in the pathogenesis of many allergic disorders.
      They can be activated in different ways. The present study was focused to
      evaluate the role of mast cells in acquired chronic urticaria-angioedema induced
      by gastroesophageal reflux. Tryptase, an important marker of mast cell
      activation, was detected with UniCap Tryptase Fluoroenzymeimmunoassay (Pharmacia
      & Upjohn AB, Uppsala, Sweden). Eight subjects were studied: four males and four
      females, aged between 29 and 71 years (mean age: 45 yrs.), suffering from
      acquired chronic urticaria-angioedema. Results were compared with the results of
      seven healthy control subjects. Moreover, data were compared with those of 13
      subjects (10 males and 3 females, mean age: 24.7 years) suffering from allergic
      rhinitis. In acquired chronic urticaria-angioedema, serum tryptase levels (mean
      +/- S.D.: 9.6 +/- 4.3 microg/l) were significantly higher (P < 0.007) than those
      of the controls (mean +/- S.D.: 3.0 +/- 1.2 microg/l) and higher also than in
      allergic rhinitis (mean +/- S.D.: 6.1 +/- 2.4 microg/l, P < 0.03). The results
      underline the central role of mast cells in the inflammation of acquired chronic
      urticaria-angioedema.

PMID- 11327403
TI  - Prevalence of sensitization to Cupressus sempervirens: a 4-year retrospective
      study.
AB  - In the last few years Cupressus sempervirens has been identified as the cause of
      an increasing number of cases of late winter-early spring pollinosis in
      Mediterranean countries. We conducted a 4-year retrospective study of a large
      group of subjects with documented allergic respiratory disease in order to
      determine the prevalence, clinical significance and annual rate of sensitization
      to C. sempervirens pollen. Anamnestic data and skin prick tests (SPT) with common
      aeroallergens and C. sempervirens extract were collected from 1397 subjects (712
      male and 685 female) resident in Latium, a region in central Italy, with
      complaints related to upper- or lower-respiratory-tract disorders or conjunctival
      disease. Two hundred and forty-three subjects (17.4%) showed positive results to
      C. sempervirens extract: 47 (19.3%) of them were monosensitized. The annual
      sensitization rate of SPT positivity to C. sempervirens varied from 7.2% in 1995
      to 22% in 1998. All the subjects monosensitized to cypress pollen had symptoms
      from January through April. Our study suggests that sensitivity to C.
      sempervirens is responsible for respiratory symptoms in an increasing percentage
      of subjects. Further studies are needed to determine its frequency at the
      national level.

PMID- 11327404
TI  - Occupational dermatitis in a highly industrialized Italian region: the experience
      of four occupational health departments.
AB  - There is a need for several research centers to carry out coordinated large-scale
      evaluation of the spread of occupational irritant and allergic dermatitis. The
      Occupational Health Departments of Bergamo, Brescia, Lecco and Cremona therefore
      decided to join their experiences and bring together all the cases of
      occupational irritant and allergic dermatitis diagnosed by these Departments
      between 1993 and 1998. In this period, 1169 cases of occupational dermatitis were
      diagnosed, subdivided into 768 cases of allergic contact dermatitis (ACD), 337 of
      irritant contact dermatitis (ICD), 54 of urticaria and 10 of airborne contact
      dermatitis, and there has not been a trend towards increase of occupational
      dermatitis over the years. Our population included 724 males and 445 females and
      average latency after the beginning of exposure to occupational allergens was
      8.01 years for ACD, 6.4 for ICD, 3.22 for urticaria and 5.57 for airborne contact
      dermatitis. The frequency of atopy was 33.9%, in females and 19.5% in males. The
      frequency of atopy was particularly high (89%) in subjects with urticaria. Among
      subjects with allergic dermatitis, 362 had had only one sensitization while 406
      had had two or more sensitizations. The working areas where we found the highest
      number of ACD were metal working industry, building, health care workers and
      hairdressers and the frequency of ICD was high in metal workers and health care
      workers. Most of the cases of urticaria were diagnosed in health care workers
      (68.5%) and the main causing agent was latex. These are only preliminary data but
      occupations at risk and the substances expected to be the most frequent
      etiological agents do not differ significantly from those reported in the
      literature. It is hoped that as a result of this project there will be in the
      future: standardization of diagnostic procedures, uniform assessment of
      allergological risk in working environments not yet fully investigated,
      standardization of preventative measures and proper evaluation of their
      effectiveness.

PMID- 11327405
TI  - Occupational allergic contact dermatitis in Singapore.
AB  - Singapore has a resident population of 3,000,000 and a workforce of 1,780,000.
      Most are employed in manufacturing, services and commerce (245,000). From 1996 to
      1998, 3472 cases were notified to the Ministry of Manpower and confirmed as
      occupational diseases. Noise-induced hearing loss accounted for 82% of cases,
      while only 11% of cases were industrial dermatitis. Occupational allergic contact
      dermatitis was not common, comprising approximately one third of the 369 cases of
      industrial dermatitis that were notified. However, we believe that the majority
      of cases are not notified to the authorities. The main occupational contact
      allergens were chromates, nickel, rubber chemicals, cutting fluids and resins.
      Most affected workers were from the construction, electronics and metalworking
      industries. Case series of occupational dermatoses among electronics and metal
      workers have been published. Of the cases of occupational dermatoses among
      electronics workers seen at a tertiary dermatological centre, 41% of 149 had
      allergic contact dermatitis (ACD). The commonest allergens were nickel, resins
      and rubber chemicals. In another case series of 252 metalworkers seen at the same
      dermatological centre, 23% suffered from ACD. The common allergens were metals
      and cutting fluids. Besides the common causes of ACD, unusual allergens have also
      been described. One example is ACD to grasses, which is seen mainly among
      military personnel. Population studies have been conducted in several industries.
      A survey of 2567 electronics workers revealed a 2% point prevalence of ACD. Of
      the occupationally relevant cases, 46 were nickel sensitive, 7 reacted to
      colophony, and 1 case to epoxy resin. A study of 272 prefabrication construction
      workers showed a 14% prevalence rate of occupational dermatitis. Of the 38 cases,
      42% were ACD to chromates and rubber chemicals. Occupational ACD in Singapore is
      not as uncommon as the reported statistics suggest. Population-based reports,
      which overcome the problem of under-notification, show that the prevalence is
      variable in different industries.

PMID- 11327406
TI  - Alarming wear of the first-generation polyethylene liner of the cementless porous
      coated Biomet Universal cup: 107 hips followed for mean 6 years.
AB  - Wear of the socket liner and resulting osteolysis are the major causes of failure
      in cementless hip arthroplasties. We report alarming wear of the first-generation
      polyethylene liner of the cementless porous-coated Biomet Universal cup.
      Radiographs of 107 primary hip arthroplasties were analyzed retrospectively. The
      mean follow-up time was 74 (47-91) months. The linear wear of the polyethylene
      liners was assessed using a modification of the Livermore method. The median
      linear wear was 1.0 (0-6.2) and the median linear wear rate was 0.17 mm/year.
      There was a statistically significant difference between the 28 mm and 32 mm
      femoral head groups both in the volumetric wear and in the volumetric wear rate.
      The median linear wear was 0.28 mm/year and 0.14 mm/year for the 32 mm and 28 mm
      heads, respectively. So far, 14 revisions have been performed or have been
      scheduled because of excessive wear of the polyethylene liner. In regression
      analysis, the factors related to the wear rate were the 32 mm size of the femoral
      head and screw fixation of acetabular shell. We found that the cases with calcar
      rounding were associated with significantly greater wear. Possible reasons for
      increased wear of the Hexloc liner may be the cylindrical design, thin
      polyethylene, and poor quality of the polyethylene. Regular clinical and
      radiographic follow-ups are recommended especially for hips with 32 mm femoral
      heads or with screw fixation. If progressive wear of the liner is observed,
      revision must be considered.

PMID- 11327407
TI  - Gluteus minimus-induced femoral head deformation in dysplasia of the hip.
AB  - Lateral notching of the femoral head is considered pathognomonic for spastic
      subluxation of the hip. Less frequently, flattening is seen with extrusion of the
      femoral head in nonspastic hip dysplasia. The aim of this study was to throw
      light on its underlying pathomechanism. On the radiographs of 297 hips with
      developmental dysplasia, lateral flattening of the femoral head was seen in 18
      hips (6%), but notching was present in only 1. Of 7 dysplasias due to cerebral
      palsy, 6 showed lateral notching. The gluteus minimus was felt to be responsible
      for the lateral femoral head changes as the muscle counteracts lateral migration
      of the femoral head. Intraoperative dissection of 3 hips supported this view. 1
      hip with developmental dysplasia and lateral notching was subjected to a
      periacetabular osteotomy. At surgery, the tendon of the gluteus minimus was found
      to fit tightly into the notch. Of 2 hips with spastic dysplasia, 1 presented with
      and the other without lateral notching. In the hip with lateral notching, the
      gluteus minimus had a normal appearance and it lay in the defect of the femoral
      head. In the hip without notching, the gluteus minimus was atrophied with signs
      of fatty degeneration. We therefore believe that lateral notching is a sign of
      hypertonicity of the gluteus minimus muscle.

PMID- 11327408
TI  - Femoral head dysplasia in Morquio disease type A: bilateral varus osteotomy of
      the femur.

PMID- 11327409
TI  - Correlation of wear debris-induced osteolysis and revision with volumetric wear
      rates of polyethylene: a survey of 8 reports in the literature.
AB  - This survey focused on clinical reports of polyethylene wear and osteolysis in
      total hip replacements. With regard to documentation of clinical wear-rates, 57
      publications were reduced to an analysis of 8 reports of THR series, including
      the incidence of osteolysis. A direct correlation was found among volumetric wear
      rates, incidence of osteolysis and revision rates in THR concepts of the 1983
      1987 era. As volumetric wear rate increased, the incidence of osteolysis and
      revision rates increased. With regard to our grading system for volumetric wear,
      with follow-up in the 4-15 year range, osteolysis was rare in group A (wear = 0
      80 mm3/year), ranging from 6% to 31% in group B (wear 40-80 mm3/year) and from
      21% to 100% in group C (wear > 140 mm3/year). With regard to cup design, the
      optimal low-wear group had mainly cemented polyethylene cups with 22 and 28 mm
      head sizes. The mid-wear group B had metal-backed cemented and uncemented cups,
      with 28 mm head size, and the high-risk group C had only uncemented, metal-backed
      cups, with the highest wear in the 32 mm head size. Less than 10 years of follow
      up did not distinguish adequately between different designs of THR, except in a
      few cases which had early failures due to material or design deficiencies.
      Overall, the cemented all-polyethylene cup combined with the smaller ball head
      proved to be better.

PMID- 11327410
TI  - Cement penetration in the proximal femur does not depend on broach surface
      finish.
AB  - In a cadaver study, we prepared 29 paired human cadaver femora using 3 different
      broaches of identical geometry but different surface characteristics. In one
      group of 20 pairs, preparation with chipped-toothed broaches was compared to
      diamond-shaped broaches; in the other group of 9 pairs, polished tamps for
      compaction of cancellous bone were compared with chipped-tooth broaches.
      Cancellous bone was irrigated with 1 liter pulsed lavage. The specimens were
      embedded in specially-designed pots. Palacos R and Simplex bone cements were
      used. After vacuum mixing, the cement was applied in a retrograde manner and
      subjected to a standard pressure protocol with a constant force of 3,000 N.
      Radiographs were taken and horizontal sections were obtained at predefined levels
      using a diamond saw. Microradiographs were taken, digitized and analyzed to
      assess cement penetration into cancellous bone. In 6 of 9 femora prepared using
      smooth tamps, femoral fractures occurred despite careful preparation technique.
      The microradiographic evaluation showed no significant morphometric differences
      between diamond and chipped-tooth or between polished and chipped-tooth broaches
      with regard to cement penetration into cancellous bone. Therefore, in the
      presence of pulsed lavage, one finds no significant effect of broach surface
      characteristics on cement penetration into cancellous bone of the proximal end of
      the femur.

PMID- 11327411
TI  - Reliability of the AO/ASIF classification for pertrochanteric femoral fractures.
AB  - 20 radiographs of pertrochanteric femoral fractures were classified as to
      fracture "group" and "sub-group" according to the AO/ASIF Fracture Classification
      (type 31A) by 15 observers. 3 months later, the same radiographs were reviewed by
      the same observers. Mean agreement of the observers with the final consensus
      ranged from 53% (with subgroup classification) to 81% (without subgroup). The
      mean kappa value for interobserver reliability was 0.33 and 0.34 for
      classification with subgroup in both observer sessions, respectively. Omission of
      the subgroup classification resulted in better mean kappa values (0.67 and 0.63,
      respectively). Mean intraobserver reliability was 0.48 in the fracture "subgroup"
      and 0.78 in the "group" classification. In conclusion, the results show that the
      AO/ASIF classification for pertrochanteric fractures is reliable for fracture
      subgroups 31A1, A2 or A3. The group classification should be used to compare
      scientific data and determine the best treatment. Further classification of
      fracture subgroups leads to poor reproducibility of results.

PMID- 11327412
TI  - Postphlebitic syndrome after total knee arthroplasty: 405 patients examined 2-10
      years after surgery.
AB  - We assessed the prevalence and relevance of putative risk factors for significant
      postphlebitic syndrome (PPS) in a cohort of 405 patients who underwent single
      limb cemented total knee arthroplasty. All patients were studied by means of a
      questionnaire and clinical examination to detect the presence of lower limb
      venous insufficiency. We found 52 (13%) new cases of postphlebitic syndrome.
      Comparison of those patients with and without PPS revealed no significant
      differences in the median age, sex ratio, preoperative mass, primary joint
      pathology or relevance of primary or revision surgery. A confirmed history of pre
      or post-operative deep vein thrombosis was associated with the development of
      disease. Most cases seemed to develop within 5 years of surgery.

PMID- 11327413
TI  - Bone debridement and limb lengthening in type III open tibial shaft fractures: no
      infection or nonunion in 9 patients.
AB  - We retrospectively reviewed a consecutive series of 9 patients with tibial shaft
      fractures and extensive soft tissue damage, who had completed treatment by means
      of bone resection and distraction. 4 patients had type IIIB fractures and 5 type
      IIIC. The median follow-up time after bone resection was 27 (12-43) months. All
      patients were treated with debridement of devitalized soft tissue and resection
      of dead bone at the fracture site. The median bone shortening was 4 (3-9) cm.
      Equal limb-length was restored by proximal corticotomy and lengthening. A free
      vascular flap in 5 patients and a local flap in 4 patients corrected the soft
      tissue loss. All soft tissue transfers were successful, except in 1 case, which
      healed after a new free flap was made. The median union time of the fracture was
      8 (4.5-28) months from the injury and 7 (3-10) months from the time of bone
      resection. There were no deep infections or nonunions and no secondary
      amputations. This series shows that bone debridement and limb lengthening, with a
      multidisciplinary approach, is often successful in salvaging limbs at high risk
      of amputation.

PMID- 11327414
TI  - Reduced tibial torsion in congenital clubfoot: CT measurements in 24 patients.
AB  - We determined leg torsion with CT scans through the femoral condyles and the
      ankle joints in 24 children (17 boys) with congenital clubfoot. In 16 cases,
      there was a bilateral clubfoot, in 5 cases it was left-sided and in 3 cases, it
      was on the right side. These children were compared to 17 healthy boys and 7
      girls. The ages of all children ranged between 3 and 12 years. The average
      external torsion of the leg in the patients with clubfoot was 20 (15) versus 31
      (7) degrees in the healthy children (p = 0.002). This study shows that there are
      great variations in leg torsion in children with congenital clubfoot and, on
      average, the external torsion is significantly lower than in healthy subjects.

PMID- 11327415
TI  - Radiostereometric analysis of distal radial fracture displacement during
      treatment: a randomized study comparing Norian SRS and external fixation in 23
      patients.
AB  - In a randomized study, we included 23 osteoporotic patients with a distal radial
      fracture and loss of reduction after 1 week. The facture was re-reduced. In one
      group, a self-setting hydroxyapatite, Norian SRS, was injected into the fracture
      and the wrist was immobilized for 2 weeks with a dorsal splint (n 12). In the
      other group, the fracture was immobilized for 5 weeks with an external fixator (n
      11). During the operation, the fracture fragments were marked with tantalum
      markers, so that loss of reduction during the immobilization and after
      mobilization could be studied with radiostereometric analysis (RSA). We found
      some recurrence of compression in the fracture in both groups during
      immobilization. After mobilization, the motion of the fracture, measured by
      displacement of the fragments along the longitudinal axis, was less than 2 mm,
      except in 3 cases treated with Norian SRS. A compression along the longitudinal
      axis of less than 2 mm is not likely to cause any problem in the long term. From
      the first to the last investigation, 7/12 patients with Norian SRS and 4/11 with
      external fixation lost more than 2 mm of the reduction along the longitudinal
      axis. We conclude that 5 weeks of immobilization is sufficient for healing with
      external fixation in this age group. This immobilization time might be reduced to
      2 weeks for fractures treated with Norian SRS, but additional hardware should be
      used to ensure stability of the fracture system.

PMID- 11327416
TI  - Bone density and geometric properties of the distal radius in displaced and
      undisplaced Colles' fractures: quantitative CT in 70 women.
AB  - We examined cortical and trabecular bone density and geometric properties of the
      unfractured distal radius in 70 women with recent Colles' fractures, using
      multilayer peripheral quantitative computed tomography (pQCT). We found that
      cortical volumetric density, cortical area and mean cortical thickness were lower
      in the displaced than in the undisplaced fractures, suggesting that the cross
      sectional volumetric density and geometric properties of cortical bone may be
      essential in determining the severity of a Colles' fracture. We also compared
      lumbar spine and femoral neck bone mineral density (BMD) and the occurrence of
      osteoporosis in the displaced and undisplaced fracture groups and found no
      significant difference, which suggests that displacement of a Colles' fracture is
      not associated with general osteoporosis.

PMID- 11327417
TI  - The lumbar interpediculate distance is widened in adults with the Marfan
      syndrome: data from 32 cases.
AB  - 32 patients with Marfan syndrome, diagnosed with DePaepe's criteria, volunteered
      for this study. All patients underwent standard anteroposterior radiographs of
      the lumbar spine. Interpediculate distances (IPD) at each level were compared to
      those of previously established norms. Criteria were developed to determine the
      presence of Marfan using "cut-off values" for the IPDs at each lumbar level. The
      IPDs were significantly larger in the Marfan patients at all lumbar levels. Cut
      off values were calculated setting the specificity at 95% at each lumbar level.
      The cut-off value at L4 yielded the greatest sensitivity. We conclude that the
      IPDs are widened in patients with Marfan syndrome. The IPD at L4 is a good
      criterion for Marfan with specificity of 95% and sensitivity of 75%. One must
      consider using this as a skeletal criterion or a screening tool for Marfan.

PMID- 11327418
TI  - Soft-tissue sarcoma of the thigh: surgical margin influences local recurrence but
      not survival in 152 patients.
AB  - Between 1979 and 1998, 152 patients with a soft-tissue sarcoma arising in the
      thigh were surgically treated in the Sarcoma Center in Aarhus, Denmark. We
      studied clinicopathologic factors prognostic for local recurrence and survival.
      27 patients (18%) had a low-grade tumor, 26 (17%) an intermediate-grade and 99
      (65%) a high-grade tumor. 27 patients (18%) were amputated and 125 (82%) had a
      local resection. 21 (14%) underwent a marginal resection, 82 (54%) a wide
      resection and 49 (32%) a compartmental resection. 32 patients were also given
      radiotherapy, 11 of these had a marginal resection. The 5-year local recurrence
      free rate was 91%. Multivariate analysis selected marginal resection and
      histological high grade as unfavorable prognostic factors for local recurrence.
      The 5-year survival rate was 68%. High age and histological high grade were
      unfavorable prognostic factors for survival in a multivariate analysis. Surgical
      margin influenced local recurrence, but not the overall survival.

PMID- 11327419
TI  - Fibrous tissue armoring increases the mechanical strength of an impacted bone
      graft.
AB  - Impacted, morselized bone allografts are used with good clinical results in
      revision of hip prostheses with loosening and osteolysis. The impacted bone graft
      appears radiographically to remodel, but histological analyses have shown a
      heterogeneous picture with a mixture of living and dead bone. Thus, complete
      remodeling of the graft may be neither a prerequisite nor a cause of the good
      clinical results. The present study concerns the mechanical effect of the mere
      armoring of the bone graft by ingrowing fibrous tissue. We compared the
      compression strength of freshly-impacted grafts to grafts that had been inserted
      into a bone chamber and thus were penetrated by fibrous tissue growing in between
      the graft trabeculae. The compressive strength was doubled after 4 weeks of
      fibrous ingrowth. We conclude that the mechanical properties of an impacted graft
      are enhanced by armoring with ingrowing fibrous tissue. Strengthening of the
      parts of the impacted grafts which have not yet remodeled, would be clinically
      relevant for the outcome of the operation, since these parts are at high stress
      during the whole remodeling period. Complete osseous remodeling may not be
      necessary to obtain a good clinical result with a morselized impacted graft.

PMID- 11327421
TI  - High-pressure saline washing of allografts reduces bacterial contamination.
AB  - 60 fresh-frozen bone allografts were contaminated on the operating room floor. No
      bacterial growth was detected in 5 of them after contamination. The remaining 55
      grafts had positive bacterial cultures and were processed with three methods:
      soaking in saline, soaking in antibiotic solution or washing by high-pressure
      saline. After high-pressure lavage, the cultures were negative in three fourths
      of the contaminated allografts. The corresponding figures after soaking grafts in
      saline and antibiotic solution were one tenth and two tenths, respectively. High
      pressure saline cleansing of allografts can be recommended because it improves
      safety by reducing the superficial bacterial bioburden.

PMID- 11327420
TI  - Rotational acetabular osteotomy for hip dysplasia: spontaneous medial enlargement
      of the acetabulum.
AB  - We followed 56 patients (63 joints) who had undergone rotational acetabular
      osteotomy (RAOs) between 1987 and 1993, mean 7 (5-12) years. The Merle d'Aubigne
      score increased by 15 points or more in 59 and decreased in 4 hips. The arthrosis
      progressed in 5 joints. In about 2/3 of the cases, we observed some medial and/or
      lateral expansion of the subchondral bone in the acetabulum 3 years
      postoperatively, suggesting enlargement of the load-bearing area.

PMID- 11327422
TI  - No effect of methacrylate-based bone cement CMW 1 on the plasmatic phase of
      coagulation, red blood cells and endothelial cells in vitro.
AB  - The compatibility of a methacrylate-based bone cement (CMW 1, DePuy International
      Ltd, England) used for the fixation of joint prostheses was evaluated on plasma,
      an erythrocyte suspension and cultured human endothelial cells. The extract of
      the cement was tested, following 1 hour and 7 days of curing. After the contact
      in vitro of the extract with plasma, activated partial thromboplastin time,
      antithrombin III, thrombin-antithrombin complexes and fibrin degradation products
      were assayed. Hemolytic activity was tested by adding the cement extracts to a
      suspension of erythrocytes. After 4 hours of incubation at 37 degrees C, the
      hemoglobin concentration was determined on the supernatants by the colorimetric
      method. The effect of the cement on tissue factor and thrombomodulin production
      was evaluated on human umbilical vein endothelial cell cultures. Tissue factor
      was determined in cell lysates by enzyme immunoassay, following 4 hours'
      incubation of cultures with the cement extract. Thrombomodulin was assayed in
      cell lysates by enzyme immuno assay, after 24 hours' incubation with the cement
      extract. The response to all trans-retinoic acid (ATRA) was tested. The cement
      caused no significant modifications of the coagulation tests, had no hemolytic
      activity, did not determine tissue factor production and did not modify
      thrombomodulin, compared to the negative control. The response to stimulation
      with ATRA was similar to that of the negative control. We conclude that the
      cement extract does not affect the plasmatic phase of coagulation, has no effect
      on erythrocytes, does not induce the expression of procoagulant activity by
      endothelial cells and does not impair their antithrombotic property, within the
      limits of the tests performed.

PMID- 11327423
TI  - Spontaneous bilateral displaced femoral neck fractures in nutritional
      osteomalacia--a case report.

PMID- 11327424
TI  - HRSA awards more than $500 million for HIV/AIDS care.

PMID- 11327425
TI  - Heart failure, diastolic dysfunction and the role of the family physician.

PMID- 11327426
TI  - Group A beta-hemolytic streptococcal pharyngitis.

PMID- 11327427
TI  - Comments on management of the drug-seeking patient.

PMID- 11327428
TI  - Comments on management of the drug-seeking patient.

PMID- 11327429
TI  - Evaluation and differential diagnosis of dyspareunia.
AB  - Dyspareunia is genital pain associated with sexual intercourse. Although this
      condition has historically been defined by psychologic theories, the current
      treatment approach favors an integrated pain model. Identification of the
      initiating and promulgating factors is essential to reaching a successful
      diagnosis. The differential diagnoses include vaginismus, inadequate lubrication,
      atrophy and vulvodynia (vulvar vestibulitis). Less common etiologies are
      endometriosis, pelvic congestion, adhesions or infections, and adnexal pathology.
      Urethral disorders, cystitis and interstitial cystitis may also cause painful
      intercourse. The location of the pain may be described as entry or deep.
      Vulvodynia, atrophy, inadequate lubrication and vaginismus are associated with
      painful entry. Deep pain occurs with the other conditions previously noted. The
      physical examination may reproduce the pain, such as localized pain with vulvar
      vestibulitis, when the vagina is touched with a cotton swab. The involuntary
      spasm of vaginismus may be noted with insertion of an examining finger or
      speculum. Palpation of the lateral vaginal walls, uterus, adnexa and urethral
      structures helps identify the cause. An understanding of the present organic
      etiology must be integrated with an appreciation of the ongoing psychologic
      factors and negative expectations and attitudes that perpetuate the pain cycle.

PMID- 11327430
TI  - Dyspareunia: what it might mean fo you.

PMID- 11327431
TI  - Management of Group A beta-hemolytic streptococcal pharyngitis.
AB  - Bacteria are responsible for approximately 5 to 10 percent of pharyngitis cases,
      with group A beta-hemolytic streptococci being the most common bacterial
      etiology. A positive rapid antigen detection test may be considered definitive
      evidence for treatment; a negative test should be followed by a confirmatory
      throat culture when streptococcal pharyngitis is strongly suspected. Treatment
      goals include prevention of suppurative and nonsuppurative complications,
      abatement of clinical signs and symptoms, reduction of bacterial transmission and
      minimization of antimicrobial adverse effects. Antibiotic selection requires
      consideration of patients' allergies, bacteriologic and clinical efficacy,
      frequency of administration, duration of therapy, potential side effects,
      compliance and cost. Oral penicillin remains the drug of choice in most clinical
      situations, although the more expensive cephalosporins and, perhaps, amoxicillin
      clavulanate potassium provide superior bacteriologic and clinical cure rates.
      Alternative treatments must be used in patients with penicillin allergy,
      compliance issues or penicillin treatment failure. Patients who do not respond to
      initial treatment should be given an antimicrobial that is not inactivated by
      penicillinase-producing organisms (e.g., amoxicillin-clavulanate potassium, a
      cephalosporin or a macrolide). Patient education may help to reduce recurrence.

PMID- 11327432
TI  - Strep throat.

PMID- 11327433
TI  - Prevention and treatment of dog bites.
AB  - Almost one half of all dog bites involve an animal owned by the victim's family
      or neighbors. A large percentage of dog bite victims are children. Although some
      breeds of dogs have been identified as being more aggressive than other breeds,
      any dog may attack when threatened. All dog bites carry a risk of infection, but
      immediate copious irrigation can significantly decrease that risk. Assessment for
      the risk of tetanus and rabies virus infection, and subsequent selection of
      prophylactic antibiotics, are essential in the management of dog bites. The dog
      bite injury should be documented with photographs and diagrams when appropriate.
      Family physicians should educate parents and children on ways to prevent dog
      bites.

PMID- 11327434
TI  - Preventing dog bites.

PMID- 11327435
TI  - Conduct disorder: diagnosis and treatment in primary care.
AB  - Conduct disorder is a common childhood psychiatric problem that has an increased
      incidence in adolescence. The primary diagnostic features of conduct disorder
      include aggression, theft, vandalism, violations of rules and/or lying. For a
      diagnosis, these behaviors must occur for at least a six-month period. Conduct
      disorder has a multifactorial etiology that includes biologic, psychosocial and
      familial factors. The differential diagnosis of conduct disorder includes
      oppositional defiant disorder, attention-deficit/hyperactivity disorder (ADHD),
      mood disorder and intermittent explosive disorder. Family physicians may provide
      brief, behaviorally focused parent counseling, pharmacotherapy and referral for
      more intensive family and individual psychotherapy.

PMID- 11327437
TI  - How to stay out of the hospital if yor have congestive heart failure.

PMID- 11327436
TI  - Reducing readmissions for congestive heart failure.
AB  - Hospital admission for congestive heart failure is extremely common and quite
      expensive, although it is frequently preventable. New drugs and therapies have
      been reported to reduce admissions, decrease morbidity and mortality, and improve
      the quality of life for these patients. Patients with an ejection fraction less
      than 40 percent (decreased systolic function) should be treated with medication
      to improve symptoms and prevent progression of heart failure. Angiotensin
      converting enzyme (ACE) inhibitors are a mainstay of treatment in patients who
      can tolerate them; in patients who cannot take these drugs, angiotensin II
      receptor blocking agents offer an alternative. Patients with New York Heart
      Association class II or III heart failure should also receive a beta blocker
      (metoprolol, carvedilol or bisoprolol). Recent research has shown that treatment
      with spironolactone improves mortality and hospital readmission rates. An
      exercise program should also be recommended for all patients with heart failure
      unless their condition is unstable.

PMID- 11327438
TI  - PHS updates smoking cessation guideline.

PMID- 11327439
TI  - Detection and quantification of human cytomegalovirus (CMV) as a marker for
      development of CMV disease and survival in patients with AIDS.

PMID- 11327440
TI  - The role of stavudine in the management of adults with HIV infection.
AB  - Combinations of two nucleoside analogue reverse transcriptase inhibitors plus a
      third agent represent the current standard for antiretroviral therapy. Stavudine
      is a nucleoside analogue that demonstrates in vitro activity against human
      immunodeficiency virus type 1 (HIV-1) and HIV-2 within an acceptable therapeutic
      index in a range of T lymphocyte and haematopoietic precursor cell lines. It is
      additive or synergistic in vitro with a number of other antiretrovirals including
      protease inhibitors in two and three way combinations and is active against
      zidovudine-resistant virus. It exhibits excellent oral bioavailability, with CSF
      penetration. In clinical use, stavudine exhibits antiretroviral activity as a
      monotherapy similar to zidovudine, and is of proven clinical benefit in
      zidovudine-pretreated patients. In combination with didanosine and/or nelfinavir
      it results in more substantial and durable responses in immunological and
      virological markers than reported with either drug alone. Comparative trials in
      zidovudine-experienced patients suggest a similar frequency of adverse events to
      that observed with zidovudine. Peripheral neuropathy is the most common dose
      limiting toxicity with haematological and hepatic function disturbance being
      infrequent. Reasons for stavudine failure are not established, with no consistent
      genotypic pattern being associated with changes in stavudine sensitivity in vitro
      or in vivo. The role of stavudine is as a component of triple therapy regimens
      both in initial therapy and in patients with prior zidovudine experience.

PMID- 11327441
TI  - A pilot study of a combination of three reverse transcriptase inhibitors in HIV-1
      infection.
AB  - The objective of this study was to evaluate the efficacy and tolerability of a
      combination of three reverse transcriptase inhibitors in patients with human
      immunodeficiency virus type 1 (HIV-1) infection. The investigation was an open
      pilot study of 48 weeks duration. Forty-five patients with CD4 cell counts
      between 50 and 500 cells/mm3 received a combination of oral zidovudine (200 mg
      three times daily) plus didanosine (200 mg twice daily) and lamivudine (150 mg
      twice daily). Plasma HIV-1 RNA and CD4 cell levels were measured weekly during
      the first month, at weeks 6, 8 and monthly thereafter. HIV-1 RNA levels were also
      measured sequentially in the lymph nodes of five patients after the initiation of
      therapy, and after several months of undetectable plasma RNA in 10 additional
      cases. Sequencing was performed on virus from the peripheral blood mononuclear
      cells of a subset of 14 patients after a mean period of 11+/-1 months on therapy.
      The mean (+/-SE) plasma viral load was 5.04+/-0.09 log10 copies/ml and the mean
      CD4 cell count was 339+/-14 cells/mm3 at baseline. Plasma HIV-1 RNA levels
      decreased exponentially in each case and became undetectable in 36 out of 42
      cases who continued therapy for 24 weeks. HIV-1 RNA levels were < 20 copies/ml in
      73% of these cases with undetectable HIV RNA. HIV-1 RNA decreased exponentially
      in lymph nodes after the initiation of therapy. The mean residual lymph node HIV
      1 RNA level was 3.06+/-0.58 log10 copies/10(6) cells in 10 patients evaluated
      after several months of having undetectable plasma HIV RNA levels. A mean gain of
      212 and 237 CD4 cells/mm3 was observed at 24 and 48 weeks, respectively. Proviral
      DNA sequencing showed that the main resistance codon mutations were absent in
      each case. Only one patient presented with a mutation resulting in the K219Q
      substitution, and one other with a T200I substitution. We conclude that this
      combination can achieve a significant decrease in HIV-1 replication in both
      plasma and lymph nodes in most cases. It is safe, able to delay the selection of
      resistant mutants, and keeps open the option for the use of protease inhibitors
      in case of therapeutic failure.

PMID- 11327442
TI  - Zidovudine monotherapy versus zidovudine plus zalcitabine combination therapy in
      HIV-positive persons with CD4 cell counts 300-500 cells/mm3: a double-blind
      controlled trial. The M50003 Study Group Coordinating and Writing Committee.
AB  - OBJECTIVE: To assess the safety and clinical and immunological activity of
      zalcitabine/zidovudine combination therapy compared with zidovudine monotherapy
      in persons with no or limited antiretroviral experience and CD4 counts of 300-500
      cells/mm3. DESIGN AND SETTING: A double-blind controlled multi-centre study
      conducted in specialist human immunodeficiency virus (HIV) care centres in Spain,
      Portugal and Australia. Participants were randomized at study entry to zidovudine
      (200 mg three times daily) plus zalcitabine (0.75 mg three times daily) or
      matched placebo. The primary end point was the proportion of patients with CD4
      above baseline value at 24 months. The secondary end points were time to
      AIDS/death, quality of life (by MOS-30) and safety. RESULTS: The study was
      terminated prematurely following the results of the Delta and ACTG 175 studies.
      Two-hundred and fifty-six patients entered the protocol of whom all but 15 were
      treatment naive. One hundred and twenty-seven patients commenced zidovudine and
      129 commenced a combination of zidovudine/zalcitabine. The median duration of
      follow-up was 634 days with a median time on blinded therapy of 500 days. Using
      the last available CD4 count data, 32.4% randomized to zidovudine and 65.1%
      randomized to zidovudine/zalcitabine remained above baseline at study close (P <
      0.001). No significant differences were observed in the time taken for CD4 count
      to return to baseline. Over 104 weeks, median CD4 counts rose in the combination
      group from 399 to 509 cells/mm3 whereas those randomized to zidovudine fell from
      410 to 374 cells/mm3. Only 12 AIDS events and two deaths (both accidental)
      occurred during the study with no differences between groups. No differences in
      quality of life were observed. Adverse events were the cause of treatment
      discontinuation in 8.6% of patients with no differences between treatment arms. A
      further 8.2% of patients were lost to follow-up. At least one adverse event (all
      severities, all relationships) was experienced by 80.3% of patients randomized to
      zidovudine and 79.8% of patients on combination. Peripheral neuropathy (all
      grades) was reported in 10.1% of patients randomized to the combination and 3. 1%
      in the zidovudine arm (P = 0.026). Oral ulcers were reported in 7.8% and 4.7% of
      combination and zidovudine monotherapy arms, respectively. Neutropenia was more
      common in the zidovudine group (22%) than the combination group (14%).
      CONCLUSIONS: Combination of zidovudine/zalcitabine as initial therapy maintains
      CD4 count above commencement levels in a significantly greater proportion of
      patients than zidovudine monotherapy. In persons with CD4 counts > or = 300
      cells/mm3 inclusion of zalcitabine with zidovudine does not increase the
      incidence of adverse events or adversely affect quality of life.

PMID- 11327443
TI  - Meta-analysis of five randomized controlled trials comparing continuation of
      zidovudine versus switching to didanosine in HIV-infected individuals.
AB  - A meta-analysis of the original data from 2411 patients in the ACTG 116A,
      ACTG116B/117, ACTG175, BMS010 and CTN002 trials was conducted to improve the
      estimate of the effect of switching from zidovudine to didanosine on rates of
      clinical progression, to better quantify the rates of neurological events
      (including AIDS dementia and peripheral neuropathy) and to examine the effects of
      switching from zidovudine to didanosine among women and racial subgroups. In
      total, 1012 patients received zidovudine therapy, 557 received high-dose
      didanosine and 842 received didanosine. The median duration of follow-up was 15
      months. Ninety-one percent of patients were male, 78% were white, mean age was
      36.5 years. The median CD4 count was 195 cells/mm3 (range: 0-762) and the median
      duration of prior zidovudine therapy was 14 months (range: 0.1-94). There were
      336 deaths and 686 new AIDS-defining illnesses (ADIs) or deaths. After
      stratification by study and adjusting for baseline CD4 count and presence of an
      AIDS diagnosis prior to baseline, the relative risks of death associated with
      switching from zidovudine to high-dose didanosine or to didanosine were 0.94 (P =
      0.64) and 0.77 (P = 0.07), respectively. The relative risks of a new ADI or death
      associated with switching from zidovudine to high-dose didanosine and didanosine
      were 0.78 (P = 0.01) and 0.66 (P = 0.0001), respectively. There were 21
      documented cases of AIDS dementia complex (ADC) during the entire follow-up
      period. The rates per 100 person years of follow-up were 0.70, 0.65 and 0.41 for
      the zidovudine, high-dose didanosine and didanosine arms, respectively. There
      were no significant differences in risks of ADC between treatment arms
      (zidovudine versus high-dose didanosine: P = 0.30, zidovudine versus didanosine:
      P = 0.97, didanosine versus high-dose didanosine: P = 0.41). Our data confirm a
      clinical benefit and CD4 increase associated with a switch from zidovudine to
      didanosine therapy. No statistical differences were detected between doses of
      didanosine with respect to survival or progression to a new ADI or death.
      Furthermore, there was no statistical difference in the frequency of ADC between
      treatment arms.

PMID- 11327444
TI  - Single dose, dose-escalating trial with fozivudine tidoxil (BM 21.1290).
AB  - BACKGROUND AND OBJECTIVES: In vitro and in vivo experimental data for fozivudine
      tidoxil [BM21.1290 (FZD) an ether-lipid conjugate of zidovudine] have shown
      better efficacy, no myelotoxicity and better tolerability compared with
      zidovudine. Therefore, the objectives of our study were to evaluate the safety of
      FZD in patients with human immunodeficiency virus (HIV) infection and to
      establish basic pharmacokinetic data. PATIENTS AND METHODS: In a Phase I dose
      escalating trial, seven different single dose applications were studied in 39
      patients: 50, 100, 300, 600, 900, 1200 and 1800 mg in capsule and tablet
      formulations. Inclusion criteria were HIV infection, CD4 count > 100 cells/mm3
      and informed consent. Exclusion criteria were active opportunistic
      manifestations, concomitant zidovudine therapy and neutropenia (< 750
      neutrophils/mm3). Safety parameters, 24 h plasma levels and urinary excretion
      were determined. RESULTS: The tolerance of FZD was excellent up to single doses
      of 1800 mg. In only one case, a single episode of loose stool was reproducible in
      a second treatment period and was therefore considered to be a probable drug
      related event. In an amendment to the trial, a tablet formulation of FZD did not
      induce diarrhoea in this patient. FZD was available in measurable concentrations
      after 2 to 4 h. Maximum concentrations were reached after 4 to 8 h. After
      normalization for a dose of 100 mg/patient, the mean AUC was 8.6 mg x h/l and the
      mean Cmax was 1.13 mg/l; t1/2 was 3.78 h. Interestingly, plasma concentrations of
      zidovudine and zidovudine glucuronide were much lower than with equimolar
      zidovudine doses. CONCLUSIONS: The zidovudine conjugate FZD is safe and well
      tolerated at the seven doses tested. Phase II trials are warranted.

PMID- 11327445
TI  - Phase I/II trial with fozivudine tidoxil (BM 21.1290): a 7 day randomized,
      placebo-controlled dose-escalating trial.
AB  - BACKGROUND AND OBJECTIVES: A Phase I dose-escalating trial with single doses of
      fozivudine tidoxil (BM21.1290; FZD), in vitro, and experimental in vivo data
      indicated that further investigations with this compound were warranted.
      Advantages of fozivudine tidoxil are the direct delivery of zidovudine
      monophosphate intracellularly and high concentrations in lymphatic tissues. Our
      objectives were to evaluate safety, tolerability and efficacy of fozivudine
      tidoxil in human immunodeficiency virus (HIV)-infected patients. PATIENTS AND
      METHODS: In a Phase I/II dose-escalating trial, three doses of fozivudine tidoxil
      (400, 800 or 1200 mg/day) were administered for 1 week. The study was randomized
      and placebo controlled. Inclusion criteria were HIV infection, CD4 count > 100
      cells/mm3 and informed consent. The exclusion criteria were active opportunistic
      infection and prior antiretroviral treatment. RESULTS: The tolerability of
      fozivudine tidoxil was excellent in all dose groups. No treatment
      discontinuations were necessary. Steady-state pharmacokinetics did show slightly
      higher concentrations as compared with levels after the first dose (20%). Viral
      load reduction was most pronounced in the 1200 mg/day dose group (-0.64 log). No
      viral load reduction was seen in the placebo group. CONCLUSIONS: The zidovudine
      conjugate fozivudine tidoxil is safe and well tolerated at the three doses
      tested. Based on the differences in molecular weights, the 1200 mg dose is
      roughly equivalent to 400 mg zidovudine.

PMID- 11327447
TI  - Microbial Genomics Workshop to help US take lead in sequencing animal pathogens.

PMID- 11327448
TI  - Government evaluates distress of laboratory animals.

PMID- 11327446
TI  - Influence of time and storage conditions on plasma HIV viral load measurements.
AB  - Quantification of human immunodeficiency virus (HIV) RNA in plasma from HIV
      infected patients is now widely used as a clinical indicator of disease prognosis
      and of response to antiretroviral therapy. However, controversy exists as to
      whether values obtained under different testing conditions could vary
      significantly, thus jeopardizing the appropriate interpretation of data. Herein,
      we demonstrate that results obtained after testing plasma versus whole blood, or
      immediate versus deferred processing, do not appear to influence viral load
      measurements significantly. Thirty blood samples from HIV-infected patients were
      analysed. The second generation branched-DNA assay was used for quantification of
      plasma viral load. HIV RNA remained stable for at least 24 h at room temperature,
      either in plasma or in whole blood, in 72.4% of the samples (< 0.2 log difference
      in viral load values) although lower levels of HIV RNA tend to be seen in samples
      after being stored as whole blood at room temperature. Only 3.4% of samples
      showed a decline > 0.5 log when they were left as whole blood at room temperature
      for 24 h in comparison with testing after immediate plasma separation. Although
      immediate separation and refrigeration of plasma samples may reduce the chance of
      significant falls in viral load measurements, this level of processing can be
      limited in regions where clinical blood samples cannot be processed rapidly. Our
      data provide confidence in the results obtained when testing specimens, either
      plasma or whole blood, 24 h after venepuncture and storage at room temperature,
      mimicking the conditions in the transport of blood samples to reference centres.

PMID- 11327449
TI  - Photoelastic stress analysis of strain patterns in equine hooves after four-point
      trimming.
AB  - OBJECTIVE: To evaluate changes in strain patterns in normal equine hooves
      following 4-point trimming, using photoelastic stress analysis. SAMPLE
      POPULATION: 15 equine front limbs with normal hoof configuration. PROCEDURE:
      Limbs were disarticulated at the carpometacarpal joint. Weight-bearing surfaces
      of each hoof were trimmed level to ensure 100% ground contact. Hoof walls were
      coated with a custom-made strain-sensitive plastic, and limbs were loaded to a
      third of body weight. Using a polariscope, strain distribution, magnitudes, and
      directions were evaluated in level hooves as well as before and after
      standardized 4-point trimming. Repeated-measures ANOVA was used to compare strain
      magnitudes and directions before and after trimming. RESULTS: In leveled
      specimens, strain fields were symmetrically distributed above the heels and at
      quarter-toe junctions along a line between the middle and distal thirds of the
      hoof wall. After 4-point trimming, strain epicenters localized above the contact
      points, whereas strain magnitudes significantly increased by approximately 50%.
      Decreasing contact area by 50% resulted in an additional significant increase
      (32%) in strain magnitude. Trimming did not have a significant effect on strain
      orientations. CONCLUSION AND CLINICAL RELEVANCE: This study documents that 4
      point trimming results in strain concentration above the hoof contact points and
      that strain magnitude is dependent on contact area.

PMID- 11327450
TI  - Determination of differential cell counts in feline bone marrow by use of flow
      cytometry.
AB  - OBJECTIVE: To evaluate the potential usefulness of 2 flow cytometric methods for
      determination of differential cell counts in feline bone marrow. SAMPLE
      POPULATION: 10 bone marrow specimens from client-owned cats. PROCEDURE: Bone
      marrow specimens were stained with 3,3'-dihexyloxacarbocyanine iodide (DiOC6) and
      evaluated by use of flow cytometry. Differential counts were also determined by
      analysis of scatterplots of forward-angle versus side-angle light scatter of
      unstained specimens, obtained by use of flow cytometry (scatterplot method).
      Results of both flow cytometric methods were compared with differential cell
      counts determined by manually counting 1,000 cells on slides of Wright-stained
      smears. RESULTS: Staining with DiOC6 resulted in identification of mature and
      immature erythroid and myeloid cells and lymphocytes. Use of the scatterplot
      method resulted in identification of mature and immature erythroid and myeloid
      cells and metamyelocytes. However, to identify lymphocytes by use of the
      scatterplot method, bone marrow specimens were first labeled with an anti-major
      histocompatability class-II antibody. Comparison of results of the scatterplot
      method with manual counts yielded higher correlation coefficients and more
      similar mean values than did comparison of results of the DiOC6 method.
      CONCLUSIONS AND CLINICAL RELEVANCE: The scatterplot method provided more accurate
      and precise results than the DiOC6 method for determination of bone marrow
      differential cell counts in cats by use of flow cytometry. When combined with
      fluorescent labeling of lymphocytes, the scatterplot method has potential to
      provide rapid semiquantitative assessment of bone marrow differential cell counts
      in cats.

PMID- 11327451
TI  - Density of corneal endothelial cells and corneal thickness in eyes of
      euthanatized horses.
AB  - OBJECTIVE: To determine density of corneal endothelial cells and corneal
      thickness in eyes of euthanatized horses. SAMPLE POPULATION: 52 normal eyes from
      26 horses. PROCEDURE: Eyes were enucleated after horses were euthanatized. Eyes
      were examined to determine that they did not have visible ocular defects.
      Noncontact specular microscopy was used to determine density of corneal
      endothelial cells. Corneal thickness was measured, using ultrasonic pachymetry or
      specular microscopy. RESULTS: Mean density of corneal endothelial cells was 3,155
      cells/mm2. Cell density decreased with age, but sex did not affect cell density.
      Values did not differ significantly between right and left eyes from the same
      horse. Cell density of the ventral quadrant was significantly less than cell
      density of the medial and temporal quadrants. Mean corneal thickness was 893
      microm. Sex or age did not affect corneal thickness. Dorsal and ventral quadrants
      were significantly thicker than the medial and temporal quadrants and central
      portion of the cornea. We did not detect a correlation between corneal thickness
      and density of endothelial cells in normal eyes of horses. CONCLUSIONS AND
      CLINICAL RELEVANCE: Density of corneal endothelial cells decreases with age, but
      corneal thickness is not affected by age or sex in normal eyes of horses. The
      technique described here may be useful for determining density of endothelial
      cells in the cornea of enucleated eyes. This is clinically relevant for analyzing
      corneal donor tissue prior to harvest and use for corneal transplantation.

PMID- 11327452
TI  - Disposition, elimination, and bioavailability of phenytoin and its major
      metabolite in horses.
AB  - OBJECTIVE: To determine pharmacokinetics and excretion of phenytoin in horses.
      ANIMALS: 6 adult horses. PROCEDURE: Using a crossover design, phenytoin was
      administered (8.8 mg/kg of body weight, IV and PO) to 6 horses to determine
      bioavailability (F). Phenytoin also was administered orally twice daily for 5
      days to those same 6 horses to determine steady-state concentrations and
      excretion patterns. Blood and urine samples were collected for analysis. RESULTS:
      Mean (+/- SD) elimination half-life following a single IV or PO administration
      was 12.6+/-2.8 and 13.9+/-6.3 hours, respectively, and was 11.2+/-4.0 hours
      following twice-daily administration for 5 days. Values for F ranged from 14.5 to
      84.7%. Mean peak plasma concentration (Cmax) following single oral administration
      was 1.8+/-0.68 microg/ml. Steady-state plasma concentrations following twice
      daily administration for 5 days was 4.0+/-1.8 microg/ml. Of the 12.0+/-5.4% of
      the drug excreted during the 36-hour collection period, 0.78+/-0.39% was the
      parent drug phenytoin, and 11.2+/-5.3% was 5-(phydroxyphenyl)-5-phenylhydantoin
      (p-HPPH). Following twice-daily administration for 5 days, phenytoin was
      quantified in plasma and urine for up to 72 and 96 hours, respectively, and p
      HPPH was quantified in urine for up to 144 hours after administration. This
      excretion pattern was not consistent in all horses. CONCLUSIONS AND CLINICAL
      RELEVANCE: Variability in F, terminal elimination-phase half-life, and Cmax
      following single or multiple oral administration of phenytoin was considerable.
      This variability makes it difficult to predict plasma concentrations in horses
      after phenytoin administration.

PMID- 11327453
TI  - Cardiovascular effects of romifidine in dogs.
AB  - OBJECTIVE: To characterize the cardiovascular effects of romifidine at doses
      ranging from 5 to 100 microg/kg of body weight, IV. ANIMALS: 25 clinically normal
      male Beagles. PROCEDURE: Romifidine was administered IV at a dose of 5, 10, 25,
      50, or 100 microg/kg (n = 5/group). Heart rate, arterial pressure, central venous
      pressure, mean pulmonary arterial pressure, pulmonary capillary wedge pressure,
      body temperature, cardiac output, and PCV were measured immediately prior to and
      at selected times after romifidine administration. Cardiac index, stroke index,
      rate-pressure product, systemic and pulmonary vascular resistance indices, and
      left and right ventricular stroke work indices were calculated. Degree of
      sedation was assessed by an observer who was blinded to the dose administered.
      RESULTS: Romifidine induced a decrease in heart rate, pulmonary arterial
      pressure, rate-pressure product, cardiac index, and right ventricular stroke work
      index and an increase in central venous pressure, pulmonary capillary wedge
      pressure, and systemic vascular resistance index. In dogs given romifidine at a
      dose of 25, 50, or 100 microg/kg, an initial increase followed by a prolonged
      decrease in arterial pressure was observed. Arterial pressure immediately
      decreased in dogs given romifidine at a dose of 5 or 10 microg/kg. CONCLUSIONS
      AND CLINICAL RELEVANCE: Results suggest that IV administration of romifidine
      induces dose-dependent cardiovascular changes in dogs. However, the 2 lowest
      doses (5 and 10 microg/kg) induced less cardiovascular depression, and doses > or
      = 25 microg/kg induced similar cardiovascular changes, suggesting that there may
      be a ceiling on the cardiovascular effects of romifidine.

PMID- 11327454
TI  - Effect of centrally administered opioid receptor agonists on CSF and plasma
      oxytocin concentrations in dogs.
AB  - OBJECTIVE: To measure oxytocin concentrations in blood and CSF following central
      administration of opioid agonists in dogs. ANIMALS: 5 male dogs. PROCEDURE: In a
      crossover design, CSF and blood were collected immediately before and 15 and 30
      minutes after cisternal administration of D-Ala2, MePhe4, Gly-ol-enkephalin
      (DAMGO, a mu-receptor agonist); D-Pen, pCl-Phe4, D-Pen5-enkephalin (a delta
      receptor agonist); U50488H (a kappa-receptor agonist); morphine; and saline (0.9%
      NaCl) solution. RESULTS: Plasma oxytocin concentration was significantly
      increased 15 minutes after administration of DAMGO and 30 minutes after
      administration of U50488H, compared with concentrations obtained after
      administration of saline solution. Concentration of oxytocin in CSF was
      significantly decreased 30 minutes after administration of U50488H, compared with
      concentration after administration of saline solution. CONCLUSIONS AND CLINICAL
      RELEVANCE: Results suggest that in male dogs, activation of centrally located mu
      and kappa receptors elicits an overall excitatory effect on neurons that regulate
      peripheral release of oxytocin, whereas activation of centrally located kappa
      receptors elicits an overall inhibitory effect on neurons that regulate central
      release. These results are in contrast to those reported for other species, in
      which opioids have a pronounced inhibitory effect on release of oxytocin from the
      neurohypophysis.

PMID- 11327455
TI  - Infusion of a combination of propofol and medetomidine for long-term anesthesia
      in ponies.
AB  - OBJECTIVE: To determine the minimal infusion rate of propofol in combination with
      medetomidine for long-term anesthesia in ponies and the effects of atipamezole on
      recovery. ANIMALS: 12 ponies. PROCEDURE: Ponies were sedated with medetomidine (7
      microg/kg of body weight, IV). Ten minutes later, anesthesia was induced with
      propofol (2 mg/kg, IV). Anesthesia was maintained for 4 hours, using an infusion
      of medetomidine (3.5 microg/kg per hour, IV) and propofol at a rate sufficient to
      prevent ponies from moving after electrical stimulation. Arterial blood pressures
      and blood gas analysis, heart rates, and respiratory rates were monitored. For
      recovery, 6 ponies were given atipamezole (60 microg/kg, IV). Induction and
      recovery were scored. RESULTS: Minimal propofol infusion rates ranged from 0.06
      to 0.1 mg/kg per min. Mean arterial blood pressure was stable (range, 74 to 86 mm
      Hg), and heart rate (34 to 51 beats/min) had minimal variations. Variable
      breathing patterns were observed. Mean PaO2 (range, 116 to 146 mm Hg) and mean
      PaCO2 (range, 48 to 51 mm Hg) did not change significantly with time, but
      hypoxemia was evident in some ponies (minimal PaO2, 47 mm Hg). Recovery was fast
      and uneventful with and without atipamezole (completed in 20.2 and 20.9 minutes,
      respectively). CONCLUSIONS AND CLINICAL RELEVANCE: Infusion of a combination of
      medetomidine and propofol was suitable for prolonged anesthesia in ponies.
      Recovery was rapid and uneventful. A combination of propofol and medetomidine may
      prove suitable for long-term anesthesia in horses. Monitoring of blood gases is
      essential because of potential hypoxemia.

PMID- 11327457
TI  - Contact transmission of vesicular stomatitis virus New Jersey in pigs.
AB  - OBJECTIVE: To determine how viral shedding and development or lack of clinical
      disease relate to contact transmission of vesicular stomatitis virus New Jersey
      (VSV-NJ) in pigs and determine whether pigs infected by contact could infect
      other pigs by contact. ANIMALS: 63 pigs. PROCEDURE: Serologically naive pigs were
      housed in direct contact with pigs that were experimentally inoculated with VSV
      NJ via ID inoculation of the apex of the snout, application to a scarified area
      of the oral mucosa, application to intact oral mucosa, or ID inoculation of the
      ear. In a second experiment, pigs infected with VSV-NJ by contact were moved and
      housed with additional naive pigs. Pigs were monitored and sampled daily for
      clinical disease and virus isolation and were serologically tested before and
      after infection or contact. RESULTS: Contact transmission developed only when
      vesicular lesions were evident. Transmission developed rapidly; contact pigs shed
      virus as early as 1 day after contact. In pens in which contact transmission was
      detected, 2 of 3 or 3 of 3 contact pigs were infected. CONCLUSIONS AND CLINICAL
      RELEVANCE: Transmission was lesion-dependent; however, vesicular lesions often
      were subtle with few or no clinical signs of infection. Contact transmission was
      efficient, with resulting infections ranging from subclinical (detected only by
      seroconversion) to clinical (development of vesicular lesions). Long-term
      maintenance of VSV-NJ via contact transmission alone appears unlikely. Pigs
      represent an efficient large-animal system for further study of VSV-NJ
      pathogenesis and transmission.

PMID- 11327456
TI  - Generation of reactive oxygen species by equine spermatozoa.
AB  - OBJECTIVE: To characterize generation of reactive oxygen species (ROS) by equine
      spermatozoa. SAMPLE POPULATION: Multiple semen samples collected from 9
      stallions. PROCEDURE: Equine spermatozoa were separated from seminal plasma on a
      discontinuous polyvinylpyrrolidone (PVP)-coated silica gradient and resuspended
      in a modified Tyrode albumin-lactate-pyruvate medium. Amount of hydrogen peroxide
      (H2O2) generated was assayed by use of a 1-step fluorometric assay, using 10
      acetyl-3,7-dihydroxyphenoxazine as a probe for detection of H2O2 in a microplate
      assay format. Concentration of H2O2 was determined by use of a fluorescence
      microplate reader. RESULTS: Amount of H2O2 generated increased significantly with
      time and spermatozoa concentration for live and flash-frozen spermatozoa, and
      amount of H2O2 generated was significantly greater for flash-frozen than for live
      spermatozoa. Addition of the reduced form of nicotinamide adenine dinucleotide
      phosphate (NADPH) significantly increased generation of H2O2 by live and flash
      frozen spermatozoa. Addition of a calcium ionophore also significantly increased
      the amount of H2O2 generated by live spermatozoa but did not have an effect on
      amount of H2O2 generated by flash-frozen spermatozoa. Abnormal equine spermatozoa
      generated significantly greater amounts of H2O2 than did normal spermatozoa.
      CONCLUSIONS AND CLINICAL RELEVANCE: Equine spermatozoa generate ROS in vitro,
      possibly via a NADPH-oxidase reaction. Spermatozoa damaged during flash-freezing
      or morphologically abnormal spermatozoa generated significantly greater amounts
      of ROS than did live or morphologically normal spermatozoa. Damaged and abnormal
      spermatozoa generate greater amounts of ROS that may contribute to reduced
      fertility or problems related to semen preservation.

PMID- 11327458
TI  - Effects of intranasal inoculation with Bordetella bronchiseptica, porcine
      reproductive and respiratory syndrome virus, or a combination of both organisms
      on subsequent infection with Pasteurella multocida in pigs.
AB  - OBJECTIVE: To determine effects of intranasal inoculation with porcine
      reproductive and respiratory syndrome virus (PRRSV) or Bordetella bronchiseptica
      on challenge with nontoxigenic Pasteurella multocida in pigs. ANIMALS: Seventy 3
      week-old pigs. PROCEDURE: In experiment 1, pigs were not inoculated (n= 10) or
      were inoculated with PRRSV (10), P. multocida (10), or PRRSV followed by
      challenge with P. multocida (10). In experiment 2, pigs were not inoculated (n =
      10) or were inoculated with B. bronchiseptica (10) or PRRSV and B. bronchiseptica
      (10); all pigs were challenged with P. multocida. Five pigs from each group were
      necropsied 14 and 21 days after initial inoculations. RESULTS: Pasteurella
      multocida was not isolated from tissue specimens of pigs challenged with P.
      multocida alone or after inoculation with PRRSV. However, in pigs challenged
      after inoculation with B. bronchiseptica, P. multocida was isolated from
      specimens of the nasal cavity and tonsil of the soft palate. Number of bacteria
      isolated increased in pigs challenged after coinoculation with PRRSV and B.
      bronchiseptica, and all 3 agents were isolated from pneumonic lesions in these
      pigs. CONCLUSIONS AND CLINICAL RELEVANCE: Infection of pigs with B.
      bronchiseptica but not PRRSV prior to challenge with P. multocida resulted in
      colonization of the upper respiratory tract and tonsil of the soft palate with P.
      multocida. Coinfection with PRRSV and B. bronchiseptica predisposed pigs to
      infection of the upper respiratory tract and lung with P. multocida. Porcine
      reproductive and respiratory syndrome virus and B. bronchiseptica may interact to
      adversely affect respiratory tract defense mechanisms, leaving pigs especially
      vulnerable to infection with secondary agents such as P. multocida.

PMID- 11327459
TI  - Microvascular development and growth of uterine tissue during the estrous cycle
      in mares.
AB  - OBJECTIVE: To document uterine growth and microvascular development in the
      endometrium of uteri with differing degrees of fibrosis as well as uterine growth
      throughout the estrous cycle of mares. ANIMALS: 30 mares. PROCEDURE: Uterine
      tissue was obtained during the breeding season from a slaughter facility. Stage
      of estrous cycle of the mares was assessed on the basis of ovarian structures and
      plasma progesterone concentrations. Endometrium was characterized by use of light
      microscopy, and blood vessel walls were marked by histochemical techniques.
      Microvascular development was evaluated by a computerized image analysis system.
      Growth of uterine tissue was based on cellular content of DNA and RNA, RNA:DNA,
      and protein:DNA. RESULTS: Significant differences in vascular density were not
      observed in the endometrium of uteri obtained from mares euthanatized during the
      follicular or luteal phase of the estrous cycle, regardless of whether
      endometrial classification of degree of fibrosis was considered. There was a 3
      fold increase in amount of DNA and RNA of endometrial cells in the follicular
      phase when compared to myometrium. Hypertrophy of endometrial tissue during the
      luteal phase was reflected by a significant increase in cell protein content and
      protein:DNA. CONCLUSIONS AND CLINICAL RELEVANCE: Endometrial growth of vascular
      tissues during the estrous cycle may be coordinated with development of
      nonvascular tissue. Estrogen and progesterone may play a role in regulation of
      uterine growth and angiogenesis.

PMID- 11327460
TI  - Neodymium:yttrium aluminum garnet laser ventriculocordectomy in standing horses.
AB  - OBJECTIVE: To develop a technique for neodymium:yttrium-aluminum-garnet (Nd:YAG)
      laser ventriculocordectomy in standing horses and document healing in horses
      undergoing laser ventriculocordectomy. ANIMALS: 6 horses between 2 and 32 years
      old. PROCEDURE: Under endoscopic guidance, the left laryngeal ventricle was
      everted with grasping forceps and excised with an Nd:YAG laser, using 60 watts of
      power in a noncontact fashion (6,403 to 9,197 Joules). Following removal of the
      ventricle, the vocal cord was photoablated. Horses were examined endoscopically
      2, 7, 14, 21, 30, and 47 days after ventriculocordectomy, and 1 horse was
      euthanatized on each of these days. At necropsy, the larynx was removed intact
      and examined grossly. Samples were collected for histologic examination of the
      ventriculocordectomy site. RESULTS: Endoscopic examination revealed granulation
      tissue by day 7, the start of epithelialization by day 21, and healing by day 47.
      At necropsy, 4 horses were found to have a small amount of ventricular mucosa
      remaining dorsally and 1 additional horse was found to have a mucocele.
      Granulation tissue was identified grossly and histologically in the horses
      euthanatized between 7 and 30 days after surgery. Incipient reepithelialization
      was evident histologically on day 14, and complete reepithelialization of the
      surgery site was evident by day 47. CONCLUSION AND CLINICAL RELEVANCE: Results
      suggest that ventriculocordectomy can safely be performed with an Nd:YAG laser in
      standing horses.

PMID- 11327461
TI  - Clinical signs, evaluation of bronchoalveolar lavage fluid, and assessment of
      pulmonary function in horses with inflammatory respiratory disease.
AB  - OBJECTIVE: To evaluate the association among clinical signs, results of cytologic
      evaluation of bronchoalveolar lavage (BAL) fluid, and measures of pulmonary
      function in horses with inflammatory respiratory disease. ANIMALS: 9 healthy
      horses, 5 horses with inflammatory airway disease (IAD), and 9 horses with
      chronic obstructive pulmonary disease (COPD). PROCEDURES: Clinical examination,
      lung function tests, and BAL were performed on each horse. RESULTS: Standard lung
      mechanics of horses with exacerbated COPD differed significantly from those of
      healthy horses; however, there were few differences among horses with IAD, horses
      with COPD during remission, and healthy horses. Most variables for forced
      expiration (FE) in horses with COPD or IAD differed significantly from those for
      healthy horses. Results of clinical examination had low to moderate sensitivity
      and predictive values for a diagnosis of COPD (range, 67 to 80%). Results of FE
      tests had high sensitivity, specificity, and predictive values for a diagnosis of
      COPD (79 to 100%), and results of standard lung mechanics tests had low
      sensitivity and predictive values (22 to 69%). Percentage of neutrophils in BAL
      fluid was highly sensitive (100%) but moderately specific (64%) for a diagnosis
      of COPD. CONCLUSIONS AND CLINICAL RELEVANCE: Clinical examination is moderately
      accurate for establishing a diagnosis of COPD. Forced expiration tests can
      specifically detect early signs of airway obstruction in horses with COPD and IAD
      that may otherwise be inapparent. Cytologic evaluation of BAL fluid allows early
      detection of inflammatory respiratory disease, but it is not specific for COPD.

PMID- 11327462
TI  - Effects of sodium citrate, low molecular weight heparin, and prostaglandin E1 on
      aggregation, fibrinogen binding, and enumeration of equine platelets.
AB  - OBJECTIVE: To investigate the effects of sodium citrate, low molecular weight
      heparin (LMWH), and prostaglandin E1 (PGE1) on aggregation, fibrinogen binding,
      and enumeration of equine platelets. SAMPLE POPULATION: Blood samples obtained
      from 4 Thoroughbreds. PROCEDURE: Blood was collected into syringes in the ratio
      of 9 parts blood:1 part anticoagulant. Anticoagulants used were sodium citrate,
      LMWH, sodium citrate and LMWH, or 300 nM PGE1/ml of anticoagulant. Platelet
      aggregation in response to ADP, collagen, and PGE1 was assessed, using optical
      aggregometry. Platelet activation was evaluated, using flow cytometry, to detect
      binding of fluorescein-conjugated anti-human fibrinogen antibody. Plasma
      concentration of ionized calcium was measured, using an ion-selective electrode.
      RESULTS: Number of platelets (mean +/- SEM) in samples containing LMWH (109.5+/
      11.3 x 10(3) cells/microl) was significantly less than the number in samples
      containing sodium citrate (187.3+/-30.3 x 10(3) cells/microl). Increasing
      concentrations of sodium citrate resulted in reductions in platelet aggregation
      and plasma concentration of ionized calcium. Addition of PGE1 prior to addition
      of an agonist inhibited platelet aggregation in a concentration-dependent manner,
      whereas addition of PGE1 4 minutes after addition of ADP resulted in partial
      reversal of aggregation and fibrinogen binding. CONCLUSIONS AND CLINICAL
      RELEVANCE: A high concentration of sodium citrate in blood samples decreases
      plasma concentration of ionized calcium, resulting in reduced platelet
      aggregation and fibrinogen binding. Platelets tend to clump in samples collected
      into LMWH, precluding its use as an anticoagulant. Platelet aggregation and
      fibrinogen binding can be reversed by PGE1, which may result in underestimation
      of platelet activation.

PMID- 11327463
TI  - Effects of diazepam and flumazenil on minimum alveolar concentrations for dogs
      anesthetized with isoflurane or a combination of isoflurane and fentanyl.
AB  - OBJECTIVE: To determine the effect of a constant-rate infusion of fentanyl on
      minimum alveolar concentration (MAC) of isoflurane and to determine the
      interaction between fentanyl and a benzodiazepine agonist (diazepam) and
      antagonist (flumazenil) in isoflurane-anesthetized dogs. ANIMALS: 8 mixed-breed
      adult dogs. PROCEDURE: Dogs were anesthetized with isoflurane 3 times during a 6
      week period. After a 30-minute equilibration period, each MAC determination was
      performed in triplicate, using standard techniques. Fentanyl was administered as
      a bolus (10 microg/kg of body weight, IV) that was followed by a constant
      infusion (0.3 microg/kg per min, IV) throughout the remainder of the experiment.
      After determining isoflurane-fentanyl MAC in triplicate, each dog received saline
      (0.9% NaCl) solution, diazepam, or flumazenil. After 30 minutes, MAC was
      determined again. RESULTS: Fentanyl significantly decreased isoflurane MAC
      (corrected to a barometric pressure of 760 mm Hg) from 1.80+/-0.21 to 0.85+/
      0.14%, a reduction of 53%. Isoflurane-fentanyl-diazepam MAC (0.48+/-0.29%) was
      significantly less than isoflurane-fentanyl-saline MAC (0.79+/-0.21%). Percentage
      reduction in isoflurane MAC was significantly greater for fentanyl-diazepam
      (74%), compared with fentanyl-saline (54%) or fentanyl-flumazenil (61%). Mean
      fentanyl concentrations for the entire experiment were increased over time and
      were higher in the diazepam group than the saline or flumazenil groups.
      CONCLUSIONS AND CLINICAL RELEVANCE: Fentanyl markedly decreased isoflurane MAC in
      dogs. Diazepam, but not flumazenil, further decreased isoflurane-fentanyl MAC.
      Our results indicate that diazepam enhances, whereas flumazenil does not affect,
      opioid-induced CNS depression and, possibly, analgesia in dogs.

PMID- 11327464
TI  - Impact of environmental temperature on response of neonatal pigs to an endotoxin
      challenge.
AB  - OBJECTIVE: To evaluate the effect of various environmental temperatures (ET) on
      the ability of neonatal pigs to cope with an endotoxin challenge. ANIMALS: 28
      crossbred male pigs that were 24 hours old. PROCEDURE: At 24 hours of age, pigs
      were placed in environmentally controlled chambers maintained at 18 or 34 C (14
      pigs/ET). Rectal temperatures (RT) were recorded at 15-minute intervals for 3
      hours following an IP injection of 0.9% NaCl (7 control pigs/ET) or
      lipopolysaccharide (LPS; 150 microg/kg of body weight; 7 LPS-treated pigs/ET).
      Tissue specimens and blood samples were collected following the 3-hour challenge
      period. RESULTS: LPS-treated pigs exposed to 18 C had a period of hypothermia
      whereas RT for LPS-treated pigs at 34 C did not differ from control pigs. The LPS
      treated pigs maintained at 18 C lost the most body weight during the 3-hour
      period and also had the greatest increase in serum cortisol concentration. Serum
      prolactin (PRL) concentration was decreased in pigs at 18 C, compared with pigs
      at 34 C. Challenge with LPS resulted in an increase in serum PRL concentration at
      18 C but had no effect on serum PRL at 34 C. Challenge with LPS resulted in an
      increase in expression of tumor necrosis factor-alpha, interleukin-1 beta, and
      interleukin-6 receptor mRNA in the hypothalamus. CONCLUSIONS AND CLINICAL
      RELEVANCE: Exposure to a cold ET can inhibit the ability of neonatal pigs to cope
      with an exogenous endotoxin challenge. When combined, cold stress and exposure to
      exogenous endotoxin induces a rapid and potentially dangerous loss of body
      temperature in neonatal pigs.

PMID- 11327465
TI  - Evaluation of a nonradioactive colorimetric assay for analysis of lymphocyte
      proliferation in healthy cats.
AB  - OBJECTIVES: To compare results of a nonradioactive colorimetric microplate assay
      with results of a traditional radioactive proliferation assay for determination
      of its use as a reliable and accurate alternative method for determination of
      proliferative activity of feline lymphocytes. SAMPLE POPULATION: Blood samples
      from 10 clinically normal domestic shorthair cats. PROCEDURE: Double-density
      gradient separation was used to isolate mononuclear cells. Isolated cells were
      stimulated with various concentrations of concanavalin A (Con-A) and cultured for
      72 hours. Lymphocyte proliferation was measured by radioactive ([3H]thymidine)
      and nonradioactive (colorimetric) techniques. Immunophenotypic analysis with
      feline-specific CD4+ and CD8+ monoclonal antibody was performed, using flow
      cytometry. RESULTS: Mononuclear cells were successfully isolated (97 to 99%
      purity and viability) from blood samples. A similar dose-dependent proliferative
      response to Con-A stimulation was measured with [3H]thymidine incorporation and
      the colorimetric assay. For both techniques, concentrations of 0.1 and 1.0 microg
      of Con-A/ml were submitogenic, and 100 microg/ml was toxic to cultured cells. For
      both techniques, maximal proliferation was observed with 5 microg of Con-A/ml.
      CONCLUSIONS AND CLINICAL RELEVANCE: These results indicate that the
      nonradioactive colorimetric technique is a reliable and accurate method for
      measuring proliferative activity of feline lymphocytes. Clinically, this assay
      can be used as part of a screening process to determine immunocompetence of at
      risk cats and to evaluate treatments for cats with immune-mediated or T-cell
      dependent diseases.

PMID- 11327466
TI  - Use of plasma clearance of iohexol for estimating glomerular filtration rate in
      cats.
AB  - OBJECTIVE: To determine whether plasma clearance of iohexol (PCio) can be used to
      estimate glomerular filtration rate (GFR) in cats. ANIMALS: 4 renal-intact and 6
      partially nephrectomized adult cats. PROCEDURE: Plasma clearance of iohexol was
      determined after IV administration of iohexol; plasma concentrations of iodine
      were measured by use of a colorimetric assay. Results for PCio were compared with
      simultaneously obtained values for urinary clearance of creatinine (CCr).
      RESULTS: The colorimetric assay used to measure plasma iodine concentrations was
      extremely precise. Results of PCio for all cats, renal-intact cats, and partially
      nephrectomized cats were closely associated with results of CCr. Mean difference
      between CCr and PCio determined for all cats was 0.95 ml/min/kg, which was < 30%
      of mean CCr for renal-intact cats. Coefficients of variance for PCio (5%) and CCr
      (8%) in renal-intact cats were similar. CONCLUSIONS AND CLINICAL RELEVANCE:
      Plasma clearance of iohexol determined by use of a simple colorimetric assay
      provided an estimation of GFR in cats that was not significantly different from
      that provided by CCr. Moreover, PCio more reliably estimates renal function than
      BUN and plasma creatinine concentrations. Because determination of PCio is less
      labor intensive and invasive, compared with CCr, it may be easier to perform in a
      clinical setting.

PMID- 11327467
TI  - Influence of an interdental full pin on stability of an acrylic external fixator
      for rostral mandibular fractures in dogs.
AB  - OBJECTIVE: To determine total stiffness and gap stiffness of an external fixation
      system in a canine mandibular fracture gap model incorporating a full interdental
      pin as the only point of rostral fixation in a bilateral type-I external fixator.
      SAMPLE POPULATION: 10 canine mandibles. PROCEDURE: Bilateral mandibular
      ostectomies were performed between premolars 3 and 4. A type-I external fixator
      incorporating a full interdental pin was placed to stabilize a 0.5-cm fracture
      gap. Four pin configurations (intact mandibular bodies with fixator; ostectomized
      mandibular bodies and complete fixator; ostectomized mandibular bodies with
      caudal pins of rostral fragment cut; ostectomized mandibular bodies with all pins
      of rostral fragment cut) were tested in dorsoventral bending 5 times on each
      mandible. The full interdental pin remained intact in all configurations. Total
      stiffness and gap stiffness were determined for each configuration on a materials
      testing machine. RESULTS: Total stiffness of intact mandibles was significantly
      greater than that of ostectomized mandibles, regardless of external fixator
      configuration. However, total stiffness and gap stiffness were not significantly
      different among different external fixator configurations applied to ostectomized
      mandibles. CONCLUSION AND CLINICAL RELEVANCE: External fixator configurations
      with only the full interdental pin engaging the rostral fragment were as stiff as
      configurations that had 2 or 4 additional pins in the rostral fragment for the
      applied loads. External fixators for rostral mandibular fractures may be rigidly
      secured with rostral fragment implants applied extracortically, avoiding
      iatrogenic trauma to teeth and tooth roots.

PMID- 11327468
TI  - Concentrations of chondroitin sulfate epitopes 3B3 and 7D4 in synovial fluid
      after intra-articular and extracapsular reconstruction of the cranial cruciate
      ligament in dogs.
AB  - OBJECTIVE: To evaluate effects of intra-articular and extracapsular
      reconstruction of the cranial cruciate ligament (CCL) on metabolism of articular
      cartilage as reflected by concentrations of chondroitin sulfate epitopes 3B3 and
      7D4 in synovial fluid. ANIMALS: 13 adult dogs. PROCEDURE: Each dog underwent
      unilateral CCL transection (CCLT). One month after CCLT, sham CCL reconstruction
      (3 dogs), intra-articular CCL reconstruction (5), or extracapsular CCL
      reconstruction (5) was performed. Synovial fluid was collected by direct
      arthrocentesis from CCLT and contralateral stifle joints immediately before (time
      0) and 1, 3, and 5 months after CCLT. Fluid was examined for concentrations of
      3B3 and 7D4 epitopes and total sulfated glycosaminoglycan (GAG) content. RESULTS:
      Concentrations of 3B3, 7D4, and GAG, 3B3:GAG, or 7D4:GAG in CCLT joints did not
      differ significantly among treatment groups nor in the ratios of these variables
      in CCLT joints to contralateral joints at 3 months. In a longitudinal analysis,
      concentrations of 3B3 and 7D4, 3B3:GAG, and 7D4:GAG in CCLT joints in all groups
      changed significantly with time, but we did not detect time X group interactions.
      CONCLUSIONS AND CLINICAL RELEVANCE: Transection of CCL resulted in significant
      perturbation in articular cartilage metabolism as reflected by alterations in
      concentrations of 3B3 and 7D4 in synovial fluid. These changes over time were not
      significantly influenced by method of CCL reconstruction. We did not find
      evidence that surgical stabilization of CCL-deficient joints by intra-articular
      or extracapsular techniques had any effect on preventing alterations in
      composition of synovial fluid that have been associated with secondary
      osteoarthritis.

PMID- 11327470
TI  - Amidolytic heparin activity and values for several hemostatic variables after
      repeated subcutaneous administration of high doses of a low molecular weight
      heparin in healthy dogs.
AB  - OBJECTIVE: To determine effects of SC administration of repeated doses of a low
      molecular weight heparin (LMWH) in dogs. ANIMALS: 5 healthy dogs. PROCEDURE: Each
      dog received 6 injections (each injection, 150 U of anti-factor-Xa [anti-FXal/kg
      of body weight, SC) at 8-hour intervals. Blood samples were collected before and
      2 hours after the first, second, third, and sixth injections to measure heparin
      activity, thrombin time, activated partial thromboplastin time (APTT),
      antithrombin activity, Hct, and platelet count. RESULTS: Heparin activity varied
      between 0.36+/-0.10 and 0.77+/-0.08 U of anti-FXa/ml (before and 2 hours after
      the third injection) and between 0.46+/-0.11 and 0.82+/-0.15 U of anti-FXa/ml
      (before and 2 hours after the sixth injection). Thrombin time and APTT were
      influenced only slightly. Platelet count, Hct, and antithrombin activity started
      to decrease significantly 2 hours after the second LMWH injection. Because of the
      increased consumption of antithrombin, antithrombin activity continuously
      decreased from 102.1+/-6.3% before the study to 91.0+/-3.0% at the end of the
      study. CONCLUSIONS AND CLINICAL RELEVANCE: Heparin plasma activity was only
      slightly higher than that recommended for LMWH treatment of humans, and none of
      the dogs had signs of increased bleeding. Thus, administration of heparin in
      accordance with this dosing regimen can be recommended for use in clinical
      studies. The screening tests investigated were not suitable for use in monitoring
      LMWH treatment of dogs. Assays that use chromogenic substrates are necessary to
      reliably monitor LMWH plasma concentrations in dogs.

PMID- 11327469
TI  - In vitro characterization of FIV-pPPR, a pathogenic molecular clone of feline
      immunodeficiency virus, and two drug-resistant pol gene mutants.
AB  - OBJECTIVE: To compare in vitro replication kinetics and nucleoside analog
      susceptibilities of a natural feline immunodeficiency virus (FIV) isolate (FIV
      Maxam), a molecular clone of FIV (FIV-pPPR), and two (-)-beta-L-2',3'-dideoxy-3'
      thiacytidine- (3TC-) resistant mutants of FIV-pPPR. SAMPLE POPULATION: Peripheral
      blood mononuclear cells (PBMC) from 4 specific-pathogenfree cats. PROCEDURE: Two
      point mutations corresponding to mutations of human immunodeficiency virus type 1
      (HIV-1) were engineered into the highly conserved YMDD motif of the reverse
      transcriptase- (RT-) encoding region of the FIV-pPPR pol gene. Replication
      kinetics and nucleoside analog susceptibilities of FIV-Maxam, FIV-pPPR, and the 2
      mutant viruses were measured in vitro, using feline PBMC. RESULTS: Replication
      kinetics and nucleoside analog susceptibilities were similar between FIV-Maxam
      and FIV-pPPR. However, FIV-Maxam was significantly more susceptible to 3TC. A
      methionine-to-valine mutation at codon 183 (M183V) of the RT-encoding region of
      the pol gene of FIV-pPPR conferred high-level phenotypic resistance to 3TC and
      cross-resistance to the related compound (-)-beta-L-2',3'-dideoxy-5-fluoro-3'
      thiacytidine. CONCLUSIONS AND CLINICAL RELEVANCE: Similarities between FIV-Maxam
      and FIV-pPPR suggest that results of studies performed using FIV-pPPR will have
      relevance to natural FIV infection in cats. In vitro evaluation of nucleoside
      analog susceptibilities of FIV-Maxam may help determine concentrations of
      nucleoside analogs required for effective treatment of FIV-infected cats. IMPACT
      FOR HUMAN MEDICINE: 3TC resistance of FIV-pPPR M183V was similar in magnitude to
      that of HIV-1 M184V, a mutant described in infected humans treated with 3TC.
      Thus, FIV-pPPR M183V may be a useful model for studying the in vivo effects of
      3TC resistance on lentivirus pathogenesis.

PMID- 11327472
TI  - Use of a polymerase chain reaction assay to detect and differentiate two strains
      of Haemobartonella felis in naturally infected cats.
AB  - OBJECTIVE: To develop a polymerase chain reaction (PCR) assay that detects and
      differentiates the Ohio strain of Haemobartonella felis (H. felis-OH) and the
      California strain of H. felis (H. felis-CA) and to apply the assay to blood
      samples from cats with and without suspected haemobartonellosis (suspect and
      control cats, respectively). SAMPLE POPULATION: 220 blood samples were examined;
      82 were from suspect cats, and 138 were from control cats. PROCEDURE: A PCR assay
      was designed to detect and differentiate H. felis-OH and H. felis-CA. RESULTS: On
      the basis of PCR assay results, the overall prevalence of H. felis infection was
      19.5% (43/220). Suspect cats (28.0%; 23/82) were significantly more likely than
      control cats (14.5%; 20/138) to be H. felis infected. Significantly greater
      numbers of suspect cats were H. felis-OH infected (12.2%, 9/82) or H. felis-OH
      and H. felis-CA infected (4.9%, 4/82) than control cats (0% [0/138] and 0.7%
      [1/138], respectively). Significantly more anemic cats were H. felis-OH infected
      (14.3%; 4/28) or H. felis-OH and H. felis-CA infected (7.1%; 2/28) than nonanemic
      cats (2.3% [3/128] and 0.8% [1/128], respectively). The PCR assay was more
      accurate than cytologic examination for detection of H. felis. CONCLUSIONS AND
      CLINICAL RELEVANCE: Haemobartonella felis infections are more common in cats than
      previously recognized. Haemobartonella felis-OH is apparently more pathogenic
      than H. felis-CA. The PCR assay is more accurate than cytologic examination for
      detection of H. felis infection and is an effective clinical tool for the
      detection and differentiation of both H. felis strains known to infect cats.

PMID- 11327471
TI  - Induction of specific cytotoxic T-cell activity against xenogeneic target cells
      in carp (Cyprinus carpio).
AB  - OBJECTIVE: To investigate the induction of cytotoxic T cells in carp (Cyprinus
      carpio) after inoculation of fish with 2 xenogeneic line cells and to examine
      specificity of the cytotoxic activity. ANIMALS: 22 carp. PROCEDURE: Fish were
      inoculated with mouse myeloma line cells P3.NS-1/1Ag4.1 (NS-1) or chicken Marek's
      disease tumor-derived lymphoma line cells (MDCC MSB-1). Cytotoxic activity of
      immune lymphocytes was evaluated by incubating effector cells with homologous and
      heterologous target cells. Populations of effector cells were identified by
      blocking T-lymphocytes from effector cells, using anti-carp T-cell monoclonal
      antibody and complement. RESULTS: Lymphocytes in blood, spleen, and head kidney
      of carp inoculated with NS-1 cells or MDCC MSB-1 cells had dose-dependent
      cytotoxic effects against homologous target cells but not against heterologous
      target cells. Lymphocytes from noninoculated carp did not have cytotoxic effects.
      Depletion of T-lymphocytes in spleen cells from NS-1-inoculated carp resulted in
      a decrease of cytotoxic activity against NS-1 cells. Cytotoxic activity of spleen
      lymphocytes from NS-1-inoculated or noninoculated carp was not evident when
      cytotoxic tests were performed after addition of anti-NS-1 carp serum.
      CONCLUSIONS AND CLINICAL RELEVANCE: Inoculation with xenogeneic target cells
      induces a specific cytotoxic T-cell response in carp. Thus, cell-mediated
      immunity plays a role in defense against infection of parasitic organisms such as
      protozoa and helminths.

PMID- 11327473
TI  - Comparison of fermentation of selected fructooligosaccharides and other fiber
      substrates by canine colonic microflora.
AB  - OBJECTIVE: To compare fermentation characteristics of fructooligosaccharides
      (FOS) and other fiber substrates that are commonly found in canine diets. SAMPLE
      POPULATION: Fecal samples from 3 adult dogs. PROCEDURE: The ability of fiber
      substrates to be used in microbial fermentation reactions was assessed by use of
      an in vitro fermentation system. Dogs were fed a commercially available food, and
      feces were collected for use as the microbial inoculum. Substrates used were beet
      pulp, cellulose, soy fiber, mannanoligosaccharides (MOS), FOS, and 4 inulin
      products (inulin 1, 2, 3, and 4). Each substrate was incubated anaerobically with
      fecal inoculum and growth media for 6, 12, and 24 hours, and production of short
      chain fatty acids (SCFA) was measured. RESULTS: Total production of SCFA was
      higher for fermentation of the 4 inulin products and FOS, whereas fermentation of
      beet pulp, MOS, and soy fiber resulted in moderate concentrations of SCFA.
      Fermentation of cellulose produced the lowest concentrations of total SCFA
      without detection of butyrate or lactate. Butyrate production was greatest for
      fermentation of the 4 inulin products and FOS. Total lactate production was
      greatest for FOS and inulin 4. As expected, production of SCFA increased for all
      substrates as fermentation time increased. CONCLUSIONS AND CLINICAL RELEVANCE:
      Canine fecal microflora ferment FOS-containing substrates in a similar manner,
      with little fermentation of cellulose-based carbohydrates. Furthermore, results
      of an in vitro fermentation system indicate that fiber type affects the metabolic
      activity of microorganisms, thus influencing the amount and nature of the end
      products of fermentation.

PMID- 11327474
TI  - Sedative, analgesic, and cardiovascular effects of levomedetomidine alone and in
      combination with dexmedetomidine in dogs.
AB  - OBJECTIVE: To determine whether a high dose of levomedetomidine had any
      pharmacologic activity or would antagonize the sedative and analgesic effects of
      dexmedetomidine in dogs. ANIMALS: 6 healthy Beagles. PROCEDURE: Each dog received
      the following treatments on separate days: a low dose of levomedetomidine (10
      microg/kg), IV, as a bolus, followed by continuous infusion at a dose of 25
      microg/kg/h; a high dose of levomedetomidine (80 microg/kg), IV, as a bolus,
      followed by continuous infusion at a dose of 200 microg/kg/h; and a dose of
      isotonic saline (0.9% NaCl) solution, IV, as a bolus, followed by continuous
      infusion (control). For all 3 treatments, the infusion was continued for 120
      minutes. After 60 minutes, a single dose of dexmedetomidine (10 microg/kg) was
      administered IV. Sedation and analgesia were scored subjectively, and heart rate,
      blood pressure, respiratory rate, arterial blood gas partial pressures, and
      rectal temperatures were monitored. RESULTS: Administration of levomedetomidine
      did not cause any behavioral changes. However, administration of the higher dose
      of levomedetomidine enhanced the bradycardia and reduced the sedative and
      analgesic effects associated with administration of dexmedetomidine. CONCLUSIONS
      AND CLINICAL RELEVANCE: Results suggest that administration of dexmedetomidine
      alone may have some cardiovascular benefits over administration of medetomidine,
      which contains both dexmedetomidine and levomedetomidine. Further studies are
      needed to confirm the clinical importance of the effects of levomedetomidine in
      dogs.

PMID- 11327475
TI  - Impact of doramectin treatment at the time of feedlot entry on the productivity
      of yearling steers with natural nematode infections.
AB  - OBJECTIVE: To measure the reduction in fecal nematode egg counts and productivity
      impact of treatment of yearling steers with doramectin at entry into the feedlot,
      compared with control steers treated only with fenthion. ANIMALS: 6,096 crossbred
      yearling steers with a mean (+/- SD) body weight of 377.0 (+/- 37) kg. PROCEDURE:
      Steers were implanted with zeranol and alternately separated to fill each of 24
      pens. Groups of steers within 12 matched pairs of pens were randomly allocated to
      treatment with doramectin or no treatment with doramectin for internal nematodes.
      Fecal samples were collected from approximately every twentieth steer from each
      pen at day 0 and at reimplant (approx day 60). Each steer was weighed on day 0
      and at reimplant and then mean body weights of steers per pen were determined at
      120 to 140 days after trial initiation. RESULTS: Treatment steers had a
      significantly lower fecal egg count at reimplant than control steers. Treatment
      steers had a significantly greater mean daily gain during the study,
      significantly greater feed consumption, significantly lower feed-to-gain ratio,
      and significantly better quality carcass grades at slaughter. CONCLUSIONS AND
      CLINICAL RELEVANCE: Under the conditions of our trial, there was a significant
      fecal egg count reduction response to doramectin treatment, which resulted in
      significantly improved productivity. Results of economic analysis of return on
      investment indicated that even with low egg counts in heavy body weight cattle,
      nematode egg count reduction with doramectin significantly improved returns.

PMID- 11327476
TI  - Optimization of coagulometric tests that incorporate human plasma for
      determination of coagulation factor activities in canine plasma.
AB  - OBJECTIVE: To optimize methods used to measure coagulation factor activities in
      canine plasma, define reference ranges in dogs, and compare activities between
      canine and human plasma. SAMPLE POPULATION: Human plasma samples (n = 5) and
      plasma from healthy dogs (140) and dogs with low factor V activity (7), high
      factor V activity (7), and low factor VIII:C activity (6). PROCEDURE:
      Coagulometric tests incorporated human plasma deficient in a single coagulation
      factor (human deficient plasma). Standard curves were generated with pooled
      plasma from 100 healthy dogs. Effect of sample dilution was evaluated, using
      plasma from dogs with high or low factor V activity and low factor VIII:C
      activity. Reference ranges for healthy dogs were established. Activities in human
      plasma were determined by comparison with standard curves obtained with canine
      plasma. RESULTS: Activities of factors V and VIII:C in samples diluted < or =
      1:20 influenced results of tests for other coagulation factors. Activities of
      factors V and VIII:C in human plasma were significantly less than in canine
      plasma. For the other coagulation factors, significant differences in human
      plasma-to-canine plasma activity ratios were detected among different sample
      dilutions. CONCLUSIONS AND CLINICAL RELEVANCE: Accurate measurement of
      coagulation factor activities in canine plasma, using human deficient plasma,
      requires higher sample dilutions (ie, > 1:20) than typically used for human
      plasma. Differences in activities between human and canine plasma and
      nonparallelism of the standard curves emphasize the necessity for use of species
      specific standard curves for accurate determination of coagulation factor
      activity.

PMID- 11327477
TI  - Determination of reference values for glucose tolerance, insulin tolerance, and
      insulin sensitivity tests in clinically normal cats.
AB  - OBJECTIVE: To determine reference values and test variability for glucose
      tolerance tests (GTT), insulin tolerance tests (ITT), and insulin sensitivity
      tests (IST) in cats. ANIMALS: 32 clinically normal cats. PROCEDURE: GTT, ITT, and
      IST were performed on consecutive days. Tolerance intervals (ie, reference
      values) were calculated as means +/- 2.397 SD for plasma glucose and insulin
      concentrations, half-life of glucose (T1/2 glucose), rate constants for glucose
      disappearance (Kglucose and Kitt), and insulin sensitivity index (Si). Tests were
      repeated after 6 weeks in 8 cats to determine test variability. RESULTS:
      Reference values for T1/2glucose, Kglucose, and fasting plasma glucose and
      insulin concentrations during GTT were 45 to 74 minutes, 0.93 to 1.54 %/min, 37
      to 104 mg/dl, and 2.8 to 20.6 microU/ml, respectively. Mean values did not differ
      between the 2 tests. Coefficients of variation for T1/2glucose, Kglucose, and
      fasting plasma glucose and insulin concentrations were 20, 20, 11, and 23%,
      respectively. Reference values for Kitt were 1.14 to 7.3%/min, and for SI were
      0.57 to 10.99 x 10(4) min/microU/ml. Mean values did not differ between the 2
      tests performed 6 weeks apart. Coefficients of variation for Kitt and SI were 60
      and 47%, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: GTT, ITT, and IST can
      be performed in cats, using standard protocols. Knowledge of reference values and
      test variability will enable researchers to better interpret test results for
      assessment of glucose tolerance, pancreatic beta-cell function, and insulin
      sensitivity in cats.

PMID- 11327478
TI  - Fecal shedding of Giardia duodenalis, Cryptosporidium parvum, Salmonella
      organisms, and Escherichia coli O157:H7 from llamas in California.
AB  - OBJECTIVE: To evaluate fecal shedding of Giardia duodenalis, Cryptosporidium
      parvum, Salmonella organisms, and Escherichia coli O157:H7 from llamas in
      California with respect to host factors and management practices. ANIMALS: 354
      llamas from 33 facilities. PROCEDURE: Fecal specimens were collected and examined
      for G. duodenalis and C. parvum by means of immunofluorescent microscopy.
      Salmonella organisms were cultured by placing feces into selenite enrichment
      broth followed by selective media. Escherichia coli O157:H7 was cultured by use
      of modified tryptocase soy broth followed by sorbitol MacConkey agar, with
      suspect colonies confirmed by means of immunofluorescent microscopy. RESULTS: 12
      of 354 fecal specimens (3.4%) had G. duodenalis cysts. Younger llamas (crias)
      were more likely to be shedding cysts, compared with older llamas. Farm-level
      factors that increased the risk of shedding were large numbers of yearlings on
      the property (> 10), smaller pen sizes, large numbers of crias born during the
      previous year (> 10), and large pen or pasture populations (> 20). None of the
      354 fecal specimens had C. parvum oocysts. Seventy-six (from 7 facilities) and
      192 (from 22 facilities) llamas were tested for Salmonella organisms and E. coli
      O157:H7, respectively. All fecal specimens had negative results for these
      bacteria. CONCLUSIONS AND CLINICAL RELEVANCE: Shedding of G. duodenalis was
      primarily limited to crias 1 to 4 months old. Llamas from properties with large
      numbers of crias born in the previous year, resulting in large numbers of
      yearlings in the current year, were at greater risk of infection. In addition,
      housing llamas in smaller pens or pastures and managing llamas and crias in large
      groups also increased the risk of G. duodenalis shedding.

PMID- 11327479
TI  - Do we need a surgeon general's report on home and community based services? A
      personal and policy journey.

PMID- 11327480
TI  - Hospitalization patterns and palliation in the last year of life among residents
      in long-term care.
AB  - PURPOSE: This study compared patterns of care, including hospitalization, during
      the last year of life for a group of residents in institutional long-term care.
      These subjects were either implicitly or explicitly in palliative care modes
      versus those who remained in active treatment or blended care. DESIGN AND
      METHODS: The study used a retrospective chart review and both quantitative and
      qualitative methods of data collection and analysis to examine indepth the end-of
      life experiences of 41 nursing home residents who died in the nursing care unit
      of one large continuing care retirement community during an 18-month period.
      RESULTS: Most residents die in palliative care modes, but their movement into
      palliation with comfort care and symptom management is often slowed by indecision
      or inaction on the part of key decision makers, interrupted by aggressive acute
      care, or delayed until the last few days of life. IMPLICATIONS: Transitions from
      active curative care to palliative care are important for residents in permanent
      long-term care placements. Improved end-of-life care requires more attention to
      these transitions and to the decisions that residents, their families, and care
      teams are called upon to make.

PMID- 11327481
TI  - Innovation in nursing homes: which facilities are the early adopters?
AB  - PURPOSE: This study examined organizational and market factors associated with
      nursing homes that are most likely to be early adopters of innovations. Early
      adopter institutions, defined as the first 20% of facilities to adopt an
      innovation, are important because they subsequently facilitate the diffusion of
      innovations to others in the industry. DESIGN AND METHODS: Two groups of
      innovations were examined, special care units and subacute care services. I used
      discrete-time logistic regression analysis and nationally representative data
      from 13,162 facilities at risk of being early adopters of innovations during
      twelve 6-month intervals from 1992 to 1997. RESULTS: Organizational factors that
      increase the likelihood of early innovation adoption are larger bed size, chain
      membership, and high levels of private-pay residents. Four market factors that
      increase the likelihood of early innovation adoption are: a retrospective
      Medicaid reimbursement methodology, a more competitive environment, higher
      average income in the county, and a higher number of hospital beds in the county.
      IMPLICATIONS: This analysis shows that organizational and market characteristics
      of nursing homes affect their propensity toward early adoption of innovations.
      Some of the results may be useful for nursing home administrators and policy
      makers attempting to promote innovation.

PMID- 11327482
TI  - Pain in U.S. nursing homes: validating a pain scale for the minimum data set.
AB  - PURPOSE: The aim of this study was to validate a pain scale for the Minimum Data
      Set (MDS) assessment instrument and examine prevalence of pain in major nursing
      home subpopulations, including type of admission and cognitive status. DESIGN AND
      METHODS: This study considered validation of the MDS pain items and derivation of
      scale performed against the Visual Analogue Scale (VAS), using Automatic
      Interaction Detection. The derivation data describe 95 postacute care nursing
      home patients who are able to communicate. The scale is then used in
      retrospective analysis of 34,675 Michigan nursing home residents. RESULTS: A four
      group scale was highly predictive of VAS pain scores (variance explanation 56%)
      and therefore quite valid in detecting pain. In the prevalence sample, only 47%
      of postacute patients compared to 63% of postadmission patients reported no pain,
      and these percentages rose with increasing cognitive impairment. IMPLICATIONS:
      Pain is prevalent in nursing home residents, especially in those with cognitive
      dysfunction, and often untreated.

PMID- 11327483
TI  - Patterns of informal and formal caregiving among elders with private long-term
      care insurance.
AB  - PURPOSE: The purpose of this report is to provide basic descriptive information
      on community-dwelling, disabled, private long-term care (LTC) insurance
      policyholders who have accessed policy benefits. We focus on how benefits are
      used, whether claimants feel they are getting appropriate value from their
      policies, and what the patterns are of formal and informal service use. DESIGN
      AND METHODS: Data were obtained from a nationally representative sample of 693
      LTC insurance claimants who were receiving benefits while living in the community
      and 424 of their informal caregivers. Eight of the largest LTC insurance
      companies representing about 80% of the market participated in the study.
      RESULTS: LTC insurance benefits are well targeted; they serve those truly
      dependent on ongoing care. The vast majority of claimants are satisfied with
      their policies, understand their coverage, and find it easy to file claims.
      Because of their LTC benefits, substantial numbers of disabled elderly
      individuals report that they are able to remain at home instead of being forced
      to seek institutional care. The availability of LTC benefits reduces stress among
      informal caregivers. For most claimants, formal care did not replace informal
      caregiving. IMPLICATIONS: As the LTC insurance market continues to grow and
      mature, there will be changes in the profile of claimants, the service delivery
      system, and the design of policies. Expansions in the private market will be
      associated with a greater number of disabled elderly remaining in their homes
      with a maintenance of and enhanced resiliency of informal support networks.

PMID- 11327484
TI  - Early caregiving and adult depression: good news for young caregivers.
AB  - PURPOSE: Limited information is available on the effects of caregiving
      experiences on the adult development of caregivers under 21 years old in the
      United States. The current study provided an examination of the effects of
      youthful caregiving on the mental health of these persons when adults. DESIGN AND
      METHODS: Twelve individuals, 23 to 58 years old, were given brief phone
      interviews with semistructured questions, and then they completed questionnaires
      on their early caregiving experiences and current mental health. To be included,
      respondents must have provided primary caregiving assistance (i.e., bathing,
      dressing, feeding, etc.) for at least one parent when the caregiver was under 21
      years old. RESULTS: The findings showed that individuals were young caregivers
      for parents with a number of problems, ranging from dementia to drug abuse.
      Individuals reported more positive mental health than negative mental health, and
      only two individuals had scores indicative of clinical depressive symptoms.
      IMPLICATIONS: It appears that early caregiving experiences may not result in
      universally negative consequences in the adulthood of young caregivers.

PMID- 11327486
TI  - American grandparents providing extensive child care to their grandchildren:
      prevalence and profile.
AB  - PURPOSE: This study sought to determine the prevalence and profile of
      grandparents providing extensive care for a grandchild (grandparents who provide
      30+ hours per week or 90+ nights per year of child care, yet are not the primary
      caregiver of the grandchild). DESIGN AND METHODS: Secondary analysis of the 3,260
      grandparent respondents in the 1992-94 National Survey of Families and Households
      (NSFH). Extensively caregiving grandparents were compared with custodial
      grandparents (those with primary responsibility for raising a grandchild for 6+
      months), noncaregivers, occasional caregivers (<10 hours per week), and
      intermediate caregivers using chi-square tests, one-way analysis of variance
      tests, and logistic regression analyses. RESULTS: Close to 7% of all grandparents
      provided extensive caregiving, as did 14.9% of those who had provided any
      grandchild care in the last month. Extensive caregivers most closely resembled
      custodial caregivers and had least in common with those grandparents who never
      provided child care. IMPLICATIONS: Areas for future research, policy, and
      practice are highlighted, including the potential impact of welfare reform
      legislation on extensively caregiving grandparents.

PMID- 11327485
TI  - Retirement effects on parent-adult child contacts.
AB  - PURPOSE: This study examined whether parents' retirement influences their
      contacts (visits, telephone/letter) with adult children outside the household.
      DESIGN AND METHODS: The study relied on data from the National Survey of Families
      and Households. The sample consisted of parent-adult child dyads where parents
      were aged 55-75 at time 2 and adult children resided outside the household at
      both waves (N = 2,153 parent-adult child dyads, based on reports from 792
      parents). Generalized estimating equations (GEE) with robust standard errors were
      used. RESULTS: Retirement has no significant effect on telephone contacts.
      Retired parents maintain frequent visits with children. For children living
      within 10 miles, mothers' retirement is associated with fewer and fathers'
      retirement with more visits. This trend varies by number of children, length of
      retirement, and child's gender. For children living more than 10 miles away,
      retired mothers decrease visits with childless children, whereas retired fathers
      increase visits with childless children. IMPLICATIONS: We attribute these
      findings to the gender-specific salience of child contacts for retirees and
      suggest that future research address children's and parents' expectations for
      postretirement contacts.

PMID- 11327487
TI  - Toward the conceptualization and measurement of caregiver burden among Pueblo
      Indian family caregivers.
AB  - PURPOSE: The purpose of this study was to evaluate burden experienced by a group
      of American Indian primary family caregivers and to determine if caregiver burden
      is a multi-dimensional concept. DESIGN AND METHODS: This analysis is based on the
      results of a survey questionnaire administered to 169 Pueblo primary family
      caregivers in New Mexico. RESULTS: Analysis of the items composing the Caregiver
      Burden scale indicated that caregiver burden is multidimensional and consists of
      several types of burden. Caregiver burden, as identified in this sample, is
      composed of four dimensions: role conflict, negative feelings, lack of caregiver
      efficacy, and guilt. Investigations of caregiver burden should consider the
      multidimensionality of this experience and evaluate burden accordingly.
      IMPLICATIONS: By identifying the specific type of burden that a caregiver
      experiences, interventions can be targeted more accurately to support family
      caregiving.

PMID- 11327488
TI  - Retirement migration counties in the southeastern United States: geographic,
      demographic, and economic correlates.
AB  - This article is a brief empirical attempt to identify rural areas in the
      Southeast United States that have consistently attracted older migrants since
      1950 and to ascertain the social, demographic, and geographic characteristics of
      these areas of destination that differentiate them from otherwise (initially)
      similar areas. These counties are followed over the successive censuses from 1950
      through 1990, identifying those that have consistently experienced elderly in
      migration at a rate substantially greater than the overall level. These
      retirement counties are concentrated in Florida, on the fringes of or adjacent to
      metropolitan areas or in mountain and coastal locations. The article presents
      regression analysis of geographic, demographic, and economic/structural
      correlates of migration. This analysis suggests that retirees are attracted to
      coastal locations whose existing populations have consistently achieved some
      measure of prosperity and are not dissimilar from the retirees themselves.

PMID- 11327489
TI  - Living arrangements among older immigrants in the United States.
AB  - This analysis uses data from the 1990 5% Public Use Microdata Sample (PUMS) to
      identify the individual-level characteristics that influence residential
      dependence among immigrants age 60 and older in the United States. Particular
      attention is given to differences among 11 immigrant groups. Separate models are
      shown by gender and marital status. The results indicate that Hispanic and most
      Asian immigrants, particularly those from Mexico, Central or South America,
      India, and the Pacific Islands, are at a greater risk of living with family than
      non-Hispanic White immigrants. Although resource, need, and demographic
      characteristics influence the risk of living with Family, these individual-level
      characteristics do not explain the observed differences across the immigrant
      groups. These findings suggest that preferences that are shaped by the
      immigrant's experience as well as cultural background are an important
      determinant of immigrant living arrangements in later life.

PMID- 11327491
TI  - The effects of membership in church-related associations and labor unions on age
      differences in voluntary association affiliations.
AB  - PURPOSE: When compositional differences between age groups are controlled, the
      bivariate, curvilinear pattern of age differences in voluntary association
      memberships is replaced by one in which peak membership levels occur in late
      middle age and remain relatively stable thereafter. We sought to determine if
      this adjusted pattern persists when widespread memberships in two types of
      associations are removed: (1) church-related organizations, in which membership
      increases with age but may be confounded with church membership per se; and (2)
      labor unions, in which membership is also widespread but may not be "voluntary."
      DESIGN AND METHODS: Total memberships in 14 types of associations were examined
      using aggregated data from 12 national surveys conducted between 1974 and 1994.
      RESULTS: The familiar curvilinear relationship at the bivariate level appears,
      but in the multivariate analysis, membership levels rise from ages 18-24 through
      55-59 and persist close to that level through ages 85 and older. IMPLICATIONS:
      The results reaffirm that age differences in voluntary association affiliations
      are due to age-based compositional differences; they also show, however, that the
      pattern observed with controls is neither driven by membership in church-related
      "associations" nor altered when membership in labor unions is excluded.

PMID- 11327490
TI  - The Spiritual History Scale in four dimensions (SHS-4): validity and reliability.
AB  - The goals of this study were to develop a valid, reliable measure of lifetime
      religious and spiritual experience and to assess its value in explaining late
      life health. Procedures included semi-structured interviews with Duke Aging
      Center volunteers (n = 30), followed by structured interviews of a stratified,
      random sample of subjects (n = 157) from the Established Populations for
      Epidemiologic Studies of the Elderly at Duke University. Principal components
      analysis suggested four factors with favorable psychometrics. Health-impaired
      subjects reported a history of seeking/receiving divine aid (God Helped). At
      every level of impairment, Lifetime Religious Social Support and current
      religious attendance were positively correlated. Regardless of current
      attendance, subjects who reported higher Lifetime Religious Social Support
      received more instrumental social support. Healthy behaviors were associated with
      both God Helped and Lifetime Religious Social Support. Cost of Religiousness
      predicted depressive symptoms and impaired social support. Family History of
      Religiousness was unrelated to late-life health. Evaluation of the Spiritual
      History Scale in Four Dimensions (SHS-4) across geographical settings, cultural
      subgroups, age cohorts, and clinical samples is warranted.

PMID- 11327492
TI  - The design and implementation of a restorative care model for home care.
AB  - PURPOSE: The increasing demand for geriatric home-based care makes it timely to
      examine how the existing system can become most effective and efficient in
      promoting the functional outcomes of older patients. DESIGN AND METHODS: A
      multidisciplinary work group identified home care agency policies, misconceptions
      of older adults and their caregivers, and practice patterns of nurses,
      therapists, and home health aides that can impede patients' progress toward
      functional independence. This article describes the process that one home care
      agency used to remove these obstacles. RESULTS AND IMPLICATIONS: The work group
      developed and implemented a restorative model of care that integrates the medical
      treatments for acute disease processes and the personal care and rehabilitative
      interventions directed toward chronic disabilities, to improve the functional
      outcomes of older adults receiving home care.

PMID- 11327493
TI  - National standards for the long-term care ombudsman program and a tool to assess
      compliance: the Huber Badrak Borders Scales.
AB  - PURPOSE: We propose national standards previously recommended for the Long-Term
      Care Ombudsman Program by an Institute of Medicine program evaluation committee,
      and introduce a tool to measure the compliance of local ombudsman programs to
      those standards: the Huber Badrak Borders Scales. METHODS: The best practices for
      ombudsman programs detailed in the committee's report were adapted to 43 Likert
      type scales that were then averaged into 10 infrastructure component scales: (a)
      program structure, (b) qualifications of local ombudsmen, (c) legal authority,
      (d) financial resources, (e) management information systems, (f) legal resources,
      (g) human resources, (h) resident advocacy services, (i) systemic advocacy, and
      (j) educational services. The scales were pilot-tested in 1996 and 1999 with
      Kentucky ombudsmen. RESULTS: The means of 9 of these 10 scales were higher in
      1999 than in 1996, suggesting that local ombudsman programs were more in
      compliance with the proposed standards in 1999 than three years earlier.
      IMPLICATIONS: The development process consisted of 10 adopt-test-revise-retest
      steps that can be replicated by other types of programs to develop program
      compliance tools.

PMID- 11327494
TI  - Ageism is a major problem in our society.

PMID- 11327495
TI  - Extraction of the aortic and pulmonary components of the second heart sound using
      a nonlinear transient chirp signal model.
AB  - The objective of this paper is to adapt and validate a nonlinear transient chirp
      signal modeling approach for the analysis and synthesis of overlapping aortic
      (A2) and pulmonary (P2) components of the second heart sound (S2). The approach
      is based on the time-frequency representation of multicomponent signals for
      estimating and reconstructing the instantaneous phase and amplitude functions of
      each component. To evaluate the accuracy of the approach, a simulated S2 with A2
      and P2 components having different overlapping intervals (5-30 ms) was
      synthesized. The simulation results show that the technique is very effective for
      extracting the two components, even in the presence of noise (-15 dB). The
      normalized root-mean-squared error between the original A2 and P2 components and
      their reconstructed versions varied between 1% and 6%, proportionally to the
      duration of the overlapping interval, and it increased by less than 2% in the
      presence of noise. The validated technique was then applied to S2 components
      recorded in pigs under normal or high pulmonary artery pressures. The results
      show that this approach can successfully isolate and extract overlapping A2 and
      P2 components from successive S2 recordings obtained from different heartbeats of
      the same animal as well from different animals.

PMID- 11327496
TI  - Multiple-window spectrogram of peaks due to transients in the
      electroencephalogram.
AB  - In this paper, peak matched multiple windows (PM MW) were used to estimate the
      spectrogram of the electroencephalogram (EEG). We focussed on the ability to
      estimate frequency changes, and especially resolving close peaks. A peak of known
      frequency was evoked in the EEG in a predetermined time interval. The PM MW
      spectrogram was compared to the commonly used single Hanning window and to
      weighted overlapped segment averaging in simulations and for real-data. The PM MW
      were shown to give estimates with good resolution and low variance.

PMID- 11327497
TI  - Deconvolution and wavelet-based methods for membrane current estimation from
      simulated fractionated electrograms.
AB  - In infarcted myocardium, extracellular recordings exhibit multiple deflections
      due to irregular pathway of the electric impulse. In this work the problem of
      distinguishing local from distant deflections is tackled. In order to evaluate
      the proposed methods in a controlled setting, simulated data are used, following
      both Beeler-Reuter and Luo-Rudy kinetics. The input is an array of electrograms
      positioned on grid-points of a rectangular grid and the output is an array of
      estimates of the membrane current. First, deconvolution techniques are used in
      the form of spatial filtering for membrane current estimation from the
      extracellular recordings. Second, the extracellular recordings undergo wavelet
      based transformation, followed by a spatial filter which enhances local activity
      deflections and suppresses distant activity deflections. It is shown that wavelet
      filtering of the extracellular recordings acts as an evaluator of the efficiency
      of the deconvolution techniques for the membrane current estimation.
      Subsequently, activation times based on the results from the two methods are used
      for the reconstruction of the propagation pattern in a zig-zag case in two
      dimensional grids. It is shown that the wavelet-based method is more robust, and
      can work well even in cases where the grid interval in the y direction is four
      times larger than the single cell size.

PMID- 11327498
TI  - A wavelet-based continuous classification scheme for multifunction myoelectric
      control.
AB  - This work represents an ongoing investigation of dexterous and natural control of
      powered upper limbs using the myoelectric signal. When approached as a pattern
      recognition problem, the success of a myoelectric control scheme depends largely
      on the classification accuracy. A novel approach is described that demonstrates
      greater accuracy than in previous work. Fundamental to the success of this method
      is the use of a wavelet-based feature set, reduced in dimension by principal
      components analysis. Further, it is shown that four channels of myoelectric data
      greatly improve the classification accuracy, as compared to one or two channels.
      It is demonstrated that exceptionally accurate performance is possible using the
      steady-state myoelectric signal. Exploiting these successes, a robust online
      classifier is constructed, which produces class decisions on a continuous stream
      of data. Although in its preliminary stages of development, this scheme promises
      a more natural and efficient means of myoelectric control than one based on
      discrete, transient bursts of activity.

PMID- 11327499
TI  - Derived fuzzy knowledge model for estimating the depth of anesthesia.
AB  - Reliable and noninvasive monitoring of the depth of anesthesia (DOA) is highly
      desirable. Based on adaptive network-based fuzzy inference system (ANFIS)
      modeling, a derived fuzzy knowledge model is proposed for quantitatively
      estimating the DOA and validate it by 30 experiments using 15 dogs undergoing
      anesthesia with three different anesthetic regimens (propofol, isoflurane, and
      halothane). By eliciting fuzzy if-then rules, the model provides a way to address
      the DOA estimation problem by using electroencephalogram-derived parameters. The
      parameters include two new measures (complexity and regularity) extracted by
      nonlinear quantitative analyses, as well as spectral entropy. The model
      demonstrates good performance in discriminating awake and asleep states for three
      common anesthetic regimens (accuracy 90.3 % for propofol, 92.7 % for isoflurane,
      and 89.1% for halothane), real-time feasibility, and generalization ability
      (accuracy 85.9% across the three regimens). The proposed fuzzy knowledge model is
      a promising candidate as an effective tool for continuous assessment of the DOA.

PMID- 11327500
TI  - Estimation of radiative heat transfer using a geometric human model.
AB  - In order to provide a detailed estimate of radiative heat transfer between a
      human body and its surrounding environment, we have developed a geometric model
      of a human form and an algorithm. The model closely resembles the actual shape of
      a human body and is composed of small quadrilateral surfaces. Dealing with an
      object or a space with an arbitrary shape, the developed algorithm can judge
      efficiently whether there is an obstruction between a pair of surfaces. As a
      result, the angle factors between a pair of surfaces that only occur during
      radiative heat transfer can be defined. The distribution of the radiative heat
      transfer rates shows the characteristics of body shape and variations in posture.

PMID- 11327501
TI  - A computational neural approach to support the discovery of gene function and
      classes of cancer.
AB  - Advances in molecular classification of tumours may play a central role in cancer
      treatment. Here, a novel approach to genome expression pattern interpretation is
      described and applied to the recognition of B-cell malignancies as a test set.
      Using cDNA microarrays data generated by a previous study, a neural network model
      known as simplified fuzzy ARTMAP is able to identify normal and diffuse large B
      cell lymphoma (DLBCL) patients. Furthermore, it discovers the distinction between
      patients with molecularly distinct forms of DLBCL without previous knowledge of
      those subtypes.

PMID- 11327502
TI  - Characteristics of silicon nitride after O2 plasma surface treatment for pH-ISFET
      applications.
AB  - Silicon nitride (Si3N4) sensing gate pH-ion-selective field effect transistors
      (ISFETs) were treated by 2.54-GHz microwave O2 plasma, the results show the ISFET
      sensitivity has an advantage up to 24% increment after the plasma treatment.
      Electron spectroscopy for chemical analysis (ESCA) is used to make sure that the
      plasma treatment is not just a native oxide cleaning procedure. The samples,
      which were immobilized with glutaraldehyde used as a bifunctional reagent and 3
      aminopropyItriethoxysilane used as an adhesion promoter were studied. The binding
      force between the glucose oxidase and glutaraldehyde immobilized samples, and the
      element concentrations of nitrogen in 3-aminopropyltriethoxysilane immobilized
      samples are higher which were treated by plasma.

PMID- 11327503
TI  - A simultaneous multichannel monophasic action potential electrode array for in
      vivo epicardial repolarization mapping.
AB  - While the recording of extracellular monophasic action potentials (MAPs) from
      single epicardial or endocardial sites has been performed for over a century, we
      are unaware of any previous successful attempt to record MAPs simultaneously from
      a large number of sites in vivo. We report here the design and validation of an
      array of MAP electrodes which records both depolarization and repolarization
      simultaneously at up to 16 epicardial sites in a square array on the heart in
      vivo. The array consists of 16 sintered Ag-AgCl electrodes mounted in a common
      housing with individual suspensions allowing each electrode to exert a controlled
      pressure on the epicardial surface. The electrodes are arranged in a square
      array, with each quadrant of four having an additional recessed sintered Ag-AgCl
      reference electrode at its center. A saline-soaked sponge establishes ionic
      contact between the reference electrodes and the tissue. The array was tested on
      six anesthetized open-chested pigs. Simultaneous diagnostic-quality MAP
      recordings were obtained from up to 13 out of 16 ventricular sites. Ventricular
      MAPs had amplitudes of 10-40 mV with uniform morphologies and stable baselines
      for up to 30 min. MAP duration at 90% repolarization was measured and shown to
      vary as expected with cycle length during sustained pacing. The relationship
      between MAP duration and effective refractory period was also confirmed. The
      ability of the array to detect local differences in repolarization was tested in
      two ways. Placement of the array straddling the atrioventricular (AV) junction
      yielded simultaneous atrial or ventricular recordings at corresponding sites
      during 1:1 and 2:1 AV conduction. Localized ischemia via constriction of a
      coronary artery branch resulted in shortening of the repolarization phase at the
      ischemic, but not the nonischemic, sites. In conclusion, these results indicate
      that the simultaneous multichannel MAP electrode array is a viable method for in
      vivo epicardial repolarization mapping. The array has the potential to be
      expanded to increase the number of sites and spatial resolution.

PMID- 11327504
TI  - Development of a magnetic sensing device for tooth displacement under orthodontic
      forces.
AB  - We have developed a system for measuring tooth displacement from orthodontic
      force. Eight small magnetic sensors and a magnet are combined to measure three
      dimensional displacement. Sensors, arranged cubically in the three planes of
      space, are placed in the mouth and fixed to the posterior teeth by a splint. A
      magnet is placed in the center of the eight sensors and attached to a front tooth
      that is subjected to orthodontic force. Sensors detect the magnet's movement as
      target tooth displacement. The system was designed to achieve displacement
      resolution of 1 microm. The mean percentage of measurement errors was determined
      to be less than 1% in a 600-cubic-microm volume from calibration. The system was
      tested clinically on human teeth. Although the oral environment, with high
      temperature and humidity, was not agreeable with the sensors, this system was
      stable and accurate enough for quantitative measurement of tooth displacement.
      The advantage of this system is the ability to detect tooth trajectories by
      decomposing displacement into translation and rotation and to determine the
      position of the center of rotation from these parameters.

PMID- 11327505
TI  - Flexible polyimide-based intracortical electrode arrays with bioactive
      capability.
AB  - The promise of advanced neuroprosthetic systems to significantly improve the
      quality of life for a segment of the deaf, blind, or paralyzed population hinges
      on the development of an efficacious, and safe, multichannel neural interface for
      the central nervous system. The candidate implantable device that is to provide
      such an interface must exceed a host of exacting design parameters. We present a
      thin-film, polyimide-based, multichannel intracortical Bio-MEMS interface
      manufactured with standard planar photo-lithographic CMOS-compatible techniques
      on 4-in silicon wafers. The use of polyimide provides a mechanically flexible
      substrate which can be manipulated into unique three-dimensional designs.
      Polyimide also provides an ideal surface for the selective attachment of various
      important bioactive species onto the device in order to encourage favorable long
      term reactions at the tissue-electrode interface. Structures have an integrated
      polyimide cable providing efficient contact points for a high-density connector.
      This report details in vivo and in vitro device characterization of the
      biological, electrical and mechanical properties of these arrays. Results suggest
      that these arrays could be a candidate device for long-term neural implants.

PMID- 11327506
TI  - A new algorithm for autoreconstruction of catheters in computed tomography-based
      brachytherapy treatment planning.
AB  - This paper describes innovative software for automatic reconstruction, which we
      term autoreconstruction, of plastic and metallic brachytherapy catheters using
      computed tomography (CT) data. No such automatic facility has previously existed
      in any treatment planning software. The patient data consists of a set of post
      implantation CT images with the catheters in situ in their final positions. This
      new software solves those difficulties which arise when the catheters are
      intersecting or when loop techniques are used. With the software algorithms,
      catheter reconstruction time is significantly reduced and accuracy is also
      improved when compared with that achieved using the classical manual method of CT
      slice-by-CT-slice reconstruction.

PMID- 11327508
TI  - An efficient method for quantifying the multichannel EEG spatial-temporal
      complexity.
AB  - The complexity index (delta) quantifies the intrinsic dimensionality of the
      global complexity of a point set, and was shown to be able to characterize
      electroencephalogram spatial-temporal features. The complexity index is
      conceptually comprehensible and easily implemented, yet, it is time consuming. In
      this paper, we present an efficient computational method based on the projection
      of the high-dimensional state-space points onto a one-dimensional axis. The
      computational time decreases by at least 50%, without affecting the measure
      accuracy.

PMID- 11327507
TI  - A surface-marker imaging system to measure a moving knee's rotational axis
      pathway in the sagittal plane.
AB  - This paper describes a new surface-marker imaging system designed to measure the
      rotational axis pathway (RAP) of a moving knee in the sagittal plane. Measurement
      of this parameter can provide important information about a knee's slipping and
      rolling action that can aid clinical assessment. Seated subjects are video
      recorded as they actively extend their legs. A series of stills is then captured
      and analyzed to extract the coordinates of markers placed on the subjects upper
      and lower legs. These coordinates are then processed to deduce an instant center
      of rotation (ICR) for each still. These ICRs are then plotted to derive the
      joint's RAP. The system has been validated with a mechanical model and tested in
      a clinical study of ten patients with unilateral anterior cruciate ligament (ACL)
      ruptures. The study found that the system could consistently measure differences
      between a patients normal and injured knees. Leg extension caused the normal
      knees ICRs to displace anteriorly with a mean value of 17.4 mm, whereas the
      injured knees had a mean displacement of 7.5 mm. This loss of roll in the ACL
      deficient knees is consistent with their abnormal biomechanical arrangement.

PMID- 11327509
TI  - A self-oscillating detuning-insensitive class-E transmitter for implantable
      microsystems.
AB  - This paper describes a low-cost, self-oscillating, detuning-in-sensitive, class-E
      driver for transcutaneous power and data transmission to implantable
      microsystems. A voltage feedback scheme using a fast comparator for zero-crossing
      detection and a CMOS start-up circuit were used to stabilize the class-E
      operation for various transmitter coil inductance values. This technique solves
      the common problem of mismatch between the switching frequency of the driving
      device and the resonant frequency of the load network, which can cause excessive
      power loss and damage to the active device. Data is transmitted by AM modulation
      of the carrier through switching the power supply between two levels. The
      transmitter uses a 9-V supply, consumes 212 mA, operates at 3.9 MHz, and has an
      efficiency of 71%. The efficiency is stable (< 2% change) against 13% variations
      in the inductance value of a pancake shaped transmitter coil. Index Terms
      Biomedical microsystems, class-E transmitter, implantable electronics, inductive
      powering, transcutaneous links.

PMID- 11327510
TI  - Differential toxicity expression of gentamicine in five-sixths nephrectomized
      rats assigned to three progressive stages of renal dysfunction--establishment of
      a new screening approach.
AB  - Progressive renal dysfunction in 5/6 nephrectomized (NX) rats can be
      physiologically divided into three stages, coinciding with morphological stages,
      after definition of physiological parameters for identification of stage. Now,
      for the establishment of a toxicity screening approach using 5/6 NX rats, our
      concept, "Differential toxicity synchronized with renal dysfunction process could
      be identified using 5/6 NX rats" was examined by dosing gentamicin. Firstly,
      electrophoretic fractional changes of urinary proteins during gentamicin
      treatment were clarified with determination of amino acid sequences and the three
      differential features were proven, revealing the unpredictable depression of
      urinary albumin with progression of the stages in NX rats. Secondly, marked
      elevation of urinary lactate dehydrogenase (LDH) and glucose (GLU) was evident,
      indicating the intensified hypoxic conditions and glycolysis in tubular cells
      synchronized with increased tubular damage. Thirdly, these transit metabolic
      changes were proven as intensive cause for the advancement of renal dysfunction
      by the reduction of FRelectrolytes and water at the end of each dosing period.
      These results indicate that toxicity studies of newly developed drugs using 5/6
      NX rats have potentiality prior to clinical dosing to the patients.

PMID- 11327511
TI  - Compartmental model for aluminium biokinetics.
AB  - An open compartmental model for describing aluminium biokinetics is presented
      with a central compartment consisting of transferrin- and citrate-bound aluminium
      in blood plasma and interstitial fluid, and three peripheral compartments for
      organs, muscles and bones and the gastro-intestinal tract. The rate constants
      describing the transport of aluminium are normalized to an estimated plasma
      volume and do not depend on the size of the individual. Effects due to changes in
      compartmental sizes or to transport characteristics are described. The model is
      applied to biokinetics studies of a volunteer after i.v. administration and of
      Sprague-Dawley rats with different iron status and with nephrectomization after
      p.o. administration of 26Al.

PMID- 11327512
TI  - Fatal weeverfish sting.
AB  - We report a case of fatal weeverfish sting. An 18-year-old man was stung on the
      left leg by a weeverfish, which he was attempting to capture while snorkelling
      off the coast of Majorca (Spain). The man felt intense pain, but managed to swim
      to his boat where he lost consciousness after boarding rapidly. An hour later,
      when examined by a doctor, the subject was found to be in cardiorespiratory
      arrest. Reanimation manoeuvres were unsuccessful. The most import post-mortem
      findings were in the skin and lungs. A puncture wound, which traversed the
      greater saphenous vein and was covered by an intense haemorrhagic infiltrate, was
      observed in the skin. The lungs showed haemorrhagic alveolar oedema.

PMID- 11327513
TI  - The miseries of passive smoking.
AB  - Passive smoking is defined as an involuntary exposure to a combined but diluted
      cigarette sidestream smoke (SS, gas and particle phases that are evolved from the
      smoldering end of a cigarette while the smoker is not puffing) and the exhaled
      smoke from smokers. SS contains numerous cytotoxic substances such as polycyclic
      aromatic hydrocarbons (PAHs), aromatic amines, nitrosamines, heavy metals,
      poisonous gases, pesticide residues, and radioactive elements in quantities much
      higher than those found from the cigarette mainstream smoke (MS) which is puffed
      by smokers. Passive smoking is found to be the cause of death from cancers and
      cardiac disease. Furthermore, it damagingly involves reproductive organs, the
      nervous system, genetic materials, and is particularly hazardous to mother and
      child during pregnancy and to those with a history of asthma, chronic infections,
      induced or earned immune deficiency, or predisposed susceptibility.

PMID- 11327514
TI  - Trichothecene toxicity on human megakaryocyte progenitors (CFU-MK).
AB  - Trichothecenes are mycotoxins produced by various species of fungi, which can
      occur on various agricultural products. Among these compounds, T-2 toxin, HT-2
      toxin, diacetoxyscirpenol (DAS) and deoxynivalenol (DON) are the most naturally
      encountered and the most potent trichothecenes. Consumption of trichothecene
      contaminated foods by farm animals and humans leads to mycotoxicosis.
      Trichothecenes are known to induce haematological disorders such as neutropenia,
      aplastic anemia and thrombocytopenia in humans and animals. Four trichothecenes,
      T-2 toxin, HT-2 toxin, DAS and DON have been tested on human platelet progenitors
      (CFU-MK) using a culture model of CFU-MK optimized for toxicological studies.
      Trichothecenes cause, at low concentrations, cytotoxic effects in megakaryocyte
      progenitors, which could induce thrombocytopenia. Sensitivity of human CFU-MK is
      compared to respective sensitivities of human red blood cell progenitors (BFU-E)
      and white blood cell progenitors (CF-U-GM) that were described in previous works.

PMID- 11327515
TI  - The characterisation and uptake of paraquat in cultured baboon kidney proximal
      tubule cells (bPTC).
AB  - A primary culture of baboon proximal tubule cells (bPTC) was prepared and
      characterised using LLC-PK1 cells of proximal tubule origin and MDCK cells of
      distal tubule origin, as positive and negative references, respectively. The
      proximal tubular origin of the bPTC was determined by morphological studies,
      immunoperoxidase staining and the expression of proximal tubule markers alkaline
      phosphatase and gammaglutamyltransferase. The hypothesis that paraquat (PQ) is
      transported by the bPTC was investigated. The cytotoxic threshold for PQ in these
      cells was determined and compared to the LLC-PK1 and MDCK cells. Furthermore,
      this study investigated the transport of the monovalent cation tetraethyl
      ammonium (TEA) and the polyvalent cation cimetidine in the bPTC and demonstrated
      their effect on the cellular uptake of PQ. The cytotoxic threshold of PQ in the
      bPTC, determined by cellular viability studies using the method of Trypan blue
      exclusion, is 0.05 mM at 2 h incubation. The LC50 after 24 h is 76, 61 and 455
      microM for the bPTC, LLC-PK1 and MDCK cells, respectively. This indicates that
      proximal tubule cells are more susceptible to PQ toxicity compared to distal
      tubule cells, which is consistent with clinical PQ toxicity where renal damage is
      found predominantly in the proximal renal tubules. The cations PQ and cimetidine
      were actively transported by the bPTC. The uptake of PQ (0.05 mM) commenced after
      15 min whereas cimetidine (0.5 mM) uptake was evident after 2 min. Furthermore,
      cimetidine was shown to compete with PQ for uptake in the bPTC. Coincubating PQ
      (0.05 mM) and cimetidine (0.5 mM) for 60 min resulted in an approximate 50%
      decrease in PQ uptake. The cation TEA was not transported by the bPTC suggesting
      either a genetic mutation or complete absence of the transporter for TEA in the
      cells. The results suggest that PQ may be transported by the same cation
      transporter as cimetidine and not TEA, indicating PQ uptake in the bPTC to be via
      a polyvalent organic cation transporter.

PMID- 11327516
TI  - Homeopathy: a multifaceted scientific renaissance.

PMID- 11327517
TI  - Ernst fails to address key charges.

PMID- 11327518
TI  - Curanderismo: a picture of Mexican-American folk healing.

PMID- 11327519
TI  - An analysis of nine proprietary Chinese red yeast rice dietary supplements:
      implications of variability in chemical profile and contents.
AB  - OBJECTIVES: Some strains of Chinese red yeast rice, when prepared by solid
      fermentation, produce compounds called monacolins that inhibit cholesterol
      production. When used as a dietary supplement to achieve and maintain healthy
      cholesterol levels, Chinese red yeast rice has significant potential to reduce
      health care costs and contribute to public health by reducing heart disease risk
      in individuals with moderate elevations of circulating cholesterol levels.
      Whereas one proprietary strain of Chinese red yeast rice has been demonstrated to
      lower cholesterol levels significantly in clinical trials, other strains being
      sold as Chinese red yeast rice dietary supplements have not undergone similar
      evaluation. In order to determine whether the results of a clinical trial
      conducted with one strain of Chinese red yeast rice could be generalized to other
      preparations of Chinese red yeast rice, nine different commercially available
      dietary supplements were purchased tested for chemical constituents. DESIGN:
      Monacolins were measured by high performance liquid chromatography (HPLC) that
      separates the various monacolins in Chinese red yeast rice. Citrinin
      concentration, a toxic fermentation byproduct, was measured by radioimmunoassay.
      RESULTS: Total monacolin content varied from 0% to 0.58% w/w and only 1 of 9
      preparations had the full complement of 10 monacolin compounds. Citrinin was
      found at measurable concentrations in 7 of the 9 preparations. CONCLUSIONS: The
      findings from clinical trials demonstrating significant and clinically relevant
      cholesterol reduction using a defined Chinese red yeast rice preparation
      containing 10 different monacolins cannot be generalized to preparations that do
      not contain the same levels and profile of monacolins. Standardized manufacturing
      practices should be established for Chinese red yeast rice sold as a dietary
      supplement in order ensure equivalence of content of active ingredients in
      preparations being sold to the public and to limit the production of unwanted
      byproducts of fermentation such as citrinin. In common with other botanical
      dietary supplements, the full potential of this product will not be realized
      until standards for production and labeling of Chinese red yeast rice are further
      developed.

PMID- 11327520
TI  - Can homeopathically prepared mercury cause symptoms in healthy volunteers? A
      randomized, double-blind placebo-controlled trial.
AB  - OBJECTIVE: To pilot a method for determining whether homeopathically prepared
      mercury causes more symptoms (a "drug proving") in healthy volunteers than
      placebo. METHODS: One hundred and eighteen (118) healthy volunteers ages 18 to 65
      were recruited by local advertising. Subjects unfamiliar with homeopathy
      undertook a 1-week single-blind placebo run-in, a 1-week of double-blind,
      randomized treatment on either homeopathically prepared mercury 12C or placebo,
      and a third week of placebo run-out. Each day, symptoms were recorded on a
      checklist that included both true mercury symptoms and symptoms not expected to
      be caused by mercury (false symptoms). Additional symptoms were assessed by open
      reporting. Outcome was assessed by calculating a score for each day as the number
      of true symptoms minus the number of false symptoms. The mean score during
      placebo was then subtracted from the mean score for weeks two and three of the
      trial. RESULTS: Fourteen (14) subjects dropped out during placebo run-in. The
      remaining 104 completed the trial. Baseline comparability was good. Mean
      difference score was -0.125 (SD 3.47) for mercury and -0.221 (SD 3.01) for
      placebo (p > 0.2). No significant differences between groups were found for the
      number of subjects meeting predefined criteria for a drug-proving reaction.
      CONCLUSION: This pilot study failed to find evidence that mercury 12C causes
      significantly more symptoms in healthy volunteers than placebo. Questionnaires
      with a limited number of gross symptoms do not seem to be an appropriate
      methodological technique in drug proving research. If drug-proving phenomena
      exist, they appear to be rare.

PMID- 11327521
TI  - Homeopathy and conventional medicine: an outcomes study comparing effectiveness
      in a primary care setting.
AB  - BACKGROUND: Recent meta-analyses of randomized controlled trials in homeopathy
      have suggested that homeopathy is more than a placebo response. OBJECTIVE:
      Comparison of the effectiveness of homeopathy in primary care with conventional
      medicine in primary care for three commonly encountered clinical conditions.
      DESIGN: An international multicenter, prospective, observational study in a real
      world medical setting comparing the effectiveness of homeopathy with conventional
      medicine. PARTICIPANTS: Thirty (30) investigators with conventional medical
      licenses at six clinical sites in four countries enrolled 500 consecutive
      patients with at least one of the following three complaints: (1) upper
      respiratory tract complaints including allergies; (2) lower respiratory tract
      complaints including allergies; or (3) ear complaints. MAIN OUTCOME MEASURES: The
      primary outcomes criterion was the response to treatment, defined as cured or
      major improvement after 14 days of treatment. Secondary outcomes criteria were:
      (1) rate of recovery; (2) occurrence of adverse events; (3) patient satisfaction;
      and (4) length of consultation. RESULTS: Four hundred and fifty-six (456) patient
      visits were compared: 281 received homeopathy, 175 received conventional
      medicine. The response to treatment as measured by the primary outcomes criterion
      for patients receiving homeopathy was 82.6%, for conventional medicine it was
      68%. Improvement in less than 1 day and in 1 to 3 days was noted in 67.3% of the
      group receiving homeopathy and in 56.6% of those receiving conventional medicine.
      The adverse events for those treated with conventional medicine was 22.3% versus
      7.8% for those treated with homeopathy. Seventy-nine percent (79.0%) of patients
      treated with homeopathy were very satisfied and 65.1% of patients treated with
      conventional, medicine were very satisfied. In both treatment groups 60% of cases
      had consultations lasting between 5 and 15 minutes. CONCLUSIONS: Homeopathy
      appeared to be at least as effective as conventional medical care in the
      treatment of patients with the three conditions studied.

PMID- 11327522
TI  - Nutritional quality of organic versus conventional fruits, vegetables, and
      grains.
AB  - OBJECTIVES: To survey existing literature comparing nutrient content of organic
      and conventional crops using statistical methods to identify significant
      differences and trends in the data. DESIGN: Published comparative measurements of
      organic and conventional nutrient content were entered into a database for
      calculation. For each organic-to-conventional comparison, a percent difference
      was calculated: (organic - conventional)/conventional x 100. For nutrients where
      there was adequate data, the Wilcoxon signed-rank test was used to identify
      significant differences in nutrient content as represented by the percent
      difference. Mean percent difference values were also calculated for each
      significant nutrient by study and by vegetable for the most frequently studied
      vegetables. The nutrient content of the daily vegetable intake was calculated for
      both an organic and conventional diet. RESULTS: Organic crops contained
      significantly more vitamin C, iron, magnesium, and phosphorus and significantly
      less nitrates than conventional crops. There were nonsignificant trends showing
      less protein but of a better quality and a higher content of nutritionally
      significant minerals with lower amounts of some heavy metals in organic crops
      compared to conventional ones. CONCLUSIONS: There appear to be genuine
      differences in the nutrient content of organic and conventional crops.

PMID- 11327523
TI  - The safety of low-dose Larrea tridentata (DC) Coville (creosote bush or
      chaparral): a retrospective clinical study.
AB  - OBJECTIVE: To determine whether internal use of low doses of Larrea tridentata
      tincture or topical applications of this traditional herbal medicine are safe.
      DESIGN: Retrospective review of all people prescribed Larrea for internal or for
      topical use over a 22-month period. SETTING/LOCATION: A general naturopathic
      practice in Sedona, Arizona. SUBJECTS: Thirteen patients were identified for whom
      Larrea tincture for internal use was prescribed. An additional 20 female and 3
      male patients were identified for whom an extract of Larrea in Ricinus communis
      (castor) oil for topical use was prescribed. No patient had any history of liver
      disease. INTERVENTIONS: Larrea was prescribed as part of the usual care of each
      patient. In all cases it was given as either part of a complex herbal formula
      individualized for each patient containing less than 10% Larrea tincture or as an
      extract in Ricinus oil for topical use. OUTCOME MEASURES: Serum liver enzyme
      levels as well as blood urea nitrogen and creatinine levels, glucose levels,
      electrolytes, bilirubin levels, iron levels, ferritin levels, lipid levels, and
      complete blood count (CBC) were available for analysis in four patients; general
      clinical history and physical examination findings were relied on in all other
      cases. RESULTS: The four patients with complete before and after blood chemistry
      panels and CBC had no indication of liver damage from use of Larrea. This
      included one patient who was taking medications with significant potential for
      hepatotoxicity. No patient in the study, whether using Larrea for short term or
      long, internally or externally, showed any sign of organ damage during the period
      of follow-up. CONCLUSIONS: Relatively small intakes of Larrea tincture, or
      topical application of extracts in Ricinus oil, are safe when prescribed by a
      clinically trained botanical prescriber. Larrea should be used with caution in
      persons with a history of previous, or current, liver disease. It may be
      preferable to avoid the use of Larrea capsules because they have been associated
      with potentially dangerous overdosing.

PMID- 11327525
TI  - Surveys of complementary and alternative medicine: part I. General trends and
      demographic groups.
AB  - Data from the surveys of the Harvard team, led by David Eisenberg, M.D., are
      frequently used as a summary first paragraph introduction to the status of
      complementary and alternative medicine (CAM) in the United States. However, there
      is now a substantial body of literature on various facets of CAM use. Six
      national surveys to date are briefly discussed and summarized in a table. Some
      surveys have been conducted at a regional level. Three are summarized but there
      are too few data yet to draw any conclusions. Eighteen more exploratory surveys
      of specific subpopulations are presented to help draw a clearer picture of
      income, ethnic, and age groups. The search strategy is provided. The changing
      terminology in the field, the development of the CAM survey, and some common
      shortcomings are also addressed.

PMID- 11327524
TI  - Strychnos nux-vomica extract and its ultra-high dilution reduce voluntary ethanol
      intake in rats.
AB  - OBJECTIVES: To see whether Strychnos nux-vomica extract (mother tincture [MT]),
      its potency Nux 30c, and its principal alkaloid, strychnine, could reduce
      voluntary ethanol intake in rats. To analyze the solution structure of Nux MT,
      Nux 30c, 90% ethanol, and ethanol 30c by means of electronic (ES) and nuclear
      nuclear magnetic resonance (NMR) spectra. DESIGN: Potentially alcoholic rats were
      first given 20% ethanol and then kept on a two-choice bottle, one with 20%
      ethanol and another with tap water. These rats were given the following oral
      treatments for 15 days: group 1, control; group 2, strychnine at 0.36 mg/kg per
      day; group 3, ethanolic extract of S. nux-vomica seeds (Nux MT) at 3.6 mg/kg per
      day; and group 4, Nux 30c at 0.05 mL/d per rat. Nux 30c was prepared by
      successive dilution of Nux MT and 90% ethanol (1:100) and sonication at 20 kHz
      for 30 seconds in 30 steps. RESULTS: Both Nux MT and Nux 30c significantly
      reduced ethanol intake and increased water intake in rats. ES of two dilutions of
      Nux MT and Nux 30c showed intersections at more than one point suggesting
      existence of molecular complexes. ES of Nux MT in CCl4 showed a red shift when
      90% ethanol was added indicating molecular complexation and charge transfer
      interaction between ethanol and Nux compounds. NMR spectra of Nux MT, 90%
      ethanol, ethanol 30c, and Nux 30c indicated a change in solution structure of the
      medium (90% ethanol) of Nux 30c. CONCLUSION: Nux MT and Nux 30c could reduce
      ethanol intake in rats. The altered solution structure of Nux 30c is thought to
      mimic Nux MT and produce ethanol aversion in rats.

PMID- 11327526
TI  - Imaging of acute cervical spine trauma.
AB  - Over the past 15 years there have been dramatic changes in the approach to
      imaging acute cervical spine trauma. This article addresses the current thoughts
      and controversies regarding the most appropriate techniques to evaluate the
      patient with cervical spine trauma, with an emphasis on the role of computed
      axial tomography (CT) and magnetic resonance imaging (MRI). The issue of clinical
      versus radiographic evaluation of low-risk patients is also discussed.

PMID- 11327527
TI  - Thoracic and lumbar spine trauma.
AB  - Complete thoracolumbar trauma evaluation incorporates radiographs, computed
      tomography, and magnetic resonance imaging. Primarily to localize the level of
      injury, diagnosis of thoracolumbar spine trauma begins with radiographs. Computed
      tomography with sagittal reformatted images is more sensitive for identifying the
      full extent of injury and the degree of involvement of the bony posterior
      elements. Magnetic resonance imaging is used for evaluating the extent of soft
      tissue injury, including damage to ligaments, discs, and epidural spaces.
      Magnetic resonance imaging is most frequently performed when radiographs and
      computed tomography do not explain the patients' symptoms and when there is a
      possibility of epidural hematoma, traumatic disc herniation, or spinal cord
      injury.

PMID- 11327528
TI  - Imaging of acute head injury in the adult.
AB  - Head injury is a leading cause of trauma deaths. Prompt recognition of treatable
      injuries is critical to reduce mortality. Computed tomography (CT) of the head is
      readily obtainable in most medical centers, and is the cornerstone of rapid
      diagnosis. This article explains the important prognostic features of various
      forms of head trauma and their manifestations on noncontrast head CT. Intra-axial
      lesions are considered first, with explanation of diffuse axonal injury,
      contusions, and parenchymal hematomas. Extra-axial hemorrhages are also detailed,
      including subdural hematomas, epidural hematomas, and subarachnoid hemorrhage.
      Finally, extracranial manifestations of head trauma are explained, with
      descriptions of craniofacial fractures and orbital injuries. This article should
      help to place the imaging features of head trauma in clinical perspective for
      those involved in caring for trauma victims from a diagnostic or therapeutic
      standpoint.

PMID- 11327529
TI  - Cerebrovascular trauma.
AB  - Cerebrovascular trauma includes a wide variety of injuries, including
      dissections, traumatic aneurysms, arteriovenous fistulas, and vascular
      occlusions. These entities, which are often underdiagnosed, can produce
      devastating neurologic complications. This article reviews the clinical and
      radiographic presentations of vascular trauma to increase awareness of these
      injuries and improve our ability to detect and treat them.

PMID- 11327530
TI  - Imaging of head trauma in infancy and childhood.
AB  - Neurologic trauma is one of the most common and challenging problems encountered
      in the pediatric emergency setting. Early and accurate diagnosis is essential to
      minimize morbidity and mortality. The primary goal of the neuroimager in the
      acute setting is to provide rapid diagnosis, to monitor the development of
      complications, and to aid in the determination of prognosis. Unique features of
      the immature brain and skull influence the patterns and types of injuries
      observed. It is incumbent on the radiologist to understand these features as an
      aid to diagnosis. Further, the radiologist must be aware of the pathophysiology
      and appearance of nonaccidental trauma to ensure recognition of this devastating
      problem. Lastly, the radiologic tools available, their appropriate use, and their
      limitations should be understood by the entire trauma team to provide cost
      effective and timely care. This article summarizes the pathophysiology and
      current imaging of neurotrauma in the pediatric population, including trauma,
      nonaccidental trauma, accidental anoxic injury, and birth injury.

PMID- 11327531
TI  - PS2 protein in breast carcinomas: cut-off value of estrogen-regulated expression.
AB  - This study includes 152 patients with histologically confirmed breast carcinoma.
      Steroid hormone receptors (SR), estrogen (ER) and progesteron (PR) receptors, and
      pS2 protein were assayed on the same cytosolic extract in accordance with the
      recommendation of EORTC. Our results showed menopausal- and histologic grade
      related expression of pS2 protein. Unfavorable carcinoma subgroups, in relation
      to expression of pS2 protein were defined: postmenopausal carcinomas with
      histologic grade II, and pre-, as well as postmenopausal carcinomas with
      histologic grade III. There were overlappings of individual pS2 protein values
      between favorable and unfavorable carcinoma subgroups in relation to the
      expression of pS2 protein. Otherwise, no overlapping of pS2 protein values was
      obtained between ER-positive and ER-negative carcinomas within defined
      unfavorable menopausal - and histologic grade-related expression of pS2 protein
      subgroups. The highest pS2 protein level observed in ER-negative unfavorable
      subgroups (15 ng/mg) was considered as the cut-off value which defined estrogen
      regulated expression of pS2 protein.

PMID- 11327532
TI  - Influence of quercetin on B16 melanotic melanoma growth in C57BL/6 mice and on
      activity of some acid hydrolases in melanoma tissue.
AB  - Quercetin (QC) (5, 7, 3', 4' -tetra oxyflavonolol) is an ubiquitous flavonoid in
      many plants. The influence of QC on the growth of B16 melanotic melanoma in
      C57BL/6 mice and activity of some acid hydrolases in the tumor homogenates were
      investigated. Two series of experiments were carried out: In the first
      experimental group mice were inoculated s.c. with 10(6) of tumor cells (TC)
      suspended in 1 ml of saline. TC were obtained from the current serial passages.
      In the second series of experimental group mice were inoculated with melanoma
      cells preincubated 15 min. in different concentrations of QC. Mice of both series
      were divided into three subgroups. Mice of the first series were treated with QC
      i.p. every second day in a dose of 0.1 mg, 0.5 mg or 1.0 mg (total dose of 1.0
      mg, 5.0 mg or 10.0 mg per mice). Animals of the second series did not obtain any
      treatment. After the nineteenth day of experiment the mice were killed, tumors
      excised and weighed. Tumor tissue pieces were homogenized for enzyme activity
      determination. Fragments of tumor tissue were taken for electron microscopy (EM)
      investigation. In mice injected i.p. with QC mean tumor weight was significantly
      higher than in control I. The mean tumor weight in the first experimental group
      was higher than in control from 170% to 196% and in the second experimental group
      from 69% to 147%. Enzymes activity was also higher in both experimental groups as
      compared to controls. Arylsulphatase activity in the first group was higher from
      102% to 144% and in the second one - from 97% to 115% than in control I. Acid
      phosphatase activity was higher from 100% to 155% in the first experimental group
      and from 56% to 161% in the second one. Cathepsin D activity was greater from
      133% to 333% and from 113% to 300%, respectively. EM studies revealed the
      presence of greater number of Golgi structures and primary lysosomes in
      experimental groups of tumors (mice treated with QC and mice with melanoma
      preincubated in QC). These results clearly indicate that QC significantly
      enhances melanotic melanoma growth and increases acid phosphatase and cathepsin D
      activity in these tumors. The mechanism of QC action on the melanotic melanoma is
      not fully understood and remains to be defined.

PMID- 11327533
TI  - Seasonal variation in estrogen and progesterone receptor levels in breast cancer-
      a factor in data interpretation.
AB  - It is still widely accepted that evaluation of estrogen and progesterone
      receptors (ER, PR) in breast cancer tissue is one of the basic predictive
      indicators of hormonal therapy success. Evaluation of hormonal receptors is
      usually done once at the time of biopsy or surgery on the breast regardless of
      the effect of time. In a retrospective evaluation of 1301 medical records of
      breast cancer patients the authors wanted to identify any time period dependence
      in quantitative or qualitative hormonal status. Steroid receptors were measured
      in breast cancer tissues by cytosol-based ligand-binding technique. The results
      suggest a strong time period dependence in hormonal status. In premenopausal
      patients simultaneous evaluation of ER/PR revealed an increased frequency of both
      positive receptors in the autumn months, and a decrease in the spring months. In
      postmenopausal patients, both positive receptors were found more likely in the
      summer months and both negative in the late winter months. Our results suggest
      that one evaluation of hormonal receptor status does not necessarily provide an
      accurate estimate of the hormonal status in breast cancer patients.

PMID- 11327534
TI  - Radiation-induced apoptosis and cell cycle progression in TP53-deficient human
      leukemia cell line HL-60.
AB  - Human promyelocytic leukemia (HL-60) cells were irradiated with 0.5-100 Gy of
      gamma radiation and studied for 48 h post irradiation to determine the mode of
      death and progression of cells through the phases of the cell cycle. HL-60 cells
      are much more sensitive to radiation-induced loss of clonogenicity (D0 = 2.2 Gy)
      than to induction of apoptosis at 6 h (D0 for nonapoptotic cells = 32.6 Gy).
      After doses 20-50 Gy, the onset of massive apoptosis occurred and nonapoptotic
      cells were in G1/G0 phase of the cell cycle. In contrast, 6 h after irradiation
      with doses 2.5-10 Gy maximum cells were in S-phase and 16-24 h after irradiation
      were arrested in G2-phase. Maximum apoptosis occurred 48 h after irradiation with
      doses 3.5-10 Gy, and cells that died by necrosis were found in 9-44%.

PMID- 11327535
TI  - Intensive cyclic chemotherapy with unprocessed whole blood support in advanced
      breast cancer.
AB  - The aim of our project was to compare the efficacy of mobilised whole blood
      versus cryopreserved PBPC (peripheral blood progenitor cells) obtained by
      leukapheresis in the support of hematopoietic recovery in cyclic intensive
      chemotherapy. Twenty-nine women with breast carcinoma were treated. The mean age
      was 46 years. In stage III were 23, in stage IV were 6. They received 6 cycles of
      epirubicin 150 mg/m2 and cyclophosphamide 1250 mg/m2. In the first cycle, 24
      hours after chemotherapy, application of G-CSF 5 microg/kg/day was started, and
      discontinued when leukaphereses and whole blood collections were done.
      Leukapheresed progenitors were then divided into 3 aliquots, cryopreserved and
      reinfused after the 4th, 5th and 6th chemotherapy cycles. Mobilised whole blood
      was collected on day 14 of the 1st and 2nd cycles and reinfused 24 hours after
      chemotherapy. The occurrence of grade IV leukopenia was 1.82 times higher with
      whole blood support and grade IV thrombocytopenia 2.64 times higher than in
      cycles with cryopreserved PBPC support. This resulted from the fact that in one
      application the numbers of CD34+ cells and CFU-GM were nearly double in
      cryoconcentrates. The yields of CD34+ cells in 450 ml of whole blood were 1.8 x
      10(6)/kg, which is not sufficient for optimal hemopoietic recovery.

PMID- 11327536
TI  - Peripheral progenitor cells (PBPC) in supportive care after high-dose
      chemotherapy in breast cancer.
AB  - Hemopoietic growth factors (HGF) and leukapheresed peripheral progenitor cells
      (PBPC) are increasingly used for supportive care in high-dose chemotherapy (HDC)
      of solid tumors. Presently, therapeutic protocols with cyclic HDC plus PBPC
      support are successfuly used in breast cancer patients. Administration of PBPC
      significantly influences hemopoietic recovery in terms of shortening the
      pancytopenia period which reduces the risk of dangerous complications, especially
      the risk of infection. As a certain controversy exists about efficacy of this
      therapy, large randomized studies are conducted to find more accurate
      conclusions. In 1998 National Cancer Institute (NCI) gave top priority to four
      randomized studies of HDC with PBPC support. In recent years, rising yields of
      PBPC are obtained. The use of new combinations and dosages of hemopoietic growth
      factors leads to a significant increase of progenitor cells circulating in
      peripheral blood. Effective mobilization regimens combinations of chemotherapy
      and cytokines - enable to increase the numbers of circulating progenitors as much
      as 100-fold. Another aspect, how to minimize the risks is to reduce the
      transplant volume and so reduce the amount of cryoprotective agent DMSO (dimethyl
      sulfoxide) and hemolysed erythrocytes. This led to the idea to use only whole
      blood enriched for PBPC. At present it has been used also in our patients. The
      results show that enriched whole blood can be used as sufficient substitution for
      support in intensive cyclic chemotherapy in breast cancer patients.

PMID- 11327537
TI  - Estimation of changes in tubulin induced with etoposide in human leukemia cells
      line K-562 by immunofluorescence microscope.
AB  - This study was undertaken to examine the influence of etoposide on the
      distribution of tubulin in cells of human leukemia cell line K-562 by using
      immunofluorescence method. The cells were cultured with 5 different doses of
      etoposide: 0.2, 2, 20, 200, 2000 microM/ml. Changes in tubulin were dependant on
      concentration of the drug compared to untreated control cells. The changes
      occurred in distribution of tubulin in cells K-562 after treating them with 200
      and 2000 microM/ml etoposide. Cells treated with 200 microM/ml etoposide showed
      intense diffuse staining of the entire cells. At the surface of the cells there
      were also intensively stained structures extended outwards from the surface as
      lamellipodias. Cells cultured with 2000 microM/ml etoposide were much bigger from
      other cells exposed to lower doses of etoposide and control cells. Distribution
      of tubulin throughout these cells with diffuse intensive labeling of the cell
      periphery was seen. Very bright protrusions formed in lamellipodias at the
      surface of the cells were also observed.

PMID- 11327538
TI  - Biological activity of some 4-anilinoquinazolines: cytotoxic, genotoxic and
      antiprotease effects, induction of necrosis and changes of actin cytoskeleton.
AB  - Fourteen substituted 4-anilinoquinazolines have been tested for cytotoxic effect
      and structure activity relationships. The most active derivatives were
      substituted by chlorine or bromine group in the aromatic ring, in the pyrimidine
      ring by morpholine group and in the aniline skeleton by nitro group in position 4
      or 2. Derivatives 6-bromo-2-(morpholin-1-yl)-4-(4'-nitroanilino)quinazoline, 6
      bromo-2-morpholin-1-yl)-4-anilinoquinazoline, 2-(morpholin-1-yl)-4-(4'
      bromoanilino)-quinazoline and 6-chloro-2-(morpholin-1-yl)-4-(4'
      nitroanilino)quinazoline inhibited growth of tumor cell lines HeLa, B16 and
      L1210. Mutagenic data provided by Ames test showed, that the compounds 6-bromo-2
      morpholin-1-yl)-4-anilinoquinazoline and 2-(morpholin-1-yl)- 4-(4'
      bromoanilino)quinazoline did not exhibit the mutagenic effect, whereas the
      compounds 6-bromo-2-(morpholin-1-yl)-4-(4'-nitroanilino)quinazoline and 6-chloro
      2-(morpholin-1-yl)-4-(4'-nitroanilino) quinazoline increased slightly the number
      of revertants of the strain TA 98 without metabolic activation. Concentration 26
      micromol/L of 6-bromo-2-(morpholin-1-yl)-4-anilinoquinazoline induced necrosis of
      tumor cells B16. Concentration 5.2 micromol/l induced a significant increase of
      filamentous actin in the transformed HepG2 cells. Derivatives 6-bromo-2
      (morpholin-1-yl)-4-(4'-nitroanilino)quinazoline, 6-bromo-2-morpholin-1-yl)-4
      anilinoquinazoline, 2-(morpholin-1-yl)-4-(4'-bromoanilino)quinazoline and 6
      chloro-2-(morpholin-1-yl)-4-(4'-nitroanilino)quinazoline exhibited antiprotease
      effect on plasmine. This results could be relevant for the anticancer properties
      of these compounds.

PMID- 11327539
TI  - Signal-averaged electrocardiography in survivors of Hodgkin's disease treated
      with and without dexrazoxane.
AB  - Doxorubicin is one of the most effective anticancer drug, but its usefulness is
      limited by the risk of developing cardiomyopathy, cardiac dysfunction and
      ventricular arrhythmias. Dexrazoxane is used to protect against doxorubicin
      cardiotoxicity. It is uncertain whether the dexrazoxane-mediated cardioprotective
      effect will be reflected in electrophysiological properties of the heart. The aim
      of the present study was to evaluate the occurrence of frequency-domain signal
      averaged electrocardiographic (SAECG) abnormalities of the QRS complex and the
      initial ST segment in patients treated with and without dexrazoxane. Thirty
      children and young adults 2 months - 15 years after completion of doxorubicin
      containing therapy for Hodgkin's disease were evaluated with SAECG. Patients from
      group I (n = 13) received combined therapy with doxorubicin and dexrazoxane
      (DOX/DZX), patients from group II (n = 17) received doxorubicin without
      dexrazoxane (DOX). Using fast Fourier transformation within the QRS complex and
      the initial ST segment, area ratio (AR) values 40-100/0-40 Hz were calculated.
      Significant differences in these frequency parameters in the QRS complex between
      DOX/DZX group and DOX group (19.45+/-12.72 vs 46.18+/-43.06; p = 0.03) might
      indicate protective effect of dexrazoxane on electrophysiological myocardial
      properties.

PMID- 11327540
TI  - Cathepsin B and L and stefin A and B levels as serum tumor markers in squamous
      cell carcinoma of the head and neck.
AB  - Cysteine proteinases cathepsin (Cath) B and L and their endogenous inhibitors
      stefin (Stef) A and B concentrations were measured using a quantitative
      immunosorbent assay (ELISA; KRKA d.d., Novo mesto, Slovenia) in serum samples
      from 35 patients with primary and 7 patients with recurrent squamous cell
      carcinoma of the head and neck (SCCHN), obtained at diagnosis (Serum no.1) and
      after therapy (Serum no. 2), and compared to sera from 30 (Stef B, 90) healthy
      volunteers. A significantly higher Stef A (P = 0.005) and lower Stef B (P <
      0.001) concentrations were measured in patients' Serum no.1 than in controls, and
      the levels of Caths B and L and Stef A were found to be significantly elevated in
      Serum no.1 as compared to Serum no. 2 (P = 0.045, P = 0.041 and P = 0.024,
      respectively). The time of Serum no.2 collection did not influence the
      concentration of either Caths or Stefs in these samples, and no correlation was
      observed with the established prognostic factors for any of the parameters
      studied. Patients with subsequently diagnosed recurrent disease had a
      significantly lower Cath L concentration than those without evidence of relapse
      during follow up (P = 0.05). The risk of disease recurrence and SCCHN-related
      death correlated significantly with low Cath L serum levels (P = 0.012, P =
      0.006). The serum levels of Cath B, Stef A and Stef B did not influence
      significantly the probability of survival.

PMID- 11327541
TI  - The role of STIR MRI sequence in the evaluation of the breast following
      conservative surgery and radiotherapy.
AB  - The purpose of the study was to define the value of fat suppressed STIR sequence
      in the MRI of the conserved breast. To our knowledge, this study is the first
      clinical evaluation of STIR sequence in post-therapy conditions. Forty patients
      with early (T1-2, N0-1) invasive breast cancer underwent conservative surgery and
      postoperative radiotherapy. Routine follow-up examinations, including physical
      examination and mammography were supplemented with breast MRI in all cases 6-166
      months (mean 27.6) after initial treatments. Three patients had bilateral cancer.
      Including follow-up (9 patients) MRI examinations, altogether 53 MRIs were
      available for analysis. An 0.5 T MRI (Elscint, Haifa, Israel) was used with
      double breast coil. Axial T1 and T2 weighted spin echo, STIR and 3D gradient echo
      dynamic sequences were performed. Pre- and postcontrast slices underwent serial
      subtraction. Twenty-eight circumscribed lesions were identified. All were well
      visualised on STIR sequence, regardless of histologic nature of lesions. One low
      grade DCIS was not detected by any sequence. Differential diagnosis between
      benign and malignant lesions was not possible by STIR sequence alone. STIR
      sequence was found to be more sensitive in the detection of treatment related
      breast edema and fluid collection, than T2 SE (spin-echo) sequence. Even the
      patients who were not good candidates for subtracted contrast enhanced dynamic
      studies - because of motion artefacts - could have been examined with
      satisfactory results. STIR is a very sensitive sequence for depicting
      circumscribed lesions and post-therapy complications, but not suitable for
      differentiation. It is a useful tool in the follow-up of patients with conserved
      breast subjected to radiotherapy.

PMID- 11327542
TI  - The degree of bone marrow infiltration in patients with hairy cell leukemia
      treated with splenectomy compatible with long-term hematological remission.
AB  - To determine the degree of bone marrow infiltration with hairy cells which is
      compatible with long-term hematological remission in patients treated with
      splenectomy, we have investigated 7 patients surviving in hematological remission
      61 to 255 months (median 184 months) after splenectomy. As hematological
      remission has been considered absence of hairy cells (HCs) in the peripheral
      blood, normalization of peripheral blood cell counts (hemoglobin 120 g/l, white
      cell count 4.0 x 10(9)/l, absolute granulocyte count 1.5 x 10(9)/l, platelet
      count 100 x 10(9)/l) and absence of lymfadenopathy and any other activity of the
      disease. For detection of HCs a very sensitive method of immunostaining with
      monoclonal antibody DBA.44 in our own modification has been used. Low values of
      sIL-2R which is considered to be a non invasive marker of tumor burden and
      activity in HCL were in agreement with the opinion that the bone marrow was the
      only locality of tumor involvement in splenectomized patients. Infiltration up to
      20% with HCs (range 4% to 20%, median 10%) was found to be compatible with long
      term hematological remission and long-term overall survival. Patient (No 1) with
      30% infiltration of bone marrow with HCs, still normal peripheral blood cell
      counts, but a very high level of sIL-2R represents extraordinary finding which
      has been discussed in details.

PMID- 11327543
TI  - The importance of interstitial radiotherapy in the treatment of the base of
      tongue tumors: a retrospective analysis.
AB  - The authors have reviewed their experience with interstitial brachytherapy for
      the base of tongue cancer with the purpose of introducing treatment strategy and
      technique and presenting results. Between January 1993 and May 1999 twenty-one
      patients with primary squamous cell cancer of the base of tongue (T1-4N0-2) were
      treated by interstitial radiotherapy (RT). Seventeen patients with advanced stage
      cancer received brachytherapy (BT) boost after 60-66 Gy teletherapy and 4
      patients with early stage (T1-2N0) were managed by sole BT after tumor excision
      and elective neck node dissection in case of positive or very narrow (< 5 mm)
      margin. High-dose rate (HDR) after-loading unit (Ir-192 source) was used with
      rigid needles or flexible plastic tubes. The treatment plan was performed by
      PLATO 3D BT planning system. The mean dose of boost BT or sole BT was 20 Gy (12
      24 Gy) and 27 Gy (24-30 Gy), respectively. All treatments were delivered on
      consecutive days with a twice daily fractionation schedule, except the rigid
      needle technique (n = 4), where the dose was 12 Gy with a single fraction. After
      definitive RT of advanced stage disease, the rate of complete or partial
      remission was 65% (11/17) and 35% (6/17), respectively. At a mean follow-up time
      of 32 months the local tumor control for the entire patient population was 62%
      (13/ 21). Five patients (24%) died of local and/or regional failure and sixteen
      patients (76%) are alive (6 with local and/or regional disease and 10 without
      evidence of disease). All of the four sole BT treated patients belong to the
      latter group. The incidence of grade 2 or grade 3 mucositis was 48% and 52%,
      respectively. To achieve good local control with adequate doses, avoiding
      surgical morbidity and associated functional loss and to minimize late radiation
      sequelae, the combination of percutan and interstitial RT seems to be very
      advantageous in the treatment of the advanced tumor of the base of tongue. For
      patients with early stage (T1-2N0) cancer, sole postoperative BT of the tumor bed
      - by positive or very narrow margins - seems to be a feasible option. However,
      more patients and longer follow-up is required to define the value of sole BT.

PMID- 11327544
TI  - The efficacy of radiotherapy for vertebral hemangiomas.
AB  - Vertebral hemangiomas are benign, slowly growing tumors sometimes causing local
      pain in the spine and/or neurologic disorders. The present paper includes 14
      cases of painful vertebral hemangiomas treated by radiotherapy. All patients were
      irradiated using standard fractionation scheme with a total dose 20-30 Gy. One
      month after the treatment complete pain relief was noted in 36% of cases, five
      months later in 67% of cases, but in the remaining cases partial pain relief was
      noted. No correlation between treatment outcome and different biological and
      technical factors was found. No dose-response relationship was noted. The results
      suggest that anti-inflamatory effect of radiation plays the major role in this
      kind of treatment and that radiotherapy for vertebral hemangiomas is easy, short
      and highly effective analgetic treatment modality.

PMID- 11327545
TI  - Correlation between decreased type-II interleukin-1 receptor and increased
      monocyte chemotactic protein-1 expression in the endometrium of women with
      endometriosis.
AB  - PROBLEM: Monocyte chemotactic protein-1 (MCP-1), a potent inducer of macrophage
      recruitment and activation, is overexpressed in the eutopic endometrium of women
      with endometriosis. Eutopic endometrial cells of women with endometriosis secrete
      higher levels of MCP-1 than those of normal women, following stimulation with
      interleukin-1 (IL-1). The aim of this study was to examine whether there is any
      correlation between the expression of IL-1 receptor type II (IL-IRII), a specific
      downregulator of IL-1 activity, and that of MCP-1 in the eutopic endometrium of
      women with endometriosis. METHOD OF STUDY: Endometrial biopsies of 46 women with
      endometriosis and 22 healthy women were evaluated simultaneously for IL-1RII and
      MCP-1 expression by immunohistochemistry. RESULTS: Our study revealed a highly
      significant correlation between the decreased expression of IL-1RII and the
      increased expression of MCP-1 in the endometrial tissue of women with
      endometriosis (Spearman correlation coefficient r = -0.377, P = 0.002),
      particularly in the initial stages of the disease (stages I and II; r = - 0.368,
      P = 0.020 and r = -0.480, P = 0.002, respectively). Furthermore, this correlation
      was observed in the proliferative (r = -0.366, P = 0.047) and the secretory
      phases (r = -0.321, P = 0.049) of the menstrual cycle. CONCLUSIONS: These results
      suggest that the reduced capability of endometrial tissue to downregulate IL-1
      proinflammatory effects may be involved in the increased expression of MCP-1 in
      the endometrium of women with endometriosis and the establishment of an
      inflammatory state. The results also indicate a sustained process of cell
      activation throughout the menstrual cycle.

PMID- 11327546
TI  - Analysis of the CD4 protein on human vaginal T lymphocytes.
AB  - PROBLEM: Although T lymphocytes at the human vaginal mucosa have been partially
      characterized, there remains a paucity of information regarding cell-mediated
      immune mechanisms at this mucosal site. In mice and humans, there are several
      phenotypic distinctions between vaginal T lymphocytes and those in the peripheral
      circulation. Recently, we observed as well that the N-terminus of the CD4 protein
      on murine vaginal T lymphocytes is atypically expressed compared to its systemic
      counterpart, and that the atypical expression extends to the mRNA level. METHOD
      OF STUDY: The purpose of this study was to evaluate the CD4 protein on human
      vaginal T lymphocytes by flow cytometry and RT-PCR. RESULTS: Results showed that,
      in contrast to mice, the CD4 protein on human vaginal and peripheral blood T
      lymphocytes are similar at both the molecular and protein levels. CONCLUSIONS:
      These results indicate that based on several differences between human and mouse
      vaginal T cells, caution is urged when using mice as a model to study human
      vaginal immunity.

PMID- 11327547
TI  - Pregnancy-specific glycoproteins function as immunomodulators by inducing
      secretion of IL-10, IL-6 and TGF-beta1 by human monocytes.
AB  - PROBLEM: Low levels of pregnancy-specific glycoproteins (PSGs) in maternal serum
      have been correlated with complications of pregnancy. We investigated the ability
      of human PSGs to regulate in vitro production of cytokines. METHOD OF STUDY:
      Human monocytes and murine RAW 264.7 cells were treated with recombinant PSG1,
      PSG6, PSG11, or a truncated PSG6 consisting of only the N-terminal domain
      (PSG6N). Cytokine production in response to PSG-treatment was measured by ELISA
      and/or reverse transcriptase-PCR. RESULTS: All PSGs tested induced secretion of
      interleukin (IL)-10, IL-6 and transforming growth factor (TGF)-beta1 by both
      human and murine cells, but not IL-1beta, tumor necrosis factor (TNF)-alpha or IL
      12. The N-terminal domain of PSG6 was sufficient for induction of monocyte
      cytokine secretion. Induction of IL-10 and IL-6 was preceded by an increase in
      the specific mRNAs. CONCLUSIONS: PSG1, PSG6, PSG6N, and PSG11 induce dose
      dependent secretion of anti-inflammatory cytokines by human monocytes. Human and
      murine PSGs exhibit cross-species activity. Our results are consistent with a
      role for PSGs in modulation of the innate immune system.

PMID- 11327548
TI  - Plasma antiviral activity and interferon-gamma production by superantigen
      stimulated lymphocytes during normal human pregnancy.
AB  - PROBLEM: Plasma interferon (IFN)-beta levels, lymphocyte responsiveness, and
      evaluation of the relationship between circulating antiviral activity (AA) and
      IFN-gamma production were studied in pregnant women and nonpregnant age-matched
      controls with the objective of elucidating the downregulation of IFN-gamma
      production in successful pregnancy. METHOD OF STUDY: In plasma and supernatants
      of peripheral blood mononuclear cell (PBMC) cultures, stimulated with
      staphylococcal enterotoxin A (SEA) superantigen, from 43 pregnant women with a
      history of normal pregnancy and 30 healthy nonpregnant age-matched controls,
      levels of AA were measured in a micromethod by inhibition of the cytopathic
      effect (CPE) caused by vesicular stomatitis virus (VSV) in the human amnionic
      cell line (WISH). RESULTS: Significantly higher plasma AA (60% was IFN-gamma and
      residual activity was acid-labile IFN-like) was present in pregnant women than
      controls. On the other hand, SEA-activated PBMCs from pregnant women produced
      significantly lower IFN-gamma levels than those of nonpregnant women.
      Furthermore, maternal plasma AA levels correlated negatively with IFN-gamma
      production by SEA-stimulated PBMCs. CONCLUSION: The hypothesis that successful
      pregnancy requires downregulation of IFN-gamma is only partially sustained,
      suggesting that the immunology of pregnancy is more complex and that murine and
      human pregnancy have different cytokine profiles.

PMID- 11327549
TI  - Blocking antibodies in blood from patients with recurrent spontaneous abortion in
      relation to pregnancy outcome and intravenous immunoglobulin treatment.
AB  - PROBLEM: To study whether the occurrence of mixed lymphocyte culture (MLC)
      blocking antibodies is associated with pregnancy outcome in women with
      unexplained recurrent spontaneous abortion (RSA) and the in vivo effect of
      intravenous immunoglobulin (IVIG) treatment on MLC blocking effect. METHOD OF
      STUDY: Blood samples from 41 RSA patients were obtained before and after
      pregnancy, and blocking antibodies were estimated by one-way MLC assay. The
      patients received IVIG or placebo (saline) during pregnancy. Additionally,
      prepregnancy blood samples from 31 RSA women and 10 controls were obtained.
      RESULTS: We found no correlation between blocking antibodies before pregnancy and
      the pregnancy outcome. The occurrence of blocking antibodies was not affected by
      pregnancy or IVIG treatment. CONCLUSIONS: Blocking antibodies have no predictive
      value for the pregnancy outcome in RSA patients, and their production seems not
      to be affected by IVIG.

PMID- 11327551
TI  - Involvement of calpain for apoptosis in dysfunction of the unaffected testis in
      rats with experimental testicular torsion.
AB  - PROBLEM: The dynamics of calpain and involvement of apoptosis in sperm formation
      disorder of the unaffected testis in rats with experimental testicular torsion
      were investigated. METHODS OF STUDY: Using 6-week-old Wistar rats, an
      experimental unilateral testicular torsion model was prepared. The bilateral
      testes were excised 1, 3, 5, 7, 14, 35, and 70 days after the left testis was
      twisted, and the unaffected testes were subjected to immunohistological staining,
      sodium dodecyl sulfate polyacrilamide gel electrophoresis and Western blotting
      using anti-calpain antibodies. Apoptosis was detected by the TdT-mediated dUTP
      biotin nick end-labeling (TUNEL) method. RESULTS: By immunohistological staining,
      positive immunostaining by anti-pro mu-calpain antibody was observed in the
      spermatocyte nucleus, but not with anti-pro m-calpain antibody. The staining was
      increased until 7 days after testicular torsion, then decreased with progression
      of sperm formation disorder. By Western blotting, the intensity of staining with
      anti-pro mu-calpain antibody was increased until 7 days after torsion of the
      testis. Apoptosis expression in the unaffected testis was significantly inhibited
      by addition of a calpain inhibitor. CONCLUSIONS: It was suggested that mu-calpain
      may be involved in apoptosis expression in sperm formation disorder of the
      unaffected testis in unilateral testicular torsion.

PMID- 11327550
TI  - IgG anti-laminin-1 autoantibody and recurrent miscarriages.
AB  - PROBLEM: The present study assesses the clinical significance of anti-laminin-1
      auto-antibodies (auto-Abs) in recurrent miscarriages. METHOD OF STUDY: A total of
      207 recurrent aborters with a history of two or more consecutive first-trimester
      miscarriages were tested for the presence of anti-laminin-1 Abs, beta2
      glycoprotein I-dependent anticardiolipin Abs, lupus anticoagulants, anti-DNA Abs,
      and anti-nuclear Abs, before they had conceived again. Recurrent aborters then
      were followed up during subsequent pregnancies and their outcomes were evaluated
      relative to their blood test results prior to pregnancy. RESULTS: Fifty-five
      (31.1%) women out of 177 recurrent aborters were positive for IgG anti-laminin-1
      auto-Abs. The levels of IgG anti-laminin-1 auto-Abs in recurrent aborters were
      significantly higher than those in healthy pregnant women and in healthy non
      pregnant women (P = 0.0043 and 0.0073, respectively). The live birth rate of
      subsequent pregnancies in IgG anti-laminin-1 auto-Abs-positive recurrent aborters
      was significantly lower than the IgG anti-laminin-1 auto-Abs-negative recurrent
      aborters (P = 0.0320). There were no specifically significant relationships
      observed between IgG anti-laminin-1 auto-Abs and other tested auto-Abs.
      CONCLUSION: IgG anti-laminin-1 auto-Abs are associated with recurrent
      miscarriages and the subsequent pregnancy outcome of recurrent aborters.

PMID- 11327553
TI  - Bulging disks.

PMID- 11327552
TI  - Image analysis of the effects of gonadectomy on colloidal carbon uptake in vivo
      by sinusoidal cells in liver and spleen of the mouse.
AB  - PROBLEM: The presence of androgen and estrogen receptors in macrophages was
      recently described. This suggests that both sex hormones directly act on
      reticuloendothelial system (RES) activity. Studies of the effect of gonadectomy
      on uptake and clearance of foreign materials make clear a role of the testis and
      ovary in RES regulation. However, there is still some disagreement as to the
      gonadal influence on RES. METHOD OF STUDY: We applied a computed image analysis
      system to the investigation of the effects of gonadectomy on colloidal carbon
      uptake by the liver and spleen sinusoidal cells in mice. Mice were gonadectomized
      or sham-operated. After a few weeks, they received colloidal carbon with or
      without pretreatment with lipopolysaccharide (LPS). Thereafter, livers and
      spleens were taken for quantitative determination of the amounts of endocytosed
      carbon in the sinusoidal cells by means of digital image analysis. RESULTS:
      Ovariectomy did not significantly affect hepatic and splenic RES activities
      compared with sham-operated controls. Treatment of mice with LPS after
      ovariectomy also caused no significant changes of the RES activities compared
      with sham-operated and LPS-injected controls. In contrast, orchidectomy resulted
      in significant enhancement of splenic RES activity compared with sham-operated
      males, while hepatic RES activity did not significantly change with orchidectomy
      alone. However, LPS treatment to orchidectomized mice significantly augmented
      both hepatic and splenic RES activities compared with sham-operated and LPS
      injected controls. CONCLUSION: The significant augmentation of RES activity by
      orchidectomy, but not by ovariectomy, indicates that male RES activity is
      physiologically downregulated in the presence of the testes. Furthermore, splenic
      RES is more sensitive to orchidectomy than hepatic RES.

PMID- 11327554
TI  - Effect of gender, age, and anthropometry on axial and appendicular muscle
      strength.
AB  - OBJECTIVE: To assess age and gender differences in muscle strength. DESIGN: The
      strength of back extensors, upper limbs (grip), and lower limbs (knee extensors)
      was measured. Anthropometric measurements and body mass index also were assessed.
      RESULTS: Group comparisons were made for each decade. Back extensor strength
      (BES) in subjects aged 20 to 89 yr ranged from 93 to 832 N in men and from 71 to
      440 N in women. BES peaked in the fourth decade for men and in the fifth decade
      for women. When the two genders were compared, muscle strength in women was less
      than that in men at all ages. At different decades, women's BES ranged from 54%
      to 76% compared with that of men's BES. There was a 64% loss of BES in men from
      the peak in their fourth decade (556 N) to the lowest level in their ninth decade
      (201 N). Women experienced a 50.4% loss from the peak in their fifth decade (306
      N) to the lowest level in their ninth decade (152 N). CONCLUSIONS: Men had a
      greater loss of BES than women with increasing age. In both genders, there was
      more loss of BES than appendicular muscle strength. Reduction in BES in women
      coincided with increased body mass index in older age. In women, there was a
      negative correlation between body weight and level of physical activity, whereas
      this finding was not evident in men. Background factors related to a higher
      incidence of back pain, falls, and fractures, especially in women, may be a
      reduction in muscle strength, along with increasing age and body mass index. This
      cross-sectional study showed that physiologic reduction of muscle strength, which
      began early in life, later stopped and that muscle strength even improved,
      despite the aging process. Therefore, initiating strengthening exercises at any
      age is encouraged to prevent the impact of several age-related musculoskeletal
      challenges.

PMID- 11327555
TI  - Insomnia screening in postacute traumatic brain injury: utility and validity of
      the Pittsburgh Sleep Quality Index.
AB  - OBJECTIVE: To assess insomnia in a rehabilitation population, the authors
      examined the utility and validity of the Pittsburgh Sleep Quality Index (PSQI).
      The assessment of insomnia is relevant to the treatment of traumatic brain injury
      at the postacute level and routine screening for insomnia may be enhanced by the
      availability of a standardized, conveniently used, self-report sleep
      questionnaire. DESIGN: The authors prospectively studied 91 consecutive patients
      with traumatic brain injury who were admitted to an outpatient
      neurorehabilitation program. Besides administering the PSQI, Beck Depression
      Inventory, Epworth Sleepiness Scale, and Multidimensional Pain Inventory, sleep
      diary and interview data were obtained and used to divide subjects into insomnia
      and noninsomnia groups according to the criteria established by the Diagnostic
      and Statistical Manual of Mental Disorders, ed 4. RESULTS: Sensitivity and
      specificity rates to the clinical diagnosis of insomnia were 93% and 100%,
      respectively, for a PSQI Global Score of >8, and 83% and 100% for a diagnosis of
      insomnia based exclusively on PSQI-derived sleep variable data. Sleep diary data
      provided concurrent validity for PSQI estimates of sleep-onset latency, sleep
      duration, and sleep efficiency. The Beck Depression Inventory, Epworth Sleepiness
      Scale, and Multidimensional Pain Inventory established concurrent validity for
      individual PSQI items pertaining to mood, hypersomnia, and pain disturbance.
      CONCLUSION: The PSQI was demonstrated to be a valid and useful screening tool for
      assessing insomnia among postacute patients with traumatic brain injury.

PMID- 11327556
TI  - Incidence of neurologic deficits and rehabilitation of patients with brain
      tumors.
AB  - OBJECTIVE: To report and discuss common neurologic problems in adults with brain
      tumors admitted for inpatient rehabilitation at an acute rehabilitation center.
      DESIGN: Retrospective, descriptive, case series of 51 consecutive adult patients
      (65% male), with a variety of tumor types (31.3% glioblastoma, 25.5% meningioma,
      and 25.5% metastatic). Outcome measures were the functional status as measured by
      the FIM scores, the length of rehabilitation stay, and discharge dispositions.
      RESULTS: The most common deficit was impaired cognition (80%), followed by
      weakness (78%), visual-perceptual deficit (53%), sensory loss (38%), and bowel
      and bladder dysfunction (37%). Less common problems, in decreasing incidence,
      were cranial nerve palsy, dysarthria, dysphagia, aphasia, ataxia, and diplopia.
      Thirty-eight (74.5%) patients had three or more concurrent neurologic deficits,
      and 20 (39.2%) patients had five or more deficits. Concurrent deficits among
      patients with hemi- and tetraparesis involved cognition (n = 29 patients), visual
      perceptual function, sensation, cranial nerve palsy, and neurogenic
      bowel/bladder. The average admission FIM score of 67.2 increased to 87.1 at the
      time of discharge, with similar gains between patients with primary brain tumor
      and metastatic disease. Thirty-five patients were discharged home, seven to a
      nursing home, and one to hospice care; there were eight acute transfers.
      CONCLUSIONS: Impaired cognition, weakness, and visual-perceptual deficits were
      the most common problems in this study population. Our study supports the
      benefits of comprehensive and interdisciplinary rehabilitation for patients with
      primary as well as metastatic brain tumors.

PMID- 11327557
TI  - A neuromuscular test battery for osteoporotic women: a pilot study.
AB  - OBJECTIVE: To examine the efficacy of a short neuromuscular test battery in
      elderly women suffering from osteoporosis in accordance with the World Health
      Organization criteria, with and without a history of fractures. Reduced bone mass
      and a high likelihood of falling increase the risk of osteoporotic fractures.
      There is a need for neuromuscular tests to identify individuals at risk for falls
      and fractures. DESIGN: The women were assessed twice. Forty-two women, with a
      mean age of 70.0 +/- 5.1 (SD) yr, completed the first assessment. The number of
      postmenopausal fractures and the women's history with regard to agility and falls
      were assessed. The women performed neuromuscular tests (one-leg stance, tandem
      walk, and body sway); bone mineral density of the spine and femoral neck were
      measured. For the follow-up assessment, 13.2 +/- 1.3 mo later, 39 women were
      studied. The same outcome measurements were obtained at both evaluations.
      RESULTS: During the observation period, five women fell once and one woman fell
      twice; there were only two vertebral fractures and no nonvertebral fracture.
      Neuromuscular performance did not change during this observation period. The
      median changes in bone mineral density between the two assessments were
      clinically not relevant. A comparison between patients suffering from established
      osteoporosis and osteoporotic patients without a history of postmenopausal
      fractures showed that both groups of patients did not differ with respect to age,
      neuromuscular performance, bone mineral density, and fear of falling. CONCLUSION:
      This neuromuscular test battery is a feasible and practical tool because it is
      brief and economical to perform. However, its efficacy as a predictor of
      fractures must be tested in additional studies with a long-term follow-up and a
      larger group of subjects.

PMID- 11327558
TI  - Deterioration of balance control after limb-saving surgery.
AB  - OBJECTIVE: Evaluation of the changes in balance control observed in patients
      after limb-saving surgery for malignant tumors of the lower limb. DESIGN: Case
      series. RESULTS: In 11 patients who underwent limb-saving surgery and 10 healthy,
      age-matched controls, displacement of the amplitude of the center of pressure
      (ACP) and velocity of the center of pressure (VCP) during normal standing and
      standing on a balance board were registered. Adding such constraints as standing
      with eyes closed and performing a Stroop task made standing more complex. During
      normal standing and on the balance board, both groups showed comparable ACP and
      VCP values. With eyes closed, both patients and controls showed a higher
      amplitude and velocity in the anterior-posterior direction. In the patient group,
      the Stroop task affected the ACP (4.5 +/- 0.8 mm) compared with normal standing
      (2.9 +/- 0.4 mm) and VCP (18.6 +/- 3.0 mm/sec) compared with normal standing
      (11.9 +/- 1.0 mm/sec). During balance board standing, the authors found a
      difference in the VCP for both groups whose eyes were closed and who performed
      under dual-task conditions (controls, 23.2 +/- 3.3 and 14.9 +/- 2.9 mm/sec;
      patients, 80.1 +/- 12.9 and 23.6 +/- 3.4 mm/sec). CONCLUSIONS: Although the
      patient group showed impressive upright standing after limb-saving surgery,
      upright standing become more difficult under higher visual and cognitive loads.
      This finding indicates that the level of postural automatism is not complete in
      these patients.

PMID- 11327559
TI  - Gunshot versus nongunshot spinal cord injury: acute care and rehabilitation
      outcomes.
AB  - OBJECTIVE: To examine the impact of gunshot-caused spinal cord injury on acute
      and rehabilitative care outcome using a case control design. DESIGN: Two groups
      (i.e., gunshot- vs. nongunshot-caused spinal cord injury) of 212 individuals were
      matched case-for-case on age (i.e., within 10 yr), education, gender, race,
      marital status, primary occupation, impairment level, and Model System region.
      Outcome measures included length of hospital stay, functional status (FIM),
      treatment charges, and home discharge rates. RESULTS: The two groups did not
      differ in the length of stay during acute and rehabilitative care, charges during
      rehabilitative care, or postrehabilitation discharge placement. Several
      significant between-group differences in treatment procedures were noted (e.g.,
      prevalence of spinal surgery), which may, in part, account for the higher acute
      care charges among those persons with nongunshot-caused spinal cord injury.
      CONCLUSION: Once an individual is stabilized and admitted for rehabilitative
      care, gunshot etiology of spinal cord injury seems largely unrelated to the
      initial rehabilitation outcome.

PMID- 11327561
TI  - Ulnar nerve conduction velocity as function of wrist position.
AB  - Ulnar nerve conduction velocity (CV) calculated across the elbow has been shown
      to be significantly influenced by the position of the elbow. This study
      investigated the effect of wrist position on ulnar nerve CV in 19 control
      subjects. Ulnar nerve CV was determined with the elbow flexed at 90 degrees at
      two different wrist positions. The below-elbow-to-wrist CV was not significantly
      different between the wrist extended and the wrist flexed. Similarly, the mean
      across-elbow CV with wrist extended was not significantly different from the CV
      with the wrist flexed. The authors conclude that wrist position does not affect
      the calculated ulnar nerve CV across the elbow.

PMID- 11327560
TI  - Selectivity and sensitivity of intramuscular and transcutaneous electromyography
      electrodes.
AB  - We evaluated the differences in selectivity and sensitivity of intramuscular fine
      wire electrodes and transcutaneous electrodes in detecting dynamic
      electromyography (EMG) signals from extensor digitorum (EDC) and extensor carpi
      radialis (ECR) muscles during isolated EDC and ECR contractions in two able
      bodied subjects. Intramuscular fine-wire electrodes differentiated EDC and ECR
      EMG activities better than transcutaneous electrodes, and intramuscular fine-wire
      electrodes recorded higher amplitude signals than transcutaneous electrodes. Data
      suggest that intramuscular fine-wire electrodes are more selective and sensitive
      than transcutaneous electrodes in detecting EMG signals from adjacent forearm
      muscles.

PMID- 11327562
TI  - Intrathecal baclofen for spasticity caused by thrombotic stroke.
AB  - This study was undertaken to determine the efficacy of intrathecal baclofen
      therapy in patients who suffer spasticity after a stroke. This case involves a 64
      yr-old woman whose thrombotic strokes resulted in severe left-upper and lower
      limb spasticity. The patient achieved substantial functional gains as well as
      improved ease of care, quality of life, and cessation of narcotic use.

PMID- 11327563
TI  - Lumbosacral pain in an athlete.
AB  - This report presents a case of a stress fracture in the sacrum. The diagnosis of
      a stress fracture in the sacrum is an uncommon localization and has been reported
      infrequently in the English literature. Association of this type of stress
      fracture with a pneumatocyst has not previously been reported.

PMID- 11327564
TI  - Ethical implications of outcomes research.

PMID- 11327565
TI  - Describing paraspinal electromyographic findings.

PMID- 11327566
TI  - Multiple frequency steady-state evoked magnetic field mapping of digit
      representation in primary somatosensory cortex.
AB  - Magnetic source imaging of multiple frequency steady-state somatosensory evoked
      responses was examined using a 151-channel magnetoencephalography (MEG) system
      and a dual-channel electrical stimulator. Somatotopy of digit representation was
      studied in healthy subjects and effects of injury-related cortical plasticity in
      patients with unilateral transections of the median or the ulnar nerve. Dipole
      source locations exhibited somatotopic order with overlap between neighboring
      digits. In two of three nerve injury patients evidence for cortical
      reorganization was found. The location of sources related to digits neighboring
      deafferented digits was changed and their dipole moments were enlarged by
      comparsion with the sources related to contralateral homologue control digits. As
      a basis for magnetic source imaging, the recording of multiple frequency
      somatosensory steady-state evoked responses may be a viable and time saving
      alternative to the recording of transient evoked responses.

PMID- 11327567
TI  - Somatotopic organization and cortical projections of the ventrobasal complex of
      the flying fox: an "inverted" wing representation in the thalamus.
AB  - The present study investigates the somatotopic representation in the
      somatosensory thalamus of a megachiropteran bat. Using standard microelectrode
      mapping techniques, representational maps were generated for the ventrobasal (Vb)
      and posterior (Po) thalamic complexes of the Grey-headed flying fox. Anatomical
      tracing from neocortical injections provided additional data confirming the
      somatotopy found physiologically. A full representation of the body surface
      innervated by the trigeminal and spinal nerves was found. However, in contrast
      with other mammals, the representations of the forelimb and adjacent thoracic
      trunk within the thalamus were inverted. This means that the distal portions of
      the wing membrane and the tips of the digits were represented dorsally in Vb, and
      the thoracic trunk was represented ventrally. In Po the digit tips were
      represented in the ventral most portion and the thoracic trunk in the dorsal
      portion of the nucleus. These results are discussed in relation to similarities
      of megachiropteran somatosensory thalamic nuclei to those of other mammalian
      species and in relation to the formation of thalamic somatotopic maps and fiber
      sorting.

PMID- 11327568
TI  - How separate are the sensory, emotional, and motivational dimensions of pain? A
      multidimensional scaling analysis.
AB  - To map the structure of the space generated by verbal descriptors of pain, 41
      male college students made pairwise similarity judgments to all possible pairings
      of 16 words that describe experiences commonly associated with noxious electrical
      stimulation. Individual Differences Scaling (INDSCAL) yielded four dimensions (D)
      in the group stimulus space: D-1, Intense to Moderate Experiences, contained two
      attributes: Strong Sensations and Strong Emotions; D-2, Moderate to Weak
      Experiences, exhibited two attributes: Moderate Sensations and Moderate Emotions;
      D-3, Motivational State, possessed two attributes: Pain and Arousal Level; D-4,
      Sensory Qualities, exhibited two attributes: Pain and Somatosensory Qualities.
      The interpretation of the dimensions was supported by Preference Mapping
      (PREFMAP) and by correlations between subject weights and (a) psychological tests
      and (b) responses to noxious electrical stimuli. CONCLUSION: semantically, the
      pain attribute or component of the total pain-suffering experience pervades
      emotional, motivational and somatosensory attributes. Pain is not an independent
      dimension. This means that a score on a pain rating scale is not a pure measure
      of the patient's pain, but is heavily influenced in unknown ways by the patient's
      emotional and motivational state.

PMID- 11327569
TI  - Changes in potentiation and timing of sensorimotor transmission after adaptation
      of a postsynaptic transient outward current in a simulated cortical neuron.
AB  - How adaptation of a postsynaptic transient outward current might affect the
      efficacy of sensorimotor transmission was investigated. The transmission signals
      that were studied were a 5 ms conditioned stimulus (CS) and a 60 ms US drawn from
      intracellularly recorded, depolarizing postsynaptic potentials (PSPs) elicited in
      pyramidal neurons of the cat motor cortex by a click CS and a glabella tap US,
      respectively. SPICE, a program used to analyze electrical circuits, was used to
      simulate the cortical neuron containing the adaptive outward current. Changes in
      the magnitude and latency of rise to firing threshold of the PSPs were compared
      i) after presynaptic augmentation of a CS input in the absence of an adaptive
      postsynaptic current and ii) after decreasing the magnitude of an adaptive
      postsynaptic current that was rapidly activated by depolarization. Effects of
      short (6 ms) and long (24 ms) inactivation time constants of the postsynaptic
      current were also studied. In both presynaptic adaptation and postsynaptic
      adaptation, the potentiation of the magnitude of the CS-induced PSP was similar,
      with the latency to threshold being reduced by < or = 1 ms in both cases. The
      effects on the US PSP differed. Presynaptic adaptation affecting the CS had no
      effect on the US. Adaptation of the CS by a postsynaptic outward current with a 6
      ms inactivation time constant, reduced the latency to threshold of an EPSP from a
      nearby US synapse by up to 6 ms by augmenting the initial portion of the slowly
      rising US-induced PSP. Adaptation of a postsynaptic current with a 24 ms
      inactivation time constant reduced the latency of response to the US PSP by up to
      16 ms. When the US synapse was relocated to the soma, the reduction in US latency
      caused by adaptation of the outward current at the CS synapse was reduced by up
      to one half. The latency of slowly rising components of integrated synaptic
      responses to compound CSs of > 5 ms duration from multiple synaptic inputs would
      be expected to show reductions corresponding to those of the US. We conclude that
      potentiation of synaptic transmission by adaptation of a postsynaptic outward
      current can result in reductions of latency of sensorimotor transmission that can
      significantly affect the timing and accuracy of controlled motor tasks. These
      effects depend significantly on the locations of the synaptic inputs within the
      cell.

PMID- 11327570
TI  - The effects of heat-induced pain on the detectability, discriminability, and
      sensation magnitude of vibrotactile stimuli.
AB  - The effects of heat-induced pain on absolute thresholds, sensation magnitudes and
      amplitude-difference thresholds were measured at 10 and 100 Hz. Consistent with
      previous results, heat-induced pain elevated the absolute thresholds by
      approximately 8.0 dB and lessened the magnitudes of tactile sensations during
      pain as compared to the non-painful condition. In contrast to these effects, the
      discriminability of change in the intensity of the vibrotactile stimuli was
      unaffected by the presence of pain indicating that the effect of pain on tactile
      sensations is more likely due to sensory rather than cognitive processes (i.e.,
      attention) and that the mechanisms underlying tactile sensitivity as compared to
      discriminability are different.

PMID- 11327571
TI  - Haptic discrimination of size and texture in squirrel monkeys (Saimiri sciureus).
AB  - The present study analyzed haptic abilities of four squirrel monkeys. Using a two
      alternative forced-choice procedure, stimuli were presented in a visually opaque
      box, allowing unrestrained test subjects to grab through a small opening and
      touch the discriminanda. Difference thresholds were determined by a modified
      method of limits. In the first experiment we determined size difference
      thresholds for the discrimination of circular cylinders using standard stimuli
      differing in diameter from 10 mm to 35 mm. In the second experiment a texture
      difference threshold was obtained for the discrimination of grooved surfaces
      (groove width 2-7 mm). The squirrel monkeys achieved a mean size difference
      threshold of 8% stimulus difference. The linear increase of absolute thresholds
      as a function of the starting stimulus size showed that haptic size
      discriminations in squirrel monkeys correspond to Weber's law. Three of the
      animals achieved a texture difference of 10% stimulus difference, while one
      monkey showed a distinctively lower haptic acuity. An analysis of the exploratory
      behavior points to a subject-related difference in the significance of cutaneous
      and kinesthetic information during size discriminations. Whereas differences in
      the animals' exploratory behavior did not correlate with the size difference
      threshold a subject achieved, different thresholds for texture discrimination can
      be explained by the different exploratory procedures the monkeys used to touch
      grooved surfaces. The low difference thresholds determined for the squirrel
      monkeys in the present study point to the significance of unrestrained test
      conditions for the assessment of the haptic capacity of a species.

PMID- 11327572
TI  - Composition of the medial and posterior articular nerves of the mouse knee joint.
AB  - The number and the distribution of fiber size in the medial (MAN) and posterior
      (PAN) articular nerves of the mouse knee joint were studied by electron
      microscopy. The MAN contained 75 +/- 28 nerve fibers consisting of 63 +/- 24
      unmyelinated and 12 +/- 6 myelinated fibers. The PAN was composed of 195 +/- 50
      nerve fibers, namely 129 +/- 28 unmyelinated and 66 +/- 24 myelinated fibers. A
      skewed unimodal distribution of the unmyelinated nerve fiber diameters was seen
      in both nerves ranging from 0.1 to 1.2 microm with a maximum between 0.3 and 0.6
      microm. The myelinated nerve fibers in the MAN ranged from 1 to 8 microm with a
      peak between 2 and 5 microm. In the PAN, their diameters ranged from 1 to 12
      microm with a clearly visible peak at 4-5 microm and a plateau at 8-9 microm that
      may represent a second maximum. These data show that the knee joint innervation
      of the mouse is comparable to those of the cat and rat concerning the types of
      nerve fibers and the composition of the two nerves. However, in relation to the
      much smaller area of tissue to be innervated the total number of primary
      afferents is considerable smaller in the mouse.

PMID- 11327573
TI  - Effect of aging on the substance P receptor, NK-1, in the spinal cord of rats
      with peripheral nerve injury.
AB  - Substance P (SP) levels in the spinal cords of very old rats are less than the
      levels in younger rats (Bergman et al., 1996). After injury to a peripheral nerve
      in young rats, immunoreactivity (ir) to the SP receptor, NK-1 (neurokinin-1),
      increases in the spinal cord ipsilateral to the injury and the increases are
      correlated with the development of thermal hyperalgesia (Goff et al., 1998). Thus
      we postulated that aged rats might display an increased sensitivity to thermal
      stimulation before peripheral nerve injury and that they might respond
      differently to injury than do younger rats. To test this hypothesis, we used the
      Bennett and Xie model (1988) of chronic constriction injury (CCI) to the sciatic
      nerve to induce a neuropathic pain condition. We investigated the effect of age
      on changes in NK-1 ir in superficial layers of the dorsal horn and on numbers of
      NK ir cells in deeper laminae at the L4-L5 levels of the spinal cord after CCI.
      NK-1 receptors were tagged immunohistochemically and their distribution
      quantified by use of computer-assisted image analysis. NK-1 ir changes were
      related to alterations in thermal and tactile sensitivity that developed after
      CCI in young, mature and aged (4-6, 14-16, and 24-26 months) Fischer F344 BNF1
      hybrid rats. No differences in thermal or tactile sensitivity of young and aged
      rats were seen in the absence of nerve injury. After injury, aged rats developed
      thermal hyperalgesia and tactile allodynia more slowly than did the younger rats.
      NK-1 receptor ir and numbers of NK-1 ir cells in the dorsal horn increased with
      time post-injury in all three groups. NK-1 ir increases were correlated with the
      development of thermal hyperalgesia in those rats that displayed hyperalgesia.
      However, some rats developed an increased threshold to thermal stimuli
      (analgesia) and that also was correlated with increases in NK-1 ir. Thus NK-1 ir
      extent, while correlated with thermal sensitivity in the absence of injury, is
      not a specific marker for disturbances in one particular sensory modality; rather
      it increases with peripheral nerve injury per se.

PMID- 11327574
TI  - Replication and discrimination of limb movement velocity.
AB  - It is well known that proprioception is composed of the senses of movement and
      position. Whereas tests of position sense are quite commonly used, tests of the
      acuity in perception of movement velocity are scarce. In the present study we
      examined some novel tests for assessing the sense of limb movement velocity,
      involving replication and discrimination of single-joint movement velocity.
      Specifically, we investigated: (1) whether replication of limb movement velocity
      is more accurate following active criterion movements as compared to passive; (2)
      whether antagonist muscle contraction during passive limb movement enhances
      velocity discrimination; (3) how criterion movement velocity influences response
      accuracy; (4) the relationship between movement velocity and movement extent
      during velocity replication; and (5) whether subjects really base discrimination
      of velocities on perceived velocity. Sixteen healthy subjects participated in
      four tests (I-IV). For each test, horizontal abductions were performed about the
      right glenohumeral joint from the sagittal plane. The subjects were required to
      actively replicate the velocity of either an active (Test I) or passive (Test II)
      criterion movement, or judge whether a passive/semipassive (passive during
      antagonist muscle contraction) movement was faster or slower than a previous
      passive/semipassive criterion movement (Test III/IV). The results revealed higher
      response accuracy for Test I compared to Test II and for slower movements
      compared to faster, but no difference in response accuracy between Test III and
      IV. For velocity discrimination, the analysis revealed that the subjects based
      their judgment on the difference between criterion and comparison velocity rather
      than time or extent cues.

PMID- 11327575
TI  - Stereocontrolled synthesis of LNA dinucleoside phosphorothioate by the
      oxathiaphospholane approach.
AB  - The application of the oxathiaphospholane approach for the stereocontrolled
      synthesis of LNA dinucleoside phosphorothioate is described. The reaction of ring
      opening condensation proceeds in CH3CN solution in high yield and with over 96%
      stereoselectivity. One of diastereomers of LNA dinucleoside phosphorothioate
      (presumably R(P)) was found to be readily digested by svPDE.

PMID- 11327576
TI  - Peptide synthesis in organic media with subtilisin 72 immobilized on poly(vinyl
      alcohol)-cryogel carrier.
AB  - Serine proteinase subtilisin 72 was covalently attached to the beads of
      poly(vinyl alcohol)-cryogel, a macroporous hydrogel prepared by the freeze-thaw
      technique. The immobilized enzyme was examined as a catalyst in the synthesis of
      protected peptides Z-Ala-Ala-Xaa-Phe-pNA (Xaa = Leu, Glu, Lys) in
      acetonitrile/dimethylformamide mixtures. Immobilized subtilisin catalyzed with
      high yield the formation of peptide bonds between Phe-pNA and acyl donors
      including those with free carboxylic group and non-protected C-terminal basic and
      acidic amino acid residues.

PMID- 11327577
TI  - Heterocycle-based MMP inhibitors with P2' substituents.
AB  - Potent and selective inhibition of matrix metalloproteinases was demonstrated for
      a series of sulfonamide-based hydroxamic acids. The design of the heterocyclic
      sulfonamides incorporates a six- or seven-member central ring with a P2'
      substituent that can be modified. Binding interactions of this substituent at the
      S2' site are believed to contribute to high inhibitory potency against
      stromelysin, collagenase-3 and gelatinases A and B, and to provide selectivity
      against collagenase-1 and matrilysin. An X-ray structure of a stromelysin
      inhibitor complex was obtained to provide insights into the SAR and selectivity
      trends observed for the series.

PMID- 11327579
TI  - Structure determination and comparison of BM567, a sulfonylurea, with terbogrel,
      two compounds with dual action, thromboxane receptor antagonism and thromboxane
      synthase inhibition.
AB  - BM567, a sulfonylurea compound whose crystal structure is here discussed and
      terbogrel, are both thromboxane receptor antagonists and thromboxane synthase
      inhibitors. In this paper, their crystallographic and electronic structures are
      compared and lead to new synthesis prospects among the sulfonylurea series.

PMID- 11327578
TI  - Study of aminoglycoside-nucleic acid interactions by an HPLC method.
AB  - The interactions of a number of aminoglycoside antibiotics with tRNA and DNA were
      studied by an HPLC method. based on tRNA and DNA peak size exclusion. Among the
      compounds studied (deoxystreptamine, neamine, neomycin B, kanamycin A, gentamicin
      A, netilmicin, streptomycin, and the synthetic neamine analogue BKN3), neomycin B
      and the synthetic analogue of neamine were proved to be the most potent binders.

PMID- 11327580
TI  - 3,4-Dihydro-1-isoquinolinamines: a novel class of nitric oxide synthase
      inhibitors with a range of isoform selectivity and potency.
AB  - 3-Phenyl-3.4-dihydro-1-isoquinolinamine is a weak inhibitor of iNOS and nNOS.
      Structural variation of 5a results in inhibitors with a range of potency and
      selectivity for the NOS enzymes, including a potent and very selective iNOS
      inhibitor 5j.

PMID- 11327581
TI  - Thienopyridines: nitric oxide synthase inhibitors with potent in vivo activity.
AB  - 5-Substituted 7-amino-4,5-tetrahydrothieno[2,3-c]pyridines and 6-substituted 4
      amino-6,7-dihydrothieno[3,2-c]pyridines were shown to be exceptionally potent
      inhibitors of inducible and neuronal nitric oxide synthase. Selectivity and
      potency could be modulated by variation of the 5- or 6-substituent. Compound 3e
      showed potent in vivo inhibition of iNOS.

PMID- 11327582
TI  - 2-Acylimino-3H-thiazoline derivatives: a novel template for platelet GPIIb/IIIa
      receptor antagonists.
AB  - In the course of our research for the low-molecular weight RGD peptide mimics, we
      have found that a rigid 2-acylimino-3H-thiazoline structure is suitable for the
      peptide backbone mimics. Introduction of amidinophenyl and beta-alanine moiety as
      arginine and aspartic acid side-chain surrogates to this backbone mimic resulted
      in a highly potent fibrinogen receptor antagonist 2-(4-amidinobenzoylimino)-3,4
      dimethyl-N-(2-carboxyethyl)-3H-thiazoline-5-carboxamide (7c), namely PS-028 (Ki =
      46.5 +/- 5.8 microM).

PMID- 11327583
TI  - 7,8-Dihydropterin-6-carboxylic acid as light emitter of luminous millipede,
      Luminodesmus sequoiae.
AB  - A luminous millipede. Luminodesmus sequoiae, emits light centered at a wavelength
      of 500 nm. To determine the light emitter of this bioluminescent system,
      fluorescent compounds were isolated from pulverized cuticles. NMR and MS spectra
      of these compounds showed them to be pterin derivatives. Furthermore,
      proton/deuterium (H/D) exchange experiments by ESI-Q-TOF-MS and -MS/MS
      measurements have proved to be a powerful tool for elucidating these
      heteroaromatic compounds. Finally, we have concluded that 7,8-dihydropterin-6
      carboxylic acid, a new natural product, is the light emitter of Luminodesmus
      bioluminescence.

PMID- 11327584
TI  - The discovery of RFI-641 as a potent and selective inhibitor of the respiratory
      syncytial virus.
AB  - The design and synthesis of a new potent and selective inhibitor of the
      respiratory syncytial virus are described. This compound, RFI-641, emerged from
      analysis of the structure-activity relationship in a series of biphenyl triazine
      anionic compounds possessing specific anti-RSV activity. The key synthetic step
      involves coupling of diaminobiphenyl 11 with two equivalents of chlorotriazine 10
      under microwave conditions. RFI-641 inhibited RSV in vitro and in vivo models.

PMID- 11327585
TI  - Synthesis and structure-activity studies of side-chain derivatized arylhydantoins
      for investigation as androgen receptor radioligands.
AB  - A series of arylhydantoin derivatives modeled after the antiandrogen RU 58841 was
      generated to identify potential candidates for development as androgen receptor
      (AR) radioligands. Side-chain modified derivatives of RU 58841, suitable for
      labeling with either carbon-11 or radiohalogens (fluorine-18, iodine-123), were
      synthesized and tested for their AR binding affinities. The N-(iodopropenyl)
      derivative 13 (Ki = 13 nM) is a potential candidate for development as a
      radioiodinated AR ligand.

PMID- 11327586
TI  - Thiosugars. Part 9: synthesis and biological evaluation of some 4'-thio-L-arabino
      nucleoside analogues.
AB  - 1-O-Acetyl-2,3,5-tri-O-benzyl-4-thio-L-arabinofuranose (10) was transformed into
      the corresponding cytidine derivative 9 and the adenosine derivative 12. Both
      nucleosides, as well as the previously reported uridine and thymidine analogues 2
      and 3, were tested for their in vitro antiviral activity.

PMID- 11327587
TI  - Synthesis and evaluation of novel amidate prodrugs of PMEA and PMPA.
AB  - Some novel amidate prodrugs of PMEA and PMPA have been synthesised and tested in
      vitro for their biological activity. Compound 5 in particular showed greatly
      enhanced antiviral potency compared with the parent nucleotide analogue. In vitro
      enzymatic studies and structure-activity relationships indicate that the
      degradation mechanism of such prodrugs may be the same as that described for the
      phosphoramidate triesters of nucleotide analogues.

PMID- 11327588
TI  - An improved method for the rapid preparation of 2-amino-4,4a-dihydro-4a,7
      dimethyl-3H-phenoxazine-3-one, a novel antitumor agent.
AB  - A simple and rapid preparation method for a novel antitumor agent, 2-amino-4,4a
      dihydro-4a,7-dimethyl-3H-phenoxazine-3-one (Phx) was described. The procedure
      included (1) the reaction of bovine hemolysates with 2-amino-5-methylphenol, (2)
      one-shot denaturation of hemoglobin and proteins by methanol, and removal of the
      denatured hemoglobin and proteins, (3) concentration of the reaction products,
      and (4) purification by a Sephadex column. These procedures yielded Phx in 34%
      yield.

PMID- 11327590
TI  - Novel, lipophilic derivatives of 2,5-dideoxy-2,5-imino-D-mannitol (DMDP) are
      powerful beta-glucosidase inhibitors.
AB  - Novel derivatives of the D-glucosidase inhibitor 2,5-dideoxy-2,5-imino-D-mannitol
      bearing lipophilic aliphatic or aromatic amides attached to C-1 have been found
      to inhibit beta-glucosidase from Agrobacterium sp. in the nanomolar range. One of
      them, a coumarin derivative, ranks amongst the most active compounds in the class
      of reversible glycosidase inhibitors of the iminoalditol type.

PMID- 11327589
TI  - In vitro metabolism considerations, including activity testing of metabolites, in
      the discovery and selection of the COX-2 inhibitor etoricoxib (MK-0663).
AB  - Characterization of the metabolites of the COX-2 inhibitor etoricoxib (MK-0663
      and L-791,456) produced in vitro indicate formation of an N-oxide pyridine and
      hydroxymethyl pyridine that can further be glucuronidated or oxidized to an acid.
      Significant turnover is observed in human hepatocytes. Several CYPs are involved
      in the oxidative biotranformations and, from in vitro studies, etoricoxib is not
      a potent CYP3A4 inducer or inhibitor. Based on an in vitro whole blood assay,
      none of the metabolites of etoricoxib inhibits COX-1 or contributes significantly
      to the inhibition of COX-2.

PMID- 11327591
TI  - Design, synthesis and stability of N-acyloxymethyl- and N-aminocarbonyloxymethyl
      2-azetidinones as human leukocyte elastase inhibitors.
AB  - A series of N-acyloxymethyl- and N-aminocarbonyloxymethyl derivatives of 2
      azetidinones, 3, with different substituent patterns at the beta-lactam C-3 and C
      4 positions, were designed as potential mechanism-based inhibitors for human
      leukocyte elastase and found to exhibit inhibitory potency and selectivity for
      the enzyme.

PMID- 11327592
TI  - 1,2,5-Thiadiazole derivatives are potent and selective ligands at human 5-HT1A
      receptors.
AB  - Amino acid derivatives of 1,2,5-thiadiazol-3-yl-piperazine related to (+)-WAY
      100135 and WAY-100635 are potent 5-HT1A receptor agonists and antagonists, which
      have selective affinity for 5-HT1A receptors versus alpha1 and dopamine (D2, D3,
      and D4) receptors.

PMID- 11327593
TI  - 2-(3,5-Dimethylphenyl)tryptamine derivatives that bind to the GnRH receptor.
AB  - A series of 2-(3,5-dimethylphenyl)tryptamine derivatives was prepared and
      evaluated on a rat gonadotropin releasing hormone receptor assay. Some para
      substituents on the 4-phenylbutyl side chain attached to the tryptamine nitrogen
      led to compounds with potent GnRH receptor binding. The study has helped define
      structural requirements for GnRH receptor binding for the 2-aryltryptamine GnRH
      antagonists.

PMID- 11327594
TI  - Heterocyclic derivatives of 2-(3,5-dimethylphenyl)tryptamine as GnRH receptor
      antagonists.
AB  - A series of heterocyclic 2-(3,5-dimethylphenyl)tryptamine derivatives was
      prepared and evaluated on a rat gonadotropin releasing hormone receptor assay.
      The carbon tether length and heterocyclic ring attached to the amino group of 2
      (3,5-dimethylphenyl)tryptamine were varied. Several of these derivatives were
      potent GnRH antagonists with the most potent compound having an IC50 of 16 nM.

PMID- 11327595
TI  - Synthesis and structure-activity relationships of guanine analogues as
      phosphodiesterase 7 (PDE7) inhibitors.
AB  - The synthesis of a novel series of guanine analogues is reported. The compounds
      have been assessed in vitro and some analogues have been found to be inhibitors
      of phosphodiesterase type 7 (PDE7).

PMID- 11327596
TI  - Dimeric L-dopa derivatives as potential prodrugs.
AB  - A series of dimeric derivatives (+)-1, and (+)-2, and (+)-3a-d of L-Dopa diacetyl
      esters was synthesized and evaluated as potential L-Dopa prodrugs with improved
      physicochemical properties. All the new compounds showed chemical stability in
      aqueous buffer solutions (pH 1.3 and 7.4). A relatively slow release of L-Dopa in
      human plasma was observed.

PMID- 11327597
TI  - Solution-Phase parallel synthesis of 5-carboxamido 1-benzyl-3-(3
      dimethylaminopropyloxy)-1H-pyrazoles as activators of soluble guanylate cyclase
      with improved oral bioavailability.
AB  - A lipophilicity constrained library of 5-carboxamido 1-benzyl-3-(3
      dimethylaminopropyloxy)-1H-pyrazoles was prepared by solution-phase parallel
      synthesis with removal of acidic by-products using the strongly basic MP
      carbonate resin. Compounds show both activation of soluble guanylate cyclase and
      inhibition of platelet aggregation. Compound 12 also shows 22% oral
      bioavailability in rats.

PMID- 11327598
TI  - Antitumour benzothiazoles. Part 15: The synthesis and physico-chemical properties
      of 2-(4-aminophenyl)benzothiazole sulfamate salt derivatives.
AB  - A series of sulfamate salt derivatives of the potent and selective 2-(4
      aminophenyl)benzothiazole antitumour agents has been prepared and their
      evaluation as potential prodrugs for parenteral administration carried out. The
      salts were sparingly soluble under aqueous conditions (pH 4-9), and degradation
      to the active free amine was shown to occur under strongly acidic conditions. The
      salts were found to be markedly less active than their parent amines against
      sensitive human tumour cell lines in vitro.

PMID- 11327599
TI  - Rational design, synthesis, and biological evaluation of rigid pyrrolidone
      analogues as potential inhibitors of prostate cancer cell growth.
AB  - In view of its role in tumor promotion and signal transduction, protein kinase C
      (PKC) has proven to be an exciting target for cancer therapy. With the aid of
      molecular modeling, we rationally designed and stereoselectively synthesized a
      new class of rigidified pyrrolidone-based PKC activators. Pyrrolidone 15 was
      found to exhibit reasonable affinity for PKCdelta, with lower affinity for the
      other isozymes tested. Pyrrolidone 2 causes the dose-dependent induction of
      apoptosis in LNCaP prostate cancer cells. This apoptotic effect could be markedly
      potentiated by the use of LNCaP cells overexpressing the PKCalpha or delta
      isozymes.

PMID- 11327600
TI  - Ester and hydroxamate analogues of methionyl and isoleucyl adenylates as
      inhibitors of methionyl-tRNA and isoleucyl-tRNA synthetases.
AB  - The structure activity relationship on a series of ester and hydroxamate
      analogues of methionyl and isoleucyl adenylate has been investigated through
      introducing linkers between the 1'-position of ribose and adenine surrogates as
      methionyl-tRNA, and isoleucyl-tRNA synthetase inhibitors, respectively. The
      results indicate that ester analogue 23 was found to be a potent inhibitor of
      Escherichia coli methionyl-tRNA synthetase, and its interaction with the active
      site was proposed by a molecular modeling study.

PMID- 11327601
TI  - Vanilloid and isovanilloid analogues as inhibitors of methionyl-tRNA and
      isoleucyl-tRNA synthetases.
AB  - As aminoacyl adenylate surrogates, a series of methionyl and isoleucyl phenolic
      analogues containing bioisosteric linkers mimicking ribose have been
      investigated. Inhibition of synthesized compounds to the aminoacylation reaction
      by the corresponding Escherichia coli methionyl-tRNA and isoleucyl-tRNA
      synthetases indicated that 18 was found to be a potent inhibitor of isoleucyl
      tRNA synthetase. A molecular modeling study demonstrated that in 18, isovanillate
      and hydroxamate served as proper surrogates for adenine and ribose in isoleucyl
      adenylate, respectively.

PMID- 11327602
TI  - Novel 5,5-disubstitutedpyrimidine-2,4,6-triones as selective MMP inhibitors.
AB  - The 5,5-disubstitutedpyrimidine-2,4,6-triones represent a new class of MMP
      inhibitors showing selectivity for the gelatinases A and B, collagenase-3, and
      human neutrophil collagenase. The SAR presented here is in good agreement with an
      X-ray structure of compound 5 bound to the catalytic domain of stromelysin-1.
      While of the barbiturate structural class, compound 5 did not show any toxic or
      sedative effects.

PMID- 11327603
TI  - Discovery and SAR of diarylsulfide cyclopropylamide LFA-1/ICAM-1 interaction
      antagonists.
AB  - Diarylsulfide cyclopropylamides were synthesized and evaluated as LFA-1/ICAM-1
      interaction antagonists. A substituent pattern was identified which maximized
      potency and minimized protein binding as exemplified by antagonist 30 (IC50 = 5
      nM).

PMID- 11327604
TI  - Novel inhibitors of Leishmanial dihydrofolate reductase.
AB  - The program DOCK3.5 was used to search the Cambridge Structural Database for
      novel inhibitors of Leishmanial dihydrofolate reductase. A number of compounds
      were obtained and screened against the enzyme and against the intact parasite
      Leishmania donovani and the related organisms Trypanosoma brucei and Trypanosoma
      cruzi. The compounds screened showed weak activity in both the enzyme assays and
      the in vitro assays.

PMID- 11327605
TI  - New oxadiazolidinedione derivatives as potent and selective human beta3 agonists.
AB  - As part of our investigation into the development of potent and selective human
      beta3 agonists, a series of thiazolidinedione analogues was prepared and
      evaluated for their biological activity on the human beta3-adrenergic receptor.
      The oxadiazolidinedione derivative 17 was found to be the most potent and
      selective compound in this study, with an EC50 value of 0.02 microM at the beta3
      receptor, 259-fold selectivity over the beta1 receptor, and 745-fold selectivity
      over the beta2 receptor.

PMID- 11327606
TI  - New triterpenes, myrrhanol A and myrrhanone A, from guggul-gum resins, and their
      potent anti-inflammatory effect on adjuvant-induced air-pouch granuloma of mice.
AB  - Myrrhanol A, a new triterpene isolated from guggul (Balsamodendron or Commiphora
      mukul Hook.)-gum resin, displays a potent anti-inflammatory effect on exudative
      pouch fluid, angiogenesis, and granuloma weights in adjuvant-induced air-pouch
      granuloma of mice. Its effects were more marked than those of hydrocortisone and
      the 50% aqueous methanolic extract of the crude drug. Myrrhanol A is a plausible
      candidate for a potent anti-inflammatory agent.

PMID- 11327607
TI  - Novel non-peptide ligands for the somatostatin sst3 receptor.
AB  - A series of imidazole derivatives has been prepared using high throughput
      parallel synthesis. Several compounds showed high affinity (Ki in 10(-6)-10(-8) M
      range) and selectivity at recombinant human somatostatin receptor subtype 3
      (hsst3).

PMID- 11327609
TI  - Commercial and editorial conflicts in thyroid.

PMID- 11327608
TI  - Allyl and propargyl substituted penam sulfones as versatile intermediates toward
      the syntheses of new beta-lactamase inhibitors.
AB  - Several alkenyl derivatives were prepared using allyl penam sulfone as the key
      intermediate. Isomers of these derivatives having beta configuration at C-6
      showed potent activity against CcrA enzyme. A new method was developed to prepare
      propargyl penam sulfone. The majority of the triazoles prepared by this route
      exhibited good activity against all three representative enzymes used for the
      inhibition assay.

PMID- 11327610
TI  - Effect of altered thyroid status on neurotrophin gene expression during postnatal
      development of the mouse cerebellum.
AB  - Thyroid hormone (TH) plays an important role in brain development. The rodent
      cerebellum has been an excellent model for the study of the molecular mechanisms
      of TH action in brain. However, most studies have utilized the rat rather than
      the mouse. Considering the usefulness of mice with regard to diverse genetic
      models, the study of TH effect on mouse cerebellar development is needed. Thus,
      we examined the effect of perinatal hypothyroidism on the expression of
      neurotrophin-3 (NT-3) and brain-derived neurotrophic factor (BDNF) genes, which
      play critical roles in cerebellar development. Newborn mice were rendered
      hypothyroid by administering methimazole and perchlorate in drinking water to
      their mothers. The growth of hypothyroid mice was retarded, which was reversed by
      daily thyroxine administration. NT-3 and BDNF gene expression was depressed in
      the perinatal hypothyroid cerebellum. Furthermore, the expression of retinoid
      receptor-related orphan nuclear hormone receptor-alpha (RORalpha), an orphan
      nuclear receptor that plays critical roles in Purkinje cell development, was also
      decreased. Morphologically, disappearance of the external granule cell layer was
      retarded and arborization of Purkinje cell dendrite was decreased, events that
      were also observed in hypothyroid rats. These results indicate that the mouse
      cerebellum is comparable to the rat cerebellum as a model for the examination of
      the molecular mechanisms of TH action in brain development.

PMID- 11327611
TI  - Reactivity of thyrotropin receptor autoantibodies with the thyrotropin receptor
      on western blots.
AB  - Affinity purified recombinant human thyrotropin receptor (TSHR) was run on sodium
      dodecyl sulfate (SDS) gels and subjected to a renaturing and blotting procedure.
      Twenty sera from thyrotropin receptor autoantibodies (TRAb)-positive patients
      with a history of hyperthyroidism and 20 sera with high levels of TSH blocking
      activity were analyzed. Four of 20 sera with blocking-type of TRAb (i.e., TSH
      antagonist activity) were able to recognize the mature, fully glycosylated 120-kd
      form of the receptor on blots of gels run under reducing conditions. No sera
      recognized the 100-kd high mannose precursor form of the TSHR. Three of the four
      recognized a 74-kd band and 2 of the 4 recognized a 50-kd band. These bands are
      probably proteolytic cleavage fragments of the mature 120-kd TSHR. In the absence
      of reducing agent the same 4 of 20 sera described above together with a further
      serum sample (i.e., 5/20 in total) reacted with the 120-kd form of the receptor.
      No specific reaction with the TSHR was observed on Western blots with the
      remaining 15 sera with TSH blocking activity, nor with 20 sera from patients with
      a history of hyperthyroidism, nor with sera from 10 healthy blood donors, 10
      Hashimoto sera (negative for TRAb) and 10 systemic lupus erythematosus sera. No
      clear differences were observed in the TRAb positive sera that were reactive and
      nonreactive on Western blots in terms of their ability to inhibit TSH binding or
      to immunoprecipitate 125I-labeled TSHR. Overall, our results indicate that the
      mature 120-kd form of the TSHR that is principally responsible for binding TSH is
      also responsible for binding TRAb (when this binding can be detected). These
      observations together with immunoprecipitation and TSH binding inhibition
      studies, emphasize the close relationship between the receptor's binding sites
      for TSH and TRAb.

PMID- 11327612
TI  - Induction of leptin expression in orbital preadipocyte fibroblasts.
AB  - Graves' ophthalmopathy (GO) is an autoimmune disease characterized by an increase
      in the volume of the orbital fatty/connective tissues and extraocular muscles.
      This volume change is due to expansion of the adipose tissues and to accumulation
      of glycosaminoglycans and edema within the connective tissues of the orbit. We
      have shown previously that a subpopulation of confluent human orbital
      preadipocyte fibroblasts can be induced in vitro to differentiate into cells with
      morphological features of adipocytes and that these cultures express functional
      thyrotropin receptor (TSHR). In order to identify and study these cells further,
      we examined the expression of leptin protein and TSHR and leptin mRNA in these
      cultures. Using immunocytochemistry with objective measurement of
      immunofluorescent staining intensity on digitized microscopic images, we
      determined leptin protein expression to be 6 to 37 times greater in
      differentiated cultures than in control cultures. In addition, we showed that the
      expression of both genes is enhanced in differentiated cultures. We suggest that
      an unknown humoral stimulus, present in Graves' disease, might act to induce the
      differentiation of normal orbital fibroblasts into TSHR-bearing adipocytes. This
      process would be expected to result in expansion of the orbital adipose tissues
      and increased TSHR expression within the orbit.

PMID- 11327613
TI  - Does the autoantibody immunodominant region on thyroid peroxidase include amino
      acid residues 742-771?
AB  - Identification of the thyroid peroxidase (TPO) amino acid residues that comprise
      the autoantibody immunodominant region is an important goal that has proven
      difficult because of the conformational nature of the epitopes involved. Recent
      data suggest that the immunodominant region has been located. Thus, by
      autoantibody recognition of tryptic fragments of native TPO, as well as of
      conformational portions of TPO expressed as cell-free translates, the
      autoantibody immunodominant region appears to include amino acid residues 742
      771, near the C terminus of the ectodomain. To evaluate this deduction, we
      expressed as cell-free translates the full TPO ectodomain, as well as TPO
      truncated after residues 741 and 771. The epitopic integrity of these molecules
      was first confirmed by immunoprecipitation by patient sera containing TPO
      autoantibodies. However, autoantibody recognition could involve a minority of TPO
      autoantibodies with the individual sera, not fulfilling the strict criteria for
      immunodominance. In order to obtain definitive data, we performed
      immunoprecipitations on these TPO variants with four recombinant human monoclonal
      autoantibodies that define the immunodominant region. All four monoclonal
      autoantibodies immunoprecipitated TPO 1-741 to the same extent as they did TPO 1
      771 and the full TPO ectodomain, indicating that the immunodominant region
      comprises (at least in large part) amino acid residues upstream of residue 741.

PMID- 11327614
TI  - Differential regulation of Fas-mediated apoptosis in both thyrocyte and
      lymphocyte cellular compartments correlates with opposite phenotypic
      manifestations of autoimmune thyroid disease.
AB  - Several mechanisms are probably involved in determining the evolution of
      autoimmune thyroid disease (AITD) towards either hypothyroidism and the clinical
      syndrome known as Hashimoto's thyroiditis (HT) or toward hyperthyroidism and the
      symptoms of Graves' disease (GD). To gain further insight into such mechanisms we
      performed an exhaustive comparative analysis of the expression of key molecules
      regulating cell death (Fas, Fas ligand [FasL], Bcl-2) and apoptosis in both
      thyrocytes and thyroid infiltrating lymphocytes (TILs) from patients with either
      GD or HT. GD thyrocytes expressed less Fas/FasL than HT thyrocytes, whereas GD
      TILs had higher levels of Fas/FasL than HT TILs. GD thyrocytes expressed
      increased levels of the antiapoptotic molecule Bcl-2 compared to the low levels
      detected in HT thyrocytes. The opposite pattern was observed in GD (low Bcl-2)
      and HT (high Bcl-2) TILs. The patterns of apoptosis observed were consistent with
      the regulation of Fas, FasL, and Bcl-2 described above. Our findings suggest that
      in GD thyroid the regulation of Fas/FasL/Bcl2 favors apoptosis of infiltrating
      lymphocytes, possibly limiting their autoreactive potential and impairing their
      ability to mediate tissue damage. Moreover, the reduced levels of Fas/FasL and
      increased levels of Bcl-2 should favor thyrocyte survival and favor the thyrocyte
      hypertrophy associated with immunoglobulins stimulating the thyrotropin (TSH)
      receptor. In contrast, the regulation of Fas/FasL/Bcl2 expression in HT promotes
      thyrocyte apoptosis, tissue damage, and a gradual reduction in thyrocyte numbers
      leading to hypothyroidism. These findings help define key molecular mechanisms
      contributing to the clinical outcome of thyroid autoimmunity.

PMID- 11327615
TI  - The nature of apoptosis in the thyroid and the role it may play in autoimmune
      thyroid disease.

PMID- 11327616
TI  - One-year prophylactic treatment of euthyroid Hashimoto's thyroiditis patients
      with levothyroxine: is there a benefit?
AB  - Studies in animal models of spontaneous Hashimoto's autoimmune thyroiditis (HT)
      show that prophylactic treatment with levothyroxine (LT4) can reduce incidence
      and degree of lymphocytic infiltration in HT. The aim of the present study was to
      clarify whether there is a benefit of prophylactic treatment with LT4 in patients
      with euthyroid HT with respect to the progression of the autoimmune process.
      Twenty-one patients with euthyroid HT were checked for thyroid function
      (thyrotropin [TSH], free triiodothyronine [FT3], free thyroxine [FT4]), thyroid
      volume, antibodies (thyroglobulin [Tg-Ab], thyroid peroxidase [TPO-Ab]), and
      lymphocyte subsets. Peripheral (PBL) and thyroid-derived lymphocytes (TL) were
      analyzed by triple color flow cytometry. One-half of the patients with euthyroid
      HT were treated with LT4 for 1 year (n = 10). The other half (n = 11) were never
      treated with LT4. TL were obtained by fine-needle aspiration biopsy (FNAB).
      Thirteen healthy subjects (C) without medical history of thyroid disease served
      as controls concerning PBL, and patients with non-toxic nodular goiter (NG; n =
      10) served as controls concerning TL. Thyroid-derived T-helper cells were found
      more frequently in euthyroid patients with HT compared to patients with NG (p <
      0.01). After 1 year of therapy with LT4, TPO-Abs and B lymphocytes decreased
      significantly only in the treated group of euthyroid patients with HT (p < 0.05).
      In contrast, TPO-Abs levels did not change or even increased in untreated
      euthyroid patients with HT. Thyroid volume did not differ before and after
      therapy. Prophylactic treatment of euthyroid patients with HT reduced both
      serological and cellular markers of autoimmune thyroiditis. Therefore,
      prophylactic LT4 treatment might be useful to stop the progression or even
      manifestation of the disease. However, the long-term clinical benefit of
      prophylactic LT4 therapy in euthyroid patients with HT is yet to be established.

PMID- 11327617
TI  - Suppressive levothyroxine therapy has no significant influence on bone
      degradation in women with thyroid carcinoma: a comparison with other disorders
      affecting bone metabolism.
AB  - The aim of this study was to examine different influences on bone degradation
      (estrogen status, thyroid function, parathyroid function, bone metastases) with
      special interest focusing on the significance of suppressive levothyroxine
      therapy (LT4) on bone degradation in patients with differentiated thyroid
      carcinoma (DTC). Two markers of bone degradation (ELItest NTx = U-NTx; Serum
      CrossLaps = S-CTx) were used (1) to quantify the influence of different metabolic
      influences on bone degradation and (2) to compare these two markers with each
      other. One hundred forty samples of 98 female patients ages 23-86 years were
      analyzed. The correlation between the two assays of bone degradation was high (r
      = 0.825; p < 0.001). Both assays demonstrated that estrogen deficiency,
      hyperparathyroidism, and bone metastases caused significant increases of bone
      degradation. A suppressive LT4 therapy, as used for patients with DTC, led to no
      significant increases of S-CTx and U-NTx. The study indicates that a well
      controlled suppressive LT4 therapy has only a minor effect on the degree of bone
      degradation and that a possible estrogen deficiency in patients with DTC has a
      greater impact on bone degradation. Thus, female patients with DTC on suppressive
      LT4 therapy and estrogen deficiency may benefit from hormone replacement therapy,
      as patients with DTC and normal estrogen levels presented similar results to
      euthyroid controls.

PMID- 11327618
TI  - Comparison of some different methods for analysis of thyroid autoantibodies:
      importance of thyroglobulin autoantibodies.
AB  - Blood samples from 141 children and adolescents were used to evaluate differences
      between commercial kits and radioimmunoassay (RIA) methods for detecting thyroid
      autoantibodies. Thyroglobulin autoantibodies (Tg-Ab) were analyzed with a
      hemagglutination kit and a RIA; thyroid peroxidase autoantibodies (TPO-Ab) were
      measured with a gelagglutination assay and a RIA. The results of the antibody
      tests were compared with thyroid function tests (triiodothyronine [T3], thyroxine
      [T4], thyrotropin [TSH]) and with the results of ultrasound of the thyroid in
      antibody-positive patients. The correlation of antibody levels between the two
      methods was higher for TPO-Ab than for Tg-Ab. Moderate to high levels of TPO-Ab
      correlated to elevated TSH levels. Autoimmune thyroiditis (AIT) was found in 6 of
      the 141 children. The RIA-based thyroglobulin assay was the only test that
      identified autoantibodies in all 6 cases. In contrast, the hemagglutination kit
      thyroglobulin assay failed to identify 4 of the 6 AIT cases.

PMID- 11327619
TI  - Thyroid cytology and the risk of malignancy in thyroid nodules: importance of
      nuclear atypia in indeterminate specimens.
AB  - Fine needle aspiration (FNA) cytology is the best test for malignancy in thyroid
      nodules. However, cytologic interpretation of FNA specimens is often difficult,
      especially in the presence of indeterminate microfollicular cytologic patterns,
      which are thought to suggest follicular neoplasm (adenoma or carcinoma). To
      assess the risk of malignancy associated with specific cytologic patterns, we
      correlated preoperative FNA cytologic patterns (n = 484 reports including repeat
      aspirations) with final histological diagnoses for 368 surgical thyroid specimens
      obtained during the period 1994-1998. The overall prevalence of malignancy in the
      surgical specimens was 31% (113 cancers, including 96 papillary and 9 follicular
      carcinomas). For nodules with benign FNA cytologic diagnoses of nodular goiter
      and chronic thyroiditis there was a low risk of malignancy (6/99, or 6.1%).
      Nodules with indeterminate cytologic patterns in the absence of nuclear atypia
      (i.e., microfollicles without nuclear atypia) had a similarly low malignancy risk
      (3/46, or 6.5%). In contrast, 31/52 nodules with cytologic nuclear atypia
      consistent with follicular neoplasm were malignant (60%), including specimens
      with or without microfollicular cytology. Nodules with frankly malignant
      cytologic patterns were almost invariably cancer (54/55), and cytologic diagnoses
      of papillary carcinoma were confirmed at surgery in all 49 cases. These results
      indicate that indeterminate microfollicular cytologic patterns in the absence of
      nuclear atypia are associated with a low risk of malignancy, at least in this
      series. This finding suggests that many nodules with such microfollicular
      cytology might be managed conservatively with observation. In contrast, cytologic
      nuclear atypia consistent with a follicular neoplasm confers a high risk of
      cancer. In addition, frankly malignant cytologic diagnoses, especially papillary
      carcinoma, are highly reliable, and thus may be used as a guide for planning
      surgery appropriate for thyroid cancer.

PMID- 11327620
TI  - Cavernous hemangioma of the thyroid.
AB  - Most current vascular alterations of the thyroid are connected with the
      organization of a thyroid hematoma after fine-needle aspiration (FNA). Cavernous
      hemangioma is a benign congenital vascular malformation that occasionally affects
      the thyroid. This article presents two cases of this rare thyroid pathology
      unrelated to FNA.

PMID- 11327621
TI  - A pituitary tumor in a patient with thyroid hormone resistance: a diagnostic
      dilemma.
AB  - Resistance to thyroid hormone (RTH) is due to mutations in the beta-isoform of
      the thyroid hormone receptor (TR-beta). RTH patients display inappropriate
      secretion of thyrotropin-releasing hormone (TRH) from the hypothalamus and
      thyrotropin (TSH) from the anterior pituitary, despite elevated levels of thyroid
      hormone thyroxine (T4) and triiodothyronine (T3). Thyrotropin-secreting tumors
      are presumed to represent clonal expansion of abnormal cells. Because the
      diagnosis of TSH-secreting tumors tends to be delayed and curative surgical
      resection remains under 50%, early diagnosis is paramount. Current diagnostic
      strategies suggest that RTH patients are distinguishable from patients with TSH
      secreting pituitary tumors by the use of standard laboratory tests and imaging.
      Here, we present a woman in whom the standard evaluation for inappropriate TSH
      secretion was insufficient to distinguish these entities. The patient had a low
      normal TRH stimulation test and an unmeasurable alpha-glycoprotein subunit level;
      however, a pituitary magnetic resonance imaging (MRI) revealed an adenoma. More
      testing using a T3 suppression test supported a RTH diagnosis and a R438H
      mutation was found in the TR-beta gene. To our knowledge, this represents the
      first report of an apparently incidental pituitary adenoma in the setting of
      documented resistance to thyroid hormone. As such, it raises the question of
      whether RTH predisposes to pituitary hyperplasia and adenoma development.

PMID- 11327622
TI  - Thyroid hemilobar atrophy in patients diagnosed as having Hashimoto's
      thyroiditis.

PMID- 11327623
TI  - Low dose perchlorate (3 mg daily) and thyroid function.

PMID- 11327624
TI  - Insulin-mediated sympathetic stimulation: role in the pathogenesis of obesity
      related hypertension (or, how insulin affects blood pressure, and why).
AB  - Thus, the evidence summarized here supports an important role for insulin and the
      sympathetic nervous system in the pathogenesis of obesity-related hypertension.
      Is it possible that insulin-mediated sympathetic stimulation contributes a pro
      hypertensive effect in non-obese as well? It seems possible in young borderline
      hypertensives where sympathetically mediated thermogenic mechanisms are potent
      enough to compensate for the increased caloric intake, thereby enabling these
      young hypertensives to avoid obesity. This is consistent with an observation made
      in the original Framingham cohort that not only did obesity predict the eventual
      development of hypertension, but hypertension, as well, predicted the eventual
      development of obesity. A reasonable interpretation of these data suggests that
      as subjects age and the effectiveness of thermogenic mechanisms wanes, obesity
      might develop as a consequence of increased caloric intake no longer effectively
      buffered by the increased SNS activity. It is important to note that the
      mechanisms described here exert a pro-hypertensive effect and cannot properly be
      considered to 'cause' hypertension. Hypertension is rarely the consequence of a
      single mechanism. It is also true, as pointed out convincingly by Julius and his
      colleagues, that enhanced sympathetic activity, as a primary factor, can be
      associated with both hypertension, insulin resistance and, possibly, obesity
      [39]. And, finally, it should be noted that the mechanism described here is not
      the only mechanism linking obesity and hypertension. A rapidly emerging body of
      evidence indicates that leptin, the polypeptide product of the ob/ob gene
      secreted from adipose tissue, exerts potent central neural effects on both
      appetite and sympathetic activity. Leptin levels, elevated in obese humans, have
      the potential to increase both sympathetic activity and blood pressure [40-43]. A
      more comprehensive summary of the relationships between hypertension and obesity
      may, therefore, involve insulin and leptin, as well as the SNS, as represented in
      the schema presented in Figure 7. Both leptin and insulin may, therefore, be
      considered as compensatory mechanisms recruited to restore energy balance, with
      the SNS as one of the effector arms. Viewed in this way, obesity-related
      hypertension is inextricably linked to the metabolic economy of the obese.

PMID- 11327625
TI  - The relation of oxidative DNA damage to hypertension and other cardiovascular
      risk factors in Tanzania.
AB  - OBJECTIVES: To clarify the mechanism of involvement of oxidative stress in
      hypertensives, we investigated the relationship between the marker of oxidative
      DNA damage, urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), and cardiovascular risk
      factors, such as hypertension and serum glycosylated hemoglobin (HbA1c), among
      Tanzanians aged 46-58 years who were not on antihypertensive medication. DESIGN
      AND METHODS: Sixty subjects (males/females, 28/ 32) were selected randomly from
      the subjects who completed a 24h urine collection in our epidemiological study at
      Dar es Salaam, Tanzania in 1998. The subjects were divided into two groups,
      hypertensive subjects (systolic blood pressure (SBP) > or = 140 mmHg and/or
      diastolic blood pressure (DBP) > or =90 mmHg) and normotensive subjects (SBP <
      140 mmHg and DBP < 90 mmHg) or hyperglycemic subjects (HbA1c > or = 6.0%) and
      normoglycemic subjects (HbA1c < 6.0%). Biological markers from urine and blood
      were analyzed centrally in the WHO Collaborating Center. RESULTS: The mean levels
      of HbA1c and 8-OHdG were significantly higher in the hypertensive subjects than
      in the normotensive subjects (P < 0.05). Urinary 8-OHdG was significantly higher
      in hyperglycemic subjects than in normoglycemic subjects. HbA1c was positively
      correlated with the 24-h urinary 8-OHdG excretions (r= 0.698, P < 0.0001).
      CONCLUSIONS: These findings suggest oxidative DNA damage is increased in
      hypertensive subjects, and there is a positive correlation between the level of
      blood glucose estimated as HbA1c and oxidative DNA damage. Hyperglycemia related
      to insulin resistance in hypertension in Tanzania is associated with increased
      urinary 8-OHdG.

PMID- 11327626
TI  - Different associations of blood pressure with 24-hour urinary sodium excretion
      among pre- and post-menopausal women. WHO Cardiovascular Diseases and Alimentary
      Comparison (WHO-CARDIAC) Study.
AB  - OBJECTIVE: Having found no definite relationship between blood pressure (BP) and
      24h sodium excretion in women aged 48-56 years (in contrast to the results in men
      of the same age) in the WHO Cardiovascular Diseases and Alimentary Comparison
      (WHO-CARDIAC) Study, we analyzed the data to investigate whether the sodium-BP
      association differed between pre- and post-menopausal women. DESIGN AND METHODS:
      The WHO-CARDIAC is a multicenter cross-sectional study, involving, as of July
      2000, 60 collaborating centers in 25 countries. In each center, 100 men and 100
      women aged 48-56 years were selected randomly from the general population of the
      area. In this report, 2,212 women in 21 centers located in 17 countries
      worldwide, who had data on menopausal status, were studied. RESULTS: After
      adjustment for age, body mass index (BMI) and 24h urinary potassium excretion,
      24h sodium excretion was positively and significantly associated with systolic
      blood pressure (SBP) [pooled regression coefficient: 0.037 (SE 0.01), P < 0.01]
      and with diastolic blood pressure (DBP) [0.023 (0.006), P< 0.01] in post
      menopausal women. Pooled regression coefficients of sodium-BP association were
      not significant in pre-menopausal women (P< 0.05). Cross-center correlation
      analyses of the 21 centers showed that 24h sodium excretion was positively
      associated with SBP and DBP in both pre- and post-menopausal women, and this
      positive association between sodium excretion and SBP was significant in post
      menopausal women (R2 = 0.23, P = 0.029). CONCLUSION: Different associations
      between sodium and BP were observed in women with pre- and post-menopausal
      status. There may be a tendency for salt sensitivity to increase at the
      menopause.

PMID- 11327627
TI  - Relevance of endothelium-derived hyperpolarizing factor in the effects of
      hypertension on rat coronary relaxations.
AB  - OBJECTIVES: To evaluate the relative participation of nitric oxide (NO),
      endothelium-derived hyperpolarizing factor (EDHF) and prostanoids in the relaxing
      responses induced by acetylcholine and isoproterenol in isolated coronary
      arteries from adult Wistar- Kyoto (WKY) rats and spontaneously hypertensive rats
      (SHR). DESIGN AND METHODS: Male adult WKY rats and SHR were used in the study.
      Segments from left coronary arteries (approximately 350-380 microm internal
      diameter and 2 mm long) were mounted in an isometric myograph and pre-contracted
      with serotonin. Dose-response curves to acetylcholine and isoproterenol were
      carried out in absence and presence of the NO synthesis inhibitor NG-nitro-L
      arginine methyl ester (LNAME), the inhibitor of the cyclo-oxygenase, indomethacin
      and KCI. Areas under the respective dose-response curves were used to calculate
      the approximate relative participation of NO, EDHF and prostanoids. RESULTS:
      Relaxations to either acetylcholine or isoproterenol were lower in SHR than in
      WKY rats. In WKY rats, presence of LNAME diminished (P< 0.05) relaxation to
      acetylcholine from 10(-9) to 10(-6) mol/l, and induced a contracting response at
      10(-5) and 10(-4) mol/l of acetylcholine. Addition of indomethacin did not
      significantly affect dose-related relaxation to acetylcholine 10(-9) to 10(-6)
      mol/l in WKY rats, and reduced (P < 0.05) the contracting response observed at
      10(-5) mol/l of acetylcholine. In SHR, addition of LNAME markedly reduced (P<
      0.05) acetylcholine relaxations, but did not produce any contracting effect.
      Addition of indomethacin on top of LNAME slightly (P< 0.05) enhanced relaxing
      response to acetylcholine in SHR. Presence of LNAME in the media diminished (P <
      0.05) relaxation to isoproterenol in both WKY rats and SHR. Addition of
      indomethacin on top of LNAME increased (P< 0.05) isoproterenol-relaxing response
      to levels similar to and higher than control conditions in WKY rats and SHR,
      respectively. Addition of KCI blunted both acetylcholine- and isoproterenol
      relaxations in both groups. CONCLUSIONS: NO and EDHF are the main endothelium
      derived relaxing factors underlying acetylcholine and isoproterenol relaxations
      in rat coronary arteries, respectively. EDHF reduction, and not only NO reduction
      play a key role in the diminished coronary relaxations induced by acetylcholine
      and isoproterenol in SHR. An arachidonic acid derivative with contracting
      activity released by acetylcholine and isoproterenol in a differential manner,
      could oppose the relaxing actions of NO and EDHF.

PMID- 11327628
TI  - Effect of acute blood pressure reduction on endothelial function in the brachial
      artery of patients with essential hypertension.
AB  - OBJECTIVES: To evaluate the effect of acute blood pressure reduction on
      endothelium-dependent vasodilation in the peripheral circulation of essential
      hypertensive patients. DESIGN: A parallel group study; endothelial function
      measured in 64 essential hypertensive patients before and after (2 h) treatment
      with nifedipine (20 mg, n = 32) or captopril (50 mg, n = 32), p.o., randomly
      assigned. METHODS: In hypertensive patients, we evaluated flow-mediated,
      endothelium-dependent dilation (FMD, high resolution ultrasound) of the brachial
      artery compared with endothelium-independent response to glyceryl trinitrate
      (GTN, 25 microg s.l.). Automatic computerized analysis was used to measure
      brachial artery diameter on end-diastolic frames acquired every second during the
      study. Sixty-six healthy normotensive subjects were also evaluated to assess the
      presence of endothelial dysfunction in hypertensive patients. RESULTS:
      Hypertensive patients showed a significantly (P< 0.01) lower FMD (5.9 +/- 2.5%)
      as compared to healthy controls (7.7 +/- 3.8%). The response to GTN was similar
      in normotensive subjects (7.5 +/- 3.1%) and hypertensive patients (7.2 +/- 6.5%).
      At baseline brachial artery diameter, FMD and response to GTN were similar in the
      nifedipine- and captopril-treated groups. Nifedipine and captopril similarly
      reduced blood pressure, but only nifedipine increased heart rate. Acute
      nifedipine, but not captopril, significantly (P< 0.01) increased brachial artery
      diameter, while FMD and response to GTN were not modified after nifedipine or
      captopril. CONCLUSIONS: Endothelial dysfunction in the brachial artery of
      essential hypertensive patients is not improved by acute blood pressure
      reduction.

PMID- 11327629
TI  - Differential activation of extracellular signal-regulated protein kinase 1/2 and
      p38 mitogen activated-protein kinase by AT1 receptors in vascular smooth muscle
      cells from Wistar-Kyoto rats and spontaneously hypertensive rats.
AB  - OBJECTIVES: The present study investigates effects of angiotensin II on
      activation of extracellular signal-regulated protein kinase (ERK) 1/2, p38
      mitogen activated-protein kinase (p38MAPK) and c-Jun amino terminal kinase (JNK)
      in vascular smooth muscle cells from spontaneously hypertensive rats (SHR).
      METHODS: Vascular smooth muscle cells (VSMC) from mesenteric arteries of Wistar
      Kyoto (WKY) rats and SHR were studied. Angiotensin II-induced phosphorylation of
      ERK1/2, JNK and p38MAPK were assessed by Western blot analysis. c-fos mRNA
      expression by angiotensin II was determined by reverse transcriptase-polymerase
      chain reaction in the absence and presence of PD98059, selective inhibitor of
      ERK1/2-dependent pathways and SB202190, selective p38MAPK inhibitor. RESULTS:
      Angiotensin II increased phosphorylation of ERK1/2 and p38MAPK, but not JNK.
      Responses were significantly increased in SHR compared with WKY. Irbesartan, AT1
      receptor antagonist, but not PD123319, AT2 receptor blocker, abolished
      angiotensin II-induced effects. PP2, selective Src inhibitor, decreased
      angiotensin II-mediated activation of MAP kinases. Angiotensin II increased c-fos
      mRNA expression in SHR and had a small stimulatory effect in WKY. These actions
      were inhibited by PD98059, whereas SB202190 had no effect. CONCLUSIONS:
      Angiotensin II-induced activation of vascular ERK1/2 and p38MAPK is increased in
      SHR. These effects are mediated via AT1 receptors, which activate Src-dependent
      pathways. Overexpression of c-fos mRNA in SHR is due to ERK1/2-dependent, p38MAPK
      independent pathways. Our results suggest that angiotensin II activates numerous
      MAP kinases in VSMCs and that differential activation of these kinases may be
      important in altered growth signaling in VSMCs from SHR.

PMID- 11327630
TI  - The angiotensin II AT1 receptor antagonist irbesartan prevents thromboxane A2
      induced vasoconstriction in the rat hind-limb vascular bed in vivo.
AB  - OBJECTIVE: We studied the vasoconstrictor effects of the thromboxane A2 (TxA2)
      analogue U46619 in the perfused hind limb of rats under constant flow before and
      after intravenous injection of irbesartan, an angiotensin II AT1 receptor
      antagonist, to test whether irbesartan interacts in vivo with the thromboxane
      A2/prostaglandin endoperoxidase H2 (TxA2/PGH2) receptor. DESIGN: Male Sprague
      Dawley rats (n = 15, body weight 350-420 g) were anesthetized with
      thiobutabarbital sodium (Inactin, 100 mg/kg intraperitoneally). Regional vascular
      responses to U46619 (0.5 and 1.0 microg) were investigated in the rat hind
      quarter under conditions of controlled flow before and after administration of
      irbesartan (10 mg/kg, intravenously). In addition, to test the specificity of the
      effect of irbesartan on U46619, phenylephrine (0.5, 1.0 microg) and another AT1
      receptor antagonist, candesartan CV11974 (0.3 mg/kg, intravenously) were used.
      RESULTS: The dose-dependent increases in hind-limb perfusion pressure produced by
      U46619 were significantly attenuated by prior injection of irbesartan, at a dose
      that blocked the angiotensin II (Ang II) pressor responses. The specificity for
      the response was shown with the demonstrations that the increase in vascular
      resistance produced by phenylephrine was unchanged by irbesartan and,
      furthermore, that the increase in vascular resistance produced by U46619 was
      unchanged by another AT1 receptor antagonist, candesartan. CONCLUSION: This study
      demonstrates that irbesartan interacts at the TxA2/PGH2 receptor in the rat's
      hind limb in vivo, to modify changes in local regional vascular resistance. The
      dual antagonistic actions of irbesartan, acting at both AT1 and TxA2 receptors in
      blood vessels, may overall enhance its therapeutic profile in the treatment of
      hypertension.

PMID- 11327631
TI  - Vasoactive diadenosine polyphosphates in human placenta: possible candidates in
      the pathophysiology of pre-eclampsia?
AB  - BACKGROUND: One hypothesis of the pathophysiology of pre-eclampsia is that
      placentally derived, yet unidentified, vasoactive factors are released into the
      maternal circulation, causing hypertension. OBJECTIVE: To determine if
      diadenosine polyphosphates, new potent vasoconstrictors, are present in human
      placenta. METHODS AND RESULTS: Human placental tissue was homogenated and
      fractionated by size-exclusion chromatography, affinity chromatography, anion
      exchange chromatography and reversed-phase chromatography. In fractions purified
      to homogeneity, diadenosine diphosphate, diadenosine triphosphate, diadenosine
      tetraphosphate, diadenosine pentaphosphate, diadenosine hexaphosphate and
      diadenosine heptaphosphate were identified by matrix-assisted laser
      desorption/ionization mass spectrometry, retention-time comparison and enzymatic
      cleavage analysis. CONCLUSIONS: The presence of diadenosine polyphosphates in
      human placenta makes them possible candidates for involvement in the
      pathophysiology of pre-eclampsia. However, their contribution to the
      pathophysiology of eclampsia requires substantiation in further studies.

PMID- 11327632
TI  - The release of the substrate for xanthine oxidase in hypertensive patients was
      suppressed by angiotensin converting enzyme inhibitors and alpha1-blockers.
AB  - OBJECTIVE: Hyperuricemia is associated with the vascular injury of hypertension,
      and purine oxidation may play a pivotal role in this association, but the
      pathophysiology is not fully understood. We tested the hypothesis that in
      hypertensive patients, the excess amount of the purine metabolite, hypoxanthine,
      derived from skeletal muscles, would be oxidized by xanthine oxidase, leading to
      myogenic hyperuricemia as well as to impaired vascular resistance caused by
      oxygen radicals. METHODS: We investigated the production of hypoxanthione, the
      precursor of uric acid and substrate for xanthine oxidase, in hypertensive
      patients and found that skeletal muscles produced hypoxanthine in excess. We used
      the semi-ischemic forearm test to examine the release of hypoxanthine (deltaHX),
      ammonium (deltaAmm) and lactate (deltaLAC) from skeletal muscles in essential
      hypertensive patients before (UHT: n = 88) and after treatment with
      antihypertensive agents (THT: n = 37) in comparison to normotensive subjects (NT:
      n = 14). RESULTS: deltaHX, as well as deltaAmm and deltaLAC, were significantly
      higher in UHT and THT (P< 0.01) than in NT. This release of deltaHX from
      exercising skeletal muscles correlated significantly with the elevation of
      lactate in NT, UHT and THT (y = 0.209 + 0.031x; R2 = 0.222, n = 139: P < 0.01).
      Administration of doxazosin (n = 4), bevantolol (n = 5) and alacepil (n = 8) for
      1 month significantly suppressed the ratio of percentage changes in deltaHX by 
      38.4 +/- 55.3%, -51.3 +/- 47.3% and -76.3 +/- 52.2%, respectively (P< 0.05) but
      losartan (n = 3), atenolol (n = 7) and manidipine (n = 10) did not reduce the
      ratio of changes; on the contrary, they increased it in deltaHX by +188.2 +/-
      331%, +96.2 +/- 192.2% and +42.6 +/- 137.3%, respectively. The elevation of
      deltaHX after exercise correlated significantly with the serum concentration of
      uric acid at rest in untreated hypertensive patients (y = 0.194 - 0.255x; R2 =
      0.185, n = 30: P < 0.05). The prevalence of reduction of both deltaHX and serum
      uric acid was significantly higher in the patients treated with alacepril,
      bevantolol and doxazosin (67%: P < 0.02) than in the patients treated with
      losartan, atenolol and manidipine (12%). CONCLUSIONS: It is concluded that the
      skeletal muscles of hypertensive patients released deltaHX in excess by
      activation of muscle-type adenosine monophosphate (AMP) deaminase, depending on
      the degree of hypoxia. The modification of deltaHX by angiotensin-converting
      enzyme inhibitors and alpha1-blockers influenced the level of serum uric acid,
      suggesting that the skeletal muscles may be an important source of uric acid as
      well as of the substrate of xanthine oxidase in hypertension.

PMID- 11327633
TI  - Subcellular localization of angiotensin II in kidney and adrenal.
AB  - OBJECTIVES: To investigate whether tissue angiotensin II generation occurs intra-
      or extracellularly, we studied the subcellular localization of angiotensin II in
      kidney and adrenal, two organs with high endogenous angiotensin II
      concentrations. DESIGN AND METHODS: Tissues were obtained, following a 1 h
      infusion of 125I-angiotensin I or 125I-angiotensin II to simultaneously determine
      the localization of plasma-derived angiotensin II, from five control pigs and
      four pigs that had been pretreated with the AT1 receptor antagonist eprosartan.
      Subcellular organelles, prepared by differential centrifugation from homogenized
      tissue, were characterized using organelle-specific markers. RESULTS: 125I
      angiotensin II and angiotensin II were present in all organelles, with identical
      distribution profiles. In mitochondria-enriched fractions the relative specific
      activities [RSAs = (concentration per mg protein in fraction)/(concentration per
      mg protein in homogenate)] of the two peptides were similar to those in
      homogenate, whereas in cytosol-enriched fractions their RSAs were five- to 10
      fold lower (P< 0.05 versus homogenate). In microsome- as well as in lysosome
      enriched fractions the RSAs of 125I-angiotensin II and angiotensin II were two-
      to four-fold higher than in homogenate (P < 0.05), and their RSAs were also
      higher in renal nuclei-enriched fractions (P< 0.05). Eprosartan increased plasma
      angiotensin II to a larger degree than tissue angiotensin II and greatly reduced
      tissue 125I-angiotensin II. This led to similar decreases in the tissue/plasma
      concentration ratios of 125I-angiotensin II and angiotensin II. The subcellular
      distribution of both angiotensin II peptides was not affected by eprosartan.
      CONCLUSIONS: Local angiotensin II synthesis in adrenal and kidney occurs
      predominantly extracellularly, and is followed by rapid AT1 receptor-mediated
      endocytosis, thereby leading to high intracellular angiotensin II levels.

PMID- 11327634
TI  - Role of angiotensin II type 1 receptor in the leucocytes and endothelial cells of
      brain microvessels in the pathogenesis of hypertensive cerebral injury.
AB  - OBJECTIVES: To elucidate the mechanisms of activation of polymorphonuclear
      neutrophils (PMNs) and their adhesion to endothelial cells in hypertensive
      cerebral injury, and to determine the effects of angiotensin II type 1 (AT1)
      receptor antagonism on PMNs and endothelial cells. DESIGN: We examined expression
      of AT1 receptor in PMNs in relation to that in endothelial cells of brain
      microvessels, using mature stroke-prone spontaneously hypertensive rats (SHRSP).
      METHODS: To investigate the expression of AT1 receptor, we used 23-week-old male
      spSHRs and age-matched Wistar-Kyoto (WKY) rats. For the effects of AT1 receptor
      blockade, the AT1 receptor antagonist, TCV-116, was orally administered at a
      dosage of 0.5 mg/kg per day for 4 weeks in rats from age 19 weeks. A PMN-rich
      fraction was obtained by density gradient using Ficol-hypaque. AT1 receptor
      expression in PMNs was investigated by immunohistochemistry (avidin-biotinylated
      peroxidase complex method) and reverse transcriptase-polymerase chain reaction
      (RT-PCR). Expression of macrophage-1 (Mac-1) in PMNs was examined by flow
      cytometry. Expression of intercellular adhesion molecule-1, glucose transporter-1
      and fibrinogen in the cerebral cortex (occipital region) was investigated by
      immunohistochemistry. RESULTS: AT1 receptor was identified in PMNs by both
      immunohistochemistry and RT-PCR. It was also detected in the cerebral cortex.
      Expression in both types of cells was much more intense in spSHRs than in WKY
      rats. AT1 receptor antagonism ameliorated the enhanced expression of Mac-1 in
      PMNs. In addition, it was confirmed that enhanced expression of adhesion
      molecules and increased permeability of brain microvessels were decreased by AT1
      receptor antagonism. CONCLUSIONS: The results indicate that both PMNs and brain
      microvessel endothelial cells possess AT1 receptor, that AT1 receptor antagonism
      ameliorates endothelial injury via inhibition of PMNs and endothelial cell
      adhesion, and that angiotensin II must be a key factor in hypertensive
      endothelial injury.

PMID- 11327635
TI  - Adrenomedullin stimulates DNA synthesis of rat adrenal zona glomerulosa cells
      through activation of the mitogen-activated protein kinase-dependent cascade.
AB  - BACKGROUND: Adrenal zona glomerulosa cells are provided with adrenomedullin
      receptors. Adrenomedullin has recently been found to enhance proliferation of
      cultured rat vascular smooth muscle cells and zona glomerulosa cells. OBJECTIVE:
      To investigate whether adrenomedullin affects rat zona glomerulosa proliferative
      activity through the tyrosine kinase and extracellular signal regulated kinases
      (ERKs) pathways. METHODS: Dispersed rat zona glomerulosa cells were cultured in
      vitro for 24 h and then exposed to adrenomedullin (10(-7) mol/l), alone or in the
      presence of tyrphostin-23 (10(-5) mol/l) or PD-98059 (10(-4) mol/l), for 24 or 48
      h. To assess the rate of DNA synthesis, 5-bromo-2'-deoxyuridine (BrdU, 20 mg/ml)
      was also added to the medium and BrdU-positive cells were detected by
      immunocytochemistry. The expression of ERKs and the effect of adrenomedullin on
      ERKs phosphorylation and activity were assayed in dispersed zona glomerulosa
      cells. RESULTS: Adrenomedullin significantly increased the percentage of BrdU
      positive (phase-S) zona glomerulosa cells; this effect was blocked by either the
      tyrosine kinase inhibitor, tyrphostin-23, or the mitogen-activated protein kinase
      kinase (MEK-1) inhibitor, PD-98059. Both zona glomerulosa and zona
      fasciculata/reticularis express ERK-1 (44 kDa) and ERK-2 (42 kDa) isoforms.
      However, adrenomedullin phosphorylated ERK-1 and ERK-2 only in the zona
      glomerulosa; this effect was blunted by the MEK-1 inhibitor, PD98059, and by the
      calcitonin gene-related peptide type 1 (CGRP-1) receptor antagonist, CGRP8-37,
      but not by the adrenomedullin C-terminal fragment, ADM22-52. CONCLUSION:
      Adrenomedullin stimulates the growth of rat zona glomerulosa cells through
      activation of CGRP-1 receptor, linked to the tyrosine kinase-MEK-1-ERKs
      signalling pathway. These results confirm the complex role played by this peptide
      in the regulation of zona glomerulosa cell physiology.

PMID- 11327636
TI  - Hypoxic induction of adrenomedullin in cultured human umbilical vein endothelial
      cells.
AB  - OBJECTIVES: The current study evaluated the hypoxic induction of adrenomedullin
      gene expression and secretion, and its mechanism in cultured human umbilical vein
      endothelial cells (HUVEC). METHODS: HUVEC were exposed to hypoxia or normoxia as
      controls for 1 to 24 h. Using Northern blot analysis and a radioimmunoassay, we
      evaluated adrenomedullin expression in HUVEC. The transcriptional component of
      adrenomedullin gene regulation was assessed by nuclear run-off experiments, and
      adrenomedullin mRNA half-life was measured by actinomycin D experiments. RESULTS:
      We found that hypoxic conditions (1-3% oxygen) significantly increased
      adrenomedullin mRNA and protein in HUVEC. This increase was inversely
      proportional to oxygen tension and was reversible upon re-exposure to a 21%
      oxygen environment Nuclear run-off experiments revealed the enhanced
      transcriptional rate of adrenomedullin gene. Next, actinomycin D experiments
      revealed the enhanced adrenomedullin mRNA stability. CONCLUSIONS: These results
      indicate that hypoxia increases adrenomedullin gene expression and secretion in
      HUVEC by transcriptional and post-transcriptional mechanisms. Hypoxic induction
      of adrenomedullin may play a pathophysiological role in the vascular systems.

PMID- 11327637
TI  - A novel effect of angiotensin on renal sympathetic nerve activity in mice.
AB  - OBJECTIVE: The goals of this study were to characterize the effects of
      angiotensin II (Ang II) on renal sympathetic nerve activity (RSNA) and to define
      mechanisms of its actions in mice. DESIGN: The experiments were performed in
      sodium pentobarbital anesthetized C57BL/6J mice to investigate the effects of
      intravenous administration of Ang II on RSNA recorded from renal sympathetic post
      ganglionic nerve fibers. RESULTS: Intravenous (i.v.) administration of Ang II (4
      ng/g) increased arterial pressure and evoked a biphasic change in RSNA:
      inhibition of high-amplitude phasic bursts of RSNA secondary to the initial rise
      of arterial pressure followed by activation of low-amplitude continuously
      discharging RSNA that exceeded baseline activity (255 +/- 72% baseline, n = 8).
      The peak change of mean arterial pressure (MAP) was +60 +/- 4 mmHg (n = 8). In
      the same group of animals, norepinephrine (40 ng/g) caused an equivalent increase
      in MAP (+57 +/- 5 mmHg) and essentially abolished RSNA. The Ang II-induced
      activation of RSNA was dose-dependent (0.5-4 ng/g, n = 7) and was abolished by
      the Ang II type 1 (AT1) receptor blocker, losartan (10 microg/g, i.v.) (301 +/-
      61 versus 117 +/- 22% baseline, before versus after losartan, n = 5). The
      ganglionic blocker, hexamethonium (30 microg/g, i.v.), eliminated baseline high
      amplitude bursts of RSNA but did not blunt the Ang II-induced RSNA (n = 6). In
      baroreceptor denervated and vagotomized mice, Ang II failed to inhibit high
      amplitude bursts of RSNA but continued to trigger low-amplitude continuous RSNA.
      CONCLUSION: We conclude that Ang II activates renal sympathetic nerves that
      discharge in a continuous pattern, distinctly different than the normal baseline
      high-amplitude bursts of RSNA. The mechanism may involve direct activation of
      post-ganglionic sympathetic neurons mediated through AT1 receptors.

PMID- 11327638
TI  - Atrial natriuretic peptide augments the variability of sympathetic nerve activity
      in human heart failure.
AB  - OBJECTIVES: Activation of the sympathetic nervous system, decreased heart rate
      variability (HRV), and loss of modulation of muscle sympathetic nerve activity
      (MSNA) within the low frequency (LF, 0.05-0.15 Hz) range are three adverse
      features of advanced congestive heart failure (CHF). In healthy men, atrial
      natriuretic peptide (ANP) infusion attenuates reflex increases in MSNA and
      reduces LF components of HRV spectral power. Sympathoinhibitory actions have also
      been documented in CHF, but effects on the variability of MSNA and HRV have not
      been described. DESIGN AND METHODS: Heart rate and MSNA were recorded in 10 men
      (aged 39 +/- 3 years, mean +/- SE) with dilated cardiomyopathy (mean EF 20 +/-
      4%) treated with angiotensin converting enzyme (ACE) inhibitors. Subjects
      received i.v. ANP (50 microg bolus then 50 ng/kg/min) and nitroglycerin (NTG, 8
      mg/min) as a hemodynamic control. Signals at baseline, and 13-20 min into each
      infusion were submitted to spectral analysis. RESULTS: ANP had no effect on HRV,
      but increased MSNA LF (from 7.9 +/- 1.5 to 12.1 +/- 2.6 U2; P< 0.02) and total
      spectral power (from 47.9 +/- 5.4 to 61.9 +/- 6.8 U2; P < 0.05). NTG had no
      effect on the variability of MSNA or HRV. CONCLUSIONS: In CHF patients receiving
      ACE inhibitors, ANP (i) does not suppress HRV and (ii) enhances the modulation of
      MSNA, particularly within the LF range. This latter action is not observed with
      NTG. These findings suggest beneficial actions of exogenous ANP on neurogenic
      circulatory control.

PMID- 11327639
TI  - Neuronal nitric oxide strongly suppresses sympathetic outflow in high-salt Dahl
      rats.
AB  - OBJECTIVE: To investigate the effects of a selective inhibitor of neuronal nitric
      oxide synthase (nNOS), 7-nitroindazole, on peripheral sympathetic outflow in Dahl
      rats. DESIGN AND METHODS: Dahl salt-sensitive and salt-resistant rats were fed
      either a regular-salt (0.4% NaCl) or a high-salt (8% NaCl) diet for 4 weeks. In
      chronically instrumented conscious rats, renal sympathetic nerve activity (RSNA)
      was measured in both baroreceptor-loaded and baroreceptor-unloaded states. The
      baroreceptor unload was performed by decreasing arterial pressure with occlusion
      of the inferior vena cava. RESULTS: 7-Nitroindazole (307 micromol/kg
      intraperitoneally) increased resting RSNA from 24 +/- 3% to 38 +/- 6% with an
      increase in mean arterial pressure of 15 +/- 3 mmHg, and increased baroreceptor
      unloaded RSNA from 100% to 278 +/- 16% in salt-sensitive Dahl rats receiving a
      high-salt diet However, 7-nitroindazole did not increase resting RSNA, but did
      increase baroreceptor-unloaded RSNA from 100% to 179 +/- 15%, 177 +/- 15%, and
      133 +/- 4% in salt-sensitive Dahl rats receiving a regular-salt diet, salt
      resistant Dahl rats receiving a high-salt diet, and salt-resistant Dahl rats
      receiving a regular-salt diet, respectively. The high-salt diet significantly
      increased the baroreceptor-unloaded RSNA more than the regular-salt diet did, in
      both salt-sensitive and salt-resistant rats. After administration of the vehicle
      for 7-nitroindazole (peanut oil), L-arginine (100 micromol/kg per min for 10 min)
      decreased both resting and baroreceptor-unloaded RSNA, whereas after pretreatment
      with 7-nitroindazole, the L-arginine-induced suppression was reversed, in Dahl
      salt-sensitive rats receiving a high-salt diet. CONCLUSIONS: Neuronal nitric
      oxide may suppress the sympathetic discharge generated before baroreflex-mediated
      inhibition in all rats. This neuronal nitric oxide-mediated suppression was
      enhanced by the salt load in both salt-resistant and salt-sensitive Dahl rats.
      Finally, the neuronal nitric oxide-mediated suppression in tonic peripheral
      sympathetic outflow may be greatly enhanced in salt-sensitive hypertension.

PMID- 11327640
TI  - Effects of high sodium intake on cardiovascular aldosterone synthesis in stroke
      prone spontaneously hypertensive rats.
AB  - OBJECTIVES: Aldosterone is synthesized in extra-adrenal tissues such as the
      vasculature, heart and brain. The mechanisms underlying the effect of high salt
      intake on the development and acceleration of vascular injury and cardiac
      hypertrophy in the stroke-prone spontaneously hypertensive rats (SHRSP) are still
      not clear. The goal of this study was to determine whether high salt intake
      increases cardiovascular aldosterone synthesis in SHRSP. METHODS: Four-week-old
      SHRSP were given tap water or 0.9% NaCl solution for hydration for 4 weeks in
      addition to a normal salt diet. Isolated rat mesenteric arteries and hearts were
      perfused for 2 h, and the perfusate was analysed by high-performance liquid
      chromatography. The concentrations of aldosterone synthase gene (CYP11B2) mRNA
      and angiotensin II receptor (AT1R) mRNA were determined by competitive polymerase
      chain reaction. RESULTS: Salt-loaded SHRSP had higher blood pressures than SHRSP
      with normal salt intake. Plasma aldosterone concentrations and plasma renin
      activity were decreased by high salt intake. Aldosterone production, the
      expression of CYP11B2 mRNA and AT1R mRNA in mesenteric arteries and hearts were
      significantly increased by high salt intake. CONCLUSIONS: These results suggest
      that high salt intake increases aldosterone production and expression of the AT1R
      mRNA in the cardiovascular tissue in SHRSP, which may contribute to the
      development of malignant hypertension in salt-loaded SHRSP.

PMID- 11327641
TI  - Flow-mediated dilatation of the brachial artery and left ventricular geometry in
      hypertensive patients.
AB  - OBJECTIVES: In arterial hypertension, the spectrum of geometric patterns in the
      left ventricle may parallel the structural alterations detected in the carotid
      arteries and in subcutaneous small arteries. It has been also reported that
      hypertensive left ventricular hypertrophy (LVH) may be associated with
      endothelial dysfunction, as evaluated by the response of coronary or forearm
      vasculature to acetylcholine infusion. The aim of this study was to evaluate the
      flow-mediated vasodilatation (FMD) of the brachial artery, non-invasive estimate
      of endothelium-dependent vasodilatation according to left ventricular geometric
      adaptations in hypertensive patients. METHODS AND RESULTS: In 16 normotensive
      (nine males, seven females, aged 40-68 years) and in 78 hypertensive subjects (50
      males, 28 females, aged 42-67 years), we performed an echocardiographic study for
      the measurement of left ventricular mass index (LVMI) and relative wall thickness
      (RWT); we measured to a high resolution the brachial artery diameter at rest,
      during reactive hyperaemia (5 min of brachial artery occlusion) and after
      sublingual glyceril trinitrate (GTN); brachial artery flow velocity was measured
      by pulsed Doppler. Twenty-six hypertensive patients had a normal LVMI (LVMI < 51
      g/ m2.7) and geometry (RWT < 0.44), five had concentric remodelling (RWT > or =
      0.44), and concentric and eccentric LVH were observed in 19 and 28 patients,
      respectively. FMD was reduced in hypertensive patients as compared with
      normotensive subjects (P< 0.01). No correlation was found between FMD and LVMI
      (r= -0.078) or RWT (r = 0.049); in addition, no difference in FMD was found among
      the left ventricular geometric patterns in hypertensive patients. CONCLUSIONS: In
      hypertensives, the presence of endothelial dysfunction is not associated with the
      LVH or with different left ventricular geometric patterns, suggesting that
      different and independent mechanisms may be responsible for the presence of LVH
      and of endothelial dysfunction.

PMID- 11327642
TI  - Effects of activation of vasopressin-V1-receptors on regional kidney blood flow
      and glomerular arteriole diameters.
AB  - OBJECTIVES: We tested whether vasoconstriction of juxtamedullary glomerular
      arterioles contributes to vasopressin V1 -receptor-mediated reductions in
      medullary perfusion (MBF). DESIGN AND METHODS: The left kidney of pentobarbitone
      anaesthetized rabbits was denervated, a perivascular flow probe placed around the
      renal artery and laser-Doppler flow probes positioned in the inner medulla and on
      the cortical surface. Rabbits then received a 30 min intravenous infusion of
      [Phe2,Ile3,Orn8]vasopressin (V1 -AG; 30 ng/kg per min; n = 7) or its vehicle (n =
      7). Kidneys were perfusion fixed at the final recorded mean arterial pressure
      (MAP) and filled with methacrylate casting material. Diameters of afferent and
      efferent arterioles were determined by scanning electron microscopy. RESULTS: V1 
      AG increased MAP (19 +/- 3%) and reduced MBF (30 +/- 8%) but not cortical
      perfusion or total renal blood flow. Vehicle-treatment did not significantly
      affect these variables. After vehicle- and V1-AG-treatment, juxtamedullary
      afferent arteriole luminal diameter averaged 15.35 +/- 1.31 and 15.88 +/- 1.86
      microm, respectively (P= 0.92), while juxtamedullary efferent arteriole luminal
      diameter averaged 17.75 +/- 1.86 and 18.36 +/- 2.24 microm, respectively (P=
      0.93). CONCLUSIONS: V1-AG reduced MBF but did not significantly affect
      juxtamedullary arteriolar diameter. Our results therefore do not support a role
      for juxtamedullary arterioles in producing V1-receptor-mediated reductions in
      MBF, suggesting that downstream vascular elements (e.g. outer medullary
      descending vasa recta) might be involved.

PMID- 11327643
TI  - Effects of the ET(A)/ET(B) antagonist, TAK-044, on blood pressure and renal
      excretory function after unclipping of conscious one-kidney-one-clip hypertensive
      rats.
AB  - BACKGROUND: Restoring renal perfusion pressure (unclipping) of one-kidney-one
      clip renal hypertensive (1 K1C) rats normalizes mean arterial pressure (MAP)
      rapidly. This has been attributed to salt/volume losses or release of the
      putative renal medullary depressor hormone (RMDH). OBJECTIVE: To investigate the
      effects of endothelin receptor A and B (ET(A)/ET(B)) antagonism on unclipping.
      DESIGN AND METHODS: Telemetric devices were implanted in male Wistar 1K1C rats
      for measurement of conscious MAP. Hypertension was reversed by unclipping with
      the animal under brief anaesthesia. Seven rats were treated with the ET(A)/ET(B)
      antagonist, TAK-044 (two doses of 10 mg/kg intraperitoneally in 24 h), and eight
      rats received its vehicle. In order to investigate whether endothelin receptor
      antagonism could release RMDH under resting conditions, TAK-044 was administered
      to telemetered non-clipped intact and chemically renal medullectomized rats (BEA
      treatment). RESULTS: TAK-044 did not affect resting MAP, urine flow or sodium
      excretion in 1K1C rats. However, after unclipping, the TAK-044-treated group
      showed a more marked reduction in MAP during the first 24 h after unclipping (P<
      0.01). TAK-044 also reduced urine flow and sodium excretion during the first 8 h
      after unclipping (P< 0.05). TAK-044 reduced resting MAP (P< 0.05) to a similar
      extent in intact and BEA rats. CONCLUSIONS: TAK-044 potentiated the reduction in
      MAP after unclipping, independently of changes in urine flow and sodium
      excretion. It also reduced MAP in normotensive rats--an effect that was not
      dependent on an intact renal medulla. Potentiation of the depressor response to
      unclipping by TAK-044 could be the result of an interaction of endogenous
      endothelin receptors with renal depressor mechanisms--possibly, the release,
      actions, or both, of the putative RMDH.

PMID- 11327645
TI  - Modern management for veterinary practice.

PMID- 11327644
TI  - Foot-and-mouth disease: MAFF targets report-to-slaughter times in attempting to
      bring the disease under control.

PMID- 11327646
TI  - Use of valnemulin in the control of Mycoplasma bovis infection under field
      conditions.
AB  - In a blind trial, alternate calves in six consecutive production batches of
      calves (total 70), on a farm with a high incidence of respiratory and
      reproductive disease, were allocated to treatment with either valnemulin or a
      placebo premix added to the milk from four days of age. The calves were weighed
      at the beginning and end of a 21-day period of medication. Blood samples and
      nasal swabs were taken and examined for the presence of Mycoplasma and
      Pasteurella species, and antibodies to viral agents. Clinical condition, rectal
      temperature, respiratory and other signs and refusals of milk were recorded
      daily. Dead calves were examined postmortem. The calves medicated with valnemulin
      gained weight more quickly, had fewer cases of Mycoplasma infection and fewer
      respiratory signs, and required fewer treatments with antibiotics than those in
      the placebo group.

PMID- 11327647
TI  - Serum alpha-tocopherol concentrations in German shepherd dogs with chronic
      degenerative radiculomyelopathy.
AB  - The concentration of serum alpha-tocopherol was measured in German shepherd dogs
      with chronic degenerative radiculomyopathy, and in German shepherd dogs and dogs
      of other breeds unaffected by the condition. The mean concentration was
      significantly higher in German shepherd dogs with the condition than in other
      breeds of dog unaffected by it, but it was not significantly higher than in
      unaffected German shepherd dogs. Estimates of components of variance indicated
      that the concentration varied more widely in individual affected dogs than in
      unaffected dogs, irrespective of breed. These results suggest that chronic
      degenerative radiculomyopathy in German shepherd dogs is unlikely to be due to
      uncomplicated vitamin E deficiency.

PMID- 11327648
TI  - Seroprevalence and antibiotic sensitivity of serotypes of Salmonella enterica in
      Greek pig herds.
AB  - Blood samples were taken from 50 pigs in each of 59 farrow-to-finish production
      herds and from 40 pigs in each of four of five registered multiplying herds.
      Samples of feed and faeces were also collected from 17 of the production herds
      and from the four multiplying herds. The sera were tested for antibodies to
      Salmonella enterica by the Danish mix-ELISA, and the organisms were isolated,
      serotyped and sensitivity tested by standard techniques. The average within-herd
      seroprevalence was 3.4 per cent and at least one pig tested seropositive in 21 of
      the 59 herds. In the multiplying herds, only a single seroreactor was detected.
      Salmonellae were isolated from only five of 95 feed samples, from two of the 17
      herds sampled, Salmonella tennessee in four of five samples from one herd and an
      untypable strain in one of five samples from another. Four infected faecal
      samples were detected in four herds; they harboured Salmonella typhimurium,
      Salmonella bredeney or Salmonella london. No salmonellae were isolated from the
      samples of feed and faeces taken from the multiplying herds. The S london and S
      typhimurium had a low sensitivity to streptomycin, kanamycin and neomycin, and
      the S typhimurium also had low sensitivity to amoxycillin, ticarcillin,
      piperacillin, amoxycillin + clavulanic acid, cefalotin and cefoperazone. The
      other isolates were sensitive to all the antimicrobial agents tested.

PMID- 11327649
TI  - Ultrasound diagnosis and treatment outcome of cystic ovaries in cattle.

PMID- 11327650
TI  - Tuberculosis in an Iberian lynx (Lynx pardina).

PMID- 11327651
TI  - Seroprevalence of Leptospira serovars in Korean sows.

PMID- 11327652
TI  - Appointment of TVIs.

PMID- 11327653
TI  - Appointment of TVIs.

PMID- 11327654
TI  - Appointment of TVIs.

PMID- 11327655
TI  - Appointment of TVIs.

PMID- 11327656
TI  - Veterinary pharmacy.

PMID- 11327657
TI  - Corporate practice.

PMID- 11327658
TI  - Caryosporosis in snowy owls (Nyctea scandiaca).

PMID- 11327659
TI  - Breeding difficulties.

PMID- 11327660
TI  - ELISA for the diagnosis of canine sarcoptic mange.

PMID- 11327661
TI  - What is your diagnosis? Vesicourachal diverticulum.

PMID- 11327662
TI  - Photodynamic therapy of feline superficial squamous cell carcinoma using topical
      5-aminolaevulinic acid.
AB  - A study was undertaken to investigate the treatment of superficial squamous cell
      carcinoma of the nasal planum, pinna and eyelid in cats by photodynamic therapy,
      using topical 5-aminolaevulinic acid cream, with subsequent exposure to red light
      of wavelength 635 nm, supplied by a light-emitting diode source. A total of 13
      squamous cell carcinomas were treated, including 10 nasal planum lesions, two
      pinnal lesions and one eyelid lesion. After a single treatment, complete
      responses were seen in nine out of 10 nasal planum lesions, one out of two pinnal
      lesions and the eyelid lesion. The overall complete response rate for lesions
      managed with a single photodynamic therapy treatment was 85 per cent. Seven of
      the 11 lesions (63.6 per cent) showing a complete response subsequently recurred;
      the time to recurrence ranged from 19 to 56 weeks (median 21 weeks, mean 26.7
      weeks).

PMID- 11327663
TI  - Activity of amphotericin B in lipid emulsion in the initial treatment of canine
      leishmaniasis.
AB  - Amphotericin B was given to 19 dogs with leishmaniasis. The drug was diluted in
      an emulsion prepared by mixing 50 mg of amphotericin B desoxycholate with 40 ml
      of sterile water and 10 ml of soya bean oil solution. The dogs were infused over
      nearly one hour with 50 ml/kg of normal saline followed by 10 ml/kg of mannitol
      20 per cent. The mixture was then loaded over 30 to 60 minutes using a syringe
      pump. The emulsion was given twice weekly, at an increasing dosage (from 1 to 2.5
      mg/kg bodyweight), for a minimum of eight injections. All 17 dogs receiving a
      total dosage of more than 10 mg/kg were clinically cured by the end of the
      treatment, and 14 of these had a negative polymerase chain reaction test on bone
      marrow.

PMID- 11327664
TI  - Effect of low levels of dietary tyrosine on the hair colour of cats.
AB  - Experiments were conducted to investigate the basis for the change in hair colour
      of black cats to reddish-brown. Black cats were given purified diets based on
      gelatin, casein plus lactalbumin, or crystalline amino acids as protein sources.
      Diets that caused the colour of hair to change to reddish-brown were associated
      with a reduction in melanin in hair (observed by direct microscopic examination),
      a decreased total melanin concentration and low concentrations of tyrosine in
      plasma. Reddish hair coat was induced in black kittens born to queens given a
      tyrosine-deficient diet during pregnancy. Black hair colour was maintained or
      restored by diets containing a high concentration of tyrosine or phenylalanine.
      Current dietary recommendations for dietary tyrosine and phenylalanine for cats
      are below those required to support maximal melanin synthesis in black cats. The
      requirement appears to be greater than a combination of 4.5 g tyrosine plus 12 g
      phenylalanine/kg diet but less than 24 g phenylalanine alone/kg diet.

PMID- 11327665
TI  - Copper toxicosis in the Bedlington terrier: a diagnostic dilemma.
AB  - Diagnosis of copper toxicosis (CT) in Bedlington terriers by the quantitative and
      qualitative assessment of copper (Cu) in, and pathology of, biopsies has been
      largely superseded by a DNA-based assay which uses a microsatellite marker
      (C04107) linked to the CT disease allele. A retrospective study was conducted
      comprising 154 liver biopsies from Bedlington terriers with 22 matched DNA
      markers to compare the two methods in the diagnosis of CT. For the biopsy method,
      three categories (phenotypes) were identified based on analytical and
      morphological criteria: 'unaffected' in 83 samples (54 per cent), where Cu was
      much less than 400 microg/g, and there was an absence of visual Cu or liver
      damage; 'intermediate' in 18 samples (12 per cent), where Cu was less than 400
      microg/g, and there was limited histochemical Cu and no/equivocal damage; and
      'affected' in 53 samples (34 per cent), where Cu was greater than 400 microg/g,
      there was histochemical Cu and liver damage was poorly related to Cu content. In
      the DNA assay, which was used alone on unrelated individuals, the microsatellite
      marker failed to identify the CT status of any of the groups. Liver biopsy
      remains a reliable indicator of Cu accumulation and progressive liver disease in
      individual dogs. The microsatellite marker C04107 has a predictive value only
      when supported by a pedigree.

PMID- 11327666
TI  - Hypoadrenocorticism in a cat.
AB  - Primary hypoadrenocorticism was diagnosed in an eight-year-old neutered male cat.
      The predominant presenting complaint was dysphagia. Other historical signs
      included lethargy, weight loss, polydipsia, polyuria, muscle weakness and
      occasional vomiting. The signs had waxed and waned over the two months before
      presentation and had improved when the cat was treated with enrofloxacin and
      prednisolone by the referring veterinarian. On referral, dehydration, depression
      and poor bodily condition were found on physical examination. Results of initial
      laboratory tests revealed mild anaemia, hyperkalaemia, hyponatraemia,
      hypochloraemia and elevations in serum creatinine and creatine kinase. The
      diagnosis of primary adrenocortical insufficiency was established on the basis of
      results of an adrenocorticotropic hormone (ACTH) stimulation test and endogenous
      plasma ACTH determination. Initial therapy for hypoadrenocorticism included
      intravenous administration of 0.9 per cent saline and dexamethasone, and oral
      fludrocortisone acetate. Within one week the cat was clinically normal and two
      years later was still alive and well on fludrocortisone acetate treatment only.

PMID- 11327667
TI  - Budd-Chiari-like syndrome associated with an adrenal phaeochromocytoma in a dog.
AB  - A nine-year-old dog was presented with sudden-onset ascites and a history of two
      previous syncopal episodes. Diagnostic tests pointed to a Budd-Chiari-like
      syndrome, with obstruction of the caudal vena cava between the liver and heart.
      The ascites was refractory to treatment and the dog was euthanased. On postmortem
      examination, a phaeochromocytoma of the left adrenal gland was present, with
      contiguous invasions into the caudal vena cava, extending cranially as far as the
      cavoatrial junction. To the authors' knowledge, this is the first reported case
      of a Budd-Chiari-like syndrome associated with a phaeochromocytoma in a dog.

PMID- 11327668
TI  - Fatal pulmonary fat embolism during humeral fracture repair in a cat.
AB  - An 11-month-old cat was referred following a road traffic accident with non
      weightbearing forelimb lameness and tachypnoea. A diaphragmatic rupture was
      repaired two days after trauma. Six days post trauma, a further operation was
      performed to repair the fractured humerus. As an intramedullary pin was advanced
      into the bone to achieve stabilisation, acute respiratory arrest occurred. Manual
      extrathoracic cardiopulmonary resuscitation was immediately instigated, but the
      cat did not recover. Postmortem examination identified a high degree of embolic
      fat occluding pulmonary capillaries. A massive embolic shower was established as
      the cause of death.

PMID- 11327669
TI  - Collie eye anomaly in the rough collie.

PMID- 11327670
TI  - Emerging diseases in northern Europe.

PMID- 11327671
TI  - Challenges in companion animal welfare.

PMID- 11327672
TI  - Are cell phones bad for your health?

PMID- 11327673
TI  - Anterior chamber angle anomalies associated with signs of pigment dispersion in a
      group of black probands and their first-degree relatives.
AB  - PURPOSE: To evaluate the presence of iridocorneal angle anomalies associated with
      signs of pigment dispersion among a group of black probands and their first
      degree relatives. METHODS: Eleven blacks who exhibited pigment dispersion
      syndrome (PDS) signs, including Krukenberg's spindles, moderate-to-heavy
      trabecular meshwork pigmentation, and peripheral lenticular/zonular pigmentation,
      received a complete eye examination that included gonioscopy. Overt iridocorneal
      angle abnormalities other than pigment deposition were photo-documented. Twenty
      two first-degree relatives (6 siblings, 15 children, and 1 parent) of these
      probands underwent similar examination. RESULTS: Among the subjects, 5 of 11
      probands (age range 13 to 59 years) and 4 of 22 relatives (age range 14 to 51
      years) exhibited definite angle anomalies. The nine subjects with angle anomalies
      belonged to 7 of 11 separate families. The four relatives with angle anomalies
      did not have PDS according to our criteria, but two other relatives from two
      additional families did have signs consistent with clinical PDS. Types of angle
      anomalies included (1) peripheral anterior synechia-like lesions; (2) a prominent
      concavity of the peripheral iris at the 6-o'clock meridian; (3) a whitish, thread
      like band of tissue near the iris base; (4) a prominent, externally-visible
      Schwalbe's line at the 6-o'clock meridian; and (5) a prominent, web-like
      confluence of exaggerated iris processes 360 degrees along the angle wall. Iris
      processes and prominent Schwalbe's lines were not considered abnormal or
      anomalous unless they were clearly atypical. CONCLUSIONS: Iridocorneal angle
      anomalies, other than pigment deposition, were common among our black group who
      exhibited signs of pigment dispersion as well as among their first-degree
      relatives. Further consideration should be given to the possibility that among
      some patient groups, overt goniodysgenesis could be part of a constellation of
      signs indicative of a pigment dispersion syndrome. Potentially, clinically
      detectable goniodysgenesis could prove to be a useful marker to identify certain
      subjects who carry PDS genetic traits but who have not expressed complete
      phenotypical disease.

PMID- 11327674
TI  - What does the phenol red thread test actually measure?
AB  - PURPOSE: This study attempts to resolve whether the phenol red thread test (PRT)
      is a test of tear volume or tear production through comparisons with other
      techniques. METHODS: Twenty asymptomatic subjects (10 men and 10 women; average
      age 30.6 +/- 10.8 years) had PRT (Zone Quick, Menicon) results compared with tear
      turnover rate (by fluorophotometry; Fluorotron Master, OcuMetrics) and tear
      volumes (from tear meniscus height and back extrapolation from fluorometric
      data). RESULTS: PRT wetting was not correlated with either tear turnover or
      volume (by fluorophotometry or tear meniscus height) on a Pearson product moment
      correlation test (p > 0.05). CONCLUSIONS: No clear experimental evidence in favor
      of the PRT being a measure of tear production or volume was found. It is probable
      that the PRT measures uptake of a (small) amount of fluid residing in the eye,
      stimulates a low degree of reflex tearing, and reflects the absorption
      characteristics of the thread dependent on the biophysics or composition of
      tears.

PMID- 11327676
TI  - Comparing laser ray tracing, the spatially resolved refractometer, and the
      Hartmann-Shack sensor to measure the ocular wave aberration.
AB  - PURPOSE: To compare quantitatively three techniques to measure the optical
      aberrations of the human eye: laser ray tracing (LRT), the Hartmann-Shack
      wavefront sensor (H-S), and the spatially resolved refractometer (SRR). LRT and H
      S are objective imaging techniques, whereas SRR is psychophysical. METHODS: Wave
      aberrations were measured in two normal subjects with all three techniques
      implemented in two different laboratories. RESULTS: We compared the experimental
      variability of the results obtained with each technique with the overall
      variability across the three methods. For the two subjects measured (RMS
      wavefront error 0.5 microm and 0.9 microm, respectively), we found a close
      agreement; the average standard deviation of the Zernike coefficients within a
      given method was 0.07 microm, whereas the average global standard deviation
      across techniques was 0.09 microm, which is only slightly higher. CONCLUSIONS:
      There is a close match between the Zernike coefficients obtained by LRT, H-S, and
      SRR. Thus, all three techniques provide similar information concerning wave
      aberration when applied to normal human eyes. However, the methods are
      operationally different, and each has advantages and disadvantages depending on
      the particular application.

PMID- 11327675
TI  - Vascular response to extended wear of hydrogel lenses with high and low oxygen
      permeability.
AB  - PURPOSE: The purpose of this study was to determine the impact of extended wear
      of high and low oxygen permeability (Dk) lenses on the development or resolution
      of limbal hyperemia and corneal neovascularization in a randomized prospective
      clinical trial. METHODS: Adapted daily-wear contact lens wearers were randomly
      assigned to one of two groups. The low-Dk group (N = 23) wore etafilcon A lenses
      (Dk/t = 40) for up to 7 days and 6 nights, and the high-Dk group (N = 39) wore
      lotrafilcon A lenses (Dk/t = 175) for up to 30 days and nights. Limbal hyperemia
      and neovascularization were assessed and graded during 9 months of extended wear.
      A stratified analysis to determine how change in ocular redness depended on
      initial presentation was also conducted. RESULTS: On a 0 to 100 scale, extended
      wear of low-Dk lenses resulted in a 16-point increase in limbal hyperemia (p <
      0.0001); no significant change occurred with the high-Dk lenses. The difference
      was greatest for low-Dk participants who initially presented with lower levels of
      hyperemia (N = 18). There was a slight resolution of redness in participants who
      initially presented with higher levels of hyperemia (N = 10) after wearing the
      high-Dk lenses. Neovascularization increased by an average of 0.5 on a scale of 0
      to 4 in low-Dk lens wearers (p < 0.0001) but remained unchanged in the high-Dk
      lens wearers. The increase was most marked for the low-Dk group with lower levels
      of neovascularization at baseline. CONCLUSIONS: Subjects who wore lenses with
      higher oxygen permeability for 9 months of extended wear exhibited a lower
      vascular response of the ocular surface compared with subjects who wore lenses of
      lower oxygen permeability for the same period. This result was found both for the
      surface limbal vessels and in the deeper neovascular stromal vessels. Moderate
      neovascularization also developed after 3 months of extended wear of low-Dk
      hydrogels, whereas high-Dk lenses caused no neovascularization.

PMID- 11327677
TI  - Contrast sensitivity function in patients with impaired oral glucose tolerance.
AB  - PURPOSE: To evaluate contrast sensitivity function in patients with impaired oral
      glucose tolerance test (OGTT) compared with normal subjects. METHODS: Sixteen
      patients with impaired OGTT and 11 normal control subjects were tested for
      contrast sensitivity function at four spatial frequencies. Glucose intolerance
      was established by the 1985 World Health Organization criteria. RESULTS: The two
      groups were similar in terms of age, visual acuity, refractive correction, and
      lens opacities. A statistically significant loss of contrast sensitivity was
      associated with impaired OGTT (p < 0.001) in every spatial frequency tested.
      CONCLUSIONS: Functional visual loss in patients with impaired glucose tolerance
      using the 1985 World Health Organization criteria indicates that at least part of
      those patients should be classified as diabetic according to the 1997 American
      Diabetic Association criteria. It seems that the 1997 American Diabetic
      Association criteria are more efficient at detecting patients with abnormal
      visual function.

PMID- 11327678
TI  - Retinal illuminance and the dissociation of letter and grating acuity in age
      related macular degeneration.
AB  - PURPOSE: To report on the differential effect of retinal illuminance on letter
      and grating acuity. METHODS: For 13 subjects with age-related macular
      degeneration (ARMD) and four subjects with normal vision, standard distance and
      near letter acuity, as well as grating acuity data were obtained at mesopic to
      high-photopic light levels. RESULTS: In general, both acuity forms improved with
      increasing light level, but not in proportion with one another. The ratio of
      letter/grating acuity separated the ARMD subjects into two subgroups, one with
      relatively low letter acuity scores for which the dissociation of the two acuity
      forms increased with retinal illuminance, and another with higher letter acuity
      values for which the ratio converged toward unity. CONCLUSIONS: These findings
      demonstrate that both letter and grating acuity increase with retinal illuminance
      and that equating grating acuity with optotype acuity is untenable in subjects
      with ARMD, irrespective of light levels. The latter conclusion is of importance
      whenever acuity is used as a criterion to classify the visually impaired with
      regard to their legal and social status.

PMID- 11327679
TI  - Duration thresholds for target detection and identification in the peripheral
      visual field.
AB  - PURPOSE: In the current study, we measured threshold duration required to perform
      the tasks of letter identification, letter detection, grating orientation
      discrimination, and symmetry detection of targets presented as a function of
      retinal eccentricity. METHODS: Targets were presented in the nasal visual field
      on the horizontal meridian at eccentricities ranging from 0 degree to 22 degrees.
      Threshold duration was calculated using a modified staircase procedure. RESULTS:
      We found that for the task of letter identification, the rate of duration
      sensitivity loss was independent of the letter size. In contrast, for the tasks
      of letter detection, grating discrimination, and symmetry detection, the rate of
      loss was greater for smaller targets than for larger targets. CONCLUSION: At
      equivalent target sizes, letter identification always demonstrated the steepest
      decline in duration sensitivity with increasing eccentricity. This might be the
      case if the final stages of the identification process are rate limiting. It was
      hoped that by quantifying duration sensitivity of the peripheral retina, more
      appropriate temporal stimuli could be used in rehabilitation programs that train
      reading using eccentric preferred retina loci in patients with advanced macular
      disease.

PMID- 11327680
TI  - Activation of follicle development: the primordial follicle.
AB  - Investigations of primordial follicle formation and growth are fundamental to our
      understanding of female gamete production. In all mammalian females the full
      complement of oocytes is established during fetal development. This store of
      primordial follicles is not renewable and serves the entire reproductive life
      span of the adult. The correct programming of fetal ovarian development and the
      number of primordial follicles formed will therefore limit the fecundity of the
      ovary. Primordial follicles are characterized by the presence of a single oocyte
      surrounded by a varying number of pregranulosa cells. The relatively small size,
      undifferentiated status and large numbers of primordial follicles make them prime
      candidates for use in basic and applied research in animal production, gene
      transfer and cloning. Furthermore, the development of cell culture systems that
      use primordial follicles as a source of oocytes for in vitro growth and
      maturation will enable us to maximize the potential of high genetic merit females
      and to shorten generation intervals. Despite these possibilities, primordial
      follicles are the least understood of all stages of follicle development. The
      factor(s) responsible for maintaining the primordial pool or, conversely, for
      activating primordial follicle growth remain elusive.

PMID- 11327681
TI  - Regulation of ovarian follicular dynamics in farm animals. Implications for
      manipulation of reproduction.
AB  - In this review, the main features of folliculogenesis are summarized and compared
      among species. In the past few years, ultrasonography has clarified follicle
      growth patterns, and our understanding of follicle maturation has improved
      considerably. As the follicles develop towards the ovulatory stage, three
      features appear to be highly conserved across all species: 1) the sequence of
      events (recruitment, selection and dominance); 2) the sequential need for
      gonadotropins (FSH for recruitment, LH for dominance) and 3) the large
      variability of numerical parameters (number of waves per cycle, number of
      follicles per wave) as well as temporal requirements (time of selection, duration
      of dominance). In addition, specific follicles may also have variable
      gonadotropin requirements (thresholds). When patterns of follicle development at
      different physiological states are compared across species, follicular waves were
      detected in cattle, sheep and horses and during the prepubertal period in swine,
      suggesting that ovaries of all species operate on a wave basis unless they are
      prevented from doing so. Efficient estrus control treatments should have the
      ability to affect 1) the wave pattern by preventing the development of persistent
      dominant follicles containing aging oocytes, and 2) the recruitment of the future
      ovulatory follicle whatever the stage of the wave at the time of treatment. This
      would allow synchronous ovulation of a growing dominant follicle. Manipulation of
      the luteal phase follicular waves after mating or AI may also optimize fertility.
      Superovulation is still an efficient technique to obtain progeny from genetically
      valuable females. Administration of exogenous gonadotropins acts to reveal the
      underlying ovarian variability. Ovarian response of each female depends on the
      number of gonado-sensitive follicles present at the time when treatment is
      initiated. Identification of the number of such follicles for each female would
      improve efficacy of superovulation, by allocating potential nonresponders to
      other techniques (OPU/FIV). One of the main components of the within female
      response to superovulation is the stage of the wave when gonadotropins are
      injected. Treatment in the absence of a dominant follicle ensures a response
      close to the female's specific maximum. The development of practical approaches
      to achieve this still requires further research.

PMID- 11327682
TI  - Resumption of meiosis: mechanism involved in meiotic progression and its relation
      with developmental competence.
AB  - It has been more than 10 years since the first calf was born following in vitro
      maturation of a bovine oocyte. During that period, a number of modifications have
      been made to the culture conditions during the maturation period but still most
      oocytes failed to produce viable embryos. Recently, the pretreatment of donors
      leading to clear improvements in oocyte developmental competence has been
      achieved. These treatments can be either 1) ovarian stimulation with FSH followed
      by the slaughter of the animal and the incubation of ovaries before oocyte
      aspiration or 2) the transvaginal aspiration of oocytes from FSH-stimulated
      animals following a "coasting period" of 48 hours. These 2 treatments indicate
      the necessity of preparing the immature oocyte before using it. An alternative to
      the animal pretreatment would be to recreate in vitro the conditions present in
      more mature follicles. It is believed that the ability of the oocyte to become an
      embryo depends on the accumulation of specific information in the form of mRNA or
      proteins. Because the consequences of that change become visible 4 days later at
      the early 8-cell stage, the favorite hypothesis is that the oocyte accumulates
      stable mRNA and that accumulation requires an active transcription machinery.
      Therefore, to improve oocyte's potential, follicular instructions must be given
      before the germinal vesicle breakdown induced by oocyte aspiration and culture.
      The culture of bovine oocytes in a state of meiotic arrest could potentially
      allow the correct follicular signal(s) to change the development potential of an
      oocyte. The unraveling of the mechanism for cell control of meiotic arrest opens
      the way to a functional and reversible culture system for immature oocytes. The
      remaining challenge is to discover follicular signals or factors to apply during
      the in vitro culture period to enhance the competence of oocytes.

PMID- 11327683
TI  - The maternal legacy to the embryo: cytoplasmic components and their effects on
      early development.
AB  - RNA molecules and proteins are accumulated in the oocyte cytoplasm during its
      growth phase and are used to sustain the early phases of embryonic development
      before embryo DNA transcription begins. This makes the oocyte a very special
      cell, quite different from somatic cells where RNA and proteins usually undergo a
      rapid turnover. To enable the storage and timely use of such stored molecules,
      various mechanisms are effective in the oocyte and are gradually being
      elucidated. Our understanding of such mechanisms is important for constantly
      improving therapy for human and animal reproductive disorders as well as for
      understanding the process of nuclear reprogramming during cloning procedure or
      stem cell generation. This review focuses on the various aspects of these
      regulatory processes in an attempt to give an overview of the present knowledge
      on post-transcriptional and post-translational mechanisms taking place during
      oocyte maturation and early development. Mechanisms such as cytoplasmic
      regulation of the poly(A) tail, RNA localization and protein phosphorylation are
      described in some detail. Because most data are available from lower species
      these are presented together with appropriate reference to the mammalian oocyte
      when data are known, or when important differences have been described.

PMID- 11327684
TI  - The developmental competence of mammalian oocytes: a convenient but biologically
      fuzzy concept.
AB  - Oocyte developmental competence is often used to qualify in vitro procedures for
      embryo production. It supposedly accounts for the oocyte's ability to develop
      into a normal, viable and fertile offspring after fertilization, but for
      practical reasons it often characterizes the ability of such oocytes to develop
      to the blastocyst stage in vitro. Molecular tools compatible with the analysis of
      very small amounts of material have resulted in research aimed at designing
      molecular criteria to define this competence. However we feel that such research
      strategies easily lead to misunderstanding of the regulative processes that drive
      embryo development. Artificially induced blastocyst stage is a poor predictor of
      oocyte developmental competence. However preimplantation stages also appear to be
      sensitive to environmental conditions that can induce long-lasting detrimental
      effects. Larger scale analysis now made available by a functional genomics
      approach provides a more accurate understanding of the complex regulative
      networks that sustain the molecular mechanisms responsible for normal
      development. We propose that the concept of developmental competence should be
      used more cautiously and also should refer more explicitly to the experimental
      context it intends to enlighten.

PMID- 11327685
TI  - The improvement of in vitro maturation systems for bovine and porcine oocytes.
AB  - Recent advances in biotechnology have enabled us to produce cloned and
      genetically modified cattle and pigs by manipulating in vitro-produced embryos.
      However, the efficiency is still extremely low, mainly because of the low
      developmental competence of manipulated embryos. To improve this situation, IVM
      systems for bovine and porcine oocytes in in vitro embryo production systems must
      be improved. This paper addresses the selection of ovaries with competent
      follicles at a slaughterhouse and looking attached sight of oocytes at a lab, and
      the IVM of oocytes under redox state to enhance the developmental competence of
      IVM oocytes in cattle and pigs.

PMID- 11327686
TI  - Effects of maternal age on oocyte developmental competence.
AB  - The widespread use of a variety of assisted reproductive technologies has removed
      many of the constraints that previously restricted mammalian reproduction to the
      period between onset of puberty and reproductive senescence. In vitro embryo
      production systems now allow oocytes from very young animals to undergo
      fertilization and form embryos capable of development to normal offspring, albeit
      at somewhat reduced efficiencies compared to oocytes from adult females. They
      also can overcome infertility associated with advanced age of animals and women.
      This review examines oocyte developmental competence as the limiting factor in
      applications of assisted reproductive technologies for both juvenile and aged
      females. Age of oocyte donor is a significant factor influencing developmental
      competence of the oocyte. Age-related abnormalities of oocytes include a) meiotic
      incompetence or inability to complete meiotic maturation resulting in oocytes
      incapable of fertilization; b) errors in meiosis that can be compatible with
      fertilization but lead to genetic abnormalities that compromise embryo viability;
      and c) cytoplasmic deficiencies that are expressed at several stages of
      development before or after fertilization. In general, oocytes from juvenile
      donors and the embryos derived therefrom appear less robust and may be less
      tolerant to suboptimal handling and in vitro culture conditions than are adult
      oocytes. Research to identify specific cytoplasmic deficiencies of juvenile
      oocytes may enable modifications of culture conditions to correct such
      deficiencies and thus enhance developmental competence. Use of oocytes from aged
      donors for assisted reproduction can have a variety of applications such as
      extending the reproductive life of individual old females whose offspring still
      have high commercial value, and conservation of genetic resources such as rare
      breeds of livestock and endangered species. In general, female fertility
      decreases with advancing age. Studies of women in oocyte donation programs have
      established reduced oocyte competence as the major cause of declining fertility
      with age, although inadequate endometrial function can also be a contributing
      factor. Most research has emphasized the importance of chromosomal abnormalities
      because of the well established increase in aneuploidy with increasing maternal
      age but little is known about the underlying cellular and molecular mechanisms.
      Research aimed at identifying the specific developmental deficiencies of oocytes
      from juvenile donors and abnormalities of oocytes from aged females will assist
      in overcoming present bottlenecks that limit the efficiency of assisted
      reproduction technologies. Such research will also be crucial to the development
      of new oocyte-based technologies for overcoming infertility and possibly
      subverting chromosomal abnormalities in women approaching menopause.

PMID- 11327687
TI  - Effect of nutrition on endocrine parameters, ovarian physiology, and oocyte and
      embryo development.
AB  - Reproductive efficiency in high yielding dairy cows has decreased over the past
      50 years, despite significant gains in genetic selection for increased milk
      output. One possible reason for this decline has been a change in the nutritional
      intake to meet the increased energy and protein demands for higher milk
      production. Excess energy intake in sheep will lead to significant reductions in
      progesterone concentrations; the effects in cattle are not so clear. Nutrition,
      unless radically changed, will have little effect on gonadotropin concentrations
      in ruminants, and this is in contrast to the situation for pigs and for primates,
      where very short-term nutritional changes manifest themselves in altered
      gonadotropin secretion. Cattle with reduced energy intake have smaller dominant
      follicles and more three-wave cycles, compared with animals on higher feed
      intakes. One of the main areas where nutrition influences reproductive efficiency
      is at the level of embryo production. Several studies indicate that excess energy
      intake reduces the response to superovulation and also decrease the yield of
      embryos and alters expression of some gene constructs within the developing
      embryo. The mechanism of this effect is not clear but indications are that the
      quality of the oocytes may be compromised. Indeed recent data indicate that
      nutritional changes around the time of mating may have detrimental effects on the
      establishment of pregnancy in heifers. Thus, nutritional balancing is critical
      for high-yielding dairy cows, in particular. The challenge remains to modify
      nutritional and management strategies in such cows to maintain the levels of
      production made possible by genetic selection and still maintain an acceptable
      level of fertility.

PMID- 11327688
TI  - Embryo production by ovum pick up from live donors.
AB  - Embryo production by in vitro techniques has increased steadily over the years.
      For cattle where this technology is more advanced and is applied more, the number
      of in vitro produced embryos transferred to final recipients was over 30,000 in
      1998. An increasing proportion of in vitro produced embryos are coming from
      oocytes collected from live donors by ultrasound-guided follicular aspiration
      (ovum pick up, OPU). This procedure allows the repeated production of embryos
      from live donors of particular value and is a serious alternative to
      superovulation. Ovum pick up is a very flexible technique. It can be performed
      twice a week for many weeks without side effects on the donor's reproductive
      career. The donor can be in almost any physiological status and still be suitable
      for oocyte recovery. A scanner with a sectorial or convex probe and a vacuum pump
      are required. Collection is performed with minimal stress to the donor. An
      average of 8 to 10 oocytes are collected per OPU with an average production of 2
      transferable embryos. The laboratory production of embryos from such oocytes does
      not differ from that of oocytes harvested at slaughter as the results after
      transfer to final recipients. For other species such as buffalo and horses OPU
      has been attempted similarly to cattle and data will be presented and reviewed.
      For small ruminants, laparotomy or laparoscopy seems the only reliable route so
      far to collect oocytes from live donors.

PMID- 11327689
TI  - Oocyte cryopreservation and ovarian tissue banking.
AB  - Oocyte cryopreservation, despite its impact on conservation of genetic resources,
      is not yet an established technology. Several problems need to be solved before
      this technology can be applied regularly. Chilling membrane susceptibility and
      formation of ice due to the large volume of the cell are the major problems
      observed. However, during the last years, several studies were done to obtain
      viable oocytes after cryopreservation. The addition of molecules known to
      stabilize membranes and the creation of freezing systems with rapid cooling
      throughout the transition phase have yielded a good percentage of viable immature
      and mature oocytes More recently, storage of female gametes was achieved by
      cryopreservation of cortical ovarian tissue. The possibility of restoring
      fertility by transplantation of frozen ovarian tissue or its long-term culture in
      vitro represents an important future means of preserving the fertility of
      patients and of storing the gametes of rare animals.

PMID- 11327690
TI  - Nucleus transfer in mammals: how the oocyte cytoplasm modifies the transferred
      nucleus.
AB  - Successful development of clones depends on the reprogramming of transferred
      nuclei in enucleated oocytes. Thus far, oocytes are the only cells that can
      convert nuclei, which are already differentiated, into undifferentiated stages
      resembling pronuclei in freshly fertilized zygotes and that can then complete
      development of the reconstructed embryos. However, we still don't know exactly
      how the enucleated oocyte (cytoplast) secures this reprogramming. Oocytes exhibit
      a number of cytoplasmic activities that may be involved reprogramming. We discuss
      how these activities may be involved in reprogramming of transferred nuclei.

PMID- 11327691
TI  - Cytoplasmic inheritance and its implications for animal biotechnology.
AB  - At fertilization, the mammalian sperm transmits the haploid paternal genome.
      However, it also carries a variety of other factors into the oocyte that have the
      potential to affect embryo development. These include mRNAs left over from
      spermatogenesis, mitochondria with their own DNA, cytoskeletal and contractile
      elements, remnants of the sperm plasma membrane and, in many species, the sperm
      centriole. While most of these elements are eliminated, some play essential roles
      in early embryogenesis. In this review, I summarize the latest information on
      these phenomena and indicate some of the implications for animal biotechnology
      and, in particular, cloning.

PMID- 11327692
TI  - Cation radius effects on cell-free translation in rabbit reticulocyte lysate.
AB  - The effect of monovalent cation concentrations on the translation was examined in
      the rabbit reticulocyte cell-free system. The translation of standard reporter
      gene luciferase was studied using different concentrations of LiCl, NaCl, KCl,
      RbCl, CsCl, NH(4)Cl, and (CH(3))(4)NCl and the acetates of Na(+), K(+), and
      NH4(+). Only the salts of K(+), Rb(+), and NH4(+) and to some minor extent of
      Cs(+) significantly supported translation. Optimum concentrations were dependent
      on the cation used. Optimum concentrations ranged between 40 mM (NH(4)Ac), 80 mM
      (KCl, NH(4)Cl), and 100 mM (RbCl, KAc). The maximum efficiency of translation
      depends on the ionic radius of the cation used. KCl and RbCl were superior to all
      other salts tested in stimulating in vitro translation. The results were
      confirmed, using a second reporter system, M-hirudin. Here, however, broad optima
      were observed with RbCl being slightly superior to KCl in supporting translation.

PMID- 11327693
TI  - Tob-mediated cross-talk between MARCKS phosphorylation and ErbB-2 activation.
AB  - The biochemical path for the activation of ErbB-2 by PKC activator was
      investigated in MDA-MB-231 human breast cancer cells. We found that PMA-induced
      phosphorylation of myristoylated alanine-rich C kinase substrate (MARCKS)
      increased its binding with Tob that exerts an anti-proliferative effect through
      the binding with ErbB-2. The phosphorylation site domain (PSD) of MARCKS was
      relevant to its interaction with Tob. Decreased binding of Tob with ErbB-2 and
      subsequent activation of ErbB-2 were observed in MDA-MB-231 cells in response to
      PMA treatment. The present study proposes that MARCKS phosphorylation by PKC
      removes Tob from ErbB-2 by increasing its binding affinity with Tob, and thereby
      activates the ErbB-2 mediated signal transduction.

PMID- 11327694
TI  - Hyaluronidase activation of c-Jun N-terminal kinase is necessary for protection
      of L929 fibrosarcoma cells from staurosporine-mediated cell death.
AB  - Hyaluronidase counteracts the growth inhibitory function of transforming growth
      factor beta (TGF-beta), whereas secretion of autocrine TGF-beta and hyaluronidase
      is necessary for progression and metastasis of various cancers. Whether
      hyaluronidase and TGF-beta1 induce resistance to staurosporine in L929
      fibrosarcoma cells was investigated. When pretreated with TGF-beta1 for 1-2 h,
      L929 cells resisted staurosporine apoptosis. In contrast, without pretreatment,
      hyaluronidase protected L929 cells fromstaurosporine apoptosis. Hyaluronidase
      rapidly activated p42/44 MAPK (or ERK) in L929 cells and TGF-beta1 retarded the
      activation. Nonetheless, TGF-beta1 synergistically increased hyaluronidase
      mediated inhibition of staurosporine apoptosis. Hyaluronidase rapidly activated c
      Jun N-terminal kinase (JNK1 and JNK2) in L929 cells in 20 min. Dominant negative
      JNK1, JNK2, and JNK3 abolished the hyaluronidase inhibition of staurosporine
      apoptosis, but not the TGF-beta1 protective effect. Unlike the resistance to
      staurosporine, pretreatment of L929 cells with hyaluronidase is necessary to
      generate resistance to other anticancer drugs, including doxorubicin,
      daunorubicin, actinomycin D, and camptothecin, and the induced resistance was
      also blocked by dominant-negative JNKs. Together, hyaluronidase-mediated JNK
      activation is necessary to generate resistance to various anticancer drugs in
      L929 cells.

PMID- 11327695
TI  - Tissue-specific in vivo inhibition of DNase I gene expression by somatostatin.
AB  - Administration of somatostatin to rats induced a transient reduction of serum
      levels of deoxyribonuclease I (DNase I) activity in a dose-dependent manner,
      followed by a substantial decrease of DNase I activity in the lower gut. Activity
      in the parotid gland, liver, and kidney did not change. Real-time PCR analysis of
      the DNase I gene transcript in ileum indicated that the decrease was due to down
      regulation of gene expression. Based on these responses, rat tissues expressing
      DNase I could be classified into two types, somatostatin-sensitive and
      somatostatin-resistant, and the level of DNase I activity in the lower gut seems
      to be controlled by somatostatin.

PMID- 11327696
TI  - Cloning, mapping, genomic organization, and expression of mouse M-LP, a new
      member of the peroxisomal membrane protein Mpv17 domain family.
AB  - We have identified a mouse full-length cDNA and gene encoding a novel protein (M
      LP), based on an expressed sequence tag (EST) sequence (GenBank Accession No.
      AI482564) obtained by differential display screening of age-dependently expressed
      genes in mouse kidney. The ML-P gene is composed of three exons, ranges over 5 kb
      on mouse chromosome 16B1-B2 and is expressed as two transcripts (1455 and 3058
      bp), both of which include the same open-reading frame encoding 194 amino acids.
      M-LP is expressed mainly in kidney and spleen and shows age-dependent expression.
      M-LP has sequence homologies and membrane topologies very similar to the Mpv17
      protein, a peroxisomal protein involved in the development of early-onset
      glomerulosclerosis. Search of the protein domain family database (ProDom)
      revealed that M-LP is a new member of the Mpv17 domain family (PD008400).

PMID- 11327697
TI  - Calreticulin is directly involved in anti-alpha3 integrin antibody-mediated
      secretion and activation of matrix metalloprotease-2.
AB  - Matrix metalloprotease-2 (MMP-2) plays a pivotal role in cancer invasion and
      metastasis. Invasive human rhabdomyosarcoma cells (RD) secrete proMMP-2. We
      recently reported that anti-alpha3 integrin antibody induced the activated form
      of MMP-2 and enhanced proMMP-2 secretion by RD cells with concomitant enhancement
      of RD cell invasion. Since recent studies showed that calreticulin interacts with
      integrin alpha subunit, we hypothesized that calreticulin may be involved in
      signal transduction of anti-alpha3 integrin antibody-mediated MMP-2 secretion and
      activation. Here we demonstrate that anti-alpha3 integrin antibody induced a
      transient enhanced interaction of calreticulin with alpha3 integrin. Transfection
      of antisense oligonucleotides of calreticulin in RD cells abrogated the
      interaction between calreticulin and alpha3 integrin, and completely suppressed
      activation of MMP-2 and enhanced secretion of proMMP-2 induced by anti-alpha3
      integrin antibody. Transient overexpression of calreticulin cDNA in RD cells
      significantly increased secretion of proMMP-2. The results demonstrate for the
      first time that calreticulin is directly involved in MMP-2 secretion and
      activation.

PMID- 11327698
TI  - Activation of the IGF-II gene by HBV-X protein requires PKC and p44/p42 map
      kinase signalings.
AB  - We have recently shown that HBx protein, one of the causative agents of
      hepatocellular carcinomas, regulates Sp1 mediated transcription of insulin-like
      growth factor II promoter 4 (Lee et al. (1998) Oncogene 16, 2367-2380). Here we
      show that PKC and p44/p42MAPK signalings are required for the HBx-induced Sp1
      mediated IGF-II P4 transcriptional activity since (i) PKC activation by PMA or
      PKC expression vector increases Sp1 phosphorylation and P4 activity in HBx
      transfected HepG2 cells; (ii) PKC inhibition by PKC inhibitor Go6976 reduces Sp1
      phosphorylation, P4 activity, and IGF-II mRNA in HBx-transfected HepG2 cells; and
      (iii) the inhibition of MEK activation by U0126 reduces Sp1 phosphorylation, P4
      activity and IGF-II mRNA in HBx-transfected HepG2 cells. These results
      demonstrate that PKC and p44/p42 MAPK cascades are the essential signaling
      pathways in Sp1-mediated IGF-II gene activation by HBx.

PMID- 11327699
TI  - Constitutive expression of protective antigen gene of Bacillus anthracis in
      Escherichia coli.
AB  - The fatal bacterial infection caused by inhalation of the Bacillus anthracis
      spores results from the synthesis of protein toxins-protective antigen (PA),
      lethal factor (LF), and edema factor (EF)--by the bacterium. PA is the target
      cell binding protein and is common to the two effector molecules, LF and EF,
      which exert their toxic effects once they are translocated to the cytosol by PA.
      PA is the major component of vaccines against anthrax since it confers protective
      immunity. The large-scale production of recombinant protein-based anthrax
      vaccines requires overexpression of the PA protein. We have constitutively
      expressed the protective antigen protein in E. coli DH5alpha strain. We have
      found no increase in degradation of PA when the protein is constitutively
      expressed and no plasmid instability was observed inside the expressing cells. We
      have also scaled up the expression by bioprocess optimization using batch culture
      technique in a fermentor. The protein was purified using metal-chelate affinity
      chromatography. Approximately 125 mg of recombinant protective antigen (rPA)
      protein was obtained per liter of batch culture. It was found to be biologically
      and functionally fully active in comparison to PA protein from Bacillus
      anthracis. This is the first report of constitutive overexpression of protective
      antigen gene in E. coli.

PMID- 11327700
TI  - Type I collagen induces expression of bone morphogenetic protein receptor type
      II.
AB  - The extracellular matrix regulates many fundamental cellular processes such as
      proliferation, migration, and differentiation. Among the ECM components, type I
      collagen induces endothelial tube formation in vitro. By analysing genes
      participating in this event, the bone morphogenetic protein receptor-II (BMPR-II)
      was detected to be upregulated in cells cultured on or within fibrillar type I
      collagen. Furthermore, the basement membrane type IV collagen or amorphous type I
      collagen did not show an induction of BMPR-II. Addition of the BMPR-II specific
      ligands, BMP2 and BMP4, in the culture medium of the endothelial cells seeded on
      type I collagen increased [(3)H]-thymidine incorporation into cellular DNA,
      indicating that endothelial cells were able to form a functional receptor. In
      addition, in the chick chorioallantoic membrane (CAM), an in vivo angiogenesis
      model, BMPR-II and BMPR-I were upregulated in the growing phase and ceased in the
      mature CAM.

PMID- 11327701
TI  - Effects of diabetes and insulin on hepatic delta6 desaturase gene expression.
AB  - It has been recognized that rat liver microsomal Delta6 desaturation activity is
      defective in experimental diabetes, a fact that may be reverted by means of
      insulin treatment. In the present study, we used streptozotocin-induced diabetic
      rats in order to determine the regulatory role of insulin on the expression of
      hepatic Delta6 desaturase gene. The abundance of hepatic Delta6 desaturase mRNA
      in the diabetic rats is sevenfold lower than in the control. Insulin
      administration to diabetic rats induces Delta6 desaturase mRNA eightfold within
      24 h. The effect of insulin on the Delta6 desaturase mRNA was inhibited 70% with
      dibutyryl-cAMP and theophylline administration and 90% by cycloheximide
      administration. Therefore, our data demonstrate that the activity of hepatic
      Delta6 desaturase in response to insulin is, at least in part, regulated by
      pretranslational events that require the synthesis of an unknown protein(s).

PMID- 11327702
TI  - p73beta, a variant of p73, enhances Wnt/beta-catenin signaling in Saos-2 cells.
AB  - The Wnt/beta-catenin pathway and p53 are very common targets for genetic
      alterations in colorectal cancer, and relationships between them have been
      reported. Here, we describe the relation between Wnt/beta-catenin signaling and
      the p53-related gene p73. p73, but not p53, activated a promoter containing the
      Tcf-binding sequence in Saos-2 cells, and the degree of activation was positively
      correlated with that on a p53-responsive promoter. Moreover, p73beta enhanced
      Wnt/beta-catenin signaling synergistically with Wnt-3a or exogenously expressed
      beta-catenin, unlike p53, and the enhancement was not caused by the accumulation
      of beta-catenin. These results show that the effects of p73 on Wnt/beta-catenin
      signaling differ from those of p53.

PMID- 11327703
TI  - Significance of cathepsin B accumulation in synovial fluid of rheumatoid
      arthritis.
AB  - We measured and compared the activities of various kinds of proteinases, such as
      cysteine, serine, aspartic, and metalloproteinases, in synovial fluids of 16
      patients with rheumatoid arthritis (RA) and 18 patients with osteoarthritis (OA).
      More than 19-fold higher activity of cathepsin B and about 6-fold higher activity
      of prolylendopeptidase, compared to those of OA, were accumulated in RA fluid.
      Moreover, levels of cathepsins B and S using the corresponding sandwich enzyme
      immunoassays were statistically higher in RA fluid than those in OA. Significant
      amounts of 41-kDa and 35-kDa procathepsin L were detected in RA fluid using
      gelatin zymography, while 41-kDa enzyme alone was detected in OA. Cathepsin B in
      RA fluid could degrade collagen, and this degradation was suppressed by the
      addition of CA-074, a specific inhibitor of cathepsin B. Therefore, cathepsin B
      may participate in joint destruction of RA, and its inhibitor may be effective
      for RA care.

PMID- 11327704
TI  - Negative regulation of YY1 transcription factor on the dynamin I gene promoter.
AB  - Dynamin I is highly expressed in brain and plays a critical role in clathrin
      mediated endocytosis and synaptic vesicle recycling. To elucidate the molecular
      mechanism by which expression of dynamin I is tissue-specifically regulated, we
      previously cloned and characterized the promoter of the mouse dynamin I gene and
      suggested that there is a negative regulatory element in this promoter region. In
      the present study, we showed that YY1 binds to this negative regulatory element
      located at -111 to -107 by using the EMSA and supershift analyses. Cotransfection
      experiment using an YY1 expression vector revealed that YY1 exerts a repressive
      role on the dynamin I gene promoter activity. These results demonstrate that
      transcription factor YY1 negatively regulates dynamin I expression via binding to
      the negative regulatory element.

PMID- 11327705
TI  - 15-Deoxy-delta(12,14)-prostaglandin J(2) inhibits IL-10 and IL-12 production by
      macrophages.
AB  - 15-Deoxy-Delta(12,14)-prostaglandin J(2) (dPGJ(2)) is a metabolite of
      prostaglandin D(2), that binds to peroxisome proliferator-activated receptor
      gamma (PPARgamma). PPARgamma and prostaglandin D(2) synthase, which is required
      for dPGJ(2) synthesis, are predominantly expressed in macrophages. In contrast,
      IL-10 and IL-12 produced by macrophages stimulate Th1 and Th2 immune response,
      respectively. This study investigated the effect of dPGJ(2) on IL-10 and IL-12
      production by macrophages in response to lipopolysaccharide (LPS). Our data
      clearly demonstrated that dPGJ(2) inhibits LPS-induced IL-10 and IL-12 production
      by macrophages. A different agonist of PPARgamma, 13-hydroxyoctadecadienoic acid,
      similarly inhibited the production of IL-10 and IL-12 in response to LPS.
      Further, dPGJ(2) did not appear to act through the PGD(2) receptor. These results
      suggest that dPGJ(2) may inhibit LPS-induced IL-10 and IL-12 production by
      macrophages through PPARgamma.

PMID- 11327706
TI  - Pressure denaturation of phosphorylating glyceraldehyde-3-phosphate dehydrogenase
      from Bacillus stearothermophilus.
AB  - The effects of hydrostatic pressure on apo wild-type glyceraldehyde-3-phosphate
      dehydrogenase (wtGAPDH) from Bacillus stearothermophilus (B. stearothermophilus)
      have been studied by fluorescence spectroscopy under pressure from 0.1 to 650
      MPa. Unlike yeast GAPDH [Ruan, K. C., and Weber, G. (1989) Biochemistry 28, 2144
      2153], denaturation of the tetrameric apo wtGAPDH from B. stearothermophilus is
      likely to precede dissociation into subunits. As expected, denaturation is
      accompanied by the loss of enzymatic activity. B. stearothermophilus apo wtGAPDH
      interfaces are less pressure sensitive than apo yeast GAPDH ones, while NAD does
      not protect B. stearothermophilus wtGAPDH against denaturation by pressure. The
      pressure effects on B. stearothermophilus GAPDH whose R and Q-axis interfaces
      were destabilized by disruption of interfacial hydrogen bonds are similar to that
      of apo wtGAPDH.

PMID- 11327707
TI  - Inhibition of oligo(glutamine) precipitation by glutamine-containing peptides.
AB  - When a solution of glutamine is added to solid 1,1'-carbonyldiimidazole, a
      mixture of oligo(glutamine)s up to about the 11-mer is formed rapidly. On
      standing overnight, the solution deposits a precipitate that does not easily
      redissolve. We have studied the inhibition of this precipitation by glutamine
      containing peptides. We find that the alternating peptides (arg.gln)(4) and
      (arg.gln)(8) are efficient inhibitors of precipitation while arg(5),
      (glu.gln)(4), and a nonalternating octapeptide of the same composition as
      (arg.gln)(4) do not inhibit precipitation even though all the arg-containing
      peptides readily adsorb to oligo(glutamine) precipitates. A possible structural
      basis for this difference is discussed.

PMID- 11327708
TI  - Simultaneous occurrence of two different glyceraldehyde-3-phosphate
      dehydrogenases in heterocystous N(2)-fixing cyanobacteria.
AB  - Enzyme activity determinations and Western and Northern blot analyses have shown
      the presence of two catalytically different glyceraldehyde-3-phosphate
      dehydrogenases (GAPDH) in both vegetative cells and heterocysts of several N(2)
      fixing Anabaena strains: (a) the gap2-encoded NAD(P)-dependent GAPDH2 (EC
      1.2.1.59), the enzyme involved in the photosynthetic carbon assimilation pathway,
      which is present at higher levels in vegetative cells, and (b) the gap3-encoded
      NAD-dependent GAPDH3 (EC 1.2.1.12), presumably involved in carbohydrate anabolism
      and catabolism, which is the predominant GAPDH in heterocysts. In contrast, the
      gap1-encoded GAPDH1, which is the other NAD-dependent cyanobacterial GAPDH, is
      virtually absent in both cell types. These findings are discussed in the context
      of carbon metabolism of heterocystous N(2)-fixing cyanobacteria.

PMID- 11327709
TI  - Effects of second messengers on serine/threonine protein phosphatases in insulin
      secreting cells.
AB  - Reversible protein phosphorylation is an important and versatile mechanism by
      which cells transduce external signals into biological responses. Cellular levels
      of protein phosphorylation are determined by the balanced actions of both protein
      kinases and protein phosphatases (PPases). Compared with protein kinases,
      however, serine/threonine PPases have received less attention. In the present
      study, the effects of certain insulin secretagogues and intracellular second
      messengers, known to stimulate or inhibit insulin secretion, on the activities of
      cation-independent serine/threonine PPases were investigated in insulin-secreting
      RINm5F insulinoma cells. Raising cellular cAMP through adenylyl cyclase
      activation and phosphodiesterase inhibition in intact cells, evoked inhibitory
      effects on PPase activities. The addition of a nitric oxide donor, cyclic
      nucleotides, or proinflammatory prostaglandins to RINm5F cell homogenates at
      widely different concentrations did not affect type-1 or -2A PPase activities.
      Phosphatidyl serine seemingly activated PPase-1, while inactivating PPase-2A. A
      protein kinase C-activating phorbol ester produced the opposite results when
      added to RINm5F cell homogenates. These studies suggest that several known
      intracellular second messengers are without effect on beta-cell PPase activities.
      However, phosphatidyl serine and protein kinase C activation, whose activity is
      transiently increased by glucose, may promote insulin release through PPase
      inactivation, likely contributing to the increase in phosphorylation state that
      occurs after stimulation of insulin release. Thus, inhibition of protein
      dephosphorylation may be a novel regulatory mechanism, assisting in activation of
      the stimulus-secretion coupling in insulin-producing cells.

PMID- 11327710
TI  - Interleukin-2 binds to ganglioside GD(1b).
AB  - We have developed a solid matrix immunoassay to determine the binding of
      interleukin-2 (IL-2) to specific gangliosides. The assay establishes that
      recombinant human IL-2 binds to ganglioside GD(1b) but not to any other
      gangliosides (GM(1), GM(2), GM(3), GD(1a), GD(2), GD(3), and GT(1b)). The binding
      varies with the ratio of GD1b and IL-2. This assay enables distinguishing the
      nature of the sugar moiety of the ganglioside recognized by IL-2 and establishes
      the dosimetry of the ganglioside-IL-2 interaction. Since rIL-2 is administered
      systematically into stage IV melanoma patients, we have examined 45 tumor
      biopsies for GD(1b) content. The incidence of GD(1b) in tumor biopsies is 51%. We
      postulate that GD(1b) associated on the tumor or in the circulation of cancer
      patients may bind to rIL-2 and prevent the availability of rIL-2 to augment
      antitumor-immune response.

PMID- 11327711
TI  - Synthesis of [Cys(5)]mu-conotoxin GIIIA and its derivatives as a probe of Na(+)
      channel analysis.
AB  - The residue of Thr-5 in mu-conotoxin GIIIA (GIIIA), a receptor site I sodium
      channel blocker, was replaced with Cys. The synthesized [Cys(5)]GIIIA had a
      similar 3D structure to the native GIIIA, revealed by CD and NMR. [Cys(5)]GIIIA
      and its tagged peptides inhibited the electrically stimulated contraction of the
      rat diaphragm with relatively comparable potency to that of GIIIA. Since the
      contractile response to electrical stimuli is caused by the activation of sodium
      channels, [Cys(5)]GIIIA could be a prototype for synthesizing useful tools for
      the analysis of sodium channels. Thus, [Cys(5)]GIIIA could be a prototype for
      synthesizing useful tools for the analysis of sodium channels.

PMID- 11327712
TI  - P2y(12), a new platelet ADP receptor, target of clopidogrel.
AB  - The binding characteristics of (33)P-2MeS-ADP, a stable analogue of ADP, were
      determined on CHO cells transfected with the human P2Y(12) receptor, a novel
      purinergic receptor. These transfected CHO cells displayed a strong affinity for
      (33)P-2MeS-ADP, the binding characteristics of which corresponded in all points
      to those observed on platelets. In particular, this receptor recognised purines
      with the following order of potency: 2MeS-ADP = 2MeS-ATP > ADP = ATPgammaS = ATP
      >> UTP, a binding profile which is similar to that obtained in platelets. The
      binding of (33)P-2MeS-ADP was antagonised by pCMPS but not by MRS2179 and FSBA,
      antagonists of P2Y(1) and aggregin, respectively. Moreover, the binding of (33)P
      2MeS-ADP to these cells was strongly and irreversibly inhibited by the active
      metabolite of clopidogrel with a potency which was consistent with that observed
      for this compound on platelets. Like in platelets, 2MeS-ADP induced adenylyl
      cyclase down-regulation in these P2Y(12) transfected CHO cells, an effect which
      was absent in the corresponding non-transfected cells. As already shown in
      platelets, the active metabolite of clopidogrel antagonised 2MeS-ADP-induced
      inhibition of adenylyl cyclase on transfected cells. Our results confirm that
      P2Y(12) is the previously called "platelet P2t(AC)" receptor and show that this
      receptor is antagonised by the active metabolite of clopidogrel.

PMID- 11327714
TI  - Characterization of two promoters of the Xenopus laevis elrD gene.
AB  - The Xenopus laevis elrD gene belongs to the multigenic elav/Hu family. elrD is
      exclusively expressed in neural cells, where it could be involved in the
      posttranscriptional control of mRNAs. Here we report the isolation and
      characterization of the genomic elrD 5'-flanking region. We localized the
      transcription initiation sites and thus identified two distinct transcripts,
      elrD1 and elrD2 by 5' RACE PCR. The two transcripts derive from the use of
      alternative promoters located 915 bp apart. We show that sequences upstream of
      the elrD1 and elrD2 transcription units can direct expression of the reporter
      luciferase gene in Xenopus embryos. We also observed length variation of the ELRD
      first RNA recognition motif (RRM1).

PMID- 11327713
TI  - Regulation of mouse DNA topoisomerase IIIalpha gene expression by YY1 and USF
      transcription factors.
AB  - To investigate the mechanisms responsible for the regulation of DNA topoisomerase
      IIIalpha (TOP3alpha) gene expression, the promoter region of the mouse gene has
      been cloned and analyzed. The promoter region is moderately high in GC content
      and lacks a canonical TATA box, typical for promoters of a number of housekeeping
      genes. Transient expression of a luciferase reporter gene under the control of
      serially deleted 5'-flanking sequences demonstrated that the 34-bp region from 
      137 to -170 upstream of the transcription initiation site contains a positive
      regulatory element(s) for the efficient expression of mouse TOP3alpha gene.
      Combined analyses by gel mobility shift and supershift assays revealed that both
      YY1 and USF transcription factors were capable of binding to the 34-bp region.
      When YY1 and USF-binding elements were selectively mutated, the luciferase
      activity of the resulted constructs was greatly reduced, indicating that both YY1
      and USF function as transcriptional activators. Interestingly, YY1 and USF
      binding elements are conserved in both human and mouse TOP3alpha promoters. This
      suggests that mammalian TOP3alpha genes may possess a common mechanism of
      transcription regulation through these elements.

PMID- 11327715
TI  - Genes of SHR rats protect spontaneously diabetic BB/OK rats from diabetes:
      lessons from congenic BB.SHR rat strains.
AB  - Diabetes in BB rats share many common features with human type 1 diabetes. One of
      them is the complex and polygenic nature of disease. Analysis of cross hybrids of
      diabetic BB/OK rats and rats of different diabetes-resistant strains has
      demonstrated that beside the MHC genes, Iddm1 and the lymphopenia, Iddm2,
      additional non-MHC genes are involved in diabetes development. To study the
      importance of the non-MHC genes, Iddm4 and Iddm3, two congenic BB.SHR rat strains
      were generated by recombining a segment of the SHR chromosome 6 (Iddm4; termed
      BB.6S; 15cM) or chromosome 18 (Iddm3; termed BB.18S; 24cM) into the BB/OK
      background by serial backcrossing and marker-aided selection. The
      characterization of both congenic strains demonstrates a drastic reduction of
      diabetes frequency in comparison to the BB/OK strain (86% vs 14% and 34%). It is
      supposed that diabetes protective genes of SHR must be located on both
      chromosomal segments and that these suppress the action of the essential and most
      important genes of diabetes development in the BB/OK rat, Iddm1, and Iddm2.

PMID- 11327716
TI  - Cloning and expression of activator of CREM in testis in human testicular tissue.
AB  - Activator of cAMP-responsive element modulator (CREM) in testis (ACT) has
      recently been found in the mouse testis where it activates CREM, a transcription
      factor essential for the differentiation of spermatids into mature spermatozoa.
      The importance of CREM in human spermatogenesis prompted us to examine whether
      ACT was also present in the human testis. Western blot analysis, performed with
      an anti-mouse ACT serum, showed the presence of a single immunoreactive band of a
      size similar to murine ACT. A library screening resulted in the isolation and
      characterization of the complete cDNA which showed 88% homology with the mouse
      counterpart. The human ACT gene is composed of five coding exons, being the first
      untranslated, and the mRNA spans 835 nucleotides coding for a 284 amino acid
      protein. Expression studies by RT-PCR confirmed that ACT is present in normal
      human testis. The human ACT gene is localized on the chromosome 6.

PMID- 11327717
TI  - GATA DNA-binding protein expressed in mouse I-10 Leydig testicular tumor cells.
AB  - A nuclear extract of the mouse I-10 Leydig tumor cell line was analyzed by gel
      mobility shift assay with a combination of antibodies for various mammalian GATA
      proteins. Antibodies for GATA-4 caused a super-shift of the DNA-protein complex,
      which is formed through GATA-4 binding to an oligonucleotide with a typical GATA
      motif, while ones for GATA-1, GATA-2, GATA-3, and GATA-6 did not. These results
      indicated that I-10 cells express GATA-4 protein. Western blotting analysis of
      cellular proteins also demonstrated the presence of GATA-4 protein, the size of
      which corresponds to that of the rat orthologous protein transiently expressed in
      Cos-1 cells. A significant level of GATA-4 expression in I-10 cells would be
      advantageous for studying the roles of this protein, especially in view of
      gonadal function. We further examined the binding site preference of GATA-4
      expressed in I-10 cells. GATA-4 showed broad sequence specificity similar to GATA
      6, the order of binding core site preference being GATA > GATT > GATC, and
      adenine was favored on both sides of the core for strong binding. Thus the
      conserved zinc finger domain of GATA proteins is suggested to contribute to the
      binding sequence preference. GATA-4 expressed in I-10 cells was not susceptible
      to proteolysis coupled with cAMP signaling.

PMID- 11327718
TI  - Isolation of a family of organic anion transporters from human liver and kidney.
AB  - Five distinct organic anion transporter cDNAs, hOAT1-5, were isolated from human
      liver and kidney. hOAT1, 2, and 3 are homologous to their respective rat
      orthologues OAT1-3, whereas hOAT4 and 5 are novel clones that have not been
      identified in other species. hOAT1- and hOAT3-transfected cells showed uptake of
      p-aminohippurate and fluorescein. Cells expressing hOAT2 showed uptake of p
      aminohippurate, methotrexate, cAMP, and alpha-ketoglutarate. Northern blot
      analysis indicated differential tissue distribution for the transporter
      transcripts. These results indicate the existence of a family of organic anion
      transporting proteins in humans distinct from the oatp-like family of
      transporters.

PMID- 11327719
TI  - Enhanced infection of an X4 strain of HIV-1 due to capping and colocalization of
      CD4 and CXCR4 induced by capsianoside G, a diterpene glycoside.
AB  - We investigated whether capsianosides, diterpene glycosides, extracted from
      Capsicum plants could affect human immunodeficiency virus type 1 (HIV-1)
      infection. Significant effect on virus infection in MAGI/CCR5 cells was neither
      observed for the X4 virus by capsianosides II, XI, and A, nor for an R5 virus by
      capsianoside G. Apparent enhancement of X4 HIV-1 infection by capsianoside G was
      observed and exclusively related to the usage of the CXCR4 coreceptor. The
      capsianoside G-treated cells had no change in the expression level of CD4, CXCR4,
      and CCR5, however, colocalization and capping of CD4 and CXCR4, but not of CD4
      and CCR5 was observed. Our results suggested that capsianoside G enhanced X4
      virus infection at the level of viral penetration through the capping and
      colocalization of receptors needed for infection.

PMID- 11327721
TI  - Molecular analysis of endogenous retrovirus HRES-1: identification of frameshift
      mutations in region encoding putative 28-kDa autoantigen.
AB  - A possible involvement of HTLV-1-related endogenous sequence 1 (HRES-1) in
      autoimmune diseases has been recently reported. In primate cells, PCRs and RT
      PCRs using specific primers reveal the presence and the transcription of gag
      related sequences. However antisera generated against selected HRES-1 peptides
      failed to detect a 28-kDa protein deduced from the translated gag ORF and
      described previously. Such discordant results led us to perform DNA cloning and
      sequencing of LTR- and gag-related nucleotidic fragments. Repeated sequence
      analyses on distinct samples revealed frameshift mutations in the gag and LTR
      ORFs. Our sequence analyses detected a stop codon in the gag-related ORF, which
      is inconsistent with the expression of a 28-kDa protein. Instead of the two ORFs
      previously found, our gag-related region contained three ORFs. One of them
      demonstrated higher nucleotidic and peptidic homologies with the p19 gag of HTLV
      I. However, the molecular analyses of our new sequence did not show evidence of
      potent translation capacities.

PMID- 11327720
TI  - Expression of p40/Epstein-Barr virus nuclear antigen 1 binding protein 2.
AB  - Nucleolar protein p40/EBP2 is a proliferation-associated antigen that interacts
      with Epstein-Barr virus nuclear antigen 1 (EBNA1) to maintain the Epstein-Barr
      virus (EBV) episomes. The yeast p40/EBP2 functions in the processing of 27S-A
      into 27S-B ribosomal RNA. The present study reports high evolutionary
      conservation of the cDNA-derived amino acid sequences of p40/EBP2 from frog,
      chicken, pig, rat, mouse, bovine, and human. p40/EBP2 is ubiquitously expressed
      in human tissues. It is highly expressed in myelogenous leukemia K-562 compared
      to other cell lines tested. The human p40/EBP2 gene is located in chromosome 1
      with nine exons and eight introns. The minimal promoter region resides 300
      nucleotides upstream of a putative ATG initiation codon preceded by a pyrimidine
      rich region. These two regions contain eight Sp1 and four c-Ets-1 putative
      binding sites. Analysis of the p40/EBP2 gene and its promoter region will
      facilitate studies on the regulation of its expression in EBV-infected and
      noninfected cells.

PMID- 11327723
TI  - Synthesis of gamma-carboxylated polypeptides by alpha-cells of the pancreatic
      islets.
AB  - gamma-Carboxylated proteins were detected in normal human pancreas by
      immunohistochemistry with a monoclonal antibody (M3B) specific for gamma
      carboxyglutamyl residues. Staining appeared to be localized to the glucagon
      secreting alpha-cells in the islets of Langerhans. Consistent with this, sections
      from a glucagonoma were stained much more intensely with the M3B antibody than
      those from an insulinoma. A murine alpha-cell line (alphaTC1 Clone 9) was
      cultured and gamma-carboxylated polypeptides, identified immunologically as
      prothrombin, protein S and (tentatively) Gas6, were isolated from the
      intracellular compartment by chromatography on an M3B-coupled resin. As in liver,
      prothrombin is synthesized by alpha-cells as a gamma-carboxylated zymogen that
      can be cleaved by ecarin to form an active serine protease that is inhibited by
      hirudin. The pancreas thus appears to be a novel site of synthesis for certain
      vitamin K-dependent proteins.

PMID- 11327722
TI  - Mammalian histone deacetylase 1 protein is posttranslationally modified by
      phosphorylation.
AB  - HDAC1, a member of the histone deacetylase family, is involved in transcription
      regulation through the modification of chromatin structure. Several studies also
      implicated HDAC1 in tumorigenesis. Much attention has been concentrated on
      protein-protein interactions involving HDAC1 and the possibility that
      posttranslational modifications may occur in mammalian HDAC1 proteins has not
      been carefully and systematically investigated. In this study, we utilized in
      vivo labeling assays to demonstrate that both human and murine HDAC1 proteins are
      phosphorylated in cells. Assays using HDAC1 deletion mutants indicated that
      phosphorylation occurs in its C-terminal domain. cAMP-dependent kinase and casein
      kinase II, but not protein kinase C, cdc2, or MAP kinase, could phosphorylate
      HDAC1 in vitro, although HDAC1 contains several protein kinase C consensus sites.
      We also found that phosphorylation did not influence HDAC1 enzymatic activity
      using a human histone H4 N-terminal peptide as the substrate. Interestingly,
      HDAC1-FLAG fusion protein immunoprecipitated from transfected cells was found to
      be in association with a kinase activity, providing an in vitro assay for further
      studies of this posttranslational modification.

PMID- 11327724
TI  - Mechanisms of neuroprotection by a novel rescue factor humanin from Swedish
      mutant amyloid precursor protein.
AB  - We report a novel gene, designated Humanin (HN) cDNA, that suppresses neuronal
      cell death by K595N/M596L-APP (NL-APP), a mutant causing familial Alzheimer's
      disease (FAD), termed Swedish mutant. Transfection of neuronal cells with HN cDNA
      or treatment with the coding HN polypeptide abrogated cytotoxicity by NL-APP. HN
      suppressed neurotoxicity by Abeta1-43 in the absence of N2 supplement, but could
      not inhibit Abeta secretion from NL-APP. HN could also protect neuronal cells
      from death by NL-APP lacking the 41st and 42nd residues of the Abeta region.
      Therefore, HN suppressed neuronal cell death by NL-APP not through inhibition of
      Abeta42 secretion, but with two targets for its inhibitory action: (i) the
      intracellular toxic mechanism directly triggered by NL-APP and (ii) neurotoxicity
      by Abeta. HN will contribute to the development of curative therapy of AD,
      especially as a novel reagent that could mechanistically supplement Abeta
      production inhibitors.

PMID- 11327725
TI  - Cysteine-rich and basic domain HIV-1 Tat peptides inhibit angiogenesis and induce
      endothelial cell apoptosis.
AB  - Previous findings suggest that both the Tat polypeptide encoded by HIV-1 and Tat
      derived peptides can induce angiogenesis via activation of the KDR receptor for
      Vascular Endothelial Growth Factor (VEGF). We identified 20 amino acids and 12
      amino acid peptides corresponding to the cysteine-rich and basic domains of HIV-1
      Tat which inhibited (125)I-VEGF(165) binding to KDR and neuropilin-1 (NP-1)
      receptors in endothelial cells. Cysteine-rich and basic Tat peptides inhibited
      VEGF-induced ERK activation and mitogenesis in endothelial cells, and inhibited
      angiogenesis in vitro at concentrations similar to those which inhibited VEGF
      receptor binding. These peptides also inhibited proliferation, angiogenesis, and
      ERK activation induced by basic fibroblast growth factor with similar potency and
      efficacy. Surprisingly, we found that both cysteine-rich and basic domain Tat
      peptides strikingly induced apoptosis in endothelial cells, independent of their
      effects on VEGF and bFGF. Furthermore, we found no evidence for direct biological
      effects of recombinant Tat on VEGF receptor binding, ERK activation, endothelial
      cell survival, or mitogenesis. These findings demonstrate novel properties of Tat
      derived peptides and indicate that their major effect in endothelial cells is
      apoptosis independent of specific inhibition of VEGF receptor activation.

PMID- 11327726
TI  - The transcriptional corepressor NAB2 blocks Egr-1-mediated growth factor
      activation and angiogenesis.
AB  - Effective tissue repair results from a rapid, temporally orchestrated series of
      events. At the site of local tissue injury, the production of many growth factors
      and cytokines is, in part, stimulated by the early growth response transcription
      factors such as Egr-1. Egr-1 protein binds to a family of corepressor proteins
      called NAB which function to block or limit Egr-1 trans-activation of cognate
      target genes. NAB2 blocks Egr-1 activation of the tissue factor (TF) promoter,
      Egr-1 stimulated production of PDGF-AB, HGF, TGFbeta(1), and VEGF and the
      endogenous expression of PDGF-AB and TGFbeta(1). Expression of a wild-type NAB2
      but not a dominant negative NAB2 mutant abrogates Egr-1 driven TF promoter
      activity and tubule formation in an in vitro model of angiogenesis. These
      findings may have importance in any tissue that is subject to scarring after
      acute or chronic injury.

PMID- 11327727
TI  - Coordination chemistry of the heme in cystathionine beta-synthase: formation of
      iron(II)-isonitrile complexes.
AB  - Interaction of rat and human cystathionine-beta-synthase (CBS) with various
      potential ligands has been studied by visible and EPR spectroscopy in order to
      explore the coordination chemistry of this atypical hemeprotein. Ferric CBS did
      not react with any classical hemeprotein ligands, such as various imidazole and
      pyridine derivatives, N(-)(3) and isonitriles RNC. Ferrous CBS also failed to
      bind these nitrogenous ligands or nitrosoalkanes. However, it reacts with various
      isonitriles RNC, leading to complexes characterized by a Soret peak at 433 +/- 2
      nm. Binding of isonitriles to ferrous CBS is a relatively slow process; its rate
      markedly depends on the nature of R. It thus seems that the only exogenous
      ligands able to bind CBS iron are carbon-centered, very strong heme-Fe(II)
      ligands such as CNR, CO, and CN(-), presumably after dissociation of the CBS
      iron(II)-cysteinate bond. Isonitriles appear as interesting tools for further
      studies on the topology of CBS active site.

PMID- 11327728
TI  - Pure atmospheric pressure promotes an expression of osteopontin in human aortic
      smooth muscle cells.
AB  - Although the types of pathophysiological stimulation that initiate an
      overexpression of OPN have yet to be determined, we hypothesized that mechanical
      stress is one of the candidates which initiates OPN expression in vascular smooth
      muscle cells. Cell proliferation assay indicated that a pure atmospheric pressure
      of 160 mmHg activated cell proliferation by 11% in human aortic smooth muscle
      cells (HASMC) compared to nonpressurized controls. Immunoblot analysis probed
      with an anti-OPN antibody demonstrated a 50% increase in OPN. Dual-luciferase
      reporter assay demonstrated that OPN promoter, corresponding to the -771 through 
      1 region of OPN gene, was highly responsive to pure atmospheric pressure by ten
      times that of the control. From these observations, we concluded that pure
      atmospheric pressure directly promotes an expression of OPN in HASMC, with these
      results also suggesting that high blood pressure-mediated mechanical compression
      is involved in the process of atherosclerosis and remodeling via OPN expression
      in HASMC.

PMID- 11327729
TI  - Splenic cathepsin L is maturated from the proform by interferon-gamma after
      immunization with exogenous antigens.
AB  - The processing of foreign protein antigens into peptides requires the
      participation of various endo/lysosomal proteases in antigen-presenting cells
      (APCs). In this study, a proenzyme of cathepsin L, procathepsin L, was found to
      be present in the spleens of naive mice, as demonstrated by immunoblotting.
      Interestingly, the maturation of cathepsin L from procathepsin L was strongly
      induced when the host BALB/c mice were immunized with ovalbumin or soluble
      leishmanial antigen, despite the fact that mouse albumin, a kind of self-antigen,
      did not have such a potential. Furthermore, foreign antigens, but not self
      antigens, could increase the activity of cathepsin L, probably being mediated by
      interferon-gamma, as demonstrated by in vivo and in vitro experiments. As
      cathepsin L matured, the efficiency of antigen processing was increased in APCs.
      These results suggest that endo/lysosomal cathepsin L plays an important role in
      the immune regulation via antigen processing even in peripheral lymphoid tissues
      as well as in the thymus.

PMID- 11327730
TI  - Downregulation of the cdc2/cyclin B protein kinase activity by binding of p53 to
      p34(cdc2).
AB  - We previously found that p53 binds to the catalytic subunit of the
      p34(cdc2)/cyclin B1-kinase. In the present study we analyzed the functional
      consequences of this interaction. Binding of wild-type p53 to p34(cdc2)/cyclin B1
      results in a significant decrease of its histone H1 kinase activity. Binding of
      p53 to the kinase is a prerequisite for the inhibition because a mutant p53 which
      lacks the binding region fails to influence the enzymatic activity. Furthermore,
      by using C-terminal fragments of p53 it became obvious that also some other
      structural elements in the N-terminal region are necessary for the inhibitory
      effect. Our present study provides evidence that p53 might regulate cell-cycle
      checkpoints not only on the transcriptional level but also by binding to the cell
      cycle regulating kinase p34(cdc2).

PMID- 11327731
TI  - Novel splicing isoforms of synaptotagmin-like proteins 2 and 3: identification of
      the Slp homology domain.
AB  - Slp1-3 (synaptotagmin-like protein 1-3) is a new family of carboxyl-terminal-type
      (C-type) tandem C2 proteins that show higher sequence similarity to the C2
      domains of granuphilin-a/Slp-4 than those of other C-type tandem C2 proteins
      (e.g., synaptotagmin and the Doc2 family). However, the amino (N)-terminal
      domains of the original Slp1-3 do not contain any known protein motifs and do not
      show any sequence similarities to each other. We report four alternative splicing
      isoforms of Slp2 (designated Slp2-a-d, with the original Slp2 renamed Slp2-c) and
      two alternative splicing isoforms of Slp3 (Slp3-a and Slp3-b, the original Slp3).
      These isoforms share the same C-terminal tandem C2 structures, but their N
      terminal nucleotide sequences are completely different due to the alternate use
      of different exons. Sequence alignment of the Slp1, Slp2-a, Slp3-a, and Slp4
      amino terminal domains reveals the presence of two conserved regions among the
      Slp family, designated SHD1 (Slp homology domain 1) and SHD2, which may function
      as protein interaction sites. The SHD1 and SHD2 of Slp3-a and Slp4 are separated
      by a putative Zn(2+)-binding sequence, whereas Slp1 and Slp2 lack such Zn(2+)
      binding sequences and their SHD1 and SHD2 are linked together. In addition, we
      show that the Slp2-a/c/d mRNAs are differentially distributed in different mouse
      tissues and at different stages of development, suggesting that these transcripts
      may be regulated by different promoters.

PMID- 11327733
TI  - Susceptibility of individual cells of Saccharomyces cerevisiae to the killer
      toxin K1.
AB  - The susceptibility of sensitive yeast to killer toxins is known to depend on
      various factors, such as the selected killer toxin, the exposed yeast strain, its
      growth phase and the state of culture under given experimental conditions. The
      aim of this paper was to find whether individual cells from one culture are
      equally susceptible to the impact of the killer toxin. For this purpose the
      rhodamine B assay in a modified form was used. In order to observe the fate of
      individual cell the method of fluorescence video microscopy with a digital
      picture analysis was applied. Four selected groups of specific cells (with no,
      small, medium, and large bud, respectively) were investigated. Different
      sensitivity of Saccharomyces cerevisiae cells to the killer toxin K1 was observed
      in these cell groups. The most susceptible appeared to be the cells which were in
      S-phase (cells with the small buds); the least susceptible were the M-phase cells
      with large buds. The enhanced susceptibility in S-phase results probably from
      coincidence in higher porosity of the cell wall, accumulation of surface
      receptors, and enlarged growth activity at the surface cell structures.

PMID- 11327732
TI  - Myocardial heat shock proteins during the development of heart failure.
AB  - When cardiomyocytes are exposed to stresses, production of heat shock proteins
      (HSPs) in the cells is enhanced. Such increase in cellular HSP production is
      considered to bring about tolerance against stress-induced cell damage. The exact
      role of the cellular HSPs remains unclear. In the present study, HSPs in the
      viable left ventricular myocardium were determined during the development of
      heart failure following coronary artery ligation (CAL). The rats after CAL showed
      symptoms of chronic heart failure (CHF) at the 8th week, but not at the 1st and
      2nd weeks. Myocardial HSP27, which may bind to cytoskeletal protein, at the 1st,
      2nd, and 8th weeks after CAL was approximately 180, 160, and 125% of the control,
      respectively. Myocardial HSP60, one of mitochondrial proteins, at the 8th week
      increased to 140% of the control, whereas those at the 1st and 2nd weeks did not
      change. Myocardial HSP72, an inducible form of HSP70 family, at the 1st week
      after CAL increased to 180% of the control, whereas that at the 2nd or 8th week
      was similar to control. Myocardial heat shock constitutive protein 73 (HSC73), a
      constitutively expressed form of HSP70 family, and HSP90, which may bind to
      steroid hormone receptor and actin fiber, of CAL rats did not alter throughout
      the experiment. These findings show that diverse changes in the production of
      myocardial HSPs occur during the development of heart failure. Only the increase
      in myocardial HSP60 production was associated with the development of CHF.

PMID- 11327734
TI  - Multiple mechanisms regulate expression of low temperature responsive (LOT) genes
      in Saccharomyces cerevisiae.
AB  - Using cDNA subtraction screening, we identified five Saccharomyces cerevisiae
      genes whose expressions is up-regulated when culture temperature was down-shifted
      from 30 to 10 degrees C. Among these LOT (low temperature-responsive) genes,
      three (LOT1, LOT2, and LOT3) were identical to FBA1, RPL2B, and NOP1, encoding a
      fructose biphosphate aldolase, a ribosomal protein L2B, and a nucleolar protein
      for rRNA processing, respectively. No functions were assigned for LOT5 and LOT6,
      which are identical to YKL183w and YLR011w, respectively. Northern hybridization
      analysis revealed that these genes are not uniformly regulated in response to the
      change of growth temperature. In addition, all the LOT genes, except for
      LOT1/FBA1, were induced by a low concentration of cycloheximide. The data
      indicate that multiple mechanisms, including translational functionality may be
      involved in the regulation of LOT gene expression in yeast.

PMID- 11327735
TI  - The protein sparing function of the gut and the quality of food protein.

PMID- 11327736
TI  - Cost-benefit of home artificial nutrition regulation.

PMID- 11327737
TI  - Surgery in the elderly: the role of nutritional support.

PMID- 11327738
TI  - Survey on legislation and funding of home artificial nutrition in different
      European countries.
AB  - RATIONALE: Home Artificial Nutrition (HAN) has been an expanding area over the
      last 30 years. HAN programs have been often developed prior to the regulation by
      the National Health Systems (NHS) leading to different policies within European
      countries. The aim of this study was to compare legislation regarding HAN in
      Europe. METHOD: The Group elaborated two structured questionnaires (one for Home
      Enteral Nutrition--HEN--and one for Home Parenteral Nutrition--HPN) which were
      presented to all the members of the HAN-Working group and to the 21 ESPEN Council
      members. RESULTS: Twelve questionnaires were returned, covering for more than 375
      million inhabitants. HEN: regulated in seven countries, Italy and France being
      the first to implement reimbursement policy in 1988. Except in France, Croatia
      and the Czech Rep almost any physician can prescribe HEN. NHS totally or
      partially fund HEN, although in Austria and Israel expenses are paid for the
      patients. Provision of enteral diets and equipment varies widely within
      countries. As in HPN, most of the countries have written guidelines for health
      care workers and for patients. HPN: legislated in six countries, Denmark being
      the first in 1975. HPN programs are restricted to a few hospitals and patients
      are followed by Nutrition Support Teams (NST). The budget for HPN is 100%
      supported by NHS. Hospital pharmacy, private pharmacists and Home Care companies
      are involved in a different degree in providing and distributing solutions and
      disposables. CONCLUSIONS: HPN regulation preceded HEN regulation by 10-20 years.
      Due to this longer experience and high level of care, HPN patients are usually
      followed by NST. Despite different policies, funding is relatively uniform, NHS
      supporting most of the expenses for HAN. ESPEN could play a key role developing
      common standards for HAN all over Europe.

PMID- 11327739
TI  - Problems with solutions: drowning in the brine of an inadequate knowledge base.
AB  - BACKGROUND & AIMS: We undertook a telephone questionnaire to determine current
      fluid prescribing practices and relevant knowledge among surgical preregistration
      house officers (PRHOs) and senior house officers (SHOs) working in 25 British
      hospitals. METHODS: One hundred PRHOs were surveyed within 10 days of starting
      their first job (Group A). Fifty other PRHOs were surveyed 6-8 weeks after
      starting their first job(Group B) along with 50 surgical SHOs (Group C). Outcome
      measures included responsibility for prescribing, knowledge of the composition of
      common intravenous fluids and the principles governing their use. RESULTS: PRHOs
      were responsible for prescribing in 89% of instances. Only 56% of respondents
      stated that fluid balance charts were checked on morning ward rounds. Less than
      half were aware of the sodium content of 0.9% saline or the daily sodium
      requirement. Although potassium supplements were usually correct, 25% of
      respondents prescribed two or more litres of 0.9% saline per day, which is far in
      excess of normal requirements. Although SHOs were more confident (P<0.0001),
      there was no significant difference between the three groups for most responses.
      CONCLUSIONS: Inadequate knowledge and suboptimal prescribing of fluid and
      electrolytes is common. Undergraduate and postgraduate training in this basic
      patient management skill needs improvement, with particular emphasis on the
      practical aspects.

PMID- 11327740
TI  - Energy expenditure and intake in children with sickle cell disease during acute
      illness.
AB  - BACKGROUND: Children with sickle cell disease have frequent bouts of pain and
      infection which may increase energy expenditure, decrease energy intake and lead
      to a subsequent energy deficit. METHODS: Two groups of African-American children
      with sickle cell disease-SS genotype were enrolled in this study upon hospital
      admission for a sickle cell disease related illness: a younger (<6 years, n=14, 7
      M) and older group (> or =6 years, n=17, 8 M). Body composition and dietary
      intake were assessed, and sleeping (younger) or resting energy expenditure
      (older) were measured by indirect calorimetry at admission and one month later at
      steady state. RESULTS: Energy expenditure was not different between the two
      timepoints for younger children, but was slightly elevated at steady state (+50
      kcal/d, P=0.049) in the older group. After controlling for gender, changes in fat
      free mass and dietary intake, the significance disappeared. Energy intake in both
      groups was significantly depressed at admission compared to follow-up (P<0.01).
      CONCLUSIONS: These children and adolescents did not expend excess energy during
      their acute illness, however, an energy deficit was observed secondary to poor
      energy intake. Since 20% of patients with sickle cell disease have multiple
      hospitalizations per year, these results provide justification for the
      development and evaluation of nutrition care protocols to maintain adequate
      caloric intake during hospitalization and recovery.

PMID- 11327741
TI  - Long-chain versus medium-chain lipids in acute pancreatitis complicated by acute
      respiratory distress syndrome: effects on pulmonary hemodynamics and gas
      exchange.
AB  - BACKGROUND AND AIMS: In order to assess the effects of fat emulsions in patients
      with acute pancreatitis and acute respiratory distress syndrome (ARDS) before the
      pancreatic injury was complicated by infection, pulmonary hemodynamics and gas
      exchange were investigated during the administration of long-(LCTs) or medium
      chain triacylglycerols (MCTs). METHODS: This prospective trial included nine
      patients with acute pancreatitis and ARDS; each patient was used as his/her own
      control. In all cases, the needle aspiration culture of the pancreas was
      negative. Fat emulsion provided 50% of the energy expenditure. The patients were
      infused, in random order, with pure LCTs and a 1:1 mixture of LCTs/MCTs on days 1
      and 2, over an 8 h period. RESULTS: LCT infusion increased the mean pulmonary
      artery pressure (MPAP) from 28+/-5 to 35+/-3 mmHg, pulmonary venous admixture
      (Qva/Qt) from 26+/-5% to 36+/-5% and decreased arterial PO2(PaO2)/fractional
      inspired oxygen (FIO2) from 210+/-20 to 170+/-20 (P<0.05). The infusion of
      LCT/MCT 1:1 emulsions increased oxygen consumption (VO2) from 340+/-10 to 398+/
      15 ml/min, cardiac output (CO) from 8.8+/-0.2 to 9.5+/-0.5 L/min and CO2
      production (VCO2) from 247+/-12 to 282+/-14 mL/min (P<0.05). CONCLUSION: LCT/MCT
      1:1 mixtures are recommended in cases of acute pancreatitis and ARDS, even though
      infusion over a short period increases the metabolic demand.

PMID- 11327742
TI  - The effects of food restriction in man on hepatic metabolism of acetaminophen.
AB  - BACKGROUND: Recent reports have suggested that food deprivation may contribute to
      acetaminophen hepatotoxicity by shunting drug detoxification from the conjugative
      to the potentially toxic oxidative pathways. METHODS: This study assessed this
      concept in a prospective study of food restriction of 500 calories/day over 5
      days and also of 1000 calories/day over 13 days. Obese, otherwise normal,
      individuals received 2 g acetaminophen orally at the start and again after food
      restriction. Sequential liver tests, as well as serum and urine acetaminophen and
      its derivatives were measured. RESULTS: In both food-restricted groups there was
      no evidence of any change in the elimination or in the metabolic pattern of
      acetaminophen removal. Liver tests remained normal. The average weight loss was
      about 6 pounds. CONCLUSIONS: Our data, with this brief, but major degree of food
      restriction, and this load of acetaminophen (half-maximal daily dose), do not
      demonstrate an effect of caloric restriction on acetaminophen disposition.

PMID- 11327743
TI  - Physicochemical stability assessments of lipid emulsions of varying oil
      composition.
AB  - BACKGROUND AND AIMS: Intravenous lipid emulsions have been shown to be unstable
      when the percent fat >5 microm (PFAT >5 microm) exceeds 0.4% by weight of the
      total fat present. We investigated the physicochemical stability of a standard
      low amino acid and carbohydrate mixture containing electrolytes when combined
      with four different commercial intravenous lipid emulsions of varying oil
      composition. METHODS: The 20% (w/v) lipid emulsions studied were composed of the
      following oils (by weight): 1) 1 : 1 soybean/safflower (SS); 2) 100% soybean (S);
      3) 1 : 1 soybean/MCT (SM) and 4) 4 : 1 olive/soybean (OS). Physicochemical
      stability was assessed by light obscuration or extinction using a single-particle
      optical sensing technique to detect growth of fat globules in the large diameter
      tail (>1 microm) of the droplet size distribution and by visual analyses for
      evidence of phase separation. RESULTS: The physicochemical stability of SS and S
      based all-in-one mixtures significantly deteriorated over time when compared to
      the mixtures made from SM and OS. In addition, of the four mixtures studied that
      contained SS (n=2) and S (n=2), only one of each bag studied showed visually
      obvious destabilization by the presence of free oil from phase separation,
      despite highly abnormal changes in the globule size distribution of all four
      preparations. CONCLUSION: The results suggest that all-in-one mixtures composed
      of either soybean oil alone or in combination with safflower oil are less stable
      than those mixed with either MCT or olive oil which also contain sodium oleate
      that can act as co-emulsifying agent.

PMID- 11327744
TI  - Effects of growth hormone (rhGH) and glutamine supplemented parenteral nutrition
      on intestinal adaptation in short bowel rats.
AB  - This study was performed to compare the effects of recombinant human growth
      hormone (rhGH), glutamine (Gln) and simultaneous treatment with rhGH and Gln in
      rats subjected to 75% intestinal resection and maintained with parenteral
      nutrition (PN) for 6 days. Morphological changes including mucosal thickness,
      villus height, crypt depths and villus surface area of the residue jejunum were
      measured under a light microscope; expression of PCNA as an index of cell
      proliferation and apoptotic cells were observed using immunohistochemical
      staining; Ileal IGF-1 mRNA was determined by Northern blot analysis. The
      morphological parameters of the jejunal mucosa in rats treated with PN alone were
      only about 52-62% of those in reference group (P<0.01), this atrophy of the
      jejunal mucosa was accompanied by a 2.5-fold decrease in absolute counts of PCNA
      and a 10-fold increase in apoptotic index (P<0.01), IGF-1 mRNA transcript in
      residue ileum was decreased significantly (P<0.01). However, with rhGH or Gln,
      the mucosal architecture was improved significantly and was further improved when
      rhGH and Gln were given together, the morphological values in rats treated with
      Gln+rhGH was 79% higher than those with PN alone, and was associated with a 2
      fold increase in PCNA counts and a 4-fold decrease in apoptotic index (P<0.01),
      IGF-1 mRNA expression was 78% higher than those with PN alone (P<0.01). We
      conclude that rhGH and Gln have synergistic effects on adaptation of the
      intestinal remnant in parenterally fed, short-bowel rats. The underlying
      mechanisms are associated with increased proliferation and decreased apoptosis in
      the intestinal epithelial cells. Local intestinal production of IGF-1 plays an
      important role in adaptation of the small intestine. Our findings support the
      concept that specific gut-trophic nutrients and growth factors may be combined to
      enhance the intestinal adaptation.

PMID- 11327745
TI  - Serum levels assessment of vitamin A, E, C, B2 and carotenoids in malnourished
      and non-malnourished hospitalized elderly patients.
AB  - AIMS & METHODS: Serum levels of vitamins A, E, C, B2 and carotenoids were
      determined in protein-energy malnourished (PEM, with body mass index, BMI<18.5
      kg/m2) and non-PEM (BMI+/-18.5 kg/m2) hospitalized elderly (age > or = 65 years)
      patients, in the University Hospital of Faculty of Medicine of Ribeirao Preto,
      Sao Paulo University. RESULTS: PEM (n=21) and non-PEM (n=106) patients were
      paired for age (73.6+/-7.3 vs. 71.6+/-5.6 years) and male percentage (65.1 vs.
      52.4%). As expected, PEM elderly showed lower (P<0.05) body weight (median 43.1;
      range: 29.9-51.4 vs. 58.1; range: 45.7-143.5 kg), triceps skinfold (5.2+/-3.1 vs.
      10.1+/-4.9 mm), and mid-arm muscle circumference (20.3+/-2.5 vs. 23.1+/-3.4 cm).
      Serum albumin (4.0+/-0.9 vs. 4.1+/-0.7 g/dl) and total lymphocytes count
      (1918.3+/-919 vs. 1842.7+/-862 mm(3)) were similar, respectively, among PEM and
      non-PEM patients. The percentage of biochemical riboflavin deficiency (58.8 vs.
      56.2), low serum levels of vitamin A (28.6 vs. 29.6) and vitamin E (18.7 vs. 25)
      were similar, respectively, between PEM and non-PEM groups. The prevalence of low
      serum levels of water soluble vitamins was higher (P<0.01) in malnourished
      elderly than in the non-PEM group (ascorbic acid, 80.9 vs. 56.7%, and
      carotenoids, 14.3 vs. 3%, respectively). CONCLUSIONS: These results suggest that
      hospitalized malnourished elderly show high percentage of low water soluble
      vitamin serum levels, a phenomenon possibly linked to decreased food intake,
      especially fruits and vegetables.

PMID- 11327746
TI  - Intestinal ornithine decarboxylase in short bowel syndrome patients with oral
      diet.
AB  - The major consequence of extensive intestinal resection is loss of absorptive
      surface area, which results in malabsorption of nutrients; this condition is
      known as short-bowel syndrome (SBS). Patients with extensive small intestinal
      resection and colectomy leading to jejunostomy have the most severe SBS.
      Ornithine decarboxylase (ODC) plays a central role in cell proliferation and in
      the process of gut adaptation. Polyamine synthesis in crypt cells mediates the
      action of extracellular growth factors on DNA synthesis and mitotic activity. The
      aim of this study was to examine ODC expression and activity, diamine oxidase
      (DAO) activity and polyamine levels in the jejunal mucosa and red blood cells of
      SBS patients with a jejunostomy. The study group consisted of 6 patients (4 men
      and 2 women, mean age 55.8+/-9.8 years), who had undergone extensive small bowel
      resection and colectomy. All patients were maintained on cyclic parenteral
      nutrition and non-restricted oral nutrition. Two groups of patients operated on
      for unrelated reasons were included as the jejunum control group (n=6) and the
      ileum control group (n=13). Non statistical differences were observed in
      polyamine levels of red blood cells versus the control group (spermidine: 21.0+/
      3.6 vs. 17.7+/-1.1 and spermine: 17.1+/-8.6 vs. 13.2+/-1.6 nmol/ml RBC,
      respectively). No significant decreases in putrescine and spermidine levels were
      observed between the groups, but spermine levels in SBS jejunum were
      significantly lower than the controls (P<0.05). In SBS patients a significant
      decrease in ODC and DAO activity were observed vs jejunum. A significant decrease
      in ODC-mRNA abundance was found for the SBS patients as compared to the two
      control groups (P<0.05). These results suggest that in SBS patients with
      jejunostomy intestinal adaptation may be impaired.

PMID- 11327747
TI  - The role of free fatty acids (FFA) in the regulation of intrahepatic fluxes of
      glucose and glycogen metabolism during short-term starvation in healthy
      volunteers.

PMID- 11327748
TI  - Determination of in vivo protein synthesis in human T lymphocytes.

PMID- 11327749
TI  - Use and abuse of albumin: a survey of clinical records from an internal medicine
      ward.
AB  - BACKGROUND AND AIMS: This study was to review albumin prescriptions and
      indications in 4122 patients hospitalized in internal medicine wards in the years
      1996, 1998 and 1999, before and after the ad hoc regulations issued in 1997 by
      the Italian Ministry of Health. METHODS: In 1996 (n=63), 1998 (n=59) and 1999
      (n=55) 177 of these patients (4.3%) were given i.v. albumin. RESULTS: 161 (91%)
      of them had serum albumin values of <3.5 g/dl, while in only 36% were these
      values <2.5 g/dl. CONCLUSION: In the majority of cases albumin was erroneously
      prescribed, often to enhance diuretic efficacy or in protein energy malnutrition.
      Its prescription has not been influenced by the new recommendations.

PMID- 11327750
TI  - Enteral feeding: drug/nutrient interaction.
AB  - Enteral nutrition support via a feeding tube is the first choice for artificial
      nutrition. Most patients also require simultaneous drug therapy, with the
      potential risk for drug-nutrient interactions which may become relevant in
      clinical practice. During enteral nutrition, drug-nutrient interactions are more
      likely to occur than in patients fed orally. However, there is a lack of
      awareness about its clinical significance, which should be recognised and
      prevented in order to optimise nutritional and pharmacological therapeutic goals
      of safety and efficacy. LEARNING OBJECTIVES: To raise the awareness of potential
      drug-nutrient interactions and influence on clinical outcomes. To identify
      factors that can promote drug-nutrient interactions and contribute to nutrition
      and/or therapeutic failure. To be aware of different types of drug-nutrient
      interactions. To understand complex underlying mechanisms responsible for drug
      nutrient interactions. To learn basic rules for the administration of medications
      during tube-feeding.

PMID- 11327752
TI  - The use of expressed breast milk for the premature newborn.

PMID- 11327753
TI  - Catheter-related complications at the end of the century: is it time to change
      the technique?

PMID- 11327755
TI  - The biological functions of A-kinase anchor proteins.
AB  - cAMP-dependent protein kinase is targeted to discrete subcellular locations by a
      family of specific anchor proteins (A-kinase anchor proteins, AKAPs).
      Localization recruits protein kinase A (PKA) holoenzyme close to its
      substrate/effector proteins, directing and amplifying the biological effects of
      cAMP signaling.AKAPs include two conserved structural modules: (i) a targeting
      domain that serves as a scaffold and membrane anchor; and (ii) a tethering domain
      that interacts with PKA regulatory subunits. Alternative splicing can shuffle
      targeting and tethering domains to generate a variety of AKAPs with different
      targeting specificity. Although AKAPs have been identified on the basis of their
      interaction with PKA, they also bind other signaling molecules, mainly
      phosphatases and kinases, that regulate AKAP targeting and activate other signal
      transduction pathways. We suggest that AKAP forms a "transduceosome" by acting as
      an autonomous multivalent scaffold that assembles and integrates signals derived
      from multiple pathways. The transduceosome amplifies cAMP and other signals
      locally and, by stabilizing and reducing the basal activity of PKA, it also
      exerts long-distance effects. The AKAP transduceosome thus optimizes the
      amplitude and the signal/noise ratio of cAMP-PKA stimuli travelling from the
      membrane to the nucleus and other subcellular compartments.

PMID- 11327756
TI  - Fast selection of antibodies without antigen purification: adaptation of the
      protein fragment complementation assay to select antigen-antibody pairs.
AB  - We have adapted the protein fragment complementation assay (PCA) to the screening
      and selection of antibodies in the single-chain Fv (scFv) format. In this assay,
      two interacting proteins (target and antibody) are genetically fused to the two
      halves of the dissected enzyme dihydrofolate reductase. Binding of the two
      partners reassembles this enzyme and reconstitutes its activity, thus allowing
      growth on minimal medium. We have optimized this system with regard to linker
      length and orientation, and can reach an efficiency for antigen/antibody
      interactions similar to that with fused leucine zippers. Using several model
      antibodies specific for peptides and proteins, we show that cognate interactions
      give rise to about seven orders of magnitude more colonies than non-specific
      interactions. When transforming mixtures of plasmids encoding different antigens
      and/or antibodies, all colonies tested contained plasmids encoding cognate pairs.
      We believe that this system will be very powerful as a routine system for
      generating antibodies, especially in functional genomics, since it does not
      require purification and immobilization of the antigen. The identification of an
      antibody specific for a cDNA or EST-encoded protein will require only cloning,
      transformation and plating of bacteria.

PMID- 11327757
TI  - Evolutionary conservation of the folding nucleus.
AB  - Here, we present statistical analysis of conservation profiles in families of
      homologous sequences for nine proteins whose folding nucleus was determined by
      protein engineering methods. We show that in all but one protein (AcP) folding
      nucleus residues are significantly more conserved than the rest of the protein.
      Two aspects of our study are especially important: (i) grouping of amino acid
      residues into classes according to their physical-chemical properties and (ii)
      proper normalization of amino acid probabilities that reflects the fact that
      evolutionary pressure to conserve some amino acid types may itself affect
      concentration of various amino acid types in protein families. Neglect of any of
      those two factors may make physical and biological "signals" from conservation
      profiles disappear.

PMID- 11327758
TI  - Efficient transcriptional antitermination from the Escherichia coli cytoplasmic
      membrane.
AB  - The BglG protein is a transcriptional antiterminator acting within the beta
      glucoside operon of Escherichia coli by binding to a specific sequence motif in
      the growing mRNA. Binding of BglG prevents formation of the terminator stem-loop
      structure, thereby causing the RNA polymerase to continue transcription. Activity
      of BglG is modulated in a complex way by antagonistically acting phosphorylations
      in response to the availability of beta-glucosidic substrates and to the
      catabolic state of the cell. The enzymes responsible for these phosphorylations
      are members of the phosphoenolpyruvate:carbohydrate phosphotransferase system
      (PTS) that represents a central carbohydrate uptake and signal transduction
      system. As these enzymes are believed to all form higher-order complexes
      associated with the cytoplasmic membrane, we tested whether or not BglG would
      remain active when artificially anchored to its presumptive site of regulation,
      the inner membrane. We show that the membrane-anchored protein indeed efficiently
      catalyzes transcriptional antitermination. Moreover, the membrane-attached BglG
      remains regulated by the PTS. Thus, a membrane-bound regulatory RNA binding
      protein can potentially interact fast enough with its target within the nascent
      transcript and cause the transcriptional machinery to proceed, before
      transcriptional termination would occur. Consequently, there is no principal
      necessity for an RNA-binding transcriptional regulator like BglG to leave the
      inner membrane, a potential regulatory site, and migrate to the site of
      transcription, the nucleoid.

PMID- 11327759
TI  - The two active-site tyrosine residues of the a protein play non-equivalent roles
      during initiation of rolling circle replication of bacteriophage p2.
AB  - The A protein of bacteriophage P2 initiates rolling circle DNA replication by a
      single-stranded cut at the origin. Two well-conserved tyrosine residues,
      interspaced by three amino acid residues, are required for the cleavage-joining
      activity of the protein. The functional relationship between these tyrosine
      residues was investigated by site-directed mutagenesis. We found that the two
      tyrosine residues located in the presumed catalytic site of P2 A play non
      equivalent functional roles. Tyrosine residue 454 is superior in nicking single
      stranded DNA compared to tyrosine residue 450, while both could promote joining
      at equal efficiency. Specific peptide-oligonucleotide adducts after cleavage
      reaction and protease digestion could be observed for both tyrosine residues. We
      propose that tyrosine 454 initiates replication and that tyrosine 450 is able to
      cleave the DNA only when tyrosine 454 is covalently joined to DNA, thereby
      reinitiating replication. Also, the involvement of divalent cations in the
      catalytic activity of P2 A was investigated. While the cleavage reaction was
      strongly discriminating between different divalent cations, primarily prefering
      magnesium, the joining reaction showed the same efficiency independently of what
      divalent cation was provided. This phenomenon could reflect conformational
      changes of the protein upon binding to DNA. Finally, we found that a large part
      of the C terminus but not the N terminus is dispensable for initiation of
      replication both in vivo and in vitro.

PMID- 11327761
TI  - Functional mutagenesis of AML1/RUNX1 and PEBP2 beta/CBF beta define distinct, non
      overlapping sites for DNA recognition and heterodimerization by the Runt domain.
AB  - The Runt domain family of transcription factors play key roles in transcriptional
      regulation of definitive hematopoiesis and osteogenesis. This transcription
      factor family is characterized by a DNA-binding alpha-subunit harboring the Runt
      domain and a secondary subunit, beta, which binds to the Runt domain and enhances
      its interaction with DNA. Missense mutations in the Runt domain from either the
      blood or bone-related gene product are associated with the onset of acute human
      leukemia as well as a disease of skeletal patterning known as cleidocranial
      dysplasia. NMR "footprinting" analysis of Runt domain/beta/DNA ternary complexes
      in solution previously identified the likely residues that form the
      heterodimerization and DNA-binding surfaces of the Runt domain. Functional
      mutagenesis at 37 positions in the Runt domain or beta confirms the original
      identification of these interaction surfaces and reveals that the
      heterodimerization and DNA-binding surfaces of the Runt domain occur at distinct,
      non-overlapping sites within the domain. The analysis of an additional 21 disease
      related missense mutations identified from patients with either blood or bone
      disease demonstrates that the primary defect in these patients is a failure in
      DNA-recognition by the Runt domain. The molecular basis for the DNA-binding
      defect is analyzed in the context of the three-dimensional structure of the Runt
      domain in binary and ternary protein/DNA complexes.

PMID- 11327760
TI  - Interaction of the Neurospora crassa mitochondrial tyrosyl-tRNA synthetase (CYT
      18 protein) with the group I intron P4-P6 domain. Thermodynamic analysis and the
      role of metal ions.
AB  - The Neurospora crassa mitochondrial tyrosyl-tRNA synthetase (CYT-18 protein)
      functions in splicing group I introns by promoting the formation of the
      catalytically active structure of the intron's catalytic core. Previous studies
      suggested a model in which the protein binds first to the intron's P4-P6 domain,
      and then makes additional contacts with the P3-P9 domain to stabilize the two
      domains in the correct relative orientation to form the intron's active site.
      Here, we analyzed the interaction of CYT-18 with a small RNA (P4-P6 RNA)
      corresponding to the isolated P4-P6 domain of the N. crassa mitochondrial large
      subunit ribosomal RNA intron. RNA footprinting and modification-interference
      experiments showed that CYT-18 binds to this small RNA around the junction of the
      P4-P6 stacked helices on the side opposite the active-site cleft, as it does to
      the P4-P6 domain in the intact intron. The binding is inhibited by chemical
      modifications that disrupt base-pairing in P4, P6, and P6a, indicating that a
      partially folded structure of the P4-P6 domain is required. The temperature
      dependence of binding indicates that the interaction is driven by a favorable
      enthalpy change, but is accompanied by an unfavorable entropy change. The latter
      may reflect entropically unfavorable conformational changes or decreased
      conformational flexibility in the complex. CYT-18 binding is inhibited at > or
      =125 mM KCl, indicating a strong dependence on phosphodiester-backbone
      interactions. On the other hand, Mg(2+) is absolutely required for CYT-18
      binding, with titration experiments showing approximately 1.5 magnesium ions
      bound per complex. Metal ion-cleavage experiments identified a divalent cation
      binding site near the boundary of P6 and J6/6a, and chemical modification showed
      that Mg(2+) binding induces RNA conformational changes in this region, as well as
      elsewhere, particularly in J4/5. Together, these findings suggest a model in
      which the binding of Mg(2+) near J6/6a and possibly at one additional location in
      the P4-P6 RNA induces formation of a specific phosphodiester-backbone geometry
      that is required for CYT-18 binding. The binding of CYT-18 may then establish the
      correct structure at the junction of the P4/P6 stacked helices for assembly of
      the P3-P9 domain. The interaction of CYT-18 with the P4-P6 domain appears similar
      to the TyrRS interaction with the D-/anticodon arm stacked helices of tRNA(Tyr).

PMID- 11327762
TI  - The PDZ domain of OutC and the N-terminal region of OutD determine the secretion
      specificity of the type II out pathway of Erwinia chrysanthemi.
AB  - The plant pathogens Erwinia chrysanthemi and Erwinia carotovora secrete multiple
      exoproteins by a type II pathway, the Out system. Secretion in Erwinia is species
      specific: exoproteins of one species cannot be secreted by the other. We analysed
      the role of two components of the Out system, the bitopic inner membrane protein
      OutC and the secretin OutD, in the specific recognition of secreted proteins. We
      demonstrated that the PDZ domain of OutC determines its secretion specificity
      towards certain exoproteins. The secretin is the major determinant of specificity
      of the Out system: OutD of E. carotovora changes the secretion specificity of E.
      chrysanthemi and enables it to secrete heterologous exoproteins. Construction of
      chimeric OutD showed that the N-terminal region is the specificity domain of the
      secretin. Thus, both the PDZ domain of OutC and the N-terminal region of OutD are
      required for specific recognition of secreted proteins. Systematic analysis of
      the secretion of several exoproteins demonstrated that different exoproteins
      secreted by the Out machinery have different requirement for their presumed
      targeting signals on OutC and OutD. This strongly indicates that diverse
      exoproteins possess a variable number of targeting signals which are recognised
      by different regions of OutC and OutD.

PMID- 11327763
TI  - Flagellin polymerisation control by a cytosolic export chaperone.
AB  - Assembly of the long helical filament of the bacterial flagellum requires
      polymerisation of ca 20,000 flagellin (FliC) monomeric subunits into the growing
      structure extending from the cell surface. Here, we show that export of
      Salmonella flagellin is facilitated specifically by a cytosolic protein, FliS,
      and that FliS binds to the FliC C-terminal helical domain, which contributes to
      stabilisation of flagellin subunit interactions during polymerisation. Stable
      complexes of FliS with flagellin were assembled efficiently in vitro, apparently
      by FliS homodimers binding to FliC monomers. The data suggest that FliS acts as a
      substrate-specific chaperone, preventing premature interaction of newly
      synthesised flagellin subunits in the cytosol. Compatible with this view, FliS
      was able to prevent in vitro polymerisation of FliC into filaments.

PMID- 11327764
TI  - Locating the thapsigargin-binding site on Ca(2+)-ATPase by cryoelectron
      microscopy.
AB  - Thapsigargin (TG) is a potent inhibitor of Ca(2+)-ATPase from sarcoplasmic and
      endoplasmic reticula. Previous enzymatic studies have concluded that Ca(2+)
      ATPase is locked in a dead-end complex upon binding TG with an affinity of <1 nM
      and that this complex closely resembles the E(2) enzymatic state. We have studied
      the structural effects of TG binding by cryoelectron microscopy of tubular
      crystals, which have previously been shown to comprise Ca(2+)-ATPase molecules in
      the E(2) conformation. In particular, we have compared 3D reconstructions of
      Ca(2+)-ATPase in the absence and presence of either TG or its dansylated
      derivative. The overall molecular shape of Ca(2+)-ATPase in the reconstructions
      is very similar, demonstrating that the TG/Ca(2+)-ATPase complex does indeed
      physically resemble the E(2) conformation, in contrast to massive domain
      movements that appear to be induced by Ca(2+) binding. Difference maps reveal a
      consistent difference on the lumenal side of the membrane, which we conclude
      corresponds to the thapsigargin-binding site. Modeling the atomic structure for
      Ca(2+)-ATPase into our density maps reveals that this binding site is composed of
      the loops between transmembrane segments M3/M4 and M7/M8. Indirect effects are
      proposed to explain the effects of the S3 stalk segment on thapsigargin affinity
      as well as thapsigargin-induced changes in ATP affinity. Indeed, a second
      difference density was observed at the decavanadate-binding site within the three
      cytoplasmic domains, which we believe reflects an altered affinity as a result of
      the long-range conformational coupling that drives the reaction cycle of this
      family of ATP-dependent ion pumps.

PMID- 11327765
TI  - Ca(2+)-induced switching of troponin and tropomyosin on actin filaments as
      revealed by electron cryo-microscopy.
AB  - Muscle contraction is regulated by the intracellular Ca(2+ )concentration. In
      vertebrate striated muscle, troponin and tropomyosin on actin filaments comprise
      a Ca(2+)-sensitive switch that controls contraction. Ca(2+ )binds to troponin and
      triggers a series of changes in actin-containing filaments that lead to cyclic
      interactions with myosin that generate contraction. However, the precise location
      of troponin relative to actin and tropomyosin and how its structure changes with
      Ca(2+ )have been not determined. To understand the regulatory mechanism, we
      visualized the location of troponin by determining the three-dimensional
      structure of thin filaments from electron cryo-micrographs without imposing
      helical symmetry to approximately 35 A resolution. With Ca(2+), the globular
      domain of troponin was gourd-shaped and was located over the inner domain of
      actin. Without Ca(2+), the main body of troponin was shifted by approximately 30
      A towards the outer domain and bifurcated, with a horizontal branch (troponin
      arm) covering the N and C-terminal regions of actin. The C-terminal one-third of
      tropomyosin shifted towards the outer domain of actin by approximately 35 A
      supporting the steric blocking model, however it is surprising that the N
      terminal half of tropomyosin shifted less than approximately 12 A. Therefore
      tropomyosin shifted differentially without Ca(2+). With Ca(2+), tropomyosin was
      located entirely over the inner domain thereby allowing greater access of myosin
      for force generation. The interpretation of three-dimensional maps was
      facilitated by determining the three-dimensional positions of fluorophores
      labelled on specific sites of troponin or tropomyosin by applying probabilistic
      distance geometry to data from fluorescence resonance energy transfer
      measurements.

PMID- 11327766
TI  - Structural basis of non-specific lipid binding in maize lipid-transfer protein
      complexes revealed by high-resolution X-ray crystallography.
AB  - Non-specific lipid-transfer proteins (nsLTPs) are involved in the movement of
      phospholipids, glycolipids, fatty acids, and steroids between membranes. Several
      structures of plant nsLTPs have been determined both by X-ray crystallography and
      nuclear magnetic resonance. However, the detailed structural basis of the non
      specific binding of hydrophobic ligands by nsLTPs is still poorly understood. In
      order to gain a better understanding of the structural basis of the non-specific
      binding of hydrophobic ligands by nsLTPs and to investigate the plasticity of the
      fatty acid binding cavity in nsLTPs, seven high-resolution (between 1.3 A and 1.9
      A) crystal structures have been determined. These depict the nsLTP from maize
      seedlings in complex with an array of fatty acids.A detailed comparison of the
      structures of maize nsLTP in complex with various ligands reveals a new binding
      mode in an nsLTP-oleate complex which has not been seen before. Furthermore, in
      the caprate complex, the ligand binds to the protein cavity in two orientations
      with equal occupancy. The volume of the hydrophobic cavity in the nsLTP from
      maize shows some variation depending on the size of the bound ligands. The
      structural plasticity of the ligand binding cavity and the predominant
      involvement of non-specific van der Waals interactions with the hydrophobic tail
      of the ligands provide a structural explanation for the non-specificity of maize
      nsLTP. The hydrophobic cavity accommodates various ligands from C10 to C18. The
      C18:1 ricinoleate with its hydroxyl group hydrogen bonding to Ala68 possibly
      mimics cutin monomer binding which is of biological importance. Some of the
      myristate binding sites in human serum albumin resemble the maize nsLTP, implying
      the importance of a helical bundle in accommodating the non-specific binding of
      fatty acids.

PMID- 11327767
TI  - Electron crystallographic analysis of two-dimensional crystals of sensory
      rhodopsin II: a 6.9 A projection structure.
AB  - Sensory rhodopsins, phototaxis receptors in Haloarchaea, were purified and
      reconstituted into halobacterial lipids to form photoactive two-dimensional
      crystals. Images of vitreous ice-embedded, flattened, tubular crystals of sensory
      rhodopsin II (SRII) of Natronobacterium pharaonis were recorded using a field
      emission gun electron cryo-microscope. Fourier components for the SRII structure
      were determined either from the separated image transforms from single layers
      that formed each side of flattened tubes, or by a deconvolution procedure when
      two layers were stacked in register so that they generated a single crystal
      lattice by superposition. Most micrographs showed significant diffraction to 6.9
      A after computer processing, and the results provide the first intermediate-
      resolution information obtained for an archaeal sensory rhodopsin. The projection
      structure of SRII indicates that the helix positions match the seven-helix
      arrangement of the archaeal transport rhodopsins rather than that of the
      eukaryotic visual pigments. The structural similarity of SRII to the transport
      rhodopsins supports models in which the transport and signalling mechanisms of
      archaeal rhodopsins derive from the same retinal-driven changes in protein
      conformation.

PMID- 11327768
TI  - The X-ray crystal structure of the Trichoderma reesei family 12 endoglucanase 3,
      Cel12A, at 1.9 A resolution.
AB  - We present the three-dimensional structure of Trichoderma reesei endoglucanase 3
      (Cel12A), a small, 218 amino acid residue (24.5 kDa), neutral pI, glycoside
      hydrolase family 12 cellulase that lacks a cellulose-binding module. The
      structure has been determined using X-ray crystallography and refined to 1.9 A
      resolution. The asymmetric unit consists of six non-crystallographic symmetry
      related molecules that were exploited to improve initial multiple isomorphous
      replacement phasing, and subsequent structure refinement. The enzyme contains one
      disulfide bridge and is glycosylated at Asp164 by a single N-acetyl glucosamine
      residue. The protein has the expected fold for a glycoside hydrolase clan-C
      family 12 enzyme. It contains two beta-sheets, of six and nine strands, packed on
      top of one another, and one alpha-helix. The concave surface of the nine-stranded
      beta-sheet forms a large substrate-binding groove in which the active-site
      residues are located. In the active site, we find a carboxylic acid trio, similar
      to that of glycoside hydrolase families 7 and 16. The strictly conserved Asp99
      hydrogen bonds to the nucleophile, the invariant Glu116. The binding crevice is
      lined with both aromatic and polar amino acid side-chains which may play a role
      in substrate binding. The structure of the fungal family 12 enzyme presented here
      allows a complete structural characterization of the glycoside hydrolase-C clan.

PMID- 11327769
TI  - Conformational flexibility in T4 endonuclease VII revealed by crystallography:
      implications for substrate binding and cleavage.
AB  - The structure of the N62D mutant of the junction-resolving endonuclease VII
      (EndoVII) from phage T4 has been refined at 1.3 A, and a second wild-type crystal
      form solved and refined at 2.8 A resolution. Comparison of the mutant with the
      wild-type protein structure in two different crystal environments reveals
      considerable conformational flexibility at the dimer level affecting the
      substrate-binding cleft, the dimerization interface and the orientation of the C
      terminal domains. The opening of the DNA-binding cleft, the orientation of the C
      terminal domains relative to the central dimerization domain as well as the
      relative positioning of helices in the dimerization interface appear to be
      sensitive to the crystal packing environment. The highly unexpected rearrangement
      within the extended hydrophobic interface does change the contact surface area
      but keeps the number of hydrophobic contacts about the same and will therefore
      not require significant energy input. The conformational flexibility most likely
      is of functional significance for the broad substrate specificity of EndoVII.
      Binding of sulphate ions in the mutant structure and their positions relative to
      the active-site metal ions and residues known to be essential for catalysis
      allows us to propose a possible catalytic mechanism. A comparison with the active
      site geometries of other magnesium-dependent nucleases, among them the homing
      endonuclease I-PpoI and Serratia endonuclease, shows common features, suggesting
      related catalytic mechanisms.

PMID- 11327770
TI  - Solution structure of a C-terminal coiled-coil domain from bovine IF(1): the
      inhibitor protein of F(1) ATPase.
AB  - Bovine IF(1) is a basic, 84 amino acid residue protein that inhibits the
      hydrolytic action of the F(1)F(0) ATP synthase in mitochondria under anaerobic
      conditions. Its oligomerization state is dependent on pH. At a pH value below 6.5
      it forms an active dimer. At higher pH values, two dimers associate to form an
      inactive tetramer. Here, we present the solution structure of a C-terminal
      fragment of IF(1) (44-84) containing all five of the histidine residues present
      in the sequence. Most unusually, the molecule forms an anti-parallel coiled-coil
      in which three of the five histidine residues occupy key positions at the dimer
      interface.

PMID- 11327771
TI  - NMR characterization of clustered bistrand abasic site lesions: effect of
      orientation on their solution structure.
AB  - A unique characteristic of ionizing radiation and radiomimetic anticancer drugs
      is the induction of clustered damage: two or more DNA lesions (oxidized bases,
      abasic sites, or strand breaks) occurring in the same or different strands of the
      DNA molecule within a single turn of the helix. In spite of arising at a lower
      frequency than single lesions, clustered DNA damage represents an exotic
      challenge to the repair systems present in the cells and, in some cases, these
      lesions may escape detection and/or processing. To understand the structural
      properties of clustered DNA lesions we have prepared two oligodeoxynucleotide
      duplexes containing adjacent tetrahydrofuran residues (abasic site analogues),
      positioned one in each strand of the duplex in a 5' or 3' orientation, and
      determined their solution structure by NMR spectroscopy and molecular dynamics
      simulations. The NMR data indicate that both duplex structures are right-handed
      helices of high similarity outside the clustered damage site. The thermal
      stability of the duplexes is severely reduced by the presence of the abasic
      residues, especially in a 5' orientation where the melting temperature is 5
      degrees C lower. The structures show remarkable differences at the lesion site
      where the extrahelical location of the tetrahydrofuran residues in the (AP)(2)-5'
      staggered duplex contrasts with their smooth alignment along the sugar-phosphate
      backbone in the (AP)(2)-3'-staggered duplex.

PMID- 11327772
TI  - Solution structure of Methylophilus methylotrophus cytochrome c": insights into
      the structural basis of haem-ligand detachment.
AB  - Cytochrome c" from Methylophilus methylotrophus is a monohaem protein with 124
      amino acid residues. The iron has two histidine ligands in the oxidised form, one
      of which detaches and picks up a proton when the protein is reduced. Thus, both
      forms are paramagnetic. The structure of the oxidised form in solution,
      determined from NMR data is presented. The family of structures has an average
      backbone rmsd value of 0.53 A, and a heavy atom rmsd value of 0.95 A, within a
      target function range of 32 %. This structure is related to class I cytochromes
      with an additional helix at the N terminus. The haem-binding site occurs in a
      domain essentially lacking secondary structure motifs and the axial histidinyl
      residues were found in an unusual near perpendicular orientation. Moreover, a
      disulfide bridge is present, an uncommon structural feature among c-type
      cytochromes. The disulfide bridge, linking cysteine residues 96 and 104, forms a
      loop that confers rigidity and is essential to the detachment of the axial
      histidine (His95) as demonstrated by chemical disruption of the S-S bond. A route
      for protonation of the distal histidine involving haem propionate 17 is proposed
      and discussed in the light of available models for complex membrane proton pumps.

PMID- 11327773
TI  - Formation of the single-layer beta-sheet of Borrelia burgdorferi OspA in the
      absence of the C-terminal capping globular domain.
AB  - Borrelia outer surface protein A (OspA) contains a unique single-layer beta-sheet
      that connects N and C-terminal globular domains. This single-layer beta-sheet
      segment (beta-strands 8-10) is highly stable in solution, although it is exposed
      to the solvent on both faces of the sheet and thus it does not contain a
      hydrophobic core. Here, we tested whether interactions with the C-terminal domain
      are essential for the formation of the single-layer beta-sheet. We characterized
      the solution structure, dynamics and stability of an OspA fragment corresponding
      to beta-strands 1-12 (termed OspA[27-163]), which lacks a majority of the C
      terminal globular domain. Analyses of NMR chemical shifts and backbone nuclear
      Overhauser effect (NOE) connectivities showed that OspA[27-163] is folded except
      the 12th and final beta-strand. (1)H-(15)N heteronuclear NOE measurements and
      amide H-(2)H exchange revealed that the single-layer beta-sheet in this fragment
      is more flexible than the corresponding region in full-length OspA. Thermal
      denaturation experiments using differential scanning calorimetry and NMR
      spectroscopy revealed that the N-terminal globular domain in the fragment has a
      conformational stability similar to that of the same region in the full-length
      protein, and that the single-layer beta-sheet region also has a modest thermal
      stability. These results demonstrate that the unique single-layer beta-sheet
      retains its conformation in the absence of its interactions with the C-terminal
      domain. This fragment is significantly smaller than the full-length OspA, and
      thus it is expected to facilitate studies of the folding mechanism of this
      unusual beta-sheet structure.

PMID- 11327774
TI  - FlexE: efficient molecular docking considering protein structure variations.
AB  - Side-chain or even backbone adjustments upon docking of different ligands to the
      same protein structure, a phenomenon known as induced fit, are frequently
      observed. Sometimes point mutations within the active site influence the ligand
      binding of proteins. Furthermore, for homology derived protein structures there
      are often ambiguities in side-chain placement and uncertainties in loop modeling
      which may be critical for docking applications. Nevertheless, only very few
      molecular docking approaches have taken into account such variations in protein
      structures. We present the new software tool FlexE which addresses the problem of
      protein structure variations during docking calculations. FlexE can dock flexible
      ligands into an ensemble of protein structures which represents the flexibility,
      point mutations, or alternative models of a protein. The FlexE approach is based
      on a united protein description generated from the superimposed structures of the
      ensemble. For varying parts of the protein, discrete alternative conformations
      are explicitly taken into account, which can be combinatorially joined to create
      new valid protein structures.FlexE was evaluated using ten protein structure
      ensembles containing 105 crystal structures from the PDB and one modeled
      structure with 60 ligands in total. For 50 ligands (83 %) FlexE finds a placement
      with an RMSD to the crystal structure below 2.0 A. In all cases our results are
      of similar quality to the best solution obtained by sequentially docking the
      ligands into all protein structures (cross docking). In most cases the computing
      time is significantly lower than the accumulated run times for the single
      structures. FlexE takes about five and a half minutes on average for placing one
      ligand into the united protein description on a common workstation. The example
      of the aldose reductase demonstrates the necessity of considering protein
      structure variations for docking calculations. We docked three potent inhibitors
      into four protein structures with substantial conformational changes within the
      active site. Using only one rigid protein structure for screening would have
      missed potential inhibitors whereas all inhibitors can be docked taking all
      protein structures into account.

PMID- 11327775
TI  - A novel method of protein secondary structure prediction with high segment
      overlap measure: support vector machine approach.
AB  - We have introduced a new method of protein secondary structure prediction which
      is based on the theory of support vector machine (SVM). SVM represents a new
      approach to supervised pattern classification which has been successfully applied
      to a wide range of pattern recognition problems, including object recognition,
      speaker identification, gene function prediction with microarray expression
      profile, etc. In these cases, the performance of SVM either matches or is
      significantly better than that of traditional machine learning approaches,
      including neural networks.The first use of the SVM approach to predict protein
      secondary structure is described here. Unlike the previous studies, we first
      constructed several binary classifiers, then assembled a tertiary classifier for
      three secondary structure states (helix, sheet and coil) based on these binary
      classifiers. The SVM method achieved a good performance of segment overlap
      accuracy SOV=76.2 % through sevenfold cross validation on a database of 513 non
      homologous protein chains with multiple sequence alignments, which out-performs
      existing methods. Meanwhile three-state overall per-residue accuracy Q(3)
      achieved 73.5 %, which is at least comparable to existing single prediction
      methods. Furthermore a useful "reliability index" for the predictions was
      developed. In addition, SVM has many attractive features, including effective
      avoidance of overfitting, the ability to handle large feature spaces, information
      condensing of the given data set, etc. The SVM method is conveniently applied to
      many other pattern classification tasks in biology.

PMID- 11327776
TI  - Structure and function in bacteriorhodopsin: the role of the interhelical loops
      in the folding and stability of bacteriorhodopsin.
AB  - Bacteriorhodopsin functions as a light-driven proton pump in Halobacterium
      salinarium. The functional protein consists of an apoprotein, bacterioopsin, with
      seven transmembrane alpha helices together with a covalently bound all-trans
      retinal chromophore. In order to study the role of the interhelical loop
      conformations in the structure and function of bacteriorhodopsin, we have
      constructed bacterioopsin genes where each loop is replaced, one at a time, by a
      peptide linker consisting of Gly-Gly-Ser- repeat sequences, which are believed to
      have flexible conformations. These mutant proteins have been expressed in
      Escherichia coli, purified and reconstituted with all-trans retinal in l-alpha
      1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC)/3-(3
      cholamidopropyl)dimethylammonio-1-propane sulfonate (CHAPS)/SDS and l-alpha-1,2
      dihexanoylphosphatidylcholine (DHPC)/DMPC/SDS micelles. Wild-type-like
      chromophore formation was observed in all the mutants containing single loop
      replacements. In the BC and FG mutants, an additional chromophore band with an
      absorption band at about 480 nm was observed, which was in equilibrium with the
      550 nm, wild-type band. The position of the equilibrium depended on temperature,
      SDS and relative DMPC concentration. The proton pumping activity of all of the
      mutants was comparable to that of wild-type bR except for the BC and FG mutants,
      which had lower activity. All of the loop mutants were more sensitive to
      denaturation by SDS than the wild-type protein, except the mutant where the DE
      loop was replaced. These results suggest that a specific conformation of all the
      loops of bR, except the DE loop, contributes to bR stability and is required for
      the correct folding and function of the protein. An increase in the relative
      proportion of DHPC in DHPC/DMPC micelles, which reduces the micelle rigidity and
      alters the micelle shape, resulted in lower folding yields of all loop mutants
      except the BC and DE mutants. This effect of micelle rigidity on the bR folding
      yield correlated with a loss in stability of a partially folded, seven
      transmembrane apoprotein intermediate state in SDS/DMPC/CHAPS micelles. The
      folding yield and stability of the apoprotein intermediate state both decreased
      for the loop mutants in the order WT approximately BC approximately DE>FG>AB>EF>
      or =CD, where the EF and CD loop mutants were the least stable.

PMID- 11327777
TI  - Structure and function in bacteriorhodopsin: the effect of the interhelical loops
      on the protein folding kinetics.
AB  - The loops connecting the seven transmembrane helices of bacteriorhodopsin have
      each been replaced in turn by structureless linkers of Gly-Gly-Ser repeat
      sequences, and the effect on the protein folding kinetics has been determined. An
      SDS-denatured state of each loop mutant bacterio-opsin was folded in l-alpha-1,2
      dihexanoylphosphatidylcholine/l-alpha-1,2-dimyristoylphosphatidylcholine
      micelles, containing retinal, to give functional bacteriorhodopsin. Stopped-flow
      mixing was used to initiate the folding reaction, giving a time resolution of
      milliseconds, and changes in protein fluorescence were used to monitor folding.
      All loop mutant proteins folded according to the same reaction scheme as wild
      type protein. The folding kinetics of the AB, BC and DE loop mutants were the
      same as wild-type protein, despite the blue-shifted chromophore band of the BC
      loop mutant bR state. A partially folded apoprotein intermediate state of the AB
      loop mutant did however appear to decay in the absence of retinal. The most
      significant effects on the folding kinetics were seen for mutant protein with
      structureless linkers in place of the CD, EF and FG loops. The rate-limiting
      apoprotein folding step of the CD loop mutant was about ten times slower than
      wild-type, whilst that of the EF loop mutant was almost four times slower than
      wild-type. Wild-type behaviour was observed for the other folding and retinal
      binding events of the CD and EF loop mutant proteins. These effects of the CD and
      EF loop mutations on apoprotein folding correlate with the fact that these two
      loop mutants also have the least stable, partially folded apoprotein intermediate
      of all the loop mutants, and are the most affected by a decrease in lipid lateral
      pressure. In contrast, the FG loop mutant exhibited wild-type apoprotein folding,
      but altered covalent binding of retinal and final folding to bacteriorhodopsin.
      This correlates with the fact that the FG loop mutant bacteriorhodopsin is the
      most susceptible to denaturation by SDS of all the loop mutants, but its
      partially folded apoprotein intermediate is more stable than that of the CD and
      EF mutants. Thus the CD and EF loops may contribute to the transition state for
      the rate-limiting apoprotein folding step and the FG loop to that for final
      folding and covalent binding of retinal.

PMID- 11327778
TI  - Proline residues in transmembrane alpha helices affect the folding of
      bacteriorhodopsin.
AB  - Proline residues occur frequently in transmembrane alpha helices, which contrasts
      with their behaviour as helix-breakers in water-soluble proteins. The three
      membrane-embedded proline residues of bacteriorhodopsin have been replaced
      individually by alanine and glycine to give P50A, or P50G on helix B, P91A, or
      P91G on helix C, and P186A or P186G on helix F, and the effect on the protein
      folding kinetics has been investigated. The rate-limiting apoprotein folding
      step, which results in formation of a seven transmembrane, alpha helical state,
      was slower than wild-type protein for the Pro50 and Pro91 mutants, regardless of
      whether they were mutated to Ala or Gly. These proline residues give rise to
      several inter-helix contacts, which are therefore important in folding to the
      seven transmembrane helix state. No evidence for cis-trans isomerisations of the
      peptidyl prolyl bonds was found during this rate-limiting apoprotein folding
      step. Mutations of all three membrane-embedded proline residues affected the
      subsequent retinal binding and final folding to bacteriorhodopsin, suggesting
      that these proline residues contribute to formation of the retinal binding pocket
      within the helix bundle, again via helix/helix interactions. These results point
      to proline residues in transmembrane alpha helices being important in the folding
      of integral membrane proteins. The helix/helix interactions and hydrogen bonds
      that arise from the presence of proline residues in transmembrane alpha helices
      can affect the formation of transmembrane alpha helix bundles as well as cofactor
      binding pockets.

PMID- 11327779
TI  - Complexation precedes phosphorylation for two-component regulatory system
      FixL/FixJ of Sinorhizobium meliloti.
AB  - The FixL/FixJ two-component regulatory system of Sinorhizobium meliloti controls
      the expression of nitrogen fixation genes in response to O2. When phosphorylated,
      the transcription factor FixJ binds to the nifA and fixK promoters in S. meliloti
      and induces expression of the corresponding genes, both of which encode key
      transcription activators. Phosphorylation of FixJ has been proposed to occur via
      the following cascade. The sensor kinase FixL reacts with ATP independently of
      FixJ, transferring a phosphoryl group to one of its own histidine residues.
      Dissociation of O2 from a heme-binding PAS domain in FixL greatly accelerates the
      rate of this autophosphorylation. The phosphoryl group is rapidly transferred
      from phospho-FixL to an aspartate residue on FixJ. The resulting phospho-FixJ is
      short-lived, due to a FixL-catalyzed hydrolysis of the aspartyl phosphate. Here,
      we show that phosphorylation of FixLJ, i.e. the complex of FixL with FixJ, is at
      least tenfold faster than the phosphorylation of FixL without FixJ. We further
      show that a phospho-FixJ phosphatase, thought to reside in FixL, is absent from
      this complex. These results indicate that FixLJ reacts with ATP as a unit and
      much more efficiently than FixL alone, and that autophosphorylation and
      phosphoryl transfer do not occur independently, in sequence, but rather in a
      closely coupled processive reaction. These findings highlight the possible
      influence of synergistic interactions of the regulatory components in two
      component-system signal transduction.

PMID- 11327780
TI  - Mutational analysis of the conserved bases C1402 and A1500 in the center of the
      decoding domain of Escherichia coli 16 S rRNA reveals an important tertiary
      interaction.
AB  - Interactions within the decoding center of the 30 S ribosomal subunit have been
      investigated by constructing all 15 possible mutations at nucleotides C1402 and
      A1500 in helix 44 of 16 S rRNA. As expected, most of the mutations resulted in
      highly deleterious phenotypes, consistent with the high degree of conservation of
      this region and its functional importance. A total of seven mutants were viable
      under conditions where the mutant ribosomes comprised 100 % of the ribosomal
      pool. A suppressor mutation specific for the C1402U-A1500G mutant was isolated at
      position 1520 in helix 45 of 16 S rRNA. In addition, lack of dimethylation of
      A1518/A1519 caused by mutation of the ksgA methylase enhanced the deleterious
      effect of many of the 1402/1500 mutations. These data suggest that a higher-order
      interaction between helices 44 and 45 in 16 S rRNA is important for the proper
      functioning of the ribosome. This is consistent with the recent high-resolution
      crystal structures of the 30 S subunit, which show a tertiary interaction between
      the 1402/1500 region of helix 44 and the dimethyl A stem loop.

PMID- 11327781
TI  - Fluorescence characterization of the transcription bubble in elongation complexes
      of T7 RNA polymerase.
AB  - The various kinetic and thermodynamic models for transcription elongation all
      require an understanding of the nature of the melted bubble which moves with the
      RNA polymerase active site. Is the general nature of the bubble system-dependent
      or are there common energetic requirements which constrain a bubble in any RNA
      polymerases? T7 RNA polymerase is one of the simplest RNA polymerases and is the
      system for which we have the highest-resolution structural information. However,
      there is no high-resolution information available for a stable elongation
      complex. In order to directly map melted regions of the DNA in a functionally
      paused elongation complex, we have introduced fluorescent probes site
      specifically into the DNA. Like 2-aminopurine, which substitutes for adenine
      bases, the fluorescence intensity of the new probe, pyrrolo-dC, which substitutes
      for cytosine bases, is sensitive to its environment. Specifically, the
      fluorescence is quenched in duplex DNA relative to its fluorescence in single
      stranded DNA, such that the probe provides direct information on local melting of
      the DNA. Placement of this new probe at specific positions in the non-template
      strand shows clearly that the elongation bubble extends about eight bases
      upstream of the pause site, while 2-aminopurine probes show that the elongation
      bubble extends only about one nucleotide downstream of the last base
      incorporated. The positioning of the active site very close to the downstream
      edge of the bubble is consistent with previous studies and with similar studies
      of the promoter-bound, pre-initiation complex. The results show clearly that the
      RNA:DNA hybrid can be no more than eight nucleotides in length, and
      characterization of different paused species suggests preliminarily that these
      dimensions are not sequence or position dependent. Finally, the results confirm
      that the ternary complex is not stable with short lengths of transcript, but
      persists for a substantial time when paused in the middle or at the (runoff) end
      of duplex DNA.

PMID- 11327782
TI  - Recognition of template-primer and gapped DNA substrates by the human DNA
      polymerase beta.
AB  - Interactions between human DNA polymerase beta and the template-primer, as well
      as gapped DNA substrates, have been studied using quantitative fluorescence
      titration and analytical ultracentrifugation techniques. In solution, human pol
      beta binds template-primer DNA substrates with a stoichiometry much higher than
      predicted on the basis of the crystallographic structure of the polymerase-DNA
      complex. The obtained stoichiometries can be understood in the context of the
      polymerase affinity for the dsDNA and the two ssDNA binding modes, the (pol
      beta)(16) and (pol beta)(5) binding modes, which differ by the number of
      nucleotide residues occluded by the protein in the complex. The analysis of
      polymerase binding to different template-primer substrates has been performed
      using the statistical thermodynamic model which accounts for the existence of
      different ssDNA binding modes and has allowed us to extract intrinsic
      spectroscopic and binding parameters. The data reveal that the small 8 kDa domain
      of the enzyme can engage the dsDNA in interactions, downstream from the primer,
      in both (pol beta)(16) and (pol beta)(5) binding modes. The affinity, as well as
      the stoichiometry of human pol beta binding to the gapped DNAs is not affected by
      the decreasing size of the ssDNA gap, indicating that the enzyme recognizes the
      ssDNA gaps of different sizes with very similar efficiency. On the basis of the
      obtained results we propose a plausible model for the gapped DNA recognition by
      human pol beta. The enzyme binds the ss/dsDNA junction of the gap, using its 31
      kDa domain, with slight preference over the dsDNA. Binding only to the junction,
      but not to the dsDNA, induces an allosteric conformational transition of the
      enzyme and the entire enzyme-DNA complex which results in binding of the 8 kDa
      domain with the dsDNA. This, in turn, leads to the significant amplification of
      the enzyme affinity for the gap over the surrounding dsDNA, independent of the
      gap size. The presence of the 5'-terminal phosphate, downstream from the primer,
      has little effect on the affinity, but profoundly affects the ssDNA conformation
      in the complex. The significance of these results for the mechanistic model of
      the functioning of human pol beta is discussed.

PMID- 11327783
TI  - Epstein-Barr Virus and its glycoprotein-350 upregulate IL-6 in human B
      lymphocytes via CD21, involving activation of NF-kappaB and different signaling
      pathways.
AB  - Epstein-Barr virus (EBV) is a ubiquitous and highly immunotropic gamma
      herpesvirus that infects more than 90 % of humans worldwide. Its pathogenicity
      leads to a number of diseases including tumors that result from EBV's ability to
      readily transform B-lymphocytes and, to a lesser extent, epithelial cells. EBV
      utilizes CD21/CR2 as its receptor on B cells to initiate the infection process.
      EBV binds to CR2 through its major envelope glycoprotein-350 (gp350) and is also
      a remarkable immunomodulating agent. We had previously shown that EBV is capable
      of modulating the synthesis of a number of cytokines. We now show that while both
      purified recombinant gp350 (rgp350) and EBV upregulate IL-6 mRNA synthesis in B
      cells, EBV-induced IL-6 gene activation occurs for a significantly longer period
      of time (i.e. 12 hours for EBV as compared to 6 hours for rgp350). Moreover, the
      half-life of EBV-induced IL-6 mRNA was also significantly longer (10 hours) than
      that of mRNA induced by rgp350 (about 6 hours). Both EBV and gp350 enhance the
      binding of the NF-kappaB transcription factor, as determined by band-shift and
      augment NF-kappaB-mediated activation of a CAT reporter plasmid. Furthermore, we
      demonstrate that while the activation of IL-6 gene expression by gp350 is
      mediated primarily by the protein kinase C pathway, EBV can mediate its effects
      through multiple signaling pathways. To our knowledge this is the first report
      showing that the binding of a herpesvirus envelope glycoprotein to CR2 on human B
      cells results in the activation of the NF-kappaB transcription factor leading to
      the upregulation of IL-6 gene expression in these lymphocytes.

PMID- 11327784
TI  - Identification of a novel human islet amyloid polypeptide beta-sheet domain and
      factors influencing fibrillogenesis.
AB  - Human islet amyloid polypeptide (hIAPP) accumulates as pancreatic amyloid in type
      2 diabetes and readily forms fibrils in vitro. Investigations into the mechanism
      of hIAPP fibril formation have focused largely on residues 20 to 29, which are
      considered to comprise a primary amyloidogenic domain. In rodents, proline
      substitutions within this region and the subsequent beta-sheet disruption,
      prevents fibril formation. An additional amyloidogenic fragment within the C
      terminal sequence, residues 30 to 37, has been identified recently. We have
      extended these observations by examining a series of overlapping peptide
      fragments from the human and rodent sequences. Using protein spectroscopy
      (CD/FTIR), electron microscopy and X-ray diffraction, a previously unrecognised
      amyloidogenic domain was localised within residues 8 to 20. Synthetic peptides
      corresponding to this region exhibited a transition from random coil to beta
      sheet conformation and assembled into fibrils having a typical amyloid-like
      morphology. The comparable rat 8-20 sequence, which contains a single His18Arg
      substitution, was also capable of assembling into amyloid-like fibrils.
      Examination of peptide fragments corresponding to residues 1 to 13 revealed that
      the immediate N-terminal region is likely to have only a modulating influence on
      fibril formation or conformational conversion. The contributions of charged
      residues as they relate to the amyloid-forming 8-20 sequence were also
      investigated using IAPP fragments and by assessing the effects of pH and
      counterions. The identification of these principal amyloidogenic sequences and
      the effects of associated factors provide details on the IAPP aggregation pathway
      and structure of the peptide in its fibrillar state.

PMID- 11327785
TI  - Expression of the Fabs of human auto-antibodies in Escherichia coli: optimization
      and determination of their fine binding characteristics and cross-reactivity.
AB  - The Fabs of three human auto-antibodies (B3/33H11, anti-DNA; UK4, anti
      phospholipid) and six related hybrids have been cloned and expressed in
      Escherichia coli, and their relative binding to single-stranded or double
      stranded DNA or to cardiolipin has been assessed in the presence of modulators
      (salts and serum). We describe optimized conditions that have led to significant
      improvement in the quality and quantity of the purified auto-antibodies. Protein
      expression of the assembled and functionally active Fabs was achievable with a
      yield of up to 5 to 9 mg/l of culture. The comparative DNA/cardiolipin-binding
      analyses of the nine Fabs in the presence of modulators demonstrated that B3 and
      33H11 L chains possess both anti-DNA and anti-cardiolipin activities. This is the
      first report of the demonstration that both anti-DNA and anti-cardiolipin
      activities may lie on the same light chain of a human auto-antibody. We provide
      evidence that the auto-antibodies that appeared to be similar, in that they bound
      DNA or cardiolipin in conventional ELISA immunoassays, exhibited significant
      difference in their cross-reactivity and binding to the antigen in the presence
      of modulators. Such auto- antigen specificity and/or cross-reactivity may dictate
      the potential of an auto-antibody to cause pathogenicity and may provide an
      explanation as to why apparently similar auto-antibodies behave differently in
      vivo.

PMID- 11327786
TI  - Conformational spread in a ring of proteins: a stochastic approach to allostery.
AB  - We recently suggested that the sensitivity and range of a cluster of membrane
      receptors in bacteria would be enhanced by cooperative interactions between
      neighbouring proteins. Here, we examine the consequences of this "conformational
      spread" mechanism for an idealised one-dimensional system comprising a closed
      ring of identical allosteric protomers (protein molecules, or a group of protein
      domains operating as a unit). We show analytically and by means of Monte Carlo
      simulations that a ring of allosteric protomers can exhibit a switch-like
      response to changes in ligand concentration. We derive expressions for the
      sensitivity and cooperativity of switching and show that the maximum sensitivity
      is proportional to the number of protomers in the ring. A ring of this kind can
      reproduce the sensitivity and kinetics of the switch complex of a bacterial
      flagellar motor, for example, which is based on a ring of 34 FliM proteins. We
      also compare smaller rings of conformationally coupled protomers to classical
      allosteric proteins such as haemoglobin and show that the canonical MWC and KNF
      models arise naturally as limiting cases. Conformational spread appears to be a
      natural extension of the familiar mechanism of allostery: a physically realistic
      mechanism that should apply widely to many structures built from protein
      molecules.

PMID- 11327788
TI  - Muscle control-pain control. What exercises would you prescribe?
AB  - A very specific type of exercise has been devised which is proving to provide
      effective pain relief for chronic and recurrent back pain sufferers. The exercise
      approach focuses on retraining a precise co-contraction pattern of the deep trunk
      muscles, the transversus abdominis and lumbar multifidus. The approach is based
      on the knowledge of how muscles provide stability for the spine in normal
      situations. It has been further developed according to research evidence which
      has demonstrated dysfunction in the deep trunk muscles in patients with back
      pain. The mechanism for pain relief with this specific exercise approach is
      believed to be through enhanced stability of the lumbar spine segments.

PMID- 11327787
TI  - Single mutations at the subunit interface modulate copper reactivity in
      Photobacterium leiognathi Cu,Zn superoxide dismutase.
AB  - The functional properties and X-ray structures of five mutant forms of
      Photobacterium leiognathi Cu,Zn superoxide dismutase carrying single mutations at
      residues located at the dimer association interface have been investigated. When
      compared to the wild-type enzyme, the three-dimensional structures of the mutants
      show structural perturbations limited to the proximity of the mutation sites and
      substantial identity of active site geometry. Nonetheless, the catalytic rates of
      all mutants, measured at neutral pH and low ionic strength by pulse radiolysis,
      are higher than that of the wild-type protein. Such enzymatic activity increase
      is paralleled by enhanced active site accessibility to external chelating agents,
      which, in the mutated enzyme, remove more readily the active site copper ion. It
      is concluded that mutations at the prokaryotic Cu,Zn superoxide dismutase subunit
      interface can transduce dynamical perturbation to the active site region,
      promoting substrate active site accessibility. Such long-range intramolecular
      communication effects have not been extensively described before within the Cu,Zn
      superoxide dismutase homology family.

PMID- 11327789
TI  - Hypoalgesia post-manipulative therapy: a review of a potential neurophysiological
      mechanism.
AB  - This article provides a review of the available scientific evidence related to
      the structure and function of descending pain inhibitory systems projecting from
      the periaqueductal gray region to the spinal cord. The importance of these
      systems in the phenomenon of endogenous analgesia is discussed. The theory that
      the initial pain-relieving effect of manual therapy procedures may involve
      activation of these control systems is proposed and a series of hypotheses based
      on this theoretical concept are presented. Recent studies evaluating the effects
      of spinal mobilisation procedures are outlined and the outcomes of these studies
      are discussed in relation to theoretical role of descending pain inhibitory
      systems in manipulation-induced analgesia. Directions for further research in
      this area are considered.

PMID- 11327790
TI  - Clinical reasoning and pain.
AB  - Clinical reasoning is reviewed with respect to the historical and continuing need
      for critical inquiry skills, the hypothetico-deductive basis of sound reasoning,
      factors influencing therapists' reasoning, and ways of promoting critical yet
      creative reasoning. The importance of clinicians' organisation of biomedical and
      clinical knowledge and the inclusion of the patient in the problem solving and
      decision making processes are emphasised.

PMID- 11327791
TI  - The effect of posteroanterior mobilisation on sagittal mobility of the lumbar
      spine.
AB  - The purpose of this study was to investigate the effect of a posteroanterior
      central vertebral pressure (PA mobilisation) on sagittal mobility of the lumbar
      spine in asymptomatic subjects. On 3 separate days an experienced manipulative
      physiotherapist stood on a force platform and applied a PA mobilisation to L3
      spinous process for 2 minutes on 18 female subjects. Prior to this, subjects
      acted as their own control by lying prone for the same length of time but without
      receiving mobilisation treatment. The force platform was used to indirectly
      measure the minimum and maximum peak forces, and the frequency of oscillation of
      the applied PA mobilisation. A CA-6000 Spine Motion Analyser (SMA) was used to
      measure lumbar spine flexion and extension before and after the mobilisation and
      control treatments. Prior to the main experiment, intra-therapist reliability of
      the SMA was found to be good, with no significant difference (p > 0.05) in
      flexion or extension range of movement between 3 days of testing and root mean
      square error (RMSE) values of 7.43 degrees for flexion and 8.6 degrees for
      extension. The results indicated that a PA mobilisation with a mean maximum force
      of 92.5 N, amplitude of force oscillation of 9.6 N and a frequency of oscillation
      of 4.5 Hz had no significant affect (p > 0.05) on sagittal mobility of the lumbar
      spine in the asymptomatic subject population.

PMID- 11327792
TI  - Effects of a novel manipulative physiotherapy technique on tennis elbow: a single
      case study.
AB  - A single case study design was used to investigate the effect of a novel
      manipulative physiotherapy technique on the pain and dysfunction which
      characterises tennis elbow. The technique involves the physiotherapist sustaining
      a lateral glide of the elbow while the patient performs an activity which usually
      aggravates pain. To be judged successful, the technique should abolish pain. A
      pain visual analogue scale (VAS) and pressure algometer were used to measure
      pain. Function was measured with a grip dynamometer, function VAS and pain-free
      function questionnaire. The study involved three phases in a ABC design. They
      were a 2-week pre-treatment assessment phase, a 2-week treatment phase and a 6
      week post-treatment assessment phase. The patient received four treatment
      sessions over the treatment phase. The technique's effect was to reduce pain and
      increase function during and immediately after its application. Improvement in
      pain and function as measured by VASs was correlated (r = -0.92, p < 0.0001). The
      rate of pain reduction was greater than that for improvement in function.
      Although the single case study design limits generalisation of the results, it
      does provide evidence of the beneficial response obtained by use of this
      technique in patients affected by tennis elbow.

PMID- 11327793
TI  - Reliability and concurrent validity of two instruments for measuring cervical
      range of motion: effects of age and gender.
AB  - This study set out to determine the reliability and concurrent validity of two
      instruments for measuring cervical range of motion and, using these instruments,
      to establish age and gender effects on cervical mobility. 84 asymptomatic
      subjects were investigated for age and gender effects on cervical range of motion
      using the CROM and single inclinometer. Thirty of these subjects also took part
      in the reliability study. Intraclass correlation coefficients (ICC) for inter-
      and intra-examiner reliability of the CROM were 0.88 and 0.96
      (flexion/extension), 0.84 and 0.96 (lateral flexion) and 0.92 and 0.92 (rotation)
      respectively. Corresponding values for the inclinometer were 0.84 and 0.94; 0.82
      and 0.92; and 0.81 and 0.89. Reliability of the CROM and single inclinometer was
      thus supported. Concurrent validity of the two instruments was supported for
      flexion/extension (0.80) and lateral flexion (0.79) but not for rotation (-0.18).
      Using both measuring devices, cervical mobility decreased with age in all planes
      of motion (p < 0.0001) but was not significantly affected by gender. Based on our
      findings, reassessment of normative values of cervical range of motion is
      indicated taking age, but not gender, into account.

PMID- 11327795
TI  - Physiotherapists in the internal market.

PMID- 11327794
TI  - The development of a new form of instrument fixation for the OSI CA 6000 spine
      motion analyzer.
AB  - The CA 6000 Spine Motion Analyzer (OSI Inc., Union City, CA, USA) is an
      instrument with a computer interface which utilises electrogoniometry to provide
      an index of ranges of motion and patterns of movement for the cervical, thoracic
      or lumbar spines. A new method of securing the instrument on a subject by means
      of a skin fixation system is described. The design criteria for the new system
      are detailed along with the development stages required to attain these criteria.
      It is argued that availability of the CA 6000 with the new skin fixation system
      described, now provides a practical and ethically acceptable means of providing
      an accurate index of spinal motion and pattern of movement in both asymptomatic
      and symptomatic subjects.

PMID- 11327797
TI  - The Isolation of differentially expressed mRNA sequences by selective
      amplification via biotin and restriction-mediated enrichment.
AB  - Molecular analysis of development frequently implies the isolation and
      characterization of genes with specific spatial and temporal expression patterns.
      Several methods have been developed to identify such DNA sequences. The most
      comprehensive technique involves the genomewide probing of DNA sequence
      microarrays with mRNA sequences. However, at present this technology is limited
      to the few organisms for which the entire genome has been sequenced. Here, we
      describe a subtractive hybridization technique, called selective amplification
      via biotin and restriction-mediated enrichment (SABRE), which allows the
      selective amplification of cDNA fragments representing differentially expressed
      mRNA species. The method involves the competitive hybridization of an excess of
      driver cDNA fragments (D) to a trace of tester cDNA fragments (T), and the
      subsequent purification of tester homohybrids (in which both strands are
      contributed by the tester cDNA). After competitive hybridization, cDNA fragments
      that are more abundant in the tester than in the driver are enriched in the
      tester homohybrids. However, as the fraction of tester homohybrids is very small
      [T(2)/(D + T)(2)], their purification requires highly efficient procedures. In
      SABRE, the isolation of tester homohybrids is afforded by a combination of three
      successive steps: removal of biotinylated terminal sequences from most of the
      heterohybrids by S1 nuclease digestion, capture of biotinylated hybrids with
      streptavidin-coated paramagnetic beads, and specific release of homohybrids from
      the beads by restriction nuclease digestion. If several rounds of SABRE selection
      are performed in series, even relatively rare differentially expressed mRNA
      sequences may result in the production of predominant cDNA fragments in the final
      tester homohybrid population.

PMID- 11327798
TI  - Identification of differentially expressed genes in mouse development using
      differential display and in situ hybridization.
AB  - A common problem in developmental biology is the isolation of genes that are
      expressed differentially between two closely matched tissue populations, for
      example, between wild-type and mutant mouse embryos generated by targeted gene
      disruption. Typically, the applicable experimental methodologies are limited by
      the amount of mRNA that can be obtained for cDNA library construction and/or
      expression analysis. Differential display is a polymerase chain reaction (PCR)
      based RNA fingerprinting technique that is ideally suited for the identification
      of differentially expressed transcripts when only limiting amounts of tissue are
      available, as is frequently encountered in studies of vertebrate development.
      Here, I describe protocols for differential display using arbitrarily primed
      reverse transcription PCR and for the subsequent verification of differential
      gene expression that are adapted for molecular genetic studies of mouse
      embryogenesis. The overall strategy involves two steps: First, RNA samples
      isolated from two nearly identical populations of embryos or microdissected
      embryonic tissues are compared by differential display, and candidate
      differentially expressed transcripts are identified. Second, these candidate
      transcripts are analyzed for differential expression in vivo using nonradioactive
      whole-mount or section in situ hybridization. In principle, this strategy permits
      the efficient isolation of genes that are differentially expressed during early
      mouse embryogenesis.

PMID- 11327799
TI  - Protein recruitment systems for the analysis of protein +/- protein interactions.
AB  - The yeast Saccharomyces cerevisiae serves as an excellent genetic tool for the
      analysis of protein +/- protein interactions. The most common system, used to
      date, is the two-hybrid system. Although proven very powerful, the two-hybrid
      system exhibits several inherent problems and limitations. Recently, two
      alternative systems have been described that take advantage of the fact that
      localization of signal transduction effectors to the inner leaflet of the plasma
      membrane is absolutely necessary for yeast viability. These effectors can either
      be the Ras guanyl nucleotide exchange factor or Ras itself. The yeast strain used
      in both systems is a temperature-sensitive mutant in the yeast Ras guanyl
      nucleotide exchange factor, CDC25. Membrane localization of these effectors is
      achieved via protein +/- protein interaction. Each system can be used to test
      interaction between known protein pairs, as well as for isolation of novel
      protein interactions. Described here are the scientific and technical steps to be
      considered for both protein recruitment systems.

PMID- 11327800
TI  - Gene transfer into cultured mammalian embryos by electroporation.
AB  - To gain a better understanding of mammalian development at the molecular level,
      technology is needed that allows the transfer of exogenous genes into desired
      embryonic regions at defined stages of development. Our strategy has been to use
      electroporation (EP) of plasmid DNA following whole-embryo culture (WEC). In our
      gene transfer system, postimplantation rodent embryos are taken out of the uterus
      and a purified DNA solution of mammalian expression plasmid constructs is
      injected into the neural tube. A square-pulse current is delivered using an
      electroporator with an optimizer. Electroporated embryos are allowed to develop
      in the WEC system for 24--48 h. Within the targeted area, the proportion of
      transfected cells varied from 10% to approximately 100% depending on the test
      conditions (e.g., DNA concentration, voltage, duration of EP, and pulse number).
      The EP--WEC system has several advantages including rapid gene expression,
      minimal laboratory work, precisely targeted regions, and no risk for human
      beings. Application of the method is useful in improving our understanding of
      early neural development (E7--E12 in mice), e.g., alteration of gene function via
      ectopic expression, interference with dominant negative proteins, and fate
      mapping with marker genes. In addition, EP can complement genetic approaches such
      as the generation of knockout and transgenic mice.

PMID- 11327801
TI  - Introduction of DNA into chick embryos by in ovo electroporation.
AB  - Gene transfer by in ovo electroporation has been applied to the study of
      developmental biology, especially to central nervous system (CNS) development.
      Plasmids are injected into the neural tube of stage 10 chick embryos, and a 25-V
      25-msec square pulse is applied five times. Since DNA moves toward the anode, the
      cathode side of the neural tube is transfected, and the cathode side is used as
      the control. Expression of translation product of the introduced DNA is observed
      2 h after electroporation, peaks around 20 h after electroporation and then
      weakens. Expression is transient when plasmids are used as expression vectors,
      but they are very suitable for studying early developmental events (e.g., gene
      expression cascades or interactions). Misexpression of Pax-5 is shown as an
      example.

PMID- 11327802
TI  - Organ culture of craniofacial primordia.
AB  - Organ culture systems have proven extremely useful techniques in studies that
      investigate the process of normal and abnormal development. The explant of
      tissues into an organ culture system is one of the few techniques that maintains
      three-dimensional cellular interactions under conditions that simultaneously
      permit controlled experimental manipulation in vitro. In this article we outline
      a procedure for growing "faces" in culture. In this system, the facial primordia
      prepared from embryonic mice or chicks can be maintained in culture for up to 7-
      8 days. During this time, the facial primordia continue to grow, differentiate,
      fuse and develop into organized structures that closely resemble those observed
      in situ. The procedure is relatively simple, requiring only a stable substratum,
      culture medium, sufficient oxygenation and incubation of the organ system at 37
      degrees C. The advantages and disadvantages of the procedure are presented, along
      with detailed methods to help troubleshoot some of the common pitfalls of organ
      culture systems.

PMID- 11327803
TI  - Use of Green Fluorescent Protein in mouse embryos.
AB  - Green Fluorescent Protein (GFP) has rapidly been established as a versatile and
      powerful cell marker in many organisms. Initial problems in using it in mammalian
      cells were solved by introducing mutations to increase its solubility at higher
      temperatures, such that GFP has now been used as a reporter in both gene
      expression and cell lineage studies, and to localize proteins within mammalian
      cells. GFP has two unique advantages: (i) the protein becomes fluorescent in an
      autocatalytic reaction, so that it can be introduced into any cell type simply as
      a cDNA or mRNA, or as protein; (ii) it is "bright" enough to be visualized in
      living cells under conditions that do not cause photodamage to the cells. In this
      article we outline the ways in which we have used GFP mRNA and cDNA in our
      studies of mouse cell lineages, and to characterize the behavior of proteins
      within the embryos.

PMID- 11327804
TI  - Immunoelectron microscopy in embryos.
AB  - Immunogold labeling of proteins in sections of embryos embedded in acrylate media
      provides an important analytical tool when the resolving power of the electron
      microscope is required to define sites of protein function. The protocol
      presented here was established to analyze the role and dynamics of the activated
      protein kinase C/Rack1 regulatory system in the patterning and outgrowth of limb
      bud mesenchyme. With minor changes, especially in the composition of the fixative
      solution, the protocol should be easily adaptable for the postembedding
      immunogold labeling of any other antigen in tissues of embryos of diverse
      species. Quantification of the labeling can be achieved by using electron
      microscope systems capable of supporting digital image analysis.

PMID- 11327805
TI  - Site- and time-specific gene targeting in the mouse.
AB  - The efficient introduction of somatic mutations in a given gene, at a given time,
      in a specific cell type, will facilitate studies of gene function and the
      generation of animal models for human diseases. We have established a conditional
      site-specific recombination system in mice using a new version of the Cre/lox
      system. The Cre recombinase has been fused to a mutated ligand binding domain of
      the human estrogen receptor (ER), resulting in a tamoxifen-dependent Cre
      recombinase, Cre-ER(T), that is activated by tamoxifen, but not by estradiol.
      Transgenic mice were generated expressing Cre-ER(T) under the control of a
      cytomegalovirus promoter. Administration of tamoxifen to these transgenic mice
      induced excision of a chromosomally integrated gene flanked by loxP sites in a
      number of tissues, whereas no excision could be detected in untreated animals.
      However, the efficiency of excision varied between tissues, and the highest level
      (approximately 40%) was obtained in the skin. To determine the efficiency of
      excision mediated by Cre-ER(T) in a given cell type, Cre-ER(T)-expressing mice
      were crossed with reporter mice in which expression of Escherichia coli beta
      galactosidase can be induced through Cre-mediated recombination. The efficiency
      and kinetics of this recombination were analyzed at the cellular level in the
      epidermis of 6- to 8-week-old double transgenic mice. Site-specific excision
      occurred within a few days of tamoxifen treatment in essentially all epidermis
      cells expressing Cre-ER(T). These results indicate that cell-specific expression
      of Cre-ER(T) in transgenic mice can be used for efficient tamoxifen-dependent Cre
      mediated recombination at loci containing loxP sites, to generate site-specific
      somatic mutations in a spatiotemporally controlled manner. This conditional site
      specific recombination system should allow the analysis of knockout phenotypes
      that cannot be addressed by conventional gene targeting.

PMID- 11327806
TI  - Introducing defined chromosomal rearrangements into the mouse genome.
AB  - Chromosomal rearrangements have been instrumental in genetic studies in
      Drosophila. Visibly marked deficiencies (deletions) are used in mapping studies
      and region-specific mutagenesis screens by providing segmental haploidy required
      to uncover recessive mutations. Marked recessive lethal inversions are used as
      balancer chromosomes to maintain recessive lethal mutations and to maintain the
      integrity of mutagenized chromosomes. In mice, studies on series of radiation
      induced deletions that surround several visible mutations have yielded invaluable
      functional genomic information in the regions analyzed. However, most regions of
      the mouse genome are not accessible to such analyses due to a lack of marked
      chromosomal rearrangements. Here we describe a method to generate defined
      chromosomal rearrangements using the Cre--loxP recombination system based on a
      published strategy [R. Ramirez-Solis, P. Liu, and A. Bradley, (1995) Nature 378,
      720--724]. Various types of rearrangements, such as deletions, duplications,
      inversions, and translocations, can be engineered using this strategy.
      Furthermore, the rearrangements can be visibly marked with coat color genes,
      providing essential reagents for large-scale recessive genetic screens in the
      mouse. The ability to generate marked chromosomal rearrangements will help to
      elevate the level of manipulative mouse genetics to that of Drosophila genetics.

PMID- 11327807
TI  - Flash-induced Fourier transform infrared detection of the structural changes
      during the S-state cycle of the oxygen-evolving complex in photosystem II.
AB  - Fourier transform infrared (FTIR) difference spectra of all flash-induced S-state
      transitions of the oxygen-evolving complex were measured using photosystem II
      (PSII) core complexes of Synechococcus elongatus. The PSII core sample was given
      eight successive flashes with 1 s intervals at 10 degrees C, and FTIR difference
      spectra upon individual flashes were measured. The obtained difference spectra
      upon the first to fourth flashes showed considerably different spectral features
      from each other, whereas the fifth, sixth, seventh, and eighth flash spectra were
      similar to the first, second, third, and fourth flash spectra, respectively. The
      intensities at the wavenumbers of prominent peaks of the first and second flash
      spectra showed clear period four oscillation patterns. These oscillation patterns
      were well fitted with the Kok model with 13% misses. These results indicate that
      the first, second, third, and fourth flash spectra represent the difference
      spectra upon the S(1) --> S(2), S(2) --> S(3), S(3) --> S(0), and S(0) --> S(1)
      transitions, respectively. In these spectra, prominent bands were observed in the
      symmetric (1300-1450 cm(-)(1)) and asymmetric (1500-1600 cm(-)(1)) stretching
      regions of carboxylate groups and in the amide I region (1600-1700 cm(-)(1)).
      Comparison of the band features suggests that the drastic coordination changes of
      carboxylate groups and the protein conformational changes in the S(1) --> S(2)
      and S(2) --> S(3) transitions are reversed in the S(3) --> S(0) and S(0) --> S(1)
      transitions. The flash-induced FTIR measurements during the S-state cycle will be
      a promising method to investigate the detailed molecular mechanism of
      photosynthetic oxygen evolution.

PMID- 11327808
TI  - S-state dependent Fourier transform infrared difference spectra for the
      photosystem II oxygen evolving complex.
AB  - Vibrational spectroscopy provides a means to investigate molecular interactions
      within the active site of an enzyme. We have applied difference FTIR spectroscopy
      coupled with a flash turnover protocol of photosystem II (PSII) to study the
      oxygen evolving complex (OEC). Our data show two overlapping oscillatory patterns
      as the sample is flashed through the four-step S-state cycle that produces O(2)
      from two H(2)O molecules. The first oscillation pattern of the spectra shows a
      four-flash period four oscillation and reveals a number of new vibrational modes
      for each S-state transition, indicative of unique structural changes involved in
      the formation of each S-state. Importantly, the first and second flash difference
      spectra are reproduced in the 1800-1200 cm(-)(1) spectral region by the fifth and
      sixth flash difference spectra, respectively. The second oscillation pattern
      observed is a four-flash, period-two oscillation associated with changes
      primarily to the amide I and II modes and reports on changes in sign of these
      modes that alternate 0:0:1:1 during S-state advance. This four-flash, period-two
      oscillation undergoes sign inversion that alternates during the S(1)-to-S(2) and
      S(3)-to-S(0) transitions. Underlying this four-flash period two is a small-scale
      change in protein secondary structure in the PSII complex that is directly
      related to S-state advance. These oscillation patterns and their relationships
      with other PSII phenomena are discussed, and future work can initiate more
      detailed vibrational FTIR studies for the S-state transitions providing spectral
      assignments and further structural and mechanistic insight into the
      photosynthetic water oxidation reaction.

PMID- 11327809
TI  - Formation of a new buried charge drives a large-amplitude protein quake in
      photoreceptor activation.
AB  - Photoactive yellow protein (PYP) is a eubacterial photoreceptor and a structural
      prototype of the PAS domain superfamily of receptor and regulatory proteins. We
      investigate the activation mechanism of PYP using time-resolved Fourier transform
      infrared (FTIR) spectroscopy. Our data provide structural, kinetic, and energetic
      evidence that the putative signaling state of PYP is formed during a large
      amplitude protein quake that is driven by the formation of a new buried charge,
      COO(-) of the conserved Glu46, in a highly hydrophobic pocket at the active site.
      A protein quake is a process consisting of global conformational changes that are
      triggered and driven by a local structural "fault". We show that large, global
      structural changes take place after Glu46 ionization via intramolecular proton
      transfer to the anionic p-coumarate chromophore, and are suppressed by the
      absence of COO(-) formation in the E46Q mutant. Our results demonstrate the
      significance of buried charge formation in photoreceptor activation. This
      mechanism may serve as one of the general themes in activation of a range of
      receptor proteins. In addition, we report the results of time-resolved FTIR
      spectroscopy of PYP crystals. The direct comparison of time-resolved FTIR
      spectroscopic data of PYP in aqueous solution and in crystals reveals that the
      structure of the putative signaling state is not developed in P6(3) crystals.
      Therefore, when the structural developments during the functional process of a
      protein are experimentally determined to be very different in crystals and
      solutions, one must be cautious in drawing conclusions regarding the functional
      mechanism of proteins based on time-resolved X-ray crystallography.

PMID- 11327810
TI  - Conformations of nucleoside analogue 1-(2'-deoxy-beta-D-ribofuranosyl)-1,2,4
      triazole-3-carboxamide in different DNA sequence contexts.
AB  - The concept of using a dynamic base-pairing nucleobase as a mode for degenerate
      recognition presents a unique challenge to analysis of DNA structure. Proton and
      phosphorus NMR studies are reported for two nine-residue DNA
      oligodeoxyribonucleotides, d(CATGGGTAC).d(GTACNCATG) (1) and
      d(CATGTGTAC).(GTACNCATG) (2), which contained 1-(2'-deoxy-beta-D-ribofuranosyl)
      1,2,4-triazole-3-carboxamide (N) in the center of the helix at position 14. The
      duplexes were compared to the canonical Watson-Crick duplexes,
      d(CATGGGTAC).d(GTACCCATG) (3) and d(CATGTGTAC).d(GTACACATG) (4). Two-dimensional
      NOESY spectra of 1-4 in H(2)O and D(2)O solutions collected at 5 degrees C
      allowed assignment of the exchangeable and nonexchangeable protons for all four
      oligodeoxyribonucleotides. Thermodynamic and circular dichroism data indicated
      that 1-4 formed stable, B-form duplexes at 5 degrees C. Two-dimensional (1)H
      (31)P correlation spectra indicated that there were minor perturbations in the
      backbone only near the site of the triazole base. Strong NOESY cross-peaks were
      observed between the H5 and H1' of N14 in 1 and, unexpectedly, 2, which indicated
      that, in both duplexes, N14 was in the syn(chi)() conformation about the
      glycosidic bond. NOESY spectra of 1 and 2 recorded in 95% H(2)O, 5% D(2)O
      indicated that the imino proton of the base opposite N14, G5, or T5, formed a
      weak hydrogen bond with N14. These conformations place the polar carboxamide
      functional group in the major groove with motional averaging on the intermediate
      time scale.

PMID- 11327811
TI  - Solution structure of the Cu(I) and apo forms of the yeast metallochaperone,
      Atx1.
AB  - The (1)H NMR solution structure of the Cu(I)-bound form of Atx1, a 73-amino acid
      metallochaperone protein from the yeast Saccharomyces cerevisiae, has been
      determined. Ninety percent of the (1)H and 95% of the (15)N resonances were
      assigned, and 1184 meaningful NOEs and 42 (3)J(HNH)(alpha) and 60 (1)J(HN)
      residual dipolar couplings provided a family of structures with rmsd values to
      the mean structure of 0.37 +/- 0.07 A for the backbone and 0.83 +/- 0.08 A for
      all heavy atoms. The structure is constituted by four antiparallel beta strands
      and two alpha helices in a betaalphabetabetaalphabeta fold. Following EXAFS data
      [Pufahl, R., Singer, C. P., Peariso, K. L., Lin, S.-J., Schmidt, P. J., Fahrni,
      C. J., Cizewski Culotta, V., Penner-Hahn, J. E., and O'Halloran, T. V. (1997)
      Science 278, 853-856], a copper ion can be placed between two sulfur atoms of
      Cys15 and Cys18. The structure of the reduced apo form has also been determined
      with similar resolution using 1252 meaningful NOEs (rmsd values for the family to
      the mean structure are 0.67 +/- 0.12 A for the backbone and 1.00 +/- 0.12 A for
      all heavy atoms). Comparison of the Cu(I) and apo conformations of the protein
      reveals that the Cu(I) binding cysteines move from a buried site in the bound
      metal form to a solvent-exposed conformation on the surface of the protein after
      copper release. Furthermore, copper release leads to a less helical character in
      the metal binding site. Comparison with the Hg(II)-Atx1 solid-state structure
      [Rosenzweig, A. C., Huffman, D. L., Hou, M. Y., Wernimont, A. K., Pufahl, R. A.,
      and O'Halloran, T. V. (1999) Structure 7, 605-617] provides insights into the
      copper transfer mechanism, and a pivotal role for Lys65 in the metal capture and
      release process is proposed.

PMID- 11327812
TI  - Mechanistic features and structure of the nitrogenase alpha-Gln195 MoFe protein.
AB  - EPR signals observed under CO and C(2)H(2) during nitrogenase turnover were
      investigated for the alpha-Gln(195) MoFe protein, an altered form for which the
      alpha-His(195) residue has been substituted by glutamine. Under CO, samples show
      S = 1/2 hi- and lo-CO EPR signals identical to those recognized for the wild-type
      protein, whereas the S = 3/2 signals generated under high CO/high flux conditions
      differ. Previous work has revealed that the EPR spectrum generated under C(2)H(2)
      exhibits a signal (S(EPR1)) originating from the FeMo-cofactor having two or more
      bound C(2)H(2) adducts and a second signal (S(EPR2)) arising from a radical
      species [Sorlie, M., Christiansen, J., Dean, D. R., and Hales, B. J. (1999) J.
      Am. Chem. Soc. 121, 9457-9458]. Pressure-dependent studies show that the
      intensity of these signals has a sigmoidal dependency at low pressures and
      maximized at 0.1 atm C(2)H(2) with a subsequent decrease in steady-state
      intensity at higher pressures. Analogous signals are not recognized for the wild
      type MoFe protein. Analysis of the principal g-factors of S(EPR2) suggests that
      it either represents an unusual metal cluster or is a carboxylate centered
      radical possibly originating from homocitrate. Both S(EPR1) and S(EPR2) exhibit
      similar relaxation properties that are atypical for S = 1/2 signals originating
      from Fe-S clusters or radicals and indicate a coupled relaxation pathway. The
      alpha-Gln(195) MoFe protein also exhibits these signals when incubated under
      turnover conditions in the presence of C(2)H(4). Under these conditions,
      additional inflections in the g 4-6 region assigned to ground-state transitions
      of an S = 3/2 spin system are also recognized and assigned to turnover states of
      the MoFe protein without C(2)H(4) bound. The structure of alpha-Gln(195) was
      crystallographically determined and found to be virtually identical to that of
      the wild-type MoFe protein except for replacement of an NuH-S hydrogen bond
      interaction between FeMo-cofactor and the imidazole side chain of alpha-His(195)
      by an analogous interaction involving Gln.

PMID- 11327813
TI  - Asparagine 23 and aspartate 305 are essential residues in the active site of UDP
      N-acetylglucosamine enolpyruvyl transferase from Enterobacter cloacae.
AB  - UDP-N-acetylglucosamine enolpyruvyl transferase (MurA) catalyzes the transfer of
      the intact enolpyruvyl moiety of phosphoenolpyruvate (PEP) to the 3'-hydroxyl
      group of UDP-N-acetylglucosamine (UDPNAG). This reaction constitutes the first
      committed step in the biosynthesis of the bacterial cell wall component
      peptidoglycan (murein). The transfer reaction involves the nucleophilic attack of
      the 3'-hydroxyl group of UDPNAG at the C-2 of PEP. The three-dimensional
      structure of MurA complexed with UDPNAG revealed an aspartate residue (D305 in
      the En. cloacae sequence) close to the 3'-hydroxyl group of UDPNAG, suggesting
      that it may act as an acid-base catalyst in the active center of the enzyme. In
      addition to aspartate 305, asparagine 23 also interacts with the 3'-hydroxyl
      group; however, its role in catalysis or binding of the UDPNAG substrate is
      unclear. To gain information on the role of these two amino acids in the MurA
      catalyzed reaction we have exchanged D305 for alanine, cysteine, histidine, and
      glutamate, and N23 for alanine and serine using site-directed mutagenesis. While
      the D305 alanine, cysteine, and histidine mutant proteins do not have detectable
      enzymatic activity, the D305E mutant protein exhibits a low residual activity
      (ca. 0.1% of the wild-type enzyme). Unlike with wild-type MurA, no exothermic
      signal was obtained when the D305A and -E mutant proteins were titrated with
      UDPNAG, demonstrating that the affinity of the sugar nucleotide substrate is
      reduced as a result of the amino acid exchange. The reduced affinity to UDPNAG
      leads to a lower propensity of C115 to form either the O-phosphothioketal with
      PEP or the thioether with the antibiotic fosfomycin. These findings emphasize the
      dual role of D305 as a general base and an essential binding partner to UDPNAG in
      the active site of MurA. Similarly, the two N23 mutant proteins showed a much
      lower catalytic activity although binding of UDPNAG was not as much affected as
      in the case of the D305 mutant proteins. This result indicates that this amino
      acid residue is mainly involved in stabilization of transition states.

PMID- 11327815
TI  - Crystal structure of maleylacetoacetate isomerase/glutathione transferase zeta
      reveals the molecular basis for its remarkable catalytic promiscuity.
AB  - Maleylacetoacetate isomerase (MAAI), a key enzyme in the metabolic degradation of
      phenylalanine and tyrosine, catalyzes the glutathione-dependent isomerization of
      maleylacetoacetate to fumarylacetoacetate. Deficiencies in enzymes along the
      degradation pathway lead to serious diseases including phenylketonuria,
      alkaptonuria, and the fatal disease, hereditary tyrosinemia type I. The structure
      of MAAI might prove useful in the design of inhibitors that could be used in the
      clinical management of the latter disease. Here we report the crystal structure
      of human MAAI at 1.9 A resolution in complex with glutathione and a sulfate ion
      which mimics substrate binding. The enzyme has previously been shown to belong to
      the zeta class of the glutathione S-transferase (GST) superfamily based on
      limited sequence similarity. The structure of MAAI shows that it does adopt the
      GST canonical fold but with a number of functionally important differences. The
      structure provides insights into the molecular bases of the remarkable array of
      different reactions the enzyme is capable of performing including isomerization,
      oxygenation, dehalogenation, peroxidation, and transferase activity.

PMID- 11327814
TI  - Crystal structure of rabbit phosphoglucose isomerase complexed with 5-phospho-D
      arabinonate identifies the role of Glu357 in catalysis.
AB  - Phosphoglucose isomerase (PGI; E.C. 5.3.1.9) catalyzes the second step in
      glycolysis, the interconversion of D-glucose-6-phosphate and D-fructose-6
      phosphate. We determined the X-ray crystal structure of rabbit PGI complexed with
      a competitive inhibitor of isomerase activity, 5-phospho-D-arabinonate (5PAA), at
      1.9 A resolution. 5PAA is a better mimic of the proposed cis-enediol(ate)
      intermediate than 6-phospho-D-gluconate, which was used in a previously reported
      crystal structure of rabbit PGI. The orientation of 5PAA bound in the enzyme
      active site predicts that active site residue Glu357 is the residue that
      transfers a proton between C2 and C1 of the proposed cis-enediol(ate)
      intermediate. Amino acid residues Arg272 and Lys210 are predicted to be involved
      in stabilizing the negative charge of the intermediate.

PMID- 11327816
TI  - Adenosine 5'-0-[S-(4-succinimidyl-benzophenone)thiophosphate]: a new
      photoaffinity label of the allosteric ADP site of bovine liver glutamate
      dehydrogenase.
AB  - By reaction of adenosine 5'-monothiophosphate with benzophenone-4-maleimide, we
      synthesized adenosine 5'-O-[S-(4-succinimidyl-benzophenone)thiophosphate] (AMPS
      Succ-BP) as a photoreactive ADP analogue. Bovine liver glutamate dehydrogenase is
      known to be allosterically activated by ADP, but the ADP site has not been
      located in the crystal structure of the hexameric enzyme [Peterson, P. E., and
      Smith, T. J. (1999) Structure 7, 769-782]. In the dark, AMPS-Succ-BP reversibly
      activates GDH. Irradiation of the complex of glutamate dehydrogenase and AMPS
      Succ-BP at lambda >300 nm causes a time-dependent, irreversible 2-fold activation
      of the enzyme. The k(obs) for photoactivation shows nonlinear dependence on the
      concentration of AMPS-Succ-BP, with K(R) = 4.9 microM and k(max) = 0.076 min(
      )(1). The k(obs) for photoreaction by 20 microM AMPS-Succ-BP is decreased 10-fold
      by 200 microM ADP, but is reduced less than 2-fold by NAD, NADH, GTP, or alpha
      ketoglutarate. Modified enzyme is no longer activated by ADP, but is still
      inhibited by GTP and high concentrations of NADH. These results indicate that
      reaction of AMPS-Succ-BP occurs within the ADP site. The enzyme incorporates up
      to 0.5 mol of [(3)H]AMPS-Succ-BP/mol of enzyme subunit or 3 mol of reagent/mol of
      hexamer. The peptide Lys(488)-Glu(495) has been identified as the only reaction
      target, and the data suggest that Arg(491) is the modified amino acid. Arg(491)
      (in the C-terminal helix close to the GTP #2 binding domain of GDH) is thus
      considered to be at or near the enzyme's allosteric ADP site. On the basis of
      these results, the AMPS-Succ-BP was positioned within the crystal structure of
      glutamate dehydrogenase, where it should also mark the ADP binding site of the
      enzyme.

PMID- 11327817
TI  - A refined model of the chlorosomal antennae of the green bacterium Chlorobium
      tepidum from proton chemical shift constraints obtained with high-field 2-D and 3
      D MAS NMR dipolar correlation spectroscopy.
AB  - Heteronuclear 2-D and 3-D magic-angle spinning NMR dipolar correlation
      spectroscopy was applied to determine solid-state (1)H shifts for aggregated
      bacteriochlorophyll c (BChl c) in uniformly (13)C-enriched light harvesting
      chlorosomes of the green photosynthetic bacterium Chlorobium tepidum. A complete
      assignment of 29 different observable resonances of the 61 protons of the
      aggregated BChl c in the intact chlorosomes is obtained. Aggregation shifts
      relative to monomeric BChl c in solution are detected for protons attached to
      rings I, II, and III/V and to their side chains. The 2(1)-H(3), 3(2)-H(3), and
      3(1)-H resonances are shifted upfield by -2.2, -1, and -3.3 ppm, respectively,
      relative to monomeric BChl c in solution. Although the resonances are
      inhomogeneously broadened and reveal considerable global structural
      heterogeneity, the 5-CH and the 7-Me responses are doubled, which provides
      evidence for the existence of at least two relatively well-defined structurally
      different arrangements. Ab initio quantum chemical modeling studies were
      performed to refine a model for the self-assembled BChl c with two different
      types of BChl stacks. The BChl in the stacks can adopt either anti- or syn
      configuration of the coordinative bond, where anti and syn designate the relative
      orientation of the Mg-OH bond relative to the direction of the 17-17(1) bond. The
      analogy between aggregation shifts for BChl c in the chlorosome and for self
      assembled chlorophyll a/H(2)O is explored, and a bilayer model for the tubular
      supra-structure of sheets of BChl c is proposed, from a homology modeling
      approach.

PMID- 11327818
TI  - Dimerization and folding of LC8, a highly conserved light chain of cytoplasmic
      dynein.
AB  - Cytoplasmic dynein is a multisubunit ATPase that transforms chemical energy into
      motion along microtubules. LC8, a 10 kDa light chain subunit of the dynein
      complex, is highly conserved with 94% sequence identity between Drosophila and
      human. The precise function of this protein is unknown, but its ubiquitous
      expression and conservation suggest a critical role in the function of the dynein
      motor complex. We have overexpressed LC8 from Drosophila melanogaster and
      characterized its dimerization and folding using analytical ultracentrifugation,
      size-exclusion chromatography, circular dichroism, and fluorescence spectroscopy.
      Sedimentation equilibrium measurements of LC8 at pH 7 reveal a reversible monomer
      dimer equilibrium with a dissociation constant of 12 microM at 4 degrees C. At
      lower pH, LC8 dissociates to a monomer, with a transition midpoint at pH 4.8. Far
      UV CD and fluorescence spectra demonstrate that pH-dissociated LC8 retains native
      secondary and tertiary structures, while the diminished near-UV CD signal shows
      loss of quaternary structure. The observation that dimeric LC8 dissociates at low
      pH can be explained by titration of a histidine pair in the dimer interface.
      Equilibrium denaturation experiments with a protein concentration range spanning
      almost 2 orders of magnitude indicate that unfolding of LC8 dimer is a two-stage
      process, in which global unfolding is preceded by dissociation to a folded
      monomer. The nativelike tertiary structure of the monomer suggests a role for the
      monomer-dimer equilibrium of LC8 in dynein function.

PMID- 11327819
TI  - C-terminal truncation and histidine-tagging of cytochrome c oxidase subunit II
      reveals the native processing site, shows involvement of the C-terminus in
      cytochrome c binding, and improves the assay for proton pumping.
AB  - To enable metal affinity purification of cytochrome c oxidase reconstituted into
      phospholipid vesicles, a histidine-tag was engineered onto the C-terminal end of
      the Rhodobacter sphaeroides cytochrome c oxidase subunit II. Characterization of
      the natively processed wildtype oxidase and artificially processed forms
      (truncated with and without a his-tag) reveals Km values for cytochrome c that
      are 6-14-fold higher for the truncated and his-tagged forms than for the
      wildtype. This lowered ability to bind cytochrome c indicates a previously
      undetected role for the C-terminus in cytochrome c binding and is mimicked by
      reduced affinity for an FPLC anion exchange column. The elution profiles and
      kinetics indicate that the removal of 16 amino acids from the C-terminus,
      predicted from the known processing site of the Paracoccus denitrificans oxidase,
      does not produce the same enzyme as the native processing reaction. MALDI-TOF MS
      data show the true C-terminus of subunit II is at serine 290, three amino acids
      longer than expected. When the his-tagged form is reconstituted into lipid
      vesicles and further purified by metal affinity chromatography, significant
      improvement is observed in proton pumping analysis by the stopped-flow method.
      The improved kinetic results are attributed to a homogeneous, correctly oriented
      vesicle population with higher activity and less buffering from extraneous
      lipids.

PMID- 11327820
TI  - Crystal structures and iron release properties of mutants (K206A and K296A) that
      abolish the dilysine interaction in the N-lobe of human transferrin.
AB  - Human transferrin (Tf) is responsible for the binding and transport of iron in
      the bloodstream of vertebrates. Delivery of this bound iron to cells occurs by a
      process of receptor-mediated endocytosis during which Tf releases its iron at the
      reduced endosomal pH of approximately 5.6. Iron release from Tf involves a large
      conformational change in which the two domains that enclose the binding site in
      each lobe move apart. We have examined the role of two lysines, Lys206 and
      Lys296, that form a hydrogen-bonded pair close to the N-lobe binding site of
      human Tf and have been proposed to form a pH-sensitive trigger for iron release.
      We report high-resolution crystal structures for the K206A and K296A mutants of
      the N-lobe half-molecule of Tf, hTf/2N, and quantitative iron release data on
      these mutants and the double mutant K206A/K296A. The refined crystal structures
      (for K206A, R = 19.6% and R(free) = 23.7%; for K296A, R= 21.2% and R(free) =
      29.5%) reveal a highly conserved hydrogen bonding network in the dilysine pair
      region that appears to be maintained even when individual hydrogen bonding groups
      change. The iron release data show that the mutants retain iron to a pH 1 unit
      lower than the pH limit of wild type hTf/2N, and release iron much more slowly as
      a result of the loss of the dilysine interaction. Added chloride ions are shown
      to accelerate iron release close to the pH at which iron is naturally lost and
      the closed structure becomes destabilized, and to retard it at higher pH.

PMID- 11327821
TI  - Analysis of etoposide binding to subdomains of human DNA topoisomerase II alpha
      in the absence of DNA.
AB  - Epipodophyllotoxins are effective anti-tumor drugs that inhibit eukaryotic DNA
      topoisomerase II by trapping the enzyme in a covalent complex with DNA. We show
      that both the recombinant N-terminal ATPase domain and the B'A' core domain of
      human topoisomerase IIalpha (htopoIIalpha) bind radiolabeled etoposide
      specifically, even in the absence of DNA. The addition of ATP impairs etoposide
      binding to the holoenzyme and the N-terminal domain, but not to the core domain.
      To see if this interference resembles that between novobiocin and ATP in the
      bacterial GyrB subunit, we modeled the structure of the N-terminal domain of
      htopoIIalpha and performed molecular docking analysis with etoposide. Mutagenesis
      of critical amino acids, predicted to stabilize the drug within the N-terminal
      domain, reveals a less efficient binding of etoposide to the mutated proteins as
      monitored by direct drug binding assays, although the binding of ATP is not
      affected.

PMID- 11327822
TI  - The acetylation state of human fetal hemoglobin modulates the strength of its
      subunit interactions: long-range effects and implications for histone
      interactions in the nucleosome.
AB  - The source of the 70-fold increased tetramer strength of liganded fetal
      hemoglobin relative to that of adult hemoglobin between pH 6.0 and 7.5 reported
      earlier [Dumoulin et al. (1997) J. Biol. Chem. 272, 31326] has been identified as
      the N-terminal Gly residue of the gamma-chain, which is replaced by Val in adult
      hemoglobin. This was revealed by extending the study of the pH dependence of the
      tetramer-dimer equilibrium of these hemoglobins into the alkaline range as far as
      pH 9. From pH 7.5 to 9.0, the 70-fold difference in the association equilibrium
      constant between hemoglobins F and A lessened progressively. This behavior was
      attributed to the difference in the pK(a) 8.1 of Gly-1(gamma) compared to the
      pK(a) 7.1 value of Val-1(beta) of hemoglobins F and A, respectively. Evidence for
      this conclusion was obtained by demonstrating that natural hemoglobin F(1), which
      is specifically acetylated at Gly-1(gamma) and hence unable to be protonated,
      behaves like HbA and not HbF in its tetramer-dimer association properties over
      the pH range studied. An increased degree of protonation of the gamma-chain N
      terminus of hemoglobin F from pH 9.0 to 8.0 is therefore suggested as responsible
      for its increased tetramer strength representing an example of transmission of a
      signal from its positively charged N-terminal tail to the distant subunit
      allosteric interface where the equilibrium constant is measured. An analogy is
      made between the effects of acetylation of the fetal hemoglobin tetramer on the
      strength of its subunit interactions and acetylation of some internal Lys
      residues within the N-terminal segments of the histone octamer around which DNA
      is wrapped in the nucleosome.

PMID- 11327823
TI  - Familial mutations and zinc stoichiometry determine the rate-limiting step of
      nitrocefin hydrolysis by metallo-beta-lactamase from Bacteroides fragilis.
AB  - The diverse members of the metallo-beta-lactamase family are a growing clinical
      threat evolving under considerable selective pressure. The enzyme from Bacillus
      cereus differs from the Bacteroides fragilis enzyme in sequence, zinc
      stoichiometry, and mechanism. To chart the evolution of the more reactive B.
      fragilis enzyme, we have made changes in an active site cysteine residue as well
      as in zinc content to mimic that which occurs in the B. cereus enzyme.
      Specifically, by introducing a C104R mutation into the B. fragilis enzyme,
      binding of two zinc ions is maintained, but the k(cat) value for nitrocefin
      hydrolysis is decreased from 226 to 14 s(-)(1). Removal of 1 equiv of zinc from
      this mutant further decreases k(cat) to 4.4 s(-)(1). In both cases, the observed
      k(cat) closely approximates that found in the di- and monozinc forms of the B.
      cereus enzyme (12 and 6 s(-)(1), respectively). Pre-steady-state stopped-flow
      studies using nitrocefin as a substrate indicate that these enzyme forms share a
      similar mechanism featuring an anionic intermediate but that the rate-limiting
      step changes from protonation of that species to the C-N bond cleavage leading to
      the intermediate. Overall, features that contribute 3.7 kcal/mol toward the
      acceleration of the C-N bond cleavage step have been uncovered although some of
      the total acceleration is masked in the steady-state by a change in rate-limiting
      step. These experiments illustrate one step in the evolution of a catalytic
      mechanism and, in a larger perspective, one step in the evolution of antibiotic
      resistance mechanisms.

PMID- 11327824
TI  - A quantitative model for allosteric control of purine reduction by murine
      ribonucleotide reductase.
AB  - The reduction of purine nucleoside diphosphates by murine ribonucleotide
      reductase requires catalytic (R1) and free radical-containing (R2) enzyme
      subunits and deoxynucleoside triphosphate allosteric effectors. A quantitative 16
      species model is presented, in which all pertinent equilibrium constants are
      evaluated, that accounts for the effects of the purine substrates ADP and GDP,
      the deoxynucleoside triphosphate allosteric effectors dGTP and dTTP, and the
      dimeric murine R2 subunit on both the quaternary structure of murine R1 subunit
      and the dependence of holoenzyme (R1(2)R2(2)) activity on substrate and effector
      concentrations. R1, monomeric in the absence of ligands, dimerizes in the
      presence of substrate, effectors, or R2(2) because each of these ligands binds
      R1(2) with higher affinity than R1 monomer. This leads to apparent positive
      heterotropic cooperativity between substrate and allosteric effector binding that
      is not observed when binding to the dimeric protein itself is evaluated.
      Allosteric activation results from an increase in k(cat) for substrate reduction
      upon binding of the correct effector, rather than from heterotropic cooperativity
      between effector and substrate. Neither the allosteric site nor the active site
      displays nucleotide base specificity: dissociation constants for dGTP and dTTP
      are nearly equivalent and K(m) and k(cat) values for both ADP and GDP are
      similar. R2(2) binding to R1(2) shows negative heterotropic cooperativity vis-a
      vis effectors but positive heterotropic cooperativity vis-a-vis substrates.
      Binding of allosteric effectors to the holoenzyme shows homotropic cooperativity,
      suggestive of a conformational change induced by activator binding. This is
      consistent with kinetic results indicating full dimer activation upon binding a
      single equivalent of effector per R1(2)R2(2).

PMID- 11327825
TI  - Antibody 17b binding at the coreceptor site weakens the kinetics of the
      interaction of envelope glycoprotein gp120 with CD4.
AB  - HIV-1 utilizes CD4 and the chemokine coreceptor for viral entry. The coreceptor
      CCR5 binding site on gp120 partially overlaps with the binding epitope of 17b, a
      neutralizing antibody of HIV-1. We designed a multicomponent biosensor assay to
      investigate the kinetic mechanism of interaction between gp120 and its receptors
      and the cooperative effect of the CCR5 binding site on the CD4 binding site,
      using 17b as a surrogate of CCR5. The Env gp120 proteins from four viral strains
      (JRFL, YU2, 89.6, and HXB2) and their corresponding C1-, V1/V2-, C5-deleted
      mutants (DeltaJRFL, DeltaYU2, Delta89.6, and DeltaHXB2) were tested in this
      study. We found that, across the primary and lab-adapted virus strains, 17b
      reduced the affinity of all four full-length Env gp120s for sCD4 by decreasing
      the on-rate and increasing the off-rate. This effect of 17b on full-length gp120
      binding to sCD4 contrasts with the enhancing effect of sCD4 on gp120-17b
      interaction. For the corresponding loop-deleted mutants of Env gp120, the off
      rates of the gp120-sCD4 interaction were greatly reduced in the presence of 17b,
      resulting in higher affinities (except for that of DeltaHXB2). The results
      suggest that, when 17b is prebound to full-length gp120, the V1/V2 loops may be
      relocated to a position that partially blocks the CD4-binding site, leading to
      weakening of the CD4 interaction. Given the fact that the 17b binding epitope
      partially overlaps with the binding site of CCR5, the kinetic results suggest
      that coreceptor CCR5 binding could have a similar "release" effect on the gp120
      CD4 interaction by increasing the off-rate of the latter. The results also
      suggest that the neutralizing effect of 17b may arise not only from partially
      blocking the CCR5 binding site but also from reducing the CD4 binding affinity of
      gp120. This negative cooperative effect of 17b may provide insight into
      approaches to designing antagonists for viral entry.

PMID- 11327826
TI  - Human recombinant pro-dipeptidyl peptidase I (cathepsin C) can be activated by
      cathepsins L and S but not by autocatalytic processing.
AB  - Human dipeptidyl peptidase I was expressed in the insect cell/baculovirus system
      and purified in its active (rhDPPI) and precursor (pro-rhDPPI) forms. RhDPPI was
      very similar to the purified enzyme (hDPPI) with respect to glycosylation,
      enzymatic processing, oligomeric structure, CD spectra, and catalytic activity.
      The precursor, which was a dimer, could be activated approximately 2000-fold with
      papain. Cathepsin L efficiently activated pro-rhDPPI in vitro at pH 4.5 (k(app)
      approximately 2 x 10(3) min(-)(1) M(-)(1)), and two cleavage pathways were
      characterized. The initial cleavage was within the pro region between the
      residual pro part and the activation peptide. Subsequently, the activation
      peptide was cleaved from the catalytic region, and the latter was cleaved into
      the heavy and light chains. Alternatively, the pro region was first separated
      from the catalytic region. Cathepsin S was a less efficient activating enzyme.
      Cathepsin B and rhDPPI did not activate pro-rhDPPI, and the proenzyme was
      incapable of autoactivation. Incubation of both pro-rhDPPI and rhDPPI with
      cathepsin D resulted in degradation. Cystatin C and stefins A and B inhibited
      rhDPPI with K(i) values in the nanomolar range (K(i) = 0.5-1.1 nM). The results
      suggest that cathepsin L could be an important activator of DPPI in vivo and that
      cathepsin D and possibly the cystatins may contribute to DPPI downregulation.

PMID- 11327827
TI  - Activation of prostate-specific antigen precursor (pro-PSA) by prostin, a novel
      human prostatic serine protease identified by degenerate PCR.
AB  - A novel serine protease was found in human prostate by degenerate oligonucleotide
      PCR amplification and cloned. The zymogen form of this enzyme, named prostinogen,
      is composed of 240 amino acid residues with an amino-terminal propiece of 5
      residues and a 235-residue mature enzyme. The transcript has a signal peptide of
      15 amino acid residues. The mature enzyme has 41% sequence identity with prostate
      specific antigen (PSA). Prostinogen was expressed in Escherichia coli and
      refolded from inclusion bodies. The zymogen, with a molecular mass of 28 kDa, was
      readily activated by agarose-immobilized trypsin to generate prostin, a serine
      protease, which cleaves the chromogenic substrate (N-benzoyl-L-Ile-L-Glu-L-Gly-L
      Arg-p-nitroaniline hydrochloride) (S-2222). Recombinant prostin readily activates
      the precursor of PSA (pro-PSA) by cleavage of the amino terminal Arg(7)-Ile(8)
      peptide bond. These results indicate that prostin may be a physiological
      activator of pro-PSA following its own proteolytic activation, as part of a
      cascade system involving a series of serine protease precursor proteins in the
      prostate.

PMID- 11327828
TI  - Inhibition of NF-kappa B by S-nitrosylation.
AB  - It is not clear if redox regulation of transcription is the consequence of direct
      redox-related modifications of transcription factors, or if it occurs at some
      other redox-sensitive step. One obstacle has been the inability to demonstrate
      redox-related modifications of transcription factors in vivo. The redox-sensitive
      transcriptional activator NF-kappaB (p50-p65) is a case in point. Its activity in
      vitro can be inhibited by S-nitrosylation of a critical thiol in the DNA
      interacting p50 subunit, but modulation of NF-kappaB activity by nitric oxide
      synthase (NOS) has been attributed to other mechanisms. Herein we show that
      cellular NF-kappaB activity is in fact regulated by S-nitrosylation. We observed
      that both S-nitrosocysteine and cytokine-activated NOS2 inhibited NF-kappaB in
      human respiratory cells or murine macrophages. This inhibition was reversed by
      addition of the denitrosylating agent dithiothreitol to cellular extracts,
      whereas NO bioactivity did not affect the TNFalpha-induced degradation of
      IkappaBalpha or the nuclear translocation of p65. Recapitulation of these
      conditions in vitro resulted in S-nitrosylation of recombinant p50, thereby
      inhibiting its binding to DNA, and this effect was reversed by dithiothreitol.
      Further, an increase in S-nitrosylated p50 was detected in cells, and the level
      was modulated by TNFalpha. Taken together, these data suggest that S
      nitrosylation of p50 is a physiological mechanism of NF-kappaB regulation.

PMID- 11327829
TI  - Substrate specificity of the integral membrane protease OmpT determined by
      spatially addressed peptide libraries.
AB  - Escherichia coli outer membrane protease T (OmpT) is an endopeptidase that
      specifically cleaves between two consecutive basic residues. In this study we
      have investigated the substrate specificity of OmpT using spatially addressed
      SPOT peptide libraries. The peptide acetyl-Dap(dnp)-Ala-Arg/Arg-Ala-Lys(Abz)-Gly
      was synthesized directly onto cellulose membrane. The peptide contained the
      aminobenzoyl (Abz) fluorophore, which was internally quenched by the
      dinitrophenyl (dnp) moiety. Treatment of the SPOT membrane with the small, water
      soluble protease trypsin resulted in highly fluorescent peptide SPOTs. However,
      no peptide cleavage was observed after incubation with detergent-solubilized
      OmpT, a macromolecular complex with an estimated molecular mass of 180 kDa. This
      problem could be solved by the introduction of a long, polar polyoxyethylene
      glycol linker between the membrane support and the peptide. Peptide libraries for
      the P(2), P(1), P(1)', and P(2)' positions in the substrate were screened with
      OmpT, and peptides of positive SPOTs were resynthesized and subjected to kinetic
      measurements in solution. The best substrate Abz-Ala-Lys-Lys-Ala-Dap(dnp)-Gly had
      a turnover number k(cat) of 40 s(-)(1), which is 12-fold higher than the starting
      substrate. Peptides containing an acidic residue at P(2) or P(2)' were not
      substrates for OmpT, suggesting that long-range electrostatic interactions are
      important for the formation of the enzyme-substrate complex. OmpT was highly
      selective toward L-amino acids at P(1) but was less so at P(1)' where a peptide
      with D-Arg at P(1)' was a competitive inhibitor (K(i) of 19 microM). An affinity
      chromatography resin based on these findings was developed, which allowed for the
      one-step purification of OmpT from a bacterial lysate. The implications of the
      determined consensus substrate sequence (Arg/Lys)/(Arg/Lys)-Ala for the proposed
      biological function of OmpT in defense against antimicrobial peptides are
      discussed.

PMID- 11327830
TI  - Tyrosine kinase-mediated serine phosphorylation of adenylyl cyclase.
AB  - Receptor tyrosine kinase (RTK) activation is associated with modulation of
      heptahelical receptor-stimulated adenylyl cyclase responses. The mechanisms
      underlying the RTK-mediated enhancement of adenylyl cyclase function remain
      unclear. In the present studies, we show that the tyrosine kinase-dependent
      enhancement of adenylyl cyclase isoform VI function parallels an enhancement in
      serine phosphorylation of the enzyme. This effect was mediated by both RTK
      activation, with IGF-1, and by tyrosine phosphatase inhibition, with sodium
      orthovanadate. This enhancement of adenylyl cyclase function was not attenuated
      by inhibitors of ERK, PKC, PKA, or PI3 kinase activity but was blunted by
      inhibition of endogenous p74(raf-1)() activity. To characterize the molecular
      site of this effect we identified multiple candidate serine residues in and
      adjacent to the adenylyl cyclase VI C1b catalytic region and performed serine-to
      alanine site-directed mutagenesis using adenylyl cyclase VI as a template.
      Mutation of serine residues 603 and 608 or serine residues 744, 746, 750, and 754
      attenuated both the tyrosine kinase-mediated enhancement of enzyme
      phosphorylation as well as the sensitization of function. Together, these data
      define a novel tyrosine kinase-mediated mechanism leading to serine
      phosphorylation of adenylyl cyclase isoform VI and the sensitization of adenylyl
      cyclase responsiveness.

PMID- 11327831
TI  - Cysteine substitutions in apolipoprotein A-I primary structure modulate
      paraoxonase activity.
AB  - Paraoxonase (PON) is transported primarily on apolipoprotein A-I (apoA-I) 
      containing high-density lipoprotein (HDL) and is thought to protect against early
      atherogenic events including low-density lipoprotein (LDL) oxidation and monocyte
      migration. It has been proposed that apoA-I may be necessary for PON's
      association with plasma HDL. On the basis of this, we examined the effect of apoA
      I on PON's enzymatic activity and its ability to associate with HDL.
      Additionally, we examined whether changes in apoA-I primary structure (cysteine
      substitution mutations) could modulate these effects. Chinese hamster ovary cells
      stably transfected with human PON1A cDNA were incubated in the presence and
      absence of recombinant wild-type apoA-I (apoA-I(WT)) and specific Cys
      substitution mutations. Extracellular accumulation of PON activity in the
      presence of apoA-I(WT) was 0.095 +/- 0.013 unit/mg of cell protein (n = 7)
      compared to 0.034 +/- 0.010 unit/mg of cell protein in the absence of apoA-I (n =
      7), a 2.79-fold increase in activity when apoA-I was incubated with the cells.
      Lipid-free apoA-I did not increase PON activity, while preformed nascent HDL
      increased PON activity only 30%, suggesting that maximal PON activity is lipid
      dependent and requires coassembly of PON and apoA-I on nascent HDL. The cysteine
      mutations R10C, R27C, and R61C significantly increased (p < 0.01) PON activity
      32.6% +/- 14.7%, 31.6% +/- 18.9%, and 27.4% +/- 20%, respectively, over that of
      wild type (WT). No changes in PON activity were observed with apoA-I cysteine
      substitution mutations in the C-terminal portion of the protein. The data suggest
      that, for optimal PON activity, coassembly of the enzyme onto nascent HDL is
      required and that the N-terminal region of apoA-I may be important in the
      assembly process.

PMID- 11327832
TI  - Is the oxidation of high-density lipoprotein lipids different than the oxidation
      of low-density lipoprotein lipids?
AB  - This article gives detailed insight into the kinetics of high-density lipoprotein
      (HDL) oxidation catalyzed by azobis(2-amidinopropane).dihydrochloride (ABAP) or
      by copper. ABAP initialized oxidation of human HDL 3-4 times faster than non
      human primate HDL with a similar composition. The oxidizability of non-human
      primate HDL was 1000 times lower than the oxidizability calculated from rate
      constants derived from liposome oxidation, suggesting that there is a slow step
      in HDL oxidation not present in liposomes. Saturable binding of copper to HDL was
      a significant feature of copper-catalyzed oxidation. Binding constants (K(m)) for
      non-human primate HDL were 2-3-fold lower than those for human HDL. Copper
      catalyzed oxidation of non-human primate HDL was slower than that of human HDL,
      but human HDL(2) and HDL(3) oxidized at about the same rate. Overall, the
      kinetics describing the oxidation of HDL were mechanistically similar to those
      reported for LDL, suggesting that HDL lipids were as easily oxidized as LDL
      lipids and that HDL will be easily oxidized in vivo when exposed to agents that
      oxidize LDL.

PMID- 11327833
TI  - Involvement of glycine 141 in substrate activation by enoyl-CoA hydratase.
AB  - Raman spectroscopy has been used to investigate the structure of a substrate
      analogue, hexadienoyl-CoA (HD-CoA), bound to wild-type enoyl-CoA hydratase and
      G141P, a mutant in which a hydrogen bond to the substrate carbonyl has been
      removed. Raman spectra of isotopically labeled HD-CoAs, together with normal mode
      calculations, confirm the selective ground-state polarization of the enone
      fragment previously suggested to occur on binding to the wild-type enzyme [Tonge,
      P. J., Anderson, V. E., Fausto, R., Kim, M., Pusztai-Carey, M., and Carey, P. R.
      (1995) Biospectroscopy 1, 387-394]. In addition, Raman spectra of HD-CoA bound to
      the G141P mutant enzyme demonstrate that the hydrogen bond between the G141 amide
      NH group and the substrate carbonyl is critical for polarization and activity.
      Replacement of G141 with proline results in an approximately 10(6)-fold decrease
      in k(cat) and eliminates the ability of the enzyme to polarize the substrate
      analogue. As G141 is part of a consensus sequence in the enoyl-CoA hydratase
      superfamily, the results presented here provide direct evidence for the
      importance of the oxyanion hole in the reactions catalyzed by other family
      members.

PMID- 11327834
TI  - Escherichia coli dimethylallyl diphosphate:tRNA dimethylallyltransferase: site
      directed mutagenesis of highly conserved residues.
AB  - Dimethylallyl diphosphate:tRNA dimethylallyltransferase (DMAPP-tRNA transferase)
      catalyzes alkylation of the exocyclic amine of adenosine at position 37 in some
      tRNAs by the hydrocarbon moiety of dimethylallyl diphosphate (DMAPP). A multiple
      sequence alignment of 28 gene sequences encoding DMAPP-tRNA transferases from
      various organisms revealed considerable homology, including 11 charged, 12 polar,
      and four aromatic amino acids that are highly conserved or conservatively
      substituted. Site-directed mutants were constructed for all of these amino acids,
      and a tripeptide Glu-Glu-Phe alpha-tubulin epitope was appended to the C-terminus
      of the protein to facilitate separation by immunoaffinity chromatography of
      overproduced mutant enzymes from coexpressed chromosomally encoded wild-type
      DMAPP-tRNA transferase. Steady-state kinetic constants were measured for wild
      type DMAPP-tRNA transferase and the site-directed mutants using DMAPP and a 17
      base RNA oligoribonucleotide corresponding to the stem-loop region of tRNA(Phe)
      as substrates. Substantial changes in k(cat), K(m)(DMAPP), and/or K(m)(RNA) were
      seen for several of the mutants, suggesting possible roles for these residues in
      substrate binding and catalysis.

PMID- 11327835
TI  - Structural and kinetic analysis of the chemical rescue of the proton transfer
      function of carbonic anhydrase II.
AB  - Histidine 64 in human carbonic anhydrase II (HCA II) functions in the catalytic
      pathway of CO(2) hydration as a shuttle to transfer protons between the zinc
      bound water and bulk water. Catalysis of the exchange of (18)O between CO(2) and
      water, measured by mass spectrometry, is dependent on this proton transfer and
      was decreased more than 10-fold for H64A HCA II compared with wild-type HCA II.
      The loss of catalytic activity of H64A HCA II could be rescued by 4
      methylimidazole (4-MI), an exogenous proton donor, in a saturable process with a
      maximum activity of 40% of wild-type HCA II. The crystal structure of the rescued
      complex at 1.6 A resolution shows 4-MI bound in the active-site cavity of H64A
      HCA II, through pi stacking interactions with Trp 5 and H-bonding interactions
      with water molecules. In this location, 4-MI is about 12 A from the zinc and
      approximates the observed "out" position of His 64 in the structure of the wild
      type enzyme. 4-MI appears to compensate for the absence of His 64 and rescues the
      catalytic activity of the H64A HCA II mutant. This result strongly suggests that
      the out conformation of His 64 is effective in the transfer of protons between
      the zinc-bound solvent molecule and solution.

PMID- 11327836
TI  - Differential transfers of reduced flavin cofactor and product by bacterial flavin
      reductase to luciferase.
AB  - It is believed that the reduced FMN substrate required by luciferase from
      luminous bacteria is provided in vivo by NAD(P)H-FMN oxidoreductases (flavin
      reductases). Our earlier kinetic study indicates a direct flavin cofactor
      transfer from Vibrio harveyi NADPH-preferring flavin reductase P (FRP(H)) to the
      luciferase (L(H)) from the same bacterium in the in vitro coupled luminescence
      reaction. Kinetic studies were carried out in this work to characterize coupled
      luminescence reactions using FRP(H) and the Vibrio fischeri NAD(P)H-utilizing
      flavin reductase G (FRG(F)) in combination with L(H) or luciferase from V.
      fischeri (L(F)). Comparisons of K(m) values of reductases for flavin and pyridine
      nucleotide substrates in single-enzyme and luciferase-coupled assays indicate a
      direct transfer of reduced flavin, in contrast to free diffusion, from reductase
      to luciferase by all enzyme couples tested. Kinetic mechanisms were determined
      for the FRG(F)-L(F) and FRP(H)-L(F) coupled reactions. For these two and the
      FRG(F)-L(H) coupled reactions, patterns of FMN inhibition and effects of
      replacement of the FMN cofactor of FRP(H) and FRG(F) by 2-thioFMN were also
      characterized. Similar to the FRP(H)-L(H) couple, direct cofactor transfer was
      detected for FRG(F)-L(F) and FRP(H)-L(F). In contrast, despite the structural
      similarities between FRG(F) and FRP(H) and between L(F) and L(H), direct flavin
      product transfer was observed for the FRG(F)-L(H) couple. The mechanism of
      reduced flavin transfer appears to be delicately controlled by both flavin
      reductase and luciferase in the couple rather than unilaterally by either enzyme
      species.

PMID- 11327837
TI  - Consequences of a modified putative substrate-activation site on catalysis by
      yeast pyruvate decarboxylase.
AB  - Earlier, it had been proposed in the laboratories at Halle that a cysteine
      residue is responsible for the hysteretic substrate activation behavior of yeast
      pyruvate decarboxylase. More recently, this idea has received support in a series
      of studies from Rutgers with the identification of residue C221 as the site where
      substrate is bound to transmit the information to H92, to E91, to W412, and
      finally to the active center thiamin diphosphate. According to steady-state
      kinetic assays, the C221A/C222A variant is no longer subject to substrate
      activation yet is still a well-functioning enzyme. Several further experiments
      are reported on this variant: (1) The variant exhibits lag phases in the product
      formation progress curves, which can be attributed to a unimolecular step in the
      pre-steady-state stage of catalysis. (2) The rate of exchange with solvent
      deuterium of the thiamin diphosphate C2H atom is slowed by a factor of 2 compared
      to the wild-type enzyme, suggesting that the reduced activity that results from
      the substitutions some 20 A from the active center is also seen in the first key
      step of the reaction. (3) The solvent (deuterium oxide) kinetic isotope effect
      was found to be inverse on V(max)/K(m) (0.62), and small but normal on V(max)
      (1.26), virtually ruling out residue C221 as being responsible for the inverse
      effects reported for the wild-type enzyme at low substrate concentrations. The
      solvent kinetic isotope effects are compared to those on two related enzymes not
      subject to substrate activation, Zymomonas mobilis pyruvate decarboxylase and
      benzoylformate decarboxylase.

PMID- 11327839
TI  - Van't Hoff and calorimetric enthalpies from isothermal titration calorimetry: are
      there significant discrepancies?
AB  - The enthalpy of a reaction is most often determined through one of two means; it
      can be determined directly using calorimetry or indirectly by measuring the
      temperature dependence of the equilibrium constant (i.e., the van't Hoff method).
      Recently, discrepancies have been noted between the enthalpy measured by
      calorimetry, and the enthalpy determined by the van't Hoff method,. This has been
      suggested to indicate that the binding reaction is more complex than the simple
      one-to-one binding model used to describe the data. To better understand possible
      discrepancies between and, we have undertaken both experimental studies using
      isothermal titration calorimetry to measure the binding energetics of Ba(2+)
      binding 18-crown-6 ether and 2'-CMP binding RNase A, along with a simulation of a
      system involving a molecule in conformational equilibrium coupled with binding.
      We find that when experimental setup and analysis are correctly performed, no
      statistically significant discrepancies between and exist even for the linked
      system.

PMID- 11327838
TI  - Stability, folding, dimerization, and assembly properties of the yeast prion
      Ure2p.
AB  - The [URE3] factor of Saccharomyces cerevisiae propagates by a prion-like
      mechanism and corresponds to the loss of the function of the cellular protein
      Ure2. The molecular basis of the propagation of this phenotype is unknown. We
      recently expressed Ure2p in Escherichia coli and demonstrated that the N-terminal
      region of the protein is flexible and unstructured, while its C-terminal region
      is compactly folded. Ure2p oligomerizes in solution to form mainly dimers that
      assemble into fibrils [Thual et al. (1999) J. Biol. Chem. 274, 13666-13674]. To
      determine the role played by each domain of Ure2p in the overall properties of
      the protein, specifically, its stability, conformation, and capacity to assemble
      into fibrils, we have further analyzed the properties of Ure2p N- and C-terminal
      regions. We show here that Ure2p dimerizes through its C-terminal region. We also
      show that the N-terminal region is essential for directing the assembly of the
      protein into a particular pathway that yields amyloid fibrils. A full-length
      Ure2p variant that possesses an additional tryptophan residue in its N-terminal
      moiety was generated to follow conformational changes affecting this domain.
      Comparison of the overall conformation, folding, and unfolding properties, and
      the behavior upon proteolytic treatments of full-length Ure2p, Ure2pW37 variant,
      and Ure2p C-terminal fragment reveals that Ure2p N-terminal domain confers no
      additional stability to the protein. This study reveals the existence of a stable
      unfolding intermediate of Ure2p under conditions where the protein assembles into
      amyloid fibrils. Our results contradict the intramolecular interaction between
      the N- and C-terminal moieties of Ure2p and the single unfolding transitions
      reported in a number of previous studies.

PMID- 11327840
TI  - Stimulation of RecA-mediated D-loop formation by oligonucleotide-directed triple
      helix formation: guided homologous recombination (GOREC).
AB  - Oligonucleotide-directed triple helix formation provides an elegant rational
      basis for gene-specific DNA targeting and has been widely used to interfere with
      gene expression ("antigene" strategies) and as a molecular tool for biological
      studies. Various strategies have been developed to introduce sequence
      modifications in genomes. However, the low efficiency of the overall process in
      eucaryotic cells impairs efficient recovery of recombinant genomes. Since one
      limiting step in homologous recombination is the targeting to the homologous
      sequence, we have tested the contribution of an oligonucleotide-directed triple
      helix formation on the RecA-dependent association of an oligonucleotide and its
      homologous target on duplex DNA (D-loop formation). For this study, the
      recombinant ssDNA fragment was noncovalently associated to a triple helix-forming
      oligonucleotide. The physicochemical and biochemical characteristics of the
      triple helix and D-loop structures formed by the complex molecules in the
      presence or in the absence of RecA protein were determined. We have demonstrated
      that the triple helix-forming oligonucleotide increases the efficiency of D-loop
      formation and the RecA protein speeds up also the triple helix formation. The so
      called "GOREC" (for guided homologous recombination) approach can be developed as
      a novel tool to improve the efficiency of directed mutagenesis and gene
      alteration in living organisms.

PMID- 11327841
TI  - Finger-positional change in three zinc finger protein Sp1: influence of terminal
      finger in DNA recognition.
AB  - The connection of functional modules is effective for the design of DNA binding
      molecules with the desired sequence specificity. C(2)H(2)-type zinc finger
      proteins have a tandemly repeated array structure consisting of independent
      finger modules and are expected to recognize any DNA sequences by permutation,
      multi-connection, and the substitution of various sets of zinc fingers. To
      investigate the effects of the replacement of the terminal finger on the DNA
      recognition by other fingers, we have constructed the three zinc finger peptides
      with finger substitution at the N- or C-terminus, Sp1(zf223), Sp1(zf323), and
      Sp1(zf321). From the results of gel mobility shift assays, each mutant peptide
      binds preferentially to the target sequence that is predicted if the fingers act
      in a modular fashion. The methylation interference analyses demonstrate that in
      the cases of the N-terminal finger substitution mutants, Sp1(zf223) and
      Sp1(zf323), the N-terminal finger recognizes bases to different extents from that
      of the wild-type peptide, Sp1(zf123). Of special interest is the fact that the N
      terminal finger of the C-terminal finger substitution mutant, Sp1(zf321), shows a
      distinct base recognition from those of Sp1(zf123) and Sp1(zf323). DNase I
      footprinting analyses indicate that the C-terminal finger (active finger) induces
      a conformational change in the DNA in the region for the binding of the N
      terminal finger (passive finger). The present results strongly suggest that the
      extent of base recognition of the N-terminal finger is dominated by the binding
      of the C-terminal finger. This information provides an important clue for the
      creation of a zinc finger peptide with the desired specificity, which is
      applicable to the design of novel drugs and biological tools.

PMID- 11327842
TI  - Evidence in Escherichia coli that N3-methyladenine lesions induced by a minor
      groove binding methyl sulfonate ester can be processed by both base and
      nucleotide excision repair.
AB  - It has been previously reported that a neutral DNA equilibrium binding agent
      based on an N-methylpyrrolecarboxamide dipeptide (lex) and modified with an O
      methyl sulfonate ester functionality (MeOSO(2)-lex) selectively affords N3
      methyladenine lesions. To study the interaction of the neutral lex dipeptide with
      calf thymus DNA, we have prepared stable, nonmethylating sulfone analogues of
      MeOSO(2)-lex that are neutral and cationic. Thermodynamic studies show that both
      the neutral and monocationic sulfone compounds bind to DNA with K(b)'s of 10(5)
      in primarily entropy-driven reactions. To determine how the cytotoxic N3
      methyladenine adduct generated from MeOSO(2)-lex is repaired in E. coli, MeOSO(2)
      lex was tested for toxicity in wild-type E. coli and in mutant strains defective
      in base excision repair (tag and/or alkA glycosylases or apn endonuclease),
      nucleotide excision repair (uvrA), and both base and nucleotide excision repair
      (tag/alkA/uvrA). The results clearly demonstrate the cellular toxicity of the N3
      methyladenine lesion, and the protective role of base excision glycosylase
      proteins. A novel finding is that in the absence of functional base excision
      glycosylases, nucleotide excision repair can also protect cells from this
      cytotoxic minor groove lesion. Interaction between base and nucleotide excision
      repair systems is also seen in the protection of cells treated with cis
      diamminedichloroplatinum(II) but not with anti-(+/-)-r-7,t-8-dihydroxy-t-9,10
      epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene.

PMID- 11327843
TI  - Resonance energy transfer between tryptophan 57 in the epsilon subunit and pyrene
      maleimide labeled gamma subunit of the chloroplast ATP synthase.
AB  - The intrinsic fluorescence of the catalytic portion of the chloroplast ATP
      synthase (CF1) is quenched when cysteine 322, the penultimate amino acid of the
      gamma subunit, is specifically labeled with pyrene maleimide (PM). The epsilon
      subunit of CF1 contains the only two residues of tryptophan, which dominate the
      intrinsic fluorescence of unlabeled CF1. CF1 deficient in the epsilon subunit
      (CF1-epsilon) was reconstituted with mutant epsilon subunits in which
      phenylalanine replaced tryptophan at position 15 (epsilonW15F) and position 57
      (epsilonW15/57F). CF1(epsilonW15F) containing a single tryptophan, epsilonW57,
      was labeled with PM at gammaC322. Resonance energy transfer (RET) from epsilonW57
      to PM on gammaC322 occurred with an efficiency of energy transfer of 20%. RET was
      also observed from epsilonW57 to PM attached to the disulfide thiols of the gamma
      subunit (gammaC199,205) with an efficiency of approximately 45%. The R(o) (the
      distance at which the efficiency of energy transfer is 50%) for the epsilonW57
      and PM donor/acceptor pair is 30 A, indicating that both gammaC322 and
      gammaC199,205 must be within 40 A of epsilonW57. These RET measurements show that
      both gammaC322 and gammaC199,205 are located near the base of the alpha/beta
      hexamer. This places the C-terminus of CF1 gamma much closer to epsilon than
      hypothesized based on homology to crystal structures of mitochondrial F1. These
      new RET measurements also allow the alignment of the predicted epsilon subunit
      structure. The orientation is similar to that predicted from cross-linking and
      mutational studies for the epsilon subunit of Escherichia coli F1.

PMID- 11327844
TI  - Equilibrium and kinetic parameters for the binding of inhibitors to the QB pocket
      in bacterial chromatophores: dependence on the state of QA.
AB  - The equilibrium and kinetic parameters for the binding of various inhibitors to
      the Q(B) pocket of the bacterial reaction center were investigated in
      chromatophores from Rhodobacter capsulatus and Rhodobacter sphaeroides. By
      monitoring the near-IR absorption changes specific to Q(A)(-) and Q(B)(-), we
      measured the fraction of inhibited centers in the dark and the kinetics and
      extent of inhibitor displacement after one flash due to the formation of the
      Q(A)Q(B)(-) state. The inhibitor release rate was much faster for triazines and o
      phenanthroline (t(1/2) in the 50 ms to 1 s range) than for stigmatellin (t(1/2)
      approximately 20 s). For inhibitors with a rapid release rate, the fast phase of
      P(+) decay observed in the absence of secondary donor reflects the competition
      between P(+)Q(A)(-) recombination and inhibitor release: it is thus faster than
      the P(+)Q(A)(-) recombination, and its relative extent is smaller than the
      fraction of initially inhibited centers. At appropriate inhibitor concentrations,
      one can have almost total binding in the dark and almost total inhibitor
      displacement after one flash. Under such conditions, a pair of closely spaced
      flashes resets the two-electron gate in a single state (Q(A)Q(B)(-)),
      irrespective of the initial state. The apparent dissociation constant of
      terbutryn was significantly increased (by a factor of 4-7) in the presence of
      Q(A)(-), in agreement with the conclusion of Wraight and co-workers [Stein, R.
      R., et al. (1984) J. Cell. Biochem. 24, 243-259]. We suggest that this effect is
      essentially due to a tighter binding of ubiquinone in the Q(A)(-) state.

PMID- 11327845
TI  - Translocation of the pAntp peptide and its amphipathic analogue AP-2AL.
AB  - The pAntp peptide, corresponding to the third helix of the homeodomain of the
      Antennapedia protein, enters by a receptor-independent process into eukaryotic
      cells. The interaction between the pAntp peptide and the phospholipid matrix of
      the plasma membrane seems to be the first step involved in the translocation
      mechanism. However, the mechanism by which the peptide translocates through the
      cell membrane is still not well established. We have investigated the
      translocation ability of pAntp through a protein-free phospholipid membrane in
      comparison with a more amphipathic analogue. We show by fluorescence
      spectroscopy, circular dichroism, NMR spectroscopy, and molecular modeling that
      pAntp is not sufficiently helically amphipathic to cross a phospholipid membrane
      of a model system. Due to its primary sequence related to its DNA binding ability
      in the Antennapedia homeodomain-DNA complex, the pAntp peptide does not belong to
      the amphipathic alpha-helical peptide family whose members are able to
      translocate by pore formation.

PMID- 11327846
TI  - Lipid and signal peptide-induced conformational changes within the C-domain of
      Escherichia coli SecA protein.
AB  - SecA ATPase is an essential component of the Sec-dependent protein translocation
      machinery. Upon interaction with the plasma membrane containing SecYE,
      preprotein, and ATP, SecA undergoes cycles of membrane insertion and retraction
      resulting in the translocation of segments of the preprotein to the trans side of
      the membrane. To study the structural basis of SecA function, we employed
      fluorescence spectroscopy along with collisional quenchers with a set of SecA
      proteins containing single tryptophan substitutions. Our data show that among the
      seven naturally occurring tryptophan residues of Escherichia coli SecA, only the
      three tryptophan residues contained within the C-domain contributed significantly
      to the fluorescence signal, and they occupied distinct local environments in
      solution: Trp723 and Trp775 were found to be relatively solvent accessible and
      inaccessible, respectively, while Trp701 displayed an intermediate level of
      solvent exposure. Exposure to increased temperature or interaction with model
      membranes or signal peptide elicited a similar conformational response from SecA
      based upon the fluorescence signals of the SecA-W775F and SecA-W723F mutant
      proteins. Specifically, Trp775 became more solvent exposed, while Trp723 became
      less solvent accessible under these conditions, indicating similarities in the
      overall conformational change of the C-domain promoted by temperature or
      translocation ligands. Only Trp701 did not respond in parallel to the different
      conditions, since its solvent accessibility changed only in the presence of
      signal peptide. These results provide the first detailed structural information
      about the C-domain of SecA and its response to translocation ligands, and they
      provide insight into the conformational changes within SecA that drive protein
      translocation.

PMID- 11327847
TI  - N-terminal intramolecularly conserved histidines of three domains in Gonyaulax
      luciferase are responsible for loss of activity in the alkaline region.
AB  - Gonyaulax luciferase is a single-chain ( approximately 137 kDa) polypeptide
      comprising 111 N-terminal amino acids followed by three contiguous homologous
      domains (377 amino acids each). Each domain has luciferase activity, accounting
      for the earlier observation that proteolytic fragments ( approximately 35 kDa) of
      luciferase are active. The activity of the full-length native enzyme is maximal
      at pH 6.3, dropping to near zero at pH 8; the activity of fragments also peaks at
      pH 6.3 but remains high at 8. While the activity loss at higher pH might be
      thought to be associated with the conformation of the full-length protein, we
      show here that this is a property of individual domains. The three
      intramolecularly homologous domains, separately cloned and expressed in
      Escherichia coli as fusion proteins, exhibit pH-activity curves similar to that
      of the full-length enzyme. For each domain the removal of approximately 50 N
      terminal amino acids resulted in an increase in the ratio of luciferase activity
      at pH 8 relative to that at pH 6.3, such that their pH-activity profiles mimicked
      that of the proteolytic fragments reported earlier. Replacement of N-terminal
      histidines by alanine by site-directed mutagenesis identified four that are
      involved in the loss of activity at high pH. This system illustrates an unusual,
      possibly unique mechanism for pH regulation of enzyme activity, which has been
      postulated to be responsible for the control of the characteristic flashes of
      bioluminescence.

PMID- 11327848
TI  - Retardation of proton transfer caused by binding of the transition metal ion to
      the bacterial reaction center is due to pKa shifts of key protonatable residues.
AB  - Transition metal ions bind to the reaction center (RC) protein of the
      photosynthetic bacterium Rhodobacter sphaeroides and slow the light-induced
      electron and proton transfer to the secondary quinone, Q(B). We studied the
      properties of the metal ion-RC complex by measuring the pH dependence of the
      dissociation constant and the stoichiometry of proton release upon ligand
      formation. We investigated the mechanism of inhibition by measuring the
      stoichiometry and kinetics of flash-induced proton binding, the transfer of
      (first and second) electrons to Q(B), and the rate of steady-state turnover of
      the RC in the absence and presence of Cd(2+) and Ni(2+) on a wide pH range. The
      following results were obtained. (1) The complexation of transition metal ions
      Cd(2+) and Ni(2+) with the bacterial RC showed strong pH dependence. This
      observation was explained by different (pH-dependent) states of the metal-ligand
      cluster: the complex formation was strong when the ligand (Asp and His residues)
      was deprotonated and was much weaker if the ligand was partly (or fully)
      protonated. A direct consequence of the model was the pH-dependent proton release
      upon complexation. (2) The retardation of transfer of electrons and protons to
      Q(B) was also strongly pH-dependent. The effect was large in the neutral pH range
      and decreased toward the acidic and alkaline pH values. (3) Steady-state turnover
      measurements indicated that the rate of the second proton transfer was much less
      inhibited than that of the first one, which became the rate-limiting step in
      continuous turnover of the RC. (4) Sodium azide partly recovered the proton
      transfer rate. The effect is not due to removal of the bound metal ion by azide
      but probably by formation of a proton-transporting azide network similarly as
      water molecules may build up proton pathways. (5) We argue that the inhibition
      comes mainly from pK(a) shifts of key protonatable residues that control the
      proton transfer along the H-bond network to Q(B). The electrostatic interaction
      between the metal ion and these residues may result in acidic pK(a) shifts
      between 1.5 and 2.0 that account for the observed retardation of the electron and
      proton transfer.

PMID- 11327849
TI  - Inhibition of the SHV-1 beta-lactamase by sulfones: crystallographic observation
      of two reaction intermediates with tazobactam.
AB  - Two species resulting from the reaction of the SHV-1 class A beta-lactamase with
      the sulfone inhibitor tazobactam have been trapped at 100 K and mapped by X-ray
      crystallography at 2.0 A resolution. An acyclic form of tazobactam is covalently
      bonded to the catalytic Ser70 side chain, and a second species, a five-atom vinyl
      carboxylic acid fragment of tazobactam, is bonded to Ser130. It is proposed that
      the electron density map of the crystal is a composite picture of two complexes,
      each with only a single bound species. It is estimated that the two complexes
      exist in the crystal in approximately equal populations. Results are discussed in
      relation to the mechanism-based inhibition of class A beta-lactamases by the
      similar inhibitors sulbactam and clavulanic acid.

PMID- 11327850
TI  - Proton involvement in the transition from the "peroxy" to the ferryl intermediate
      of cytochrome c oxidase.
AB  - In the absence of any external electron donor, the "peroxy" intermediate of
      cytochrome c oxidase (CcO-607) is converted to the ferryl form (CcO-580) and
      subsequently to oxidized enzyme. The rate of conversion of CcO-607 to the CcO-580
      form is pH dependent between pH 3.0 and pH 7.6. A plot of the logarithm of the
      rate constant for this conversion is a linear function of pH with a slope of 
      0.92, implying the involvement of a single proton in the transition. Upon rapidly
      lowering the pH from 8.1 to 5.8, the uptake of one proton was observed by direct
      pH measurement, and the kinetics of proton uptake coincide with the spectral
      conversion of CcO-607 to CcO-580. We interpret the slow endogenous decay of CcO
      607 to CcO-580 to be the result of proton transfer to a deprotonated group
      generated in the binuclear cavity during CcO-607 formation. This group is not
      freely accessible to protons from the medium, and its pK(a) is probably higher
      than 9.0.

PMID- 11327851
TI  - Intermodular communication in polyketide synthases: comparing the role of protein
      protein interactions to those in other multidomain proteins.
AB  - Although the role of protein-protein interactions in transducing signals within
      biological systems has been extensively explored, their relevance to the
      channeling of intermediates in metabolism is not widely appreciated. Polyketide
      synthases (PKSs) and nonribosomal peptide synthetases (NRPSs) are two related
      families of modular megasynthases that channel covalently bound intermediates
      from one active site to the next. Recent biochemical studies have highlighted the
      importance of protein-protein interactions in these chain transfer processes. The
      information available on this subject is reviewed, and its possible mechanistic
      implications are placed in context by comparisons with selected well-studied
      multicomponent protein systems.

PMID- 11327852
TI  - Selective protein-protein interactions direct channeling of intermediates between
      polyketide synthase modules.
AB  - Polyketide synthases (PKSs) have represented fertile targets for rational
      manipulation via protein engineering ever since their modular architecture was
      first recognized. However, the mechanistic principles by which biosynthetic
      intermediates are sequentially channeled between modules remain poorly
      understood. Here we demonstrate the importance of complementarity in a remarkably
      simple, repetitive structural motif within these megasynthases that has been
      implicated to affect intermodular chain transfer [Gokhale, R. S., et al. (1999)
      Science 284, 482]. The C- and N-terminal ends of adjacent PKS polypeptides are
      capped by short peptides of 20-40 residues. Mismatched sequences abolish
      intermodular chain transfer without affecting the activity of individual modules,
      whereas matched sequences can facilitate the channeling of intermediates between
      ordinarily nonconsecutive modules. Thus, in addition to substrate-PKS
      interactions and domain-domain interactions, these short interpolypeptide
      sequences represent a third determinant of selective chain transfer that must be
      taken into consideration in the protein engineering of PKSs. Preliminary
      biophysical studies on synthetic peptide mimics of these linkers suggest that
      they may adopt coiled-coil conformations.

PMID- 11327853
TI  - Near-infrared time-resolved optical absorption studies of the reaction of fully
      reduced cytochrome c oxidase with dioxygen.
AB  - Electron transfer during the reaction of fully reduced bovine heart cytochrome
      oxidase with dioxygen has been studied at 24 degrees C in the near-infrared
      region following photolysis of the fully reduced CO-bound complex. The transient
      spectral changes and kinetics were followed on microsecond to millisecond time
      scales at nine different wavelengths between 597 and 935 nm and were analyzed
      using singular value decomposition and global exponential fitting. Four apparent
      lifetimes, 14 micros, 40 micros, 86 micros, and 1.1 ms, were resolved. The near
      infrared spectra of the intermediates are extracted on the basis of a previously
      proposed mechanism [Sucheta et al. (1998) Biochemistry 37, 17905-17914] and
      compared to model spectra of the postulated intermediates. The data provide a
      comprehensive picture of the spectral contributions of the different redox
      centers in their respective oxidation or ligation states in the near-infrared
      region and strongly support that Cu(A) is partially (2/3), but not fully,
      oxidized in the 3-electron-reduced ferryl intermediate.

PMID- 11327854
TI  - A structural variation for MurB: X-ray crystal structure of Staphylococcus aureus
      UDP-N-acetylenolpyruvylglucosamine reductase (MurB).
AB  - The X-ray crystal structure of the substrate free form of Staphylococcus aureus
      UDP-N-acetylenolpyruvylglucosamine reductase (MurB) has been solved to 2.3 A
      resolution with an R-factor of 20.3% and a free R-factor of 22.3%. While the
      overall fold of the S. aureus enzyme is similar to that of the homologous
      Escherichia coli MurB X-ray crystal structure, notable distinctions between the
      S. aureus and E. coli MurB protein structures occur in residues involved in
      substrate binding. Analysis of available MurB sequences from other bacteria
      suggest that the S. aureus MurB structure is representative of a distinct
      structural class of UDP-N-acetylenolpyruvylglucosamine reductases including
      Bacillus subtilis and Helicobacter pylori that are characterized by a modified
      mechanism for substrate binding.

PMID- 11327855
TI  - Structures of the acyl-enzyme complexes of the Staphylococcus aureus beta
      lactamase mutant Glu166Asp:Asn170Gln with benzylpenicillin and cephaloridine.
AB  - The serine-beta-lactamases hydrolyze beta-lactam antibiotics in a reaction that
      proceeds via an acyl-enzyme intermediate. The double mutation, E166D:N170Q, of
      the class A enzyme from Staphylococcus aureus results in a protein incapable of
      deacylation. The crystal structure of this beta-lactamase, determined at 2.3 A
      resolution, shows that except for the mutation sites, the structure is very
      similar to that of the native protein. The crystal structures of two acyl-enzyme
      adducts, one with benzylpenicillin and the other with cephaloridine, have been
      determined at 1.76 and 1.86 A resolution, respectively. Both acyl-enzymes show
      similar key features, with the carbonyl carbon atom of the cleaved beta-lactam
      bond covalently bound to the side chain of the active site Ser70, and the
      carbonyl oxygen atom in an oxyanion hole. The thiadolizine ring of the cleaved
      penicillin is located in a slightly different position than the dihydrothiazine
      ring of cephaloridine. Consequently, the carboxylate moieties attached to the
      rings form different sets of interactions. The carboxylate group of
      benzylpenicillin interacts with the side chain of Gln237. The carboxylate group
      of cephaloridine is located between Arg244 and Lys234 side chains and also
      interacts with Ser235 hydroxyl group. The interactions of the cephaloridine
      resemble those seen in the structure of the acyl-enzyme of beta-lactamase from
      Escherichia coli with benzylpenicillin. The side chains attached to the cleaved
      beta-lactam rings of benzylpenicillin and cephaloridine are located in a similar
      position, which is different than the position observed in the E. coli
      benzylpenicillin acyl-enzyme complex. The three modes of binding do not show a
      trend that explains the preference for benzylpenicillin over cephaloridine in the
      class A beta-lactamases. Rather, the conformational variation arises because
      cleavage of the beta-lactam bond provides additional flexibility not available
      when the fused rings are intact. The structural information suggests that
      specificity is determined prior to the cleavage of the beta-lactam ring, when the
      rigid fused rings of benzylpenicillin and cephaloridine each form different
      interactions with the active site.

PMID- 11327857
TI  - Solution structures and integrin binding activities of an RGD peptide with two
      isomers.
AB  - The Arg-Gly-Asp (RGD) sequence serves as the primary integrin recognition site in
      extracellular matrix proteins, and peptides containing this sequence can mimic
      the activities of the matrix proteins. Depending on the context of the RGD
      sequence, an RGD-containing peptide may bind to all of the RGD-directed
      integrins, to a few, or to only a single one. We have previously isolated from a
      phage-displayed peptide library a cyclic peptide that binds avidly to the
      alpha(v)beta3 and alpha(v)beta5 integrins but does not bind to other closely
      related integrins. This peptide, ACDCRGDCFCG, exists in two natural
      configurations depending on internal disulfide bonding. The peptide with the 1-4;
      2-3 disulfide bond arrangement accounts for most of the alpha(v) integrin binding
      activity, whereas the 1-3; 2-4 peptide is about 10-fold less potent. Solution
      structure analysis by nuclear magnetic resonance reveals an entirely different
      presentation of the RGD motif in the two isomers of RGD-4C. These results provide
      new insight into the ligand recognition specificity of integrins.

PMID- 11327856
TI  - Active site of chondroitin AC lyase revealed by the structure of enzyme
      oligosaccharide complexes and mutagenesis.
AB  - The crystal structures of Flavobacterium heparinium chondroitin AC lyase
      (chondroitinase AC; EC 4.2.2.5) bound to dermatan sulfate hexasaccharide
      (DS(hexa)), tetrasaccharide (DS(tetra)), and hyaluronic acid tetrasaccharide
      (HA(tetra)) have been refined at 2.0, 2.0, and 2.1 A resolution, respectively.
      The structure of the Tyr234Phe mutant of AC lyase bound to a chondroitin sulfate
      tetrasaccharide (CS(tetra)) has also been determined to 2.3 A resolution. For
      each of these complexes, four (DS(hexa) and CS(tetra)) or two (DS(tetra) and
      HA(tetra)) ordered sugars are visible in electron density maps. The lyase AC
      DS(hexa) and CS(tetra) complexes reveal binding at four subsites, -2, -1, +1, and
      +2, within a narrow and shallow protein channel. We suggest that subsites -2 and 
      1 together represent the substrate recognition area, +1 is the catalytic subsite
      and +1 and +2 together represent the product release area. The putative catalytic
      site is located between the substrate recognition area and the product release
      area, carrying out catalysis at the +1 subsite. Four residues near the catalytic
      site, His225, Tyr234, Arg288, and Glu371 together form a catalytic tetrad. The
      mutations His225Ala, Tyr234Phe, Arg288Ala, and Arg292Ala, revealed residual
      activity for only the Arg292Ala mutant. Structural data indicate that Arg292 is
      primarily involved in recognition of the N-acetyl and sulfate moieties of
      galactosamine, but does not participate directly in catalysis. Candidates for the
      general base, removing the proton attached to C-5 of the glucuronic acid at the
      +1 subsite, are Tyr234, which could be transiently deprotonated during catalysis,
      or His225. Tyrosine 234 is a candidate to protonate the leaving group. Arginine
      288 likely contributes to charge neutralization and stabilization of the enolate
      anion intermediate during catalysis.

PMID- 11327858
TI  - Solution structure of the p53 regulatory domain of the p19Arf tumor suppressor
      protein.
AB  - Arf is a tumor suppressor that regulates p53 function and is a frequent target
      for loss in human cancers. Through two novel mechanisms, Arf inhibits the
      oncoprotein Hdm2, a negative regulator of p53. (1) Arf inhibits the E3 ubiquitin
      ligase activity of Hdm2 that leads to p53 degradation, and (2) Arf sequesters
      Hdm2 within nucleoli. These activities of Arf promote p53-mediated cell cycle
      arrest and apoptosis. Fundamental to these processes are interactions between Arf
      and Hdm2. Here we show that a peptide containing the 37 N-terminal amino acids of
      mouse Arf (mArfN37) localizes to nucleoli, sequesters Hdm2 within nucleoli, and
      causes cell cycle arrest. Circular dichroism and NMR spectroscopy show that
      mArfN37 is largely unstructured under aqueous conditions; however, the peptide
      adopts two alpha-helices (helix 1, residues 4-14; and helix 2, residues 20-29) in
      2,2,2-trifluoroethanol (TFE). Each helix contains an amino acid motif that is
      repeated twice in mArfN37, once in each helix. The two helices, however, do not
      interact but are connected by an apparently flexible linker. The repeated motif
      contains Arg residues spaced by a hydrophobic segment that may be involved in
      Hdm2 recognition and binding. The RRPR nucleolar localization signal, contained
      within residues 31-34, appears to be disordered under all conditions. The
      identification of two Arf structural modules suggests that short peptides
      containing the repeated motif may function as Arf mimics and may allow the design
      of small molecule Arf mimics in the future.

PMID- 11327859
TI  - Solution structure of the ribosome recycling factor from Aquifex aeolicus.
AB  - The solution structure of ribosome recycling factor (RRF) from hyperthermophilic
      bacterium, Aquifex aeolicus, was determined by heteronuclear multidimensional NMR
      spectroscopy. Fifteen structures were calculated using restraints derived from
      NOE, J-coupling, and T1/T2 anisotropies. The resulting structure has an overall L
      shaped conformation with two domains and is similar to that of a tRNA molecule.
      The domain I (corresponding to the anticodon stem of tRNA) is a rigid three alpha
      helix bundle. Being slightly different from usual coiled-coil arrangements, each
      helix of domain I is not twisted but straight and parallel to the main axis. The
      domain II (corresponding to the portion with the CCA end of tRNA) is an
      alpha/beta domain with an alpha-helix and two beta-sheets, that has some flexible
      regions. The backbone atomic root-mean-square deviation (rmsd) values of both
      domains were 0.7 A when calculated separately, which is smaller than that of the
      molecule as a whole (1.4 A). Measurement of 15N-[1H] NOE values show that the
      residues in the corner of the L-shaped molecule are undergoing fast internal
      motion. These results indicate that the joint region between two domains
      contributes to the fluctuation in the orientation of two domains. Thus, it was
      shown that RRF remains the tRNA mimicry in solution where it functions.

PMID- 11327860
TI  - ENDOR structural characterization of a catalytically competent acylenzyme
      reaction intermediate of wild-type TEM-1 beta-lactamase confirms glutamate-166 as
      the base catalyst.
AB  - The catalytically competent active-site structure of a true acylenzyme reaction
      intermediate of TEM-1 beta-lactamase formed with the kinetically specific spin
      labeled substrate 6-N-(2,2,5,5-tetramethyl-1-oxypyrrolinyl-3-carboxyl)
      penicillanic acid isolated under cryoenzymologic conditions has been determined
      by angle-selected electron nuclear double resonance (ENDOR) spectroscopy.
      Cryoenzymologic experiments with use of the chromophoric substrate 6-N-[3-(2
      furanyl)-propen-2-oyl]-penicillanic acid showed that the acylenzyme reaction
      intermediate could be stabilized in the -35 to -75 degrees C range with a half
      life suitably long to allow freeze-quenching of the reaction species for ENDOR
      studies while a noncovalent Michaelis complex could be optically identified at
      temperatures only below -70 degrees C. The wild-type, Glu166Asn, Glu240Cys, and
      Met272Cys mutant forms of the mature enzyme were overexpressed in perdeuterated
      minimal medium to allow detection and assignment of proton resonances specific
      for the substrate and chemically modified amino acid residues in the active site.
      From analysis of the dependence of the ENDOR spectra on the setting of the static
      laboratory magnetic field H0, the dipolar contributions to the principal
      hyperfine coupling components were estimated to calculate the separations between
      the unpaired electron of the nitroxyl group and isotopically identified nuclei.
      These electron-nucleus distances were applied as constraints to assign the
      conformation of the substrate in the active site and of amino acid side chains by
      molecular modeling. Of special interest was that the ENDOR spectra revealed a
      water molecule sequestered in the active site of the acylenzyme of the wild-type
      protein that was not detected in the deacylation impaired Glu166Asn mutant. On
      the basis of the X-ray structure of the enzyme, the ENDOR distance constraints
      placed this water molecule within hydrogen-bonding distance to the carboxylate
      side chain of glutamate-166 as if it were poised for nucleophilic attack of the
      scissile ester bond. The ENDOR results provide experimental evidence of glutamate
      166 in its functional role as the general base catalyst in the wild-type enzyme
      for hydrolytic breakdown of the acylenzyme reaction intermediate of TEM-1 beta
      lactamase.

PMID- 11327861
TI  - The role of active site residue arginine 218 in firefly luciferase
      bioluminescence.
AB  - Firefly luciferase catalyzes the highly efficient emission of yellow-green light
      from substrate firefly luciferin by a sequence of reactions that require Mg-ATP
      and molecular oxygen. We had previously developed a working model of the
      luciferase active site based on the X-ray structure of the enzyme without bound
      substrates. In our model, the side chain guanidinium group of Arg218 appears to
      be located in close proximity to the substrate's hydroxyl group at the bottom of
      the luciferin binding pocket. A similar role for Arg337 also has been proposed.
      We report here the construction, purification, and characterization of mutant
      luciferases R218A, R218Q, R218K, R337Q, and R337K. Alteration of the Arg218 side
      chain produced enzymes with 15-20-fold increases in the Km values for luciferin.
      The contrasting near-normal Km values for luciferin determined with the Arg337
      enzymes support our proposal that Arg218 (and not Arg337) is an essential
      luciferin binding site residue. Bioluminescence emission studies indicated that
      in the absence of a positively charged group at position 218, red bioluminescence
      was produced. Based on this result and those of additional fluorescence
      experiments, we speculate that Arg218 maintains the polarity and rigidity of the
      emitter binding site necessary for the normal yellow-green emission of P. pyralis
      luciferase. The findings reported here are interpreted in the context of the
      firefly luciferase X-ray structures and computational-based models of the active
      site.

PMID- 11327862
TI  - Site-specific cation binding mediates TATA binding protein-DNA interaction from a
      hyperthermophilic archaeon.
AB  - Pyrococcus woesei (Pw) is a hyperthermophilic archaeal organism that exists under
      conditions of high salt and elevated temperature. In a previous study [O'Brien,
      R., DeDecker, B., Fleming, K., Sigler, P. B., and Ladbury, J. E., (1998) J. Mol.
      Biol. 279, 117-125], we showed that, despite the similarity of primary and
      secondary structure, the TATA box binding protein (TBP) from Pw binds
      thermodynamically in a fundamentally different way to its mesophilic
      counterparts. The affinity of the interaction increases as the salt concentration
      is increased. The formation of the protein-DNA complex involves the release of
      water and the uptake of ions, which were hypothesized to be cations. Here we test
      this hypothesis by selecting potential cation binding sites at negatively
      charged, acidic residues in the complex interface. These were substituted using
      site-directed mutagenesis of specific residues. Changes in the thermodynamic
      parameters on formation of the mutant protein-DNA complex were determined using
      isothermal titration calorimetry and compared to the wild type interaction.
      Removal of a glutamate residue from the binding site resulted in the uptake of
      one less cation on formation of the complex. This glutamate (E12) is directly
      involved in the binding of cations in the complex interface. Substitution of
      another acidic residue proximal to the DNA binding site (D101) had no effect on
      cation uptake, suggesting that the location of the amino acid on the protein
      surface is important in dictating the potential to coordinate cations. Removal of
      the cation binding site provided a more favorable entropy of binding; however,
      this effect is significantly reduced at higher salt concentrations. The removal
      of the cation binding site led to an increase in affinity with respect to the
      wild-type TBP at low salt concentrations.

PMID- 11327863
TI  - TRF1 inhibits telomere C-strand DNA synthesis in vitro.
AB  - Human TTAGGG repeat-binding factor 1 (TRF1) is involved in the regulation of
      telomere length in vivo, but the mechanism of regulation remains largely
      undefined. We have developed an in vitro system for assessing the effect of TRF1
      on DNA synthesis using purified proteins and synthetic DNA substrates. Results
      reveal that TRF1, when bound to telomeric duplex DNA, inhibits DNA synthesis
      catalyzed by DNA polymerase alpha/primase (pol alpha). Inhibition required that
      TRF1 be bound to duplex telomeric DNA as no effect of TRF1 was observed on
      nontelomeric, random DNA substrates. Inhibition was shown to be dependent on TRF1
      concentration and the length of the telomeric duplex region of the DNA substrate.
      When bound in cis to telomeric duplex DNA, TRF1 was also capable of inhibiting
      pol alpha-catalyzed DNA synthesis on nontelomeric DNA sequences from positions
      both upstream and downstream of the extending polymerase. Inhibition of DNA
      synthesis was shown to be specific for TRF1 but not necessarily for the DNA
      polymerase used in the extension reaction. In a series of control experiments, we
      assessed T7 DNA polymerase-catalyzed synthesis on a DNA template containing
      tandem gal4 operators. In these experiments, the addition of the purified Gal4
      DNA binding domain (Gal4-DBD) protein has no effect on the ability of T7
      polymerase to copy the DNA template. Interestingly, TRF1 inhibition was observed
      on telomeric DNA substrates using T7 DNA polymerase. These results suggest that
      TRF1, when bound to duplex telomeric DNA, serves to block extension by DNA
      polymerases. These results are discussed with respect to the role of TRF1 in
      telomere length regulation.

PMID- 11327864
TI  - In vivo recognition of an RNA aptamer by its transcription factor target.
AB  - In vitro-selected RNA aptamers are potential inhibitors of disease-related
      macromolecules. Our laboratory previously isolated an RNA aptamer that
      specifically binds to the human transcription factor NF-kappaB. This RNA aptamer
      competitively inhibits DNA binding by NF-kappaB in vitro. In the study presented
      here, this aptamer was tested for binding to the p50 homodimer form of NF-kappaB
      (p50(2)) in eukaryotic cells using a yeast three-hybrid system. We show that the
      alpha-p50 RNA aptamer selectively binds recombinant p50(2) expressed in yeast,
      demonstrating in vivo recognition of an in vitro-selected RNA aptamer by its
      protein target. This result suggests that RNA decoys might be used to inhibit the
      function of DNA-binding proteins in vivo.

PMID- 11327865
TI  - Correlation of low-barrier hydrogen bonding and oxyanion binding in transition
      state analogue complexes of chymotrypsin.
AB  - The structures of the hemiketal adducts of Ser 195 in chymotrypsin with N-acetyl
      L-leucyl-L-phenylalanyl trifluoromethyl ketone (AcLF-CF3) and N-acetyl-L
      phenylalanyl trifluoromethyl ketone (AcF-CF3) were determined to 1.4-1.5 A by X
      ray crystallography. The structures confirm those previously reported at 1.8-2.1
      A [Brady, K., Wei, A., Ringe, D., and Abeles, R. H. (1990) Biochemistry 29, 7600
      7607]. The 2.6 A spacings between Ndelta1 of His 57 and Odelta1 of Asp 102 are
      confirmed at 1.3 A resolution, consistent with the low-barrier hydrogen bonds
      (LBHBs) between His 57 and Asp 102 postulated on the basis of spectroscopy and
      deuterium isotope effects. The X-ray crystal structure of the hemiacetal adduct
      between Ser 195 of chymotrypsin and N-acetyl-L-leucyl-L-phenylalanal (AcLF-CHO)
      has also been determined at pH 7.0. The structure is similar to the AcLF-CF3
      adduct, except for the presence of two epimeric adducts in the R- and S
      configurations at the hemiacetal carbons. In the (R)-hemiacetal, oxygen is
      hydrogen bonded to His 57, not the oxyanion site. On the basis of the downfield
      1H NMR spectrum in solution, His 57 is not protonated at Nepsilon2, and there is
      no LBHB at pH >7.0. Because addition of AcLF-CHO to chymotrypsin neither releases
      nor takes up a proton from solution, it is concluded that the hemiacetal oxygen
      of the chymotrypsin-AcLF-CHO complex is a hydroxyl group and not attracted to the
      oxyanion site. The protonation states of the hemiacetal and His 57 are explained
      by the high basicity of the hemiacetal oxygen (pK(a) > 13.5) relative to that of
      His 57. The 13C NMR signal for the adduct of AcLF-13CHO with chymotrypsin is
      consistent with a neutral hemiacetal between pH 7 and 13. At pH <7.0, His 57 in
      the AcLF-CHO-hemiacetal complex of chymotrypsin undergoes protonation at
      Nepsilon2 of His 57, leading to a transition of the 15.1 ppm downfield signal to
      17.8 ppm. The pK(a)s in the active sites of the AcLF-CF3 and AcLF-CHO adducts
      suggest an energy barrier of 6-7 kcal x mol(-1) against ionizations that change
      the electrostatic charge at the active site. However, ionizations of neutral His
      57 in the AcLF-CHO-chymotrypsin adduct, or in free chymotrypsin, proceed with no
      apparent barrier. Protonation of His 57 is accompanied by LBHB formation,
      suggesting that stabilization by the LBHB overcomes the barrier to ionization. On
      the basis of the hydration constant for AcLF-13CHO and its inhibition constant,
      its K(d) is 16 microM, 8000-fold larger than the comparable value for AcLF-CF3.

PMID- 11327866
TI  - Kinetic properties of chitinase-1 from the fungal pathogen Coccidioides immitis.
AB  - The endochitinase from Coccidioides immitis (CiX1) is a member of the class 18
      chitinase family. Here we show the enzyme functions by a retaining catalytic
      mechanism; that is, the beta-conformation of the chitin substrate linkages is
      preserved after hydrolysis. The pattern of cleavage of N-acetyglucosamine
      (GlcNAc) oligosaccharide substrates has been determined. (GlcNAc)6 is
      predominantly cleaved into (GlcNAc)2 and (GlcNAc)4, where the (GlcNAc)2 group
      arises from the nonreducing end of the substrate and is formed as the beta
      anomer. With time, transglycosylation occurs, generating (GlcNAc)8 from the
      product dimer and fresh hexamer. Similar patterns are seen for the cleavage of
      (GlcNAc)5 and (GlcNAc)4 where dimers cleaved from the nonreducing end reflect the
      most common binding and hydrolysis pattern. Intrinsic fluorescence measurements
      suggest the dissociation constant for (GlcNAc)4 is 50 microM. Synthetic
      substrates with fluorescent leaving groups exhibit complicated profiles in the
      relationship between initial velocity and substrate concentration, making it
      difficult to obtain the values of kinetic constants. An improved theoretical
      analysis of the time-course of (GlcNAc)6 degradation allows the unitary free
      energy of binding of the individual subsites of the enzyme to be estimated. The
      free energy values obtained are consistent with the dissociation constant
      obtained by fluorescence measurements, and generate a model of substrate
      interaction that can be tested against the crystal structure of the enzyme.

PMID- 11327867
TI  - Dimeric pig heart succinate-coenzyme A transferase uses only one subunit to
      support catalysis.
AB  - Pig heart succinate-coenzyme A transferase (succinyl-coenzyme A: 3-oxoacid
      coenzyme A transferase; E. C. 2.8.3.5.), a dimeric enzyme purified by affinity
      chromatography on Procion Blue MX-2G Sepharose, reacts with acetoacetyl-coenzyme
      A to form a covalent enzyme-coenzyme A thiolester intermediate in which the
      active site glutamate (E344) of both subunits each forms thiolester links with
      coenzyme A. Reaction of this dimeric enzyme-coenzyme A species with sodium
      borohydride leads to inactivation of the enzyme and reduction of the thiolester
      on both subunits to the corresponding enzyme alcohol, as judged by electrospray
      mass spectrometry. Reaction of the dimeric enzyme-coenzyme A intermediate with
      either succinate or acetoacetate, however, results in only one-half of the
      coenzyme A being transferred to the acceptor carboxylate to form either succinyl
      coenzyme A or acetoacetyl-coenzyme A. Reaction of this latter enzyme species with
      borohydride caused no loss of enzyme activity despite the reduction of the
      remaining half of the enzyme-coenzyme A thiolester to the enzyme alcohol. That
      this catalytic asymmetry existed between subunits within the same enzyme dimer
      was demonstrated by showing that the enzyme species, created by successive
      reaction with acetoacetyl-coenzyme A and succinate, bound to Blue MX-2G Sepharose
      through the remaining available active site and could be eluted as a single
      chromatographic species by succinyl-coenzyme A. It is concluded that while both
      of the subunits of the succinate-coenzyme A transferase dimer are able to form
      enzyme-coenzyme A thiolester intermediates, only one subunit is competent to
      transfer the coenzyme A moiety to a carboxylic acid acceptor to form the new acyl
      coenzyme A product. The possible structural basis for this catalytic asymmetry
      and its mechanistic implications are discussed.

PMID- 11327868
TI  - Evidence for synergy between family 2b carbohydrate binding modules in
      Cellulomonas fimi xylanase 11A.
AB  - Glycoside hydrolases often contain multiple copies of noncatalytic carbohydrate
      binding modules (CBMs) from the same or different families. Currently, the
      functional importance of this complex molecular architecture is unclear. To
      investigate the role of multiple CBMs in plant cell wall hydrolases, we have
      determined the polysaccharide binding properties of wild type and various
      derivatives of Cellulomonas fimi xylanase 11A (Cf Xyn11A). This protein, which
      binds to both cellulose and xylan, contains two family 2b CBMs that exhibit 70%
      sequence identity, one internal (CBM2b-1), which has previously been shown to
      bind specifically to xylan and the other at the C-terminus (CBM2b-2). Biochemical
      characterization of CBM2b-2 showed that the module bound to insoluble and soluble
      oat spelt xylan and xylohexaose with K(a) values of 5.6 x 10(4), 1.2 x 10(4), and
      4.8 x 10(3) M(-1), respectively, but exhibited extremely weak affinity for
      cellohexaose (<10(2) M(-1)), and its interaction with insoluble cellulose was too
      weak to quantify. The CBM did not interact with soluble forms of other plant cell
      wall polysaccharides. The three-dimensional structure of CBM2b-2 was determined
      by NMR spectroscopy. The module has a twisted "beta-sandwich" architecture, and
      the two surface exposed tryptophans, Trp 570 and Trp 602, which are in a
      perpendicular orientation with each other, were shown to be essential for ligand
      binding. In addition, changing Arg 573 to glycine altered the polysaccharide
      binding specificity of the module from xylan to cellulose. These data demonstrate
      that the biochemical properties and tertiary structure of CBM2b-2 and CBM2b-1 are
      extremely similar. When CBM2b-1 and CBM2b-2 were incorporated into a single
      polypeptide chain, either in the full-length enzyme or an artificial construct
      comprising both CBM2bs covalently joined via a flexible linker, there was an
      approximate 18-20-fold increase in the affinity of the protein for soluble and
      insoluble xylan, as compared to the individual modules, and a measurable
      interaction with insoluble acid-swollen cellulose, although the K(a)
      (approximately 6.0 x 10(4) M(-1)) was still much lower than for insoluble xylan
      (K(a) = approximately 1.0 x 10(6) M(-1)). These data demonstrate that the two
      family 2b CBMs of Cf Xyn11A act in synergy to bind acid swollen cellulose and
      xylan. We propose that the increased affinity of glycoside hydrolases for
      polysaccharides, through the synergistic interactions of CBMs, provides an
      explanation for the duplication of CBMs from the same family in some prokaryotic
      cellulases and xylanases.

PMID- 11327869
TI  - Thermodynamics of RNA internal loops with a guanosine-guanosine pair adjacent to
      another noncanonical pair.
AB  - Thermodynamic parameters measured by optical melting are reported for formation
      of RNA duplexes containing tandem noncanonical pairs with at least one guanosine
      guanosine (GG) pair. For selected sequences, imino proton NMR provides evidence
      that the desired duplex forms and that the structure of a GG pair adjacent to a
      noncanonical pair depends on context. A GG pair next to a different noncanonical
      pair is more stable than expected from measurements of adjacent GG pairs. This is
      likely due to an unfavorable stacking interaction between adjacent GG pairs,
      where areas of high negative charge probably overlap. The results suggest a model
      where tandem noncanonical pairs closed by two GC pairs are assigned the following
      free energy increments at 37 degrees C: 0.8 kcal/mol for adjacent GG pairs, 1.0
      kcal/mol for GG next to UU, and -0.3 kcal/mol for all others. These values are
      adjusted by 0.65 kcal/mol for each closing AU pair.

PMID- 11327870
TI  - Binding and recognition of GATATC target sequences by the EcoRV restriction
      endonuclease: a study using fluorescent oligonucleotides and fluorescence
      polarization.
AB  - Oligonucleotides labeled with hexachlorofluorescein (hex) have enabled the
      interaction of the restriction endonuclease EcoRV with DNA to be evaluated using
      fluorescence anisotropy. The sensitivity of hex allowed measurements at
      oligonucleotide concentrations as low as 1 nM, enabling K(D) values in the low
      nanomolar range to be measured. Both direct titration, i.e., addition of
      increasing amounts of the endonuclease to hex-labeled oligonucleotides, and
      displacement titration, i.e., addition of unlabeled oligonucleotide to preformed
      hex-oligonucleotide/EcoRV endonuclease complexes, have been used for K(D)
      determination. Displacement titration is the method of choice; artifacts due to
      any direct interaction of the enzyme with the dye are eliminated, and higher
      fluorescent-labeled oligonucleotide concentrations may be used, improving signal
      to-noise ratio. Using this approach (with three different oligonucleotides) we
      found that the EcoRV restriction endonuclease showed a preference of between 1.5
      and 6.5 for its GATATC target sequence at pH 7.5 and 100 mM NaCl, when the
      divalent cation Ca2+ is absent. As expected, both the presence of Ca2+ and a
      decrease in pH value stimulated the binding of specific sequences but had much
      less effect on nonspecific ones.

PMID- 11327871
TI  - Individual determination of the yield of the main UV-induced dimeric pyrimidine
      photoproducts in DNA suggests a high mutagenicity of CC photolesions.
AB  - Bipyrimidine photoproducts induced in DNA by UVB radiation include cyclobutane
      dimers, (6-4) photoproducts, and their related Dewar valence isomers. Even though
      these lesions have been extensively studied, their rate of formation within DNA
      is still not known for each possible bipyrimidine site (TT, TC, CT, and CC).
      Using a method based on the coupling of liquid chromatography to mass
      spectrometry, we determined the distribution of the 12 possible bipyrimidine
      photoproducts within isolated and cellular DNA. TT and TC were found to be the
      most photoreactive sequences, whereas lower amounts of damage were produced at CT
      and CC sites. In addition to this quantitative aspect, sequence effects were
      observed on the relative yield of (6-4) adducts with respect to cyclobutane
      pyrimidine dimers. Another interesting result is the lack of formation of Dewar
      valence isomers in detectable amounts within the DNA of cells exposed to low
      doses of UVB radiation. The photoproduct distribution obtained does not fully
      correlate with the UV mutation spectrum. A major striking observation deals with
      the low yield of cytosine-cytosine photoproducts which are likely to be
      associated with the UV-specific CC to TT tandem mutation.

PMID- 11327872
TI  - Red fluorescent protein from Discosoma as a fusion tag and a partner for
      fluorescence resonance energy transfer.
AB  - The biochemical and biophysical properties of a red fluorescent protein from a
      Discosoma species (DsRed) were investigated. The recombinant DsRed expressed in
      E. coli showed a complex absorption spectrum that peaked at 277, 335, 487, 530,
      and 558 nm. Excitation at each of the absorption peaks produced a main emission
      peak at 583 nm, whereas a subsidiary emission peak at 500 nm appeared with
      excitation only at 277 or 487 nm. Incubation of E. coli or the protein at 37
      degrees C facilitated the maturation of DsRed, resulting in the loss of the 500
      nm peak and the enhancement of the 583-nm peak. In contrast, the 500-nm peak
      predominated in a mutant DsRed containing two amino acid substitutions
      (Y120H/K168R). Light-scattering analysis revealed that DsRed proteins expressed
      in E. coli and HeLa cells form a stable tetramer complex. DsRed in HeLa cells
      grown at 37 degrees C emitted predominantly at 583 nm. The red fluorescence was
      imaged using a two-photon laser (Nd:YLF, 1047 nm) as well as a one-photon laser
      (He:Ne, 543.5 nm). When fused to calmodulin, the red fluorescence produced an
      aggregation pattern only in the cytosol, which does not reflect the distribution
      of calmodulin. Despite the above spectral and structural complexity, fluorescence
      resonance energy transfer (FRET) between Aequorea green fluorescent protein (GFP)
      variants and DsRed was achieved. Dynamic changes in cytosolic free Ca2+
      concentrations were observed with red cameleons containing yellow fluorescent
      protein (YFP), cyan fluorescent protein (CFP), or Sapphire as the donor and RFP
      as the acceptor, using conventional microscopy and one- or two-photon excitation
      laser scanning microscopy. Particularly, the use of the Sapphire-DsRed pair
      rendered the red cameleon tolerant of acidosis occurring in hippocampal neurons,
      because both Sapphire and DsRed are extremely pH-resistant.

PMID- 11327873
TI  - Evaluation of the influence of compound structure on stacked-dimer formation in
      the DNA minor groove.
AB  - The Human Genome Project as well as sequencing of the genomes of other organisms
      offers a wealth of DNA targets for both therapeutic and diagnostic applications,
      and it is important to develop additional DNA binding motifs to fully exploit the
      potential of this new information. We have recently found that an aromatic
      dication, DB293, with an amidine-phenyl-furan-benzimidazole-amidine structure can
      recognize specific sequences of DNA by binding in the minor groove as a dimer
      [Wang, L., Bailly, C., Kumar, A., Ding, D., Bajic, M., Boykin, D. W., and Wilson,
      W. D. (2000) Proc. Natl. Acad. Sci. U.S.A. 97, 12-16]. The dimer binding is
      strong, highly cooperative and, in contrast to many closely related heterocyclic
      dications, has both GC and AT base pairs in the minor groove binding site. The
      aromatic heterocycle stacked dimer is quite different in structure from the
      polyamide-lexitropsin type compounds, and it is a dication while all lexitropsin
      dimers are monocations. The heterocyclic dimer represents only the second small
      molecule class that can recognize mixed sequences of DNA. To test the structural
      limits on the new type of complex, it is important to probe the influence of
      compound charge, chemical groups, and structural features. The effects of these
      compound molecular variations on DNA complex formation with several DNA sequences
      were evaluated by DNase I footprinting, CD and UV spectroscopy, thermal melting,
      and quantitative analysis with surface plasmon resonance biosensor methods.
      Conversion of the amidines to guanidinium groups does permit the cooperative
      dimer to form but removal of one amidine or addition of an alkyl group to the
      amidine strongly inhibited dimer formation. Changing the phenyl of DB293 to a
      benzimidazole or the benzimidazole to a phenyl or benzofuran also inhibited dimer
      formation. The results show that formation of the minor groove stacked-dimer
      complex is very sensitive to compound structure. The discovery of the aromatic
      dimer mode offers new opportunities to enhance the specificity and expand the
      range of applications of the compounds that target DNA.

PMID- 11327874
TI  - Tyrosine Raman signatures of the filamentous virus Ff are diagnostic of non
      hydrogen-bonded phenoxyls: demonstration by Raman and infrared spectroscopy of p
      cresol vapor.
AB  - p-Cresol is a simple molecular model for the para phenolic side chain of
      tyrosine. Previously, Siamwiza and co-workers [(1975) Biochemistry 14, 4870-4876]
      investigated p-cresol solutions to identify Raman spectroscopic signatures for
      different hydrogen-bonding states of the tyrosine phenoxyl group in proteins.
      They found that the phenolic moiety exhibits an intense Raman doublet in the
      spectral interval 820-860 cm(-1) and that the doublet intensity ratio (I2/I1,
      where I2 and I1 are Raman peak intensities of the higher- and lower-wavenumber
      members of the doublet) is diagnostic of specific donor and acceptor roles of the
      phenoxyl OH group. The range of the doublet intensity ratio in proteins (0.30 <
      I2/I1 < 2.5) was shown to be governed by Fermi coupling between the phenolic ring
      stretching fundamental nu1 and the first overtone of the phenolic ring
      deformation mode nu(16a), such that when the tyrosine phenoxyl proton is a strong
      hydrogen-bond donor, I2/I1 = 0.30, and when the tyrosine phenoxyl oxygen is a
      strong hydrogen-bond acceptor, I2/I1 = 2.5. Here, we interpret the Raman and
      infrared spectra of p-cresol vapor and extend the previous correlation to the non
      hydrogen-bonded state of the tyrosine phenoxyl group. In the absence of hydrogen
      bonding, the Raman intensity of the higher-wavenumber component of the canonical
      Fermi doublet is greatly enhanced such that I2/I1 = 6.7. Thus, for the non
      hydrogen-bonded phenoxyl, the lower-wavenumber member of the Fermi doublet loses
      most of its Raman intensity. This finding provides a basis for understanding the
      anomalous Raman singlet signature (approximately 854 cm(-1)) observed for
      tyrosine in coat protein subunits of filamentous viruses Ff and Pf1 [Overman, S.
      A., et al. (1994) Biochemistry 33, 1037-1042; Wen, Z. Q., et al. (1999)
      Biochemistry 38, 3148-3156]. The implications of the present results for Raman
      analysis of tyrosine hydrogen-bonding states in other proteins are considered.

PMID- 11327875
TI  - Photoaffinity labeling of mutant neurokinin-1 receptors reveals additional
      structural features of the substance P/NK-1 receptor complex.
AB  - Photoaffinity labeling, receptor site-directed mutagenesis, and high-resolution
      NMR spectroscopy have been combined to further define the molecular details of
      the binding of substance P (SP) to the rat neurokinin-1 (NK-1) receptor. Mutant
      NK-1 receptors were constructed by substituting Ala for Met174 and/or Met181:
      residues previously identified as the sites of covalent attachment of
      radioiodinated, photoreactive derivatives of SP containing p-benzoyl-L
      phenylalanine (Bpa) in positions 4 and 8, respectively. Photoaffinity labeling of
      the M181A mutant using radioiodinated Bpa8-SP resulted in a marked reduction in
      photoincorporation efficiency compared to the wild-type receptor. In contrast,
      photoaffinity labeling of the M174A mutant using radioiodinated Bpa4-SP gave the
      unexpected result of an increase in the efficiency of photoincorporation compared
      to the wild-type receptor. Enzymatic and chemical fragmentation analysis of the
      photolabeled receptor mutants established that the sites of covalent attachment
      were not the substituted alanine, but rather the other methionine on the second
      extracellular (E2) loop sequence, that is not the primary site of attachment in
      the wild-type receptor. The results thus suggest a close spatial relationship
      between Met174 and Met181 on the NK-1 receptor. To evaluate this structural
      disposition, NMR analyses were performed on a synthetic peptide with a sequence
      corresponding to the entire E2 loop and segments of the adjoining transmembrane
      helices to anchor the peptide in the lipids used to mimic a membrane. The
      structural features of the E2 loop include a centrally located alpha-helix,
      extending from Pro175 to Glu183, as well as smaller alpha-helices at the termini,
      corresponding to the transmembrane regions. The two methionine residues are
      located on the same face of the central alpha-helix, approximately 11 A apart
      from each other, and are therefore consistent with the conclusions of the
      photoaffinity labeling results.

PMID- 11327876
TI  - Role of alpha-helix seven of Bacillus thuringiensis Cry1Ab delta-endotoxin in
      membrane insertion, structural stability, and ion channel activity.
AB  - Domain I of the Cry1Ab insecticidal toxic protein has seven alpha-helices and is
      considered to be involved in the ion channel activity. While other alpha-helices,
      particularly alpha-4 and alpha-5, have been extensively explored, the remaining
      alpha-helices have been slightly studied. Site-directed mutagenesis was used to
      generate mutations throughout sequences encoding the alpha-helix 7 to test its
      role in ion channel function. Every amino acid residue in alpha-helix 7 was
      mutated to alanine. Most resultant proteins, e.g., D225A, W226A, Y229A, N230A,
      R233A, R234A, D242A, and F247A yielded no protoxin or were sensitive to
      degradation by trypsin or Manduca sexta midgut juice. Other mutant proteins,
      R224A, R228A, and E235A, were resistant to degradation to the above proteases but
      were 8, 30, and 12 times less toxic to M. sexta, respectively, than the wild-type
      Cry1Ab. Circular dichroism spectroscopy indicated a very small change in the
      R228A spectrum, while R224A and E235A display the same spectrum as the wild-type
      protein. These three mutant proteins showed little differences from Cry1Ab when
      analyzed by saturation binding and competition binding kinetics with (125)I
      labeled toxin or by surface plasmon resonance to M. sexta brush border membrane
      vesicles. More conservative amino acid substitutions were introduced into alpha
      helix 7 residues: R228K, F232Y, E235Q, and F247Y. In comparison with wild-type
      Cry1Ab, mutant proteins R228K, F232Y, E235A, and E235Q selectively discriminate
      between K+ and Rb+, while R224A and R228A had reduced inhibition of short-circuit
      current for both ions, when analyzed by voltage clamping of M. sexta midguts.

PMID- 11327877
TI  - Vulnerability of synaptosomes from apoE knock-out mice to structural and
      oxidative modifications induced by A beta(1-40): implications for Alzheimer's
      disease.
AB  - Apolipoprotein E (apoE) plays an important role in the response to central
      nervous system injury. The e4 allele of apoE and amyloid beta-peptide (Abeta) are
      associated with Alzheimer's disease (AD) and may be central to the pathogenesis
      of this disorder. Recent studies demonstrate evidence for neurodegeneration and
      increased lipid peroxidation in transgenic mice lacking apoE (KO). In the current
      study, synaptosomes were prepared from apoE KO mice to determine the role of apoE
      in synaptic membrane structure and to determine susceptibility to oxidative
      damage by Abeta(1-40). ApoE KO mice exhibited structural modifications to lipid
      and protein components of synaptosomal membranes as determined by electron
      paramagnetic resonance in conjunction with lipid- and protein- specific spin
      labels. Incubation with 5 microM Abeta(1-40) resulted in more severe oxidative
      modifications to proteins and lipids in apoE KO synaptosomes as measured by
      protein carbonyls, an index of protein oxidation, and TBARs and protein-bound 4
      hydroxynonenal (HNE), markers of lipid oxidation. Together, these data support a
      role for apoE in the modulation of oxidative injury and in the maintenance of
      synaptic integrity and are discussed with reference to alterations in AD brain.

PMID- 11327878
TI  - The first epidermal growth factor-like domain of the low-density lipoprotein
      receptor contains a noncanonical calcium binding site.
AB  - Removal of cholesterol-containing particles from the circulation is mediated by
      the low-density lipoprotein (LDL) receptor. Upon ligand binding, the receptor
      ligand complex is endocytosed, and the ligand is released. The important
      biological role of the LDL receptor (LDLR) has been highlighted by the
      identification of more than 400 LDLR mutations that are associated with familial
      hypercholesterolemia. The extracellular region of the LDLR is modular in nature
      and principally comprises multiple copies of ligand binding, epidermal growth
      factor-like (EGF), and YWTD-type domains. This report describes characterization
      of the calcium binding properties of the tandem pair of EGF domains. While only
      the C-terminal EGF module contains the consensus sequence associated with calcium
      binding, a noncanonical calcium binding site in the N-terminal domain has been
      revealed using solution NMR spectroscopy. The calcium dissociation constants for
      the N- and C-terminal sites have been measured under physiologically relevant pH
      and ionic strength conditions using a combination of solution NMR, intrinsic
      protein fluorescence, and chromophoric chelator methods to be approximately 50
      microM and approximately 10-20 microM, respectively. Identification of the novel
      calcium binding motif in LDLR sequences from other species suggests that it may
      confer specificity within the LDLR gene family. Comparison of the K(d) for the C
      terminal site with the calcium concentration in late vesicles indicates that the
      binding properties of this module may be tuned to titrate upon endocytosis of the
      LDL receptor-ligand complex, and thus calcium binding may play a role in the
      ligand dissociation process.

PMID- 11327880
TI  - Alternatively spliced form of human thyroperoxidase, TPOzanelli: activity,
      intracellular trafficking, and role in hormonogenesis.
AB  - Thyroperoxidase (TPO), a type I transmembrane heme containing glycoprotein,
      catalyzes iodide organification and thyroid hormone synthesis. One of the two
      main alternatively spliced forms of this enzyme, TPOzanelli, which is present in
      Graves's disease thyroid tissue, has a cytoplasmic domain completely modified. In
      the first stage of this study, the results of RT-PCR experiments showed that the
      TPOzanelli mRNA is present in normal thyroid tissue. We then generated CHO cell
      lines expressing the wild-type TPO (TPO1) and the alternatively spliced form
      TPOzanelli. Upon investigating a panel of 12 mAbs directed against the
      extracellular domain of TPO1 and sera from patients with a high titer of TPO
      autoantibodies, we observed that (i) the three-dimensional structure of this
      domain is similar in both isoforms; (ii) the autoantibodies recognize TPOzanelli
      as well as TPO1. The results of pulse chase and cell surface biotinylation
      experiments showed that the TPOzanelli has a shorter half-life (7 versus 11 h)
      and is expressed at the cell surface in lesser amounts than TPO1 (7 versus 15%).
      The total enzymatic activity and cell surface activity were determined in CHO
      cells expressing TPO1 and TPOzanelli, and TPO1 and TPOzanelli were found to have
      similar levels of activity. It was established that approximately 20% of the TPO
      purified from a Graves' disease thyroid gland was precipitated by polyclonal
      antibodies directed against a specific part of the cytoplasmic tail of
      TPOzanelli. This confirmed that the protein corresponding to the mRNA is present
      in the thyroid tissue. All in all, these results indicate that TPOzanelli can be
      expected to play a role in thyroid hormone synthesis and in thyroid autoimmunity.

PMID- 11327879
TI  - Protein kinase C effectors bind to multidrug ABC transporters and inhibit their
      activity.
AB  - P-Glycoprotein and homologous multidrug transporters contain a phosphorylatable
      linker sequence that was proposed to control drug efflux on the basis that it was
      indeed phosphorylated in vitro and in vivo, and that inhibitors of protein kinase
      C (PKC) inhibited both P-glycoprotein phosphorylation and activity. However, site
      directed mutagenesis of all phosphorylatable residues did not alter the drug
      resistance. The present work shows that PKC effectors are able to bind directly
      to multidrug transporters, from either cancer cells (mouse P-glycoprotein), yeast
      (Saccharomyces cerevisiae Pdr5p), or protozoan parasite (Leishmania tropica
      ltmdr1), and to inhibit their energy-dependent drug-efflux activity. The binding
      of staurosporine and derivatives such as CGP 41251 is prevented by preincubation
      with ATP, suggesting at least partial interaction at the ATP-binding site. In
      contrast, more hydrophobic compounds such as calphostin C and CGP 42700 bind
      outside the ATP-binding site and strongly interfere with drug interaction. A
      direct correlation is obtained between the efficiencies of PKC effectors to
      inhibit energy-dependent interaction of rhodamine 6G with yeast Pdr5p, to promote
      intracellular drug accumulation in various multidrug resistant cells, and to
      chemosensitize growth of resistant cells. The noncompetitive inhibition by PKC
      effectors of rhodamine 6G interaction with Pdr5p suggests that the binding might
      interfere with signal transduction between nucleotide hydrolysis and drug
      interaction. The overall results indicate that the multidrug transporters from
      different species display common features for interaction with PKC inhibitors.
      The hydrophobic derivative of staurosporine, CGP 42700, constitutes a potentially
      powerful modulator of P-glycoprotein-mediated multidrug resistance.

PMID- 11327881
TI  - A base change in the catalytic core of the hairpin ribozyme perturbs function but
      not domain docking.
AB  - The hairpin ribozyme is a small endonucleolytic RNA motif with potential for
      targeted RNA inactivation. It optimally cleaves substrates containing the
      sequence 5'-GU-3' immediately 5' of G. Previously, we have shown that tertiary
      structure docking of its two domains is an essential step in the reaction pathway
      of the hairpin ribozyme. Here we show, combining biochemical and fluorescence
      structure and function probing techniques, that any mutation of the substrate
      base U leads to a docked RNA fold, yet decreases cleavage activity. The docked
      mutant complex shares with the wild-type complex a common interdomain distance as
      measured by time-resolved fluorescence resonance energy transfer (FRET) as well
      as the same solvent-inaccessible core as detected by hydroxyl-radical protection;
      hence, the mutant complex appears nativelike. FRET experiments also indicate that
      mutant docking is kinetically more complex, yet with an equilibrium shifted
      toward the docked conformation. Using 2-aminopurine as a site-specific
      fluorescent probe in place of the wild-type U, a local structural rearrangement
      in the substrate is observed. This substrate straining accompanies global domain
      docking and involves unstacking of the base and restriction of its conformational
      dynamics, as detected by time-resolved 2-aminopurine fluorescence spectroscopy.
      These data appear to invoke a mechanism of functional interference by a single
      base mutation, in which the ribozyme-substrate complex becomes trapped in a
      nativelike fold preceding the chemical transition state.

PMID- 11327883
TI  - Dynamics of histone acetylation in Saccharomyces cerevisiae.
AB  - Rates of turnover for the posttranslational acetylation of core histones were
      measured in logarithmically growing yeast cells by radioactive acetate labeling
      to near steady-state conditions. On average, acetylation half-lives were
      approximately 15 min for histone H4, 10 min for histone H3, 4 min for histone
      H2B, and 5 min for histone H2A. These rates were much faster than the several
      hours that have previously been reported for the rate of general histone
      acetylation and deacetylation in yeast. The current estimates are in line with
      changes in histone acetylation detected directly at specific chromatin locations
      and the speed of changes in gene expression that can be observed. These results
      emphasize that histone acetylation within chromatin is subject to constant flux.
      Detailed analysis revealed that the turnover rates for acetylation of histone H3
      are the same from mono- through penta-acetylated forms. A large fraction of
      acetylated histone H3, including possibly all tetra- and penta-acetylated forms,
      appears subject to acetylation turnover. In contrast, the rate of acetylation
      turnover for mono- and di-acetylated forms of histones H4 and H2B, and the
      fraction subject to acetylation turnover, was lower than for multi-acetylated
      forms of these histones. This difference may reflect the difference in location
      of these histones within the nucleosome, a difference in the spectrum of histone
      specific acetylating and deacetylating enzymes, and a difference in the role of
      acetylation in different histones.

PMID- 11327882
TI  - HU binding to DNA: evidence for multiple complex formation and DNA bending.
AB  - HU, a nonspecific histone-like DNA binding protein, participates in a number of
      genomic events as an accessory protein and forms multiple complexes with DNA. The
      HU-DNA binding interaction was characterized by fluorescence, generated with the
      guanosine analogue 3-methyl-8-(2-deoxy-beta-D-ribofuranosyl)isoxanthopterin (3
      MI) directly incorporated into DNA duplexes. The stoichiometry and equilibrium
      binding constants of complexes formed between HU and 13 and 34 bp DNA duplexes
      were determined using fluorescence anisotropy and analytical ultracentrifugation.
      These measurements reveal that three HU molecules bind to the 34 bp duplexes,
      while two HU molecules bind to the 13 bp duplex. The data are well described by
      an independent binding site model, and the association constants for the first
      binding event for both duplexes are similar (approximately 1 x 10(6) M(-1)),
      indicating that HU binding affinity is independent of duplex length. Further
      analysis of the binding curves in terms of a nonspecific binding model is
      indicative that HU binding to DNA exhibits little to no cooperativity. The
      fluorescence intensity also increases upon HU binding, consistent with decreased
      base stacking and increased solvent exposure of the 3-MI fluorescence probe.
      These results are suggestive of a local bending or unwinding of the DNA. On the
      basis of these results we propose a model in which bending of DNA accompanies HU
      binding. Up to five complex bands are observed in gel mobility shift assays of HU
      binding to the 34 bp duplexes. We suggest that protein-induced bending of the DNA
      leads to the observation of complexes in the gel, which have the same molecular
      weight but different relative mobilities.

PMID- 11327884
TI  - Stability studies of FhuA, a two-domain outer membrane protein from Escherichia
      coli.
AB  - FhuA (MM 78.9 kDa) is an Escherichia coli outer membrane protein that transports
      iron coupled to ferrichrome and is the receptor for a number of bacteriophages
      and protein antibiotics. Its three-dimensional structure consists of a 22
      stranded beta-barrel lodged in the membrane, extracellular hydrophilic loops, and
      a globular domain (the "cork") located within the beta-barrel and occluding it.
      This unexpected structure raises questions about the connectivity of the
      different domains and their respective roles in the different functions of the
      protein. To address these questions, we have compared the properties of the wild
      type receptor to those of a mutated FhuA (FhuA Delta) missing a large part of the
      cork. Differential scanning calorimetry experiments on wild-type FhuA indicated
      that the cork and the beta-barrel behave as autonomous domains that unfold at 65
      and 75 degrees C, respectively. Ferrichrome had a strong stabilizing effect on
      the loops and cork since it shifted the first transition to 71.4 degrees C.
      Removal of the cork destabilized the protein since a unique transition at 61.6
      degrees C was observed even in the presence of ferrichrome. FhuA Delta showed an
      increased sensitivity to proteolysis and to denaturant agents and an impairment
      in phage T5 and ferrichrome binding.

PMID- 11327885
TI  - Interaction of cholesterol with sphingomyelin in mixed membranes containing
      phosphatidylcholine, studied by spin-label ESR and IR spectroscopies. A possible
      stabilization of gel-phase sphingolipid domains by cholesterol.
AB  - The ESR spectra from different positional isomers of sphingomyelin and
      phosphatidylcholine spin-labeled in their acyl chain have been studied in
      sphingomyelin(cerebroside)-phosphatidylcholine mixed membranes that contain
      cholesterol. The aim was to investigate mechanisms by which cholesterol could
      stabilize possible domain formation in sphingolipid-glycerolipid membranes. The
      outer hyperfine splittings in the ESR spectra of sphingomyelin and
      phosphatidylcholine spin-labeled on the 5 C atom of the acyl chain were
      consistent with mixing of the components, but the perturbations on adding
      cholesterol were greater in the membranes containing sphingomyelin than in those
      containing phosphatidylcholine. Infrared spectra of the amide I band of egg
      sphingomyelin were shifted and broadened in the presence of cholesterol to a
      greater extent than the carbonyl band of phosphatidylcholine, which was affected
      very little by cholesterol. Two-component ESR spectra were observed from lipids
      spin-labeled on the 14 C atom of the acyl chain in cholesterol-containing
      membranes composed of sphingolipids, with or without glycerolipids
      (sphingomyelin/cerebroside and sphingomyelin/cerebroside/phosphatidylcholine
      mixtures). These results indicate the existence of gel-phase domains in otherwise
      liquid-ordered membranes that contain cholesterol. In the gel phase of egg
      sphingomyelin, the outer hyperfine splittings of sphingomyelin spin-labeled on
      the 14-C atom of the acyl chain are smaller than those for the corresponding spin
      labeled phosphatidylcholine. In the presence of cholesterol, this situation is
      reversed; the outer splitting of 14-C spin-labeled sphingomyelin is then greater
      than that of 14-C spin-labeled phosphatidylcholine. This result provides some
      support for the suggestion that transbilayer interdigitation induced by
      cholesterol stabilizes the coexistence of gel-phase and "liquid-ordered" domains
      in membranes containing sphingolipids.

PMID- 11327886
TI  - The highly conserved COOH terminus of troponin I forms a Ca2+-modulated
      allosteric domain in the troponin complex.
AB  - The primary structure of the COOH-terminal region of troponin I (TnI) is highly
      conserved among the cardiac, slow, and fast skeletal muscle TnI isoforms and
      across species. Although no binding site for the other thin filament proteins is
      found at the COOH terminus of TnI, truncations of the last 19-23 amino acid
      residues reduce the activity of TnI in the inhibition of actomyosin ATPase and
      result in cardiac muscle malfunction. We have developed a specific monoclonal
      antibody (mAb), TnI-1, against the conserved COOH terminus of TnI. Using this
      mAb, isolation of the troponin complex by immunoaffinity chromatography from
      muscle homogenate and immunofluorescence microscopic staining of myofibrils
      indicate that the COOH terminus of TnI forms an exposed structure in the muscle
      thin filament. Binding of this mAb to the COOH terminus of cardiac TnI induced
      extensive conformational changes in the protein, suggesting an allosteric role of
      this region in the functional integrity of troponin. In the absence of Ca2+, the
      binding of troponin C and troponin T to TnI had very little effect on the
      conformation of the COOH terminus of TnI as indicated by the unaffected mAb
      affinity for the TnI-1 epitope. However, Ca2+ significantly increased the
      accessibility of the TnI-1 epitope on TnI in the presence of troponin C and
      troponin T. The results provide evidence that the COOH terminus is an essential
      structure in TnI and participates in the allosteric switch during Ca2+ activation
      of contraction.

PMID- 11327887
TI  - A novel copper A containing menaquinol NO reductase from Bacillus azotoformans.
AB  - The molecular biology and biochemistry of denitrification in gram-negative
      bacteria has been studied extensively. However, little is known about this
      process in gram-positive bacteria. We have purified the NO reductase from the
      cytoplasmic membrane of the gram-positive bacterium Bacillus azotoformans. The
      purified enzyme consists of two subunits with apparent molecular masses of 16 and
      40 kDa based on SDS-PAGE. Analytical and spectroscopic determinations revealed
      the presence of one non-heme iron, two copper atoms and of two b-type hemes per
      enzyme complex. Heme c was absent. Using EPR and UV-visible spectroscopy, it was
      determined that one of the hemes is a low-spin heme b, in which the two axial
      histidine imidazole planes are positioned at an angle of 60-70 degrees. The
      second heme b is high-spin binding CO in the reduced state. The high-spin heme
      center and the non-heme iron are EPR silent. They are proposed to form a
      binuclear center where reduction of NO occurs. There are two novel features of
      this enzyme that distinguish it from other NO reductases. First, the enzyme
      contains copper in form of copper A, an electron carrier up to now only detected
      in cytochrome oxidases and nitrous oxide reductases. Second, the enzyme uses
      menaquinol as electron donor, whereas cytochrome c, which is the substrate of
      other NO reductases, is not used. Copper A and both hemes are reducible by
      menaquinol. This new NO reductase is thus a menaquinol:NO oxidoreductase. With
      respect to its prosthetic groups the B. azotoformans NO reductase is a true
      hybrid between copper A containing cytochrome oxidases and NO reductases present
      in gram-negative bacteria. It may represent the most ancient "omnipotent"
      progenitor of the family of heme-copper oxidases.

PMID- 11327888
TI  - Potent direct inhibition of mammalian phospholipase D isoenzymes by calphostin-c.
AB  - Calphostin-c inhibits protein kinase C (PKC) isoenzymes by covalent modification
      of the lipid binding regulatory domain. Exposure of cells to calphostin-c elicits
      PKC independent effects including disruption of intracellular transport, growth
      inhibition, and stimulation of apoptosis suggesting actions at additional
      targets. Phospholipase D (PLD) enzymes are targets for activation by PKC. We have
      investigated the PKC isoenzyme selectivity for activation of two mammalian PLD
      enzymes, PLD1 and PLD2, by PKC. We examined the sensitivity of this process to
      widely used PKC inhibitors and report the surprising finding that calphostin-c is
      a potent direct inhibitor of PLD1 and PLD2. In vitro, calphostin-c inhibits
      activity of both PLD1 and PLD2 with an IC(50) of approximately 100 nM. Inhibition
      is not overcome by protein and lipid activators of these enzymes and does not
      involve blockade of phosphatidylinositol 4,5-bisphosphate-dependent PLD binding
      to substrate containing liposomes. Studies using a series of deletion and point
      mutants of the enzymes suggest that calphostin-c targets the PLD catalytic
      domain. Inhibition of PLD by calphostin-c in vitro involves stable and apparently
      irreversible modification of the enzyme. Activity of both PLD1 and PLD2 can be
      inhibited by calphostin-c treatment of intact cells in a manner that is
      independent of upstream actions of PKC. Our results suggest that inhibition of
      PLD1 and PLD2 may explain some of the PKC-independent effects of calphostin-c
      observed when the compound is applied to intact cells.

PMID- 11327889
TI  - Unusual noninterpenetrating (3,6) topological network assembled by semirigid
      benzimidazole-based bridging ligand.

PMID- 11327890
TI  - Modeling the active site chemistry of liver alcohol dehydrogenase: mononuclear
      zinc methanol and N,N-dimethylformamide complexes of a nitrogen/sulfur ligand
      possessing an internal hydrogen bond donor.

PMID- 11327891
TI  - [Co(en)3][B(2)P(3)O(11)(OH)(2)]: a novel borophosphate templated by a transition
      metal complex.

PMID- 11327893
TI  - Simple simultaneous encapsulation of both single H atoms and single D atoms in
      octasilsesquioxane, double four-ring cages using a deuterated organic solvent.

PMID- 11327892
TI  - Imposition of chirality in a dinuclear triple-stranded helicate by ion pair
      formation.

PMID- 11327894
TI  - A mechanistic study of the reaction between a diiron(II) complex [FeII(2)(mu
      OH)2(6-Me3-TPA)2](2+) and O2 to form a diiron(III) peroxo complex.
AB  - A kinetic study of the reaction between a diiron(II) complex [Fe(II)(2)(mu
      OH)(2)(6-Me(3)-TPA)(2)](2+) 1, where 6-Me(3)-TPA = tris(6-methyl-2
      pyridylmethyl)amine, and dioxygen is presented. A diiron(III) peroxo complex
      [Fe(III)(2)(mu-O)(mu-O(2))(6-Me(3)-TPA)(2)](2+) 2 forms quantitatively in
      dichloromethane at temperatures from -80 to -40 degrees C. The reaction is first
      order in [Fe(II)(2)] and [O(2)], with the activation parameters DeltaH(double
      dagger) = 17 +/- 2 kJ mol(-1) and DeltaS(double dagger) = -175 +/- 20 J mol(-1)
      K(-1). The reaction rate is not significantly influenced by the addition of H(2)O
      or D(2)O. The reaction proceeds faster in more polar solvents (acetone and
      acetonitrile), but the yield of 2 is not quantitative in these solvents. Complex
      1 reacts with NO at a rate about 10(3) faster than with O(2). The mechanistic
      analysis suggests an associative rate-limiting step for the oxygenation of 1,
      similar to that for stearoyl-ACP Delta(9)-desaturase, but distinct from the
      probable dissociative pathway of methane monoxygenase. An eta(1)-superoxo
      Fe(II)Fe(III) species is a likely steady-state intermediate during the
      oxygenation of complex 1.

PMID- 11327895
TI  - Quadridentate bridging EO(4)(2-) (E = S, Mo, W) ligands and their role as
      electronic bridges.
AB  - Three compounds containing two quadruply bonded Mo(2)(DAniF)(3) (DAniF = N,N'-di
      p-anisylformamidinate) units linked by tetrahedral EO(4)(2-) anions (E = S, Mo,
      W) have been prepared and characterized by crystallography and NMR. The linkers
      in these [Mo(2)(DAniF)(3)](2)(mu-EO(4)) compounds hold the Mo(2) units in an
      approximately perpendicular orientation and mediate strong electrochemical
      communication between them. Each of the three compounds shows two quasireversible
      (mu-SO(4)) or fully reversible (mu-MoO(4), mu-WO(4)) features in its cyclic
      voltammogram corresponding to successive oxidation of each of its Mo(2) units.
      The DeltaE(1/2) values are the largest thus far measured for Mo(2)-X-Mo(2)
      bridged complexes and may be sufficiently large to permit isolation of the singly
      oxidized species.

PMID- 11327896
TI  - Redox-associated eta(1) to eta(2) conversion of disulfide ligands in dinuclear
      ruthenium complexes.
AB  - Disulfide-bridged dinuclear ruthenium complexes [[Ru(MeCN)(P(OMe)(3))(2)](2)(mu
      X)(mu,eta(2)-S(2))][ZnX(3)(MeCN)] (X = Cl (2), Br (4)),
      [[Ru(MeCN)(P(OMe)(3))(2)](2)(mu-Cl)(2)(mu,eta(1)-S(2))](CF(3)SO(3)) (5),
      [[Ru(MeCN)(P(OMe)(3))(2)](2)(mu-Cl)(mu,eta(2)-S(2))](BF(4)) (6), and
      [[Ru(MeCN)(2)(P(OMe)(3))(2)](2)(mu-Cl)(mu,eta(1)-S(2))](CF(3)SO(3))(3) (7) were
      synthesized, and the crystal structures of 2 and 4 were determined. Crystal data:
      2, triclinic, P1, a = 15.921(4) A, b = 17.484(4) A, c = 8.774(2) A, alpha =
      103.14(2) degrees, beta = 102.30(2) degrees, gamma = 109.68(2) degrees, V =
      2124(1) A(3), Z = 2, R (R(w)) = 0.055 (0.074); 4, triclinic, P1 a = 15.943(4) A,
      b = 17.703(4) A, c = 8.883(1) A, alpha = 102.96(2) degrees, beta = 102.02(2)
      degrees, gamma = 109.10(2) degrees, V = 2198.4(9) A(3), Z = 2, R (R(w)) = 0.048
      (0.067). Complexes 2 and 4 were obtained by reduction of the disulfide-bridged
      ruthenium complexes [[RuX(P(OMe)(3))(2)](2)(mu-X)(2)(mu,eta(1)-S(2))] (X = Cl
      (1), Br (3)) with zinc, respectively. Complex 5 was synthesized by oxidation of 2
      with AgCF(3)SO(3). Through these redox steps, the coordination mode of the
      disulfide ligand was converted from mu,eta(1) in 1 and 3 to mu,eta(2) in 2 and 4
      and further reverted to mu,eta(1) in 5. Electrochemical studies of 6 indicated
      that similar conversion of the coordination mode occurs also in electrochemical
      redox reactions.

PMID- 11327897
TI  - Rapid solid-state synthesis of tantalum, chromium, and molybdenum nitrides.
AB  - Solid-state metathesis (exchange) reactions can be used to synthesize many
      different transition-metal nitrides under ambient conditions including TiN, ZrN,
      and NbN. Typical metathesis reactions reach temperatures of greater than 1300
      degrees C in a fraction of a second to produce these refractory materials in
      highly crystalline form. Likely due to the large amount of heat produced in these
      solid-state reactions, some transition-metal nitrides such as TaN, CrN, and gamma
      Mo(2)N cannot easily be synthesized under ambient conditions. Here metathesis
      reactions are demonstrated to produce the cubic nitrides TaN, CrN, and gamma
      Mo(2)N when sufficient pressure is applied before the reaction is initiated. By
      pressing a pellet of TaCl(5) and Li(3)N with an embedded iron wire, crystalline
      cubic TaN forms under 45 kbar of pressure after a small current is used to
      initiate the chemical reaction. Crystalline cubic CrN is synthesized from CrCl(3)
      and Li(3)N initiated under 49 kbar of pressure. Crystalline gamma-Mo(2)N is
      produced from MoCl(5) and Ca(3)N(2) (since MoCl(5) and Li(3)N self-detonate)
      initiated under 57 kbar of pressure. The addition of ammonium chloride to these
      metathesis reactions drastically lowers the pressure requirements for the
      synthesis of these cubic nitrides. For example, when 3 mol of NH(4)Cl is added to
      CrCl(3) and Li(3)N, crystalline CrN forms when the reaction is initiated with a
      resistively heated wire under ambient conditions. Cubic gamma-Mo(2)N also forms
      at ambient pressure when 3 mol of NH(4)Cl is added to the reactants MoCl(5) and
      Ca(3)N(2) and ignited with a resistively heated wire. A potential advantage of
      synthesizing gamma-Mo(2)N under ambient conditions is the possibility of forming
      high-surface-area materials, which could prove useful for catalysis. Nitrogen
      adsorption (BET) indicates a surface area of up to 30 m(2)/g using a Langmuir
      model for gamma-Mo(2)N produced by a metathesis reaction at ambient pressure. The
      enhanced surface area is confirmed using scanning electron microscopy.

PMID- 11327898
TI  - Trigonal planar copper(I) complex: synthesis, structure, and spectra of a redox
      pair of novel copper(II/I) complexes of tridentate bis(benzimidazol-2'-yl) ligand
      framework as models for electron-transfer copper proteins.
AB  - The copper(II) and copper(I) complexes of the chelating ligands 2,6
      bis(benzimidazol-2'-ylthiomethyl)pyridine (bbtmp) and N,N-bis(benzimidazol-2'
      ylthioethyl)methylamine (bbtma) have been isolated and characterized by
      electronic and EPR spectra. The molecular structures of a redox pair of Cu(II/I)
      complexes, viz., [Cu(bbtmp)(NO(3))]NO(3), 1, and [Cu(bbtmp)]NO(3), 2, and of
      [Cu(bbtmp)Cl], 3, have been determined by single-crystal X-ray crystallography.
      The cation of the green complex [Cu(bbtmp)(NO(3))]NO(3) possesses an almost
      perfectly square planar coordination geometry in which the corners are occupied
      by the pyridine and two benzimidazole nitrogen atoms of the bbtmp ligand and an
      oxygen atom of the nitrate ion. The light-yellow complex [Cu(bbtmp)]NO(3)
      contains copper(I) with trigonal planar coordination geometry constituted by the
      pyridine and two benzimidazole nitrogen atoms of the bbtmp ligand. In the yellow
      chloride complex [Cu(bbtmp)Cl] the asymmetric unit consists of two complex
      molecules that are crystallographically independent. The coordination geometry of
      copper(I) in these molecules, in contrast to the nitrate, is tetrahedral, with
      pyridine and two benzimidazole nitrogen atoms of bbtmp ligand and the chloride
      ion occupying the apexes. The above coordination structures are unusual in that
      the thioether sulfurs are not engaged in coordination and the presence of two
      seven-membered chelate rings facilitates strong coordination of the benzimidazole
      nitrogens and discourage any distortion in Cu(II) coordination geometry. The
      solid-state coordination geometries are retained even in solution, as revealed by
      electronic, EPR, and (1)H NMR spectra. The electrochemical behavior of the
      present and other similar CuN(3) complexes has been examined, and the
      thermodynamic aspects of the electrode process are correlated to the
      stereochemical reorganizations accompanying the redox changes. The influence of
      coordinated pyridine and amine nitrogen atoms on the spectral and electrochemical
      properties has been discussed.

PMID- 11327899
TI  - The stable diiron(2.5) complex ion [(NC)(5)Fe(mu-tz)Fe(CN)5](5-), tz = 1,2,4,5
      tetrazine, and its neighboring oxidation states.
AB  - The conceptually simple mixed-valent diiron compound (NEt(4))(5)[(NC)(5)Fe(mu
      tz)Fe(CN)(5)] with the 1,2,4,5-tetrazine (tz) bridging ligand was obtained as a
      thermally and air-stable material that displays large and highly variable
      electrochemical comproportionation constants between about 10(8) (in water) and
      10(19.0) (in acetonitrile). Strong metal-metal interaction is also evident from
      spectroscopic results obtained for the solid and for the dissolved species. The
      rather intense intervalence charge-transfer band occurs around 2400 nm; infrared
      and Mossbauer spectra reveal the high spectroscopic symmetry of the system
      according to an (Fe(2.5))(2) formulation. DFT calculations on the [(NC)(5)Fe(mu
      tz)Fe(CN)(5)](6-) ion confirm the presence of very low-lying pi(tz) and high
      lying d(Fe) orbitals.

PMID- 11327900
TI  - Dicopper(I) complexes with reduced states of 3,6-bis(2'-pyrimidyl)-1,2,4,5
      tetrazine: crystal structures and spectroscopic properties of the free ligand, a
      radical species, and a complex of the 1,4-dihydro form.
AB  - The complexes [(mu-bmtz(*-))[Cu(PPh(3))(2)](2)](BF(4)) (1) and [(mu
      H(2)bmtz)[Cu(PPh(3))(2)](2)](BF(4))(2) (2) (bmtz = 3,6-bis(2'-pyrimidyl)-1,2,4,5
      tetrazine and H(2)bmtz = 1,4-dihydro-3,6-bis(2'-pyrimidyl)-1,2,4,5-tetrazine)
      were obtained as stable materials that could be crystallized for structure
      determination. 1.2 CH(2)Cl(2): C(84)H(70)BCl(4)Cu(2)F(4)N(8)P(4); monoclinic,
      C2/c; a = 26.215(7) A, b = 22.122(6) A, c = 18.114(5) A, beta = 133.51(1)
      degrees; Z = 4. 2.CH(2)Cl(2): C(83)H(70)B(2)Cl(2)Cu(2)F(8)N(8)P(4); triclinic,
      P1; a = 10.948(2) A, b = 12.067(2) A, c = 30.287(6) A, alpha = 93.82(3) degrees,
      beta = 94.46(3) degrees, gamma = 101.60(3) degrees; Z = 2. Bmtz itself was also
      structurally characterized (C(10)H(6)N(8); monoclinic, P2(1)/c; a = 3.8234(8) A,
      b = 10.147(2) A, c = 13.195(3) A, beta = 94.92(3) degrees; Z = 2). Whereas the
      radical complex ion contains a planar tetrazine ring in the center, the 1,4
      dihydrotetrazine heterocycle in the corresponding complex of H(2)bmtz is
      considerably folded. Both systems exhibit slight twists between the tetrazine and
      the pyrimidine rings. The intra-tetrazine distances are characteristically
      affected by the electron transfer, as is also evident from a comparison with the
      new structure of free bmtz; the bonding to copper(I) changes accordingly.
      Spectroscopy including X- and W-band EPR of the radical species confirms that the
      electron addition is mainly to the tetrazine ring.

PMID- 11327901
TI  - The quest for beryllium peroxides.
AB  - There is no experimental proof documented in the literature for the existence of
      any beryllium peroxide compound. All recent pertinent preparative attempts
      described in this work, using a range of beryllium salts with various peroxides
      as reagents under mild conditions, were equally unsuccessful. (1)H and (9)Be NMR
      investigations of aqueous solutions containing beryllium salts and hydrogen
      peroxide in a broad pH range also gave no definite evidence for the presence of
      peroxoberyllates as components of the manifold equilibria in such solutions.
      Quantum chemical calculations have therefore been carried out to delineate the
      energetics and structures of various beryllium peroxide model compounds. Standard
      Hartree-Fock and density functional methods were employed at various levels of
      sophistication. The series of prototypes considered consists of [BeOH](+),
      Be(OH)(2), Be(OH)(OOH), Be(OOH)(2), [Be(O(2))(2)](2-), [BeO(2)(OH(2))(2)], and
      [Be(2)(O(2))(2)(OH(2))(4)] (all in the gas phase). Surprisingly, the triatomic
      cation [BeOH](+) has been found to have a linear structure. All the Be
      O(peroxide) bonds are found to be rather long, suggesting weaker bonding compared
      to the Be-O bonds in aquo, hydroxo, or oxo complexes. Hydrogen peroxide or anions
      derived therefrom are therefore not able to compete successfully with water
      (hydroxide anions) in aqueous solution. In the mononuclear beryllium peroxide
      molecules, the peroxide groups form chelating units at tetrahedrally 4-coordinate
      metal atoms. The binuclear compound [Be(2)(O(2))(2)(OH(2))(4)] has a puckered six
      membered-ring structure, close to the standard chair conformation. A significant
      lengthening of the O-O bonds upon coordination to the Be(2+) centers has been
      calculated, but it is unlikely that the polarization of the peroxide group by the
      high positive charge density at Be(2+) is significant to cause an intrinsic
      instability of beryllium peroxides. All structures represent distinct local
      minima on the potential energy surface and are predicted to be (meta)stable
      species in nonaqueous media. The field of aluminum peroxides is a similar gray
      area on the map of metal and metalloid peroxides and is reminiscent of the well
      established "diagonal-relation" of Be and Al in the periodic table of the
      elements.

PMID- 11327902
TI  - Synthesis, electrochemistry, and spectroscopic characterization of bis-dirhodium
      complexes linked by axial ligands.
AB  - The synthesis and electrochemical and spectroscopic properties of bis-dirhodium
      complexes containing ap or dpf bridging ligands, (ap)(4)Rh(2)(C triple bond
      C)(2)Rh(2)(ap)(4) (2) and (dpf)(4)Rh(2)(CNC(6)H(4)NC)Rh(2)(dpf)(4) (4), were
      investigated (where ap and dpf are the 2-anilinopyridinate and N,N'
      diphenylformamidinate ions, respectively). The related "simple" dirhodium
      species, (ap)(4)Rh(2)(C triple bond C)(2)Si(CH(3))(3) (1) and
      (dpf)(4)Rh(2)(CNC(6)H(5)) (3), with the same set of bridging ligands were also
      synthesized and their properties compared to those of the analogous bis-dirhodium
      complexes. Compound 1 was obtained by mixing (ap)(4)Rh(2)Cl and Li(C triple bond
      C)(2)Si(CH(3))(3) in refluxing THF for 16 h under vacuum while compound 2 was
      prepared by a reaction between (ap)(4)Rh(2)(C triple bond C)(2)Li and
      (ap)(4)Rh(2)Cl under similar conditions. The reaction between (CF(3)COO)(4)Rh(2)
      and molten Hdpf under vacuum for 24 h leads to the generation of compound 3 with
      a yield of 65%. The red-orange compound 4 was obtained upon addition of 0.5 equiv
      of CNC(6)H(4)NC at room temperature to a CH(2)Cl(2) solution containing
      (dpf)(4)Rh(2) which was synthesized according to a method described previously in
      the literature. Compound 1 crystallizes in the triclinic space group P1, with a =
      10.164(3) A, b = 13.881(3) A, c = 18.805(4) A, alpha = 73.55(2) degrees, beta =
      77.89(2) degrees, gamma = 84.85(2) degrees, and Z = 2. Crystals of 2 were not
      good enough to collect adequate data for X-ray analysis, but the identity of this
      compound was confirmed, along with its P1; space group. Crystals of 3 and 4
      belong to the monoclinic, P2(1)/c space group and the triclinic, P1; space group,
      respectively, with a = 13.5254(5) A, b = 13.7387(4) A, c = 27.2011(12) A, beta =
      102.637(2) degrees, and Z = 4 for 3 and a = 13.866(8) A, b = 14.756(7) A, c =
      15.008(6) A, alpha = 79.91(3) degrees, beta = 87.72(4) degrees, gamma = 89.19(4)
      degrees, and Z = 1 for 4. Compound 1 exhibits a single reversible oxidation at
      E(1/2) = 0.66 V and a single reversible reduction at E(1/2) = -0.44 V vs SCE in
      THF, 0.2 M TBAP. Both processes involve a one-electron transfer. Compound 2
      undergoes a reversible oxidation at E(1/2) = 0.60 V and two separate one-electron
      transfer reductions at E(1/2) = -0.52 and -0.65 V in THF, 0.2 M TBAP. The
      oxidation involves two overlapped one-electron-transfer processes. Compounds 3
      and 4 undergo two reversible oxidations in CH(2)Cl(2), 0.1 M TBAP located at
      E(1/2) = 0.23 and 1.22 V (3) or 0.22 and 1.20 V (4). Each redox reaction of 3
      involves a one-electron-transfer step while each redox reaction of 4 involves two
      overlapping one-electron transfers. Compound 2 shows interaction between the two
      dirhodium cores upon reduction, while 4 gives no evidence of electronic
      interaction between the two dirhodium units during either reduction or oxidation.
      An ESR signal with axial symmetry was obtained for the neutral compounds 1 and 2,
      and a similar spectrum was obtained for the singly oxidized products of compounds
      3 and 4, thus suggesting the electronic configuration of
      (sigma)(2)(pi)(4)(delta)(2)(pi)(4)(delta)(1) for the neutral compounds 1 and 2 as
      well as for the oxidized compounds 3 and 4. The four compounds were also
      characterized by FTIR and UV-visible spectroscopy as well as by mass
      spectrometry.

PMID- 11327903
TI  - Syntheses, structural determination, and electrochemistry of Ru(2)(Fap)(4)Cl and
      Ru(2)(Fap)(4)(NO)Cl.
AB  - Ru(2)(Fap)(4)Cl and Ru(2)(Fap)(4)(NO)Cl, where Fap is the 2-(2
      fluoroanilino)pyridinate anion, were synthesized, and their structural,
      electrochemical, and spectroscopic properties were characterized.
      Ru(2)(Fap)(4)Cl, which was obtained by reaction between Ru(2)(O(2)CCH(3))(4)Cl
      and molten HFap, crystallizes in the monoclinic space group P2(1)/c, with a =
      11.2365(4) A, b = 19.9298(8) A, c = 19.0368(7) A, beta = 90.905(1) degrees, and Z
      = 4. The presence of three unpaired electrons on the Ru(2)(5+) core and the
      2.2862(3) A Ru-Ru bond length for Ru(2)(Fap)(4)Cl are consistent with the
      electronic configuration (sigma)(2)(pi)(4)(delta)(2)(pi*)(2)(delta*)(1). The
      reaction between Ru(2)(Fap)(4)Cl and NO gas yields Ru(2)(Fap)(4)(NO)Cl, which
      crystallizes in the orthorhombic space group Pbca, with a = 10.0468(6) A, b =
      18.8091(10) A, c = 41.7615(23) A, and Z = 8. The Ru-Ru bond length of
      Ru(2)(Fap)(4)(NO)Cl is 2.4203(8) A, while its N-O bond length and Ru-N-O bond
      angle are 1.164(8) A and 155.8(6) degrees, respectively. Ru(2)(Fap)(4)(NO)Cl can
      be formulated as a formal Ru(2)(II,II)(NO(+)) complex with a linear Ru-N-O group,
      and the proposed electronic configuration for this compound is
      (sigma)(2)(pi)(4)(delta)(2)(pi*)(3)(delta*)(1). The binding of NO to
      Ru(2)(Fap)(4)Cl leads to some structural changes of the Ru(2)(Fap)(4) framework
      and a stabilization of the lower oxidation states of the diruthenium unit. Also,
      IR spectroelectrochemical studies of Ru(2)(Fap)(4)(NO)Cl show that NO remains
      bound to the complex upon reduction and that the first reduction involves the
      addition of an electron on the diruthenium core and not on the NO axial ligand.

PMID- 11327904
TI  - Syntheses and reactions of the fluorinated cyclic thionylphosphazene
      NSO(Ar)[NPF(2)]2(Ar = 4-t-BuC(6)H(4)-) with difunctional reagents.
AB  - The S-aryl substituted thionylphosphazene (Cl(2)PN)(2)[4-t-BuC(6)H(4)(O)SN] (1)
      was prepared by Friedel-Craft's reaction of NSOCl(NPCl(2))(2) with tert
      butylbenzene. When it reacted with excess KSO(2)F at 110 degrees C, the P-Cl
      bonds of 1 were fluorinated, yielding the tetrafluorothionylphosphazene,
      (F(2)PN)(2)[4-t-BuC(6)H(4)(O)SN] (2). An equimolar reaction of 2 with dilithiated
      1,3-propanediol in THF at -78 degrees C resulted in the formation of the ansa
      substituted compound CH(2)(CH(2)O)(2)[FPN](2)[4-t-BuC(6)H(4)(O)SN] (3). The
      crystal structures of 2 and 3 were determined. In 3 the ansa ring is trans on the
      PNS heterocycle with respect to the aryl group. Reaction of 2 with the disiloxane
      (CF(2)CH(2)OSiMe(3))(2), in the presence of catalytic amounts of CsF in THF at 90
      degrees C, resulted in the formation of the dispiro compound
      [(CF(2)CH(2)O)(2)PN](2)[4-t-BuC(6)H(4)(O)SN] (4). Compounds 1-4 were
      characterized by IR, NMR ((1)H, (13)C, (19)F, (31)P), mass spectral, and
      elemental analyses.

PMID- 11327905
TI  - MTi(0.7)Mo(0.3)Mo(5)O(10) (M = SR, Eu), first evidence of mono- and bicapped
      bioctahedral Mo(11) and Mo(12) clusters: synthesis, crystal structures, and
      physical properties.
AB  - The novel quaternary reduced molybdenum oxides MTi(0.7)Mo(0.3)Mo(5)O(10) (M = Sr,
      Eu) have been synthesized by solid-state reaction at 1400 degrees C for 48 h in
      sealed molybdenum crucibles. Their crystal structures were determined on single
      crystals by X-ray diffraction. Both compounds crystallize in the orthorhombic
      space group Pbca with 8 formula units per cell and the following lattice
      parameters: a(Sr) = 9.1085 (7), b(Sr) = 11.418 (1), and c(Sr) = 15.092 (3) A;
      a(Eu) = 9.1069 (7), b(Eu) = 11.421 (2), and c(Eu) = 15.075 (1) A. The Mo network
      is dominated by bioctahedral Mo(10) clusters, which coexist randomly with Mo(11)
      and Mo(12) clusters (monocapped and bicapped Mo(10) clusters). The Mo-Mo
      distances within the clusters range from 2.62 to 2.92 A and the Mo-O distances
      from 1.99 to 2.17 A as usually observed in the reduced molybdenum oxides. The
      Sr(2+) and Eu(2+) ions occupy large cavities, which result from the fusion of two
      cubooctahedra and thus are surrounded by 11 oxygen atoms. The M-O distances range
      from 2.50 to 3.23 A for the Sr compound and from 2.49 to 3.24 A for the Eu
      analogue. Single-crystal resistivity measurements indicate that both materials
      are poor metals with transitions to semiconducting states below 50 and 40 K and
      room temperature resistivity values of 9 x 10(-3) and 5 x 10(-3) Omega.cm for the
      Sr and Eu compounds, respectively. The magnetic susceptibility data indicate
      paramagnetic behavior due to the Eu(2+) moment at high temperatures for the Eu
      compound and do not reveal the existence of localized moments on the Mo and Ti
      sublattice in the Sr compound. An XPS study clearly suggests that the isolated Ti
      ions are tetravalent. Theoretical considerations preclude the existence of
      heterometallic Mo-Ti clusters.

PMID- 11327906
TI  - Ionic liquids based on FeCl(3) and FeCl(2). Raman scattering and ab initio
      calculations.
AB  - We have prepared ionic liquids by mixing either iron(II) chloride or iron(III)
      chloride with 1-butyl-3-methylimidazolium chloride (BMIC). Iron(II) chloride
      forms ionic liquids from a mole ratio of 1 FeCl(2)/3 BMIC to almost 1 FeCl(2)/1
      BMIC. Both Raman scattering and ab initio calculations indicate that FeCl(4)(2-)
      is the predominant iron-containing species in these liquids. Iron(III) chloride
      forms ionic liquids from a mole ratio of 1 FeCl(3)/1.9 BMIC to 1.7 FeCl(3)/1
      BMIC. When BMIC is in excess, Raman scattering indicates the presence of FeCl(4
      ). When FeCl(3) is in excess, Fe(2)Cl(7-) begins to appear and the amount of
      Fe(2)Cl(7-) increases with increasing amounts of FeCl(3). Ionic liquids were also
      prepared from a mixture of FeCl(2) and FeCl(3) and are discussed. Finally, we
      have used both Hartree-Fock and density functional theory methods to compute the
      optimized structures and vibrational spectra for these species. An analysis of
      the results using an all-electron basis set, 6-31G, as well as two different
      effective core potential basis sets, LANL2DZ and CEP-31G is presented.

PMID- 11327907
TI  - A sterically hindered N,N,O tripod ligand and its zinc complex chemistry.
AB  - The new ligand bis(2-picolyl)(2-hydroxy-3,5-di-tert-butylbenzyl)amine (HL) was
      prepared from bis(2-picolyl)amine and 2,4-di-tert-butyl-6-(chloromethyl)phenol.
      It acts as a tetradentate N,N,O tripod ligand ensuring 5-fold coordination in all
      its zinc complexes L.Zn-X. The central complex of the series was
      [L.Zn(OH(2))]ClO(4) (1) obtained from zinc perchlorate. Together with the more
      labile complex L.Zn-C(2)H(5) (2), obtained from diethyl zinc, it was used as a
      starting material for ligand substitutions. In the presence of bases, 1 was
      converted to L.Zn-OH (3), [L.Zn(py)]ClO(4) (4), and [(L.Zn)(3)(mu(3)
      CO(3))]ClO(4) (5). Metathetical reactions produced the neutral complexes L.Zn-X
      with X = Br (6), OAc (7), OC(6)H(5) (8), SC(6)H(5) (9), OP(O)(OPh)(2) (10), p
      nitrophenolate (11), 1-methyluracilate (12), o-formylphenolate (13), and o
      hydroxymethylphenolate (14). Structure determinations of 1, 5, 7, 10, 11, 13, and
      14 confirmed the strictly monodentate attachment of all units X in L.Zn-X. The
      hydrolytic cleavage of tris(p-nitrophenyl) phosphate by 1 was investigated
      preparatively and kinetically. L.Zn-OH was found to be the hydrolytically active
      nucleophile. The second-order rate constant for the cleavage reaction was found
      to be slightly lower than the values for related systems, reflecting the steric
      hindrance in the tert-butyl-substituted ligand L.

PMID- 11327908
TI  - Copper(I) complexes, copper(I)/O(2) reactivity, and copper(II) complex adducts,
      with a series of tetradentate tripyridylalkylamine tripodal ligands.
AB  - Copper(I) and copper(II) complexes possessing a series of related ligands with
      pyridyl-containing donors have been investigated. The ligands are tris(2
      pyridylmethyl)amine (tmpa), bis[(2-pyridyl)methyl]-2-(2-pyridyl)ethylamine
      (pmea), bis[2-(2-pyridyl)ethyl]-(2-pyridyl)methylamine (pmap), and tris[2-(2
      pyridyl)ethyl]amine (tepa). The crystal structures of the protonated ligand
      H(tepa)ClO(4), the copper(I) complexes [Cu(pmea)]PF(6) (1b-PF(6)),
      [Cu(pmap)]PF(6) (1c-PF(6)), and copper(II) complexes [Cu(pmea)Cl]ClO(4).H(2)O (2b
      ClO(4).H(2)O), [Cu(pmap)Cl]ClO(4).H(2)O (2c-ClO(4).H(2)O), [Cu(pmap)Cl]ClO(4) (2c
      ClO(4)), and [Cu(pmea)F](2)(PF(6))(2) (3b-PF(6)) were determined. Crystal data:
      H(tepa)ClO(4), formula C(21)H(25)ClN(4)O(4), triclinic space group P1, Z = 2, a =
      10.386(2) A, b = 10.723(2) A, c = 11.663(2) A, alpha = 108.77(3) degrees, beta =
      113.81(3) degrees, gamma = 90.39(3) degrees; 1b-PF(6), formula
      C(19)H(20)CuF(6)N(4)P, orthorhombic space group Pbca, Z = 8, a = 14.413(3) A, b =
      16.043(3) A, c = 18.288(4) A, alpha = beta = gamma = 90 degrees; (1c-PF(6)),
      formula C(20)H(22)CuF(6)N(4)P, orthorhombic space group Pbca, Z = 8, a =
      13.306(3) A, b = 16.936(3) A, c = 19.163(4) A, alpha = beta = gamma = 90 degrees;
      2b-ClO(4).H(2)O, formula C(19)H(22)Cl(2)CuN(4)O(5), triclinic space group P1, Z =
      4, a = 11.967(2) A, b = 12.445(3) A, c = 15.668(3) A, alpha = 84.65(3) degrees,
      beta = 68.57(3) degrees, gamma = 87.33(3) degrees; 2c-ClO(4).H(2)O, formula
      C(20)H(24)Cl(2)CuN(4)O(5), monoclinic space group P2(1)/c, Z = 4, a = 11.2927(5)
      A, b = 13.2389(4) A, c = 15.0939(8) A, alpha = gamma = 90 degrees, beta =
      97.397(2) degrees; 2c-ClO(4), formula C(20)H(22)Cl(2)CuN(4)O(4), monoclinic space
      group P2(1)/c, Z = 4, a = 8.7682(4) A, b = 18.4968(10) A, c = 13.2575(8) A, alpha
      = gamma = 90 degrees, beta = 94.219(4) degrees; 3b-PF(6), formula
      [C(19)H(20)CuF(7)N(4)P](2), monoclinic space group P2(1)/n, Z = 2, a = 11.620(5)
      A, b = 12.752(5) A, c = 15.424(6) A, alpha = gamma = 90 degrees, beta = 109.56(3)
      degrees. The oxidation of the copper(I) complexes with dioxygen was studied.
      [Cu(tmpa)(CH(3)CN)](+) (1a) reacts with dioxygen to form a dinuclear peroxo
      complex that is stable at low temperatures. In contrast, only a very labile
      peroxo complex was observed spectroscopically when 1b was reacted with dioxygen
      at low temperatures using stopped-flow kinetic techniques. No dioxygen adduct was
      detected spectroscopically during the oxidation of 1c, and 1d was found to be
      unreactive toward dioxygen. Reaction of dioxygen with 1a-PF(6), 1b-PF(6), and 1c
      PF(6) at ambient temperatures leads to fluoride-bridged dinuclear copper(II)
      complexes as products. All copper(II) complexes were characterized by UV-vis,
      EPR, and electrochemical measurements. The results manifest the dramatic effects
      of ligand variations and particularly chelate ring size on structure and
      reactivity.

PMID- 11327909
TI  - Cobalt(II), nickel(II), copper(II), and zinc(II) complexes with [3(5)]adamanzane,
      1,5,9,13-tetraazabicyclo[7.7.3]nonadecane, and [(2.3)(2).2(1)] adamanzane,
      1,5,9,12-tetraazabicyclo[7.5.2]hexadecane.
AB  - Isolation of the free bicyclic tetraamine, [3(5)]adamanzane.H(2)O (1,5,9,13
      tetraazabicyclo[7.7.3]nonadecane.H(2)O), is reported along with the synthesis and
      characterization of a copper(II) complex of the smaller macrocycle
      [(2.3)(2).2(1)]adamanzane (1,5,9,12-tetraazabicyclo[7.5.2]hexadecane) and of
      three cobalt(II), four nickel(II), one copper(II), and two zinc(II) complexes
      with [3(5)]adamanzane. For nine of these compounds (2-8, 10b, and 12) the single
      crystal X-ray structures were determined. The coordination geometry around the
      metal ion is square pyramidal in [Cu([(2.3)(2).2(1)]adz)Br]ClO(4) (2) and
      trigonal bipyramidal in the isostructural structures [Cu([3(5)]adz)Br]Br (3),
      [Ni([3(5)]adz)Cl]Cl (5), [Ni([3(5)]adz)Br]Br (6), and [Co([3(5)]adz)Cl]Cl (8). In
      [Ni([3(5)]adz)(NO(3))]NO(3) (4) and [Ni([3(5)]adz)(ClO(4))]ClO(4) (7) the
      coordination geometry around nickel(II) is a distorted octahedron with the
      inorganic ligands at cis positions. The coordination polyhedron around the metal
      ion in [Co([3(5)]adz)][ZnCl(4)] (10b) and [Zn([3(5)]adz)][ZnCl(4)] (12) is a
      slightly distorted tetrahedron. Anation equilibrium constants were determined
      spectrophotometrically for complexes 2-6 at 25 and 40 degrees C and fall in the
      region 2-10 M(-1) for the halide complexes and 30-65 M(-1) for the nickel(II)
      nitrate complex (4). Rate constants for the dissociation of the macrocyclic
      ligand from the metal ions in 5 M HCl were determined for complexes 2, 3, 5, 8,
      10, and 12. The reaction rates vary from half-lives at 40 degrees C of 14 min for
      the dissociation of the Zn([3(5)]adz)(2+) complex (12) to 14-15 months for the
      Ni([3(5)]adz)Cl(+) ion (5).

PMID- 11327910
TI  - Template synthesis of a tetraazamacrocyclic ligand with two pendant pyridinyl
      groups: properties of the isomers of the metal-free ligand and of their first-row
      transition metal compounds.
AB  - The one-step reaction of [Cu(en)(2)](2+) (en = 1,2-diaminoethane) with
      formaldehyde, ethyl 2-pyridyl acetate, and base produces a mixture of [Cu(s
      pypymac)](2+) and [Cu(a-pypymac)](2+) (s-pypymac = syn-6,13-bis(2-pyridinyl)
      1,4,8,11-tetraazacyclotetradecane, a-pypymac = anti-6,13-bis(2-pyridinyl)
      1,4,8,11-tetraazacyclotetradecane; syn-to-anti ratio approximately 1:9) in low
      yield (6%). Ion exchange chromatography is used for isomer separation, and the
      two isomers of the metal-free ligand are obtained by reduction of the copper(II)
      complexes and subsequent ion exchange chromatography. Crystal structure analyses
      of the metal-free a-pypymac ligand, of two isomeric copper(II) compounds of a
      pypymac and one of s-pypymac, and of the cobalt(III) complexes of a- and s
      pypymac and nickel(II), as well as zinc(II) complexes of a-pypymac, are reported
      and discussed on the basis of the expectations from force field calculations and
      from published experimental data of the transition metal compounds of the bis
      pendant amine derivative diammac.

PMID- 11327911
TI  - Syntheses and structures of the infinite chain compounds Cs(4)Ti(3)Se(13),
      Rb(4)Ti(3)S(14), Cs(4)Ti(3)S(14), Rb(4)Hf(3)S(14), Rb(4)Zr(3)Se(14),
      Cs(4)Zr(3)Se(14), and Cs(4)Hf(3)Se(14).
AB  - The alkali metal/group 4 metal/polychalcogenides Cs(4)Ti(3)Se(13),
      Rb(4)Ti(3)S(14), Cs(4)Ti(3)S(14), Rb(4)Hf(3)S(14), Rb(4)Zr(3)Se(14),
      Cs(4)Zr(3)Se(14), and Cs(4)Hf(3)Se(14) have been synthesized by means of the
      reactive flux method at 823 or 873 K. Cs(4)Ti(3)Se(13) crystallizes in a new
      structure type in space group C(2)(2)-P2(1) with eight formula units in a
      monoclinic cell at T = 153 K of dimensions a = 10.2524(6) A, b = 32.468(2) A, c =
      14.6747(8) A, beta = 100.008(1) degrees. Cs(4)Ti(3)Se(13) is composed of four
      independent one-dimensional [Ti(3)Se(13)(4-)] chains separated by Cs(+) cations.
      These chains adopt hexagonal closest packing along the [100] direction. The
      [Ti(3)Se(13)(4-)] chains are built from the face- and edge-sharing of pentagonal
      pyramids and pentagonal bipyramids. Formal oxidation states cannot be assigned in
      Cs(4)Ti(3)Se(13). The compounds Rb(4)Ti(3)S(14), Cs(4)Ti(3)S(14),
      Rb(4)Hf(3)S(14), Rb(4)Zr(3)Se(14), Cs(4)Zr(3)Se(14), and Cs(4)Hf(3)Se(14)
      crystallize in the K(4)Ti(3)S(14) structure type with four formula units in space
      group C(2)(h)()(6)-C2/c of the monoclinic system at T = 153 K in cells of
      dimensions a = 21.085(1) A, b = 8.1169(5) A, c = 13.1992(8) A, beta = 112.835(1)
      degrees for Rb(4)Ti(3)S(14);a = 21.329(3) A, b = 8.415(1) A, c = 13.678(2) A,
      beta = 113.801(2) degrees for Cs(4)Ti(3)S(14); a = 21.643(2) A, b = 8.1848(8) A,
      c = 13.331(1) A, beta = 111.762(2) degrees for Rb(4)Hf(3)S(14); a = 22.605(7) A,
      b = 8.552(3) A, c = 13.880(4) A, beta = 110.919(9) degrees for Rb(4)Zr(3)Se(14);
      a = 22.826(5) A, b = 8.841(2) A, c = 14.278(3) A, beta = 111.456(4) degrees for
      Cs(4)Zr(3)Se(14); and a = 22.758(5) A, b = 8.844(2) A, c = 14.276(3) A, beta =
      111.88(3) degrees for Cs(4)Hf(3)Se(14). These A(4)M(3)Q(14) compounds (A = alkali
      metal; M = group 4 metal; Q = chalcogen) contain hexagonally closest-packed
      [M(3)Q(14)(4-)] chains that run in the [101] direction and are separated by A(+)
      cations. Each [M(3)Q(14)(4-)] chain is built from a [M(3)Q(14)] unit that
      consists of two MQ(7) pentagonal bipyramids or one distorted MQ(8) bicapped
      octahedron bonded together by edge- or face-sharing. Each [M(3)Q(14)] unit
      contains six Q(2)(2-) dimers, with Q-Q distances in the normal single-bond range
      2.0616(9)-2.095(2) A for S-S and 2.367(1)-2.391(2) A for Se-Se. The A(4)M(3)Q(14)
      compounds can be formulated as (A(+))(4)(M(4+))(3)(Q(2)(2-))(6)(Q(2-))(2).

PMID- 11327912
TI  - Modeling platinum group metal complexes in aqueous solution.
AB  - We construct force fields suited for the study of three platinum group metals
      (PGM) as chloranions in aqueous solution from quantum chemical computations and
      report experimental data. Density functional theory (DFT) using the local density
      approximation (LDA), as well as extended basis sets that incorporate relativistic
      corrections for the transition metal atoms, has been used to obtain equilibrium
      geometries, harmonic vibrational frequencies, and atomic charges for the
      complexes. We found that DFT calculations of [PtCl(6)](2-).3H(2)O, [PdCl(4)](2
      ).2H(2)O, and [RhCl(6)](3-).3H(2)O water clusters compared well with molecular
      mechanics (MM) calculations using the specific force field developed here. The
      force field performed equally well in condensed phase simulations. A 500 ps
      molecular dynamics (MD) simulation of [PtCl(6)](2-) in water was used to study
      the structure of the solvation shell around the anion. The resulting data were
      compared to an experimental radial distribution function derived from X-ray
      diffraction experiments. We found the calculated pair correlation functions (PCF)
      for hexachloroplatinate to be in good agreement with experiment and were able to
      use the simulation results to identify and resolve two water-anion peaks in the
      experimental spectrum.

PMID- 11327913
TI  - Development of novel water-soluble, organometallic compounds for potential use in
      nuclear medicine: synthesis, characterization, and (1)H and (31)P NMR
      investigations of the complexes fac-[ReBr(CO)3L]
      (L=bis(bis(hydroxymethyl)phosphino)ethane,
      bis(bis(hydroxymethyl)phosphino)benzene).
AB  - The bidentate, water-soluble phosphine ligands,
      bis(bis(hydroxymethyl)phosphino)benzene (HMPB, 1) and
      bis(bis(hydroxymethyl)phosphino)ethane (HMPE, 2) were reacted with the
      organometallic precursor fac-[ReBr(3)(CO)(3)](2-), 3, to produce the complexes
      fac-[Re(OH(2))(CO)(3)L](+) and fac-[ReBr(CO)(3)L] (L = HMPE, HMPB), respectively,
      in good yields. The rhenium complexes fac-[ReBr(CO)(3)HMPB], 5, and fac-[
      ReBr(CO)(3)HMPE], 8, were characterized using (1)H and (31)P NMR spectroscopy.
      The structure of fac-[ReBr(CO)(3)HMPB] was confirmed by single-crystal X-ray
      spectroscopy. The substitution reactions of HMPE/HMPB with the rhenium precursor
      3 in aqueous solution were monitored using time-dependent (31)P NMR techniques. A
      significant discrepancy in the reaction kinetics and the substitution mechanism
      between the two bidentate ligands could be observed presumably due to the
      different chemical backbones.

PMID- 11327914
TI  - Syntheses and characterization of mu,eta(1),eta(1)-3,5-di-tert-butylpyrazolato
      derivatives of aluminum.
AB  - The 3,5-di-tert-butylpyrazolato (3,5-tBu(2)pz) derivatives of aluminum
      [(eta(1),eta(1)-3,5-tBu(2)pz)(mu-Al)R(1)R(2)](2) (R(1) = R(2) = Me 1; R(1) = R(2)
      = Et, 2; R(1) = R(2) = Cl, 3; R(1) = R(2) = I, 4; [(eta(2)-3,5-tBu(2)pz)(3)Al],
      5; [Al(2)(eta(1),eta(1)-3,5-tBu(2)pz)(2)(mu-E)(C triple bond CPh)(2)] (E = S (6),
      Se (7), Te (8)) have been prepared in good yield. Compounds 1 and 2 were obtained
      by the reactions of H[3,5-tBu(2)pz] with Me(3)Al and Et(3)Al, respectively.
      Reaction of [(eta(1),eta(1)-3,5-tBu(2)pz)(mu-Al)H(2)](2) with the pyrazole H[3,5
      tBu(2)pz] gave [(eta(2)-3,5-tBu(2)pz)(3)Al] (5). The reaction of [(eta(1),eta(1)
      3,5-tBu(2)pz)(mu-Al)R(2)](2) (R = H, Me) and I(2) yielded 4, while the reaction
      of 1 equiv of K[3,5-tBu(2)pz] and AlCl(3) afforded 3. In addition, the reaction
      of [Al(2)(eta(1),eta(1)-3,5-tBu(2)pz)(2)(mu-E)H(2)] and HC triple bond CPh gave
      6, 7, and 8. All compounds have been characterized by elemental analysis, NMR,
      and mass spectroscopy. The molecular structure analyses of compounds 1, 3, 6, and
      7 by X-ray crystallography showed that complexes 1 and 3 are dimeric with two
      eta(1),eta(1)-pyrazolato groups in twisted conformation while 6 and 7 with two
      eta(1),eta(1)-pyrazolato groups display a boat conformation.

PMID- 11327915
TI  - New selectivity in peptide hydrolysis by metal complexes. Platinum(II) complexes
      promote cleavage of peptides next to the tryptophan residue.
AB  - Tryptophan-containing N-acetylated peptides AcTrp-Gly, AcTrp-Ala, AcTrp-Val, and
      AcTrp-ValOMe bind to platinum(II) and undergo selective hydrolytic cleavage of
      the C-terminal amide bond; the N-terminal amide bond remains intact. In acetone
      solution, bidentate coordination of the tryptophanyl residue via the C(3) atom of
      indole and the amide oxygen atom produces complexes of spiro stereochemistry,
      which are characterized by (1)H, (13)C, and (195)Pt NMR spectroscopy, and also by
      UV-vis, IR, and mass spectroscopy. Upon addition of 1 molar equiv of water, these
      complexes undergo hydrolytic cleavage. This reaction is as much as 10(4)-10(5)
      times faster in the presence of platinum(II) complexes than in their absence. The
      hydrolysis is conveniently monitored by (1)H NMR spectroscopy. We report the
      kinetics and mechanism for this reaction between cis-[Pt(en)(sol)(2)](2+), in
      which the solvent ligand is water or acetone, and AcTrp-Ala. The platinum(II) ion
      as a Lewis acid activates the oxygen-bound amide group toward nucleophilic attack
      of solvent water. The reaction is unimolecular with respect to the metal-peptide
      complex. Because the tryptophanyl fragment AcTrp remains coordinated to
      platinum(II) after cleavage of the amide bond, the cleavage is not catalytic.
      Added ligand, such as DMSO and pyridine, displaces AcTrp from the platinum(II)
      complex and regenerates the promoter. This is the first report of cleavage of
      peptide bonds next to tryptophanyl residues by metal complexes and one of the
      very few reports of organometallic complexes involving metal ions and peptide
      ligands. Because these complexes form in nonaqueous solvents, a prospect for
      cleavage of membrane-bound and other hydrophobic proteins with new
      regioselectivity has emerged.

PMID- 11327917
TI  - Macrocyclic hydroperoxocobalt(III) complex: photochemistry, spectroscopy, and
      crystal structure.
AB  - The hydroperoxocobalt complex [L(2)(CH(3)CN)CoOOH](ClO(4))(2).CH(3)CN (L(2) =
      meso-5,7,7,12,14,14-Me(6)-[14]aneN(4)) crystallizes with discrete anions,
      cations, and solvate acetonitrile molecules in the lattice. The complex
      crystallizes in the monoclinic space group P2(1)/n, a = 10.4230(5) A, b =
      16.1561(8) A, c = 17.4676(9) A, beta = 92.267(1) degrees, V = 2939.2(3) A(3), Z =
      4. The O-O bond length is 1.397(4) A, and the O(2)-O(1)-Co angle spans 117.7
      degrees. The O-O stretch in the infrared spectrum appears at 815 cm(-1). The 355-
      and 266-nm photolysis of acidic aqueous solutions of L(2)(H(2)O)CoOOH(2+) results
      in homolytic splitting of the Co-O bond and yields L(2)Co(H(2)O)(2)(2+) and
      HO(2)(*)/O(2)(*-) as the only products. The two fragments were scavenged
      selectively in separate experiments with O(2) and C(NO(2))(4). There is no
      evidence for photochemical O-O bond homolysis, presumably because the appropriate
      optical transition is masked by the HO(2)-to-Co LMCT transition.

PMID- 11327916
TI  - Copper(II) azide complexes of aliphatic and aromatic amine based tridentate
      ligands: novel structure, spectroscopy, and magnetic properties.
AB  - Copper(II) azide complexes of three tridentate ligands namely 2,6-(3,5
      dimethylpyrazol-1-ylmethyl)pyridine (L), 2,6-(pyrazol-1-ylmethyl)pyridine (L'),
      and dipropylenetriamine (dpt) yield three kinds of complexes with different azide
      binding modes. The ligand L forms two end-on-end (mu-1,3) diazido-bridged
      binuclear complexes, [CuL(mu-N(3))](2)(ClO(4))(2) (1) and [CuL(mu
      N(3))(ClO(4))](2).2CH(3)CN (2), and L' forms a perchlorato-bridged quasi-one
      dimensional chain complex, [CuL'(N(3))(ClO(4))](n)() (3) with monodentate azide
      coordination. The ligation of dipropylenetriamine (dpt) gives a end-on (mu-1,1)
      diazido-bridged binuclear copper complex [Cu(dpt)(mu-N(3))](2)(ClO(4))(2) (4).
      The crystal and molecular structures of these complexes have been solved.
      Variable-temperature EPR results of 1 and 2 are identical and indicate the
      presence of both ferromagnetic and antiferromagnetic interactions within the
      dimer, the former dominating at low temperatures and the latter at high
      temperatures. The unusual temperature-dependent magnetic moment and EPR spectra
      of this dimer reveal the presence of temperature-dependent population of two
      triplet states, one being caused by antiferromagnetic and the other by
      ferromagnetic interaction, the former transforming to the latter on cooling.
      While the interaction of ground spin doublets of the two metal centers gives rise
      to a ferromagnetic coupling of J(g) = 90.73 cm(-1), the other coupling of J(e) = 
      185.64 cm(-1) is suggested to be caused by the interaction between an electron in
      one metal center and an electron from the azide of the other monomer by
      excitation of a d-electron to the empty ligand orbital. The ferromagnetic state
      is energetically favored by 104.39 cm(-1). Compound 3 exhibits axial spectra at
      room temperature and 77 K, and variable-temperature magnetic susceptibility data
      indicate that the copper centers form a weakly antiferromagnetic one-dimensional
      chain with J = -0.11 cm(-1). In the case of 4, the unique presence of two
      nonidentical dimeric units with different bond lengths and bond angles within the
      unit cell as inferred by crystal structure is proved by single-crystal EPR
      spectroscopy.

PMID- 11327918
TI  - Carboxy ester hydrolysis promoted by a zinc(II) 2-[bis(2
      aminomethyl)amino]ethanol complex: a new model for indirect activation on the
      serine nucleophile by zinc(II) in zinc enzymes.
AB  - A complexation study on the new Zn(II) complexes of asymmetric tripodal ligand 2
      [bis(2-aminoethyl)amino]ethanol (L) has revealed that the alcoholic OH group of
      complex ZnL exhibits remarkable acidity with a very low pK(a) value of 7.7 at 25
      degrees C. Both the monomeric complex [ZnH(-0.25)L(H(2)O)](ClO(4))(1.75) (I) and
      the dimeric alkoxide-coordinating complex [Zn(2)(H(-1)L)(2)](ClO(4))(2) (II) were
      synthesized, and their structures were determined by X-ray diffraction. The
      Zn(II)-bound alkoxide, as the reactive nucleophile toward the hydrolysis of
      esters, has shown a second-order rate constant of 0.13 +/- 0.01 M(-1) s(-1) in
      10% (v/v) CH(3)CN at 25 degrees C in 4-nitrophenyl acetate (NA) hydrolysis, which
      is almost the same as the corresponding value for the very reactive alcohol
      dependent [12]aneN(3)-Zn complex. Present work shows for the first time that
      Zn(II) complexes of the asymmetric tripodal polyamine bearing an ethoxyl pod can
      also serve as good models of Zn(II)-containing enzymes.

PMID- 11327919
TI  - Synthesis and structure of W(eta(2)-mp)(2)(CO)(3) (mp = monoanion of 2
      mercaptopyridine) and its reactions with 2,2'-pyridine disulfide and/or NO to
      yield W(eta(2)-mp)(4), W(eta(2)-mp)(2)(NO)(2), and W(eta(2)-mp)(3)(NO).
AB  - Oxidative addition of the sulfur-sulfur bond of 2,2'-pyridine disulfide
      (C(5)H(4)NS-SC(5)H(4)N) with L(3)W(CO)(3) [L = pyridine, (1)/(3)CHPT; CHPT =
      cycloheptatriene] in methylene chloride solution yields the seven-coordinate
      W(II) thiolate complex W(eta(2)-mp)(2)(CO)(3) (mp = monoanion of 2
      mercaptopyridine). This complex undergoes slow further oxidative addition with
      additional pyridine disulfide, yielding W(eta(2)- mp)(4). Reaction of W(eta(2)
      mp)(2)(CO)(3) with NO results in quantitative formation of the six-coordinate
      W(0) complex W(eta(2)-mp)(2)(NO)(2). Reaction of W(eta(2)-mp)(2)(CO)(3) with NO
      in the presence of added pyridine disulfide yields the seven-coordinate W(II)
      nitrosyl complex W(eta(2)-mp)(3)(NO) as well as W(eta(2)-mp)(2)(NO)(2) and trace
      amounts of W(eta(2)-mp)(4). The complex W(eta(2)-mp)(3)(NO) is formed during the
      course of the reaction and not by reaction of W(eta(2)-mp)(4) or W(eta(2)
      mp)(2)(NO)(2) with NO under these conditions. The crystal structures of W(eta(2)-
      mp)(2)(CO)(3), W(eta(2)-mp)(2)(NO)(2), and W(eta(2)-mp)(3)(NO) are reported.

PMID- 11327920
TI  - Synthesis and characterization of four new europium group XIV chalcogenides:
      K(2)EuTSe(5) and KEuTS(4) (T = Si, Ge).
AB  - Four europium group XIV chalcogenides have been synthesized using the reactive
      flux method: K(2)EuTSe(5) (I, II) and KEuTS(4) (III, IV) where T = Si, Ge.
      K(2)EuSiSe(5), I, crystallizes in the monoclinic space group P2(1)/c with cell
      parameters a = 11.669(3) A, b = 9.844(2) A, c = 8.917(2) A, beta = 91.583(5)
      degrees, and Z = 4. K(2)EuGeSe(5), II, crystallizes in the monoclinic space group
      P2(1)/c with cell parameters a = 11.8056(3) A, b = 9.9630(1) A, c = 8.9456(1) A,
      beta = 91.195(1) degrees, and Z = 4. Both K(2)EuSiSe(5) and K(2)EuGeSe(5) are
      semiconductors with optical band-gaps of approximately 2.00 and 1.84 eV,
      respectively. Raman spectroscopy shows vibrations from the (TSe(5))(4-) (T = Si,
      Ge) unit. KEuSiS(4), III, crystallizes in the monoclinic space group P2(1) with
      cell parameters a = 6.426(4) A, b = 6.582(5) A, c = 8.566(7) A, beta = 107.83(6)
      degrees, and Z = 2. KEuGeS(4), IV, crystallizes in the monoclinic space group
      P2(1) with cell parameters a = 6.510(2) A, b = 6.649(2) A, c = 8.603(3) A, beta =
      107.80(2) degrees, and Z = 2. Band-gap analysis shows that both compounds are
      semiconductors with optical band-gaps of 1.72 and 1.71 eV, respectively. The
      Raman spectrum of KEuGeS(4) shows the vibrations of the (GeS(4))(4-) unit.
      Fluorescence spectroscopy confirms the presence of Eu(III) in III and IV instead
      of Eu(II) as in I and II. These four crystalline products were formed under
      equivalent stoichiometric reaction conditions. The fact that two different
      products are observed can be used to understand the relationship between the
      oxidative and reductive potentials within these flux reactions.

PMID- 11327921
TI  - Novel synthesis of ClF(6)(+) and BrF(6)(+) salts.
AB  - For a compound in a given oxidation state, its oxidizing strength increases from
      its anion to the neutral parent molecule to its cation. Similarly, an anion is
      more easily oxidized than its neutral parent molecule, which in turn is more
      easily oxidized than its cation. This concept was systematically exploited in our
      search for new superoxidizers. Transition metal fluoride anions were prepared in
      their highest known oxidation states by high temperature/high pressure
      fluorinations with elemental fluorine and subsequently converted to their more
      strongly oxidizing cations by a displacement reaction with a strong Lewis acid.
      The application of this principle resulted in new syntheses for ClF(6)(+)AsF(6)(
      ) and BrF(6)(+)AsF(6)(-) using the highly reactive and thermally unstable
      NiF(3)(+) cation that was prepared from the reaction of the NiF(6)(2)(-) anion
      with AsF(5) in anhydrous HF. Attempts to prepare the known KrF(+) and
      ClO(2)F(2)(+) cations and the yet unknown XeF(7)(+) cation by the same method
      were unsuccessful. The results from this and previous studies show that NiF(3)(+)
      is a stronger oxidative fluorinator than PtF(6), but whether its oxidizing
      strength exceeds that of KrF(+) remains unclear. Its failure to oxidize Kr to
      KrF(+) might have been due to unfavorable reaction conditions. Its failure to
      oxidize ClO(2)F to ClO(2)F(2)(+), in spite of its favorable oxidizer strength, is
      attributed to the high Lewis basicity of ClO(2)F which results in a rapid
      displacement reaction of NiF(3)(+) by ClO(2)F, thus generating the weaker
      oxidizer NiF(4) and the more difficult to oxidize substrate ClO(2)(+). Therefore,
      the general applicability of this approach appears to be limited to substrates
      that exhibit a weaker Lewis basicity than the neutral transition metal parent
      molecule. Compared to KrF(+)- or PtF(6)-based oxidations, the NiF(3)(+) system
      offers the advantages of commercially available starting materials and higher
      yields, but product purification can be more difficult and tedious than for
      KrF(+).

PMID- 11327922
TI  - Tetrakis[(mu-hydroxo)(mu-sulfathiazolato)copper(II)] tetrakis(dimethyl
      sulfoxide): a new square-planar tetranuclear copper(II) complex containing four
      hydroxo and four NCN-sulfathiazolato bridges. Electrochemical synthesis, crystal
      structure, and magnetic properties.

PMID- 11327923
TI  - Synthesis of the titanium compound [(MeC(5)H(4)TiCl(mu-NSiMe(3)](2) with
      migration of a SiMe(3) group and preparation of CpZrCl(eta(2)-NHNCHSiMe(3)).

PMID- 11327924
TI  - Organotitanoxanes [C(5)Me(5)TiMe(2)](2)(mu-O) and [(C(5)Me(5)(4)Ti(4)Me(2)](mu
      O)(5): synthesis and crystal structures.

PMID- 11327925
TI  - Coordination polymers from M(hfac)(2) [M = Cu(II), Mn(II)] and 4,4'
      dipyridyldisulfide.

PMID- 11327926
TI  - Magnetic properties and redox isomerism for 4,4'-bis(semiquinone) complexes of
      copper.

PMID- 11327927
TI  - Synthesis, structure, and catalytic reactivity of N,N,S- and O,N,S-tridentate
      oxorhenium(V) complexes.

PMID- 11327929
TI  - Preparation and characterization of a tetranuclear and mixed-valence
      Nb(II)/Nb(III) diamagnetic Nb(4)Cl(12)Li(2)(THF)(8) cluster.

PMID- 11327928
TI  - Raman and extended X-ray absorption fine structure characterization of a sulfur
      ligated Cu(I) ethylene complex: modeling the proposed ethylene binding site of
      Arabidopsis thaliana ETR1.

PMID- 11327930
TI  - Synthesis of a spin-coupled, mixed-metal double square grid complex [(poap
      H)(4)Cu(II)(3)Fe(III)-(NO(3))](2)(ClO(4))(4)(NO(3))(4).12H(2)O (poap = N(3)-(2
      pyridoyl)-2-pyridinecarboxamidrazone) with an S = 3 ground state, from a
      mononuclear Fe(III) precursor complex.

PMID- 11327931
TI  - Distortions from octahedral symmetry in hypoelectronic six-vertex polyhedral
      clusters of the group 13 elements boron, indium, and thallium as studied by
      density functional theory.

PMID- 11327932
TI  - Calculational study of the protonation of BXH(2) and BX(2)H (X = F and Cl).
      structures of BXH(3)(+) and BX(2)H(2)(+) and their dihydrogen complexes BXH(5)(+)
      and BX(2)H(4)(+).

PMID- 11327933
TI  - Polymorphism in bis(4-dimethylamino-pyridinium)tetrachlorocuprate(II).

PMID- 11327934
TI  - Aromatic and benzylic C-H bond activation in the system bis(dicarbonylrhodium(I))
      porphyrinate--hydrocarbon solvent.

PMID- 11327935
TI  - Quantum backreaction through the Bohmian particle.
AB  - A novel solution to the quantum backreaction problem in a mixed quantum-classical
      simulation is provided using the Bohmian interpretation of quantum mechanics. The
      Bohmian backreaction is unique, computationally simple, features reaction channel
      branching, and easily gives the full classical limit. The Bohmian quantum
      classical method is illustrated by application to a model of O2 interacting with
      a Pt surface.

PMID- 11327936
TI  - Quantum superchemistry: dynamical quantum effects in coupled atomic and molecular
      Bose-Einstein condensates.
AB  - We show that in certain parameter regimes there is a macroscopic dynamical
      breakdown of the Gross-Pitaevskii equation. Stochastic field equations for
      coupled atomic and molecular condensates are derived using the functional
      positive- P representation. These equations describe the full quantum state of
      the coupled condensates and include the commonly used Gross-Pitaevskii equation
      as the noiseless limit. The full quantum theory includes the spontaneous
      processes which will become significant when the atomic population is low. The
      experimental signature of the quantum effects will be the time scale of the
      revival of the atomic population after a near total conversion to the molecular
      condensate.

PMID- 11327937
TI  - Grand unification signal from ultrahigh energy cosmic rays?
AB  - The spectrum of ultrahigh energy (above approximately 10(9) GeV) cosmic rays is
      consistent with the decay of grand unification scale particles. The predicted
      mass is m(X) = 10(b) GeV, where b = 14.6(+1.6)(-1.7).

PMID- 11327941
TI  - 12C(alpha,gamma)16O: the key reaction in stellar nucleosynthesis.
AB  - The angular distributions of gamma rays from the 12C(alpha,gamma)16O reaction
      have been measured at 20 energy points in the energy range E(cm) = 0.95 to 2.8
      MeV. The sensitivity of the present experiment compared to previous direct
      investigations was raised by 1-2 orders of magnitude, by using an array of highly
      efficient ( 100%) Ge detectors shielded actively with BGOs, as well as high beam
      currents of up to 500 microA that were provided by the Stuttgart Dynamitron
      accelerator. The S(E1) and S(E2) factors deduced from the gamma angular
      distributions have been extrapolated to the range of helium burning temperatures
      applying the R-matrix method, which yielded S(300)(E1) = (76+/-20) keV b and
      S(300)(E2) = (85+/-30) keV b.

PMID- 11327942
TI  - Predicting total reaction cross sections for nucleon-nucleus scattering.
AB  - Nucleon total reaction and neutron total cross sections to 300 MeV for 12C and
      208Pb, and for 65 MeV scattering spanning the mass range, are predicted using
      coordinate space optical potentials formed by full folding of effective nucleon
      nucleon interactions with realistic nuclear ground state densities. Good to
      excellent agreement is found with existing data.

PMID- 11327940
TI  - Measurement of the branching ratio and asymmetry of the decay Xi degrees -->Sigma
      degrees gamma.
AB  - We have studied the rare weak radiative hyperon decay Xi degrees -->Sigma degrees
      gamma in the KTeV experiment at Fermilab. We have identified 4045 signal events
      over a background of 804 events. The dominant Xi degrees -->Lambdapi degrees
      decay, which was used for normalization, is the only important background source.
      An analysis of the acceptance of both modes yields a branching ratio of B(Xi
      degrees -->Sigma degrees gamma)/B(Xi degrees -->Lambdapi degrees ) = (3.34+/
      0.05+/-0.09)x10(-3). By analyzing the final state decay distributions, we have
      also determined that the Sigma degrees emission asymmetry parameter for this
      decay is alpha(XiSigma) = -0.63+/-0.09.

PMID- 11327943
TI  - Evidence for spinodal decomposition in nuclear multifragmentation.
AB  - Multifragmentation of a "fused system" was observed for central collisions
      between 32 MeV/nucleon 129Xe and (nat)Sn. Most of the resulting charged products
      were well identified due to the high performances of the INDRA 4pi array.
      Experimental higher-order charge correlations for fragments show a weak but
      nonambiguous enhancement of events with nearly equal-sized fragments. Supported
      by dynamical calculations in which spinodal decomposition is simulated, this
      observed enhancement is interpreted as a "fossil" signal of spinodal
      instabilities in finite nuclear systems.

PMID- 11327938
TI  - Measurement of B(0)(d)-B_(0)(d) mixing rate from the time evolution of dilepton
      events at the upsilon(4S).
AB  - We report a determination of the B(0)(d)-&B_(0)(d) mixing parameter Deltam(d)
      based on the time evolution of dilepton yields in Upsilon(4S) decays. The
      measurement is based on a 5.9 fb(-1) data sample collected by the Belle detector
      at KEKB. The proper-time difference distributions for same-sign and opposite-sign
      dilepton events are simultaneously fitted to an expression containing Deltam(d)
      as a free parameter. Using both muons and electrons, we obtain Deltam(d) =
      0.463+/-0.008 (stat)+/-0.016 (syst) ps(-1). This is the first determination of
      Deltam(d) from time evolution measurements at the Upsilon(4S). We also place
      limits on possible CPT violations.

PMID- 11327945
TI  - High-accuracy calculation of 6s --> 7s parity-nonconserving amplitude in Cs.
AB  - We calculated the parity-nonconserving (PNC) 6s-->7s amplitude in Cs. In the
      Dirac-Coulomb approximation our result is in good agreement with other
      calculations. Breit corrections to the PNC amplitude and to the Stark-induced
      amplitude beta are found to be -0.4% and -1%, respectively. The weak charge of
      133Cs is Q(W) = -72.5+/-0.7 in agreement with the standard model.

PMID- 11327944
TI  - Exchange forces in dispersion relations investigated using circuit relations.
AB  - We propose a novel method to compute in an exact manner the left-hand cut
      discontinuity of the electron-atom partial wave scattering amplitude in the
      complex energy plane within the static exchange approximation. Zero energy
      dispersion relations for electron-hydrogen scattering are computed numerically
      for illustration.

PMID- 11327946
TI  - Energy transport in high-density spin-exchange optical pumping cells.
AB  - We present in situ measurements of temperatures inside multi-atmosphere spin
      exchange optical pumping cells using Raman scattering from the N2 quenching gas.
      Under conditions usually prevailing in spin-exchange optical pumping experiments,
      we find that gas temperatures can be elevated hundreds of degrees above ambient,
      and that convection plays a very important role in the heat transport of the
      system.

PMID- 11327947
TI  - Magnetic-field-induced quadrupole splitting in gaseous and liquid 131Xe NMR:
      quadratic and quartic field dependence.
AB  - A theory for the magnetic-field-dependent quadrupole splitting in the 131Xe NMR
      spectra in isotropic media is presented and tested by ab initio electronic
      structure calculations. Evidence exists only for even-power magnetic field
      dependence. The dominant mechanism is verified to be the electric field gradient
      caused by the diamagnetic distortion of the atomic electron cloud, quadratic in
      the magnetic field. The computed results are in excellent agreement with the
      recent experiment by Meersmann and Haake.

PMID- 11327948
TI  - Observation of direct dissociative ionization in molecular hydrogen.
AB  - Direct dissociative ionization is the simplest three-body breakup process in H2.
      We describe the experimental verification of direct dissociative ionization to
      the repulsive A2Sigma(+)(u) state by resolving the kinetic energy and angular
      distributions of the formed protons. A (2+1) resonant enhanced multiphoton
      ionization process via the isotropic E,F (1)Sigma(+)(g)(v = 6,J = 0) level is
      employed. The structure in the kinetic energy spectrum is well described by a
      projection of the vibrational wave function of the E,F (1)Sigma(+)(g)(v = 6,J =
      0) state onto the repulsive ionic state. The electronic character of the
      ionization continuum is revealed by the proton angular distribution.

PMID- 11327949
TI  - Triplet scattering lengths for rubidium and their role in Bose-Einstein
      condensation.
AB  - The triplet scattering lengths of 85Rb and 87Rb are evaluated as a function of C6
      using a potential whose short-range form is fitted to an ab initio result. This
      is combined with a previous analysis of photoassociation measurements, which
      allows the determination of bounds on C6 and the scattering amplitudes to give
      sharper bounds for these quantities. Questions are raised about the use of
      scattering length as the sole atomic parameter in the description of Bose
      Einstein condensates.

PMID- 11327950
TI  - New value of m(mu)/m(e) from muonium hyperfine splitting.
AB  - The complete contribution to the muonium hyperfine splitting of relative order
      alpha(3)(m(e)/m(mu))lnalpha is calculated. The result is much smaller than
      suggested by a previous estimate and leads to a 2sigma upward shift of the most
      precise value for the muon-electron mass ratio. Analogous contributions are
      calculated for the positronium hyperfine splitting, where a discrepancy with
      experiment remains.

PMID- 11327951
TI  - First experimental test of a trace formula for billiard systems showing mixed
      dynamics.
AB  - In general, trace formulas relate the density of states for a given quantum
      mechanical system to the properties of the periodic orbits of its classical
      counterpart. Here we report for the first time on a semiclassical description of
      microwave spectra taken from superconducting billiards of the Limacon family
      showing mixed dynamics in terms of a generalized trace formula derived by Ullmo
      et al. [Phys. Rev. E 54, 136 (1996)]. This expression not only describes mixed
      typed behavior but also the limiting cases of fully regular and fully chaotic
      systems and thus presents a continuous interpolation between the Berry-Tabor and
      Gutzwiller formulas.

PMID- 11327952
TI  - Stabilization of femtosecond lasers for optical frequency metrology and direct
      optical to radio frequency synthesis.
AB  - We have actively stabilized the comb of frequencies from a mode-locked
      femtosecond laser using a Fabry-Perot reference cavity. This technique offers the
      ability to synthesize a comb of highly stable radio frequencies directly from
      optical transitions. The measured fractional frequency instability of the
      components of the frequency comb relative to the reference cavity was <5x10(-13)
      in 0.1 sec. The variation of the optical mode spacing versus frequency of the
      reference cavity was also directly measured using this technique.

PMID- 11327953
TI  - Extreme midinfrared nonlinear optics in semiconductors.
AB  - We have observed extreme nonlinear optical phenomena produced by intense
      midinfrared (MIR) pulses in semiconductors. These phenomena include multiple off
      resonance optical sidebands (up to +/-3 MIR photons interacting with a near
      infrared photon), multiple MIR harmonics (up to the seventh harmonic), and
      significant broadening and modification of MIR harmonic spectra. The generation
      of these extreme MIR nonlinear optical phenomena is primarily aided by cross
      phase modulation.

PMID- 11327954
TI  - Self-focusing and defocusing in waveguide arrays.
AB  - We show that two regimes of diffraction exist in arrays of waveguides, depending
      upon the input conditions. At higher powers, normal diffraction leads to self
      focusing and to the formation of bright solitons through the nonlinear Kerr
      effect. By slightly changing the input conditions, light experiences anomalous
      diffraction and is nonlinearly defocused. For the first time, self-focusing and
      self-defocusing have been achieved for the same medium, structure, and
      wavelength.

PMID- 11327955
TI  - Settling statistics of hard sphere particles.
AB  - Direct imaging of settling, non-Brownian, hard sphere, particles allows
      measurement of particle occupancy statistics as a function of time and sampling
      volume dimension. Initially random relative particle number fluctuations, <N2
      <N>(2)>/<N> = 1, become suppressed, anisotropic, and <N> dependent. Fitting to a
      simple Gaussian pair correlation model suggests a minute long ranged correlation
      leads to strong if not complete suppression of number fluctuations. Calflisch and
      Luke predict a divergence in velocity fluctuations with increasing sample volume
      size based on random (Poisson) statistics. Our results suggest this is not a
      valid assumption for settling particles.

PMID- 11327956
TI  - Convection in highly fluidized three-dimensional granular beds.
AB  - Free, buoyancy-driven convection has been observed experimentally in three
      dimensional highly fluidized granular flows for the first time. Positron emission
      particle tracking was used to determine the position of a tracer grain in a
      vibrofluidized bed, from which packing fraction distributions as well as the
      velocity fields could be determined. The convection rolls, although small
      compared to the magnitude of velocity fluctuations (<5%), were consistently
      observed for a range of grain numbers and shaker amplitudes. Density variations
      are a signature of free convection and, with negative temperature gradients also
      present, were interpreted as the mechanism by which the convection rolls were
      initiated.

PMID- 11327939
TI  - First measurement of the ratio B(t --> Wb)/B(t --> Wq) and associated limit on
      the Cabibbo-Kobayashi-Maskawa element /V(tb)/.
AB  - We present the first measurement of the ratio of branching fractions R identical
      withB(t-->Wb)/B(t-->Wq) from p_p collisions at sqrt[s] = 1.8 TeV. The data set
      corresponds to 109 pb(-1) of data recorded by the Collider Detector at Fermilab
      during the 1992-95 Tevatron run. We measure R = 0.94(+0.31)(-0.24)(stat+syst) or
      R>0.61 (0.56) at 90% (95)% C.L., in agreement with the standard model
      predictions. This measurement yields a limit on the Cabibbo-Kobayashi-Maskawa
      quark mixing matrix element /V(tb)/ under the assumption of three generations and
      unitarity.

PMID- 11327957
TI  - Green's function probe of a static granular piling.
AB  - We present an experiment which aims to investigate the mechanical properties of a
      static granular assembly. The piling is a horizontal 3D granular layer confined
      in a box. We apply a localized extra force at the surface and the spatial
      distribution of stresses at the bottom is obtained (the mechanical Green's
      function). For different types of granular media, we observe a linear pressure
      response whose profile shows one peak centered at the vertical of the point of
      application. The peak's width increases linearly with increasing depth. This
      Green's function seems to be in at least qualitative agreement with predictions
      of elastic theory.

PMID- 11327958
TI  - Static friction between elastic solids due to random asperities.
AB  - Several workers have established that the Larkin domains for two three
      dimensional nonmetallic elastic solids in contact with each other at a disordered
      but atomically flat interface are enormously large, implying that there should be
      negligible static friction per unit area in the macroscopic solid limit. In
      contrast, the present Letter argues that when the Larkin domains are calculated
      for disorder on the multiasperity scale, they are much smaller than the interface
      size. This can account for the virtual universal occurrence of static friction.

PMID- 11327959
TI  - Thermal convection for large Prandtl numbers.
AB  - The Rayleigh-Benard theory by Grossmann and Lohse [J. Fluid Mech. 407, 27 (2000)]
      is extended towards very large Prandtl numbers Pr. The Nusselt number Nu is found
      here to be independent of Pr. However, for fixed Rayleigh numbers Ra a maximum in
      the Nu(Pr) dependence is predicted. We moreover offer the full functional
      dependences of Nu(Ra,Pr) and Re(Ra,Pr) within this extended theory, rather than
      only give the limiting power laws as done in J. Fluid. Mech. 407, 27 (2000). This
      enables us to more realistically describe the transitions between the various
      scaling regimes.

PMID- 11327960
TI  - Prandtl-number dependence of heat transport in turbulent Rayleigh-Benard
      convection.
AB  - We present measurements of the Nusselt number N as a function of the Rayleigh
      number R and the Prandtl number sigma in cylindrical cells with aspect ratios
      gamma = 0.5 and 1.0. We used acetone, methanol, ethanol, and 2-propanol with
      Prandtl numbers sigma = 4.0, 6.5, 14.2, and 34.1, respectively, in the range
      3x10(7) less, similarR less, similar10(11). At constant R, N(R,sigma) varies with
      sigma by only about 2%. This result disagrees with the extrapolation of the
      Grossmann and Lohse theory beyond its range of validity, which implies a decrease
      by 20% over our sigma range, but agrees with their recent extension of the theory
      to small Reynolds numbers.

PMID- 11327961
TI  - New mechanism of x-ray radiation from a relativistic charged particle in a
      dielectric random medium.
AB  - Based on the diffusional scattering of pseudophotons, we propose a new mechanism
      of x-ray radiation from a relativistic charged particle moving in a system
      consisting of microspheres distributed randomly in a dielectric material. The
      mechanism leads to a stronger dependence of radiation intensity on the particle
      energy, gamma = E/mc(2), than that predicted by the transition radiation, and
      explains recent experimental data from a detector which contains randomly
      distributed superconducting granules.

PMID- 11327962
TI  - Parametric excitations of fast plasma waves by counterpropagating laser beams.
AB  - Short- and long-wavelength plasma waves can become strongly coupled in the
      presence of two counterpropagating laser pump pulses detuned by twice the cold
      plasma frequency omega(p). What makes this four-wave interaction important is
      that the growth rate of the plasma waves occurs much faster than in the more
      obvious copropagating geometry.

PMID- 11327963
TI  - Plasma ions dynamics in the wake of a short laser pulse.
AB  - A new physical effect of a plasma channel formation by the ponderomotive force of
      a wakefield generated by a laser pulse with a length of the order of the electron
      plasma wavelength is discussed. For a narrow pulse, wherein the width is less
      than c/omega(pe) ( omega(pe) and c are the plasma frequency and light velocity,
      respectively), the channel has an annular form with on-axis density maximum. The
      depth of the channel increases with the distance from the pulse until the phase
      mixing arises and the wake starts to break. The linear fluid theory is used to
      obtain the scaling for wave-breaking conditions. The results of numerical
      simulations for high intensity laser pulses are in good agreement with
      theoretical predictions.

PMID- 11327964
TI  - Stagnation pressure of imploding shells and ignition energy scaling of inertial
      confinement fusion targets.
AB  - The stagnation pressure p(s) of imploding cylindrical ( n = 2) and spherical ( n
      = 3) shells is found to scale as p(s)/p(0)~M(2(n+1)/(gamma+1))(0), where M0 is
      the Mach number of the imploding shell and p(0) its maximum pressure. The result
      holds approximately for Mach numbers in the range 2<M0<25 relevant for inertial
      confinement fusion capsules and is of key importance for their ignition energy
      scaling. It is derived analytically on the basis of similarity solutions for an
      ideal gas with adiabatic exponent gamma.

PMID- 11327965
TI  - Observation of a topological relaxation mode in microemulsions.
AB  - We report the observation of two diffusive relaxation modes in a very swollen
      microemulsion, measured by quasielastic light scattering experiments. In addition
      to a short-time diffusion process, we observe a long-time diffusive relaxation
      mode with unusual scaling behavior: the diffusion constant D is an exponential
      function of the characteristic length scale xi, D~exp(-xi). This observation
      provides experimental evidence for thermally activated topological relaxation of
      random fluid phases, as predicted by Milner et al. [J. Phys. (Paris) 51, 2629
      (1990)]. We describe the activation energy of such a process by some simple
      microscopic model for the surfactant layer and give an estimation of the membrane
      elastic and Gaussian moduli kappa and kappa;, and its spontaneous curvature.

PMID- 11327966
TI  - Velocity correlations and the structure of nonequilibrium hard-core fluids.
AB  - A model for the pair-distribution function of nonequilibrium hard-core fluids is
      proposed based on a model for the effect of velocity correlations on the
      structure. Good agreement is found with molecular dynamics simulations of
      granular fluids and of sheared elastic hard spheres. It is argued that the
      incorporation of velocity correlations are crucial to correctly modeling atomic
      scale structure in nonequilibrium fluids.

PMID- 11327967
TI  - Vacancy hardening and softening in transition metal carbides and nitrides.
AB  - The effects of vacancies on mechanical properties of the transition metal
      carbides and nitrides are studied using the ab initio pseudopotential approach.
      Calculated shear elastic stiffness and electronic structures show that the
      vacancy produces entirely different effects on the mechanical strength of groups
      IVb nitrides and Vb carbides. It is found that the occupation of shear-unstable
      metallic dd bonding states changes essentially in an opposite way for the
      carbides and nitrides in the presence of vacancies, resulting in different
      responses to shear stress. Our study provides an atomistic understanding of the
      anomaly in hardness for these substoichiometric materials.

PMID- 11327968
TI  - Microstructural stability of the Kirkendall plane in solid-state diffusion.
AB  - In a diffusion-controlled interaction, the Kirkendall plane, as marked by inert
      particles placed at the original contact surface of a reaction couple, need not
      be unique. Multiple planes can develop, and sometimes the Kirkendall plane does
      not exist at all. A phenomenological approach is introduced to rationalize the
      Kirkendall-effect-mediated migration of macroscopic inclusions inside a diffusion
      zone.

PMID- 11327969
TI  - Adsorption and two-body recombination of atomic hydrogen on 3He-4He mixture
      films.
AB  - We present the first systematic measurement of the binding energy E(a) of
      hydrogen atoms to the surface of saturated 3He- 4He mixture films at temperatures
      70-400 mK. E(a) is found to decrease almost linearly from 1.14(1) K down to
      0.39(1) K, when the population of the ground surface state of 3He grows from zero
      to 6x10(14) cm(-2), yielding the value 1.2(1)x10(-15) K cm(2) for the mean-field
      parameter of H- 3He interaction in 2D. Measuring by ESR the rate constants K(aa)
      and K(ab) for second-order recombination of hydrogen atoms in hyperfine states a
      and b, we find the ratio K(ab)/K(aa) to be independent of the 3He content and to
      grow with temperature.

PMID- 11327970
TI  - Helium in one-dimensional nanopores: free dispersion, localization, and
      commensurate/incommensurate transitions with nonrigid orbitals.
AB  - The single-particle states of helium within a bundle of carbon nanotubes can
      range from nearly free-particle dispersion to localization, even within a single
      bundle. At intermediate effective masses, the corrugation in the external
      potential can be comparable to the intrasite He-He hard-core interaction. This
      results in a commensurate/incommensurate transition, where the mobility of the
      doubly occupied domain-wall solitons at high density greatly exceeds the
      corresponding hole mobility below the transition.

PMID- 11327971
TI  - Commensurate water monolayer at the RuO2(110)/water interface.
AB  - We demonstrate the presence of two types of commensurate, registered water
      monolayers with different densities at the RuO2(110)/bulk-water (0.1 M NaOH
      solution) interface with off-specular, oxygen crystal truncation rods. At anodic
      potentials (close to oxygen evolution), the extraneous water layer and the
      surface hydroxide layer form a bilayer with O-H-O bond distances similar to that
      of ice X. At cathodic potentials, the water molecules converted from the bridging
      OH molecules form a low-density water layer.

PMID- 11327972
TI  - Scanning tunneling microscopy studies of temperature-dependent etching of diamond
      (100) by atomic hydrogen.
AB  - We present a technique for obtaining atomic resolution ultrahigh vacuum scanning
      tunneling microscopy images of diamond (100) films, and use this technique to
      study the temperature dependence of the etching of epitaxial diamond (100) films
      by atomic hydrogen. We find that etching by atomic hydrogen is highly temperature
      dependent, resulting in a rough and pitted surface at T approximately 200 and 500
      degrees C, respectively. At T approximately 1000 degrees C etching results in a
      smooth surface and is highly anisotropic, occurring predominantly in the
      direction of dimer rows. This observation supports recent theoretical models that
      propose anisotropic etching as the mechanism for the growth of smooth diamond
      (100) films.

PMID- 11327973
TI  - Polarons in carbon nanotubes.
AB  - We use ab initio total-energy calculations to predict the existence of polarons
      in semiconducting carbon nanotubes (CNTs). We find that the CNTs' band edge
      energies vary linearly and the elastic energy increases quadratically with both
      radial and with axial distortions, leading to the spontaneous formation of
      polarons. Using a continuum model parametrized by the ab initio calculations, we
      estimate electron and hole polaron lengths, energies, and effective masses and
      analyze their complex dependence on CNT geometry. Implications of polaron effects
      on recently observed electro- and optomechanical behavior of CNTs are discussed.

PMID- 11327974
TI  - Radio-frequency single-electron transistor as readout device for qubits: charge
      sensitivity and backaction.
AB  - We study the radio-frequency single-electron transistor (rf-SET) as a readout
      device for charge qubits. We measure the charge sensitivity of an rf-SET to be
      6.3microe/sqrt[Hz] and evaluate the backaction of the rf-SET on a single Cooper
      pair box. This allows us to compare the needed measurement time with the mixing
      time of the qubit imposed by the measurement. We find that the mixing time can be
      substantially longer than the measurement time, which would allow readout of the
      state of the qubit in a single shot measurement.

PMID- 11327975
TI  - Conductance peak motion due to a magnetic field in weakly coupled chaotic quantum
      dots.
AB  - We study the influence of moderate exchange interactions on the behavior of the
      peaks in the conductance of single electron transistors. We numerically reproduce
      recently observed features of the magnetic field dependence of both the peak
      positions and heights. These features unambiguously identify the total spin S of
      each ground state. We evaluate the probability of each S as a function of the
      exchange strength J, and external magnetic field B. The expressions involve only
      J and the g factor as adjustable parameters. For a broad parameter range these
      probabilities are determined by a linear combination of J and gB.

PMID- 11327976
TI  - Imaging of Friedel oscillation patterns of two-dimensionally accumulated
      electrons at epitaxially grown InAs(111) A surfaces.
AB  - The local density of states (LDOS) at the epitaxially grown InAs surface on a
      GaAs(111) A substrate were characterized using low-temperature scanning tunneling
      microscopy. Using dI/dV signal mapping, LDOS standing waves were clearly imaged
      at point defects and within nanostructures. Measurement of the wavelength as a
      function of bias voltage showed a nonparabolic dispersion relation for the
      conduction band. The observed wave features originate from the Friedel
      oscillations of the two-dimensional electron gas in the semiconductor surface
      accumulation layer.

PMID- 11327977
TI  - Radio-frequency Bloch-transistor electrometer.
AB  - A quantum electrometer is proposed which is based on charge modulation of the
      Josephson supercurrent in the Bloch transistor inserted in a superconducting
      ring. As this ring is inductively coupled to a high- Q resonance tank circuit,
      the variations of the charge on the transistor island are converted into
      variations of amplitude and phase of oscillations in the tank. These variations
      are amplified and then detected. At sufficiently low temperature of the tank the
      device sensitivity is determined by the energy resolution of the amplifier, that
      can be reduced down to the standard quantum limit of 1 / 2Planck's over 2pi. A
      "back-action-evading" scheme of subquantum limit measurements is proposed.

PMID- 11327978
TI  - Spinon attraction in spin- 1/2 antiferromagnetic chains.
AB  - We derive the representation of the two-spinon wave function for the Haldane
      Shastry model in terms of the spinon coordinates. This result allows us to
      rigorously analyze spinon interaction and its physical effects. We show that
      spinons attract one another. The attraction gets stronger as the size of the
      system is increased and, in the thermodynamic limit, determines the power law
      with which the susceptibility diverges.

PMID- 11327979
TI  - Nagaoka ferromagnetism in the two-dimensional infinite-U Hubbard model.
AB  - We present different numerical calculations based on variational quantum Monte
      Carlo simulations supporting a ferromagnetic ground state for finite and small
      hole densities in the two-dimensional infinite-U Hubbard model. Moreover, by
      studying the energies of different total spin sectors, these calculations
      strongly suggest that the paramagnetic phase is unstable against a phase with a
      partial polarization for large hole densities delta approximately 0.40 with
      evidence for a second-order transition to the paramagnetic large doping phase.

PMID- 11327980
TI  - Hamiltonian of the V15 spin system from first-principles density-functional
      calculations.
AB  - We report first-principles all-electron density-functional-based studies of the
      electronic structure, magnetic ordering, and anisotropy for the V15 molecular
      magnet. From these calculations, we determine a Heisenberg Hamiltonian with five
      antiferromagnetic and one ferromagnetic exchange couplings. We perform direct
      diagonalization to determine the temperature dependence of the susceptibility.
      This Hamiltonian reproduces the experimentally observed spin S = 1/2 ground state
      and low-lying S = 3/2 excited state. A small anisotropy term is necessary to
      account for the temperature independent part of the magnetization curve.

PMID- 11327981
TI  - Giant dielectric permittivity observed in pb-based perovskite ferroelectrics.
AB  - Giant dielectric permittivity was observed in La-modified PbTiO (3) (PLT) with A
      site vacancy. The observed values of PLT with A-site vacancy are 1 order of
      magnitude larger than those of relaxor ferroelectrics. The giant relative
      dielectric permittivity, coupled with a low dielectric loss (tandelta
      approximately 0.03) of the PLT, potentially makes it one of the most promising
      materials for numerous modern technological applications.

PMID- 11327982
TI  - Infrared and optical spectroscopy of alpha- and gamma-phase cerium.
AB  - We determined the optical properties of alpha- and gamma-phase Ce in the photon
      energy range from 60 meV to 2.5 eV using ellipsometry and grazing incidence
      reflectometry. We observe significant changes of the optical conductivity, the
      dynamical scattering rate, and the effective mass between alpha- and gamma
      cerium. The alpha-phase is characterized by a Fermi-liquid frequency-dependent
      scattering rate, and an effective mass of about 20m(e) on an energy scale of
      about 0.2 eV. In gamma-Ce the charge carriers have a large scattering rate in the
      far infrared and a carrier mass characteristic of 5d band electrons. In addition,
      we observe a prominent absorption feature in alpha-Ce, which is absent in gamma
      Ce.

PMID- 11327983
TI  - Standing optical phonons in finite semiconductor superlattices studied by
      resonant Raman scattering in a double microcavity.
AB  - We report optical double resonant enhancement of Raman scattering in a new double
      microcavity geometry. The design allows almost backscattering geometries,
      providing easy access to the excitations' in-plane dispersion. The cavity is used
      to study the phonon spectra of a finite GaAs/AlAs superlattice. A new type of
      "standing optical vibration" is demonstrated involving the GaAs confined phonons
      with a standing wave envelope determined by the superlattice thickness. A strong
      dispersion of the first order standing wave mode is observed, as well as its
      anticrossing with higher order confined modes of the same symmetry.

PMID- 11327984
TI  - X-ray magneto-optics in lanthanides.
AB  - Magneto-optical methods in the visible light regime generally lack element
      specificity, which has become a considerable shortcoming in research on advanced
      heteromagnetic systems. Using circularly polarized soft x rays tuned to a 4d-4f
      core-level transition of a lanthanide element, the specularly reflected x-ray
      intensity changes proportionally to the magnetization of this element and, e.g.,
      hystereses are easily measured element specifically. In contrast to the case of
      visible light, temperature dependent 4d-4f magneto-optical signals are not
      influenced by the thermal lattice expansion.

PMID- 11327985
TI  - Magnetic moments at the surface of antiferromagnetic NiO(100).
AB  - The orientation of magnetic moments at the (100) surface of antiferromagnetic NiO
      single crystals is studied by x-ray linear magnetic dichroism in photoemission
      microscopy. T domains are observed terminating at the surface, with domain
      boundaries running mostly along in-plane [10] directions. From the detailed
      polarization dependence we find that the magnetic surface structure of a cleaved
      crystal is bulk terminated. This is in contrast to sputtered surfaces, where
      magnetic moments lie within the surface plane, forming a magnetically relaxed
      structure. These findings are of importance for understanding the exchange bias
      phenomenon.

PMID- 11327986
TI  - Reverse Brazil nut problem: competition between percolation and condensation.
AB  - In the Brazil nut problem (BNP), hard spheres with larger diameters rise to the
      top. There are various explanations (percolation, reorganization, convection),
      but a broad understanding or control of this effect is by no means achieved. A
      theory is presented for the crossover from BNP to the reverse Brazil nut problem
      based on a competition between the percolation effect and the condensation of
      hard spheres. The crossover condition is determined, and theoretical predictions
      are compared to molecular dynamics simulations in two and three dimensions.

PMID- 11327987
TI  - Experimental evidence for a kinetic transition in reversible reactions.
AB  - We provide a first experimental verification of a theoretical prediction of a
      kinetic transition in a reversible binding reaction, AB right harpoon over left
      harpoon A+B, driven by the difference in effective lifetimes of the bound and the
      unbound states. We consider the kinetics of excited-state proton transfer to
      solvent from a photoacid whose conjugate anionic base possesses an extremely
      short unbound anion lifetime. Its solvent variation relative to the overall
      dissociation rate coefficient induces a transition in the kinetics, from power
      law to exponential.

PMID- 11327988
TI  - Spiking behavior in a noise-driven system combining oscillatory and excitatory
      properties.
AB  - We show that firing activity (spiking) can be regularized by noise in a FitzHugh
      Nagumo (FHN) neuron model when operating slightly beyond the supercritical Hopf
      bifurcation (in the "canard" region). We also provide the conditions for
      imperfect phase locking between interspike intervals and low amplitude
      quasiharmonic oscillations. For the imperfect phase locking no need exists of an
      external signal as it follows from the FHN intrinsic dynamics.

PMID- 11327989
TI  - Voltage-driven DNA translocations through a nanopore.
AB  - We measure current blockade and time distributions for single-stranded DNA
      polymers during voltage-driven translocations through a single alpha-hemolysin
      pore. We use these data to determine the velocity of the polymers in the pore.
      Our measurements imply that, while polymers longer than the pore are translocated
      at a constant speed, the velocity of shorter polymers increases with decreasing
      length. This velocity is nonlinear with the applied field. Based on this data, we
      estimate the effective diffusion coefficient and the energy penalty for extending
      a molecule into the pore.

PMID- 11327991
TI  - Stochastic biperiodic oscillations in the electroreceptors of paddlefish.
AB  - We report that the electroreceptors in paddlefish possess the novel property of
      being biperiodic, that is, being composed of two intrinsic self-sustained noisy
      oscillators, one residing in the hair cells, and another in the terminals of
      primary afferent neurons. The two oscillators are coupled unidirectionally. Thus
      the receptor system as a whole undergoes stochastic biperiodic oscillations. We
      characterize the spontaneous activity of this system of coupled biological
      oscillators, and also discuss the impact of the biperiodic organization on the
      transduction of external sensory stimuli. In particular, we show that the
      existence of hair cell oscillations leads to additional variability of afferent
      spike trains.

PMID- 11327990
TI  - Coherent dynamics of photoexcited green fluorescent proteins.
AB  - The coherent dynamics of vibronic wave packets in the green fluorescent protein
      is reported. At room temperature the nonstationary dynamics following impulsive
      photoexcitation displays an oscillating optical transmissivity pattern with
      components at 67 fs (497 cm(-1)) and 59 fs (593 cm(-1)). Our results are
      complemented by ab initio calculations of the vibrational spectrum of the
      chromophore. This analysis shows the interplay between the dynamics of the
      aminoacidic structure and the electronic excitation in the primary optical events
      of green fluorescent proteins.

PMID- 11327993
TI  - Anisotropy of the superconducting order parameter in kappa-(BEDT-TTF)2Cu(NCS)(2).

PMID- 11327992
TI  - Observation of equipartition of seismic waves.
AB  - Equipartition is a first principle in wave transport, based on the tendency of
      multiple scattering to homogenize phase space. We report observations of this
      principle for seismic waves created by earthquakes in Mexico. We find qualitative
      agreement with an equipartition model that accounts for mode conversions at the
      Earth's surface.

PMID- 11327994
TI  - Comment on "Millimeter-wave magneto-optical determination of the anisotropy of
      the superconducting order parameter in the molecular superconductor kappa-(BEDT
      TTF)2Cu(NCS)(2)".

PMID- 11327996
TI  - Comment on "Stripe glasses: Self-generated randomness in a uniformly frustrated
      system".

PMID- 11327998
TI  - Bose-Einstein condensation of metastable helium.
AB  - We have observed a Bose-Einstein condensate in a dilute gas of 4He in the
      (3)2S(1) metastable state. We find a critical temperature of (4.7+/-0.5) microK
      and a typical number of atoms at the threshold of 8 x 10(6). The maximum number
      of atoms in our condensate is about 5 x 10(5). An approximate value for the
      scattering length a = (16+/-8) nm is measured. The mean elastic collision rate at
      threshold is then estimated to be about 2 x 10(4) s(-1), indicating that we are
      deeply in the hydrodynamic regime. The typical decay time of the condensate is 2
      s, which places an upper bound on the rate constants for two-body and three-body
      inelastic collisions.

PMID- 11327999
TI  - Steady-state thermodynamics of Langevin systems.
AB  - We study Langevin dynamics describing nonequilibirum steady states. Employing the
      phenomenological framework of steady-state thermodynamics constructed by Oono and
      Paniconi [Prog. Theor. Phys. Suppl. 130, 29 (1998)], we find that the extended
      form of the second law which they proposed holds for transitions between steady
      states and that the Shannon entropy difference is related to the excess heat
      produced in an infinitely slow operation. A generalized version of the Jarzynski
      work relation plays an important role in our theory.

PMID- 11328000
TI  - Unitarity bounds and the cuspy halo problem.
AB  - Conventional cold dark matter cosmological models predict cuspy halos which are
      in apparent conflict with observations. We show that unitarity arguments imply
      interesting constraints on two proposals to address this problem: collisional
      dark matter and strongly annihilating dark matter. Efficient scattering in both
      implies m less, similar to 12 GeV and m less, similar to 25 GeV, respectively. We
      also show that the strong annihilation in the second scenario implies the
      presence of elastic scattering. Recent evidence suggests a collisional scenario
      where the cross section scales inversely with velocity--we argue superelastic
      processes are likely involved. Exceptions and implications for searches are
      discussed.

PMID- 11328001
TI  - End point of the rp process on accreting neutron stars.
AB  - We calculate the rapid proton ( rp) capture process of hydrogen burning on the
      surface of an accreting neutron star with an updated reaction network that
      extends up to Xe, far beyond previous work. In both steady-state nuclear burning
      appropriate for rapidly accreting neutron stars (such as the magnetic polar caps
      of accreting x-ray pulsars) and unstable burning of type I x-ray bursts, we find
      that the rp process ends in a closed SnSbTe cycle. This prevents the synthesis of
      elements heavier than Te and has important consequences for x-ray burst profiles,
      the composition of accreting neutron stars, and potentially galactic
      nucleosynthesis of light p nuclei.

PMID- 11328003
TI  - Supersymmetry and the anomalous anomalous magnetic moment of the muon.
AB  - The recently reported measurement of the muon's anomalous magnetic moment differs
      from the standard model prediction by 2.6 sigma. We examine the implications of
      this discrepancy for supersymmetry. Deviations of the reported magnitude are
      generic in supersymmetric theories. Based on the new result, we derive model
      independent upper bounds on the masses of observable supersymmetric particles. We
      also examine several model frameworks. The sign of the reported deviation is as
      predicted in many simple models, but disfavors anomaly-mediated supersymmetry
      breaking.

PMID- 11328002
TI  - Cosmology from MAXIMA-1, BOOMERANG, and COBE DMR cosmic microwave background
      observations.
AB  - Recent results from BOOMERANG-98 and MAXIMA-1, taken together with COBE DMR,
      provide consistent and high signal-to-noise measurements of the cosmic microwave
      background power spectrum at spherical harmonic multipole bands over 2<l less
      similar to 800. Analysis of the combined data yields 68% (95%) confidence limits
      on the total density, Omega(tot) approximately 1.11+/-0.07 (+0.13)(-0.12), the
      baryon density, Omega(b)h(2) approximately 0.032(+0.005)(-0.004) (+0.009)(
      0.008), and the scalar spectral tilt, n(s) approximately 1.01(+0.09)(-0.07)
      (+0.17)(-0.14). These data are consistent with inflationary initial conditions
      for structure formation. Taken together with other cosmological observations,
      they imply the existence of both nonbaryonic dark matter and dark energy in the
      Universe.

PMID- 11328004
TI  - Implications of muon g -- 2 for supersymmetry and for discovering superpartners
      directly.
AB  - We study the implications of interpreting the recent muon g(mu) -- 2 deviation
      from the standard model prediction as evidence for virtual superpartners, with
      very general calculations that include effects of phases and are consistent with
      all relevant constraints. Assuming that the central value is confirmed with
      smaller errors, there are upper limits on masses: at 1.5 sigma, at least one
      superpartner mass is below about 450 GeV (550 GeV) for tan beta = 35 (50) and may
      be produced at the Fermilab Tevatron in the upcoming run.

PMID- 11328005
TI  - Neutrino unification.
AB  - Present neutrino data are consistent with neutrino masses arising from a common
      seed at some "neutrino unification" scale M(X). Such a simple theoretical ansatz
      naturally leads to quasidegenerate neutrinos that could lie in the electron-volt
      range with neutrino mass splittings induced by renormalization effects associated
      with supersymmetric thresholds. In such a scheme the leptonic analog of the
      Cabibbo angle straight theta(middle dot in circle) describing solar neutrino
      oscillations is nearly maximal. Its exact value is correlated with the smallness
      of straight theta(reactor). The two leading mass-eigenstate neutrinos present in
      nu(e) form a pseudo-Dirac neutrino, avoiding conflict with neutrinoless double
      beta decay.

PMID- 11328006
TI  - Enforced electrical neutrality of the color-flavor locked phase.
AB  - We demonstrate that quark matter in the color-flavor locked phase of QCD is
      rigorously electrically neutral, despite the unequal quark masses, and even in
      the presence of an electron chemical potential. As long as the strange quark mass
      and the electron chemical potential do not preclude the color-flavor locked
      phase, quark matter is automatically neutral. No electrons are required and none
      are admitted.

PMID- 11328007
TI  - Energy and centrality dependence of rapidity densities at RHIC energies.
AB  - The energy and centrality dependence of the charged multiplicity per participant
      nucleon is shown to be able to differentiate between final state saturation and
      fixed scale perturbative QCD models of initial entropy production in high-energy
      heavy-ion collisions. The energy dependence is shown to test the nuclear
      enhancement of the minijet component of the initial conditions, while the
      centrality dependence provides a key test of whether gluon saturation is reached
      at RHIC energies. The HIJING model predicts that the rapidity density per
      participant increases with centrality, while the saturation model prediction is
      essentially independent of centrality.

PMID- 11328009
TI  - Self-consistency requirement in high-energy nuclear scattering.
AB  - Practically all serious calculations of exclusive particle production in
      ultrarelativistic nuclear or hadronic interactions are performed in the framework
      of Gribov-Regge theory or the eikonalized parton model scheme. It is the purpose
      of this paper to point out serious inconsistencies in the above-mentioned
      approaches. We demonstrate that requiring theoretical self-consistency reduces
      the freedom in modeling high-energy nuclear scattering enormously, and we
      introduce a fully self-consistent formulation of the multiple-scattering scheme
      in the framework of a Gribov-Regge--type effective theory. In addition, we
      develop new computational techniques which allow for the first time a
      satisfactory solution of the problem in the sense that calculations of observable
      quantities can be done strictly within a self-consistent formalism.

PMID- 11328010
TI  - Measurement of the beta beta-decay rate of 100Mo to the first excited 0(+) State
      of 100Ru.
AB  - The double-beta beta beta(2 nu)-decay rate of 100Mo to the first excited 0(+)
      state of 100Ru has been measured by a gamma-gamma coincidence technique that uses
      two HPGe detectors to observe the two gamma rays ( E(gamma 1) = 590.76 keV;
      E(gamma 2) = 539.53 keV) from the 100Ru nucleus as it deexcites to the ground
      state via the 0(+)-->2(+)-->0(+) sequence. Unlike all previous beta beta-decay
      experiments, this technique provides data which have a large signal-to-background
      ratio. After a 440-day measurement of a 1.05-kg isotopically enriched (98.4%)
      disk of 100Mo, 22 detected coincidence events (with an estimated background of
      2.5 events) yield a half-life of [5.9(+1.7)(-1.1)(stat)+/-0.6(syst)] x 10(20)
      years.

PMID- 11328011
TI  - Universal fluctuations in heavy-ion collisions in the Fermi energy domain.
AB  - We discuss the scaling laws of both the charged fragments multiplicity n
      fluctuations and the charge of the largest fragment Z(max) fluctuations for Xe +
      Sn collisions in the range of bombarding energies between 25A MeV and 50A MeV. We
      show at E(lab) > or similar to 32 MeV/A the transition in the fluctuation regime
      of Z(max) which is compatible with the transition from the ordered to disordered
      phase of excited nuclear matter. The size (charge) of the largest fragment is
      closely related to the order parameter characterizing this process.

PMID- 11328012
TI  - Random scattering by atomic density fluctuations in optical lattices.
AB  - We investigate hitherto unexplored regimes of probe scattering by atoms trapped
      in optical lattices: weak scattering by effectively random atomic density
      distributions and multiple scattering by arbitrary atomic distributions. Both
      regimes are predicted to exhibit a universal semicircular scattering line shape
      for large density fluctuations, which depend on temperature and quantum
      statistics.

PMID- 11328013
TI  - Few cycle dynamics of multiphoton double ionization.
AB  - In intense field ionization, an electron removed from the atomic core oscillates
      in the combined fields of the laser and the parent ion. This oscillation forces
      repeated revivals of its spatial correlation with the bound electrons. The total
      probability of double ionization depends on the number of returns and therefore
      on the number of optical periods in the laser pulse. We observed the yield of
      Ne(2+) relative to Ne(+) with 12 fs pulses to be clearly less compared to 50 fs
      pulses in qualitative agreement with our theoretical model.

PMID- 11328014
TI  - Observation of accurate ion dissociation thresholds in pulsed field ionization
      photoelectron studies.
AB  - We report the first observation, together with a mechanism for such an
      observation, of a steplike feature in the pulsed field ionization photoelectron
      measurement of CH4(C2H2), marking the 0 K dissociation threshold for the
      formation of CH3(+) + H(C2H(+) + H) from CH4(C2H2). The nonexistence of a step in
      the spectrum for C 2H4 at its dissociation threshold for C2H2(+) formation
      provides strong support for the proposed mechanism. This experiment shows that,
      for a range of molecules, where the ion dissociation lifetimes near the
      dissociation thresholds are <10(-7) s, pulsed field ionization photoelectron
      measurements will yield not only highly accurate ionization energies, but also 0
      K dissociation thresholds.

PMID- 11328015
TI  - Kinetically assisted potential sputtering of insulators by highly charged ions.
AB  - A new form of potential sputtering has been found for impact of slow ( < or =
      1500 eV) multiply charged Xe ions (charge states up to q = 25) on MgO(x). In
      contrast to alkali-halide or SiO2 surfaces this mechanism requires the
      simultaneous presence of electronic excitation of the target material and of a
      kinetically formed collision cascade within the target in order to initiate the
      sputtering process. This kinetically assisted potential sputtering mechanism has
      been identified to be present for other insulating surfaces as well.

PMID- 11328016
TI  - Generation of photon number states on demand via cavity quantum electrodynamics.
AB  - Many applications in quantum information or quantum computing require radiation
      with a fixed number of photons. This increased the demand for systems able to
      produce such fields. We discuss the production of photon fields with a fixed
      photon number on demand. The first experimental demonstration of the device is
      described. This setup is based on a cavity quantum electrodynamics scheme using
      the strong coupling between excited atoms and a single-mode cavity field.

PMID- 11328008
TI  - Centrality dependence of charged particle multiplicity in Au-Au collisions at
      square root of (s)NN = 130 GeV.
AB  - We present results for the charged-particle multiplicity distribution at
      midrapidity in Au-Au collisions at square root of [s(NN)] = 130 GeV measured with
      the PHENIX detector at RHIC. For the 5% most central collisions we find dN(ch)/d
      eta(vertical line eta = 0) = 622+/-1(stat)+/-41(syst). The results, analyzed as a
      function of centrality, show a steady rise of the particle density per
      participating nucleon with centrality.

PMID- 11328017
TI  - Chaotic ionization of nonhydrogenic alkali Rydberg states.
AB  - We report the first ab initio quantum treatment of microwave driven alkali
      Rydberg states. We find that nonhydrogenic atomic initial states exhibit
      fingerprints of classically chaotic excitation, and identify the cause of their
      experimentally observed enhanced ionization, as compared to Rydberg states of
      atomic hydrogen.

PMID- 11328018
TI  - Synchronization of single-side locally averaged adaptive coupling and its
      application to shock capturing.
AB  - We propose a single-sided locally averaged adaptive coupling scheme for the
      synchronization of spatially extended systems. Coupling and synchronization are
      analyzed from the viewpoint of image filter construction and numerical
      dissipation. Single-sided locally averaged coupling is introduced based on the
      resolution argument of control process. Control sensors are adaptively selected
      and automatically adjusted according to the magnitude of local oscillations. We
      demonstrate that the present scheme can effectively suppress and control
      spatiotemporal oscillations and, thus, provide a powerful approach for shock
      capturing. Both the Navier-Stokes equation and Burgers' equation are used to
      illustrate the idea.

PMID- 11328019
TI  - Superluminal to subluminal transition in the pulse propagation in a resonantly
      absorbing medium.
AB  - We have examined the propagation of femtosecond laser pulses in an absorbing dye
      solution through a short to a long range of propagation distance. The transmitted
      pulses show strong spectral shift and a superluminal to subluminal transition in
      the propagation velocity keeping its initial shape almost intact. It is verified
      that the peak velocity is well described by a modified group velocity v(S)
      defined within the framework of the saddle-point method as well as by a recent
      prediction of the net group delay of surviving frequency.

PMID- 11328020
TI  - Photoacoustic point source.
AB  - We investigate the photoacoustic effect generated by heat deposition at a point
      in space in an inviscid fluid. Delta-function and long Gaussian optical pulses
      are used as sources in the wave equation for the displacement potential to
      determine the fluid motion. The linear sound-generation mechanism gives bipolar
      photoacoustic waves, whereas the nonlinear mechanism produces asymmetric tripolar
      waves. The salient features of the photoacoustic point source are that rapid heat
      deposition and nonlinear thermal expansion dominate the production of ultrasound.

PMID- 11328021
TI  - Heat conduction in a one-dimensional gas of elastically colliding particles of
      unequal masses.
AB  - We study the nonequilibrium state of heat conduction in a one-dimensional system
      of hard point particles of unequal masses interacting through elastic collisions.
      A BBGKY-type formulation is presented and some exact results are obtained from
      it. Extensive numerical simulations for the two-mass problem indicate that, even
      for arbitrarily small mass differences, a nontrivial steady state is obtained.
      This state exhibits local thermal equilibrium and has a temperature profile as
      predicted by kinetic theory. The temperature jumps typically seen in such studies
      are shown to be finite-size effects. The thermal conductivity appears to have a
      very slow divergence with system size, different from that seen in most other
      systems.

PMID- 11328022
TI  - Inhibition of the finite-time singularity during droplet fission of a polymeric
      fluid.
AB  - When a drop of fluid detaches from a capillary, singular behavior ensues. We show
      that the addition of very small amounts of polymer inhibits this singularity in
      an abrupt way and gives rise, after a period of self-similar dynamics as for
      simple liquids, to long-lived cylindrical necks or filaments which thin
      exponentially in time. This abrupt change occurs when the elongation rate
      epsilon* becomes comparable to the inverse of the polymer relaxation time leading
      to a large elongational viscosity eta(E) of the dilute polymer solution.

PMID- 11328023
TI  - Three-dimensional simulations of ion acceleration from a foil irradiated by a
      short-pulse laser.
AB  - Using 3D particle-in-cell simulations we study ion acceleration from a foil
      irradiated by a laser pulse at 10(19) W/cm(2) intensity. At the front side, the
      laser ponderomotive force pushes electrons inwards, thus creating the electric
      field by charge separation, which drags the ions. At the back side of the foil,
      the ions are accelerated by space charge of the hot electrons exiting into
      vacuum, as suggested by Hatchett et al. [Phys. Plasmas 7, 2076 (2000)]. The
      transport of hot electrons through the overdense plasma and their exit into
      vacuum are strongly affected by self-generated magnetic fields. The fast ions
      emerge from the rear surface in cones similar to those detected by Clark et al.
      [Phys. Rev. Lett. 84, 670 (2000)].

PMID- 11328024
TI  - Co dimers observed by extended x-ray absorption fine structure spectroscopy.
AB  - Cobalt was introduced into a silver matrix by ion implantation and observed by
      extended x-ray absorption fine structure (EXAFS) spectroscopy. In the range 0.10-
      0.70 at. % evidence of Co dimers dispersed in the matrix was found. The dimers
      are somewhat contracted with respect to the bulk Co nearest neighbor distance and
      distributed in a chainlike configuration with each dimer at 90 degrees from each
      other along opposite square faces of the Ag fcc lattice.

PMID- 11328025
TI  - Entropic effects on the size dependence of cluster structure.
AB  - We show that the vibrational entropy can play a crucial role in determining the
      equilibrium structure of clusters by constructing structural phase diagrams
      showing how the structure depends upon both size and temperature. These phase
      diagrams are obtained for example rare gas and metal clusters.

PMID- 11328026
TI  - Atomic and electronic structures of N-incorporated Si oxides.
AB  - We present first-principles total-energy calculations on the N-incorporated Si
      oxides, regarded as a replacement for conventional SiO2 in device technology. We
      investigate the energetics, charge states, and electronic structures for various
      bond configurations around N. While they remain in the N-incorporated structures,
      the charge trap states, responsible for leakage current in SiO2, are effectively
      removed from the energy gap in the H-terminated structures. This shows that
      improvement in the electrical reliabilities of Si oxynitride films is originated
      not from N incorporation itself, but from the coexistence of N and H.

PMID- 11328027
TI  - Lattice Boltzmann model for anisotropic liquid-solid phase transition.
AB  - We develop a simple reaction model for the liquid-solid phase transition in the
      context of the lattice Boltzmann method with enhanced collisions. Calculations
      for a two-dimensional test problem of Ga melting and for a two-dimensional
      anisotropic growth of dendrites are presented and commented on.

PMID- 11328028
TI  - Exactly solvable toy model that mimics the mode coupling theory of supercooled
      liquid and glass transition.
AB  - A toy model is proposed which incorporates the reversible mode coupling mechanism
      responsible for ergodic-nonergodic transition of the mode coupling theory (MCT)
      of structural glass transition with trivial Hamiltonian. The model can be
      analyzed without relying on uncontrolled approximations inevitable in the current
      MCT. The strength of hopping processes can be easily tuned and the ideal glass
      transition is reproduced only in a certain range of the strength. On the basis of
      the analyses of our model, we discuss about a sharp ergodic-nonergodic transition
      and its smearing out by "hopping."

PMID- 11328029
TI  - Subsurface dimerization in III-V semiconductor (001) surfaces.
AB  - We present the atomic structure of the c(8 x 2) reconstructions of InSb-, InAs-,
      and GaAs-(001) surfaces as determined by surface x-ray diffraction using direct
      methods. Contrary to common belief, group III dimers are not prominent on the
      surface, instead subsurface dimerization of group III atoms takes place in the
      second bilayer, accompanied by a major rearrangement of the surface atoms above
      the dimers to form linear arrays. By varying the occupancies of four surface
      sites the (001)-c(8 x 2) reconstructions of III-V semiconductors can be described
      in a unified model.

PMID- 11328030
TI  - Decorated Ag19 on Pt(111) or the "rare gas necklace".
AB  - Ag19 cluster ions are mass selected and deposited on a Pt(111) surface covered by
      five monolayers of Kr. Almost monodispersed hexagonal shaped Ag islands are
      observed after Kr evaporation at 125 K. The identification of the island shape
      and the exact number of atoms has been successful by decorating the clusters with
      Kr atoms which can be counted by high resolution scanning tunneling microscopy.

PMID- 11328031
TI  - Reconciling conductance fluctuations and the scaling theory of localization.
AB  - We reconcile the phenomenon of mesoscopic conductance fluctuations with the
      single parameter scaling theory of the Anderson transition. We calculate three
      averages of the conductance distribution, exp(<lng>), <g>, and 1/<R>, where g is
      the conductance in units of e(2)/h and R = 1/g is the resistance, and demonstrate
      that these quantities obey single parameter scaling laws. We obtain consistent
      estimates of the critical exponent from the scaling of all these quantities.

PMID- 11328032
TI  - Effect of anisotropic strain on the crosshatch electrical activity in relaxed
      GeSi films.
AB  - The physical origin of the crosshatch electrical activity in relaxed GeSi films
      was studied using a near-field scanning optical microscope (NSOM). The contrast
      and patterns in the near-field photocurrent images depend on the polarization
      direction of the NSOM light. These results rule out composition nonuniformity,
      junction depth variation, and scanning artifacts as dominant sources of the
      contrast. Numerical calculations show that local changes in band structure due to
      strain fields of the misfit dislocations are responsible for the experimental
      observations.

PMID- 11328033
TI  - Polaron dynamics in a system of coupled conjugated polymer chains.
AB  - The motion of excitations such as polarons is believed to be of fundamental
      importance for the transport properties of conjugated polymers for the use in,
      e.g., polymer based LED's. We have investigated polaron dynamics in a system of
      coupled polymer chains in the presence of an external electric field. In
      particular, we focus on how a polaron migrates through the polymer lattice, i.e.,
      the situation in which a polaron reaches a chain end and is scattered to the
      surrounding chains. We show that the outcome of this event strongly depends on
      the strength of the electric field, and we identify three different cases for the
      polaron migration.

PMID- 11328034
TI  - Current-induced embrittlement of atomic wires.
AB  - Recent experiments suggest that gold single-atom contacts and atomic chains break
      at applied voltages of 1 to 2 V. In order to understand why current flow affects
      these defect-free conductors, we have calculated the current-induced forces on
      atoms in a Au chain between two Au electrodes. These forces are not by themselves
      sufficient to rupture the chain. However, the current reduces the work to break
      the chain, which results in a dramatic increase in the probability of thermally
      activated spontaneous fracture of the chain. This current-induced embrittlement
      poses a fundamental limit to the current-carrying capacity of atomic wires.

PMID- 11328035
TI  - Mesoscopic fluctuations of the Coulomb drag at nu = 1/2.
AB  - We consider mesoscopic fluctuations of Coulomb drag transresistivity between two
      layers at a Landau level filling factor nu = 1/2 each. We find that, at low
      temperatures, sample to sample fluctuations exceed both the ensemble average and
      the corresponding fluctuations at B = 0. At the experimentally relevant
      temperatures, the variance of the transresistivity is proportional to T(-1/2). We
      find the dependence of this variance on density and magnetic field to reflect the
      attachment of two flux quanta to each electron.

PMID- 11328036
TI  - New class of magnetoresistance oscillations: interaction of a two-dimensional
      electron gas with leaky interface phonons.
AB  - We report on a new class of magnetoresistance oscillations observed in a high
      mobility two-dimensional electron gas (2DEG) in GaAs-Al(x)Ga(1--x)As
      heterostructures. Appearing in a weak magnetic field ( B < 0.3 T) and only in a
      narrow temperature range ( 2 K < T < 9 K), these oscillations are periodic in 1/B
      with a frequency proportional to the electron Fermi wave vector, k(F). We
      interpret the effect as a magnetophonon resonance of the 2DEG with leaky
      interface-acoustic phonon modes carrying a wave vector q = 2k(F). Calculations
      show a few branches of such modes existing on the GaAs-Al(x)Ga(1--)xAs interface,
      and their velocities are in quantitative agreement with the observation.

PMID- 11328037
TI  - Precision calculation of magnetization and specific heat of vortex liquids and
      solids in type-II superconductors.
AB  - A new systematic calculation of magnetization and specific heat contributions of
      vortex liquids and solids is presented. We develop an optimized perturbation
      theory for the Ginzburg-Landau description of thermal fluctuations effects in the
      vortex liquids. The expansion is convergent in contrast to the conventional high
      temperature expansion which is asymptotic. In the solid phase we calculate the
      first two orders which are already quite accurate. The results are in good
      agreement with existing Monte Carlo simulations and experiments. Limitations of
      various nonperturbative and phenomenological approaches are noted. In particular,
      we show that there is no exact intersection point of the magnetization curves.

PMID- 11328038
TI  - Flux front penetration in disordered superconductors.
AB  - We investigate flux front penetration in a disordered type-II superconductor by
      molecular dynamics simulations of interacting vortices and find scaling laws for
      the front position and the density profile. The scaling can be understood by
      performing a coarse graining of the system and writing a disordered nonlinear
      diffusion equation. Integrating numerically the equation, we observe a crossover
      from flat to fractal front penetration as the system parameters are varied. The
      value of the fractal dimension indicates that the invasion process is described
      by gradient percolation.

PMID- 11328039
TI  - New vortex-matter size effect observed in Bi(2)Sr(2)CaCu(2)O(8 + delta).
AB  - The vortex-matter 3D to 2D phase transition is studied in micron-sized
      Bi(2)Sr(2)CaCu(2)O(8 + delta) single crystals using local Hall magnetization
      measurements. At a given temperature, the second magnetization peak, the
      signature of a possible 3D--2D vortex phase transition, disappears for samples
      smaller than a critical length. We suggest that this critical length should be
      equated with the 2D vortex lattice ab-plane correlation length R(2D)(c). The
      magnitude and temperature dependence of R(2D)(c) agree well with Larkin
      Ovchinnikov collective pinning theory.

PMID- 11328040
TI  - Collective pinning of a frozen vortex liquid in ultrathin superconducting
      YBa2Cu3O7 films.
AB  - The linear dynamic response of the two-dimensional (2D) vortex medium in
      ultrathin YBa2Cu3O7 films was studied by measuring their ac sheet impedance Z
      over a broad range of frequencies omega. With decreasing temperature the
      dissipative component of Z exhibits, at a temperature T*(omega) well above the
      melting temperature of a 2D vortex crystal, a crossover from a thermally
      activated regime involving single vortices to a regime where the response has
      features consistent with a description in terms of a collectively pinned vortex
      manifold. This suggests the idea of a vortex liquid which, below T*(omega),
      appears to be frozen at the time scales 1/omega of the experiments.

PMID- 11328041
TI  - Non-Stoner continuum in the double exchange model.
AB  - Exact diagonalization studies of the double exchange model indicate the existence
      of continuum states in the single-spin-flip channel that overlap the magnons at
      very low energies (approximately 10(-2) eV) and extend to high energies
      (approximately eV). This picture differs dramatically from the prevalent view,
      where there are the magnons, plus the Stoner continuum at the high-energy scale,
      with nothing in between. The relevance of these new continuum states to inelastic
      neutron scattering and optical properties is discussed.

PMID- 11328042
TI  - Orbital frustration at the origin of the magnetic behavior in LiNiO2.
AB  - We report on the ESR, magnetization, and magnetic susceptibility measurements
      performed over a large temperature range, from 1.5 to 750 K, on high-quality
      stoichiometric LiNiO2. We find that this compound displays two distinct
      temperature regions where its magnetic behavior is anomalous. With the help of a
      statistical model based on the Kugel'-Khomskii Hamiltonian, we show that below
      T(of) approximately 400 K, an orbitally frustrated state characteristic of the
      triangular lattice is established. This then gives a solution to the long
      standing controversial problem of the magnetic behavior in LiNiO2.

PMID- 11328043
TI  - Phase transitions, stability, and dielectric response of the domain structure in
      ferroelectric-ferroelastic thin films.
AB  - The first analytical study of phase transitions and domain structure in
      ferroelastic-ferroelectric epitaxial thin films is presented for an exactly
      solvable model. The emerging domain structure with domains of equal width (which
      may be exponentially large) remains stable irrespective of the film thickness.
      Shifts of the domain walls, unexpectedly, contribute nothing (or insignificantly)
      to the dielectric response of the film. Generally, the motion of the domain walls
      results in about the same contribution to the response as the one that comes from
      a standard bulk term. Therefore, no particular softening of the dielectric
      response is expected to occur due to the motion of domain walls.

PMID- 11328044
TI  - Element-selective nanosecond magnetization dynamics in magnetic heterostructures.
AB  - We have developed a new original technique to study the magnetization reversal
      dynamics of thin films with element selectivity in the nanosecond time scale. X
      ray magnetic circular dichroism measurements in pump-probe mode are carried out
      taking advantage of the time structure of synchrotron radiation. The dynamics of
      the magnetization reversal of each of the layers of complex heterostructures
      (like spin valves or tunnel junctions) can be probed independently. The
      interlayer coupling in the studied systems has been shown to play a key role in
      the determination of the magnetization reversal of each individual layer.

PMID- 11328045
TI  - Ultrafast laser-induced phase transitions in amorphous GeSb films.
AB  - Time-resolved measurements of the spectral dielectric function reveal new
      information about ultrafast phase transitions induced by femtosecond laser pulses
      in Sb-rich amorphous GeSb films. The excitation generates a nonthermal phase
      within 200 fs. The dielectric function of this phase differs from that of the
      crystalline phase, contrary to previous suggestions of a disorder-to-order
      transition. The observed dielectric function is close to that of the liquid
      phase, indicating an ultrafast transition from the amorphous phase to a different
      disordered state.

PMID- 11328046
TI  - Spin polarized metastable He*(2(3)S, 1s2s) stimulated desorption of H(+) ions.
AB  - The yield of H(+) in the metastable He*(2(3)S, 1s2s) stimulated desorption (MSD)
      on an H2O/Na/Fe surface has been found to depend on the spin of the incident He*.
      By combination with the spin-resolved analysis for the surface electronic
      structure, it is indicated that the neutralization of the hole in the OH 3 sigma
      molecular orbital, which is created by the incident He*, by Na 3s electrons plays
      a crucial role in the spin polarization of the H (+) MSD intensity. The
      dependence of the spin polarization of H(+) MSD on the kinetic energy of the
      desorbed H(+) has been observed, and it is discussed based on the Menzel-Gomer
      Readhead model.

PMID- 11328047
TI  - Bound entangled Gaussian states.
AB  - We discuss the entanglement properties of bipartite states with Gaussian Wigner
      functions. For the separability, and the positivity of the partial transpose, we
      establish explicit necessary and sufficient criteria in terms of the covariance
      matrix of the state. It is shown that, for systems composed of a single
      oscillator for Alice and an arbitrary number for Bob, positivity of the partial
      transpose implies separability. However, this implication fails with two
      oscillators on each side, as we show by constructing a five parameter family of
      bound entangled Gaussian states.

PMID- 11328048
TI  - Correlation detection and resonance in neural systems with distributed noise
      sources.
AB  - We investigated the resonance behavior in model neurons receiving a large number
      of random synaptic inputs, whose distributed nature permits one to introduce
      correlations between them and investigate its effect on cellular responsiveness.
      A change in the strength of this background led to enhanced responsiveness,
      consistent with stochastic resonance. Altering the correlation revealed a type of
      resonance behavior in which the neuron is sensitive to statistical properties
      rather than the strength of the noise. Remarkably, the neuron could detect weak
      correlations among the distributed inputs within millisecond time scales.

PMID- 11328049
TI  - Sequence recognition in the pairing of DNA duplexes.
AB  - Pairing of DNA fragments with homologous sequences occurs in gene shuffling, DNA
      repair, and other vital processes. While chemical individuality of base pairs is
      hidden inside the double helix, x ray and NMR revealed sequence-dependent
      modulation of the structure of DNA backbone. Here we show that the resulting
      modulation of the DNA surface charge pattern enables duplexes longer than
      approximately 50 base pairs to recognize sequence homology electrostatically at a
      distance of up to several water layers. This may explain the local recognition
      observed in pairing of homologous chromosomes and the observed length dependence
      of homologous recombination.

PMID- 11328050
TI  - Metallic conduction through engineered DNA: DNA nanoelectronic building blocks.
AB  - A novel way of engineering DNA molecules involves substituting the imino proton
      of each base pair with a metal ion to obtain M-DNA with altered electronic
      properties. We report the first direct evidence of metalliclike conduction
      through 15 microm long M-DNA. In contrast, measurements on B-DNA give evidence of
      semiconducting behavior with a few hundred meV band gap at room temperature. The
      drastic change of M-DNA conductivity points to a new degree of freedom in the
      development of future molecular electronics utilizing DNA, such as creating all
      DNA junction devices for use as nanoelectronic building blocks.

PMID- 11328051
TI  - Optimal wiring principle and plateaus in the degree of separation for cortical
      neurons.
AB  - Scaling properties of a cortical network wired in a stochastic manner with a
      distance-dependent probability of a direct connection are considered. In the
      infinite network limit, an average degree of separation between neurons displays
      both universality and criticality. The latter feature manifests itself by
      appearance of a stairlike structure with numerous plateaus as a function of a
      connectivity exponent. It is suggested that these plateaus may be advantageous in
      the cortex design. Wiring principle incorporating minimization of both axonal
      length and the degree of separation is also discussed. This principle leads
      naturally to a trade-off between saving axons and saving energy required in the
      communication.

PMID- 11328052
TI  - Defibrillation via the elimination of spiral turbulence in a model for
      ventricular fibrillation.
AB  - Ventricular fibrillation, the major reason behind sudden cardiac death, is
      turbulent cardiac electrical activity in which rapid, irregular disturbances in
      the spatiotemporal electrical activation of the heart make it incapable of any
      concerted pumping action. Methods of controlling ventricular fibrillation include
      electrical defibrillation as well as injected medication. Electrical
      defibrillation, though widely used, involves subjecting the whole heart to
      massive, and often counterproductive, electrical shocks. We propose a
      defibrillation method that uses a very low-amplitude shock (of order mV) applied
      for a brief duration (of order 100 ms) and over a coarse mesh of lines on our
      model ventricle.

PMID- 11328053
TI  - Breakdown of the internet under intentional attack.
AB  - We study the tolerance of random networks to intentional attack, whereby a
      fraction p of the most connected sites is removed. We focus on scale-free
      networks, having connectivity distribution P(k) approximately k(-alpha), and use
      percolation theory to study analytically and numerically the critical fraction
      p(c) needed for the disintegration of the network, as well as the size of the
      largest connected cluster. We find that even networks with alpha < or = 3, known
      to be resilient to random removal of sites, are sensitive to intentional attack.
      We also argue that, near criticality, the average distance between sites in the
      spanning (largest) cluster scales with its mass, M, as square root of [M], rather
      than as log (k)M, as expected for random networks away from criticality.

PMID- 11328054
TI  - Comment on "First observation of ion acoustic waves produced by the Langmuir
      decay instability".

PMID- 11328056
TI  - Comment on "Antilocalization in a 2D electron gas in a random magnetic field".

PMID- 11328058
TI  - Does the 2D Hubbard model really show d-wave superconductivity?

PMID- 11328060
TI  - Comment on "Atomic many-body effects for the p-shell photoelectron spectra of
      transition metals".

PMID- 11328062
TI  - Signal velocity, causality, and quantum noise in superluminal light pulse
      propagation.
AB  - We consider pulse propagation in a linear anomalously dispersive medium where the
      group velocity exceeds the speed of light in vacuum ( c) or even becomes
      negative. A signal velocity is defined operationally based on the optical signal
      to-noise ratio, and is computed for cases appropriate to the recent experiment
      where such a negative group velocity was observed. It is found that quantum
      fluctuations limit the signal velocity to values less than c.

PMID- 11328063
TI  - Spatially selective bragg scattering: a signature for vortices in Bose-Einstein
      condensates.
AB  - We demonstrate that Bragg scattering from a condensate can be sensitive to the
      spatial phase distribution of the initial state. This allows preferential
      scattering from a selected spatial region, and provides a robust signature for a
      vortex state. We develop an analytic model which accurately describes this
      phenomenon, and we give quantitative predictions for current experimental
      conditions.

PMID- 11328064
TI  - Creating vortex rings and three-dimensional skyrmions in Bose-Eeinstein
      condensates.
AB  - We propose a method of generating a vortex ring in a Bose-Einstein condensate by
      means of electromagnetically induced atomic transitions. Some remnant population
      of atoms in a second internal state remains within the toroidal trap formed by
      the mean-field repulsion of the vortex ring. This population can be removed, or
      it can be made to flow around the torus (i.e., within the vortex ring). If this
      flow has a unit topological winding number, the entire structure formed by the
      two condensates is an example of a three-dimensional Skyrmion texture.

PMID- 11328065
TI  - Temperature dependence of damping and frequency shifts of the scissors mode of a
      trapped Bose-Einstein condensate.
AB  - We have studied the properties of the scissors mode of a trapped Bose-Einstein
      condensate of 87Rb atoms at finite temperature. We measured a significant shift
      in the frequency of the mode below the hydrodynamic limit and a strong dependence
      of the damping rate as the temperature increased. We compared our damping rate
      results to recent theoretical calculations for other observed collective modes,
      finding a fair agreement. From the frequency measurements we deduce the moment of
      inertia of the gas and show that it is quenched below the transition point,
      because of the superfluid nature of the condensed gas.

PMID- 11328066
TI  - Noise-activated escape from a sloshing potential well.
AB  - We treat the noise-activated escape from a one-dimensional potential well of an
      overdamped particle, to which a periodic force of fixed frequency is applied.
      Near the well top, the relevant length scales and the boundary layer structure
      are determined. We show how behavior near the well top generalizes the behavior
      determined by Kramers, in the case without forcing. Our analysis includes the
      case when the forcing does not die away in the weak-noise limit. We discuss the
      relevance of scaling regimes, defined by the relative strengths of the forcing
      and the noise, to recent optical trap experiments.

PMID- 11328067
TI  - Upper critical dimension, dynamic exponent, and scaling functions in the mode
      coupling theory for the Kardar-Parisi-Zhang equation.
AB  - We study the mode-coupling approximation for the Kardar-Parisi-Zhang equation in
      the strong-coupling regime. By constructing an ansatz consistent with the
      asymptotic forms of the correlation and response functions we determine the upper
      critical dimension d(c) = 4 and the expansion z = 2-(d-4)/4+O((4-d)2) around dc.
      We find the exact z = 3/2 value in d = 1, and estimate the values z approximately
      1.62, z approximately 1.78 in d = 2, 3. The result dc = 4 and the expansion
      around dc are very robust and can be derived just from a mild assumption on the
      relative scale on which the response and correlation functions vary as z
      approaches 2.

PMID- 11328069
TI  - Domain walls of high-density QCD.
AB  - We show that in very dense quark matter there must exist metastable domain walls
      where the axial U(1) phase of the color-superconducting condensate changes by
      2pi. The decay rate of the domain walls is exponentially suppressed and we
      compute it semiclassically. We give an estimate of the critical chemical
      potential above which our analysis is under theoretical control.

PMID- 11328070
TI  - Towards a test of QED in investigations of the hyperfine splitting in heavy ions.
AB  - A possibility for investigations of quantum electrodynamics (QED) in experiments
      on the hyperfine splitting in heavy ions is examined. It is found that QED
      effects can be probed on the level of a few percent in a specific difference of
      the hyperfine splitting values in hydrogenlike and lithiumlike bismuth. This
      could provide a test of QED in the strongest electric field available at present
      for experimental study.

PMID- 11328068
TI  - Stable operation of a 300-m laser interferometer with sufficient sensitivity to
      detect gravitational-wave events within our galaxy.
AB  - TAMA300, an interferometric gravitational-wave detector with 300-m baseline
      length, has been developed and operated with sufficient sensitivity to detect
      gravitational-wave events within our galaxy and sufficient stability for
      observations; the interferometer was operated for over 10 hours stably and
      continuously. With a strain-equivalent noise level of h approximately 5x10(
      21)/sqrt[Hz], a signal-to-noise ratio of 30 is expected for gravitational waves
      generated by a coalescence of 1.4M-1.4M binary neutron stars at 10 kpc distance.
      We evaluated the stability of the detector sensitivity with a 2-week data-taking
      run, collecting 160 hours of data to be analyzed in the search for gravitational
      waves.

PMID- 11328073
TI  - Implications of the ALEPH tau-lepton decay data for perturbative and
      nonperturbative QCD.
AB  - We use ALEPH data on hadronic tau decays in order to calculate Euclidean
      coordinate space correlation functions in the vector and axial-vector channels.
      The linear combination V-A receives no perturbative contribution and is
      quantitatively reproduced by the instanton liquid model. In the case of V+A the
      instanton calculation is in good agreement with the data once perturbative
      corrections are included. These corrections clearly show the evolution of
      alpha(s). We also analyze the range of validity of the operator product expansion
      (OPE). We conclude that the range of validity of the OPE is limited to x less,
      similar 0.3 fm, whereas the instanton model describes the data over the entire
      range.

PMID- 11328072
TI  - Search for rare and forbidden Charm Meson decays D0 --> Vl+l- and hhll.
AB  - We report results of a search for flavor-changing neutral current (FCNC), lepton
      flavor, and lepton-number violating decays of the D0 (and its antiparticle) into
      three and four bodies. Using data from Fermilab charm hadroproduction experiment
      E791, we examine modes with two leptons (muons or electrons) and a rho(0), K(
      *0), or straight phi vector meson or a nonresonant pi(pi), Kpi, or KK pair of
      pseudoscalar mesons. No evidence for any of these decays is found. Therefore, we
      present branching-fraction upper limits at 90% confidence level for the 27 decay
      modes examined (18 new).

PMID- 11328074
TI  - Observation of exotic meson production in the reaction pi- p --> eta'pi- p at 18
      GeV/c.
AB  - An amplitude analysis of an exclusive sample of 5765 events from the reaction pi-
      p-->eta'pi- p at 18 GeV/c is described. The eta'pi- production is dominated by
      natural parity exchange and by three partial waves: those with J(PC) = 1(-+),
      2(++), and 4(++). A mass-dependent analysis of the partial-wave amplitudes
      indicates the production of the a2(1320) meson as well as the a4(2040) meson,
      observed for the first time decaying to eta'pi-. The dominant, exotic (non- qq)
      1(-+) partial wave is shown to be resonant with a mass of 1.597+/-0.010(+0.045)(
      0.010) GeV/c2 and a width of 0.340+/-0.040+/-0.050 GeV/c2. This exotic state, the
      pi1(1600), is produced with a t dependence which is different from that of the
      a2(1320) meson, indicating differences between the production mechanisms for the
      two states.

PMID- 11328075
TI  - Pion interferometry at RHIC: porobing a thermalized quark-gluon plasma?
AB  - We calculate the Gaussian radius parameters of the pion-emitting source in high
      energy heavy-ion collisions, assuming a first-order phase transition from a
      thermalized quark-gluon plasma (QGP) to a gas of hadrons. Such a model leads to a
      very long-lived dissipative hadronic rescattering phase which dominates the
      properties of the two-pion correlation functions. The radii are found to depend
      only weakly on the thermalization time tau(i), the critical temperature Tc (and
      thus the latent heat), and the specific entropy of the QGP. The model
      calculations suggest a rapid increase of R(out)/R(side) as a function of KT if a
      thermalized QGP were formed.

PMID- 11328076
TI  - Low-energy measurement of the 7Be(p,gamma)8B cross section.
AB  - We have measured the cross section of the 7Be(p,gamma)8B reaction for E(c.m.) =
      185.8, 134.7, and 111.7 keV using a radioactive 7Be target (132 mCi). Single and
      coincidence spectra of beta+ and alpha particles from 8B and 8Be* decay,
      respectively, were measured using a large acceptance spectrometer. The zero
      energy S factor inferred from these data is 18.5+/-2.4 eV b and a weighted mean
      value of 18.8+/-1.7 eV b (theoretical uncertainty included) is deduced when
      combining this value with our previous results at higher energies.

PMID- 11328077
TI  - Solitonic fullerene structures in light atomic nuclei.
AB  - The Skyrme model is a classical field theory which has topological soliton
      solutions. These solitons are candidates for describing nuclei, with an
      identification between the numbers of solitons and nucleons. We have computed
      numerically, using two different minimization algorithms, minimum energy
      configurations for up to 22 solitons. We find, remarkably, that the solutions for
      seven or more solitons have nucleon density isosurfaces in the form of polyhedra
      made of hexagons and pentagons. Precisely these structures arise, though at the
      much larger molecular scale, in the chemistry of carbon shells, where they are
      known as fullerenes.

PMID- 11328078
TI  - High-angular-momentum states in cold Rydberg gases.
AB  - Cold, dense Rydberg gases produced in a cold-atom trap are investigated using
      spectroscopic methods and time-resolved electron counting. Optical excitation on
      the discrete Rydberg resonances reveals long-lasting electron emission from the
      Rydberg gas ( >20 ms). Our observations are explained by lm-mixing collisions
      between Rydberg atoms and slow electrons that lead to the population of long
      lived high-angular-momentum Rydberg states. These atoms thermally ionize slowly
      and with large probabilities.

PMID- 11328079
TI  - Vibrationally inelastic scattering of high- n Rydberg H atoms from N2 and O2.
AB  - The vibrationally inelastic scattering of Rydberg H atoms (n = 30-50) from N2 and
      O2 at E(coll) = 1.84 eV was studied as a function of laboratory deflection angle.
      On average, 4 times more vibrational excitation was observed in collisions with
      O2 than with N2. Vibrational excitation of O2 results largely from collisions in
      which an electron is briefly transferred from O2 to the proton core, while the
      Rydberg electron remains a spectator. This provides further evidence that the
      free electron model applies to low energy collisions involving the ionic core
      leading to substantial momentum transfer.

PMID- 11328080
TI  - Molecular reorientation in collisions of OH + Ar.
AB  - Orientational effects in rotationally elastic collisions of OH with Ar were
      studied in a crossed molecular beam setup. A static electric field was applied to
      orient the molecules before the collision. After the collision the orientation
      was measured by using a narrow-band laser system to probe the Stark-split states
      corresponding to different orientations. Differential and integral cross sections
      for reorientation of the molecular axis have been determined as a function of the
      initial orientation. The cross section for reorientation by one quantum is 25 A2
      with a preference for O-end collisions.

PMID- 11328081
TI  - Rate coefficients and final states for the dissociative recombination of LiH+.
AB  - The dissociative recombination of LiH+ ions with low-energy electrons is observed
      at a storage ring and the final states are analyzed using fragment imaging and
      field ionization techniques. The rate coefficient is found to be larger than its
      estimated value used in astrophysical models. Mostly the highest energetically
      possible Rydberg states of the lithium atom are populated by the reaction,
      indicating a common trend for molecular recombination via the noncrossing mode.

PMID- 11328082
TI  - Experimental observation of spatial antibunching of photons.
AB  - We report an interference experiment that shows transverse spatial antibunching
      of photons. Using collinear parametric down-conversion in a Young-type fourth
      order interference setup, we show interference patterns that violate classical
      Schwarz inequality and should not exist at all in a classical description.

PMID- 11328083
TI  - Entanglement in cascaded-crystal parametric down-conversion.
AB  - We use spontaneous parametric down-conversion in a cascade of crystals, driven by
      a single monochromatic cw pump laser, to study the interference of entangled
      photon pairs. By changing the distance between the crystals, the observed quantum
      interference pattern varies continuously from that associated with a longer
      single crystal to that associated with independent emissions from two distinct
      crystals. Postselection via spectral filtering suppresses this phenomenon. These
      findings are expected to advance the field of quantum-state engineering.

PMID- 11328084
TI  - Experimental observation of superpersistent chaotic transients.
AB  - We present the first experimental observation of superpersistent chaotic
      transients. In particular, we investigate the effect of noise on phase
      synchronization in coupled chaotic electronic circuits and obtain the scaling
      relation that is characteristic of those extremely long chaotic transients.

PMID- 11328085
TI  - Degenerate parametric light scattering in periodically poled LiNbO3:Y:Fe.
AB  - The first observation of parametric light scattering patterns (rings, lines, and
      dots) in bulk periodically poled nonlinear media is reported. Development of the
      scattering patterns proves efficient photorefractive grating recording and
      considerable parametric gain for seed radiation in this new nonlinear material.
      Several novel phase-matched parametric processes, caused by the periodicity of
      the domain structure, are revealed.

PMID- 11328086
TI  - Quantum-noise-induced order in lasers placed in chaotic oscillation by frequency
      shifted feedback.
AB  - A kind of chaotic oscillations featuring random switching between sustained
      relaxation oscillations (RO) and spiking oscillations (SO) has been demonstrated
      in lasers with frequency-shifted feedback. The presence of stochastic frequency
      locking between two periodicities of RO and SO motions and selective quantum
      noise-induced ordering of chaotic spiking oscillations is demonstrated
      theoretically and experimentally.

PMID- 11328087
TI  - Fermi-Pasta-Ulam beta model: boundary jumps, Fourier's law, and scaling.
AB  - We examine the interplay of surface and volume effects in systems undergoing heat
      flow. In particular, we compute the thermal conductivity in the Fermi-Pasta-Ulam
      beta model as a function of temperature and lattice size, and scaling arguments
      are used to provide analytic guidance. From this we show that boundary
      temperature jumps can be quantitatively understood, and that they play an
      important role in determining the dynamics of the system, relating soliton
      dynamics, kinetic theory, and Fourier transport.

PMID- 11328088
TI  - Finite-mode spectral model of homogeneous and isotropic Navier-stokes turbulence:
      a rapidly depleted energy cascade.
AB  - An eddy-viscous term is added to Navier-Stokes dynamics at wave numbers k greater
      than the inflection point kc of the energy flux F(log(k)). The eddy viscosity is
      fixed so that the energy spectrum satisfies E(k) = E(kc) (k/kc)(-3) for k>kc.
      This resulting forcing induces a rapid depletion of the energy cascade at k>kc.
      It is observed numerically that the model reproduces turbulence energetics at k<
      or =kc and statistics of two-point velocity correlations at scales r>lambda
      (Taylor microscale). Compared to a direct numerical simulation of R(lambda) = 130
      an equivalent run with the present model results in a gain of a factor 20 in CPU
      time.

PMID- 11328071
TI  - Production of chi(c1) and chi(c2) in pp collisions at sqrt[S] = 1.8 TeV.
AB  - We have measured the ratio of prompt production rates of the charmonium states
      chi(c1) and chi(c2) in 110 pb(-1) of pp collisions at sqrt[s] = 1.8 TeV. The
      photon from their decay into J/psi(gamma) is reconstructed through conversion
      into e+e- pairs. The energy resolution this technique provides makes the
      resolution of the two states possible. We find the ratio of production cross
      sections sigma(chi(c2))/sigma(chi(c1)) = 0.96+/-0.27(stat)+/-0.11(syst) for
      events with pT(J/psi) > 4.0 GeV/c, /eta(J/psi)/ < 0.6, and pT(gamma) > 1.0 GeV/c.

PMID- 11328089
TI  - Hydrodynamic waves in regions with smooth loss of convexity of isentropes:
      general phenomenological theory.
AB  - A general phenomenological theory of hydrodynamic waves in regions with smooth
      loss of convexity of isentropes is developed, based on the fact that for most
      media these regions in the p-V plane are anomalously small. Accordingly the waves
      are usually weak and can be described in the manner analogous to that for weak
      shock waves of compression. The corresponding generalized Burgers equation is
      derived and analyzed. The exact solution of the equation for steady shock waves
      of rarefaction is obtained and discussed.

PMID- 11328090
TI  - First staging of two laser accelerators.
AB  - Staging of two laser-driven, relativistic electron accelerators has been
      demonstrated for the first time in a proof-of-principle experiment, whereby two
      distinct and serial laser accelerators acted on an electron beam in a coherently
      cumulative manner. Output from a CO2 laser was split into two beams to drive two
      inverse free electron lasers (IFEL) separated by 2.3 m. The first IFEL served to
      bunch the electrons into approximately 3 fs microbunches, which were rephased
      with the laser wave in the second IFEL. This represents a crucial step towards
      the development of practical laser-driven electron accelerators.

PMID- 11328091
TI  - Anomalous viscoelastic response of nematic elastomers.
AB  - We report a combined theoretical and experimental study of linear viscoelastic
      response in oriented monodomain nematic elastomers. The model predicts a dramatic
      decrease in the dynamic modulus in certain deformation geometries in an elastic
      medium with an independently mobile internal degree of freedom, the nematic
      director with its own relaxation dynamics. Dynamic mechanical measurements on
      monodomain nematic elastomers confirm our predictions of dependence on shear
      geometry and on nematic order, and also show a very substantial mechanical loss
      clearly associated with director relaxation.

PMID- 11328092
TI  - Unusual thickness-dependent thermal behavior and anticlinic coupling in chiral
      smectic free-standing liquid-crystal films.
AB  - We observe, in free-standing films of a chiral smectic liquid crystal, a series
      of discrete transitions in the relative orientation of the tilt of the interior
      and surface layers. These transitions include a remarkable reentrant synclinic
      anticlinic-synclinic ordering sequence of the film surfaces in the presence of an
      electric field upon cooling. The profiles of the associated heat-capacity
      anomalies are found to be strongly thickness dependent and exhibit a novel
      crossover behavior in reduced dimensions. We measure the anticlinic coupling
      between tilted surface layers in the smectic- A phase.

PMID- 11328093
TI  - Electro-optic behavior of liquid-crystal-filled silica opal photonic crystals:
      effect of liquid-crystal alignment.
AB  - Photonic crystals made of nematic liquid crystal intercalated into the void space
      of close-packed silica spheres (synthetic porous opal) exhibit significant
      electric-field-induced shift of the optical Bragg reflection peak when the liquid
      crystal has the long molecular axis oriented parallel to the sphere surfaces. No
      such effect is observed for comparable fields when the long-axis orientation is
      normal to the sphere surfaces.

PMID- 11328094
TI  - Nonstoichiometry and the electrical activity of grain boundaries in SrTiO3.
AB  - A combination of experiments and first-principles calculations is used to show
      that grain boundaries in SrTiO3 are intrinsically nonstoichiometric. Total-energy
      calculations reveal that the introduction of nonstoichiometry into the grain
      boundaries is energetically favorable and results in structures that are
      consistent with atomic-resolution Z-contrast micrographs. Electron energy-loss
      spectra provide direct evidence of nonstoichiometry. These results and
      calculations for nonstoichiometric grain boundaries provide an explanation of the
      microscopic origin of the "double Schottky barriers" that dominate the electrical
      behavior of polycrystalline oxides.

PMID- 11328095
TI  - Coherent external and internal phonons in quasi-one-dimensional organic molecular
      crystals.
AB  - We have directly time resolved coherent phonon oscillations in quasi-one
      dimensional organic crystals of MePTCDI ( N-N'-dimethylperylene-3,4,9,10
      dicarboximide), using femtosecond pump-probe experiments. We observe both higher
      energy oscillations caused by intramolecular vibrations (internal phonons) and,
      for the first time in a quasi-one-dimensional organic system, lower-energy
      modulations which are related to coherent lattice phonons (external phonons). For
      internal A(g) vibrations, the coherence decay time of about 2 ps is almost
      independent of the mode. In contrast, the damping time of the external phonons
      increases strongly with decreasing energy.

PMID- 11328096
TI  - Surface fluctuations of normal and superfluid 3He probed by Wigner solid
      dynamics.
AB  - Electron scattering from surface fluctuations on normal and superfluid 3He has
      been measured by its effect on the linewidth of the low-wave-vector transverse
      magnetophonon mode of the electron crystal (the Wigner solid) floating on the
      helium surface. The relaxation rate becomes anomalously low below 70 mK, and
      reaches a plateau at about 3 times less than its expected value before dropping
      further at the superfluid transition. The absence of such anomalous behavior on
      4He suggests that the effect is specific to liquid 3He.

PMID- 11328098
TI  - Observation of cation reordering during the olivine-spinel transition in fayalite
      by in situ synchrotron X-ray diffraction at high pressure and temperature.
AB  - The olivine-spinel phase transition in fayalite at high pressure and temperature
      has been studied using time-resolved x-ray diffraction. Structure refinements
      show a delay of cation reordering relative to anions during the phase
      transformation and an increase in the cell volume while the cations reorder into
      their sites. A significant stress drop in the sample is observed. This
      experiment, for the first time, quantitatively demonstrates a pseudomartensitic
      transformation: a diffusionless anion sublattice transition coupled with short
      range diffusional cation reordering.

PMID- 11328097
TI  - Local atomic environment of Si suboxides at the SiO2/Si(111) interface determined
      by angle-scanned photoelectron diffraction.
AB  - Local environments of Si suboxides at the interface between a thermally grown
      SiO2 film and Si(111) were studied by angle-scanned photoelectron diffraction. Si
      2p core-level spectra containing chemically shifted components were recorded. The
      components were deconvoluted by least squares fitting and assigned to different
      Si oxidation states. The obtained diffraction patterns of the various suboxides
      exhibit different features. Comparison of these patterns with multiple scattering
      calculations including a multipole R-factor analysis shows that a simple chemical
      abrupt interface model describes well the environment of the suboxides and
      indicates ordered SiO2 close to the interface.

PMID- 11328099
TI  - Power-law statistics for avalanches in a martensitic transformation.
AB  - We devise a two-dimensional model that mimics the recently observed power-law
      distributions for the amplitudes and durations of the acoustic emission signals
      observed during martensitic transformation [Vives et al., Phys. Rev. Lett. 72,
      1694 (1994)]. We include a threshold mechanism, long-range interaction between
      the transformed domains, inertial effects, and dissipation arising due to the
      motion of the interface. The model exhibits thermal hysteresis and, more
      importantly, it shows that the energy is released in the form of avalanches with
      power-law distributions for their amplitudes and durations. Computer simulations
      also reveal morphological features similar to those observed in real systems.

PMID- 11328100
TI  - Ferroelectric Mott-Hubbard phase of organic (TMTTF)2X conductors.
AB  - We present experimental evidence and a corresponding theory for the ferroelectric
      transition in the family of quasi-one-dimensional conductors (TMTTF)2X. We
      interpret this new transition in the frame of the combined Mott-Hubbard state
      taking into account the double action of the spontaneous charge
      disproportionation on the TMTTF molecular stacks and of the X anionic potentials.

PMID- 11328101
TI  - Re-integerization of fractional charges in the correlated quarter-filled band.
AB  - Previous work has demonstrated the existence of soliton defect states with
      charges +/-e/2 in the limits of zero and infinite on-site Coulomb interactions in
      the one-dimensional (1D) quarter-filled band. For large but finite on-site
      Coulomb interaction, the low temperature 2kF bond distortion that occurs within
      the 4kF bond-distorted phase is accompanied by charge ordering on the sites. We
      show that a "re-integerization" of the defect charge occurs in this bond-charge
      density-wave state due to a "binding" of the fractional charges. We indicate
      briefly possible implications of this result for mechanisms of organic
      superconductivity.

PMID- 11328102
TI  - Is the quantum dot at large bias a weak-coupling problem?
AB  - We examine the two-lead Kondo model for a dc-biased quantum dot in the Coulomb
      blockade regime. From perturbative calculations of the magnetic susceptibility,
      we show that the problem retains its strong-coupling nature, even at bias
      voltages larger than the equilibrium Kondo temperature. We give a speculative
      discussion of the nature of the renormalization group flows and the strong
      coupling state that emerges at large voltage bias.

PMID- 11328103
TI  - Simulation of flux lines with columnar pins: bose glass and entangled liquids.
AB  - Using path integral Monte Carlo we simulate a 3D system of up to 1000 magnetic
      flux lines by mapping it onto interacting bosons in (2+1)D. With increasing
      temperatures we find first order melting from an ordered solid to an entangled
      liquid signaled by a finite entropy jump and sharp discontinuities of the defect
      density and the structure factor S(G). For a particular density of strong
      columnar pins the crystal is transformed into a Bose glass phase with patches of
      crystalline order disrupted by the trapped vortices at the pinning sites but with
      no overall positional or orientational order. This glassy phase melts into a
      defected entangled liquid through a continuous transition.

PMID- 11328104
TI  - Long-range proximity effects in superconductor-ferromagnet structures.
AB  - We analyze the proximity effect in a superconductor/ferromagnet (S/F) structure
      with a local inhomogeneity of the magnetization in the ferromagnet near the S/F
      interface. We demonstrate that not only the singlet but also the triplet
      component of the superconducting condensate is induced in the ferromagnet due to
      the proximity effect. The singlet component penetrates into the ferromagnet over
      a short length xi(h) = sqrt[D/h] ( h is the exchange field and D the diffusion
      coefficient), whereas the triplet component penetrates over a long length
      sqrt[D/epsilon] and leads to a significant increase of the ferromagnet
      conductance below the superconducting critical temperature Tc.

PMID- 11328105
TI  - Antiferromagnetic ordering in superconducting YBa2Cu3O6.5.
AB  - Commensurate antiferromagnetic ordering has been observed in the superconducting
      high- Tc cuprate YBa2Cu3O6.5 ( Tc = 55 K) by polarized and unpolarized elastic
      neutron scattering. The magnetic peak intensity exhibits a marked enhancement at
      Tc. Zero-field muon-spin-resonance experiments demonstrate that the staggered
      magnetization is not truly static but fluctuates on a nanosecond time scale.
      These results point towards an unusual spin density wave state coexisting with
      superconductivity.

PMID- 11328106
TI  - Multiple-charge-quanta shot noise in superconducting atomic contacts.
AB  - We have measured shot noise in aluminum atomic point contacts containing a small
      number of conduction channels of known transmissions. In the normal state, we
      find that the noise power is reduced from its Poissonian value and reaches the
      partition limit, as calculated from the transmissions. In the superconducting
      state, the noise reveals the large effective charge associated with each
      elementary transfer process, in excellent agreement with the predictions of the
      quantum theory of multiple Andreev reflections.

PMID- 11328107
TI  - Aharonov-Bohm effect for quasiparticles around a vortex line in a d-wave
      superconductor.
AB  - On the basis of the Bogoliubov-de Gennes theory we develop an analytical
      description of low-energy extended quasiparticle states around an isolated flux
      line in a superconductor with gap nodes. The wave functions of these excitations
      and the corresponding density of states are shown to be strongly influenced by
      the interaction with a pure gauge potential due to the Aharonov-Bohm scenario.

PMID- 11328108
TI  - Mode locking in ac-driven vortex lattices with random pinning.
AB  - We find mode-locking steps in simulated current-voltage characteristics of ac
      driven vortex lattices with random pinning. For low frequencies there is mode
      locking above a finite ac force amplitude, while for large frequencies there is
      mode locking for any small ac force. This is correlated with the nature of
      temporal order in the different regimes in the absence of ac drive. The mode
      locked state is a frozen solid pinned in the moving reference of frame, and the
      depinning from the step shows plastic flow and hysteresis.

PMID- 11328110
TI  - Critical behavior of the two-dimensional Ising susceptibility.
AB  - We report computations of the short- and long-distance (scaling) contributions to
      the square-lattice Ising susceptibility. Both computations rely on summation of
      correlation functions, obtained using nonlinear partial difference equations. In
      terms of a temperature variable tau, linear in T/Tc-1, the short-distance terms
      have the form tau(p)(ln/tau/)q with p> or =q2. A high- and low-temperature series
      of N = 323 terms, generated using an algorithm of complexity O(N6), are analyzed
      to obtain the scaling part, which when divided by the leading /tau/(-7/4)
      singularity contains only integer powers of tau. Contributions of distinct
      irrelevant variables are identified and quantified at leading orders /tau/(9/4)
      and /tau/(17/4).

PMID- 11328109
TI  - Persistence of Li induced Kondo moments in the superconducting state of cuprates.
AB  - Using 7Li NMR shift data, the anomalous local moment induced by spinless Li
      impurities persists below T(c) in YBa 2Cu 3O6+y. In the underdoped regime, the
      moments retain their Curie law below Tc. In contrast, near optimal doping, the
      large Kondo screening observed above Tc (TK = 135 K) is strongly reduced below Tc
      as expected theoretically when the superconducting gap develops. The limited
      spatial extent of the induced moment (on first near neighbor Cu) is not
      drastically modified below Tc, which allows a comparison with STM determination
      of the local density of states. Our results constrain theoretical models of the
      impurity electronic properties.

PMID- 11328111
TI  - Spontaneous plaquette formation in the SU(4) spin-orbital ladder.
AB  - The low-energy properties of the SU(4) spin-orbital model on a two-leg ladder are
      studied by a variety of analytical and numerical techniques. As in the case of
      SU(2) models, there is a singlet-multiplet gap in the spectrum, but the ground
      state is twofold degenerate. An interpretation in terms of SU(4)-singlet
      plaquettes is proposed. The implications for general two-dimensional lattices are
      outlined.

PMID- 11328112
TI  - Resonant enhancements at nonmagnetic ions: new possibilities for magnetic X-ray
      scattering.
AB  - Synchrotron experiments with uranium antiferromagnetic compounds have discovered
      large ( >1000) enhancements of the magnetic scattering intensities at the K edges
      of nominally nonmagnetic anions, e.g., Ga and As. The width in energy, the
      position with respect to the white line, and the azimuthal and polarization
      dependencies permit one to associate the signal with transitions of E1 dipole
      symmetry from 1s to 4p states. In momentum space, the signal exhibits long-range
      order at the antiferromagnetic wave vector. We discuss possible channels capable
      of generating the observed enhancements.

PMID- 11328113
TI  - Resolving complex atomic-scale spin structures by spin-polarized scanning
      tunneling microscopy.
AB  - The spin-polarized scanning tunneling microscope (SP-STM) operated in the
      constant current mode is proposed as a powerful tool to investigate complex
      atomic-scale magnetic structures of otherwise chemically equivalent atoms. The
      potential of this approach is demonstrated by successfully resolving the magnetic
      structure of Cr/Ag(111), which is predicted on the basis of ab initio vector spin
      density calculations to be a coplanar noncollinear periodic 120 degrees Neel
      structure. Different operating modes of the SP-STM are discussed on the basis of
      the model of Tersoff and Hamann.

PMID- 11328114
TI  - Charge dynamics of 2H- TaSe2 along the less-conducting c-axis.
AB  - We present an optical study of 2H-TaSe2 along the less conducting c-axis. This
      dichalcogenide compound belongs to a large class of conductors called "bad
      metals" (with a mean free path smaller than the lattice constant along the c
      axis), which also includes the superconducting cuprates. The optical response
      shows the progressive development of a pseudogaplike feature with decreasing
      temperature. The spectral weight lost by the opening of such a pseudogap goes
      into the narrow Drude component, developing at low frequency and temperature.
      There is no violation of the sum rule in 2H-TaSe2 contrary to the cuprates.

PMID- 11328115
TI  - Transverse josephson plasma mode in T* cuprate superconductors.
AB  - A transverse optical plasma mode is observed at far-infrared frequencies within
      the superconducting gap region by measuring the c-axis optical reflectivity for
      single crystals of T* cuprate superconductors SmLa0.85Sr0.15CuO4-delta and
      Nd1.4Sr0.4Ce0.2CuO4-delta. These T* cuprates have two different insulating layers
      sandwiching the superconducting CuO2 planes, leading to two longitudinal
      plasmons. Also, the transverse mode is directly observed due to the coupling of
      the infrared radiation with the current perpendicular to the superconducting
      layers which are regarded as an alternating array of two inequivalent Josephson
      junctions.

PMID- 11328116
TI  - Observation of the transverse optical plasmon in SmLa0.8Sr0.2CuO4-delta.
AB  - We present microwave and infrared measurements on SmLa0.8Sr0.2CuO4-delta, which
      are direct evidence for the existence of a transverse optical plasma mode,
      observed as a peak in the c-axis optical conductivity. This mode appears as a
      consequence of the existence of two different intrinsic Josephson couplings
      between the CuO2 layers, one with a Sm2O2 block layer, and the other one with a
      (La,Sr)2O2-delta block layer. From the frequencies and the intensities of the
      collective modes we determine the value of the compressibility of the two
      dimensional electron fluid in the copper oxygen planes.

PMID- 11328117
TI  - Coherent control of optical emission from a conjugated polymer.
AB  - We have observed that resonant Rayleigh scattering dominates the emission from
      poly(p-phenylene vinylene) excited with photons at energies below the threshold
      at which excitonic migration is reduced. The intensity of the resonant emission
      decays exponentially with a lifetime of up to 450 fs after pulsed excitation. The
      coherent nature of the emission was confirmed by angular variations in the far
      field emission intensity-bright and dark speckles. Persistence of a coherent
      polarization was demonstrated by coherent control using phase-locked pulses.

PMID- 11328118
TI  - Spin-polarized electrons in collisions of multicharged nitrogen ions with a
      magnetized Fe(001) surface.
AB  - We report on the first spin-resolved energy spectra for the emission of electrons
      during grazing scattering of 150 keV multicharged nitrogen ions from a magnetized
      Fe(001) surface. A substantial spin polarization for KLL Auger electrons emitted
      in the final stage of the neutralization sequence during the interaction of
      multicharged ions with a metal surface is observed. We conclude from our data
      that the projectile L shell is dominantly populated by electrons from the
      conduction band of the target. For low energy electrons we find an increase of
      their spin polarization with an increase of the projectile charge.

PMID- 11328119
TI  - Measurement of persistence in 1D diffusion.
AB  - Using a novel NMR scheme we observed persistence in 1D gas diffusion. Analytical
      approximations and numerical simulations have indicated that for an initially
      random array of spins undergoing diffusion, the probability p(t) that the average
      spin magnetization in a given region has not changed sign (i.e., "persists") up
      to time t follows a power law t(-straight theta), where straight theta depends on
      the dimensionality of the system. Using laser-polarized 129Xe gas, we prepared an
      initial "quasirandom" 1D array of spin magnetization and then monitored the
      ensemble's evolution due to diffusion using real-time NMR imaging. Our
      measurements are consistent with analytical and numerical predictions of straight
      theta approximately 0.12.

PMID- 11328120
TI  - Entangled quantum states as direction indicators.
AB  - We consider the use of N spin-1/2 particles for indicating a direction in space.
      If N>2, their optimal state is entangled. For large N, the mean square error
      decreases as N-2 (rather than N-1 for parallel spins).

PMID- 11328121
TI  - Dynamic pattern formation in a vesicle-generating microfluidic device.
AB  - Spatiotemporal pattern formation occurs in a variety of nonequilibrium physical
      and chemical systems. Here we show that a microfluidic device designed to produce
      reverse micelles can generate complex, ordered patterns as it is continuously
      operated far from thermodynamic equilibrium. Flow in a microfluidic system is
      usually simple-viscous effects dominate and the low Reynolds number leads to
      laminar flow. Self-assembly of the vesicles into patterns depends on channel
      geometry and relative fluid pressures, enabling the production of motifs ranging
      from monodisperse droplets to helices and ribbons.

PMID- 11328122
TI  - Exciton delocalization probed by excitation annihilation in the light-harvesting
      antenna LH2.
AB  - Singlet-singlet annihilation is used to study exciton delocalization in the light
      harvesting antenna complex LH2 (B800-B850) from the photosynthetic purple
      bacterium Rhodobacter sphaeroides. The characteristic femtosecond decay constants
      of the high intensity isotropic and the low intensity anisotropy kinetics of the
      B850 ring are related to the hopping time tau(h) and the coherence length N(coh)
      of the exciton. Our analysis yields N(coh) = 2.8+/-0.4 and tau(h) = 0.27+/-0.05
      ps. This approach can be seen as an extension to the concept of the spectroscopic
      ruler.

PMID- 11328123
TI  - Viscoelasticity of solutions of motile polymers.
AB  - We explore the linear viscoelastic response of an entangled, isotropic solution
      of polar semiflexible polymers with active, motile centers which generate
      longitudinal motion. Because of the activity of these centers, the short-time
      modulus displays two novel power-law regimes: Initially G(t) proportional to t(
      1/8), then the response is "Rouse-like" with G(t) proportional to t(-1/2). At
      longer times we find accelerated relaxation due to directed reptation, resulting
      in a reduced low frequency viscosity.

PMID- 11328124
TI  - Existence and stability of persistent states in large neuronal networks.
AB  - We study the existence and stability of persistent states in large networks of
      quadratic integrate-and-fire neurons. The networks consist of two populations,
      one excitatory and one inhibitory. The stability of the asynchronous state is
      studied analytically. Our study demonstrates the role of recurrent inhibition and
      inhibitory-inhibitory interactions in stable persistent activity in large
      neuronal networks.

PMID- 11328125
TI  - Bistability in pulse propagation in networks of excitatory and inhibitory
      populations.
AB  - We study the propagation of traveling solitary pulses in one-dimensional networks
      of excitatory and inhibitory integrate-and-fire neurons. Slow pulses, during
      which inhibitory cells fire well before neighboring excitatory cells, can
      propagate along the network at intermediate inhibition levels. At higher levels,
      they destabilize via a Hopf bifurcation. There is a bistable parameter regime in
      which both fast and slow pulses can propagate. Lurching pulses with
      spatiotemporal periodicity can propagate in regimes for which continuous pulses
      do not exist.

PMID- 11328126
TI  - Population dynamics: Poisson approximation and its relation to the Langevin
      process.
AB  - We discuss how to simulate a stochastic evolution process in terms of difference
      equations with Poisson distributions of independent events when the problem is
      naturally described by discrete variables. For large populations the Poisson
      approximation becomes a discrete integration of the Langevin approximation [T. G.
      Kurtz, J. Appl. Prob. 7, 49 (1970); 8, 344 (1971)]. We analyze when the latter
      gives a reasonable representation of the original evolution for finite size
      systems. A simple example of an epidemic process is used to organize the
      discussion and to perform statistical tests that underline the goodness of the
      proposed method.

PMID- 11328127
TI  - Comment on "double diffusive convection in freely suspended soap films".

PMID- 11328129
TI  - Comment on "Efimov states for 4He trimers?".

PMID- 11328131
TI  - Comment on "measurement of the intrinsic dissipation of a macroscopic system in
      the quantum regime".

PMID- 11328133
TI  - Quantum tomography for measuring experimentally the matrix elements of an
      arbitrary quantum operation.
AB  - Quantum operations describe any state change allowed in quantum mechanics,
      including the evolution of an open system or the state change due to a
      measurement. We present a general method based on quantum tomography for
      measuring experimentally the matrix elements of an arbitrary quantum operation.
      As input the method needs only a single entangled state. The feasibility of the
      technique for the electromagnetic field is shown, and the experimental setup is
      illustrated based on homodyne tomography of a twin beam.

PMID- 11328134
TI  - Atomic four-wave mixing: fermions versus bosons.
AB  - We compare four-wave mixing in quantum degenerate gases of bosonic and fermionic
      atoms. We find that matter-wave gratings formed from either bosonic or fermionic
      atoms can in principle exhibit nearly identical Bragg scattering and four-wave
      mixing properties. This implies that effects such as coherent matter-wave
      amplification and superradiance can occur in degenerate Fermi gases. This effect
      is due to constructive many-particle quantum interferences, which in the boson
      case are interpreted as "Bose enhancement."

PMID- 11328135
TI  - Does matter wave amplification work for fermions?
AB  - We discuss the relationship between bosonic stimulation, density fluctuations,
      and matter wave gratings. It is shown that enhanced stimulated scattering, matter
      wave amplification, and atomic four-wave mixing do not require macroscopic
      occupation of a single quantum state. These processes are in principle possible
      for fermionic or nondegenerate samples, if they are prepared in a cooperative
      state. In practice, there are limitations due to short coherence times.

PMID- 11328136
TI  - Condensate fragmentation in a new exactly solvable model for confined bosons.
AB  - Based on Richardson's exact solution of the multilevel pairing model we derive a
      new class of exactly solvable models for the finite boson system. As an example
      we solve a particular Hamiltonian which displays a transition to a fragmented
      condensate for repulsive pairing interaction.

PMID- 11328137
TI  - Controlled collapse of a Bose-Einstein condensate.
AB  - The point of instability of a Bose-Einstein condensate (BEC) due to attractive
      interactions was studied. Stable 85Rb BECs were created and then caused to
      collapse by slowly changing the atom-atom interaction from repulsive to
      attractive using a Feshbach resonance. At a critical value, an abrupt transition
      was observed in which atoms were ejected from the condensate. By measuring the
      onset of this transition as a function of number and attractive interaction
      strength, we determined the stability condition to be N(absolute value of a) /
      a(ho) = 0.459+/-0.012+/-0.054, slightly lower than the predicted value of 0.574.

PMID- 11328138
TI  - Scale dependent dimension of luminous matter in the universe.
AB  - We suggest a geometrical model for the distribution of luminous matter in the
      Universe, where the apparent dimension, D(l), increases linearly with the
      logarithm of the scale l. Beyond the correlation length, xi, the Universe is
      homogeneous, and D = 3. Comparison with data from the SARS redshift catalog, and
      the LEDA database provides a good fit with a correlation length xi approximately
      300 Mpc. This type of scaling structure was recently discovered in a simple
      reaction-diffusion "forest-fire" model, indicating a broad class of scaling
      phenomena.

PMID- 11328139
TI  - Signature change on the brane.
AB  - We explore the possibility of having a good description of classical signature
      change in the brane scenario.

PMID- 11328140
TI  - Randall-Sundrum model for self-tuning the cosmological constant.
AB  - The vanishing cosmological constant in the four-dimensional space-time is
      obtained in a 5D Randall-Sundrum model with a brane (B1) located at y = 0. The
      matter fields can be located at the brane. For settling any vacuum energy
      generated at the brane to zero, we need a three-index antisymmetric tensor field
      A(MNP) with a specific form for the Lagrangian. For the self-tuning mechanism,
      the bulk cosmological constant should be negative.

PMID- 11328141
TI  - Flavor-dependent supersymmetric phases and CP asymmetry in B --> X(s)gamma
      decays.
AB  - We study the direct CP asymmetry in B-->X(s)gamma decay in supersymmetric models
      with nonuniversal A terms. We show that the flavor-dependent phases of the A
      terms, unlike the flavor-independent ones, can give rise to a large contribution
      to the CP asymmetry while respecting the experimental bounds on the branching
      ratio of B-->X(s)gamma decay and the electric dipole moments of the electron and
      neutron. The CP asymmetry of this decay is predicted to be much larger than the
      standard model prediction in a wide region of the parameter space. In particular,
      it can be of order 10%-15% which can be accessible at B factories.

PMID- 11328142
TI  - Low-energy supersymmetry and the Tevatron bottom-quark cross section.
AB  - A long-standing discrepancy between the bottom-quark production cross section and
      predictions of perturbative quantum chromodynamics is addressed. We show that
      pair production of light gluinos, of mass 12 to 16 GeV, with two-body decays into
      bottom quarks and light bottom squarks, yields a bottom-quark production rate in
      agreement with hadron collider data. We examine constraints on this scenario from
      low-energy data and make predictions that may be tested at the next run of the
      Fermilab Tevatron collider.

PMID- 11328144
TI  - Measuring the P-odd pion-nucleon coupling h((1))(piNN) in pi(+)-photoproton
      production near threshold.
AB  - We show that gamma-->p-->pi(+)n in the threshold region is an excellent candidate
      for measuring the leading parity-violating pion-nucleon coupling h((1))(piNN) to
      an uncertainty of 20% if it has a natural size from dimensional analysis. The
      conclusion is based on a large unpolarized cross section, a new low-energy
      theorem for the photon polarization asymmetry at the threshold A(gamma)/(th) =
      square root of 2 f(pi)(mu(p)-mu(n))h((1))(piNN)/g(A)m(N) approximately
      h((1))(piNN)/2, and its strong dominance at forward and backward angles in the
      threshold region.

PMID- 11328143
TI  - TeV strings and the neutrino-nucleon cross section at ultrahigh energies.
AB  - In scenarios with the fundamental unification scale at the TeV one expects string
      excitations of the standard model fields at accessible energies. We study the
      neutrino-nucleon cross section in these models. We show that duality of the
      scattering amplitude forces the existence of a tower of massive leptoquarks that
      mediate the process in the s channel. Using the narrow-width approximation we
      find a sum rule for the production rate of resonances with different spin at each
      mass level. We show that these contributions can increase substantially the
      standard model neutrino-nucleon cross section, although they seem insufficient to
      explain the cosmic ray events above the Greisen-Zatsepin-Kuz'min cutoff energy.

PMID- 11328146
TI  - Pathways to rare baryonic B decays.
AB  - We point out new ways to search for charmless baryonic B decays and suggest that
      enhanced baryon production is favored by reduced energy release on the baryon
      side. Thus B-->eta(')+baryon pairs might be larger than Kpi/pipi modes; the
      argument may be extended to B-->gamma+X(s), and perhaps to lnu+X(u). Guess
      estimates give some branching ratios in the 10(-3)- 10(-6) range, with confidence
      gained from the recent observation of B-->D(*)pn, D(*)pppi not far below D(*)pi
      and D(*)rho rates. Observation of modes proposed here would help clarify the
      dynamics of weak decays involving baryons, while the self-analyzing prowess of
      Lambda decay can be helpful in CP- and T-violation studies.

PMID- 11328147
TI  - Is anomalous production of omega and omega; evidence for disoriented chiral
      condensates?
AB  - No conventional picture of nucleus-nucleus collisions has yet been able to
      explain the abundance of Omega and Omega; hadrons in central collisions between
      Pb nuclei at 158A GeV at the CERN SPS. We argue that this is evidence that they
      are produced as topological defects arising from the formation of disoriented
      chiral condensates with an average domain size of about 2 fm.

PMID- 11328149
TI  - Determination of the (76)Ge double beta decay Q value.
AB  - The Q value of the (76)Ge double beta decay has been determined by measuring the
      masses of (76)Ge and (76)Se in a Penning trap using neon- and fluorinelike ions.
      The obtained masses are 75.921 402 758(96) u and 75.919 213 795(81) u,
      respectively. The systematic errors of these two determinations are nearly equal,
      and therefore, the remaining systematic uncertainty of the Q value is drastically
      reduced. A Q value of 2 039.006(50) keV was obtained improving the accuracy of
      the accepted value by a factor of 6.

PMID- 11328148
TI  - Observation of spin-orbit splitting in lambda single-particle states.
AB  - The spin-orbit splitting of Lambda single-particle states in (13)(Lambda)C was
      measured. The 13C(K-,pi(-))(13)(Lambda)C reaction was used to excite both the
      1/2(-) and 3/2(-) states simultaneously, which have predominantly 12C(0(+)) x
      p(Lambda) configuration. gamma rays from the states to the ground state were
      measured in coincidence with the pi(-)'s, by which ls splitting was found to be
      152+/-54(stat)+/-36(syst) keV. The value is 20-30 times smaller than exhibited by
      the ls splitting in the nuclear shell model. This value gives us new insight into
      the YN interaction.

PMID- 11328150
TI  - Event-by-event analysis of collision-induced cluster-ion fragmentation:
      sequential monomer evaporation versus fission reactions.
AB  - The most abundant decay channels have been studied quantitatively for high-energy
      (60 keV/amu) cluster ions H (3) (+)(H (2))(m = 1-14) colliding with He atoms
      employing a recently developed multicoincidence technique for the simultaneous
      detection of the correlated fragments on an event-by-event basis. This allows us
      to identify decay reactions and their underlying decay mechanisms responsible for
      the occurrence of the U-shaped fragmentation pattern.

PMID- 11328151
TI  - Generation of continuous variable Einstein-Podolsky-Rosen entanglement via the
      Kerr nonlinearity in an optical fiber.
AB  - We report on the generation of a continuous variable Einstein-Podolsky-Rosen
      (EPR) entanglement using an optical fiber interferometer. The Kerr nonlinearity
      in the fiber is exploited for the generation of two independent squeezed beams.
      These interfere at a beam splitter and EPR entanglement is obtained between the
      output beams. The correlation of the amplitude (phase) quadratures is measured to
      be 4.0+/-0.2 (4.0+/-0.4) dB below the quantum noise limit. The sum criterion for
      these squeezing variances 0.80+/-0.03<2 verifies the nonseparability of the
      state. The product of the inferred uncertainties for one beam (0.64+/-0.08) is
      well below the EPR limit of unity.

PMID- 11328145
TI  - Evidence of New States Decaying into Xi(*)(c)pi.
AB  - Using 13.7 fb(-1) of data recorded by the CLEO detector at Cornell Electron
      Storage Ring, we report evidence of two new charmed baryons: one decaying into
      Xi(0')(c)pi(+) with the subsequent decay Xi(0')(c)-->Xi(0)(c)gamma, and its
      isospin partner decaying into Xi(+')(c)pi(-) followed by Xi(+')(c)-
      >Xi(+)(c)gamma. We measure the following mass differences for the two states:
      M(Xi(0)(c)gammapi(+))-M(Xi(0)(c)) = 318.2+/-1.3+/-2.9 MeV and M(Xi(+)(c)gammapi(
      ))-M(Xi(+)(c)) = 324.0+/-1.3+/-3.0 MeV. We interpret these new states as the J(P)
      = 1 / 2(-) Xi(c1) particles, the charmed-strange analogs of the
      Lambda(+)(c1)(2593).

PMID- 11328152
TI  - Inhibition of decoherence due to decay in a continuum.
AB  - We propose a scheme for slowing down decay into a continuum. We make use of a
      sequence of ultrashort 2pi pulses applied on an auxiliary transition of the
      system so that there is a destructive interference between the two transition
      amplitudes--one before the application of the pulse and the other after the
      application of the pulse. We give explicit results for a structured continuum.
      Our scheme can also inhibit unwanted transitions.

PMID- 11328153
TI  - Resonant radiation pressure on neutral particles in a waveguide.
AB  - A theoretical analysis of electromagnetic forces on neutral particles in a hollow
      waveguide is presented. We show that the effective scattering cross section of a
      very small (Rayleigh) particle can be strongly modified inside a waveguide. The
      coupling of the scattered dipolar field with the waveguide modes induces a
      resonant enhanced backscattering state of the scatterer-guide system close to the
      onset of new modes. The particle effective cross section can then be as large as
      the wavelength even far from any transition resonance. As we will show, a small
      particle can be strongly accelerated along the guide axis while being highly
      confined in a narrow zone of the cross section of the guide.

PMID- 11328154
TI  - Phase diagram for the Winfree model of coupled nonlinear oscillators.
AB  - In 1967 Winfree proposed a mean-field model for the spontaneous synchronization
      of chorusing crickets, flashing fireflies, circadian pacemaker cells, or other
      large populations of biological oscillators. Here we give the first bifurcation
      analysis of the model, for a tractable special case. The system displays rich
      collective dynamics as a function of the coupling strength and the spread of
      natural frequencies. Besides incoherence, frequency locking, and oscillator
      death, there exist hybrid solutions that combine two or more of these states. We
      present the phase diagram and derive several of the stability boundaries
      analytically.

PMID- 11328155
TI  - Ultrasonic wedges for elastic wave bending and splitting without requiring a full
      band gap.
AB  - We present a novel twinned-square periodic structure for ultrasonic wave bending
      and splitting that does not require the existence of a complete band gap and
      plays the role of an ultrasonic wedge. The device allows 45 degrees bending of
      waves and by adequately switching the twinned structure to an ultrasonic crystal
      90 degrees bending is achieved. An extreme refraction law at the grain boundaries
      is experimentally observed.

PMID- 11328156
TI  - Dynamic sand dunes.
AB  - When sand falling in the spacing between two plates goes past an obstacle, a
      dynamic dune with a parabolic shape and an inner triangular region of nonflowing
      or slowly creeping sand forms. The angle of the triangular zone increases with
      the height of the dune and saturates at a value determined by the geometry of the
      cell. The width of the dune, related to the radius of curvature at the tip, shows
      universal features versus its height rescaled by geometrical parameters. The
      velocity profile in the flowing part is determined and found to be nonlinear. The
      parabolic shape can be accounted for using a simple driven convection-diffusion
      equation for the interface.

PMID- 11328157
TI  - Air entrainment through free-surface cusps.
AB  - In many industrial processes, such as pouring a liquid or coating a rotating
      cylinder, air bubbles are entrapped inside the liquid. We propose that this is
      due to air being drawn into the narrow channel of a cusp singularity that
      generically forms on free surfaces. Since the width of the cusp is exponentially
      small in the driving strength, even the minute viscosity of air is enough to
      destroy the stationary solution, and a sheet emanates from the cusp's tip,
      through which air is entrained. Our analytical theory is confirmed by
      quantitative comparison with numerical simulations of the flow equations, and is
      found to be in qualitative agreement with experimental observation.

PMID- 11328158
TI  - Generalized hydrodynamic theory of shock waves: Mach-number dependence of inverse
      shock width for nitrogen gas.
AB  - A generalized hydrodynamic theory of shock wave structures is presented for rigid
      diatomic gases. The theory yields shock solutions for all Mach numbers. The
      accuracy of the theory is examined for nitrogen gas as an example. Excellent
      agreement with experiment is obtained for the inverse shock widths for the entire
      range of Mach number studied by experiment. The comparison made shows that we are
      now in possession of a successful continuum theory of shock waves in molecular
      gases for all Mach numbers.

PMID- 11328159
TI  - Synchronized chaos in geophysical fluid dynamics.
AB  - Fluid flow fields in a pair of quasi-two-dimensional channel models, each of
      which vacillates chaotically between distinct flow regimes, synchronize if only
      the small-scale eddy components of the two flows are coupled. The synchronization
      behavior also governs the relationship between different sectors of the same
      continuous channel. Where there is no natural boundary to define the sectors, but
      the sectors are separately forced, the channel can be represented as two
      coextensive, coupled channel models with different forcing terms. Generalized
      synchronization of these two systems implies a relationship between the Atlantic
      and Pacific sectors of the Earth's climate system.

PMID- 11328160
TI  - Rayleigh-Benard percolation transition study of thermal convection in porous
      media: numerical simulation and NMR experiments.
AB  - Thermal convection was studied as a function of the porosity in random-site
      percolation model objects in a Rayleigh-Benard configuration. NMR velocity
      mapping experiments and numerical simulations using the finite-volume method are
      compared. Velocity histograms were evaluated and can be described by power laws
      in a wide range. The maximum velocity as a function of the porosity indicates a
      combined percolation/Rayleigh-Benard transition.

PMID- 11328161
TI  - Transient enhancement and detuning of laser-driven parametric instabilities by
      particle trapping.
AB  - Kinetic simulations of backward stimulated Raman scattering (BSRS), where the
      Langmuir wave coherence time is greater than the bounce time for trapped
      electrons, yield transient reflectivity levels far above those predicted by
      fluidlike models. Electron trapping reduces the Langmuir wave damping and lowers
      the Langmuir wave frequency, and leads to a secular phase shift between the
      Langmuir wave and the BSRS beat ponderomotive force. This phase shift detunes and
      saturates BSRS and a similar effect, due to ion trapping, is the saturation
      mechanism for backward stimulated Brillouin scattering. Competition with forward
      SRS is discussed.

PMID- 11328163
TI  - Lithium dynamics in LiMn2O4 probed directly by two-dimensional (7)Li NMR.
AB  - LiMn2O4 has been studied using magic-angle-spinning nuclear magnetic resonance
      (MAS NMR). 1D MAS NMR shows three Li resonances assigned to different
      crystallographic sites. At low temperatures an extra peak appears, indicating
      charge ordering of Mn3+ and Mn4+. Direct observation of the lithium dynamics was
      possible using rotor-synchronized 2D exchange NMR. A millisecond time scale
      exchange of lithium starts around 285 K between the 8a and the 16c site. At 380 K
      lithium even starts to hop between more than two sites. The activation energies
      and Li jump rates are derived and are in agreement with those determined
      macroscopically.

PMID- 11328162
TI  - Generalized scaling laws of the formation and effects of plasma-confining
      potentials for tandem-mirror operations in GAMMA 10.
AB  - The main operations from 1979 to 2000 in the GAMMA 10 tandem-mirror,
      characterized in terms of the high-potential mode having kV-order plasma
      confining potentials and the hot-ion mode yielding fusion neutrons with 10-20 keV
      bulk-ion temperatures, are summarized and generalized as a result of scalings of
      the formation and the effects of the potentials. The wide validity of potential
      formation physics from Cohen's theory and the validity of the generalized
      Pastukhov's theory for the effects of thermal-barrier potentials on electron
      confinement are verified and consolidated through electron-energy balance.

PMID- 11328164
TI  - Low-temperature heat transfer in nanowires.
AB  - A new regime of low-temperature heat transfer in suspended nanowires is
      predicted. It takes place when (i) only "acoustic" phonon modes of the wire are
      thermally populated and (ii) phonons are subject to the effective elastic
      scattering. Qualitatively, the main peculiarities of heat transfer originate due
      to the appearance of the flexural modes with high density of states in the wire
      phonon spectrum. They give rise to the T(1/2) temperature dependence of the wire
      thermal conductance. Experimental situations where the new regime is likely to be
      detected are discussed.

PMID- 11328165
TI  - Helium-4 Bose fluids formed in one-dimensional 18 A diameter pores.
AB  - Bose fluids restricted in one dimension (1D) are realized by adsorbing 4He atoms
      on the 1D pore walls with a diameter of about 18 A. The Bose fluid appears above
      an adsorbed amount after the pore walls are coated with the inert 4He atoms. Heat
      capacity of the fluid was observed to have a temperature-linear term at low
      temperatures. This corresponds to the phonon heat capacity of the Bose fluid in
      the 1D pores. We estimate the phonon velocity and the interaction of the 1D Bose
      fluid.

PMID- 11328166
TI  - Capillary force on colloidal particles in a freely suspended liquid thin film.
AB  - The dynamic behavior of micron-sized polystyrene latex particles confined in a
      free-standing liquid film is experimentally studied. When the thickness of the
      film is less than the particle diameter and varies depending on position, the
      particles are accelerated toward the thicker region. Using a simple geometrical
      model and hydrodynamic theory, we calculate the capillary force on the particle.
      The drag coefficient of the particle is found to depend on the thickness of the
      film from the value of near zero to the Stokes' drag coefficient.

PMID- 11328167
TI  - Structure and dynamics of dense monolayers of no adsorbed on Rh(111) in
      equilibrium with the gas phase in the Torr pressure range.
AB  - Using scanning tunneling microscopy, we show the phase transition between new
      structures of NO on Rh(111) in equilibrium with the gas phase near 300 K, in the
      Torr pressure range. Two phases with (2 x 2) and (3 x 3) periodicity transform
      into each other as the pressure and temperature change around the equilibrium P-T
      line. By measuring P and T at coexistence, we determined the heat of adsorption
      in the (3 x 3) structure. From the phase boundary dynamics, the activation energy
      barrier between phases were estimated. The results demonstrate that unique
      information can be obtained from high-pressure and high-temperature studies.

PMID- 11328168
TI  - Atomic resolution noncontact atomic force and scanning tunneling microscopy of
      TiO2(110)-(1 x 1) and - (1 x 2): simultaneous imaging of surface structures and
      electronic states.
AB  - We present simultaneous imaging of TiO2(110)-(1 x 1) and - (1 x 2) using
      noncontact atomic force microscopy (NC-AFM) and scanning tunneling microscopy
      (STM). The surface topography was imaged under NC-AFM feedback, while the surface
      electronic states were imaged by STM. The image contrasts of NC-AFM and STM were
      antiphase in (1 x 1) and in phase in (1 x 2). The uppermost oxygen and Ti atoms
      underneath were, respectively, imaged by NC-AFM and STM. The NC-AFM image
      contrast was close to the true surface topography in (1 x 2), but reduced in (1 x
      1).

PMID- 11328169
TI  - Kinetics and energetics of oligomer desorption from surfaces.
AB  - The dynamics of oligomer desorption from surfaces has been studied by measuring
      the desorption kinetics of a set of straight chain alkanes [ H(CH2)(n)H, with n =
      5 to 60] from the surface of single crystalline graphite. Desorption is observed
      to be a first-order process and the preexponent of the desorption rate constant
      has a value nu = 10(19.6+/-0.5) sec(-1) and is independent of the oligomer chain
      length. More interestingly, we find that the barrier to desorption has a
      nonlinear dependence on chain length and takes the form DeltaE(double
      dagger)(des) = A+Bn(alpha), with the exponent alpha = 0.50+/-0.01.

PMID- 11328170
TI  - Atomic scale oxidation of a complex system: O2/alpha-SiC(0001)-( 3 x 3).
AB  - The atomic scale oxidation of the alpha-SiC(0001)-(3 x 3) surface is investigated
      by atom-resolved scanning tunneling microscopy, core level synchrotron radiation
      based photoemission spectroscopy, and infrared absorption spectroscopy. The
      results reveal that the initial oxidation takes place through the relaxation of
      lower layers, away from the surface dangling bond, in sharp contrast to silicon
      oxidation.

PMID- 11328171
TI  - Metal-insulator and structural phase transition observed by ESR spectroscopy and
      x-ray diffraction in KC60.
AB  - We have performed electron spin resonance (ESR) spectroscopy and x-ray
      diffraction experiments at low temperature on KC60 single crystals. ESR data
      reveal the occurrence of a metal-insulator phase transition at about 50 K. In the
      same temperature range, we observe the stabilization of a superstructure which
      doubles the volume of the unit cell. We suggest that displacements of the K atoms
      and a modulation of the C60 charge may be involved in the mechanism of this phase
      transition. These results shed new light on the subtle interplay of structure,
      dimensionality, and electronic properties in the AC60 fullerides.

PMID- 11328172
TI  - High performance thermoelectric Tl9BiTe6 with an extremely low thermal
      conductivity.
AB  - Tl 9BiTe (6) exhibits a thermoelectric figure of merit of ZT approximately 1.2
      around 500 K, which significantly exceeds the state-of-the-art materials in this
      temperature range. The extraordinary thermoelectric performance is mainly due to
      the extremely low thermal conductivity of Tl 9BiTe (6) [ 0.39 W/(m times K) at
      300 K]. In fact, the minimum lifetime of the phonons has to be taken into account
      to describe the thermal conductivity data.

PMID- 11328173
TI  - Moving Wigner glasses and smectics: dynamics of disordered Wigner crystals.
AB  - We examine the dynamics of driven classical Wigner solids interacting with
      quenched disorder from charged impurities. For strong disorder, the initial
      motion is plastic, in the form of crossing winding channels. For increasing
      drive, there is a reordering into a moving Wigner smectic with the electrons
      moving in separate 1D channels. These different dynamic phases can be related to
      the conduction noise and I(V) curves. For strong disorder, we show criticality in
      the voltage onset just above depinning. We obtain the dynamic phase diagram for
      driven Wigner solids and demonstrate a finite threshold of force for transverse
      sliding, recently observed experimentally.

PMID- 11328174
TI  - Conversion of spin into directed electric current in quantum wells.
AB  - A nonequilibrium population of spin-up and spin-down states in quantum well
      structures has been achieved applying circularly polarized radiation. The spin
      polarization results in a directed motion of free carriers in the plane of a
      quantum well perpendicular to the direction of light propagation. Because of the
      spin selection rules the direction of the current is determined by the helicity
      of the light and can be reversed by switching the helicity from right to left
      handed. A microscopic model is presented which describes the origin of the photon
      helicity driven current. The model suggests that the system behaves as a battery
      which generates a spin polarized current.

PMID- 11328175
TI  - Evidence of electron fractionalization from photoemission spectra in the high
      temperature superconductors.
AB  - In the normal state of the high temperature superconductors
      Bi(2)Sr(2)CaCu(2)O(8+delta) and La2(-x)Sr(x)CuO4, and in the related "stripe
      ordered" material, La(1.25)Nd(0.6)Sr(0.15)CuO4, there is sharp structure in the
      measured single hole spectral function, A<(k-->,omega), considered as a function
      of k--> at fixed small binding energy omega. At the same time, as a function of
      omega at fixed k--> on much of the putative Fermi surface, any structure in A<(k-
      >,omega), other than the Fermi cutoff, is very broad. This is characteristic of
      the situation in which there are no stable excitations with the quantum numbers
      of the electron, as is the case in the one-dimensional electron gas.

PMID- 11328176
TI  - Superconductivity of MgB2: covalent bonds driven metallic.
AB  - A series of calculations on MgB2 and related isoelectronic systems indicates that
      the layer of Mg2+ ions lowers the nonbonding B pi ( p(z)) bands relative to the
      bonding sigma ( sp(x)p(y)) bands compared to graphite, causing sigma-->pi charge
      transfer and sigma band doping of 0.13 holes/cell. Because of their two
      dimensionality the sigma bands contribute strongly to the Fermi level density of
      states. Calculated deformation potentials of gamma point phonons identify the B
      bond stretching modes as dominating the electron-phonon coupling.
      Superconductivity driven by sigma band holes is consistent with the report of
      destruction of superconductivity by doping with Al.

PMID- 11328178
TI  - Scanning tunneling spectroscopy in MgB2.
AB  - We present scanning tunneling microscopy measurements of the surface of
      superconducting MgB2 with a critical temperature of 39 K. In zero magnetic field
      the conductance spectra can be analyzed in terms of the standard BCS theory with
      a smearing parameter gamma. The value of the superconducting gap is 5 meV at 4.2
      K, with no experimentally significant variation across the surface of the sample.
      The temperature dependence of the gap follows the BCS form, fully consistent with
      phonon-mediated superconductivity in this novel superconductor. The application
      of a magnetic field induces strong pair breaking as seen in the conductance
      spectra in fields up to 6 T.

PMID- 11328177
TI  - Superconducting gap and strong in-plane anisotropy in untwinned YBa2Cu3O(7
      delta).
AB  - With significantly improved sample quality and instrumental resolution, we
      clearly identify in the ( pi,0) photoemission spectra from YBa(2)Cu(3)O(6.993),
      in the superconducting state, the long-sought "peak-dip-hump" structure. This
      advance allows us to investigate the large a-b anisotropy of the in-plane
      electronic structure including, in particular, a 50% difference in the magnitude
      of the superconducting gap that scales with the energy position of the hump
      feature. This anisotropy, likely induced by the presence of the CuO chains,
      raises serious questions about attempts to quantitatively explain the
      YBa(2)Cu(3)O(7-delta) data from various experiments using models based on a
      perfectly square lattice.

PMID- 11328179
TI  - Creep of superconducting vortices in the limit of vanishing temperature: a
      fingerprint of off-equilibrium dynamics.
AB  - We theoretically study the creep of vortex matter in superconductors. The low
      temperature experimental phenomenology, previously interpreted in terms of
      "quantum tunneling" of vortices, is reproduced by Monte Carlo simulations of a
      purely "classical" vortex model. We demonstrate that a nonzero creep rate in the
      limit of vanishing temperature is to be expected in systems with slow relaxations
      as a consequence of their off-equilibrium evolution in a complex free energy
      landscape.

PMID- 11328180
TI  - Charge density wave, superconductivity, and anomalous metallic behavior in 2D
      transition metal dichalcogenides.
AB  - We propose a theory for quasi-two-dimensional transition metal dichalcogenides
      that provides a unified microscopic picture of the charge density wave (CDW) and
      superconducting phases. We show, based on the electron-phonon coupling and Fermi
      surface topology, that a CDW order parameter with sixfold symmetry and nodes ( f
      wave) gives a consistent description of the available experimental data. The
      elementary excitations in the CDW phase are Dirac electrons. The superconducting
      state has its origin on the attractive interaction mediated by phonons. The
      theory predicts strong deviations from Fermi liquid theory in the CDW phase.

PMID- 11328181
TI  - Field induced biquadratic exchange in hard/soft ferromagnetic bilayers.
AB  - The appearance of biquadratic exchange coupling between soft Fe and hard SmCo
      thin layers is found. The remanent magnetization in the Fe layer reorients from
      parallel to perpendicular with respect to the SmCo easy axis after application of
      large enough negative field. To explain such an unexpected behavior in contacting
      ferromagnetic layers a model is proposed based on Slonczewski's fluctuating
      exchange mechanism. In our samples a partial remagnetization of the hard layer
      creates fluctuations of the bilinear interactions. The intralayer exchange
      averaging of the resulting magnetization fluctuations in the soft layer causes
      the observed biquadratic coupling.

PMID- 11328182
TI  - Spin dynamics in a frustrated magnet.
AB  - 180 degrees spin flips have been identified as the dominant fluctuation mechanism
      at the transverse spin freezing transition in partially frustrated a-Fe92Zr8. The
      form of the selective excitation double Mossbauer spectra, coupled with the
      perfect agreement with zero-field muon spin relaxation data, eliminates other
      relaxation forms.

PMID- 11328183
TI  - Two-stage magnetization reversal in exchange biased bilayers.
AB  - MnF(2)/Fe bilayers exhibit asymmetric magnetization reversal that occurs by
      coherent rotation on one side of the loop and by nucleation and propagation of
      domain walls on the other side of the loop. Here, we show by polarized neutron
      reflectometry, magnetization, and magnetotransport measurements that for samples
      with good crystalline "quality" the rotation is a two-stage process, due to
      coherent rotation to a stable state perpendicular to the cooling field direction.
      The result is remarkably asymmetrically shaped hysteresis loops.

PMID- 11328184
TI  - Strong phonon replicas in be 1s photoemission spectra.
AB  - The Be 1s core level photoemission line from metallic Be is shown to contain
      unexpected internal fine structure. We argue that this fine structure is caused
      by intrinsic excitation of a narrow band of optical phonons in the 1s
      photoemission process. The general importance of the present results for high
      resolution core level photoemission investigations of metals is pointed out.

PMID- 11328185
TI  - Stabilizing distinguishable qubits against spontaneous decay by detected-jump
      correcting quantum codes.
AB  - A new class of error-correcting quantum codes is introduced capable of
      stabilizing qubits against spontaneous decay arising from couplings to
      statistically independent reservoirs. These quantum codes are based on the idea
      of using an embedded quantum code and exploiting the classical information
      available about which qubit has been affected by the environment. They are
      immediately relevant for quantum computation and information processing using
      arrays of trapped ions or nuclear spins. Interesting relations between these
      quantum codes and basic notions of design theory are established.

PMID- 11328186
TI  - Self-organized stable pacemakers near the onset of birhythmicity.
AB  - General amplitude equations are derived for reaction-diffusion systems near the
      soft onset of birhythmicity described by a supercritical pitchfork-Hopf
      bifurcation. Using these equations and applying singular perturbation theory, we
      show that stable autonomous pacemakers represent a generic kind of spatiotemporal
      patterns in such systems. This is verified by numerical simulations, which also
      show the existence of breathing and swinging pacemaker solutions. The drift of
      self-organized pacemakers in media with spatial parameter gradients is
      analytically and numerically investigated.

PMID- 11328187
TI  - Universal learning curves of support vector machines.
AB  - Using methods of statistical physics, we investigate the role of model complexity
      in learning with support vector machines (SVMs), which are an important
      alternative to neural networks. We show the advantages of using SVMs with kernels
      of infinite complexity on noisy target rules, which, in contrast to common
      theoretical beliefs, are found to achieve optimal generalization error although
      the training error does not converge to the generalization error. Moreover, we
      find a universal asymptotics of the learning curves which depend only on the
      target rule but not on the SVM kernel.

PMID- 11328188
TI  - Polymer reptation and nucleosome repositioning.
AB  - We consider how beads can diffuse along a chain that wraps them, without becoming
      displaced from the chain; our proposed mechanism is analogous to the reptation of
      "stored length" in more familiar situations of polymer dynamics. The problem
      arises in the case of globular aggregates of proteins (histones) that are wound
      by DNA in the chromosomes of plants and animals; these beads (nucleosomes) are
      multiply wrapped and yet are able to reposition themselves over long distances,
      while remaining bound by the DNA chain.

PMID- 11328189
TI  - Shape of ecological networks.
AB  - We study the statistics of ecosystems with a variable number of coevolving
      species. The species interact in two ways: by prey-predator relationships and by
      direct competition with similar kinds. The interaction coefficients change slowly
      through successful adaptations and speciations. They are treated as quenched
      random variables. These interactions determine long-term topological features of
      the species network, which are found to agree with those of biological systems.

PMID- 11328190
TI  - Respiratory complications related to bulbar dysfunction in motor neuron disease.
AB  - Bulbar dysfunction resulting from corticobulbar pathway or brainstem neuron
      degeneration is one of the most important clinical problems encountered in motor
      neuron disease (MND) and contributes to various respiratory complications which
      are major causes of morbidity and mortality. Chronic malnutrition as a
      consequence of bulbar muscle weakness may have a considerable bearing on
      respiratory muscle function and survival. Abnormalities of the control and
      strength of the laryngeal and pharyngeal muscles may cause upper airway
      obstruction increasing resistance to airflow. Bulbar muscle weakness prevents
      adequate peak cough flows to clear airway debris. Dysphagia can lead to
      aspiration of microorganisms, food and liquids and hence pneumonia. MND patients
      with bulbar involvement commonly display an abnormal respiratory pattern during
      swallow characterized by inspiration after swallow, prolonged swallow apnoea and
      multiple swallows per bolus. Volitional respiratory function tests such as forced
      vital capacity can be inaccurate in patients with bulbofacial weakness and/or
      impaired volitional respiratory control. Bulbar muscle weakness with abundant
      secretions may increase the risk of aspiration and make successful non-invasive
      assisted ventilation more difficult. We conclude that an evaluation of bulbar
      dysfunction is an essential element in the assessment of respiratory dysfunction
      in MND.

PMID- 11328191
TI  - Prevalence of multiple sclerosis in Vasterbotten County in northern Sweden.
AB  - OBJECTIVE: To estimate the prevalence and clinical characteristics of multiple
      sclerosis (MS) in Vasterbotten County in northern Sweden. METHODS: Individuals
      with MS were identified from several sources. A follow-up interview and/or
      examination was performed in 94% of cases still living in the area during 1997
      99. Onset adjusted prevalence and a definition of onset symptoms were applied.
      RESULTS: A total of 313 cases were identified, resulting in an onset adjusted
      crude prevalence of MS for January 1990 of 125/105 (95% confidence interval (CI):
      112-140). Female predominance was evident (163/105 (95% CI: 142-187) vs 86/105
      (95% CI: 71-104)). Diagnostic coding registers were the most important source for
      identification of cases. CONCLUSIONS: The crude prevalence of MS in Vasterbotten
      was higher than previous reports from other major areas in Scandinavia. The
      adjusted prevalence was significantly higher when compared with a previous study
      from Goteborg, south-western Sweden. The methodology used in this study gives a
      high degree of case ascertainment and increases the comparability of multiple
      sclerosis epidemiological studies.

PMID- 11328192
TI  - Chronic epilepsy with complex partial seizures is not always medically
      intractable--a long-term observational study.
AB  - OBJECTIVE: To study the prognosis of patients with complex partial seizures (CPS)
      with or without simple partial (SPS) and secondarily generalized tonic-clonic
      seizures (GTCS) and to analyze the factors related to the degree of medical
      responsiveness. MATERIAL AND METHODS: A total of 266 adult patients with CPS were
      included in a hospital based observational survey with a follow-up of 2 to 25
      years. Clinical characteristics, seizure frequency, electroencephalography (EEG),
      cerebral computed tomography (CCT) and magnetic resonance imaging (MRI) findings
      were analyzed. Patients were categorized according to their degree of medical
      responsiveness into one of three groups: seizure free, improved control (>50%
      seizure reduction) and poor control. RESULTS: Mean age at follow-up was 44.7
      years (SD 14.7, range 19-93). Mean age at seizure onset was 18.1 years (SD 14.7,
      median 15, range 1-79). Complete seizure control was achieved in 40%, improved
      seizure control in 36% and poor seizure control in 24%. Patients entered
      remission after a mean period of 15.7 years (SD 12.6, median 13, range 1-54) of
      active epilepsy. A third of all seizure-free patients were still in remission 6.1
      years (SD 5.3, median 3.5, range 1-18) after discontinuation of antiepileptic
      drugs (AED). Patients with poor seizure control had a significantly younger age
      at onset (P<0.01), a higher initial seizure frequency (more than 3 per month)
      (P<0.01), abnormal neurological examination (P<0.01), and were more often
      mentally handicapped (P<0.01). Multiple logistic regression analysis revealed a
      high initial seizure frequency, mental handicap and an abnormal neurological
      examination as independent risk factors for poor seizure control. A positive
      family history, a history of febrile convulsions and/or psychosis, an abnormal
      EEG or MRI was not predictive of poor outcome. CONCLUSIONS: Not all patients with
      CPS were medically intractable. Seizure remission can be achieved after a long
      time of active epilepsy. Poor seizure control was associated with a high initial
      seizure frequency, mental handicap and abnormal neurological examination.

PMID- 11328193
TI  - Losigamone add-on therapy in partial epilepsy: a placebo-controlled study.
AB  - OBJECTIVES: To evaluate the efficacy and tolerability of losigamone (LSG).
      PATIENTS AND METHODS: Double-blind, placebo-controlled add-on study with 3x500 mg
      LSG/die for the treatment of chronic partial seizures in 203 patients (99 treated
      with LSG, 104 on placebo). RESULTS: The median percent change of seizures was
      14.9% (LSG) versus 6.7% (placebo) (P=0.004). Seizure frequency was decreased by
      more than 50% in 22.3% (LSG) and 14.6% (placebo) of patients (P=0.13). Mean
      percent change of seizures was best in patients with only one additional
      anticonvulsant drug (LSG versus placebo, P=0.004). Adverse events (usually CNS
      related side effects of mild to moderate intensity) were reported in 59.6% (LSG)
      and 37.5% (placebo) of patients. CONCLUSIONS: LSG proved to be an effective and
      well tolerated anticonvulsant drug for the treatment of chronic partial seizures.

PMID- 11328194
TI  - Video-EEG monitoring in patients with hippocampal atrophy.
AB  - OBJECTIVES: To analyze the value of ictal EEG recordings in patients with
      unilateral magnetic resonance imaging (MRI)-identified hippocampal atrophy and
      concordant interictal epileptiform discharges (IEDs). MATERIAL AND METHODS: The
      ictal EEG patterns in 84 patients with pharmaco resistant epilepsy undergoing an
      anterior temporal lobectomy between 1992 and 1995 were reviewed. The concordance
      between the ictal EEG and MRI and the IEDs was examined. RESULTS: Two-hundred-and
      thirty seizures (76.4%) were concordant and 11 seizures (3.7%) were discordant
      with the atrophic temporal lobe. Sixty seizures (19.9%) were indeterminate in
      localization. Sixty-three of the 69 patients (91.3%) with confirmatory and 14 of
      the 15 patients (93%) with non-confirmatory ictal EEG recordings, respectively,
      experienced an excellent operative outcome (P=0.629, Fisher's exact test).
      CONCLUSIONS: Patients with unilateral hippocampal atrophy and concordant IEDs are
      excellent surgical candidates even when video-EEG monitoring shows discordant or
      non-localizing seizures.

PMID- 11328195
TI  - Education of referring doctors about sudden onset headache in subarachnoid
      hemorrhage. A prospective study.
AB  - OBJECTIVES: Forty percent of patients with aneurysmal subarachnoid hemorrhage
      have prodromal warning episodes and difficulties in identifying these events are
      repeatedly documented. Modifications of diagnostic and referral patterns through
      educational programs of local doctors may help to identify such patients before a
      major devastating rupture occurs. MATERIALS AND METHODS: A teaching program about
      sudden onset headache, targeting referring doctors, was systematically applied
      and its impact on early misdiagnosis of ruptured aneurysms was prospectively
      studied. RESULTS: Forty percent of all studied patients experienced a warning
      episode, manifested as apoplectic headache, prior to hospitalization. An initial
      diagnostic error was evident in 12% of the patients. Diagnostic errors were
      reduced by 77% as a result of continuous interaction between neurosurgeons and
      local physicians. CONCLUSION: Misdiagnosed warning episodes cause greater loss of
      lives and higher morbidity on a population basis than does delayed ischemic
      complications from vasospasm in aneurysmal SAH. Teaching programs focused on
      local physicians have a profound impact on outcome at low cost.

PMID- 11328196
TI  - Education and cognitive decline in Parkinson's disease: a study of 102 patients.
AB  - OBJECTIVE: To understand the correlation between low education level (EL) and the
      cognitive impairment in Parkinson's disease (PD). PATIENTS AND METHODS: This is a
      cross-sectional study of cognitive function in 102 non-demented PD patients, from
      a special clinic (behavioral neurology) in a referral medical center. PD patients
      were divided into low, middle and high EL groups. We used the Chinese version of
      the Cognitive Ability Screening Instrument as a neuropsychological test, which
      covers nine domains of cognitive function. A full score is 100. When determining
      the abnormality rate of each item of CASI, we used age/education stratified
      normal control groups as reference to obliterate the influence of education and
      age on cognitive decline. RESULTS: Recent memory, language and attention are the
      three items in which there were differences between the groups, in terms of
      abnormal performance rates. The high EL group is at less risk of recent memory
      impairment, but at more risk of impairment in language and attention. The other
      six items and total score showed no differences among the groups. Thirty-eight
      percent of the patients had a total score below 1.5 SD of the means of the
      general population. CONCLUSION: This study shows that high EL exerts no
      protective effect on the cognitive decline in PD patients in general, except in
      recent memory. The rate of cognitive dysfunction in PD patients is high. This
      deserves more attention.

PMID- 11328197
TI  - Enzyme linked immunosorbent assay using recombinant HuD-autoantigen for
      serodiagnosis of paraneoplastic neurological syndromes.
AB  - OBJECTIVES: The aim of this study was to evaluate the suitability of an ELISA
      employing purified recombinant HuD antigen, for detection of specific anti-HuD
      antibodies in sera and cerebrospinal fluid (CSF) from patients with
      paraneoplastic neurological syndromes (PNS). MATERIAL AND METHODS: The cutoff for
      optical density readings was estimated by testing of 145 sera from healthy
      subjects. Sera from 17 patients with paraneoplastic neurological syndromes (PNS)
      and evidence of a clear anti-Hu band pattern in an immunoblot employing human
      cerebellar crude extract as antigen were tested. RESULTS: All 17 sera from
      patients with PNS revealed a clear positive result in the HuD-ELISA,
      demonstrating a sensitivity of 100%. Two out of 150 sera from patients with
      various infectious, autoimmune and neoplastic diseases (excluding PNS) showed a
      borderline result in the HuD-ELISA. This reveals a specificity of more than 98%.
      In addition 10 serum/CSF pairs from patients with anti-Hu-syndrome were adjusted
      to equal IgG concentrations and were tested in parallel in the HuD-ELISA. A
      specific antibody index (AI=ODCSF/ODserum) over 1.5 indicates intrathecal
      antibody synthesis. Six of ten patients revealed an AI >1.5, one was borderline
      (AI=1.5), and three had an AI in the range of 0.9-1.2. There appears to be a
      correlation between elevated AIs (>1.5) and presence of oligoclonal bands in the
      CSF. CONCLUSION: Due to its high specificity and sensitivity the recombinant HuD
      ELISA is a suitable test for detection of anti-HuD antibodies in patients with
      putative PNS. In addition, the HuD-ELISA seems to be appropriate for the
      detection of specific intrathecal HuD-antibody synthesis.

PMID- 11328198
TI  - Interleukin-1beta converting enzyme/Caspase-1 (ICE/Caspase-1) and soluble APO
      1/Fas/CD 95 receptor in amyotrophic lateral sclerosis patients.
AB  - OBJECTIVES: The aim of the study was to investigate the role of ICE/ Caspase-1
      and soluble APO-1/Fas/CD 95 receptor in amyotrophic lateral sclerosis patients.
      MATERIAL AND METHODS: The apoptosis parameters were measured by enzyme-linked
      immunosorbent assay (ELISA) in serum and cerebrospinal fluid from 25 amyotrophic
      lateral sclerosis and 15 control patients. RESULTS: There has been shown a
      significant increase of ICE/Caspase-1 level in serum, and significant decrease of
      this parameter in cerebrospinal fluid from amyotrophic lateral sclerosis
      patients. Soluble APO-1/Fas/CD 95 level in amyotrophic lateral sclerosis patients
      did not differ from the control group. There was no significant correlation
      between clinical status, duration of amyotrophic lateral sclerosis, and levels of
      ICE/Caspase-1 and soluble APO-1/Fas/CD 95. CONCLUSION: Our study suggests that
      ICE/Caspase-1 may play a role in neurodegeneration in ALS. Due to ethical
      difficulties we cannot include patients suffering from progressive neurological
      diseases, who are a more appropriate control group for the amyotrophic lateral
      sclerosis patients. Therefore we are limited in drawing conclusions from the
      research.

PMID- 11328199
TI  - Visual impairment in anti-GQ1b positive Miller Fisher syndrome.
AB  - Autoimmune neuropathies such as the Guillain-Barre syndrome (GBS), the Miller
      Fisher syndrome (MFS), and chronic inflammatory demyelinating neuropathy (CIDP)
      have conventionally been considered diseases exclusively of the peripheral
      nervous system. In the last decades, however, several reports of CNS involvement
      in peripheral neuropathy have challenged this view. We describe a patient with
      anti-GQ1b positive MFS who--apart from the classical features--also presented
      with reversible loss of visual acuity suggesting CNS involvement.

PMID- 11328200
TI  - Clinical diagnosis of multiple system atrophy: level of agreement between Quinn's
      criteria and the consensus conference guidelines.

PMID- 11328201
TI  - Axonal Guillain-Barre syndrome: a critical review.
AB  - Axonal Guillain-Barre Syndrome (GBS) was first described by Feasby et al. in
      1986, challenging the existent notion of GBS being a primarily demyelinating
      disease. The severe course and slow recovery commonly seen in these patients was
      ascribed to axonal degeneration. Other authors challenged this claim on several
      grounds. Amidst these controversies, epidemics of a similar illness were reported
      from China, which were given the acronym AMAN, having exclusive motor involvement
      in contrast to the cases already described in which both motor and sensory
      involvement were present (AMSAN). Pathologically, Wallerian degeneration, minimal
      lymphocytic response, absent demyelination or inflammation and periaxonal
      macrophages are prominent features. Ultrastructural studies have revealed node of
      Ranvier to be the prime target of immune attack. A frequent occurrence of
      antecedent Campylobacter jejuni infection and a strong association between
      elevated titres of IgG GM1 and axonal GBS on a background of preceding C. jejunii
      infection has been observed and molecular mimicry between lipopolysaccharides of
      C. jejuni and neural epitopes has been proposed as a mechanism of injury.
      Clinically axonal variant is similar to AIDP, but a more severe course, with
      frequent respiratory involvement, ventilator dependence and significant residue
      may be seen. Diagnosis is essentially electrophysiological. Treatment is similar
      to AIDP, preferential benefit of either IVIG or plasmapheresis needs to be
      further evaluated. A critical review of existing literature in axonal GBS is
      presented.

PMID- 11328202
TI  - Antecedent symptoms in Guillain-Barre syndrome: an important indicator for
      clinical and serological subgroups.
AB  - OBJECTIVES: To examine whether Guillain-Barre syndrome (GBS) can be classified in
      clinical and immunological subgroups based on the type of prior illness.
      Background - The existence of antecedent symptoms supports the diagnosis of GBS
      in patients who experience acute muscle weakness progression. However, little is
      known about additional meanings of determining antecedent symptoms. MATERIALS AND
      METHODS: Prospective investigation of prior infectious illness in GBS and related
      disorders (n=176). RESULTS: The frequent antecedent symptoms in GBS and related
      disorders were fever (52%), cough (48%), sore throat (39%), nasal discharge
      (30%), and diarrhea (27%). Patients who had sore throats or coughs frequently had
      ophthalmoparesis (respectively P=0.0004, P=0.001) and IgG anti-GQ1b antibody
      (P=0.01, P=0.007). Fever was associated with bulbar palsy (P=0.047) and headache
      with facial palsy (P=0.04). Patients with diarrhea often had anti-ganglioside IgG
      (anti-GM1 [P=0.0006] and anti-GM1b [P=0.008]), IgM (anti-GM1 [P=0.03], anti-GM1b
      [P=0.02], and anti-GalNAc-GD1a [P=0.047]) antibodies and rarely showed
      ophthalmoparesis or bulbar palsy (respectively P=0.02, P=0.04). Diarrhea and
      abdominal pain were closely associated with Campylobacter jejuni serology
      (respectively P<0.0001, P=0.01), whereas other symptoms were not related to
      pathogens such as cytomegalovirus, Epstein-Barr virus, or Mycoplasma pneumoniae.
      CONCLUSIONS: Our comprehensive study showed that GBS preceded by sore throat,
      cough, fever, headache, or diarrhea respectively forms clinical or serological
      subgroups, or both. This association is not necessarily dependent on infection by
      the known trigger pathogens.

PMID- 11328203
TI  - Parental concerns for the child with febrile convulsion: long-term effects of
      educational interventions.
AB  - OBJECTIVE: To evaluate long-term effects of educational interventions on parental
      concerns for children with febrile convulsions (FC). SUBJECTS AND METHODS: 209 FC
      parents were recruited from southern Taiwan, and assigned into program or
      pamphlet groups by their choices. A questionnaire was used to examine the
      parental concerns at 4 time points: prior to the interventions, 3 months, 1 year,
      and 2 years after the interventions. RESULTS: The concern scores were high before
      the interventions. Parents concerned that their child is apt to get a fever, has
      further seizures in the night, that FC results in potential brain damage and is
      life threatening. After interventions the concern scores were significantly lower
      for the program group than for the pamphlet group. The educational program was
      the most significant factor that influenced the change in parental concerns. The
      recurrence of FC did not significantly influence the change in the concern
      trajectory in the program group but showed a significant difference in the
      pamphlet group. CONCLUSION: FC parental concerns decreased as time passed
      particularly in the program group. The educational program was the significant
      factor that influenced the change of concern trajectories, and the recurrent/non
      recurrent factor influenced the change of concern only in pamphlet group. FC
      parental concerns should be assessed, and information given combined with
      emotional support.

PMID- 11328204
TI  - Folate, homocysteine and methionine loading in patients on carbamazepine.
AB  - OBJECTIVES: Some antiepileptic drugs (AEDs) are associated with low levels of
      serum (S-FA) and erythrocyte folate (E-FA) and high levels of plasma total
      homocysteine (p-tHcy). We have explored the concentrations of S-FA, E-FA and p
      tHcy in patients on carbamazepine (CBZ). The methionine loading test was applied
      for better assessment of mildly impaired homocysteine metabolism. MATERIAL AND
      METHODS: The study comprised 42 adult patients on CBZ and 42 matched healthy
      controls. Blood samples were drawn prior to and 6 h post methionine loading (6 h
      PML) (0.1 g/kg body weight). RESULTS: The patients on CBZ had significantly lower
      concentrations of fasting S-FA and E-FA than the controls (P=0.0004, P=0.003,
      respectively). Fasting and 6 h-PML p-tHcy concentrations were significantly
      higher in the patients than in the controls (P=0.03 and P=0.0001, respectively).
      The methionine loading test identified additional patients with
      hyperhomocysteinemia undetected by fasting p-tHcy. CONCLUSION: CBZ therapy may be
      associated with low folate and high p-tHcy levels.

PMID- 11328205
TI  - A study of the relationship between participation in common leisure activities
      and seizure occurrence.
AB  - OBJECTIVE: To investigate whether participation in a structured programme of
      fairly intensive leisure activities increased seizure occurrence. MATERIAL AND
      METHODS: 212 adults with medically-intractable epilepsy were closely monitored
      for seizure occurrence during an "activities day", i.e. a day consisting of
      various structured sessions of leisure pursuits (video game play, reading, word
      puzzles, television, physical exercise), and during other days of relative rest,
      whilst undergoing prolonged video EEG monitoring. RESULTS: The relative risk of
      seizures did not differ significantly during activities days [0.71 (95% CL: 0.38
      to 1.33)] compared with days of relative rest. CONCLUSIONS: These findings fail
      to provide empirical support for the hypothesis that cognitive exertion has an
      adverse effect on seizure control.

PMID- 11328206
TI  - Genetic polymorphisms in older subjects with vascular or Alzheimer's dementia.
AB  - OBJECTIVES: Paraoxonase, angiotensin-converting enzyme (ACE),
      methylenetetrahydrofolate reductase (MTHFR), and apo E gene polymorphisms were
      evaluated in older patients with vascular dementia (VD) or late-onset Alzheimer's
      disease (LOAD). MATERIAL AND METHODS: Sixty patients with VD, 45 patients with
      LOAD, and 54 non-demented controls were compared. RESULTS: No differences in the
      distribution of paraoxonase, ACE, and MTHFR polymorphisms were found. The overall
      frequency of apo E epsilon4 allele was "low"; epsilon4 allele was more frequent
      in LOAD (17.5%) and VD (13.3%) compared with controls (9.2%), but the difference
      was not statistically significant. CONCLUSION: Paraoxonase, ACE, and MTHFR
      polymorphisms were not associated with VD or LOAD; these common polymorphisms
      might have a marginal role in the pathogenesis of dementia in older subjects. In
      spite of a "low" frequency of the apo E epsilon4 allele in our sample, the
      frequency of epsilon4 allele was about double in LOAD compared with controls.

PMID- 11328207
TI  - Normalization of markers for dopamine innervation in striatum of MPTP-lesioned
      miniature pigs with intrastriatal grafts.
AB  - As part of the DaNeX study, the uptake and binding of several positron emitting
      tracers was recorded in brain of healthy Gottingen minipigs, in minipigs with a
      syndrome of parkinsonism due to MPTP intoxication, and in parkinsonian minipigs
      which had received intrastriatal grafts of mesencephalic neurons from fetal pigs.
      The specific binding of [11C]NS 2214 to catecholamine uptake sites was reduced by
      two thirds in striatum of the intoxicated animals, while the rate constant for
      the decarboxylation of [18F]fluorodopa was reduced by 50% in the intoxicated
      animals. Several months after grafting, both pre-synaptic markers of dopamine
      fibres were normal in striatum. Dopamine depletion or grafting were without
      effect on the cerebral perfusion rate, measured with [15O]-water, did not alter
      the rate of oxygen metabolism (CMRO2) in brain, and did not alter the binding
      potential of tracers for dopamine D1 or D2 receptors in pig striatum. However,
      the grafting was associated with a local increase in the binding of [11C]PK
      11195, a tracer for reactive gliosis, suggesting that an immunological reaction
      occurs at the site of graft, which might potentially have reduced the graft
      patency. However, this apparent immunological response did not preclude the re
      establishment of normal [18F]fluorodopa and [11C]NS 2214 uptake in the
      allografted striatum.

PMID- 11328208
TI  - The erythrocyte adhesiveness/aggregation test in the peripheral blood of patients
      with ischemic brain events.
AB  - We adopted a simple slide test and image analysis to determine the state of
      erythrocyte adhesiveness/aggregation in the peripheral blood of 45 patients with
      acute ischemic stroke, 30 with TIA and 27 matched controls. A highly significant
      (P=0.005) difference was noted between patients and controls regarding the degree
      of erythrocyte adhesiveness/aggregation while there was no significant difference
      for both erythrocyte sedimentation rate or fibrinogen concentrations. We suggest
      that our slide test might be a low cost and real time method to detect the
      increased erythrocyte aggregability in the peripheral blood of patients with
      acute ischemic neurological events. These findings might be relevant in view of
      recent studies that suggest a favorable effect of therapeutic interventions
      directed at the improvements of this hemorrheological aspect in individuals with
      ischemic vascular conditions.

PMID- 11328209
TI  - Osteoporosis prevention in myasthenia gravis: a reminder.
AB  - OBJECTIVES: Consensus guidelines for bone management of patients taking
      corticosteroids suggest two main interventions: Dual energy X-ray absorptiometry
      (DEXA) scanning in those taking prednisolone > or =7.5 mg daily for > or =6
      months (repeated every 1-3 years as indicated). Bisphosphonate therapy for those
      taking prednisolone > or =15 mg daily for > or =6 months regardless of DEXA
      result, and also for patients with known or high risk of developing osteoporosis
      (including those aged >65 years). MATERIAL AND METHODS: We audited adherence to
      these guidelines in all adults with myasthenia gravis (MG) attending our
      neurology service. RESULTS: Of 80 patients with MG (47 male, mean age 63.3
      years), 34 (43%) had received corticosteroids for > or =6 months. Eighteen were
      taking prednisolone > or =7.5 mg daily (mean dose 16.6 mg) yet only 4 of these
      (22%) had undergone DEXA scanning. Of the 13 patients meeting the guideline
      criteria to receive bisphosphonate therapy, this was prescribed to only 7 (54%).
      Two others were prescribed vitamin D, 2 a calcium supplement and 2 were receiving
      no prophylaxis. CONCLUSION: In these MG patients the guidelines were followed in
      only a minority. Neurologists need greater awareness of the bone health
      consequences of prescribing long-term corticosteroids.

PMID- 11328210
TI  - A congenital dermal sinus presenting the muscle fasciculation and hypertrophy.
AB  - OBJECTIVE: To report unique and unknown clinical features of muscle fasciculation
      and muscle hypertrophy in a case of congenital dermal sinus. PATIENTS: A 16-year
      old girl presented with continuous fasciculation, often cramp, and hypertrophy of
      the left calf muscle. The radiography showed spina bifida of L4, L5 and S1. MRI
      revealed dermal sinus tract from the skin dimple of the back to the dura mater,
      and connected to the intradural inclusion tumor. At surgery the inclusion tumor
      contained many short hairs, and the cauda equina were severely adherent.
      Microdissection of the tumor and the adhesion was performed. At 2 years after
      surgery fasciculation decreased but continued; however, painful cramps of the
      calf muscle do not occur. CONCLUSIONS: Short hairs of dermoid and the adherence
      might be irritative to the cauda equina. The hyperactivity of the stimulated
      motor neuron may cause the muscle fasciculation leading to hypertrophy of the
      calf muscle.

PMID- 11328211
TI  - Organizations of European Obstetricians and Gynecologists: NFOG, EBCOG, EAGO and
      ENTOG, what do they do and what do they want?

PMID- 11328212
TI  - Safety aspects of laparoscopic hysterectomy.

PMID- 11328213
TI  - Does iron-deficient erythropoiesis in pregnancy influence fetal iron supply?
AB  - BACKGROUND: It was investigated whether the iron status in newborns is negatively
      influenced by iron-deficient erythropoiesis of the mother during pregnancy.
      METHODS: The iron status is characterized by hemoglobin, erythrocyte zinc
      protoporphyrin and serum ferritin values. Iron-deficient erythropoiesis of the
      mother is characterized by erythrocyte zinc protoporphyrin values. Measurement of
      erythrocyte zinc protoporphyrin was performed in 103 non-anemic females within 24
      hours after delivery. The iron status of their newborns was measured in cord
      blood. RESULTS: Erythrocyte zinc protoporphyrin concentrations were normal in 62%
      and elevated in 38% of the females, hence 39 women had iron-deficient
      erythropoiesis. There were no significant differences in mean values of the iron
      status parameters between neonates born to females with iron-deficient
      erythropoiesis and neonates born to females not having iron-deficient
      erythropoiesis. No correlation was found between maternal erythrocyte zinc
      protoporphyrin values and any of the neonatal parameters. CONCLUSION: It is
      concluded that fetal iron supply is not negatively influenced by iron-deficient
      erythropoiesis in the mother.

PMID- 11328214
TI  - The risk of limb deficiencies and other congenital abnormalities in children
      exposed in utero to calcium channel blockers.
AB  - AIM: Calcium channel blockers given to pregnant rats have shown an increased
      prevalence of digital and limb defects and their safety in pregnant women has
      thus been questioned. We examined the risk of malformations following exposure in
      utero to calcium channel blockers. METHOD: We conducted a nationwide case-control
      study based on the Hungarian Case-Control Surveillance of Congenital
      Abnormalities and identified 22,865 cases with congenital abnormalities and
      31,151 population controls during the period 1980-1996. Data on drug exposure
      were obtained from official questionnaires and obligatory prenatal care logbooks.
      RESULTS: Among the cases, 586 mothers (2.6%) had been exposed to calcium channel
      blockers during pregnancy compared with 907 controls (2.4%). The overall
      prevalence ratios for 17 congenital abnormalities varied between 1.1 and 1.4, and
      there was no significant increased risk of limb deficiencies or other congenital
      abnormalities. CONCLUSION: Our data did not indicate an increased prevalence of
      congenital abnormalities in offspring exposed to calcium channel blockers in
      utero.

PMID- 11328215
TI  - Maternal hematological status and risk of low birth weight and preterm delivery
      in Nepal.
AB  - BACKGROUND: Our aim was to investigate associations between maternal
      characteristics, with emphasis on hematological status, and risk of low birth
      weight and preterm delivery among pregnant Nepali women. METHODS: In a case
      control study, 1400 pregnant women attending Patan Hospital, Kathmandu, Nepal for
      antenatal care and delivery in the period 1994 to 1996 were included. Women with
      twin pregnancies (n=15) and those delivering infants with congenital
      malformations (n=13) were excluded from the study. Maternal characteristics
      including hematocrit values were recorded at the first antenatal visit. Main
      outcome measures included birth weight, gestation at delivery, Apgar score, mode
      of delivery, and perinatal death. Linear and logistic regression models were used
      to analyze data. RESULTS: Severe anemia (hematocrit < or =24%) was associated
      with a significantly increased risk of low birth weight (<2500 g) and preterm
      delivery (<37 weeks gestation). High hematocrit values (> or =40%) did not
      increase the risk of low birth weight or preterm delivery. The risk of low Apgar
      score or operative deliveries was significantly increased in women with severe
      anemia in the first trimester. Teenagers, women with short height or low body
      mass index, and those belonging to the ethnic group Brahmins, had significantly
      higher risks of delivering low birth weight infants. CONCLUSIONS: Severe maternal
      anemia, particularly in the first trimester, was significantly associated with
      adverse pregnancy outcome. Low maternal age, height or body mass index also
      increased the risk of low birth weight. Improvements in the nutritional status of
      young Nepali women could contribute to improved health among their infants.

PMID- 11328216
TI  - Peripartum hysterectomy-incidence and maternal morbidity.
AB  - BACKGROUND: The aim of the study was to find the incidence and clinical
      implications of peripartum hysterectomy in our department and to identify women
      at risk to improve treatment before resorting to hysterectomy. MATERIAL AND
      METHODS: In the period 1981-1996, cases with peripartum hysterectomy among a
      total of 70,546 deliveries in our department were identified from three different
      sources. The clinical variables were obtained by review of the maternal records.
      RESULTS: In the study period, 11 cases, representing an incidence of 0.2
      peripartum hysterectomies per 1000 deliveries was found. Eight women had a
      cesarean section and three women had a spontaneous vaginal delivery. Six of the
      patients had previous operation on the uterus. The indication for hysterectomy
      was atony in seven, suspected rupture in two, placenta accreta in one and DIC in
      one woman. The maternal morbidity was substantial as the mean number of
      transfusions given was 15 units (range 7-24), and the mean hospitalization time
      was 15 days (range 11-29). There was no maternal mortality, but one infant died
      due to asphyxia caused by placental abruption. CONCLUSIONS: The incidence of
      peripartum hysterectomy was low, but the condition is serious with significant
      maternal morbidity.

PMID- 11328218
TI  - The effects of severe cystocele on urogynecologic symptoms and findings.
AB  - BACKGROUND: To evaluate the effects of severe cystocele on lower urinary tract
      function. METHODS: Urogynecologic evaluation composed of patient questionnaire,
      urinary diary, pad test, Q-tip test, perineal ultrasonography and cystometry was
      performed on 60 patients with reducible grade III or IV cystocele before and
      after reduction of the prolapsed organs. The data were analyzed by Paired-t and
      Chi-square tests and Pearson's correlation analysis. RESULTS: One-hour pad test
      revealed that 17 (28.3%) of the 60 patients with reducible severe cystocele had
      no demonstrable urinary incontinence, while 26 (43.3%) had mild and 17 (28.3%)
      had moderate or severe incontinence. However, all patients had moderate or severe
      incontinence after reduction with vaginal packing (p<0.001). The vaginal packing
      had no significant effect on the maximum bladder capacity, the intravesical
      pressure at maximum capacity and the frequency of detrusor instability (33.3%).
      Whereas, urine loss after 1-hour pad test, bladder neck mobility, straining Q-tip
      angle and PUVA increased significantly after reduction of the cystocele (p<0.01).
      CONCLUSIONS: As grade III or IV cystocele may mask the presence and severity of
      urinary stress incontinence, preoperative urogynecological evaluation should be
      done after reduction of the cystocele.

PMID- 11328217
TI  - The oxytocin antagonist atosiban versus the beta-agonist terbutaline in the
      treatment of preterm labor. A randomized, double-blind, controlled study.
AB  - OBJECTIVE: To compare the efficacy and safety of atosiban and terbutaline for the
      inhibition of preterm labor. METHODS: Two hundred and forty-nine women diagnosed
      with preterm labor at 23-33 weeks of gestation were enrolled of whom 245 women
      received treatment, 116 with atosiban and 129 with terbutaline. At randomization,
      women were stratified by gestational age (< or =28 weeks and >28 weeks). Atosiban
      (iv bolus dose of 6.75 mg, then 300 microg/min for 3 h and 100 microg/min
      thereafter) and terbutaline (5-20 microg/min) were administered by iv infusion
      for 13-18 h. Re-treatment with study drug or an alternative tocolytic agent was
      allowed. Tocolytic effectiveness was assessed in terms of the number of women
      undelivered after 48 hours and 7 days and efficacy and tolerability in terms of
      the number of women remaining undelivered and not requiring alternative tocolytic
      therapy after 48 hours and 7 days of starting therapy. Safety was assessed in
      terms of maternal side effects and neonatal morbidity. RESULTS: Tocolytic
      effectiveness at 48 hours was 86.1% vs 85.3%; p=0.783, and after 7 days it was
      76.5% vs 67.4%; p=0.067, in the atosiban and terbutaline groups, respectively.
      Tocolytic efficacy and tolerability after 48 hours was 72.2% vs 68.2%; p=0.51 and
      after 7 days was 55.6% vs 43.4%; p=0.08 in the atosiban and terbutaline groups,
      respectively. Overall, there were fewer clinically important adverse events with
      atosiban than with terbutaline. CONCLUSIONS: The efficacy of atosiban in the
      inhibition of preterm labor was shown to be comparable to terbutaline. Atosiban
      had a superior safety profile compared with terbutaline in terms of maternal and
      fetal adverse events, and comparable infant outcomes.

PMID- 11328219
TI  - Effect of vaginal devices on bladder neck mobility in stress incontinent women.
AB  - OBJECTIVE: To evaluate how vaginal continence products affect the bladder neck
      mobility and ability to contract the pelvic floor muscles. MATERIAL AND METHODS:
      Fifteen stress incontinent women with leakage >8 g/24 hours were assessed by a
      questionnaire, 24 hours pad test and vaginal ultrasonography of bladder neck
      position and mobility. The patients were examined without any device, with a
      commercially available device (Conveen Continence Guard, CCG, Coloplast A/S) and
      two new shaped test models (TM I/II). Bladder neck position was measured in
      relation to the midline of the pubic symphysis at rest, Valsalva and squeezing.
      RESULTS: About two-thirds of the women became subjectively continent with the
      device. The mean leakage per 24 hours was reduced 87% (61-96%) with a vaginal
      device. No difference was found between the effect of old and new product.
      Evaluated by ultrasonography, the devices worked by supporting the bladder neck
      and reduced the mobility from 34 degrees to 18 degrees with CCG and to 15 degrees
      with TM. Neither CCG nor TM had any adverse effect on the ability to elevate the
      bladder neck during squeezing. CONCLUSIONS: Vaginal devices are effective in
      alleviating stress incontinence and work by supporting a hypermobile bladder
      neck. The devices had no negative effect on the ability to contract the pelvic
      floor muscles. Ultrasonography is a fast and low invasive method to study effect
      of vaginal devices both in the individual patient and for testing new products.

PMID- 11328220
TI  - Impact of second look laparotomy and secondary cytoreductive surgery at second
      look laparotomy in ovarian cancer patients.
AB  - OBJECTIVE: Currently, no prospective study supports or refutes the value of
      secondary cytoreductive surgery in patients with ovarian cancer. We therefore
      reviewed the surgical data of patients who underwent second-look laparotomy (SLL)
      with or without secondary cytoreductive surgery at our department. METHODS:
      Analysis is based on the data of 179 patients who had FIGO stage II (suboptimally
      staged), stage III or IV ovarian cancer, who received a platinum-based first-line
      chemotherapy, who were clinically considered to be tumor-free or had at least a
      clinically partial response to first-line chemotherapy, and who underwent SLL. In
      patients with macroscopic tumor the diagnostic SLL was followed by a secondary
      cytoreductive surgery in order to remove as much tumor as possible. Patients with
      a positive SLL were given second-line chemotherapy. Survival from SLL until death
      was considered the primary statistical endpoint. RESULTS: In 78 out of 179
      (43.5%) a negative SLL could be confirmed pathologically. Patients with negative
      findings, with microscopic, and macroscopic disease at SLL had a median survival
      of 66.6, 57.2, and 19.0 months, respectively (p=0.0001). In patients who
      underwent a secondary cytoreductive operation and in whom residual tumor was
      none, less than 2 cm, or more than 2 cm, the median survival was 22.9, 17.8, and
      15.5 months, respectively (p=0.325). CONCLUSIONS: The presence of macroscopic
      tumor at SLL is an adverse prognostic factor whereas the role of secondary
      cytoreductive surgery at SLL appears to be limited in the routine management of
      ovarian cancer patients.

PMID- 11328221
TI  - Acupuncture for the treatment of vulvar vestibulitis: a pilot study.
AB  - BACKGROUND: The study was conducted to obtain a preliminary indication of the
      effectiveness of acupuncture in the treatment of vulvar vestibulitis but also to
      obtain information how well the women tolerate the treatment. METHODS: Fourteen
      young women with vulvar vestibulitis according to Friedrich's criteria were
      enrolled in the study and 13 fulfilled the acupuncture treatment a total of 10
      times. For evaluation quality of life (QOL) assessments were made before starting
      the treatment and then at one week and at three months after it was completed.
      RESULTS: The treatment was well tolerated and the QOL measurements were all
      significantly higher after both the last acupuncture and three months later,
      compared to before the treatment was started. CONCLUSION: The results seem
      promising, but a larger controlled randomized study should be carried out before
      the treatment can be recommended for use in clinical practice.

PMID- 11328222
TI  - Medium-term clinical outcome of women with menorrhagia treated by rollerball
      endometrial ablation versus abdominal hysterectomy with conservation of at least
      one ovary.
AB  - BACKGROUND: To compare patients' satisfaction, health related quality of life,
      and sexual function among women who were either treated with rollerball
      endometrial ablation or abdominal hysterectomy with conservation of at least one
      ovary for the treatment of menorrhagia. METHOD: Between March 1992 to June 1997,
      91 women underwent rollerball endometrial ablation and 78 women had abdominal
      hysterectomy with preservation of at least one ovary for the treatment of
      intractable menorrhagia. Each was sent a detailed questionnaire at least 18
      months (range 18-60) after surgery. Case notes were reviewed to collect
      additional data relating to pre-operative management and operative details.
      RESULTS: Of 169 women, 120 (71%) returned a completed questionnaire [80/91 women
      (88%) had ablation and 40/78 women (51%) had hysterectomy]. Non-response analysis
      did not reveal any differences in prognostic characteristics between responders
      and non-responders. The length of hospital stay and time taken to return to
      normal daily activity were significantly less in the ablation group. Pre
      menstrual symptoms improved over time but more so in the hysterectomy group, who
      also rated their improvement in general health higher. Women who had hysterectomy
      were more satisfied (100% versus 79%) and would be more likely to recommend it to
      a friend (100% versus 91%). CONCLUSION: Both procedures are effective for the
      treatment of menorrhagia but hysterectomy is associated with better general
      health and fewer pre-menstrual symptoms. Rollerball ablation is a useful
      alternative with many short term benefits and acceptable satisfaction rate.
      Further work is required to evaluate long term effects.

PMID- 11328223
TI  - Medical abortion at 57 to 63 days' gestation with a lower dose of mifepristone
      and gemeprost. A randomized controlled trial.
AB  - OBJECTIVE: To compare the abortifacient efficacy and side-effects of 200 mg and
      600 mg of mifepristone, followed by gemeprost 1 mg vaginally, at 57 to 63 days'
      gestation. DESIGN: Double-blind, randomized controlled trial. SETTING: Ten
      international centers. SUBJECTS: Eight hundred and ninety-six healthy women
      requesting medical abortion. INTERVENTIONS: Participants were randomly assigned
      to receive a single oral dose of mifepristone of either 200 mg or 600 mg followed
      in 48 h by gemeprost 1 mg vaginally. The allocation sequence was concealed by
      using a central pharmacy, and double masking was maintained throughout the study.
      MAIN OUTCOME MEASURES: Complete abortion rate was the principal outcome measure.
      We also evaluated the incidence of side-effects and time to abort. RESULTS: The
      complete abortion rate with the lower dose of mifepristone was similar to that
      with the higher dose (92.4% vs. 91.7%). The relative risk of failure to achieve a
      complete abortion with the 200 mg dose compared to 600 mg dose was 0.9 (95% CI
      0.6-1.4). The timing of the abortion and the incidence of side-effects were
      comparable in both groups, with the exception of reported nausea at one-week
      follow-up which was reported more frequently by women in the higher-dose group.
      CONCLUSIONS: The 200 mg dose of mifepristone is equally as effective as the 600
      mg dose in the antiprogestogen-prostaglandin regimen for pregnancy termination.
      With vaginal gemeprost, the abortifacient efficacy of the regimen remains high at
      57-63 days' gestation.

PMID- 11328225
TI  - Placenta increta complicating the first trimester abortion.

PMID- 11328224
TI  - Evaluation of an optimal luteal phase support protocol in IVF.
AB  - SUBJECT: Luteal phase support has been shown in the past to be an essential part
      of ovarian stimulation protocols, especially the long protocol. It could be shown
      that hCG is as effective as is progesterone for luteal phase support but hCG is
      accompanied by a higher rate of complications. METHODS: Progesterone can be
      administered in several routes. The oral, intramuscular (i.m.) and vaginal routes
      have been chosen frequently in the past. The oral route is ineffective, since
      progesterone has a low oral bioavailability (<10%), and a high rate of
      metabolites, which may result in side effects such as somnolence etc.
      Intramuscular administration provides very high serum levels of progesterone and
      this route is effective with regard to pregnancy rates. Injection of
      progesterone, however, is painful and cannot be done by the patient herself. The
      vaginal route is also effective, progesterone can be administered by the patient
      herself and progesterone is delivered directly to the uterus, where high levels
      are achieved (first uterine pass effect). RESULTS: Several studies could show, in
      the past, that the vaginal administration of progesterone is effective also with
      regard to the downregulation of uterine contractions. Crinone 8% Vaginal Gel is
      especially designed for vaginal use with a special applicator and has to be
      administered once daily in the morning. It adheres to the vaginal epithelium, and
      leakage of the gel is substantially reduced as compared to other drugs like
      capsules or suppositories. CONCLUSIONS: Since progesterone is as effective as hCG
      for luteal phase support but provides a higher safety with regard to ovarian
      hyperstimulation syndromes, and vaginal progesterone is as effective as
      intramuscular progesterone, vaginal progesterone should be the standard choice
      for luteal phase support. Crinone 8% seems to be the most comfortable way of
      vaginal administration of progesterone for luteal phase support in IVF cycles.

PMID- 11328226
TI  - Conservative treatment of complicated cesarean scar pregnancy.

PMID- 11328227
TI  - Vesicovaginal fistula manifested by pregnancy.

PMID- 11328228
TI  - Fetal compression syndrome caused by myoma in pregnancy: a case report.

PMID- 11328229
TI  - Maternal ascites into the abdomen in a patient with status post adnexectomy and
      uterine rupture.

PMID- 11328230
TI  - Virilization during pregnancy caused by ovarian mucinous cystadenocarcinoma.

PMID- 11328231
TI  - Detection of complex chromosomal rearrangements in a woman with repeated
      spontaneous abortions.

PMID- 11328232
TI  - Feto-maternal hemorrhage after a car accident: a case report.

PMID- 11328233
TI  - Endometrial sarcoidosis manifesting as recurrent serometra in a postmenopausal
      woman.

PMID- 11328235
TI  - Social phobia: illness or illusion?

PMID- 11328236
TI  - The quest for biological correlates of social phobia: an interim assessment.
AB  - OBJECTIVE: The primary goal of this review was to assess critically the
      literature concerning the ongoing search for possible biological correlates of
      social phobia. METHODS: In addition to manual searches, Medline, Current Contents
      and Psych Info databases were searched for relevant publications. RESULTS: On the
      evidence of an extensive body of research, so far biological correlates of social
      phobia remain elusive. Furthermore, the majority of studies reveal by default
      that the neurobiological functioning of social phobics is very much like that of
      normal control subjects. CONCLUSION: The conceptual and methodological
      foundations underpinning the current research programme are discussed critically.
      Its main weaknesses were found to be: lack of theory to guide research and aid
      the interpretation of results, static comparisons between subject groups and
      analysis oblivious to great individual variations. Possibilities of alternative
      approaches to study the neurobiology of social phobia are raised. Among others,
      continuous and situation-specific measurement, subjects used as their own
      controls and neurobiological correlates of clinical improvement following
      psychotherapy are considered.

PMID- 11328237
TI  - Is any female preponderance in depression secondary to a primary female
      preponderance in anxiety disorders?
AB  - OBJECTIVE: National community studies consistently identify higher rates of both
      depressive and anxiety disorders in women. The female preponderance in depression
      could be primary or, alternatively, a sex difference in anxiety could determine
      the differential depression rates. We therefore pursue whether the female
      preponderance in depression is secondary to a female preponderance in anxiety
      disorders in a community sample. METHOD: We analyse relevant data from the
      National Comorbidity Study (NCS) database, examining in particular whether sex
      differences in anxiety (here those meeting criteria for panic disorder,
      agoraphobia without panic disorder, generalized anxiety and social phobia)
      influenced sex differences in the prevalence of both major depression and
      dysthymia. RESULTS: Survival analyses indicated that, for both major depression
      and dysthymia, and within subsamples of those with early onset and late onset
      depression, both female sex and a preceding anxiety disorder made significant
      contributions, with preceding anxiety making the consistently stronger
      contribution of the two. CONCLUSION: A proportion of the female preponderance in
      major depression and dysthymia in the general community appears determined by a
      primary sex difference in anxiety.

PMID- 11328238
TI  - Symptomatic recovery and social functioning in major depression.
AB  - OBJECTIVE: To determine whether social functional recovery precedes, runs in
      parallel with, or lags behind symptomatic recovery from major depressive
      episodes. METHOD: Psychiatric out-patients or in-patients aged 18 years or over,
      diagnosed with unipolar major depressive disorder according to DSM-IV, and who
      had received no antidepressant medication in the preceding 3 months were
      identified at 23 collaborating centres from all over Japan (n=95). They were
      rated with the 17-item Hamilton Rating Scale for Depression (HRSD) and the Global
      Assessment Scale (GAS) monthly, and with the Social Adjustment Scale-Self Report
      (SAS-SR) 6-monthly. Remission was defined as 7 or less on the HRSD and recovery
      as 2 or more consecutive months of remission. RESULTS: The GAS ratings showed
      continuous amelioration from baseline to remission, remission to recovery, and
      after sustained recovery. The same trends were observed for SAS-SR scores.
      CONCLUSION: We can expect further amelioration in social adjustment after
      symptomatic remission and recovery of major depressive episodes.

PMID- 11328239
TI  - Subclinical suspiciousness as a risk factor for depressive episodes.
AB  - OBJECTIVE: Previous studies suggest suspiciousness is associated with an
      increased risk of major depressive episodes in psychotic patients. We tested the
      hypothesis that this relationship would extend to nonpsychotic groups. METHOD:
      Data came from the Epidemiological Catchment Area (ECA) study, a longitudinal
      population-based study conducted at five sites in the United States. Baseline
      clinical and demographic features were used to predict the onset of episodes of
      depression at 1-year follow-up in subjects without psychotic symptoms. RESULTS:
      Subclinical suspiciousness was associated with an increased risk of new episodes
      of depression after accounting for demographic variables. However, three of six
      subclinical delusion-like experiences were also associated with an increased risk
      of depressive episodes. None of the subclinical hallucination-like experiences
      predicted subsequent risk. CONCLUSION: Subclinical suspiciousness appears to
      increase the risk of depression in the general population. Some other delusion
      like experiences may do the same.

PMID- 11328240
TI  - Bright light therapy of subsyndromal seasonal affective disorder in the
      workplace: morning vs. afternoon exposure.
AB  - OBJECTIVE: Bright light therapy in seasonal affective disorder (SAD) has been
      studied extensively. However, little attention has been given to subsyndromal
      seasonal affective disorder (SSAD) or the use of bright light in the workplace.
      Many patients using bright light boxes complain of the inconvenience of use. Much
      of this inconvenience involves the often-recommended early timing of the bright
      light therapy. Patients, who already have difficulty awakening, often have
      difficulty using the bright light therapy soon after awakening before going to
      work. If bright light could be used effectively in the workplace, the treatment
      would be more convenient; the improved convenience would probably improve
      compliance. In this study, we studied the effectiveness of bright light therapy
      in subjects with SSAD in the workplace, comparing morning bright light with
      afternoon bright light. METHOD: Morning and afternoon bright light treatment
      (2500 lux) were compared in 30 subsyndromal seasonal affective disorder patients
      using the bright light therapy in the workplace. Hamilton Depression Ratings and
      subjective measures of mood, energy, alertness and productivity were assessed
      before and after 2 weeks of light therapy. RESULTS: Both morning and evening
      bright light significantly decreased the depression ratings and improved the
      subjective mood, energy, alertness and productivity scores. However, there were
      no significant differences between the two times of administration of the bright
      light treatment. Both bright light treatments were well tolerated. CONCLUSION:
      Bright light given in the workplace improves subjective ratings of mood, energy,
      alertness and productivity in SSAD subjects. Morning and afternoon bright lights
      resulted in similar levels of improvement.

PMID- 11328241
TI  - Major demographic, social and economic factors associated to suicide rates in
      Latvia 1980-98.
AB  - OBJECTIVE: The aim of this study is to analyse the dynamics of suicide rates in
      Latvia 1980-98, when dramatic social and economical changes took place. Special
      attention is given to demographic risk groups and major socioeconomic correlates
      influencing the dynamics of suicide rates. METHOD: Descriptive statistics of
      suicide rates and major social and economical correlates. RESULTS: During 1980-98
      there were rapid swings of suicide rates. The increase was generated mainly by
      males reaching a maximum of 72 per 100 000 population in 1993. The sudden drop in
      gross domestic product, the rapid increase in first-time alcohol psychosis and
      the percentage of people unemployed did not correspond strictly with the dynamics
      of suicide rates. CONCLUSION: Demographic and socioeconomic factors could not
      explain sufficiently the rapid changes in suicide rates in Latvia during the
      years 1980-98; psychological factors also have to be considered.

PMID- 11328242
TI  - Structural brain abnormalities in unselected in-patients with major depression.
AB  - OBJECTIVE: Several studies have indicated an increased frequency of cerebral
      atrophy and white matter lesions in patients with major depression, especially in
      older age groups. METHOD: Forty-four representative in-patients with major
      depression in which neurological disorders were clinically excluded, and 49 age-
      and gender-matched controls were MR scanned. RESULTS: Unexpectedly, two of the
      patients had severe brain pathology which could account for their psychiatric
      symptoms. Analysis of the remaining patients (mean age 42 years) did not reveal
      an increased frequency of cerebral atrophy. The number of white matter lesions
      increased with age to an odds ratio greater than 3 for patients aged 50, but this
      was not statistically significant. CONCLUSION: Brain atrophy and white matter
      lesions did not occur with significantly increased frequency in these relatively
      young unselected depressives, but the finding of severe brain pathology stresses
      the importance of brain imaging in late-onset psychiatric disorders.

PMID- 11328243
TI  - Depression in stroke patients 7 years following stroke.
AB  - OBJECTIVE: To study the frequency of depression in stroke patients many years
      following stroke, most previous studies having concentrated on the first few
      years. METHOD: Participants of a previous study of post-stroke depression (99
      stroke patients and 28 control subjects) were re-examined 7 years later.
      Depression was diagnosed using research diagnostic criteria. The test battery
      comprised the Mini Mental State Examination, the Raven Matrices A+B and Word Pair
      Learning. Subjective experience of changes in memory, concentration, mood,
      irritability and fatigue during the 7-year period was also examined. RESULTS:
      Twenty per cent of the stroke patients fulfilled the criteria for major or minor
      depression compared with 11% of the control subjects. No differences in cognitive
      function were found between depressed and non-depressed stroke patients. The
      stroke patients reported experiencing more lability of mood and irritability
      during the 7-year period following stroke than the control subjects. Depressed
      stroke patients experienced more impairment of concentration and memory function
      than non-depressed stroke patients. CONCLUSION: Affective symptoms are common
      among stroke patients 7 years following stroke.

PMID- 11328244
TI  - Criminality and aggression among psychotic in-patients: frequency and clinical
      correlates.
AB  - OBJECTIVE: Violence is common among patients with psychoses. The aim of the study
      was to examine relations between diagnoses, crimes, demographic variables and
      aggressive behaviour during admission to hospital. METHOD: During 14 months 257
      patients were consecutively referred to a unit with high staff/patient ratio.
      They were assessed for clinical symptoms at admittance and discharge. Also legal
      status, coercive measures, criminality and sentences were examined. RESULTS: Of
      the 257 patients, 38% were found in the police register and 33% had been
      prosecuted. Those patients committed 2525 crimes, including 292 acts of violence.
      Problems during admittance were related more to positive symptoms at admittance
      than to earlier criminality. CONCLUSION: Criminality rate is high among patients
      with functional psychoses. Many patients, especially women, had never been
      evaluated by a forensic psychiatrist. The psychiatric services have to consider
      the importance of preventing psychotic relapses and thereby also preventing
      violence and criminality.

PMID- 11328245
TI  - Suicides are seldom prescribed antidepressants: findings from a prospective
      prescription database in Jamtland county, Sweden, 1985-95.
AB  - OBJECTIVE: This study presents data relating to prospectively monitored treatment
      and post-mortem toxicology of individuals who committed suicide. METHOD: A case
      control study of prospectively monitored pharmacological treatment in suicides
      and controls. Psychiatric records and post-mortem toxicology were also studied.
      RESULTS: Fifty-nine subjects who committed suicide purchased twice the number of
      prescriptions as the 118 controls. Sixteen cases received psychiatric in-patient
      care compared to four of the controls. In the last 3 months prior to suicide, 38
      cases (64%) were dispensed drugs: anxiolytics-hypnotics in 17 cases (29%),
      antipsychotics in six cases (10%) and antidepressants in seven cases (12%). More
      psychiatrists than GPs prescribed antidepressants. About one-third of
      psychotropic drugs were retrieved in post-mortem toxicology. CONCLUSION: There is
      a frequent use of psychotropics and psychiatric care among suicides; however, few
      used antidepressants and complied. Many suicides are still misdiagnosed and are
      not adequately treated.

PMID- 11328246
TI  - Suicide mortality in mental retardation:a 35-year follow-up study.
AB  - OBJECTIVE: We investigated suicide mortality among people with mental retardation
      (MR) over a period of 35 years. METHOD: The nationwide, population-based cohort
      of 2369 people with MR was followed-up from a representative sample of 9.4% of
      the population in Finland in 1962. The standardized mortality ratio of suicides
      was calculated and case studies of all MR suicides based on all available data
      were performed. RESULTS: Women with MR had an equal suicide risk to Finnish women
      in general, while men had only one-third of the population risk. Risk factors for
      suicide were similar to those in the general population. Most suicide victims had
      mild MR and were hospitalized for comorbid mental disorders. Suicide methods were
      passive and alcohol was involved in only one case. CONCLUSION: Suicide mortality
      in MR is significantly lowered among males. Suicide prevention in MR should be
      focused on people with comorbid mental disorders. Problems in adjustment to new
      circumstances need to be recognized. Appropriate and adequate treatment of
      comorbid depression is emphasized.

PMID- 11328247
TI  - Increased libido in a woman treated with fluvoxamine: a case report.
AB  - OBJECTIVE: The aim of this paper is to describe a case of increased libido during
      fluvoxamine therapy. METHOD: Single case report. RESULTS: The patient, a 27-year
      old married Japanese woman with borderline personality disorder, developed an
      increased libido with the administration of fluvoxamine. The increased libido
      disappeared after fluvoxamine was discontinued. CONCLUSION: The present findings
      suggest that fluvoxamine can cause increased libido in some patients.

PMID- 11328249
TI  - A re-visit on seasonal variations in suicides in the Hong Kong Special
      Administrative Region (HKSAR).

PMID- 11328250
TI  - Review article: the management of severe Crohn's disease.
AB  - The treatment of severe and active Crohn's disease is currently based on
      immunosuppression, but also involves the management of nutrition, appropriate
      selection of patients for surgery, and maintenance of remission in the long term.
      Corticosteroids remain the drug of the first choice, particularly in the acute
      setting. However, there is evolving understanding of the role of other
      immunosuppressants and immune modifiers, as major concerns regarding side-effects
      and efficacy of steroids in the medium to long-term drive the search for
      alternatives.

PMID- 11328251
TI  - Review article: current endoscopic therapeutic options in the management of
      variceal bleeding.
AB  - Variceal bleeding is a frequent and life-threatening complication of portal
      hypertension. The first episode of variceal bleeding is not only associated with
      a high mortality, but also with a high recurrence rate in those who survive.
      Therefore, many studies and randomized clinical trials have focused on different
      therapeutic strategies aiming to prevent the first episode of variceal bleeding
      (primary prophylaxis), to control haemorrhage during the acute bleeding episode
      (emergency treatment), and to prevent re-bleeding (secondary prophylaxis). These
      strategies involve pharmacological, endoscopic, surgical, and interventional
      radiological modalities. This review concentrates on the clinical aspects of the
      endoscopic modalities used to treat oesophageal variceal haemorrhage, including
      variceal injection sclerotherapy, variceal band ligation, and the use of tissue
      adhesives (glue) and their substitutes. We also draw conclusions from the
      available literature regarding the use of endoscopic modalities in primary
      prophylaxis, emergency treatment, and secondary prophylaxis of variceal re
      bleeding. The management of gastric varices and variceal bleeding during
      pregnancy is also addressed.

PMID- 11328252
TI  - Review article: erythromycin as a prokinetic agent in infants and children.
AB  - Erythromycin has been used as an antibiotic for more than four decades, but only
      in the last 10 years have other therapeutic benefits of this agent been
      exploited. Animal and human studies have demonstrated a prokinetic effect on the
      gastrointestinal tract at sub-antimicrobial doses (typically a quarter or less of
      the antibiotic dose). A limited number of studies have been performed in children
      to investigate this action. A review of this literature is particularly pertinent
      given the frequency of clinical problems related to gastrointestinal dysmotility
      in children and the limited availability of prokinetic agents in paediatric
      practice, compounded by the recent withdrawal of cisapride. The prokinetic
      effects of erythromycin have been investigated in infants with dysmotility
      associated with prematurity, in low birth-weight infants recovering from
      abdominal surgery, and in older children with a variety of other gastrointestinal
      disorders. Only one randomized placebo-controlled trial has been conducted. All
      except one of these studies have shown a beneficial effect of erythromycin in
      either promoting tolerance of enteral feeds or enhancing a measured index of
      gastrointestinal motility. Erythromycin appears to be equally effective when
      given orally (as ethylsuccinate or estolate) or intravenously (as lactobionate).
      Significantly, no serious adverse effects have been reported in studies in which
      erythromycin has been used for its prokinetic effects, although fatal reactions
      have followed the intravenous administration of erythromycin to neonates in
      antibiotic doses.

PMID- 11328253
TI  - Review article: colon cleansing preparation for gastrointestinal procedures.
AB  - Adequate cleansing is essential for reliable diagnostic and surgical colon
      procedures. Accuracy and safety depend on good preparation. Patient compliance is
      enhanced by simplicity and well-tolerated methods. Several methods are available.
      Diet and cathartic regimens utilize clear liquids or diets designed to leave a
      minimal colonic residue. Laxatives, cathartics and enemas are employed. Gut
      lavage solutions are osmotically balanced electrolyte lavage products. Oral
      sodium phosphate solutions and tablets are available and are attractive because
      of good efficacy with a small volume of administration. For colonoscopy and colon
      surgery preparation, these methods have been proven safe and effective. For
      barium enema X-ray, lavage requires an adjunctive agent such as bisacodyl to
      enhance barium coating. Overall, all regimens are well-tolerated. This review
      discusses the development and clinical experience with various colon cleansing
      regimens.

PMID- 11328254
TI  - A systematic comparison of triple therapies for treatment of Helicobacter pylori
      infection with proton pump inhibitor/ ranitidine bismuth citrate plus
      clarithromycin and either amoxicillin or a nitroimidazole.
AB  - BACKGROUND: Triple therapies with proton pump inhibitor/ranitidine bismuth
      citrate (RBC), clarithromycin (C) and either amoxicillin (A) or a nitroimidazole
      (I) are widely accepted as treatment for Helicobacter pylori infection. However,
      it is not clear which of these antibiotic combinations should be preferred. AIM:
      To evaluate whether there is a difference in efficacy between triple therapies
      with proton pump inhibitor/RBC, clarithromycin and either amoxicillin or a
      nitroimidazole. METHODS: The literature was examined for randomized trials
      comparing proton pump inhibitor/RBC-C-A and proton pump inhibitor/RBC-C-I.
      Studies were grouped according to the type of acid inhibitor used (proton pump
      inhibitor or RBC) and differences between pooled cure rates were calculated.
      RESULTS: Forty-seven studies were identified: seven using RBC, 39 using proton
      pump inhibitor, one using both. RBC-C-I was somewhat superior to RBC-C-A,
      although this difference only reached statistical significance in intention-to
      treat analysis. Overall, proton pump inhibitor-C-I and proton pump inhibitor-C-A
      were equally effective, but in nitroimidazole-susceptible strains, proton pump
      inhibitor-C-I performed better, in nitroimidazole-resistant strains, proton pump
      inhibitor-C-A performed better. No serious side-effects were reported and pooled
      drop-out rates were equal. CONCLUSIONS: In general, proton pump inhibitor-C-I and
      proton pump inhibitor-C-A are equally effective and therefore other factors such
      as local prevalence of resistant strains, cost of therapy and options for second
      line treatment should determine which regimen should be preferred. When using
      RBC, the RBC-C-I combination is somewhat superior to RBC-C-A.

PMID- 11328255
TI  - Effect of an enteric-release formulation of naloxone on intestinal transit in
      volunteers taking codeine.
AB  - INTRODUCTION: Constipation is a common side-effect of opioid therapy; in addition
      to their analgesic effect, opioids reduce intestinal secretion and motility with
      an increase in whole-gut transit time. Naloxone, a specific opioid antagonist,
      reverses these effects but may also cause symptoms of opioid withdrawal in
      patients on long-term therapy. AIM: To use an enteric-release formulation,
      designed to produce a topical effect in the gut, with minimum systemic effects.
      METHODS: Naloxone 10 mg b.d. and codeine 30 mg b.d. were used with identical
      placebo capsules in four sets of studies; 12 male volunteers were given the drugs
      alone and in combination, with a control study involving double placebo, during
      each of four study periods. Whole-gut transit time was calculated and compared
      for each treatment period. RESULTS: Naloxone, both alone and with codeine,
      significantly shortened the mean whole-gut transit time compared with the control
      period, respectively, from 53.1 to 42.1 h (P=0.005) and to 40.7 h (P=0.024).
      Urgency to defecate was reported by two volunteers on naloxone alone and by three
      on combination therapy. CONCLUSIONS: The results show that the naloxone
      formulation counteracts the effect of codeine on intestinal transit, suggesting
      that it may have useful clinical applications.

PMID- 11328256
TI  - Surveillance colonoscopy or chemoprevention with COX-2 inhibitors in average-risk
      post-polypectomy patients: a decision analysis.
AB  - OBJECTIVES: Clinical trials are currently underway evaluating the efficacy of COX
      2 inhibitors in decreasing the incidence of adenomas and colorectal carcinoma in
      'average' risk individuals. AIM: To use decision analysis to compare the cost
      effectiveness of celecoxib to surveillance colonoscopy in 'average' risk patients
      who had undergone prior adenoma resection. METHODS: A model of the natural
      history of adenomas after endoscopic polypectomy was constructed using
      probabilities from the literature. Cost estimates were obtained from available
      Medicare reimbursement rates and supplemented by the literature. Three strategies
      were evaluated: (i) no surveillance; (ii) colonoscopic surveillance; and (iii)
      celecoxib chemoprevention. We compared total costs and performed cost
      effectiveness analysis between these strategies. The outcome measures were years
      of life saved and 'high-grade' adenoma prevented. Sensitivity analyses were
      performed on selected variables. RESULTS: Our base-case analysis assumed a 50%
      risk reduction in the incidence of adenomas among patients using celecoxib. No
      surveillance was associated with a cost of $1014 per patient, and colonoscopic
      surveillance with a cost of $1572 per patient, whereas celecoxib use was
      associated with a total cost of $11,503. Ten years after the index colonoscopy,
      15% of patients in the no surveillance strategy developed 'high-grade' lesions
      compared to 13% of patients in the colonoscopic surveillance group and 6% in the
      celecoxib group. There was a small gain in years of life saved (0.006) favouring
      celecoxib over colonoscopic surveillance. The incremental cost-effectiveness
      ratio of celecoxib vs. colonoscopy was $141 871 per 'high-grade' adenoma
      prevented and $1,715,199 per year of life saved. The most important variables in
      determining the cost-effectiveness of celecoxib were its cost and its efficacy.
      CONCLUSION: Chemoprevention with COX-2 inhibitors in 'average-risk'
      postpolypectomy patients is a more expensive strategy compared to colonoscopic
      surveillance.

PMID- 11328257
TI  - Enhanced mucosal fibrinolytic activity in gastroduodenal ulcer haemorrhage and
      the beneficial effect of acid suppression.
AB  - BACKGROUND: The high mortality rate in patients with upper gastrointestinal
      bleeding appears to be particularly related to re-bleeding. The haemostatic
      mechanisms that may influence the re-bleeding of ulcers are largely unknown. AIM:
      We studied and analysed fibrinolytic activity in bleeding ulcer patients and the
      effect of acid suppression on this activity. METHODS: Fibrinolytic activity was
      analysed in mucosal biopsies from 29 bleeding gastroduodenal ulcer patients and
      six controls. We analysed levels of D-Dimer, fibrin plate lysis area, plasminogen
      activator activity, plasminogen activator inhibitor activity, and plasmin
      antiplasmin complexes. RESULTS: Significantly more fibrinolytic activity was
      detected in biopsies from patients with bleeding ulcers compared to controls.
      Moreover, in patients with endoscopic stigmata of recent haemorrhage, mucosal
      fibrinolytic activity was higher compared to patients without stigmata of recent
      haemorrhage. In mucosal biopsies of patients that had used acid suppression
      before admission, a decreased fibrinolytic activity was found compared to
      patients without such therapy. This effect of acid suppression on fibrinolytic
      activity was confirmed in nine patients before and after a 24-h ranitidine
      infusion. CONCLUSIONS: Fibrinolytic activity is enhanced in patients with
      bleeding gastroduodenal ulcers. Acid suppressive therapy decreases this increased
      activity, which may be one of the mechanisms explaining the potential beneficial
      effect of this therapy.

PMID- 11328258
TI  - Control of intragastric pH with omeprazole 20 mg, omeprazole 40 mg and
      lansoprazole 30 mg.
AB  - BACKGROUND: Single daily doses of proton pump inhibitors, omeprazole and
      lansoprazole provide effective acid suppression and equal healing and symptom
      relief in patients with GERD. Despite this, controversy exists as to the efficacy
      of available proton pump inhibitors in the control of gastric acidity. AIM: To
      assess the efficacy of omeprazole 20 mg vs. lansoprazole 30 mg and omeprazole 40
      mg vs. lansoprazole 30 mg in intragastric pH control. METHODS: Study I: 12
      Helicobacter pylori-negative volunteers (mean age 33 years) were treated with
      omeprazole 20 mg and lansoprazole 30 mg in random order before breakfast for 7
      days. Study II: 24 subjects (mean age 36 years) were similarly treated with
      omeprazole 40 mg and lansoprazole 30 mg for 7 days after a baseline pH study. One
      week washout was allowed between studies. Subjects had the same meal on each
      study day. On day seven, a 24-h intragastric pH study was performed. The
      percentage time for which gastric pH > 4 was analysed (Gastrosoft, Synectics
      Medical Inc.) and expressed as mean +/- s.d. RESULTS: (1) Omeprazole 20 mg and
      lansoprazole 30 mg showed no significant difference in the percentage time for
      which gastric pH > 4 in the daytime and night-time periods. (2) The percentage
      time for which pH > 4 with omeprazole 40 mg was significantly greater than
      lansoprazole 30 mg in both daytime (61 +/- 19% vs. 48 +/- 14%, P < 0.001), and
      night-time periods (34 +/- 21% vs. 26 +/- 14%, P < 0.05). (3) A large inter
      subject variation existed in both studies. (4) In 10 subjects who participated in
      both studies, omeprazole 40 mg showed a significantly higher percentage time for
      which pH > 4 in the daytime (69 +/- 18% vs. 51 +/- 15%, P=0.015) than omeprazole
      20 mg. CONCLUSION: These pH data support the therapeutic equivalency of FDA
      approved doses of omeprazole and lansoprazole.

PMID- 11328259
TI  - Colonic motility in chronic ulcerative proctosigmoiditis and the effects of
      nicotine on colonic motility in patients and healthy subjects.
AB  - BACKGROUND: Nicotine decreases diarrhoea and pain in ulcerative colitis without
      reducing inflammation. AIMS: (i) To evaluate the effect of ulcerative
      proctosigmoiditis on motor functions of an uninflamed segment of descending
      colon; and (ii) to assess nicotine's effects on colonic motor functions in
      patients and healthy subjects. METHODS: In healthy subjects (n=30) and patients
      with ulcerative colitis (13; 11 active, two quiescent colitis), we studied the
      effects of intravenous nicotine on colonic transit of solid residue by
      scintigraphy (healthy subjects) and on colonic motility in healthy subjects and
      11 patients. RESULTS: In ulcerative colitis, fasting colonic motility was
      increased, whereas motor response to a meal was significantly reduced; compliance
      was unchanged. In healthy subjects, high-dose nicotine induced transient high
      amplitude propagated contractions and relaxation of the descending colon followed
      by decreased phasic contractions. This dose also accelerated colonic transit. Low
      dose nicotine (mimicking a transdermal nicotine patch) reduced colonic compliance
      in healthy subjects, but did not affect motor function in ulcerative colitis.
      CONCLUSIONS: Ulcerative proctosigmoiditis increases fasting colonic motility and
      reduces tone response to a meal in the descending colon without affecting colonic
      compliance, suggesting changes in physiological responses but not intrinsic wall
      properties. Nicotine has dose-dependent effects on colonic motor activity in
      healthy subjects.

PMID- 11328260
TI  - In-vitro cyclosporin sensitivity of proliferating lymphocytes is predictive of in
      vivo therapeutic response in ulcerative colitis.
AB  - BACKGROUND: The efficacy of cyclosporin in the management of ulcerative colitis
      is recognized. Not all patients respond to this treatment. Existing clinical and
      laboratory parameters are of little use in identifying those most likely to
      respond. AIMS: To determine whether in-vitro sensitivity to cyclosporin as
      measured by a lymphocyte proliferation assay is predictive of in-vivo response to
      therapy. METHODS: The study comprised seven responders with ulcerative colitis,
      seven non-responders, and 14 healthy matched controls. A lymphocyte proliferation
      assay was carried out in the presence of a range of concentrations of cyclosporin
      and a dose-response curve constructed for each subject. The IC(50) value, the
      concentration of cyclosporin that resulted in 50% inhibition of proliferation,
      was calculated for each subject. IC(50) values for responders, non-responders and
      controls were compared using a Mann-Whitney test. RESULTS: There was a wide range
      of values obtained for the study group as a whole. IC(50) values for non
      responders were significantly higher than those of responders (P < 0.05).
      CONCLUSIONS: There is a population-wide variation of in-vitro sensitivity to
      cyclosporin. This is reflected in in-vivo sensitivity as measured by clinical
      response to cyclosporin treatment. Future therapeutic strategies need to address
      this inherent variability of individual response to therapy.

PMID- 11328261
TI  - A randomized controlled crossover study comparing synthetic porcine and human
      secretins with biologically derived porcine secretin to diagnose Zollinger
      Ellison Syndrome.
AB  - BACKGROUND: Although biologically-derived porcine secretin is approved for the
      diagnosis of Zollinger-Ellison Syndrome, it is no longer available in the United
      States. Pure human and porcine secretins have now been synthesized and new drug
      applications have been filed with the Federal Drug Administration (FDA). METHODS:
      In the current study we compared secretin testing results in six confirmed
      Zollinger-Ellison Syndrome patients using the biologically-derived product and
      both synthetic products (human and porcine) in a three-way, randomized, single
      blind Latin-squares crossover study. RESULTS: Using the FDA-approved criterion
      for positive secretin testing (i.e. a serum gastrin concentration increase of >
      110 pg/mL), there was complete agreement between all three agents for all
      patients. With the more stringent NIH criterion (i.e. a serum gastrin
      concentration increase of > 200 pg/mL), positive results persisted in five out of
      six, six out of six and four out of six patients using biologically-derived
      secretin, synthetic porcine secretin, and synthetic human secretin, respectively
      (six out of six, six out of six and four out of six if a positive test was
      defined as a 50% increase in serum gastrin concentration). The time to peak serum
      gastrin concentration after secretin injection occurred within 15 min in all
      studies (in 94% by 10 min and in 77% by 5 min). Three-way comparisons of serum
      gastrin concentrations showed a single statistically significant difference (the
      change from baseline at 15 min between synthetic human and synthetic porcine
      secretin, P=0.0274). Statistically significant changes from baseline occurred at
      1, 2 and 5 min for biologically-derived porcine secretin and at 2 and 5 min for
      both synthetic porcine and synthetic human secretin, in keeping with the expected
      time curve for positive tests. All three agents were well-tolerated. CONCLUSIONS:
      These data suggest that either synthetic secretin product, when released onto the
      United States market, can be used to confirm Zollinger-Ellison Syndrome.

PMID- 11328263
TI  - Effect of interferon therapy on the development of hepatocellular carcinoma in
      patients with hepatitis C virus-related cirrhosis: a meta-analysis.
AB  - BACKGROUND: The role of interferon in the prevention of hepatocellular carcinoma
      remains controversial. AIM: In this meta-analysis we evaluated the hepatocellular
      carcinoma incidence in interferon-treated and -untreated patients with hepatitis
      C virus-related cirrhosis. METHODS: Eleven studies with 2178 patients were found
      to fulfil our inclusion criteria. The pooled odds ratio (OR) and 95% confidence
      intervals (CI) were calculated from the raw study data. RESULTS: Hepatocellular
      carcinoma development was significantly more frequent in untreated (21.5%) than
      in interferon-treated patients (8.2%; OR: 3.0, 95% CI: 2.3-3.9). In the five
      studies reporting hepatocellular carcinoma incidence in patients with and without
      sustained response to interferon, hepatocellular carcinoma was detected at a much
      higher rate in patients without (9%) than with a sustained response (0.9%; OR:
      3.7, 95% CI: 1.7-7.8). Moreover, hepatocellular carcinoma developed significantly
      more frequently in the untreated patients than in the non-sustained responders
      (OR: 2.7, 95% CI: 1.9-3.9). The benefit from interferon on hepatocellular
      carcinoma incidence was not influenced by the study type (prospective or
      retrospective), the follow-up duration, or the study origin. CONCLUSIONS:
      Interferon therapy significantly reduces the hepatocellular carcinoma risk in
      patients with hepatitis C virus cirrhosis. Hepatocellular carcinoma development
      becomes almost negligible among sustained responders, but a reduction in
      hepatocellular carcinoma incidence is also achieved even in the non-sustained
      responders.

PMID- 11328262
TI  - Role of reactive oxygen metabolites in aspirin-induced gastric damage in humans:
      gastroprotection by vitamin C.
AB  - BACKGROUND: The roles of active oxygen metabolites and anti-oxidative defenses in
      aspirin (ASA)-induced gastric damage have been little studied. AIM: We determined
      the effects of aspirin (400 mg b.d.) with or without vitamin C (480 mg b.d.) for
      3 days on gastric mucosa in human volunteers. METHODS: Gastric injury was
      assessed endoscopically; gastric blood flow, reactive oxygen release (quantified
      by chemiluminescence), lipid peroxidation, myeloperoxidase, superoxide dismutase
      and glutathione peroxidase activity and intragastric vitamin C content were
      measured. Expression of superoxide dismutase and glutathione peroxidase mRNAs was
      assayed semi-quantitatively. RESULTS: ASA produced erosions, a marked increase in
      chemiluminescence, lipid peroxidation, and myeloperoxidase activity. It also
      resulted in a suppression of gastric blood flow, intragastric vitamin C levels,
      superoxide dismutase and glutathione peroxidase activities. The addition of
      vitamin C significantly attenuated gastric damage and reversed the effects of ASA
      on these parameters. Superoxide dismutase and glutathione peroxidase mRNAs were
      decreased in ASA-treated subjects; the addition of vitamin C restored their
      regular levels. CONCLUSIONS: (i) free radical-induced lipid peroxidation and
      suppression of antioxidizing enzymes play an important role in gastric damage
      induced by aspirin; (ii) increased myeloperoxidase activity suggests activated
      neutrophils to be the major source of these radicals; (iii) vitamin C protects
      against ASA-induced damage due to its anti-oxidizing activity.

PMID- 11328264
TI  - Rapid detection of anti-Helicobacter pylori IgG in urine using
      immunochromatography.
AB  - BACKGROUND: Non-invasive methods to detect the presence of H. pylori infection
      continue to be refined. AIM: To evaluate a new 20-min immunochromatography method
      (RAPIRUN H. pylori Antibody) for the presence of anti-H. pylori IgG in urine.
      METHODS: We used the (13)C-urea breath test to establish H. pylori status. We
      evaluated the urine test among 104 subjects including 43 with H. pylori infection
      confirmed by repeatedly positive urea breath tests and 61 H. pylori-negative
      subjects with repeatedly negative urea breath tests. Forty-one of the 43 subjects
      with H. pylori infection had a positive rapid urine test with two false negative
      tests. There were two false positive tests among the 61 with repeatedly negative
      urea breath tests. The sensitivity, specificity, positive and negative predictive
      values for the rapid urine test were 95.3%, 96.7%, 95.3%, and 96.7%,
      respectively. The kit was easy to use and required no special equipment.
      CONCLUSIONS: The rapid immunochromatography method for determination of anti-H.
      pylori IgG proved to be reliable with excellent sensitivity and specificity and
      is likely to be useful for both clinical and epidemiological studies.

PMID- 11328265
TI  - Evaluation of five commercial serological tests for the detection of Helicobacter
      pylori infection in Chinese.
AB  - BACKGROUND: Commercial serological tests for the detection of Helicobacter pylori
      infection must be locally validated. We evaluated the accuracy of five commercial
      tests in the Chinese population. METHODS: Serum samples were collected from
      patients referred for upper endoscopy. Antral biopsies were taken for
      histological examination and culture of H. pylori. The gold standard for
      diagnosing H. pylori infection was positive histological staining and/or positive
      H. pylori culture. The serum samples were tested for H. pylori antibodies using
      the following tests: (i) Cobas Core Anti-H. pylori EIA; (ii) GAP IgG; (iii) GAP
      IgM; (iv) H. pylori microwell EIA (Quidel); and (v) Premier H. pylori. The
      sensitivity, specificity and accuracy of each test was calculated according to
      the manufacturers' instructions or according to a new cut-off value. RESULTS: A
      total of 158 patients were recruited amongst whom 114 (72%) were H. pylori
      positive. Indeterminate results varied from 7% to 19%. The accuracy of the tests
      varied from 57% to 85%. By using new cut-off values, the accuracy was much
      improved, ranging from 73.4% to 86.7%. CONCLUSIONS: By defining new cut-off
      values for the Chinese population, we were able to improve the performance of
      some of the serology tests. This illustrates the importance of local validation.

PMID- 11328266
TI  - Impact of Helicobacter pylori resistance to clarithromycin on the efficacy of the
      omeprazole-amoxicillin-clarithromycin therapy.
AB  - BACKGROUND: Helicobacter pylori resistance to clarithromycin is relatively
      frequent in France and is assumed to be the main cause of failure of the proton
      pump inhibitor-amoxicillin-clarithromycin (proton pump inhibitor-AC) therapy,
      which is the first-line regimen in France. AIM: To determine the respective
      effects of clarithromycin primary and secondary resistances on efficacy of the
      proton pump inhibitor-AC regimen and to determine whether failures are associated
      with persistence of the same strain or with emergence of a new one. METHODS: A
      total of 123 H. pylori-infected patients were treated for 7 days with omeprazole
      20 mg b.d., amoxicillin 1 g b.d., and clarithromycin 500 mg b.d. Eradication was
      assessed by breath test in 102 patients. Minimal inhibitory concentrations of
      clarithromycin were determined by E-test. Strain genotyping was performed by
      random amplified polymorphic DNA. RESULTS: The pre-treatment and post-treatment
      prevalences of clarithromycin resistance were 19% (23 out of 123) and 69% (nine
      out of 13), respectively. The rates of eradication were 68% (69 out of 102), 79%
      (67 out of 85), and 12% (two out of 17) for all, susceptible and resistant
      strains, respectively. The post-treatment isolate was available for six patients
      with a susceptible pre-treatment isolate and a persistent infection. Resistance
      emerged in two patients and was associated with persistence of the pre-treatment
      strain in one and with selection of a new strain in the other. CONCLUSIONS: In
      our hospital, failures of the proton pump inhibitor-AC therapy are related to
      both clarithromycin primary and secondary resistances, but the emergence of
      secondary resistance does not explain all of the failures in the initial
      clarithromycin-susceptible group. In that group a new strain can emerge after
      failure.

PMID- 11328267
TI  - Polaprezinc attenuates the Helicobacter pylori-induced gastric mucosal leucocyte
      activation in Mongolian gerbils--a study using intravital videomicroscopy.
AB  - BACKGROUND: We previously demonstrated that Helicobacter pylori colonization
      evokes gastric mucosal inflammation and an extensive increase in lipid peroxides
      and glutathione in Mongolian gerbils. Zinc and its derivative, polaprezinc, have
      been reported to be potent antioxidants in gastric mucosa. AIM: To examine the
      effect of polaprezinc on gastric mucosal oxidative inflammation in H. pylori
      colonized Mongolian gerbils. METHODS: Sixty-eight male Mongolian gerbils were
      orally inoculated with H. pylori (ATCC43504, 5 x 10(8) CFUs/gerbil; H. pylori
      group) and 35 gerbils were inoculated with the culture media (control group).
      Twenty-two gerbils in the H. pylori and 13 gerbils in the control group were fed
      with diets containing polaprezinc (0.06%, 100 mg/kg, 10 times the usual clinical
      dose) (H. pylori + polaprezinc group, polaprezinc group). The remaining gerbils
      were fed a standard laboratory chow diet. Neutrophil infiltration, assessed
      histologically and by the activity of myeloperoxidase, the contents of CXC
      chemokine (GRO/CINC-1-like protein) and the contents of thiobarbituric acid
      reactive substances, was evaluated in each group 12 weeks after the inoculation.
      Separately, gastric mucosal leucocyte activation and capillary perfusion were
      also assessed using intravital microscopy 2, 4, 8 and 12 weeks after the
      inoculation. RESULTS: In all H. pylori-inoculated animals, the bacterial
      infection persisted throughout the experimental period. Gastric mucosal lesion
      formation in the H. pylori group was significantly inhibited in the H. pylori +
      polaprezinc group. Elevated levels of myeloperoxidase activity, GRO/CINC-1 and
      thiobarbituric acid-reactive substances in the H. pylori group at 12 weeks were
      attenuated significantly by polaprezinc treatment. Enhanced levels of venular
      leucocyte activation observed in the H. pylori group were attenuated
      significantly in the H. pylori + polaprezinc group during both the early phase (2
      weeks) and late phase (12 weeks). CONCLUSION: Polaprezinc inhibited H. pylori
      associated gastric mucosal oxidative inflammation, including initial micro
      vascular leucocyte activation, in Mongolian gerbils.

PMID- 11328268
TI  - H. pylori-gastrin link in malt lymphoma.

PMID- 11328270
TI  - The safety of proton pump inhibitors.

PMID- 11328271
TI  - Images in haematology. Sweet's syndrome after granulocyte colony-stimulating
      factor administration for refractory myelodysplastic syndrome.

PMID- 11328272
TI  - Images in haematology. Erythrophagocytosis.

PMID- 11328273
TI  - The Leukaemia Research Fund/United Kingdom Cancer Cytogenetics Group Karyotype
      Database in acute lymphoblastic leukaemia: a valuable resource for patient
      management.

PMID- 11328274
TI  - Recent advances in the molecular and cellular biology of chronic myeloid
      leukaemia: lessons to be learned from the laboratory.

PMID- 11328275
TI  - Guidelines for the clinical use of red cell transfusions.

PMID- 11328276
TI  - A DNA-based immunization protocol to produce monoclonal antibodies to blood group
      antigens.
AB  - A major challenge facing transfusion medicine is the establishment of
      immunological methods to produce specific and avid blood group typing reagents to
      the many polymorphic blood group antigens. This is especially true when sources
      of human antibody are limited. Based on the knowledge that inoculation with
      plasmid DNA can induce a humoral response in the host animal, we inoculated mice
      with plasmid DNA followed by a single boost injection with plasmid-transfected
      cells that have a high level of expression of the same target protein. Using this
      method, several hybridoma clones that produced strongly reactive antibodies
      specific for the Kell polymorphic antigens (anti-K, anti-k, anti-Kp(a)) were
      isolated. The monoclonal antibodies that were produced with this method have
      potential clinical utility for identifying a patient's blood type and for
      screening for antigen-negative donor blood.

PMID- 11328277
TI  - Residual risk of transfusion in Ghana.
AB  - Plasma samples from replacement and volunteer blood donors in Kumasi, Ghana were
      pooled and tested using a duplex human immunodeficiency virus (HIV) and hepatitis
      C virus (HCV) RNA detection METHOD: Individual plasmas constitutive of reactive
      pools were confirmed using reverse transcription-polymerase chain reaction. HIV
      and HCV infections were significantly higher in 1569 replacement donors than in
      1169 volunteers; 2.4 and 1.7 versus 0.3 and 0.7% respectively (P < 0.01). Two
      duplex RNA-positive plasma pools contained a confirmed/seronegative HIV or HCV
      RNA individual plasma. The residual post-transfusion risk of HIV and HCV
      infection of blood collected from replacement blood donors ranged between 1:260
      and 1:16 393 after screening for anti-HIV, p24 antigen and anti-HCV. These data
      indicate that in high-prevalence HIV and HCV blood donor populations, a
      substantial residual post-transfusion risk of infection remains. This risk might
      be reduced by collecting blood in younger volunteer donors or by genomic
      screening.

PMID- 11328278
TI  - Provision of platelet support for fetuses and neonates affected by severe
      fetomaternal alloimmune thrombocytopenia.
AB  - Severe fetomaternal alloimmune thrombocytopenia requires urgent treatment with
      compatible platelet concentrates. As prompt treatment is sometimes delayed owing
      to the unavailability of compatible platelets, we established an accredited
      platelet donor panel to provide effective and timely transfusion support for
      fetal and neonatal therapy. After a mass screening programme of over 60,000 blood
      donations, 45 HPA-1a-negative donors with no antibodies to HPA, HLA, red cell
      antigens and granulocytes/lymphocytes, and with low titre anti-A and/or -B were
      accredited. All accredited donors were fully genotyped for HPA-1, -2, -3 and -5
      by PCR-SSP. Ninety-one per cent of the accredited donors were also negative for
      HPA-5b.

PMID- 11328279
TI  - Molecular characterization of the PK-LR gene in sixteen pyruvate kinase-deficient
      patients.
AB  - We studied the PK-LR gene in 16 unrelated patients with congenital haemolytic
      anaemia associated with erythrocyte pyruvate kinase deficiency. Fifteen different
      mutations were detected among the 28 mutated alleles identified: two deletions
      (del 1010G, del 1042--1044); one four nucleotide duplication (nt 1515--1518,
      GGTC); one splice site [IVS6(-2)t]; nine missense (991A, 1003A, 1151T, 1160G,
      1181T, 1181A, 1456T, 1483A, 1529A); and two nonsense (721T, 1675T) mutations.
      Eight of them [del 1010G, del 1042--1044, dupl 1515--1518, IVS6(-2)t, 1003A,
      1160G, 1181T, 1181A] were novel. The deletion 1042-1044 causes the loss of Lys
      348. Deletion 1010G and duplication 1515-1518 determine a frameshift and the
      creation of a stop codon at nucleotides 1019 and 1554 respectively. Mutation
      IVS6(-2)t leads to an alteration of the 5' and 3' splice site consensus sequence;
      the cDNA analysis shows a 67-bp deletion in the first part of exon 11 (del 1437-
      1503). All the four new missense mutations involve highly conserved amino acids.
      The most frequent mutation in Italy would appear to be 1456T. Correlation was
      made between mutations, biochemical characteristics of the enzyme and clinical
      course of the disease.

PMID- 11328280
TI  - Erythropoietin synthesis by tumour tissues in a patient with uterine myoma and
      erythrocytosis.
AB  - We report a patient with uterine myoma (leiomyoma) and erythrocytosis in whom
      erythropoietin (Epo) production in the leiomyoma tissue was identified by reverse
      transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent
      assay (ELISA). A 48-year-old Japanese woman with uterine myoma showed marked
      erythrocytosis (haemoglobin: 20.2 g/dl, haematocrit: 61.1%, red blood cells: 6.51
      x 10(12)/1). After hysterectomy, erythrocytosis rapidly disappeared. In the
      leiomyoma tissue collected from the patient, Epo mRNA expression was confirmed
      using RT-PCR. Furthermore, ELISA showed that the Epo protein level was
      significantly increased compared with those in control tissues. It is suggested
      that the pathogenesis of erythrocytosis in patients with uterine myoma involves
      ectopic Epo production by leiomyoma tissues.

PMID- 11328281
TI  - Decreased expression of transcription factor GATA-2 in haematopoietic stem cells
      in patients with aplastic anaemia.
AB  - Aplastic anaemia is characterized by reduced haematopoiesis resulting in
      pancytopenia. It has been speculated that there is an injury in haematopoietic
      stem cells in the bone marrow; however, the precise nature of the injury has not
      been elucidated. In this study, the levels of expression of mRNAs for three
      transcription factors, GATA-2, SCL and AML1, which function in the early stages
      of haematopoiesis, were examined by quantitative polymerase chain reaction in
      patients with aplastic anaemia, idiopathic thrombocytopenic purpura (ITP) and
      normal subjects. Among these factors, expression of GATA-2 mRNA in purified CD34
      positive cells was markedly decreased in aplastic anaemia compared with that in
      ITP and in normal subjects. The expression levels of SCL and AML1 mRNA in CD34
      positive cells in aplastic anaemia were not different from those in normal
      subjects. When the expression of GATA-2 protein in CD34-positive cells was
      examined by immunocytochemical analysis, the percentage of GATA-2-positive cells
      in aplastic anaemia was lower than that in normal subjects. These findings
      strongly suggest that there is an aberrant expression of transcription factors in
      stem cells in aplastic anaemia, which may be responsible for the development of
      the disease.

PMID- 11328282
TI  - The clinical features, risk factors and outcome of thrombotic thrombocytopenic
      purpura occurring after bone marrow transplantation.
AB  - In this study, we retrospectively analysed the clinical features, risk factors
      and outcome of 22 patients with thrombotic thrombocytopenic purpura (TTP)
      occurring after allogeneic stem cell transplantation. All but two of these
      patients received stem cells from unrelated donors (UDs), two-thirds were female,
      three-quarters were adults and leukaemia was the major reason for transplant. The
      incidence of TTP was 20 out of 332 patients (6%) with UD transplants and two out
      of 104 recipients (2%) of matched sibling allografts (P = 0.16). In order to
      ascertain basic demographic risk factors for the development of TTP, we compared
      the 22 patients with 434 patients who did not develop TTP. Compared with patients
      who did not develop TTP, patients with TTP were nearly three times older (P <
      0.001) and were more than twice as likely to be female (P = 0.001). Because > 90%
      of patients were recipients of UD marrow, we then compared the 20 UD-bone marrow
      transplantation (BMT) patients with 60 randomly selected UD-BMT patients who did
      not develop TTP. On univariate analysis, age and female gender were again
      significant risk factors, as was grade II-IV acute graft-versus-host disease
      (GvHD) (P = 0.002), and there was a trend towards an association with chronic
      GvHD (P = 0.083). However, after logistic regression analysis, only age and sex
      remained significant (P < 0.001 and 0.009 respectively). We report an 86%
      mortality with only three survivors out of 22 patients, and one of these remains
      thrombocytopenic and red cell transfusion dependent, possibly in part because of
      graft hypoplasia. Six out of 17 patients responded to plasmapheresis, but the
      majority of them ultimately succumbed because of TTP, often in association with
      GvHD or fungal infection.

PMID- 11328283
TI  - Greater inhibition of platelet procoagulant activity by antibody-derived
      glycoprotein IIb--IIIa inhibitors than by peptide and peptidomimetic inhibitors.
AB  - Antibody-derived GPIIb-IIIa antagonists, such as the c7E3 Fab fragment abciximab,
      have been shown to inhibit platelet procoagulant activity as well as platelet
      aggregation. Whether low-molecular-weight peptide-derived and peptidomimetic
      antagonists also inhibit platelet procoagulant activity in a similar manner has
      not been fully investigated. We compared the effects of the antibody-derived
      antagonists c7E3 Fab and m10E5 IgG, the peptide-derived antagonists eptifibatide,
      MK-852 and RGDS, and the peptidomimetic RO44--9883 on platelet procoagulant
      activity and on the stimulated cytosolic calcium increases that promote
      procoagulant activity. Procoagulant activity was measured as prothrombinase
      activity in gel-filtered platelets, activated by collagen plus thrombin or
      collagen alone, with and without stirring. The stimulated increases in cytosolic
      calcium were measured in parallel samples of platelets loaded with fura-2AM. Both
      c7E3 and m10E5 inhibited prothrombinase activity by 40--50% under all conditions
      of activation tested and inhibited cytosolic calcium increases to a similar
      extent in stirred, but not unstirred, platelets. The low-molecular-weight
      antagonists caused significantly less inhibition of prothrombinase activity in
      collagen plus thrombin-stimulated platelets, and produced no inhibition but
      rather a slight enhancement of activity in platelets stimulated by collagen
      alone. These antagonists also had little or no effect on the cytosolic calcium
      increases in stirred platelets. These differential effects of antibody-derived
      versus non-antibody GPIIb-IIIa antagonists on procoagulant activity may be a
      factor contributing to the differing anti-thrombotic effects of these antagonists
      seen in clinical trials.

PMID- 11328284
TI  - Polymorphonuclear leucocytes mediate endogenous thrombus lysis via a u-PA
      dependent mechanism.
AB  - Many human thrombi lyse spontaneously without the administration of lytic drugs
      and cause no clinical symptoms. The mechanisms by which this occurs are
      incompletely understood. We found that model thrombi prepared from whole human
      blood in a Chandler loop also exhibited significant spontaneous lysis. Lysis was
      inhibited by chemical protease inhibitors, consistent with proteolysis resulting
      primarily from serine proteases, with a small contribution from matrix
      metalloproteinases. Whole blood was fractionated into platelet-rich plasma and
      cell populations. Significant spontaneous lysis was observed in platelet-rich
      thrombi enriched with polymorphonuclear leucocytes (PMNs), whereas mononuclear
      cells (MCs) and erythrocytes did not contribute to lysis. Incorporation of
      antibodies to urokinase (u-PA) and its receptor u-PAR neutralized a large
      proportion of the activity. Incubation of plasma with PMNs generated free u-PA
      activity, which was also detectable in model thrombi and in vivo human thrombi.
      Purified neutrophils, free of eosinophils, generated activity identical to PMNs.
      Smaller contributions to lysis by tissue-type plasminogen activator (t-PA),
      elastase and cathepsin G were also identified. These findings suggest a major
      role for circulating PMNs in endogenous thrombus lysis.

PMID- 11328285
TI  - Haemophilia B mutations in Sweden: a population-based study of mutational
      heterogeneity.
AB  - The present series comprises all families (n = 77) with haemophilia B in Sweden
      and may be considered to be representative for the purposes of a population-based
      study of mutational heterogeneity. The 77 families (38 severe, 10 moderate, 29
      mild) had 51 different mutations in total. Thirteen families had total, partial
      or small deletions, two had mutations in the promoter, eight families had splice
      site mutations, 14 had nonsense and the remaining 41 had missense mutations. Ten
      of the mutations, all C-->T or G-->A, recurred in 1--6 other families. Using
      haplotype analysis of seven polymorphisms in the factor IX (FIX) gene, we found
      that the 77 families carried 65 unique, independent mutations. Of the 48 families
      with severe or moderate haemophilia, 23 (48%) had a sporadic case of haemophilia
      compared with 31 families out of 78 (40%) in the whole series. Five of those 23
      sporadic cases carried de novo mutations, 11 out of 23 of the mothers were proven
      carriers and, in the remaining seven families, it was not possible to determine
      carriership. Eleven of the 48 patients (23%) with severe haemophilia B developed
      inhibitors and all of them had deletions or nonsense mutations. Thus, 11 out of
      37 (30%) patients with severe haemophilia B as a result of deletion/nonsense
      mutations developed inhibitors compared with 0 out of 11 patients with missense
      mutations. The ratio of male to female mutation rates was 5.3 and the overall
      mutation rate was 5.4 x 10(-6) per gamete per generation.

PMID- 11328286
TI  - Clinical spectrum of hepatitis C-related liver disease and response to treatment
      with interferon and ribavirin in haemophilia or von Willebrand disease.
AB  - Our aim was to evaluate the severity of liver disease resulting from chronic
      hepatitis C in haemophilia or von Willebrand disease and the efficacy of 6 months
      treatment with interferon alpha and ribavirin. Fifty-five liver biopsies were
      performed in 43 patients without any bleeding complications, as seen with
      ultrasound immediately after the biopsy and 48 h thereafter. Histological changes
      were mild, with low scores for both inflammation and fibrosis, in spite of long
      exposure to blood products (mean 27 years). Two patients had compensated
      cirrhosis. Thirty-five out of 39 included patients completed study treatment.
      Hepatitis C virus (HCV)-RNA was negative in 77% (30/39) of patients at the end of
      treatment, and 36% (14/39) achieved a complete sustained response at follow-up 6
      months after treatment. Treatment failure was more frequent in patients with
      virus genotype 1 compared with non-1 (P = 0.0003). The response rate correlated
      well with that of non-haemophilic patients. In summary: (1) liver biopsy was safe
      with our regimen; (2) liver disease in our patients was usually mild and had a
      slow progress; (3) only HCV genotype 1 predicted treatment failure; (4) our
      treatment results agreed with those from non-haemophilic patients.

PMID- 11328287
TI  - Activation of coagulation factor XI, without detectable contact activation in
      dengue haemorrhagic fever.
AB  - A prospective cohort study was performed in 50 patients with dengue haemorrhagic
      fever (DHF) to determine the potential role of the contact activation system and
      factor XI activation (intrinsic pathway) in the coagulation disorders in DHF. To
      establish whether TAFI (thrombin-activatable fibrinolysis inhibitor) was involved
      in the severity of the coagulation disorders, the TAFI antigen and activity
      levels were also determined. Markers of contact activation (kallikrein--C1
      inhibitor complexes), the intrinsic pathway of coagulation (factor XIa--C1
      inhibitor complexes) and TAFI were measured and correlated to thrombin generation
      markers (thrombin--anti-thrombin complexes (TAT), prothrombin fragment 1+2
      (F1+2)) and a marker for fibrinolysis [plasmin--alpha 2--anti-plasmin complexes
      (PAP)]. Activation of the intrinsic pathway of coagulation was clearly
      demonstrated by elevated levels of factor XIa--C1-inhibitor complexes, without
      evidence of contact activation, reflected by undetectable kallikrein--C1
      inhibitor complexes. Both TAFI antigen and activity levels were decreased in all
      patients, which may contribute to the severity of bleeding complications in DHF
      because of the impaired capacity of the coagulation system to protect the fibrin
      clot from fibrinolysis. These findings in a human viral infection model are in
      accordance with earlier findings in bacterial sepsis.

PMID- 11328288
TI  - Microangiopathic haemolytic anaemia in metastasizing malignant tumours is not
      associated with a severe deficiency of the von Willebrand factor-cleaving
      protease.
AB  - Complete deficiency of von Willebrand factor-cleaving protease (VWF-cp) has
      recently been identified as a pathogenetically important factor for thrombotic
      thrombocytopenic purpura (TTP). Microangiopathic haemolytic anaemia (MAHA) with
      thrombocytopenia in patients with metastasizing neoplasms is clinically similar
      to TTP, however, the pathogenesis of the condition is unclear. Partial deficiency
      of VWF-cp in metastasizing malignancy has recently been reported in patients
      without MAHA. Our study shows normal or subnormal VWF-cp activity in four
      patients with metastasizing neoplasia-associated MAHA but, in contrast to
      classical TTP, no complete deficiency of VWF-cp despite the full clinical picture
      of MAHA.

PMID- 11328289
TI  - Determinants of outcome after intensified therapy of childhood lymphoblastic
      leukaemia: results from Medical Research Council United Kingdom acute
      lymphoblastic leukaemia XI protocol.
AB  - The single most important prognostic determinant in childhood acute lymphoblastic
      leukaemia (ALL) is effective therapy and changes in therapy may influence the
      significance of other risk factors. The effect of intensified therapy on the
      importance of currently recognized phenotypic and genotypic determinants of
      outcome was assessed in 2090 children enrolled on the Medical Research Council
      United Kingdom acute lymphoblastic leukaemia XI (MRC UKALL XI) protocol.
      Treatment allocation was not determined by risk factors. Multivariate analysis
      confirmed the dominant influence on prognosis of age, sex and presenting white
      cell count (WCC). After allowing for these features, blast karyotype, d 8 marrow
      blast percentage and remission status at the end of induction therapy were the
      only remaining significant predictors of outcome. Organomegaly, haemoglobin
      concentration, French--American--British type, body mass index, presence of
      central nervous system disease at diagnosis, immunophenotype and presence of
      TEL/AML1 fusion gene (examined in a subset of 659 patients) either had no
      significant effect on outcome or were significant only in univariate analysis.
      Among karyotype abnormalities with an independent influence on prognosis, high
      hyperdiploidy (> 50 chromosomes) was shown to be favourable, whereas near
      haploidy (23--29 chromosomes), presence of the Philadelphia chromosome, t(4;11)
      and abnormalities affecting the short arm of chromosome 9 [abn (9p)] were adverse
      risk factors. Early responders to therapy, determined by residual marrow
      infiltration after 8 d of induction therapy, had a good outcome, while the small
      proportion of patients who did not achieve a complete remission by the end of
      induction therapy had a poor outcome. A third block of late intensification was
      shown to improve event-free survival by 8% at 5 years. The effect of these risk
      factors was not significantly different between those randomized to the third
      intensification block and those not randomized to a third block.

PMID- 11328291
TI  - Cytogenetic risk groups in acute myeloblastic leukaemia differ greatly in their
      semi-solid colony growth.
AB  - We have analysed the results of semi-solid bone marrow cultures in 296 patients
      with de novo acute myeloblastic leukaemia (AML) and correlated them with the
      leukaemic karyotype. A favourable prognostic karyotype was found in 52 patients
      (group A, 18.3%), an intermediate karyotype in 163 patients (group B, 57.4%), and
      unfavourable cytogenetics were observed in 69 patients (group C, 24.3%). Median
      colony growth according to the three risk groups was 2 (range 0--344) in group A,
      14.5 (range 0--5000) in group B and 50.0 (0--3000) in group C (A vs. B, P <
      0.001; A vs. C, P < 0.001; B vs. C, P < 0.01). Among the patients treated with
      chemotherapy (n = 257), median colony growth was 10 (range 0-5000) in those who
      achieved complete remission (CR) compared with 56.5 (range 0-1000) in patients
      without remission (NR) (P = 0.002). The median colony growth of all patients
      [13/10(5) bone marrow mononuclear cells (BMMCs); range 0--5000] significantly
      discriminated between patients regarding survival (OS 11 vs. 7 months, P =
      0.044). However, multiple Cox regression analysis revealed cytogenetic risk
      groups as the most important predictor for achieving CR, disease-free and overall
      survival, with colony growth adding no additional prognostic information. In 64
      patients, colony growth was also investigated without the addition of exogenous
      cytokines. Interestingly, none of the patients with a favourable karyotype
      exhibited autonomous growth, whereas 50% with an intermediate and 73% of patients
      with an unfavourable karyotype displayed either partial or full autonomous growth
      in vitro (P = 0.0004). Our data suggest that the growth potential of the
      leukaemic clone seems to be critically influenced by the molecular changes
      emerging from chromosomal abnormalities.

PMID- 11328290
TI  - Drug monitoring of low-dose PEG-asparaginase (Oncaspar) in children with relapsed
      acute lymphoblastic leukaemia.
AB  - Use of asparaginase (ASNase) in the treatment of relapsed childhood acute
      lymphoblastic leukaemia (ALL) is associated with a high rate of hypersensitive
      reactions. 'Silent' inactivation may additionally reduce treatment intensity.
      Therefore, PEG-ASNase (Oncaspar), a polyethylene glycol conjugate of the native
      Escherichia coli-ASNase, was introduced into the Berlin-Frankfurt-Munster (BFM)
      96 treatment protocol for relapsed ALL under drug monitoring conditions. A single
      i.v. dose of 500 IU/m2 PEG-ASNase, substituted for the native ASNases, was
      administered to supply a plasma activity of 100 IU/l for 1 week. From November
      1997 to March 2000, 35 patients from 23 BFM-associated hospitals, with or without
      a previous allergic reaction to one or both native preparations, underwent
      monitoring. After 82 applications, a total of 270 samples were submitted to be
      tested for ASNase activity. The ASNase activity on the day of the administration
      and the following day ranged between < 20 and 693 IU/l, with a median of 413 IU/l
      (53 samples). The median on d 7 +/- 1 was 199 IU/l (range <20--421 IU/l; 41
      samples) and on d 14 +/- 1, 105 IU/l (range <20--188 IU/l; 19 samples). An ASNase
      activity of > 100 IU/l was seen on d 7 in 36 activity time courses of 52
      interpretable applications (69%). Intraindividual variability of activity time
      courses was low. However, a rapid decrease in ASNase activity after repeated
      applications was observed in 4 out of 20 children. Previously experienced
      allergic reactions to native ASNases did not influence PEG-ASNase
      pharmacokinetics. PEG-ASNase is a useful alternative to the native ASNases in
      children with relapsed ALL. Whenever possible, drug monitoring should be
      performed to identify patients with 'silent' inactivation.

PMID- 11328292
TI  - The apoptogenic response of human myeloid leukaemia cell lines and of normal and
      malignant haematopoietic progenitor cells to the proteasome inhibitor PSI.
AB  - Degradation of several intracellular proteins involved in cell cycle control and
      tumour growth is regulated by the ubiquitin-dependent multicatalytic protease
      complex (proteasome). We report that proteasome inhibitor Z-Ile-Glu(OtBu)-Ala
      Leucinal (PSI) was cytotoxic on most human myeloid leukaemia cell lines at IC50
      doses ranging from 5 to 25 nmol/l. Additionally, PSI pre-treatment enhanced
      cytotoxicity by taxol and cisplatinum. PSI was more active on leukaemic than on
      normal CD34(+) bone marrow progenitors because the 50% growth inhibition of
      colony-forming unit granulocyte macrophage (CFU-GM) from cases of chronic
      myelogenous leukaemia (CML) and normal subjects was achieved by 15 nmol/l and 50
      nmol/l PSI respectively. PSI killed cells by apoptosis as revealed by
      ultrastructural changes, nuclear DNA fragmentation, cleavage of poly (ADP-ribose)
      polymerase (PARP) and of beta-catenin, and was antagonized by ectopic expression
      of Bcl-2 but not by inactivating mutations of p53. This event was associated with
      a slight accumulation of Bcl-2, a decrease of Bax but no changes in Bcl-X(L)
      protein expression at any time point. In Ph(+) cell lines BCR-ABL protein was
      only down-regulated after 48 h of treatment with 10 nmol/l PSI. Altogether, these
      results indicate that PSI, alone or in association with other cytotoxic agents,
      has anti-tumour activity against myeloid malignancies and is more effective on
      leukaemic than on normal haematopoietic progenitor cells.

PMID- 11328293
TI  - Phenotypic and functional characterization of the host immune compartment of
      chronic myeloid leukaemia patients in complete haematological remission.
AB  - The role of the host immune compartment in the control of chronic myeloid
      leukaemia (CML) has been suggested by numerous biological and clinical evidence.
      In the present study, the phenotypic and functional machinery of both T and
      cytotoxic lymphocytes was evaluated in a series of CML patients in complete
      haematological, and frequently also in cytogenetic, remission after treatment
      with interferon (IFN) alpha or hydroxyurea, and compared with the profile
      observed in patients at diagnosis and in normal controls. In particular, the
      lymphocyte subset distribution, the cytotoxic activity and the intracellular
      production of tumour necrosis factor (TNF)alpha and IFN gamma by CD4(+), CD8(+)
      and CD56(+) cells were investigated. CML patients in complete haematological
      remission showed a normalized CD4/CD8 T-cell subset distribution, as well as a
      restored spontaneous and interleukin 2 (IL-2) induced cytotoxic function compared
      with the pattern observed at diagnosis. This was associated with a significantly
      increased proportion of activated CD4(+) lymphocytes (CD25(+)). TNF alpha and IFN
      gamma production by CD4(+), CD8(+) and CD56(+) lymphocytes was significantly
      enhanced compared with that of patients at diagnosis. However, the values were
      lower than those of normal controls. These results indicate that, in contrast to
      the observations at presentation, CML patients, at the time of the best possible
      response to treatment, show a normalized T-cell subset distribution associated
      with an activated CD4 T-cell compartment and a restored cytotoxic activity. In
      addition, they also show a markedly increased intracellular cytokine production
      by the lymphoid populations that play an important role in the process of
      specific tumour recognition. The design of therapeutic strategies aimed at
      stimulating the host immune compartment finds a further rationale for CML
      patients responsive to treatment with both IFN alpha and hydroxyurea.

PMID- 11328294
TI  - Molecular characterization of a myelodysplasia-associated chromosome 7 inversion.
AB  - Chromosome 7 abnormalities are observed in a wide range of myeloid disorders,
      particularly myelodysplasia (MDS) and acute myeloid leukaemia (AML). Monosomy 7
      and 7q deletions are the most frequent abnormalities, although translocations and
      inversions involving 7q also occur. The region 7q22--q34 may contain as many as
      four distinct minimal regions of deletion (MDRs), which are thought to contain
      one or more myeloid tumour-suppressor genes. We have defined previously the
      proximal breakpoint of a constitutional 7q22--q34 inversion, carried in a cell
      line derived from a member of a family with a history of MDS. A YAC clone
      spanning this breakpoint was identified. Both inversion breakpoints have now been
      cloned and sequenced, placing the proximal breakpoint 40 kb centromeric to the
      TAC2 (tachykinin 2) gene and the distal breakpoint 42 kb telomeric to the SSBP
      (mitochondrial single-stranded DNA-binding protein) gene. Sequence alignments
      revealed small (3--4 bp) duplications at the inversion breakpoints, suggesting
      that the mechanism of inversion involved the creation of staggered breaks and
      filling in of the overhanging ends. A 190-bp Alu--Alu deletion close to the
      distal breakpoint was also detected and may have contributed to the inversion.

PMID- 11328295
TI  - Killer T-cell induction in patients with blastic natural killer cell
      lymphoma/leukaemia: implications for successful treatment and possible
      therapeutic strategies.
AB  - A rare form of putative natural killer (NK) cell lymphoma called blastic NK cell
      lymphoma appears to be clinicopathologically distinctive in showing a homogenous
      lymphoblast, variable expression of CD2, CD4, CD56 and TdT, negative for surface
      CD3, T-cell receptor antigen, CD16, CD34 and lack of association with Epstein
      Barr virus (EBV). We report two patients with blastic NK cell lymphoma and
      describe the interesting clinical studies. The patients presented with cutaneous
      plaques. Both patients had adenopathy, and one had marrow involvement at
      presentation. Unlike in many NK and NK-like T-cell disorders, azurophilic
      cytoplasmic granules were absent. They expressed intermediate density CD45. In
      addition, the cells were positive for HLA-DR, CD2, CD4, CD56 and TdT, and
      negative for EBV transcripts. In spite of the advanced clinical stage, complete
      remission was achieved by conventional chemotherapy. After interleukin 2
      expansion of tumour-infiltrating bone marrow and lymph node cells from the
      patients, cytotoxic T-cell lines with rearranged T-cell receptor genes were
      established. They showed specific killing activity against autologous tumour
      cells in an MHC-restricted fashion, with possible implications for treatment. In
      addition, upon cessation of maintenance chemotherapy, one patient developed overt
      leukaemia with blasts expressing CD33 antigens, suggesting a continuous spectrum
      of blastic NK cell lymphoma to myeloid/NK cell precursor acute leukaemia.

PMID- 11328296
TI  - Long-term follow-up in patients treated with Mini-BEAM as salvage therapy for
      relapsed or refractory Hodgkin's disease.
AB  - Several studies have focused on investigation of the optimal salvage regimen to
      induce maximum response before autologous stem cell transplantation (ASCT) in
      patients with relapsed or refractory Hodgkin's disease (HD). However, in most of
      these studies, the follow-up is relatively short. In the present study, we report
      on long-term results of 55 consecutive patients with HD who received Mini-BEAM
      [BCNU (carmustine), etoposide, cytarabine, melphalan] as salvage therapy before
      ASCT. Eleven patients were refractory to front-line therapy, 17 were partial
      responders, and 27 patients had relapsed from HD. Twenty-eight patients achieved
      complete response, and 18 achieved partial response with a median of two cycles
      of Mini-BEAM, giving a total response rate of 84%. Significant factors predicting
      poor response (P < 0.05) were: initial treatment with MOPP (mechloroethamine,
      oncovin, procarbazine, prednisolone), > or = two previous chemotherapy regimens
      and three disease characteristics at Mini-BEAM treatment: presence of B symptoms,
      extranodal involvement or low serum albumin. However, only the last two factors
      retained independent influence on multivariate analysis. In total, 45/55 patients
      have been transplanted. Median follow-up after Mini-BEAM administration for
      living patients is 68 months. At the time of reporting, 31 out of 55 patients
      (56.4%) are still alive, 21 patients (38%) have relapsed, three (5.4%) have
      developed secondary neoplasias, and five have died of other complications not
      related to disease progression. The actuarial 7-year overall survival (OS) was
      52%, the progression-free survival (PFS) 54% and the event-free survival (EFS)
      36%. The response to Mini-BEAM was the most important prognostic factor for
      predicting the long-term probability of surviving the disease: none of the eight
      patients who did not respond to Mini-BEAM were alive at 3 years. On multivariate
      analysis, response to Mini-BEAM and extranodal involvement before Mini-BEAM had a
      significant influence on OS. Our results show the safety and efficacy of Mini
      BEAM before ASCT for refractory or relapsed HD patients.

PMID- 11328298
TI  - Screening for Aspergillus spp. using polymerase chain reaction of whole blood
      samples from patients with haematological malignancies.
AB  - Sensitive screening for Aspergillus spp. using polymerase chain reaction (PCR) of
      whole blood samples in patients with haematological disorders has not been
      performed to date. In a 2-year study, 121 patients admitted to the University
      Hospital of Innsbruck for cancer chemotherapy without clinical signs of fungal
      infection were prospectively screened for Aspergillus spp. In 28 out of 121 (23%)
      patients, Aspergillus DNAaemia was detected. Of these patients, 16 (57%) were
      positive only once for Aspergillus DNA, but positivity was never associated with
      invasive aspergillosis. PCR positive episodes were short and resolved without
      antifungal treatment. Five patients (18%) had intermittent PCR positive results.
      Seven (25%) patients presented at least two consecutive positive PCR results; one
      of these patients developed invasive aspergillosis and another two were strongly
      suspected as having aspergillosis. Based on the criteria of the European
      Organization for Research and Treatment of Cancer case definitions, sensitivity
      and specificity of serial PCR monitoring were 75% and 96%. Positive PCR results
      became negative shortly after commencement of antifungal treatment, but the
      changes did not correlate with clinical responsiveness to treatment in three
      patients. Our results indicate the potential usefulness of PCR for screening for
      Aspergillus spp. in patients at risk, but without antifungal treatment.

PMID- 11328297
TI  - Efficacy of epoetin alfa in the treatment of anaemia of multiple myeloma.
AB  - Effects of epoetin alfa on transfusions, haemoglobin (Hb) and quality of life
      (QOL) were evaluated in a placebo-controlled study of 145 patients with multiple
      myeloma and anaemia (Hb < 11 g/dl). During the 12-week, double-blind phase,
      patients received 150 IU/kg epoetin alfa or a matching volume of placebo
      subcutaneously three times weekly; the dose (or volume) was doubled at week 4 if
      Hb response was inadequate. Patients completing this phase could enter the
      subsequent optional 12-week phase of open-label epoetin alfa treatment. During
      double-blind treatment, epoetin alfa significantly decreased the incidence of
      transfusion compared with placebo (28% vs. 47%, P = 0.017), regardless of
      patients' transfusion history, and increased mean Hb (1.8 g/dl vs. 0.0 g/dl, P <
      0.001). Univariate analysis showed significant (P </= 0.05) improvement in more
      QOL measures with epoetin alfa than with placebo; multivariate analysis discerned
      no between-treatment differences. Significantly (P = 0.038) more epoetin alfa vs.
      placebo patients had improved performance scores. At the end of the open-label
      treatment phase, patients who had continued epoetin alfa maintained Hb status,
      and placebo patients who were switched to epoetin alfa had mean Hb increases of
      2.4 g/dl. Adverse events were similar between treatment groups. Epoetin alfa
      proved effective and well tolerated for treating anaemia in patients with
      multiple myeloma.

PMID- 11328299
TI  - Treatment of refractory T-cell malignancies using gemcitabine.
AB  - We have treated 10 patients with relapsed or refractory T-cell malignancies using
      gemcitabine. The drug was administered intravenously over 30 min at a dose of
      1200 mg/m2 on d 1, 8 and 15 of each 28-d cycle. The mean age of the patients was
      62 years and the mean number of administered cycles was three. Of the 10
      patients, two achieved a complete response and four a partial response, for an
      overall response rate of 60% (95% confidence interval 20--35%). The toxicity of
      chemotherapy was mild and manageable in all patients. These encouraging results
      warrant further investigation of gemcitabine either as a single agent or in
      combination regimens as early salvage treatment for patients with refractory T
      cell haematological neoplasms.

PMID- 11328300
TI  - Human herpesvirus 8 DNA sequences are present in bone marrow from HIV-negative
      patients with lymphoproliferative disorders and from healthy donors.
AB  - Bone marrow (BM) from patients affected by multiple myeloma (MM), exhibiting
      monoclonal gammopathy of undetermined significance (MGUS) or with non-Hodgkin
      lymphoma (NHL) as well as from healthy donors were investigated for the presence
      of human herpesvirus-8 (HHV-8) DNA sequences. ORF 26 sequences were detected in
      36--56% of the patients and in 29% of the controls. In a few cases, two other HHV
      8 DNA sequences were also detected. These observations indicate that the presence
      of the HHV-8 genome in BM is relatively common in different groups of patients as
      well as in healthy individuals and do not support an alleged role for HHV-8 in
      MM.

PMID- 11328301
TI  - High-grade lymphoma mimicking bone crisis in Gaucher's disease.
AB  - A 33-year-old woman with type 1 Gaucher's disease developed painful swelling of
      her right tibia. Initial diagnostics suggested a typical bone crisis. However,
      clinical course and subsequent imaging pointed to malignant disease, which was
      specified as high-grade lymphoma. Chemotherapy was applied together with enzyme
      replacement and resulted in complete remission of the lymphoma. We conclude that
      osseous lesions, although suggestive of common manifestations of Gaucher's
      disease, should be discriminated very carefully from neoplastic infiltration to
      maintain curative treatment options.

PMID- 11328302
TI  - Health and functional status of adult recipients 1 year after allogeneic
      haematopoietic stem cell transplantation.
AB  - Increasing numbers of patients are surviving after allogeneic haematopoietic stem
      cell transplantation (SCT). Among these patients, a number of late complications
      have been described but few data on the risk factors of these long-term effects
      of SCT are available. We report the analysis on 105 adult patients, surviving
      free of haematological disease at a median time of 15 months after SCT. At the
      time of screening, 52% had returned to work, general health status was normal in
      67% and 47% were sexually active. Female patient gender odds ratio (OR) 2.9 (P =
      0.01) and age > 25 years (OR = 3.2, P = 0.02) were associated with non-return to
      work. Decreased general status was associated with chronic graft-versus-host
      disease (GvHD) (OR = 3.2, P = 0.009) and irradiation (OR = 3.6, P = 0.004).
      Sexual inactivity was associated with younger age (OR = 7.0, P = 0.0002) and
      chronic GvHD (OR = 3.3, P = 0.006). Risk factors for altered pulmonary function
      tests included previous smoking habits, irradiation and chronic GvHD. Obstructive
      lung disease was associated with a previous history of asthma. Sicca syndrome and
      conjunctivitis were increased in patients with previous acute GvHD and cataracts
      were less frequent in patients with aplastic anaemia. Persistent impaired hair re
      growth was less frequent in patients who received irradiation (OR = 0.18, P =
      0.002) but increased in patients with previous acute GvHD (OR = 5.3, P = 0.007).
      Microalbuminuria was more frequent in irradiated patients (OR = 9.4, P = 0.05).
      Raised cholesterol was associated with age (OR = 20.8, P < 0.001), previous acute
      GvHD (OR = 4.7, P = 0.03), steroid use (OR = 6.3, P = 0.001) and familial
      hypercholesterolaemia (OR = 4.4, P = 0.04). Decreased bone density was associated
      with chronic GvHD (OR = 3.9, P = 0.001). Thus, using routine tests in adult
      patients we were able to detect significant numbers of-non-symptomatic
      complications enabling early treatment.

PMID- 11328303
TI  - Autotransplants for histologically transformed follicular non-Hodgkin's lymphoma.
AB  - Histological transformation from a follicular non-Hodgkin's lymphoma (NHL) to a
      higher grade lymphoma carries a poor prognosis despite treatment with aggressive
      anthracycline-based chemotherapy. We retrospectively analysed 35 patients with
      histologically transformed NHL who underwent high-dose therapy and
      autotransplantation at our centre. Patients up to 65 years old were eligible for
      autotransplant at the time of transformation or with subsequent relapses,
      provided that chemosensitivity to a salvage regimen could be demonstrated. All
      patients received high-dose therapy [etoposide 60 mg/kg, melphalan 160 mg/m2 and
      fractionated total body irradiation (TBI) 12 Gy] followed by unpurged autologous
      bone marrow or blood stem cell rescue. Most patients (69%) had advanced stage
      disease (stages 3--4) at transformation and bone marrow involvement was common
      (49%). Twenty-six (74%) patients were in partial remission (PR) and nine (26%) in
      complete remission (CR) at the time of transplant. Median duration from
      transformation to transplant was 10.9 months (range, 5.2 months--4.6 years). At a
      median follow up of 52 months after autotransplant, 19 (54%) patients had died.
      Causes of death were progressive lymphoma in nine patients (26%), treatment
      related mortality (TRM) in seven (20%) and myelodysplasia in three (8%). Only
      five patients in our cohort were > 60 years old, but all died as a result of
      treatment-related causes (mostly pulmonary infections). Five-year overall
      survival and progression-free survival from time of transplant were 37% and 36%
      respectively. Using multivariate analysis of factors including gender, age,
      stage, extranodal disease, disease bulk, B symptoms, number of prior therapies,
      relapse status and CR/PR status at transplant, only advanced age significantly
      predicted for survival from autotransplant (P = 0.002). Our survival data are
      comparable to previous reports of autotransplantation for transformed NHL and
      suggest a benefit over standard chemotherapy alone in selected patients. However,
      our high TRM cautions the use of aggressive therapy, including TBI, in patients
      over 60 years old.

PMID- 11328304
TI  - Combination therapy with tacrolimus and anti-thymocyte globulin for the treatment
      of steroid-resistant acute graft-versus-host disease developing during
      cyclosporine prophylaxis.
AB  - We report our experience with the combination of anti-thymocyte globulin (ATGAM)
      and tacrolimus in the treatment of 20 patients with steroid refractory and
      dependent acute graft-versus-host disease (GVHD) transplanted between August 1996
      and February 2000. All patients received cyclosporine-based GVHD prophylaxis.
      Thirteen patients developed a maximum of grade IV, five grade III and two grade
      II acute GVHD, with 15 patients being refractory to steroids and five dependent
      on steroids. Patients were treated with ATGAM (15 mg/kg for 5 d) and tacrolimus
      (0.025--0.1 mg/kg/d) in addition to continuation of their high-dose steroids and
      cessation of their cyclosporine. Within 28 d of treatment, we observed eight
      complete responses (CR), six partial responses (PR) and six with no response.
      Overall response (CR + PR) was predicted by GVHD severity. Infectious
      complications occurred in 80% of patients. The median survival was 86.5 d (range,
      21--1081 d) with 35% of patients remaining alive. Survival following combination
      therapy was significantly more likely in men (P < 0.001), skin-only GVHD (P =
      0.027), less severe GVHD (P = 0.048), and in responders to tacrolimus and ATGAM
      (P < 0.001). In conclusion, concurrent introduction of ATGAM and tacrolimus is a
      promising therapeutic combination for GVHD refractory to steroids and
      cyclosporine.

PMID- 11328305
TI  - Changes in the pattern of TCR V beta repertoire expression after bone marrow
      transplant is linked to the HLA haplotype in humans.
AB  - Neutrophil, monocyte, natural killer- and B-cell number and function are rapidly
      restored after bone marrow transplant (BMT), whereas T-cell reconstitution is
      often quite delayed. Our hypothesis was that V beta T-cell receptor (TCR)
      repertoire diversity among recipients of allogeneic BMT is influenced by the
      expression of major and minor HLA antigens in the host. The study population
      comprised unmanipulated and CD34(+)-selected allogeneic bone marrow grafts,
      autologous peripheral blood stem cell transplants and recipients of volunteer
      unrelated donor (VUD) bone marrow transplants. Using flow cytometry, the relative
      frequencies of 18 V beta TCR families were determined and ranked for each time
      point studied. Comparisons and correlations were made between paired blood
      samples obtained within a single patient over time, and between donors and their
      recipients. The pattern of the V beta TCR repertoire from allogeneic recipients
      and their HLA-matched donors was very similar, with a correlation coefficient
      (CC) of 0.59. This similarity was not as marked in VUD pairs (CC = 0.32). By 3
      months after transplant, the pattern of the V beta TCR repertoire in recipients
      of HLA-matched sibling transplants was more similar to the pattern seen in
      pretransplant recipients than to the donor pattern (CC = 0.40 vs. 0.31). Our data
      suggest that both major and minor HLA antigens influence V beta TCR repertoire
      diversity and reconstitution after BMT.

PMID- 11328306
TI  - Ex vivo generation of human cytomegalovirus-specific cytotoxic T cells by peptide
      pulsed dendritic cells.
AB  - Adoptive transfer of donor-derived human cytomegalovirus (HCMV)-specific T-cell
      clones can restore protective immunity after stem cell transplantation. Ex vivo
      induction of HCMV-specific T cells using HCMV-infected fibroblasts as stimulator
      cells confines this approach to HCMV-seropositive donors and requires the
      presence of infectious virus during the stimulation procedure. In this study, we
      describe a potential alternative strategy to generate HCMV-specific T cells ex
      vivo for adoptive immunotherapy. Generation of HCMV-specific cytotoxic T
      lymphocytes (CTLs) ex vivo was investigated using peptide-pulsed dendritic cells
      as antigen-presenting cells. HCMV-specific T cells were generated and
      sufficiently expanded for adoptive immunotherapy in 6 out of 14 HCMV-seropositive
      and 2 out of 11 HCMV-seronegative donors. The CTLs recognized HCMV-infected
      autologous fibroblasts. No lysis was observed with either non-infected autologous
      or HLA-mismatched infected fibroblasts. Staining with tetrameric HLA/peptide
      complexes revealed significant enrichment for peptide-specific T cells of up to
      28% and > 90% of CD8(+) T cells after three and five specific stimulations
      respectively. In addition, the expansion rates indicated that ex vivo generation
      of > 1 x 10(9) HCMV-specific T cells was possible after 6--7 weeks when cultures
      were initiated with 1--5 x 10(6) responder cells. Thus, the approach with peptide
      pulsed DCs to generate HCMV-specific CTLs is feasible for clinical application
      after allogeneic stem cell transplantation.

PMID- 11328307
TI  - Decreased yield, phenotypic expression and function of immature monocyte-derived
      dendritic cells in cord blood.
AB  - Dendritic cells are critical for the induction of both primary immune responses
      and immunological tolerance, as well as for the regulation of T-helper 1 (Th1)
      and 2 (Th2) immune responses. As neonates are notably deficient in Th1 response
      and cord blood transplantation is noted to result in less graft-versus-host
      disease (GvHD), we compared the phenotypic and functional characteristics of
      monocyte-derived dendritic cells (DCs) that favour Th1 development from cord
      blood and adult peripheral blood to understand the underlying mechanisms of these
      observations. Our results showed that: (1) after culture for 7 d with interleukin
      (IL)-4 and granulocyte--macrophage colony-stimulating factor (GM-CSF), cord blood
      monocytes generated less CD1a(+) cells than adult peripheral blood monocytes, and
      the CD1a+ cell percentage decreased thereafter; (2) compared with adult blood
      DCs, cord blood DCs had reduced intensity of expression of CD1a and MHC class II
      molecules, but the expression levels of CD11c and CD86 were similar; (3) the
      endocytotic ability of cord blood DCs was reduced compared with adult blood DCs,
      and this function was related to reduced mannose receptor (MR)-positive cells;
      (4) furthermore, the ability of cord blood DCs to stimulate CD3(+) T cells in an
      allogeneic mixed lymphocyte reaction was significantly lower than that of adult
      blood DCs. These results suggested that the dysfunction of cord blood monocytes
      in differentiating into professional DCs will affect the activation of naive T
      cells, especially Th1 development, and may be related to the susceptibility to
      different infections in the neonates, as well as the lower incidence of GvHD in
      cord blood transplantation.

PMID- 11328308
TI  - Association between the SDF1-3'A allele and high levels of CD34(+) progenitor
      cells mobilized into peripheral blood in humans.
AB  - Some patients unexpectedly fail to mobilize sufficient numbers of haematopoietic
      progenitor cells (HPCs) into the peripheral blood for autologous transplantation.
      Considering the important role of the chemokine stromal cell-derived factor 1
      (SDF-1) in HPC homing, we investigated a possible relationship between SDF1 gene
      polymorphism and HPC mobilization capacity in 63 patients with malignancy. Some
      67% of the good mobilizers (> or = 50 CD34(+) cells/microl) and only 36% of the
      intermediate/poor mobilizers were SDF1-3'A allele carriers (P = 0.032). In
      multivariate analysis, the presence of the SDF1-3'A allele was the only factor
      predictive of good CD34(+) cell mobilization (P = 0.025). This is the first
      report showing the involvement of genetic factors for HPC mobilization in humans
      and suggests a significant role for SDF-1 in this process.

PMID- 11328309
TI  - Graft-versus-host disease and survival after ABO-incompatible allogeneic bone
      marrow transplantation: a single-centre experience.
AB  - The effect of ABO-incompatibility on graft versus host disease (GVHD) and
      survival was evaluated in 173 consecutive patients receiving allogeneic bone
      marrow transplantation (BMT). Thirty-four percent of the patients developed GVHD
      and univariate analysis suggested a higher incidence of GVHD in minor ABO
      incompatibility than in ABO-identity (14/30, 47% versus 37/112, 33%; P = 0.02).
      However, using logistic regression adjusted for potential confounders, the GVHD
      risk did not differ significantly. During a mean follow-up time of 59 months, the
      mortality was 37% and survival was significantly dependent on ABO-compatibility
      (P = 0.004). In particular, patients with bidirectional ABO-incompatibility had
      an excess mortality rate (RR, 7.6; 95% CI, 2.5-23.2; P = 0.0004). Taken together,
      these results suggest that ABO-incompatibility may represent a risk factor in
      allogeneic BMT.

PMID- 11328310
TI  - TEL/AML1 fusion is not a prognostic factor in Dutch childhood acute lymphoblastic
      leukaemia.

PMID- 11328311
TI  - Will the high rates of post-treatment sexual stage parasitaemia seen in malaria
      endemic areas make the optiMAL antigen test unreliable in predicting malaria
      treatment outcome?

PMID- 11328313
TI  - Defense of breast cancer malpractice claims.
AB  - The goal of this study was to determine whether factors associated with the
      successful defense and cost of malpractice cases involving the failure to
      diagnose breast cancer could be identified in medical and legal records.
      Secondary goals were to develop a multidisciplinary clinical algorithm utilizing
      National Comprehensive Cancer Network (NCCN) practice guidelines with
      practitioner risk management strategies. Physician deviations from these
      guidelines were tracked to identify high-risk areas in the diagnosis of breast
      cancer. A multidisciplinary clinical algorithm was introduced and practitioner
      risk management issues were addressed. In this study specific medical, legal, and
      cost factors were retrospectively abstracted and analyzed to identify
      associations between medical and legal factors and medicolegal outcome. ProMutual
      handled 156 malpractice cases involving breast cancer between January 22, 1986,
      and November 20, 1997. Of the total, 124 cases involving 212 defendants were
      closed. The closed cases were analyzed, using multivariable stepwise logistic and
      linear regression, to identify associations between clinical factors and case
      outcome. Women's health practitioners (WHPs), including obstetrician
      gynecologists (OB-GYNs), family medicine, and internal medicine clinicians, were
      the largest group of defendants (97). Others included radiologists (43), surgeons
      (33), and pathologists (3). OB-GYNs accounted for 31% of these defendants, with a
      cost of more than $16 million. The greatest number of specialists represented in
      the open cases were radiologists, with 38% of the total. The defense model
      predicts that the probability of successful defense is lessened with inadequate
      record keeping, a patient that has metastasis and is alive, and a delay in
      diagnosis of 12 months or more. The overall indemnity model predicts a higher
      indemnity with the spread of disease at the time of evaluation, a patient who has
      metastasis and is alive, and a date of occurrence closer to the present.
      Indemnity is less in patients who have had a lymph node dissection, who have
      died, or who are alive without metastasis. The WHP model predicts an increased
      overall indemnity with the spread of disease at the time of evaluation and the
      presence of a mass without pain. Indemnity decreases with a history of pregnancy,
      absence of presenting symptoms, or presentation with pain with or without a mass,
      and the performance of a lymph node dissection.

PMID- 11328314
TI  - Breast conservation therapy with tumor bed irradiation alone in a selected group
      of patients with stage I breast cancer.
AB  - Radiotherapy after breast-conserving surgery increases local control. We tested
      the feasibility of limited surgery with tumor bed irradiation only with 192Ir in
      a selected group of patients with stage I breast cancer. Twenty-five breasts in
      24 women more than 60 years old with low- or intermediate-grade stage I tumors
      were treated with placement of interstitial catheters at the time of lumpectomy
      and axillary node dissection. This procedure was followed by after-loading with
      low-dose 192Ir to deliver 20-25 Gy to the tumor bed over 24-48 hours. There were
      neither local recurrences in the breast nor distant recurrences at a median
      follow-up of 47 months (range 25-90 months). Cosmetic appearance ranged from very
      good to excellent. There were no long-term complications. It is feasible to treat
      a select group of patients with tumor bed irradiation, using relatively low doses
      of interstitial irradiation, with excellent local control and no significant
      morbidity.

PMID- 11328315
TI  - Tamoxifen in breast cancer: symptom reporting.
AB  - Clinical studies have traditionally identified treatment-specific side effects by
      comparison of voiced side effects in treatment and placebo arms of a study.
      Highly motivated women in a clinical trial may underreport drug-induced symptoms
      for medications which may be considered lifesaving. Affective symptoms during
      treatment of early breast cancer with tamoxifen (an estradiol receptor
      antagonist) were reported as infrequent by the manufacturer. However, reports
      suggest a higher rate of depression during general use. The objective of the
      present study was to examine the frequency of symptoms that might be side effects
      of tamoxifen and to relate them to the way the women attributed such symptoms.
      The exploratory study involved semistructured telephone interviews of 25 women
      who were taking tamoxifen. Textual analysis of the information was used to
      examine the symptoms described by the women. They were also asked whether any
      symptoms were related to the medication. The symptoms and their attribution were
      evaluated against a background of self-perceived stress. The principal finding
      was a pattern of ambivalence in attributing symptoms to the drug. Of all the
      symptomatic changes noted, the women only attributed 51% to tamoxifen. Flushes,
      fatigue, and depression were reported most frequently during treatment; flushes
      were readily attributed to tamoxifen but depression and fatigue were attributed
      to another factor by half of the symptomatic women. Women who reported moderate
      to high levels of life stress were less likely to attribute symptoms to drug
      therapy. The results suggest that women taking tamoxifen may not attribute known
      drug side effects to use of the medication.

PMID- 11328316
TI  - Hamartomas of the breast: clinical, radiologic, and pathologic manifestations.
AB  - Between 1986 and 1996, 35 patients with a diagnosis of hamartoma of the breast
      were seen at the Mayo Clinic. One patient had two lesions. The mean age was 50
      years (range 21-86 years). Hamartomas were clinically identified as a palpable
      lump in 18 cases (11 were detected by the patient and 7 by a physician). The
      other 18 were identified mammographically. Twenty-four lesions were in the left
      breast and 12 were in the right breast; 39% were located in the upper outer
      quadrant. Mammographically most hamartomas were ovoid, and the lesions were well
      circumscribed. Sonographically they were all solid, but 24% showed cystic areas.
      Pathologically the mean greatest diameter was 3.2 cm (range 1.0-7.5 cm). All but
      one lesion showed circumscription. The mean percentage of fibrous tissue was 78%
      (range 5-95%), fat 13% (range 0-95%), and epithelium 9% (range 1.0-60%).
      Calcifications were seen in four lesions. Ductal hyperplasia was present in 27%
      and adenosis in 70% of lesions. Twelve percent of patients had coexistent
      fibroadenomas.

PMID- 11328317
TI  - MIB-1 index, S-phase fraction, mitotic figure count, and SBR histologic grading
      in invasive breast carcinoma: a comparative study.
AB  - Proliferative activity has been proven to be of prognostic significance in breast
      carcinoma. This study was performed to compare the different proliferative
      fractions in the Egyptian population and to define the most suitable one for
      daily routine use in our surgical pathology laboratories. The proliferative
      activity of 63 invasive ductal carcinomas was evaluated by immunohistochemical
      staining of paraffin-embedded tissue sections with MIB-1 rabbit polyclonal
      antibody and the heat-induced epitope retrieval method, flow cytometric
      determination of the S-phase fraction (SPF) on frozen tissues, and estimation of
      the Scarff-Bloom-Richardson (SBR) grading and mitotic figure count (MFC) on
      hematoxylin and eosin-stained tissue sections. Fifty-two percent of invasive
      ductal carcinoma were aneuploid. The mean values of MIB-1 index, SPF, and MFC
      were 17.7 +/- 12.3, 4.9 +/- 3.8, and 5.2 +/- 4.5, respectively, for diploid
      tumors; while for aneuploid tumors, they were 58.6 +/- 31.9, 19.9 +/- 12.2, and
      23.1 +/- 16.9, respectively. These values were significantly higher in aneuploid
      versus diploid tumors (p < 0.0001). A close correlation was found between MIB-1
      index, SPF, MFC, and SBR grading (p < 0.0001). In conclusion, in surgical
      pathology laboratories that cannot afford the costs of flow cytometry and/or
      immunostaining, proper SBR grading and MFC can provide an estimation of the
      proliferation fraction similar to the flow cytometric SPF and MIB-1
      immunostaining.

PMID- 11328318
TI  - Internal mammary lymph node inclusion in standard tangent breast fields: effects
      of body habitus.
AB  - The purpose of this study was to determine the variability of internal mammary
      node (IMN) coverage with standard breast tangent fields using surface anatomy as
      determined by computed tomography (CT) planning for patients treated with either
      breast-conserving treatment or postmastectomy, and to evaluate the influence of
      body habitus and shape on IMN coverage with standard tangent fields. This
      prospective study included consecutive women with breast cancer who underwent
      either local excision or mastectomy and had standard tangent fields intended to
      cover the breast plus a margin simulated using surface anatomy. CT planning
      determined the location of the IMN with respect to the tangent fields designed
      from surface anatomy. The internal mammary vessels were used as surrogates for
      the IMNs. CT measurements of the presternal fat thickness and anteroposterior
      (AP) and transverse skeletal diameters were made to determine their relationship
      to the inclusion of IMNs within the tangent fields. Only seven patients (14%) had
      their IMNs completely within the tangent fields. Twenty patients (40%) had
      partial coverage of their IMNs, and 23 (46%) had their IMNs completely outside
      the fields. IMN inclusion was inversely correlated with presternal fat thickness.
      Thoracic skeletal shape was not associated with IMN inclusion. Standard tangent
      fields generally do not cover the IMNs completely but may cover them at least
      partially in a majority of patients. The presternal fat thickness is inversely
      correlated with IMN inclusion in the tangent fields.

PMID- 11328319
TI  - Congestive heart failure mimicking inflammatory breast carcinoma: a case report
      and review of the literature.
AB  - Inflammatory breast cancer is a rare but highly malignant form of breast cancer.
      Biopsy and histologic examination usually confirm the diagnosis. There are rare
      reports of difficulties in differentiating this particular type of breast
      malignancy from congestive heart failure (CHF). This difficulty arises when CHF
      is associated with unilateral breast edema and skin thickening. However,
      inflammatory breast carcinoma has distinctive histologic and microscopic
      characteristics allowing the establishment of a proper diagnosis. We report the
      case of a 65-year-old woman with CHF associated with unilateral breast edema and
      skin thickening simulating inflammatory breast carcinoma on mammography.

PMID- 11328320
TI  - Angiosarcoma of the breast following breast preservation therapy and local
      radiation therapy for breast cancer.
AB  - This is a case of angiosarcoma following breast preservation therapy and local
      radiation therapy over a 3-year period.

PMID- 11328322
TI  - Innominate vein stenosis mimicking locally advanced breast cancer in a dialysis
      patient.

PMID- 11328321
TI  - Local recurrence of breast cancer in the stereotactic core needle biopsy site:
      case reports and review of the literature.
AB  - Early mammographic detection of nonpalpable breast lesions has led to the
      increasing use of stereotactic core biopsies for tissue diagnosis. Tumor seeding
      the needle tract is a theorectical concern; the incidence and clinical
      significance of this potential complication are unknown. We report three cases of
      subcutaneous breast cancer recurrence at the stereotactic biopsy site after
      definitive treatment of the primary breast tumor. Two cases were clinically
      evident and relevant; the third was detected in the preclinical, microscopic
      state. All three patients underwent multiple passes during stereotactic large
      core biopsies (14 gauge needle) followed by modified radical mastectomy. Two
      patients developed a subcutaneous recurrence at the site of the previous biopsy
      12 and 17 months later; one had excision of the skin and dermis at the time of
      mastectomy revealing tumor cells locally. In summary, clinically relevant
      recurrence from tumor cells seeding the needle tract is reported in two patients
      after definitive surgical therapy (without adjuvant radiation therapy). Often,
      the biopsy site is outside the boundaries of surgical resection. Since the core
      needle biopsy exit site represents a potential area of malignant seeding and
      subsequent tumor recurrence, we recommend excising the stereotactic core biopsy
      tract at the time of definitive surgical resection of the primary tumor.

PMID- 11328323
TI  - Granulomatous mastitis: diagnosis by ultrasound-guided core biopsy.

PMID- 11328325
TI  - Breast cancer patients in the new millennium.

PMID- 11328326
TI  - Diagnosis of motor neuropathy.
AB  - Motor neuropathy is a clinical entity which leads to consideration of a wide
      spectrum of peripheral nerve disorders. Firstly, it may be distinguished from
      other causes of peripheral motor involvement such as muscle diseases and
      disorders of the neuromuscular junction. Secondly, it may be discussed in two
      different forms: acute and chronic. Acute chronic neuropathies are mainly
      observed in Guillain-Barre syndrome, in which electrophysiological studies allow
      us to recognize the classical demyelinating form and the axonal form. The other
      causes of acute motor neuropathy are mainly poliomyelitis and porphyrias. Chronic
      motor neuropathies are mainly observed in motor neuron diseases, mainly
      amyotrophic lateral sclerosis, but also Kennedy's disease and other lower motor
      neuron diseases which may be inherited or acquired. The other causes are
      multifocal motor neuropathy and the predominantly motor forms of chronic
      inflammatory demyelinating polyneuropathy. The characterization of these
      different types of chronic neuropathy is of major importance because of the
      therapeutic consequences which may lead to the proposal of specific treatments.

PMID- 11328324
TI  - Locally advanced breast cancer: is surgery necessary?
AB  - A retrospective analysis of the treatment of locally advanced breast cancer
      (LABC) was undertaken at Stanford Medical Center to assess the outcome of
      patients who did not undergo surgical removal of their tumors. Between 1981 and
      1998, 64 patients with locally advanced breast cancer were treated with induction
      chemotherapy, radiation with or without breast surgery, and additional
      chemotherapy. Sixty-two (97%) patients received cyclophosphamide, doxorubicin,
      and 5-fluorouracil (CAF) induction chemotherapy. Induction chemotherapy was
      followed by local radiotherapy in 59 (92%) patients. Based on the clinical
      response to chemotherapy and patient preference, 44 (69%) patients received no
      local breast surgery. Radiotherapy was followed by an additional, non-doxorubicin
      containing chemotherapy in all patients. The mean age of patients was 49 years.
      Of the 65 locally advanced breast cancers in 64 patients, 26 (41%) were stage
      IIIA, 35 (55%) were stage IIIB, and 4 (6%) were stage IV (supraclavicular lymph
      nodes only). Response to induction chemotherapy was seen in 59 patients (92%),
      with 29 (45%) achieving a complete clinical response and 30 (47%) a partial
      clinical response. With a mean follow-up of 51 months (range 7-187 months), 43
      patients (67.2%) have no evidence of recurrent disease. Eight (12.5%) have
      recurred locally, and 21 (32.8%) have recurred with distant metastasis. Actuarial
      5-year survival is 75%, disease-free survival is 58%, and local control rate is
      87.5%. These data indicate that the routine inclusion of breast surgery in a
      combined modality treatment program for LABC does not appear necessary for the
      majority of patients who experience a response to induction chemotherapy.

PMID- 11328327
TI  - Movements in brain death.

PMID- 11328328
TI  - Task force on minimum standards for health care of people with multiple
      sclerosis: June 1999.

PMID- 11328329
TI  - Neurorehabilitation: a bridge between basic science and clinical practice.
AB  - A true paradigm shift or revolution of thinking is taking place in the field of
      neurology. Earlier, it was regarded as the science of exact diagnosis of
      incurable illnesses, according to the resigned dogma that damage to the central
      nervous system could not be repaired: "Once development is complete, the sources
      of growth and regeneration of axons and dendrites are irretrievably lost. In the
      adult brain the nerve paths are fixed and immutable: everything can die, nothing
      can be regenerated" (Cajal, 1928). Even then one could have countered this with
      what holds today: "Rehabilitation does not take place in the test tube!", and one
      would have been supported only a short time later by a most authoritative source,
      if one had read and quoted what the professor of neurology and neurosurgery in
      Breslau, Otfried Foerster, wrote in a 100-page article about therapeutic
      exercises that appeared in the Handbuch der Neurologie. From his introduction,
      only three sentences are quoted, which illustrate his opinion of the importance
      of therapeutic exercises and are closer to our views of brain functions today
      (Foerster, 1936): There is no doubt that most motor disturbances caused by
      lesions of the nervous system are more or less completely compensated as a result
      of a tendency inherent to the organism to carry out as expediently as possible
      the tasks of which it is capable under normal circumstances, using all the forces
      still available to it with the remaining undamaged parts of the nervous system,
      even following injury to its substance. This happens spontaneously, when neither
      a reversal of the noxa nor a regeneration of the destroyed tissue is possible,
      simply by means of a reorganization of the remaining parts of the nervous system,
      which is not a machine composed of individual parts that stands still when one
      part fails; rather, it possesses an admirable plasticity and exhibits an
      astonishingly extensive adaptability, not only to changed external conditions but
      also to disruptions of its own substance. Therapeutic exercises influence the
      course of spontaneous restoration; they support it, strengthen it. Not
      infrequently, in fact, they actually set it in motion when the forces essential
      to restoration lie fallow and are not deployed by the organism.

PMID- 11328330
TI  - Facial myokymia in brain death.
AB  - BACKGROUND: Brain death (BD) is the irreversible loss of all functions of the
      brain and brainstem. Spontaneous and reflex movements of the limbs have been
      described in this condition. However, facial myokymia (FM) in BD has not been
      previously reported. The origin of that motor phenomenon in alive patients is
      still uncertain, since supranuclear, nuclear and peripheral mechanisms have been
      proposed. OBJECTIVE: We describe the presence of FM in a patient who fulfilled
      the criteria for BD. A 40-year-old-man had right-sided weakness and impaired
      consciousness. After 14 h admission, he fulfilled the criteria for BD. A CT scan
      of the head showed a large putaminal hemorrhage. The EEG was isoelectric. At that
      time, fine spontaneous twitches of the left cheek were noticed. They consisted of
      repetitive and rhythmic movements in groups of 3-5 lasting for < 5 s. These
      movements appeared every 2-10 min during 6 h. DISCUSSION: Spinal reflexes have
      been described in BD. The presence of any movements other than the recognized
      reflexes may question this diagnosis and limit organ procurement for
      transplantation. The recognition of FM as an accepted movement in BD patients has
      practical and legal implications.

PMID- 11328331
TI  - Is the genetic liability in multifactorial disorders higher in concordant than
      discordant monozygotic twin pairs? A population-based family twin study of
      migraine without aura.
AB  - Migraine without aura (MO) is a multifactorial disorder. Expression of a disorder
      with multifactorial inheritance depends on the genetic liability and on
      environmental factors. A high liability is reflected by a high frequency of
      affected relatives. We have previously shown that monozygotic (MZ) twin pairs
      have a significant higher concordance of MO than dizygotic twin pairs. The
      incomplete concordance among MZ twin pairs may be due to a lower genetic
      liability among discordant than concordant MZ twin pairs. The present study
      analysed the genetic liability in MZ twin pairs concordant and discordant for MO
      by the population-relative risk of MO among parents and siblings. The twin pairs
      were from the population-based Danish Twin Register. First-degree relatives of 29
      concordant and 34 discordant MZ twin pairs were blindly telephone interviewed by
      a physician. The participation rate of the eligible first-degree relatives was
      96%. The population-relative risk of MO among parents and siblings was 2.73 (2.39
      3.06) in concordant and 2.37 (2.03-2.71) in discordant MZ twin pairs. The
      relative risk of MO was significantly higher in female first-degree relatives of
      concordant than of discordant MZ male and female twin pairs. An opposite effect
      was observed in male first-degree relatives, although this was not significant
      for male first-degree relatives of female MZ twin pairs. The present study found
      no statistically significant difference in genetic liability to MO among
      concordant and discordant MZ twin pairs. However, a difference in genetic
      liability among MZ and DZ twin pairs is anticipated to be small. Thus, it may be
      possible to show the effect in a larger study population or by investigating a
      more frequent trait than MO.

PMID- 11328332
TI  - Zolmitriptan versus sumatriptan for the acute oral treatment of migraine: a
      randomized, double-blind, international study.
AB  - This randomized, double-blind, parallel-group study compared the efficacy and
      tolerability of zolmitriptan (2.5 or 5 mg) and sumatriptan (50 mg) in the acute
      oral treatment of up to six moderate-to-severe migraine attacks. The intention to
      treat (ITT) population comprised of 1522 patients: 500 treated with zolmitriptan
      2.5 mg (2671 attacks), 514 with zolmitriptan 5 mg (2744 attacks) and 508 with
      sumatriptan 50 mg (2693 attacks). Overall, the 2-h headache response rates in
      these groups were 62.9, 65.7 and 66.6%, respectively. There were no statistically
      significant differences between sumatriptan 50 mg and zolmitriptan 2.5 mg (P =
      0.12) or 5 mg (P = 0.80). Approximately 40% of patients in each group reported a
      2-h headache response in > or = 80% of attacks. There were no statistically
      significant differences between the groups in the rates of headache response at 1
      h (zolmitriptan 2.5 mg 36.9%, zolmitriptan 5 mg 39.5% and sumatriptan 50 mg
      38.0%) or 4 h (70.3, 72.9 and 72.2%, respectively) or in the rates of meaningful
      migraine relief at 1, 2 or 4 h or sustained (24-h) pain relief. All treatments
      were well tolerated. In conclusion, zolmitriptan (2.5 or 5 mg) proved similarly
      efficacious compared with sumatriptan (50 mg), both in terms of response rates
      and consistency across attacks.

PMID- 11328333
TI  - Botulinum A toxin improves life quality in severe primary focal hyperhidrosis.
AB  - Focal hyperhidrosis is a condition that may disturb emotional, social and
      professional life. Treatment options for severe cases are surgical sympathectomy
      and local chemical sweat gland denervation by intradermal injections of botulinum
      toxin A (Btx A). The Dermatology Life Quality Index (DLQI) is a simple validated
      questionnaire designed to measure and compare disability in different skin
      diseases. The aim of this study was to assess quality of life with the DLQI
      before and after treatment with botulinum toxin injections in a group of patients
      with severe hyperhidrosis. DLQI was administered to 58 randomly chosen patients
      before and after treatment. All patients answered the DLQI questionnaire prior to
      treatment and 53/58 at mean 5.2 months after treatment. The mean DLQI score in
      the 58 patients before treatment was 10.3 (2-23). In the group of 16/53 patients
      who had a relapse of sweating when answering the DLQI a second time, no
      significant improvement was seen [score 10.6 before and 8.8 after treatment (P =
      0.21)]. In patients without relapse, a 76% improvement was obtained (DLQI was
      reduced from 9.9 to 2.4; P < 0.0001). The study showed that focal hyperhidrosis
      may considerably reduce life quality and the disability experienced by the
      patients can be largely reversed by botulinum toxin injections.

PMID- 11328334
TI  - Electrophysiological measures and dual-task performance in Tourette syndrome
      indicate deficient divided attention mechanisms.
AB  - Tourette syndrome has been associated with impairments of attentional functions
      such as distractability, even in subjects without co-morbid attention deficit
      hyperactivity disorder. Based on the results of earlier research we hypothesized
      that Tourette syndrome patients might employ altered control mechanisms of
      attentional processes and have concurrent difficulties in allocating their
      attentional resources among competing tasks. Event-related brain potentials
      (ERPs) were recorded in a group of Tourette syndrome patients and in a matched
      control group during a dual task experiment. This experiment required the
      simultaneous detection of visual and auditory target stimuli which were
      manipulated to yield two different difficulty levels each of which were varied
      orthogonally. The behavioural parameters confirmed the intended performance
      differences between difficult-to-detect targets and easy-to-detect targets. This
      was paralleled by lower amplitudes and longer latencies of the corresponding P3b
      ERP subcomponents. Although Tourette syndrome patients were unimpaired in overall
      performance they showed an increased interference of visual task demands with
      auditory target perception. In parallel they also exhibited a reduced amplitude
      of the P3b component to auditory targets. The findings show that Tourette
      syndrome patients are not generally impaired in their dual task performance. The
      allocation of attentional resources to competing tasks however, is altered. We
      speculate that this may be related to deficient inhibitory functions.

PMID- 11328335
TI  - Multimodal P3 under different attentional states in mesial temporal lobe
      epilepsy.
AB  - BACKGROUND: Several studies demonstrate that the P3 component of the event
      related potentials (ERP) is generated by mesial temporal structures. The P3 is
      considered as endogenous information processing component independent from
      modality. PURPOSE: The aim of this investigation was to study whether the P3
      latency elicited by auditory and visual stimuli under different attentional
      states is influenced by the mesial temporal lobe epilepsy (mTLE). METHODS: The
      event related P3 component of 10 right handed patients (7 m/3 f, mean age 31.3
      years (SD 7.3), median 31.5, range 20-47) with unilateral mTLE were studied and
      compared with 10 age matched controls (5 m/5 f, mean age 36.6 years (SD 12.6),
      median 32.1, range 22-48). Diagnosis of mTLE was based on seizure description,
      clinical history and examination, prolonged video-EEG monitoring, magnetic
      resonance imaging (MRI), interictal and ictal SPECT. P3 potentials were elicited
      with a visual and auditory three stimulus discrimination paradigm. RESULTS: The
      latency of the P3 response to the auditory stimulus under automatic and effortful
      attention was delayed (423.3 ms (SD 60.4) and 436.9 ms (SD 83.4)) compared with a
      control group (359 ms (SD 42.4) and 354.2 ms (SD 39.7); P = 0.039 and P = 0.012,
      ANOVA), while the P3 latencies to visual stimuli under both tested attentional
      states (407.3 ms (SD 52.9) and 390.6 ms (SD 40.2)) did not differ from controls
      (378.2 ms (SD 48.6) and 378.2 ms (SD 55.4)). P3 latencies to auditory novel
      paradigm in patients with right sided mTLE, but not left sided mTLE, differed
      significantly from controls (P = 0.01). CONCLUSION: The results suggest a
      modality dependence of the P3 component in patients with mTLE. The novelty
      processing of auditory stimuli is disturbed in patients with right sided mTLE.

PMID- 11328336
TI  - An ischemic stroke during intravenous recombinant tissue plasminogen activator
      infusion for evolving myocardial infarction.
AB  - A 56-year-old man without a previous history of stroke received intravenous
      recombinant tissue plasminogen activator (tPA) for an evolving myocardial
      infarction. During the infusion, the patient developed aphasia and right
      hemiparesis. The CT and MRI confirmed an ischemic stroke without evidence of
      hemorrhage. Although the cerebral hemorrhage after tPA infusion is relatively
      more common, in rare cases, tPA infusion may result in fragmentation of a cardiac
      thrombus resulting in an ischemic cerebral stroke.

PMID- 11328337
TI  - Marchiafava-Bignami disease: two cases with favourable outcome.
AB  - Marchiafava-Bignami disease (MBD) is a rare disorder of an unknown aetiology but
      strongly associated with alcoholism. MBD primarily affects the corpus callosum
      leading to confusion, dysarthria, seizures and frequently to death. Over 250
      cases from all races and from almost all nationalities have been reported, most
      cases being alcoholics. We report two cases with a favourable outcome. Magnetic
      resonance imaging (MRI) demonstrated a typical lesion of the corpus callosum, in
      both patients. The patients, a 44-year-old male and a 40-year-old female,
      presented with depressed consciousness and a variety of other symptoms, but
      finally made a reasonably good recovery leading to home discharge. To the best of
      our knowledge, only one additional case of MBD from Scandinavia has been
      published. As alcoholism is a major public health problem in Scandinavia, we
      assume that MBD is underdiagnosed and/or under-reported. Non-specific general
      symptoms and encephalopathy in an alcoholic may harbour undiagnosed MBD. We
      suggest that the incidence of MBD may be higher and its prognosis may be milder
      than generally believed.

PMID- 11328338
TI  - Diffusion-weighted magnetic resonance imaging in two patients with polycythemia
      rubra vera and early ischemic stroke.
AB  - Polycythemia rubra vera (PRV) is a rare myeloproliferative disorder with a high
      risk of ischemic stroke. Although thrombosis of large cerebral arteries is the
      most frequently presumed pathomechanism, various infarct patterns have been
      described in patients with PRV and ischemic stroke. We report two patients with
      mild acute ischemic strokes and known PRV, in whom a scattered lesion pattern was
      detected by diffusion-weighted magnetic resonance imaging (DWI), but was not
      visible on computed tomography (CT) and conventional magnetic resonance imaging
      (MRI). Further diagnostic work-up including extra- and transcranial Doppler
      sonography (ECD, TCD), transesophageal echocardiography (TEE), magnetic resonance
      angiography and Holter monitoring revealed no obvious sources of cerebral
      embolism in both cases. However, TEE in one patient demonstrated spontaneous echo
      contrast (SEC) in the left atrium. In both patients the symptomatology resolved
      completely. The detection of a scattered infarct pattern by DWI in patients with
      PRV and acute ischemic stroke has not been reported previously. DWI findings
      together with the SEC in one patient emphasize the assumption that a
      prothrombotic state with subsequent arterial embolism rather than local arterial
      thrombosis may be the underlying pathomechanism of stroke in some patients with
      PRV. Adding DWI to the diagnostic work-up may help to clarify etiology in
      patients with PRV and acute ischemic stroke.

PMID- 11328339
TI  - Rapidly progressive dementia in hypereosinophilic syndrome.

PMID- 11328340
TI  - Neuropsychological evaluation of late-onset, post-radiotherapy encephalopathy.

PMID- 11328341
TI  - Tropical pyomyositis.

PMID- 11328342
TI  - An activity-dependent switch from facilitation to inhibition in the control of
      excitotoxicity by group I metabotropic glutamate receptors.
AB  - Activation of group I metabotropic glutamate receptors (mGlu1 or -5 receptors) is
      known to either enhance or attenuate excitotoxic neuronal death depending on the
      experimental conditions. We have examined the possibility that these receptors
      may switch between two different functional modes in regulating excitotoxicity.
      In mixed cultures of cortical cells, the selective mGlu1/5 agonist, 3,5
      dihydroxyphenylglycine (DHPG), amplified neurodegeneration induced by a toxic
      pulse of NMDA. This effect was observed when DHPG was either combined with NMDA
      or transiently applied to the cultures prior to the NMDA pulse. However, two
      consecutive applications of DHPG consistently produced neuroprotection. Similar
      effects were observed with DHPG or quisqualate (a potent agonist of mGlu1/5
      receptors) in pure cultures of cortical neurons virtually devoid of astrocytes.
      In cultures of hippocampal pyramidal neurons, however, only protective effects of
      DHPG were seen suggesting that, in these particular cultures, group I mGlu
      receptors were endogenously switched into a "neuroprotective mode". The
      characteristics of the activity-dependent switch from facilitation to inhibition
      were examined in mixed cultures of cortical cells. The switch in the response to
      DHPG was observed when the two applications of the drug were separated by an
      interval ranging from 1-45 min, but was lost when the interval was extended to 90
      min. In addition, this phenomenon required the initial activation of mGlu5
      receptors (as indicated by the use of subtype-selective antagonists) and was
      mediated by the activation of protein kinase C. We conclude that group I mGlu
      receptors are subjected to an activity-dependent switch in regulating excitotoxic
      neuronal death and, therefore, the recent "history" of these receptors is
      critical for the response to agonists or antagonists.

PMID- 11328343
TI  - Nitric oxide up-regulates ferritin mRNA level in snail neurons.
AB  - We cloned and sequenced the ferric ion-binding protein, ferritin, from the
      nervous system of the pulmonate snail, Helix pomatia. Helix H-ferritin cDNA
      contains a 519-bp open reading frame (ORF) and predicts an iron-responsive
      element (IRE) at the 5'-untranslated region (5'-UTR) of the ferritin mRNA. The
      deduced amino acid sequence revealed 86% similarity with Lymnaea stagnalis
      ferritin and about 70% similarity with vertebrate H-ferritin. While secreted
      ferritin isoforms contain a signalling sequence at their N-terminal end, Helix
      ferritin does not contain this sorting signal indicating that it is restricted to
      the cytoplasm. The amino acid ligands at positions Glu25, Tyr30, Glu59, Glu60,
      His63, Glu105 and Gln139 indicate an active ferroxidase site in Helix ferritin.
      In situ hybridization visualized ferritin mRNA in neuronal cell bodies but not in
      the neuropil. In contrast, ferritin-immunoreactive protein was localized in cell
      bodies and neurites. We further demonstrate that the NO donors S-nitroso-N
      acetylpenicillamine (SNAP), or hydroxylamine (HA), increase the intracellular
      ferritin mRNA level by about 55%. In conclusion, our findings show that Helix
      neurons express an intracellular H-ferritin isoform and suggest that iron and NO
      metabolism are coupled.

PMID- 11328344
TI  - Modifications of intracellular Ca2+ signalling during nerve growth factor-induced
      neuronal differentiation of rat adrenal chromaffin cells.
AB  - Postnatal sympathetic neurons (SNs) and chromaffin cells (CCs) derive from neural
      crest precursors. CCs can differentiate in vitro into SN-like cells after nerve
      growth factor (NGF) exposure. This study examines changes of intracellular Ca2+
      homeostasis and dynamics of CCs under conditions that promote a neuronal
      phenotype. Spontaneous Ca2+ fluctuations, a frequent observation in early
      cultures of CCs, diminished after > 10 days in vitro in control cells and ceased
      in NGF-treated ones. At the same time, Ca2+ rises resulting from entry upon
      membrane depolarization, gradually increased both their size and peak
      d[Ca2+]i/dt, resembling those recorded in SNs. Concomitantly, caffeine-induced
      Ca2+ rises, resulting from Ca2+ release from intracellular stores, increased
      their size and their peak d[Ca2+]i/dt by > 1000%, and developed transient and
      sustained release components, similar to those of SNs. The transient component,
      linked to regenerative Ca2+ release, appeared after > 10 days of NGF treatment,
      suggesting a delayed steep enhancement of Ca2+-induced Ca2+ release (CICR).
      Immunostaining showed that proteins coded by the three known isoforms of
      ryanodine receptors (RyRs) are present in CCs, but that only RyR2 increased
      significantly after NGF treatment. Since the transient release component
      increased more steeply than RyR2 immunostaining, we suggest that the development
      of robust CICR requires both an increased expression of RyRs and more efficient
      functional coupling among them. NGF-induced transdifferentiation of chromaffin
      cells involves the enhancement of both voltage-gated Ca2+ influx and Ca2+ release
      from intracellular stores. These modifications are likely to complement the
      extensive morphological and functional reorganization required for the
      replacement of the endocrine phenotype with the neuronal one.

PMID- 11328345
TI  - Kindling of claustrum and insular cortex: comparison to perirhinal cortex in the
      rat.
AB  - The perirhinal cortex has recently been implicated in the kindling of limbic
      generalized seizures. The following experiments in rats tested the selectivity of
      the perirhinal cortex's epileptogenic properties by comparing its kindling
      profile with those of the adjacent insular cortex, posterior (dorsolateral)
      claustrum and amygdala. The first experiment examined the kindling and EEG
      profiles, and found that both the claustrum and insular cortex demonstrated rapid
      epileptogenic properties similar to the perirhinal cortex, including very rapid
      kindling rates and short latencies to convulsion. Furthermore, electrical
      stimulation of all three structures led to a two-phase progression through stage
      5 seizures which had characteristics of both neocortical and amygdaloid kindling.
      In a second experiment rats were suspended in a harness to allow for more
      detailed documentation of both forelimb and hindlimb convulsions. With this
      procedure we were able to detect subtle yet unique differences in convulsion
      characteristics from each of the kindled sites and stage-5 seizure phases. Some
      of these convulsive parameters were correlated with changes in FosB/DeltaFosB
      protein and BDNF mRNA expression measured two hours after the last convulsion.
      Overall, it appears that the perirhinal cortex is not unique in its property of
      rapid epileptogenesis. Moreover, the posterior claustrum exhibited the fastest
      kindling and most vigorous patterns of clonus, suggesting that it may be even
      more intimately associated with the motor substrates responsible for limbic
      seizure generalization than is the perirhinal cortex.

PMID- 11328346
TI  - For whales and seals the ocean is not blue: a visual pigment loss in marine
      mammals.
AB  - Most terrestrial mammals have colour vision based on two spectrally different
      visual pigments located in two types of retinal cone photoreceptors, i.e. they
      are cone dichromats with long-to-middle-wave-sensitive (commonly green) L-cones
      and short-wave-sensitive (commonly blue) S-cones. With visual pigment-specific
      antibodies, we here demonstrate an absence of S-cones in the retinae of all
      whales and seals studied. The sample includes seven species of toothed whales
      (Odontoceti) and five species of marine carnivores (eared and earless seals).
      These marine mammals have only L-cones (cone monochromacy) and hence are
      essentially colour-blind. For comparison, the study also includes the wolf,
      ferret and European river otter (Carnivora) as well as the mouflon and pygmy
      hippopotamus (Artiodactyla), close terrestrial relatives of the seals and whales,
      respectively. These have a normal complement of S-cones and L-cones. The S-cone
      loss in marine species from two distant mammalian orders strongly argues for
      convergent evolution and an adaptive advantage of that trait in the marine visual
      environment. To us this suggests that the S-cones may have been lost in all
      whales and seals. However, as the spectral composition of light in clear ocean
      waters is increasingly blue-shifted with depth, an S-cone loss would seem
      particularly disadvantageous. We discuss some hypotheses to explain this paradox.

PMID- 11328347
TI  - Cannabinoid receptor activation and elevated cyclic AMP reduce glutamate
      neurotoxicity.
AB  - Cannabinoid receptor activation in vivo reduces ischemic injury, a phenomenon
      that has not been successfully reproduced in vitro. Because cyclic adenosine
      monophosphate (cAMP) levels are radically elevated during ischemic reperfusion,
      but cannabinoid receptor activation reduces cAMP levels, we hypothesized that
      cannabinoids might prevent in vitro glutamate toxicity if reperfusion was
      simulated by cAMP supplementation after glutamate removal. Although neuronal
      cultures were unaffected by the single addition of either cannabinoid or
      dibutyryl cAMP (dbcAMP), glutamate toxicity was reduced by 20% when cannabinoid
      was present during glutamate exposure and either dbcAMP or forskolin was added
      after glutamate removal. Further studies revealed that cannabinoid receptor
      activation reduces glutamate toxicity by attenuating calcium influx through N-
      and P/Q-type calcium channels. The effect of glutamate exposure on neuronal cAMP
      levels was also examined. Glutamate exposure significantly reduced neuronal cAMP
      levels, although suppression was even greater when cannabinoid was present.
      Because neurological outcome after ischemia is poor when cAMP levels during
      reperfusion are low, it is hypothesized that cAMP elevation after glutamate
      exposure may offset excitotoxic and/or cannabinoid receptor-induced cAMP
      depletion. Cannabinoids protect against ischemic injury in vivo, but only reduce
      toxicity in vitro when cAMP levels are elevated, possibly suggesting that cAMP
      elevation during reperfusion reduces brain injury by off-setting the effect of
      Gi/o protein-coupled systems on adenylate cyclase.

PMID- 11328348
TI  - Contribution of intralaminar thalamic nuclei to spike-and-wave-discharges during
      spontaneous seizures in a genetic rat model of absence epilepsy.
AB  - In an epileptic rat model of generalized absence epilepsies, the genetic absence
      epilepsy rats from Strasbourg (GAERS), simultaneous recordings of bilateral
      epidural electroencephalogram (EEG) of the prefrontal cortex and unit activity of
      neurons in the intralaminar centrolateral (CL) and paracentral thalamic nucleus
      (PC) were performed under neurolept-anaesthesia (fentanyl-dehydrobenzperidol
      analgesia). Spike-and-wave (SW) seizures in these rats are characterized by
      generalized 7-10 Hz spike-and-wave discharges (SWDs) on the EEG. All neurons
      recorded in intralaminar thalamic nuclei during spontaneous SWDs showed high
      frequency (average 368 Hz, range 200-500 Hz), burst-like activity, which occurred
      in a highly synchronized fashion with every SWD or with alternating SWD
      complexes. Burst discharges in intralaminar neurons were delayed by 13.1 ms (CL)
      and 12.7 ms (PC), with respect to the spike component of a given SWD on the EEG,
      whereas burst discharges in the ventrobasal thalamus (VB) and in the rostral
      nucleus reticularis thalami (rRT) preceded the spike component by 17.8 ms and 8.3
      ms, respectively. The onset of SWDs on the EEG was preceded by a tonic firing
      pattern (20-50 Hz) in about one third of CL and PC neurons. Microiontophoretic
      application of the gamma-aminobutyric acid (GABA)A receptor antagonist
      bicuculline aggravated, whereas, the glutamate receptor antagonists DNQX and APV
      dampened, SWD-related discharges in PC and CL; the GABAB receptor antagonist CGP
      35347 had no measurable effect. These data indicate that intrathalamic nuclei are
      recruited rhythmically during SWDs, through mechanisms that seem to rely on a
      delayed glutamatergic excitation modulated by GABAergic influences, rather than a
      GABA-mediated rebound burst activity typical of relay cells. The finding of a
      temporal delay of SWD-related activity in intrathalamic, compared with "specific"
      thalamic relay nuclei, does not support the notion of a leading or pacemaker role
      in SWD generation. It is, however, rather suggestive of a function of
      intrathalamic neurons during synchronization and maintenance of neuronal
      oscillations, and these intrathalamic neurons may be recruited through
      glutamatergic corticofugal inputs.

PMID- 11328349
TI  - Multiple-site optical recording reveals embryonic organization of synaptic
      networks in the chick spinal cord.
AB  - We examined embryonic expression of postsynaptic potentials in stages 26-31 (E5
      to E7) chick spinal cord slices. Slow optical signals related to the postsynaptic
      potentials which were evoked by electrical stimulation of afferent fibers were
      identified in the dorsal grey matter and the ventral motoneuronal area. In
      cervical spinal cord (C13) preparations, the dorsal slow signal appeared from
      stage 28 (E6), whilst the ventral slow signal was recognized from stage 29. At
      stages 26 and 27 (E5), no slow signal was observed in either the dorsal or
      ventral regions. On the other hand, in lumbosacral spinal cord (LS5)
      preparations, the dorsal, as well as ventral, slow signals appeared from stage
      29; at stage 28 no slow signal was detected in the dorsal or ventral regions.
      These results suggest that there are differences in the ontogenetic expression of
      synaptic functions between the dorsal and ventral regions, and between the
      cervical and lumbosacral spinal cords. In embryos older than stage 29, removal of
      Mg2+ from the bathing solution markedly enhanced the amplitude and incidence of
      the ventral slow signal. In addition, in C13 preparations at stage 28, removal of
      Mg2+ elicited small slow signals in the ventral region in which no synaptic
      response was evoked in normal Ringer's solution. The slow signals induced in the
      Mg2+-free solution were blocked by 2-amino-5-phosphonovaleric acid (APV), showing
      that they are attributable to N-methyl- D-aspartate (NMDA) receptors. These
      results suggest that functional synaptic connections via polysynaptic pathways
      are already generated on motoneurons, but are suppressed by a Mg2+ block on the
      NMDA receptors at developmental stages when synaptic transmission from the
      primary afferents to the dorsal interneurons is initially expressed in the dorsal
      region.

PMID- 11328350
TI  - Laminar specific alterations of thalamocortical projections in organotypic
      cultures following layer 4 disruption in ferret somatosensory cortex.
AB  - The developing neocortex influences the growth of thalamocortical projections.
      Layer 4 in particular receives the majority of input from the thalamus and is
      important in instructing thalamic afferents to terminate. Previous in vivo
      experiments demonstrated that disruption of layer 4 during corticogenesis in
      ferret somatosensory cortex by application of methylazoxy methanol acetate (MAM)
      prevents proper termination of thalamic afferents in appropriate cortical
      regions. To further explore the role of layer 4 in thalamocortical development,
      we prepared organotypic cocultures consisting of normal gestational day 0 (P0)
      ferret thalamus paired with normal, embryonic day 33 (E33), or E38 MAM-treated
      cortex obtained from ferrets at either P0 or P7. Injection of MAM on E33 disrupts
      layer 4 formation, whereas similar injections on E38 interfere with layer 2
      formation. The cocultures grew together for a number of days, then discrete
      injections of either fluorescent dextrans or 1,1'-dioctadecyl-3,3,3',3'
      tetramethyl-indocarbocyanine perchlorate (DiI) were made into the thalamic piece.
      The labeled thalamic afferents that grew into the cortical slice were analysed
      and the sites of their terminations quantified after 3, 5, or 7-10 days in
      culture (DIC). Our results varied somewhat with the amount of time in culture,
      but the preponderance of thalamic fibers in normal cortex terminated in layer 4,
      whereas their counterparts in E33 MAM-treated cortex grew beyond the cortical
      plate and many fibers terminated inappropriately within lower cortical layers or
      white matter. Terminal distribution of thalamic fibers in E38 MAM-treated cortex
      looked similar to normal. These results demonstrate that the cells of layer 4
      provide thalamic afferents with important positional and termination cues.

PMID- 11328351
TI  - The cortical connections of area V6: an occipito-parietal network processing
      visual information.
AB  - The aim of this work was to study the cortical connections of area V6 by
      injecting neuronal tracers into different retinotopic representations of this
      area. To this purpose, we first functionally recognized V6 by recording from
      neurons of the parieto-occipital cortex in awake macaque monkeys. Penetrations
      with recording syringes were performed in the behaving animals in order to inject
      tracers exactly at the recording sites. The tracers were injected into the
      central or peripheral field representation of V6 in different hemispheres.
      Irrespective of whether injections were made in the centre or periphery, area V6
      showed reciprocal connections with areas V1, V2, V3, V3A, V4T, the middle
      temporal area /V5 (MT/V5), the medial superior temporal area (MST), the medial
      intraparietal area (MIP), the ventral intraparietal area (VIP), the ventral part
      of the lateral intraparietal area and the ventral part of area V6A (V6AV). No
      labelled cells or terminals were found in the inferior temporal, mesial and
      frontal cortices. The connections of V6 with V1, and with all the retinotopically
      organized prestriate areas, were organized retinotopically. The connection of V6
      with MIP suggests a visuotopic organization for this latter. Labelling in V6A and
      VIP after either central or peripheral V6 injections was very similar in location
      and extent, as expected on the basis of the nonretinotopic organization of these
      areas. We suggest that V6 plays a pivotal role in the dorsal visual stream, by
      distributing the visual information coming from the occipital lobe to the
      sensorimotor areas of the parietal cortex. Given the functional characteristics
      of the cells of this network, we suggest that it could perform the fast form and
      motion analyses needed for the visual guiding of arm movements as well as their
      coordination with the eyes and the head.

PMID- 11328352
TI  - Delayed infusion of GDNF promotes recovery of motor function in the partial
      lesion model of Parkinson's disease.
AB  - Here we studied the effects of glial cell line-derived neurotrophic factor (GDNF)
      in a rat model that represents the symptomatic stages of Parkinson's disease.
      GDNF was infused starting 2 weeks after an intrastriatal 6-hydroxydopamine (6
      OHDA) lesion in order to halt the ongoing degeneration of the nigrostriatal
      dopaminergic neurons. GDNF or vehicle was infused in the striatum or the lateral
      ventricle via an osmotic minipump over a total 4-week period (2-6 weeks
      postlesion). Motor function was evaluated by the stepping, paw reaching and drug
      induced motor asymmetry tests before the pump infusion was initiated, and was
      repeated once during (5 weeks postlesion) and twice after the withdrawal of the
      minipumps (7 and 11 weeks postlesion). We found that within two weeks following
      the lesion approximately 40% of the nigral TH-positive neurons were lost. In the
      vehicle infusion groups there was an additional 20% cell loss between 2 and 12
      weeks after the lesion. This latter cell loss occurred mainly in the caudal part
      of the SN whereas the cell loss in the rostral SN was almost complete within the
      first two weeks. Ventricular GDNF infusion completely blocked the late
      degenerating neurons in the caudal SN and had long lasting behavioural effects on
      the stepping test and amphetamine rotation, extending to 6 weeks after withdrawal
      of the factor. Striatal infusion affected the motor behaviour transiently during
      the infusion period but the motor performance of these animals returned to
      baseline upon cessation of the GDNF delivery, and the delayed nigral cell loss
      was marginally affected. We conclude that intraventricular GDNF can successfully
      block the already initiated degenerative process in the substantia nigra, and
      that the effects achieved via the striatal route, when GDNF is given acutely
      after the lesion, diminish as the fibre terminal degeneration proceeds.

PMID- 11328353
TI  - Immunohistochemical characterisation of Fos-positive cells in brainstem
      monoaminergic nuclei following intracranial self-stimulation of the medial
      forebrain bundle in the rat.
AB  - Fos immunostaining was used as a marker of neuronal activity following
      intracranial self-stimulation (ICSS) of the medial forebrain bundle (MFB) in the
      rat, and was combined with immunostaining for tyrosine hydroxylase (TH),
      serotonin (5-HT), gamma-aminobutyric acid (GABA), or NR1 (one of the glutamate N
      methyl- D-aspartate receptor subunits) for purposes of neurochemical
      identification. ICSS induced a significant but different degree of increase in
      the number of Fos-immunopositive (Fos+) cells in the six brainstem monoaminergic
      nuclei examined, which included the ventral tegmental area (VTA), substantia
      nigra pars compacta (SNc), dorsal raphe nucleus (DR), median raphe nucleus (MR),
      locus coeruleus (LC), and A7 noradrenaline cells. Densely labelled Fos+ cells
      were observed in the LC following ICSS, and many of these Fos+ cells were
      colocalized with TH. Similarly, many of Fos+ cells in the A7 and DR/MR were
      colocalized with TH and 5-HT, respectively. By contrast, a smaller number of Fos+
      cells was detected in the VTA and SNc following the ICSS, and in these regions
      the majority of Fos+ cells were not colocalized with TH. Although results among
      regions quantitatively differed, the ICSS induced a significant increase in the
      number of double-labelled cells (GABA+/Fos+ or NR1+/Fos+) in all of the VTA, DR,
      and LC, in which the ICSS produced an ipsilaterally weighted increase in Fos-like
      immunoreactivity. These results suggest that ICSS of the MFB induces differential
      Fos expression within monoaminergic and GABAergic neurons in brainstem
      monoaminergic nuclei under modulation by glutamatergic afferents.

PMID- 11328354
TI  - Effects of STN lesions on simple vs choice reaction time tasks in the rat:
      preserved motor readiness, but impaired response selection.
AB  - The subthalamic nucleus (STN) is a key structure within the basal ganglia,
      inactivation of which is a current strategy for treating parkinsonism. We have
      previously shown that bilateral lesions of the STN or pharmacological
      inactivation of this structure in the rat induce multiple deficits in serial
      reaction time tasks. The aim of the present study was to investigate further a
      possible role for the STN in response preparatory processes by using simple (SRT)
      and choice (CRT) reaction time tasks. In contrast to the CRT procedure, the
      information related to the location of where the response had to be made was
      given in advance in the SRT procedure. Accurate performance on these tasks
      requires not only the selection of the correct response (i.e. which response),
      but also preparation in order to perform when required. A comparison between the
      two tasks allows assessment of whether STN lesions affect which response
      ("which") or when to perform it ("when"). As previously observed in these
      procedures, the responses were faster as a function of the variable foreperiod
      preceding the trigger stimulus. This well-known effect, termed "motor readiness,
      was maintained after STN lesions, suggesting that STN lesions did not affect the
      "when" phase of action preparation. However, while performance on the SRT was
      faster than on the CRT task preoperatively, STN lesions slowed RTs and abolished
      the beneficial effect of advance information, suggesting a deficit in the
      selection ("which") phase of response preparation. This deficit in the selection
      phase was further supported by deficits in accuracy of responding after STN
      lesions, as well as increases in mislocated premature responding in the SRT
      condition. Together, these results suggest that the STN plays an important role
      in response preparatory processes, including response selection and inhibitory
      control processes.

PMID- 11328355
TI  - Hippocampus and homing in pigeons: left and right hemispheric differences in
      navigational map learning.
AB  - One-month-old, inexperienced homing pigeons, prior to any opportunity to learn a
      navigational map, were subjected to either right or left unilateral ablation of
      the hippocampal formation (HF). These pigeons were then held together with a
      group of age-matched control birds in an outdoor aviary, where they were kept for
      about 3 months with the opportunity to learn a navigational map. When
      subsequently tested for navigational map learning at about 4 months of age
      posthatching, control and right HF-ablated pigeons were equally good at orienting
      homeward from distant, unfamiliar locations, indicating successful navigational
      map learning. By contrast, left HF-ablated pigeons were impaired in orienting
      homeward, indicating a failure to learn a navigational map. Interestingly, both
      right and left HF-ablated pigeons displayed impaired homing performance relative
      to controls. These results suggest that different aspects of homing pigeon
      navigation may be lateralized to different hemispheres, and in particular, the HF
      of the different hemispheres. The left HF appears critical for navigational map
      learning, i.e. determining an approximate direction home from distant, unfamiliar
      locations. The right HF, and possibly the left HF as well, appear to play an
      important role in local navigation near the loft, which is likely based on
      familiar landmarks.

PMID- 11328356
TI  - Behavioural profiling of a murine Charcot-Marie-Tooth disease type 1A model.
AB  - Different features of motor behaviour were studied on a transgenic mouse model of
      Charcot-Marie-Tooth's disease (CMT). Mutants with 4 or 7 copies of the human
      PMP22 gene leading to a phenotype significantly close to CMT's disease type 1A
      were compared with control animals. The aim of the study was to validate this
      transgenic model and to characterise the impairments occurring in the various
      lines. Three main types of analysis were performed in 2-month-old mice without
      any peculiar visible deficit: (i) a study of standardised clinical tests (SHIRPA
      protocol) demonstrated that only a few motor deficits were expressed; (ii) a
      measurement of general spontaneous activity by means of a commercial video
      tracking system was performed and revealed that the main spontaneous activities
      were identical in the three lines with, however, some slight localised
      modifications; and, (iii) by contrast, the three lines respond very differently
      to the footprints, grip strength, splay test and rotarod test. Even in lines with
      a significantly limited copy number of the transgene, we observed and quantified
      impairments. In conclusion, mutants of CMT1A seem to be a very pertinent model of
      this human pathology and will certainly be useful for therapeutic procedures and
      for theoretical studies on this disease.

PMID- 11328357
TI  - Sindbis viral-mediated expression of Ca2+-permeable AMPA receptors at hippocampal
      CA1 synapses and induction of NMDA receptor-independent long-term potentiation.
AB  - Gene manipulation in order to artificially express a particular gene in neurons
      in the central nervous system is a powerful tool for the analysis of brain
      function. Sindbis viral vectors have been developed to express high levels of
      foreign genes in postmitotic brain neurons with little transfection of glial
      cells. In this study, we expressed the gene encoding the unedited GluR2 (GluR-B)
      subunit of the AMPA-type glutamate receptor that forms inwardly rectifying and
      Ca2+-permeable channels, in rat CA1 hippocampal neurons in slice cultures using
      Sindbis viral vectors. The pyramidal cell layer of the CA1 region was injected
      with recombinant Sindbis viruses encoding both enhanced green fluorescent protein
      (GFP) and unedited GluR2. The GFP fluorescence from CA1 neurons could be detected
      as early as 6 h and reached a maximal level about 48 h postinfection. The
      inwardly rectifying and Ca2+-permeable AMPA receptors were expressed in most CA1
      pyramidal cells expressing GFP. These AMPA receptors expressed by gene transfer
      were involved in fast excitatory neurotransmission elicited by electrical
      stimulation of the Schaffer collaterals in the stratum radiatum. Tetanic
      stimulation of Schaffer collaterals induced NMDA receptor-independent, long-term
      potentiation due to Ca2+ influx through the newly expressed AMPA receptors in the
      area densely stained with GFP. Thus, the combined use of Sindbis viral vectors
      with the GFP reporter allowed physiological examination of the roles of a
      specific gene product in synaptic function in well-characterized brain neurons.

PMID- 11328359
TI  - Neural correlates of religious experience.
AB  - The commonsense view of religious experience is that it is a preconceptual,
      immediate affective event. Work in philosophy and psychology, however, suggest
      that religious experience is an attributional cognitive phenomenon. Here the
      neural correlates of a religious experience are investigated using functional
      neuroimaging. During religious recitation, self-identified religious subjects
      activated a frontal-parietal circuit, composed of the dorsolateral prefrontal,
      dorsomedial frontal and medial parietal cortex. Prior studies indicate that these
      areas play a profound role in sustaining reflexive evaluation of thought. Thus,
      religious experience may be a cognitive process which, nonetheless, feels
      immediate.

PMID- 11328358
TI  - Protein kinase Calpha and beta1 isoforms are regulators of alpha-secretory
      proteolytic processing of amyloid precursor protein in vivo.
AB  - We have recently shown that in utero treatment of guinea pigs with the DNA
      methylating substance methylazoxymethanol acetate (MAM) results in neocortical
      microencephalopathy, increased protein kinase C (PKC) activity and altered
      processing of the amyloid precursor protein (APP) in neocortex of offspring. Here
      we show that PKCalpha and PKCbeta1 are the key regulators of alpha-secretory APP
      processing in guinea pig neocortex under these experimental conditions in vivo.
      This conclusion is based on the selective translocation of PKCalpha and PKCbeta1
      isoforms to the cell membrane in MAM-treated guinea pigs, as revealed by Western
      blot analysis and by immunocytochemistry. Additionally, we observed that
      [3H]phorbol ester binding to protein kinase C increased by 38% and enhanced basal
      PKC activity by 58% in the neocortex of microencephalic guinea pigs. Inhibition
      of PKCalpha/PKCbeta1 by Go6976 abolished this difference, suggesting that
      constitutive overactivation of these PKC isoforms accounts for the increase in
      total PKC activity. We also observed a strong positive correlation between levels
      of alpha-secretase-processed APP and PKC activity in the neocortex of individual
      animals, providing further evidence for a significant role of classical PKC
      isoforms in nonamyloidogenic APP processing.

PMID- 11328360
TI  - Helicobacter pylori infection in the cat: evaluation of gastric colonization,
      inflammation and function.
AB  - BACKGROUND: Further elucidation of the consequences of Helicobacter pylori
      infection on gastric mucosal inflammation and gastric secretory function would be
      facilitated by an animal model that is susceptible to infection with H. pylori,
      is broadly similar in gastric physiology and pathology to people, and is amenable
      to repeated non-invasive evaluation. The goal of this study was to examine the
      interrelationship of bacterial colonization, mucosal inflammation and gastric
      secretory function in cats with naturally acquired H. pylori infection. MATERIALS
      AND METHODS: Twenty clinically healthy cats with naturally acquired H. pylori
      infection (cagA-, picB) and 19 Helicobacter-free cats were evaluated. Gastric
      colonization was determined by tissue urease activity, light microscopy, culture
      and PCR. The mucosal inflammatory response was evaluated by light microscopy, and
      by RT-PCR of the pro-inflammatory cytokines IL-1alpha, IL-1beta, IL-8 and TNF
      alpha in gastric mucosa. Gastric secretory function was assessed by measuring
      pentagastrin-stimulated acid secretion, fasting plasma gastrin, and antral
      mucosal gastrin and somatostatin immunoreactivity. RESULTS: H. pylori colonized
      the pylorus, fundus and cardia in similar density. Bacteria were observed free in
      the lumen of gastric glands and were also tightly adherent to epithelial cells
      where they were associated with microvillus effacement. Mononuclear inflammation,
      lymphoid follicle hyperplasia, atrophy and fibrosis were observed primarily in H.
      pylori-infected cats, with the pylorus most severely affected. Neutrophilic and
      eosinophilic infiltrates, epithelial dysplasia, and up-regulation of mucosal IL
      1beta and IL-8 were observed solely in infected cats. Fasting plasma gastrin
      concentrations and pentagastrin-stimulated acid output were similar in both
      infected and uninfected cats. There was no relationship of bacterial colonization
      density or gastric inflammation to plasma gastrin concentrations or gastric acid
      output. CONCLUSIONS: The pattern of colonization and the mucosal inflammatory
      response in cats with naturally acquired H. pylori are broadly similar to those
      in infected people, particularly children, and non-human primates. The
      upregulation of IL-8 in infected cats was independent of cagA and picB. Our
      findings argue against a direct acid-suppressing effect of H. pylori on the
      gastric secretory-axis in chronically infected cats.

PMID- 11328361
TI  - New approaches for validation of lethal phenotypes and genetic reversion in
      Helicobacter pylori.
AB  - BACKGROUND: Because of limited genetic tools for use in Helicobacter pylori,
      tests routinely applied in other bacteria for demonstrating a gene's role in
      viability and other phenotypes have not been applied to this organism. In a
      mutational study of putative response regulator genes, we aimed to develop such
      tools for H. pylori. MATERIALS AND METHODS: We attempted to mutate five response
      regulator genes by allelic exchange insertional mutagenesis. For genes that
      yielded no viable mutants, a second copy of the gene was inserted into the
      chromosome via a suicide vector, and it was seen if providing the second copy
      would permit the gene's disruption. For genes that yielded mutants with
      selectable phenotypes, a strategy was developed for reversion whereby an intact
      copy of the gene is introduced to the organism by transformation with PCR
      products. Following this procedure, revertants were selected by phenotypic tests
      then tested for genetic reversion. RESULTS: After failure to attain transformants
      upon attempted mutation of genes HP0166 and HP1365, we inserted a second copy of
      each gene within the H. pylori chromosome. In each case the second copy relieved
      the block of transformation. Mutation of genes HP0703 and HP1021 gave non-motile
      and small-colony phenotypes, respectively. Following transformation with PCR
      products containing intact copies of the genes, both phenotype and genotype had
      reverted following phenotypic selections. CONCLUSIONS: The methods used in this
      study provide new approaches for confirming suspected genotype/phenotype
      associations and should be widely applicable in the study of H. pylori.

PMID- 11328362
TI  - The accuracy of serologic diagnosis of Helicobacter pylori infection in school
      aged children of mixed ethnicity.
AB  - The present study evaluated two non-invasive diagnostic methods for H. pylori
      infection in children, i.e. an in-house ELISA using sonicated Campylobacter
      jejuni antigen for absorption of cross-reacting antibodies and an immunoblot kit
      (Helico Blot 2.0, Genelabs, Singapore). 13C -Urea breath test (13C-UBT) was used
      as reference METHOD: Sera and questionnaires were collected from 695/858 (81%)
      Swedish school children with mixed ethnic backgrounds within a cross-sectional,
      community-based study. Of 133 children with an ELISA OD value of > or = 0.1, all
      were screened with immunoblot and 107 made a 13C-UBT. The negative controls were
      34/37 children from three school classes with an ELISA OD value of < 0.1 and
      volunteering for a 13C-UBT. An adjusted cut-off level for the ELISA of OD value
      0.22 resulted in a sensitivity of 97.8%, a specificity of 95.8% and a concordance
      index of 97.2%. The Helico Blot 2.0 had a sensitivity of 97.8%, a specificity of
      93.8% and a concordance index of 96.5%. The best concordance was seen for the
      26.5 kDa (98.6%), 30 kDa (95.7%) and 19.5 kDa (91.5%) antigens. The corresponding
      concordance index for CagA was 78%, for VacA 73.8% and for the 35kDa antigen
      68.8%. A significant difference in the distribution of the 19.5 and 26.5 kDa
      bands but not of CagA/VacA was noted by ethnic background. With an adjusted cut
      off level for the enzyme-linked immunosorbent assay (ELISA), both non-invasive
      methods were found to have an adequate performance in a pediatric population. The
      differences in antibody response patterns by ethnic background represent a caveat
      in the interpretation of serological studies.

PMID- 11328363
TI  - p53 expression in the gastric mucosa before and after eradication of Helicobacter
      pylori.
AB  - BACKGROUND: Accumulation of p53 has been recognized in the gastric mucosa
      infected with Helicobacter pylori. We investigated the prevalence of p53-positive
      cells in the gastric mucosa before and one month after eradication of H. pylori
      and the relationship between p53 positivity and inflammation and cell
      proliferation. METHODS: The subjects included 24 H. pylori-positive patients.
      They achieved eradication one month after anti-H. pylori therapy. Biopsies were
      taken from the greater curvatures of the antrum and middle body. H. pylori status
      was assessed using culture and tissue section (Giemsa stain). Serial sections
      were used for examination of gastritis (hematoxylin and eosin stain) and for
      immunostaining of p53, Ki-67 and myeloperoxidase (MPO). p53 index and Ki-67
      labeling index (LI) were calculated by counting p53-positive and Ki-67-positive
      cells in the entire gastric pits longitudinally sectioned and expressing them as
      a percentage of the total cells in a gastric pit. In the neck regions with and
      without p53-positive cells, polymorphonuclear leukocytes (PMNs) were counted in
      the corresponding area (/50 x 50 microm2) of the sections stained both with p53
      and MPO. RESULTS: p53-positive cells decreased significantly after eradication of
      H. pylori. Before eradication, the number of PMNs was significantly higher in the
      neck regions with p53-positive cells than in those without. CONCLUSIONS: In the
      gastric mucosa infected with H. pylori, p53-positive cells were found in the neck
      region infiltrated with PMNs. p53 expression decreased significantly one month
      after eradication of H. pylori.

PMID- 11328364
TI  - Inducible nitric oxide synthase expression in gastroduodenal diseases infected
      with Helicobacter pylori.
AB  - BACKGROUND: Nitric oxide (NO) is synthesized enzymatically from L-arginine by NO
      synthase, which is measured by inducible NO synthase (iNOS). Helicobacter pylori
      (H. pylori) infection produces a state of chronic immunostimulation in the
      gastric epithelium. Infection with cagA+ H. pylori has greater degree of gastric
      inflammation and epithelial cell damage. Therefore, we compared the levels of
      iNOS in patients with H. pylori infection in relation to cagA status and H.
      pylori-related disease. MATERIALS AND METHODS: One hundred and seven patients,
      including 51 patients with gastric cancer, 12 patients with gastric ulcer, 18
      patients with duodenal ulcer and 26 patients with chronic gastritis, were
      enrolled in this study. Biopsies from the antrum and body were obtained for
      histologic examination, culture and reverse transcriptionase-PCR (RT-PCR) for
      detection of iNOS gene expression. The presence of H. pylori was confirmed by
      Giemsa staining or culture and the gene expression of cagA in H. pylori isolates
      was confirmed by PCR. RESULTS: H. pylori infection was detected in 70.1% (75/107)
      and cagA was detected in 84.8% (28/33). iNOS expression was detected in 49.5%
      (53/107) and there was no significant difference in iNOS expression according to
      H. pylori infection nor the cagA status in the gastroduodenal diseases. However,
      iNOS expression was more frequently detected in gastric cancer than the other H.
      pylori-related diseases (64.7% vs. 35.7%, p <.05). CONCLUSION: Although NO was
      thought be involved in the gastric carcinogenesis, the level of NO production was
      not related to H. pylori infection or cagA status.

PMID- 11328365
TI  - The 26-kilodalton, AhpC homologue, of Helicobacter pylori is also produced by
      other Helicobacter species.
AB  - BACKGROUND: The 26 kDa protein, which is an alkyl hydroperoxide reductase (AhpC)
      homologue, has earlier been described as specific for Helicobacter pylori. The
      aims of this study were to analyse whether this protein, or the corresponding
      gene, could be identified in other Helicobacter species. MATERIALS AND METHODS:
      Two different monoclonal antibodies (Mabs), which recognise the 26 kDa protein in
      H. pylori, were used in immunoblots to determine the presence of the protein in
      10 Helicobacter species. PCR was performed in order to analyse whether the gene
      was detectable and the PCR products were sequenced. Southern and Northern blot
      analyses were done on chromosomal DNA and total RNA, respectively, isolated from
      some selected Helicobacter species in order to compare the genes and mRNA
      transcripts to H. pylori. RESULTS: The 26 kDa protein was identified in H.
      nemestrinae (primate), H. acinonychis (cheetah), H. bilis (mouse), H. felis (cat)
      and H. salomonis (dog) but not in H. mustelae (ferret), H. cinaedi (human), H.
      canis (dog), H. fennelliae (human) or H. pullorum (poultry). By PCR the gene was
      also recognised in H. mustelae, H. cinaedi and H. pullorum. The PCR products
      showed high sequence homology (66-98%) compared to H. pylori. The gene was also
      highly conserved in four H. pylori strains (94-99% homology). Southern blot
      showed that the H. nemestrinae and H. acinonychis chromosomal DNA contained a
      single copy of the gene and the Northern blot analyses indicated mono-cistronic
      transcription of the gene in these two species, as has been found in H. pylori.
      CONCLUSIONS: A gene similar to ahpC was found in eight out of 10 Helicobacter
      species analysed.

PMID- 11328366
TI  - A possible relation of the Helicobacter pylori pfr gene to iron deficiency
      anemia?
AB  - BACKGROUND: H. pylori infection is thought to contribute to iron-deficiency
      anemia, especially during puberty. The ferritin protein Pfr of H. pylori is
      homologous to eukaryotic and prokaryotic ferritins. The purpose of this study was
      to analyze the H. pylori pfr status in gastric biopsy specimens according to
      clinical data, including antral gastritis with or without iron-deficiency anemia.
      METHODS: A total of 26 H. pylori-positive patients aged from 10-18 years were
      categorized into subgroups based on the presence or absence of iron-deficiency
      anemia. All of them had antral gastritis. Sixteen patients were proved to have
      iron-deficiency anemia by hematological study, two of which had a duodenal ulcer.
      The other 10 patients showed normal hematological findings. DNA isolation was
      performed from each of the gastric biopsy specimens. PCR amplification of the pfr
      gene coding was done using two sets of primers. The pfr region, 501 bp, was
      generated by linking the sequences of the two PCR products. The nucleotide and
      protein sequences were compared between the pfr regions from Korean H. pylori
      strains and the NCTC 11638 strain, which was obtained from the Genbank. Sequence
      comparisons were also performed for the pfr regions between the iron-deficiency
      anemia (+) and (-) groups. RESULTS: Analysis of the complete coding region of the
      pfr gene revealed three sites of mutation. The Ser39Ala mutation was found in
      100% (26/26), Gly111Asn in 26.9% (7/26), and Gly82Ser in 11.5% (3/26). There were
      no significant differences in the mutations of the pfr regions between the iron
      deficiency anemia (+) and (-) groups. CONCLUSION: The mutation in the pfr gene
      did not relate with the clinical phenotype, iron deficiency anemia. Further
      studies are needed on the aspects of host side or other complex factors to
      elucidate the mechanisms by which the H. pylori infection might lead to iron
      deficiency anemia.

PMID- 11328367
TI  - Beneficial effect of Helicobacter pylori eradication in dermatologic diseases.
AB  - BACKGROUND: A relationship between skin diseases, particularly rosacea and
      chronic urticaria, and H. pylori infection has been suggested. METHODS: We
      preformed a prospective evaluation of the effect of H. pylori eradication in
      patients with a variety of chronic skin diseases. Patients were followed monthly
      for at least one year after cure of the infection. The effect of therapy was
      scored using a three point scale: complete remission (> 90% improvement), partial
      remission (50-90% improvement) or no improvement (< 50 improvement). The
      relationship between response and anti-H. pylori Ig G and E to specific H. pylori
      antigens was analyzed by Western blot analysis. RESULTS: Eighty-eight H. pylori
      infected patients with skin disease were enrolled. Treatment was successful in
      73% of patients with chronic urticaria as 23% (6 of 26) had complete and 50% had
      partial remission. Sixty-two percent (18 of 29) with pruritus cutaneus had
      partial remission as well as 30% with prurigo chronica multiformis had complete
      remission. Western blotting was done on 24 patients with skin disease and a 44K
      H. pylori antigen was detected by Ig E analysis in 100% (5 of 5) patients with
      complete remission compared to 23% (3 of 13) in those without skin disease.
      CONCLUSIONS: These results suggest it may be prudent to test patients with
      chronic urticaria, prurigo chronica multiformis, pruritus cutaneus, and eczema
      nummulare for H. pylori infection and to eradicate the infection in those whose
      test is positive.

PMID- 11328368
TI  - Costs of managing Helicobacter pylori-infected ulcer patients after initial
      therapy.
AB  - BACKGROUND: The objective of this research was to evaluate the outcomes and costs
      of alternative approaches to managing patients previously treated for peptic
      ulcer disease and Helicobacter pylori infection. MATERIALS AND METHODS: A
      decision-analytic model was used to compare (1a) urease breath testing (UBT) for
      assessment of H. pylori status versus (1b) observation without further testing or
      treatment, among patients who were symptom-free following initial antimicrobial
      and antisecretory therapy for endoscopically demonstrated ulcer and H. pylori
      infection; and (2a) UBT versus (2b) repeat endoscopy with H. pylori testing, and
      versus (2c) repeat antimicrobial and antisecretory therapy without further
      testing, among patients who remained symptomatic following initial therapy.
      RESULTS: Among patients who were symptom free after initial therapy, 6.1%
      receiving UBT had symptomatic ulcer at one year, compared to 18.2% of those
      simply observed. The expected first-year cost per symptom-free patient following
      initial therapy was $591 for UBT compared to $480 for observation. Among patients
      with persistent symptoms after initial therapy, 21% receiving repeat therapy had
      symptomatic ulcer at one year, compared to 23.8% receiving repeat endoscopy, and
      23.3% receiving UBT. Corresponding medical costs per patient were, respectively,
      $766, $1787 and $1122. CONCLUSIONS: The optimal approach to managing patients
      following initial treatment for ulcer and H. pylori infection depends on symptom
      status following initial therapy. For symptomatic patients, the preferred
      approach is to prescribe a repeat course of antimicrobial and antisecretory
      therapy. For patients without symptoms following initial therapy, UBT is the
      preferred approach because it is associated with a threefold lower risk of
      symptomatic ulcer at one year, although it costs an additional $110 per patient,
      compared with observation.

PMID- 11328369
TI  - Helicobacter pylori and altered parietal cell morphology and function.

PMID- 11328370
TI  - Stable amoxicillin resistance in Helicobacter pylori.

PMID- 11328371
TI  - Mature T cell seeks antigen for meaningful relationship in lymph node.

PMID- 11328372
TI  - Perpetuation of immunological memory: a relay hypothesis.
AB  - A mechanism is proposed which explains the perpetuation of B-cell immunological
      memory indefinitely without requiring the presence of long-living memory cells or
      persisting antigen. The salient feature of this model is that immunological
      memory can be perpetuated indefinitely through the mutual interaction of
      idiotypic and anti-idiotypic B cells. These cells mutually stimulate and clonally
      expand with either specific or bystander T-cell help. Because B cells can present
      antigen, they present 'apparently foreign' idiopeptides to T cells. The
      idiopeptides of de novo synthesized antibody is presented to CD8+ T cells that
      recognize the idiopeptide-presenting cell as targets and regulate their
      population. The recycling of immunoglobulins from surface to endosomal
      compartment of B cells leads to the presentation of idiopeptides by major
      histocompatibility complex (MHC) class II to CD4+ T cells. Even if the majority
      of the clonally expanded cells die because of lack of stimulation, cytotoxic T
      lymphocyte (CTL) lysis or for other reasons, the surviving cells will be able to
      carry forward the memory. This mechanism also provides a means for affinity
      maturation through idiotypic selection of somatically mutated high affinity cells
      or those from the naive pool. We have termed these two types of complementary B
      cells as Burnet B cells: those which recognize the antigen or antigen mimic, and
      Jerne B cells, which can recognize the idiotypes of antibody and carry antigen
      mimics. The proposed hypothesis can explain differential duration of memory for
      different antigens, the shelf space paradox, affinity maturation, repertoire
      shift, etc.

PMID- 11328373
TI  - Functional and phenotypic characterization of distinct porcine dendritic cells
      derived from peripheral blood monocytes.
AB  - Dendritic cells (DCs) are bone marrow-derived antigen-presenting cells that have
      an exquisite capacity to interact with T cells and modulate their responses.
      Little is known about porcine DCs despite the fact that they represent an
      important target in strategies that are aimed at modulating resistance to
      infection in pigs and may be of major importance in transplantation biology. We
      generated immature monocyte-derived porcine dendritic cells (MoDCs) directly from
      adherent peripheral blood cells treated with porcine granulocyte-macrophage
      colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4). The cells were
      observed via electron microscopy and their phenotype was characterized using
      monoclonal antibodies. The functionality of the porcine MoDCs was demonstrated
      showing that the cells were capable of different specialized functions relevant
      to antigen capture and were potent stimulators in a primary allo-mixed leucocyte
      reaction. Treatment of the MoDCs with porcine cell line-derived necrotic factors
      resulted in the phenotypic and functional maturation of MoDCs. We confirmed also
      that monocyte-derived DCs were differentially regulated by cytokines, showing
      that transforming growth factor-beta1 (TGF-beta1) is able to redirect monocytic
      precursors into the differentiation pathway of Langerhans' cells presenting
      typical Birbeck granules. Interestingly, and in contrast to the human and murine
      model, we showed that the monocyte-derived porcine Langerhans'-type cells (MoLCs)
      were much more potent activators of allogeneic T cells than MoDCs obtained
      without TGF-beta1.

PMID- 11328374
TI  - Introducing endogenous antigens into the major histocompatibility complex (MHC)
      class II presentation pathway. Both Ii mediated inhibition and enhancement of
      endogenous peptide/MHC class II presentation require the same Ii domains.
AB  - The invariant chain (Ii) plays a key role in regulating the antigen presentation
      function of major histocompatibility complex (MHC) class II molecules. Ii also
      influences the presentation of usually excluded endogenously synthesized proteins
      into the MHC class II presentation pathway. To evaluate the role of Ii in the
      generation of peptide-MHC class II complexes derived from endogenously
      synthesized proteins, we tested mutant Ii constructs in two model systems. Co
      expression of wild-type Ii inhibits the presentation of hen-egg lysozyme (HEL) 35
      45/Ak complex, but enhances the presentation of ovalbumin (OVA) 247-265/Ak
      complex from endogenously synthesized HEL or OVA precursors. The differential
      sensitivity of these antigens to chloroquine was consistent with their being
      processed in distinct compartments. Nevertheless, with a panel of Ii deletion
      constructs we show here that both the Ii-mediated inhibition and enhancement
      functions require the endosomal targeting and CLIP residues. Surprisingly, the Ii
      mutant lacking the endoplasmic reticulum lumenal residues 126-215, despite
      apparently lower expression, was at least as effective as full-length Ii in
      antigen presentation assays. Thus, alternative pathways exist for processing
      endogenously expressed antigens, and Ii-mediated inhibition and enhancement of
      peptide/MHC class II expression depend upon the same regions, with neither
      requiring the 89 C-terminal, lumenal Ii residues.

PMID- 11328375
TI  - Integrating signals from T-cell receptor and serum by T cells enhance translation
      of tumour necrosis factor-alpha.
AB  - Tumour necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine produced
      by several cell types, including T cells upon antigen stimulation. Its production
      is crucial for the development of an early defence against many pathogens, but
      its beneficial effects are dependent on the strength and duration of its
      expression. In this paper we present evidence indicating that serum increases
      translational efficiency of TNF-alpha in human peripheral blood mononuclear cells
      stimulated with superantigen. The increase in translation of TNF-alpha due to
      serum could be inhibited by the phosphatidylinositol (PI) 3-K inhibitors,
      wortmannin and LY294002, suggesting that PI 3-K is involved in the translational
      control of TNF-alpha by serum. Similarly to primary T cells, stimulation of
      Jurkat T cells with superantigen led to TNF-alpha secretion and this was up
      regulated by serum. Transfection of Jurkat cells with a constitutively active
      form of PI 3-Kalpha increased the production of TNF-alpha in cells stimulated
      with superantigen. Additionally, we used the specific inhibitors targeting ERK
      kinase and p38 mitogen-activated protein kinase (MAPK), potentially downstream of
      PI 3-kinase, PD98059 and SB203580. Differently from with PI 3-K inhibitors, the
      accumulation of TNF-alpha mRNA was inhibited by PD98059 or SB203580. These
      results suggest that, in T cells, activation of PI 3-K is an important step in
      controlling TNF-alpha protein synthesis in response to growth factors.

PMID- 11328376
TI  - Long-term in vivo depletion of functional CD4+ T lymphocytes from calves requires
      both thymectomy and anti-CD4 monoclonal antibody treatment.
AB  - In vivo depletion of lymphocyte subsets is a direct approach used for dissection
      of the mechanisms of protective immunity. Long-term in vivo depletion of bovine T
      lymphocyte subpopulations with monoclonal antibody (mAb) treatment alone has been
      difficult to achieve. The objective of this study was to determine whether both
      thymectomy and anti-CD4 mAb treatment would optimize long-term in vivo depletion
      of functional bovine CD4+ T lymphocytes. Calves were thymectomized and treated
      with high doses of anti-CD4 mAb (approximately 5 mg/kg) over 4 days followed by
      subsequent lower doses (approximately 0.3 mg/kg) administered twice weekly for an
      additional 7 weeks. Depletion of CD4+ T lymphocytes from blood, spleen and
      peripheral lymph nodes was significantly improved in thymectomized calves
      compared to thymus-intact anti-CD4 mAb-treated calves. Significant differences in
      percentages of CD4+ T lymphocytes between thymectomized and thymus-intact calves
      were sustained for the duration of the 8-week study. Depletion of CD4+ T
      lymphocytes from thymectomized calves resulted in complete abrogation of
      lymphoproliferative responses to ovalbumin. In addition, thymectomized calves
      treated with anti-CD4 mAb had significantly reduced immunoglobulin G1 and no
      detectable immunoglobulin G2 ovalbumin-specific antibody responses compared to
      thymus-intact anti-CD4 mAb-treated calves. The results of this study demonstrate
      that both thymectomy and treatment with anti-CD4 mAb are required for long-term
      in vivo depletion of functional bovine CD4+ T lymphocytes.

PMID- 11328377
TI  - CD8+ T cells in human uterine endometrial lymphoid aggregates: evidence for
      accumulation of cells by trafficking.
AB  - Lymphoid aggregates (LA) develop during the proliferative phase of the menstrual
      cycle in the human uterine endometrium (EM). They contain mostly CD8+ T cells and
      B cells. As these LA are absent immediately following menses, they may arise by
      division of cells resident in the EM, or by division of a limited number of
      precursor cells that traffic into the EM during the early proliferative phase of
      the menstrual cycle. Alternatively, they may arise by the continuous trafficking
      of cells into the EM throughout the proliferative phase of the menstrual cycle.
      In this study we investigated the distribution and frequency of CD8+ T cells in
      the aggregates using expression of Vbeta2 or Vbeta8 as markers of clonality and
      Ki-67 as a marker of dividing cells. Confocal microscopic analysis of endometrial
      tissues showed the random distribution of CD8+ T cells within aggregates within
      the same sample and in aggregates from different samples. Furthermore,
      comparisons of the distribution of Vbeta2 and Vb8 with expected values predicted
      from Poisson distribution values were not significantly different, suggesting
      that CD8+ T cells do not arise by division from single precursors. A low level of
      T-cell division within LAs was confirmed by positive staining for Ki-67. Dividing
      T cells were randomly dispersed throughout the LA and the frequency of dividing
      cells did not vary greatly between aggregates within the same tissue. Nearest
      neighbour analysis of dividing cells showed no statistically significant
      deviations from a random distribution. Taken together, these results suggest that
      LA develop during the menstrual cycle largely by the trafficking of cells to
      nucleation sites within the EM, rather than by division of a limited number of
      precursor cells.

PMID- 11328378
TI  - Analysis of recombinant mycobacteria as T helper type 1 vaccines in an allergy
      challenge model.
AB  - The potential for development of mycobacteria as T helper type 1 (Th1) vaccines
      capable of induction of Th1 responses to recombinant antigens was explored in a
      model system based on an immunodominant peptide from house dust mite. Different
      recombinant mycobacterial preparations were compared for their ability to induce
      a Th1 response to the peptidea. It was found that mycobacterial viability was not
      a prerequisite for Th1 immunogenicity. A dominant interferon-gamma (IFN-gamma)
      response to peptide was observed in splenocytes from C57BL/6J mice immunized with
      live or heat-killed preparations of recombinant Mycobacterium vaccae or with live
      attenuated bacillus Calmette-Guerin (BCG) vaccine expressing the antigen.
      Interleukin-5 (IL-5), a marker of a Th2 response, was detected only in mice
      receiving live M. vaccae. A similar pattern was observed in BALB/b mice, although
      the magnitude of the IFN-gamma response was much lower. Control and immunized
      mice were subsequently exposed to allergen using a Th2-inducing challenge
      protocol. A significant shift from a Th2 to a Th1 response was observed in
      immunized mice, as judged by cytokine expression by splenocytes and by subclass
      of circulating antibody. The effect was seen in three inbred mouse strains
      differing in their innate bias towards Th1 or Th2 responses. It was dependent on
      the presence of specific antigen in the mycobacterial preparation and, under the
      immunization conditions tested, was more pronounced with dead M. vaccae than with
      live BCG as carrier vaccine. The results demonstrate the potency of killed
      mycobacteria as Th1 adjuvants and suggest a potential application for recombinant
      mycobacteria in antigen-specific immune modulation.

PMID- 11328379
TI  - Intensive generation of NK1.1- extrathymic T cells in the liver by injection of
      bone marrow cells isolated from mice with a mutation of polymorphic major
      histocompatibility complex antigens.
AB  - Whether intermediate TCR (TCRint) cells and natural killer T (NKT or
      NK1.1+TCRint) cells are extrathymically generated remains controversial. This
      arises from the fact that there are few of these T cells in athymic nude mice and
      neonatally thymectomized mice. However, when athymic mice were provided with
      appropriate microenvironments or stimulation, many TCRint cells (mainly NK1.1-)
      were found to arise in the liver. NKT cells are known to be positively selected
      by monomorphic major histocompatibility complex (MHC) -like antigens (e.g. CD1d).
      This is true even if they are CD4+. In other words, a MHC class I-like antigen is
      restricted to CD4 antigen. This rule is somewhat different from that seen in
      conventional T cells (i.e. the restriction of class II with CD4 and that of class
      I and CD8). In the case of NK1.1-TCRint cells, they were selected by polymorphic
      MHC antigens, but their MHC restriction to CD4 or CD8 antigen was incomplete.
      This was revealed by experiments of bone marrow transfer with class I (bm 1) or
      II (bm 12) disparity. Depending on the disparity, a unique cytokine profile in
      sera was detected. These results suggest that the development of T lineage
      lymphocytes and MHC restriction to CD4 and CD8 might have occurred in parallell
      as a phylogenic event, and that NK1.1- extrathymic T cells (i.e. NK1.1-TCRint)
      are at an intermediate position between NKT cells and conventional T cells in
      phylogeny.

PMID- 11328380
TI  - Lipidation of T helper sequences from hepatitis C virus core significantly
      enhances T-cell activity in vitro.
AB  - Successful elimination of the hepatitis C virus (HCV) during acute infection has
      been linked to strong HCV-specific in vitro T-cell proliferation, whereas T cells
      from patients with chronic hepatitis C respond only weakly to HCV antigens. Lipid
      coupled peptides are immunostimulants, which might provide a basis for novel
      therapeutic strategies against HCV. Therefore, in 20 patients with chronic
      hepatitis C, we studied whether tri-palmitoyl-S-cysteine-coupled peptides could
      modify in vitro T-cell proliferation (by [3H]thymidine uptake) in response to
      virus core and NS4. The lipopeptides corresponded to five immunodominant T helper
      epitopes of HCV core. Contrary to unmodified peptides, the lipopeptides
      specifically enhanced [3H]thymidine uptake in response to HCV antigens but not to
      a non-HCV related control antigen. They increased the frequency of responders
      (stimulation index, SI > or = 4) to core (13/20 versus 2/20; p = 0.0008) and NS4
      (20/20 versus 7/20; p < 0.0001) among our patients with chronic hepatitis C. This
      immunostimulatory effect was dose-dependent, and was observed specifically with
      lipopeptides corresponding to the HCV epitopes. Our data demonstrate that the
      poor in vitro T-cell proliferation of patients with chronic hepatitis C can be
      improved when T cells are co-stimulated with HCV core-derived T helper
      lipopeptides, while the same peptides in unlipidated form had no effects. Thus,
      lipopeptides corresponding to HCV T-cell epitopes may offer novel
      immunomodulatory strategies against HCV.

PMID- 11328381
TI  - Immune responses in tuberculosis: antibodies and CD4-CD8 lymphocytes with
      vascular adhesion molecules and cytokines (chemokines) cause a rapid antigen
      specific cell infiltration at sites of bacillus Calmette-Guerin reinfection.
AB  - Rabbit primary dermal bacillus Calmette-Guerin (BCG) lesions were compared with
      reinfection BCG lesions in order to gain insight into how immune responses
      protect against clinical tuberculosis. As early as 3 hr, a marked infiltration of
      macrophages and lymphocytes occurred in the reinfection group, while very little
      cell infiltration occurred in the primary group. It seems that only an antigen
      antibody reaction could produce such an immediate pronounced antigen-specific
      chemotactic effect, because very few lymphocytes are normally present in the
      skin. Therefore, antibodies hasten the accumulation of an expanded antigen
      specific T-lymphocyte population (memory cells) at sites of bacillary lodgement.
      By 1-2 days, the primary and reinfection BCG lesions differed 400- to 500-fold in
      size. By 4-5 days, the size of the reinfection lesions had declined, while the
      size of the primary lesions had increased, so that, grossly, both types of lesion
      were similar. At 8 days in reinfection lesions and at 12 days in primary lesions,
      small secondary peaks in size occurred, which were probably caused by cell
      mediated immune responses. In rabbits with primary BCG lesions, skin tests with
      Old Tuberculin were positive at 9 days, accompanied by a rise in the levels of
      antibodies to the secreted antigen, phosphate-specific transport protein 1, but
      the levels of antibodies to the constitutive antigens, purified protein
      derivative and heat-shock protein 65, did not increase appreciably until some
      time after 23 days. In tissue sections of reinfection BCG lesions, the percentage
      of mononuclear cells labelled, by in situ hybridization techniques, for the mRNA
      of monocyte chemoattractant protein 1 (MCP-1), a chemokine, peaked at 3 hr and
      then was down-regulated, whereas in primary lesions, this percentage was down
      regulated only after 2 days. [The percentage in the tissue sections for the mRNAs
      of interleukins 1beta and 8, as well as the proteins of MCP-1 and tumor necrosis
      factor alpha (TNF-alpha), followed a somewhat similar time-course to that of MCP
      1 mRNA.] A high percentage of mononuclear cells containing the MCP-1 mRNA
      'factory' would favour enlargement of the lesions and a low percentage would
      favour their regression. At 5 days, the percentage of CD4 and CD8 lymphocytes,
      stained by immunohistochemical techniques, and the amount of microvasculature
      stained similarly for vascular cell adhesion molecule 1 were higher in the
      reinfection group, indicating that prior immunization caused a more rapid
      (antigen-dependent) up-regulation of these factors. Tuberculin reactions
      resembled early reinfection BCG lesions in almost every factor evaluated herein.
      In brief, the production of chemokines began soon after BCG reinfection, peaked
      within a few hours and was markedly down-regulated by 24 hr, a time at which the
      lesions of reinfection were of maximal size. Therefore, the amount of cell
      infiltration was tightly controlled, probably by the variety of mechanisms listed
      herein.

PMID- 11328382
TI  - Modulatory effect of prostaglandins on human monocyte activation for killing of
      high- and low-virulence strains of Paracoccidioides brasiliensis.
AB  - The effect of indomethacin (Indo), a cyclo-oxygenase inhibitor, on the monocyte
      mediated killing of a low- (Pb265) and a high- (Pb18) virulence strain of
      Paracoccidioides brasiliensis was examined. The Pb18 strain was not killed by
      either non-activated or interferon-gamma (IFN-gamma) -activated human monocytes
      but these cells did show fungicidal activity if pretreated with Indo. In contrast
      with IFN-gamma, tumour necrosis factor-alpha (TNF-alpha) was very effective at
      stimulating the fungicidal activity of monocytes. While the low-virulence strain,
      Pb265, could not be killed by monocytes, cells preincubated with IFN-gamma
      demonstrated fungicidal activity. The killing of this strain was also induced by
      pretreatment of monocytes with Indo. The results suggest a negative role for
      prostaglandins, which are synthesized via the cyclo-oxygenase pathway, in the
      regulation of monocyte-mediated killing of virulent and avirulent strains of P.
      brasiliensis and that TNF-alpha generation during the fungus-monocyte interaction
      is more important in the killing of Pb265 than Pb18.

PMID- 11328383
TI  - Tumours can act as adjuvants for humoral immunity.
AB  - Tumour cells transfected with cDNAs encoding non-self proteins were used to
      investigate the ability of the immune system to respond to immunogenic antigens
      expressed by tumours. Secreted, intracellular and surface proteins were used as
      model antigens, as these reflect the potential forms of tumour antigens.
      Syngeneic BALB/c mice injected with viable line 1 lung carcinoma or EMT6 mammary
      tumour cells secreting ovalbumin (OVA) or prostate-specific antigen (PSA)
      produced very high immunoglobulin G (IgG) antibody titres, equivalent to those of
      mice injected with protein in Freund's complete adjuvant (FCA). Secretion of the
      antigens was not necessary as tumour cells expressing a cell-surface antigen (HER
      2/Neu) or an intracellular antigen - green fluorescence protein (GFP) - also
      generated high-titre antigen-specific IgG antibodies. In interleukin-4 (IL-4)
      deficient mice, both IgG1 and IgG2a were produced in response to OVA administered
      in FCA, whereas in response to tumour-produced antigen, the antibodies switched
      from predominantly IgG1 to IgG2a, indicating that the mechanisms responsible for
      antibody induction differed between these forms of immunization. In contrast to
      the line 1 and EMT6 tumours, which are of BALB/c origin, OVA- or PSA-producing
      B16 melanoma cells, which are of C57BL/6 origin, failed to elicit antibody
      production. This was not the result of strain differences, as a similar finding
      was observed when the tumours were grown in (BALB/c x C57BL/6)F1 mice, but
      appeared to be caused by intrinsic differences in the tumours. Furthermore, co
      injection of both B16/OVA and line 1 tumours resulted in production of anti-OVA
      antibody, indicating that B16 tumours were not immunosuppressive, but instead
      line 1 tumours appear to exert an adjuvant effect.

PMID- 11328384
TI  - The 3'-untranslated region of human interleukin-8 mRNA suppresses IL-8 gene
      expression.
AB  - Although adenosine/uridine (AU)-rich sequences in the 3'-untranslated region
      (UTR) of the interleukin-8 (IL-8) gene have been suggested to contribute to its
      post-transcriptional regulation, the molecular basis whereby this occurs still
      needs to be understood. To investigate the role of the 3'-UTR on human IL-8 gene
      regulation, chimeric reporter genes were generated by adding full length or
      differentially deleted 3'-UTR of the IL-8 gene to chloramphenicol
      acetyltransferase (CAT). Addition of the entire IL-8 3'-UTR markedly reduced CAT
      mRNA and protein expression in COS 7 cells. In a reporter gene study, IL-8 3'-UTR
      destabilized CAT mRNA, which was dependent on active transcription in COS 7
      cells. A 357-base sequence (nucleotides (nt) 2387-2743 of genomic DNA) within 3'
      UTR, designated e, suppressed CAT gene expression by accelerating CAT mRNA
      turnover. A 26-base AU-rich sequence (nt 2552-2577) within e, containing four
      AUUUA pentamers that form two UAUUUAUU and one UUAUUUAU octamers, did not
      suppress CAT gene expression. However, deletion of the AU-rich sequences
      attenuated the inhibitory effect of e on CAT gene expression. Elimination of the
      first 100 bases (nt 2386-2486) attenuated the potency of fragment e, but much
      weaker than elimination of the first 146 bases (nt 2387-2533). This study gives
      new insights in unravelling the molecular mechanisms involved in the post
      transcriptional regulation of the IL-8 gene.

PMID- 11328385
TI  - The role of hepatocyte growth factor and its receptor c-met in interactions
      between lymphocytes and stromal cells in secondary human lymphoid organs.
AB  - Secondary lymphoid tissue consists of two major populations of cells: lymphoid
      cells and stromal cells. It is generally accepted that these two cell populations
      influence each other however, factors mediating these processes are poorly
      understood. In this paper we characterize one of the possible means of
      communication between stroma and lymphocytes namely through hepatocyte growth
      factor/c-met receptor interactions. Hepatocyte growth factor (HGF) is a
      pleiotropic factor that is mainly produced by mesenchymal cells and acts on cells
      of epithelial origin which express the HGF receptor c-met. Here we demonstrate
      that biologically active HGF is constitutively produced by fibroblast-like
      stromal cells from human lymphoid tissues. HGF secretion from stromal cells was
      increased by direct contact with activated T cells. This increase was abrogated
      when activated T cells were separated physically from stromal cells. Using
      neutralizing antibody or cytokine inhibitors we provide evidence that enhancement
      of HGF production was due to additive effects of T-cell membrane-associated
      interleukin-1 (IL-1) and CD40 ligand. Finally, we also show that B lymphocytes
      activated with CD40L/anti-mu or phorbol 12-myristate 13-acetate (PMA) express c
      met receptor. Co-culture of activated B cells with stromal cells from spleen
      leads to enhanced production of immunoglobulins. This can be partially inhibited
      by introduction of anti-HGF neutralizing antibodies to the culture system.
      Substitution of stromal cells with recombinant HGF did not produce enhancement of
      immunoglobulin secretion. On the other hand stimulation of c-met receptor with
      HGF leads to enhanced integrin-mediated adhesion of activated B cells to vascular
      cell adhesion molecule (VCAM-1) and fibronectin. On the basis of the above
      experiments we conclude that HGF production by fibroblast-like stromal cells can
      be modulated by activated T cells, thus providing signals for the regulation of
      adhesion of c-met expressing B cells to extracellular matrix proteins. In this
      way HGF may indirectly influence immunoglobulin secretion by B cells.

PMID- 11328388
TI  - Cutaneous and noncutaneous disorders treated with extracorporeal photopheresis.

PMID- 11328387
TI  - Pharmacologic alternatives for severe atopic dermatitis.

PMID- 11328389
TI  - Digital fluorescence as a parameter of Propionibacterium acnes suppression needs
      assessment.

PMID- 11328390
TI  - Suspected skin malignancy: a comparison of diagnoses of family practitioners and
      dermatologists in 493 patients.
AB  - BACKGROUND: In the Irish health system, dermatology patients present to their
      family practitioner for diagnosis and treatment, and are referred to a
      dermatologist for a second opinion where diagnosis is in doubt or when there has
      been therapeutic failure. The level of expertise in dermatology amongst family
      practitioners varies considerably. AIM: To compare the diagnoses of general
      practitioners and dermatologists over a selected period in patients with a
      possible diagnosis of skin cancer. METHODS: Four hundred and ninety-three
      patients were seen by one of two dermatologists over a 1-year period at a rapid
      referral clinic for patients suspected by their family practitioners of having
      unstable or possibly malignant skin lesions; 213 of these patients had a
      diagnosis made on clinical examination by the dermatologist, while 264 had
      diagnostic or therapeutic biopsies performed; 16 patients defaulted on surgery.
      RESULTS: The diagnoses of the family practitioners agreed with the diagnoses of
      the dermatologists on patients diagnosed clinically in 54% of cases. Thirty-eight
      patients had histologically proven skin malignancy. These were diagnosed
      accurately by the referring family practitioner in 22% of patients, while the
      dermatologists made the correct diagnosis prior to biopsy in 87%. CONCLUSIONS: In
      over 50% of cases diagnosed clinically, the dermatologist and family practitioner
      agreed. Histologically proven skin cancers were diagnosed accurately in only 22%
      of cases by family practitioners, compared to 87% of cases by dermatologists.
      Specific areas of diagnostic difficulty for family practitioners include benign
      pigmented actinic and seborrheic keratoses, squamous cell carcinoma, and
      melanoma. Postgraduate education for family practitioners should be directed
      towards these areas of deficiency. Dermatologists had difficulty distinguishing
      pigmented actinic keratoses from melanoma.

PMID- 11328391
TI  - Risk factors for cutaneous melanoma: a case-control study in Argentina.
AB  - BACKGROUND: Although cutaneous malignant melanoma (CMM) is still a relatively
      rare neoplasm, incidence rates are increasing in many white populations
      worldwide. A case-control study was performed in Argentina to estimate the risk
      factors for CMM. METHODS: The study group comprised 101 hospital cases with
      histologically verified melanoma and 246 controls, frequency matched by age, sex,
      and hospital. Individuals were interviewed about demographic and constitutional
      factors and sun exposure history. RESULTS: The following risk factors were
      significant in the logistic analysis: nevi on arms (odds ratio (OR) = 6.3 for 20
      or more), skin phototype (OR = 4.1 for type l or ll), holidays spent at the beach
      (OR = 4 for more than 6 weeks lifelong), fair skin tone (OR = 3.4), light eye
      color (OR = 2.8), sunburn before the age of 15 years (OR = 2.4), and
      participation in outdoor sports (OR = 3.2 for more than 5790 h accumulated in a
      lifetime). Occupational sun exposure was not related to CMM risk. Educational
      level, hair color, and the presence of freckles were not independent risk factors
      for CMM. CONCLUSIONS: The risk factors found for the studied population, with
      nearly 90% of the individuals born in Argentina and with nearly 50% with four
      southern European grandparents, were consistent with those described for other
      countries. This investigation has resulted in findings that may be of use in
      preparing actions to prevent CMM in Argentina; these should be directed at those
      individuals who present the above mentioned risk factors. These actions should
      include instructions to avoid excessive sun exposure, with the aim to reduce
      melanoma incidence.

PMID- 11328392
TI  - Pemphigus in South Africa.
AB  - BACKGROUND: Pemphigus is an autoimmune disease characterized by intraepidermal
      blistering. We describe the demography, prevalence, clinical features, response
      to treatment, and human leukocyte antigen (HLA) characteristics of pemphigus in
      Kwa-Zulu Natal, South Africa. METHODS: All patients with pemphigus were
      prospectively recruited over 12 years from January 1987 to December 1999. The
      demography, clinical features, histology, and immunofluorescence (IF) were
      recorded. In a subset of patients, HLA tests were performed. RESULTS: One hundred
      and twelve patients had pemphigus. Pemphigus foliaceus (PF) was the commonest
      variant seen (62 patients) and 80% of these patients were black. The mean age was
      43 years (12-93 years) and the male to female ratio was 1 : 1.4. Fifty patients
      had pemphigus vulgaris (PV), of whom 82% were Indian. The mean age of
      presentation of PV was 48 years (21-82 years). The male to female ratio was 1 :
      1.7. There was no mucosal involvement in PF. PV patients had painful oral
      lesions. The mortality rate was 14% in the total sample (six in PV and two in
      PF). HLA-B8 was positive in 41% of patients with PF (P < 0.001). CONCLUSIONS: PF
      occurs more commonly in black people, while most cases in Indians present with
      the PV subtype. Pemphigus patients present with severe and extensive disease, and
      PV patients share features in common with patients from their land of origin
      (India), suggesting a genetic link.

PMID- 11328393
TI  - Dermatomyositis and mucinosis.
AB  - BACKGROUND: Mucin deposition is a common feature in autoimmune collagen diseases
      including dermatomyositis. Nevertheless, clinical manifestations of mucinosis are
      uncommon in patients with dermatomyositis. Two cases of mucinosis associated with
      dermatomyositis are reported. PATIENTS: A 53-year-old woman presented with
      symmetrical plaques on the upper limbs formed by the coalescence of small,
      violaceous papules. In addition, she showed the typical cutaneous and muscle
      features of dermatomyositis. A 44-year-old woman with dermatomyositis of 5 years'
      evolution developed linear, flesh-colored papules across the flexural creases of
      her palms and fingers. RESULTS: Skin biopsy of the upper limb lesions in the
      first patient showed epidermal changes compatible with dermatomyositis and dermal
      mucin deposition. Histopathologic examination of the palmar lesions of the second
      patient showed less intense epidermal changes of dermatomyositis and dermal mucin
      deposition. CONCLUSIONS: Mucin deposition in patients with dermatomyositis may
      have an unusual clinical presentation, and it should be considered in the
      differential diagnosis of atypical cutaneous lesions in these patients.

PMID- 11328394
TI  - Multiple eccrine hidrocystomas of the face.
AB  - BACKGROUND: Multiple eccrine hidrocystomas of the face are a rare facial
      dermatosis for which no recent large series of cases has been reported.
      OBJECTIVE: To describe the clinicopathologic features of five cases of multiple
      eccrine hidrocystoma and to emphasize their similar characteristics. METHODS: The
      clinical and histologic features of five women with multiple eccrine
      hidrocystomas of the face are described. RESULTS: All cases were middle-aged
      women with numerous, asymptomatic, skin-colored to bluish, papulonodular skin
      lesions, ranging from 2 to 5 mm in diameter, and mainly centrifacial in
      distribution. Histopathologically, all cases showed unilocular cysts in the
      dermis lined by two layers of cuboidal cells. Staining for S-100 protein was
      negative in the cyst wall in all cases. One case was treated with topical 1%
      atropine for 3 weeks with no significant improvement. No systemic side-effects
      were observed during this treatment. CONCLUSIONS: Multiple eccrine hidrocystomas
      are a rare condition which might be confused clinically and histopathologically
      with apocrine hidrocystomas. To date, no effective treatment has been reported.

PMID- 11328395
TI  - Hereditary palmoplantar keratoderma (four cases in three generations).
AB  - A 39-year-old man reported with progressive thickening of the skin of the hands
      and feet and an inability to flex his hand. It was largely asymptomatic; however,
      brisk walking caused excessive sweating, pain, and widening of the fissures on
      the soles of the feet. He was unable to walk barefooted. According to his mother,
      the first episode presented with blistering at 7 days of age. Ever since, the
      condition has steadily worsened to acquire the current status. He was married at
      the age of 18 years, and had a stillborn child 18 months afterwards. Presently,
      he has three children, two girls aged 14 and 12 years and a son aged 10 years.
      Both the daughters are similarly affected. While cataloguing the details of the
      pattern of inheritance, the mother of the index case was also found to be
      affected (Fig. 1). The natural history of the disease was identical. Examination
      of the palms was marked by pronounced thickening of the skin resulting in the
      masking of palmar creases. The thickening was well demarcated and its margins
      were prominent and surrounded by an erythematous halo. The color of the skin was
      yellow and waxy (Fig. 2a). Contractures were present on all the fingers;
      nevertheless, the deformity of the middle and distal interphalangeal joints of
      the little finger was prominent. The soles of the feet had a similar morphology.
      In addition, marked fissuring was obvious (Fig. 2b). His daughters had an
      identical affliction of the palms and soles. The texture and morphology of the
      nails were normal. Light microscopy performed on scrapings from the fissures,
      mounted on 10% potassium hydroxide, revealed mycelia (hyphae) and spores.
      Hematoxylin and eosin-stained microsections from the palms and soles showed
      exquisite changes in the epidermis characterized by considerable uniform
      orthohyperkeratosis. Hypergranulosis and acanthosis were other associated
      changes. In addition, perinuclear vacuolization and keratohyalin granules of
      varying sizes and shapes were located at the periphery of the cells. A sparse
      mononuclear infiltrate was located at the dermo-epidermal junction. Hyphae and
      spores of fungi were also identified in the stratum corneum (Fig. 3).
      Itraconazole, 400 mg/day in two equally divided doses, was administered with
      major meals for 7 days. In addition, high doses of vitamin A (100,000 IU) were
      given daily for 2 weeks, supplemented by 12% salicylic acid (Salicylix SF12)
      ointment for daytime application and an ointment containing 6% coal tar and 3%
      salicylic acid (Salytar) for night-time application. This treatment is useful in
      recalcitrant cases.

PMID- 11328396
TI  - Eruptive lesions in a patient with bone marrow transplantation.

PMID- 11328397
TI  - Pyoderma gangrenosum associated with c-ANCA (h-lamp-2).

PMID- 11328398
TI  - Drugs and Wells' syndrome: a possible causal relationship?

PMID- 11328399
TI  - Cutaneous T-cell lymphoma presenting as disseminated, pigmented, purpura-like
      eruption.

PMID- 11328400
TI  - Neutrophilic eccrine hidradenitis unassociated with chemotherapy in a patient
      with acute myelogenous leukemia.

PMID- 11328401
TI  - Wells' syndrome: report of a case and review of the literature.

PMID- 11328402
TI  - Livedoid vasculitis responding to PUVA therapy.
AB  - BACKGROUND: Livedoid vasculitis is a chronic disorder manifested as recurrent,
      painful, reticulated, and ulcerative lesions of the legs, which result in ivory
      atrophic scars with peripheral telangiectasia and hyperpigmentation. Its etiology
      remains obscure and therapy is difficult. In this study, we evaluated the
      clinical efficacy of psoralen plus UVA (PUVA) therapy and its side-effects in the
      treatment of livedoid vasculitis. METHODS: Eight South Korean patients with
      livedoid vasculitis were treated with UVA and 8-methoxypsoralen (8-MOP). Systemic
      PUVA was started with 4 J/cm2 of UVA two or three times a week, and then the dose
      was increased by 0.5 or 1 J/cm2 increments at each subsequent treatment as
      tolerated. The effects of treatment were evaluated using photographs of before,
      during, and after the study. RESULTS: All patients experienced rapid cessation of
      new lesion formation, significant symptom relief, and complete healing of primary
      lesions. The mean times for each of the above were 3.6, 5.9, and 10 weeks, and
      the mean cumulative doses of UVA for each of the above were 55.9, 96.8, and 197.9
      J/cm2, respectively. The patients tolerated PUVA therapy well without
      unacceptable side-effects. CONCLUSIONS: We propose that systemic PUVA using 8-MOP
      should be investigated further as an alternative treatment for patients with
      livedoid vasculitis.

PMID- 11328403
TI  - Cost-effectiveness of Dead-Sea climatotherapy and balneophototherapy of
      psoriasis.

PMID- 11328404
TI  - Cutaneous leishmaniasis in Pakistan.

PMID- 11328406
TI  - Is concurrent chemotherapy and radiotherapy the new standard of care for locally
      advanced cervical cancer?
AB  - The results of five multi-institutional randomized controlled trials
      demonstrating a survival advantage for the concurrent administration of
      chemotherapy and radiotherapy in the management of cervix cancer represented the
      first major advance in the management of this malignancy in many years and
      prompted many practitioners to alter their pattern of practice. More recently,
      the results of the National Cancer Institute of Canada (NCIC) trial demonstrating
      no survival benefit when combined modality therapy is compared with optimally
      delivered radiotherapy, has led many to question the strength of the evidence
      supporting the adoption of combined modality therapy as the standard therapy for
      cervix cancer and in particular the magnitude of the benefit derived from the
      addition of chemotherapy to an optimally delivered radiotherapy regimen. This
      review paper will critically examine the evidence presented in the literature
      indicating a benefit for the use of combined modality therapy, discuss possible
      reasons why the conclusions of negative trials such as the NCIC study differ from
      those of the other studies and highlight those aspects of the use of combined
      modality therapy that require further evaluation.

PMID- 11328407
TI  - Telomerase-A molecular marker for cervical cancer screening.
AB  - Cervical cancer is one of the most common cancers in women and can be routinely
      screened for by the Papanicolaou smear. Screening for HPV high-risk types 16 and
      18 has augmented the sensitivity of this test, but still some cases remain
      undetected. We have investigated the utility of assaying telomerase activity as a
      possible screening marker for cervical cancer. Telomerase activity was studied in
      relation to HPV 16/18 infection, Papanicolaou smear cytopathology, and biopsy
      histopathology in a total of 88 subjects, consisting of 29 cervical cancer cases,
      19 control hysterectomy samples, 16 precancerous cervical scrapes, 6 cervical
      samples from other gynecological malignancies, and 18 normal healthy cervical
      scrapings. Telomerase activity was detected in 96.5% of cervical tumor samples
      and in 68.7% of premalignant cervical scrapings but was not detected in control
      hysterectomy samples and in cervical scrapings of normal healthy controls.
      Telomerase assay had a diagnostic accuracy of 95.8 in tissue samples, 79.1 in
      scrapings and 91.2 in all. Whereas HPV-16/18 subtyping had a diagnostic accuracy
      of 89.5% in tissue samples, 70.5% in scrapings, and 82.1% in all. There was also
      71% agreement between telomerase activity and HPV-16/18 infection. The absence of
      telomerase activity in cervical scrapes from healthy women indicated the
      potential of telomerase to serve as a good screening marker for the early
      diagnosis of cervical cancer. For the first time we have also shown the ability
      of telomerase to detect micro and probably occult metastasis in gynecological
      malignancies.

PMID- 11328408
TI  - Glutathione S-transferase GSTM1 and GSTT1 genotypes in ovarian cancer:
      association with p53 expression and survival.
AB  - The objective of this study was to determine whether the association between
      GSTM1 null/GSTTI null and survival in ovarian cancer is mediated by the influence
      of these genes on p53 expression. In 81 women with pure invasive ovarian cancer,
      GSTM1 null and GSTT1 null genotypes were identified using polymerase chain
      reaction and p53 expression was assessed using immunohistochemistry. The
      association of these factors with survival was examined using Cox's proportional
      hazards regression models. Performance status (P < 0.001), operative stage (P =
      0.004), residual disease (P = 0.001), histologic subtype (P = 0.05), tumor grade
      (P = 0.007), and the combined GSTMI null/GSTTl null genotype (P = 0.023) were all
      individually associated with survival. p53 expression was not associated with
      survival (P = 0.45). In a multivariate analysis, the effects of GSTM1 null/GSTT1
      null on survival were lost when residual disease and tumor grade were included.
      The effects of p53 expression on survival were unchanged when residual disease,
      tumor grade, operative stage, and performance score were included. GSTM1
      null/GSTT1null did not influence the effects of p53 expression on survival and
      vice versa. The GSTM1 null/GSTT1 null genotype was associated with response to
      primary chemotherapy (P = 0.007) but p53 expression was not. We conclude that the
      association of GSTM1 null/GSTTl null with survival appears to be mediated through
      different mechanisms to p53 expression in ovarian cancer and in addition, may be
      a better predictor of outcome.

PMID- 11328409
TI  - Cell cycle proteins as molecular markers of malignant change in vulvar lichen
      sclerosus.
AB  - Lichen sclerosus (LS) has a known association with the development of squamous
      cell carcinoma of the vulva. The purpose of this study was to investigate
      molecular markers, which could indicate premalignant changes. Multiple sequential
      vulvar biopsies were taken over a period of 11 years from a patient with
      longstanding LS. Immunohistochemical staining was used to demonstrate a range of
      molecular markers. Increased expression of p53 and Ki67 was found in areas of
      squamous hyperplasia (SH) and differentiated vulvar intraepithelial neoplasia
      (dVIN) which correlated with the subsequent development of invasive squamous cell
      carcinoma (SCC). Molecular changes have been found to accompany histologic
      changes in the progression of vulvar LS to malignancy. Such markers may prove a
      useful addition in the clinical management of these conditions.

PMID- 11328410
TI  - The growth factor receptors HER-2/neu and EGFR, their relationship, and their
      effects on the prognosis in early stage (FIGO I-II) epithelial ovarian carcinoma.
AB  - Epithelial ovarian cancer is a heterogeneous disease and many biologic and
      molecular factors are important for its development and progression, including
      growth rate, metastatic potential, chemo- and radiosensitivity, and prognosis.
      Even in the early stages (FIGO I-II), many questions persist about the biologic
      behavior, optimal treatment, and prognosis. In a series of 106 patients with
      epithelial ovarian cancers in FIGO stages IA-IIC, a number of known prognostic
      factors (age, FIGO stage, histopathologic type, and tumor grade) were studied in
      relation to two important growth factor receptors for oncogenesis (HER-2/neu and
      EGFR). Immunohistochemical techniques were used. All patients received adjuvant
      radiotherapy 4-6 weeks after the primary surgery. In a univariate analysis, the
      expression of the HER-2/neu receptor was not associated with any of the
      clinicopathologic factors studied or survival status. Positive EGFR staining was
      associated with poor survival in a univariate analysis. Co-expression of HER
      2/neu and EGFR was most frequently seen in serous tumors and positive staining
      for HER-2/neu alone was associated with mucinous tumors. Both endometrioid and
      clear cell tumors belonged to the largest subgroup with concomitant negativity
      for both HER-2/neu and EGFR. In a multivariate Cox analysis, the tumor grade and
      EGFR status of the tumors were independent and significant prognostic factors. A
      therapeutic strategy for epithelial ovarian cancer might be to decrease EGFR
      expression by gene therapy in combination with adjuvant radiotherapy or
      chemotherapy.

PMID- 11328411
TI  - Preoperative assessment of deep myometrial and cervical invasion in endometrial
      carcinoma: comparison of magnetic resonance imaging and gross visual inspection.
AB  - This study aimed to evaluate the accuracy of magnetic resonance imaging (MRI) in
      the detection of deep myometrial invasion and cervical extension by endometrial
      carcinoma. We also aimed to compare MRI results to surgical staging of
      endometrial carcinoma. Forty women with a histologic diagnosis of endometrial
      carcinoma underwent a preoperative pelvic MRI. In 33 cases intraoperative gross
      visual inspection (GVI) of the surgical specimen was also evaluated. The results
      obtained were compared with the histologic diagnosis. Pathologic evaluation of
      the myometrium determined that superficial invasion was present in 25 patients
      and deep invasion in 15. The uterine cervix was found to be involved in 12 cases.
      The accuracy, sensitivity, and specificity of MRI and GVI were 93%/91%, 80%/77%,
      and 100%/100%, respectively, in detecting deep myometrial invasion and 80%/79%,
      33%/36% and 100%/100%, respectively, in determining cervical invasion. When the
      Kappa statistical measurement was applied, the results from each technique, MRI
      and GVI, showed an agreement on the evaluation of myometrial and cervical
      invasion by endometrial carcinoma. In conclusion, MRI, in this series, was
      demonstrated to be a reliable method for preoperative endometrial carcinoma
      "imagiological staging". The high accuracy achieved by MRI and GVI suggests that
      they may be used interchangeably.

PMID- 11328412
TI  - Hypoxia-stimulated expression of angiogenic growth factors in cervical cancer
      cells and cervical cancer-derived fibroblasts.
AB  - It is generally accepted that local growth of solid tumors and their ability to
      establish distant metastases are dependent on the formation of new blood vessels
      arising from preexisting ones (angiogenesis). The angiogenic response of the host
      is mediated by angiogenic molecules that are released from cancer and normal
      stroma cells, especially fibroblasts. The goal of the present study was to
      quantitatively compare the expression of the two most important angiogenic growth
      factors (VEGF, angiogenin) of cervical cancer cells (HeLa and Me-180) with that
      of cervical cancer-derived fibroblasts (from one tumor/patient) under defined
      normoxic and hypoxic conditions in vitro. The growth kinetics of cervical cancer
      cells (HeLa and Me-180) and tumor-derived fibroblasts were evaluated in vitro
      under normoxic and hypoxic conditions. Growth factor concentrations in the cell
      culture medium were measured by ELISA and the secretion rates per cell were
      calculated. Under normoxic conditions, both the cervical cancer cells as well as
      the tumor-derived fibroblasts released VEGF and angiogenin. The secretion rate of
      both angiogenic factors was significantly higher in the stroma cells than in the
      tumor cells (P < 0.05). VEGF and angiogenin secretion is significantly higher in
      the stroma cells under hypoxia than in the tumor cells investigated (P < 0.05).
      The presented data support the concept that in cervical cancer non-neoplastic
      fibroblasts could play a pivotal role in the complex process of tumor
      angiogenesis.

PMID- 11328413
TI  - Closed suction drainage versus no drainage following pelvic lymphadenectomy for
      gynecological malignancies.
AB  - The present study was undertaken in the Department of Gynecologic Oncology,
      Kidwai Memorial Institute of Oncology, Bangalore between October 1998 and July
      1999. One hundred and forty three consecutive patients with various gynecological
      malignancies undergoing pelvic +/- aorto-caval lymphadenectomy as part of
      definitive surgical procedures, were analyzed. Sixty nine patients had closed
      suction retroperitoneal pelvic drainage (Group A) and 74 patients had no suction
      drainage and no pelvic reperitonealization (Group B). The mean postoperative
      hospitalization was 10 days in both groups. Six patients in Group A and four
      patients in Group B developed paralytic ileus which responded to conservative
      line of management. Five patients in Group A and two patients in Group B
      developed lymphocysts (P > 0.05). The present study demonstrates that closed
      suction retroperitoneal pelvic drainage following pelvic + aorto-caval
      lymphadenectomy confers no advantage over no drainage & no pelvic
      reperitonealization. The partial closure of pelvic peritoneum with no drainage
      was associated with increased lymphocyst formation (7/25 cases, 28%) during the
      period immediately before this modified study was undertaken.

PMID- 11328414
TI  - P53, bcl-2, and bax: their relationship and effect on prognosis in early stage
      epithelial ovarian carcinoma.
AB  - The prognosis of ovarian carcinoma, even in the early stages (FIGO I-II),
      continues to present a challenge despite advances in the understanding of
      pathophysiology and treatment. In a series of 106 patients with epithelial
      carcinomas in FIGO stages IA-IIC, a number of prognostic factors (age, FIGO
      stage, histopathologic type, and tumor grade) were studied in relation to
      important regulators of apoptosis (p53, bcl-2, and bax). Immunohistochemical
      techniques were used. All the patients received adjuvant radiotherapy after the
      primary surgery. Univariate analysis showed that expression of p53 was highly
      significantly associated with tumor grade (P = 0.007) and survival status (P =
      0.046). Positive bcl-2 staining was associated with serous (P = 0.0002) and
      endometrioid tumor subtypes, but not with the survival rate. A positive bax
      status was associated with younger age (P = 0.012) and a more favorable
      probability of survival. A significant association between the bcl-2 and bax
      status of the tumors and histopathologic subtypes and grades was noted. The most
      favorable subgroup of tumors was that with a combination of positive bax staining
      and negative p53 staining. In a multivariate Cox analysis, tumor grade (P =
      0.0006) and bax status (P = 0.020) were independent and significant prognostic
      factors.

PMID- 11328415
TI  - Occult tumor cells in surgical specimens from cases of early cervical cancer
      treated by liposuction-assisted nerve-sparing radical hysterectomy.
AB  - Tumor recurrence in patients with cervical cancer after primary radical surgery
      with complete tumor resection (R0) may be caused by occult tumor cell deposits
      (OTCD) in potentially tumor-bearing pelvic tissue. New surgical techniques, like
      liposuction-assisted nerve-sparing radical abdominal hysterectomy (LANS-RH) might
      be performed to remove this tissue. In a preliminary study of 30 cases, treated
      with LANS-RH, the liposuction specimens were examined on hematoxylin & eosin
      (H&E)-stained step sections and at immunohistochemical levels, using the antibody
      cocktails MNF 116 and AE1/AE3 for cytokeratins to detect occult tumor cells. In
      nine cases microscopically tumor-free lymph nodes were detected in the
      liposuction material. One case presented lymphovascular space involvement in the
      capsular region of a node on H&E stained slides. Two additional cases showed
      tumor cell deposits in pelvic perinodal fatty tissue on immunohistochemical
      examination. We conclude that the LANS-RH technique is capable of resecting
      potentially tumor-bearing pelvic tissue. Careful histologic handling and
      immunohistochemical techniques may improve the detection of OTCD.

PMID- 11328416
TI  - Investigation of women with endometrial carcinoma using serum vascular
      endothelial growth factor (VEGF) measurement.
AB  - This study assessed whether serum VEGF measurement in women presenting with
      endometrial cancer could predict advanced stage disease. Preoperative sera from
      37 women undergoing laparotomy for suspected endometrial cancer were assayed for
      VEGF, CA125 and platelet count. Significant positive correlation was shown
      between VEGF and platelet levels (P = 0.003, r = 0.477). However, no correlation
      was demonstrated between VEGF and stage overall, and no significant difference
      was shown between those with early (stage 1A/1B, n = 20) compared to those with
      advanced (stage >1B, n = 13) or disseminated (stage >2, n = 7) disease. Serum
      VEGF measurement was not beneficial in the preoperative assessment of stage in
      patients with endometrial carcinoma. Strong correlation with platelet levels
      suggests that this is one of the sources of VEGF measured.

PMID- 11328417
TI  - Remission of metastatic cervical adenocarcinoma with weekly paclitaxel.
AB  - We report the use of paclitaxel in the successful treatment of a patient with
      recurrent adenocarcinoma of the cervix. Paclitaxel, 70 mg/m2 by 1-h infusion
      weekly, was administered to a 59-year-old patient with cervical adenocarcinoma
      showing lung metastasis. She showed partial clinical response after seven cycles,
      and at the completion of 20 cycles she showed complete response, which was
      confirmed by chest X-ray and computed tomography scan. Toxicities including
      neurotoxicity were mild. She showed an objective response to treatment for over 8
      months, and she enjoyed a favorable quality of life during and after treatment.
      Weekly paclitaxel was very well tolerated, yet was effective for recurrent
      cervical adenocarcinoma.

PMID- 11328418
TI  - Paraneoplastic cerebellar degeneration heralding fallopian tube adenocarcinoma.
AB  - The objective of this paper is to describe an 81-year-old woman with subacute
      cerebellar degeneration due to fallopian tube adenocarcinoma. Serum anti-Yo
      antibodies were used to screen for pelvic malignancy. Their presence led to a
      meticulous search, which included bilateral salpingoophorectomy. Subsequently an
      occult fallopian tube adenocarcinoma was discovered. This case report highlights
      the diagnostic value of antineuroneal antibodies in females with subacute
      neurologic impairment in the form of paraneoplastic syndrome.

PMID- 11328419
TI  - Pre-emptive renal transplantation in children.
AB  - BACKGROUND: Renal transplantation is a definitive therapeutic modality in end
      stage renal disease (ESRD). Most ESRD patients in Japan experience dialysis prior
      to renal transplantation. The present study was undertaken to examine the
      usefulness of pre-emptive renal transplantation (PET). METHODS: Between 1987 and
      1998, 255 renal transplantations were carried out by the authors. Among those
      consecutive cases, 10 were cases of PET. In nine pediatric cases, demographics,
      graft and patient survival, height growth and benefits from successful
      transplantation were studied and compared with age-matched dialyzed
      transplantation controls. RESULTS: All transplantation was living-related. There
      was a disparity of causes of ESRD between the two groups. In PET, acquired renal
      deterioration due to a congenital lower urinary tract disorder was the major
      cause. Graft and patient prognosis was favorable in both groups. Growth
      retardation in PET patients under 15 years of age was significantly less apparent
      at the time of transplantation and after 3 years compared to the control. The
      benefits from transplantation were different in the two groups. Most PET patients
      felt an improvement of their physical condition; however, all of the control
      patients felt that the major boon was the freedom from the restriction of the
      daily diet and time for dialysis. CONCLUSION: In pediatric renal transplantation,
      short-term preceding dialysis does not have a detrimental effect, but PET could
      benefit ESRD patients by maintaining their quality of life. Moreover, PET
      minimizes the production of renal dwarfism in prepubertal children. Thus, PET
      should be taken into consideration in the choice of renal replacement therapy.

PMID- 11328420
TI  - Prophylactic intravesical instillation of mitomycin C and cytosine arabinoside
      for prevention of recurrent bladder tumors following surgery for upper urinary
      tract tumors: a prospective randomized study.
AB  - BACKGROUND: A recurrence of bladder tumors following surgery for transitional
      cell carcinoma of the upper urinary tract is not rarely observed. A prospective
      randomized study was conducted to examine the significance of prophylactic
      intravesical instillation of mitomycin C (MMC) and cytosine arabinoside (Ara-C)
      to prevent recurrent bladder tumors after surgery for superficial transitional
      cell carcinoma of the upper urinary tract. METHODS: The patients were randomized
      into an instillation group, who received postoperative intravesical instillation
      of MMC (20 mg) and Ara-C (200 mg) 28 times over a period of 2 years, and a non
      instillation group. The non-recurrence rate was then compared between the groups.
      RESULTS: Of the 27 patients registered, 25 patients (13 with instillation and 12
      without instillation) were able to be evaluated, with a median follow-up period
      of 45 months. The non-recurrence rate of bladder tumors in the instillation group
      was higher than that in the non-instillation group. Although the difference was
      not statistically significant, the P-value (P = 0.079) demonstrated a strong
      trend. When any possible bias was allowed for a multivariate analysis, the
      difference was almost significant (P = 0.0567). No patients withdrew from this
      study due to any side-effects. CONCLUSION: The postoperative instillation of MMC
      and Ara-C may be a useful approach for reducing the recurrence of bladder tumors
      after surgery for upper urinary tract tumors.

PMID- 11328421
TI  - A clinical study of urine basic fetoprotein and urine polyamine as tumor markers
      in epithelial cancer of the urinary tract.
AB  - BACKGROUND: The reliability of a new screening test for epithelial cancer of the
      urinary tract was evaluated and the results were compared with those obtained
      employing urinary cytology in routine use. METHODS: The subjects consisted of 187
      cases selected randomly from among the patients who attended Toho University
      Ohashi Hospital during a period of 1 year from January 1998. The values for urine
      basic fetoprotein (BFP) and polyamine and urinary cytology were examined.
      RESULTS: Urine BFP is considered useful for screening and monitoring urinary
      tract epithelial cancer as is urinary cytology. Urine BFP showed a statistically
      significant difference (P < 0.05) for G1 compared with urinary cytology and a
      significantly high level compared with urinary cytology as to the positive rate
      in the low stage group (P < 0.05). The positive rate of urine BFP was high in
      patients with urinary tract infection. CONCLUSION: Determining urine BFP, when
      combined with urinary cytology, is considered very useful for diagnosing patients
      with urinary tract epithelial cancer. This study suggests the possibility of
      urine BFP being superior to urinary cytology for screening early cancer and also
      as an indicator for observations on the clinical course.

PMID- 11328422
TI  - Endocrine therapy for recurrence after definitive radiotherapy in patients with
      prostate cancer.
AB  - BACKGROUND: Long-term results were analyzed to evaluate the role of endocrine
      therapy in the management of local and distant recurrence of prostate cancer
      following external radiation therapy. METHODS: Between 1976 and 1994, 92 patients
      with untreated prostate cancer underwent external beam radiation therapy alone.
      Endocrine therapy had been started when relapse was evident. RESULTS: Failure was
      seen in 35 of 92 patients: 10 local, 19 distant and six biochemical failures.
      Endocrine treatment was performed in 28 patients with nine local and 19 distant
      failures. The cancer-specific survival rate from the endocrine treatment was
      54.5% at 5 years. Prostate-specific antigen level in 20 of 20 patients (100%)
      decreased to below the normal limit 3 months after the start of endocrine
      therapy. In univariate analysis, T classification was the most significant
      variable for cancer-specific survival from the initial treatment. CONCLUSIONS: A
      favorable outcome was achieved by endocrine therapy in patients who had relapsed
      after external beam radiation monotherapy. Even the recurrent tumor had a
      sensitivity to androgen. Patients with locally advanced disease (T2b and T3) had
      poorer prognosis than those with minimally extended disease (T1b and T2a).

PMID- 11328423
TI  - Clomiphene citrate versus varicocelectomy in treatment of subclinical varicocele:
      a prospective randomized study.
AB  - BACKGROUND: The purpose of the study was to compare the effect of varicocelectomy
      with that of clomiphene citrate on seminal improvement and pregnancy rates in
      patients with subclinical varicocele. METHODS: A total of 42 infertile men with
      left subclinical varicocele were randomized to group I (21 patients, surgery) and
      group II (21 patients, medical therapy). The patients in group I were treated
      with varicocelectomy and those in group II with clomiphene citrate, 50 mg/day,
      orally. Sperm parameters (sperm density, motility and morphology) were recorded
      before and 6 months after beginning the treatment and pregnancy rates were
      estimated. In statistical analysis, paired and independent-samples t-tests,
      Kaplan-Meier and Log rank tests and Fisher's exact test were used. RESULTS: Mean
      +/- SD age of the series was 32.7 +/- 6.1 years, that of group I was 32.2 +/- 5.5
      years and that of group II was 33.1 +/- 6.7 years (P = 0.680). All seminal
      parameters increased after both surgical and medical treatment, but only
      increases in sperm density and motility following varicocelectomy were
      statistically significant. Changes in seminal parameters between groups I and II
      were statistically insignificant. Pregnancy was seen in two cases in group I and
      in one in group II (P = 0.500). The cumulative pregnancy rates were 12.5% in
      group I and 6.7% in group II (P = 0.589). CONCLUSIONS: Clomiphene citrate did not
      increase sperm density and motility as effectively as subclinical
      varicocelectomy, but there was no statistically significant difference between
      surgical and medical therapy methods in terms of seminal improvement and
      pregnancy rate.

PMID- 11328424
TI  - A simple and reliable monitoring system to confirm the preservation of the
      cavernous nerves.
AB  - BACKGROUND: It is important to establish a procedure with which to confirm the
      preservation of the cavernous nerves during nerve-sparing radical surgery. For
      this purpose, we examined changes in intracavernous pressure (ICP) following
      electrical stimulation of the neurovascular bundle (NVB) with respect to the
      continuity of the cavernous nerves. METHODS: Six cases of radical prostatectomy
      and eight cases of radical cystoprostatectomy were examined. In all cases, prior
      to prostate removal, electrical stimulation of the site where the NVB was
      determined to run was performed and the changes in ICP measured. In eight cases,
      ICP changes were also measured following prostate removal. RESULTS: Prior to
      prostate removal, ICP changes could be measured in all 28 sides of 14 cases.
      These changes were classified into two patterns: stimulation-related increases of
      convex waveform (t1) were observed in 24 sides (85.7%); and waveforms with
      reversed type (t2), which was thought to be an incomplete type t1, were observed
      in four sides (14.3%). There were no ICP changes following non-sparing or
      incomplete sparing of NVB macroanatomically. Of five sides where the NVB was
      supposedly completely preserved macroanatomically, ICP changes consisted of type
      t1 on three sides, t2 on one side and type t2 or no change on a single side. All
      measurements were obtained within 10 min. Neither electrical stimulation nor
      measurement of ICP caused any adverse effects. CONCLUSION: Intraoperative
      stimulation of the NVB while monitoring ICP changes provides a simple and
      reliable method of accurately evaluating the preservation of the cavernous
      nerves.

PMID- 11328425
TI  - Schinzel-Giedion syndrome.
AB  - A 2-month-old girl was brought to the Department of Pediatrics at Wakayama Rosai
      Hospital because of poor feeding since 1 month of age. She was the third child of
      young healthy non-consanguineous parents whose first son was healthy but whose
      second son had died of 18 trisomy. Physical examination showed midfacial
      hypoplasia with coarse dysmorphic features, choanal stenosis, remarkable
      abdominal distention and bilateral talipes equivarus. Abdominal ultrasonography,
      computed tomography and drip infusion pyelogram showed left severe hydronephrosis
      and right moderate hydronephrosis. Having diagnosed Schinzel-Giedion syndrome, a
      left ureteroneocystostomy with tailoring was performed to preserve renal
      functions and to eliminate the urinary tract infection at the age of 3 months.

PMID- 11328426
TI  - Renal angiomyolipoma associated with micronodular pneumocyte hyperplasia of the
      lung with tuberous sclerosis.
AB  - Tuberous sclerosis complex is an autosomal-dominant disorder characterized by the
      triad of mental retardation, epilepsy and adenoma sebaceum. Micronodular
      pneumocyte hyperplasia is a rare but distinctive pulmonary epithelial lesion,
      usually associated with tuberous sclerosis. To the authors' knowledge, the
      relationship between renal angiomyolipoma and micronodular pneumocyte hyperplasia
      in cases of tuberous sclerosis has not received attention in the urological
      literature. The case of a woman with renal angiomyolipomas associated with
      micronodular pneumocyte hyperplasia of the lung with tuberous sclerosis is
      reported here.

PMID- 11328427
TI  - Retrovesical desmoplastic small round cell tumor in a patient with urinary
      frequency.
AB  - A 21-year-old man with urological symptoms was found to have a large abdominal
      tumor in the retrovesical space between the bladder and the rectosigmoid colon.
      Radiologic findings revealed little evidence confirming the diagnosis. A
      transrectal biopsy failed to disclose the histopathologic origin of the tumor. An
      exploratory laparotomy with a complete surgical resection was impossible, so a
      wedge biopsy was performed. Combined histologic and immunohistochemical findings
      revealed the features of desmoplastic small round cell tumor (DSRCT). Despite
      subsequent multi-agent chemotherapy, the patient died as a result of the growing
      tumor and liver metastasis. There have been only two prior reports of this
      neoplasm in the urological literature.

PMID- 11328428
TI  - Neurofibroma of the bladder wall in von Recklinghausen's disease.
AB  - Neurofibromatosis, or von Recklinghausen's disease, is an autosomal dominant
      disease with multiple neurofibroma and cafe-au-lait spots. However, neurofibroma
      in the bladder wall is a rare condition in von Recklinghausen's disease. A 31
      year-old man with neurogenic voiding dysfunction due to sacral meningocele and
      acute urinary retention with neurofibroma of the bladder wall is presented with
      detailed radiologic evaluation. Patients with von Recklinghausen's disease should
      be carefully evaluated if urological symptoms exist.

PMID- 11328429
TI  - Deformation of the bladder due to collateral circulation caused by thrombosis of
      the left femoral vein.
AB  - A thrombus in the lower extremities as well as in its collateral circulation in
      the pelvis are not unusual conditions; however, bladder deformation due to such
      collateral circulation has not previously been reported. A case is presented of
      bladder deformation to the right due to collateral circulation caused by a
      thrombus in the lower left extremity in a 51-year-old man.

PMID- 11328430
TI  - Autohemicastration in a man without schizophrenia.
AB  - A 52-year-old unmarried bag craftsman was admitted to East Tokyo Metropolitan
      Hospital because of a large scrotal hematoma. He had accidentally hit his right
      testis against the edge of a desk early the previous morning. He had resected his
      right testis with scissors to release from severe pain 30 min after the accident.
      He had sutured the scrotal incision with two stitches of string by himself. At
      the emergency operation 36 h after the self-mutilation, we removed a hematoma
      weighing 283 g and ligated the cut end of the right spermatic cord after adequate
      debridement. He was diagnosed by a psychiatrist as having slightly low
      intelligence without psychotic disorder or drug abuse.

PMID- 11328432
TI  - A measure of critical care nurses' post-code stress.
AB  - AIM: The purpose of this research was to develop an instrument to measure
      critical care nurses' post-code stress and then to examine the psychometric
      properties. BACKGROUND: Critical care nurses experience stress from multiple
      sources. One source of stress may arise from participation in resuscitation
      attempts and this has been labelled post-code stress; however, no means exist for
      measuring this source of stress. DESIGN/METHOD: In phase 1, 47 items were
      developed and submitted to a panel of experts for content validity. Based on
      content experts' ratings, 20 items were retained for phase 2 instrument testing.
      To test the instrument, a convenience sample of critical care nurses was obtained
      from four institutions in north-eastern United States. Each nurse received the
      Post-Code Stress Scale and completed it anonymously. A subsample completed the
      Post-Code Stress Scale a second time to assess stability reliability. The Nursing
      Stress Scale was also administered to assess construct validity.
      RESULTS/FINDINGS: An exploratory principal components factor analysis with
      varimax rotation suggested five dimensions to post-code stress. These five
      dimensions accounted for 66% of the variance and indicated that stress arose from
      feeling discomposed, oppressed, uncertain, burdened and morally conflicted. The
      Pearson product moment correlation between the Post-Code Stress Scale and the
      Nursing Stress Scale was 0.46, providing preliminary evidence of construct
      validity. Internal consistency reliability estimates for the five-factor
      subscales ranged from 0.57 to 0.77 with only one factor being <0.70. The internal
      consistency reliability estimate for the final 14 items on the scale was 0.79.
      CONCLUSIONS: The instrument shows promise as a measure of post-code stress based
      on the evidence obtained in this study; however, further psychometric testing is
      warranted.

PMID- 11328433
TI  - The importance of conducting and reporting pilot studies: the example of the
      Scottish Births Survey.
AB  - BACKGROUND: In many research papers, pilot studies are only reported as a means
      of justifying the methods. This justification might refer to the overall research
      design, or simply to the validity and reliability of the research tools. It is
      unusual for reports of pilot studies to include practical problems faced by the
      researcher(s). Pilot studies are relevant to best practice in research, but their
      potential for other researchers appears to be ignored. OBJECTIVE: The primary aim
      of this study was to identify the most appropriate method for conducting a
      national survey of maternity care. METHODS: Pilot studies were conducted in five
      hospitals to establish the best of four possible methods of approaching women,
      distributing questionnaires and encouraging the return of these questionnaires.
      Variations in the pilot studies included (a) whether or not the questionnaires
      were anonymous, (b) the staff involved in distributing the questionnaires and (c)
      whether questionnaires were distributed via central or local processes. For this
      purpose, five maternity hospitals of different sizes in Scotland were included.
      RESULTS: Problems in contacting women as a result of changes in the Data
      Protection Act (1998) required us to rely heavily on service providers. However,
      this resulted in a number of difficulties. These included poor distribution rates
      in areas where distribution relied upon service providers, unauthorized changes
      to the study protocol and limited or inaccurate information regarding the numbers
      of questionnaires distributed. CONCLUSIONS: The pilot raised a number of
      fundamental issues related to the process of conducting a large-scale survey,
      including the method of distributing the questionnaire, gaining access to
      patients, and reliance on 'gatekeepers'. This paper highlights the lessons
      learned as well as the balancing act of using research methods in the most
      optimal way under the combined pressure of time, ethical considerations and the
      influences of stakeholders. Reporting the kinds of practical issues that occur
      during pilot studies might help others avoid similar pitfalls and mistakes.

PMID- 11328434
TI  - Psychometrics of a Chinese translation of the swallowing questionnaire.
AB  - AIMS OF THE STUDY: The purpose of this study was to determine the psychometric
      properties of a Chinese version of a swallowing questionnaire.
      BACKGROUND/RATIONALE: Impaired swallowing may lead to serious complications if
      health care professionals do not accurately assess the problem and promptly
      intervene. The recognition of symptoms indicative of a swallowing problem is
      essential for nurses. The swallowing questionnaire could provide nurses with a
      valid instrument to assess patients' impaired swallowing. DESIGNS/METHODS: Phase
      I consisted of experts doing the initial translation into Chinese and back
      translations of the questionnaire. Five experts then determined content validity
      of the Chinese version, and 35 bilingual subjects determined equivalence of the
      Chinese translation and English version. Phase II determined concurrent validity
      and internal consistency using 113 screened medical patients as subjects. Phase
      III used 105 screened long-term care subjects to determine construct validity.
      RESULTS/FINDINGS: In Phase I, rating on the appropriateness of items on the
      Chinese version yielding a content validity index of 0.988. The coefficient of
      equivalence between the Chinese and English versions of the instrument was 0.81,
      while per cent agreement for all items on the two versions ranged from 0.80-
      1.00. Phase II established internal consistency with a K-R20 of 0.74, and
      concurrent validity yielded a correlation between the swallowing questionnaire
      and the neurological swallowing exam of 0.675 (P < 0.01). Phase III determined
      construct validity with significant positive correlations found between the
      swallowing questionnaire and stroke history and masticatory ability. Significant
      negative correlations were found between swallowing and cognitive status,
      functional status and albumin. CONCLUSIONS: Although useful as a tool for nursing
      assessment and intervention, further work on the swallowing questionnaire such as
      conducting video fluoroscopy and a swallowing speed test, are recommended to
      further validate its accuracy.

PMID- 11328435
TI  - An assessment of the patients' needs in mental health education.
AB  - AIM OF THE STUDY: The aim of this study was to identify the specific educational
      needs of Chinese patients with schizophrenia using a Chinese version of the
      Educational Needs Questionnaire. BACKGROUND: Patient education provides adequate
      clinical information to patients, increases understanding of their illness
      condition and encourages their health-promoting behaviour. A full understanding
      and satisfaction of patient needs in relation to specific illness has played an
      important part in the development of an education programme for psychiatric
      patients. However, psychiatric patients' perceptions of their specific
      educational needs and whether or not these needs are being met have seldom been
      explored for the purposes of optimizing the effects of patient education
      programmes. This study served the purpose of assessing the learning needs of
      Chinese patients with schizophrenia in Hong Kong. DESIGN: A cross-sectional
      survey was conducted in Hong Kong with 192 Chinese outpatients with
      schizophrenia. The principles for determining the equivalence of translated tools
      were applied to the development of the Chinese version of the questionnaire.
      RESULTS: Patients gave high importance to gaining information about mental
      illness, strategies for improving social relationships and solving daily
      problems. Socioeconomic factors including education level and membership in a
      mutual support group correlated significantly with need importance and the unmet
      need score. Length of illness negatively correlated with need importance,
      indicating the adverse effect of illness on patients' interests in fulfilling
      needs. CONCLUSIONS: Assessment of mental health consumers' perceptions of their
      specific educational needs and tailoring patient educational curricula to the
      expressed needs appear essential. The importance of validity testing of a
      translated tool is also highlighted in this study.

PMID- 11328436
TI  - Chronic illness -- a disruption in life: identity-transformation among women with
      chronic fatigue syndrome and fibromyalgia.
AB  - BACKGROUND: People with chronic illnesses often suffer from identity-loss.
      Empirical research concerning patients with chronic fatigue syndrome (CFS) or
      fibromyalgia has not, however, adequately addressed the consequences of these
      illnesses for identity. AIM: The aim of this article is to describe how women
      with CFS and fibromyalgia create new concepts of identity after the onset of
      illness, and how they come to terms with their newly arisen identities. I aim to
      illuminate the biographical work done by these individuals, which includes a re
      evaluation of their former identity and life. This process is illustrated by the
      following themes: An earlier identity partly lost and Coming to terms with a new
      identity. METHOD: The study is based on interviews with 25 women in Sweden, 12
      with the diagnosis of CFS and 13 diagnosed with fibromyalgia. A grounded theory
      orientated approach was used when collecting and analysing the data. FINDINGS:
      The main findings are that: (1) the illnesses can involve a radical disruption in
      the women's biography that has profound consequences for their identity,
      particularly in relation to work and social life, (2) biographical disruptions
      are partial rather than total, calling for different degrees of identity
      transformation, (3) many of the women also experience illness gains in relation
      to the new identity. CONCLUSIONS: Thus, the biographical disruption and illness
      experience comprised both losses and illness gains that had consequences for
      identity.

PMID- 11328437
TI  - Adults' recollections of their experiences as young caregivers of family members
      with chronic physical illnesses.
AB  - AIMS OF THE STUDY: The aims of this study were to describe the number, kind, and
      intensity of caregiving activities performed by individuals who assumed
      caregiving responsibilities, as youngsters, for adults with chronic physical
      illnesses; to explore the meaning and effects of the caregiving experience on
      those individuals; and to examine positive and negative effects of caregiving
      then and now. BACKGROUND/RATIONALE: Family mobility, demographic changes, and
      health care system changes in the United States of America (USA) have contributed
      to an increasing number of youngsters under the age of 18 caring for adults with
      chronic physical illnesses in the home. The effects of such caregiving on
      youngsters and the long-term effects on them as adults require study.
      DESIGN/METHODS: This descriptive, retrospective study had a convenience sample of
      51 adults (age range 19--68 years now, 3--19 years then) who cared for their
      family members diagnosed with cancer, stroke, cardiovascular disease, multiple
      sclerosis or amyotrophic lateral sclerosis, respiratory disease, diabetes, or
      arthritis. Demographic data and caregiving data were analysed using descriptive
      statistics. The semistructured interview data were analysed using content
      analysis. RESULTS/FINDINGS: Of the caregiving care tasks most frequently
      performed, personal care was most difficult and household tasks were most time
      consuming. Family life, school, and time with friends were areas most likely to
      be affected by caregiving. Most subjects indicated they would permit their own
      children to assist with care as long as the youngster was not the sole caregiver.
      Youngsters need to be informed about the illness and caregiving tasks, have
      adequate support systems, and have some time to 'still be a child'. CONCLUSIONS:
      Professional caregivers should raise questions in their practice regarding
      involvement in caregiving by both adults and youngsters. If youngsters
      participate in caregiving in the home, they need to receive adequate information
      regarding care and the illness trajectory. Family-related research including the
      long-term effects of such experiences on the youngsters and their families is
      recommended.

PMID- 11328438
TI  - How do we facilitate carers' involvement in decision making?
AB  - BACKGROUND: Government health care policy urges service providers to involve
      service users in the decision-making process. Research studies have recommended
      changes to current health care practice to facilitate this involvement. However,
      carers' organizations continue to highlight a gap between policy and practice in
      relation to involvement. AIM: The aim of the study reported on in this paper was
      to investigate involvement in a specific health care context with a view to
      identifying both opportunities for change and practical, realistic ways of
      bringing about that change. This was a qualitative case study using a case study
      design. The field site selected was a respite and assessment (23 bedded) ward
      within the Psychiatric Unit of a hospital specializing in the care of older
      people. Informal carers (n=20) and members of the multidisciplinary team (n=29)
      were interviewed about their views and experiences. The interviews were
      audiorecorded and transcribed. Family meetings, multidisciplinary team meetings
      and ward routines were the focus of non-participant observation. Field notes from
      these observations, together with the interview data were analysed using constant
      comparative method. RESULTS AND CONCLUSIONS: The reported experiences of carers
      in this study highlighted four markers of satisfactory involvement: feeling that
      information is shared; feeling included in decision making; feeling that there is
      someone you can contact when you need to; and feeling that the service is
      responsive to your needs. The majority of carers felt dissatisfied with the level
      of involvement. The situation we found echoed that found in other studies, i.e.
      the majority of informal carers (henceforth 'carers') interviewed were
      dissatisfied with the level of their involvement. However, our investigation, in
      which the views of health care professionals as well as those of carers were
      sought, provided invaluable insight into why this might be the case. Two main
      sources of difficulty were found: hospital systems and processes, and the
      relationship between nursing staff and carers. The argument made is that
      practitioners themselves must notice and challenge these barriers if carer
      involvement is to be facilitated.

PMID- 11328439
TI  - Nurses' attitudes to terminally ill patients.
AB  - BACKGROUND: The care of terminally ill patients is a challenge for nurses that
      has raised special interest in recent years. Several studies have shown a
      stereotyped negative attitude in nurses towards terminally ill patients. However,
      all have used methods with several limitations. AIM: The aim of the study
      presented in this paper was to identify the nurses' attitude to the terminally
      ill patient in Catalonia, Spain, and the relationship of this attitude to
      different socio-demographic data (type of centre, shift, years of experience, age
      and sex) by means of a new quantitative method based on the free word-association
      test. METHODS: One hundred and seventy-five nurses working in 18 hospitals and
      hospices in Catalonia, Spain were included in the study. Data were analysed by
      the Associative Semantic Field Differential method by means of the computer
      programme CONTEXT and a quantitative evaluation of the degree of attitudes
      positivity was obtained. RESULTS: The study revealed a general slight negative
      trend in attitudes towards the terminally ill patient. A more positive attitude
      was observed in older caregivers and in women. The positivity in attitude
      decreased from morning to night shift. No differences were observed between
      nurses working in hospitals and those working in hospices. CONCLUSIONS: We
      conclude that nursing attitudes can be analysed by methods such as that used in
      this study. Attempts can be made to modify this attitude in caregivers by means
      of training programmes and stimulating awareness of an adequate professional
      approach.

PMID- 11328440
TI  - Changes in health visitors' work.
AB  - AIMS: The purpose of this investigation is to describe Scottish health visitors
      (HVs) experience of changes in their work and compare these with their Norwegian
      counterparts. BACKGROUND: The renewed emphasis on community health care, health
      promotion and illness prevention is a strong reason to focus on health visiting
      work. Knowledge about changes in practice are of special interest for nursing
      science as such knowledge could contribute to the development and advancement of
      the health visiting service. DESIGN: The study used a comparative descriptive
      design. The data are based upon in-depth interviews with nine HVs from Scotland
      and 12 HVs from Norway. RESULTS: The results showed similarities as well as
      differences. HVs in Scotland and Norway experienced changes in work load with
      decreases in some areas and increases in others, changes in work practice,
      approaches and techniques with more emphasis on clients' empowerment, and also
      fewer management positions held by nurses. The differences mainly related to the
      ways that the health visiting service had specialized and expanded. The aim of
      Scottish health visiting from 'cradle to grave' service was not adopted by the
      Norwegian HVs to the same extent. Scottish HVs specialized individually in some
      areas and used each other's competence to a much greater degree than the
      Norwegian HVs. CONCLUSIONS: It appeared that the Scottish HVs had found a path
      where health visiting work aimed at illness prevention and health promotion for
      everyone was on the way to becoming a comprehensive service and a stronger and
      more integrated part of the health visiting service. This is a pathway that
      Norwegian HVs still have to pursue. The qualitative approach and the slightly
      different samples limited the possibility for generalizations. Further research
      should address the question of changes and patterns in health visiting work, of
      how the development came about, and what are the bases for the differences in
      specialization and expansion of the service. Secondly it should be asked to what
      degree the development influences the quality of health visiting and consequences
      for clients, community and health visiting service.

PMID- 11328441
TI  - Corporate working in health visiting: a concept analysis.
AB  - AIM OF THE PAPER: The aim of this paper is to examine individualized health
      visiting care and compare it to corporate working within a consensual management
      style. Corporate working has been discussed and used in many different ways since
      the idea first came to light at the end of the 1980s. Resource management makes
      it an appealing model, however, analysing how corporate working functions in the
      practice setting reveals the complexity of this method of service provision.
      BACKGROUND: This paper is based on a method of practice developed by health
      visitors in Haywards Heath, West Sussex, who implemented the process. The article
      examines individualized health visiting care and compares it to corporate working
      within a consensual management style. Important in this analysis are the elements
      of reflexivity, active listening, reflection and the application of 'praxis'
      within the corporate caseload approach. METHODS: Rogers' evolutionary concept
      model was used to illuminate and explain the different ways of delivering the
      health visiting service. FINDINGS: There are benefits in working corporately:
      shared workload, increased professional support and improved accountability.
      Alongside the integrated supervision of this model is the opportunity offered to
      practitioners to innovate. This offsets any initial difficulty experienced in
      setting up this method and makes it a worthwhile change of style in health
      visiting practice. Improved service delivery, enhanced professional growth and
      increased opportunity for public health work can be demonstrated as outcomes of
      this model. For professionals this method may prevent 'burn-out', enhance
      practice and increase innovation in health visiting practice. Using this method
      as a blueprint, practitioners can develop their own style of corporate working
      that offers a service that is equitable, proactive, efficient and accessible to
      clients.

PMID- 11328442
TI  - Technology and humane nursing care: (ir)reconcilable or invented difference?
AB  - AIM(S) OF THE PAPER: This paper questions the validity of a boundary presumed to
      exist between technology and humane care. It argues the need for reconciliation
      of presumed tension(s) between technology and person focused care and the need to
      reconsider our ways of understanding the relations between technology and
      nursing. BACKGROUND/RATIONALE: Recent scholarship in the social sciences related
      to reproductive and imaging technologies and emergency resuscitation are examined
      and arguments are presented that question the appropriateness of a humanist view
      that emphasizes technology on the nonhuman and nonnatural side of a
      human/nonhuman, nature/artifice divide. It is argued that what determines
      experiences such as dehumanization is not technology per se but how individual
      technologies are used and operate in specific user contexts, the meanings that
      are attributed to them, how individuals or cultural groups define what is human,
      and the organizational, human, political and economic technological system
      (technique) that creates rationale and efficient order within nursing, health
      care and society. CONCLUSION: The paper concludes by asking whether the
      commonplace appeal to resolve tensions between humane care and technology has
      erroneously highlighted technology as the reason for impersonal care, and
      encourages re-examination of the relationship(s) between technology, humane care
      and nursing practice.

PMID- 11328443
TI  - Subject positions theory -- its application to understanding collaboration (and
      confrontation) in critical care.
AB  - BACKGROUND: Doctors and nurses do not usually take a collaborative approach to
      the ethical challenges of the critical care environment. This leads to the
      stresses that produce moral anguish and burnout -- both for nursing and medical
      staff. A more collegial relationship between nurses and physicians should improve
      patient care. If we are to promote this collegiality, one way to proceed is to
      investigate the interactions between health care professionals in order to
      develop an understanding of the barriers to, and supports for collaboration. AIM:
      Subject positions theory offers a method of explaining and elucidating the
      interactions between nurse and physician in terms of power dynamics, mutual
      expectations and the discourse available to each individual. This paper aims to
      demonstrate how subject positions theory can facilitate the interpretation of the
      interactions between health professionals in terms of the power dynamics
      influencing those interactions. DISCUSSION: This paper will use the example of a
      case study from my own research to demonstrate the application of this theory and
      its usefulness in the analysis of the interactions between health care
      professionals. CONCLUSIONS: Application of this theory is used to demonstrate the
      author's argument that the current political and cultural structure of the health
      care system does not support the subject position - nurse advocate.

PMID- 11328444
TI  - Burnout in psychiatric nursing.
AB  - INTRODUCTION: Burnout in nursing is of both individual and organizational concern
      with ramifications for well-being, job performance, absenteeism and turnover.
      Burnout is rarely assessed as part of a comprehensive model of occupational
      stress, a short-coming which this paper attempts to redress. METHOD: A randomly
      selected sample of 510 psychiatric nurses from one Scottish Trust completed a
      questionnaire based on a psychological model of occupational stress which
      included the Maslach Burnout Inventory (MBI) as the dependent variable. FINDINGS:
      The respondents reported average, low and average levels of emotional exhaustion,
      depersonalization and personal accomplishment, respectively. The study sample had
      significantly lower scores on emotional exhaustion and depersonalization than
      normative data but also significantly lower levels of personal accomplishment
      than a normative group of physicians and nurses. Only 2.0% of the study sample
      could be categorized as having high burnout overall (i.e. high emotional
      exhaustion, high depersonalization, low personal accomplishment) and they
      differed significantly from the rest only in terms of males being over
      represented. Hierarchical regression analysis revealed that selected explanatory
      variables accounted for 41.9% of emotional exhaustion, 16.4% of depersonalization
      and 25.6% of personal accomplishment in the study sample. IMPLICATIONS: The paper
      discusses the implications of the findings in terms of a comprehensive approach
      to intervention aimed at minimizing the risk of burnout in psychiatric nurses.
      Such an approach will involve interventions at the organizational and individual
      level.

PMID- 11328445
TI  - The relationship between support and stress in forensic community mental health
      nursing.
AB  - AIMS OF THE STUDY/PAPER: This paper reports the results of a survey of forensic
      community mental health nurses (FCMHNs) in England and Wales which aimed to
      ascertain the level of stress and burnout experienced by this group.
      BACKGROUND/RATIONALE: Several studies have identified that mental health nursing
      is a stressful activity and the relationship between factors such as age,
      experience, support, caseload size and perceived stress have been explored.
      However, until recently, no studies have examined the situation of FCMHNs and
      this paper extends the analysis of studies completed by the main author,
      considering issues related to coping abilities and support systems.
      DESIGN/METHODS: The survey involved respondents completing a demographic
      questionnaire and a range of standardized validated measures (Maslach Burnout
      Inventory, General Health Questionnaire and Community Psychiatric Nurse Stress
      Questionnaire). The population for the study was all identified FCMHNs attached
      to the 26 National Health Service (NHS) Medium Secure Units in England and Wales
      (n=104). RESULTS/FINDINGS: A high response rate of 77% (n=80) was achieved. The
      results identified that a number of respondents were experiencing burnout.
      Statistically significant associations were found between caseload size and level
      of stress. The results also suggest that support from managers and colleagues
      were an important factor in ameliorating the experience of stress and show that
      individuals in this study experiencing high levels of stress adopted palliative
      behaviours such as use of alcohol. CONCLUSIONS: The paper concludes by suggesting
      that such findings should be considered when delivering stress management
      programmes and reinforce the potential benefit of effective clinical supervision
      as a means of staff support.

PMID- 11328446
TI  - The lived experience of clinical development unit (nursing) leadership in Western
      Sydney, Australia.
AB  - BACKGROUND: A network of nine Clinical Development Units (Nursing) (CDU(N)) were
      recently created in the Western Sydney Area Health Service. These units are
      designed to develop patient-focused nursing practice through group process and
      action research, based on principles of transformational leadership. AIMS OF THE
      STUDY: Although there is documented evidence from Australia and the United
      Kingdom (UK) that CDUs and Nursing Development Units (NDUs) are very successful
      in improving both patient and staff satisfaction, there is also growing evidence
      that the stressors experienced by nurse leaders are threatening the survival of
      some of these units. This study set out to develop an understanding of the
      phenomena of Clinical Development Unit (Nursing) leadership when these stressors
      were likely to impinge. STUDY DESIGN: Hermeneutic phenomenology was employed in
      order to identify how these experiences changed over time. Two rounds of
      interviews were conducted: approximately 4--6 months after the launch and, again,
      12 months later. FINDINGS: The Clinical Development Unit (Nursing) philosophy
      provided a framework on which these very motivated leaders began to enhance
      nursing accountability in their units through reflective practice and
      participatory governance. While reinforcing many previously published positive
      and negative aspects of Clinical Development Units and Nursing Development Units,
      this paper also highlights how the expectations and experiences of these leaders
      changed over time with unanticipated pressures of work, a high turnover of
      clinical leaders, a perceived diminution of management support and unrealistic
      self-expectations. A significant theme that emerged as these stressors began to
      impinge was the leaders' own need for leadership in order to sustain their
      confidence and motivation. IMPLICATIONS FOR NURSING: Insights harvested from this
      study have since been incorporated into a revised leadership preparation
      programme and support mechanisms for the leaders of eight new Clinical
      Development Units (Nursing) in the Western Sydney Area Health Service.

PMID- 11328448
TI  - Changes in preoptic and hypothalamic levels of progesterone receptor mRNA across
      the oestrous cycle of the ewe.
AB  - We measured the levels of progesterone receptor (PR) mRNA in the hypothalamus and
      preoptic area (POA) of the ewe across the oestrous cycle. Perfusion-fixed
      hypothalamic tissue was collected from sheep killed during the luteal and
      follicular phases and during behavioural oestrus. Blood samples taken at the time
      of tissue collection verified that the oestrous ewes were undergoing a
      preovulatory luteinizing hormone (LH) surge. Matched sections were taken from the
      POA, periventricular nucleus (PeVN), ventromedial nucleus (VMN) and arcuate
      nucleus of each animal. In situ hybridization was performed using a sheep
      specific, (35)S-labelled riboprobe for PR and semiquantitative image analysis was
      conducted on emulsion-dipped slides. The number of silver grains per cell was
      greater in the VMN and arcuate nucleus of oestrous ewes than in luteal and
      follicular phase ewes; there was no cyclic variation in the level of PR mRNA
      expression in the cells of the POA and PeVN. The number of labelled cells per mm2
      in the VMN was higher in the oestrous ewes than in luteal phase and follicular
      phase ewes. The number of labelled cells in the PeVN was also higher in the
      oestrous ewes than in follicular phase ewes, but there was no cyclic variation in
      the POA and arcuate nucleus. In the ewe, the onset of behavioural oestrus
      corresponds to the onset of the preovulatory LH surge and increased PR mRNA
      expression at this time is likely to be due to the high concentrations of
      circulating oestrogen that precede this period.

PMID- 11328447
TI  - Effects of serotonin, GABA and neuropeptide Y on seabream gonadotropin releasing
      hormone release in vitro from preoptic-anterior hypothalamus and pituitary of red
      seabream, Pagrus major.
AB  - The effects of serotonin (5-HT), GABA and neuropeptide Y (NPY) on in vitro
      release of seabream (sb) gonadotropin releasing hormone (GnRH) from slices of the
      preoptic-anterior hypothalamus (P-AH) and pituitary of red seabream were studied.
      5-HT, GABA and NPY all stimulated the release of sbGnRH from the P-AH but not
      from the pituitary of immature red seabream. They also stimulated sbGnRH release
      from the P-AH with a similar potency during the course of gonadal development.
      Specific agonists and/or antagonists of 5-HT, GABA and NPY showed that 5-HT and
      GABA utilize 5-HT(2) and GABAA receptor subtypes, respectively, to mediate their
      action, and that NPY employs at least NPY(Y1) and NPY(Y2) receptor subtypes to
      stimulate sbGnRH release. Combinations of different antagonists for 5-HT, GABA
      and noradrenaline/adrenaline did not block the stimulatory influence of NPY on
      release of sbGnRH, indicating that the action of NPY on the sbGnRH neuronal
      system is probably direct.

PMID- 11328449
TI  - Differences in arginine vasotocin gene transcripts and cortisol secretion in
      trout with high or low endogenous melanin-concentrating hormone secretion.
AB  - Previous studies on trout suggest that melanin-concentrating hormone (MCH) acts
      at both hypothalamic and pituitary levels to restrain the release of
      adrenocorticotropic hormone and hence cortisol during stress. Using in situ
      hybridization, the present work examined whether high rates of MCH secretion were
      associated with changes in the synthesis of arginine vasotocin (AVT), one of the
      corticotropin secretogogues. It also examined whether high endogenous MCH
      secretion restrains cortisol secretion during intense as well as mild stress, and
      how exogenous MCH affects the rise in plasma cortisol following injection stress.
      Trout were reared in black- or white-coloured tanks for 1 year or more to achieve
      maximal differences in MCH secretion. Following a mild stress, cortisol secretion
      was greater in black-reared fish with low MCH secretion which is in line with
      previous findings but, following a more severe stress, plasma cortisol
      concentrations were similar in the two groups. Injection of MCH into black
      adapted fish restrained the stress-induced rise in plasma cortisol concentration
      during the first hour but did not affect final cortisol values. In two separate
      experiments, AVT mRNA levels were significantly lower in the hypothalamus of
      black-reared fish. Possible explanations for this include a greater negative
      feedback restraint by cortisol, which is likely to rise higher in black-adapted
      fish during the moderate, daily stresses of aquarium life; or the possibility
      that exposure to a white background may be psychologically stressful, stimulating
      AVT transcription. The possibility that MCH directly stimulates AVT transcription
      cannot be excluded but seems less likely. The results suggest that while MCH may
      restrain the release of hypothalamo-pituitary stress hormones under moderately
      stressful conditions, it does not restrain AVT synthesis.

PMID- 11328450
TI  - Seasonal regulation of membrane and intracellular corticosteroid receptors in the
      house sparrow brain.
AB  - A number of studies have demonstrated seasonal regulation of the adrenocortical
      response to stress, or of corticosteroid binding globulins, but very few studies
      have examined seasonal regulation of corticosteroid receptor levels. As a result,
      there have been few attempts to produce an integrated picture of seasonal
      plasticity of the stress response. We measured baseline and stress-induced
      corticosterone (CORT), corticosteroid binding globulin and neuronal cytosolic and
      membrane corticosteroid receptor levels in male and female, wild-caught house
      sparrows (Passer domesticus) during three different seasons over the annual cycle
      (nesting, molting and winter). We identified three neuronal corticosteroid
      receptors in the house sparrow brain: two intracellular receptors and one
      membrane-associated receptor. Little is known about corticosteroid receptors in
      neuronal membranes of avian and mammalian species, but we found that the levels
      of membrane corticosteroid receptors varied seasonally, being lowest during the
      nesting season. Cytosolic corticosteroid receptor numbers (both low and high
      affinity receptors) also varied seasonally. In contrast to the membrane bound
      receptors, however, the numbers of low and high affinity cytosolic receptors were
      lowest during winter. In addition, mean levels of total basal and stress-induced
      CORT in the plasma varied seasonally. Both basal and stress-induced levels of
      total CORT were significantly higher during nesting than during winter or molt.
      Finally, corticosteroid binding globulin levels in plasma were also seasonally
      regulated, in a pattern similar to total CORT, so that estimated free CORT levels
      did not vary between seasons. These data indicate that multiple components of the
      stress response are seasonally regulated in birds obtained from wild populations.
      Interactions between these regulated components provide a basis for seasonal
      differences in behavioural and physiological responses to stress.

PMID- 11328451
TI  - Central orexin-A activates hypothalamic-pituitary-adrenal axis and stimulates
      hypothalamic corticotropin releasing factor and arginine vasopressin neurones in
      conscious rats.
AB  - The effects of centrally injected orexin-A on plasma adrenocorticotropin (ACTH)
      and corticosterone levels and corticotropin releasing factor (CRF) and arginine
      vasopressin (AVP) mRNA in the parvocellular cells of the paraventricular nucleus
      (PVN) of the rat were investigated. In animals implanted previously with a
      lateral brain ventricle and femoral artery cannula, a single i.c.v. injection of
      orexin-A (10 microg/rat) resulted in a rapid, significant increase in plasma ACTH
      and corticosterone concentrations. Plasma ACTH reached a peak (12.5-fold greater
      than basal levels) at 30 min, which was maintained over 120 min before declining
      towards control levels by 240 min. Plasma corticosterone concentrations reached a
      peak (6.7-fold greater than basal levels) at 30 min. Orexin-A at a higher dose
      (30 microg/rat) also produced a rapid increase in plasma ACTH and corticosterone
      concentrations. The area under the curve for plasma levels of ACTH was similar
      for both doses of orexin-A. In a second study, orexin-A (10 microg/rat) was
      injected i.c.v. and brains and pituitaries were rapidly removed after 240 min. In
      situ hybridization histochemistry revealed that CRF and AVP mRNA levels were
      significantly increased in the parvocellular cells of the PVN. Pro
      opiomelanocortin mRNA levels in the pituitary gland were not significantly
      elevated in response to orexin-A. These results suggest that orexin-A is able to
      act centrally to activate the hypothalamic-pituitary-adrenal axis involving
      stimulation of both CRF and AVP expression.

PMID- 11328452
TI  - Repeated antenatal glucocorticoid treatment decreases hypothalamic corticotropin
      releasing hormone mRNA but not corticosteroid receptor mRNA expression in the
      fetal guinea-pig brain.
AB  - Approximately 10% of pregnant women are treated with synthetic glucocorticoids in
      late gestation, to promote fetal lung maturation. The effectiveness of this
      treatment has led to the use of repeated dose regimens, with little knowledge of
      the impact on neuroendocrine development. Animal studies have recently shown that
      repeated fetal glucocorticoid exposure can lead to permanent changes in
      hypothalamic-pituitary-adrenal (HPA) function in offspring. In this study, we
      hypothesized that such treatment modifies corticotropin releasing hormone (CRH),
      glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) systems in the
      developing limbic system and hypothalamus. Pregnant guinea-pigs were treated with
      dexamethasone, betamethasone or vehicle on days 40,41,50,51,60 and 61 of
      gestation (birth = 68 days). On day 62, guinea-pigs were killed and the fetuses
      rapidly removed. Glucocorticoid treatment resulted in a dose-dependent reduction
      in plasma cortisol concentrations in both male and female fetuses. There was also
      a significant reduction in CRH mRNA expression in the hypothalamic
      paraventricular nucleus. In contrast, exposure to glucocorticoid increased MR
      mRNA expression in the hippocampus (CA1/2 and CA3) and dentate gyrus of female
      fetuses. There was a small but significant increase in GR mRNA expression in
      limbic structures in male fetuses following treatment with 1 mg/kg dexamethasone.
      However, there was no significant effect of glucocorticoid exposure on
      hippocampal GR mRNA expression in female fetuses, or hypothalamic GR mRNA in
      either males or females. In conclusion, repeated maternal glucocorticoid
      treatment inhibits fetal HPA function. The fact that CRH mRNA levels were reduced
      indicates that synthetic glucocorticoids enter the fetal brain. By contrast,
      fetal glucocorticoid exposure does not downregulate GR mRNA, and increases MR
      mRNA expression. The latter likely reflects removal of circulating endogenous
      ligand (cortisol). These alterations may form the basis for permanently modified
      HPA activity in later life.

PMID- 11328453
TI  - Identification of efferent neural pathways from the lamina terminalis activated
      by blood-borne relaxin.
AB  - The ovarian hormone relaxin, in addition to its role in pregnancy, exerts an
      action on the brain to influence oxytocin and vasopressin secretion, water
      drinking, and cardiovascular function. Intravenous (i.v.) infusion of relaxin
      causes an acute water drinking response, confirming its role as a dipsogenic
      hormone. The aim of this study was to determine whether neurones in the lamina
      terminalis, which project to the hypothalamic paraventricular and supraoptic
      nuclei, are activated by elevated levels of circulating relaxin in conscious
      rats. Immunocytochemistry combined with retrograde neuronal tracing with cholera
      toxin B subunit conjugated to cholera toxin B (CTB-gold) was used to identify
      populations of neurones responding with elevated cells of Fos protein to i.v.
      relaxin administration and which project to these specific hypothalamic sites.
      Neurones exhibiting Fos were present in the outer parts of the subfornical organ
      (SFO), the dorsal part of the organum vasculosum (OVLT), the supraoptic nucleus
      and the paraventricular nucleus. These did not occur in control rats with i.v.
      infusions of isotonic saline. Approximately 90% of neurones concentrated in the
      outer parts of the SFO and in the dorsal OVLT showed both retrogradely
      transported CTB-gold and Fos in response to i.v. infusion of relaxin. These data
      support a role for relaxin acting on the brain to regulate body fluid and
      electrolyte homeostasis by activating neural pathways subserving water drinking,
      vasopressin and oxytocin secretion.

PMID- 11328454
TI  - The role of neuropeptide Y in orexin-induced hypothalamic-pituitary-adrenal
      activation.
AB  - The role of neuropeptide Y (NPY) in the mediation of orexin-induced hypothalamic
      pituitary-adrenal (HPA) activation was investigated in the rat. The HPA system
      was stimulated by intracerebroventricular (i.c.v.) administration of orexin-A or
      orexin-B (140 or 280 pmol, respectively) and the plasma concentration of
      corticosterone was used as an index of the degree of activation. i.c.v.
      pretreatment with NPY antagonist or NPY antiserum (30 min or 24 h before orexin
      administration, respectively) inhibited the orexin-induced corticosterone
      release. The inhibitory actions of the antagonist and the antiserum were revealed
      by the dose-response curve; the highest concentrations practically abolished the
      HPA activation evoked by the orexins. These data suggest that the HPA system
      stimulating effect of the orexins may be mediated by NPY.

PMID- 11328455
TI  - Androgens alter corticotropin releasing hormone and arginine vasopressin mRNA
      within forebrain sites known to regulate activity in the hypothalamic-pituitary
      adrenal axis.
AB  - To reveal direct effects of androgens, independent of glucocorticoids, we studied
      the effects of gonadectomy (GDX) in adrenalectomized (ADX) rats with or without
      androgen replacement on corticotropin releasing hormone (CRH) and arginine
      vasopressin (AVP) mRNA expression within various forebrain sites known to
      regulate the hypothalamic-pituitary-adrenal axis. These included the medial
      parvocellular portion of the paraventricular nucleus of the hypothalamus (mp
      PVN), the central and medial nuclei of the amygdala and bed nuclei of the stria
      terminalis (BNST). In the mp PVN, ADX stimulated both CRH and AVP mRNA
      expression. Combined ADX + GDX inhibited only AVP, and testosterone and
      dihydrotestosterone (DHT) restored AVP mRNA. In the central nucleus of the
      amygdala, ADX decreased CRH mRNA expression, and this response was unaffected by
      GDX +/- testosterone or DHT replacement. In the medial amygdala, AVP mRNA
      expression was decreased by ADX, abolished by ADX + GDX, and restored by androgen
      replacement. ADX had no effect on CRH and AVP mRNA expression in the BNST. GDX +
      ADX, however, reduced CRH mRNA expression only within the fusiform nuclei of the
      BNST and reduced the number of AVP-expressing neurones in the posterior BNST.
      Androgen replacement reversed both responses. In summary, in ADX rats, AVP, but
      not CRH mRNA expression in the amygdala and mp PVN, is sensitive to GDX +/-
      androgen replacement. Both CRH- and AVP-expressing neurones in the BNST respond
      to GDX and androgen replacement, but not to ADX alone. Because androgen receptors
      are not expressed by hypophysiotropic PVN neurones, we conclude that
      glucocorticoid-independent, androgenic influences on medial parvocellular AVP
      mRNA expression are mediated upstream from the PVN, and may involve AVP-related
      pathways in the medial amygdala, relayed to and through CRH- and AVP-expressing
      neurones of the BNST.

PMID- 11328456
TI  - Localization of the melatonin-related receptor in the rodent brain and peripheral
      tissues.
AB  - Previous studies have provided a limited examination of the expression of the
      orphan melatonin-related receptor in the pituitary and hypothalamus of human and
      sheep and retinal tissue in the sheep. The present study reports evidence of
      conservation of expression in regions of the hypothalamus (dorsal medial
      hypothalamus, lateral hypothalamus, arcuate nucleus), the epithelial layer lining
      the third ventricle and the paraventricular thalamic nucleus of the mouse, rat
      and hamster. An extensive and detailed analysis of melatonin-related receptor
      mRNA expression in the mouse central nervous system and peripheral tissues is
      presented. Mapping the distribution throughout the entire mouse brain has
      revealed new sites of expression in a number of brain nuclei, including preoptic
      areas, parabrachial nuclei and widespread distribution in the olfactory bulb.
      Reverse transcriptase-polymerase chain reaction was performed with RNA isolated
      from peripheral tissues revealing expression of the melatonin-related receptor
      mRNA in the mouse kidney, adrenal gland, intestine, stomach, heart, lung, skin,
      testis and ovary. These results suggest a conserved function in neuroendocrine
      regulation and a potential role in coordinating physiological responses in the
      central nervous system and peripheral tissues.

PMID- 11328457
TI  - Calcium-dependent effects of melatonin inhibition of glutamatergic response in
      rat striatum.
AB  - The effects of melatonin, amlodipine, diltiazem (L-type Ca2+ channel blockers)
      and omega-conotoxin (N-type Ca2+ channel blocker) on the glutamate-dependent
      excitatory response of striatal neurones to sensory-motor cortex stimulation was
      studied in a total of 111 neurones. Iontophoresis of melatonin produced a
      significant attenuation of the excitatory response in 85.2% of the neurones with
      a latency period of 2 min. Iontophoresis of either L- or N-type Ca2+ channel
      blocker also produced a significant attenuation of the excitatory response in
      more than 50% of the recorded neurones without significant latency. The
      simultaneous iontophoresis of melatonin + amlodipine or melatonin + diltiazem did
      not increase the attenuation produced by melatonin alone. However, the
      attenuation of the excitatory response was significantly higher after ejecting
      melatonin + omega-conotoxin than after ejecting melatonin alone. The melatonin
      Ca2+ relationship was further supported by iontophoresis of the Ca2+ ionophore A
      23187, which suppressed the inhibitory effect of either melatonin or Ca2+
      antagonists. In addition, in synaptosomes prepared from rat striatum, melatonin
      produced a decrease in the Ca2+ influx measured by Fura-2AM fluorescence. Binding
      experiments with [3H]MK-801 in membrane preparations from rat striatum showed
      that melatonin did not compete with the MK-801 binding sites themselves although,
      in the presence of Mg2+, melatonin increased the affinity of MK-801. The results
      suggest that decreased Ca2+ influx is involved in the inhibitory effects of
      melatonin on the glutamatergic activity of rat striatum.

PMID- 11328458
TI  - Adrenomedullin acts in the rat paraventricular nucleus to decrease blood
      pressure.
AB  - Adrenomedullin is a recently discovered peptide involved in the control of fluid
      and electrolyte homeostasis and cardiovascular function through peripheral and
      central nervous system actions. The present study was undertaken to examine the
      cardiovascular effects of adrenomedullin microinjection directly into the
      paraventricular nucleus (PVN). Microinjection of adrenomedullin into the PVN of
      urethane anaesthetized male Sprague-Dawley rats resulted in site-specific,
      repeatable decreases in blood pressure. These hypotensive effects were found to
      be dose related, and were not mediated by activation of calcitonin gene-related
      peptide receptors. These data suggest that adrenomedullin influences
      cardiovascular regulation through receptor mediated actions at the PVN of the
      hypothalamus.

PMID- 11328459
TI  - Maintaining cell sensitivity to G-protein coupled receptor agonists: neurotensin
      and the role of receptor gene activation.
AB  - In the last few years, a number of studies have brought new insights into the
      fundamental mechanisms of cell desensitization and internalization of G-protein
      coupled receptors. Such studies have demonstrated that cells remain desensitized
      from a few minutes to several hours, after exposure to high concentrations of
      agonist. However, in vivo, agonists such as hormones are always present, even in
      small amounts, and such long desensitization is not conceivable, since constant
      stimulation of cells is required for physiological responses. Under such
      circumstances, cells would require a means to permanently maintain sensitivity to
      various internal or external stimuli. In the present review, we have taken as an
      example the expression of the high affinity neurotensin receptor, a seven
      transmembrane G-protein coupled receptor, upon prolonged exposure to its agonist,
      and observed that cells remained sensitive only if the receptor gene was
      activated by the agonist. Consequently, new receptors were synthesized, and
      either delivered to the cell surface or accumulated in submembrane pools. This
      regulation takes place only after prolonged and intense agonist stimulation.
      Under these conditions, it is proposed that receptor turnover is accelerated in
      proportion to the agonist concentration in order to allow the cells to produce an
      adapted cellular response to external stimuli. Such mechanisms thus play a key
      role in cell sensitivity to hormones.

PMID- 11328460
TI  - Practical aims to maintain neonatal resuscitation skills.

PMID- 11328461
TI  - Antimicrobials in the management of invasive meningococcal disease.

PMID- 11328462
TI  - Impact and aetiology of respiratory infections, asthma and airway disease in
      Australian Aborigines.
AB  - In this review, we describe the burden of respiratory illness in Australian
      indigenous communities and examine evidence of aetiology. We have reviewed the
      results from studies of respiratory infections and asthma-like symptoms conducted
      in remote and non-remote indigenous communities and contrasted them with data
      from comparable studies in non-indigenous communities. Although bias cannot be
      controlled and generalizability is an issue, the data are the only information
      available and, as such, provide a basis for a hypothesis generating approach to
      better health care. The evidence suggests that many indigenous people, especially
      those who live in non-remote regions, have asthma-like symptoms that are largely
      of an infectious rather than an allergic origin. Moreover, indigenous communities
      continue to be exposed to low immunisation rates, to have low rates of
      breastfeeding and to have high rates of cigarette smoking, all of which have the
      potential to increase the prevalence of respiratory illnesses. It is important to
      identify the most effective treatments and preventive strategies for respiratory
      symptoms that are prevalent in indigenous children. Respiratory symptoms that are
      largely of a bacterial-infectious origin may not benefit from commonly prescribed
      asthma therapies and, without appropriate treatment, may lead to ongoing health
      problems.

PMID- 11328463
TI  - Why paediatricians rural out going to the country but support opportunities for
      change.
AB  - OBJECTIVES: To determine the knowledge of vacant country specialist positions,
      the main barriers to filling country specialist positions, the acceptance of
      hypothetical creative employment models and to gain understanding of what would
      it take for respondents to accept a country position. METHODOLOGY: Mailed self
      report questionnaires to all 103 Queensland paediatricians and finishing
      paediatric trainees (response rate 93.1%) to explore reasons for the long-term
      vacancy of the Staff Paediatrician position at the Mount Isa Base Hospital, North
      west Queensland, Australia. RESULTS: Of the respondents, 87.4% were aware of the
      vacant position. The lack of adequate locum cover for leave (97.8%), on-call load
      (92.2%), professional isolation (91.4%), and family commitments (91.4%) were
      identified as the four most frequently recognized recruitment barriers. Of the
      respondents, 30.2% said they could be attracted to such a position if they were
      guaranteed the ability to return to their present post in 2 years, 30.7% said
      they could be attracted to a rural exchange, and 73.1% suggested the position
      would be more attractive to new Fellows if at the end of a 2-year period they
      were guaranteed some Visiting Medical Officer sessions or a temporary Staff
      Paediatrician position at a tertiary centre. Significantly, fewer of the 30-39
      years age group said available job opportunities for their spouse made it
      impossible for them to consider the advertised position, compared to older age
      groups (P = 0.003). In response to the question 'What would it take for you to
      consider such a position?', 22.6% answered a change in employment package, 22.6%
      a change in family commitments, 16.6% too subspecialized, and 7.1% could possibly
      consider a locum or exchange in the future. CONCLUSIONS: Specialist positions,
      such as the advertised position, are well known, but remain unfilled because they
      are considered unsustainable. However, the response to hypothetical creative
      employment models suggests this could be changed, provided specialist training
      (e.g. paediatric training) is kept general and the younger consultant is given
      consideration.

PMID- 11328464
TI  - Neonatal resuscitation training program in Malaysia: results of the first 2
      years.
AB  - OBJECTIVES: To determine the number of providers and instructors trained by the
      initial 37 core instructors during the first 2 years following the launch of the
      Malaysian Neonatal Resuscitation Program (NRP). To identify remediable problems
      which interfered with the propagation of the NRP in Malaysia. METHODOLOGY: A
      prospective observational study carried out over a 2-year period between 2
      September 1996 to 2 September 1998. For every training course conducted, the
      instructors completed a NRP course report form (Form A) that documented the
      instructors involved in the course. For every participant who attended the course
      and successfully completed it, the instructors submitted a record form (Form B)
      that contained the name, hospital address, department, profession, place of work,
      language used for training and the marks obtained by the individual participant.
      After each course, completed forms A and B were returned to the NRP secretariat
      for compilation. RESULTS: Of the 37 core instructors, 35 (94.6%) carried out
      training courses in their respective home states. A further 513 new instructors
      and 2256 providers were trained subsequently. A total of 2806 health personnel
      from all 13 states of Malaysia were NRP-certified during the first 2 years.
      However, 61.2% (n = 335) of the 550 instructors were inactive trainers, having
      trained less than four personnel per instructor a year. Most of the NRP-certified
      personnel were either doctors (32.0%) or nursing staff (64.4%). More than 60% of
      these worked either in the labour rooms, neonatal intensive care units or special
      care nurseries. At least one person from all three university hospitals and all
      general hospitals, 89.3% (92/103) of the district hospitals, 3.5% (73/2090) of
      the maternal and child health services, and 21% (46/219) of the private hospitals
      and maternity homes, were trained in the NRP. CONCLUSION: Dissemination of the
      NRP in Malaysia during the first 2 years was very encouraging. Further efforts
      should be made to spread the program to private hospitals and the maternal and
      child health services. In view of the large number of inactive instructors, the
      criteria for future selection of instructors should be more stringent.

PMID- 11328465
TI  - A parent-completed developmental questionnaire: follow up of ex-premature
      infants.
AB  - OBJECTIVE: Premature infants are at increased risk of developmental disability.
      Early identification of problems allows intervention to ameliorate or attenuate
      problems. A reliable screening tool allows triage of children in this high-risk
      population by identifying those unlikely to need full developmental assessment.
      To explore the test characteristics of an established parent-completed
      developmental assessment questionnaire 'Ages and Stages Questionnaire' (ASQ) in
      follow up of an Australian population of premature infants. METHODOLOGY: One
      hundred and sixty-seven children born prematurely with corrected ages 12- to 48
      months attending the Growth and Development Clinic at the Mater Children's
      Hospital in Brisbane, Queensland, Australia; 136 questionnaires 'ASQ' were
      returned completed (81%) and were compared to formal psychometric assessment
      (Griffith Mental Development Scales for 12- and 24-months, Bayley Mental
      Development Intelligence Scale for 18-months, McCarthy General Cognitive
      Intelligence Scale for 48-months). Developmental delay was considered to be
      present if any of the above psychometric assessments fell below 1.0 standard
      deviations (SD). The ASQ cut-off used was 2.0 SD (US data derived means and SD).
      RESULTS: Aggregate results for all age groups comparing ASQ to psychometric
      assessments as 'gold standards' found the ASQ to have the following test
      characteristics: sensitivity (90%); specificity (77%); positive predictive value
      (40%); negative predictive value (98%); % over-referred (20%); % under-referred
      (1%); % agreement (79%). Likelihood ratio for children failing the ASQ was 3.8
      and for passing the ASQ was 0.13. Twenty-one children with known disabilities
      were included in the study and in 14 of these, the ASQ overall score agreed with
      the psychometric assessment (67%). CONCLUSION: The high negative predictive value
      of the ASQ supports its use as a screening tool for cognitive and motor delays in
      the follow up of ex-premature infants. This would need to be combined with other
      strategies as part of a comprehensive follow up program for ex-premature infants.

PMID- 11328466
TI  - Burkholderia cepacia in cystic fibrosis: novel Australian cluster strain without
      accelerated respiratory deterioration.
AB  - OBJECTIVE: To determine whether 4 years of colonization with a novel Australian
      cluster strain (The 'Hunter' strain) of Burkholderia cepacia (B. cepacia) in
      cystic fibrosis (CF) patients was associated with more rapid decline in
      nutritional status and pulmonary function than in non-colonized contemporaries
      from the same CF clinic. METHODOLOGY: A retrospective review of respiratory
      function and nutritional data from a single multidisciplinary paediatric CF
      clinic over 4 years (1993-97). RESULTS: Paired spirometry data for 1993 and 1997
      were available in 47 patients without (n = 31) and with B. cepacia (n = 16)
      colonization (mean (+/- SD) ages in 1993: 12.1 years +/- 4.0 vs 12.6 years +/-
      6.5; P = 0.83). Their percentage predicted forced expiratory volume in 1 s (FEV1)
      (94.2% +/- 16.7 vs 85.9% +/- 21.2; P = 0.19) were not significantly different.
      The averaged annual fall in FEV1 over 4 years was also not significantly
      different (3.8% +/- 3.8 vs 3.6% +/- 3.7; P = 0.82). Weight percentile (Wt%),
      height percentile (Ht%) and percentage age weight for height (%WFH) were not
      significantly different between groups in 1993. By 1997, Wt% (36.7% +/- 25.1 vs
      22.3% +/- 19.6; P = 0.04) and Ht% (42.5% +/- 29.6 vs 17.6% +/- 19.4; P = 0.002)
      but not %WFH (102% +/- 10.0 vs 106% +/- 11.2; P > 0.10) were lower in subjects
      with B. cepacia. CONCLUSIONS: In adolescent CF patients, colonization with the
      Hunter strain of B. cepacia was associated with a deterioration in some
      nutritional parameters but not with an accelerated decline in FEV1 over 4 years.
      As varying pathogenicity of B. cepacia strains may account for differing rates of
      pulmonary decline, further assessment of the consequences of colonization with
      certain strains of B. cepacia in CF is needed.

PMID- 11328467
TI  - Severe chronic neutropenia in Chinese children in Hong Kong.
AB  - OBJECTIVE: Severe chronic neutropenia (SCN) is a rare and heterogeneous disorder
      in children. The epidemiology, clinical features and outcomes of SCN in Chinese
      children were reviewed. METHODOLOGY: A retrospective analysis of case records was
      undertaken for 18 children with SCN managed during a 12-year period in a
      university teaching hospital in Hong Kong. RESULTS: The median (range) age of the
      patients at initial presentation was 6.5 months (4 days-19 months). The initial
      and lowest median absolute neutrophil counts (ANC) were 0.29 x 109 /L and 0.06 x
      109 /L, respectively. Patients with congenital SCN had significantly fewer
      neutrophils in peripheral blood at diagnosis. Only five subjects received
      granulocyte colony-stimulating factor (G-CSF) treatment. All children were free
      from serious infection on follow up for 51 months. Only one child suffered from
      long-term infection-related morbidity. One patient with chronic neutropenia was
      subsequently shown to have common variable immunodeficiency. CONCLUSIONS: Most
      children with SCN in our series had favourable clinical outcomes. Our results
      support the recommendation that G-CSF should be used only in those with recurrent
      or severe infections.

PMID- 11328468
TI  - Frequency and perception of cough severity.
AB  - OBJECTIVE: The frequency of the common symptom of cough in children is unknown.
      The aim of this study was to compare cough frequency and perception of cough
      severity in children with and without recurrent cough. METHODOLOGY: Eighty-four
      children with (C) and without (NC) recurrent cough were recruited in the same
      season. Cough frequency (measured with cough-meter) and subjective cough severity
      (measured on parent-completed and child-completed diary cards on two subjective
      systems), were compared between the two groups. RESULTS: Cough frequency in C
      (median 65/day) was significantly higher than in NC (10/day). The correlation
      between daytime and night-time cough was higher in NC (rs = 0.51, P < 0.00001)
      than in C (rs = 0.3, P = 0.05). The C group had significantly higher coughs per
      score than NC, for both subjective methods. CONCLUSIONS: Children with recurrent
      cough have a higher frequency and different pattern of cough than controls
      enrolled in the same season. Subjective perception of cough severity is dependent
      on the population studied.

PMID- 11328469
TI  - Leucocyte populations in respiratory syncytial virus-induced bronchiolitis.
AB  - OBJECTIVES: To enumerate the cellular composition of the airways in infants with
      acute bronchiolitis. METHODOLOGY: Cells were obtained by airway lavage from the
      upper and lower airway and the peripheral blood of infants with respiratory
      syncytial virus (RSV)+ bronchiolitis, RSV- bronchiolitis and age-matched
      controls. RESULTS: Neutrophils are the predominant cells present in the upper and
      lower airway. Neutrophils are present at a higher number/unit volume in the
      airway than in the peripheral blood. CONCLUSIONS: Neutrophils, being the dominant
      cellular infiltrate into the airway, are likely to contribute to the
      pathophysiology of bronchiolitis. Therapies targeted at limiting neutrophil
      influx or neutrophil-mediated damage in the airway may have a therapeutic role.

PMID- 11328470
TI  - Children followed with difficulty: how do they differ?
AB  - OBJECTIVE: To determine if very low birthweight children followed with ease
      differ in any perinatal or sociodemographic characteristics, or outcomes,
      compared with children followed with more difficulty. METHODOLOGY: Consecutive
      children of birthweight < 1000 g or with gestational ages < 28 weeks born in 1991
      (n = 51) or of birthweight < 1500 g born in 1992 (n = 166) at the Royal Women's
      Hospital, Melbourne, surviving to 5 years of age, were assessed at 5 years of
      age, corrected for prematurity. Those who attended on the first mutually agreed
      appointment without substantial reluctance were considered to have been followed
      with ease. The remainder were considered to have been followed with difficulty.
      Outcomes included impairments such as cerebral palsy, blindness, deafness, and
      low IQ. Children had a disability if they had any of cerebral palsy, blindness,
      deafness requiring amplification, or an IQ more than 1 SD below the mean.
      RESULTS: Of the 217 survivors, 204 (94%) were assessed fully at 5 years of age.
      Of the 204 children assessed, 153 (75%) were followed with ease, and 51 (25%)
      with difficulty. Of data available in the perinatal period, significantly fewer
      children followed with more difficulty came from intact families, and more of
      their mothers had fewer than 12 years of schooling. More children followed with
      difficulty had a disability (41% compared with 19%), as they predominantly had
      lower IQ scores (mean difference in IQ - 12.7, 95% confidence interval - 18.0, -
      7.4). The association between difficulty of assessment and both higher rates of
      disability and lower IQ scores remained after adjustment for significant
      perinatal and sociodemographic variables. CONCLUSIONS: Children followed with
      difficulty can partly be recognized on several sociodemographic characteristics
      in the perinatal period, and have substantially worse sensorineural outcomes than
      those followed with ease. In any longitudinal study, the more incomplete the
      follow up, the lower will be the rate of adverse sensorineural outcome.

PMID- 11328471
TI  - Lactase deficiency among Malaysian children with recurrent abdominal pain.
AB  - OBJECTIVES: To determine the prevalence of lactase deficiency among Malaysian
      children with recurrent abdominal pain and to describe their clinical
      characteristics. METHODOLOGY: Twenty-four children referred consecutively to the
      University of Malaya Medical Centre who fulfilled Apley's criteria (at least
      three episodes of abdominal pain severe enough to affect normal activity over a
      period longer than 3 months) were tested for lactase deficiency using a pocket
      breath test analyser (BreatH2 meter; Europa Scientific, Cheshire, England).
      Lactulose was used to check for hydrogen-producing capacity. RESULTS: There were
      14 males and 10 females in the study, consisting of five Malays, 14 Chinese and
      five Indians. Mean age was 9.9 years. Seventeen of the 24 children (70.8%) with
      recurrent abdominal pain who underwent the breath hydrogen test had a positive
      result. In those with a negative result, subsequent lactulose administration
      resulted in a positive rise in breath hydrogen. None of the 24 children developed
      abdominal pain during the test. All the Indian subjects, 71.4% of the Chinese
      subjects and 40% of the Malay subjects with recurrent abdominal pain had lactase
      deficiency. The proportion of boys and girls with lactase deficiency was similar
      (71.4 vs 70.0%, respectively). There was no significant difference between
      lactase sufficient and deficient children with recurrent abdominal pain with
      regard to sex, age, ethnic group and clinical features. Following a lactose-free
      diet, none of the children in the breath hydrogen positive and negative groups
      reported any appreciable difference in pain symptoms. CONCLUSIONS: The prevalence
      of lactase deficiency among this group of Malaysian children with recurrent
      abdominal pain was high, but lactase deficiency did not appear to play an
      important role in causing the symptoms.

PMID- 11328472
TI  - Nasal continuous positive airway pressure and outcomes of preterm infants.
AB  - OBJECTIVES: To document the effects of changing to a primarily nasal continuous
      positive airway pressure (CPAP)-based system of respiratory support on
      respiratory and non-respiratory outcomes in preterm infants. METHODOLOGY:
      Outcomes in two groups of preterm infants with a birthweight of 1000-1499 g were
      compared retrospectively over a 5-year period before (period I; n = 57) and after
      (period II; n = 59) the introduction of a primarily nasal CPAP-based approach to
      respiratory support, modelled closely on that used at the New York Presbyterian
      Hospital (Columbia University), formally known as the Columbia-Presbyterian
      Medical Center, in New York. RESULTS: From period I to period II, there was a
      decline in the number of infants ventilated (65 vs 14%, respectively) and
      receiving surfactant (40 vs 12%, respectively) and in the median days of
      ventilation (6 vs 2, respectively) and oxygen (4 vs 2, respectively). There were
      decreases in chronic lung disease (CLD) at 28 days (11 vs 0%, respectively),
      death or CLD at 28 days (16 vs 3%, respectively), the use of pressor support (34
      vs 7%, respectively), the incidence of necrotizing enterocolitis (11 vs 0%,
      respectively), time to reach full oral feeds (17.3 vs 13.2 days, respectively),
      discharge weight (2569 vs 2314 g, respectively) and average length of stay (61 vs
      52.9 days, respectively). There were no differences in neurosonographic or other
      morbidity outcomes. CONCLUSIONS: A CPAP-based approach to respiratory support of
      the preterm infant may decrease the invasiveness and duration of respiratory
      support and may decrease respiratory and some non-respiratory adverse outcomes
      without an associated increase in neurosonographic or other morbidity outcomes.
      Further prospective trials are warranted.

PMID- 11328473
TI  - Perforation complications of percutaneous central venous catheters in very low
      birthweight infants.
AB  - OBJECTIVE: To prospectively survey perforation complications of consecutively
      inserted percutaneous central venous catheters (PCVC) in very low birthweight
      (VLBW) infants over a 2 year period. METHODOLOGY AND RESULTS: Three serious
      perforation complications were encountered in a series of 100 consecutive PCVC.
      One infant (birthweight 685 g) developed pericardial effusion and fatal cardiac
      tamponade during the use of a polyurethane PCVC. At autopsy, the pericardial sac
      contained 8 mL fluid with a glucose concentration of 109 mmol/L and the catheter
      tip was embedded in the right ventricular wall. The second infant (birthweight
      1380 g) showed pleural effusion and transient immobility of the right
      diaphragmatic leaf after perforation of a similar PCVC into the right pleural
      cavity. The third perforation, causing subcutaneous oedema, occurred in a 655 g
      infant who had a silastic PCVC. CONCLUSIONS: The data suggest a 3% incidence for
      PCVC-associated symptomatic perforation complications and a 1% incidence for
      fatal perforations, despite a policy of careful placement. The data also indicate
      that perforation complications occur regardless of the size or material of the
      PCVC. Proper visualization of the PCVC and vigilant attention to its location is
      required to prevent these rare but potentially fatal complications.

PMID- 11328474
TI  - Acquired central diabetes insipidus in children: a 12-year Brisbane experience.
AB  - OBJECTIVE: To study the clinical, endocrine and radiological features and
      progress of children presenting with acquired diabetes insipidus (CDI).
      METHODOLOGY: Chart review of children presenting because of CDI to Brisbane
      paediatric endocrine clinics between 1987 and 1999. RESULTS: Thirty-nine children
      (female/male ratio 21/18) aged 0.1-15.4 years (mean age 6.7 years) were
      identified. Aetiologies were head trauma or familial in eight cases (20.5%) each,
      central nervous system (CNS) tumours in five cases (12.8%), CNS malformations in
      four cases (10.2%), histiocytosis in three cases (7%) and hypoxia and infection
      in two cases (5.1%) each. Seven cases (17.9%) remain undiagnosed. Of the 32 (82%)
      cases with isolated anti-diuretic hormone deficiency at presentation, 24 cases
      (61.5%) experienced no further endocrine deficit. Additional endocrine deficits
      occurred mainly in the tumour or undiagnosed groups. On follow-up brain magnetic
      resonance imaging (MRI) scans in the seven undiagnosed cases, six patients had
      mild or no change and one patient had marked improvement of MRI findings. These
      changes occurred 10-48 months (mean 18 months) after presentation. CONCLUSIONS:
      Children without an aetiological diagnosis for the uncommon condition of acquired
      CDI require careful follow-up. More intensive investigation at presentation (e.g.
      estimation of cerebrospinal fluid human chorionic gonadotrophin) promises to
      lessen the number of such cases. Pituitary stalk biopsies should be reserved for
      those patients with progressive MRI changes. If these changes do not occur early,
      our experience suggests that follow-up MRI scans may need to be performed only
      yearly.

PMID- 11328475
TI  - Review of the outcome of management of Graves' disease in children and
      adolescents.
AB  - OBJECTIVE: To review our recent experience in the management of paediatric
      Graves' disease, the leading cause of hyperthyroidism in childhood, in view of
      ongoing international debate regarding therapy. METHODOLOGY: Retrospective
      medical record review of patients with Graves' disease, treated between 1985 and
      1999, at the Royal Children's Hospital, Melbourne. RESULTS: Forty patients, aged
      at diagnosis between 2.9 and 17.6 years (median age 11 years; 31 females), were
      treated. Thirty-three patients received either definitive therapy or at least 24
      months medical therapy and follow up at the time of the study. Six patients
      experienced successful remission upon withdrawal of medication (median medication
      duration 3.2 years; four females; median follow up 4.1 years). Children
      successfully achieving remission were younger at presentation than those
      requiring surgery (9.5 vs 12.9 years, respectively; P = 0.01). Ten patients were
      treated surgically, leaving 4-6 g residual thyroid tissue. Surgical indications
      included failed initial medical therapy, relapse after medication cessation, non
      compliance and significant medication side effects. During a median follow up of
      1.7 years (range 0.2-5 years), three of 10 patients have subsequently relapsed
      and four of 10 patients are receiving postoperative thyroxine replacement.
      Transient hypocalcaemia occurred in five patients and temporary recurrent
      laryngeal nerve palsy occurred in two patients. CONCLUSIONS: Fewer than 20% of
      children experienced successful sustained remission at median follow up of 3.2
      years. Medication remains a well-tolerated therapeutic option. Surgery is a
      reasonable alternative when there are specific indications. In order to decrease
      the likelihood of surgical relapse, less than 4 g thyroid tissue should be left
      postoperatively.

PMID- 11328476
TI  - Cerebral palsy in Victoria, Australia: mortality and causes of death.
AB  - OBJECTIVE: To study the causes of death and the characteristics of children with
      cerebral palsy that had died over a 25-year period in Victoria, Australia.
      METHODOLOGY: Names of children that had died were collected from the Victorian
      Cerebral Palsy Register. Their hospital records were studied and information was
      gathered about age of death, motor impairment, the presence or absence of
      associated disabilities and cause of death. RESULTS: One hundred and fifty-five
      children had died during the period 1970-95. The majority of children had severe
      spastic quadriplegia, intellectual disability and epilepsy. The predominant cause
      of death was pneumonia, although for many children who died at home the cause was
      unknown. CONCLUSIONS: Children with cerebral palsy are a diverse group and those
      with a severe motor deficit have a reduced life expectancy. Lung disease remains
      an important cause of morbidity and mortality for this group. Further information
      about the causes of death is needed, particularly for those children that die at
      home.

PMID- 11328477
TI  - Congenital and perinatal infections with cytomegalovirus.
AB  - Congenital cytomegalovirus (CMV) infections remain the leading viral cause of
      congenital malformations in the developed world. Despite advances in our
      knowledge, the epidemiology and natural history of congenital CMV infection are
      still poorly understood, particularly in Australia. Congenital CMV causes illness
      ranging from no clinical disease (asymptomatic, but infected) through to
      prematurity, encephalitis, deafness and haematological disorders and death.
      Perinatal CMV acquisition usually results in less severe illness including
      asymptomatic infection, acute infection with hepatitis, fever, and pneumonitis.
      CMV infects only humans, and in vitro and in vivo models for intrauterine
      infection are required in order to test new treatments, and better describe the
      pathogenesis of congenital CMV. Using new knowledge of the epidemiology and
      natural history of CMV, treatment regimens during late pregnancy are currently
      undergoing clinical trial although no definitive recommendations are available.

PMID- 11328478
TI  - Facial paralysis in childhood hypertension.

PMID- 11328479
TI  - Pitfalls of gastric intubation in premature infants.
AB  - Gastric intubation, by oral or nasal route is an essential procedure in the
      management of premature infants, for gastric aspiration and for feeding.
      Oesophageal perforation is a rare but important complication of this commonly
      performed procedure. An illustrative case is presented. Difficulty passing a tube
      into the stomach is the first clue to the diagnosis. Understanding the evolution
      of clinical signs and recognizing the radiological changes facilitates an early
      diagnosis, thereby enabling successful non-operative management.

PMID- 11328480
TI  - Partial monosomy 10q with partial trisomy 11q due to paternal balanced
      translocation.
AB  - A male neonate with partial monosomy 10q and partial trisomy 11q, due to paternal
      balanced translocation, and who had cerebellar and olfactory lobe hypoplasia,
      cardiovascular defects, duodenal atresia and imperforate anus, is presented. To
      the best of our knowledge, this is the first report on this combination of
      chromosomal abnormalities.

PMID- 11328481
TI  - Car window entrapment and accidental childhood asphyxia.
AB  - A 3-year-old boy was found hanging from a partly opened car window. Attempted
      resuscitation was unsuccessful. Postmortem reconstruction of events leading up to
      death indicated that the boy had slipped while standing on his tricycle and
      entrapped his head as he was attempting either to look into the car, or to climb
      in through the window. While it is not always possible to completely secure
      childhood environments, open cars should not be regarded as safe places for young
      children to play in or around when an adult is not in attendance. To minimize the
      chance of injury or death to children from parked cars, young children should be
      removed from vehicles and all windows and doors securely closed and locked, if
      they are to be left in the vicinity of the car to play unsupervised.

PMID- 11328482
TI  - Neonatal neuroblastoma presenting with respiratory distress.
AB  - A male infant presenting with respiratory distress was found to have primary
      thoracic neuroblastoma. This method of presentation in the newborn period is
      rare. His symptoms resolved spontaneously with conservative management. Full
      staging revealed a poorly differentiated stage 2 tumour with favourable
      cytogenetic markers.

PMID- 11328483
TI  - Rotavirus encephalopathy: pathogenesis reviewed.
AB  - Two cases of rotavirus gastroenteritis associated with neurological involvement,
      one with encephalitis (defined by abnormal neurological signs, cerebrospinal
      fluid (CSF) pleocytosis and detection of rotavirus genomic nucleic acid in the
      CSF) and one with a non-inflammatory encephalopathy (defined by abnormal
      neurological signs, an entirely normal CSF and detection of rotavirus genomic
      nucleic acid in the CSF), are presented and used as a basis to review and explore
      potential pathogenetic mechanisms, including direct viral replication within
      neurons and indirect effects of the newly described rotavirus 'enterotoxin'.

PMID- 11328484
TI  - Synthesis, biology, NMR and conformation studies of the topographically
      constrained delta-opioid selective peptide analogs of [beta-iPrPhe(3)]deltorphin
      I.
AB  - Replacement of Phe3 in the endogenous delta-opioid selective peptide deltorphin I
      with four optically pure stereoisomers of the topographically constrained, highly
      hydrophobic novel amino acid beta-isopropylphenylalanine (beta-iPrPhe) produced
      four pharmacologically different deltorphin I peptidomimetics. Radiolabeled
      ligand-binding assays and in vitro biological evaluation indicate that the
      stereoconfiguration of the iPrPhe residue plays a crucial role in determining the
      binding affinity, bioactivity and selectivity of [beta-iPrPhe3]deltorphin I
      analogs: a (2S,3R) configuration of the iPrPhe3 residue in [beta
      iPrPhe3]deltorphin I provided the most desirable biological properties with
      binding affinity (IC50 = 2 nM), bioassay potency (IC50 = 1.23 nM in MVD assay)
      and exceptional selectivity for the delta-opioid receptor over the mu-opioid
      receptor (30 000). Further conformational studies based on two-dimensional NMR
      and computer-assisted molecular modeling suggested a model for the possible
      bioactive conformation in which the Tyr1 and (2S,3R)-beta-iPrPhe3 residues adopt
      trans side-chain conformations, and the linear peptide backbone favors a
      distorted beta-turn conformation.

PMID- 11328485
TI  - Facile synthesis of orthogonally protected amino acid building blocks for
      combinatorial N-backbone cyclic peptide chemistry.
AB  - Protected Nalpha-(aminoallyloxycarbonyl) and Nalpha-(carboxyallyl) derivatives of
      all natural amino acids (except proline), and their chiral inverters, were
      synthesized using facile and efficient methods and were then used in the
      synthesis of Nalpha-backbone cyclic peptides. Synthetic pathways for the
      preparation of the amino acid building units included alkylation, reductive
      amination and Michael addition using alkylhalides, aldehydes and alpha,beta
      unsaturated carbonyl compounds, and the corresponding amino acids. The resulting
      amino acid prounits were then subjected to Fmoc protection affording optically
      pure amino acid building units. The appropriate synthetic pathway for each amino
      acid was chosen according to the nature of the side-chain, resulting in fully
      orthogonal trifunctional building units for the solid-phase peptide synthesis of
      small cyclic analogs of peptide loops (SCAPELs). Nalpha-amino groups of building
      units were protected by Fmoc, functional side-chains were protected by t
      Bu/Boc/Trt and N-alkylamino or N-alkylcarboxyl were protected by Alloc or Allyl,
      respectively. This facile method allows easy production of a large variety of
      amino acid building units in a short time, and is successfully employed in
      combinatorial chemistry as well as in large-scale solid-phase peptide synthesis.
      These building units have significant advantage in the synthesis of peptido
      related drugs.

PMID- 11328486
TI  - Analysis of gammabeta, betagamma, gammagamma, betabeta continuous turns in
      proteins.
AB  - We report the observation of continuous turns in proteins which comprise
      individual gamma-turns or beta-turns or both that are situated immediately one
      after the other along the polypeptide chain. The continuous turns were identified
      from a representative data set of three-dimensional protein crystal structures.
      The gammabeta/betagamma, gammagamma and betabeta continuous turns represent
      peptides of varying amino acid residue lengths and conformations. The continuous
      turns frequently observed in proteins were: gammabeta, between a coil and a
      strand; betagamma, between a helix and a strand; gammagamma, between coils; and
      betabeta, either between a strand and a coil or between strands or coils. We
      determined the statistically significant amino acid residue preferences at
      individual positions in the turn, calculated amino acid positional potentials and
      analyzed main chain hydrogen bonds and side-chain interactions likely to
      stabilize the continuous turns. The data on continuous turns have been integrated
      in the database of structural motifs in proteins (DSMP) on our web server at
      (http://www.cdfd.org.in/dsmp.html). This is useful to make queries on sequences
      compatible with different continuous turns.

PMID- 11328487
TI  - Artificial ion channels formed by a synthetic cyclic peptide.
AB  - A new cyclic peptide 1 having an (LLLD)3 configuration pattern was designed that
      is capable of forming artificial transmembrane ion channels by self-assembly of
      planar peptide rings, with hydrophilic groups arrayed in the interior of the
      channel. Ion permeability in the presence of the synthetic peptide 1, cyclo[-Trp
      Dap-Leu-D-Ala-Trp-Ser-Val-D-Ala-Trp-Ser-Ile-Gly-] (Dap: L-diaminopropionic acid),
      was observed in lipid bilayer membranes. The pH dependence of ionic conductance
      showed that the beta-amino group of Dap may play a role in the conductance of the
      peptide channels. Fourier-transform infrared and circular dichroism data imply
      that, in a membrane, a stack of cyclic peptides is formed in which the inter
      peptide H bonds form a kind of beta-structure analogous to that in the gramicidin
      A dimer and distinct from the H-bonding pattern of the beta-barrels.

PMID- 11328488
TI  - Ac10c: a medium-ring, cycloaliphatic Calpha,alpha-disubstituted glycine.
      Incorporation into model peptides and preferred conformation.
AB  - Two complete series of N-protected oligopeptide esters to the pentamer level from
      1-amino-cyclodecane-1-carboxylic acid (Ac10c), an alpha-amino acid
      conformationally constrained through a medium-ring Calphai <--> Calphai
      cyclization, and either the L-Ala or Aib residue, along with the N-protected
      Ac10c monomer and homo-dimer alkylamides, were synthesized using solution methods
      and fully characterized. The preferred conformation of these model peptides was
      assessed in deuterochloroform solution using FT-IR absorption and 1H NMR
      techniques. Furthermore, the molecular structures of two derivatives (Z-Ac10c-OH
      and Fmoc-Ac10c-OH) and two peptides (the dipeptide ester Z-Ac10c-L-Phe-OMe and
      the tripeptide ester Z-Aib-Ac10c-Aib-OtBu) were determined in the crystal state
      using X-ray diffraction. The experimental results support the view that beta
      bends and 3(10)-helices are preferentially adopted by peptides rich in Ac10c, the
      third largest cycloaliphatic C(alpha,alpha)-disubstituted glycine known. This
      investigation allowed us to complete a detailed conformational analysis of the
      whole 1-amino-cycloalkane-1-carboxylic acid (Ac(n)c, with n = 3-12) series, which
      represents the prerequisite for our recent proposal of the 'Ac(n)c scan' concept.

PMID- 11328489
TI  - Transport characteristics of peptides and peptidomimetics: I. N-methylated
      peptides as substrates for the oligopeptide transporter and P-glycoprotein in the
      intestinal mucosa.
AB  - Peptides and peptidomimetics often exhibit poor oral bioavailability due to their
      metabolic instability and low permeation across the intestinal mucosa. N
      Methylation has been used successfully in peptide-based drug design in an attempt
      to improve the metabolic stability of a peptide-based lead compound. However, the
      effect of N-methylation on the absorption of peptides through the intestinal
      mucosa is not well understood, particularly when transporters, i.e. the
      oligopeptide transporter (OPT) and P-glycoprotein (P-gp), modulate the passive
      diffusion of these types of molecules. To examine this, terminally free and
      terminally modified (N-acetylated and C-amidated) analogs of H-Ala-Phe-Ala-OH
      with N-methyl groups on either the Ala-Phe or Phe-Ala peptide bond were
      synthesized. Transport studies using Caco-2 cell monolayers, an in vitro model of
      the intestinal mucosa, showed that N-methylation of the Ala-Phe peptide bond of H
      Ala-Phe-Ala-OH stabilized the molecule to protease degradation, and the resulting
      analog exhibited significant substrate activity for OPT. However, N-methylation
      of the Phe-Ala peptide bond of H-Ala-Phe-Ala-OH did not stabilize the molecule to
      protease degradation, and the substrate activity of the resulting molecule for
      OPT could not be determined. Interestingly, N-methylation of the Phe-Ala peptide
      bond of the terminally modified tripeptide Ac-Ala-Phe-Ala-NH2 decreased the
      substrate activity of the molecule for the efflux transporter P-gp. In contrast,
      N-methylation of the Ala-Phe peptide bond of the terminally modified tripeptide
      Ac-Ala-Phe-Ala-NH2 increased the substrate activity of the molecule for P-gp.

PMID- 11328490
TI  - Hypogin, a novel antifungal peptide from peanuts with sequence similarity to
      peanut allergen.
AB  - A protein designated hypogin, with a prominent suppressive action on the growth
      of the fungi Mycosphaerella arachidicola, Fusarium oxysporum and Coprinus
      comatus, was isolated from seeds of the peanut Arachis hypogaea. The protein
      inhibited human immunodeficiency virus (HIV) reverse transcriptase and enzymes
      associated with HIV infection including alpha-glucosidase and beta-glucosidase.
      The proliferative response of mouse splenocytes was attenuated in the presence of
      the protein. The protein exhibited a molecular mass of 7.2 kDa in tricine gel
      electrophoresis and gel filtration on Superdex 75 and an N-terminal sequence
      resembling peanut allergen Ara H1. The isolation procedure involved affinity
      chromatography on Affi-gel blue gel and ion-exchange chromatography on CM
      Sepharose. The protein was adsorbed in both chromatographic media.

PMID- 11328492
TI  - Screening of some plants from Northern Argentina for their antimicrobial
      activity.
AB  - AIMS: Screening of antimicrobial activity in 25 plant species from Northern
      Argentina. METHODS AND RESULTS: Inhibition of microbial growth was measured by a
      microplate assay with an oxidation-reduction indicator (Alamar Blue). Test
      organisms were: Escherichia coli, Salmonella typhimurium, Pseudomonas aeruginosa,
      Klebsiella pneumoniae, Staphylococcus aureus and Enterococcus faecium. Weak
      inhibitory activities (MIC=0.5 mg dry matter ml(-1)) were found in methanolic
      extracts of Rivina humilis, Crateva tapia, Funastrum claucum and Schinopsis
      balansae. Stronger bacteriostatic power was detected in Vassobia breviflora
      (MIC=0.25 mg ml(-1) against Staphylococcus aureus, and 0.5 mg ml(-1) against
      Enterococcus faecium). This activity was purified five-fold by extraction with
      dichloromethane, and it was found equally effective against susceptible or
      antibiotic-resistant strains of Staph. aureus. In addition, the purified extract
      was synergistic with gentamicin, and it was bactericidal at 24 h, with a
      concentration of 0.25 mg ml(-1). CONCLUSION: There is a significant antimicrobial
      activity in Vassobia breviflora. SIGNIFICANCE AND IMPACT OF THE STUDY: Further
      studies will be required to disclose the potential importance of these findings.

PMID- 11328491
TI  - Probing opioid receptor-ligand interactions by employment of indolizidin-9-one
      amino acid as a constrained Gly(2)-Gly(3) surrogate in a leucine-enkephalin
      mimic.
AB  - The relationship between the conformation and biological activity of Leu
      enkephalin was studied using (2S,6R,8S)-9-oxo-8-N-(Boc)amino-1
      azabicyclo[4.3.0]nonane-2-carboxylic acid [(2S,6R,8S)-1, I(9)AA] as a constrained
      Gly(2)-Gly(3) dipeptide surrogate. [I(9)AA](2,3)-Leu-enkephalin 12 was assembled
      using solid-phase peptide synthesis on Merrifield resin with TBTU as the coupling
      reagent. The in vitro assays indicated that [I(9)AA](2,3)-Leu-enkephalin 12
      exhibited affinities for the mu- and delta-opioid receptors that were three
      orders of magnitude lower than that of Leu-enkephalin, as well as partial agonist
      character for both receptors. In in vivo assays for spinal analgesia, the
      indolizidinone analog 12 showed significantly enhanced duration of action,
      indicating an increased metabolic stability. Conformational analysis was
      performed using NMR and CD spectroscopy. The amide temperature coefficients and
      3J(NH-CalphaH) coupling constants for 12 could not support a hydrogen-bonded beta
      turn structure; however, its CD spectrum indicated a turn conformation.
      Incorporation of indolizidinone amino acid 1 into Leu-enkephalin thus provided
      additional support for the importance of a turn conformation for the biological
      activity of the native peptide.

PMID- 11328493
TI  - Evaluation of recovery methods to detect faecal streptococci in polluted waters.
AB  - AIMS: This paper compares the faecal streptococci count on 25 samples of polluted
      waters obtained with three techniques: most probable number (MPN), membrane
      filtration (MF) and pour plate (PP) methods. Although the PP method is a simple
      technique, familiar to water bacteriologists, it is not recommended in the
      international methods. METHODS AND RESULTS: For the MPN method, azide dextrose
      broth and ethyl violet azide broth were employed. For the MF technique, Millipore
      filters were placed onto azide maltose agar (KF agar), while for the PP method, 1
      ml of a decimal water dilution was added to (Kennel Faecal) KF medium. Regression
      analysis and Friedman's ANOVA were performed to determine the relationship
      between faecal streptococci counts obtained with the three techniques.
      Statistical analysis of the results showed that the MPN, MF and PP techniques
      were equally valid with respect to faecal streptococci enumeration in polluted
      waters. CONCLUSION: Since the PP method was found to be as good as the other
      techniques, it may be preferred in polluted waters. It is more economical in
      terms of both time and materials than the MPN count, and it is as accurate as the
      MF count. SIGNIFICANCE AND IMPACT OF THE STUDY: This study indicates that the PP
      method, although not recommended internationally, is a reliable alternative to MF
      and MPN.

PMID- 11328494
TI  - Comparative study of the influence of melatonin and vitamin E on the surface
      characteristics of Escherichia coli.
AB  - AIMS: Melatonin is a hormone produced by the pineal gland and that affects the
      response of various cell membranes to an oxidative stimulus. METHODS AND RESULTS:
      The present study evaluates the hydrophobic characteristics of Escherichia coli
      in response to melatonin (100 nmol l(-1), 200 micromol l(-1)) and to vitamin E (5
      mg dl(-1)). A reduction was found in the surface hydrophobicity of E. coli at
      concentrations of 200 micromol l(-1) melatonin in a Mueller-Hinton (MH) broth.
      These effects were modified when a protein synthesis inhibitor (chloramphenicol)
      was added at sub-lethal concentrations to the broth. Vitamin E produced a greater
      diminution in surface hydrophobicity than melatonin. The adherence of E. coli to
      nitrocellulose filters increased in the presence of melatonin + chloramphenicol,
      and vitamin E. The effects observed were independent of the concentration of iron
      in the broth. CONCLUSION: Oxidative stress plays an important role in modifying
      the surface characteristics of E. coli, which could affect the micro-organism's
      capacity to adhere to epithelia. SIGNIFICANCE AND IMPACT OF THE STUDY: We think
      that the oxide reduction potential of the host may be a determinant factor in the
      bacterial colonization of animal tissue.

PMID- 11328495
TI  - Pre-slaughter handling of cattle and Shiga toxin-producing Escherichia coli
      (STEC).
AB  - AIMS: The aim of the study was to monitor the shedding and transmission of
      generic and Shiga toxin-producing Escherichia coli (STEC) in a consignment of
      cattle during lot feeding. METHODS AND RESULTS: Faecal and environmental samples
      were tested for total E. coli and screened with PCR specific for Shiga toxin and
      O157 rfb. STEC were isolated using colony hybridization and characterized by
      serology and genotyping. STEC prevalence initially decreased after the diet shift
      from pasture to grain, although there were intermittent peaks in numbers of
      cattle shedding STEC and E. coli O157. Water troughs and soil were intermittently
      contaminated. Common genotypes and serotypes were isolated from animals, water
      and soil in the feedlot, with additional types introduced at slaughter.
      CONCLUSION: STEC and E. coli O157 are endemic in cattle and intermittent peaks in
      shedding occur. Prevention of these peaks and/or reduction in transmission is
      required to reduce the risk of carcass contamination during slaughter.
      SIGNIFICANCE AND IMPACT OF THE STUDY: These findings contribute to the
      understanding of the ecology of STEC and suggest control points for reducing STEC
      contamination in feedlot cattle production.

PMID- 11328496
TI  - Sodium chloride enhances recovery and growth of acid-stressed E. coli O157:H7.
AB  - AIMS: Combinations of sodium chloride and acid are frequently used to inhibit
      growth of spoilage and pathogenic bacteria in food. The influence of differing
      sodium chloride, lactate and pH values on the growth of stressed and unstressed
      cells of a non-toxigenic strain of Escherichia coli O157:H7 was studied. METHODS
      AND RESULTS: At pH 5.5 or 6.0, there was little or no effect on the growth rate
      in the presence of lactate and/or sodium chloride, but the lag times were longer
      as the lactate concentration increased. At pH 5.0, in the absence of sodium
      chloride, increasing the lactate concentration increased the growth rate and the
      lag time; no growth occurred in the presence of 1.5 g 100 g(-1) lactate. In the
      presence of 4-6 g 100 g(-1) sodium chloride, growth occurred at 1.5 g 100 g(-1)
      lactate. The growth rate was similar at all lactate concentrations. CONCLUSION:
      The results demonstrate that the presence of sodium chloride promoted growth of
      E. coli O157:H7, especially under stressful conditions of low pH. SIGNIFICANCE
      AND IMPACT OF THE STUDY: These findings could have implications for the use of
      acid and sodium chloride as a preservation treatment for the inhibition of E.
      coli O157:H7 in food.

PMID- 11328497
TI  - Methods for the isolation of water-borne Escherichia coli O157.
AB  - AIMS: To develop improved methods for the detection of Escherichia coli O157 from
      water and sediments. METHODS AND RESULTS: The effects of different broth
      enrichment media (unsupplemented tryptic soya broth, tryptic soya broth with
      antibiotics, and gram-negative broth), incubation durations (5 and 24 hrs),
      incubation temperatures (37 and 44.5 degrees C) and the use of immunomagnetic
      separation (IMS) on the sensitivity of E. coli O157 detection were evaluated on
      artificially and naturally-contaminated water and sediment samples. The
      sensitivity of recovery of E. coli O157 from samples was dependent upon the media
      composition, temperature duration of incubation and the use of IMS. CONCLUSION:
      Use of high temperature (44.5 degrees C) incubation for 24 hrs in unsupplemented
      tryptic soya broth and the use of IMS improved the sensitivity of E. coli O157
      culture from water and sediment samples. SIGNIFICANCE AND IMPACT OF THE STUDY:
      The methods described can be used to increase the sensitivity of E. coli O157
      detection from water and sediments.

PMID- 11328498
TI  - Detection of Clostridium botulinum neurotoxin type A using immuno-PCR.
AB  - AIMS: An immuno-polymerase chain reaction (immuno-PCR) has been developed for the
      sensitive detection of antigens, which greatly extends the detection limits of
      immunoassays. In the current study, the method was applied to the detection of
      Clostridium botulinum neurotoxin type A (BTx-A). METHODS AND RESULTS: Anti-BTx-A
      antibody-DNA conjugates were synthesized using a heterobifunctional cross-linker
      reagent to covalently link the reporter DNA and the antibodies. The antibody-DNA
      conjugates with antigens were amplified by PCR, and dose-dependent relationships
      for each analyte were demonstrated. Detection limits of immuno-PCR for BTx-A
      (3.33 x 10(-17) mol) exceeded the conventional enzyme-linked immunosorbent assay
      (3.33 x 10(-14) mol) by a 1000-fold enhancement in detection sensitivity.
      CONCLUSION: Detection of BTx-A antigens by immuno-PCR demonstrated 100%
      sensitivity and 100% specificity in 100-fold magnitude below the detection limit
      of ELISA. SIGNIFICANCE AND IMPACT OF THE STUDY: It is concluded that the immuno
      PCR method could be used to detect a very low level of BTx-A for clinical
      diagnosis.

PMID- 11328499
TI  - Rapid, high-throughput extraction of bacterial genomic DNA from selective
      enrichment culture media.
AB  - AIMS: To create a fast, sensitive and inexpensive high-throughput method for the
      extraction of bacterial genomic DNA from selective-enrichment culture media.
      METHODS AND RESULTS: Lysis of bacteria was achieved using guanidinium
      isothiocyanate, and DNA was extracted using 96-well glass microfibre filtration
      plates. Extraction-PCR detected the presence of 1 cfu Yersinia ruckeri and 16 cfu
      Lactococcus garvieae 200 microl(-1) sample of selective-enrichment medium.
      CONCLUSION: An efficient method for high-throughput extraction of bacterial
      genomic DNA from selective-enrichment culture media was achieved. SIGNIFICANCE
      AND IMPACT OF THE STUDY: This method enables detection of covert bacterial
      infections in fish. The simultaneous extraction of large numbers of samples
      allows for its use in bacterial monitoring programmes and quarantine.

PMID- 11328500
TI  - Kinetic differences of purified laccases from six Pleurotus ostreatus strains.
AB  - AIMS: Enzyme kinetics of purified laccases from six different Pleurotus ostreatus
      strains were determined in the oxidation of syringaldazine, guaiacol and ABTS.
      METHODS AND RESULTS: Significant differences in the kinetic constants were found.
      Catalytic activity (kcat) ranged from 19 to 941 U mg(-1) for syringaldazine, from
      18 to 1565 U mg(-1) for ABTS, and from 4 to 44 U mg(-1) for guaiacol. The
      apparent affinity constants (KM) also showed significant differences between the
      different strains, from 12 to 52 micromol l(-1) for syringaldazine, from 8 to 79
      micromol l(-1) for ABTS, and from 0.46 to 6.61 mmol l(-1) for guaiacol. No
      differences were found either on the effect of increasing concentrations of
      organic solvent (acetonitrile) or on the activity pH profile. The temperature
      profile was the same for all the P. ostreatus strains, except for the IE8 strain,
      which seems to be more sensitive to temperature. The kinetic and stability data
      from the six P. ostreatus strains were also compared with those obtained from
      other white rot fungi, Coriolopsis gallica and Trametes versicolor, showing clear
      differences. CONCLUSION: The different P. ostreatus isolates showed different
      kinetic constants. SIGNIFICANCE AND IMPACT OF THE STUDY: The different enzymatic
      properties of laccases from various P. ostreatus strains should be considered for
      a potential industrial or environmental application.

PMID- 11328501
TI  - Comparison of sludge and clinical isolates of Listeria monocytogenes.
AB  - AIMS: Listeria monocytogenes strains isolated in the same geographical area from
      sewage sludge and from patients presenting with listeriosis were compared.
      METHODS AND RESULTS: All isolates were typed by serotyping, phage typing and
      SmaI/ApaI pulsed-field gel electrophoresis (PFGE). Among the sludge isolates
      (n=32), 22 subtypes could be distinguished by the combination of all typing
      methods. The human isolates (n=11) were distributed into 10 subtypes which
      clearly differed from those observed among sludge isolates, except for one
      cluster formed by two related human isolates which showed high similarity in PFGE
      patterns (SmaI: 92%; ApaI: 89.5%) with one sludge isolate. CONCLUSION: These
      results suggest the existence of an epidemiological link between sludge and human
      isolates, but they may also be reflecting the distribution of L. monocytogenes
      types within the environment. SIGNIFICANCE AND IMPACT OF THE STUDY: Sludge and
      human L. monocytogenes may be related but further epidemiological studies are
      necessary to elucidate this point.

PMID- 11328502
TI  - Application of resazurin for estimating abundance of contaminant-degrading micro
      organisms.
AB  - AIMS: The aim of the current study was to test whether resazurin changed colour
      when incubated with a range of organic chemicals used as growth substrates in
      bioremediation studies and to determine whether resazurin was more effective in
      estimating microbial growth than turbidity alone (i.e. no resazurin) or use of
      the dye, methylene blue. METHODS AND RESULTS: Resazurin was incubated with a
      range of organic chemicals that were used as substrates in an MPN assay. Only 1,2
      dichlorobenzene, 2,4-D, glycol sulphite and sulphinol reacted to generate false
      positives. Resazurin was also used to estimate micro-organisms in a series of
      bioremediation studies. CONCLUSION: The results showed that resazurin was more
      sensitive than methylene blue or turbidity alone as an indicator of microbial
      growth. SIGNIFICANCE AND IMPACT OF THE STUDY: The significance of the current
      study is that resazurin should be used in MPN assays for estimating contaminant
      degrading micro-organisms instead of turbidity alone or other dyes such as
      methylene blue.

PMID- 11328503
TI  - The potential biocontrol agent Pseudomonas antimicrobica inhibits germination of
      conidia and outgrowth of Botrytis cinerea.
AB  - AIMS: Antifungal metabolites of Pseudomonas antimicrobica have previously been
      shown to inhibit conidial germination of the grey mould pathogen Botrytis
      cinerea. In this study, metabolites of the bacterium have been tested at
      different stages of Botrytis germination to determine their effects on germ tube
      production and extension. METHODS AND RESULTS: Metabolites were added to conidia
      that had been pre-incubated for either 120 or 255 min. Pseudomonas antimicrobica
      inhibited B. cinerea conidial germination and caused a significant reduction in
      germ tube extension, irrespective of the stage of germination. Abnormal
      germination and a reduction in the frequency of lateral branching of the germ
      tubes in the presence of the metabolites were also reported, suggesting
      interference with normal hyphal development. CONCLUSION: The bacterium can
      inhibit germination of conidia and extension of germ tubes at different stages of
      Botrytis development. SIGNIFICANCE AND IMPACT OF THE STUDY: The antagonistic
      activity of the bacterium has promising implications for its use as a biocontrol
      agent.

PMID- 11328504
TI  - Production of ultrasensitive antibodies against aflatoxin B1.
AB  - AIMS: To produce specific antibodies against the haptenic fungal toxin aflatoxin
      B1 (AFB1) and apply these antibodies in immunochemical assays for aflatoxins.
      METHODS AND RESULTS: Rabbits were immunized using an AFB1-bovine serum albumin
      conjugate and serum titres determined by double-antibody enzyme immunoassay. High
      titres of antibodies with very high affinity for AFB1 were obtained 15 and 4
      weeks after the initial immunization and the first booster immunization
      respectively. The antibodies were employed in enzyme immunoassay (EIA) and
      immunoaffinity chromatography (IAC) methods for aflatoxins. With a detection
      limit of 15.8 pg ml(-1) for AFB1, the EIA employing these antibodies is the most
      sensitive test for AFB1 described so far. In IAC columns, these antibodies
      provided high binding capacity for all major aflatoxins, including AFB1, AFB2,
      AFG1 and AFG2. CONCLUSION: The antibodies described here are useful for the
      analysis of trace levels of aflatoxins. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Polyclonal antibody-based EIA and IAC methods for aflatoxin analysis offer a
      suitable alternative to the more expensive monoclonal antibody-based methods.

PMID- 11328505
TI  - Differentiation of Lactobacillus delbrueckii subsp. bulgaricus and Lactobacillus
      delbrueckii subsp. lactis by SDS-PAGE of cell-wall proteins.
AB  - AIMS: In the present study, a method based on SDS-PAGE fingerprinting of surface
      layer proteins was developed to identify Lactobacillus delbrueckii subsp.
      bulgaricus and subsp. lactis dairy isolates. METHODS AND RESULTS: The two
      subspecies, identified by species-specific PCR, were characterized by different
      SDS-PAGE cell-wall protein profiles; subspecies bulgaricus showed one band of
      about 31 kDa which, in some cases, was observed at a doublet, and subspecies
      lactis showed one band of about 21 kDa or 18 kDa. CONCLUSION: The sensitivity of
      this procedure for discriminating between the two subspecies was very high. The
      different types of SDS-PAGE profile for cell-wall proteins of the strains studied
      in this work did not seem to be correlated to the different dairies of origin.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The method appears to be an efficient
      taxonomic tool. It has the advantage of easy gel interpretation over
      fingerprinting of whole-cell protein extracts, and may be used as an alternative
      to established PCR-based techniques which, though rapid and safe, require
      expensive instruments and reagents.

PMID- 11328506
TI  - G1 antigen: a cell-surface immunoprotective 96 kDa glycoprotein from the virulent
      fish pathogen Enterococcus seriolicida, its purification and characterization.
AB  - Strains of the fish pathogen Enterococcus seriolicida were identified as
      agglutinating and non-agglutinating, according to their reaction with anti-serum
      raised against type strain YT-3 (ATCC49156). The non-agglutinating strains are
      highly pathogenic in contrast to agglutinating strains. A 96 kDa immunoprotective
      glycoprotein G1 antigen from non-agglutinating Ent. seriolicida strain SS91-014
      (N) was purified and characterized. The purification procedure entailed
      extraction of antigen by glass bead agitation, 80% (NH4)(2)SO4 precipitation, gel
      filtration and electroelution. An immunofluorescence microscopy study using
      monoclonal antibody M3A5 raised against G1 antigen revealed that G1 antigen is
      present only on the cell surface of non-agglutinating strains. Therefore, the G1
      antigen of virulent Ent. seriolicida could be a potential candidate for
      protective vaccine against enterococcosis in fish.

PMID- 11328509
TI  - Forecasting physician supply and demand.

PMID- 11328507
TI  - Association of PCR and feeding bioassays as a large-scale method to screen
      tropical Bacillus thuringiensis isolates for a cry constitution with higher
      insecticidal effect against Spodoptera frugiperda (Lepidoptera: Noctuidae)
      larvae.
AB  - AIMS: To verify whether the presence of any of the cry1C, 1D, 1E and 1F genes
      could be associated with high toxicity against fall armyworm. METHODS AND
      RESULTS: A sample of 60 strains from a large collection of tropical Bacillus
      thuringiensis (B.t.) isolates was subjected to feeding bioassays and gene
      specific PCR. Positive amplification of cry-specific fragments, so confirmed by
      sequencing, revealed that cry1C was ubiquitous and distributed among high and low
      mortality classes, cry1D was underrepresented and showed no clear association to
      high toxicity, and cry1F was not detected. The presence of cry1E significantly
      correlated to high levels of insecticidal activity, as estimated by linear
      regression analysis. CONCLUSION: The PCR amplification of cry1E-specific
      fragments alone appears to be sufficient to identify B.t. strains with high
      mortality levels against tropical armyworm. SIGNIFICANCE AND IMPACT OF THE STUDY:
      The approach presented is promising as a simple and efficient method for first
      tier, marker-assisted screening of environment-specific B.t. germplasm effective
      in controlling a single target pest.

PMID- 11328510
TI  - Medical revalidation and education--directed self-learning.

PMID- 11328511
TI  - Developing clinical teachers and their organizations for the future of medical
      education.

PMID- 11328512
TI  - Measurement of clinical reflective capacity early in training as a predictor of
      clinical reasoning performance at the end of residency: an experimental study on
      the script concordance test.
AB  - BACKGROUND: The script concordance (SC) test was conceived to measure knowledge
      organization, the presence of links between items of knowledge which allow for
      interpretation of data in clinical decision making situations. Earlier studies
      have shown that the SC test has good psychometric qualities and overcomes some of
      the limitations of simulation clinical testing. This study explores the
      predictive validity of the test. OBJECTIVES: To verify whether scores obtained by
      students at the end of clerkship predict their clinical reasoning performance at
      the end of residency. DESIGN: Comparison of scores obtained on a SC test taken at
      the end of clerkship with those obtained 2 years later at the end of residency on
      two clinical reasoning assessments of known validity, called the short-answer
      management problems (SAMPs) and the simulated office orals (SOOs), and an
      objective structured clinical examination (OSCE) aimed at assessing hands-on
      skills and clinical reasoning. Data were treated by Pearson correlation analysis.
      SUBJECTS AND SETTING: A cohort of 24 students from a medical school in Quebec was
      followed up to the end of their residency in family medicine, completed in
      several schools across Quebec. RESULTS: The observed Pearson correlation
      coefficients of the SC test were statistically significant (0.451, P=0.013;
      0.447; P=0.015) when compared with the SAMPs and the SOOs, respectively. They
      were not statistically significant (0.340, P=0.052) when compared with the OSCE.
      CONCLUSION: The authors assumed that the richness of knowledge organization, as
      indicated by SC test scores, would predict part of the performance on the
      measures of clinical reasoning (SAMP and SOO), but would predict less well
      performance on the OSCE which measures both clinical skills and clinical
      reasoning. Data found in the study are coherent with this hypothesis. This is
      evidence in favour of the construct validity of the SC test. It also indicates
      that, in the context of certification assessment, if a candidate has shown good
      organization of clinical knowledge at an early point in training, it can be
      expected that he/she will show good organization at subsequent measurements of
      this kind of knowledge. This appears to be true even if the later measures bear
      on a wider clinical domain.

PMID- 11328513
TI  - Teaching in the new NHS: the specialised ward based teacher.
AB  - OBJECTIVES: To evaluate the effects of introducing specialised ward based
      teachers (WBTs) who had a broad remit to improve third year medical
      undergraduates' clinical experience. DESIGN: Quantitative and qualitative methods
      including interviews with WBTs, participating consultants and SIFT co-ordinator;
      student questionnaire and evaluations; analysis of Objective Structured Clinical
      Examination (OSCE) scores to ascertain if exposure to WBTs affected OSCE scores.
      SETTING: Two university teaching hospitals. PARTICIPANTS: Third year
      undergraduate medical students from one school of medicine; four WBTs; 25
      consultants; SIFT co-ordinator. MAIN OUTCOME MEASURES: Student evaluations.
      Student questionnaires. Student OSCE scores. Interview data. RESULTS: WBTs had a
      demonstrable effect on student performance in OSCE examinations. 94% of students
      either agreed or strongly agreed that WBTs had helped them develop their
      examination skills and 87% either agreed or strongly agreed that WBTs had helped
      them develop their history taking skills. Interview data indicated that the
      consultants and SIFT co-ordinator considered that WBTs made an important
      contribution to clinical teaching. CONCLUSIONS: This study suggests that
      specialised WBTs are one way to manage clinical experience and enhance learning
      of undergraduate medical students. As clinical teaching moves into earlier parts
      of the undergraduate curriculum and into the community there is potential for
      this role to be developed.

PMID- 11328514
TI  - Examiner fatigue in communication skills objective structured clinical
      examinations.
AB  - CONTEXT: The assessment of undergraduates' communication skills by means of
      objective structured clinical examinations (OSCEs) is a demanding task for
      examiners. Tiredness over the course of an examining session may introduce
      systematic error. In addition, unsystematic error may also be present which
      changes over the duration of the OSCE session. AIM: To determine the strength of
      some sources of systematic and unsystematic error in the assessment of
      communication skills over the duration of an examination schedule. METHODS:
      Undergraduate first-year medical students completing their initial summative
      assessment of communication skills (a four-station OSCE) comprised the study
      population. Students from three cohorts were included (1996-98 intake). In all 3
      years the OSCE was carried out identically. All stations lasted 5 minutes with a
      simulated patient. Students were assessed using an examiner (content expert) and
      a simulated-patient evaluation tool, the Liverpool Communication Skills
      Assessment Scale (LCSAS) and the Global Simulated-patient Rating Scale (GSPRS),
      respectively. Each student was assigned a time slot ranging from 1 to 24, where
      1, for example, would denote that the student entered the exam first and 24
      indicates the final slot for entry into the examination. The number of students
      who failed this exam was noted for each of the 24 time slots. A control set of
      marks from a communication skills written exam was also adopted for exploring a
      possible link with the time slot. Analysis was conducted using graphical display,
      covariate analysis and logistic regression. RESULTS: No significant relationship
      was found between the schedule point that the student entered the OSCE exam and
      their performance. The reliability of the content expert and simulated-patient
      assessments was stable throughout the session. CONCLUSION: No evidence could be
      found that duration of examining in a communication OSCE influenced examiners and
      the marks they awarded. Checks of this nature are recommended for routine
      inspection to confirm a lack of bias.

PMID- 11328515
TI  - Graduate status and age at entry to medical school as predictors of doctors'
      choice of long-term career.
AB  - OBJECTIVE: To determine whether graduate entry to medical school, taking an
      intercalated degree during medical school, and age at entry to medical school are
      related to choice of eventual career. DESIGN: Postal questionnaires. SETTING:
      United Kingdom (UK). SUBJECTS: All doctors who qualified in the UK in 1993 or
      1996. RESULTS: We analysed whether graduate status and age on entry to medical
      school, and taking an intercalated degree during medical school, were predictors
      of the choice of eventual career, adjusting for differences by sex, year of
      qualification and medical school. General practice was the career choice of 27.0%
      (79/293) of graduate entrants and 21.6% (1095/5073) of non-graduate entrants, a
      difference of borderline significance (P=0.04). Of the non-graduate entrants,
      general practice was the career choice of 15.3% (319/2081) of doctors who took an
      intercalated degree and 25.9% (776/2992) of doctors who did not (P < 0.001).
      Within the hospital specialties, those who took an intercalated degree were more
      likely than others to choose the hospital medical specialties or pathology. Age
      alone was not a predictor for choice of any area of practice. CONCLUSIONS: There
      was no evidence of an association between age at entry to medical school and
      choice of eventual career. Graduates at entry to medical school were a little
      more likely than non-graduates to choose general practice but the relationship
      was not a strong one. In these respects, changing the entry profile of medical
      students is unlikely to result in major shifts of career choice towards general
      practice.

PMID- 11328516
TI  - Practice-based criteria for assessing anaesthetists' habits of action: outline
      for a reflexive turn in practice.
AB  - BACKGROUND: From an ecological perspective, we have demonstrated two distinct
      logics of practice in anaesthesia. One reflected attitudes characteristic of
      traditional medical thinking, while the other an insight into the uncertainty of
      actual situations. OBJECTIVE: We explored interactions between anaesthetists and
      patients, i.e. anaesthetist's habit of action. By tools we mean information,
      drugs, and concepts. METHODS: For studying the expert anaesthetists' habits of
      action in clinical circumstances, wide-ranging material was necessary including
      video recordings, documented observations and interviews. For each anaesthesia,
      characteristic cycles between perceived information and regulative actions were
      constructed. Together with meanings of distinct actions, they constituted the
      material for analysis of the criteria for evaluation. RESULTS: Besides
      differentiating the two habits of action, the criteria might provide a
      perspective for assessing trainees' performances. The 'reactive' habit of action
      was qualified by conservative and monological ways of using tools and reluctance
      to construct subjective evaluations. A failure to recognise the semantic aspect
      of information contributed to the absence of learning. The 'interpretative' habit
      of action, however, was qualified by creative and interactive use of tools.
      Ongoing sense-making and anticipation were achieved through cumulative learning
      based on a dialogical and reflective way of constructing subjective
      interpretations. CONCLUSION: Professional behaviour was defined through
      selectivity, interpretation, and judgement. To argue for a professional artistry
      view is to argue for how we should use our conceptual and material tools in
      striving for excellence.

PMID- 11328517
TI  - The face validity of a final professional clinical examination.
AB  - OBJECTIVE: To develop new methods of evaluating face validity in the context of a
      revised final professional examination for medical undergraduates, organized on
      three sites, over 2 days. METHODS: The opinion of the students and examiners was
      surveyed by Likert-style questionnaires, with additional open comments. Expert
      opinion was gathered from external examiner reports and a recent Quality
      Assurance Agency (QAA) Subject Review Report. RESULTS: The questionnaires had an
      overall response rate of 84%. Internal reliability, assessed by comparing
      responses to appropriate questions, was good with an equivalence of 45% (weighted
      kappa 0.54) for the students and 33% (weighted kappa 0.41) for the assessors.
      There was little evidence of inconsistency between days or sites. The majority of
      the opinions from the students, examiners and external experts were positive.
      Negative comments related to time pressure and case mix. CONCLUSION: The
      measurement of face validity proved feasible and valuable and will assist in the
      further development of the course and the examination.

PMID- 11328518
TI  - Setting performance standards for medical practice: a theoretical framework.
AB  - BACKGROUND: The assessment of performance in the real world of medical practice
      is now widely accepted as the goal of assessment at the postgraduate level. This
      is largely a validity issue, as it is recognised that tests of knowledge and in
      clinical simulations cannot on their own really measure how medical practitioners
      function in the broader health care system. However, the development of standards
      for performance-based assessment is not as well understood as in competency
      assessment, where simulations can more readily reflect narrower issues of
      knowledge and skills. This paper proposes a theoretical framework for the
      development of standards that reflect the more complex world in which experienced
      medical practitioners work. METHODS: The paper reflects the combined experiences
      of a group of education researchers and the results of literature searches that
      included identifying current health system data sources that might contribute
      information to the measurement of standards. CONCLUSION: Standards that reflect
      the complexity of medical practice may best be developed through an "expert
      systems" analysis of clinical conditions for which desired health care outcomes
      reflect the contribution of several health professionals within a complex, three
      dimensional, contextual model. Examples of the model are provided, but further
      work is needed to test validity and measurability.

PMID- 11328519
TI  - Career aspirations of house officers in Lagos, Nigeria.
AB  - OBJECTIVE: To identify the career aspirations of interns (house officers) working
      in two hospitals in Lagos, Nigeria. METHODS: All house officers working in the
      Lagos University Teaching Hospital and the General Hospital, Ikeja were invited
      to participate in a cross sectional survey. A self-administered questionnaire was
      used to collect data. RESULTS: Specialization choice was evident in 97.1% of the
      interns while they were undergraduates but this declined to 82.9% on qualifying,
      though chosen specialties did not vary much between both periods. The preferred
      specialties were surgery (18.1%), obstetrics and gynaecology (18.1%), paediatrics
      (9.5%) and dental sciences (10.5%). Doctors who were below the age of 26 years
      were significantly more likely to want to specialize than others (P=0.017).
      Furthermore, respondents who had no regrets about selecting medicine as a career
      were significantly more willing to specialize than others (P=0.013). The major
      reasons for wanting to specialize were interest in specialty (72.4%), job
      satisfaction (67.6%) and bright prospects in selected field (54.3%). However,
      14.4% no longer wanted to practise medicine while 69% would have liked to leave
      Nigeria, mainly for the United States of America. Financial considerations were a
      major reason for both groups. CONCLUSION: Surgery, obstetrics and gynaecology
      continue to attract young doctors to the detriment of other specialties.
      Financial considerations are also a key determinant of with regard to place of
      future practice.

PMID- 11328520
TI  - Issues of intervention aimed at preventing prospective surplus of physicians in
      Japan.
AB  - OBJECTIVES: In Japan, regulatory intervention aimed at preventing a prospective
      surplus of physicians is an important medical issue. The study committees
      organized by the Ministry of Health and Welfare (MHW) in 1986, 1993 and 1998,
      concluded that the number of physicians would exceed demand for their services in
      the future. As a result, the government planned to reduce the number of medical
      students. However, MHW has not been successful in the intervention so far, as
      shown by the fact that their initial plan for a 10% reduction in the number of
      students enrolled in medical school has not been attained. In this paper, we
      examine why the MHW policy failed. METHODS: We reviewed those forecasts performed
      by past MHW study committees and examined whether the government policy of
      controlling physician training was appropriate. Additionally, we did a
      preliminary projection of specialty-specific demand for physician services as a
      reference for future physician manpower policies in Japan. RESULTS: We found that
      both conflicts among various interest groups and a lack of precise projections of
      physician services hampered the proper formation and implementation of a
      physician manpower policy in Japan. CONCLUSIONS: It might be necessary to examine
      the appropriateness of the MHW policy in reducing the overall number of students
      enrolled in medical schools. As a first step in formulating and implementing a
      physician manpower policy, we should begin to consolidate the necessary data to
      conduct precise and proper projections of future physician demand.

PMID- 11328521
TI  - Country report: Australia.
AB  - The last 10 years has been an interesting time for Australian medical education
      despite reduced funding. WORKFORCE: There are five main workforce trends: a
      rural/urban maldistribution, a need for more specialists, public hospital
      staffing difficulties, increasing female practitioners and under-representation
      of indigenous practitioners. ISSUES FACING THE DEANS: Lack of resources is a
      problem facing Deans, with pressure for clinical service in teaching hospitals.
      Entrepreneurial activities have been undertaken including the enrollment of
      overseas students. Medical schools have also responded to important government
      initiatives. DEVELOPMENTS IN MEDICAL EDUCATION: Australia's 11 medical schools
      have undergone significant reform in the last decade. There is a mix of four
      (graduate), five and six year courses. AUSTRALIA'S NEW MEDICAL SCHOOL: James Cook
      University opened the first medical school in northern Australia in 2000. The
      School admits students from rural, northern Australian and indigenous
      backgrounds. It has a strong regional mission. RURAL AND COMMUNITY-BASED
      EDUCATION: Government funding to address the maldistribution of the workforce has
      led to the establishment of rural clubs, Departments of Rural Health and
      community-based programs. THE FIRST TWO POSTGRADUATE YEARS: There have been
      recent moves to improve education in the two years following graduation. This
      includes the initiation of national projects in curriculum and assessment.
      POSTGRADUATE AND CONTINUING MEDICAL EDUCATION: Postgraduate programs in Australia
      are being reformed to build on the changes in undergraduate education. CME is
      also under review. CONCLUSION: Australian medical educators should build on the
      recent reforms and take on some of the new directions in medical education.

PMID- 11328522
TI  - Time to learn: the outlook for renewal of patient-centred education in the
      digital age.
AB  - BACKGROUND: Major forces in society and within health systems are fragmenting
      patient care and clinical learning. The distancing of physician and trainee from
      the patient undermines learning about the patient-doctor relationship. The
      disconnection of care and learning from one successive venue to another impedes
      the ability of trainees to learn about illness longitudinally. METHODS: As a
      conceptual piece, our methods have been those of witnessing the experiences of
      patients, practitioners, and students over time and observing the impact of
      fragmented systems and changing expectations on care and learning. We have
      reflected on the opportunities created by digital information systems and
      interactive telemedicine to help renew essential relationships. RESULTS: Although
      there is, as yet, little in the literature on educational or health outcomes of
      this kind of technological enablement, we anticipate opportunities for a renewed
      focus on the patient in that patient's own space and time. Multimedia
      applications can achieve not only real-time connections, but can help construct a
      "virtual patient" as a platform for supervision and assessment, permitting
      preceptors to evaluate trainee-patient interactions, utilization of Web-based
      data and human resources, and on-line professionalism. CONCLUSIONS: Just as
      diverse elements in society are capitalizing upon digital technology to create
      advantageous relationships, all of the elements in the complex systems of health
      care and medical training can be better connected, so as to put the patient back
      in the centre of care and the trainee's ongoing relationship to the patient back
      in the centre of education.

PMID- 11328523
TI  - The use of focus group interviews in Asian medical education evaluative research.
AB  - OBJECTIVE: To evaluate the use of focus group interviews in Asian medical
      education evaluative research. METHODS: Randomly selected medical students were
      invited to participate in 30 focus group interviews to provide in-depth data
      about the effect on their learning of the introduction of early clinical skills.
      Efforts were made to meet all the students to help them understand the objectives
      of the focus group. Confidentiality was emphasised and a non-faculty interviewer
      was recruited for the interviews. RESULTS: The students considered the use of
      focus groups to be a more meaningful way of collecting students' opinions than
      other methods, for example structured questionnaire, because it allowed an
      interactive discussion. They also felt that having an independent non-faculty
      interview moderator had encouraged them to express their opinions more candidly
      during the interviews. CONCLUSION: The use of focus group interviews among Asian
      medical students for evaluative research is practical and efficient.

PMID- 11328524
TI  - What we want to do can drive what we need to learn.

PMID- 11328525
TI  - WFME task force on defining international standards in basic medical education.

PMID- 11328526
TI  - Communication skills teaching--the student's hidden feelings.

PMID- 11328527
TI  - Genetic analysis of pancreatic duct hyperplasia in Otsuka Long-Evans Tokushima
      Fatty rats: possible association with a region on rat chromosome 14 that includes
      the disrupted cholecystokinin-A receptor gene.
AB  - An Otsuka Long-Evans Tokushima Fatty (OLETF) strain of rat spontaneously
      developed hyperglycemia, hyperinsulinemia, insulin resistance and mild obesity,
      which had been studied as animal model for type II diabetes mellitus (T2DM).
      Recently, we observed that this strain coincidentally developed atypical
      hyperplasia of the choledocho-pancreatic ductal epithelium with a complete
      incidence. In an effort to locate genes responsible for this hyperplasia, we
      prepared 288 backcross progeny from a mating between OLETF rats and BN rats
      (which do not develop hyperplasia), and performed a genome-wide scan using 207
      polymorphic genetic markers. We observed a prominent association of hyperplasia
      with a region involving a marker locus D14Mit4 (P = 0.00020, Fisher's exact test)
      and Cckar (the cholecystokinin-A receptor gene; P = 0.00025, Fisher's exact test)
      which is known to be disrupted in an OLETF strain. Our findings indicated that
      epithelial hyperplasia of the choledocho-pancreatic duct is associated with a
      region on rat chromosome 14 around the Cckar gene in an additive fashion with
      another two susceptible loci, each on chromosome 9 and 7. This implied the
      possibility that Cckar deficiency could result in a predisposition towards
      pancreatic duct hyperplasia.

PMID- 11328528
TI  - Apoptotic bodies in the cerebellum of Japanese patients with Creutzfeldt-Jakob
      disease.
AB  - The aim of this study was to provide morphological evidence for neuronal
      apoptosis in Creutzfeldt-Jakob disease (CJD) using hematoxylin-eosin (HE)-stained
      specimens. A microscopic examination showed typical apoptotic bodies were found
      in the granular layer of the cerebellum in 13 of 14 Japanese patients with CJD,
      while no apoptotic bodies were observed in any other areas of the examined CJD
      brains. Most of the fragmented nuclei of the apoptotic cells were labeled by in
      situ end-labeling of fragmented DNA, terminal deoxynucleotidyl transferase
      mediated dUTP-biotin nick-end labeling. To the authors' knowledge, this is the
      first report demonstrating neuronal apoptotic bodies in the human
      neurodegenerative disorders on HE-stained sections. The present findings indicate
      that apoptosis plays a major role in the neuronal loss of the cerebellar granule
      cells in CJD.

PMID- 11328529
TI  - Distribution of peripheral nerve terminals in the small and large intestine of
      congenital aganglionosis rats (Hirschsprung's disease rats).
AB  - The congenital aganglionosis rat is considered to be an animal model of
      Hirschsprung's disease. The mutants had a long constricted segment (from distal
      ileum to rectum) below the dilated distal ileum. In the dilated region,
      synaptophysin-immunoreactivity (IR) was almost preserved in all layers of the
      intestinal wall. In the constricted distal ileum and oral proximal colon,
      synaptophysin-IR was scarce in all layers, including the circular and
      longitudinal muscle layers. In the anal proximal and distal colon, synaptophysin
      IR was almost scarce in the circular muscle layer (CML). An ultrastructural study
      confirmed that almost no terminals were found in the CML of any regions of
      constricted intestine. Therefore, the CML in any region of a constricted segment,
      is presumed to be poor innervation. However, a few synaptophysin-IR were found in
      the longitudinal muscle layer (LML) of an anal part of a constricted segment. An
      ultrastructural study also confirmed that some terminals were observed in the LML
      of this segment. The present study suggested that denervated CML is related to
      the production of constricted segment, irrespective of the presence or absence of
      terminals in the LML.

PMID- 11328530
TI  - Thymidine phosphorylase expression causes both the increase of intratumoral
      microvessels and decrease of apoptosis in human esophageal carcinomas.
AB  - Thymidine phosphorylase (dThdPase)/platelet-derived endothelial cell growth
      factor, is expressed at higher levels in tumor tissues compared to the adjacent
      normal tissues in a variety of human carcinomas. The higher expression is
      associated with an increase of intratumoral microvessel density (IMVD) and an
      unfavorable patient prognosis. We examined the role of dThdPase in apoptosis,
      IMVD, P53 expression and patient prognosis of human stages II and III esophageal
      squamous cell carcinomas (SCC). dThdPase expression was noted in 52 of the 78
      esophageal SCC (66.7%), regardless of tumor stages and histologic grades. Mean
      IMVD was 117.9 +/- 32.6 in the dThdPase-positive cases and 103.1 +/- 21.5 in the
      dThdPase-negative cases, the value being significantly higher in the former (P <
      0.05). Similarly, median (range) apoptotic index (AI: percentage of apoptotic
      cells) was significantly lower in the dThdPase-positive SCC, 1.8 (0.4-6.5), than
      in the dThdPase-negative SCC, 3.7 (0.6-7.0) (P < 0.01). AI and IMVD showed a
      significant inverse correlation (r = - 0.31, P = 0.005). There was also no
      significant difference in the frequency of P53 expression between the dThdPase
      positive SCC and the negative SCC. No statistical difference was noted regarding
      the postoperative survival rate between the dThdPase-positive and the negative
      SCC. Although dThdPase expression was not associated with patient prognosis, the
      expression provided an advantage for tumor growth of human esophageal SCC, not
      only by increasing the intratumoral microvessels, but also attenuation of
      apoptosis, which might occur via a p53 gene-independent pathway.

PMID- 11328531
TI  - Histologic heterogeneity and mucin phenotypic expression in early gastric cancer.
AB  - Although the major histologic type in small gastric cancers, less than 10 mm in
      diameter, is differentiated-type adenocarcinoma (D.Ca), the incidence of D.Ca and
      that of undifferentiated-type adenocarcinoma (UD.Ca) is almost the same in all
      early gastric cancers. Histologic conversion from D.Ca to UD.Ca has been
      speculated, however, a detailed examination of this phenomenon has not yet been
      performed. Three-hundred and 51 early gastric cancers (D.Ca, 150 (42.7%) lesions;
      UD.Ca, 93 (26.4%) lesions; and mixed differentiated and undifferentiated type
      (D&UD.Ca), 108 (30.8%) lesions; tumor size less than 10 mm in diameter; 64
      lesions, more than 10 mm, 287 lesions) were examined histochemically with
      paradoxical concanavalin A type III and high-iron diamine-Alcian blue (pH 2.5),
      and immunohistochemically with antigastric mucin antibody. The associations
      between tumor size, tumor differentiation and phenotypic expression of mucin were
      examined. Regardless of the tumor size, mucin phenotypic expression in the
      mucosal lesions examined was preserved. Of 47 cancers with a gastrointestinal
      mucin phenotype (GIM type) or a gastric mucin phenotype (GM type) measuring less
      than 10 mm, 35 (74.5%) consisted of D.Ca and 12 (25.5%) of both D&UD.Ca and
      UD.Ca, while of 224 GIM or GM type cancers measuring more than 10 mm, 64 (28.6%)
      consisted of D.Ca and 160 (71.4%) of both D&UD.Ca and UD.Ca. Differences between
      these two groups were statistically significant (P < 0.001). Of 15 cancers with
      an intestinal mucin phenotype (IM type) measuring less than 10 mm, 12 (80.0%)
      consisted of D.Ca and three (20.0%) of both D&UD.Ca and UD.Ca, and of 50 IM type
      cancers measuring more than 10 mm, 35 (70.0%) consisted of D.Ca and 15 (30.0%) of
      both D&UD.Ca and UD.Ca. Differences between these two groups were not
      statistically significant. These findings suggest that small D.Ca showing gastric
      mucin expression may transform into UD.Ca during the progression of early gastric
      cancer.

PMID- 11328532
TI  - Expression of the hepatocyte growth factor/c-Met pathway is increased at the
      cancer front in breast carcinoma.
AB  - Expression of hepatocyte growth factor (HGF) and c-Met (HGF receptor) has been
      reported in many neoplasms. We investigated coexpression of HGF and c-Met to
      determine the role of the HGF/c-Met pathway in breast carcinoma, especially at
      the cancer front. Eighty-eight cases of carcinoma of the breast were studied by
      immunohistochemistry and by in situ hybridization for HGF and c-Met expression.
      The staining pattern was termed "front accentuation pattern" when it was most
      conspicuous at the cancer front. HGF and c-Met proteins were expressed in cancer
      and stromal cells, with autocrine and paracrine patterns. The front accentuation
      pattern of c-Met was observed in cancer cells, but not in stromal cells. The
      front accentuation pattern was not observed in HGF. Coexpression of HGF and c-Met
      at the cancer front was correlated with histologic grade, reduced patient
      survival and a high Ki-67 labeling index. Our findings suggest that the HGF/c-Met
      pathway acts primarily as a mitogen, especially at the cancer front, in a
      paracrine manner and affects some clinical factors, including patient survival.

PMID- 11328533
TI  - Glomerular crescents in renal amyloidosis: an epiphenomenon or distinct
      pathology?
AB  - There have been several reports of cases of renal amyloidosis with glomerular
      crescents. However, it is not clear whether the association is fortuitous or
      pathogenic related. The present study analyzed 105 cases of renal amyloidosis (61
      autopsy cases and 44 biopsy cases) and found glomerular crescents in 14 (13.3%)
      cases. Among the 14 cases with crescents, a female predominance was noted (male:
      female, 3: 11) and rheumatoid arthritis was the most common primary disease of
      amyloidosis. Immunohistochemical analysis demonstrated amyloid protein of AA type
      in 12 cases. According to the histologic classification, there were 11 cases of
      mesangial nodular type, which was almost exclusively accompanied by AA amyloid
      deposition. Of note, the incidence of crescents neither correlated with the
      extent of amyloid deposition nor the presence of nephrotic syndrome. By contrast,
      localization of amyloid deposition was closely related to crescent formation.
      Moreover, electron microscopic observation displayed rupture of the glomerular
      basement membrane at the site of amyloid deposition. Our results indicated that
      glomerular crescents were more frequently associated with renal amyloidosis than
      previously appreciated. Rupture of the fragile glomerular basement membrane by
      amyloid deposition, as revealed by immunostaining and electron microscopy, may be
      the mechanism of crescent formation. We suggest that glomerular crescents are a
      distinct pathology associated with renal amyloidosis, not fortuitous conditions.

PMID- 11328534
TI  - TP53 deleted cells in de novo glioblastomas using fluorescence in situ
      hybridization.
AB  - Glioblastoma (GBM) has been known to have two distinct genetic pathways of
      tumorigenesis. Secondary GBM shows frequent TP53 mutation, but de novo (primary)
      GBM is usually independent of TP53 alteration. However, the subpopulation of TP53
      altered cells in the latter tumor is obscure. In order to assess TP53 deleted
      cells in de novo GBM quantitatively, we performed dual color fluorescence in situ
      hybridization (FISH) for TP53 and centromere 17 in nine cases of de novo GBM with
      frozen surgical materials. Single TP53 signal cells indicating TP53 deletion were
      recognized in 8.7-35.6% (mean, 21.3%) among the nine cases. In addition,
      immunohistochemistry was performed for the Ki-67 antigen (MIB-1) and p53 protein
      in all nine cases. Labeling indices (LI) of MIB-1 ranged from 2.8 to 46.9% (mean,
      20.8%). Between the group with the more dense subpopulation of TP53 deleted cells
      (15% or more) by FISH and the group with less subpopulation than the former,
      these LI of MIB-1 demonstrated statistically significant difference (respective
      means, 28.2% and 6.1%; P < 0.05). Conversely, LI of p53 protein shown to be 0
      50.9% (mean, 24.9%) had no correlation with the subpopulation of TP53 deleted
      cells by FISH. Four cases who had higher LI of p53 protein (mean, 39.7%) than the
      subpopulation of TP53 deleted cells (mean, 12.7%), respectively, indicated the
      presence of many p53 protein immunoreactive cells without TP53 deletion. These
      results suggest that: (i) de novo GBM also has subpopulation of TP53 deleted
      cells; (ii) TP53 alteration, which may not be a major event, participates in cell
      proliferation of de novo GBM; and (iii) de novo GBM tends to have accumulation of
      wild-type p53 protein.

PMID- 11328535
TI  - Malignant adenomyoepithelioma of the breast: a non-tubular and matrix-producing
      variant.
AB  - Two women, aged 82 and 58 years old, cases 1 and 2, respectively, with the non
      tubular and matrix-producing variant of malignant adenomyoepithelioma (MAM) of
      the breast are described. The tumors were 20 and 35 mm in diameter, respectively,
      and had cut surfaces with a tan-white-colored appearance and vague lobulation.
      Although both tumors showed marked central necrosis and a high level of mitoses,
      the tumor cells had relatively monomorphous nuclei and exhibited only mild
      atypia. The invasive component was predominantly trabecular and lobular, and the
      intraductal component demonstrated a focal-comedo pattern. The cytoplasm of the
      tumor cells was rather scanty, vacuolar or pale with ill-defined borders. The
      tumor in case 2 contained intermingled spindle-shaped cells. The stroma of both
      tumors resembled that of pleomorphic adenoma, containing a myxoid and chondroid
      matrix and, in case 2, cartilage and mature bone. Immunohistochemical and
      ultrastructural analyses of both tumors revealed dual cytological
      differentiation, predominantly of myoepithelial cells with secretory epithelial
      cells intermingled haphazardly. Although these tumors resembled metaplastic
      carcinomas, particularly matrix-producing carcinomas, they showed marked
      myoepithelial differentiation without overt tubular differentiation, a pattern
      quite different from matrix-producing carcinomas and from the
      adenomyoepitheliomas reported so far. MAM of the breast, non-tubular and matrix
      producing variant, resembles epithelioid myoepithelial carcinoma of the salivary
      gland and has not been reported previously in the English literature.

PMID- 11328536
TI  - Multicentric telangiectatic osteosarcoma.
AB  - A rare case of multicentric telangiectatic osteosarcoma in a 29-year-old woman is
      described. A plain X-ray showed a pure osteolytic lesion of the navicular, cuboid
      and I, II, III cuneiform bones. On magnetic resonance images, a T1-weighted image
      showed heterogeneous low signal intensity. A T2-weighted image showed
      heterogeneous high signal change with multicentric cystic foci and fluid-fluid
      levels. Histologically, the lesion showed typical telangiectatic osteosarcoma
      with numerous atypical giant cells.

PMID- 11328537
TI  - Low-grade pulmonary myxoid sarcoma of uncertain histogenesis.
AB  - The present report describes an unusual case of low-grade pulmonary sarcoma with
      extensive myxoid change in a 60-year-old man. During 30 months, the tumor
      enlarged gradually and thereafter rapidly to 9 cm. Preoperative biopsy and
      cytology gave negative results. The resected mass, located at the periphery of
      the right upper lobe, was well circumscribed and showed gelatinous without
      necrosis or hemorrhage. Histologically, the tumor was composed of slightly
      atypical, spindle-shaped or stellate cells, which were loosely distributed within
      a prominent myxoid stroma. Epithelial differentiation was not seen. Lacunar
      structures were occasionally evident, but no cartilaginous matrix was seen.
      Mitotic figures were infrequent. Immunohistochemistry failed to clarify the
      nature of the neoplastic cells except vimentin positivity. Histochemically, the
      myxoid ground substance was composed of hyaluronic acid and acid
      mucopolysaccharide. Electron microscopy revealed no specific differentiation
      other than aggregates of filaments, which were seen in a number of neoplastic
      cells. Flow cytometric analysis of the neoplastic cells revealed a diploid
      pattern. These findings indicated that the neoplasm was a low-grade myxoid
      sarcoma; however, a definite diagnosis could not be made. The tumor might have
      been a variant of extraskeletal myxoid chondrosarcoma, especially considering the
      histochemical results.

PMID- 11328538
TI  - Tubal ectopic pregnancy associated with an adenomatoid tumor.
AB  - We present a case of coexistence of an ectopic pregnancy and an adenomatoid tumor
      in the same fallopian tube. The adenomatoid tumor is the most common benign
      neoplasm of the fallopian tube, and the vast majority of ectopic pregnancies
      occur in the fallopian tube. However, coexistence of these two conditions is
      extremely rare, and there has been only one previously reported case in the
      English literature. In the present case, the placental tissue, consisting of
      chorionic villi and decidua, was present in the ampulla, and the adenomatoid
      tumor was found in the myosalpinx, just proximal to the implantation site,
      replacing a large part of the myosalpinx. The close spatial relationship of these
      two lesions suggests that an adenomatoid tumor could have interfered with
      transportation of the fertilized ovum through the tube, possibly via impaired
      contractile activity of the myosalpinx, and consequently caused the ectopic tubal
      pregnancy.

PMID- 11328539
TI  - Colonic intra-epithelial carcinoma occurring in a hyperplastic polyp via a
      serrated adenoma.
AB  - We present a case of intra-epithelial carcinoma occurring in a serrated adenoma
      of the colon. The pedunculated polyp, which measured 12 x 10 x 6 mm, was
      endoscopically removed from the ascending colon of a 78-year-old woman.
      Histologically, the polyp mainly consisted of serrated adenomatous glands, and
      had foci of intra-epithelial carcinoma at the top. Hyperplastic (metaplastic)
      areas were also present in both borders between the serrated adenomatous area and
      the surrounding normal mucosa. A sequential increase in the degree of dysplasia,
      and in the number of nuclei positively reactive for Ki-67 and p53 was evident
      from the hyperplastic areas toward the foci of carcinoma. The polyp described
      here may represent a carcinogenic potential of hyperplastic polyp via serrated
      adenoma.

PMID- 11328540
TI  - Pathology in Germany and Finland: a brief report of the delegates of the Japanese
      Society of Pathology.

PMID- 11328541
TI  - Ethnicity and recurrence of focal segmental glomerulosclerosis.

PMID- 11328542
TI  - Pretransplantation voiding cystography is not necessary for all potential
      pediatric kidney recipients.

PMID- 11328543
TI  - Tacrolimus and diarrhea: pathogenesis of altered metabolism.

PMID- 11328544
TI  - Indications for pediatric intestinal transplantation: a position paper of the
      American Society of Transplantation.
AB  - Parenteral nutrition represents standard therapy for children with short bowel
      syndrome and other causes of intestinal failure. Most infants with short bowel
      syndrome eventually wean from parenteral nutrition, and most of those who do not
      wean tolerate parenteral nutrition for protracted periods. However, a subset of
      children with intestinal failure remaining dependent on parenteral nutrition will
      develop life-threatening complications arising from therapy. Intestinal
      transplantation (Tx) can now be recommended for this select group. Life
      threatening complications warranting consideration of intestinal Tx include
      parenteral nutrition-associated liver disease, recurrent sepsis, and threatened
      loss of central venous access. Because a critical shortage of donor organs
      exists, waiting times for intestinal Tx are prolonged. Therefore, it is essential
      that children with life-threatening complications of intestinal failure and
      parenteral nutrition therapy be identified comparatively early, i.e. in time to
      receive suitable donor organs before they become critically ill. Children with
      liver dysfunction should be considered for isolated intestinal Tx before
      irreversible, advanced bridging fibrosis or cirrhosis supervenes, for which a
      combined liver and intestinal transplant is necessary. Irreversible liver disease
      is suggested by hyperbilirubinemia persisting beyond 3-4 months of age combined
      with features of portal hypertension such as splenomegaly, thrombocytopenia, or
      prominent superficial abdominal veins; esophageal varices, ascites, and impaired
      synthetic function are not always present. Death resulting from complications of
      liver failure is especially common during the wait for a combined liver and
      intestinal transplant, and survival following combined liver and intestinal Tx is
      probably lower than following an isolated intestinal transplant. The incidence of
      morbidity and mortality following intestinal Tx is greater than that following
      liver or kidney Tx, but long-term survival following intestinal Tx is now at
      least 50-60%. It is probable that outcomes shall improve in the future with
      continued refinements in operative technique and post-operative management,
      including immunosuppression.

PMID- 11328545
TI  - Rotavirus infection as cause of tacrolimus elevation in solid-organ-transplanted
      children.
AB  - Rotavirus (RV) is the most common cause of diarrheal illness in children. We
      report three solid-organ-transplanted patients in whom RV infection caused
      increased trough levels of the immunosuppressive macrolide tacrolimus (TAC) by
      mechanisms that are still under investigation. The virus was detected for longer
      in the feces of these patients than in infants not receiving immunosuppressive
      therapy. In association with short-term monitoring of blood trough levels of TAC,
      the dosage should be reduced early if symptoms of an acute gastroenteritis are
      present.

PMID- 11328546
TI  - Reasons why some children receiving tacrolimus therapy require steroids more than
      5 years post liver transplantation.
AB  - Tacrolimus is a potent immunosuppressive agent and has been used in liver
      transplantation (LTx) for nearly a decade. More than 70% of children can be
      maintained on tacrolimus monotherapy, without steroids, by the end of 1 yr post
      Tx. This freedom from steroids does not appear to change significantly in
      subsequent years. The use of steroids has obvious metabolic and cosmetic
      disadvantages, besides affecting linear growth in children. The present study
      identifies why some children still require steroid therapy after successful LTx.
      One hundred and sixty-six consecutive pediatric patients who had undergone
      primary LTx between October 1989 and December 1992, were included in this study.
      Follow-up ranged from 6 to 9 yr (mean 7.5 +/- 0.8 yr). One hundred and forty-one
      children were alive in November 1998 and these patients constituted the study
      group. Their current rate of prednisone use, reason for prednisone use, and
      prednisone dose were examined retrospectively. Of the 141 patients, 139 (98.5%)
      had stopped taking steroids at some time-point after LTx. Thirteen patients (9%)
      were off immunosuppression altogether (group I), 97 were undergoing tacrolimus
      monotherapy (group II), and the remaining 31 were receiving therapy with steroids
      and tacrolimus (group III). The mean prednisone dose at the last follow-up was
      6.5 +/- 4.9 mg/day (median 5.0 mg/day). In group III, two children were never
      weaned off steroids because of inadequate follow-up (both lived outside the
      country), and the remaining 29 children completely stopped steroid therapy at
      some time-point after LTx; however, prednisone was re-introduced for clinically
      suspected or biopsy-proven rejection in 24. Seven children in group III had
      completely stopped immunosuppressive therapy either as part of an
      immunosuppression reduction protocol (n = 3) or for suspected or proven post
      transplant lymphoproliferative disorder (PTLD) (n = 4). In eleven of the 18
      children in group III, requirement of steroid for rejection was thought to be
      related, in part, to non-compliance. In three children in group III, steroids
      were re-introduced for renal dysfunction, and two of these patients subsequently
      received a kidney Tx. In one child with cerebral ischemia, steroids were used to
      reduce brain edema, and another child had features of auto-immune hepatitis.
      Hence, almost all children can be weaned off steroids when tacrolimus is used as
      primary immunosuppression after primary LTx. However, approximately 22% of
      children may need re-institution of steroids because of late acute rejection or
      renal dysfunction. The concomitant use of other non-steroidal immunosuppressive
      agents with tacrolimus may further reduce the dose and rate of steroid use.

PMID- 11328547
TI  - Predictors for abnormal voiding cystourethrography in pediatric patients
      undergoing renal transplant evaluation.
AB  - The role of pretransplant voiding cystourethrography (VCUG) in adults has been
      questioned owing to the low prevalence of abnormal findings. As there are no
      studies evaluating the relevance of VCUG in children and because vesicoureteral
      reflux (VUR) occurs with higher prevalence in children, we performed a
      retrospective cohort study to identify any predictors for abnormal VCUG. We
      reviewed 271 consecutive renal transplants performed between 1980 and 1997. By
      logistic regression, the etiology of end-stage renal disease (ESRD) and age at
      transplantation (Tx) were strong predictors of abnormal pretransplant VCUG
      findings in children. On multi-variate analysis, children with urologic
      etiologies of renal disease had an odds ratio (OR) of 16.5 (p < 0.0001) for
      abnormal VCUG as compared to children with non-urologic or acquired causes of
      ESRD. Similarly, children transplanted when younger than 8 yr of age had an OR of
      3.0 (p = 0.0043) for having an abnormal VCUG when compared with older children.
      Finally, our analysis suggests that children with abnormal pretransplant VCUG
      findings, whether or not pretransplant surgical correction was performed, were
      over three-fold more likely to require post-transplant urologic surgery when
      compared to children with normal pretransplant VCUG. We conclude that urologic
      causes of ESRD and age under 8 yr are strong independent predictors of abnormal
      pretransplant VCUG findings, and that these findings are of clinical relevance
      both in deciding whether to pursue pretransplant VCUG and in the post-transplant
      course of the patient.

PMID- 11328548
TI  - Recurrent focal segmental glomerulosclerosis following renal transplantation in
      Korean pediatric patients.
AB  - The recurrence of focal segmental glomerulosclerosis (FSGS) in transplants is a
      well-known problem in pediatric renal transplantation (Tx). Recently, the race of
      the recipient was recognized as a major variable associated with disease
      recurrence. In view of this finding, we report on our single-center experience of
      FSGS recurrence in Korean children, an ethnically homogeneous Far East Asian
      population. Clinical records and renal biopsy specimens, both native and graft,
      were reviewed for all pediatric renal Txs (recipient age < or = 18 yr) performed
      at Seoul National University Hospital from 1984 to 1999. Twenty-two children with
      primary FSGS received 22 allografts for renal replacement. The mean age of
      disease onset in these patients was 5.9 yr. The grafts were from 12 living
      related, six living-unrelated, and four cadaveric donors, and all recipients were
      immunosuppressed with cyclosporin A (CsA)-based regimens. Post-transplant
      recurrence of FSGS was confirmed in nine patients (41%). Long-term graft survival
      in recurrent and non-recurrent groups was not significantly different. Risk
      factor analysis showed that patients with a disease duration shorter than 48
      months (odds ratio 11.7, 95% CI 1.53-89.1) and a glomerulosclerosis percentage of
      < 55% by renal biopsy (odds ratio 16.0, 95% CI 1.45-176) were at greater risk of
      disease recurrence. These results suggest that Korean children are similar to non
      African-American youngsters in the USA and Europe with respect to post-transplant
      recurrence of FSGS. The same may be true of other Far Eastern Asian children.

PMID- 11328549
TI  - Mycophenolate mofetil in pediatric heart transplant recipients: a single-center
      experience.
AB  - Mycophenolate mofetil (MMF) is emerging as an effective agent for the treatment
      of both established rejection and primary rejection prophylaxis in solid-organ
      transplantation (Tx). However, little data is available on the use of MMF in the
      pediatric population. We therefore report on our experience with MMF in 21
      pediatric heart transplant recipients. Data were obtained by retrospective chart
      review. Median age at time of review was 12.3 yr (range 11 months to 16.9 yr).
      Median age at Tx was 10.7 yr (range 55 days to 16.7 yr). MMF was started at a
      median of 4.3 months after Tx (range 1 day to 4.5 yr). At the time of MMF
      institution, all patients were concurrently on prednisone and azathioprine; 20 of
      these patients were also undergoing treatment with tacrolimus (median dose 0.18
      mg/kg, range 0.03-0.64 mg/kg) and one with cyclo-sporin A (10 mg/kg).
      Azathioprine was discontinued at the time of commencing MMF. The average MMF dose
      was 40 +/- 14 mg/kg. The rationale for switching to MMF included rejection
      (International Society for Heart and Lung Transplantation [ISHLT] 3A/B), 66%;
      inability to wean steroids, 14%; ABO blood group donor-recipient mismatch, 10%;
      coronary artery disease (CAD), 5%; and side-effects of immuno-suppression, 5%. Of
      the patients switched for rejection, 93% demonstrated resolved or improving
      rejection. Both ABO donor-recipient mismatch patients were started on
      tacrolimus/MMF as primary therapy and had no significant episodes of rejection.
      Two patients had rejection classified as unchanged (one with CAD, one treated
      with addition of sirolimus prior to improvement). Corticosteroids were
      successfully discontinued in 28% of patients, and 20% are currently on a reduced
      dose. Fourteen per cent developed significant rejection while attempting to
      reduce the steroid dose. Steroid reduction has not yet been attempted in 38% of
      patients. The following side-effects were reported in 38% of the patients:
      diarrhea, 10%; gastrointestinal discomfort, 20%; and leukopenia, 20%. Dose
      reduction or temporary discontinuation was required in 63% of the patients who
      experienced side-effects (24% of the total number of patients). Opportunistic
      infections developed in 10% (cryptococcus, cytomegalovirus). Hence, MMF appears
      to be effective for treatment of rejection in the pediatric heart transplant
      population and has an acceptable side-effect profile. In addition, it may have a
      role in primary rejection prophylaxis and may facilitate a reduced steroid dosage
      or a steroid-free immunosuppression regimen.

PMID- 11328550
TI  - Therapeutic drug monitoring of tacrolimus in pediatric liver transplant patients.
AB  - The clinical utility of tacrolimus monitoring in adults has been well documented.
      The present study compared tacrolimus monitoring in a pediatric population of 34
      liver transplant patients in four US centers with an adult population of 111
      patients in six US centers. Subjects (adult and pediatric) were evaluated, at
      defined intervals over 12 weeks post-transplantation (Tx), for tacrolimus trough
      concentrations and 12 additional laboratory chemistries. Pediatric patient and
      graft survival for the 12 weeks were 91% and 88%, respectively, as compared to
      97% and 93%, respectively, for the adult population. The mean oral dosage of
      tacrolimus for pediatric patients was 0.13 +/- 0.1 mg/kg/day at week 1, increased
      to 0.30 +/- 0.3 mg/kg/day by week 3 and remained constant for the remainder of
      the study. These dosages were two- to three-fold higher than the dosage used in
      the adult population. In contrast, the mean whole-blood trough concentration, as
      determined by PRO-Tractrade mark II enzyme-linked immunosorbent assay (ELISA),
      decreased from 11.3 +/- 5.1 ng/mL at week 1 to 6.3 +/- 3.7 ng/mL by week 12 and
      was not significantly different from the trough concentration in adults. The
      incidence and distribution of the clinical end-points for the pediatric subjects
      (rejection, nephrotoxicity, death, re-Tx) were different from those observed in
      adults. The total percentage of pediatric subjects reaching any end-point was
      74%, as compared to 54% in the adult population. These data indicate several
      differences between the adult and pediatric populations in their response to
      tacrolimus.

PMID- 11328552
TI  - Elevated tacrolimus trough levels in association with mycophenolate mofetil
      induced diarrhea: a case report.
AB  - The combination of tacrolimus (TAC) and mycophenolate mofetil (MMF) is frequently
      used for immunosuppression after organ transplantation (Tx), but the
      pharmacokinetics and interactions between the two drugs are poorly elucidated. We
      describe here the increase of TAC trough levels during MMF-induced diarrhea in a
      8-yr-old boy after kidney Tx. Early dose reduction of TAC, together with short
      term monitoring of TAC trough levels in the presence of diarrhea, is recommended.

PMID- 11328551
TI  - Hematologic abnormalities in children and young adults receiving tacrolimus-based
      immunosuppression following cardiothoracic transplantation.
AB  - To define the incidence, course, and etiology of hematologic abnormalities in
      children on tacrolimus-based immunosuppression, we reviewed records of 106
      transplant patients (70 heart, 16 heart and lung, 20 double lung), 0-21 yr of
      age, who were transplanted at the Children's Hospital of Pittsburgh from 1989 to
      1997. Fifty-four of the 106 patients (51%) developed 65 abnormal hematologic
      episodes (32 anemia, nine neutropenia, nine thrombocytopenia, 15 simultaneous
      anemia and neutropenia with or without thrombocytopenia). Common etiologies
      included: infections, post-transplant lymphoproliferative disease, and
      medications. Eleven episodes (seven anemia, one neutropenia, and three
      simultaneous anemia and neutropenia) had unclear etiologies and process of
      elimination suggested an association with tacrolimus. Interventions included
      filgrastim (effective in 15 of 15 patients, with resolution of neutropenia in a
      median of 5 days) and epoetin alfa (effective in five of 16 patients, including
      four of four patients with anemia possibly related to tacrolimus). Five patients
      (two with neutropenia and three with simultaneous neutropenia and anemia) were
      switched to cyclosporin A (CsA); rapid resolution occurred in four of the five
      patients, suggesting a possible association of the hematologic abnormalities with
      tacrolimus. In summary, hematologic abnormalities are common in children on
      tacrolimus-based immunosuppression. Most of these hematologic abnormalities are
      caused by common etiologies; however, a sub-population exists where tacrolimus
      may be the etiologic agent. Anemia and neutropenia respond to treatment with
      epoetin alfa and filgrastim. After thorough investigation, a trial switch to CsA
      may be warranted.

PMID- 11328553
TI  - Reversal of protein-losing enteropathy in a child with Fontan circulation is
      correlated with central venous pressure after heart transplantation.
AB  - We report on the reversal of protein-losing enteropathy (PLE) after heart
      transplantation (HTx) in a 10-yr-old boy with Fontan circulation, previously
      treated unsuccessfully with heparin for several months. The protein loss
      continued immediately after the Tx. During the following month, however, a
      gradual decrease in protein loss was observed, which correlated with a decrease
      in the inferior vena cava (IVC) pressure. The patient is doing well with a normal
      serum albumin level and a normal IVC pressure, 2 yr after Tx.

PMID- 11328554
TI  - An unusual case of fatal pulmonary allograft rejection.
AB  - This case report describes an atypical form of acute pulmonary allograft
      rejection that was refractory to conventional therapy. The rejection manifested
      primarily as interstitial lymphocytic infiltrates with little perivascular
      involvement. Despite aggressive therapy the patient died within 7 months of
      transplant. The timely recognition and treatment of unusual forms of allograft
      rejection is vital in the management of pulmonary transplant patients.

PMID- 11328555
TI  - Successful ribavirin therapy for life-threatening laryngeal papillomatosis post
      liver transplantation.
AB  - A 3-yr-old girl developed severe progressive juvenile laryngeal papillomatosis
      (JLP) 2 yr after liver transplantation (Tx) for biliary atresia. The papillomata
      were resistant to withdrawal of immunosuppression, to laser surgery, and to
      subcutaneous interferon (3 MU/m2, three times weekly), necessitating
      tracheostomy. Oral ribavirin therapy (25 mg/kg/day) in combination with no
      immunosuppression effectively prevented the rapid recurrence of JLP over 5 yr.
      Hence, oral ribavirin is a potentially useful therapy in this life-threatening
      situation and may also be of benefit in other children with severe JLP.

PMID- 11328556
TI  - Cryopreservation of embryos of farm animals.
AB  - This review contains two parts. The first part is devoted to the significant
      steps in cryopreservation of mammalian embryos with emphasis on cattle and sheep
      that serve as models of reference. These steps are: (1) shortening of cooling and
      warming processes; (2) addition and dilution of cryoprotectant in one step; (3)
      introduction of plastic straw as a freezing and dilution container; (4) the
      choice of ethylene glycol as the quite universal cryoprotectant because of its
      low toxicity and high permeability; (5) vitrification, a cryopreservation method
      which enable passage from the liquid to the solid state by extreme elevation of
      viscosity due to high concentration of cryoprotectants and very rapid cooling.
      There are several vitrification solutions which contain dimethyl sulphoxide,
      glycerol, ethylene glycol, or a mixture of them, as basic cryoprotectants. The
      second part considers some factors affecting the efficiency of cryopreservation
      concerning (i) the origin of embryos and (ii) the stage of development and
      species. The origin of embryos (in vivo versus in vitro): in vitro embryos show a
      chilling and freezing sensitivity associated with their lipid content which can
      be modified by the culture conditions. Both conventional freezing and
      vitrification have been used and it seems that vitrification is more adapted to
      in vitro embryos when some modifications of initial protocols are carried out,
      particularly the rate of cooling. Thus considerable progress has been achieved by
      using the open pulled straw method of Vajta which enables the use of a minimum
      volume of freezing medium (0.5 microl) and a very high cooling rate that permits
      rapid traversal of the damaging temperature zone, corresponding to chilling
      sensitivity. The stage of development and species: not only are there differences
      between species at the same stage of development but in the same species all
      stages of development do not survive equally under the same freezing protocol. In
      cattle for example, oocytes and early stages of development in vivo or in vitro
      do not survive whereas compacted morulae and blastocysts survive very well. In
      the pig hatched blastocysts survive better than the other stages. Horse embryos
      have special characteristics that pose problems for successful freezing. In
      conclusion, a lot of work remains to be done to define fundamental
      characteristics of embryos of certain species (pig, horse) and of embryos of some
      stages or of oocytes.

PMID- 11328557
TI  - Endocrine profiles and embryo quality in Japanese black cattle superovulated with
      human menopausal gonadotrophin and porcine follicle stimulating hormone.
AB  - Induction of superovulation using human menopausal gonadotriphin (hMG) in
      Japanese Black cattle can result in the recovery of a higher percentage of high
      quality embryos compared with that using porcine follicle stimulating hormone
      (FSH). In order to clarify the endocrinological mechanism involved in this
      discrepancy, 30 superovulation sessions of 17 Japanese Black cattle were studied.
      Fifteen cattle were super-stimulated with hMG (total 600 IU), and the remaining
      15 cattle were given FSH (total 20 mg). The plasma profiles of LH, estradiol
      17beta (E2) and progesterone (P4) were correlated, and the embryo quality was
      investigated. The total number of ova recovered and the number of transferable
      embryos tended to be larger in the hMG-treated group than in the FSH-treated
      group. The percentage of excellent embryos tended to be higher in the hMG-treated
      group than in the FSH-treated group (54.3 and 28.7%, respectively, p < 0.10). The
      E2 level increased during the first 3 days after the initial administration of
      either hMG or FSH and was higher in the hMG-treated group than in the FSH-treated
      group (p < 0.05). During this period, the E2 level could be categorized into one
      of the following three types according to whether it increased or decreased and
      according to the degree of increase or decrease: (1) increase by a factor of 1.2
      or more (quick increase type) (2) slight increase by a factor less than 1.2 (slow
      increase type), and (3) no increase (unstable increase type). In the group
      treated with hMG, 66.7% of the animals (10 of 15 cattle) showed a quick increase
      in the E2 level. However, in the FSH-treated group, 40% (six of 15) of the
      animals showed a slow increase in the E2 level. The plasma LH level increased
      dramatically 8 h prior to the peak level in both the hMG- and FSH-treated groups,
      and then it returned to the basal level 12 h later. After the administration of
      prostaglandin (PG)F2alpha, the LH peak level was attained within 44 h in 80% of
      the animals in the hMG-treated group, whereas in the FSH-treated group, the LH
      peak level tended to be reached later. The P4 level did not increase during the
      period of hMG or FSH treatment and decreased drastically following administration
      of PGF2alpha. After the onset of oestrus, the P4 level was higher in the hMG
      group than in the FSH group, and 5 to 7 days after oestrus, the level remained
      higher in the hMG group than in the FSH group (p < 0.05). After the first 3 days
      of hMG administration, the E2/P4 ratio was higher than that after FSH
      administration. Furthermore, on the day following PGF2alpha administration, the
      ratio was significantly higher in the hMG group than in the FSH group (p < 0.05).
      These results indicate that superovulation in cattle given hMG results in a
      significant increase in plasma E2 during the first 3 days and that the increase
      in the plasma P4 level is larger a few days after oestrus and thereafter compared
      with FSH-induced superovulation. Therefore, such plasma level profiles may be
      related to the increased recovery rate of high quality embryos.

PMID- 11328558
TI  - Hormonal response of female goats to active immunization against a recombinant
      human inhibin alpha-subunit, and establishment of an enzyme-linked immunosorbent
      assay for caprine follicle-stimulating hormone.
AB  - The effect of selective immunosuppression of endogenous inhibin in goats on FSH,
      LH, progesterone and estradiol-17beta profiles was studied during the breeding
      and nonbreeding seasons. Eighteen adult female Boer goats were immunized against
      the recombinant human inhibin alpha-subunit (hINH-alpha). With the exception of
      estradiol, which was determined by radio-immunoassay (RIA), all plasma hormone
      concentrations were determined by ELISA. The ELISA for FSH presented in this
      paper was established in the authors' laboratory, based on an existing RIA. Mean
      basal concentrations of FSH were not affected by immunosuppression of endogenous
      inhibin, nor was there a difference in the amplitude of the pre-ovulatory FSH
      surge. Immunization against inhibin appears to eliminate the slight secondary
      rise of FSH occurring 12-20 h after the major surge associated with ovulation.
      The LH profiles of the immunized goats were characterized by lower basal
      concentrations both before and after the pre-ovulatory LH surge which itself was
      reduced by 50% in immunized does. By contrast, concentrations of circulating
      estradiol were significantly elevated after inhibin-immunization. Progesterone
      profiles were not affected. Extending immunization into the anoestrous season by
      a booster injection of hINH-alpha, implicating oestrus induction with a
      progestagen and eCG, produced no discernible differences in FSH and LH profiles
      in comparison with nonimmunized control goats. The findings suggest that in
      goats, paracrine factors may play a more significant role in controlling
      follicular activity than a feedback mechanism acting via the pituitary.

PMID- 11328559
TI  - Differences in reproductive performance, embryo development, interferon-tau
      secretion by the conceptus and luteal function in ewe lambs synchronized in
      oestrus before or after the spontaneous onset of luteal activity preceding
      puberty.
AB  - In mid-September, 1 month before the insertion of intravaginal pessaries to
      induce sexual activity, blood samples were collected every 4 days from 16 ewe
      lambs aged 7 months, in order to determine the incidence of ovulations by
      measurement of plasma progesterone concentrations. It has been studied whether
      the response to a progestagen treatment of ewe lambs apparently close to puberty
      could be modified by the onset of the ovarian events preceding puberty. The
      effect of the presence or absence of ovulations prior to progestagen treatment on
      the potential reproductive performance (fertility, litter size and fecundity),
      embryo development [embryo quality and interferon-tau (IFNtau) secretion], luteal
      function (progesterone secretion in vitro) and endometrial progesterone content
      was studied in seven ovulating (Ov+) and nine nonovulating ewe lambs (Ov-) on day
      14 after mating. The best potential reproductive results were obtained with Ov+
      animals, although these differences could not be initially attributed to either
      different progesterone secretion in vitro or concentration of endometrial
      progesterone. Irrespective of the experimental groups, secretion of progesterone
      by luteal tissue from ewe lambs with normal embryos was significantly greater
      (p<0.05) than that of animals with abnormal embryos or with no embryos. Normal
      embryos secreted a higher amount of IFN-tau than those embryos classified as
      abnormal (p<0.07). In conclusion, ewe lambs which exhibit luteal activity before
      puberty have the highest levels of reproductive performances after a progestagen
      treatment. Corpora lutea from ewe lambs with normal embryos had higher rates of
      progesterone secretion in vitro and their embryos had a higher IFN-tau production
      by the embryos, indicating greater capacity for subsequent development.

PMID- 11328560
TI  - Evaluation of an artificial insemination programme in a seasonal breeding dairy
      system through milk progesterone.
AB  - In order to evaluate an artificial insemination programme and reproductive
      efficiency of dairy herds in Uruguay, a survey was conducted with five dairy
      farms, utilizing a total of 768 lactating Holstein cows. Precision of oestrous
      detection was assessed by one milk progesterone sample taken on day of breeding
      and was 11.1%. Two additional samples taken at day 10 and 23 were used to confirm
      ovulation and early pregnancy. Accuracy of pregnancy estimation by milk
      progesterone was 70.4%. Reproductive efficiency was determined by the analysis of
      records. Average intervals from calving to first service were 101 days and to
      conception 132 days and these were affected by parity, body weight and body
      condition at calving, but not at breeding, or by milk production. Oestrous
      detection rates and pregnancy rates were 37.5 and 15.6%, respectively. It was
      concluded that losses in reproductive efficiency in dairy farms of Uruguay in a
      seasonal artificial insemination programme were mainly due to unobserved heats,
      rather than incorrect oestrous detection.

PMID- 11328561
TI  - Factors affecting the reproductive efficiency of artificial insemination
      programmes in a seasonal breeding pasture-based dairy system with the aid of milk
      progesterone.
AB  - To determine the factors affecting reproductive efficiency in a seasonal breeding
      artificial insemination (AI) programme in dairy herds in Uruguay, a field trial
      was conducted on three dairy farms. Lactating cows (n=328) intended to be bred at
      the following breeding period were selected. The trial started 1 week before the
      beginning of the breeding period and lasted 80 days or until first service. Milk
      samples were obtained biweekly for 12 weeks, starting 1 week prior to the
      breeding season to determine progesterone concentrations. Data indicated that
      12.5% of the cows were anoestrus at the beginning of the season remaining in this
      condition throughout the trial. Most of the anoestrous animals were first-calf
      heifers. A varying number of cycling cows (8.5%) at each farm were never reported
      in heat. Oestrous detection rate for cows cycling, as determined by progesterone
      patterns, was evaluated in three periods of 21 days and resulted in an overall
      efficiency of 46.9%. Main factors affecting oestrous detection were farm, with an
      effect of parity (67.8%, mature cows and 33.2%, first-calf heifers) and no effect
      of days postpartum. Mean interval from the beginning of the breeding season to
      first breeding was 27.4 days, which was also affected by farm. Neither parity nor
      days postpartum affected this parameter.

PMID- 11328562
TI  - Assessment of sperm morphology in zebu bulls, under field conditions in the
      tropics.
AB  - Sperm morphology was studied in 302 extensively managed Zebu bulls (aged 1.5-9
      years), classified as sound (n=166) or unsound (n=136) for breeding, under field
      conditions in the dry tropics of Costa Rica. Single semen samples were collected
      by electro-ejaculation and fixed in formol-saline solution immediately after
      collection. Sperm morphology was determined in the field on wet smears using a
      microscope equipped with phase-contrast optics, and further determined in the
      laboratory on air-dried smears stained with carbol-fuchsin. The frequencies of
      sperm abnormalities (such as abnormal acrosome, head, neck, mid-piece, tail, and
      presence of cytoplasmic droplets) were recorded as a percentage of the total
      number of counted spermatozoa (400 cells). Zebu bulls considered unsound for
      breeding showed a higher mean prevalence (p < 0.05) of knobbed acrosomes (4.0
      versus 0.9%), head defects [specifically, nuclear invaginations and heads with
      abnormal shapes and sizes (27.6 versus 4.0%)], abnormal tails (11.2 versus 4.7%),
      and proximal droplets (8.4 versus 1.6%), compared with bulls considered sound for
      breeding. In these latter bulls, the abnormality most commonly seen was the
      presence of single bent tails with an entrapped cytoplasmic droplet (3.0 +/-
      3.7%). Young Zebu bulls (i.e. bulls under 2 years of age) showed a higher
      percentage of missing acrosomes, and proximal cytoplasmic droplets, than older
      sires (12.1 versus 2.4%, and 23.9 versus 3.6%, respectively; p < 0.05),
      interpreted as an indication of low ejaculation frequency and sexual immaturity,
      respectively. Bulls with a long scrotum and soft testicular consistency (TC) at
      palpation showed higher percentages of abnormal sperm heads in the ejaculate than
      bulls with a normal scrotal length (SL) and a normal TC (32.7 versus 12.8% and
      30.7 versus 10.3%, respectively; p < 0.05). In addition, Zebu bulls with a
      scrotal circumference (SC) < or = 30 cm showed a higher prevalence of proximal
      cytoplasmic droplets than bulls whose SC was > 30 cm (9.8 versus 2.6%, p < 0.05).
      A higher mean percentage of abnormally sized and shaped heads, especially
      undeveloped and narrow at the base, was more frequently found in stained smears
      than in unstained samples (26.0 versus 9.9%, p < 0.05), which clearly underlines
      the importance of using both stained and wet smears when assessing sperm head
      morphology. However, for a quick assessment of sperm morphology under field,
      tropical conditions, phase-contrast microscopy provides useful information for
      the spermiogramme evaluation.

PMID- 11328563
TI  - Active immunization against gonadotrophin-releasing hormone in Chinese male pigs.
AB  - We have investigated, under the normal conditions of local Chinese pig farming,
      castration of young male pigs by vaccination with a newly developed vaccine
      against gonadotrophin releasing hormone (GnRH). Because of the very early onset
      of puberty, long fattening period and relatively harsh circumstances in Chinese
      pig production, an investigation of the endocrine response of Chinese breeds to
      this type of vaccination was of particular interest. Fifteen crossbred boars
      (Yorkshire x Yanan) from three different litters were randomly assigned to three
      groups of five animals each. The first group was immunized at 13 weeks of age
      with a GnRH tandem dimer OVA-conjugate in Specol and received a booster
      immunization 8 weeks later. The second group was injected with Specol alone and
      served as untreated controls. The remaining group was surgically castrated at the
      time of weaning (at 6 weeks of age). Pigs were fed ad libitum from weaning
      onwards. All animals were slaughtered at 31 weeks of age. Immunized boars had
      undetectable or low serum testosterone (0.09 +/- 0.12 ng/ml), low fat
      androstenone (0.05 +/- 0.01 microg/g) levels and very low testes weights (19.1 +/
      4.3 g). Intact controls had much higher serum levels of testosterone (9.76 +/-
      4.81 ng/ml), fat androstenone levels (2.26 +/- 0.87 microg/g) and testes weights
      (114.3 +/- 29.41 g) at slaughter. Both the immunized and castrated group grew
      significantly faster than intact boars (p < 0.01). Average daily gains in
      immunized, castrated and intact animals were 0.69 +/- 0.08, 0.63 +/- 0.05 and
      0.42 +/- 0.07 kg (mean +/- SD), respectively. The present data demonstrate for
      the first time that the newly developed anti-GnRH vaccine works very well under
      practical Chinese pig farming conditions, and can be an attractive alternative to
      surgical castration.

PMID- 11328564
TI  - The content of beta-endorphin-like immunoreactivity in porcine corpus luteum and
      the potential roles of progesterone, oxytocin and prolactin in the regulation of
      beta-endorphin release from luteal cells in vitro.
AB  - The amount of beta-endorphin-like immunoreactivity (beta-END-LI) in porcine
      corpora lutea from several stages of the oestrous cycle and the effects of
      progesterone, oxytocin, and prolactin on beta-END-LI secretion in vitro by luteal
      cells were studied. Porcine corpora lutea obtained on days 1-5, 6-10, 11-13, 14
      18, and 19-21 of the cycle were used to prepare extracts for beta-END-LI
      determination. Additionally, corpora lutea from days 11-13 and 14-18 were
      enzymatically dissociated and isolated luteal cells were used for further study
      of beta-endorphin secretion in vitro. Cells were cultured in serum-free defined M
      199 medium (106 cells/ml) at 37 degrees C under 5% CO2 in air, for 12 h. The
      influences of the following factors on beta-END-LI secretion by luteal cells were
      tested: progesterone (10-9, 10-7 and 10-5 M), oxytocin (0.01, 0.1, 1 and 10
      ng/ml), and prolactin (0.1, 1, 10 and 100 ng/ml). The beta-END-LI contents in
      extracts and media were measured by radioimmunoassay. The tissue concentration of
      beta-END-LI was lowest on days 1-5 of the cycle (0.35 +/- 0.03 ng/g wet tissue).
      Subsequently, it constantly increased to the highest value on days 14-18 (16.58
      +/- 0.52 ng/g wet tissue) and on days 19-21 it declined (11.10 +/- 0.52 ng/g wet
      tissue). Progesterone at a low dose (10-9 M) resulted in significant (p < 0.05)
      increases and decreases in beta-END-LI secretion by luteal cells from days 11-13
      and 14-18, respectively. Higher doses of progesterone (10-7 and 10-5 M) had no
      effect on beta-END-LI release, compared with the control group. All dose-levels
      of oxytocin used decreased beta-END-LI secretion by luteal cells on days 11-13
      and 14-18 of the cycle. Prolactin at doses of 0.1 and 1 ng/ml on days 11-13, and
      all doses tested on days 14-18 resulted in decreases in beta-END-LI release from
      luteal cells. These results document evident changes in beta-END-LI content in
      the pig corpus luteum during its development and indicate the potential roles of
      progesterone, oxytocin, and prolactin in luteal cell secretion of beta-END-LI.

PMID- 11328566
TI  - Prion protein and developments in its detection.
AB  - The theoretical risk of transmission of variant Creutzfeldt-Jakob disease (vCJD)
      via blood transfusions has led to replacement of UK-derived plasma for
      fractionation by plasma sourced outwith the UK and the introduction of
      leucodepletion of donated blood and its components. Prion protein in an abnormal
      conformation (PrPsc) has been identified as inextricably linked with the
      infectivity of transmissible spongiform encephalopathies such as vCJD and in this
      review some of its properties relevant to its detection are considered. In
      particular its insolubility in nonionic detergents and its partial resistance to
      proteinase K digestion have provided methods for separating it from the normal
      abundant isoform PrPc prior to subsequent detection, usually by means of antibody
      probes. As yet no antibodies which discriminate between the abnormal and normal
      isoforms have been identified with the sole exception of one which is not
      suitable for generally used immunodetection systems. Most detection systems, such
      as immunohistochemistry or Western blotting, have been optimized for brain or
      lympho-reticular tissues. Much less information is available for assays applied
      to blood or plasma, although some recent publications provide indications of
      their feasibility. However, a number of obstacles remain to be overcome. These
      include the issues of assay validation, detection of extremely low levels of
      PrPsc in the presence of large excesses of PrPc, lack of available standardized
      reagents, assay specificity and practicality for large-scale screening use.
      Progress towards these goals is reviewed.

PMID- 11328567
TI  - Unchanging attitudes to autologous transfusion in the UK.
AB  - Our aim was to assess changes in attitudes to autologous transfusion amongst
      surgeons over a 10-year period in response to scientific evidence, public
      awareness, published guidelines, management and the increasing cost of blood
      products. Surgeons across the north-west of England completed questionnaires on
      knowledge, experience and attitude towards autologous transfusion in 1990, 1994
      and 1999. Main outcome measures were changes in knowledge, experience and
      utilization of autologous transfusion; perceived advantages of autologous
      transfusion, obstacles to its implementation in surgical practice and preferences
      for specific techniques (preoperative autologous donation, acute normovolaemic
      haemodilution, intraoperative and postoperative cell salvage). There has been
      little change in practice over 10 years. Many more surgeons were keen to employ
      autologous transfusion than were using it. Autologous transfusion was only used
      in general, orthopaedic and cardiothoracic surgery. Safety and patient preference
      were the main arguments for implementation and logistics the main obstacles.
      Autologous transfusion was used sporadically in surgical practice. Clinical
      trials are needed to guide clinicians in the choice of transfusion techniques.

PMID- 11328569
TI  - A potentially improved approach to methylene blue virus inactivation of plasma:
      the Maco Pharma Maco-Tronic system.
AB  - Plasma was subjected to methylene blue (MB) photochemical virus inactivation
      using the Maco Pharma Maco-Tronic system which allows three units to be
      illuminated together, thus reducing processing time. The plasma bag system used
      incorporates an integral membrane plasma filter and a dry MB pill which dissolves
      in the plasma to give a 1-microM concentration. There is computer-controlled
      processing and datalogging. In an assessment of 10 pools of Group A plasma, the
      losses of coagulation factors, following MB/light treatment, were 23% fibrinogen,
      10% FV, 26% FVIII, 11% FIX and 13% FXI. Group O, Group B and Group AB plasmas
      were not tested. Von Willebrand factor (vWf) multimers showed no substantial
      change when treated with MB, and no losses were seen for antithrombin III
      (ATIII), protein C and vWf:Ag. Measurements of C3a, C5a, prothrombin fragment 1+2
      and FXIIa indicated that there was no activation as a result of filtration.

PMID- 11328568
TI  - Expression of CD2 and activation markers on blood T-helper cell subsets in
      patients with transfusional iron overload.
AB  - The aim of the present study was to investigate the relationship between
      different measures of iron status, and the expression of CD2, and the activation
      markers CD25, CD71, CD45RO, HLADR CD38 within the Th-cell subset in patients with
      progressive transfusional iron overload. We estimated the expression of the
      activation surface markers on the Th cells of peripheral blood by flow cytometry
      from 22 multiply transfused patients. The number of CD2 binding sites (BS) on Th
      cells was significantly higher in the patients (82 917 +/- 30 801) than in age
      matched normal controls (41 145 +/- 6989, P < 0.0001). When investigating whether
      this difference could be due to the iron overload we found the number of CD2 BS
      closely related to the iron saturation of serum transferrin (TfS) (R2 = 0.78, P <
      0.001). The relationship to the serum ferritin concentration and to the number of
      blood units given was weaker, but also significant (R2 = 0.22, P < 0.027,
      respectively, R2 = 0.21, P < 0.032). Also the fraction of mature memory Th cells
      which express CD45RO at a high level was directly related to the TfS (R2 = 0.57,
      P < 0.0001), while the expression of CD38 within the Th cell fraction was
      inversely related to the TfS (R2 = - 0.43, P = 0.009). The expression of HLA-DR
      (but not of CD25 and CD71) was also directly related to the TfS (R2 = 0.29, P =
      0.01). Our results show a clear, statistical relationship between the iron status
      and the expression of surface markers within Th cells in multiply transfused
      patients.

PMID- 11328570
TI  - Vigam-S, a solvent/detergent-treated intravenous immunoglobulin, in idiopathic
      thrombocytopenic purpura.
AB  - The efficacy of Vigam-S, a highly purified intravenous immunoglobulin, was
      investigated by an open, noncomparative study in 20 adults with chronic
      idiopathic thrombocytopenic purpura (ITP). Fifteen patients responded to the
      initial 3-day infusion of 0.4 g kg(-1) day(-1) by exhibiting an incremental
      increase in platelet count of >or= 30 x 10(9) L(-1), in eight of whom platelet
      count normalized (> 150 x 10(9) L(-1)). The peak platelet count for responders on
      day 4 was 163 x 10(9) L(-1) (baseline = 18 x 10(9) L(-1)). No benefit was derived
      from an extra 2 days infusion in nonresponders. Further treatment (either a
      single 0.8 g kg(-1) dose or another 3-day infusion) given to responders when
      platelet counts fell below 30 x 10(9) L(-1) was effective on eight of 14
      occasions. Increases in total serum IgG concentration (to a mean peak of 25.3 g
      L(-1)) were not correlated with platelet response. There was no evidence of
      seroconversion to virus markers, or of alteration in renal function, following
      Vigam-S infusion. Most adverse events were mild and transient; however, three
      patients had severe headache and vomiting (possible aseptic meningitis syndrome)
      and one had marked superficial thrombophlebitis. Therefore Vigam-S provides
      effective and well tolerated therapy in the management of adults with ITP
      although individual patient response remains difficult to predict.

PMID- 11328571
TI  - Platelet washing to prevent recurrent febrile reactions to leucocyte-reduced
      transfusions.
AB  - Symptoms of fever and/or rigours after transfusion continue to occur commonly in
      patients receiving platelets leucocyte-reduced after storage. A cohort of 24
      consecutive patients who had experienced severe or repeated febrile nonhaemolytic
      reactions to post-storage leucocyte-reduced platelet transfusions were treated
      with saline-washed, post-storage leucocyte-reduced platelets. The frequency of
      reactions declined from 20% of transfusions (n = 191) to 0.6% (n = 331) after
      instituting saline-washed, post-storage leucocyte-reduced platelet transfusions.
      These results support the hypothesis that substances present in the supernatant
      of stored platelet concentrates mediate febrile nonhaemolytic transfusion
      reactions, and provide one strategy for preventing their occurrence.

PMID- 11328572
TI  - Variation of pH-measurement in platelet concentrates.
AB  - To measure pH in platelet concentrates, blood gas analysers with different
      calibration principles may be used. In this study, variances observed in pH
      measurements with two types of blood gas analysers were investigated. pH was
      measured in crystalloid solutions (platelet additive solution (PAS-II), phosphate
      buffered solutions) and two types of platelet concentrates (containing 100%
      plasma, or 65% PAS-II/35% plasma) with two blood gas analysers: either using
      liquid and gas calibration (AVL 945), or only liquid calibration (AVL OMNI).
      These measurements were compared with a reference method. Especially for PAS-II,
      large variation in pH was observed between AVL 945, AVL OMNI and the reference
      method: 6.91 +/- 0.02, 7.35 +/- 0.02 and 7.188 +/- 0.010, respectively (mean +/-
      SD; n = 12, P < 0.0001, paired t-test). A significant difference in pH was also
      found for platelet concentrates in 65% PAS/35% plasma (6.88 +/- 0.09 on AVL 945
      and 7.02 +/- 0.09 on AVL OMNI, n = 134, P < 0.0001). Comparison with the
      reference method revealed minor differences with AVL 945, whereas AVL OMNI gave a
      mean difference in pH of + 0.17. Platelets in 100% plasma revealed smaller
      differences (6.93 +/- 0.13 for AVL 945 and 6.99 +/- 0.13 for AVL OMNI, n = 95, P
      < 0.0001). We conclude that different blood gas analysers can yield different pH
      values, especially in weak buffered solutions such as platelet concentrates in
      PAS-II. Validation of blood gas analysers for pH measurement of these solutions
      is therefore mandatory.

PMID- 11328573
TI  - Refractory hyperhaemolysis in a patient with beta-thalassaemia major.
AB  - We report the case of a 1-year-old girl with newly diagnosed beta-thalassaemia
      major. Following an initial blood transfusion with phenotypically matched blood,
      she developed a haemolytic anaemia which progressed with subsequent transfusions.
      The Direct Antiglobulin test (DAT) was strongly positive with C3d and weakly with
      IgG. The only free antibodies detected were a weak anti-H and a weak cold auto
      antibody, which did not exhibit a wide thermal range. The indirect Donath
      Landsteiner and Ham's tests were negative. There was no sustained clinical
      response to steroids, immunoglobulin infusions or splenectomy. An HLA identical
      sibling donor was available for allogeneic bone marrow transplantation (BMT) and
      the haemolysis resolved during the immunosuppressive transplant conditioning.
      Such hyperhaemolysis without significant red cell alloantibodies has previously
      been reported in patients with sickle cell anaemia, but only rarely in patients
      with beta-thalassaemia major.

PMID- 11328574
TI  - Low ferritin levels indicate the need for iron supplementation: strategy to
      minimize iron depletion in regular blood donors.

PMID- 11328577
TI  - Xenotransplantation and the Council of Europe.

PMID- 11328578
TI  - Morphometric analysis of miniature swine hearts as potential human xenografts.
AB  - Miniature swine are considered to be potential donors for clinical cardiac
      transplantation. However, it is unclear how an appropriately sized porcine donor
      will be selected for a particular human recipient. To address this issue, we
      performed a morphometric study of the swine heart using transthoracic
      echocardiography (n = 26) to determine the diameters of the aortic annulus and
      root, pulmonary artery annulus, and mitral valve annulus. We also obtained direct
      ex vivo measurements of swine heart weight and linear dimensions (n = 71).
      Relationships between a swine's height, weight, length, chest circumference and
      these internal and external cardiac dimensions are described. The strongest
      correlations were found between a pig's body length and its aortic annulus and
      root diameters (r-values = 0.97). These relationships are accurately described by
      univariate linear regression models. By cross-relating our morphometric
      measurements of aortic annulus diameter in the miniature swine with normative
      human data, we were able to develop a nomogram, relating swine length and human
      height, which predicts which miniature swine would donate the best size-matched
      heart for a particular human recipient.

PMID- 11328579
TI  - Evaluation of a system for the perfusion of isolated, rodent organs.
AB  - Perfusion of isolated organs is a common experimental approach. However, the
      surfaces of the perfusion system might alter the components of the blood and
      thereby negatively affect organ function. The aim of this study was to minimize
      the influence of the perfusion system on the blood components and to evaluate the
      system. Pressure and flow in the perfusion system consisting of a roller-pump,
      reservoir, oxygenator, hemo-filter and bubble-trap with a total tubing length of
      4.5 m are controlled by a computer software (DASYLAB, Datalog, Moenchengladbach,
      Germany) via a transducer connected to the system. The organ to be perfused is
      positioned under a microscope (Orthoplan, Leica, Bensheim, Germany), allowing the
      investigation of microcirculatory parameters. The images raised are recorded on
      video tapes. To evaluate the system it was perfused with human blood (Hct 28 to
      30%) for 90 min. Heparin (n = 6) or citrate (n = 6) served as anti-coagulants.
      The disappearance of cells from the blood was determined at time points 0, 1, 5,
      10, 15, 20, 30, 45, 60, 75 and 90 min by means of a cell counter (AC T8, Coulter
      Beckmann, Krefeld, Germany). Cell activation was assessed by analysis of the
      expression of L- and P-selectin and CD11b. The activation of the complement
      system was examined by measuring the serum levels of the complement factors C3c
      and C4. There was no significant loss or activation of the blood cells at any of
      the above given time points. The serum levels of the complement factors remained
      within the physiological range and showed no changes throughout the whole
      experiments. Thus, the perfusion system does not have a negative influence on the
      blood and its individual components, and is therefore a reliable tool for
      perfusion experiments.

PMID- 11328580
TI  - Effect of cell surface concentration of human DAF on transgenic pig aortic
      endothelial cells on the degree of protection afforded against human complement
      deposition.
AB  - Cultures of hDAF transgenic porcine aortic endothelial cells (TPAEs) with levels
      of cell surface hDAF expression between 2000 and 300 000 molecules per cell have
      been used to determine the relationship between expression of hDAF and protection
      from human complement deposition in an in vitro model. At concentrations below 45
      000 molecules per cell, the relationship between hDAF expression and degree of
      protection conferred is linear. Concentrations of 123 000 molecules per cell and
      higher give maximal protection (60% reduction of susceptibility to neat human
      serum) in this model. It is concluded that increasing hDAF expression above that
      displayed by the A74 line of hDAF transgenic pigs (240 000 +/- 15 000 molecules
      per cell) would not confer any additional benefit.

PMID- 11328581
TI  - Differences between synthetic oligosaccharide immunoabsorbents in depletion
      capacity for xenoreactive anti-Galalpha1-3Gal antibodies from human serum.
AB  - Extracorporeal immunoabsorption for removal of anti-Galalpha1-3Gal (anti-Gal)
      antibodies in putative pig-to-human xenotransplantation is considered a major
      prophylactic measure to avoid hyperacute and acute vascular rejections. However,
      the efficacy of the procedure does depend on choosing the appropriate
      oligosaccharide epitopes for the binding of human anti-Gal. The synthetic
      oligosaccharides Galalpha1-3Gal (B-disaccharide, Bdi) and Galalpha1-3Galbeta1
      4Glc ('type 6' trisaccharide, Tri6), covalently coupled to Sepharose via
      polyacrylamide (Sorbents Bdi and -Tri6, respectively), as well as a mixture
      thereof (Sorbent Mix), were examined for their efficacy to absorb anti-Gal from
      20 human serum samples. Sorbent Bdi removed 81% of anti-Gal IgM and 85% of -IgG
      when assessed on Bdi by ELISA, but only 49% of IgG and 75% of IgM when assessed
      on Tri6. Sorbent Tri6 and -Mix showed significantly better absorption capacities
      in so far as Sorbent Tri6 removed 65% of anti-Gal IgM and 80% of -IgG as assessed
      on Bdi and 85% of IgM/87% of IgG when tested on Tri6, and Sorbent Mix absorbed >
      90% anti-Gal of both isotypes of either specificity. Direct hemagglutination of
      rabbit erythrocytes (ER) was reduced by 75% (median value, range 0-94%) and the
      median cytotoxicity to PK15 target cells by > 94% after absorption on Sorbent
      Mix. Neither the decrease in ER agglutination titers nor the reduction of PK15
      cytotoxicity revealed significant differences between the three immunoabsorbents
      tested. The large variation ranges of absorption efficacies within the 20 tested
      sera suggest that "tailor-made" immunoabsorption treatments may be needed for
      putative xenotransplant recipients.

PMID- 11328583
TI  - Sensitive and specific immunological detection methods for porcine endogenous
      retroviruses applicable to experimental and clinical xenotransplantation.
AB  - The use of organs from transgenic pigs for xenotransplantation may be associated
      with the risk of transmission of microorganisms, especially when the transgenic
      pigs express human proteins influencing complement activation. The porcine
      endogenous retroviruses (PERVs) are of particular concern as they can infect
      human cells in vitro. However, it is unknown whether PERVs can infect transplant
      recipients in vivo and, if so, whether they are pathogenic. It is therefore
      essential for experimental and clinical xenotransplantation procedures that
      specific and sensitive screening methods for PERVs are established. We developed
      Western blot and enzyme-linked immunosorbant assays (ELISA) based on purified
      PERVs produced by pig and human cells or recombinant viral protein and synthetic
      peptides corresponding to PERVs' transmembrane envelope protein, respectively.
      PERV-specific anti-sera generated against purified virus particles, purified
      viral proteins and synthetic peptides served as positive controls. Both assays
      were used for screening the sera of healthy blood donors, pregnant women,
      patients treated with pig tissues, and butchers with extensive contact to living
      porcine material to detect antibodies against PERV. None of the individuals
      showed an antibody pattern characteristic for retroviral infections. Some
      individuals had antibodies reactive against the major capsid protein p27, against
      smaller viral proteins of the group specific antigen (Gag) in Western blot
      assays, or against peptides in the ELISA, probably due to cross-reactivity. Here,
      we present specific and highly sensitive screening methods applicable for future
      xenotransplantation procedures, but using these methods we found no evidence of
      PERV-infection among humans potentially at risk.

PMID- 11328582
TI  - In vitro prevention of cell-mediated xeno-graft rejection via the Fas/FasL
      pathway in CrmA-transducted porcine kidney cells.
AB  - Cell-mediated cytotoxicity may be involved in delayed and/or chronic xenograft
      rejection in which apoptosis is induced in the grafted cells via the Fas/Fas
      ligand (FasL) and perforin/granzyme pathways. One barrier to the potential use of
      xeonogenic grafts for humans may be Fas/FasL-mediated apoptosis, which would be
      blocked by the gene expression of cytokine response modifier A (CrmA), a cowpox
      virus gene product. The purpose of this study is to explore whether crmA is an
      effective candidate gene for inhibiting apoptosis in an in vitro model of
      xenograft rejection, using Fas-expressing non-primate cells cultured with a
      soluble recombinant human FasL (sFasL). A recombinant adenovirus vector
      expressing CrmA (AxCALNLCrmA) was successfully generated with a Cre-mediated
      switching system. PK15 cells, derived from a porcine kidney and infected with
      AxCALNLCrmA and/or AxCANCre at a multiplicity of infection (MOI) ranging from 0.1
      to 100, were cultured with human sFasL derived from KFL74.18, a human FasL
      overexpressed cell line. The gene-expression level of the PK15 cells was
      confirmed by CrmA-immune staining. Approximately 70% of the control PK15 cells
      showed induced apoptosis when cultured with sFasL. In contrast, the apoptosis was
      dramatically reduced in crmA-gene-transduced PK15 cells. The inhibitory effect of
      apoptosis increased with an increase in the infection dose of AxCANCre. In
      addition, the activity of caspases 3 and 8 was significantly inhibited in the
      crmA-transduced cells. These results indicate that CrmA is an effective gene
      product for inhibiting Fas/FasL-mediated apoptosis, which suggests the potential
      therapeutic use of its gene transduction to protect against graft damage due to
      delayed and/or chronic xenograft rejection.

PMID- 11328584
TI  - Different mechanisms mediate the rejection of porcine neurons and endothelial
      cells transplanted into the rat brain.
AB  - In order to investigate the early cellular responses mediating xenograft
      rejection in the brain, porcine aortic endothelial cells (PAEC) or porcine fetal
      mesencephalic neurons (PNEU) were transplanted into the striatum of LEW.1A rats.
      PAEC were detected with a specific anti-beta1 integrin antibody, and PNEU with an
      anti-porcine neurofilament antibody, or an antibody recognizing the NeuN antigen.
      PAEC grafts were massively infiltrated within 24 h by OX42-positive cells, which
      may correspond to polymorphonuclear (PMN) cells or macrophages. At that moment,
      the graft contained numerous cells expressing the inducible isoform of NO
      synthase (iNOS). Infiltration by ED1-positive macrophages was effective after
      three days. The beta1-integrin labeling decreased from that time-point to day 7
      post-implantation, and vanished after 11 days. Although some OX8-positive cells
      were present around the graft as soon as 3 days after transplantation, cells
      expressing the T-cell receptor (TCR)-beta chain infiltrated the graft after 7
      days and their number remained low. A strong, diffuse OX8-and ED1-positive
      immunoreactive material remained in the scar up to the third week. In striking
      contrast, PNEU grafts remained poorly infiltrated by OX42- or ED1-positive cells
      during the first two weeks. A massive infiltration by macrophages and TCRbeta
      positive lymphocytes occurred after 3 weeks. Natural killer (NK) cells were more
      scarce. The inflammation territory enlarged, and blood vessels were overloaded
      with macrophages or lymphocytes. Nevertheless, the graft contained NeuN-positive
      nuclei and neurites harbouring the porcine neurofilament protein. Hence,
      rejection was not completed at this time-point. These results suggest that the
      rapid rejection of PAEC is mainly driven by macrophages and possibly PMN cells,
      unlike PNEU, whose rejection is delayed and also involves lymphocytes.
      Differences in immunogenicity of grafted cells and/or patterns of production of
      pro-inflammatory cytokines may account for these contrasted rejection kinetics.

PMID- 11328585
TI  - The structure of calpain.
AB  - Recent very rapid developments in genome and EST projects have identified an
      increasing number of gene products homologous to those that were previously
      identified by other methods. Calpain is no exception. At the time this review is
      written, 83 genes from 23 living organisms have been identified in the database
      to encode amino acid sequences showing significant similarities to the protease
      domain of "conventional" calpain, which was first purified as a homogeneous
      protein in 1978. Progress in genome/EST projects has occurred so quickly that
      there seems to be some confusion as to the identity of each calpain molecule.
      This review will attempt to clarify all calpain homologues, to describe the
      common and differing features of calpain homologues in terms of structure
      function relationship, and to discuss the evolutionary process of calpain.

PMID- 11328586
TI  - Activation by 2-arachidonoylglycerol, an endogenous cannabinoid receptor ligand,
      of p42/44 mitogen-activated protein kinase in HL-60 cells.
AB  - 2-Arachidonoylglycerol (2-AG), an endogenous cannabinoid receptor ligand, was
      shown to induce rapid phosphorylation of p42/44 mitogen-activated protein kinase
      (MAP kinase) in HL-60 cells. We confirmed that the enzyme activity of p42/44 MAP
      kinase in HL-60 cells was augmented markedly when the cells were stimulated with
      2-AG. The addition of SR144528, a cannabinoid CB2 receptor-specific antagonist,
      to the cells prior to the addition of 2-AG abolished the response induced by 2
      AG, indicating that the CB2 receptor is involved in the response. G protein G(i)
      or G(o) is also assumed to be involved, because pertussis toxin treatment of the
      cells nullified the response induced by 2-AG. CP55940 and anandamide also induced
      the activation of p42/44 MAP kinase, although the activation by anandamide was
      less pronounced than that by 2-AG or CP55940. These results suggest that 2-AG may
      play an important physiological role in this type of cell through the activation
      of the p42/44 MAP kinase cascade.

PMID- 11328588
TI  - Alkaline-resistance model of subtilisin ALP I, a novel alkaline subtilisin.
AB  - The alkaline-resistance mechanism of the alkaline-stable enzymes is not yet
      known. To clarify the mechanism of alkaline-resistance of alkaline subtilisin,
      structural changes of two typical subtilisins, subtilisin ALP I (ALP I) and
      subtilisin Sendai (Sendai), were studied by means of physicochemical methods.
      Subtilisin NAT (NAT), which exhibits no alkaline resistance, was examined as a
      control. ALP I gradually lost its activity, accompanied by protein degradation,
      but, on the contrary, Sendai was stable under alkaline conditions. CD spectral
      measurements at neutral and alkaline pH indicated no apparent differences between
      ALP I and Sendai. A significant difference was observed on measurement of
      fluorescence emission spectra of the tryptophan residues of ALP I that were
      exposed on the enzyme surface. The fluorescence intensity of ALP I was greatly
      reduced under alkaline conditions; moreover, the reduction was reversed when
      alkaline-treated ALP I was neutralized. The fluorescence spectrum of Sendai
      remained unchanged. The enzymatic and optical activities of NAT were lost at high
      pH, indicating a lack of functional and structural stability in an alkaline
      environment. Judging from these results, the alkaline resistance is closely
      related to the surface structure of the enzyme molecule.

PMID- 11328587
TI  - Use of bleomycin- and heat shock-induced calreticulin promoter for construction
      of a mammalian expression vector.
AB  - Addition of bleomycin (Bm) to an NIH/3T3 cell culture induced the overproduction
      of four cellular proteins [Kumagai and Sugiyama (1998) J. Biochem. 124, 835-841].
      The two proteins were identified on N-terminal amino acid sequence analysis as
      calreticulin and mitochondrial matrix protein P1, which are known as heat shock
      proteins, respectively. In this study, we cloned the calreticulin promoter region
      from the genomic DNA of NIH/3T3 cells and observed that heat shock treatment at
      42 degrees C or the addition of Bm to the cell culture caused overexpression of
      the luciferase gene controlled by the cloned calreticulin promoter. This suggests
      that Bm induces the transcriptional activation of stress-heat shock genes. We
      constructed an expression vector for mammalian cells, which is controlled by the
      calreticulin promoter.

PMID- 11328589
TI  - Effects of deoxycholic acid and its epimers on lipid peroxidation in isolated rat
      hepatocytes.
AB  - We studied the effects of deoxycholic acid and its three epimers with beta
      hydroxyl groups (3alpha,12beta-, 3beta,12alpha-, and 3beta,12beta-dihydroxy-5beta
      cholan-24-oic acids), which were hydrophilic and less cytotoxic, on lipid
      peroxidation to elucidate the relationship between structural features of bile
      acids and their effect on lipid peroxidation. Taurodeoxycholate markedly
      increased the production of thiobarbituric acid-reactive substances, end products
      of lipid peroxidation, in isolated rat hepatocytes, whereas epimers of
      taurodeoxycholate did not. Deoxycholic acid inhibited mitochondrial NADH
      dehydrogenase and NADH:ferricytochrome c oxidoreductase activities, leading to
      free radical generation, whereas epimers of deoxycholic acid had no effect on
      mitochondrial enzymes. These findings suggested that hydrophobic bile acids cause
      lipid peroxidation by impairment of mitochondrial function, leading to the
      generation of free radicals; and epimerization of alpha-hydroxyl groups in the
      steroid nucleus to beta-hydroxyl groups results in a decrease of the toxic
      effects of deoxycholic acid on lipid peroxidation.

PMID- 11328590
TI  - Localization of neuronal growth-associated, microtubule-destabilizing factor
      SCG10 in brain-derived raft membrane microdomains.
AB  - Raft is a mobile membrane subdomain enriched in sphingolipid and cholesterol and
      also various signaling molecules. Previous observation suggested that brain
      derived rafts contain tubulin but that rafts of non-neural origin do not. We
      hypothesized that SCG10, one of the neuronal growth-associated proteins (nGAPs),
      might be a neuron-specific molecule that anchors tubulin to neuronal rafts, and
      we explored biochemically its subcellular localization, interaction with tubulin,
      and effects on microtubule dynamics. In postnatal rat brain extracts, SCG10 was
      recovered mostly in membrane-associated fractions, and at least half was included
      in the raft fraction that was also enriched in GAP-43 and NAP-22. SCG10-enriched
      brain rafts also contained tubulin, and chemical cross-linking experiments
      revealed that SCG10 was closely associated with tubulin. In addition, SCG10 was
      able to inhibit polymerization of tubulin. These results indicate that SCG10 is a
      component of neuronal rafts as are other nGAPs, and suggest that SCG10 may be
      involved in signaling events in membranes for cytoskeletal reorganization around
      neuronal rafts.

PMID- 11328591
TI  - The human homologue of fission Yeast cdc27, p66, is a component of active human
      DNA polymerase delta.
AB  - An essential eukaryotic DNA polymerase, DNA polymerase delta (pol delta),
      synthesizes DNA processively in the presence of proliferating cell nuclear
      antigen (PCNA). Recently, a 66 kDa polypeptide (p66) that displays significant
      homology within its PCNA binding domain to that of fission yeast cdc27 was
      identified as a component of mouse and calf thymus pol delta. Our studies show
      that p66 interacts tightly with other subunits of pol delta during size
      fractionation of human cell extracts, and co-immunoprecipitates with these
      subunits along with PCNA-dependent polymerase activity. Active human pol delta
      could be reconstituted by co-expressing p125, p50, and p66 recombinant
      baculoviruses, but not by co-expressing p125 and p50 alone. Interaction studies
      demonstrated that p66 stabilizes the association between p125 and p50. Pull-down
      assays with PCNA-linked beads demonstrated that p66 increases the overall
      affinity of pol delta for PCNA. These results indicate that p66 is a functionally
      important subunit of human pol delta that stabilizes the pol delta complex and
      increases the affinity of pol delta for PCNA.

PMID- 11328592
TI  - Characterization of cytochrome b(5) in the ascidian Polyandrocarpa misakiensis
      and budding-specific expression.
AB  - A cDNA for cytochrome b(5) was cloned from a cDNA library of buds of the
      ascidian, Polyandrocarpa misakiensis, by a hybridization method involving a
      digoxigenin-labeled cDNA probe of human soluble cytochrome b(5). The nucleotide
      sequence of the cDNA for the ascidian cytochrome b(5) (Pmb5) consisted of about
      1,800 base pairs including 5'- and 3'-noncoding regions, and a coding sequence of
      405 base pairs. The amino acid sequence of 135 residues deduced from the coding
      nucleotide sequence exhibited 54% identity and 76% similarity to chicken
      cytochrome b(5). A highly conserved amino acid sequence was observed in the amino
      terminal domain of 96 residues containing two heme-binding histidine residues.
      The putative soluble form of the recombinant Pmb5 expressed in Escherichia coli
      was purified to homogeneity by column chromatographies on an anion-exchanger and
      gel filtration. The purified Pmb5 showed the typical absorption spectrum of
      cytochrome b(5) with an asymmetric peak at 556 nm and a shoulder at 560 nm upon
      reduction with NADH and NADH-cytochrome b(5) reductase. The low temperature
      spectrum of the dithionite-reduced form of the protein contained the split peaks
      at 551 and 555 nm, this spectrum being very similar to that of mammalian liver
      cytochrome b(5). Expression of Pmb5 in the ascidian was examined
      immunohistochemically with a monoclonal antibody against the Pmb5. Apparently
      high level expression of Pmb5 was found in the developing buds, but the levels of
      cytochrome b(5) in the parents and juvenile adults were very low. This is the
      first report on the characterization of Pmb5, and the increased expression of
      Pmb5 in the ascidian.

PMID- 11328593
TI  - Effects of recombinant human macrophage colony-stimulating factor on
      atherosclerotic lesions established in the aorta of high cholesterol-fed rabbits.
AB  - Anti-atherosclerotic effects of human macrophage colony-stimulating factor were
      investigated using rabbits fed a high cholesterol diet. Rabbits fed a diet
      containing 2% cholesterol for 59 days developed hyperlipidemia and atheromatous
      aortic plaques. They were then administered 80 microg/kg/day of either macrophage
      colony-stimulating factor or human serum albumin, as a control, for the next 12
      weeks. Compared with the control group, rabbits treated with macrophage colony
      stimulating factor had significantly fewer plaques on the inner surface of the
      thoracic and abdominal aortae, and half the sectional area of thickened intima in
      the aortic arch, as well as in the thoracic and abdominal aortae. Macrophage
      colony-stimulating factor also decreased the cholesterol content of the
      atherosclerotic lesions. Serobiochemical analyses revealed that macrophage colony
      stimulating factor increased the levels of high density lipoprotein-cholesterol
      significantly, without influencing other lipid parameters such as the level of
      low density lipoproteins. The effects of macrophage colony-stimulating factor
      were evident until the fourth week of drug injection, at which time anti-human
      macrophage colony-stimulating factor antibodies were clearly induced in the
      serum. These results indicate that exogenously administered macrophage colony
      stimulating factor suppresses atherosclerotic lesions induced by a high
      cholesterol diet by activating lipid metabolism in vivo.

PMID- 11328594
TI  - Effect of aggregation of amphotericin B on lysophosphatidylcholine micelles as
      related to its complex formation with cholesterol or ergosterol.
AB  - The effect of aggregation of amphotericin B (AmB), as well as the complex
      formation of AmB with cholesterol or ergosterol, was investigated in micelles and
      vesicles. AmB in lysophosphatidylcholine (LPC) micelles adopted a more favorable
      monomeric form than that in other drug formulations. At an LPC/AmB ratio of 200,
      AmB existed only in monomeric form. Such monomeric behavior is likely dependent
      upon the fluidity and size of the micelles. In LPC micelles composed of 90%
      monomeric AmB, AmB-ergosterol complex formation occurred with an increase in the
      sterol concentration, but the complex formation of AmB-cholesterol was slight. On
      the other hand, in LPC micelles composed of 40% monomeric AmB, the complex
      formation of AmB-cholesterol as well as AmB-ergosterol was extensive. These
      results suggest that the complex formation of AmB with both sterols is highly
      dependent upon the aggregated state of AmB. In addition, using monolayers,
      mixtures of AmB/LPC/ergosterol were became more stable with rising temperature,
      while the stability of mixtures of AmB/LPC/cholesterol remained unchanged,
      implying that complex formation of AmB with cholesterol is different from that of
      AmB with ergosterol.

PMID- 11328595
TI  - Differential control of cellular gene expression by diffusible and non-diffusible
      EGF.
AB  - Cell gene expression is affected by both the kind and mode of growth factor
      stimulation (diffusive vs. non-diffusive). Epidermal growth factor (EGF) was
      pattern-immobilized on a polystyrene plate. Although the growth of the rat
      phaeochromocytoma cell line PC12 is stimulated by diffusible EGF, and
      differentiation is stimulated by diffusible nerve growth factor (NGF),
      immobilized (non-diffusible) EGF stimulated PC12 differentiation. The immobilized
      EGF caused a long-lasting stimulation of the intracellular signal protein mitogen
      associated protein MAP kinase (MAPK, also known as ERK) and p38 (a subfamily of
      the MAPK superfamily) in cells, as did diffusible NGF. The switching between
      growth stimulation and differentiation is considered to be due to the duration of
      the stimulus. The function of the biosignal conjugate was regulated using
      conjugation methodology.

PMID- 11328596
TI  - Dynamics of intracellular granules with CD63-GFP in rat basophilic leukemia
      cells.
AB  - CD63 is located on the basophilic granule membranes in resting basophils, mast
      cells, and platelets, and is also located on the plasma membranes of the cells.
      We constructed a CD63-GFP (green fluorescent protein) plasmid and introduced it
      into rat basophilic leukemia (RBL-2H3) cells to observe the movements of CD63 on
      degranulation. The movements of CD63-GFP were studied in living RBL cells by
      confocal laser scanning microscopy (CLSM). CD63-GFP, in which GFP was conjugated
      to the C-terminus of CD63, was located on both the granule membranes and the
      plasma membranes of RBL cells. The diameter of the fluorescent granules in the
      cytoplasm varied from 0.5 to 1.5 microm. Before antigen stimulation most granules
      with CD63-GFP hardly moved in RBL cells. However, after antigen stimulation the
      plasma membranes ruffled violently and the granules moved dramatically. They
      reached the plasma membranes in a few minutes and fused with them
      instantaneously. Analysis of the movement of each granule provided a new insight
      into the elementary process of degranulation. The velocity of the granule
      movement toward the plasma membranes on antigen stimulation was calculated to be
      0.1+/-0.02 microm/s. This shows that the granules are able to reach the plasma
      membranes in 2 or 3 min if the diameter of the cells is 20 microm.

PMID- 11328597
TI  - Substrate specificity of Ca(2+)/calmodulin-dependent protein kinase phosphatase:
      kinetic studies using synthetic phosphopeptides as model substrates.
AB  - Ca(2+)/calmodulin-dependent protein kinase phosphatase (CaMKPase)
      dephosphorylates and regulates multifunctional Ca(2+)/calmodulin-dependent
      protein kinases. In order to elucidate the mechanism of substrate recognition by
      CaMKPase, we chemically synthesized a variety of phosphopeptide analogs and
      carried out kinetic analysis using them as CaMKPase substrates. This is the first
      report using systematically synthesized phosphopeptides as substrates for kinetic
      studies on substrate specificities of protein Ser/Thr phosphatases. CaMKPase was
      shown to be a protein Ser/Thr phosphatase having a strong preference for a
      phospho-Thr residue. A Pro residue adjacent to the dephosphorylation site on the
      C-terminal side and acidic clusters around the dephosphorylation site had
      detrimental effects on dephosphorylation by CaMKPase. Deletion analysis of a
      model substrate peptide revealed that the minimal length of the substrate peptide
      was only 2 to 3 amino acid residues including the dephosphorylation site. The
      residues on the C-terminal side of the dephosphorylation site were not essential
      for dephosphorylation, whereas the residue adjacent to the dephosphorylation site
      on the N-terminal side was essential. Ala-scanning analysis suggested that
      CaMKPase did not recognize a specific motif around the dephosphorylation site.
      Myosin light chain phosphorylated by protein kinase C and Erk2 phosphorylated by
      MEK1 were poor substrates for CaMKPase, while a synthetic phosphopeptide
      corresponding to the sequence around the phosphorylation site of the former was
      not dephosphorylated by CaMKPase but that of the latter was fairly good
      substrate. These data suggest that substrate specificity of CaMKPase is
      determined by higher-order structure of the substrate protein rather than by the
      primary structure around its dephosphorylation site. Use of phosphopeptide
      substrates also revealed that poly-L-lysine, an activator for CaMKPase, activated
      the enzyme mainly through increase in the V(max) values.

PMID- 11328598
TI  - Efficient transfer of intact oligonucleotides into the nucleus of ligament scar
      fibroblasts by HVJ-cationic liposomes is correlated with effective antisense gene
      inhibition.
AB  - The efficacy of two different cationic liposomes, Lipofectin and hemagglutinating
      virus of Japan (HVJ)-cationic liposomes, on nuclear uptake of fluorescence
      labeled phosphorothioate oligodeoxyribonucleotide (S-ODN) by ligament scar
      fibroblasts and suppression of decorin mRNA expression when antisense decorin S
      ODN was transferred was investigated. There was no significant difference in
      nuclear uptake of fluorescent ODN between the two methods. However, only HVJ
      cationic liposomes had a significant effect on suppression of decorin mRNA
      expression levels. To address the discrepancy, the molecular integrity of the
      transferred ODN in the cells was assessed by analysis of fluorescence resonance
      energy transfer (FRET) within double-fluorescence-labeled S-ODN. More than 70% of
      the ODN transfected by HVJ-cationic liposomes remained intact within the nucleus
      at 20 h after transfection, while the majority of the ODN transferred by
      Lipofectin was degraded at this point. These results suggest a strong
      relationship between the nuclear integrity of transfected antisense ODN and its
      suppression of target mRNA expression.

PMID- 11328599
TI  - The amino acid residues affecting the activity and azole susceptibility of rat
      CYP51 (sterol 14-demethylase P450).
AB  - The amino acid residues affecting the function of rat sterol 14-demethylase P450
      (CYP51) were examined by means of point mutation. Forty-five mutants with respect
      to 27 amino acid sites were constructed and expressed in Escherichia coli.
      Substitution of highly conserved Y131, E369, R372, or R382 decreased the
      expression of CYP51 protein, indicating some structural importance of these
      residues. Substitution of H314, T315, or S316 caused considerable effects on the
      catalytic activity, and T315 was identified as the "conserved threonine" of
      CYP51. H314 was important for maintenance of the activity of CYP51 and was a
      characteristic residue of this P450, because the position corresponding to this
      residue is occupied by an acidic amino acid in most other P450 species. A144 was
      identified as a residue affecting the interaction of CYP51 with ketoconazole.
      Substitution of A144 with I, which occupies the corresponding position in fungal
      CYP51, enhanced the ketoconazole susceptibility of rat CYP51 with little change
      in the catalytic activity, indicating an important role of this residue in
      determination of the ketoconazole susceptibility of CYP51. Alteration of the
      catalytic activity was caused by the substitution at some other sites, whereas
      substitution of a few highly conserved amino acids caused little alteration of
      the activity of CYP51.

PMID- 11328600
TI  - New gene cluster for lantibiotic streptin possibly involved in streptolysin S
      formation.
AB  - Streptolysin S (SLS) is a serum-extractable and oxygen-stable hemolysin produced
      by Group A Streptococcus. A SLS-deficient mutant in which transposon Tn 916 was
      inserted in a locus distinct from the sag gene cluster [Nizet et al. (2000)
      Infect. Immun. 68, 4245-4254] was obtained by filter mating of the transposon
      harbouring Enterococcus faecalis strain and Streptococcus pyogenes BL(T). This
      mutant, N22, had completely lost the hemolytic activity, in consequence of
      insertion of a single Tn 916 into a hitherto-unknown lantibiotic gene cluster
      composed of 10 open reading frames. The arrangement and sequence of this
      lantibiotic gene cluster were similar to those of nisin and subtilin, and so we
      designated this new lantibiotic as streptin. The bactericidal activity of
      streptin was abolished on treatment with trypsin or proteinase K. The different
      host range and nucleotide sequence clearly distinguished streptin from
      streptococcins. Streptin was not hemolytic and its bacteriocin activity was
      independent of carrier oligonucleotides effective for SLS. The fact that N22 also
      lost the anti-bacterial activity against indicator streptococci reveals that the
      factor(s) required for lantibiotic formation plays an important role in SLS
      formation as well.

PMID- 11328601
TI  - Ancestral residues stabilizing 3-isopropylmalate dehydrogenase of an extreme
      thermophile: experimental evidence supporting the thermophilic common ancestor
      hypothesis.
AB  - Ancestral amino acid residues were inferred for 3-isopropylmalate dehydrogenase
      (IPMDH), and were introduced into the enzyme of an extreme thermophile,
      Sulfolobus sp. strain 7. The thermostability of the mutant enzymes was compared
      with that of the wild type enzyme. At least five of the seven mutants tested
      showed higher thermal stability than the wild type IPMDH. The results are
      compatible with the hyperthermophilic universal ancestor hypothesis. The results
      also provide a new method for designing thermostable enzymes. The method only
      relies on the first dimensional structures of homologous enzymes that can be
      obtained from genetic databases.

PMID- 11328602
TI  - Cyclic and linear peptides derived from alpha-amylase inhibitory protein
      tendamistat.
AB  - Tendamistat is a strong inhibitory protein of porcine pancreatic alpha-amylase
      (PPA) with a K(i) value of 0.2 nM. To develop potent alpha-amylase inhibitors, we
      synthesized six odd-length cyclic peptides (5-15 residues) and four even-length
      cyclic peptides (10 and 12 residues) having the inhibitory sequence of
      tendamistat. Their PPA inhibitory activities were evaluated, and, among them, the
      11-residue cyclic peptide Ten(15-23) (K(i) = 0.27 microM) exhibited the strongest
      inhibitory activity (K(i) = 0.27-1.41 microM). To examine the effect of cyclic
      structure on PPA inhibition, ten linear peptides corresponding to the cyclic
      peptides were also synthesized, and their PPA inhibitory activities were
      evaluated (K(i) = 0.28-1.00 microM). Interestingly, the 11-residue linear peptide
      Ten(15-23) exhibited almost the same inhibitory activity (K(i) = 0.28 microM) as
      that of cyclic Ten(15-23). The results of a circular dichroism study indicated
      that stabilization of the beta-hairpin structure occurred only for cyclic Ten(15
      23). Also, the results of proteolytic digestion experiments of the cyclic and
      linear Ten(15-23) peptides by trypsin and chymotrypsin suggested no differences
      in protease resistance between the cyclic and linear structures. Therefore, we
      demonstrated that both cyclic and linear peptides containing the inhibitory
      sequence of tendamistat exhibit potent PPA inhibitory activity.

PMID- 11328603
TI  - Replacements of amino acid residues at subsites and their effects on the
      catalytic properties of Rhizomucor pusillus pepsin, an aspartic proteinase from
      Rhizomucor pusillus.
AB  - Site-directed mutagenesis was carried out to investigate the functional roles of
      amino acid residues of Rhizomucor pusillus pepsin (RMPP) in substrate-binding and
      catalysis. Mutations of two amino acid residues, E13 in the S3 subsite and N219
      in the S3/S4 subsites, caused marked changes in kinetic parameters for two
      substrate peptides with different sequences. Further site-directed mutagenesis at
      E13 suggested that E13 plays a critical role in forming the correct hydrogen bond
      network around the active center. In the crystal structure of Rhizomucor miehei
      pepsin (RMMP), which is an aspartic proteinase produced by Rhizomucor miehei and
      shows 81% amino acid identity to RMPP, the Oepsilon atom of N219 forms a hydrogen
      bond with the N-H of isovaline in pepstatin A, a statine-type inhibitor, at the
      P3 position, suggesting that the loss of the hydrogen bond causes an unfavorable
      arrangement of the P3 residue. Among the mutants constructed, the E13A mutant
      showed a 5-fold increase in the ratio of clotting versus proteolytic activity
      without significant loss of clotting activity. This mutant may present a
      promising candidate for a useful milk coagulant.

PMID- 11328604
TI  - A synthetic dDAF (CD55) gene based on optimal codon usage for transgenic animals.
AB  - The human DAF (CD55) gene was chosen as a representative molecule in a
      xenotransplantation study. The gene was synthesized in order to adapt its codons
      to those which are more frequent in mammals, especially pigs, and the expression
      levels were then examined in Chinese hamster ovarian (CHO) cells, swine
      endothelial cell (SEC) and transgenic mice. A significant increase in protein
      production with no detectable mRNA elevation was observed in the transfectants of
      synthetic DAF (sDAF), compared with the wild-type DAF (wtDAF) and delta-SCR1 wild
      type DAF (Delta1wtDAF). Consistent with the in vitro data, the expression of DAF
      in mice that carry sDAF was higher than Delta1wtDAF in many organs, especially
      the pancreas. The sDAF showed a high level of expression in SEC and transgenic
      mice, suggesting that it will be useful in the development of transgenic pigs
      with high levels of expression.

PMID- 11328605
TI  - Roles of N-terminal active cysteines and C-terminal cysteine-selenocysteine in
      the catalytic mechanism of mammalian thioredoxin reductase.
AB  - Mammalian thioredoxin reductase [EC 1.6.4.5], a homodimeric flavoprotein, has a
      marked similarity to glutathione reductase. The two cysteines in the N-terminal
      FAD domain (-Cys59-x-x-x-x-Cys64-) and histidine (His472) are conserved between
      them at corresponding positions, but the mammalian thioredoxin reductase contains
      a C-terminal extension of selenocysteine (Sec or U) at the penultimate position
      and a preceding cysteine (-Gly-Cys497-Sec498-Gly). Introduction of mutations into
      the cloned rat thioredoxin reductase gene revealed that residues Cys59, Cys64,
      His472, Cys497, and Sec498, as well as the sequence of Cys497 and Sec498 were
      essential for thioredoxin-reducing activity. To analyze the catalytic mechanism
      of the mammalian thioredoxin reductase, the wild-type, U498C, U498S, C59S, and
      C64S were overproduced in a baculovirus/insect cell system and purified. The wild
      type thioredoxin reductase produced in this system, designated as WT, was found
      to lack the Sec residue and to terminate at Cys497. A Sec-containing thioredoxin
      reductase, which was purified from COS-1 cells transfected with the wild-type
      cDNA, was designated as SecWT and was used as an authentic enzyme. Among mutant
      enzymes, only U498C retained a slight thioredoxin-reducing activity at about
      three orders magnitude lower than SecWT. WT, U498C, and U498S showed some 5,5'
      dithiobis(2-nitrobenzoic acid)-reducing activity and transhydrogenase activity,
      and C59S and C64S had substantially no such activities. These data and spectral
      analyses of these enzymes suggest that Cys59 and Cys64 at the N-terminus, in
      conjunction with His472, function as primary acceptors for electrons from NADPH
      via FAD, and that the electrons are then transferred to Cys497-Sec498 at the C
      terminus for the reduction of oxidized thioredoxin in the mammalian thioredoxin
      reductase.

PMID- 11328607
TI  - Only the reduced conformer of alpha-lactalbumin is inducible to aggregation by
      protein aggregates.
AB  - Reduced apo-alpha-lactalbumin (r-LA) in the pre-molten globule state is soluble
      in neutral and reduced buffer at 25 degrees C but becomes aggregated when
      aggregates of various proteins are added. However, protein aggregates do not
      induce the aggregation of apo-alpha-lactalbumin in the molten globule state. The
      presence of the molecular chaperone protein disulfide isomerase or the "chemical
      chaperone" polyethyleneglycol inhibits the induced aggregation. Native proteins,
      aggregation-free folding intermediates, and soluble aggregates do not induce the
      aggregation. The interaction between r-LA and protein aggregates is hydrophobic
      in nature. These findings suggest that pre-molten globule state of LA is the
      target not only for chaperones but also for protein aggregates.

PMID- 11328606
TI  - Heat shock factor 2 is involved in the upregulation of alphaB-crystallin by high
      extracellular potassium.
AB  - alphaB-Crystallin, a member of the small heat shock protein (HSP) family,
      accumulates in reactive astrocytes in a variety of pathological conditions. We
      previously reported the upregulation of alphaB-crystallin in response to high
      extracellular potassium concentration. In the present study, we investigated the
      regulatory mechanism of alphaB-crystallin expression by KCl. When human glioma U
      251MG cells were exposed to continuous KCl treatment, induction of alphaB
      crystallin mRNA was observed after 8 h and persisted for a few days. Functional
      promoter analysis using deletion and mutation constructs revealed that the
      proximal heat shock element (HSE-P), which contributes to heat shock induction in
      HeLa cells, is essential for transcriptional activation of the alphaB-crystallin
      gene by KCl in U-251MG cells. Gel mobility shift and antibody supershift assays
      showed that KCl induces the HSE-binding activity of heat shock factor (HSF) 2,
      while heat shock induces that of HSF1. This is the first demonstration that HSF2
      can be activated by KCl and is involved in the upregulation of alphaB-crystallin
      gene expression in glial cells.

PMID- 11328608
TI  - Characterization of a Saccharomyces cerevisiae gene that encodes a mitochondrial
      phosphate transporter-like protein.
AB  - The mitochondrial phosphate transporter of Saccharomyces cerevisiae, encoded by
      MIR1 (YJR077C) gene, shows divergence among the transporters in various
      eukaryotes. We have characterized another gene, YER053C, that appeared to encode
      an orthologous mitochondrial phosphate transporter of yeast. The predicted amino
      acid sequence of the YER053C protein is much more similar to that of
      mitochondrial phosphate transporters of other species than that of MIR1. RNA gel
      blot analysis indicated that, like the MIR1 promoter, the YER053C promoter is
      functional and that its activity varies according to aeration. An MIR1 gene null
      mutant did not grow on glycerol medium, whereas a YER053C null mutant grew well
      on the medium, suggesting that the YER053C gene is not essential for the
      mitochondrial function. YER053C also did not support the growth of the MIR1 null
      mutant on glycerol. The MIR1 and YER053C proteins were expressed in Escherichia
      coli and then reconstituted into liposomes. Unlike the proteoliposomes of MIR1,
      those of YER053C did not exhibit significant phosphate transport activity.
      Unexpectedly, it was shown that YER053C is localized in vacuoles, not
      mitochondria, by immunological electron microscopy. These results suggest that,
      during evolution, yeast lost the function and/or mitochondrial targeting of
      YER053C and then recruited an atypical MIR1 as the only transporter.

PMID- 11328609
TI  - Ca(2+)- and myristoylation-dependent association of calcineurin with
      phosphatidylserine.
AB  - It has been proposed that N-terminal myristoylation of calcineurin B is necessary
      for the membrane association of calcineurin. We tested the effects of Ca(2+) and
      myristoylation on the binding of calcineurin B alone or heterodimeric calcineurin
      to phosphatidylserine or phosphatidylcholine vesicles. In the presence of excess
      phosphatidylserine, 50-60% of total calcineurin associated with
      phosphatidylserine in a Ca(2+)-sensitive manner. Calcineurin did not associate
      with phosphatidylcholine. Calcineurin containing both the alpha and beta
      catalytic subunit isoforms bound to phosphatidylserine. Calmodulin interfered
      with the association of calcineurin with phosphatidylserine. In the presence of
      Ca(2+), myristoylated calcineurin B alone did not bind to phosphatidylcholine but
      did bind to phosphatidylserine, although to a lesser extent than the calcineurin
      heterodimer. Non-myristoylated calcineurin B alone, or calcineurin containing non
      myristoylated calcineurin B did not associate with phosphatidylserine in the
      presence of Ca(2+). These results indicate: (i) Both isoforms of calcineurin bind
      to phosphatidylserine. (ii) A phospholipid binding site is located on the
      calcineurin B subunit. (iii) Calcineurin B myristoylation is required for the
      Ca(2+)-sensitive binding of calcineurin to phosphatidylserine vesicles in vitro.

PMID- 11328610
TI  - A cluster of basic amino acid residues in calcineurin b participates in the
      binding of calcineurin to phosphatidylserine vesicles.
AB  - Interactions between phospholipid membranes and the acyl chain and specific amino
      acid residues of myristoylated proteins are necessary for membrane association.
      In the present study we tested the effects of mutations of calcineurin B subunit
      amino acid residues K(20)K(21), K(24)R(25), K(27)K(28) to Glu on the interactions
      between calcineurin and phosphatidylserine vesicles. Calcineurin
      phosphatidylserine interactions were measured using binding assays and assays of
      phosphatidylserine-stimulated calcineurin phosphatase activity. The reverse
      charge calcineurin B subunit mutant had a slower mobility in SDS-PAGE relative to
      wild-type calcineurin B. In addition, the myristoylated calcineurin B reverse
      charge mutant had a slower mobility in SDS-PAGE compared to the non-myristoylated
      form, in contrast to the faster mobility of myristoylated wild-type calcineurin B
      relative to non-myristoylated calcineurin B. The reverse-charge mutations had no
      apparent effect on N-terminal myristoylation, Ca(2+)-binding, or calcineurin
      heterodimer formation and stimulation of Ca(2+)/calmodulin-dependent phosphatase
      activity. However, in contrast to the results obtained using native calcineurin,
      phosphatidylserine vesicles did not bind to or activate the phosphatase activity
      of calcineurin containing the calcineurin B reverse-charge mutant. These results
      indicate that calcineurin B contains an amino terminal basic residue cluster that
      is involved in the binding of calcineurin to acidic phospholipids.

PMID- 11328611
TI  - Acanthosis nigricans in obese patients: Presentations and implications for
      prevention of atherosclerotic vascular disease.
AB  - Acanthosis nigricans is traditionally characterized by hyperpigmented, velvety
      plaques of body folds. Involvement of other areas occurs as well. The condition
      is caused by hyperinsulinemia, a consequence of insulin resistance that occurs
      associated with obesity. As the frequency and degree of obesity increase in the
      population, a concomitant increase in acanthosis nigricans can be expected. The
      dermatologist has an important role in identifying the subset of obese patients
      with acanthosis nigricans. These patients have hyperinsulinemia and may be at
      greater risk of consequent atherosclerotic cardiovascular disease. It is
      essential for dermatologists to recognize the many presentations of acanthosis
      nigricans to identify patients at risk for associated medical conditions. This
      article illustrates a variety of presentations of acanthosis nigricans associated
      with insulin resistance.

PMID- 11328612
TI  - The Ultraviolet Index: a useful tool.
AB  - The Ultraviolet Index was developed in the United States in 1994 following
      successful use of ultraviolet (UV) alerts in other countries. This daily National
      Weather Service prediction is a calculation which integrates five data elements
      to yield the amount of UV radiation impacting the surface (1m2) at solar noon in
      58 of the largest US population centers. This simple numeric prediction is then
      categorized by the Environmental Protection Agency into five "exposure levels"
      with protective actions recommended for each level. This information is
      disseminated through the media. Daily reminders seem to affect awareness and
      behavior in Canada, but US surveys indicate the need for better understanding
      through educational graphics. Comparing the UV Index to a precipitation
      prediction has merit in that it links a familiar daily prediction with implied
      appropriate protective measures. Graphics link the ideas that "when it rains it
      pours and when it shines it radiates." Beginning in schools, camps, and
      dermatology meetings, using the rain/shine analogy, a wider exposure to the
      Ultraviolet Index is proposed.

PMID- 11328613
TI  - A review of topical and intralesional cidofovir.
AB  - Cidofovir is a potent nucleoside analog antiviral drug approved for the treatment
      of cytomegalovirus (CMV) retinitis in patients with the Acquired Immune
      Deficiency Syndrome (AIDS). It is currently available only for intravenous
      infusion. Several small studies and case reports describe the successful use of
      cidofovir applied either topically or by intralesional injection in several
      virally induced cutaneous diseases. Available information demonstrates that
      cidofovir is a potent antiviral agent with activity against several DNA viruses
      that cause cutaneous disease when applied topically or administered by
      intralesional injection. No significant systemic side effects have been noted,
      although application site reactions are common and can occasionally be severe.
      The effective use of topical and intralesional cidofovir for the treatment of
      diseases of the skin caused by DNA viruses has been demonstrated in animals and a
      limited number of patients including those infected with human immunodeficiency
      virus (HIV). This article reviews the pharmacology of cidofovir and the utility
      of topical and intralesional cidofovir for the treatment of viral infections
      caused by human papillomavirus, herpesviruses (including acyclovir resistant
      strains), Kaposi's sarcoma-associated herpesvirus, molluscum contagiosum and
      monkeypox.

PMID- 11328614
TI  - Advances in psoriasis treatment.
AB  - Psoriasis is a complex disorder that negatively impacts quality of life.
      Treatment strategies must address both psychosocial and physical aspects of the
      disease. Psoriasis can be categorized into localized and generalized forms for
      treatment purposes. In either case, the treatment plan should include obtaining
      rapid control of the disease and maintaining that control. For localized disease,
      recent data support the combined use of topical corticosteroids with a
      noncorticosteroid agent (topical calcipotriene or tazarotene). For generalized
      disease, UVB phototherapy is an effective treatment that permits both rapid
      control and long-term maintenance. Use of low doses of acitretin (25mg qd or qod)
      potentiates both UVB and PUVA therapy. For patients unresponsive to phototherapy
      or who are not able to come on a regular basis, methotrexate is an effective
      alternative. Cyclosporine is useful, especially for short-term use in settings of
      acute exacerbation, but should be replaced by other modalities for long-term
      maintenance. Other agents that have a place in treatment of generalized psoriasis
      include hydroxyurea and mycophenolate mofetil.

PMID- 11328616
TI  - Telangiectasia macularis eruptiva perstans.

PMID- 11328615
TI  - Melanoma vaccines.
AB  - Melanoma vaccines are the best near term hope for improving mortality in patients
      with advanced disease. Although these vaccines are being developed for treatment
      of patients with advanced disease, their relatively low toxicity make them
      attractive for adjuvant therapy in stage I patients at high risk for recurrence.
      Recent developments in melanoma vaccines are reviewed and their importance to
      dermatologists is emphasized.

PMID- 11328618
TI  - Cutaneous endometriosis.

PMID- 11328617
TI  - Familial benign pemphigus.

PMID- 11328619
TI  - Lepromatous leprosy with drug reaction.

PMID- 11328620
TI  - Steatocystoma multiplex.

PMID- 11328621
TI  - Cutaneous horn present for two months.

PMID- 11328622
TI  - Basal cell carcinoma (BCC) causing spinal cord compression.
AB  - Basal cell carcinoma (BCC) is the most common cutaneous malignancy affecting
      populations with light skin, though these tumors rarely cause severe morbidity or
      mortality. We report an adult male with back pain and leg weakness associated
      with a neglected, ulcerated lower back tumor of fifteen years duration. The
      clinical impression of BCC causing spinal cord compression was confirmed by
      microscopy and magnetic resonance imaging (MRI).

PMID- 11328623
TI  - Current treatment of cutaneous lupus erythematosus.
AB  - Cutaneous lupus erythematosus has a variety of clinical presentations, but
      treatment is similar for the different forms. The antimalarials remain the
      cornerstone of treatment because of their effectiveness and safety. Optimal use
      of the antimalarials as well as alternative therapy options are discussed.

PMID- 11328624
TI  - Current treatment of Cutaneous T-Cell Lymphoma.
AB  - Cutaneous T-cell lymphomas are a heterogeneous group of cutaneous non-Hodgkin's
      lymphomas. In the United States, the incidence of these diseases is rising faster
      than any other cancer. Environmental triggers may be important in the evolution
      of malignancy. Current therapy is reviewed with emphasis on a new retinoid,
      Targretin.

PMID- 11328625
TI  - Keratosis lichenoides chronica: report of a new case, with success of PUVA
      therapy.
AB  - Keratosis lichenoides chronica is a rare disorder. It consists of the progressive
      development of asymptomatic verrucosities on the limbs and the trunk, with a
      partially linear distribution. We report the case of a 78-year-old woman who
      presented with keratotic plaques and papules of the trunk and the limbs for
      several years. A diagnosis of keratosis lichenoides chronica was clinically and
      histologically evident. PUVA-therapy was started, with excellent results.

PMID- 11328626
TI  - Lichen planus of the eyelids. A report of 5 cases.
AB  - Involvement of the eye and related structures is rarely reported in lichen
      planus. Only eleven cases with eyelid involvement are reported in the literature.
      Lesions on the eyelids may be the only manifestation of lichen planus or it may
      be a part of the disease process present on other parts of the body. When only
      eyelids are involved, clinical diagnosis may be difficult. Lichen planus should
      be considered in the differential diagnosis of erythematous papular lesions on
      the eyelids.

PMID- 11328627
TI  - Kissing bugs (Triatoma) and the skin.
AB  - Kissing bugs (Family Reduviidae) can be the source of nocturnal dermatologic
      wounds in the mid to southern latitudes in the United States. The insects are
      obligate blood feeders and though the bites may be asymptomatic, a variety of
      dermatologic eruptions or death from anaphylaxis can result. The various
      dermatologic forms of the bite can be mistaken for herpes zoster, erythema
      multiforme and the ubiquitous catch-all diagnoses of "spider-bite."

PMID- 11328628
TI  - A brief history of the Department of Dermatology, New York University.

PMID- 11328629
TI  - Acquired Blaschko dermatitis.

PMID- 11328630
TI  - Allergic contact dermatitis to textile dyes.

PMID- 11328631
TI  - Focal acral hyperkeratosis.

PMID- 11328632
TI  - Psoriatic onycho-pachydermo-periostitis.

PMID- 11328633
TI  - Tinea capitis.

PMID- 11328634
TI  - Confluent and reticulate papillomatosis.

PMID- 11328635
TI  - Epidermal nevus.

PMID- 11328636
TI  - Mid-dermal elastolysis.

PMID- 11328637
TI  - Scleroderma.

PMID- 11328638
TI  - Polyarteritis nodosa.

PMID- 11328639
TI  - Pretibial myxedema.

PMID- 11328640
TI  - Lividoid vasculitis.

PMID- 11328641
TI  - An open label safety study of topical imiquimod 5% cream in the treatment of
      Molluscum contagiosum in children.
AB  - The objective of this study was to evaluate the safety of imiquimod 5% cream, a
      potent inducer of interferons, in children with molluscum contagiosum. The
      lesions of thirteen subjects (mean age 7 years) were treated every night for 4
      weeks. A visual analog scale was used to assess any adverse local skin reactions,
      and for the presence of systemic side effects characteristic of interferon (IFN).
      Temperature and total white blood cell count were measured at baseline and
      compared with results at weeks 2 and 4. In the twelve subjects who completed the
      study, adverse reactions were limited to application site reactions. We did not
      find any evidence of systemic toxicity. In conclusion, imiquimod 5% cream appears
      to be a safe treatment in children with molluscum contagiosum.

PMID- 11328642
TI  - A 2D finite element model of the interventricular septum under normal and
      abnormal loading.
AB  - The interventricular septum is the structure that separates the left and right
      ventricles of the heart. Under normal loading conditions, it is concave to the
      left ventricle, but under abnormal loading the septum flattens and occasionally
      inverts. In the past, the septum has frequently been modelled as integral to the
      left ventricle with the effects of pressure from the right ventricle being
      ignored. Under abnormal loading, the septum has been described as behaving
      equivalent to a "flapping sail". There has been no consideration of structural
      behaviour under these conditions. A 2-D plane stress FE model of the septum was
      used to investigate the difference in structural behaviour of the septum during
      diastole between normal and abnormal loading. The biaxial stress patterns that
      develop are distinctively disparate. Under normal loading, the septum behaves
      much like a thick-walled cylinder subject to internal and external pressure, with
      the resulting stresses being circumferential tension and radial compression, both
      varying with radius. These stresses are very low throughout most of diastole.
      However, under abnormal loading, the septum behaves in an arch-like fashion, with
      high compressive stresses almost circumferential in direction, combined with
      radial compression. We conclude that right ventricular pressures cause bending
      effects in the wall of the heart, and that under abnormal loading, the
      compressive stresses that develop in the septum may lead to an understanding of
      certain, previously unexplained, pathological conditions.

PMID- 11328643
TI  - Numerical models for the simulation of flexible artificial heart valves: part I-
      computational methods.
AB  - A numerical model of the coupled motion of a flexing surface in a high Reynolds
      number flow is presented for the simulation of flexible polyurethane heart valves
      in the aortic position. This is achieved by matching a Lagrangian dynamic leaflet
      model with a panel method based flow solver. The two models are coupled via the
      time-dependent pressure field using the unsteady Bernoulli equation.
      Incorporation of sub-cycling in the dynamic model equations and fast pre
      conditioning techniques in the panel method solver yields efficient convergence
      and near real-time simulations of valve motion. The generality of dynamic model
      allows different material properties and/or geometries to be studied easily and
      interactively. This interactivity is realized by embedding the models within a
      design environment created using the software IRIS Explorer. Two flow domains are
      developed, an infinite domain and an internal domain using conformal mapping
      theory. In addition bending stress on the valve is computed using a simple stress
      model based on spline and circle equation techniques.

PMID- 11328644
TI  - An investigation into the feasibility of implementing fractal paradigms to
      simulate cancellous bone structure.
AB  - Cancellous bone consists of a framework of solid trabeculae interspersed with
      bone marrow. The structure of the bone tissue framework is highly convoluted and
      complex, being fractal and statistically self-similar over a limited range of
      magnifications. To date, the structure of natural cancellous bone tissue has been
      defined using 2D and 3D imaging, with no facility to modify and control the
      structure. The potential of four computer-generated paradigms has been reviewed
      based upon knowledge of other fractal structures and chaotic systems, namely
      Diffusion Limited Aggregation (DLA), Percolation and Epidemics, Cellular
      Automata, and a regular Grid with randomly relocated nodes. The resulting
      structures were compared for their ability to create realistic structures of
      cancellous bone rather than reflecting growth and form processes. Although the
      creation of realistic computer-generated cancellous bone structures is difficult,
      it should not be impossible. Future work considering the combination of fractal
      and chaotic paradigms is underway.

PMID- 11328645
TI  - An anisotropic internal-external bone adaptation model based on a combination of
      CAO and continuum damage mechanics technologies.
AB  - In this work, a complete internal-external bone-remodelling scheme is presented
      and implemented into a finite element code. This model uses a combination of an
      anisotropic internal remodelling model based on a new Continuum "Damage-Repair"
      theory and an external adaptation approach that follows the idea, early
      introduced by Mattheck et al., to simulate the growth behaviour of biological
      systems, known as CAO method. This combined scheme qualitatively resembles most
      of the main features of the bone adaptive behaviour, like the bone mass
      distribution (heterogeneity and porosity), the directional internal structure
      (anisotropy), the alignment of the microstructure with the constitutive principal
      directions and these with those of the stress tensor when permanently loaded by a
      unique stress state (Wolff's law). It is also thermodynamically consistent,
      fulfilling a principle of minimum mechanical dissipation. Finally, the comparison
      between the predicted results and the ones obtained by different experimental
      tests allows us to conclude that this model is able of reproducing qualitatively
      the global behaviour of bone tissue when subjected to external mechanical loads.

PMID- 11328646
TI  - Complete genomic sequence of 195 Kb of human DNA containing the gene GABRG2.
AB  - GABA (gamma-aminobutyric acid), as the main inhibitory neurotransmitter in the
      brain, plays an essential role for the overall balance between neuronal
      excitation and inhibition by acting on GABAA receptors, which are ligand-gated
      chloride channels. Impaired GABAergic function contributes to certain forms of
      epilepsy, schizophrenia, Alzheimer's Disease, and other neurological disorders.
      In order to identify possible genetic features and to further study biological
      regulation of GABAA receptor genes whose promoter elements and sequence anomalies
      may contribute to epileptic disorders, as an initial step, we shot-gun sequenced
      a BAC clone, dj082c10 (195,909-bp in size), encompassing human gamma(2) subunit
      of GABAA receptor (GABRG2). It is, we believe, the first genomic sequence of the
      GABA receptor gamma subunit family. Four contigs were assembled from 2950 reads
      prior to gap in an average redundancy of eight folds over the entire region. The
      precision of the consensus sequence was predicted to be 99.999% after closing
      gaps and finishing weak regions. The nine exons of GABRG2 spans an 85-kb region
      that had 81 SINEs comprising 22.32%, and nine L1 elements comprising 3.40%,
      respectively. However, the density of L1 in the regions flanking GABRG2 gene
      (29.45% by 45 elements) is significantly higher than that within the gene. The
      length of GABRG2 introns varies in the range of 1.5 kb to 38.1 kb.

PMID- 11328647
TI  - Structure of the urease operon of Corynebacterium glutamicum.
AB  - Urease activity of Corynebacterium glutamicum results in a rapid pH increase upon
      addition of urea to the growth medium. The urease operon C. glutamicum was
      isolated of and sequenced. Seven open reading frames were identified; ureA, ureB,
      and ureC were homologues of other bacterial urease structural genes, ureE, ureF,
      ureG, and ureD exhibited homology to urease accessory genes. Disruption of ureC
      prevented the utilization of urea as a nitrogen source by C. glutamicum. Urease
      activity was induced by urea and appeared to be independent of the nitrogen
      regulatory system. Urease activity was not affected by pH. Heterologous
      expression of a truncated derivative of the urease gene cluster in Escherichia
      coli showed that ureD was necessary for active expression. Western-blot and
      primer extension analysis on C. glutamicum grown under different conditions
      confirmed that the operon was induced by urea. Transcriptional startpoint for the
      ureA gene was determined.

PMID- 11328648
TI  - Identification and characterization of the gene encoding the mitochondrial
      elongation factor G in rice.
AB  - A plant nuclear gene coding for a mitochondrial elongation factor G (mEF-G) was
      cloned from a cDNA library and genomic library of rice (Oryza sativa L.). This
      DNA sequence predicts a 757-amino-acid protein exhibiting 79%, 55% and 49%
      homology to Arabidopsis thaliana, Saccharomyces cerevisiae and rat mEF-G
      respectively, 53% homology to the elongation factor G in Escherichia coli and 43%
      homology to soybean chloroplast elongation factor G. The deduced amino acid
      sequence contains the characteristic motifs shared by all GTP binding proteins.
      Comparison of the sequence of the genomic clone to that of the cDNA clone
      revealed that this gene is split nineteen times by introns, although the gene of
      Arabidopsis is split seventeen times by introns. Some of the introns found in the
      rice genome are relatively long and they result in a long gene with a size of
      approximately 15 kb.

PMID- 11328649
TI  - cDNA sequence and genomic structure of the rat RET proto-oncogene.
AB  - The RET proto-oncogene, a member of the Receptor Tyrosine Kinase family, plays a
      crucial role during the development of the excretory system and the enteric
      nervous system, as demonstrated by in vivo animal studies and by its involvement
      in the pathogenesis of several human neurocristopathies like Hirschsprung disease
      and Multiple Endocrine Neoplasia type 2. Using a multistep RT-PCR approach we
      have isolated and sequenced the cDNA of the whole rat RET proto-oncogene,
      reporting the deduced amino acid sequence in comparison with the human and mouse
      counterparts. Moreover, two different isoforms (RET9 and RET51) have been
      confirmed in the rat, while a third RET isoform demonstrated in human (RET43) has
      not resulted to be conserved in this species. Finally, we have determined the
      genomic structure of the rat RET proto-oncogene comparing the exon-intron
      boundaries and intron sizes with the known structure of the human homologous
      gene. Our findings will facilitate the molecular study of appropriate rat models
      of RET related human diseases.

PMID- 11328650
TI  - MglA and mglB of Treponema denticola; similarity to ABC transport and spa genes.
AB  - The mglA and mglB genes (td-mglA and td-mglB) of the oral spirochete Treponema
      denticola were sequenced. These two T. denticola genes are highly homologous to
      the E. coli and Treponema pallidum mglA and mglB genes which are part of the
      three gene beta-methylgalactoside transport operon, mglBAC. Both Td-mglA and td
      mglB are also homologous to the high affinity ABC-type transporters for ribose
      and arabinose, and surface presentation antigens (spa) locus, part of the type
      III secretion systems in enteropathogens. Td-mglB and td-mglA are co-transcribed
      as a single mRNA in T. denticola as well as in E. coli cells as determined by
      reverse transcription PCR (RT-PCR). Homology to td-mglB and its expressed protein
      was found in other oral spirochetes as determined by Southern and western blot
      analysis.

PMID- 11328651
TI  - Vg1 orthology in the direct developing frog, Syrrhophus cystignathoides campi.
AB  - Syrrhophus cystignathoides campi is a direct developing frog species that matures
      without passing through a larval (tadpole) stage. We have cloned and sequenced
      the Syrrhophus cDNA orthologous to the Xenopus Vg1 cDNA. The Syrrhophus Vg1
      (sVg1) cDNA spans 1323 nucleotides and encodes a predicted protein of 345 amino
      acids which is 81% identical at its carboxyl terminal end to Xenopus Vg1. In
      addition, it contains seven conserved cysteine residues present in all Vg1
      related proteins. Despite this high degree of similarity it is apparently missing
      a conserved N-linked glycosylation site and has an altered proteolytic processing
      sequence. Interestingly it is also missing a nine nucleotide sequence in its 3'
      UTR believed to be important for mRNA localization in Xenopus and Drosophila.
      These sequence variations could alter the functional expression and localization
      of the protein.

PMID- 11328652
TI  - Cloning and sequencing of the rabbit FGFR2 cDNA.

PMID- 11328653
TI  - Short sequence repeat polymorphism in the mouse slc4al gene encoding the AE1 Cl
      /HCO3-exchanger.
AB  - The human AE1 anion exchanger gene SLC4A1 encodes the Cl-/HCO3-exchangers of the
      erythrocyte and the Type Acid-secreting intercalated cell basolateral membrane.
      Mutations in SLC4A1 have been correspondingly linked with autosomal dominant
      hereditary spherocytotic anemia and with both dominant and recessive forms of
      distal renal tubular acidosis. Murine knockouts in the slc4a1Ae1 gene have also
      been generated, and lack erythroid and renal expression. However, intragenic
      polymorphic markers for the slc4a1 gene have been unavailable. Here we report
      that a previously identified CA repeat element of intron 13 of the murine Ae1
      gene exhibits strain-specific length polymorphism.

PMID- 11328654
TI  - Molecular cloning and complete cDNA sequences of the ribosomal proteins rpl34 and
      rpl44 from Aedes triseriatus mosquitoes.
AB  - We present the complete cDNA and deduced amino acid sequences of the 60S
      ribosomal subunit proteins, rpL34 and rpL44, from Aedes triseriatus mosquitoes.
      The rpL34 cDNA is 554 nucleotides in length and encodes a 139 amino acid protein
      with a calculated molecular mass of 15 732 daltons. The putative protein displays
      strong sequence similarity to rpL34 of Aedes albopictus mosquitoes (92%), humans
      (60%) and rats (58%). The protein is highly basic and contains a C-terminal
      repetitive-alanine domain and four putative nucleolar localization signals. The
      rpL44 cDNA consists of 450 nucleotides and encodes a 104 amino acid protein with
      a calculated molecular mass of 12 544 daltons. The putative protein displays
      strong sequence similarity to rpL44 of Brugia malayi (87%), Caenorhabditis
      elegans (86%) and humans (85%). The protein is highly basic and contains a
      putative nucleolar localization signal. The mRNAs for both rpL34 and rpL44 were
      detected in biosynthetically active (embryonating) and dormant (diapausing) Ae.
      triseriatus embryos by RT-PCR analysis.

PMID- 11328655
TI  - POU genes in metazoans: homologs in sea anemones, snails, and earthworms.
AB  - Previously undescribed POU genes were detected in several invertebrate phyla
      using redundant primers in a polymerase chain reaction (PCR) that targeted highly
      conserved sequences encoding known POU-domains. A class IV gene and a gene
      tentatively assigned to class VI were identified in sea anemones (Condylactis),
      two distinct class III genes were identified in snails (Biomphalaria), and a
      single class IV gene was identified in earthworms (Lumbricus). The identification
      of POU genes in cnidarians, mollusks, and annelids completes a survey of the
      major metozoan phyla. As POU genes exist in all of these organisms, they appear
      to be a fundamental characteristic of the metazoan lineage, and may have played a
      major role in the diversification of these organisms.

PMID- 11328656
TI  - Polynucleotide: adenosine glycosidase activity of immunotoxins containing
      ribosome-inactivating proteins.
AB  - Polynucleotide:adenosine glycosidases (rRNA N-glycosidases, EC 3.2.2.22, more
      commonly known as ribosome-inactivating proteins, RIP) are a numerous family of
      plant and bacterial enzymes, shown to release also adenine from DNA in vitro.
      They are well suited for the preparation of specifically toxic conjugates with
      several carriers, including monoclonal antibodies (immunotoxins). Here we show
      that (i) immunotoxins containing various PNAG (dianthin, gelonin, momordin I, PAP
      S, PDS-2, ricin A-chain, saporin-L1, saporin-S6) all act on DNA; (ii) activity on
      DNA in vitro is less compromised by disulphide linkage to antibody than is
      inhibition of cell-free protein translation; and (iii) specific cytotoxicity of
      immunotoxin does not correlate with substrate specificity.

PMID- 11328657
TI  - Distribution of albumin nanoparticles in animals induced with the experimental
      allergic encephalomyelitis.
AB  - Experimental allergic encephalomyelitis (EAE) is an autoimmune disease
      characterised by a disruption of the blood-brain barrier (BBB), demyelination and
      a relevant inflammatory reaction with an intense infiltration of macrophages.
      These neurological disorders are similar to those observed in the multiple
      sclerosis (MS) disease. The use of different liposomes and adeno-associated virus
      has been proposed for improving the treatment of this pathogenesis. The aim of
      this work was to evaluate the potential and capacity of albumin nanoparticles to
      reach the central nervous system (CNS) in EAE-induced rats. For this purpose, the
      distribution of biotinylated nanoparticles within the CNS was studied. Albumin
      carriers were mainly found in the lumbar portion of the spinal cord, overlying
      the meningeal and perivascular areas. The optic chiasma, iris and the area of the
      Purkinje cells of the cerebellum revealed also an intense presence of these
      carriers. Finally, immunohistochemical studies also revealed that circulating
      macrophages (ED1), which migrate to damaged sites, and resident activated
      microglial cells (OX42) were involved in the distribution of albumin
      nanoparticles. In summary, the use of nanoparticles may be useful for the design
      of new pharmaceutical dosage forms able to target the lesions associated with
      alterations of the BBB.

PMID- 11328658
TI  - In vitro and in vivo efficacy of acid-sensitive transferrin and albumin
      doxorubicin conjugates in a human xenograft panel and in the MDA-MB-435 mamma
      carcinoma model.
AB  - Acid-sensitive transferrin and albumin conjugates with doxorubicin have recently
      been developed with the aim of circumventing the systemic toxicity and improving
      the therapeutic efficacy of this anticancer agent. The in vitro activity of two
      acid-sensitive transferrin and albumin doxorubicin conjugates and free
      doxorubicin was evaluated in twelve human tumour xenografts using a clonogenic
      assay. The inhibitory effects and the activity profile of the conjugates was, in
      general, comparable to that of doxorubicin (mean IC(70) -value for doxorubicin
      approximately 0.1 microM and 0.1 - 0.4 microM for the conjugates). Subsequently,
      the efficacy of an acid-sensitive transferrin and albumin doxorubicin conjugate,
      which both incorporated a phenylacetyl hydrazone bond as a predetermined breaking
      point, was evaluated in the xenograft mamma carcinoma model MDA-MB-435 in
      comparison to free doxorubicin (dose, i.v.: 2 x 4, 8 and 12 mg/kg). The
      conjugates showed significantly reduced toxicity (reduced lethality and body
      weight loss) with a concomitantly stable or slightly improved antitumour activity
      compared to free doxorubicin. At the dose of 12 mg/kg mortality was unacceptably
      high in the doxorubicin treated group ( approximately 80%); in contrast, no
      mortality was observed with the conjugate treated animals with body weight loss <
      10 %. In a further experiment, therapy with the acid-sensitive doxorubicin
      albumin conjugate at 3 x 12 mg/kg in the MDA-MB-435 model resulted in a
      significantly improved antitumour activity over free doxorubicin at its optimal
      dose of 2 x 8 mg/kg. In conclusion, acid-sensitive transferrin and albumin
      doxorubicin conjugates can be administered at higher doses than free doxorubicin
      in nude mice models with a concomitant improvement in antitumour activity.
      Interestingly, there is no pronounced difference between identically constructed
      transferrin and albumin doxorubicin conjugates with regard to in vitro or in vivo
      efficacy.

PMID- 11328659
TI  - Site-specific administration of antisense oligonucleotides using biodegradable
      polymer microspheres provides sustained delivery and improved subcellular
      biodistribution in the neostriatum of the rat brain.
AB  - Antisense oligonucleotides (ODNs) are being increasingly used in the central
      nervous system as biological tools, as drug-target validation agents and as
      potential therapeutic agents. Although the local delivery of naked ODNs to the
      brain can result in the desired biological effects, the duration of efficacy is
      relatively short lived due to the combined effects of rapid ODN degradation and
      elimination half-lives in vivo. In this study, we have examined the use of
      biodegradable polymer microspheres as a site-specific delivery system for
      targeting ODNs to the neostriatum of the rat brain. Model phosphorothioate
      backbone-modified ODNs were entrapped within poly(D,L-lactide-co-glycolide)
      (PLAGA) microspheres using a double emulsion-deposition method and the
      formulations characterised in terms of particle size, surface morphology, percent
      encapsulation efficiency, ODN loading and in vitro release profiles. For in vivo
      evaluation, PLAGA microspheres containing fluorescently-labelled ODNs were stereo
      taxically administered to the neostriatum of the rat brain and biodistribution of
      ODNs monitored after 48 h. Administration of free fluorescently-labelled ODNs to
      the neostriatum resulted in a punctate cellular distribution of ODNs after 24 h
      with little or no ODN remaining in the neostriatum after 48 h. In comparison,
      fluorescently-labelled ODNs delivered using polymer microspheres were intensely
      visible in cells after 48 h post-administration and the fluorescence appeared to
      be diffuse covering both cytosolic and nuclear regions. Dual-label
      immunohistochemical analyses suggested that ODNs were mainly distributed to
      neuronal cells. These data indicate that site-specific administration of ODNs
      using biodegradable polymer microspheres will not only provide sustained delivery
      of nucleic acids but can also improve the cellular distribution of ODNs to brain
      cells. Sustained or controlled-release biodegradable polymer formulations,
      therefore, represent an attractive strategy for improved local delivery of ODNs
      to the CNS.

PMID- 11328660
TI  - Interactions of PC/Chol and PS/Chol liposomes with human cells in vitro.
AB  - Interactions between phosphatidylcholine (PC) or phosphatidylserine (PS)
      liposomes and human umbilical vein endothelial cells (HUVEC) or human
      promyelocytic leukemia cells (HL60) were investigated. Pyramine encapsulating or
      rhodamine incorporating small unilamellar liposomes with mean diameters around 80
      nm (demonstrated to retain encapsulated material and to be nontoxic under
      experimental conditions) were used. Liposome uptake by both types of cells
      increased when increasing amounts of vesicles were co-incubated. For both lipid
      compositions, the interaction with HUVEC was very fast (association reached a
      plateau within 5 min) and so was the release of internalized vesicles (90% within
      10 min at 37 degrees C). The reduced association values at 4 degrees C and the
      punctuate fluorescence observed in the cell cytoplasm after interaction, were
      indicative of whole liposome internalization. This internalization was clathrin
      independent, since it was not inhibited by sodium azide and deoxyglucose. Pre
      treatment of HUVEC with filipin or NEM resulted in modification of the
      interaction, something that could be due to alterations in the biochemical
      characteristics of HUVEC membranes that inhibit vesicular processes. In HL-60
      cells, a slower association and faster release of PC/Chol liposomes was
      demonstrated, while association of both liposomes with these cells was energy-and
      temperature-independent. Nevertheless, morphological studies revealed differences
      in the interactions: A bright fluorescent rim observed after interaction with
      PC/Chol liposomes, suggests that these liposomes were adsorbed on the surface of
      HL60 cells, while the uniform cytoplasmic fluorescence observed after incubation
      with PS/Chol liposomes was indicative of fusion as the interaction mechanism.

PMID- 11328661
TI  - Targeted drug delivery to the brain; (blood-brain barrier, efflux, endothelium,
      biological transport).

PMID- 11328662
TI  - mRna expression and transport characterization of conditionally immortalized rat
      brain capillary endothelial cell lines; a new in vitro BBB model for drug
      targeting.
AB  - Brain capillary endothelial cell lines (TR-BBB) were established from a recently
      developed transgenic rat harboring temperature-sensitive simian virus 40 (ts SV
      40) large T-antigen gene (Tg rat) and used to characterize the endothelial
      marker, transport activity, and mRNA expression of transporters and tight
      junction strand proteins at the blood-brain barrier (BBB). These cell lines
      expressed active large T-antigen and grew well at 33 degrees C with a doubling
      time of about 22-31 hr, but did not grow at 39 degrees C. TR-BBBs expressed the
      typical endothelial marker, von Willebrand factor, and exhibited acetylated low
      density lipoprotein uptake activity. Although the gamma-glutamyltranspeptidase
      activity in TR-BBBs was approximately 13% of that of the brain capillary fraction
      of a normal rat, it was localized in the apical side, suggesting that it reflects
      the functional polarity of the in vivo BBB. The mRNA of tight-junction strand
      proteins such as claudine-5, occludin, and junctional adhesion molecule are
      expressed in TR-BBB13. Drug efflux transporter, P-glycoprotein, with a molecular
      weight of 170 kDa was expressed in all TR-BBBs and mdr 1a, mdr 1b, and mdr 2 mRNA
      were detected in TR-BBBs using RT-PCR. Moreover, mrp1 mRNA was expressed in all
      TR-BBBs. Influx transporter, GLUT-1, expressed at 55 kDa was revealed by Western
      blot analysis. It had 3-O-methyl-D-glucose (3-OMG) uptake activity which was
      concentration-dependent with a Michaelis-Menten constant of 9.86 +/- 1.20 mM. The
      mRNA of large neutral amino acid transporter, which consists of LAT-1 and 4F2hc
      was expressed in TR-BBBs. In conclusion, the conditionally immortalized rat brain
      capillary endothelial cell lines (TR-BBB) had endothelial makers, expressed mRNA
      for tight-junction strand proteins and the influx and efflux transporters and
      produced GLUT-1, which is capable of 3-OMG transport activity.

PMID- 11328663
TI  - Improved brain delivery of a nonsteroidal anti-inflammatory drug with a synthetic
      glyceride ester: a preliminary attempt at a CNS drug delivery system for the
      therapy of Alzheimer's disease.
AB  - 1,3-Diacetyl-2-ketoprofen glyceride (DAKG), a prodrug of ketoprofen, was
      synthesized as a model compound in our attempt to develop a central nervous
      system (CNS) drug delivery system to treat Alzheimer's disease. The primary
      purpose of the present study is to test whether DAKG improves the delivery of
      ketoprofen to the brain and to quantitatively evaluate several factors that
      influence the brain distribution of this prodrug. ddY mice were injected with
      either ketoprofen or DAKG at a dose of 40 micromol/kg and then the plasma and
      brain pharmacokinetics of these agents were assessed. The brain uptake clearance
      of ketoprofen and DAKG across the BBB was measured by in situ mouse brain
      perfusion. In addition, the efflux permeability of ketoprofen through the BBB was
      evaluated using the in vivo mouse brain microdialysis technique. The in vivo
      metabolism of DAKG in the brain was assessed by a short infusion into the
      internal carotid artery coupled with the brain metabolism index (BMI) method.
      Administration of DAKG produced an approximately 3-fold increase in the area
      under the brain concentration - time curve of ketoprofen, compared with
      administration of ketoprofen itself. The brain uptake clearance (CL(in) ) of
      ketoprofen across the BBB was 0.0308 +/- 0.0046 mL/min/g whereas the CL(in) of
      DAKG was 1.60 +/- 0.16 mL/min/g, suggesting a marked increase in BBB permeability
      following lipidization of ketoprofen. The BMI method confirmed that DAKG is taken
      up by the brain to rapidly release ketoprofen in a dose-dependent manner. The in
      vitro metabolism studies revealed that isolated bovine brain capillaries as well
      as whole brain homogenate have the hydrolysis activity to DAKG. In addition, the
      brain concentration of ketoprofen after DAKG administration was maintained for a
      significant period following co-administration of probenecid. These results
      suggest that DAKG improves the delivery of ketoprofen to the brain, and this
      improved delivery is due to avid uptake of DAKG across the BBB followed by rapid
      hydrolysis to ketoprofen within the brain. The ketoprofen produced in the brain
      was probably cleared by the active efflux system operating in the BBB.
      Significant inhibition of this efflux system by co-administration of probenecid
      could result in a sustained concentration of ketoprofen in the brain following
      DAKG administration.

PMID- 11328664
TI  - Blood-brain barrier transport of H1-antagonist ebastine and its metabolite
      carebastine.
AB  - The transport mechanism of the non-sedative H1-antagonist ebastine and its first
      pass carboxylic acid metabolite carebastine at the blood-brain barrier (BBB) was
      studied. In rats, the brain uptake index (BUI) value of [14 C]carebastine was
      significantly lower than that of [14 C]ebastine. The BUI value of [14
      C]carebastine was greatly increased by the addition of non-labeled carebastine.
      The steady-state uptake of [14 C]carebastine by P-glycoprotein-overexpressing
      K562/ADM cells was significantly lower than that by their parental drug-sensitive
      cell line K562. The decreased steady-state uptake of [14 C]carebastine by
      K562/ADM cells was reversed by verapamil. Steady-state uptake of [14
      C]carebastine by primary cultured bovine brain capillary endothelial cells
      (bovine BCECs) was increased in the presence of metabolic inhibitors and
      verapamil. Non-labeled carebastine increased the steady-state uptake of a P
      glycoprotein substrate, [3 H]vincristine, by bovine BCECs. The initial uptake of
      [3 H]mepyramine by bovine BCECs and RBEC1 (an immortalized cell line from rat
      brain capillary endothelial cells) was strongly inhibited by ebastine, while
      zwitterionic carebastine was slightly inhibitory. The values of brain-to-plasma
      unbound concentration ratio (Kp,f) in mdr1a(-/-) mice were increased 5.3-fold and
      4.2-fold for [14 C ebastine and for [14 C]carebastine, respectively, compared
      with those in mdr1a(+/+) mice. Non-radiolabeled carebastine increased the Kp,f
      values of [14 C]carebastine in both types of mice. In conclusion, carebastine was
      shown to be a substrate for P-glycoprotein-mediated efflux from the brain at the
      BBB. A second efflux system may also be involved. The relatively low affinity of
      the uptake transport system for carebastine also limits the brain distribution of
      ebastine/carebastine.

PMID- 11328665
TI  - Blood-brain barrier transport of L-tyrosine Conjugates: a model study for the
      brain targeting using large neutral amino acid transport system.
AB  - We examined the relation ship between the charge of the amino or carboxylic
      function of a substrate and the substrate recognition by the large neutral amino
      acid (LNAA) transport carrier, using the in situ brain perfusion technique.
      Glucose-coupled L-tyrosine (GcpY), which has a free carboxylic function, and 2-(L
      tyrosylamide)-2-deoxy-D-glucose (Y-2DG), which has a free amino function were
      synthesized. The inhibitory effect of GcpY on [3 H]L-tyrosine uptake was larger
      than that of N-methly-L-phenylalanine or N-acetyl-L-phenylalanine, whereas Y-2DG
      did not affect it. These results indicate that a free amino group is not required
      for recognition, provided that the modified amino group is able to take a
      positive charge. Steric factors appeared to be relatively unimportant.

PMID- 11328666
TI  - Cloning and expression in Pichia pastoris of a genetically engineered single
      chain antibody against the rat transferrin receptor.
AB  - The present investigation describes the construction of a genetically engineered
      single chain antibody (scFv) against the rat transferrin receptor (OX26), and
      demonstrates that this scFv antibody can be fully processed and expressed as a
      soluble secreted molecule in the methylotrophic yeast Pichia pastoris.
      Restriction endonuclease sites located at both 5'- and 3'-flanking regions of
      OX26 coding region in the prokaryote pOPE-OX26 vector were engineered to
      incorporate yeast compatible restriction endonuclease sites (i.e. EcoRI and SmaI
      or AvrII). The modified OX26 cDNA was subcloned into the Pichia expression
      vectors pPIC9 and pHIL-S1. An OX26 scFv high producer clone [GS115 His+ Mut+
      (pPIC-OX26 SacI)] was isolated and used for large-scale production and
      characterization. Because the engineered scFv contains both a c-myc tag and a
      (His)5 tail, the OX26 scFv was purified to homogeneity by immobilized metal
      affinity chromatography. The identity of the OX26 scFv was confirmed by Western
      blot analyses with both anti c-myc and anti poly-His antibodies. Minor
      immunoreactive bands corresponding to hyperglycosylated and partially processed
      alpha-factor leader prosequence were also detected in the purified OX26 scFv, and
      these contaminants were markedly reduced when the expression of the OX26 scFv was
      performed in minimal methanol medium buffered with phosphate at pH = 7. The
      present investigation suggests that this expression system may be useful for the
      production of anti-receptor single chain antibodies that can be used as brain
      drug delivery vectors.

PMID- 11328667
TI  - Drug targeting to the brain using avidin-biotin technology in the mouse; (blood
      brain barrier, monoclonal antibody, transferrin receptor, Alzheimer's disease).
AB  - A beta1-40 peptide radiopharmaceuticals could be used to image A beta brain
      amyloid in transgenic mouse models of Alzheimer's disease should the A beta
      peptide radiopharmaceutical be made transportable through the blood-brain barrier
      (BBB) in vivo. The present studies used the RI7-217 rat monoclonal antibody to
      the mouse transferrin receptor as a BBB drug targeting vector for the delivery to
      brain of A beta1-40 radiolabeled with either 125-Iodine or 111-Indium. The A beta
      peptide radiopharmaceutical is conjugated to the RI7 MAb using avidin biotin
      technology, wherein the A beta1-40 peptide radiopharmaceutical is
      monobiotinylated (bio) and bound to a conjugate of the RI7 MAb and streptavidin
      (SA). The [125 I]-bio-A beta1-40 or the [111 In]-bio-A beta1-40 either free or
      bound to the RI7/SA conjugate was injected intravenously into anesthetized adult
      mice and plasma pharmacokinetics and organ uptake were measured over the next 60
      minutes. The A beta1-40 peptide radiopharmaceutical radiolabeled with 111-Indium
      was the preferred formulation, compared to peptide labeled with 125-Iodine,
      because there was a greater metabolic stability and reduced artifactual organ
      uptake of metabolites associated with the use of the 111-Indium nuclide. However,
      biotinylated A beta1-40 peptide radiopharmaceuticals conjugated to the RI7/SA
      brain drug targeting system were metabolically unstable in mice in vivo owing to
      active biotinidase activity. Future work involving brain drug targeting in mice
      that utilizes avidin biotin technology will need to incorporate biotin analogues
      that are resistant to biotinidase.

PMID- 11328668
TI  - Stability of the disulfide bond in an avidin-biotin linked chimeric peptide
      during in vivo transcytosis through brain endothelial cells.
AB  - Drug delivery of potential neuropharmaceuticals with poor intrinsic permeability
      through the blood-brain barrier (BBB), such as peptides, is facilitated by
      coupling to a vector that undergoes receptor-mediated transcytosis through the
      endothelial cells of brain microvessels. When cleavable disulfide linkers are
      used in the synthesis of such "chimeric peptides", it is crucial that the S-S
      bridge is stable during transcytosis. Cleavage within endothelial cells could
      result in sequestration of the drug moiety instead of passage through the BBB. In
      the present study the metabolically stable opioid peptide [3 H]DALDA ([3 H]Tyr
      DArg-Phe-Lys-NH2 ) was used as a model drug. It was monobiotinylated with the
      cleavable biotin reagent sulfosuccinimidyl 2-(biotinamido)ethyl-1,3'
      dithiopropionate (NHS-SS-biotin) to obtain bio-[3 H]DALDA. The biotinylated
      peptide was then bound to a vector for brain delivery after intravenous injection
      in rats, a covalent conjugate of streptavidin and the transferrin receptor
      monoclonal antibody, OX26. Compared to peptide without vector, brain uptake of
      bio-[3 H]DALDA after was increased 18-fold to reach 0.12% of the injected dose
      per g tissue. Transcranial microdialysis was performed for 60 min after an
      intravenous bolus of chimeric peptide, followed by reverse phase HPLC of
      dialysate. Stability of the chimeric peptide during transport through the BBB
      into brain extracellular fluid was concluded from the absence of a peptide peak
      generated by disulfide cleavage.

PMID- 11328669
TI  - Endocytosis and transcytosis of an immunoliposome-based brain drug delivery
      system.
AB  - Immunoliposomes conjugated with the OX26 monoclonal antibody to the rat
      transferrin receptor can be used for brain delivery of small molecules. In the
      present study the uptake of OX26-immunoliposomes by target cells as well as their
      transcytosis across the blood-brain barrier was investigated. Microscopy of RG2
      rat glioma cells incubated with fluorescence labeled OX26-immunoliposomes
      revealed intracellular co-localization of liposomal cargo, the liposomal membrane
      bilayer and the OX26 monoclonal antibody. The distinct particulate staining
      pattern was indicative for accumulation of OX26-immunoliposomes within endosomal
      or lysosomal compartments. Prolonged incubations demonstrated endosomal release
      of the liposomal cargo propidium iodide to the cytoplasm. A maximum of 50% of
      propidium iodide was released from the endosomal compartment after 24 hours of
      incubation. Transcytosis was studied using an in vitro model of the blood-brain
      barrier consisting of immortalized RBE4 rat brain endothelial cells. OX26
      immunoliposomes did permeate across the RBE4 cell monolayer and showed a
      permeability coefficient of P(app) = 1.6 x 10(-5) ml/s. Transport was inhibited
      at low temperature, by competition with free OX26 or by exchanging the OX26
      monoclonal antibody for an unspecific isotype antibody. Transcytosis of OX26
      immunolipsomes was confirmed in vivo by the brain perfusion and capillary
      depletion technique. OX26-immunoliposomes were detected within the post-vascular
      compartment of brain parenchyma (PS product = 2.4 microl/g/min.) and were not
      associated with the brain microvasculature.

PMID- 11328670
TI  - Invited review: manganese superoxide dismutase in disease.
AB  - Manganese superoxide dismutase (MnSOD) is essential for life as dramatically
      illustrated by the neonatal lethality of mice that are deficient in MnSOD. In
      addition, mice expressing only 50% of the normal compliment of MnSOD demonstrate
      increased susceptibility to oxidative stress and severe mitochondrial dysfunction
      resulting from elevation of reactive oxygen species. Thus, it is important to
      know the status of both MnSOD protein levels and activity in order to assess its
      role as an important regulator of cell biology. Numerous studies have shown that
      MnSOD can be induced to protect against pro-oxidant insults resulting from
      cytokine treatment, ultraviolet light, irradiation, certain tumors, amyotrophic
      lateral sclerosis, and ischemia/reperfusion. In addition, overexpression of MnSOD
      has been shown to protect against pro-apoptotic stimuli as well as ischemic
      damage. Conversely, several studies have reported declines in MnSOD activity
      during diseases including cancer, aging, progeria, asthma, and transplant
      rejection. The precise biochemical/molecular mechanisms involved with this loss
      in activity are not well understood. Certainly, MnSOD gene expression or other
      defects could play a role in such inactivation. However, based on recent findings
      regarding the susceptibility of MnSOD to oxidative inactivation, it is equally
      likely that post-translational modification of MnSOD may account for the loss of
      activity. Our laboratory has recently demonstrated that MnSOD is tyrosine
      nitrated and inactivated during human kidney allograft rejection and human
      pancreatic ductal adenocarcinoma. We have determined that peroxynitrite (ONOO- )
      is the only known biological oxidant competent to inactivate enzymatic activity,
      to nitrate critical tyrosine residues, and to induce dityrosine formation in
      MnSOD. Tyrosine nitration and inactivation of MnSOD would lead to increased
      levels of superoxide and concomitant increases in ONOO- within the mitochondria
      which, could lead to tyrosine nitration/oxidation of key mitochondrial proteins
      and ultimately mitochondrial dysfunction and cell death. This article assesses
      the important role of MnSOD activity in various pathological states in light of
      this potentially lethal positive feedback cycle involving oxidative inactivation.

PMID- 11328671
TI  - Effect of obesity and troglitazone on expression of two glutathione peroxidases:
      cellular and extracellular types in serum, kidney and adipose tissue.
AB  - To determine the effect of obesity on expression of cellular- (C-) and
      extracellular (EC-) glutathione peroxidase (GPX) in serum, kidney and adipose
      tissue, we measured GPX in serum, kidneys and adipose tissue of the obese Otsuka
      Long-Evans-Tokushima Fatty (OLETF) rat and its lean counterpart (LETO). We also
      investigated the effect of troglitazone. Five each of OLETF and LETO rats were
      fed diet with or without 0.2% troglitazone for 10 days. Final body weight, kidney
      weight, blood glucose and serum tumor necrosis factor-alpha (TNF-alpha) level
      were higher in OLETF rats than in LETO rats. Serum and kidney GPX activities were
      higher, but adipose tissue GPX activity was lower, in OLETF rats than in LETO
      rats. Troglitazone treatment decreased adipose tissue GPX activity and abolished
      overproduction of TNF-alpha in OLETF rats. Immunoblot analysis, for the first
      time, revealed that both obesity and troglitazone suppressed the protein signals
      for C-GPX and EC-GPX in adipose tissue. Serum protein carbonyl groups were
      increased in OLETF rats and troglitazone completely blocked this increase.
      Increased serum GPX activity in obese rat was due to the increased secretion of
      EC-GPX from the kidney. Troglitazone protected against the enhanced oxidative
      stress induced by obesity independently of the serum GPX concentration.

PMID- 11328672
TI  - The dose-dependent effect of copper-chelating agents on the kinetics of
      peroxidation of low-density lipoprotein (LDL).
AB  - Copper-induced peroxidation of lipoproteins involves continuous production of
      free radicals via a redox cycle of copper. Formation of Cu(I) during Cu(II)
      induced peroxidation of LDL was previously demonstrated by accumulation of the
      colored complexes of Cu(I) in the presence of one of the Cu(I)-specific chelators
      bathocuproine (BC) or neocuproine (NC). All the studies conducted thus far
      employed high concentrations of these chelators (chelator/Cu(II) > 10). Under
      these conditions, at low copper concentrations the chelators prolonged the lag
      preceding oxidation, whereas at high copper concentrations the chelators
      shortened the lag. In an attempt to gain understanding of these non-monotonic
      effects, we have studied systematically the peroxidation of LDL (0.1 microM, 50
      microg protein/mL) at varying concentrations of NC or BC over a wide range of
      concentrations of the chelators and copper. These studies revealed that: (i) At
      copper concentrations of 5 microM and below, NC prolonged the lag in a monotonic,
      dose-dependent fashion typical for other complexing agents. However, unlike with
      other chelators, the maximal rate of oxidation was only slightly reduced (if at
      all). (ii) At copper concentrations of 15 microM and above, the addition of about
      20 microM NC or BC resulted in prolongation of the lag, but this effect became
      smaller at higher concentrations of the chelators, and at yet higher
      concentrations the lag became much shorter than that observed in the absence of
      chelators. Throughout the whole range of NC concentrations, the maximal rate of
      peroxidation increased monotonically upon increasing the NC concentration. (iii)
      Unlike in the absence of chelators, the prooxidative effect of copper did not
      exhibit saturation with respect to copper, up to copper concentrations of 30
      microM. Based on these results we conclude that the copper-chelates can partition
      into the hydrophobic core of LDL particles and induce peroxidation by forming
      free radicals within the core. This may be significant with respect to the
      understanding of the possible mechanisms of peroxidation by chelated transition
      metals in vivo.

PMID- 11328673
TI  - Trypanosoma cruzi trypanothione reductase is inactivated by peroxidase-generated
      phenothiazine cationic radicals.
AB  - Trypanosoma cruzi trypanothione reductase (TR) was irreversibly inhibited by
      peroxidase/H2O2 /phenothiazine (PTZ) systems. TR inactivation depended on (a)
      time of incubation with the phenothiazine system; (b) the peroxidase nature and
      (c) the PTZ structure and concentration. With the most effective systems, TR
      inactivation kinetics were biphasic, with a relatively fast initial phase during
      which about 75% of the enzyme activity was lost, followed by a slower phase
      leading to total enzyme inactivation. GSH prevented TR inactivation by the
      peroxidase/H2O2/PTZ+* systems. Production of PTZ+* cation radicals by PTZ
      peroxidation was essential for TR inactivation. Horseradish peroxidase, leukocyte
      myeloperoxidase (MPO) and the pseudo-peroxidase myoglobin (Mb) were effective
      catalysts of PTZ+* production. Promazine, thioridazine, chlorpromazine,
      propionylpromazine prochlorperazine, perphenazine and trimeprazine were effective
      constituents of the HRP/H2O2 /PTZ system. The presence of substituents at the PTZ
      nucleus position 2 exerted significant influence on PTZ activity, as shown by the
      different effects of 2-trifluoromethyl and 2-H or 2-chlorophenothiazines. The
      PTZ+* cation radicals disproportionation regenerated the non-radical PTZ molecule
      and produced the PTZ sulfoxide that was inactive on TR. Thiol compounds including
      GSH interacted with PTZ+* cation radicals transferring an electron from the
      sulfide anion to the PTZ+*, thus nullifying the PTZ+* biological and chemical
      activities.

PMID- 11328674
TI  - Reduction of carbon tetrachloride-induced rat liver injury by IRFI 042, a novel
      dual vitamin E-like antioxidant.
AB  - Carbon tetrachloride (CCl4 )-induced hepatotoxicity is likely the result of a
      CCl4 -induced free radical production which causes membrane lipid peroxidation
      and activation of transcription factors regulating both the TNF-alpha gene and
      the early-immediate genes involved in tissue regeneration. IRFI 042 is a novel
      vitamin E-like compound having a masked sulphydryl group in the aliphatic side
      chain. We studied the effect of IRFI 042 on CCl4 -induced liver injury. Liver
      damage was induced in male rats by an intraperitoneal injection of CCl4 (1 ml/kg
      in vegetal oil). Serum alanine aminotransferase (ALT) activity, liver
      malondialdehyde (MAL), hydroxyl radical formation (OH*), calculated indirectly by
      a trapping agent, hepatic reduced glutathione (GSH) concentration, plasma TNF
      alpha, liver histology and hepatic mRNA levels for TNF-alpha were evaluated 48 h
      after CCl4 administration. Hepatic vitamin E (VE) levels were evaluated, in a
      separate group of animals, 2 h after CCl4 injection. A control group with vitamin
      E (100 mg/kg) was also treated in order to evaluate the differences versus the
      analogue treated groups. Intraperitoneal injection of carbon tetrachloride
      produced a marked increase in serum ALT activity (CCl4 = 404.61 +/- 10.33 U/L;
      Controls= 28.54 +/- 4.25 U/L), liver MAL (CCl4 = 0.67 +/- 0.16 nmol/mg protein;
      Controls= 0.13 +/- 0.06 nmol/mg protein), OH(7) levels assayed as 2,3-DHBA (CCl4
      = 8.73 +/- 1.46 microM; Controls= 0.45 +/- 0.15 microM) and 2,5-DHBA (CCl4 =
      24.61 +/- 3.32 microM; Controls= 2.75 +/- 0.93 microM), induced a severe
      depletion of GSH (CCl4 = 3.26 +/- 1.85 micromol/g protein; Controls= 17.82 +/-
      3.13 micromol/g protein) and a marked decrease in VE levels (CCl4 = 5.67 +/- 1.22
      nmol/g tissue; Controls= 13.47 +/- 3.21 nmol/g tissue), caused liver necrosis,
      increased plasma TNF-alpha levels (CCl4 = 57.36 +/- 13.24 IU/ml; Controls= 7.26
      +/- 2.31 IU/ml) and enhanced hepatic mRNA for TNF-alpha (CCl4 = 19.22 +/- 4.38
      a.u.; Controls= 0.76 +/- 0.36 a.u.). IRFI 042 (100 mg/kg, 30 min after CCl4
      injection) blunted liver MAL (0.32 +/- 0.17 nmol/mg protein), decreased the serum
      levels of ALT (128.71 +/- 13.23 U/L), and restored the hepatic concentrations of
      VE (9.52 +/- 3.21 nmol/g tissue), inhibited OH* production (2,3-DHBA= 3.54 +/-
      1.31 microM; 2,5-DHBA= 7.37 +/- 2.46 microM), restored the endogenous antioxidant
      GSH (12.77 +/- 3.73 mmol/g protein) and improved histology. Furthermore IRFI 042
      treatment suppressed plasma TNF-alpha concentrations (31.47 +/- 18.25 IU/ml) and
      hepatic TNF-alpha mRNA levels (11.65 +/- 3.21 a.u.). The acute treatment with
      vitamin E failed to exert any protective effect against CCl4 -induced
      hepatotoxicity. These investigations suggest that IRFI 042 treatment may be of
      benefit during free radical-mediated liver injury.

PMID- 11328675
TI  - Retinol supplementation induces oxidative stress and modulates antioxidant enzyme
      activities in rat sertoli cells.
AB  - Recent intervention studies revealed that supplementation with retinoids resulted
      in a higher incidence of lung cancer. Recently the causal mechanism has begun to
      be clarified. We report here that retinol caused cellular oxidative stress and
      modulated superoxide dismutase, catalase and glutathione peroxidase activities.
      Retinol (7 microM) significantly increased TBARS, conjugated dienes, and
      hydroperoxide-initiated chemiluminescence in cultured Sertoli cells. In response
      to retinol treatment superoxide dismutase, catalase and glutathione peroxidase
      activities increased. TBARS content and catalase activities were decreased by a
      free radical scavenger. These findings suggest that retinol may induce oxidative
      stress and modulate antioxidant enzyme activities in Sertoli cells.

PMID- 11328676
TI  - Cyanide-resistant alternative respiration is strictly correlated to intracellular
      peroxide levels in Acremonium chrysogenum.
AB  - A strict correlation between the intensity of the cyanide-resistant alternative
      respiratory pathway and the intracellular peroxide levels in the cephalosporin C
      producer filamentous fungus Acremonium chrysogenum was demonstrated.
      Intracellular peroxide levels increased in a dose-dependent manner after addition
      of H2O2 to the culture media. A similar phenomenon was observed due to the
      specific inhibition of catalase by salicylic acid. In both cases, cyanide
      resistant respiration was markedly stimulated. On the other hand, both cyanide
      resistant respiration and intracellular peroxide levels were effectively
      suppressed by the lipid peroxyl radical scavenger DL-alpha-tocopherol, which
      breaks lipid peroxidation chains effectively. Our findings firmly supported the
      assumption that there is a connection between the intracellular peroxide levels
      and the intensity of the alternative respiratory pathway in fungi.

PMID- 11328677
TI  - Comparison of the radical trapping ability of PBN, S-PPBN and NXY-059.
AB  - The nitrones alpha-phenyl-N-tert-butyl nitrone (PBN), sodium 2-sulfophenyl-N-tert
      butyl nitrone (S-PBN) and disodium 2,4-disulfophenyl-N-tert-butyl nitrone (NXY
      059) are neuroprotective in a variety of rodent models. The objective of the
      current studies was to compare the ability of PBN, S-PBN, and NXY-059 to form
      radical adducts and to prevent salicylate oxidation in an aqueous system. For the
      electron spin resonance (ESR) studies, hydroxyl radicals were generated with
      ultraviolet (UV) light and hydrogen peroxide. Secondary radicals were then
      produced by the addition of methanol, ethanol, isopropanol, dimethylsulfoxide,
      tetrahydrofuran or 1,4-dioxane. In addition, competition spin trapping studies
      were performed using PBN-alpha-(13) C and either S-PBN or NXY-059. In the
      salicylate studies, PBN, S-PBN and NXY-059 were compared to a variety of other
      antioxidants and reference compounds (cysteine, glutathione, ascorbate, uric
      acid, Tempo, Trolox, and Tirilizad) for their ability to prevent 2,3- and 2,5
      dihydroxybenzoic acid formation induced by hydroxyl radical generating systems.
      All 3 nitrones trapped carbon- and oxygen-centered radicals to produce ESR
      detectable radical adducts. Each nitrone also prevented salicylate oxidation,
      with PBN being the most effective. The ability of these 3 nitrones to prevent
      salicylate oxidation resembled that of most of the other compounds tested.

PMID- 11328678
TI  - Docosahexaenoic acid supplementation-increased oxidative damage in bone marrow
      DNA in aged rats and its relation to antioxidant vitamins.
AB  - We compared the influence of docosahexaenoic acid (DHA) supplementation on
      oxidative DNA damage in bone marrow between young and aged rats. As a marker of
      oxidative DNA damage, 8-hydroxydeoxyguanosine (8-OHdG) in DNA was analyzed. Young
      (5-week-old) and aged (100-week-old) female Wistar rats were given DHA (300mg/kg
      body weight/day) or vehicle (control) orally for 12 weeks. The 8-OHdG in the bone
      marrow in the aged DHA group was significantly higher than that in the other
      groups. Vitamin E concentrations, however, did not differ among the groups
      regardless of the DHA supplementation. Vitamin C (ascorbic acid) concentrations
      in the aged control group were approximately 1/2 those in the young control
      group. The concentrations of vitamin C tended to be higher in the young DHA group
      and lower in the aged DHA group when compared to their respective control groups.
      Changes in the concentrations of vitamin C and vitamin E in plasma were similar
      to those in the bone marrow. The activity of hepatic l-gulono- gamma -lactone
      oxidase, an enzyme responsible for vitamin C synthesis, corresponded well to the
      concentrations of vitamin C in the bone marrow and the plasma. These results
      suggest that in aged rats, but not young rats, excess supplementation of DHA
      induces oxidative DNA damage in bone marrow and that the decrease in vitamin C
      synthesis in aged rats is involved in the mechanisms of DNA damage.

PMID- 11328679
TI  - Relationship of brain MRI abnormalities and physical functional status in chronic
      fatigue syndrome.
AB  - Chronic Fatigue Syndrome (CFS) is an unexplained illness that is characterized by
      severe fatigue. Some have suggested that CFS is a "functional somatic syndrome"
      in which symptoms of fatigue are inappropriately attributed to a serious illness.
      However, brain magnetic resonance imaging (MRI) data suggest that there may be an
      organic abnormality associated with CFS. To understand further the significance
      of brain MRI abnormalities, we examined the relationship between MRI identified
      brain abnormalities and self-reported physical functional status in 48 subjects
      with CFS who underwent brain MR imaging and completed the Medical Outcomes Study
      SF-36. Brain MR images were examined for the presence of abnormalities based on 5
      general categories previously shown to be sensitive to differentiating CFS
      patients from healthy controls. There were significant negative relationships
      between the presence of brain abnormalities and both the physical functioning
      (PF) (rho=-.31, p=.03), and physical component summary PCS (rho=-.32, p=.03)
      subscales of the SF-36. CFS patients with MRI identified brain abnormalities
      scored significantly lower on both PF (t(1,46) =2.3, p=.026) and the PCS (t(1,41)
      =2.4, p=.02) than CFS subjects without an identified brain abnormality. When
      adjusted for age differences only the PF analysis remained significant. However,
      the effect sizes for both analyses were large indicating meaningful differences
      in perceived functional status between the groups. These results demonstrate that
      the presence of brain abnormalities in CFS are significantly related to
      subjective reports of physical function and that CFS subjects with MRI brain
      abnormalities report being more physically impaired than those patients without
      brain abnormalities.

PMID- 11328680
TI  - Digital vision theory: Boolean logic model.
AB  - Guild (1932) stated the general requirements for processing signals in color
      vision system and a digital format of his paradigm is developed in this paper.
      The disk structure generates the digital receptor pulse. The input modalities
      form sets, linked by intersections, joins, and complement junctions. The synapses
      are elements in these junctions. Complex synapses form junctions to create
      Boolean logic processing. A computer program using these Boolean logic functions
      calculates: Light and dark adaptation responses; Color matching and spectral
      coordinate functions; Chromatic adaptation; Color shift responses; and Dynamic
      neural responses. These calculations compare favorably with the experimental
      data. The processing criteria for signals in the vision system are given by Guild
      (1932). The analysis in this paper uses his criteria to develop a model of the
      vision system. A computer program simulates the digital processing of signals
      from the external photon source to the neural output signals from the ganglion
      cells in the inner-plexiform layer. The responses are compared with the responses
      of actual vision systems.

PMID- 11328681
TI  - Age related changes in inhibitory control as measured by stop signal task
      performance.
AB  - A modified version of the stop signal task (suitable for use with very young
      children) was administered to a pre primary school group of children (<5 years, 6
      months); a young primary group (5 years, 7 months to 7 years, 6 months); a mid
      primary group (7 years, 7 months to 9 years, 6 months) and a group of adults.
      Significant age differences in the ability to inhibit responding were found.
      These results highlight the need for measures of response inhibition which are
      appropriate for use with very young children, when the first signs of inhibitory
      skills are emerging. It is also imperative that such measures allow the
      assessment of skills across a broad range of age groups in order to
      comprehensively monitor their development.

PMID- 11328682
TI  - Normal spatial memory following postseizure treatment with ketamine: selective
      damage attenuates memory deficits in brain-damaged rodents.
AB  - Within 30 min after the initiation of status epilepticus (SE) by lithium and
      pilocarpine, rats were injected with either acepromazine or ketamine. Compared to
      the rats that had received the acepromazine, the group that had received the
      ketamine displayed more accurate spatial memory. Their scores did not differ
      significantly from normal (non-seized) controls. Although the ketamine treatment
      did not significantly change the amount of neuronal loss within about 100 Paxinos
      and Watson structures, it was neuroprotective for several structures within the
      thalamus and portions of the temporal and parietal cortices. Ketamine-treated
      rats, however, displayed markedly more damage within the entorhinal cortices and
      amygdalohippocampal area.

PMID- 11328683
TI  - Endogenous melatonin and epileptogenesis: facts and hypothesis.
AB  - In human epilepsy, diurnal variation in seizure phenomena suggests the
      involvement of a time-dependent biological signal. Clinical evidence indicates
      that in some cases, temporal clustering of epileptic seizures is in phase with
      the nocturnal rise in circulating melatonin. Although this hormone has been
      reported to stabilize the brain against seizure-producing stimuli, these
      pharmacological doses are not representative of physiological conditions but
      would nonetheless facilitate widespread inhibitory neurotransmission
      characteristic of traditional anticonvulsants. Instead, it is proposed that
      endogenous melatonin contributes to epileptiform activity through inhibitory
      actions on dopaminergic activity. Dopamine is considered a natural downregulator
      of seizure activity in a number of species, including humans, and numerous lines
      of evidence suggest that melatonin is capable of stimulating a decrease in
      dopamine output within areas of the brain thought to participate in the control
      of epileptic seizures. Pharmacological manipulation of the endogenous melatonin
      rhythm may provide a useful therapeutic strategy against the occurrence of
      seizures during increased hormone production.

PMID- 11328684
TI  - Sferics provoke changes in EEG power.
AB  - The present study investigated electrocortical and psychological influences of
      Very Low Frequency (VLF) sferics. Eighty female subjects, who were divided into
      two groups participated in the study. After a 10-minute baseline period the
      experimental group (n=40) underwent a 10-minute exposure to a previously recorded
      10 kHz-sferics impulse, which was presented with a pulse repetition frequency
      statistically varying between 1 and 3 Hz. After the sferics stimulation, an
      additional 20 minutes without treatment were recorded in order to examine
      possible prolonged sferics effects. The control group (n=40) received no
      treatment. As the physiological dependent measure, the background
      electroencephalogram (EEG) was registered throughout the course of the
      experiment. Absolute power values for different EEG frequency bands were
      determined by means of a Fast Fourier Transform (FFT) and compared between the
      two groups at four electrode sites (P3/P4; O1/O2). Also, the emotional and
      somatic state of the subjects and their ability consciously to perceive sferics
      were investigated. It could be shown that the two groups were characterized by
      different courses of EEG alpha and beta power. Whereas the sferics group
      displayed power increases in both frequency bands, which reached their maximum 20
      minutes after the end of exposure, the control group showed a slight power
      reduction. Sferics had no effect on the subjective state and could not be
      perceived consciously.

PMID- 11328685
TI  - GABA uptake by rabbit restiform body homogenates.
AB  - Restiform body (inferior cerebellar peduncle) preparations were obtained from
      rabbit brain stem slices and homogenized. When challenged with labelled GABA,
      these homogenates took it up briskly. We have characterized pharmacologically
      this uptake which resulted almost equally neuronal and glial. The neuronal
      component of the GABA uptake might be due to the adjacent cochlear nuclei coming
      along in the preparations, whereas the glial component probably belongs to the
      restiform body proper. Another possibility is that actually both components are
      due to the myelinated fibers and glia which make up the restiform body.

PMID- 11328686
TI  - Event-related potentials to threat-related faces in schizophrenia.
AB  - Specialised network disturbances such as abnormalities in processing faces, may
      be associated with functional disturbances of interpersonal communication in
      schizophrenia. This study focused on the temporal dimension, investigating facial
      processing deficits in patients with schizophrenia (and non-patient controls) in
      a passive event-related potential (ERP) paradigm. ERPs invoked to an angry and
      neutral face stimulus were recorded in 27 patients with schizophrenia and 27 age
      and sex matched normal controls. Patients with schizophrenia showed a significant
      generalised delay, and diminished P200 amplitude (primarily frontal) for both
      stimuli-with more widespread regions of disturbance associated with the angry
      face. Normal controls, on the other hand, showed relatively reduced posterior
      P200 amplitude for angry compared to neutral faces, and a lateralised pattern of
      engagement in response to both stimuli. These findings indicate suboptimal
      processing of neutral faces in patients with schizophrenia, further exacerbated
      for affect laden angry faces.

PMID- 11328687
TI  - Sex differences, gamma activity and schizophrenia.
AB  - This study explores the possibility that the more favourable clinical prognosis
      in females with schizophrenia may be associated with their greater network
      interconnectedness, which is possibly reflected in enhanced "Gamma" (40 Hz)
      electrical brain activity. An auditory "oddball" task was administered to 35
      patients with schizophrenia and 35 age and sex matched controls (25 males and 10
      females). Peak Gamma amplitude (from a time series of Gamma activity averaged for
      40 target stimuli, as well as the immediately preceding 40 background tones) was
      examined across 19 sites. Peak Gamma activity occurred 250 to 450 ms in targets
      and 350 to 550 ms in backgrounds. Multiple within and between group MANOVAs were
      undertaken analysing both Peak Gamma amplitude (microvolts) and latency
      (milliseconds). Within-group, the control males showed a pattern of earlier Gamma
      latency in the right compared with the left hemisphere (F(1, 33)=3.70, p<.06),
      while control females exhibited delayed latency frontally compared with the
      posterior region (F(1, 33)=6.25, p<.04). This male lateralization finding and the
      anterior/posterior gradient in females is consistent with Goldberg's model. The
      patient group however, failed to show this male lateralized and female frontal
      posterior pattern of Gamma activity, suggesting suboptimal network integration in
      the patient group, in both males and females.

PMID- 11328688
TI  - Binocular interaction and sensitivity to horizontal disparity in visual cortex in
      the awake monkey.
AB  - We evaluated the binocular interaction and horizontal disparity sensitivity in
      neurons recorded from macaque visual cortex. Neurons from V1 of three awake
      Macaca mulatta monkeys were isolated by means of extracellular recording and
      tested for disparity sensitivity with dynamic random dot stereograms. Neurons
      sensitive to horizontal disparities were stimulated both monocularly and
      binocularly with flashing bars and their responses quantified. ANOVA and
      regression tests were used for data analysis. Sixty-six cells out of 185 (66/185,
      36%) showed sensitivity to horizontal disparity. Disparity sensitive cells were
      grouped into near (25/66, 38%), tuned inhibitory (16/66, 24%), far (13/66, 20%)
      and tuned excitatory (12/66, 18%). Receptive fields of tuned cells were located
      more centrally in the visual field than those of near and far cells. The
      binocular interaction in tuned inhibitory cells increased linearly along with
      ocular unbalance. Most of tuned excitatory cells (10/12, 83%) showed facilitatory
      binocular interaction, characterized by a stronger response to binocular
      stimulation than to the stimulation of the dominant eye. On the contrary, most of
      tuned inhibitory cells (14/16, 88%) showed suppressory binocular interaction,
      characterized by a weaker response to binocular stimulation than to the
      stimulation of the dominant eye. Near and far cells showed both types of
      interaction in similar percentages. The binocular response showed a linear
      relationship with the sum of both monocular responses in tuned excitatory, tuned
      inhibitory and near cells, but not in far cells. Sensitivity to horizontal
      disparity may be a result of facilitatory and suppressive interactions between
      left and right inputs.

PMID- 11328689
TI  - Frequency domain equivalence between potentials and currents using LORETA.
AB  - Analyzing the preferences of brain regions to oscillate at specific frequencies
      gives important functional information. Application of discrete inverse solutions
      for the EEG/MEG inverse problem in the frequency domain usually involves the use
      of many current sources (sometimes 10(4) or more) restricted to gray matter
      points, as the solution space for the possible generators. This number can
      progressively increase with the level of detail of the MRI when it is used in co
      registration with EEG/MEG. However, the computation of the Fourier transform to
      all these sources is computationally intensive. We illustrate with a simple
      example how this procedure can be simplified by applying the Fourier transform to
      the signals in the sensors using a popular inverse method (LORETA). We also
      suggest how the search space of current sources at specific frequencies of
      oscillation can be limited to some regions constrained by other technologies such
      as fMRI, PET and SPECT.

PMID- 11328690
TI  - Mental organization according to the metabolism of information model and its
      mathematical description.
AB  - This paper outlines the concept of information metabolism, based on the
      structural organization of the biological cell. It was considered a model of
      states of consciousness (Kokoszka, 1993b) and human experiences (Kokoszka, 1999)
      reported earlier. The improved version of the graphical model is presented along
      with its preliminary description in the terms of dynamic systems. The possible
      application of the model to the design of artificial networks and into
      psychotherapeutic diagnosis discussed.

PMID- 11328691
TI  - Transient spinal inhibition induced by electrical stimulation of the rat brain.
AB  - Intracortical electrical stimulation of the rat brain using single pulse induced
      motor evoked potentials (MEPs) with shorter onset latencies in the bilateral
      extremity muscles. The MEPs appeared in the stimulation of cortical areas outside
      the motor cortex (MI) and subcortical areas. Train-pulse stimulation of the MI at
      a stimulus intensity just above the threshold induced MEPs with longer onset
      latency in muscles corresponding to the somatotopy of the MI stimulated. This
      implies that the potential characterizing shorter onset latency is equal to
      responses induced via the extrapyramidal tract, and responses with longer onset
      latency originate in the pyramidal tract. Corresponding to MEPs, we recorded two
      types of spinal potentials (SPs) via extrapyramidal and pyramidal tracts. In
      paired-pulse stimulation of the extrapyramidal tract, second MEPs showed a long
      lasting inhibition up to 3 s after the first MEPs, while the changes in second
      SPs were not remarkable. Extrapyramidal tract stimulation inhibited H-reflex in
      the same manner as MEPs. These results suggest that the electrical stimulation of
      rat brain has a long-lasting effect in inhibiting lower motoneuron
      excitabilities. Our method may be a useful experimental model to induce the
      transient inhibition of spinal motoneuron excitabilities caused by supraspinal
      structures.

PMID- 11328692
TI  - A layered neural continuum architecture in attention and seizure disorders.
AB  - Neural continuum theory concerns regions containing large numbers of neurons.
      Connections within a region are not specified and those between regions are
      probabilistic. Constituent cells can be treated as purely "excitatory" or
      "inhibitory." In a layered geometry, with a time delay between layers, delay is
      the variable controlling the linear behavior of the system, in particular, growth
      of small disturbances. Two layers of cells of opposite types structurally
      resemble and functionally model the attention centers of the brain (the reticular
      formation). Attention shifts among competing regions through changes in local
      inhibitory time waves and their spatial propagation. Increase in delay above a
      critical value, leads to large amplitude, spatially uniform activity; non-linear
      extension of the two-layer model predicts potentials in qualitative agreement
      with those observed during seizures. The preferentially amplified spatial
      frequency of normal waves remains relatively constant with delay. Since it is
      proportional to the locally varying mean lateral axonal extent, spatial-frequency
      is a signature by which the most compelling region can be recognized by higher
      brain centers.

PMID- 11328693
TI  - Relation between 1H MR spectroscopic imaging and regional cerebral glucose
      metabolism in Alzheimer's disease.
AB  - 1 H Magnetic resonance spectroscopic imaging (MRSI) and positron emission
      tomography (PET) of (18) F-2-fluoro-2-deoxy-D-glucose (FDG) were performed in 18
      patients with probable Alzheimer's disease (AD) and 3 normal controls. We
      measured the distribution and relative signal intensities of N-acetyl aspartate
      (NAA; a presumed neuronal marker), choline residues (Cho) representing cellular
      membrane compounds and of creatine-containing metabolites (Cr), and correlated
      these to regional cerebral glucose metabolism (rCMRGI) after coregistration of
      both imaging-techniques. The pattern of choline was significantly different
      between AD and normals (p < 0.01). RCMRGI was significantly related to Cho/Cr (r=
      0.21, p<.05) and NAA/Cho quotients (r=0.35, p<.001). Our results suggest that in
      AD reduced neuronal energy performance and membrane abnormalities contribute to
      metabolic deterioration.

PMID- 11328694
TI  - The modulation of late component event related potentials by pre-stimulus EEG
      theta activity in ADHD.
AB  - Electroencephalography (EEG) and Event Related Potentials (ERPs) studies in ADHD
      have generally been studied separately. This study examined these measures
      simultaneously in 54 adolescent unmedicated ADHD males and age and gender matched
      normal controls during an auditory oddball paradigm. Compared with controls, ADHD
      patients showed increased pre-stimulus EEG Theta activity and post-stimulus
      reduced N200 amplitude, increased P200 amplitude and delayed N200 and P300
      latencies evoked to target stimuli. Moreover, Theta activity was negatively
      correlated with N200 amplitude and positively correlated with P200, N200 and P300
      latency in ADHD. There were no correlations in the control group. Pre-stimulus
      preparatory state increases in Theta activity in ADHD may underlie some of the
      reported disturbances in information processing reflected in ADHD.

PMID- 11328695
TI  - The topography of quantified electroencephalography in three syndromes of
      schizophrenia.
AB  - This study investigated the association between quantified electroencephalography
      (qEEG) and three psychopathological syndromes, derived by a factor analysis of
      the symptom profile of a group of 40 subjects diagnosed with schizophrenia. An
      initial comparison with aged and sex matched normal controls showed an overall
      increase in slow wave activity in subjects with schizophrenia. The symptomatology
      of the subjects with schizophrenia was then factor analysed into three
      psychopathological syndromes that closely resembled Liddle's (1987b) original
      delineation. Correlations were undertaken between the three syndrome scores and
      qEEG. The "psychomotor poverty" factor was associated with increased beta
      activity most marked posteriorly and increased delta activity (accounted for by
      the effects of medication). The "disorganisation" factor was associated with
      widespread negative correlations in the alpha and beta bands and the "reality
      distortion" factor was associated positively with left anterior alpha activity.
      These distinct patterns of qEEG that clearly differentiate between the three
      syndromes, may contribute towards elucidating the underlying pathophysiological
      processes in schizophrenia. The results support the use of symptom based
      syndromes in reducing the diversity of findings in schizophrenia.

PMID- 11328696
TI  - Hemispheric specialization in emotion: attention, arousal, and EEG activation in
      unilateral temporal lobe epilepsy.
AB  - To investigate the neural processing of emotion in right and left temporal lobe
      epilepsy (TLE), we monitored EEG during neutral and emotionally positive and
      negative auditory stimulation. Left TLE patients displayed increased right
      lateralization and a negative emotional stimulus rating bias, while right TLE
      patients did not. This EEG arousal and negative affect may reflect deactivated
      inhibition of the right hemisphere, symptomatically expressed as arousal and
      anxiety. Failure to increase lateralization to emotional stimuli in right TLE may
      reflect compromised emotional attention/arousal centers in the right hemisphere.
      Results support a two-dimensional theory of the neural processing of emotion.

PMID- 11328697
TI  - Effects of decrease of extracellular sodium in carbachol-evoked catecholamine
      secretion in isolated adrenal medullae of rats.
AB  - The effect of extracellular Na(+) deprivation on the carbachol-evoked
      catecholamine secretion was evaluated in chromaffin cells. Isolated adrenal
      medullae of male Wistar rats were incubated in solutions with different sodium
      concentrations (144,0; 75,0; 25,0 and psi mM). Catecholamine secretions inversely
      increased as a response to fall of extracellular concentration of sodium. The
      magnitude of response to cholinergic stimulus (carbachol 100 microM) was
      decreased in low extracellular sodium concentration. Atropine (100 microM)
      inhibited secretion of catecholamine induced by carbachol in the presence and in
      the absence of extracellular sodium. Results suggest that in isolated adrenal
      medullae of rats (1) decrease in concentration of extracellular sodium increases
      secretion of catecholamines, perhaps by a greater influx of calcium from the
      extracellular environment through reversal of Na(+) /Ca(2+) exchanger; (2)
      intensity of catecholamine secretion induced by cholinergic stimulus seems to
      depend on extracellular sodium.

PMID- 11328698
TI  - The ability to smell remains intact, but does not recover, after olfactory bulb
      lesions.
AB  - We examined two unresolved issues regarding the influence of olfactory bulb
      lesions on the ability to smell. First, we asked whether the sense of smell
      remains intact or recovers after incomplete and complete removal of both
      olfactory bulbs and second, whether the qualitative perception of smell changes
      after lesion. Rats were trained to perform a four-choice olfactory discrimination
      task and were subsequently prepared with either medium, large, or complete
      bilateral olfactory bulb lesions. They were retested after a recovery period of
      either 6 or 22 weeks. The lesion effect depended on lesion size, and not on
      recovery interval. Animals with complete lesions showed no retention, and a
      failure to relearn, regardless of the recovery interval. Animals with incomplete
      lesions showed virtually perfect retention. These results, therefore, indicate
      first that the sense of smell remains intact following extensive olfactory bulb
      lesions, and that a previously acquired discrimination is permanently lost after
      complete olfactory bulb lesions.

PMID- 11328699
TI  - Contralateral rotatory bias in the free-swimming test after unilateral
      hemispherectomy in adult Swiss mice.
AB  - In the free-swimming rotatory test mice spend most of the time swimming close to
      the wall of the container attempting to escape from an aversive test situation.
      The attraction to the wall may suggest that turning behavior in the free-swimming
      test reflects the existence of intrinsic sensory asymmetries, which determine
      preferential attention adhesion to one side. In order to test this hypothesis, we
      investigated the rotatory swimming behavior of mice submitted to a unilateral
      hemispherectomy at adulthood, a condition of extreme sensory asymmetry. Fifteen
      days after surgery procedures, each mouse was tested for 5 min on 3 different
      days. We found that the hemispherectomized mice had a significant strong bias to
      turn in the direction contralateral to their lesion. These data could be
      explained considering that, in attempting to escape from the test situation,
      animals bring the recipient wall into their intact sensory field and, as a
      consequence, set the direction of locomotion. Thus, the free-swimming test may be
      useful to investigate sensory asymmetries during an aversive test situation.

PMID- 11328700
TI  - EEG beta 1 oscillation and sucrose sensitization in fibromyalgia with chemical
      intolerance.
AB  - Patients with fibromyalgia (FM) have diffuse musculoskeletal pain; half report
      concomitant intolerance for low levels of environmental chemicals (CI). Previous
      investigators have hypothesized that the chronic pain and chemical intolerance
      reflect sensitization of different central nervous system limbic and/or
      mesolimbic reward pathways. We evaluated electroencephalographic (EEG) beta
      activity and blood glucose responses of FM patients with and without CI and
      normals during three repeated sucrose ingestion sessions and during a final,
      water-only session (testing for conditioning). The FM with CI exhibited
      oscillation (reversal in direction of change from session to session) at rest and
      then sensitization (progressive amplification) of EEG beta 1 over time across the
      3 sucrose sessions versus controls. FM with CI showed sensitization of blood
      glucose over the 3 sucrose sessions, which, like the EEG findings, reverted
      toward baseline in the final water-only session. The data suggest that the subset
      of FM patients with CI have increased susceptibility to oscillation and
      physiological sensitization without conditioning, perhaps contributing to
      fluctuations in their chronic course.

PMID- 11328701
TI  - Recovery of locomotor function in adult paraplegic frogs by inductive lability in
      the distal isolated spinal cord neural networks.
AB  - We postulated (Krishnan, 1991) that in a spinal cord transected adult paraplegic
      mammal locomotor functions can be revived if polyneuronal innervation is
      reinduced in the paralyzed hind limb muscles. This procedure destabilizes the
      neural networks and induces new synaptic growth in the distal isolated cord. In
      this pilot project we tested the hypothesis in cord-transected adult paraplegic
      frogs. Polyneuronal innervation was reinduced by crushing the sciatic nerve in
      the right upper thigh. Left limb sciatic nerve was not crushed and served as
      control. Another group of adult frogs had only cord transection without nerve
      crush. Five to seven weeks postnerve crush, full powered flexion-extension
      movements in the hip and knee joints appeared in the right hind limb and were
      used for swimming and surface progression. Movements gradually declined over the
      next weeks, which in some animals was seen preserved even beyond 120 days.
      Paraplegic frogs without nerve crush did not show any recovery of locomotor
      function. Interestingly, the uncrushed contralateral limb also produced
      transient, weak locomotor-like movements. This lasted for 4 to 6 days and waned
      out completely thereafter. These results validate our hypothesis on methods to
      generate new synaptic sprouts and reconnections to redrive the locomotor system.
      We had recommended earlier that destabilization procedure should be included as
      an essential component in treatment strategies for spinal cord injury repair for
      effective relinking of the severed cord ends.

PMID- 11328702
TI  - Taurine increases rat survival and reduces striatal damage caused by 3
      nitropropionic acid.
AB  - Taurine acts as an antioxidant protecting neurons from free radical-mediated
      cellular damage. 3-nitropropionic acid (3-NP) inhibits energy metabolism,
      initiating oxidative stress. With the objective to examine whether taurine can
      protect glia and neurons from damage produced by 3-NP, male Wistar and Sprague
      Dawley rats were treated with either (1) saline, (2) taurine (3) 3-NP and saline,
      or (4) 3-NP and taurine for 4 days. Survival was determined and brains were
      processed immunohistochemically. Large striatal lesions and increased GFAP, SOD,
      and taurine immunoreactivity were detected in the 3-NP group when compared with
      control groups. In contrast, animals receiving 3-NP and taurine exhibited less
      GFAP, SOD, and taurine immunoreactivity, along with increased survival rates.
      Results indicate that taurine treatment after 3-NP administration protects the
      striatum from damage.

PMID- 11328703
TI  - Mast cell numbers in the young rat thalamus: a search for control factors.
AB  - Numbers of mast cells within brain space can be influenced by exposures to weak,
      complex magnetic fields. The present studies were designed to help isolate the
      factors that control numbers of mast cell within the thalamus (n=96) of 15 and 20
      day old rat pups. In Experiment I, rat pups were injected daily with either 1
      microliter/g or 10 microliter/g of either distilled water, isotonic saline or 0.5
      M saline; another group served as controls. The numbers of thalamic mast cells
      did not differ significantly between the four groups. In Experiment II, that
      employed a cross-fostering, split litter design, the rats whose mothers had
      consumed 0.9% taurine during pregnancy contained about twice as many mast cells
      within the thalamus compared to controls. Fifteen day old pups that had been
      reared by other mothers showed more mast cells than those reared by their own
      mothers. There were negative correlations (-.60) between the numbers of mast
      cells within the leptomeninges of the pups and the mothers' ovarian weights but
      no significant associations between the numbers of mast cells within the brains
      of the pups and the mothers.

PMID- 11328704
TI  - Suppression of analgesia in rats induced by morphine or L-NAME but not both drugs
      by microTesla, frequency-modulated magnetic fields.
AB  - In Experiment I, the nociceptive threshold for a criterion response to thermal
      stimuli (hot plate) for rats was obtained following injections with one of
      various dosages of either morphine or the nitric oxide synthase inhibitor, L
      NAME. On the bases of these results, rats in Experiment II were injected with
      either morphine (4 mg/kg), L-NAME (50 mg/kg), both morphine and L-NAME, or saline
      after baseline measurements for nociception and then exposed to either a 1
      microTesla magnetic field or to a sham field for 30 min. The magnetic field,
      presented once every 4 sec, was a frequency-modulated pattern whose pixel
      durations, for each of the 837 successive values, were 1 msec. Nociceptive
      thresholds were measured immediately after the exposure and 30 min later. The
      results indicated that exposure to this magnetic field abolished the analgesic
      effects of morphine or L-NAME when injected separately but not when injected
      together relative to rats that had received these drugs and had been exposed to
      the sham field.

PMID- 11328705
TI  - Decreased density of neurons in the medial preoptic nucleus and increased
      testicular weights for rats exposed perinatally to an 0.5 Hz Rotating Magnetic
      Field.
AB  - Pregnant Wistar rats were exposed to either 0.5 Hz Rotating Magnetic Fields (50
      microT to 300 microT or 1.5 mT to 3.0 mT) or to sham field or control
      environments for 3 days before to 3 days after the day of birth. The adult male
      offspring that had been exposed perinatally to the RMF displayed significantly
      heavier testicle weights but fewer neurons within the medial preoptic nucleus
      (MPO) and caudal ventromedial hypothalamus relative to sham field controls
      (effect size about 30%). There was no statistically significant difference
      between the two ranges of RMF intensities for these measures. RMF-exposed rats
      relative to sham-field exposed rats did not differ with respect to spleen
      weights, body weights, or mounting (reproductive) activity. The heavier testicle
      weights replicated previous studies and suggest that permanent, selective
      alterations in neuronal density can also occur subsequent to perinatal exposure
      to relatively weak, extremely low frequency magnetic fields.

PMID- 11328706
TI  - Neuroblastoma cell lines--a versatile in vitro model in neurobiology.
AB  - Neuroblastoma (NB) cell lines are transformed, neural crest derived cells,
      capable of unlimited proliferation in vitro. These cell lines retain the ability
      of differentiation into neuronal cell types on treatment with various agents.
      This ability of NB cells to proliferate as well as to differentiate makes it an
      excellent in vitro system for various studies. This review article focuses on the
      applications and potential uses of murine and human NB cell lines. NB cells are
      extensively used for testing neurotoxicity of putative drugs such as antimalarial
      or anticancer agents. NB cell lines have wide applications in virus research to
      understand various aspects of virus-host cell interactions at the molecular and
      cellular levels. They have been used to dissect the relationships between
      proliferation, differentiation and apoptosis. This feature has been useful in
      understanding the pediatric cancer--neuroblastoma and for development of newer
      therapies.

PMID- 11328707
TI  - Effect of local synaptic strengthening on global activity-wave growth in the
      hippocampus.
AB  - Analysis of a continuum model of the hippocampus shows that strengthening of the
      synaptic connections within localized regions can convert the global activity
      wave properties from decay to growth. These growing waves can play a part in the
      implantation of long-term memory in the higher brain regions. The wavelength of
      the fastest-growing mode decreases with increasing local synaptic strength and
      can be modified by the chemical state as reflected by synaptic sensitivity to
      stimuli. The temporal period of the response is a constant, equal to twice the
      delay time exhibited by some of the hippocampal inhibitory neurons ("d-cells").
      The value for the period obtained from this relationship and measurement of the
      delay time agrees with the hippocampal gamma rhythm. For normal hippocampal
      function the proportion of d-cells is limited to one-third the total number of
      inhibitory neurons.

PMID- 11328708
TI  - An ab initio investigation of 2-amino-2-imidazoline: a key moiety in chemical and
      biochemical processes.
AB  - The 2-amino-2-imidazoline moiety is currently used not only in drugs, but also in
      insecticides, and fungicides. Ab initio calculations are performed to evaluate
      the molecular properties of the two tautomeric forms and the protonated form with
      extended basis sets ranging from 6-31G* to 6-311++G** at Hartree-Fock and density
      functional (BLYP and B3LYP) levels. Moller-Plesset perturbation is tested at the
      MP2/6-31G* level only. Optimized geometry structures, energies and thermochemical
      properties are generated. Basis set and correlation effects on geometries,
      tautomer equilibrium constant and protonation enthalpy are carefully analysed.
      Although observed for the isolated molecule, these results may be extrapolated to
      chemical and biochemical systems of interest.

PMID- 11328709
TI  - Physicochemical and graph theoretical descriptors in developmental toxicity SAR:
      a comparative study.
AB  - Chemical insults to the developing fetus can lead to growth retardation,
      malformation, death, and functional deficits. The present study seeks to
      determine if physicochemical and/or graph theoretical parameters can be used to
      determine a structure-activity relationship (SAR) for developmental toxicity, and
      if consistency is observed among the selected features. The biological data
      utilized consists of a diverse series of compounds evaluated within the Chernoff
      Kavlock in vivo mouse assay. Physicochemical parameters calculated correspond to
      electronic, steric, and transport properties. Graph theoretical parameters
      calculated include the simple, valence, and kappa indices. Both sets of
      parameters were independently applied to derive SARs in order to compare the
      quality of the respective models. Multiple random sampling, without replacement,
      was utilized to obtain ten training/test partitions. Models were built by linear
      discriminant analysis, decision trees, and neural networks respectively.
      Comparisons on identical sets of data were carried out to determine if any of the
      model building procedures had a significant advantage in terms of predictive
      performance. Furthermore, comparison of the features selected within and across
      the model building processes led to the determination of model consistency. Our
      results indicate that consistent features related to developmental toxicity are
      observed and that both physicochemical and graph theoretical parameters have
      equal utility.

PMID- 11328710
TI  - Molecular similarity based estimation of properties: a comparison of structure
      spaces and property spaces.
AB  - Molecular similarity methods have emerged as powerful tools in analog selection,
      chemical classification based on toxic modes of action, and property estimation.
      The basic assumption of structure-activity relationships (SAR) is that similar
      structures usually have similar properties. Therefore, similarity methods can be
      used for the selection of analogs and estimation of properties of chemicals from
      their structural analogs in property spaces. Each similarity method is user
      defined. Its efficacy depends on the set of descriptors used to define the
      intermolecular similarity of chemicals as well as on the mathematical function
      used to quantify similarity. Also, similarity methods can be based on
      experimental data or computed molecular descriptors. We have carried out a
      comparative study of similarity spaces derived from experimental data vis-a-vis
      computed structural parameters for two sets of chemicals: (a) a diverse set of 76
      chemicals derived from the TSCA Inventory and (b) the 166 structurally distinct
      constituents of JP-8 identified by GC/MS. Property spaces for these two sets of
      chemicals were created using experimental and calculated physicochemical
      properties. Atom pairs (APs) and topological indices calculated by POLLY v2.3
      were used to create theoretical structure spaces. These spaces were used for the
      KNN-based estimation of properties with K=1--10, 15, 20, 25. The results will be
      presented with a comparative analysis of the effectiveness of property spaces and
      structure spaces in analog selection and property estimation.

PMID- 11328711
TI  - Structures and electron attachment properties of halomethanes (CX(n)Y(m), X=H, F;
      Y=Cl, Br, I; n=0,4; m=4-n).
AB  - Theoretical studies of structures of neutral molecules and their anions as well
      as dissociative electron attachment properties are presented for the halomethanes
      of general formula CX(n) Y(m); X=H, F; Y=Cl, Br, I; n=0,4; m=4-n. The
      dissociative electron attachment seems to be the primary process resulting in
      toxicity of these species. The halomethane anions containing hydrogens are formed
      as radical-anion adducts. When H is replaced by F, these species become true
      sigma* radicals. The electron affinities are computed using a variety of
      computational techniques including the four-order Moller-Plesset (MP4) technique
      that included 250 basis functions. It is challenging to compare the computed
      results with experiment due to dearth of experimental data and uncertainties in
      the existing experimental data. Thus in certain cases larger differences are
      found between the computed and experimental values.

PMID- 11328712
TI  - A general QSAR model for predicting the acute toxicity of pesticides to Lepomis
      macrochirus.
AB  - A Quantitative Structure-Activity Relationship (QSAR) model was derived for
      estimating the acute toxicity of pesticides against Lepomis macrochirus under
      varying experimental conditions. Chemicals were described by means of
      autocorrelation descriptors encoding lipophilicity (H(0) to H(5)) and the H
      bonding acceptor ability (HBA(0)) and H-bonding donor ability (HBD(0)) of the
      pesticides. A three-layer feedforward neural network trained by the back
      propagation algorithm was used as statistical engine for deriving a powerful QSAR
      model accounting for the weight of the fish, time of exposure, temperature, pH,
      and water hardness.

PMID- 11328713
TI  - Quantitative structure-retention relationships for gas chromatographic retention
      indices of alkylbenzenes with molecular graph descriptors.
AB  - Quantitative structure-retention relationships (QSRR) represent statistical
      models that quantify the connection between the molecular structure and the
      chromatographic retention indices of organic compounds, allowing the prediction
      of retention indices of novel, not yet synthesized compounds, solely from their
      structural descriptors. Using multiple linear regression, QSRR models for the gas
      chromatographic Kovats retention indices of 129 alkylbenzenes are generated using
      molecular graph descriptors. The correlational ability of structural descriptors
      computed from 10 molecular matrices is investigated, showing that the novel
      reciprocal matrices give numerical indices with improved correlational ability. A
      QSRR equation with 5 graph descriptors gives the best calibration and prediction
      results, demonstrating the usefulness of the molecular graph descriptors in
      modeling chromatographic retention parameters. The sequential orthogonalization
      of descriptors suggests simpler QSRR models by eliminating redundant structural
      information.

PMID- 11328714
TI  - QSAR for acetylcholinesterase inhibition and toxicity of two classes of
      phosphoramidothioates.
AB  - Methamidophos (Met) is a weak inhibitor of housefly head AChE but at the same
      time it is highly toxic to the common housefly. The lethality of Met is believed
      to be due to AChE inhibition. An extensive QSAR study may help in determining the
      mode of action of Met in vivo and in vitro and provide a rational for its high
      insecticidal toxicity. Acephate (Ace), like Met, is a poor inhibitor of AChE in
      vitro and has a comparable to Met insect toxicity in vivo. Contrary to Met,
      though, Ace has much lower mammalian toxicity. Understanding the structural
      properties which make insecticides toxic to insects but not to mammals is of
      great importance, since mammals (including humans) are inadvertently exposed to
      these compounds. Our results were consistent with the model in which both the in
      vitro and in vivo toxicity of Met depends on the inhibition of the active center
      of AChE by the unchanged Met. An optimal susceptibility to hydrolysis is needed
      for Met and its analogs to have high insecticidal activity since in order to
      phosphorylate AChE they need to be hydrolyzed and at the same time their
      stability is of great importance in vivo for accumulating at the site of action.
      The insecticidal activity of Ace analogs may be due to direct interaction with
      the active center of the AChE. The mammalian toxicity of Ace analogs may be due
      to interaction with an 'allosteric' reaction center in the AChE.

PMID- 11328715
TI  - The use of Hasse diagrams as a potential approach for inverse QSAR.
AB  - Quantitative structure-activity relationships are often based on standard
      multidimensional statistical analyses and sophisticated local and global
      molecular descriptors. Here, the aim is to develop a tool helpful to define a
      molecule or a class of molecules which fulfills pre-described properties, i.e.,
      an Inverse QSAR approach. If highly sophisticated descriptors are used in QSAR,
      the structure and then the synthesis recipe may be hard to derive. Thus,
      descriptors, from which the synthesis recipe can be easily derived, seem
      appropriate to be included within this study. However, if descriptors simple
      enough to be useful for defining syntheses recipes of chemicals were used, the
      accuracy of a numeric expression may fail. This paper suggests a method, based on
      very simple elements of the theory of partially ordered sets, to find a
      qualitative basis for the relationship between such fairly simple descriptors on
      the one side and a series of ecotoxicological properties, on the other side. The
      partial order ranking method assumes neither linearity nor certain statistical
      distribution properties. Therefore the method may be more general compared to
      many standard statistical techniques. A series of chlorinated aliphatic compounds
      has been used as an illustrative example and a comparison with more sophisticated
      descriptors derived from quantum chemistry and graph theory is given. Among the
      results, it was disclosed that only for algae lethal concentration, as one of the
      four ecotoxicological properties, the synthesis specific predictors seem to be
      good estimators. For all other ecotoxicological properties quantum chemical
      descriptors appear as the more suitable estimators.

PMID- 11328716
TI  - Structure-toxicity analyses of Tetrahymena pyriformis exposed to pyridines -- an
      examination into extension of surface-response domains.
AB  - A selection of mechanistically diverse substituted pyridines were tested in the
      Tetrahymena pyriformis population growth impairment assay. The response-surface
      approach was used to derive multiple-regression type structure-toxicity
      relationships between T. pyriformis population growth impairment toxicity data
      (log(IGC(-1)(50)) and the 1-octanol/water partition coefficient (log K(ow)) and
      one of two different descriptors of molecular orbital interaction: energy of the
      lowest unoccupied molecular orbital (E(LUMO)) and maximum acceptor
      superdelocalizability (S(MAX)). A statistically robust model (log(IGC(-1)(50)) = 
      3.91 + 0.50(logK(ow)) + 10.70(S(MAX)); n=83, r(2) =0.756, s=0.38, F=124,
      Pr>F=0.0001) was developed with S(MAX) as the indicator of reactivity. This model
      was not statistically different in fit from the model (log(IGC(-1)(50)) = -1.19 =
      0.56(logK(ow)) - 0.61(E(LUMO)); n=86, r(2) =0.749, s=0.38, F=124, Pr>F=0.0001)
      derived using the alternative descriptor of electrophilic interaction. Compounds
      with high residual values were removed. An examination of these outliers from
      both response-surfaces, revealed that pyridines substituted in the 2-position
      with electron-releasing groups and halogenated nitro-substituted pyridines did
      not fit the above models well. A third group of outliers, the mono-halogenated
      pyridines, was unique to the S(MAX) response-surface, which are neutral narcotics
      with potentially high volatility. A comparison of observed and predicted
      toxicities for a validation set of pyridines for the S(MAX) surface (log(observed
      IGC(-1)(50) = 0.10 + 0.75(log(predicted IGC(-1)(50)); n=10, r(2) =0.662, s=0.49,
      F=15.7, Pr>F=0.004) and the E(LUMO) surface (log(observed IGC(-1)(50)) = 0.17 +
      0.80(log(predicted IGC(-1)(50)); n=10, r(2) =0.707, s=0.45, F=19.3, Pr>F=0.002)
      validated the above models, with the fit in the same range as the parent model.
      The model derived with S(MAX) was compared to the response-surface derived for
      substituted benzenes (log(IGC(-1)(50)) = -3.47 + 0.50(logK(ow)) + 9.85(S(MAX));
      n=197, r(2) =0.816, s=0.34, F=429, Pr>F=0.0001) revealing the similarities in
      slope and intercept between the two response-surfaces. The model fit was poorer
      for the pyridine surface, which may be a factor of increased reactivity due to
      the presence of nitrogen and the associated pair of unshared electrons in the
      ring not present in benzene. However, the similarity of the pyridine and benzene
      response-surfaces suggests that the domain defined for benzenes may be extended
      to encompass nitrogen heterocyclic pyridines.

PMID- 11328717
TI  - Introducing Laszlo Bito and Johan Stjernschantz, the 2000 recipients of the
      Proctor Medal.

PMID- 11328718
TI  - A new approach to the medical management of glaucoma, from the bench to the
      clinic, and beyond: the Proctor Lecture.

PMID- 11328719
TI  - From PGF(2alpha)-isopropyl ester to latanoprost: a review of the development of
      xalatan: the Proctor Lecture.

PMID- 11328720
TI  - Continuous ambient lighting and eye growth in primates.
AB  - PURPOSE: To determine the effect of continuous light exposure on ocular growth
      and emmetropization in infant monkeys. METHODS: Nine infant rhesus monkeys were
      reared with the normal vivarium lights on continuously. The 24-hour light cycle
      was initiated between 1 and 4 weeks of age and maintained for 6 months. The
      ocular effects of continuous light were assessed by cycloplegic retinoscopy,
      keratometry, and A-scan ultrasonography. Longitudinal control data were obtained
      from 23 normal infants that were reared with an illumination cycle that included
      defined light and dark phases (either 12-hour light:12-hour dark or 8.5-hour
      light:15.5 hour dark). RESULTS: In contrast to previous studies involving light
      reared chickens, no monkeys exhibited exaggerated ocular growth. There were no
      significant differences between treated and control monkeys in corneal radius,
      overall eye size, or the axial dimensions of individual ocular components. At the
      end of the treatment period, eight of the nine experimental monkeys also
      exhibited the moderate hyperopic errors (range, +1.5 to +3.4 D) that are
      typically found in normal animals. Aspects of emmetropization were, however,
      unusual for three monkeys. One monkey manifested a -0.50 D myopic error that was
      associated with an abnormally steep cornea but had normal axial lengths. Two
      additional monkeys developed persistent axial anisometropias. CONCLUSIONS: In
      infant primates constant light exposure does not promote the constellation of
      ocular changes (in particular corneal flattening, a decrease in anterior chamber
      depth, and an increase in vitreous chamber depth) that has been observed in light
      reared chickens. The slight variations from the expected developmental sequence
      observed in three infants may reflect individual differences. However, it is also
      possible that aspects of the emmetropization process may not operate as
      effectively under constant light as they do under an ordinary light/dark cycle.

PMID- 11328721
TI  - Steady state mRNA levels in tree shrew sclera with form-deprivation myopia and
      during recovery.
AB  - PURPOSE: In tree shrews, visual form deprivation induces myopia and tissue
      remodeling in the sclera, characterized by decreased levels of collagen and
      glycosaminoglycans (GAGs) and increased levels of matrix metalloproteinases
      (MMPs). Removal of the visual deprivation allows recovery. This study
      investigated whether these changes are accompanied by changes in steady state
      mRNA levels in the sclera. METHODS: Quantitative competitive reverse
      transcription-polymerase chain reaction (RT-PCR) was used to measure steady state
      levels of mRNA for collagen (alpha1(I) chain), decorin (core protein), gelatinase
      A (MMP-2), stromelysin-1 (MMP-3), and a tissue inhibitor of metalloproteinase
      (TIMP-1) in the scleras of tree shrews that received either 11 days of monocular
      form deprivation (MD) or 11 days of MD followed by 4 days of recovery. A group of
      age-matched normal animals was also measured. RESULTS: After 11 days of MD,
      alpha1(I) collagen mRNA levels were 34% lower, and MMP-2 mRNA levels were 66%
      higher in the deprived eyes than in the control eyes. After 4 days of recovery,
      collagen mRNA levels were 33% higher, MMP-2 levels were 20% lower, and TIMP-1
      levels were 43% higher in the recovering eyes than in the control eyes. Decorin
      and MMP-3 mRNA levels were not significantly different between the treated and
      control eyes after MD or after recovery. CONCLUSIONS: The tissue remodeling in
      mammalian sclera induced by altering the visual environment is accompanied by
      modulation of mRNA levels in the sclera. The levels of collagen and MMP-2 mRNA
      were modulated in a pattern generally consistent with observed changes in protein
      levels, suggesting that visual regulation of the levels of these scleral proteins
      may involve modulation of gene expression at the transcriptional level.

PMID- 11328722
TI  - Uveal melanoma: mean of the longest nucleoli measured on silver-stained sections.
AB  - PURPOSE: To summarize and compare the various histologic methodologies for using
      nucleoli to assess the malignant potential of uveal melanoma. METHODS: This was
      an observational series of 100 samples of uveal melanoma in which histologic
      sections were studied. The cases were selected so that approximately half (n =
      49) of the tumors were from patients who had died of metastatic malignant
      melanoma. The 51 remaining tumors were from patients who had survived at least 9
      years without development of metastasis. Central sections from the uveal
      melanomas were stained using the colloidal silver nitrate stain for nucleolar
      organizing regions (AgNOR). These were compared with an adjacent hematoxylin and
      eosin (H&E)-stained section. A light microscope with a micrometer inset into the
      eyepiece (x10) was used at a final magnification of x1000 under oil immersion to
      measure the length of the nucleolus along the longest axis and the width
      perpendicular to that axis. From at least twenty cells selected from random
      fields throughout the tumor, the mean of the 10 longest and widest nucleoli (MLN)
      was calculated. Seven samples had to be discarded because the nucleoli were
      unmeasurable. RESULTS: T-tests and Cox proportional hazard regression analysis
      indicated that the MLN of nucleolar length as measured on AgNOR-stained slides
      was as significant as cell type but was more significant than other
      histopathologic prognosticating variables measured and evaluated in this study.
      These prognosticators included tumor size, calculated as the largest tumor
      dimension; MLN width; and MLN length, as measured on H&E-stained sections.
      CONCLUSIONS: It has previously been demonstrated that AgNOR-stained nucleoli,
      unlike H&E-stained nucleoli, can be captured and measured by an automated image
      analyzer with prognostically significant results. This new method of simple oil
      immersion measurements of the longest AgNOR-stained nucleoli length in
      microscopic sections of uveal melanoma provides an inexpensive and highly
      significant method for predicting outcome in patients with uveal melanoma.
      Because of the high contrast with the background, the silver-stained nucleoli
      clearly define the nucleolar boundaries, rendering them readily discernible and
      allowing greater ease and speed of measurement when compared with H&E-stained
      nucleoli. The method of random sampling that was used was comparable with linear
      sampling in predicting outcome. Highly necrotic tumors, however, had to be
      excluded from the study because of loss of nucleolar morphology.

PMID- 11328723
TI  - 16S rDNA-based identification of bacteria from conjunctival swabs by PCR and DGGE
      fingerprinting.
AB  - PURPOSE: Establishment of a new molecular biology technique for the
      identification of multiple bacteria from the ocular environment, which can be
      applied supplementarily to cultivation in cases of severe bacterial infections.
      METHODS: From 60 human conjunctivae (29 with purulent and 31 with nonpurulent
      conjunctivitis), swabs were taken and DNA was extracted. Fragments of 200 bp,
      spanning the V3 region of the eubacterial 16S rDNA, were amplified by polymerase
      chain reaction (PCR) and separated by denaturing gradient gel electrophoresis
      (DGGE). For phylogenetic identification, DGGE bands were excised and directly
      sequenced, or 16S rDNA clone libraries were constructed and clones were screened
      by DGGE. Sequences were compared with sequences of known bacteria listed in the
      EMBL database. Furthermore, the results were compared with results obtained from
      conventional cultivation. RESULTS: 16S rDNA could be amplified from 25 of 29
      investigated swabs taken from purulent conjunctivitis eyes and from 2 of 31
      investigated swabs taken from nonpurulent conjunctivitis eyes. Sixteen samples
      showed monomicrobial and 11 samples showed polymicrobial infections. The
      following genera (n is number of samples) were detected: Staphylococcus (n = 8),
      Corynebacterium (n = 7), Propionibacterium (n = 7), Streptococcus (n = 6),
      Bacillus (n = 2), Acinetobacter (n = 3), Pseudomonas (n = 3), Proteus (n = 1),
      and Brevundimonas (n = 1). Four sequences could not be identified to the genus
      level. They had highest sequence similarities both to sequences of Pantoea and
      Enterobacter (n = 1), Kingella and Neisseria (n = 1), Serratia and Aranicola (n =
      1), and Leuconostoc and Weissella (n = 2), respectively. Culture was only
      positive for coagulase-negative staphylococci (n = 9), Corynebacteria (n = 3),
      Staphylococcus aureus (n = 1), Streptococcus sp. (n = 1), Proteus sp. (n = 1),
      Klebsiella oxytoca (n = 1), and Pseudomonas aeruginosa (n = 1). In total, 45% of
      the 60 analyzed conjunctival swabs were PCR positive, whereas only 22% were
      culture positive. No sample positive by culture gave negative results by PCR.
      CONCLUSIONS: 16S rDNA sequence analyses and DGGE fingerprinting are appropriate
      methods for the detection and identification of monomicrobial as well as
      polymicrobial ocular infections of bacteria that might not be detected by
      conventional cultivation.

PMID- 11328724
TI  - Colocalization of neuropilin-1 and Flk-1 in retinal neovascularization in a mouse
      model of retinopathy.
AB  - PURPOSE: To investigate the mechanisms of the development of retinal
      neovascularization, the localizations of vascular endothelial (VEGF) receptors
      Flk-1 and neuropilin (NP)-1 mRNAs were examined. METHODS: The model of
      retinopathy of prematurity (ROP) was produced by ischemia-induced ocular
      neovascularization, by exposing postnatal day-7 mice to 75% oxygen for 5 days and
      then returning them to room air for 5 days. Retinal neovascularization was
      visualized by injection of fluorescein-dextran. Expression of Flk-1 and NP-1
      mRNAs were examined by in situ hybridization with flatmount and serial sections
      of the retina. The localization of NP-1 was also confirmed by
      immunohistochemistry. Blood vessel patterns were characterized by
      immunohistochemical localization of von Willebrand factor (vWF). RESULTS:
      Flatmount in situ hybridization showed intense expression of NP-1 and Flk-1 mRNAs
      colocalized in the area of neovascularization. In situ hybridization of serial
      sections of the retina revealed that expression of Flk-1 and NP-1 was restricted
      to neovascularized vessels of the retina from ROP mice. CONCLUSIONS: The
      restricted expression of Flk-1 and NP-1 on neovascularized vessels suggests that
      these molecules may play important roles in retinal neovascularization. This is
      the first report of the colocalization of NP-1 and Flk-1 on neovascularized
      vessels of the retina from ROP mice.

PMID- 11328725
TI  - An analysis of allelic variation in the ABCA4 gene.
AB  - PURPOSE: To assess the allelic variation of the ATP-binding transporter protein
      (ABCA4). METHODS: A combination of single-strand conformation polymorphism (SSCP)
      and automated DNA sequencing was used to systematically screen this gene for
      sequence variations in 374 unrelated probands with a clinical diagnosis of
      Stargardt disease, 182 patients with age-related macular degeneration (AMD), and
      96 normal subjects. RESULTS: There was no significant difference in the
      proportion of any single variant or class of variant between the control and AMD
      groups. In contrast, truncating variants, amino acid substitutions, synonymous
      codon changes, and intronic variants were significantly enriched in patients with
      Stargardt disease when compared with their presence in subjects without Stargardt
      disease (Kruskal-Wallis P < 0.0001 for each variant group). Overall, there were
      2480 instances of 213 different variants in the ABCA4 gene, including 589
      instances of 97 amino acid substitutions, and 45 instances of 33 truncating
      variants. CONCLUSIONS: Of the 97 amino acid substitutions, 11 occurred at a
      frequency that made them unlikely to be high-penetrance recessive disease-causing
      variants (HPRDCV). After accounting for variants in cis, one or more changes that
      were compatible with HPRDCV were found on 35% of all Stargardt-associated alleles
      overall. The nucleotide diversity of the ABCA4 coding region, a collective
      measure of the number and prevalence of polymorphic sites in a region of DNA, was
      found to be 1.28, a value that is 9 to 400 times greater than that of two other
      macular disease genes that were examined in a similar fashion (VMD2 and EFEMP1).

PMID- 11328726
TI  - Complete abolition of the retinal-specific guanylyl cyclase (retGC-1) catalytic
      ability consistently leads to leber congenital amaurosis (LCA).
AB  - PURPOSE: Leber congenital amaurosis (LCA) is the earliest and the most severe
      form of all inherited retinal dystrophies. In 1996, the current investigators
      ascribed the disease in families linked to the LCA1 locus on chromosome 17p13.1
      to mutations in the photoreceptor-specific guanylyl cyclase (retGC-1) gene. So
      far, 22 different mutations, of which 11 are missense mutations, have been
      identified in 25 unrelated families. This is a report of the functional analyses
      of nine of the missense mutations. METHODS: cDNA constructs were generated that
      contained the retGC-1 missense mutations identified in patients related to the
      LCA1 locus. Mutants were expressed in COS7 cells and assayed for their ability to
      hydrolyze guanosine triphosphate (GTP) into cyclic guanosine monophosphate
      (cGMP). RESULTS: All mutations lying in the catalytic domain showed a complete
      abolition of cyclase activity. In contrast, only one mutation lying in the
      extracellular domain also resulted in a severely reduced catalytic activity,
      whereas the others showed completely normal activity. CONCLUSIONS: More than half
      the mutations identified in patients related to the LCA1 locus are truncating
      mutations expected to result in a total abolition of retGC-1 activity. Concerning
      missense mutations, half of them lying in the catalytic domain of the protein
      also result in the complete inability of the mutant cyclases to hydrolyze GTP
      into cGMP in vitro. In contrast, missense mutations lying in the extracellular
      domain, except one affecting the initiation codon, showed normal catalytic
      activity of retGC-1. Nevertheless, considering that all patients related to the
      LCA1 locus displayed the same phenotype, it can be assumed that all missense
      mutations would have the same dramatic consequences on protein activity in vivo
      as truncation mutations.

PMID- 11328727
TI  - Expression and localization of angiogenic inhibitory factor, chondromodulin-I, in
      adult rat eye.
AB  - PURPOSE: To determine the role in the eye of chondromodulin (ChM)-I, which has
      been identified in cartilage as an angiogenic inhibitor, the expression and
      localization and a possible function of ChM-I were investigated. METHODS:
      Expression and localization of ChM-I in rat eyes were examined by RNase
      protection assay and in situ hybridization and by immunostaining, using an
      antibody against a synthetic peptide. The effect of recombinant ChM-I on tube
      morphogenesis of retinal endothelial cells was examined in culture. RESULTS: The
      rat ChM-I gene was determined to encode the open reading frame of 334 amino acid
      residues, and ChM-I mRNA was exclusively expressed in cartilage, eye, and
      cerebellum in rats. ChM-I mRNA expression was evident in the iris-ciliary body,
      retina, and scleral compartments, but not in other compartments of the eye. In
      situ hybridization revealed mRNA expression in the ganglion cells, inner nuclear
      layer cells, and pigment epithelium in the retina and in the nonpigment
      epithelium of the ciliary body. Immunoreactive ChM-I was present in these cells
      and also in the vitreous body. Western blot analysis detected an approximately 25
      kDa band of ChM-I presumed as a secretory form in the aqueous humor and vitreous
      body and an approximately 37-kDa band as a precursor form in the retina.
      Recombinant human ChM-I inhibited tube morphogenesis of human retinal endothelial
      cells in vitro. CONCLUSIONS: These observations indicate a potential role for ChM
      I in inhibition of angiogenesis in the rat eye.

PMID- 11328728
TI  - Production of prostaglandin D synthase as a keratan sulfate proteoglycan by
      cultured bovine keratocytes.
AB  - PURPOSE: To characterize the major proteoglycans produced and secreted by
      collagenase-isolated bovine keratocytes in culture. METHODS: Freshly isolated
      keratocytes from mature bovine corneas were cultured in serum-free Dulbecco's
      modified Eagle's medium/ F12. Secreted proteoglycans were radiolabeled with
      protein labeling mix ((35)S-Express; Dupont NEN Life Science Products, Boston,
      MA) and digested with chondroitinase ABC, keratanase, and endo-beta-galactosidase
      to remove glycosaminoglycan chains, and core proteins were analyzed by
      autoradiography and Western blot analysis. An unidentified keratan sulfate
      proteoglycan (KSPG) was purified by gel filtration (Superose 6; Amersham
      Pharmacia, Piscataway, NJ) and anion-exchange chromatography (Resource Q;
      Amersham Pharmacia) and subjected to amino acid sequencing. RESULTS: Keratanase
      digestion of proteoglycans produced approximately 50 kDa core proteins that
      immunoreacted with antisera to lumican, keratocan, and osteoglycin-mimecan.
      Chondroitinase ABC digestion produced a approximately 55-kDa core protein that
      immunoreacted with antisera to decorin. A 28-kDa band generated by keratanase or
      endo-beta-galactosidase digestion did not react with these antibodies.
      Chromatographic purification and amino acid sequencing revealed that the protein
      was prostaglandin D synthase (PGDS). Identity was confirmed by Western blot
      analysis using antisera to recombinant PGDS. PGDS isolated from corneal extracts
      was not keratanase sensitive but was susceptible to endo-beta-galactosidase,
      suggesting that it contains unsulfated polylactosamine chains in native tissue
      and is therefore present as a glycoprotein. CONCLUSIONS: These results indicate
      that bovine keratocytes, when cultured under serum-free conditions, produce the
      four known leucine-rich proteoglycans decorin, keratocan, lumican, and
      osteoglycin/mimecan and maintain a phenotype that is comparable to that of in
      situ keratocytes. Additionally, these cells produce PGDS, a known retinoid
      transporter, as a KSPG.

PMID- 11328729
TI  - Segregation patterns and heteroplasmy prevalence in Leber's hereditary optic
      neuropathy.
AB  - PURPOSE: To investigate the segregation pattern of the mitochondrial DNA mutation
      at nucleotide position 3460 responsible for Leber's hereditary optic neuropathy
      (LHON) and to determine the prevalence of heteroplasmy for the three primary LHON
      mutations at positions 11778, 3460, and 14484. METHODS: Segregation analysis was
      performed in a cross-sectional study by determining the level of heteroplasmy in
      blood leukocytes of 23 LHON patients and unaffected carriers from four unrelated
      families. One family comprising two affected and three unaffected carriers was
      followed over 5.5 years for a longitudinal segregation analysis of heteroplasmy.
      The percentage of mutant mtDNA was determined using a novel procedure of
      fluorescence-based primer extension and restriction fragment length polymorphism
      analysis. The prevalence of heteroplasmy was assessed by determining the number
      of genealogically unrelated LHON pedigrees with heteroplasmic maternal family
      members from the LHON patient records of the Department of Ophthalmology,
      University of Tubingen, Germany. RESULTS: The authors observed a marked
      variability in the degree of heteroplasmy levels within each pedigree and a
      tendency toward a higher mutant allele frequency in offspring generations.
      Disease expression was correlated with higher levels of mutant mtDNA molecules.
      Longitudinal analysis revealed no statistically significant decrease in the
      heteroplasmy level in the family studied but a reduction of 11% and 12% in one
      affected and one unaffected individual, respectively. In 167 genealogically
      unrelated LHON families the prevalence of heteroplasmy was 5.6%, 40%, and 36.4%
      for the 11778, 3460, and 14484 LHON mutations, respectively. CONCLUSIONS: Cross
      sectional studies of heteroplasmy for the 3460 LHON mutation suggest that the
      genotype shifts toward a higher mutational load in offspring generations. Long
      term decrease in the blood mutant load in single cases indicates negative
      selection of the mutant allele in the hematopoietic cell system. The prevalence
      of heteroplasmy varies significantly between the different primary LHON
      mutations, suggesting genotypical differences in disease expression.

PMID- 11328730
TI  - The development of the Melbourne low-vision ADL index: a measure of vision
      disability.
AB  - PURPOSE: To develop a new test of activities of daily living (ADLs) appropriate
      for the low-vision population: the Melbourne Low-Vision ADL Index (MLVAI).
      METHODS: The MLVAI was designed as a desk-based clinical assessment, comprising
      18 observed items on complex ADLs in part (a) and 9 questions on broad self-care
      ADLs in part (b). Each item was rated on a five-level descriptive scale from 0 to
      4, based on independence, speed, and accuracy of performance. It was designed to
      be administered under standardized conditions with regard to the instructions,
      illumination, and working distances. The validity and reliability of the new
      MLVAI was determined for 122 subjects who were representative of the general low
      vision population, in a cross-sectional study. RESULTS: Two items were found to
      be redundant and were eliminated from the test. Thus, the final test comprised 25
      items, with 100 being the highest possible score. Cronbach's alpha indicated an
      internal reliability of 0.96, and an intraclass correlation coefficient indicated
      an overall reliability of 0.95. The SE of measurement was 4.5. According to
      Spearman's correlation coefficient, the test-retest reliability was 0.94 (P <
      0.001), and the interpractitioner reliability for five different pairs of
      practitioners was 0.90 or higher (P < 0.001). With regard to validity, there was
      a moderately high correlation with vision impairment (r = -0.68, P < 0.001).
      Using Rasch analysis, content validity was also demonstrated by good separation
      indexes (4.70 and 9.88) and high reliability scores (0.96 and 0.99) for the
      person and items parameters, respectively. Separate calculation of indexes and
      reliability scores for parts (a) and (b) indicated high content validity and
      reliability of each part. However, the separation indexes and reliability scores
      were higher for part (a) than for part (b). The correlation coefficient for part
      (a) and part (b) was 0.68. CONCLUSIONS: The MLVAI is a highly valid and reliable
      standardized test of ADL performance for the general low-vision population. It
      may be used to assess patients with low vision and has the potential to be used
      as a measure of low-vision rehabilitation outcomes.

PMID- 11328731
TI  - ETDRS-fast: implementing psychophysical adaptive methods to standardized visual
      acuity measurement with ETDRS charts.
AB  - PURPOSE: To measure visual acuity (VA) on Early Treatment Diabetic Retinopathy
      Study (ETDRS) charts with a modified faster procedure (ETDRS-Fast), based on
      adaptive psychophysics methods and to assess the method's validity and
      reproducibility. METHODS: Whereas the standard method for measuring VA with the
      ETDRS charts requires that the subject read all the letters beginning with the
      top row, in the ETDRS-Fast procedure, the subject is asked to read only one
      letter per row until a mistake is made. Then, following simple rules, the
      examiner finds a row from which the subject can begin reading all the letters
      downward, thus making the method identical with the standard method near
      threshold. VA determination was performed twice with both methods in 57 subjects
      in two separate sessions to assess validity and reproducibility. RESULTS: In both
      sessions the correlation between the two procedures was high (intraclass
      correlation coefficient 0.95), confirming the validity of the ETDRS-Fast
      procedure. Reproducibility was good for both procedures, with intraclass
      correlation coefficients of 0.94 for the standard and 0.96 for the ETDRS-Fast
      method. The ETDRS-Fast procedure allowed a significantly shorter test duration (
      30%; P < 0.0001). CONCLUSIONS: Adaptive procedures allow accurate and fast
      determination of psychophysical thresholds by reducing the number of stimulus
      presentations when the subject is far from threshold. In the ETDRS-Fast method a
      few simple rules applied to optotype chart reading allow adaptation to each
      patient's level of VA. The ETDRS-Fast procedure significantly reduces test time
      and still yields results that are as accurate as those obtained with the standard
      method.

PMID- 11328732
TI  - Genes and environment in refractive error: the twin eye study.
AB  - PURPOSE: A classical twin study was performed to examine the relative importance
      of genes and environment in refractive error. METHODS: Refractive error was
      examined in 226 monozygotic (MZ) and 280 dizygotic (DZ) twin pairs aged 49 to 79
      years (mean age, 62.4 years). Using a Humphrey-670 automatic refractor,
      continuous measures of spherical equivalent, total astigmatism, and corneal
      astigmatism were recorded. Univariate and bivariate maximum likelihood model
      fitting was used to estimate genetic and environmental variance components using
      information from both eyes. RESULTS: For the continuous spectrum of
      myopia/hyperopia, a model specifying additive genetic and unique environmental
      factors showed the best fit to the data, yielding a heritability of 84% to 86%
      (95% confidence interval [CI], 81%-89%). If myopia and hyperopia (< or = -0.5 D
      and > or = 0.5 D, respectively) were treated as binary traits, the heritability
      was 90% (95% CI, 81%-95%) for myopia and 89% (95% CI, 81%-94%) for hyperopia. For
      total and corneal astigmatism, modeling showed dominant genetic effects are
      important; dominant genetic effects accounted for 47% to 49% of the variance of
      total astigmatism (95% CI, 37%-55%) and 42% to 61% of corneal astigmatism
      variance (95% CI, 8%-71%), with additive genetic factors accounting for 1% to 4%
      and 4% to 18%, respectively (95% CIs, 0%-13% and 0%-60%, respectively).
      CONCLUSIONS: Genetic effects are of major importance in myopia/hyperopia;
      astigmatism appears to be dominantly inherited.

PMID- 11328733
TI  - The relationship between ocular dimensions and refraction with adult stature: the
      Tanjong Pagar Survey.
AB  - PURPOSE: To describe the association of ocular dimensions and refraction with
      adult stature. METHODS: This was a population-based cross-sectional survey of
      adult Chinese aged 40 to 81 years residing in the Tanjong Pagar district in
      SINGAPORE: As part of the examination, ocular dimensions, including axial length,
      anterior chamber depth, lens thickness, and vitreous chamber depth, were measured
      using an A-mode ultrasound device. Corneal radius and refraction were determined
      with an autorefractor, with refraction further refined subjectively. Height (in
      meters) and weight (in kilograms) were measured using a standardized protocol,
      and body mass index (BMI) was calculated as weight divided by the square of the
      height (kilograms per square meter). RESULTS: Data on ocular biometry,
      refraction, height, and weight were available on 951 (55.4%) participants with
      phakic eyes. After controlling for age, sex, education, occupation, housing type,
      income, and weight, it was found that taller persons were more likely to have
      longer axial lengths (+0.23 mm longer axial length, for every 0.10 m difference
      in height), deeper anterior chambers (+0.07 mm), thinner lenses (-0.09 mm),
      longer vitreous chambers (+0.26 mm), and flatter corneas (+0.09 mm longer corneal
      radius), although refractions were similar. In contrast, heavier persons tended
      to have more hyperopic refractions (+0.22 D for every 10 kg difference in weight,
      +0.56 D for every 10 kg/m(2) difference in BMI) but similar ocular dimensions.
      CONCLUSIONS: Adult height is independently related to ocular dimensions, but does
      not appear to influence refraction. Thus, although taller persons are more likely
      to have longer globes, they also tend to have deeper anterior chambers, thinner
      lenses, and flatter corneas. Conversely, weight is independently related to
      refraction, although the exact biometric component responsible for this
      association is not apparent.

PMID- 11328734
TI  - In vitro model of infectious crystalline keratopathy: tissue architecture
      determines pattern of microbial spread.
AB  - PURPOSE: To develop an in vitro model of infectious crystalline keratopathy using
      human corneal buttons and to test the hypothesis that the compactness of the
      corneal stroma determines the pattern of microbial spread. METHODS: Twenty human
      corneal buttons obtained after penetrating keratoplasty for keratoconus (KC) and
      eight human corneal buttons obtained from eye bank (EB) donor eyes were
      maintained in organ culture. Fourteen buttons (10 KC and 4 EB donors) were
      maintained in a turgid state (swollen, edematous) and 14 in a nonturgid state
      (compact, normal state of deturgescence) by the omission or addition of 5%
      dextran to the culture medium. Eight KC and four EB nonturgid buttons and eight
      KC and four EB turgid buttons were inoculated with Streptococcus viridans
      (Lancefield group G, gram-positive) organisms. Two KC nonturgid and two KC turgid
      buttons were inoculated with Klebsiella oxytoca (gram-negative) organisms.
      Bacterial migration and spread in the tissue were observed by light and electron
      microscopy. RESULTS: Of the nonturgid buttons, six KC buttons and all four EB
      buttons inoculated with S. viridans and both KC buttons inoculated with K.
      oxytoca demonstrated an arborizing, crystallike pattern of bacterial spread. In
      the turgid buttons, five KC and all four EB buttons inoculated with S. viridans
      and both KC buttons inoculated with K. oxytoca demonstrated globular, amorphous
      colonies. This was in complete contrast to the needlelike branching appearance
      seen in nonturgid corneal buttons. Electron microscopy confirmed an interlamellar
      spread of the bacterial colonies. CONCLUSIONS: This is the first in vitro model
      of bacterial keratitis. It demonstrates that the pattern of spread of bacteria
      within corneal tissue is largely determined by the compactness of the corneal
      stroma. Altering tissue architecture changed the pattern of bacterial migration
      and spread. This model has considerable potential in further understanding host
      microbe interactions and microbial spread that occurs during infection.

PMID- 11328735
TI  - Stimulatory effect of pseudomonal elastase on collagen degradation by cultured
      keratocytes.
AB  - PURPOSE: The pathobiology of corneal ulceration induced by Pseudomonas aeruginosa
      was investigated by characterization of the pseudomonal pathogenic factors
      responsible for degradation of the collagen matrix. METHODS: Three-dimensional
      gels of type I collagen containing (or not) rabbit keratocytes were incubated in
      the presence of either culture supernatant of P. aeruginosa strain PAO1 or
      pseudomonal pathogenic factors (elastase, lipopolysaccharide, or exotoxin A), and
      the extent of collagen degradation was assessed after 24 hours by measurement of
      released hydroxyproline. Activation of matrix metalloproteinases (MMPs) produced
      by keratocytes was also examined by gelatin zymography and immunoblot analysis.
      RESULTS: In the absence of keratocytes, the PAO1-conditioned medium increased the
      extent of collagen degradation. The conditioned medium also promoted keratocyte
      mediated collagen degradation. Of the pseudomonal pathogenic factors examined,
      only elastase degraded collagen directly as well as stimulated keratocyte
      mediated collagen degradation. Culture supernatant of elastase-deficient P.
      aeruginosa (lasR or lasB) mutants had no effect on collagen degradation in the
      absence or presence of keratocytes. Elastase also induced the conversion of the
      inactive precursors of MMP-1, -2, -3, and -9 produced by keratocytes to the
      active forms of the enzymes. CONCLUSIONS: These results suggest that pseudomonal
      elastase both degrades type I collagen directly and promotes collagen degradation
      mediated by keratocytes, the latter effect being likely attributable, at least in
      part, to the activation of proMMPS:

PMID- 11328736
TI  - Doxil-induced chemomyectomy: effectiveness for permanent removal of orbicularis
      oculi muscle in monkey eyelid.
AB  - PURPOSE: To test the safety and effectiveness of Doxil chemomyectomy in monkey
      eyelids using treatment schedules and doses similar to those proposed for the
      human blepharospasm patients in Phase I and II trials. METHODS:
      Bupivacaine/hyaluronidase and Doxil were injected sequentially into the eyelids
      of five Cynomolgus monkeys. Eyelids received 1, 2, or 3 sets of injections. The
      monkeys were euthanatized at a minimum of 2 months and a maximum of 12 months
      after the final treatment. The eyelids were prepared for histologic examination,
      and muscle fiber loss was quantified. RESULTS: All Doxil injections resulted in a
      significant loss of myofibers. No bruising, ulceration, or other skin injuries
      occurred, even after a third injection regimen within a single treated eyelid.
      Two-day preinjury with a bupivacaine/hyaluronidase mixture had a significant
      adjuvant effect. CONCLUSIONS: Doxil chemomyectomy is an effective protocol to
      permanently remove muscle from injected eyelids in nonhuman primates. Serial
      injections over the course of several months using the preinjury protocol
      combined with Doxil treatment significantly increased Doxil's myotoxic effects.
      Additionally, the injection of the liposome-encapsulated form of doxorubicin did
      not result in skin injury or ulceration. Species differences demonstrated the
      importance of testing these drugs in nonhuman primates. Thus, repeated doses of
      Doxil may prove to be as clinically effective as free doxorubicin injections in
      reducing muscle spasms in blepharospasm patients but with increased safety to the
      skin and tissue around the injection site.

PMID- 11328737
TI  - Retinal morphology and ERG response in the DBA/2NNia mouse model of angle-closure
      glaucoma.
AB  - PURPOSE: To document the time course of retinal dysfunction by scotopic
      electroretinography (ERG) and by quantitative morphology in eyes of the DBA/2NNia
      substrain of mouse (DBA) with inherited angle-closure glaucoma. METHODS: DBA and
      control C57BL/6J (C57) mice were studied by ERG recordings from 5 to 15 months of
      age, and by morphology from 1 to 14 months of age. Scotopic ERGs were
      simultaneously recorded from both eyes of dark-adapted anesthetized mice. Changes
      in the central neuronal retina were evaluated by quantitative morphometry
      performed on serial semithin sections of Epon-embedded eyes. RESULTS: When
      compared with normal C57 mice, DBA mice showed significant reductions of the a
      wave and b-wave amplitudes by 7 to 8 months, and the decline continued as the
      animals aged. The b-wave implicit time in DBA mice showed a gradual prolongation
      beginning at 8 months of age, when compared with C57 mice. Logistic regression
      analyses revealed significant correlations in a- and b-wave amplitude reductions
      between ipsilateral and contralateral eyes of DBA mice at ages when ERG
      parameters were greatly altered. Morphologically, thinning of the whole retina
      was already evident in DBA mice at 4 months of age, but loss of ganglion cells
      and thinning of the outer plexiform layer were first seen in 7- to 8-month-old
      animals. These changes progressed to the end of the 13-month period studied.
      CONCLUSIONS: Progressive thinning of the outer retinal layers in DBA mice was
      found to correlate with decreases in ERG a- and b-wave amplitudes, both occurring
      from the age of 7 to 8 months onward. Similarities with the findings in human
      late-stage glaucomatous retinopathy indicate the relevance of this animal model
      in further glaucoma research.

PMID- 11328738
TI  - The s-cone PHNR and pattern ERG in primary open angle glaucoma.
AB  - PURPOSE: To compare the sensitivity of the photopic negative response (PhNR) from
      the shortwave (S)-sensitive and the long (L)- and medium (M)-wave-sensitive cone
      electroretinograms (ERGs), with the pattern electroretinogram (PERG) in the early
      stages of primary open-angle glaucoma (POAG). METHODS: Eighteen patients under
      treatment for diagnosed POAG and 19 normal control subjects were investigated. S
      cone ERGs were elicited using adaptation to 650-nm light to suppress L-cone
      activity, and substitution between 450 nm and 535 nm to silence M-cone response
      at luminances higher than rod saturation. PhNRs from the L&M-cone pathways were
      elicited by a 200-msec pulse of red light (650 nm) on a continuous blue (450 nm)
      background. PERGs were recorded in accordance with the International Society for
      Clinical Electrophysiology of Vision (ISCEV) standard. RESULTS: Each method
      showed a statistically significant difference in the two groups. The S-cone PhNR
      was the most sensitive test and provided the most statistically significant
      results, with the largest area enclosed by the receiver operating characteristic
      (ROC) curve. CONCLUSIONS: The findings indicate that all three types of ERG may
      be useful in glaucoma investigation. The L- and M-cone PhNRs may have a role in
      monitoring established glaucoma. The previously reported high sensitivity of the
      PERG was confirmed. Extensive diffuse damage to S-cone bipolar and bistratified
      ganglion cells appears to occur at a very early stage in POAG, owing to a
      pressure-related mechanism, and the S-cone PhNR was the most sensitive test. It
      may in future have an important role in diagnosis and monitoring of early
      glaucoma. Further investigation of this possibility is recommended.

PMID- 11328739
TI  - Serum autoantibody against glutathione S-transferase in patients with glaucoma.
AB  - PURPOSE: To identify retinal proteins that are the targets of serum
      autoantibodies in patients with glaucoma. METHODS: To identify retinal antigens
      that are recognized by the sera of patients with glaucoma, immunoreactive bands
      were separated, by using two-dimensional gel electrophoresis of the bovine
      retinal soluble fraction. A 29-kDa band was then selected for further analysis.
      Tryptic peptides of the 29-kDa band were analyzed using electrospray mass
      spectrometry to identify the protein. After protein identification,
      immunoreactivity against this newly identified protein was studied by Western
      blot analysis using sera from 65 patients with glaucoma (25 with primary open
      angle glaucoma [POAG]; 40 with normal-pressure glaucoma [NPG]) and 25 age-matched
      healthy subjects. In addition, serum antibody titers were compared in these
      groups, by using a specific enzyme-linked immunosorbent assay (ELISA). RESULTS:
      The 29-kDa band was identified as glutathione S-transferase (GST). Western blot
      analysis revealed that serum antibodies against GST antigen were recognized in 34
      (52%) of 65 patients with glaucoma (22 of NPG and 12 of POAG) and 5 (20%) of 25
      age-matched control subjects (chi(2) test, P < 0.05). By ELISA, it was also found
      that patients with glaucoma had higher titers of anti-GST antibody, compared with
      the control group (Mann-Whitney test; NPG versus control, P = 0.013; POAG versus
      control, P = 0.0006). CONCLUSIONS: These findings indicate that GST is one of the
      retinal antigens targeted by the serum antibodies detected in some patients with
      glaucoma.

PMID- 11328740
TI  - Effect of aminoguanidine, a nitric oxide synthase inhibitor, on ocular infection
      with herpes simplex virus in Balb/c mice.
AB  - PURPOSE: To study the effect of aminoguanidine (AMG), an inhibitor of nitric
      oxide production, on the ocular infection of Balb/c mice with herpes simplex
      virus (HSV) type 1 strain F and HSV-2 strain G. METHODS: Animals were treated
      with different amounts of AMG (0.5, 0.1, and 0.05 mg/mouse) by topical
      application in the eye from postinfection (PI) days -2 through +5, considering 0
      the day of infection. At different PI days, development of herpetic keratitis was
      evaluated in treated and control mice. RESULTS: Treated animals showed a dose
      dependent increase in ocular disease after viral infection, compared with control
      animals. Viral titers in ocular washings were higher in AMG-treated mice (PI day
      2, HSV-1: AMG 0.5 mg, 1.3 x 10(3) plaque-forming units (PFU)/ml; control, 0. 22 x
      10(2) PFU/ml, P < 0.025). At PI day 3, control corneas had only scattered
      inflammatory cells, whereas those from treated animals showed a conspicuous
      infiltrate consisting primarily of neutrophils. Viral titers were also higher in
      brains of treated mice. These animals died earlier and in a greater proportion
      than control animals (percentage of mortality, PI day 12, HSV-1: AMG 0.5 mg, 40%
      +/- 4%; control, 18% +/- 3%, P < 0.05). CONCLUSIONS: These data indicate an
      inhibitory effect of nitric oxide on HSV ocular infection.

PMID- 11328741
TI  - CD69 expression on peripheral CD4+ T cells parallels disease activity and is
      reduced by mycophenolate mofetil therapy in uveitis.
AB  - PURPOSE: To assess the effects of mycophenolate mofetil (MMF) therapy on T helper
      cell activation status, using CD69 expression and cytokine profile with flow
      cytometry in relation to clinical activity in uveitis. METHODS: Patients with
      posterior or intermediate uveitis treated with MMF (n = 10), patients with active
      uveitis not treated with MMF and receiving no or minimal therapy (n = 10), and
      healthy volunteers (n = 21) had peripheral blood lymphocyte immunofluorescence
      analysis for T helper cell (CD4, CD3) markers, activation status (CD69), and
      intracellular cytokine (interleukin [IL]-2, interferon [IFN]-gamma, and IL-4)
      levels. Patients were compared before and during MMF therapy in relation to T
      helper cell activation and clinical activity. RESULTS: Patients with active
      uveitis not treated with MMF and receiving no or minimal therapy had increased
      frequency of CD69-positive CD4 T cells (10.5% +/- 4.6%, P = 0.0007) compared with
      healthy volunteers (3.3% +/- 2.7%). Of all patients receiving MMF therapy, only
      patients with moderate to severe uveitis activity in the pre-MMF treatment group
      (n = 5; 15.5% +/- 5.0%, P = 0.004) had increased frequency of CD69-positive CD4 T
      cells compared with healthy volunteers. During MMF therapy, a significant
      reduction in frequency of CD69-positive CD4 T cells occurred in patients with
      prior moderate to severe uveitis activity (to 8.9% +/- 3.8%, P = 0.04). Levels of
      CD69-positive CD4 T cells in patients who had had inactive or mildly active
      disease (n = 5) before and during MMF therapy were comparable with levels in
      healthy volunteers. No significant changes in cytokine levels were found between
      the patient and control groups. A significant association between changes in
      frequency of CD69-positive CD4 T cells and changes in visual acuity (P = 0.008)
      and changes in vitreal haze (binocular indirect ophthalmoscopy score; P = 0.01)
      was observed in MMF-treated patients with prior moderate to severe uveitis
      activity. CONCLUSIONS: Reduction in uveitis activity during MMF therapy
      correlates with reduction in frequency of peripheral blood CD69-positive CD4
      cells. The frequency of CD69-positive CD4 T cells is a measure of activity in
      posterior uveitis and may guide adequate immunosuppression.

PMID- 11328742
TI  - The critical role of lymph nodes in corneal alloimmunization and graft rejection.
AB  - PURPOSE: To elucidate the role of draining cervical lymph nodes (CLNs) in corneal
      alloimmunity. METHODS: Fully mismatched orthotopic corneal transplantation was
      performed in BALB/c hosts that had their CLNs excised before transplantation
      (CLN(-)). Normal hosts (CLN(+)), splenectomized mice (Sp(-)), and those without
      either CLNs or spleen (CLN(-)/Sp(-)) served as comparison groups. To determine
      the contribution of CLNs to alloimmunity more directly, CLN(-) mice were
      reconstituted by grafting LNs from other BALB/c mice to their cervical lymphatic
      chains, thus deriving CLN(-/+) mice. Tetramethyl rhodamine isothiocyanate's
      (TRITC) flow to draining CLNs was used as a measure of afferent lymph flow. Graft
      survival and allospecific delayed-type hypersensitivity (DTH) were used as
      measures of alloreactivity. RESULTS: Fifty percent of normal control and 12% of
      Sp(-) hosts accepted the allografts. In contrast, 100% of CLN(-) and 88% of CLN(
      )/Sp(-) hosts accepted allografts indefinitely (P < 0.01). Additionally, all CLN(
      ) hosts failed to demonstrate allospecific DTH (P < 0.001). CLN(-/+) mice
      reconstituted with LN from naive animals showed graft survival rates and DTH
      responses that were indistinguishable from those of naive CLN(+) mice. Of
      particular interest, however, is that mice reconstituted with CLNs from hosts
      with rejected corneal grafts had swift rejection of subsequent corneal grafts and
      exhibited strong donor-specific DTH. In contrast, mice reconstituted with CLNs
      from hosts with accepted corneal grafts showed rejection of subsequent corneal
      grafts in a manner that was indistinguishable from rejection in naive CLN(+)
      hosts. CONCLUSIONS: Draining CLNs play a critical role in allosensitization and
      rejection. In contrast to the spleen, draining CLNs do not appear to play a
      critical role in tolerance induction in corneal transplantation.

PMID- 11328743
TI  - Argpyrimidine, a blue fluorophore in human lens proteins: high levels in
      brunescent cataractous lenses.
AB  - PURPOSE: To determine whether the human lens contains argpyrimidine, a
      modification of arginine by methylglyoxal, to establish how argpyrimidine content
      relates to lens aging and cataract formation. METHODS: A monoclonal antibody was
      used to measure argpyrimidine by a competitive ELISA in water soluble (WS) and
      insoluble (WI) lens fractions from young, aged, nuclear cataractous, and
      brunescent cataractous lenses. Brunescent cataractous lens proteins were digested
      by enzymes, the digest was subjected to HPLC, and the eluate was analyzed for
      argpyrimidine. Lens proteins from aged lenses (from donors 65 to 80 years of age)
      were fractionated on a Sephadex G-200 column, and the crystallins were tested for
      argpyrimidine. RESULTS: The competitive ELISA showed two to three times as much
      argpyrimidine in water-insoluble proteins as in water-soluble proteins. Although
      no clear cut increase with the age of the lens donors in either the water-soluble
      or the insoluble protein fractions was found, the argpyrimidine levels in
      brunescent cataractous lenses were significantly higher (254.0 +/- 155 pmol/mg
      protein, P < 0.005) than in age-matched, aged (16.1 +/- 8 pmol/mg) or nuclear
      cataractous lenses (49.0 +/- 26 pmol/mg). Lenses from diabetic individuals showed
      a modest increase (50.3 pmol/mg) compared with age-matched normal lenses. HPLC
      results provided additional evidence that human lenses contain argpyrimidine.
      Western blotting experiments showed consistently stronger reactions with
      cataractous lens proteins than those from noncataractous lenses, and
      argpyrimidine was found in both crystallin monomers and polymers. All crystallins
      and several cross-linked high-molecular-weight aggregates reacted with the
      antibody to argpyrimidine, but a protein of approximately 28 kDa in the alpha
      crystallin fraction displayed the greatest immunoreactivity. CONCLUSIONS:
      Methylglyoxal modifies arginine within the human lens, and the changes occur at a
      much higher rate in brunescent lens proteins than in either nuclear cataractous
      or normal lenses. All crystallins contained argpyrimidine and covalently cross
      linked aggregates. This is the first report of immunologic evidence for an
      arginine modification in the human lens by a physiologically important alpha
      dicarbonyl compound.

PMID- 11328744
TI  - FGF: an autocrine regulator of human lens cell growth independent of added
      stimuli.
AB  - PURPOSE: Posterior capsule opacification (PCO) arises because of a persistent
      growth of lens epithelial cells. Cultured human lens cells residing on their
      native collagen capsule and maintained in serum-free medium actively grow and
      thus show an intrinsic capacity for regulation. In the present study, the authors
      investigated the role of the putative FGF autocrine system in human capsular
      bags. METHODS: Capsular bags were prepared from human donor eyes and maintained
      in a 5% CO(2) atmosphere at 35 degrees C. On-going observations were by phase
      contrast microscopy. Cellular architecture was examined by fluorescence
      cytochemistry. De novo protein synthesis was determined by the incorporation of
      35S-methionine. Basic fibroblast growth factor (FGF) and FGF receptor (R)-1 were
      detected using enzyme-linked immunosorbent assay (ELISA) and reverse
      transcription-polymerase chain reaction (RT-PCR) techniques. FGFR-1 inhibition
      was achieved using the specific antagonist SU5402. RESULTS: Human lens epithelial
      cells can maintain metabolic activity for more than 1 year in a protein-free
      medium. Basic FGF was shown to be present in capsular bags throughout culture and
      also in capsular bags removed from donor eyes that had previously undergone
      cataract surgery. Furthermore, FGFR-1 was identified. Inhibition of FGFR-1 caused
      a significant retardation of growth on the posterior capsule. On no occasion did
      any treated bag reach confluence, whereas all match-paired control samples did.
      CONCLUSIONS: The results provide evidence that FGF plays an integral role in the
      long-term survival and growth of human lens epithelial cells, independent of
      external stimuli. Inhibition of FGFR-1 by specific synthetic molecules, such as
      SU5402, could provide a potential therapeutic approach to resolving PCO.

PMID- 11328745
TI  - Systematic immunolocalization of retinoid receptors in developing and adult mouse
      eyes.
AB  - PURPOSE: To determine the localization of retinoic acid receptors (RAR) alpha,
      beta, and gamma and retinoid X receptors (RXR) alpha, beta, and gamma in
      developing and adult mouse eyes at the level of single cells. METHODS:
      Immunohistochemistry was performed on paraformaldehyde-lysine-periodate-fixed
      cryosections of mouse eyes, from embryonic day 10.5 to adulthood, with polyclonal
      antibodies directed against each receptor isoform. Histologic sections from null
      mutant mice for each receptor served as negative controls. RESULTS: RARalpha was
      present ubiquitously in the prenatal eye and preferentially located in the
      posnatal retina and ciliary body. RARbeta was detected predominantly in the
      periocular mesenchyme and ciliary body. RARgamma was distributed in the
      periocular mesenchyme, choroid, sclera, cornea, conjunctiva, and lids. RXRalpha
      was found preferentially in the prenatal periocular mesenchyme and retina and in
      the postnatal ciliary body, cornea, and conjunctiva. RXRbeta was ubiquitous at
      all the stages. RXRgamma was detected mainly in subsets of prenatal retinal cells
      and in postnatal ganglion cells as well as a subset of photoreceptor cells that
      were characterized as cones in adults. CONCLUSIONS: RARalpha, beta, and gamma and
      RXRalpha and gamma exhibit specific and dynamic patterns of distribution in
      ocular tissues throughout the course of development. The abundance of RARbeta,
      RARgamma, and RXRalpha in the periocular mesenchyme suggests that this tissue
      represents an important site of retinoid actions during eye development and in
      adulthood.

PMID- 11328747
TI  - Facilitation of artificial retinal detachment for macular translocation surgery
      tested in rabbit.
AB  - PURPOSE: For macular translocation surgery, the native attached retina has to be
      detached either locally or completely. Although different surgical techniques are
      used, there is a general search for supporting procedures that facilitate and
      accelerate the retinal detachment. METHODS: Pars plana vitrectomies were
      performed in pigmented rabbits. In all experimental groups, a local retinal
      detachment was created by infusing the test solution with a thin glass
      micropipette attached to a glass syringe. In control animals a standard balanced
      salt solution was used at room temperature, in combination with a standard
      vitrectomy light source. In two test groups, a calcium- and magnesium-free
      solution was used for the vitrectomy, under illumination by a standard light
      source in group I (solution at room temperature) and group II (solution heated up
      to body temperature). In group III the rabbits were dark-adapted for half an
      hour, and then, during surgery, a red filter was used in front of the light
      source (standard balanced salt solution at room temperature). After the rabbits
      were killed at the end of surgery, the adherence of the retinal pigment
      epithelium (RPE) to the neural retina in the detachment area was quantified
      microscopically, and the morphologic integrity of the detached retinal tissue was
      examined by light and electron microscopy. No electrophysiology was performed.
      RESULTS: In all four groups, it was possible to detach the retina. The maximum
      adherence of the RPE cells to the neural retina was observed in the control
      group. Virtually no decrease in adherence was found in test group II (36 degrees
      C solution without calcium and magnesium), whereas a significant decrease was
      seen in both group I (calcium- and magnesium-free solution at room temperature)
      and group III (dark adaptation-red light technique; standard balanced salt
      solution at room temperature). In none of the experimental groups was any obvious
      damage of the retinal structure observed, even after exposure to the test
      solutions for 60 minutes. CONCLUSIONS: Both dark adaptation (red illumination)
      and the use of a calcium chloride- and magnesium chloride-free solution (at room
      temperature) can facilitate retinal detachment in macular translocation surgery.
      Both techniques are proposed as a gentle support for the operation, because they
      protect an intact RPE cell layer and do not cause retinal damage at the
      ultrastructural level.

PMID- 11328746
TI  - Autosomal dominant retinal degeneration and bone loss in patients with a 12-bp
      deletion in the CRX gene.
AB  - PURPOSE: To define the phenotypic expression of a deletion in the gene encoding
      the transcription factor CRX in a large, seven-generation, white family. METHODS:
      Fourteen affected individuals, all heterozygous for the Leu146del12 mutation in
      the cone-rod homeobox gene (CRX), and four nonaffected relatives from the same
      family were examined with visual function tests, and 10 underwent bone mineral
      density (BMD) measurement. RESULTS: The ability of the mutated CRX protein to
      transactivate rhodopsin promoter was decreased by approximately 25%, and its
      ability to react synergistically with neural retinal leucine zipper (NRL) was
      reduced by more than 30%. The affected members of the family had an autosomal
      dominant ocular condition most closely resembling Leber congenital amaurosis
      (LCA) with severe visual impairment at an early age. Depending on age, affected
      members showed varying degrees of significant visual acuity loss, elevated dark
      adaptation thresholds, significantly reduced cone and rod electroretinogram (ERG)
      amplitudes, and progressive constriction of the visual fields, in most cases
      leading to complete blindness. Six affected members had reduced levels of BMD in
      the spine and the hip (osteopenia). Four affected female members who were
      receiving long-term hormonal replacement therapy (HRT) demonstrated normal values
      of BMD. CONCLUSIONS: This large deletion of the CRX gene is associated with a
      severe form of autosomal dominant retinal degeneration. Affected members not
      receiving HRT showed reduced BMD (osteopenia). This phenotype may reflect the
      abnormal influence of mutant CRX on both retinal and pineal development.

PMID- 11328748
TI  - Macular pigment optical density before and after cataract extraction.
AB  - PURPOSE: Psychophysical methods of measuring macular pigment (MP) use comparisons
      of short- and midwave light in the fovea and parafovea to derive optical density
      estimates. This light must pass through the crystalline lens before absorption by
      the MPs can occur. The effect of lens absorption on these measures has not been
      adequately determined. The present study assesses the influence of lens
      absorption on MP measurements by comparing MP optical density (MPOD) measured
      before and after cataract extraction. METHODS: MPOD was measured using flicker
      photometry in free view at 458 nm with a 1 degrees stimulus. Twenty-nine eyes
      from 24 patients with cataracts sufficiently severe to require cataract
      extraction were evaluated. RESULTS: In the entire group of 24 patients, the mean
      (+/-SD) age measured 68.7 +/- 9.5 years, and the mean MPOD measured 0.19 +/-
      0.11. For all 29 eyes measured, MPOD averaged 0.206 +/- 0.13 before and 0.18 +/-
      0.12 after cataract extraction. MPOD measurements at the two time points (mean
      8.1 +/- 4.7 weeks after surgery) were highly correlated (r = +0.58), suggesting
      that a cataractous lens does not influence the MP measurement technique.
      CONCLUSIONS: Psychophysical techniques can be used to obtain reliable
      measurements of MP in elderly subjects, even in those with cataracts. Moreover,
      differences in retinal illuminance due to varying opaqueness of the crystalline
      lens do not seem to have a measurable influence on MPOD.

PMID- 11328749
TI  - Multifocal ERG findings in complete type congenital stationary night blindness.
AB  - PURPOSE: To study the multifocal electroretinogram (mfERG) in patients with the
      complete type of congenital stationary night blindness (cCSNB), which is thought
      to be due to a defect in neurotransmission from the photoreceptors to the ON
      bipolar cells. METHODS: mfERGs were recorded with the VERIS recording system from
      four patients with cCSNB, none of whom had nystagmus. The stimulus array
      consisted of 61 hexagons, and the total recording time was approximately 4
      minutes. The amplitudes and implicit times of the first- and second-order kernels
      of the local responses were compared with those from 20 myopic controls.
      Waveforms of the summed response from all locations were also compared between
      the two groups. RESULTS: The first-order kernels of the mfERGs of cCSNB patients
      had normal amplitudes but delayed implicit times for nearly the whole field
      tested. The second-order kernel was severely attenuated in amplitude in cCSNB
      patients. The ratios of the second- to first-order kernel amplitudes were
      significantly reduced in cCSNB and clearly separated the cCSNB group from the
      control group without any overlap of the values. CONCLUSIONS: The second-order
      kernel, which is involved in adaptative mechanism of the retina to repeated
      flashes, is selectively reduced in cCSNB. The delay of the implicit times of the
      first-order kernel in patients with cCSNB may be related to the severe amplitude
      reduction of the second-order kernel.

PMID- 11328750
TI  - Inhibition of TNF-alpha-induced sickle RBC retention in retina by a VLA-4
      antagonist.
AB  - PURPOSE: Patients with sickle cell disease have elevated circulating levels of
      cytokines including tumor necrosis factor (TNF) alpha. TNF-alpha stimulates
      expression by endothelial cells of adhesion molecules, including vascular cell
      adhesion molecule (VCAM) 1. Others have demonstrated that VLA-4
      (alpha(4)beta(1)), a ligand for VCAM-1 or fibronectin, is present on a fraction
      of sickle reticulocytes. The intent of this study was to determine, using a rat
      model, if TNF-alpha increases retention of sickle erythrocytes in retina and if
      that retention can be inhibited. METHODS: TNF-alpha was given intraperitoneally
      to rats 5 hours before IV administration of FITC-labeled, density-separated
      sickle erythrocytes. After 5 minutes, rats were exsanguinated, and retinas were
      excised and incubated for ADPase activity, permitting the determination of the
      number and location of retained cells. RESULTS: TNF-alpha caused a three- to
      fourfold increase in retention of sickle erythrocytes in retinal capillaries (P <
      0.05) but not of normal human erythrocytes. Preincubation of sickle erythrocytes
      with TBC772, a peptide that blocks the binding of alpha(4)beta(1) and
      alpha(4)beta(7), or a monoclonal antibody against VLA-4 (19H8), significantly
      inhibited the TNF-alpha-induced retention (P < or = 0.02), whereas a control
      cyclic peptide and antibody had no effect. IV TBC772 also inhibited sickle
      erythrocyte retention (P = 0.01). Two intravenously administered anti-fibronectin
      antibodies inhibited sickle cell retention as well, but an anti-rat VCAM-1
      antibody did not inhibit retention. CONCLUSIONS: The authors conclude that TNF
      alpha stimulates retention of sickle erythrocytes in the retinal vasculature.
      This increased retention can be blocked by a VLA-4 antagonist, suggesting that
      the cells retained after cytokine stimulation are reticulocytes. The counter
      receptor for VLA-4 in this rat retina model appears to be fibronectin and not
      VCAM-1, based on data obtained using antibodies against these molecules.

PMID- 11328751
TI  - Blue light-induced apoptosis of A2E-containing RPE: involvement of caspase-3 and
      protection by Bcl-2.
AB  - PURPOSE: The lipofuscin fluorophore A2E has been shown to mediate blue light
      induced damage to retinal pigment epithelial (RPE) cells. The purpose of this
      study was to evaluate caspase-3 and Bcl-2 as executor and modulator,
      respectively, of the cell death program that is initiated in A2E-containing cells
      in response to blue light. METHODS: Human RPE cells (ARPE-19) that had
      accumulated A2E were exposed to blue light. Caspase-3 activity was assayed by
      observing cleavage of a fluorogenic peptide substrate, and the effect of a
      peptide inhibitor of caspase-3 (Z-DEVD-fmk) on the quantity of apoptotic nuclei
      was determined. ARPE-19 cells were transfected with either a neomycin-selectable
      expression vector containing Bcl-2 cDNA or a control neomycin-selectable
      expression vector without Bcl-2 cDNA. Expression of Bcl-2 transcripts by
      independently derived clones was established by in situ hybridization, and Bcl-2
      protein expression was confirmed by Western blot analysis. Cell viability was
      assayed by TdT-dUTP terminal nick-end labeling (TUNEL) in conjunction with 4'6'
      diamidino-2-phenylindole (DAPI) staining and by fluorescence staining of the
      nuclei of membrane-compromised cells. RESULTS: In RPE cells that had previously
      accumulated A2E, caspase-3 activity was detected within 5 hours of blue light
      exposure. The incidence of apoptotic nuclei was attenuated when A2E-containing
      RPE cells were exposed to blue light in the presence of caspase-3 inhibitor and
      in A2E-loaded RPE cells that had been stably transfected with Bcl-2. CONCLUSIONS:
      Blue light illumination of RPE in the setting of intracellular A2E initiates a
      cell death program that is executed by a proteolytic caspase cascade and that is
      regulated by Bcl-2.

PMID- 11328752
TI  - FGFR1, signaling, and AP-1 expression after retinal detachment: reactive Muller
      and RPE cells.
AB  - PURPOSE: To identify changes in cellular signaling pathways and AP-1 expression
      in retina and retinal pigmented epithelium (RPE) after experimental retinal
      detachment (RD). METHODS: Cat and rabbit neural retinas were separated from the
      RPE in vivo for 5 minutes to 28 days. Tissues were removed and processed for
      Western blotting, immunohistochemistry, in situ hybridization, and
      immunoprecipitation experiments. RESULTS: An ordered sequence of events occurs
      after RD: (1) fibroblast growth factor (FGF) receptor 1 (FGFR1, flg) is
      phosphorylated in the retina within 15 minutes and dephosphorylated 2 hours after
      RD; (2) The extracellular signal-regulated kinase (ERK) is phosphorylated in both
      Muller and RPE cells within 15 minutes and remains so for several days; (3) De
      novo expression of c-fos mRNA coincides with increased c-Fos and c-Jun
      immunoreactivity in both Muller and RPE cells; (4) CREB is phosphorylated in a
      subpopulation of photoreceptors; and (5) STAT3 and NF-kappaB are activated in
      inner nuclear layer cells by 1 day of RD. CONCLUSIONS: These data suggest that
      nonneuronal cells (RPE and Muller cells) respond to RD very rapidly by
      stimulating ERK signaling and AP-1 transcription factor expression. Furthermore,
      these data suggest that basic fibroblast growth factor (FGF-2, bFGF) is involved
      in initiating the retina's earliest responses to RD. The events described here
      precede changes in gene expression and morphology that can have serious effects
      on visual outcome in humans treated for retinal detachment or other retinal
      injuries.

PMID- 11328753
TI  - Oxidative stress induces heme oxygenase-1 immunoreactivity in Muller cells of
      mouse retina in organ culture.
AB  - PURPOSE: Heme oxygenase (HO)-1 immunoreactivity (IR) was examined in normal
      untreated retina and in retinal explants after in vitro treatment with stress
      agents. METHODS: Enucleated eyes from young adult C3H mice were immediately fixed
      and cryosectioned and the retina sections processed for immunocytochemistry with
      antibodies against HO-1 and glial fibrillary acidic protein (GFAP). From other
      eyes retinas were isolated and maintained in organ culture, either untreated for
      4 days maximum or for 21 hours during which the explants were treated the first 3
      hours with selected doses of sodium arsenate or hydrogen peroxide. Thereafter,
      the explants were processed identically with the normal tissue. RESULTS: In the
      normal retina, HO-1 and GFAP IR was very low. The culturing itself resulted in an
      increase in both HO-1 and GFAP immunolabeling in Muller cells of explanted
      retinas. Both sodium arsenate and hydrogen peroxide further induced strong HO-1
      IR in Muller cells but not in other retinal cells. In contrast to HO-1, GFAP
      staining in Muller cells was not altered as a result of treatment, either by
      sodium arsenate or hydrogen peroxide at any concentration used. CONCLUSIONS: The
      results show for the first time that HO-1 can be induced in the retina in vitro
      by conditions of oxidative stress and that enzyme expression is confined
      exclusively to Muller cells.

PMID- 11328755
TI  - L- and M-cone-driven electroretinograms in Stargardt's macular dystrophy-fundus
      flavimaculatus.
AB  - PURPOSE: To study the dynamics of the long (L)- and middle (M)-wavelength
      sensitive cone-driven pathways and their interactions in patients with
      Stargardt's macular dystrophy-fundus flavimaculatus (SMD-FF) and to correlate
      them with other clinical parameters and individual genotypes. METHODS: Forty
      seven patients with SMD-FF participated in the study. In addition to standard 30
      Hz flicker electroretinograms (30-Hz fERG), ERG responses were measured to
      stimuli that modulated exclusively the L or the M cones (L/M cones) or the two
      simultaneously. Blood samples were screened for mutations in the 50 exons of the
      ABCA4 gene. RESULTS: Patients with SMD-FF did not show a decrease in the mean L/M
      cone-driven ERG sensitivity, but there was a significant increase in the
      interindividual variability. The mean L-/M-cone weighting ratio was normal.
      However, the L-cone-driven ERG was significantly phase delayed, whereas the M
      cone-driven ERG was significantly phase advanced. These phase changes were
      significantly correlated with disease duration. The amplitude and implicit time
      of the standard 30-Hz fERG both correlated significantly with the L/M-cone-driven
      ERG sensitivity and with the phase difference between the L/M-cone-driven ERGs,
      indicating the complex origin of the standard 30-Hz fERG. Probable disease
      associated mutations in the ABCA4 gene were found in 40 of 45 patients,
      suggesting that they form a genetically fairly uniform SMD-FF study group. There
      was no correlation between the genotype and the L/M-cone-driven ERGS:
      CONCLUSIONS: The changes in L/M-cone-driven ERG sensitivity and phase possibly
      represent two independent disease processes. The phase changes are similar to
      those found in patients with retinitis pigmentosa and possibly are a general
      feature of retinal dystrophies.

PMID- 11328754
TI  - Systemic administration of phenyl-N-tert-butylnitrone protects the retina from
      light damage.
AB  - PURPOSE: This study was conducted to test the hypothesis that phenyl-N-tert
      butylnitrone (PBN), a spin-trapping agent known to cross the blood-brain barrier
      and protect the brain from ischemia-reperfusion injury, is incorporated into the
      retina after intraperitoneal injection and protects photoreceptor cells from the
      damaging effects of constant visible light. METHODS: Albino rats were injected
      intraperitoneally with PBN (aqueous solution) or water, or were not injected, and
      then were placed in constant light (2700 lux) for 24 hours. The incorporation of
      PBN into the retina was determined by high-performance liquid chromatography.
      Electroretinograms (ERGs) were recorded before light treatment and 1 and 15 days
      after the cessation of exposure to constant light. Eyes were taken for histology
      at each time point and outer nuclear layer (ONL) thickness determined. RESULTS:
      PBN was incorporated into the retina after intraperitoneal injection. Both
      control (water-injected and uninjected) groups exposed to constant light
      maintained only 28% of ONL thickness and 20% of retinal function, compared with
      the unexposed control group. In contrast, the PBN-treated animals maintained 80%
      of ONL thickness and exhibited 87% of retinal function. CONCLUSIONS: PBN protects
      the albino rat retina from the damaging effects of constant light stress. That
      light-induced and hereditary retinal degenerations share certain morphologic
      hallmarks and follow a similar apoptotic mechanism of degeneration raises the
      possibility of pharmacologic therapy for hereditary and environmentally induced
      neurodegenerative disorders.

PMID- 11328756
TI  - Age-related changes in monochromatic wave aberrations of the human eye.
AB  - PURPOSE: To investigate the relations between age and the optical aberrations of
      the whole eye. The eye's optical quality, as measured by the modulation transfer
      function (MTF), degrades with age, but the MTF does not provide a means to assess
      the contributions of individual aberrations, such as coma, spherical aberration,
      and other higher order aberrations to changes in optical quality. The method used
      in this study provides measures of individual aberrations and overall optical
      quality. METHODS: Wave aberrations in 38 subjects were measured psychophysically
      using a spatially resolved refractometer. Data were fit with Zernike polynomials
      up to the seventh order to provide estimates of 35 individual aberration terms.
      MTFs and root mean square (RMS) wavefront errors were calculated. Subjects ranged
      in age from 22.9 to 64.5 years, with spherical equivalent corrections ranging
      from +0.5 to -6.0 D. RESULTS: Overall RMS wavefront error (excluding tilts,
      astigmatism, and defocus) was significantly positively correlated with age (r =
      0.33, P = 0.042). RMS error for the highest order aberrations measured (fifth
      through seventh order) showed a strong positive correlation with age (r = 0.57, P
      = 0.0002). Image quality, as quantified by the MTF, also degraded with age.
      CONCLUSIONS: Wave aberrations of the eye increase with age. This increase is
      consistent with the loss of contrast sensitivity with age observed by other
      investigators.

PMID- 11328757
TI  - Ocular aberrations before and after myopic corneal refractive surgery: LASIK
      induced changes measured with laser ray tracing.
AB  - PURPOSE: To determine objectively the changes in the ocular aberrations (3rd
      order and above) induced by myopic LASIK refractive surgery and its impact on
      image quality. METHODS: The ocular aberrations of 22 normal myopic eyes
      (preoperative refraction ranged from -13 to -2 D) were measured before (2.9 +/-
      4.3 weeks) and after (7.7 +/- 3.2 weeks) LASIK refractive surgery using a laser
      ray tracing technique. A set of laser pencils is sequentially delivered onto the
      eye through different pupil locations. For each ray, the corresponding retinal
      image is collected on a CCD camera. The displacement of the image centroid with
      respect to a reference provides direct information of the ocular aberrations.
      Root-mean-square (RMS) wavefront error was taken as image quality metric.
      RESULTS: RMS wavefront error increased significantly in all eyes but two after
      surgery. On average, LASIK induced a significant (P = 0.0003) 1.9-fold increase
      in the RMS error for a 6.5-mm pupil. The main contribution was due to the
      increase (fourfold, P < 0.0001) of spherical aberration. The increase in the RMS
      for a 3-mm pupil (1.7-fold) was also significant (P = 0.02). The modulation
      transfer (computed for 6.5-mm pupil) decreased on average by a factor of 2 for
      middle-high spatial frequencies. CONCLUSIONS: (1) Laser ray tracing is a well
      suited, robust, and reliable technique for the evaluation of the change of ocular
      aberrations with refractive surgery. (2) Refractive surgery induces important
      amounts of 3rd and higher order aberrations. The largest increase occurs for
      spherical aberration. Decentration of the ablation pattern seems to generate 3rd
      order aberrations. (3) This result is important for the design of customized
      ablation algorithms, which should cancel existing preoperative aberrations while
      avoiding the generation of new aberrations.

PMID- 11328758
TI  - Variability components of standard automated perimetry and frequency-doubling
      technology perimetry.
AB  - PURPOSE: To evaluate and compare intra- and intertest variability components for
      both standard automated perimetry (SAP) and frequency-doubling technology (FDT)
      perimetry in a small group of normal individuals and patients with glaucoma.
      METHODS: The method of constant stimuli (MOCS) was used to examine matched test
      locations with both SAP and FDT perimetry stimuli in a group of eight normal
      individuals and seven patients with glaucoma. Subjects were tested weekly at
      three predetermined visual field loci for 5 consecutive weeks. Frequency-of
      seeing (FOS) curves were generated and used to quantify threshold sensitivity
      (50% seen on FOS, in decibels), intratest variability (FOS interquartile range,
      in decibels), and intertest variability (interquartile range of weekly repeated
      threshold determinations, in decibels). RESULTS: In patients with glaucoma, SAP
      intra- and intertest variabilities were found to increase with sensitivity
      reductions, as previously reported. FDT perimetry revealed that both intra- and
      intertest variability components did not appreciably change with reductions in
      sensitivity. With the measurement scales used in this investigation, both intra-
      and intertest variability components were significantly greater for SAP than for
      FDT perimetry (P < 0.001 and P = 0.003, respectively). Intratest variability
      exceeded intertest variability for both SAP (P = 0.001) and FDT perimetry (P <
      0.001). CONCLUSIONS: For both SAP and FDT perimetry, variability occurring within
      a single test session contributed more to total variability than between-session
      variability. When the measurement scales available on commercial instrumentation
      were used, FDT perimetry exhibited significantly less variability than SAP,
      especially within regions of visual field sensitivity loss. FDT perimetry
      therefore shows promise as an effective test for detecting progressive
      glaucomatous visual field loss, although prospective longitudinal validation is
      still required to determine sensitivity to change.

PMID- 11328759
TI  - Activity of phenothiazines against antibiotic-resistant Mycobacterium
      tuberculosis: a review supporting further studies that may elucidate the
      potential use of thioridazine as anti-tuberculosis therapy.
AB  - The in vitro and in vivo anti-mycobacterial activities of a number of
      phenothiazine compounds are reviewed. These compounds, normally employed for the
      management of psychosis, inhibit the growth in vitro of Mycobacterium
      tuberculosis at concentrations that are significantly greater than those that can
      safely be achieved in a patient harbouring these infections. Nevertheless, one of
      these phenothiazines, chlorpromazine, is concentrated by human macrophages to 10
      100 times its concentration in plasma, and has activity against mycobacteria that
      have been phagocytosed by these cells. Phenothiazines have significant in vitro
      activity against susceptible, polydrug- and multidrug-resistant strains of M.
      tuberculosis, as well as enhancing the activity of some agents employed for first
      line treatment. Because thioridazine, the very mild anti-psychotic agent whose
      most common side effect is drowsiness, has equal anti-tuberculosis properties in
      vitro to chlorpromazine, we recommend that thioridazine be studied as an adjuvant
      to the four- or five-drug regimens employed for the management of a freshly
      diagnosed tuberculosis infection of unknown antibiotic susceptibility, at least
      during the period required for the assessment of antibiotic susceptibility.
      Because it also enhances the activity of rifampicin and streptomycin, antibiotics
      that frequently have adverse effects, additional studies evaluating the use of
      thioridazine as an adjuvant may eventually allow a reduction in the dosages of
      these antibiotics and result in a decreased frequency of adverse effects. It is
      important to note that whereas the management of patients with thioridazine for
      periods in excess of many months will result in the appearance of some
      undesirable side effects, its use for a limited period of 2-3 months should not
      produce side effects that are more severe than simple drowsiness. Nevertheless,
      further in vitro and in vivo studies are essential before thioridazine may be
      recommended for the management of select cases of pulmonary tuberculosis.

PMID- 11328760
TI  - HWY-289, a novel semi-synthetic protoberberine derivative with multiple target
      sites in Candida albicans.
AB  - The antifungal properties of 515 synthetic and semi-synthetic protoberberines
      were investigated. HWY-289 was chosen for further study because it exhibited the
      most significant anti-Candida activity (MICs were 1.56 mg/L for Candida albicans
      and Candida krusei; 6.25 mg/L for Candida guilliermondii) but did not demonstrate
      toxicity in rats. HWY-289 inhibited the incorporation of L-[methyl
      (14)C]methionine into the C-24 of ergosterol in whole cells of C. albicans
      (IC(50) 20 microM). However, HWY-289 (100 microM) had no effect on mammalian
      cholesterol biosynthesis in rat microsomes while miconazole (100 microM) was a
      potent inhibitor of cholesterol biosynthesis under identical assay conditions. A
      second major target site for HWY-289 was identified that involves cell wall
      biosynthesis in C. albicans. HWY-289 was a potent inhibitor of the chitin
      synthase isozymes CaCHS1 and CaCHS2, with IC(50) values of 22 microM for each
      enzyme. The effect was highly specific in that HWY-289 had no significant effect
      on C. albicans CaCHS3 (IC(50) > 200 microM). Thus, HWY-289 compared favourably
      with well-established antifungal agents as an inhibitor of the growth of Candida
      species in vitro, and may have considerable potential as a new class of
      antifungal agent that lacks toxic side effects in the human host.

PMID- 11328761
TI  - Comparison of Etest and a tablet diffusion test with the NCCLS broth
      microdilution method for fluconazole and amphotericin B susceptibility testing of
      Candida isolates.
AB  - Three methods were compared for the susceptibility testing of yeast isolates to
      fluconazole and amphotericin B: two fagar diffusion methods (Etest and a tablet
      diffusion test) and the National Committee for Clinical Laboratory Standards
      (NCCLS) broth microdilution method. Given as MIC(50)s (range), fluconazole
      endpoints were: for the 24 h broth microdilution test, 0.25 mg/L (0.06-32 mg/L);
      for the Etest, 0.38 mg/L (0.064-24 mg/L); and for the NCCLS broth microdilution
      test, 2 mg/L (0.06->or=64 mg/L). With breakpoints of <3 mg/L for susceptible and
      >16 mg/L for resistant, the Etest and the 24 h microdilution test classified the
      isolates in agreement with the classification obtained by the NCCLS method.
      Results obtained by Etest were in closer NCCLS method than those obtained with
      the tablet test. Amphotericin B endpoints were lower for the 24 h microdilution
      and Etests than MICs obtained by the NCCLS broth microdilution method.
      Reproducibility was high for all tests; however, disadvantages of both diffusion
      tests were microcolonies in the inhibition zone and dependence on stringent
      standardization of inoculum.

PMID- 11328762
TI  - Mechanisms of fluconazole resistance in Candida albicans isolates from Japanese
      AIDS patients.
AB  - Four Candida albicans isolates, TIMM 3163, TIMM 3164, TIMM 3165 and TIMM 3166,
      with reduced fluconazole susceptibility were obtained from three AIDS patients in
      Japan, and the mechanisms of their drug resistance were studied. All isolates
      showed lower levels of intracellular accumulation of fluconazole than ATCC 10231,
      a susceptible control strain of C. albicans. Increased amounts of CDR1 and CDR2
      mRNA encoding putative ATP binding cassette (ABC) transporters were associated
      with the azole resistance of all TIMM isolates, apart from TIMM 3164. In
      addition, increased Cdr1p levels were immunodetected in the cell membrane
      fractions of all the TIMM strains except for TIMM 3164. Gene amplification was
      not responsible for CDR1 overexpression and there were no significant differences
      in the mRNA levels of CDR3 or CDR4 (ABC transporters) in the azole-susceptible
      and -resistant cells. CaMDR1 (a major facilitator superfamily) gene expression
      was not observed in any of the resistant isolates or the control strain. These
      results suggest that energy-dependent drug efflux associated with increased
      expression of CDR1 and CDR2 is involved in the fluconazole resistance mechanisms
      in two of the four isolates, TIMM 3165 and TIMM 3166. TIMM 3164 demonstrated
      energy-dependent drug efflux without overexpression of CDR1-4 or CaMDR1,
      indicating that some other pump may be operating. Despite showing low levels of
      drug efflux and overexpression of CDR1 and CDR2, efflux in TIMM 3163 was not
      energy dependent, suggesting that the expressed Cdr1p non-functional Cdr1p and
      that other resistance mechanisms may operate in this strain.

PMID- 11328763
TI  - Mechanism of action of anti-proliferative lysophospholipid analogues against the
      protozoan parasite Trypanosoma cruzi: potentiation of in vitro activity by the
      sterol biosynthesis inhibitor ketoconazole.
AB  - We investigated the mechanism of action of metabolically stable lysophospholipid
      analogues (LPAs), with potent anti-tumour and anti-protozoal activity against
      Trypanosoma cruzi, the causative agent of Chagas' disease. Against the axenically
      grown epimastigote form of the parasite, the IC(50)s after 120 h for ET-18
      OCH(3), miltefosine and ilmofosine were 3, 1 and 3 microM, respectively; at
      higher concentrations immediate lytic effects were observed. Eradication of the
      intracellular amastigote, grown inside Vero cells, was achieved at 0.1, 0.1 and 1
      microM for ET-18-OCH(3), miltefosine and ilmofosine, respectively. Analysis of
      the lipid composition of epimastigotes exposed to LPAs at their IC(50) for 120 h
      showed that the ratio of phosphatidyl-choline (PC) to phosphatidylethanolamine
      (PE) changed from 1.5 in control cells to c. 0.67 in those treated with the
      analogues. A significant increase in the content of phosphatidylserine was also
      observed in treated cells. Intact epimastigotes efficiently incorporated
      radioactivity from L-[methyl-(14)C]methionine into PC, but not from [methyl
      (14)C]choline. ET-18-OCH(3) inhibited the incorporation of L-[methyl
      (14)C]methionine into PC with an IC(50) of 2 microM, suggesting that inhibition
      of the de novo synthesis through the Greenberg's pathway was a primary effect
      underlying the selective anti-parasitic activity of this compound.
      Antiproliferative synergism was observed as a consequence of combined treatment
      of epimastigotes with ET-18-OCH(3) and ketoconazole, a sterol biosynthesis
      inhibitor, probably due to the fact that a secondary effect of the latter is also
      a blockade of PC synthesis at the level of PE-PC-N-methyl-transferase.

PMID- 11328764
TI  - Amino acid substitutions causing inhibitor resistance in TEM beta-lactamases
      compromise the extended-spectrum phenotype in SHV extended-spectrum beta
      lactamases.
AB  - Three amino acid substitutions, Met-69-->Ile, Arg-244-->Ser and/or Asn-276-->Asp,
      mediate inhibitor resistance (IR) in TEM beta-lactamases. They were introduced in
      all possible combinations at homologous positions into either SHV-1 or the
      respective extended-spectrum beta-lactamases (ESBLs), SHV-2 or SHV-5.
      Susceptibility testing of the resulting set of seven variants of each parental
      strain, all in an isogenic background, was performed. The phenotypes of the
      constructions revealed that most substitutions resulted in reduced resistance to
      most tested single beta-lactam formulations. This decrease over-compensated for
      the expected increase in inhibitor resistance, so that most mutants showed no
      rise in resistance to inhibitor/beta-lactam combinations, although increases of
      MICs from one- to 43-fold compared with the respective parental strains were also
      measured. Combination of several IR-determining substitutions impaired both
      phenotypes in the carrier strains even more. None of the 14 mutants derived from
      the ESBLs, SHV-2 and SHV-5, showed a clinically relevant combined ESBL-IR
      phenotype. These findings indicate that the SHV beta-lactamase does not benefit
      proportionally from simultaneous substitution of residues relevant for the ESBL
      and the IR phenotype.

PMID- 11328765
TI  - Antibiotic susceptibility of attached and free-floating Helicobacter pylori.
AB  - Helicobacter pylori are found attached to mucous cells of the human stomach or
      under the mucous layer. Models mimicking the in vivo situation may be more
      suitable for H. pylori MIC determinations than traditional agar dilution methods.
      Megraud et al. (Antimicrobial Agents and Chemotherapy 1991, 35, 869-72) developed
      a model for measuring the susceptibility of attached and free-floating H. pylori.
      We have modified this model so that free-floating and attached H. pylori are
      treated in a more similar manner, before and after incubation with antibiotic,
      and performed additional controls to ensure H. pylori and tissue culture cells
      are not detrimentally affected and maintain their viability during the course of
      the experiment. We found only 10% of plate-grown H. pylori were competent for
      attachment to HEp-2 cells; however, all progeny of attached bacteria remained
      adherent. Killing curves were performed using 0, 0.001, 0.01, 0.1 and 1 mg/L
      amoxycillin, and 0, 0.0025, 0.0075 and 0.01 mg/L clarithromycin. H. pylori
      divided at concentrations <or= 0.01 mg/L amoxycillin and <or= 0.0025 mg/L
      clarithromycin. Contrary to the previous study, using our modified method we
      found that HEp-2 adherent and freefloating H. pylori are equally susceptible to
      amoxycillin (strains 26695, CCUG18943, CCUG19104 and CCUG19110) and
      clarithromycin (strain 26695). Therefore, we find no evidence that attachment of
      H. pylori to eukaryotic cells increases their resistance to antibiotics compared
      with non-attached bacteria. Nonetheless, these results confirm confidence in
      traditional MIC studies when a comparison is made between susceptible and
      resistant strains.

PMID- 11328766
TI  - Antibacterial activity of essential oils and their major constituents against
      respiratory tract pathogens by gaseous contact.
AB  - The antibacterial activity of 14 essential oils and their major constituents in
      the gaseous state was evaluated against Haemophilus influenzae, Streptococcus
      pneumoniae, Streptococcus pyogenes and Staphylococcus aureus. For most essential
      oils examined, H. influenzae was most susceptible, followed by S. pneumoniae and
      S. pyogenes, and then S. aureus. Penicillin-susceptible and -resistant S.
      pneumoniae were comparable in susceptibility. Escherichia coli, which was used as
      a control, showed least susceptibility. A minimal inhibitory dose (MID) was
      introduced as a measure of the vapour activity. Among 14 essential oils, cinnamon
      bark, lemon-grass and thyme oils showed the lowest MID, followed by essential
      oils containing terpene alcohols as major constituents. The essential oils
      containing terpene ketone, ether and, in particular, hydrocarbon had high MIDS.
      The vapour activity on short exposure was comparable to that following overnight
      exposure, and rapid evaporation was more effective than slow evaporation of
      essential oils. The vapour concentration and absorption into agar of essential
      oils reached a maximum 1 or 2 h after rapid evaporation. These results indicate
      that the antibacterial action of essential oils was most effective when at high
      vapour concentration for a short time.

PMID- 11328767
TI  - In vitro activity of PR-39, a proline-arginine-rich peptide, against susceptible
      and multi-drug-resistant Mycobacterium tuberculosis.
AB  - We have investigated the in vitro activity of antimicrobial peptides against
      Mycobacterium tuberculosis using a radiometric method and cfu determinations. PR
      39, a proline-arginine-rich antibacterial peptide from porcine leucocytes, was
      found to be active against drug-susceptible as well as multi-drug-resistant (MDR)
      clinical isolates of M. tuberculosis. The activity of PR-39 was concentration
      dependent, with 80% growth inhibition of M. tuberculosis H37Rv at 50 mg/L. The
      MDR M. tuberculosis strains E1380/94 and P34/95 were less susceptible to PR-39,
      with 39 and 49% growth inhibition at 50 mg/L peptide, respectively, suggesting a
      lower susceptibility than strain H37Rv and drug-susceptible clinical isolates.
      Reduction of counts of M. tuberculosis H37Rv and the MDR M. tuberculosis strain
      E1380/94 by PR-39 indicated that the growth inhibition seen in the radiometric
      assay is due to a mycobactericidal effect of the peptide. These observations
      suggest that antimicrobial peptides may play an important role in host defence
      against MDR M. tuberculosis.

PMID- 11328768
TI  - The activity of 14-hydroxy clarithromycin, alone and in combination with
      clarithromycin, against penicillin- and erythromycin-resistant Streptococcus
      pneumoniae.
AB  - There are no data regarding the activity of clarithromycin's active metabolite,
      14-hydroxy clarithromycin, against penicillin-intermediate, penicillin-resistant
      or erythromycin-resistant Streptococcus pneumoniae. Agar dilution MICs were
      determined for clarithromycin, 14-hydroxy clarithromycin (henceforth called
      'metabolite'), azithromycin, erythromycin and clarithromycin/metabolite (2:1 and
      1:1 ratio) against 24 penicillin-intermediate and 14 penicillin-resistant
      strains, including 13 erythromycin-resistant clinical strains and one ATCC strain
      of S. pneumoniae. The interaction between clarithromycin and its metabolite was
      determined using an agar chequerboard assay against all isolates, and time-kill
      tests were performed against five penicillin-intermediate (macrolide-susceptible)
      and five penicillin-resistant (two macrolide-resistant) strains of S. pneumoniae
      using all antibiotics alone at simulated peak serum concentrations, and
      clarithromycin/metabolite in a 2:1 ratio (physiological). MICs were as follows:
      clarithromycin, 0.008-->64 mg/L; metabolite, 0.015-->64 mg/L; erythromycin, 0.015
      ->64 mg/L; azithromycin, 0.125-->64 mg/L; clarithromycin/metabolite (1:1 and 2:1
      combinations), 0.001-->64 mg/L. The MIC of the clarithromycin/metabolite
      combination was one or more tube dilution lower than the MIC of clarithromycin in
      28 of the isolates tested. In chequerboard testing, 13 strains (seven
      erythromycin susceptible and six erythromycin resistant) demonstrated synergy, 18
      additivity and seven indifference. In time-kill testing, bacterial eradication
      below detection limits occurred with clarithromycin and metabolite in seven of 10
      organisms. The combination of parent and metabolite was more rapidly bactericidal
      than clarithromycin alone in six of the seven isolates (P = 0.026). The
      metabolite has potent activity against S. pneumoniae and enhances the activity of
      the parent compound against this organism. The metabolite's activity must be
      considered in evaluating clarithromycin in vitro to avoid underestimation of
      clarithromycin's activity against the pneumococcus.

PMID- 11328769
TI  - In vitro evaluation of the risk of developing bacterial resistance to antiseptics
      and antibiotics used in medical devices.
AB  - The risk of development of resistance in Staphylococcus epidermidis to the
      antibiotics and antiseptics impregnated in central venous catheters was
      evaluated. The culture was passaged 10-20 times through subinhibitory
      concentrations of different antimicrobials, singly and in combination, and the
      MIC of each antimicrobial before and after passage was compared. There was a 10-
      to 16-fold increase in the MIC of the combination of minocycline and rifampicin,
      while no significant increase in the MIC of minocycline alone was seen. The MIC
      of rifampicin was 25,000-fold higher against strains passaged through rifampicin
      alone (as compared with that for the original strain), while the increase was
      only 80-fold when it was combined with minocycline for passage. There was no
      substantial change in susceptibility to the antiseptic chlorhexidine when used
      alone or in combination with either silver sulphadiazine or triclosan (the MIC of
      triclosan alone increased eight-fold). In time-kill studies, synergy was observed
      between chlorhexidine and both triclosan and silver sulphadiazine. Zone of
      inhibition tests of catheters impregnated with minocycline and rifampicin showed
      that their activity against rifampicin-resistant strains was lower than that
      against the susceptible strain. On the other hand, the activity of the antiseptic
      (chlorhexidine and silver sulphadiazine) catheters against the rifampicin
      resistant and -susceptible strains was similar. Although this study indicates
      that antibiotic catheters may be at a higher risk of being colonized by
      antibiotic-resistant bacteria, the implications of these results in clinical
      settings need to be determined.

PMID- 11328770
TI  - The prevalence of trimethoprim-resistance-conferring dihydrofolate reductase
      genes in urinary isolates of Escherichia coli in Korea.
AB  - One-hundred and twenty-two urinary isolates of Escherichia coli were studied for
      trimethoprim resistance. Seventy-seven (63.1%) of the 122 isolates were found to
      be resistant to trimethoprim. Of the 77 trimethoprim-resistant isolates, 75 dfr
      genes were detected in 72 isolates as follows: the dfrA17 gene was the most
      prevalent, being found in 27 isolates, followed by dfrA12 in 26, dfrA1 in 15,
      dfrA5 in four and dfrA7 in three. Southern blot and PCR mapping analysis revealed
      that all of the dfrA17, dfrA12, dfrA5 and dfrA7 genes were located on class 1
      integrons. The dfrA1 gene inserted as a gene cassette in class 1 integrons was
      found in 10 of 15 isolates, and the intI2 gene of Tn7 was detected in two out of
      five isolates. In conjugation experiments, the dfr genes inserted in class 1
      integrons were transferred to a recipient E. coli in 32 (42.7%) of the 75 dfr
      genes. In conclusion, the dfrA17 and dfrA12 genes were the most prevalent genes
      responsible for trimethoprim resistance in urinary tract isolates of E. coli from
      Korea and the dfr genes inserted in integrons are more widespread than those that
      are not related to gene cassettes.

PMID- 11328771
TI  - Carriage of antibiotic-resistant bacteria by healthy children.
AB  - The frequency of carriage of antibiotic-resistant bacteria in healthy 7- and 8
      year-old children in Bristol was studied. Children born in Avon between 1 April
      1991 and 31 December 1992, attending the Avon Longitudinal Study of Pregnancy and
      Childhood (ALSPAC) 7 year follow-up clinic, formed the study population. Carriage
      was estimated using mouth and stool samples. None of 105 children on whom
      information was available had received tetracycline, chloramphenicol,
      ciprofloxacin or an extended-spectrum cephalosporin in the previous year.
      Staphylococcus aureus was isolated from mouthwashes from 200 (37.1%) of 539
      children sampled. Six (3%) of the isolates were resistant to chloramphenicol or
      tetracycline and four (2%) were methicillin resistant. Haemophilus spp. were
      isolated from 369 (72%) of 513 samples and 63 (17%) were ampicillin resistant, 49
      (13.3%) were erythromycin resistant and seven (1.9%) were tetracycline resistant.
      Branhamella catarrhalis was isolated from 333 (74%) of 450 samples. Twenty-eight
      (8.4%) were erythromycin resistant and 14 (4.2%) strains were tetracycline
      resistant. Group A beta-haemolytic streptococci were isolated from 17 of 507
      children sampled. One (5.9%) was tetracycline resistant. Stool samples were
      returned from 335 (62%) of 539 children from whom they were requested. Eleven per
      cent of samples yielded Gram-negative bacilli with high-level resistance to
      chloramphenicol, which was frequently linked to resistance to ampicillin,
      spectinomycin and streptomycin. Isolates demonstrating resistance to the third
      generation cephalosporin ceftazidime were recovered from 17 subjects (3.2%). Six
      (35%) of 17 isolates possessed extended-spectrum beta-lactamases. Healthy
      children carry bacteria resistant to antibiotics to which children are not
      usually exposed. Resistance to ceftazidime, chloramphenicol and tetracycline may
      be co-selected by exposure to other antibiotics used in children or may be
      acquired from family members, pets, other children or food. These results suggest
      that antibiotic-resistant bacteria are widely disseminated and may be acquired by
      children before exposure to specific selection pressure.

PMID- 11328772
TI  - Cerebrospinal fluid penetration and pharmacokinetics of levofloxacin in an
      experimental rabbit meningitis model.
AB  - This study was designed to investigate the penetration across the blood-brain
      barrier of three doses of levofloxacin using a microdialysis probe implanted into
      the cerebrospinal fluid (CSF) of a rabbit pneumococcal meningitis model. The
      microdialysis guide cannula was implanted into rabbit subarachnoid space using a
      stereotaxic frame. After 3 days, 10(4) cfu Streptococcus pneumoniae serotype 3 in
      0.3 mL saline was injected via intracisternal puncture and animals were allowed
      to incubate the organisms for 16-18 h. Groups of animals (n = 5) then received 7,
      10.5 or 14 mg/kg iv of the drug over 10 min. Plasma samples were obtained via an
      ear vein 0, 0.25, 0.5, 0.75, 1, 2, 4, 6 and 8 h after the antibiotic infusion.
      CSF microdialysis effluent samples were collected every 0.5 h for the entire
      experiment. Plasma and microdialysis effluent samples were analysed by HPLC.
      AUC(0-8) in plasma and CSF were computed using the trapezoid rule. The
      elimination half-life in plasma and CSF was calculated using non-linear
      regression analysis. The unbound peak plasma concentrations for the three doses
      studied were 3.9, 6.4 and 10.3 mg/L, respectively. There was a significant
      increase in the plasma AUC(0-8) [29.7 +/- 6.3, 49.1 +/- 19.1 and 67.6 +/- 8.9 mg
      x h/L (P < 0.005)]. The unbound peak CSF concentrations were 3.8, 5.7 and 8.6
      mg/L and occurred at 0-0.5 h after the administration of the dose. The AUC(CSF(0
      8)) was significantly higher as the dose was increased (7 mg/kg, 15.8 +/- 6.6;
      10.5 mg/kg, 37.3 +/- 7.8; and 14 mg/kg, 46.4 +/- 20.9 mg x h/L; P < 0.03). The
      penetration of levofloxacin averaged 53% for the 7 mg/kg dosage group, 76% for
      the 10.5 mg/kg group and 68% for the 14 mg/kg group. Our results demonstrate that
      levofloxacin penetration into the CSF averages 66% for the doses that would be
      used in clinical practice.

PMID- 11328773
TI  - In vivo efficacy of continuous infusion versus intermittent dosing of ceftazidime
      alone or in combination with amikacin relative to human kinetic profiles in a
      Pseudomonas aeruginosa rabbit endocarditis model.
AB  - Ceftazidime and amikacin were administered in a Pseudomonas aeruginosa rabbit
      endocarditis model using computer-controlled intravenous (iv) infusion pumps to
      simulate human serum concentrations for the following regimens: continuous
      (constant rate) infusion of 4, 6 or 8 g of ceftazidime over 24 h or intermittent
      dosing of 2 g every 8 h either alone or in combination with amikacin (15 mg/kg
      once daily). The in vivo activities of these regimens were tested on four
      Pseudomonas aeruginosa strains. Animals were killed 24 h after the beginning of
      treatment. Efficacy was assessed by comparing the effects of the different groups
      on bacterial counts in vegetations for each strain tested. For a susceptible
      reference strain (ATCC 27853; MICs of ceftazidime and amikacin 1 and 2 mg/L,
      respectively), continuous infusion of 4 g alone or with amikacin was as effective
      as intermittent dosing with amikacin. For a clinical isolate producing an
      oxacillinase (MICs of ceftazidime and amikacin 8 and 32 mg/L, respectively),
      continuous infusion of 6 g was equivalent to intermittent dosing. For a clinical
      isolate producing a TEM-2 penicillinase (MIC of ceftazidime and amikacin 4 mg/L),
      continuous infusion of 6 g, but not intermittent dosing, had a significant in
      vivo effect. For a clinical isolate producing an inducible, chromosomally encoded
      cephalosporinase (MIC of ceftazidime and amikacin 8 and 4 mg/L, respectively),
      neither continuous infusion nor intermittent dosing proved effective.
      Determination of ceftazidime concentrations in vegetations showed that continuous
      infusion produced tissue concentrations at the infection site far greater than
      the MIC throughout the treatment. It is concluded that continuous infusion of the
      same total daily dose provides significant activity as compared with fractionated
      infusion. This study confirms that a concentration of 4-5 x MIC is a reasonable
      therapeutic target in most clinical settings of severe P. aeruginosa infection.

PMID- 11328774
TI  - Comparative study of treatment with penicillin, ceftriaxone, trovafloxacin,
      quinupristin-dalfopristin and vancomycin in experimental endocarditis due to
      penicillin- and ceftriaxone-resistant Streptococcus pneumoniae.
AB  - The efficacy of different antibiotics was compared in an experimental model of
      aortic valve endocarditis in rabbits, using a serotype 19 strain of Streptococcus
      pneumoniae resistant to penicillin (MIC 12 mg/L) and ceftriaxone (MIC 12 mg/L).
      The results were compared with those of a control group, which received no
      treatment. One hundred and nineteen animals were treated with one of the
      following antibiotic regimens: im procaine penicillin G at a dosage of 300,000
      U/kg weight/12 h (16 animals); iv trovafloxacin, 13.3 mg/kg/12 h (31 animals); iv
      ceftriaxone, 75 mg/kg/24 h (21 animals); iv vancomycin, 20 mg/kg/12 h (15
      animals) and im quinupristin-dalfopristin, 30 mg/kg/8 h (20 animals). All the
      antibiotics used in this study proved to be efficient in reducing numbers of S.
      pneumoniae and in increasing the percentage of aortic vegetations that were
      rendered sterile compared with the control group. Penicillin at the dosage used
      in our study was capable of achieving serum concentrations two or three times
      greater than the MIC, thus demonstrating its effectiveness as an antibiotic for
      this endocarditis model. No significant difference was observed between the
      effects of vancomycin, quinupristin-dalfopristin and penicillin. Vancomycin
      proved to be more efficient than trovofloxacin in reducing the bacterial load and
      increasing the numbers sterilized. There was also a tendency for this antibiotic
      to be more effective than ceftriaxone in reducing the bacterial load of the
      vegetations. There was a statistically significant correlation between the weight
      of the vegetations and their bacterial load. In the light of these results,
      vancomycin and quinupristin-dalfopristin may be considered suitable alternatives
      to penicillin for the treatment of penicillin-resistant S. pneumoniae
      endocarditis.

PMID- 11328775
TI  - Therapeutic possibilities of long-term roxithromycin treatment for chronic
      diffuse sclerosing osteomyelitis of the mandible.
AB  - The clinical efficacy of long-term roxithromycin treatment was examined
      objectively in nine patients with chronic diffuse sclerosing osteomyelitis of the
      mandible. Roxithromycin was administered orally at a dose of 300 mg/day for
      between 68 days and 66 months. In seven of the nine cases (77.8%), the symptoms
      disappeared 1-12 months after the start of therapy. Radiography showed that
      osteolytic changes (evident from 'moth-eaten' appearance of bone) had improved
      but that osteosclerosis had persisted or become more predominant by the end of
      therapy. Therefore, the optimum duration of treatment should be decided according
      to the amelioration of symptoms along with the disappearance of osteolytic
      findings in radiographs. Diarrhoea and stomach discomfort occurred in one case,
      and liver dysfunction in another, but these adverse reactions were relatively
      mild. The mechanism of action of roxithromycin in this study is not yet fully
      understood, but our results indicate that long-term roxithromycin treatment may
      be useful for diffuse sclerosing osteomyelitis of the mandible and should be
      attempted before surgical treatment is considered.

PMID- 11328776
TI  - Successful administration of quinupristin/dalfopristin in the outpatient setting.
AB  - Intravenous administration of quinupristin/dalfopristin outside the hospital
      setting has not been reported previously. We describe 37 outpatients receiving
      quinupristin/dalfopristin iv for infections including osteomyelitis, bacteraemia,
      abscesses and cellulitis. The most frequent aetiological pathogens found were
      Enterococcus faecium, Staphylococcus aureus and coagulase-negative staphylococci.
      Patients received an average of 9 days therapy as inpatients and 22 days as
      outpatients. Quinupristin/dalfopristin was administered using various access
      devices, most commonly peripherally inserted central catheters and tunnelled
      central catheters. The bacteriological and clinical success rates were both
      89.2%. Five patients were readmitted to hospital; one patient developed catheter
      related bacteraemia. The most frequently reported non-venous adverse events were
      nausea (18.9% of patients), myalgia (18.9%) and arthralgia (13.5%). Sixteen
      patients experienced venous access-related events, most commonly infusion pain,
      oedema and phlebitis. In this group of patients, for those who had difficult-to
      treat infections, intravenous quinupristin/dalfopristin therapy was generally
      effective and safe outside the hospital setting.

PMID- 11328777
TI  - Mutation frequencies for resistance to fusidic acid and rifampicin in
      Staphylococcus aureus.
AB  - Frequencies at which mutants resistant to fusidic acid and/or rifampicin arose in
      vitro were determined in Staphylococcus aureus strains including methicillin
      susceptible S. aureus (MSSA), methicillin-resistant S. aureus (MRSA), vancomycin
      intermediate resistant S. aureus (VISA) and hetero-VISA. The concentrations of
      fusidic acid (30 and 15 mg/L) and rifampicin (16 and 1 mg/L) used for selection
      were equal to the expected maximum and minimum serum concentrations after an oral
      regimen of rifampicin 900 mg od, together with fusidic acid 500 mg tds. Resistant
      mutants arose at a frequency of around 10(-8) for selections with rifampicin, but
      were undetectable (frequency <10(-11)) for selections with fusidic acid. Mutants
      were not recovered (frequency <10(-11)) after selections in the presence of both
      fusidic acid and rifampicin at 30/16 and 15/1 mg/L. Our results suggest that
      these antibiotics, when used in combination, could have a wider role in the
      management of staphylococcal infections.

PMID- 11328778
TI  - Decreased susceptibility to azithromycin and erythromycin mediated by a novel
      mtr(R) promoter mutation in Neisseria gonorrhoeae.
AB  - During a screen of Neisseria gonorrhoeae clinical isolates obtained in Uruguay
      for susceptibility to azithromycin, we noticed that approximately 10% of the
      strains examined displayed decreased susceptibility to azithromycin and
      erythromycin due to the mtr(CDE)-encoded efflux pump system, but remained
      susceptible to Triton X-100. We now report that the mtr(R) promoter region of one
      of these isolates contains a dinucleotide insertion (TT) that mediates this
      resistance phenotype.

PMID- 11328779
TI  - Target site modifications and efflux phenotype in clinical isolates of
      Streptococcus pneumoniae from Hong Kong with reduced susceptibility to
      fluoroquinolones.
AB  - Ciprofloxacin-susceptible (n = 7) and -resistant (MIC >or=4 mg/L) (n = 15)
      clinical isolates of Streptococcus pneumoniae from diverse sources in Hong Kong
      were studied for target site modifications and efflux phenotype. Reserpine
      inhibited efflux of ciprofloxacin and/or levofloxacin was common in both
      susceptible and non-susceptible isolates. The ParC substitutions K137N and/or
      S79F or Y were associated with increased ciprofloxacin MICS. The GyrA
      substitution S81F was only found in isolates with full resistance to
      ciprofloxacin (MIC >or=16 mg/L) and levofloxacin (MIC >or=8 mg/L). Among clinical
      isolates of S. pneumoniae, accumulation of target site mutations in strains with
      an efflux mechanism was associated with increasing MICs of fluoroquinolones.

PMID- 11328780
TI  - In vitro activity of antimicrobial agents against the endosymbiont Wolbachia
      pipientis.
AB  - Arthropod-transmitted (filarial) nematodes are important causes of disease in
      humans in tropical countries, yet no safe drug appropriate for mass delivery
      kills the adult worms. However, most filarial nematodes contain rickettsia-like
      bacteria of the genus Wolbachia, and related bacteria also occur in insects.
      There is increasing evidence that these bacteria have significant functions in
      the biology of filarial nematodes. They are thus important targets in the search
      for antifilarial drugs and experiments in animals and humans have suggested that
      antibiotic therapy has potential in treating filarial infections. To optimize
      future clinical trials there is a need for a fast and simple in vitro drug screen
      to compare drug efficacies against Wolbachia. In the absence of Wolbachia
      infected nematode cell lines, we have utilized an Aedes albopictus insect cell
      line, naturally infected with Wolbachia, to test the activity of antimicrobial
      agents. Of the five antibiotics tested, doxycycline, oxytetracycline and
      rifampicin showed good activity (MICs of 0.0625, 4 and 0.0625 mg/L, respectively)
      whereas ciprofloxacin and penicillin were shown to have no effect.

PMID- 11328781
TI  - In vitro activity of garlic oil and four diallyl sulphides against antibiotic
      resistant Pseudomonas aeruginosa and Klebsiella pneumoniae.
AB  - The in vitro antibacterial activities of garlic oil and four diallyl sulphides
      naturally occurring in this oil were studied against Pseudomonas aeruginosa and
      Klebsiella pneumoniae (total 237 clinical isolates). Garlic oil at 4 x MIC could
      reduce original inoculum to <or=2 log(10) in both P. aeruginosa and K. pneumoniae
      within 8 h. The MIC values of four diallyl sulphides against these two pathogens
      followed the order diallyl monosulphide > diallyl disulphide > diallyl
      trisulphide (DAT) > diallyl tetrasulphide (DATS) (P < 0.05). Most interactions of
      ceftazidime, gentamicin, imipenem and meropenem with DAT or DATS, determined
      according to the fractional inhibitory concentration index, showed synergic or
      additive effects. These results suggest that garlic oil, DAT and DATS may have
      potential for the prevention or treatment of nosocomial, antibiotic-resistant
      bacterial infections.

PMID- 11328782
TI  - Activities of cholic acid-derived antimicrobial agents against multidrug
      resistant bacteria.
AB  - Cationic cholic acid derivatives displayed potent and broad-spectrum activity
      against multidrug-resistant Gram-negative and -positive bacteria. Specific
      examples were effective permeabilizers of the outer membranes of many strains of
      multidrug-resistant Gram-negative bacteria and sensitized these to hydrophobic
      antibiotics. We also prepared a new cholic acid derivative with improved apparent
      selectivity for prokaryote membranes.

PMID- 11328783
TI  - In vitro activity of linezolid and 11 other antimicrobials against 566 clinical
      isolates and comparison between NCCLS microdilution and Etest methods.
AB  - The in vitro activity of linezolid and 11 other antimicrobials was determined for
      566 clinical isolates of Staphylococcus aureus, Staphylococcus epidermidis,
      Enterococcus spp., Streptococcus pyogenes, Streptococcus agalactiae,
      Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis, some
      of them resistant to several antibiotics, using a broth microdilution method and
      the Etest method. All Gram-positive organisms tested were inhibited by a
      concentration of <or=4 mg/L of linezolid, including methicillin-resistant
      staphylococci, vancomycin- and ampicillin-resistant enterococci, and penicillin
      intermediate and -resistant pneumococci. MICs of linezolid by the Etest method
      were usually one to two dilution values lower than those obtained by
      microdilution.

PMID- 11328784
TI  - Comparative in vitro activity of the new quinolone gemifloxacin (SB-265805) with
      other fluoroquinolones against respiratory tract pathogens.
AB  - The in vitro activity of gemifloxacin (SB-265805) was compared with that of other
      fluoroquinolones against 302 clinical isolates of Streptococcus pneumoniae, 300
      clinical isolates of Haemophilus influenzae and 28 clinical isolates of Moraxella
      catarrhalis, including multiply resistant strains. Gemifloxacin at 0.12 mg/L
      inhibited all microorganisms tested. MIC(90) values of gemifloxacin,
      trovafloxacin, grepafloxacin and levofloxacin against all (630) isolates tested
      were 0.03, 0.12, 0.12 and 1 mg/L, respectively. MIC(90) values of the same
      fluoroquinolones against S. pneumoniae were 0.06, 0.25, 0.12 and 1 mg/L,
      respectively.

PMID- 11328785
TI  - SHV-type extended-spectrum beta-lactamase in a Shigella flexneri clinical
      isolate.
AB  - A Shigella flexneri isolate resistant to oxyimino-cephalosporins was recovered
      from a stool sample of a 16 month-old Algerian child hospitalized in Paris,
      France. This isolate harboured an SHV-2 beta-lactamase gene located on a c. 80 kb
      self-transferable plasmid. This is the first report of an Ambler class A extended
      spectrum beta-lactamase from Shigella spp.

PMID- 11328787
TI  - Antimicrobial susceptibility of blood culture isolates of viridans streptococci:
      relationship to a change in empirical antibiotic therapy in febrile neutropenia.
AB  - This study investigated the antibiotic susceptibilities of 67 isolates of
      viridans streptococci from 61 cases of bacteraemia in immunocompromised
      paediatric patients with malignancy. The majority of patients (87%) had received
      prior courses of empirical antibiotic therapy, which consisted of ceftazidime
      plus amikacin during period 1 and piperacillin/tazobactam plus amikacin during
      period 2. Susceptibility to vancomycin and quinupristin/dalfopristin was 100%.
      Susceptibility to beta-lactam antibiotics varied. For period 1, the geometric
      mean MICs of all beta-lactams tested against blood culture isolates (n = 31)
      exceeded those against isolates (n = 36) collected from blood after the change in
      empirical therapy (by 3.3-fold for ceftazidime, 2.8-fold for
      piperacillin/tazobactam and 1.6-fold for penicillin). The selection of a beta
      lactam antibiotic for empirical therapy must be made with care, as repeated
      courses of certain agents may be more likely to select for viridans streptococci
      with diminished susceptibility.

PMID- 11328786
TI  - Potentially virulent strains and high colony counts of group A beta-haemolytic
      streptococci in pharyngitis patients having a delayed recovery or a complication.
AB  - T serotyping and M and exotoxin genotyping were performed on strains from 367
      streptococcal pharyngitis patients in Dutch general practice. Potentially
      virulent strains of group A beta-haemolytic streptococci, such as T1M1 and T3M3
      subtypes and strains expressing speA and speC, and a high number of colony counts
      did not occur more frequently in the 166 (45%) more seriously ill patients,
      defined as those who showed a delayed recovery or a complication.

PMID- 11328788
TI  - The effect of Escherichia coli heat-stable toxin on the trans-epithelial
      intestinal elimination of ciprofloxacin in the rabbit.
AB  - The effect of Escherichia coli heat-stable toxin (ST) on the intestinal trans
      epithelial elimination of ciprofloxacin was studied in the rabbit model.
      Following a systemic 27 mg/kg dose, excreted amounts of ciprofloxacin during the
      2 h experiment were: 9.3 (+/- 4.8); 12.5 (+/- 5.2) and 0.3 (+/- 0.1) microg/cm(2)
      surface of intestinal wall in ST-challenged jejunal, ileal and caecal loops,
      respectively. In control loops the corresponding amounts were: 5.0 (+/- 2.8), 6.5
      (+/- 3.4) and 0.3 (+/- 0.1) microg/cm(2), respectively. The trans-epithelial
      elimination of ciprofloxacin was significantly higher in ST-challenged small
      bowel loops than in controls while caecal elimination was negligible.

PMID- 11328789
TI  - Efficacy of gatifloxacin alone and in combination with cefepime against
      penicillin-resistant Streptococcus pneumoniae in a rabbit meningitis model and in
      vitro.
AB  - Gatifloxacin penetrated well into cerebrospinal fluid (CSF) (49 +/- 11%),
      measured by comparison of AUC(CSF)/AUC(serum), and showed good bactericidal
      activity (leading to a decrease of 0.75 +/- 0.17 log10 cfu/mL/h) in the treatment
      of experimental meningitis in rabbits caused by a penicillin-resistant
      pneumococcal strain (MIC 4 mg/L). It was significantly more effective than the
      standard regimen, ceftriaxone with vancomycin, which led to a decrease of 0.53 +/
      0.17 log10 cfu/mL/h. The addition of cefepime to gatifloxacin slightly improved
      the killing rates (giving a decrease of 0.84 +/- 0.14 log10 cfu/mL/h). In vitro,
      synergy was demonstrated between cefepime and gatifloxacin by the chequerboard
      method (fractional inhibitory concentration index = 0.5) and by viable counts
      over 8 h.

PMID- 11328790
TI  - Effect of LY333328 against vancomycin-resistant Enterococcus faecium in a rat
      central venous catheter-associated infection model.
AB  - A rat central venous catheter (CVC) infection model was used to assess the
      activity of LY333328 against vancomycin-resistant Enterococcus faecium (VRE). Via
      the CVC, animals were challenged with 10(6) cfu of Enterococcus faecium with the
      VanA phenotype. Eight rats received a single dose of LY333328 and eight rats
      received saline. Seventy-five per cent of control animals had peripheral
      bacteraemia and 87.5% had VRE recovered from explanted CVCs at the time they were
      killed, as compared with 0 and 12.5%, respectively, of the LY333328-treated
      animals (P < 0.01). All animals in the control group had evidence of metastatic
      disease compared with none of the treated group (P < 0.01). LY333328 was
      effective against the strain of VRE tested in this model.

PMID- 11328791
TI  - Suppressive effect of Lactobacillus gasseri OLL 2716 (LG21) on Helicobacter
      pylori infection in humans.
AB  - To examine the efficacy of Lactobacillus gasseri OLL2716 (LG21) as a probiotic
      for Helicobacter pylori in humans, 31 subjects infected with the bacterium
      ingested yogurt containing LG21 daily for an 8 week period. The [(13)C]urea
      breath test and assays of serum pepsinogens revealed a significant improvement
      following LG21 treatment. LG21 was thus determined to be effective in both
      suppressing H. pylori and reducing gastric mucosal inflammation.

PMID- 11328792
TI  - Pancreatic concentrations of cefepime.
AB  - The concentrations of cefepime in pancreatic pseudocyst fluid (n = 4), pancreatic
      tissue (n = 4) and pancreatic fistula fluid (n = 1), and simultaneous plasma
      concentrations, were measured after intravenous administration of a single 2 g
      dose to nine patients. Mean plasma concentration was 27.4 mg/L between 120 and
      200 min after the end of infusion. Mean pancreatic cefepime concentration was 6.3
      mg/L in pseudocyst and 10.7 mg/L in pancreatic tissue. Cefepime was detected by
      30 min after the end of the perfusion in pancreatic fistulae fluid, and persisted
      at 8 h. We conclude that cefepime is a potentially useful antibiotic in
      prevention and treatment of pancreatic infection.

PMID- 11328793
TI  - Effect of inoculum form on in vitro antifungal susceptibilities of Aspergillus
      spp.
AB  - The effect of inoculum form, i.e. ungerminated conidia, germinated conidia and
      hyphae on the in vitro antifungal susceptibility of 12 strains belonging to
      Aspergillus spp. was compared using a broth microdilution method. The isolates
      were tested three times on different days against amphotericin B, itraconazole
      and ketoconazole. There were no significant differences between MICs obtained
      with the three types of inoculum (P > 0.05) for any antifungal tested. The degree
      of reproducibility of the tests was high (>or=75%) for all antifungals with each
      type of inoculum, except for itraconazole (58.3%) when the inoculum was prepared
      with ungerminated conidia.

PMID- 11328794
TI  - Ureidopenicillins and risk of Clostridium difficile infection.

PMID- 11328795
TI  - Termination of development of D0870.

PMID- 11328796
TI  - Pharmacokinetics of antibiotics in burns patients.

PMID- 11328797
TI  - In vitro inactivation of Chlamydia trachomatis and of a panel of DNA (HSV-2, CMV,
      adenovirus, BK virus) and RNA (RSV, enterovirus) viruses by the spermicide
      benzalkonium chloride.

PMID- 11328798
TI  - In vitro activity of sitafloxacin against Clostridium difficile.

PMID- 11328799
TI  - In vitro anti-methicillin-resistant Staphylococcus aureus activity of 2,4
      diacetylphloroglucinol produced by Pseudomonas sp. AMSN isolated from a marine
      alga.

PMID- 11328800
TI  - In vitro activity of co-amoxiclav acid against clinical isolates of Escherichia
      coli.

PMID- 11328801
TI  - Distribution of mef(A) and erm(B) genes in macrolide-resistant blood isolates of
      viridans group streptococci.

PMID- 11328802
TI  - Extended-spectrum beta-lactamases in blood culture isolates of Klebsiella
      pneumoniae: seek and you may find!

PMID- 11328803
TI  - Tissue penetration of a single dose of levofloxacin intravenously for antibiotic
      prophylaxis in lung surgery.

PMID- 11328804
TI  - Restoring proper radical generation by azide binding to the iron site of the
      E238A mutant R2 protein of ribonucleotide reductase from Escherichia coli.
AB  - The enzyme activity of Escherichia coli ribonucleotide reductase requires the
      presence of a stable tyrosyl free radical and diiron center in its smaller R2
      component. The iron/radical site is formed in a reconstitution reaction between
      ferrous iron and molecular oxygen in the protein. The reaction is known to
      proceed via a paramagnetic intermediate X, formally a Fe(III)-Fe(IV) state. We
      have used 9.6 GHz and 285 GHz EPR to investigate intermediates in the
      reconstitution reaction in the iron ligand mutant R2 E238A with or without azide,
      formate, or acetate present. Paramagnetic intermediates, i.e. a long-living X
      like intermediate and a transient tyrosyl radical, were observed only with azide
      and under none of the other conditions. A crystal structure of the mutant protein
      R2 E238A/Y122F with a diferrous iron site complexed with azide was determined.
      Azide was found to be a bridging ligand and the absent Glu-238 ligand was
      compensated for by azide and an extra coordination from Glu-204. A general scheme
      for the reconstitution reaction is presented based on EPR and structure results.
      This indicates that tyrosyl radical generation requires a specific ligand
      coordination with 4-coordinate Fe1 and 6-coordinate Fe2 after oxygen binding to
      the diferrous site.

PMID- 11328805
TI  - Tiam1 overexpression potentiates heregulin-induced lymphoid enhancer factor
      1/beta -catenin nuclear signaling in breast cancer cells by modulating the
      intercellular stability.
AB  - Heregulin-beta1 (HRG) promotes motility, scattering, and invasiveness of breast
      cancer cells. Tiam1, a newly identified guanine nucleotide exchange factor, has
      been shown to inhibit or promote cell migration in a cell type-dependent manner.
      In this study, we identified Tiam1 as a target of HRG signaling. HRG stimulation
      of breast cancer epithelial cells induced the phosphorylation and redistribution
      of Tiam1 to the membrane ruffles and the loosening of intercellular junctions. In
      addition, HRG-mediated scattering of breast epithelial cells was accompanied by
      stimulation of tyrosine phosphorylation and redistribution of beta-catenin from
      the cell junctions to the cytosol and, finally, entry into the nucleus.
      Decompaction of breast cancer epithelial cells by HRG was accompanied by a
      transient physical association of the tyrosine-phosphorylated beta-catenin with
      the activated human epidermal growth factor receptor 2 and subsequent nuclear
      translocation of beta-catenin, as well as beta-catenin-dependent transactivation
      of T-cell factor.lymphoid enhancer factor-1. All of these HRG-induced phenotypic
      changes were regulated in a phosphatidylinositol-3 kinase-sensitive manner. HRG
      induced cellular ruffles, loss of intercellular adhesiveness, and increased cell
      migration could be mimicked by overexpression of a fully functional Tiam1
      construct. Furthermore, ectopic expression of Tiam1 or of an active beta-catenin
      mutant led to potentiation of the beta-catenin-dependent T-cell factor.lymphoid
      enhancer factor-1 transactivation and invasiveness of HRG-treated cells. We also
      found preliminary evidence suggesting a close correlation between the status of
      Tiam1 expression and invasiveness of human breast tumor cells with the degree of
      progression of breast tumors. Together, these findings suggest that HRG regulate
      Tiam1 activation and lymphoid enhancer factor/beta-catenin nuclear signaling via
      phosphatidylinositol-3 kinase in breast cancer cells.

PMID- 11328806
TI  - Dopamine acutely stimulates Na+/H+ exchanger (NHE3) endocytosis via clathrin
      coated vesicles: dependence on protein kinase A-mediated NHE3 phosphorylation.
AB  - Dopamine (DA) is a key hormone in mammalian sodium homeostasis. DA induces
      natriuresis via acute inhibition of the renal proximal tubule apical membrane
      Na(+)/H(+) exchanger NHE3. We examined the mechanism by which DA inhibits NHE3 in
      a renal cell line. DA acutely decreases surface NHE3 antigen in dose- and time
      dependent fashion without altering total cellular NHE3. Although DA(1) receptor
      agonist alone decreases surface NHE3, simultaneous DA(2) agonist synergistically
      enhances the effect of DA(1). Decreased surface NHE3 antigen, caused by
      stimulation of NHE3 endocytosis, is dependent on intact functioning of the GTPase
      dynamin and involves increased binding of NHE3 to the adaptor protein AP2. DA
      stimulated NHE3 endocytosis can be blocked by pharmacologic or genetic protein
      kinase A inhibition or by mutation of two protein kinase A target serines (Ser
      560 and Ser-613) on NHE3. We conclude that one mechanism by which DA induces
      natriuresis is via protein kinase A-mediated phosphorylation of proximal tubule
      NHE3 leading to endocytosis of NHE3 via clathrin-coated vesicles.

PMID- 11328807
TI  - Mechanisms of cold-induced platelet actin assembly.
AB  - Various agonists but also chilling cause blood platelets to increase cytosolic
      calcium, polymerize actin, and change shape. We report that cold increases barbed
      end nucleation sites in octyl glucoside-permeabilized platelets by 3-fold,
      enabling analysis of the intermediates of this response. Although chilling does
      not change polyphosphoinositide (ppI) levels, a ppI-binding peptide completely
      inhibits cold-induced nucleation. The C terminus of N-WASp, which inhibits the
      Arp2/3 complex, blocks nucleation by 40%; GDPbetaS, N17Rac and N17Cdc42 have no
      effects. Some gelsolin translocates to the detergent-insoluble cytoskeleton after
      cooling. Chilled platelets from gelsolin-deficient mice have approximately 50%
      fewer new actin nuclei compared with platelets from wild-type mice. EGTA
      completely inhibits gelsolin translocation into the cytoskeleton, and the small
      amount of gelsolin initially there becomes soluble. Chilling releases adducin
      from the detergent-resistant cytoskeleton. We conclude that platelet actin
      filament assembly induced by cooling involves ppI-mediated actin filament barbed
      end uncapping and de novo nucleation independently of surface receptors or
      downstream signaling intermediates besides calcium. The actin-related changes
      occur in platelets at temperatures below 37 degrees C, suggesting that the
      platelet may be more activable at temperatures at the body surface than at core
      temperature, thereby favoring superficial hemostasis over internal thrombosis.

PMID- 11328808
TI  - F-actin-like ATPase activity in a polymerization-defective mutant yeast actin
      (V266G/L267G).
AB  - Polymerization increases a low level G-actin ATPase activity yielding ADP-P(i) F
      actin and then ADP F-actin following release of P(i). By monitoring P(i) release,
      we explored the relationship between the ATPase activity and polymerization
      characteristics of a mutant yeast actin, GG. In this mutant, two hydrophobic
      residues at the tip of a proposed hydrophobic plug between actin subdomains 3 and
      4, Val(266) and Leu(267), were mutated to Gly. Although GG-actin does not
      polymerize by itself in vitro, GG cells are viable. We show that GG-actin ATPase
      activity increases under normal polymerization conditions, although stable
      filaments do not form. A plot of P(i) release rate versus actin concentration
      yields an apparent critical concentration, like that seen for actin
      polymerization, of approximately 8 microm for Mg(2+) GG-actin and 11 microm for
      Ca(2+) GG-actin. In contrast to WT-actin, P(i) release from GG-actin is cold
      sensitive, reflecting the temperature sensitivity associated with mutations that
      decrease hydrophobicity in this region. Thus, under polymerization conditions, GG
      actin exhibits a continuous F-actin-like ATPase activity resulting from the
      temperature-sensitive formation of unstable cycling F-actin oligomers.
      Tropomyosin limits the extent and rate of this activity and restores
      polymerization by capturing and stabilizing these oligomers rather than enhancing
      filament nucleation.

PMID- 11328809
TI  - Crystal structure of the mitotic spindle kinesin Eg5 reveals a novel conformation
      of the neck-linker.
AB  - Success of mitosis depends upon the coordinated and regulated activity of many
      cellular factors, including kinesin motor proteins, which are required for the
      assembly and function of the mitotic spindle. Eg5 is a kinesin implicated in the
      formation of the bipolar spindle and its movement prior to and during anaphase.
      We have determined the crystal structure of the Eg5 motor domain with ADP-Mg
      bound. This structure revealed a new intramolecular binding site of the neck
      linker. In other kinesins, the neck-linker has been shown to be a critical
      mechanical element for force generation. The neck-linker of conventional kinesin
      is believed to undergo an ordered-to-disordered transition as it translocates
      along a microtubule. The structure of Eg5 showed an ordered neck-linker
      conformation in a position never observed previously. The docking of the neck
      linker relies upon residues conserved only in the Eg5 subfamily of kinesin
      motors. Based on this new information, we suggest that the neck-linker of Eg5 may
      undergo an ordered-to-ordered transition during force production. This ratchet
      like mechanism is consistent with the biological activity of Eg5.

PMID- 11328810
TI  - Cytochrome P450 CYP2J9, a new mouse arachidonic acid omega-1 hydroxylase
      predominantly expressed in brain.
AB  - A cDNA encoding a new cytochrome P450 was isolated from a mouse brain library.
      Sequence analysis reveals that this 1,958-base pair cDNA encodes a 57-58-kDa 502
      amino acid polypeptide that is 70-91% identical to CYP2J subfamily P450s and is
      designated CYP2J9. Recombinant CYP2J9 was co-expressed with NADPH-cytochrome P450
      oxidoreductase (CYPOR) in Sf9 cells using a baculovirus system. Microsomes of
      CYP2J9/CYPOR-transfected cells metabolize arachidonic acid to 19
      hydroxyeicosatetraenoic acid (HETE) thus CYP2J9 is enzymologically distinct from
      other P450s. Northern analysis reveals that CYP2J9 transcripts are present at
      high levels in mouse brain. Mouse brain microsomes biosynthesize 19-HETE. RNA
      polymerase chain reaction analysis demonstrates that CYP2J9 mRNAs are widely
      distributed in brain and most abundant in the cerebellum. Immunoblotting using an
      antibody raised against human CYP2J2 that cross-reacts with CYP2J9 detects a 56
      kDa protein band that is expressed in cerebellum and other brain segments and is
      regulated during postnatal development. In situ hybridization of mouse brain
      sections with a CYP2J9-specific riboprobe and immunohistochemical staining with
      the anti-human CYP2J2 IgG reveals abundant CYP2J9 mRNA and protein in cerebellar
      Purkinje cells. Importantly, 19-HETE inhibits the activity of recombinant P/Q
      type Ca(2+) channels that are known to be expressed preferentially in cerebellar
      Purkinje cells and are involved in triggering neurotransmitter release. Based on
      these data, we conclude that CYP2J9 is a developmentally regulated P450 that is
      abundant in brain, localized to cerebellar Purkinje cells, and active in the
      biosynthesis of 19-HETE, an eicosanoid that inhibits activity of P/Q-type Ca(2+)
      channels. We postulate that CYP2J9 arachidonic acid products play important
      functional roles in the brain.

PMID- 11328811
TI  - Hyperpolarization-activated cyclic nucleotide-gated channel 1 is a molecular
      determinant of the cardiac pacemaker current I(f).
AB  - The pacemaker current I(f) of the sinoatrial node (SAN) is a major determinant of
      cardiac diastolic depolarization and plays a key role in controlling heart rate
      and its modulation by neurotransmitters. Substantial expression of two different
      mRNAs (HCN4, HCN1) of the family of pacemaker channels (HCN) is found in rabbit
      SAN, suggesting that the native channels may be formed by different isoforms.
      Here we report the cloning and heterologous expression of HCN1 from rabbit SAN
      and its specific localization in pacemaker myocytes. rbHCN1 is an 822-amino acid
      protein that, in human embryonic kidney 293 cells, displayed electrophysiological
      properties similar to those of I(f), suggesting that HCN1 can form a pacemaker
      channel. The presence of HCN1 in the SAN myocytes but not in nearby heart
      regions, and the electrophysiological properties of the channels formed by it,
      suggest that HCN1 plays a central and specific role in the formation of SAN
      pacemaker currents.

PMID- 11328812
TI  - Protein kinases C translocation responses to low concentrations of arachidonic
      acid.
AB  - Arachidonic acid (AA) directly activates protein kinases C (PKC) and may thereby
      serve as a regulatory signal during cell stimulation. The effect, however,
      requires a > or =20 microm concentration of the fatty acid. We find that human
      polymorphonuclear neutrophils (PMN) equilibrated with a ligand for the
      diacylglycerol receptor on PKC, [(3)H]phorbol dibutyrate (PDB), increased binding
      of [(3)H]PDB within 15 s of exposure to > or =10-30 nm AA. Other unsaturated
      fatty acids, but not a saturated fatty acid, likewise stimulated PDB binding.
      These responses, similar to those caused by chemotactic factors, resulted from a
      rise in the number of diacylglycerol receptors that were plasma membrane
      associated and therefore accessible to PDB. Unlike chemotactic factors, however,
      AA was fully active on cells overloaded with Ca(2+) chelators. The major
      metabolites of AA made by PMN, leukotriene B(4) and 5-hydroxyicosatetraenoate,
      did not mimic AA, and an AA antimetabolite did not block responses to AA. AA also
      induced PMN to translocate cytosolic PKCalpha, beta(II), and delta to membranes.
      This response paralleled PDB binding with respect to dose requirements, time,
      Ca(2+)-independence, resistance to an AA antimetabolite, and induction by another
      unsaturated fatty acid but not by a saturated fatty acid. Finally, HEK 293 cells
      transfected with vectors encoding PKCbeta(I) or PKCdelta fused to the reporter
      enhanced green fluorescent protein (EGFP) were studied. AA caused EGFP-PKCbeta
      translocation from cytosol to plasma membrane at > or =0.5 microm, and EGFP
      PKCdelta translocation from cytosol to nuclear and, to a lesser extent, plasma
      membrane at as little as 30 nm. We conclude that AA induces PKC translocations to
      specific membrane targets at concentrations 2-4 orders of magnitude below those
      activating the enzymes. These responses, at least as they occur in PMN, do not
      require changes in cell Ca(2+) or oxygenation of the fatty acid. AA seems more
      suited for signaling the movement than activation of PKC.

PMID- 11328813
TI  - Insights into the molecular mechanism of mitochondrial toxicity by AIDS drugs.
AB  - Several of the nucleoside analogs used in the treatment of AIDS exhibit a delayed
      clinical toxicity limiting their usefulness. The toxicity of nucleoside analogs
      may be related to their effects on the human mitochondrial DNA polymerase (Pol
      gamma), the polymerase responsible for mitochondrial DNA replication. Among the
      AIDS drugs approved by the FDA for clinical use, two are modified cytosine
      analogs, Zalcitabine (2',3'-dideoxycytidine (ddC)) and Lamivudine (beta-d-(+)
      2',3'-dideoxy-3'-thiacytidine ((-)3TC])). (-)3TC is the only analog containing an
      unnatural l(-) nucleoside configuration and is well tolerated by patients even
      after long term administration. In cell culture (-)3TC is less toxic than its
      d(+) isomer, (+)3TC, containing the natural nucleoside configuration, and both
      are considerably less toxic than ddC. We have investigated the mechanistic basis
      for the differential toxicity of these three cytosine analogs by comparing the
      effects of dideoxy-CTP), (+)3TC-triphosphate (TP), and (-)3TC-TP on the
      polymerase and exonuclease activities of recombinant human Pol gamma. This
      analysis reveals that Pol gamma incorporates (-)3TC-triphosphate 16-fold less
      efficiently than the corresponding (+)isomer and 1140-fold less efficiently than
      dideoxy-CTP, showing a good correlation between incorporation rate and toxicity.
      The rates of excision of the incorporated analogs from the chain-terminated 3'
      end of the DNA primer by the 3'-5'-exonuclease activity of Pol gamma were similar
      (0.01 s(-)1) for both 3TC analogs. In marked contrast, the rate of exonuclease
      removal of a ddC chain-terminated DNA occurs at least 2 orders of magnitude
      slower, suggesting that the failure of the exonuclease to remove ddC may play a
      major role in its greater toxicity. This study demonstrates that direct analysis
      of the mitochondrial DNA polymerase structure/function relationships may provide
      valuable insights leading to the design of less toxic inhibitors.

PMID- 11328814
TI  - Effects of protein kinase CK2, extracellular signal-regulated kinase 2, and
      protein phosphatase 2A on a phosphatidic acid-preferring phospholipase A1.
AB  - A soluble, phosphatidic acid-preferring phospholipase A1, expressed in mature
      bovine testes but not in newborn calf testes, may contribute to the formation or
      function of sperm. Here we incubated a recombinant preparation of the
      phospholipase in vitro with several enzymes including protein kinase CK2 (CK2),
      extracellular signal-regulated kinase 2 (ERK2), and protein phosphatase 2A (PP2A)
      to identify effects that might be of regulatory importance in vivo. Major
      findings were that 1) CK2 phosphorylated the phospholipase on serines 93, 105,
      and 716; 2) ERK2 phosphorylated the enzyme on serine 730; 3) there was cross
      antagonism between the reactions that phosphorylated serines 716 and 730; 4) PP2A
      selectively hydrolyzed phosphate groups that were esterified to serines 716 and
      730; 5) CK2alpha formed a stable, MgATP/MgGTP-dependent complex with the
      phospholipase by a novel mechanism; and 6) the complex showed reduced
      phospholipase activity and resembled a complex identified in homogenates of
      macaque testis. These results provide the first available information about the
      effects of reactions of phosphorylation and dephosphorylation on the behavior of
      the phospholipase, shed light on properties of CK2alpha that may be required for
      the formation of complexes with its substrates, and raise the possibility that a
      complex containing CK2alpha and the phospholipase may play a special biological
      role in the testis.

PMID- 11328815
TI  - Structure of the pore-forming transmembrane domain of a ligand-gated ion channel.
AB  - The structure of the pore-forming transmembrane domain of the nicotinic
      acetylcholine receptor from Torpedo has been investigated by infrared
      spectroscopy. Treatment of affinity-purified receptor with either Pronase or
      proteinase K digests the extramembranous domains (roughly 75% of the protein
      mass), leaving hydrophobic membrane-imbedded peptides 3-6 kDa in size that are
      resistant to peptide (1)H/(2)H exchange. Infrared spectra of the transmembrane
      domain preparations exhibit relatively sharp and symmetric amide I and amide II
      band contours centered near 1655 and 1545 cm(-)1, respectively, in both (1)H(2)O
      and (2)H(2)O. The amide I band is very similar to the amide I bands observed in
      the spectra of alpha-helical proteins, such as myoglobin and bacteriorhodopsin,
      that lack beta structure and exhibit much less beta-sheet character than is
      observed in proteins with as little as 20% beta sheet. Curve-fitting estimates 75
      80% alpha-helical character, with the remaining peptides likely adopting extended
      and/or turn structures at the bilayer surface. Infrared dichroism spectra are
      consistent with transmembrane alpha-helices oriented perpendicular to the bilayer
      surface. The evidence strongly suggests that the transmembrane domain of the
      nicotinic receptor, the most intensively studied ligand-gated ion channel, is
      composed of five bundles of four transmembrane alpha-helices.

PMID- 11328816
TI  - Purification, characterization, molecular cloning, and subcellular distribution
      of neutral ceramidase of rat kidney.
AB  - Previously, we reported two types of neutral ceramidase in mice, one solubilized
      by freeze-thawing and one not. The former was purified as a 94-kDa protein from
      mouse liver, and cloned (Tani, M., Okino, N., Mori, K., Tanigawa, T., Izu, H.,
      and Ito, M. (2000) J. Biol. Chem. 275, 11229--11234). In this paper, we describe
      the purification, molecular cloning, and subcellular distribution of a 112-kDa
      membrane-bound neutral ceramidase of rat kidney, which was completely insoluble
      by freeze-thawing. The open reading frame of the enzyme encoded a polypeptide of
      761 amino acids having nine putative N-glycosylation sites and one possible
      transmembrane domain. In the ceramidase overexpressing HEK293 cells, 133-kDa
      (Golgi-form) and 113-kDa (endoplasmic reticulum-form) Myc-tagged ceramidases were
      detected, whereas these two proteins were converted to a 87-kDa protein
      concomitantly with loss of activity when expressed in the presence of
      tunicamycin, indicating that the N-glycosylation process is indispensable for the
      expression of the enzyme activity. Immunohistochemical analysis clearly showed
      that the ceramidase was mainly localized at the apical membrane of proximal
      tubules, distal tubules, and collecting ducts in rat kidney, while in liver the
      enzyme was distributed with endosome-like organelles in hepatocytes.
      Interestingly, the kidney ceramidase was found to be enriched in the raft
      microdomains with cholesterol and GM1 ganglioside.

PMID- 11328817
TI  - Evi-1 transforming and repressor activities are mediated by CtBP co-repressor
      proteins.
AB  - Ectopic production of the EVI1 transcriptional repressor zinc finger protein is
      seen in 4--6% of human acute myeloid leukemias. Overexpression also transforms
      Rat1 fibroblasts by an unknown mechanism, which is likely to be related to its
      role in leukemia and which depends upon its repressor activity. We show here that
      mutant murine Evi-1 proteins, lacking either the N-terminal zinc finger DNA
      binding domain or both DNA binding zinc finger clusters, function as dominant
      negative mutants by reverting the transformed phenotype of Evi-1 transformed Rat1
      fibroblasts. The dominant negative activity of the non-DNA binding mutants
      suggests sequestration of transformation-specific cofactors and that recruitment
      of these cellular factors might mediate Evi-1 transforming activity. C-terminal
      binding protein (CtBP) co-repressor family proteins bind PLDLS-like motifs. We
      show that the murine Evi-1 repressor domain has two such sites, PFDLT (site a,
      amino acids 553--559) and PLDLS (site b, amino acids 584--590), which
      independently can bind CtBP family co-repressor proteins, with site b binding
      with higher affinity than site a. Functional analysis of specific CtBP binding
      mutants show site b is absolutely required to mediate both transformation of Rat1
      fibroblasts and transcriptional repressor activity. This is the first
      demonstration that the biological activity of a mammalian cellular
      transcriptional repressor protein is mediated by CtBPs. Furthermore, it suggests
      that CtBP proteins are involved in the development of some acute leukemias and
      that blocking their ability to specifically interact with EVI1 might provide a
      target for the development of pharmacological therapeutic agents.

PMID- 11328818
TI  - Identification and characterization of S2V, a novel putative siglec that contains
      two V set Ig-like domains and recruits protein-tyrosine phosphatases SHPs.
AB  - We describe the molecular cloning and characterization of S2V, a novel sialic
      acid binding immunoglobulin-like lectin. The cDNA of S2V encodes a type 1
      transmembrane protein with four extracellular immunoglobulin-like (Ig-like)
      domains and a cytoplasmic tail bearing a typical immunoreceptor tyrosine-based
      inhibitory motif (ITIM) and an ITIM-like motif. A unique feature of S2V is the
      presence of two V-set Ig-like domains responsible for the binding to sialic acid,
      whereas all other known siglecs possess only one. S2V is predominantly expressed
      in macrophage. In vivo S2V was tyrosine-phosphorylated when co-expressed with
      exogenous c-Src kinase. Upon tyrosine phosphorylation, S2V recruits both Src
      homology 2 (SH2) domain-containing protein-tyrosine phosphatases SHP-1 and SHP-2,
      two important inhibitory regulators of immunoreceptor signal transduction. These
      findings suggest that S2V is involved in the negative regulation of the signaling
      in macrophage by functioning as an inhibitory receptor. When expressed in COS-7
      cells, S2V was able to mediate sialic acid-dependent binding to human red blood
      cells, suggesting that S2V may function through cell-cell interaction.

PMID- 11328819
TI  - Ribozyme targeting demonstrates that the nuclear receptor coactivator AIB1 is a
      rate-limiting factor for estrogen-dependent growth of human MCF-7 breast cancer
      cells.
AB  - Human breast tumorigenesis is promoted by the estrogen receptor pathway, and
      nuclear receptor coactivators are thought to participate in this process. Here we
      studied whether one of these coactivators, AIB1 (amplified in breast cancer 1),
      was rate-limiting for hormone-dependent growth of human MCF-7 breast cancer
      cells. We developed MCF-7 breast cancer cell lines in which the expression of
      AIB1 can be modulated by regulatable ribozymes directed against AIB1 mRNA. We
      found that depletion of endogenous AIB1 levels reduced steroid hormone signaling
      via the estrogen receptor alpha or progesterone receptor beta on transiently
      transfected reporter templates. Down-regulation of AIB1 levels in MCF-7 cells did
      not affect estrogen-stimulated cell cycle progression but reduced estrogen
      mediated inhibition of apoptosis and cell growth. Finally, upon reduction of
      endogenous AIB1 expression, estrogen-dependent colony formation in soft agar and
      tumor growth of MCF-7 cells in nude mice was decreased. From these findings we
      conclude that, despite the presence of different estrogen receptor coactivators
      in breast cancer cells, AIB1 exerts a rate-limiting role for hormone-dependent
      human breast tumor growth.

PMID- 11328820
TI  - Superinhibition of sarcoplasmic reticulum function by phospholamban induces
      cardiac contractile failure.
AB  - To determine whether selective impairment of cardiac sarcoplasmic reticulum (SR)
      Ca(2+) transport may drive the progressive functional deterioration leading to
      heart failure, transgenic mice, overexpressing a phospholamban Val(49) --> Gly
      mutant (2-fold), which is a superinhibitor of SR Ca(2+)-ATPase affinity for
      Ca(2+), were generated, and their cardiac phenotype was examined longitudinally.
      At 3 months of age, the increased EC(50) level of SR Ca(2+) uptake for Ca(2+)
      (0.67 +/- 0.09 microm) resulted in significantly higher depression of
      cardiomyocyte rates of shortening (57%), relengthening (31%), and prolongation of
      the Ca(2+) signal decay time (165%) than overexpression (2-fold) of wild type
      phospholamban (68%, 64%, and 125%, respectively), compared with controls (100%).
      Echocardiography also revealed significantly depressed function and impaired beta
      adrenergic responses in mutant hearts. The depressed contractile parameters were
      associated with left ventricular remodeling, recapitulation of fetal gene
      expression, and hypertrophy, which progressed to dilated cardiomyopathy with
      interstitial tissue fibrosis and death by 6 months in males. Females also had
      ventricular hypertrophy at 3 months but exhibited normal systolic function up to
      12 months of age. These results suggest a causal relationship between defective
      SR Ca(2+) cycling and cardiac remodeling leading to heart failure, with a gender
      dependent influence on the time course of these alterations.

PMID- 11328821
TI  - The N-terminal region of human progesterone B-receptors: biophysical and
      biochemical comparison to A-receptors.
AB  - To understand the basis for functional differences between the two human
      progesterone receptors (PR), we have carried out a detailed biochemical and
      biophysical analysis of the N-terminal region of each isoform. Extending our
      previous work on the A-isoform (Bain, D. L, Franden, M. A., McManaman, J. L.,
      Takimoto, G. S., and Horwitz, K. B. (2000) J. Biol. Chem. 275, 7313-7320), here
      we present studies on the N-terminal region of the B-isoform (NT-B) and compare
      its properties to its A-receptor counterpart (NT-A). As seen previously with NT
      A, NT-B is quantitatively monomeric in solution, yet undergoes N-terminal
      mediated assembly upon DNA binding. Limited proteolysis, microsequencing, and
      sedimentation analyses indicate that the B-isoform exists in a non-globular,
      extended conformation very similar to that of NT-A. Additionally, the 164 amino
      acids unique to the B-isoform (BUS) appear to be in a more extended conformation
      relative to sequences common to both receptors and do not exist as an independent
      structural domain. However, sedimentation studies of NT-A and NT-B show
      differences in the ensemble distribution of their conformational states. We
      hypothesize that isoform-specific functional differences are not due to
      structural differences, per se. Rather, the transcriptional element BUS, or
      possibly other transcription factors, causes a redistribution of the
      conformational ensemble by stabilizing a more functionally active set of
      conformations in NT-B.

PMID- 11328822
TI  - Crystal structure of the dimeric C-terminal domain of TonB reveals a novel fold.
AB  - The TonB-dependent complex of Gram-negative bacteria couples the inner membrane
      proton motive force to the active transport of iron.siderophore and vitamin B(12)
      across the outer membrane. The structural basis of that process has not been
      described so far in full detail. The crystal structure of the C-terminal domain
      of TonB from Escherichia coli has now been solved by multiwavelength anomalous
      diffraction and refined at 1.55-A resolution, providing the first evidence that
      this region of TonB (residues 164-239) dimerizes. Moreover, the structure shows a
      novel architecture that has no structural homologs among any known proteins. The
      dimer of the C-terminal domain of TonB is cylinder-shaped with a length of 65 A
      and a diameter of 25 A. Each monomer contains three beta strands and a single
      alpha helix. The two monomers are intertwined with each other, and all six beta
      strands of the dimer make a large antiparallel beta-sheet. We propose a plausible
      model of binding of TonB to FhuA and FepA, two TonB-dependent outer-membrane
      receptors.

PMID- 11328823
TI  - HIV-1 Nef promotes survival of myeloid cells by a Stat3-dependent pathway.
AB  - Human immunodeficiency virus Nef is a small myristylated protein that plays a
      critical role in AIDS progression. Nef binds with high affinity to the SH3 domain
      of the myeloid-restricted tyrosine kinase Hck in vitro, identifying this Src
      related kinase as a possible cellular target for Nef in macrophages. Here we show
      that Nef activates endogenous Hck in the granulocyte-macrophage colony
      stimulating factor-dependent myeloid cell line, TF-1. Unexpectedly, Nef induced
      cytokine-independent TF-1 cell outgrowth and constitutive activation of the Stat3
      transcription factor. Induction of survival required the Nef SH3 binding and
      membrane-targeting motifs and was blocked by dominant-negative Stat3 mutants. Nef
      also stimulated Stat3 activation in primary human macrophages, providing evidence
      for Stat3 as a Nef effector in a target cell for human immunodeficiency virus.

PMID- 11328824
TI  - Involvement of the activation loop of ERK in the detachment from cytosolic
      anchoring.
AB  - The Extracellular signal-regulated kinases (ERKs) are translocated into the
      nucleus in response to mitogenic stimulation. The mechanism of translocation and
      the residues in ERKs that govern this process are not clear as yet. Here we
      studied the involvement of residues in the activation loop of ERK2 in determining
      its subcellular localization. Substitution of residues in the activation loop to
      alanines indicated that residues 173-181 do not play a significant role in the
      phosphorylation and activation of ERK2. However, residues 176-181 are responsible
      for the detachment of ERK2 from MEK1 upon mitogenic stimulation. This
      dissociation can be mimicked by substitution of residues 176-178 to alanines and
      is prevented by deletion of these residues or by substitution of residues 179-181
      to alanines. On the other hand, residues 176-181, as well as residues essential
      for ERK2 dimerization, do not play a role in the shuttle of ERK2 through nuclear
      pores. Thus, phosphorylation-induced conformational rearrangement of residues in
      the activation loop of ERK2 plays a major role in the control of subcellular
      localization of this protein.

PMID- 11328825
TI  - Transgenic targeting of a dominant negative corepressor to liver blocks basal
      repression by thyroid hormone receptor and increases cell proliferation.
AB  - Unliganded thyroid hormone receptors (TRs) interact with corepressors and repress
      basal transcription of target genes in cotransfection and in vitro studies.
      Currently, little is known about the function of corepressors in vivo. We thus
      used a mouse albumin promoter to generate several transgenic mouse lines that
      overexpressed a dominant negative mutant corepressor, NCoRi, in liver. The
      transgenic mice had normal liver weight, appearance, and minimal changes in
      enzyme activity. To study the effects of NCoRi on transcription of hepatic target
      genes, we examined T3-regulated gene expression of hypo- and hyperthyroid
      transgenic mice. In hypothyroid mice, hepatic expression of Spot 14, Bcl-3,
      glucose 6-phosphatase, and 5'-deiodinase mRNA was higher in transgenic mice than
      littermate controls whereas these genes were induced to similar levels in T3
      treated mice. Derepression was not observed for malic enzyme mRNA expression in
      hypothyroid mice. Thus, NCoRi selectively blocked basal transcription of several
      thyroid hormone-responsive genes but had no effect on ligand-mediated
      transcription. Additionally, compensatory increases in endogenous SMRT and NCoR
      mRNA were observed in hypothyroid transgenic mice. Interestingly, hepatocyte
      proliferation as detected by BrdUrd incorporation was increased in transgenic
      mice. The gene profile in transgenic mouse livers was studied by cDNA microarray,
      and several genes related to cell proliferation were induced. In summary, our
      studies show that NCoR plays important roles in mediating basal repression by TRs
      and may prevent cellular proliferation in vivo.

PMID- 11328826
TI  - ATP-binding cassette transporter A1 contains an NH2-terminal signal anchor
      sequence that translocates the protein's first hydrophilic domain to the
      exoplasmic space.
AB  - Mutations in the ATP-binding cassette transporter A1 (ABCA1) transporter are
      associated with Tangier disease and a defect in cellular cholesterol efflux. The
      amino terminus of the ABCA1 transporter has two putative in-frame translation
      initiation sites, 60 amino acids apart. A cluster of hydrophobic amino acids form
      a potentially cleavable signal sequence in this 60-residue extension. We
      investigated the functional role of this extension and found that it was required
      for stable protein expression of transporter constructs containing any downstream
      transmembrane domains. The extension directed transporter translocation across
      the ER membrane with an orientation that resulted in glycosylation of amino acids
      immediately distal to the signal sequence. Neither the native signal sequence nor
      a green fluorescent protein tag, fused at the amino terminus, was cleaved from
      ABCA1. The green fluorescent protein fusion protein had efflux activity
      comparable with wild type ABCA1 and demonstrated a predominantly plasma membrane
      distribution in transfected cells. These data establish a requirement for the
      upstream 60 amino acids of ABCA1. This region contains an uncleaved signal anchor
      sequence that positions the amino terminus in a type II orientation leading to
      the extracellular presentation of an approximately 600-amino acid loop in which
      loss-of-function mutations cluster in Tangier disease patients.

PMID- 11328829
TI  - IgA deficiency: what we should-or should not-be doing.

PMID- 11328830
TI  - Measurement of total antioxidant capacity.

PMID- 11328831
TI  - Autoantibodies and overlap syndromes in autoimmune rheumatic disease.
AB  - Many patients diagnosed with autoimmune rheumatic disease cannot be categorised
      easily into one of the established clinical entities such as systemic lupus
      erythematosus, dermatomyositis, or systemic sclerosis. The term "overlap
      syndrome" has been increasingly used to identify such patients and is useful in
      terms of clarifying prognosis and facilitating disease management. This article
      reviews overlap syndrome in autoimmune rheumatic disease, with particular
      emphasis on the associated serological markers.

PMID- 11328832
TI  - Interpreting bruises at necropsy.
AB  - The accurate interpretation of bruising at necropsy is essential to understanding
      how a victim has been injured and assists the pathologist in a reliable
      reconstruction of the events leading to death. It is essential not only to assess
      the mechanism of production of a bruise, taking into account the type of
      impacting surface and the magnitude of force used, but also to estimate when the
      injury was caused. An account is given of the various methods used in the
      examination of bruises, particularly with respect to aging, as well as the
      factors that may affect their appearance. Differentiation from artefacts
      resulting from postmortem changes is also discussed in some detail.

PMID- 11328834
TI  - Rapid identification of candida species by TaqMan PCR.
AB  - AIM: To develop and evaluate a TaqMan(TM) polymerase chain reaction (PCR) for the
      rapid identification and speciation of candida species. METHODS: Species specific
      primer and probe sets were designed for the identification of Candida albicans,
      C. parapsilosis, C. tropicalis, C. krusei, C. kefyr, and C. glabrata from
      clinical isolates in a 5' exonuclease (TaqMan(TM)) assay. The probes were
      labelled with three fluorescent dyes to enable differentiation between species
      when three primer and probe sets were combined in two multiplexes. The
      specificity of these assays was evaluated against a range of National Collection
      of Pathogenic Fungi strains, clinical isolates of yeast, bacterial and viral
      pathogens. RESULTS: The primer and probe sets have been shown to be 100% specific
      for their respective species; there was no crossreaction between any set and
      human DNA, or extracts from other candida species, fungal, bacterial, or viral
      pathogens tested. Extracts from two clinical isolates, originally identified as C
      albicans on the basis of germ tube formation, were not amplified by any of the
      primer and probe sets. These isolates have been putatively re-identified as C
      dubliniensis after sequencing of the variable internal transcribed spacer region
      ITS2 and lack of growth at 45 degrees C. CONCLUSION: This TaqMan assay provides a
      rapid alternative to conventional culture based techniques for the identification
      and speciation of the most frequently isolated candida species. The simple
      extraction method followed by TaqMan PCR can identify the six species mentioned
      in four hours.

PMID- 11328833
TI  - Method for the measurement of antioxidant activity in human fluids.
AB  - AIM: To develop a new, simple, and cheap method for estimating antioxidant
      activity in human fluids. METHODS: The assay measured the capacity of the
      biological fluids to inhibit the production of thiobarbituric acid reactive
      substances (TBARS) from sodium benzoate under the influence of the free oxygen
      radicals derived from Fenton's reaction. A solution of 1 mmol/litre uric acid was
      used as standard. RESULTS: The following mean (SD) antioxidative activities were
      found (as uric acid) in the various biological fluids: serum, 2.04 (0.20)
      mmol/litre; urine, 176.5 (25.6) micromol/litre; cerebrospinal fluid, 95.0 (26.9)
      micromol/litre; aqueous humour oculi, 61.25 (9.9) micromol/litre; saliva, 838.5
      (48.2) micromol/litre; tears, 247.0 (17.0) micromol/litre; ascites fluid, 270.0
      (63.3) micromol/litre; kidney cyst fluid, 387.1 (28.1) micromol/litre. Small
      samples of the biological material were needed for the analyses: 10 microl of
      serum and 50-100 microl of other body fluids. In the sera of 48 healthy
      individuals there was a significant positive correlation between values obtained
      with the Randox method (as a reference method) and the new method proposed here
      (correlation coefficient, 0.8728; mean difference between methods, <0.4%).
      CONCLUSIONS: This method is easy, rapid, reliable, and practical for the routine
      measurement of total antioxidant activity in serum and other human body fluids.
      Small samples of biological material are needed for the analyses and the results
      are comparable with the reference (Randox) method.

PMID- 11328835
TI  - Comparison of precancerous conditions: atrophy and intestinal metaplasia in
      Helicobacter pylori gastritis among Chinese and Dutch patients.
AB  - AIM-Atrophy and intestinal metaplasia (IM) as precancerous conditions
      consistently begin in the antrum and are most severe along the lesser curvature.
      The aim of this study was to investigate discrepancies in the prevalence, the
      severity of atrophy, and IM in antral mucosa of Helicobacter pylori infected
      gastritis and difference in age of onset among Chinese and Dutch patients.
      METHODS-Two hundred and sixty five Chinese patients and 261 Dutch patients with H
      pylori infection were enrolled. The degrees of atrophy and IM were graded
      according to the updated Sydney system. RESULTS-The overall prevalences of
      atrophy and IM were lower in Dutch patients (42% and 26%, respectively) than in
      Chinese patients (52% and 32%, respectively). Only the difference in atrophy
      reached significance (p = 0.028). However, in both Chinese and Dutch patients,
      the degrees of atrophy and IM were low and severe degrees were rare. The mean
      ages of Chinese and Dutch patients with atrophy and IM were higher than those
      without atrophy and IM (with atrophy (Chinese patients): mean, 42.12; SD, 9.80;
      with IM (Chinese patients): mean, 42.56; SD, 9.96; with atrophy (Dutch patients):
      mean, 55.16; SD, 12.20; with IM (Dutch patients): mean, 57.79; SD, 11.13; without
      atrophy (Chinese patients): mean, 39.71; SD, 10.16; without IM (Chinese
      patients): mean, 40.19; SD, 9.99; without atrophy (Dutch patients): mean, 45.70;
      SD, 12.44; without IM (Dutch patients): mean, 46.89; SD, 12.68). Atrophy and IM
      occurred earlier and were more severe in Chinese patients, with both reaching a
      peak value in patients over 60 years. CONCLUSIONS-There are geographical
      differences in the prevalence and severity of H pylori infected gastritis, in
      particular with respect to atrophy and IM, which suggests that infection with H
      pylori occurs earlier in life and has a higher prevalence in CHINA:

PMID- 11328836
TI  - A microbiological study of Papillon-Lefevre syndrome in two patients.
AB  - AIM: To analyse the microflora of subgingival plaque from patients with Papillon
      Lefevre syndrome (PLS), which is a very rare disease characterised by palmar
      plantar hyperkeratosis with precocious periodontal destruction. METHODS:
      Bacterial isolates were identified using a combination of commercial
      identification kits, traditional laboratory tests, and gas liquid chromatography.
      Some isolates were also subjected to partial 16S rDNA sequencing. Plaque samples
      were also assayed for the presence of Porphyromonas gingivalis, Prevotella
      intermedia, and Actinobacillus actinomycetemcomitans in a quantitative enzyme
      linked immunosorbent assay (ELISA) using monoclonal antibodies. RESULTS: The
      culture results showed that most isolates were capnophilic and facultatively
      anaerobic species-mainly Capnocytophaga spp and Streptococcus spp. The latter
      included S. constellatus, S. oralis, and S. sanguis. Other facultative bacteria
      belonged to the genera gemella, kingella, leuconostoc, and stomatococcus. The
      aerobic bacteria isolated were species of neisseria and bacillus. Anaerobic
      species included Prevotella intermedia, P. melaninogenica, and P. nigrescens, as
      well as Peptostreptococcus spp. ELISA detected P gingivalis in one patient in all
      sites sampled, whereas A. actinomycetemcomitans was detected in only one site
      from the other patient. Prevotella intermedia was present in low numbers.
      CONCLUSIONS: Patients with PLS have a very complex subgingival flora including
      recognised periodontal pathogens. However, no particular periodontopathogen is
      invariably associated with PLS.

PMID- 11328837
TI  - Distribution and viral load of type specific HPVs in different cervical lesions
      as detected by PCR-ELISA.
AB  - AIMS: To investigate the distribution and viral load of the most prevalent high
      risk human papillomavirus (HPV) types 16, 18, 31, 33, and 45 and low risk HPV
      types 6 and 11 in a variety of cervical lesions. METHODS: One hundred and seventy
      six cytological specimens from women with different cervical lesions were
      investigated. For an accurate standardisation of the sample, cervical cells were
      counted and a volume of the cell suspension processed by polymerase chain
      reaction-enzyme linked immunosorbent assay (PCR-ELISA). Semiquantitative
      determinations were achieved in relation to an external reference titration
      curve. RESULTS: HPV DNA was detected in 60.2% of the samples. HPV-16 was the
      prevalent genotype (57.6%), followed by HPV-33, HPV-31, HPV-6, HPV-18, and HPV
      45. HPV-11 was not detected. HPV-16 showed a pronounced increase in prevalence
      with the evolution of cervical disease. Semiquantitative evaluation of the
      results showed that only HPV-16 DNA could reach very high values (> 1000 genome
      copies/cell) and a very high HPV-16 load correlated with the severity of cervical
      disease. CONCLUSIONS: Only HPV-16 load appears to be associated with the severity
      of cervical disease.

PMID- 11328838
TI  - Retain or sacrifice the posterior cruciate ligament in total knee arthroplasty? A
      histopathological study of the cruciate ligament in osteoarthritic and rheumatoid
      disease.
AB  - BACKGROUND: The decision whether to retain or resect the posterior cruciate
      ligament in total knee arthroplasty is at present determined clinically by
      preoperative radiological variables focusing upon the amount of joint
      destruction, and subsequent soft tissue contractures. However, these variables
      give only indirect information on the histological integrity and proprioceptive
      properties of the posterior cruciate ligament. METHODS: Twenty posterior cruciate
      ligaments, obtained during total knee arthroplasty, were evaluated histologically
      to study the relation between the degree of preoperative radiological joint
      destruction, structural integrity of the posterior cruciate ligament and the
      neurological integrity of the targeted tissue. Eleven patients had osteoarthritis
      and nine patients rheumatoid arthritis. Haematoxylin and eosin, Alcian blue
      (mucoid degeneration), elastica von Gieson, Gomori (elastic fibres and collagen),
      and immunohistochemical staining for neural structures were used. RESULTS: In all
      but one of the posterior cruciate ligaments, morphologically intact neural tissue
      was present in the peritendineum of the ligaments. Structural integrity of the
      collagen framework was present in only seven posterior cruciate ligaments. These
      cases all had grade three or four radiological joint destruction. In 13 of the
      specimens a certain degree of mucoid degeneration of collagen was present. All
      patients with grade five radiological knee joint destruction displayed mucoid
      degeneration and irregularity of the posterior cruciate ligament fibres.
      CONCLUSION: Because of the extensive architectural and probably functional damage
      of the posterior cruciate ligament in patients who have grade five radiological
      knee joint destruction, retention of the posterior cruciate ligament in knee
      prosthesis should not be advocated.

PMID- 11328839
TI  - Observer accuracy in estimating proportions in images: implications for the
      semiquantitative assessment of staining reactions and a proposal for a new
      system.
AB  - BACKGROUND: The results of immunohistochemical staining are often assessed by
      semiquantitative scoring. However, these scoring systems are usually non
      standardised and there has been little evaluation of the accuracy and reliability
      of this subjective assessment. AIMS: To assess the accuracy of observer
      estimation of proportions of objects in an image. METHODS: Images were generated
      that contained known proportions of pink squares in grids of 50 x 50 and 100 x
      100 squares. Observers were shown each image for five seconds in random order and
      either estimated the proportion of pink squares or selected the image (from a
      pair of images) that contained the greater proportion of pink squares. The
      observers were four consultant histopathologists, seven trainee
      histopathologists, and six control non-histopathologists. RESULTS: The raw
      estimations of proportions showed a close correlation with the real proportions,
      with correlation coefficients of 0.94 and 0.95 for consultant and trainee
      histopathologists on the 50 x 50 grids. However, the performance in the
      comparison task was much higher, with an almost perfect classification for grids
      of equal size even when the proportions only differed by 5%. CONCLUSIONS:
      Histopathologists can estimate proportions of objects in an image with a
      reasonable degree of accuracy in this abstract test system. All observers,
      whether histopathologists or not, can discriminate between proportions that are
      only 5% different in equal sized image grids. This suggests that the generation
      and use of carefully calibrated reference images could greatly improve the
      accuracy and reliability of semiquantitative scoring of immunohistochemical or
      any other staining.

PMID- 11328840
TI  - Reduced expression of alpha-catenin, beta-catenin, and gamma-catenin is
      associated with high cell proliferative activity and poor differentiation in non
      small cell lung cancer.
AB  - AIMS: To investigate the expression of catenins (alpha, beta, and gamma) in non
      small cell lung carcinoma (NSCLC) and its relation to clinicopathological factors
      and prognosis. METHODS: The expression of catenins was analysed
      immunohistochemically in 261 patients with resected NSCLC, diagnosed between 1978
      and 1996 in eastern Finland: The cell proliferation index of the tumours was
      analysed by means of an image analyser. The staining results were compared with
      clinicopathological characteristics and survival. RESULTS: Normal catenin
      staining was found significantly more often in adenocarcinomas than in squamous
      cell carcinomas or anaplastic/large cell carcinomas. Reduced staining of alpha
      catenin, beta-catenin, and gamma-catenin was related to poor differentiation of
      the tumour. The tumours with reduced staining of beta-catenin or gamma-catenin
      often had higher cell proliferation activity. Nuclear staining of beta-catenin
      and gamma-catenin was found in 16 (7%) and 29 (13%) cases, respectively. This
      nuclear staining correlated directly with increased cell proliferation and
      inversely with membranous staining. In survival analyses the predictors of
      overall and disease free survival were stage and tumour type. The expression of
      catenins did not affect survival. CONCLUSIONS: The expression of alpha-catenin,
      beta-catenin, and gamma-catenin is related to histological type and
      differentiation in NSCLC, although catenins have no independent prognostic value.
      However, this study supports the important role of the nuclear accumulation of
      beta-catenin and gamma-catenin in highly proliferative cells.

PMID- 11328841
TI  - An unusually aggressive case of endometriosis showing p53 expression.
AB  - A 43 year old woman who underwent a hysterectomy and bilateral salpingo
      oophorectomy for secondary dysmenorrhoea was found to have bilateral ovarian
      endometriosis. During the following four years she developed a series of tumour
      like vaginal masses, which were locally excised, a pelvic mass causing acute
      large bowel obstruction, which necessitated an emergency Hartmann's procedure,
      and a further pelvic mass causing hydronephrosis with a non-functioning kidney.
      Pathological examination of all the resected specimens showed endometriosis with
      abundant stromal and glandular elements. Immunoreactivity for p53 protein was
      detected within endometriotic foci from the initial oophorectomy as well as the
      latest resection specimens. Immunostaining for p53 may help identify potentially
      aggressive cases of endometriosis for proactive treatment.

PMID- 11328842
TI  - Florid cystic endosalpingiosis of the uterus.
AB  - A 73 year old woman presented with a right sided adnexal cystic mass. At
      laparotomy, this proved to be a benign serous ovarian cyst and an aggregation of
      thin walled subserosal and soft tissue cysts and spongy nodules up to 16 mm in
      diameter involving the side wall of the uterus and adjacent parametrium. These
      were removed by total abdominal hysterectomy and bilateral salpingo-oophorectomy.
      Histologically, the cystic spaces and smaller acini were lined by benign tubo
      endometrioid epithelium, with smaller areas typical of serous differentiation and
      rare microfoci of endocervical-type mucinous epithelium. These features indicated
      multidirectional Mullerian differentiation in a process that, overall, was
      consistent with so called florid cystic endosalpingiosis. This lesion is to be
      distinguished from other benign conditions including multicystic mesothelioma,
      endometriosis, endocervicosis, florid deep glands of the uterine cervix, and deep
      Nabothian cysts of the uterine cervix.

PMID- 11328843
TI  - Evaluation of extraction methods from paraffin wax embedded tissues for PCR
      amplification of human and viral DNA.
AB  - AIM: To evaluate the efficiency of phenol/chloroform, microwave, and Qiagen spin
      column based DNA extractions from paraffin wax embedded tissue for use in the
      polymerase chain reaction (PCR). In addition, to assess the reliability of
      amplifying a housekeeping gene to indicate successful viral DNA extraction.
      METHODS: DNA samples extracted from 20 blocks of cervical carcinoma tissues using
      the three methods were subjected to PCRs targeting 509 bp and 355 bp of the beta
      globin gene, and 450 bp and 150 bp of human papillomavirus (HPV) DNA. RESULTS:
      Microwave extraction showed the highest positive rate for beta globin PCR,
      whereas the spin column method was the most efficient for HPV DNA extraction.
      When the 509 bp beta globin and 450 bp HPV PCR results were correlated, two of
      10, eight of 12, and nine of 10 beta globin positive extractions prepared by
      means of the phenol/chloroform, microwave, and spin column methods, respectively,
      yielded HPV DNA of the expected size. For the beta globin negative samples, HPV
      was detected in three of 10, two of eight, and four of 10 samples. CONCLUSIONS:
      HPV DNA extraction was most efficient using the Qiagen spin column and had the
      highest positive predictive value when a housekeeping gene was used as an
      indicator of successful viral DNA extraction; the phenol/chloroform method was
      the least efficient. The potential drawbacks of some extraction methods when
      using a human housekeeping gene to assess the quality of viral DNA extraction
      need to be considered.

PMID- 11328844
TI  - Giant cell tumour of tendon sheath (localised nodular tenosynovitis):
      clinicopathological features of 71 cases.
AB  - AIMS/BACKGROUND: Giant cell tumour of the tendon sheath (GCTTS) is regarded as
      the most common neoplasm of the hand that can recur after excision. The objective
      of this study was to review a series of cases in our department and to determine
      any clinical or pathological features that might predict the likelihood of
      recurrence. METHODS: Clinical data, obtained from pathology request forms and in
      patient notes, along with the gross and microscopic appearances of 71 cases of
      GCTTS were evaluated. RESULTS: Clinical features and pathological features
      identified were similar to those of previous studies. In comparison with previous
      studies a higher mitotic count (range, 1-21 mitoses/10 high power fields (HPF);
      mean, 5/10 HPF) was noted in all cases, irrespective of recurrence and numerous
      apoptotic bodies (up to 30/10 HPF), mainly formed from osteoclast-like giant
      cells, were present. CONCLUSIONS: GCTTS is a relatively rare soft tissue tumour
      of uncertain histiogenesis. Mitotic and apoptotic figures are a common feature
      and do not indicate clinical behaviour. Complete local excision is the treatment
      of choice.

PMID- 11328845
TI  - Role of screening agar plates for in vitro susceptibility testing of Helicobacter
      pylori in a routine laboratory setting.
AB  - BACKGROUND: Resistance of Helicobacter pylori to the more frequently used
      antibiotics (metronidazole and clarithromycin) reduces eradication rates even
      with triple treatment. Determining the antibiogram profile of H pylori can take
      up to 14 days and delays appropriate treatment. AIMS: To determine the role of
      screening agar plates for more rapid in vitro susceptibility of H pylori to
      metronidazole, amoxicillin, and clarithromycin. METHODS: Routine gastric biopsy
      specimens from 507 dyspeptic patients were inoculated on to 10% lysed blood agar
      plates containing metronidazole (8 microg/ml), clarithromycin (2 microg/ml), or
      amoxicillin (0.5 microg/ml). The minimum inhibitory concentration (MIC) of the 90
      isolates was determined using the E test. RESULTS: Metronidazole resistance was
      detected in 28 of 90 isolates by E test and nine of 98 by screening agar. The
      screening agar detected none of the four clarithromycin resistant isolates
      detected by the E test. CONCLUSIONS: The screening agar method is not
      sufficiently sensitive to be used alone.

PMID- 11328846
TI  - A case of purple urine bag syndrome associated with Providencia rettgeri.

PMID- 11328847
TI  - Fatal legionella pneumonia after fludarabine treatment in chronic lymphocytic
      leukaemia.

PMID- 11328848
TI  - Bones, groans, moans... and salivary stones?

PMID- 11328849
TI  - Handling of renal biopsies: different approaches reflect a lack of evidence for
      what constitutes "best practice".

PMID- 11328850
TI  - Is it useful to test for antibodies to extractable nuclear antigens in the
      presence of a negative antinuclear antibody on Hep-2 cells?

PMID- 11328851
TI  - Evolution and classification of cystine knot-containing hormones and related
      extracellular signaling molecules.
AB  - The cystine knot three-dimensional structure is found in many extracellular
      molecules and is conserved among divergent species. The identification of
      proteins with a cystine knot structure is difficult by commonly used pairwise
      alignments because the sequence homology among these proteins is low. Taking
      advantage of complete genome sequences in diverse organisms, we used a
      complementary approach of pattern searches and pairwise alignments to screen the
      predicted protein sequences of five model species (human, fly, worm, slime mold,
      and yeast) and retrieved proteins with low sequence homology but containing a
      typical cystine knot signature. Sequence comparison between proteins known to
      have a cystine knot three-dimensional structure (transforming growth factor-beta,
      glycoprotein hormone, and platelet-derived growth factor subfamily members)
      identified new crucial amino acid residues (two hydrophilic amino acid residues
      flanking cysteine 5 of the cystine knot). In addition to the well known members
      of the cystine knot superfamily, novel subfamilies of proteins (mucins, norrie
      disease protein, von Willebrand factor, bone morphogenetic protein antagonists,
      and slit-like proteins) were identified as putative cystine knot-containing
      proteins. Phylogenetic analysis revealed the ancient evolution of these proteins
      and the relationship between hormones [e.g. transforming growth factor-beta
      (TGFbeta)] and extracellular matrix proteins (e.g. mucins). They are absent in
      the unicellular yeast genome but present in nematode, fly, and higher species,
      indicating that the cystine knot structure evolved in extracellular signaling
      molecules of multicellular organisms. All data retrieved by this study can be
      viewed at http://hormone.stanford.edu/.

PMID- 11328852
TI  - Binding of agonist but not antagonist leads to fluorescence resonance energy
      transfer between intrinsically fluorescent gonadotropin-releasing hormone
      receptors.
AB  - We have used spot fluorescence photobleaching recovery methods to measure the
      lateral diffusion of GnRH receptor (GnRHR) fused at its C terminus to green
      fluorescent protein (GFP) after binding of either GnRH agonists or antagonist.
      Before ligand binding, GnRHR-GFP exhibited fast rates of lateral diffusion (D =
      18 +/- 2.8 x 10(-10)cm2 x sec(-1)) and high values for fractional fluorescence
      recovery (%R) after photobleaching (73 +/- 1%). Increasing concentrations of
      agonists, GnRH or D-Ala6-GnRH, caused a dose-dependent slowing of receptor
      lateral diffusion as well as a decreased fraction of mobile receptors. Increasing
      concentrations of the GnRH antagonist Antide slowed the rate of receptor
      diffusion but had no effect on the fraction of mobile receptors, which remained
      high. To determine whether the decrease in %R caused by GnRH agonists was due, in
      part, to increased receptor self-association, we measured the fluorescence
      resonance energy transfer efficiency between GnRHR-GFP and yellow fluorescent
      protein-GNRHR: There was no energy transfer between GnRHR on untreated cells.
      Treatment of cells with GnRH agonists led to a concentration-dependent increase
      in the energy transfer between GnRH receptors to a maximum value of 16 +/- 1%.
      There was no significant energy transfer between GnRH receptors on cells treated
      with Antide, even at a concentration of 100 nM. These data provide direct
      evidence that, before binding of ligand, GnRHR exists as an isolated receptor and
      that binding of GnRH agonists, but not antagonist, leads to formation of large
      complexes that exhibit slow diffusion and contain receptors that are self
      associated.

PMID- 11328853
TI  - Activation of the rat follicle-stimulating hormone receptor promoter by
      steroidogenic factor 1 is blocked by protein kinase a and requires upstream
      stimulatory factor binding to a proximal E box element.
AB  - The receptor for the pituitary glycoprotein hormone FSH (FSHR) and the nuclear
      hormone receptor steroidogenic factor 1 (SF-1) play important roles in control of
      the hypothalamic-pituitary- gonadal axis. FSHR is essential for integrating the
      pituitary FSH signal to gonadal response, while SF-1 is an important
      transcriptional regulator of many genes that function within this axis and is
      essential for the development of gonads and adrenal glands. Given the critical
      role of SF-1 in regulation of the gonads and the coexpression of FSHR and SF-1 in
      Sertoli and granulosa cells, we examined the ability of SF-1 to regulate
      transcription of the FSHR gene. We found that SF-1 stimulated rat FSHR promoter
      activity in a dose-dependent and promoter-specific manner. Examination of various
      promoter deletion mutants indicated that SF-1 acts through the proximal promoter
      region and upstream promoter sequences. An E box element within the proximal
      promoter is essential for activation of the FSHR promoter by SF-1. This element
      binds the transcriptional regulators USF1 and USF2 (upstream stimulatory factors
      1 and 2) but not SF-1, as shown by electrophoretic mobility shift assays. In
      addition, functional studies identified a requirement for the USF proteins in SF
      1 activation of FSHR and mapped an important regulatory domain within exons 4 and
      5 of USF2. Cotransfection studies revealed that activation of protein kinase A
      leads to inhibition of SF-1-stimulated transcription of FSHR, while it synergized
      with SF-1 to activate the equine LH beta-promoter (ebeta). Thus, stimulation of
      the cAMP pathway differentially regulates SF-1 activation of the FSHR and ebeta
      promoters.

PMID- 11328854
TI  - Developmental regulation of mitogen-activated protein kinase-activated kinases-2
      and -3 (MAPKAPK-2/-3) in vivo during corpus luteum formation in the rat.
AB  - The current study investigates the activation in vivo and regulation of the
      expression of components of the p38 mitogen-activated protein kinase (MAPK)
      pathway during gonadotropin-induced formation and development of the rat corpus
      luteum, employing a sequential PMSG/human CG (hCG) treatment paradigm. We
      postulated that the p38 MAPK pathway could serve to promote phosphorylation of
      key substrates during luteal maturation, since maturing luteal cells, thought to
      be cAMP-nonresponsive, nevertheless maintain critical phosphoproteins. Both p38
      MAPK and its upstream activator MAPK kinase-6 (MKK6) were found to be chronically
      activated during the luteal maturation phase, with activation detected by 24 h
      post hCG and maintained through 4 days post hCG. The p38 MAPK downstream protein
      kinase target termed MAPK-activated protein kinase-3 (MAPKAPK-3) was newly
      induced at both mRNA and protein levels during luteal formation and maturation,
      while mRNA and protein expression of the closely related MAPKAPK-2 diminished.
      Two potential substrates for MAPKAPKs, the small heat shock protein HSP-27 and
      the cAMP regulatory element binding protein CREB, were monitored in vivo for
      phosphorylation. HSP-27 phosphorylation was not modulated during luteal
      maturation. In contrast, we observed sustained luteal-phase CREB phosphorylation
      in vivo, consistent with upstream MKK6/p38 MAPK activation and MAPKAPK-3
      induction. MAPKAPK-3-specific immune complex kinase assays provided direct
      evidence that MAPKAPK-3 was in an activated state during luteal maturation in
      vivo. Cellular inhibitor studies indicated that an intact p38 MAPK path was
      required for CREB phosphorylation in a cellular model of luteinization, as
      treatment of luteinized granulosa cells with the p38 MAPK inhibitor SB 203580
      strongly inhibited CREB phosphorylation. Transient transfection studies provided
      direct evidence that MAPKAPK-3 was capable of signaling to activate CREB
      transcriptional activity, as assessed by means of GAL4-CREB fusion protein
      construct coexpressed with GAL4-luciferase reporter construct. Introduction of
      wild-type, but not kinase-dead mutant, MAPKAPK-3 cDNA, into a mouse ovarian cell
      line stimulated GAL4-CREB- dependent transcriptional activity approximately 3
      fold. Thus MAPKAPK-3 is indeed uniquely poised to support luteal maturation
      through the phosphorylation and activation of the nuclear transcription factor
      CREB.

PMID- 11328855
TI  - A single Pitx1 binding site is essential for activity of the LHbeta promoter in
      transgenic mice.
AB  - Reproduction depends on regulated expression of the LHbeta gene. Tandem copies of
      regulatory elements that bind early growth response protein 1 (Egr-1) and
      steroidogenic factor 1 (SF-1) are located in the proximal region of the LHbeta
      promoter and make essential contributions to its activity as well as mediate
      responsiveness to GNRH: Located between these tandem elements is a single site
      capable of binding the homeodomain protein Pitx1. From studies that employ
      overexpression paradigms performed in heterologous cell lines, it appears that
      Egr-1, SF-1, and Pitx1 interact cooperatively through a mechanism that does not
      require the binding of Pitx1 to its site. Since the physiological ramifications
      of these overexpression studies remain unclear, we reassessed the requirement for
      a Pitx1 element in the promoter of the LHbeta gene using homologous cell lines
      and transgenic mice, both of which obviate the need for overexpression of
      transcription factors. Our analysis indicated a striking requirement for the
      Pitx1 regulatory element. When assayed by transient transfection using a
      gonadotrope-derived cell line (LbetaT2), an LHbeta promoter construct harboring a
      mutant Pitx1 element displayed attenuated transcriptional activity but retained
      responsiveness to GNRH: In contrast, analysis of wild-type and mutant expression
      vectors in transgenic mice indicated that LHbeta promoter activity is completely
      dependent on the presence of a functional Pitx1 binding site. Indeed, the
      dependence on an intact Pitx1 binding site in transgenic mice is so strict that
      responsiveness to GnRH is also lost, suggesting that the mutant promoter is
      inactive. Collectively, our data reinforce the concept that activity of the
      LHbeta promoter is determined, in part, through highly cooperative interactions
      between SF-1, Egr-1, and Pitx1. While Egr-1 can be regarded as a key downstream
      effector of GnRH, and Pitx1 as a critical partner that activates SF-1, our data
      firmly establish that the Pitx1 element plays a vital role in permitting these
      functions to occur in vivo.

PMID- 11328856
TI  - Cloning and characterization of a rat ortholog of MMP-23 (matrix
      metalloproteinase-23), a unique type of membrane-anchored matrix
      metalloproteinase and conditioned switching of its expression during the ovarian
      follicular development.
AB  - In our attempt to study the role of matrix metalloproteinases (MMPs) in the
      process of mammalian ovulation, we isolated a rat ortholog of the recently
      reported human MMP-23 from gonadotropin-primed immature rat ovaries. Transient
      expression of epitope-tagged rat and human MMP-23 in COS-1 cells revealed that
      they were synthesized as a membrane-anchored glycoprotein with type II topology.
      Indirect immunofluorescent analysis showed that subcellular localization of MMP
      23 was predominantly in the perinuclear regions. The transfected human MMP-23
      protein was processed endogenously to the soluble form in COS-1 cells. However,
      cotransfection of MMP-23 with the mouse furin cDNA did not enhance this
      processing, indicating that furin may not be involved in this event. Notably, in
      situ hybridization analysis revealed a dramatic switching of MMP-23 mRNA
      localization from granulosa cells to theca-externa/fibroblasts and ovarian
      surface epithelium during the follicular development. In serum-free primary
      culture of rat granulosa cells, a drastic diminution of MMP-23 mRNA expression
      was observed in response to FSH action between 24 h and 48 h of culture. The
      observed effect of FSH on MMP-23 expression was mimicked by treatment of
      granulosa cells with forskolin or 8-bromo (Br)-cAMP. In contrast, MMP-23 mRNA
      levels increased in theca-interstitial cells regardless of the presence of LH in
      the culture. However, treatment of theca-interstitial cells with forskolin or 8
      Br-cAMP markedly reduced the expression of MMP-23 with a concomitant increase in
      progesterone production. These results indicate that the MMP-23 gene is spatially
      and temporally regulated in a cell type-specific manner in ovary via the cAMP
      signaling pathway.

PMID- 11328857
TI  - Androgen-driven prostate epithelial cell proliferation and differentiation in
      vivo involve the regulation of p27.
AB  - Androgens control both growth and differentiation of the normal prostate gland.
      However, the mechanisms by which androgens act upon the cell cycle machinery to
      regulate these two fundamental processes are largely unknown. The cyclin
      dependent kinase (cdk) inhibitor p27 is a negative cell cycle regulator involved
      in differentiation-associated growth arrest. Here, we investigate the role and
      regulation of p27 in the testosterone proprionate (TP)-stimulated regeneration of
      the ventral prostate (VP) of castrated rats. Continuous TP administration to
      castrated rats triggered epithelial cell proliferation, which peaked at 72 h, and
      then declined despite further treatment. Castration-induced atrophy of the VP was
      associated with a significant increase in p27 expression as compared with the VP
      of intact animals. Twelve hours after the initiation of androgen treatment, total
      p27 levels as well as its fraction bound to cdk2, its main target, significantly
      dropped in the VP of castrated rats. Thereafter, concomitantly to the induction
      of epithelial cell proliferation, the glandular morphology of VP was
      progressively restored at 48-96 h of TP treatment. During this period of the
      regenerative process, whereas both proliferating basal and secretory epithelial
      cells did not express p27, the protein was selectively up-regulated in the
      nonproliferating secretory epithelial compartment. This up-regulation of p27
      expression was coincident with an increase in its association with, and
      presumably inhibition of, cdk2. At each time point of TP treatment, p27 abundance
      in the VP was inversely correlated with the level of its proteasome-dependent
      degradation activity measured in vitro in VP lysates, whereas only slight changes
      in the amount of p27 transcripts were detected. In addition, the antiandrogen
      flutamide blocked maximal TP-induced p27 degradation completely. Finally, the
      expression of skp2, the ubiquitin ligase that targets p27 for degradation, was
      seen to increase with androgen administration, preceding maximal proliferation
      and concomitantly to augmented p27 degradation activity. Taken together, our data
      indicate that androgens mediate both proliferation and differentiation signals in
      normal prostate epithelial cells in vivo, through regulation of p27.

PMID- 11328858
TI  - Subcellular localization of the steroid receptor coactivators (SRCs) and MEF2 in
      muscle and rhabdomyosarcoma cells.
AB  - Skeletal muscle differentiation and the activation of muscle-specific gene
      expression are dependent on the concerted action of the MyoD family and the MADS
      protein, MEF2, which function in a cooperative manner. The steroid receptor
      coactivator SRC-2/GRIP-1/TIF-2, is necessary for skeletal muscle differentiation,
      and functions as a cofactor for the transcription factor, MEF2. SRC-2 belongs to
      the SRC family of transcriptional coactivators/cofactors that also includes SRC-1
      and SRC-3/RAC-3/ACTR/AIB-1. In this study we demonstrate that SRC-2 is
      essentially localized in the nucleus of proliferating myoblasts; however, weak
      (but notable) expression is observed in the cytoplasm. Differentiation induces a
      predominant localization of SRC-2 to the nucleus; furthermore, the nuclear
      staining is progressively more localized to dot-like structures or nuclear
      bodies. MEF2 is primarily expressed in the nucleus, although we observed a mosaic
      or variegated expression pattern in myoblasts; however, in myotubes all nuclei
      express MEF2. GRIP-1 and MEF2 are coexpressed in the nucleus during skeletal
      muscle differentiation, consistent with the direct interaction of these proteins.
      Rhabdomyosarcoma (RMS) cells derived from malignant skeletal muscle tumors have
      been proposed to be deficient in cofactors. Alveolar RMS cells very weakly
      express the steroid receptor coactivator, SRC-2, in a diffuse nucleocytoplasmic
      staining pattern. MEF2 and the cofactors, SRC-1 and SRC-3 are abundantly
      expressed in alveolar and embryonal RMS cells; however, the staining is not
      localized to the nucleus. Furthermore, the subcellular localization and
      transcriptional activity of MEF2C and a MEF2-dependent reporter are compromised
      in alveolar RMS cells. In contrast, embryonal RMS cells express SRC-2 in the
      nucleus, and MEF2 shuttles from the cytoplasm to the nucleus after serum
      withdrawal. In conclusion, this study suggests that the steroid receptor
      coactivator SRC-2 and MEF2 are localized to the nucleus during the
      differentiation process. In contrast, RMS cells display aberrant transcription
      factor SRC localization and expression, which may underlie certain features of
      the RMS phenotype.

PMID- 11328860
TI  - Functions of the upstream and proximal steroidogenic factor 1 (SF-1)-binding
      sites in the CYP11A1 promoter in basal transcription and hormonal response.
AB  - The CYP11A1 gene encodes P450scc (cholesterol side-chain cleavage enzyme), which
      catalyzes the first step for the synthesis of steroids. Expression of CYP11A1 is
      controlled by transcription factor SF-1 (steroidogenic factor 1). Two functional
      SF-1-binding sites, P and U, located at -40 and -1,600 regions of the CYP11A1
      gene, have been identified, but their exact functions with respect to basal
      activation vs. cAMP response have not been dissected. We have addressed this
      question by examining the ability of the mutated human CYP11A1 promoter to drive
      LacZ reporter gene expression in transgenic mouse lines. The activity of the mtP
      mutant promoter was greatly reduced, indicating the importance of the P site.
      Mutation of the upstream U site also resulted in reduced reporter gene
      expression, but some residual activity remained. This residual reporter gene
      activity was detected in the adrenal and gonad in a tissue-specific manner. ACTH
      and hCG can stimulate LacZ gene expression in the adrenals and testes of
      transgenic mice driven by the wild-type but not the mtU promoter. These results
      indicate that the upstream SF-1-binding site is required for hormonal
      stimulation. Our experiments demonstrate the participation of both the proximal
      and the upstream SF-1-binding sites in hormone-responsive transcription.

PMID- 11328859
TI  - Cyclin D1 binds the androgen receptor and regulates hormone-dependent signaling
      in a p300/CBP-associated factor (P/CAF)-dependent manner.
AB  - The androgen receptor (AR) is a ligand-regulated member of the nuclear receptor
      superfamily. The cyclin D1 gene product, which encodes the regulatory subunit of
      holoenzymes that phosphorylate the retinoblastoma protein (pRB), promotes
      cellular proliferation and inhibits cellular differentiation in several different
      cell types. Herein the cyclin D1 gene product inhibited ligand-induced AR-
      enhancer function through a pRB-independent mechanism requiring the cyclin D1
      carboxyl terminus. The histone acetyltransferase activity of P/CAF (p300/CBP
      associated factor) rescued cyclin D1-mediated AR trans-repression. Cyclin D1 and
      the AR both bound to similar domains of P/CAF, and cyclin D1 displaced binding of
      the AR to P/CAF in vitro. These studies suggest cyclin D1 binding to the AR may
      repress ligand-dependent AR activity by directly competing for P/CAF binding.

PMID- 11328861
TI  - Transcriptional regulation of vascular endothelial growth factor expression in
      epithelial and stromal cells during mouse mammary gland development.
AB  - Accompanying changes in the development and function of the mammary gland is the
      establishment of a vascular network of critical importance for lactogenesis and
      tumorigenesis. A potent angiogenic and permeability factor that regulates
      vascular development in association with epithelial-stromal interactions is
      vascular endothelial growth factor (VEGF). Analysis of VEGF transcription by RT
      PCR revealed mRNA for all three VEGF isoforms (VEGF120, 164, 188) within the
      mammary gland of nulliparous females. During pregnancy the level of VEGF188
      declined and became undetectable during lactation in association with the
      increased abundance of VEGF120 and VEGF164 mRNAS: All three isoforms were
      expressed at consistent levels within the cleared mammary fat pad throughout
      development. Furthermore, the presence of VEGF188 mRNA in omental adipose tissue
      at various stages established that VEGF188 is expressed specifically in adipose
      tissue within the mammary gland. Using 3T3-L1 preadipocytes it was demonstrated
      that VEGF188 mRNA transcription occurs as a late event during lipogenesis
      distinct from earlier induction of VEGF120 and VEGF164 mRNA during
      differentiation. In contrast, HC11 mammary epithelial cells only expressed mRNA
      for VEGF120 and VEGF164. Localization of VEGF mRNA and protein revealed that VEGF
      is expressed in stromal cells of the mammary gland in nulliparous females and
      then undergoes a transition to epithelial expression during lactation. By
      contrast, mRNA for the VEGF receptors, Flk-1 and Flt-1, localized to stromal
      cells within the mammary fat pad during virgin and gestational development and
      was expressed in the interstitial tissue basal to epithelial cells during
      lactation. Taken together, these results support the conclusion that VEGF is
      differentially transcribed by specific cell types within the mammary gland, and
      that under hormonal regulation it functions in an autocrine/paracrine manner.

PMID- 11328863
TI  - Proposal for a unified CCN nomenclature.

PMID- 11328862
TI  - Activation and association of the Tec tyrosine kinase with the human prolactin
      receptor: mapping of a Tec/Vav1-receptor binding site.
AB  - Stimulation of the PRL receptor (PRLr) results in the activation of the guanine
      nucleotide exchange factor (GEF) p95Vav1 with corresponding alterations in
      cytoarchitecture and cell motility. To better understand the mechanisms involved
      in the regulation of Vav1 activity, the role of the tyrosine kinase p70Tec was
      examined. Coimmunoprecipitation and in vitro kinase assays revealed that ligand
      stimulation of the PRLr resulted in the rapid activation of Tec and its
      concomitant association with the PRLR: When coexpressed in COS-1 cells, both Vav1
      and Tec were found to associate with the PRLr in the presence of ligand. In the
      absence of receptor, a constitutive complex between Vav1 and Tec was noted. Both
      Vav1 and Tec, however, were capable of independent engagement of a bipartite
      intracellular domain of the PRLR: Deletion mapping studies confined this
      interaction to residues 323 to 527 of the intracellular domain of the PRLR:
      Furthermore, Tec enhanced the GEF activity of Vav1 as evidenced by an increase in
      GTP-bound Rac1. These data would suggest a pivotal function for the formation of
      a Tec/Vav1/PRLr complex during PRL-driven signal transduction, given the role of
      Vav1 in the control of cell proliferation and the regulation of Rho family
      mediated cytoskeletal alterations.

PMID- 11328864
TI  - Abstracts from the first international workshop on the CCN family of genes, 17-19
      October 2000, Saint-Malo, France.

PMID- 11328866
TI  - An AU-box motif upstream of the SD sequence of light-dependent psbA transcripts
      confers mRNA instability in darkness in cyanobacteria.
AB  - The psbA2 gene of a unicellular cyanobacterium, Microcystis aeruginosa K-81,
      encodes a D1 protein homolog in the reaction center of photosynthetic Photosystem
      II. The expression of the psbA2 transcript has been shown to be light-dependent
      as assessed under light and dark (12/12 h) cycling conditions. We aligned the 5'
      untranslated leader regions (UTRs) of psbAs from different photosynthetic
      organisms and identified a conserved sequence, UAAAUAAA or the 'AU-box', just
      upstream of the SD sequences. To clarify the role of 5'-upstream cis-elements
      containing the AU-box for light-dependent expression of psbA2, a series of
      deletion and point mutations in the region were introduced into the genome of
      heterologous cyanobacterium Synechococcus sp. strain PCC 7942, and psbA2
      expression was examined. A clear pattern of light-dependent expression was
      observed in recombinant cyanobacteria carrying the K-81 psbA2 -38/+36 region
      (which includes the minimal promoter element and a light-dependent cis-element
      with the AU-box), +1 indicating the transcription start site. A constitutive
      pattern of expression, in which the transcripts remained almost stable under dark
      conditions, was obtained in cells harboring the -38/+14 region (the minimal
      element), indicating that the +14/+36 region with the AU-box is important for the
      observed light-dependent expression. Point mutations analyses within the AU-box
      also revealed that changes in number, direction and identity (as assayed by
      adenine/uridine nucleotide substitutions) influenced the light-dependent pattern
      of expression. The level of psbA2 transcripts increased markedly in CG- or
      deletion-box mutants in the dark, strongly indicating that the AU- (AT-) box acts
      as a negative cis-element. Furthermore, characterization of transcript
      accumulation in cells treated with rifampicin suggests that psbA2 5'-mRNA is
      unstable in the dark, supporting the view that the light-dependent expression is
      controlled at the post-transcriptional level. We discuss various mechanisms that
      may lead to altered mRNA stability such as the binding of factor(s) or ribosomes
      to the 5'-UTR and possible roles of the AU-box motif and the SD sequence.

PMID- 11328867
TI  - Characterisation of the gene encoding type II DNA topoisomerase from Leishmania
      donovani: a key molecular target in antileishmanial therapy.
AB  - The gene encoding type II DNA topoisomerase from the kinetoplastid
      hemoflagellated protozoan parasite Leishmania donovani (LdTOP2) was isolated from
      a genomic DNA library of this parasite. DNA sequence analysis revealed an ORF of
      3711 bp encoding a putative protein of 1236 amino acids with no introns. The
      deduced amino acid sequence of LdTOP2 showed strong homologies to TOP2 sequences
      from other kinetoplastids, namely Crithidia and Trypanosoma spp. with estimated
      identities of 86 and 68%, respectively. LdTOP2 shares a much lower identity of
      32% with its human homologue. LdTOP2 is located as a single copy on a chromosome
      in the 0.7 Mb region in the L.donovani genome and is expressed as a 5 kb
      transcript. 5'-Mapping studies indicate that the LdTOP2 gene transcript is
      matured post-transcriptionally with the trans-splicing of the mini-exon occurring
      at -639 from the predicted initiation site. Antiserum raised in rabbit against
      glutathione S-transferase fusion protein containing the major catalytic portion
      of the recombinant L.donovani topoisomerase II protein could detect a band on
      western blots at approximately 132 kDa, the expected size of the entire protein.
      Use of the same antiserum for immunolocalisation analysis led to the
      identification of nuclear, as well as kinetoplast, antigens for L.donovani
      topoisomerase II. The in vitro biochemical properties of the full-length
      recombinant LdTOP2 when overexpressed in E.coli were similar to the Mg(II) and
      ATP-dependent activity found in cell extracts of L.donovani.

PMID- 11328865
TI  - Recent advances in the elucidation of the mechanisms of action of ribozymes.
AB  - The cleavage of RNA can be accelerated by a number of factors. These factors
      include an acidic group (Lewis acid) or a basic group that aids in the
      deprotonation of the attacking nucleophile, in effect enhancing the
      nucleophilicity of the nucleophile; an acidic group that can neutralize and
      stabilize the leaving group; and any environment that can stabilize the
      pentavalent species that is either a transition state or a short-lived
      intermediate. The catalytic properties of ribozymes are due to factors that are
      derived from the complicated and specific structure of the ribozyme-substrate
      complex. It was postulated initially that nature had adopted a rather narrowly
      defined mechanism for the cleavage of RNA. However, recent findings have clearly
      demonstrated the diversity of the mechanisms of ribozyme-catalyzed reactions.
      Such mechanisms include the metal-independent cleavage that occurs in reactions
      catalyzed by hairpin ribozymes and the general double-metal-ion mechanism of
      catalysis in reactions catalyzed by the Tetrahymena group I ribozyme.
      Furthermore, the architecture of the complex between the substrate and the
      hepatitis delta virus ribozyme allows perturbation of the pK(a) of ring nitrogens
      of cytosine and adenine. The resultant perturbed ring nitrogens appear to be
      directly involved in acid/base catalysis. Moreover, while high concentrations of
      monovalent metal ions or polyamines can facilitate cleavage by hammerhead
      ribozymes, divalent metal ions are the most effective acid/base catalysts under
      physiological conditions.

PMID- 11328868
TI  - Targeting peptide nucleic acid (PNA) oligomers to mitochondria within cells by
      conjugation to lipophilic cations: implications for mitochondrial DNA
      replication, expression and disease.
AB  - The selective manipulation of mitochondrial DNA (mtDNA) replication and
      expression within mammalian cells has proven difficult. One promising approach is
      to use peptide nucleic acid (PNA) oligomers, nucleic acid analogues that bind
      selectively to complementary DNA or RNA sequences inhibiting replication and
      translation. However, the potential of PNAs is restricted by the difficulties of
      delivering them to mitochondria within cells. To overcome this problem we
      conjugated a PNA 11mer to a lipophilic phosphonium cation. Such cations are taken
      up by mitochondria through the lipid bilayer driven by the membrane potential
      across the inner membrane. As anticipated, phosphonium-PNA (ph-PNA) conjugates of
      3.4-4 kDa were imported into both isolated mitochondria and mitochondria within
      human cells in culture. This was confirmed by using an ion-selective electrode to
      measure uptake of the ph-PNA conjugates; by cell fractionation in conjunction
      with immunoblotting; by confocal microscopy; by immunogold-electron microscopy;
      and by crosslinking ph-PNA conjugates to mitochondrial matrix proteins. In all
      cases dissipating the mitochondrial membrane potential with an uncoupler
      prevented ph-PNA uptake. The ph-PNA conjugate selectively inhibited the in vitro
      replication of DNA containing the A8344G point mutation that causes the human
      mtDNA disease 'myoclonic epilepsy and ragged red fibres' (MERRF) but not the wild
      type sequence that differs at a single nucleotide position. Therefore these
      modified PNA oligomers retain their selective binding to DNA and the lipophilic
      cation delivers them to mitochondria within cells. When MERRF cells were
      incubated with the ph-PNA conjugate the ratio of MERRF to wild-type mtDNA was
      unaffected, even though the ph-PNA content of the mitochondria was sufficient to
      inhibit MERRF mtDNA replication in a cell-free system. This unexpected finding
      suggests that nucleic acid derivatives cannot bind their complementary sequences
      during mtDNA replication. In summary, we have developed a new strategy for
      targeting PNA oligomers to mitochondria and used it to determine the effects of
      PNA on mutated mtDNA replication in cells. This work presents new approaches for
      the manipulation of mtDNA replication and expression, and will assist in the
      development of therapies for mtDNA diseases.

PMID- 11328869
TI  - Cleavage of poly(A) tails on the 3'-end of RNA by ribonuclease E of Escherichia
      coli.
AB  - RNase E initiates the decay of Escherichia coli RNAs by cutting them internally
      near their 5'-end and is a component of the RNA degradosome complex, which also
      contains the 3'-exonuclease PNPASE: Recently, RNase E has been shown to be able
      to remove poly(A) tails by what has been described as an exonucleolytic process
      that can be blocked by the presence of a phosphate group on the 3'-end of the
      RNA. We show here, however, that poly(A) tail removal by RNase E is in fact an
      endonucleolytic process that is regulated by the phosphorylation status at the 5'
      but not the 3'-end of RNA. The rate of poly(A) tail removal by RNase E was found
      to be 30-fold greater when the 5'-terminus of RNA substrates was converted from a
      triphosphate to monophosphate group. This finding prompted us to re-analyse the
      contributions of the ribonucleolytic activities within the degradosome to 3'
      attack since previous studies had only used substrates that had a triphosphate
      group on their 5'-end. Our results indicate that RNase E associated with the
      degradosome may contribute to the removal of poly(A) tails from 5'
      monophosphorylated RNAs, but this is only likely to be significant should their
      attack by PNPase be blocked.

PMID- 11328870
TI  - Human testis expresses a specific poly(A)-binding protein.
AB  - In testis mRNA stability and translation initiation are extensively under the
      control of poly(A)-binding proteins (PABP). Here we have cloned a new human
      testis-specific PABP (PABP3) of 631 amino acids (70.1 kDa) with 92.5% identical
      residues to the ubiquitous PABP1. A northern blot of multiple human tissues
      hybridised with PABP3- and PABP1-specific oligonucleotide probes revealed two
      PABP3 mRNAs (2.1 and 2.5 kb) detected only in testis, whereas PABP1 mRNA (3.2 kb)
      was present in all tested tissues. In human adult testis, PABP3 mRNA expression
      was restricted to round spermatids, whereas PABP1 was expressed in these cells as
      well as in pachytene spermatocytes. PABP3-specific antibodies identified a
      protein of 70 kDa in human testis extracts. This protein binds poly(A) with a
      slightly lower affinity as compared to PABP1. The human PABP3 gene is intronless
      with a transcription start site 61 nt upstream from the initiation codon. A
      sequence of 256 bp upstream from the transcription start site drives the promoter
      activity of PABP3 and its tissue-specific expression. The expression of PABP3
      might be a way to bypass PABP1 translational repression and to produce the amount
      of PABP needed for active mRNA translation in spermatids.

PMID- 11328871
TI  - Cloning the human and mouse MMS19 genes and functional complementation of a yeast
      mms19 deletion mutant.
AB  - The MMS19 gene of the yeast Saccharomyces cerevisiae encodes a polypeptide of
      unknown function which is required for both nucleotide excision repair (NER) and
      RNA polymerase II (RNAP II) transcription. Here we report the molecular cloning
      of human and mouse orthologs of the yeast MMS19 gene. Both human and Drosophila
      MMS19 cDNAs correct thermosensitive growth and sensitivity to killing by UV
      radiation in a yeast mutant deleted for the MMS19 gene, indicating functional
      conservation between the yeast and mammalian gene products. Alignment of the
      translated sequences of MMS19 from multiple eukaryotes, including mouse and
      human, revealed the presence of several conserved regions, including a HEAT
      repeat domain near the C-terminus. The presence of HEAT repeats, coupled with
      functional complementation of yeast mutant phenotypes by the orthologous protein
      from higher eukaryotes, suggests a role of Mms19 protein in the assembly of a
      multiprotein complex(es) required for NER and RNAP II transcription. Both the
      mouse and human genes are ubiquitously expressed as multiple transcripts, some of
      which appear to derive from alternative splicing. The ratio of different
      transcripts varies in several different tissue types.

PMID- 11328872
TI  - Modular construction for function of a ribonucleoprotein enzyme: the catalytic
      domain of Bacillus subtilis RNase P complexed with B. subtilis RNase P protein.
AB  - The bacterial RNase P holoenzyme catalyzes the formation of the mature 5'-end of
      tRNAs and is composed of an RNA and a protein subunit. Among the two folding
      domains of the RNase P RNA, the catalytic domain (C-domain) contains the active
      site of this ribozyme. We investigated specific binding of the Bacillus subtilis
      C-domain with the B.subtilis RNase P protein and examined the catalytic activity
      of this C-domain-P protein complex. The C-domain forms a specific complex with
      the P protein with a binding constant of approximately 0.1 microM. The C-domain-P
      protein complex and the holoenzyme are equally efficient in cleaving single
      stranded RNA (approximately 0.9 min(-1) at pH 7.8) and substrates with a hairpin
      loop 3' to the cleavage site (approximately 40 min(-1)). The holoenzyme reaction
      is much more efficient with a pre-tRNA substrate, binding at least 100-fold
      better and cleaving 10-500 times more efficiently. These results demonstrate that
      the RNase P holoenzyme is functionally constructed in three parts. The catalytic
      domain alone contains the active site, but has little specificity and affinity
      for most substrates. The specificity and affinity for the substrate is generated
      by either the specificity domain of RNase P RNA binding to a T stem-loop-like
      hairpin or RNase P protein binding to a single-stranded RNA. This modular
      construction may be exploited to obtain RNase P-based ribonucleoprotein complexes
      with altered substrate specificity.

PMID- 11328873
TI  - Enhancing the catalytic repertoire of nucleic acids. II. Simultaneous
      incorporation of amino and imidazolyl functionalities by two modified
      triphosphates during PCR.
AB  - The incorporation of potentially catalytic groups into DNA is of interest for the
      in vitro selection of novel deoxyribozymes. We have devised synthetic routes to a
      series of three C7 modified 7-deaza-dATP derivatives with pendant aminopropyl, Z
      aminopropenyl and aminopropynyl side chains. These modified triphosphates have
      been tested as substrates for Taq polymerase during PCR. All the modifications
      are tolerated by this enzyme, with the aminopropynyl side chain giving the best
      result. Most protein enzymes have more than one type of catalytic group located
      in their active site. By using C5-imidazolyl-modified dUTPs together with 3
      (aminopropynyl)-7-deaza-dATP in place of the natural nucleotides dTTP and dATP,
      we have demonstrated the simultaneous incorporation of both amino and imidazolyl
      moieties into a DNA molecule during PCR. The PCR product containing the four
      natural bases was fully digested by XbaI, while PCR products containing the
      modified 7-deaza-dATP analogues were not cleaved. Direct evidence for the
      simultaneous incorporation during PCR of an imidazole-modified dUTP and an amino
      modified 7-deaza-dATP has been obtained using mass spectrometry.

PMID- 11328874
TI  - Identifying ribozyme-accessible sites using NUH triplet-targeting gapmers.
AB  - Accurately identifying accessible sites in RNA is a critical prerequisite for
      optimising the cleavage efficiency of hammerhead ribozymes and other small
      nucleozymes. Here we describe a simple RNase H-based procedure to rapidly
      identify hammerhead ribozyme-accessible sites in gene length RNAS: Twelve semi
      randomised RNA-DNA-RNA chimeric oligonucleotide probes, known as 'gapmers', were
      used to direct RNase H cleavage of transcripts with the specificity expected for
      hammerhead ribozymes, i.e. after NUH sites (where H is A, C or U). Cleavage sites
      were identified simply by the mobility of RNase H cleavage products relative to
      RNA markers in denaturing polyacrylamide gels. Sites were identified in
      transcripts encoding human interleukin-2 and platelet-derived growth factor.
      Thirteen minimised hammerhead ribozymes, miniribozymes (Mrz), were synthesised
      and in vitro cleavage efficiency (37 degrees C, pH 7.6 and 1 mM MgCl2) at each
      site was analysed. Of the 13 Mrz, five were highly effective, demonstrating good
      initial rate constants and extents of cleavage. The speed and accuracy of this
      method commends its use in screening for hammerhead-accessible sites.

PMID- 11328875
TI  - Ethidium-dependent uncoupling of substrate binding and cleavage by Escherichia
      coli ribonuclease III.
AB  - Ethidium bromide (EB) is known to inhibit cleavage of bacterial rRNA precursors
      by Escherichia coli ribonuclease III, a dsRNA-specific nuclease. The mechanism of
      EB inhibition of RNase III is not known nor is there information on EB-binding
      sites in RNase III substrates. We show here that EB is a reversible, apparently
      competitive inhibitor of RNase III cleavage of small model substrates in vitro.
      Inhibition is due to intercalation, since (i) the inhibitory concentrations of EB
      are similar to measured EB intercalation affinities; (ii) substrate cleavage is
      not affected by actinomycin D, an intercalating agent that does not bind dsRNA;
      (iii) the EB concentration dependence of inhibition is a function of substrate
      structure. In contrast, EB does not strongly inhibit the ability of RNase III to
      bind substrate. EB also does not block substrate binding by the C-terminal dsRNA
      binding domain (dsRBD) of RNase III, indicating that EB perturbs substrate
      recognition by the N-terminal catalytic domain. Laser photocleavage experiments
      revealed two ethidium-binding sites in the substrate R1.1 RNA. One site is in the
      internal loop, adjacent to the scissile bond, while the second site is in the
      lower stem. Both sites consist of an A-A pair stacked on a CG pair, a motif which
      apparently provides a particularly favorable environment for intercalation. These
      results indicate an inhibitory mechanism in which EB site-specifically binds
      substrate, creating a cleavage-resistant complex that can compete with free
      substrate for RNase III. This study also shows that RNase III recognition and
      cleavage of substrate can be uncoupled and supports an enzymatic mechanism of
      dsRNA cleavage involving cooperative but not obligatorily linked actions of the
      dsRBD and the catalytic domain.

PMID- 11328876
TI  - A functional interaction of Ku with Werner exonuclease facilitates digestion of
      damaged DNA.
AB  - Werner syndrome (WS) is a premature aging disorder where the affected individuals
      appear much older than their chronological age. The single gene that is defective
      in WS encodes a protein (WRN) that has ATPase, helicase and 3'-->5' exonuclease
      activities. Our laboratory has recently uncovered a physical and functional
      interaction between WRN and the Ku heterodimer complex that functions in double
      strand break repair and V(D)J recombination. Importantly, Ku specifically
      stimulates the exonuclease activity of WRN. We now report that Ku enables the
      Werner exonuclease to digest through regions of DNA containing 8-oxoadenine and 8
      oxoguanine modifications, lesions that have previously been shown to block the
      exonuclease activity of WRN alone. These results indicate that Ku significantly
      alters the exonuclease function of WRN and suggest that the two proteins function
      concomitantly in a DNA damage processing pathway. In support of this notion we
      also observed co-localization of WRN and Ku, particularly after DNA damaging
      treatments.

PMID- 11328877
TI  - Stabilisation of TG- and AG-containing antiparallel DNA triplexes by triplex
      binding ligands.
AB  - We have used DNase I footprinting to examine the interaction of several triplex
      binding ligands with antiparallel TG- and AG-containing triplexes. We find that
      although a 17mer TG-containing oligonucleotide on its own fails to produce a
      footprint at concentrations as high as 30 microM, this interaction can be
      stabilised by several ligands. Within a series of disubstituted
      amidoanthraquinones we find that the 2,7- regioisomer affords the best
      stabilisation of this TG triplex, though the 1,8- isomer also stabilises this
      interaction to some extent. By contrast the 1,5- and 2,6- regioisomers show no
      interaction with TG triplexes. Similar studies with a 13mer AG-containing
      oligonucleotide show the opposite pattern of stabilisation: the 2,6- and 1,5-
      isomers stabilise this triplex, but the 2,7- and 1,8-compounds do not. The
      polycyclic compound BePI strongly stabilises TG- but not AG-containing triplexes,
      while a substituted naphthylquinoline interacts with both antiparallel triplex
      motifs.

PMID- 11328878
TI  - Chromatin structure mapping in Saccharomyces cerevisiae in vivo with DNase I.
AB  - Most methods for assessment of chromatin structure involve chemical or nuclease
      damage to DNA followed by analysis of distribution and susceptibility of cutting
      sites. The agents used generally do not permeate cells, making nuclear isolation
      mandatory. In vivo mapping strategies might allow detection of labile
      constituents and/or structures that are lost when chromatin is swollen in
      isolated nuclei at low ionic strengths. DNase I has been the most widely used
      enzyme to detect chromatin sites where DNA is active in transcription,
      replication or recombination. We have introduced the bovine DNase I gene into
      yeast under control of a galactose-responsive promoter. Expression of the
      nuclease leads to DNA degradation and cell death. Shorter exposure to the active
      enzyme allows mapping of chromatin structure in whole cells without isolation of
      nuclei. The validity and efficacy of the strategy are demonstrated by
      footprinting a labile repressor bound to its operator. Investigation of the inter
      nucleosome linker regions in several types of repressed domains has revealed
      different degrees of protection in cells, relative to isolated nuclei.

PMID- 11328879
TI  - Synthesis and spectroscopic characterization of site-specific 2-amino-1-methyl-6
      phenylimidazo.
AB  - The aim of the present study is to determine the chemical structure and
      conformation of DNA adducts formed by incubation of the bioactive form of 2-amino
      1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), N-acetoxy-PhIP, with a single
      stranded 11mer oligodeoxyribonucleotide. Using conditions optimized to give the
      C8-dG-PhIP adduct as the major product, sufficient material was synthesized for
      NMR solution structure determination. The NMR data indicate that in duplex DNA
      this adduct exists in equilibrium between two different conformational states. In
      the main conformer, the covalently bound PhIP molecule intercalates in the helix,
      whilst in the minor conformation the PhIP ligand is probably solvent exposed. In
      addition to the C8-dG-PhIP adduct, at least eight polar adducts are found after
      reaction of N-acetoxy-PhIP with the oligonucleotide. Three of these were purified
      for further characterization and shown to exhibit lowest energy UV absorption
      bands in the range 342-347 nm, confirming the presence of PhIP or PhIP
      derivative. Accurate mass determination of two of the polar adducts by negative
      ion MALDI-TOF MS revealed ions consistent with a spirobisguanidino-PhIP
      derivative and a ring-opened adduct. The third adduct, which has the same mass as
      the C8-dG-PhIP oligonucleotide adduct, may contain PhIP bound to the N2 position
      of guanine.

PMID- 11328880
TI  - Heat effects on DNA repair after ionising radiation: hyperthermia commonly
      increases the number of non-repaired double-strand breaks and structural
      rearrangements.
AB  - After ionising radiation double-strand breaks (dsb) are lethal if not repaired or
      misrepaired. Cell killing is greatly enhanced by hyperthermia and it is
      questioned here whether heat not only affects dsb repair capacity but also
      fidelity in a chromosomal context. dsb repair experiments were designed so as to
      mainly score non-homologous end joining, while homologous recombination was
      largely precluded. Human male G(0) fibroblasts were either preheated (45 degrees
      C, 20 min) or not before X-irradiation. dsb induction and repair were measured by
      conventional gel electrophoresis and an assay combining restriction digestion
      using a rare cutting enzyme (NotI) and Southern hybridisation, which detects
      large chromosomal rearrangements (>100 kb). dsb induction rate in an X
      chromosomal NotI fragment was 4.8 x 10(-3) dsb/Gy/MB: Similar values were found
      for the genome overall and also when cells were preheated. After 50 Gy,
      fibroblasts were competent to largely restore the original restriction fragment
      size. Five per cent of dsb remained non-rejoined and 14% were misrejoined.
      Correct restitution of restriction fragments occurred preferably during the first
      hour but continued at a slow rate for 12-16 h. In addition, dsb appeared to
      misrejoin throughout the entire repair period. After hyperthermia the fractions
      of non-rejoined and misrejoined dsb were similarly increased to 13 and 51%,
      respectively. It is suggested that heat increases the probability of dsb being
      incorrectly rejoined but it is not likely to interfere with one dsb repair
      pathway in particular.

PMID- 11328882
TI  - Escherichia coli Nth and human hNTH1 DNA glycosylases are involved in removal of
      8-oxoguanine from 8-oxoguanine/guanine mispairs in DNA.
AB  - The spectrum of DNA damage caused by reactive oxygen species includes a wide
      variety of modifications of purine and pyrimidine bases. Among these modified
      bases, 7,8-dihydro-8-oxoguanine (8-oxoG) is an important mutagenic lesion. Base
      excision repair is a critical mechanism for preventing mutations by removing the
      oxidative lesion from the DNA. That the spontaneous mutation frequency of the
      Escherichia coli mutT mutant is much higher than that of the mutM or mutY mutant
      indicates a significant potential for mutation due to 8-oxoG incorporation
      opposite A and G during DNA replication. In fact, the removal of A and G in such
      a situation by MutY protein would fix rather than prevent mutation. This suggests
      the need for differential removal of 8-oxoG when incorporated into DNA, versus
      being generated in situ. In this study we demonstrate that E.coli Nth protein
      (endonuclease III) has an 8-oxoG DNA glycosylase/AP lyase activity which removes
      8-oxoG preferentially from 8-oxoG/G mispairs. The MutM and Nei proteins are also
      capable of removing 8-oxoG from mispairs. The frequency of spontaneous G:C-->C:G
      transversions was significantly increased in E.coli CC103mutMnthnei mutants
      compared with wild-type, mutM, nth, nei, mutMnei, mutMnth and nthnei strains.
      From these results it is concluded that Nth protein, together with the MutM and
      Nei proteins, is involved in the repair of 8-oxoG when it is incorporated
      opposite G. Furthermore, we found that human hNTH1 protein, a homolog of E.coli
      Nth protein, has similar DNA glycosylase/AP lyase activity that removes 8-oxoG
      from 8-oxoG/G mispairs.

PMID- 11328881
TI  - Repair of hydantoins, one electron oxidation product of 8-oxoguanine, by DNA
      glycosylases of Escherichia coli.
AB  - 8-oxoguanine (8-oxoG), induced by reactive oxygen species and arguably one of the
      most important mutagenic DNA lesions, is prone to further oxidation. Its one
      electron oxidation products include potentially mutagenic guanidinohydantoin (Gh)
      and spiroiminodihydantoin (Sp) because of their mispairing with A or G. All three
      oxidized base-specific DNA glycosylases of Escherichia coli, namely endonuclease
      III (Nth), 8-oxoG-DNA glycosylase (MutM) and endonuclease VIII (Nei), excise Gh
      and Sp, when paired with C or G in DNA, although Nth is less active than the
      other two. MutM prefers Sp and Gh paired with C (kcat/K(m) of 0.24-0.26 min(-1) x
      nM(-1)), while Nei prefers G over C as the complementary base (k(cat)/K(m) - 0.15
      0.17 min(-1) x nM(-1)). However, only Nei efficiently excises these paired with
      A. MutY, a 8-oxoG.A(G)-specific A(G)-DNA glycosylase, is inactive with Gh(Sp).A/G
      containing duplex oligonucleotide, in spite of specific affinity. It inhibits
      excision of lesions by MutM from the Gh.G or Sp.G pair, but not from Gh.C and
      Sp.C pairs. In contrast, MutY does not significantly inhibit Nei for any Gh(Sp)
      base pair. These results suggest a protective function for MutY in preventing
      mutation as a result of A (G) incorporation opposite Gh(Sp) during DNA
      replication.

PMID- 11328883
TI  - Condensation by DNA looping facilitates transfer of large DNA molecules into
      mammalian cells.
AB  - Experimental studies of complete mammalian genes and other genetic domains are
      impeded by the difficulty of introducing large DNA molecules into cells in
      culture. Previously we have shown that GST-Z2, a protein that contains three zinc
      fingers and a proline-rich multimerization domain from the polydactyl zinc finger
      protein RIP60 fused to glutathione S-transferase (GST), mediates DNA binding and
      looping in vitro. Atomic force microscopy showed that GST-Z2 is able to condense
      130-150 kb bacterial artificial chromosomes (BACs) into protein-DNA complexes
      containing multiple DNA loops. Condensation of the DNA loops onto the Z2 protein
      BAC DNA core complexes with cationic lipid resulted in particles that were
      readily transferred into multiple cell types in culture. Transfer of total
      genomic linear DNA containing amplified DHFR genes into DHFR(-) cells by GST-Z2
      resulted in a 10-fold higher transformation rate than calcium phosphate co
      precipitation. Chinese hamster ovarian cells transfected with a BAC containing
      the human TP53 gene locus expressed p53, showing native promoter elements are
      active after GST-Z2-mediated gene transfer. Because DNA condensation by GST-Z2
      does not require the introduction of specific recognition sequences into the DNA
      substrate, condensation by the Z2 domain of RIP60 may be used in conjunction with
      a variety of other agents to provide a flexible and efficient non-viral platform
      for the delivery of large genes into mammalian cells.

PMID- 11328884
TI  - Binding to the naturally occurring double p53 binding site of the Mdm2 promoter
      alleviates the requirement for p53 C-terminal activation.
AB  - Genotoxic stress activation of the tumor suppressor transcription factor p53
      involves post-translational C-terminal modifications that increase both protein
      stability and DNA binding activity. We compared the requirement for p53 protein
      activation of p53 target sequences in two major p53-regulated genes, p21/WAF1
      (encoding a cell cycle inhibitory protein) and Mdm2 (encoding a ubiquitin ligase
      that targets p53 for proteolytic degradation). The p53 binding site in the
      proximal p21/WAF1 promoter contains a single p53 binding consensus sequence,
      while the p53 binding site in the Mdm2 promoter contains two consensus sequences
      linked by a 17 bp spacer. Binding of recombinant p53 protein to the p21/WAF1
      binding site required monoclonal antibody PAb421, which can mimic activating
      phosphorylation and/or acetylation events at the C-terminus. In contrast,
      recombinant p53 bound strongly to the Mdm2 binding site in the absence of PAb421
      antibody. Separate binding to each consensus sequence of the Mdm2 binding site
      still required PAb421, indicating that p53 binding was not simply due to greater
      affinity to the Mdm2 consensus sequences. Linking two p21/WAF1 binding sites with
      the 17 bp spacer region from the Mdm2 gene eliminated the PAb421 requirement for
      p53 binding to the p21/WAF1 site. These results suggest a mechanism for
      regulation of Mdm2 gene transcription that differs from that other p53-induced
      genes by its lack of a requirement for C-terminal activation of p53 protein. A
      steady induction of Mdm2 protein would maintain p53 protein at low levels until
      post-translational modifications following DNA damage increased p53 activity
      towards other genes, mediating p53 growth inhibitory and apoptotic activities.

PMID- 11328885
TI  - Translesional synthesis on a DNA template containing N2-methyl-2'-deoxyguanosine
      catalyzed by the Klenow fragment of Escherichia coli DNA polymerase I.
AB  - Formaldehyde is produced in most living systems and is present in the
      environment. Evidence that formaldehyde causes cancer in experimental animals
      infers that it may be a carcinogenic hazard to humans. Formaldehyde reacts with
      the exocyclic amino group of deoxyguanosine, resulting in the formation of N2
      methyl-2'-deoxyguanosine (N2-Me-dG) via reduction of the Schiff base. The same
      reaction is likely to occur in living cells, because cells contain endogenous
      reductants such as ascorbic acid and gluthathione. To explore the miscoding
      properties of formaldehyde-derived DNA adducts a site-specifically modified
      oligodeoxynucleotide containing a N2-Me-dG was prepared and used as the template
      in primer extension reactions catalyzed by the Klenow fragment of Escherichia
      coli DNA polymerase I. The primer extension reaction was slightly stalled one
      base before the N2-Me-dG lesion, but DNA synthesis past this lesion was readily
      completed. The fully extended products were analyzed to quantify the miscoding
      specificities of N2-Me-dG. Preferential incorporation of dCMP, the correct base,
      opposite the lesion was observed, along with small amounts of misincorporation of
      dTMP (9.4%). No deletions were detected. Steady-state kinetic studies indicated
      that the frequency of nucleotide insertion for dTMP was only 1.2 times lower than
      for dCMP and the frequency of chain extension from the 3'-terminus of a dT:N2-Me
      dG pair was only 2.1 times lower than from a dC:N2-Me-dG pair. We conclude that
      N2-Me-dG is a miscoding lesion capable of generating G-->A transition mutations.

PMID- 11328887
TI  - Life and death in the kidney: prospects for future therapy.

PMID- 11328886
TI  - A new mathematical model for relative quantification in real-time RT-PCR.
AB  - Use of the real-time polymerase chain reaction (PCR) to amplify cDNA products
      reverse transcribed from mRNA is on the way to becoming a routine tool in
      molecular biology to study low abundance gene expression. Real-time PCR is easy
      to perform, provides the necessary accuracy and produces reliable as well as
      rapid quantification results. But accurate quantification of nucleic acids
      requires a reproducible methodology and an adequate mathematical model for data
      analysis. This study enters into the particular topics of the relative
      quantification in real-time RT-PCR of a target gene transcript in comparison to a
      reference gene transcript. Therefore, a new mathematical model is presented. The
      relative expression ratio is calculated only from the real-time PCR efficiencies
      and the crossing point deviation of an unknown sample versus a control. This
      model needs no calibration curve. Control levels were included in the model to
      standardise each reaction run with respect to RNA integrity, sample loading and
      inter-PCR variations. High accuracy and reproducibility (<2.5% variation) were
      reached in LightCycler PCR using the established mathematical model.

PMID- 11328888
TI  - Permeability plasma factors in nephrotic syndrome: more than one factor, more
      than one inhibitor.

PMID- 11328889
TI  - Modulation of the renin-angiotensin system in proteinuric renal disease: are
      there added benefits?

PMID- 11328890
TI  - Hormone replacement therapy and blood pressure in normotensive and hypertensive
      women.

PMID- 11328891
TI  - When should we start erythropoietin therapy?

PMID- 11328892
TI  - Islet transplantation: a field on the move.

PMID- 11328893
TI  - HLA-specific alloantibodies and renal graft outcome.
AB  - HLA-specific humoral immunity, as a result of recipient allosensitization,
      induces hyperacute rejection of allogenic kidney grafts. Cross-match tests are
      performed to avoid this complication. However, current techniques do not allow
      determination of HLA-specificity of donor-reactive antibodies in the acute
      cadaver-donor situation. New methods are described and discussed in this report
      as well as the alloantibody specificities that are of clinical importance.
      Alloantibodies not only mediate hyperacute rejection but may also participate in
      the acute rejection of organ grafts. Clinical associations between early
      immunological complications, such as acute rejection, in heart, liver and kidney
      allografted patients and pre-transplantation humoral alloimmunity emphasize the
      need for proper determination of donor-specific humoral immunity prior to
      transplantation.

PMID- 11328894
TI  - The un-physiology of peritoneal dialysis solution and the peritoneal membrane:
      from basic research to clinical nephrology.

PMID- 11328895
TI  - Monocyte/mesangial cell interactions in high-glucose co-cultures.
AB  - BACKGROUND: Monocytes bind to human mesangial cells (HMC) in a co-culture model
      of leukocyte/ glomerular cell interactions. Since monocytic infiltration has been
      demonstrated in the early stages of diabetic glomerulopathy, we examined whether
      co-culture with myelomonocytes of the U937 cell line in media mimicking the
      diabetic microenvironment modulated phenotype, growth, and extracellular matrix
      production patterns of HMC. METHODS: HMC monolayers grown for 5 days in 5.5
      mmol/l (NG) or 30 mmol/l (HG) glucose media were examined 3, 24 and 48 h after
      addition of U937 cells by computer-assisted image analysis/fluorescence
      microscopy following fixation, staining for cell adhesion, and TUNEL/propidium
      iodide labelling for apoptosis. As matrix components may be relevant to both
      phenotype of cultured HMC and monocyte adhesion, reverse transcription-polymerase
      chain reaction, zymography, and ELISA were used to detect urokinase-plasminogen
      activator (uPa), collagen type IV (COL IV), transforming growth factor beta1 (TGF
      beta1), matrix metalloproteinases (MMP), and relative inhibitors (tissue
      inhibitor of MMP (TIMP)) expression in co-cultures in NG/HG. RESULTS: U937
      adhesion at 1-3 h was increased in HG (from 54.9+/-6.6 to 87.1+/-5.8% U937/HMC).
      Control HMC proliferating in NG supplemented with 10% fetal bovine serum had an
      average cross-sectional area of 9993+/-505 micro(2) with 1.2+/-0.1 hillocks/high
      power field, which increased to 13 651+/- 1114 micro(2) with 0.5+/-0.2
      hillocks/high-power field in HG (P<0.05). TUNEL+HMC were nearly identical (4.9+/
      1.7 vs 4.2+/-0.4% in HG, P=NS). Enhanced transcription and secretion of urokinase
      (uPA, +656%), COL IV (+137%), TGF-beta1 (+590%) were observed in co-cultures in
      HG. COL IV and TGF-beta1, but not uPA, were also increased in HMC alone, exposed
      to HG for 5 days. MMP-2/TIMP-2 ratio was decreased while MMP-1/TIMP-1 was
      increased in HG co-cultures. In both NG and HG, U937 adhesion reduced HMC number
      and hillocks at 24 h, with constant apoptosis. The effects of U937 were no longer
      detectable at 48 h, when apoptosis was 2.1+/-0.6 vs 4.0+/-0.4% in HG, and cell
      counts returned above basal, possibly due to a delayed proliferative response.
      CONCLUSIONS: High glucose medium increases U937 cell adhesion to HMC. In turn,
      monocytes modulate number and spatial distribution of HMC, which are also
      markedly affected by ambient glucose levels. These interactions may be relevant
      to leukocyte infiltration, mesangial expansion, and glomerulosclerosis in
      diabetes.

PMID- 11328896
TI  - Rapid and diverse changes of gene expression in the kidneys of protein-overload
      proteinuria mice detected by microarray analysis.
AB  - BACKGROUND: Microarray is a method that allows the analysis of a large number of
      genes at the same time. We applied this method to show the difference of gene
      expression in the kidney caused by proteinuria. METHODS: An experimental mouse
      model of protein overload was prepared by bovine serum albumin injection. The
      mRNAs of kidneys isolated after 0, 1, 2, 3 and 4 weeks loading were analysed by
      Northern blotting. We analysed about 18000 genes by microarray. The expression
      patterns of the microarray were displayed on control, 1 and 3 weeks of protein
      overload using the clustering procedure. A clone showing the greatest changes of
      up-regulation in the kidney was cloned and analysed by in situ hybridization and
      immunohistochemistry. RESULTS: Over 1600 kinds of gene expression were confirmed
      in control kidneys. Proteinuria caused systematic changes of gene expression
      demonstrated by the cluster analysis. The up-regulation of osteopontin mRNA was
      shown and confirmed by Northern blot analysis. One of the clones showing the
      largest changes, AA275245, was isolated and characterized. It revealed that
      AA275245 was an unreported 3' non-coding region of vinculin mRNA which was
      associated with cytoskeleton proteins (e.g. alpha-actinin, talin, F-actin).
      Immunohistochemistry and in situ hybridization showed that this clone was
      identified in glomeruli as a mesangial pattern. The detected signal intensity
      using both methods, however, was virtually identical in control and disease
      kidney models. All data including images and analysed signal intensities are
      accessible on the web site. CONCLUSION: The microarray analysis revealed that the
      renal gene expression pattern was changed dynamically in mice with experimentally
      induced proteinuria within a few weeks.

PMID- 11328897
TI  - Erythropoietin enhances recovery after cisplatin-induced acute renal failure in
      the rat.
AB  - BACKGROUND: Erythropoietin (Epo) is a growth factor whose synthesis mainly takes
      place in the kidney. Epo has been shown to support the growth not only of
      erythroid progenitor cells but also of certain other cell types. We attempted to
      establish whether Epo enhances the recovery from acute renal failure induced by
      cisplatin. METHODS: Sprague-Dawley rats were randomized into three groups. In the
      cisplatin group, animals received one intraperitoneal injection of cisplatin (6
      mg/kg) and a daily injection of placebo for 9 days. In the cisplatin+Epo group,
      animals received intrapertoneal cisplatin and a daily injection of Epo (100
      IU/kg) for 9 days. In the control group, animals received both placebo
      preparations alone. Para-aminohippuric acid and inulin clearances were determined
      after 4 and 9 days to evaluate renal blood flow and glomerular filtration rate.
      In addition, light microscopy and immunohistochemistry examinations were
      performed, and in situ proliferating cell nuclear antigen (PCNA) staining was
      done to estimate the degree of renal tubular cell regenerative activity. The
      potential role of epithelial growth factor (EGF) was evaluated by semi
      quantitative assessment of EGF immunostaining. RESULTS: Renal blood flow and
      glomerular filtration rate decreased significantly in cisplatin and cisplatin+Epo
      groups versus control group at day 4. However, at day 9, they both were
      significantly greater in cisplatin+Epo-treated animals than in rats that had
      received cisplatin alone. Tubular cell regeneration was significantly enhanced at
      day 4 in cisplatin+Epo group, compared with cisplatin and control groups
      respectively. EGF immunostaining was not significantly different between the
      three groups. CONCLUSION: Epo significantly enhanced the rate of recovery from
      acute renal failure induced by cisplatin. PCNA staining indicated that Epo might
      act directly via stimulation of tubular cell regeneration.

PMID- 11328898
TI  - Identification of mutations including de novo mutations in Korean patients with
      hypokalaemic periodic paralysis.
AB  - BACKGROUND: Hypokalaemic periodic paralysis (hypoPP) is an autosomal dominant
      disorder involving the abnormal function of ion channels and it is characterized
      by paralysis attacks of varying severity, accompanied by a fall in blood
      potassium levels. Linkage analysis showed that the candidate locus responsible
      for hypoPP was localized to chromosome 1q31-32, and this locus encoded the muscle
      dihydropyridine-sensitive calcium channel alpha(1)-subunit (CACNA1S). So far,
      three different mutations in CACNA1S gene have been identified in patients with
      hypoPP: Arg528His, Arg1239His and Arg1239Gly in Caucasian patients. However,
      there are few reports about the mutations of CACNA1S gene in other races.
      METHODS: In this study, four Korean families with five hypoPP patients were
      screened for mutations of CACNA1S gene with polymerase chain reaction-based
      restriction analysis and single-strand conformation polymorphism analysis. To
      determine the mode of inheritance, haplotype analysis was done with three
      microsatellite markers (D1S1726, CACNL1A3, and D1S1723). RESULTS: Arg528His
      mutation was detected in three families, and one family had no known mutations.
      Moreover, for the first time, we detected de novo Arg528His mutations in two out
      of three families with hypoPP. Haplotype analysis using three microsatellite
      markers (D1S1726, CACNL1A3, and D1S1723) suggested the occurrence of de novo
      Arg528His mutations in two of the three families with Arg528His mutation.
      CONCLUSIONS: Arg528His mutations of CACNA1S, including de novo Arg528His
      mutations, were found in Korean patients with hypoPP. These results imply that de
      novo mutation, in addition to non-penetrance, is one of the genetic mechanisms
      that can explain the previous clinical observation that hypoPP occurs
      sporadically without family history.

PMID- 11328899
TI  - Distribution of alpha-chains of type IV collagen in glomerular basement membranes
      with ultrastructural alterations suggestive of Alport syndrome.
AB  - BACKGROUND: In Alport syndrome (AS) impaired production and/or assembly of col IV
      alpha-chain isoforms results in abnormal structure of glomerular basement
      membrane (GBM), haematuria and, frequently, progressive renal disease. We
      investigated the relationship between col IV alpha-chains expression and
      morphology of GBM, as a possible key to the better understanding of the
      pathogenesis of renal disease in AS. METHODS: GBM distribution of col IV alpha1-,
      alpha3-, and alpha5-chain was investigated by immunohistochemistry in 32 patients
      (21 males and 11 females, mean age at biopsy of 11.5 years) with ultrastructural
      findings suggestive of AS. Ten patients had a proven COL4A5 mutation. Based on
      the severity of ultrastructural findings, the biopsies were grouped in three (I
      III) electron microscopy (EM) classes. Significant EM changes of GBM (thinning,
      thickening, splitting, basket weaving of the lamina densa) were singularly
      evaluated using a semiquantitative scale (0-3). RESULTS: Col IV alpha1-chain was
      demonstrated in GBM of all patients. Three patterns of staining for col IValpha3-
      and alpha5-chains were observed: positive, negative, and alpha3(IV)
      positive/alpha5(IV)-negative. By chi(2)-test, EM class III lesions and complete
      loss of alpha3(IV)- and alpha5(IV)-antigen were significantly more frequent
      (P<0.05 and P<0.01) in male patients, but no significant relation was observed
      between EM classes and immunohistochemical patterns. GBM alterations did not
      correlate with staining for alpha5(IV)-chain. Intensity of alpha3(IV)-chain
      staining, however, had a negative correlation (P<0.05) with the severity of GBM
      basket weaving. CONCLUSIONS: Our results suggest that the alpha3(IV)-chain
      containing col IV-network plays a fundamental role in structural and, possibly,
      functional organization of GBM. Absence of alpha3(IV)-chain in GBM could indicate
      a more severe renal disease in AS.

PMID- 11328900
TI  - Renal histopathology and clinical course in 94 patients with Wegener's
      granulomatosis.
AB  - BACKGROUND: The main purpose of this study was to examine histopathological
      changes seen in renal biopsies from patients with Wegener's granulomatosis (WG)
      with varying degrees of renal involvement and to study possible correlations
      between the morphological variables and the severity of the disease. METHODS:
      Ninety-four patients with WG and active renal disease were included in this
      retrospective study. All patients had a percutaneous renal biopsy taken on their
      first admission to the hospital and 14 patients had a second biopsy. The patients
      were followed for a median of 42.5 months (range 0.5-184). RESULTS: Segmental
      necrotizing glomerulonephritis and extracapillary proliferation were present in
      85.1 and 91.5% respectively. Of seven patients (7.4%) with normal serum
      creatinine and urinary protein excretion <0.5 g/day, all had crescents and six
      had segmental glomerular necrosis. Serum creatinine at biopsy correlated
      significantly with the percentage of glomeruli with crescents (rho=0.52,
      P=0.0004), with necrosis (rho=0.36, P=0.002) and with the percentage of normal
      glomeruli (rho=-0.55, P=0.0003). On a multivariate analysis, only the percentage
      of normal glomeruli was significantly associated with renal function and
      development of end-stage renal disease. In 14 second biopsies after a mean of
      41.2 (+/-26) months, chronicity scores had increased significantly in 13 biopsies
      in spite of full immunosuppressive treatment. CONCLUSION: Although renal biopsy
      is of value in defining renal involvement in WG, it is of limited help in the
      early stage of the disease in predicting renal outcome for the individual
      patient. A follow-up biopsy can be useful in revealing the degree of activity and
      chronicity and hence be of importance for the choice of further therapy.

PMID- 11328901
TI  - Effect of Lisinopril on the progression of renal insufficiency in mild
      proteinuric non-diabetic nephropathies.
AB  - BACKGROUND: The aim of the study was to determine whether Lisinopril, an ACE
      inhibitor (ACEi), was more effective than other antihypertensive agents in
      slowing the progression of non-diabetic chronic renal diseases in patients with
      baseline proteinuria < or =1.0 g/day. METHODS: In an open, multicentre study all
      eligible patients entered a 3 months run-in phase during which antihypertensive
      therapy (with exclusion of ACEi) was adjusted in order to obtain a supine
      diastolic blood pressure < or =90 mmHg and urinary protein excretion and renal
      function stability were verified. One hundred and thirty-one patients with
      chronic renal insufficiency (Clcr between 20-50 ml/min) because of primary
      renoparenchymal diseases and proteinuria < or =1.0 g/day, were randomized to
      Lisinopril (L=66) or alternative antihypertensive therapy (C=65). Changes in
      renal function were assessed by inulin (Clin) clearance. RESULTS: During the
      follow-up period of 22.5+/-5.6 months, Clin did not change significantly in group
      L (-1.31+/-0.6 ml/min/1.73 m(2)) differing significantly from group C in which it
      declined markedly (-6.71+/-3.6 ml/min/1.73 m(2)) (P<0.04). Seven patients
      experienced adverse events that prompted discontinuation of treatment: four in
      group L and three in group C; in addition seven patients showed severe
      deterioration in renal function requiring dialysis: two in group L and five in
      group C. The overall risk of the combined end-points: need for dialysis or
      halving of GFR was significantly higher in group C versus group L. During the
      study the mean value for systolic blood pressure was 137.8+/-14.6 SD mmHg in
      group L and 140.8+/-14.1 SD mmHg in group C; the mean difference between groups,
      during and at the end of the study, was 2 mmHg (NS). The mean diastolic blood
      pressure during the study was 83.8+/-8.6 SD mmHg in group L and 84.3+/-7.56 SD
      mmHg in group C; during and at the end of the study the mean diastolic difference
      between groups was 1 mmHG: CONCLUSION: This study, employing a sensitive
      measurement of renal function and with similar blood pressure in both groups,
      provides support to the hypothesis that ACEi have a specific renoprotective
      effect, in addition to blood pressure control, also in patients with mild
      proteinuria.

PMID- 11328902
TI  - A randomized study of oral vs intravenous iron supplementation in patients with
      progressive renal insufficiency treated with erythropoietin.
AB  - BACKGROUND: Correction of anaemia as a result of renal failure improves
      cardiovascular function and also provides significant cognitive and emotional
      benefits. The most appropriate route for iron supplementation has not been
      determined for patients with chronic renal failure who are not yet on dialysis.
      METHODS: Forty-five anaemic patients with progressive renal insufficiency (PRI)
      were prospectively randomized to receive oral (ferrous sulphate 200 mg tds) or
      intravenous (300 mg iron sucrose monthly) iron treatment. Erythropoietin (rHuEpo)
      was simultaneously commenced and the dose adjusted according to a pre-established
      protocol. RESULTS: There were no significant differences in baseline patient
      characteristics between the two groups. The average follow-up was 5.2 months.
      Three patients suffered possible allergic reactions to iron sucrose. Haemoglobin
      response and changes in red cell hypochromasia were similar in the two groups,
      but serum ferritin was significantly higher in the intravenous group. The
      starting dose of rHuEpo could be temporarily discontinued in 43% of patients on
      oral iron and 33% of patients receiving iron sucrose (NS). rHuEpo was increased
      after 3 months in 9% of patients on oral iron and 19% of patients receiving iron
      sucrose (NS). Final doses of rHuEpo were 33.5 (0-66) and 41.6 (0-124) U/kg/week
      respectively in the oral and intravenous groups (NS). Although gastro-intestinal
      symptoms were more commonly reported in patients taking oral iron, these were
      mild according to scores on visual analogue scales. Dietary protein and energy
      intake were not significantly different in the two groups at 0, 3 and 6 months.
      CONCLUSIONS: In pre-dialysis patients, the efficacy of monthly 300 mg iron
      sucrose given intravenously is not superior with regard to haemoglobin response
      and rHuEpo dose as compared with a daily oral dose of 600 mg of ferrous sulphate
      or equivalent. Where intravenous iron is preferred, lower doses may help to
      reduce the incidence of allergic or "free iron" reactions, especially in patients
      with low body mass.

PMID- 11328903
TI  - Procalcitonin for accurate detection of infection in haemodialysis.
AB  - BACKGROUND: Infection results in considerable morbidity and mortality in
      haemodialysis patients. Diagnosis of infection can be difficult because currently
      applied laboratory parameters may be non-specifically altered due to uraemia or
      haemodialysis (HD). This study investigated the diagnostic value and kinetics of
      serum procalcitonin (PCT), a low-molecular-weight protein, in patients receiving
      intermittent HD. METHODS: Sixty-eight patients receiving intermittent HD for end
      stage renal disease (n=48) or acute renal failure (n=20) were prospectively
      studied, 47 treated with high-flux and 21 with low-flux membranes. Of 36 patients
      with severe infections or sepsis, 27 were treated with high-flux and nine with
      low-flux membranes. WBC, serum PCT and C-reactive protein (CRP) concentrations
      were measured immediately before HD, and PCT repeatedly during the following 48
      h. RESULTS: When determined immediately before HD, PCT demonstrated a sensitivity
      of 89%, a specificity of 81%, and positive and negative predictive values of 84
      and 87%, indicating severe infection or sepsis. These levels were higher than the
      respective values for CRP (89, 48, 68 and 78%) and WBC (58, 75, 71 and 59%).
      After 4 h of HD with high-flux membranes, PCT decreased significantly to 83+/-25%
      and did not return to predialysis concentrations before 48 h. This decrease in
      serum PCT resulted in markedly reduced sensitivity (65%) and negative predictive
      value (54%). In contrast, no marked change in PCT concentration occurred during
      or after HD with low-flux membranes. CONCLUSION: Serum PCT is an accurate
      indicator of severe infection and sepsis in patients receiving intermittent HD.
      High-flux membranes substantially decrease PCT. When utilizing high flux
      membranes, serum PCT concentrations should be determined prior to the start of
      HD.

PMID- 11328904
TI  - Procalcitonin: a new marker of inflammation in haemodialysis patients?
AB  - BACKGROUND: Although procalcitonin (PCT) has been described as a new marker of
      infection and inflammation, it has not been extensively studied in dialysis
      patients. METHODS: We measured plasma PCT levels in 62 patients on maintenance
      haemodialysis (30 M/32 F, age 61.8+/-17.1 years, on dialysis for 75+/-93 months,
      12 h/week, with a Kt/V of 1.53+/-0.31, high-flux membrane being used in 25
      patients and low-flux in 37 patients, without reuse). PCT levels were compared
      with other markers of inflammation and nutritional status, including C-reactive
      protein (CRP), fibrinogen, interleukin-6 (IL-6), leukocytes, urea, creatinine,
      albumin, prealbumin, normalized protein catabolic rate (nPCR), haemoglobin (Hb),
      and epoetin (Epo) doses. Patients were divided into different groups according to
      their infectious and vascular status. RESULTS: PCT plasma levels before dialysis
      were 0.69+/-0.81 ng/ml. Fifty-seven per cent of PCT values were higher than the
      upper normal limit of 0.5 ng/ml. CRP and PCT concentrations were high in patients
      with a current infection, while IL-6 values were elevated in all patients
      regardless of infection status. Plasma CRP concentrations before dialysis were
      21.2+/-31.4 mg/l, and 70% of these values were higher than the upper normal
      limit. CRP, PCT, IL-6, and fibrinogen were positively correlated with each other
      and were all negatively correlated with albumin. Prealbumin was negatively
      correlated with CRP and IL-6. In the 43 patients treated with Epo, haemoglobin
      was negatively correlated with IL-6 and Epo doses, while Epo doses were
      positively correlated with IL-6 but not with CRP or PCT. The 23 patients with
      both elevated PCT and CRP plasma levels had the lowest Hb, albumin, and
      prealbumin concentrations, and the highest fibrinogen concentrations and Epo
      doses. CONCLUSION: PCT in haemodialysis patients is positively correlated with
      currently used markers of inflammation such as CRP and fibrinogen, and negatively
      correlated with markers of nutritional status such as albumin. The concomitant
      elevations in PCT and CRP could be more sensitive in the evaluation of
      inflammation than each marker separately.

PMID- 11328905
TI  - Anticoagulation intensity sufficient for haemodialysis does not prevent
      activation of coagulation and platelets.
AB  - BACKGROUND: A single bolus of dalteparin at the start of haemodialysis (HD) may
      prevent clot formation, but subclinical activation of platelets and coagulation
      may still occur. Consequently, the relationship between clinical clotting events
      and activation markers of platelets and coagulation before and during HD is of
      interest. METHODS: The effect of tapered doses of dalteparin during 84 HD
      sessions (4-4.5 h) was prospectively examined in 12 patients. Six of the patients
      were treated with warfarin. The initial dalteparin dose was reduced to 50% if no
      clotting was observed. Clinical clotting was evaluated by inspection of the air
      trap every hour and by inspection of the dialyser after each session. Anti-FXa
      activity was measured for assessment of dalteparin activity. Markers of activated
      plasma coagulation, (thrombin-antithrombin (TAT) and prothrombin fragment 1+2
      (PF1+2)) and a marker of platelet activation (beta-thromboglobulin, beta-TG),
      were measured before the start of and after 3 and 4 h of dialysis. Ten pre
      dialytic patients with chronic renal failure served as a control group. A total
      of 230 measurements of each parameter were performed. RESULTS: An anti-FXa
      activity above 0.4 IU/ml at the end of HD inhibits overt clot formation for 4 h.
      This was obtained by an intravenous dalteparin dose of about 5000 IU. TAT and
      PF1+2 correlated to clinical clotting episodes (r=0.50 and 0.47, P<0.001). beta
      TG was not significantly correlated to clinical clotting. All parameters
      increased during the sessions (TAT, PF1+2, beta-TG, P<0.001). When measurements
      during clinical clotting episodes were disregarded, all parameters were still
      markedly increased. Warfarin-treated patients had lower TAT and PF1+2. Dialysis
      patients had higher beta-TG values than pre-dialytic patients. CONCLUSION:
      Despite clinically effective anticoagulation, obtained by dalteparin
      administration, platelets and coagulation are activated by HD, resulting in a
      potentially thrombophilic state. Warfarin treatment reduces clinical clot
      formation and subclinical activation of coagulation.

PMID- 11328906
TI  - Effect of ultrafiltration on peripheral urea sequestration in haemodialysis
      patients.
AB  - BACKGROUND: Ultrafiltration (UF) is assumed to enhance urea removal during
      haemodialysis (HD) because of convective transport and because of contraction of
      urea distribution volume. However, UF-induced blood volume reduction has been
      hypothesized to enhance peripheral urea sequestration and post-dialysis urea
      rebound (PDUR), possibly reducing HD effectiveness. The effect of UF on PDUR was
      investigated in this study. METHODS: Nine HD patients were studied on two
      subsequent treatment days. The first HD was performed with UF (UF-rate=0.78+/
      0.27 l/h), and the second treatment without UF. Serial measurements of serum
      water urea nitrogen concentration, arterial blood pressures (BP), and relative
      blood volume changes (BV%) were obtained over the duration of HD. RESULTS: BP and
      BV% decreased with UF (BP(sys)= -9%, BP(dia)=-8%, BP(mean)=-9%, BV%=-15%) but
      increased or remained unchanged without UF (BP(sys)= 9%, BP(dia)=12%,
      BP(mean)=11%, BV%=1%). PDUR was 28.6+/-9.6% without UF, and increased in every
      single patient with UF (40.7+/-13.2%, P<0.01). Modelled perfusion of the
      peripheral low-flow compartment decreased from 1.45+/-0.54 l/min without UF to
      0.91+/-42 l/min with UF (P<0.05), thereby explaining an enhanced two-compartment
      effect and increasing PDUR. CONCLUSION: The significant increase in the two
      compartment effect of urea kinetics observed in current HD accompanied by UF can
      be explained by compensatory, intradialytic blood flow redistribution induced by
      blood volume reduction. Because of the link between UF and blood flow, limited
      solute clearance treatment modes that optimize fluid removal such as variable UF
      will also have favourable effects on delivered dose of dialysis.

PMID- 11328907
TI  - Influence of dialysis modalities on serum AGE levels in end-stage renal disease
      patients.
AB  - BACKGROUND: The accumulation of advanced glycation end-products (AGEs) in end
      stage renal disease (ESRD) influenced by dialysis modalities is of current
      interest. Highly permeable membranes in haemodialysis or haemofiltration should
      be able to eliminate circulating AGEs as well as their AGE precursors more
      efficiently. METHODS: In our study, 10 non-diabetic and 10 diabetic ESRD patients
      were on haemodialysis with low-flux membranes (LF) followed by a cross-over
      haemodialysis with high-flux or super-flux polysulfone membranes (HF, SF) for 6
      months each. We measured the protein-bound pentosidine and free pentosidine serum
      levels by high-performance liquid chromatography (HPLC) as well as the serum AGE
      peptide, AGE-beta(2)-microglobulin and beta(2)-microglobulin concentrations,
      using ELISA assays. RESULTS: All parameters investigated were significantly
      higher in dialysis patients than in healthy subjects. The reduction rates during
      a single dialysis session were found to be higher using the SF than those
      obtained with the HF (free pentosidine 82.4+/-7.3 vs 76.6+/- 8.7%; AGE peptides
      79.7+/-7.7 vs 62.3+/-14.7%; AGE-beta(2)-microglobulin 64.0+/-16.5 vs 45.4+/
      17.7%; beta(2)-microglobulin 70.5+/-5.6 vs 58.2+/-6.0%). The protein-bound
      pentosidine levels remained constant over the respective dialysis sessions. In
      the 6-month treatment period with the SF, decreased pre-dialysis serum levels of
      protein-bound pentosidine, free pentosidine and AGE peptides were observed in non
      diabetics and diabetics as compared with values obtained with the LF. The
      respective pre-dialysis AGE-beta(2)-microglobulin concentrations decreased
      insignificantly, whereas those of beta(2)-microglobulin were significantly lower.
      Using the HF dialyser, only moderate changes of the parameters measured were
      noted. CONCLUSION: Treatment with the biocompatible polysulfone SF dialyser seems
      to be better suited to lower serum AGE levels and to eliminate their precursors.

PMID- 11328908
TI  - Effect of calcitriol treatment and withdrawal on hyperparathyroidism in
      haemodialysis patients with hypocalcaemia.
AB  - BACKGROUND: Calcitriol is used to treat secondary hyperparathyroidism in dialysis
      patients. For similarly elevated parathyroid hormone (PTH) levels, the PTH
      response to calcitriol treatment is believed to be better in hypocalcaemic
      dialysis patients than in dialysis patients with higher serum calcium values.
      Furthermore, few studies have evaluated the rapidity of the rebound in serum PTH
      values after prolonged treatment with calcitriol. Our goal was to evaluate (i)
      the PTH response to calcitriol treatment in hypocalcaemic haemodialysis patients,
      (ii) the rapidity of rebound in PTH after calcitriol treatment was stopped, and
      (iii) whether the effect of calcitriol treatment on PTH levels could be separated
      from those produced by changes in serum calcium and phosphate values. METHODS:
      Eight haemodialysis patients (29+/-3 years) with hypocalcaemia and
      hyperparathyroidism were treated thrice weekly with 2 microg of intravenous
      calcitriol and were dialysed with a 3.5 mEq/l calcium dialysate. Parathyroid
      function (PTH-calcium curve) was determined before and after 30 weeks of
      calcitriol treatment and 15 weeks after calcitriol treatment was stopped.
      RESULTS: Pretreatment PTH and ionized calcium values were 907+/-127 pg/ml and
      3.89+/-0.12 mg/dl (normal, 4.52+/-0.07 mg/dl). During calcitriol treatment, one
      patient did not respond, but basal (predialysis) PTH values in the other seven
      patients decreased from 846+/-129 to 72+/-12 pg/ml, P<0.001 and in all seven
      patients, the decrease exceeded 85%. During the 15 weeks after calcitriol
      treatment was stopped, a slow rebound in basal PTH values in the seven patients
      was observed, 72+/-12 to 375+/-44 pg/ml. Covariance analysis was used to evaluate
      the three tests of parathyroid function (0, 30, and 45 weeks), and showed that
      calcitriol treatment was associated with reductions in maximal PTH values while
      reductions in basal PTH were affected by ionized calcium and serum phosphate. The
      basal/maximal PTH ratio and the set point of calcium were associated with changes
      in ionized calcium. CONCLUSIONS: In haemodialysis patients with hypocalcaemia,
      (i) moderate to severe hyperparathyroidism responded well to treatment with
      calcitriol, (ii) reductions in maximal PTH were calcitriol dependent while
      reductions in basal PTH were affected by the ionized calcium and serum phosphate
      concentrations, (iii) changes in the basal/maximal PTH ratio and the set point of
      calcium were calcium dependent, and (iv) the delayed rebound in basal PTH levels
      after withdrawal of calcitriol treatment may have been due to the long duration
      of treatment and the marked PTH suppression during treatment.

PMID- 11328909
TI  - The tolerance and efficacy of interferon-alpha in haemodialysis patients with HCV
      infection: a multicentre, prospective study.
AB  - BACKGROUND: A prospective multicentre study was initiated in HCV-infected
      haemodialysis patients to assess the tolerance and efficacy of alpha-2b
      interferon. METHODS: We had planned to include 120 patients with HCV RNA
      detectable by polymerase chain reaction (PCR) (Amplicor Roche) and histologically
      documented chronic hepatitis. The dose of alpha-interferon was 3 million units
      (MU) three times weekly (TTW), to be reduced to 1.5 MU TTW in case of side
      effects. Tolerance was evaluated monthly; virological efficacy was evaluated by
      PCR. A liver biopsy was performed at month 18 (M18). RESULTS: (a) TOLERANCE:
      After 37 patients had been included, the study was discontinued by the promoting
      institution because of severe side-effects requiring that treatment be stopped in
      19 patients. The side-effects were: cardiac (4) neuropsychiatric (2), digestive
      (3), acute necrosis of the graft (1), severe asthenia (9), minor side-effects
      were observed in 22 patients. A complete 12-month course was completed in 12
      patients for the 3 MU TTW dose and in six patients for the 1.5 MU TTW reduced
      dose. Normal ALT level (OR, 0.16; CI 95%, 0.03-0.89) at inclusion was associated
      with interruption of treatment (univariate analysis). (b) EFFICACY: Sustained
      virological response was observed in only seven (18.9%), of the 18 patients who
      completed the treatment (38%). Increased ALT at inclusion (OR, 1.04; CI 95%, 1.01
      1.09) and cumulated doses of interferon (OR, 1.01; CI 95%, 1.004-1.026) were
      jointly associated with a sustained response, while positive PCR at M2 was
      strongly predictive of treatment failure. CONCLUSION: Tolerance of interferon is
      poor in haemodialysis patients. Sustained response is fairly high in patients who
      have 12 months of treatment and seems to be based on the immune status of the
      patients (ALT) and the cumulative doses of interferon.

PMID- 11328910
TI  - Peritoneal tuberculosis in patients receiving continuous ambulatory peritoneal
      dialysis.
AB  - BACKGROUND: Patients with chronic renal failure have an increased risk of
      tuberculosis (TB). This occurs with much higher frequency within the first 12
      months of initiating dialysis and is usually extrapulmonary in nature. Patients
      most at risk are those from susceptible ethnic groups, especially the Indian
      subcontinent. Peritoneal TB, otherwise relatively uncommon, has emerged as an
      important form of TB in patients undergoing continuous ambulatory peritoneal
      dialysis (CAPD). METHODS: All cases of peritoneal TB occurring at our institution
      in patients undergoing CAPD over a 13 year period were identified and analysed.
      RESULTS: Eight cases were identified, of which seven were non-Caucasian. These
      patients' characteristics and outcomes are presented. All were undergoing CAPD
      and most developed TB within 12 months of initiating dialysis. All presented with
      fever, but symptoms and signs were indistinguishable from bacterial peritonitis.
      Six were culture-positive, mainly from peritoneal dialysis fluid, but only two
      cases proved smear-positive. All were treated with standard anti-tuberculous
      chemotherapy. Three went on to permanent haemodialysis as a result of peritonitis
      and three have died, one of these as a result of TB. CONCLUSIONS: Peritoneal TB,
      whilst otherwise relatively uncommon, is an important manifestation of TB in CAPD
      patients and usually develops soon after commencing dialysis. The reasons for
      this are unknown and require further research.

PMID- 11328911
TI  - An economic and quality-of-life assessment of basiliximab vs antithymocyte
      globulin immunoprophylaxis in renal transplantation.
AB  - BACKGROUND: Immunosuppressive therapy with cyclosporin A has substantially
      improved clinical outcomes for renal transplantation. Whether basiliximab (a
      chimeric monoclonal antibody) demonstrates economic and quality-of-life
      advantages over other induction therapies has not yet been shown. METHODS: A
      multi-centre open-label clinical trial was conducted among renal transplant
      recipients in the US, in which patients were randomized into two induction
      therapy regimens: basiliximab and antithymocyte globulin (ATG) as part of a
      quadruple immunosuppressive regimen. Medical resources used and a EuroQol visual
      analogue scale (VAS) rating of quality of life were collected prospectively for
      the 135 dosed subjects for a period of 1 year post-treatment. We analysed the
      differences between treatment groups in 1-year costs and 1-year quality-adjusted
      survival. We also conducted a post hoc analysis of outcomes among the subgroup of
      patients identified as high risk. RESULTS: A significant difference was observed
      in first-year post-treatment costs (basiliximab, $45857; ATG, $54729; difference,
      $8872 (95% CI, $1169 to $16573). The savings from basiliximab can be attributed
      to the less expensive induction therapy (basiliximab, $2378; ATG, $8670;
      difference, $6292 (95% CI, $5165 to $7419)) and other savings during the initial
      hospitalization totalling $2609. One-year quality-adjusted survival was the same
      in both groups (basiliximab, 81.5; ATG, 81.1; difference, 0.45 (95% CI, -5.9 to
      6.8)). The results of the post hoc analysis of the 48 high-risk patients were
      comparable to the analysis of all patients. CONCLUSIONS: These results
      demonstrate lower first-year post-treatment costs in renal-transplant recipients
      receiving basiliximab compared to ATG with no differences in quality-adjusted
      survival. The results also suggest similar differences among high-risk subjects.

PMID- 11328912
TI  - The effect of ACE inhibitor and angiotensin II receptor antagonist therapy on
      serum uric acid levels and potassium homeostasis in hypertensive renal transplant
      recipients treated with CsA.
AB  - BACKGROUND: The angiotensin II (AT II) type I receptor antagonist losartan has
      been reported to increase urinary uric acid and potassium excretion. These
      effects might be beneficial in cyclosporin (CsA)-treated renal transplant
      recipients, who frequently suffer from hyperuricaemia and hyperkalaemia. METHODS:
      In this prospective, open, randomized, two-way cross-over study we included 13
      hypertensive CsA-treated patients after renal transplantation and administered
      either the angiotensin-converting enzyme (ACE) inhibitors enalapril or losartan.
      Laboratory parameters, 24-h urinary protein excretion, and mean 24-h arterial
      blood pressure (MAP) were checked after 3 weeks treatment with enalapril, after a
      wash-out period of 2 weeks, and before and after a 3-week treatment course with
      losartan. RESULTS: Both drugs slightly reduced MAP (losartan from 97+/-6 to 94+/
      9 and enalapril to 93+/-8 mmHg). Serum potassium levels significantly increased
      during enalapril therapy (from 4.3+/-0.5 to 4.8+/-0.4 mmol/l, P<0.05), as did,
      although not significantly, uric acid concentrations (from 7.8+/-1.9 to 8.2+/-1.8
      mg/dl, P=0.5). Losartan, on the contrary, only mildly affected serum potassium
      (4.3+/-0.5 vs 4.5+/-0.5 mmol/l, P=0.25) and serum uric acid decreased (from 7.8+/
      2.4 to 7.3+/-1.8 mg/dl, P=0.6). Serum aldosterone and urinary aldosterone
      excretion were significantly reduced only during ACE inhibitor treatment, which
      might explain the variable effects on potassium homeostasis. CONCLUSION: Losartan
      may be a useful agent to reduce blood pressure and serum uric acid levels in
      renal transplant recipients treated with CSA: Furthermore, in this high-risk
      population, the effects on serum potassium levels are less marked with losartan
      than with enalapril.

PMID- 11328913
TI  - Transperitoneal guide-wire or drainage catheter placement for guidance of
      laparoscopic marsupialization of lymphocoeles post renal transplantation.
AB  - BACKGROUND: Lymphocoeles post renal transplantation can be difficult to see
      laparoscopically. The objective of this study was to report a new technique of
      catheter or guide-wire placement for the guidance of laparoscopic
      marsupialization of symptomatic post renal transplant lymphocoeles, refractory to
      conservative therapy. METHODS: Conventional aseptic technique under local
      anaesthesia was used for guide-wire or catheter insertion, with the difference
      being the use of a transperitoneal approach. Computerized tomography (CT) or
      ultrasound (US) guidance was used. All lesions were confirmed to be sterile
      lymphocoeles beforehand by either needle aspiration or previous catheter
      drainage. RESULTS: Four catheters and one guide-wire were placed pre-operatively
      without complication. All cases underwent satisfactory laparoscopic
      marsupialization. No immediate complications were noted in any patient. The
      drainage catheters were inserted between 5 and 19 days before laparoscopic
      marsupialization, and guide-wire inserted immediately before. All patients
      proceeded to laparoscopic marsupialization. CONCLUSIONS: This technique offers
      precise guidance on laparoscopic surgery, is relatively simple to perform and no
      complications were experienced in this study. Its use is limited to sterile and
      benign lesions due to the risks of peritoneal seeding, making recurrent post
      operative lymphocoeles ideally suited for this application.

PMID- 11328914
TI  - Screening for renal disease using serum creatinine: who are we missing?
AB  - BACKGROUND: Appropriate management and timely referral of patients with early
      renal disease often depend on the identification of renal insufficiency by
      primary care physicians. Serum creatinine (SCr) levels are frequently used as a
      screening test for renal dysfunction; however, patients can have significantly
      decreased glomerular filtration rates (GFR) with normal range SCr values, making
      the recognition of renal dysfunction more difficult. This study was designed to
      estimate the prevalence of patients who have significantly reduced GFR as
      calculated by the Cockcroft-Gault (C-G) formula, but normal-range SCR: METHODS:
      The study included 2781 outpatients referred by community physicians to an urban
      laboratory network for SCr measurement. GFR was estimated using the C-G formula.
      Patients were grouped according to the concordance of SCr level abnormalities
      (abnormal >130 micromol/l) with significantly abnormal C-G values (abnormal </=50
      ml/min). The C-G value of < or =50 ml/min was chosen to reflect substantial renal
      impairment in all age groups. A further analysis of historical laboratory data
      was undertaken to determine if there were previously documented changes in renal
      function parameters in those patients who had overt renal dysfunction during the
      study period. RESULTS: Of the 2781 outpatients referred, 2543 (91.4%) had normal
      SCr levels. Of these patients, 387/2543 (15.2%) had C-G calculated GFR < or =50
      ml/min, representing substantially impaired renal function. Among patients with
      normal SCr, abnormal C-G values were identified in 47.3% > or =70 years old,
      12.6% 60-69 years old, and 1.2% 40-59 years old. Analysis of historical available
      laboratory data for patients with abnormal SCr and abnormal C-G values showed
      that 2 years prior to the study period, 72% of this group had abnormal SCr, while
      18% had normal SCr with abnormal C-G values, and 10% had normal SCr with normal C
      G values. CONCLUSIONS: This study documents the substantial prevalence of
      significantly abnormal renal function among patients identified by laboratories
      as having normal-range SCR: Including calculated estimates of GFR in routine
      laboratory reporting may help to facilitate the early identification of patients
      with renal impairment.

PMID- 11328915
TI  - Metabolic cardiovascular syndrome after renal transplantation.
AB  - BACKGROUND: Cardiovascular disease (CVD) is the major cause of death in renal
      transplant recipients. Traditional risk factors like hypertension, dyslipidaemia
      and diabetes mellitus are common, but cannot completely account for the high
      prevalence of CVD in this population. The aim of the present study was to assess
      whether post-transplant glucose intolerance, defined as post-transplant diabetes
      mellitus, impaired glucose tolerance, or impaired fasting glucose, is associated
      with metabolic disturbances known to increase risk of cardiovascular disease,
      similar to what has been observed in the general population. METHODS: One hundred
      and seventy-three consecutive patients were prospectively examined 10 weeks after
      transplantation. An oral glucose tolerance test was completed in 167 patients.
      Questionnaires, medical records, and the results of various blood tests were used
      to evaluate a number of known cardiovascular risk factors in all patients.
      RESULTS: Glucose intolerance was present in about one-half the recipients and was
      associated with age, a positive family history of ischaemic heart disease, acute
      rejection, higher levels of serum triglycerides, apolipoprotein B and 2-h
      insulin, and lower levels of serum HDL cholesterol. After adjustment for age and
      sex, lower HDL cholesterol (P=0.005), higher serum triglycerides (P<0.001),
      apolipoprotein B (P=0.039) and 2-h insulin (P<0.001) were still associated with
      post-transplant glucose intolerance. CONCLUSIONS: Ten weeks after renal
      transplantation glucose intolerance is associated with a clustering of
      cardiovascular risk factors and metabolic abnormalities, consistent with a post
      transplant metabolic cardiovascular syndrome.

PMID- 11328916
TI  - Accuracy and safety of online clearance monitoring based on conductivity
      variation.
AB  - BACKGROUND: Haemodialysis dose has been shown to have a distinct impact upon the
      morbidity and mortality rate in patients on regular dialysis therapy.
      Accordingly, the adequacy of dialysis treatment should be guaranteed. METHODS: In
      200 dialysis sessions two or three +/-10% dialysate conductivity variations were
      applied to test patient compliance and the accuracy of an electrolyte based
      online clearance measurement (OCM) reflecting the total clearance of urea.
      RESULTS: Using a step profile the electrolytic clearance showed highly
      significant correlation with the reference data in the blood side (n=118,
      r=0.867, P<0.001) and dialysate side (n=118, r=0.820, P<0.001) if only reference
      values were taken into account for which the error in mass balance did not exceed
      5%. Kt/V according to the single pool model (n=35, r=0.940, P<0.001), the
      equilibrated single pool variable volume kinetic model (n=36, r=0.982, P<0.001),
      Daugirdas formula (n=34, r=0.951, P<0.001) and direct quantification of
      dialysance via spent dialysate (n=26, r=0.900, P<0.001) showed outstanding
      correlations with electrolyte-based Kt/V at mass balance error below 5%. No
      adverse clinical effect of OCM was reported. Serum sodium, body weight, heart
      rate and breathing rate at rest, arterial pO(2) and pCO(2) and blood pressure
      before haemodialysis remained unaffected in OCM measurements in comparison with
      baseline parameters. A small influx of sodium (1.53+/-7.62 mmol) into the patient
      was seen following the impulse, but no signs associated with fluid overload were
      observed during the study period of 10 consecutive dialysis sessions.
      CONCLUSIONS: The OCM option of the haemodialysis machine provides a safe and
      accurate tool for continuous online monitoring of total urea clearance.

PMID- 11328917
TI  - Renal failure in a patient with leukaemic infiltration of the kidney and
      polyomavirus infection.

PMID- 11328918
TI  - Unusual bacterial infections of the urinary tract in diabetic patients--rare but
      frequently lethal.

PMID- 11328919
TI  - The tell-tale urinary chloride.

PMID- 11328920
TI  - Nasty shock after an anti-emetic.

PMID- 11328921
TI  - Nephrocalcinosis induced by furosemide in an adult patient with incomplete renal
      tubular acidosis.

PMID- 11328922
TI  - CaCO(3) dose and risk of arterial calcification.

PMID- 11328923
TI  - Anaemia correction--does the mode of dialysis matter?

PMID- 11328924
TI  - Intravenous administration of iron in epoetin-treated haemodialysis patients.

PMID- 11328925
TI  - The impact of dialyzers on the anaemia of haemodialysis patients.

PMID- 11328926
TI  - Severe haemorrhage and retroperitoneal haematoma secondary to renal biopsy.

PMID- 11328927
TI  - A case of nondissecting abdominal aortic aneurysm associated with systemic lupus
      erythematosus.

PMID- 11328928
TI  - Henoch-Schonlein nephritis and non-Hodgkin's lymphoma.

PMID- 11328929
TI  - Henoch-Schonlein nephritis and salmonella typhi septicaemia.

PMID- 11328930
TI  - Radiation nephropathy after radiotherapy in metastatic medullary thyroid
      carcinoma.

PMID- 11328931
TI  - Waldenstrom's macroglobulinaemia and acute renal failure: isoosmolal non-ionic
      contrast medium is not an absolute contraindication.

PMID- 11328932
TI  - Hypertensive rebound after angiotensin converting enzyme inhibitor withdrawal in
      diabetic patients with chronic renal failure.

PMID- 11328933
TI  - Haemoglobin, not haematocrit, should be the preferred parameter for the
      evaluation of anaemia in renal patients.

PMID- 11328934
TI  - The (dP/dt)max derived from arterial pulse waveforms: prospective applications in
      the haemodialysis setting.

PMID- 11328935
TI  - Severe methotrexate intoxication in a haemodialysis patient treated for
      rheumatoid arthritis.

PMID- 11328936
TI  - Haemoperfusion combined with haemodialysis in ifosfamide intoxication.

PMID- 11328937
TI  - Inability to monitor polyurethane haemodialysis vascular access graft by Doppler
      ultrasound.

PMID- 11328938
TI  - Serum potassium levels and atrial fibrillation in haemodialysis patients.

PMID- 11328941
TI  - Intestinal motility disorders and development of the enteric nervous system.

PMID- 11328942
TI  - Hypoxia-inducible factor 1: control of oxygen homeostasis in health and disease.
AB  - Hypoxia-inducible factor 1 (HIF-1) is a transcriptional activator that mediates
      changes in gene expression in response to changes in cellular oxygen
      concentrations. HIF-1 is a heterodimer consisting of an oxygen-regulated HIF-1
      alpha subunit and a constitutively expressed HIF-1 beta subunit. In mice,
      complete HIF-1 alpha deficiency results in embryonic lethality at midgestation
      because of cardiac and vascular malformations. Analyses of animal and cell
      culture models as well as human tissue have provided evidence that HIF-1 plays
      important roles in the pathophysiology of preeclampsia, intrauterine growth
      retardation, hypoxia-mediated pulmonary hypertension, and cancer. HIF-1 promotes
      neovascularization in response to myocardial or retinal ischemia by activating
      transcription of the gene encoding vascular endothelial growth factor. HIF-1 may
      also mediate the protective response to cerebral ischemia known as late-phase
      preconditioning.

PMID- 11328943
TI  - Epidermolysis bullosa with congenital pyloric atresia: novel mutations in the
      beta 4 integrin gene (ITGB4) and genotype/phenotype correlations.
AB  - Epidermolysis bullosa with pyloric atresia (EB-PA: OMIM 226730), also known as
      Carmi syndrome, is a rare autosomal recessive genodermatosis that manifests with
      neonatal mucocutaneous fragility associated with congenital pyloric atresia. The
      disease is frequently lethal within the first year, but nonlethal cases have been
      reported. Mutations in the genes encoding subunit polypeptides of the alpha 6
      beta 4 integrin (ITGA6 and ITGB4) have been demonstrated in EB-PA patients. To
      extend the repertoire of mutations and to identify genotype-phenotype
      correlations, we examined seven new EB-PA families, four with lethal and three
      with nonlethal disease variants. DNA from patients was screened for mutations
      using heteroduplex analysis followed by nucleotide sequencing of PCR products
      spanning all beta 4 integrin-coding sequences. Mutation analysis disclosed 12
      distinct mutations, 11 of them novel. Four mutations predicted a premature
      termination codon as a result of nonsense mutations or small out-of-frame
      insertions or deletions, whereas seven were missense mutations. This brings the
      total number of distinct ITGB4 mutations to 33. The mutation database indicates
      that premature termination codons are associated predominantly with the lethal EB
      PA variants, whereas missense mutations are more prevalent in nonlethal forms.
      However, the consequences of the missense mutations are position dependent, and
      substitutions of highly conserved amino acids may have lethal consequences. In
      general, indirect immunofluorescence studies of affected skin revealed negative
      staining for beta 4 integrin in lethal cases and positive, but attenuated,
      staining in nonlethal cases and correlated with clinical phenotype. The data on
      specific mutations in EB-PA patients allows prenatal testing and preimplantation
      genetic diagnosis in families at risk.

PMID- 11328944
TI  - Whole-body L-leucine oxidation in patients with variant form of maple syrup urine
      disease.
AB  - Whole-body L-leucine oxidation was assessed in patients with maple syrup urine
      disease of different severity using oral L-[1-(13)C]leucine bolus tests (38
      micromol/kg body weight). Residual whole-body L-leucine oxidation was estimated
      on the basis of the 3-h kinetics of (13)CO(2) exhalation and (13)C-isotopic
      enrichment in plasma 4-methyl-2-oxopentanoate using a noncompartmental
      mathematical approach. In four patients with classical maple syrup urine disease
      (two females and two males; mean age, 13 +/- 5 y; range, 7--17 y), L-leucine
      oxidation was too low to be measurable. In two females (aged 11 and 15 y) with a
      severe variant form of the disease, whole-body L-leucine oxidation was reduced to
      about 4% of control. In six milder variants (two females and four males; mean age
      +/- SD, 15 +/- 10 y; range, 6--34 y), the estimates for residual whole-body L
      leucine oxidation ranged from 19 to 86% (59 +/- 24%) of control and were
      substantially higher than the residual branched-chain 2-oxo acid dehydrogenase
      complex activities in the patients' fibroblasts (10--25% of control). Possible
      mechanisms are considered that might contribute to a comparatively high residual
      in vivo L-leucine oxidation in (mild) variant maple syrup urine disease.

PMID- 11328945
TI  - Congenital heart disease in maternal phenylketonuria: report from the Maternal
      PKU Collaborative Study.
AB  - The frequency and types of congenital heart disease in offspring from pregnancies
      in women with hyperphenylalaninemia were examined in the international
      prospective Maternal Phenylketonuria Collaborative Study. Relationships of
      congenital heart disease in offspring to the basal blood phenylalanine level in
      the mother, metabolic control through diet during pregnancy, and phenylalanine
      hydroxylase mutations in mother and offspring were determined. The 416 offspring
      from 412 maternal phenylketonuria pregnancies that produced live births and 100
      offspring from the 99 control pregnancies were included in this examination.
      Thirty-four of the 235 offspring (14%; 95% CI, 10.2 to 19.6%) from pregnancies in
      phenylketonuric women with a basal phenylalanine level > or = 900 microM (15
      mg/dL) [normal blood phenylalanine < 120 microM (2 mg/dL)] and not in metabolic
      control [phenylalanine level < or = 600 microM (10 mg/dL)] by the eighth
      gestational week had congenital heart disease compared with one control offspring
      (1%) with congenital heart disease. One offspring among the 50 (2%) from mothers
      with non-phenylketonuria mild hyperphenylalaninemia also had congenital heart
      disease. Coarctation of the aorta and hypoplastic left heart syndrome were
      overrepresented compared with expected percentages among those with congenital
      heart disease in the general population. A basal maternal phenylalanine level >
      1800 microM (30 mg/dL) significantly increased the risk for bearing a child with
      congenital heart disease (p = 0.003). Phenylalanine hydroxylase mutations in the
      mothers and offspring did not have an independent relationship to congenital
      heart disease but were related through the basal maternal phenylalanine levels.
      The data in this study indicate that a basal maternal phenylalanine level of 900
      microM may be a threshold for congenital heart disease, that women with the most
      severe degree of phenylketonuria are at highest risk for bearing such a child,
      and that prevention of the congenital heart disease requires initiation of the
      low phenylalanine diet before conception or early in pregnancy with metabolic
      control no later than the eighth gestational week.

PMID- 11328946
TI  - Increased risk of intraventricular hemorrhage in preterm infants with
      thrombophilia.
AB  - The multifactorial etiology of cerebral intraventricular hemorrhage (IVH) may
      involve coagulation disturbances and venous infarction. We tested whether
      coagulation abnormalities associated with adult venous thrombosis would
      constitute a risk factor for IVH in newborn infants. In 22 infants (gestational
      age 24.3--39.9 wk, median 28.0 wk) with neonatal IVH grade II to IV, the
      frequencies of congenital resistance to activated protein C due to a point
      mutation in the factor V gene (Gln506-FV) and a polymorphism in the prothrombin
      gene (G20210A-FII) were assessed and compared with those observed in 29 premature
      newborn infants without IVH and in 302 (Gln506-FV) or 526 (G20210A-FII) healthy
      adults. In infants with IVH, four (18%) heterozygous carriers of Gln506-FV and
      one (5%) heterozygous carrier of G20210A-FII were found. One infant without IVH
      was heterozygous for Gln506-FV (3%). When compared with the frequency of Gln506
      FV in the general population, the odds ratio for being a carrier of Gln506-FV for
      patients with IVH was 5.9 (95% confidence interval 1.7--20.3, p = 0.013) and for
      patients without IVH 0.9 (95% confidence interval 0.1--7.6, p > 0.99). The
      absolute risk of IVH in a newborn infant with heterozygous Gln506-FV and born
      before 30 wk of gestation was estimated at 80%, whereas the corresponding risk
      for all infants born before 30 wk was 14%. Gln506-FV was more common in newborn
      infants with IVH than in the general population, whereas there was no difference
      in the frequencies of Gln506-FV in infants without IVH and in the general
      population. Thus, Gln506-FV may be a risk factor of IVH. The risk of IVH in a
      premature infant with Gln506-FV or other established thrombophilic coagulation
      abnormality may be considerable.

PMID- 11328947
TI  - Effect of polyunsaturated fatty acid (PUFA) supplementation on intestinal
      inflammation and necrotizing enterocolitis (NEC) in a neonatal rat model.
AB  - Inasmuch as long-chain polyunsaturated fatty acids (PUFA, metabolites of the
      essential n-3 and n-6 fatty acids) are known to modulate inflammation, we
      hypothesized that supplementation of formula with these compounds would prevent
      necrotizing enterocolitis (NEC) and intestinal inflammation in our neonatal rat
      model. Newborn rats were stressed with asphyxia and formula feeding, and randomly
      assigned to control formula, control with PUFA supplementation, and PUFA with
      nucleotides. Animals were followed for 72--96 h and assessed for death, gross and
      histologic NEC, intestinal apoptosis, endotoxemia, and intestinal mRNA synthesis
      of phospholipase A(2)-II (rate-limiting enzyme for platelet activating factor
      production), platelet activating factor receptor, and inducible nitric oxide
      synthase. We found that PUFA reduced the incidence of death and NEC compared with
      the other groups (NEC 8 of 24 versus 17 of 24 control and 13 of 23 PUFA +
      nucleotides, p < 0.05). Furthermore, PUFA reduced plasma endotoxemia at 48 h (25
      +/- 4 EU/mL versus 276 +/- 39 EU/mL in control and 170 +/- 28 EU/mL in PUFA +
      nucleotide), intestinal phospholipase A(2)-II expression at 24 h, and platelet
      activating factor receptor expression at 48 h. Formula supplementation had no
      effect on apoptosis of intestinal epithelium or intestinal inducible nitric oxide
      synthase expression. Addition of nucleotides with PUFA abrogated the beneficial
      effects of PUFA on intestinal inflammation. We conclude that PUFA reduces the
      incidence of NEC and intestinal inflammation in a neonatal rat model.

PMID- 11328949
TI  - Overexpression of human insulin-like growth factor binding protein-1 in the mouse
      leads to nephron deficit.
AB  - IGFs and their binding proteins are important regulators of fetal development. We
      have previously reported that overexpression of the human IGF binding protein-1
      in mice is associated with glomerulosclerosis. The aim of this study was to
      investigate whether, in that model, decreased bioavailability of IGFs also
      affected nephrogenesis. When the mothers expressed human IGF binding protein-1,
      pups were growth retarded and had a reduced number of nephrons. Even
      nontransgenic pups born to heterozygous mothers had a nephron reduction,
      indicating that renal hypoplasia was secondary to fetal growth retardation. When
      the transgene was expressed only in the fetus, pups had a normal birth weight and
      the kidney was normal at birth, as indicated by histologic studies. However, a
      significant reduction in the nephron number was observed at 3 mo of age. Because
      nephrogenesis continues for a few days after birth in the mouse, this indicated
      that human IGF binding protein-1 overexpression altered postnatal nephrogenesis.
      In addition, exogenously added IGF-II, but not IGF-I, was effective in
      stimulating in vitro nephrogenesis. Together these elements suggest that reduced
      amounts of circulating IGFs, presumably IGF-II, impair kidney development.

PMID- 11328948
TI  - von Willebrand factor and von Willebrand factor-cleaving metalloprotease activity
      in Escherichia coli O157:H7-associated hemolytic uremic syndrome.
AB  - Hemolytic uremic syndrome (HUS) usually occurs after infection with Shiga toxin
      producing bacteria. Thrombotic thrombocytopenic purpura, a disorder with similar
      clinical manifestations, is associated with deficient activity of a circulating
      metalloprotease that cleaves von Willebrand factor at the Tyr842-Met843 peptide
      bond in a shear stress-dependent manner. We analyzed von Willebrand factor
      cleaving metalloprotease activity and the status of von Willebrand factor in 16
      children who developed HUS after Escherichia coli O157:H7 infection and in 29
      infected children who did not develop this complication. Von Willebrand factor
      cleaving metalloprotease activity was normal in all subjects, but von Willebrand
      factor size was decreased in the plasma of each of 16 patients with HUS. The
      decrease in circulating von Willebrand factor size correlated with the severity
      of thrombocytopenia and was proportional to an increase in von Willebrand factor
      proteolytic fragments in plasma. Immunohistochemical studies of the kidneys in
      four additional patients who died of HUS demonstrated glomerular thrombi in three
      patients, and arterial and arteriolar thrombi in one patient. The glomerular
      thrombi contained fibrin but little or no von Willebrand factor. A decrease in
      large von Willebrand factor multimers, presumably caused by enhanced proteolysis
      from abnormal shear stress in the microcirculation, is common in HUS.

PMID- 11328950
TI  - Fetal leptin influences birth weight in twins with discordant growth.
AB  - The objective of this study was to determine the plasma leptin concentrations in
      twin pregnancies in relation to chorionicity and discordant fetal growth. We
      studied 53 twin pregnancies of which 26 had growth discordance of > or =20% and
      27 were concordant for growth (discordance of < or =10%). Paired maternal and
      fetal blood samples were obtained at birth. Plasma leptin concentrations were
      measured by RIA. In discordant monochorionic pregnancies, fetal plasma leptin
      concentrations in the intrauterine growth-restricted twins were lower than the co
      twins with normal growth (mean difference, 3 ng/mL; 95% CI, 2.2 to 3.3 ng/mL; p <
      0.001), whereas no such differences were present between concordant monochorionic
      twin pairs (mean difference, 0.1 ng/mL; 95% CI, -0.2 to 0.5 ng/mL; NS).
      Similarly, fetal plasma leptin concentrations in appropriate-for-gestational-age
      twins were higher than in the intrauterine growth-restricted twins of the
      discordant dichorionic pregnancies (mean difference, 2.4 ng/mL; 95% CI, 1.8 to
      3.1 ng/mL; p < 0.001). No such differences were present between the concordant
      dichorionic twin pairs (mean difference, 0.2 ng/mL; 95% CI, -0.1 to 0.5 ng/mL;
      NS). Maternal plasma leptin concentrations were comparable among all four groups
      and were higher than the fetal levels. Fetal plasma leptin concentrations of the
      intrauterine growth-restricted twins of discordant monochorionic and dichorionic
      pregnancies were comparable. There was a positive association between cord plasma
      leptin concentrations and the birth weight of twin pairs (y = 0.002x - 0.32; r =
      0.63; p < 0.001; n = 106). A significant positive association was also found
      between percent differences in birth weight and fetal delta plasma leptin
      concentrations of the discordant monochorionic and dichorionic twin pairs (y =
      0.057x + 0.93; r = 0.60; p < 0.001, n = 26). In conclusion, irrespective of
      chorionicity, plasma leptin concentrations in intrauterine growth-restricted
      twins were 2-fold lower than their co-twins with normal growth. These differences
      may be attributed to placental factors.

PMID- 11328951
TI  - Growth, neurobehavioral and circadian rhythm development in newborn baboons.
AB  - We measured body temperature continuously using telemetry to determine the
      development of circadian rhythmicity in neonatal baboons after birth. Twelve
      fetal baboons (nine males and three females) of known gestational age ranging
      from 167 to 193 d were studied. We eliminated the influence of maternal factors
      by hand rearing these infants from the moment of birth until 45 d of life. All
      infants showed steady growth in body weight, head circumference, and crown-rump
      length. Neurobehavioral responses including visual and auditory orientation,
      motor maturity, irritability, and consolability increased as a function of age.
      Circadian rhythms of body temperature were present in the second week of life,
      and the amplitude of this rhythm increased throughout the developmental period
      studied. The increase in the amplitude of circadian body temperature rhythm
      independent of environmental time cues may indicate the maturation of the brain.
      These neonatal nonhuman primates offer an excellent model for studying
      neurobehavioral development and maturation of circadian rhythms while controlling
      external factors in a manner that is not possible with human neonates.

PMID- 11328952
TI  - Plasma osmolality dipsogenic thresholds and c-fos expression in the near-term
      ovine fetus.
AB  - In ovine and human pregnancy, fetal swallowing contributes importantly to
      amniotic fluid homeostasis. Fetal dipsogenic responsiveness to short-term plasma
      hyperosmolality develops in late gestation, although fetal swallowing is not
      stimulated in response to long-term plasma osmolality increases (2 to 3%), which
      typically stimulate adult drinking behavior. To explore the near-term fetal
      plasma osmolality threshold for swallowing stimulation, we examined the effects
      of i.v. hypertonic saline-induced subacute increases in plasma hypertonicity on
      fetal swallowing behavior. Central sites of activation were examined by c-fos
      expression in putative dipsogenic nuclei. The results demonstrate that subacute 2
      to 3% plasma osmolality increases do not stimulate near-term ovine fetal
      swallowing. However, fetal swallowing activity significantly increased (3 times)
      after plasma osmolality increased >6% above basal values. Consistent with a
      specific dipsogenic response, i.v. hypertonic saline induced c-fos expression in
      the anterior third ventricle region, a putative dipsogenic center, as well as in
      the fetal hindbrain. The stimulation of fetal swallowing under conditions of
      higher osmotic stimulation and the correlation with forebrain c-fos expression
      indicates that near-term fetal osmoregulation mechanisms are functional, although
      not completely mature. Reduced fetal dipsogenic responsiveness may result from
      altered osmoreceptor sensitivity, downstream neuronal or synaptic immaturity, or
      potentially inhibitory actions of stimulated hindbrain nuclei.

PMID- 11328954
TI  - Different cytokine expression in cord blood mononuclear cells after stimulation
      with neonatal sepsis or colonizing strains of Streptococcus agalactiae.
AB  - Streptococcus agalactiae (group B streptococcus, GBS) is the major pathogen of
      neonatal sepsis. In some newborns, GBS sepsis may have a severe course, including
      septic shock with a high mortality rate, whereas other newborns are colonized
      with GBS on their surfaces without any clinical signs of bacterial infection. The
      reason for this discrepancy is far from clear. We sought, in this study, to
      compare cytokine expression in cord blood mononuclear cells after stimulation
      with GBS strains isolated from newborns with sepsis, and strains isolated from
      newborns without any symptoms of invasive infection. Cord blood mononuclear cells
      were incubated with either heat-killed bacteria of different strains or
      lipopolysaccharide, respectively. After 6 and 24 h, cells were harvested and
      cytokine mRNA-expression was analyzed by reverse-transcriptase PCR. Likewise,
      supernatants were tested for IL-6 and tumor necrosis factor-alpha concentrations
      by enzyme immunoassay. When comparing IL-6 and tumor necrosis factor-alpha
      secretion, there were significantly higher IL-6 levels after stimulation with
      sepsis than with colonizing isolates. Likewise, mRNA expression of IL-6, IL-1
      beta, and IL-12p40 was significantly higher after stimulation with sepsis
      isolates. This was also true when normalizing to cytokine expression after
      stimulation with lipopolysaccharide. These findings indicate that the different
      clinical pictures in response to GBS, either septic infection or colonization,
      might reflect strain-specific properties. If the respective characteristics can
      be defined, it might become possible to distinguish by molecular methods
      potentially "dangerous" from "harmless" strains. Moreover, our findings underline
      the essential role of these cytokines in the pathogenesis of neonatal GBS sepsis.

PMID- 11328953
TI  - Increased frequency of alleles associated with elevated tumor necrosis factor
      alpha levels in children with Kawasaki disease.
AB  - Genetic polymorphisms influence the magnitude of the cytokine response after an
      inflammatory stimulus. To determine whether such polymorphisms might play a role
      in Kawasaki disease (KD), we analyzed white and Japanese children with KD and
      control populations for two polymorphic loci in which the A allele is associated
      with high tumor necrosis factor-alpha secretion. The lymphotoxin-alpha+250 A/A
      genotype was overrepresented among white children with KD compared with controls
      (0.59 versus 0.36; p = 0.013). The tumor necrosis factor-alpha-308 A/G genotype
      was overrepresented among whites with KD who had coronary artery abnormalities
      compared with those with normal echocardiograms (0.36 versus 0.09; p = 0.044). No
      significant difference was seen at either locus between Japanese children with KD
      and Japanese controls. The increased frequency of the high secretor alleles in
      white children with KD suggests that these loci may be related to susceptibility
      to KD and to outcome after disease.

PMID- 11328955
TI  - Hypoxia in fetal lambs: a study with (1)H-MNR spectroscopy of cerebrospinal
      fluid.
AB  - In fetal lambs, severe hypoxia (SH) will lead to brain damage. Mild hypoxia (MH)
      is thought to be relatively safe for the fetal brain because compensating
      mechanisms are activated. We questioned whether MH, leading to mild acidosis,
      induces changes in cerebral metabolism. Metabolites in cerebrospinal fluid (CSF)
      samples, as analyzed by proton magnetic resonance spectroscopy, were studied in
      two groups of seven anesthetized near-term fetal lambs. In group I, SH leading to
      acidosis with an arterial pH <7.1 was achieved. In group II, MH with an intended
      pH of 7.23--7.27 was reached [start of MH (SMH)], and maintained during 2 h [end
      of MH (EMH)]. During SH, choline levels in CSF, a possible indicator of cell
      membrane damage, were increased. Both during SH and at EMH, CSF levels of lactic
      acid, alanine, phenylalanine, tyrosine, lysine, branched chain amino acids, and
      hypoxanthine were increased compared with control values and with SMH,
      respectively. At EMH, the hypoxanthine CSF-to-blood ratio was increased as
      compared with SMH. These results indicate that prolonged MH leads to energy
      degradation in the fetal lamb brain and may not be as safe as assumed.

PMID- 11328956
TI  - Impaired ventilatory responses to hypoxia in mice deficient in endothelin
      converting-enzyme-1.
AB  - Endothelin-converting-enzyme (ECE-1) catalyzes the proteolytic activation of big
      endothelin-1 to mature endothelin-1. Most homozygous ECE-1-/- embryos die in
      utero and show severe craniofacial, enteric, and cardiac malformations precluding
      ventilatory function assessment. In contrast, heterozygous ECE-1+/- embryos
      develop normally. Their respiratory function at birth has not been studied.
      Taking into account previous respiratory investigations in mice with endothelin-1
      gene disruption, we hypothesized that ECE-1-deficient mice may have impaired
      ventilatory control. We analyzed ventilatory responses to hypercapnia (8% CO(2))
      and hypoxia (10% O(2)) in newborn and adult mice heterozygous for ECE-1
      deficiency (ECE-1+/-) and in their wild-type littermates (ECE-1+/+). Ventilation,
      breath duration, and tidal volume were measured using whole-body plethysmography.
      Ventilatory responses to hypoxia were significantly weaker in ECE-1+/- than in
      ECE-1+/+ newborn mice (percentage ventilation increase: 1 +/- 25% versus 33 +/-
      29%, p = 0.010). Baseline breathing variables and ventilatory responses to
      hypercapnia were normal in the ECE-1+/- newborn mice. No differences were
      observed between adult ECE-1+/- and ECE-1+/+ mice. We conclude that ECE-1 is
      required for normal ventilatory response to hypoxia at birth.

PMID- 11328957
TI  - Bone quality assessment by quantitative ultrasound of proximal phalanxes of the
      hand in healthy subjects aged 3--21 years.
AB  - Bone quality by quantitative ultrasound was assessed in 1083 (587 males) healthy
      white subjects aged 3--21 y. Amplitude-dependent speed of sound (AD-SoS) through
      the distal end of the first phalanx diaphysis of the last four fingers of the
      hand was measured by an ultrasound device (DBM Sonic 1200, IGEA, Carpi, Italy).
      Mean AD-SoS values increased progressively from 3 to 21 y (males, 1845.9--2119.1
      m/s, p < 0.0001; females, 1842.3--2098.8 m/s, p < 0.0001). They did not differ (p
      = NS) between sexes up to age 11, but females showed higher (p < 0.05 - p <
      0.0001) AD-SoS values than males in age groups 12, 13, and 14 y. There was no
      difference (p = NS) of AD-SoS values between sexes in pubertal stages 1, 2, and
      5, but females had higher mean AD-SoS values than males in stages 3 (p < 0.01)
      and 4 (p < 0.001). Independent predictors of AD-SoS were weight, body mass index,
      pubertal stage, and mean width of fingers in males, and age, pubertal stage, and
      mean width of fingers in females (p < 0.01 - p < 0.0001). However, 7.8% in males
      and 3.6% in females of the increment of AD-SoS values can be related to the
      finger anatomy alone. AD-SoS values probably reflect the architectural
      organization of growing bone or changes in bone elasticity. Increased bone
      density and size may be additional factors influencing AD-SOS: Measurement of AD
      SoS at the hand phalanxes may be a simple, noninvasive, and radiation-free
      technique to assess bone quality in children.

PMID- 11328958
TI  - Feeding preterm infants after hospital discharge: growth and development at 18
      months of age.
AB  - We have shown that preterm infants fed a preterm formula grow better than those
      fed a standard term infant formula after hospital discharge. The purpose of this
      follow-up study was to determine whether improved early growth was associated
      with later growth and development. Preterm infants (< or =1750 g birth weight, <
      or =34 wk gestation) were randomized to be fed either a preterm infant formula
      (discharge to 6 mo corrected age), or a term formula (discharge to 6 mo), or the
      preterm (discharge to term) and the term formula (term to 6 mo). Anthropometry
      was performed at 12 wk and 6, 12, and 18 mo. Mental and psychomotor development
      were assessed using the Bayley Scales of Infant Development II at 18 mo.
      Differences in growth observed at 12 wk were maintained at 18 mo. At 18 mo, boys
      fed the preterm formula were 1.0 kg heavier, 2 cm longer, and had a 1.0 cm
      greater occipitofrontal circumference than boys fed the term formula. Boys fed
      the preterm formula were also 600 g heavier and 2 cm longer than girls fed the
      preterm formula. However, no differences were noted in MDI or PDI between boys
      fed the preterm formula and boys fed the term formula or between the boys fed
      preterm formula and girls fed the preterm formula. Overall, boys had
      significantly lower MDI than girls (mean difference, 6.0; p < 0.01), primarily
      reflecting lower scores in boys fed the term formula. Thus, early diet has long
      term effects on growth but not development at 18 mo of age. Sex remains an
      important confounding variable when assessing growth and developmental outcome in
      these high-risk infants.

PMID- 11328959
TI  - American Pediatric Society John Howland Award 2000: presentation.

PMID- 11328960
TI  - American Pediatric Society John Howland Award 2000: acceptance. A mentor's joys
      and responsibilities.

PMID- 11328961
TI  - Monitoring expression of genes involved in drug metabolism and toxicology using
      DNA microarrays.
AB  - Oligonucleotide DNA microarrays were investigated for utility in measuring global
      expression profiles of drug metabolism genes. This study was performed to
      investigate the feasibility of using microarray technology to minimize the long,
      expensive process of testing drug candidates for safety in animals. In an
      evaluation of hybridization specificity, microarray technology from Affymetrix
      distinguished genes up to a threshold of approximately 90% DNA identity.
      Oligonucleotides representing human cytochrome P-450 gene CYP3A5 showed
      heterologous hybridization to CYP3A4 and CYP3A7 RNAs. These genes could be
      clearly distinguished by selecting a subset of oligonucleotides that hybridized
      selectively to CYP3A5. Further validation of the technology was performed by
      measuring gene expression profiles in livers of rats treated with vehicle, 3
      methylcholanthrene (3MC), phenobarbital, dexamethasone, or clofibrate and by
      confirming data for six genes using quantitative RT-PCR. Responses of drug
      metabolism genes, including CYPs, epoxide hydrolases (EHs), UDP-glucuronosyl
      transferases (UGTs), glutathione sulfotransferases (GSTs), sulfotransferases
      (STs), drug transporter genes, and peroxisomal genes, to these well-studied
      compounds agreed well with, and extended, published observations. Additional gene
      regulatory responses were noted that characterize metabolic effects or stress
      responses to these compounds. Thus microarray technology can provide a facile
      overview of gene expression responses relevant to drug metabolism and toxicology.

PMID- 11328962
TI  - Cardiac remodeling and contractile function in acid alpha-glucosidase knockout
      mice.
AB  - Pompe's disease is an autosomal recessive and often fatal condition, caused by
      mutations in the acid alpha-glucosidase gene, leading to lysosomal glycogen
      storage in heart and skeletal muscle. We investigated the cardiac phenotype of an
      acid alpha-glucosidase knockout (KO) mouse model. Left ventricular weight-to-body
      weight ratios were increased 6.3 +/- 0.8 mg/g in seven KO compared with 3.2 +/-
      0.2 mg/g in eight wild-type (WT) mice (P < 0.05). Echocardiography under ketamine
      xylazine anesthesia revealed an increased left ventricular (LV) wall thickness
      (2.17 +/- 0.16 in KO vs. 1.18 +/- 0.10 mm in WT mice, P < 0.05) and a decreased
      LV lumen diameter (2.50 +/- 0.32 in KO vs. 3.21 +/- 0.14 mm in WT mice, P <
      0.05), but LV diameter shortening was not different between KO and WT mice. The
      maximum rate of rise of left ventricular pressure (LV dP/dt(max)) was lower in KO
      than in WT mice under basal conditions (2,720 +/- 580 vs. 4,440 +/- 440 mmHg/s)
      and during dobutamine infusion (6,220 +/- 800 vs. 8,730 +/- 790 mmHg/s, both P <
      0.05). Similarly, during isoflurane anesthesia LV dP/dt(max) was lower in KO than
      in WT mice under basal conditions (5,400 +/- 670 vs. 8,250 +/- 710 mmHg/s) and
      during norepinephrine infusion (10,010 +/- 1,320 vs. 14,710 +/- 220 mmHg/s, both
      P < 0.05). In conclusion, the markedly increased LV weight and wall thickness,
      the encroachment of the LV lumen, and LV dysfunction reflect cardiac
      abnormalities, although not as overt as in humans, of human infantile Pompe's
      disease and make these mice a suitable model for further investigation of
      pathophysiology and of novel therapies of Pompe's disease.

PMID- 11328963
TI  - Soa genotype selectively affects mouse gustatory neural responses to sucrose
      octaacetate.
AB  - In mice, behavioral acceptance of the bitter compound sucrose octaacetate (SOA)
      depends on allelic variation of a single gene, Soa. The SW.B6-Soa(b)congenic
      mouse strain has the genetic background of an "SOA taster" SWR/J strain and an
      Soa-containing donor chromosome fragment from an "SOA nontaster" C57BL/6J strain.
      Using microsatellite markers polymorphic between the two parental strains, we
      determined that the donor fragment spans 5-10 cM of distal chromosome 6. The
      SWR/J mice avoided SOA in two-bottle tests with water and had strong responses to
      SOA in two gustatory nerves, the chorda tympani (CT) and glossopharyngeal (GL).
      In contrast, the SW.B6-Soa(b) mice were indifferent to SOA in two-bottle tests
      and had very weak responses to SOA in both of these nerves. The SWR/J and SW.B6
      Soa(b) mice did not differ in responses of either nerve to sucrose, NaCl, HCl, or
      the bitter-tasting stimuli quinine, denatonium, strychnine, 6-n-propylthiouracil,
      phenylthiocarbamide, and MgSO(4). Thus the effect of the Soa genotype on SOA
      avoidance is mediated by peripheral taste responsiveness to SOA, involving taste
      receptor cells innervated by both the CT and GL nerves.

PMID- 11328964
TI  - Microarray analysis of nicotine-induced changes in gene expression in endothelial
      cells.
AB  - Cigarette smoking causes vascular endothelial dysfunction and is a major risk
      factor for cardiovascular diseases. Nicotine, a major constituent of cigarette
      smoke, has been shown to alter gene expression in endothelial cells; however, the
      regulatory pathways involved remain to be defined. We hypothesized that there
      might be distinct pathways that could be identified by systematic transcriptome
      analysis. Using the cDNA microarray approach, we ascertained the expression of
      over 4,000 genes in human coronary artery endothelial cells and identified a
      number of nicotine-modulated genes encoding a protein involving in signal
      transduction or transcriptional regulation. Among these were phosphatidylinositol
      phosphate kinase and diacylglycerol kinase, which are regulators of the inositol
      phospholipid pathway. Changes were also detected for transcription factors cAMP
      response element binding protein and nuclear factor-kappaB, of which the
      activities of both have been previously shown to be altered in nicotine
      stimulated cells. The data from this study are relevant to understanding the
      mechanisms underlying the pathophysiological effect of nicotine and smoking,
      particularly on endothelial function and pathogenesis of atherosclerosis.

PMID- 11328965
TI  - Nuclear transfer of adult and genetically modified fetal cells of the rat.
AB  - The present study examines the handling, activation, and micromanipulation of rat
      eggs in an attempt to produce live young using nuclear transfer (NT) of adult and
      genetically modified rat fetal cells. Mature rat eggs cultured in calcium-free
      medium showed reduced rates (24%) of chromosomal dispersion ("spontaneous
      activation" characteristic of this species) compared with eggs cultured in
      calcium-containing medium (47%), but failed to survive micromanipulation
      procedures. High rates of parthenogenetic cleavage were obtained with chemical
      activation using ethanol/cycloheximide (65%) compared with other standard
      chemical activation methods (4-28%). This type of activation was also effective
      in reestablishing cleavage capability (19-71%), in a time-dependent manner, of
      spontaneously activated eggs arrested at a second prophase-like state. At most,
      two of four tested micromanipulation procedures were effective in producing NT
      embryos capable of morula or blastocyst development (14-16%) in vivo following
      transfer to mouse oviducts. NT blastocysts produced from cumulus cells and
      transfected rat fetal fibroblasts appeared morphologically and karyotypically
      normal (2n = 42). Nocodazole-assisted metaphase enucleation and piezoelectric
      assisted donor cell injection produced significant and equivocal effects on
      survival and cleavage rates of reconstructed embryos but failed to significantly
      improve in vivo morula/blastocyst development rates (16-28%) compared with
      unassisted micromanipulation (16%). Live births have not yet been obtained from
      early cleavage stage embryos (n = 269) transferred to pseudopregnant recipient
      rat oviducts. Improvements in reconstituted NT embryo culture and transfer are
      required for these methods to be an effective means of transgenic rat production.

PMID- 11328966
TI  - Genetic loci determining bone density in mice with diet-induced atherosclerosis.
AB  - This study investigates the phenotypic and genetic relationships among bone
      density-related traits and those of adipose tissue and plasma lipids in mice with
      diet-induced atherosclerosis. Sixteen-month-old female F2 progeny of a C57BL/6J
      and DBA/2J intercross, which had received an atherogenic diet for 4 mo, were
      examined for multiple measures of femoral bone mass, density, and biomechanical
      properties using both computerized tomographic and radiographic methods. In
      addition, body weight and length, adipose tissue mass, plasma lipids and insulin,
      and aortic fatty lesions were assessed. Bone mass was inversely correlated with
      extent of atherosclerosis and with a prooxidant lipid profile and directly
      correlated with body weight, length, and, most strongly, adipose tissue mass.
      Quantitative trait locus (QTL) analysis, using composite interval mapping (CIM)
      and multi-trait analysis, identified six loci with multi-trait CIM LOD scores >
      5. Three of these coincided with loci linked with adipose tissue and plasma high
      density lipoprotein. Application of statistical tests for distinguishing close
      linkage vs. pleiotropy supported the presence of a potential pleiotropic effect
      of two of the loci on these traits. This study shows that bone mass in older
      female mice with atherosclerosis has multiple genetic determinants and provides
      phenotypic and genetic evidence linking the regulation of bone density with
      adipose tissue and plasma lipids.

PMID- 11328967
TI  - [Foetal medicine].
AB  - This paper deals with present possibilities in the field of diagnosis and
      prognosis of foetal malformations and developmental disturbances. Differential
      diagnosis of congenital malformations, including intrauterine growth retardation
      (IUGR), polyhydramnios and foetal hydrops is discussed on the basis of probable
      or suspected etiology. Indications for in-utero treatment, applicable only in a
      very limited and carefully selected number of cases, are considered. In the
      majority of severe cases of congenital malformations diagnosed prenatally, the
      only factors considered are: the optimal time and way of terminating pregnancy
      and the possibilities of therapeutic intervention after birth. The paediatrician 
      neonatologist plays an important role in a multidisciplinary team dealing with
      the diagnosis and treatment of congenital malformations.

PMID- 11328968
TI  - [Comparison of the early response to natural and synthetic surfactant in
      premature babies with respiratory distress syndrome].
AB  - OBJECTIVES: To compare the early response to natural and synthetic surfactant in
      premature babies with respiratory distress syndrome (RDS). METHODS: This is a
      prospective study of 21 newborns with respiratory distress syndrome treated with
      natural or synthetic surfactant. The response rapidity after administration of
      natural or synthetic surfactant was compared by parameters of mechanical
      ventilation (FiO2, Pmax, IO) in the first 6 hours and during the following 7 days
      of life. The frequency of respiratory complications, presence of patent ductus
      arteriosus (PDA) and its treatment and causes of death were evaluated. RESULTS:
      Definitely quicker decrease in ventilation parameters was observed after the
      administration of natural surfactant as compared to the synthetic one.
      Statistically significant differences were observed during 72 hours and then they
      decreased. CONCLUSION: The response after the administration of natural
      surfactants in premature babies with RDS within the first six hours of treatment
      was significantly quicker than after synthetic surfactant. This improves the
      parameters of mechanical ventilation much quicker and prevents complications.
      Longitudinal studies of the development of children treated with both kinds of
      surfactant are necessary in order to evaluate the effects of the treatment in the
      neonatal period.

PMID- 11328969
TI  - [Changes in the clinical picture of bronchopulmonary dysplasia].
AB  - The mortality of very preterm infants has significantly improved after
      introducing into clinical practice the antenatal use of glucocorticoid steroids
      prior to premature births and postnatal treatment with pulmonary surfactant which
      effectively decreases the tendency of the alveoli to collapse. The period of
      necessary mechanical ventilation was shortened. Reducing the concentration of
      inspired oxygen and inflation pressures became possible. In spite of this, long
      term damage of lung tissue in immature infants is still a major clinical problem.
      However, its origin seems to be slightly different. A new form of
      bronchopulmonary dysplasia (BPD) has been recently evaluated. The most important
      factors in the pathogenesis of the "new" BPD are: lung tissue immaturity,
      infections initiating a cascade of events caused by formation of free oxygen
      radicals and cytokines and the presence of persistent patent ductus arteriosus.
      Primary prevention of BPD is possible by reducing the rates of prematurity and
      intrauterine infections. Secondary prevention includes antenatal steroids
      administration and postnatal surfactant treatment according to the accepted known
      standards. When protracted mechanical ventilation is necessary, low and
      subsequently reduced doses of i.v. glucocorticoid steroids in the second and
      third week of life are administrated, together with diuretics, bronchodilators
      and suitably high calorie feeding.

PMID- 11328970
TI  - [Trophic feeding of very low birth weight infants].
AB  - The author presents current views on early trophic feeding of very low birth
      weight infants. Trophic feeding does not increase the risk of necrotizing
      enterocolitis, but sustains structural intestinal integrity, promotes maturation
      of gastrointestinal tract and decreases the complications of parenteral
      nutrition. Principles of initiating enteral feeding, contraindications and the
      most common problems accompanying enteral feeding were presented.

PMID- 11328971
TI  - [Ibuprofen--a new application for pharmacological closure of patent ductus
      arteriosus in preterm infants. Preliminary report].
AB  - Patent ductus arteriosus (PDA) remains a frequent problem in premature infants,
      particularly with very low birth weight. Left-to-right shunting through the
      ductus may increase the risk of intraventricular hemorrhage, necrotizing
      enterocolitis, bronchopulmonary dysplasia and death. Indomethacin is the
      conventional pharmacologic treatment of patent ductus arteriosus (PDA). Although
      indomethacin is effective in closing PDA, its use may be associated with negative
      influences on renal, gastrointestinal and cerebral blood flow. More recently
      Ibuprofen has been tested; it can close the ductus arteriosus, but compared it
      with indomethacin, it has no negative influence on intestinal haemodynamics. On
      the basis of relevant literature, ibuprofen and indomethacin have been compared
      with regard to efficacy for closure of patent ductus arteriosus and side effects.

PMID- 11328972
TI  - [Periventricular haemorrhagic infarction in prematurely born babies].
AB  - OBJECTIVES: Periventricular haemorrhagic infarction observed in premature infants
      is associated with intraventricular haemorrhage (IVH), which leads to obstruction
      of the terminal veins of periventricular white matter. This lesion has
      characteristic ultrasonographic evolution. The objectives of this study were to
      determine the frequency of occurrence of periventricular haemorrhagic infarction
      in premature infants in intensive care unit and to evaluate the risk factors.
      METHODS: A total of 203 premature infants weighing less then 1500 g at birth
      underwent standardized cranial ultrasound between November 1997 and June 2000.
      RESULTS: A total of 156 premature infants with VLBW and ELBW had IVH of various
      degree and 17 (8,4%) had periventricular haemorrhagic infarction (PHI). 14 babies
      with PHI died. Among the survivors, 2 exhibit spastic hemiparesis and one had
      signs of tetraplegia at 6 months of age. CONCLUSIONS: This study indicates, that
      PHI occurs more often in neonates, who required a lot of volume expansion due to
      systemic hypotension. Antenatal glucocorticoid administration has a protective
      function.

PMID- 11328973
TI  - [Clinical and laboratory diagnosis of Listeria monocytogenes on the basis of own
      investigations].
AB  - The authors have described the issues surrounding Listeria monocytogenes
      infection with reference to cases diagnosed and managed during the 5-year period
      (1995-2000) in the Clinical Department of Neonatal Pathology and Intensive Care
      of the National Institute of Mother and Child in Warsaw. Four cases of congenital
      listeriosis have been diagnosed. Some mothers presented with "flu-like" symptoms.
      All mothers delivered prematurely (29 hbd - 32 hbd). Among the 4 infants the most
      common clinical features were: perinatal asphyxia, respiratory distress,
      pathological icterus, haematologic abnormalities. Septicemia occurred in 50% of
      cases; pneumonia in 100%. Three of them presented skin manifestations; one of the
      neonates had mucosal abnormalities of the laryngopharynx. Cerebral sonography
      showed intracranial hemorrhage. One of the infants died within 7 days of birth.
      The other two neonates developed posthemorrhagic hydrocephalus. Only one infant
      has normal development. Although listeriosis appears to be not a frequent cause
      of perinatal infection, clinicians must be aware of Listeria, particularly in
      gravid patients who present with fever and "flu-like" illness and go into
      premature labour. Initial therapy implemented in our Department, with ampicillin
      and aminoglycosides seem to be the most appropriate.

PMID- 11328974
TI  - [Study of the effectiveness of clinical risk index for babies].
AB  - The aim of the study was to assess the effectiveness of the clinical risk index
      (CRIB) for the prognosis survival of newborns with low birth weight. The examined
      group consisted of 69 newborns who were admitted to the Clinical Department of
      Neonatal Pathology and Intensive Care at the National Institute of Mother and
      Child in Warsaw. The newborn babies were of less than 31 Hbd gestational age and
      less than 1501 g birth weight. The group of newborns was divided into 3 subgroups
      according to the level of the CRIB index. Gestational age, birth weight, Apgar
      score, use of prenatal steroids, introduction of surfactant supply and newborn
      survival were estimated. The CRIB score proved to be useful in anticipating the
      survival of newborns with critically low birth weight. The higher the CRIB score,
      the lower was the expectation for survival. The close relation of the CRIB score
      with gestational age, birth weight and Apgar score was proved. The indication for
      introduction of surfactant depends both on the newborn's clinical condition and
      on the CRIB score as well.

PMID- 11328975
TI  - [The "Kangaroo" ward].
AB  - The "Kangaroo mother" is a symbol of gentle care for the newborn in continuous
      closeness with his/her mother. This concept was for the first time introduced to
      neonatal care in Columbia as a way of compensating for technical and personnel
      shortages. In France, the first Kangaroo ward was established in the academic
      hospital in Clamart, near Paris in 1987. This ward is designed for premature
      babies of gestational age of more than 31 weeks and with birth weight more than
      1500 g as well as for newborns with non-life threatening conditions and not
      requiring intensive care. Handling the child, skin-to-skin contact and breast
      feeding are not treated as therapeutic means but as important elements of the
      relationship between the child and his/her parents. The author discusses in
      detail the organisation of care in the Kangaroo ward and analyses its advantages
      and disadvantages for both parents and the medical staff. Apart from providing
      continuous contact between the mother and the child, the important advantages of
      this system of care are: less maternal anxiety, well-being of the child, more
      efficient participation of mothers in caring for their children. The role of the
      paediatrician in perinatal care is stressed and the principles of neonatal
      organisation are discussed.

PMID- 11328976
TI  - [Parents and their prematurely born child--from experience of cooperation of a
      psychologist with the clinical department of neonatal pathology and intensive
      care].
AB  - PROBLEM: Premature birth and hospitalisation of a child in the first weeks of
      life may have a potentially adverse effect on the relationship between the
      parents and the child. AIM: The aim of this paper is to describe: 1) emotional
      reactions of parents of babies born prematurely, 2) parental processes of coping,
      and 3) psychological intervention in the context of tertiary care hospital ward.
      DESCRIPTION: The author presents data from relevant literature and her clinical
      experiences of co-operation with the Clinical Department of Neonatal Pathology
      and Intensive Care of the National Research Institute of Mother and Child in
      Warsaw. CONCLUSIONS: Parents of premature neonates experience a whole range of
      emotional reactions and use different ways of coping. Psychological intervention
      in the post-partum period is aimed at preventing disorders of bonding and
      attachment.

PMID- 11328977
TI  - [Program of early stimulation and developmental care in the newborn. Role and
      tasks of the physiotherapist].
AB  - Early stimulation and developmental care programme should be applied in all high
      risk neonates. Special care is needed in children born prematurely and with low
      and very low birth weight. The aim of this paper is to specify the requirements
      for optimal conditions of psychomotor development of a child in the neonatal
      intensive care unit NICU environment.

PMID- 11328978
TI  - Metal bashing.

PMID- 11328979
TI  - Surviving another slump.

PMID- 11328980
TI  - Financing falters, biotechnology shares deflate in 2001.

PMID- 11328981
TI  - US Supreme Court decision could compromise biotech patents.

PMID- 11328982
TI  - PDL's mAb technology finds right timing.

PMID- 11328984
TI  - Euro biotech report adds to paper mountain.

PMID- 11328983
TI  - Canadian farmer found guilty of Monsanto canola patent infringement.

PMID- 11328985
TI  - Big pharmas seek biotechs that deliver.

PMID- 11328996
TI  - The parts list of life.

PMID- 11328997
TI  - Cloning and genetic determinism--a call for consistency.

PMID- 11328998
TI  - The limits of GMO detection.

PMID- 11328999
TI  - Cloning efficiency and differentiation.

PMID- 11329000
TI  - Public biotech 2000--the numbers.

PMID- 11329001
TI  - Sense versus nonsense in DNA diagnostics.

PMID- 11329002
TI  - Phosphorus-friendly transgenics.

PMID- 11329003
TI  - Improving rice yields--ironing out the details.

PMID- 11329004
TI  - Searching for array standards in Rockville.

PMID- 11329010
TI  - Directed evolution of proteins by exon shuffling.
AB  - Evolution of eukaryotes is mediated by sexual recombination of parental genomes.
      Crossovers occur in random, but homologous, positions at a frequency that depends
      on DNA length. As exons occupy only 1% of the human genome and introns about 24%,
      by far most of the crossovers occur between exons, rather than inside. The
      natural process of creating new combinations of exons by intronic recombination
      is called exon shuffling. Our group is developing in vitro formats for exon
      shuffling and applying these to the directed evolution of proteins. Based on the
      splice frame junctions, nine classes of exons and three classes of introns can be
      distinguished. Splice frame diagrams of natural genes show how the splice frame
      rules govern exon shuffling. Here, we review various approaches to constructing
      libraries of exon-shuffled genes. For example, exon shuffling of human
      pharmaceutical proteins can generate libraries in which all of the sequences are
      fully human, without the point mutations that raise concerns about
      immunogenicity.

PMID- 11329011
TI  - Transgenic mice expressing bacterial phytase as a model for phosphorus pollution
      control.
AB  - We have developed transgenic mouse models to determine whether endogenous
      expression of phytase transgenes in the digestive tract of monogastric animals
      can increase the bioavailability of dietary phytate, a major but indigestible
      form of dietary phosphorus. We constructed phytase transgenes composed of the
      appA phytase gene from Escherichia coli regulated for expression in salivary
      glands by the rat R15 proline-rich protein promoter or by the mouse parotid
      secretory protein promoter. Transgenic phytase is highly expressed in the parotid
      salivary glands and secreted in saliva as an enzymatically active 55 kDa
      glycosylated protein. Expression of salivary phytase reduces fecal phosphorus by
      11%. These results suggest that the introduction of salivary phytase transgenes
      into monogastric farm animals offers a promising biological approach to relieving
      the requirement for dietary phosphate supplements and to reducing phosphorus
      pollution from animal agriculture.

PMID- 11329012
TI  - A strategy for disease gene identification through nonsense-mediated mRNA decay
      inhibition.
AB  - Premature termination codons (PTCs) have been shown to initiate degradation of
      mutant transcripts through the nonsense-mediated messenger RNA (mRNA) decay (NMD)
      pathway. We report a strategy, termed gene identification by NMD inhibition
      (GINI), to identify genes harboring nonsense codons that underlie human diseases.
      In this strategy, the NMD pathway is pharmacologically inhibited in cultured
      patient cells, resulting in stabilization of nonsense transcripts. To distinguish
      stabilized nonsense transcripts from background transcripts upregulated by drug
      treatment, drug-induced expression changes are measured in control and disease
      cell lines with complementary DNA (cDNA) microarrays. Transcripts are ranked by a
      nonsense enrichment index (NEI), which relates expression changes for a given
      transcript in NMD-inhibited control and patient cell lines. The most promising
      candidates can be selected using information such as map location or biological
      function; however, an important advantage of the GINI strategy is that a priori
      information is not essential for disease gene identification. GINI was tested on
      colon cancer and Sandhoff disease cell lines, which contained previously
      characterized nonsense mutations in the MutL homolog 1 (MLH1) and hexosaminidase
      B (HEXB) genes, respectively. A list of genes was produced in which the MLH1 and
      HEXB genes were among the top 1% of candidates, thus validating the strategy.

PMID- 11329013
TI  - Creation of genome-wide protein expression libraries using random activation of
      gene expression.
AB  - Here we report the use of random activation of gene expression (RAGE) to create
      genome-wide protein expression libraries. RAGE libraries containing only 5 x
      10(6) individual clones were found to express every gene tested, including genes
      that are normally silent in the parent cell line. Furthermore, endogenous genes
      were activated at similar frequencies and expressed at similar levels within RAGE
      libraries created from multiple human cell lines, demonstrating that RAGE
      libraries are inherently normalized. Pools of RAGE clones were used to isolate
      19,547 human gene clusters, approximately 53% of which were novel when tested
      against public databases of expressed sequence tag (EST) and complementary DNA
      (cDNA). Isolation of individual clones confirmed that the activated endogenous
      genes can be expressed at high levels to produce biologically active proteins.
      The properties of RAGE libraries and RAGE expression clones are well suited for a
      number of biotechnological applications including gene discovery, protein
      characterization, drug development, and protein manufacturing.

PMID- 11329014
TI  - The HIV-1 DNA flap stimulates HIV vector-mediated cell transduction in the brain.
AB  - During HIV-1 reverse transcription, central initiation of the plus-strand DNA at
      the central polypurine tract (cPPT) and central termination at the central
      termination sequence (CTS) lead to the formation of a three-stranded DNA
      structure: the HIV-1 central DNA flap. We recently reported that the DNA flap
      acts as a cis-active determinant of HIV-1 genome nuclear import. Commonly
      employed HIV-1-derived vectors (HR vectors) lack the central DNA flap. Here we
      report that the insertion of this DNA flap sequence into HR vectors (TRIP
      vectors) improves gene transduction in neural cells, ex vivo and in vivo, in rat
      brain. When neural cells are exposed to increasing concentrations of TRIP vector
      particles, transgene expression correlates with the dose of vector. This effect
      contrasts with the plateau observed when using an HR vector. We further
      demonstrate that the increase of in vivo transduction efficiency obtained with
      TRIP vectors is due to the stimulation of their genome nuclear import.

PMID- 11329015
TI  - Incorporation of decay-accelerating factor into the baculovirus envelope
      generates complement-resistant gene transfer vectors.
AB  - Baculovirus vectors are an efficient means to deliver genes into hepatocytes in
      vitro. In experiments that exclude components of the complement system, gene
      transfer is facilitated. Therefore, the complement system has been defined to
      represent a potent primary barrier to direct application of baculoviruses in
      vivo. Here we have genetically manipulated baculoviruses so that the complement
      regulatory protein human decay- accelerating factor (DAF) is incorporated into
      the viral envelope. We found that this modification protected baculovirus vectors
      against complement-mediated inactivation. Complement-resistant baculovirus
      vectors were additionally analyzed by immunoblotting and electron microscopy,
      showing the extent of envelope-incorporated DAF and shape of complement-resistant
      baculoviruses after exposure to complement. This modified baculovirus vector
      allowed for an enhanced gene transfer into complement-sufficient neonatal rats in
      vivo, and thus represents a step in the development of improved alternative viral
      vectors for gene therapy.

PMID- 11329016
TI  - Libraries of hybrid proteins from distantly related sequences.
AB  - We introduce a method for sequence homology-independent protein recombination
      (SHIPREC) that can create libraries of single-crossover hybrids of unrelated or
      distantly related proteins. The method maintains the proper sequence alignment
      between the parents and introduces crossovers mainly at structurally related
      sites distributed over the aligned sequences. We used SHIPREC to create a library
      of interspecies hybrids of a membrane-associated human cytochrome P450 (1A2) and
      the heme domain of a soluble bacterial P450 (BM3). By fusing the hybrid gene
      library to the gene for chloramphenicol acetyl transferase (CAT), we were able to
      select for soluble and properly folded protein variants. Screening for 1A2
      activity (deethylation of 7-ethoxyresorufin) identified two functional P450
      hybrids that were more soluble in the bacterial cytoplasm than the wild-type 1A2
      enzyme.

PMID- 11329017
TI  - A rapid diffusion immunoassay in a T-sensor.
AB  - We have developed a rapid diffusion immunoassay that allows measurement of small
      molecules down to subnanomolar concentrations in <1 min. This competitive assay
      is based on measuring the distribution of a labeled probe molecule after it
      diffuses for a short time from one region into another region containing antigen
      specific antibodies. The assay was demonstrated in the T-sensor, a simple
      microfluidic device that places two fluid streams in contact and allows
      interdiffusion of their components. The model analyte was phenytoin, a typical
      small drug molecule. Clinically relevant levels were measured in blood diluted
      from 10- to 400-fold in buffer containing the labeled antigen. Removal of cells
      from blood samples was not necessary. This assay compared favorably with
      fluorescence polarization immunoassay (FPIA) measurements. Numerical simulations
      agree well with experimental results and provide insight for predicting assay
      performance and limitations. The assay is homogeneous, requires <1 microl of
      reagents and sample, and is applicable to a wide range of analytes.

PMID- 11329018
TI  - Enhanced tolerance of rice to low iron availability in alkaline soils using
      barley nicotianamine aminotransferase genes.
AB  - One of the widest ranging abiotic stresses in world agriculture arises from low
      iron (Fe) availability due to high soil pH, with 30% of arable land too alkaline
      for optimal crop production. Rice is especially susceptible to low iron supply,
      whereas other graminaceous crops such as barley are not. A barley genomic DNA
      fragment containing two naat genes, which encode crucial enzymes involved in the
      biosynthesis of phytosiderophores, was introduced into rice using Agrobacterium
      mediated transformation and pBIGRZ1. Phytosiderophores are natural iron chelators
      that graminaceous plants secrete from their roots to solubilize iron in the soil.
      The two transgenes were expressed in response to low iron nutritional status in
      both the shoots and roots of rice transformants. Transgenic rice expressing the
      two genes showed a higher nicotianamine aminotransferase activity and secreted
      larger amounts of phytosiderophores than nontransformants under iron-deficient
      conditions. Consequently, the transgenic rice showed an enhanced tolerance to low
      iron availability and had 4.1 times greater grain yields than that of the
      nontransformant rice in an alkaline soil.

PMID- 11329020
TI  - Growth factors regulate the survival and fate of cells derived from human
      neurospheres.
AB  - Cells isolated from the embryonic, neonatal, and adult rodent central nervous
      system divide in response to epidermal growth factor (EGF) and fibroblast growth
      factor 2 (FGF-2), while retaining the ability to differentiate into neurons and
      glia. These cultures can be grown in aggregates termed neurospheres, which
      contain a heterogeneous mix of both multipotent stem cells and more restricted
      progenitor populations. Neurospheres can also be generated from the embryonic
      human brain and in some cases have been expanded for extended periods of time in
      culture. However, the mechanisms controlling the number of neurons generated from
      human neurospheres are poorly understood. Here we show that maintaining cell-cell
      contact during the differentiation stage, in combination with growth factor
      administration, can increase the number of neurons generated under serum-free
      conditions from 8% to > 60%. Neurotrophic factors 3 and 4 (NT3, NT4) and platelet
      derived growth factor (PDGF) were the most potent, and acted by increasing
      neuronal survival rather than inducing neuronal phenotype. Following
      differentiation, the neurons could survive dissociation and either replating or
      transplantation into the adult rat brain. This experimental system provides a
      practically limitless supply of enriched, non-genetically transformed neurons.
      These should be useful for both neuroactive drug screening in vitro and possibly
      cell therapy for neurodegenerative diseases.

PMID- 11329019
TI  - Overexpression of petunia chalcone isomerase in tomato results in fruit
      containing increased levels of flavonols.
AB  - Tomatoes are an excellent source of the carotenoid lycopene, a compound that is
      thought to be protective against prostate cancer. They also contain small amounts
      of flavonoids in their peel ( approximately 5-10 mg/kg fresh weight), mainly
      naringenin chalcone and the flavonol rutin, a quercetin glycoside. Flavonols are
      very potent antioxidants, and an increasing body of epidemiological data suggests
      that high flavonoid intake is correlated with a decreased risk for cardiovascular
      disease. We have upregulated flavonol biosynthesis in the tomato in order to
      generate fruit with increased antioxidant capacity and a wider range of potential
      health benefit properties. This involved transformation of tomato with the
      Petunia chi-a gene encoding chalcone isomerase. Resulting transgenic tomato lines
      produced an increase of up to 78 fold in fruit peel flavonols, mainly due to an
      accumulation of rutin. No gross phenotypical differences were observed between
      high-flavonol transgenic and control lines. The phenotype segregated with the
      transgene and demonstrated a stable inheritance pattern over four subsequent
      generations tested thus far. Whole-fruit flavonol levels in the best of these
      lines are similar to those found in onions, a crop with naturally high levels of
      flavonol compounds. Processing of high-flavonol tomatoes demonstrated that 65% of
      flavonols present in the fresh fruit were retained in the processed paste,
      supporting their potential as raw materials for tomato-based functional food
      products.

PMID- 11329021
TI  - Methods of treatment: is there any protection available in Europe?

PMID- 11329026
TI  - Hope in the modern plague.

PMID- 11329027
TI  - Transplanted dopaminergic neurons: more or less?

PMID- 11329029
TI  - South Africa releases controversial AIDS panel report.

PMID- 11329030
TI  - Resistance study to re-evaluate HAART.

PMID- 11329031
TI  - Harvard docs pitch global AIDS drug program.

PMID- 11329032
TI  - Cash invigorates European AIDS study.

PMID- 11329033
TI  - First sepsis drug nears market.

PMID- 11329035
TI  - PCs enlisted to cure cancer.

PMID- 11329036
TI  - US still lacks human cloning legislation.

PMID- 11329041
TI  - Elizabeth Blackburn.

PMID- 11329042
TI  - A new global commitment to disease control in Africa.
AB  - Despite the availability of effective therapies in developed nations, infectious
      diseases continue to take a grave toll on the population and economy of sub
      Saharan Africa. Aside from a few successes, the global donor community has not
      adequately helped African governments meet these health challenges. However, if
      annual donor contributions increased approximately 10-20-fold, millions of lives
      could be saved, helping Africa escape the cycle of disease and impoverishment.

PMID- 11329045
TI  - Inflammation and Alzheimer disease: the good, the bad, and the ugly.

PMID- 11329046
TI  - Polyglutamine and CBP: fatal attraction?

PMID- 11329047
TI  - TREM-1: a new regulator of innate immunity in sepsis syndrome.

PMID- 11329048
TI  - The well-tempered vessel.

PMID- 11329049
TI  - Inhaled CO: deadly gas or novel therapeutic?

PMID- 11329050
TI  - Promiscuous regulator of xenobiotic removal.

PMID- 11329051
TI  - VIP: a very important protein in arthritis.

PMID- 11329053
TI  - The cellular neurobiology of depression.
AB  - Major depressive disorders, long considered to be of neurochemical origin, have
      recently been associated with impairments in signaling pathways that regulate
      neuroplasticity and cell survival. Agents designed to directly target molecules
      in these pathways may hold promise as new therapeutics for depression.

PMID- 11329054
TI  - Molecular targets for breast cancer therapy and prevention.
AB  - The recent completion of the human genome sequence has raised great hopes for the
      discovery of new breast cancer therapies based on newly-discovered genes linked
      to breast cancer development and progression. Here we describe breast cancer
      therapies that have emerged from gene-based scientific efforts over the past 20
      years and that are now approved for clinical testing or treatment.

PMID- 11329055
TI  - Breast cancer genetics: what we know and what we need.
AB  - Breast cancer results from genetic and environmental factors leading to the
      accumulation of mutations in essential genes. Genetic predisposition may have a
      strong, almost singular effect, as with BRCA1 and BRCA2, or may represent the
      cumulative effects of multiple low-penetrance susceptibility alleles. Here we
      review high- and low-penetrance breast-cancer-susceptibility alleles and discuss
      ongoing efforts to identify additional susceptibility genes. Ultimately these
      discoveries will lead to individualized breast cancer risk assessment and a
      reduction in breast cancer incidence.

PMID- 11329056
TI  - Inhibition of natural killer cells results in acceptance of cardiac allografts in
      CD28-/- mice.
AB  - Successful transplantation of allogeneic organs is an important objective in
      modern medicine. However, sophisticated immune defense mechanisms, primarily
      evolved to combat infections, often work against medical transplantation. To
      investigate the roles of natural and adaptive immune responses in transplant
      rejection, we functionally inactivated key effector systems of the innate (NK
      cells) and the adaptive immune system (CD28-mediated costimulation of T cells) in
      mice. Neither of these interventions alone led to acceptance of allogeneic
      vascularized cardiac grafts. In contrast, inhibition of NK-receptor-bearing cells
      combined with CD28-costimulation blockade established long-term graft acceptance.
      These results indicate a concerted interplay between innate and adaptive immune
      surveillance for graft rejection. Thus we suggest that inactivation of NK
      receptor-bearing cells could be a new strategy for successful survival of solid
      organ transplants.

PMID- 11329057
TI  - Vasoactive intestinal peptide prevents experimental arthritis by downregulating
      both autoimmune and inflammatory components of the disease.
AB  - Rheumatoid arthritis (RA) is a chronic and debilitating autoimmune disease of
      unknown etiology, characterized by chronic inflammation in the joints and
      subsequent destruction of the cartilage and bone. We describe here a new strategy
      for the treatment of arthritis: administration of the neuropeptide vasoactive
      intestinal peptide (VIP). Treatment with VIP significantly reduced incidence and
      severity of arthritis in an experimental model, completely abrogating joint
      swelling and destruction of cartilage and bone. The therapeutic effect of VIP was
      associated with downregulation of both inflammatory and autoimmune components of
      the disease. Our data indicate VIP as a viable candidate for the development of
      treatments for RA.

PMID- 11329058
TI  - The neurotransmitter dopamine inhibits angiogenesis induced by vascular
      permeability factor/vascular endothelial growth factor.
AB  - Angiogenesis has an essential role in many important pathological and
      physiological settings. It has been shown that vascular permeability
      factor/vascular endothelial growth factor (VPF/VEGF), a potent cytokine expressed
      by most malignant tumors, has critical roles in vasculogenesis and both
      physiological and pathological angiogenesis. We report here that at non-toxic
      levels, the neurotransmitter dopamine strongly and selectively inhibited the
      vascular permeabilizing and angiogenic activities of VPF/VEGF. Dopamine acted
      through D2 dopamine receptors to induce endocytosis of VEGF receptor 2, which is
      critical for promoting angiogenesis, thereby preventing VPF/VEGF binding,
      receptor phosphorylation and subsequent signaling steps. The action of dopamine
      was specific for VPF/VEGF and did not affect other mediators of microvascular
      permeability or endothelial-cell proliferation or migration. These results reveal
      a new link between the nervous system and angiogenesis and indicate that dopamine
      and other D2 receptors, already in clinical use for other purposes, might have
      value in anti-angiogenesis therapy.

PMID- 11329059
TI  - Synergism between vascular endothelial growth factor and placental growth factor
      contributes to angiogenesis and plasma extravasation in pathological conditions.
AB  - Vascular endothelial growth factor (VEGF) stimulates angiogenesis by activating
      VEGF receptor-2 (VEGFR-2). The role of its homolog, placental growth factor
      (PlGF), remains unknown. Both VEGF and PlGF bind to VEGF receptor-1 (VEGFR-1),
      but it is unknown whether VEGFR-1, which exists as a soluble or a membrane-bound
      type, is an inert decoy or a signaling receptor for PlGF during angiogenesis.
      Here, we report that embryonic angiogenesis in mice was not affected by
      deficiency of PlGF (Pgf-/-). VEGF-B, another ligand of VEGFR-1, did not rescue
      development in Pgf-/- mice. However, loss of PlGF impaired angiogenesis, plasma
      extravasation and collateral growth during ischemia, inflammation, wound healing
      and cancer. Transplantation of wild-type bone marrow rescued the impaired
      angiogenesis and collateral growth in Pgf-/- mice, indicating that PlGF might
      have contributed to vessel growth in the adult by mobilizing bone-marrow-derived
      cells. The synergism between PlGF and VEGF was specific, as PlGF deficiency
      impaired the response to VEGF, but not to bFGF or histamine. VEGFR-1 was
      activated by PlGF, given that anti-VEGFR-1 antibodies and a Src-kinase inhibitor
      blocked the endothelial response to PlGF or VEGF/PlGF. By upregulating PlGF and
      the signaling subtype of VEGFR-1, endothelial cells amplify their responsiveness
      to VEGF during the 'angiogenic switch' in many pathological disorders.

PMID- 11329060
TI  - The orphan nuclear receptor SXR coordinately regulates drug metabolism and
      efflux.
AB  - Cytochrome P450 3A4 is an important mediator of drug catabolism that can be
      regulated by the steroid and xenobiotic receptor (SXR). We show here that SXR
      also regulates drug efflux by activating expression of the gene MDR1, which
      encodes the protein P-glycoprotein (ABCB1). Paclitaxel (Taxol), a commonly used
      chemotherapeutic agent, activated SXR and enhanced P-glycoprotein-mediated drug
      clearance. In contrast, docetaxel (Taxotere), a closely related antineoplastic
      agent, did not activate SXR and displayed superior pharmacokinetic properties.
      Docetaxel's silent properties reflect its inability to displace transcriptional
      corepressors from SXR. We also found that ET-743, a potent antineoplastic agent,
      suppressed MDR1 transcription by acting as an inhibitor of SXR. These findings
      demonstrate how the molecular activities of SXR can be manipulated to control
      drug clearance.

PMID- 11329061
TI  - Adult mice deficient in actinin-associated LIM-domain protein reveal a
      developmental pathway for right ventricular cardiomyopathy.
AB  - Although cytoskeletal mutations are known causes of genetically based forms of
      dilated cardiomyopathy, the pathways that link these defects with cardiomyopathy
      are unclear. Here we report that the alpha-actinin-associated LIM protein (ALP;
      Alp in mice) has an essential role in the embryonic development of the right
      ventricular (RV) chamber during its exposure to high biomechanical workloads in
      utero. Disruption of the gene encoding Alp (Alp) is associated with RV chamber
      dilation and dysfunction, directly implicating alpha-actinin-associated proteins
      in the onset of cardiomyopathy. In vitro assays showed that Alp directly enhances
      the capacity of alpha-actinin to cross-link actin filaments, indicating that the
      loss of Alp function contributes to destabilization of actin anchorage sites in
      cardiac muscle. Alp also colocalizes at the intercalated disc with alpha-actinin
      and gamma-catenin, the latter being a known disease gene for human RV dysplasia.
      Taken together, these studies point to a novel developmental pathway for RV
      dilated cardiomyopathy via instability of alpha-actinin complexes.

PMID- 11329062
TI  - Paradoxical rescue from ischemic lung injury by inhaled carbon monoxide driven by
      derepression of fibrinolysis.
AB  - Carbon monoxide (CO) can arrest cellular respiration, but paradoxically, it is
      synthesized endogenously by heme oxygenase type 1 (Ho-1) in response to ischemic
      stress. Ho-1-deficient (Hmox1-/-) mice exhibited lethal ischemic lung injury, but
      were rescued from death by inhaled CO. CO drove ischemic protection by activating
      soluble guanylate cyclase and thereby suppressed hypoxic induction of the gene
      encoding plasminogen activator inhibitor-1 (PAI-1) in mononuclear phagocytes,
      which reduced accrual of microvascular fibrin. CO-mediated ischemic protection
      observed in wild-type mice was lost in mice null for the gene encoding PAI-1
      (Serpine1). These data establish a fundamental link between CO and prevention of
      ischemic injury based on the ability of CO to derepress the fibrinolytic axis.
      These data also point to a potential therapeutic use for inhaled CO.

PMID- 11329063
TI  - Human stresscopin and stresscopin-related peptide are selective ligands for the
      type 2 corticotropin-releasing hormone receptor.
AB  - Adaptive stress responses mediated by the endocrine, autonomic, cardiovascular
      and immune systems are essential for the survival of the individual. Initial
      stress-induced responses provide a vital short-term metabolic lift, but prolonged
      or inappropriate exposure to stress can compromise homeostasis thereby leading to
      disease. This 'fight-or-flight' response is characterized by the activation of
      the corticotropin-releasing hormone (CRH)-adrenocorticotropin-glucocorticoid
      axis, mediated by the type 1 CRH receptor. In contrast, the type 2 CRH receptor
      mediates the stress-coping responses during the recovery phase of stress. We
      identified human stresscopin (SCP) and stresscopin-related peptide (SRP) as
      specific ligands for the type 2 CRH receptor. The genes encoding these peptides
      were expressed in diverse peripheral tissues as well as in the central nervous
      system. Treatment with SCP or SRP suppressed food intake, delayed gastric
      emptying and decreased heat-induced edema. Thus SCP and SRP might represent
      endogenous ligands for maintaining homeostasis after stress, and could allow the
      design of drugs to ameliorate stress-related diseases.

PMID- 11329064
TI  - TGF-beta1 promotes microglial amyloid-beta clearance and reduces plaque burden in
      transgenic mice.
AB  - Abnormal accumulation of the amyloid-beta peptide (Abeta) in the brain appears
      crucial to pathogenesis in all forms of Alzheimer disease (AD), but the
      underlying mechanisms in the sporadic forms of AD remain unknown. Transforming
      growth factor beta1 (TGF-beta1), a key regulator of the brain's responses to
      injury and inflammation, has been implicated in Abeta deposition in vivo. Here we
      demonstrate that a modest increase in astroglial TGF-beta1 production in aged
      transgenic mice expressing the human beta-amyloid precursor protein (hAPP)
      results in a three-fold reduction in the number of parenchymal amyloid plaques, a
      50% reduction in the overall Abeta load in the hippocampus and neocortex, and a
      decrease in the number of dystrophic neurites. In mice expressing hAPP and TGF
      beta1, Abeta accumulated substantially in cerebral blood vessels, but not in
      parenchymal plaques. In human cases of AD, Abeta immunoreactivity associated with
      parenchymal plaques was inversely correlated with Abeta in blood vessels and
      cortical TGF-beta1 mRNA levels. The reduction of parenchymal plaques in hAPP/TGF
      beta1 mice was associated with a strong activation of microglia and an increase
      in inflammatory mediators. Recombinant TGF-beta1 stimulated Abeta clearance in
      microglial cell cultures. These results demonstrate that TGF-beta1 is an
      important modifier of amyloid deposition in vivo and indicate that TGF-beta1
      might promote microglial processes that inhibit the accumulation of Abeta in the
      brain parenchyma.

PMID- 11329065
TI  - Hepatitis-B virus endemicity: heterogeneity, catastrophic dynamics and control.
AB  - Hepatitis-B virus infection is globally ubiquitous, but its distribution is very
      heterogeneous, with prevalence of serological markers in various nations ranging
      from less than 1% to more than 90%. We propose an explanation for this diversity
      using a mathematical model of hepatitis-B virus transmission dynamics that shows,
      for the first time, 'catastrophic' behavior using realistic epidemiological
      processes and parameters. Our major conclusion is that the prevalence of
      infection is largely determined by a feedback mechanism that relates the rate of
      transmission, average age at infection and age-related probability of developing
      carriage following infection. Using the model we identify possible, highly non
      linear, consequences of chemotherapy and immunization interventions, for which
      the starting prevalence of carriers is the most influential, predictive quantity.
      Taken together, our results demand a re-evaluation of public health policy
      towards hepatitis-B.

PMID- 11329066
TI  - Whole recombinant yeast vaccine activates dendritic cells and elicits protective
      cell-mediated immunity.
AB  - There is currently a need for vaccines that stimulate cell-mediated immunity
      particularly that mediated by CD8+ cytotoxic T lymphocytes (CTLs)-against viral
      and tumor antigens. The optimal induction of cell-mediated immunity requires the
      presentation of antigens by specialized cells of the immune system called
      dendritic cells (DCs). DCs are unique in their ability to process exogenous
      antigens via the major histocompatibility complex (MHC) class I pathway as well
      as in their ability to activate naive, antigen-specific CD8+ and CD4+ T cells.
      Vaccine strategies that target or activate DCs in order to elicit potent CTL
      mediated immunity are the subject of intense research. We report here that whole
      recombinant Saccharomyces cerevisiae yeast expressing tumor or HIV-1 antigens
      potently induced antigen-specific, CTL responses, including those mediating tumor
      protection, in vaccinated animals. Interactions between yeast and DCs led to DC
      maturation, IL-12 production and the efficient priming of MHC class I- and class
      II-restricted, antigen-specific T-cell responses. Yeast exerted a strong adjuvant
      effect, augmenting DC presentation of exogenous whole-protein antigen to MHC
      class I- and class II-restricted T cells. Recombinant yeast represent a novel
      vaccine strategy for the induction of broad-based cellular immune responses.

PMID- 11329072
TI  - Progress in medicine and biology in the last centuries.

PMID- 11329067
TI  - A quantitative assay for HIV DNA integration in vivo.
AB  - Early steps of infection by HIV-1 involve entry of the viral core into cells,
      reverse transcription to form the linear viral DNA, and integration of that DNA
      into a chromosome of the host. The unintegrated DNA can also follow non
      productive pathways, in which it is circularized by recombination between DNA
      long-terminal repeats (LTRs), circularized by ligation of the DNA ends or
      degraded. Here we report quantitative methods that monitor formation of reverse
      transcription products, two-LTR circles and integrated proviruses. The
      integration assay employs a novel quantitative form of Alu-PCR that should be
      generally applicable to studies of integrating viruses and gene transfer vectors.

PMID- 11329073
TI  - Regenerative and plastic insufficiency of cardiomyocytes during impairment of
      protein synthesis.
AB  - Regenerative and plastic insufficiency of cardiomyocytes comprises cell changes
      resulting from impaired DNA-dependent RNA synthesis and biosynthetic processes.
      It is accompanied by progressive involution of cytoplasmic structures and causes
      atrophy and partial elimination of cells without signs of coagulation and
      colliquative necroses. Segregation and fragmentation of nucleoli in cardiomyocyte
      nuclei, lysis of myofibrils, and focal degradation of the cytoplasm are
      ultrastructural signs of impaired protein synthesis. Intracellular cardiomyocyte
      regeneration is characterized by disorientation of newly formed myofibrils and
      their excessive elongation, which are related to DNA damages followed by changes
      in transcription and translation in cardiomyocytes. Calculation of the absolute
      number of cardiomyocytes is a new approach to evaluation of contractile
      myocardial insufficiency.

PMID- 11329074
TI  - From neuroendocrinology to neuroimmunoendocrinology.

PMID- 11329075
TI  - Antisperm antibodies and sterility: insoluble problem or perspective trend of
      research?
AB  - Conflicting opinions about the effects of antisperm antibodies on fertilization
      can be due to inadequacy of experimental approaches in evaluating the antisperm
      immunity. Detection of antisperm antibodies bound to the surface of live
      spermatozoa can be associated with aggregation of surface antigen-antibody
      complexes followed by metabolic activation of spermatozoa and acrosomal reaction,
      which impair cell resistance. New concept of antisperm immunity and its influence
      on reproduction can be formulated only after comprehensive studies of the
      mechanisms of spermatozoon response to binding of antisperm antibodies. Further
      improvement of quantitative assays of antisperm antibodies and evaluation of
      their effect on spermatozoon function should be aimed at selection of
      experimental conditions preventing changes in spermatozoa coated with antisperm
      antibodies during in vitro manipulations.

PMID- 11329076
TI  - Prooxidant-antioxidant state after administration of lipopolysaccharide during
      correction of the L-arginine-NO system and affinity of hemoglobin for oxygen.
AB  - We studied the effect of correction of the L-arginine-NO system on the fever
      reaction and prooxidant-antioxidant state in rats with increased hemoglobin
      oxygen affinity caused by sodium cyanate after intramuscular injection of
      lipopolysaccharide. The imbalance between parameters of the prooxidant
      antioxidant state in rats with increased hemoglobin oxygen affinity was least
      pronounced after lipopolysaccharide administration. Correction of the L-arginine
      NO system in rats with increased hemoglobin oxygen affinity had no effect on the
      contents of Schiff bases and antioxidants after lipopolysaccharide
      administration.

PMID- 11329077
TI  - Role of the central nervous system in hemopoiesis regulation during experimental
      neuroses.
AB  - Pharmacological blockade of dopamine- and serotoninergic structures with
      haloperidol and cyproheptadine, respectively, attenuated hyperplasia of bone
      marrow granulocytopoiesis and erythropoiesis (cyproheptadine) caused by conflict
      situation. At the same time, haloperidol and, especially, cyproheptadine
      normalized suppressed erythropoiesis and modulated activated granulocytopoiesis
      under conditions of paradoxical sleep deprivation. These results indicate that
      central regulation of hemopoietic stems is mediated by different neurotransmitter
      mechanisms. Erythropoiesis depends on the state of serotoninergic structures,
      while granulocytopoiesis is regulated both by the dopamine- and serotoninergic
      systems.

PMID- 11329078
TI  - The role of neurochemical mechanisms of ventromedial hypothalamus in various
      models of anxiety in rats.
AB  - Microinjections of glutamic acid, serotonin, and sulpiride in the ventromedial
      hypothalamus reduced anxiety in an illuminated platform avoidance task in rats,
      while dopamine, apomorphine, picrotoxin, and memantine increased it. Similar
      injections of phenylephrine and yohimbine reduced anxiety in threatening
      situation task only, while GABA reduced it in both tasks. It is suggested that
      various emotional and stress phenotypes are realized through functionally
      different neurochemical mechanisms of ventromedial hypothalamus.

PMID- 11329079
TI  - Role of mononuclear phagocyte system in hemopoiesis regulation in AKR/JY mice
      during preleukemic period.
AB  - Feeder activity of bone marrow adherent cells and peritoneal macrophages is
      decreased and colony-stimulating and erythropoietic activity of unfractionated
      bone marrow increased in highly leukemic AKR/JY mice in comparison with CBA/CaLac
      mice. At the same time maturation of hemopoietic precursor cells in AKR/JY mice
      is delayed compared to controls. This indicates compensatory activation of
      nonadherent elements of the hemopoiesis-inducing microenvironment against the
      background of suppressed activity of adherent elements. Hence, leukemogenic virus
      produced a systemic damage to target cells (e.g. mononuclear phagocyte system),
      which probably represent a mechanism of leukemic transformation in AKR/JY mice.

PMID- 11329080
TI  - Formation of morphine tolerance in offspring of morphine-tolerant animals:
      neurochemical and neuroimmune correlates.
AB  - We carried out a complex physiological, neurochemical, and neuroimmunologic study
      of the formation of tolerance to analgetic effect of morphine and analyzed
      enkephalinase A activity in different brain structures and serotonin antibodies
      in the serum. More early development of morphine tolerance and a sharp increase
      in serum antibody titer was found in the offspring of morphine-tolerant rats.
      This points to an imbalance in the neurotransmitter system and can serve as a
      diagnostic marker of endogenous opioid system pathology.

PMID- 11329081
TI  - Role of nitric oxide and lipid peroxidation in mechanisms of febrile convulsions
      in Wistar rat pups.
AB  - Generation of nitric oxide and the content of lipid peroxidation products in the
      brain are increased in rat pups during febrile convulsions. NO-synthase inhibitor
      N-nitro-L-arginine in a dose of 250 mg/kg prevented hyperthermia-induced
      accumulation of nitric oxide, increased the latency febrile convulsions, and had
      no effect on the content of lipid peroxidation products.

PMID- 11329082
TI  - Role of apolipoprotein A-I in steroid-induced activation of DNA and protein
      synthesis in hepatocytes.
AB  - It is demonstrated that anabolic effect of steroid hormones is produced by
      steroid-apolipoprotein A-I complexes. These complexes accelerate not only
      protein, but also DNA synthesis and produce both cell hypertrophy and
      hyperplasia. For realization of their anabolic effect steroid hormones are
      modified by alpha- and beta-reductases in resident macrophages.

PMID- 11329083
TI  - Effects of electroactivated solutions on antioxidant enzymes.
AB  - Electrochemically activated systems normalized activity of antioxidant enzymes
      catalase, peroxidase, and superoxide dismutase. The baseline activity of
      antioxidant enzymes considerably varies in humans and animals. This effect of
      electrochemically activated systems having negative oxidation-reduction potential
      was probably related to a training effect of excess electrons.

PMID- 11329084
TI  - Effect of acute alcohol administration on cerebral tyrosine hydroxylase mRNA
      level in mice with different ethanol sensitivity.
AB  - The levels of tyrosine hydroxylase mRNA in different brain regions of inbred mice
      with different sensitivity to alcohol were evaluated. This parameter was also
      measured 2, 4, and 6 h after single intraperitoneal injection of ethanol. We
      revealed interstrain differences in expression of tyrosine hydroxylase gene in
      the cerebral cortex, hypothalamus, and locus ceruleus. Single ethanol injection
      caused different changes in tyrosine hydroxylase gene expression and reduced the
      interstrain differences. We conclude that the system of long-term regulation of
      tyrosine hydroxylase gene is involved in the mechanisms of congenital alcohol
      sensitivity.

PMID- 11329085
TI  - Antipyretic effect of neuropeptide galanin in endotoxin-induced fever.
AB  - Neuropeptide galanin produces a antipyretic effect in experimental pyrogenic
      reaction induced by intraperitoneal injection of lipopolysaccharide. Central
      intracerebroventricular injection of 100 ng galanin significantly attenuated, but
      did not completely abolish fever. Central galanin injection potentiated endotoxin
      induced activation of the noradrenergic system and blocked activation of the
      serotoninergic system of the anterior hypothalamus.

PMID- 11329086
TI  - Asymmetry in cerebral hemispheres and thymus lobes during realization of humoral
      immune response in mice.
AB  - We studied the role of functional asymmetry in mouse brain and thymus in the
      realization of humoral immune response. We concluded that not only nervous system
      asymmetry, but also immune system asymmetry and the relationship between cerebral
      hemispheres and cells of the right and left thymus lobes play an important role
      in the regulation of immune response.

PMID- 11329087
TI  - Urokinase and tissue plasminogen activators and their inhibitor PAI-1 in human
      tumors.
AB  - The content of urokinase and tissue plasminogen activators and their inhibitor
      PAI-1 in tumors and histologically intact tissues from patients with breast,
      ovarian, and non-small-cell lung cancer was measured by enzyme immunoassay. The
      content of urokinase plasminogen activator and PAI-1 considerably increased in
      all malignant tumors, however the correlation between the expression of
      components of the plasminogen activation system and clinical morphological
      feature and prognosis of the disease depends on the type of tumor.

PMID- 11329088
TI  - Molecular mechanisms of different sensitivity of tumor cells to dexamethasone.
AB  - The response of two cell lines, CSML-0 (does not express metastasin) and CSML-100
      (high expression of metastasin) to cytolytic action of glucocorticoid was
      studied. Dexamethasone (1 microM) induced apoptosis of CSML-0 cells, while CSLM
      100 cells were resistant to its cytolytic action. Apoptotic death of CSLM-100
      cells was induced by incubation with dexamethasone in the presence of Ca-ATPase
      inhibitors, vanadate or thapsigargin. Metastasin, a proteins of the S-100 family,
      activated Ca-ATPase and ATP-dependent Ca2+ transport in plasmolemmal fraction of
      CSML-100 cells. Experiments showed that metastasin-induced activation of Ca
      ATPase is a possible mechanisms of CSML-100 cell resistance to cytolytic
      dexamethasone action.

PMID- 11329089
TI  - Heart rhythm disturbances during the acute period of massive pulmonary embolism.
AB  - We studied the type, incidence, and dynamics of arrhythmia during the acute phase
      of massive pulmonary embolism complicated or uncomplicated by cardiac
      insufficiency. Complicated and uncomplicated massive pulmonary embolisms were
      accompanied by the appearance of individual and allorhythmic ventricular
      extrasystoles, respectively. The rise of right ventricular pressure to 70 mm Hg
      was critical for the development of allorhythmia. Allorhythmia started 3-268 sec
      after attaining critical ventricular pressure. Heart rhythm spontaneously
      recovered in 100 and 78% animals with uncomplicated and complicated massive
      pulmonary embolism, respectively. The duration of paroxysmal allorhythmia varied
      from 15 sec to 15 min. Electrophysiological processes in the myocardium were
      normalized with progression of uncomplicated massive pulmonary embolism: the
      incidence of single and, in particular, allorhythmic extrasystoles decreased, and
      electrocardiographic parameters returned to normal.

PMID- 11329090
TI  - Reparative effect of epithalon on pineal gland ultrastructure in gamma-irradiated
      rats.
AB  - Electron microscopy of the pineal gland in gamma-irradiated rats treated with
      epithalon revealed ultrastructural signs attesting to enhancement of its
      functional activity.

PMID- 11329091
TI  - Apoptosis in cells of rat sympathetic ganglia during early ontogeny: electron
      microscopic study.
AB  - Postnatal ontogeny of sympathetic ganglia includes both proliferative processes
      and programmed cell death. Electron microscopy helps to evaluate the intensity
      and the relationship between these processes.

PMID- 11329092
TI  - Morphological changes in burn wounds after transplantation of allogenic
      fibroblasts.
AB  - Cultured allogenic fibroblasts labeled with fluorescent acridine orange and
      transplanted onto burn wound virtually completely disappear from the wound
      surface within 2 days (are destroyed). Study of wound morphology by light
      autoradiography and quantitative analysis showed a stimulating effect of
      transplanted fibroblasts on wound healing. This effect, irrespective of the
      initial state of the wound, is always directed at accelerated formation of
      connective tissue similar to the derma and capable of epithelialization.

PMID- 11329093
TI  - Detection of rifampicin-resistant Mycobacterium tuberculosis strains by
      hybridization and polymerase chain reaction on a specialized TB-microchip.
AB  - Two alternative methods for identification of rifampicin-resistant strains of
      Mycobacterium tuberculosis on biological microchips are developed. The methods
      are based on detection of point mutations and other rearrangements in the rpoB
      gene region determining rifampicin resistance. Hybridization on TB-microchip
      detects 30 mutant variants of DNA in rifampicin-resistant strains (about 95% of
      all resistant forms). Allele-specific microchip PCR shortens the duration of
      analysis to 1.5 h. These methods can be used in clinical diagnostic laboratories
      for evaluating drug resistance/sensitivity of tuberculosis agent and for
      monitoring of the efficiency of antibiotic therapy.

PMID- 11329094
TI  - Biomarkers and surrogate endpoints.

PMID- 11329095
TI  - The hemodynamic effects of long-term ACE inhibition with fosinopril in patients
      with heart failure. Fosinopril Hemodynamics Study Group.
AB  - The objective of this study was to evaluate the hemodynamic and clinical effects
      of fosinopril in patients with heart failure. This was a prospective,
      multicenter, double-blind, randomized, parallel-group study. Patients 18 to 80
      years of age who were receiving diuretics with a systolic blood pressure (SBP) >
      or = 90 mm Hg, New York Heart Association (NYHA) functional class II-IV, left
      ventricular ejection fraction < or = 40%, pulmonary capillary wedge pressure
      (PCWP) > or = 18 mm Hg, and a cardiac index (CI) < or = 2.6 L/min/m(2) were
      eligible. A total of 179 patients were randomized to a single, double-blind oral
      dose of placebo or fosinopril at 1, 20, or 40 mg, and hemodynamic monitoring was
      performed for 24 hours postdose; 155 patients with SBP > or = 90 mm Hg were re
      randomized to 10 weeks of double-blind fosinopril at 1, 20, or 40 mg once daily.
      Hemodynamic monitoring was repeated at the last visit, beginning at 24 hours
      postdose (trough) and continuing for 12 hours thereafter. Significant decreases
      in preload (PCWP) and afterload (mean arterial blood pressure [MABP] and systemic
      vascular resistance [SVR]) were evident 3 to 4 hours after a single dose of
      fosinopril at 20 and 40 mg and continuing for up to 8 to 12 hours postdose for
      PCWP and SVR and for up to 24 hours postdose for MABP (P < or = .05 v placebo and
      baseline). Sustained decreases in PCWP, MABP, SVR, and heart rate and increases
      in CI and stroke volume index were observed after 10 weeks of treatment with
      fosinopril at 20 and 40 mg once daily (P < or = .05 v 1 mg group for PCWP and
      MABP at most time points and P < or = .05 v baseline for other parameters at most
      time points). Dose-related trends toward reduced supplemental diuretic use (P =
      .027) and reduced symptoms of dyspnea (P = .008) were observed with the 20-mg and
      40-mg fosinopril dose groups. Once daily administration of fosinopril at 20 and
      40 mg was safe and well tolerated, provided a sustained beneficial hemodynamic
      effect, improved left ventricular performance, and reduced symptoms of dyspnea,
      resulting in a reduced need for supplemental diuretic therapy.

PMID- 11329096
TI  - Comparative efficacy and safety of nimesulide versus piroxicam in osteoarthritis
      with special reference to chondroprotection.
AB  - The efficacy and tolerability profile of nimesulide was assessed in a double
      blind, piroxicam-controlled trial in 49 patients with osteoarthritis of the knee
      joint. Nimesulide was administered orally as 100 mg twice daily, and piroxicam
      was administered as 20 mg orally in the morning and placebo in the evening. These
      patients were stratified into two groups: clinical assessment and magnetic
      resonance imaging evaluation of the knee. All patients were followed for 8 weeks
      with clinical assessment every 2 weeks; of these, 11 patients were selected for
      magnetic resonance imaging evaluation, and they were treated for 24 weeks. The
      principal efficacy parameters were improvement in osteoarthritis severity index,
      joint tenderness, swelling, and functional capacity of the patients. The final
      judgment of efficacy was made by the physician. Nimesulide improved all primary
      and secondary efficacy parameters with an activity comparable to piroxicam.
      Significant reduction in joint swelling and tenderness was observed as early as 2
      weeks in the two treatment groups; however, a greater number of patients were
      relieved in nimesulide group. At 8 and 24 weeks, the number of patients with no
      joint swelling were 66.7% versus 50% and 80% versus 66.7% in the nimesulide and
      piroxicam groups (P <.05). Functional capacity at 8 weeks improved in 72.2% of
      nimesulide and 44.4% of piroxicam recipients. Mild adverse effects, mainly
      gastrointestinal, considered possibly related to treatment were recorded in 4
      patients treated with nimesulide and in 12 patients treated with piroxicam. No
      significant change in the articulating cartilage of the tibiofemoral joint was
      observed over a 24-week period with either treatment. Nimesulide was as
      efficacious as piroxicam in reducing the inflammatory indices, and both drugs
      were equally well tolerated.

PMID- 11329097
TI  - In vitro adsorption of ciprofloxacin on activated charcoal and Talc.
AB  - The in vitro adsorption of ciprofloxacin, a broad-spectrum antimicrobial with
      actions against a wide variety of microorganisms on activated charcoal (AC) and
      talc (TC), was investigated at various pH values that simulate the pH of most
      regions of the gastrointestinal tract. The results of the study indicate that AC
      and TC adsorbed ciprofloxacin effectively. Adsorption depended on the quantity of
      the adsorbents used, and for AC adsorption was complete within 2 hours and for TC
      it was complete within 1 hour with 0.5 g of either of the adsorbents. AC
      exhibited higher adsorptive capacity for ciprofloxacin than TC. Overall, AC and
      TC could be used as effective antidotes in poisoning resulting from
      ciprofloxacin.

PMID- 11329098
TI  - Impact of guidelines to alter antitetanus prophylaxis practices and reduce costs
      in the emergency department.
AB  - The objective of this study was to assess the impact of an intervention to modify
      antitetanus prophylaxis of open wounds. This prospective, before-and-after study
      was conducted in an emergency department of a large metropolitan hospital.
      Consecutive patients with open wounds were managed according to the World Health
      Organization (WHO) guidelines before an intervention, then according to new
      guidelines afterwards. Locally developed guidelines were introduced and backed up
      by a teaching program, with emphasis on reducing unwarranted human tetanus
      immunoglobulins and costs. Serum tetanus antitoxins level was measured in
      postintervention patients mainly to verify the soundness of the intervention,
      eventually to complete patients' protection during follow-up, and to derive more
      reliable recommendations for the future. Main outcome measures included the
      number of treatments conforming to each set of guidelines, the rate of tetanus
      immunoglobulin prescriptions, and the cost of each strategy. Two groups of 389
      and 459 patients were included. Treatment conforming to guidelines increased from
      60% to 79%, undertreatment decreased from 31% to 19%, and overtreatment decreased
      from 9% to 2% (P < 0.001). Tetanus immunoglobulin prescriptions decreased from
      23% to 1% (P < 0.001). On the basis of antitoxins level, 60% of 367
      postintervention patients were correctly treated, 29% were overtreated, and 11%
      were undertreated. Nevertheless, with the WHO guidelines, only 49% would have
      been correctly treated, 39% would have been overtreated (29% with
      immunoglobulins), and 12% would have been undertreated (P < 0.001). Costs
      decreased from $32 to $24 per patient. New guidelines resulted in improved
      tetanus prophylaxis at reduced costs in an emergency department. Because they
      rely on immunization history, however, guidelines currently in use are
      misleading. More reliable recommendations, including a test for tetanus antibody
      status in some cases, are needed.

PMID- 11329099
TI  - Steady-state pharmacokinetics of high-dose diltiazem hydrochloride (Cardizem CD)
      administered once daily in healthy volunteers.
AB  - The once-daily formulation of diltiazem hydrochloride (Cardizem CD) is marketed
      for the treatment of essential hypertension and stable angina pectoris. The
      steady-state pharmacokinetics of once-daily diltiazem and its metabolites,
      desacetyldiltiazem (DAD) and N-desmethyldiltiazem (MA), were examined in two
      groups of eight healthy subjects each. The first group (group A) received 240,
      480, and 720 mg diltiazem once daily for 7 days in a single-blind, stair-step,
      dose-escalation design. The second group (group B) received 180, 360, and 720 mg
      diltiazem in a similar manner. At each dose level, serial blood samples were
      collected for up to 24 hours after the last (seventh) dose. Plasma samples were
      analyzed for diltiazem and the metabolites by high-performance liquid
      chromatography. The disposition of diltiazem, DAD, and MA was nonlinear over the
      240- to 720-mg (group A) and 180- to 720-mg (group B) diltiazem dose ranges
      studied. In group A, mean diltiazem area under the plasma concentration-time
      curve (AUC) at the 240-mg dose level was 2410 h.ng/mL compared with 10,167
      h.ng/mL at the 720-mg dose level. In group B, mean diltiazem AUC at the 180-mg
      dose level was 1092 h.ng/mL compared with 8398 h.ng/mL at the 720-mg dose level.
      The apparent oral clearance decreased 35% over a threefold dose range (group A)
      and 51% over a fourfold dose range (group B). Mean ratios of AUCDAD/AUC(DILT)
      were similar at all dose levels. Mean AUCMA/AUC(DILT) ratios, however, decreased
      with increasing diltiazem dose, suggesting that the nonlinear disposition of MA
      may be less pronounced than that of parent drug.

PMID- 11329100
TI  - Comparison of 7 versus 10 days of antibiotic therapy for hospitalized patients
      with uncomplicated community-acquired pneumonia: a prospective, randomized,
      double-blind study.
AB  - The objective of this study was to compare the outcome of 7 versus 10 days of
      antibiotic therapy for inpatients with moderately severe community-acquired
      pneumonia (CAP). A prospective, randomized, double-blind study with a follow-up
      period of 42 days was conducted. Fifty-two veterans were treated with 2 days of
      cefuroxime at 750 mg intravenously every 8 hours followed by group 1, 8 days oral
      therapy, and group 2, 5 days oral therapy followed by 3 days of placebo. Oral
      therapy consisted of cefuroxime axetil at 500 mg every 12 hours. No difference
      was seen in cure rates: 20 of 22 (90.9%) patients in group 1 and 21 of 24 (87.5%)
      patients in group 2. There were no late recurrences. Potential US cost-savings is
      $27.2 million. Inpatients with moderately severe CAP can be treated with 2 days
      of intravenous antibiotics followed by 5 additional days of oral antibiotics.
      Longer treatment duration prolongs the cost of care, without increasing the cure
      rate or decreasing the pneumonia recurrence rate.

PMID- 11329101
TI  - Amiodarone in the treatment of junctional ectopic tachycardia after cardiac
      surgery in children: report of two cases and review of the literature.
AB  - Junctional ectopic tachycardia (JET) occurs most frequently after operative
      repair of congenital heart defects. The mechanism is thought to involve direct
      trauma to the atrioventricular node and His bundle resulting in an ectopic focus.
      Several therapeutic methods have been described in the pediatric literature with
      varying degrees of success and complication rates. Because heart rates may exceed
      200 to 300 beats per minute, there may be inadequate time for ventricular
      filling. Ventricular filling can be further compromised because of the asynchrony
      between the atria and the ventricles. These factors can lead to significant
      compromise of cardiovascular function in the postoperative patient. We describe
      our experience with amiodarone in two patients who developed postoperative JET
      after repair of congenital heart defects. Dosing regimens and previous experience
      with amiodarone in patients with JET are reviewed.

PMID- 11329102
TI  - T-channel-selective calcium channel blockade: a promising therapeutic
      possibility, only preliminarily tested so far: a review of published data. T
      Channel Calcium Channel Blocker Study Group.
AB  - Basic studies as well as short-term clinical trials of the T-channel-selective
      calcium channel blocker, mibefradil, are reviewed. The compound reduced afterload
      and was effective for the symptomatic treatment of hypertension and stable angina
      pectoris. It did not display any relevant negative inotropic or positive
      chronotropic effect. Mibefradil has been withdrawn by the manufacturer because of
      drug interaction at the cytochrome P-450 3A4 enzyme. It is hoped that new T
      channel-selective calcium channel blockers will be developed to explore further
      this promising but so far only preliminarily tested therapeutic possibility.

PMID- 11329103
TI  - Reorganizing the flow of scientific information: is the age of electronic
      journalism here?

PMID- 11329104
TI  - Transesophageal pacemaker therapy in atrial flutter after procainamide
      pretreatment.
AB  - Transesophageal atrial stimulation was applied in 56 patients to terminate atrial
      flutter. Extrastimulation and atrial burst techniques were applied using
      programmable stimulator (Medtronic 5328) and hexapolar esophageal electrode
      catheters. Thirty patients were randomized to receive digoxin pretreatment (group
      A), and 26 patients were randomized to receive procainamide pretreatment (group
      B). Efficacy of each pretreatment was evaluated by observing the change in the
      rhythm. In group A, transesophageal pacemaker therapy successfully converted
      atrial flutter to sinus rhythm in 13 patients and to atrial fibrillation in 14
      patients, whereas the arrhythmia remained unchanged in the 3 remaining patients
      in the digitalized group. In group B, after procainamide pretreatment, sinus
      rhythm appeared in 19 and atrial fibrillation in 5, and no change was observed in
      the remaining 2 patients. Procainamide is more efficacious than digoxin (P <
      0.05) in facilitating cardioversion by transesophageal stimulation.

PMID- 11329105
TI  - Carboxyhemoglobin and lactate levels do not correlate in critically ill patients.
AB  - Endogenous carbon monoxide (CO) is produced in the degradation of heme by heme
      oxygenase. Studies have shown that hypoxia induces heme oxygenase production of
      CO in vascular tissue. Because elevated plasma lactate levels are associated with
      tissue hypoxia, we determined if there was any correlation between lactate and
      carboxyhemoglobin (COHb) levels in a group of critically ill patients with a high
      likelihood of hypoxia. In a 7.5-month period, 5322 simultaneous arterial COHb and
      lactate measurements were performed routinely on 183 patients with a blood gas
      analyzer in the Department of Veterans Affairs Medical Center, Bronx, New York,
      Surgical Intensive Care Unit. Sixty-one percent of the patients had elevated
      lactate levels (> 2.5mmol/L), and 46% had elevated COHb levels (> 1.5%). Lactate
      levels ranged from 0.12 to 22.7 mmol/L and COHb levels from 0% to 4.8%. There was
      no correlation between lactate and COHb levels (r = .07 with P < .0001). Levels
      of endogenous CO do not increase in situations in which lactate production is
      increased. It is possible that changes in endogenous production of CO may not
      significantly affect the circulating level of COHb. Although readily available,
      COHb levels do not seem to be clinically useful as markers of critical illness.

PMID- 11329106
TI  - Medical application of engineering risk analysis and anesthesia patient risk
      illustration.
AB  - The engineering risk analysis method can be extended to include some human and
      organizational factors and can be used in the medical domain; this transfer is
      illustrated by a description of a study of anesthesia patient risk. This study
      involves first a dynamic analysis of accident risks. The model is then extended
      by relating the basic events of accident scenarios to the state of the
      practitioner described by the probability of personal problems that may affect
      his or her level of competence and alertness. These potential problems, in turn,
      are linked (by probabilistic relations) to the way the system is managed. This
      extension of the analytical framework allows assessment of the effect of
      particular types of practitioner problems and therefore of corresponding risk
      mitigation measures on the probability of the different accident scenarios. The
      risk analysis model can then be used as a management tool that permits setting
      priorities among patient safety measures, based either on the sole benefits of
      the corresponding decrease of patient risk or on a cost-to-benefit ratio. This
      probabilistic approach constitutes a departure from the classic risk studies
      exclusively based on statistical frequencies because it involves both available
      statistics and expert opinions. It is commonly used in engineering for systems
      for which there is not enough information at the time when decisions need to be
      made. I show here how the probabilistic model can be used in the medical field to
      support patient safety decisions before complete data sets can be gathered or in
      cases in which some key factors are not directly observable.

PMID- 11329107
TI  - Effect of angiotensin-converting enzyme therapy on QT interval dispersion.
AB  - Patients with chronic heart failure (CHF) have an increased risk for sudden
      death. This increased risk has been associated with increased QT dispersion
      (QTd), a reflection of the heterogeneity in ventricular repolarization.
      Angiotensin-converting enzyme (ACE) inhibitors have been reported to decrease
      heart size as well as decreasing morbidity and mortality in moderate-to-severe
      CHF. The aim of this study was to determine if ACE therapy is associated with a
      decrease in QTd, a marker for increased electrical instability. Ninety-seven
      patients were evaluated. The normalized QTd after 2 months of ACE therapy
      decreased from 16 +/- 4 to 12 +/- 3, a 25% reduction in dispersions. QTd also
      decreased from 61 +/- 14 to 47 +/- 12 (P < .001) and QTc dispersions decreased
      from 71 +/- 18 to 52 +/- 14 (P < .001). After 2 months of ACE inhibitor therapy,
      heart rate slowed significantly (RR intervals 765 +/- 198 before and 838 +/- 186
      after ACE). There was a negative correlation between ejection fraction and QTd (r
      = -0.8; P < .001). The study also found no correlation between ACE level, percent
      converting enzyme inhibition, and QTd. The effects of ACE therapy appear early on
      in terms of repolarization changes. The reduction in QTd may explain the reduced
      sudden death mortality in patients with heart failure who are treated with ACE
      inhibitor therapy.

PMID- 11329108
TI  - Pediatric research: coming of age in the new millennium.
AB  - One of the many provisions of the recently enacted Food and Drug Administration
      Modernization Act (FDAMA) provides for an additional period of market exclusivity
      in exchange for completed pediatric studies requested by the FDA for certain
      drugs of potential benefit to the pediatric population. The impetus for this law
      centers around two facts: Drugs needed in the pediatric population lack labeling
      for pediatric use, and industry lacks incentive to perform studies to support
      this additional labeling. Congress has now provided the incentive. The success of
      the pediatric initiative will rest initially on industry's willingness and
      readiness to do the studies. This willingness, in turn, will depend on FDAMA's
      impact on the economics of drug development and the availability of pediatric
      research capacity, both of which could be affected by the FDA's final rule on the
      assessment of safety and effectiveness of drugs and biologicals for pediatric
      patients. This rule will compel firms to conduct pediatric studies similar to the
      ones encouraged under FDAMA's voluntary pediatric exclusivity program. Although
      the Act provides for the statutory harmonization of the rule with the Act,
      whether the effects of the rule on the Act have been fully contemplated is a
      premise considered in this article. Congress too has much to contemplate as they
      evaluate the FDA's report, due in less than 2 years, on the public health
      effectiveness and economic effects of the Act's incentive program in preparation
      for possible FDAMA II modifications.

PMID- 11329109
TI  - Initial experience with fenoldopam in children.
AB  - Fenoldopam is a direct-acting vasodilator that acts at the postsynaptic dopamine
      1 receptors in renal, coronary, cerebral, and splanchnic vasculature resulting in
      arterial dilation and a lowering of the mean arterial pressure (MAP). Preliminary
      evidence suggests its efficacy in the treatment of hypertensive urgencies and
      emergencies in adults. We present four children in whom fenoldopam was used to
      control MAP in various clinical scenarios, including hypertensive emergencies and
      urgencies, intraoperative reduction of MAP for controlled hypotension, and
      control of MAP during extracorporeal membrane oxygenation. The possible
      applications of fenoldopam and suggested dosing regimens in children are
      reviewed.

PMID- 11329110
TI  - International symposium on drug development.

PMID- 11329111
TI  - Medical judgment and therapeutics.

PMID- 11329112
TI  - Outcome evaluation of long-term nasal continuous positive airway pressure therapy
      in obstructive sleep apnea.
AB  - A study was conducted at the Tri-State Sleep Disorders Center of Cincinnati,
      Ohio, to evaluate both quantitative and qualitative daily function and
      productivity outcomes of treating obstructive sleep apnea (OSA) with nasal
      continuous positive airway pressure (NCPAP). This was a prospective outcome study
      conducted in 316 patients with diagnosed and treated OSA. There were 234 men and
      82 women, mean age, 48.79 +/- 0.67 years; weight averaged 250.39 +/- 3.55 pounds;
      mean pretreatment respiratory disturbance index was 42.9 +/- 1.7 episodes per
      hour and 2.8 +/- 0.2 episodes per hour with NCPAP treatment. Patients were
      surveyed by questionnaire, administered on polysomnographic confirmation of OSA
      and after 6 months of nightly treatment with NCPAP as to their perceptions of
      their level of daytime functioning and quality of life over the previous 6
      months. Main outcome measures included number of incidents of excessive daytime
      sleepiness; number of headaches on awakening; number of automobile accidents and
      near-miss automobile accidents; number of days absent from work; number of
      physician visits; and a series of subjective scales, measuring job productivity,
      quality of life, general physical and mental condition, short-term memory, and
      changes in blood pressure. Significant decreases were found in the number of
      incidents of excessive daytime sleepiness, headaches on awakening, physician
      visits, days absent from work, and automobile accidents or near misses with NCPAP
      therapy. Patients also reported subjective increases in productivity, quality of
      life, physical and mental condition, and short-term memory and reduction in both
      diastolic and systolic blood pressure. Effective treatment of OSA results in
      improvement both in preexisting symptoms and in quality of life. Improvement in
      many of the major problems experienced by patients seeking treatment has
      important implications for preventive medicine as well as health care cost
      containment.

PMID- 11329113
TI  - Lack of hematologic effects of recent ethanol ingestion by trauma patients.
AB  - A retrospective investigation was conducted to determine if acute ethanol (EtOH)
      ingestion before injury leads to hematologic impairment as noted by coagulation
      and transfusion parameters. Patients older than 18 years of age were grouped
      according to the presence or absence of detectable EtOH concentrations in the
      blood, with further subdivision based on an Injury Severity Score of 8 or less or
      9 or more. The following direct and indirect indicators of hematologic function
      were studied: volume of resuscitation fluids administered (including blood
      products), prothrombin time, partial thromboplastin time, and hematocrit. Of the
      304 patients who were evaluated, 152 had detectable EtOH concentrations and 136
      had undetectable EtOH concentrations; 16 patients had not been tested for blood
      EtOH concentrations and were excluded from the analysis. There were no
      significant differences between groups with regard to blood or fluid requirements
      or coagulation parameters. Detectable blood EtOH concentrations in trauma
      patients are not associated with significant changes in transfusion requirements
      or coagulation parameters compared to patients without detectable EtOH
      concentrations.

PMID- 11329114
TI  - The effect of calcium citrate on bone density in the early and mid-postmenopausal
      period: a randomized placebo-controlled study.
AB  - This placebo-controlled randomized trial was conducted to ascertain the value of
      calcium citrate supplementation in averting bone loss in 63 postmenopausal women,
      57 of whom were early postmenopausal (five years after menopause) and six of whom
      were mid-postmenopausal (five to ten years after menopause). Bone density data
      were available for 25 women who took 800 mg of calcium citrate daily and 31 women
      who received placebo for one to two years. The two groups were similar in
      baseline age, years postmenopause (3.3 in the calcium citrate group vs 2.7 in the
      placebo group), height, weight, calcium intake, and L2-L4 bone density. L2-L4
      bone density did not change during calcium citrate treatment (+ 1.03% after two
      years), whereas it declined significantly by -2.38% after two years on placebo (P
      < .001). Femoral neck bone density did not change in either group. Radial shaft
      bone density did not change in the calcium citrate group (-0.02% after two
      years), but it declined significantly in the placebo group (-1.79% after one year
      and -3.03% after two years, P < .01). The difference in bone density of the L2-L4
      vertebrae and radial shaft after two years of treatment was significant between
      the two groups. An analysis of covariance disclosed no significant effect of
      calcium citrate on L2-L4 bone density during the first three years after
      menopause, but a protective effect after three years. Although serum PTH did not
      change, serum and urinary calcium increased and serum calcitriol and urinary
      phosphorus decreased in the calcium citrate group, indicative of parathyroid
      suppression. Serum bone-specific alkaline phosphatase and osteocalcin, and
      urinary hydroxyproline and N-telopeptide decreased during some calcium citrate
      treatment periods, indicative of a reduction in bone turnover. Thus, calcium
      citrate supplementation (400 mg of calcium twice daily) averted bone loss and
      stabilized bone density in the spine, femoral neck, and radial shaft in women
      relatively soon after menopause. This bone-sparing action was probably due to the
      inhibition of bone resorption from parathyroid suppression.

PMID- 11329115
TI  - Meta-analysis of calcium bioavailability: a comparison of calcium citrate with
      calcium carbonate.
AB  - OBJECTIVE: To perform a meta-analysis of data from available published trials
      comparing the bioavailability of calcium carbonate with that of calcium citrate.
      DATA SOURCES: The whole set was comprised of 15 studies involving 184 subjects
      who underwent measurement of calcium absorption from calcium carbonate and
      calcium citrate. Category A excluded four studies for lack of physiological
      relevance, use of a mixed preparation with low content of calcium carbonate, or
      wide variability in results. Category B was comprised of five studies (from
      Category A) involving 71 subjects who took calcium supplements on an empty
      stomach. Category C was comprised of six studies (from Category A) involving 65
      subjects who took calcium preparations with meals. METHOD: The meta-analysis of
      calcium absorption data from calcium carbonate and calcium citrate, with
      calculation of effect size and 95% confidence intervals. RESULTS: Calcium
      absorption from calcium citrate was consistently significantly higher than that
      from calcium carbonate by 20.0% in the whole set, by 24.0% in Category A, by
      27.2% on an empty stomach, and by 21.6% with meals. CONCLUSION: Calcium citrate
      is better absorbed than calcium carbonate by approximately 22% to 27%, either on
      an empty stomach or co-administered with meals.

PMID- 11329116
TI  - Calcium bioavailability.

PMID- 11329117
TI  - The importance of calcium in postmenopausal women.

PMID- 11329118
TI  - Therapeutic uses of gallium nitrate: past, present, and future.
AB  - Injectable gallium (Ga) nitrate, approved in the United States for the treatment
      of hypercalcemia of malignancy, has been known for more than 2 decades to have
      immunosuppressive properties. At therapeutic doses, it has few adverse effects,
      although high-dose infusions may result in severe nephrotoxicity, particularly in
      patients who are not adequately hydrated, and severe anemia. In animal models, Ga
      has been shown to have efficacy in the treatment of adjuvant arthritis, type 1
      diabetes, experimental autoimmune encephalomyelitis, experimental pulmonary
      inflammation, cardiac allograft rejection, experimental autoimmune uveitis,
      endotoxic shock, and systemic lupus erythematosus. Clinical trials have
      demonstrated efficacy in Paget's disease of bone and activity against some
      malignancies, including epithelial ovarian carcinoma, non-squamous cell carcinoma
      of the cervix, bladder cancer, and non-Hodgkin's lymphoma. Other clinical trials
      underway include studies of sarcoidosis and rheumatoid arthritis. Future studies
      should be conducted not only in other autoimmune diseases, such as multiple
      sclerosis, but also in graft-versus-host disease, leprosy, and acquired
      immunodeficiency syndrome (AIDS).

PMID- 11329119
TI  - University of Miami division of clinical pharmacology therapeutic rounds: issues
      in prescribing for geriatric patients and emerging practice guidelines.
AB  - The geriatric population accounts for over 12% of the United States population
      and consumes over 25% of all prescription medications. Polypharmacy and patient
      noncompliance are often encountered in caring for these patients. These issues
      along with a variety of age-related physiologic changes and the presence of
      multiple medical illnesses place the elderly at an increased risk for adverse
      drug reactions. Especially worrisome is the use of long-acting benzodiazepines
      and anticholinergic medications in this population. The problem of adverse drug
      reactions is a common clinical problem that is of great public concern as the
      number of older persons in the United States continues to grow. In response, a
      variety of proactive measures have been developed. These measures include the
      development of consensus criteria for inappropriate medications, federal
      government regulation, expansion of the role of clinical pharmacists, and
      computer-assisted prescribing protocols.

PMID- 11329124
TI  - Evaluation of T cell receptor gene rearrangement excision circles after
      antiretroviral therapy in children infected with human immunodeficiency virus.
AB  - Immune reconstitution after antiretroviral therapy in human immunodeficiency
      virus (HIV)infected patients may result from the recovery of thymus function,
      peripheral redistribution, or decreased T cell destruction. This study
      investigated levels of T cell receptor gene rearrangement excision circles
      (TRECs) as a measure of recent thymic emigrant cells in peripheral blood
      lymphocytes of 50 HIV-infected infants and children who were followed-up for 40
      months after the start or change of antiretroviral therapy. At baseline, patients
      exhibited fewer TRECs than did uninfected control subjects. The increase in TRECs
      after antiretroviral therapy was greater in infants than in older HIV-infected
      children. Of interest, patients who demonstrated discordant responses (i.e.,
      increased CD4 T cell counts without significant virologic suppression) also had
      substantial gains in TRECs. Furthermore, TRECs correlated positively with the
      number of CD4 and naive T cells and negatively with age and virus load.
      Measurement of TRECs may serve as a useful tool for evaluating immune
      reconstitution in HIV-infected children receiving antiretroviral therapy.

PMID- 11329125
TI  - Radial glia development in the mouse olfactory bulb.
AB  - Radial glia are critical for cell migration and lamination of the cortex. In most
      developing cortical structures, radial glia, as their name suggests, extend
      processes from the ventricle to the pia in regular parallel arrangements.
      However, immunohistochemical labeling from several laboratories suggests that
      radial glia have a more branched morphology in the olfactory bulb. To investigate
      the morphology of radial glia in the mouse olfactory bulb we (1) labeled radial
      glia and olfactory receptor neuron axons at 24-hour intervals by
      immunohistochemistry; and (2) developed a novel method of generating and applying
      "nanocrystals" of 1,1'-dioctadecyl-3,3,3',3'- tetramethylindocarbocyanine
      perchlorate (DiI) to the ventricle surface such that the processes of single
      olfactory bulb radial glia are labeled in the embryonic olfactory bulb. We
      examined the structure and interactions of radial glia with ingrowing olfactory
      receptor neuron (ORN) axons in late embryonic olfactory bulb development. These
      results showed that olfactory bulb radial glia do not form straight parallel
      structures as do radial glia in the neocortex but rather have a convoluted
      trajectory from the ventricle to the bulb surface. Moreover, olfactory bulb
      radial glia consistently extend tangential branches at the level of the internal
      plexiform layer. Beginning at embryonic day 17.5, two types of radial glia can be
      distinguished: type I radial glia have a process that extends from the ventricle
      into the glomerular layer. These apical processes form highly restricted tufts,
      or "glial glomeruli" at the same time that ORN axons are forming "axonal
      glomeruli." In type II radial glia the apical process does not enter the
      glomerular layer but instead ramifies within the external plexiform layer. The
      tight spatiotemporal relationship between the glomerulization of radial glia
      processes and ORN axons during development suggest that radial glia processes
      could play a role in the formation and/or stabilization of mammalian glomeruli.

PMID- 11329126
TI  - Nr-CAM expression in the developing mouse nervous system: ventral midline
      structures, specific fiber tracts, and neuropilar regions.
AB  - Nr-CAM is a member of the L1 subfamily of cell adhesion molecules (CAMs) that
      belong to the immunoglobulin superfamily. To explore the role of Nr-CAM in the
      developing nervous system, we prepared specific antibodies against both chick and
      mouse Nr-CAM using recombinant Fc fusion proteins of chick Nr-CAM and mouse Nr
      CAM, respectively. First, we show the specificity of the new anti-chick Nr-CAM
      antibody compared with a previously employed antibody using the expression
      patterns of Nr-CAM in the chick spinal cord and floor plate and on commissural
      axons, where Nr-CAM has been implicated in axon guidance. Using the anti-mouse Nr
      CAM antibody, we then studied the expression patterns of Nr-CAM in the developing
      mouse nervous system along with the patterns of two related CAMs, L1, which
      labels most growing axons, and TAG-1, which binds to Nr-CAM and has a more
      restricted distribution. Major sites that are positive for Nr-CAM are specialized
      glial formations in the ventral midline, including the floor plate in the spinal
      cord, the hindbrain and midbrain, the optic chiasm, and the median eminence in
      the forebrain. Similar to what is seen in the chick spinal cord, Nr-CAM is
      expressed on crossing fibers as they course through these areas. In addition, Nr
      CAM is found in crossing fiber pathways, including the anterior commissure,
      corpus callosum, and posterior commissure, and in nondecussating pathways, such
      as the lateral olfactory tract and the habenulointerpeduncular tract. Nr-CAM, for
      the most part, is colocalized with TAG-1 in all of these systems. Based on in
      vitro studies indicating that the Nr-CAM-axonin-1/TAG-1 interaction is involved
      in peripheral axonal growth and guidance in the spinal cord [Lustig et al. (1999)
      Dev Biol 209:340-351; Fitzli et al. (2000) J Cell Biol 149:951-968], the
      expression patterns described herein implicate a role for this interaction in
      central nervous system axon growth and guidance, especially at points of
      decussation. Nr-CAM also is expressed in cortical regions, such as the olfactory
      bulb. In the hippocampus, however, TAG-1-positive areas are segregated from Nr
      CAM-positive areas, suggesting that, in neuropilar regions, Nr-CAM interacts with
      molecules other than TAG-1.

PMID- 11329127
TI  - CART peptide-immunoreactive projection from the nucleus accumbens targets
      substantia nigra pars reticulata neurons in the rat.
AB  - Cocaine and amphetamine regulated transcript (CART) was originally identified as
      a mRNA which increases in the striatum after acute cocaine or amphetamine
      administration in rats. In addition, intra-ventral tegmental (VTA) area
      injections of CART peptides produce psychostimulant-like behavioral effects. CART
      peptide immunoreactivity (CARTir) has been localized in discrete nuclei
      throughout the brain, and, within the striatum, it is located only ventrally in a
      subpopulation of medium spiny projection neurons in the shell and core of the
      nucleus accumbens. To better understand the potential role of CART peptides in
      the mechanism of action of psychomotor stimulants, we analyzed the distribution
      and synaptic connectivity of CARTir terminals in the ventral midbrain. CARTir
      terminal-like varicosities were located throughout the rostrocaudal extent of the
      substantia nigra (SN), VTA, and retrorubral field (RRF). They were particularly
      abundant in the dorsomedial SN where they overlapped with non-dopaminergic
      substantia nigra pars reticulata (SNr) neurons and proximal dendrites of
      dopaminergic substantia nigra pars compacta (SNc) neurons. CARTir terminals were
      also in register with dopaminergic perikarya in the ventromedial part of the
      rostral SNc. In many instances, CARTir terminals ensheathed dendrites of SNr
      neurons. To characterize the postsynaptic targets and potential sources of CARTir
      terminals in the SN, electron microscopic observations were conducted. Ninety
      percent of the CARTir terminals examined displayed the ultrastructural features
      of boutons of striatal origin and 80% of them formed symmetric synapses with
      distal dendrites of SNr neurons. To further elucidate the source of CARTir
      terminals in the SN, unilateral excitotoxic lesions directed to the core of the
      nucleus accumbens (Acc) were produced; this led to a dramatic, almost complete
      loss of CARTir terminal staining in the ipsilateral SN, whereas the density of
      CARTir terminals was relatively unchanged in the VTA. In conclusion, this study
      demonstrates the presence of CART peptides in a direct pathway from the accumbens
      to the SNr, thus illustrating a unique feature of CART peptides in that they
      delineate a specific anatomical circuit of the basal ganglia.

PMID- 11329128
TI  - Regenerating optic fibers correct large-scale errors by random growth: evidence
      from in vivo imaging.
AB  - Regenerating optic fibers in goldfish make large-scale errors when they invade
      tectum and subsequently correct these to generate a projection with moderate
      retinotopic order by 1 month. The behavior of fibers underlying these extensive
      rearrangements is not well understood. To clarify this, we have imaged optic
      fibers in living adult goldfish at 2-4 weeks of regeneration. A small number of
      neighboring retinal ganglion cells were labeled with microinjections of DiI and
      imaged in the dorsal tectum with a cooled CCD camera on a fluorescence microscope
      for 5 to 8 hours. Nearly all fibers were simple unbranched processes and had
      endings that were highly dynamic showing both growth and retraction. Fibers from
      dorsal retina that normally innervate ventral tectum were frequently observed in
      dorsal tectum. These ectopic fibers oscillated more frequently between growth and
      retraction and retracted more often than ventral optic fibers. Like retinotopic
      fibers, ectopic fibers exhibited net growth but they showed no apparent
      directional preference toward their retinotopic position. In contrast, large
      errors along the anterior-posterior axis corresponding to nasal-temporal retina
      were rare and there was no differential behavior that distinguished these fibers.

PMID- 11329129
TI  - Embryonic development of the nervous system of the temnocephalid flatworm
      Craspedella pedum.
AB  - The nervous system of temnocephalid flatworms consists of the brain and three
      pairs of longitudinal connectives extending into the trunk and tail. The
      connectives are crosslinked by an invariant number of regularly spaced
      commissures. Branches of the connectives innervate the tentacles of the head and
      the sucker organ in the tail. A set of nerve rings encircling the pharynx and
      connected to the brain and connectives constitute the pharyngeal nervous system.
      The nervous system is formed during early embryogenesis when the embryo
      represents a multilayered mesenchymal mass of cells. Gastrulation and the
      formation of separate epithelial germ layers that characterize most other animal
      groups are absent. The brain arises as a bilaterally symmetric condensation of
      postmitotic cells in the deep layers of the anterior region of the embryonic
      mesenchyme. The pattern of axon outgrowth, visualized by labeling with anti
      acetylated tubulin (acTub) antibody, shows marked differences from the pattern
      observed in other flatworm taxa in regard to the number of neurons that express
      the acTub epitope. Acetylated tubulin is only expressed in neurons that form long
      axon tracts. In other flatworm species, such as the typhloplanoid Mesostoma and
      the polyclad Imogine, which were investigated by us with the acTub antibody
      (Hartenstein and Ehlers [2000] Dev. Genes Evol. 210:399-415; Younossi-Hartenstein
      and Hartenstein [2000] Dev. Genes Evol. 210:383-398), only a small number of
      "pioneer neurons" become acTub positive during the embryonic period. By contrast,
      in temnocephalids, most, if not all, neurons express acTub and form long, large
      diameter axons. Initially, the brain commissure, pharyngeal nerve ring, and the
      connectives are laid down. Commissural tracts and tentacle nerves branching off
      the connectives appear later. We speculate that the precocious differentiation of
      the nervous system may be related to the fact that temnocephalids move by muscle
      action, and possess a massive and complex muscular system when they hatch. In
      addition, they have muscular specializations such as the anterior tentacles and
      the posterior sucker that are used as soon as they hatch. By contrast, juveniles
      of Mesostoma and larvae of polyclads move predominantly by ciliary action that
      may not require a complex neural circuitry for coordination.

PMID- 11329130
TI  - Remodeling of motor terminals during metamorphosis of the moth Manduca sexta:
      expression patterns of two distinct isoforms of Manduca fasciclin II.
AB  - During metamorphosis of the moth Manduca sexta, the neuromuscular system of the
      thoracic legs is reorganized dramatically. Larval leg muscles degenerate at the
      end of larval life, and new adult leg muscles develop during the ensuing pupal
      stage. Larval leg motoneurons persist, but undergo substantial remodeling of
      central and peripheral processes. As part of our on-going investigation of
      mechanisms underlying the remodeling of motor terminals, we have used antisera
      generated against Manduca-specific isoforms of the homophilic adhesion molecule
      fasciclin II (MFas II) to label motor terminals during metamorphosis. Antisera
      generated against the glycosyl-phosphatidylinositol (GPI) -linked isoform of MFas
      II (GPI-MFas II) labeled the motor nerves at all stages and seemed to be
      associated with glial cells ensheathing the peripheral nerves. In addition, the
      anti-GPI-MFas II antisera labeled regions associated with synaptic boutons at
      both larval and adult stages. In contrast, antisera generated against a
      transmembrane isoform of MFas II (TM-MFas II) only labeled specific neuronal
      processes at discrete intervals during remodeling. Identified leg motoneurons
      (such as the femoral depressor motoneuron) expressed detectable levels of TM-MFas
      II in their peripheral processes only during phases of motor-terminal retraction
      and initial stages of motor-terminal re-growth. Putative modulatory neurons (such
      as the unpaired median neurons), however, expressed TM-MFas II in their processes
      during larval stages as well as during remodeling. Use of the isoform-specific
      anti-MFas II antisera provided a novel method for visualizing remodeling of motor
      terminals during metamorphosis and helped distinguish different components of the
      motor nerves and neuromuscular junction.

PMID- 11329131
TI  - Comparison of sensory and sympathetic innervation of the dura mater and posterior
      longitudinal ligament in the cervical spine after removal of the stellate
      ganglion.
AB  - Although cervical spinal tissues are rich in sensory and sympathetic fibers,
      which play a significant role in clinical phenomena, there is little information
      available regarding their anatomical characteristics. In this study, we compared
      the innervation of the cervical dura mater and the posterior longitudinal
      ligament (PLL) to that after removal of the stellate ganglion to determine
      whether the anatomical background plays a significant role in clinical
      manifestations. Immunoreactivities for calcitonin gene-related peptide (CGRP) and
      substance P (SP) were used as sensory markers, and immunoreactivity for
      neuropeptide Y (NPY) was used as a sympathetic marker. Sensory fibers in the
      cervical dura mater were distributed within each cervical segment, but those in
      the PLL extended beyond the segmental borders. A dense sensory fiber network
      forming a single layer was seen at the intervertebral disc region in the cervical
      PLL, whereas sympathetic fibers in this region were sparsely distributed.
      Sympathetic fibers were distributed not only around the vascular wall but also in
      the region independent from vessels, and some occasionally ran together with
      sensory fibers in both the dura mater and the PLL. Removal of the stellate
      ganglion had little effect on the distribution of sensory fibers but denervated
      the sympathetic fiber networks in the region independent from vessels of the
      upper ipsilateral cervical PLL. In conclusion, the cervical dura mater and the
      PLL have different sensory and sympathetic innervations. Sympathetic fibers pass
      through the stellate ganglion to project to the region independent from vessels
      in the upper cervical PLL. Clinical symptoms may be attributed to this
      characteristic innervation of the cervical spine.

PMID- 11329132
TI  - Distribution of ionotropic glutamate receptor subunit mRNAs in the rat
      hypothalamus.
AB  - The excitatory amino acid neurotransmitter glutamate participates in the control
      of most (and possibly all) neuroendocrine systems in the hypothalamus. This
      control is exerted by binding to two classes of membrane receptors, the
      ionotropic and metabotropic receptor families, which differ in their structure
      and mechanisms of signal transduction. To gain a better understanding about the
      precise sites of action of glutamate and the subunit compositions of the
      receptors involved in the glutamatergic neurotransmission in the hypothalamus and
      septum, in situ hybridization was used with 35S-labeled cRNA probes for the
      different ionotropic receptor subunits, including glutamate receptor subunits 1-4
      (GluR1-GluR4), kainate-2, GluR5-GluR7, N-methyl-D-aspartate (NMDA) receptor 1
      (NMDAR1), and NMDAR2A-NMDAR2D. The results showed that subunits of alpha-amino-3
      hydroxy-5-methyl-4-isoxazole-propionate-preferring, kainate-preferring, and NMDA
      preferring receptor subunits are distributed widely but heterogeneously and that
      the GluR1, GluR2, kainate-2, NMDAR1, NMDAR2A, and NMDAR2B subunits are the most
      abundant in the hypothalamus. Thus, GluR1 subunit mRNA was prominent in the
      lateral septum, preoptic area, mediobasal hypothalamus, and tuberomammillary
      nucleus, whereas kainate-2 subunit mRNA was abundant in the medial septum
      diagonal band, median and anteroventral preoptic nuclei, and supraoptic nuclei as
      well as the magnocellular portion of the posterior paraventricular nucleus.
      Regions that contained the highest levels of NMDAR1 subunit mRNA included the
      septum, the median preoptic nucleus, the anteroventral periventricular nucleus,
      and the supraoptic and suprachiasmatic nuclei as well as the arcuate nucleus.
      Together, the extensive distribution of the different GluR subunit mRNAs
      strengthen the view that glutamate is a major excitatory neurotransmitter in the
      hypothalamus. The overlap in the distribution of the various subunit mRNAs
      suggests that many neurons can express GluR channels that belong to different
      families, which would allow a differential regulation of the target neurons by
      glutamate.

PMID- 11329133
TI  - How well does the CSF inform upon pathology in the brain in Creutzfeldt-Jakob and
      Alzheimer's diseases?
AB  - Analysis of lumbar cerebrospinal fluid (CSF) plays a major role in the
      investigation of central nervous system disease, but how well do the changes in
      the CSF reflect pathology within the brain and spinal cord parenchyma? Both
      Creutzfeldt-Jakob (CJD) and Alzheimer's disease (AD) are characterized by the
      deposition of insoluble beta-pleated sheet peptides [prion protein (PrP) and beta
      amyloid (Abeta), respectively] in the extracellular spaces of grey matter in the
      brain, but there is discordance in both diseases between the peptide levels in
      the brain and in the CSF. Experimental studies using tracers have shown that
      interstitial fluid (ISF) drains through very narrow intercellular spaces within
      grey matter into bulk flow perivascular channels that surround penetrating
      arteries. ISF then flows to the surface of the brain and joins CSF to drain to
      cervical lymph nodes. Such drainage of ISF and CSF to regional lymph nodes in the
      rat plays a significant role in B-cell and T-cell immune reactions within the
      brain. In man, the pia mater separates the periarterial ISF drainage pathways
      from the CSF in the subarachnoid space. The almost complete lack of insoluble
      protease-resistant PrP entering the CSF from the brain in patients with CJD,
      reported by Wong et al. in this issue of the Journal of Pathology, illustrates
      the limitations of ISF drainage pathways for the elimination of insoluble
      peptides from brain tissue. Insoluble Abeta accumulates in the extracellular
      spaces as plaques in AD and in periarterial ISF drainage pathways as cerebral
      amyloid angiopathy. Soluble Abeta appears to become entrapped by the insoluble
      Abeta in the ISF drainage pathways; thus, as the level of soluble Abeta in the
      brain rises in AD, the level in the CSF falls. Thus, the changes in the CSF do
      not accurately reflect the accumulation of the abnormal peptides in the brain
      parenchyma in either CJD or AD. In both diseases, facilitation of ISF drainage
      and elimination of PrP and Abeta peptides from the extracellular spaces of the
      brain may lead to practical therapeutic strategies for these devastating
      disorders.

PMID- 11329134
TI  - Met protein and hepatocyte growth factor (HGF) in papillary carcinoma of the
      thyroid: evidence for a pathogenetic role in tumourigenesis.
AB  - In the last 10 years, evidence has accumulated that overexpression of Met protein
      is a distinguishing feature of almost every case of well-differentiated papillary
      carcinoma. Increased expression of the protein is probably due to enhanced
      transcription of the MET gene and/or to post-transcriptional mechanisms. So far,
      alterations of the MET gene have not been recognized, but evidence has been
      provided that activated RAS and RET can cause accumulation of MET RNA. Thus, the
      possibility exists that dysregulation of MET is the final result of different
      molecular pathways capable of inducing thyroid cell transformation; RET
      rearrangements might account for some of the cases, but the demonstration that
      the majority of papillary carcinomas do not have recognized alterations of the
      RET gene strongly suggests that MET gene dysregulation can also be achieved
      through other molecular pathways. Dysregulation of MET causes marked accumulation
      of Met protein in tumour cells that is promptly detected by immunohistochemistry.
      Thus, overexpression of Met protein might represent an immunohistochemical marker
      of papillary carcinoma, potentially helpful in problematic cases, but caution is
      required; moderate expression of Met protein is observed in non-neoplastic
      thyroid diseases, such as Graves' and Hashimoto's thyroiditis, and reagents
      active on paraffin sections may have a low affinity and/or low specificity for
      Met protein, leading to artifactual staining. Met protein-positive papillary
      carcinoma cells may produce hepatocyte growth factor (HGF) and may activate HGF
      through the urokinase-type plasminogen activator (uPA) bound to urokinase-type
      plasminogen activator receptor (uPA-R). Thus, papillary carcinoma cells possess
      the molecular machinery necessary for a productive HGF/Met interaction. In vitro
      studies have demonstrated that HGF enhances the motility and invasiveness of
      tumour cells and induces the synthesis and release of chemokines active in the
      recruitment of dendritic cells. These observations provide a rational basis for
      the understanding of two distinguishing features of papillary carcinoma. First,
      the tumour is often characterized by early metastatic spread to regional lymph
      nodes and by multifocal involvement of the gland, which suggests highly invasive
      behaviour. Second, a prominent peritumoural inflammatory reaction is often
      observed, which suggests cross-talk between tumour cells and the immune system.

PMID- 11329135
TI  - Absence of protease-resistant prion protein in the cerebrospinal fluid of
      Creutzfeldt-Jakob disease.
AB  - Creutzfeldt-Jakob disease (CJD), believed to be caused by a protease-resistant
      isoform of prion protein (PrP(Sc)), usually manifests itself as a clinically
      distinctive age-related dementia because of its rapid progression, occasionally
      accompanied by cerebellar ataxia. Recently, a variant CJD (vCJD) has been
      described, which has prominent early psychiatric symptoms and an earlier age of
      death. Although cerebrospinal fluid (CSF) is part of the extracellular fluid of
      the central nervous system (CNS), the bulk of its proteins are derived from the
      plasma and there is increasing concern about possible transmission of prion
      disease by blood. As investigation of CSF has played a significant role in the
      diagnosis and management of several neurological diseases, it was decided to
      characterize PrP present in the CSF of CJD individuals. Significant variation was
      observed in the level of PrP in the CSF from both non-CJD and CJD (including
      vCJD) patients, and the detected PrP forms are protease-sensitive. Using a
      conformation-dependent immunoassay, it was further demonstrated that the PrP
      detected in the CSF from CJD patients was broadly similar in conformation to that
      found in non-CJD patients. Taken together, the results of this study fail to
      demonstrate any correlation between the presence of protease-resistant PrP
      isoform (PrP(Sc)) in the CSF and disease manifestation.

PMID- 11329136
TI  - Increased expression of cFLIP(L) in colonic adenocarcinoma.
AB  - During tumour progression, cancer cells use diverse mechanisms to escape from
      apoptosis-inducing stimuli, which may include receptor internalization,
      inhibition of signal pathways, and regulation of specific sets of genes.
      Substantial numbers of colon cancer cells have been observed to express Fas/Fas
      ligand, but are resistant to Fas-mediated apoptosis, suggesting that colonic
      tumours might develop specific mechanisms to overcome Fas-mediated apoptosis.
      Recently, cellular FLICE-like inhibitory protein (cFLIP) has been identified as
      an endogenous inhibitor of Fas- or other receptor-mediated apoptosis and its
      altered high expression has a suspected association with tumour development or
      progression. In an effort to investigate the prevalence of cFLIP(L) alterations
      in colon carcinomas and their possible implications for the progression of colon
      cancers, cFLIP(L) expression was analysed in adenocarcinomas and adenomatous
      polyps of colon, with matched normal tissues, at RNA and protein levels, by semi
      quantitative reverse transcription-polymerase chain reaction (RT-PCR) and
      immunohistochemistry. cFLIP(L) transcripts were constitutively expressed in colon
      cancers and expression levels were significantly higher in carcinomas than in
      normal tissues (p<0.05). Overexpression of cFLIP(L) protein was found exclusively
      in carcinoma cells in all matched sets analysed and approximately three-fold
      induction was detected in cancer cells (p<0.05). The expression of cFLIP(L)
      protein was not significantly altered in adenomatous polyps compared with normal
      tissues. Taken together, these results strongly suggest that abnormal
      overexpression of cFLIP(L) is a frequent event in colon carcinomas and might
      contribute to in vivo tumour transformation.

PMID- 11329137
TI  - Expression of the E-cadherin-catenin complex in lung neuroendocrine tumours.
AB  - Neuroendocrine tumours (NETs) of the lung represent a wide spectrum of
      phenotypically distinct entities, with differences in tumour progression and
      aggressiveness. The redistribution and/or the loss of various cell adhesion
      molecules, such as the E-cadherin-catenin complex, play a predominant role in
      carcinogenesis and in tumour invasion. Moreover, mutations in exon 3 of the beta
      catenin gene, the adenomatous polyposis coli (APC) gene or the E-cadherin genes
      were previously found to result in intracytoplasmic and/or nuclear beta-catenin
      protein accumulation, activating nuclear transcription of target genes involved
      in tumour progression. In the present study, the distribution of the components
      of this E-cadherin-catenin complex has been investigated by immunohistochemistry
      and an attempt has been made to correlate the abnormal expression pattern with
      the eventual detection of mutations in the corresponding genes. This study
      included 27 primary NETs of the lung, with nine typical carcinoids (TCs), three
      atypical carcinoids (ACs), and 15 large cell neuroendocrine carcinomas (LCNECs).
      The E-cadherin-catenin complex remained expressed in most of these lung tumours,
      but with a cytoplasmic and/or nuclear redistribution of beta-catenin, E-cadherin,
      and alpha-catenin; abnormal positive immunoreactivity was observed in 24 (88.9%),
      in 21 (80.8%), and in 20 (76.9%) NETs, respectively. In the great majority of
      cases, there was a good correlation between the expression of these three
      proteins, but no significant association with histological classification or TNM
      stage. Thus, E-cadherin-complex redistribution cannot be considered a prognostic
      marker in NET of the lung. Of particular interest was the frequent focal beta
      catenin nuclear immunostaining (55.5% in total), which was also unrelated to
      histological type or TNM stage. However, this study failed to detect any mutation
      in exon 3 of the beta-catenin gene, in the APC gene or in the E-cadherin gene.
      These data suggest another mechanism of regulation of beta-catenin in these
      tumours.

PMID- 11329138
TI  - Altered intracellular localization of fibroblast growth factor receptor 3 in
      human breast cancer.
AB  - Immunohistochemical staining of human breast tissues, using an antibody against
      fibroblast growth factor receptor 3 [FGFR-3], showed differences in cellular
      distribution. Both malignant and non-malignant epithelial cells contained FGFR-3
      immunoreactivity, but myoepithelial cells and stroma were negative. The staining
      pattern in malignant epithelial cells was predominantly nuclear, whereas
      epithelial cells in normal breast tissue showed both cytoplasmic and nuclear
      elements. Reverse transcription-polymerase chain reaction (RT-PCR) revealed two
      isoforms of FGFR-3 corresponding to the FGFR-3-IIIb variant and a previously
      described exon-deleted nuclear form of FGFR-3, which were present in both
      malignant and non-malignant epithelial cells. The higher level of nuclear
      staining and loss of cytoplasmic staining seen in malignant epithelial cells did
      not correspond to an increase in expression of the exon-deleted form of FGFR-3,
      nor to any detectable activating point mutations. Since receptor activation can
      result in its movement to a perinuclear localization, an alternative explanation
      for the redistribution of FGFR-3-IIIb could be different degrees of activation by
      a ligand (FGF1 or FGF9). No FGF9 was detected by immunohistochemistry in breast
      tissues. FGF1, however, is present in the majority of breast cancers and a
      different tissue distribution of FGF1 was found in breast tissues, showing
      predominantly nuclear, or a mix of nuclear and cytoplasmic FGFR-3. The difference
      in FGFR-3 staining patterns may implicate this ligand-receptor pair in breast
      cancer.

PMID- 11329139
TI  - Differential expression of p16/p21/p27 and cyclin D1/D3, and their relationships
      to cell proliferation, apoptosis, and tumour progression in invasive ductal
      carcinoma of the breast.
AB  - In order to understand the intricate relationship of cell proliferation and
      apoptosis in tumour development, proliferation markers (Ki-67 and c-myc),
      apoptosis, cell-cycle inducers cyclin D1 and D3, and cell-cycle inhibitors
      p16(INK4), p21(CIP1), and p27(KIP1) were evaluated in ductal breast carcinoma.
      The heterogeneous nature of breast tumours provides a system by which the changes
      in cell-cycle genes can be explored under a wide range of proliferation and
      apoptotic indices. To address the above issues, immunohistochemical studies were
      conducted in 40 pairs of tumours and adjacent normal ductal tissues. The TUNEL
      method was used to identify apoptotic cells. Except for p27/KIP1, the
      proliferation (Ki-67, c-myc) and the apoptotic indexes together with levels of
      p16/INK4a, p21/CIP1, cyclin D1, and cyclin D3, were clearly elevated among tumour
      tissues, while absent in the adjacent normal tissues. Spearman correlation
      analysis indicated strong associations among apoptotic index, Ki-67, c-myc, and
      tumour grade. In addition, p21/CIP1 and cyclin D3 were positively correlated,
      while p16/INK4a, p27/KIP1, and cyclin D1 were negatively correlated with tumour
      grade. There was clear decoupling between p21 and p27, as well as decoupling
      between cyclin D1 and cyclin D3, in terms of their relationship to cell
      proliferation and apoptosis, indicating differential roles in tumour progression.

PMID- 11329140
TI  - The Ets-1 transcription factor is up-regulated together with MMP 1 and MMP 9 in
      the stroma of pre-invasive breast cancer.
AB  - The first steps of stroma generation are of pivotal importance for carcinogenesis
      because at this stage are initiated both angiogenesis, the prerequisite for
      continuous tumour growth, and the proliferation of stromal fibroblasts. These
      developments contribute to the onset of tumour invasion by secreting several
      matrix-degrading proteases. Both angiogenesis and the production of proteases are
      tightly controlled at several levels; of significant importance is transcription.
      The Ets-1 transcription factor transactivates several genes encoding matrix
      degrading proteases and is thought to be involved in both tumour vascularization
      and invasion. This study therefore investigated, by in situ hybridization and
      immunohistochemistry, the expression of Ets-1 and of two of its target genes,
      encoding matrix metalloproteinase (MMP) 1 and MMP 9, in order to demonstrate a
      topographical in vivo correlation between the expression of these three genes
      during breast cancer formation. All three genes were first expressed within both
      endothelial cells and stromal fibroblasts during the onset of stroma generation
      around intraductal and intralobular in situ carcinomas and they were
      significantly up-regulated in the stroma of invasive ductal and lobular cancers.
      The results of this study further support the suggested in vivo role of Ets-1 for
      both angiogenesis and tumour invasion, via matrix-degrading proteases which are
      already expressed during the early stages of breast carcinogenesis.

PMID- 11329141
TI  - Comparative analysis of human papillomavirus infections in cervical scrapes and
      biopsy specimens by general SPF(10) PCR and HPV genotyping.
AB  - Human papillomavirus (HPV) can be detected by DNA amplification from clinical
      samples. The aim of the present study was to compare the HPV status in both
      cervical scrape and biopsy specimens obtained from 174 patients, using the
      recently developed broad spectrum SPF(10) PCR-LiPA method. The detection rate of
      HPV in these materials was determined and the spectrum of HPV genotypes was
      compared. Cervical scrapes and biopsy specimens were obtained, either on the same
      day (group I), or with an interval of up to almost 2 years (group II, mean
      interval 97 days, range 1-469 days). HPV DNA was amplified by SPF(10) PCR and
      detected in a microtitre plate hybridization assay. Of the HPV-positive cases,
      the genotype was determined by reverse hybridization of the same SPF(10) amplimer
      on a line probe assay (LiPA), discriminating between HPV genotypes 6, 11, 16, 18,
      31, 33-35, 39, 40, 42-45, 51-54, 56, 58, 59, 66, 68, 70, and 74. The results
      showed that the detection rate and the spectrum of HPV genotypes in cervical
      scrapes and the corresponding biopsy specimens were highly comparable in both
      patient groups, even when multiple genotypes were present. In both groups,
      multiple HPV genotypes were more frequently detected in cervical scrapes than in
      the corresponding biopsy specimens. In conclusion, HPV infection can be diagnosed
      in cervical scrapes and biopsy specimens using the SPF(10) PCR-LiPA system.
      Analysis of cervical scrapes accurately reflects the spectrum of HPV genotypes in
      the patient's cervical region, even with a sampling interval between the cervical
      scrape and the biopsy specimen.

PMID- 11329142
TI  - Frequent nuclear beta-catenin accumulation and associated mutations in
      endometrioid-type endometrial and ovarian carcinomas with squamous
      differentiation.
AB  - Focal squamous differentiation is a common feature of endometrioid endometrial
      and ovarian carcinomas (E-Em and E-Ova Cas). A close association between mutated
      beta-catenin accumulation and alteration in cellular morphology has recently been
      demonstrated in murine L cell lines. To clarify the possible role of beta-catenin
      abnormalities and changes in tumour morphology, 60 grade (G) 1 or G2 E-Em Cas
      with areas of squamous differentiation (SqD), including morules and squamous
      metaplastic (SqM) foci, as well as 32 G1 or G2 tumours without such lesions, were
      investigated and the results compared with findings for c-jun and wnt-1
      expression. Twenty-three E-Ova Cas, with and without SqD lesions, were also
      examined. In E-Em Cas, frequent nuclear beta-catenin accumulation was observed in
      22 (84.6%) of 26 tumours with morules and 15 (45.5%) of 33 with SqM foci, in
      contrast to 4 (12.5%) of 32 without such lesions. Similar findings were also
      noted for mutations in exon 3 of the beta-catenin gene, involving codons 32, 33,
      34, 37, 41, and 45, the single nucleotide substitutions being identical between
      SqD and the surrounding carcinoma tissue in most informative cases. The mutations
      were positively related to nuclear immunopositivity, but inversely to membrane
      expression, while there was no association with the status of c-jun or wnt-1.
      These E-Ova Cas, nuclear beta-catenin accumulation and mutations were limited to
      tumours with SqD features, independent of c-jun and wnt-1 status. These data
      indicate that beta-catenin abnormalities are relatively common in E-Em and E-Ova
      Cas with SqD features, implying a role in the squamous differentiation of tumour
      cells, not necessarily related to c-jun and/or wnt-1 status.

PMID- 11329143
TI  - P53 mutation does not affect prognosis in ovarian epithelial malignancies.
AB  - Mutations of the p53 tumour suppressor gene have been found in most human
      cancers, including ovarian epithelial malignancies. This study investigated
      whether the presence or absence of p53 mutation was associated with outcome
      following platinum-based chemotherapy in patients with ovarian cancer. DNA
      samples from tumour tissue and blood were obtained from 73 patients with primary
      tumours, 50 of whom received platinum-based adjuvant chemotherapy. Single-strand
      conformation polymorphism analysis and direct DNA sequencing of exons 5-8
      detected mutations in 44% (32 of 73) of tumours. These were more common in late
      stage (III or IV) than in early-stage disease (I or II) (p=0.03). There was no
      association with histological type, volume of residual disease following surgery,
      or initial CA125 levels. No significant association was found between p53 status
      and overall survival or disease-free survival following chemotherapy. Likewise,
      there was no correlation between p53 mutation and response to chemotherapy as
      defined by normalization of CA125 levels. Tumours with p53 missense mutations
      recurred within a significantly shorter time than those with normal p53 (p=0.04).
      In addition, there was a tendency for tumours with missense mutations to have a
      shorter disease-free survival than those with non-missense mutations, although
      this did not reach statistical significance (p=0.07).

PMID- 11329144
TI  - The chromosome 9q genes TGFBR1, TSC1, and ZNF189 are rarely mutated in bladder
      cancer.
AB  - This study assessed a series of bladder tumours and bladder tumour cell lines for
      sequence variation in the Kruppel-like zinc finger gene ZNF189, the tuberous
      sclerosis complex gene 1 (TSC1), and the TGF beta receptor type I (TGFBR1). All
      three genes have been mapped to 9q regions commonly deleted in transitional cell
      carcinoma of the bladder. Mutation analysis of the coding sequence of these genes
      revealed several variant bands that were shown to represent polymorphisms.
      Mutation analysis of the ZNF189 gene in bladder cancer cell lines identified one
      amino acid substitution (lysine-->isoleucine) at position 323 in exon 4. For the
      TSC1 gene, two mutations were identified in two out of 27 independent cell lines.
      Both mutations result in a truncated protein. Furthermore, one out of 36 bladder
      tumours had a frameshift mutation in exon 7 of the TSC1 gene. No tumour-specific
      mutations were found in the TGFBR1 gene. The length of the polyalanine tract
      present in exon 1 of the TGFBR1 gene was also investigated. It has been suggested
      that the allele with six alanines (6A) is more frequent in patients with bladder
      and other cancers, so bladder cancer patients were compared with normal controls.
      In both groups, the percentage of heterozygotes was 17%. These data do not
      support a role for the 6A allele in bladder cancer susceptibility.

PMID- 11329145
TI  - Subtyping of oligo-astrocytic tumours by comparative genomic hybridization.
AB  - Oligo-astrocytic tumours (OAs) histologically show both oligodendroglial and
      astrocytic differentiation. Unequivocal criteria for delineation of OAs from pure
      oligodendroglial (Os) and astrocytic (As) tumours and for grading of OAs are
      lacking. Molecular genetic analysis may allow for a better characterization of
      OAs and thereby guide prognostic and therapeutic decisions. Comparative genomic
      hybridization (CGH) was performed on 39 gliomas with variable phenotypic
      expression of histological features characteristic of both astrocytic and
      oligodendroglial differentiation. The results show that OAs are genetically more
      heterogeneous than Os. In addition to the "-1p/-19q" and "+7/-10" subtypes that
      have been previously recognized, two additional genetic subtypes, "intermediate"
      and "other", were identified in the present study. "Intermediate" OAs likely
      represent progression from "-1p/-19q" tumours. The "other" subtype appears to
      represent an additional, heretofore unrecognized, genetic pathway(s). Application
      of rigorously "strict" histopathological criteria, as opposed to "relaxed"
      criteria, for the selection of oligo-astrocytic tumours resulted in a higher
      percentage of "-1p/-19q" tumours, but some "-1p/-19q" tumours might be missed.
      The results suggest that molecular genetic analysis is a useful and valid
      additional tool for the classification of gliomas, particularly for the
      significant subset of tumours in which subjective histopathological criteria are
      insufficient for an unequivocal distinction between Os, As, and mixed OAs.

PMID- 11329146
TI  - Expression of COL1A1-PDGFB fusion transcripts in superficial adult fibrosarcoma
      suggests a close relationship to dermatofibrosarcoma protuberans.
AB  - The diagnosis of fibrosarcoma has become relatively rare since the recognition
      and definition of certain adult spindle-cell sarcomas, such as monophasic
      synovial sarcoma, malignant peripheral nerve sheath tumour (MPNST), and malignant
      fibrous histiocytoma (MFH). Although most adult fibrosarcomas occur within intra-
      or inter-muscular fibrous tissues, some originate from superficial soft tissues
      (superficially located adult fibrosarcomas) (SAFs). Recently, the COL1A1-PDGFB
      chimeric gene resulting from a reciprocal translocation, t(17;22), and/or a
      supernumerary ring chromosome, r(17;22), has been identified, not only in
      conventional dermatofibrosarcoma protuberans (DFSP) but also in areas of DFSP
      with progression to fibrosarcoma (so-called fibrosarcomatous transformation) (FS
      DFSP). Since many SAFs are clinically and histologically similar to DFSP or FS
      DFSP, this study postulated that the two groups may be interrelated
      histogenetically. To test this hypothesis, a reverse transcription-polymerase
      chain reaction (RT-PCR) assay was conducted to determine whether COL1A1-PDGFB
      fusion transcripts could be detected in six cases of SAF, using archival formalin
      fixed, paraffin-embedded tissues. COL1A1-PDGFB fusion transcripts were detected
      in four of six SAFs, whereas no such fusion transcripts could be amplified in
      five deep-seated fibrosarcomas, eight congenital/infantile fibrosarcomas or 28
      other spindle-cell tumours and tumour-like lesions. These results show that at
      least some cases of SAF are genetically similar to DFSP and FS-DFSP, suggesting
      that some SAFs originate from DFSP or involve similar pathogenetic mechanisms.

PMID- 11329147
TI  - Expression of neurotrophins and their receptors in pigment cell lesions of the
      skin.
AB  - The neurotrophins (NTs) are a group of growth factors involved in the development
      of the nervous system and presumed to play a role in neural crest-derived
      tumours. The expression of three NTs (NGF, BDNF, and NT-3) and their receptors
      (NTRs; i.e. low-affinity pan-NT receptor p75, Trk-B, and Trk-C) was studied in
      frozen sections of benign and malignant cutaneous pigment cell lesions, using
      immunohistochemistry. In order to understand the possible role of these growth
      factors and their receptors in the progression of primary cutaneous malignant
      melanomas (PCMMs), their distribution in the radial (RGP) and vertical (VGP)
      growth phases was particularly studied. While most of the common acquired naevi
      were unreactive, Spitz and blue naevi showed scattered immunoreactive cells,
      especially for the p75 NTR. Dysplastic naevi, but not common naevi, expressed NT
      3 in their junctional component. PCMM and melanoma metastases often showed a
      diffuse pattern of immunostaining. NT-3 was significantly more frequently
      expressed in the RGP of PCMMs than in the junctional component of benign naevi,
      whereas more extensive immunoreactivity for NGF was found in the VGP of PCMMs,
      compared with the RGP; metastases more frequently expressed NGF, BDNF, and Trk-B
      than PCMMs. Interestingly, neurotropic melanoma expressed all NTs/NTRs except Trk
      B. These immuunohistochemical data confirm suggestions from previous in vitro
      studies that autocrine loops of certain NTs and their respective receptors may be
      involved in melanoma progression; in addition, NT-3 may be involved in the
      junctional growth of dysplastic naevi. The precise role of these growth factors
      in melanoma, however, will await further functional studies.

PMID- 11329148
TI  - The angiogenic pathway "vascular endothelial growth factor/flk-1(KDR)-receptor"
      in rheumatoid arthritis and osteoarthritis.
AB  - Active angiogenesis, together with an up-regulation of angiogenic factors, is
      evident in the synovium of both rheumatoid arthritis (RA) and osteoarthritis
      (OA). The present study assessed, by immunohistochemistry, the microvessel
      density in the synovium of these arthritides and in normal controls, in relation
      to the expression of the angiogenic factors vascular endothelial growth factor
      (VEGF) and platelet-derived endothelial cell growth factor (PD-ECGF) and the
      apoptosis-related proteins bcl-2 and p53. More importantly, using the novel 11B5
      MAb, the activated "VEGF/flk-1(KDR)-receptor" microvessel density was assessed.
      VEGF expression in fibroblasts was diffuse in both RA and OA. Diffuse PD-ECGF
      expression of fibroblasts was noted in all cases of RA, while fibroblast
      reactivity was focal in the OA material. The standard microvessel density (sMVD),
      as assessed with the anti-CD31 monoclonal antibody (MAb), was higher in RA (64+/
      12) and in OA (65+/-16) than in normal tissues (52+/-8; p=0.008 and 0.0004,
      respectively). The activated microvessel density (aMVD), assessed with the 11B5
      MAb, was significantly higher in RA (29+/-10) than in OA (17+/-4; p<0.0001) and
      than in normal tissues (14+/-2; p<0.0001). The "activation ratio" (aMVD/sMVD) was
      statistically higher in RA (0.46+/-0.17) than in OA and normal synovial tissues,
      the latter two having a similar ratio (0.28+/-0.08 and 0.26+/-0.03,
      respectively). Cytoplasmic bcl-2 expression was frequent in the synovial cells of
      OA, but rare in RA. Nuclear p53 protein accumulation was never observed. It is
      suggested that the angiogenic pathway VEGF/flk-1(KDR) may play an important role
      in the pathogenesis of RA and OA. Thus, failure of VEGF/flk-1(KDR) activation, in
      the presence of increased VEGF expression, may indicate a synovium with an
      impaired capacity to establish a viable vasculature, consistent with the
      degenerative nature of OA. On the other hand, the activated angiogenesis in RA
      shows a functional, still pathologically up-regulated VEGF/flk-1(KDR) pathway.
      Whether restoration of an impaired VEGF/flk-1(KDR) pathway in OA, or inhibition
      of this in RA, would prove of therapeutic importance requires further
      investigation.

PMID- 11329149
TI  - Targeted disruption of the nitric oxide synthase 2 gene protects against
      ischaemia/reperfusion injury to skeletal muscle.
AB  - To provide definitive insight into the complicated roles of the nitric oxide
      synthase (NOS) enzymes in ischaemia/reperfusion (I/R) injury of skeletal muscle,
      experiments were undertaken in mice with targeted disruption of the inducible NOS
      (NOS-2 KO) isoform, compared with the wild-type mouse strain. The degree of I/R
      injury in the NOS-2 KO mice was attenuated relative to that in the wild-type
      strain. After 70 min of ischaemia (24 h reperfusion), nitroblue tetrazolium (NBT)
      staining of skeletal muscle showed significant necrosis (40%) in wild-type mice,
      whilst in NOS-2 KO mice, ischaemia could be prolonged to 90 min before
      significant necrosis (38%) was apparent. Specific enzyme activities of the
      mitochondrial respiratory chain enzymes, measured in skeletal muscle homogenates,
      suggested that direct inhibition of the enzymes is not causal in the I/R injury.
      Immunohistological examination of skeletal muscle for NOS-2 showed its induction
      selectively in mast cells. In vitro experiments using bone marrow-derived mast
      cells showed that NOS-2 induction was associated with increased degranulation of
      mast cells. These findings suggest that NO generated by induction of NOS-2 has a
      deleterious effect in I/R injury of skeletal muscle and that NO exerts its
      damaging effect through factors released by degranulation of mast cells.

PMID- 11329150
TI  - Histopathological findings in skeletal muscle used in human dynamic
      cardiomyoplasty.
AB  - Patients submitted to dynamic cardiomyoplasty had an initial clinical improvement
      followed by a decrease in cardiac failure indices. A histopathological study of
      the skeletal muscle was undertaken to explain this. Latissimus dorsi fragments
      from 15 patients submitted to dynamic cardiomyoplasty in a 1:1 (heart beat:muscle
      stimulation) conditioning were analysed by light microscopy. The interval between
      surgery and obtaining the specimens (13 from necropsies, two from heart
      transplants) ranged from 37 days to 6 years. Nuclear clumps and internalization,
      the presence of round fibres, inflammation, and fibrosis were analysed semi
      quantitatively; the thickness of muscle fibres and the percentage of tissue fat
      were measured by image analysis. The quantitative data were also compared, in 12
      cases, with gender- and age-matched necropsy controls. The mean thickness of
      muscle fibres in cases and controls was 27.21+/-5.33 and 40.84+/-9.42 microm,
      respectively (p=0.001). The percentage of tissue fat in cases and controls was
      12.04+/-12.66% and 0.93+/-0.91%, respectively (p=0.008). The duration of grafts
      correlated positively with the quantity of nuclear clumps (R=0.80, p<0.001) and
      round fibres (R=0.53, p=0.04), as well as with the percentage of tissue fat
      (R=0.68, p=0.005). Accordingly, a negative correlation was found between the
      duration of grafts and the mean diameter of fibres, characterizing muscle atrophy
      (R=-0.66, p=0.01). The longer the post-surgical period, the more intense the
      degenerative lesions. This study shows that skeletal muscle used in human dynamic
      cardiomyoplasty may atrophy and be replaced by fat when stimulation is
      synchronized to every cardiac beat. These findings could play a role in
      explaining the long-term results of this surgical procedure.

PMID- 11329151
TI  - Chronic blockade of angiotensin II action prevents glomerulosclerosis, but
      induces graft vasculopathy in experimental kidney transplantation.
AB  - Long-term renin-angiotensin system blockade is beneficial in a variety of renal
      diseases. This study examines the long-term (34 weeks) effects of the angiotensin
      converting enzyme inhibitor lisinopril and the angiotensin II receptor type I
      blocker L158,809 in the Fisher to Lewis rat model of chronic renal transplant
      failure. Treatment in allografted rats with lisinopril or L158,809 was initiated
      10 days after transplantation, or at the time when proteinuria exceeded 50 mg/24
      h. Untreated allografts and syngrafts served as controls. In contrast to
      syngrafts, untreated allografts developed proteinuria, hypercholesterolaemia,
      interstitial damage, and glomerulosclerosis. Lisinopril or L158,809 treatment in
      allografts starting at day 10 after transplantation completely prevented this,
      with the exception of interstitial damage, but this treatment also caused a
      reduction in blood pressure and renal function. Moreover, the intimal surface
      area of the renal arteries was dramatically increased in allografts treated with
      either lisinopril or L158,809 compared with untreated allografted rats. Treatment
      once proteinuria had developed was less effective in preventing
      glomerulosclerosis, but also caused less intimal expansion. Thus, chronic renin
      angiotensin system blockade preserves glomerular morphology in the absence of
      proteinuria, but enhances intimal hyperplasia and reduces renal function in
      experimental transplantation. In view of these results, it should be questioned
      whether such treatment benefits renal transplant patients in the long term.

PMID- 11329152
TI  - A novel method for detecting HIV-1 by non-radioactive in situ hybridization:
      application of a peptide nucleic acid probe and catalysed signal amplification.
AB  - A novel in situ hybridization (ISH) method for detecting human immunodeficiency
      virus-1 (HIV-1) was developed by applying a peptide nucleic acid (PNA) probe and
      a catalysed signal amplification (CSA) method. The PNA probe used in the present
      study possessed 15 base sequences of the HIV-1 protease gene, and the 5' end of
      the probe was labelled with the fluorescein isothiocyanate (FITC) molecule. The
      hybridized probe was detected by sequential reactions of the following antibodies
      and reagents: horseradish peroxidase (HRP)-conjugated anti-FITC antibody,
      biotinylated tyramide (first amplification), HRP-labelled streptavidin,
      biotinylated tyramide (second amplification), and streptavidin-conjugated Alexa
      488. The signal of Alexa 488 was finally detected by fluorescence microscopy. HIV
      1-related dotted signals were clearly obtained in HIV-1 persistently infected
      cell lines, MOLT4-III(B) and ACH-2, and CD4-positive T lymphocytes from AIDS
      patients. For light microscopy, HRP-labelled streptavidin was reacted instead of
      streptavidin-conjugated Alexa 488 at the final treatment, followed by
      diaminobenzidine as chromogen. This method can detect HIV-1 in either blood smear
      samples or paraffin-embedded autopsy tissue and is useful as a sensitive non
      radioactive method for in situ hybridization.

PMID- 11329153
TI  - Prospective comparison of catheter-based endoscopic sonography versus standard
      endoscopic sonography: evaluation of gastrointestinal-wall abnormalities and
      staging of gastrointestinal malignancies.
AB  - PURPOSE: Endoscopic sonography (EUS) is an important imaging modality for
      evaluating benign and malignant luminal gastrointestinal-tract abnormalities. The
      objectives of this study were to evaluate the feasibility of catheter-based EUS
      (C-EUS) during standard upper and lower endoscopy in patients with malignancies
      and other abnormalities of the gastrointestinal-tract lumen, to assess the image
      quality obtained with the 12.5-MHz catheter-based ultrasound transducer, and to
      prospectively compare the interpretations of C-EUS images with those of the
      standard EUS (S-EUS) images. METHODS: One hundred thirty-seven consecutive
      patients referred for EUS were evaluated with C-EUS followed by S-EUS. The
      patients were assigned to 1 of 2 groups: group A, patients with intramural masses
      or intestinal wall thickening, with biopsies negative for malignancy; and group
      B, patients with esophageal, gastric, duodenal, or rectal cancer referred for
      staging. The results of C-EUS and S-EUS were compared for each group. RESULTS: C
      EUS was completed in 134 patients: 81 patients with 83 lesions in group A and 53
      patients in group B. For group A, C-EUS image interpretation concurred with that
      of S-EUS in 74 (89%) of 83 lesions. For group B, C-EUS concurred with S-EUS for
      tumor depth (T) and nodal (N) classifications in 19 cases (36%) and 26 cases
      (49%), respectively. The depth of invasion was underestimated by C-EUS in all 34
      cases in which the T classifications by C-EUS and S-EUS were discordant. In 1 of
      6 patients with stenotic cancer that was nontraversable by S-EUS, C-EUS
      identified lymphadenopathy (incorrectly classified as N0 by S-EUS). CONCLUSIONS:
      C-EUS was easily performed, and the C-EUS images were comparable to the S-EUS
      images in assessing mucosal and intramural lesions. The limited depth of
      penetration of the catheter-based transducer resulted in understaging the extent
      of tumor invasion and underestimating the nodal spread.

PMID- 11329154
TI  - Non-hodgkin's lymphoma of the liver in patients with AIDS: sonographic, CT, and
      MRI findings.
AB  - PURPOSE: We analyzed the sonographic, CT, and MRI findings in acquired immune
      deficiency syndrome (AIDS)-related non-Hodgkin's lymphoma (NHL) of the liver to
      evaluate the role of sonography in the diagnosis of this disease. METHODS: We
      retrospectively reviewed sonograms and CT scans on 26 patients who had human
      immunodeficiency virus with liver lymphoma, either primary (10 cases) or
      secondary (16 cases), from 1992 to 1999. We also reviewed MR images on 12 of the
      patients. All patients had pathologically proven NHL; all imaging studies were
      obtained within 2 weeks of sonographically guided fine-needle aspiration
      biopsies. Lymphoma was the initial AIDS-defining illness in 38% of the patients.
      RESULTS: NHL occurred as multiple lesions in most cases of both primary (7 of 10
      cases) and secondary (15 of 16 cases) liver lymphoma. No imaging finding was
      specific for the diagnosis of hepatic lymphoma. The hepatic lesions were
      hypoechoic in 25 of 26 cases; in the remaining case, there was a large isoechoic
      mass. On unenhanced and contrast-enhanced CT, the lesions were hypodense in all
      cases, with a thin enhancing rim in 6 patients. On MRI, the lesions were
      hypointense on T1-weighted images and hyperintense on T2-weighted images.
      CONCLUSIONS: Sonography may be helpful in the diagnosis of focal hepatic lymphoma
      in patients with human immunodeficiency virus. Sonographically guided fine-needle
      aspiration biopsy provides a definitive diagnosis. CT was crucial in the staging
      of lymphoma. MRI appears appropriate for studying liver NHL in selected cases.

PMID- 11329155
TI  - Doppler sonography of the inferior and superior mesenteric arteries in ulcerative
      colitis.
AB  - PURPOSE: The purpose of this study was to evaluate the Doppler sonographic blood
      flow parameters and spectral patterns in the inferior mesenteric artery (IMA) and
      superior mesenteric artery (SMA) in patients with active and inactive (remission
      phase) ulcerative colitis (UC). METHODS: The IMAs and SMAs of 25 patients with
      active-phase UC (group 1), 19 patients with remission-phase UC (group 2), and 22
      healthy, asymptomatic subjects (control group) were evaluated by duplex Doppler
      sonography. The 25 patients in group 1 were categorized into 2 subgroups on the
      basis of the extent of disease as determined by double-contrast barium enema x
      ray study and colonoscopy. The first subgroup (group 1a) consisted of 11 patients
      with active involvement of the left colon from the rectum to the splenic flexure.
      The second subgroup (group 1b) consisted of 14 patients with active involvement
      of the entire colon. The peak systolic velocity (PSV), end-diastolic velocity
      (EDV), mean velocity (Vmean), resistance index (RI), and pulsatility index (PI)
      were determined from the Doppler spectral analysis. The inner diameter and cross
      sectional area of the IMA and SMA were measured, and the blood-flow volume was
      calculated. The results were compared between the patient groups and control
      subjects. RESULTS: In the IMA, the mean blood-flow volume, mean PSV, mean EDV,
      and Vmean were significantly higher, the mean PI was significantly lower, and the
      mean diameter and the mean cross-sectional area were significantly larger in
      group 1 than in group 2 or in the control group (p < 0.001). The mean PSV and the
      Vmean of the IMA were significantly higher in group 1a than in group 1b (p <
      0.05). The mean blood-flow parameters in the SMA were not significantly different
      between groups 1 and 2 or between either group 1 or group 2 and the control
      subjects. The mean EDV in the SMA was significantly higher and the mean PI and
      the mean RI were significantly lower in group 1b than in group 1a (p < 0.01).
      CONCLUSIONS: Duplex Doppler sonography of the IMA and SMA can be used to evaluate
      inflammatory disease of the large bowel, to assess disease extent, and to
      document response to therapy.

PMID- 11329156
TI  - Gray-scale sonographic evaluation of cervical lymphadenopathy in cat-scratch
      disease.
AB  - PURPOSE: The aim of this study was to characterize the gray-scale sonographic
      findings in the lymph nodes of patients with cat-scratch disease (CSD). METHODS:
      We analyzed the sonograms of cervical lymph nodes in 41 patients with proven CSD
      between January 1997 and October 1999. RESULTS: A total of 222 involved lymph
      nodes were detected. Involved nodes were most commonly found in the middle
      cervical (58%), parotid (37%), upper cervical (37%), and submandibular (17%)
      regions. We found acute, chronic, or abscessed lymphadenopathy in 63%, 12%, and
      24% of patients, respectively. The size of involved lymph nodes ranged from 12 x
      4 mm to 35 x 26 mm. The largest involved node had a short axis/long axis ratio of
      0.5 or more in 61% of patients. Useful features for the differential diagnosis
      included markedly decreased echogenicity (100%), normal surrounding tissues
      (100%), and the presence of an echogenic hilum (76%). Posterior sound enhancement
      was significantly associated with larger and abscessed lymph nodes. CONCLUSIONS:
      Despite the absence of a specific sonographic finding for CSD, gray-scale
      sonography can provide clues to the diagnosis of CSD in the proper clinical
      setting.

PMID- 11329157
TI  - Abnormal fetal cerebral and umbilical Doppler measurements in fetuses with
      intrauterine growth restriction predicts the severity of perinatal morbidity.
AB  - PURPOSE: This prospective study was performed to determine if the ratio of the
      middle cerebral artery (MCA) S/D ratio (ratio of peak systolic blood flow
      velocity to diastolic velocity) to the umbilical artery (UA) S/D ratio (MCA/UA
      S/D ratio) predicts the degree of neonatal morbidity in fetuses suspected of
      having intrauterine growth restriction (IUGR). METHODS: Sixty-one fetuses were
      identified prospectively by sonography as having an estimated fetal weight below
      the 10th percentile for gestational age. The 61 fetuses underwent Doppler
      sonography in the third trimester and then were stratified into 3 groups based on
      the MCA/UA S/D ratio: group A, MCA/UA S/D ratio > 1.0 (controls; n = 37); group
      B, MCA/UA S/D ratio < or = 1.0 (intracerebral blood flow redistribution; n = 16);
      and group C, reversed or absent UA diastolic flow (n = 8). Outcome variables
      assessed included gestational age at delivery, birth weight, UA pH, mode of
      delivery, respiratory distress syndrome requiring intubation, and intracranial
      hemorrhage. RESULTS: The mean MCA/UA S/D ratios in groups A and B were 1.69 + /-
      0.61 and 0.59 + /- 0.24, respectively (p < 0.01). The mean gestational ages at
      delivery for groups A, B, and C were 34.7, 33.2, and 29.0 weeks, respectively.
      The mean birth weights were below the fifth percentile for age for groups B and C
      and significantly related to the severity of abnormal Doppler findings (p < 0.01)
      after correction for age. Mean UA pHs were 7.25 + /- 0.01, 7.19 + /- 0.01, and
      7.14 + /- 0.13 for groups A, B, and C, respectively, with significant differences
      between groups A and B (p < 0.05) and groups A and C (p < 0.05). Respiratory
      distress syndrome and intracranial hemorrhage were not associated with abnormal
      Doppler findings after correction for gestational age. The interval between the
      abnormal Doppler examination and delivery (p < 0.001) and the occurrence of fetal
      distress requiring cesarean section (p < 0.001) were significantly related to the
      severity of Doppler findings. CONCLUSIONS: In fetuses with suspected IUGR,
      abnormal MCA/UA S/D ratios are strongly associated with low gestational age at
      delivery, low birth weight, and low UA pH. Abnormal MCA/UA S/D ratios are also
      significantly associated with shorter interval to delivery and the need for
      emergent delivery.

PMID- 11329158
TI  - Doppler sonographic study of fetal brachial and umbilical artery blood flow
      during pregnancy.
AB  - PURPOSE: The purpose of this study was to evaluate the fetal brachial artery
      resistance index (RI), its changes throughout gestation, and its relationship to
      the umbilical artery RI. METHODS: One hundred fifty-four sonographic examinations
      of the brachial and umbilical arteries in 71 fetuses were performed between 12
      and 40 weeks' gestational age in 71 women with normal pregnancies. For each week
      of gestational age, the mean, standard deviation, range, and t-distribution 95%
      confidence interval of the fetal brachial artery RI were calculated. RESULTS: The
      fetal brachial artery RI, although relatively lower at the beginning of
      gestation, showed a pattern of high resistance, with a slight increase until
      term, whereas the fetal umbilical artery RI decreased progressively. CONCLUSIONS:
      The brachial artery RI is high in normal fetuses with good oxygenation. Umbilical
      artery RIs showed a progressive decrease until the end of term.

PMID- 11329159
TI  - Sonography for right lower quadrant pain.

PMID- 11329160
TI  - Gray-scale sonographic findings in a patient with pseudomyxoma peritonei.
AB  - Pseudomyxoma peritonei is a rare condition in which the abdominal cavity fills
      with thick mucoid material as a result of either a benign or malignant disease.
      We report the findings with gray-scale sonography and laparoscopy in a 74-year
      old man with pseudomyxoma peritonei. After paracentesis and drainage of the
      ascites, sonography visualized hypoechoic nodules in the peritoneum at the
      surface of the liver and between bowel loops. Laparoscopy revealed mucoid
      material diffusely throughout the abdominal cavity. The diagnosis of pseudomyxoma
      peritonei was confirmed by cytologic examination of peritoneal fluid and
      histologic examination of laparoscopically obtained specimens.

PMID- 11329161
TI  - Testicular epidermoid cysts: sonographic features with histopathologic
      correlation.
AB  - Testicular epidermoid cysts are rare, accounting for 1% of all testicular tumors.
      We present the sonographic appearances of epidermoid cysts in 3 cases, together
      with the histopathologic correlation. In case 1, sonography showed an
      intratesticular hypoechoic mass with a well-defined echogenic rim; the mass
      measured 1.8 x 1.5 x 1.5 cm, and there was no evidence of calcification. In case
      2, sonography showed a well-circumscribed mass measuring 1.3 x 1.3 x 1.0 cm, with
      alternating hypoechoic and hyperechoic rings (onion-ring appearance) and no
      calcifications. In case 3, sonography showed a 2.4- x 2.3- x 2.3-cm, well
      circumscribed, oval mass with a heterogeneous echotexture and an outer hypoechoic
      halo. The mass contained plaque-like regions of increased echogenicity, with
      peripheral acoustic shadowing from refraction artifact. Hypoechoic clefts were
      visualized posterior to the plaque-like areas. The triad of findings-sonographic
      appearance of an onion ring, avascularity on Doppler sonography, and negative
      results of tumor marker studies-is highly suggestive of an epidermoid cyst.

PMID- 11329162
TI  - Gray-scale and color Doppler sonographic diagnosis of epiploic appendagitis.
AB  - Depending on its location, epiploic appendagitis may mimic nearly any acute
      abdominal condition. We present the case of a patient with left lower quadrant
      pain. Sonography demonstrated an ovoid, hyperechoic, noncompressible lesion at
      the point of tenderness but no inflammatory changes in the adjacent colonic wall.
      Color Doppler sonography showed no flow in the lesion. Based on the sonographic
      diagnosis of epiploic appendagitis, conservative treatment was given, with
      complete recovery in 5 days. Awareness of these sonographic findings may aid in
      the early diagnosis of epiploic appendagitis and avoid unnecessary treatment.

PMID- 11329163
TI  - Sonographic and MRI findings in prepubertal adnexal hemorrhagic cyst with
      torsion.
AB  - Adnexal torsion is rare before menarche. We report the case of a 10-year-old girl
      with persistent left lower quadrant pain proven by surgery to be caused by
      adnexal torsion due to a hemorrhagic cyst. Sonography showed a well-defined,
      complex, predominantly solid mass with some sound through-transmission and a
      small amount of fluid. The left ovary could not be distinguished from the mass;
      the right ovary appeared normal. Doppler sonography demonstrated no blood flow
      within the mass. MRI revealed a circumferential region of high signal intensity
      in the periphery of the mass and multiple hyperintense foci in the left ovary.

PMID- 11329164
TI  - Health evaluation of translocated free-ranging primates in French Guiana.
AB  - Among over 40 mammal species threatened by the filling of a hydroelectric dam
      reservoir in French Guiana, three species of primates have been translocated,
      comprising 124 red howler monkeys, six white-faced sakis, and 95 golden-handed
      tamarins. Health status of the animals was evaluated by direct physical
      examination and by hematological, biochemical, virological, and parasitological
      surveys of collected blood. The physical condition of the howlers was slightly
      worse toward the end of the capture period, but that of sakis and tamarins
      remained satisfactory. Several ectoparasites (ticks, larvae of dipterous insects,
      fleas, and lice) were collected, and various wounds, apparently nondebilitating,
      were recorded in howlers. Hematological and biochemical profiles determined for
      the three species revealed a slight anemia in howlers. Entamoeba, Strongyloides,
      and Trypanoxyurus were common in fecal samples of howlers. A survey of blood
      smears from the three species revealed infection by several types of
      microfilaria, Trypanosoma rangeli-like and Plasmodium brasilianum in all three,
      and Trypanosoma cruzi-like in howlers. These infections had no significant impact
      on the health status or the hematological profiles. Serologic investigations
      revealed occasional reactions against Toxoplasma gondii, a strong anti-Plasmodium
      response in the two Cebidae species, and a weaker one in tamarins. Attempts to
      isolate arbovirus failed, but antibody responses to Mayaro and yellow fever
      viruses were strong, especially in the howlers. A strong correlation between age
      and serological status led to a better understanding of the epidemic cycles. Our
      survey indicates French Guianan primates are reservoirs for several
      anthropozoonoses, including malaria, Chagas disease, and arboviruses.

PMID- 11329165
TI  - Patterns of positional behavior in mixed-species troops of Callimico goeldii,
      Saguinus labiatus, and Saguinus fuscicollis in northwestern Brazil.
AB  - We present the results of a 4-month field investigation of positional behavior,
      vertical ranging, and species differences in limb proportions and body mass in a
      mixed-species troop of Saguinus fuscicollis, Saguinus labiatus, and Callimico
      goeldii in northwestern Brazil. Despite certain similarities in overall
      positional repertoire, patterns of positional behavior varied significantly
      between species. Travel in Callimico occurred principally in the lowest levels of
      the canopy, and was characterized by an exaggerated form of hindlimb-dominated
      bounding (bounding-hop), and leaping to and from vertical trunks (55.1% of
      leaps). In contrast, saddle-back tamarins traveled in the lower and middle levels
      of the canopy, and engaged in a range of leaping behaviors, including stationary
      leaps (37.3%), acrobatic leaps (31.3%), and trunk-to-trunk leaps (20%). Red
      bellied tamarins exploited the highest levels of the arboreal canopy. Travel in
      this species was dominated by quadrupedal bounding and acrobatic leaps (67% of
      leaps) that began and ended on thin, flexible supports. Species differences in
      positional behavior correlated with species differences in limb proportions and
      locomotor anatomy, and provide a framework for understanding niche partitioning
      in mixed-species troops of Saguinus and Callimico.

PMID- 11329166
TI  - Phylogeny of lion tamarins (Leontopithecus spp) based on interphotoreceptor
      retinol binding protein intron sequences.
AB  - The evolutionary relationships of the lion tamarins (Leontopithecus) were
      investigated using nuclear interphotoreceptor retinol binding protein (IRBP)
      intron sequences. Phylogenetic reconstructions strongly support the monophyly of
      the genus, and a sister relationship between the golden lion tamarin,
      Leontopithecus rosalia, and the black lion tamarin, L. chrysopygus, to the
      exclusion of the golden-headed lion tamarin, L. chrysomelas. The most
      parsimonious evolutionary reconstruction suggests that the ancestral lion tamarin
      and the common ancestor of L. rosalia and L. chrysopygus had predominantly black
      coats. This reconstruction is not consistent with a theory of orthogenetic
      evolution of coat color that was based on coat color evolution in marmosets and
      tamarins. An alternative reconstruction that is consistent with metachromism
      requires that ancestral lion tamarins had agouti hairs.

PMID- 11329167
TI  - Subspecific genetic differences in the saddle-back tamarin (Saguinus fuscicollis)
      postcranial skeleton.
AB  - Saddle-back tamarins (Saguinus fuscicollis) have been differentiated into
      subspecies based on coat color and facial morphology. Morphology of first
      generation genetic hybrids can provide an understanding of population differences
      and evolution that may otherwise be difficult to obtain. This study compares
      postcranial morphology in two hybrids of saddle-back tamarins (S. f. illigeri x
      S. f. lagonotus and S. f. illigeri x S. f. leucogenys) to the purebred
      subspecies. We examine whether postcranial morphology differs between the
      purebred subspecies and their hybrids, and whether hybrids exhibit heterosis
      indicative of genetic differences between the parental subspecies. Fifty
      postcranial dimensions, or traits, were measured on 287 S. fuscicollis skeletons.
      Measurements were corrected for sex differences and environmental differences
      (wild-derived or laboratory-born). Females were larger than males for most
      postcranial dimensions, especially in the pelvis. Significant environmental
      differences were found throughout the postcranial skeleton, with wild-derived
      animals generally larger than animals born in the laboratory. Significant
      heterosis was found for six postcranial traits in the S. f. illigeri x S. f.
      leucogenys cross, and heterosis was found for 15 postcranial traits in the S. f.
      illigeri x S. f. lagonotus cross. These results suggest that subspecies
      differences in skeletal morphology are generally due to genetic rather than
      environmental differences. The subspecies appear to represent geographic isolates
      that differ in gene frequencies and directional dominance for skeletal traits.

PMID- 11329168
TI  - Noninstrumented enzyme-linked immunosorbant assay for detection of early
      pregnancy in macaques.
AB  - A practical, noninstrumented enzyme-linked immunosorbant assay (NELISA) for the
      measurement of urinary monkey chorionic gonadotropin (mCG) has been developed for
      the detection of early pregnancy in macaque monkeys for use in both the
      laboratory and the field. Five rhesus monkeys (Macaca mulatta) and six crab
      eating monkeys (Macaca fascicularis) were tested for the presence of mCG in urine
      on gestational days (GDs) 12 to 35. The mCG NELISA detected pregnancy as early as
      GD 14, with an average earliest detection at GD 16.5 +/- 1.4 (n = 11). Out of 90
      tests, 27 false-negative and zero false-positive tests were obtained, for an
      accuracy of 70.0%. Without the aid of a spectrophotometer, the presence of mCG in
      pregnant monkey samples was indicated by a dark green color change. Nonpregnant
      monkey urine samples, on the other hand, exhibited no color change. These
      findings suggest that the simple, economical, and reliable urinary mCG NELISA may
      be useful for diagnosing early pregnancy in these and related species. Because
      capture and restraint are unnecessary for collecting urine samples, the mCG
      NELISA has widespread potential for confined and free-ranging animals.

PMID- 11329169
TI  - Carnitine-dependent metabolic activities in Saccharomyces cerevisiae: three
      carnitine acetyltransferases are essential in a carnitine-dependent strain.
AB  - L-carnitine is required for the transfer of activated acyl-groups across
      intracellular membranes in eukaryotic organisms. In Saccharomyces cerevisiae,
      peroxisomal membranes are impermeable to acetyl-CoA, which is produced in the
      peroxisome when cells are grown on fatty acids as carbon source. In a reversible
      reaction catalysed by carnitine acetyltransferases (CATs), activated acetyl
      groups are transferred to carnitine to form acetylcarnitine which can be shuttled
      across membranes. Here we describe a mutant selection strategy that specifically
      selects for mutants affected in carnitine-dependent metabolic activities.
      Complementation of three of these mutants resulted in the cloning of three CAT
      encoding genes: CAT2, coding for the carnitine acetyltransferase associated with
      the peroxisomes and the mitochondria; YAT1, coding for the carnitine
      acetyltransferase, which is presumably associated with the outer mitochondrial
      membrane, and YER024w (YAT2), which encodes a third, previously unidentified
      carnitine acetyltransferase. The data also show that (a) L-carnitine and all
      three CATs are essential for growth on non-fermentable carbon sources in a strain
      with a disrupted CIT2 gene; (b) Yat2p contributes significantly to total CAT
      activity when cells are grown on ethanol; and that (c) the carnitine-dependent
      transfer of activated acetyl groups plays a more important role in cellular
      processes than previously realised.

PMID- 11329170
TI  - Isolation and sequence of the MIG1 homologue from the yeast Candida utilis.
AB  - The Mig1p repressor from the food yeast Candida utilis has been isolated using a
      homologous PCR hybridization probe. This probe was amplified with two sets of
      degenerate primers designed on the basis of highly conserved motifs in the DNA
      binding region (zinc-finger domain) from yeast Mig1p and fungi CreA repressors.
      The cloned gene was sequenced and found to encode a polypeptide of 345 amino
      acids which shows significant identity with other yeast and fungus repressors in
      the DNA-binding domain and also with the yeast Mig1 proteins in the C-terminal
      region (effector domain). The MIG1 repressor gene from C. utilis was able to
      complement functionally the mig1 mutation of S. cerevisiae. The sequence
      presented here has been deposited in the EMBL data library under Accession No.
      AJ277830.

PMID- 11329171
TI  - Identification of Candida tropicalis HSR1, a gene of the heat-shock factor
      related family, which confers salt tolerance in Saccharomyces cerevisiae.
AB  - A genomic library of Candida tropicalis in a yeast multicopy plasmid has been
      screened for clones conferring salt tolerance upon transformation into S.
      cerevisiae. The best halotolerance clone contained an open reading frame encoding
      a predicted protein of 728 amino acids with homology to transcription factors of
      the heat-shock family. This novel gene was named HSR1 and is present in single
      copy in the C. tropicalis genome. Upon transformation into S. cerevisiae it
      increases the expression of ENA1, a major determinant of salt tolerance encoding
      a cation-extrusion pump. The sequence of CtHSR1 has been deposited in the EMBL
      data library under Accession No. AJ296093.

PMID- 11329172
TI  - Cytosolic redox metabolism in aerobic chemostat cultures of Saccharomyces
      cerevisiae.
AB  - Cytosolic redox balance has to be maintained in order to allow an enduring
      cellular metabolism. In other words, NADH generated in the cytosol has to be re
      oxidized back to NAD(+). Aerobically this can be done by respiratory oxidation of
      cytosolic NADH. However, NADH is unable to cross the mitochondrial inner membrane
      and mechanisms are required for conveying cytosolic NADH to the mitochondrial
      electron transport chain. At least two such systems have proved to be functional
      in S. cerevisiae, the external NADH dehydrogenase (Luttik et al., 1998; Small and
      McAlister-Henn, 1998) and the G3P shuttle (Larsson et al., 1998). The aim of this
      investigation was to study the regulation and performance of these two systems in
      a wild-type strain of S. cerevisiae using aerobic glucose- and nitrogen-limited
      chemostat cultures. The rate of cytosolic NADH formation was calculated and as
      expected there was a continuous increase with increasing dilution rate. However,
      measurements of enzyme activities and respiratory activity on isolated
      mitochondria revealed a diminishing capacity at elevated dilution rates for both
      the external NADH dehydrogenase and the G3P shuttle. This suggests that
      adjustment of in vivo activities of these systems to proper levels is not
      achieved by changes in amount of protein but rather by, for example,
      activation/inhibition of existing enzymes. Adenine nucleotides are well-known
      allosteric regulators and both the external NADH and the G3P shuttle were
      sensitive to inhibition by ATP. The most severe inhibition was probably on the
      G3P shuttle, since one of its member proteins, Gpdp, turned out to be
      exceptionally sensitive to ATP. The external NADH dehydrogenase is suggested as
      the main system employed for oxidation of cytosolic NADH. The G3P shuttle is
      proposed to be of some importance at low growth rates and perhaps its real
      significance is only expressed during starvation conditions.

PMID- 11329173
TI  - Pichia pastoris Pex14p, a phosphorylated peroxisomal membrane protein, is part of
      a PTS-receptor docking complex and interacts with many peroxins.
AB  - The peroxisomal protein import machinery plays a central role in the assembly of
      this organelle in all eukaryotes. Genes encoding components of this machinery,
      termed peroxins or Pex proteins, have been isolated and characterized in several
      yeast species and in mammals, including humans. Here we report on one of these
      components, Pex14p, from the methylotrophic yeast Pichia pastoris. Work in other
      organisms has shown that Pex14p is located on the cytoplasmic surface of the
      peroxisomal membrane and binds peroxisomal targeting signal (PTS) receptors
      carrying proteins bound for the peroxisomal matrix, results that have led to the
      hypothesis that Pex14p is a receptor-docking protein. P. pastoris Pex14p
      (PpPex14p) behaves like an integral membrane protein, with its C-terminus exposed
      on the cytosolic side of the peroxisomal membrane. PpPex14p complexes with many
      peroxins, including Pex3p (Snyder et al., 1999b), Pex5p, Pex7p, Pex13p, Pex17p,
      itself, and a previously unreported peroxin, Pex8p. A portion of Pex14p is
      phosphorylated, but both phosphorylated and unphosphorylated forms of Pex14p
      interact with several peroxins. The interactions between Pex14p and other
      peroxins provide clues regarding the function of Pex14p in peroxisomal protein
      import.

PMID- 11329174
TI  - Efficient expression, purification and characterization of mouse salivary alpha
      amylase secreted from methylotrophic yeast, Pichia pastoris.
AB  - We constructed a secretion vector of mouse salivary alpha-amylase, pPAM, using
      the AOX1 promoter-terminator and the secretion signal of 128 kDa pGKL killer
      protein, for an alternative yeast, Pichia pastoris. Taking advantage of multicopy
      insertion of the expression cassette and optimized growth conditions, we
      succeeded in highly efficient extracellular production (approximately 240
      microg/ml) of mouse alpha-amylase in the 10 ml scale by conventional flask
      culture: this efficiency was about 90-fold higher than that of Saccharomyces
      cerevisiae. Growth temperature of cells was critical for efficient production of
      alpha-amylase. P. pastoris transformants secreted both core-glycosylated and non
      glycosylated alpha-amylase molecules with a glycosylated:non-glycosylated ratio
      of about 20:80. Both glycosylated and non-glycosylated alpha-amylases were
      purified separately to apparent homogeneity. The signal sequence was correctly
      processed in both species, and the molecular masses of glycosylated and non
      glycosylated alpha-amylase were determined to be 58 600 and 56 300, respectively,
      by mass spectrometry. We further studied the outer chain glycosylation of
      engineered mouse alpha-amylase secreted by P. pastoris.

PMID- 11329175
TI  - Vectors and gene targeting modules for tandem affinity purification in
      Schizosaccharomyces pombe.
AB  - We describe the construction of tagging cassettes and plasmids for tandem
      affinity purification (TAP) of proteins in Schizosaccharomyces pombe. The tagging
      cassettes are designed for either carboxy- or amino-terminal tagging of proteins.
      The carboxyl terminal tags differ in that they contain either two or four repeats
      of IgG binding units. For tagging endogenous loci, the cassettes contain the kan
      MX6 module to allow for selection of G418-resistant cells. The amino-terminal
      tagging vectors allow for the regulated expression of proteins. Sz. pombe Cdc2p
      was chosen to test these new affinity tags. Several known binding proteins co
      purified with both Cdc2p-CTAP and N-TAP-Cdc2p, indicating the usefulness of these
      tags for the rapid purification of stable protein complexes from Sz. pombe.

PMID- 11329176
TI  - Alterations of the glucose metabolism in a triose phosphate isomerase-negative
      Saccharomyces cerevisiae mutant.
AB  - The absence of triose phosphate isomerase activity causes an accumulation of only
      one of the two trioses, dihydroxyacetone phosphate, and this produces a shift in
      the final product of glucose catabolism from ethanol to glycerol (Compagno et
      al., 1996). Alterations of glucose metabolism imposed by the deletion of the TPI1
      gene in Saccharomyces cerevisiae were studied in batch and continuous cultures.
      The Deltatpi1 null mutant was unable to grow on glucose as the sole carbon
      source. The addition of ethanol or acetate in media containing glucose, but also
      raffinose or galactose, relieved this effect in batch cultivation, suggesting
      that the Crabtree effect is not the primary cause for the mutant's impaired
      growth on glucose. The addition of an energy source like formic acid restored
      glucose utilization, suggesting that a NADH/energy shortage in the Deltatpi1
      mutant could be a cause of the impaired growth on glucose. The amount of glycerol
      production in the Deltatpi1 mutant could represent a good indicator of the
      fraction of carbon source channelled through glycolysis. Data obtained in
      continuous cultures on mixed substrates indicated that different contributions of
      glycolysis and gluconeogenesis, as well as of the HMP pathway, to glucose
      utilization by the Deltatpi1 mutant may occur in relation to the fraction of
      ethanol present in the media.

PMID- 11329177
TI  - Current awareness.
AB  - In order to keep subscribers up-to-date with the latest developments in their
      field, this current awareness service is provided by John Wiley & Sons and
      contains newly-published material on yeasts. Each bibliography is divided into 10
      sections. 1 Books, Reviews & Symposia; 2 General; 3 Biochemistry; 4
      Biotechnology; 5 Cell Biology; 6 Gene Expression; 7 Genetics; 8 Physiology; 9
      Medical Mycology; 10 Recombinant DNA Technology. Within each section, articles
      are listed in alphabetical order with respect to author. If, in the preceding
      period, no publications are located relevant to any one of these headings, that
      section will be omitted. (4 weeks journals - search completed 7th Mar. 2001)

PMID- 11329178
TI  - Neuroligin 3 is a vertebrate gliotactin expressed in the olfactory ensheathing
      glia, a growth-promoting class of macroglia.
AB  - The molecular mechanisms that drive glia-glial interactions and glia-neuronal
      interactions during the development of the nervous system are poorly understood.
      A number of membrane-bound cell adhesion molecules have been shown to play a
      role, although the precise nature of their involvement is unknown. One class of
      molecules with cell adhesive properties used in the nervous system is the serine
      esterase-like family of transmembrane proteins. A member of this class, a glia
      specific protein called gliotactin, has been shown to be necessary for the
      development of the glial sheath in the peripheral nervous system of Drosophila
      melanogaster. Gliotactin is essential for the development of septate junctions in
      the glial sheath of individual and neighboring glia. Mutations that remove this
      protein result in paralysis and eventually death due to a breakdown in the glial
      based blood-nerve barrier. To study the role of gliotactin during vertebrate
      nervous system development, we have isolated a potential vertebrate gliotactin
      homologue from mice and rat and found that it corresponds to neuroligin 3. Using
      a combination of RT-PCR and immunohistochemistry, we have found that neuroligin 3
      is expressed during the development of the nervous system in many classes of
      glia. In particular neuroligin 3 is expressed in the olfactory ensheathing glia,
      retinal astrocytes, Schwann cells, and spinal cord astrocytes in the developing
      embryo. This expression is developmentally controlled such that in postnatal and
      adult stages, neuroligin 3 continues to be expressed at high levels in the
      olfactory ensheathing glia, a highly plastic class of glia that retain many of
      their developmental characteristics throughout life.

PMID- 11329179
TI  - Isolated human astrocytes are not susceptible to infection by M- and T-tropic HIV
      1 strains despite functional expression of the chemokine receptors CCR5 and
      CXCR4.
AB  - Within the brain, HIV-1 targets the microglia and astrocytes. Previous studies
      have reported that viral entry into astrocytes is independent of CD4, in contrast
      to microglia. We aimed to determine whether chemokine receptors play a role in
      mediating CD4-independent HIV-1 entry into astrocytes. We found that embryonic
      astrocytes and microglial cells express CCR5, CCR3, and CXCR4 transcripts.
      Intracellular calcium levels in astrocytes were found to increase following
      application of RANTES, MIP-1beta (CCR5-agonist), SDF-1alpha (CXCR4-agonist), but
      not eotaxin (CCR3-agonist). In microglial cells, eotaxin was also able to
      modulate internal calcium homeostasis. CD4 was not present at the cell surface of
      purified astrocytes but CD4 mRNA could be detected by RT-PCR. Neither HIV-1(9533)
      (R5 isolate) nor HIV-1(LAI) (X4 isolate) penetrated into purified astrocytes. In
      contrast, mixed CNS cell cultures were infected by HIV-1(9533) and this was
      inhibited by anti-CD4 mAb in 4/4 tested cultures and by anti-CCR5 mAb in 2/4.
      Thus, the HIV-1 R5 strain requires CD4 to penetrate into brain cells, suggesting
      that CCR5 cannot be used as the primary receptor for M-tropic HIV-1 strains in
      astrocytes. Moreover, inconstant inhibition of HIV-1 entry by anti-CCR5 mAb
      supports the existence of alternative coreceptors for penetration of M-tropic
      isolates into brain cells.

PMID- 11329180
TI  - In vitro evaluation of reactive astrocyte migration, a component of tissue
      remodeling in glaucomatous optic nerve head.
AB  - In order to improve understanding of remodeling events in the glaucomatous optic
      nerve head, the migration of optic nerve head astrocytes was studied in vitro.
      Since elevated intraocular pressure is an important stress factor identified in
      glaucomatous eyes, optic nerve head astrocytes were incubated under physical
      stress created by elevated hydrostatic pressure. In addition, they were incubated
      in the presence of a chemical stimulus, lipolysaccharide (LPS). Migration of
      reactivated astrocytes in the presence of these stressors was examined using
      chambers in which cell migration through extracellular matrix-coated pores is
      only possible following proteolytic digestion of the matrix. We observed that the
      migratory ability of optic nerve head astrocytes was approximately 4-6 times
      greater following exposure to elevated hydrostatic pressure or LPS for up to 48
      h. Phosphoinositide 3-kinase, protein kinase C, and tyrosine kinase were found to
      be involved in the signal transduction for activated migration of optic nerve
      head astrocytes in response to elevated hydrostatic pressure or LPS. In addition,
      we observed that the stress-induced migration of optic nerve head astrocytes,
      which is accompanied by proteolytic degradation, resulted in the formation of
      culture cavities containing mucopolysaccharides. These in vitro findings provide
      a clearer understanding of the pathophysiologic mechanisms of characteristic
      tissue remodeling events that occur, in vivo, in the glaucomatous optic nerve
      head.

PMID- 11329181
TI  - Electrophysiological properties of rat retinal Muller (glial) cells in
      postnatally developing and in pathologically altered retinae.
AB  - Retinal glial Muller cells are characterized by dominant K(+) conductances. The
      cells may undergo changes of their membrane currents during ontogeny and gliosis
      as described in rabbit and man. Although the rat retina is often used in
      physiological experiments, the electrophysiology of rat Muller cells is less well
      studied. The aim of the present study was to characterize their membrane currents
      in postnatal development and in two models of retinal degeneration. Freshly
      isolated cells were subjected to whole-cell patch clamp recordings. During the
      first 4 weeks after birth of rats, their Muller cells displayed an increase in
      all membrane currents, particularly in the inward currents elicited at
      hyperpolarizing potentials. The decrease of the membrane resistance from more
      than 760 MOmega to less than 50 MOmega was accompanied by a shift of the zero
      current potential from about -20 mV to -80 mV, similar as earlier observed in
      developing rabbit Muller cells. These developmental changes were found in
      pigmented Brown Norway rats as well as in rats with inherited retinal dystrophy
      (RCS rats). Moreover, an infection of Lewis rats with the Borna disease virus
      caused substantial neuroretinal degeneration but did not result in a strong
      reduction of inward currents and of the zero current potential of the Muller
      cells. Thus, rat Muller cells fail to change their basic membrane properties in
      two different models of retinal pathology. This is in contrast to human and
      rabbit Muller cells, which have been shown to undergo dramatic changes of their
      membrane physiology in response to retinal diseases and injuries.

PMID- 11329182
TI  - 13C isotopomer analysis of glucose and alanine metabolism reveals cytosolic
      pyruvate compartmentation as part of energy metabolism in astrocytes.
AB  - After incubation of glial cells with both (13)C-labeled and unlabeled glucose and
      alanine, (13)C isotopomer analysis indicates two cytosolic pyruvate compartments
      in astrocytes. One pyruvate pool is in an exchange equilibrium with exogenous
      alanine and preferentially synthesizes releasable lactate. The second pyruvate
      pool, which is of glycolytic origin, is more closely related to mitochondrial
      pyruvate, which is oxidized via tri carbonic acid (TCA) cycle activity. In order
      to provide 2-oxoglutarate as a substrate for cytosolic alanine aminotransferase,
      glycolytic activity is increased in the presence of exogenous alanine.
      Furthermore, in the presence of alanine, glutamate is accumulated in astrocytes
      without subsequent glutamine synthesis. We suggest that the conversion of alanine
      to releasable lactate proceeds at the expense of flux of glycolytic pyruvate
      through lactate dehydrogenase, which is used for ammonia fixation by alanine
      synthesis in the cytosol and for mitochondrial TCA cycle activity. In addition,
      an intracellular trafficking occurs between cytosol and mitochondria, by which
      these two cytosolic pyruvate pools are partly connected. Thus, exogenous alanine
      modifies astrocytic glucose metabolism for the synthesis of releasable lactate
      disconnected from glycolysis. The data are discussed in terms of astrocytic
      energy metabolism and the metabolic trafficking via a putative alanine-lactate
      shuttle between astrocytes and neurons.

PMID- 11329183
TI  - AN2/NG2 protein-expressing glial progenitor cells in the murine CNS: isolation,
      differentiation, and association with radial glia.
AB  - During early neural development, the lineage specification of initially
      pluripotent progenitor cells is associated with proliferation, differentiation,
      and migration. Oligodendroglial progenitor cells migrate from their sites of
      origin to reach the axons that they will myelinate. We have described a cell
      surface protein, AN2, expressed by oligodendroglial progenitor cells in vitro and
      showed that antibodies against AN2 inhibited the migration of cultured primary
      oligodendroglial progenitor cells, suggesting that the AN2 antigen plays a role
      in their migration. Recently, results from MALDI mass spectroscopy showed that
      AN2 is the mouse homologue of the rat NG2 protein. In this study, we have
      analyzed cells staining with AN2 antibodies during development and in the adult
      murine central nervous system (CNS), carried out double stainings with antibodies
      against NG2, and investigated the differentiation potential of cells in vitro
      after isolation from early postnatal brain using AN2 antibodies. AN2 and NG2
      antibodies stained totally overlapping populations of cells in the CNS. AN2/NG2
      expressing cells in embryonic and postnatal brain expressed the PDGF-alpha
      receptor and in postnatal brain exhibited electrophysiological properties typical
      of glial progenitor cells. Cells isolated from early postnatal brain using AN2
      monoclonal antibody developed into oligodendrocytes in low serum medium or into
      astrocytes in the presence of fetal calf serum. In the embryonic spinal cord,
      cells staining with AN2 antibodies were found closely apposed to radial glial
      cells, suggesting that glial precursors, like neurons, may use radial glia as
      scaffolds for migration.

PMID- 11329184
TI  - Vasoactive intestinal polypeptide in neuroglia? Immunoelectron microscopic
      localization in astrocytes of the rat mesencephalon.
AB  - The dorsal region of the rat interpeduncular nucleus (IPN) was found highly
      immunoreactive for vasoactive intestinal polypeptide (VIP). This area appeared as
      a cap-like structure at the midcaudal level of the nucleus. Unlike other brain
      areas, however, VIP immunoreactivity within the "cap" appeared vaguely punctuate
      with no light microscopically identifiable cell structures. Ultrastructurally, a
      dense meshwork of VIP-immunopositive bouton-laden axons was revealed. Labeled
      neuronal perikarya were not encountered. Some lightly immunoreactive dendrites
      were observed. In addition, immunopositive glial profiles were frequently seen.
      Perikarya and numerous fine processes, occasionally perivascular, identified as
      astroglia by established ultrastructural criteria, exhibited VIP
      immunoreactivity. Constant feature of the peptide immunolocalization was the
      predilection for the intermediate filament bundles of astrocytic perikarya and
      processes. This was usually accompanied by a thick coating of the inner aspect of
      glial plasmalemma and, in perikarya, by highly reactive vesicular profiles. Glial
      immunopositive elements were never seen beyond the boundaries of the diffuse
      "cap." In view of the repertoire of metabolic, neurotrophic, and neuroprotective
      mechanisms in which VIP neurons are involved in conjunction with astroglia, the
      presence of VIP-immunoreactive astrocytes in a circumscribed area, confirms the
      heterogeneity of astrocyte populations.

PMID- 11329185
TI  - Neuronal signals regulate neurotrophin expression in oligodendrocytes of the
      basal forebrain.
AB  - Previous studies suggest that oligodendrocytes express trophic molecules,
      including neurotrophins. These molecules have been shown to influence nearby
      neurons. To determine whether neuronal signals may, in turn, affect
      oligodendrocyte-derived trophins, we examined regulation of nerve growth factor
      (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) mRNA
      expression in cultured oligodendrocytes of the basal forebrain. Neuronal signals
      had distinct effects on individual neurotrophins. KCl elicited increases in BDNF
      mRNA, but did not affect expression of NGF or NT-3. The cholinergic agonist,
      carbachol, increased expression of NGF, but did not affect expression of BDNF or
      NT-3. Glutamate elicited a decrease in BDNF, but did not affect expression of NGF
      or NT-3. This glutamate effect is not due to toxicity, since the number of total
      cells was unchanged, while the number of mature myelin basic protein positive
      (MBP+) cells increased. Our observations suggest that individual neuronal signals
      distinctly influence the trophic function of oligodendrocytes.

PMID- 11329186
TI  - A comparison of conventional spin-echo and fast spin-echo in the detection of
      multiple sclerosis.
AB  - Fast spin-echo (FSE) pulse sequences enable T2-weighted imaging in a fraction of
      the time required for T2-weighted conventional spin-echo (CSE) imaging. Due to
      concerns that the altered contrast characteristics of FSE may interfere with the
      visualization of multiple sclerosis (MS) lesions, the sensitivity of T2-weighted
      FSE sequences was compared to comparably weighted CSE sequences in the imaging of
      the brain in 100 patients with clinically suspected MS. The proton-density FSE
      sequence revealed more MS lesions than its CSE counterpart, while the T2-weighted
      CSE sequences were found to be more sensitive than the T2-weighted FSE sequence.
      Contrast-to-noise ratios and signal-to-noise ratios compared favorably between
      sequences. Overall, there was little difference in the specificity between FSE
      and CSE in the diagnosis of MS. The higher sensitivity and the reduction in time
      attainable through the use of FSE warrants its replacement of CSE when imaging
      the brain in patients with clinically suspected MS. J. Magn. Reson. Imaging
      2001;13:657-667.

PMID- 11329187
TI  - Language dominance assessment by means of fMRI: contributions from task design,
      performance, and stimulus modality.
AB  - We investigated the influence of different task demands, task designs, and
      presentation modalities on the functional MRI activation patterns during a
      language lateralization task in a group of 14 right-handed control subjects. A
      word classification task was presented as target task appropriate to evoke
      language-related activation in the inferior frontal gyrus (IFG). The choice of
      the contrasting baseline task was demonstrated to have a major impact on the
      functional outcome: While a fixation baseline elicited activations in the
      inferior frontal gyrus of both hemispheres, a nonsemantic perceptual control task
      helped to isolate the relevant target task of word classification. The modality
      of stimulus presentation did not influence the functional data: Auditory and
      visual presentation modes broadly evoked activations in similar brain regions
      during word classification. Minor differences in task performance and the side of
      the responding hand did not interfere with the functional activation patterns of
      the target task. On the basis of our results, a protocol of functional
      lateralization in the inferior frontal gyrus is suggested. J. Magn. Reson.
      Imaging 2001;13:668-675.

PMID- 11329188
TI  - Coronary artery imaging using contrast-enhanced 3D segmented EPI.
AB  - The purpose of the work was to evaluate the effectiveness of extracellular
      contrast media in improving MR coronary angiography using breath-hold segmented
      echo-planar imaging (SEPI). Two protocols were designed to optimize the inversion
      recovery-prepared contrast-enhanced SEPI method. In 15 healthy volunteers,
      significant improvements in signal-to-noise ratio (SNR), contrast-to-noise ratio
      (CNR), vessel sharpness, and length of visualization were observed post-contrast.
      The method with two targeted scans to cover the left and right arteries,
      respectively, following separate 20-mL contrast injections, was found to yield
      thinner slices and longer right coronary artery (RCA) visualization than a single
      scan following a 40-mL contrast injection without compromising SNR and CNR. In
      conclusion, extracellular contrast media substantially improves the delineation
      of coronary arteries with SEPI. J. Magn. Reson. Imaging 2001;13:676-681.

PMID- 11329189
TI  - Gadolinium-enhanced, vessel-tracking, two-dimensional coronary MR angiography:
      single-dose arterial-phase vs. delayed-phase imaging.
AB  - The purposes of our study were to investigate the benefits of using a single dose
      of an extracellular contrast agent for coronary magnetic resonance angiography
      (CMRA) and to determine the relative benefits of arterial-phase vs. delayed-phase
      image acquisition. The right coronary artery was imaged in 10 healthy adults
      using a breath-hold, two-dimensional fast gradient echo pulse sequence designed
      for vessel tracking (multiphase, multislice image acquisition). Pre- and
      postcontrast CMRA was performed. Postcontrast imaging consisted of arterial- and
      delayed-phase CMRA following a 15 mL bolus (single dose) of contrast media and of
      delayed-phase imaging following a cumulative 45 mL contrast dose (triple dose).
      Contrast-enhanced CMRA provided a significantly higher (P < 0.001) signal-to
      noise ratio (SNR) and contrast-to-noise ratio (CNR) than noncontrast CMRA. CNR
      was highest for single-dose arterial-phase CMRA (13.1 +/- 4.5) and triple-dose
      delayed-phase CMRA (13.0 +/- 4.8), followed by single-dose delayed-phase CMRA
      (8.4 +/- 3.5) and noncontrast CMRA (4.2 +/- 1.8). Single-dose arterial-phase CMRA
      provided the best visualization of the distal right coronary artery and was
      preferred for blinded physician assessments. We concluded that utilization of a
      single dose of extracellular contrast media improves CMRA, especially if timed
      for arterial-phase imaging. J. Magn. Reson. Imaging 2001;13:682-689.

PMID- 11329190
TI  - Visualization of flow patterns distal to aortic valve prostheses in humans using
      a fast approach for cine 3D velocity mapping.
AB  - The fluid dynamic performance of mechanical heart valves differs from normal
      valves and thus is considered related to late clinical complications in patients.
      Since flow patterns evolving around heart valves are complex in space and time,
      flow visualization based on time-resolved 3D velocity data might add important
      information regarding the performance of specific valve designs in vivo. However,
      previous cine 3D techniques for three-directional phase-contrast velocity mapping
      suffer from long scan duration and therefore might hamper assessment in patients.
      A hybrid 3D phase-contrast sequence combining segmented k-space acquisition with
      short EPI readout trains is presented with its validation in vitro. The technique
      was applied to study flow patterns downstream from a bileaflet aortic prosthesis
      in six patients. Navigator echoes were incorporated for respiratory motion
      compensation. Before flow visualization, spurious phase errors due to concomitant
      gradient fields and eddy currents were corrected. Flow visualization was based on
      particle paths and animated velocity vector plots. Dedicated algorithms for
      particle path integration were implemented to account for the considerable motion
      of the ascending aorta during the cardiac cycle. A distinct flow pattern
      reflecting the valve design was observed closest to the valve during early flow
      acceleration. Reverse flow occurred adjacent to high velocity jets and above the
      hinge housings. Later in systole, flow became confined to the central vessel area
      and reverse flow along the inner aortic curvature developed. Further downstream
      from the valve, flow patterns varied considerably among patients, indicating the
      impact of varying aortic anatomy in vivo. It is concluded that MR velocity
      mapping is a potential tool for studying 3D flow patterns evolving around heart
      valve prostheses in humans. J. Magn. Reson. Imaging 2001;13:690-698.

PMID- 11329191
TI  - Combined MR imaging and CFD simulation of flow in the human descending aorta.
AB  - A combined MR and computational fluid dynamics (CFD) study is made of flow in the
      upper descending thoracic aorta. The aim was to investigate further the potential
      of CFD simulations linked to in vivo MRI scans. The three-dimensional (3D)
      geometrical images of the aorta and the 3D time-resolved velocity images at the
      entry to the domain studied were used as boundary conditions for the CFD
      simulations of the flow. Despite some measurement uncertainties, comparisons
      between simulated and measured flow structures at the exit from the domain
      demonstrated encouraging levels of agreement. Moreover, the CFD simulation
      allowed the flow structure throughout the domain to be examined in more detail,
      in particular the flow separation region in the distal aortic arch and its
      influence on the downstream flow during late systole. Additional information such
      as relative pressure and wall shear stress, which could not be measured via MRI,
      were also extracted from the simulation. The results have encouraged further
      applications of the methods described. J. Magn. Reson. Imaging 2001;13:699-713.

PMID- 11329193
TI  - Accuracy of segmented MR velocity mapping to measure small vessel pulsatile flow
      in a phantom simulating cardiac motion.
AB  - The purpose of this study was to investigate the accuracy of conventional,
      segmented, and echo-shared MR velocity mapping sequences to measure pulsatile
      flow in small moving vessels using a phantom with simulated cardiac motion. The
      phantom moved either cyclically in-plane, through-plane, in- and through-plane,
      or was stationary. The mean error in average flow was -2% +/- 3% (mean +/- SD)
      for all sequences under all conditions, with or without background correction, as
      long as the region of interest (ROI) size was equal to the vessel cross-sectional
      size. Overestimation of flow as a result of an oversized ROI was less than 20%,
      and independent of field of view (FOV) and matrix, as long as the offset in angle
      between the imaging plane and flow direction was less than 10 degrees. Segmented
      velocity mapping sequences are surprisingly accurate in measuring average flow
      and render flow profiles in small moving vessels despite the blurring in the
      images due to vessel motion. J. Magn. Reson. Imaging 2001;13:722-728.

PMID- 11329192
TI  - Preferential arterial imaging using gated thick-slice gadolinium-enhanced phase
      contrast acquisition in peripheral MRA.
AB  - PURPOSE: To investigate the feasibility of preferential arterial imaging using
      gadolinium-enhanced thick-slice phase-contrast imaging. METHODS: Six healthy
      volunteers were studied using a peripheral-gated segmented k-space CINE phase
      contrast pulse sequence using four views per RR interval with flow encoding in
      the superior-inferior direction. Images at the level of the popiteal trifurcation
      were acquired postcontrast with different section thicknesses (4-8 cm) and VENC
      values (20-150 cm/sec), and phase-difference processing. RESULTS: The post
      gadolinium contrast-enhanced thick-slice phase-contrast acquisitions demonstrated
      the ability to visualize the tibio-peroneal (trifurcation) arteries, especially
      in systole. With MR contrast agents, the signal from blood is raised
      significantly above that of stationary tissue from T(1) shortening such that the
      partial volume artifact is reduced in thick-slice acquisitions. Furthermore, by
      selecting the VENC value as a function of the cardiac cycle, the noise floor can
      be raised to selectively suppress flow values less than that of the noise
      threshold, allowing better accentuation of arterial structures at systole.
      CONCLUSIONS: Thick-slice phase-contrast acquisition with phase-difference
      processing has been observed to reduce partial volume artifacts when an MR
      contrast agent substantially increases signal in the vasculature over that of
      normal background tissue. Preferential arterial images can be obtained by either
      increasing the VENC value to selectively suppress signal from slow flow in the
      veins or by subtracting the diastolic phase image from the peak systolic phase
      image. J. Magn. Reson. Imaging 2001;13:714-721.

PMID- 11329194
TI  - Laser-induced interstitial thermotherapy of liver metastases in an interventional
      0.5 Tesla MRI system: technique and first clinical experiences.
AB  - Laser-induced interstitial thermotherapy (LITT) surveyed by magnetic resonance
      imaging (MRI) has been shown to be effective in various applications. The laser
      treatment of colorectal liver metastases usually requires a separate device
      (e.g., ultrasound or CT) to position the laser applicator. In this study, we used
      an interventional 0.5 T MRI system, allowing both the navigation to the target
      tissue and on-line thermometry. Laser irradiation was performed using a near
      infrared laser source combined with a cooled laser light guide. We treated 20
      patients exhibiting a total of 58 colorectal liver metastases. Clinically
      relevant complications did not occur. No residual tumor was observed after laser
      irradiation in all metastases with a diameter below 2 cm. Metastases with a mean
      diameter between 2 and 3 cm demonstrated total necrosis in 71%, while in larger
      tumors this proportion decreased to 46% (diameter, 3-4 cm) and 30% (diameter, >4
      cm), respectively. We conclude that LITT, guided by the employed interventional
      MRI system, is feasible and safe. The results suggest a more aggressive
      treatment, especially for larger metastases. J. Magn. Reson. Imaging 2001;13:729
      737.

PMID- 11329195
TI  - Examination of intra-gastrointestinal tract signal elimination in MRCP: combined
      use of T(1)-shortening positive contrast agent and single-shot fast inversion
      recovery.
AB  - To examine the effects of removing the gastrointestinal signal in MR
      cholangiopancreatography (MRCP), investigations were carried out on the combined
      use of T(1)-shortening intestine-positive contrast medium, FerriSeltz with ferric
      ammonium citrate as the main component, and high-speed imaging using single-shot
      fast inversion recovery (SSFIR). The contrast effect was significantly elevated
      to 10.2 +/- 1.6 after administration, compared with 5.9 +/- 2.4 before
      administration (P < 0.001). The enhancement effect was also significantly
      elevated to 13.2 +/- 3.0 after administration, compared with 4.9 +/- 3.1 before
      administration (P < 0.001). These results were obtained because the null point of
      FerriSeltz aqueous solution (5.97 mmol/L) was in the range of approximately 180
      msec. With the present method, adequate suppression of the signal intensity of
      the digestive tract was obtained relatively easily with MRCP, and the technique
      was found to be effective. J. Magn. Reson. Imaging 2001;13:738-743.

PMID- 11329196
TI  - Changes in intrarenal oxygenation as evaluated by BOLD MRI in a rat kidney model
      for radiocontrast nephropathy.
AB  - The pathogenesis of radiocontrast nephropathy is poorly understood. In an animal
      model, inhibition of the synthesis of nitric oxide and prostaglandins appears to
      predispose rats to severe renal injury following the administration of
      radiocontrast. Here we have investigated whether administration of radiocontrast,
      as well as changes in renal medullary oxygenation following pharmacologic
      inhibition of nitric oxide and prostaglandin synthesis, might be evaluated by
      blood oxygenation level-dependent (BOLD) MRI. Nineteen anesthetized (Inactin 100
      mg/kg) rats were studied. BOLD MRI measurements were performed following
      administration of L-NAME (N-nitro-L-arginine methyl ester, 10 mg/kg),
      Indomethacin (10 mg/kg), and a radiocontrast agent (sodium iothalamate 60%, 6
      mL/kg). Marked sequential changes in medullary R(*)(2), presumably reflecting
      decline in medullary pO(2), were noted after each of the pharmacological
      interventions employed. These results, obtained by noninvasive MRI, are
      consistent with prior direct recordings of pO(2) and doppler flow in the rat
      renal medulla after administration of L-NAME, Indomethacin and iothalamate.
      Medullary oxygenation in rats was reduced by inhibition of the synthesis of
      prostaglandins and nitric oxide, as well as by intravenous injection of
      radiocontrast agents. BOLD MRI can noninvasively evaluate changes in medullary
      oxygenation in rats that appear to predispose acute renal failure. J. Magn.
      Reson. Imaging 2001;13:744-747.

PMID- 11329197
TI  - Dynamic MR imaging and stress testing in glenohumeral instability: comparison
      with normal shoulders and clinical/surgical findings.
AB  - Our objectives were to test the hypotheses that: 1) during shoulder motion,
      glenohumeral alignment differs between asymptomatic shoulders and those with
      symptomatic instability; 2) during magnetic resonance (MR)-monitored physical
      exam or stress testing, glenohumeral alignment differs between asymptomatic
      shoulders and those with instability; and 3) glenohumeral translation during MR
      stress testing correlates with findings of shoulder instability by clinical exam
      and exam under anesthesia (EUA). Using an open-configuration 0.5 T MR imaging
      (MRI) system, we studied symptomatic shoulders in 11 subjects and compared them
      to their contralateral asymptomatic shoulders. Each shoulder was studied during
      abduction/adduction and internal/external rotation to determine the humeral head
      position on the glenoid. An examiner also performed the MR stress test on each
      shoulder by applying manual force on the humeral head during imaging. All
      shoulders were assigned an instability grade from the MR stress test, and this
      grade was correlated with: 1) clinical exam grade assigned during preoperative
      assessment by an orthopedic surgeon and 2) intraoperative instability grade by
      EUA immediately preceding arthroscopy. With dynamic abduction and
      internal/external rotation, the humeral head remained centered on the glenoid in
      9 of 11 shoulders, but in two subjects there were dramatic demonstrations of
      subluxation. With stress testing, a trend toward more joint laxity was
      demonstrated in symptomatic than in asymptomatic joints (P = 0.11). MR grading of
      instability correlated directly with clinical grading in six cases and
      underestimated the degree of instability relative to clinical exam in the other
      cases. MR instability grading systematically underestimated instability compared
      with EUA in 7 of the 10 cases that underwent surgical repair. We concluded that
      dynamic MR evaluation of glenohumeral alignment did not demonstrate abnormalities
      in symptomatic shoulders in 8 of 10 patients, whereas 2 patients showed dramatic
      findings of subluxation. Manual stress testing during dynamic MR examination
      showed a strong correlation with clinical instability grading. Dynamic shoulder
      MR examination during stress testing could, with further validation, become a
      useful adjunct to shoulder instability evaluations. J. Magn. Reson. Imaging
      2001;13:748-756.

PMID- 11329198
TI  - Relationship between bone marrow cellularity and apparent diffusion coefficient.
AB  - This study was performed to determine if there is a relationship between apparent
      diffusion coefficient (ADC) and cellularity of bone marrow of the posterior
      ilium. Four groups of various marrow cellularity underwent diffusion-weighted
      echo-planar imaging: 1) adults with normal hypocellularity (21 patients); 2)
      adults with normal normocellularity (13 patients); 3) young children with normal
      hypercellularity (5 patients); and 4) adults with lymphoma-related
      hypercellularity (3 patients). In all adults, marrow cellularity was confirmed by
      uni-or bilateral bone marrow biopsies. In children, the iliac marrow was presumed
      hypercellular because of their ages. A total of 66 ADC values of bone marrow
      calculated from diffusion-weighted images with b-values of 30 and 300
      seconds/mm(2) was evaluated. Hypercellular marrow (normal and lymphoma-related)
      showed the highest mean ADC, and hypocellular the lowest ADC. Statistically
      significant differences were found between three groups of normal marrow:
      hypocellular, normocellular, and hypercellular. There is a positive correlation
      between ADC and cellularity of bone marrow. J. Magn. Reson. Imaging 2001;13:757
      760.

PMID- 11329199
TI  - MR-guided biopsy of musculoskeletal lesions in a low-field system.
AB  - Thirty magnetic resonance (MR)-guided biopsies were obtained from 20 skeletal and
      10 soft-tissue lesions in 31 patients using an open 0.2 T MR system equipped with
      interventional accessories. The results from aspiration (N = 3), core biopsy (N =
      15), and transcortical trephine biopsy (N = 12) were evaluated for accuracy and
      clinical efficacy. Specimens were successfully obtained from 29 patients. Results
      were clinically effective in 23 patients, rated definitive in 16, nonconclusive
      in 9, and unspecific in 2 patients. A false diagnosis due to sampling error
      occurred in 2 patients, and biopsy sampling was impossible in one case. The best
      diagnostic yield was achieved from nontranscortical biopsies of osteolytic or
      soft-tissue masses. Results from transcortical biopsies were less specific due to
      the predominance of benign lesions. MR fluoroscopy for needle guidance was
      applied in 13 patients. Complete needle placement inside the magnet could be
      performed in 16 patients. MR-guided biopsy using an open low-field MR imager is
      feasible and clinically effective and will become a valuable tool in the
      management of musculoskeletal lesions. J. Magn. Reson. Imaging 2001;13:761-768.

PMID- 11329200
TI  - Comparison of gradient encoding schemes for diffusion-tensor MRI.
AB  - The accuracy of single diffusion tensor MRI (DT-MRI) measurements depends upon
      the encoding scheme used. In this study, the diffusion tensor accuracy of several
      strategies for DT-MRI encoding are compared. The encoding strategies are based
      upon heuristic, numerically optimized, and regular polyhedra schemes. The
      criteria for numerical optimization include the minimum tensor variance (MV),
      minimum force (MF), minimum potential energy (ME), and minimum condition number.
      The regular polyhedra scheme includes variations of the icosahedron. Analytical
      comparisons and Monte Carlo simulations show that the icosahedron scheme is
      optimum for six encoding directions. The MV, MF, and ME solutions for six
      directions are functionally equivalent to the icosahedron scheme. Two commonly
      used heuristic DT-MRI encoding schemes with six directions, which are based upon
      the geometric landmarks of a cube (vertices, edge centers, and face centers), are
      found to be suboptimal. For more than six encoding directions, many methods are
      able to generate a set of equivalent optimum encoding directions including the
      regular polyhedra, and the ME, MF and MV numerical optimization solutions. For
      seven directions, a previously described heuristic encoding scheme (tetrahedral
      plus x, y, z) was also found to be optimum. This study indicates that there is no
      significant advantage to using more than six encoding directions as long as an
      optimum encoding is used for six directions. Future DT-MRI studies are necessary
      to validate these observations. J. Magn. Reson. Imaging 2001;13:769-780.

PMID- 11329201
TI  - Partial left ventriculectomy in severe idiopathic dilated cardiomyopathy:
      assessment of short-term results and their impact on late survival by magnetic
      resonance imaging.
AB  - We evaluated short-term effects of partial ventriculectomy on left ventricular
      (LV) parameters and its impact on late survival by magnetic resonance imaging
      (MRI). Twenty patients and 10 normal volunteers were studied, and LV volumes
      (EDV, ESV), ejection fraction (EF), short- and long-axis dimensions (SA, LA),
      wall thickness (Wth), shape (LA/SA), geometry (Wth/SA), a geometry index (Phi),
      and wall-motion score index (WMSI) were evaluated pre- and postoperatively. Also,
      we compared results and survival of patients with preoperative EF <or=17% vs. EF
      >17%. Short-term results showed significant changes (P < 0.001) in: EF (17.3 +/-
      7.3% vs. 30.4 +/- 9.5%), EDV (391.9 +/- 118 vs. 272.7 +/- 90 mL); ESV (308.2 +/-
      102.8 vs. 190.3 +/- 68.4 mL); SA (80.5 +/- 10.4 vs. 71.7 +/- 7.8 mm); LA/SA (1.13
      +/- 0.1 vs. 1.34 +/- 0.1); Wth (8.35 +/- 0.99 vs. 9.75 +/- 1.41 mm); Wth/SA (0.10
      +/- 0.01 vs. 0.14 +/- 0.02), diastolic( 0.80 +/- 0.16 vs. 0.58 +/- 0.13) and
      systolic (0.78 +/- 0.18 vs. 0.55 +/- 0.12) Phi; and WMSI (-2 vs. -1) (P = 0.032).
      The EF division showed differences in: LA/SA (1.26 +/- 0.10 vs. 1.49 +/- 0.12) (P
      < 0.001); Wth/SA (0.13 +/- 0.02 vs. 0.15 +/- 0.02) (P = 0.023); diastolic (0.65
      +/- 0.11 vs. 0.48 +/- 0.11) and systolic (0.63 +/- 0.09 vs. 0.46 +/- 0.09) Phi (P
      < 0.001); and WMSI (-2 vs. -1) (P = 0.033). Finally, correlation between
      pre/postoperative EF showed for EF < 17%, r = 0.32 and for EF >17%, r = 0.83,
      which had different late survival. Our study showed significant changes on LV
      parameters after ventriculectomy. Patients with EF >17% showed better EF
      correlation between pre/postoperative values and higher survival rate. J. Magn.
      Reson. Imaging 2001;13:781-786.

PMID- 11329202
TI  - Fast (13)C-glucose metabolite mapping in rat brain using (1)H echo planar
      spectroscopic imaging technique at 2T.
AB  - For fast (13)C metabolite mapping in rat brains, (1)H-detected (13)C NMR
      spectroscopy using gradient-enhanced heteronuclear multiple-quantum coherence and
      (1)H echo planar spectroscopic imaging were combined. (13)C glucose and 3-/4
      (13)C-Glu/Gln images of rat brain were successfully constructed with 35-minute
      temporal resolution under a 2T magnetic field. In the ischemic region of the
      suture middle cerebral artery occlusion model, glucose and Glu/Gln signals
      decreased and lactate signals appeared. J. Magn. Reson. Imaging 2001;13:787-791.

PMID- 11329203
TI  - Virtual endoscopy of the labyrinth, using a 3D-FastASE sequence.
AB  - Virtual endoscopy (VE) of the labyrinth was performed using three-dimensional
      (3D)-fast asymmetric spin-echo MR imaging. The spatial resolution requirements
      and the usefulness of zero-fill interpolation (ZIP) were evaluated, and VE was
      used to examine three patients. The (0.6-mm) voxel data with ZIP satisfies the
      minimum requirements for VE for evaluation of the complex 3D anatomy and
      pathology of the labyrinth. J. Magn. Reson. Imaging 2001;13:792-796.

PMID- 11329204
TI  - Determination of arterial input function using fuzzy clustering for
      quantification of cerebral blood flow with dynamic susceptibility contrast
      enhanced MR imaging.
AB  - An accurate determination of the arterial input function (AIF) is necessary for
      quantification of cerebral blood flow (CBF) using dynamic susceptibility contrast
      enhanced magnetic resonance imaging. In this study, we developed a method for
      obtaining the AIF automatically using fuzzy c-means (FCM) clustering. The
      validity of this approach was investigated with computer simulations. We found
      that this method can automatically extract the AIF, even under very noisy
      conditions, e.g., when the signal-to-noise ratio is 2. The simulation results
      also indicated that when using a manual drawing of a region of interest (ROI)
      (manual ROI method), the contamination of surrounding pixels (background) into
      ROI caused considerable overestimation of CBF. We applied this method to six
      subjects and compared it with the manual ROI method. The CBF values, calculated
      using the AIF obtained using the manual ROI method [CBF(manual)], were
      significantly higher than those obtained with FCM clustering [CBF(fuzzy)]. This
      may have been due to the contamination of non-arterial pixels into the manually
      drawn ROI, as suggested by simulation results. The ratio of CBF(manual) to
      CBF(fuzzy) ranged from 0.99-1.83 [1.31 +/- 0.26 (mean +/- SD)]. In conclusion,
      our FCM clustering method appears promising for determination of AIF because it
      allows automatic, rapid and accurate extraction of arterial pixels. J. Magn.
      Reson. Imaging 2001;13:797-806.

PMID- 11329205
TI  - Real-time black-blood MRI using spatial presaturation.
AB  - A real-time interactive black-blood imaging system is described. Rapid blood
      suppression is achieved by exciting and dephasing slabs outside the imaging slice
      before each imaging excitation. Sharp-profiled radio frequency saturation pulses
      placed close to the imaging slice provide good blood suppression, even in views
      containing slow through-plane flow. In vivo results indicate that this technique
      improves endocardial border definition during systole in real-time cardiac wall
      motion studies. Phantom and animal results indicate that this technique nearly
      eliminates flow artifacts in real-time intravascular studies. J. Magn. Reson.
      Imaging 2001;13:807-812.

PMID- 11329206
TI  - Year 2000 status of MRI in Mexico.
AB  - The development of clinical magnetic resonance imaging in Mexico has followed a
      different course from that in the U.S. and Europe. The first clinical unit was
      installed in Mexico in the late 1980s at the very beginning of clinical
      applications worldwide. Since then, installations have proceeded at a sedate pace
      that now brings the installed total to 66 imagers. The largest fraction of these
      units (28, or 42%) is in Mexico City, with a broad distribution across the
      remaining 23 Mexican states. There is a noticeable increase of the number of
      units (20, or 30%) in the states bordering the U.S., while the states bordering
      nations to the south have no units. More than half the units (38, or 58%) are 0.5
      T units, while a further 35% are 1.0 T or higher. Slower addition of units in
      Mexico relative to the U.S. is attributed to the higher fraction of public-funded
      hospitals and the inherent conservatism of such institutions when considering new
      technologies. Present public planning for health care development suggests that
      the coming decade will see more rapid installation of units to meet growing
      demand in Mexico for the latest medical technology. Experience over the past two
      decades indicates the need for more systematic training of technical and clinical
      personnel to implement these additions. The National University (Universidad
      Nacional Autonoma de Mexico (UNAM) and the Metropolitan University (Universidad
      Autonoma Metropolitana (UAM) are collaborating with diverse clinical facilities
      to create such a program. J. Magn. Reson. Imaging 2001;13:813-817.

PMID- 11329208
TI  - Membrane-covered stents: a new treatment strategy for saphenous vein graft
      lesions.
AB  - The restenosis rate after stenting of lesions in aortocoronary venous bypass
      grafts still has to be considered unsatisfactorily high. We investigated a new
      stent design characterized by an expandable polytetrafluorethylene (PTFE)
      membrane in between two layers of struts. Five consecutive male patients (age 70
      +/- 6 years) were followed prospectively who presented with at least two de novo
      lesions in different grafts 13 +/- 3 years after bypass surgery. A total of 11
      lesions were treated located in grafts anastomosed to the circumflex (n = 3), to
      the LAD (n = 7), and to the right coronary artery (n = 1). Within the same
      procedure, every patient received membrane-covered stents (n = 6) and
      conventional stents (n = 5) in either of their lesions. All patients underwent
      successful interventions. The minimal luminal diameter increased from 1.0 +/- 0.5
      to 2.9 +/- 0.6 mm in lesions treated by the membrane-covered stents and from 0.8
      +/- 0.4 to 2.4 +/- 0.7 mm in the lesions treated by conventional stents. During
      follow-up, four out of five patients required angioplasty for in-stent restenosis
      of lesions covered by a conventional stent, whereas no patient underwent
      revascularization for a lesion treated by a membrane-covered device. The mean
      minimal luminal diameter of lesions covered by a conventional stent decreased by
      42% to 1.4 +/- 0.6 mm; the mean minimal luminal diameter of the lesions treated
      by a stent graft declined by 9% to 2.8 +/- 0.6 mm (P < 0.05). This series of
      intraindividual comparisons suggests that membrane-covered stents may have the
      power to reduce in-stent restenosis in obstructed aortocoronary venous bypass
      grafts.

PMID- 11329209
TI  - If it can keep eggs off the frying pan....

PMID- 11329210
TI  - Impact of contrast agent type (ionic versus nonionic) used for coronary
      angiography on angiographic, electrocardiographic, and clinical outcomes
      following thrombolytic administration in acute myocardial infarction.
AB  - The goal of this study was to examine the relationship between contrast agent
      type (ionic vs. nonionic) and angiographic, electrocardiographic, and clinical
      outcomes after thrombolytic administration. Ionic or nonionic contrast agents
      were selected in a nonrandomized fashion for 90-min angiography and percutaneous
      coronary intervention (PCI) following thrombolytic administration in the TIMI 14
      trial [tissue plasminogen activator (tPA) or reteplase (rPA) vs. low-dose lytic +
      abciximab]. There was no relationship between contrast agent type and overall
      patency, rate of TIMI grade 3 flow, or corrected TIMI frame counts (CTFCs) in
      open culprit arteries and in post-PCI patency rates or post-PCI CTFCs. In
      patients treated with ionic contrast, ejection fractions at 90 min were slightly
      but significantly lower (56.2 +/- 16.5, n = 122, vs. 59.8 +/- 14.4, n = 322; P =
      0.02), chest pain duration was longer (2.8 +/- 4.1 hr, n = 255, vs. 1.7 +/- 3.6,
      n = 550; P = 0.0003), and complete ST segment resolution was less frequent (41.5%
      vs. 50.8%; P = 0.04). While there was no difference in epicardial blood flow,
      ionic contrast agent use was associated with poorer ST segment resolution, longer
      chest pain duration, and poorer ejection fractions, perhaps as a result of
      microvascular dysfunction.

PMID- 11329211
TI  - Directional atherectomy prior to stenting in bifurcation lesions: a matched
      comparison study with stenting alone.
AB  - The ideal catheter-based intervention for treatment of coronary lesions at
      bifurcation site still has to be defined. The aim of the study was to assess the
      acute and long-term outcome after treatment of bifurcation lesions with
      directional atherectomy (DCA) and stenting in comparison with stenting alone.
      Thirty-one consecutive patients treated for bifurcation coronary lesions (62
      lesions) with DCA and stenting in at least one branch (DCA group) were compared
      with a matched group of 31 patients with bifurcation coronary lesions (62
      lesions) treated with stenting alone in at least one branch (non-DCA group).
      Procedural success was 87.1% in the DCA group compared with 100% in the non-DCA
      group (P = 0.03). In-hospital major adverse cardiac events (MACE) occurred only
      in the DCA group (12.9% vs. 0%, P = 0.03), mainly non-Q-wave myocardial
      infarction. After the procedure, minimum lumen diameter (MLD) and acute gain were
      significantly greater (P = 0.004 and P = 0.05, respectively) and % diameter
      stenosis was significantly lower (P = 0.05) in the main branch in the DCA group.
      At follow-up angiogram, MLD in the main branch was still significantly greater in
      the DCA group compared to the non-DCA group (2.31 vs. 1.65, respectively, P =
      0.04), with no significant difference in late loss and loss index between the two
      groups. Restenosis rate was 28.8% in the DCA group vs. 43.5% in the non-DCA group
      (P = 0.13). The incidence of follow-up MACE was 29% in the DCA group compared
      with 48.4% in the non-DCA group, mainly due to target lesion revascularization.
      In conclusion, treatment of bifurcation coronary lesions with DCA and stenting
      was associated with greater acute gain after the procedure and greater MLD at
      follow-up in the main branch compared with stenting alone. Procedural myocardial
      infarction was more frequent in the DCA group. Restenosis rates and follow-up
      MACE were lower following DCA and stenting, without reaching any statistical
      significance.

PMID- 11329212
TI  - Atherectomy prior to stenting bifurcation lesions: fork in the road, which
      direction do we choose?

PMID- 11329213
TI  - Late stent thrombosis in the absence of prior intracoronary brachytherapy.
AB  - Late stent thrombosis has not been reported in the absence of prior coronary
      brachytherapy. We reviewed our experience in 1,855 consecutive patients who
      received at least one stent and did not receive coronary brachytherapy. Half of
      all stent thromboses occurred within the first week and nearly 65% (22) occurred
      within 15 days. The incidence of stent thrombosis within this traditional time
      frame was 1.2%. An additional 12 patients, however, presented with stent
      thrombosis between 33 and 270 days post-procedure (mean = 72.9 +/- 23 days). The
      true incidence of stent thrombosis was therefore 1.8% (34/1,855). There were
      three bypass operations, one stroke and two deaths in the late stent thrombosis
      group. Late stent thrombosis is an unusual but serious complication in patients
      who have not received coronary brachytherapy. Intracoronary radiation may
      potentiate a phenomenon that already occurs after stent deployment. Prolonged
      treatment (6-12 months) with anti-platelet agents should be considered after
      percutaneous intervention with coronary stents.

PMID- 11329214
TI  - Agreement between coronary flow velocity reserve and stress echocardiography in
      intermediate-severity coronary stenoses.
AB  - Visual and quantitative assessments of percent diameter stenosis on coronary
      angiography correlate poorly with functional testing, particularly in
      intermediate-severity (40%-70%) lesions, yet are frequently relied on to make
      decisions regarding revascularization. Coronary flow velocity reserve (CFVR) and
      relative CFVR (RCFVR) are promising methods for on-line functional assessment of
      lesion severity in the catheterization laboratory. We sought to determine the
      agreement between maximal, mean, and relative CFVR and stress echocardiography in
      intermediate-severity stenoses. The results of exercise or dobutamine stress
      echocardiography and CFVR measured by intracoronary Doppler were compared in 28
      patients referred for assessment of intermediate-severity stenoses, using 15
      patients with either angiographically normal coronary arteries or diameter
      stenoses > 70% as reference groups. CFVR was measured at least three times in
      response to a bolus of adenosine in the target vessel distal to the stenosis.
      RCFVR (target/normal vessel CFVR) was also measured in 27 patients. Maximal, mean
      (of three measures), and relative CFVR were calculated. CFVR > or = 2.0 and RCFVR
      > or = 0.75 were accepted as normal. A minority (29%) of patients in the
      intermediate-severity stenosis group had a positive test by either method. There
      was good to very good agreement between stress echocardiography and maximal CFVR
      (84%, kappa = 0.62, P < 0.0001) and RCFVR (81%, kappa = 0.59, P < 0.001) across
      the entire patient cohort, though in the intermediate subgroup concordance was
      only fair. Using the mean (of three measures of) CFVR for the same comparison
      improved the agreement in the intermediate subgroup to good (86%, kappa = 0.58, P
      = 0.002), and in the entire cohort the agreement was very good (88%, kappa =
      0.74, P < 0.0001). There was only fair correlation between measures of CFVR and
      percent coronary stenosis. CFVR improved from 1.8 +/- 0.8 to 2.7 +/- 0.7 after
      percutaneous intervention (n = 12, P < 0.0001). These results suggest that there
      is good agreement between CFVR and stress echocardiography across a wide range of
      coronary lesion severity. The mean of three CFVR measurements distal to the
      target vessel stenosis increases diagnostic accuracy. Intracoronary Doppler flow
      velocity measurements at the time of cardiac catheterization may facilitate
      improved decision-making by providing the ability to assess the functional
      significance of coronary stenoses on-line.

PMID- 11329215
TI  - If invasive functional testing is so great, why aren't we doing it routinely?

PMID- 11329216
TI  - Trends in cardiac catheterization laboratories in the United States.
AB  - The Society for Cardiac Angiography and Interventions has periodically published
      a Directory of Cardiac Catheterization Laboratories in the United States. All
      known catheterization laboratories are surveyed and certain operational
      characteristics are queried. These surveys, in 1983, 1987, 1993, 1995 and 1998,
      have demonstrated a 2.5 fold increase in cardiac catheterization laboratories
      since 1983, corresponding increases in numbers of physicians that perform
      procedures, and in the numbers of procedures performed, reflecting advances in
      cardiovascular medicine and technology. These surveys have also documented the
      evolution of interventional techniques, and a shift away from film based imaging,
      to digitally based methods. These data provide a substrate for consideration of
      national cardiovascular objectives and planning of future resource allocation by
      cardiovascular physicians and their colleagues.

PMID- 11329217
TI  - Cardiac catheterization laboratories: do they have a future in diagnosis.

PMID- 11329218
TI  - Prediction of the physiologic severity of coronary lesions using 3D IVUS:
      validation by direct coronary pressure measurements.
AB  - This study was performed to determine whether three-dimensional intravascular
      ultrasound (3D IVUS) could predict the physiologic significance of coronary
      lesions. Seventeen lesions were evaluated by means of 3D IVUS, pressure
      measurements, and quantitative coronary angiography. Physiologic parameters were
      calculated from the 3D IVUS measures using established equations and compared to
      values measured by pressure guidewire. IVUS minimum lumen area (MLA) correlated
      with fractional flow reserve (FFR; R2 = 0.55, P = 0.003) and pressure gradient
      (R2 = 0.52, P = 0.003). Lesion length (L) had a positive correlation with
      pressure gradient (R2 = 0.45, P = 0.007). By multivariate analysis, the only
      significant independent determinant of FFR was MLA/L measured by IVUS. The IVUS
      predicted pressure gradient and FFR were well correlated with values measured
      directly (R2) = 0.88, P < 0.001; R2 = 0.90, P < 0.001, respectively). The
      physiologic severity of coronary lesions is primarily influenced by lumen area
      and lesion length and can be established by 3D IVUS.

PMID- 11329219
TI  - Atherosclerosis and plaque rupture.

PMID- 11329220
TI  - Use of fractional flow reserve in the treatment of a calcific bifurcation left
      anterior descending coronary stenosis with rotational atherectomy.
AB  - We report the results of an intervention in a high-risk surgical patient
      undergoing rotational atherectomy in a bifurcating lesion. The use of fractional
      flow reserve (FFR) was especially helpful due to the inability to visualize
      clearly the angiographic anatomy both before and following intervention.

PMID- 11329221
TI  - Combined percutaneous pulmonary valvuloplasty and atrial septal defect closure
      for pulmonary valvular stenosis and associated secundum atrial septal defect in
      an adult.
AB  - Percutaneous balloon valvuloplasty is the treatment of choice for congenital
      pulmonary valve stenosis, and percutaneous closure of secundum atrial septal
      defects has become a promising alternative to surgery in selected patients. We
      report a case of combined percutaneous pulmonary valvuloplasty and secundum
      atrial septal defect occlusion in an adult patient.

PMID- 11329222
TI  - Laser angioplasty in a right coronary artery stent restenosis with the guidance
      of left internal mammary artery contrast injection: case report.
AB  - A 43-years-old male who underwent right coronary artery stent implantation 6
      months ago presented with total occlusion of right coronary artery at proximal
      part of the stent without antegrade flow. We successfully used the left internal
      mammary artery contrast injections for guidance in all stages of the right
      coronary laser angioplasty intervention.

PMID- 11329223
TI  - Ductal stents in the management of congenital heart defects.

PMID- 11329224
TI  - Transcatheter recanalization of the left main pulmonary artery after four years
      of complete occlusion.
AB  - A technique for transcatheter "reconstruction" of a completely occluded left
      pulmonary artery using radiofrequency perforation with subsequent balloon
      dilation and stent implantation is reported in a 7-year-old child. It is shown
      that transcatheter radiofrequency perforation can still be effective years after
      the occlusion of a vessel.

PMID- 11329225
TI  - Evaluation of diastolic function.
AB  - Abnormalities of diastolic function are increasingly recognized as important
      components of the abnormal physiology in many patients with heart failure. In
      order to better understand the role of abnormalities of individual parameters or
      diastolic function affecting filling of the left ventricular a broader
      understanding of the relationship of systolic and diastolic performance on
      overall left ventricular pump performance should be considered. While measurement
      of diastolic function noninvasively has become the predominant way of assessing
      diastolic performance, invasive evaluation remains important. Moreover,
      understanding the physiology of diastolic performance remains essential to proper
      diagnosis and management.

PMID- 11329226
TI  - Pitfalls of atrial septal defect sizing using meditech sizing balloon.

PMID- 11329228
TI  - Proceedings of the 6th International Colloquium on Paratuberculosis. Melbourne,
      Australia, 14-18 February 1999.

PMID- 11329230
TI  - Avoidance of hypoglycemia restores hypoglycemia awareness by increasing beta
      adrenergic sensitivity in type 1 diabetes.
AB  - BACKGROUND: Lack of awareness of hypoglycemia is a major limiting factor in the
      management of type 1 diabetes. OBJECTIVE: To examine whether reduction in the
      number of episodes of hypoglycemia restores hypoglycemia awareness by influencing
      beta-adrenergic sensitivity in patients with type 1 diabetes. DESIGN: Controlled
      interventional study. SETTING: Research unit and outpatient diabetes clinic of a
      university hospital. PATIENTS: 10 men with type 1 diabetes and hypoglycemia
      unawareness (mean age [+/-SD], 46 +/- 16 years; mean duration of diabetes, 20 +/-
      10 years). INTERVENTION: Strict avoidance of hypoglycemia. MEASUREMENTS: beta
      Adrenergic sensitivity was measured by isoproterenol testing before and at 2 and
      4 months after strict avoidance of hypoglycemia. Hypoglycemia awareness and
      catecholamine response were measured by performing hypoglycemic clamp (glucose
      level, 3 mmol/L [54 mg/dL]) before and after 4 months of avoidance of
      hypoglycemia. RESULTS: After 4 months, the mean (+/-SE) number of episodes of
      hypoglycemia (glucose level < 3.9 mmol/L [70 mg/dL]) decreased from 8.4 +/- 0.9
      to 1.4 +/- 0.3 per week (P < 0.001). Hemoglobin A(1c) values increased from 0.068
      +/- 0.003 (6.8% +/- 0.3%) to 0.077 +/- 0.003 (7.7% +/- 0.3%) (P < 0.001).
      Autonomic symptom scores during hypoglycemic clamp increased from 1.8 +/- 0.6 to
      3.3 +/- 0.7 (P = 0.004) and did not significantly differ from those of normal
      participants (4.7 +/- 0.8) (P > 0.2). Although catecholamine responses to
      hypoglycemia were unchanged, the dose of isoproterenol necessary to increase
      heart rate by 25 beats/min (IC(25)) decreased from 1.96 +/- 0.43 microgram before
      treatment to 1.09 +/- 0.17 microgram after 4 months of treatment (P = 0.01), a
      value similar to that in normal participants (0.85 +/- 0.20 microgram) (P > 0.2).
      Improvements in beta-adrenergic sensitivity (change in IC(25)(-1)) were
      correlated with improvements in autonomic symptoms (r = 0.65; P = 0.04).
      CONCLUSIONS: Avoidance of hypoglycemia in patients with type 1 diabetes who have
      hypoglycemia unawareness seems to restore hypoglycemia awareness, primarily by
      increasing beta-adrenergic sensitivity.

PMID- 11329229
TI  - Maternally inherited diabetes and deafness: a multicenter study.
AB  - BACKGROUND: Maternally inherited diabetes and deafness (MIDD), which is seen in
      0.5% to 2.8% of patients with type 2 diabetes mellitus, is related to a point
      mutation at position 3243 of mitochondrial (mt) DNA. Its clinical description is
      incomplete. OBJECTIVE: To study the clinical presentation and complications of
      diabetes in patients with MIDD and to identify clinical characteristics that may
      help select diabetic patients for mtDNA mutation screening. DESIGN: Multicenter
      prospective descriptive study. SETTING: 16 French departments of internal
      medicine, diabetes and metabolic diseases, or both. PATIENTS: 54 patients with
      type 2 diabetes mellitus and the mtDNA 3243 mutation. MEASUREMENTS:
      Characteristics of diabetes, metabolic control (glycosylated hemoglobin level),
      complications of diabetes, and involvement of other organs. RESULTS: On average,
      patients with MIDD were young at diabetes onset and presented with a normal or
      low body mass index. None were obese. Seventy-three percent of probands had a
      maternal family history of diabetes. Diabetes was non-insulin-dependent at onset
      in 87% of patients; however, 46% of patients had non-insulin-dependent disease at
      onset but progressed to insulin therapy after a mean duration of approximately 10
      years. Neurosensory hearing loss was present in almost all patients. Eighty-six
      percent of patients who received an ophthalmologic examination had macular
      pattern dystrophy (a specific retinal lesion). Forty-three percent of patients
      had myopathy, 15% had cardiomyopathy, and 18% (9 of 51) had neuropsychiatric
      symptoms. Although the prevalence of diabetic retinopathy was 8% among patients
      who received an ophthalmologic examination, lower than expected after a mean 12
      year duration of diabetes, prevalence of kidney disease was 28%. This suggests
      that a specific renal involvement was the result of mitochondrial disease.
      CONCLUSIONS: Maternally inherited diabetes and deafness has a specific clinical
      profile that may help identify diabetic patients for mtDNA testing.

PMID- 11329231
TI  - The effect of a thiazolidinedione drug, troglitazone, on glycemia in patients
      with type 2 diabetes mellitus poorly controlled with sulfonylurea and metformin.
      A multicenter, randomized, double-blind, placebo-controlled trial.
AB  - BACKGROUND: The thiazolidinediones are a new class of antidiabetes medication
      that enhances the actions of insulin in muscle, liver, and adipose tissue. Data
      have been lacking on their use in combination with both sulfonylurea and
      metformin among patients for whom insulin is the usual therapeutic alternative
      for improved glycemic control. OBJECTIVE: To determine the effects of
      troglitazone on hemoglobin A(1c) level in patients treated with maximum tolerated
      doses of sulfonylurea and metformin who have hemoglobin A(1c) levels of at least
      0.085 (8.5%). This trial was completed before troglitazone was taken off the U.S.
      market. DESIGN: Randomized, double-blind, placebo-controlled trial, followed by
      an open-label extension during which all patients received troglitazone. SETTING:
      16 outpatient clinics in Canada. PATIENTS: 200 patients (mean age, 59 years) with
      type 2 diabetes mellitus and hemoglobin A(1c) levels at least 0.085 (8.5%) (mean
      hemoglobin A(1c) level, 0.097 [9.7%] and mean fasting plasma glucose level, 12.9
      mmol/L [233 mg/dL]) while receiving maximum doses of sulfonylurea and metformin.
      MEASUREMENTS: Levels of hemoglobin A(1c), fasting plasma glucose, total insulin,
      triglycerides, total cholesterol, low-density lipoprotein cholesterol, and high
      density lipoprotein cholesterol. RESULTS: Troglitazone, 400 mg/d, when added to
      sulfonylurea and metformin, significantly decreased hemoglobin A(1c) level by
      0.014 +/- 0.002 (95% CI, 0.0167 to 0.0109; P < 0.001) (1.4% +/- 0.2% [CI, 1.67%
      to 1.09%]) and insulin by 19 +/- 4 pmol/L (CI, 30 to 10 pmol/L; P < 0.001). At 6
      months, 43% of troglitazone-treated patients achieved hemoglobin A(1c) levels of
      0.08 (8%) or lower compared with 6% of placebo recipients. Efficacy was
      maintained at 12 months. CONCLUSIONS: The thiazolidinedione troglitazone, at a
      dosage of 400 mg/d, is effective when used in combination with sulfonylurea and
      metformin. Thiazolidinediones may therefore offer an effective alternative to
      insulin for patients treated with sulfonylurea and metformin who do not achieve
      adequate glycemic control.

PMID- 11329232
TI  - Effect of dose-intensive intravenous melphalan and autologous blood stem-cell
      transplantation on al amyloidosis-associated renal disease.
AB  - BACKGROUND: Dose-intensive intravenous melphalan with autologous blood stem-cell
      transplantation induces remission of the plasma cell dyscrasia in a substantial
      proportion of patients with AL amyloidosis. The impact of this treatment on
      associated renal disease is not known. OBJECTIVE: To determine the effect of dose
      intensive intravenous melphalan and autologous blood stem-cell transplantation on
      AL amyloidosis-associated renal disease. DESIGN: Prospective cohort study.
      SETTING: Academic medical center. PATIENTS: 65 patients with AL amyloidosis and
      urinary protein excretion greater than 1 g/24 h who received dose-intensive
      intravenous melphalan and autologous blood stem-cell transplantation between 1
      July 1994 and 30 June 1998. MEASUREMENTS: 24-hour urinary protein excretion,
      serum cholesterol level, serum albumin level, creatinine clearance, urine and
      serum immunoelectrophoresis, and bone marrow biopsy. Renal response was defined
      as a greater than 50% reduction in urinary protein excretion in the absence of a
      25% or greater reduction in creatinine clearance. Complete hematologic response
      was defined as absence of detectable monoclonal protein in serum and urine and a
      bone marrow specimen containing less than 5% plasma cells without clonal
      dominance of kappa or lambda isotype. RESULTS: Among the 50 patients who survived
      for at least 12 months, proteinuria, hypoalbuminemia, and hypercholesterolemia
      improved during follow-up; 36% met criteria for a renal response. Median 24-hour
      urinary protein excretion decreased from a baseline value of 9.6 g/24 h to 1.6
      g/24 h at 12 months among patients with complete hematologic response, and 71%
      met criteria for a renal response. Twenty-hour urinary protein excretion did not
      decrease during follow-up among patients with persistent plasma cell disease, and
      only 11% had a renal response at 12 months (P < 0.001 for hematologic responders
      vs. nonresponders). CONCLUSION: Dose-intensive intravenous melphalan with
      autologous blood stem-cell transplantation improves the nephrotic syndrome in
      patients with AL amyloidosis-associated renal disease. The benefit is largely
      limited to patients achieving eradication of the underlying plasma cell
      dyscrasia.

PMID- 11329233
TI  - Effects of hormone replacement therapy on serum lipids in elderly women. a
      randomized, placebo-controlled trial.
AB  - BACKGROUND: Coronary heart disease (CHD) is the leading cause of death among
      older women. In observational studies, the incidence of CHD has been reduced in
      postmenopausal women who take hormone replacement therapy (HRT). A low serum
      level of high-density lipoprotein (HDL) cholesterol is one of the risk factors
      predictive of death from CHD. OBJECTIVE: To determine the effects of HRT on serum
      lipid and lipoprotein levels in elderly women. DESIGN: Randomized, double-blind,
      placebo-controlled trial. SETTING: University research center. PARTICIPANTS: 59
      sedentary women 75 years of age or older. INTERVENTION: Participants were
      assigned to 9 months of oral therapy with placebo or conjugated estrogens, 0.625
      mg/d, plus trimonthly medroxyprogesterone acetate, 5 mg/d for 13 days.
      MEASUREMENTS: Serum lipid and lipoprotein levels. RESULTS: After 9 months of
      treatment, women in the HRT group compared with women in the placebo group had
      decreased low-density lipoprotein cholesterol levels (mean change [+/-SD], -0.47
      +/- 0.69 mmol/L [-18.2 +/- 26.5 mg/dL] vs. -0.06 +/- 0.32 mmol/L [-2.2 +/- 12.2
      mg/dL], respectively; between-group difference, 0.41 mmol/L [95% CI, 0.09 to 0.74
      mmol/L], 16 mg/dL [95% CI, 3.5 to 28.5 mg/dL]; P = 0.01) and increased HDL
      cholesterol levels (mean change, 0.21 +/- 0.27 mmol/L [8.1 +/- 10.5 mg/dL] vs.
      0.06 +/- 0.11 mmol/L [2.4 +/- 4.3 mg/dL], respectively; between-group difference,
      0.15 mmol/L [CI, 0.008 to 0.29 mmol/L], 5.7 mg/dL [CI, 0.8 to 10.6 mg/dL]; P =
      0.02). The observed changes were independent of age at menopause onset, baseline
      lipid values, body weight, waist circumference, percentage body fat, and peak
      aerobic power. CONCLUSIONS: In women 75 years of age or older, HRT improved the
      lipoprotein profile to the extent observed previously in younger postmenopausal
      women. Further studies are needed to evaluate whether these effects protect
      against CHD in this population.

PMID- 11329234
TI  - Host determinants in HIV infection and disease. Part 1: cellular and humoral
      immune responses.
AB  - The course of HIV infection varies widely among individuals. Long-term
      nonprogressors or slow progressors may remain asymptomatic and have normal CD4
      counts despite more than a decade of untreated HIV infection. In contrast, rapid
      progressors develop AIDS within 5 years. In addition, some persons remain
      uninfected despite repeated exposure to HIV. Immunologic and genetic studies of
      long-term nonprogressors and exposed yet uninfected persons, as well as data from
      studies of primary HIV infection, have helped to elucidate the mechanisms by
      which some persons are protected from HIV acquisition or have slow rates of
      disease progression. This review (the first of two parts) describes what is
      currently known about host factors in HIV-1 infection. Studies for inclusion were
      identified by a systematic search of PubMed for English-language literature
      published from 1988 through June 2000. Abstracts of presentations at major
      meetings convened in 2000 were also included if appropriate. Growing evidence
      suggests a crucial role of cytotoxic T cells and T-helper cells in controlling
      viremia, slowing disease progression, and perhaps preventing establishment of
      infection. Humoral and mucosal immunity, soluble inhibitory factors, the cytokine
      milieu, and concomitant infections also affect outcome. Genetic host factors,
      such as inheritance of mutant chemokine receptors or certain HLA types, affect
      susceptibility to infection and subsequent clinical course. The role of cellular
      and humoral immunity, mucosal immunity, and other local factors in determining
      the course of HIV infection is discussed.

PMID- 11329235
TI  - Mitochondrial DNA mutations and diabetes: another step toward individualized
      medicine.

PMID- 11329236
TI  - Can joint negotiation restore physicians' professional autonomy?

PMID- 11329237
TI  - Symptoms: in the head or in the brain?

PMID- 11329239
TI  - Physicians and joint negotiations.
AB  - This position paper of the American College of Physicians-American Society of
      Internal Medicine addresses public policy issues related to physicians' joining
      to negotiate issues affecting patient care and the working environment in which
      patient services are provided. It seeks to identify an appropriate way for
      physicians to negotiate jointly with health care plans while maintaining
      professionalism and keeping the interests of patients paramount. It proposes that
      physicians in nonintegrated private practices should be able to meet and
      communicate among themselves for the purpose of negotiating primarily with health
      care plans about specific issues that affect quality and access. However, the
      College opposes strikes or any joint action by physicians that would deny or
      limit services to patients or result in price-fixing or other anticompetitive
      behavior. The College states that employed physicians should continue to have
      negotiating rights. It maintains, despite a recent decision by the National Labor
      Relations Board, that physicians in residency training are protected by
      accreditation requirements for programs of graduate medical education, and
      education content should not be subject to negotiations [corrected]. Physicians
      in residency training are protected by accreditation requirements for programs of
      graduate medical education, and educational content should not be subject to
      negotiations. The College also calls for determination of negotiating units for
      physicians but recommends that nonphysician providers not be included in the same
      units as physicians. Membership in an organization that negotiates for physicians
      should be voluntary, and conflict-resolution mechanisms must be available for
      resolving impasses.

PMID- 11329240
TI  - On being a doctor. Mrs. Posner's smile.

PMID- 11329241
TI  - Inhaled insulin: a proof-of-concept study.

PMID- 11329242
TI  - Body size and vertebral fractures.

PMID- 11329244
TI  - Airway adrenaline in patients with severe cardiac disease.

PMID- 11329246
TI  - Salary equity among male and female internists.

PMID- 11329248
TI  - Isoniazid-induced beta-hydroxybutyric acidosis.

PMID- 11329252
TI  - Reaction-induced infrared difference spectroscopy for the study of protein
      reaction mechanisms.
AB  - This paper reviews state-of-the-art reaction-induced infrared difference
      spectroscopy of proteins. This technique enables detailed characterization of
      enzyme function on the level of single bonds of proteins, cofactors, or
      substrates. The following methods to initiate a reaction in the infrared sample
      are discussed: (i) light-induced difference spectroscopy, (ii) attenuated total
      reflection with buffer exchange, (iii) the infrared variant of stopped and
      continuous flow, (iv) temperature and pressure jump, (v) photolytical release of
      effector substances from caged compounds, (vi) equilibrium electrochemistry, and
      (vii) photoreduction. Illustrating applications are given including hot topics
      from the fields of bioenergetics, protein folding, and molecule--protein
      interaction.

PMID- 11329253
TI  - Structure of the metal-water complex in Ras x GDP studied by high-field EPR
      spectroscopy and 31P NMR spectroscopy.
AB  - The small GTPase Ras plays a key role as a molecular switch in the intercellular
      signal transduction. On Mg(2+) --> Mn(2+) substituted samples, the first ligand
      sphere of the metal ion in the inactive, GDP-bound Ras has been studied by
      continuous wave EPR at 94 GHz (W-band). Via replacement of normal water with
      (17)O-enriched water, the (17)O--(55)Mn superhyperfine coupling was used to
      determine the number of water ligands bound to the metal ion. In contrast to EPR
      data on frozen solutions and X-ray data from single crystals where four direct
      ligands to the metal ion are found, the wild-type protein has only three water
      ligands bound in solution at room temperature. The same number of water ligands
      is found for the mutant Ras(T35S). However, for the alanine mutant in position 35
      Ras(T35A) as well as for the oncogenic mutant Ras(G12V), four water ligands can
      be observed in liquid solution. The EPR studies were supplemented by (31)P NMR
      studies on the Mg(2+) x GDP complexes of the wild-type protein and the three
      mutants. Ras(T35A) exists in two conformational states (1 and 2) with an
      equilibrium constant K(1)(1,2) of approximately 0.49 and rate constants k(1--1)
      which are much smaller than 40 s(-1) at 298 K. For wild-type Ras and Ras(T35S),
      the two states can also be observed with equilibrium constants K(1)(1,2) of
      approximately 0.31 and 0.21, respectively. In Ras(G12V), only one conformational
      state could be detected.

PMID- 11329254
TI  - Structural Insights into the A1 ATPase from the archaeon, Methanosarcina mazei
      Go1.
AB  - The low-resolution structure and overall dimensions of the A(3)B(3)CDF complex of
      the A(1) ATPase from Methanosarcina mazei Go1 in solution is analyzed by
      synchrotron X-ray small-angle scattering. The radius of gyration and the maximum
      size of the complex are 5.03 +/- 0.1 and 18.0 +/- 0.1 nm, respectively. The low
      resolution shape of the protein determined by two independent ab initio
      approaches has a knob-and-stalk-like feature. Its headpiece is approximately 9.4
      nm long and 9.2 nm wide. The stalk, which is known to connect the headpiece to
      its membrane-bound A(O) part, is approximately 8.4 nm long. Limited tryptic
      digestion of the A(3)B(3)CDF complex was used to probe the topology of the
      smaller subunits (C-F). Trypsin was found to cleave subunit C most rapidly at
      three sites, Lys(20), Lys(21), and Arg(209), followed by subunit F. In the
      A(3)B(3)CDF complex, subunit D remained protected from proteolysis.

PMID- 11329255
TI  - Human thymidylate synthase is in the closed conformation when complexed with dUMP
      and raltitrexed, an antifolate drug.
AB  - Thymidylate synthase (TS) is a major target in the chemotherapy of colorectal
      cancer and some other neoplasms while raltitrexed (Tomudex, ZD1694) is an
      antifolate inhibitor of TS approved for clinical use in several European
      countries. The crystal structure of the complex between recombinant human TS,
      dUMP, and raltitrexed has been determined at 1.9 A resolution. In contrast to the
      situation observed in the analogous complex of the rat TS, the enzyme is in the
      closed conformation and a covalent bond between the catalytic Cys 195 and dUMP is
      present in both subunits. This mode of ligand binding is similar to that of the
      analogous complex of the Escherichia coli enzyme. The only major differences
      observed are a direct hydrogen bond between His 196 and the O4 atom of dUMP and
      repositioning of the side chain of Tyr 94 by about 2 A. The thiophene ring of the
      drug is disordered between two parallel positions.

PMID- 11329256
TI  - The crystal structure of phosphinothricin in the active site of glutamine
      synthetase illuminates the mechanism of enzymatic inhibition.
AB  - Phosphinothricin is a potent inhibitor of the enzyme glutamine synthetase (GS).
      The resolution of the native structure of GS from Salmonella typhimurium has been
      extended to 2.5 A resolution, and the improved model is used to determine the
      structure of phosphinothricin complexed to GS by difference Fourier methods. The
      structure suggests a noncovalent, dead-end mechanism of inhibition.
      Phosphinothricin occupies the glutamate substrate pocket and stabilizes the
      Glu327 flap in a position which blocks the glutamate entrance to the active site,
      trapping the inhibitor on the enzyme. One oxygen of the phosphinyl group of
      phosphinothricin appears to be protonated, because of its proximity to the
      carboxylate group of Glu327. The other phosphinyl oxygen protrudes into the
      negatively charged binding pocket for the substrate ammonium, disrupting that
      pocket. The distribution of charges in the glutamate binding pocket is
      complementary to those of phosphinothricin. The presence of a second ammonium
      binding site within the active site is confirmed by its analogue thallous ion,
      marking the ammonium site and its protein ligands. The inhibition of GS by
      methionine sulfoximine can be explained by the same mechanism. These models of
      inhibited GS further illuminate its catalytic mechanism.

PMID- 11329257
TI  - Structure of the Escherichia coli GlmU pyrophosphorylase and acetyltransferase
      active sites.
AB  - N-Acetylglucosamine-1-PO(4) uridyltransferase (GlmU) is a trimeric bifunctional
      enzyme that catalyzes the last two sequential reactions in the de novo
      biosynthetic pathway for UDP-GlcNAc. The X-ray crystal structure of Escherichia
      coli GlmU in complex with UDP-GlcNAc and CoA has been determined to 2.1 A
      resolution and reveals a two-domain architecture that is responsible for these
      two reactions. The C-terminal domain is responsible for the CoA-dependent
      acetylation of Glc-1-PO(4) to GlcNAc-1-PO(4) and displays the longest left-handed
      parallel beta-helix observed to date. The acetyltransferase active site defined
      by the binding site for CoA makes use of residues from all three subunits and is
      positioned beneath an open cavity large enough to accommodate the Glc-1-PO(4)
      acetyl acceptor. The N-terminal domain catalyzes uridyl transfer from UTP to
      GlcNAc-1-PO(4) to form the final products UDP-GlcNAc and pyrophosphate. This
      domain is composed of a central seven-stranded beta-sheet surrounded by six alpha
      helices in a Rossmann fold-like topology. A Co(2+) ion binds to just one of the
      two independent pyrophosphorylase active sites present in the crystals studied
      here, each of which nonetheless binds UDP-GlcNAc. The conformational changes of
      the enzyme and sugar nucleotide that accompany metal binding may provide a window
      into the structural dynamics that accompany catalysis.

PMID- 11329258
TI  - Conformational changes in the nucleosome followed by the selective accessibility
      of histone glutamines in the transglutaminase reaction: effects of ionic
      strength.
AB  - Transglutaminases, the enzymes that catalyze the acyl-transfer reaction between
      glutamine and primary amines, have been used to introduce probes into proteins in
      order to perform structural studies using physical techniques. Here we use an
      original approach in which the increasing accessibility of the glutamines of core
      histones to TGase is used to monitor the salt-induced conformational changes of
      the nucleosome. The rationale of this strategy is that the accessibility of a
      glutamine to transglutaminase depends on the blockage due to the presence of
      either other histones or DNA. At low ionic strength, only glutamines on the N
      terminal tails of H2B and H3 are labeled with monodansylcadaverine when core
      particles are incubated with transglutaminase. The partial unfolding that occurs
      when going to higher ionic strength values results in an increase in the number
      of reactive glutamines up to a maximum value of 16 per nucleosome. Labeling of
      some residues (e.g., Gln(104) and Gln(112) of H2A) requires the unwinding of DNA
      and the dissociation of the H2A--H2B dimers. Gln(76) of H3 is labeled in the H3-
      H4 tetramer only when the H2A--H2B dimers are dissociated. Interestingly, the
      labeling of Gln(95) of H2B exclusively depends on the unwinding of DNA. The
      accurate analysis of these results indicates that the ionic-dependent unwinding
      of the DNA may occur following a two-state model.

PMID- 11329259
TI  - Covariation of a specificity-determining structural motif in an aminoacyl-tRNA
      synthetase and a tRNA identity element.
AB  - Transfer RNA (tRNA) identity determinants help preserve the specificity of
      aminoacylation in vivo, and prevent cross-species interactions. Here, we
      investigate covariation between the discriminator base (N73) element in histidine
      tRNAs and residues in the histidyl-tRNA synthetase (HisRS) motif 2 loop. A model
      of the Escherichia coli HisRS--tRNA(His) complex predicts an interaction between
      the prokaryotic conserved glutamine 118 of the motif 2 loop and cytosine 73. The
      substitution of Gln 118 in motif 2 with glutamate decreased discrimination
      between cytosine and uracil some 50-fold, but left overall rates of adenylation
      and aminoacylation unaffected. By contrast, substitutions at neighboring Glu 115
      and Arg 121 affected both adenylation and aminoacylation, consistent with their
      predicted involvement in both half-reactions. Additional evidence for the
      involvement of the motif 2 loop was provided by functional analysis of a hybrid
      Saccharomyces cerevisiae-- E. coli HisRS possessing the 11 amino acid motif 2
      loop of the yeast enzyme. Despite an overall decreased activity of nearly 1000
      fold relative to the E. coli enzyme, the chimera nevertheless exhibited a modest
      preference for the yeast tRNA(His) over the E. coli tRNA, and preferred wild-type
      yeast tRNA(His) to a variant with C at the discriminator position. These
      experiments suggest that part of, but not all of, the specificity is provided by
      the motif 2 loop. The close interaction between enzyme loop and RNA sequence
      elements suggested by these experiments reflects a covariation between enzyme and
      tRNA that may have acted to preserve aminoacylation fidelity over evolutionary
      time.

PMID- 11329260
TI  - Identification of human CYP2C19 residues that confer S-mephenytoin 4'
      hydroxylation activity to CYP2C9.
AB  - CYP2C19 is selective for the 4'-hydroxylation of S-mephenytoin while the highly
      similar CYP2C9 has little activity toward this substrate. To identify critical
      amino acids determining the specificity of human CYP2C19 for S-mephenytoin 4'
      hydroxylation, we constructed chimeras by replacing portions of CYP2C9 containing
      various proposed substrate recognition sites (SRSs) with those of CYP2C19 and
      mutating individual residues by site-directed mutagenesis. Only a chimera
      containing regions encompassing SRSs 1--4 was active (30% of wild-type CYP2C19),
      indicating that multiple regions are necessary to confer specificity for S
      mephenytoin. Mutagenesis studies identified six residues in three topological
      components of the proteins required to convert CYP2C9 to an S-mephenytoin 4'
      hydroxylase (6% of the activity of wild-type CYP2C19). Of these, only the I99H
      difference located in SRS 1 between helices B and C reflects a change in a side
      chain that is predicted to be in the substrate-binding cavity formed above the
      heme prosthetic group. Two additional substitutions, S220P and P221T residing
      between helices F and G but not in close proximity to the substrate binding site
      together with five differences in the N-terminal portion of helix I conferred S
      mephenytoin 4'-hydroxylation activity with a K(M) similar to that of CYP2C19 but
      a 3-fold lower K(cat). Three residues in helix I, S286N, V292A, and F295L, were
      essential for S-mephenytoin 4'-hydroxylation activity. On the basis of the
      structure of the closely related enzyme CYP2C5, these residues are unlikely to
      directly contact the substrate during catalysis but are positioned to influence
      the packing of substrate binding site residues and likely substrate access
      channels in the enzyme.

PMID- 11329261
TI  - Monovalent cation-induced conformational change in glucose oxidase leading to
      stabilization of the enzyme.
AB  - Glucose oxidase (GOD) from Aspergillus niger is an acidic dimeric enzyme having a
      high degree of localization of negative charges on the enzyme surface and dimer
      interface. We have studied the effect of monovalent cations on the structure and
      stability of GOD using various optical spectroscopic techniques, limited
      proteolysis, size exclusion chromatography, differential scanning calorimetry,
      and enzymic activity measurements. The monovalent cations were found to influence
      the enzymic activity and tertiary structure of GOD, but no effect on the
      secondary structure of the enzyme was observed. The monovalent cation-stabilized
      GOD was found to have a more compact dimeric structure but lower enzymic activity
      than the native enzyme. The enzyme's K(m) for D-glucose was found to be slightly
      enhanced for the monovalent cation-stabilized enzyme (maximum enhancement of
      about 35% for LiCl) as compared to native GOD. Comparative denaturation studies
      on the native and monovalent cation-stabilized enzyme demonstrated a significant
      resistance of cation-stabilized GOD to urea (about 50% residual activity at 6.5 M
      urea) and thermal denaturation (Delta T(m) maximum of 10 degrees C compared to
      native enzyme). However, pH-induced denaturation showed a destabilization of
      monovalent cation-stabilized GOD as compared to the native enzyme. The
      effectiveness of monovalent cations in stabilizing GOD structure against urea and
      thermal denaturation was found to follow the Hofmeister series: K(+) > Na(+) >
      Li(+).

PMID- 11329262
TI  - Determination of the redox properties of human NADPH-cytochrome P450 reductase.
AB  - Midpoint reduction potentials for the flavin cofactors in human NADPH-cytochrome
      P450 oxidoreductase were determined by anaerobic redox titration of the diflavin
      (FAD and FMN) enzyme and by separate titrations of its isolated FAD/NADPH and FMN
      domains. Flavin reduction potentials are similar in the isolated domains (FAD
      domain E(1) [oxidized/semiquinone] = -286 +/- 6 mV, E(2) [semiquinone/reduced] = 
      371 +/- 7 mV; FMN domain E(1) = -43 +/- 7 mV, E(2) = -280 +/- 8 mV) and the
      soluble diflavin reductase (E(1) [FMN] = -66 +/- 8 mV, E(2) [FMN] = -269 +/- 10
      mV; E(1) [FAD] = -283 +/- 5 mV, E(2) [FAD] = -382 +/- 8 mV). The lack of
      perturbation of the individual flavin potentials in the FAD and FMN domains
      indicates that the flavins are located in discrete environments and that these
      environments are not significantly disrupted by genetic dissection of the
      domains. Each flavin titrates through a blue semiquinone state, with the FMN
      semiquinone being most intense due to larger separation (approximately 200 mV) of
      its two couples. Both the FMN domain and the soluble reductase are purified in
      partially reduced, colored form from the Escherichia coli expression system,
      either as a green reductase or a gray-blue FMN domain. In both cases, large
      amounts of the higher potential FMN are in the semiquinone form. The redox
      properties of human cytochrome P450 reductase (CPR) are similar to those reported
      for rabbit CPR and the reductase domain of neuronal nitric oxide synthase.
      However, they differ markedly from those of yeast and bacterial CPRs, pointing to
      an important evolutionary difference in electronic regulation of these enzymes.

PMID- 11329263
TI  - Stopped-flow kinetic studies of flavin reduction in human cytochrome P450
      reductase and its component domains.
AB  - The reduction by NADPH of the FAD and FMN redox centers in human cytochrome P450
      reductase and its component domains has been studied by rapid-mixing, stopped
      flow spectroscopy. Reduction of the isolated FAD-domain occurs in three
      kinetically resolvable steps. The first represents the rapid formation (>500 s(
      )(1)) of a charge-transfer species between oxidized FAD and NADPH. This is
      followed by an isomerization ( approximately 200 s(-)(1)) to a second charge
      transfer species, characterized by a more intense absorption in the long
      wavelength region. The third step represents hydride transfer from NADPH to FAD
      and is accompanied by a change in the tryptophan fluorescence of the FAD-domain.
      Flavin reduction is reversible, and the observed rate of hydride transfer
      displays a complex dependence on NADPH concentration. Two-electron-reduced FAD
      domain is active in electron transfer reactions with the isolated FMN domain
      through the formation of a weakly associating electron transfer complex.
      Reduction of the CPR by NADPH occurs without direct spectral evidence for the
      formation of charge-transfer species, although the presence of such species is
      inferred indirectly. Transfer of the first hydride ion leads to the accumulation
      of a blue di-semiquinoid species of the reductase, indicating rapid transfer of
      one electron to the FMN domain. The di-semiquinoid species decays on transfer of
      the second hydride ion. A third phase is seen following prolonged incubation with
      NADPH and is assigned to a series of equilibration reactions between different
      redox species of the enzyme as the system relaxes to its thermodynamically most
      stable state. As with the isolated FAD-domain, the first hydride transfer in the
      reductase shows a complex dependence on NADPH concentration. At high NADPH
      concentration, the observed rate of hydride transfer is slow (approximately 20 s(
      1)), and this attenuated rate is attributed to the reversible formation of an
      less active complex resulting from the binding of a second molecule of NADPH. The
      kinetic data are discussed with reference to the potentiometric studies on the
      enzyme and its component domains presented in the preceding paper in this issue
      [Munro, A., Noble, M., Robledo, L., Daff, S., and Chapman, S. (2001) Biochemistry
      40, 1956-1963].

PMID- 11329265
TI  - The structural basis for the perturbed pKa of the catalytic base in 4
      oxalocrotonate tautomerase: kinetic and structural effects of mutations of Phe
      50.
AB  - The amino-terminal proline of 4-oxalocrotonate tautomerase (4-OT) functions as
      the general base catalyst in the enzyme-catalyzed isomerization of beta,gamma
      unsaturated enones to their alpha,beta-isomers because of its unusually low pK(a)
      of 6.4 +/- 0.2, which is 3 units lower than that of the model compound, proline
      amide. Recent studies show that this abnormally low pK(a) is not due to the
      electrostatic effects of nearby cationic residues (Arg-11, Arg-39, and Arg-61)
      [Czerwinski, R. M., Harris, T. K., Johnson, Jr., W. H., Legler, P. M., Stivers,
      J. T., Mildvan, A. S., and Whitman, C. P. (1999) Biochemistry 38, 12358-12366].
      Hence, it may result solely from a low local dielectric constant of 14.7 +/- 0.8
      at the otherwise hydrophobic active site. Support for this mechanism comes from
      the study of mutants of the active site Phe-50, which is 5.8 A from Pro-1 and is
      one of 12 apolar residues within 9 A of Pro-1. Replacing Phe-50 with Tyr does not
      significantly alter k(cat) or K(m) and results in a pK(a) of 6.0 +/- 0.1 for Pro
      1 as determined by (15)N NMR spectroscopy, comparable to that observed for wild
      type. (1)H-(15)N HSQC and 3D (1)H-(15)N NOESY HSQC spectra of the F50Y mutant
      demonstrate its conformation to be very similar to that of the wild-type enzyme.
      In the F50Y mutant, the pK(a) of Tyr-50 is increased by two units from that of a
      model compound N-acetyl-tyrosine amide to 12.2 +/- 0.3, as determined by UV and
      (1)H NMR titrations, yielding a local dielectric constant of 13.4 +/- 1.7, in
      agreement with the value of 13.7 +/- 0.3 determined from the decreased pK(a) of
      Pro-1 in this mutant. In the F50A mutant, the pK(a) of Pro-1 is 7.3 +/- 0.1 by
      (15)N NMR titration, comparable to the pK(a) of 7.6 +/- 0.2 found in the pH vs
      k(cat)/K(m) rate profile, and is one unit greater than that of the wild-type
      enzyme, indicating an increase in the local dielectric constant to a value of
      21.2 +/- 2.6. A loss of structure of the beta-hairpin from residues 50 to 57,
      which covers the active site, and is the site of the mutation, is indicated by
      the disappearance in the F50A mutant of four interstrand NOEs and one turn NOE
      found in wild-type 4-OT. (1)H-(15)N HSQC spectra of the F50A mutant reveal
      widespread and large changes in the backbone (15)N and NH chemical shifts
      including those of Gly residues 48, 51, 53, and 54 causing their loss of
      dispersion at 23 degrees C and their disappearance at 43 degrees C due to rapid
      exchange with solvent. These observations confirm that the active site of the
      F50A mutant is more accessible to the external aqueous environment, causing an
      increase in the local dielectric constant and in the pK(a) of Pro-1. In addition,
      the F50A mutation decreased k(cat) 167-fold and increased K(m) 11-fold from those
      of the wild-type enzyme, suggesting an important role for the hydrophobic
      environment in catalysis, beyond that of decreasing the pK(a) of Pro-1. The F50I
      and F50V mutations destabilize the protein and decrease k(cat) by factors of 58
      and 1.6, and increase K(m) by 3.3- and 3.8-fold, respectively.

PMID- 11329264
TI  - Deletion of the helical motif in the intestinal fatty acid-binding protein
      reduces its interactions with membrane monolayers: Brewster angle microscopy, IR
      reflection-absorption spectroscopy, and surface pressure studies.
AB  - Intestinal fatty acid binding protein (IFABP) appears to interact directly with
      membranes during fatty acid transfer [Hsu, K. T., and Storch, J. (1996) J. Biol.
      Chem. 271, 13317-13323]. The largely alpha-helical "portal" domain of IFABP was
      critical for these protein--membrane interactions. In the present studies, the
      binding of IFABP and a helixless variant of IFABP (IFABP-HL) to acidic monolayers
      of 1,2-dimyristoylphosphatidic acid (DMPA) has been monitored by surface pressure
      measurements, Brewster angle microscopy (BAM), and infrared reflection-absorption
      spectroscopy (IRRAS). Protein adsorption to DMPA exhibited a two phase kinetic
      process consisting of an initial slow phase, arising from protein binding to the
      monolayer and/or direct interfacial adsorption, and a more rapid phase that
      parallels formation of lipid-containing domains. IFABP exhibited more rapid
      changes in both phases than IFABP-HL. The second phase was absent when IFABP
      interacted with zwitterionic monolayers of 1,2-dipalmitoylphosphatidylcholine,
      revealing the important role of electrostatics at this stage. BAM images of DMPA
      monolayers with either protein revealed the formation of domains leading
      eventually to rigid films. Domains of DMPA/IFABP-HL formed more slowly and were
      less rigid than with the wild-type protein. Overall, the IRRAS studies revealed a
      protein-induced conformational ordering of the lipid acyl chains with a
      substantially stronger ordering effect induced by IFABP. The physical
      measurements thus suggested differing degrees of direct interaction between the
      proteins and DMPA monolayers with the IFABP/DMPA interaction being somewhat
      stronger. These data provide a molecular structure rationale for previous kinetic
      measurements indicating that the helical domain is essential for a collision
      based mechanism of fatty acid transfer to phospholipid membranes [Corsico, B.,
      Cistola, D. P., Frieden, C. and Storch, J. (1998) Proc. Natl. Acad. Sci. U.S.A.
      95, 12174-12178].

PMID- 11329266
TI  - Functional estimation of loop-helix boundaries in the lactose permease of
      Escherichia coli by single amino acid deletion analysis.
AB  - Mutants with single amino acid deletions in the loops of lactose permease retain
      activity, while mutants with single deletions in transmembrane helices are
      inactive, and the loop--helix boundaries of helices IV, V, VII, VIII, and IX have
      been approximated functionally by the systematic deletion of single residues
      [Wolin, C. D., and Kaback, H. R. (1999) Biochemistry 38, 8590-8597]. The
      experimental approach is applied here to the remainder of the permease.
      Periplasmic and cytoplasmic loop-helix boundaries for helices I, II, X, XI, and
      XII and the cytoplasmic boundary of helix III are in reasonable agreement with
      structural predictions. In contrast, the periplasmic end of helix III appears to
      be five to eight residues further into the transmembrane domain than predicted.
      Taken together with the previous findings, the analysis estimates that 11 of the
      12 transmembrane helices have an average length of 21 residues. Surprisingly,
      deletion analysis of loop V/VI, helix VI, and loop VI/VII does not yield an
      activity profile typical of the rest of the protein, as individual deletion of
      only three residues in this region abolishes activity. Thus, transmembrane domain
      VI which is probably on the periphery of the 12-helix bundle may make few
      functionally important contacts.

PMID- 11329267
TI  - Molecular determinants for Csk-catalyzed tyrosine phosphorylation of the Src
      tail.
AB  - Phosphorylation of a critical tail tyrosine residue in Src modulates its three
      dimensional structure and protein tyrosine kinase activity. The protein tyrosine
      kinase Csk is responsible for catalyzing the phosphorylation of this key Src
      tyrosine residue, but the detailed molecular basis for Src recognition and
      catalysis is poorly understood. In this study, we investigate this
      phosphorylation event using purified recombinant Csk and Src proteins and
      mutants. It was shown that the apparent k(cat) and K(m) values for Csk
      phosphorylation of catalytically impaired Src (dSrc) are similar to the
      parameters for Csk-catalyzed phosphorylation of the Src family member Lck. The
      SH3 (Src homology 3) and SH2 (Src homology 2) domains of dSrc were fully
      dispensable with respect to rapid phosphorylation, indicating that the catalytic
      domain and tail of dSrc are sufficient for the high efficiency of dSrc as a
      substrate. Of the eight Src tail residues examined, only the fully conserved Glu
      (Y-3 position) and Gln (Y-1 position) investigated by alanine scanning
      mutagenesis caused large reductions (10--40-fold) in dSrc substrate efficiency.
      The Y-3 Glu requirement was stringent as conservative replacements with Asp or
      Gln were no better than Ala whereas replacement of the Y-1 Gln with Ile was
      readily tolerated. Interestingly, en bloc replacement of the tail with a seven
      amino acid consensus sequence derived from a peptide library analysis was no
      better than the wild-type sequence. Surprisingly, the dSrc Y527F protein,
      although not a Csk substrate, enhanced Csk-catalyzed phosphorylation of dSrc.
      These results and other data suggest that Src dimerization (or higher order
      oligomerization) is important for high-efficiency Csk-catalyzed phosphorylation
      of the Src tail.

PMID- 11329268
TI  - Mutations of an epitope hot-spot residue alter rate limiting steps of antigen
      antibody protein-protein associations.
AB  - The antibodies, HyHEL-10 and HyHEL-26 (H10 and H26, respectively), share over 90%
      sequence homology and recognize with high affinity the same epitope on hen egg
      white lysozyme (HEL) but differ in degree of cross-reactivity with mutant
      lysozymes. The binding kinetics, as measured by BIAcore surface plasmon
      resonance, of monovalent Fab from both Abs (Fab10 and Fab26) to HEL and mutant
      lysozymes are best described by a two-step association model consistent with an
      encounter followed by docking that may include conformational changes. In their
      complexes with HEL, both Abs make the transition to the docked phase rapidly. For
      H10, the encounter step is rate limiting, whereas docking is also partially rate
      limiting for H26. The forward rate constants of H10 are higher than those of H26.
      The docking equilibrium as well as the overall equilibrium constant are also
      higher for H10 than for H26. Most of the free energy change of association (Delta
      G degrees) occurs during the encounter phase (Delta G1) of both Abs. H10 derives
      a greater amount and proportion of free energy change from the docking phase
      (Delta G2) than does H26. In the H10--HEL(R21Q) complex, a significant slowing of
      docking results in lowered affinity, a loss of most of Delta G2, and apparently
      faster dissociation. Slower encounter and docking cause lowered affinity and a
      loss of free energy change primarily in the encounter step (Delta G1) of H26 with
      mutant HEL(R21Q). Overall, in the process of complex formation with lysozyme, the
      mutations HEL(R21X) affect primarily the docking phase of H10 association and
      both phases of H26. Our results are consistent with the interpretation that the
      free energy barriers to conformational rearrangement are highest in H26,
      especially with mutant antigen.

PMID- 11329269
TI  - Mutations at position -10 in the lambda PR promoter primarily affect conversion
      of the initial closed complex (RPc) to a stable, closed intermediate (RPi).
AB  - The effects of mutations of --10 T:A to A:T, C:G, or G:C in the lambda P(R)
      promoter on formation of transcriptionally competent open complexes were studied
      by DNAse I footprinting, KMnO(4)-sensitivity, and abortive initiation kinetic
      analysis. The mutations --10A (T:A --> A:T) and --10C significantly reduce k(f),
      the composite rate constant for conversion of closed complexes (RP(c)) to open
      complexes (RP(o)) but do not affect K(B), the equilibrium constant for formation
      of closed complexes. Unlike the other mutants or wild-type P(R), the mutation
      with the largest effect on open complex formation, --10G (T:A --> G:C),
      substantially decreases the occupancy of the promoter. When reduced occupancy is
      taken into account, the calculated effect of the mutation on k(f) is a 20-fold
      reduction. Analysis of open complex formation by a three-step pathway that
      includes an additional intermediate, RP(i), indicates that the primary effect of
      all three mutations is a reduction in the rate of isomerization of RP(c) to
      RP(i), which precedes DNA strand separation. Thus, RNA polymerase holoenzyme must
      recognize specific base pairs in the --10 region of P(R) while the DNA is still
      double-stranded. Comparison of the observed level of stable complexes (RP(i) plus
      RP(o)) with the level of productive complexes (RP(o)) indicates that the --10G
      mutation may also affect the equilibrium between RP(i) and RP(o) at 37 degrees.
      Open complexes formed at the three mutant promoters are approximately 3-5 times
      less stable at 37 degrees than those formed at wild-type P(R).

PMID- 11329270
TI  - Characterization of RNA aptamer binding by the Wilms' tumor suppressor protein
      WT1.
AB  - The interaction of the zinc finger protein WT1 with RNA aptamers has been
      investigated using a quantitative binding assay, and the results have been
      compared to those from a previous study of the DNA binding properties of this
      protein. A recombinant peptide containing the four zinc fingers of WT1 (WT1-ZFP)
      binds to representatives of three specific families of RNA aptamers with apparent
      dissociation constants ranging from 13.8 +/- 1.1 to 87.4 +/- 10.4 nM, somewhat
      higher than the dissociation constant of 4.12 +/- 0.4 nM for binding to DNA. An
      isoform that contains an insertion of three amino acids between the third and
      fourth zinc fingers (WT1[+KTS]-ZFP) also binds to these RNAs with slightly
      reduced affinity (the apparent dissociation constants ranging from 22.8 to 69.8
      nM) but does not bind to DNA. The equilibrium binding of WT1-ZFP to the highest
      affinity RNA molecule was compared to the equilibrium binding to a consensus DNA
      molecule as a function of temperature, pH, monovalent salt concentration, and
      divalent salt concentration. The interaction of WT1-ZFP with both nucleic acids
      is an entropy-driven process. Binding of WT1-ZFP to RNA has a pH optimum that is
      narrower than that observed for binding to DNA. Binding of WT1-ZFP to DNA is
      optimal at 5 mM MgCl(2), while the highest affinity for RNA was observed in the
      absence of MgCl(2). Binding of WT1 to both nucleic acid ligands is sensitive to
      increasing monovalent salt concentration, with a greater effect observed for DNA
      than for RNA. Point mutations in the zinc fingers associated with Denys-Drash
      syndrome have dramatically different effects on the interaction of WT1-ZFP with
      DNA, but a consistent and modest effect on the interaction with RNA. The role of
      RNA sequence and secondary structure in the binding of WT1-ZFP was probed by site
      directed mutagenesis. Results indicate that a hairpin loop is a critical
      structural feature required for protein binding, and that some consensus
      nucleotides can be substituted provided proper base pairing of the stem of the
      hairpin loop is maintained.

PMID- 11329271
TI  - Eosinophil peroxidase catalyzes bromination of free nucleosides and double
      stranded DNA.
AB  - Chronic parasitic infections are a major risk factor for cancer development in
      many underdeveloped countries. Oxidative damage of DNA may provide a mechanism
      linking these processes. Eosinophil recruitment is a hallmark of parasitic
      infections and many forms of cancer, and eosinophil peroxidase (EPO), a secreted
      hemoprotein, plays a central role in oxidant production by these cells. However,
      mechanisms through which EPO may facilitate DNA oxidation have not been fully
      characterized. Here, we show that EPO effectively uses plasma levels of bromide
      as a cosubstrate to brominate bases in nucleotides and double-stranded DNA,
      forming several stable novel brominated adducts. Products were characterized by
      HPLC with on-line UV spectroscopy and electrospray ionization tandem mass
      spectrometry (LC/ESI/MS/MS). Ring assignments for brominated purine bases as
      their 8-bromo adducts were identified by NMR spectroscopy. Using stable isotope
      dilution LC/ESI/MS/MS, we show that while guanine is the preferred purine
      targeted for bromination as a free nucleobase, 8-bromoadenine is the major purine
      oxidation product generated following exposure of double-stranded DNA to either
      HOBr or the EPO/H(2)O(2)/Br(-) system. Bromination of nucleobases was inhibited
      by scavengers of hypohalous acids such as the thioether methionine, but not by a
      large molar excess of primary amines. Subsequently, N-monobromoamines were
      demonstrated to be effective brominating agents for both free nucleobases and
      adenine within intact DNA. A rationale for selective modification of adenine, but
      not guanine, in double-stranded DNA based upon stereochemical criteria is
      presented. Collectively, these results suggest that specific brominated DNA bases
      may serve as novel markers for monitoring oxidative damage of DNA and the
      nucleotide pool by brominating oxidants.

PMID- 11329272
TI  - The eosinophil peroxidase-hydrogen peroxide-bromide system of human eosinophils
      generates 5-bromouracil, a mutagenic thymine analogue.
AB  - Eosinophils use eosinophil peroxidase, hydrogen peroxide (H(2)O(2)), and bromide
      ion (Br(-)) to generate hypobromous acid (HOBr), a brominating intermediate. This
      potent oxidant may play a role in host defenses against invading parasites and
      eosinophil-mediated tissue damage. In this study, we explore the possibility that
      HOBr generated by eosinophil peroxidase might oxidize nucleic acids. When we
      exposed uracil, uridine, or deoxyuridine to reagent HOBr, each reaction mixture
      yielded a single major oxidation product that comigrated on reversed-phase HPLC
      with the corresponding authentic brominated pyrimidine. The eosinophil peroxidase
      H(2)O(2)-Br(-) system also converted uracil into a single major oxidation
      product, and the yield was near-quantitative. Mass spectrometry, HPLC, UV-
      visible spectroscopy, and NMR spectroscopy identified the product as 5
      bromouracil. Eosinophil peroxidase required H(2)O(2) and Br(-) to produce 5
      bromouracil, implicating HOBr as an intermediate in the reaction. Primary and
      secondary bromamines also brominated uracil, suggesting that long-lived
      bromamines also might be physiologically relevant brominating intermediates.
      Human eosinophils used the eosinophil peroxidase-H(2)O(2)-Br(-) system to oxidize
      uracil. The product was identified as 5-bromouracil by mass spectrometry, HPLC,
      and UV--visible spectroscopy. Collectively, these results indicate that HOBr
      generated by eosinophil peroxidase oxidizes uracil to 5-bromouracil. Thymidine
      phosphorylase, a pyrimidine salvage enzyme, transforms 5-bromouracil to 5
      bromodeoxyridine, a mutagenic analogue of thymidine. These findings raise the
      possibility that halogenated nucleobases generated by eosinophil peroxidase exert
      cytotoxic and mutagenic effects at eosinophil-rich sites of inflammation.

PMID- 11329273
TI  - Determination of the hemoglobin surface domains that react with cytochrome b5.
AB  - We have compared the photoinitiated electron-transfer (ET) reaction between
      cytochrome b(5) (b(5)) and zinc mesoporphyrin-substituted hemoglobin [(ZnM)Hb]
      and Hb variants in order to determine whether b(5) binds to the subunit surface
      of either or both Hb chains, or to sites which span the dimer--dimer interface.
      Because the dimer--dimer interface would be disrupted for monomers or alpha beta
      dimers, we studied the reaction of b(5) with alpha ZnM chains and (ZnM)Hb beta
      W37E, which exists as alpha beta dimers in solution. Triplet quenching titrations
      of the ZnHb proteins with Fe(3+)b(5) show that the binding affinity and ET rate
      constants for the alpha-chains are the same when they are incorporated into a Hb
      tetramer or dimer, or exist as monomers. Likewise, the parameters for beta-chains
      in tetramers and dimers differ minimally. In parallel, we have modified the
      surface of the Hb chains by neutralizing the heme propionates through the
      preparation of zinc deuterioporphyrin dimethyl ester hemoglobin, (ZnD-DME)Hb. The
      charge neutralization increases the ET rate constants 100-fold for the alpha
      chains and 40-fold for the beta-chains (but has has little effect on the affinity
      of either chain type for b(5), similar to earlier results for myoglobin).
      Together, these results indicate that b(5) binds to sites at the subunit surface
      of each chain rather than to sites which span the dimer-dimer interface. The
      charge-neutralization results further suggest that b(5) binds over a broad area
      of the subunit face, but reacts only in a minority population of binding
      geometries.

PMID- 11329274
TI  - Desensitization of neuronal nicotinic acetylcholine receptors conferred by N
      terminal segments of the beta 2 subunit.
AB  - Desensitization is a general property of ligand-gated ion channels. Because of a
      wide array of available subunit combinations, it generates different time
      constants for channel closure, thereby modulating the processing of information
      in the brain. Within the family of neuronal nicotinic acetylcholine receptors
      (nAChRs), alpha 3 beta 2 and alpha 3 beta 4 receptors display contrasting
      properties of desensitization. When measured using two-electrode voltage-clamp in
      Xenopus oocytes, desensitization results in current decreases 2 s after
      initiation of acetylcholine application by 94% for alpha 3 beta 2 receptors, but
      only by 6% in the case of alpha 3 beta 4 receptors. Desensitization was analyzed
      by inserting different portions of the beta2 into the beta 4 subunit. Residues 1-
      212 of the beta2 subunit were able to confer 78% desensitization in 2 s, while
      smaller chimeras revealed desensitization in 2 s conferred by residues 1--42
      alone to a level of 50%, by residues 72--89 to a level of 74%, and by residues 96
      -212 to a level of 77%. Some long-term (25 min) effects of desensitization driven
      by acetylcholine were found to rely partially on the same elements, including an
      enhancement mediated by residues 1--95 and 96--212 of the beta 2 subunit
      individually. Our results reveal that desensitization relies independently on
      diverse portions of the extracellular domain of the beta 2 subunit. Phenotype of
      alpha 3 beta 4 involves, in contrast, complex structural requirements involving
      residues dispersed throughout the entire N-terminal domain of the beta 4 subunit.

PMID- 11329275
TI  - pH regulates cation selectivity of poly-(R)-3-hydroxybutyrate/polyphosphate
      channels from E. coli in planar lipid bilayers.
AB  - Poly-(R)-3-hydroxybutyrate/polyphosphate (PHB/polyP) complexes, whether isolated
      from the plasma membranes of bacteria or prepared from the synthetic polymers,
      form ion channels in planar lipid bilayers that are highly selective for Ca(2+)
      over Na(+) at physiological pH. This preference for divalent over monovalent
      cations is attributed to a high density of negative charge along the polyP
      backbone and the higher binding energies of divalent cations. Here we modify the
      charge density of polyP by varying the pH, and observe the effect on cation
      selectivity. PHB/polyP complexes, isolated from E. coli, were incorporated into
      planar lipid bilayers, and unitary current-voltage relations were determined as a
      function of pH. When Ca(2+) was the sole permeant cation, conductance diminished
      steadily from 97 +/- 6 pS at pH 7.4 to 47 +/- 3 pS at pH 5.5. However, in
      asymmetric solutions of Ca(2+) and Na(+), there was a moderate increase in
      conductance from 98 +/- 4 at pH 7.4 to 129 +/- 4 pS at pH 6.5, and a
      substantially larger increase to 178 +/- 6 pS at pH 5.6, signifying an increase
      in Na(+) permeability or disorganization of channel structure. Reversal
      potentials point to a sharp decrease in preference for Ca(2+) over Na(+) over a
      relatively small decrease in pH. Ca(2+) was strongly favored over Na(+) at
      physiological pH, but the channels became nonselective near the pK(2) of
      phosphate (approximately 6.8), and displayed weak selectivity for Na(+) over
      Ca(2+) at acidic pH. Evidently, PHB/polyP complexes are versatile ion carriers
      whose selectivity may be modulated by small adjustments of the local pH. The
      results may be relevant to the physiological function of PHB/polyP channels in
      bacteria and the role of PHB and polyP in the Streptomyces lividans potassium
      channel.

PMID- 11329276
TI  - Mitochondrial phosphate transport protein. Reversions of inhibitory conservative
      mutations identify four helices and a nonhelix protein segment with transmembrane
      interactions and Asp39, Glu137, and Ser158 as nonessential for transport.
AB  - The mitochondrial phosphate transport protein (PTP) has six (A--F) transmembrane
      (TM) helices per subunit of functional homodimer with all mutations referring to
      the subunit of the homodimer. In earlier studies, conservative replacements of
      several residues located either at the matrix end (Asp39/helix A, Glu137/helix C,
      Asp236/helix E) or at the membrane center (His32/helix A, Glu136/helix C) of TM
      helices yielded inactive single mutation PTPs. Some of these residues were
      suggested to act as phosphate ligands or as part of the proton cotransport path.
      We now show that the mutation Ser158Thr, not part of a TM helix but located near
      the center of the matrix loop (Ile141--Ser171) between TM helices C and D,
      inactivates PTP and is thus also functionally relevant. On the other side of the
      membrane, the single mutation Glu192Asp at the intermembrane space end of TM
      helix D yields a PTP with 33% wild-type activity. We constructed double mutants
      by adding this mutation to the six transport-inactivating mutations. Transport
      was detected only in those with Asp39Asn, Glu137Gln, or Ser158Thr. We conclude
      that TM helix D can interact with TM helices A and C and matrix loop Ile141-
      Ser171 and that Asp39, Glu137, and Ser158 are not essential for phosphate
      transport. Since our results are consistent with residues present in all 12
      functionally identified members of the mitochondrial transport protein (MTP)
      family, they lead to a general rule that specifies MTP residue types at 7
      separate locations. The conformations of all the double mutation PTPs (except
      that with the matrix loop Ser158Thr) are significantly different from those of
      the single mutation PTPs, as indicated by their very low liposome incorporation
      efficiency and their requirement for less detergent (Triton X-100) to stay in
      solution. These dramatic conformational differences also suggest an interaction
      between TM helices D and E. The results are discussed in terms of TM helix
      movements and changes in the PTP monomer/dimer ratio.

PMID- 11329277
TI  - Phosphorylation of molluscan twitchin by the cAMP-dependent protein kinase.
AB  - Catch in certain molluscan muscles is released by an increase in cAMP, and it was
      suggested that the target of cAMP-dependent protein kinase (PKA) is the high
      molecular weight protein twitchin [Siegman, M. J., Funabara, J., Kinoshita, S.,
      Watabe, S., Hartshorne, D. J., and Butler, T. M. (1998) Proc. Natl. Acad. Sci.
      U.S.A. 95, 5384-5388]. This study was carried out to investigate the
      phosphorylation of twitchin by PKA. Twitchin was isolated from Mytilus catch
      muscles and was phosphorylated by PKA to a stoichiometry of about 3 mol of P/mol
      of twitchin. There was no evidence of twitchin autophosphorylation. Two
      phosphorylated peptides were isolated and sequenced, termed D1 and D2. Additional
      cDNA sequence for twitchin was obtained, and the D2 site was located at the C
      terminal side of the putative kinase domain in a linker region between two
      immunoglobulin C2 repeats. Excess PKA substrates, e.g., D1 and D2, blocked the
      reduction in force on addition of cAMP, confirming the role for PKA in regulating
      catch. Papain proteolysis of (32)P-labeled twitchin from permeabilized muscles
      showed that the D1 site represented about 50% of the (32)P labeling. Proteolysis
      of in-situ twitchin with thermolysin suggested that the D1 and D2 sites were at
      the N- and C-terminal ends of the molecule, respectively. Thermolysin proteolysis
      also indicated that D1 and D2 were major sites of phosphorylation by PKA. The
      direct phosphorylation of twitchin by PKA is consistent with a regulatory role
      for twitchin in the catch mechanism and probably involves phosphorylation at the
      D1 and D2 sites.

PMID- 11329278
TI  - Identification by mass spectrometry of a new alpha-tubulin isotype expressed in
      human breast and lung carcinoma cell lines.
AB  - The extensive C-terminal molecular heterogeneity of alpha- and beta-tubulin is a
      consequence of multiple isotypes, the products of distinct genes, that undergo
      several posttranslational modifications. These include polyglutamylation and
      polyglycylation of both subunits, reversible tyrosination and removal of the
      penultimate glutamate from alpha-tubulin, and phosphorylation of the beta III
      isotype. A mass spectrometry-based method has been developed for the analysis of
      the C-terminal diversity of tubulin from human cell lines. Total cell extracts
      are resolved by SDS--PAGE and transferred to nitrocellulose, and the region of
      the blot corresponding to tubulin (approximately 50 kDa) was excised and digested
      with CNBr to release the highly divergent C-terminal tubulin fragments. The
      masses of the human alpha- and beta-tubulin CNBr-derived C-terminal peptides are
      all in the 1500--4000 Da mass range and can be analyzed directly by MALDI-TOF
      mass spectrometry in the negative ion mode without significant interference from
      other released peptides. In this study, the tubulin isotype diversity in MDA-MB
      231, a human breast carcinoma cell line, and A549, a human non-small lung cancer
      cell line, is reported. The major tubulin isotypes present in both cell lines are
      k-alpha 1 and beta 1. Importantly, we report a previously unknown alpha isotype
      present at significant levels in both cell lines. Moreover, the degree of
      posttranslational modifications to all isotypes was limited. Glu-tubulin, in
      which the C-terminal tyrosine of alpha-tubulin is removed, was not detected. In
      contrast to mammalian neuronal tubulin which exhibits extensive
      polyglutamylation, only low-level monoglutamylation of the k-alpha 1 and beta 1
      isotypes was observed in these two human cell lines.

PMID- 11329279
TI  - Importance of internal regions and the overall length of tropomyosin for actin
      binding and regulatory function.
AB  - Tropomyosin (Tm) binds along actin filaments, one molecule spanning four to seven
      actin monomers, depending on the isoform. Periodic repeats in the sequence have
      been proposed to correspond to actin binding sites. To learn the functional
      importance of length and the internal periods we made a series of progressively
      shorter Tms, deleting from two up to six of the internal periods from rat
      striated alpha-TM (dAc2--3, dAc2--4, dAc3--5, dAc2--5, dAc2--6, dAc1.5--6.5).
      Recombinant Tms (unacetylated) were expressed in Escherichia coli. Tropomyosins
      that are four or more periods long (dAc2--3, dAc2--4, and dAc3--5) bound well to
      F-actin with troponin (Tn). dAc2--5 bound weakly (with EGTA) and binding of
      shorter mutants was undetectable in any condition. Myosin S1-induced binding of
      Tm to actin in the tight Tm-binding "open" state did not correlate with actin
      binding. dAc3--5 and dAc2--5 did not bind to actin even when the filament was
      saturated with S1. In contrast, dAc2--3 and dAc2--4 did, like wild-type-Tm,
      requiring about 3 mol of S1/mol of Tm for half-maximal binding. The results show
      the critical importance of period 5 (residues 166--207) for myosin S1-induced
      binding. The Tms that bound to actin (dAc2--3, dAc2--4, and dAc3--5) all fully
      inhibited the actomyosin ATPase (+Tn) in EGTA. In the presence of Ca(2+), relief
      of inhibition by these Tms was incomplete. We conclude (1) four or more actin
      periods are required for Tm to bind to actin with reasonable affinity and (2)
      that the structural requirements of Tm for the transition of the regulated
      filament from the blocked-to-closed/open (relief of inhibition by Ca(2+)) and the
      closed-to-open states (strong Tm binding to actin-S1) are different.

PMID- 11329280
TI  - Effect of salts on the stability and folding of staphylococcal nuclease.
AB  - The stability and folding kinetics of wild-type and a mutant staphylococcal
      nuclease (SNase) at neutral pH are significantly perturbed by the presence of
      moderate to high concentrations of salts. Very substantial increases in stability
      toward thermal and urea denaturation were observed; for example, 0.4 M sodium
      sulfate increased the free energy of wild-type SNase by more than 2 kcal/mol. For
      the NCA SNase mutant, the presence of the salts abolished the cold denaturation
      observed at neutral pH with this variant, and substantially increased its
      stability. Significant effects of salts on the kinetics of refolding were also
      observed. For NCA SNase, the presence of the salts markedly increased the folding
      rates (up to 5-fold). On the other hand, chloride, in particular, substantially
      decreased the rate of folding of the wild-type protein. Since the rates of the
      slow phases due to proline isomerization were increased by salt, these steps must
      be coupled to conformational processes. Fluorescence energy transfer between the
      lone tryptophan (Trp140) and an engineered fluorescent acceptor at residue 64
      revealed that the addition of a high concentration of KCl led to the formation of
      a transient folding intermediate not observed at lower salt concentrations, and
      in which residues 140 and 64 were much closer than in the native state. The salt
      induced effects on the kinetics of folding are attributed to the enhanced
      stability of the transient folding intermediates. It is likely that the
      combination of the high net charge, due to the high isoelectric point, and the
      relatively low intrinsic hydrophobicity, leads to staphylococcal nuclease having
      only marginal stability at neutral pH. The salt-induced effects on the structure,
      stability, and kinetics of staphylococcal nuclease are attributed to the binding
      of counterions, namely, anions, resulting in minimization of intramolecular
      electrostatic repulsion. This leads to increased stability, more structure, and
      greater compactness, as observed. Consequently, localized electrostatic repulsion
      is present at neutral pH in SNase, probably contributing to its marginal
      stability. The results suggest that, in general, marginally stable globular
      proteins will be significantly stabilized by salts under conditions where they
      have a substantial net charge.

PMID- 11329281
TI  - Cardiac creatine kinase metabolite compartments revealed by NMR magnetization
      transfer spectroscopy and subcellular fractionation.
AB  - In the perfused rat heart NMR inversion transfer revealed the existence of a
      compartment of ATP not exchanging through creatine kinase (CK), as demonstrated
      by an apparent discrepancy between the forward (F(f)) and reverse (F(r)) CK flux
      if this compartment was neglected in the analysis [Joubert et al. (2000) Biophys.
      J. 79, 1-13]. To localize this compartment, CK fluxes were measured by inversion
      of PCr (inv-PCr) or gamma ATP (inv-ATP), and the distribution of metabolites
      between mitochondria and cytosol was studied by subcellular fractionation.
      Physiological conditions were designed to modify the concentration and
      distribution of CK metabolites (control, adenylate depletion, inhibition of
      respiration, KCl arrest). Depending on cardiac activity, mitochondrial ATP (mito
      ATP) assessed by fractionation varied from 11% to 30% of total ATP. In addition,
      the apparent flux discrepancy increased together with mito-ATP (F(f)/F(r) ranged
      from 0.85 to 0.50 in inv-PCr and from 1.13 to 1.88 in inv-ATP). Under conditions
      masking the influence of the ATP-P(i) exchange on CK flux, the ATP compartment
      could be directly quantified by the apparent flux discrepancy; its size was
      similar to that of mito-ATP measured by fractionation. Thus NMR inversion
      technique is a potential tool to assess metabolite compartmentation in the whole
      organ.

PMID- 11329283
TI  - Amyloid-induced aggregation and precipitation of soluble proteins: an
      electrostatic contribution of the Alzheimer's beta(25-35) amyloid fibril.
AB  - Amyloid-induced aggregation and precipitation of soluble proteins were
      investigated in vitro using the amyloid fibrils of the beta(25--35) peptide, a
      cytotoxic fragment of the Alzheimer's beta-peptide at positions 25--35. The
      aggregation rate of firefly luciferase was found to be modulated by both a
      chaperone molecule DnaK and the beta(25--35) amyloid, but their effects were
      opposite in direction. The amyloid fibril drastically facilitated the luciferase
      aggregation, which may define a kind of anti-chaperone activity. The effect of
      the beta(25--35) amyloid to promote protein aggregation and precipitation was
      further demonstrated for a wide variety of target proteins. The amount of
      coprecipitation was well correlated with the predicted isoelectric point of the
      target proteins, indicating that the interaction between the beta(25--35) amyloid
      and the target was driven by an electrostatic force between them. This view was
      confirmed by the experiments using an electrically neutral mutant peptide,
      beta(25--35)KA. It was also found that clustering of the beta(25--35) peptide to
      form amyloid and the conformation of the target protein are additional factors
      that determine the strength of the amyloid-protein interaction. Spectroscopic and
      electron microscopic methods have revealed that the proteins coprecipitated with
      the beta(25--35) amyloid formed amorphous aggregates deposited together with the
      amyloid fibrils. The conformation of protein molecules left in the residual
      soluble fraction was also damaged in the amyloid-containing solution. As a
      summary, this study has proposed a scheme for events related to the nonspecific
      amyloid-protein interaction, which may play substantial roles in in vivo
      conditions.

PMID- 11329282
TI  - A comparative study of peptide models of the alpha-domain of alpha-lactalbumin,
      lysozyme, and alpha-lactalbumin/lysozyme chimeras allows the elucidation of
      critical factors that contribute to the ability to form stable partially folded
      states.
AB  - alpha-Lactalbumin (alpha LA) forms a well-populated equilibrium molten globule
      state, while the homologous protein hen lysozyme does not. alpha LA is a two
      domain protein and the alpha-domain is more structured in the molten globule
      state than is the beta-domain. Peptide models derived from the alpha-subdomain
      that contain the A, B, D, and 3(10) helices of alpha LA are capable of forming a
      molten globule state in the absence of the remainder of the protein. Here we
      report comparative studies of a peptide model derived from the same region of hen
      lysozyme and a set of chimeric alpha-lactalbumin--lysozyme constructs. Circular
      dichroism, dynamic light scattering, sedimentation equilibrium, and fluorescence
      experiments indicate that the lysozyme construct does not fold. Chimeric
      constructs were prepared to probe the origins of the difference in the ability of
      the two isolated subdomains to fold. The first consists of the A and B helices of
      alpha LA cross-linked to the D and C-terminal 3(10) helices of lysozyme. This
      construct is highly helical, while a second construct that contains the A and B
      helices of lysozyme cross-linked to the D and 3(10) helices of alpha LA does not
      fold. Furthermore, the disulfide cross-linked homodimer of the alpha LA AB
      peptide is helical, while the homodimer of the lysozyme AB peptide is
      unstructured. Thus, the AB helix region of alpha LA appears to have an intrinsic
      ability to form structure as long as some relatively nonspecific interactions can
      be made with other regions of the protein. Our studies show that the A and B
      helices plays a key role in the ability of the respective alpha-subdomains to
      fold.

PMID- 11329284
TI  - Effects of noncovalent and covalent FAD binding on the redox and catalytic
      properties of p-cresol methylhydroxylase.
AB  - Each flavoprotein subunit (alpha or PchF) of the alpha(2)beta(2) flavocytochrome
      p-cresol methylhydroxylase (PCMH) from Pseudomonas putida contains FAD covalently
      attached to Tyr384. PCMH oxidizes p-cresol to 4-hydroxybenzyl alcohol, which is
      oxidized subsequently by PCMH to 4-hydroxybenzaldehyde. The Y384F mutant form of
      PchF (apo-PchF[Y384F]) displayed stoichiometric noncovalent FAD binding.
      PchF[Y384F]FAD associated with the cytochrome subunit (beta or PchC) (producing
      PCMH[Y384F]), although not as avidly as with wild-type PchF containing covalently
      bound FAD (PchF(C)). Dramatic increases in the two-electron E(m,7) (NHE) values
      for FAD were observed when it bound noncovalently to either apo-PchF or apo
      PchF[Y384F], and the two-electron E(m,7) value for FAD was increased further by
      about 75 mV upon covalent binding to PchF, i.e., PchF(C). The E(m,7) values
      increased by approximately 20 and 45 mV, respectively, when PchF(C) and
      PchF[Y384F]FAD associated with PchC. The two-electron E(m,7) for covalently bound
      FAD in PCMH is 84 mV, the highest measured for a flavoprotein. The values for the
      one-electron redox potentials (E(m,7), NHE) for FAD were measured also for
      various forms of PchF. Under anaerobiosis, the reduction of PchF[Y384F]FAD by
      substrates was similar to that observed previously for PchF containing
      noncovalently bound FAD. Stopped-flow kinetic studies indicated a rapid substrate
      reduction of the FAD and heme in PCMH[Y384F] which produced PchF[Y384F]FAD(rad) x
      PchC, the mutant enzyme containing the flavin radical and reduced heme. These
      experiments also revealed a slow reduction of unassociated PchC(ox) by
      PchF[Y384F]FAD(rad) x PchC. Steady-state kinetic studies of the reaction of
      PCMH[Y384F] with p-cresol indicated that the K(m) for this substrate was
      unchanged relative to that of PCMH, but that the k(cat) was diminished by an
      order of magnitude. The data indicate that the covalent attachment of FAD to PchF
      assists catalysis by raising the E(m,7) of the flavin. Contributions to this
      effect likely result from conformational changes.

PMID- 11329285
TI  - Site-directed mutagenesis of PsaA residue W693 affects phylloquinone binding and
      function in the photosystem I reaction center of Chlamydomonas reinhardtii.
AB  - To investigate the environment of the phylloquinone secondary electron acceptor
      A(1) within the photosystem I reaction center, we have carried out site-directed
      mutagenesis of two tryptophan residues (W693 and W702) in the PsaA subunit of
      Chlamydomonas reinhardtii. One of these conserved tryptophans (W693) is predicted
      to be close to the phylloquinone and has been implicated in the interaction of
      A(1) with an aromatic residue through pi--pi stacking. We find that replacement
      of W702 with either histidine or leucine has no effect on the electronic
      structure of A(1)(*-) or on forward electron transfer from A(1)(*-) to the iron-
      sulfur center F(x). In contrast, the same mutations of W693 alter the electronic
      structure of the photoaccumulated A(1)(*-) and slow forward electron transfer as
      measured by the decay of the electron spin-polarized signal arising from the
      P700(*+)/A(1)(*-) radical pair. These results provide support for the hypothesis
      that W693 has a role in poising the redox potential of A(1)/A(1)(*-) so it can
      reduce F(x), and they indirectly provide evidence for electron transfer along the
      PsaA-side branch of cofactors in PSI.

PMID- 11329286
TI  - Triplet formation on a monomeric chlorophyll in the photosystem II reaction
      center as studied by time-resolved infrared spectroscopy.
AB  - The process of formation of the triplet state of chlorophyll in the photosystem
      II (PS II) reaction center complex was studied by means of time-resolved infrared
      (IR) spectroscopy. Using a dispersive-type IR spectrometer with a time resolution
      of approximately 55 ns, transient spectra in the C=O stretching region (1760-
      1600 cm(-1)) were measured at 77 K. The data were analyzed by singular-value
      decomposition and subsequent least-squares fitting. Two distinct spectral
      components having different kinetic behaviors were resolved. One had spectral
      features characterized by negative peaks at 1740 and 1680 cm(-1) and an overall
      positive background and was assigned to the P(680)(+)Phe(-)/P(680)Phe radical
      pair by static FTIR measurements of the P(680)(+)/P(680) and Phe(-)/Phe
      differences. The other had prominent negative and positive peaks at 1668 and 1628
      cm(-1), respectively, which were previously assigned to the keto C==O change upon
      triplet formation of the monomeric chlorophyll denoted as Chl(T) [Noguchi, T.,
      Tomo, T., and Inoue, Y. (1998) Biochemistry 37, 13614-13625]. The former
      component of P(680)(+)Phe(-)/P(680)Phe exhibited a multiphasic decay with time
      constants of 77 ns (75%), 640 ns (18%), 8.3 micros (4%), and 0.3 ms (3%), while
      the latter component of (3)Chl(T)/Chl(T) was formed with a single-exponential
      rise with a time constant of 57 ns and had a lifetime of 1.5 ms. From the
      observations that only the two spectral components were resolved without any
      other triplet intermediates and the time constant of (3)Chl(T) formation roughly
      agreed with or seemed even faster than that of the major phase of the
      P(680)(+)Phe(-) decay, two alternative mechanisms of triplet formation are
      proposed. (i) (3)Chl(T) is directly formed from P(680)(+)Phe(-) by charge
      recombination at Chl(T), and (ii) (3)P(680) is formed, and then the triplet is
      transferred to Chl(T) with a time constant of much less than 50 ns. The location
      of Chl(T) in the D1 subunit as the monomer chlorophyll corresponding to the
      accessory bacteriochlorophyll in the L subunit of purple bacteria is favored to
      explain the former mechanism as well as the triplet properties reported in the
      literature. The physiological role of the triplet formation on Chl(T) is also
      discussed.

PMID- 11329287
TI  - Photoinduced electron transfer in the cytochrome c/cytochrome c oxidase complex
      using thiouredopyrenetrisulfonate-labeled cytochrome c. Optical multichannel
      detection.
AB  - Intramolecular electron transfer in the electrostatic cytochrome c
      oxidase/cytochrome c complex was investigated using a novel photoactivatable dye.
      Laser photolysis of thiouredopyrenetrisulfonate (TUPS), covalently linked to
      cysteine 102 on yeast iso-1-cytochrome c, generates a triplet state of the dye,
      which donates an electron to cytochrome c, followed by electron transfer to
      cytochrome c oxidase. Time-resolved optical absorption difference spectra were
      collected at delay times from 100 ns to 200 ms between 325 and 650 nm. On the
      basis of singular value decomposition (SVD) and multiexponential fitting, three
      apparent lifetimes were resolved. A sequential kinetic mechanism is proposed from
      which the microscopic rate constants and spectra of the intermediates were
      determined. The triplet state of TUPS donates an electron to cytochrome c with a
      forward rate constant of approximately 2.0 x 10(4) s(-1). A significant fraction
      of the triplet returns back to the ground state on a similar time scale. The
      reduction of cytochrome c is followed by faster electron transfer from cytochrome
      c to Cu(A), with the equilibrium favoring the reduced cytochrome c. Subsequently,
      Cu(A) equilibrates with heme a with an apparent rate constant of approximately 1
      x 10(4) s(-1). On a millisecond time scale, the oxidized TUPS returns to the
      ground state and heme a becomes reoxidized. The extracted intermediate spectra
      are in excellent agreement with model spectra of the postulated intermediates,
      supporting the proposed mechanism.

PMID- 11329288
TI  - Multiple inhibitor analysis of the brequinar and leflunomide binding sites on
      human dihydroorotate dehydrogenase.
AB  - Brequinar and the active metabolite of leflunomide, A77 1726, have been clearly
      shown to inhibit human dihydroorotate dehydrogenase (DHODH), but conflicting
      mechanisms for their inhibition have been reported. DHODH catalyses the
      conversion of dihydroorotate (DHO) to orotate concurrent with the reduction of
      ubiquinone. This study presents data that indicates brequinar is a competitive
      inhibitor versus ubiquinone; A77 1726 is noncompetitive versus ubiquinone and
      both are uncompetitive versus DHO. 2-Phenyl 5-quinolinecarboxylic acid (PQC), the
      core moiety of brequinar also shows competitive inhibition versus ubiquinone.
      Multiple inhibition experiments indicate that PQC (and thus brequinar) and A77
      1726 have overlapping binding sites. Both PQC and A77 1726 are also mutually
      exclusive with barbituric acid (a competitive inhibitor versus DHO). In addition,
      we failed to observe brequinar binding to E.orotate by isothermal titration
      calorimetry (ITC). These results indicate that the E.DHO.inhibitor and
      E.orotate.inhibitor ternary complexes do not form. The absence of these complexes
      is consistent with the two-site ping-pong mechanism reported for DHODH. This
      kinetic data suggests that recent crystal structures of human DHODH complexed
      with orotate and A77 1726 or brequinar may not represent the relevant
      physiological binding sites for these inhibitors [Liu, S., Neidhardt, E. A.,
      Grossman, T. H., Ocain, T., and Clardy J. (2000) Structure 8, 25-33].

PMID- 11329290
TI  - Distinct reactions catalyzed by bacterial and yeast trans-aconitate
      methyltransferases.
AB  - The trans-aconitate methyltransferase from the bacterium Escherichia coli
      catalyzes the monomethyl esterification of trans-aconitate and related compounds.
      Using two-dimensional (1)H/(13)C nuclear magnetic resonance spectroscopy, we show
      that the methylation is specific to one of the three carboxyl groups and further
      demonstrate that the product is the 6-methyl ester of trans-aconitate (E-3
      carboxy-2-pentenedioate 6-methyl ester). A similar enzymatic activity is present
      in the yeast Saccharomyces cerevisiae. Although we find that yeast trans
      aconitate methyltransferase also catalyzes the monomethyl esterification of trans
      aconitate, we identify that the methylation product of yeast is the 5-methyl
      ester (E-3-carboxyl-2-pentenedioate 5-methyl ester). The difference in the
      reaction catalyzed by the two enzymes may explain why a close homologue of the E.
      coli methyltransferase gene is not found in the yeast genome and furthermore
      suggests that these two enzymes may play distinct roles. However, we demonstrate
      here that the conversion of trans-aconitate to each of these products can
      mitigate its inhibitory effect on aconitase, a key enzyme of the citric acid
      cycle, suggesting that these methyltransferases may achieve the same
      physiological function with distinct chemistries.

PMID- 11329289
TI  - Characterization of the Glu and Asp residues in the active site of human beta
      hexosaminidase B.
AB  - Human beta-hexosaminidase A (alpha beta) and B (beta beta) are composed of
      subunits (alpha and beta) that are 60% identical and have been grouped with other
      evolutionarily related glycosidases into "Family 20". The three-dimensional
      structure of only one Family 20 member has been elucidated, a bacterial
      chitobiase. This enzyme shares primary structure homology with both the human
      subunits only in its active-site region, and even in this restricted area, the
      level of identity is only 26%. Thus, the validity of the molecular model for the
      active site of the human enzyme based on chitobiase must be determined
      experimentally. In this report, we analyze highly purified mutant forms of human
      hexosaminidase B that have had conservative substitutions made at Glu and Asp
      residues predicted by the chitobiase model to be part of its active site.
      Mutation of beta Glu(355) to Gln reduces k(cat) 5000-fold with only a small
      effect on K(m), while also shifting the pH optimum. These effects are consistent
      with assignment of this residue as the acid/base catalytic residue. Similarly,
      mutation of beta Asp(354) to Asn reduced k(cat) 2000-fold while leaving K(m)
      essentially unaltered, consistent with assignment of this residue as the residue
      that interacts with the substrate acetamide group to promote its attack on the
      anomeric center. These data in conjunction with the mutagenesis studies of
      Asp(241) and Glu(491) indicate that the molecular model is substantially accurate
      in its identification of catalytically important residues.

PMID- 11329291
TI  - Methane monooxygenase component B mutants alter the kinetics of steps throughout
      the catalytic cycle.
AB  - Component interactions play important roles in the regulation of catalysis by
      methane monooxygenase (MMO). The binding of component B (MMOB) to the hydroxylase
      component (MMOH) has been shown in previous studies to cause structural changes
      in MMOH that result in altered thermodynamic and kinetic properties during the
      reduction and oxygen binding steps of the catalytic cycle. Here, specific amino
      acid residues of MMOB that play important roles in the interconversion of several
      intermediates of the MMO cycle have been identified. Both of the histidine
      residues in Methylosinus trichosporium OB3b MMOB (H5 and H33) were chemically
      modified by diethylpyrocarbonate (DEPC). Although the DEPC--MMOB species
      exhibited only minor changes relative to unmodified MMOB in steady-state MMO
      turnover, large decreases in the formation rate constants of the reaction cycle
      intermediates, compound P and compound Q, were observed. The site specific
      mutants H5A, H33A, and H5A/H33A were made and characterized. H5A and wild type
      MMOB elicited similar steady-state and transient kinetics, although the mutant
      caused a slightly lower rate constant for Q formation. Conversely, H33A exhibited
      a >50-fold decrease in the P formation rate constant, which resulted in slower
      formation of Q. The kinetics of the double mutant (H5A/H33A) were similar to
      those of H33A, suggesting that the highly conserved residue, H33, has the most
      significant effect on the efficient progress of the cycle. Ongoing NMR
      investigations of residues perturbed by formation of the MMOH-MMOB complex
      suggested construction of the MMOB N107G/S109A/S110A/T111A quadruple mutant. This
      mutant was found to elicit a nearly 2-fold increase in specific activity for
      steady-state MMO turnover of large substrates such as furan and nitrobenzene but
      caused no similar increase for the physiological substrate, methane. While the
      quadruple mutant did not have a significant effect on P and Q formation, it
      caused an almost 3-fold increase in the decay rate constant of Q for furan
      oxidation and a 2-fold faster product release rate constant for p-nitrophenol
      resulting from nitrobenzene oxidation. Conversely, this mutant caused the Q decay
      rate constant to decrease 7-fold for methane oxidation but left the product
      release step unaffected. These results show for the first time that MMOB exerts
      influence at late as well as early steps in the catalytic cycle. They also
      suggest that MMOB plays a critical role in determining the ability of MMO to
      distinguish between methane and larger substrates.

PMID- 11329292
TI  - Thermal stabilization of the catalytic domain of botulinum neurotoxin E by
      phosphorylation of a single tyrosine residue.
AB  - The catalytic domain of clostridial neurotoxins is a substrate of tyrosine
      specific protein kinases. The functional role of tyrosine phosphorylation and
      also the number and location of its (their) phosphorylation site(s) are yet
      elusive. We have used the recombinant catalytic domain of botulinum neurotoxin E
      (BoNT E) to examine these issues. Bacterially expressed and purified BoNT E
      catalytic domain was fully active, and was phosphorylated in vitro by the
      tyrosine-specific kinase Src. Tyrosine phosphorylation of the catalytic domain
      increased the protein thermal stability without affecting its proteolytic
      activity. Covalent modification of the endopeptidase promoted a disorder-to-order
      transition, as evidenced by the 35% increment of the alpha-helical content, which
      resulted in a 4 degrees C increase of its denaturation temperature. Site-directed
      replacement of tyrosine at position 67 completely abolished phosphate
      incorporation by Src. Constitutively unphosphorylated endopeptidase mutants
      exhibited functional properties virtually identical to those displayed by the
      nonphosphorylated wild-type catalytic domain. These findings indicate the
      presence of a single phosphorylation site in the catalytic domain of clostridial
      neurotoxins, and that its covalent modification primarily modulates the protein
      thermostability.

PMID- 11329293
TI  - The role of Glu39 in MnII binding and oxidation by manganese peroxidase from
      Phanerochaete chrysoporium.
AB  - Manganese peroxidase (MnP) is a heme-containing enzyme produced by white-rot
      fungi and is part of the extracellular lignin degrading system in these
      organisms. MnP is unique among Mn binding enzymes in its ability to bind and
      oxidize Mn(II) and efficiently release Mn(III). Initial site-directed mutagenesis
      studies identified the residues E35, E39, and D179 as the Mn binding ligands.
      However, an E39D variant was recently reported to display wild-type Mn binding
      and rate of oxidation, calling into question the role of E39 as an Mn ligand. To
      investigate this hypothesis, we performed computer modeling studies which
      indicated metal-ligand bond distances in the E39D variant and in an E35D--E39D-
      D179E triple variant which might allow Mn binding and oxidation. To test the
      model, we reconstructed the E35D and E39D variants used in the previous study, as
      well as an E39A single variant and the E35D--E39D--D179E triple variant of MnP
      isozyme 1 from Phanerochaete chrysosporium. We find that all of the variant
      proteins are impaired for Mn(II) binding (K(m) increases 20--30-fold) and Mn(II)
      oxidation (k(cat) decreases 50--400-fold) in both the steady state and the
      transient state. In particular, mutation of the E39 residue in MnP decreases both
      Mn binding and oxidation. The catalytic efficiency of the E39A variants decreased
      approximately 10(4)-fold, while that of the E39D variant decreased approximately
      10(3)-fold. Contrary to initial modeling results, the triple variant performed
      only as well as any of the single Mn ligand variants. Interestingly, the
      catalytic efficiency of the triple variant decreased only 10(4)-fold, which is
      approximately 10(2)-fold better than that reported for the E35Q--D179N double
      variant. These combined studies indicate that precise geometry of the Mn ligands
      within the Mn binding site of MnP is essential for the efficient binding,
      oxidation, and release of Mn by this enzyme. The results clearly indicate that
      E39 is a Mn ligand and that mutation of this ligand decreases both Mn binding and
      the rate of Mn oxidation.

PMID- 11329294
TI  - Characterization of the coral allene oxide synthase active site with UV-visible
      absorption, magnetic circular dichroism, and electron paramagnetic resonance
      spectroscopy: evidence for tyrosinate ligation to the ferric enzyme heme iron.
AB  - Coral allene oxide synthase (AOS), a hemoprotein with weak sequence homology to
      catalase, is the N-terminal domain of a naturally occurring fusion protein with
      an 8R-lipoxygenase. AOS converts 8R-hydroperoxyeicosatetraenoic acid to the
      corresponding allene oxide. The UV--visible absorption and magnetic circular
      dichroism spectra of ferric AOS and of its cyanide and azide complexes, and the
      electron paramagnetic resonance spectra of native AOS (high-spin, g = 6.56, 5.22,
      2.00) and of its cyanide adduct (low-spin, g = 2.86, 2.24, 1.60) closely resemble
      the corresponding spectra of bovine liver catalase (BLC). These results provide
      strong evidence for tyrosinate ligation to the heme iron of AOS as has been
      established for catalases. On the other hand, the positive circular dichroism
      bands in the Soret region for all three derivatives of ferric AOS are almost the
      mirror image of those in catalase. In addition, the cyanide affinity of native
      AOS (K(d) = 10 mM at pH 7) is about 3 orders of magnitude lower than that of BLC.
      Thus, while these results conclusively support a common tyrosinate-ligated heme
      in AOS as in catalase, significant differences exist in the interaction between
      their respective heme prosthetic groups and protein environments, and in the
      access of small molecules to the heme iron.

PMID- 11329295
TI  - Pig liver carnitine palmitoyltransferase I, with low Km for carnitine and high
      sensitivity to malonyl-CoA inhibition, is a natural chimera of rat liver and
      muscle enzymes.
AB  - The outer mitochondrial membrane enzyme carnitine palmitoyltransferase I (CPTI)
      catalyzes the initial and regulatory step in the beta-oxidation of fatty acids.
      The genes for the two isoforms of CPTI-liver (L-CPTI) and muscle (M-CPTI) have
      been cloned and expressed, and the genes encode for enzymes with very different
      kinetic properties and sensitivity to malonyl-CoA inhibition. Pig L-CPTI encodes
      for a 772 amino acid protein that shares 86 and 62% identity, respectively, with
      rat L- and M-CPTI. When expressed in Pichia pastoris, the pig L-CPTI enzyme shows
      kinetic characteristics (carnitine, K(m) = 126 microM; palmitoyl-CoA, K(m) = 35
      microM) similar to human or rat L-CPTI. However, the pig enzyme, unlike the rat
      liver enzyme, shows a much higher sensitivity to malonyl-CoA inhibition (IC(50) =
      141 nM) that is characteristic of human or rat M-CPTI enzymes. Therefore, pig L
      CPTI behaves like a natural chimera of the L- and M-CPTI isotypes, which makes it
      a useful model to study the structure--function relationships of the CPTI
      enzymes.

PMID- 11329296
TI  - Ff gene 5 protein has a high binding affinity for single-stranded
      phosphorothioate DNA.
AB  - The gene 5 protein (g5p) of Ff bacteriophages is a well-studied model ssDNA
      binding protein that binds cooperatively to the Ff ssDNA genome and single
      stranded polynucleotides. Its affinity, K omega (the intrinsic binding constant
      times a cooperativity factor), can differ by several orders of magnitude for
      ssDNAs of different nearest-neighbor base compositions [Mou, T. C., Gray, C. W.,
      and Gray, D. M. (1999) Biophys. J. 76, 1537-1551]. We found that the DNA backbone
      can also dramatically affect the binding affinity. The K omega for binding
      phosphorothioate-modified S-d(A)(36) was >300-fold higher than for binding
      unmodified P-d(A)(36) at 0.2 M NaCl. CD titrations showed that g5p bound
      phosphorothioate-modified oligomers with the same stoichiometry as unmodified
      oligomers. The CD spectrum of S-d(A)(36) underwent the same qualitative change
      upon protein binding as did the spectrum of unmodified DNA, and the
      phosphorothioate-modified DNA appeared to bind in the normal g5p binding site.
      Oligomers of d(A)(36) with different proportions of phosphorothioate nucleotides
      had binding affinities and CD perturbations intermediate to those of the fully
      modified and unmodified sequences. The influence of phosphorothioation on binding
      affinity was nearly proportional to the extent of the modification, with a small
      nearest-neighbor dependence. These and other results using d(ACC)(12) oligomers
      and mutant proteins indicated that the increased binding affinity of g5p for
      phosphorothioate DNA was not a polyelectrolyte effect and probably was not an
      effect due to the altered nucleic acid structure, but was more likely a general
      effect of the properties of the sulfur in the context of the phosphorothioate
      group.

PMID- 11329297
TI  - Escherichia coli transcription termination factor Rho binds and hydrolyzes ATP
      using a single class of three sites.
AB  - Escherichia coli transcription termination factor Rho uses the energy of ATP
      hydrolysis to travel 5' --> 3' along RNA. We previously showed that the hexameric
      Rho protein binds three molecules of ATP in active sites and that hydrolysis of
      the three bound ATP molecules upon RNA binding is sequential. Other models of Rho
      ATP hydrolysis activity have arisen from reports of additional ATP binding sites
      on Rho. Here we present further evidence from binding, isotope partitioning, and
      rapid mix/chemical quench experiments, in support of the presence of only three
      equivalent ATP binding sites on Rho that are catalytic sites and that fire
      sequentially. These results are incorporated into a proposed mechanism for
      directional Rho tracking along RNA.

PMID- 11329298
TI  - Effects of benzo[a]pyrene DNA adducts on Escherichia coli DNA polymerase I
      (Klenow fragment) primer-template interactions: evidence for inhibition of the
      catalytically active ternary complex formation.
AB  - Benzo[a]pyrene diol epoxide (B[a]PDE) adducts are strong blocks of DNA
      replication in vitro, allowing the rare incorporation of a nucleotide across from
      the lesion and negligibly small extent of further bypass. To study the
      mechanistic details of this process, a gel-retardation assay was used to measure
      the dissociation constants for the binding of DNA polymerase I (Klenow fragment)
      (KF) to the primer-templates containing a (+)-trans- or (+)-cis-B[a]P-N(2)-dG
      adduct. When the primer was terminated one nucleotide before the adduct, the
      presence of a (+)-trans-B[a]P-N(2)-dG adduct did not affect the binding while a
      (+)-cis-B[a]P-N(2)-dG adduct caused a slight decrease in affinity. The presence
      of any dNTP decreased the affinity of KF to the modified primer-templates. (In
      contrast, a strong increase of the affinity to unmodified primer-templates was
      observed in the presence of the next correct dNTP.) Limited protease digestion
      experiments indicated that a closed ternary complex of KF with the modified
      primer-templates was not detectable in the presence of any dNTP, whereas it was
      clearly observed with unmodified template in the presence of the next correct
      nucleotide. These findings suggest that these adducts may interfere with the
      conformational change to the catalytically active closed ternary complex and/or
      cause significant destabilization of this complex. When the primers extended to
      the position across from the adduct, the affinity of KF was significantly
      decreased irrespective of the identity of the base across from the adduct,
      possibly explaining the low bypass of the lesion. Interestingly, the stability of
      these DNA-polymerase complexes correlated with nucleotide insertion kinetics for
      the unmodified and (+)-trans-B[a]PDE-modified templates.

PMID- 11329299
TI  - Importance of specific nucleotides in the folding of the natural form of the
      hairpin ribozyme.
AB  - The hairpin ribozyme in its natural context consists of two loops in RNA duplexes
      that are connected as arms of a four-way helical junction. Magnesium ions induce
      folding into the active conformation in which the two loops are in proximity. In
      this study, we have investigated nucleotides that are important to this folding
      process. We have analyzed the folding in terms of the cooperativity and apparent
      affinity for magnesium ions as a function of changes in base sequence and
      functional groups, using fluorescence resonance energy transfer. Our results
      suggest that the interaction between the loops is the sum of a number of
      component interactions. Some sequence variants such as A10U, G+1A, and C25U
      exhibit loss of cooperativity and reduced affinity of apparent magnesium ion
      binding. These variants are also very impaired in ribozyme cleavage activity.
      Nucleotides A10, G+1, and C25 thus appear to be essential in creating the
      conformational environment necessary for ion binding. The double variant
      G+1A/C25U exhibits a marked recovery of both folding and catalytic activity
      compared to either individual variant, consistent with the proposal of a triple
      base interaction among A9, G+1, and C25 [Pinard, R., Lambert, D., Walter, N. G.,
      Heckman, J. E., Major, F., and Burke, J. M. (1999) Biochemistry 38, 16035-16039].
      However, substitution of A9 leads to relatively small changes in folding
      properties and cleavage activity, and the double variant G+1DAP/C25U (DAP is 2,6
      diaminopurine), which could form an isosteric triple-base interaction, exhibits
      folding and cleavage activities that are both very impaired compared to those of
      the natural sequence. Our results indicate an important role for a Watson--Crick
      base pair between G+1 and C25; this may be buttressed by an interaction with A9,
      but the loss of this has less significant consequences for folding. 2'
      Deoxyribose substitution leads to folding with reduced magnesium ion affinity in
      the following order: unmodified RNA > dA9 > dA10 > dC25 approximately dA10 plus
      dC25. The results are interpreted in terms of an interaction between the ribose
      ring of C25 and the ribose and base of A10, in agreement with the proposal of
      Ryder and Strobel [Ryder, S. P., and Strobel, S. A. (1999) J. Mol. Biol. 291, 295
      311]. In general, there is a correlation between the ability to undergo ion
      induced folding and the rate of ribozyme cleavage. An exception to this is
      provided by G8, for which substitution with uridine leads to severe impairment of
      cleavage but folding characteristics that are virtually unaltered from those of
      the natural species. This is consistent with a direct role for the nucleobase of
      G8 in the chemistry of cleavage.

PMID- 11329301
TI  - D1-Asp170 is structurally coupled to the oxygen evolving complex in photosystem
      II as revealed by light-induced Fourier transform infrared difference
      spectroscopy.
AB  - We report both mid-frequency (1800-1200 cm(-)(1)) and low-frequency (670-350 cm(
      )(1)) S(2)/S(1) FTIR difference spectra of photosystem II (PSII) particles
      isolated from wild-type and D1-D170H mutant cells of the cyanobacterium
      Synechocystis sp. PCC 6803. Both mid- and low-frequency S(2)/S(1) spectra of the
      Synechocystis wild-type PSII particles closely resemble those from spinach PSII
      samples, which confirms an earlier result by Noguchi and co-workers [Noguchi, T.,
      Inoue, Y., and Tang, X.-S. (1997) Biochemistry 36, 14705-14711] and indicates
      that the coordination environment of the oxygen evolving complex (OEC) in
      Synechocystis is very similar to that in spinach. We also found that there is no
      appreciable difference between the mid-frequency S(2)/S(1) spectra of wild-type
      and of D1-D170H mutant PSII particles, from which we conclude that D1-Asp170 does
      not undergo a significant structural change during the S(1) to S(2) transition.
      This result also suggests that, if D1-Asp170 ligates Mn, it does not ligate the
      Mn ion that is oxidized during the S(1) to S(2) state transition. Finally, we
      found that a mode at 606 cm(-)(1) in the low-frequency wild-type S(2)/S(1)
      spectrum shifts to 612 cm(-)(1) in the D1-D170H mutant spectrum. Because this 606
      cm(-)(1) mode has been previously assigned to an Mn-O-Mn cluster mode of the OEC
      [Chu, H.-A., Sackett, H., and Babcock, G. T. (2000) Biochemistry 39, 14371
      14376], we conclude that D1-Asp170 is structurally coupled to the Mn-O-Mn cluster
      structure that gives rise to this band. Our results suggest that D1-Asp170 either
      directly ligates Mn or Ca(2+) or participates in a hydrogen bond to the
      Mn(4)Ca(2+) cluster. Our results demonstrate that combining FTIR difference
      spectroscopy with site-directed mutagenesis has the potential to provide insights
      into structural changes in Mn and Ca(2+) coordination environments in the
      different S states of the OEC.

PMID- 11329300
TI  - Probes of hydrogen tunneling with horse liver alcohol dehydrogenase at subzero
      temperatures.
AB  - The temperature dependence of steady-state kinetics has been studied with horse
      liver alcohol dehydrogenase (HLADH) using protonated and deuterated benzyl
      alcohol as substrates in methanol/water mixtures between +3 and -50 degrees C.
      Additionally, the competitive isotope effects, k(H)/k(T) and k(D)/k(T), were
      measured. The studies indicate increasing kinetic complexity for wild-type HLADH
      at subzero temperatures. Consistent with earlier findings at 25 degrees C
      [Bahnson et al. (1993) Biochemistry 31, 5503], the F93W mutant shows much less
      kinetic complexity than the wild-type enzyme between 3 and -35 degrees C. An
      analysis of noncompetitive deuterium isotope effects and competitive tritium
      isotope effects leads to the conclusion that the reaction of F93W involves
      substantial hydrogen tunneling down to -35 degrees C. The effect of methanol on
      kinetic properties for the F93W mutant was analyzed, showing a dependence of
      competitive KIEs on the NAD(+) concentration. This indicates a more random bi--bi
      kinetic mechanism, in comparison to an ordered bi-bi kinetic mechanism in water.
      Although MeOH also affects the magnitude of the reaction rates and, to some
      extent, the observed KIEs, the ratio of ln k(H)/k(T) to ln k(D)/k(T) for primary
      isotope effects has not changed in methanol, and we conclude little or no change
      in kinetic complexity. Importantly, the degree of tunneling, as shown from the
      relationship between the secondary k(H)/k(T) and k(D)/k(T) values, is the same in
      water and MeOH/water mixtures, implicating similar trajectories for H transfer in
      both solvents. In a recent study of a thermophilic alcohol dehydrogenase [Kohen
      et al. (1999) Nature 399, 496], it was shown that decreases in temperatures below
      a transition temperature lead to decreased tunneling. This arises because of a
      change in protein dynamics below a break point in enzyme activity [Kohen et al.
      (2000) J. Am. Chem. Soc. 122, 10738-10739]. For the mesophilic HLADH described
      herein, an opposite trend is observed in which tunneling increases at subzero
      temperatures. These differences are attributed to inherent differences in
      tunneling probabilities between 0 and 100 degrees C vs subzero temperatures, as
      opposed to fundamental differences in protein structure for enzymes from
      mesophilic vs thermophilic sources. We propose that future investigations of the
      relationship between protein flexibility and hydrogen tunneling are best
      approached using enzymes from thermophilic sources.

PMID- 11329302
TI  - Tractable approximations for probabilistic models: the adaptive Thouless-Anderson
      Palmer mean field approach.
AB  - We develop an advanced mean field method for approximating averages in
      probabilistic data models that is based on the Thouless-Anderson-Palmer (TAP)
      approach of disorder physics. In contrast to conventional TAP, where the
      knowledge of the distribution of couplings between the random variables is
      required, our method adapts to the concrete couplings. We demonstrate the
      validity of our approach, which is so far restricted to models with nonglassy
      behavior, by replica calculations for a wide class of models as well as by
      simulations for a real data set.

PMID- 11329303
TI  - Spatial persistence of fluctuating interfaces.
AB  - We show that the probability, P0(l), that the height of a fluctuating (d+1)
      dimensional interface in its steady state stays above its initial value up to a
      distance l, along any linear cut in the d-dimensional space, decays as P0(l)
      approximately l(theta). Here straight theta is a "spatial" persistence exponent,
      and takes different values, straight theta(s) or straight theta(0), depending on
      how the point from which l is measured is specified. These exponents are shown to
      map onto corresponding temporal persistence exponents for a generalized d = 1
      random-walk equation. The exponent straight theta(0) is nontrivial even for
      Gaussian interfaces.

PMID- 11329304
TI  - Rotating hairy black holes.
AB  - We construct stationary black-hole solutions in SU(2) Einstein-Yang-Mills theory
      which carry angular momentum and electric charge. Possessing nontrivial non
      Abelian magnetic fields outside their regular event horizon, they represent
      nonperturbative rotating hairy black holes.

PMID- 11329305
TI  - Domain walls without cosmological constant in higher order gravity.
AB  - We consider a class of higher order corrections in the form of Euler densities of
      arbitrary rank n to the standard gravity action in D dimensions. We present a
      generating functional and an explicit form of the conserved energy-momentum
      tensors. We show that this class of corrections allows for domain-wall solutions
      despite the presence of higher powers of the curvature. The existence of such
      solutions no longer depends on the presence of cosmological constants. For
      example, the Randall-Sundrum-type scenario can be realized without bulk and/or
      brane cosmological constant.

PMID- 11329308
TI  - Counting inclusive b jets as an efficient probe of new flavor physics.
AB  - We consider the inclusive reaction l(+)l(-)-->nb+X ( n = number of b jets) in
      lepton colliders for which we propose a useful approximately conserved quantum
      number b(P) = (-1)(n) that we call b parity ( b(P)). We make the observation that
      the standard model (SM) is essentially b(P) even since SM b(P)-violating signals
      are necessarily Cabibbo-Kobayashi-Maskawa suppressed. In contrast new flavor
      physics can produce b(P) = -1 signals whose only significant SM background is due
      to b-jet misidentification. Thus, we show that b-jet counting, that relies
      primarily on b tagging, becomes a very simple and sensitive probe of new flavor
      physics (i.e., of b(P) violation).

PMID- 11329309
TI  - Measuring the top Yukawa coupling to a heavy Higgs Boson at future e(+)e(-)
      linear colliders.
AB  - If the Higgs boson mass is greater than 350 GeV, the top quark Yukawa coupling
      can be determined using the Higgs resonant contribution to t&tmacr; production
      from W+W- fusion at high energy e(+)e(-) linear colliders. We have evaluated the
      significance with which the signal of a Higgs decaying to t&tmacr; pairs could be
      observed at future e(+)e(-) colliders, with center of mass energies of 800 GeV
      and 1 TeV, and an integrated luminosity of 1 ab(-1). We find that a signal
      significance greater than 5sigma and a relative error in the top Yukawa
      measurement better than 10% can be achieved at these facilities, for Higgs boson
      masses in the ranges of 350-500 GeV and 350-650 GeV, respectively.

PMID- 11329311
TI  - Electromagnetic moments of the beta-emitting nucleus 16N.
AB  - The nuclear magnetic dipole moment mu and electric quadrupole moment Q of the
      beta-emitting 16N(Ipi = 2(-), T(1/2) = 7.13 s) nucleus have been determined for
      the first time by detecting its beta-NMR in a MgO crystal and beta-NQR (nuclear
      quadrupole resonance) in a TiO (2) crystal to be /mu/ = (1.9859+/-0.0011) mu(N)
      and /Q/ = (17.9+/-1.7) mb, respectively. Although the prediction of mu given by
      the Hartree-Fock calculation agrees well with the experiment, an abnormally small
      effective charge for neutrons is required to account for the experimental Q.

PMID- 11329307
TI  - Observation of B --> phiK and B --> phiK*.
AB  - We have studied two-body charmless hadronic decays of B mesons into the final
      states straight phiK and phiK(*). Using 9.7 million B&Bmacr; pairs collected with
      the CLEO II detector, we observe the decays B- --> phiK- and B0--> phiK(*0) with
      the following branching fractions: B(B--->phiK-) = (5.5(+2.1)(-1.8)+/-0.6)x10(-6)
      and B(B0--> phiK(*0)) = (11.5(+4.5+1.8)(-3.7-1.7))x10(-6). We also see evidence
      for the decays B0-->phiK0 and B---> phiK(*-). However, since the statistical
      significance is not overwhelming for these modes, we determine upper limits of
      <12.3x10(-6) and <22.5x10(-6) ( 90% confidence level), respectively.

PMID- 11329312
TI  - The A(y) problem for p-3He elastic scattering.
AB  - We present evidence that numerically accurate quantum calculations employing
      modern internucleon forces do not reproduce the proton analyzing power, A(y), for
      p- 3He elastic scattering at low energies. These calculations underpredict new
      measured analyzing powers by approximately 30% at E(c.m.) = 1.20 MeV and by 40%
      at E(c.m.) = 1.69 MeV, an effect analogous to a well-known problem in p-d and n-d
      scattering. The calculations are performed using the complex Kohn variational
      principle and the (correlated) hyperspherical harmonics technique with full
      treatment of the Coulomb force. The inclusion of the three-nucleon interaction
      does not improve the agreement with the experimental data.

PMID- 11329310
TI  - Observation of the Omega(0)(c) Charmed Baryon at CLEO.
AB  - The CLEO experiment at the CESR collider has used 13.7 fb(-1) of data to search
      for the production of the Omega(0)(c) (css ground state) in e(+)e(-) collisions
      at square root of (s) approximately 10.6 GeV. The modes used to study the
      Omega(0)(c) are Omega(-)pi(+), Omega(-)pi(+)pi(0), Xi-K-pi(+)pi(+), Xi0K-pi(+),
      and Omega(-)pi(+)pi(+)pi(-). We observe a signal of 40.4+/-9.0(stat) events at a
      mass of 2694.6+/-2.6(stat)+/-1.9(syst) MeV/c(2), for all modes combined.

PMID- 11329313
TI  - Collisional frequency shifts in 133Cs fountain clocks.
AB  - We present a theoretical analysis of the density dependent frequency shift in Cs
      fountain clocks using the highly constrained binary collision model described by
      Leo et al. [Phys. Rev. Lett. 85, 2721 (2000)]. We predict a reversal in the clock
      shift at temperatures near 0.08 microK. Our results show that s waves dominate
      the collision process. However, as a consequence of the large scattering lengths
      in Cs the clock shift is strongly temperature dependent and does not reach a
      constant Wigner-law value until temperatures are less than 0.1 nK.

PMID- 11329314
TI  - Statistical properties of inter-series mixing in helium: from integrability to
      chaos.
AB  - The photoionization spectrum of helium shows considerable complexity close to the
      double-ionization threshold. By analyzing the results from both our recent
      experiments and ab initio three- and one-dimensional calculations, we show that
      the statistical properties of the spacings between neighboring energy levels
      clearly display a transition towards quantum chaos.

PMID- 11329315
TI  - Total, partial, and electron-capture cross sections for ionization of water vapor
      by 20-150 keV protons.
AB  - We present experimental results for proton ionization of water molecules based on
      a novel event by event analysis of the different ions produced (and lost). We are
      able to obtain mass analyzed product ion signals (e.g., H2O+, OH+, O+, O++, H+)
      in coincidence with the projectile analyzed after the collision, i.e., either
      being H+, neutral H after single electron capture during the ionization event, or
      H- after double electron capture. After proper calibration we are thus able to
      determine a complete set of cross sections for the ionization of a molecular
      target by protons including the total and the partial cross sections and in
      addition also the direct ionization and the electron capture cross sections.

PMID- 11329316
TI  - Double ionization of helium by electron-impact: complete pictures of the four
      body breakup dynamics.
AB  - The dynamics of He double ionization by 2 keV electron impact is studied
      experimentally for a momentum transfer of 0.6 a.u. at excess energies of 10 and
      40 eV. Complete sets of fivefold differential cross sections are presented for
      all electron emission angles in coplanar geometry. Contributions beyond the first
      Born approximation are identified comparing experimental data with first order
      convergent close-coupling calculations which are in considerably better agreement
      with the present experiment than with the earlier measurement of Kheifets et al.
      [J. Phys. B 32, 5047 (1999)].

PMID- 11329317
TI  - Formation of Rydberg atoms in an expanding ultracold neutral plasma.
AB  - We study the formation of Rydberg atoms in expanding plasmas at temperatures of 1
      1000 K and densities from 10(5)-10(10) cm(-3). Up to 20% of the initially free
      charges recombine in about 100 micros, and the binding energy of the Rydberg
      atoms approximately equals the increase in the kinetic energy of the remaining
      free electrons. Three-body recombination is expected to dominate in this regime,
      yet most of our results are inconsistent with this mechanism.

PMID- 11329319
TI  - Dynamic stabilization in 1sigma(u)-->1pi(g) excited nitrogen clusters.
AB  - High-resolution 1s near-edge spectra of molecular nitrogen and variable size
      nitrogen clusters obtained using monochromatic synchrotron radiation from the
      high brilliance BESSY-II storage ring facility are reported. The vibrationally
      resolved 1sigma(u)-->1pi(g) core-to-valence excitation band of clusters shows a
      distinct redshift of 6+/-1 meV relative to the isolated molecule, but the
      vibrational structure and linewidths are essentially unchanged. This shift is
      assigned to dynamic stabilization of 1sigma(u)-->1pi(g) excited molecules in
      clusters, arising from the dynamic dipole moment generated by core-hole
      localization in the low-symmetry cluster field. This leads to changes in
      intermolecular interactions compared to the ground-state cluster. Such spectral
      shifts are expected to occur generally in molecular clusters and in the
      corresponding condensed phase.

PMID- 11329318
TI  - Measurement of the resonant d(mu)t molecular formation rate in solid HD.
AB  - Measurements of muon-catalyzed dt fusion ( d(mu)t-->4He + n + mu(-)) in solid HD
      have been performed. The theory describing the energy dependent resonant
      molecular formation rate for the reaction (mu)t + HD-->[(d(mu)t)pee](*) is
      compared to experimental results in a pure solid HD target. Constraints on the
      rates are inferred through the use of a Monte Carlo model developed specifically
      for the experiment. From the time-of-flight analysis of fusion events in 16 and
      37 microg x cm(-2) targets, an average formation rate consistent with 0.897+/
      (0.046)(stat)+/-(0.166)(syst) times the theoretical prediction was obtained.

PMID- 11329320
TI  - Self-organization in granular slurries.
AB  - We report the existence of self-organization in wet granular media or slurries,
      mixtures of particles of different sizes dispersed in a lower density liquid. As
      in the case of dry granular mixtures, axial banding (alternating bands rich in
      small and large particles in a long rotating cylinder) and radial segregation (in
      quasi-2D containers) are observed in slurries. However, when compared with the
      dry counterpart axial segregation is significantly faster and the spectrum of
      outcomes is richer. Moreover, experiments with suitable fluids reveal, for the
      first time, the internal structure of axially segregated systems, something that
      up to now has been accessible only via magnetic resonance imaging
      experimentation.

PMID- 11329306
TI  - Quasi-model-independent search for new high p(T) physics at D0.
AB  - We apply a quasi-model-independent strategy ("Sleuth") to search for new high
      p(T) physics in approximately 100 pb(-1) of pp collisions at square root of (s) =
      1.8 TeV collected by the D0 experiment during 1992-1996 at the Fermilab Tevatron.
      We systematically analyze many exclusive final states and demonstrate sensitivity
      to a variety of models predicting new phenomena at the electroweak scale. No
      evidence of new high p(T) physics is observed.

PMID- 11329321
TI  - Pressure spectrum in homogeneous turbulence.
AB  - The pressure spectrum in homogeneous steady turbulence is studied using direct
      numerical simulation with resolution up to 1024(3) and the Reynolds number
      R(lambda) between 38 and 478. The energy spectrum is found to have a finite
      inertial range with the Kolmogorov constant K = 1.65+/-0.05 followed by a bump at
      large wave numbers. The pressure spectrum in the inertial range is found to be
      approximately P(k) = B(p)epsilon;(4/3)k(-7/3) with B(p) = 8.0+/-0.5, and followed
      by a bump of nearly k(-5/3) at higher wave numbers. Universality and a new
      scaling of the pressure spectrum are discussed.

PMID- 11329322
TI  - Novel final focus design for future linear colliders.
AB  - The length, complexity, and cost of the present final focus designs for linear
      colliders grow very quickly with the beam energy. In this Letter, a novel final
      focus system is presented and compared with the one proposed for the Next Linear
      Collider (NLC Zeroth-Order Design Report, edited by T. O. Raubenheimer, SLAC
      Report No. 474, 1996). This new design has fewer optical elements and is much
      shorter, nonetheless achieving better chromatic properties. Moreover, the new
      system is more suitable for operation over a larger energy range.

PMID- 11329323
TI  - Doppler-shifted cyclotron absorption of electron Bernstein waves via N( parallel)
      upshift in a Tokamak plasma.
AB  - Extraordinary (X) waves are perpendicularly injected for electron Bernstein (B)
      wave heating into an Ohmically heated plasma from the inboard side in the WT-3
      tokamak. Measurements show that absorption does not take place at the electron
      cyclotron resonance layer nor the upper hybrid resonance layer, but does happen
      midway between them. This is consistent with the ray tracing prediction, i.e.,
      the poloidal field and poloidal inhomogeneity of toroidal field lead the B waves
      to have a large parallel refractive index N( parallel) (>1), and the B waves are
      damped away via the Doppler-shifted cyclotron resonance.

PMID- 11329324
TI  - Alternative mechanism for omega(0)/2 emission in laser-produced plasmas.
AB  - Several models have been proposed to explain the broad spectral features
      characteristic of omega(0)/2 emission observed in laser-produced plasmas. In this
      article, the electromagnetic decay instability is examined as an alternative
      explanation for this emission. It is shown that the electromagnetic decay
      instability is able to explain some of the spectral features observed from laser
      produced plasmas. In addition, the electromagnetic decay instability is
      consistent with two other features observed in experiments: the efficient
      generation of electromagnetic energy and the discrepancy in the levels of
      emission between the omega(0)/2 emission and the 3omega(0)/2 emission.

PMID- 11329325
TI  - Structural investigations on smectic blue phases.
AB  - Smectic blue phases ( BP(Sm)) are thermotropic liquid crystalline phases which
      exhibit both three-dimensional orientational order, such as classical blue
      phases, and smectic positional order. BP(Sm) appear as the three-dimensional
      counterpart of twist grain boundary phases. X-ray scattering and optical
      polarizing microscopy provide information on the hexagonal and cubic symmetries
      of these new phases.

PMID- 11329326
TI  - New source of stacking faults in heteroepitaxial systems.
AB  - A new stacking fault formation mechanism has been observed for the first time in
      ZnO/LiTaO(3) heteroepitaxial films. High resolution electron microscopy studies
      combined with electron diffraction and numerical image computation suggest that
      the observed type I1 intrinsic stacking faults in an epitaxial film can be
      dominantly formed as a result of tilting of the lattices between films and
      substrate required to maintain a particular orientation relationship.

PMID- 11329327
TI  - X-ray studies of phonon softening in tise2.
AB  - The charge-density-wave transition in TiSe (2), which results in a commensurate
      (2x2x2) superlattice at temperatures below approximately 200 K, presumably
      involves softening of a zone-boundary phonon mode. For the first time, this
      phonon-softening behavior has been examined over a wide temperature range by
      synchrotron x-ray thermal diffuse scattering.

PMID- 11329328
TI  - Sound wave scattering in network glasses.
AB  - The acoustic branch of two network glasses, (Li2O)xB2O3 ( x = 0.25 and 0.5), is
      followed over a large momentum transfer range 1-12 nm(-1), using inelastic x-ray
      scattering. We observe the transition from propagating modes to a region of
      strong scattering as the Ioffe-Regel limit is reached. A region of Rayleigh
      scattering of the acoustic modes precedes the strong scattering regime at larger
      Q, causing a rapid decrease of the mean-free path of the modes.

PMID- 11329329
TI  - Direct observation of capillary condensation of a solid.
AB  - We describe the direct condensation of a solid from vapor in an annular mica
      wedge. Neo-pentanol initially condenses as a liquid from 8 to 57 degrees C (the
      melting point T(m)), followed by nucleation of a solid from vapor for T<45
      degrees C. Menthol (T(m) = 42 degrees C) gives only liquid condensates down to 12
      degrees C. The adsorbed films of neo-pentanol, which unlike those of menthol show
      layering transitions, and the disordered crystalline phase of bulk neo-pentanol
      appear to facilitate condensation of the solid phase. There is evidence for a
      change in the nature of the solid neo-pentanol condensate with T.

PMID- 11329331
TI  - GaAs(2 5 11): a new stable surface within the stereographic triangle.
AB  - The atomic structure of GaAs(2 5 11), a hitherto unknown stable surface, has been
      determined by in situ scanning tunneling microscopy and first-principles
      electronic structure calculations. This orientation is located within the
      stereographic triangle, i.e., far away from all low-index surfaces. A low-energy
      ( 1x1) reconstruction containing arsenic dimers forms on the surface. The
      analysis of the surface structure shows that, for semiconductor surfaces, the
      gain in stability due to minimization of the number of dangling bonds is more
      important than the gain from rendering a semiconducting ground state.

PMID- 11329330
TI  - Stability of polar oxide surfaces.
AB  - The structures of the polar surfaces of ZnO are studied using ab initio
      calculations and surface x-ray diffraction. The experimental and theoretical
      relaxations are in good agreement. The polar surfaces are shown to be very
      stable; the cleavage energy for the (0001)-Zn and (0001;)-O surfaces is 4.0
      J/m(2) comparable to 2.32 J/m(2) for the most stable nonpolar (1010) surface. The
      surfaces are stabilized by an electronic mechanism involving the transfer of 0.17
      electrons between them. This leads to 2D metallic surface states, which has
      implications for the use of the material in gas sensing and catalytic
      applications.

PMID- 11329332
TI  - Direct observation of misfit dislocation glide on surfaces.
AB  - Using scanning tunneling microscopy we have observed thermally induced
      dislocation glide in monolayer Cu films on Ru(0001) at room temperature. The
      motion is governed by a Peierls barrier that depends on the detailed structure of
      the dislocations, in particular upon whether the threading dislocations that
      terminate them are dissociated or not. Calculations based on the Frenkel
      Kontorova model reproduce the threading dislocation structure and provide
      estimates of the Peierls barrier and dislocation stiffness which are consistent
      with experiment.

PMID- 11329333
TI  - Jahn-Teller phonon anomaly and dynamic phase fluctuations in La0.7Ca0.3MnO3.
AB  - Inelastic neutron scattering was used to study the temperature (T) dependence of
      the lattice excitations in La 0.7Ca 0.3MnO (3). An optical Jahn-Teller phonon
      exhibits continuous but anomalous damping with increasing temperature in the
      ferromagnetic-metallic phase and collapses above the Curie temperature T(C) (240
      K). We attribute this anomaly to the growing dynamic phase segregation as T-
      >T(C), thus providing evidence of local fluctuations associated with the short
      range polaron or charge/orbital ordering in the ferromagnetic-metallic state.

PMID- 11329334
TI  - Nanostructured copper filaments in electrochemical deposition.
AB  - In this Letter we report a novel self-organized copper electrodeposition in an
      ultrathin layer of CuSO4 electrolyte. The macroscopic fingering branches of the
      deposit consist of long copper filaments covered with periodic corrugated
      nanostructures. The mechanism of the nanostructure formation is explored and the
      origin of the significant descent of the branching rate in electrodeposition is
      discussed. We suggest that this growth phenomenon provides deeper insights into
      the role of diffusion and migration on pattern formation in electrodeposition.

PMID- 11329335
TI  - Metal-insulator crossover in superconducting cuprates in strong magnetic fields.
AB  - The metal-insulator crossover of the in-plane resistivity upon temperature
      decrease, recently observed in several classes of cuprate superconductors, when a
      strong magnetic field suppresses the superconductivity, is explained using the
      U(1)xSU(2) Chern-Simons gauge field theory. The origin of this crossover is the
      same as that for a similar phenomenon observed in heavily underdoped cuprates
      without magnetic field. It is due to the interplay between the diffusive motion
      of the charge carriers and the "peculiar" localization effect due to short-range
      antiferromagnetic order. We also calculate the in-plane transverse
      magnetoresistance which is in fairly good agreement with available experimental
      data.

PMID- 11329336
TI  - Energetics and electronic structures of encapsulated C60 in a carbon nanotube.
AB  - We report total-energy electronic structure calculations that provide energetics
      of encapsulation of C60 in the carbon nanotube and electronic structures of the
      resulting carbon peapods. We find that the encapsulating process is exothermic
      for the (10,10) nanotube, whereas the processes are endothermic for the (8,8) and
      (9,9) nanotubes, indicative that the minimum radius of the nanotube for the
      encapsulation is 6.4 A. We also find that the C(60)@(10,10) is a metal with
      multicarriers each of which distributes either along the nanotube or on the C60
      chain. This unusual feature is due to the nearly free electron state that is
      inherent to hierarchical solids with sufficient space inside.

PMID- 11329337
TI  - Bose-Einstein condensation quantum kinetics for a gas of interacting excitons.
AB  - A quantum kinetics of the Bose-Einstein condensation in the self-consistent
      (s.c.) Hartree-Fock-Bogoliubov (HFB) model of the interacting Bose gas is
      formulated and numerically solved for the example of excitons scattering with a
      thermal bath of acoustic phonons. The theory describes the condensation in real
      time starting from a nonequilibrium initial state towards the equilibrium HFB
      solution. The s.c. changes of the spectrum are automatically incorporated in the
      scattering terms.

PMID- 11329338
TI  - Universal crossover from band to hopping conduction in molecular organic
      semiconductors.
AB  - The charge transport in a variety of herringbone-stacked organic molecular
      semiconductors is investigated in the temperature range from 10 to 550 K. A
      crossover from coherent bandlike charge transport with mobilities up to several
      thousand cm (2)/V s at low temperature to an incoherent hopping motion at high
      temperatures is observed. This is attributed to the localization of the charge
      carrier due to increased electron-phonon interaction and, finally, the formation
      of a lattice polaron.

PMID- 11329339
TI  - Prediction of a surface state and a related surface insulator-metal transition
      for the (100) surface of stochiometric EuO.
AB  - We calculate the temperature and layer-dependent electronic structure of a 20
      layer EuO(100) film using a combination of first-principles and model calculation
      based on the ferromagnetic Kondo-lattice model. The results suggest the existence
      of a EuO(100) surface state which can lead to a surface insulator-metal
      transition.

PMID- 11329340
TI  - Wigner crystallization in mesoscopic 2d electron systems.
AB  - Wigner crystallization of electrons in 2D quantum dots is reported. It proceeds
      in two stages: (i) via radial ordering of electrons on shells and (ii) freezing
      of the intershell rotation. The phase boundary of the crystal is computed in the
      whole temperature-density plane, and the influences of quantum effects and the
      particle number are analyzed.

PMID- 11329341
TI  - Coherence and partial coherence in interacting electron systems.
AB  - We study coherence of electron transport through interacting quantum dots and
      discuss the relation of the coherent part to the flux-sensitive conductance for
      three different types of Aharonov-Bohm interferometers. Contributions to
      transport in first and second order in the intrinsic linewidth of the dot levels
      are addressed in detail. We predict an asymmetry of the interference signal
      around resonance peaks as a consequence of incoherence associated with spin-flip
      processes. Furthermore, we show by strict calculation that first-order
      contributions can be partially or even fully coherent. This contrasts with the
      sequential-tunneling picture which describes first-order transport as a sequence
      of incoherent processes.

PMID- 11329342
TI  - Towards a chemically driven molecular electron pump.
AB  - Charge can be pumped through a tiny gated portal from a reservoir at low
      electrochemical potential to one at the same or higher electrochemical potential
      by cyclically modulating the portal and gate energies. A theoretically and
      experimentally well established mechanism is Thouless adiabatic pumping, achieved
      by a precisely timed out-of-phase modulation of at least two parameters of the
      system. Here we show that stochastic modulation between two configurations of
      gate and portal energies can drive efficient pumping by a different,
      nonadiabatic, mechanism that may provide a basis for chemically driven electron
      pumping through a molecular wire.

PMID- 11329343
TI  - Levitation of current carrying states in the lattice model for the integer
      quantum Hall effect.
AB  - The disorder driven quantum Hall to insulator transition is investigated for a
      two-dimensional lattice model. The Hall conductivity and the localization length
      are calculated numerically near the transition. For uncorrelated and weakly
      correlated disorder potentials the current carrying states are annihilated by the
      negative Chern states originating from the band center. In the presence of
      correlated disorder potentials with correlation length larger than approximately
      half the lattice constant the floating up of the critical states in energy
      without merging is observed. This behavior is similar to the levitation scenario
      proposed for the continuum model.

PMID- 11329344
TI  - Mobility-dependent charge injection into an organic semiconductor.
AB  - Measurements of charge injection from indium tin oxide (ITO) into the organic
      semiconductor, tetraphenyl diamine doped polycarbonate (PC:TPD), were carried
      out. The current injected at the contact was measured as a function of the hole
      mobility in the organic semiconductor, which was varied from 10(-6) to 10(-3) cm
      (2)/V x s by adjusting the concentration of the hole transport agent, TPD, in the
      PC host. These experiments reveal that the current injected at the contact is
      proportional to the hole mobility in the bulk. As a result, the ITO/PC:TPD
      contact is found to limit current flow in all samples, regardless of the hole
      mobility in PC:TPD.

PMID- 11329345
TI  - Electron spectral function and algebraic spin liquid for the normal state of
      underdoped high T(c) superconductors.
AB  - We propose to describe the spin fluctuations in the normal state (spin-pseudogap
      phase) of underdoped high T(c) cuprates as a manifestation of an algebraic spin
      liquid. Within the slave boson implementation of spin-charge separation, the
      normal state is described by massless Dirac fermions, charged bosons, and a gauge
      field. The gauge interaction, as an exact marginal perturbation, drives the mean
      field free-spinon fixed point to a new spin-quantum fixed point-the algebraic
      spin liquid. Luttinger-liquid-like line shapes for the electron spectral function
      are obtained in the normal state, and we show how a coherent quasiparticle peak
      appears as spin and charge recombine.

PMID- 11329346
TI  - Observability of quantum phase fluctuations in cuprate superconductors.
AB  - We study the order parameter phase fluctuation effects in cuprate superconductors
      near T = 0, using a quasi-two-dimensional d-wave BCS model. An effective phason
      theory is obtained which is used to estimate the strength of the fluctuations,
      the fluctuation correction to the in-plane penetration depth, and the pair-field
      susceptibility. We find that, while the phase fluctuation effects are difficult
      to observe in the renormalization of the superfluid phase stiffness, they may be
      observed in a pair tunneling experiment which measures the pair-field
      susceptibility.

PMID- 11329347
TI  - Spin order due to orbital fluctuations: cubic vanadates.
AB  - We investigate the highly frustrated spin and orbital superexchange interactions
      in cubic vanadates. The fluctuations of t(2g) orbitals trigger a novel mechanism
      of ferromagnetic interactions between spins S = 1 of V3+ ions along one of the
      cubic directions which operates already in the absence of Hund's rule exchange
      J(H), and leads to the C-type antiferromagnetic phase in LaVO3. The Jahn-Teller
      effect can stabilize the orbital ordering and the G-type antiferromagnetic phase
      at low temperatures, but large entropy due to orbital fluctuations favors again
      the C phase at higher temperatures, as observed in YVO (3).

PMID- 11329348
TI  - Size effect on magnetism of Fe thin films in Fe/Ir superlattices.
AB  - In ferromagnetic thin films, the Curie temperature variation with the thickness
      is always considered as continuous when the thickness is varied from n to n+1
      atomic planes. We show that it is not the case for Fe in Fe/Ir superlattices. For
      an integer number of atomic planes, a unique magnetic transition is observed by
      susceptibility measurements, whereas two magnetic transitions are observed for
      fractional numbers of planes. This behavior is attributed to successive
      transitions of areas with n and n+1 atomic planes, for which the T(c)'s are not
      the same. Indeed, the magnetic correlation length is presumably shorter than the
      average size of the terraces. Monte Carlo simulations are performed to support
      this explanation.

PMID- 11329349
TI  - Effects of a bulk perturbation on the ground state of 3D Ising spin glasses.
AB  - We compute and analyze couples of ground states of 3D spin glasses before and
      after applying a volume perturbation which adds to the Hamiltonian a repulsion
      from the true ground state. The physical picture based on replica symmetry
      breaking is in excellent agreement with the observed behavior.

PMID- 11329350
TI  - Polarization rotation via a monoclinic phase in the piezoelectric 92%
      PbZn(1/3)Nb(2/3)O3-8% PbTiO3.
AB  - The origin of ultrahigh piezoelectricity in the relaxor ferroelectric
      PbZn(1/3)Nb(2/3)O3-PbTiO3 was studied with an electric field applied along the
      [001] direction. The zero-field rhombohedral R phase starts to follow the direct
      polarization path to tetragonal symmetry via an intermediate monoclinic M phase,
      but then jumps irreversibly to an alternate path involving a different type of
      monoclinic distortion. Details of the structure and domain configuration of this
      novel phase are described. This result suggests that there is a nearby R-M phase
      boundary as found in the Pb(Ti,Zr)O3 system.

PMID- 11329351
TI  - Effect of van der Waals interactions on the Raman modes in single walled carbon
      nanotubes.
AB  - We have measured the Raman spectrum of individual single walled carbon nanotubes
      in solution and compare it to that obtained from the same starting material where
      the tubes are present in ordered bundles or ropes. Interestingly, the radial mode
      frequencies for the tubes in solution are found to be approximately 10 cm (-1)
      higher than those observed for tubes in a rope, in apparent contradiction to
      lattice dynamics predictions. We suggest that there is no such contradiction, and
      propose that the upshift is due rather to a decreased energy spacing of the Van
      Hove singularities in isolated tubes over the spacings in a rope, thereby
      allowing the same laser excitation to excite different diameter tubes in these
      two samples.

PMID- 11329352
TI  - Two-dimensional time-frequency ultrafast infrared vibrational echo spectroscopy.
AB  - 2D spectrally resolved ultrafast (<200 fs) IR vibrational echo experiments were
      performed on Rh(CO)(2)acac [(acetylacetonato)dicarbonylrhodium (I)]. The 2D
      spectra display features that reflect the 0-1 and 1-2 transitions and the
      combination band transition of the symmetric (S) and antisymmetric (A) CO
      stretching modes. Three oscillations in the data arise from the frequency
      difference between the S and A modes (quantum beats) and the S and A
      anharmonicities. A new explanation is given for these "anharmonic" oscillations.
      Calculations show that spectral resolution enables the 0-1 and 1-2 dephasing to
      be measured independently.

PMID- 11329353
TI  - Single-mode spontaneous emission from a single quantum dot in a three-dimensional
      microcavity.
AB  - The spontaneous emission from an isolated semiconductor quantum dot state has
      been coupled with high efficiency to a single, polarization-degenerate cavity
      mode. The InAs quantum dot is epitaxially formed and embedded in a planar
      epitaxial microcavity, which is processed into a post of submicron diameter. The
      single quantum dot spontaneous emission lifetime is reduced from the noncavity
      value of 1.3 ns to 280 ps, resulting in a single-mode spontaneous emission
      coupling efficiency of 78%.

PMID- 11329354
TI  - Multibit gates for quantum computing.
AB  - We present a general technique to implement products of many qubit operators
      communicating via a joint harmonic oscillator degree of freedom in a quantum
      computer. By conditional displacements and rotations we can implement
      Hamiltonians which are trigonometric functions of qubit operators. With such
      operators we can effectively implement higher order gates such as Toffoli gates
      and C(n)-NOT gates, and we show that the entire Grover search algorithm can be
      implemented in a direct way.

PMID- 11329355
TI  - Budding dynamics of multicomponent membranes.
AB  - The budding of multicomponent membranes is studied by computer simulations and
      scaling arguments. The simulation algorithm combines dynamic triangulation with
      Kawasaki exchange dynamics. The budding process exhibits three distinct time
      regimes: (i) formation and growth of intramembrane domains; (ii) formation of
      many buds; and (iii) coalescence of small buds into larger ones. The coalescence
      regime (iii) is characterized by scaling laws which describe the long-time
      behavior. Thus, the number of buds, N(bud), decays as N(bud) approximately
      1/t(theta) for large time t with theta = 1/2 and theta = 2/3 in the absence and
      the presence of hydrodynamic interactions, respectively.

PMID- 11329356
TI  - Nematic-wetted colloids in the isotropic phase: pairwise interaction, biaxiality,
      and defects.
AB  - We calculate the interaction between two spherical colloidal particles embedded
      in the isotropic phase of a nematogenic liquid. The surface of the particles
      induces wetting nematic coronas that mediate an elastic interaction. In the weak
      wetting regime, we obtain exact results for the interaction energy and the
      texture, showing that defects and biaxiality arise, although they are not
      topologically required. We evidence rich behaviors, including the possibility of
      reversible colloidal aggregation and dispersion. Complex anisotropic self
      assembled phases might be formed in dense suspensions.

PMID- 11329357
TI  - Neural mechanism for a cognitive timer.
AB  - To examine a possible biological mechanism for a cognitive timer, the stochastic
      dynamics of a network of neurons possessing two stable states ("on" and "off"
      states) is studied. The fraction of on neurons existing at t = 0 remains large
      for an extended interval, and then abruptly falls. The distribution of the
      lengths of the interval is scale invariant in the following sense: The ratio (k
      root of (mu(k))/m, with m and mu(k) being the mean and the kth central moment,
      respectively, is invariant under scale transformations of m and mu(k). In the
      special case k = 2, this gives Weber's law, a hallmark of cognitive timing.

PMID- 11329358
TI  - Comment on "revised fine splitting of excitons in diamond".

PMID- 11329361
TI  - Envelope structure of Synechococcus sp. WH8113, a nonflagellated swimming
      cyanobacterium.
AB  - BACKGROUND: Many bacteria swim by rotating helical flagellar filaments. Waterbury
      et al. discovered an exception, strains of the cyanobacterium Synechococcus that
      swim without flagella or visible changes in shape. Other species of cyanobacteria
      glide on surfaces. The hypothesis that Synechococcus might swim using traveling
      surface waves prompted this investigation. RESULTS: Using quick-freeze electron
      microscopy, we have identified a crystalline surface layer that encloses the
      outer membrane of the motile strain Synechococcus sp. WH8113, the components of
      which are arranged in a rhomboid lattice. Spicules emerge in profusion from the
      layer and extend up to 150 nm into the surrounding fluid. These spicules also
      send extensions inwards to the inner cell membrane where motility is powered by
      an ion-motive force. CONCLUSION: The envelope structure of Synechococcus sp.
      WH8113 provides new constraints on its motile mechanism. The spicules are well
      positioned to transduce energy at the cell membrane into mechanical work at the
      cell surface. One model is that an unidentified motor embedded in the cell
      membrane utilizes the spicules as oars to generate a traveling wave external to
      the surface layer in the manner of ciliated eukaryotes.

PMID- 11329360
TI  - Apical accumulation of MARCKS in neural plate cells during neurulation in the
      chick embryo.
AB  - BACKGROUND: The neural tube is formed by morphogenetic movements largely
      dependent on cytoskeletal dynamics. Actin and many of its associated proteins
      have been proposed as important mediators of neurulation. For instance, mice
      deficient in MARCKS, an actin cross-linking membrane-associated protein that is
      regulated by PKC and other kinases, present severe developmental defects,
      including failure of cranial neural tube closure. RESULTS: To determine the
      distribution of MARCKS, and its possible relationships with actin during
      neurulation, chick embryos were transversely sectioned and double labeled with an
      anti-MARCKS polyclonal antibody and phalloidin. In the neural plate, MARCKS was
      found ubiquitously distributed at the periphery of the cells, being conspicuously
      accumulated in the apical cell region, in close proximity to the apical actin
      meshwork. This asymmetric distribution was particularly noticeable during the
      bending process. After the closure of the neural tube, the apically accumulated
      MARCKS disappeared, and this cell region became analogous to the other peripheral
      cell zones in its MARCKS content. Actin did not display analogous variations,
      remaining highly concentrated at the cell subapical territory. The transient
      apical accumulation of MARCKS was found throughout the neural tube axis. The
      analysis of another epithelial bending movement, during the formation of the lens
      vesicle, revealed an identical phenomenon. CONCLUSIONS: MARCKS is transiently
      accumulated at the apical region of neural plate and lens placode cells during
      processes of bending. This asymmetric subcellular distribution of MARCKS starts
      before the onset of neural plate bending. These results suggest possible upstream
      regulatory actions of MARCKS on some functions of the actin subapical meshwork.

PMID- 11329362
TI  - 'I wanna be like Mike (or Gary, or Fiona)!' by Caveman.

PMID- 11329366
TI  - WASP and WAVE family proteins: key molecules for rapid rearrangement of cortical
      actin filaments and cell movement.
AB  - Reorganization of cortical actin filaments plays critical roles in cell movement
      and pattern formation. Recently, the WASP and WAVE family proteins WASP and N
      WASP, and WAVE1, WAVE2 and WAVE3 have been shown to regulate cortical actin
      filament reorganization in response to extracellular stimuli. These proteins each
      have a verprolin-homology (V) domain, cofilin-homology (C) domain and an acidic
      (A) region at the C-terminus, through which they activate the Arp2/3 complex,
      leading to rapid actin polymerization. N-WASP is usually present as an inactive
      form in which the VCA region is masked. Cooperative binding of Cdc42 and
      phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P(2)) exposes the VCA region,
      activating N-WASP. In addition to this activation mechanism, WISH also activates
      N-WASP independently of Cdc42 and PtdIns(4,5)P(2), by binding to the proline-rich
      region of N-WASP. N-WASP activation induces formation of filopodia in vivo. In
      contrast, the ubiquitously expressed form of WAVE2 is activated downstream of
      Rac, leading to formation of lamellipodia. In this case, IRSp53 transmits a
      signal from Rac to WAVE2 through formation of a ternary Rac-IRSp53-WAVE2 complex.
      Thus, N-WASP, which is activated downstream of Cdc42 or independently by WISH,
      induces formation of filopodia and WAVE2, which is activated via IRSp53
      downstream of Rac, induces formation of lamellipodia.

PMID- 11329367
TI  - Cyclin specificity: how many wheels do you need on a unicycle?
AB  - Cyclin-dependent kinase (CDK) activity is essential for eukaryotic cell cycle
      events. Multiple cyclins activate CDKs in all eukaryotes, but it is unclear
      whether multiple cyclins are really required for cell cycle progression. It has
      been argued that cyclins may predominantly act as simple enzymatic activators of
      CDKs; in opposition to this idea, it has been argued that cyclins might target
      the activated CDK to particular substrates or inhibitors. Such targeting might
      occur through a combination of factors, including temporal expression, protein
      associations, and subcellular localization.

PMID- 11329368
TI  - Two kinds of BIR-containing protein - inhibitors of apoptosis, or required for
      mitosis.
AB  - The baculoviral IAP repeat (BIR) is a zinc-binding fold. Some BIR-containing
      proteins (BIRCs), including several from insect viruses, insects and vertebrates,
      are inhibitors of cell death and act by binding to active caspases. Their ability
      to do so can be antagonized by pro-apoptotic insect proteins such as Grim, HID
      and Reaper, or the mammalian protein Diablo/Smac. Members of one structurally
      distinct subgroup of BIR-containing proteins, which are present in yeasts and
      Caenorhabditis elegans as well as insects and vertebrates, do not act as caspase
      inhibitors; instead, they are required for chromosome segregation and
      cytokinesis, and act in concert with inner centromere protein (INCENP) homologues
      and aurora kinase homologues.

PMID- 11329369
TI  - Recruitment and activation of Rac1 by the formation of E-cadherin-mediated cell
      cell adhesion sites.
AB  - Rac1, a member of the Rho family small GTPases, regulates E-cadherin-mediated
      cell-cell adhesion. However, it remains to be clarified how the localization and
      activation of Rac1 are regulated at sites of cell-cell contact. Here, using
      enhanced green fluorescence protein (EGFP)-tagged Rac1, we demonstrate that EGFP
      Rac1 is colocalized with E-cadherin at sites of cell-cell contact and
      translocates to the cytosol during disruption of E-cadherin-mediated cell-cell
      adhesion by Ca(2+) chelation. Re-establishment of cell-cell adhesion by
      restoration of Ca(2)(+) caused EGFP-Rac1 to become relocalized, together with E
      cadherin, at sites of cell-cell contact. Engagement of E-cadherin to the apical
      membrane by anti-E-cadherin antibody (ECCD-2) recruited EGFP-Rac1. We also
      investigated whether E-cadherin-mediated cell-cell adhesion induced Rac1
      activation by measuring the amounts of GTP-bound Rac1 based on its specific
      binding to the Cdc42/Rac1 interactive binding region of p21-activated kinase. The
      formation of E-cadherin-mediated cell-cell adhesion induced Rac1 activation. This
      activation was inhibited by treatment of cells with a neutralizing antibody
      (DECMA-1) against E-cadherin, or with wortmannin, an inhibitor of
      phosphatidylinositol 3-kinase (PI 3-kinase). IQGAP1, an effector of Rac1, and
      EGFP-Rac1 behaved in a similar manner during the formation of E-cadherin-mediated
      cell-cell adhesion. Rac1 activation was also confirmed by measuring the amounts
      of coimmunoprecipitated Rac1 with IQGAP1 during the establishment of cell-cell
      adhesion. Taken together, these results suggest that Rac1 is recruited at sites
      of E-cadherin-mediated cell-cell adhesion and then activated, possibly through PI
      3-kinase.

PMID- 11329370
TI  - Transcriptional activation by the human Hsp70-associating protein Hap50.
AB  - We investigated human Hap50, the large isoform of the previously characterized
      Hsp70/Hsc70-associating protein Hap46, also called BAG-1, for effects on
      transcriptional activities. Overproduction by transient transfection led to
      enhanced expression of reporter gene constructs in various cell types using
      different promoters, suggesting independence of promoter type. Similarly,
      overexpression of Hap50 resulted in increased levels of poly(A)(+ )mRNAs in HeLa,
      COS-7, 3T3 and HTC cells. Concomitantly, the expression of some selected
      endogenous genes, such as those coding for c-Jun and the glucocorticoid receptor,
      was enhanced significantly relative to actin. Nuclear runoff transcription assays
      using HeLa cells showed that the effect is caused by increased transcription
      rates rather than mRNA stabilization. Activation of transcription by Hap50
      occurred at 37 degrees C and did not require prior thermal stress, as is the case
      for Hap46. In accordance with these biological effects, Hap50 is localized
      exclusively in the nuclear compartment of different cell types, whereas Hap46 is
      mostly cytoplasmic in unstressed cells, as revealed by use of fusion constructs
      with green fluorescent protein. High cellular levels of Hap50 were found to make
      cells less susceptible to adverse environmental effects such as heat stress. Our
      data suggest that Hap50 is a nuclear protein that acts in cells to increase the
      transcription of various genes.

PMID- 11329371
TI  - HEMCAM/CD146 downregulates cell surface expression of beta1 integrins.
AB  - HEMCAM/gicerin, an immunoglobulin superfamily protein, is involved in homophilic
      and heterophilic adhesion. It interacts with NOF (neurite outgrowth factor), a
      molecule of the laminin family. Alternative splicing leads to mRNAs coding for
      HEMCAM with a short (HEMCAM-s) or a long cytoplasmic tail (HEMCAM-l). To
      investigate the cellular function of these two variants, we stably transfected
      murine fibroblasts with either form of HEMCAM. Expression of each isoform of this
      protein in L cells delayed proliferation and modified their adhesion properties
      to purified extracellular matrix proteins. Expression of either HEMCAM-s or
      HEMCAM-l inhibited integrin-dependent adhesion and spreading of fibroblasts to
      laminin 1, showing that this phenomenon did not depend on the cytoplasmic region.
      By contrast, L-cell adhesion and spreading to fibronectin depended on the HEMCAM
      isoform expressed. Flow cytometry and immunoprecipitation studies revealed that
      the expression of HEMCAM downregulated expression of the laminin-binding
      integrins alpha3beta1, alpha6beta1 and alpha7beta1, and fibronectin receptor
      alpha5beta1 from the cell surface. Semi-quantitative PCR and northern blot
      experiments showed that the expression of alpha6beta1 integrin modified by HEMCAM
      occurred at a translation or maturation level. Thus, our data demonstrate that
      HEMCAM regulates fibroblast adhesion by controlling beta1 integrin expression.

PMID- 11329372
TI  - Association of the telomere-telomere-binding protein complex of hypotrichous
      ciliates with the nuclear matrix and dissociation during replication.
AB  - Telomeric interactions with the nuclear matrix have been described in a variety
      of eukaryotic cells and seem to be essential for specific nuclear localization.
      Macronuclear DNA of hypotrichous ciliates occurs in small gene-sized DNA
      molecules, each being terminated by telomeres. Each macronucleus contains over
      10(8 )individual DNA molecules. Owing to the high number of telomeres present in
      this nucleus it provides an excellent model to study telomere behaviour
      throughout the cell cycle. In this study we provide experimental evidence that
      the telomere-telomere-binding protein (TEBP) complex specifically interacts with
      components of the nuclear matrix in vivo. In the course of replication the
      specific interaction of the TEBP with components of the nuclear matrix is
      resolved and an attachment of the telomeres to the matrix no longer occurs.

PMID- 11329373
TI  - Accumulation of soluble and nucleolar-associated p53 proteins following cellular
      stress.
AB  - The tumor suppressor p53 is a nucleocytoplasmic shuttling protein that
      accumulates in the nucleus of cells exposed to various cellular stresses. One
      important role of nuclear p53 is to mobilize a stress response by transactivating
      target genes such as the p21(Waf1) gene. In this study, we investigated more
      closely the localization of p53 in cells following various stresses.
      Immunocytochemistry of fixed human fibroblasts treated with either UV light, the
      kinase and transcription inhibitor DRB or the proteasome inhibitor MG132 revealed
      abundant p53 localized to the nucleus. When cells treated with UV or DRB were
      permeabilized prior to fixation to allow soluble proteins to diffuse, the nuclear
      p53 signal was abolished. However, in cells treated with MG132, residual p53
      localized to distinct large foci. Furthermore, nucleolin co-localized with p53 to
      these foci, suggesting that these foci were nucleolar structures. Interestingly,
      the MDM2 protein was found to co-localize with p53 to nucleolar structures
      following proteasome inhibition. Our results suggest that the p53 proteins
      accumulating in the nucleus following UV-irradiation or blockage of transcription
      are freely soluble and, thus, should be able to roam the nucleus to ensure high
      occupancy of p53 binding sites. However, inhibition of proteasome activity may be
      a unique stress in that it leads to the sequestering of p53 proteins to the
      nucleolus, thereby blunting the p53-mediated transactivation of target genes.

PMID- 11329374
TI  - Nuclear dispositions of subtelomeric and pericentromeric chromosomal domains
      during meiosis in asynaptic mutants of rye (Secale cereale L.).
AB  - The nuclear dispositions of subtelomeric and pericentromeric domains in pollen
      mother cells (PMCs) were tracked during meiosis in wildtype and two asynaptic
      mutants of rye (Secale cereale L.) by means of fluorescence in situ hybridization
      (FISH). Homozygotes for sy1 and sy9 non-allelic mutations form axial elements
      during leptotene of male meiosis, but fail to form synaptonemal complexes.
      Consequently, recombination is severely impaired, and high univalency is observed
      at metaphase I. Simultaneous FISH with pSc200 subtelomeric tandem repeat and CCS1
      centromeric sequence revealed that at pre-meiotic interphase the two domains are
      in a bipolar Rabl orientation in both the PMCs and tapetal cells. At the onset of
      meiotic prophase, the subtelomeric regions in PMCs of wildtype and sy9 cluster
      into a typical bouquet conformation. The timing of this event in rye is
      comparable with that in wheat, and is earlier than that observed in other
      organisms, such as maize, yeast and mammals. This arrangement is retained until
      later in leptotene and zygotene when the pericentromeric domains disperse and the
      subtelomeric clusters fragment. The mutant phenotype of sy9 manifests itself
      during leptotene to zygotene, when the pericentromeric regions become distinctly
      more distended than in wildtype, and largely fail to pair during zygotene. This
      indicates that difference in the nature or timing of chromosome condensation in
      this region is the cause or consequence of asynapsis. By contrast, sy1 fails to
      form comparable aggregates of subtelomeric regions at leptotene in only half of
      the nuclei studied. Instead, two to five aggregates are formed that fail to
      disperse at later stages of meiotic prophase. In addition, the pericentromeric
      regions disperse prematurely at leptotene and do not associate in pairs at any
      subsequent stage. It is supposed that the sy1 mutation could disrupt the nuclear
      disposition of centromeres and telomeres at the end of pre-meiotic interphase,
      which could cause, or contribute to, its asynaptic phenotype.

PMID- 11329375
TI  - Prolactin signalling to milk protein secretion but not to gene expression depends
      on the integrity of the Golgi region.
AB  - Prolactin added to the incubation medium of lactating mammary epithelial cells is
      transported from the basal to the apical region of cells through the Golgi region
      and concomitantly stimulates arachidonic acid release and protein milk secretion.
      We report that when PRL is added after disorganisation of the Golgi apparatus by
      brefeldin A treatment, prolactin signalling to expression of genes for milk
      proteins and prolactin endocytosis are not affected. However, prolactin transport
      to the apical region of cells (transcytosis), as well as prolactin-induced
      arachidonic acid release and subsequent stimulation of the secretion of caseins,
      which are located in a post-Golgi compartment, are inhibited. This inhibition was
      not a consequence of damage to the secretory machinery, as under the same
      conditions, protein secretion could be stimulated by the addition of arachidonic
      acid to the incubation medium. Thus, it is possible to discriminate between
      prolactin-induced actions that are dependent (signalling to milk protein
      secretion) or independent (signalling to milk gene expression) on the integrity
      of the Golgi apparatus. These results suggest that these two biological actions
      may be transduced via distinct intracellular pathways, and support the hypothesis
      that prolactin signals may be emitted at various cellular sites.

PMID- 11329376
TI  - Depletion of rafts in late endocytic membranes is controlled by NPC1-dependent
      recycling of cholesterol to the plasma membrane.
AB  - In mammalian cells, cholesterol is thought to associate with sphingolipids to
      form lateral membrane domains termed rafts. Increasing evidence suggests that
      rafts regulate protein interactions, for example, during signalling,
      intracellular transport and host-pathogen interactions. Rafts are present in
      cholesterol-sphingolipid-enriched membranes, including early and recycling
      endosomes, but whether rafts are found in late endocytic organelles has not been
      analyzed. In this study, we analyzed the association of cholesterol and late
      endosomal proteins with low-density detergent-resistant membranes (DRMs) in
      normal cells and in cells with lysosomal cholesterol-sphingolipid accumulation.
      In normal cells, the majority of [(3)H]cholesterol released from
      [(3)H]cholesterol ester-LDL associated with detergent-soluble membranes, was
      rapidly transported to the plasma membrane and became increasingly insoluble with
      time. In Niemann-Pick C1 (NPC1) protein-deficient lipidosis cells, the
      association of LDL-cholesterol with DRMs was enhanced and its transport to the
      plasma membrane was inhibited. In addition, the NPC1 protein was normally
      recovered in detergent-soluble membranes and its association with DRMs was
      enhanced by lysosomal cholesterol loading. Moreover, lysosomal cholesterol
      deposition was kinetically paralleled by the sequestration of sphingolipids and
      formation of multilamellar bodies in late endocytic organelles. These results
      suggest that late endocytic organelles are normally raft-poor and that
      endocytosed LDL-cholesterol is efficiently recycled to the plasma membrane in an
      NPC1-dependent process. The cholesterol-sphingolipid accumulation characteristic
      to NPC disease, and potentially to other sphingolipidoses, causes an overcrowding
      of rafts forming lamellar bodies in the degradative compartments.

PMID- 11329377
TI  - Normal membrane localization and actin association of the NF2 tumor suppressor
      protein are dependent on folding of its N-terminal domain.
AB  - The neurofibromatosis type 2 (NF2) tumor suppressor protein, known as schwannomin
      or merlin, is involved in linking membrane proteins to the cytoskeleton. Like the
      related ERM proteins, schwannomin has long been suspected of exhibiting a complex
      3D organization caused by the association of different regions within the
      protein. Intramolecular interactions characterized to date are linking N-terminal
      sequences of the protein to C-terminal sequences. Here, we demonstrate, by a
      biochemical approach, the existence of a structured domain entirely contained
      within the N-terminal half of schwannomin. This structure, which is resistant to
      chymotryptic digestion, encompasses the FERM domain (residues 19-314), but
      excludes the 18 extreme N-terminal residues specific to schwannomin. The
      structure is disrupted by some, but not all, naturally occurring NF2 mutations.
      We investigated the significance of this structured domain in schwannomin
      cellular functions and found that normal schwannomin localization beneath the
      plasma membrane is directly dependent on proper folding of the N-terminal domain.
      In addition, folding of the N-terminal domain influences schwannomin interaction
      with actin through two novel actin-binding sites located in this region. These
      results suggest that loss of activity of several naturally occurring schwannomin
      mutants is due to disruption of the fold of the N-terminal domain, leading to
      loss of both membrane localization and actin association.

PMID- 11329378
TI  - The hSkn-1a POU transcription factor enhances epidermal stratification by
      promoting keratinocyte proliferation.
AB  - Skn-1a is a POU transcription factor that is primarily expressed in the epidermis
      and is known to modulate the expression of several genes associated with
      keratinocyte differentiation. However, the formation of a stratified epidermis
      requires a carefully controlled balance between keratinocyte proliferation and
      differentiation, and a role for Skn-1a in this process has not been previously
      demonstrated. Here, our results show, surprisingly, that human Skn-1a contributes
      to epidermal stratification by primarily promoting keratinocyte proliferation and
      secondarily by enhancing the subsequent keratinocyte differentiation. In
      organotypic raft cultures of both primary human keratinocytes and immortalized
      HaCaT keratinocytes, human Skn-1a expression is associated with increased
      keratinocyte proliferation and re-epithelialization of the dermal substrates,
      resulting in increased numbers of keratinocytes available for the differentiation
      process. In these same raft cultures, human Skn-1a expression enhances the
      phenotypic changes of keratinocyte differentiation and the upregulated expression
      of keratinocyte differentiation genes. Conversely, expression of a dominant
      negative human Skn-1a transcription factor lacking the C-terminal transactivation
      domain blocks keratinocytes from proliferating and stratifying. Keratinocyte
      stratification is dependent on a precise balance between keratinocyte
      proliferation and differentiation, and our results suggest that human Skn-1a has
      an important role in maintaining epidermal homeostasis by promoting keratinocyte
      proliferation.

PMID- 11329379
TI  - Leukotriene D(4) affects localisation of vinculin in intestinal epithelial cells
      via distinct tyrosine kinase and protein kinase C controlled events.
AB  - Local inflammatory reactions affect the integrity of intestinal epithelial cells,
      such as E-cadherin-mediated cell-cell interactions. To elucidate this event, we
      investigated the effects of an inflammatory mediator, leukotriene D(4 )(LTD(4)),
      on the phosphorylation status and properties of vinculin, a multi-binding protein
      known to interact with both the E-cadherin-catenin complex and the cytoskeleton.
      Treatment of an intestinal epithelial cell line with LTD(4 )induced rapid
      tyrosine phosphorylation of vinculin, which was blocked by the Src family
      tyrosine kinase inhibitor PP1. Simultaneously, LTD(4) caused an increased
      association between vinculin and actin, and that association was decreased by
      PP1. LTD(4) also induced dissociation of vinculin from alpha-catenin without
      affecting the catenin complex itself. This dissociation was not blocked by PP1
      but was mimicked by the protein kinase C (PKC) activator 12-O
      tetradecanoylphorbol 13-acetate (TPA). Also, the PKC inhibitor GF109203X
      abolished both the LTD(4)- and the TPA-induced dissociation of vinculin from
      alpha-catenin. Furthermore, LTD(4) caused a colocalisation of vinculin with PKC
      alpha in focal adhesions. This accumulation of vinculin was blocked by
      transfection with a dominant negative inhibitor of PKC (PKC regulatory domain)
      and also by preincubation with either GF109203X or PP1. Thus, various LTD(4)
      induced phosphorylations of vinculin affect the release of this protein from
      catenin complexes and its association with actin, two events that are necessary
      for accumulation of vinculin in focal adhesions. Functionally this LTD(4)-induced
      redistribution of vinculin was accompanied by a PKC-dependent upregulation of
      active beta1 integrins on the cell surface and an enhanced beta1 integrin
      dependent adhesion of the cells to collagen IV.

PMID- 11329380
TI  - End13p/Vps4p is required for efficient transport from early to late endosomes in
      Saccharomyces cerevisiae.
AB  - end13-1 was isolated in a screen for endocytosis mutants and has been shown to
      have a post-internalisation defect in endocytic transport as well as a defect in
      vacuolar protein sorting (Vps(-) phenotype), leading to secretion of newly
      synthesised vacuolar proteins. Here we demonstrate that END13 is identical to
      VPS4, encoding an AAA (ATPase associated with a variety of cellular activities)
      family ATPase. We also report that the end13-1 mutation is a serine 335 to
      phenylalanine substitution in the AAA-ATPase domain of End13p/Vps4p. It has been
      reported that mutant cells lacking End13p/Vps4p (end13(vps4)Delta) accumulate
      endocytosed marker dyes, plasma membrane receptors and newly synthesised vacuolar
      hydrolase precursors in an endosomal compartment adjacent to the vacuole
      (prevacuolar compartment, or PVC). We find, however, that the end13 mutants have
      defects in transport of endocytosed fluorescent dyes, plasma membrane receptors
      and ligands from small peripherally located early endosomes to larger late
      endosomes, which are often located adjacent to the vacuole. Our results indicate
      that End13p/Vps4p may play an important role in multiple steps of membrane
      traffic through the endocytic pathway.

PMID- 11329381
TI  - Rma1, a novel type of RING finger protein conserved from Arabidopsis to human, is
      a membrane-bound ubiquitin ligase.
AB  - Rma1 is a protein with a RING finger motif and a C-terminal membrane-anchoring
      domain and is well conserved among higher eukaryotes. We show that fusion
      proteins between maltose binding protein (MBP) and human or Arabidopsis Rma1 are
      polyubiquitinated, when incubated with the rabbit reticulocyte or the wheat germ
      lysate, respectively. The polyubiquitination of MBP-Rma1 has been reconstituted
      by incubation with purified ubiquitin, the ubiquitin-activating enzyme E1, and
      one of the two ubiquitin-conjugating E2 enzymes (Ubc4 or UbcH5a). Other E2
      enzymes tested, E2-20k, E2-25k, Ubc3 and Ubc8, are not able to confer this
      modification. Mutational analysis shows that the RING finger motif of Rma1 is
      necessary for the auto-ubiquitination of MBP-Rma1. Thus, Rma1 represents a novel,
      membrane-bound type of ubiquitin ligase E3, which probably functions with the
      Ubc4/5 subfamily of E2. The MBP moiety but not Rma1 itself is ubiquitinated in
      the auto-ubiquitination reaction of MBP-Rma1. Free MBP in solution is not a
      substrate of Rma1. These observations indicate that bringing the substrate into
      its physical vicinity is very important for the action of ubiquitin ligase.

PMID- 11329382
TI  - Relationships between EEA1 binding partners and their role in endosome fusion.
AB  - Homotypic fusion between early endosomes requires the phosphatidylinositol 3
      phosphate (PI3P)-binding protein, Early Endosomal Autoantigen 1 (EEA1). We have
      investigated the role of other proteins that interact with EEA1 in the fusion of
      early endosomes derived from Baby Hamster Kidney (BHK) cells. We confirm a
      requirement for syntaxin 13, but additionally show that the assay is equally
      sensitive to reagents specifically targeted against syntaxin 6. Binding of EEA1
      to immobilised GST-syntaxin 6 and 13 was directly compared; only syntaxin 6
      formed a stable complex with EEA1. Early endosome fusion requires the release of
      intravesicular calcium, and calmodulin plays a vital role in the fusion pathway,
      as judged by sensitivity to antagonists. We demonstrate that both EEA1 and
      syntaxin 13 interact with calmodulin. In the case of EEA1, binding to calmodulin
      requires an IQ domain, which is adjacent to a C-terminal FYVE domain that
      specifically binds to PI3P. We have assessed the influence of protein binding
      partners on EEA1 interaction with PI3P and find that both calmodulin and rab5-GTP
      are antagonistic to PI3P binding, whilst syntaxins 6 and 13 have no effect. These
      studies reveal a complex network of interactions between the proteins required
      for endosome fusion.

PMID- 11329383
TI  - Diversity in psychiatry: or, why did we become psychiatrists?

PMID- 11329384
TI  - Partial versus full hospitalization for adults in psychiatric distress: a
      systematic review of the published literature (1957-1997).
AB  - OBJECTIVE: The authors reviewed published research that compared partial and full
      hospitalization as alternative programs for the care of mentally ill adults, with
      the goal of both systematizing the knowledge base and providing directions for
      future research. METHOD: Studies published since 1950 were obtained through
      manual and electronic searches. Results were stratified by outcome domain, type
      of measure used to report between-group differences (global, partial, or rate
      based), and time of assessment. Effect sizes were computed and combined within a
      random-effects framework. RESULTS: Eighteen investigations published between 1957
      and 1997 were systematically reviewed. Over half of eligible patients were
      excluded a priori; diagnostic severity of enrollees varied widely. On measures of
      psychopathology, social functioning, family burden, and service utilization, the
      authors found no evidence of differential outcome in the selected patient
      population admitted to the studies reviewed. Rates of satisfaction with services
      suggested an advantage for partial hospitalization within 1 year of discharge,
      with the gap being largest at 7-12 months. CONCLUSIONS: Although partial
      hospitalization is not an option for all patients requiring intensive services,
      outcomes of partial hospitalization patients in these studies were no different
      from those of inpatients. Further, patients and families were more satisfied with
      partial hospitalization in the short term. Weaknesses of the studies limited the
      scope of our inquiry and the generalizability of findings. Positive findings
      require replication under the present circumstances of mental health care, and
      more research is needed to identify predictors of differential outcome and
      successful partial hospitalization. A clearer definition of partial
      hospitalization will help consolidate its role in the continuum of mental health
      services.

PMID- 11329385
TI  - Emily Dickinson revisited: a study of periodicity in her work.
AB  - OBJECTIVE: Emily Dickinson, arguably one of America's foremost poets, is
      characterized by critics as able to capture extreme emotional states in her
      greatest work. Recent dating of her poems offers the periodicity of her writing
      as a behavior that can be examined for patterns of affective illness that may
      relate to these states. METHOD: The bulk of Dickinson's work was written during a
      clearly defined 8-year period when she was age 28-35. Poems written during that
      period, 1858-1865, were grouped by year and examined for annual and seasonal
      distribution. RESULTS: Her 8-year period of productivity was marked by two 4-year
      phases. The first shows a seasonal pattern characterized by greater creative
      output in spring and summer and a lesser output during the fall and winter. This
      pattern was interrupted by an emotional crisis that marked the beginning of the
      second phase, a 4-year sustained period of greatly heightened productivity and
      the emergence of a revolutionary poetic style. CONCLUSIONS: These data, supported
      by excerpts from letters to friends during this period of Dickinson's life,
      demonstrate seasonal changes in mood during the first four years of major
      productivity, followed by a sustained elevation of creative energy, mood, and
      cognition during the second. They suggest, as supported by family history, a
      bipolar pattern previously described in creative artists.

PMID- 11329386
TI  - The human genome sequence: the human genome ii: sources of genetic variation.

PMID- 11329388
TI  - Contingency management interventions: from research to practice.

PMID- 11329389
TI  - Images in psychiatry. Maurice Dide, 1873-1944.

PMID- 11329390
TI  - Sundowning and circadian rhythms in Alzheimer's disease.
AB  - OBJECTIVE: The goal of this study was to determine changes of circadian rhythms
      induced by Alzheimer's disease and to explore relationships among rhythm
      disturbances, sundowning, and sleep disturbances in patients with Alzheimer's
      disease. "Sundowning" is the occurrence or exacerbation of behavioral symptoms of
      Alzheimer's disease in the afternoon and evening. METHOD: Circadian rhythms of
      core body temperature and motor activity were measured in 25 patients with
      diagnoses of probable Alzheimer's disease and in nine healthy individuals. The
      subjects with Alzheimer's disease were divided according to the occurrence of
      sundowning as determined by staff reports. RESULTS: The subjects with Alzheimer's
      disease had less diurnal motor activity, a higher percentage of nocturnal
      activity, lower interdaily stability of motor activity, and a later activity
      acrophase (time of peak) than did the healthy individuals. They also had a higher
      mesor (fitted mean) temperature, higher amplitude of the fitted cosine
      temperature curve, and later temperature acrophase than did the healthy subjects.
      The severity of sundowning was associated with later acrophase of temperature,
      less correlation of circadian temperature rhythm with a 24-hour cycle, and lower
      amplitude of temperature curve. CONCLUSIONS: These data indicate that Alzheimer's
      disease causes disturbances of circadian rhythms and that sundowning is related
      to a phase delay of body temperature caused by Alzheimer's disease.

PMID- 11329391
TI  - Assessing the competence of persons with Alzheimer's disease in providing
      informed consent for participation in research.
AB  - OBJECTIVE: The capacity of persons with Alzheimer's disease or other
      neuropsychiatric disorders for giving consent to participate in research has come
      under increasing scrutiny. While instruments for measuring abilities related to
      capacity have been developed, how they should be used to categorize subjects as
      capable or incapable is not clear. A criterion validation study was carried out
      to help address this question. METHOD: The authors measured the ability of 37
      subjects with mild-to-moderate Alzheimer's disease and 15 elderly comparison
      subjects to provide consent for participation in a hypothetical clinical trial.
      Using the judgment of three experts as the criterion standard, the authors
      performed a receiver operator characteristic analysis for the capacity ability
      measures from the MacArthur Competence Assessment Tool-Clinical Research VERSION:
      The results were compared with categorizations of capacity status that were based
      on normative values. RESULTS: While most comparison subjects scored perfectly on
      all measures of the competence assessment tool, the majority of the group with
      Alzheimer's disease showed significant decision-making impairment. Thresholds
      based on normative values resulted in 84% (N=31) of the Alzheimer's disease
      subjects being rated as incapable on at least one ability; thresholds based on
      expert judgment resulted in 62% (N=23) failing to meet cutoff scores on at least
      one ability. CONCLUSIONS: Even relatively mild Alzheimer's disease significantly
      impairs consent-giving capacity. But differentiating capable from incapable
      subjects remains an issue despite the aid of standardized tools. More research is
      needed to understand the relationship between subject factors (performance on
      ability measures) and categorical judgments about their capacity.

PMID- 11329392
TI  - Evidence for a locus on chromosome 1 that influences vulnerability to alcoholism
      and affective disorder.
AB  - OBJECTIVE: Depression (major depression or depressive syndrome) is more prevalent
      in alcoholic than in nonalcoholic subjects in families with multiple members with
      alcoholism studied as part of the Collaborative Study on the Genetics of
      Alcoholism (National Institute on Alcohol Abuse and Alcoholism). First-degree
      relatives of probands with comorbid alcoholism and depression have a higher
      prevalence of both disorders than relatives of probands with alcoholism alone,
      and both groups have a higher prevalence than the relatives of comparison
      subjects selected without regard to psychopathology. Data from the collaborative
      study were used to test three phenotypes (comorbid alcoholism and depression,
      alcoholism or depression, and depression) for genetic linkage. METHOD: Genome
      wide sibling-pair linkage analyses were performed with the phenotypes comorbid
      alcoholism and depression, alcoholism or depression, and depression (major
      depression or depressive syndrome). Analyses were performed in two data sets
      (initial and replication data sets) from subject groups ascertained with
      identical criteria, as well as in the combined data set. RESULTS: Peak lod scores
      on chromosome 1 (near 120 centimorgan) for the alcoholism or depression phenotype
      were 5.12, 1.52, and 4.66 in the initial, replication, and combined data sets,
      respectively. The corresponding lod scores on chromosome 2 were 2.79, 0.20, and
      3.26; on chromosome 6, they were 3.39, 0.00, and 0.92; and on chromosome 16, they
      were 3.13, 0.00, and 2.06. Lod scores on chromosome 2 for the comorbid alcoholism
      and depression phenotype in the three data sets were 0.00, 4.12, and 2.16,
      respectively. CONCLUSIONS: The results suggest that a gene or genes on chromosome
      1 may predispose some individuals to alcoholism and others to depression (which
      may be alcohol induced). Loci on other chromosomes may also be of interest.

PMID- 11329393
TI  - Meta-analysis of the relationship between HIV infection and risk for depressive
      disorders.
AB  - OBJECTIVE: Each of 10 published studies investigating the relationship between
      HIV infection and risk for depressive disorders concluded that HIV-positive
      individuals are at no greater risk for depression than comparable HIV-negative
      individuals. This study used meta-analytic techniques to further examine the
      relationship between depressive disorders and HIV infection. METHOD: Meta
      analytic techniques were used to aggregate and reanalyze the data from 10 studies
      that compared HIV-positive and HIV-negative individuals for rates of major
      depressive disorder (N=2,596) or dysthymic disorder (N=1,822). RESULTS: The
      frequency of major depressive disorder was nearly two times higher in HIV
      positive subjects than in HIV-negative comparison subjects. On the other hand,
      findings were inconclusive with regard to dysthymic disorder. Rates of depression
      do not appear to be related to the sexual orientation or disease stage of
      infected individuals. CONCLUSIONS: Although the majority of HIV-positive
      individuals appear to be psychologically resilient, this meta-analysis provides
      strong evidence that HIV infection is associated with a greater risk for major
      depressive disorder. Future research should focus on identifying pathways of risk
      and resilience for depression within this population.

PMID- 11329394
TI  - Depressive symptoms, satisfaction with health care, and 2-year work outcomes in
      an employed population.
AB  - OBJECTIVE: The relationship of depressive symptoms, satisfaction with health
      care, and 2-year work outcomes was examined in a national cohort of employees.
      METHOD: A total of 6,239 employees of three corporations completed surveys on
      health and satisfaction with health care in 1993 and 1995. This study used
      bivariate and multivariate analyses to examine the relationships of depressive
      symptoms (a score below 43 on the Medical Outcomes Study Short-Form Health Survey
      mental component summary), satisfaction with a variety of dimensions of health
      care in 1993, and work outcomes (sick days and decreased effectiveness in the
      workplace) in 1995. RESULTS: The odds of missed work due to health problems in
      1995 were twice as high for employees with depressive symptoms in both 1993 and
      1995 as for those without depressive symptoms in either year. The odds of
      decreased effectiveness at work in 1995 was seven times as high. Among
      individuals with depressive symptoms in 1993, a report of one or more problems
      with clinical care in 1993 predicted a 34% increase in the odds of persistent
      depressive symptoms and a 66% increased odds of decreased effectiveness at work
      in 1995. There was a weaker association between problems with plan administration
      and outcomes. CONCLUSIONS: Depressive disorders in the workplace persist over
      time and have a major effect on work performance, most notably on "presenteeism,"
      or reduced effectiveness in the workplace. The study's findings suggest a
      potentially important link between consumers' perceptions of clinical care and
      work outcomes in this population.

PMID- 11329395
TI  - Neuropsychological dysfunction in depressed suicide attempters.
AB  - OBJECTIVE: Neuropsychological deficits in the context of psychiatric disease may
      be associated with suicide risk. In this study, neuropsychological performance
      was compared among depressed patients with at least one prior suicide attempt of
      high lethality, depressed patients with low-lethality prior attempts, depressed
      patients with no prior suicide attempts, and nonpatients. METHOD: Fifty
      unmedicated patients in a major depressive episode (21 with no history of suicide
      attempts and 14 and 15 patients with previous attempts of low and high lethality,
      respectively) and 22 nonpatients were assessed. Groups were comparable in age,
      education, occupational level, and estimated premorbid intelligence. The
      neuropsychological battery produced scores within five composite domains: general
      intellectual functioning (current), motor functioning, attention, memory, and
      executive functioning. RESULTS: Patients whose prior suicide attempts were of
      high lethality performed significantly worse than all groups on tests of
      executive functioning and were the only group to perform significantly worse than
      nonpatients on tests of general intellectual functioning, attention, and memory.
      A discriminant function analysis revealed two prominent dimensions in the data:
      one that discriminated high-lethality suicide attempters from all other groups
      (primarily associated with performance on tests of executive functioning) and
      another that discriminated all depressed patient groups from nonpatients
      (associated with performance on measures of attention and memory). For the
      patients with high-lethality prior suicide attempts, deficits did not appear to
      reflect diffuse brain damage from past attempts, since the results of tests
      commonly affected by diffuse injury were not selectively impaired. CONCLUSIONS:
      Neuropsychological deficits in depressed patients with high-lethality prior
      suicide attempts suggest impairment of executive functioning beyond that
      typically found in major depression. This more extensive neuropsychological
      impairment in the context of depression may be a risk factor for severe suicide
      attempts.

PMID- 11329396
TI  - Delusions and suicidality.
AB  - OBJECTIVE: Delusions have been considered a risk factor for suicidal behavior. To
      determine whether specific delusion types are related to suicidal behaviors, the
      authors compared the clinical characteristics of patients with mood disorders and
      schizophrenia who did and did not have a history of suicide attempts. METHOD:
      After admission for inpatient or outpatient psychiatric treatment, 429 patients
      (ages 14-72 years; 47.1% male; and 73.0% Caucasian) were assessed with a
      structured clinical interview that generated axis I and II diagnoses. In
      addition, their psychiatric symptoms, history of suicide attempts, and overall
      functioning were rated. RESULTS: Data for three diagnostic subgroups (223
      patients with major depression, 150 with schizophrenia, and 56 with bipolar
      disorder) were analyzed separately. Multivariate analyses did not find evidence
      of a relationship between delusions and history of suicidal ideation or suicide
      attempts in any of the diagnostic groups. CONCLUSIONS: This study did not find
      evidence that the presence of delusions distinguished persons with or without a
      history of suicide attempt.

PMID- 11329398
TI  - Season of birth among patients with schizophrenia and their siblings: evidence
      for the procreational habits hypothesis.
AB  - OBJECTIVE: The birth rate of patients with schizophrenia during the winter and
      spring months is 5%-8% higher worldwide than the birth rate of the general
      population in the winter and spring months. Seasonal variation of births among
      the unaffected siblings of patients with schizophrenia has not been studied with
      adequate sample sizes. The authors investigated the seasonal variation of births
      among siblings of patients with schizophrenia in a large, nationwide,
      representative patient and sibling population. METHOD: Finnish patients with
      schizophrenia born from 1950 to 1969 (N=15,389) were identified from three
      nationwide health care registers. Unaffected siblings of these patients born in
      the same time period (N=37,819) were identified from the Finnish National
      Population REGISTER: The seasonal variation of births among patients and siblings
      were examined by using a log-linear model. Explanatory variables were sex, year
      of birth categorized into four 5-year groups, and seasonal variation, which was
      analyzed by fitting a short Fourier series to the monthly birth data. RESULTS:
      The odds for having been born during the winter-spring months were slightly
      higher among both siblings and patients in all birth-year groups. However,
      patients born from 1955 to 1959 showed prominent seasonal variation of births,
      but the magnitude of this variation remained unchanged among siblings.
      CONCLUSIONS: Seasonal variation of births among patients with schizophrenia may
      consist of two factors: 1) parental procreational habits causing a slight excess
      of births of both patients and unaffected siblings during the winter-spring
      months and 2) irregular environmental factors that considerably increase the
      magnitude of the seasonal variation of births among patients but not their
      siblings.

PMID- 11329397
TI  - The dexamethasone suppression test and suicide prediction.
AB  - OBJECTIVE: Despite the substantial risks of eventual suicide associated with
      major depressive disorder, clinicians lack robust predictors with which to
      quantify these risks. This study compared the validity of demographic and
      historical risk factors with that of the dexamethasone suppression test (DST), a
      clinically practical measure of hyperactivity of the hypothalamic-pituitary
      adrenal (HPA) axis. METHOD: Seventy-eight inpatients with Research Diagnostic
      Criteria major depressive disorder or schizoaffective disorder, depressed type,
      entered a long-term follow-up study between 1978 and 1981, and, in addition,
      underwent a 1-mg DST. The number of suicides in this group during a 15-year
      follow-up period was determined, and the predictive validity of four demographic
      and historical risk factors reported in the literature to be consistently
      predictive of suicide in depressed patients was compared to the predictive
      validity of the DST results. RESULTS: Thirty-two of the 78 patients had abnormal
      DST results. Survival analyses showed that the estimated risk for eventual
      suicide in this group was 26.8%, compared to only 2.9% among patients who had
      normal DST results. None of the demographic and historical risk factors examined
      in the study significantly distinguished those who later committed suicide from
      those who did not. CONCLUSIONS: In efforts to predict and prevent suicidal
      behavior in patients with major depressive disorder, HPA-axis hyperactivity, as
      reflected in DST results, may provide a tool that is considerably more powerful
      than the clinical predictors currently in use. Research on the pathophysiology of
      suicidal behavior in major depressive disorder should emphasize the HPA axis and
      its interplay with the serotonin system.

PMID- 11329399
TI  - Clinical and cognitive factors associated with verbal memory task performance in
      patients with schizophrenia.
AB  - OBJECTIVE: The authors have previously shown the role of depression, slowing of
      processing speed, and selective attention deficit in verbal memory task
      performance in schizophrenia. They wished to determine the specific contribution
      of each of these factors to various types of memory impairment. METHOD: The
      negative symptom score from the Positive and Negative Syndrome Scale, the
      Hamilton Depression Rating Scale score, a measure of processing speed, and a
      measure of selective attention were entered as predictors in regression analyses.
      Furthermore, analyses of covariance were conducted on the memory measures to test
      the significance of the differences between schizophrenic patients and healthy
      comparison subjects after control for processing speed and selective attention.
      RESULTS: Depression was associated only with deep encoding reflected by semantic
      clustering. Selective attention was associated only with superficial encoding
      reflected by serial recall. Slowing of processing speed was associated with both
      deep and superficial encoding. Negative symptoms were not associated with memory
      impairment except for the avolition item from the Scale for the Assessment of
      Negative Symptoms. Processing speed accounted for all the group differences on
      the memory measures that reflected superficial encoding. In addition, a subgroup
      of patients with no or minor depression was not significantly impaired on deep
      encoding relative to the healthy comparison group. CONCLUSIONS: The authors
      suggest that verbal memory impairment in schizophrenia is a consequence of
      depression and slowness, rather than a primary feature of the disease.

PMID- 11329400
TI  - A randomized double-blind study of risperidone and olanzapine in the treatment of
      schizophrenia or schizoaffective disorder.
AB  - OBJECTIVE: The safety and efficacy of risperidone and olanzapine were compared in
      a double-blind trial that used doses widely accepted in clinical practice.
      METHOD: Subjects (N=377) who met DSM-IV criteria for schizophrenia or
      schizoaffective disorder were randomly assigned to receive 2-6 mg/day of
      risperidone (mean modal dose=4.8 mg/day) or 5-20 mg/day of olanzapine (mean modal
      dose=12.4 mg/day) for 8 weeks. RESULTS: The two study groups were similar at
      baseline except that the olanzapine group was slightly younger than the
      risperidone group. Seventy-five percent of the participants completed the trial,
      with no between-treatment differences in the proportion of dropouts. Similar
      proportions of the risperidone and olanzapine groups reported extrapyramidal
      symptoms (24% and 20%, respectively). Severity of extrapyramidal symptoms was low
      in both groups, with no between-group differences. Total Positive and Negative
      Syndrome Scale scores and scores on the five Positive and Negative Syndrome Scale
      factors were improved in both groups at week 8 (subjects who completed the study)
      and endpoint (all subjects, including dropouts). There were overall between
      treatment differences in efficacy. Comparison of individual factors found no
      significant differences at endpoint; at week 8, however, improvements on Positive
      and Negative Syndrome Scale factors for positive symptoms and anxiety/depression
      were greater with risperidone than olanzapine. An increase in body weight of > or
      =7% was seen in 27% of olanzapine participants and 12% of risperidone
      participants. CONCLUSIONS: Both treatments were well tolerated and efficacious.
      The frequency and severity of extrapyramidal symptoms were similar in the two
      treatment groups. Greater reductions in severity of positive and affective
      symptoms were seen with risperidone than with olanzapine treatment among study
      completers. There was no measure on which olanzapine was superior. Greater weight
      gain was associated with olanzapine than with risperidone treatment.

PMID- 11329401
TI  - Brain Regional alpha-[11C]methyl-L-tryptophan trapping in impulsive subjects with
      borderline personality disorder.
AB  - OBJECTIVE: Neurotransmission of serotonin (or 5-hydroxytryptamine [5-HT]) is
      thought to be disturbed in patients exhibiting impulsive behaviors. However,
      until recently it has not been possible to test this hypothesis in the brains of
      living humans. METHOD: Unidirectional trapping of the 5-HT precursor analog alpha
      [(11)C]methyl-L-tryptophan (alpha-[(11)C]MTrp) has been proposed as an index of 5
      HT synthesis capacity. The authors measured brain regional alpha-[(11)C]MTrp
      trapping with positron emission tomography in medication-free subjects with
      borderline personality disorder (N=13) and a healthy comparison group (N=11).
      Impulsivity was assessed by using a laboratory measure of behavioral
      disinhibition, go/no-go commission errors. RESULTS: Compared to healthy men, the
      men with borderline personality disorder had significantly lower alpha
      [(11)C]MTrp trapping in corticostriatal sites, including the medial frontal
      gyrus, anterior cingulate gyrus, superior temporal gyrus, and corpus striatum. In
      the women with borderline personality disorder, significantly lower alpha
      [(11)C]MTrp trapping was seen in fewer regions, but in both men and women,
      negative correlations with impulsivity scores were identified in the medial
      frontal gyrus, anterior cingulate gyrus, temporal gyrus, and striatum.
      CONCLUSIONS: Low 5-HT synthesis capacity in corticostriatal pathways may
      contribute to the development of impulsive behaviors in persons with borderline
      personality disorder.

PMID- 11329402
TI  - Hypochondriacal patients' appraisal of health and physical risks.
AB  - OBJECTIVE: The authors' goal was to assess the degree to which hypochondriasis is
      accompanied by a heightened sense of risk of disease and other physical hazards.
      METHOD: Fifty-six patients meeting DSM-III-R criteria for hypochondriasis were
      compared with 127 nonhypochondriacal patients from the same primary care setting.
      Both groups completed a self-report questionnaire assessing the degree to which
      they felt at risk of developing various medical diseases or being subject to
      injury from accidents or criminal assault. RESULTS: Both groups of patients
      exhibited an optimistic bias in that they considered themselves to be less at
      risk than others of their age and sex. However, the hypochondriacal group had a
      significantly higher total risk score than did the nonhypochondriacal group. In
      large part, this intergroup difference was the result of the hypochondriacal
      patients' perception that they were likely to develop various diseases. The
      hypochondriacal group did not score significantly higher than the comparison
      group in estimating their risk of succumbing to accidents and criminal
      victimization. Perceived risk was significantly associated with the self-reported
      tendency to amplify benign bodily sensations. CONCLUSIONS: An exaggerated
      appraisal of risk, jeopardy, and vulnerability to disease may be part of the
      cognitive distortion seen in hypochondriasis. If this is confirmed, cognitive and
      behavioral therapies for hypochondriasis may need to include a focus on these
      patients' understanding and appraisal of risk.

PMID- 11329403
TI  - Posttraumatic stress and depressive reactions among Nicaraguan adolescents after
      hurricane Mitch.
AB  - OBJECTIVE: This study determined the severity of posttraumatic stress and
      depressive reactions among Nicaraguan adolescents after Hurricane Mitch and the
      relationship of these reactions to objective and subjective features of hurricane
      exposure, death of a family member, forced relocation, and thoughts of revenge.
      METHOD: Six months after the hurricane, 158 adolescents from three differentially
      exposed cities were evaluated by using a hurricane exposure questionnaire, the
      Child Posttraumatic Stress Disorder Reaction Index, and the Depression Self
      Rating SCALE: RESULTS: Severe levels of posttraumatic stress and depressive
      reactions were found among adolescents in the two most heavily affected cities.
      Severity of posttraumatic stress and depressive reactions and features of
      objective hurricane-related experiences followed a "dose-of-exposure" pattern
      that was congruent with the rates of death and destruction across cities. Level
      of impact (city), objective and subjective features, and thoughts of revenge
      accounted for 68% of the variance in severity of posttraumatic stress reaction.
      Severity of posttraumatic stress reaction, death of a family member, and sex
      accounted for 59% of the variance in severity of depression. CONCLUSIONS: After a
      category 5 hurricane, adolescents in heavily affected areas with extreme
      objective and subjective hurricane-related traumatic features of exposure
      experience severe and chronic posttraumatic stress and comorbid depressive
      reactions. The recovery of the severely affected Nicaraguan adolescents is vital
      to the social and economic recovery of a country ravaged by years of political
      violence and poverty. These findings strongly indicate the need to incorporate
      public mental health approaches, including systematic screening and trauma/grief
      focused interventions, within a comprehensive disaster recovery program.

PMID- 11329404
TI  - Traumatic distress among support-seeking female victims of stalking.
AB  - OBJECTIVE: The authors examined the nature and prevalence of stalking behaviors,
      victims' coping responses, and the psychomedical impact of stalking on its
      victims. METHOD: Widely accepted self-report measures, including the 12-item
      General Health Questionnaire and the Impact of Event Scale, were used to assess
      characteristics of the stalking history and its outcome in terms of general
      psychomedical distress and posttraumatic stress in a community study group of 201
      female stalking victims. RESULTS: The majority of the victims had undergone
      multiple forms of harassment, including threats of violence in 74% (N=148) and
      actual violence in 55% (N=111). More than half of the victims met the criterion
      for clinically significant pathology on the General Health QUESTIONNAIRE:
      Stalking often yielded substantial posttraumatic stress symptoms, commensurate
      with levels found in other studies of traumatized subjects. CONCLUSIONS: Support
      seeking female stalking victims experience pervasive and persistent threat and
      intrusion; these experiences lead to high levels of psychological morbidity.

PMID- 11329405
TI  - Cognitive correlates of obsessive and compulsive symptoms in Huntington's
      disease.
AB  - OBJECTIVE: The authors' goal was to examine the frequency and type of obsessive
      and compulsive symptoms in Huntington's disease. METHOD: The Yale-Brown Obsessive
      Compulsive Scale was used to assess obsessive and compulsive symptoms in 27
      patients with Huntington's disease. The neuropsychological test performance of
      the 14 patients with at least one obsessive symptom and the seven patients with
      at least one compulsive symptom was compared with the performance of the patients
      without such symptoms. RESULTS: More than half of the patients with Huntington's
      disease endorsed obsessive or compulsive symptoms on the Yale-Brown scale.
      Patients with obsessive or compulsive symptoms showed significantly greater
      impairment on neuropsychological tests measuring executive function than those
      without such symptoms. CONCLUSIONS: Basal ganglia pathology in Huntington's
      disease may contribute to production of obsessive and compulsive symptoms and to
      executive performance deficits in these patients.

PMID- 11329406
TI  - Association of short-term response to haloperidol treatment with a polymorphism
      in the dopamine D(2) receptor gene.
AB  - OBJECTIVE: Pharmacogenetic influences on therapeutic response to neuroleptic
      treatment are poorly understood. This study investigates the association of
      response to short-term haloperidol treatment with a Taq I polymorphism in the
      DRD2 gene. METHOD: Fifty-seven patients with acute psychosis were treated with
      haloperidol for up to 28 days. Improvement and response were measured by using
      the Positive and Negative Syndrome SCALE: Forty-one patients were homozygous for
      allele 2, and 16 were heterozygous. RESULTS: Heterozygous patients showed a
      greater improvement in positive, but not in negative, symptoms on all treatment
      days than patients homozygous for allele 2. Differences in improvement of
      positive symptoms reached statistical significance on days 14, 21, and 28. On
      treatment day 14, 10 (62.5%) of 16 heterozygous patients had at least 50%
      improvement of positive symptoms, compared with 11 (28.9%) of 38 homozygous
      patients. CONCLUSIONS: These results support the hypothesis that genetic
      variations in the DRD2 gene may influence the individual response to
      antipsychotics.

PMID- 11329407
TI  - Sustained-release bupropion for selective serotonin reuptake inhibitor-induced
      sexual dysfunction: a randomized, double-blind, placebo-controlled, parallel
      group study.
AB  - OBJECTIVE: The authors compared low-dose sustained-release bupropion with placebo
      for sexual dysfunction induced by selective serotonin reuptake inhibitors
      (SSRIs). METHOD: Thirty adults who had received SSRIs for at least 6 weeks, who
      were euthymic, and who had sexual dysfunction as determined by a total score
      greater than 19 out of a possible 30 on the Arizona Sexual Experience Scale were
      randomly assigned to receive either 150 mg/day of sustained-release bupropion or
      placebo at 6:00 p.m. for 3 weeks. RESULTS: There were no significant differences
      between the sustained-release bupropion and placebo groups as measured by change
      in Arizona Sexual Experiences Scale or Hamilton Depression Rating Scale scores or
      side effects. CONCLUSIONS: Future studies should compare higher doses of
      bupropion for treating sexual dysfunction and should include a greater number of
      subjects.

PMID- 11329408
TI  - Creating a peaceful school learning environment: a controlled study of an
      elementary school intervention to reduce violence.
AB  - OBJECTIVE: The impact of a manual-based antiviolence program on the learning
      climate in an elementary school over 4 years was compared with the outcome in a
      control school. METHOD: The two schools were matched for demographic
      characteristics. The intervention in the experimental school was based on zero
      tolerance for bullying; the control school received only regular psychiatric
      consultation. Disciplinary and academic achievement data were collected in both
      schools. RESULTS: The experimental school showed significant reductions in
      discipline referrals and increases in scores on standardized academic achievement
      measures. CONCLUSIONS: A low-cost antiviolence intervention that does not focus
      on individual pathology or interfere with the educational process may improve the
      learning environment in elementary schools.

PMID- 11329409
TI  - A systematic investigation of 16 cases of neonaticide.
AB  - OBJECTIVE: Neonaticide, or infant murder on the day of birth, is often preceded
      by denial of pregnancy. The preponderance of case reports of neonaticide
      describes a pattern of pregnancy denial, dissociation, and ego disorganization.
      The author systematically investigated the clinical characteristics of 16 women
      charged with homicide in the United States after alleged neonaticides. METHOD:
      The women received a psychiatric evaluation and were administered the
      Dissociative Experiences SCALE: RESULTS: Nearly all of the women reported similar
      precipitants and symptoms, including depersonalization, dissociative
      hallucinations, and intermittent amnesia at delivery. CONCLUSIONS: The
      characteristics of the women in the study were similar to those reported in the
      literature on neonaticide. The existence of this common pattern suggests that
      treatment strategies can be designed for women at risk for neonaticide.

PMID- 11329410
TI  - Sweet taste preference as a risk factor for alcohol dependence.
AB  - OBJECTIVE: Previous research has found that alcoholics have a greater preference
      for sweet solutions than comparison subjects. This study tested the hypothesis
      that preference for sweet solutions is a marker for alcoholism risk. METHOD: A
      total of 122 nonalcoholic subjects (59 men) participated. Fifty-eight subjects
      had a paternal history of alcoholism, and 64 did not. Each subject rated a series
      of sucrose solutions for intensity of sweetness and degree of preference.
      RESULTS: Subjects were able to rate accurately the relative intensity of
      sweetness in the sucrose solutions. Both subjects with and those without a
      paternal history of alcoholism preferred a 0.42-M sucrose solution, irrespective
      of gender. CONCLUSIONS: This study failed to support the hypothesis that sweet
      preference is a marker of alcoholism risk. The sweet preference observed
      previously among alcoholics may be a consequence of chronic alcohol consumption
      or other factors associated with heavy drinking.

PMID- 11329411
TI  - Recurrent depression with vagus nerve stimulation.

PMID- 11329412
TI  - Clozapine and weight gain.

PMID- 11329413
TI  - Quetiapine and leukopenia.

PMID- 11329414
TI  - Adderall for obsessive-compulsive disorder.

PMID- 11329415
TI  - Acute visual loss after thioridazine overdose.

PMID- 11329416
TI  - Recurrence of affective disorder.

PMID- 11329417
TI  - Mirtazapine for neuroleptic-induced akathisia.

PMID- 11329418
TI  - Boundary of amygdala and hippocampus.

PMID- 11329420
TI  - Newton's psychosis.

PMID- 11329422
TI  - Domestic abuse and religion.

PMID- 11329424
TI  - Platelet function and sertraline.

PMID- 11329428
TI  - High serum cholesterol and suicide risk.

PMID- 11329430
TI  - Olanzapine and negative and positive symptoms.

PMID- 11329442
TI  - High-quality, cost-effective strategy for detection of autoantibodies to
      extractable nuclear antigens.
AB  - We evaluated methods for the detection of autoantibodies to extractable nuclear
      antigens (ENAs) to determine the strategy that yielded the most cost effective
      and clinically meaningful result. We prospectively compared
      counterimmunoelectrophoresis (CIEP) with and without serum prediffusion (SPD) and
      found that SPD significantly improved the quality of precipitation lines. This
      resulted in a decreased requirement for repeat testing and, consequently, was
      associated with a significant decrease in reagent costs and specimen turnaround
      time. We also retrospectively compared reactivity by CIEP, CIEP plus SPD, enzyme
      linked immunosorbent assay (ELISA), and line immunoassay (LIA) of 52 serum
      samples that were previously determined to be positive for ENAs, and we
      correlated the results with clinical diagnoses. There was significant agreement
      among CIEP, CIEP plus SPD, ELISA, and LIA for the detection of anti-SS-A, anti-SS
      B and anti-RNP. In general, CIEP, CIEP plus SPD, and LIA correlated better with
      the clinical diagnoses than ELISA, even though ELISA detected anti-ENAs more
      often than the other methods. CIEP plus SPD is therefore the most cost effective
      method for the identification of clinically meaningful ENAs. Based on our
      experience, we now screen for ENAs by CIEP, and positive samples are then typed
      by CIEP plus SPD. Samples that are difficult to interpret are then further
      assessed by an alternative method.

PMID- 11329443
TI  - Development of an immunoglobulin M (IgM) capture enzyme-linked immunosorbent
      assay for detection of equine and swine IgM antibodies to vesicular stomatitis
      virus.
AB  - An immunoglobulin M (IgM) capture enzyme-linked immunosorbent assay (MC-ELISA)
      was developed for the detection of primary infection of vesicular stomatitis
      virus (VSV) in equine and swine sera. The test was based on the use of
      biotinylated sheep antibodies against equine or swine IgM molecules bound to a
      streptavidin-coated ELISA plate. The captured IgM antibodies were detected by
      application of antigens prepared from the New Jersey and the Indiana VSV
      serotypes (VSV-NJ and VSV-IN, respectively) and mouse polyclonal antibodies
      against VSV-NJ and VSV-IN. The MC-ELISA was compared to a competitive ELISA (C
      ELISA) and the standard microtiter serum neutralization (MTSN) assay by testing
      serum samples from horses and pigs experimentally infected with VSV-NJ or VSV-IN.
      The MC-ELISA detected specific homologous IgM antibodies from equine and swine
      sera as early as 5 and 4 days postinfection (DPI), respectively, and as late as
      35 DPI. The MTSN test also detected antibodies as early as 5 DPI and as late as
      160 DPI. In a similar fashion, the C-ELISA detected antibodies from 6 to 7 DPI
      and as late as 160 DPI. These results demonstrated that the MC-ELISA is a useful
      test for serodiagnosis of primary VSV infection in horses and pigs.

PMID- 11329444
TI  - Development of a novel in vitro assay (ALS assay) for evaluation of vaccine
      induced antibody secretion from circulating mucosal lymphocytes.
AB  - We describe here a novel method for measuring in vitro antibody secretion from
      the tissue culture of human B lymphocytes in peripheral blood mononuclear cells
      (PBMC) after oral vaccination with a killed cholera vaccine. Enzyme-linked
      immunosorbent assay (ELISA) titers of the antibody secreted in the cell
      supernatant were determined. The validation results demonstrated that human PBMC
      remained viable and continued to secrete antibodies (total immunoglobulin A [IgA]
      and IgG) for up to 4 days of incubation at 37 degrees C with 5% CO(2) in cell
      cultures. The secreted antibody concentration correlated positively with the PBMC
      concentration and incubation time in the tissue culture and correlated negatively
      with the storage time of the whole blood at room temperature. In vitro assay of
      secreting antibody in the lymphocyte supernatant (i.e., the ALS assay) is capable
      of the detecting specific antibody response after oral vaccination with a killed
      whole-cell-plus-B-subunit cholera vaccine (WC-B) in healthy adults in a phase I
      clinical trial. Postimmunization PBMC secreted antibodies to cholera toxin in the
      cell supernatants. Antibody production did not require any in vitro antigen
      stimulation. In the ALS assay, antigen-specific antibody titers of prevaccination
      samples were barely detectable, whereas serum antitoxin ELISA titers in
      background of prevaccine samples were significantly higher than the ALS titers.
      We conclude that, without any in vitro antigen stimulation after vaccination,
      PBMC secrete antibodies into the supernatants in the ALS assay. This assay can
      quantitatively measure the antigen-specific antibody production from the PBMC
      culture in postvaccination blood samples.

PMID- 11329446
TI  - Evaluation of a latex agglutination kit (Virogen Rotatest) for detection of
      bovine rotavirus in fecal samples.
AB  - The performance of the Virogen Rotatest latex agglutination test (LAT) was
      evaluated for detection of bovine rotavirus antigen. Sixty-three fecal samples
      from diarrheic calves were collected from November 1999 to May 2000 and screened
      by LAT, the Rotazyme II enzyme-linked immunosorbent assay (ELISA), and virus
      isolation (VI) followed by an anti-rotavirus fluorescent-antibody (FA) test to
      detect the presence of group A rotavirus antigen. Of the 63 samples screened by
      VI-FA, 33 (58%) tested positive for rotavirus antigen. When the results from the
      LAT were compared to those from VI-FA, the "gold standard" for detection of
      bovine rotavirus in fecal samples, the sensitivity and specificity were found to
      be 87.8 and 73.3%, respectively. Latex agglutination compared with ELISA (the
      reference method) showed 100% sensitivity and 96.3% specificity, and when ELISA
      was compared with VI, the sensitivity was 84.8% and the specificity was 73.3%.
      Latex agglutination is easy to perform in a short time and does not require
      expensive equipment or skilled personnel, and the reagents have long shelf lives.
      These factors make the LAT suitable and highly efficient for use in a clinical
      laboratory as a rapid screening test for bovine rotavirus.

PMID- 11329445
TI  - Type 1 fimbriation and its phase switching in diarrheagenic Escherichia coli
      strains.
AB  - Type 1 fimbriae can be expressed by most Escherichia coli strains and mediate
      mannose-sensitive (MS) adherence to mammalian epithelial cells. However, the role
      of type 1 fimbriae in enteric pathogenesis has been unclear. Expression of type 1
      fimbriae in E. coli is phase variable and is associated with the inversion of a
      short DNA element (fim switch). Forty-six strains of diarrheagenic E. coli were
      examined for the expression of type 1 fimbriae. Only four of these strains were
      originally type 1 fimbriated. Seventeen strains, originally nonfimbriated,
      expressed type 1 fimbriae in association with off-to-on inversion of the fim
      switch, after serial passages in static culture. The switching frequencies of
      these strains, from fimbriate to nonfimbriate, were greater than that of the
      laboratory strain E. coli K-12. None of the 16 strains of serovar O157:H7 or
      O157:H(-) expressed type 1 fimbriae after serial passages in static culture. The
      nucleotide sequence analysis of the fim switch region revealed that all of the
      O157:H7 and O157:H(-) strains had a 16-bp deletion in the invertible element, and
      the fim switch was locked in the "off" orientation. The results suggest that
      expression of type 1 fimbriae may be regulated differently in different E. coli
      pathogens causing enteric infections.

PMID- 11329447
TI  - PCR-based method for isolation and detection of Chlamydia pneumoniae DNA in
      cerebrospinal fluids.
AB  - Since current studies indicate the possible involvement of Chlamydia pneumoniae
      in the pathogenesis of multiple sclerosis (MS), demonstration of C. pneumoniae in
      the cerebrospinal fluid (CSF) of patients with MS is highly desirable. However,
      there is controversy concerning the detection of C. pneumoniae in CSFs from MS
      patients due to the lack of a standard protocol for extraction and detection of
      C. pneumoniae DNA. In this regard, we attempted to establish a highly effective
      extraction protocol for C. pneumoniae DNA from CSFs utilizing a commercial kit
      and a PCR detection method. The extraction and PCR detection protocol established
      in this study succeeded in detecting as few as 20 C. pneumoniae organisms in 200
      microl of mock CSF. The use of this protocol to detect C. pneumoniae DNA in CSFs
      revealed that 68% of CSF samples obtained from patients with MS were positive (11
      out of 16 samples) for chlamydia DNA. Thus, the protocol established here is
      sensitive enough to detect chlamydia DNA from CSFs and can be used by other
      laboratories for evaluation of the presence of chlamydiae in CSFs because the
      protocol is based on the use of a commercial kit.

PMID- 11329448
TI  - Internal transcribed spacer regions of rRNA genes of Pneumocystis carinii from
      monkeys.
AB  - Analysis of sequence variations among isolates of Pneumocystis carinii f. sp.
      macacae from 14 Indian rhesus monkeys (Macaca mulatta) at the internal
      transcribed spacer (ITS) regions of the nuclear rRNA gene was undertaken. Like
      those from P. carinii f. sp. hominis, the ITS sequences from various P. carinii
      f. sp. macacae isolates were not identical. Two major types of sequences were
      found. One type of sequence was shared by 13 isolates. These 13 sequences were
      homologous but not identical. Variations were found at 13 of the 180 positions in
      the ITS1 region and 28 of the 221 positions in the ITS2 region. These sequence
      variations were not random but exhibited definite patterns when the sequences
      were aligned. According to this sequence variation, ITS1 sequences were
      classified into three types and ITS2 sequences were classified into five types.
      The remaining specimen had ITS1 and ITS2 sequences substantially different from
      the others. Although some specimens had the same ITS1 or ITS2 sequence, all 14
      samples exhibited a unique whole ITS sequence (ITS1 plus ITS2). The 5.8S rRNA
      gene sequences were also analyzed, and only two types of sequences that differ by
      only one base were found. Unlike P. carinii f. sp. hominis infections in humans,
      none of the monkey lung specimens examined in this study were found to be
      infected by more than one type of P. carinii f. sp. macacae. These results offer
      insights into the genetic differences between P. carinii organisms which infect
      distinct species.

PMID- 11329449
TI  - Detection of heme-binding proteins in epidemic strains of Burkholderia cepacia.
AB  - A panel of 30 previously characterized strains representing five genomovars from
      the Burkholderia cepacia complex (E. Mahenthiralingam, T. Coenye, J. W. Chung, D.
      P. Speert, J. R. W. Govan, P. Taylor, and P. Vandamme, J. Clin. Microbiol. 38:910
      -913, 2000) were examined for their iron protoporphyrin IX-binding ability. These
      included B. cepacia genomovars I and III and B. stabilis (formerly B. cepacia
      genomovar IV), B. multivorans (formerly B. cepacia genomovar II), and B.
      vietnamiensis (formerly B. cepacia genomovar V). Cells were exposed to micro-oxo
      bisheme of iron protoporphyrin IX (micro-oxo dimers) and examined by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis under nonreducing,
      nondenaturing conditions for the presence of heme-binding proteins using
      tetramethylbenzidine-H(2)O(2) staining. Seven of the 30 strains, each belonging
      to B. cepacia genomovar III and designated epidemic (in possessing the B. cepacia
      epidemic strain marker), expressed a 96- to 100-kDa heme-binding protein which
      was located in the outer membrane. The heme-binding protein of B. cepacia
      genomovar III epidemic strain C5424 bound iron(III) protoporphyrin IX in both the
      monomeric and micro-oxo bisheme forms. Cells of all strains grown on Columbia
      agar bound iron protoporphyrin IX in the micro-oxo bisheme (dimeric) form. There
      were no statistical differences between the five genomovars, or those possessing
      the heme-binding protein, in their micro-oxo bisheme-binding ability. Possession
      of the outer membrane heme-binding protein may be a pathogenicity trait in
      enabling the bacterium to withstand oxidative stresses in inflammatory exudates
      in the lung and may aid identification of invasive epidemic strains of B.
      cepacia.

PMID- 11329450
TI  - Peptidoglycan and lipoteichoic acid modify monocyte phenotype in human whole
      blood.
AB  - We examined the influence of the gram-positive cell wall products peptidoglycan
      (PepG) and lipoteichoic acid (LTA), compared to lipopolysaccharide (LPS), on the
      monocyte expression of receptors involved in antigen presentation (HLA-DR, B7.1,
      and B7.2), cell adhesion (intercellular adhesion molecule-1 [ICAM-1] and
      lymphocyte function associated antigen-3 [LFA-3]), phagocytosis (Fc gamma RI),
      and cell activation (CD14). We also evaluated possible influences of the
      immunosuppressive drugs cyclosporine A, tacrolimus, and sirolimus on the
      expression of these receptors. Pretreatment of whole blood for 4 h with the
      immunosuppressive drugs did not influence the expression of the surface receptors
      in normal or stimulated blood. Stimulation with both PepG and LTA caused
      significant up-regulation of the surface expression of ICAM-1 and HLA-DR on whole
      blood monocytes, similar to that obtained with LPS, whereas B7.1, B7.2, LFA-3,
      and Fc gamma RI were not modulated. PepG and LTA also caused increased expression
      of CD14, whereas LPS down-regulated this molecule. In contrast, we did not detect
      any significant influence of any of the bacterial products on the plasma
      concentration of soluble CD14. We hypothesized that the increased expression of
      surface CD14 in blood stimulated with PepG would prime for cellular activation by
      LPS. Indeed, we show that PepG and the partial PepG structure muramyl dipeptide
      acted in synergy with LPS to cause the release of tumor necrosis factor-alpha.
      The results suggest that PepG and LPS provoke partly different responses on
      monocyte phenotype and that CD14 may play different roles in the innate response
      to gram-positive and gram-negative bacteria.

PMID- 11329451
TI  - Biological properties of lipid A isolated from Flavobacterium meningosepticum.
AB  - The biological properties of the lipid A from Flavobacterium meningosepticum,
      which we recently isolated and whose complete chemical structure has been
      determined (H. Kato, T. Iida, Y. Haishima, A. Tanaka, and K. Tanamoto. J.
      Bacteriol. 180:3891--3899, 1998), were studied. The lipid A exhibited generally
      moderate activity compared to Salmonella enterica subsp. enterica serovar abortus
      equi lipopolysaccharide (LPS) used as a control in the assay systems tested;
      lethal toxicity in galactosamine-sensitized mice, mitogenicity in mouse spleen
      cells, induction of tumor necrosis factor alpha (TNF-alpha) release from mouse
      peritoneal macrophages and J774-1 mouse macrophage-like and human THP-1 line
      cells, nitric oxide induction activity from J774-1 cells, and Limulus gelation
      activity. The moderate activity of the F. meningosepticum lipid A may be
      explained by its unique fatty acid composition and the lack of a phosphate group
      in position 4'. It is noteworthy that the lipid A apparently induced TNF-alpha
      release from peritoneal macrophages in LPS-unresponsive C3H/HeJ mice and that the
      activation was suppressed by the LPS-specific antagonist, succinylated lipid A
      precursor. Significant splenocyte mitogenicity in C3H/HeJ mice was also observed
      with the lipid A. Taken together with the previous results concerning
      Porphyromonas gingivalis lipid A, which has a high level of structural similarity
      to the lipid A of F. meningosepticum, and the induction of TNF-alpha release in
      macrophages from C3H/HeJ mice, the lipid A of F. meningosepticum, which has novel
      fatty acids, may possibly play an role for the activation of C3H/HeJ macrophages.

PMID- 11329452
TI  - Chromogenic assay measuring opsonophagocytic killing capacities of
      antipneumococcal antisera.
AB  - Assays measuring opsonophagocytic killing capacity of immune sera are good
      surrogate assays for assessing pneumococcal vaccine responses, but they are
      tedious to perform primarily because the enumeration of surviving bacteria
      requires the counting of individual bacterial colonies. To overcome this
      limitation, we have developed a simple and rapid chromogenic assay for estimating
      the number of surviving bacteria. In this method, the conventional
      opsonophagocytic killing assays were performed in microtiter wells with
      differentiated HL-60 cells as phagocytes. At the end of the assay the reaction
      mixture was cultured for an additional 4.5 h to increase the number of bacteria.
      After the short culture, XTT (3,3'-[1[(phenylamino)carbonyl]-3,4-tetrazolium]
      bis[4-methoxy-6-nitro] benzene sulfonic acid hydrate) and coenzyme Q were added
      to the wells and the optical density at 450 nm was measured. Our study shows that
      changes in the optical density were proportional to the number of CFU of live
      bacteria in the wells. Also, the number of bacteria at the end of the 4.5-h
      culture was found to be proportional to the original number of bacteria in the
      wells. When the performance of the chromogenic assay was evaluated by measuring
      the opsonizing titers of Streptococcus pneumoniae serotypes 6B and 19F, the
      sensitivity and precision of the new method were similar to those of the
      conventional opsonization assay employing the colony counting method.
      Furthermore, the results of this chromogenic assay obtained with 33 human sera
      correlate well with those obtained with the conventional colony counting method
      (R > 0.90) for the two serotypes (6B and 19F). Thus, this simple chromogenic
      assay would be useful in rapidly measuring the capacities of antisera to opsonize
      pneumococci.

PMID- 11329453
TI  - Western immunoblotting with five Treponema pallidum recombinant antigens for
      serologic diagnosis of syphilis.
AB  - Five immunodominant Treponema pallidum recombinant polypeptides (rTpN47, rTmpA,
      rTpN37, rTpN17, and rTpN15) were blotted onto strips, and 450 sera (200 from
      blood donors, 200 from syphilis patients, and 50 potentially cross-reactive) were
      tested to evaluate the diagnostic performance of recombinant Western blotting
      (recWB) in comparison with in-house whole-cell lysate antigen-based
      immunoblotting (wclWB) and T. pallidum hemagglutination (MHA-TP) for the
      laboratory diagnosis of syphilis. None of the serum specimens from blood donors
      or from potential cross-reactors gave a positive result when evaluated by recWB,
      wclWB, or MHA-TP. The evaluation of the immunoglobulin G immune response by recWB
      in sera from patients with different stages of syphilis showed that rTmpA was the
      most frequently identified antigen (95%), whereas only 41% of the specimens were
      reactive to rTpN37. The remaining recombinant polypeptides were recognized as
      follows: rTpN47, 92.5%; rTpN17, 89.5%; and rTpN15, 67.5%. The agreement between
      recWB and MHA-TP was 95.0% (100% with sera from patients with latent and late
      disease), and the concordance between wclWB and MHA-TP was 92.0%. The overall
      concordance between recWB and wclWB was 97.5% (100% with sera from patients with
      secondary and late syphilis and 94.6 and 98.6% with sera from patients with
      primary and latent syphilis, respectively). The overall sensitivity of recWB was
      98.8% and the specificity was 97.1% with MHA-TP as the reference method. These
      values for sensitivity and specificity were slightly superior to those calculated
      for wclWB (sensitivity, 97.1%, and specificity, 96.1%). With wclWB as the
      standard test, the sensitivity and specificity of recWB were 98.9 and 99.3%,
      respectively. These findings suggest that the five recombinant polypeptides used
      in this study could be used as substitutes for the whole-cell lysate T. pallidum
      antigens and that this newly developed recWB test is a good, easy-to-use
      confirmatory method for the detection of syphilis antibodies in serum.

PMID- 11329454
TI  - Modified immunogenicity of a mucosally administered antigen.
AB  - Streptococcus mutans is present in the saliva of most individuals and is modified
      by salivary components bound to the cells. These saliva-bound S. mutans are
      swallowed, exposed to high levels of acidity in the stomach, and presented to the
      common mucosal immune system. Much effort has been directed to identifying the
      specific S. mutans antigens that the mucosal immune responses are directed
      against. However, little is known about the host-altered antigenic determinants
      that the mucosal immune system recognizes. The immunogenicity of gastrically
      intubated untreated S. mutans cells, cells coated with whole human saliva, cells
      treated with HCl (pH 2.0), and saliva-coated and acid-treated cells in mice was
      investigated. Saliva and serum samples were assayed by enzyme linked
      immunosorbent assay for immunoglobulin A (IgA) and IgG antibodies, respectively,
      against the untreated or treated S. mutans cells. In general, the levels of
      salivary IgA and serum IgG antibodies to the antigen against which the mice were
      immunized were significantly higher (P < or = 0.05). In addition, human saliva
      and serum samples from 12 subjects were assayed for naturally occurring antibody
      against the untreated or treated S. mutans cells. In every case, significantly
      higher reactivity was directed against the saliva-coated and acid-treated cells
      followed by the saliva-coated S. mutans. These results provide evidence for the
      altered immunogenicity of swallowed S. mutans in humans by coating native S.
      mutans antigens with salivary components and/or denaturing surface S. mutans
      antigens in the acidic environment of the stomach, which would lead to an immune
      response to modified S. mutans determinants and not to native S. mutans antigens.

PMID- 11329455
TI  - Induction of mucosal immune response after intranasal or oral inoculation of mice
      with Lactococcus lactis producing bovine beta-lactoglobulin.
AB  - The bovine beta-lactoglobulin (BLG) is a major cow's milk allergen. Here, we
      evaluated the immune response against BLG induced in mice, using the organism
      Lactococcus lactis, which has GRAS ("generally regarded as safe") status, as a
      delivery vehicle. The cDNA of the blg gene, encoding BLG, was expressed and
      engineered for either intra- or extracellular expression in L. lactis. Using a
      constitutive promoter, the yield of intracellular recombinant BLG (rBLG) was
      about 20 ng per ml of culture. To increase the quantity of rBLG, the nisin
      inducible expression system was used to produce rBLG in the cytoplasmic and
      extracellular locations. Although the majority of rBLG remained in the cytoplasm,
      the highest yield (2 microg per ml of culture) was obtained with a secreting
      strain that encodes a fusion between a lactococcal signal peptide and rBLG.
      Whatever the expression system, the rBLG is produced mostly in a soluble,
      intracellular, and denatured form. The BLG-producing strains were then
      administered either orally or intranasally to mice, and the immune response to
      BLG was examined. Specific anti-BLG immunoglobulin A (IgA) antibodies were
      detected 3 weeks after the immunization protocol in the feces of mice immunized
      with the secreting lactococcal strain. Specific anti-BLG IgA detected in mice
      immunized with lactococci was higher than that obtained in mice immunized with
      the same quantity of pure BLG. No specific anti-BLG IgE, IgA, IgG1, or IgG2a was
      detected in sera of mice. These recombinant lactococcal strains constitute good
      vehicles to induce a mucosal immune response to a model allergen and to better
      understand the mechanism of allergy induced by BLG.

PMID- 11329456
TI  - Comparison of immulite with vidas for detection of infection in a low-prevalence
      population of pregnant women in The Netherlands.
AB  - A comparative evaluation of the Vidas system (bioMerieux, Marcy l'Etoile, France)
      and the Immulite System (Diagnostic Products Corporation) was performed using 500
      prospectively collected serum samples. As part of a routine antenatal screening
      program, these samples were tested for hepatitis B surface antigen, and
      immunoglobulin G (IgG) and IgM antibodies to Toxoplasma gondii and rubella virus.
      The overall agreement between the two assay systems ranged from 98.0 to 99.8%.
      After discrepancy analysis the outcome in terms of relative sensitivity and
      specificity varied from 97.5 to 100%.

PMID- 11329457
TI  - Influence of patient age on Streptococcus pneumoniae serotypes causing invasive
      disease.
AB  - All clinical S. pneumoniae specimens isolated from patients with invasive or
      sterile-site infections admitted to one regional general hospital in southern
      Chile were collected during a 5-year period (February 1994 to September 1999). A
      total of 247 strains belonging to 50 serotypes were isolated in this survey: 69
      in patients under 5 years of age, 129 in patients 5 to 64 years old, and 49 from
      patients 65 years and older. Eight serotypes were identified in all age groups,
      while all other serotypes were found exclusively in one age group or in patients
      over 4 years of age. Serotype 3 was never found in patients under 5 years old,
      and serotype 14 was not found in patients >64 years of age. There was no
      difference in the serotypes causing infection in each one of the 5 years of the
      survey. Our results suggest that both bacterial virulence factors and host
      factors play an important role in the selection of S. pneumoniae serotypes
      causing invasive infection. Possible host factors include age-related differences
      in the immune response. Comparative studies with other areas of the world may
      help to further understanding of our observations in southern Chile.

PMID- 11329458
TI  - Intra- and interlaboratory variabilities of results obtained with the Quantiplex
      human immunodeficiency virus type 1 RNA bDNA assay, version 3.0.
AB  - Normal assay variation associated with bDNA tests for human immunodeficiency
      virus type 1 (HIV-1) RNA performed at two laboratories with different levels of
      test experience was investigated. Two 5-ml aliquots of blood in EDTA tubes were
      collected from each patient for whom the HIV-1 bDNA test was ordered. Blood was
      stored for no more than 4 h at room temperature prior to plasma separation.
      Plasma was stored at -70 degrees C until transported to the Central Pennsylvania
      Alliance Laboratory (CPAL; York, Pa.) and to the Hershey Medical Center (Hershey,
      Pa.) on dry ice. Samples were stored at < or =-70 degrees C at both laboratories
      prior to testing. Pools of negative (donor), low-HIV-1-RNA-positive, and high-HIV
      1-RNA-positive plasma samples were also repeatedly tested at CPAL to determine
      both intra- and interrun variation. From 11 August 1999 until 14 September 2000,
      448 patient specimens were analyzed in parallel at CPAL and Hershey. From 206
      samples with results of > or =1,000 copies/ml at CPAL, 148 (72%) of the results
      varied by < or =0.20 log(10) when tested at Hershey and none varied by >0.50
      log(10). However, of 242 specimens with results of <1,000 copies/ml at CPAL, 11
      (5%) of the results varied by >0.50 log(10) when tested at Hershey. Of 38
      aliquots of HIV-1 RNA pool negative samples included in 13 CPAL bDNA runs, 37
      (97%) gave results of <50 copies/ml and 1 (3%) gave a result of 114 copies/ml.
      Low-positive HIV-1 RNA pool intrarun variation ranged from 0.06 to 0.26 log(10)
      while the maximum interrun variation was 0.52 log(10). High-positive HIV-1 RNA
      pool intrarun variation ranged from 0.04 to 0.32 log(10), while the maximum
      interrun variation was 0.55 log(10). In our patient population, a change in bDNA
      HIV-1 RNA results of < or =0.50 log(10) over time most likely represents normal
      laboratory test variation. However, a change of >0.50 log(10), especially if the
      results are >1,000 copies/ml, is likely to be significant.

PMID- 11329459
TI  - New automated immunoassay measuring immunoglobulin A antigliadin antibodies for
      prediction of celiac disease in childhood.
AB  - The prevalence of celiac disease (CD) in Sweden is about 4 cases per 1,000
      people. Screening for CD with serological tests indicates similar high
      prevalences in many other countries. Between 1 November 1992 and 30 April 1995,
      133 children (9 months to 16.7 years of age) with suspected CD were studied. The
      predictive value (PV) of immunoglobulin A antigliadin antibodies (IgA-AGA) in the
      serum as assayed with two new commercial automated immunoassays--the Pharmacia
      CAP System Gliadin IgA FEIA (CAP) and the UNICAP-100 (UNICAP)--and with three "in
      house" methods was evaluated using assessment of the small intestinal mucosa
      morphology as the "gold standard." All serum samples were analyzed for total
      serum IgA. At presentation the diagnostic sensitivities and specificities of the
      different tests varied from 0.72 to 0.88 and 0.67 to 0.87, respectively. All
      methods showed a higher sensitivity for CD in younger children. The area under
      each assay's receiver operating characteristic curve was calculated and varied
      between 0.82 and 0.89. The positive and negative PVs for the CAP and UNICAP,
      which were assays with a high sensitivity and a high specificity, respectively,
      were estimated. In the clinically selected population (prevalence of CD, 1 in 3)
      the positive PV was about 55%, and in the general population (prevalence, 1 in
      250) it was about 1%. The negative PVs for both CAP and UNICAP were close to
      100%; thus, when the AGA test was negative, the risk for CD was small.
      Interestingly, five children had serum IgA levels below the detection limit
      (<0.07 g/liter) when on a gluten-free diet, whereas they had normal levels at the
      time of the first biopsy. In conclusion, the automated immunoassays--based on
      ImmunoCAP technology--for analysis of IgA-AGA had a reliability comparable to
      that of the in-house methods.

PMID- 11329460
TI  - Use of synthetic peptides derived from the antigens ESAT-6 and CFP-10 for
      differential diagnosis of bovine tuberculosis in cattle.
AB  - In Great Britain an independent scientific review for the government has
      concluded that the development of a cattle vaccine against Mycobacterium bovis
      infection holds the best long-term prospect for tuberculosis control in British
      herds. A precondition for vaccination is the development of a complementary
      diagnostic test to differentiate between vaccinated animals and those infected
      with M. bovis so that testing and slaughter-based control strategies can continue
      alongside vaccination. To date bacillus Calmette-Guerin (BCG), an attenuated
      strain of M. bovis, is the only available vaccine for the prevention of
      tuberculosis. However, tests based on tuberculin purified protein derivative
      cannot distinguish between M. bovis infection and BCG vaccination. Therefore,
      specific antigens expressed by M. bovis but absent from BCG constitute prime
      candidates for differential diagnostic reagents. Recently, two such antigens,
      ESAT-6 and CFP-10, have been reported to be promising candidates as diagnostic
      reagents for the detection of M. bovis infection in cattle. Here we report the
      identification of promiscuous peptides of CFP-10 that were recognized by M. bovis
      infected cattle. Five of these peptides were formulated into a peptide cocktail
      together with five peptides derived from ESAT-6. Using this peptide cocktail in T
      cell assays, M. bovis-infected animals were detected, while BCG-vaccinated or
      Mycobacterium avium-sensitized animals did not respond. The sensitivity of the
      peptide cocktail as an antigen in a whole-blood gamma interferon assay was
      determined using naturally infected field reactor cattle, and the specificity was
      determined using blood from BCG-vaccinated and noninfected, nonvaccinated
      animals. The sensitivity of the assay in cattle with confirmed tuberculosis was
      found to be 77.9%, with a specificity of 100% in BCG-vaccinated or nonvaccinated
      animals. This compares favorably with the specificity of tuberculin when tested
      in noninfected or vaccinated animals. In summary, our results demonstrate that
      this peptide cocktail can discriminate between M. bovis infection and BCG
      vaccination with a high degree of sensitivity and specificity.

PMID- 11329461
TI  - Immunoblot profile as predictor of toxoplasmic encephalitis in patients infected
      with human immunodeficiency virus.
AB  - In order to define more accurately human immunodeficiency virus-infected patients
      at risk of developing toxoplasmic encephalitis (TE), we assessed the prognostic
      significance of the anti-Toxoplasma gondii immunoglobulin G (IgG) immunoblot
      profile, in addition to AIDS stage, a CD4(+) cell count <50/mm(3), and an
      antibody titer > or =150 IU/ml, in patients with CD4 cell counts <200/mm(3) and
      seropositive for T. gondii. Baseline serum samples from 152 patients included in
      the placebo arm of the ANRS 005-ACTG 154 trial (pyrimethamine versus placebo)
      were used. The IgG immunoblot profile was determined using a Toxoplasma lysate
      and read using the Kodak Digital Science 1D image analysis software. Mean follow
      up was 15.1 months, and the 1-year incidence of TE was 15.9%. The cumulative
      probability of TE varied according to the type and number of anti-T. gondii IgG
      bands and reached 65% at 12 months for patients with IgG bands of 25 and 22 kDa.
      In a Cox model adjusted for age, gender, Centers for Disease Control and
      Prevention (CDC) clinical stage, and CD4 and CD8 cell counts, the incidence of TE
      was higher when the IgG 22-kDa band (hazard ratio [HR] = 5.4; P < 0.001), the IgG
      25-kDa band (HR = 4.7; P < 0.001), or the IgG 69-kDa band (HR = 3.4; P < 0.001)
      was present and was higher for patients at CDC stage C (HR = 4.9; P < 0.001). T.
      gondii antibody titer and CD4 cell count were not predictive of TE. Thus,
      detection of IgG bands of 25, 22, and/or 69 kDa may be helpful for deciding when
      primary prophylaxis for TE should be started or discontinued, especially in the
      era of highly active antiretroviral therapy.

PMID- 11329462
TI  - New assay for measuring cell surface hydrophobicities of Candida dubliniensis and
      Candida albicans.
AB  - Hydrophobic interactions, based on cell surface hydrophobicity (CSH), are among
      the many and varied mechanisms of adherence deployed by the pathogenic yeast
      Candida albicans. Recently it was shown that, unlike C. albicans, C. dubliniensis
      is a species that exhibits an outer fibrillar layer consistent with constant CSH.
      Previously, C. dubliniensis grown at 25 or 37 degrees C was shown to coaggregate
      with the oral anaerobic bacterium Fusobacterium nucleatum. C. albicans, however,
      demonstrated similar coaggregation only when hydrophobic or grown at 25 degrees
      C. This observation implied that coaggregation of Candida cells with F. nucleatum
      is associated with a hydrophobic yeast cell surface. To test this hypothesis, 42
      C. albicans and 40 C. dubliniensis clinical isolates, including a C. albicans
      hydrophobic variant, were grown at 25 and 37 degrees C and tested with the
      established hydrophobicity microsphere assay, which determines CSH levels based
      on the number of microspheres attached to the yeast cells. The coaggregation
      assay was performed in parallel experiments. All C. dubliniensis isolates grown
      at either temperature, hydrophobic 25 degrees C-grown C. albicans isolates, and
      the C. albicans hydrophobic variant, unlike the 37 degrees C-hydrophilic C.
      albicans isolates, exhibited hydrophobic CSH levels with the microsphere assay
      and simultaneously showed maximum, 4+, coaggregation with F. nucleatum. The
      parallel results obtained for C. dubliniensis using both assays support the use
      of the CoAg assay both as a rapid assay to determine CSH and to differentiate
      between C. dubliniensis and C. albicans.

PMID- 11329463
TI  - Comparison of two commercial microimmunofluorescence kits and an enzyme
      immunoassay kit for detection of serum immunoglobulin G antibodies to Chlamydia
      pneumoniae.
AB  - We compared the MRL and the Labsystems Chlamydia pneumoniae
      microimmunofluorescence (MIF) immunoglobulin G (IgG) kits and the Labsystems
      enzyme immunoassay (EIA) kit in a blinded study of 83 serum samples in which we
      evaluated titers, cross-reactivity to other species, and reproducibility. There
      was no statistically significant difference between the MRL and the Labsystems
      MIF kits in the endpoint titers of IgG antibody to C. pneumoniae. The correlation
      between the results obtained with these two MIF kits was excellent (r = 0.95; P =
      0.001). The cross-reactivity of the C. pneumoniae-positive sera with C.
      trachomatis- and C. psittaci-positive sera was assessed for each MIF kit. For C.
      pneumoniae-positive sera with titers of > or =32, the Labsystems MIF kit
      exhibited more cross-reactivity to C. psittaci than the MRL kit did. The values
      obtained with the Labsystems EIA kit represented single dilutions of serum
      specimens expressed as enzymeimmuno units on a continuous scale. The results
      obtained with the Labsystems EIA kit correlated moderately well with those
      obtained with each MIF kit when they were compared for their abilities to detect
      IgG antibodies to C. pneumoniae (for the MRL MIF kit, r = 0.79 [P = 0.001]; for
      the Labsystems MIF kit, r = 0.78 [P = 0.001]). The results obtained with the
      commercial MRL and Labsystems MIF kits and the Labsystems EIA kit tested were
      reproducible; and the kits were standardized, had quality control reagents, and
      are suitable for detection of C. pneumoniae antibodies in serum and for use in
      interlaboratory studies. Validation of the use of these kits for clinical
      diagnosis still needs further evaluation.

PMID- 11329464
TI  - Effect of intranasal administration of Lactobacillus casei Shirota on influenza
      virus infection of upper respiratory tract in mice.
AB  - In mice administered Lactobacillus casei strain Shirota (LcS) intranasally,
      potent induction of interleukin 12, gamma interferon, and tumor necrosis factor
      alpha, which play a very important role in excluding influenza virus (IFV), was
      evident in mediastinal lymph node cells. In this model of upper respiratory IFV
      infection, the titers of virus in the nasal wash of mice inoculated with 200
      microg of LcS for three consecutive days (LcS 200 group) before infection were
      significantly (P < 0.01) lower than those of mice not inoculated with LcS
      (control group) (10(0.9 +/- 0.6) versus 10(2.1 +/- 1.0)). The IFV titer was
      decreased to about 1/10 of the control level. Using this infection model with
      modifications, we investigated whether the survival rate of mice was increased by
      intranasal administration of LcS. The survival rate of the mice in the LcS 200
      group was significantly (P < 0.05) greater than that of the mice in the control
      group (69% versus 15%). It seems that the decrease in the titer of virus in the
      upper respiratory tract to 1/10 of the control level was important in preventing
      death. These findings suggest that intranasal administration of LcS enhances
      cellular immunity in the respiratory tract and protects against influenza virus
      infection.

PMID- 11329465
TI  - Antigenic importance of the carboxy-terminal beta-strand of the porcine
      reproductive and respiratory syndrome virus nucleocapsid protein.
AB  - Five domains of antigenic importance were previously mapped on the nucleocapsid
      protein (N) of the porcine reproductive and respiratory syndrome virus (PRRSV),
      and a domain comprised of the 11 C-terminal-most amino acids (residues 112 to
      123) was shown to be essential for binding of N-specific conformation-dependent
      monoclonal antibodies (MAbs). In the present study, the importance of individual
      residues within this C-terminal domain for antigenicity was investigated using
      eight different mutant constructs of N expressed in HeLa cells. Single amino acid
      substitutions were introduced into the C-terminal domain of the N protein, and
      the significance of individual amino acids for MAb reactivity was determined by
      immunoprecipitation. None of the MAbs tested recognized the mutant with a leucine
      to-proline substitution at residue 114 (L114P), while V112P, R113P, R113D, I115P,
      and R116P reduced MAb binding significantly. Conversely, substitution of amino
      acids at positions 118 (T118S) and 121 (P121A) had little effect on MAb binding.
      Secondary-structure predictions indicate that amino acids 111 to 117 form a beta
      strand. In view of the fact that replacement of beta-strand-forming amino acids
      with proline elicited the greatest effect on MAb binding, it appears that
      secondary structure in the C terminus of the N protein is an important
      determinant of conformational epitope formation. While the crystal structure of
      the PRRSV N protein remains to be determined, results from these studies broaden
      our understanding of the secondary structures that make up the PRRSV N protein
      and shed some light on how they may relate to function.

PMID- 11329466
TI  - Presence of human T-cell responses to the Mycobacterium leprae 45-kilodalton
      antigen reflects infection with or exposure to M. leprae.
AB  - The ability of the 45-kDa serine-rich Mycobacterium leprae antigen to stimulate
      peripheral blood mononuclear cell (PBMC) proliferation and gamma interferon (IFN
      gamma) production was measured in leprosy patients, household contacts, and
      healthy controls from areas of endemicity in Mexico. Almost all the tuberculoid
      leprosy patients gave strong PBMC proliferation responses to the M. leprae 45-kDa
      antigen (92.8%; n = 14). Responses were lower in lepromatous leprosy patients
      (60.6%; n = 34), but some responses to the 45-kDa antigen were detected in
      patients unresponsive to M. leprae sonicate. The proportion of positive responses
      to the M. leprae 45-kDa antigen was much higher in leprosy contacts (88%; n = 17)
      than in controls from areas of endemicity (10%; n = 20). None of 15 patients with
      pulmonary tuberculosis gave a positive proliferation response to the 45-kDa
      antigen. The 45-kDa antigen induced IFN-gamma secretion similar to that induced
      by the native Mycobacterium tuberculosis 30/31-kDa antigen in tuberculoid leprosy
      patients and higher responses than those induced by the other recombinant
      antigens (M. leprae 10- and 65-kDa antigens, thioredoxin, and thioredoxin
      reductase); in patients with pulmonary tuberculosis it induced lower IFN-gamma
      secretion than the other recombinant antigens. These results suggest that the M.
      leprae 45-kDa antigen is a potent T-cell antigen which is M. leprae specific in
      these Mexican donors. This antigen may therefore have diagnostic potential as a
      new skin test reagent or as an antigen in a simple whole-blood cytokine test.

PMID- 11329467
TI  - Canine parvovirus (CPV) vaccination: comparison of neutralizing antibody
      responses in pups after inoculation with CPV2 or CPV2b modified live virus
      vaccine.
AB  - Canine parvovirus type 2 (CPV2) emerged in 1978 as causative agent of a new
      disease of dogs. New antigenic variants (biotypes), designated CPV2a and CPV2b,
      became widespread during 1979 to 1980 and 1984, respectively. At the present time
      the original CPV2 has disappeared in the dog population and has been replaced by
      the two new viruses. In the present study the comparison of neutralizing antibody
      titers in two groups of pups (18 pups in each group) inoculated with CPV2 and
      CPV2b modified live virus vaccines is reported. Using the hemagglutination
      inhibition (HI) test, relevant differences between antibody titers, against
      either the homologous or the heterologous virus, were not constantly observed.
      Using the neutralization (Nt) test, however, the pups inoculated with CPV2 had
      antibody titers which were approximately 30 times higher to the homologous virus
      (mean, 4,732) than to the heterologous virus (CPV2b) (mean, 162). The results of
      these experiments support two conclusions: (i) the HI test may not always
      accurately evaluate the true immune status of dogs with respect to CPV, and (ii)
      dogs inoculated with CPV2 vaccine develop relatively low Nt antibody titers
      against the heterologous virus (CPV2b). These data may suggest an advantage for
      new vaccines, considering that most presently licensed vaccines are produced with
      CPV2, which no longer exists in the dog population.

PMID- 11329468
TI  - Importance of complement source in measuring meningococcal bactericidal titers.
AB  - Complement-mediated bactericidal antibodies in serum confer protection against
      meningococcal disease. The minimum protective titer is estimated to be between
      1:4 and 1:8 when measured by the Goldschneider assay performed with human
      complement, the assay used in the 1960s to establish the correlation between
      bactericidal antibodies and protection. A more recently described bactericidal
      assay standardized by an international consortium uses rabbit complement, which
      is known to augment bactericidal titers. To define a protective titer measured by
      the standardized assay, we compared bactericidal titers against serogroup C
      strains measured by this assay to titers measured by the assay described by
      Goldschneider et al. A titer of > or =1:128 measured by the standardized assay
      was needed to predict with > or =80% certainty a positive titer of > or =1:4 as
      measured by the Goldschneider assay. However, the majority of samples with titers
      of 1:4 measured by the Goldschneider assay had titers of <1:128 when measured by
      the standardized assay. Therefore, by the results of the standardized assay such
      persons would be falsely categorized as being susceptible to disease. In
      conclusion, high bactericidal titers measured with the standardized assay
      performed with rabbit complement are predictive of protection, but no threshold
      titer is both sensitive and specific for predicting a positive titer measured by
      the Goldschneider assay using human complement. Up to 10% of the U.S. adult
      population lacks intrinsic bactericidal activity against serogroup C strains in
      serum and can serve as complement donors. Therefore, use of the Goldschneider
      assay or an equivalent assay performed with human complement is preferred over
      assays that use rabbit complement.

PMID- 11329469
TI  - Distribution of antibody against Erysipelothrix rhusiopathiae in cattle.
AB  - Serum samples collected from 854 cattle in nine prefectures of Japan, from
      Hokkaido to Okinawa, between 1988 and 1992 were examined for presence of
      antibodies against Erysipelothrix rhusiopathiae by growth agglutination test.
      Most of the sera showed positive reactions, and the antibody titers ranged from
      below 4 to above 128. Seventy-six percent of the sera showed titers of 32 or
      above, and 34% showed titers of 128 or above. The titers had a tendency to be
      higher in the south and lower in the north and were clearly low in sera from
      areas with no swine industry. These results indicated that Japanese cattle had
      been infected with E. rhusiopathiae and that clinical cases of the disease were
      possible.

PMID- 11329470
TI  - Gamma interferon expression in CD8(+) T cells is a marker for circulating
      cytotoxic T lymphocytes that recognize an HLA A2-restricted epitope of human
      cytomegalovirus phosphoprotein pp65.
AB  - Antigen-specific CD8(+) T cells with cytotoxic activity are often critical in
      immune responses to infectious pathogens. To determine whether gamma interferon
      (IFN-gamma) expression is a surrogate marker for cytotoxic T lymphocytes (CTL),
      human cytomegalovirus-specific CTL responses were correlated with CD8(+) T-cell
      IFN-gamma expression determined by cytokine flow cytometry. A strong positive
      correlation was observed between specific lysis of peptide-pulsed targets in a
      (51)Cr release assay and frequencies of peptide-activated CD8(+) T cells
      expressing IFN-gamma at 6 h (r(2) = 0.72) or 7 days (r(2) = 0.91). Enumeration of
      responding cells expressing perforin, another marker associated with CTL, did not
      improve this correlation. These results demonstrate that IFN-gamma expression can
      be a functional surrogate for identification of CTL precursor cells.

PMID- 11329472
TI  - Prevalence of known P-fimbrial G alleles in Escherichia coli and identification
      of a new adhesin class.
AB  - Screening a large Escherichia coli collection for P-fimbrial adhesin classes
      identified 20 unclassifiable strains. Cloning and sequencing of papG from an
      unclassifiable strain identified another G allele. The novel adhesin gene has 65%
      identity to the class I adhesin gene, 44% identity to the class II adhesin gene,
      and 43% identity to the class III adhesin gene.

PMID- 11329471
TI  - Elastase deficiency phenotype of Pseudomonas aeruginosa canine otitis externa
      isolates.
AB  - Pseudomonas aeruginosa veterinary isolates were assayed for elastase and total
      matrix protease activity. The elastase activity of canine ear isolates was much
      less than that of strain PAO1 and that of all other veterinary isolates (P <
      0.0001). The results indicate that canine ear isolates have a distinct elastase
      phenotype.

PMID- 11329473
TI  - Seroprevalence of canine distemper virus in cats.
AB  - A seroepidemiological survey of canine distemper virus (CDV) infection in Asian
      felids revealed that the prevalence of antibodies varied depending on region and,
      in some cases, exposure to dogs. The serologic pattern in cats with antibodies
      indicated that they had likely been exposed to field strains rather than typical
      CDV vaccine strains.

PMID- 11329474
TI  - Detection of antibodies to Babesia equi in horses by a latex agglutination test
      using recombinant EMA-1.
AB  - A latex agglutination test (LAT) using recombinant equi merozoite antigen 1 (EMA
      1) for the detection of antibodies to Babesia equi was developed. The LAT was
      able to differentiate very clearly between sera from B. equi-infected horses and
      sera from Babesia caballi-infected horses or from normal horses. The LAT results
      were identical to those of a previously developed enzyme-linked immunosorbent
      assay. These results indicate that LAT using recombinant EMA-1 might be very
      useful as a routine screening method for the diagnosis of B. equi infection.

PMID- 11329475
TI  - Characterization of a monoclonal antibody that binds to an epitope on soluble
      bacterial peptidoglycan fragments.
AB  - We employed an inhibition-type enzyme-linked immunosorbent assay (ELISA) to
      characterize a murine immunoglobulin M monoclonal antibody (MAb) that bound
      soluble macromolecular peptidoglycan (PG). With this ELISA, the MAb was capable
      of detecting soluble PG concentrations of less than 10 ng/ml. Enzymatic digestion
      of PG reduced binding by more than 100-fold, implying that the epitope recognized
      by this antibody depended on repeating subunits within the glycan backbone.
      Additionally, the MAb bound to epitopes on both O-acetylated and non-O-acetylated
      PG fragments from gram-negative bacteria, as well as PG fragments from
      Staphylococcus aureus and PG fragments released into the medium by a number of
      gram-positive and gram-negative bacteria.

PMID- 11329476
TI  - Oral administration of influenza vaccine in combination with the adjuvants LT-K63
      and LT-R72 induces potent immune responses comparable to or stronger than
      traditional intramuscular immunization.
AB  - Mucosal immunization strategies are actively being pursued in the hopes of
      improving the efficacy of vaccines against the influenza virus. Our group
      investigated the oral immunization of mice via intragastric gavage with influenza
      hemagglutinin (HA) combined with mutant Escherichia coli heat-labile enterotoxins
      K63 (LT-K63) and R72 (LT-R72). These oral immunizations resulted in potent serum
      antibody and HA inhibition titers, in some cases stronger than those obtained
      with traditional intramuscular administration, in addition to HA-specific
      immunoglobulin A in the saliva and nasal secretions. This study demonstrates that
      it may be possible to develop effective oral influenza vaccines.

PMID- 11329477
TI  - Detection of immunologically significant factors for chronic fatigue syndrome
      using neural-network classifiers.
AB  - Neural-network classifiers were used to detect immunological differences in
      groups of chronic fatigue syndrome (CFS) patients that heretofore had not shown
      significant differences from controls. In the past linear methods were unable to
      detect differences between CFS groups and non-CFS control groups in the
      nonveteran population. An examination of the cluster structure for 29
      immunological factors revealed a complex, nonlinear decision surface. Multilayer
      neural networks showed an over 16% improvement in an n-fold resampling
      generalization test on unseen data. A sensitivity analysis of the network found
      differences between groups that are consistent with the hypothesis that CFS
      symptoms are a consequence of immune system dysregulation. Corresponding
      decreases in the CD19(+) B-cell compartment and the CD34(+) hematopoietic
      progenitor subpopulation were also detected by the neural network, consistent
      with the T-cell expansion. Of significant interest was the fact that, of all the
      cytokines evaluated, the only one to be in the final model was interleukin-4 (IL
      4). Seeing an increase in IL-4 suggests a shift to a type 2 cytokine pattern.
      Such a shift has been hypothesized, but until now convincing evidence to support
      that hypothesis has been lacking.

PMID- 11329478
TI  - Pathogenic potential of canine parvovirus types 2a and 2c in domestic cats.
AB  - The in vivo pathogenicity of canine parvovirus (CPV) type 2c (strain V203) and of
      CPV type 2a (strain V154) against cats was investigated. Our results indicate
      that both types of CPV have the potential to induce disease in cats.

PMID- 11329479
TI  - Managed mental health care: attitudes and ethical beliefs of child and pediatric
      psychologists.
AB  - OBJECTIVE: To examine child and pediatric psychologists' ethical beliefs and
      attitudes toward managed mental health care. METHODS: In a survey mailed in
      spring 1997, 252 child and pediatric psychologists responded to three vignettes
      depicting ethical dilemmas related to working with managed mental health care
      (confidentiality, restriction of services, misdiagnosis). Data were collected
      about psychologists' ethical choices and reasons given for choices, attitudes
      toward managed care, the extent to which managed care affected ethical decision
      making, and level of managed care involvement. RESULTS: Differences were found in
      choices made for the ethical dilemmas in regard to what participants thought they
      should do, would do, and actually did do. Overall, participants endorsed negative
      attitudes toward managed care. Participants reported that managed care somewhat
      affected their ethical decision making for the vignettes. Level of managed care
      involvement was not related to ethical decision making or attitudes toward
      managed care. CONCLUSIONS: The findings suggest areas for examination as new
      ethical standards are created for work in managed care environments.

PMID- 11329480
TI  - Multidimensional assessment of pain in pediatric sickle cell disease.
AB  - OBJECTIVE: To conduct a multidimensional assessment of pain in children with
      sickle cell disease (SCD). Variables included parent and child reports of pain
      location and intensity, qualitative descriptors of pain, perceptions regarding
      the seriousness and severity of SCD, and environmental and emotional factors
      associated with pain. METHODS: We replicated previous SCD pain research and
      applied advanced assessment methodology and research design to a population of
      pediatric SCD patients and their caregivers. RESULTS: Convergence of data
      supports the utility of multidimensional pain assessment with parents and
      children with SCD. SCD pain is experienced as intense and severe in home and
      hospital environments. CONCLUSIONS: Findings support including children as
      reporters in clinical assessment of SCD pain. Integration of assessment
      strategies into home-based pain management may improve health outcomes. Future
      research should target biobehavioral treatment for pediatric SCD pain.

PMID- 11329481
TI  - Observational assessment of family functioning at mealtime in preschool children
      with cystic fibrosis.
AB  - OBJECTIVE: To examine functioning during a dinner meal in families of a child
      with a chronic illness that requires dietary treatment recommendations, as
      compared to families of a child without a chronic illness. METHODS: Ratings of
      seven dimensions of family functioning on the McMaster Mealtime Family
      Interaction Coding System (MICS) were obtained on 29 families of children with CF
      and 29 families of children with no chronic illness, ages 2 to 6 years, during a
      videotaped dinner meal at home. RESULTS: Ratings of families with a child with CF
      were significantly lower than those for families of children without a chronic
      illness on Overall Family Functioning and five of the six MICS dimensions:
      Communication, Interpersonal Involvement, Affect Management, Behavior Control,
      and Role Allocation and approached significance on the Task Accomplishment
      dimension. The ratings of families of a child with CF were in the "clinically
      significant" range on all subcales, including Task ACCOMPLISHMENT. CONCLUSIONS:
      This study suggests that family functioning at mealtimes may be different in
      families of children with CF in which explicit dietary guidelines exist than in
      families of children with no illness or dietary guidelines. These results are
      discussed in terms of global family functioning and treatment approaches to
      dietary treatment recommendations.

PMID- 11329482
TI  - Psychological adaptation and social support of parents of pediatric cancer
      patients: a prospective longitudinal study.
AB  - OBJECTIVE: To investigate levels of support and the concurrent and prospective
      effects of support on the psychological functioning of parents of children with
      cancer in a prospective longitudinal study. METHODS: Parents' (n = 128) self
      perceived level of psychological distress, quantity of support, and
      dissatisfaction with support were assessed, at diagnosis, at 6, and at 12 months.
      RESULTS: Parents received most support at diagnosis. Self-perceived quantity
      decreased with time, but parents indicated they remained equally satisfied.
      Support significantly predicted concurrent and prospective distress of fathers,
      but not of mothers. Dissatisfaction with support and negative interactions were
      consistent risk factors for fathers. Mothers who adjusted well psychologically
      received more support and were less dissatisfied than mothers who remained
      clinically distressed. Nevertheless, no persisting effect of support was found.
      CONCLUSIONS: Findings illustrate that social support varies with the stress
      situation and with gender. Identification of vulnerable parents at diagnosis on
      the basis of their perception of received quantity of and dissatisfaction with
      support seems difficult. Intervention efforts aimed at mobilization of needed
      support may be efficacious.

PMID- 11329483
TI  - Risk and resistance factors in the adaptation in mothers of children with
      juvenile rheumatoid arthritis.
AB  - OBJECTIVE: To examine the importance of illness severity, child functional
      status, psychosocial stress, intrapersonal factors, stress processing, and social
      ecological factors in predicting psychological symptoms among mothers of children
      with juvenile rheumatoid arthritis (JRA). METHODS: Mothers of 92 children with
      JRA completed surveys while waiting with their children for physician
      appointments or during JRA meeting breaks. RESULTS: Mothers reported higher mean
      levels of psychological symptoms than a normative group. Higher levels of
      psychosocial stress predicted increased psychological symptoms after accounting
      for disease severity and functional status. Maternal appraisal of the illness
      tended to moderate the relationship between illness stress and psychological
      symptoms, and maternal education moderated the relationship between daily hassles
      stress and psychological symptoms. CONCLUSIONS: These data indicate that mothers
      of children with JRA are at risk for psychological distress. Inteventions that
      take into account the buffering effects of maternal education and appraisal may
      serve to decrease the effects of maternal stress.

PMID- 11329484
TI  - Brief report: perceptions of young adolescents about a hypothetical new peer with
      cancer: an analog study.
AB  - OBJECTIVE: To assess attitudes and behavioral intentions (desire to engage a peer
      in academic, social, and general activities) of young adolescents toward a
      hypothetical new peer with cancer and to assess the relationship between
      attitudes and empathy. METHODS: Two hundred fifty middle school students viewed
      videotapes of a hypothetical peer (i.e., actor) with or without cancer.
      Participants completed a measure of empathy and a measure of social desirability
      before viewing the videotape. Participants completed a measure of attitudes and a
      measure of behavioral intentions after viewing the videotape. RESULTS:
      Participants gave significantly higher ratings of behavioral intention (e.g.,
      were more accepting) to the peer with cancer than to the healthy peer. Also,
      participants with high empathy reported more favorable impressions toward the
      hypothetical new peer than did participants with low or moderate empathy. Female
      participants had more favorable attitudes and behavioral intentions toward the
      hypothetical new peer than did male participants. CONCLUSIONS: The social
      perceptions of young adolescents about peers with cancer may be less negative
      than previously hypothesized.

PMID- 11329485
TI  - The living legacy of science: in memory of Markku Linnoila, MD, PhD.

PMID- 11329486
TI  - Serotonergic dysfunction, negative mood states, and response to alcohol.
AB  - BACKGROUND: Dysfunction of central serotonergic neurotransmission has been
      implicated in the pathogenesis and maintenance of alcoholism. Serotonergic
      dysfunction may be associated with three behavior patterns relevant for
      alcoholism: impulsive aggression, negative mood states, and a low response to
      alcohol intake. METHODS: We reviewed the literature on the psychopathological
      correlates of serotonergic dysfunction and focused on studies that assess the
      interaction between negative mood states and alcohol response. RESULTS:
      Prospective studies in nonhuman primates that underwent early separation stress
      found an association between a low serotonin turnover rate and the disposition to
      excessive alcohol intake and impulsive aggression. These findings seem to be
      relevant for a subgroup of alcoholics with a low serotonin turnover rate and
      antisocial personality traits. Cross-sectional data in humans also support a
      relationship between reduced serotonergic neurotransmission and aggressive
      behavior and indicate that the association of serotonergic dysfunction and
      aggression may be mediated by negative mood states. This hypothesis is in
      accordance with a large body of data linking anxiety and depression to
      serotonergic dysfunction. In human alcoholics, brain imaging has detected a
      reduction in serotonin transporter availability in association with depression.
      Serotonin transporter availability seems to be related to reduced GABA-ergic
      sedation and the acute response to alcohol intake, an important predictor of
      subsequent development of alcohol dependence. CONCLUSIONS: Several lines of
      evidence point to a relationship between serotonergic dysfunction, negative mood
      states, and excessive alcohol intake, which may be mediated in part by reduced
      alcohol-induced sedation.

PMID- 11329487
TI  - Ethanol decreases expression of p21 and increases hyperphosphorylated pRb in cell
      lines of squamous cell carcinomas of the head and neck.
AB  - BACKGROUND: Alcohol increases the risk of cancers of the upper aerodigestive
      tract, but the biological mechanisms of this ethanol effect are still unclear. We
      recently reported that ethanol is able to induce in vitro proliferation
      accompanied by an increased number of cells in the S phase of the cell cycle in
      squamous cell carcinoma cell lines of the head and neck (SCCHN). In the current
      study we investigated the influence of ethanol over a limited period of time (96
      hr) on cell cycle-regulating proteins involved in G1/S phase transition. METHODS:
      Synchronized cells of SCCHN cell lines JPPA (larynx) and SCC 9 and SCC 25
      (tongue), as well as HaCaT (human immortalized keratinocytes)-used as a control
      were cultured for 96 hr in the presence or absence of ethanol (10-3M). At several
      time intervals the expression of cyclin D1 and p21 and the phosphorylation status
      of the retinoblastoma protein (pRb) were determined by Western or Northern Blot
      analysis, or both. RESULTS: Ethanol had no influence on the protein expression of
      cyclin D1. In contrast, a distinct downregulation of p21 at the protein as well
      as the mRNA level could be detected. Furthermore, as a downstream event, the
      hyperphosphorylated form of the pRb increased. CONCLUSIONS: In the acute alcohol
      in vitro experiments, the marked downregulation of the important cell cycle
      inhibitor p21 and the corresponding increase of hyperphosphorylated pRb
      accelerate the progression of cells from the G1 to the S phase in the cell cycle.
      The importance of these data and their relevance to in vivo conditions remain
      speculative, but it could be a critical step in the multistep process of SCCHN
      carcinogenesis induced by ethanol.

PMID- 11329488
TI  - Gender differences in pharmacokinetics of alcohol.
AB  - BACKGROUND: The enhanced vulnerability of women to develop alcohol-related
      diseases may be due to their higher blood alcohol levels after drinking, but the
      mechanism for this effect is debated. METHODS: Sixty-five healthy volunteers of
      both genders drank 0.3 g of ethanol/kg of body weight (as 5%, 10%, or 40%
      solutions) postprandially. Blood alcohol concentrations were monitored by breath
      analysis and compared with those after intravenous infusion of the same dose.
      First-pass metabolism was quantified (using Michaelis-Menten kinetics) as the
      route-dependent difference in the amount of ethanol reaching the systemic blood.
      Gastric emptying was assessed by nuclear scanning after intake of 300 microCurie
      of technetium-labeled diethylene triamine pentacetic acid in 10% ethanol. The
      activities of alcohol dehydrogenase isozymes were assessed in 58 gastric
      biopsies, using preferred substrates for gamma-ADH (acetaldehyde) and for final
      sigma-ADH (m-nitrobenzaldehyde) and a specific reaction of chi-ADH (glutathione
      dependent formaldehyde dehydrogenase). RESULTS: Women had less first-pass
      metabolism than men when given 10% or 40%, but not 5%, alcohol. This was
      associated with lower gastric chi-ADH activity; its low affinity for ethanol
      could explain the greater gender difference in first-pass metabolism with high
      rather than with low concentrations of imbibed alcohol. Alcohol gastric emptying
      was 42% slower and hepatic oxidation was 10% higher in women. A 7.3% smaller
      volume of alcohol distribution contributed to the higher ethanol levels in women,
      but it did not account for the route-dependent effects. CONCLUSIONS: The gender
      difference in alcohol levels is due mainly to a smaller gastric metabolism in
      females (because of a significantly lesser activity of chi-ADH), rather than to
      differences in gastric emptying or in hepatic oxidation of ethanol. The
      concentration-dependency of these effects may explain earlier discrepancies. The
      combined pharmacokinetic differences may increase the vulnerability of women to
      the effects of ethanol.

PMID- 11329489
TI  - Influence of age, sex, and Helicobacter pylori infection before and after
      eradication on gastric alcohol dehydrogenase activity.
AB  - BACKGROUND: Gastric alcohol dehydrogenase may contribute to the metabolism of
      orally ingested ethanol and decrease the bioavailability of the drug. The aims of
      this study were to assess the impact of Helicobacter pylori infection and its
      eradication on gastric alcohol dehydrogenase activity and to relate the findings
      to gastric histology. Furthermore, the role of age- and sex-related differences
      in gastric alcohol dehydrogenase activity were studied. METHODS: A total of 76
      subjects (39 women and 37 men) underwent upper gastrointestinal endoscopy, and
      biopsies were obtained from the corpus and antrum. The specimens were used for
      determining gastric alcohol dehydrogenase activity, histological examination, and
      urease testing. Subjects with H. pylori infection (n = 36) received medication to
      eradicate the infection, and repeat biopsies were taken 2 and 12 months later.
      RESULTS: No significant difference in gastric alcohol dehydrogenase activity was
      found between men and women (p > 0.05). Gastric alcohol dehydrogenase activity
      did not differ significantly between the subjects older than 50 years (n = 39)
      and those 50 years or younger (n = 37). In subjects with H. pylori infection,
      gastric alcohol dehydrogenase activity was significantly reduced in the antrum (p
      < 0.05). After eradication of H. pylori, alcohol dehydrogenase activity in the
      antrum increased significantly within 2 months (p < 0.01). Antral biopsies with
      the most pronounced inflammation and histological changes had significantly
      decreased alcohol dehydrogenase activity (p < 0.05). In contrast, no significant
      differences were found in corpus. CONCLUSIONS: H. pylori infection is associated
      with decreased antral alcohol dehydrogenase activity, which seems to be related
      to the severity of the inflammatory changes in the mucosa. Eradication of H.
      pylori normalizes antral alcohol dehydrogenase activity within 2 months.

PMID- 11329490
TI  - Effect of 4-methylpyrazole on endogenous plasma ethanol and methanol levels in
      humans.
AB  - BACKGROUND: Endogenous methanol and ethanol levels are found in human blood. It
      is assumed that these compounds are derived mainly from microflora in the
      gastrointestinal tract and that the small amounts formed are consequently
      eliminated, mainly in the liver, by the alcohol dehydrogenase (ADH) pathway. The
      objective of the present study was to investigate the effect of 4-methylpyrazole
      (4-MP), a specific ADH inhibitor, on endogenous plasma methanol and ethanol
      levels in healthy women and men. METHODS: A double-blind placebo-controlled
      interventional study was carried out. RESULTS: A significant elevation in plasma
      endogenous ethanol and methanol levels was observed after intake of 4-MP (10-15
      mg/kg p.o.). For methanol levels, a linear increase from 20 +/- 14 micromol/l
      before intake to 39 +/- 22 micromol/l at 420 min from intake of 4-MP (levels 20
      +/- 14 micromol/l and 14 +/- 9 micromol/l during the corresponding placebo time
      points) was found. For ethanol, concentrations increased from levels below
      detection limit (i.e., < 5 micromol/l, determined by headspace gas
      chromatography) before intake to 30 +/- 20 micromol/l at 195 min from intake of 4
      MP. A small increase in ethanol levels, to 13 +/- 8 micromol/l, but not in
      methanol levels, was observed after the intake of lingonberry juice containing no
      ethanol or methanol. No sex differences in the ethanol and methanol levels before
      or after the intake of 4-MP were found. CONCLUSIONS: The present study provides
      conclusive evidence for a constant endogenous production as well as clearance of
      ethanol and methanol in humans. In addition, the study shows that the ethanol and
      methanol produced are, at least in part, eliminated by the ADH pathway.

PMID- 11329491
TI  - Local cerebral glucose utilization rates in alcohol-naive high-alcohol-drinking
      (HAD) and low-alcohol-drinking (LAD) rats.
AB  - BACKGROUND: The present study compared baseline local cerebral glucose
      utilization (LCGU) values within reward-relevant brain regions in alcohol-naive,
      adult male high-alcohol-drinking (HAD) and low-alcohol-drinking (LAD) rats from
      replicate lines 1 and 2. METHODS: 2-[14C]Deoxyglucose ([14C]2-DG) was injected
      (125 microCi/kg) intravenously during the rats' dark cycle. Timed arterial blood
      samples were collected over 45 min and assayed for glucose as well as [14C]2-DG
      content. Rats were then decapitated; their brains quickly removed and frozen in
      isopentane at -50 degrees C. Coronal sections from each brain were apposed to
      film and exposed for 2 days. Image densities were analyzed using quantitative
      autoradiography. RESULTS: Data were collected from several key limbic (nucleus
      accumbens, ventral tegmental area, olfactory tubercle, amygdala, hippocampus,
      ventral pallidum, and septum), basal ganglia, cortical (medial prefrontal,
      frontal, parietal, temporal, occipital, entorhinal, pyriform, and cingulate), and
      subcortical (thalamus, habenula, and superior colliculus) structures. Because
      there were no significant differences between the replicates within each drinking
      line, data from the two replicates were combined to determine drinking line
      differences. When both replicate lines were combined, there were trends toward
      higher (approximately 15%) LCGU rates in HAD (n = 15) versus LAD (n = 16) rats
      within the parietal and occipital cortices, but neither of these line differences
      reached statistical significance (p < 0.01). CONCLUSIONS: The findings suggested
      that, within the HAD and LAD replicate rat lines, the selection for alcohol
      preference did not lead to differences in functional brain activity, as measured
      with the 2-DG method.

PMID- 11329492
TI  - Quantitative autoradiography of mu-opioid receptors in the CNS of high-alcohol
      drinking (HAD) and low-alcohol-drinking (LAD) rats.
AB  - BACKGROUND: The binding of [3H]DAMGO to mu-opioid sites was measured in the CNS
      of selectively bred high-alcohol-drinking (HAD) and low-alcohol-drinking (LAD)
      rats to test the hypothesis that high alcohol preference is associated with
      higher densities of mu-opioid receptors. METHODS: Adult, alcohol-naive male HAD
      and LAD rats from replicate line 1 were decapitated and their brains frozen in
      isopentane. Brain sections were incubated with 5 nM [3H]DAMGO, and nonspecific
      binding was determined in the presence of unlabeled DAMGO. Films were exposed for
      60 days, then analyzed using quantitative autoradiography. RESULTS: The densities
      of [3H]DAMGO binding sites were measured within subregions of neocortex, limbic
      system, basal ganglia, diencephalon, and brainstem. LAD rats had significantly
      higher [3H]DAMGO binding (10-30%) than HAD rats within the anterior dorsal
      hippocampus (CA2), posterior hippocampus (dorsal CA1, and ventral CA1, CA3, and
      dentate gyrus), thalamus (medial dorsal, lateral, medial dorsal, central, ventral
      lateral, ventral medial, and ventral medial geniculate nuclei), habenula, and
      amygdala. No significant interline differences were found in the prefrontal,
      cingulate, frontal, parietal, temporal, occipital or entorhinal cortices,
      olfactory tubercle, nucleus accumbens, lateral septum, ventral tegmental area,
      hypothalamus, caudate-putamen, substantia nigra, claustrum, central gray, or
      superior colliculus. CONCLUSIONS: The present findings with the HAD and LAD lines
      do not support the hypothesis that high alcohol preference is associated with
      higher densities of CNS mu-opioid receptors. Instead, the present results, in
      combination with previously published findings, suggest that the mu-opioid system
      may play a complex role in regulating high-alcohol-drinking behavior.

PMID- 11329493
TI  - Visual p3 in female alcoholics.
AB  - BACKGROUND: The P300 (P3) component of the event related potential has been
      established as a sensitive risk marker of vulnerability to alcoholism. Most
      alcoholism studies have focused on men; recent studies indicate that women are
      equally vulnerable to developing alcoholism. METHODS: Visual P3 recorded from 31
      electrode positions was evaluated in 44 alcoholic and 60 control women, 24-50
      years of age. P3 amplitudes and latencies of the two groups were statistically
      compared using Analysis of Variance; source localization of surface amplitude
      values from each group were plotted using a low-resolution brain electromagnetic
      tomography. RESULTS: The results indicated that alcoholic women had significantly
      smaller P3 amplitudes in the frontal and central regions compared with controls.
      Source localization showed lowered activation in alcoholic women in right dorso
      lateral prefrontal cortex and the ventro-medial fronto-central regions.
      CONCLUSIONS: The results suggest that P3 is an equally sensitive endophenotypic
      marker of vulnerability to alcoholism in women. The findings are discussed in
      terms of functional and physiologic significance of the P3 amplitude in alcoholic
      women and its relationship to drinking behaviors.

PMID- 11329494
TI  - Individual differences in responses to ethanol and d-amphetamine: a within
      subject study.
AB  - BACKGROUND: In some individuals, ethanol (EtOH) produces marked stimulant-like
      subjective effects resembling those of stimulant drugs, like d-amphetamine (AMP).
      In this study, we examined the neurochemical basis of these individual
      differences by examining the same subjects' responses to both EtOH and AMP. A
      positive correlation between subjects' responses to the two drugs may suggest
      that AMP and EtOH produce their stimulant-like subjective effects by a shared
      mechanism. METHODS: Twenty-seven volunteers (17 male, 10 female), aged 21-35,
      received beverages or capsules containing EtOH 0.8 g/kg, AMP 10 or 20 mg, or
      placebo on four separate sessions in random order and under double-blind
      conditions. Various self-reported and objective drug effects were measured,
      including measures sensitive to subjective and cognitive stimulant-like effects.
      RESULTS: EtOH and AMP produced their prototypical subjective and behavioral
      effects, including increased ratings of stimulant-like subjective effects,
      increased heart rate and blood pressure, and improved vigilance performance after
      AMP and increased ratings of sedative-like subjective effects, increased heart
      rate and blood pressure, and impaired vigilance performance after EtOH.
      Consistent with previous reports, there was substantial intersubject variability
      in subjective responses to EtOH: some subjects reported primarily stimulant-like
      effects, whereas others reported primarily sedative-like effects. To examine the
      relationship between these responses to EtOH and subjects' responses to AMP,
      correlations were examined between effects of EtOH and AMP. For all subjects
      together, there was a significant positive correlation between responses to EtOH
      and 20 mg AMP on the ARCI A scale (a measure of stimulant-like subjective
      effects; r = 0.41, p < 0.05). Among only those subjects who reported primarily
      stimulant-like effects from EtOH, the correlation between EtOH and AMP was 0.64
      (p < 0.05). CONCLUSIONS: Subjects who experience pronounced stimulant-like
      effects from EtOH also report greater stimulant effects from AMP, suggesting that
      these effects may be mediated through similar mechanisms. These correlations
      between the drugs' effects were not observed on other measures, such as DSST or
      vigilance task performance or heart rate. This may indicate that these other
      effects are mediated by separate mechanisms. The study illustrates a novel
      approach to studying the neurochemical basis of drug effects.

PMID- 11329495
TI  - Sociodemographic and individual predictors of alcohol policy attitudes: results
      from a US probability sample.
AB  - OBJECTIVE: Public views on alcohol policies have facilitated legislative change.
      Given limited resources, however, policy makers and prevention advocates cannot
      make haphazard attempts to mobilize public resources. This investigation reports
      sociodemographic and individual traits predicting attitudes on alcohol policies
      designed to reduce underage alcohol consumption. Previous studies have examined
      single-item measures of alcohol policy. We examined predictors of multi-item
      scales measuring five core dimensions of alcohol policy. METHODS: A survey of
      public attitudes on alcohol policies was administered to a US national
      probability sample of 7021 adults. RESULTS: Women, infrequent drinkers, and
      adults with greater knowledge about or concern for youth exhibited the greatest
      support across five alcohol policy scales. Older adults favored policies that
      restrict alcohol use in public places, whereas younger adults favored an increase
      in alcohol taxes to address underage alcohol use. CONCLUSIONS: Individual factors
      such as alcohol use frequency and concern for youth explained larger proportions
      of variance in alcohol policy attitudes than did sociodemographic factors.
      Consistent with previous research, political orientation, parental status,
      employment status, and marital status did not predict attitudes on alcohol
      policy.

PMID- 11329497
TI  - Moderate alcohol consumption and postprandial plasma lipids in men with different
      risks for coronary heart disease.
AB  - BACKGROUND: Moderate alcohol consumption is associated with a reduced coronary
      heart disease (CHD) risk. Epidemiologic studies have provided conflicting data
      which suggests that CHD protection may be modulated or may not be modulated by a
      person's CHD risk profile. METHODS: We examined the effects of moderate alcohol
      consumption (35 g/day) on postprandial lipoprotein metabolism in two groups of
      healthy middle-aged men who had different plasma total cholesterol, triglyceride
      concentrations, and body mass index (BMI), which are three major risk factors for
      CHD; 11 men had lower plasma lipids and BMI (L-men) and 11 men had higher plasma
      lipids and BMI (H-men). The effects of alcohol on postprandial lipoprotein
      metabolism were studied in a crossover design after an acute moderate alcohol
      intake both after a period of abstinence (alcohol-free beer) and after a period
      of moderate alcohol consumption (alcohol containing beer). RESULTS: Moderate
      alcohol consumption changed plasma total cholesterol, total triglycerides, and
      HDL composition in the postprandial period. Alcohol-induced changes were
      essentially the same over time in both L-men and H-men. However, changes occurred
      at a different overall plasma concentration for total cholesterol and total
      triglycerides. Also, the postprandial response to an acute moderate alcohol dose
      after a period of abstinence seemed not to essentially differ from the response
      to an acute moderate alcohol dose after a 4-week period of moderate alcohol
      consumption. CONCLUSIONS: These results suggest that men who differ in risk for
      CHD, based on plasma lipids and BMI, but without previous or underlying disease,
      have a similar postprandial lipid response to a moderate dose of alcohol.

PMID- 11329496
TI  - Patterns of cognitive-motor development in children with fetal alcohol syndrome
      from a community in South Africa.
AB  - BACKGROUND: Even though fetal alcohol syndrome (FAS) has been reported in
      nonwestern nations, there is a paucity of information on neurodevelopment in the
      affected children from those nations. This article reports on a study of
      cognitive-motor development in a group of children with FAS from a community in
      the Western Cape Province in South Africa. METHODS: Thirty-four children with FAS
      and 34 controls from grade 1 (school entry level) classes participated. The two
      groups comprised Afrikaans-speaking children of mixed ancestry (South African
      Colored) and were matched for age, sex, and family income. The Griffiths Mental
      Development Scales were used to assess cognitive motor development of the
      participants. RESULTS: A multivariate analysis of covariance was performed to
      test the group effect on the combined Griffiths subscales adjusting for maternal
      education. The results showed a significant group effect. Follow-up analyses
      revealed that a combination of four subscales (Speech and Hearing, Performance,
      Practical Reasoning, and Eye and Hand Coordination) primarily contributed to the
      overall effect. Although there was a marginal effect on the Personal-Social
      subscale, no significant effect on the Locomotor (gross motor) subscale was
      found. CONCLUSIONS: The results showed that the FAS group was markedly deficient
      only in higher-order cognitive-motor competencies.

PMID- 11329498
TI  - Effect of chronic ethanol consumption on protective T-helper 1 and T-helper 2
      immune responses against the parasites Leishmania major and Strongyloides
      stercoralis in mice.
AB  - BACKGROUND: Chronic alcohol consumption has been associated with significant
      increases in the prevalence of infectious diseases, and it has been suggested
      that these increases are caused by a direct effect of ethanol on the immune
      response. The objective of this study was to determine whether chronic ethanol
      consumption would affect the development of protective immunity to Leishmania
      major, which is controlled by the T-helper 1 (Th1) subset of CD4 cells, and
      Strongyloides stercoralis, which is controlled by the Th2 subset. METHODS: Mice
      were fed ethanol-containing liquid diet (25% ethanol-derived calories), liquid
      isocaloric diet without ethanol, or solid chow and then exposed to either of the
      two parasites. The ability of the mice chronically consuming alcohol to eliminate
      the infections was determined, as were the levels of parasite-specific humoral
      and cellular immune responses. RESULTS: Mice chronically consuming alcohol were
      capable of eliminating both of these infections in a manner identical to the
      control mice. In addition, splenocytes from mice chronically consuming alcohol
      infected with L. major produced nitric oxide at the same levels as in control
      mice. Antibody responses were altered in a manner suggesting an increase in Th2
      immunity and a decrease in Th1 immunity in the mice chronically consuming
      alcohol. In mice chronically consuming alcohol that were infected with S.
      stercoralis, eosinophils migrated to the parasite's microenvironment, and
      antibodies were produced at levels equivalent to those seen in control mice.
      CONCLUSIONS: Mice maintained on an ethanol-containing liquid diet had some
      alteration in their ability to produce Th1 and Th2 immune responses yet were
      capable of generating unimpaired protective Th1 and Th2 responses.

PMID- 11329499
TI  - Pro- and anti-inflammatory gene expression in the murine small intestine and
      liver after chronic exposure to alcohol.
AB  - BACKGROUND: Endotoxin has been proposed to play a primary role in ALD, by
      initiating an inflammatory cascade within the liver. Although the source of these
      cytokines has been presumed to be circulating monocytes or tissue macrophages,
      ethanol-induced, nonhepatic sources of soluble mediators recently have been
      identified. One potential, but not clearly defined, extrahepatic source of
      cytokines in ALD is the intestine. In the current study, we hypothesized that
      alcohol would alter cytokine expression within the small intestine of mice
      exposed to ethanol and that LPS would alter levels of cytokine expression even
      more dramatically. METHODS: Mice were fed a modified Lieber-DeCarli liquid
      ethanol or control diet for up to 14 days prior to injecting either saline or
      LPS. Plasma alanine aminotransferase (ALT) and cytokine levels, histology, and RT
      PCR of pro- and anti-inflammatory cytokine gene expression were determined from
      distal ileum and liver samples. Translocation of intestinal bacterial flora also
      was assessed. RESULTS: Ethanol exposure upregulated basal gene expression of IL-1
      beta, TNF-alpha, IL-6, and iNOS in the distal ileum, but similar effects of
      ethanol on the liver were not observed. In contrast, LPS challenge of ethanol
      exposed mice increased intestinal gene expression of some cytokines, but
      decreased expression of others. These effects were not associated with bacterial
      translocation. Also, ethanol alone induced a modest increase in both ICAM-1 and
      TLR4 mRNA expression in the intestine, but expression of both molecules was
      inhibited in mice that received both ethanol and LPS. Finally, whereas basal
      levels of hepatic IL-11 mRNA were not elevated by exposure to ethanol, intestinal
      IL-11 mRNA levels were increased more than 100-fold. CONCLUSIONS: These studies
      are the first to show that ethanol affects cytokine gene expression in the ileum
      and identifies the ileum as a potential target for ethanol effects. In addition,
      our results suggest that IL-11 expression may be enhanced in the intestine to
      help repair or protect this organ from alcohol-induced damage. Collectively,
      these studies suggest that both pro- and anti-inflammatory soluble mediators in
      the intestine maintain and exacerbate the local hepatic response to ethanol.

PMID- 11329501
TI  - Sex and strain differences in ethanol drinking: effects of gonadectomy.
AB  - BACKGROUND: Alcohol drinking behavior in rats is known to be sexually dimorphic
      and strain-dependent. METHODS: To test whether the gonadal steroid milieu exerts
      activational effects on ethanol intake and can modulate individual sensitivity
      toward alcohol use and misuse, we examined the effects of gonadectomy on oral
      self-administration (OSA) of ethanol in male and female rats from different
      strains. After castration, animals were given continuous free choice between
      water and ethanol solutions. The ethanol concentration was progressively
      increased from 2% to 10% and maintained at 6% (the preferred concentration) for
      24 days. Ethanol solutions were then withdrawn for 9 days. During the second
      phase of free-choice drinking, the ethanol concentration was gradually increased
      every 4 days by the following amounts, in order as listed: 6%, 12%, and 24%.
      RESULTS: Our results confirm both gender and strain differences in ethanol
      drinking: females exhibited higher ethanol intake than males, and the WKHA strain
      drank more than the WKY and SHR strains. However, except for a small decrease in
      ethanol drinking during the acquisition of ethanol OSA in males after castration,
      no clear-cut difference was found between gonadectomized and sham-operated
      animals during the maintenance of ethanol OSA behavior. CONCLUSIONS: These data
      suggest that gender and strain differences observed are insensitive to gonadal
      steroids during adulthood, and that different sensitivities to the effect of
      gonadal steroids do not explain the sex x strain interaction observed in ethanol
      drinking.

PMID- 11329500
TI  - Regulation of milk intake after exposure to alcohol in mothers' milk.
AB  - OBJECTIVE: Contrary to the folklore which claims that drinking alcohol during
      lactation benefits both mother and infant, previous research in our laboratory
      revealed that breastfed infants consumed significantly less milk during the
      immediate hours after their mothers' consumption of an alcoholic beverage.
      Because breastfed infants are clearly capable of regulating milk intake, the
      present study tested the hypothesis that infants would compensate for the
      diminished milk intake if their mothers then refrained from drinking alcohol.
      METHODS: A within-subjects design that controlled for time of day was implemented
      because of the great individual and daily variation in both milk composition and
      intake. To this end, 12 exclusively breastfed infants and their mothers were
      tested on 2 days separated by 1 week. Each woman drank a 0.3 g/kg dose of alcohol
      in orange juice on one testing day and orange juice alone on the other; the order
      was counterbalanced. The infants' behaviors were monitored for the next 16 hr,
      the first 4 hr of monitoring on each test day occurred at the Monell Center. The
      infants fed on demand and immediately before and after each feeding, infants were
      weighed without a change in clothing. RESULTS: Consistent with previous findings,
      infants consumed significantly less milk during the 4 hr immediately after
      exposure to alcohol in mothers' milk compared with the control condition.
      Compensatory increases in intake were then observed during the 8 to 16 hr after
      exposure when mothers refrained from drinking alcohol. CONCLUSIONS: These
      findings demonstrate that short-term exposure to small amounts of alcohol in
      mothers' milk produces distinctive changes in the infants' patterns of feeding.

PMID- 11329502
TI  - Zinc supplementation does not attenuate alcohol-induced cerebellar Purkinje cell
      loss during the brain growth spurt period.
AB  - BACKGROUND: Alcohol-induced zinc deficiency is one of the mechanisms proposed as
      a cause of developmental brain damage associated with fetal alcohol syndrome. It
      is known that alcohol exposure during the brain growth spurt period leads to
      cerebellar Purkinje cell loss. Therefore, this study examined whether zinc
      supplementation was capable of preventing alcohol-induced Purkinje cell loss in
      the cerebellar vermis in a neonatal rat model system. METHODS: Sprague-Dawley rat
      pups were given alcohol (EtOH; 4.5 g/kg/day), zinc (Zn; 0.54 mg/ml diet; [10
      times the regular diet Zn concentration]), or both from postnatal days (PD) 4
      through 9 using the artificial-rearing paradigm. A gastrostomy control (GC) and a
      suckle control group (SC) also were included. All pups were killed on PD 10.
      Following perfusion, the cerebellar vermis was dissected and processed for
      stereological cell counting. The total number of Purkinje cells and the volume of
      the cerebellar vermis were determined. RESULTS: Alcohol produced a significant
      loss of Purkinje cells compared with that in the GC group (no EtOH and no Zn
      supplement). The zinc supplementation had no effect in attenuating alcohol
      induced Purkinje cell loss in the cerebellar vermis. In fact, the serum zinc
      concentration data indicated higher zinc concentrations following either EtOH or
      Zn treatment. Interestingly, the GC group showed a significantly lower zinc
      concentration compared with the SC group, even though no significant difference
      in Purkinje cell numbers was observed between these two control groups.
      CONCLUSION: These findings indicate that alcohol exposure during the third
      trimester equivalent did not result in zinc deficiency in this neonatal rat model
      system, nor did zinc supplementation rescue the alcohol-induced Purkinje cell
      loss in the cerebellar vermis. These findings showed clearly that the serum zinc
      concentration was not correlated with Purkinje cell loss, suggesting that alcohol
      induced loss of cerebellar Purkinje cells in this neonatal rat model system is
      independent of the availability of serum zinc.

PMID- 11329503
TI  - Ethanol dependence has limited effects on GABA or glutamate transporters in rat
      brain.
AB  - BACKGROUND: Neuroadaptations of GABAergic and glutamatergic systems appear to
      play an important role in both the acute as well as chronic effects of ethanol.
      Chronic ethanol intake leads to the development of ethanol tolerance and
      dependence that is associated with a decrease in GABAergic and an increase in
      glutamatergic function. The present report assessed the involvement of GABA and
      glutamate transporters in the chronic ethanol-induced adaptations of these two
      neuronal systems. METHODS: Male and female rats were made ethanol dependent by 2
      week administration of ethanol in a liquid diet. Levels of GABA (GAT-1, GAT-3)
      and glutamate (GLT-1, EAAC-1) transporters were assayed by immunoblotting.
      Transporter function was assessed by [3H]GABA and [3H]glutamate uptake assays.
      RESULTS: Ethanol dependence did not alter levels of GABA or glutamate
      transporters in cerebral cortex compared with pair-fed control values. There were
      increases in some, but not all, transporter levels in hippocampus and
      hypothalamus with the development of ethanol dependence. A decreased rate of
      uptake was observed for GABA in cerebral cortex. There was no change in maximal
      GABA uptake or in glutamate uptake (Vmax). CONCLUSIONS: These results suggest
      that alterations in GABA and glutamate transporters have only a limited role in
      neuroadaptations to chronic ethanol intake in rats. However, the observed
      alterations were region-specific, supporting the complex responses to chronic
      ethanol exposure and suggesting that neuroadaptations of GABAergic and
      glutamatergic systems vary across the brain.

PMID- 11329504
TI  - Ethanol effects on nitric oxide production in cerebral pial cultures.
AB  - BACKGROUND: Although alcohol abusers are known to have higher incidences of
      hemorrhagic cerebrovascular diseases, it is not known whether these changes are
      associated with ethanol (EtOH) action on nitric oxide (NO) production in the
      cerebrovascular cells. The purpose of this study was to examine the effects of
      EtOH treatment on basal and cytokine-induced NO production in cortical pial
      cultures. METHODS: Cell cultures for this study included murine primary pial
      vascular cells, primary glial cells and cortical neurons. These cells were
      exposed to cytokines or EtOH for 24 to 48 hr. The culture media were used for
      measurement of nitrite, as an indication for NO release, and lactate
      dehydrogenase (LDH), as an index of cell membrane integrity. In addition,
      immunocytochemical determinations were carried out to identify cell types and to
      assess inducible nitric oxide synthase (iNOS). RESULTS: Exposure of primary pial
      vascular cultures to cytokines that consisted of interleukin-1 beta (IL-1 beta;
      250 pg/mL) and interferon-gamma (IFNgamma; 2 ng/mL) or to EtOH (50 to 100 mM) for
      24 to 48 hr significantly elevated NO production. NO production could be
      attenuated by N-nitro-L-arginine (N-arg), a nonspecific NOS inhibitor, or
      aminoguanidine (AG), an iNOS inhibitor. Increased iNOS immunoreactivity was
      observed in cytokines- or EtOH-treated pial cells. When pial cells were
      cocultured with cortical neurons, prolonged EtOH exposure led to a large increase
      in NO production as well as LDH release. However, this increase was not observed
      in pial culture alone or in mixed cortical culture. Nevertheless, inhibition of
      NO production with N-arg or AG did not alter the EtOH-induced LDH release in the
      pial cells cocultured with cortical neurons. CONCLUSION: These results show that
      EtOH exposure led to increased production of NO in primary pial cell culture. In
      mixed culture that contained cortical neurons and pial cells, EtOH induced
      increase in NO as well as LDH release, which is an indication of loss of cell
      membrane integrity. However, EtOH-mediated LDH release in mixed cortical pial
      cultures was not a consequence of the increase in NO production by these cells.
      Studies that use mixed cortical-pial cultures may provide a unique in vitro
      system for examining the interactions among glial cells, neurons, and
      cerebrovascular cells.

PMID- 11329505
TI  - Removal of glutathione produces apoptosis and necrosis in HepG2 cells
      overexpressing CYP2E1.
AB  - BACKGROUND: Previous studies have shown that addition of ethanol, iron, or
      arachidonic acid to HepG2 cells expressing CYP2E1 produced a loss in cell
      viability and caused apoptosis. These effects were enhanced when cellular reduced
      glutathione (GSH) levels were lowered by treatment with buthionine sulfoximine
      (BSO). Overexpression of CYP2E1 in HepG2 cells could produce toxicity even in the
      absence of added toxin after BSO treatment. Studies were carried out to
      characterize this CYP2E1-and BSO-dependent toxicity. METHODS: HepG2 cells
      expressing CYP2E1 were treated with BSO for 1 to 4 days, and various parameters
      associated with apoptosis and cell viability were assayed. RESULTS: Treatment of
      cells expressing CYP2E1 (E47 cells) with BSO resulted in apoptosis as well as
      necrosis. The apoptosis and necrosis were independent of each other. No toxicity
      was found with control HepG2 cells or HepG2 cells expressing CYP3A4 instead of
      CYP2E1 under these conditions. The antioxidant trolox partially prevented the
      apoptosis and necrosis, whereas diallylsulfide, a CYP2E1 inhibitor, was fully
      protective. The activity of caspase 3, but not caspases 1, 8, or 9, was increased
      in the BSO-treated E47 cells, and an inhibitor of caspase 3 prevented apoptosis.
      Damage to mitochondria appears to play a role in the CYP2E1- and BSO-dependent
      toxicity, because mitochondrial membrane potential was decreased and cyclosporin
      A, an inhibitor of the mitochondrial membrane permeability transition, prevented
      the apoptosis and the necrosis. The fall in membrane potential was prevented by
      trolox and diallylsulfide, suggesting damage to the mitochondria by CYP2E1
      derived reactive oxygen species. CONCLUSIONS: These results indicate the critical
      role of GSH in protecting against CYP2E1-mediated oxidative stress and that
      mitochondria may be a target for CYP2E1-derived reactive oxygen species, and
      suggest that interactions between CYP2E1, mitochondria, and altered GSH
      homeostasis may play a role in alcohol-induced liver injury.

PMID- 11329506
TI  - The metabolic and nutritional response to critical illness.
AB  - The metabolic response to critical illness promotes catabolism, which mobilizes
      substrates for energy. Initially the hypothalamic-pituitary-adrenal axis is
      stimulated, but later there appears to be anterior pituitary depression. Despite
      this, the early increase in plasma cortisol levels is usually maintained by means
      independent of (falling) corticotropin levels. Some patients, however, develop
      acute adrenal insufficiency and appear to benefit from replacement exogenous
      glucocorticoid. However, identifying such patients is often difficult. The
      replacement of other deficiencies may not be in the patients' interests. For
      example, leptin, a stress-related hormone, has multiple effects, some seemingly
      advantageous and others detrimental in critical illness. Its overall influence
      and significance remains unclear.The health of gut mucosa and the inflammatory
      response might be improved or influenced to the (presumed) benefit of the patient
      by agents such as glutamine, arginine, some eicosanoids, and exogenous nucleic
      acids. Such "immunonutrition" appears to improve mortality and other measures of
      outcome in surgical intensive care unit patients and those with sepsis.

PMID- 11329507
TI  - How to feed patients with renal dysfunction.
AB  - Renal dysfunction is common in critically ill patients and its presence has, in
      the past, posed serious challenges to nutritional support. Such challenges were
      due to the increased azotemia induced by protein or amino acid administration,
      the fluid overload caused by the administration of nutrients, and the
      difficulties associated with the control of these complications by means of
      conventional dialytic techniques.The development and increasing application of
      continuous renal replacement therapy has removed such concerns, because control
      of azotemia and fluid balance can be predictably and reliably achieved in all
      patients. Accordingly, the presence of renal failure should in no way influence
      the amount or type of nutritional support administered to a critically ill
      patient. We recommend that approximately 30-35 kCal/kg/d be administered
      enterally and begun within the first few hours of admission to the intensive care
      unit, and that protein intake be kept in the 1.5-2 g/kg/d range.Accumulating
      evidence also suggest that immune-enhancing enteral preparations decrease the
      duration of hospital stay, the number of infections, and perhaps mortality. Such
      preparations should be used in these patients. Finally, adequate vitamin and
      trace element supplementation is recommended to counterbalance the decrease in
      antioxidants and the loss of some vitamins during continuous renal replacement
      therapy. Available evidence suggests that if these steps are applied as part of a
      protocol-based approach to the nutritional support of patients with renal
      failure, morbidity and perhaps mortality can be significantly decreased.

PMID- 11329508
TI  - How to feed patients with sepsis.
AB  - Sepsis is associated with profound catabolism and hypermetabolism that complicate
      provision of nutritional support. These metabolic changes are caused by
      inflammatory mediators involved in the septic process and cannot be reversed by
      nutritional means. High protein isocaloric nutritional regimens are recommended
      if possible, in association with aggressive measures to control the sepsis.
      However, nutritional therapy and its complications may also affect the incidence
      and course of sepsis. Hyperglycemia and conventional intravenous fat emulsions
      have been shown to increase susceptibility to infection. Enteral nutrition is
      associated with fewer infectious complications than parenteral nutrition, at
      least in severely injured patients. Recently nutritional formulations have been
      introduced that contain novel substrates that enhance various aspects of
      immunity. Several studies have suggested that this immunonutrition reduces
      infection risk in the critically ill, and preliminary findings suggest it may
      even have an effect on survival in sepsis.

PMID- 11329509
TI  - Nutritional support in sepsis: still skeptical?
AB  - The immediate metabolic response to a septic challenge is probably adaptive,
      meaning that nutritional interference, mainly via the parenteral route, during
      this early phase of instability can do more harm than good. During the later
      phases, a gradual increase in enteral nutrition, at the expense of parenteral
      nutrition, combined with the administration of nutraceuticals such as glutamine
      and omega-3 fatty acids, can counteract wasting and modulate the complex
      inflammatory response and immunosuppression associated with sepsis. In these
      times of scarce resources, there is an urgent need to clearly document the
      efficacy of immuno/pharmaconutrients, individually and in combination, enterally
      or parenterally, before proposing them for routine management of septic patients
      in the intensive care unit.

PMID- 11329510
TI  - When and how should we do a tracheostomy?
AB  - Tracheostomy is one of the most common surgical procedures in the intensive care
      unit. Since the introduction of percutaneous techniques, tracheostomy has become
      increasingly popular. The technique is relatively easy, and the early and late
      complication rates are relatively low.It is unknown at which moment tracheostomy
      can best be performed in the translaryngeally intubated patient. There are
      theoretic arguments for both early and late tracheostomy. The excellent results
      of percutaneous tracheostomy may influence the decision to perform a tracheostomy
      rather early, but prospective randomized studies are required to gather the
      necessary evidence.

PMID- 11329511
TI  - Management of acute pancreatitis in the intensive care unit.
AB  - Acute pancreatitis is a disease with a variety of symptoms. In patients in whom
      the disease takes a more severe course, stabilization is mandatory, often in a
      high dependency unit or intensive care unit. When the pancreatitis is of biliary
      origin and cholangitis and cholestatic changes are proven or suspected, an
      endoscopic cholangiopancreaticography is indicated. Aggressive organ support and
      continuation of the prophylactic antibiotics are the mainstay of treatment. When
      infected necrosis has been proven by CT-guided fine needle biopsy, surgical
      necrotectomy and debridement with drainage are necessary. Enteral feeding is
      superior to parenteral feeding even in situations of severe pancreatitis. Further
      investigation into the role of selective digestive tract decontamination, by
      controlled randomized trials, is needed.

PMID- 11329512
TI  - Damage control in trauma surgery.
AB  - The technique or approach of damage control surgery in trauma is not new; packing
      liver injuries has been an accepted treatment strategy for some time. What is new
      is the realization that an abbreviated laparotomy, or completion of only the
      essential portions of the operation, is often the best treatment for the patient
      as a whole. Recent developments include strategies in the operating room and the
      intensive care unit to manage patients undergoing trauma laparatomy, including
      prevention of hypothermia, methods to accurately assess resuscitation status with
      right ventricular catheters and measurements of end-organ perfusion, and
      recognition of abdominal compartment syndrome, with emphasis on prevention.

PMID- 11329513
TI  - Current recommendations for neurotrauma.
AB  - Diagnostic and monitoring procedures for patients with head injury are aimed at
      early detection of mass lesions and secondary insults. Our therapeutic approach
      is based on our understanding of pathophysiologic mechanisms that cause secondary
      brain damage, and includes evacuation of mass lesions and prevention of secondary
      insults. Basic research has greatly increased our knowledge of these
      pathophysiologic mechanisms and has prompted the development of many
      neuroprotective agents, targeted to selected mechanisms. Unfortunately, it has
      proved difficult to demonstrate the benefit of such agents in the overall
      population of head-injured patients. Clinical research has emphasized the
      importance of ischemia in head injury and has demonstrated the deleterious effect
      of secondary insults on outcome. Medical management of patients with head injury
      has consequently focused on prevention of secondary insults, treatment of raised
      intracranial pressure, and maintenance of adequate cerebral perfusion pressure.
      The introduction of new monitoring techniques in head-injured patients offers the
      possibilities of more targeted therapy in individual patients, in contrast to the
      current practice of a staircase approach to treatment of raised intracranial
      pressure.In the US, an evidence-based approach has resulted in the wide
      acceptance of general principles, but at the same time highlighted the lack of
      hard evidence for the use of many therapeutic modalities. Practical guidelines,
      developed and published by the European Brain Injury Consortium, are based on
      expert opinion and consensus. Surveys have shown considerable variation in
      monitoring techniques and treatment. There is still considerable need for further
      improvements, both from a medical scientific perspective and from an
      organizational aspect. Particularly relevant are early resuscitation and
      stabilization at the scene of the accident, the organization of emergency
      services, admission policy to the intensive care unit, and improved policy for
      early identification of patients with operable intracranial hematoma. Further
      dissemination and general acceptance of already published guidelines may be
      expected to significantly improve care in head injury.

PMID- 11329514
TI  - Decision analysis models and simulations in critical care medicine.
AB  - Because clinical trials have frequently not been performed for many clinical
      problems in critical care and other clinical disciplines, models and simulations
      are often used to quantitatively assess important diagnostic, therapeutic, and
      cost-effectiveness issues. This article presents a brief overview of decision
      analysis models, one of the most common methodologies used to develop disease
      models and simulations, and their applications to problems in critical care
      medicine.

PMID- 11329515
TI  - Critical care pharmacotherapy: issues and approaches.
AB  - Critically ill patients are a unique group with potentially altered
      pharmacokinetic and pharmacodynamic characteristics. The provision of optimal
      care to these patients is best accomplished via an intensivist-led
      multidisciplinary team. Included on this team should be a pharmacist specifically
      trained in critical care. The presence of a critical care pharmacist has been
      documented to not only decrease the cost of drug use in this setting but to
      improve the quality of care as well. Further investigations should focus on the
      impact of these interventions on outcomes. These will include pharmacoeconomic
      outcomes as well as their impact on other parts of the healthcare system in order
      to avoid cost shifting and improve morbidity and mortality.

PMID- 11329516
TI  - Remote access to critical care.
AB  - As we all begin to focus more on errors in medicine, telemedicine applications
      will expand. Remote access to experts will be required. Although telemedicine has
      always existed as a component of medicine, it was usually designed for niche
      areas. Telemedicine consists of information sharing between at least two
      physically and geographically disparate sites for educational or health purposes.
      Although telemedicine in the intensive care unit may at first seem absurd to many
      clinicians, most care providers have, in fact, used some form of telemedicine to
      provide care for decades. All of us have managed patients by telephone
      communication with nurses, residents, or other physicians. Besides augmenting
      routine care in the intensive care unit, telemedicine is providing essential
      tools that improve the efficiency of health care communication and add safety for
      the health care provider by making health care available under less than ideal
      circumstances, such as a terrorist attack with biologic weapons. The future
      appears quite bright for telemedicine systems, but much work is still required.
      How payers, lawyers, and ethicists view telemedicine is not yet completely
      understood. As intensivists, we should expect our practice to be directly
      impacted by this maturing technology. We should wholeheartedly embrace it and
      help lead its use in this new millennium.

PMID- 11329517
TI  - Update from funders. Center for Primary Care Research and Agency for Health Care
      Research and Quality.

PMID- 11329518
TI  - What are fairness and consistency in a national pharmacy benefit?

PMID- 11329519
TI  - A dog's breakfast: prescription drug coverage varies widely across Canada.
AB  - BACKGROUND: Each province in Canada independently assesses drugs for their
      reimbursement eligibility. Publicly funded access to specific drugs is therefore
      dependent on province of residence. OBJECTIVE: Evaluate the variability of access
      and its determinants for publicly available prescription drugs across Canada, and
      discuss the feasibility of implementing a national plan. METHODS: For a sample of
      58 drugs receiving Health Protection Branch approval in Canada between 01/01/1996
      and 12/31/1997, all provinces were surveyed about their formulary
      inclusion/exclusion decision. Kappa values were estimated to measure concordance
      between provincial coverage decisions. Logistic analysis using Generalized
      Estimating Equations was used to assess the impact of key features of provincial
      plans on the decision. RESULTS: Among the 58 drugs, 5 (9%) were included in all
      10 and 14 (24%) by at least 8 provincial formularies. None were excluded by all
      the provinces. Concordance rates among provinces were low (overall kappa-like
      statistic = 0.20 and range of pairwise kappa = -0.11 to 0.64). Logistic
      regression showed that therapeutic category, price ratio to comparator, the
      integration of public with private coverage, and the existence of ability-to-pay
      criteria were significant determinants of the inclusion decision. CONCLUSIONS:
      Findings show that public access to the same prescription medications differs
      widely across provinces. If Canada were to adopt a "National" plan without
      disrupting current individual prescriptions, all currently funded drugs in each
      province would have to be "grandfathered" and included in the new National
      formulary. Such an all-inclusive list would also make such a plan unaffordable.

PMID- 11329520
TI  - Posttraumatic concerns: a patient-centered approach to outcome assessment after
      traumatic physical injury.
AB  - BACKGROUND: Approximately 2.5 million Americans are admitted to the hospital
      after traumatic physical injury each year. Few investigations have elicited
      patients' perspectives regarding posttraumatic outcomes. OBJECTIVE: To identify
      and categorize physically injured trauma survivors' posttraumatic concerns.
      RESEARCH DESIGN: Prospective longitudinal investigation; trauma survivors were
      interviewed during the post-injury hospitalization and again 1, 4, and 12 months
      after the trauma. SUBJECTS: Ninety-seven, randomly selected, English speaking,
      hospitalized survivors of motor vehicle-crashes or assaults. MEASURES: At the end
      of each interview patients were asked, "Of all the things that have happened to
      you since you were injured, what concerns you the most?" Using an iterative
      process and working by consensus, investigators categorized patient concerns in
      content domains. Concern domains were then compared with established measures of
      posttraumatic stress disorder (PTSD) symptoms and limitations in physical
      functioning. RESULTS: Seven categories of posttraumatic concerns were identified.
      During the course of the year, 73% of patients expressed physical health
      concerns, 58% psychological concerns, 53% work and finance concerns, 40% social
      concerns, 10% legal concerns, 10% medical concerns, and 20% uncodable concerns.
      Rater agreement on concern categorization was substantial (kappa = 0.72). The
      mean number of concerns expressed per patient gradually decreased over time (1
      month mean = 1.51; 12 month mean = 1.26) and resembled the trajectories of PTSD
      symptoms and functional limitations. CONCLUSIONS: The concerns of physically
      injured trauma survivors are readily elicited and followed up during the course
      of the year after injury. Open-ended inquiry regarding posttraumatic concerns may
      complement standardized outcome assessments by identifying and contextualizing
      the outcomes of greatest importance to patients.

PMID- 11329521
TI  - Effect of vaccination by community pharmacists among adult prescription
      recipients.
AB  - BACKGROUND: Millions of doses of influenza vaccine are administered each year in
      the United States at nontraditional sites and by nontraditional vaccine
      providers. Pharmacists are increasingly becoming vaccine providers. OBJECTIVES:
      To measure association between availability of pharmacist-immunizers and
      immunization delivery to adult prescription recipients, and the relative
      contributions of various types of vaccine providers. RESEARCH DESIGN: Mailed
      survey in spring 1999, contrasting adults in urban Washington State, where
      pharmacists administer vaccines, to adults in urban Oregon, where pharmacists did
      not. SUBJECTS: Cluster sample based on October 1998 prescription records
      suggesting need for influenza vaccine, derived from 24 community pharmacies
      belonging to one pharmacy chain. MEASURES: Vaccination status and choice of
      vaccine provider. RESULTS: Influenza vaccination rates among respondents 65 years
      or older increased 4.7% more in Washington than in Oregon between 1997 and 1998
      (P = 0.20). The net increase in influenza vaccination rate among younger
      respondents taking indicator medications for chronic diseases for which influenza
      vaccination is recommended was 10.6% (P = 0.05). Among respondents unvaccinated
      against influenza in 1997, the 1998 influenza vaccination rate was 34.7% in
      Washington, compared with 23.9% in Oregon (P = 0.01). CONCLUSIONS: Vaccine
      delivery by pharmacists is associated with higher rates of vaccination among
      those younger than 65 taking indicator medications medications for chronic
      diseases, as well as prescription recipients unvaccinated against influenza in
      the previous year.

PMID- 11329522
TI  - Are better ratings of the patient-provider relationship associated with higher
      quality care for depression?
AB  - BACKGROUND: The interpersonal patient-provider relationship (PPR) is an essential
      part of health care quality, particularly for patients with depression, yet
      little is known neither about how to measure this relationship nor about its
      association with quality of care. OBJECTIVES: To evaluate properties of patient
      rating measures, understand the relation between 2 types of ratings, and
      determine the association of ratings with quality depression care. SETTING AND
      PARTICIPANTS: 1,104 patients with current depressive symptoms and lifetime or 12
      month disorder identified through screening 27,332 consecutive primary care
      visitors in 6 managed care organizations participating in Partners in Care (PIC).
      DESIGN: Cross-sectional analysis of 18-month data (collected in 1998) after the
      start of PIC depression quality improvement (QI) interventions (in which clinics
      were randomized to 1 of 2 QI interventions or usual care). MEASURES: Patient
      ratings of the interpersonal relationship with the primary care provider and
      satisfaction with health care, and quality of depression care indicators.
      ANALYSIS: Factor analysis and multitrait scaling to evaluate the psychometric
      properties of multiitem constructs and analysis of covariance to evaluate
      associations between patient ratings and quality. RESULTS: Patient ratings had
      high internal consistency and met criteria for discriminant validity tapping
      unique aspects of care. Patients receiving quality care, especially for
      medication use, had significantly higher ratings of the interpersonal
      relationship (by 22% to 27% of a SD) and were more satisfied (by 26% to 34% of a
      SD) than patients who did not receive quality care. CONCLUSIONS: Ratings of the
      interpersonal relationship and satisfaction measure distinct aspects of care and
      are positively associated with quality care for depression.

PMID- 11329523
TI  - Sociodemographic differences in the receipt of colorectal cancer surveillance
      care following treatment with curative intent.
AB  - BACKGROUND: Despite limited evidence of its effectiveness, most guidelines
      recommend colorectal cancer survivors undergo posttreatment surveillance care.
      This article describes the posttreatment use of colon examinations,
      carcinoembryonic antigen (CEA) testing, and metastatic disease testing among a
      managed care population. METHODS: Two hundred fifty-one patients with colorectal
      cancer enrolled in a managed care organization at diagnosis (1/1/90-12/31/95) and
      treated with curative intent. Patients were identified via a Cancer Registry
      maintained by a large group practice. Cumulative incidences of service receipt
      were estimated using actuarial (Kaplan-Meier) survival analyses. Co- Proportional
      Hazard Models were used to evaluate the relation of patient sociodemographic and
      clinical characteristics to service receipt. Average 8-year medical care
      expenditures were calculated. RESULTS: Within 18 months of treatment, 55% of the
      cohort received a colon examination, 71% received CEA testing, and 59% received
      metastatic disease testing. Whites were more likely than minorities to receive
      CEA testing (RR = 1.47, P = 0.04) and tended to be more likely to receive a colon
      examination (RR = 1.43, P = 0.09). As the median household income of a patient's
      zip code of residence increased, so too did the likelihood of colon examination
      and metastatic disease testing receipt (RR = 1.09, P = 0.03 and RR = 1.12, P
      <0.01, respectively). Average 8-year medical care expenditures among the cohort
      were $30,247. CONCLUSIONS: Among a population with financial access to care,
      differences were found in the receipt of colorectal cancer surveillance care by
      race and income. Additional investigations are needed to understand why
      minorities and those residing in low-income areas are less likely to receive
      surveillance care.

PMID- 11329524
TI  - Impact of clinical trials on the cost of cancer care.
AB  - BACKGROUND: Empirical evidence on the economic impact of cancer clinical trials
      is in short supply, but it is widely assumed that clinical trials add at least
      10% to overall costs. OBJECTIVES: To estimate how much, if at all, trial
      enrollment increases the use of scarce resources in treating breast, lung,
      lymphoma, and ovarian cancer patients. RESEARCH DESIGN: A profile of the
      cumulative charges for all inpatient and outpatient hospital care received by a
      sample of patients over an observation period beginning at diagnosis and
      continuing for upwards of 44 months postdiagnosis. Patients are classified by
      whether they were enrolled on an IRB-sanctioned research protocol and, if so, by
      the type of protocol. Both univariate and multivariate statistical tests are
      conducted to appraise whether cumulative charges differ between patients who were
      enrolled on key types of protocols and those who were not. SUBJECTS:
      Approximately 1,900 breast, lung, lymphoma, and ovarian cancer patients treated
      at a single center. MEASURES: Clinical endpoints and demographic, disease, and
      therapy characteristics of patients that drive treatment costs. RESULTS:
      Controlling for demographic and disease characteristics, initial therapy, and key
      endpoints, the net effect of trial participation on cumulative charges for
      hospital inpatient and outpatient care is never significantly positive at
      conventional confidence limits. This result is found for each of the four patient
      groups and three types of protocols encompassed by this analysis. CONCLUSIONS:
      Support for clinical trials by health care payers does not necessarily risk
      adding significantly to the cost of cancer care.

PMID- 11329525
TI  - Trends in hormonal management of prostate cancer: a population-based study in
      Ontario.
AB  - OBJECTIVE: To provide a population-based description of current practice in the
      use of hormonal management of prostate cancer. DESIGN,SETTING & PARTICIPANTS: All
      men in Ontario, Canada, age 65 and older, with confirmed prostate cancer starting
      maintained hormonal therapy, from July 1992 through December 1998 (11,435
      patients). Data sources included the provincial drug benefit plan, hospital
      services data, and Ontario Cancer Registry. OUTCOME MEASURES: Rates and trends in
      the use of: surgical or medical castration; total androgen blockade (TAB); and
      monotherapies based on steroidal or nonsteroidal antiandrogens. RESULTS: In 5.5
      years, use of 'standard' therapy based on surgical or medical castration alone
      dropped from 36% to 26% of patients, while the use of TAB doubled from 22% to
      41%. Approximately 15% of patients received nonsteroidal antiandrogens without
      evidence of therapy aimed at central androgen blockade. Marked regional
      differences were observed and not explained by patient age or practitioner
      specialty. CONCLUSIONS: New hormonal therapies for prostate cancer have
      implications in terms of disease control, patient survival, side effects, and
      costs. Rapid growth in prescribing of antiandrogens may represent an unnecessary
      expense for public or private payers, and observed regional differences likely
      reflect lack of consensus on the relative merit of TAB. Patients and
      practitioners must have current information on the advantages and disadvantages
      of different therapeutic options, and quality-of life, particularly with respect
      to emerging drug therapies.

PMID- 11329526
TI  - Clinical importance of provider-reported HIV symptoms compared with patient
      report.
AB  - BACKGROUND: Although the patient experiences the symptoms, only symptoms that
      providers recognize and report "count" in most clinical and research settings.
      Reliance upon provider-report has been justified by the claim that providers
      report only "clinically important" symptoms. OBJECTIVE: To determine whether
      provider-reported symptoms constitute a more "clinically important" subset of
      patient-reported symptoms in HIV infection. DESIGN: Secondary analyses of AIDS
      Clinical Trials 175 (ACTG 175), a randomized controlled trial of combination
      antiviral therapy among patients with moderate HIV disease. SETTING: Large,
      multicenter study. PATIENTS: 1,262 patients who participated in the health
      related quality of life (HRQOL) sub-study and for whom providers completed
      symptom forms. MEASUREMENTS: Patient- and provider-reported symptoms, HRQOL, risk
      of recent hospitalization, survival, CD4 cell count, and plasma HIV-1 RNA levels.
      RESULTS: On average, providers reported 3-fold fewer symptoms than patients did,
      but the degree of under report varied by symptom. When patient-reports were used
      as a gold standard, provider-reports demonstrated poor sensitivity (mean 0.25)
      and good specificity (mean 0.96). Agreement beyond chance was fair (mean kappa
      0.35) and did not improve when weighted by symptom severity. Site specific
      variation was greater for provider than for patient-reported symptoms (R2: 0.15
      and 0.05 respectively). Patient-reported symptoms were substantially more
      strongly associated with the physical health scale and all HRQOL subscales than
      provider-reported symptoms (P <0.0001). Patient-reported symptoms were equally
      strongly associated with survival (P >0.50) and recent hospitalization as
      provider-reported symptoms (P >0.48). Of note, patient-reported symptoms were
      independently associated with survival and recent hospitalization after
      adjustment for CD4 cell count and plasma HIV-1 RNA levels (P <0.05). CONCLUSIONS:
      Provider-reported symptoms are not a more clinically important subset of patient
      reported symptoms. Patient-reported symptom checklists are likely to be more
      complete and more strongly associated with HRQOL. Further, patient-reported
      symptoms are as related to recent hospitalization and survival as provider
      reported symptoms. An HIV specific, patient-completed symptom checklist might
      substantially improve symptom reporting for adverse drug event monitoring,
      clinical management and medical research.

PMID- 11329527
TI  - Apoptosis and asbestos-induced disease: Is there a connection?

PMID- 11329528
TI  - Left ventricular diastolic heart failure with normal left ventricular systolic
      function in older persons.
AB  - Underlying causes and precipitating causes of congestive heart failure (CHF)
      should be treated when possible. Older persons with CHF and normal left
      ventricular (LV) ejection fraction should have maintenance of sinus rhythm,
      treatment of hypertension and myocardial ischemia, slowing of the ventricular
      rate below 90 beats/minute, and reduction of salt overload. First-line drug
      treatment in the management of these persons is the use of loop diuretics
      combined with beta blockers as tolerated. Angiotensin-converting enzyme (ACE)
      inhibitors should be administered if CHF persists despite diuretics and beta
      blockers. If persons are unable to tolerate ACE inhibitors because of cough,
      rash, or altered taste sensation, angiotensin II type 1 receptor antagonists
      should be given. If CHF persists despite diuretics, beta blockers, and ACE
      inhibitors or the person is unable to tolerate beta blockers, ACE inhibitors, and
      angiotensin II type 1 receptor antagonists, isosorbide dinitrate plus hydralazine
      should be administered. Calcium channel blockers should be used if CHF persists
      despite administration of diuretics and the person is unable to tolerate beta
      blockers, ACE inhibitors, angiotensin II type 1 receptor antagonists, and
      isosorbide dinitrate plus hydralazine. Digoxin, beta blockers, verapamil, and
      diltiazem may be used to slow a rapid ventricular rate in persons with
      supraventricular tachyarrhythmias. Digoxin should not be used in persons with CHF
      in sinus rhythm with normal LV ejection fraction.

PMID- 11329529
TI  - The controversial role of deferiprone in the treatment of thalassemia.
AB  - The role of the orally active iron (Fe) chelator deferiprone in the treatment of
      beta-thalassemia remains a controversial subject. Despite initial studies showing
      high Fe chelation efficacy in vitro and also in animals and human subjects,
      several latter studies have not been so successful. In fact, it has been reported
      in several clinical trials that deferiprone after long-term treatment had either
      little effect or actually increased hepatic Fe loading. In addition, an increase
      in liver fibrosis was noted in one study. However, more recently, results by
      other investigators have suggested that the drug may be used under some
      circumstances without marked toxicity. In particular, it has been demonstrated
      that the combination of deferoxamine (DFO) and deferiprone results in more Fe
      excretion than when either chelator is used alone. Moreover, a combination of
      both drugs led to a decrease in deferiprone-mediated toxicity. Other studies
      performed in patients for up to 10 years showed no progressive fibrosis after
      deferiprone therapy, while a possible trend toward increasing fibrosis was noted
      in another investigation. Additional studies using larger numbers of deferiprone
      treated patients are essential to determine the efficacy and safety of this drug,
      particularly in relation to the development of fibrosis. The present review
      discusses the possible role of deferiprone in the treatment of Fe overload.

PMID- 11329530
TI  - Asbestos causes apoptosis in alveolar epithelial cells: role of iron-induced free
      radicals.
AB  - Asbestos causes asbestosis and malignancies by mechanisms that are not fully
      understood. Alveolar epithelial cell (AEC) injury by iron-induced reactive oxygen
      species (ROS) is one important mechanism. To determine whether asbestos causes
      apoptosis in AECs, we exposed WI-26 (human type I-like cells), A549 (human type
      II-like cells), and rat alveolar type II cells to amosite asbestos and assessed
      apoptosis by terminal deoxynucleotidyl transferase-mediated deoxyuridine-5'
      triphosphate-biotin nick end labeling (TUNEL) staining, nuclear morphology,
      annexin V staining, DNA nucleosome formation, and caspase 3 activation. In
      contrast to control medium and TiO2, amosite asbestos and H2O2 each caused AEC
      apoptosis. A role for iron-catalyzed ROS was suggested by the finding that
      asbestos-induced AEC apoptosis and caspase 3 activation were each attenuated by
      either an iron chelator (phytic acid and deferoxamine) or a.OH scavenger
      (dimethyl-thiourea, salicylate, and sodium benzoate) but not by iron-loaded
      phytic acid. To determine whether asbestos causes apoptosis in vivo, rats
      received a single intratracheal instillation of amosite (5 mg) or normal saline
      solution, and apoptosis in epithelial cells in the bronchoalveolar duct regions
      was assessed by TUNEL staining. One week after exposure, amosite asbestos caused
      a 3-fold increase in the percentage of apoptotic cells in the bronchoalveolar
      duct regions as compared with control (control, 2.1% +/- 0.35%; asbestos, 7.61%
      +/- 0.15%; n = 3). However, by 4 weeks the number of apoptotic cells was similar
      to control. We conclude that asbestos-induced pulmonary toxicity may partly be
      caused by apoptosis in the lung epithelium that is mediated by iron-catalyzed ROS
      and caspase 3 activation.

PMID- 11329531
TI  - Significance of arginase and ornithine in malignant tumors of the human skin.
AB  - During neoplastic development, several aspects of the regulation of polyamine
      synthesis undergo profound changes. In extrahepatic mammalian tissues in which
      the urea cycle is not functioning, arginase is believed to supply the cell with
      ornithine, a non-protein amino acid that is a precursor for biosynthesis of
      polyamines. Because the activity of ornithine decarboxylase and polyamine levels
      have been shown to be elevated during carcinogenesis, we decided to investigate
      the role of arginase in the development of malignant tumors of the human skin and
      to examine whether arginase activity and ornithine level can be used as biologic
      markers for distinguishing patients with squamous cell cancer from patients with
      basal cell cancer. For this purpose, we studied tissue arginase activity and
      ornithine level in tumor and adjacent normal tissues in 16 patients (55 +/- 10
      years of age) with malignant skin tumors (8 of which were squamous cell cancers
      and 8 of which were basal cell cancers). The mean arginase activity and ornithine
      levels in tumor tissues (total) were 17.75 +/- 8.54 U/mg protein and 40.89 +/-
      14.88 nmol/mg protein, respectively, versus 3.69 +/- 1.71 U/mg protein and 12.98
      +/- 6.21 nmol/mg protein, respectively, for normal tissues. The mean specific
      arginase activity levels in squamous cell and basal cell cancers of the human
      skin were 18.49 +/- 10.47 U/mg protein and 16.63 +/- 6.00 U/mg protein,
      respectively. The mean ornithine levels in squamous cell and basal cell cancers
      of the human skin were 42.45 +/- 19.10 nmol/mg protein and 39.33 +/- 10.19
      nmol/mg protein, respectively. Our results indicated that (1) arginase activity
      and ornithine levels are elevated in squamous cell and basal cell cancers of the
      human skin; (2) the increased activity of arginase and hence the elevated levels
      of ornithine may be important in the development of malignant tumors of the human
      skin; and (3) although arginase activity and ornithine level may be useful for
      distinguishing patients with malignant skin tumors from healthy subjects, they
      cannot be used as biologic markers for distinguishing patients with squamous cell
      cancer from patients with basal cell cancer.

PMID- 11329532
TI  - Leukocyte activation and leukocyte procoagulant activities after blood contact
      with polystyrene and polyethylene glycol-immobilized polystyrene beads.
AB  - Beads (45 microm) of polystyrene (PS) and polyethylene glycol modified PS
      (TentaGel) with an amino or hydroxyl terminal group were incubated with blood to
      assess the effect of surface area and material chemistry on leukocyte activation.
      After a 2-hour incubation, blood contact with beads activated leukocytes in the
      bulk (tissue factor expression, CD11b up-regulation, and association with
      platelets) independently of material surface chemistry. On the other hand,
      activation of adherent leukocytes was material dependent. After blood contact
      with PS, polyethylene glycol-immobilized PS (PS-PEG) and PS-PEG-NH2 beads, CD11b
      up-regulation in the bulk, platelet-leukocyte aggregates, and leukocyte adhesion
      were all dependent on surface area, whereas tissue factor (TF) expression was
      not. Material-induced leukocyte activation in the bulk was also independent of
      the beads' capacity to activate platelets. However, monocyte adhesion and TF
      expression on beads appeared to be related to the presence of platelets on the
      surface. Material-induced TF expression was able to initiate the extrinsic
      pathway of coagulation, resulting in significant fibrin formation. Although not
      all of our markers of leukocyte activation varied with material area or
      chemistry, it was clear that these materials activated leukocytes in a way that
      resulted in increased procoagulant activity. During blood-material interactions,
      material-induced leukocyte activation may then contribute to thrombogenesis.

PMID- 11329533
TI  - Tetrahydrobiopterin augments arginine transport in rat cardiac myocytes through
      modulation of CAT-2 mRNA.
AB  - Tetrahydrobiopterin (BH4) has been shown to be required for dimerization and
      acquisition of nitric oxide (NO) generating capacity by nitric oxide synthase
      (NOS). In the present study we have investigated the hypothesis that BH4 may
      affect NOS activity through a novel mechanism-namely, modulating arginine
      transport in rat cardiac myocytes. Cardiac myocytes have been previously shown to
      express cationic amino acid transport proteins (y+ system) CAT-1 and CAT-2.
      Increasing extracellular BH4 concentrations up to 0.5 mmol/L augments arginine
      transport in 1 mmol/L arginine media (no BH4, 558 +/- 42 fmol arginine/microg
      protein/min; 0.1 mmol/L BH4, 580 +/- 11 fmol arginine/microg protein/min; 0.5
      mmol/L BH4, 944 +/- 71* fmol arginine/microg protein/min; 1.0 mmol/L BH4, 983+/
      84* fmol arginine/microg protein/min, n = 4; *: P <.05 vs no BH4). Treating the
      cells with lipopolysaccharide (LPS) (10 microg/mL) significantly augmented
      arginine transport only in the presence of BH4 (no BH4, 600 +/- 33 fmol
      arginine/microg protein/min; 0.1 mmol/L BH4, 691 +/- 29*dagger fmol
      arginine/microg protein/min; 0.5 mmol/L BH4, 1123 +/- 32*dagger fmol
      arginine/microg protein/min; 1.0 mmol/L BH4, 1296 +/- 42*dagger fmol
      arginine/microg protein/min, n = 4; *: P <.01 vs no BH4, dagger: P <.05 vs no
      LPS). The administration of biopterin, sodium nitroprusside (NO donor), 2,4
      diamino-6-hydroxy-pyrimidine (inhibitor of BH4 synthesis), and sepiapterin (the
      precursor of de novo synthesis of BH4) to unstimulated cells had no effect on
      arginine uptake values. Using reverse trancriptase-polymerase chain reaction, we
      next studied the steady state levels for CAT-1 and CAT-2 mRNA. Incubation with
      BH4 significantly increased CAT-2 mRNA expression in a concentration-dependent
      manner in 0.1, 0.5, and 1 mmol/L BH4, respectively. Northern blotting analysis
      further confirmed this observation. We also found that in the presence of BH4 in
      these concentrations, CAT-1 mRNA expression was abolished. We suggest that BH4
      augments intracellular arginine availability by modulating CAT-2 mRNA expression
      and suggest that its presence is required for the LPS effect on trans-membrane
      arginine traffic.

PMID- 11329534
TI  - New insights into salivary lactate dehydrogenase of human subjects.
AB  - Lactate dehydrogenase (LDH) is a ubiquitous enzyme that plays a significant role
      in the clinical diagnosis of pathologic processes. The purpose of the current
      study was to examine LDH activity and isoenzyme profile of whole saliva and to
      compare it with the LDH activity of salivary glands and plasma before and after
      exposure to cigarette smoke (CS). The range of LDH activity in whole saliva at
      rest was 360 to 430 U/L. The mean +/- SEM of LDH activity in parotid and
      submandibular/sublingual salivary secretions was 41.3 +/- 19.2 U/L and 77.5 +/-
      30.4 U/L, respectively, which implied that 75% of the whole-saliva LDH originated
      from an extra-salivary gland source. The profile of salivary LDH isoenzymes was
      found to have an entirely different pattern from that found in plasma, similar to
      that found in oral epithelium, indicating that the major source of salivary LDH
      is probably the oral epithelium-shedding cells. Therefore, salivary LDH may be
      evaluated for possible oral mucosal pathologies in a manner similar to that used
      for evaluating other tissue pathologies--such as those in heart, muscle, or liver
      -that can be detected in plasma. Exposure of whole saliva to CS in vitro resulted
      in a 41% reduction in LDH activity. However, CS exposure had no effect on LDH
      activity in plasma. Whole saliva, in contrast to plasma, contains redox-active
      metal ions such as iron and copper that may enhance LDH loss of activity.
      Therefore we conclude that whole saliva in the presence of CS becomes a potent
      protein-modifying agent that can destroy some of its endogenous components.

PMID- 11329535
TI  - An improved method for isolation of unconjugated bilirubin from rat and dog bile.
AB  - Radiolabeled unconjugated bilirubin (UCB) is currently prepared by biosynthetic
      labeling of bilirubin in fistula bile from precursor-labeled delta-aminolevulinic
      acid (ALA) in rats or dogs. With existing methods, yields of labeled UCB from the
      bile are generally less than 50%. We here report modifications of the original
      method of Ostrow et al (Ostrow JD, Hammaker L, Schmid R. The preparation of
      crystalline bilirubin-C(14). J Clin Invest 1961;40:1442-52) that result in
      improvement of yields to 72% from both dog and rat bile. The modifications
      include the initial deproteination of bile with a reverse-phase C18 cartridge,
      removal of ethanol before alkaline hydro-lysis to avoid esterification of UCB,
      and adjustments for the high proportion of non-glucuronide UCB conjugates in dog
      bile not precipitated as lead salts. These improvements should save significantly
      on both costs and animal usage.

PMID- 11329536
TI  - Cardiac services and risk management.

PMID- 11329537
TI  - Volunteers--Our greatest natural resource.

PMID- 11329538
TI  - What's new on the net. Primal medicine.

PMID- 11329539
TI  - Is coronary angioplasty safe in the elderly?
AB  - OBJECTIVE: To evaluate the use of percutaneous transluminal coronary angioplasty
      (PTCA) and the immediate procedural outcomes in the elderly at a tertiary care
      centre. PATIENTS AND METHODS: Between January 1992 and December 1997, a total
      retrospective cohort study of 2322 consecutive patients aged 60 years or older
      underwent PTCA. Patients were categorized into three age groups: group A (60 to
      69 years of age), which included 1294 patients; group B (70 to 79 years), which
      included 895 patients; and group C (80 years of age or older), which included 133
      patients. PTCA was performed using the newest catheter technology as it became
      available. RESULTS: Men comprised 63% of the patients in groups A and B combined,
      and 44% of group C (P<0.001). Canadian Cardiovascular Society angina class IV was
      present in 45% of group C compared with 30% and 35% in groups A and B,
      respectively (P<0.001). The proportion of patients with diabetes mellitus and
      hypertension was similar among the three groups. Acute myocardial infarction
      before PTCA was twice as common at 4.5% (95% CI 3.7% to 5.3%) in group C,
      compared with 2.9% (95% CI 2.7% to 3.1%) and 2.2% (95% CI 2.0% to 2.3%) in groups
      A and B, respectively. The procedural success rate was similar at 93%, 92.7% and
      91.7% in groups A, B and C, respectively. A total of five (0.2%) deaths and eight
      (0.34%) myocardial infarctions occurred in groups A and B combined, while none
      occurred in group C (not significant). More patients in groups A and B underwent
      emergency coronary artery bypass graft than in group C: group A - 22, 3.4% (95%
      CI 3.2% to 3.6%); group B - 16, 3.4% (95% CI 3.2% to 3.6%) and group C - one,
      0.75% (95% CI 0.6% to 0.9%). CONCLUSIONS: In this retrospective series of
      patients, it was shown that PTCA may be performed in the very elderly with high
      procedural success and acceptable risk. Age alone should not be the criterion to
      limit the use of PTCA.

PMID- 11329540
TI  - Results of a routine exercise treadmill testing strategy early after percutaneous
      transluminal coronary angioplasty.
AB  - BACKGROUND: Some physicians use routine exercise treadmill testing early after
      percutaneous transluminal coronary angioplasty (PTCA), yet there have been few
      prospective studies examining the results of such a functional testing strategy.
      OBJECTIVES: To examine the results of a routine post-PTCA exercise treadmill
      testing strategy, and to explore the impact of such a strategy on follow-up
      functional tests and cardiac procedures. PATIENTS AND METHODS: Functional test
      results were examined from a cohort of 226 patients who underwent PTCA at a
      single institution in which a routine functional testing strategy is used. Tests
      were defined as 'routine' if they were performed solely because the patient had a
      prior PTCA. Tests were defined as 'selective' if they were done for a clinical
      indication or if there was no functional testing during the six-month follow-up.
      RESULTS: A total of 183 patients (81%) underwent at least one functional test
      during the six-month period after PTCA. Of these patients, 150 (82%) underwent
      routine functional testing, the majority (73%) of which were exercise treadmill
      tests. Sixty-seven per cent of patients who had routine functional testing had
      their first functional test less than seven weeks after their PTCA. Most routine
      exercise treadmill tests were found to be electrically or clinically
      indeterminate (46%), but a substantial number were either electrically or
      clinically positive (28%), or electrically and clinically negative (39%). Of
      patients who had electrically or clinically positive routine tests, 57% had
      repeat functional testing and 23% had repeat revascularization. Of patients who
      had electrically and clinically negative tests, 53% had repeat functional testing
      and 10% had repeat revascularization. Of the patients who had electrically or
      clinically indeterminate tests, 53% had repeat functional testing and 14% had
      repeat revascularization. The rate of clinical events was less than 4%,
      irrespective of the results of the exercise treadmill tests. CONCLUSIONS: Routine
      exercise treadmill testing early after PTCA is associated with a low clinical
      yield. Most routine exercise treadmill testing results in indeterminate and
      negative tests, which often lead to more functional tests with little difference
      in clinical outcome. These results call into question the use of a routine post
      PTCA functional testing strategy.

PMID- 11329541
TI  - Drop in plasma brain natriuretic peptide levels after successful direct current
      cardioversion in chronic atrial fibrillation.
AB  - BACKGROUND: According to previous reports, plasma atrial natriuretic peptide
      levels increase in atrial fibrillation (AF) and decrease after successful direct
      current (DC) cardioversion, but there have been no reports on plasma brain
      natriuretic peptide (BNP). OBJECTIVE: To determine whether plasma BNP levels
      decrease after successful direct DC cardioversion in patients with chronic AF.
      PATIENTS AND METHODS: Twenty patients who remained in sinus rhythm for at least
      seven days after cardioversion, and 20 normal control subjects, were studied.
      Group A consisted of 10 patients with underlying heart disease, including dilated
      cardiomyopathy (n=2), hypertrophic cardiomyopathy (n=1), mitral valve disease
      (n=3), hypertensive heart disease (n=3) and status after atrial septal closure
      (n=1). Group B consisted of 10 patients with just AF. Group C (serving as
      controls) comprised 20 subjects with normal sinus rhythm and no risk factors.
      RESULTS: Before cardioversion, plasma BNP levels were higher in group A (176.7+/
      128.1 ng/mL) and in group B (96.8+/-51.7 ng/ml) than in group C (6.3+/-3.8 ng/ml)
      (P<0.01 for all). After successful cardioversion, mean plasma BNP levels in
      groups A and B decreased from 136.8+/-105.5 ng/mL to 46.4+/-44.2 ng/mL (P<0.01).
      In group A, plasma BNP levels decreased from 176.7+/-128.1 ng/mL to 62.5+/-54.6
      ng/mL (P<0.01), and in group B, plasma BNP levels decreased from 96.8+/-51.7
      ng/mL to 30.3+/-23.8 ng/mL (P<0.01). CONCLUSIONS: Lone AF raises plasma BNP
      levels, which is more marked if there is underlying structural heart disease
      present, and cardioversion reduces plasma BNP levels. Therefore, high plasma BNP
      levels in patients with chronic AF are likely to be caused by AF and reflect
      cardiac overloading associated with, although contributed to in part by,
      underlying heart diseases.

PMID- 11329542
TI  - Extended donor ischemic times and recipient outcome after orthotopic cardiac
      transplantation.
AB  - BACKGROUND: The effect of extended donor ischemic times on mortality following
      heart transplantation is a matter of considerable debate. PATIENTS AND METHODS: A
      retrospective study of the 261 consecutive heart transplantations performed at
      the centre (University of Alberta, Edmonton, Alberta) between July 1985 and June
      1999 was conducted. Patients were divided into the following two groups based on
      donor ischemic time: 4 h or less and longer than 4 h. Donor and recipient factors
      were analyzed for their effects on 30-day and 90-day survival. RESULTS: Thirty
      day mortality was not significantly greater with prolonged donor ischemic times
      (13%) than with shorter ischemic times (7%, P=0.14). There was also no
      significant increase in 90-day mortality with longer ischemic times (16%) than
      with shorter ischemic times (10%, P=0.27). Actuarial survival (10 years) was
      similar between the groups (P=0.33). Predictors of 30-day and 90-day mortality
      were cardiopulmonary bypass time (P<0.001 and P<0.001, respectively) and lower
      donor weight (P=0.008 and P=0.02, respectively). CONCLUSIONS: Longer donor
      ischemic times were not significantly related to decreased 30-day, 90-day or 10
      year actuarial survival.

PMID- 11329543
TI  - Results following valve replacement for ischemic mitral regurgitation.
AB  - BACKGROUND: Although several authors have favoured mitral repair in ischemic
      mitral regurgitation (IMR), mitral valve replacement is a valuable option and
      most often a necessity in patients with structural IMR. OBJECTIVE: To review the
      authors' experience with valve replacement for patients with acute and chronic
      IMR. The effect of preserving the valve leaflets and the subvalvular apparatus
      during replacement was also evaluated. PATIENTS AND METHODS: The authors'
      experience with mitral valve replacement for IMR between 1990 and 1999 was
      retrospectively analyzed at the Montreal Heart Institute, Montreal, Quebec.
      Results obtained with mitral valve replacement due to degenerative disease were
      used for comparative purposes. RESULTS: Ninety-two patients with IMR and 213
      patients with degenerative mitral regurgitation underwent valve replacement with
      mechanical prostheses (262 of 305 [86%]) or biological prostheses (43 of 305
      [14%]). Fifteen patients (15 of 92 [16%]) died within 30 days of mitral valve
      replacement among IMR patients compared with eight (eight of 213 [4%)] among
      patients with degenerative mitral valve disease (P=0.01). The seven-year survival
      average following mitral valve replacement was 66+/-7% in patients with ischemic
      disease compared with 72+/-4% in patients with degenerative disease (P=0.07).
      Cardiopulmonary bypass time (odds ratio [OR] 1.01) and emergency operation (OR
      2.5) were correlated with the 30-day mortality; the patient's age (OR 1.04) was
      the only risk factor correlated with the seven-year mortality after valve
      replacement. The five-year survival of patients with papillary muscle rupture
      averaged 59+/-12% compared with 78+/-7% in those with functional IMR.
      CONCLUSIONS: Preoperative risk factors and higher early mortality in patients
      with mitral valve replacement for ischemic disease contribute to a lower seven
      year survival than with mitral valve surgery for degenerative disease. The short
      and long term survival of the patients in the acute structural mitral disease
      subgroup was significantly worse.

PMID- 11329544
TI  - Effects of rhythm regularization and rate control in improving left ventricular
      function in atrial fibrillation patients undergoing atrioventricular nodal
      ablation.
AB  - OBJECTIVES: To assess the relative contributions of rate control and rhythm
      regularization to left ventricular function in atrial fibrillation (AF) patients
      undergoing atrioventricular nodal ablation. This was performed by assessing the
      effect of ventricular rhythm regularization on left ventricular function during
      AF, and the effect of varying heart rate on left ventricular function after
      ablation. PATIENTS AND METHODS: Eleven patients with continuous AF and V/VI-R
      pacemakers undergoing therapeutic atrioventricular nodal ablation were studied.
      Preablation patients underwent two 30 min observation periods in a randomized,
      blinded fashion during which they were either in baseline AF (pacer set to
      default V/VI 50/min) or being paced using a rhythm stabilizing algorithm (RSA)
      designed to regularize rhythm without changing baseline ventricular rate. Six
      weeks after ablation, patients were again observed during the two following 30
      min periods: pacing at a low clinically indicated rate (69+/-9 beats/min), and
      pacing at the rapid, mean preablation rate. During all observation periods, left
      ventricular function was measured continuously using a nuclear vest that provided
      validated measures of heart rate, ejection fraction, and normalized end-systolic
      volume (ESV) and end-diastolic (EDV) volume. RESULTS: Before ablation, RSA
      successfully regularized rhythm, decreasing the coefficient of variation of
      interbeat intervals 20+/-5% to 10+/-4% (P<0.001). The heart rate with RSA (105+/
      19 beats/min) was not significantly different from the baseline AF rate (102+/-21
      beats/min). Increased rhythm regularity achieved by RSA significantly improved
      left ventricular function, decreasing ESV from 62+/-12 units to 57+/-11 units
      (P=0.03), and increasing the ejection fraction from 31+/-11% to 36+/-11%
      (P=0.03). After ablation, at the clinically indicated low pacing rate of 69+/-9
      beats/min, a much greater improvement in ejection fraction was observed,
      increasing to 44+/-13% (P=0.005 compared with preablation). However, rapid
      regular pacing at the mean preablation rate of 110+/-18 beats/min eradicated this
      improvement, decreasing the ejection fraction to 31+/-8% (P=0.003), and
      increasing ESV from 53+/-13 units to 62+/-8 units (P=0.006). CONCLUSIONS: Rhythm
      regularity achieved by a regularizing pacing algorithm can significantly, albeit
      modestly, improve left ventricular function in AF. However, more marked
      improvements in left ventricular function seen after ablation are primarily due
      to rate reduction alone.

PMID- 11329545
TI  - Conditioned nutritional deficiencies in the cardiomyopathic hamster heart.
AB  - BACKGROUND: Evidence indicates that nutritional factors may be important in the
      maintenance of myocyte structure and energetics. The failing myocardium has been
      reported to exhibit a depletion of several nutrients that are important for the
      maintenance of intracellular calcium homeostasis and cellular energetics, and
      levels of oxidative stress. This nutrient depletion may contribute to the
      progressive deterioration in myocardial structure and function observed in heart
      failure. OBJECTIVE: To examine the extent to which advanced cardiomyopathy
      results in a depletion of nutrients and/or metabolites and antioxidants, and
      whether supplementation with these nutrients may influence cellular structure or
      function. SUBJECTS AND METHODS: Cardiomyopathic hamsters were randomly placed to
      one of the three following diet groups: chow; control gelled diet; or a
      supplemented gelled diet that provided taurine, carnitine, coenzyme Q10,
      selenium, vitamins E and C, creatine, thiamine and L-cysteine. After
      approximately three months of supplementation, one group of hamsters underwent
      functional testing using a modified Langendorff technique with biopsy samples
      taken for electron microscopy. Myocardial nutrient concentrations were determined
      in a second group of diseased and nondiseased hamsters of the same age. RESULTS:
      Cardiomyopathy resulted in a depletion of vitamin E, creatine, carnitine, taurine
      and coenzyme Q10. Supplementation resulted in improved cardiac ultrastructure,
      function and contractility compared with nonsupplemented hamsters. CONCLUSIONS:
      These studies suggest that heart failure results in 'condition-related nutrient
      deficiencies' that, once corrected, can significantly impact on heart function
      and structure.

PMID- 11329546
TI  - Wolff-Parkinson-White syndrome and isolated left ventricular abnormal
      trabeculation as a manifestation of Leber's hereditary optic neuropathy.
AB  - Myocardial thickening and isolated left ventricular abnormal trabeculation
      (ILVAT) have not been described in patients with Leber's hereditary optic
      neuropathy (LHON) before. Wolff-Parkinson-White syndrome, myocardial thickening
      and ILVAT were found by electrocardiogram, echocardiography and cardiac magnetic
      resonance imaging in a 48-year-old man with bilateral, severely reduced visual
      acuity since age 24 years, palpitations since age 43 years and lower limb muscle
      cramps since age 47 years. Because ILVAT is frequently associated with
      respiratory chain disorders, neurological investigations were initiated,
      revealing the primary LHON mutation G3460A in lymphocytic mitochondrial DNA. On
      the basis of the clinical and genetic data, LHON was diagnosed in the index
      patient, but also in the patient's brother who showed ILVAT as well. Wolff
      Parkinson-White syndrome, myocardial thickening and ILVAT may be rare
      manifestations of LHON.

PMID- 11329547
TI  - Pulmonary valve injury: Swan-Ganz or surgery.
AB  - Pulmonary artery catheter (PAC) is a commonly used monitor in cardiac surgery.
      Pulmonary valve injury from the balloon of the pulmonary artery catheter is
      exceedingly rare; its description by transesophageal echocardiography is
      nonexistent in the literature. A patient is reported who developed a flail
      anterior pulmonary leaflet several days after successful myectomy for
      hypertrophic cardiomyopathy. The temporal sequence of PAC use and four
      transesophageal echocardiography studies over 13 days, with the first three
      showing normal pulmonary valves, suggested pulmonary valve trauma, most likely
      from a Swan-Ganz catheter, as the etiology. Partial damage to the pulmonary valve
      from the original surgery may have predisposed the patient to further damage when
      the PAC was reintroduced in the intensive care unit.

PMID- 11329550
TI  - Canada loses its doyen of cardiology: Robert Earl Beamish MD.

PMID- 11329551
TI  - Musings on time: will we have any left for our patients?

PMID- 11329552
TI  - A computerized system for tracking practice and prescriptive patterns of family
      nurse practitioner students.
AB  - Decisions about the fit between advanced practice nursing curricula and the real
      world of primary care practice should be based on data and not on intuition. The
      purpose of this article is to describe a computerized database system that can be
      used to: 1) track practice (including prescribing) patterns of nurse practitioner
      (NP) students; 2) address data issues that commonly arise; and 3) describe NP
      students' practice during their education to prospective employers. The database
      system uses both the Family Nurse Practitioners Log (FNPLOG), a faculty-developed
      software program, and Epi Info, a companion public domain software program.
      Variables are categorized as being related to sociodemographic, diagnostic, or
      prescriptive components of primary care. The system provides a simple, efficient,
      and feasible way of computerizing, analyzing, and evaluating students' clinical
      experience and practice patterns. The implications for advanced practice nursing
      education will be illustrated along with other potential uses of the database
      system.

PMID- 11329553
TI  - The next step for emergency contraception: over-the-counter availability.
AB  - Emergency contraception to prevent pregnancy after episodes of unprotected sexual
      intercourse has existed since ancient times. Modern medicine began to use
      hormonal methods in the 1960s, and today emergency contraception is used
      regularly in many countries. In the United States, providers do not routinely
      prescribe it, nor do they adequately inform their patients that it is available.
      This occurs even though sufficient information exists on the safety and efficacy
      of this method. Because the effectiveness of emergency contraceptive pills relies
      heavily on prompt administration, better access for patients is essential.
      Recently, proponents of emergency contraception have attempted to better inform
      the public of this resource. In addition, two oral contraceptive products are now
      available and marketed specifically for emergency contraception. The purpose of
      this article is to discuss the safety and efficacy of emergency contraceptive
      pills and the potential for them to become available without a prescription.

PMID- 11329554
TI  - Acute low back pain: diagnostics and treatment.
AB  - How many times have you heard from a patient or groaned yourself "Oh, my aching
      back?" Innocuous movements such as reaching, stooping, or leaning are halted mid
      performance as you sense "something" give, catch, snap, grab, or slide in your
      lower back. Such subjective complaints may also include sensations of discomfort
      described as stabbing, sharp, dull, hot/burning, tingling, or numbing. In
      practice, you will be required to assess these subjective symptoms, effectively
      document objective data, formulate a diagnosis, and plan appropriate treatment
      for your patients. Careful attention to history, associated symptoms, and
      following a systematic approach to back pain can make the rule-in/out
      differentials less taxing on both the practitioner and the patient.

PMID- 11329555
TI  - Superior vena cava syndrome.
AB  - Superior vena cava syndrome (SVCS) is a relatively common occurrence in the
      oncology patient. Nurse practitioners should keep a high index of suspicion for
      the development of this condition. Early detection of signs and symptoms can lead
      to a more favorable patient response. Diagnostics and referral to an oncologist
      should be initiated immediately. Biopsy of a suspected lesion is now the standard
      of care. The standard of treatment remains localized radiation therapy and
      chemotherapy as appropriate. SVCS may be an oncological emergency, and it may be
      the presenting symptom of a malignancy. Identification of this potentially fatal
      circumstance may greatly improve the patient's outcome.

PMID- 11329556
TI  - Creating order out of chaos: models of GNP practice with hospitalized older
      adults.
AB  - It has been well documented that hospitalization of an older adult can trigger a
      cascade of events that negatively affect quality of life long after
      hospitalization. Three models of care directed by hospital-based geriatric nurse
      practitioners (GNPs) are described. The GNPs' roles include primary care
      provider, consultant, educator, researcher, and/or administrator. In one model,
      the GNP collaborated with a multi-disciplinary team to create a clinical pathway,
      the Functional Recovery Pathway. In the second model, the GNP and nurse manager
      addressed the issue of fall risk with an education program for the staff. As a
      result, the fall rate decreased 5.8%. In a third model, the GNP coordinated care
      of hospitalized nursing home residents in a "scatter bed" program. Working
      synergistically with a case management program, the length of stay for this group
      of patients decreased from a median of 12 days to 9 days in the first year to 6.8
      days in the third year. All three models showed that the GNP facilitate change,
      improve resource utilization, and create innovative strategies to optimize care
      for hospitalized elders.

PMID- 11329557
TI  - Comparison of past and current barriers to novice nurse practitioner practice:
      The California perspective.
AB  - Novice nurse practitioners (NPs) face unique obstacles to practice. Few studies
      examine factors influencing early NP clinical performance. Therefore, this
      research project was designed to collect data from members of an NP professional
      organization who were asked to identify barriers encountered within the first 3
      years of practice. Responses were received from 243 beginning and more
      experienced NPs. The top three barriers named were lack of public knowledge, lack
      of positions for NPs, and a lower salary than anticipated. The promotion of NP
      assets through expanded media coverage and individual educational efforts, the
      national standardization of the role, and the elimination of restrictive practice
      legislation can help reduce current barriers. Through the efforts of individuals,
      NP professional groups, and legislators, existing practice constraints can be
      mitigated, potential barriers anticipated, and solutions generated to ensure the
      continued success of this essential advanced practice role.

PMID- 11329558
TI  - Breast cancer screening education: comparing outcome skills of nurse practitioner
      students and medical residents.
AB  - BACKGROUND: Nurse practitioner students, along with all primary care trainees,
      need breast cancer screening education. The purpose of the study was to compare
      the performances of nurse practitioner students and medical residents before and
      after receiving training. METHODS AND RESULTS: In a pretest/posttest design, 51
      nurse practitioner students and 47 medical residents received training either
      from a standardized patient or from a lecture/demonstration class. Before
      training and 1 year after, participants took the written test and had their
      skills evaluated by a standardized patient. There were no significant differences
      between the nurse practitioner students and the medical residents in the mean
      scores on the written pretest or on the written posttest with both groups
      improving their scores. The nurse practitioner students had significantly higher
      scores on the practicum posttest (P <.05). CONCLUSIONS: Nurse practitioner
      students perform well in learning breast cancer screening. More than one method
      of teaching is effective.

PMID- 11329559
TI  - Nurse practitioners enter the new millennium: a global initiative.
AB  - Health care for all was the theme as nurse practitioners gathered in the United
      States for the 8th International Conference. At the conference, nurse
      practitioners representing 27 countries discussed issues of global concern. Nurse
      practitioners face common challenges in their global community. Strategies for
      practice and forward movement of the advanced role are discussed. Universal
      challenges include titling, legal recognition, legal status, prescriptive
      authority, and reimbursement. These issues continue to be addressed as we move
      toward a global community.

PMID- 11329560
TI  - Factors that facilitate or hinder mentoring in the nurse practitioner
      preceptor/student relationship.
AB  - Mentoring, a process thought to be crucial for the novice nurse practitioner
      during the time of transition to advanced practice, has implications for role
      socialization and, ultimately, for patient care outcomes. In-depth interviews of
      mentored or non-mentored nurse practitioner students, drawn from an earlier phase
      of the present study (Hayes, 1998) and identified as outliers, provided a basis
      for exploring the meaning of factors that may facilitate or hinder mentoring in
      the NP preceptor/student relationship. Study findings confirmed and illuminated
      earlier results (Hayes, 1998) predictive of mentoring, such as time in the
      practicum, preceptor experience, and choice of preceptor rather than acceptance
      of faculty assignment. However, NP preceptor/student age differences, student
      nursing experience, and the tone of the clinical setting can either facilitate or
      hinder the development of mentoring. Although gender and discipline of the
      preceptor may be important to many students, a humanistic precepting style may be
      equally or more important. Understanding factors that facilitate or hinder
      mentoring will help faculty to better plan clinical experiences, assist
      preceptors in their potential roles as mentors, and maximize learning
      opportunities for mentor-seeking students who must navigate successfully in
      today's cost-conscious, quality outcome-oriented health care environment.

PMID- 11329561
TI  - Using the National Library of Medicine's PubMed to improve clinical practice.

PMID- 11329564
TI  - Esophagogastric dissociation versus fundoplication: Which is best for severely
      neurologically impaired children?
AB  - PURPOSE: Neurologically impaired children (NIC) often have swallowing
      difficulties, severe gastroesophageal reflux, recurrent respiratory infections,
      and malnutrition. Bianchi proposed esophagogastric dissociation (EGD) as an
      alternative to fundoplication and gastrostomy. The authors compared these 2
      approaches. METHODS: Twenty-nine consecutive symptomatic NIC refractory to
      medical therapy were enrolled in a prospective study and divided into 2 groups: A
      (n = 12), NIC who underwent fundoplication and gastrostomy; B (n = 14), NIC who
      underwent EGD. Three were excluded because of previous fundoplication.
      Anthropometric (percentage of the 50th percentile/age of healthy children) and
      biochemical parameters, respiratory infections per year, hospitalization (days
      per year), feeding time (minutes), and "quality of life" (parental psychological
      questionnaire, range 0 to 60), were analyzed (t test and Mann-Whitney test)
      preoperatively and 1 year postoperatively. Complications were recorded. RESULTS:
      Compared with group A, group B presented a statistically significant increase of
      all anthropometric and nearly all biochemical parameters with a statistical
      difference in terms of respiratory infections, hospital stay, feeding time, and
      psychological questionnaire. In group A, 2 bowel obstructions, 1 tight
      fundoplication, 1 dumping syndrome, and 3 failures of fundoplication occurred.
      Group B presented 1 anastomotic stricture, 1 paraesophageal hernia, and 1 bowel
      obstruction. CONCLUSIONS: Compared with fundoplication and gastrostomy, EGD
      offered better nutritional rehabilitation, reduction in respiratory infections,
      and improved quality of life. EGD can be rightfully chosen as a primary
      procedure.

PMID- 11329565
TI  - Early referral is essential for successful pediatric small bowel transplantation:
      The Canadian experience.
AB  - PURPOSE: The mortality rate for pediatric patients on the waiting list for
      transplantation has a major impact on the overall effectiveness of pediatric
      small bowel transplantation. This review was undertaken to determine the fate of
      Canadian children assessed for small bowel transplant and the outcome of those
      who undergo transplant in the tacrolimus era. METHODS: The authors reviewed
      retrospectively all of the pediatric small bowel patients listed since 1988
      through the Canadian Organ Replacement Register and all the children referred to
      our program in its first year. All children who received a small bowel transplant
      between January 1993 and December 1999 also were reviewed. RESULTS: The mortality
      rate for pediatric patients on the small bowel transplant list was 53% after an
      average of 105 days on the list compared with 212 days for those who underwent
      transplant. Patients who died while on the list were younger and had signs of
      advanced liver disease at the time of listing. Thirteen Canadian children have
      received a small bowel transplant with an overall 1-year patient and graft
      survival rate of 61% and 53%, respectively. Survivors are all independent from
      total parenteral nutrition. CONCLUSION: Many Canadian children miss their
      opportunity for a successful small bowel transplant because of late referrals and
      a shortage of donor organs.

PMID- 11329566
TI  - Pediatric trauma registries: the foundation of quality care.
AB  - BACKGROUND/PURPOSE: Traumatic injuries cause substantial morbidity and mortality
      in children. Trauma registries are essential to assess and improve standards of
      trauma care. An interprovincial study of pediatric trauma between 6 centers
      across Canada who use identical software components was completed. METHODS: Data
      were collected from April 1, 1995 to December 31, 1998 for children aged 1 day to
      17 years with an injury severity score of > or = 12. Cause of injury, injury time
      and day, gender, age, injury scores, length of hospital stay, and outcomes were
      compared. RESULTS: A total of 1,276 patients were included. Mean age was 10.3 +/-
      5.6 years. Motor vehicle collisions were the most common mechanism of injury
      (56%). Boys were more often injured (66%; P < .05). Injuries occurred mainly
      between 1600 and 2400 hours (P < .0001). Mean hospital stay was 11.5 +/- 16.6
      days. The longest stays in the hospital were among those who had an abdominal
      abbreviated injury score (AIS) of 1 (P < or = .03). Patients with similar injury
      severities remained twice as long in Winnipeg Children's Hospital (hospital 5),
      hospital 2, and hospital 6 as compared with patients in hospital 3 (P < .05).
      Differences existed in discharge placement between hospitals (P < .0001).
      CONCLUSIONS: This study was the first to compare pediatric patients in multiple
      Canadian centers using identical trauma registries. Variations in length of stay
      and discharge placements between hospitals were identified. Further analysis of
      data in the registries may clarify these differences and serve as a foundation
      for hospitals to improve the quality of patient care.

PMID- 11329567
TI  - Endosurgery and the senior pediatric surgeon.
AB  - BACKGROUND: Endosurgery is difficult for the senior pediatric surgeon to master
      because the technique has a steep learning curve, lacks tactile sense, uses
      elongated instruments, and is ergonomically tiring. METHODS: The senior author,
      starting at age 53, has performed more than 300 endoscopic procedures at both
      children and community hospitals. A full year was required to master laparoscopic
      Nissen fundoplications. Conversion to open procedures from bleeding and
      enterotomies were committed in the first year of endosurgery. Facility with
      endosurgery is gained by performing common and frequent procedures as
      appendectomies. CONCLUSION: The advantages of endosurgery in pain control and
      shortened hospitalization make the technique deserving of commitment by the
      senior pediatric surgeon.

PMID- 11329568
TI  - Surgery for ovarian masses in infants, children, and adolescents: 102 consecutive
      patients treated in a 15-year period.
AB  - BACKGROUND/PURPOSE: Ovarian pathology, although rare in children, must be
      included in the differential diagnosis of all girls who present with abdominal
      pain, an abdominal mass, or precocious puberty. METHODS: To improve clinical
      appreciation of these lesions, the authors reviewed the presentation, evaluation,
      and outcome of all patients with ovarian pathology surgically treated at their
      institution since 1985. RESULTS: One hundred two girls (aged 9.8 +/- 5.5 years;
      range, 2 days to 20 years) underwent 106 separate ovarian operations (43 salpingo
      oophorectomies, 21 oophorectomies, 33 ovarian cystectomies, and 9 ovarian
      biopsies). Of those presenting with acute abdominal pain (n = 59), 25 (42%) had
      ovarian torsion (14 associated with a mature teratoma), and only 1 (2%) had a
      malignant tumor. In contrast, of those presenting with an abdominal mass (n =
      23), 6 (26%) had malignancies. There was no age difference between those with
      benign disease (9.9 +/- 5.6 years; n = 96) and those with malignant tumors (8.6
      +/- 3.9 years, n = 10). Nine children had 10 operations for presumed malignant
      tumors (3 dysgerminomas, 2 immature teratomas with foci of yolk sac tumor, 2
      juvenile granulosa cell tumors, 1 yolk sac tumor, and 1 Sertoli-Leydig cell
      tumor). These patients all had unilateral salpingo-oophorectomy, 4 had
      chemotherapy, and all are now disease free at 8.4 +/- 4.1 years follow-up.
      CONCLUSION: Ovarian pathology remains a rare indication for surgery in girls less
      than 20 years of age. Because most of these lesions are benign, ovarian
      preserving operations should be performed whenever feasible.

PMID- 11329569
TI  - Altered nitric oxide production in the premature gut may increase susceptibility
      to intestinal damage in necrotizing enterocolitis.
AB  - BACKGROUND/PURPOSE: Nitric oxide (NO) mediates enteric smooth muscle relaxation
      and mucosal protection. The authors have identified an ontogenically determined
      pattern of enteric NO neural maturation that may render the distal gut of
      premature piglets susceptible to injury. METHODS: NO synthase (cNOS and iNOS)
      activities were measured in the developing piglet gut wall and compared with gut
      from an intraluminal model of necrotizing enterocolitis (NEC) at different times.
      RESULTS: In premature animals, iNOS activity was significantly higher 3 hours
      after NEC induction compared with similarly treated 3-day-old piglets. INOS
      levels continued to rise 6 hours after NEC induction in prematures. Premature
      animals (labor induced by prostaglandins) failed to show such a rise in iNOS. In
      3 day olds, iNOS levels increased significantly 16 hours after injury compared
      with the 3-hour group. CONCLUSIONS: iNOS production increases in premature
      piglets with NEC compared with full-term NEC animals and continues to rise in the
      presence of intestinal damage regardless of developmental status. Maternal
      administration of prostaglandins attenuates this rise in iNOS activity. Elevated
      NO production in premature gut may contribute to increased susceptibility to
      damage in NEC.

PMID- 11329570
TI  - Training general surgery residents in pediatric surgery: A Canadian survey.
AB  - BACKGROUND/PURPOSE: The training of general surgeons in pediatric surgery is an
      important educational role of pediatric surgeons (PS). The authored surveyed this
      training process and the related expectations and perceptions of competence.
      METHODS: The authors surveyed all practicing members of the Canadian Association
      of Paediatric Surgeons (CAPS) in Canada, all general surgery program directors
      (PD), and all final year general surgery residents (GS). Questions included
      exposure to pediatric surgery, expected and perceived competence in managing
      common pediatric general surgical problems, and trainee practice intentions.
      RESULTS: Response rate to date was 51% from PS, 69% from PD, and 19% from GS.
      Sixty-seven percent of PS considered the exposure to pediatric surgery
      satisfactory, yet only 1 of 7 residents planning on pursuing general surgery felt
      adequately prepared. Trainees were expected to be competent in the conditions
      polled by 65% of PS and 74% of PD, yet only 38% of the trainees actually felt
      competent in them. The largest discrepancies were found for infant hernia,
      newborn colostomy, and cryptorchidism. Presence of a fellowship program and size
      of training program had no impact on perceived competence. CONCLUSIONS: Training
      of general surgeons in pediatric surgery varies across Canadian programs.
      Perceived resident competence often lags behind program and faculty expectations.
      These data can be used for directing educational priorities in general surgery
      programs.

PMID- 11329571
TI  - Combined posterior sagittal and three-flap anoplasty in the repair of anorectal
      anomalies.
AB  - PURPOSE: The aim of this study was to describe a new technique for the repair of
      high and intermediate imperforate anus. METHODS: From 1989 to 1999, 22 children
      with high and intermediate imperforate anus (17 boys, 5 girls) were operated on
      with a combination of a posterior sagittal and 3-flap perineal anoplasty. Long
      term clinical follow up (to a maximum of 10 years) was done in all patients as
      well as a recent phone interview with a questionnaire regarding bowel function
      and degree of satisfaction with the result of the surgical correction. A
      continence ratio (CR, patient score/maximum possible score) was obtained by a
      blinded interviewer. RESULTS: A continence survey was obtained in 19 patients.
      The average CR was 0.68. The CR for high anomalies was 0.62 and for intermediate
      anomalies was 0.78 (0.84 for girls and 0.64 for boys). Patients with sacral
      anomalies had a CR of 0.58. Two patients with Trisomy 21 had associated
      Hirschsprung's disease and were excluded from analysis. CONCLUSIONS: Advantages
      of this combined surgical approach are excellent anatomic exposure, the ability
      to limit rectal mobilization to a minimum, reduction of the incidence of mucosal
      prolapse, the new skin-lined anal canal may assist attainment of continence by
      providing a "sensory warning zone," and, finally, the cosmetic appearance is
      satisfactory.

PMID- 11329572
TI  - Laparoscopic surgery for gastroesophageal reflux disease during the first year of
      life.
AB  - BACKGROUND: Very few children need gastroesophageal antireflux surgery during
      their first year of life; hence, no series has been published so far. The authors
      report their experience in 3 centers. METHODS: From January 1993 to December
      1998, 36 infants between 23 days and 13 months of age, suffering from
      gastroesophageal reflux disease (GERD), underwent surgery by a laparoscopic
      approach. The patients' weights ranged from 2.4 to 8.5 kg. Preoperative
      diagnostic studies included esophagograms, manometries, endoscopies, and pH
      metries. Fifteen babies (41.6%) had associated anomalies, and 10 (27.7%) were
      neurologically impaired. Thirty-six laparoscopic fundoplications were performed
      according to either Toupet's procedure (17 of 36), Rossetti's (10 of 36),
      Nissen's (8 of 36) or Lortat-Jacob's (1 of 36). Four infants previously had
      undergone a gastrostomy, whereas 6 needed one during the antireflux procedure.
      RESULTS: There was no mortality in our series. Three infants (8.3%) had an
      intraoperative complication: 1 lesion of a diaphragmatic vessel, 1 pneumothorax,
      and 1 case of severe hiatal hernia requiring conversion to open surgery. During
      the median follow-up of 22 months, 4 redo procedures were performed (11.1%).
      CONCLUSIONS: This experience shows the feasibility of laparoscopic fundoplication
      even in children below 1 year of age. An accurate preoperative diagnostic study
      is mandatory, because 50% of these patients presented associated anomalies. A
      long and accurate follow-up is necessary to evaluate long-term results and detect
      possible complications, which can occur as late as 1 year after surgery. In
      addition, we believe that redo antireflux surgery is possible by the laparoscopic
      approach without major difficulties, based on our larger experience with older
      children.

PMID- 11329573
TI  - Acute chest syndrome after abdominal surgery in children with sickle cell
      disease: Is a laparoscopic approach better?
AB  - BACKGROUND/PURPOSE: Acute chest syndrome (ACS) is the leading cause of
      hospitalization and death among patients with sickle cell disease (SCD). Surgery
      is a risk factor for the development of ACS. It has been suggested that
      laparoscopic surgery could diminish the risk of sickle-related complications;
      therefore, more procedures may be encouraged in asymptomatic patients. The goal
      of the authors was to determine the incidence of postoperative ACS and assess for
      predisposing factors in all sickle cell patients undergoing abdominal surgery.
      METHODS: A retrospective analysis of all sickle cell patients receiving abdominal
      surgery (open and laparoscopic) between 1994 and 1998 was conducted. Data
      pertaining to demographics, perioperative clinical status, postoperative care,
      and outcome were collected and analyzed using Student's t test or chi(2) where
      appropriate. RESULTS: Fifty-four children underwent 62 procedures (35 abdominal
      and 27 extracavitary). All abdominal cases were either cholecystectomy or
      splenectomy (22 laparoscopic and 13 open). ACS occurred in 7 of 62 (11.3%)
      overall, and all were in abdominal cases 7 of 35 (20%). ACS occurred in 5 of 22
      (22.7%) laparoscopic cases and 2 of 13 (15.4%) open cases. Operating time was
      significantly longer in the laparoscopic group compared with open cases (P <.05).
      A higher percentage of patients who had ACS had at least 1 previous episode
      (71.4% v 39.3%; P value not significant) and a smaller percentage of ACS patients
      received a preoperative blood transfusion (14.3% v 32.1%; P value not
      significant). Postoperative hospitalization was prolonged if ACS occurred (9 +/-
      2 v 3 +/- 2 days; P <.05). CONCLUSIONS: Abdominal surgery carries a significantly
      high risk (20%) of ACS. Laparoscopy does not decrease the incidence of ACS
      compared with open approach. Predisposing factors were not significant in
      predicting postoperative ACS. There is considerable morbidity and potential cost
      implications in patients with ACS.

PMID- 11329574
TI  - Directed blood donation in pediatric general surgery: Is it worth it?
AB  - PURPOSE: To date, there are no data to support the safety, efficacy, and cost
      benefit ratio of donor-directed blood donation (DD). The objectives were to
      determine whether a DD program in pediatric general surgery practice is
      justified. METHODS: A retrospective analysis was conducted of the transfusion
      practice and all DD requests received by transfusion services in a full calendar
      year (1997) at a tertiary care pediatric hospital. The authors examined the
      donations, utilization, and possible benefits for the recipients. RESULTS: A
      total of 22,527 units of blood were transfused in 1997. General surgery used 471
      (2%) of the total and 471 of 4,825 (10%) of all surgical transfusions. Total DD
      requests were 219 with only 11 of 219 (5%) originating from the general surgery
      department. After all the exclusions, 133 of 219 (61%) requests had DD blood
      available. DD blood had a higher true-positive rate for transmissible disease
      (1.1% v 0.10%), high-risk activity (2.5% v 1.2%), and malaria risk (3.1% v
      0.31%). Total utilization of DD blood was 132 of 236 units (55.9%) and general
      surgery utilized 4 of 11 (36.4%) of their directed donations. Thirty-seven
      patients (27.8%) benefited from decreased donor exposure. No general surgery
      patient received more than 1 blood component to benefit from decreased donor
      exposure. CONCLUSIONS: DD deferral rates are higher than for volunteer donors for
      infectious disease markers, malaria, and high-risk activities. There is no
      evidence that DD is safer than volunteer donation. DD blood wastage of 63.6% is
      much higher than in volunteer donation (7%). Thirty-seven patients (28%) received
      multiple units from one donor suggesting a benefit from decreased donor exposure.
      Given the low frequency of transfusion and the poor utilization of DD in general
      surgical practice, a DD program is not justified.

PMID- 11329575
TI  - Farm accidents in children: eleven years of experience.
AB  - BACKGROUND/PURPOSE: The aim of this study was to review accidental injuries to
      children on farms. METHODS: Between January 1988 and December 1999, childhood
      farm injuries referred to a trauma center were reviewed. RESULTS: Forty-five
      children under 19 years of age were identified. Mean age was 7.3 years. Male to
      female ratio was 2:1. A total of 31 of 45 (69%) survived. A total of 14 of 45
      (31%) died. The mechanism of injury was tractor in 15 (33%), animals in 13 (29%),
      other machinery in 9 (20%), falls in 4 (9%), burns in 2 (4%), equipment in 1
      (2%), and mechanism not documented in 1 (2%). Twelve deaths involved tractors or
      machinery (86%), and 2 involved animals (14%). Thirty of forty-five (67%)
      accidents occurred between June and October. A total of 28 of 45 (62%) occurred
      between 1 PM and 6 PM. Nine fatalities (64%) were supervised. Predominant
      injuries were orthopedic in 25 of 45 (56%), neurologic in 19 of 45 (42%), and
      thoracoabdominal in 10 of 45 (22%). Eighteen (40%) underwent orthopedic surgery.
      Six patients (13%) had long-term disability. Seven survivors and 7 fatally
      injured patients (31%) had multiple injuries. Seven of 14 fatalities (50%) had
      solitary head injuries. The average transport time from scene to rural hospital
      was 1.5 hours, from rural hospital to trauma center, 2.3 hours. Twelve of
      fourteen fatalities (86%) were declared dead at the scene, and 2 died en route.
      CONCLUSION: Efforts must be focused to prevent tractor and animal injuries.

PMID- 11329576
TI  - Primary peritoneal drainage for increasing ventilatory requirements in critically
      ill neonates with necrotizing enterocolitis.
AB  - BACKGROUND/PURPOSE: Primary peritoneal drainage (PPD) is an established therapy
      for premature neonates with necrotizing enterocolitis (NEC) and free
      intraperitoneal air. This study seeks to evaluate the efficacy of PPD in ill
      premature neonates with severe abdominal distension and increasing ventilatory
      requirements without free intraperitoneal air. METHODS: Eleven neonates
      (gestational age, 27 +/- 0.59 weeks; age, 25 +/- 4.3 days; birth weight, 862 +/-
      67 g) with NEC underwent bedside PPD under local anesthesia for rapid clinical
      deterioration characterized by severe abdominal distension and increasing
      ventilatory requirements. None showed radiographic evidence of free
      intraperitoneal air. Mean airway pressure (MAP) and oxygenation-index (OI) were
      analyzed 24 hours before, immediately before and 24 hours after surgery. The
      patients were followed up to discharge from hospital. Statistical analyses were
      performed using analysis of variance (ANOVA) for repeated measures. RESULTS: Mean
      airway pressure (MAP) showed a significant difference (P <.05) increasing from
      7.1 +/- 0.75 cm H2O 24 hours before surgery to 11 +/- 1.3 cm H2O immediately
      before surgery and decreasing to 9.9 +/- 1.1 cm H2O 24 hours after drainage.
      Likewise, OI measured at the same time intervals showed significant differences
      (P <.05) deteriorating from 5 +/- 1.2 to 26 +/- 6.9 then improving to 13 +/- 3.5.
      A significant quadratic effect (P <.03) was evident for MAP and OI (ie, values
      significantly rose then fell). There were six 30-day survivors (55%), and 3
      survived to discharge (27%). Of the long-term survivors, 2 required operative
      fistula closure, and 1 needed no further surgery. CONCLUSION: Bedside PPD for
      increasing ventilatory requirements and abdominal distension in critically ill
      neonates with nonperforated NEC is a simple technique that offers rapid
      stabilization, although ultimate mortality rate remains high.

PMID- 11329577
TI  - Endoscopic retrograde cholangiopancreatography in children: A surgeon's
      perspective.
AB  - PURPOSE: The aim of this study was to review the indications, success rate, and
      complications of endoscopic retrograde cholangiopancreatography (ERCP) in the
      pediatric age group. METHODS: From 1990 to 1999, 21 ERCP procedures were
      attempted in 20 patients. They consisted of 8 boys and 12 girls whose age ranged
      from 4 to 17 years (mean, 11.3 years). Fourteen were performed under deep
      sedation (mean age, 12.8 years), and 7 were done under general anesthesia (mean
      age, 7.6 years). All ERCP procedures were performed by experienced adult
      endoscopists. RESULTS: The indication for ERCP was biliary in 15 patients. Eleven
      had suspected choledocholithiasis by either ultrasound scan, intraoperative
      cholangiogram or magnetic resonance imaging (MRI). In 6 cases, the ERCP was done
      for pancreatic pathology. In 11 patients, the ERCP was diagnostic only, and in 10
      a therapeutic procedure was done. The overall success rate was 90.5%. Post-ERCP
      complications consisted of 6 episodes of pancreatitis (28.5%), 4 of which
      followed a therapeutic procedure, and 1 episode of bleeding. Pancreatitis
      resolved 2 to 6 days post-ERCP. The patients underwent follow-up between 2 and 56
      months after the ERCP (mean, 11 months). CONCLUSIONS: The authors conclude that
      even in experienced hands, ERCP in the pediatric population has a much higher
      complication rate than in adults (33.3%). We recommend that very specific
      indications be met before subjecting a pediatric patient to an endoscopic
      retrograde cholangiopancreatography.

PMID- 11329578
TI  - Internal anal sphincter achalasia: outcome after internal sphincter myectomy.
AB  - BACKGROUND: Internal anal sphincter achalasia (IASA), also referred to as
      ultrashort segment Hirschsprung's disease (HD), is a clinical condition with
      presentation similar to HD, but with the presence of ganglion cells on rectal
      biopsy. The diagnosis of IASA is made on anorectal manometry, which shows the
      absence of rectosphincteric reflex on rectal balloon inflation. Altered
      intramuscular innervation has been reported in IASA. The purpose of this study
      was to review the outcome after internal sphincter myectomy in patients with
      IASA. METHODS: Fifteen consecutive patients (age range, 2 years to 12 years) with
      IASA underwent posterior internal sphincter myectomy. All patients presented with
      severe constipation with or without soiling. The diagnosis of IASA was made by
      anorectal manometry. HD was excluded in these cases by the presence of ganglion
      cells and normal acetylcholinesterase activity on suction rectal biopsies.
      Internal sphincter (IS) specimens were examined using immunohistochemistry for
      the general neuronal marker PGP 9.5 and synapsin 1 (a presynaptic marker) and
      using general histochemistry for NADPH-diaphorase. All patients underwent follow
      up for periods from 2 years to 6 years. RESULTS: PGP 9.5, synapsin 1 and NADPH
      diaphorase positive nerve fibers were either absent or markedly reduced in IASA
      specimens compared with controls, confirming previous reports of defective
      intramuscular innervation in IASA. At the time of follow-up, 7 patients have
      regular bowel motions and are not on any laxatives. Six patients have normal
      bowel habits but are on small doses of laxatives. One patient is able to stay
      clean with regular enema regimen. One patient required resection of dilated and
      redundant sigmoid colon and now has normal bowel habits with laxatives.
      CONCLUSION: The majority of patients with internal anal sphincter achalasia can
      be treated successfully by internal sphincter myectomy.

PMID- 11329579
TI  - Pulmonary structural maturation and pulmonary artery remodeling after reversible
      fetal ovine tracheal occlusion in diaphragmatic hernia.
AB  - PURPOSE: Congenital diaphragmatic hernia (CDH) is associated with thickened
      pulmonary arteries (PA) contributing to pulmonary hypertension. In the current
      study, the effects of antenatal glucocorticoids and reversible tracheal occlusion
      (TO) on PA structure were assessed in a hypoplastic lung model. METHODS: A left
      sided CDH was created in fetal lambs at 80 days gestation, TO at 108 days, and
      release of the occlusion (TR) at 129 days. All were given 1 dose of maternal
      glucocorticoids at 135 days. At 136 days (term, 145 days), the fetus was
      delivered by cesarian section. CDH (n = 7), CDH + TO (n = 6), CDH + TO + TR (n =
      6), and unoperated twin controls (n = 16) were compared. Outcome measurements
      were (1) lung growth, represented by lung weight to body weight ratio (LW/BW),
      (2) lung structural maturation, which is inversely proportional to mean terminal
      bronchiole density (MTBD), (3) PA medial and adventitial areas (square
      micrometers), (4) lung capillary load, which is the ratio of vessel surface area
      (SA) to tissue SA ratio. RESULTS: CDH lungs were hypoplastic with a low LW/BW and
      high MTBD. The small PAs (<75 microm) of CDH had an increased medial area,
      indicating increased muscle mass and an increased adventitial area. CDH + TO +/-
      TR increased LW/BW and achieved normal structural lung maturity with a low MTBD.
      Only CDH + TO thinned the PA medial area closer to control values. The
      adventitial area remained thick in CDH +/- TO +/- TR when compared with controls.
      All 4 groups had similar capillary load. CONCLUSIONS: TO may be especially
      important for PA remodeling in the latter part of gestation, because TR 1 week
      before delivery prevents thinning of the small PAs in CDH. The shaping achieved
      by TO in terms of lung growth, structural maturity, and pulmonary artery medial
      area thinning may prove beneficial in lessening the severity of the associated
      pulmonary hypertension in CDH.

PMID- 11329580
TI  - In vivo measurement of intestinal absorption using 3-0 methylglucose in short
      bowel syndrome.
AB  - PURPOSE: The management of patients with short bowel syndrome is complicated by
      the paucity of methods to assess in vivo the absorptive capacity of the remaining
      bowel. The purpose of this experiment was to assess the feasibility of using
      urinary recovery of 3-0 methylglucose (3-0 MG) as a quantitative measure of
      carbohydrate absorptive capacity, comparing it with in vivo absorption and in
      vitro glucose transport studies. METHODS: Male Sprague Dawley rats underwent
      either a 90% proximal small bowel resection or sham resection (n = 8 in each
      group). Animals were pair fed, weighed, and followed up for 14 days. A 3-day
      balance study was done, measuring feed intake and fecal output for percentages of
      fat and energy absorption. Animals were gavaged with 3-0 MG/Mannitol solution,
      and 4-hour urinary recovery of sugars was assessed using high-performance liquid
      chromatography (HPLC). On different days these studies were repeated with
      increasing amounts of added normal glucose (1 mol/L, 1.25 mol/L, and 1.5 mol/L)
      in the gavage solution given to compete for 3-0 MG transport, and thus increase
      the "sensitivity" of the test. Animals were then killed, and sections of
      intestine taken for in vitro assessment of glucose transport using radiolabeled 3
      0 MG in Ussing chambers. RESULTS: Total energy, carbohydrate, and fat absorption
      all were reduced significantly in the resected animals, as was 3-0 MG urinary
      recovery (62.9 +/- 10.5%) in controls versus (35.8 +/- 17.5%) in resected animals
      (P <.05). 3-0 MG urinary recovery correlated well with dietary carbohydrate
      absorption (r = 0.74), and with Ussing chamber measures of glucose flux (r =
      0.97). Adding exogenous glucose to the test solution to "compete" for 3-0 MG
      transport sites did not improve sensitivity. CONCLUSIONS: These results show that
      3-0 MG is useful in measuring nutrient absorption capacity in rats after massive
      small bowel resection. Further studies to validate these methods in human
      patients with short bowel syndrome are suggested.

PMID- 11329581
TI  - Systemic GLP-2 levels do not limit adaptation after distal intestinal resection.
AB  - BACKGROUND/PURPOSE: Glucagonlike peptide 2 (GLP-2) is trophic for the small
      bowel; it is produced by L cells in the distal intestine in response to luminal
      nutrients. This study tests the hypothesis that distal small bowel and cecal
      resection would decrease GLP-2 levels and reduce adaptation. METHODS: Male
      Sprague-Dawley rats (200 to 300 g) underwent either ileal transection (controls)
      or resection of the ileum and cecum, leaving 10 or 20 cm jejunal remnant
      anastomosed to the ascending colon. Animals were followed up for up to 21 days.
      Endpoints were daily weights, intestinal histology, in vivo absorption of 3-0
      methylglucose (a measurement of active nutrient absorptive capacity), and serum
      GLP-2 levels. RESULTS: The control group had a maximum 6% weight loss around day
      2, and then recovered with a steady weight gain. The 10-cm jejunal remnant group
      lost weight continuously and never recovered postsurgery. The 20-cm jejunal
      remnant group of animals had a maximum of 12% weight loss by day 4 and then
      slowly gained weight. The average villus height increased significantly (P <.01)
      in the 10-cm and 20-cm jejunal remnant groups compared with controls. Absorption
      of 3-0 methylglucose was significantly decreased (P <.01) in both resected
      groups. Serum GLP-2 levels were increased significantly (P <.05) when compared
      with controls in both resection groups. CONCLUSIONS: Increased serum GLP-2 levels
      were found in the ileocecal resection rat model, and these levels correlated with
      morphologic adaptation. However, this morphologic adaptation was not sufficient
      to restore nutrient absorption as shown by weight changes and 3-0 methylglucose
      absorption. Thus, the original hypothesis of this study is incorrect: systemic
      GLP-2 levels do not limit adaptation following distal ileocecal resection.

PMID- 11329582
TI  - Surgical resection and chemotherapy improve survival rate for patients with
      hepatoblastoma.
AB  - BACKGROUND: The authors reviewed retrospectively their experience in 30 children
      with hepatoblastoma (HB). Despite an increased trend in the incidence of HB
      during the last 2 decades, an encouraging cure rate has been achieved with
      complete resection of the tumor and chemotherapy before or after surgery with
      cisplatin plus doxorubicin (Adriamycin) or cisplatin plus vincristine plus 5
      Fluorouracil. RESULTS: There were 10 female and 20 male patients. For the period
      from 1963 to 1980 there were 8 patients, and for the period from 1981 to 1998
      there were 22 patients. Their mean age at surgery was 16 months (range, 3.5
      months to 5.5 years). Tumors were localized to the right lobe in 10 (42%), to the
      left lobe in 7 (29%), and in both lobes in 7 (29%) of the resected patients.
      Tumors were greater than 10 cm in size in 16 (67%) of these patients. Twenty-four
      patients (80%), underwent liver resection before or after chemotherapy. One
      patient (3%) with an unresectable tumor received chemotherapy and a liver
      transplant. In 5 patients (17%) the hepatic involvement was too extensive for
      resection. The types of resection performed were right lobectomy in 7, left
      lobectomy in 6, right trisegmentectomy in 8, left trisegmentectomy in 2, and
      middle hepatectomy in 1. The overall survival rate for 35 years of the study was
      60% (18 of 30). With the association of surgery and chemotherapy (1981 through
      1998) survival rate is 82% (14 of 17). Overall median follow-up in our study is 8
      years (range, 2.5 to 24 years). CONCLUSIONS: There has been a dramatic
      improvement in the results of treatment of hepatoblastoma. Formerly, only 25% to
      30% of patients were cured, whereas today, with combination of chemotherapy and
      surgery, 75% to 80% may be cured.

PMID- 11329583
TI  - Abdominal injuries associated with thoraco-lumbar fractures after motor vehicle
      collision.
AB  - PURPOSE: The goal of the current study was to evaluate the risk of intraabdominal
      injury in children who sustained spinal fractures in a motor vehicle collision
      (MVC). METHODS: Between 1980 and 1999, 48 patients, 24 girls and 24 boys, with a
      mean age of 12.8 years (range, 4 to 17) were reviewed. Twenty-nine were rear seat
      passengers, 12 front seat, and 7 unknown. Fifty-eight percent wore a seat belt.
      Thirty fractures involved the lumbar spine, 12 the thoracic, and 6 combined.
      Computed tomography (CT) scan, abdominal ultrasound, and peritoneal lavage were
      used to screen for abdominal injuries. RESULTS: Twenty-two of 48 patients had an
      intraabdominal injury. Eighteen (38%) required an early (<24 hours; n = 12) or
      delayed (n = 6) therapeutic laparotomy. Fourteen patients were rear seat
      passengers, 15 wore a seat belt, and 13 had an abdominal wall ecchymoses (AWE).
      They were 17 lumbar fractures (13 Chance) and one thoracic. The most common
      findings at laparotomy were hollow viscus injury (n = 12), mesenteric tear (n =
      9), and solid organ injury (n = 8). Seventy-two percent of patients presenting
      with a lumbar fracture and AWE needed a therapeutic laparotomy. The overall
      survival rate was 98% with only 1 death. The mean hospital stay was 22.4 days. In
      this study, 38% of patients presenting with a spinal fracture required
      laparotomy, 68% of whom had simultaneous lumbar fracture and AWE. CONCLUSION: In
      light of these results, the authors propose that laparoscopy or laparotomy should
      be strongly considered in patients sustaining lumbar fracture and AWE after MVC.
      J Pediatr Surg 36:760-762.

PMID- 11329584
TI  - Correlation between parental perception and actual childhood patterns of bicycle
      helmet use and riding practices: implications for designing injury prevention
      strategies.
AB  - BACKGROUND/PURPOSE: Bicycle injuries account for 10% of all pediatric traumatic
      deaths. Bicycle helmets have proven to decrease morbidity and mortality, yet
      trauma data show low helmet use among injured children. However, owning a bicycle
      helmet does not universally result in a child wearing a helmet. Furthermore, we
      hypothesize that parental perception of their children's use of the bicycle
      helmet may not reflect accurately true utilization by their child. To investigate
      this hypothesis the authors examined both parents' and their children's reports
      of bicycle ownership, supervision, riding patterns, and helmet use. METHODS: A
      random sample of grade 5 and 6 students (ages 8 to 12) and their parents were
      surveyed about bicycle ownership, riding patterns, supervision, and helmet use.
      The children and their guardians responded independently to the questionnaire.
      Statistical analysis was performed using the chi(2) test when indicated. RESULTS:
      Eighty-eight of 102 children (86%) responded. This represented 56% girls and 44%
      boys aged 8 to 12 years. Sixty-nine of 90 (77%) of the parents returned the
      survey. Ninety-six percent of the children owned a bicycle. A total of 87.5% of
      children owned a bicycle helmet. Eighty percent of the time children ride their
      bicycles on the road or sidewalk, with less then 20% on marked trails or parks.
      Parents reported that their children wear a helmet 90% of the time. In contrast,
      children report no helmet use in up to 61% of riding instances (P <.05). Parents
      themselves do not wear a helmet in greater then 60% when riding, which is
      correlated by their children. Seventy-one percent of the children report that
      they ride unsupervised the majority of the time. CONCLUSIONS: Bicycle and bicycle
      helmet ownership is high among this study group. There is a significant
      possibility that children will ride unsupervised, in at-risk situations, without
      wearing a helmet. Parental perceptions about bicycle helmet use by their children
      may not accurately reflect true utilization. In this study group parents appear
      as poor role models for their children. Injury prevention strategies need to
      focus on children and adults to improve effectiveness.

PMID- 11329585
TI  - Results and complications of laparoscopic surgery for pediatric varicocele.
AB  - BACKGROUND: The aim of this study was to evaluate the results and complications
      of laparoscopic varicocelectomy in children. METHODS: Over a 36-month period, 211
      children underwent laparoscopic treatment of varicocele. Their ages ranged
      between 6 and 17 years; the varicocele was located on the left side in 209 cases
      (99.1%) and was bilateral in 2 (0.9%). In 195 patients the laparoscopic
      transperitoneal approach was used and in 16 retroperitoneoscopy was used. Thirty
      children (14.2%) underwent ligation of the veins alone, and 181 (85.8%) underwent
      ligation of testicular veins and artery. In 15 (7.1%) cases an additional
      procedure was applied during the same operation. RESULTS: Average operating time
      was 30 minutes and hospitalization about 24 hours. At an average follow-up of 26
      months, there were 19 (9%) postoperative complications: 14 children had a left
      hydrocele, 3 children a scrotal emphysema, and 2 an umbilical granuloma. There
      were 5 recurrences of varicocele in our series: 2 (2 of 30, 6.6%) after the
      Ivanissevitch procedure, and 3 (3 of 181, 1.6%) after Palomo's. Testicular
      atrophy did not occur in any patient of this series. CONCLUSIONS: This
      preliminary experience shows that the results of the laparoscopic approach are
      comparable to those of the open approach. The ligation of testicular veins and
      artery is preferable to the ligation of the testicular veins alone. Hydrocele
      seems to be the most frequent postoperative complication and a potential problem,
      especially in children operated on with the Palomo procedure.

PMID- 11329586
TI  - Structural immaturity of the heart in congenital diaphragmatic hernia in rats.
AB  - PURPOSE: The form and function of the heart are the final result of an
      integration of cells, tissues, and extracellular material. The extracellular
      matrix (ECM) is a complex array of different molecular components, and it plays
      an important role for the transfer of mechanical force in both contraction and
      relaxation phases in the cardiac cycle. ECM plays also a significant role in the
      development of the heart. The aim of this study was to evaluate the expression of
      important ECM components in the heart of rats with induced CDH to test the
      hypothesis that an alteration of ECM may contribute to the cardiac
      maldevelopment, which recently has been identified as a contributive factor for
      the high mortality rate in babies with congenital diaphragmatic hernia (CDH).
      METHODS: CDH model was induced in pregnant rats after administration of 100 mg of
      nitrofen on day 9.5 of gestation (term, 22 days). In control animals the same
      dose of olive oil was given without nitrofen. Cesarean section was performed on
      day 21 of gestation. The fetuses were divided into 2 groups: normal control (n =
      10) and nitrofen-induced CDH (n = 10). Reverse transcription polymerase chain
      reaction (RT-PCR) was performed to evaluate the relative amount of tropoelastin
      and alpha1 (I) procollagen mRNA expression. Elastin protein content was measured
      using enzyme-linked immunosorbent assay (ELISA). RESULTS: There was a reduction
      in tropoelastin mRNA (P <.05) and procollagen mRNA (P <.05) in CDH compared with
      controls. The cardiac alpha-elastin content also was reduced in CDH (P <.01).
      CONCLUSIONS: The reduced cardiac tropoelastin and procollagen gene expression and
      the reduced alpha-elastin content indicate that the heart in CDH structurally is
      immature. The reduced production of cardiac ECM may contribute to a contractile
      dysfunction, which makes the heart unable to respond to the hemodynamic load
      accompanying persistent pulmonary hypertension (PPH).

PMID- 11329587
TI  - Jejunoileal atresia and associated malformations: correlation with the timing of
      in utero insult.
AB  - PURPOSE: Duodenal atresia is associated with a higher incidence of associated
      congenital malformations than jejunoileal atresia, supporting the hypothesis that
      the duodenal obstruction occurs early in fetal life. In this study, the authors
      analyzed the incidence of major associated malformations in jejunal atresia (JA)
      and ileal atresia (IA) to determine if there is a positive correlation between
      the proximity of the intestinal atresia and the association of other major
      anomalies. METHODS: Records of all patients with jejunoileal atresias treated at
      the authors' institution between 1980 and 1997 were examined. RESULTS: There were
      83 patients with jejunoileal atresias, 38 with JA, and 45 with IA. Sixteen (42%)
      of the JA patients had an associated major congenital malformation, whereas only
      1 (2%) of the IA patients had an associated malformation. A single atresia was
      found in 18 (47%) of JA patients and 41 (91%) of IA patients. Twenty (53%) of the
      JA patients had either multiple or apple-peel atresia. Thirteen patients (16%)
      died, 11 with JA, and 2 with IA. Of the 11 patients with JA who died, 6 had
      multiple atresias, 4 had cystic fibrosis, and 1 had small bowel volvulus.
      CONCLUSION: The higher incidence of associated major congenital extraintestinal
      malformations in JA compared with IA patients suggests that some cases of JA may
      arise from a malformative process.

PMID- 11329588
TI  - Intestinal neuronal dysplasia: results of treatment in 33 patients.
AB  - PURPOSE: Intestinal neuronal dysplasia (IND) is a disease of the enteric nervous
      system, which clinically resembles Hirschsprung's disease. The authors reviewed
      their experience of IND over an 8-year period. METHODS: Between 1992 and 1999,
      418 patients underwent rectal suction biopsy for persistent constipation. Thirty
      three (7.8%) patients had histologic evidence of IND. There were 26 boys and 7
      girls (age range, 1 week to 10 years). The diagnosis of IND was based on the
      presence of hyperganglionosis of the submucous plexus and giant ganglia and at
      least one of the following features in rectal biopsies: (1) ectopic ganglia, (2)
      increased acetylcholinesterase (AChE) activity in the lamina propria, and (3)
      increased AChE nerve fibers around the submucosal blood vessels. All patients
      were started on laxatives with or without enemas after the diagnosis was made.
      Patients have been followed up from 1 to 8 years (mean, 2.4 years). RESULTS:
      Twenty-one (64%) patients had a good response to conservative management and
      currently have normal bowel habits. Twelve patients (36%) underwent internal
      sphincter myectomy after failed conservative management. Seven of these patients
      now have normal bowel habits. Two patients are able to stay clean with regular
      enemas. Three patients who continued to have persistent constipation after
      myectomy and underwent resection of redundant and dilated sigmoid colon now have
      normal bowel habits. CONCLUSION: The majority of patients with IND can be treated
      successfully with conservative treatment.

PMID- 11329589
TI  - Clinical versus sonographic evaluation of acute appendicitis in children: a
      comparison of patient characteristics and outcomes.
AB  - PURPOSE: Abdominal sonography has gained popularity in establishing the diagnosis
      of appendicitis in children with equivocal clinical presentations. However, no
      clear outcome benefits have been demonstrated to date. The authors conducted a
      retrospective study to compare the characteristics and outcomes of patients
      undergoing appendectomy after clinical evaluation only with those undergoing the
      procedure after sonography. METHODS: The charts of 454 consecutive patients
      undergoing appendectomy for acute appendicitis between January 1, 1998 and
      December 4, 1999 were reviewed. Patients operated on after clinical evaluation
      only were compared with patients operated on after abdominal sonography. RESULTS:
      Forty-two percent of patients (n = 191) constituted the sonography group. When
      compared with the clinical group, these patients had higher prevalence of female
      gender (52% v 38%; P =.004), longer symptom duration (2.2 +/- 2.5 v 1.6 +/- 1.6
      days; P =.003), higher incidence of preoperative in-patient observation (19% v
      4%; P <.001), longer duration between evaluation and operation (8.0 +/- 3.9 v 4.9
      +/- 2.9 hours; P <.001), higher incidence of normal appendices on pathologic
      examination (13% v 6%; P =.006), and higher incidence of postoperative abscesses
      or phlegmons (4.4% v 1.2%; P =.04). The groups did not differ significantly in
      age, hospital stay, incidence of complicated appendicitis, or incidence of wound
      infection. CONCLUSIONS: Patients undergoing sonography before appendectomy have a
      longer delay before operation, a higher rate of misdiagnosis, and more
      postoperative complications. Limiting sonography to truly equivocal cases and
      using it early in the diagnostic workup may improve outcomes in this group of
      patients.

PMID- 11329590
TI  - The multiple facets of pulmonary sequestration.
AB  - PURPOSE: The goal of this study was to identify the proportion of sequestrations
      that were atypical or associated with other entities, such as congenital cystic
      adenomatoid malformations, communicating bronchopulmonary foregut malformations,
      bronchogenic cyst, and scimitar syndrome. METHODS: All charts of patients with
      pulmonary sequestration admitted at 2 children's hospitals from 1982 to July 1999
      were reviewed retrospectively. The authors included all anomalies with a systemic
      arterial supply or without bronchial connection. RESULTS: Only 22 of the 39
      patients (56%) had a classic isolated extralobar or intralobar sequestration,
      whereas the others presented with a spectrum of anomalies. Of the 13 cases
      diagnosed prenatally, 85% were asymptomatic at birth. In contrast, 26 cases
      diagnosed postnatally were all symptomatic, with those patients less than 2 weeks
      old presenting with various degrees of respiratory distress, and those older than
      2 weeks old presenting with respiratory infections. The correct diagnosis was
      made preoperatively in 59% of cases. Only 4 patients did not undergo resection of
      their lesion, of which, 1 underwent interventional radiology with embolization of
      the anomalous arterial supply. Follow-up issues of importance included pneumonia,
      asthma, gastroesophageal reflux, and pectus excavatum. CONCLUSIONS:
      Sequestrations represent a spectrum of anomalies that overlap with other lung
      lesions. To facilitate management, they should be described according to their
      (1) connection to the tracheobronchial tree, (2) visceral pleura, (3) arterial
      supply, (4) venous drainage, (5) foregut communication, (6) histology, (7)
      mixed/multiple lesions, and (8) whether there are associated anomalies. Surgeons
      should be aware that approximately 50% of sequestrations could be atypical or
      associated with other anomalies. This should be kept in mind when weighing the
      benefits of resection versus conservative management of pulmonary sequestrations.

PMID- 11329591
TI  - Additional medical information: prevalence, source, and benefit to parents.
AB  - PURPOSE: The aim of this study was to (1) characterize the source of additional
      medical information acquired by parents and (2) to verify how much information is
      correctly interpreted and remembered correctly. METHODS: A cross-sectional
      prospective study was made of parents of 108 children with surgical diseases
      consecutively admitted to a children's hospital in 1999. The median age of the
      children was 3 years (range, 0.01 to 16), and that of parents was 34 years
      (range, 18 to 54). Parental knowledge and understanding of their child's illness,
      operation, potential operative risk, and long-term outcome were scored on the
      basis of (1) parents' self appraisal (questionnaire) and (2) objective evaluation
      (interview) performed by one investigator not involved in the child's care.
      RESULTS: Parents' education included a university degree (15%), entry examination
      for university (13%), basic educational qualification (47%), and no educational
      qualification (15%). Additional medical information was obtained by 77% of the
      parents (63% from general practitioner, 46% from books, 31% from popular
      magazines, 24% from internet). Inadequate knowledge of illness and treatment was
      highlighted in 12% and 19% of the assessment made by interview, respectively,
      compared with 8% and 14% of the self appraisals. Inadequate knowledge of
      operative risk was higher in the assessment made by interview (42%) compared with
      self appraisal (9%; P <.0001). Similarly, inadequate knowledge of long-term
      outcome was higher in the interview (28%) compared with self appraisal (13%; P
      <.05). Acquisition of additional medical information irrespective of the source
      did not affect the accuracy of parental knowledge. Medical knowledge was more
      accurate in parents of children who required major operations and in those with
      higher educational qualifications (P <.05). CONCLUSIONS: Parents commonly obtain
      additional medical information. However, this information does not necessarily
      improve parents' understanding of the child's operative risk and long-term
      problems. Parents' perception of having adequate medical information often is
      incorrect.

PMID- 11329592
TI  - Colostomy for anorectal anomalies: high incidence of complications.
AB  - PURPOSE: The aim of this study was to characterize the type and incidence of
      complications related to colostomy formation in newborn infants with anorectal
      anomalies. METHODS: The authors reviewed a 5-year (1994 to 1999) experience of a
      single institution in the management of neonates with high and intermediate
      anorectal anomalies who required colostomy at birth. Patients with colostomy
      still in place have been excluded from the study to maximize the chances of
      detecting colostomy-related complications. RESULTS: There were 80 neonates with
      anorectal malformations, of whom, 49 (31 boys and 18 girls) were included in the
      study. The site of colostomy was sigmoid colon (n = 32), transverse colon (n =
      7), and descending colon (n = 10). Thirty-nine colostomies were loop, and the
      remaining 7 were divided. The median birth weight was 2.96 kg (range, 1.46 to
      3.88). The age at colostomy formation was 2 days (range, 1 to 210). Mechanical
      complications related to colostomy formation were observed in 16 infants (32%)
      with 3 infants having more than 1 mechanical complication. These included
      prolapse in 8 (50%), intestinal obstruction (adhesions, intussusception, and
      volvulus) in 7 (44%), and skin dehiscence in 3 (19%). One neonate had necrotizing
      enterocolitis (NEC) after colostomy formation. Urinary tract infection was
      observed after colostomy in 14 infants (29%). The incidence of urinary tract
      infection was not higher in infants who had loop colostomy (11 of 39, 28%)
      compared with infants who had divided colostomy (3 of 10, 30%). There were no
      differences in the incidence of colostomy-related complications and urinary tract
      infection between male and female infants. There were no deaths in this series.
      CONCLUSIONS: Formation of colostomy for anorectal anomalies should not be
      considered a minor procedure. In our experience the incidence of complications
      after colostomy formation is high. The incidence of urinary tract infections does
      not seem to be affected by the type of colostomy performed.

PMID- 11329593
TI  - The clinical significance of thrombocytopenia in neonates with necrotizing
      enterocolitis.
AB  - PURPOSE: The aim of this study was to evaluate the clinical significance of low
      platelet count in the surgical management of neonates with necrotizing
      enterocolitis (NEC). METHODS: The clinical course of 58 consecutive neonates with
      advanced NEC (Bell's stages II or III) treated in the authors' hospital between
      1995 and 1998 was reviewed. NEC in neonates who required operation was classified
      as isolated, multifocal, or pan-intestinal. Severe thrombocytopenia was defined
      as platelet count less than 100 x 10(9)/L. Rapid fall in platelet count was
      defined as fall greater than 150 x 10(9)/L within 24 hours to a level less than
      100 x 10(9)/L. RESULTS: Median birth weight was 1,564 g (range, 550 to 4,270) and
      gestational age was 31 weeks (range 23 to 41). Twenty-two neonates (38%) were
      below 1,000 g. Age at the onset of the disease was 13 days (range, 1 to 62). NEC
      was treated medically in 7 neonates (12%). Indications for operation included
      pneumoperitoneum in 23 neonates (45%), clinical deterioration in 19 (37%), and
      intestinal obstruction in 9 (18%). The nadir platelet count (lowest level during
      the course of disease) was lower in patients with stage III disease than in
      patients with stage II disease (P <.05). The greater the extent of the disease,
      the lower the platelet count (P =.012). The nadir platelet count was lower in
      infants who died than in survivors (P <.05). None of the patients with platelet
      count greater than 100 x 10(9)/L died. In predicting intestinal gangrene, severe
      thrombocytopenia has a sensitivity of 69%, specificity of 60%, and positive
      predictive value of 89%; rapid fall in platelet count has a sensitivity of 32%,
      specificity of 89%, and positive predictive value of 92%. CONCLUSIONS: (1) A
      platelet count less than 100 x 10(9)/L or a rapid fall in platelet count
      represent poor prognostic factors. (2) Monitoring the platelet count during the
      course of NEC is useful; however, it cannot be used in isolation to predict the
      extent of the disease or survival rate.

PMID- 11329594
TI  - Prenatal diagnosis of esophageal atresia using sonography and magnetic resonance
      imaging.
AB  - BACKGROUND: The diagnosis of esophageal atresia may be suspected on prenatal
      ultrasound scan in fetuses with a small or absent stomach or unexplained
      polyhydramnios. However, these findings are thought to have a low positive
      predictive value and clinical decisions affecting timing or site of delivery may
      be made erroneously. The authors evaluated the accuracy of fetal sonography
      followed by magnetic resonance imaging (MRI) for the diagnosis of this lesion.
      METHODS: Fetuses considered to be at risk for esophageal atresia based on
      detailed obstetric sonography underwent fetal MRI using a single-shot rapid
      acquisition technique, and the T(2)-weighted images were evaluated prospectively.
      Scans were considered to be positive if the proximal esophagus was dilated, and
      the distal esophagus was not seen and negative if the esophagus was visualized
      throughout its length. RESULTS: Ten fetuses underwent MRI scanning. All had a
      small or absent stomach bubble with unexplained polyhydramnios. Four scans were
      considered to be negative for esophageal atresia; all 4 were found to have a
      normal esophagus after delivery. Six scans were considered to be positive; 5 had
      esophageal atresia (2 with tracheoesophageal fistula and 3 without), and one had
      a neurologic syndrome with a normal esophagus. CONCLUSIONS: Magnetic resonance
      imaging appears to be accurate for establishing or ruling out a prenatal
      diagnosis of esophageal atresia, and should be considered in fetuses who are at
      high risk based on ultrasound findings.

PMID- 11329595
TI  - Evaluation of minimally invasive approaches to achalasia in children.
AB  - BACKGROUND: Achalasia is an uncommon disease in children, but when present can
      result in severe disabling symptoms often requiring surgical intervention. This
      report describes the authors' experience with thoracoscopic (TH) and later
      laparoscopic Heller (LH) myotomy for definitive treatment of this disease.
      METHODS: Nine patients with achalasia were referred for surgical therapy. Ages
      ranged from 5 to 17 years and weight from 23 to 78 kg. All had undergone at least
      one dilatation with recurrence of symptoms. The first 4 were treated by TH and
      the last five by LH. The 5 LH procedures also included a partial fundoplication.
      RESULTS: All procedures were completed successfully using minimally invasive
      techniques. Operating times averaged 95 minutes for TH and 62 minutes for LH. One
      patient undergoing TH had a small esophageal perforation repaired primarily. The
      other 3 TH patients were started on clear liquids within 1 day and discharged on
      day 2. One patient had recurrent symptoms at 6 months and underwent a LH for an
      incomplete TH. All 5 LH patients were discharged on postoperative day 1. One had
      an esophageal perforation 4 days after operation requiring laparoscopic repair.
      Seven of 9 patients are asymptomatic. Studies of pH levels in 2 asymptomatic TH
      patients show mild gastroesophageal reflux (GER). CONCLUSIONS: Minimally invasive
      Heller myotomy is a safe and effective procedure in children. TH results in a
      slightly longer operating time and hospital stay and, without a partial
      fundoplication, also may be associated with a higher incidence of silent GER.
      From these results, we prefer LH with a Dor fundoplication for treatment of
      achalasia in children.

PMID- 11329596
TI  - One-trocar surgery: a less invasive videosurgical approach in childhood.
AB  - BACKGROUND/PURPOSE: Laparoscopic techniques and instruments are evolving to
      lessen the invasiveness of this surgical approach. The authors present their
      experience with the videosurgical approach using only 1 trocar. METHODS: Between
      October 1997 and January 2000 the authors performed 59 videosurgical procedures
      using a 1-trocar approach (mean age, 11.5 years; range, 4 to 18 years). A 10-mm
      Hasson trocar was inserted in an "open" fashion either through the umbilicus
      (laparoscopy) or below the apex of the 12th rib (retroperitoneoscopy). An
      operative laparoscope was used in all cases. The operations were 18
      retroperitoneoscopic Palomo varicocelectomies, 1 retroperitoneoscopic renal
      biopsy, 38 appendectomies, and 2 ileal resections (Meckel's diverticulum,
      duplication cyst). For appendectomies and ileal resections, the corresponding
      intestinal loop was grasped and exteriorized through the umbilicus to perform
      conventional surgery. RESULTS: Mean operating time was 50.9 minutes (range, 30 to
      120) for laparoscopies and 44 minutes (range, 15 to 80) for retroperitoneoscopy.
      There were 11 conversions (8 appendectomies, 3 varicocelectomies) and no
      postoperative complications. CONCLUSIONS: "One-trocar surgery" is safe,
      effective, and fast with a low complication rate and excellent cosmetic results.
      The authors believe it is the least invasive as well as the most effective
      approach in the treatment of varicocele, appendicitis, and selected intestinal
      diseases.

PMID- 11329597
TI  - Significance of the clinical course and early upper gastrointestinal studies in
      predicting complications associated with repair of esophageal atresia.
AB  - BACKGROUND/PURPOSE: In many centers, use of upper gastrointestinal (UGI) contrast
      studies in the early postoperative period after esophageal atresia (EA) repair is
      considered routine. Indications for this are many, including searching for
      existing problems and predicting future complications. However, most major
      complications, both early and late, usually are identified clinically before any
      radiologic studies. The purpose of this study was to investigate factors that may
      anticipate the development of postoperative complications after EA repair,
      looking particularly at the predictive value of routine early postoperative UGI
      studies. METHODS: A total of 111 consecutive cases of EA were identified
      retrospectively over a 10-year period from 2 major Canadian pediatric health
      centers. One hundred one were associated with a distal tracheoesophageal fistula
      (TEF), of which, 90 had repairs. Ninety-seven percent of these had a UGI study at
      a median of 9.1 postoperative days (range, 2 to 23) before consideration of oral
      feeding. Charts were reviewed looking at patient variables, surgical factors,
      early UGI findings, and postoperative courses. Complications that required
      intervention were noted, including anastomotic leaks, gastroesophageal reflux
      (GER), strictures, and recurrent and missed fistulae. All initial UGI studies
      were reexamined by 1 of 2 pediatric radiologists. Logistic regression was used to
      examine relationships between these clinical and radiologic variables and
      outcomes. RESULTS: Of the variables analyzed, univariate analysis showed
      clinically significant leaks to be associated with intraoperative factors
      (subjective degree of anastomotic tension, and the use of myotomies) and early
      postoperative clinical evidence suggesting a leak. In a multivariate model, all
      remained independently significant except for the use of myotomies. Later
      development of clinically significant GER also was associated with the degree of
      tension. It had no relationship, however, with findings of dysmotility,
      esophageal shortening, or reflux at the initial UGI study. Development of a
      stricture requiring dilatations or resection was associated with a history of
      clinically evident GER only; no relationships were seen with a history of an
      anastomotic leak or any other clinical, operative, or radiographic variables.
      Missed or recurrent fistulae were all suspected clinically before radiologic
      confirmation. CONCLUSIONS: Early and late complications after repair of EA can be
      identified and potentially anticipated based on clinical findings at the time of
      repair and during the postoperative period. The use of early "routine" UGI
      studies, with no suspicion of a problem, has little value in terms of predicting
      complications or future clinical course.

PMID- 11329598
TI  - Long-term outcome after nonoperative management of complete traumatic pancreatic
      transection in children.
AB  - PURPOSE: The treatment of complete pancreatic transection (CPT) from blunt trauma
      remains controversial. To determine the natural history and long-term outcome of
      nonoperative management of CPT, we analyzed all such patients over the last 10
      years at a level I trauma center. METHODS: Retrospective analysis between 1990
      and 1999 was performed on 10 consecutive patients. Complete records were
      available for 9 patients. Data pertaining to their trauma admission, plus long
      term radiologic and clinical outcome were analyzed. RESULTS: There were 6 boys
      and 3 girls with a median age of 8 years (range, 4 to 16 years) and a median
      injury severity score (ISS) of 25. All patients displayed CPT on admission
      computed tomography (CT) scan. Four patients (44%) had associated intraabdominal
      injuries, but only 2 were significant. All patients were treated nonoperatively.
      Four patients (44%) had pseudocysts, and 3 required percutaneous drainage. Other
      complications included a single drainage of subphrenic collection, 1 inadvertent
      removal of drainage catheter, and 2 cases of line sepsis. The duration of
      percutaneous drainage was 14 to 60 days. The median length of hospitalization was
      24 days (range, 6 to 52 days). After median follow up of 47 months, no patients
      showed exocrine or endocrine insufficiency. One patient had abdominal pain not
      related to the pancreatic injury. Follow-up abdominal CT scans in 8 of 9 patients
      showed complete atrophy of the body and tail in 6 patients and 2 completely
      normal glands. CONCLUSIONS: Pancreatic transection is rare and commonly is found
      in isolation of other major abdominal injuries. No patients required surgery for
      their pancreatic transection. Pseudocysts can be managed effectively with
      percutaneous drainage. After a median follow-up of 47 months, no patients had
      endocrine or exocrine dysfunction. Anatomically, the distal body and tail usually
      atrophies; however, occasionally, the gland can heal and appear to recanalize. To
      the authors' knowledge, this is the first report to show the effectiveness of
      nonoperative management after complete pancreatic transection.

PMID- 11329599
TI  - Pediatric surgical images: MRCP evaluation of choledochal cysts.

PMID- 11329600
TI  - Laparoscopic repair of inguinal hernias in children.

PMID- 11329601
TI  - A method of derotation and duodeno-jejunostomy for high jejunal atresia.

PMID- 11329603
TI  - Developments in the treatment of choledochal cysts.

PMID- 11329605
TI  - Short bowel syndrome in infants and children: an overview.
AB  - Short bowel syndrome is a spectrum of malnutrition resulting from inadequate
      bowel length. In infant and pediatric patients, the most common causes are
      necrotizing enterocolitis, abdominal wall defects, jejunal ileal atresia, and mid
      gut volvulus. There appear to be regional variations in etiology. Since the
      publication of Wilmore's classic monograph in 1972, there have been significant
      improvements in monitoring and nutritional support. In the modern era, survival
      rate ranges from 80% to 94%, and the presence or absence the ileal cecal valve
      appears to not impact on mortality rate, but does significantly affect the length
      of time on total parenteral nutrition TPN. The most common morbidities remain
      sepsis, both central line related and bacterial overgrowth, and TPN cholestasis.
      Long-term recovery of these children often is remarkably normal, but there is a
      10% to 15% incidence of neurologic and developmental defects. The clinical and
      ethical considerations around the care of infants with 20 to 40 cm of residual
      bowel remains controversial, as does the place of intestinal transplantation,
      especially in patients developing gut failure in infancy. Perioperative surgical
      decision making plays a critical role in the long-term outcome of these patients.
      This chapter presents an overview of the current status of care and outcome in
      this difficult population; these topics are further expanded in subsequent
      chapters.

PMID- 11329606
TI  - Intestinal adaptation: structure, function, and regulation.
AB  - After massive small bowel resection (SBR), the remnant intestine undergoes an
      adaptive process characterized by increases in wet weight, protein and DNA
      content, villus height and crypt depth, and absorptive surface area. These
      changes are the result of a proliferative stimulus that increases crypt cell
      mitosis and augments cellular progression along the villus axis. Functionally,
      there is upregulation of the Na(+)/glucose cotransporter, Na(+)/H(+) exchanger,
      and other enzymes involved in intestinal digestion and absorption. These
      physiologic events are a compensatory response to the sudden loss of digestive
      and absorptive capacity by the remnant intestine. A major consequence of
      inadequate intestinal adaptation is lifelong dependence on parenteral nutrition,
      which results ultimately in cholestatic liver dysfunction. Furthermore,
      adaptation may be associated with changes in intestinal permeability and an
      increased risk of bacterial translocation and sepsis. Several mediators thought
      to be integral to the postresection adaptive response have been proposed,
      including luminal nutrients, gastrointestinal secretions, and humoral factors. A
      thorough understanding of intestinal adaptation will be essential in the rational
      development of new and innovative therapies that amplify this complex but
      important process.

PMID- 11329607
TI  - Enteral nutrition in short bowel syndrome.
AB  - Enteral nutrition in pediatric short bowel syndrome is a key component in
      facilitating a child's growth and development. In addition, aggressive use of
      enteral nutrition is not only one of the most important factors in promoting
      intestinal adaptation; it as well avoids the numerous complications associated
      with long-term parenteral nutrition. This manuscript will review the appropriate
      enteral nutrition for a child with short bowel syndrome. Issues to be addressed
      include appropriate enteral formula selection, solid food intake, enteral
      administration routes, and devices. Information presented is based on current
      research as well as experience with a large population of pediatric short bowel
      syndrome patients.

PMID- 11329608
TI  - Parenteral nutrition-associated cholestasis.
AB  - Cholestasis is a major complication that occurs frequently in patients with the
      short bowel syndrome and accounts for the majority of morbidity and mortality in
      this group of patients. The exact cause of this condition is not known and the
      etiology is likely multifactorial. Many new mechanistic insights into this
      disease are discussed and have paved the way for future investigation. For now,
      prompt recognition, early initiation of enteral feeding, prevention of
      overfeeding with parenteral nutrition, and agents that induce bile flow may be
      useful to prevent this catastrophic morbidity.

PMID- 11329609
TI  - Pharmacotherapy and growth factors in the treatment of short bowel syndrome.
AB  - A review of the pharmacologic substances and growth factors that have been
      studied experimentally and administered clinically for the management of short
      bowel syndrome is presented. The medical management of short bowel syndrome is
      multifaceted. In the acute phase, efforts focus on fluid and electrolyte
      management and the reduction of gastric acid output. As enteral feeding is
      initiated, antimotility and antisecretory agents may be effective in reducing
      gastrointestinal losses. Additional modalities of management, including nutrients
      and growth factors, may be directed at maximizing absorptive function beyond that
      which occurs with intestinal adaptation. Continued research aimed at further
      elucidating the process of intestinal adaptation may allow us to use the various
      peptides and hormones that act as growth factors for the bowel mucosa. Knowledge
      gained from these studies combined with gene therapy techniques will result in
      the permanent enhancement of intestinal function beyond the normal adaptation
      process, eliminate the dependence on total parenteral nutrition, and avoid the
      need for intestine transplantation.

PMID- 11329610
TI  - Surgical options for short bowel syndrome.
AB  - Most children with short bowel syndrome experience spontaneous small bowel
      adaptation over time. This allows the majority to be weaned from parenteral
      nutrition. There are, however, some children who cannot be weaned and are
      potential candidates for techniques to promote intestinal adaptation and
      intestinal lengthening. Here, surgical therapeutic options are described,
      literature reviewed, and reported results evaluated. Surgical procedures for
      children with short bowel syndrome have high complication and failure rates, but
      in most cases are a less invasive option than intestinal transplantation.

PMID- 11329611
TI  - Intestinal transplantation for children with short bowel syndrome.
AB  - Intestinal transplantation has emerged as a feasible alternative in the treatment
      of children with short gut syndrome. The challenges in the management of these
      patients include maintaining a tight balance between the degree of
      immunosuppression necessary to prevent graft-versus-host disease and rejection.
      At the same time, this amount of immunosuppression is associated with a high risk
      for lymphoproliferative disorders and intestinal-derived sepsis. Current 3-year
      patient and graft survival rates are 55% and 50%, respectively. The indications,
      morbidity, and timing for referral are discussed.

PMID- 11329612
TI  - Establishment and characterization of chondrocyte cell lines from the costal
      cartilage of SV40 large T antigen transgenic mice.
AB  - Complete understanding of the physiology and pathology of the cartilage is
      essential to establish treatments for a variety of cartilage disorders and
      defects such as rheumatoid arthritis, congenital malformations, and tumors of
      cartilage. Although synthetic materials have been used in many cases, they
      possess inherent problems including wear of the materials and low mechanical
      strength. Autograft has been considered very effective to overcome these
      problems. However, the limitation of the transplant volume is a major problem in
      autograft to be overcome. The costal cartilage is the most serious candidate for
      donor site transplantation, since it is the largest permanent hyaline cartilage
      in the body. To investigate the possibility using the costal cartilage as a
      transplant source, we have established and characterized three mouse chondrocyte
      cell lines (MCC-2, MCC-5, and MCC-35) derived from the costal cartilage of 8-week
      old male SV40 large T-antigen transgenic mice. At confluence, all the cell lines
      formed nodules that could be positively stained with alcian blue (pH 2.5). The
      size of nodules gradually increased during culturing time. After 2 and 6 weeks of
      culture, RT-PCR analysis demonstrated that all three cell lines expressed mRNA
      from the cartilage-specific genes for type II collagen, type XI collagen,
      aggrecan, and link protein. Furthermore, type X collagen expression was detected
      in MCC-5 and MCC-35 but not in MCC-2. Any phenotypic changes were not observed
      over 31 cell divisions. Immunocytochemistry showed further that MCC-2, MCC-5, and
      MCC-35 produced cartilage-specific proteins type II collagen and type XI
      collagen, while in addition MCC-5 and MCC-35 produced type X collagen. Treatment
      with 1alpha, 25-dihydroxyvitamin D(3) inhibited cell proliferation and
      differentiation of the three cell lines in a dose-dependent manner. These
      phenotypic characteristics have been found consistent with chondrocyte cell lines
      established from cartilage tissues other than costal cartilage. In conclusion,
      costal cartilage shows phenotypic similarities to other cartilages, i.e.,
      articular cartilage and embryonic limbs, suggesting that costal cartilage may be
      very useful as the donor transplantation site for the treatment of cartilage
      disorders. Furthermore, the cell lines established in this study are also
      beneficial in basic research of cartilage physiology and pathology.

PMID- 11329613
TI  - An insight into the mechanism of cytotoxicity of ricin to hepatoma cell: roles of
      Bcl-2 family proteins, caspases, Ca(2+)-dependent proteases and protein kinase C.
AB  - The ability of ricin, a type II ribosome-inactivating protein, to induce hepatoma
      cell (BEL7404) to apoptosis in vitro was examined by fluorescence microscopy,
      flow cytometry, and DNA fragmentation assay. As a Bcl-2 lacking model, BEL7404
      bore unique advantage to study the effect of over-expressing Bcl-2 on the
      apoptosis induced by the inhibitor of protein synthesis. By establishing a Bcl-2
      over-expressing cell line (BEL7404/ Bcl-2), we found that Bcl-2 could promote the
      survival of the hepatoma cell against ricin insult. The ricin-induced apoptosis
      of BEL7404 was accompanied by increased expression of Bak and decreased levels of
      Bcl-xl and Bax. Caspases and PARP cleavage activity were found to be implicated
      in the death process. Through the inhibitor tests, our results excluded the
      participation of calcium-dependent proteases or protein kinase C in the apoptotic
      process induced by ricin, though an elevation of intracellular calcium did occur
      as an immediate response to ricin treatment. Cycloheximide, another protein
      synthesis inhibitor, did synergistically enhance rather than inhibit the
      cytotoxicity of ricin to hepatoma cell BEL7404. Actually, cycloheximide alone was
      able to induce hepatoma cell BEL7404 to death that could also be inhibited by
      over-expressing Bcl-2. The elevation of apoptotic protein Bak was discussed to
      challenge the notion that ricin exerted its cytotoxicity through nonspecific
      inhibition of all the de novo protein synthesis.

PMID- 11329614
TI  - Mitogenic G(i) protein-MAP kinase signaling cascade in MC3T3-E1 osteogenic cells:
      activation by C-terminal pentapeptide of osteogenic growth peptide [OGP(10-14)]
      and attenuation of activation by cAMP.
AB  - In osteogenic and other cells the mitogen-activated protein (MAP) kinases have a
      key role in regulating proliferation and differentiated functions. The osteogenic
      growth peptide (OGP) is a 14 mer mitogen of osteogenic and fibroblastic cells
      that regulates bone turnover, fracture healing, and hematopoiesis, including the
      engraftment of bone marrow transplants. It is present in the serum and
      extracellular fluid either free or complexed to OGP-binding proteins (OGPBPs).
      The free immunoreactive OGP consists of the full length peptide and its C
      terminal pentapeptide OGP(10-14). In the present study, designed to probe the
      signaling pathways triggered by OGP, we demonstrate in osteogenic MC3T3 E1 cells
      that mitogenic doses of OGP(10-14), but not OGP, enhance MAP kinase activity in a
      time-dependent manner. The OGP(10-14)-induced stimulation of both MAP kinase
      activity and DNA synthesis were abrogated by pertusis toxin, a G(i) protein
      inhibitor. These data offer direct evidence for the occurrence in osteogenic
      cells of a peptide-activated, mitogenic Gi protein-MAP kinase-signaling cascade.
      Forskolin and dBu(2)-cAMP abrogated the OGP(10-14)-stimulated proliferation, but
      induced only 50% inhibition of the OGP(10-14)-mediated MAP kinase activation,
      suggesting additional MAP kinase-dependent, OGP(10-14)-regulated, cellular
      functions. Finally, it is demonstrated that OGP(10-14) is the active form of OGP,
      apparently generated proteolytically in the extracellular milieu upon
      dissociation of OGP-OGPBP complexes.

PMID- 11329615
TI  - Response of alkalinization or acidification by phytohemagglutinin is dependent on
      the activity of protein kinase C in human peripheral T Cells.
AB  - The increase of intracellular free calcium concentration ([Ca(2+)](i)) and
      protein kinase C (PKC) activity are two major early mitogenic signals to initiate
      proliferation of human T cells. However, a rapid change in intracellular pH
      (pH(i)), acidification or alkalinization during the activation, is also
      associated after these two signals. The aim of this study was to define whether
      the change in pH(i) is affected by calcium and protein kinase C (PKC), in
      phytohemagglutinin (PHA)-stimulated T cells. T cells were isolated from human
      peripheral blood. The [Ca(2+)](i) and the pH(i) were measured using,
      respectively, the fluorescent dyes, Fura-2, and BCECF. In addition, down
      regulation of PKC activity by PMA (1 microM, 18 h) was confirmed in these cells
      using a protein kinase assay. The results indicated that, (1) alkalinization was
      induced by PHA or PMA in T cells; the results of alkalinization was PKC-dependent
      and Ca(2+)-independent, (2) in PKC down-regulated T cells, PHA induced
      acidification; this effect was enhanced by pre-treating the cells with the
      Na(+)/H(+) exchange inhibitor, 5-(N,N-dimethyl)-amiloride, (DMA, 10 microM, 20
      min), (3) the acidification was dependent on the Ca(2+) influx and blocked by
      removal of extracellular calcium or the addition of the inorganic channel
      blocker, Ni(2+), and (4) Thapsigargin (TG), a Ca(2+)-ATPase inhibitor, confirmed
      that acidification by the Ca(2+) influx occurred in T cells in which PKC was not
      down-regulated. These findings indicate two mechanisms, alkalinization by PKC and
      acidification by Ca(2+) influx, exist in regulating pH(i) in T cells. This is the
      first report that PHA stimulates the acidification by Ca(2+) influx but not
      alkalinization in T cells after down-regulation of PKC. In conclusion, the
      activity of PKC in T cells determines the response in alkalinization or
      acidification by PHA.

PMID- 11329616
TI  - Modulation of intestinal and liver fatty acid-binding proteins in Caco-2 cells by
      lipids, hormones and cytokines.
AB  - Intestinal and liver fatty acid binding proteins (I- and L-FABP) are thought to
      play a role in enterocyte fatty acid (FA) trafficking. Their modulation by cell
      differentiation and various potential effectors was investigated in the human
      Caco-2 cell line. With the acquisition of enterocytic features, Caco-2 cells
      seeded on plastic progressively increased L-FABP quantities, whereas I-FABP was
      not detectable even very late in the maturation process. On permeable filters
      that improved differentiation markers (sucrase, alkaline phosphatase,
      transepithelial resistance), Caco-2 cells furthered their L-FABP content and
      expressed I-FABP. Western blot analysis showed a significant increase in I- and L
      FABP expression following an 8-hour incubation period with butyric acid, oleic
      acid, and phosphatidylcholine. However, in all cases, I-FABP levels were higher
      than L-FABP concentrations regardless of the lipid substrates added. Similarly,
      hydrocortisone and insulin enhanced the cellular content of I- and L-FABP whereas
      leptin triggered I-FABP expression only after an 8-hour incubation. Finally,
      tumor necrosis factor-alpha was more effective in increasing the cytosolic amount
      of I-FABP levels. In conclusion, our data demonstrate that I-FABP expression is
      limited to fully differentiated Caco-2 cells and can be more easily regulated
      than L-FABP by lipids, hormones, and cytokines.

PMID- 11329618
TI  - Suppressive role of endogenous regucalcin in the regulation of protein
      phosphatase activity in rat renal cortex cytosol.
AB  - The role of endogenous regucalcin, which is a regulatory protein of calcium
      signaling, in the regulation of protein phosphatase activity in the cytosol of
      rat renal cortex was investigated. Protein phosphatase activity toward
      phosphotyrosine, phosphoserine, and phosphothreonine was found in the cytosol of
      kidney cortex. The addition of regucalcin (50-250 nM) in the enzyme reaction
      mixture caused a significant decrease in protein phosphatase activity toward
      three phosphoamino acids. The effect of calcium (25 microM) and calmodulin (2.5
      microg/ml) in increasing protein phosphatase activity toward three phosphoamino
      acids was significantly decreased by the addition of regucalcin (100 nM). Protein
      phosphatase activity toward three phosphoamino acids was significantly increased
      in the presence of anti-regucalcin monoclonal antibody (10-50 ng/ml) in the
      enzyme reaction mixture. The effect of antibody (25 ng/ml) in increasing the
      enzyme activity was significantly inhibited by cyclosporin A (10(-5) M) or
      vanadate (10(-5) M). Regucalcin in the kidney cortex cytosol was clearly
      decreased by the administration of saline (0.9% NaCl) for seven days in rats.
      Protein phosphatase activity toward three phosphoamino acids was significantly
      decreased by saline administration. The effect of anti-regucalcin antibody (25
      ng/ml) in increasing protein phosphatase activity toward three phosphoamino acids
      was not seen in the renal cortex cytocol of saline-administered rats. The present
      study demonstrates that endogenous regucalcin plays a suppressive role in the
      regulation of protein phosphatase activity in the cytoplasm of rat kidney cortex.

PMID- 11329617
TI  - Ras-induced colony formation and anchorage-independent growth inhibited by
      elevated expression of Puralpha in NIH3T3 cells.
AB  - Levels of Puralpha, a conserved, sequence-specific single-stranded DNA and RNA
      binding protein, fluctuate during the cell cycle, declining at the onset of S
      phase and peaking at mitosis. In early G1 Puralpha is associated with the
      hypophosphorylated form of the retinoblastoma protein, Rb. Microinjection of
      purified Puralpha into NIH3T3 cells arrests the cell cycle at either G1/S or G2/M
      checkpoints with distinct morphological consequences. Here we ask whether
      expression of Puralpha can affect colony formation and anchorage-independent
      growth in ras-transformed NIH3T3 cells. Two to five-fold elevated levels of
      Puralpha in stably-transfected cell lines retard entry into and progression
      through S phase in both ras-transformed and non-transformed cells. Puralpha
      significantly inhibits colony formation by ras-transformed cells but not by non
      transformed cells. In addition, cells transfected to express Puralpha formed only
      about 1/5 the number of large colonies in soft agar as control-transfected cells,
      demonstrating a marked inhibition of anchorage-independent growth by Puralpha.
      Biochemical analysis of nuclear and cytoplasmic Puralpha proteins and confocal
      microscopic analysis of Puralpha location indicate that access of Puralpha to the
      nucleus is controlled by both protein modification and sequence domains within
      the protein. Analyses of deletion mutants identify Puralpha domains mediating
      nuclear exclusion, including several potential destruction motifs and a PEST
      sequence at aa's 215-231. In the nucleus Puralpha colocalizes with CDK2 and
      cyclin A. Puralpha and cyclin D1, however, do not colocalize in the nucleus. At
      mitosis Puralpha is visualized about the condensed chromosomes and in the
      cytoplasm, where it colocalizes with cyclin B1. The data indicate that the
      ability of Puralpha to interact with proteins regulating cell proliferation and
      transformation is controlled by signals that govern its intracellular
      localization.

PMID- 11329619
TI  - Epigallocatechin gallate protects U937 cells against nitric oxide-induced cell
      cycle arrest and apoptosis.
AB  - Ingesting phenolic phytochemicals in many plant products may promote health, but
      the effects of phenolic phytochemicals at the cellular level have not been fully
      examined. Thus, it was determined if the tea phenolic phytochemical,
      epigallocatechin gallate (EGCG), protects U937 human pro-monocytic cells against
      the nitrogen free radical, nitric oxide (*NO). Cells were incubated for 4-6 h
      with 500 microM S-nitrosoglutathione (GSNO), which generates *NO, but this did
      not induce single-strand breaks in DNA. Nevertheless, 82 +/- 4% of GSNO-treated
      cells, compared to only 39 +/- 1% of untreated cells, were arrested in the G(1)
      phase of the cell cycle. However, dosing the GSNO-treated cells with 9, 14, or 18
      microg/ml of EGCG resulted in only 74 +/- 8%, 66 +/- 1%, and 43 +/- 3% of the
      cells, respectively, in the G(1)-phase. Exposing cells to GSNO also resulted in
      the emergence of a sub-G(1) apoptotic cell population numbering 14 +/- 3%, but
      only 5 +/- 2%, 5 +/- 1%, and 2 +/- 0% upon dosing of the GSNO-treated cells with
      9, 14, and 18 microg/ml of EGCG, respectively. Furthermore, exposing cells to
      GSNO resulted in greater cell surface binding of annexin V-FITC, but binding was
      41-89% lower in GSNO-treated cells dosed with EGCG. Collectively, these data
      suggest that *NO or downstream products induced cell cycle arrest and apoptosis
      that was not due to single-strand breaks in DNA, and that EGCG scavenged
      cytotoxic *NO or downstream products, thus reducing the number of cells in a
      state of cell cycle arrest or apoptosis.

PMID- 11329620
TI  - Bruton's tyrosine kinase associates with the actin-based cytoskeleton in
      activated platelets.
AB  - Bruton's tyrosine kinase (Btk) plays a crucial role in the maturation and
      differentiation of B-lymphocytes and immunoglobulin synthesis. Recently Btk has
      been described to be present in significant amount in human platelets. To
      investigate the regulation of this kinase in the platelets we studied its
      subcellular redistribution in the resting and activated cells. In the resting
      platelets Btk was almost absent from the actin-based cytoskeleton. Upon challenge
      of the platelet thrombin receptor upto 30% of total Btk appeared in the
      cytoskeleton and the protein underwent phosphorylation on tyrosine. Translocation
      of Btk to the cytoskeleton but not aggregation was prevented by cytochalasin B,
      which inhibits actin polymerization. Wortmannin and genistein (inhibitors of
      phosphoinositide 3-kinase and protein tyrosine kinase, respectively) decreased
      while phenylarsine oxide (a tyrosine phosphatase inhibitor) increased the
      cytoskeletal content of Btk. The association of Btk with the cytoskeleton was
      regulated by integrin alpha(IIb)beta(3) and partly reversible. Taken together,
      these data suggest that Btk might be a component of a signaling complex
      containing specific cytoskeletal proteins in the activated platelets.

PMID- 11329621
TI  - Increased mRNA expression and protein secretion of interleukin-6 in primary human
      osteoblasts differentiated in vitro from rheumatoid and osteoarthritic bone.
AB  - We have investigated the expression and synthesis of potential bone-resorbing
      cytokines, interleukin-6 (IL-6), interleukin-1 (IL-1), and tumor necrosis factor
      (TNF) in rheumatoid arthritic (RA) and osteoarthritic (OA) bone, two common
      diseases which are associated with bone loss. Primary human osteoblast (hOB)
      cultures were established to determine the temporal mRNA expression of IL-6, IL-1
      (alpha and beta), and TNF (alpha and beta) in relation to osteoblast growth and
      phenotypic genes. IL-6 mRNA levels were found to be significantly higher (P <
      0.04) in both OA hOB (17 patients) and RA hOB (10 patients) compared to normal
      (NO) hOB (9 patients) and reached five-fold increases in OA hOB and 13-fold
      increases in RA hOB. Maximal levels of IL-6 are expressed at Day 21 which
      corresponds to the mineralization stage reflected by decreasing collagen I
      (alpha(1)), osteopontin, bone sialoprotein, alkaline phosphatase mRNA levels,
      while osteocalcin (OC) mRNA levels increased. IL-6 protein levels also were
      significantly higher (P < 0.05) in OA hOB and RA hOB compared to NO hOB. These
      increases were not attributable to sex or age of the donor bone. Neither the mRNA
      encoding IL-1(alpha and beta) and TNF(alpha and beta) nor the related proteins
      were detectable. These results indicate that differentiated OA hOB and RA hOB
      within a bone tissue-like matrix constitutively express and secrete high levels
      of IL-6. This inherent property suggests that these osteoblasts, independent of
      local inflammatory parameters, can contribute to enhanced recruitment of
      osteoclast progenitors and thereby bone resorption.

PMID- 11329622
TI  - Acrolein induces activation of the epidermal growth factor receptor of human
      keratinocytes for cell death.
AB  - Acrolein, which is a highly reactive formaldehyde generated by lipid
      peroxidation, can affect skin and cause various disorders. The effect of exposure
      of human keratinocytes to acrolein on cell surface-oriented signal transduction
      into cells was examined. Incubation of human keratinocytes with a relatively low
      concentration (50 microM) of acrolein caused a prompt and selective induction of
      tyrosine phosphorylation of the epidermal growth factor receptor (EGFR) as a 180
      kDa molecule during the period from 5-30 min after the start of incubation. This
      early event was followed by an increase in the density and number of
      phosphotyrosine-containing proteins during the period from 60-120 min after the
      start of incubation. The catalytic activity of EGFR as measured by the levels of
      autophorphorylation and phosphorylation of an exogenously added substrate,
      casein, in in vitro kinase assay, greatly increased as early as 1 min after the
      start of incubation and then decreased gradually 30 min later. MAP family
      kinases, including ERK, JNK, and p38 kinase, and the potentially downstream
      transcription factor c-Jun were all promoted for phosphorylation/activation
      during a period of 5-30 min. Selective prompt phosphorylation/activation of EGFR
      followed by phosphorylation of MAP family kinases and c-Jun and their blockade by
      a specific EGFR inhibitor, AG1478, suggested that activation of EGFR is the
      major, and possibly single, cell surface element for intracellular signal
      transduction in acrolein-treated cells. Incubation of human keratinocytes with 50
      microM of acrolein induced atypical apoptosis with morphologic apoptotic features
      with low-grade oligonucleoside-sized DNA fragmentation. Partial inhibition of
      such a cytopathic effect of acrolein on human keratinocytes by preincubation with
      AG1478 suggests the involvement of an EGFR-mediated signal pathway for atypical
      apoptosis. These results provide new information on acrolein-induced cell surface
      oriented signal transduction to human keratinocytes, and this information may be
      useful for understanding the pathogenesis of a number of skin diseases in
      response to environmental acrolein and acrolein-generating ultraviolet
      irradiation.

PMID- 11329623
TI  - Electromagnetic initiation of transcription at specific DNA sites.
AB  - Initiation of transcription by electromagnetic (EM) fields offers an insight into
      mechanism. EM field stimulated transcription appears to require specific DNA
      sequences, and these bases may be sites where EM fields generate large repulsive
      forces between chains by accelerating electrons that move within DNA. We can
      estimate the repulsion between chains by assuming that electron affinity is a
      measure of electron density at each base, and inversely related to the velocity
      of electrons (and the force). The repulsive force can be compared to the
      attraction between chains due to H-bonds. From the difference between repulsion
      and attraction, we show that sites rich in C and T, as in the specific sequences,
      would be more likely to come apart in EM fields. These calculations suggest a
      plausible mechanism for initiation of transcription by EM fields, and provide a
      rationale for specific sequences to function as EM field response elements.
      Electron flow could also be a factor in DNA chain melting due to Joule heating.

PMID- 11329624
TI  - Relative efficacies of indole antioxidants in reducing autoxidation and iron
      induced lipid peroxidation in hamster testes.
AB  - Increased iron stores are associated with free radical generation and
      carcinogenesis. Lipid peroxidation is involved in DNA damage, thus indirectly
      participating in the early steps of tumor initiation. Melatonin and structurally
      related indoles are effective in protecting against oxidative stress. The aim of
      the study was to compare the relative efficacies of melatonin, N-acetylserotonin
      (NAS), indole-3-propionic acid (IPA), and 5-hydroxy-indole-3-acetic acid (5HIAA)
      in altering basal and iron-induced lipid peroxidation in homogenates of hamster
      testes. To determine the effect of the indoles on the autoxidation of lipids,
      homogenates were incubated in the presence of each agent in concentrations of
      0.0, 0.01, 0.05, 0.1, 0.25, 0.5, 0.75, 1.0, 2.0, 2.5, or 5.0 mM. To study their
      effects on induced lipid peroxidation, homogenates were incubated with FeSO(4)
      (30 microM + H(2)O(2) (0.1 mM) + each of the indoles in the same concentrations
      as above. The degree of lipid peroxidation was expressed as concentrations of
      malondialdehyde + 4-hydroxyalkenals (MDA + 4-HDA) per mg protein. The indoles
      decreased both basal and iron-related lipid peroxidation in a concentration
      dependent manner. Melatonin reduced basal MDA + 4-HDA levels when used at the
      concentrations of 0.25 mM or higher, and prevented iron-induced lipid
      peroxidation at concentrations of 1.0, 2.0, 2.5, or 5.0 mM. The lowest effective
      concentrations of NAS required to lower basal and iron-related lipid peroxidation
      were 0.05 mM and 0.25 mM, respectively. IPA, only when used in the highest
      concentrations of 2.5 mM or 5 mM inhibited basal lipid peroxidation levels and it
      was ineffective on the levels of MDA + 4-HDA due to iron damage. 5HIAA reduced
      basal lipid peroxidation when used at concentrations of 0.25 mM or higher, and it
      prevented iron-induced lipid peroxidation only at the highest applied
      concentration (5 mM). In conclusion, melatonin and related indoles at
      pharmacological concentrations protect against both the autoxidation of lipids as
      well as induced peroxidation of lipids in testes. In doing so, these agents would
      be expected to reduce testicular cancer that is initiated by products of lipid
      peroxidation.

PMID- 11329625
TI  - Expression of translation initiation factor IF2 is regulated during osteoblast
      differentiation.
AB  - We isolated and characterized a cDNA for the N-terminal half of the eukaryotic
      initiation of translation factor 2 (cIF2) during a screen of chicken osteoblast
      cDNAs. The apparent size of the message for this protein, approximately 5.6 kb,
      is slightly larger in size than that for human IF2 (hIF2). There is a high degree
      of sequence similarity between the human and chicken N-terminal portions of the
      protein that extends to the encoding nucleotide sequence. The tissue specific
      expression pattern for cIF2 and hIF2 are similar, being moderately abundant in
      brain, liver, and skeletal muscle, and detectable in kidney, chondrocytes, and
      freshly isolated osteoblasts. The ratio of message for cIF2 to that of beta-actin
      was 0.10 and 0.18 for liver and brain. Message levels peak in osteoblasts between
      8 and 12 days of culture, coinciding with high levels of matrix protein
      synthesis. At peak expression, the ratio of cIF2:beta-actin for 8 day osteoblasts
      was 0.76. Treatment of osteoblast cultures with cycloheximide markedly reduces
      the level of cIF2 message indicating that novel protein synthesis is required for
      its expression. Hybridization of RNA samples from either chicken osteoblasts or a
      human osteoblast cell line with a probe for a subunit of human eukaryotic
      initiation of translation factor 2 (eIF2alpha), the housekeeping initiation
      factor, indicates that levels of eIF2 remain low. With hIF2, cIF2 represents the
      only other vertebrate homolog of IF2 for which a major portion of the coding
      sequence has been identified. This is the first report of regulated expression
      for a eukaryotic IF2 and is the first demonstration of its abundance in
      osteoblasts.

PMID- 11329626
TI  - Effects of cannabinoids on LPS-stimulated inflammatory mediator release from
      macrophages: involvement of eicosanoids.
AB  - Delta(9)-Tetrahydrocannabinol (Delta(9)-THC) is the major psychoactive component
      of marijuana and elicits pharmacological actions via cannabinoid receptors.
      Anandamide (AEA) and 2-arachidonoyl-glycerol (2-AG) are endogenous ligands for
      cannabinoid receptors, which because of their structural similarities to
      arachidonic acid (AA), AEA, and 2-AG could serve as substrates for lipoxygenases
      and cyclooxygenases (COXs) that metabolize polyunsaturated fatty acids to potent
      bioactive molecules. In this study, we have compared the effects of Delta(9)-THC,
      AEA, 2-AG, and another cannabinoid agonist, indomethacin morpholinylamide (IMMA),
      on lipopolysaccharide (LPS)-induced NO, IL-6, and PGE(2) release from J774
      macrophages. Delta(9)-THC, IMMA, and AEA diminish LPS-induced NO and IL-6
      production in a concentration-dependent manner. 2-AG inhibits the production of
      IL-6 but slightly increases iNOS-dependent NO production. Delta(9)-THC and IMMA
      also inhibit LPS-induced PGE(2) production and COX-2 induction, while AEA and 2
      AG have no effects. These discrepant results of 2-AG on iNOS and COX-2 induction
      might be due to its bioactive metabolites, AA and PGE(2), whose incubation cause
      the potentiation of both iNOS and COX-2 induction. On the contrary, the AEA
      metabolite, PGE(2)-ethanolamide, influences neither the LPS-induced NO nor IL-6
      production. Taken together, direct cannabinoid receptor activation leads to anti
      inflammatory action via inhibition of macrophage function. The endogenous
      cannabinoid, 2-AG, also serves as a substrate for COX-catalyzing PGE(2)
      production, which in turn modulates the action of CB2.

PMID- 11329628
TI  - Mike Rossi cut costs and his own job.

PMID- 11329629
TI  - In the market for an e-commerce future. Marketplace comparison: health care
      versus business.

PMID- 11329630
TI  - A for angst, P for panic C for calamity.

PMID- 11329631
TI  - Pressure cooker of an issue: control of food service.

PMID- 11329632
TI  - Blowing the whistle on reuse enforcement.

PMID- 11329633
TI  - Materials to services, management pays off.

PMID- 11329634
TI  - The leech therapy wave. They've proven their worth, but stocking them isn't easy.

PMID- 11329635
TI  - What makes a winner? Key characteristics of peak performing hospitals.
AB  - Peak-performing hospitals and systems not only provide high-quality care, they
      were actually able to report rising profit margins over the last year. Learn in
      detail about the eight characteristics that these peak performers share.

PMID- 11329636
TI  - Mission possible: community health.
AB  - VHA Health Foundation and the AHA's Health Research and Educational Trust
      surveyed 15 national community health award winners to learn how they have
      sustained their community health programs in a challenging economic environment.

PMID- 11329637
TI  - When does the board need its own legal counsel?

PMID- 11329638
TI  - Natural selection.
AB  - Complementary and alternative medicine (CAM) is a consumer-driven mode of care
      whose time has come. As one expert puts it: "Your biggest risk is not getting
      involved, not finding out what patients are doing." Learn how to integrate CAM
      into your other services and how to get your physicians' support.

PMID- 11329639
TI  - How to run effective board meetings.

PMID- 11329640
TI  - Reporting client violence.
AB  - Much has been written about client violence against social workers; however,
      little attention has been given to reporting behavior of social workers who have
      been the target of such violence. The study discussed in this article documents
      the prevalence of client violence among a sample of social workers from a broad
      range of social work settings. It examines respondents' reasons for not reporting
      or for reporting client violence to management. A random sample of 300 social
      workers was mailed a questionnaire that examined these issues. A total of 171
      questionnaires were returned, for a response rate of 57 percent. The majority of
      respondents had experienced some form of violence from clients. Approximately one
      quarter of respondents indicated that they did not report an incident of violence
      perpetrated against them by a client.

PMID- 11329641
TI  - Crimes against people with mental illness: types, perpetrators, and influencing
      factors.
AB  - The current emphasis on studying why people with severe mental illness are
      potentially violent has overlooked the effect of violence committed against these
      individuals. To balance the understanding of the person-in-environment
      conceptualization of severe mental illness, the nature, scope, and effect of
      crime and victimization should be examined as part of the context in which these
      individuals live and function. The study reported in this article examined the
      nature and scope of victimization as experienced by 234 individuals with a
      diagnosed major mental illness; what types of victimization experiences occurred
      during their lifetime; what specific victimization experiences these individuals
      identified as the most troubling; who the perpetrators for these specific
      victimization experiences were; and what influence demographic and clinical
      characteristics played in influencing the risk of victimization among this group.
      The study indicates that social workers should better assess for experiences of
      victimization among people with mental illness and better understand the effect
      of such experiences on the individual's symptoms and day-to-day functioning.

PMID- 11329642
TI  - Improving pregnancy outcome during imprisonment: a model residential care
      program.
AB  - The female prison population has increased dramatically in recent years. Most
      women prisoners are involved with drugs, and as many as 25 percent are pregnant
      or have delivered within the past year. Reproductive health and drug treatment
      services for women in prison are inadequate, if they are available at all, and
      although illicit drugs are readily available in prison, drug-involved pregnant
      women often are incarcerated to protect fetal health. Studies of pregnancy
      outcome among women prisoners have demonstrated high rates of perinatal mortality
      and morbidity. This article examines issues related to pregnancy among women
      prisoners and describes an innovative residential program designed for pregnant,
      drug-dependent women in a state adult corrections system. Social workers can play
      an important role in promoting policy reform and improved services for this
      underserved population.

PMID- 11329643
TI  - Survivors of childhood abuse: their reported experiences with professional help.
AB  - This article analyzes the self-reports of 384 adults who responded to a survey of
      people abused physically, sexually, or emotionally by family members in
      childhood. Most of the respondents sought help as adults from social workers and
      other mental health professionals for the long-term effects of their abusive
      experiences. This article analyses the reports of their help-seeking experiences
      against a backdrop of the reports of clinicians and researchers on working with
      survivors, as reported in the literature. Although survivors of childhood abuse
      often are described as having difficulty relating to professionals, these
      respondents persisted in seeking help and tended to report at least one
      experience with professional services that was very helpful. Their self-esteem
      and family functioning in adulthood was associated with having had a very helpful
      professional or service provider. The findings describe the responses most valued
      by survivors, as well as their views of the limitations of available services.

PMID- 11329644
TI  - Gay and lesbian adoptive and foster care placements: can they meet the needs of
      waiting children?
AB  - Although the number of children in need of adoptive homes is growing, the number
      of prospective adoptive parents is decreasing. On the basis of an extensive
      review of relevant literature, the present study explored a potentially viable
      although controversial and little-researched option for increasing the pool of
      prospective parents: adoptions by gay men and lesbians. Data for this study were
      collected from child welfare workers and gay and lesbian adoptive and foster
      parents. A content analysis of the data suggests that gay men and lesbians
      experience considerable and seemingly unjustified obstacles in their efforts to
      become adoptive and foster parents. Major implications for practice and policy
      are offered, as are future directions for research.

PMID- 11329645
TI  - Challenges of parenting for families living with HIV/AIDS.
AB  - Given the continual rise of HIV infection in our communities and the improved
      life span for many who are HIV-positive, social workers in all fields of practice
      have clients whose lives have been touched by HIV/AIDS. This article reviews
      relevant literature and reports on the parenting needs that emerged in a Canadian
      study that examined the experiences of 105 mothers and fathers living with
      HIV/AIDS. The majority of the children in the study were not HIV-positive. Some
      themes related to parenting in the literature, and evident in this study, were
      chronic sorrow, stress and burden, normalization, stigma, secrecy, and
      disclosure. In the study parenting was found to be a source of joy and an
      additional challenge in an already complicated life. Important new themes were
      family life as precious time, focused parenting, the different effects of
      HIV/AIDS, the parenting preparation needs of fathers, and the efforts to parent
      affected and infected children differently. Parenting when living with HIV/AIDS
      requires attention from clinicians and researchers in a range of settings.

PMID- 11329646
TI  - Effect of a changing health care environment on social work leaders: obstacles
      and opportunities in hospital social work.
AB  - The health care system is undergoing dramatic change in auspice, structure, and
      services delivery in response to an emphasis on market-driven, cost-containment
      strategies. Consequently, many hospital social work directors either have lost
      some of their administrative responsibilities or have expanded their span of
      control beyond social work services. This article examines the responses of
      social work administrators to the breadth of changes occurring throughout their
      hospitals; the major accomplishments of social work services within their
      facilities; and the failures, frustrations, and obstacles in the delivery of
      social work services. As a result of examining the relationship between their
      actual and anticipated behavior and changes in the hospital and external
      environment, the authors found that social work leaders in hospitals understand
      the complexities and challenges of the world around them. Overall, they have
      exhibited commitment, competence, and confidence in shaping organizational
      change.

PMID- 11329647
TI  - The diagnostic strengths manual?.

PMID- 11329648
TI  - Speciesism?.

PMID- 11329649
TI  - Speciesism?.

PMID- 11329650
TI  - Reflections on empowerment-based practice..

PMID- 11329651
TI  - Prison memoir.

PMID- 11329652
TI  - Reducing welfare benefits .

PMID- 11329653
TI  - Imaging of suspected acute small bowel obstruction.

PMID- 11329654
TI  - Computed tomography evaluation of intestinal ischemia.

PMID- 11329655
TI  - Inflammatory conditions of the colon.

PMID- 11329656
TI  - Ultrasonography and computed tomography of appendicitis and diverticulitis.

PMID- 11329657
TI  - Acute aortic abnormalities.
AB  - Aneurysm and type B dissections account for most acute abdominal aortic
      abnormalities. The postsurgical aorta deserves special attention owing to the
      risk of complications. Most aortic abnormalities presenting acutely are
      emergencies that carry a high risk of mortality, and imaging plays a critical
      role in patient evaluation. Modern helical CT scanners provide excellent spatial
      resolution, are readily available, and allow for rapid imaging. For these
      reasons, helical CT angiography is the imaging modality of choice for initial
      evaluation of the acute aorta.

PMID- 11329658
TI  - Imaging acute obstetric and gynecologic abnormalities.

PMID- 11329659
TI  - Case of the season. Emphysematous cholecystitis.

PMID- 11329660
TI  - Imaging the patient with right upper quadrant pain.
AB  - A variety of high-resolution imaging techniques are currently available for the
      evaluation of patients with RUQ pain. In these patients, an imaging approach that
      is based on identifying the presence of certain clinical signs and symptoms can
      aid in choosing the appropriate imaging modality and establishing the diagnosis.
      For patients presenting with a positive Murphy sign, sonography and biliary
      scintigraphy are the most useful initial imaging techniques. In patients with
      fever and a negative Murphy sign, a combination of sonography and contrast
      enhanced CT can establish the diagnosis in most cases. And finally, in patients
      without fever or a positive Murphy sign, CT and MR are appropriate first-line
      imaging techniques.

PMID- 11329661
TI  - Computed tomography evaluation of acute pancreatitis.

PMID- 11329662
TI  - Computed tomography and ultrasonography of acute renal abnormalities.

PMID- 11329663
TI  - Method for measuring mutagen formation potential (MFP) on chlorination as a new
      water quality index.
AB  - A novel water quality index, the mutagen formation potential (MFP) is proposed
      for use in evaluation of the quality of drinking water which may contain
      pollutants capable of forming mutagens when chlorinated under the conditions used
      in water purification processes. A method for measuring MFP was established as
      follows. The water sample to be tested is diluted until the TOC reaches 3-4 mg l
      1, the pH is adjusted to 7.0 +/- 0.2, sodium hypochlorite is added to obtain
      conditions where Cl/TOC = 3-4 mg Cl (mg C)-1, and the water sample is left
      standing for 24 +/- 2 h at room temperature. Thereafter, 21 of the chlorinated
      water sample at pH 2.0 +/- 0.1 is passed through a Sep-Pak Plus CSP-800 cartridge
      to adsorb any mutagens formed, and DMSO is applied to the cartridge to desorb the
      mutagens. Then, a 2 ml sample of the eluate is collected after the DMSO had begun
      to flow out of the cartridge and evaluated by the Ames Salmonella mutagenicity
      assay (preincubation method).

PMID- 11329664
TI  - Microbially available organic carbon, phosphorus, and microbial growth in
      ozonated drinking water.
AB  - Ozonation is a disinfection technique commonly used in the treatment of drinking
      water. It destroys harmful microbes, but it also degrades organic matter in
      water, increasing the bioavailability of organic matter. Recently, it was found
      that not only organic carbon but also phosphorus can limit the microbial growth
      in drinking water, which contains high amount of organic matter. We used a
      bioassay to analyze whether ozone could also increase the microbially available
      phosphorus (MAP) in drinking water, and whether MAP in ozone-treated water was
      associated with the growth of heterotrophic microbes. We found that both
      assimilable organic carbon and MAP concentrations were increased by ozone
      treatment. In ozonated water, microbial growth was mainly limited by phosphorus,
      and even minor changes in MAP concentration dramatically increased the growth
      potential of heterotrophic microbes. In this study, ozonation increased the MAP
      by 0.08-0.73 microgram P/l, resulting in an increase of 80,000-730,000 CFU/ml in
      water samples. In contrast to MAP, the content of assimilable organic carbon
      (AOCpotential) did not correlate with microbial growth. The results show that in
      water treatment not only AOCpotential but also MAP should be considered as an
      important factor that can limit microbial growth in drinking water.

PMID- 11329665
TI  - Development of a nested-PCR assay for the detection of Cryptosporidium parvum in
      finished water.
AB  - A nested-PCR assay, incorporating an internal positive control, was developed for
      Cryptosporidium monitoring in finished water. This assay was capable of
      reproducibly detecting 8 oocysts in spiked-filtered water samples collected from
      5 South Australian water treatment plants. The RT-PCR assay of Kaucner and
      Stinear (Appl. Environ. Microbiol. 64(5) (1998) 1743) was also evaluated for the
      detection of Cryptosporidium parvum. Initially, under our experimental
      conditions, a detection level of 27 oocysts was achieved for spiked reagent water
      samples. This level was improved to 5 oocysts by modification of the method.
      Untreated South Australian source waters concentrated by calcium carbonate
      flocculation were found to be highly inhibitory to the RT-PCR assay.
      Concentration of similar samples using Envirochek filters appeared to eliminate
      PCR inhibition. While both methods possessed similar sensitivities the nested-PCR
      assay was more reproducible, more cost effective, simpler to perform and could
      detect both viable and non-viable intact Cryptosporidium parvum oocysts, which is
      an important consideration for plant operators. These factors make the nested-PCR
      assay the method of choice for screening large numbers of potable water samples,
      where a reliable low level of detection is essential.

PMID- 11329666
TI  - Comparison of methods for determination of microbial biomass in wastewater.
AB  - Microbial biomass in wastewater was determined by methods used in environmental
      microbiology and by a method used in wastewater engineering based on a conceptual
      model simulating fundamental microbial processes in wastewater from measured
      oxygen uptake rates. The methods originating from environmental microbiology are
      based on staining and counting of cells for the determination of total cell
      biomass (acridine orange and DAPI), physiological state of cells (LIVE/DEAD
      BacLight) and activity of cells (reduction of the redox dye CTC and
      microautoradiography). Depending on the staining method applied, cell biomasses
      yielded 15-86% of the biomass defined by the model, and good correlations between
      cell biomass and model biomass were found. Cell biomass, oxygen uptake and
      acetate uptake were measured in wastewater, where acetate was added. Substrate
      uptake rates were found not to be proportional to the increases in cell biomass,
      suggesting that only a small fraction of the cell biomass was responsible for the
      main part of the substrate uptake. Despite the differences found between cell
      biomass and model biomass, it was recommended to use the conceptual model as an
      engineering tool for simulation of microbial processes and wastewater quality
      changes. However, there should be a clear distinction between the terms 'model
      biomass', 'cell biomass' and different activity measurements of cells.

PMID- 11329667
TI  - Arsenic removal during conventional aluminium-based drinking-water treatment.
AB  - The changing forms and concentrations of arsenic through aluminium-based
      coagulation treatment processes were tracked for three drinking-water treatment
      plants. This has provided direct evidence of where and how arsenic is removed. In
      general, soluble As(V) is converted to particulate As(V) by adsorption during
      rapid mixing, and is removed along with naturally occurring particulate arsenic
      predominantly by clarification. Soluble As(III) tracks through the treatment
      processes and is converted to soluble As(V) during final chlorination. The
      ability of a water treatment process to achieve the maximum acceptable
      concentration for arsenic in drinking water is dependent on the concentration of
      As(III) in the source water.

PMID- 11329668
TI  - Aerobic biodegradation of an oxygenates mixture: ETBE, MTBE and TAME in an upflow
      fixed-bed reactor.
AB  - Aerobic degradation of ethyl tert-butyl ether (ETBE), Methyl tert-butyl ether
      (MTBE) and tert-amyl methyl ether (TAME), as tertiary-substrates, was studied in
      a continuous upflow fixed-bed reactor (UFBR) using an external oxygenator and
      sintered glass rings as biomass carriers. The UFBR has been shown to be an
      effective system for the simultaneous and continuous long-term degradation of the
      three-oxygenates mixture as sole source of carbon and energy. Therefore, the
      oxygenates feed concentration must be related in conjunction with the hydraulic
      retention time "HRT" and vice versa. The permissible feed concentration of both
      MTBE and TAME to achieve more than 99% removal efficiency is about 80 mg L-1 at a
      constant HRT of 24 h. The same performance can be obtained if the HRT kept at a
      value equal or above to 15 h for a feed concentration of about 80 mg L-1 of both
      MTBE and TAME. However, the ETBE removal efficiency was always greater than 99%
      whatever the ETBE concentration feed (between 10 and 100 mg L-1 at a constant HRT
      of 24 h) and the HRT (between 24 and 13 h at a constant concentration feed of
      about 80 mg L-1) tested in this study. The highest ETBE, MTBE and TAME removal
      rates achieved throughout the UFBR runs, with efficiency better than 99%, were
      140 +/- 5, 132 +/- 2 and 135 +/- 2 mg L-1 d-1, respectively. No metabolic
      intermediates including tert-butyl alcohol (TBA), tert-butyl formate (TBF) and
      tert-amyl alcohol (TAA) were detected in the effluent during all the reactor
      runs. Furthermore, based on the chemical oxygen demand balance, all the removed
      oxygenates were completely metabolized. The results of this study suggest that
      the higher resistance to biodegradation exhibited by the MTBE and the TAME is
      probably due to the steric hindrance for the attacking enzyme(s); and the major
      limiting step to the oxygenate degradation maybe the accessibility and the
      cleavage of the ether bond, but not the assimilation of their major metabolites
      such as TBA, TBF and TAA. These results were concomitant with the batch tests
      using the reactor's immobilized biomass as inoculum.

PMID- 11329669
TI  - A mathematical model of a shallow and eutrophic lake (the Keszthely Basin, Lake
      Balaton) and simulation of restorative manipulations.
AB  - Concern about the overall management of lakes has been growing, and a lake
      ecological model provides the guidelines necessary for such management. In this
      study, an ecological model describing the ecosystem of the Keszthely Basin, Lake
      Balaton, Hungary, one of the typical shallow and eutrophic lakes, was proposed.
      This model includes three types of zooplankton and two types of fish as well as
      two types of algae and nutrients. Parameters concerning the algae and fish were
      estimated based on observations in the basin between 1991 and 1995. The other
      parameters and the structure of the model were determined by our previous study.
      The parameters of the model were calibrated with the Monte Carlo technique, and
      its predictability was confirmed. The effects on the basin's ecosystem of three
      restorative manipulations, namely a biomanipulation, reduction of loading
      phosphorus, and dredging the sediment, were assessed by simulation studies using
      the proposed model. The simulation results indicated that a biomanipulation that
      removed 90% of the bream should suppress the growth of algae temporarily through
      bottom-up regulation; however, this effect seemed to not be perpetuated in this
      basin. The reduction of loading phosphorus seemed to be the most effective means
      to suppress algal growth, while dredging of sediment seemed to be the most
      desirable restoration method from the standpoint of the overall management of the
      lake, because it was expected to accelerate the growth of fish population as well
      as to suppress algal growth. Furthermore, the algal growth suppression mechanism
      of the dredging was discussed on the basis of the model calculations.

PMID- 11329670
TI  - Influence of peat on Fenton oxidation.
AB  - A diagnostic probe was used to estimate the activity of Fenton-derived hydroxyl
      radicals (.OH), reaction kinetics, and oxidation efficiency in batch suspensions
      comprised of silica sand, crushed goethite (alpha-FeOOH) ore, peat, and H2O2
      (0.13 mM). A simple method of kinetic analysis is presented and used to estimate
      the rate of .OH production (POH) and scavenging term (ks), which were used to
      establish the influence of organic matter (Pahokee peat) in Fenton systems. POH
      was greater in the peat-amended systems than in the unamended control, and ks was
      approximately the same. Any increase in scavenging of .OH that resulted from the
      addition of peat was insignificant in comparison to radical scavenging by
      reaction with H2O2. Also, treatment efficiency, defined as the ratio of probe
      conversion to H2O2 consumption over the same period was greater in the peat
      amended system. Results suggest that .OH production is enhanced in the presence
      of peat by one or more peat-dependent mechanisms. Fe concentration and
      availability in the peat, reduction of Fe(III) to Fe(II) by the organic matter,
      and reduction of organic-complexed Fe(III) to Fe(II) are discussed in the context
      of the Fenton mechanism.

PMID- 11329671
TI  - By-products formation during degradation of isoproturon in aqueous solution. I:
      Ozonation.
AB  - The degradation of the herbicide isoproturon during its ozonation in aqueous
      solution has been investigated with the aim of identifying intermediate as well
      as final by-products formed. At ambient temperature, phosphate-buffered (pH = 7)
      isoproturon aqueous solutions (10, 10(-1) and 10(-3) mg/l) were ozonated in a
      semi-batch reactor, under a continuous flow of ozonated air whose ozone
      concentration was 9 and 0.9 mg O3/lair for the highest and the two lower
      herbicide concentrations respectively. Measured steady-state ozone concentrations
      during the two sets of experiments (i.e. the highest and the lower isoproturon
      concentration) were 1.9 and 0.7 mg O3/l. Under all of the above conditions,
      isoproturon was always completely removed in a period ranging between 5 and 15
      min, essentially by reacting with molecular ozone. High-performance liquid
      chromatography-mass spectrometry (HPLC-MS) analyses indicate that primary
      degradation by-products are formed either by introducing OH groups in the
      aromatic ring and/or in the side-chain substituents, or by breaking down the
      isopropyl alkyl chain. The results also show that these primary intermediates are
      successively degraded yielding low molecular weight compounds such as aldehydes,
      simple organic acids and alpha-oxo-acids, which have been identified by gas
      chromatography-electron capture detection (GC-ECD), ion chromatography (IC) and
      GC-MS, respectively. On the basis of the analytical results, a pathway for the
      degradation of isoproturon by ozone has been proposed.

PMID- 11329672
TI  - By-products formation during degradation of isoproturon in aqueous solution. II:
      Chlorination.
AB  - After a previous study in which the considered oxidant was ozone (Part I), a
      laboratory investigation has been carried out to study the degradation of the
      herbicide isoproturon during its reaction with another oxidant, i.e. chlorine, in
      aqueous solution (Part II; this paper). The specific aim was to identify the by
      products formed. The effects of pH and the presence of bromide ions were studied.
      Reactions have been carried out at room temperature, in phosphate buffered
      aqueous solutions, at four pHs (6, 7, 8 and 9). By-products identification was
      first performed using relatively high initial reagent concentrations which were
      analytically convenient ([isoproturon] = 40 mg/l, [HClO + ClO-] = 160 mg Cl/l,
      [Br-] = 80 mg/l). In follow-up studies, the by-products identified during this
      preliminary step were searched for when using concentration values closer to
      those actually encountered at real water treatment plants ([isoproturon] = 0.4
      and 0.004 mg/l, [HClO + ClO-] = 1.6 mg Cl/l, [Br-] = 0.8 and 0.008 mg/l). Under
      all of the studied conditions, the results showed that isoproturon is completely
      degraded and that it decays much faster in the presence of bromide. The pH has a
      negligible influence when bromide ions are absent. On the contrary, if bromide
      ions are present, the isoproturon decay is slower at higher pH values. High
      performance liquid chromatography-mass spectrometry (HPLC-MS) analyses have led
      to the identification of several by-products as a result of simultaneous
      oxidation and substitution reactions, both occurring on the aromatic ring of the
      herbicide. However, the more abundant by-products are those resulting from the
      oxidation of the isoproturon aromatic ring. As far as halogenated by-products are
      concerned, the higher the bromide ion concentration the higher the ratio of
      brominated to chlorinated by-products. On the basis of the analytical results, a
      pathway for isoproturon degradation under the studied conditions is proposed.

PMID- 11329673
TI  - Simultaneous carbon and nitrogen removal from high strength domestic wastewater
      in an aerobic RBC biofilm.
AB  - High strength domestic wastewater discharges after no/partial treatment through
      sewage treatment plants or septic tank seepage field systems have resulted in a
      large build-up of groundwater nitrates in Rajasthan, India. The groundwater table
      is very deep and nitrate concentrations of 500-750 mg/l (113-169 as NO3(-)-N) are
      commonly found. A novel biofilm in a 3-stage lab-scale rotating biological
      contactor (RBC) was developed by the incorporation of a sulphur oxidising
      bacterium Thiosphaera pantotropha which exhibited high simultaneous removal of
      carbon and nitrogen in fully aerobic conditions. T. pantotropha has been shown to
      be capable of simultaneous heterotrophic nitrification and aerobic
      denitrification thereby helping the steps of carbon oxidation, nitrification and
      denitrification to be carried out concurrently. The first stage having T.
      pantotropha dominated biofilm showed high carbon and NH4(+)-N removal rates of
      8.7-25.9 g COD/m2 d and 0.81-1.85 g N/m2 d for the corresponding loadings of 10.0
      32.0 g COD/m2 d and 1.0-3.35 g N/m2 d. The ratio of carbon removed to nitrogen
      removed was close to 12.0. The nitrification rate increased from 0.81 to 1.8 g
      N/m2 d with the increasing nitrogen loading rates despite a high simultaneous
      organic loading rate. However, it fell to 1.53 g N/m2 d at a high load of 3.35 g
      N/m2 d and 32 g COD/m2 d showing a possible inhibition of the process. A
      simultaneous 44-63% removal of nitrogen was also achieved without any significant
      NO2(-)-N or NO3(-)-N build-up. The second and third stages, almost devoid of any
      organic carbon, acted only as autotrophic nitrification units, converting the
      NH4(+)-N from stage 1 to nitrite and nitrate. Such a system would not need a
      separate carbon oxidation step to increase nitrification rates and no external
      carbon source for denitrification. The alkalinity compensation during
      denitrification for that destroyed in nitrification may also result in a high
      economy.

PMID- 11329674
TI  - Variation of bulk properties of anaerobic granules with wastewater type.
AB  - Development of a granular sludge with high strength, high biological activity and
      a narrow settling distribution is necessary for optimal operation of high-rate
      upflow anaerobic treatment systems. Several studies have compared granules
      produced from different wastewaters but these have largely been from laboratory
      fed reactors or compared granules from full-scale reactors fed similar wastewater
      types. Though two authors have commented on the inferiority of granules produced
      by a protein-based feed, the properties of these granules have not been
      characterised. In this paper, granules from full-scale reactors treating fruit
      and vegetable cannery effluent, two brewery effluents and a pig abattoir
      (slaughterhouse) were compared in terms of basic composition, size distribution,
      density, settling velocity, shear strength, and EPS content. The results
      supported previous qualitative observations by other researchers that indicate
      granule properties depend more on wastewater type rather than reactor design or
      operating conditions such as pre-acidification level. The cannery-fed granules
      had excellent shear strength, settling distribution and density. Granules from
      the two brewery-fed reactors had statistically the same bulk properties, which
      were still acceptable for upflow applications. The protein-grown granule had poor
      strength and settling velocity.

PMID- 11329675
TI  - The formation of malodorous dimethyl oligosulphides in treated groundwater: the
      role of biofilms and potential precursors.
AB  - Water distributed from the Wanneroo Groundwater Treatment Plant intermittently
      contains dimethyl trisulphide (DMTS). The compound is responsible for a "swampy
      odour" in the water. DMTS production from potential precursors was insignificant
      in the absence of biofilms when compared with DMTS production from precursors in
      the presence of biofilms in a biofilm reactor. Greatest dimethyl disulphide
      (DMDS) and DMTS production (> 3000 ng L-1 DMTS) occurred in the reactors when
      supplied with methane thio-containing compounds, such as methionine, S-methyl
      cysteine and methyl-3-(methylmercapto)-propionate. Abiotic DMTS production from
      oligosulphides also occurred through the addition of the methylating agents,
      methyl iodide or methyl-p-toluene sulphonate. Significant DMTS production also
      occurred with Wanneroo water that contained added omega-thio-containing compounds
      such as cysteine (1400 ng L-1 DMTS), and 3-mercaptopropionate (210 ng L-1).
      Biomethylation, a ubiquitous response by microorganisms for the detoxification of
      toxic compounds, generated DMDS/TS from biofilm oligosulphides. Biofilms exposed
      to the toxic compounds selenate or 2,4,6-trichlorophenol methylated
      oligosulphides in addition to the toxins. Sodium sulphide also stimulated DMTS
      production. Easily Biodegradable Dissolved Organic Carbon (BDOC) probably
      contributed indirectly to DMTS production by the biofilms, although whether this
      was a result of its stimulation of greater microbial activity or consumption of
      oxygen, or both, remains unresolved. Stagnation of water in the biofilm reactors
      also increased DMTS production, which was concomitant with depletion of oxygen
      concentrations in the bulk water. Many processes, such as degradation of methane
      thio-containing compounds, methylation of sulphides and oligosulphides, and
      changes in contributions of different metabolic pathways upon depletion of oxygen
      concentrations upon water stagnation, probably contribute simultaneously to
      "swampy odour" production in the distribution system.

PMID- 11329676
TI  - Development of anaerobic migrating blanket reactor (AMBR), a novel anaerobic
      treatment system.
AB  - A novel anaerobic treatment system, the anaerobic migrating blanket reactor
      (AMBR), was developed after completing a parallel study with upflow anaerobic
      sludge blanket (UASB) and anaerobic sequencing batch reactor (ASBR) processes.
      Using sucrose as the main component of a synthetic wastewater, the AMBR achieved
      a maximum chemical oxygen demand (COD) loading rate of 30 g.l-1.day-1 at a 12-h
      hydraulic retention time (HRT). This resulted in a standard methane production
      rate (SMPR) of 6.51.l-1.day-1 and an average methane-based COD (MCOD) removal
      efficiency of 62.2%. A key element in granular biomass formation was migration of
      the biomass blanket through the reactor. Although a carbohydrate-rich wastewater
      was used, no separate pre-acidification was required for the AMBR, because of
      high mixing intensities and wash out of acidogenic bacteria. In contrast, the
      absence of pre-acidification created "bulking" problems (caused by abundant
      acidogenic bacteria at the surface of granules) in a UASB reactor, operated under
      conditions similar to that of the AMBR. As a result, a maximum COD loading rate
      and SMPR of 21 g.l-1.day-1 and 4.91.l-1.day-1 were achieved, respectively, for
      the UASB reactor at a 12-h HRT. These values were 18 g.l-1.day-1 and 3.71.l-1.day
      1, respectively, for an ASBR at a 12-h HRT. Hence, the performance of the AMBR in
      treating a carbohydrate-rich wastewater was found to be superior in terms of
      maximum loading rate and SMPR.

PMID- 11329677
TI  - NUR and our relationship in BNR processes with sewage at different temperatures
      and its design application.
AB  - Denitrification is known as an essential part of a biological nutrient removal
      (BNR) process to remove nitrogen and it also affects phosphorus removal. However,
      an accurate prediction of nitrogen removal is extremely difficult because there
      are too many factors involved. This study was conducted to find a relationship
      between nitrate uptake rate (NUR) and carbonaceous oxygen uptake rate (OUR) and
      develop a simple method to predict applicable NUR for the design of various BNR
      processes. Sewage was subdivided into soluble and particulate organic fractions.
      NUR/OUR ratios were measured by respirometer with these organic fractions and the
      test sludges grown at various BNR processes and temperatures. NUR/OUR ratios were
      varied with the types of organic fractions of sewage and temperature. The NURs
      predicted from the NUR/OUR ratios and computed OUR based on the total tank volume
      of anoxic and oxic stages with the influent sewage characteristics were very much
      comparable with the observed NURs from various BNR processes.

PMID- 11329678
TI  - Soft deposits, the key site for microbial growth in drinking water distribution
      networks.
AB  - In this project we studied the microbiological quality of soft pipeline deposits
      removed from drinking water distribution networks during mechanical cleaning.
      Drinking water and deposit samples were collected from 16 drinking water
      distribution networks located at eight towns in different parts of Finland. Soft
      pipeline deposits were found to be the key site for microbial growth in the
      distribution networks. The microbial numbers in the soft deposits were
      significantly higher than numbers in running water. The highest microbial numbers
      were detected in the main deposit pushed ahead by the first swab. The deposits
      contained high numbers of heterotrophic bacteria, actinomycetes and fungi. Also
      coliform bacteria were often isolated from deposit samples. Manganese and copper
      in the deposits correlated negatively with the numbers of heterotrophic bacteria.
      After a year, the viable microbial numbers in the new deposits were almost as
      high as in the old deposits before the first mechanical cleaning. The bacterial
      biomass production was higher in the new than in the old deposits.

PMID- 11329679
TI  - Monochloramine decay in model and distribution system waters.
AB  - Chloramines have long been used to provide a disinfecting residual in
      distribution systems where it is difficult to maintain a free chlorine residual
      or where disinfection by-product (DBP) formation is of concern. While chloramines
      are generally considered less reactive than free chlorine, they are inherently
      unstable even in the absence of reactive substances. These reactions, often
      referred to as "auto-decomposition", always occur and hence define the maximum
      stability of monochloramine in water. The effect of additional reactive material
      must be measured relative to this basic loss process. A thorough understanding of
      the auto-decomposition reactions is fundamental to the development of mechanisms
      that account for reactions with additional substances and to the ultimate
      formation of DBPs. A kinetic model describing auto-decomposition was recently
      developed. This model is based on studies of isolated individual reactions and on
      observations of the reactive ammonia-chlorine system as a whole. The work
      presented here validates and extends this model for use in waters typical of
      those encountered in distribution systems and under realistic chloramination
      conditions. The effect of carbonate and temperature on auto-decomposition is
      discussed. The influence of bromide and nitrite at representative monochloramine
      concentrations is also examined, and additional reactions to account for their
      influence on monochloramine decay are presented to demonstrate the ability of the
      model to incorporate inorganic demand pathways that occur parallel to auto
      decomposition.

PMID- 11329680
TI  - A flow injection-fluorometric method for the determination of ammonium in fresh
      and saline waters with a view to in situ analyses.
AB  - A version of the orthophthaldialdehyde-fluorescence ammonium determination for
      flow injection analysis (FIA) is presented here, with a view to its use for in
      situ, low-power consumption systems. Thus, the reaction temperature was limited
      to 30 degrees C and FIA was used in stop-flow mode (3 min stop). The calibration
      is linear up to 50 mumol l-1, but concentrations up to 100 mumol l-1 can be
      measured. Repeatability is around 1% in the range of 0.5-4 mumol l-1 and the
      detection limit is about 0.03 mumol l-1. Over the salinity range of 5-35
      (seawater practical salinity scale) the salt effect is almost negligible (within
      +/- 2%); and below salinity of 5 it increases to a maximum of -9% in fresh water
      compared to seawater. Hydrogen carbonate, dissolved oxygen and turbidity (either
      suspended sediments or phytoplankton cells) have almost no adverse effect in a
      wide range of concentrations, covering most natural water conditions. Relative
      interference of primary amines is negligible and mercury (a common sample
      preservative) does not depress the signal up to 20 mg l-1 Hg II. Sulfide, that
      may be present in areas with anoxic waters, depresses the signal only slightly
      and linearly (-9% at 100 mumol l-1 S2-). The method appears to be convenient for
      the determination of ammonium in most coastal, estuarine and fresh waters. Sample
      throughput is 9 h-1. The performance of the method can be improved, either by
      increasing the reaction time (low throughput) or, if enough energy is available,
      by increasing the reaction temperature (non-stop-flow mode, high throughput).
      Combining FIA and fluorometry appears to be interesting for in situ determination
      (submersible devices) of dissolved compounds in environments with variable
      salinity and turbidity (especially coastal and estuarine waters).

PMID- 11329681
TI  - Evaluation of 4-nonylphenols and 4-tert-octylphenol contamination of fish in
      rivers by laboratory accumulation and excretion experiments.
AB  - Laboratory accumulation and excretion experiments of 4-nonylphenols (NP) and 4
      tert-octylphenol (OP) were performed for killifish (Oryzias latipes). The
      bioconcentration factors (BCF, wet weight) in the whole fish were mean +/- SD of
      167 +/- 23 (n = 4) for NP and 261 +/- 62 (n = 4) for OP. The biological half
      lives in the whole fish were 9.9 h for NP and 7.7 h for OP. Parallel to the
      laboratory experiments, field survey on the chemicals contamination for water and
      ayu fish (Plecoglossus altivelis) from rivers flowing into Lake Biwa was
      performed. The contamination was not so high in agreement with the laboratory
      experimental data and the field BCF values (wet weight) in the ayu fish were 21
      +/- 15 (n = 8) for NP and 297 +/- 194 (n = 3) for OP.

PMID- 11329682
TI  - Interaction between Hg(II) and natural dissolved organic matter: a fluorescence
      spectroscopy based study.
AB  - Interaction between Hg(II) and dissolved organic matter (DOM) collected from
      surface water samples of the Florida Everglades was studied using different
      fluorescence spectroscopic methods. Complexation between Hg(II) and DOM leached
      from mangrove leaves, sawgrass, and periphyton was investigated. Both
      fluorescence emission and synchronous fluorescence spectra showed that these
      dissolved organic materials, whether they are highly degraded or are freshly
      leached, can "complex" Hg(II) since fluorescence intensity was quenched upon
      addition of Hg(II) to the DOM samples. Synchronous fluorescence spectra disclosed
      structural information on the DOM sample, regarding possible binding sites for
      Hg(II). Chemical parameters on the complexation of Hg(II), including the
      conditional stability constants and the percentage of fluorophores participating
      in the complexation, were estimated by the modified Stern-Volmer equation. A
      detailed investigation under different experimental conditions showed that the
      complexation of the DOM samples collected from the Everglades was influenced by
      pH, Cl-(aq) anion, and cations such as Ca2+ and Mg2+. Experimental results
      suggest that DOM-Hg(II) complexes can be removed from the water column through
      adsorption on biogenically precipitated CaCO3(s).

PMID- 11329683
TI  - Anaerobic codigestion of municipal solid waste and biosolids under various mixing
      conditions--I. Digester performance.
AB  - The feasibility of codigestion of the organic fraction of municipal solid waste,
      primary sludge, and waste activated sludge was evaluated in mesophilic (37
      degrees C), laboratory-scale digesters. In a first experiment, different startup
      strategies were compared using four digesters, operated under continuously mixed
      conditions. After two weeks, the experiment was continued under minimally mixed
      conditions. Results demonstrated that reducing the level of mixing improved
      digester performance. Therefore, in a second experiment, six digesters were
      operated to compare performance under continuous mixing and reduced mixing levels
      at various loading rates and solids levels. The continuously mixed digesters
      exhibited unstable performance at the higher loading rates, while the minimally
      mixed digesters performed well for all loading rates evaluated. In a third
      experiment, it was demonstrated that an unstable, continuously mixed digester was
      quickly stabilized by reducing the mixing level. These experiments confirmed that
      continuous mixing was not necessary for good performance and was inhibitory at
      higher loading rates. In addition, reduction of mixing levels may be used as an
      operational tool to stabilize unstable digesters.

PMID- 11329684
TI  - Anaerobic codigestion of municipal solid waste and biosolids under various mixing
      conditions--II: Microbial population dynamics.
AB  - Microbial population dynamics were evaluated in anaerobic codigesters treating
      municipal solid waste and sewage sludge. Ribosomal RNA based oligonucleotide
      probes were used to characterize changes in population abundance of syntrophic
      volatile fatty acid degrading bacteria and methanogens. Changes in community
      structure were linked to traditional performance parameters during the recovery
      of previously unstable codigesters induced by a reduction in mixing levels.
      Methanosarcina spp. were the most abundant aceticlastic methanogens in unstable
      codigesters with high acetate concentrations, while Methanosaeta concilii was
      dominant in stable systems with low levels of acetate. Growth of Syntrophobacter
      wolinii was enhanced during stabilization of a codigester with a well-developed
      population of Methanobacteriaceae, possibly because the presence of adequate
      numbers of these hydrogenotrophic methanogens encouraged the syntrophic oxidation
      of propionate. Mesophilic saturated fatty acid beta-oxidizing syntrophs were most
      abundant in previously unstable codigesters. One minimally mixed reactor became
      unstable after switching to continuously mixed conditions. After the switch,
      total archaeal abundance decreased sharply, though Methanobacteriaceae and
      Methanosarcina spp. levels increased as the fermentation became unbalanced. Based
      on the results presented here, mixing appears to inhibit the syntrophic oxidation
      of volatile fatty acids, possibly by disrupting the spatial juxtaposition of
      syntrophic bacteria and their methanogenic partners.

PMID- 11329685
TI  - Xanthomonas campestris strain selection for xanthan production from olive mill
      wastewaters.
AB  - Four Xanthomonas campestris strains were tested in olive mill wastewaters (OMW)
      for xanthan production. Differences among strains were found in the range of
      tolerance to OMW concentration and xanthan amount obtained. X. campestris NRRL B
      1459 S4LII was chosen by its capability for xanthan production from 50-60% OMW as
      the sole nutrient source.

PMID- 11329686
TI  - Hydrogen production in anaerobic reactors during shock loads--influence of
      formate production and H2 kinetics.
AB  - In this article the role of hydrogen as a process monitoring tool in methanogenic
      systems was studied by considering the influence of several key system
      parameters. Hydrogen production was found to be influenced mainly by the
      inocula's source pH, and varied only slightly with external pH and HCO3- levels.
      When an inoculum adapted to above neutral conditions (pH > 7) was shocked,
      reducing equivalents were selectively channelled through formate, while high
      hydrogen production was noticed with acidically (pH < 6.5) adapted inocula. The
      results also revealed that the production of hydrogen or formate during shock
      loads was not strongly associated with microbial morphology (granules or flocs)
      as high electron fluxes were possible through either during acidogenesis. Shock
      load experiments in continuous reactors revealed that neither hydrogen nor
      formate accumulated to any significant degree, nevertheless digester recovery
      took a long time due to the slow kinetics of volatile fatty acid degradation.
      Selective formate production under neutral pH environments, coupled with high
      hydrogenotrophic activity, was found to be responsible for the dampened hydrogen
      response during the early phases of gradually shocked systems (step change).
      Based on these results it appears that the role of hydrogen as a process
      monitoring tool has been overemphasised in the literature.

PMID- 11329687
TI  - BOD5 estimation for pulp and paper mill effluent using UV absorbance.
AB  - A novel method based on UV absorbance, is presented for estimating the BOD5 in
      pulp and paper mill effluent. This method could eventually be incorporated into
      an on-line sensor for BOD5 that is suitable for process control applications. Two
      streams, the reactor entrance and the final effluent, from two different mills
      were studied. One mill employed the Kraft pulping process, while the second mill
      was a thermo-mechanical one. The absorbance over the range 200-350 nm showed
      significant differences between the two mills. Because the two mills use very
      distinct processes, separate correlations were used to relate the absorbance to
      the BOD5 for both the mills. Results indicate that prediction of reactor entrance
      BOD5 was reasonable, whereas prediction of final effluent BOD5 was inaccurate,
      for both mills. Also studied was the effect of aeration on BOD5 results obtained
      at low BOD5 values for the Kraft mill.

PMID- 11329688
TI  - Color removal in groundwater through the enhanced softening process.
AB  - The source of water for Miami-Dade County, Florida is groundwater derived from
      the Biscayne aquifer. The raw water is rich in natural organic material producing
      correspondingly high color levels. Currently, breakpoint chlorination is used at
      the water treatment plant to control the color problem. However, this results in
      the formation of disinfection by-products. Proposed alternatives to reduce color
      and avoid by-product formation include the addition of coagulants such as ferric
      chloride and organic polymers, and the operation of the existing lime softening
      process at a higher pH. This study uses jar tests to evaluate the relative
      effectiveness of the proposed alternatives. Results indicate that significant
      color reduction is achieved using the existing lime softening process with
      activated silica coagulant by increasing the softening pH to 11 or more. Elevated
      pH also produced a > 30% reduction in total organic carbon. In the presence of
      higher raw water color (> or = 80 units), the addition of ferric chloride as
      coagulant at dosages of 80 mg/L is recommended.

PMID- 11329689
TI  - Algal growth inhibition effects and inducement modes by plant-producing phenols.
AB  - Evaluated here are the inhibitory effects on blue-green algae (Microcystis
      aeruginosa) produced by nine plant-producing phenols (caffeic, p-coumaric,
      ferulic, protocatechuic, sinapic, syringic, and vanillic acids, catechol, and
      hydroquinone), two plant-produced acids (quinic and shikimic acid), phenol,
      resorcinol, hydroxy hydroquinone, and phloroglucinol. Algal assays confirmed
      growth inhibition of M. aeruginosa by polyphenols, i.e., caffeic/protocatechuic
      acid, catechol, hydroquinone, hydroxy hydroquinone, and phloroglucinol, and by
      phenols containing methoxy groups, i.e., vanillic, sinapic, and syringic acids.
      Accordingly, this indicates good feasibility for controlling growth of M.
      aeruginosa using such plant-producing polyphenols and/or phenols as additives. A
      comparison of the inhibitory effects of the polyphenols showed that those induced
      by polyphenols in which phenolic hydroxy groups bound a benzene ring at ortho-
      and/or para-positions to another phenolic hydroxy group are stronger than the
      effects induced by polyphenols in which phenolic hydroxy groups are at only meta
      positions. Experiments showed that the only polyphenols demonstrating significant
      growth inhibition of M. aeruginosa were autoxidized. These results suggest that
      autoxidation of the polyphenols induces inhibitory effects by producing
      polyphenol-autoxidized products such as radicals.

PMID- 11329690
TI  - Allele-sharing among affected relatives: non-parametric methods for identifying
      genes.
AB  - Non-parametric linkage analysis examines similarities among affected relatives in
      alleles of one or more genetic markers (pieces of DNA at known locations on a
      chromosome). The objective is to evaluate departures from the null hypothesis
      that the markers are not near a disease gene. Under the null hypothesis, Mendel's
      laws give the probabilities that a set of relatives exhibits a particular allele
      sharing pattern, and the null hypothesis is rejected if the extent of allele
      sharing among affected relatives exceeds Mendelian expectation. Because the
      rationale for allele-sharing methods is intuitively plausible and easily grasped,
      geneticists have used these methods for more than 30 years, well before the
      advent of the large sets of polymorphic markers that have made linkage analysis
      so fruitful today. Here we describe methods for assessing whether the extent of
      marker allele sharing among affected relatives exceeds Mendelian expectation. We
      first quantify the notion of allele sharing and the probabilities of allele
      sharing in various sets of relatives. Then we describe allele sharing methods for
      affected sibs and more general sets of relatives. We also discuss related issues
      of test size and power. We conclude with a brief discussion of areas in need of
      further research.

PMID- 11329691
TI  - Genetic linkage methods for quantitative traits.
AB  - We discuss methods for detecting genetic linkage for quantitative data. The usual
      LOD score method uses a pseudolikelihood formulation and has optimal power
      provided all parameters are correctly specified, but can lead to erroneous
      estimates of the location for the locus influencing a trait under
      misspecification of parameters describing the variance of the trait. Alternative
      methods, in which attention focuses upon modelling covariation among relatives as
      a function of genetic marker, similarity lead to unbiased estimates of the
      location and major gene heritability of the trait influencing locus. The Haseman
      Elston approach uses a regression method to perform linkage analysis and its
      properties have been widely studied. This method is generally less powerful than
      variance components procedures, but the maximum likelihood-based variance
      components procedures require normality of the trait to ensure robustness of the
      genetic linkage tests (i.e. a correct false positive rate). When samples are non
      randomly selected an ascertainment correction is generally required in order to
      obtain unbiased parameter estimates when applying variance components methods.
      For quantitative traits, ascertainment corrections usually condition either on
      the proband exceeding a threshold, or on the trait value of the proband. We
      summarize simulations that show that both approaches lead to similar efficiencies
      for estimating genetic effects. Finally, we discuss methods for analysing
      diseases that include time-to-onset information. A variety of methods are
      available for the linkage analysis of quantitative traits. Here, we have reviewed
      the most commonly used methods.

PMID- 11329692
TI  - A chronology of fine-scale gene mapping by linkage disequilibrium.
AB  - The past decade produced several proposals for fine-scale gene mapping using
      linkage disequilibrium data. The suggested methods fall into two main groups,
      those that rely on pairwise statistics and those that rely on haplotypes. This
      paper reviews each strategy's development from a chronological perspective.

PMID- 11329693
TI  - Home safety.
AB  - There are more accidents in the home than many other environments, yet there is
      no duty on local authorities to promote domestic safety per se and the
      discretionary powers under the Home Safety Act 1961 are rarely used. The local
      authority remit in safe housing is therefore largely through housing enforcement
      and grant led activity. The main statutory controls available to local
      authorities in addressing home safety are found under various Housing Acts, in
      particular the statutory standard of fitness for habitation, which can provide
      remedy for some, although not all, potential home accidents. There are many
      potential hazards in the home which current legislation fails to address. This is
      one reason why a new standard of assessing domestic conditions--the Housing
      Health and Safety Rating System--is currently being considered. This new system
      seeks to change the current emphasis on a 'materials and construction
      specification' type approach to a system based on known domestic hazards and
      their reduction ('performance specification') although there remains much debate
      around the subject. This paper considers the current and proposed systems and
      other opportunities available to local authorities in addressing the major area
      of home safety.

PMID- 11329694
TI  - The distracted driver.
AB  - A serious health problem is developing from automobile collisions caused by
      distracted drivers. This is a result of the rapid proliferation of portable
      cellular telephones and personal organisers used while driving, the development
      of more sophisticated entertainment systems and instrument panel controls, the
      advent of navigation and television displays in vehicles and promises of
      sophisticated wireless e-mail, FAX and Internet services in the vehicle.
      Preoccupation with electronic gadgets may also degrade human driving performance.
      Many drivers however, sincerely believe they have the talent to do several things
      at the same time, such as hold and look at a cellular telephone in one hand and
      drive with a beverage container in the other hand whilst at the same time,
      exercise their personal skills. Obviously, they believe that they do not need two
      hands on the steering wheel and two eyes on the road. This is a unique situation
      requiring intensive health promotion as distracted or 'offensive driving' may be
      habit forming and difficult to change, any significant design remedies will be
      slow to arrive and may be circumvented, and the regulatory laws have proved
      difficult or impossible to enforce. This special need may require research to
      determine the most effective techniques for health promotion.

PMID- 11329695
TI  - Comfort and health in commercial aircraft: a literature review.
AB  - Air travel is becoming increasingly more accessible to people both through the
      availability of cheap flights and because the airlines are now able to cater for
      individuals of all ages and disabilities. The wide bodies of many new aircraft
      permit the airlines to have very flexible seating options. Airline operators
      currently have an important role in determining the comfort and spaciousness of
      the seating in their aircraft. Passengers who remain seated for the bulk of a
      flight may risk oedema or deep vein thrombosis. This could be particularly
      important for larger people in certain economy class seats. The absence of
      smoking on planes has encouraged designers to cut back on the rate of cabin
      ventilation and hence introduce filtered recirculated air to the aircraft cabin.
      In new planes the ventilation rate is under pilot control and savings (economies)
      can be achieved by using decreased ventilation. A lower ventilation rate may lead
      to 'less comfortable air quality' in some parts of the plane and an increased
      risk of possible cross-infection from other passengers on the flight.
      Technological advances in jet engine design has permitted larger passenger planes
      to fly longer distances and at greater altitudes than ever before. The higher
      flying altitude is associated with a lower cabin pressure, which has an important
      physiological effect on oxygen saturation in the blood of both crew and
      passengers, particularly for the very young, the elderly and those who are less
      fit.

PMID- 11329696
TI  - Personal exposure to benzene and the influence of attached and integral garages.
AB  - Benzene is an air pollutant that is a recognised human carcinogen. An air quality
      standard has been established for ambient air in the UK to reduce the
      population's exposure. It has been estimated that about 70% of benzene emissions
      to air in the UK come from petrol vehicles. A number of studies, including the
      Avon Longitudinal Study of Pregnancy and Childhood in the UK, have found that
      benzene concentrations in homes with attached or integral garages tend to be
      higher than in those without such garages. The present paper reviews these
      studies and reports a detailed investigation of five homes with either an
      attached or an integral garage. Indoor and outdoor locations were monitored using
      diffusive sampling to determine the average benzene concentration over
      approximately 28 days each month for 18 consecutive months (June 1998-November
      1999). For one of these homes, ten years of data had shown the indoor benzene
      concentration to be consistently higher than outdoors. Personal exposure
      monitoring of one adult in this home showed that the benzene concentration in the
      main bedroom was a better predictor of personal exposure than the concentration
      outdoors. In the homes where a car was regularly parked in the garage, 18-month
      average benzene concentrations of up to 101.3 micrograms m-3 were measured in the
      garage, which is more than six times the ambient air quality standard for benzene
      (16.25 micrograms m-3 running annual average). Mean benzene values in all cars
      and most of the garages studied exceeded the benzene standard. Mean benzene
      concentrations in the room above the garage ranged from 3.7 micrograms m-3 in one
      home, where the car was rarely parked in the garage, to 39.9 micrograms m-3 in
      another home where a car with high benzene emissions was parked in the garage for
      six of the 18 months monitored. The mean benzene concentration in the room above
      the garage in this latter home was nearly 2.5 times the ambient air standard. The
      study demonstrates that there is a potential for people to have a higher exposure
      to benzene as a result of living in a home with an attached or integral garage.
      An understanding of routes of personal exposure is important to develop effective
      policies to reduce risks to health.

PMID- 11329697
TI  - Pattern of hand injuries in children and adolescents in a teaching hospital in
      Abha, Saudi Arabia.
AB  - Over a seven-year period, 136 children and adolescents with hand injuries were
      prospectively studied at the Accident and Emergency Department of Asir Central
      Hospital, Abha, Kingdom of Saudi Arabia, to determine the pattern of hand injury.
      The male:female ratio was 1.7:1.0, both left and right hands were relatively
      equally injured. The age group ranged from two months to 16 years (average 5.3
      years). The finger most commonly injured was the middle finger (24.6%) followed
      by the index finger (18.7%). The most common type of hand injury was crush
      injuries caused by doors at home (52.2%), heavy objects (6.6%) and injuries
      caused by grinding machines (6.6%). Since youngsters are often unaware of the
      dangers in their environment it is necessary to redesign the doors of our homes
      with safety devices to prevent injuries. Application of hydraulic automatic door
      closures is a simple but useful way of ensuring smooth and safe closing of doors
      in homes.

PMID- 11329698
TI  - A rapid appraisal method for reviewing the effectiveness of workplace smoking
      policies in large and medium sized organisations.
AB  - Workplace smoking policies have been developed in response to growing scientific
      evidence about the harmful effects of environmental tobacco smoke (ETS),
      increasing opposition from non-smokers, concern over escalating costs of health
      damage and productivity losses, and the emergence of relevant laws and codes of
      good practice. Much has been written on the development and implementation of
      workplace smoking policies, but little about their evaluation. This paper
      describes a rapid appraisal method for the evaluation of workplace smoking
      policies. The four-stage process involves rapid, focused consultation with policy
      makers in the workplace, appropriate risk assessment, rapid consultation with
      those affected by the policy and focused feedback of results for planning and
      ongoing monitoring. In the pilot site the existing health and safety committee
      members were effective informants for the identification of key issues in smoking
      policy. The risk assessment phase was incorporated into the main appraisal which
      involved a canvass of staff and others on ETS issues identified by the
      informants. In the final stage of the process the health and safety committee
      proved to be both responsive to identified need, and proactive in facilitating
      ongoing review of the smoking policy. It therefore proved possible to develop the
      rapid appraisal process for administration in a limited time frame, three months
      for the whole process, with the rapid canvass element being achieved within one
      week.

PMID- 11329699
TI  - Lessons to be learned: a case study approach insulinoma presenting as a change in
      personality.
AB  - A 43-year-old man presented with attacks of altered behaviour over a short period
      of time; they were associated with episodes of hypoglycaemia. The clinical
      suspicion of insulinoma prompted investigations that quickly established serum
      insulin and C-peptide levels to be elevated at the times when blood glucose
      values were low. A physical lesion was found in the head of the pancreas by means
      of computerised tomography and endo-duodenal ultrasound scan; an octreotide scan
      was negative. The patient underwent laparotomy and enucleation of a benign
      tumour, measuring 2.6 cm in diameter, lying within the head of the pancreas;
      histological examination confirmed it to be an insulinoma. Postoperatively, the
      patient's personality gradually became more normal and his fasting blood glucose
      concentrations returned to within normal limits. The diagnosis and management of
      insulinoma are discussed in the context of this clinical case; there is also
      reference to the protean clinical manifestations that may occur in this condition
      and its differential diagnosis.

PMID- 11329700
TI  - Botanical perspectives on health peppermint: more than just an after-dinner mint.
AB  - Throughout history different species of mint have been used across the globe for
      their varying properties, both medicinal and culinary. Today, the commercial
      sales of mints are expanding each year--and at the end of a large meal after
      dinner mints are frequently served. But why do we take them? Peppermint (Mentha
      piperita) is usually taken after a meal for its ability to reduce indigestion and
      colonic spasms by reducing the gastrocolic reflex. It is a naturally occurring
      hybrid cross between water mint (M. aquatica) and spearmint (M. spicata) and is
      best known for its role as a popular flavouring agent. Less well recognised is
      peppermint's potential role in the management of numerous other medical
      conditions including certain procedures, e.g. colonoscopy. With the growing
      popularity of herbal remedies, among both the public and medical practitioners,
      it would seem that now is an opportune time to consider further what peppermint
      has to offer the world of medicine.

PMID- 11329701
TI  - Living conditions and health promotion strategies.
AB  - The paper assesses the empirical evidence concerning the interface between living
      conditions and health status provided by a number of case studies of urban
      regeneration in London, and Brighton and Hove. These studies were carried out in
      the theoretical framework provided by the Cost-effectiveness in Housing
      Investment programme that has been seeking since 1993 to identify and measure
      additional 'exported' costs to services such as health, education and policing
      which derive from poor living conditions. A chronological study of the 'health
      gain' associated with the Central Stepney Single Regeneration Budget improvement
      to two run-down estates indicates that a seven-fold health improvement in the
      rate of 'illness days' experienced has taken place over a four-year period (1996
      2000). This 7:1 differential was identical to that found in the synoptic
      comparison of illness days, and some health and policing costs, between the
      Stepney area and an area of improved housing in Paddington carried out in 1996.
      The paper presents an exploratory attempt to list and categorise in various ways
      the exported costs associated with poor living conditions and offers some
      preliminary assessment of their measurability. Finally, a number of health
      promoting strategies that should be borne in mind when carrying out urban renewal
      programmes are discussed. It is argued that the provision of satisfactory housing
      is a necessary, but not sufficient, condition to promote good health. Attention
      must also be paid to community development, especially of 'organic' activities,
      the quality of services especially in relation to benefits, access to healthy
      food, crime reduction and, critically, the promotion of jobs and the reduction of
      poverty.

PMID- 11329702
TI  - Sorption of lipophilic organic compounds to wood and implications for their
      environmental fate.
AB  - The sorption from water to wood (KWood) of 10 organic chemicals (log KOW, 1.48
      6.20) was experimentally determined for oak (Quercus robur) and basket willow
      (Salix viminalis). Linear regression yielded log KWood = -0.27 (+/- 0.25) + 0.632
      (+/- 0.063) log KOW for oak (r = 0.90, n = 27) and log KWood = -0.28 (+/- 0.40) +
      0.668 (+/- 0.103) log KOW for willow (r = 0.79, n = 27). According to an
      equilibrium-partitioning model, wood should be an important storage compartment
      for lipophilic environmental chemicals, but this is contrary to analytical
      results. Diffusive uptake from air into wood was estimated to be a relevant
      transport process only for chemicals with a high KAW. Uptake of chemicals from
      soil via xylem into stem was simulated with a dynamic one-compartment model. This
      pathway seems to be important for chemicals with low and intermediate
      lipophilicity. In large trees, the chemicals are retained for a long time. If
      metabolism inside the stem occurs, wood can serve as a "safe sink" for
      environmental chemicals. This might be of use in phytoremediation.

PMID- 11329703
TI  - Using fluffy layer material to study the fate of particle-bound organic
      pollutants in the southern Baltic Sea.
AB  - This paper examines the utility of fluffy layer material for studying and
      monitoring the environmental levels, transport, and fate of particle-bound
      contaminants in coastal ecosystems. Fluffy layer material is the very young and
      mobile layer of particulate matter that accumulates on the sediment surface under
      quiescent conditions. We used this material to study the behavior of polycyclic
      aromatic hydrocarbons (PAHs) that are discharged by the Oder River into the
      Baltic Sea. With the fluffy layer material, it was possible to (i) do fingerprint
      analysis to trace the sources of PAHs in the river discharge, (ii) follow the
      modification of the PAHs from the mouth of the river to the depositional basin
      and identify the responsible processes, (iii) monitor the seasonal variation in
      the PAH input, (iv) study the influence of a major flood event on the PAH loading
      to the coastal ecosystem, and (v) conduct a PAH mass balance to estimate the
      contribution of the Oder River source to PAH accumulation in the depositional
      basin. The fluffy layer material integrated the particle-bound contaminant signal
      over a period ranging from several days to several months, depending on the
      sampling location. As such, fluffy layer material is a valuable addition to the
      matrixes commonly used for studying particle-associated chemicals: SPM and
      sediment, which reflect time scales of hours and years, respectively.

PMID- 11329704
TI  - The effects of altitude on heavy-duty diesel truck on-road emissions.
AB  - On-road measurements of carbon monoxide, hydrocarbons, and nitric oxide from 5772
      heavy-duty diesel trucks at five locations in the United States and Europe show
      slightly increasing emissions with increasing altitude. The result for nitric
      oxide showed a statistically significant increase of 4.1 +/- 1 gNO/kg of fuel
      consumed/km increase in altitude. The increases for CO and HC were also
      statistically significant.

PMID- 11329705
TI  - 129I from the nuclear reprocessing facilities traced in precipitation and runoff
      in northern Europe.
AB  - A huge amount of radioactive 129I has been released into the environment from the
      nuclear energy industry, atomic weapon tests, and nuclear accidents. In this
      study, we present weekly and seasonal data on 129I measured in precipitation and
      runoff of northern Europe during 1998 and 1999. The 129I concentration is at
      10(8)-10(9) atoms/L in precipitation and (2-5) x 10(8) atoms/L in runoff water,
      and it is 3-4 orders of magnitude higher than in the prenuclear era. Snow shows
      lower 129I concentration than rain, and there is apparently a positive
      correlation between surface air temperature and 129I. Precipitation chemistry,
      expressed as the content of Cl, SO4, and NO3 and atmospheric ozone, exhibits weak
      negative correlation with 129I values. Our 129I data on precipitation suggest
      significant influence of the northern European atmosphere by the discharges from
      the nuclear reprocessing facilities at Sellafield and La Hague.

PMID- 11329706
TI  - An atmospheric-pressure plasma process for C2F6 removal.
AB  - Perfluorocompounds (PFCs) are widely used in the semiconductor industry for
      plasma etching and chemical vapor deposition (CVD). They are relatively inert
      gases that intensely absorb infrared radiation and, therefore, aggravate the
      greenhouse effect. A bench-scale experimental system was designed and constructed
      to evaluate the effectiveness of C2F6 conversion by using dielectric barrier
      discharges (DBD) with atmospheric-pressure plasma processing. Experimental
      results indicated that the removal efficiency of C2F6 increased with applications
      of higher voltage and frequency. Combined plasma catalysis (CPC) is an innovative
      way for abatement of PFCs, and experimental results revealed that combining
      plasma generation with catalysts could effectively enhance C2F6 removal
      efficiency achieved with DBD. The major products of C2F6 with DBD processing
      include CO2, COF2, and CO, when O2 was included in the discharge process.
      Experimental results indicated that as high as 94.5% of C2F6 were removed via CPC
      at applied voltage of 15 kV, frequency of 240 Hz in the gas stream of
      N2:Ar:O2:C2F6 = 50:40:10:0.03.

PMID- 11329707
TI  - Accumulation of perfluorooctane sulfonate in marine mammals.
AB  - Perfluorooctane sulfonate (PFOS) is a perfluorinated molecule that has recently
      been identified in the sera of nonindustrially exposed humans. In this study, 247
      tissue samples from 15 species of marine mammals collected from Florida,
      California, and Alaskan coastal waters; and northern Baltic Sea; the Arctic
      (Spitsbergen); and Sable Island in Canada were analyzed for PFOS. PFOS was
      detected in liver and blood of marine mammals from most locations including those
      from Arctic waters. The greatest concentrations of PFOS found in liver and blood
      were 1520 ng/g wet wt in a bottlenose dolphin from Sarasota Bay, FL, and 475
      ng/mL in a ringed seal from the northern Baltic Sea (Bothnian Sea), respectively.
      No age-dependent increase in PFOS concentrations in marine mammals was observed
      in the samples analyzed. The occurrence of PFOS in marine mammals from the Arctic
      waters suggests widespread global distribution of PFOS including remote
      locations.

PMID- 11329708
TI  - CoIIIEDTA- reduction by Desulfovibrio vulgaris and propagation of reactions
      involving dissolved sulfide and polysulfides.
AB  - The migration of 60Co, dominantly via transport of Co-EDTA complexes, into
      surface water and groundwater is a recognized concern at many nuclear production
      and storage sites. Reduction of CoIIIEDTA- to CoIIEDTA2- should decrease the
      mobility of 60Co in natural environments by stimulating ligand displacement with
      Fe(III) or Al(III) or by precipitation of CoSx in sulfidic environments. In this
      study, we examine direct (enzymatic) and indirect (metabolite) reduction
      processes of CoIIIEDTA- by the sulfate-reducing bacterium Desulfovibrio vulgaris.
      D. vulgaris reduces CoIIIEDTA- to CoIIEDTA2-, but growth using it as a terminal
      electron acceptor was not demonstrated. Rather than acting as a competing
      electron acceptor and limiting cobalt reduction, introducing sulfate with D.
      vulgaris enhances the reduction of CoIIIEDTA- as a result of sulfide production.
      Sulfide reduces CoIIIEDTA- in a pathway involving polysulfide formation and leads
      to a CoS precipitate. Thus, both direct and indirect (i.e., through the
      production of sulfide) microbial reduction pathways of CoIIIEDTA- may help to
      retard its migration within soils and waters.

PMID- 11329709
TI  - Understanding enantioselective processes: a laboratory rat model for alpha
      hexachlorocyclohexane accumulation.
AB  - Since cyclodextrin gas chromatography columns became popular for chiral
      separations, many researchers have noticed high enantiomeric ratios [ER: (+)
      enantiomer/(-)-enantiomer] for alpha-HCH in the brains of wildlife. This
      investigation used the laboratory rat as a model for these phenomena. Rats were
      either pretreated with phenobarbital (PB) or left untreated and then dosed with
      alpha-HCH. Animals were sacrificed after 1 or 24 h. The ER averaged 0.95 +/- 0.01
      in blood, 1.29 +/- 0.02 in fat, and 0.77 +/- 0.004 in liver. ERs in brain ranged
      from 2.8 +/- 0.5 to 13.5 +/- 0.4. Both the tissue concentration distribution and
      the ERs agree well with those previously reported in wildlife. To determine
      whether high brain ERs were due to enantioselective metabolism or transport
      through the blood-brain barrier, alpha-HCH exposed brain and liver tissue slices
      were compared. Concentrations in the brain slices did not decrease with PB
      pretreatment but did decrease in the liver slices. Enantiomeric ratios in the
      brain slices averaged 1.11 +/- 0.02 and were 0.76 +/- 0.03 in liver slices for
      the PB pretreated rats. These data indicate that the enantioselective metabolism
      of alpha-HCH by the brain is not the mechanism responsible for high ERs in this
      tissue.

PMID- 11329710
TI  - Biofiltration of residual fertilizer nitrate and atrazine by Rhizobium meliloti
      in saturated and unsaturated sterile soil columns.
AB  - This study was undertaken to investigate whether microbial bioaugmentation of
      subsurface soil with subsurface irrigation could be used as a
      biofiltration/biocontrol technology for agricultural pollutants. Nine Plexiglas
      columns, 458 mm long x 139 mm in diameter, were packed with a sterilized sandy
      loam soil. Subsurface irrigation, through a controlled water table management
      system, was used to deliver bacteria, Rhizobium meliloti A-025, to the soil and
      to maintain aerobic (unsaturated) or anaerobic (saturated) conditions in the
      columns. Nitrate and atrazine, a fertilizer and a corn herbicide, were applied to
      the soil surface, and leaching was affected by simulated rainfall events. The
      soil and drainage waters were analyzed for nitrate and atrazine residues after
      each rainfall simulation throughout the experimental period during which the soil
      was kept saturated for a total of 80 days and unsaturated for a total of 70 days.
      The monitoring of transport and survival of the implanted bacterial strain (A
      025) showed that subsurface irrigation was successful in introducing and
      transporting the bacteria throughout the soil columns. During the saturated
      period, significantly more (95% probability) nitrate-N leached into the drainage
      waters from the control columns than from the bioaugmented columns; the increase
      being 450% or more for the abiotic control columns. The amount of atrazine that
      leached into the drainage waters during the unsaturated period was also
      significantly more from control columns as opposed to bioaugmented columns, with
      the increase being 262%.

PMID- 11329711
TI  - De novo synthesis of polychlorinated dibenzo-p-dioxins and dibenzofurans on fly
      ash from a sintering process.
AB  - Fly ash, collected in the electrostatic precipitator of a sinter plant in
      Belgium, has been examined and characterized in terms of its behavior with
      respect to thermal polychlorodibenzo-p-dioxins (PCDD) and polychlorodibenzofurans
      (PCDF) formation. Thermal experiments of the fly ash were conducted in a flow of
      air. The temperature was varied from 250 to 450 degrees C, and the reaction time
      varied from 30 min to 6 h. For comparison, the oxidative degradation of carbon in
      the fly ash was studied by differential scanning calorimetry (DSC) in the
      temperature range from 50 to 500 degrees C. Besides the known maximum of
      formation of PCDD/Fs around 325 degrees C generally found on experiments with
      incinerator fly ash, a second maximum of formation around 400 degrees C is
      observed on the sinter fly ash used in this study. DSC measurements on the fly
      ash show that the oxidative degradation of carbon appears at these two different
      temperatures confirming that the de novo synthesis on this kind of fly ash take
      place at two different optimum temperatures. About the reaction time, already
      after 30 min, an important quantity of PCDD/Fs is formed; the fast increase in
      PCDD/Fs amount is followed by a slower formation rate between 2 and 4 h. At
      longer reaction time, the formation slows down, and decomposition reactions
      become important. Analysis of homologue distribution indicates that the profile
      of PCDD/Fs is independent of the reaction time but that an increase of the
      temperature leads to a rise of lower chlorinated species. In all experiments,
      PCDF are formed preferentially (total PCDF/PCDD ratios larger than 5). The
      PCDF/PCDD ratio is clearly independent of the reaction time. Concerning the
      temperature, the apparently better stability of PCDF at high temperature
      (PCDF/PCDD ratio higher at high temperature) results in the fact of different
      PCDF/PCDD ratios for the different family and modifications of homologue
      distribution with the temperature. The isomer distribution shows little reaction
      time or temperature dependency, which is an argument in favor of a thermodynamic
      control of the isomer distribution during de novo formation of PCDD/Fs.
      Differences within the isomer distribution patterns of PCDD/Fs obtained from the
      laboratory de novo synthesis experiments and the original fly ash, reflecting the
      formation under the industrial process, suggest a different mechanism of
      formation in the sinter plant for the PCDD and PCDF. The de novo synthesis is
      sufficient to explain the PCDF formation in the real process, but synthesis from
      precursors must play a role for the PCDD formation.

PMID- 11329712
TI  - Structure-activity relationships of mineral dusts as heterogeneous nuclei for
      ammonium sulfate crystallization from supersaturated aqueous solutions.
AB  - Mineral inclusions, present in aqueous atmospheric salt droplets, regulate
      crystallization when relative humidity decreases by providing a surface for
      heterogeneous nucleation and thus reducing the critical supersaturation. Although
      laboratory studies have quantified these processes to some extent, the diverse
      atmospheric mineralogy presents more chemical systems than practically feasible
      for direct study. Structure--activity relationships are necessary. To that end,
      in the present work the interactions of ammonium sulfate with corundum, hematite,
      mullite, rutile, anatase, and baddeleyite were studied by diffuse reflectance
      fourier transform infrared spectroscopy (DRIFTS) and by epitaxial modeling. The
      spectroscopic results show that shifts in sulfate peak positions due to
      chemisorption are not a correlative indicator of the efficacy of heterogeneous
      nucleation. In contrast, epitaxial modeling results of unreconstructed surfaces
      explain the sequence of critical supersaturations for constant particle size. If
      validated by further work, this computer modeling method would provide an
      important structure--activity tool for the estimation of heterogeneous nucleation
      properties of the atmospheric mineralogy.

PMID- 11329713
TI  - Evaluation of methods for predicting the toxicity of polycyclic aromatic
      hydrocarbon mixtures.
AB  - Risk assessments of polycyclic aromatic hydrocarbon mixtures are hindered by a
      lack of reliable information on the potency of both mixtures and their individual
      components. This paper examines methods for approximating the toxicity of
      polycyclic aromatic hydrocarbon (PAH) mixtures. PAHs were isolated from a coal
      tar and then separated by ring number using HPLC. Five fractions (A-E) were
      generated, each possessing a unique composition and expected potency. The
      toxicity of each fraction was measured in the Salmonella/mutagenicity assay and
      the Chick Embryo Screening Test (CHEST). Their abilities to induce
      ethoxyresorufin-O-deethylase and to inhibit gap junction intercellular
      communication in rat liver Clone 9 cells were also measured. In the
      Salmonella/mutagenicity assay, fractions were predicted to have potencies in the
      order C > D > E > B > A. Toxic equivalency factors (TEFs) for fractions A-E were
      in the order E > or = D > C > B > A. TEF values were 20,652, 20,929, 441, 306,
      and 74.1 micrograms of BaP equiv/g, respectively. A lack of agreement between
      assay-predicted potencies and chemical analysis-predicted potencies was observed
      with other assays and other methods of calculation. The results demonstrate the
      limitations of using a single method to predict the toxicity of a complex PAH
      mixture.

PMID- 11329714
TI  - Impacts of aging on in vivo and in vitro measurements of soil-bound polycyclic
      aromatic hydrocarbon availability.
AB  - Ingestion of contaminated soil is an exposure pathway at approximately one-half
      of the Superfund sites in the United States. This study was designed to evaluate
      the impacts of aging in soil on the availability of polycyclic aromatic
      hydrocarbons (PAHs). Two coal tar (CT)-amended soils were prepared. One was aged
      for 270 days and the other was not aged. Both of these treatments were
      incorporated into pellets and fed to male Fischer 344 rats. Excretion of 1
      hydroxypyrene (1-OHP) in urine and PAH concentrations in the liver were monitored
      as end points. Additionally, soil:water partitioning and desorption were measured
      as comparisons to the in vivo results. After 5 days of ingesting their respective
      treatments, rats in the aged soil group excreted 4.41 +/- 1.67 ppm 1-OHP/mg of
      pyrene ingested while rats in the unaged soil group excreted 5.27 +/- 1.37 ppm/mg
      of pyrene ingested. Animals fed aged CT soil had 0.051 +/- 0.011 ppm carcinogenic
      PAHs in livers/mg ingested while rats fed unaged CT soil had 0.063 +/- 0.037 ppm
      carcinogenic PAHs in livers/mg ingested. Partitioning and desorption results
      revealed a similar results. These results indicate that, at high application
      rates, soil contact time may not play as significant a role in determining
      availability as simple dispersion and sorption on soil.

PMID- 11329715
TI  - Microbially catalyzed nitrate-dependent oxidation of biogenic solid-phase Fe(II)
      compounds.
AB  - The potential for microbially catalyzed NO3(-)-dependent oxidation of solid-phase
      Fe(II) compounds was examined using a previously described autotrophic,
      denitrifying, Fe(II)-oxidizing enrichment culture. The following solid-phase
      Fe(II)-bearing minerals were considered: microbially reduced synthetic goethite,
      two different end products of microbially hydrous ferric oxide (HFO) reduction
      (biogenic Fe3O4 and biogenic FeCO3), chemically precipitated FeCO3, and two
      microbially reduced iron(III) oxide-rich subsoils. The microbially reduced
      goethite, subsoils, and chemically precipitated FeCO3 were subject to rapid NO3(
      )-dependent Fe(II) oxidation. Significant oxidation of biogenic Fe3O4 was
      observed. Very little biogenic FeCO3 was oxidized. No reduction of NO3- or
      oxidation of Fe(II) occurred in pasteurized cultures. The molar ratio of NO3-
      reduced to Fe(II) oxidized in cultures containing chemically precipitated FeCO3,
      and one of the microbially reduced subsoils approximated the theoretical
      stoichiometry of 0.2:1. However, molar ratios obtained for oxidation of
      microbially reduced goethite, the other subsoil, and the HFO reduction end
      products did not agree with this theoretical value. These discrepancies may be
      related to heterotrophic NO3- reduction coupled to oxidation of dead Fe(III)
      reducing bacterial biomass. Our findings demonstrate that microbally catalyzed
      NO3(-)-dependent Fe(II) oxidation has the potential to significantly accelerate
      the oxidation of solid-phase Fe(II) compounds by oxidized N species. This process
      could have an important influence on the migration of contaminant metals and
      radionuclides in subsurface environments.

PMID- 11329717
TI  - Prediction of principal metal-binding solid phases in estuarine sediments from
      color image analysis.
AB  - A novel application of image analysis technology to the semiquantitative
      determination of the strong metal-binding phases of hydrous ferric oxides and
      acid-volatile sulfides in muddy estuarine sediments is presented. Sediment cores
      were split in the laboratory, photographed in cross-section, and subsampled for
      solid-phase analyses. The images were processed using commercially available
      software packages. Concentrations of FeOOH and AVS were found to be linearly
      related to elementary color parameters (saturation and intensity, respectively)
      at corresponding points on the images. Spatially resolved information on metal
      binding capacity can thereby be estimated from such images; selected depth
      profiles are generated as examples.

PMID- 11329716
TI  - Reaction-based model describing competitive sorption and transport of Cd, Zn, and
      Ni in an acidic soil.
AB  - Predicting the mobility of heavy metals in soils requires models that accurately
      describe metal adsorption in the presence of competing cations. They should also
      be easily adjustable to specific soil materials and applicable in reactive
      transport codes. In this study, Cd adsorption to an acidic soil material was
      investigated over a wide concentration range (10(-8) to 10(-2) M CdCl2) in the
      presence of different background electrolytes (10(-4) to 10(-2) M CaCl2 or MgCl2
      or 0.05 to 0.5 M NaCl). The adsorption experiments were conducted at pH values
      between 4.6 and 6.5 A reaction-based sorption model was developed using a
      combination of nonspecific cation exchange reactions and competitive sorption
      reactions to sites with high affinity for heavy metals. This combined cation
      exchange/specific sorption (CESS) model accurately described the entire Cd
      sorption data set. Coupled to a solute transport code, the model accurately
      predicted Cd breakthrough curves obtained in column transport experiments. The
      model was further extended to describe competitive sorption and transport of Cd,
      Zn, and Ni. At pH 4.6, both Zn and Ni exhibited similar sorption and transport
      behavior as observed for Cd. In all transport experiments conducted under acidic
      conditions, heavy metal adsorption was shown to be reversible and kinetic effects
      were negligible within time periods ranging from hours up to four weeks.

PMID- 11329718
TI  - Enhanced in situ bioremediation of BTEX-contaminated groundwater by combined
      injection of nitrate and sulfate.
AB  - Enhancement of in situ anaerobic biodegradation of BTEX compounds was
      demonstrated at a petroleum-contaminated aquifer in Seal Beach, CA. Specifically,
      combined injection of nitrate and sulfate into the contaminated aquifer was used
      to accelerate BTEX removal as compared to remediation by natural attenuation. An
      array of multi-level sampling wells was used to monitor the evolution of the in
      situ spatial distributions of the electron acceptors and the BTEX compounds.
      Nitrate was utilized preferentially over sulfate and was completely consumed
      within a horizontal distance of 4-6 m from the injection well; sulfate reduction
      occurred in the region outside the denitrifying zone. By combining injection of
      both nitrate and sulfate, the total electron acceptor capacity was enhanced
      without violating practical considerations that limit the amount of nitrate or
      sulfate that can be added individually. Degradation of total xylene appears
      linked to sulfate utilization, indicating another advantage of combined injection
      versus injection of nitrate alone. Benzene degradation also appears to have been
      stimulated by the nitrate and sulfate injection close to the injection well but
      only toward the end of the 15-month demonstration. The results are consistent
      with the hypothesis that benzene can be biodegraded anaerobically after other
      preferentially degraded hydrocarbons have been removed.

PMID- 11329719
TI  - An investigation of the adsorption of C5-C12 hydrocarbons in the ppmv and ppbv
      ranges on Carbotrap B.
AB  - The effects of concentration and temperature on the breakthrough volumes (Vb) of
      23 volatile organic compounds on Carbotrap B have been determined using the
      frontal chromatography method. From the measured Vb, original isotherms have been
      produced and adsorption parameters based on the Langmuir, Freundlich, and Dubinin
      Polyani adsorption models have been calculated. The calculated adsorption
      parameters describe the behavior of these VOC on Carbotrap B under the
      experimental conditions and are useful data for VOC sampling applications
      including adsorption modeling of pumped and diffusive sampling. Each of the
      adsorption models give similar results and are in good agreement with the
      experimental data in the ppmv concentration range. It will be shown that contrary
      to previous assumptions the Langmuir adsorption parameters obtained at ppmv
      concentrations cannot be used to predict Vb at ppbv concentrations and the
      calculated parameter mmax does not represent the maximum adsorbent capacity. The
      Freundlich and Dubinin-Polyani models are shown to be more successful in
      describing the adsorption behavior of the VOC at ppbv levels where Vb is
      independent of concentration. The isosteric heats of adsorption (-delta Hst) for
      some of the compounds have been determined using the Van't Hoff equation which
      can be used to predict the effect of temperature on Vb.

PMID- 11329720
TI  - A distributed reactivity model for sorption by soils and sediments 13. Simulated
      diagenesis of natural sediment organic matter and its impact on
      sorption/desorption equilibria.
AB  - Subcritical water treatment was used to effect rapid compositional and functional
      changes to peat organic matter that mimic those of the natural diagenesis
      process. Elemental, solid state 13C NMR, FTIR, and calorimetry analyses all
      indicated that the organic matter of the artificially aged peat was chemically
      similar to that of geologically mature coal kerogens. This paper extends the work
      of the previous paper in this series, which investigated the effects of
      subcritical water treatment of humic topsoil on subsequent phenanthrene sorption
      and desorption equilibria. As opposed to the previous study, however, changes in
      sorptive reactivity herein were unequivocally related to changes in organic
      matter rather than other soil constituents, and organic matter functional changes
      due to the simulated diagenesis were more accurately characterized. Phenanthrene
      sorption capacity and isotherm nonlinearity both increased with increasing
      degrees of artificial aging, supporting the viewpoint that hydrophobic organic
      contaminant sorption equilibrium properties can be directly related to the degree
      of diagenesis of geosorbent organic matter. In addition, this work investigated
      effects of subcritical water treatment of a geologically mature, kerogen
      containing shale sample. In contrast to the peat, the functional characteristics
      of the shale were unchanged by this treatment, and subsequent phenanthrene
      sorption equilibria were altered far less.

PMID- 11329721
TI  - A distributed reactivity model for sorption by soils and sediments. 14.
      Characterization and modeling of phenanthrene desorption rates.
AB  - Rates and extents of phenanthrene desorption were studied for more than 250 days
      as functions of sorbent type, initial loading level, and aging. Apparent first
      order desorption rate constants for the slowly desorbing fraction were found to
      (i) range from 0.00086 to 0.148 days-1 for geosorbents that contain geologically
      mature kerogen and less rigid humic-type soil organic matter, respectively, (ii)
      decrease by as much as an order of magnitude with decreasing initial sorbed solid
      phase phenanthrene concentration, (iii) decrease by a factor of 2 with increasing
      aging time for a humic topsoil but remain unaffected by aging time beyond 3
      months for a shale, and (iv) be 1-2 orders of magnitude lower than rate constants
      for the rapidly desorbing phenanthrene fractions for any given contaminated
      sample. Six models were used to fit the desorption rate data. Biphasic diffusion
      and biphasic first-order models with three fitting parameters possess broad
      utility and are potentially useful in a variety of environmental applications.
      Disadvantages of a five-parameter triphasic first-order desorption model, a two
      parameter gamma-function model, and a one- or two-parameter pore diffusion model
      are also discussed.

PMID- 11329722
TI  - Comment on "Life-cycle analysis of alternative automobile fuel/propulsion
      technologies".

PMID- 11329723
TI  - Searching for sexually explicit materials on the Internet: an exploratory study
      of college students' behavior and attitudes.
AB  - The convergence of sexuality messages with a computerized medium (specifically,
      the Internet) represents an unprecedented phenomenon with, as of yet, unknown
      outcomes. Despite the Internet's widespread use, little is known about users'
      behaviors and attitudes when searching for sexually explicit materials online.
      This study examined specific behaviors and outcome expectations and expectancies
      (or attitudes) of a sample of 506 undergraduate students at a public university
      in Texas. Data were collected through a self-administered questionnaire, designed
      and pretested by the authors. Main results revealed that most students in the
      sample were infrequent and relatively new users of the Internet. Forty-three
      percent (43.5%) of students had sometime accessed sexually explicit materials
      through the Internet, but the practice was not very common. Only 2.9% said they
      accessed these materials "frequently." Male students were significantly more
      likely to have accessed the Internet for viewing sexually explicit materials and
      to claim curiosity about sex as their motivation for this behavior. Women were
      significantly more likely to have experienced sexual harassment while online. In
      terms of attitudes, this sample did not appear to value highly or exhibit strong
      beliefs about the potential outcomes associated with accessing the Internet for
      sexually explicit materials. Competing explanations as well as the limitations of
      this study are discussed.

PMID- 11329724
TI  - Extra relationship involvement among women: are they different from men?
AB  - Factors related to three types of Extra Relationship Involvement (ERI) in women
      were explored: emotional ERI, sexual ERI, and a combination of sexual and
      emotional ERIs. A model, based on a decision-making model of male ERI and the
      additional variable of commitment, was evaluated. The research involved two
      studies with female participants (N = 112, N = 44) who had been involved in
      heterosexual relationships of at least 6-month duration. The major finding was
      that women engage in emotional and combined ERIs but rarely enter into solely
      sexual ERIs. It was demonstrated that social norms, planning, relationship
      satisfaction, and commitment were influential in predicting emotional and
      combined ERI intentions. Past ERI behavior was a strong predictor of future
      emotional and combined ERI behavior, but planning also added to the prediction of
      combined ERI behavior. Women who had engaged in emotional ERIs and combined ERIs
      indicated romantic affect as the main reason for their ERI behavior. Overall, it
      was demonstrated that women's intentions to engage in ERI were related to
      cognitive processes and relationship variables, and that ERI behavior, although
      generally habitual, was also predicted by cognitive processes.

PMID- 11329725
TI  - A framework for the formation of gay male identity: processes associated with
      adult attachment style and support from family and friends.
AB  - We propose a novel conceptual framework for the study of gay male identity
      formation in relation to the person's self, family, and social relations. The
      three basic processes of gay male identity are defined--self-definition, self
      acceptance, and disclosure--and theoretically linked to attachment style and
      social support. The results, based on an Israeli sample of gay men (n = 121),
      indicated that self-acceptance and friends' support predict secure attachment in
      close adult relationships, and that self-definition and support from family and
      friends predict disclosure. Supportive family attitudes toward same-sex
      orientation mediated the effect of general family support on disclosure. These
      results suggest that the independent assessment of identity processes provides a
      flexible alternative to stage models' assumption of a single linear developmental
      process, that the formation of gay identity is associated with inner models of
      adult relationships, and that support of family and friends have a different role
      in the coming out process and in the formation of one's adult attachment model.

PMID- 11329726
TI  - Which behaviors constitute "having sex" among university students in the UK?
AB  - The aim of this study was to establish which behaviors were considered to
      constitute sexual relations and to compare a group of undergraduates in the UK
      with a group in the US. An opportunistic sample of 190 female and 124 male UK
      undergraduate university students was surveyed by questionnaire. The main outcome
      measure was percentage of responses to 11 different behaviors believed to
      constitute "having sex." The majority of respondents regarded having sex as
      involving penile-vaginal and penile-anal intercourse. One-third of respondents
      regarded oral-genital contact as having sex, around 17% regarded touching
      genitals, whilst 6% regarded oral or other touching of breasts and nipples as
      constituting having sex. There were significant gender- and age-related
      differences in responses. These findings broadly support the findings of an
      earlier US study. It is clear that British students hold divergent opinions about
      which behaviors do and do not constitute having sex. The age-related trends merit
      further exploration. Any studies of sex-related behaviors need to specify
      precisely which are encompassed by the terms used.

PMID- 11329728
TI  - [Ebola fever: an emerging disease].
AB  - One of the most fatal diseases encountered by mankind so far is Ebola fever.
      Ebola fever is caused by a highly pathogenic virus from the Filoviridae family
      which is found in nature in four different sub-types which differ among others
      also by their pathogenicity for man. The hitherto detected EBO sub-types are
      stable do not change in the course of an epidemic nor in the course of the
      patient's illness, nor during passage of the virus from one subject to another.
      The author presents a historical review of epidemics, nosocomial and laboratory
      infections, spread and epizoonosis caused by the Ebola virus. The author presents
      a detailed clinical picture describing the frequency and evolution of different
      clinical symptoms and signs based on the observation of 103 patients infected
      with the Ebola virus in Kikwit, Zaire (nowadays Democratic Republic of Congo) in
      1995. In the laboratory diagnosis individual tests are mentioned assessing the
      presence of the virus, viral antigens and antibodies, incl. the most recent
      immunohistochemical test. The author mentions the problem of patient care and his
      therapy, incl. available antiviral drugs and passive immunotherapy. He also
      discusses the possibility and probability of spread of the Ebola virus into our
      environment. He mentions principles for transport of subjects with suspected
      disease, demands for their strict isolation and maximum protection of the
      attending staff incl. barrier nursing technique. The author discusses also
      principles of epidemiological work, detection and isolation of sources,
      identification and follow up of contacts and epidemiological supervision of
      affected areas. Past epidemics made it possible to assemble many scientific
      findings and practical experience. These make it possible to cope nowadays with
      any attack of the Ebola virus not only in areas of its epizootic occurrence.

PMID- 11329729
TI  - [Diagnosis of the early phase of larval toxocariasis using IgG avidity].
AB  - The term avidity used to express the strength of the bond between a serum
      specimen and a multivalent antigen. It is known that the avidity increases with
      time after antibody challenge and measurement of the avidity has been used
      diagnostically. Recently an assay measuring the IgG avidity of various virus
      infections and of toxoplasmosis was used to distinguish between acute and chronic
      infection. Our study was focused on the method to distinguish acute and chronic
      Toxocara infection, zoonosis caused by the larvae of dog and cat ascarids
      Toxocara canis and Toxocara cati known all over the world for the possibility of
      provoking the infestation of man, accompanied by visceral or ocular clinical
      manifestations. The infection is generally diagnosed by demonstration of specific
      immunoglobulins to Toxocara excretory-secretory antigens (TES) in sera of
      infected patients. Highly sensitive assays with specific antigens are necessary
      for detection of antibodies. The test that has been proved clinically useful is
      the ELISA reaction with TES antigens. This method detects the antibodies for
      months or even years after infection and this is the reason why the
      discrimination between chronic and recent infection is very difficult. For
      disrupting the hydrogen bond urea has been used. The index of avidity was
      calculated as the ratio of IgG values in sera treated with urea and the value of
      IgG in non-treated sera, multiplied by 100. An index up to 40 is considered as
      low avidity, that means freshly acquired infection (36 to 40 borderline) and more
      than 40 is high avidity. In the group of 1,376 patients only 5.09% low avidities
      were found. It means that predominantly patients in the chronic stage of
      infection attend examination.

PMID- 11329727
TI  - Prevalence of sexual dysfunctions: results from a decade of research.
AB  - Ten years of research that has provided data regarding the prevalence of sexual
      dysfunctions is reviewed. A thorough review of the literature identified 52
      studies published in the 10 years since an earlier review by Spector and Carey
      (Arch. Sex. Behav. 19(4): 389-408, 1990). Community samples indicate a current
      prevalence of 0%-3% for male orgasmic disorder, 0%-5% for erectile disorder, and
      0%-3% for male hypoactive sexual desire disorder. Pooling current and 1-year
      figures provides community prevalence estimates of 7%-10% for female orgasmic
      disorder and 4%-5% for premature ejaculation. Stable community estimates of the
      current prevalence of other sexual dysfunctions remain unavailable. Prevalence
      estimates obtained from primary care and sexuality clinic samples are
      characteristically higher. Although a relatively large number of studies has been
      conducted since the earlier review, the lack of methodological rigor of many
      studies limits the confidence that can be placed in these findings.

PMID- 11329730
TI  - [Detection of Arcanobacterium haemolyticum in primoculture using the reverse CAMP
      test].
AB  - Arcanobacterium haemolyticum was isolated from 8,641 throat swabs in 49 cases
      (0.56%), from patients aged 16 to 24 years only, twice more often from men than
      from women. The isolation was achieved on sheep blood agar supplemented with
      streak with Staphylococcus aureus strain producing beta-lysine. In all cases the
      presence of A. haemolyticum colonies was disclosed by the irregular periphery of
      haemolysis around the staphylococcal streak after the 48-hour incubation. The
      technique described should be used as a standard procedure for examining throat
      swabs.

PMID- 11329731
TI  - [Culture of Borrelia burgdorferi sensu lato from patients in the Czech Republic].
AB  - Spirochete of Borrelia burgdorferi sensu lato were isolated in a modified BSK
      medium from 26 patients of 275 investigated suffering from early and late
      borreliosis. The isolates were specified by phenotype and genotype analysis using
      monoclonal antibodies, by immunochemical methods and by including species
      specific 16S rRNA, OspA and OspC primers and probes in a polymerase chain
      reaction with hybridization. Borrelia afzelii was found in 9 patients, Borrelia
      garinii in 16 and B. burgdorferi sensu stricto in one instance. B. afzelii was
      isolated from 5 biopsies with erythema migrans. 2 with acrodermatitis chronica
      atrophicans and from blood of 2 patients with arthritis. B. garinii cultures were
      prepared from 6 cerebrospinal fluids, 3 blood samples, 1 placenta, 1 liver biopsy
      and 5 skin samples. Unique was B. burgdorferi detected in a bioptic sample of the
      heart muscle which was positive on immunohistochemical examination. Monoclonal
      antibodies against OspA and genotype analysis provided evidence that Borrelia
      garinii isolates from cerebrospinal fluid are close to serotype IV. One CSF
      isolate was resistant to antibiotics; the tropism of B. garinii to nervous tissue
      is contemplated.

PMID- 11329733
TI  - [Free radicals in immunology and infectious diseases].
AB  - Free radicals contribute significantly in modification of immune processes and
      inflammatory reactions. They are produced by activated phagocytes which use them
      for killing microorganisms. Free radicals facilitate production of cytokines,
      which are important as modifiers of inflammatory reactions. Formation of free
      radicals is influenced by antioxidants which can thus modify the intensity of
      inflammatory reaction and immune response. The authors describe in detail the
      contribution of free radicals in etiology and pathogenesis of autoimmune diseases
      including rheumatoid arthritis, multiple sclerosis or amyotrophic lateral
      sclerosis. The role of free radicals and modifying influence of antioxidants in
      viral, bacterial, parasitic and mycotic diseases is described in the second part
      of the review. Finally, influence of free radicals and antioxidants on immunity
      changes in patients with malignant tumours, during aging and physical exercise is
      discussed.

PMID- 11329732
TI  - [DRE-PCR (Double Repetitive Element-Polymerase Chain Reaction)--a new molecular
      epidemiologic method in the detection of tuberculosis].
AB  - In a pilot study Double Repetitive Element-Polymerase Chain Reaction 20 clinical
      isolates of Mycobacterium tuberculosis from Guatemala and 49 strains from Prague
      were typed. This technique is based on direct evidence of repetitive elements
      IS6110 or PGRS and does not require DNA purification, digestion by endonuclease
      nor Southern blot hybridization. Preliminary examination of Guatemalian strains
      revealed a striking identity or similarity of DRE-PCR profiles while the Prague
      strains were characterized by conspicuous polymorphism. The Prague strains were
      examined in a total number of 13 series of electrophoreograms and subsequently
      subjected to automated analysis with GelCompar software. The DRE-PCR method is
      suitable for screening of a major number of clinical isolates of M. tuberculosis
      in laboratories equipped with a minimum of technical facilities for the PCR
      method, furthermore it requires facilities for synthesis of the necessary primers
      and at least basic knowledge of molecular biology.

PMID- 11329734
TI  - [Klebsiella species from the viewpoint of nosocomial infections and virulence
      factors].
AB  - The author reviewed data on Klebsiella species mainly in connection with their
      participation in nosocomial infections, with their antibiotic resistance and
      production of ESBL. Potential virulence factors of Klebsiella are also evaluated.

PMID- 11329735
TI  - Informed consent and randomised controlled trials.
AB  - Truly informed consent is a difficult thing to achieve! Patients are not healthy
      volunteers and their vulnerability challenges their ability to assess the
      risk/benefit of health choices. In this paper we consider some or the issues
      surrounding this important aspect of modern practice, and offer some suggestions
      on how to improve the process, with the goal of increasing participation in
      clinical research, and enhancing patients' confidence in their medical advisors.

PMID- 11329736
TI  - Superficial parotidectomy through retrograde facial nerve dissection.

PMID- 11329737
TI  - Splenogonadal fusion: report of a rare variety.
AB  - We report an unusual case of splenogonal fusion in a 10-year-old boy with an
      undescended left testis. He suffered from congenital limb defects, a known
      association with splenogonadal fusion, and had originally been admitted for
      orchidopexy.

PMID- 11329738
TI  - Emergency laparoscopic orchidectomy for torsion of intra-abdominal testis: a case
      report.
AB  - Torsion of an intraabdominal testis is a rare cause of acute abdominal pain. With
      a history of undescended testis, it is difficult to establish the diagnosis and
      to exclude other emergency abdominal conditions without a laparotomy. The
      following case report illustrates the usefulness of laparoscopy as a diagnostic
      as well as a therapeutic tool in such a condition.

PMID- 11329739
TI  - Penetrating neck trauma: hidden injuries-oesophagospinal traumatic fistula.
AB  - Injuries to the eosophagus are notoriously difficult to diagnose pre-operatively.
      Patients with such injuries usually will not have pre-operative signs and
      symptoms to suggest the presence of this type of injury. These injuries require a
      high index of suspicion, appreciation of the presence of injuries to adjacent
      structures, and an understanding that the clinical and radiological findings may
      evolve over a period of time. We describe a child with a rare presentation of an
      acute traumatic esophageal spinal fistula due to a bullet wound. This complicated
      injury required a variety of diagnostic modalities, including contrast
      radiography, multiple computerised tomography (CT) scans and operative
      assessments to make the definitive diagnosis.

PMID- 11329740
TI  - Diagnosis of a femoral hernia in the elective setting.
AB  - A femoral hernia accounts for approximately 5-10% of all groin hernias in adults.
      Misdiagnosis in children, in whom the condition is rare, has been well recognised
      and documented. The aim of this study was to assess the accuracy of diagnosis in
      an adult population. METHODS: An analysis of 379 patients with a groin hernia,
      presenting electively to a University Department of Surgery and entered into a
      prospective clinical trial. RESULTS: A femoral hernia was confirmed at operation
      in 12 (3%) patients while a further 4 had a preoperative diagnosis of a femoral
      hernia. The correct diagnosis of a femoral hernia was made in only 3 cases by
      general practitioners and in only 6 by surgical staff of all grades. CONCLUSION:
      These data suggest that medical staff of all grades may be poor at diagnosing a
      femoral hernia and a change in the way we are taught to differentiate between
      femoral and inguinal hernia needs to be considered.

PMID- 11329741
TI  - The other brother--a brief account of the life and times of Frederick John Knox
      LRCSEd.
AB  - This article examines the career of Frederick John Knox (1794-1873), who was the
      younger brother and erstwhile assistant of Robert Knox the anatomist. He was
      licensed by the Royal College of Surgeons of Edinburgh in 1831, and in 1840 he
      emigrated with his wife and family to New Zealand, becoming a significant figure
      in the scientific community of the infant settlement of Wellington.

PMID- 11329742
TI  - The management of sigmoid volvulus.

PMID- 11329743
TI  - Facial nerve palsy following intra-oral surgery performed with local anaesthesia.

PMID- 11329744
TI  - Centralisation of oesophageal cancer services: the view from the periphery.

PMID- 11329745
TI  - Sepsis and the systemic inflammatory response syndrome.

PMID- 11329746
TI  - Current status of medicine in the USA: a personal perspective.

PMID- 11329747
TI  - Surgical management of radial head fractures.
AB  - OBJECTIVE: To compare the outcome of various surgical options exercised in the
      management of different types of radial head fractures. METHOD: A retrospective
      study of 29 patients with radial head fractures managed surgically was
      undertaken. Case notes were retrieved, and final assessment was performed through
      a telephone questionnaire. The results were analysed according to the
      classification of Wesley et al (1983), and compared with the patients' own
      rating. RESULTS: The best results were obtained in Mason type II fractures,
      followed by type III and type IV fractures. Comparing different operations, the
      best outcome was observed with screw fixation, followed by excision of the radial
      head, Kirschner wire fixation, partial excision, silastic implant, and plating,
      in that order. CONCLUSION: The less comminuted a radial head fracture is, the
      better the outcome. Screw fixation is to be preferred, if technically possible.
      Our method of outcome assessment closely reflected in patient satisfaction.

PMID- 11329748
TI  - Thyroid auto-antibodies, lymphocytic infiltration and the development of post
      operative hypothyroidism following hemithyroidectomy for non-toxic nodular
      goitre.
AB  - BACKGROUND: Auto-immune thyroiditis, associated with detectable thyroid auto
      antibodies (TAAs) and lymphocytic infiltration into the gland, is known to be
      associated with progressive development of hypothyroidism. This study examines
      those patients who required surgical treatment of non-toxic nodular goitre by
      hemithyroidectomy to determine whether the presence of TAAs in the circulation
      and/or lymphocytic infiltration of the gland resulted in a significant degree of
      post-operative hypothyroidism. METHOD: This was a prospective study, with data
      collected retrospectively. All patients operated on for thyroid disease in the
      unit over a 5-year period were documented, and those patients treated by
      hemithyroidectomy for non-toxic nodular goitre formed the study group. TAAs were
      measured, histology re-examined and patients followed up for at least 2 years to
      detect clinical or sub-clinical hypothyroidism. RESULTS: Of the 158 patients who
      comprised the study group, 38 (24.1%) developed hypothyroidism. Forty-one (25.9%)
      had circulating levels of TAAs, 31 of these (75.6%) having high levels. Of these
      41 patients, 22 (53.7%) became hypothyroid. Twenty (64.5%) of the 31 patients
      with high levels of TAAs required post-operative thyroxine. Of the remaining 117
      patients with no detectable TAAs, only 16 (13.7%) became hypothyroid. CONCLUSION:
      All patients requiring treatment by hemithyroidectomy should have circulating TAA
      measurements carried out pre-operatively. If positive, they should be followed up
      indefinitely because of the strong possibility (P < 0.001) of the development of
      hypothyroidism.

PMID- 11329749
TI  - Signs and symptoms of malignant parotid tumours: an objective assessment.
AB  - BACKGROUND: The clinical features that may be associated with malignancy in
      parotid tumours are well known. Classical teaching dictates caution in their
      presence but this raises a false alarm in many cases. Formal studies looking at
      these features are few. The aim of this article was to study quantitatively those
      features that provide a better prediction of malignancy. METHODS: Clinical
      records of 186 consecutive patients treated for parotid tumours over a 12-year
      period were reviewed. Presence of suspicious clinical features and the final
      histology in each patient were noted. RESULTS: The overall pick-up rate for
      malignancy, based on clinical features alone, was around 30%. Palpable cervical
      lymph nodes, facial nerve palsy, deep fixation and rapid enlargement of the
      tumour were significant parameters indicative of malignancy (p = 0.000 for all 4
      parameters, chi-squared test). The risk of malignancy increased when multiple
      parameters were present together at the same time. CONCLUSION: Clinical features
      remained the most important single modality identifying malignancy in patients
      with parotid tumours. The logistic regression model allowed for simple clinical
      prediction of malignancy with improved sensitivity and much better specificity.

PMID- 11329750
TI  - Experience with a one-stop colorectal clinic.
AB  - BACKGROUND AND OBJECTIVE: Colorectal services have traditionally been arranged
      for the convenience of hospitals rather than patients. This model is not ideal,
      particularly for minor interventions and diagnostic procedures. In order to
      address this a one-stop colorectal clinic was set up. PATIENTS AND METHODS:
      Weekly clinics ran from 6.00 to 9.30 p.m. on Wednesdays for a period of 6 months.
      Patients with rectal bleeding, altered bowel habit, anorectal symptoms and those
      requesting screening advice were seen by a consultant or specialist registrar.
      Patients were asked to fill in a questionnaire at the end of their clinic
      attendance. RESULTS: 197 patients were seen in 17 clinics; 134 underwent
      proctoscopy, 72 had a rigid sigmoidoscopy and 85 had a flexible sigmoidoscopy
      carried out. Twenty-four patients subsequently had a barium enema and 3 were
      listed for colonoscopy. The main diagnosis was haemorrhoids (n = 104); 14
      colorectal neoplasms were discovered (5 cancers and 9 polyps). During the study
      period the number of patients waiting for lower gastrointestinal endoscopy fell
      from 119 to 63; 2 months after ending the pilot scheme, the number had risen to
      108. CONCLUSION: The clinic was found to have significantly improved patient
      care. The majority of patients were satisfied with an evening clinic. Flexible
      sigmoidoscopy without sedation was well tolerated and the ability to perform this
      at initial assessment had a marked effect on the number of patients awaiting
      lower gastrointestinal endoscopy.

PMID- 11329751
TI  - An audit of the management of the acute scrotum in children with Henoch-Schonlein
      Purpura.
AB  - Many children with Henoch-Schonlein anaphylactoid purpura syndrome (HSAPS) who
      develop an acute scrotum have scrotal explorations to exclude torsion of the
      spermatic cord. However, the cause of the acute scrotum in the context of HSAPS
      is known to be vasculitis and not torsion. The aim of this study, therefore, was
      to identify factors that underlie this practice. In a 10-year retrospective study
      of male patients admitted to a Children's Hospital with a diagnosis of HSAPS, 22
      out of the 93 children identified (22/93 = 24%) had scrotal involvement. Three
      children (3/22 = 14%) were investigated radiologically, eight children (8/22 =
      36%) had surgical exploration and none had testicular torsion. We believe that
      greater awareness of the syndrome and its clinical presentation amongst
      paediatric surgical staff could allow the adoption of a conservative approach in
      children with an unequivocal diagnosis of HSAPS provided such an approach is
      supported by high resolution colour Doppler sonography and a fully informed
      parental consent. Surgical exploration is indicated if the diagnosis of the
      syndrome is not beyond doubt and torsion cannot be excluded on clinical grounds.

PMID- 11329752
TI  - Federal court strikes down compounding regulations.

PMID- 11329753
TI  - Knowing patient's allergies, pharmacist had duty to warn, says Illinois court.

PMID- 11329754
TI  - Omeprazole isomer approved by FDA.

PMID- 11329755
TI  - FDA approves galantamine for Alzheimer's disease.

PMID- 11329756
TI  - Pharmacy services in community and migrant health centers studied.

PMID- 11329757
TI  - Direct feedback program gets to heart of improved order writing.

PMID- 11329758
TI  - Soy for cardiovascular indications.

PMID- 11329759
TI  - Angiotensin II-receptor blockers: clinical relevance and therapeutic role.
AB  - The limitations of angiotensin-converting-enzyme (ACE) inhibitors and the role of
      angiotensin II-receptor blockers (ARBs) in the treatment of hypertension, heart
      failure, and diabetic nephropathy are discussed. Although ACE inhibitors are
      generally well tolerated, two important class-related adverse effects are cough,
      which is common, and angioedema, which is rare but serious. Cough and angioedema
      appear to be less frequent with ARBs than with ACE inhibitors. ARBs seem to be as
      capable as ACE inhibitors of producing renal dysfunction. ARBs may offer more
      complete inhibition of angiotensin II than ACE inhibitors. The mechanism of
      action is based on selective binding to angiotensin type 1 receptors. Many
      clinical studies have shown that ARBs lower blood pressure as effectively as
      other antihypertensive agents, including ACE inhibitors. ARBs do not appear to
      have a greater clinical effect than ACE inhibitors in patients with heart
      failure. Some studies of combination ARB and ACE inhibitor therapy for heart
      failure indicate advantages of the combination over therapy with either class.
      ARBs may exert renal protective effects in diabetic nephropathy. ARBs offer an
      alternative to ACE inhibitors in the management of hypertension, especially for
      ACE-inhibitor-intolerant patients. ACE inhibitors remain the drugs of choice for
      patients with heart failure, left ventricular dysfunction after MI, and diabetic
      nephropathy; ARBs offer these patients an alternative when ACE inhibitor therapy
      is not tolerated.

PMID- 11329760
TI  - Clinical impact of interlaboratory variation in international normalized ratio
      determinations.
AB  - Variation among laboratories and point-of-care (POC) devices in International
      Normalized Ratio (INR) determinations for individual patients in the same
      community was studied. For each patient, blood samples obtained from a single
      venipuncture followed by a finger stick were tested at three laboratories and
      with two POC devices. A nonparametric analysis of variance and regression
      analysis were used to compare INRs across sources. The potential clinical impact
      of differences between pairs of INR readings (i.e., whether a difference was
      likely to result in a change in therapy) was evaluated. Complete data were
      obtained and analyzed for 41 patients. Of the five sources of INRs, results from
      two laboratories and one POC device were significantly similar. Results from one
      laboratory and one POC device were significantly different from the other
      results. Variation between INR readings from two different sources might have
      resulted in a change in therapy 10-30% of the time. Variations occurred in INR
      readings among three laboratories and two POC devices and could have led to a
      substantial number of inappropriate changes in therapy.

PMID- 11329762
TI  - Survey of computerized documentation system use in drug information centers.

PMID- 11329761
TI  - Pharmacokinetic comparison of omeprazole capsules and a simplified omeprazole
      suspension.
AB  - The pharmacokinetics of omeprazole delayed-release capsules and a simplified
      omeprazole suspension (SOS) were studied. Seven healthy volunteers randomly
      received either one 20-mg omeprazole delayed-release capsule or SOS (omeprazole
      20 mg in 10 mL) for seven days before being crossed over to the opposite
      treatment for seven more days after a two-week washout period. On days 1 and 7,
      blood samples were drawn at intervals up to 360 minutes after drug
      administration. Plasma omeprazole concentrations were determined by a validated
      high-performance liquid chromatographic method, and pharmacokinetic values were
      determined. Area under the concentration-versus-time curve (AUC) from zero to six
      hours, AUC from time zero to infinity (AUC0-infinity), and maximum plasma
      concentration (Cmax) increased by 102%, 113%, and 85%, respectively, after seven
      days of treatment with the capsule. AUC0-infinity for SOS on day 1 was 58% of
      that for the capsule (p = 0.0141), and on day 7 it was 49% of that for the
      capsule (p = 0.0044). AUC0-infinity for SOS increased by 85% from day 1 to 7, but
      the difference was not significant. Cmax for SOS on day 1 was twice that for the
      capsule (p = 0.0014), but by day 7 the difference between the two formulations
      was negligible. Time to Cmax (tmax) for SOS on days 1 and 7 was shorter than for
      the capsule by 82% (p < 0.0001) and 70% (p < 0.0006), respectively. After one
      week of therapy, omeprazole absorption was faster and tmax was 70% shorter for
      SOS than for the capsule formulation, but AUC0-infinity was 49% lower for SOS.

PMID- 11329763
TI  - Functionalized biopolymers as soluble macromolecular chelating agents.
AB  - Two different conjugates of bovine serum albumin (BSA) with lysine and a
      derivative of imidazole have been synthesized to obtain watersoluble
      macromolecules with binding properties against bivalent transition metal ions.
      Syntheses have been carried out using the 60 aminogroups or the 99 carboxylic
      groups on BSA for the coupling reactions, with such molar ratios able to produce
      highly substituted BSA. The skill of each conjugate to bind metal ions in aqueous
      medium was studied through the use of titration curves with some metal ions,
      characterized by a good affinity for the free ligand. Both the conjugates allow
      us to recover a high number of metal ions per protein molecule, close to the
      number of ligand molecules on the BSA surface in the case of the lysine
      conjugate, whereas in the case of the imidazole conjugate M3L complexes are
      performed.

PMID- 11329764
TI  - Determination of nickel in biological samples spectrophotometrically involving
      complexation reaction with some thiazolylazo compounds.
AB  - Three new heterocyclic azo compounds, 5(2-benzothiazolylazo)2,2 biphenyldiol (I),
      5-(2-benzothiazolylazo)-8-hydroxyquinolene (II) and 4-(2-benzothiazo-lylazo)3
      hydroxy-2-naphthoic acid (III) were synthesized. The formation constant of the
      reagents in 30% (v/v) ethanol and reactions with various metal ions were studied.
      These reagents (I-III) reacts with nickel ion to form (2:1) colored complex with
      an absorption band at 604, 635 and 643 nm. The apparent stability constants and
      the optimum conditions for complete color development were investigated. Beer's
      law is obeyed over the concentration ranges of 0.05-3.50, 0.05-4.00 and 0.05-3.10
      micrograms ml-1. For more accurate analyses, Ringbom optimum concentration ranges
      were found to be 0.20-3.25, 0.20-3.80 and 0.20-2.90 micrograms ml-1 using
      reagents I, II and III, respectively. The apparent molar absorptivity and Sandell
      sensitivity were also calculated. The interference of various foreign ions on the
      determination of nickel was investigated. The proposed method has been
      successfully applied to the determination of nickel substrates in various
      biological samples.

PMID- 11329765
TI  - Thin layer chromatography of toxic metals on mixed bed of titania and silica.

PMID- 11329766
TI  - Bioaccumulation of vanadium in the epiphytic lichen Parmelia caperata from
      Liguria (north-west Italy).
AB  - The concentration of vanadium was measured in 35 samples of the epiphytic lichen
      Parmelia caperata collected along the coast of the Ligurian Sea (Italy), in order
      to detect the possible bioaccumulation of vanadium due to a huge crude oil
      burning occurred in that area in 1991. The cartographic elaboration of data shows
      a pattern of distribution of vanadium concentrations according to different
      degrees of deviation from background condition, showing that 8 years later memory
      of the accident is still detectable in foliose lichen thalli.

PMID- 11329767
TI  - Envirometrics. Part I: Modeling of water salinity and air quality data.
AB  - Envirometrics utilises advanced mathematical, statistical and information tools
      to extract information. Two typical environmental data sets are analysed using
      MVATOB (Multi Variate Analysis TOol Box). The first data set corresponds to the
      variable river salinity. Least median squares (LMS) detected the outliers whereas
      linear least squares (LLS) could not detect and remove the outliers. The second
      data set consists of daily readings of air quality values. Outliers are detected
      by LMS and unbiased regression coefficients are estimated by multi-linear
      regression (MLR). As explanatory variables are not independent, principal
      component regression (PCR) and partial least squares regression (PLSR) are used.
      Both examples demonstrate the superiority of LMS over LLS.

PMID- 11329768
TI  - Conservation studies on ornamental and building stones of north-eastern Sicily.
      Geomineralogical and porosimetric investigations.
AB  - The effectiveness, as preserving agents, of a series of chemical compounds
      (silanes, siloxanes, epoxides, perfluoropolyethers, acrylates, acrylsilicones)
      has been tested on lithic materials mainly used in artistic stoneworks of north
      eastern Sicily. The selection and classification of the stone types, based on
      geomineralogical criteria follows a brief excursus about their use as artistic
      materials. The results of the porosimetric investigations, before and after
      conservation treatments, are reported. In addition, polarizing mineralogical
      microscope photos of the studied lithoid materials are presented.

PMID- 11329769
TI  - Conservation studies on ornamental and building stones of north-eastern Sicily.
      Hydric and colorimetric investigations.
AB  - In this paper we report on the results regarding the hydric properties of lithic
      materials widely used in north-eastern Sicily. We report also on the hydrophobic
      properties of these stones treated with some preserving products (silanes,
      siloxanes, epoxides, perfluoropolyethers, acrylates, acrylsilicones). In
      addition, the quantitative colour readings of the untreated and treated stones
      are presented, together with their chromatic alterations after artificial UV
      weathering. Final considerations on the selection of the best regime treatment
      are also reported.

PMID- 11329770
TI  - Heavy metal determination in aquatic species for food purposes.
AB  - New analytical procedures and sample mineralizations are proposed regarding the
      determination of arsenic, selenium, copper, lead, cadmium, zinc and mercury in
      matrices involved in food chain as mussel, clams and fishes. As regard As, Se,
      Cu, Pb, Cd and Zn determinations, H2SO4-HNO3 acidic mixture is used for the
      digestion of each matrix. In the case of Hg the sample digestion is performed
      using a concentrated suprapure H2SO4-K2Cr2O7 mixture and the results are compared
      with those from other conventional methods. Differential pulse cathodic (DPCSV)
      and anodic stripping voltammetry (DPASV) are employed for determining
      simultaneously selenium, arsenic and copper, lead, cadmium, zinc, respectively,
      while mercury determination is carried out by the cold vapour atomic absorption
      spectrometry (CV-AAS) with reduction with SnCl2. The voltammetric measurements
      were performed using a conventional three-electrode cell and the ammonia-ammonium
      chloride buffer (pH 9.3) as supporting electrolyte. For all the elements, in
      addition to the detection limits, precision and accuracy data are also reported:
      the former, expressed as relative standard deviation (Sr), and the latter,
      expressed as relative error (e), are in all cases between 3 to 6%.

PMID- 11329771
TI  - Sea water contamination in underground waters of salento (Southern Italy).
AB  - In the present work, a study of a physico-chemical characterisation of
      underground waters, utilised for agriculture and human use in the Lecce district
      (Southern Italy) has been reported. The aim of the work has been to define the
      quality of underground waters in the different areas and to value salt
      contamination due to seawater intrusion. Statistical techniques, such as
      Principal Component Analysis (PCA) and Cluster Analysis (CA), have been utilised
      to examine the correlations among the different parameters and to define
      contamination areas. The results have shown a high salt contamination in artesian
      wells of the Ionian Sea coast.

PMID- 11329772
TI  - Thermodynamic and multinuclear magnetic resonance study of dimethyltin (IV)
      complexes with some imidazoles in aqueous solutions.
AB  - The interaction between imidazole (L1), 2-isopropylimidazole (L2), 2-amino
      benzimidazole (L3) and 2-(2-pyridyl)benzimidazole (L4) (L in general), and
      dimethyltin chloride in water have been investigated at 25 degrees C and ionic
      strength of 0.1 M sodium nitrate using the potentiometric technique. The results
      showed the formation of 1:1 and 1:2 (organotin:ligand) complexes and the
      corresponding stability constants were determined. The effect of the pKa values
      of the respective ligands on the stability constants of its complex species was
      elucidated. The concentration distribution of the complexes in solution was
      evaluated. Also, their solid complexes of the general formula in diethylether
      dichloromethane, give 1:2 (organotin:Ligand) [(L)2 (CH3)2 SnCl2.zH2O][L = L1, z =
      0 and L = L2, z = 1] and 1:1 [L (CH3)2 SnCl2.zH2O][L = L3, z = 0 and L = L4, z =
      2]. The separated solid products were characterized by elemental analyses (C, H,
      N, Cl), IR, mass spectra, thermogravimetric analysis (TGA) and magnetic
      susceptibility. The participation of the ligand functional groups in bonding to
      the organotin (IV) was discussed. Conductivity and 1H-NMR spectra were used to
      confirm the behaviour of these complexes in solution.

PMID- 11329773
TI  - Binding of 1,2,4-benzenetricarboxylate by open chain polyammonium cations.
AB  - The interaction of some open chain polyammonium cations with 1,2,4
      benzenetricarboxylate was studied potentiometrically, at 25 degrees C. For all
      the investigated systems, the species ALHr(r-3) (r = 1,2 ... n + 2; n = number of
      aminogroups; A = amine; L = carboxylate) are formed. The stability of these
      complexes depends on charges in the polyammonium cation and in the carboxylic
      ligand, and for the reaction HiAi+ + HjL(j - 3) = ALHi + j(i + j - 3) we found a
      mean free energy contribution for salt bridge -delta G0 = 6.5 +/- 0.3 kJ mol-1 n
      1 (n = number of possible salt bridges). The results of this investigation are
      compared with those of similar systems. By considering also the tricarboxylic
      ligands citrate and 1,2,3-propanetricarboxylate, we found for their complexes
      with polyammonium cations a fairly close stability. Calculations performed
      including complexes formed with these two ligands give -delta G0 = 6.6 +/- 0.4 kJ
      mol-1 n-1.

PMID- 11329774
TI  - Degradation of atrazine and several organophosphorus pesticides in oranges.
AB  - The degradation of atrazine and four organophosphorus pesticides (chlorpyriphos,
      fenamiphos, methidathion and methyl-parathion) in oranges was studied. Oranges
      were immersed in a Milli-Q water solution spiked with 10 mg litre-1 of each
      pesticide for one day, allowing their adsorption on the orange peel. Then, the
      oranges were rinsed with Milli-Q water and left outdoors to expose them to
      natural ambient conditions for two weeks. In parallel, an aqueous solution
      containing 1 mg litre-1 of each pesticide was placed in a Pyrex flask, which was
      tightly closed, and exposed to the same ambient conditions. Both samples (orange
      peel and Milli-Q water) were analyzed periodically by gas chromatography coupled
      to a nitrogen-phosphorus detector. The pesticide degradation in both samples
      could be described using a first-order degradation curve. Half-lives varied from
      14.5 to more than 30 days in aqueous solution and from 2.3 to 4.1 days in oranges
      for organophosphorus pesticides, while those for atrazine were 3.1 days and 14.2
      days, respectively. The presence of some organophosphorus degradation products in
      water samples after storage under the above conditions was confirmed by gas
      chromatography-mass spectrometry.

PMID- 11329775
TI  - [5-fluorouracil and dihydropyrimidine dehydrogenase].
AB  - Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme in
      the (fluoro) pyrimidine catabolic pathway, and has an important role in 5
      fluorouracil (5-FU) pharmacology. Some studies have demonstrated that the
      fluoropyrimidine catabolite may be related to the toxicity of 5-FU, and tumoral
      DPD prescribes the response to 5-FU-based therapy. By controlling DPD activity, a
      new class of fluorinated pyrimidines have been developed to minimize the
      variability of 5-FU pharmacodynamics, to decrease 5-FU toxicity, and improve its
      efficacy. Recently, these drugs, referred to as DIFs (DPD inhibitory
      fluoropyrimidines), have brought us to a new era of oral 5-FU therapy. The
      importance of DIF in 5-FU-based therapy is reviewed herein.

PMID- 11329776
TI  - [Prognostic factors for head and neck cancer].
AB  - Smoking, alcohol and chronic stimulation of the teeth are acknowledged as
      determinants of the risk for head and neck squamous cell carcinoma (H&NSCC)
      through the loss or mutation of tumor suppressor genes. Despite diagnostic and
      therapeutic advance, the overall prognosis of H&NSCC remains poor except for
      laryngeal cancer. Although the prognosis of H&NSCC depends primarily on
      clinicopathological factors (ex. TNM), the predictive value has been limited for
      the identification of patients with high risk of disease relapse. Recently, the
      analysis of DNA, oncogen amplification, and protein expression have been used in
      attempts to identify a new prognostic indicator for the evaluation and selection
      of optimal cancer treatment. Here, I review the literature on prognostic factors
      including chromosomes, cell cycle, apoptosis, angiogenesis, cytokines and
      adhesion molecules for patients with H&NSCC.

PMID- 11329777
TI  - [Role of Chemotherapy in head and neck cancer].
AB  - For head and neck cancer, a recent meta-analysis of published randomized trial
      results showed that concurrent chemoradiotherapy, adjuvant chemotherapy and
      neoadjuvant chemotherapy may increase absolute survival by 12.1%, 6.5%, and 3.7%,
      respectively. Initial response rates to first line chemotherapy are high, but
      this responsiveness does not appear to translate into a survival benefit. Thus,
      chemotherapy can be indicated as the standard therapy for a very limited range of
      advanced head and neck cancers. With the aim of prolonging survival, N stage
      advanced nasopharyngeal cancer is a good candidate for neoadjuvant chemotherapy.
      Among a large number of randomized trials of neoadjuvant chemotherapy, organ
      function preservation studies showed the possibility of laryngeal preservation
      for locally resectable T2 and T3 laryngeal and hypopharyngeal cancer. Concurrent
      chemoradiotherapy may be indicated for advanced T stage head and neck cancers,
      especially those with locally unresectable lesions. For N stage advanced
      pharyngeal cancer patients, adjuvant chemotherapy with applied after the standard
      therapy has a role in the treatment. With palliative treatment in advanced and/or
      recurrent disease, there is less benefit from chemotherapy and indications for
      chemotherapy should be selected for individual patients.

PMID- 11329778
TI  - [Chemoprevention and FAR therapy regimen comprised of 5-fluorouracil, vitamin A
      and radiation].
AB  - Retinoid is one of the most promising substances for chemoprevention and anti
      cancer effect. Retinoid has the following reported actions: induction of cell
      differentiation, control of cancer growth, repair of the precancerous lesion,
      prevention of the secondary carcinogenesis, control of angiogenesis and
      prevention of metastasis, and immunostimulation. In the present study, retinoid
      modified the cell cycle, reinforced the G1 check mechanism which is lost in
      cancer cells and induced apoptosis. Retinoid augmented the membrane permeability
      of anti-cancer drugs such as 5-FU, and reduced the exocytosis of anti-cancer
      drugs by suppressing the expression of the transport protein cMOAT. Retinoid also
      suppressed the invasive growth of the cancer cells. With the FAR therapy regimen
      (5-FU and retinil palmitate with radiation) and subsequent surgery, the disease
      specific five-year survival rate was close to 50% in various head and neck
      cancers. Thus, the chemoprevention and anti-cancer effects of retinoid may play
      an important role in the preservation of organs and QOL.

PMID- 11329779
TI  - [Cancer immunotherapy in head and neck region].
AB  - There is no one common immunotherapy for the treatment of head and neck cancer
      (H&N cancer). A streptococcal agent, OK-432, which is classified as a biological
      response modifier (BRM), is occasionally used by means of local administration
      for recurrent H&N cancer, and the response rate is approximately 18%. In regard
      to specific immunotherapy, a murine monoclonal antibody (named mAb 225) against
      the epidermal growth factor receptor (FGFR) that is frequently overexpressed in
      H&N cancer has been produced in the U.S.A. Furthermore, to obviate human anti
      mouse antibody responses, a chimeric human-to-murine version of mAb 225 (C225)
      was developed by exchanging the constant regions of mAb 225 to counterparts in
      human immune globulin. Phase I clinical trials of C225 in the U.S.A. demonstrated
      that treatment with C225 was well tolerated and that C225 given in combination
      with cisplatin has biologic activity. On the other hand, many tumor antigens
      recognized by cytotoxic T lymphocytes (CTL) have been identified from a variety
      of malignant tumors and some of them, including the MAGE-3 antigen, are
      frequently expressed in H&N cancer. We identified an MAGE-3-derived epitope
      recognized by HLA-A24-restricted CTL from peripheral blood mononuclear cells
      (PBMC). In contrast we failed to generate CTL specific for MAGE-3+/HLA-A24+
      tumors from PBMC in any of 5 HLA-A24+ cancer patients whose tumors expressed the
      MAGE-3 gene. Therefore, we did not apply MAGE-3-derived CTL epitope in clinical
      uses such as peptide vaccine and peptide pulsed dendritic cell infusion for H&N
      cancer.

PMID- 11329780
TI  - [Development of new treatment modalities for advanced head and neck carcinomas].
AB  - In most new cases of head and neck squamous cell carcinoma, especially in the
      pharynx and oral cavity, the tumors are advanced. Multidisciplinary treatments
      including chemotherapy in addition to definitive treatments, e.g., surgery and/or
      radiotherapy, have been applied. However, these treatments have not improved the
      poor prognosis for advanced head and neck carcinomas. A new curative treatment
      modality including chemotherapy and having a high complete response rate, e.g., a
      regimen consisting of taxanes, CDDP and 5-FU, is desirable. In addition, new
      therapeutic drugs against malignant solid tumors have been developed. The
      literature on thymidylate synthase inhibitor, dihydropyrimidine dehydrogenase
      inactivator, p-glycoprotein inhibitor, anti-epidermal growth factor receptor
      antibody, antiangiogenic drugs, COX-2 inhibitor and retinoids that may be applied
      in cases of head and neck carcinoma in the future, are reviewed.

PMID- 11329781
TI  - [Phase I study of amrubicin hydrochroride (SM-5887) for superficial bladder
      cancer in intravesical chemotherapy].
AB  - A phase I study of intravesical chemotherapy with amrubicin hydrochloride for
      superficial bladder cancer was conducted. Amrubicin was dissolved in 30 ml of
      physiological saline and injected intravesically on 6 consecutive days. The drug
      solution was retained for 2 hours. The starting dose was 60 mg/day, and the dose
      was escalated to 150 mg/day in 30 mg/day increments. Fifteen patients were
      entered into this study, of whom 14 were eligible and assessable for toxicity,
      and 13 were assessable for efficacy. The incidence and severity of cystic
      irritabilities such as micturition pain, pollakisuria and hematuria were related
      to the doses of amrubicin. At 150 mg/day, one of three patients experienced grade
      3 micturition pain and pollakisuria. The dose-limiting toxicities, therefore,
      were micturition pain and pollakisuria, and the maximal tolerated dose was
      estimated to be 150 mg/day, considering that none of the three patients could
      retain the drug solution for 2 hours. One complete response and four partial
      responses were obtained in 13 assessable patients, and the overall response rate
      was 38.5%. A breakdown according to the doses was as follows. One PR of 3
      patients were achieved at 60 and 90 mg/day, respectively 2 PRs of 5 patients at
      120 mg/day, and one CR of 2 patients at 150 mg/day.

PMID- 11329782
TI  - [Early phase II study of amrubicin (SM-5887) for superficial bladder cancer: a
      dose-finding study for intravesical chemotherapy].
AB  - An early phase II study (dose-finding study) of amrubicin hydrochloride for
      superficial bladder cancer was conducted. Amrubicin was dissolved in 30 ml of
      physiological saline and injected intravesically for 6 consecutive days. The drug
      solution was retained for 2 hours. Patients were randomly assigned to four
      groups, which were administered amrubicin at doses of 30, 60, 90, and 120 mg/day,
      respectively. Of 65 patients registered in this study, 63 were eligible and
      assessable for toxicities, and 55 assessable for efficacy. The response rate at
      each dose level was 50.0% (7PRs/14 patients) at 30 mg/day, 53.3% (8 PRs/15) at 60
      mg/day, 61.5% (2 CRs + 6 PRs/13) at 90 mg/day, and 69.2% (2 CRs + 7 PRs/13) at
      120 mg/day, respectively. These data suggests that the efficacy was related to
      the doses of amrubicin. The major toxicities were cystic irritabilities, such as
      micturition pain, pollakisuria and hematuria. These toxicities were related to
      the doses of amrubicin. Their incidence and the severity were not high compared
      with those reported about other anthracyclines such as doxorubicin and
      epirubicin. The optimal dose of amrubicin was estimated to be 90 to 120 mg/day in
      the intravesical treatment for superficial bladder cancer once a day for 6
      consecutive days.

PMID- 11329783
TI  - [Dose finding study of paclitaxel and carboplatin for ovarian cancer (JKTB)].
AB  - We conducted a dose-finding study for combination therapy of paclitaxel (Taxol;
      TXL) and carboplatin (Paraplatin; CBDCA). TXL is a novel plant-derived anticancer
      agent that is a diterpene derivative possessing the taxane ring. The subjects
      were patients with ovarian carcinoma, who were evaluated by a modified Fibonacci
      method. The dosage of TXL was 150 to 180 mg/m2. CBDCA was administered by dose
      escalation from AUC = 4 to 7. The administration schedule was as follows. Pre
      medication was administered before TXL was given. TXL was then administered by
      intravenous infusion over 3 hours, followed by CBDCA. The dose of CBDCA was
      determined using the Calvert formula: [AUCX (GFR + 25)]. GFR was calculated with
      the Jelliffe equation. The non-hematological toxicities observed in 15 eligible
      cases were mainly grade 1, with no grade 3 or above, and no increase in severity
      was observed with stepping up. The hematological toxicities were grade 3
      leukopenia in 5 of 15 cases, neutropenia in 5 cases and thrombocytopenia in 0
      cases. No grade 4 toxicity was observed. The lowest counts of leukocytes and
      neutrophils were reached after 10.8 and 11.7 days, respectively. The toxicities
      were reversible in most cases with subsequent recovery. The above findings
      indicate that the recommended dosages for TJ therapy for Japanese ovarian cancer
      patients should be TXL 180 mg/m2 and CBDCA at a target of AUC = 6.

PMID- 11329784
TI  - [Preoperative chemotherapy for advanced colorectal carcinomas--comparison of
      histological effect between 5'-DFUR + leucovorin tablet and 5'-DFUR alone].
AB  - The authors analyzed the histological effect of preoperative chemotherapy for 62
      advanced colorectal cancer patients using resected specimens. Thirty-one patients
      in the 5'-DFUR + LV group received 800 mg/day of 5'-DFUR and 30 mg/day of
      leucovorin for 10-14 days just before the operations. Thirty-one patients in the
      5'-DFUR group received 5'-DFUR 800 mg/day during the same period. None of the
      patients in either group developed any side effects. The results of the
      histological examination showed the number of Grade 1a and 1b cases in the 5'
      DFUR + LV group was 22 (66.7%) and 5 (15.2%), respectively, and in the 5'-DFUR
      group 21 (65.6%) and 5 (15.6%). In the 5'-DFUR + LV group, 3 lesions showed Grade
      2 histological degeneration, while there were no such lesions in the 5'-DFUR
      group. However, our results did not demonstrate any statistical difference
      between the two groups (p = 0.25, U test).

PMID- 11329785
TI  - [Fundamental study of combination chemotherapy with THP, 5-FU and CDDP for human
      KB carcinoma cell line and its multidrug resistant cell line KB-C1--usefulness of
      treatment with 5-FU preceding CDDP].
AB  - This study was designed to investigate the usefulness of treatment with 5-FU
      preceding CDDP in combination chemotherapy with THP, 5-FU and CDDP. Using the
      human KB carcinoma cell line and its multidrug resistant cell line KB-C1, the
      difference in the antitumor effect due to the sequence of administration of CDDP
      and 5-FU (TCF or TFC) was examined on cultured cells and nude mouse tumor
      xenografts. When KB and KB-C1 were treated with THP (0.01 microgram/ml) on day 1,
      CDDP (0.05 microgram/ml) on day 2 or day 4 and 5-FU (0.25 microgram/ml) on day 3
      and 4 or day 2 and 3, TFC suppressed the cell proliferation more strongly than
      TCF (p < 0.05), though there was no difference between KB and KB-C1. In nude
      mouse xenografts, intraperitoneal administrations of THP (0.5 mg/kg) on day 1,
      CDDP (2 mg/kg) on day 2 or day 5, and 5-FU (10 mg/kg) on day 3-5 or day 2-4
      inhibited tumor growth more effectively in KB than in KB-C1. At three weeks
      postadministration, growth inhibition by TCF and TFC was 29.9% and 57.4% in KB
      and 25.2% and 49.8% in KB-C1, respectively. These results indicate that TFC was
      superior to TCF in cytocidal and antitumor effects for KB and KB-C1.

PMID- 11329786
TI  - [A case of docetaxel-resistant breast cancer responsive to paclitaxel therapy].
AB  - A 73-year-old woman underwent docetaxel therapy for lung metastasis from breast
      cancer after having received CAF therapy. Because of the progressive disease due
      to secondary resistance to docetaxel, the patient was given three courses of
      paclitaxel therapy (60 mg/m2, day 1, 8, 15 and 22, repeated every 6 weeks). The
      paclitaxel therapy brought about no adverse effects and a 51%-reduction in the
      size of the metastatic lung tumor (PR). Although the duration of the response to
      the paclitaxel therapy was limited to about one month due to progression of a
      brain metastasis, paclitaxel therapy may be effective against docetaxel-resistant
      breast cancer.

PMID- 11329787
TI  - [A case of inoperable advanced gall bladder cancer responding to intra-arterial
      infusion of 5-fluorouracil (5-FU) and leucovorin (LV)].
AB  - The prognosis in cases of inoperable advanced gall bladder cancer is poor. We
      report here a case of inoperable advanced gall bladder cancer that responded to
      treatment with continuous intra-arterial infusion of 5-FU and bolus injection of
      LV for biochemical modulation. The patient was an 81-year-old woman, who visited
      a nearby clinic with the chief complaints of general fatigue and right lateral
      abdominal pain. A mass lesion which occupied from the dorsal surface of the liver
      to the pancreatic head was found by ultrasonography, and she was referred to our
      hospital for further diagnosis and therapy. The diagnosis was advanced gall
      bladder cancer of Stage IVa (S2, N3, P0, H0, Hinf1, Dinf1). For the selective
      arterial infusion of anticancer drugs, the patient underwent intra-arterial
      cannulation into the common hepatic artery, with a connecting subcutaneous port
      for arterial infusion therapy. The treatment schedule for 5-FU and LV therapy
      consisted of continuous infusion of 5-FU of 333 mg/m2 for 72 hr and bolus
      injection of LV of 20 mg/m2 3 times at 24 hr intervals. This treatment was
      repeated every 2 weeks. No side effects were observed after the first
      administration during hospitalization, so the treatment was continued up to 17
      times on an outpatient basis. A tumor response was seen in the primary lesion,
      No. 8 and No. 16 lymph node metastases. A partial response was observed for 13
      months and the overall survival was 15 months. These findings may imply that
      treatment with intra-arterial infusion of 5-FU and LV can be an effective
      chemotherapy for prolongation of survival in patients with inoperable advanced
      gall bladder cancer.

PMID- 11329788
TI  - [A case of successful management of nonresectable pancreas cancer with liver
      metastasis by intra-arterial infusion chemotherapy with angiotensin-II and
      administration of tegafur/uracil].
AB  - Nontypical chemotherapy regimens exist for advanced pancreatic cancer. We herein
      report a 62-year-old man whose nonresectable pancreatic cancer was treated
      effectively with a new method of intra-arterial regional chemotherapy with
      angiotensin-II (AT-II). The patient was admitted to our hospital with obstructive
      jaundice and anorexia. He was diagnosed as having inoperable advanced pancreatic
      cancer with liver metastasis. Enteric-coated tegafur/uracil (400 mg) was
      administered for 3 weeks. Simultaneously, intraarterial infusion with 5
      fluorouracil (500 mg) and infusion of methotrexate (100 mg) with 50 micrograms of
      AT-II was given every week. A catheter connected to a subcutaneously implanted
      port system was placed into the common hepatic artery. As a result of this
      treatment, the maximum diameter of the pancreatic tumor decreased from 3 cm to 2
      cm on the CT-scan. Serum carbohydrate antigen 19-9 (CA19-9) decreased from 24,000
      U/ml to 186 U/ml. Moreover, the performance status of patient also improved, and
      he was discharged from our hospital despite his terminal cancer. This regimen
      could well be effective in cases of advanced pancreatic cancer.

PMID- 11329789
TI  - [Curative resection of advanced gastric cancer responding to preoperative
      chemotherapy--a case report].
AB  - A 56-year-old male was admitted for treatment of advanced gastric cancer. The
      patient was diagnosed as having an unresectable advanced gastric cancer because
      cancer cells had invaded the pancreas head and there were metastatic lymph nodes.
      The patient underwent preoperative chemotherapy (FLEP: intra-arterial infusion of
      CDDP, ETP and intravenous infusion of 5-FU, LV). The primary tumor and metastatic
      lymph nodes were reduced by three course of chemotherapy. The patient underwent
      curative resection and survived without recurrence for 14 months after operation.
      Preoperative chemotherapy using FLEP was performed in 15 patients with
      unresectable primary advanced gastric cancer. This therapy resulted in
      significantly higher survival times. In conclusion, FLEP has been shown to be
      effective for unresectable advanced gastric cancer.

PMID- 11329790
TI  - [Chemotherapy by combination of low-dose CPT-11 and PSK in an elderly man with
      liver metastasis from gastric cancer].
AB  - We attempted a new regimen of low-dose CPT-11 and PSK against a high age man with
      liver metastasis from gastric cancer. CPT-11 was administered at 20 mg/m2/day x
      2/week, and PSK was given orally 3.0 g/day daily, respectively. Serum CEA level
      decreased gradually and almost reached normal limits (130 to 3.0 ng/ml). The
      tumor was reduced more than 50% at 13 weeks after the start of chemotherapy, when
      it had been continued for more than 8 weeks. There were no adverse effects and
      this regimen has been continued for more than 20 weeks without missing a week.
      These results suggest that the combination of low-dose CPT-11 and PSK has fewer
      side effects even in an elderly patient and may induce not only tumor shrinkage
      but also a prolonged time to progression.

PMID- 11329791
TI  - [Effective combination chemotherapy for a recurrent case of carcinoma of the
      remnant stomach].
AB  - A 69-year-old-man underwent distal gastrectomy for gastric carcinoma in 1988.
      Another gastric carcinoma was discovered in the remnant stomach in March 1995.
      Total gastrectomy and lymph node dissection were performed. CEA was up and we
      detected a big left suprarenal mass by abdominal CT. Suprarenalectomy was
      performed in June 1997. The swelling of lymph nodes was detected by CT and CEA
      was up to 1,000. Combination chemotherapy with intermittent 5-fluorouracil (5-FU)
      and low-dose cisplatin (CDDP) was performed. CEA suddenly decreased and lymph
      node swelling was reduced.

PMID- 11329792
TI  - [A case of recurrent gastric cancer successfully treated with TS-1].
AB  - A patient with recurrent gastric cancer which infiltrated the pelvic muscle after
      the treatment of paraaortic lymph node and ovarian metastases was successfully
      managed by a novel oral anticancer drug, TS-1. TS-1 was administered at a dose of
      80 mg/day. One course consisted of two repetitions of consecutive administration
      of TS-1 for 14 days and withdrawal of TS-1 for 14 days. Adverse reactions were
      mild and the patient did not request hospitalization after two courses had been
      completed. Subjective symptoms such as difficulty in walking improved after one
      week and a partial response was obtained after 2 weeks of treatment. At the end
      of 4 courses we could remove an indwelling pyelocatheter for the ureter
      stricture. As of 14 months after the beginning of administration of TS-1, the
      patient is being treated as an outpatient and has attained a better QOL than
      before.

PMID- 11329793
TI  - [Metastatic liver tumor arising from prostate cancer following transurethral
      resection of the prostate--a report of two cases].
AB  - We herein present a report of metastatic liver tumor arising from prostate cancer
      following transurethral resection of the prostate (TUR) in two patients. The two
      patients were diagnosed as having moderately differentiated prostate
      adenocarcinoma, either stage C or B2, and underwent hormonal and/or radiation
      therapy. TUR was performed due to the patients' complaints of urinary outlet
      obstruction. Liver metastasis, without evidence of bone or pulmonary metastasis,
      was then noted 23 and 5 months later in the patients with stage C and B2 prostate
      cancer, respectively. It is possible that the process of TUR is related to the
      release of tumor cells from the prostate into the systemic circulation and
      involved in the development of liver metastasis.

PMID- 11329794
TI  - [Development of a novel aromatase inhibitor, anastrozole (Arimidex)--its basic
      and clinical studies].
AB  - Anastrozole (JAN), developed by Zeneca UK (presently AstraZeneca UK), is a new
      aromatase inhibitor which belongs to triazole. Anastrozole shows selective
      aromatase inhibition and negligible effects on other steroid hormone
      biosyntheses. The daily dose of 3 mg/kg anastrozole inhibited the growth of DMBA
      mammary tumours significantly. Anastrozole inhibited the tumor growth at 5
      micrograms/mouse/day (s.c.) in androstenedione-treated ovariectomized nude mice
      inoculated with MCF-7CA cells transfected with aromatase gene. In the Japanese
      Phase IIa study, the response rate was 27.8% (10/36) in the 0.5 mg group, and
      38.2% (13/34) in the 1 mg group. The most common adverse drug reactions were
      leucopenia in the 0.5 mg group, and LDH increased and leucopenia in the 1 mg
      group. There were no early deaths, other serious adverse events, or adverse drug
      reactions of grade 3 or above in this trial; anastrozole was well tolerated. In
      the Japanese Phase IIb study, the response rates were 33.3% (117/351 patients)
      and 32.8% (114/348 patients) for anastrozole and tamoxifen, respectively, showing
      non-inferiority of anastrozole. The median time to disease progression (TTP) was
      251 days and 252 days for anastrozole and tamoxifen, respectively. Group
      comparison using a Cox regression model revealed non-inferiority of anastrozole.
      Therefore, anastrozole was found to be at least as effective as tamoxifen (in the
      response rate and TTP). In US study compared anastrozole with tamoxifen, TTP with
      anastrozole is a significantly longer than that of tamoxifen (p = 0.005, two
      sides). Anastrozole has shown to be at least as effective as tamoxifen, standard
      endocrine therapy for breast cancer, with good safety profiles. Thus, anastrozole
      is a promising first-line endocrine therapy in the treatment of postmenopausal
      breast cancer.

PMID- 11329795
TI  - [Tumor markers for endocrine neoplasms].
AB  - Tumor markers for thyroid neoplasms include thyroglobulin, calcitonin, and CEA.
      Thyroglobulin is particularly useful in discriminating follicular carcinoma from
      its benign counterparts. The measurement may also be helpful in the postoperative
      follow-up of patients with either follicular carcinoma or papillary carcinoma.
      Measuring plasma calcitonin and CEA is essential in the diagnosis and
      postoperative management of patients with medullary carcinoma. Highly specific
      genetic tests may become an alternative strategy in cases of familial medullary
      carcinoma. No specific tumor markers are available for parathyroid carcinoma;
      however, clinical characteristics provide diagnostic clues.

PMID- 11329796
TI  - Failings in treatment advice, SPCs and black triangles.
AB  - When Drug and Therapeutics Bulletin reviews a new medicine, one of our sources of
      information is the summary of product characteristics (SPC). This legal document
      provides advice about the product, including its unwanted effects and how these
      might be avoided. When referring to a new medicine, we include a [symbol: see
      text] in the text (see page 30, this issue). The Committee on Safety of
      Medicines/Medicines Control Agency (CSM/MCA) asks that this symbol be used to
      indicate when healthcare professionals should use a 'Yellow Card' to report any
      suspected adverse reaction. Here, we present evidence of weaknesses in the safety
      aspects of the SPC system and accompanying flaws in the Black Triangle Scheme.

PMID- 11329797
TI  - Drug treatment of genital chlamydial infection.
AB  - Chlamydia trachomatis is a common cause of genital infection. Although usually
      asymptomatic, the infection may have serious consequences, especially in women.
      Here, we review antibacterial therapy for adults with early chlamydial infections
      of the lower genital tract, to help prevent more serious complications.

PMID- 11329798
TI  - Can [symbol: see text] verteporfin help in macular degeneration?
AB  - Age-related macular degeneration (AMD), a disorder affecting older people, is the
      commonest cause of severe visual impairment in the UK. It involves degeneration
      of the central retina (the macula) that results in diminished capacity for
      detailed visual tasks, such as reading, writing and recognising faces. For most
      people with AMD there is no effective treatment. [symbol: see text]Verteporfin
      (Visudyne--Novartis Ophthalmics) was licensed last year for use in conjunction
      with laser activation (photodynamic therapy) for the treatment of "age-related
      macular degeneration in patients with predominantly classic subfoveal
      neovascularisation". Here, we review the place of this treatment.

PMID- 11329799
TI  - Detoxification of aqueous zinc using fluorapatite--bearing lean grade rock
      phosphate.
AB  - Detoxification of aqueous zinc was studied using the adsorption technique by
      application of fluorapatite bearing low grade phosphate as a sorbent. The effects
      of particle size of adsorbent, contact time, initial concentration of zinc and
      temperature on the adsorption process were studied. Initial rate of adsorption of
      zinc increases with time up to 30 min and thereafter it reaches equilibrium.
      Percent adsorption is adversely affected by increase in initial concentration of
      zinc and increase in particle size of sorbent. Adsorption processes follow first
      order kinetics and are found to be exothermic.

PMID- 11329800
TI  - Electrochemical oxidation of leachate pretreated in an upflow anaerobic sludge
      blanket reactor.
AB  - This study was conducted to develop a two-stage process for the treatment of Hong
      Kong leachate. The leachate, containing 4750 mg l-1 of chemical oxygen demand
      (COD) and 1310 mg l-1 of ammoniacal nitrogen (NH3-N), was first treated in a UASB
      (upflow anaerobic sludge blanket) reactor at 37 degrees C. The process removed on
      average 66.1% of COD with 6.1 days of hydraulic retention time (HRT),
      corresponding to an organic loading rate of 0.78 g-COD (l.day)-1. The UASB
      effluent, which had an average pH of 8.9, COD of 1610 mg l-1 and NH3-N of 1480 mg
      l-1, was then further treated by electrochemical oxidation in a batch reactor
      with recirculation. With the addition of 2000 mg l-1 of chloride (in the form of
      sodium chloride) and at a current density of 32.3 mA cm-2, 87% of COD and 100% of
      NH3-N were removed from the UASB effluent in six hours. The energy consumption
      was < 55 kWh kg-COD-1. The final effluent contained no residual NH3-N and only
      209 mg l-1 of COD.

PMID- 11329801
TI  - Ultrasonic irradiation for blue-green algae bloom control.
AB  - A novel application of ultrasonic irradiation for rapid control of blue-green
      algae (BGA) bloom was investigated. Potassium iodide (KI) experiments
      demonstrated that frequency and input power are the major factors that affect the
      ultrasonic irradiation intensity. Short exposure (3 s) to ultrasonic irradiation
      (120 W input power, 28 kHz) effectively settled naturally growing BGA suspension.
      Electron microscopy reconfirmed that sedimentation was caused by the disruption
      and collapse of gas vacuoles after ultrasonic exposure. Moreover, even after 5
      min of exposure to ultrasonic irradiation (1200 W input power, 28 kHz) the
      microcystin concentration in BGA suspensions did not increase. For the same input
      power (120 W), a lower frequency (28 kHz) was found to be more effective in
      decreasing the photosynthetic activity of BGA than a higher frequency (100 kHz).
      The sonicated cells did not proliferate when they were cultured in conditions
      that simulated the bottom of water bodies (i.e. with limited light (400 lx) or no
      light and non-aerated or aerated (1 l min-1)). Furthermore, ultrasonic
      irradiation did not only collapse gas vacuoles and precipitate BGA, but may have
      also inflicted damage on the photosynthetic system of the BGA.

PMID- 11329802
TI  - Phenols and aromatic hydrocarbons in chimney emissions from traditional and
      modern residential wood burning.
AB  - The emissions from a traditional tiled stove consisted mainly of lignin-related
      methoxyphenols with antioxidant properties, and 1,6-anhydroglucose from cellulose
      degradation. A wood stove of presently introduced energy-efficient design for
      residential heating and hot-water supply was shown to emit small amounts of
      methoxyphenols and anhydrosugars from primary wood pyrolysis. Secondary harmful
      components like benzene and polycyclic aromatic hydrocarbons constituted a major
      portion of the organic emissions. It is concluded that differences in smoke
      composition are essential to consider in recommendations and rules for proper
      choices of wood burning devices.

PMID- 11329803
TI  - Effect of operating parameters on anoxic biological phosphorus removal in
      anaerobic anoxic sequencing batch reactor.
AB  - Optimizing anoxic biological phosphorus removal in the anaerobic-anoxic
      sequencing batch reactor (A2 SBR) was observed to depend greatly on three
      parameters: the amount of added nitrate, the sludge retention time (SRT) and the
      phosphorus/carbon feeding ratio (P/C, wt/wt). The concentration of 120 mg N-NO3 l
      1 in the anoxic medium corresponding to 800 mg COD l-1 acetic acid and 60 mg P
      PO4 l-1 in the synthetic wastewater, the SRT of 15 days and the P/C feeding ratio
      of 20/100 were determined as optimal for complete phosphorus removal in the A2
      SBR. The acetate uptake, the phosphorus release and the phosphorus removal
      increased with the P/C feeding ratio and the phosphorus sludge content (Ps). The
      polyphosphate-accumulating organisms (PAO) were dominant under operation at all
      P/C feeding ratios tested except 2/100. At a P/C feeding ratio of 20/100, PAO
      could accumulate a high content of polyphosphate compared with other P/C ratios.
      In contrast, the P/C ratio of 2/100 caused a decrease in the polyphosphate
      content in PAO, the deterioration of enhanced biological phosphorus removal
      (EBPR) activity, and the dominance of glycogen-accumulating organisms (GAO). This
      study was completed by microscopic observations which revealed three
      morphological types of PAO. This is the first time that an oval form of PAO could
      be observed in the A2 SBR.

PMID- 11329804
TI  - Partial oxidation by ozone to remove recalcitrance from wastewaters--a review.
AB  - Xenobiotic organics produced by modern industrial processes resist conventional
      biological wastewater treatment. Ozone pretreatment to improve biodegradation via
      partial oxidation is a potential solution for this recalcitrance. Ozone forms no
      additional sludge, removes colour and has two modes of action that can be
      utilised according to the wastewater constituents. The preozonation of a variety
      of wastewaters and model compounds is reviewed here. Of the industrial processes
      examined, the associated recalcitrant organic compounds were generally
      halogenated heterocyclic or nitrogenous aromatics, aliphatic polymers or
      polyaromatics. Initial optimisation of ozone dose ensured the occurrence of
      partial oxidation, where over 90% parent compound transformation was required to
      give best results in the subsequent biological process. Ozonation intermediate
      and end-products included ketones, aldehydes and organic acids that were more
      biodegradable than the parent compounds. Biodegradability improvement was
      assessed using TOC, COD, BOD, BOD/COD ratio and OUR. Actual process feasibility
      and performance was evaluated using various combined ozonation-biodegradation
      trials; textile dying and finishing effluent being one area of application.
      Kinetic studies of chemical and biological stages facilitated process
      optimisation and can assist scale-up. The main factors affecting ozonation
      performance were pH, the nature and concentration of oxidisable organics, ozone
      dose, competition between the target compound and biodegradable by-products, the
      presence of oxidant scavengers, and the efficiency of ozone mass transfer. The
      formation of toxic or recalcitrant by-products has been found to occur in some
      cases, necessitating knowledge of wastewater constituents and trials on a site-by
      site basis.

PMID- 11329805
TI  - Seasonal variation in frequency of dividing cells of freshwater phytoplankters.
AB  - The frequency of dividing cells (FDC) of a natural phytoplankton community was
      studied seasonally in a freshwater pond to which water directly from Lake
      Kasumigaura was supplied. Phytoplankton samples were collected every 3 h at three
      depths (5, 30 and 75 cm) over 24 h periods in each of the four seasons and
      examined for FDC, cell size and abundance. Dominant phytoplankton species were
      Synedra ulna, Cyclotella kutzingiana, Chlamydomonas cingulata and Oscillatoria
      tenuis with Melosira italica, Cryptomonas ovata, and Synechococcus sp. being
      seasonally abundant. All species showed a similar FDC pattern related to the
      light-dark period that is a moderately phased division with the maximum FDC
      between 21:00-03:00.

PMID- 11329806
TI  - A sperm cell toxicity test procedure for the Mediterranean species Paracentrotus
      lividus (Echinodermata: Echinoidea).
AB  - This work describes the procedure developed in our laboratories for performing
      sperm cell toxicity tests using the autochthonous North Adriatic sea urchin
      Paracentrotus lividus Lmk. The procedure, derived from Dinnel (1987), was
      developed following the auto-ecological characteristics of P. lividus and in
      harmony with US Environmental Protection Agency standard procedures. Experiments
      conducted over a four-year period using copper as reference toxicant allowed the
      evaluation of method precision and intralaboratory reproducibility by different
      operators using organisms from different batches, in changing spatial (sampling
      sites) and temporal conditions (EC50 0.055 mg l.1 +/- 0.0081 SD; CV = 14.7%; n =
      25). These experiments with copper provided EC50 and NOEC data (0.032 +/- 0.008
      mg l-1). Results demonstrated the reliability of the method, as compared to other
      oceanic sea urchin species.

PMID- 11329807
TI  - [Influence of the earthworm Lumbricus terrestris on soil solution complexation
      capacity].
AB  - Four soil samples highly contaminated with metals of urban and mine origin (SE1,
      SE2, SM1, SM2) and having different physico-chemical proprieties were selected to
      study copper complexation capacity (LT) of soil solution. The effect of Lumbricus
      terrestris on copper complexation capacity of soil solution was investigated on
      SE1 and SE2. The complexation capacity was estimated by amperometric titration of
      soil solution by copper. Free hydrated cation and labile complexes of copper were
      determined by DPASV. The results show that the copper complexation capacity
      variation depends on the physico-chemical characteristics of soils, particularly
      pH. Thus, the values of copper complexation capacity are 0; 0.6 x 10(-7); 1.8 x
      10(-7) and 5.5 x 10(-7) mol l-1 respectively for SM2; SM1; SE1 and SE2 which are
      pH 5; 5.4; 6.5 and 7.4. Based on these results, the bioavailability levels of
      heavy metals show the following pool ranking: SM2 > SM1 > SE1 > SE2. The copper
      complexation capacity of soil solution increases with the soil disturbance by
      Lumbricus terrestris. This is more obvious when the time of disturbance by
      lumbrics is longer. Indeed, average values determined for 1 month and 3 months
      are 3.8 x 10(-7) and 7.8 x 10(-7) mol l-1 for SE1; 7.7 x 10(-7) and 15.2 x 10(-7)
      mol l-1 for SE2 respectively. It seems that the action of earthworm on soil can
      contribute to the decrease of bioavailability of heavy metals, particularly
      copper.

PMID- 11329808
TI  - Spatial distribution of microorganisms and measurements of oxygen uptake rate and
      ammonia uptake rate activity in a drinking water biofilter.
AB  - The biofilm characteristics (population dynamics and biofilm composition) in a
      biological filter for the removal of iron, manganese and ammonium were studied in
      a drinking water treatment plant. The objective was to examine the spatial
      distribution and biological composition of active biomass that grows in a
      biological filter and to verify the effect of the backwashing on the quantity of
      fixed biomass and on the density and activity of the biological population.
      Heterotrophic microorganisms activity was higher in the upper layer of the
      filter. Nitrifying microorganisms colonized the biofilter in a stratified manner
      and their activity was higher in the second layer of the filter. A total of 14
      species of ciliated protozoa and 7 species of filamentous microorganisms were
      found in the biofilters. Ciliates were concentrated in the filterbed layer in
      which the heterotrophic activity was higher. The grazing activity of ciliates on
      heterotrophic bacteria reduced the competition pressure on nitrifying
      microorganisms, supporting their growth and thus raising the ammonium removal
      efficiency. In general, filamentous microorganisms appeared to be indifferent to
      operating changes in the plant such as backwashing and filtering cycles.
      Crenothrix was the prevalent filamentous microorganism in terms of both frequency
      and abundance; it was found prevalently in the first layer where the oxidisation
      of iron and manganese occurred.

PMID- 11329809
TI  - Full scale UASB reactor performance in the brewery industry.
AB  - In this paper the 7 year experience of the Oriental Breweries, located in Kumi,
      Korea utilizing a full-scale upflow anaerobic sludge blanket (UASB) reactor for
      the anaerobic pretreatment of brewery wastewater is presented. The anaerobic
      pretreatment system selected has successfully achieved the desired treatment
      efficiency for the brewery wastewater during that period and it has also
      continued operation even with low wastewater concentrations (average CODcr 1,400
      mg l-1) and lower flow rates than specified by the design parameters. The CODcr
      removal of the UASB reactor averaged over 80% throughout the entire period,
      incurring normal running expenses of only $0.20-0.31 m-3 of treated water. In
      addition a further economical feature of the process was the utilization of the
      gas digester production as the municipal gas source, reducing total operating
      expenses around 30 to 45% and costing the plant only $0.1 m-3. Maintenance of
      good granule production, which is always a key issue in operating UASB systems,
      was not possible by this installation, however, so frequent expensive reseeding
      of the reactor was often necessary due to biomass washout. The full scale and lab
      scale research revealed that underloading can be as detrimental as overloading,
      due to excessively long retention time in the UASB system for the overall
      operating period and to excessive pre-acidification and/or incorrect reactor
      configuration of the completely mixed type. To enhance the sludge granulation,
      therefore, the installation of a pre-acidification reactor in the UASB system
      treating easily biodegradable substrates such as brewery wastewater is not
      necessary because adequate pre-acidification can occur in the equalization tank.

PMID- 11329810
TI  - Development of a case-based system for the supervision of an activated sludge
      process.
AB  - The development of a case-based reasoning system for the supervision of an
      activated sludge process is presented here. The methodology proposed permits the
      use of past experiences to solve new problems that arise in the process. These
      experiences are classified as cases or situations. The adaptation of cases and
      the generation of new cases are used to tune the response of the system and to
      learn from the new information generated by the process. The case and the case
      library definition, the initial seed, the search and retrieval process, the
      adaptation, the action, the evaluation and the learning steps are presented and
      outlined. The process studied is the wastewater treatment plant of Girona, Spain.
      Two examples of the response of the system to two different operational
      situations are presented. The paper also outlines the integration of different
      fields in a multidisciplinary approach as the most optimal solution to ensure the
      successful control and supervision of complex processes like the activated sludge
      process. With this aim the integration of an array of specific supervisory
      intelligent systems (for the logical analysis and reasoning) and numerical
      computations for detailed engineering is suggested.

PMID- 11329811
TI  - Going global with osteopathic medicine.

PMID- 11329812
TI  - Cranial rhythmic impulse related to the Traube-Hering-Mayer oscillation:
      comparing laser-Doppler flowmetry and palpation.
AB  - The primary respiratory mechanism (PRM) as manifested by the cranial rhythmic
      impulse (CRI), a fundamental concept to cranial osteopathy, and the Traube-Hering
      Mayer (THM) oscillation bear a striking resemblance to one another. Because of
      this, the authors developed a protocol to simultaneously measure both phenomena.
      Statistical comparisons demonstrated that the CRI is palpably concomitant with
      the low-frequency fluctuations of the THM oscillation as measured with the
      Transonic Systems BLF 21 Perfusion Monitor laser-Doppler flowmeter. This opens
      new potential explanations for the basic theoretical concepts of the physiologic
      mechanism of the PRM/CRI and cranial therapy. Comparison of the PRM/CRI with
      current understanding of the physiology of the THM oscillation is therefore
      warranted. Additionally, the recognition that these phenomena can be
      simultaneously monitored and recorded creates a new opportunity for further
      research into what is distinctive about the science and practice of osteopathic
      medicine.

PMID- 11329813
TI  - Researched and demonstrated: inquiry and infrastructure at osteopathic
      institutions.

PMID- 11329814
TI  - Non-Hodgkin's lymphoma in a patient with human immunodeficiency virus.
AB  - A 38-year-old woman with human immunodeficiency virus who was recently diagnosed
      with gastric ulcer presented to the hospital with nausea and vomiting of 1
      month's duration. Work-up of patient led to a diagnosis of diffuse, large B-cell
      non-Hodgkin's lymphoma. The patient underwent six cycles of chemotherapy, and
      repeated endoscopy and biopsy failed to reveal malignancy. She remains in
      remission 23 months posttreatment. Management of patients with human
      immunodeficiency virus and concurrent malignancy remains a challenge. The primary
      care physician plays a central role by collaborating with infectious disease and
      oncologist specialists to formulate a management plan.

PMID- 11329815
TI  - Cigarette smoking, hypertension and erectile dysfunction.
AB  - Smoking is associated with an increased risk of developing erectile dysfunction
      (ED). For example, in the Massachusetts Male Aging Study (MMAS), cigarette
      smoking amplified the risk of ED associated with other risk factors (e.g.
      hypertension, diabetes and dyslipidaemia) or with ageing. At the molecular level,
      several changes associated with smoking have been documented in man and
      experimental models. These changes could contribute to the pathogenesis of ED.
      Furthermore, studies performed in dogs demonstrated a smoking-related reduction
      in arterial flow and venous restriction. Similarly, impaired penile flow has been
      documented in men who smoke. Cigarette smoking also interferes with the
      effectiveness of intracavernous papaverine and PGEI. Quitting is the 'first-line'
      therapy of ED and one of the most important measures for the prevention of
      atherosclerosis.

PMID- 11329816
TI  - Diabetes, hypertension and erectile dysfunction.
AB  - Diabetes mellitus (DM) and hypertension are independent risk factors for erectile
      dysfunction (ED), macrovascular disease and microangiopathy. ED is very common
      among diabetic patients. Men with DM have ED at an earlier age and with a
      significantly higher prevalence (as high as 75%). The prevalence of DM also tends
      to be higher in patients with Peyronie's disease. DM impairs neurogenic and
      endothelium-mediated relaxation of penile smooth muscle. It is impossible to
      separate DM from hypertension and from the other vascular risk factors. Good
      glycaemic and hypertension control in diabetics is very important since these
      factors increase the risk of both microvascular and macrovascular complications,
      possibly including ED.

PMID- 11329817
TI  - Epidemiology, ultrasound and molecular biology in atherosclerosis--can we bridge
      the gaps?

PMID- 11329818
TI  - The molecular basis of penile erection.
AB  - Over the past two decades our understanding of the physiology and the various
      mediators involved in the pathway of penile erection has greatly increased. This
      has enabled us to develop effective pharmacological treatments for ED.

PMID- 11329819
TI  - Hypertension, stress and erectile dysfunction: potential insights from the
      analysis of heart rate variability.
AB  - Increased sympathetic activity and mental stress may affect erectile function.
      These effects may be acute and/or chronic. Cardiovascular regulation can be
      assessed non-invasively using a computer-based analysis of suitable haemodynamic
      signals. This research may provide new insights into the complex pathogenesis of
      erectile dysfunction (ED). In particular, there is still a largely unexplored
      area of research that covers the effect of drugs on these regulatory mechanisms.
      Such research may provide new therapeutic options.

PMID- 11329820
TI  - The treatment of hypertension in patients with erectile dysfunction.
AB  - Hypertension is another predictor of erectile dysfunction (ED). This is further
      evidence supporting a link between the pathogenesis of atherosclerotic disease
      and ED. In one study (TOMHS) involving hypertensive patients, the incidence of ED
      was 14.4%. The drugs used to treat hypertension may cause ED. However, there is
      little trial-based evidence to indicate which drugs are more likely to cause this
      side effect. In general, thiazide diuretics and beta-blockers seem to cause ED
      more often. In contrast, the alpha-blocker, doxazosin, has not been associated
      with an increased incidence of ED as a side effect. Doxazosin also improves
      urinary flow in patients with benign prostatic hyperplasia (BPH). This condition
      is common in elderly men as is hypertension and ED. Therefore, doxazosin may
      present a special advantage among this group of patients. This alpha-blocker
      would also be a good choice in patients with impaired glucose tolerance/diabetes
      because it improves insulin sensitivity. Moreover, ED and hypertension are more
      prevalent among diabetics. On a more speculative note, doxazosin may potentiate
      the therapeutic impact of specific treatments for ED.

PMID- 11329821
TI  - The anatomy, physiology and molecular pathways of vascular erectile dysfunction.
AB  - Vascular erectile dysfunction (VED) is composed of penile arterial insufficiency
      and veno-occlusive dysfunction. Both the arterial and venous dysfunctions are
      associated with cellular and molecular abnormalities. The goal of this work is to
      provide a summary of the gross anatomical and physiological abnormalities
      associated with VED and a theory of how these abnormalities result in VED based
      on the known molecular mechanism in cavernosal tissue and non-penile vascular
      tissue.

PMID- 11329822
TI  - Cardiovascular effects of oral pharmacotherapy in erectile dysfunction.
AB  - Several drugs have been developed to treat patients with erectile dysfunction
      (ED). In general, patients prefer orally administered drugs. The use of these
      drugs (e.g. sildenafil and apomorphine) is reviewed. Because ED is a common
      problem in men with vascular disease it is important to assess the effect of
      these drugs on the cardiovascular system. The safe use of these drugs in patients
      with vascular disease needs to be clearly established in appropriately designed
      trials.

PMID- 11329823
TI  - Sildenafil: a urologist's view.
AB  - Erectile dysfunction (ED) is a common problem with a multifactorial aetiology.
      The treatment of ED has been revolutionised by the introduction of
      intracavernosal injections some two decades ago. However, the recent development
      of the orally-administered drug sildenafil (Viagra) has had a major impact on the
      treatment of ED. We discuss the trials with sildenafil with special reference to
      cardiovascular risk factors associated with ED.

PMID- 11329824
TI  - Erectile dysfunction: intracavernous treatment.
AB  - The intracavernous use of papaverine, phentolamine and prostaglandin E1 (PGE1) is
      reviewed. The value of treatment combinations is also considered. In particular,
      the beneficial and harmful effects of long-term intracavernous treatment are
      considered. For example, the use of PGE1 may be associated with a long-term
      improvement of the penile microcirculation. In order to maximise the benefit from
      intracavernous therapy there is a need for specialised evaluations, a stepwise
      management approach and the consideration of patient preference.

PMID- 11329825
TI  - Benign prostatic hyperplasia and erectile dysfunction--is there a link?
AB  - There is little evidence to support a link between benign prostatic hyperplasia
      (BPH) and erectile dysfunction (ED). Any apparent relationship may reflect the
      fact that both are common conditions with a similar gender and age distribution.
      However, the surgical treatment of BPH (e.g. TURP or open prostatectomy) may
      cause ED as a postoperative complication in some patients. Similarly, the medical
      treatment of BPH with finasteride may be associated with ED (< 5% in one study).
      However, alpha-blockade is not associated with this side-effect.

PMID- 11329826
TI  - Vascular screening in andropause: non-invasive investigations in vascular disease
      screening.
AB  - Erectile dysfunction (ED) can be associated with atherosclerotic disease. It is
      therefore important to be able to evaluate the extent of arterial disease. This
      includes subclinical arterial disease. We have developed a score based on high
      resolution-B-mode ultrasound scanning of the carotid-femoral bifurcations. This
      is a cost-effective screening procedure that correlates well with the risk of
      cardiovascular events. The penile circulation can also be investigated to assess
      local circulation and the level of fibrosis. During this investigation it is
      worthwhile evaluating the carotid-femoral arteries because the risk factors that
      predict ED are the same as those for atherosclerosis. Penile fibrosis contributes
      to the pathogenesis of ED. Whether this change is associated with hypertension
      needs to be established by further studies.

PMID- 11329827
TI  - Microcirculatory studies in erectile disorders.
AB  - Local microcirculatory disturbances and fibrosis are thought to contribute to the
      pathogenesis of erectile dysfunction (ED). The assessment of these disturbances
      is now possible using non-invasive techniques such as laser Doppler flowmetry
      (LDF) and measuring transcutaneous pO2 and pCO2. However, these techniques need
      standardisation (e.g. in terms of equipment, conditions in which the examination
      is carried out and duration of measurement). Nevertheless, these techniques have
      a qualitative value. Marked alterations are seen in smokers and hypertensive
      patients. LDF has also been used to monitor the effect of treatment (e.g. after
      intracavernosal PGE1). These techniques remain non-diagnostic in individual
      patients. However, in groups of patients they may produce useful information
      (e.g. to assess treatments for ED).

PMID- 11329828
TI  - Erectile dysfunction and lipid disorders.
AB  - Epidemiological studies have shown that elevated serum cholesterol and reduced
      high density lipoprotein (HDL) cholesterol levels are associated with an
      increased risk of erectile dysfunction (ED). This is another example of the link
      between ED and atherosclerosis. Whether correcting a dyslipidaemic profile will
      result in a reduced risk of developing ED has not been established. Similarly, it
      is not known if such an intervention will improve symptoms in patients with
      established ED. The situation is further complicated by the likelihood that one
      of the rarer side-effects of fibrates and statins is ED. There is a need for
      appropriately designed trials to establish if intervening with statins or
      fibrates is beneficial on a short- or long-term basis for the treatment or
      prevention of ED.

PMID- 11329829
TI  - A 100 years of certitude? Social psychology, the experimental method and the
      management of scientific uncertainty.
AB  - For at least 100 years the experimental method has been used to add scientific
      rigour to the process of conducting social psychological research. More
      specifically, experiments have been used to reduce methodological uncertainty
      surrounding the causal relationships between variables. In this way the method
      has proved particularly useful in demonstrating the impact of social contextual
      variables over-and-above individual differences. However, problems with the
      method have arisen because over time experimentalists have tended (1) to define
      uncertainty too narrowly, (2) to emphasize uncertainty reduction, but (3) to
      neglect the equally important process of uncertainty creation. This has
      contributed to the normalization of social psychology as a science but also made
      the discipline more conservative and circumscribed. It is argued that
      experimentalists need to address broader metatheoretical and political
      uncertainties in order to rediscover the experiment's potency as a tool of
      revolutionary and progressive science.

PMID- 11329830
TI  - The perception of group variability in a non-minority and a minority context:
      when adaptation leads to out-group differentiation.
AB  - Minority and non-minority participants (Portuguese living in Germany vs. living
      in Portugal) completed open-ended measures of in-group and out-group perception.
      Participants' generated attributes were analysed to assess perceived group
      variability, complexity of group knowledge, language abstractness, first- or
      second-hand experience and participants' elaboration. Non-minority members
      perceived more out-group than in-group homogeneity (the 'outgroup homogeneity
      effect'), whereas minority members perceived more in-group than out-group
      homogeneity. This reversed pattern was owing to an increase in out-group
      differentiation by minority members and not to differences in in-group
      perception. Moreover, compared to majority members, minority members showed a
      greater elaboration and based their in-group and out-group knowledge more on
      personal beliefs derived from first-hand experience. These results are in accord
      with findings in migration research showing that in order to adapt, migrants
      develop a differentiated perception of the host culture. Conditions that lead
      group members to differentiate the out-group are discussed.

PMID- 11329831
TI  - Integrating social value orientation and the consideration of future consequences
      within the extended norm activation model of proenvironmental behaviour.
AB  - This study integrates social value orientation (Messick & McClintock, 1968) and
      the consideration of future consequences (CFC; Strathman, Gleicher, Boninger, &
      Edwards, 1994) within the extended norm activation model of proenvironmental
      behaviour (Stern, Dietz, & Kalof, 1993). A survey of college students (N = 161)
      revealed some preliminary support for the proposed model, using past and intended
      involvement in proenvironmental political behaviour as the primary outcome
      variables. Relative to proselfs, prosocials expressed stronger proenvironmental
      intentions and a stronger belief in the social consequences of environmental
      conditions. Relative to low CFCs, high CFCs expressed stronger proenvironmental
      intentions, greater involvement in proenvironmental behaviour, and a stronger
      belief in the personal, social and biospheric consequences of environmental
      conditions. Perceived consequences mediated the relationship between CFC and
      proenvironmental intentions and behaviour, and high CFCs evidence a stronger
      positive relationship between perceived social consequences and proenvironmental
      intentions.

PMID- 11329832
TI  - Two forms of intergroup discrimination with positive and negative outcomes:
      explaining the positive-negative asymmetry effect.
AB  - The minimal group paradigm is widely used for the study of intergroup
      discrimination. Reliably, group members show in-group favouritism in the
      allocation of positive outcomes but not in the allocation of negative outcomes.
      Less frequently investigated has been the withdrawal of positive and negative
      outcomes in the minimal paradigm. In this minimal group experiment the method of
      discrimination (allocation vs. withdrawal) and valence of outcomes (positive vs.
      negative) were combined in a 2 x 2 design (N = 57). Participants showed
      significant in-group favouritism only in the allocate (+) condition, less in
      withdrawal (-), and none at all in the remaining two cells (where parity
      predominated). Measures of subgroup and superordinate category identification
      paralleled these findings, and their inclusion as covariates in the analyses of
      favouritism and parity measures eliminated the previously significant
      interactions, thus implicating recategorization as the process mediating positive
      negative asymmetry effects in intergroup discrimination.

PMID- 11329833
TI  - 'This very difficult debate about Wik': stake, voice and the management of
      category memberships in race politics.
AB  - The issue of 'race' has assumed an extraordinarily salient position in Australian
      politics since the election of the conservative Howard government in 1996.
      Central to debate in the Australian policy has been the nature of the
      relationship between indigenous, or Aboriginal, Australians and the rest of the
      population, in particular over the issue of the land rights of indigenous people.
      Land rights, or 'native title', assumed a pre-eminent position in national
      political life in 1996/97 with the handing down by the High Court of the so
      called 'Wik judgment'. The discursive management of the ensuing debate by
      Australia's political leaders is illuminative of key sites of interest in the
      analysis of political rhetoric and the construction of 'racially sensitive'
      issues. Taking the texts of 'addresses to the nation' on Wik by the leaders of
      the two major political parties as analytic materials, we examine two features of
      the talk. First, examine how the speakers manage their stake in the position they
      advance, with an extension of previous work on reported speech into the area of
      set-piece political rhetoric. Second, in contrast to approaches which treat
      social categories as routine, mundane and unproblematic objects, we demonstrate
      the local construction of category memberships and their predicates as strategic
      moves in political talk. Specifically, we demonstrate how the categories of
      'Aborigines' and 'farmers', groups central to the dispute, are strategically
      constructed to normatively bind certain entitlements to activity to category
      membership. Furthermore, inasmuch as such categories do not, in use, reflect
      readily perceived 'objective' group entities in the 'real' world, so too
      'standard' discursive devices and rhetorical structures are themselves shown to
      be contingently shaped and strategically deployed for contrasting local,
      ideological and rhetorical ends.

PMID- 11329834
TI  - Social identification and gender-related ideology in women and men.
AB  - The nature of women's and men's gender-derived social identification was examined
      with a focus on the relationships between aspects of identity and gender-related
      ideology. Measures of social identification, sex-role ideology, and the
      perception of women's collective disadvantage were completed by 171 women and 91
      men who categorized themselves as either traditional, non-traditional or
      feminist. Factor analysis provided support for a multidimensional conception of
      gender-derived social identification, with viable subscales reflecting in-group
      ties, cognitive centrality, and in-group affect. For self-identified non
      traditional and feminist women, the cognitive centrality of gender was greater,
      and more consistently related to gender-related ideology, than for traditional
      women. Traditional men reported stronger in-group ties and more positive gender
      linked affect than did non-traditional men, but men's levels of identification
      were generally weakly related to gender-related ideology. The utility of
      considering both multiple dimensions and ideological correlates of group
      identification is discussed with reference to social identity theory.

PMID- 11329835
TI  - The role of desires and anticipated emotions in goal-directed behaviours:
      broadening and deepening the theory of planned behaviour.
AB  - Building on the theory of planned behaviour (TPB), we develop a new model of
      purposive behaviour which suggests that desires are the proximal causes of
      intentions, and the traditional antecedents in the TPB work through desires. In
      addition, perceived consequences of goal achievement and goal failure are
      modelled as anticipated emotions, which also function as determinants of desires.
      The new model is tested in two studies: an investigation of bodyweight regulation
      by 108 Italians at the University of Rome and an investigation of effort expended
      in studying by 122 students at the University of Rome. Frequency and recency of
      past behaviour are controlled for in tests of hypotheses. The findings show that
      desires fully mediated the effects of attitudes, subjective norms, perceived
      behavioural control and anticipated emotions on intentions. Significantly greater
      amounts of variance are explained in intentions and behaviour by the new model in
      comparison to the TPB and variants of the TPB that include either anticipated
      emotions and/or past behaviour.

PMID- 11329836
TI  - Constraints on equifinality: goals are good explanations only for controllable
      outcomes.
AB  - What makes a goal or a precondition a better explanation of an action or outcome?
      Recent research shows that whereas goals are preferred for common actions,
      preconditions are preferred for actions that require substantial resources,
      particularly when those actions are obstructed. Two studies examined whether
      judgments of goals and preconditions reflect the controllability of the events,
      and whether previous findings apply to events generated by participants.
      Participants judged goals and preconditions as explanations for desirable extreme
      and moderate events and assessed the controllability and probability of the
      events. For common events, goals were better explanations than preconditions,
      whereas for the extreme scenarios, preconditions were judged equal or better
      explanations. The extreme events were seen as less controllable than the moderate
      events, and the controllability of the events predicted judgments of goals as
      explanations. The results suggest that participants see goals as better
      explanations only for events that the person can control, and they judge
      preconditions to be good explanations for events where the person has little
      control. These findings suggest that equifinality may apply only to those actions
      and outcomes where the preconditions are readily obtainable.

PMID- 11329837
TI  - Introduction. Bayesian approaches to technology assessment and decision making.

PMID- 11329838
TI  - Can Bayesian methods make data and analyses more relevant to decision makers? A
      perspective from Medicare.
AB  - Decision making in health care has become increasingly reliant on information
      technology, evidence-based processes, and performance measurement. It is
      therefore a time at which it is of critical importance to make data and analyses
      more relevant to decision makers. Those who support Bayesian approaches contend
      that their analyses provide more relevant information for decision making than do
      classical or "frequentist" methods, and that a paradigm shift to the former is
      long overdue. While formal Bayesian analyses may eventually play an important
      role in decision making, there are several obstacles to overcome if these methods
      are to gain acceptance in an environment dominated by frequentist approaches.
      Supporters of Bayesian statistics must find more accommodating approaches to
      making their case, especially in finding ways to make these methods more
      transparent and accessible. Moreover, they must better understand the decision
      making environment they hope to influence. This paper discusses these issues and
      provides some suggestions for overcoming some of these barriers to greater
      acceptance.

PMID- 11329839
TI  - Using data to enhance the expert panel process. Rating indications of alcohol
      related problems in older adults.
AB  - OBJECTIVE: To enhance the validity of a well-known expert panel process, we used
      data from patient surveys to identify and correct rating errors. METHODS: We used
      the two-round RAND/UCLA panel method to rate indications of harmful (presence of
      problems), hazardous (at risk for problems), and nonhazardous (no known risks)
      drinking in older adults. Results from the panel provided guidelines for
      classifying older individuals as harmful, hazardous, or nonhazardous drinkers,
      using a survey. The classifications yielded unexpectedly high numbers of harmful
      and hazardous drinkers. We hypothesized possible misclassifications of drinking
      risks and used the survey data to identify indications that may have led to
      invalid ratings. We modified problematic indications and asked three clinician
      panelists to evaluate the clinical usefulness of the modifications in a third
      panel round. We revised the indications based on panelist response and reexamined
      drinking classifications. RESULTS: Using the original indications, 48% of
      drinkers in the sample were classified as harmful, 31% as hazardous, and 21% as
      nonhazardous. A review of the indications revealed framing bias in the original
      rating task and vague definitions of certain symptoms and conditions. The
      modified indications resulted in classifications of 22% harmful, 47% hazardous,
      and 31% nonhazardous drinkers. CONCLUSIONS: Analysis of survey data led to
      identification and correction of specific errors occurring during the panel
      rating process. The validity of the RAND/UCLA method can be enhanced using data
      driven modifications.

PMID- 11329840
TI  - Providing health information to women. The role of magazines.
AB  - OBJECTIVES: We were interested in health coverage in women's magazines in the
      United States and how it compared with articles in medical journals, women's
      health interests, and women's greatest health risks. METHODS: We examined 12
      issues of Good Housekeeping (GH) and Woman's Day (WD) and 63 issues of the New
      England Journal of Medicine (NEJM) and the Journal of the American Medical
      Association (JAMA). We tallied the most common health questions of women
      presenting to the University of Michigan's Women's Health Resource Center (WHRC)
      during the same period. RESULTS: Less than a fifth of the magazine articles dealt
      with health-related topics. Of those, a third dealt with diet, with the majority
      emphasizing weight loss rather than eating for optimal health. Few of the
      articles cited research studies, and even fewer included the name of the journal
      in which the study was published. In JAMA and NEJM, less than one-fifth of
      original research studies dealt with women's health topics, most commonly
      pregnancy-related issues, hormone replacement therapy, breast and ovarian cancer,
      and birth defects. At the same time, the most common requests for information at
      the WHRC related to pregnancy, fertility, reproductive health, and cancer.
      CONCLUSION: The topics addressed in women's magazines do not appear to coincide
      with the topics addressed in leading medical journals, nor with women's primary
      health concerns or greatest health risks. Information from women's magazines may
      be leading women to focus on aspects of health and health care that will not
      optimize risk reduction.

PMID- 11329841
TI  - Time costs associated with cervical cancer screening.
AB  - OBJECTIVES: Time costs borne by women when undergoing cervical cancer screening
      have rarely been elucidated, although such costs may pose substantial barriers to
      care. The purpose of this project was to quantify the opportunity costs
      associated with cervical cancer screening in young women attending Planned
      Parenthood Clinics. METHODS: We conducted a self-report survey of 105 women from
      six clinics to measure travel, waiting, and exam times associated with cervical
      cancer screening. Respondents recorded their time of arrival and departure,
      length of time in the waiting room, age, income level, and hours per week they
      worked outside of the home. Time costs were valued three ways: through self
      reported hourly wage, age- and gender-adjusted minimum earnings, and national age
      and gender-adjusted hourly wages. RESULTS: Respondents were on average 24 years
      old, worked 29 hours per week outside the home, and earned less than $20,000 per
      year. Mean time for one-way travel was 18.7 minutes; waiting room time was 16.9
      minutes; and exam time was 50.8 minutes. Time costs were estimated to be $14.08
      per visit based upon the self-reported hourly wage; $16.46 per visit based upon
      age- and gender-adjusted minimum earnings; and $19.63 per visit based upon age-
      and gender-adjusted national wage rates. CONCLUSIONS: Time costs associated with
      cervical cancer screening represent an important opportunity cost and should be
      considered in studies attempting to identify barriers to screening adherence. Our
      results indicate that time costs accounted for up to 25% of cervical cancer
      screening costs. Time costs should be identified, measured, valued, and included
      in cost-effectiveness analyses of cervical cancer screening.

PMID- 11329842
TI  - Using full probability models to compute probabilities of actual interest to
      decision makers.
AB  - The objective of this paper is to illustrate the advantages of the Bayesian
      approach in quantifying, presenting, and reporting scientific evidence and in
      assisting decision making. Three basic components in the Bayesian framework are
      the prior distribution, likelihood function, and posterior distribution. The
      prior distribution describes analysts' belief a priori, the likelihood function
      captures how data modify the prior knowledge; and the posterior distribution
      synthesizes both prior and likelihood information. The Bayesian approach treats
      the parameters of interest as random variables, uses the entire posterior
      distribution to quantify the evidence, and reports evidence in a "probabilistic"
      manner. Two clinical examples are used to demonstrate the value of the Bayesian
      approach to decision makers. Using either an uninformative or a skeptical prior
      distribution, these examples show that the Bayesian methods allow calculations of
      probabilities that are usually of more interest to decision makers, e.g., the
      probability that treatment A is similar to treatment B, the probability that
      treatment A is at least 5% better than treatment B, and the probability that
      treatment A is not within the "similarity region" of treatment B, etc. In
      addition, the Bayesian approach can deal with multiple endpoints more easily than
      the classic approach. For example, if decision makers wish to examine mortality
      and cost jointly, the Bayesian method can report the probability that a treatment
      achieves at least 2% mortality reduction and less than $20,000 increase in costs.
      In conclusion, probabilities computed from the Bayesian approach provide more
      relevant information to decision makers and are easier to interpret.

PMID- 11329843
TI  - Estimating the Bayesian loss function. A conjoint analysis approach.
AB  - Current health economic literature does not provide clear guidelines on how
      uncertainty around cost-effectiveness estimates should be incorporated into
      economic decision models. Bayesian analysis is a promising alternative to
      classical statistics for incorporating uncertainty in economic analysis.
      Estimating a loss function that relates outcomes to societal welfare is a key
      component of Bayesian decision analysis. Health economists commonly compute the
      loss function based on the quality-adjusted life-years associated with each
      outcome. However, if welfare economics is adopted as the theoretical foundation
      of the analysis, a loss function based in cost-benefit analysis (CBA) may be more
      appropriate. CBA has not found wide use in health economics due to practical
      issues associated with estimating such a loss function. In this paper, we present
      a method based in conjoint analysis for estimating the CBA loss function that can
      be applied in practice. We illustrate the use of the methodology using data from
      a pilot study.

PMID- 11329844
TI  - Bayesian value-of-information analysis. An application to a policy model of
      Alzheimer's disease.
AB  - A framework is presented that distinguishes the conceptually separate decisions
      of which treatment strategy is optimal from the question of whether more
      information is required to inform this choice in the future. The authors argue
      that the choice of treatment strategy should be based on expected utility, and
      the only valid reason to characterize the uncertainty surrounding outcomes of
      interest is to establish the value of acquiring additional information. A
      Bayesian decision theoretic approach is demonstrated through a probabilistic
      analysis of a published policy model of Alzheimer's disease. The expected value
      of perfect information is estimated for the decision to adopt a new
      pharmaceutical for the population of patients with Alzheimer's disease in the
      United States. This provides an upper bound on the value of additional research.
      The value of information is also estimated for each of the model inputs. This
      analysis can focus future research by identifying those parameters where more
      precise estimates would be most valuable and indicating whether an experimental
      design would be required. We also discuss how this type of analysis can also be
      used to design experimental research efficiently (identifying optimal sample size
      and optimal sample allocation) based on the marginal cost and marginal benefit of
      sample information. Value-of-information analysis can provide a measure of the
      expected payoff from proposed research, which can be used to set priorities in
      research and development. It can also inform an efficient regulatory framework
      for new healthcare technologies: an analysis of the value of information would
      define when a claim for a new technology should be deemed substantiated and when
      evidence should be considered competent and reliable when it is not cost
      effective to gather any more information.

PMID- 11329845
TI  - Why Bayesian analysis hasn't caught on in healthcare decision making.
AB  - The objective of this paper is to discuss why Bayesian statistics is not used
      more in healthcare decision making and what might be done to increase the use of
      Bayesian methods. First, a case is made for why Bayesian analysis should be used
      more widely. Serious weaknesses of commonly used frequentist methods are
      discussed and contrasted with advantages of Bayesian methods. Next, the question
      of why Bayesian methods are not used more widely is addressed, considering both
      philosophical differences and practical issues. Contrary to what some might
      think, the practical issues are more important in this regard. Finally, some
      steps to encourage increased use of Bayesian methods in healthcare decision
      making are presented and discussed. These ideas are straightforward but are by no
      means trivial to implement, largely because it is difficult to fight tradition
      and make major paradigm shifts quickly. The primary needs are improved Bayesian
      training at the basic level (which means textbooks and other materials as well as
      training of those who teach at the basic level), procedures to make Bayesian
      analysis easier to understand and use (better software and standard methods for
      displaying and communicating Bayesian outputs will help here), and the education
      of decision makers about the advantages of Bayesian methods in important
      healthcare decision-making problems.

PMID- 11329846
TI  - A Bayesian approach to stochastic cost-effectiveness analysis. An illustration
      and application to blood pressure control in type 2 diabetes.
AB  - The aim of this paper is to discuss the use of Bayesian methods in cost
      effectiveness analysis (CEA) and the common ground between Bayesian and
      traditional frequentist approaches. A further aim is to explore the use of the
      net benefit statistic and its advantages over the incremental cost-effectiveness
      ratio (ICER) statistic. In particular, the use of cost-effectiveness
      acceptability curves is examined as a device for presenting the implications of
      uncertainty in a CEA to decision makers. Although it is argued that the
      interpretation of such curves as the probability that an intervention is cost
      effective given the data requires a Bayesian approach, this should generate no
      misgivings for the frequentist. Furthermore, cost-effectiveness acceptability
      curves estimated using the net benefit statistic are exactly equivalent to those
      estimated from an appropriate analysis of ICERs on the cost-effectiveness plane.
      The principles examined in this paper are illustrated by application to the cost
      effectiveness of blood pressure control in the U.K. Prospective Diabetes Study
      (UKPDS 40). Due to a lack of good-quality prior information on the cost and
      effectiveness of blood pressure control in diabetes, a Bayesian analysis assuming
      an uninformative prior is argued to be most appropriate. This generates exactly
      the same cost-effectiveness results as a standard frequentist analysis.

PMID- 11329847
TI  - Bayesian cost-effectiveness analysis. An example using the GUSTO trial.
AB  - A desirable element of cost-effectiveness analysis (CEA) modeling is a systematic
      way to relate uncertainty about input parameters to uncertainty in the
      computational results of the CEA model. Use of Bayesian statistical estimation
      and Monte Carlo simulation provides a natural way to compute a posterior
      probability distribution for each CEA result. We demonstrate this approach by
      reanalyzing a previously published CEA evaluating the incremental cost
      effectiveness of tissue plasminogen activator compared to streptokinase for
      thrombolysis in acute myocardial infarction patients using data from the GUSTO
      trial and other auxiliary data sources. We illustrate Bayesian estimation for
      proportions, mean costs, and mean quality-of-life weights. The computations are
      performed using the Bayesian analysis software WinBUGS, distributed by the MRC
      Biostatistics Unit, Cambridge, England.

PMID- 11329848
TI  - Introduction to Bayesian reasoning.
AB  - Interest in Bayesian analyses has increased recently, in part as a response to
      policy makers wanting sound scientific bases for health technology assessments,
      and associated healthcare funding decisions. This paper provides a brief and
      simplified description of Bayesian reasoning. Bayes is illustrated in a clinical
      setting of an expert helping a woman understand the potential risk of passing on
      an inheritable disease (hemophilia) to her next child, based on disease
      occurrence in two living children. The illustration describes fundamental
      concepts and derivations, such as Bayes theorem, likelihood functions, prior
      probability, and posterior probability. A second illustration shows the use of
      Bayes for interpreting clinical trial results. The uncertainty in the clinical
      effect before and after the trial analyses has been completed is characterized by
      the Bayes prior and posterior probabilities, respectively. Techniques are also
      shown for estimating the potential loss (e.g., in lives lost) for making the
      wrong decision with and without knowledge of the trial results, an estimation
      that cannot be carried out using techniques of hypotheses testing associated with
      the frequentist school of statistics. Information from Bayes analysis then may be
      used to help policy makers decide, or justify, whether the analyses provides a
      sufficient basis for making a treatment recommendation, or whether there remains
      a need to request more information. Subsequent papers in this volume offer
      additional examples and clarification of the use of Bayes in clinical practice
      and in interpretation of clinical studies.

PMID- 11329849
TI  - An elementary introduction to Bayesian computing using WinBUGS.
AB  - Bayesian statistics provides effective techniques for analyzing data and
      translating the results to inform decision making. This paper provides an
      elementary tutorial overview of the WinBUGS software for performing Bayesian
      statistical analysis. Background information on the computational methods used by
      the software is provided. Two examples drawn from the field of medical decision
      making are presented to illustrate the features and functionality of the
      software.

PMID- 11329850
TI  - "Natural history" clinical trials: an enduring contribution to modern medical
      practice.

PMID- 11329851
TI  - Cyclooxygenase-2 inhibitors.

PMID- 11329852
TI  - Angiotensin-converting enzyme inhibitors.

PMID- 11329853
TI  - 5 alpha-Reductase inhibitors.

PMID- 11329854
TI  - Peroxisome proliferator-activated receptor (PPAR) gamma agonists for diabetes.

PMID- 11329855
TI  - Discovery and clinical development of HIV-1 protease inhibitors.

PMID- 11329857
TI  - Pure selective estrogen receptor modulators, new molecules having absolute cell
      specificity ranging from pure antiestrogenic to complete estrogen-like
      activities.

PMID- 11329856
TI  - Calcineurin inhibitors and the generalization of the presenting protein strategy.

PMID- 11329858
TI  - Monoclonal antibody therapy.

PMID- 11329859
TI  - Glucan synthase inhibitors as antifungal agents.

PMID- 11329860
TI  - HMG-CoA reductase inhibitors.

PMID- 11329861
TI  - Quality improvement to guide the new health system.
AB  - While there are many areas, such as intensive care treatment and pain management,
      where great gains in quality improvement can be made, the greatest strides will
      come as the leaders and trustees in health care organizations begin to create
      "the industrial revolution" in their organizations by creating cultures of
      quality. Stephen Shortell recommends the following list of things board members
      can do to improve quality in their organizations.

PMID- 11329862
TI  - Medicare trustees see near-term gain for hospital fund but long term pain for
      Medicare.

PMID- 11329863
TI  - Bush presents his plans for patients' rights legislation.

PMID- 11329864
TI  - Medicare to provide limited coverage of angioplasty of carotid artery with stent
      insertion for stroke.

PMID- 11329866
TI  - California Nurses Association announces proposal for minimum staffing rules.

PMID- 11329865
TI  - Proposed legislation would expand Medicare Pap test coverage.

PMID- 11329867
TI  - Prescription drug benefits more expensive than Bush and Democratic proposals.

PMID- 11329868
TI  - Non-invasive glucose monitoring device approved.

PMID- 11329869
TI  - [Genetic relationship among four Yunnan populations revealed by sequence of mtDNA
      D-loop].
AB  - mtDNA D-loop noncoding region 16048-16569 and the following 1-41 (563 bp) in 99
      individuals of four Yunnan ethnic minorities (Dai, Wa, Lahu and Tibetan) were
      sequenced and then a phylogenetic tree was reconstructed by Neighbor-Joining
      method. These 99 mtDNA lineages were classified into 3 genotype groups in the
      tree. All lineages with 9 bp deletion in the COII/tRAN(Lys) intergenic region
      were clustered in group I, some individuals of Dai, Lahu, Wa and only 2 Tibetan
      individuals clustered in group II, individuals of all four populations were
      included in group III. A phylogenetic tree of the four populations was
      constructed by NJ method on the basis of estimate of net genetic distance among
      them. Our results showed, the genetic distance among Dai, Wa and Lahu is very
      close, but far from Tibetan, their genetic distance is similar to their
      geographic distance. Although both as descendants of ancient Di-Qiang tribe in
      history and speaking similar language, Lahu and Tibetan are not closely related.
      This result indicates that there are different origins of these two populations.

PMID- 11329870
TI  - [Construction of chicken hypothalamus cDNA library and primary analysis of ESTs
      sequences from partial clones].
AB  - Using hypothalamus as material and lambda gt10 as vector, chicken hypothalamus
      cDNA library has been constructed. The results showed that the titration of the
      cDNA library we constructed was 3.8 x 10(6), and the fragment length of inserted
      DNA ranged mainly from 1.0-3.0 kb. The ESTs was sequenced and primarily analyzed
      for ten clones randomly selected from above library. After analysis with BLASTn
      and FASTA3.1, it was found that four ESTs developed matched homologous sequence
      in chicken, four also had similar sequences in human and other species, have
      other two sequences were function-unknown gene. The sequences of ten ESTs we
      studied have been loaded into GenBank.

PMID- 11329871
TI  - [Prokaryotic expression of recombinant grass carp growth hormone].
AB  - The recombinant plasmid containing a synthetic grass carp growth hormone cDNA was
      transformed into Escherichia coli BL21 (DE3) and expressed efficiently, induced
      by 1 mmol/L IPTG. 12.5% SDS-PAGE showed the molecular weight of new added protein
      in Escherichia coli BL21 (DE3) is consistent with that of grass carp growth
      hormone. The recombinant protein was composed of approximately 40% of the total
      bacterial proteins. The target protein was purified with Ni-NTA affinity column.
      Western-blotting conformed that recombinant protein could specifically react with
      antibody against grass carp growth hormone. ELISA-receptor assay showed the
      bioactivity of recombinant protein is consistent with that of nature grass carp
      growth hormone.

PMID- 11329872
TI  - [Generation of Mx-cre transgenic mice].
AB  - To generate the transgenic mice expressing cyclization recombination enzyme, the
      recombinant gene, in which the coding region of cre gene is derived by the
      promoter of mouse Mx gene, was microinjected into pronuclei of fertilized mouse
      eggs. Founders of transgenic mice harbouring the recombinant gene were screened
      by polymerase chain reaction (PCR) at genomic DNA level and confirmed by Southern
      blot. One line of Mx-cre transgenic mice was obtained. Then, the Mx-cre
      transgenic mouse line was cultured and propagated.

PMID- 11329873
TI  - [Genetic analysis on litter size in pigs].
AB  - Genetic analysis was conducted on the data of 3 populations with 1,686 litters
      including Erhualian pig, Large White and first cross. The results indicated that
      the heritability estimates for the total number of piglets born, the number of
      piglets born alive, the number of piglets at 20 d and at 45 d were 0.081, 0.156,
      0.402 and 0.419, respectively. The major gene index analysis indicated that the
      prolificacy of Erhualian pig was influenced by major genes.

PMID- 11329874
TI  - [Cloning, sequencing and chromosome location of Sry gene of Muntjak munticus
      vaginalis by DOP-PCR and microdissection].
AB  - We isolated 1, Y1, Y2 chromosomes of the male M.m vaginalis by microdissection
      and amplified the DNA copies by DOP-PCR. Using the DOP-PCR products of 1, Y1, Y2
      chromosomes of M.m vaginalis as template respectively and the primers designed
      within human SRY HMG box, the Sry gene of the male M.m vaginalis was amplified,
      and it was cloned and sequenced. It is proved that Y2 is the real sex chromosome
      in the male M.m vaginalis at molecular level for the first time, and Sry was
      localized on Y2 chromosome.

PMID- 11329875
TI  - [Analyses of chromosomal karyotypes and cytogenetic variations of animal cell
      lines].
AB  - After the master cell stock(mcs) and working cell bank of more than 30 different
      strains of 7 animal kidney cell lines (F-81 or CRFK cell line, MDCK cell line,
      Vero or Vero-2 cell line, MA-104 cell line and BHK-21 cell line) were established
      in China, the chromosomal number variations and structural aberrations of the
      above lines, primary feline or canine kidney cell (FKC or CKC) and HeLa cell line
      were investigated and their karyotypes of routine or Giemsa chromosomal bands
      were analyzed. The carcinogenesis or tumorigenicity testing of these cells in
      about 700 nude mice and for colony formation in soft agar (SA) and for
      agglutination under different concentration of plant lectins was carried out.
      Both tumorigenicity-negative strains of F-81, CRFK, Vero or Vero-2 lines and very
      low-tumorigenicity strains of MDCK line were successfully selected and evaluated
      for the production of canine or feline combination viral vaccines, which are free
      of infectious agents, and described with respect to cytogenetic characteristics
      and tumorigenicity. Rate of modal chromosome number represents the ratio of cell
      number having modal chromosome number to all the split cell number analyzed at
      random. Rate of difference represents the ratio of difference of the rate of
      modal chromosome number between mcs (master cell stock) + n and mcs passages. The
      chromosomal analysis results showed that the ratio of difference of the rate of
      modal chromosome number between mcs + n and mcs passages was not more than 5%-15%
      and the structure aberrations was generally 0%-3%, not more than 5%-10%, thus the
      hereditary character of cell lines is comparatively stable without significant
      difference between different passages. The genetic characteristics of chromosomal
      number of cell lines determines their tumorigenicity, but it is species specific.
      Experimental models were established for the researches on the prevention and
      prophylaxis of malignant tumors or cancers and their genetically biological
      characteristics. Tests showed that there was correlation among cell line
      chromosome number variations, anchorage independence in soft agar, agglutination
      under plant lectins and tumor-forming ability in nude mice. Since testing in
      vitro is more economic, simpler, faster, and is thought to be reliable, we
      recommend plant lectins followed by SA or analysis of karyotypes as the initial
      means for monitoring tumorigenicity of animal cell line in nude mice.

PMID- 11329876
TI  - [Amplification and analysis of T-DNA flanking sequences in transgenic rice].
AB  - Rice transformation mediated by Agrobacterium tumefaciens has technically matured
      to some extent, but the mechanics of T-DNA integration in transgenic rice remains
      largely unknown. Using thermal asymmetric interlaced PCR (TAIL-PCR), we analyzed
      the flanking sequences of T-DNAs in transgenic rice plants, in which the
      resistance gene for rice bacterial blight disease, Xa21, had been integrated
      stably. Sequence analysis of 24 fragments amplified by TAIL-PCR showed that of
      them 14 were rice genomic DNA, 9 contained vector backbone sequences, and one was
      a fragment of the exogenous gene Xa21. The characteristics of the 14 rice genomic
      DNA sequences at T-DNA integrated sites are significantly different from those of
      the reported rice genomic sequences into which exogenous genes were integrated
      through direct DNA transformation methods. T-DNA border sequences integrated in
      rice genome have similar features as those integrated in dicotyledonous genomes.
      In the backbone containing flanking sequences (37.5%, 9/24) vector backbones
      appeared in different types.

PMID- 11329877
TI  - [Improvement of transformation frequency of rice mediated by Agrobacterium].
AB  - The factors influencing the frequency of rice transformation mediated by
      Agrobacterium have been investigated by using 16 commercially important indica
      and japonica rice cultivars or lines. The main results were as following: For
      most rice CC medium was the best for both callus initiation and subculture. With
      supplement of 2.5-5 mg/L ABA the quality of calli can be improved. The
      concentration of selective agent for Indica rice callus was lower than that for
      japonica rice callus. Agrobacterium tumefaciens strain EHA105 was more efficient
      than LBA4404 and AGL1 for rice transformation. The inhibitive effect of
      cefotaxime to Agrobacterium was better than that of carbenicillin. The partial
      desiccation treatment after co-cultivation was beneficial to inhibit the growth
      of Agrobacterium and increase transformation efficiency. A stable and efficient
      Agrobacterium-mediated transformation system has been established in ten
      different rice cultivars and fertile transgenic plants have been obtained.

PMID- 11329878
TI  - [Phylogenetic analysis of interspecies in genus Glycine through SSR markers].
AB  - The genetic diversity among 11 species of genus Glycine (altogether 37
      accessions) was evaluated through SSR analysis. The number of alleles in
      different loci ranges from 6 to 29, averaging 15.9 per locus; alleles of subgenus
      soja account for 71.5% of those in subgenus Glycine, and the fingerprinting among
      subgenus Glycine is more divergent than that of subgenus soja. Principal factor
      analysis shows that the first and the second principal factor can classify genus
      Glycine into two groups which represent subgenus Glycine and subgenus soja. The
      results of UPGMA indicate that G. mas, G. soja and G. gracilis in subgenus soja
      are different species.

PMID- 11329879
TI  - [The distribution and homology of mitochondrial plasmid-like DNAs in different
      cucumber varieties].
AB  - Four kinds of mitochondrial plasmid-like DNA, designated pC1, pC2, pC3 and pC4,
      have been found in cucumber (Jinyan No. 4). Their distribution in 14 Cucumber
      varieties was analyzed. Plasmid-like DNAs were detected in Jinchun No. 2, Jinchun
      No. 5, Jinxinmici, Jinlu No. 4 and Jinyan No. 4, and the rest 9 varieties
      contained no plasmid-like DNAs, suggesting that their distribution is irregular.
      There was homology among the same plasmid-like DNA family in different varieties.
      pC4 showed homology to the nuclear DNA of Jinyan No. 4, in addition to the
      nuclear genomes of other 7 varieties either with plasmid-like DNAs or without.
      The homologous sequences of pC4 in the cucumber nuclear DNA were repetitive.
      Sequences homologous to pC4 were also found in the nuclear genomes of towel gourd
      and pumpkin (other cucurbitaceous plant). Therefore, we propose that
      mitochondrial plasmid-like DNA occurred before cucumber diverged from cucurbit
      and had integrated into the nuclear DNA. The varieties without plasmid-like DNAs
      might lost them during evolution.

PMID- 11329880
TI  - [Cloning and expression of TPS1 gene in Escherichia coli].
AB  - A S. cerevisiae TPS1 gene for trehalose-6-phosphate synthase was cloned by PCR
      amplification. The 1.5 kb DNA fragment was ligated to pUC19 and transformed into
      otsA deficient and deleted of E. coli strains FF4169 and FF4050 separately. otsA
      gene is encoding trehalose-6-phasphate synthase in E. coli. Restriction
      endonucleases digestion analysis of transformants' plasmid DNA showed that there
      was a cloned 1.5 kb fragment carried on the vector. The growth curve experiment
      result showed that the both transformants could grow well as wild type. Trehalose
      was synthesized and accumulated in these transformants during high osmotic stress
      by HPLC combined with ELSD (Evaporate light scatter detector) determination. From
      the result above, we could conclude that the TPS1 gene of S. cerevisiae was able
      to restore otsA gene function in E. coli for both osmotolerance and trehalose
      accumulation during salt stress.

PMID- 11329881
TI  - [Establishment of suc2 signal sequence trap system].
AB  - The secretion of proteins depends on the signal peptide located to the N-terminal
      of the protein precursor. We established a genetic system in yeast to screen cDNA
      library for the signal peptide encoding sequences. To do it, we mutated genomic
      suc2 gene (encoding yeast invertase) of EGY48 by one-step gene disruption method,
      and got yeast cell lines without invertase expression (EGY48-delta suc). To get
      vector for library screening, we inserted suc2 gene encoding mature peptide of
      invertase downstream to yeast promoter P-ADH1, and multiple cloning sites for
      insertion of library is between suc2 and P-ADH1. EGY48-delta suc transformed with
      the vector can grow on the medium with glucose as carbon source, but not on the
      medium with raffinose. Signal peptide of suc2 and alpha chain of human
      interleukin-2 was fused in frame to suc2 gene, then the two resulting vectors
      were transformed into EGY48-delta suc, all the transformants can grow in the
      medium with either raffinose or glucose as carbon source. Hence, the system
      established here can discern cDNA encoding signal peptide from the one not
      encoding signal peptide.

PMID- 11329882
TI  - Inhibition of X-ray and doxorubicin-induced apoptosis by butyrolactone I, a CDK
      specific inhibitor, in human tumor cells.
AB  - Cell-cycle progression is coordinately regulated by cyclin-dependent kinases
      (CDKs). The inhibition of CDKs by p21Waf1/Cip1/Sdi1 prevents the apoptosis of
      cells treated with DNA-damaging agents. In this study, we found that
      butyrolactone I, a specific inhibitor of CDC2 family kinases, blocks the X-ray-
      or doxorubicin-induced apoptosis of DLD1 (p21+/+) human colorectal carcinoma
      cells in a dose-dependent manner. We also found that butyrolactone I inhibits the
      CDK2 activity and enhances cell survival after an X-ray irradiation or
      doxorubicin treatment in both DLD1 (p21-/-) and DLD1 (p21+/+) cells. These
      findings suggest that butyrolactone I prevents apoptosis by the direct inhibition
      of CDK and also, possibly, by CDK-inhibition through p53-independent p21
      induction. Our findings indicate that CDK activity is required for DNA-damaging
      agent-induced apoptosis.

PMID- 11329883
TI  - 2-hydroxyadenine in DNA is a very poor substrate of the Escherichia coli MutY
      protein.
AB  - To test the possibility that the Escherichia coli MutY or MutM protein acts as a
      2-hydroxyadenine (2-OH-Ade) glycosylase, we treated double-stranded
      oligodeoxyribonucleotides containing 2-OH-Ade with the E. coli MutY or MutM
      protein in vitro. We found that a strand with 2-OH-Ade was a very poor substrate
      of MutY, irrespective of the base in the complementary strand. Moreover, a strand
      containing adenine or guanine opposite 2-OH-Ade was also rarely cleaved by MutY.
      The cleavage of oligonucleotides with 2-OH-Ade by MutM was not observed. These
      results indicate that neither MutY nor MutM plays an important role in the
      removal of 2-OH-Ade from DNA.

PMID- 11329884
TI  - Redox reactions of sanazole (AK-2123) in aqueous solutions: a pulse radiolysis
      study.
AB  - The redox chemistry of sanazole, an efficient hypoxic cell radiosensitizer,
      generally referred to as AK-2123, was studied by pulse radiolysis with eaq-, CO2
      ., 2-propanol radicals and CH2OH radicals. AK-2123 reacts with eaq-, CO2-. and 2
      propanol radicals at almost diffusion-controlled rates, producing a nitro radical
      anion (lambda max = 290 nm) within a few microseconds. The decay kinetics of the
      radical anion was independent of the pH. The radical anion reacts with oxygen
      with a rate constant of 3.4 x 10(6) dm3 mol-1 s-1. An electron-transfer reaction
      was observed from the thymine radical anion to AK-2123. From redox equilibria
      with methyl viologen, the one-electron reduction potential of AK-2123 in aqueous
      solution, determined by pulse radiolysis, was estimated to be -0.33 +/- 0.02 V
      vs. NHE. Depletion of intracellular nonprotein thiols did not mitigate the
      radiosensitizing affect of the hypoxic radiosensitizer, AK-2123.

PMID- 11329885
TI  - A susceptibility locus for radiation lymphomagenesis on mouse chromosome 16.
AB  - BALB/cHeA (BALB/c) mice are sensitive to radiation lymphomagenesis, while STS/A
      (STS) mice are resistant. We have selected a recombinant mouse, R1, with a STS
      derived D16Mit165-D16Mit34 segment in the vicinity of the centromere of
      chromosome 16 among progeny from a (CcS-7/Dem x BALB/c)F1 x BALB/c backcross. To
      test the susceptibility to radiation lymphomagenesis, we generated a genetic
      cross by mating the male and female R1 progeny obtained by 4-6 backcrosses of R1
      to BALB/c. The mice were subjected to 4 x 1.7 Gy of X-irradiation. Of 120 mice
      analyzed, 94 developed lymphomas (91, of thymic type; 3, of nonthymic type)
      within 315 days of observation. The analysis indicated a link between the
      susceptibility to lymphomagenesis and the marker D16Mit34 on chromosome 16. The
      mice heterozygous for the BALB/c and STS alleles at D16Mit34 were less sensitive
      to lymphomagenesis than the mice homozygous at this locus. There was no
      significant difference in latency among the genotypes. Our study showed the
      existence of a susceptibility locus for radiation lymphomagenesis on chromosome
      16 and revealed aspects of the genetics of lymphoma susceptibility.

PMID- 11329886
TI  - [Treatment of chronic osteomyelitis of the tarsal bones with free muscle flaps].
AB  - Although the value of free muscle flaps in the treatment of chronic osteomyelitis
      of the lower leg is well documented, only few reports deal with the use of free
      muscle flaps for treatment of osteomyelitis of the tarsal bones. Four patients
      with chronic osteomyelitis of the tarsal bones (in three patients several bones
      were involved) were treated using the following regimen: radical debridement,
      coverage with a free muscle flap, and systemic antibiotic therapy. In two
      patients, infection recurred following primary transplantation of the muscle
      flap. In one of these patients, recurrence was controlled by repeating the same
      regimen. In the other patient, debridement was repeated and the calcaneus was
      transposed to obliterate the resultant bone cavity. At follow-up (mean 19 months
      following last surgical procedure), all four patients showed no evidence of
      infection and were fully weight-bearing. Chronic osteomyelitis of tarsal bones
      can be successfully treated by radical debridement and coverage with muscle
      flaps, even in advanced stages of the disease. The clinical and anatomical
      peculiarities of this region, however, have to be taken into consideration.

PMID- 11329887
TI  - [Distal pedicled sural island flap-plasty for defect coverage of the distal lower
      extremity].
AB  - Soft tissue defects on the distal lower extremity often need extended
      reconstructive procedures, especially if tendinous, articular, or bony structures
      are exposed. The use of local flaps in the perimalleolar, pretibial and calcaneal
      area is limited, often free tissue transfer is required. The distally based sural
      island flap is a pedicled soft-tissue flap on the vascular axis of the sural
      nerve. It can be raised as a fasciocutaneous or a lipofascial flap. We report our
      experience of 16 cases, nine of these cases in the lipofascial technique. The aim
      of soft tissue coverage was reached in 15 cases. In one patient a partial
      necrosis of the flap occurred requiring a reoperation with free flap coverage.
      The main advantages of the technique are the extended arc of rotation in the
      problematic area of the ankle and the lower extremity, the easy and fast
      preparation and the stable flap perfusion. The lipofascial as well as the
      fasciocutaneous flap have some risk of loss or donor-site morbidity that can be
      avoided by adhering strictly to certain operative principles.

PMID- 11329888
TI  - [Mallet-thumb--presentation and discussion of 3 cases of a rare lesion].
AB  - Three cases of closed extensor tendon ruptures without osseous involvement in
      Verdan's zone 1 of the thumb (Mallet thumb) are presented and the various
      treatment options discussed based on the pertinent literature. As a consequence
      of the special anatomy of the thumb's extensor tendons which differs from that in
      the fingers, we recommend surgical treatment of this rare lesion by transosseous
      refixation of the ruptured tendon. Thus, early postoperative motion can be
      initiated resulting in rapid recovery of complete function.

PMID- 11329889
TI  - [Modified collateral ligament reconstruction with the tendon of the abductor
      pollicis tendon in treatment of chronic radial instability of the basal thumb
      joint].
AB  - Injuries to the radial collateral ligament of the MP joint of the thumb occur
      much less frequently than injuries to the ulnar collateral ligament. Ligament
      injury is usually a result of direct trauma. The resultant instability to the
      thumb usually impairs hand function. In acute lesions to the radial collateral
      ligament, direct repair is often possible. In cases of chronic radial joint
      instability, secondary ligament reconstruction with a free tendon graft, most
      commonly the palmaris longus tendon, is usually recommended. We describe another
      technique using the tendon insertion of the abductor pollicis brevis muscle. The
      tendon inserting distally can be used as a stable ligament after dividing it at
      the border to the muscle and attaching it to the head of the metacarpal bone with
      a wire. The follow-up for six patients treated by this method showed good and
      painless stability and function of the thumb in a time span of one year.

PMID- 11329890
TI  - [Value of several examination systems in patients with carpal tunnel syndrome.
      Comparison of Dellon computer-assisted sensation test with Mellesi hand status
      and Levine examination scheme].
AB  - The goal of the presented carpal tunnel syndrome (CTS) follow-up study was to
      compare the clinical value of the Millesi hand function score with the "Pressure
      Specifying Sensory Device" (PSSD) introduced by A. L. Dellon using self
      administered patient questionnaires. 25 patients (10 male, 15 female) with an
      electrodiagnostically confirmed CTS were enrolled in this study, performing one
      preoperative and five postoperative examinations over 24 weeks. 12 of the 25
      patients underwent an "open" two-portal carpal tunnel release with two minimal
      incisions (group OT); the other 13 patients were treated with a two-portal
      endoscopic carpal tunnel release (group ET). Additionally, in eleven out of the
      twelve patients of group OT, an epineuriotomy of the median nerve was performed
      during the same session. Concerning preoperative data of the Millesi score and
      the PSSD, no statistically significant differences were found between group OT
      and ET. However, preoperative comparison with the contralateral hand demonstrated
      a reduction in hand function of 15% and an increase in the pressure perception
      threshold of 41% compared to normative data could be measured with the PSSD. The
      subjective functional value of the hand was objectively evacuated using the
      Levine score. In the second postoperative week, a significant decrease in hand
      function could be obtained with the Millesi score in group OT. In group ET, the
      decrease in hand function representing the operative trauma was significantly
      lower than in group OT. Data of the static one- and two-point pressure perception
      threshold revealed a statistically significant improvement of the sensibility in
      both groups. The results of the Millesi score recorded at the last examination in
      the 24th postoperative week showed an improvement in hand function in both groups
      compared to preoperative data. Concerning static one- and two-point measurements
      with the PSSD, distinct improvements compared to the preoperative data could also
      be detected in both groups although significant differences between group OT and
      ET were evident: Data of group OT regarding the whole postoperative course
      demonstrate a continuous improvement in sensibility of the index finger. In
      contrast, the analysis of the PSSD measurements in group ET revealed an increase
      in all the parameters starting in the sixth postoperative week and ending with
      significantly worse static one- and two-point threshold measurements than in
      group OT. On the other hand, data of self-administered patient questionnaires
      using the Levine Score revealed significant improvements in hand function and
      reduction in pain intensity in both groups compared to preoperative results.
      Differences between both groups at the end of the examination course were not
      evident. In conclusion, the Millesi hand score with its emphasis on the motor
      function proved to be a reliable method to record the severity of CTS
      preoperatively, the severity of the surgical trauma and changes in the course of
      rehabilitation of the affected hand. A good correlation was found between data
      obtained with the Millesi Score and the self-administered patient questionnaires
      according to Levine. But when compared with the PSSD, both methods could not
      directly document the preoperative status and postoperative changes of the median
      nerve. Preoperative static two-point pressure threshold measurements with the
      PSSD confirmed their status as a screening parameter as published by A. L.
      Dellon. In the postoperative course of group ET, a distinct worsening in the
      sensibility of the index and little finger could only be detected with the PSSD
      before the patients noticed the onset of related symptoms.

PMID- 11329891
TI  - [Value of EEG monitoring in intensive care patients in plastic surgery-
      indications and experiences].
AB  - EEG monitoring can be performed at the patients' bedside and it is a valuable
      support in therapeutic decision making providing unique information about the
      functional state of the brain. Due to newer technical developments, EEG
      monitoring can be conducted rather easily. In this article, indications for EEG
      monitoring in plastic surgical patients are presented: controlling the level of
      sedation, use in states of increased intracranial pressure, screening the
      cerebral state in comatose patients, diagnosis and therapy of epileptic seizures,
      and the search for circumscribed cerebral abnormalities. Furthermore, practical
      experience with the use of the new EEG monitor Narcotrend, which is provided with
      an automatic EEG classification, is described.

PMID- 11329892
TI  - [Reconstruction of the breast areola complex. Comparison of different
      techniques].
AB  - Different methods have been used in our department for nipple-areola
      reconstruction. This study was undertaken in order to find out which method of
      reconstruction shows optimal long-term results. Between 1983 and 1999, breast
      reconstruction was performed in 204 patients and different methods were used for
      nipple-areola reconstruction. 91 patients could be examined. For areola
      reconstruction full-thickness skin grafts from the groin were used as well as
      skin grafts from the contralateral areola, vaginal mucosal grafts, and tattoos.
      For nipple reconstruction we used nipple sharing, labium grafts, local flaps, and
      a tattoo. Areola reconstruction with full-thickness skin grafts from the groin
      was performed in 45 patients, in 16 patients a graft from the contralateral
      areola was used and in 19 patients the technique of intradermal tattoo was
      applied. One patient had a vaginal mucosal graft, in another patient the nipple
      areola complex was transplanted to the groin after mastectomy for later
      reconstruction. Nipple projection was measured and the colour of the
      reconstructed areola was compared to the other side. Concerning the match of
      colour, best results were achieved with grafting from the contralateral areola,
      followed by areola tattoo and skin grafts from the groin. The vaginal mucosal
      graft was too dark. The transplanted original nipple-areola complex maintained
      its colour. Nipple projection between 3 and 4 mm was achieved by nipple sharing
      and local flaps. With grafts from the labium, a projection from 1 to 2 mm was
      achieved. Thus, best results were achieved by nipple sharing, local flaps for
      nipple reconstruction and areola skin grafts from the contralateral side. Vaginal
      mucosal grafts and grafts from the labium are not recommended.

PMID- 11329893
TI  - [Presentation of plastic surgery on the internet: experiences with the home page
      of a department].
AB  - Plastic surgeons are increasingly taking advantage of information opportunities
      offered by the internet. Between October 1998 and March 1999, 87 individuals
      returned by e-mail a feed-back form included in the homepage of the Division of
      Plastic Surgery, Department of Surgery, Karl-Franzens University School of
      Medicine, Graz, Austria. Most of the responses originated from Austria or other
      European countries; 10% were from overseas. The most frequent reason for visiting
      our homepage was to gain information on scientific activities in our department
      (43 visitors), followed by interest in plastic surgical procedures on the part of
      patients or referring physicians (35 visitors). Other reasons were interest in
      educational matters, positions, and general interest in plastic surgery. Our
      results show that physicians, medical students, and laypersons are increasingly
      inclined to seek information on plastic surgery via the internet. This in turn
      should encourage plastic surgery services to present themselves in the World Wide
      Web.

PMID- 11329894
TI  - [Anatomy of the dorsal mid-hand arteries--anatomic study and review of the
      literature].
AB  - By dissections of 20 cold-preserved hands, we investigated the dorsal metacarpal
      arteries (DMA) with regard to reliability, origin and anastomoses. The first
      dorsal metacarpal artery showed a trifurcation with three vessels: Ramus ulnaris
      (A. metacarpalis dorsalis I), Ramus medialis and Ramus radialis (A. ulnodorsalis
      pollicis). The DMA II to IV were observed medially in their respective
      intermetacarpal spaces. The A. metacarpalis dorsalis V was unreliable in reaching
      the skin of dorsal proximal phalanges as in the DMA IV. Most reliable for
      reaching the skin of dorsal proximal phalanges were the radial arteries--first,
      second and third dorsal metacarpal arteries. The dorsal digital arteries
      originate close to one another at the level of the metacarpophalangeal joints.
      There was an increase of epifascial position, from radial to ulnar. Irregular
      palmar intermetacarpal anastomoses were found proximal to the ligamentum
      metacarpale transversum profundum but nearly consistently in the web space.

PMID- 11329895
TI  - [Covering defects of the basal finger area by pedicled flaps anastomosed to the
      doral metacarpal arteries].
AB  - Between 1993 and 1998, 12 distally based dorsal metacarpal artery flaps were used
      to cover defects of the fingers and palm. All flaps were raised from the dorsum
      of the hand. Eleven flaps allowed direct closure of the donor site area; one case
      required a full-thickness skin graft. Nine flaps healed uneventfully. Distal
      marginal flap necrosis occurred in three cases. All of these were used to cover
      defects at the distal part of the middle phalanx.

PMID- 11329896
TI  - [Revascularization and defect coverage of the hand: special applications of the
      radialis forearm flap].
AB  - During the last years, a large number of newly designed flaps have been
      presented, suitable to cover defects of the hand. Some of them, namely the
      retrograde interossea-posterior and the lateral arm flaps, found their way into
      daily clinical routine. They even seem to have replaced the standard flaps for
      defect coverage to the hand, the pedicled groin flap and the radial forearm flap.
      Especially the radial forearm flap seems to become an obsolete procedure, as it
      requires sacrificing a main forearm artery. Three patients are presented who
      suffered from complex injuries to their hands and were treated with radial
      forearm flaps in a single-stage primary procedure. In two hands, the arterial
      palmar arches and the soft-tissues of the palm were reconstructed by use of a
      distally pedicled radial forearm flap. Collateral arteries of ischemic fingers
      were implanted into the flap artery to achieve revascularization and a vein graft
      was interposed between the stumps of the radial artery to reestablish an
      orthograde blood flow. A free radial forearm flap harvested from the
      contralateral uninjured forearm was used to replant a torn-out forearm. In all
      cases, primary healing was achieved without complications. Primary treatment of
      complex injuries to the hand and forearm often requires revascularization of
      ischemic parts of the limb and coverage of large soft-tissue defects at the same
      time. The radial forearm flap, either as a distally pedicled flap or as a free
      flap, meets all the needs or in particular is appropriate to perform such
      demanding primary procedures. The destruction of the arterial palmar arches does
      not present a contraindication against the use of a distally pedicled radial
      forearm flap, but actually is a strong indication to reconstruct the radial
      artery by a vein graft.

PMID- 11329897
TI  - [Treatment of 3rd degree fingertip frostbite in a mountain climber with semi
      occlusive dressings].
AB  - Deep frostbites of the fingertips mostly result in some form of amputation. To
      preserve functional length and to achieve good sensibility, we managed deep
      frostbites of five fingertips of a mountain climber with semiocclusive dressings.
      The method was described by Mennen and Wiese (1993) for the management of
      fingertip injuries. To our knowledge, the method has not been used so far in the
      treatment of frostbites. The two fingertips presenting only deep soft-tissue
      damage achieved a nearly normal recovery of pulp shape and sensibility. The three
      fingers with bone involvement required a long period of time for complete
      healing. In two of these fingers, additional bone shortening had to be performed.

PMID- 11329898
TI  - [The chances for social medicine].

PMID- 11329899
TI  - [Social medicine for the future].

PMID- 11329900
TI  - [Social medicine from the political viewpoint].

PMID- 11329901
TI  - [Needs and need adjusted service from the viewpoint of expert consultants].

PMID- 11329902
TI  - [Awarding the Salomon-Neumann Medal].

PMID- 11329903
TI  - [Health promotion and international health policy].

PMID- 11329904
TI  - [Necessary and desirable future emphasis in social medicine from the theoretical
      viewpoint].
AB  - Social medicine, like medicine as a whole, is based on biomedical science and has
      responsibilities in clinical care, at the same time linking the health system, an
      important element in the welfare state, to society. Social medicine investigates
      and expands the scientific basis for securing and promoting health by way of
      social action, sharing common roots with public health. In the biomedical sphere,
      emphasis is on improving our understanding of the biological foundations of
      social behaviour; scanning and assessing the ethical, legal, economical and
      social implications of scientific progress; influencing the social and economic
      effects of demographic developments, and improving the scientific basis of
      preventive, styles of living and interventions. In the clinical sphere, the main
      objectives are to expand such areas as clinical epidemiology and clinical health
      economics, to assert patients' rights and to promote population-related medicine
      in the training of doctors. As far as the health care system is concerned,
      emphasis is on restoring the solidarity concept between the healthy and the sick
      as the principle of statutory health insurance, and on securing transparency of
      performance, quality, and cost. A further objective is to encourage more creative
      management by the health insurance funds by granting freedom of contract. Open
      public discussion about the rationale of an ethical health care system is
      required, discussion in which independent experts trained in population-related
      medicine must play an active part.

PMID- 11329905
TI  - [Reality and social interpretation of health].
AB  - The health profile of a human society depends upon its social development and in
      particular upon current social and cultural conditions. Health can be defined in
      many ways; both the pathogenetic and the salutogenetic approaches have their
      merits. Partial aspects of reality are offered for example by attempts to
      describe health conditions quantitatively by means of health indicators such als
      life expectancy, mortality, morbidity, incapacity to work, use made of medical
      services, and the like. The description of health must encompass the entire range
      of its objective and subjective experience in its somatic, mental and social
      dimensions. Epidemiological data must always be supplemented by the results of
      phenomenological observations to obtain a true picture of the experience of
      reality and the acceptance of the results by the group under observation.

PMID- 11329906
TI  - [The future of social medicine from the practical viewpoint].
AB  - Within the German statutory health care system the practice of sociomedicine as
      an applied health science is mainly related to individual aspects of theinsured
      persons. Combining factors due to medical and socio-economical developments it
      plays an important integrative role as so to say a lawyer of the patients.
      Furthermore, practical sociomedicine must provide consultant services to support
      the social insurance in the sphere of shaping the health care system. Profound
      knowledge on the required level must be acquired by graduate studies and can be
      deepened by well-planned continuing medical education. Professionalism in
      providing services and fulfillment of legal obligations can be achieved by
      standardisation of social medical procedures, scientific orientation towards
      public health aspects, appropriate methods of delivering medical knowledge, use
      of information systems, refinement of co-operation, quality management, social
      medical controlling, application of modern planning and control concepts as well
      as model leadership.

PMID- 11329907
TI  - [In the chosen occupation health must also play a part! An analysis of
      occupational medicine assessment of adolescents with health handicaps].
AB  - When choosing a profession or occupation, the interests, the abilities, the
      inclination, innate propensities and, last but not least, health must be
      considered. Being fit for the job prevents dropouts in vocational education and
      from giving up the occupation, and avoids cases of employment rehabilitation.
      Before the decision on a vocational training is taken, a medical examination and
      consultation of an occupational and sociomedical expert should be mandatory. The
      results of a study on the reasons of the vocational education dropouts or for
      giving up the occupation are presented and conclusions for improvement are
      discussed.

PMID- 11329908
TI  - [Interreg II--European regional study of chronic respiratory tract diseases in
      children in the Germany-Netherlands border zone].
AB  - AIM OF THE STUDY: In Westelijke Mijnstreek (WM), Midden-Limburg (ML), both The
      Netherlands, and Kreis Heinsberg (HS), Germany, the relationship between quality
      of the indoor environment and respiratory symptoms in children was studied,
      finally resulting in proposals for prevention of respiratory symptoms in the
      three regions. This paper presents the results of the first part of the study,
      investigating prevalences of respiratory complaints. METHODS AND RESULTS: A brief
      questionnaire was used to document prevalences of respiratory complaints,
      physicians diagnoses and treatment in about 7,000 children 5-6 resp. 7-8 years of
      age from HS, ML and WM, in 1995 and 1997. Prevalences of respiratory symptoms
      differed slightly between the regions, but there were differences in physician
      diagnosed asthma and bronchitis and treatment of the children. PERSPECTIVES: The
      brief questionnaire is a useful instrument to get an overview on respiratory
      symptoms. Since 1995, it is used by several German Municipal Health Services for
      Public Health Reports.

PMID- 11329909
TI  - [Surveillance of drinking water supply with a geographic information system: a
      pilot project of the of the Iogd NRM and the Hoxter district].
AB  - Drinking water surveillance includes the use of spatial data. A geographic
      information system (GIS) is a practicable tool for work with spatial data in the
      health sector as well. Co-operation between the Institute of Public Health for
      North Rhine Westphalia, the local health authority of the Hoexter district and
      the Institute for Geoinformatics of the University of Muenster started a project
      testing the use of GIS for drinking water surveillance. A special application was
      programmed. It includes functions of retrieval and classification of the measured
      values of drinking water wells, in order to show time trends in a diagram and to
      visualise the location of the wells and the analysis data in a map. The members
      of the Public Health Office accepted the method and started using it regularly.
      In addition, the collaboration between the health authority and other local
      authorities was strengthened. Several data sets were included in the GIS, such as
      wells and results of water analysis, water protection areas, land use data, and
      topographical maps. Basing on to the experiences with this project, the
      development of a standard application is planned that is supposed to be
      communicated to all local health authorities in North Rhine Westphalia.

PMID- 11329910
TI  - [Effect of a back education program by the Lower Saxony AOK in response to the
      development of health related quality of life and occupational disability].
AB  - The statutory sickness fund AOK Lower Saxony developed a specific course  program
      for a target group of    up to 55-year old employees with common back pain in the
      early  satge of chronification. Comparative evaluation of effects in study
      participants and controls was achieved by quality of life and performance data,
      i.e. days  of sick leave (DSL). Medium and long-term change inquality of life (6
      and 12 months after the course) was assessed by means of the SF-36 dimensions for
      cases and controls and compared in bivariate and multivariate test. 92 of 197
      baseline participants (or 127 participants who completed the programme) and 483
      controls were included in the medium term effect analysis. Significant medium and
      long-term net efffects could only be shown for pain  dimensions. Anonymised DSL
      data for all 5409 insured persons who were initially selected as potiential
      participants for the regionally restricted course programme in the second quarter
      of 1997 were available for the period from 01-01-1996 to  30-06-1999. For
      controlling any selection bias and potential regional differences, the initial
      DSL trends of the 197 baseline course participants were compared with two control
      groups, namely other insured from the programme region and control regions. DSL
      trends in the three groups prior to the course program were identical.
      Subsequently DSL due to ICD-9 Codes 710-739 were reduced more substantially in
      course participants than in controls: 25.5 versus 33 or 32 days respectively. A
      covariance analysis model that also considered socio-economic factors and pre
      intervention DSL levels yeilded a 14-day reduction in DSL (p value 0.023). This
      is a clear effect on DSL trends taht may be utilised for net savings for AOK. 
      This is also the first proof of a backpain programme outside company settings
      taht permits net savings.

PMID- 11329911
TI  - [Data protection--an obstacle for prospective studies? Solutions exemplified by a
      cohort study].
AB  - Prospective studies require the storage of the participants' personal data for
      follow-up. This demands special precautions for the protection of these data.
      Additional to the informed consent of the participant which enables the
      researchers to collect the prospective study data, the participant's right of
      informal self-determination should be protected. In the EPIC (European
      Prospective Investigation into Cancer and Nutrition) Potsdam study, therefore, an
      internal trustee was established that collects follow-up information from
      participants, physicians, clinics, health offices, tumour and population
      registries with the aim to obtain valid information on vital status and diseases
      of the participants. The internal trustee is a spatial and organizational
      separated working group. The isolated electronic data processing network, the
      alarm system which controls the rooms of the working group, the access control
      for employees are special security arrangements. During follow-up the individual
      identification number of the study data base is replaced by a specific
      identification number solely for the follow-up. Further, unique identification
      numbers are allocated to every single action and every single document such as
      inquiry forms which are sent to physicians, health offices, or population
      registries, that allow anonymous mailing and processing of the collected
      information. On copies of important documents, the name is erased and replaced by
      a specific record number. The inquiry forms for the physicians, for instance,
      contain the name of the participant at the head which has to be cut off before
      returning the form to the internal trustee. The identification number is also
      printed as bar code on each document facilitating its processing with technical
      aids such as scanners. If checkbacks are necessary, only certain work group
      members are able to reconnect the document number with the name. Depending on the
      task, the computer programmes confine automatically the details presented to the
      assistant. All arrangements to protect personal data do not interfere with
      research interests; on the contrary they lead to an efficient work routine and
      guarantee follow-up according to international rules.

PMID- 11329912
TI  - [Reducing income inequity and boosting social capital: new responsibilities in
      social epidemiological research].
AB  - This paper focuses on the fact that there are not only large inequalities in
      health between but also within countries. The question is raised as to whether
      these two types of health inequalities are caused by similar processes, and
      whether understanding these processes could lead to new strategies for reducing
      such differences. Many studies in Germany have demonstrated that mortality and
      morbidity are much higher for low-status as compared to high-status population
      groups. These health inequalities are usually explained by differences in working
      and living conditions, in health behaviour and in health services utilisation.
      For some years there has been an extensive discussion in the international Public
      Health community on health inequalities between countries and on how they can be
      explained by income inequalities, with the term "social capital" becoming a
      central issue. This debate has been largely neglected in Germany, but such
      groundwork now offers an important opportunity for a more comprehensive
      discussion in this country as well.

PMID- 11329913
TI  - [A career in promoting social medicine].

PMID- 11329914
TI  - [Epidemiology, social medicine, environmental medicine--a plea for a difficult
      but necessary integration].
AB  - The origins of environmental medicine date back more than 2000 years. The
      increasing incidence of environmental disease together with successful research
      into their etiology and pathogenesis have caused an impetus for this discipline
      in quantitative terms. A growing interest of patients, but also of politicians
      and parts of the industry in actual or suspected environmental risk factors for
      health have given rise to controversies--rendering the development of a rational,
      quality-oriented environmental medicine difficult, if not impossible. Given these
      controversies surrounding environmental health issues formal demarcations between
      the traditional disciplines (environmental) epidemiology, social medicine,
      occupational medicine, and environmental medicine become obsolete. Instead, a
      common agenda with respect to research, quality assurance, risk communication,
      and prevention as well as patient counselling and policy advising calls for a
      conceptual and institutional integration of these disciplines.

PMID- 11329915
TI  - [European standardization and German language adaptation of scales for collection
      of outcomes and costs of treatment for patients with severe mental disorders].
AB  - For the evaluation of the effectiveness of psychiatric service systems
      internationally standardised instruments for the assessment of the outcome and
      the costs of psychiatric and psychosocial treatment and care are increasingly
      needed. Beside the measurement of objective facts there is a growing importance
      of the consideration of the subjective perspective of patients and relatives. In
      the research project "Cost-effectiveness analysis of psychiatric service systems
      in the European comparison" of the Research association for Public Health in
      Saxony, developments were worked out, in close cooperation with the BIOMED-2
      project "European Psychiatric Services: Inputs Linked to Outcome Domains and
      Needs", German versions of five European standardized instruments for the
      assessment of needs for care, treatment satisfaction, burden of care on
      relatives, quality of life and service costs. The psychometric properties of the
      instruments were tested within the framework of a longitudinal study with 307
      patients with the diagnosis of schizophrenia. As a result of this study, German
      versions of all relevant European instruments for psychiatric service evaluation
      are now available.

PMID- 11329916
TI  - [Preventing skin damage in beauticians].
AB  - The incidence of occupational dermatitis of the hands is particularly high in the
      hairdressing trade. To elucidate the role of various risk factors, and to
      ultimately improve primary prevention of occupational hand dermatitis, a
      prospective cohort study was conducted between 1992 and 1997, including 2352
      hairdressing trainees. Already six weeks after the start of training (median)
      35.4% had--usually mild--irritant skin changes, mainly involving the interdigital
      web spaces. These were associated with subsequent, possibly more severe, hand
      dermatitis. Reduced exposure to wet work, i.e., improved skin protection with
      gloves, often led to the resolution of dermatitis of the hands. In conclusion,
      early irritant skin damage is a sentinel event that heralds possibly disabling
      occupational skin disease and should prompt adequate preventive measures.

PMID- 11329917
TI  - [Challenges in social medicine counseling and expert assessment].
AB  - The services of expert testimony and professional consultation in sociomedicine
      are considerably challenged. It is not so much the question of maintaining their
      traditional functions but of developing them in order to maintain at least the
      status quo. These challenges consist for example of the lack of a scientific
      basis for the complex function of allocation, piloting and control of medical
      resources. Some new approaches are offered by the ICIDH, by new instruments of
      medical assessment and by quality management including "evidence-based medicine".
      Furthermore the services of expert testimony must bridge the gap between patients
      and social services in a way which is satisfactory for the population.
      Nevertheless, these services must maintain strict independence.

PMID- 11329918
TI  - [Ambulatory long-term cardiac rehabilitation--one year results].
AB  - After acute hospital therapy of myocardial infarction or bypass surgery the
      patient in Germany will be treated using an inpatient rehabilitation programme
      for 3-4 weeks. One year later only 10% of them are still active in outpatients
      groups. In our study 61 cardiac patients performed an one-year outpatient
      rehabilitation (instead of 4 weeks inpatient) programme with intense supervised
      exercise and behaviour therapy. The money input per patient was the same for the
      usual care 4 weeks inpatient (6000 DM) as for 1 year outpatient rehabilitation
      (5800 DM). The exercise capacity per heart rate-blood pressure-product was
      increased by 43% (p > 0.01) after 12 months. The maximum exercise capacity was
      reached in the 57th week. Without increased medical treatment, cholesterol and
      LDL-cholesterol were reduced after 12 months by 3.9% down to 195 +/- 25 mg/dl or
      by 6.6% down to 122 +/- 21 mg/dl, respectively (n.s.). HDL-cholesterol increased
      by 2.8% to 48 +/- 8 mg/dl (n.s.). This study shows results similar to outpatient
      rehabilitation programmes in the United States or in Sweden. The long
      intervention time and the intensity are main factors for the success of cardiac
      rehabilitation and patient health. Financial resources should primarily be
      concentrated on long-term outpatient rehabilitation programmes.

PMID- 11329919
TI  - [Social urban development and poverty control as health promotion].
AB  - The Salomon Neumann Medal of the German Society for Social Medicine and
      Prevention bears the inscription. "Medicine is a Social Science". This
      provocative statement is most topical. It compels us to actively promote health
      by healthier living and environmental conditions apart from medical prevention. A
      core of this sphere of action is the reduction of social inequalities. Several
      recent congresses and publications have clearly shown that this subject remains
      one of the biggest challenges facing health promotion. German law has set the
      signs for reducing socially rooted inequalities for chances of health. This
      article postulates the thesis that health promotion can find allies for a healthy
      public policy in programmes planning for healthy urban development and for
      combatting poverty. The specific approaches for combatting social inequalities in
      the health sphere are reported and examples are given how such a health promotion
      policy may be translated into reality on a communal level. Finally, spotlight is
      on the dilemma of combatting inequality of chance due to differences in social
      status.

PMID- 11329920
TI  - [Urban development and health].
AB  - Urban development and Municipal Health Promotion complement each other. Where as
      urban development is based on normative regulations and--with regard to health-
      rather orientates to protecting against health hazards, municipal Health
      Promotion aims beyond that at the mobilisation and strengthening of public and
      individual health resources. Both spheres should undergo greater integration in
      the future.

PMID- 11329921
TI  - [Health promotion, health promoting education and social inequality].
AB  - Health promotion should consider social equality more strongly in order to
      maintain its credibility. The school is an appropriate setting for such
      interventions. Social-epidemiological studies prove that the school setting has a
      great homogenising influence. Because of its education programmes it also reaches
      fringe groups. Experiences from two German pilot projects on Health Promoting
      Schools offer concepts which can be effectively used for these interventions. It
      is recommended that interventions take place on different levels (school level,
      curriculum, teacher in-service training, political level), so the HPS can
      completely unfold its influence. The chance for realisation is seen in linking
      the orientation to different life domains and basic principles of education. The
      more critical processes of changing of society and the growing pressure in
      schools are seen as risk factors for a healthy balance of the school and for the
      students as well as teachers.

PMID- 11329923
TI  - [Confidentiality within the scope of secondary data research--approaches to a
      solution of the problem of data concentration].
AB  - In order to implement general data protection requirements and internationally
      recognised ethical requirements, research with personal health and social data
      demands a specific framework for the secure handling of confidential data. In the
      process of transferring data from the health service providers to the place where
      they are analysed, an important role is played by a so-called trust centre,
      responsible for pseudonymisation of personal and institutional identifiers. An
      undesirable concentration of data in the trust centre can be avoided by early
      separation of data in the data transfer institution: the trust centre receives
      only the identifier to be pseudonymised, while the health provision data are sent
      direct to the analysing institution, where they can be matched with the
      pseudonyms from the trust centre, with the help of a unique case number. The
      possibility of reidentification, which exists mainly in large (pseudonymised)
      data sets, can be reduced by use of an appropriate pseudonymisation process (e.g.
      insuree-based pseudonymisation by health service providers for sampling of
      insurees). The measures described here are suitable for protecting
      confidentiality and for further improving data security in the handling of
      confidential personal and institutional data.

PMID- 11329922
TI  - [The health of students during their education].
AB  - Longitudinal changes of health and well-being during the course of studies at the
      university have been rarely studied in Germany so far. Therefore, data were
      analysed from a cohort of 166 students who took part in a baseline survey as
      freshmen at the beginning of their studies and in a follow-up after two years.
      The questionnaire assessed the frequency of symptoms and complaints, psycho
      social and study-related sources of stress and health attitudes and perceptions.
      Longitudinal trends were studied based on variables identified by factor
      analysis. The results showed no changes in physical health indicators (complaints
      and self-rated health status), while the mental stressors with respect to study
      demands, study conditions and private situation showed significant increases. On
      the other hand, there were moderate increases observed in health awareness and
      physical activity of students from baseline to follow-up. We conclude that the
      increase in perceived mental stress indicates a vulnerability during the initial
      study. In addition, the positive developments regarding health awareness of
      students during studies should be supported by health promotion measures at the
      university.

PMID- 11329924
TI  - [Status of the social inequality topic and health in the periodical "Das
      Gesundheitswesen"].
AB  - People with social problems and risks very often also suffer from health problems
      and risks. This refers to at least 10% of the population. We were interested to
      learn how many articles in the leading German journal of Public Health "Das
      Gesundheitswesen" are dealing with this topic of social inequality and health.
      From 1990 to 1999 just 5.4% of the 1399 published articles deal with this topic.
      The authors mainly came from social epidemiology; practical research was rare.
      This also seems to be a consequence of a lack of research in the departments of
      social work education.

PMID- 11329925
TI  - [Community health policy as a research area in public health and social
      sciences].
AB  - The community plays a central role in new public health concepts. However, local
      health policy has not achieved a central role in cities and counties. Therefore
      it seems to be both reasonable and necessary for social sciences to analyse the
      health options in local politics and to identify aspects for improvement. The
      implementation of health priorities and their realisation at the local level, the
      latter with regard to supporting (positive) and hampering (negative) factors, and
      the development of strategies to implement health programmes are suggested as
      main research topics. Starting from the assumption that complex organisational
      processes in communities need organisational support, the role of the public
      health service as coordinating and initialising factor for the alteration of
      community health programmes should be investigated more thoroughly. The public
      health service as a part of the administration in municipalities is also involved
      in the endeavour to modernize administration. A main area for research will be
      how far the knowledge about participation of citizens and new management theories
      support health as a task of local politics.

PMID- 11329926
TI  - [The Augsburg cooperation model for promoting dental health in childhood].
AB  - Dental care in children and adolescents has been remarkably successful in the
      recent past. For the purpose of reducing dental caries risk still further, a
      cooperation model has been developed which combines the elements of diagnosis,
      group prophylaxis, individual intensive prophylaxis and if necessary dental
      treatment. This involves cooperation between the Bavarian Provincial Working
      Group for Dental Health, statutory sickness insurance, practising dental surgeons
      and Public Health Services.

PMID- 11329927
TI  - Migration and health.

PMID- 11329928
TI  - [Current research perspectives of health system research and health economics in
      Germany].
AB  - The German statutory health insurance scheme is confronted with a steadily rapid
      progress of medical sciences and increasing difficulties to mobilize the
      financial resources necessary for applying the new scientific knowledge in health
      care. Therefore it is absolutely imperative to intensify the efforts to improve
      the effectiveness and efficiency of health care. Health policies based on health
      targets, the development of patterns requiring integrated care, redefining the
      bunch of health insurance benefits, and a more regular use of methods of economic
      evaluation have been proposed as promising approaches towards optimizing resource
      allocation in health care. However, an analysis of these approaches demonstrates
      that a valid appraisal of their potential to improve the effectiveness and
      efficiency of health care requires further research. In addition, European
      integration may produce tendencies towards a convergence of the national health
      care systems; this makes it rather difficult to assess how the room for
      autonomous national health policies will develop in the future.

PMID- 11329929
TI  - [Rapid assessments"--quick evaluation of medical technology].
AB  - Assessing the clinical, economical and other consequences of medical technologies
      (health technology assessment, HTA) is an important instrument to support
      decisions in many health care systems. A comprehensive HTA, however, is time
      consuming and costly while, on the other hand, decisions have to be made quickly.
      A number of international HTA programmes established rapid assessment tracks
      although they are variable in scope and methods. In the first part of this paper,
      these programmes were compared with respect to scope, methods and time to
      complete assessments. It can be shown from this comparison that there is no
      common definition of "rapid assessments". In the second part of the paper, a
      model for processing rapid assessment in the German context is introduced and
      discussed. The model aims at rapid assessments serving the needs of German
      decision-makers and ensuring high scientific quality at the same time. The model
      consists of a modular system that is tailored to the actual demand of the
      decision-maker. Modules are obligatory (such as a systematic literature search)
      or optional (such as meta-analysis). All modules are subject to standardisation
      as far as possible. However, it should be kept in mind that a close collaboration
      between commissioners and executives of an HTA is necessary to focus on the
      question and work out the HTA accordingly.

PMID- 11329930
TI  - [Illness concepts and illness experience of patients and their family physicians
      in varicose ulcer].
AB  - Venous ulcers are common in ambulatory care, but there is not much known about
      the epidemiology or diagnostics and therapeutic strategies in the care for
      patients by German general practitioners (GPs). In a broader research context we
      study patients' and their GPs' concepts of disease and their influence on health
      outcomes. In a pilot study in 1999 a representative sample of all GPs in the
      State of Hesse (n = 319) are sent a questionnaire. Open problem-centred oral
      interviews are effected with an asystematic sample of 3 GPs and 2 ulcer patients
      (n = 6) of each GP to generate hypotheses. In the main study a representative
      sample of all GPs in the State of North-Rhine are included. They name all of
      their patients with a fresh venous ulcer during the following 18 months.
      Especially patients' pain is underestimated by the GPs. From their point of view
      difficulties in the therapeutic process are often due to 'non-compliant'
      behaviour of patients. Patients' perceptions of illness and their handling differ
      individually and are only partially known to the GPs. Concepts of disease and
      ideas of what is to blame for the development of disease vary considerably.

PMID- 11329931
TI  - [Women and sex-specific health research in the German Society for Social Medicine
      and Prevention].
AB  - Since the 1970s women's health research has put gender-specific topics on the
      agenda of health research and practice. Based on a social science approach, it
      focuses on social conditions of the maintenance of women's health and of their
      needs in prevention, health promotion, medical treatment, and rehabilitation.
      Besides an analysis of woman-specific topics (such as sexual violence or drug
      abuse) women's health research addresses questions of gender bias in health
      research. In Germany, guidelines are lacking that ensure appropriate attention to
      gender issues for health research. The section "Woman-specific and gender
      specific health research" of the German Society for Social Medicine and
      Prevention (DGSMP) intends to intensify the discussion on the gaps in health
      research and prevention and on the development of guidelines to detect gender
      bias. The main goal is to implement the concept of gender mainstreaming in public
      health.

PMID- 11329932
TI  - Endothelial progenitor cells for regeneration.
AB  - Endothelial progenitor cells (EPCs) have been recently isolated from peripheral
      blood and bone marrow (BM), and shown to be incorporated into sites of
      physiological and pathological neovascularization in vivo. In contrast to
      differentiated endothelial cells (ECs), transplantation of EPCs successfully
      enhanced vascular development by in situ differentiation and proliferation within
      ischemic organs. Based on such a novel concept of closed up function on EPCs in
      postnatal neovascularization, the beneficial property of EPC is attractive for
      cell therapy as well as cell-mediated gene therapy applications targeting
      regeneration of ischemic tissue.

PMID- 11329933
TI  - Epithelial cell differentiation during stomach development.
AB  - Chicken stomach provides an extremely useful experimental system for the analysis
      of molecular nature of the morphogenesis and cytodifferentiation of digestive
      organs in vertebrates. We identified several genes of which expression is
      important for the normal development of the stomach. Especially, bone
      morphogenetic protein-2 is necessary for the mesenchymal action in inducing gland
      formation in the epithelium of the stomach. Some transcription factors such as
      cSox2 and cGATA5 are involved in the expression of embryonic chicken pepsinogen
      gene, a marker gene of stomach gland epithelial cells.

PMID- 11329934
TI  - Effects of embryotrophic factors on the embryogenesis and organogenesis of mouse
      embryos in vitro.
AB  - In order to study embryogenesis and organogenesis in vitro, two cell mouse
      embryos were cultured with alpha-MEM supplemented 10% FCS and embryotrophic
      factors (ETFs). The ETFs were separated from the conditioned medium of a SKG-II
      SF cell line derived from a human uterine cervical epidermoid carcinoma. IL-1
      beta, IL-6, IL-8, EGF, GH, PDGF-AB, basic FGF, VEGF were also detected in the
      conditioned media of this cell line. Using ETFs and a 10% FCS supplemented
      culture medium, 23% of the mouse two cell stage embryos developed to the
      bilaminar disc stage, 13% to the trilaminar germ disc stage, 9% were observed
      with blood islets in the yolk sac, and the heart beat was noted in 7% (28
      embryos) of the embryos. Furthermore, primordial organs, such as the liver,
      heart, kidney, notochord, retina-like structure, etc. were observed. Usually,
      structures associated with the primordial streak stage (bilaminar germ disc
      embryo) developed in vitro using ETFs from two cell stage embryos. These closely
      resemble structures found at the same stage in the normal embryo in vivo. After
      the primordial streak stage, the cultured embryos showed no resemblance to the
      same stage in normal embryos. None of the external appearances of these embryos
      appeared normal. On the other hand, trilaminar disc stage embryos never developed
      when using only a 10% FCS supplemented culture system.

PMID- 11329935
TI  - Mouse fetuses by nuclear transfer from embryonic stem cells.
AB  - At present, two methods for cloning mammals by nuclear transfer are employed. The
      first is based on cell fusion and has been applied to domestic animals, such as
      sheep, cows, and goats. While, nuclear microinjection has been used in mice only.
      Cloning by nuclear transfer has been reported mainly with cells from primary
      culture and freshly isolated cells. Here, using ES cell line TT2, we tried to
      produce clone mouse embryos by the two methods. With ES cell line TT2 (10-13
      passaged), 16% of reconstructed oocytes microinjected with the nuclei developed
      in vitro to the morula/blastocycst stage, and 50% of these embryos developed to
      fetuses until 14 dpc when transferred to pseudopregnant females. At 20 dpc
      implanted sites were degenerated and absorbed. Also, in vitro development of
      embryos reconstructed by electrofusion shown similar results. But, when
      transferred to recipients, subsequent development of embryos showed lower rates,
      as compared with embryos microinjected and from recipients live-born pups could
      not be obtained.

PMID- 11329936
TI  - Sensitivity of human pancreatic adenocarcinoma tumor lines to chemotherapy,
      radiotherapy, and hyperthermia.
AB  - BACKGROUND: Surgical treatment of pancreatic adenocarcinoma has failed to produce
      many cures secondary to high rates of intraperitoneal relapses and liver
      metastases. The aim of this ex vivo study was to evaluate the inherent
      chemosensitivity, radiosensitivity and hyperthermic sensitivity of pancreatic
      adenocarcinoma and to investigate the usefulness of a 3-(4,5-dimetylthiazol-2-yl)
      2,5-diphenyl tetrazolium bromide (MTT) assay utilized in each sensitivity test.
      METHODS: Nine human pancreatic adenocarcinomas were tested ex vivo after growth
      in nude mice. After 72 hr of chemotherapy, radiotherapy and hyperthermia,
      efficacy was assessed using MTT assay to determine the ratio of surviving
      fraction of treated cells-to-that of untreated control cells (TIC ratio).
      RESULTS: Tumor sensitivities as measured by the IC50 (drug concentration
      producing 50% growth inhibition) varied largely between drugs, ranging larger
      than 3 x 10(5) ng/mL for 5-FU, larger than 1.5 x 10(2) ng/mL for MMC, 20 ng/mL to
      1.4 x 10(3) ng/mL for ADM, and 80 ng/mL to 2.4 x 10(3) ng/mL for CDDP. D0 (dose
      of radiation reducing the surviving fraction to 37%) ranged from 3.2 to 8.3 Gy
      (mean +/- standard deviation; 5.8 +/- 1.6 Gy). For hyperthermia, the mean T50
      (duration of hyperthermia reducing the surviving fraction to 50%) at 43 degrees C
      was 9.4 +/- 3.3 min 4.8 to 14.2 min). The T/C ratio at 43 degrees C for 12 min
      was less than that at 41 degrees C for 30 min (p = .01; the Wilcoxon signed-ranks
      test). No clear relationship among chemosensitivity, radiosensitivity,
      hyperthermic sensitivity and pathologic features could be established.
      CONCLUSIONS: Nine human pancreatic adenocarcinomas varied widely in their
      sensitivity to chemotherapies, especially for 5-FU. These results suggested that
      MTT assay may be useful in excluding some less sensitive cases of pancreatic
      cancer. For hyperthermia, sufficient therapeutic time and temperature may realize
      enough effect against pancreatic adenocarcinoma.

PMID- 11329937
TI  - N-acetyl cysteine inhibits cell cycle progression in pancreatic carcinoma cells.
AB  - The antioxidant N-acetyl cysteine (NAC) is a precursor of intracellular
      glutathione (GSH) and is also a well known as one of the chemopreventive agents
      which act through a variety of cellular mechanisms. We examined the effects of
      NAC on cell cycle progression in the pancreatic carcinoma cell lines, SW1990 and
      JHP1. Cells were incubated with or without NAC. Cell cycle distribution was
      analyzed by flow cytometry and immunoblotting. NAC suppressed cell proliferation
      in a concentration-dependent manner, whereas NAC increased intracellular
      glutathione content significantly in a dose-dependent manner. The percentage of
      cells in the G1 phase after treatment with NAC was significantly higher than the
      percentage seen for control cells. Cyclin D1 expression of carcinoma cells
      treated with NAC decreased remarkably compared with cells without NAC treatment.
      Thus, the antiproliferative effect of NAC by prolongation of the G1 phase in
      human pancreatic carcinoma cells shows its possible utility as an antitumor
      agent.

PMID- 11329938
TI  - Analysis of DNA-ploidy using laser scanning cytometer in brain tumors and its
      clinical application.
AB  - There have been few reports on investigation of the cell kinetics of brain tumors
      using a laser scanning cytometer (LSC). We compared DNA analysis using a flow
      cytometer (FCM) with that by LSC using established cell lines of brain tumors,
      and we demonstrated the similarity of both analytical results. The DNA-index (DI)
      and proliferating index (PI) of various brain tumors were determined, and the
      results showed that these indices reflected the malignancy of the tumors. The DI
      values were higher for astrocytoma grade IV than for astrocytoma grade II,
      frequently showing an aneuploid pattern. The determination of DNA-ploidy using
      LSC, together with cryopathological diagnosis, was considered to be useful for
      deciding the area to be resected for glioma perioperatively and to be worth
      applying clinically.

PMID- 11329939
TI  - A new approach to develop a biohybrid artificial liver using a tightly regulated
      human hepatocyte cell line.
AB  - Currently patients with liver failure have been treated with a various liver
      support systems including a whole liver perfusion, a non-biological artificial
      liver, and a biohybrid artificial liver. In a hepatocyte-based bioreactor,
      porcine hepatocytes or transformed human liver tumor cells have been utilized
      because of the ease of preparation. According to the clinical data reported as of
      now, satisfactory results have not been obtained from the use of currently
      available liver support devices. One of the problems is limited availability of
      primary human liver cells for developing live support systems because of the
      shortage of human liver. To resolve this issue, human hepatocytes were
      immortalized with a retroviral vector SSR#69 which contained the genes of simian
      virus 40 large T antigen (SV40Tag) and herpes simplex virus-thymidine kinase (HSV
      TK). One of the immortal cell lines, NKNT-3, showed the gene expression of
      differentiated liver functions, grew steadily in chemically defined serum-free CS
      C medium, and doubled in number in about 48 hours. Essentially unlimited
      availability of NKNT-3 cells supports their clinical use for liver support
      devices. To realize the high density culture of NKNT-3 cells in a bioartificial
      liver device, we have developed cellulose microspheres (CMS) which contain cell
      adhesive GRGDS (Gly-Arg-Gly-Asp-Ser) peptides. Within 24 hours after starting a
      stirring suspension culture, GRGDS-CMS efficiently immobilized NKNT-3 cells. An
      electron microscopic examination demonstrated that NKNT-3 cells attached on GRGDS
      CMS had well-developed mitochondria, rough reticulums, and villous extensions. In
      this article, we review the history of extracorporeal liver support systems and
      describe an attractive strategy for developing a novel extracorporeal liver
      assist device using NKNT-3 cells and GRGDS-coated cellulose microspheres.

PMID- 11329940
TI  - Cloned mice derived from somatic cell nuclei.
AB  - In 1997, a cloned sheep "Dolly" was produced by nuclear transfer of somatic cell.
      The first birth of cloned mice derived from some somatic cells were succeeded in
      1998. At present, it is shown that somatic cells, cumulus cells, fibroblasts and
      Sertoli cells can be used to the study of cloned animal as nuclear donor. In this
      study investigation was designed to compare with efficiency on the production of
      cloned embryos by using the microinjection and the electrofusion methods for
      nuclear transfer. Oocyte enucleation was performed with a micromanipulator. The
      oocyte was held by holding pipette, and was enucleated using a beveled pipette.
      Microinjection method: Cell's nucleus injection was carried out by piezo
      micromanipulator. Cytochalasin B treated cumulus cell was aspirated into a
      injection pipette, and was broken its plasma membrane using the injection
      pipette. Then, the cumulus cell was injected into the enucleated ooplasm
      directly. Electrofusion method: The cell was aspirated into a beveled pipette,
      and then an aspirated cell was inserted into perivitelline space. Then, the pair
      of enucleated oocyte and cell was fused using electrical cell fusion apparatus.
      The reconstituted embryos were activated after nuclear transfer using St2+.
      Reconstituted embryos had been produced by the microinjection showed the
      embryonic development to over 8-cell stages. But, the rate of fragmentation of
      reconstituted embryos by the microinjection showed a little high rate in
      comparison with the electrofusion. When some reconstituted embryos by the
      microinjection were transplanted to pseudopregnant females' oviduct, 9 fetuses
      were observed at 14 days post coitum.

PMID- 11329941
TI  - [Contribution of progress in cytokine research to understanding vitreo-retinal
      diseases].

PMID- 11329942
TI  - [Autoimmune mechanisms in molecular pathology of glaucomatous optic neuropathy].
AB  - BACKGROUND: Glaucomatous optic neuropathy is characterized by loss of retinal
      ganglion cells and their axons, excavated appearance of the optic nerve head, and
      progressive loss of visual field sensitivity. In terms of pathology of the
      glaucomatous optic neuropathy, observations suggest retinal ganglion cell death
      by apoptosis. Deprivation of neurotrophic factors, ischemia, chronic elevation of
      glutamate, and disorganized nitric oxide metabolism have been suspected to be
      mechanisms triggering apoptosis. Another recent suggestion is that autoantibodies
      directed toward retinal antigens may be involved in facilitating apoptotic cell
      death in some glaucoma patients. METHOD: We summarized previous reports dealing
      with the relationship between glaucoma etiology and autoimmune responses, and
      investigated the contribution of autoimmune factors in glaucomatous optic
      neuropathy using electrophysiological and biochemical methods. RESULTS: We found
      serum anti-neuron specific enolase(NSE) antibody in approximately 20% of our
      glaucoma patients. In primary open angle glaucoma, maximum and mean intraocular
      pressures in antibody positive patients were significantly or relatively lower
      than pressures in antibody negative patients. In addition, we also found that
      apoptotic cell death of retinal ganglion cells was induced in rat eyes by
      intravitreal administration of purified anti-NSE antibody. CONCLUSION: As
      suggested by previous reports, autoimmune response is one of the mechanisms
      related to glaucoma etiology and NSE may have an important function as an
      autoantigen.

PMID- 11329943
TI  - [The role of cytokines in the pathogenesis of diabetic retinopathy].
AB  - PURPOSE: To investigate the role of cytokines and advanced glycation end
      products(AGEs) in the pathogenesis of diabetic retinopathy, we measured vascular
      endothelial growth factor(VEGF), interleukin-6(IL-6), tumor necrosis factor
      alpha(TNF-alpha), transforming growth factor-beta 1(TGF-beta 1), and
      pentosidine(an AGE) levels in aqueous, vitreous, and paired plasma obtained from
      diabetic patients. RESULTS: The aqueous levels of VEGF and IL-6 were positively
      correlated with the grade of clinical severity of diabetic retinopathy (both VEGF
      and IL-6, p < 0.001). Other cytokines and pentosidine levels were not
      significantly associated. The aqueous levels of VEGF and IL-6 were higher than
      the plasma levels(VEGF p = 0.02, IL-6 p < 0.001). CONCLUSION: Within the
      intraocular area VEGF and IL-6 are produced and participate in the pathogenesis
      of hyperpermeability of retinal vessels in preproliferative diabetic retinopathy.

PMID- 11329944
TI  - [Presynaptic effects of botulinum toxin type A on the neuronally evoked response
      of albino and pigmented rabbit iris sphincter and dilator muscles].
AB  - PURPOSE: To investigate the effects of botulinum toxin type A(botulinum A toxin)
      on the autonomic and other non-adrenergic, non-cholinergic nerve terminals.
      METHODS: The effects of neurotoxin on twitch contractions evoked by electrical
      field stimulation (EFS) were studied in isolated rabbit iris sphincter and
      dilator muscles using isometric tension recording. RESULTS: Botulinum A toxin(150
      nM) inhibited the fast cholinergic and slow substance P-ergic component of
      contraction evoked by EFS in the rabbit iris sphincter muscle without affecting
      the response to carbachol and substance P. Botulinum A toxin(150 nM) did not
      affect the twitch contraction evoked by EFS in the rabbit iris dilator muscle.
      CONCLUSION: These data indicated that botulinum A toxin may inhibit not only the
      acetylcholine release in the cholinergic nerve terminals, but also substance P
      release from the trigeminal nerve terminals of the rabbit iris sphincter muscle.
      However, neurotoxin has little effect on the adrenergic nerve terminals of the
      rabbit iris dilator muscle.

PMID- 11329945
TI  - [The effect of immunization with herpes simplex virus glycoprotein D fused with
      interluekin-2 against murine herpetic keratitis].
AB  - PURPOSE: To evaluate the effect of vaccination with fusion protein(gD-IL-2)
      consisting of herpes simplex type1(HSV-1) glycoprotein D(gD) and human
      interleukin-2(IL-2), and the effect of plasmid DNA vaccine encoding gD-IL-2
      against murine herpetic keratitis. METHODS: Plasmid containing gD-IL-2(pHDL-neol)
      was constructed, and gD-IL-2 peptide was purified. BALB/c mice were injected
      twice hypodermally or subconjunctivally with 1 microgram/0.1 ml of gD-IL-2
      peptide, or twice subconjunctivally with 90 micrograms/0.05 ml of gD-IL-2 plasmid
      DNA. Neutralizing antibody titer and delayed-type hypersensitivity (DTH) against
      HSV-1 were measured. Immunized mice were challenged with CHR3 strain of HSV-1 via
      the cornea. The clinical picture of epithelial and stromal keratitis was scored.
      RESULTS: Stromal keratitis was inhibited in gD-IL-2 peptide- or gD-IL-2 DNA
      immunized mice, but epithelial keratitis was not. It was confirmed that plasmid
      gD-IL-2 elicited significant serum virus neutralizing titer and DTH response.
      CONCLUSION: Vaccination with gD-IL-2 was effective against herpetic keratitis.

PMID- 11329946
TI  - [Effects of topical prostaglandin analogues on the aqueous flare intensity in
      rabbit eyes at an early phase of endotoxin-induced uveitis].
AB  - PURPOSE: We examined the effects of prostaglandin analogues on the blood-aqueous
      barrier(BAB) permeability in rabbit eyes at an early phase of endotoxin-induced
      uveitis(EIU). SUBJECTS AND METHODS: One drop of 0.005% latanoprost or 0.12%
      unoprostone were applied to rabbit eyes. Escherichia coli lipopolysaccharides
      were injected to induce uveitis. The changes in flare intensity in normal eyes
      and EIU eyes after application of eye drops were evaluated. The effect of
      cyclooxygenase inhibitor on the flare intensity changes caused by the application
      of unoprostone was also examined. RESULTS: Flare intensity increased
      significantly after a single instillation of unoprostone, and the increase was
      not prevented by pretreatment with cyclooxygenase inhibitor. In eyes with EIU,
      unoprostone caused an additional increase of flare intensity to uveitis induced
      flare change. Latanoprost had no effects on BAB in eyes with normal and with
      uveitic conditions. CONCLUSION: Latanoprost and unoprostone did not cause an
      excessive inflammatory reaction in rabbit eyes at an early phase of EIU.

PMID- 11329947
TI  - [Wound temperature during ultrasmall incision phacoemulsification].
AB  - PURPOSE: We studied the change in wound temperature during
      phacoemulsification(PEA) through an ultrasmall incision using an ultrasound tip
      with the infusion sleeve removed. METHODS: We observed an increase in the
      ultrasound tip temperature on thermographs when it was turned on under various
      conditions. We also measured the wound temperature using a thermometer during the
      use of ultrasound in PEA by occlusion when a 20 gauge ultrasound tip was inserted
      without an infusion sleeve into postmortem porcine eyes through a 19 gauge
      incision and when the infusion cannula was inserted through the side port.
      RESULTS: The ultrasound tip temperature did not rise if sufficient infusion
      liquid was circulated around the tip. When the 20 gauge ultrasound tip was used
      and the incision width was more than 1.5 mm, there was no thermal burn in the
      wound. CONCLUSION: Ultrasmall incision cataract surgery was conducted using a
      sleeveless ultrasound tip without the occurrence of a thermal burn in or around
      the incision wound.

PMID- 11329948
TI  - [Comparison of detectability of visual field abnormality by frequency doubling
      technology in primary open-angle glaucoma and normal-tension glaucoma].
AB  - PURPOSE: To compare the effectiveness of frequency doubling technology(FDT) in
      detecting abnormalities in primary open-angle glaucoma(POAG) and normal-tension
      glaucoma(NTG). SUBJECTS AND METHODS: Twenty-nine POAG patients (29 eyes) and 27
      NTG-patients(27 eyes) were studied. All subjects underwent testing with program C
      20 of FDT with appropriate corrective lenses. RESULTS: No significant differences
      were observed between the two groups in mean age, mean deviation(MD), and pattern
      standard deviation(PSD) measured by the Humphrey Field Analyzer(HFA). The
      correlation between MD values determined by HFA(x) and FDT(y) is represented by y
      = 0.60x - 2.7 (r = 0.78, p < 0.01) in the POAG group and y = 0.59x + 0.6 (r =
      0.81, p < 0.001) in the NTG group. No significant difference was found in the
      average PSD between the two groups. In early glaucoma cases (MD > or = -5 dB by
      HFA), a larger proportion of cases in the POAG group than the NTG group had a
      lower significance level of MD determined by FDT than by HFA (p < 0.02). At many
      test points on the temporal periphery in FDT the mean sensitivity was lower in
      the POAG group than in the NTG group; whereas no significant differences among
      HFA test points were observed. CONCLUSIONS: FDT detected visual field
      abnormalities in POAG cases more sensitively than in NTG cases. This finding
      indicates that the pathogenesis of My-cell damage is different in POAG and NTG.

PMID- 11329949
TI  - [Vitrectomy for diabetic cystoid macular edema].
AB  - PURPOSE: We evaluated the visual outcome of vitrectomy for diabetic cystoid
      macular edema. METHODS: Visual outcome and factors which may influence final
      visual acuity were assessed and documented retrospectively in 45 eyes of 40
      patients, all of whom were followed for at least 6 months postoperatively.
      RESULTS: Final postoperative visual acuity was two or more lines better than
      preoperative visual acuity in 58%, within one line in 40%, and had decreased by
      two lines or more in 2%. A final postoperative visual acuity of 0.5 or better was
      achieved in 38%. Preoperative visual acuity and the extent of the cystoid space
      on fluorescein angiography were significantly related to final visual acuity. A
      final postoperative visual acuity of 0.5 or better was noted in 8% of eyes with a
      preoperative visual acuity below 0.1, in 50% of eyes with preoperative visual
      acuity of 0.1 or better, in 71% of eyes with a cystoid space smaller than 5 disc
      areas, and in 20% of eyes with a cystoid space of 5 disc areas or more. The
      posterior vitreous membrane condition did not influence final visual acuity.
      There were no complications which decreased visual acuity. CONCLUSION: Based on
      the above results, we conclude that diabetic cystoid macular edema is a good
      indication for vitrectomy regardless of the posterior vitreous membrane
      condition. A preoperative visual acuity of 0.1 or better and/or a cystoid space
      smaller than 5 disc areas may be indications for surgery aimed at achieving a
      final postoperative visual acuity of 0.5 or better.

PMID- 11329950
TI  - [Objective evaluation of visual field loss in a patient with branch retinal
      artery occlusion and brain infarction].
AB  - PURPOSE: To evaluate visual field loss using multifocal ERG(m-ERG), multifocal
      VEP(m-VEP), and Heidelberg Retina Flowmeter(HRF) in a patient with branch retinal
      artery occlusion(BRAO) and brain infarction. CASE: A 38-year-old man noticed
      inferior-nasal visual field loss in the left eye, and was referred to Keio
      University Hospital. He suffered from paralysis in the left leg due to brain
      infarction at the age of 24. However, he had not noticed visual field loss due to
      the brain infarction. His left fundus showed retinal edema in the area of a
      superior-temporal retinal artery occulusion. He was diagnosed as having BRAO. The
      Goldmann and Humphry perimetric examinations revealed homonymous quadrantanopia
      in the upper left field as well as inferior visual field defect in the left eye.
      RESULTS: Both m-ERG and m-VEP, especially second-kernel responses, were reduced
      in the affected retinal area of BRAO. But only m-VEP was affected in the
      corresponding area of homonymous quadrantanopia in the upper left field. The
      retinal flow in the area with BRAO evaluated by HRF was decreased in some areas
      and not in others, suggesting that retinal function was not necessarily
      consistent with retinal circulation. CONCLUSIONS: m-ERG and m-VEP are useful To
      differentiate retinal lesions from brain lesions in visual field loss.

PMID- 11329951
TI  - [Epithelial scraping for corneal epithelial ingrowth after laser in situ
      keratomileusis].
AB  - BACKGROUND: Laser in situ keratomileusis (LASIK) is an effective method for
      correcting a wide range of myopia. However, complications sometimes occur. We
      report here a case treated with epithelial scraping two years and 4 months after
      surgery for epithelial ingrowth in the central cornea after LASIK. CASE: A 32
      year-old woman who had undergone LASIK one year and 4 months before visited our
      hospital because of visual loss. At the first examination in our clinic, her best
      corrected visual acuity was 20/60 in the right eye and 20/15 in the left eye.
      Epithelial ingrowth was observed in both eyes, but in the right eye, the
      epithelial ingrowth had reached the central cornea leading to the visual loss.
      The increased corneal stromal opacity decreased the visual acuity to 20/400. The
      patient decided to undergo epithelial scraping. The corneal flap was dissected
      again and epithelial scraping was performed on the stromal bed and back of the
      corneal flap. The visual acuity was improved from 20/400 to 20/40. However, the
      stromal opacity and the corneal astigmatism still remained. CONCLUSION: This case
      suggests that epithelial scraping should be performed immediately when ingrowing
      epithelium after LASIK begins to invade the central cornea.

PMID- 11329952
TI  - [Listener education].
AB  - Listener education has usually been conducted as primary prevention in
      occupational medicine. We report on the present state of listener education in
      which the training focuses on active listening (AL). AL means the way of
      listening to a person in the person-centered attitude (PCA) that is based on
      Rogers' three conditions, i.e. empathy, unconditional positive regard, and
      congruence. Although the need of this kind of training has been widely described,
      there is a paucity of academic literature on this subject. This review deals with
      listener education by dividing it into two types; one is listener education in a
      narrow sense that consistently depends on the three conditions, and the other is
      listener education in a broad sense that combines other methods that have
      different orientations from Rogers' theory. As an example of the former, Ikemi et
      al. reported the importance of the PCA, and studies conducted by Kubota et al.,
      Mishima et al., and Miyagi dealt with the actual training. As an example of the
      later, Morisaki and Hamaguchi et al. illustrated their training including other
      methods such as transactional analysis in their studies. Finally, we point out
      not only that future research needs to focus on the assessment of listener
      education, but also that AL needs to be understood from the standpoint of
      developing workers' competency.

PMID- 11329953
TI  - [Silent myocardial ischemia and exercise-induced arrhythmia detected by the
      exercise test in the total health promotion plan (THP)].
AB  - We investigated the prevalence and characteristics of ischemic heart disease
      especially silent myocardial ischemia (SMI) and arrhythmia in need of careful
      observation in the exercise stress tests in the Total Health Promotion Plan
      (THP), which was conducted between 1994-96 for the purpose of measuring
      cardiopulmonary function. All workers (n = 4,918, 4,426 males) aged 18-60 yr old
      in an occupational field were studied. Exercise tests with an ergometer were
      performed by the LOPS protocol, in which the maximal workload was set up as a
      presumed 70-80% maximal oxygen intake, or STEP (original multistage protocol).
      ECG changes were evaluated with a CC5 lead. Two hundred and fifteen people
      refused the study because of a common cold, lumbago and so on. Of 4,703 subjects,
      17 with abnormal rest ECG and 19 with probable anginal pain were excluded from
      the exercise tests. Of 4,667 who underwent the exercise test, 37 (0.79%) had
      ischemic ECG change, and 155 (3.32%) had striking arrhythmia. These 228 subjects
      then did a treadmill exercise test with Bruce protocol. Twenty-two (0.47% of
      4,703) showed positive ECG change, 9 (0.19%) of 22 had abnormal findings on a
      201Tl scan. 8 (0.17%) were diagnosed as SMI (Cohn I), in which the prevalence of
      hypertension, hyperlipidemia, diabetes mellitus, smoker and positive familial
      history of ischemic heart disease was greater than that of all subjects. In a 15
      30 month follow up, none has developed cardiac accidents. Exercise-induced
      arrhythmia was detected in 11 (0.23%) subjects. Four were non-sustained
      ventricular tachycardia without any organic disease, 4 were ventricular
      arrhythmia based on cardiomyopathy detected by echocardiography, 2 were atrial
      fibrillation and another was WPW syndrome. It is therefore likely that the
      ergometer exercise test in THP was effective in preventing sudden death caused by
      ischemic heart disease or striking arrhythmia.

PMID- 11329954
TI  - [Evaluation of bone metastases from renal cell carcinoma].
AB  - Forty-two cases of bone metastasis from renal cell carcinoma were examined.
      Thirty of the cases had bone metastases at the time of renal cell carcinoma. Bone
      metastasis appeared after treatment of the primary site in 12 cases. Fifteen
      cases had only bone metastasis and another 27 had metastasis in multiple organs.
      The total cause-specific survival curve of these patients was 10% at 5 years. All
      patients with bone metastases died of cancer within 5 years after the bone
      metastases had developed. There was no significant difference in the survival
      rate between patients with bone metastases and patients with lung metastases. We
      investigated the prognostic value of laboratory studies in bone metastases of
      renal cell carcinoma. However, no significant markers were detected for bone
      metastases. The 6 patients were treated with decompressed laminectomy (2), wide
      resection (3) and excision of the metastatic lesions (3). The quality of life was
      improved in all the patients although they died of cancer.

PMID- 11329955
TI  - [Clinical study on renal trauma].
AB  - A total of 64 patients with renal trauma were treated at the Department of
      Urology, St. Marianna University School of Medicine, from January 1988 to
      December 1996. Patients were between 3 and 66 years old (mean 28.2); 56 (87.5%)
      of them were male and 8 (12.5%) were female. The main cause of injury was a
      traffic accident in 33 cases (51.6%). According to the Classification of Renal
      Injury by the Japanese Association for the Surgery of Trauma in Japan, there were
      27 cases (42.2%) of Type I (subcapsular injury), 12 cases (18.8%) of Type II
      (superficial injury), 16 cases (25.0%) of Type III (Deep injury), 6 cases (9.4%)
      of Type IV (Pedicle injury). Surgical treatment was performed in 6 cases (9.3%).
      The major associated injuries were bone fracture in 33 cases (51.6%), lung injury
      in 20 cases (31.3%) and liver injury in 16 cases (25.0%). The literature is also
      reviewed briefly.

PMID- 11329956
TI  - [Clinical outcome and analysis of radical prostatectomy in clinical stage B and C
      prostate cancer].
AB  - Between 1989 and 1999, 40 patients treated with radical prostatectomy for
      clinical stage B and C prostate cancer were analyzed. Prostate-specific antigen
      (PSA) failure after radical prostatectomy occurred in four patients, and one of
      them died of clinical recurrence of prostate cancer. Cause-specific survival at 5
      years was 91.7% and PSA failure-free rate at 5 years was 76.8%. Staging accuracy
      of CT and MRI image was not satisfactory. In 41.7% patients, extracapsular
      extension can not be determined. Preoperative serum PSA levels of pathologically
      organ-confined disease (OCD) patients were significantly lower than those of
      pathologically non-OCD patients. Further analysis indicated that preoperative
      serum PSA levels of greater than 20.1 ng/ml are useful predictors for
      pathologically non-OCD.

PMID- 11329957
TI  - [Predictive value of prostate specific antigen density in the detection of
      prostate cancer in patients with elevated prostate specific antigen levels and
      normal digital rectal findings or stage A prostate cancer].
AB  - We compared the usefulness of PSA and PSA density (PSAD) in diagnosing prostate
      cancer in 102 men who had a PSA value higher than 4.0 ng/ml and normal digital
      rectal examination and who had undergone transrectal ultrasonography-guided
      systematic sextant biopsies of the prostate between August 1996 and October 1999.
      In addition, for a group of 53 patients who underwent retropubic simple
      prostatectomy, PSA, PSAD and PSA transition zone (PSA-TZ) examination results for
      those with stage A prostate cancer were compared with the results for those with
      benign prostatic hyperplasia (BPH). Of the former 102 men, 20 (19.6%) had
      prostate cancer. There was no significant difference in mean PSA level between
      patients with negative and those with positive biopsy results (mean 9.3 and 11.8,
      respectively, p = 0.295), but the mean PSAD of patients with positive biopsy
      results was significantly higher than that of those with negative results (mean
      0.55 and 0.29, respectively, p = 0.0007). Of the 53 men who underwent retropubic
      simple prostatectomy, 10 (18.9%) were diagnosed with stage A prostate cancer.
      There was no significant difference in mean PSA, PSAD and PSA-TZ examination
      results between patients with BPH and those with stage A prostate cancer. For all
      102 patients and for 71 patients with PSA levels of 4.1-10.0 ng/ml, a PSAD cutoff
      value of 0.1 reduced the number of biopsies 15.7% (16 of 102 cases), and 22.5%
      (16 of 71 cases), respectively. These results suggest that by measurement of PSAD
      some patients with benign disease could be spared a biopsy which would have been
      performed based on PSA results alone.

PMID- 11329959
TI  - [A case of clinically multifocal renal cell carcinoma].
AB  - A 61-year-old woman was diagnosed with a renal tumor of the left kidney by
      ultrasound sonography during a health check-up. Computerized tomography (CT) and
      colored Doppler ultrasound sonography demonstrated two hypervascular tumors as
      typical renal cell carcinomas. A radically nephrectomized specimen was step
      sectioned. Four tumor nodules were detected macroscopically, and 47 small nodules
      were detected microscopically, showing the clear cell type and alveolar growth
      pattern. Then all nodules including the 47 small nodules were diagnosed renal
      cell carcinoma.

PMID- 11329958
TI  - [A case of renal cell carcinoma diagnosed by MAG3 scintigraphy because of
      moderate renal dysfunction].
AB  - An 84-year-old man presented at our hospital with complaints of severe gross
      hematuria and lower right abdominal pain. A right renal mass was detected by
      ultrasound sonography and plain computerized tomography (CT) scan, but an exact
      diagnosis was not obtained. Because the patient presented with moderate renal
      dysfunction and severe gross hematuria, we were unable to perform imaging studies
      using contrast material or ureteroscopic instruments. Finally,
      mercaptoacetylglycyl-glycylglycine (MAG3) scintigraphy and magnetic resonance
      imaging (MRI) demonstrated renal cell carcinoma, and we performed transarterial
      embolization (TAE) therapy using ethanol and gel foam. Based on their efficacy
      and noninvasiveness, we conclude that MAG3 scintigraphy and MRI are the optimal
      modalities for imaging in patients with renal dysfunction.

PMID- 11329960
TI  - [A case of collecting duct carcinoma (Bellini duct carcinoma) producing
      carcinoembryonic antigen].
AB  - We report a case of collecting duct carcinoma (Bellini duct carcinoma) producing
      carcinoembryonic antigen (CEA). A 61-year-old man visited our hospital because of
      a left renal mass detected by ultrasonography in an other hospital. Computed
      tomography showed a low density tumor measuring about 3 cm in the left kidney.
      Angiography demonstrated a hypovascular tumor. The serum level of CEA was
      increased to 20 ng/ml. (normal < 7 ng/ml). Left radical nephrectomy was
      performed. Histological examination revealed collecting duct carcinoma with
      papillary growth (T1aN1M0). Cancer cells showed a positive immunohistochemical
      staining for CEA. Under a diagnosis of CEA-producing collecting duct carcinoma of
      the left kidney, the patient underwent systemic chemotherapy (M-VAC). The serum
      level of CEA decreased to the normal level after the nephrectomy, but six months
      postoperatively, metastatic bone tumor at the left pelvic bone was revealed on
      the plain film and at the same time, the CEA level was increased again.

PMID- 11329961
TI  - [Adenocarcinoma of the renal pelvis and transitional cell carcinoma of the ureter
      occurring 11 years after radical cystectomy for bladder cancer: a case report].
AB  - We report a case of upper urinary tract carcinoma which recurred 11 years after
      total cystectomy. A 52-year-old man presented with complaints of a sense of
      residual urine and terminal miction pain. Urinary cytology, cystoscopic
      examination and intravenous pyelography revealed normal findings. Twenty months
      later, because class V urinary cytologic findings were detected, transurethral
      biopsy was performed. Carcinoma in situ was diagnosed pathologically. Therefore,
      total cystectomy and ileal conduit urinary diversion were performed. The
      pathological diagnosis was transitional cell carcinoma, grade 3, pTis. At 127
      months postoperatively, laboratory examination revealed an extremely high serum
      level of LDH (3,084 U/l). The right kidney was not visualized on IVP and computed
      tomography revealed a right renal irregular mass. On the suspicion of a renal
      pelvic tumor, right total nephroureterectomy was done. The pathologic diagnosis
      was renal pelvic adenocarcinoma and ureteral transitional cell carcinoma. The
      patient was treated postoperatively with 3 cycles of systemic chemotherapy and
      radiotherapy. The serum level of LDH returned to normal. However, one year later,
      the serum level of LDH elevated to 1,118 U/l. He died of retroperitoneal lymph
      node, left adrenal gland and pulmonary metastases.

PMID- 11329962
TI  - CA19-9-producing transitional cell carcinoma of the renal pelvis: a case report.
AB  - We report a case of CA19-9-producing transitional cell carcinoma of the renal
      pelvis. A 59-year-old male patient with left hydronephrosis was referred to us
      from a local physician. Retrograde pyelogram revealed irregular filling defects
      involving calices, pelvis and proximal ureter. The serum CA19-9 level was
      elevated. Under the diagnosis of renal pelvic tumor, we performed radical left
      nephroureterectomy. The tumor was histologically diagnosed as transitional cell
      carcinoma. The tumor cells showed positive immunostaining for CA19-9. The serum
      CA19-9 level was normalized after the operation. To our knowledge, this is the
      28th case of a CA19-9-producing tumor in the Japanese literature.

PMID- 11329963
TI  - [A case of ureterovesical malacoplakia that manifested hydronephrosis].
AB  - A 70-year-old woman visited a nearby physician with a chief complaint of fever
      and was admitted to a hospital with a diagnosis of acute pyelonephritis. After
      discharge, pyuria persisted and examination revealed an intravesical solid tumor.
      The patient was referred to this department for close examination and treatment.
      The right kidney was hydronephrotic. The intravesical tumor that was resected was
      solid yellowish-white and ranged from the neck of the uterus to both ureteral
      orifices. In addition, a grain-sized tumoral lesion, was found in the lower part
      of the ureter and was also resected. There was sclerotic thickening localized to
      the right intramural ureter, which had a slightly edematous interior. This was
      considered to be the cause of the hydronephrosis and a ureteral stent was put in
      place. Pathological diagnosis was given as malacoplakia. With this case,
      placement of a ureteral stent was chosen based on the findings of a minimal
      ureteral lesion, a narrow area of scarring in the intramural ureter as a probable
      cause of hydronephrosis, and a judgement of mild obstruction. A stent is less
      invasive for patients, but consideration should be given to urinary infection due
      to long-term placement recurrence of malacoplakia due to the increased risk of
      infection, and trouble with periodical exchanging of catheters due to aggravated
      scarring. Absence of pyuria or signs of recurrence after seven months' placement
      suggests that use of the stent was the best method.

PMID- 11329964
TI  - [Prostate cancer associated with hemorrhagic cyst: a case report].
AB  - A 68-year-old man consulted our department for sudden onset of dysuria and
      perineal pain. On digital rectal examination, soft and a hen-egg-sized mass was
      palpated. Serum PSA value was elevated to 11.4 ng/ml. Pelvic magnetic resonance
      imaging (MRI) suggested a large hemorrhagic cyst associated with prostate cancer.
      In addition to a pathological diagnosis as poorly differentiated adenocarcinoma
      (Gleason grade 5/4), which was established by transurethral biopsy, aspirated
      cyst contents revealed an elevated PSA value (3,090 ng/ml). Clinical staging was
      determined as T4N0M0. Following administration of androgen-deprivation therapy
      for 3 months, radiation therapy (64 Gy) was administered to the prostate. Twelve
      months after the diagnosis, the serum PSA value has remained within normal
      limits, and no local recurrence of the disease was detected.

PMID- 11329965
TI  - [Seminal vesicle cyst with ipsilateral renal agenesis: a case report].
AB  - A 26-year-old man was referred to our hospital for further evaluation of a cystic
      lesion in the pelvis. He was completely asymptomatic, although he experienced
      gross hematuria 10 months before his visit. Drip infusion pyelography (DIP) and
      abdominal computerized tomography (CT) showed a cystic structure behind the
      bladder and absence of the left kidney. Transrectal ultrasonography (TRUS)
      suggested left ejaculatory duct obstruction and seminal vesicle deformity. On
      cystoscopy a large bulging mass under the left side of the bladder was seen. The
      left half of the trigone and left ureteral orifice were absent.
      Vasovesiculography demonstrated dilated and tortuous left seminal vesicle. Three
      days after this procedure, the patient suffered left epididymitis. It did not
      respond rapidly to antibiotic therapy, so percutaneous drainage of the cyst was
      performed. He has been completely free of symptoms and no seminal vesicle cysts
      have been detected on TRUS at five months follow-up.

PMID- 11329966
TI  - [Female paraurethral cyst: a case report].
AB  - We experienced a case of paraurethral cyst in a 42-year-old woman. A paraurethral
      cyst, the diameter of which was about 2 cm, was observed in the septum between
      urethra and vagina. No communication between the cyst and urthra or vagina was
      detected. The resected cyst did not reveal malignant findings. Sixty-one cases of
      paraurethral cyst in the Japanese literature are also reviewed.

PMID- 11329967
TI  - [A case of polyarteritis nodosa presenting as a mass in scrotum].
AB  - A 16-year-old boy with a painful tumor in the left scrotum was referred to our
      department. CT scans showed a low density area in the left testis, so we
      diagnosed a left testicular tumor and performed left inguinal orchiectomy.
      Histological examination revealed polyarteritis nodosa (PN) of the testis and
      epididymis. Systemic examination revealed no other evidence of PN. Although
      induration developed in the right epididymis after the operation, it resolved
      with steroid therapy. The patient is currently asymptomatic and is being followed
      at our clinic. The pathogenesis and management of this rare condition are
      discussed.

PMID- 11329968
TI  - Hospitalists' leadership key to IOM's 21st century aims.

PMID- 11329969
TI  - Developing Internet strategies is a top priority for hospital systems.

PMID- 11329970
TI  - MedPAC's report to Congress paints a better profit picture for hospitals.

PMID- 11329971
TI  - Web-based data analysis tools help providers, MCOs contain costs.

PMID- 11329972
TI  - Winning higher rates will be harder this year.

PMID- 11329973
TI  - IOM committee on quality outlines its aims and 'rules' for health care.

PMID- 11329974
TI  - 23% of COPD patients say the disease makes them an invalid.

PMID- 11329975
TI  - PTCA catheter prices move down.

PMID- 11329976
TI  - Hospitals deal with blood shortages, filtration cost.

PMID- 11329977
TI  - Storage units produce $1 million in savings.

PMID- 11329978
TI  - The only thing certain: large changes lurk for case management's future.
AB  - The question has never been whether health care will change. Its evolution is
      continual, and predictions about its future often are about as accurate as 1930s
      science fiction. Even so, several trends already have emerged that some experts
      claim provide an interesting glimpse of what's to come--both in case management
      and in the industry at large.

PMID- 11329979
TI  - IOM's wish list: sweeping changes in health care quality.
AB  - Recently, the institute of Medicine's Committee on the Quality of Health Care in
      America publicly released its wish list for the future. It gives several specific
      recommendations for the direction health care should take, including a proposal
      that Congress create a $1 billion 'innovation fund' to improve the current system
      that it says is 'beset by serious problems'.

PMID- 11329980
TI  - CMs respond to national caseload survey.
AB  - More than 500 case managers responded to the exclusive national survey conducted
      by American Health Consultants, publisher of Hospital Case Management, and the
      Case Management Society of America in December 2000. Here, for the first time,
      see the initial results of the survey, which attempts to define the much-debated
      caseload issue.

PMID- 11329981
TI  - Need help sorting out observation status?
AB  - You're not alone if you've experienced difficulty sorting out the rules of
      observation status. The limits are different between Medicare and private
      insurance companies, creating frustration and extra paperwork for case managers.

PMID- 11329982
TI  - Laparoscopic nephrectomy pathway sees great outcomes.

PMID- 11329983
TI  - Elusive cancer-related fatigue is easy to conquer.

PMID- 11329984
TI  - For safety's sake, bill aims to eliminate overtime.
AB  - House Bill 78 was introduced in the Ohio state legislature with the support of
      Rep. Ann Womer Benjamin (R-District 75) and of the Ohio Nurses Association (ONA).
      'This is not the first attempt to address staffing by any means, but it is the
      first comprehensive bill,' says Peggy Noble, RN, government affairs specialist
      for the ONA. It calls for periodic review of staffing policies and no overtime
      for nurses.

PMID- 11329985
TI  - Reducing emergency visits in older adults with chronic illness. A randomized,
      controlled trial of group visits.
AB  - CONTEXT: Emergency department utilization by chronically ill older adults may be
      an important sentinel event signifying a breakdown in care coordination. A
      primary care group visit (i.e., several patients meeting together with the
      provider at the same time) may reduce fragmentation of care and subsequent
      emergency department utilization. OBJECTIVE: To determine whether primary care
      group visits reduce emergency department utilization in chronically ill older
      adults. DESIGN: Randomized trial conducted over a 2-year period. SETTING: Group
      model HMO in Denver, Colorado. PATIENTS: 295 older adults (> or = 60 years of
      age) with frequent utilization of outpatient services and one or more chronic
      illnesses. INTERVENTION: Monthly group visits (generally 8 to 12 patients) with a
      primary care physician, nurse, and pharmacist held in 19 physician practices.
      Visits emphasized self-management of chronic illness, peer support, and regular
      contact with the primary care team. MEASURES: Emergency department visits,
      hospitalizations, and primary care visits. RESULTS: On average, patients in the
      intervention group attended 10.6 group visits during the 2-year study period.
      These patients averaged fewer emergency department visits (0.65 vs. 1.08 visits;
      P = 0.005) and were less likely to have any emergency department visits (34.9%
      vs. 52.4%; P = 0.003) than controls. These differences remained statistically
      significant after controlling for demographic factors, comorbid conditions,
      functional status, and prior utilization. Adjusted mean difference in visits was 
      0.42 visits (95% CI, -0.13 to -0.72), and adjusted RR for any emergency
      department visit was 0.64 (CI, 0.44 to 0.86). CONCLUSION: Monthly group visits
      reduce emergency department utilization for chronically ill older adults.

PMID- 11329987
TI  - Deferred care for adults with musculoskeletal complaints.
AB  - CONTEXT: Many ambulatory care facilities do not have resources to provide same
      day care for all walk-in patients. Yet, there are few guidelines that identify
      patients for whom care can be safely deferred. OBJECTIVE: To describe the
      development and implementation of deferred-care guidelines for adults with
      musculoskeletal complaints. DESIGN: Consensus process and field test. GUIDELINE
      DEVELOPMENT: After an eight-member multidisciplinary physician panel identified
      critical factors that necessitate same-day care, we created 34 clinical scenarios
      to consider for deferred care. In 22 scenarios, the panel members agreed that
      deferred care was safe. These were formatted into screening guidelines for back,
      neck, isolated extremity, and generalized muscle pain. IMPLEMENTATION: In
      reliability testing between two nurses reading 40 patient scenarios, interrater
      agreement for deferred care was nearly perfect (kappa = 0.95). The guidelines
      were then applied to 448 patients presenting with musculoskeletal complaints to a
      Veterans Administration ambulatory care triage station. One hundred seven (24%)
      patients met guidelines for deferred care. Seventy-six patients agreed to have
      their care deferred, of which 66 kept their return appointment. CONCLUSIONS: Our
      guidelines suggest that a substantial proportion of patients with musculoskeletal
      complaints can have their care deferred. Most patients were willing to do so and
      kept their follow-up appointment. Use of these guidelines could help decompress
      ambulatory settings with limited resources to provide nonemergency same-day care.

PMID- 11329986
TI  - Misleading presentation of breast cancer in popular magazines.
AB  - CONTEXT: Women commonly misunderstand their risk for breast cancer,
      overestimating both their risk for developing the disease at a young age and
      their lifetime risk. OBJECTIVE: To determine whether age bias occurs in popular
      media coverage of breast cancer. SELECTION STRATEGY: The search term breast
      cancer was used to identify 389 articles in U.S. magazines with a circulation of
      at least 500,000 published between January 1, 1993, and June 30, 1997. MAIN
      OUTCOME MEASURES: Presence of age-related themes and age of patients with breast
      cancer who were described in vignettes. RESULTS: Age-related themes included
      breast cancer as a cause of premature death, breast cancer in mothers of young
      children, and the impact of a breast cancer diagnosis on dating and marriage.
      Factual information about age as a risk factor for breast cancer was presented in
      only 14% of articles, and age was often included in vignettes describing a woman
      with breast cancer. Thirty-four percent of the articles included one or more
      breast cancer vignettes. These articles included 172 unique vignettes in which
      patient age was described. In 84% of the vignettes (144 of 172), women were
      diagnosed with breast cancer before 50 years of age; in 47% (80 of 172), women
      were diagnosed before 40 years of age. On the basis of the age-specific incidence
      of breast cancer in the United States, the expected percentages would be 16% and
      3.6%, respectively. CONCLUSIONS: Stories about breast cancer in popular U.S.
      magazines misrepresent the age distribution of the disease, emphasizing atypical
      cases of early-onset breast cancer and their social consequences. This
      presentation of breast cancer may contribute to women's fears of breast cancer
      and to overestimates of personal risk.

PMID- 11329988
TI  - The case for persuasive health messages.

PMID- 11329989
TI  - The case for letting information speak for itself.

PMID- 11329990
TI  - Number fifteen.

PMID- 11329991
TI  - Assessing hospital quality: a review for clinicians.

PMID- 11329992
TI  - Are we overvaluing performance measures?

PMID- 11329993
TI  - Promoting self-referral for advanced imaging.

PMID- 11329994
TI  - A longitudinal study of adolescent mental health service use.
AB  - This study examines longitudinal mental health service use patterns of a school
      based sample of adolescents. Based on the Center for Epidemiologic Studies
      Depression Scale scores, a stratified sample of middle-school students was
      interviewed using the Schedule for Affective Disorders and Schizophrenia for
      School-Aged Children: cycle one (n = 579; mean age 12.83) and cycle two (n = 490;
      mean age 18.65). Service use also was assessed by mailed questionnaire: cycle
      three (n = 330; mean age 20.60). Service use decreased over time. Whites and
      males received significantly more treatment in the first cycle. In the second
      cycle, service use by race and gender was equal; in the third cycle, females
      received more treatment. Those with a psychiatric diagnosis (first cycle, 54%;
      second cycle, 33%) received treatment in the prior year. Under-treatment of youth
      with psychiatric diagnoses is a significant problem, with differences in service
      use by race and gender over time.

PMID- 11329995
TI  - Needs-based planning for persons with serious mental illness residing in
      intermediate care facilities.
AB  - This study examined the association of clinical status to mental health service
      use among persons with mental illness living in residential care. Two hundred
      residents with a chart diagnosis of schizophrenia were randomly selected from
      four intermediate care facilities. The severity of psychiatric illness-community
      mental health (SPI-CMH) scale was used to assess clinical status and symptom
      severity according to three dimensions: symptoms and functioning, risk behaviors,
      and complication to illness. Lower levels of severity of psychiatric illness were
      associated with participation in workshops, family contact, and admitting to
      mental health problems. Results suggest that residents of the intermediate care
      facilities have clinical needs consistent with habilitation and rehabilitation
      services. While residents infrequently engage in high-risk behavior such as
      suicide and violence, they have considerable living skills and vocational needs.
      Future research should consider the relationship over time of mental health
      service utilization, severity of psychiatric illness, and psychosocial factors.

PMID- 11329996
TI  - Managed care and outpatient substance abuse treatment intensity.
AB  - This study examines the extent to which managed care behavioral controls are
      associated with treatment intensity in outpatient substance abuse treatment
      facilities. Data are from the 1995 National Drug Abuse Treatment System Survey, a
      nationally representative survey that includes over 600 provider organizations
      with a response rate of 86%. Treatment intensity is measured in three ways: (1)
      the number of months clients spend in outpatient drug treatment, (2) the number
      of individual treatment sessions clients receive over the course of treatment,
      and (3) the number of group treatment sessions clients receive over the course of
      treatment. After accounting for selection bias and controlling for market,
      organization, and client characteristics, there is no significant relationship
      between the scope of managed care oversight and treatment intensity. However, the
      stringency of managed care oversight activities is negatively associated with the
      number of individual and group treatment sessions received over the course of
      treatment.

PMID- 11329997
TI  - ADHD treatment in a behavioral health care carve-out: medications, providers, and
      service utilization.
AB  - Children's mental health services are increasingly being managed by managed
      behavioral health organizations (MBHOs) through carve-outs. Little information is
      available, however, about services and interventions being received by children
      whose mental health benefits are carved out. Using claims data, this study
      explores the treatment of children with a common child psychiatric disorder,
      attention deficit hyperactivity disorder (ADHD). Children being treated for ADHD
      see a variety of provider combinations. Children diagnosed with comorbid mood or
      anxiety disorders are more likely to see a psychiatrist than a primary care
      physician or therapist, and they are more likely to be in treatment with both a
      psychiatrist and a therapist than with just one mental health professional. After
      controlling for severity indicators, costs were significantly lower for patients
      being treated by just a psychiatrist than for patients seeing both a psychiatrist
      and therapist. This finding raises the possibility that attempts to save money by
      "splitting treatment" may not be cost-effective.

PMID- 11329998
TI  - The long-term treatment outcomes of depression and anxiety comorbid with
      substance abuse.
AB  - The impact of the comorbidity of psychiatric disorder and substance abuse on
      treatment outcomes was estimated using data from a longitudinal survey of 1,920
      individuals who were followed nearly 15 years. Individuals with anxiety or
      depression symptoms at baseline generally experienced increased distress at
      follow-up; those who received mental health treatment experienced decreased
      distress at follow-up. Individuals with substance abuse/dependence symptoms who
      received treatment at baseline had a higher risk of follow-up disability; treated
      individuals with substance abuse who had comorbid anxiety and depression symptoms
      at baseline were at lower risk of disability at follow-up. Individuals with
      anxiety and depression symptoms at baseline had a higher incidence of chronic
      illness during follow-up; those who received treatment or had substance abuse
      symptoms did not. The results may improve understanding of the degree to which
      treatment of a primary disorder may prevent the incidence or reduce the
      prevalence of a secondary comorbid disorder.

PMID- 11329999
TI  - Impact of VA bed closures on use of state psychiatric services.
AB  - This study examined whether inpatient bed reductions at a Department of Veterans
      Affairs (VA) medical center increased VA patients' use of state mental health
      agency services. Veterans residing in two Connecticut cities who used VA
      psychiatric services during fiscal years 1993 through 1998 (n = 2,943) were
      identified from computerized files. Then their records were merged with state
      files. Coinciding with the time of VA bed closures, the proportion of VA patients
      who used any state services increased from 2.6%, 2.8%, and 2.7% from 1993 through
      1995 to 3.6%, 3.5%, and 3.6% from 1996 through 1998 (p < .03). These changes
      reflect increased likelihood of state outpatient service use, but not inpatient
      services. No statistically significant changes occurred in the cost of state
      services used by VA patients. Bed closure impact may be reflected in increased
      cross-system service use, which may be a useful indicator of unmet needs
      resulting from system changes.

PMID- 11330000
TI  - Needs-based planning: evaluation of a level-of-care planning model.
AB  - With the closure of a number of provincial psychiatric hospitals planned, the
      Ministry of Health of Ontario has commissioned a series of planning projects to
      identify alternative placements for current hospital patients. The goal is to
      match need to care in the least restrictive setting. A systematic, clinically
      driven planning process was implemented that involved three steps: development of
      a continuum of levels of care representing increasingly intensive and more
      restrictive supports, development of criteria and decision rules for placement,
      and comprehensive needs assessment of current patients using the Colorado Client
      Assessment Record. Results showed that only 10% of current inpatients need to
      remain in the hospital, and over 60% could live independently in the community
      with appropriate supports. Evidence supports concurrent validity of the planning
      model, but further work is needed to assess whether recommended levels of care
      effectively meet consumer needs in the least restrictive setting.

PMID- 11330001
TI  - Are barriers to mental health and substance abuse care still rising?
AB  - This study estimates unmet need and barriers to alcohol, drug, and mental health
      (ADM) services in 1997 to 1998 using data from a national household survey (n =
      9,585). In 1997 to 1998, 10.9% of the population perceived a need for ADM
      services, with 15% obtaining no treatment and 11% experiencing delays or
      obtaining less care than needed. The rate of unmet need due to no treatment is
      similar to earlier studies, but the group experiencing delays/less care is almost
      as large. This finding emphasizes the importance of defining access to care more
      broadly by including timeliness and intensity of care. Economic barriers are
      highest for the uninsured, but also are high among the privately insured.
      Individuals with unmet need are significantly more likely to use complementary
      and alternative medicine (CAM). Those with no conventional mental health care
      rely on self-administered treatment, while those with delayed/insufficient
      conventional care use CAM providers and self-administered treatment.

PMID- 11330002
TI  - The mental health orientation of juvenile courts.
AB  - Effective systems of care for youth with emotional disorders require shared
      values among stakeholders toward a variety of mental health issues. Juvenile
      courts represent one stakeholder group whose values can affect the delivery of
      services to young offenders with or at risk of emotional disturbances. This
      research uses statewide data from Tennessee to assess the mental health
      orientation (MHO) of juvenile courts, their use of treatment options for
      offenders, and whether MHO influences the treatment referral decision. Results
      show that courts have a positive MHO, but this subjective orientation does not
      correspond to higher treatment referral rates. Moreover, service referrals are at
      a considerably lower rate than estimates of need for this population of youth
      would predict. While positive MHO suggests a basis for nurturing the shared
      vision required for effective systems of care, other factors must be considered
      to account for courts' underutilization of treatment options for juvenile
      offenders.

PMID- 11330004
TI  - Don't overlook impact of stress on medical costs.

PMID- 11330003
TI  - Outcome following child psychiatric hospitalization.
AB  - Admission, discharge, and follow-up evaluations of 110 children admitted to a
      child psychiatric unit (mean 14 days) showed that the children's psychological
      functioning improved significantly during hospitalization. Gains were not fully
      maintained at follow-up (1 and 6 months), but the children were still
      significantly less impaired after discharge than at admission. A nonsignificant
      difference existed between follow-up scores, indicating no loss of progress or
      decline in functioning from 1- to 6-month follow-up. The results are consistent
      with an ABA (A = no inpatient intervention, B = inpatient intervention, A = no
      inpatient intervention) treatment effect. They are not explained by removal from
      and return to an unsatisfactory home environment. Psychological functioning after
      admission was significantly better than after 1 to 6 months of post-discharge
      psychiatric services. This study offers a clinically feasible approach to
      evidence-based practice by documenting patient improvement during and after
      inpatient treatment using a simple, empirically supported assessment instrument.

PMID- 11330005
TI  - Study examines weapons in fight to control drug costs.

PMID- 11330006
TI  - Data nail down the astounding cost of diabetes-related care.

PMID- 11330007
TI  - Childhood immunization rates up, but other health indicators lag.

PMID- 11330008
TI  - Poor folk: some characters of Dostoevsky.

PMID- 11330009
TI  - Facing "O": Wilfred Bion, Emmanuel Levinas, and the face of the other.

PMID- 11330010
TI  - Hegel on projective identification: implications for Klein, Bion, and beyond.

PMID- 11330011
TI  - A case of (mis)taken identity? I: The question of Freudian discourse.

PMID- 11330012
TI  - The dreams of a cancer patient: a "royal road" to understanding the somatic
      illness.
AB  - In this paper we have presented the principal dreams of a 39-year-old female
      patient in order to demonstrate how closely the dreams were linked with the
      understanding of her cancerous condition. The analysis, lasting over a period of
      eight years, ended with the remission of the patient's cancerous condition to the
      point where she was without pain and symptom-free. The findings suggested that
      her dreams played a special role in her analysis by providing important landmarks
      regarding her treatment's progress and state of her cancerous condition. In a
      general sense, it was concluded that the patient's dreams did provide a "royal
      road" to understanding her somatic illness. Specifically, it was concluded that,
      first, the patient's dreams were able to represent quite reliably, in symbolic
      form, the state of her cancerous condition; second, that the cancer condition and
      transference-countertransference reactions were closely entwined; and third, that
      each of the patient's dreams seemed to be introduced by a crisis situation
      connected with a traumatic early memory.

PMID- 11330013
TI  - Emerging issues with mentally ill offenders: causes and social consequences.
AB  - Persons with mental illness and co-occurring substance abuse disorders are
      incarcerated at disproportionately high rates in comparison to the general
      population. Reasons may include high standards for involuntary commitment, an
      overall increase in substance abuse and the policy of deinstitutionalization.
      However, one significant reason may be that psychiatric institutions serve a
      social control function, which has not been appreciated by policymakers and
      program developers since deinstitutionalization. This paper presents provider
      views of the population and issues of concern for clients, families, and the
      agencies. Discussion includes service-provider response to the population, new
      program models, and implications for policymakers.

PMID- 11330014
TI  - Mental health and substance abuse services in ten state Medicaid programs.
AB  - Program data for 1993 on Medicaid mental health and substance abuse (MH/SA)
      services and expenditures were developed from Health Care Financing
      Administration (HCFA) research files for 10 states. These data show that MH/SA
      service users are 7 to 13% of Medicaid enrollees. The percentage of Medicaid
      enrollees accounted for by MH/SA users increases with age, reaching a fifth of
      the 45-64 age group. Across the 10 states, MH/SA spending represents 11% of total
      Medicaid expenditures. When their expenditures for non-MH/SA services are also
      considered, MH/SA users account for 28% of total Medicaid expenditures.

PMID- 11330015
TI  - Self-report of improvement following hospitalization for electroconvulsive
      therapy: relationship to functional status and service use.
AB  - From the perspective of the consumer, improvement is important in the assessment
      of treatment outcome. In order to gain a better understanding of health related
      factors that are meaningful to service recipients, patients who had been
      hospitalized for electroconvulsive therapy were surveyed following discharge to
      the community. Self-reported improvement was related to frequency of social
      contact and being able to engage in useful work. It was also related to a global
      assessment-of-functioning score at the time of discharge from the hospital. The
      receipt of aftercare was not related to the degree of self-reported improvement
      in this study.

PMID- 11330016
TI  - Access to mental health services and health sector social capital.
AB  - Mental health services are underused relative to mental illness rates. We
      hypothesized a positive correlation between use of mental health services and
      community-level health care social capital. Community Tracking Study data from 43
      cities (N = 43,278), merged with the National Profile of Local Health Departments
      and other sources, show that use of mental health services was greater when
      public health districts collaborated with managed care organizations and other
      community groups, independent of individual predictors and health care system
      variables. Use was also positively associated with community levels of public
      insurance coverage and with direct public health provision of behavioral health
      care services. Research is needed to understand the mechanisms by which social
      capital may improve access to mental health services.

PMID- 11330017
TI  - Human resource development: a critical gap in child mental health reform.

PMID- 11330018
TI  - Managed mental health care: a home grown product.

PMID- 11330019
TI  - E-health and HIPAA: important emerging issues affecting our practice.

PMID- 11330020
TI  - Genital herpes in pregnant and nonpregnant women.
AB  - The incidence of genital herpes is increasing. Proper diagnosis and management is
      crucial in pregnant women because transmission to neonates can be deadly. The
      diagnosis and management of potential genital herpes obstetric complications can
      decrease transmission rates to neonates. Standards of care have recently changed
      regarding the clinical presentation of genital herpes: Many cases of genital
      herpes are asymptomatic. This article discusses management and treatment options
      in pregnant and nonpregnant women.

PMID- 11330021
TI  - Managing dog, cat, and human bite wounds.
AB  - Many bite wound patients seek treatment in primary care clinics instead of
      emergency departments. Without treatment, bite wounds can become infected.
      Presenting symptoms are usually wound site pain with cellulitis and purulent
      drainage. The infection originates from the oropharyngeal flora of the biting
      animal or human and the victim's skin. Primary care clinicians must be able to
      assess and manage animal and human bites, initiate antibiotic therapy if
      indicated, and refer patients for surgery or rabies prophylaxis when appropriate.
      Prompt assessment and treatment can prevent most bite wound complications.

PMID- 11330022
TI  - Acute seroconversion of HIV infection in the ambulatory care setting.
AB  - Patients frequently visit ambulatory care settings with acute human
      immunodeficiency virus (HIV) seroconversion illness, but the illness is often
      misdiagnosed. This acute viral syndrome, or seroconversion illness, occurs after
      initial exposure to the HIV virus; it is often resolved before the development of
      HIV-specific antibodies. Primary HIV infection refers to the 12 months following
      infection; it includes an acute time period after exposure when routine HIV
      antibody testing is negative. Primary HIV infection is recognized with the help
      of a detailed screening history. Diagnosis is confirmed through laboratory tests
      that detect virus presence. The accurate diagnosis of primary HIV infection can
      have a beneficial effect on the patient's clinical course and also on public
      health prevention efforts.

PMID- 11330023
TI  - To the rescue!

PMID- 11330024
TI  - The power of yoga.

PMID- 11330025
TI  - Who will live longest?

PMID- 11330026
TI  - Brain games. Alzheimer's gene therapy.

PMID- 11330027
TI  - A license to kill? Critics say a Dutch euthanasia law goes too far.

PMID- 11330028
TI  - The eyes have it.

PMID- 11330029
TI  - Rooting out health care discrimination: it's not just the right thing to do.
AB  - Delivering high-quality health care equally to all patients may be a matter of
      common decency, but unfortunately, it's not always common practice.
      Discrimination in health care can open organizations to serious legal problems
      and cause patient satisfaction scores to plummet. This month's cover article
      details some concrete steps you can take to root out discrimination in your
      organization--whether you know you have a problem or simply suspect you might.

PMID- 11330030
TI  - Study reveals disturbing trends in care of minorities.
AB  - A 2000 survey of Seattle area residents shows that one in five adult residents
      believe they have experienced discrimination in health care. One-sixth of African
      Americans interviewed and nearly a tenth of people of color overall reported
      having faced discrimination in medical care settings in the previous year.

PMID- 11330031
TI  - Do you discriminate? An internal self-assessment tool.
AB  - This self-assessment instrument was developed by Mike Carter, regional manager at
      the Office of Civil Rights (OCR) in New York City, and a variety of health care
      professionals and organizations. It is not a policy guide or enforcement document
      from the OCR, but a road map for your agency or facility.

PMID- 11330032
TI  - Purchasers' group 'leapfrogs' to quality.
AB  - Group hopes purchasing power or members will spark changes. What happens when big
      health care purchasers like AT&T, Boeing, Caterpillar, Delta Airlines, Eli Lilly,
      Ford, General Motors, and IBM get together and voice an opinion about the quality
      of health care? Hospitals listen. At least that's the theory behind the Leapfrog
      Group, an organization sponsored by the Business Roundtable and including some 70
      companies that hope to improve safety in health care by alerting patients to key
      features of hospitals around the country.

PMID- 11330033
TI  - How to spring clean your organization's data.
AB  - It's time for a thorough spring-cleaning of your company's data. Corporate data
      are a lot like someone's closet: packed to the point of bursting; filled with
      items that are similar but not quite identical; archiving things that haven't
      been worn in years; sprinkled with a few items that were trendy but not useful
      over the long term; holding other gems that are worn all the time because they're
      good quality, they work well together, and they fit your lifestyle; and storing
      the indispensable favorite pair of bluejeans. In this month's guest column,
      Connie L. Van Fleet will help you decide what data to keep and what to toss.

PMID- 11330034
TI  - Vaccine safety.

PMID- 11330035
TI  - In silicio search for genes encoding peroxisomal proteins in Saccharomyces
      cerevisiae.
AB  - The biogenesis of peroxisomes involves the synthesis of new proteins that after,
      completion of translation, are targeted to the organelle by virtue of peroxisomal
      targeting signals (PTS). Two types of PTSs have been well characterized for
      import of matrix proteins (PTS1 and PTS2). Induction of the genes encoding these
      matrix proteins takes place in oleate-containing medium and is mediated via an
      oleate response element (ORE) present in the region preceding these genes. The
      authors have searched the yeast genome for OREs preceding open reading frames
      (ORFs), and for ORFs that contain either a PTS1 or PTS2. Of the ORFs containing
      an ORE, as well as either a PTS1 or a PTS2, many were known to encode bona fide
      peroxisomal matrix proteins. In addition, candidate genes were identified as
      encoding putative new peroxisomal proteins. For one case, subcellular location
      studies validated the in silicio prediction. This gene encodes a new peroxisomal
      thioesterase.

PMID- 11330036
TI  - New aspects of sterol carrier protein 2 (nonspecific lipid-transfer protein) in
      fusion proteins and in peroxisomes.
AB  - Sterol carrier protein 2 (SCP2) is a 13-kDa peroxisomal protein, identical to
      nonspecific lipid-transfer protein, and stimulates various steps of cholesterol
      metabolism in vitro. Although the name is reminiscent of acyl carrier protein,
      which is involved in fatty acid synthesis, SCP2 does not bind to lipids
      specifically or stoichiometrically. This protein is expressed either as a small
      precursor or as a large fusion (termed SCPx) that carries at its C-terminal the
      complete sequence of SCP2. SCPx exhibits 3-oxoacyl-CoA thiolase activity, as well
      as sterol-carrier and lipid-transfer activities. The N- and C-terminal parts of
      SCPx are similar to the nematode protein P-44 and the yeast protein PXP-18,
      respectively. P-44, which has no SCP2 sequence, thiolytically cleaved the side
      chain of bile acid intermediate at a rate comparable to that of SCPx. This,
      together with the properties of other fusions with SCP2-like sequence, suggests
      that the SCP2 part of SCPx does not play a direct role in thiolase reaction. PXP
      18, located predominantly inside peroxisomes, is similar to SCP2 in primary
      structure and lipid-transfer activity, and protects peroxisomal acyl-CoA oxidase
      from thermal denaturation. PXP-18 dimerized at a high temperature, formed an
      equimolar complex with the oxidase subunit, and released the active enzyme from
      the complex when the temperature went down. This article attempts to gain insight
      into the role of SCP2, and to present a model in which PXP-18, a member of the
      SCP2 family, functions as a molecular chaperone in peroxisomes.

PMID- 11330037
TI  - Alkyl-dihydroxyacetonephosphate synthase.
AB  - The initial steps of ether phospholipid biosynthesis take place in peroxisomes.
      Alkyl-dihydroxyacetonephosphate synthase, the peroxisomal enzyme that actually
      introduces the ether linkage, has been purified from guinea pig liver in this
      laboratory. With the amino acid sequences obtained from this protein, the authors
      were able to clone the cDNAs encoding this enzyme from both guinea pig and human
      liver. In both cases, the enzyme appears to be synthesized as a precursor protein
      with a N-terminal cleavable presequence containing a peroxisomal targeting signal
      (PTS) type 2. Levels of the enzyme protein were found to be strongly reduced in
      human fibroblasts derived from Zellweger syndrome and rhizomelic chondrodysplasia
      punctata patients. The molecular basis of an isolated alkyl
      dihydroxyacetonephosphate synthase deficiency was resolved. A clone encoding a
      Caenorhabditis elegans homolog of the mammalian enzymes was characterized. In
      contrast to the mammalian enzymes, this C. elegans enzyme lacks a N-terminal PTS
      type 2 motif, but carries a C-terminal PTS type 1.

PMID- 11330038
TI  - Evolution of urate-degrading enzymes in animal peroxisomes.
AB  - The end product of purine metabolism varies from species to species. The
      degradation of purines to urate is common to all animal species, but the
      degradation of urate is much less complete in higher animals. The comparison of
      subcellular distribution, intraperoxisomal localization forms, molecular
      structures, and some other properties of urate-degrading enzymes (urate oxidase,
      allantoinase, and allantoicase) among animals is described. Liver urate oxidase
      (uricase) is located in the peroxisomes in all animals with urate oxidase. On the
      basis of the comparison of intraperoxisomal localization forms, mol wt, and
      solubility of liver urate oxidase among animals, it is suggested that amphibian
      urate oxidase is a transition form in the evolution of aquatic animals to land
      animals. Allantoinase and allantoicase are different proteins in fish liver, but
      the two enzymes form a complex in amphibian liver. The subcellular localization
      of allantoinase and allantoicase varies among fishes. Hepatic allantoinase is
      located both in the peroxisomes and in the cytosol in saltwater fishes, and only
      in the cytosol in freshwater fishes. Hepatic allantoicase is located on the outer
      surface of the peroxisomal membrane in the mackerel group and in the peroxisomal
      matrix in the sardine group. Amphibian hepatic allantoinase-allantoicase complex
      is probably located in the mitochondria. On the basis of previous data, changes
      of allantoinase and allantoicase in molecular structure and intracellular
      localization during animal evolution may be as follows: Fish liver allantoinase
      is a single peptide with a mol wt of 54,000, and is located both in the
      peroxisomes and in the cytosol, or only in the cytosol. Fish liver allantoicase
      consists of two identical subunits with a mol wt of 48,000, and is located in the
      peroxisomal matrix or on the outer surface of the peroxisomal membrane. The
      evolution of fishes to amphibia resulted in the dissociation of allantoicase into
      subunits, and in the association of allantoinase with the subunit of
      allantoicase. This amphibian enzyme was lost by further evolution.

PMID- 11330039
TI  - The 70-kDa peroxisomal membrane protein (PMP70), an ATP-binding cassette
      transporter.
AB  - The 70-kDa peroxisomal membrane protein (PMP70) is one of major components of
      peroxisomal membranes. In rodents, PMP70 is markedly induced by administration of
      hypolipidemic agents in parallel with peroxisome proliferation and the induction
      of peroxisomal fatty acid beta-oxidation enzymes. PMP70 is an ATP-binding
      cassette transporter, identified for the first time in intracellular membranes of
      eukaryotic cells. The authors' recent studies suggest that PMP70 is synthesized
      on free polysomes and posttranslationally inserted into peroxisomal membranes,
      and assembles as dimeric or oligomeric forms on peroxisomal membranes. PMP70 is
      suggested to be involved in metabolic transport of long-chain acyl-CoA across
      peroxisomal membranes.

PMID- 11330040
TI  - Sorting of peroxisomal and mitochondrial carnitine acetyltransferase isozymes in
      the diploid yeast, Candida tropicalis.
AB  - Peroxisomal and mitochondrial carnitine acetyltransferase (CAT; EC 2.3.1.7)
      isozymes are synthesized from the first and second ATG codons of the open reading
      frame of one gene, Candida tropicalis CAT. Primer extension analysis and RNase
      protection assay revealed that the peroxisomal CAT, initiating at the second AUG
      codon of the transcripts, was synthesized by a translational readthrough of the
      first AUG codon of the open reading frame. When C. tropicalis CAT was introduced
      into the other yeast, Saccharomyces cerevisiae, 5' ends of transcripts were
      similar to those observed in C. tropicalis. Peroxisomal and mitochondrial CAT
      isozymes were strongly suggested to occur by the alternative initiation of
      translation, chiefly dependent on the structure or sequence context of the region
      from the 5' end to the second AUG codon; their transcripts harbored sufficient
      information to bring about alternative initiation of translation in both yeasts.
      Sorting of peroxisomal and mitochondrial CAT isozymes to their own compartment
      was carried out by their own targeting sequences, but, before transportation to
      their destination, their biosyntheses were regulated by alternative initiation of
      translation.

PMID- 11330041
TI  - A leaf-peroxisomal protein, hydroxypyruvate reductase, is produced by light
      regulated alternative splicing.
AB  - Hydroxypyruvate reductase (HPR) is localized in leaf peroxisomes in plants, and
      it plays an important role in the glycolate pathway of photorespiration. In this
      laboratory, two highly homologous cDNAs for pumpkin HPR (HPR1 and HPR2) have been
      obtained, and appear to be produced from the same primary transcript by
      alternative splicing. Analyses at the mRNA level showed that the amounts of the
      two HPR mRNAs is changed in response to light, suggesting that light changes the
      splicing pattern of HPR pre-mRNA from almost equal amounts of two HPR mRNAs to
      greater production of HPR2 mRNA. From the sequences of the two HPR cDNAs, the
      HPR1 protein, but not the HPR2 protein, was found to have a targeting sequence
      into peroxisomes at the carboxy terminus. Analyses of transgenic Arabidopsis
      thaliana expressing fusion proteins with green fluorescent protein confirmed the
      different subcellular localizations of the two HPR proteins. These findings
      indicate the presence of light-regulated alternative splicing of HPR pre-mRNA,
      which controls the subcellular localizations of two HPR proteins in pumpkin
      cells.

PMID- 11330042
TI  - Peroxisome biogenesis and molecular defects in peroxisome assembly disorders.
AB  - Peroxisome assembly in mammals requires more than 14 genes. So far, we have
      isolated seven complementation groups (CGs) of peroxisome biogenesis-defective
      Chinese hamster ovary (CHO) cell mutants, Z65, Z24/ZP107, ZP92, ZP105/ZP139,
      ZP109, ZP110, ZP114. Two peroxin cDNAs, PEX2 and PEX6, were first cloned by
      genetic phenotype-complementation assay using Z65 and ZP92, respectively, and
      were shown to be responsible for peroxisome biogenesis disorders (PBD) such as
      Zellweger syndrome, of CG-F (the same as CG-X in U.S.A.) and CG-C (the same as CG
      IV), respectively. Pex2p is a RING zinc finger membrane protein of peroxisomes
      and Pex6p is a member of the AAA ATPase family. We likewise isolated PEX12
      encoding a peroxisomal integral membrane protein in the RING family, by
      functional complementation of ZP109, demonstrating PEX12 to be responsible for CG
      III PBD. We also cloned PEX1 by screening of human liver cDNA library, using
      ZP107. PEX1 mutation was delineated to be the genetic cause of PBD in the most
      highest incidence group, CG-E (the same as CG-I). Moreover, we recently found
      that Pex5p is involved in transport of not only PTS1- but also PTS2-protein,
      distinct from yeast Pex5p, using PEX5-defective ZP105 and ZP139. Thus, CHO cell
      mutants defective in peroxisome biogenesis are indeed shown to be very useful for
      the studies of peroxisome assembly and delineating pathogenic genes in PBD.
      Furthermore, we have isolated novel CGs of CHO mutants, ZP119 and ZP126.

PMID- 11330043
TI  - Temperature sensitivity in peroxisome assembly processes characterizes milder
      forms of peroxisome biogenesis disorders.
AB  - Peroxisome biogenesis disorders (PBDs) contain various clinical phenotypes;
      Zellweger syndrome (ZS), neonatal adrenoleukodystrophy (NALD), and infantile
      Refsum disease (IRD), decreasing in the clinical severity in this order. We found
      that all IRD cell lines and some NALD lines belonging to several different
      complementation groups are temperature-sensitive in peroxisome assembly; that is,
      they lacked catalase-positive peroxisomes at 37 degrees C, but do gain the
      peroxisomes at 30 degrees C. We identified heterozygous mutations E55K/R119Stop
      in the PEX2 gene of an IRD patient of complementation group F. The E55K mutation
      was the direct cause of the temperature-sensitivity because similar phenotypes
      could be transferred to PEX2-defective CHO cells by transfecting the mutant gene.
      Thus, temperature-sensitive peroxisome assembly is representative of milder forms
      of PBDs.

PMID- 11330044
TI  - Primary hyperoxaluria type 1 in Japan.
AB  - Glyoxylate is an immediate precursor of oxalate, but in its metabolism the
      conversion into glycine catalyzed by serine:pyruvate/alanine:glyoxylate
      aminotransferase (SPT/AGT) appears to be the main route. When SPT/AGT is missing
      as in the case of primary hyperoxaluria type 1 (PH1) more glyoxylate is used for
      the oxalate production, resulting in calcium oxalate urolithiasis and finally
      systemic oxalosis. SPT/AGT is a unique enzyme of species-specific dual organelle
      localization; it is located largely in mitochondria in carnivores and entirely in
      peroxisomes in herbivores and man. For herbivores, the peroxisomal localization
      of SPT/AGT is indispensable to avoid massive production of oxalate, probably
      because liver peroxisomes are the main site of glyoxylate production from
      glycolate, and plants contain glycolate much more than animal tissues. Recently,
      we took charge of laboratory examination for 8 cases of primary hyperoxaluria in
      Japan, and felt that symptoms of some of the Japanese PH1 patients are apparently
      milder than those of Western patients. The reason of this is not clear, but from
      the above mentioned seemingly indispensable association of grass-eating with the
      peroxisomal localization of SPT/AGT it may be related, at least in part, to the
      food habit of Japanese, especially that of old generation, that they prefer
      boiled greens rather than frying or raw vegetables.

PMID- 11330045
TI  - Mutational analysis of X-linked adrenoleukodystrophy gene.
AB  - X-linked adrenoleukodystrophy (ALD) is an inherited peroxisomal disorder
      characterized by progressive neurological dysfunction, occasionally associated
      with adrenal insufficiency. The clinical phenotypes of ALD are quite variable,
      and include childhood ALD, adult-onset ALD, adrenomyeloneuropathy, and Addison's
      disease only. Although the causative gene for ALD has been identified, the
      physiological role of the gene product remains to be clarified. Despite many
      mutations having been identified in patients with these clinical phenotypes, the
      genotype-phenotype correlations have not been clarified. The authors investigated
      genotype-phenotype correlations in ALD by analyses on 29 unrelated Japanese
      patients with ALD and by a review of the literature. All the phenotypes were
      associated with mutations leading to protein truncation, as well as those
      resulting in subtle amino acid changes. Furthermore, there were no differences in
      phenotypic expression among the natures of the subtle amino acid changes. All
      these data indicate that no obvious correlations exist between the phenotypes of
      ALD patients and their genotypes, suggesting that other genetic or environmental
      factors may also be involved in determining phenotypic expression in ALD.

PMID- 11330046
TI  - Peroxisome proliferator-activated receptors, coactivators, and downstream
      targets.
AB  - Peroxisomes in liver parenchymal cells proliferate in response to structurally
      diverse nonmutagenic compounds designated as peroxisome proliferators (PP).
      Sustained induction of peroxisome proliferation and peroxisomal fatty acid beta
      oxidation system in rats and mice leads to the development of liver tumors. Two
      mechanistic issues are important for consideration: elucidation of the upstream
      events responsible for the tissue and species specific induction of the
      characteristic pleiotropic responses by PPs; and delineation of the downstream
      events associated with peroxisome proliferation, and their role in the
      development of liver tumors in species that are sensitive to the induction of
      peroxisome proliferation. The induction of peroxisome proliferation is mediated
      by PP-activated receptor alpha (PPAR alpha), a member of a group of transcription
      factors that regulate the expression of genes associated with lipid metabolism
      and adipocyte differentiation. Three isotypes of this family of nuclear
      receptors, namely PPAR alpha, PPAR gamma, and PPAR delta (also called beta), have
      been identified as products of separate genes. Although PPAR alpha is responsible
      for the PP-induced pleiotropic responses, PPAR gamma seems to be involved in
      adipogenesis and differentiation, but the events associated with PPAR gamma do
      not directly involve peroxisomes and peroxisome proliferation. PPARs
      heterodimerize with 9-cis retinoic acid receptor (RXR), and bind to PP response
      element(s) (PPREs) on the target gene promoter to initiate inducible
      transcriptional activity. Tissue and species responses to PPs depend on
      pharmacokinetics, relative abundance of PPAR isotypes, nature of PPRE in the
      upstream regions of target genes, the extent of competition or cross-talk among
      nuclear transcription factors for PPAR heterodimerization partner retinoid X
      receptor and the modulating role of coactivators and corepressors on ligand
      dependent transcription of PPARs. Using PPAR as bait in the yeast two-hybrid
      system, the authors recently cloned mouse steroid receptor coactivator-1 (SRC-1)
      and PPAR-binding protein (PBP), and identified them as PPAR coactivators. Both
      SRC-1 and PBP contain LXXLL signature motifs, considered necessary and sufficient
      for the binding of coactivators to nuclear receptors. A multifaceted approach,
      which includes the identification of additional coactivators that may be
      responsible for cell specific transcriptional activation of PPAR-mediated target
      genes, and generation of genetically modified animals (transgenic and gene
      disrupted), will be necessary to gain more insight into the upstream and
      downstream targets responsible for the induction of early and delayed PP-induced
      pleiotropic responses. In this context, it is important to note that mice
      deficient in fatty acyl-CoA oxidase, the first and rate-limiting enzyme of the
      peroxisomal beta-oxidation system, revealed that this enzyme is indispensable for
      the physiological regulation of PPAR alpha, and the absence of this enzyme leads
      to sustained transcriptional activation of genes regulated by this receptor.

PMID- 11330047
TI  - PPAR-mediated diverse responses in various tissues of mouse.
AB  - Peroxisome proliferator-activated receptors (PPARs) play the essential role in
      transcriptional modulations of the genes involved in lipid metabolism. In vitro
      studies have shown that all the mechanisms of the modulations are similarly
      mediated by PPAR and the response elements through heterodimerization with
      retinoid X receptors (RXRs). However, PPARs mediate the diverse effects induced
      in various tissues of mouse by their activators. First, PPAR alpha also plays an
      obligatory role in the activator-induced transcriptional modulations of various
      genes, some of which are not related to lipid metabolism. Second, responsiveness
      of various genes to several activators varies considerably. Third, some of the
      activator-induced transcriptional activation of several genes is strictly tissue
      specific. Fourth, the time courses of the activator-induced transcriptional
      modulations are diverse. Following brief review of these diverse responses,
      emphasis is laid on the need for studies of these diversely regulated genes to
      understand the species-general and coordinated interplay between PPARs and other
      factors to maintain lipid homeostasis at the body level.

PMID- 11330048
TI  - Peroxisome biogenesis in the yeast Yarrowia lipolytica.
AB  - Extensive peroxisome proliferation during growth on oleic acid, combined with the
      availability of excellent genetic tools, makes the dimorphic yeast, Yarrowia
      lipolytica, a powerful model system to study the molecular mechanisms involved in
      peroxisome biogenesis. A combined genetic, biochemical, and morphological
      approach has revealed that the endoplasmic reticulum (ER) plays an essential role
      in the assembly of functional peroxisomes in this yeast. The trafficking of some
      membrane proteins to the peroxisomes occurs via the ER, results in their
      glycosylation in the ER lumen, does not involve transit through the Golgi, and
      requires the products of the SEC238, SRP54, PEX1, and PEX6 genes. The authors'
      data suggest a model for protein import into peroxisomes via two subpopulations
      of ER-derived vesicles that are distinct from secretory vesicles. A kinetic
      analysis of the trafficking of peroxisomal proteins in vivo has demonstrated that
      membrane and matrix proteins are initially targeted to multiple vesicular
      precursors that represent intermediates in the assembly pathway of peroxisomes.
      The authors have also recently identified a novel cytosolic chaperone, Pex20p,
      that assists in the oligomerization of thiolase in the cytosol and promotes its
      targeting to the peroxisome. These data provide the first evidence that a
      chaperone-assisted folding and oligomerization of thiolase in the cytosol is
      required for the import of this protein into the peroxisomal matrix.

PMID- 11330049
TI  - Relationship between signal transduction and PPAR alpha-regulated genes of lipid
      metabolism in rat hepatic-derived Fao cells.
AB  - The goal of this study was to characterize phosphorylated proteins and to
      evaluate the changes in their phosphorylation level under the influence of a
      peroxisome proliferator (PP) with hypolipidemic activity of the fibrate family.
      The incubation of rat hepatic derived Fao cells with ciprofibrate leads to an
      overphosphorylation of proteins, especially one of 85 kDa, indicating that kinase
      (or phosphatase) activities are modified. Moreover, immunoprecipitation of 32P
      labeled cell lysates shows that the nuclear receptor, PP-activated receptor,
      alpha isoform, can exist in a phosphorylated form, and its phosphorylation is
      increased by ciprofibrate. This study shows that PP acts at different steps of
      cell signaling. These steps can modulate gene expression of enzymes involved in
      fatty acid metabolism and lipid homeostasis, as well as in detoxication
      processes.

PMID- 11330050
TI  - Involvement of hepatocyte growth factor on hepatocarcinogenesis induced by
      peroxisome proliferators.
AB  - Hepatocyte growth factor (HGF) has been known to enhance the growth of normal
      hepatocytes, but also to inhibit the growth of neoplastic cells. This article
      examines the involvement of HGF in the hepatocarcinogenesis caused by peroxisome
      proliferators (PPs). Up to 78 wk after male F-344 rats were orally given (4
      chloro-6-[2,3-xylidino]-2-pyrimidinylthio) acetic acid (Wy-14,643), the
      hepatocarcinomas and (pre)neoplastic nodules in the livers were observed. At that
      time, the content of HGF and the expression of HGF mRNA in the liver tumors were
      significantly decreased. These changes were observed also in the liver of rats
      treated with other PPs, such as dehydroepiandrosterone and di(2
      ethylhexyl)phthalate, but were not observed in tumors induced by genotoxic
      carcinogens (diethylnitrosamine-phenobarbital). In in vivo experiments, the
      formation of preneoplastic lesions and the tumors caused by Wy-14,643
      administration were markedly suppressed by i.v.-injection of HGF in a dose
      dependent manner. In the colony assay using (pre)neoplastic cells from livers of
      Wy-14,643-treated rats, HGF inhibited the colony formation of (pre)neoplastic
      cells in a dose-dependent manner. These findings may indicate that decreases in
      hepatic HGF levels are common and specific events induced by PPs, but not by
      genotoxic carcinogens, and that those changes play an important role in the
      promotion of neoplastic or preneoplastic cell growth induced by PPs.

PMID- 11330051
TI  - Mouse models for peroxisome biogenesis disorders.
AB  - The gene knockout technology has been applied to generate mice lacking functional
      peroxisomes. These mice are a model for Zellweger syndrome and other peroxisome
      biogenesis disorders that are lethal in early life. Extensive biochemical,
      ultrastructural, and neurodevelopmental analyses indicate that the peroxisome
      deficient mice closely mimic the pathology in Zellweger patients and will be a
      very useful tool to elucidate the pathogenesis of this disease.

PMID- 11330052
TI  - Very-long-chain fatty acid metabolism in adrenoleukodystrophy protein-deficient
      mice.
AB  - X-linked adrenoleukodystrophy (X-ALD) is characterized by progressive mental and
      motor deterioration, with demyelination of the central and peripheral nervous
      system. Its principal biochemical abnormality is the accumulation of very-long
      chain fatty acids (VLCFAs) in tissues and body fluids, caused by the impairment
      of peroxisomal beta-oxidation. The authors have generated a line of mice
      deficient in ALD protein (ALDP) by gene targeting. ALDP-deficient mice appeared
      normal clinically, at least up to 12 mo. Western blot analysis showed absence of
      ALDP in the brain, spinal cord, lung, and kidney. The amounts of C26:0 increased
      by 240% in the spinal cord. VLCFA beta-oxidation in cultured hepatocytes was
      reduced to 50% of normal. The authors investigated the roles of ALDP in VLCFA
      beta-oxidation using the ALDP-deficient mice. Very-long-chain acyl-CoA synthetase
      (VLACS) is functionally deficient in ALD cells. The impairment of VLCFA beta
      oxidation in the ALDP-deficient fibroblasts was not corrected by over-expression
      of VLACS only, but was done by co-expression of VLACS and ALDP, suggesting that
      VLACS requires ALDP to function. VLACS was detected in the peroxisomal and
      microsomal fractions of the liver from both types of mice. Peroxisomal VLACS was
      clearly decreased in the ALDP-deficient mouse. Thus, ALDP is involved in the
      peroxisomal localization of VLACS.

PMID- 11330053
TI  - Molecular changes in the D-bifunctional protein cDNA sequence in Australasian
      patients belonging to the bifunctional protein complementation group.
AB  - The cDNA sequence for the human D-bifunctional protein (D-BP: 17 beta
      hydroxysteroid dehydrogenase IV) was investigated in patients with peroxisomal
      disorders belonging to the BP complementation group (CG). In three cases,
      analysis of polymerase chain reaction products generated from the patients' cDNA
      indicated the presence of a deletion within the region corresponding to
      nucleotides 209-537 of the normal cDNA sequence. Subsequent sequencing revealed
      that, in two of the patients, 47 base pairs were missing, with the deletion
      corresponding to nucleotides 302/3-349/50 of the normal sequence. In the third
      patient, a smaller deletion of 22 bp (nucleotides 280/1-302/3) was characterized.
      Only the mutant sequence was detected in each of these cases, consistent with
      parental consanguinity. Both deletions cause a frameshift, and would lead to
      premature termination of the BP. Available family members were also investigated,
      and the findings conformed with expectations for an autosomal recessive disorder.
      In addition to the deletions, a number of other base changes have been identified
      in this series of patients. In particular, one patient, whose parents were also
      consanguineous, was homozygous for a base change, which results in a
      nonconservative substitution of serine 177 with a phenylalanine residue. The
      functional significance of this amino acid substitution, as well as the other
      identified changes, is still to be determined. Nevertheless, our data provide
      strong support for the hypothesis that defects in the gene for the D-BP are
      responsible for the beta-oxidation defect in patients belonging to the BP CG.

PMID- 11330054
TI  - Isolation of peroxisome-defective CHO mutant cells using green fluorescent
      protein.
AB  - The authors constructed a recombinant green fluorescent protein (GFP) (PTS-GFP),
      which carries peroxisome targeting signal (PTS1 or PTS2) as an additional
      sequence, by polymerase chain reaction. The gene encoding for the recombinant GFP
      was constructed into an eukaryotic expression vector, and stable transformant of
      CHO cell expressing PTS-GFP was isolated, following the transfection of the
      plasmid encoding for the GFP. Each expressed PTS-GFP appeared to be localized in
      peroxisomes, because the GFP was observed in cellular structures, as was
      catalase. The observation proposed a visual screening procedure for isolating
      peroxisome-defective mutant. Following an enrichment of mutant cells by use of 9
      (1'-pyrene)nonanol/ultraviolet irradiation (P9OH/UV) method, five peroxisome
      defective mutants were isolated by pursuing the fluorescent signals from GFP. Two
      mutants (SK24 and SK32) were isolated from CHO cells expressing PTS1-GFP, and
      three mutants (PT13, PT32, and PT54) were isolated from cells expressing PTS2
      GFP. Four mutants, except for PT13, showed cytosolic distributions of both PTS
      GFP and catalase. On the other hand, mutant PT13 showed a cytosolic distribution
      on PTS2-GFP, but a peroxisomal distribution on catalase. Cell fusion analysis
      between SK24 mutant and other mutants indicated that PT54 mutant is in the same
      complementation group (CG) as SK24, but that SK32, PT13, and PT32 mutants are in
      different complementation group(s) from SK24.

PMID- 11330055
TI  - Peroxisomal proteins in rat gametes.
AB  - Peroxisomes are essential subcellular organelles, which appear to be derived from
      pre-existing organelles. This biogenetic mechanism assumes the presence of
      peroxisomes in either or both mammalian gametes (sperms and/or oocytes). In order
      to test the presence and subcellular localization of peroxisomal proteins in rat
      sperms and oocytes, the authors carried out fractionation and immunofluorescence
      experiments. The results showed that rat oocytes contain peroxisome-like
      structures, which were detected by indirect immunofluorescence, using an antisera
      against total peroxisomal proteins. In contrast, such structures were not
      detected in rat sperms, which appear to contain catalase localized in the cell
      cytosol. The results reported herein show evidence for the first time of the
      presence of peroxisome-like structures in mammalian oocytes, and provide evidence
      for the peroxisome biogenesis hypothesis, by division of pre-existing organelles.

PMID- 11330056
TI  - Transport of peroxisomal proteins synthesized as large precursors in plants.
AB  - Plant peroxisomes contain at least four proteins, namely, citrate synthase,
      malate dehydrogenase, long-chain acyl-CoA oxidase, and 3-ketoacyl-CoA thiolase,
      which are synthesized as large precursors with an N-terminal cleavable
      presequence. Each presequence has a conserved domain (R[I/L/Q]-X5-HL) that is
      homologous to peroxisomal targeting signal 2 from mammals and yeasts. In
      addition, a cysteine residue is found at the C-terminal ends of the presequences,
      whose function has not yet been described. The authors analyzed the function of
      the presequences and the conserved amino acids using transgenic Arabidopsis
      plants, which accumulate beta-glucuronidase carrying the presequence of the
      peroxisomal proteins from plants. Immunological and immunocytochemical studies on
      the transgenic plants showed that a conserved sequence in the extrapeptides is
      essential for targeting to peroxisomes, and a cysteine residue at the cleavage
      site is involved in the processing of the presequence. These results suggest that
      the presequences of the peroxisomal proteins function as targeting signals, and
      are necessary for the recognition of the processing.

PMID- 11330057
TI  - ARF- and coatomer-mediated peroxisomal vesiculation.
AB  - The authors characterized on a molecular level the clofibrate-inducible 26-kDa
      integral peroxisomal membrane protein (Pmp26p, Pex11-1p) of rat liver. By
      screening cDNA databases with the obtained Pex11-1p-cDNA, a second homologous
      cDNA was identified that codes for a polypeptide with slightly larger molecular
      mass than Pex11-1p. The authors call this polypeptide Pex11-2p. Studies on the
      topology of Pex11-1p revealed two transmembrane domains with the N- and C
      terminus facing the cytoplasm. The C-terminal tail of Pex11-1p ends in a
      consensus dilysine motif of the type -KXKXX-COOH, which is known to be involved
      in the ADP-ribosylation factor (ARF)1-coat protein (COP) I coat (ARF)1-dependent
      membrane recruitment to Golgi membranes. Studies with isolated peroxisomes
      incubated in the presence of cytosol, adenosine triphosphate and GTP gamma S,
      indeed, provided evidence for specific binding of ARF and coatomer to
      peroxisomes. Expression of Pex11-1p in Chinese hamster ovary (CHO) wild-type
      cells led to a twofold increase in the number of peroxisomes, but expression in a
      temperature-sensitive CHO mutant, defective in coatomer, induced elongation and
      tubulation of peroxisomal structures, rather than numerical proliferation. The
      obtained results for the first time offer a mechanism explaining Pex11-1p-, as
      well as ARF- and coatomer-mediated peroxisomal vesiculation. Two models are
      presented that may explain how these observations fit in with peroxisome
      biogenesis.

PMID- 11330058
TI  - Peroxisomal and mitochondrial targeting of serine:pyruvate/alanine:glyoxylate
      aminotransferase in rat liver.
AB  - Serine:pyruvate/alanine:glyoxylate aminotransferase (SPT or SPT/AGT) of rat liver
      is a unique enzyme of dual subcellular localization, and exists in both
      mitochondria and peroxisomes. To characterize a peroxisomal targeting signal of
      rat liver SPT, a number of C-terminal mutants were constructed and their
      subcellular localization in transfected COS-1 cells was examined. Deletion of C
      terminal NKL, and point mutation of K2 (the second Lys from the C-terminus), K4
      and E15 caused accumulation of translated products in the cytoplasm. This
      suggests that the PTS of SPT is not identical to PTS1 (the C-terminal SKL motif)
      in that it is not restricted to the C-terminal tripeptide. In vitro synthesized
      precursor for mitochondrial SPT was highly sensitive to the proteinase K
      digestion, whereas peroxisomal SPT (SPTp) was fairly resistant to the protease.
      In in vitro import experiment with purified peroxisomes, however, SPTp recovered
      in the peroxisomal fraction was very sensitive to the protease. These results
      suggest that the mitochondrial precursor is synthesized as an unfolded form and
      is translocated into the mitochondrial matrix, whereas SPTp is synthesized as a
      folded form and its conformation changes to an unfolded form just before
      translocation into peroxisomes.

PMID- 11330059
TI  - Hansenula polymorpha Pex14p phosphorylated in vivo.
AB  - Hansenula polymorpha Pex14p is a novel peroxisomal membrane protein essential for
      peroxisome biogenesis. In vivo labeling experiment of wild-type cells with 32P
      orthophosphate and alkaline phosphatase treatment of labeled Pex14p indicate that
      Pex14p is phosphorylated in vivo. Analysis of the phosphoamino acid in the
      phosphorylated Pex14p suggested that the major phosphoamino acid was acid labile.
      Using expression system of several truncated Pex14ps in a PEX14-deletion strain
      it is suggested that the phosphorylation site of Pex14p resides in the C-terminal
      58 residues.

PMID- 11330060
TI  - Genetic evaluation of peroxisomal and cytosolic acetoacetyl-CoA thiolase isozymes
      in n-alkane-assimilating diploid yeast, Candida tropicalis.
AB  - The n-alkane-assimilating diploid yeast, Candida tropicalis, possesses two
      acetoacetyl-CoA thiolase (Thiolase I) isozymes encoded by one allele: peroxisomal
      and cytosolic Thiolase Is encoded by both CT-T1A and CT-T1B. To clarify the
      function of peroxisomal and cytosolic Thiolase Is, the site-directed mutation
      leading Thiolase I delta C6 without a putative C-terminal peroxisomal targeting
      signal was introduced on CT-T1A locus in the ct-t1b delta-null mutant. The C
      terminus-truncated Thiolase I was active and solely present in the cytosol.
      Although the ct-t1a delta/t1b delta-null mutants showed mevalonate auxotrophy,
      the mutants having the C-terminus-truncated Thiolase I did not require mevalonate
      for growth, as did the strains having cytosolic Thiolase I. These results
      demonstrate that the presence of Thiolase I in the cytoplasm is indispensable for
      the sterol synthesis in this yeast. It is of greater interest that peroxisomal
      and cytosolic Thiolase I isozymes, products of the same genes, play different
      roles in the respective compartments, although further investigations will be
      necessary to analyze how to be sorted into peroxisomes and the cytosol.

PMID- 11330061
TI  - Metabolic significance and expression of Caenorhabditis elegans type II 3-oxoacyl
      CoA thiolase.
AB  - The authors cloned the cDNA of the nematode Caenorhabditis elegans encoding a 44
      kDa protein (P-44), which is similar to sterol carrier protein x (SCPx). Genomic
      DNA data and Northern blot analysis excluded the possibility of P-44 forming SCPx
      like fusion protein. P-44 is required in the formation of bile acid in vitro from
      CoA esters of their enoyl-form intermediate in the presence of D-3-hydroxyacyl
      CoA dehydratase/D-3-dehydrogenase bifunctional protein. Also, rat SCPx converts
      24-hydroxy-form intermediate to bile acid under similar conditions. From this and
      other evidence, P-44 and SCPx were categorized as type II thiolase. The mRNA
      encoding P-44 was detected in every developmental stage of C. elegans: egg,
      larval stages, and adult. P-44, therefore, seems essential for the normal
      functioning of this organism.

PMID- 11330062
TI  - Functional transformation of plant peroxisomes.
AB  - Peroxisomes in higher plant cells are known to differentiate into at least three
      different classes, namely, glyoxysomes, leaf peroxisomes, and unspecialized
      peroxisomes, depending on the cell types. In germinating fatty seedlings,
      glyoxysomes that first appear in the etiolated cotyledonary cells are
      functionally transformed into leaf peroxisomes during greening. Subsequently, the
      organelles are transformed back into glyoxysomes during senescence of the
      cotyledons. Flexibility of function is a distinct feature of plant peroxisomes.
      This article briefly describes recent studies of the regulatory mechanisms
      involved in the changes of the function of plant peroxisomes.

PMID- 11330063
TI  - Peroxisomes in permanent and provisional kidneys. Phylogenic and ontogenic
      considerations.
AB  - Peroxisomes in three forms of vertebrate kidney (pronephros, mesonephros, and
      metanephros), as permanent or provisional kidney, are summarized concerning their
      ultrastructure and developmental changes. Because the peroxisome is known to be
      diverse in mammalian metanephros, and species difference is its distinctive
      feature among cell organelles, information should be obtained on each kidney of
      each species. The ultrastructural and biochemical features of peroxisomes have at
      least been partly delineated in the metanephros and mesonephros, but nothing is
      known about the pronephros. Ultrastructural studies of the metanephric
      peroxisomes are present in mammals, birds, and reptiles, but information on their
      development is restricted to mammals and birds. As for the mesonephric
      peroxisomes, both ultrastructural and developmental data have been accumulating
      on mammals and amphibians, and ultrastructural information is present on fishes,
      but not on birds and reptiles. At present, studies on peroxisomes of provisional
      kidney have been restricted to mammalian mesonephros. The common features of
      renal peroxisomes previously examined are that they are spherical cell organelles
      with a single limiting membrane in ultrastructure, and are positive for catalase.
      Information on the ultrastructure and enzymes is not sufficient at present for
      comparing the ontogenesis of renal peroxisomes with their phylogenesis.

PMID- 11330064
TI  - The human L-pipecolic acid oxidase is similar to bacterial monomeric sarcosine
      oxidases rather than D-amino acid oxidases.
AB  - L-Pipecolic acid oxidase activity is deficient in patients with peroxisome
      biogenesis disorders (PBDs). Because its role, if any, in these disorders is
      unknown, the authors cloned the human gene to order to further study its
      functions. BLAST search of the translated sequence showed greatest homology to
      Bacillus sp. NS-129 monomeric sarcosine oxidase. The purified enzyme could use
      either L-pipecolic acid or sarcosine as a substrate. No homology was found to the
      peroxisomal D-amino acid oxidases. A further comparison of L-pipecolic acid
      oxidase to the two D-amino acid oxidases in peroxisomes showed that the proteins
      differed in many ways. First, both D-amino acid oxidase and L-pipecolic acid
      oxidase showed no enzyme activity in liver from Zellweger syndrome patients; D
      aspartate oxidase activity was unchanged from control levels. Although all were
      targeted to peroxisomes, their targeting signals differed. No L-pipecolic acid
      oxidase was found in brain or other tissues outside of liver and kidney. The D
      amino acid oxidases were similarly and more widely distributed. Finally, although
      D-amino acid degradation is limited to peroxisomes in mammals, L-pipecolic acid
      can be oxidized in either mitochondria or peroxisomes, or both.

PMID- 11330065
TI  - Acyl-CoA thioesterases belong to a novel gene family of peroxisome proliferator
      regulated enzymes involved in lipid metabolism.
AB  - Acyl-CoA thioesterases hydrolyze acyl-CoAs to the corresponding free fatty acid
      plus coenzyme A. The activity is strongly induced in rat and mouse liver after
      feeding the animals peroxisome proliferators (PPs). To elucidate the role of
      these enzymes in lipid metabolism, the authors have cloned the cDNAs
      corresponding to the inducible cytosolic and mitochondrial type I enzymes (CTE-I
      and MTE-I), and studied tissue expression and nutritional regulation of
      expression of the mRNAs in mice. The constitutive expression of both mRNAs was
      low in liver, with CTE-I expressed mainly in kidney and brown adipose tissue, and
      MTE-I expressed in brown adipose tissue and heart. As expected, the expression in
      liver of both the CTE-I and MTE-I mRNAs were strongly induced (> 50-fold) by
      treatment with clofibrate. A similar level of induction was observed by fasting
      and a time-course study showed that the CTE-I and MTE-I mRNAs were increased
      already at 6 h after removal of the diet. Refeeding normal chow diet to mice
      fasted for 24 h normalized the mRNA levels with a T1/2 of about 3-4 h. Feeding
      mice a fat-free diet further decreased the expression, possibly indicating
      repression of expression. The strong expression of MTE-I and CTE-I in the heart
      was increased about 10-fold by fasting. To further characterize these highly
      regulated enzymes, the authors have cloned the corresponding genes and promoter
      regions. The structures of the two genes were found to be very similar,
      consisting of three exons and two introns. Exon-intron borders conform to general
      consensus sequences, and, especially, the first exon appears to be highly
      conserved. The promoter regions of both the CTE-I and MTE-I genes contain
      putative PP response elements, suggesting an involvement of PP-activated
      receptors in the regulation of these genes.

PMID- 11330066
TI  - Phosphorylation of 13 kDa nuclear protein in hepatocarcinomas induced by
      peroxisome proliferators.
AB  - Peroxisome proliferators (PPs) are nongenotoxic compounds causing the emergence
      of hepatocellular carcinoma in rodents, but the mechanisms of the
      hepatocarcinogenesis have been unclear. The authors examined the changes in
      phosphorylation of nuclear proteins after treatment with (4-chloro-6-[2,3
      xylidino]-2-pyrimidinylthio) acetic acid (Wy-14,643). Wy-14,643 (0.1% w/w in
      diet) was given orally to male F-344 rats for up to 80 wk. In the
      hepatocarcinomas induced by Wy-14,643, phosphorylation of 13 kDa nuclear protein
      (NP 13), which was resistant to alkaline treatment, was significantly increased.
      NP 13 phosphorylation gradually increased, dependent on treatment period.
      Furthermore, in the hepatocarcinomas induced by other PP, di(2
      ethylhexyl)phthalate, increase in NP13-phosphorylation was also observed.
      Therefore, NP 13-phosphorylation may relate to development of preneoplastic or
      neoplastic lesions induced by PPs.

PMID- 11330067
TI  - Peroxisomal proliferation induced by treatment with clofibrate in a patient with
      a peroxisomal disease.
AB  - The induction of peroxisomal proliferation in liver parenchymal cells of rats fed
      a diet containing clofibrate, a hypolipidemic drug, is a well-established event.
      However, the available data on human hepatocytes in vivo and in vitro indicate
      that agents that induce peroxisomal proliferation in rats and mice have no effect
      on human liver cells. The authors are reporting the case of a patient with
      clinical and laboratory diagnosis of X-linked-adrenoleukodystrophy. In an initial
      liver biopsy, a reduced volume fraction of peroxisomes was found (Vv. = .012)
      after a morphometric analysis, initiating treatment with clofibrate at a dose of
      1.5 g/d. The administration of clofibrate was maintained for 7 yr. Liver biopsies
      were taken after 2, 4, and 7 yr, to follow the peroxisomal response. Results
      demonstrated a 500% increase in peroxisomal Vv. (.060) after 2 yr of treatment,
      compared with the pretreatment Vv. In subsequent biopsies, the peroxisomal Vv.
      value was maintained at 225 and 183% increases above the pretreatment biopsy
      (.027 and .022, respectively).

PMID- 11330068
TI  - Disruption of a yeast very-long-chain acyl-CoA synthetase gene simulates the
      cellular phenotype of X-linked adrenoleukodystrophy.
AB  - X-linked adrenoleukodystrophy (X-ALD) is characterized biochemically by elevated
      levels of saturated very long-chain fatty acids (VLCFAs) in plasma and tissues.
      In X-ALD, peroxisomal very-long-chain acyl-CoA synthetase (VLCS) fails to
      activate VLCFAs, preventing their degradation via beta-oxidation. However, the
      product of the defective XALD gene (ALDP) is not a VLCS, but rather a peroxisomal
      membrane protein (PMP). Disruption of either or both of two yeast PMP genes
      related to the XALD gene did not produce a biochemical phenotype resembling that
      found in X-ALD fibroblasts. The authors identified a candidate yeast VLCS gene
      (the FAT1 locus) by its homology to rat liver VLCS. Disruption of this gene
      decreased VLCS activity, but had no effect on long-chain acyl-CoA synthetase
      activity. In FAT1-disruption strains, VLCS activity was reduced to 30-40% of wild
      type in both a microsome-rich 27,000 g supernatant fraction and a peroxisome- and
      mitochondria-rich pellet fraction of yeast spheroplast homogenates. Separation of
      the latter organelles by density gradient centrifugation revealed that VLCS
      activity was peroxisomal and not mitochondrial. VLCS gene-disruption strains had
      increased cellular VLCFA levels, compared to wild-type yeast. The extent of both
      the decrease in peroxisomal VLCS activity and the VLCFA accumulation in this
      yeast model resembles that observed in cells from X-ALD patients.
      Characterization of the gene(s) responsible for the residual peroxisomal VLCS
      activity may suggest new therapeutic approaches in X-ALD.

PMID- 11330069
TI  - Three-dimensional ultrastructural analysis of peroxisomes in HepG2 cells. Absence
      of peroxisomal reticulum but evidence of close spatial association with the
      endoplasmic reticulum.
AB  - Peroxisomes in the human hepatoblastoma cell line, HepG2, exhibit distinct
      alterations of shape, size, and distribution, dependent on culture conditions
      (cell density, duration in culture, and presence of specific growth factors).
      Although many cells with elongated tubular peroxisomes are present in thinly
      seeded cultures, spherical particles forming large focal clusters are found in
      confluent cultures. The authors have analyzed the ultrastructure and the spatial
      relationship of peroxisomes of HepG2 cells at different stages of
      differentiation, using three-dimensional (3D)-reconstruction of ultrathin serial
      sections, and electronic image processing. Cells were prepared for
      immunofluorescence using different antibodies against peroxisomal matrix and
      membrane proteins, as well as for electron microscopy after the alkaline 3,3'
      diaminobenzidine staining for catalase. The results indicate that the tubular
      peroxisomes, which can reach a length of several microns, are consistently
      isolated, and never form an interconnected peroxisomal reticulum. At the time of
      disappearance of tubular peroxisomes, rows of spherical peroxisomes, arranged
      like beads on a string, are observed, suggesting fission of tubular ones. In
      differentiated confluent cultures, clusters of several peroxisomes are seen,
      which, by immunofluorescence, appear as large aggregates, but after 3D
      reconstruction consist of single spherical and angular peroxisomes without
      interconnections. The majority of such mature spherical peroxisomes (but not the
      tubular ones) exhibit tail-like, small tubular and vesicular attachments to their
      surface, suggesting a close functional interaction with neighboring organelles,
      particularly the endoplasmic reticulum, which is often observed in close vicinity
      of such peroxisomes.

PMID- 11330070
TI  - Environmental response of yeast peroxisomes. Aspects of organelle assembly and
      degradation.
AB  - Nutritional changes can affect either the assembly or disassembly of yeast
      peroxisomes. In the past decade, insights regarding the molecular mechanisms of
      peroxisome assembly have been gained chiefly through the cloning of the PEX genes
      obtained by complementation of corresponding pex mutants in several yeast strains
      and Chinese hamster ovary cell lines. Depletion of these peroxins (proteins
      encoded by PEX genes) by deletion of the corresponding genes affects peroxisomal
      protein import, biogenesis, or proliferation. To complement these studies in the
      field, the authors undertook an investigation of the functions of a subset of
      Candida boidinii peroxisomal membrane proteins (PMPs), Pex11, Pmp47, and Pmp20,
      by analyzing strains of C. boidinii in which the genes encoding these proteins
      were deleted. The authors' studies show that Pex11p is involved in peroxisome
      proliferation; Pmp47 plays a role in the translocation, folding, or assembly of
      dihydroxyacetone synthase; and Pmp20 is probably involved in methanol metabolism.
      In contrast to the studies on peroxisome assembly, the molecular mechanisms of
      peroxisome degradation remain poorly understood. To shed light on this problem,
      the authors isolated Pichia pastoris mutants defective in peroxisome autophagy
      (pag mutants). A novel, double-fluorescence method used for the characterization
      of wild-type cells and of pag mutants enabled us to dissect the microautophagic
      degradation of peroxisomes into several distinct stages. These studies show that
      specific PAG gene products are involved in multiple steps of the process. Future
      cloning and characterization of the functions of PAG genes will reveal the
      molecular basis of peroxisome degradation.

PMID- 11330071
TI  - Peroxisomal beta-oxidation enzymes.
AB  - Peroxisomal fatty acid oxidation enzymes are summarized in comparison to their
      mitochondrial counterparts. The peroxisomal enzymes involved in the beta
      oxidation spiral are schematically classified into two groups. The first group
      consists of hitherto purified and characterized classical enzymes: palmitoyl-CoA
      oxidase, the L-bifunctional protein, and 3-ketoacyl-CoA. These enzymes are
      inducible and act on the straight chain substrates. The second group consists of
      recently identified enzymes, branched-chain oxidase, the D-bifunctional protein,
      and sterol-carrier protein x, which catalyze four reactions of beta-oxidation
      cycle. These are noninducible and act on branched-chain substrates.

PMID- 11330072
TI  - Peroxisomal lipid degradation via beta- and alpha-oxidation in mammals.
AB  - Peroxisomal beta-oxidation is involved in the degradation of long chain and very
      long chain fatty acyl-(coenzyme A)CoAs, long chain dicarboxylyl-CoAs, the CoA
      esters of eicosanoids, 2-methyl-branched fatty acyl-CoAs (e.g. pristanoyl-CoA),
      and the CoA esters of the bile acid intermediates di- and trihydroxycoprostanic
      acids (side chain of cholesterol). In the rat, straight chain acyl-CoAs
      (including the CoA esters of dicarboxylic fatty acids and eicosanoids) are beta
      oxidized via palmitoyl-CoA oxidase, multifunctional protein-1 (which displays 2
      enoyl-CoA hydratase and L-3-hydroxyacyl-CoA dehydrogenase activities) and
      peroxisomal thiolase. 2-Methyl-branched acyl-CoAs are degraded via pristanoyl-CoA
      oxidase, multifunctional protein-2 (MFP-2) (which displays 2-enoyl-CoA hydratase
      and D-3-hydroxyacyl-CoA dehydrogenase activities) and sterol carrier protein-X
      (SCPX; displaying 2-methyl-3-oxoacyl-CoA thiolase activity). The side chain of
      the bile acid intermediates is shortened via one cycle of beta-oxidation
      catalyzed by trihydroxycoprostanoyl-CoA oxidase, MFP-2 and SCPX. In the human,
      straight chain acyl-CoAs are oxidized via palmitoyl-CoA oxidase, multifunctional
      protein-1, and peroxisomal thiolase, as is the case in the rat. The CoA esters of
      2-methyl-branched acyl-CoAs and the bile acid intermediates, which also possess a
      2-methyl substitution in their side chain, are shortened via branched chain acyl
      CoA oxidase (which is the human homolog of trihydroxycoprostanoyl-CoA oxidase),
      multifunctional protein-2, and SCPX. The rat and the human enzymes have been
      purified, cloned, and kinetically and stereochemically characterized. 3-Methyl
      branched fatty acids such as phytanic acid are not directly beta-oxidizable
      because of the position of the methyl-branch. They are first shortened by one
      carbon atom through the a-oxidation process to a 2-methyl-branched fatty acid
      (pristanic acid in the case of phytanic acid), which is then degraded via
      peroxisomal beta-oxidation. In the human and the rat, alpha-oxidation is
      catalyzed by an acyl-CoA synthetase (producing a 3-methylacyl-CoA), a 3
      methylacyl-CoA 2-hydroxylase (resulting in a 2-hydroxy-3-methylacyl-CoA), and a 2
      hydroxy-3-methylacyl-CoA lyase that cleaves the 2-hydroxy-3-methylacyl-CoA into a
      2-methyl-branched fatty aldehyde and formyl-CoA. The fatty aldehyde is
      dehydrogenated by an aldehyde dehydrogenase to a 2-methyl-branched fatty acid
      while formyl-CoA is hydrolyzed to formate, which is then converted to CO2. The
      activation, hydroxylation and cleavage reactions, and the hydrolysis of formyl
      CoA are performed by peroxisomal enzymes; the aldehyde dehydrogenation remains to
      be localized whereas the conversion of formate to CO2 occurs mainly in the
      cytosol.

PMID- 11330073
TI  - Peroxisomes, lipid metabolism, and human disease.
AB  - In the past few years, much has been learned about the metabolic functions of
      peroxisomes. These studies have shown that peroxisomes play a major role in lipid
      metabolism, including fatty acid beta-oxidation, etherphospholipid biosynthesis,
      and phytanic acid alpha-oxidation. This article describes the current state of
      knowledge concerning the role of peroxisomes in these processes, especially in
      relation to various peroxisomal disorders in which there is an impairment in
      peroxisomal lipid metabolism.

PMID- 11330074
TI  - Peroxisomal matrix protein import. Suppression of protein import defects in
      Hansenula polymorpha pex mutants by overproduction of the PTS1 receptor Pex5p.
AB  - In the past decade, much progress has been made in understanding the mechanisms
      that govern sorting of proteins to the peroxisomal lumen. This article summarizes
      the principal features of how peroxisomal matrix enzymes are thought to reach the
      peroxisome. In addition, it describes recent data that indicate that, in specific
      pex mutants of the methylotrophic yeast Hansenula polymorpha, defects in matrix
      protein import can be (partly) rescued by overproduction of the receptor
      essential for import of these proteins. The implication of these results on the
      mechanisms of matrix protein import is discussed.

PMID- 11330075
TI  - Determination and theoretical aspects of the equilibrium between dissolved
      organic matter and hydrophobic organic micropollutants in water (Kdoc).
AB  - Literature on the equilibrium constant for distribution between dissolved organic
      carbon (DOC) (Kdoc) data of strongly hydrophobic organic contaminants were
      collected and critically analyzed. About 900 Kdoc entries for experimental values
      were retrieved and tabulated, including those factors that can influence them. In
      addition, quantitative structure-activity relationship (QSAR) prediction
      equations were retrieved and tabulated. Whether a partition or association
      process between the contaminant and DOC takes place could not be fully
      established, but indications toward an association process are strong in several
      cases. Equilibrium between a contaminant and DOC in solution was shown to be
      achieved within a minute. When the equilibrium shifts in time, this was caused by
      either a physical or chemical change of the DOC, affecting the lighter fractions
      most. Adsorption isotherms turned out to be linear in the contaminant
      concentration for the relevant DOC concentration up to 100 mg of C/L. Eighteen
      experimental methods have been developed for the determination of the pertinent
      distribution constant. Experimental Kdoc values revealed the expected high
      correlation with partition coefficients over n-octanol and water (Kow) for all
      experimental methods, except for the HPLC and apparent solubility (AS) method.
      Only fluorescence quenching (FQ) and solid-phase microextraction (SPME) methods
      could quantify fast equilibration. Only 21% of the experimental values had a 95%
      confidence interval, which was statistically significantly different from zero.
      Variation in Kdoc values was shown to be high, caused mainly by the large
      variation of DOC in water samples. Even DOC from one sample gave different
      equilibrium constants for different DOC fractions. Measured Kdoc values should,
      therefore, be regarded as average values. Kdoc was shown to increase on
      increasing molecular mass, indicating that the molecular mass distribution is a
      proper normalization function for the average Kdoc at the current state of
      knowledge. The weakly bound fraction could easily be desorbed when other
      adsorbing media, such as a SepPak column or living organism, are present. The
      amount that moves from the DOC to the other medium will depend, among other
      reasons, on the size of the labile DOC fraction and the equilibrium constant of
      the other medium. Variation of Kdoc with temperature turned out to be small,
      probably caused by a small enthalpy of transfer from water to DOC. Ionic strength
      turned out to be more important, leading to changes of a factor of 2-5. The
      direction of this effect depends on the type of ion. With respect to QSAR
      relationships between Kdoc and macroscopic or molecular descriptors, it was
      concluded that only a small number of equations are available in the literature,
      for apolar compounds only, and with poor statistics and predictive power.
      Therefore, a first requirement is the improvement of the availability and quality
      of experimental data. Along with this, theoretical (mechanistic) models for the
      relationship between DOC plus contaminant descriptors on the one side and Kdoc on
      the other should be further developed. Correlations between Kdoc and Kow and
      those between the soil-water partition constant (Koc) and Kow were significantly
      different only in the case of natural aquatic DOC, pointing at substantial
      differences between these two types of organic material and at a high
      correspondence for other types of commercial and natural DOC.

PMID- 11330076
TI  - Biodegradation kinetics for pesticide exposure assessment.
AB  - Understanding pesticide risks requires characterizing pesticide exposure within
      the environment in a manner that can be broadly generalized across widely varied
      conditions of use. The coupled processes of sorption and soil degradation are
      especially important for understanding the potential environmental exposure of
      pesticides. The data obtained from degradation studies are inherently variable
      and, when limited in extent, lend uncertainty to exposure characterization and
      risk assessment. Pesticide decline in soils reflects dynamically coupled
      processes of sorption and degradation that add complexity to the treatment of
      soil biodegradation data from a kinetic perspective. Additional complexity arises
      from study design limitations that may not fully account for the decline in
      microbial activity of test systems, or that may be inadequate for considerations
      of all potential dissipation routes for a given pesticide. Accordingly, kinetic
      treatment of data must accommodate a variety of differing approaches starting
      with very simple assumptions as to reaction dynamics and extending to more
      involved treatments if warranted by the available experimental data. Selection of
      the appropriate kinetic model to describe pesticide degradation should rely on
      statistical evaluation of the data fit to ensure that the models used are not
      overparameterized. Recognizing the effects of experimental conditions and methods
      for kinetic treatment of degradation data is critical for making appropriate
      comparisons among pesticide biodegradation data sets. Assessment of variability
      in soil half-life among soils is uncertain because for many pesticides the data
      on soil degradation rate are limited to one or two soils. Reasonable upper-bound
      estimates of soil half-life are necessary in risk assessment so that estimated
      environmental concentrations can be developed from exposure models. Thus, an
      understanding of the variable and uncertain distribution of soil half-lives in
      the environment is necessary to estimate bounding values. Statistical evaluation
      of measures of central tendency for multisoil kinetic studies shows that
      geometric means better represent the distribution in soil half-lives than do the
      arithmetic or harmonic means. Estimates of upper-bound soil half-life values
      based on the upper 90% confidence bound on the geometric mean tend to accurately
      represent the upper bound when pesticide degradation rate is biologically driven
      but appear to overestimate the upper bound when there is extensive coupling of
      biodegradation with sorptive processes. The limited data available comparing
      distribution in pesticide soil half-lives between multisoil laboratory studies
      and multilocation field studies suggest that the probability density functions
      are similar. Thus, upper-bound estimates of pesticide half-life determined from
      laboratory studies conservatively represent pesticide biodegradation in the field
      environment for the purposes of exposure and risk assessment. International
      guidelines and approaches used for interpretations of soil biodegradation reflect
      many common elements, but differ in how the source and nature of variability in
      soil kinetic data are considered. Harmonization of approaches for the use of soil
      biodegradation data will improve the interpretative power of these data for the
      purposes of exposure and risk assessment.

PMID- 11330077
TI  - Pharmacokinetics, metabolism, and carcinogenicity of arsenic.
AB  - The carcinogenicity of arsenic in humans has been unambiguously demonstrated in a
      variety of epidemiological studies encompassing geographically diverse study
      populations and multiple exposure scenarios. Despite the abundance of human data,
      our knowledge of the mechanism(s) responsible for the carcinogenic effects of
      arsenic remains incomplete. A deeper understanding of these mechanisms is highly
      dependent on the development of appropriate experimental models, both in vitro
      and in vivo, for future mechanistic investigations. Suitable in vitro models
      would facilitate further investigation of the critical chemical species
      (arsenate/arsenite/MMA/DMA) involved in the carcinogenic process, as well as the
      evaluation of the generation and role of ROS. Mechanisms underlying the
      clastogenic effects of arsenic, its role in modulating DNA methylation, and the
      phenomenon of inducible tolerance could all be more completely investigated using
      in vitro models. The mechanisms involved in arsenic's inhibition of ubiquitin
      mediated proteolysis demand further attention, particularly with respect to its
      effects on cell proliferation and DNA repair. Exploration of the mechanisms
      responsible for the protective or anticarcinogenic effects of arsenic could also
      enhance our understanding of the cellular and molecular interactions that
      influence its carcinogenicity. In addition, appropriate in vivo models must be
      developed that consider the action of arsenic as a promoter and/or progressor. In
      vivo models that allow further investigation of the comutagenic effects of
      arsenic are also especially necessary. Such models may employ initiation
      promotion-progression bioassays or transgenic animals. Both in vitro and in vivo
      models have the potential to greatly enhance our current understanding of the
      cellular and molecular interactions of arsenic and its metabolites in target
      tissues. However, refinement of our knowledge of the mechanistic aspects of
      arsenic carcinogenicity is not alone sufficient; an understanding of the
      pharmacokinetics and target tissue doses of the critical chemical species is
      essential. Additionally, a more thorough characterization of species differences
      in the tissue kinetics of arsenic and its methylated metabolites would facilitate
      the development of more accurate and relevant PBPK models. Improved models could
      be used to further investigate the existence of a methylation threshold for
      arsenic and its relevance to arsenic carcinogenicity in humans. The significance
      of alterations in relative tissue concentrations of SAM and SAH deserves further
      attention, particularly with respect to their role in modulating
      methyltransferases involved in arsenic metabolism and DNA methylation. The
      importance of genetic polymorphisms and nutrition in influencing
      methyltransferase activities must not be overlooked. In vivo models are necessary
      to evaluate these factors; transgenic or knockout models would be particularly
      useful in the investigation of methylation polymorphisms. Further evaluation of
      methylation polymorphisms in human populations is also warranted. Other in vivo
      models incorporating dietary manipulation could provide valuable insight into the
      role of nutrition in the carcinogenicity of arsenic. With more complete knowledge
      of the pharmacokinetics of arsenic metabolism and the mechanisms associated with
      its carcinogenic effects, development of more reliable risk assessment strategies
      are possible. Integration of data, both pharmacokinetic and mechanistic in
      nature, will lead to more accurate descriptions of the interactions that occur
      between the active chemical species and cellular constituents which lead to the
      development of cancer. This knowledge, in turn, will facilitate the development
      of more accurate and reliable risk assessment strategies for arsenic.

PMID- 11330078
TI  - Evidence: its meanings in health care and in law. (Summary of the 10 April 2000
      IOM and AHRQ Workshop, "Evidence": its meanings and uses in law, medicine, and
      health care).

PMID- 11330079
TI  - An epistemologist in the bramble-bush: at the Supreme Court with Mr. Joiner.

PMID- 11330080
TI  - Proof and policy from medical research evidence.
AB  - When judging the benefits and harms of health care and predicting patient
      prognosis, clinicians, researchers, and others must consider many types of
      evidence. Medical research evidence is part of the required knowledge base, and
      practitioners of evidence-based medicine must attempt to integrate the best
      available clinical evidence from systematic research with health professionals'
      expertise and patients' rights to be informed about diagnostic and therapeutic
      options available to them. Judging what constitutes sound evidence can be
      difficult because of, among other things, the sheer quantity, diversity, and
      complexity of medical evidence available today; the various scientific methods
      that have been advanced for assembling, evaluating, and interpreting such
      information; and the guides for applying medical research evidence to individual
      patients' situations. Recommendations based on sound research can then be brought
      forward as either guidelines or standards, and criteria exist by which valid
      guidelines and standards can be developed and promulgated. Nonetheless, gaps and
      deficiencies exist in current guidelines and in the methods for finding and
      synthesizing evidence. Interpreting and judging medical research involves
      subjective, not solely explicit, processes. Thus, developments in evidence-based
      medicine are an aid, but not a panacea, for definitively establishing benefits
      and harms of medical care, and the contributions that medical research evidence
      can make in any clinical or legal situation must be understood in a context in
      which judgment and values, understanding of probability, and tolerance for
      uncertainty all play a role.

PMID- 11330081
TI  - Expertise in law, medicine, and health care.
AB  - As the practice of science-based medical evidence has challenged the medical
      profession to consider the scientific bases for its methods and procedures, on a
      seemingly parallel path, the United States Supreme Court's 1993 decision in
      Daubert v. Merrell Dow Pharmaceuticals has challenged the legal system to
      consider the science underlying claims of medical expertise. This article
      examines how the legal system has responded to that challenge and why the
      response has been more limited than many had expected; the implications of the
      legal system's approach to scrutiny of claims of medical expertise for the
      practice of science-based medical evidence; and, the central elements of any
      meaningful change in legal assessments of expertise in medicine and health care.

PMID- 11330082
TI  - Cost-effectiveness analysis in the courts: recent trends and future prospects.
AB  - This article provides an initial look at how managed care organizations (MCOs)
      might incorporate cost-effectiveness analysis (CEA) into their decision-making
      process and how the courts might respond. Because so few medical liability cases
      directly involve CEA, we must look at other areas of the law to assess potential
      MCO liability for applying CEA. In general negligence cases, courts rely on a
      risk-benefit test to determine customary practice. Likewise, in product liability
      cases, courts use a risk-utility calculus to determine liability for product
      design defects. And in challenges to government regulation, courts examine how
      agencies use CEA to set regulatory policy. The results have been mixed. In
      product liability cases, CEA has led to some punitive damage awards against
      automobile manufacturers. But courts have integrated it in negligence cases
      without generating juror antipathy, and generally defer to agency expertise in
      how to incorporate CEA. The article discusses the implications of these cases for
      MCO use of CEA and outlines various options for setting the standard of care in
      the managed care era.

PMID- 11330083
TI  - Evidence-based medicine and the law: the courts confront clinical practice
      guidelines.
AB  - This article examines how courts are likely to apply evidence-based medicine, and
      particularly clinical practice guidelines (CPGs), in healthcare litigation
      involving quality-of-care and entitlement-to-benefits (coverage) claims.
      Exploring the "politics" of the current situation, it observes that, just as
      clinicians have been reluctant to use CPGs in practice, courts have been, and
      likely will continue to be, slow to apply them in deciding cases., The article
      analyzes extant and proposed statutory approaches to legitimizing and promoting
      courts' use of CPGs. It concludes by renewing the author's earlier and
      controversial proposal to establish a voluntary federal program for certifying
      guidelines and directing courts to give certified CPGs greater weight in
      healthcare litigation.

PMID- 11330084
TI  - What does evidence mean? Can the law and medicine be reconciled?

PMID- 11330085
TI  - Cost-effectiveness analyses: making a pseudoscience legitimate.

PMID- 11330086
TI  - The use of evidence and cost effectiveness by the courts: how can it help improve
      health care?

PMID- 11330087
TI  - From the clinics to the courts: the role evidence should play in litigating
      medical care.

PMID- 11330088
TI  - Demystifying the law/science disconnect.

PMID- 11330089
TI  - The politics of evidence-based medicine.

PMID- 11330090
TI  - Genetic testing is different. Essay review.

PMID- 11330091
TI  - An out-of-focus shot. Budget blueprints present a differing picture for hospitals
      and providers.

PMID- 11330092
TI  - A baby step on joint ventures. IRS gives not-for-profits hope for using tax
      exemption in deals with for-profits.

PMID- 11330093
TI  - More docs disciplined. State medical boards report uptick in actions; consumers'
      group unmoved.

PMID- 11330094
TI  - A local hospital once more. Struggling Pa. facility completes departure from
      UPMC.

PMID- 11330095
TI  - Chipping away at SCHIP. With costs mounting, Idaho cuts outreach for children's
      health program.

PMID- 11330096
TI  - A new twist. Hospitals revamp recruiting efforts to lure prospects with better
      incentives, benefits.

PMID- 11330098
TI  - Down in the ratings. Higher labor costs, stock market woes spur downgrades at
      healthcare firms.

PMID- 11330099
TI  - Bond sales surge still in forecast.

PMID- 11330100
TI  - Privacy surprise. Bush backs tough medical-data standards.

PMID- 11330101
TI  - Holding an empty bag. AHA's e-commerce effort hit by bankruptcy of business
      partner.

PMID- 11330102
TI  - Leaders who inspire.

PMID- 11330104
TI  - CEOs as citizens.

PMID- 11330103
TI  - The inner game. A conversation with Tim Gallwey. Interview by Joe Flower and
      Patrice Guillaume.

PMID- 11330105
TI  - Why strategies fail.

PMID- 11330106
TI  - Organizational learning in health care.

PMID- 11330107
TI  - Six modest proposals.

PMID- 11330108
TI  - A model of cooperation.

PMID- 11330109
TI  - Best practices. Improving health care by sharing data.

PMID- 11330110
TI  - C.A.M. Bridging the gap.

PMID- 11330111
TI  - The five pillars of leadership.

PMID- 11330112
TI  - Honing your values--and your legacy.

PMID- 11330113
TI  - Personality. Good leaders make sure that their organizations, not themselves, are
      the source of inspiration.

PMID- 11330114
TI  - Dialogue. Rethinking physician relations.

PMID- 11330115
TI  - Defining premature ejaculation for experimental and clinical investigations.
AB  - Researchers investigating premature ejaculation (PE) have employed widely diverse
      definitions of it, thereby limiting progress in the field. This study summarizes
      available research on PE, notes patterns that emerge from these studies, compares
      patterns across several types of studies, and suggests a common model for
      defining PE groups to guide future research. We surveyed two bibliographic
      databases, identifying 45 studies employing a definition or description of a PE
      group. From these, we extracted a range of information, including descriptions of
      the participants, recruitment procedures, if PE subtypes were identified,
      operational criteria for PE classification, relationship and partner information,
      and additional inclusion/exclusion criteria. Over 50% of studies reported no
      criteria, or relied on simple self-identification by participants to establish
      the PE group. Quantifiable behavioral criteria were used in 49% of the studies,
      with ejaculatory latency reported most frequently. This measure was also used as
      a criterion more frequently in studies focusing on assessment of sexual response,
      whereas the number of penile thrusts was used more frequently in studies prior to
      1989. Partner information was often included but seldom used as part of the
      assessment procedure. Progress on research and treatment of PE will continue to
      be limited by the absence of commonly accepted criteria for PE group membership
      and by a lack of identification of relevant PE subtypes and etiologies. This
      paper suggests a flowchart, based on data and a rational analysis of 40 years of
      research, for characterizing PE in ways that could assist the development of the
      field.

PMID- 11330116
TI  - Measures of transgender behavior.
AB  - Using factor analysis, we sought to identify the components of transgenderism.
      Subjects were 455 transvestites and 61 male-to-female transsexuals, all
      biological males. A 70-item questionnaire was used, along with other structured
      questions concerning preferred and usual sex partners. Five factors were
      identified and interpreted: Transgender Identity, Role, Sexual Arousal,
      Androallure, and Pleasure. These factors represent the most salient dimensions of
      transgenderism. All five-factor Means for transvestites and transsexuals differ.
      An examination of overlap of group distributions for each factor showed such
      overlap to range from only 6% for Identity to 46% for both Androallure and
      Pleasure. Factor intercorrelations for the obliquely rotated factors ranged from 
      .37 to .27. While transvestites and transsexuals have different lifestyles, their
      transgender cognition and behavior seem constructed upon different combinations
      of the same variables. A second-order analysis of these five factors yielded two
      factors: Sexual Arousal loaded highest on the first factor (.91), and for the
      second the highest loading variable was Androallure (.57). Each of these
      highlights the primary importance of sexual arousal in transgender cognition and
      behavior. Studying possible age effects, we found that the younger versus older
      transvestite groups had significantly different scale Means for Androallure and
      Pleasure; there were no age differences between older and younger transsexuals on
      any of the five scales. Six percent of transvestites reported a male as their
      usual sex partner; 25% of the transsexuals reported a female as their usual sex
      partner. For each group, one-third indicated their usual sex practice was without
      any partner, while only 5% said they preferred this practice. We propose that the
      five variables identified offer a comprehensive approach to the description of
      individual differences in transgender experience and expression.

PMID- 11330117
TI  - Men sex workers and other men who have sex with men: how do their HIV risks
      compare in New Zealand?
AB  - Sex workers have their perspective on HIV transmission, claiming that in general
      they are more similar than different from other people in HIV status and the
      practice of safe sex. Such an assertion of similarity goes against public and
      professional opinion that prostitution is a major vector in the spread of AIDS.
      Taking the sex workers' similarity claim seriously, this paper considers the
      conditions under which it would be valid. We focus on those factors that make a
      population more or less vulnerable to HIV and how they affect its spread into the
      sex work population. Data from New Zealand comparing men sex workers and other
      men who have sex with men is used to evaluate these ideas. Data partially support
      the hypothesis in that these two groups of men are similar with regard to their
      HIV status. We do find the sex workers to be different, however, in their being
      less likely to engage in safe sex practices. We provide an explanation for why
      this has not lead to their having a higher rate of seropositivity.

PMID- 11330118
TI  - Negotiating risks in context: a perspective on unprotected anal intercourse and
      barebacking among men who have sex with men--where do we go from here?
AB  - Recently, an alarming trend toward unprotected anal intercourse has emerged in
      men who have sex with men. A highly dangerous form of unprotected anal
      intercourse, barebacking--the deliberate and conscious choice to engage in anal
      sex without condoms knowing that there are risks involved--has received much
      attention in the gay press. This trend poses new challenges for HIV prevention.
      As the target population changes, prevention interventions must also evolve to
      remain effective. A review of the scientific literature on risk behaviors and the
      popular literature and websites devoted to barebacking suggests that many
      contextual factors influence the decision to engage in unprotected anal
      intercourse. This review examines the most salient contextual factors affecting
      risk behavior in gay/bisexual men. It also identifies four main cohorts and
      predominant contextual factors that appear to motivate unprotected anal
      intercourse in each. In answering the question "where do we go from here," we
      conclude that contextual issues must be addressed in hybrid prevention
      interventions that include harm reduction, motivational interviewing, and
      traditional approaches.

PMID- 11330119
TI  - Depersonalization, self-esteem and body image in male-to-female transsexuals
      compared to male and female controls.
AB  - Whether postoperative male-to-female transsexuals differ in regard to measures of
      self- and body image from a nontranssexual control group was investigated. A
      group of 30 postoperative male-to-female transsexuals and control groups of 30
      males and 30 females completed self-report measures (depersonalization, self
      esteem, gender identity traits, body image). Results showed that transsexuals and
      males scored higher on self-esteem and dynamic body image than the females did.
      No differences between the groups were found in terms of depersonalization and
      satisfaction. Transsexuals and females described themselves as more feminine than
      males. Regarding sex-role orientation, more androgynous subjects were found among
      transsexuals than in the control groups. General satisfaction is associated with
      feminine and masculine traits in transsexuals. Results are discussed in context
      of the function of these personality features for the identity development of
      male-to-female transsexuals.

PMID- 11330120
TI  - Prevalence and patterns of child sexual abuse and victim-perpetrator relationship
      among secondary school students in the northern province (South Africa).
AB  - An investigation into the prevalence and characteristics of child sexual abuse in
      the Northern Province (South Africa) was conducted. A total of 414 secondary
      school students in standard 9 and 10 in three representative secondary schools
      completed a retrospective self-rating questionnaire in a classroom setting. The
      questionnaire asked about childhood sexual abuse and the victim-perpetrator
      relationship. Results shows an overall (N = 414) child sexual abuse prevalence
      rate of 54.2%, 60% for males (N = 193), 53.2% for females (N = 216). Among them,
      86.7% were kissed sexually, 60.9% were touched sexually, 28.9% were victims of
      oral/anal/vaginal intercourse. "Friend" was the highest indicated perpetrator in
      all patterns of sexual abuse. Many victims (86.7%) perceived themselves as not
      sexually abused as a child, and many (50.2%) rated their childhood as "very
      happy." A call is made for more research, publicity, and campaigns in the area of
      child sexual abuse in the Province.

PMID- 11330121
TI  - Challenging medical-legal norms. The role of autonomy, confidentiality, and
      privacy in protecting individual and familial group rights in genetic
      information.

PMID- 11330122
TI  - To tell or not to tell. Legislative imposition of partner notification duties for
      HIV patients.

PMID- 11330123
TI  - Medical malpractice debt in bankruptcy. Is it dischargeable?

PMID- 11330124
TI  - Breach of fiduciary duty lawsuits against MCOs. What's left after Pegram v.
      Herdrich?

PMID- 11330125
TI  - The changing world of HMO liability under ERISA.

PMID- 11330127
TI  - Finance. Liability costs rise.

PMID- 11330128
TI  - Medical/surgical equipments. All eyes on safety.

PMID- 11330129
TI  - Elder care. Robust rebound.

PMID- 11330130
TI  - Who regulates your hospital?

PMID- 11330131
TI  - Emergency services. Rural distress.

PMID- 11330133
TI  - Health Forum Summit. The Leader's Edge.

PMID- 11330132
TI  - Urban health care. A living lab.

PMID- 11330134
TI  - Customer service. Click-on baby pix.

PMID- 11330135
TI  - Pharmaceuticals. Reimports revived?

PMID- 11330136
TI  - The edge of the chasm.

PMID- 11330137
TI  - Keeping patients safe.
AB  - Hospitals are redoubling efforts to prevent medical errors following two
      Institute of Medicine reports and demands by the Leapfrog Group, a consortium of
      major employers. Four providers have highly developed safety strategies and offer
      lessons and examples to hospitals looking for new ways to confront the issue.

PMID- 11330138
TI  - A rural system reinvents its board structure. A new governance framework.

PMID- 11330139
TI  - Revenge of the GPOs.

PMID- 11330140
TI  - Breathing life into a troubled valley.

PMID- 11330141
TI  - The changing face of private retirement plans.
AB  - A rapidly growing public policy concern facing the United States is whether
      future generations of retired Americans, particularly those in the "baby boom"
      generation, will have adequate retirement incomes. One reason is that Social
      Security's projected long-term financial shortfall could result in a reduction in
      the current-law benefit promises made to future generations of retirees. Another
      reason is that many baby boomers will be retiring with employment-based defined
      contribution (DC) plans, as opposed to the "traditional" defined benefit (DB)
      plans that historically have been the predominant source of employer-provided
      retirement income. These factors are likely to reduce the amount of life annuity
      benefits that future retirees will receive relative to current retirees, raising
      questions as to whether other sources of retirement income--such as individual
      account plans (DC plans and individual retirement accounts, or IRAs)--will make
      up the difference. This Issue Brief highlights the changes in private pension
      plan participation for DB and DC plans and provides some possible explanations
      for these changes. Results are presented from the Employee Benefit Research
      Institute's (EBRI) Retirement Income Projection Model that quantify how much the
      importance of individual account plans is expected to increase because of these
      changes. This Issue Brief also discusses the risk of outliving one's assets,
      since a greater fraction of pension wealth is projected to come from
      "nonguaranteed" sources. Results of the model are compared by gender for cohorts
      born between 1936 and 1964 in order to estimate the percentage of retirees'
      retirement wealth that will be derived from DB plans versus DC plans and IRAs
      over the next three decades. Under the model's baseline assumptions, both males
      and females are found to have an appreciable drop in the percentage of private
      retirement income that is attributable to defined benefit plans (other than cash
      balance plans). In addition, results show a clear increase in the income retirees
      will receive that will have to be managed by the retiree. This makes the risk of
      longevity more central to retirees' expenditure decisions. The implications of
      these model results for retirees are significant. First, individuals--rather than
      the pension plan sponsor--increasingly will have to manage their retirement
      assets and bear the risk of investment losses. Second, since most retirees' non
      Social Security retirement income will be distributed as a lump sum or in
      periodic payements (from a defined contribution plan or IRA) rather than as a
      regular paycheck for life (from a defined benefit plan), retirees will need
      either to purchase an annuity from an insurance company or carefully manage their
      individual rate of spending in order to avoid outliving their assets.

PMID- 11330142
TI  - [Miniseries on hypothermia. Newly awaken interest for cold as a therapeutic
      tool].

PMID- 11330143
TI  - [Parkinson disease hits both old and young persons. Cell transplantation to the
      brain is the hope of cure].

PMID- 11330144
TI  - [Hibernation--nature's model of resistance to ventricular fibrillation].
AB  - During hibernation, animals lower their body temperature to a few degrees above 0
      degree C. This means that when entering and emerging from hibernation their body
      temperature passes through the critical level of +20 degrees C, a temperature
      region at which non-hibernating mammals develop circulatory arrest, usually due
      to ventricular fibrillation (VF). The hibernator heart is resistant to VF, not
      only that caused by hypothermia, but also VF as induced by local application of
      aconitine on the epicardium, and also by other factors which ordinarily cause VF
      in non-hibernators. Several mechanisms may explain the resistance to VF observed
      in the hibernator heart. The factors of greatest importance seem to be
      contrasting patterns of adrenergic innervation, divergent physico-chemical
      properties with a lower solidification point of lipids in the hibernator,
      distinct enzyme temperature activity curves seen in the hibernator, and
      differences in the handling of intracellular calcium, resulting in protection
      against calcium overload in the hibernator heart as compared with the non
      hibernator heart.

PMID- 11330145
TI  - [Functionality of inhalation aerosols is inadequate or lost at low temperature].
AB  - Correct and safe performance of metered-dose inhalers are necessary for efficient
      treatment of asthma under all climatic conditions. The spray mechanism
      malfunctioned when canister temperature was below -15 degrees C. The range and
      propagation of the spray plume at canister temperatures below 10 degrees C
      deviated clearly from those at 20 degrees C. Also the composition and particle
      concentration of the spray plume at low temperatures differed from those at more
      normal temperatures. Information must be provided to the effect that a canister
      must not be cold when used.

PMID- 11330146
TI  - [Cold therapy of athletic injuries. Current literature review].
AB  - Cryotherapy is often used in soft tissue sports injuries. The application of a
      cold pack reduces local muscular blood-flow by approximately 50% after 10
      minutes. The duration of bleeding in a muscular injury is not known, but
      immediate application of external pressure is probably far superior in emergency
      treatment of an injury. Some studies have shown significant effect of cryotherapy
      in emergency treatment of ankle sprains, but external pressure is often applied
      simultaneously and the additive effect of cryotherapy is therefore uncertain.
      Cryotherapy reduces the metabolic rate in injured muscle and is often used
      several days after a soft tissue injury to reduce secondary hypoxic injury.
      Experimental studies, however, show no effect of cryotherapy on muscle
      regeneration, and no controlled clinical study has shown a significant effect in
      emergency treatment of soft tissue sports injuries.

PMID- 11330147
TI  - [Drug treatment is beneficial also for elderly patients with Parkinson disease.
      Important to consider also other co-existing diseases].
AB  - Parkinson's disease is a relatively common disorder in elderly patients. With
      carefully performed treatment a considerable improvement can be seen also in
      patients of high age. L-dopa as well as other antiparkinsonian drugs should be
      used in lower doses than those subscribed for younger patients. Cognitive decline
      implies a certain risk for mental confusion, in which case the dose of the
      causing agent has to be lowered or the treatment interrupted.

PMID- 11330148
TI  - [Why researchers excluded women from their trial populations].
AB  - Women are still, but to a lesser extent than twenty years ago, excluded as
      subjects of medical research on diseases that are prevalent among both men and
      women. To discover the basis on which women were excluded, the research ethics
      committee requested a written explanation. In all, 26 such project applications
      were identified during 1997-1999 (2% of the total number of applications during
      the period). Most researchers had more than one reason for exclusion. Qualitative
      analysis revealed that these explanations could be grouped into three categories,
      depending on whether women were excluded for scientific, historical or economic
      reasons. The scientific reasons correspond mainly to a lack of pertinent
      knowledge of the physiology and metabolism of women of childbearing age.
      Consequently, results lacked external validity. Perhaps the lack of knowledge of
      women's physiology and metabolism could be explained by a lack of female
      experimental animals in pre-clinical studies. One notes however a general concern
      not to harm women of childbearing age. The historical reasons underlie the
      tendency to repeat studies on former study populations that happened to be
      composed of men. Finally, tight research budgets restricted the participation of
      women but not of men. The Swedish Medical Research Council issued a policy
      document in 1998 to the effect that research ethics committees could require
      additional information concerning choice of study population. This study
      demonstrates an avoidable occurrence of gender bias in medical research.

PMID- 11330149
TI  - [Labor induction--new solutions of an old problem].

PMID- 11330150
TI  - [Do not minimize signs of postpartum depression! Early intervention essential to
      prevent negative consequences for the child].
AB  - Recent clinical research reveals that postnatal depression is associated with
      disturbances in the mother-infant relationship. These disturbances have in turn
      an adverse impact on the child's cognitive and emotional development. Postnatal
      depression affects 8-15 percent of women in the first months after delivery. The
      use of the Edinburgh Postnatal Depression Scale (EPDS) has proven useful in
      Swedish child health care to help nurses identify mothers with symptoms of
      depression. Weekly counselling visits by trained nurses are effective as the
      first treatment of choice for most women with postnatal depression.

PMID- 11330151
TI  - [Successful gene therapy of experimental type 1 diabetes].

PMID- 11330152
TI  - [Increased social support without any positive effect to new mothers after
      delivery].

PMID- 11330153
TI  - [Ethical problems in connection with organ donation].

PMID- 11330154
TI  - [Do we really want a general one-embryo transfer in IVF?].

PMID- 11330156
TI  - [Beryllium in pulmonary diagnostics].

PMID- 11330155
TI  - [Primary health care in Gothenburg: all can be on the list].

PMID- 11330157
TI  - [Possible exposure to Be should awake the interest].

PMID- 11330158
TI  - [Living will--a death trap?].

PMID- 11330159
TI  - [Reply: Let everybody be happy by his own way].

PMID- 11330160
TI  - [I'm circumcised, but not sexually mutilated!].

PMID- 11330161
TI  - [Circumcision and the standard of the debate].

PMID- 11330162
TI  - [Children's rights and medical ethics].

PMID- 11330163
TI  - [The horse as a consul. Child psychiatry].

PMID- 11330164
TI  - Not good enough, even for orphanages.

PMID- 11330165
TI  - Bytes and bits meet biotech.

PMID- 11330166
TI  - New reading programs spell help for frustrated kids.

PMID- 11330167
TI  - They've got rhythm. Clapping away attention deficits?

PMID- 11330168
TI  - A new niacin. Vitamin with an HDL kick.

PMID- 11330169
TI  - Statins are magic when you gotta have heart.

PMID- 11330171
TI  - A sadly mounting ritual.

PMID- 11330170
TI  - Why there's really no place like home..

PMID- 11330172
TI  - Drama on the polar ice. A risky rescue mission.

PMID- 11330173
TI  - The age of robots.

PMID- 11330174
TI  - A tonic for dementia? Genes for Alzheimer's.

PMID- 11330175
TI  - Therapy by the pound. Human fat is a source of coveted stem cells.

PMID- 11330176
TI  - [Cloning and characterization of CMO gene from Atriplex hortensis].
AB  - Glycine betaine is a widespread osmopretectant existed in many organisms. In
      higher plant, glycine betaine is synthesized via a two-sep oxidation reaction:
      choline-->betaine aldehyde-->glycine betaine. The first step, also the speed
      limiting step, is catalyzed by choline monooxygenase(CMO). Choosing halophyte
      Atriplex hortensis as material, we constructed a salt stress-induced cDNA
      library, and isolated a 1.77 kb length cDNA clone with spinach CMO cDNA as probe.
      The sequencing result showed a complete Open Reading Frame encoding a 438-amino
      acid polypeptide which was 81% and 72% identified to CMO sequences of spinach and
      sugar beet in amino acid homology respectively. Compared with the CMO from
      spinach and sugar beet, the AhCMO had one conserved Rieske-Type [2Fe-2S] cluster
      binding region and one conserved mononuclear Fe-binding motif. The expression
      pattern of AhCMO under salt stress was also stuied, the transcriptional level of
      AhCMO raised about three folds after the plant was treated with brine for 4 days.
      The AhCMO was then transfered into tobacco(Nictiana tabacum var. Xanthi) with 35S
      promotor and seven transgenic plants were certified by northern blot, these
      plants displayed some salt- and drought-stress tolerance when grew well on MS
      medium contained 1.2% NaCl or 10% PEG while the control was stagnated under the
      same cndition.

PMID- 11330177
TI  - [Studies on lipase production from Candida rugosa].
AB  - We studied some factors affecting the lipase production from candida rugosa, they
      mainly included medium compositions and culture condition. The result showed that
      the optimal medium compositions for lipase production are 0.1% glucose 4.0% olive
      oil (carbon source), 0.3% NH4NO3(nitrogen source), 1.2% K2HPO4 and 0.4%
      MgSO4.7H2O. And the optimal culture condition is initial pH6.5, temperature 30
      degrees C, agitation 180 r/min and time 60 h. As a result, and the lipase
      activity could reach 19.5 u/mL. Meanwhile we found that the surfactant could be
      helpful to the lipase production, and the optimal surfactant concentration was
      0.03% GPE. The lipase activity was improved by more than 170% after we optimized
      the medium compositions and culture condition. While in a 5L fermentator, the
      lipase activity of fermentation broth could reach 33.5 u/mL within 48 hours.

PMID- 11330178
TI  - [The establishment of four cell lines from Colossoma brachypomum and their growth
      characteristics under various temperatures].
AB  - Four cell lines originated from embryo, caudal fin, anal fin and snout of
      Colossoma brachypomum were established, and subcultured for 70, 47, 45 and 40
      passages to the present. The results of the experiment indicated that the four
      cell lines were fibroblast-like diploid cells, and the model number of their
      chromosome is 54. These cell lines could grow under temperature of 20-35 degrees
      C, and its optimum temperature was 27-30 degrees C. The cells grew slowly at 20
      degrees C, stopped growth at 15 degrees C, and died below 10 degrees C. This
      indicated that the growth temperature of the these cell lines was coincident with
      that of fish. In addition, the attachment time, doubling time, mitotic index,
      passage survival rate and cell cycle were determined and compared.

PMID- 11330179
TI  - [Continuously perfused cultivation of genetically-engineered CHO cells producing
      prothrombin in a modified Super-Spinner].
AB  - A Super-Spinner was Modified by mounting a stainless steel filter(pore size 75
      microns) to the impeller shaft to retain cells while fresh nutrient is perfused.
      Using Macroporous microcarrier Cytopore 1, continuously perfused cultivation of a
      recombinant CHO cell line, CHO2DS producing prothrombin was performed with the
      perfusion of a protein-free medium DF6S. The cell retention rate was more than
      90% during the 24 days continuously perfused cultivation. The viable cell density
      of CHO2DS and prothrombin concentration reached 4.62 x 10(6)(cells.m/L) and
      11.3(mg/L) respectively after 9 days culture.

PMID- 11330180
TI  - [Cloning of neutral phytase gene nphy from Bacillus subtilis and its expression
      in Escherichia coli].
AB  - The gene encoding the neutral phytase nphy was cloned from Bacillus subtilis by
      polymerase chain reaction (PCR). Nucleotide sequence analysis of nphy revealed
      the presence of an open reading frame of 1152 bp coding for 383 aa. The start
      codon was followed by a sequence coding for a putative signal peptide of 26 aa in
      length. The nphy without original signal peptide encoding sequence was cloned
      into E. coli expression plasmid pTYB40. The result of SDS-PAGE of the phytase
      expressed in E. coli showed that the nphy had been overexpressed. The expressed
      phytase was over 40% of the total soluble protein of E. coli, and has normal
      bioactivity.

PMID- 11330181
TI  - [Study on the expression of pig zona pellucida-3 beta excluding N-terminus signal
      peptide and C-terminus transmembrance-like domain in Escherichia coli].
AB  - Pig oocytes are surrounded by an acellular translucent envelope-zona
      pellucida(pZP), which is comprised of three biochemically and immunologically
      distinct glycoproteins(pZP1, pZP3 alpha and pZP3 beta). Due to the cross
      reactivity of anti-pZP3 beta antibodies with human ZP in vitro, pZP3 beta has
      been considered as potential one of immunogens for developing human contraceptive
      vaccine. In order to express pZP3 beta directly in E. coli; we amplified the core
      fragment of pZP3 beta cDNA by PCR that was deleted 5'- and 3'-terminal sequences
      of coding for signal peptide and transmembrane-like domain. The DNA sequenced
      EcoRI and SalI restriced core fragment was cloned in a frame downstream of PRPL
      promoter in the pBV221 vector. SDS-PAGE analysis showed that pZP3 beta protein
      was expressed especially in E. coli after thermal induction, which the expression
      band displayed the molecular weight of about 38 kD matching with its deduced
      molecular weight(36.5 kD). In addition, the specially expressed protein band on
      SDS-PAGE gel showed specific immunological reaction with anti-pig ZP IgGs of
      rabbit in Western blot.

PMID- 11330182
TI  - [Fusion expression of a peptide antibiotic-apidaecin gene in Lactococcus lactis].
AB  - The ubiquitin fusion of apidaecin was expressed in Lactococcus lactis, using a
      novel nisin-inducible expression system. After induction, a specific band could
      be detected in the extracts of the host strain by Tricine-SDS-PAGE and Western
      blotting. Production of the fusion was up to 7.2% of the total soluble protein of
      the host strain. While the fusion was cut by ubiquitin specific protease-UBP1,
      the product had distinct antibacterial activity.

PMID- 11330183
TI  - [Immunologic properties of coli surface antigen 6(CS6) of enterotoxigenic
      Escherichia coli and cholera toxin subunit B expressed in Shigella flexneri 2a
      strain T32].
AB  - A host-plasmid balancing system composed with a delta asd mutant (FaD) of an
      avirulent strain (T32) of Shigella flexneri 2a and plasmid harboring asd gene was
      used to express enterotoxigenic E. coli surface antigen 6(CS6) and V. cholerae
      toxin subunit B (CTB). The results of Western blotting and ELISA showed that all
      of recombinant plasmids (pYX201, pYX202 and pYX203) could be maintained stably
      and expressed CS6 and CTB respectively in T32 without any antibiotic selection.
      All the recombinant bacterial strains could elicit the corresponding antibodies
      in rabbits. The antibodies against CTB elicited by both FaD/pYX201 and FaD/pYX203
      showed to be high level, and had long prolongation time, in otherwise, the
      antibodies against CS6 showed to be low level, indicating that higher expression
      level of foreign antigen may be benefit for construction of genetic multivalent
      vaccine.

PMID- 11330184
TI  - [Cloning of AHA gene from Amaranthus hypochondriacus and it's aphid inhibitory
      effect in transgenic tabacco plants].
AB  - Using total DNA isolated from Amaranthus hypochondriacus as template, Amaranthus
      hypochondriacus agglutinin AHA gene was amplified by PCR and cloned. Sequence
      analysis results showed that this gene is consisted of 2453 base pairs including
      one 1538 bp intron and two exons of 212 bp and 703 bp respectively. After inverse
      PCR amplification, coding region of AHA gene was obtained. AHA gene with it's
      intron (AHAg) and withou intron (AHAc) were inserted downstream of 35S promotor
      in the binary vector pBin438 resulting in the construction of two plant
      expression vectors pBAHAg and pBAHAc repectively. Leave explants of Nicotinana
      tabacum var. SR1 were transformed with A. tumefaciens LBA4404 harbouring the
      above expression vectors. Results from PCR and Southern blot analysis showed that
      AHA genes were inserted into the genome of transformed tobacco plants. Immunodot
      blot analysis indicated that AHA was expressed in transgenic plants. The results
      from insect bioassay with peach aphid (Mizus persicae) showed that the transgenic
      plants of pBAHAg and pBAHAc were aphid resistant, evidenced by a 57%-48%
      reduction in insect population density, some plants were more than 85%. The aphid
      resistance of transgenic plants transformed with AHAg gene as judged by aphid
      inhibition rate was higher than that of plants transormed with AHAc gene
      indicating that the intron in AHAg may be favorable for expression of AHA in
      transgenic plants.

PMID- 11330185
TI  - [Cucumber mosaic virus cDNA vector expressed foreign genes in tobacco cells].
AB  - Full-length cDNA of SD strain CMV (SD-CMV) RNA 3 was cloned and sequenced. An Nsi
      I site was created at the sequence around the start codon of coat protein (CP)
      gene and a replacement cassette was constructed. The CP gene was replaced by
      green fluorescent protein (GFP) gene, beta-glucuronidase (GUS) gene or mouse
      dihydrofolate reductase (DHFR) gene, respectively. The cDNAs of Fny-CMV RNAs 1
      and 2 and the chimeric SD-CMV RNA 3 were cloned between the 35S promoter and
      terminator separately. Tobacco protoplasts transfected with the CMV cDNA vectors
      expressed the three reporters, implying that CMV could be used as an expression
      vector.

PMID- 11330186
TI  - [Gene chimeric fusion and expression of nucleocapsid NS3 regions and NS4 regions
      of hepatitis C virus genome].
AB  - Genes encoding HCV core and NS4 antigen epitopes and C33c antigen were cloned
      from HCV genome by PCR, respectively. Two fused genes were constructed. One
      contained these three genes, another contained genes encoding C33c antigen and
      NS4 antigen epitopes. These fused genes were cloned into expression plasmid pET
      24(a)+ and pET-22(b)+ under T7 promoter and transformed into E. coli BL21 (DE3)
      respectively. SDS-PAGE analysis revealed that these fused antigens CCN, CN were
      highly expressed after the induction by 1 mmol/L IPTG. These Expression products
      were detected by western blotting with anti-HCV serum.

PMID- 11330187
TI  - [A three-domain antibody fragment VH/L specific to tumor blood vessels].
AB  - AA98 is a specificaally anti-angiogenic antibody generated in our lab. The heavy
      chain variable region (VH) attached with mutagenized 36 nucleotides sequence
      derived from the heavy chain constant region1 (CH1) was amplified VH and light
      chain (L) were inserted into high-level expression vector pET21a successively,
      thus pET21a-VH/L was constructed. VH/L was expressed in E. coli BL21 (DE3) after
      induction with IPTG. The expression of VH/L was 20% of the total bacterial
      proteins. The refolding of VH/L was conducted by dilution and gel filtration
      chromatography. The refolded VH/L could bind to HUVEC specifically. Its affinity
      to the antigen is similar to that of recombinant AA98Fab, but lower than that of
      the parent antibody AA98.

PMID- 11330188
TI  - [Human angiogenin: expression, purification, biological assay].
AB  - Angiogenin cDNA was obtained by RT-PCR, and cloned into the fusion expression
      vector pRSETB. The recombinant Angiogenin protein was fused with His6 at its N
      terminal and expressed as inclusion body. The expression level was about 10% of
      the total bacteria protein. After dissolved in 8 mol/L urea, the recombinant
      protein was purified by Ni2(+)-NTA chelating resin, according to the high
      affinity of His6 with Ni2+. The biological assay indicated that purified rhANG
      could induced the new blood vessel formation of CAM and degraded tRNA in vitro.

PMID- 11330189
TI  - [High cell density culture of phosphotransacetylase mutants of Escherichia coli
      BL21(DE3)].
AB  - Cell culture, organic acid production and foreign protein (TNF) expression of E.
      coli BL21(DE3) and its pta mutant were investigated. Under shaking conditions,
      TNF expression in pta mutant increased by 23%. During the fed-batch culture
      without limitation of specific growth rates, the mutant reached a cell density as
      high as 32.5 g(DCW)/L and total TNF expression at 2.8 g/L, while the parental
      strain only obtained 19.5 g(DCW)/L and 0.84 g/L. The results indicate that
      utility of pta mutant as a host is advantageous in foreign protein expression and
      high cell density culture. Meanwhile, the analysis data of organic acids
      accumulated during fed-batch culture showed that as the decrease of acetate
      production(42% of the parental strain), the accumulation of other organic
      acids(mainly pyruvate, lactate and succinate) obviously increased. As a result,
      the amount of total organic acids increased by 123% over its parent. The lactate
      production may be the main obstacle in further growth of the cells.

PMID- 11330190
TI  - [Co-integration of BLG-LAtPA and WAP improved the expression of LAtPA in
      transgenic mouse milk].
AB  - In order to improve the expression of longer acting tissue plasminogen activator
      in the mammary epithelium of transgenic mice, the fragment of BLG-LAtPA hydrid
      gene was microinjected into mouse embryos with mice whey acid protein gene. Three
      mouse were tested as being Co-integration of BLG-LAtPA and WAP transgene by PCR
      and Southern blot. Milk obtained from lactating females contains biologically
      active tPA, and the concentration of tPA was calculated to be about 10
      micrograms/mL.

PMID- 11330191
TI  - [Cloning and expression of urate oxidase and its application in serum uric acid
      analysis].
AB  - Anurate oxidase (uricase, EC 1.7.3.3) gene from Candida utilis AS2.117 was cloned
      by PCR amplification with primers derived from conserved regions of published
      uicase DNA sequence. The DNA sequence of cloned uricase gene was determined and a
      high homology compared to the reported gene was found. The cloned gene was
      inserted into Bam H I and Nde I sites of pET21a to create the recombinant plasmid
      pURO. In Escherichia coli BL21(DE3) host, the expression lever of uricase reached
      to about 40% of total soluble proteins of the cell. The western blot analysis
      confirmed the result of expression. Properties of the enzyme protein produced by
      E. coli BL21(DE3)/pURO were determined and similar with those of original protein
      from Candida utilis AS2.117. Furthermore, the thermostability of the expressed
      protein was enhanced. The purified recombinant uricase was used in serum uric
      acid analysis.

PMID- 11330192
TI  - [Site-directed mutagenesis at disulfide bond Cys206-Cys210 of prochymosin
      (chymosin)].
AB  - During the work of site-directed mutagenesis at disulfide bond Cys206-Cys210 of
      prochymosin, it was found that the corresponding template sequence had the
      potential to form a loop-stem structure with free energy of -16.1 kcal/mol, which
      prevent the template from pairing with primer and, in turn, the synthesis of the
      mutated DNA strand. Rapid annealing can overcome this difficulty. Five expression
      plasmids of prochymosin muants with deletion of Cys206-Cys210 (C206A, C210A,
      C206A/C210A, C210S and C206S/C210S) were constructed. Except for C206A they were
      expressed at high level in E. coli amounting to 50% of the total cellular
      proteins. Renaturation of the mutant prochymosin indicated that Cys206-Cys210 is
      dispensable for correct refolding of prochymosin. However, the amino acid
      residues at Cys206 and/or Cys 210 play a critical role in determining the
      renaturation. Among the five mutants the reactivation efficiency of C206A/C210A
      were about 4.5-fold, 20-fold and 30-fold higher than that of C206S/C210S, C210A
      and C210S respectively. C206A can not correctly refold at all. CD spectra in the
      far UV region indicate that C206A/C210A and C206S/C210S chymosin analogs have a
      secondary structure almost identical to that of the wild-type chymosin.
      Fluorescence spectroscopic analysis revealed that mutant chymosins have the same
      emission maximum at 333 nm as the wild-type chymosin but their fluorescence
      intensities at 333 nm are much higher than that of the wild-type chymosin.
      Considering that the mutants and the wild-type chymosin exhibit almost the same
      specific activity, it is reasonable to conclude that the mutant proteins assume a
      native active information with a perturbance around some tryptophan residues.

PMID- 11330193
TI  - [Permeabilization of yeast Trigonopsis variabilis FA10 cells for enhancing
      apparent activity of D-amino acid oxidase].
AB  - D-amino acid oxidase(DAO) is an intracellular enzyme in Trigonopsis variabilis
      FA10. The whole cells of yeast exhibited very low DAO activity. Various treatment
      with physical and chemical agents, such as, freezing and thawing, acetone,
      butanol and cetyltrimethylammoinium bromide altered membrane permeability and
      increased cellular DAO activity. It was demonstrated that the performance of
      acetone was dependent on the concentration of the solvent, the incubation time
      and the temperature. Maximum enzyme activity of the cells was achieved with 30
      35% acetone, between 4 degrees C and 28 degrees C. The process was very quick and
      permeabilization occurred in 5 minutes or less. On the other hand, the
      thermostability of DAO in permeabilized cells was higher than in cell extract. It
      was proved that Cephalosporin C could be effectively converted to glutaryl-7ACA
      by permeabilized Trigonopsis variabilis cells with 83% yield.

PMID- 11330194
TI  - [Cloning, expression and preliminary application of a alpha-hydroxynitrile lyase
      from cassave].
AB  - alpha-Hydroxynitrile lyase (ME-HNLs, E.C. 4.1.2.3.37) from the cyanogenic crop
      cassava(Manihot esculentz, Crantz) catalyze the condensation of hydrocyanic acid
      and aldehydes or ketone into (s)-cyanohydrins, which are valuable starting
      material for various optically active compounds, such as pharmaceuticals and
      agrochemicals. The cDNA of a ME-HNL were obtained by RT-PCR and cloned. The
      sequencing result for the cDNA showed that the sequence encoded for the ME-HNL
      was inconsistent with all those which are published, such as hnl10, hnl24, hnl4.
      The full sequence analysis demonstrated that the cloned cDNA was about 75.2%,
      79.8%, 99.2% homologous to other three reported HNL genes from cassava,
      respectively, among which the last was the same to the cloned gene except the
      five base substitution at the site 142, 337, 476, 634 and 636, respectively. The
      two base substitutions lead to change the amino acid sequence, i.e., Ser113-
      >Gly113, Phe158-->Tyr158. To construct the recombinant plasmid pET30a-hnl, the
      cDNA was inserted into an expression vector pET30a. After transformation of
      pET30a-hnl and induction with IPTG, the ME-HNL was efficiently expressed in E.
      coli. BL21 (DE3) and reached over 2100 units/L of culture with the specific
      activity 8.5 u/mg protein. By one simple treatment, incubating 10 minutes at 70
      degrees C, the recombinant ME-HNL may be used as an catalyst for production of
      (S)-mandelonitrile with enantiomeric excess of 95.2% and 98.2% yield.

PMID- 11330195
TI  - [Study on effect of ABA, PEG4000 and AgNO3 on number of somatic embryos of Larix
      Principis-Rupprechtii by 311-A regression design].
AB  - This paper, the effects of ABA, PEG400 and AgNO3 on the number of somatic embryos
      of Larix Principis-Rupprechtii were carried out by 311-A regression design. The
      regression equation was established which expresses the number of somatic embryos
      of Larix Principis-Rupprechtii as function, and the ABA, PEG400 and AgNO3 on as
      variable respectively. Using the regression equation, the single factor effect
      and mutual effect between the number of somatic embryos of Larix Principis
      Rupprechtii and ABA, PEG400 and AgNO3 was studied; the optimum concentration
      recipes can be obtained by computer processing, that are ABA: 18.9138 mg/L,
      PEG400: 88.8007 g/L and AgNO3: 10.7513 mg/L, the target somatic embryos number is
      107.5278 each gram callus. The results of experiment showed that this method is
      simple, practical and rapid for selecting several hormone category and
      concentration recipes media of conifer somatic embryogenesis.

PMID- 11330196
TI  - [A study on the expression of human leptin in the mammary glands of transgenic
      mice].
AB  - Human leptin expressed by E. coli had been used to treat human obesity in
      American and scientists had achieved good effects, the researchers here wanted to
      know whether human leptin can be expressed in the mammary glands of transgenic
      animas. In this study, human leptin gene about 1.0 kb, the terminator of rabbit
      whey acid protein gene (rWAP) about 0.2 kb and the promoter including the distal
      upstream region and part of the first exon of rWAP gene about 6.3 kb were used to
      construct a expression vector. Before we did the subclonings, the sequences of
      the human leptin gene were sequenced by ABI377 DNA Sequencer, the results showed
      that the fragment of human leptin gene included the last nine base pairs of the
      first exon, the complete sequences of the second exon(172 bp) and parts of the
      third exon(including part of the encoding sequences and part of the 3'
      untranslated region). The final expression vector was digested with NotI and a
      fragment of 7.5 kb was collected and dissolved in TE(10 mmol/L Tris.Cl, pH7.4;
      0.1 mmol/L EDTA) for later microinjection. The concentration of DNA was about 2
      micrograms/mL, the copy number in 1 mL was about 2.4 x 10(11), every 1 to 2 pL of
      the prepared DNA solution was microinjected into the mouse embryos at pronucleus
      stage. After standard microinjection procedures, 48 live mice were obtained. The
      tails of the mice were cut(about 0.1 g) at four weeks of age, genomic DNA was
      extracted and digested completely with EcoRI, two were confirmed to be transgenic
      mice(both were female) by Southern hybridization using DIG labeled human leptin
      gene as probe, transgenic rate among the mice born was about 4% (2/48). The two
      female transgenic mice(2# and C3) were mated with nontransgenic male mice. The
      two founder transgenic mice were segregated with their baby mice for at least
      three hours at the fifth day after parturition and were milked by intraperitoneal
      injection of 0.3 IU of oxytocin and udder massage. SDS-PAGE was used to analyze
      whether there were expression of human leptin in the milk of the two founder
      transgenic mice with the milk of non-transgenic mouse at fifth day after
      parturition as control. SDS-PAGE results showed that compared with the control
      there was a new band in both of the founder transgenic mice milk, and its
      molecular weight was about 16 kD, which was quite similar with that of the human
      leptin. The researchers estimated that the expression level of this protein in
      the milk of the transgenic mice was about 1-2 mg/mL.

PMID- 11330197
TI  - [Research on the selecting suspension cell line of higher productivity of
      flavonol glycoside by hypoxia stress as well as the stability in subcultures].
AB  - Investigate the influence of culture media to growth and flavonol glycoside
      synthesis of calli introduced from seedling of Ginkgo biloba. 6 cell lines were
      selected from calli by hypoxia stress. Among these cell lines the best one TZ-1
      which growth index was 4.12 and the flavonol glycoside content was 1.25% in dried
      cell which was enhanced 257.1% compared with callus. The stability in subcultures
      was investigated: The average content of flavonol glycoside was 1.25% in dried
      cells and the growth index was 3.99 during 6 subcultures. Which variation
      coefficient was separately 0.065 and 0.048. The results show that hypoxia stress
      is a efficient method to select suspension cell line of higher productivity of
      flavonol glycoside.

PMID- 11330198
TI  - [Cloning and expression of the genes of glutathione synthetases].
AB  - The genes(gsh-I,gsh-II) for gamma-glutamyl-cysteine synthetase(GSH-I) and
      glutathione synthetase(GSH-II) from Escherichia coli B were amplified by PCR and
      then subcloned into plasmid pUC19 respectively. The DNA fragments harboring gshII
      and gsh I were inserted into plasmid pTrc99A one by one to get a hybrid plasmid
      pTrc-gsh. E. coli BL21 was transformed by pTrc-gsh for expression of the related
      enzymes. Analysis of SDS-PAGE showed that the expected products were expressed.
      E. coli BL21(pTrc-gsh) were incubated at 37 degrees C and pH 7.2 to OD550 = 0.5.
      The conditions were then switched to 34 degrees C and pH6.7 after the addition of
      0.1 mmol/L IPTG. The expressed products were up to 25% of the total protein of
      the bacteria. Acetone-treated cells of the engineered strain could synthesize GSH
      efficiently.

PMID- 11330199
TI  - Influence of fear conditioning on elicited ponto-geniculo-occipital waves and
      rapid eye movement sleep.
AB  - The amygdala plays a central role in fear conditioning, a model of anticipatory
      anxiety. It has massive projections to brainstem regions involved in rapid eye
      movement sleep (REM) and ponto-geniculo-occipital (PGO) wave generation. PGO
      waves occur spontaneously in REM or in response to stimuli. Electrical
      stimulation of the central nucleus of the amygdala enhances spontaneous PGO wave
      activity during REM and the amplitude of both the acoustic startle response and
      the elicited PGO wave (PGOE), a neural marker of alerting. This study examined
      the effects of fear conditioning on REM and on PGOE. On conditioning days, the
      number of REM episodes, the average REM duration and the REM percentage were
      decreased while REM latency was increased. The presentation of auditory stimuli
      in the presence of a light conditioned stimulus produced PGOE of greater
      amplitudes. The results suggest that fear, most likely involving the amygdala,
      can influence REM and brainstem alerting mechanisms.

PMID- 11330200
TI  - Autonomic control during sleep and risk for sudden death in infancy.
AB  - A variety of clinical pathology and experimental animal evidence suggests that
      cerebellar and vestibular structures mediate marked challenges to blood pressure
      and breathing, and are particularly involved in compensatory somatomotor and
      breathing efforts to overcome substantial losses in blood pressure. At least a
      subset of victims of the Sudden Infant Death Syndrome (SIDS), a sleep-related
      disorder, succumbs to a profound bradycardia and hypotension prior to respiratory
      cessation, suggesting a failure of autonomic control, or incompetent compensation
      of somatomotor and respiratory efforts, to overcome the cardiovascular collapse.
      The clinical and neurotransmitter evidence from SIDS victims implicates afferent
      and efferent components within vestibular/cerebellar blood pressure control
      systems in SIDS victims. Experimental evidence from animals suggests vestibular
      and cerebellar structures exercise critical roles in mediating autonomic
      responses to body position and extreme changes in blood pressure. The position
      dependent risk for SIDS, together with the neuropathological evidence, suggests a
      significant role for vestibular/cerebellar structures in mediating the fatal
      outcome for the syndrome.

PMID- 11330202
TI  - A hundred years of narcolepsy research.

PMID- 11330201
TI  - The hypocretin neuron system: an arousal system in the human brain.
AB  - Hypocretins are recently discovered neuropeptides produced by a small group of
      posterior hypothalamic neurons which project widely over the neuroaxis. In this
      study, we note that hypocretin neuron perikarya in the human brain are localized
      to the perifornical region of the posterior hypothalamus, extending into the
      lateral hypothalamus. These neurons lightly innervate all areas of cerebral
      cortex studied in a variable pattern with denser innervation of association
      cortex than primary motor or sensory cortex. There is a dense innervation of
      hypothalamus, locus coeruleus, raphe nuclei, midline thalamus and nucleus of the
      diagonal band-nucleus basalis complex of the forebrain. This pattern of
      projections from the hypocretin neurons is compatible with an important role in
      arousal and the maintenance of the waking state.

PMID- 11330203
TI  - Some considerations on sleep and neural plasticity.
AB  - A role for sleep in memory processes and neural plasticity has been suggested
      many times and in many different forms. However, we are far from a consensus on
      what this role might be and why it would be fulfilled preferentially by sleep. In
      this review, we distinguish between memory acquisition, consolidation, and
      maintenance, and we consider how sleep may specifically contribute to each of
      these phases. We also distinguish between declarative and nondeclarative memories
      and their relationships to different stages of sleep. Finally, we discuss whether
      different molecular and cellular aspects of neural plasticity may be associated
      preferentially with different behavioral states. A consideration of such
      molecular aspects could lead to more conclusive experiments concerning the
      relationship between sleep and plasticity.

PMID- 11330204
TI  - Sleep-wake variations and drug self-administration.

PMID- 11330205
TI  - Sustained attention performance during sleep deprivation: evidence of state
      instability.
AB  - Nathaniel Kleitman was the first to observe that sleep deprivation in humans did
      not eliminate the ability to perform neurobehavioral functions, but it did make
      it difficult to maintain stable performance for more than a few minutes. To
      investigate variability in performance as a function of sleep deprivation, n = 13
      subjects were tested every 2 hours on a 10-minute, sustained-attention,
      psychomotor vigilance task (PVT) throughout 88 hours of total sleep deprivation
      (TSD condition), and compared to a control group of n = 15 subjects who were
      permitted a 2-hour nap every 12 hours (NAP condition) throughout the 88-hour
      period. PVT reaction time means and standard deviations increased markedly among
      subjects and within each individual subject in the TSD condition relative to the
      NAP condition. TSD subjects also had increasingly greater performance variability
      as a function of time on task after 18 hours of wakefulness. During sleep
      deprivation, variability in PVT performance reflected a combination of normal
      timely responses, errors of omission (i.e., lapses), and errors of commission
      (i.e., responding when no stimulus was present). Errors of omission and errors of
      commission were highly intercorrelated across deprivation in the TSD condition (r
      = 0.85, p = 0.0001), suggesting that performance instability is more likely to
      include compensatory effort than a lack of motivation. The marked increases in
      PVT performance variability as sleep loss continued supports the "state
      instability" hypothesis, which posits that performance during sleep deprivation
      is increasingly variable due to the influence of sleep initiating mechanisms on
      the endogenous capacity to maintain attention and alertness, thereby creating an
      unstable state that fluctuates within seconds and that cannot be characterized as
      either fully awake or asleep.

PMID- 11330206
TI  - Evolving concepts of human state dissociation.
AB  - The concept of state dissociation in humans was made possible only by applying
      information obtained from basic science animal research studies to the human
      condition--without which these often dramatic, and treatable conditions would
      have remained in the mystical, supra-natural, or psychiatric arenas, without
      appropriate or effective treatment options. Sleep or wakefulness occurring
      asynchronously in bits and pieces of the brain is a most useful concept. From our
      standpoint, the basic science work in the function and mechanism of sleep is
      pertinent, not only adding to our knowledge in these important areas for the sake
      of knowledge, but also in providing clinicians with important information that is
      of immense clinical importance. The payoff of such research has been great, and
      demands that it should be ongoing. The field of sleep research and sleep medicine
      is in a unique position to foster close interactions between basic scientists and
      clinicians, the result being basic science answers to clinical questions, and
      unanswered clinical questions guiding the direction of and reinforcing the basic
      science research. The clinical conditions discussed above underscore the value of
      close cooperation among those working at all levels: molecular, cellular, multi
      cellular, and clinical. Continued study of state dissociation by both basic
      scientists and clinicians will undoubtedly identify and explain even more of
      these fascinating conditions, with important therapeutic implications. The
      reciprocal benefits of close collaboration between basic scientists and
      clinicians will continue to be realized.

PMID- 11330207
TI  - Extended nights, sleep loss, and recovery sleep in adolescents.
AB  - In summary, this study of sleep in adolescents on an atypical schedule of 18-hour
      nights showed marked but not unanticipated differences in sleep as function of
      prior sleep deprivation. Unanticipated was the evidence of "recovery" sleep in
      adolescents who not only were not sleep deprived, but who had been on a sleep
      "optimizing" schedule and had been awake for only 10 hours. Extended sleep
      beginning about 4 hours in advance of entrained sleep onset phase was not
      associated with a return of SWS, a finding coinciding with predictions from
      studies in adults. Finally, this study provides an indication that the
      homeostatic sleep/wake process becomes less robust or sleep responsive during
      adolescent development, a phenomenon that may influence the delay of sleep common
      in adolescents.

PMID- 11330208
TI  - Microdialysis perfusion of orexin-A in the basal forebrain increases wakefulness
      in freely behaving rats.
AB  - Recent work indicates that the orexin/hypocretin-containing neurons of the
      lateral hypothalamus are involved in control of REM sleep phenomena, but site
      specific actions in control of wakefulness have been less studied. Orexin
      containing neurons project to both brainstem and forebrain regions that are known
      to regulate sleep and wakefulness, including the field of cholinergic neurons in
      the basal forebrain (BF) that is implicated in regulation of wakefulness, and
      includes, in the rat, the horizontal limb of the diagonal band, the substantia
      innominata, and the magnocellular preoptic region. The present study used
      microdialysis perfusion of orexin-A directly in the cholinergic BF region of rat
      to test the hypothesis that orexin-A enhances W via a local action in the BF. A
      significant dose-dependent increase in W was produced by the perfusion of three
      doses of orexin-A in the BF (0.1, 1.0, and 10.0 microM), with 10.0 microM
      producing more than a 5-fold increase in wakefulness, which occupied 44% of the
      light (inactive) phase recording period. Orexin-A perfusion also produced a
      significant dose-dependent decrease in nonREM sleep, and a trend-level decrease
      in REM sleep. The results clearly demonstrate a potent capacity of orexin-A to
      induce wakefulness via a local action in the BF, and are consistent with previous
      work indicating that the BF cholinergic zone neurons have a critical role in the
      regulation of EEG activation and W. The data suggest further that orexin-A has a
      significant role in the regulation of arousal/wakefulness, in addition to the
      previously described role of orexin in the regulation and expression of REM sleep
      and REM sleep-related phenomena.

PMID- 11330209
TI  - Aging, texture segmentation, and exposure duration: evidence for a deficit is
      preattentive processing.
AB  - Younger and older observers were asked to detect the presence and identify the
      orientation of an orientation-based texture target presented at durations ranging
      from 15 to 75 ms. In Experiment 1a, an age by duration interaction indicated that
      older adults were less able to process the displays at short durations. In
      Experiment 1b, a group of younger adults was given the task under conditions
      designed to simulate age-related changes in retinal illuminance. Their
      performance was independent of luminance, and was still superior to that of older
      adults in Experiment 1a. Several mechanisms are potential contributors to these
      age deficits in lower-level processing that can influence higher-level visual
      perception.

PMID- 11330210
TI  - Language processing, slowing, and speed/accuracy trade-off in the elderly.
AB  - Previous studies have suggested that longer response times in older adults could
      be partly due to increased caution in responding, with a propensity to emphasize
      accuracy to the detriment of speed. A study was carried out in 30 young and 30
      older adults in order to determine whether shifting the response criterion
      relative to the speed/accuracy trade-off towards a more risky strategy would
      significantly reduce age-related differences in response time. The experimental
      procedure involved the detection of incongruous sentences, either with or without
      a mnemonic preload. Instructions emphasized alternatively speed or accuracy.
      Results showed that whatever the instructions, older adults remained consistently
      much slower than young adults, and a little more accurate. When instructed to
      emphasize speed, they never managed to reduce the response time difference
      relative to young adults. It is concluded that the more cautious approach in
      older adults is required to attenuate the adverse effects of a slower processing
      system.

PMID- 11330211
TI  - Age effects on analogy-based memory for text.
AB  - We examined age influences on analogy-based learning, in particular, analogy
      based text memory. Adults (20-72 years) read pairs of passages describing
      analogous topics. We manipulated encoding complexity for the first passage and
      superficial topic similarity between passages, and assessed second-passage
      memory. Across all age groups, memory was better in the superficially similar
      topic condition only when encoding complexity had been simple. More critically,
      performance was better for similar topics only for the youngest adults. Younger
      adults performed worse than older adults in the dissimilar condition. Thus, only
      older adults identified and used the parallels between passages spontaneously.

PMID- 11330212
TI  - Cognitive construct measurement in small samples of younger and older adults: an
      example of verbal working memory.
AB  - An important issue in experimental aging research is the accurate measurement of
      cognitive constructs, particularly in small-sample studies. Latent variable
      modeling approaches to assessing age-based construct similarity are difficult to
      implement in smaller-scale studies, which tend to have small samples and
      measurement of a single construct. We discuss factor score comparison methods for
      assessing age-based construct similarity that may be more appropriate for small
      scale studies. We then examine these methods for a series of single-factor models
      of verbal working memory (VWM) based on data from three separate studies in which
      small samples of younger and older adults' completed VWM-based tasks. Our single
      factor models accounted well for the associations among the sets of VWM tasks.
      This construct was also measured well across age groups and different samples.
      Our analyses suggest that factor score comparison methods may be useful for small
      scale studies that require assessment of age-based measurement similarity in
      cognitive constructs.

PMID- 11330213
TI  - Perceived stress and coping resource availability as predictors of life
      satisfaction in young, middle-aged, and older adults.
AB  - Global satisfaction with life across three age groups (18 to 40 years, 41 to 65
      years, and 66 years and above) was investigated. Multiple regressions were
      computed to examine the separate and joint effects of perceived stress and coping
      resource availability upon life satisfaction across the three age groups (N =
      189). Age differences in perceived stress, coping resource availability, and life
      satisfaction, were also investigated. Results of this cross-sectional
      investigation indicated that self-appraisal measures of perceived stress and
      coping resource effectiveness served as moderate predictors of global life
      satisfaction, and that for the total sample the combined effects of perceived
      stress and coping resource effectiveness were better predictors of life
      satisfaction than either variable considered separately. Perceived stress was
      found to be a better predictor of life satisfaction for younger adults, and
      coping resource effectiveness was a better predictor of satisfaction with life
      for middle-aged and older adults. Significant age differences in life
      satisfaction, perceived stress, and coping resources were also found. The
      assessment of perceived stress and coping has important implications for life
      satisfaction among all age groups, and has particular significance to older
      adults. By identifying age differences in variables associated with satisfaction
      with life, more effective efforts can be made to promote physical and
      psychological well-being in late adulthood.

PMID- 11330214
TI  - Adulthood relocation: implications for personality, future orientation, and
      social partner choices.
AB  - The purpose of this study was to learn the reasons why individuals relocate and
      whether relocaters differ from nonrelocaters on demographic, social, and
      personality factors. One hundred participants from three age groups, 34 to 46
      (young/middle-aged), 54 to 66 (young-old), and 69 to 93 (older) years, were
      designated as relocaters or residents as a function of months of residence.
      Relocaters did not differ from residents in age, income, health, or marital
      status. Reasons provided for relocating revealed the following differences:
      young/middle-aged moved for employment reasons, young-old moved for reasons of
      retirement, and older adults relocated to be closer to family members. No
      differences in network size occurred and older relocaters selected more cards in
      a social partner selection task. Most interesting was the finding that relocaters
      scored higher on Openness to Experience and future orientation. These data
      suggest personality may be an important trait that explains why some individuals
      are more likely to relocate.

PMID- 11330215
TI  - Sevoflurane anesthesia in a myasthenic patient undergoing transsternal
      thymectomy.
AB  - Myasthenia gravis (MG) is an autoimmune disease resulting from the production of
      antibodies against the acetylcholine receptors of the neuromuscular synapse. The
      thymus gland is involved in the autosensitization process, and there is a
      consensus that all adults with generalized MG should have a thymectomy. Removal
      of a much thymic tissue as possible via the transsternal approach in the logic
      goal of thymectomy in the treatment of MG. Because of the unpredictable response
      to succinylcholine and the marked sensitivity to nondepolarizing muscle relaxants
      in the MG patients, some anesthesiologists avoid the use of muscle relaxants in
      the myasthenic patients, and depend on deep inhalation anesthesia, such as
      halothane, isoflurane or sevoflurane. In the present report, we used sevoflurane
      4%, without supplementation by muscle relaxants, for the induction and
      maintenance of anesthesia in a MG patient undergoing transsternal thymectomy. The
      report reviews the anesthetic technique, and describes the electromyographic
      (EMG) changes following sevoflurane.

PMID- 11330216
TI  - Anaesthetic management of emergency caesarean section in a patient with Noonan's
      syndrome--case report and literature review.
AB  - Patients with Noonan's syndrome present a multiplicity of challenges to the
      anaesthetist, particularly with regard to cardiovascular, spinal, and airway
      abnormalities. Anaesthetist may have to deal with an increasing number of these
      patients presenting to anaesthesia departments requesting analgesia and
      anaesthesia for surgery of labour. Early detection and planing between
      obstetricians, midwives and anaesthetists will help successful management of
      these patients. Alternative methods of management should be discussed fully with
      patients. Regional anaesthesia, although may be difficult in these patients, is a
      safe alternative compared to expensive general anaesthesia.

PMID- 11330217
TI  - A new cut-off point of thyromental distance for prediction of difficult airway.
AB  - BACKGROUND: Difficult intubation, often unexpected, remains a primary concern for
      the anesthesiologist. None of the bedside tests have proven to be efficacious and
      highly predictive. The prupose of this study was to correlate the full range of
      thyromental distance with both the Cormack grade and the Mallampati score.
      METHODS: One hundred and sixty patients undergoing general anesthesia were
      included in the study. Patients with abnormal atlanto-occipital extension, small
      chin size and mouth opening were excluded from the study. The thyromental
      distance, the Mallampati score, and the Cormack grade were determined in all
      patients. The correlation between the thyromental distance and each of the
      Cormack grade and the Mallampati score was determined, as well as the correlation
      between the Mallampati score and the Cormack grade. The cut-off value of the
      tyromental distance that discriminated best between patients with easy glottic
      visualization (Cormack grade 1,2) vs. difficult visualization (Cormack grade 3,4)
      was derived. RESULTS: A significant and high correlation was observed between the
      thyromental distance and the Cormack grade (r = -0.72). In contrast, a lower
      correlation was observed between the thyromental distance and the Mallampati
      score (r = -0.41) and the Mallampati score and the Cormack grade (r = 0.47). A
      cut-off value for the TMD of 4 cm was the best in discriminating between patients
      with difficult and easy glottic visualization. The combination of TMD < or = 4 cm
      and Mallampati score of 3,4 predicted the patients with the most difficult
      glottic visualization. CONCLUSION: Patients with a thyromental distance greater
      than 4 cm can be easily intubated. In contrast, when the TMD < or = 4 cm,
      tracheal intubation is difficult in 48% of patients if the Mallampati score is
      1,2 and in 79% if the Mallampati score is 3 or 4.

PMID- 11330218
TI  - Spontaneous chylothorax--case report.
AB  - A-19-year old male patient complained of shortness of breath. Aspiration of the
      pleural fluid revealed chylothorax. Right chest tube was inserted. His ABG showed
      hypoxaemia with relative hypercarbia. He underwent right thoracotomy and thoracic
      duct ligation under general anaesthesia and double lumen endobroncheal
      intubation. During surgery he lost 1.5 L of blood and 4 L chyle. He was
      transferred to the SICU intubated and on mechanical ventilation. On the
      subsequent days chyle leak was reduced to a minimum of 10 ml/hr. On the 9th
      postoperative day the patient was extubated. He was receiving TPN 2600 kcal/day.
      He was transferred to the normal floor on the 15th day. After 7 day he was
      readmitted, his chest showed severe lung fibrosis and consolidation. His ABG
      showed severe hypercarbia (PaCO2 = 126 mmHg). The patient was intubated. His
      condition deteriorated and he was considered for lung transplantation. No donor
      was available. Later he arrested and died. Anaesthesia and surgical management of
      spontaneous chylothorax is challenging. The mortality rate is high.

PMID- 11330219
TI  - A successful management of a case of difficult intubation using Magboul
      laryngoscope.

PMID- 11330220
TI  - Garlic extract (allium sativum) reduces migration of neutrophils through
      endothelial cell monolayers.
AB  - Leukocytes play an important role during inflammation. They migrate from
      intravascular spaces into tissues and attack micro-organisms. In a recent study,
      the inhibitory effects of the non-steroidal anti-inflammatory drug, ibuprofen, on
      leukocyte transmigration were demonstrated using an in vitro assay. Little is
      know about the cellular effects of garlic extracts (allium sativum). The aim of
      the current study was to investigate the influence of garlic extract on leukocyte
      migration through endothelial cell monolayers and thereby evaluate a possible
      role in inflammatory processes. Human umbilical endothelial cells were cultured
      on microporous membranes to make an endothelial cell monolayer (ECM). Freshly
      isolated neutrophils were used in a recently described migration assay. The
      amount of untreated neutrophils migrating through the untreated ECM was used as
      control and set at 100%. Neutrophils and/or ECM were pre-treated with garlic
      extract using moderate, as well as higher and lower concentrations. Moderate
      plasma concentrations garlic extract inhibited neutrophil migration through ECM
      significantly (64 +/- 5.8% SD; P < 0.05), when both cell types were treated, (a
      situation that may have clinical relevance). Treating either neutrophils or ECM
      alone showed significant reductions in migratory rate (neutrophils treated alone:
      81 +/- 7.7% SD, p < 0.05; ECM alone: 70 +/- 6.7%, p < 0.05). Thus, garlic extract
      is identified as a potent inhibitor of leukocyte migration through endothelial
      cell monolayers. Treatment of both cell types has an additive effect. Endothelial
      cells seem to be more affected than neutrophils. Further investigations are
      necessary to understand the potential clinical consequences. During inflammation,
      neutrophils play an important role. They migrate rapidly from the vascular space
      into tissues to destroy invading micro-organisms. During migration through
      endothelial cell monolayers (ECM), neutrophils undergo morphologic changes from
      rounded, relatively smooth cells to elongated, ruffled cells with pseudopodia.
      Recently, the influence of the non-steroidal anti-inflammatory drug, ibuprofen,
      on leukocyte function was investigated using an in vitro double chamber migration
      assay that includes ECM. Garlic extract (allium sativum) is a widely used "over
      the counter" herbal preparation. The effect of garlic on lipid metabolism is well
      documented. Previous studies have examined the influence of the extract on
      leukocyte function, e.g. respiratory burst. The effect of garlic on thrombocyte
      aggregation has also been recently described as has an anti-fungal effect. To our
      knowledge, nothing is known about the effect of garlic leukocyte transmigration.
      Therefore, we aimed to examine the effects of garlic extract on leukocyte
      transmigration through ECM in an in-vitro cell co-culture system.

PMID- 11330221
TI  - The controversy about the routine use of thoracic epidural anaesthesia and
      analgesia in coronary artery bypass graft surgery.

PMID- 11330222
TI  - Foreign body retrieval in children with respiratory symptoms and no history of
      aspiration.
AB  - To asses the role of bronchoscopy and its yield in children with respiratory
      symptoms and no typical history of radiological evidence of foreign body
      aspiration (FBA), we reviewed the records of all patients who underwent
      bronchoscopy at our institution between 1985 and 1995 and had no history of
      choking, witnessed FBA or clear radiological evidence of FBA (N = 54, age range 4
      months to 16 years). These were subdivided into two subgroups, those with
      positive bronchoscopy, and those with negative bronchoscopy. Respiratory symptoms
      and their duration, signs and radiological findings did not differ in both
      subgroups.

PMID- 11330223
TI  - Succinylcholine-induced rhabdomyolysis in a healthy child.
AB  - A case of Rhabdomyolysis occurred in a healthy boy 9 years of age after general
      anaesthesia. Succinylcholine, nitrous oxide and isoflurane were used for
      induction and maintenance of anaesthesia. Patient developed severe muscle pain,
      myoglobinuria, haemoglobinuria. Also creatinine phosphokinase was elevated up to
      10,694 IU/L. Management was prompt and he was discharged home the third day in
      good condition. The injection of succinycholine may have precipitated
      rhabdomyolysis. This is a rare complication of succinylcholine without the
      disastrous outcome of renal failure, hyperkalaemia or cardiac arrest.

PMID- 11330224
TI  - Endotracheal tube introducer: an aid for the difficult airway.

PMID- 11330225
TI  - Health care consumers say they want to know more objective measures about
      quality.
AB  - Contrary to popular belief, average health care consumers are focused on more
      than just service quality and access to care when evaluating health care systems,
      hospitals, and providers. Instead, consumers are more likely to want objective
      measures of evidence-based care and clinical performance to help them better
      evaluate their health care providers, according to a new report, "Consumer Demand
      for Clinical Quality: The Giant Awakens," from VHA, Inc.

PMID- 11330226
TI  - Minnesota payers agree to work on same page with medical protocols.
AB  - In March, five of Minnesota's largest health plans--Blue Cross and Blue Shield of
      Minnesota, Medica, Preferred One, UCare Minnesota, and HealthPartners--agreed to
      work together as sponsors of the Institute for Clinical Systems Improvement to
      use best medical practice protocols developed at the institute.

PMID- 11330227
TI  - Creating a safer workplace to provide quality care.
AB  - In recent years, increasing interest has been placed on how health care workers
      can be trained and equipped to better protect them from possible workplace
      accidents and injuries while improving the care they deliver. Better workplace
      safety also means better customer and employee satisfaction, improved workforce
      retention and recruitment, and cost savings. Workplace safety is constantly
      evolving and addresses a whole host of issues ranging from needles and sharps
      injuries to moving patients to human factor analyses. This issue takes a cross
      sectional look at how hospitals and health systems are addressing problem areas-
      and sharing information and best practices--to strengthen their quality of care
      at the workplace level.

PMID- 11330228
TI  - High-stakes testing in employment, credentialing, and higher education. Prospects
      in a post-affirmative-action world.
AB  - Cognitively loaded tests of knowledge, skill, and ability often contribute to
      decisions regarding education, jobs, licensure, or certification. Users of such
      tests often face difficult choices when trying to optimize both the performance
      and ethnic diversity of chosen individuals. The authors describe the nature of
      this quandary, review research on different strategies to address it, and
      recommend using selection materials that assess the full range of relevant
      attributes using a format that minimizes verbal content as much as is consistent
      with the outcome one is trying to achieve. They also recommend the use of test
      preparation, face-valid assessments, and the consideration of relevant job or
      life experiences. Regardless of the strategy adopted, it is unreasonable to
      expect that one can maximize both the performance and ethnic diversity of
      selected individuals.

PMID- 11330229
TI  - Politicized collective identity. A social psychological analysis.
AB  - This article develops a social psychological model of politicized collective
      identity that revolves around 3 conceptual triads. The 1st triad consists of
      collective identity, the struggle between groups for power, and the wider
      societal context. It is proposed that people evince politicized collective
      identity to the extent that they engage as self-conscious group members in a
      power struggle on behalf of their group knowing that it is the more inclusive
      societal context in which this struggle has to be fought out. Next, 3 antecedent
      stages leading to politicized collective identity are distinguished: awareness of
      shared grievances, adversarial attributions, and involvement of society at large.
      This sequence culminates in the final triad because the intergroup power struggle
      is eventually triangulated by involving society at large or representatives
      thereof. Consequences of politicized collective identity are discussed.

PMID- 11330230
TI  - Creativity for the new millennium.

PMID- 11330231
TI  - Beyond talent. John Irving and the passionate craft of creativity.
AB  - Although laypeople and creativity theorists often make the assumption that
      individual creativity depends primarily on talent, there is considerable evidence
      that hard work and intrinsic motivation--which can be supported or undermined by
      the social environment--also play central roles. In this article, the author uses
      the thoughts and work of the novelist John Irving to illustrate the prominence of
      nontalent components in the componential model of creativity.

PMID- 11330232
TI  - Catalytic creativity. The case of Linus Pauling.
AB  - This article illustrates how creativity is constituted by forces beyond the
      innovating individual, drawing examples from the career of the eminent chemist
      Linus Pauling. From a systems perspective, a scientific theory or other product
      is creative only if the innovation gains the acceptance of a field of experts and
      so transforms the culture. In addition to this crucial selective function vis-a
      vis the completed work, the social field can play a catalytic role, fostering
      productive interactions between person and domain throughout a career. Pauling's
      case yields examples of how variously the social field contributes to creativity,
      shaping the individual's standards of judgment and providing opportunities,
      incentives, and critical evaluation. A formidable set of strengths suited Pauling
      for his scientific achievements, but examination of his career qualifies the
      notion of a lone genius whose brilliance carries the day.

PMID- 11330233
TI  - Oscillations and analogies. Thomas Young, MD, FRS, genius.
AB  - Thomas Young is arguably one of the greatest geniuses who ever lived, but most
      people have never heard of him, though he was renowned in his own era. He did
      important work in a large variety of scientific disciplines, but that was his
      downfall. Given the specialization of the present era, physicists do not
      appreciate how important his work in linguistics was, linguists do not appreciate
      the importance of his work in psychology, and so on. Despite his obscurity today,
      Young nicely exemplifies the traits that one finds in a genius of the first
      order: tendency toward analogical thinking, high intelligence, an amazing
      capacity for hard work, extremely wide interests, distaste for traditional
      dogmas, and very high self-esteem.

PMID- 11330234
TI  - Creative work. The case of Charles Darwin.
AB  - The evolving systems approach (ESA) addresses the need for direct study of the
      creative process in recognized creators at work, in contrast to indirect methods,
      such as those used in psychometric studies. The ESA emerged from H. E. Gruber's
      prolonged study of Charles Darwin's manuscripts, especially the notebooks he kept
      after the Beagle voyage. Gruber's interviews with J. Piaget about the latter's
      creative processes, as well as many doctoral dissertations, also helped shape the
      authors' approach. Using Gruber's (1974/1981) study of Darwin, the authors
      describe some facets of creative work identified in the course of their work.
      Among these are networks of enterprise, ensembles of metaphors, insights, and
      evolving belief systems. Although the ESA emphasizes cognitive processes, social,
      affective, and esthetic aspects of the case are not neglected. Each creative case
      is unique, otherwise the individual would not meet the criterion of originality.
      Uniqueness does not mean isolation; people who differ must and do work together.
      The integration of all these facets into a plausible system for each creator
      remains the authors' central task.

PMID- 11330235
TI  - Creative cognition, conceptual combination, and the creative writing of Stephen
      R. Donaldson.
AB  - This article explores the reported use of conceptual combination in Stephen R.
      Donaldson's development of the idea for his award-winning fantasy series. The
      Chronicles of Thomas Covenant the Unbeliever. Donaldson's (1991) own account is
      used to illustrate the general principles of a creative cognition approach to
      understanding creativity as well as the more specific role of the basic process
      of conceptual combination. The links between Donaldson's and others' anecdotal
      accounts of creativity and laboratory investigations are assessed. The article
      concludes with an argument for a "convergence" approach in which information from
      anecdotal accounts and laboratory studies is combined to provide a more complete
      picture of creative functioning than either approach alone can offer.

PMID- 11330236
TI  - Variability, constraints, and creativity. Shedding light on Claude Monet.
AB  - Recent experimental research suggests 2 things. The first is that along with
      learning how to do something, people also learn how variably or differently to
      continue doing it. The second is that high variability is maintained by
      constraining, precluding a currently successful, often repetitive solution to a
      problem. In this view, Claude Monet's habitually high level of variability in
      painting was acquired during his childhood and early apprenticeship and was
      maintained throughout his adult career by a continuous series of task constraints
      imposed by the artist on his own work. For Monet, variability was rewarded and
      rewarding.

PMID- 11330237
TI  - What is the common thread of creativity? Its dialectical relation to intelligence
      and wisdom.
AB  - Creativity refers to the potential to produce novel ideas that are task
      appropriate and high in quality. Creativity in a societal context is best
      understood in terms of a dialectical relation to intelligence and wisdom. In
      particular, intelligence forms the thesis of such a dialectic. Intelligence
      largely is used to advance existing societal agendas. Creativity forms the
      antithesis of the dialectic, questioning and often opposing societal agendas, as
      well as proposing new ones. Wisdom forms the synthesis of the dialectic,
      balancing the old with the new. Wise people recognize the need to balance
      intelligence with creativity to achieve both stability and change within a
      societal context.

PMID- 11330238
TI  - What about the statins?

PMID- 11330239
TI  - Cost-effectiveness of statin medications.

PMID- 11330240
TI  - Falling off the edge of the modern world?

PMID- 11330241
TI  - The modern, the postmodern, and George Kelly's personal construct psychology.

PMID- 11330242
TI  - Where there is no middle ground.

PMID- 11330243
TI  - Modernity, postmodernity, and psychology.

PMID- 11330245
TI  - [Contribution to the ethical appraisal of xenotransplantation with respect to
      protection of the dignity of the animals].

PMID- 11330244
TI  - TERIMA-2: national extension of thrombolytic treatment with recombinant
      streptokinase in acute myocardial infarct in Cuba.
AB  - AIM: The extension of recombinant streptokinase (rSK) use in Cuba and to evaluate
      its effect on in-hospital mortality of patients with acute myocardial infarct
      (AMI). METHODS: A phase IV clinical study was performed in 52 hospitals from the
      14 Cuban provinces. Patients (any age) with ST segment elevation or bundle branch
      block were included if they came less than 12 h after the onset of AMI symptoms,
      without contraindications for thrombolytic therapy. They received 1.5 x 10(6) IU
      of rSK (Heberkinasa, Heberbiotec, Havana) intravenously, during one hour.
      Endpoints were death due to cardiac (pump failure, wall rupture, arrhythmia) or
      any cause and cardiovascular events at hospital release. RESULTS: The study
      included 2,923 patients, 22-98 years-old, 74.4% men, which represented 37.2% of
      the total AMI patients attended at the participating hospitals from November 1992
      to May 1995. Aspirin was given to 92.5% and betablockers to 65.3%. AMI was
      confirmed in 93.5% of the patients. The mean symptoms--rSK infusion time interval
      was 5.25 h (22.3% of the patients treated within the first 3 h). 302 patients
      died, 80.1% of them due to cardiac causes, 12 attributed to rSK treatment, and 16
      to non-cardiac causes. This 10.4% mortality represents a 4% absolute and a 28.3%
      relative reduction (179 lives saved per year) as compared to a survey made before
      rSK treatment was introduced. In a logistic regression analysis, mortality was
      favored by age, symptoms--infusion time. Killip class, and not having taken
      aspirin or betablockers. Feminine gender was close to the limit of significance.
      The more frequent adverse events were arrhythmias and hypotension during
      infusion. Major bleeding occurred in 27 patients (9 strokes). CONCLUSION: Local
      recombinant-DNA biotechnology can influence on a major health problem with
      favorable cost/ and risk/benefit balances, not possible in a developing country
      with an imported drug. The further extension of this treatment in the country is
      feasible and recommended, monitored through an appropriate pharmacosurveillance
      program.

PMID- 11330246
TI  - Theoretical and practical aspects of animal ethics.

PMID- 11330247
TI  - Bibliography. Current world literature. Epidemiology and health-related services.

PMID- 11330248
TI  - Bibliography. Current world literature. Nonarticular rheumatism, sports-related
      injuries, and related conditions.

PMID- 11330249
TI  - Confirmed group B streptococcus infection: the tip of the iceberg.

PMID- 11330250
TI  - NIR observes infants' brains.

PMID- 11330251
TI  - Finding fossils in the brain.

PMID- 11330252
TI  - Connecting the dots: standards for DNA analysis.

PMID- 11330253
TI  - A comparison of outcomes in osteoarthritis patients undergoing total hip and knee
      replacement surgery.
AB  - OBJECTIVE: The aims of this study were to assess changes in physical function and
      quality of life with the Western Ontario and McMaster Universities Osteoarthritis
      Index (WOMAC) and the instrument of the Medical Outcomes Study SF-36 Health
      Survey (MOS SF-36), respectively, in patients undergoing hip anf knee joint
      replacement surgery and to compare the responsiveness of these two outcome
      measures 1 year after surgery. DESIGN: One hundred and ninety-four patients with
      osteoarthritis (OA knee 108, OA hip 86) admitted to four hospitals in Sydney were
      followed over a period of 1 year at 3 monthly intervals. RESULTS: WOMAC measures
      improved significantly after 1 year for OA hip and OA knee: there was reduction
      in pain of 71% and 53%, reduction of stiffness of 55% and 43% and improvement in
      physical function of 68% and 43%, respectively. MOS SF-36 measures in those
      having hip surgery improved significantly for pain (222%), physical function
      (247%), physical role functioning (402%), general health (110%), vitality (143%0,
      social functioning (169%) and mental health (114%). For those in the knee surgery
      group, significant improvement was seen for pain (175%), physical function
      (197%), physical role functioning (275%), vitality (125%) and social functioning
      (119%). The WOMAC was a more responsive measure than the MOS SF-36. CONCLUSION:
      WOMAC and MOS SF-36 detect significant and clinically meaningful changes in
      outcome after hip and knee replacement. WOMAC requires a smaller sample size and
      is more responsive in the short term. For a follow-up longer than 6 months MOS SF
      36 provides additional information. The improvement in outcomes following hip
      joint surgery were significantly greater than those following knee surgery.

PMID- 11330254
TI  - An audit of the 'two glass' test of urethritis.

PMID- 11330255
TI  - An audit of the 'two glass' test of urethritis.

PMID- 11330256
TI  - Causes and consequences of hypoxia and acidity in tumors--Novartis Foundation
      symposium.

PMID- 11330257
TI  - Disability advocates disappointed by Supreme Court ruling.

PMID- 11330258
TI  - NAMI publishes legal manual on protecting rights of consumers in managed care
      systems. National Alliance for the Mentally Ill.

PMID- 11330259
TI  - The incidence of dieting amongst adolescent girls: a question of interpretation?
AB  - AIM: It is the intention of this study establish the extent of dieting practices
      amongst adolescent girls and identify their perceptions with regard to 'dieting'
      and 'healthy eating'. METHODS: A total of 140 girls, aged 12-13 years, were
      recruited from two schools. A self-reported questionnaire, which determined the
      incidence of dieting and sought to identify the girls' perceptions of 'dieting'
      and 'healthy eating', was used to collect data. RESULTS: Out of the total group,
      33.6% reported that they had dieted at some time and 15.8% were presently
      dieting. The most popular definition of dieting amongst the dieters was 'eating
      less/cutting down'; however, the second most popular answer was 'eating healthy
      food' which was the most popular answer amongst the non-dieters. The most popular
      definition of healthy eating was 'increasing fruit/ veg/salads', which is similar
      to how many girls perceived dieting, i.e. eating healthy food (fruit/veg/salads).
      CONCLUSION: Establishing the actual incidence of dieting amongst adolescent girls
      is not a clear-cut issue as it can be interpreted in many different ways,
      depending on the perceptions of the individual. The results of this study showed
      that in many cases 'dieting' and 'healthy eating' were perceived in a similar
      light, concluding that the dietary intake of dieters may be similar to that of
      non-dieters with both groups being at risk from any related health problems.

PMID- 11330260
TI  - An ethnic comparison of eating attitudes and associated body image concerns in
      adolescent South African schoolgirls.
AB  - OBJECTIVE: The purpose of this study was to investigate whether differences exist
      in eating attitudes and body shape concerns amongst adolescent schoolgirls
      representing South Africa's ethnically and culturally diverse population
      currently undergoing epidemiological transition. METHOD: A questionnaire survey,
      including the Eating Attitudes Test, Body Shape Questionnaire and a Body
      Silhouette Chart, was administered to 228 South African schoolgirls (60 black, 83
      mixed race and 85 white) aged 15-18 years from five secondary schools in the
      greater Cape Town area. RESULTS: Black girls had significantly higher mean BMI
      values (24.1 (3.3)) than either white (21.9 (3.0)) or mixed race girls (22.1
      (3.7)) (P < 0.05). Controlling for differences in BMI, white subjects scored
      significantly higher on the Body Shape Questionnaire than did mixed race or black
      subjects, whereas no ethnic differences were found for Eating Attitude Test
      scores. A comparable percentage (mean = 18.8%) of black, mixed race and white
      girls had scores indicative of eating disorder pathology on the Eating Attitudes
      Test, while a higher percentage of white, compared to mixed race and black, girls
      had abnormal scores on the Body Shape Questionnaire (33%, 26% and 20%,
      respectively; P < 0.05). The ideal body size desired by white girls was
      significantly smaller than that of the mixed race or black samples.
      Dissatisfaction with present body size was significantly higher in white,
      compared to black or mixed race girls (P < 0.001). CONCLUSION: These findings
      suggest that the prevalence of abnormal eating attitudes is equally common in
      South African schoolgirls from different ethnic backgrounds. White girls exhibit
      greater body image concerns and body image dissatisfaction than mixed race or
      black individuals. These findings reinforce the notion that eating disorders are
      culture-reactive rather than culture-bound phenomena and provide insight into the
      extent of eating-related problems and body image issues in developing societies.

PMID- 11330261
TI  - Consumption of soup and nutritional intake in French adults: consequences for
      nutritional status.
AB  - AIM: The impact of soup consumption on nutrient intake and nutritional indicators
      was assessed in adults who consumed soup compared to those who did not or who
      were occasional eaters. METHODS: Data were obtained for 2,188 men and 2,849 women
      living in France and participating in the SU.VI.MAX cohort, who reported twelve
      24-h dietary records during a 2-year follow-up period (60,444 records). Subjects
      were divided into three groups: (1) those who ate soup 0-2 days or less out of 6
      days were classified as occasional or non-consumers; (2) those who consumed soup
      3-4 days out of 6 were defined as regular consumers; (3) those who consumed soup
      5-6 days out of 6 were defined as heavy consumers. RESULTS: Seven per cent of
      women and 9% of men were heavy consumers of soup. Respectively, 46 and 42% were
      regular, and 47 and 49% were occasional or non-consumers. Mean energy intake was
      lower in heavy consumers than in occasional or non-consumers, but the difference
      was statistically significant only in women. In men and women, heavy consumers of
      soup had significantly higher intakes of carbohydrates than occasional and non
      consumers (245 g J(-1) vs. 227 g J(-1) in men; 186 g J(-1) vs. 176 g J(-1) in
      women) and lower lipid intakes (97 g J(-1) vs. 102 g J(-1) in men; 80 g J(-1) vs.
      75 g J(-1) in women). Soup consumers presented lower energy intake at dinner than
      light or non-consumers. In soup consumers, breakfast and lunch contained greater
      amounts of carbohydrates, lipids and proteins, but dinner contained significantly
      smaller amounts of lipids and proteins. A higher frequency of BMI > 27 kg m(-2)
      was found in occasional and non-soup consumers; conversely a higher frequency of
      BMI between 23 and 27 kg m(-2) was found in regular consumers of soup and a
      higher frequency of BMI < 23 kg m(-2) in heavy consumers. For women, an
      association was found between occasional or non- consumers and BMI > 25 kg m(-2)
      and between heavy consumers and BMI < 22 kg m(-2). Likewise an association was
      found in men only between heavy consumption of soup and lower value of serum
      cholesterol. CONCLUSION: The present data suggest that the consumption of soups
      contributes to a balanced diet. Consumption of soup may be beneficial for a
      healthy nutritional status in the overall population.

PMID- 11330262
TI  - Reliability of a nutrition screening tool for use in elderly day hospitals.
AB  - BACKGROUND: There are a plethora of nutrition screening tools (NSTs) in use in a
      variety of clinical settings that are either unvalidated and/ or not client
      specific. There is a need for an NST for all elderly patients attending community
      day hospitals. At present such a validated tool is unavailable. AIMS: To assess
      the reliability and reproducibility of a developed NST; and to identify elderly
      patients attending day hospitals who have, or are at risk of, poor nutritional
      status. METHODS: Three day hospitals were selected and 70 admissions were
      prospectively assessed by Nursing staff and independently by a State Registered
      Dietitian (SRD) The patients' nutritional status was anthropometrically assessed
      using the NST. RESULTS: The level of agreement between the nurse and the
      dietitian for each of the levels of the NST and the overall score was either
      'good agreement' or 'very good agreement' as defined by Cohen's Kappa. Spearman's
      Rank Correlation between objective markers of assessment and the Nurse or
      Dietitian score from the NST were all statistically significant (P = 0.42). As an
      identifier of risk, the NST has low levels of sensitivity, but high levels of
      specificity. CONCLUSION: The Ayrshire NST is a reliable and valid tool which can
      be used by qualified Nursing staff to assist in screening elderly patients at
      high risk of poor nutritional status.

PMID- 11330263
TI  - The validation of a nursing nutritional assessment tool for use on acute elderly
      wards.
AB  - BACKGROUND: Elderly people are at great risk of poor nutritional status.
      Identifying those at nutritional risk is complex owing to its multifactorial
      nature and highlights the need for an easily administered nutritional screening
      tool. AIM: To test the robustness of a tool used to identify those patients who
      require further dietetic assessment. METHOD: The tool was tested on an 'acute
      elderly' ward to assess its statistical robustness, i.e. test-retest reliability,
      inter-rater reliability, internal consistency and factor structure, concurrent
      and construct validity. The research was carried out by a dietitian and two
      nurses on an overall sample of 185 consecutive admissions. RESULTS: Test-retest
      results reflect that the tool is capable of yielding consistent assessments over
      time. Inter-rater reliability results revealed that when comparisons of agreement
      between nurses and dietitians were examined there was consistent disagreement.
      Internal consistency was found to be low but the rotated factor analysis
      suggested a relationship between the items in the tool. Concurrent validity was
      exhibited with body mass index, albumin and American Nutrition Risk Index only.
      Construct validity was not sufficiently exhibited with any of the measures used.
      CONCLUSION: The tool has not demonstrated reliability as determined by the
      statistical measures and hence validity at this stage. Issues which need to be
      addressed to allow this tool to be used appropriately are discussed.

PMID- 11330264
TI  - Intolerance to an extensively hydrolysed formula mistaken for postoperative
      diarrhoea in a child with neuroblastoma.
AB  - BACKGROUND: Persistent diarrhoea has recently been reported as a common problem
      following surgical resection for advanced abdominal neuroblastoma. CASE STUDY: A
      10-month-old child, who had previously had no nutritional problems whilst
      undergoing chemotherapy treatment for a stage IV neuroblastoma, developed severe
      diarrhoea following tumour resection. He required nutritional support and was
      commenced on a continuous overnight nasogastric feed of a non-milk protein
      hydrolysate feed (MCT Pepdite 0-2, S.H.S. International Ltd, UK) His diarrhoea
      persisted and it was assumed that this was a postoperative problem which in time
      would regress. Two months later the child was admitted with a rectal prolapse,
      and a colonoscopy and biopsy suggested allergic protocolitis. The diarrhoea
      resolved rapidly on stopping the feed. CONCLUSION: Although he was never re
      challenged with the non-milk protein hydrolysate, it appears that he had a rare
      intolerance to an extensively hydrolysed protein formula which was masked by the
      assumption that his diarrhoea was a postoperative problem.

PMID- 11330265
TI  - Sex differences in weight perception and nutritional behaviour in adults with
      cystic fibrosis.
AB  - INTRODUCTION: Good nutritional status in cystic fibrosis (CF) is associated with
      improved clinical status and survival. In some conditions where dietary and
      pharmacological treatment are important (e.g. diabetes), a combination of eating
      disorders and failure of treatment compliance has been reported. Cases of eating
      disorders have been reported in CF. Societal pressures on young women to remain
      slim may compromise optimum clinical management as women are content to remain
      underweight. OBJECTIVE: To determine whether women have different perception of
      their weight than men with CF and whether this manifests in different nutritional
      behaviour. METHODS: Confidential postal questionnaire to 1870 adults with CF in
      1994 known to the Association of Cystic Fibrosis Adults (UK). Participants were
      asked their own weight and height, and their perception of their weight. Very
      underweight was defined as < 85% ideal body weight, underweight as 85-94%, normal
      weight as 95-104%, overweight as 105-114% and very overweight as 115% and over.
      RESULTS: A significantly higher proportion of women than men who are very
      underweight (29% vs. 11%) or underweight (41% vs. 15%) saw themselves as being of
      normal weight or overweight. Conversely, a significantly higher proportion of men
      than women who were normal weight (42% vs. 19%) saw themselves as underweight.
      All P-values < 0.01. A significantly higher proportion of people who perceived
      themselves to be underweight were taking oral or enteral food supplements
      compared with those who did not (77% vs. 30%, P < 0.05). Multiple logistic
      regression showed that perception of self as underweight was the strongest
      predictor of taking oral or enteral food supplements (adjusted odds ratio 2.42),
      even after adjustment for age, sex, overall severity score, body mass index, and
      seeing a dietitian in the last year. CONCLUSION: Young women with CF tend to
      overestimate their weight, and young men with CF underestimate their weight when
      compared with their actual body weight. Perception of self as underweight is
      reflected in nutritional behaviour, being a significantpredictor of taking oral
      and enteral food supplements. People working with young patients with CF should
      be aware of these sex differences in weight perception, and work with young women
      and young men with CF to achieve a realistic perception of body weight and
      realistic nutritional goals. There is a need for further research into body
      image, weight perception, eating behaviour and adherence to pancreatic enzyme
      supplementation and oral and enteral food supplementation in young patients with
      CF.

PMID- 11330266
TI  - Perception of body image as indicator of weight status in the European union.
AB  - OBJECTIVE: To identify the factors associated with an adequate perception of body
      image in relation to body weight. MATERIAL AND METHODS: An observational, cross
      sectional study was conducted in a representative sample of the European Union
      (7,155 men and 8,077 women). Body Mass Index (BMI) was grouped into four
      categories, perceived body image was assessed using the nine silhouettes drawing
      scheme. A multivariable logistic regression model for each sex was used to adjust
      for potentially confounding variables. RESULTS: Underweight men and women
      classified themselves better than other groups (92.9% of correct answers among
      men and 79.3% among women). Overall, women classified themselves better than men
      (57.6% vs. 32.7%). DISCUSSION: Perceived body image as a method of assessment for
      body weight has different validity depending on sociodemographic or attitudinal
      categories. Perceived body image as an estimate of the nutritional status has a
      limited individualized application. Thus, perhaps it could be applied as a proxy
      measure of adiposity among slim males and among slim and overweight females, but
      not among the other groups.

PMID- 11330267
TI  - How can weight control be promoted without encouraging eating disorders?

PMID- 11330268
TI  - Uses of error: Addison's disease in pregnancy.

PMID- 11330270
TI  - Smoke gets in your eyes, heart and ovaries.

PMID- 11330269
TI  - Prostate cancer screening.

PMID- 11330271
TI  - The ability to adapt to and manage change.

PMID- 11330272
TI  - Medicaid funding in Michigan: a progress report.

PMID- 11330273
TI  - Inadvertently crossing the germ line.

PMID- 11330274
TI  - Epidemiology. Intensified battle against foot and mouth appears to pay off.

PMID- 11330275
TI  - University of Rochester. Researcher sues after school spent his grant.

PMID- 11330276
TI  - X-ray crystallography. Transcription enzyme structure solved.

PMID- 11330277
TI  - Ecology. Birds weigh risk before protecting their young.

PMID- 11330279
TI  - Stem cells. NIH pulls plug on ethics review.

PMID- 11330278
TI  - Microarrays. Data standards on the horizon.

PMID- 11330280
TI  - Japan. Women academics propose steps to equity.

PMID- 11330281
TI  - Workforce diversity. NSF makes the BEST of a good idea.

PMID- 11330283
TI  - Quantum computing. Souped-up software gets a virtual test.

PMID- 11330282
TI  - Behavioral ecology. Elephant matriarchs tell friend from foe.

PMID- 11330284
TI  - Nuclear radiation. Living in the shadow of Chornobyl.

PMID- 11330285
TI  - Nuclear radiation. Genetic studies of wildlife in the hot zone reach different
      conclusions.

PMID- 11330286
TI  - Nuclear radiation. Dealing with a slumbering hulk.

PMID- 11330287
TI  - Nuclear radiation. Ordeals of a dissenter.

PMID- 11330288
TI  - Nuclear radiation. Rewards of a volunteer.

PMID- 11330289
TI  - Cell biology. Do centrosome abnormalities lead to cancer?

PMID- 11330290
TI  - Developmental biology. The hottest stem cells are also the toughest.

PMID- 11330291
TI  - Proposed research budget a   starting point.

PMID- 11330292
TI  - Marine iguanas oiled in the   Galapagos.

PMID- 11330293
TI  - Removing CO2 from Lake   Nyos in Cameroon.

PMID- 11330294
TI  - Mutation in embryonic stem   cells.

PMID- 11330295
TI  - More about duikers in   ancient Egypt.

PMID- 11330296
TI  - Biomedicine. The NASA-NCI collaboration on biomolecular sensors.

PMID- 11330298
TI  - Bose-Einstein condensation. A new trick of the trade.

PMID- 11330297
TI  - Photosynthesis. Splitting water.

PMID- 11330299
TI  - Molecular biology. Invading the genetic code.

PMID- 11330300
TI  - Tech.Sight. Sequencing genomes and beyond.

PMID- 11330301
TI  - Disappearing stem cells, disappearing science.

PMID- 11330302
TI  - Drug patents. Universities, NIH hear the price isn't right on essential drugs.

PMID- 11330303
TI  - AIDS origins. Disputed AIDS theory dies its final death.

PMID- 11330305
TI  - Astrophysics. Images and model catch planets as they form.

PMID- 11330304
TI  - Developmental biology. Stem cells are coaxed to produce insulin.

PMID- 11330306
TI  - Astronomy. Critics of 'halo matter' outrace the presses.

PMID- 11330308
TI  - Japan. Reforms could threaten facility spending hike.

PMID- 11330307
TI  - Middle East. Two pledges boost SESAME project.

PMID- 11330309
TI  - Taste research. New gene may be key to sweet tooth.

PMID- 11330310
TI  - Archaeology. The first urban center in the Americas.

PMID- 11330311
TI  - Neuroscience. How the brain understands music.

PMID- 11330312
TI  - The mitochondrion: is it central to apoptosis?

PMID- 11330313
TI  - American Association of Physical Anthropologists meeting. Studying humans--and
      their cousins and parasites.

PMID- 11330314
TI  - German Research Minister. Bulmahn is bullish on science reforms.

PMID- 11330315
TI  - Archaeology. New trips through the back alleys of agriculture.

PMID- 11330316
TI  - GM crops and patterns of   pesticide use.

PMID- 11330317
TI  - Risk assessment data for   GM crops.

PMID- 11330318
TI  - Conflicts of interest.

PMID- 11330319
TI  - Human cloning--not if, but when.

PMID- 11330320
TI  - Human cloning--not if, but when.

PMID- 11330321
TI  - Environment and development. Sustainability science.

PMID- 11330323
TI  - Laser chemistry. Keeping reactions under quantum control.

PMID- 11330322
TI  - Microbiology. Fighting anthrax with a mutant toxin.

PMID- 11330324
TI  - Nanotubes. Burn and interrogate.

PMID- 11330325
TI  - Bioinorganic chemistry. Oxygenase pathways: oxo, peroxo, and superoxo.

PMID- 11330326
TI  - RNA structure. Pulling on hair(pins).

PMID- 11330327
TI  - Myriad ways to reconstruct past climate.

PMID- 11330328
TI  - The tropics return to the climate system.

PMID- 11330329
TI  - High concentrations of oxytocin cause vasoconstriction by activating vasopressin
      V1A receptors in the isolated perfused rat kidney.
AB  - The aim of this study was to evaluate the renal vascular effects of oxytocin in
      Sprague-Dawley rats and in Brattleboro heterozygous or homozygous rats, the
      latter being genetically deficient in vasopressin synthesis. Studies were
      performed in vitro, in the isolated kidney perfused in an open circuit with a
      Tyrode's solution. Oxytocin induced a concentration-dependent renal
      vasoconstriction in Sprague-Dawley rats, at rather high concentrations
      (EC50=170+/-39 nM, mean +/- SEM, n=6) with a maximum response amounting to 44% of
      that elicited by vasopressin (increase in renal vascular resistance: 11.5+/-0.9
      mmHg min ml(-1) vs. 26.2+/-2.2 mmHg min ml(-1)). Oxytocin-evoked renal
      vasoconstriction was abolished by SR 49059, a selective vasopressin V1A receptor
      antagonist (10 nM), but not by d(CH2)5[Tyr(Me)2,Thr4,Orn8,Tyr-(NH2)9] vasotocin,
      an oxytocin receptor antagonist (10 nM). In the presence of SR 49059, oxytocin
      did not induce renal vasorelaxation. Oxytocin induced renal vasoconstriction in
      Brattleboro homozygotes and heterozygotes (EC50=59+/-12 nM and 262+/-110 nM;
      Emax=7.8+/-1.1 mmHg min ml(-1) and 6.9+/-0.4 mmHg min ml(-1), n=5 respectively)
      with characteristics similar as observed in Sprague-Dawley rats concerning
      partial agonist activity, low potency and antagonism by SR 49059. Responsiveness
      to vasopressin did not differ in Brattleboro homozygotes and heterozygotes (EC50
      approximately 0.25 nM) and was similar as we reported in Sprague-Dawley rats.
      These findings indicate that high concentrations of oxytocin induce renal
      vasoconstriction in the rat by activating vasopressin V1A receptors. The low
      agonist activity makes it unlikely that oxytocin can substitute functionally for
      vasopressin at the renal vascular V1A receptor in Brattleboro homozygous rats
      which are deficient in endogenous vasopressin.

PMID- 11330330
TI  - Dopamine receptors in human platelets.
AB  - The expression of dopamine receptors by human platelets was investigated by
      Western blot analysis and immunocytochemical techniques using antibodies raised
      against dopamine D1-D5 receptor protein. The influence of dopamine D1-like and D2
      like receptor agonists on adrenaline-induced platelet aggregation was also
      investigated. Western blot analysis revealed that platelet membranes bind anti
      dopamine D3 or D5 receptor protein antibodies, but not anti-D1, D2 or D4 receptor
      protein antibodies. Cytospin centrifuged human platelets exposed to anti-dopamine
      D3 or D5 receptor protein antibodies developed a specific immune staining,
      whereas no positive staining was noticeable in platelets exposed to other
      antibodies tested. Both the D1-like receptor agonist 1-phenyl2,3,4,5-tetrahydro
      (1H)-3-benzazepine-7,8-diol hydrochloride (SKF 38393) and the D2-like receptor
      agonist 7-hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OH-DPAT) dose-dependently
      inhibited adrenaline-induced platelet aggregation. These effects were decreased
      respectively by the D-like and D2-like receptor antagonists R(+)-2,3,4,5
      tetrahydro-3-methyl-5-phenyl-1H-3-benzazepin-7-ol hydrochloride (SCH 23390) and (
      )sulpiride. The above findings indicate that human platelets express dopamine D3
      and D5 receptors probably involved in the regulation of platelet function.

PMID- 11330331
TI  - Different effects of endothelin-1 on calcium and potassium currents in canine
      ventricular cells.
AB  - Effects of endothelin-1 (ET-1) on the L-type calcium current (ICa) and delayed
      rectifier potassium current (IK) were studied in isolated canine ventricular
      cardiomyocytes using the whole-cell configuration of the patch-clamp technique.
      ET-1 (8 nM) was applied in three experimental arrangements: untreated cells, in
      the presence of 50 nM isoproterenol, and in the presence of 250 microM 8-bromo
      cAMP. In untreated cells, ET-1 significantly decreased the peak amplitude of ICa
      by 32.3+/-4.8% at +5 mV (P<0.05) without changing activation or inactivation
      characteristics of ICa. ET-1 had no effect on the amplitude of IK, Ito (transient
      outward current) or IK1 (inward rectifier K current) in untreated cells; however,
      the time course of recovery from inactivation of Ito was significantly increased
      by ET-1 (from 26.5+/-4.6 ms to 59.5+/- 1.8 ms, P < 0.05). Amplitude and time
      course of intracellular calcium transients, recorded in voltage-clamped cells
      previously loaded with the fluorescent calcium indicator dye Fura-2, were not
      affected by ET-1. ET-1 had no effect on force of contraction in canine
      ventricular trabeculae. Isoproterenol increased the amplitude of ICa to 263+/-29%
      of control. ET-1 reduced ICa also in isoproterenol-treated cells by 17.8+/-2%
      (P<0.05); this inhibition was significantly less than obtained in untreated
      cells. IK was increased by isoproterenol to 213+/-18% of control. This effect of
      isoproterenol on IK was reduced by 31.8+/-4.8% if the cells were pretreated with
      ET-1. Similarly, in isoproterenol-treated cells ET-1 decreased IK by 16.2+/-1.5%
      (P<0.05). Maximal activation of protein kinase A (PKA) was achieved by
      application of 8-bromo-cAMP in the pipette solution. In the presence of 8-bromo
      cAMP ET-1 failed to alter ICa or IK It was concluded that differences in effects
      of ET-1 on ICa and IK may be related to differences in cAMP sensitivity of the
      currents.

PMID- 11330332
TI  - Pindolol antagonises G-protein activation at both pre- and postsynaptic serotonin
      5-HT1A receptors: a.
AB  - The arylalkylamine, pindolol, may potentiate the clinical actions of
      antidepressant agents. Although it is thought to act via blockade of 5-HT1A
      autoreceptors, its efficacy at these sites remains controversial. Herein, we
      evaluated the actions of pindolol at 5-HT1A autoreceptors and specific
      populations of postsynaptic 5-HT1A receptors employing [35S]GTPgammaS
      autoradiography, a measure of receptor-mediated G-protein activation. Both 8-OH
      DPAT (1 microM) and 5-HT (10 microM) elicited a pronounced increase in [35S]GTPyS
      binding in the dorsal raphe nucleus, which contains serotonergic cell bodies
      bearing 5-HT1A autoreceptors. Pindolol abolished their actions. In the dentate
      gyrus, lateral septum and entorhinal cortex, structures enriched in postsynaptic
      5-HT1A receptors, 8-OH-DPAT (1 microM) and 5-HT (10 microM) also elicited a
      marked increase in [35S]GTPgammaS binding which was likewise blocked by pindolol.
      The antagonism of 5-HT-induced [35S]GTPgammaS labelling in the dentate gyrus was
      shown to be concentration-dependent, yielding a pIC50 of 5.82. Pindolol did not,
      itself, affect [35S]GTPgammaS binding in any brain region examined. In
      conclusion, these data suggest that, as characterised by [35S]GTPgammaS
      autoradiography, and compared with 5-HT and 8-OH-DPAT, pindolol possesses low
      efficacy at both pre- and postsynaptic 5-HT1A receptors.

PMID- 11330333
TI  - Subcutaneous formalin enhances outflow of met-enkephalin- and cholecystokinin
      like materials in the rat nucleus accumbens.
AB  - Using the microdialysis technique, the present study investigated the effects of
      a noxious stimulation on the extracellular levels of met-enkephalin and (sulfated
      octapeptide) cholecystokinin-like materials in the nucleus accumbens of freely
      moving rats. Injection of 50 microl of 5% formalin into the forepaw produced pain
      related behaviours associated with an immediate and sustained (for approximately
      2 h) increase (+27%) in the outflow of met-enkephalin-like material within the
      nucleus accumbens. This treatment also progressively enhanced the local outflow
      of cholecystokinin-like material that reached 200%-250% of the basal level at the
      end of the experiment, i.e. 4.5 h after formalin administration. Because naloxone
      (1.5 mg/kg i.p., 10 min prior to formalin injection) prevented the latter effect,
      it can be inferred that noxious stimulation-induced activation of
      cholecystokininergic neurotransmission in the nucleus accumbens probably resulted
      from the preceding activation of opioidergic systems. These data suggest that the
      nucleus accumbens may be another structure where interactions between opioids and
      cholecystokinin play a key role in the control of pain-processing mechanisms.

PMID- 11330334
TI  - On the mechanism of the protective effects of nitroglycerin and nicorandil in
      cardiac anaphylaxis.
AB  - Previous investigations have shown that nitric oxide donors and nicorandil can
      suppress allergic reaction. In the present study, the protective effects of
      nitroglycerin and nicorandil on cardiac anaphylaxis were examined. Presensitized
      guinea-pig hearts challenged with specific antigen caused a marked decrease in
      coronary flow (CF), left ventricular pressure (LVP) and its derivatives (+/
      dp/dtmax), increase in heart rate, and prolongation of P-R interval.
      Nitroglycerin (300 nM) or nicorandil (100 microM) markedly increased the content
      of calcitonin gene-related peptide (CGRP) concomitant with a significant
      improvement of the cardiac dysfunction and alleviation of the extension of P-R
      interval. Nicorandil at a concentration of 100 microM also inhibited the sinus
      tachycardia and histamine release. The protection afforded by nitroglycerin was
      abolished by glibenclamide, a blocker of ATP-sensitive potassium channels, or by
      CGRP8-37, the selective CGRP receptor antagonist, or by pretreatment with
      capsaicin, which depletes endogenous CGRP. The inhibitory effect of nicorandil on
      cardiac anaphylaxis was abolished only by glibenclamide but not by pretreatment
      with capsaicin. These results suggest that nitroglycerin and nicorandil possess a
      protection of cardiac anaphylactic injury. The present study also suggests that
      the protective effect of nitroglycerin may be related to stimulation of CGRP
      release and opening the KATP channel, and that the effect of nicorandil is mainly
      due to the activation of the KATP channel.

PMID- 11330335
TI  - [3H]acetycholine release in rat striatal slices is not subject to dopamine
      heteroreceptor supersensitivity 30 months after 6-hydroxydopamine lesion of the
      substantia nigra.
AB  - Using the rat model of Parkinson's disease described by Ungerstedt the release of
      [3H]acetylcholine ([3H]ACh) in the caudatoputamen was investigated to assess
      possible long-term effects of unilateral dopaminergic denervation on the
      modulation of cholinergic interneurons. This seemed of interest since rats with 6
      hydroxydopamine (6-OHDA) lesions of the left substantia nigra showed an increase
      in the behavioural susceptibility to small doses of dopamine (DA) D2 receptor
      agonists 30 months after the lesion. Electrical field stimulation with 3 Hz
      elicited release of [3H]ACh in slices of both the lesioned and the intact
      striatum. The DA reuptake blocker nomifensine was ineffective on the lesioned
      side but diminished the release of [3H]ACh in the intact striatum. This
      inhibition was reversed by the D2 receptor antagonist domperidone and hence
      probably due to the effect of endogenously released DA. Single electrical pulses
      at 0.05 Hz, which neither induced autoinhibition of [3H]ACh release nor
      heteroinhibition by endogenous DA, elicited a higher release of [3H]ACh on the
      intact side. Under this stimulation paradigm activation of the D2 heteroreceptor
      with quinpirole depressed the release of [3H]ACh to a similar extent on both
      sides, irrespective of the absence or presence of the competitive NMDA receptor
      antagonist D-CPPene. Also blockade of the NMDA receptor channel by dizocilpine,
      or of AMPA receptors by NBQX, was ineffective on either side. The NMDA-evoked
      release of [3H]ACh was higher on the lesioned side. It was equally depressed by
      quinpirole and by ethanol on both sides. Thus, single electrical pulses and NMDA
      stimulation per se had opposite effects on the lesioned and the intact side,
      whereas the modulation of release was similar. Since the lesioned striata were
      considerably smaller, measurements of mRNA levels of choline acetyltransferase
      (ChAT) were used to assess the density of cholinergic interneurons and their
      content of ChAT mRNA. This analysis did not reveal any side difference. In
      conclusion, the function of D2 heteroreceptors on, and the density and ChAT mRNA
      content of, cholinergic interneurons are not or no longer altered after long-term
      DA denervation. Most probably, cholinergic interneurons are not involved in the
      increased behavioural susceptibility of 6-OHDA-lesioned rats to DA agonists.

PMID- 11330336
TI  - Effects of repeated systemic administration of d-Fenfluramine on serotonin and
      glutamate release in rat ventral hippocampus: comparison with methamphetamine
      using in vivo microdialysis.
AB  - We compared the effects of three systemic injections of various doses of d
      Fenfluramine, an indirect serotonergic agonist (1.3, 5 or 10 mg/kg), to those of
      a known neurotoxin, methamphetamine (METH, at a 7.5 mg/kg dose), given i.p. at 2
      h intervals, simultaneously on extracellular levels of glutamate [Gluext] and 5
      HT [5-HText] in the ventral hippocampus (VHPC) using in vivo microdialysis in
      conscious rats. METH markedly increased both [Gluext] (+77% over the control
      value in saline-treated rats) and [5-HText] (around +250% over controls) in the
      VHPC. d-Fenfluramine, at all the doses studied, induced gradual increases of [5
      HText] in the VHPC (between +125% and +417% over control values), but did not
      modify [Gluext]. These data highlight marked in vivo differences between METH and
      d-Fenfluramine in their effects on extracellular levels of 5-HT and Glu in the
      rat ventral hippocampus following their repeated systemic administration.

PMID- 11330337
TI  - Differential inhibition of [3H]-oxotremorine-M and [3H]-quinuclinidyl benzilate
      binding to muscarinic receptors in rat brain membranes with acetylcholinesterase
      inhibitors.
AB  - The potential interaction of acetylcholinesterase inhibitors with cholinergic
      receptors may play a significant role in the therapeutic and/or side-effects
      associated with this class of compound. In the present study, the capacity of
      acetylcholinesterase inhibitors to interact with muscarinic receptors was
      assessed by their ability to displace both [3H]-oxotremorine-M and [3H]
      quinuclinidyl benzilate binding in rat brain membranes. The [3H]-quinuclinidyl
      benzilate/[3H]-oxotremorine-M affinity ratios permitted predictions to be made of
      either the antagonist or agonist properties of the different compounds. A series
      of compounds, representative of the principal classes of acetylcholinesterase
      inhibitors, displaced [3H]-oxotremorine-M binding with high-to-moderate potency
      (ambenonium>neostigmine=pyridostigmine=tacrine>physostigmine>
      edrophonium=galanthamine>desoxypeganine) whereas only ambenonium and tacrine
      displaced [3H]-quinuclinidyl benzilate binding. Inhibitors such as
      desoxypeganine, parathion and gramine demonstrated negligible inhibition of the
      binding of both radioligands. Scatchard plots constructed from the inhibition of
      [3H]-oxotremorine-M binding in the absence and presence of different inhibitors
      showed an unaltered Bmax and a reduced affinity constant, indicative of potential
      competitive or allosteric mechanisms. The capacity of acetylcholinesterase
      inhibitors, with the exception of tacrine and ambenonium, to displace bound [3H]
      oxotremorine-M in preference to [3H]quinuclinidyl benzilate predicts that the
      former compounds could act as potential agonists at muscarinic receptors.
      Moreover, the rank order for potency in inhibiting acetylcholinesterase
      (ambenonium>neostigmine=physostigmine
      =tacrine>pyridostigmine=edrophonium=galanthamine
      >desoxypeganine>parathion>gramine) indicated that the most effective inhibitors
      of acetylcholinesterase also displaced [3H]-oxotremorine-M to the greatest
      extent. The capacity of these inhibitors to displace [3H]-oxotremorine-M binding
      preclude their utilisation for the prevention of acetylcholine catabolism in rat
      brain membranes, the latter being required to estimate the binding of
      acetylcholine to [3H]-oxotremorine-M-labelled muscarinic receptors. However,
      fasciculin-2, a potent peptide inhibitor of acetylcholinesterase (IC50 24 nM),
      did prevent catabolism of acetylcholine in rat brain membranes with an atypical
      inhibition isotherm of [3H]-oxotremorine-M binding, thus permitting an estimation
      of the "global affinity" of acetylcholine (Ki 85 nM) for [3H]-oxotremorine-M
      labelled muscarinic receptors in rat brain.

PMID- 11330338
TI  - ET-receptor function in relation to blood pressure in spontaneously hypertensive
      and aortic-banded rats.
AB  - Endothelin-1 (ET-1), a potent endogenous vasoconstrictor, has been proposed to
      play a pathophysiologic role in hypertension. The aim of this study was to find
      out whether changes in ET-receptor function are cause or consequence of blood
      pressure elevation in hypertension. For this purpose, we assessed ET-receptor
      function [as ET-1-induced [3H]inositol phosphate (IP) accumulation] in slices of
      left ventricle and renal cortex and in rings of thoracic and abdominal aorta from
      spontaneously hypertensive rats (SHR) at the age of 8 weeks (i.e. developing
      hypertension), 12 and 24 weeks (established hypertension) vs. normotensive age
      matched Wistar-Kyoto (WKY) rats, and from supra-renal aortic-banded (AOB) rats at
      the age of 8, 12 and 24 weeks (i.e. 4, 8 and 20 weeks after AOB) vs. sham
      operated (SOP) age-matched WKY rats. In the SHR with established hypertension ET
      1-induced IP formation was altered in all tissues investigated: it was
      significantly increased vs. WKY rats in left ventricle, and significantly
      decreased in renal and aortic tissues. Similarly, in AOB rats at all ages ET-1
      induced IP formation was changed in those tissues that were under pressure load
      [heart (increase) and thoracic aorta (decrease)] vs. SOP rats, whereas in those
      tissues not under pressure load (kidney and abdominal aorta) ET-1-induced IP
      formation was not different between AOB and SOP rats. Moreover, in 8-week-old SHR
      (where hypertension is not yet established) ET-1-induced IP formation was not
      significantly different compared to WKY rats (with the exception of thoracic
      aorta). We conclude that, at least in SHR and AOB rats, changes in ET-1
      signalling are secondary to the elevation in blood pressure.

PMID- 11330339
TI  - Sustained administration of the antidepressant venlafaxine in rats:
      pharmacokinetic and pharmacodynamic findings.
AB  - Rats were administered venlafaxine (10 mg/kg per day) for 14 days by using
      subcutaneously implanted osmotic minipumps. The present study assessed the
      distribution of VEN in different compartments, whether the VEN concentration in
      the compartments correlated, the effect of VEN on dialysate monoamine levels and
      on the spontaneous open-field behavior, and possible relations between the
      pharmacokinetic and pharmacodynamic parameters. The venlafaxine level in serum
      after sustained treatment was about 25% of the concentration in brain parenchyma
      and much higher than in brain dialysate. There was a clear correlation between
      venlafaxine concentrations in blood and brain compartments. The sustained
      venlafaxine challenge resulted in higher neocortical concentration of serotonin
      and noradrenaline, lower 5-hydroxyindole-3-acetic acid levels and increased
      locomotor activity in the central part of the test arena as compared to controls.
      No correlations were found between the venlafaxine concentration and brain
      monoamine parameters or the open-field behaviors. We conclude that, although
      species differences in pharmacokinetic properties for venlafaxine between rat and
      man exist, the pharmacokinetic correlations found after sustained treatment add
      information to the in vivo nature of the drug. Also, more studies like the
      present need to be performed to find the pharmacokinetic/pharmacodynamic
      interrelations for drugs like VEN.

PMID- 11330340
TI  - Evidence for a short form of RGS3 preferentially expressed in the human heart.
AB  - RGS proteins (regulators of G protein signalling) negatively regulate G protein
      function as GTPase-activating proteins (GAP) for G protein alpha-subunits. The
      existence of mRNAs of different size for some of the RGS proteins, e.g. RGS3,
      suggests that these proteins may exist in isoforms due to alternative splicing.
      We therefore investigated RGS3 mRNA and protein expression in different human
      tissues. Ribonuclease protection assays and Northern blot analysis showed two
      specific mRNAs for RGS3 (RGS3L, RGS3S) in human myocardium, suggesting an
      additional, N-terminally truncated form of approximately 168 aa. When expressed
      as a recombinant protein RGS3S was recognized at approximately 23 kDa by an
      antipeptide antiserum originally raised against an RGS2 sequence. In membranes of
      human tissues this antiserum detected specific signals for RGS3L (approximately
      70 kDa), RGS2 (approximately 30 kDa) and a 25-kDa protein, most likely RGS3S.
      Both RGS3S mRNA and the 25 kDa protein were abundant in human heart, whereas
      expression in liver, brain and myometrium was much weaker. To characterize RGS3S
      functionally, single turnover GTPase, adenylyl cyclase (AC) and phospholipase C
      (PLC) activities were determined. Both recombinant RGS3S and RGS16 increased Pi
      release from Galphai1 by about 150% and increased GTP- and GTP plus isoprenaline
      stimulated AC activity by 20-30% in human left ventricular myocardial membranes.
      Additionally, both RGS proteins reduced basal and endothelin-stimulated PLC
      activity in these membranes by about 40%. We conclude that an additional
      truncated form of RGS3 is expressed in the human heart. As described for the full
      length protein, RGS3S negatively regulates the activity of Gi/o- and Gq-, but not
      Gs-subfamily members.

PMID- 11330341
TI  - Evidence that ranolazine behaves as a weak beta1- and beta2-adrenoceptor
      antagonist in the rat [correction of cat] cardiovascular system.
AB  - The clinical anti-anginal effectiveness of ranolazine is currently being
      evaluated. However, the mechanism of its anti-ischaemic action is still unclear.
      The aim of this work was to establish whether ranolazine exerts functional beta
      adrenoceptor antagonist activity in the rat cardiovascular system. Radioligand
      binding studies were performed in rat hearts and guinea-pig lungs for beta1- and
      beta2-adrenoceptor affinity, respectively. Ranolazine had micromolar affinity for
      both beta,- and beta2-adrenoceptors (pKi5.8 and 6.3, respectively). Developed
      tension was measured in isolated rat left atria (electrically driven at 4 Hz) and
      cumulative concentration/response curves to (+/-)isoprenaline (0.01-1,000 nM)
      constructed. Ranolazine (0.32-10 microM) surmountably but weakly antagonised
      isoprenaline-induced positive inotropic responses, with an apparent pA2 of 5.85
      (5.69-6.00) and a slope of -0.74 (-0.70 to -0.77). In bivagotomised, atropinised
      pithed rats, ranolazine per se evoked marked bradycardia at doses above 10 mg/kg
      i.v. (maximum variation at 80 mg/kg -125+/-15 bpm, n=6, P<0.001) by a mechanism
      apparently unrelated to blockade of beta1- or beta2-adrenoceptors. Cumulative
      incremental doses of (+/-)isoprenaline (0.63 ng/kg to 0.16 mg/kg i.v.)
      administered to pithed rats induced concomitant depressor and chronotropic
      responses. Animals received either vehicle (saline 0.9% i.v., n=12), atenolol
      (0.04-2.5 mg/kg i.v., n=6 per dose), ICI 118551 (0.01-0.63 mg/kg i.v., n=6 or 7
      per dose), (+/-)propranolol (0.01-0.63 mg/kg i.v., n=6 per dose) or ranolazine
      (2.5-80 mg/kg i.v., n=6 or 7 per dose) 10 min prior to isoprenaline. Ranolazine
      dose-dependently and competitively antagonised isoprenaline-induced decreases in
      diastolic arterial pressure (DAP, dose ratio 12.2 with 80 mg/kg ranolazine) and
      increases in heart rate (HR, dose ratio 20.3 with 80 mg/kg ranolazine).
      Collectively, these results demonstrate that ranolazine behaves as a weak beta1-
      and beta2-adrenoceptor antagonist in the rat cardiovascular system.

PMID- 11330342
TI  - Blocking effects of the antiarrhythmic drug propafenone on the HERG potassium
      channel.
AB  - Propafenone has been shown to affect the delayed-rectifier potassium currents in
      cardiomyocytes of different animal models. In this study we investigated effects
      and mechanisms of action of propafenone on HERG potassium channels in oocytes of
      Xenopus laevis with the two-electrode voltage-clamp technique. Propafenone
      decreased the currents during voltage steps and the tail currents. The block was
      voltage-dependent and increased with positive going potentials (from 18% block of
      tail current amplitude at -40 mV to 69% at +40 mV with 100 micromol/l
      propafenone). The voltage dependence of block could be fitted with the sum of a
      monoexponential and a linear function. The fractional electrical distance was
      estimated to be delta=0.20. The block of current during the voltage step
      increased with time starting from a level of 83% of the control current.
      Propafenone accelerated the increase of current during the voltage step as well
      as the decay of tail currents (time constants of monoexponential fits decreased
      by 65% for the currents during the voltage step and by 37% for the tail currents
      with 100 micromol/l propafenone). The threshold concentration of propafenone
      effect was around 1 micromol/l and the concentration of half-maximal block (IC50)
      ranged between 13 micromol/l and 15 micromol/l for both current components. With
      high extracellular potassium concentrations, the IC50 value rose to 80 degrees
      mol/l. Acidification of the extracellular solution to pH 6.0 increased the IC50
      value to 123 micromol/l, alkalization to pH 8.0 reduced it to 10 micromol/l and
      coexpression of the beta-subunit minK had no statistically significant effect on
      the concentration dependence. In conclusion, propafenone has been found to block
      HERG potassium channels. The data suggest that propafenone affects the channels
      in the open state and give some hints for an intracellular site of action.

PMID- 11330344
TI  - Detection of squalene in alpha-fetoprotein and fetal serum albumin from bovine.
AB  - Alpha-fetoprotein and fetal serum albumin have been simultaneously purified from
      fetal bovine serum by mild procedures utilizing ammonium sulfate, hydrophobic
      interaction, immobilized metal (nickel) affinity chromatography, and isoelectric
      focusing. The lipidic extract from each protein was analyzed by gas
      chromatography and the peak appearing just after the arachidonic acid was
      identified as squalene by gas chromatography-mass spectrometry. This isoprenoid
      was not detected formerly in these proteins from human, rat, bovine, and pig.
      Until recently, in the analysis of the fatty acid composition of the alpha
      fetoprotein and serum albumin from mammals, a peak has been assigned in the last
      part of the chromatographic profile, after arachidonic acid, to docosahexaenoic
      acid. In the present work, it was found that the peak corresponds to squalene
      instead of docosahexaenoic acid. Furthermore, we conclude that bovine alpha
      fetoprotein and fetal serum albumin carry squalene, but not docosahexaenoic acid.
      These results agree with others obtained analyzing the same proteins from chick
      embryo.

PMID- 11330343
TI  - Biochemical characterization and N-terminal sequences of two new trypsin
      inhibitors from Copaifera langsdorffii seeds.
AB  - Two new trypsin inhibitors, TDI-I and TDI-II, were purified from the seeds of the
      native Brazilian tree Copaifera langsdorffii (Caesalpinoideae, Leguminosae). The
      purification procedure involved ammonium sulfate fractionation, ion-exchange
      chromatography on DEAE-Sepharose, affinity chromatography on trypsin-Sepharose,
      and reversed-phase (RP) HPLC. RP-HPLC yielded two forms (TDI-I and TDI-II), as
      confirmed by isoelectric focusing, with pI values between 7.0 and 8.1. The
      molecular mass of the TDI forms was 24 kDa based on FPLC gel filtration on
      Superdex 75. Under reducing conditions in tricine SDS-PAGE the molecular masses
      of TDI-I and TDI-II were 12 and 10 kDa, respectively. The Ki values were 1.1 and
      1.2 nM for TDI-I and TDI-II, respectively, and there was no inhibitory effect on
      chymotrypsin. Amino acid analysis revealed high levels of aspartic acid, glutamic
      acid, serine, glycine, proline, and lysine but low levels of methionine and
      aromatic amino acids in both inhibitors; the calculated molecular masses were
      11,456 and 10,008 for TDI-I and II, respectively. Based on the N-terminal
      sequences of TDI-I and TDI-II, TDI-I belongs to the Kunitz family of trypsin
      inhibitors, whereas TDI-II showed no homology to any other protein. This
      observation suggests that TDI-II belongs to a new inhibitor subclass of low
      molecular mass proteins in the subfamily Caesalpinoideae.

PMID- 11330345
TI  - Synthesis of esculentin-1 antibacterial peptide fragments on 1,4-butanediol
      dimethacrylate cross-linked polystyrene support.
AB  - Peptide segments corresponding to antibacterial esculentin-1 (1-15), (3344), (9
      27), and their modified forms were synthesized on 1,4-butanediol dimethacrylate
      cross-linked polystyrene (PS-BDODMA) support. Hydroxymethyl and aminomethyl 2% PS
      BDODMA supports were used for the synthesis. The HMPB linker was appended to the
      aminomethyl resin using HBTU in presence of HOBt and the first amino acid was
      incorporated using MSNT. The conventional Fmoc synthetic protocol was used for
      the synthesis of peptides. The peptides were cleaved from the support using TFA.
      The peptides were purified by HPLC, and characterized by amino acid analysis and
      MALDI TOF MS. The secondary structures of the peptides were revealed by CD
      measurements. The synthesis of these peptides illustrates the utility of the new
      support for the synthesis of long-chain bioactive peptides. The synthetic
      peptides were tested for antimicrobial activity against Escherichia coli Mos
      blue, E. coli 2, Bacillus brevis, B. megaterium, Pseudomonas HTL, and Vibrio
      mimicus. The antibacterial activity of the peptides was explained on the basis of
      the helicity and charged nature of the sequences.

PMID- 11330346
TI  - The effect of calcium (II) on the binding of anticoagulation factor I with
      activated coagulation factor X.
AB  - Anticoagulation factor I (ACF I) from the venom of Agkistrodon acutus forms a 1:1
      complex with activated coagulation factor X (FXa) in a Ca2+-dependent fashion and
      thereby prolongs the clotting time. In the present study, the dependence of the
      binding of ACF I with FXa on the concentration of Ca2+ ions was quantitatively
      analyzed by HPLC, and the result showed that the maximal binding of ACF I to FXa
      occurred at concentration of Ca2+ ions of about 1 mM. The binding of Ca2+ ions to
      ACF I was investigated by equilibrium dialysis and two Ca2+-binding sites with
      different affinities were identified. At pH 7.6, the apparent association
      constants K1 and K2 for these two sites were (1.8 +/- 0.5) x 10(5) and (2.7 +/-
      0.6) x 10(4) M(-1) (mean +/- SE, n = 4), respectively. It was evident from the
      observation of Ca2+-induced changes in the intrinsic fluorescence of ACF I that
      ACF I underwent a conformational change upon binding of Ca2+ ions. The occupation
      of both Ca2+-binding sites in ACF I required a concentration of Ca2+ ions of
      about 1 mM, which is equal to the effective concentration of Ca2+ ions required
      both for maximal binding of ACF I to FXa and for the maximal enhancement of
      emission fluorescence of ACF I. It could be deduced from these results that the
      occupation of both Ca2+-binding sites in ACF I with Ca2+ ions and subsequent
      conformational rearrangement might be essential for the binding of ACF I to FXa.

PMID- 11330347
TI  - Association and activation of fructose 1,6-bisphosphase during unfolding and
      refolding: spectroscopic and enzymatic studies.
AB  - Fructose 1,6-biphosphase is a well-characterized oligomer enzyme, and many
      effectors allosterically control its activity. In this report, we compared the
      activity, allosteric properties, and conformational changes in its denaturant
      induced unfolding processes. In addition, a trpytophan residue has been
      introduced into the interface between the C1 and C2 subunits to investigate
      conformational changes during unfolding. Results show that the denaturation
      curves of WT FruP2ase detected by various methods do not agree, and the
      dissociation occurs first with a monomeric form existing around 0.4 M GdmCl as
      shown by gel filtration. The dissociation of all mutants is accompanied by
      changes in fluorescence intensity. The results suggest that the unfolding of
      FruP2ase is a complicated, multiphase process. The activation of FruP2ase by
      GdmCl at low concentrations can be interpreted as a consequence of the effect of
      monovalent cation. In the refolding experiments, it is found that Mg2+ is not
      only essential for enzyme activity, but also can assist the enzyme in refolding
      and association by preventing the formation of aggregates.

PMID- 11330348
TI  - Kinetic and structural properties of two isoforms of trypsin isolated from the
      viscera of Japanese anchovy, Engraulis japonicus.
AB  - Two isoforms of anchovy trypsin (aT-I and aT-II) were purified from the visceral
      extracts by (NH4)2SO4 fractionation followed by affinity chromatography, gel
      filtration, and ion-exchange chromatography. The homogeneity of the purified
      preparation was evidenced by both native- and SDS-PAGE, and further by gelatin
      zymography. Identities of aT-I and aT-II as trypsins were established by N
      terminal amino acid sequencing, which matched exactly to the corresponding
      stretches of their respective amino acid sequences obtained by molecular cloning
      [Ahsan et al. (2000), Marine Biotechnol., in press]. Both isoforms were
      completely inhibited by serine protease inhibitors as well as by specific trypsin
      inhibitors. The purified anchovy trypsins showed considerably higher catalytic
      efficiencies (kcat/Km) than bovine trypsin as measured toward benzoyl-arginine p
      nitroanilide (BAPA) and benzoyl-arginine ethyl ester (BAEE) at 25 degrees C; in
      particular, aT-II was 35 times more efficient than its mammalian counterpart
      against BAPA. This was due mainly to a dramatic decrease of Km values for anchovy
      trypsins, which are indicative of an evolutionary response toward increased
      substrate binding at suboptimal temperatures in the marine environment.

PMID- 11330349
TI  - Crystal structure of the complex of concanavalin A and tripeptide.
AB  - The X-ray structure analysis of a cross-linked crystal of concanavalin A soaked
      with the tripeptide molecule as the probe molecule showed electron density
      corresponding to full occupation in the binding pocket. The site lies on the
      surface of concanavalin A and is surrounded by three symmetry-related molecules.
      The crystal structure of the tripeptide complex was refined at 2.4-A resolution
      to an R-factor of 17.5%, (Rfree factor of 23.7%), with an RMS deviation in bond
      distances of 0.01 A. The model includes all 237 residue of concanavalin A, 1
      manganese ion, 1 calcium ion, 161 water molecules, 1 glutaraldehyde molecule, and
      1 tripeptide molecule. This X-ray structure analysis also provides an approach to
      mapping the binding surface of crystalline protein with a probe molecule that is
      dissolved in a mixture of organic solvent with water or in neat organic solvent
      but is hardly dissolved in aqueous solution.

PMID- 11330350
TI  - Reactivation kinetics of guanidine hydrochloride-denatured creatine kinase
      measured using the substrate reaction.
AB  - Guanidine hydrochloride-denatured creatine kinase (CK) can very quickly form a
      dimer with reactivity when the denaturant is diluted into the reaction system in
      the presence of DTT or EDTA. Tsou's method and its applied equation [Tsou (1988),
      Adv. Enzymol. Rel. Areas Mol. Biol. 61, 381-436; Yang and Zhou (1998), Biochim.
      Biophys. Acta 1388, 190-198] were used to measure the kinetic reactivation rate
      constants and the reactivation degree for reassociated CK dimers. Partial
      reactivation (about 50% at best) occurred following a monophasic course during
      the substrate reaction when compared with previous time interval measurements.
      The reactivation degree increased with increasing DTT (0.1-5 mM) and EDTA (0.1-1
      mM) concentrations. The apparent forward rate constants do not change with
      concentration, showing that the reactivation is a reversible first-order
      reaction, but not of complex formation type. However, the apparent forward rate
      constants do change with EDTA concentration, showing that the reactivation with
      EDTA is a reversible first-order reaction as well as of complex formation type.
      Excess DTT concentrations have an inhibitory effect, indicating that the
      excessive EDTA acts as a metal chealate not only for free Mg2+, but also for
      MgATP during the enzyme catalysis. This study shows that additional information
      about the reactivation of CK can be obtained from examining the substrate
      reaction. The possible refolding pathway of CK is discussed.

PMID- 11330351
TI  - Peptide phage display library as source for inhibitors of clostridial
      neurotoxins.
AB  - Clostridial neurotoxins are the most powerful toxins known. There are no
      available antidotes to neutralize neurotoxins after they have been internalized
      by neuronal cells. Enzymatic domains of clostridial neurotoxins are zinc
      endopeptidases specific for protein components of the neuroexocytosis apparatus.
      Thus, attempts were made to find such antidotes among molecules possessing
      chelating properties. Subsequently, it was proposed that the process of
      interaction between clostridial neurotoxins and their substrates might be more
      complex than viewed previously and may include several separate regions of
      interaction. Phage display technology is free from bias toward any particular
      model. This technology in combination with recombinantly produced light chains of
      botulinum neurotoxins serotypes A, B, and C was used to identify potential
      inhibitors of clostridial neurotoxins. Identified sequences did not show
      substantial similarity with substrate proteins of clostridial neurotoxins.
      Nevertheless, three peptides chosen for further analysis were able to inhibit
      enzymatic activity of all clostridial neurotoxins tested. This work demonstrates
      that at least one of these peptides could not be cleaved by clostridial
      neurotoxin. Attempts to delete amino acid residues from this peptide resulted in
      dramatic loss of its inhibitory activity. Finally, this work presents a novel
      approach to searching for inhibitors of clostridial neurotoxins.

PMID- 11330352
TI  - The participation of human serum albumin domains in chemical and thermal
      unfolding.
AB  - Fluorescence spectroscopy and differential scanning calorimetry were used to
      follow local and global changes in human serum albumin domains during chemical
      and thermal denaturation of this protein. Results suggests that thermal and
      chemical treatments involved an unfolding pathway of at least two steps and that
      domain IIA is not homogeneous. Unfolding at site I exposes a larger hydrophobic
      area to the solvent than at site II. The bilirubin-binding site showed atypical
      behavior: a significant increase in the hydrophobic area was exposed to the
      solvent when its binding site was denatured by guanidine hydrochloride. This
      result might be due to the high specificity of the bilirubin-binding site, whose
      binding makes an extensive conformational change in the environment of this site.

PMID- 11330353
TI  - Multidomain structure of a recombinant streptokinase. A differential scanning
      calorimetry study.
AB  - The temperature dependence of the heat capacity function of a recombinant
      streptokinase (rSK) has been studied by high-sensitivity differential scanning
      microcalorimetry and circular dichroism as a function of pH in low- and high
      ionic strength buffers. At low ionic strength it is found that this protein,
      between pH 7 and 10, undergoes four reversible and independent two-state
      transitions during its unfolding, suggesting the existence of four domains in the
      native structure of the protein. This result reconciles previous conflicting
      reports about the number of domains of this protein obtained by differential
      scanning calorimetry and small-angle X-ray scattering. The number of two-state
      transitions decreases when the pH of the medium is decreased, without noticeable
      changes in its circular dichroism spectrum. A plausible localization of the four
      domains in the streptokinase sequences is proposed and their thermodynamic
      parameters are given. Increase of ionic strength to 200 mM NaCl affects
      positively the protein stability and confirms the existence of four reversible
      two-state transitions. Above 200 mM NaCl the protein stability decreases,
      resulting in low percentage of reversibility, and even irreversible transitions.

PMID- 11330354
TI  - Protein-binding polynomials.
AB  - Using a new method recently published for analyzing the binding isotherms of
      biopolymers (Poland, 2000a), we calculate the complete binding polynomials for
      lysozyme, insulin, and serum albumin from published titration data. These three
      proteins have, respectively, 22, 32, and 184 dissociable protons and hence are
      represented by series in powers of the hydrogen ion concentration with the
      highest powers in the series being the numbers just indicated. Given the complete
      binding polynomial, the distribution function giving the concentration of all
      states of proton binding can then be calculated at any pH.

PMID- 11330355
TI  - Immunopharmacology of antibiotics: direct and indirect immunomodulation of
      defence mechanisms.
AB  - Antibiotics can alter the host's reaction to an infection (itself an
      immunomodulating event) in various ways. Indirect actions involve killing of
      bacteria, changing the intestinal flora, intrinsic antigenicity and preventing
      bacteria making virulence factors. Direct actions are upon phagocytic function,
      chemotaxis and lymphocyte activities. Immunomodulation can be positive ("pro
      host") or negative, and can be quantitated by means of the parameter "immune
      index". Among the cephalosporins, cefodizime shows the greatest positive
      immunomodulating activity, due to the unique nature of the 3-sidechain.
      Cefotaxime has an immunodepressing effect in vitro. The oral cephalosporin
      cefaclor appears to have a beneficial effect on polymorph function. While
      immunomodulation by antibiotics may appear marked in in vitro and ex vivo
      experiments, and in animal models, this phenomenon does not appear to have
      decisive effects therapeutically.

PMID- 11330356
TI  - Cefixime in urinary tract infections with special reference to pediatrics:
      overview.
AB  - Cefixime is a third-generation oral cephalosporin that is highly active against a
      broad range of gram-negative and some gram-positive aerobic bacteria. In non
      complicated urinary tract infections it is at least as effective as other usual
      treatments, and has a low rate of side effects. Several clinical studies have
      been performed on cefixime in urinary tract infections both in adults and
      children. On the basis of the literature data, cefixime could be indicated in the
      treatment of non-complicated urinary tract infections in children either as
      monotherapy or as switch therapy.

PMID- 11330357
TI  - Prediction of in-vivo efficacy by in-vitro early bactericidal activity with oral
      beta-lactams, in a dose-ranging immunocompetent mouse sepsis model, using strains
      of Streptococcus pneumoniae with decreasing susceptibilities to penicillin.
AB  - Killing curves and a sepsis model were performed with Streptococcus pneumoniae
      strains (MICs of penicillin = 0.01, 1, 2 and 4 mg/L) to assess the in vivo effect
      of in vitro early bactericidal activity. Optimal bactericidal concentration (OBC)
      was defined as the minimal concentration needed to obtain the maximal
      bactericidal activity during the sampling time for colony counting in killing
      curves. Animals were treated with amoxycillin, cefuroxime or cefpodoxime every 8
      h for 48 h, with doses ranging from 2.5 to 50 mg/kg. ED100 (minimal antibiotic
      dose obtaining a 100% survival) was used as efficacy endpoint. Cmax/MIC, AUC/MIC
      and deltaT >MIC did not accurately predict efficacy against the most resistant
      strains, deltaT >OBC being the most predictive efficacy parameter indicating the
      in vivo effect of early bactericidal activity. Lower deltaT >OBC values for
      amoxycilin vs oral cehalosporins were needed for efficacy. The higher early
      bactericidal activity of amoxycillin may explain its higher in vivo efficacy.

PMID- 11330358
TI  - Studies on the development and stability of resistance of Helicobacter pylori to
      metronidazole and clarithromycin.
AB  - Thirty-one strains of Helicobacter pylori, susceptible to metronidazole and
      clarithromycin, were isolated from 31 biopsy samples from patients with various
      gastric pathologies. We investigated the possibility of selecting resistant
      strains and the stability of resistance by exposing isolates to increasing
      subinhibitory concentrations of metronidazole and clarithromycin using a serial
      passages technique. Resistance to metronidazole was obtained in 100% of the
      isolates, while 32.2% displayed resistance to clarithromycin. Resistance to
      metronidazole was stable in 93.5% (29 of 31) of the isolates, whereas 100% (10 of
      10) of the strains were stably resistant to clarithromycin. The stability of the
      resistance that occurred after three passages on medium containing the two drugs
      was statistically significant (P <0.001). Thus, the technique of serial passages
      in vitro could be useful as a first screening in selecting drugs for use in
      therapeutic protocols for clinical trials.

PMID- 11330359
TI  - Antibiotic use and development of resistance in blood culture isolates: 8 years
      of experience from a cancer referral center.
AB  - The consumption of antimicrobial agents in a Slovakian national cancer institute
      from 1989-1996 was compared with resistance rates in clinically significant blood
      culture isolates. We observed an increase in resistance of viridans streptococci
      to penicillin and of enterococci to ampicillin. Resistance to vancomycin and
      teicoplanin was stable over the entire period despite a 20-fold increase in
      vancomycin consumption. Nor did we observe increased resistance to ofloxacin
      despite a 10-fold increase in consumption. Consumption of aminoglycosides and
      resistance levels were both stable. A different situation was observed with third
      generation cephalosporins, where resistance of Pseudomonas aeruginosa,
      Stenotrophomonas maltophilia and Acinetobacter spp. to ceftazidime and cefotaxime
      increased with increasing consumption. Resistance of Enterobacteriaceae to
      cefotaxime and ceftazidime was stable. Resistance to imipenem did not change
      significantly. However, the number of Stenotrophomonas maltophilia bacteremias
      increased significantly after imipenem was introduced in 1991. Because of
      improved outcome in bacteremia, an increased incidence of both gram-negative and
      gram-positive bacteremia led to only a slight increase in associated mortality.

PMID- 11330360
TI  - Transferable antibiotic resistance in multiresistant nosocomial Acinetobacter
      baumannii strains from seven clinics in the Slovak and Czech Republics.
AB  - Sixty-seven multiresistant nosocomial Acinetobacter baumannii isolates from
      patients hospitalized mostly in intensive care units of seven clinics in Slovak
      and Czech Republic were tested to determine their ability to transfer antibiotic
      resistance. All isolates were resistant to kanamycin, ticarcillin, cephalothin,
      cefotaxime, ceftazidime, aztreonam and susceptible to carbapenems, sulbactam and
      ampicillin/sulbactam. Sixty-five out of 67 strains transferred resistance
      determinants to Escherichia coli K-12 and Proteus mirabilis P-38 recipients.
      Analysis of selected transconjugants by an indirect selection method showed a
      more variable pattern of transferred resistance determinants. The clonal spread
      of strains transferring resistance seems to be an additional risk for occurrence
      of strains resistant to ceftazidime and aztreonam.

PMID- 11330361
TI  - Antimicrobial resistance of Streptococcus pneumoniae at a university hospital in
      Saudi Arabia.
AB  - The resistance pattern of 105 consecutive strains of Streptococcus pneumoniae
      isolated from patients at King Abdulaziz University Hospital (KAUH), Jeddah,
      Saudi Arabia over a 2-year period (March 1998 to February 2000) was determined
      with the minimal inhibitory concentration (MIC) method using E-test. Overall 6.7%
      of the isolates were penicillin resistant (MICs > or = 2 mg/L), and 51% were
      intermediate (MICs 0.12-1 mg/L). The resistance rates to ampicillin, cefotaxime,
      ceftriaxone, imipenem, erythromycin and clarithromycin were 8.6%, 8.6%, 4.7%,
      3.8%, 13%, and 21% respectively. High-level resistance was noted against
      cotrimoxazole and chloramphenicol, 76% and 68% respectively. Only 2.8% of S.
      pneumoniae were resistant to amoxycillin-clavulanate; no resistance to vancomycin
      was observed. Against penicillin-intermediate pneumococcal strains, vancomycin,
      ceftriaxone, cefotaxime and amoxycillin-clavulanate were the most active
      compounds. Against penicillin-resistant pneumococci, vancomycin was the most
      powerful agent, amoxycillin-clavulanate was half as active, whereas ceftriaxone,
      cefotaxime and imipenem were 4-fold less active than vancomycin. Fifty-six (53%)
      of the 105 pneumococcal strains were multi-drug resistant.

PMID- 11330362
TI  - Prevalence of penicillin-resistant Streptococcus pneumoniae in Kuwait.
AB  - The worldwide incidence of penicillin-resistant Streptococcus pneumoniae has
      increased at an alarming rate during the past decade. However, there has been
      little published data about the extent of this problem in Kuwait. The present
      study was undertaken to ascertain the preponderance of S. pneumoniae, either
      resistant or intermediate-resistant to penicillin, other beta-lactams and non
      beta-lactam antimicrobials in Kuwait. Two hundred and fifty fresh isolates from
      as many patients suffering from different clinical conditions were collected from
      all clinics and hospitals in Kuwait. Optochin sensitivity and bile solubility
      tests reconfirmed these. Susceptibility testing to penicillin, ampicillin,
      cefuroxime, ceftriaxone, cefotaxime, imipenem, erythromycin, chloramphenicol,
      ciprofloxacin and vancomycin was done using E-test strips and to oxacillin,
      tetracycline, trimethoprim and amoxicillin-clavulanate by disc diffusion
      technique. Full and intermediate resistance to penicillin was observed in 1.6%
      and 52.8% of the isolates respectively. Full resistance to third-generation
      cephalosporins ranged from 0.4% to 3.2%, however, intermediate resistance to
      these antibiotics varied between 18.8% and 21.2%. Ampicillin resistance was noted
      in 0.8%, but 40.4% of isolates were intermediately resistant. However, only 0.4%
      of the isolates showed either intermediate or full resistance to amoxicillin
      clavulanate. Resistance to imipenem was observed in 0.4% and intermediate to
      13.6% of the organisms. The rates of S. pneumoniae resistant to chloramphenicol,
      erythromycin, tetracycline and trimethoprim were between 8.4% and 37.6% and
      intermediate resistance between 1.2% and 17.6% while only 0.4% showed resistance
      to ciprofloxacin and none to vancomycin. Multiresistance to both beta-lactam and
      non-beta-lactam antibiotics was observed in 52% of the penicillin-resistant
      isolates.

PMID- 11330363
TI  - Disk diffusion method for fluconazole susceptibility testing of Candida albicans
      strains.
AB  - This study evaluated the usefulness of the disk diffusion method by using
      different media for the susceptibility testing of fluconazole against Candida
      albicans strains. The susceptibility of 108 clinical isolates of C. albicans
      against fluconazole were determined by microdilution and disk diffusion methods
      by using RPMI 1640 agar and 25 microg disks. 93 of these isolates were also
      tested by disk diffusion technique on four different media (yeast nitrogen base
      agar, Sabouraud dextrose agar, Mueller Hinton agar and Mueller Hinton methylene
      blue agar). The results of the microdilution method were evaluated visually and
      optically. The disk diffusion results were determined after 24 and 48 hours of
      incubation. When the 24-hour zone diameters were compared to the minimal
      inhibitory concentrations determined visually and optically, the best results
      were obtained for RPMI 1640 agar and yeast nitrogen base agar. The correlation
      coefficients were r=-0.34, -0.41 and r=-0.33, -0.32 for the first and second
      media, respectively. The best values (r=-0.29, -0.39) were obtained for Mueller
      Hinton methylene blue agar when the 48-hour zone diameters were considered.
      Agreement between the disk diffusion and microdilution methods was best for RPMI
      1640, yeast nitrogen base and Mueller Hinton methylene blue agar after 24 hours
      of incubation (87-89%, 88-90%, 93-96%, respectively) and for Mueller Hinton
      methylene blue agar after 48 hours of incubation (89-96%). Disk diffusion method
      using RPMI 1640, yeast nitrogen base and Mueller Hinton methylene blue agar
      appears to be a useful, rapid and reliable screening technique for testing the
      susceptibility of C. albicans strains to fluconazole.

PMID- 11330364
TI  - Effects of continuous or pulsed exposure to rifabutin and sparfloxacin on the
      intracellular growth of Staphylococcus aureus and Mycobacterium tuberculosis.
AB  - The time-kinetics of the intracellular bioactivity and intracellular post
      antibiotic effect (PAE) of rifabutin and sparfloxacin against Staphylococcus
      aureus and Mycobacterium tuberculosis, grown in human monocytes, were evaluated.
      Intracellular bactericidal activity against staphylococci was shown in the
      presence of extracellular drug concentrations equal or superior to 1/10 plasma
      Cmax. The bactericidal activity of rifabutin was dependent on both its
      extracellular concentrations and the exposure time. In contrast, the pattern of
      the intracellular activity of sparfloxacin was characterized by a minimal
      concentration dependent killing. Both antibiotics (from 1/10 to the expected lung
      Cmax) showed intracellular bioactivity against M. tuberculosis H37Ra and H37Rv
      strains. A long intracellular PAE on staphylococci (>4 hours) was demonstrated
      when drugs were removed from the infected monocytes after 1 h treatment. Our
      findings suggest that rifabutin and sparfloxacin may be useful in the treatment
      of lower respiratory tract infections due to intracellular pathogens.

PMID- 11330365
TI  - Duration of clinical symptoms in female patients with acute urethral syndrome
      caused by Chlamydia trachomatis treated with azithromycin or doxycycline.
AB  - One hundred fifty-one female patients with acute urethral syndrome caused by
      Chlamydia trachomatis were examined. First, patients were divided into two
      groups, those with clinical symptoms present < 3 weeks before the start of
      treatment, and those with clinical symptoms > or = 3 weeks prior to the beginning
      of therapy. Then patients were further divided into groups and randomized to
      receive azithromycin once daily in a single dose of 1.0 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 (8 study groups in all). Clinical and bacteriological efficacy was
      evaluated 3 weeks after the end of therapy. In the group of patients with disease
      symptoms lasting for 3 weeks or longer, the eradication and clinical cure rates
      were significantly higher after administration of azithromycin in a dose of 1x500
      mg/6 days than after a single dose of 1.0 g (p<0.01), and after administration of
      doxycycline 2x100 mg/14 days than by using doxycycline 2x100 mg/7 days (p<0.05).

PMID- 11330366
TI  - Postoperative infections following total knee replacement: an epidemiological
      study.
AB  - From January 1991 to June 1997 217 patients undergoing monolateral or bilateral
      total knee replacement (TKR) were consecutively enrolled in a prospective study
      on the incidence of postoperative infections and related risk factors. Regional
      antimicrobial prophylaxis (teicoplanin 400 mg) was used in 263 (95%) prostheses
      implanted; in the remaining 14 implants (5%) perioperative antibiotic prophylaxis
      (teicoplanin 800 mg) was administered as usual by systemic route. None of the
      patients experienced local or systemic adverse effects. Over the 2-year follow-up
      period, 8 (2.9%) primary site infectious complications were recorded, i.e. 4
      superficial infections, which were cured without involvement of the prostheses,
      and 4 deep infections, which required prosthesis removal. Six infections occurred
      in patients who had undergone previous surgery of the same knee joint, and 2 in
      patients undergoing primary TKR (p= 0.0005); diabetic patients had infections
      (13%) more frequently than non-diabetic patients (1.9%, p=0.01). Staphylococci
      were the leading organisms isolated from infections; however 3 strains of
      Escherichia coli were isolated from patients who had undergone a previous
      prosthesis implantation at the same knee joint. Regional administration of
      teicoplanin appears to be a safe and valuable prophylactic technique; however, in
      patients at risk of infection a prophylactic regimen which is also active against
      gram-negative bacteria should probably be considered.

PMID- 11330367
TI  - Dynamics of viral load in plasma and HIV DNA in lymphocytes during highly active
      antiretroviral therapy (HAART): high viral burden in macrophages after 1 year of
      treatment.
AB  - In this study we evaluated the level of HIV RNA in plasma and HIV DNA in
      peripheral blood cells. Sixteen antiretroviral-experienced HIV patients with
      severe immune suppression were included in the study. After the first month,
      56.2% of the patients showed undetectable levels of HIV RNA, this percentage
      remaining stable after 1 year (53.3%). At enrollment, 7 patients (43.7%) with a
      low CD4+ T cell count (mean 22 per mm3 versus 73) showed HIV DNA levels below the
      limit of detection (5 copies/10(5)) in lymphocytes. They all subsequently had
      increased HIV DNA that became detectable between the first and the third month of
      therapy, associated with an increase of the CD4+ T cell count (mean 22 to
      95/mm3); in 4 of these patients this increase was transitory, becoming
      undetectable again after one year. In 7 out of the 8 patients with detectable HIV
      DNA at enrollment, the HIV DNA level decreased over time. Seven out of 15
      patients at 1 year (46.7%) showed both undetectable levels of HIV RNA in plasma
      and HIV DNA in lymphocytes (p<0.05); these patients had a higher CD4+ T cell
      count at baseline (mean 75 versus 25/mm3) and a higher increase (306 versus
      177/mm3) after 1 year. PCR-based dilution assay carried out at 1 year showed that
      all patients had a consistent amount of HIV DNA positive- CD4+ T lymphocytes and
      macrophages, with higher values in these last cells. The data indicate that a
      durable reservoir of virus is still present in both lymphocytes and monocytes,
      even after long-lasting HAART treatment.

PMID- 11330368
TI  - Enterobacter spp. infections complicating the course of HIV disease.
AB  - Through a retrospective review of clinical and laboratory data of 2517
      consecutive patients with HIV disease hospitalized since 1991, 13 patients were
      identified (0.52%), who suffered from a confirmed Enterobacter spp. infection
      (urinary tract disease in 7 cases, sepsis in 4 patients, and pneumonia in 2
      cases). A severe immunodeficiency was recognized in all cases, as expressed by a
      mean CD4+ lymphocyte count <60 cells/microL, and frequently, a prior diagnosis of
      AIDS. Bloodstream infection proved linked to a lower mean CD4+ cell count, a more
      frequent occurrence of leukopenia-neutropenia, and nosocomial origin of the
      infecting pathogen. Hospital-acquired Enterobacter spp. disease was more frequent
      than community-acquired, and was significantly associated with leukopenia
      neutropenia, and a diagnosis of AIDS. Antibiotic susceptibility assays showed a
      resistance rate to ampicillin and cephalothin involving >90% of tested strains,
      and a higher (but varied) sensitivity to other beta-lactams, aminoglycosides,
      fluoroquinolones, and cotrimoxazole. Adequate chemotherapy provided clinical and
      bacteriological success in all evaluated patients, in the absence of mortality or
      relapses. Only 34 episodes of HIV-associated Enterobacter spp. infection have
      been reported to date in 11 different literature studies. Our data point out that
      also Enterobacter spp. organisms may have an appreciable pathogenic potential in
      patients with HIV disease, especially in those with a low CD4+ lymphocyte count,
      leukopenia-neutropenia, who are hospitalized. Despite the unpredictable
      antibiotic susceptibility profile of these organisms, HIV-related Enterobacter
      spp. disease may be properly managed through rapid identification and timely and
      appropriate antimicrobial treatment.

PMID- 11330369
TI  - A three-drug regimen (gemcitabine, ifosfamide and cisplatin) for advanced non
      small-cell lung cancer.
AB  - We have carried out a pilot study on 25 non-small cell lung cancer patients,
      administering the combination of gemcitabine at the dose of 1000 mg/m2 on days 1
      and 8, ifosfamide 1500 mg/m2 on days 1 and 2 (plus mesna as uroprotector) and
      cisplatin 40 mg/m2 on days 1 and 2, every 21 days. Granulocyte Colony Stimulating
      Factor was employed in all cases from day 10 to day 18 at the dose of 300 microg
      daily. An objective response was observed in 11 cases (44%). The regimen was
      active, but toxicity was remarkable with some cases of severe myelosuppression
      and mucositis.

PMID- 11330370
TI  - Dacarbazine-induced carotid artery and deep venous thrombosis in a patient with
      leiomyosarcoma: case report.
AB  - Thromboembolic events are a common and important cause of morbidity and mortality
      in cancer patients that require early diagnosis and treatment. Reports have
      suggested that chemotherapeutic agents may contribute to this risk. In this case
      report, a 60-year-old male patient on chemotherapy (dacarbazine and doxorubicin)
      for leiomyosarcoma with no previous history of thromboembolism developed left
      carotid artery thrombosis 3 days after the first cycle of chemotherapy. A low
      molecular weight heparin was started for a possible cerebrovascular accident
      related thrombosis. In the second cycle, he developed right femoral vein
      thrombosis only 2 days after initiating the chemotherapy. The chemotherapy
      protocol was changed and the patient did not develop any thrombosis during the 1
      year follow-up. In the literature, no thrombotic complications have previously
      been reported due to either dacarbazine or doxorubicin. In conclusion, elderly
      patients on chemotherapy should be carefully monitored for thromboembolic
      complications and, in case of thrombosis, the chemotherapy protocol should be
      changed.

PMID- 11330371
TI  - Postoperative neurosurgical site infection surveillance.

PMID- 11330372
TI  - Isolation frequency and antimicrobial susceptibility of Pseudomonas aeruginosa
      bloodstream infections in neutropenic patients with acute leukemia.

PMID- 11330373
TI  - Laparoscopic repair of ventral and incisional hernias using a new composite mesh
      (Parietex): initial experience.
AB  - Ventral hernia repair is still a difficult problem for surgeons because of the
      high recurrence rate and possible postoperative complications. Repairs with a
      prosthesis have reduced the recurrence rate, but the anterior approach still
      involves high morbidity and a long hospital stay. The purpose of this article was
      to evaluate the results of laparoscopic surgery on ventral hernias using a new
      double-layer mesh in an intra-abdominal position. A retrospective analysis was
      performed of the first 20 patients undergoing laparoscopic surgery for ventral
      hernia (75% incisional and 25% umbilical) with intra-abdominal prosthetic repair
      using a double-layer mesh consisting of three-dimensional multifiber polyester on
      one side and a hydrophilic resorbable nonstick collagen membrane on the other
      (Parietex composite, Sofradim, Villefranche sur Saone, France). The procedure was
      done on an outpatient basis in 85% of the cases. There was no morbidity or
      mortality. During a mean follow-up period of 10 months we found no infections,
      rejections, fistulas, recurrences, or alterations in bowel function. Laparoscopic
      repair of ventral hernias is an efficient alternative to open repair, with a low
      morbidity rate and short hospital stay. The double-layer mesh is safe for intra
      abdominal use.

PMID- 11330374
TI  - Experimental use of an illuminated and magnetic tip, flow-directed pulmonary
      artery catheter for lung resection.
AB  - The authors performed a study to design and evaluate a device giving the surgeon
      added protection against pulmonary artery injury in a closed thoracic
      compartment. Eleven swine were used for a total of 12 lobectomies. A light
      bearing, magnetic-tipped, modified Swan-Ganz catheter was passed through the
      jugular vein into the left pulmonary artery. By using magnetic guidance through a
      port site and balloon inflation, cessation of flow in the pulmonary artery was
      documented by Doppler. Twelve video-assisted lobectomies were performed. Nine of
      12 (75%) lobectomies were completed successfully by using the magnetic-tipped,
      illuminated balloon catheter. In 4 cases, the catheter displaced because of the
      short left main pulmonary artery in swine. In one case, the balloon was
      recovered, and successful lobectomy was performed. The use of a magnetic-tipped,
      flow-directed device may provide an effective means of endovascular control
      during thoracoscopic pulmonary arterial dissection.

PMID- 11330375
TI  - Laparoscopic approach for esophageal achalasia with epiphrenic diverticulum.
AB  - We report the case of a 65-year-old woman with a 10-year history of dysphagia,
      regurgitation, cough, and 10-kg weight loss caused by an epiphrenic diverticulum
      associated with esophageal achalasia managed with a laparoscopic approach. A
      preoperative barium swallow showed a dilated sigmoid esophagus with a 6-cm
      epiphrenic diverticulum. Esophageal manometry confirmed the absence of
      peristalsis in the esophageal body. We performed a laparoscopic diverticulectomy
      and a 7-cm distal esophageal myotomy with a Dor fundoplication. The postoperative
      course was uneventful. On the third postoperative day a barium swallow showed no
      leak, and the patient started oral intake. She was discharged home 5 days after
      the operation free of symptoms and tolerating a soft diet. Sixteen months after
      surgery, she was asymptomatic and had gained 8 kg. A barium swallow showed a
      normal-size esophagus with regular emptying. We reaffirm the feasibility, safety,
      and efficacy of the laparoscopic diverticulectomy and distal myotomy with Dor
      fundoplication to manage epiphrenic diverticula resulting from esophageal
      achalasia.

PMID- 11330376
TI  - Laparoscopic resection of an extraesophageal leiomyoma presenting as an intra
      abdominal mass.
AB  - Leiomyomas comprise fewer than 1% of esophageal neoplasms. Only 2% of leiomyomas
      are extraesophageal, and the remainder are intramural or intraluminal. A presumed
      intra-abdominal mass found at diagnostic laparoscopy was discovered to be an
      extraesophageal leiomyoma. Esophageal leiomyoma enucleation is most commonly
      accomplished via a thoracotomy. Increasingly, thoracoscopy has been used. An open
      transhiatal approach has also been described. Our patient underwent an
      uncomplicated transhiatal laparoscopic esophageal leiomyoma resection and
      benefited from the commonly recognized advantages associated with minimally
      invasive surgery.

PMID- 11330377
TI  - Esophagectomy and laparoscopic gastric mobilization with minilaparotomy for
      tubulization and esophageal replacement.
AB  - Several alternatives for esophageal resection and replacement with laparoscopic,
      thoracoscopic, video-assisted, or completely endoscopic techniques have been
      reported. All of these have advantages and disadvantages according to the
      indications, instrumental requirements, cost, and feasibility. Here we report a
      new alternative procedure, performing the gastric mobilization and transhiatal
      esophageal dissection by laparoscopic approach and preparation of the gastric
      tube through a midline 5-cm minilaparotomy. In this manner we handled the GIA
      staplers outside of the abdomen, avoiding prolongation of the operating time and
      the excessive increase of the cost of the procedure. Further, this procedure may
      help to prevent the risk of postoperative leak of the stapler suture line by
      reinforcing this suture with a invaginating continuous manual 3-0 reabsorbable
      suture (Monocryl, Johnson & Johnson, Cincinnati, OH, U.S.A.). A left
      anterolateral cervicotomy was done to complete the dissection of the esophagus,
      and the gastric tube was ascended through a retrosternal tunnel to the neck for
      esophagogastroanastomosis. We operated on a 73-year-old woman, who had a T1
      squamous carcinoma of middle third of the esophagus. The operation was performed
      with no intraoperative complications as a result of the procedure. After surgery,
      pneumonia with a pleural effusion developed and was evacuated. The patient was
      discharged from the hospital with no symptoms. We believe that this is a safe,
      inexpensive, and easy procedure for the transhiatal laparoscopic esophagectomy
      and its replacement by a gastric tube.

PMID- 11330378
TI  - Laparoscopic double cholecystectomy.
AB  - Gallbladder anomalies, although rarely seen, can be a challenge to the surgeon.
      There are many cases in the literature in which double gallbladder has been
      missed at the first operation. A case in which accessory gallbladder was
      suspected, confirmed at the operation, and managed successfully by laparoscopic
      cholecystectomy is described. The lack of specific symptoms and findings and the
      inaccuracy of imaging methods may cause missed diagnoses. The laparoscopic
      surgeon should always be aware of this abnormality.

PMID- 11330379
TI  - Extraction of retained gallstones from an abscess cavity: a percutaneous
      endoscopic technique.
AB  - A novel technique to retrieve spilled gallstones in an abscess cavity with the
      use of minimally invasive techniques is described.

PMID- 11330380
TI  - Percutaneous management of multiple bilateral liver abscesses complicating Crohn
      disease.
AB  - Liver abscess is a rare complication of Crohn disease. A case of multiple,
      bilateral, pyogenic liver abscesses appearing as a recurrent manifestation of
      Crohn disease in a 34-year-old man is reported. Conservative management with
      antibiotics, double-catheter drainage, and multiple aspirations was successful.
      The liver abscesses disappeared with no recurrence during a 5-year follow-up
      period.

PMID- 11330381
TI  - Videolaparoscopic management of percutaneous liver biopsy complications.
AB  - Percutaneous liver biopsy is a routine procedure in the diagnosis, management,
      and follow-up of several liver disorders. Mortality and morbidity rates from
      percutaneous liver biopsy are low. This report of three cases of serious
      percutaneous liver biopsy complication and their management highlights the role
      played by videolaparoscopy as a diagnostic and therapeutic procedure in two
      different types of PLB complication: hemobilia and bile peritonitis. In two
      patients, intrahepatic arteriobiliary fistula developed with gastrointestinal
      hemorrhage (hemobilia). Both were treated with cholecystectomy and ligation of
      the right branch of the hepatic artery. In the third case, the percutaneous liver
      biopsy needle punctured the gallbladder, leading to bile peritonitis and acute
      abdomen, and the patient underwent videolaparoscopic cholecystectomy with
      aspiration and lavage of the abdominal cavity. Videolaparoscopic procedures are
      an adequate alternative for the management of serious percutaneous liver biopsy
      complications such as hemobilia and bile peritonitis. The advantages of a
      videolaparoscopy include low morbidity rates, quick recovery, good cosmetic
      result, and ability to resolve the complications of percutaneous liver biopsy.

PMID- 11330382
TI  - Hand-assisted laparoscopic distal pancreatectomy with minilaparotomy for distal
      pancreatic cystadenoma.
AB  - Two patients with cystic tumors of the pancreas treated by laparoscopic distal
      pancreatectomy are presented. The first patient was a 34-year-old woman with a 6
      cm cystadenoma of the tail of the pancreas treated with a complete laparoscopic
      distal pancreatectomy. After mobilization of the distal pancreas and spleen, the
      pancreas was transected proximally together with the splenic artery and vein
      using an endoscopic linear stapler. The second patient was a 71-year-old woman
      with a 6-cm cystadenoma of the body of the pancreas, treated by hand-assisted
      laparoscopic distal pancreatectomy with minilaparotomy because the tumor was
      adjacent to the portal vein and celiac axis. Using an upper median
      minilaparotomy, dissection of the gastrocolic ligament, division of the splenic
      artery, and transection and closure of the pancreas were performed. Division of
      the splenic vein and mobilization of the distal pancreas and spleen were
      performed via a hand-assisted laparoscopic approach. There were no postoperative
      complications (such as pancreatic fistulas) in either patient, and the
      postoperative courses were uneventful. The patients returned to normal activity
      within 1 week after the operation. Complete laparoscopic and hand-assisted
      laparoscopic distal pancreatectomy are preferable to conventional open surgery
      for benign tumors of the pancreas because of their less-invasive nature.
      Additionally, in tumors of the body of the pancreas, hand-assisted laparoscopic
      distal pancreatectomy might have the advantages of laparotomy and laparoscopy in
      terms of handling the splenic artery and vein just below the minilaparotomy site,
      suggesting an easier and safer procedure than complete laparoscopic distal
      pancreatectomy. Therefore, hand-assisted laparoscopic distal pancreatectomy can
      be recommended as a useful alternative to complete laparoscopic distal
      pancreatectomy for selected patients with benign tumors of the body and tail of
      the pancreas.

PMID- 11330383
TI  - Laparoscopic excision of retroperitoneal tumors: technique and review of the
      laparoscopic experience.
AB  - A technique for laparoscopic excision of benign retroperitoneal tumors, including
      a teratoma and two cystic lesions, is described. Laparoscopic resection of a 12
      cm retroperitoneal teratoma was accomplished with the patient in the left lateral
      decubitus position. Medial mobilization of the ascending colon and the duodenum
      was required for access to the lesion. Resections of two cystic lesions
      (measuring 20 cm and 12 cm) were performed with the patients in the lithotomy
      position. The colon required medial mobilization in both cases to gain access to
      the cysts. Once the cysts were dissected from surrounding structures, they were
      punctured, and the aspirated fluid was sent for cytologic analysis. There were no
      complications or conversions. Mean operating time was 122 minutes (range, 80
      190). Patients were discharged 1 day after surgery, requiring only nonsteroidal
      anti-inflammatory medications for analgesia. Retroperitoneal tumors can be
      resected laparoscopically with careful preoperative investigation and meticulous
      laparoscopic technique. A major advantage of laparoscopic resections is that the
      patient recovers rapidly with minimal morbidity.

PMID- 11330384
TI  - Treatment of inguinodynia after laparoscopic herniorrhaphy: a combined
      laparoscopic and fluoroscopic approach to the removal of helical tackers.
AB  - Laparoscopic inguinal herniorrhaphy has become a popular operation for the
      treatment of inguinal hernia. However, injury and entrapment of the cutaneous
      nerves of the lumbar plexus by the staples or tackers used for mesh fixation have
      been described. Laparoscopic removal of the staples or tackers in the inguinal
      region has been attempted with variable success. The success of the laparoscopic
      approach for removal of helical tackers in particular is sometimes limited by the
      fact that the offending tackers are deeply embedded in the preperitoneal tissues
      and not readily located with a simple laparoscopic view. The authors report a
      case in which fluoroscopy was used to help identify tackers that could not be
      visualized laparoscopically. The neuralgia disappeared after successful removal
      of the offending tackers with no neurologic deficit. Liberal use of fluoroscopic
      guidance in the laparoscopic removal of helical tackers in similar cases is
      recommended.

PMID- 11330385
TI  - Thoracoscopic sympathectomy.

PMID- 11330386
TI  - Thoracoscopic sympathectomy.

PMID- 11330387
TI  - Achalasia: the case for primary laparoscopic treatment.
AB  - Laparoscopic Heller myotomy offers the best-known surgical therapy for esophageal
      achalasia. Nevertheless, this procedure continues to compete with alternative
      endoscopic treatment and is often considered only as a secondary resort. In this
      study, the authors performed a review of the results of laparoscopic Heller
      myotomy and an evaluation of the impact of previous endoscopic treatment
      regarding perioperative complications and late results. Twenty-seven patients
      with achalasia confirmed by a manometry examination underwent a primary
      laparoscopic Heller myotomy (group 1, n = 14) or experienced endoscopic treatment
      failure (group 2, n = 13). A dysphagia score (0-4) was obtained before and after
      surgery. Clinical course was reviewed at 2 months and then every 6 months after
      surgery. In December 1999, patients answered a questionnaire regarding surgery
      satisfaction, postoperative reflux, and dysphagia for statistical analysis. There
      were no deaths. Mean hospital stay was 5.6 days. Three perforations occurred in
      group 2 (25%) versus one in group 1 (6%) (not statistically significant). At a
      mean 27-month follow-up, the dysphagia score was significantly (P < 0.001)
      improved in both groups but more significantly in group 1 versus group 2 (not
      statistically significant). Only one patient in group 2 reported heartburn. All
      patients in group 1 (100%) were satisfied with surgery as opposed to 10 of 13
      patients (75%) in group 2 (P < 0.10). Primary laparoscopic Heller myotomy appears
      to be the treatment of choice for achalasia. Previous endoscopic treatment
      increases intraoperative complications and may affect long-term results.

PMID- 11330388
TI  - Laparoscopic gastrostomy: results of 121 patients over 7 years.
AB  - Laparoscopic gastrostomy was introduced in various technical variants 7 years
      ago. However, larger series and long-term results of these new methods are still
      lacking. In a prospective study, laparoscopic gastrostomies were performed by two
      institutions in 121 patients (88 men, 33 women; mean age, 58.3 +/- 11.16 years
      [range, 24-82]) with esophageal stenosis in locally advanced hypopharyngeal or
      oropharyngeal carcinoma, incurable esophageal carcinoma, and cerebral dysphagia.
      Operating time was 40 +/- 22 (range, 10-160) minutes. Procedure-related mortality
      was 0%, early mortality was 1.6%, the overall intraoperative complication rate
      was 7.4%, and the early complication rate was 9.9%. During a cumulative usage
      time of 1086.2 months, the complication rate in 1000 usage days was 0.8, and the
      stoma infection rate was 0.65. Laparoscopic gastrostomy is a reliable method for
      safe and economic establishment of enteral nutrition, even in patients for whom
      long-term nutrition by gastrostomy is expected.

PMID- 11330389
TI  - Early experience with laparoscopic radical gastrectomy for advanced gastric
      cancer.
AB  - Use of the laparoscopic approach for the management of gastric cancer is still in
      the developmental phase. The authors present their experience with laparoscopic
      radical gastrectomy for advanced gastric cancer. Between September 1997 and
      August 1999, four laparoscopic gastrectomies for gastric carcinoma were performed
      on two male and two female patients (mean age, 61.5 years). One D2 total radical
      gastrectomy and three D2 subtotal distal gastrectomies were performed, using a
      totally laparoscopic approach. Mean operative time was 210 minutes. There were no
      intraoperative complications. All four patients recovered uneventfully from
      surgery and began oral feeding on the third postoperative day. Median
      postoperative stay was 7 days (range, 6-9). All patients were alive 8 months to 3
      years after the operation, with no cancer recurrences. This series shows that
      laparoscopic radical gastrectomy for moderately advanced cancers can produce good
      results in terms of safety and oncologic adequacy.

PMID- 11330390
TI  - Ultrasonography incorrectly diagnoses gallbladder polyps.
AB  - To determine the accuracy of ultrasound-diagnosed polypoid lesions of the
      gallbladder in their institution, the authors reviewed the records of 41 patients
      with polypoid lesions of the gallbladder who underwent cholecystectomy, and
      collected data concerning age, sex, symptoms, and histopathologic diagnosis.
      Histopathologic evaluation confirmed polyps in only two patients (4.9%)
      categorized as having polypoid lesions of the gallbladder. Most specimens from
      patients with ultrasonography reports suggesting small polyps manifested
      cholesterolosis (17 of 41) or cholelithiasis (15 of 41). No specimen harbored
      malignancy. Mean patient age was 47.4 years, and the most common symptoms were
      pain (85%), nausea (44%), vomiting (29%), and abnormal liver function test
      results (14%). The accuracy of sonography for diagnosing polypoid lesions of the
      gallbladder was poor. Many of the small polyps seen on sonography most likely
      represented a stone embedded in the gallbladder wall or other abnormality.
      Because of the likelihood of cholelithiasis, the authors recommend that patients
      with biliary symptoms and ultrasonography findings suggesting polypoid lesions of
      the gallbladder undergo cholecystectomy.

PMID- 11330391
TI  - Outpatient laparoscopic cholecystectomy in Hong Kong: patient acceptance.
AB  - The authors performed a prospective evaluation of 60 Hong Kong Chinese patients
      with symptomatic gallstones and gallbladder polyps undergoing outpatient
      laparoscopic cholecystectomy in a regional hospital in Hong Kong from March 1996
      to May 1998 to determine the feasibility, satisfaction, and acceptance of this
      procedure among Chinese patients. Patients with American Society of
      Anesthesiologists grade I and II gallstones or polyps were selected. Exclusion
      criteria included 1) history of upper abdominal operations, attacks of acute
      cholecystitis, cholangitis, or pancreatitis; 2) abnormal liver function; and 3)
      ultrasonographic evidence of contracted gallbladder, thickened gallbladder wall,
      dilated common bile duct, or common bile duct stones. Patients discharged at 5:00
      PM on the day of cholecystectomy were defined as having undergone outpatient
      procedure. Patients were asked about procedure acceptance, rated on a scale of 1
      to 10 (best), using a standardized questionnaire 4 weeks after operation. The
      study included 21 men and 39 women with mean age of 40.5 years (range, 27-59).
      There were no conversions to open procedures in the series. There were 6 (10%)
      unanticipated postoperative hospital admissions; all patients were discharged on
      the first postoperative day. Another patient was readmitted 3 days after
      operation because of a common bile duct stone. Overall patient acceptance of
      outpatient laparoscopic cholecystectomy was good, with a mean score of 8.6 of 10.
      Thirteen patients (22%) expressed dissatisfaction with being discharged earlier
      than they had expected, and 9 (15%) would have preferred inpatient care. Forty
      eight patients (80%) resumed full daily activities by the first postoperative
      day; the remaining 12 did so by the end of the first week. Among the 44 working
      patients, only 4 (9%) resumed full duty within the first postoperative week; 29
      (66%) did so by the second week and the remaining 11 (25%) returned to work after
      the third week. By selecting appropriate subjects, outpatient laparoscopic
      cholecystectomy is feasible and highly accepted among Hong Kong Chinese patients.
      Approximately one quarter of the patients preferred a longer postoperative stay
      or inpatient care.

PMID- 11330392
TI  - Enteroscopy as a tool for diagnosing gastrointestinal bleeding requiring blood
      transfusion.
AB  - Iron-deficiency anemia secondary to gastrointestinal blood loss is a common cause
      of hospitalization. In many cases, the bleeding site cannot be defined despite
      thorough routine examination of the gastrointestinal tract. The aim of this study
      was to evaluate push enteroscopy as a diagnostic tool in patients with severe
      anemia, secondary to recurrent gastrointestinal bleeding, that required
      management by transfusion. Thirty-five consecutive push enteroscopy
      investigations were performed in 1998 and 1999 on 25 patients (15 men, 10 women).
      Mean age was 57 +/- 16 years (range, 33-83). All patients had received blood
      transfusions because of pronounced anemia secondary to gastrointestinal bleeding.
      Before push enteroscopy, all patients had been investigated with
      esophagogastroduodenoscopy, colonoscopy, and small-bowel radiography using the
      double contrast technique; no bleeding site was found. In addition, 10 of 25
      patients had been investigated beforehand with 99mTc-labelled red blood cell
      scintigraphy, and 5 of 25 with scintigraphy for Meckel diverticulum. Two patients
      were also investigated with angiography before the push enteroscopy, and in six
      patients an additional total intraoperative enteroscopy was performed, preceded
      by a new colonoscopy, esophagogastroduodenoscopy, and push enteroscopy. A
      bleeding site was disclosed in 15 of 25 (60%) patients. In 7 of 25 patients (28%)
      the bleeding site was found in the stomach or esophagus. even though the patients
      had undergone one or two esophagogastroduodenoscopies earlier with normal
      findings. Total intraoperative enteroscopy identified a bleeding site in four of
      six (67%) patients studied. Two patients had bleeding hemangiomas that were
      resected surgically. Two patients had small intestinal adenomas, one with
      adenocarcinoma in situ. Push enteroscopy performed with an overtube inserted
      under fluoroscopic guidance is an important diagnostic tool in patients in whom
      conventional examinations do not disclose bleeding sites. Interestingly, 28% of
      patients had bleeding within reach of the gastroscope, indicating that a new
      upper endoscopy should be recommended before push enteroscopy is performed. When
      no positive findings are seen on push enteroscopy and the patient is affected by
      severe, recurrent iron-deficiency anemia, total intraoperative enteroscopy should
      be considered.

PMID- 11330394
TI  - Identification of Lens culinaris ssp. culinaris chromosomes by physical mapping
      of repetitive DNA sequences.
AB  - We describe the characterisation and the chromosomal localisation of two repeated
      DNA sequences, named pLc30 (466 bp long, 64% AT residues) and pLc7 (408 bp long,
      61% AT residues), isolated from lentil (Lens culinaris ssp. culinaris) genomic
      DNA. The pLc30 family is characterised by four internal repeats organised in a
      head-to-tail orientation, whereas the pLc7 contains many short direct subrepeats.
      The two families do not share significant sequence similarity. The distribution
      of these repetitive sequences in different Lens species and in other legumes was
      investigated. pLc30 is present in all Lens species investigated but absent from
      other genera examined. In contrast, pLc7 is present also in the genome of other
      legumes. As determined by FISH, the pLc30 sequence hybridises on six out of seven
      lentil chromosome pairs, while pLc7 hybridises on one only. The distribution of
      the nine different hybridisation sites of pLc30 allows the discrimination of all
      seven chromosome pairs and the construction of a karyotype of L. culinaris ssp.
      culinaris. Additionally, the combination of simultaneous and successive FISH with
      pLc7, 5S rRNA, 18S-5.8S-25S rRNA genes, and a telomeric sequence allowed the
      assembly of a physical map based on lentil karyotype.

PMID- 11330395
TI  - Karyotyping mouse chromosomes by multiplex-FISH (M-FISH).
AB  - Karyotyping of mouse chromosomes is a skillful art, which is laborious work even
      for experienced cytogeneticists. With the growing number of mouse models for
      human diseases, there is an increasing demand for automated mouse karyotyping
      systems. Here, such a karyotyping system for mouse chromosomes based on the
      multiplex-fluorescence in-situ hybridization (M-FISH) technology is shown. The
      system was tested on a number of individual mice with numerical and structural
      aberrations and its reproducibility and robustness verified. Mouse M-FISH should
      be a valuable tool for the analysis of chromosomal rearrangements in mice.

PMID- 11330393
TI  - A model for chromosome structure during the mitotic and meiotic cell cycles.
AB  - The chromosome scaffold model in which loops of chromatin are attached to a
      central, coiled chromosome core (scaffold) is the current paradigm for chromosome
      structure. Here we present a modified version of the chromosome scaffold model to
      describe chromosome structure and behavior through the mitotic and meiotic cell
      cycles. We suggest that a salient feature of chromosome structure is established
      during DNA replication when sister loops of DNA extend in opposite directions
      from replication sites on nuclear matrix strands. This orientation is maintained
      into prophase when the nuclear matrix strand is converted into two closely
      associated sister chromatid cores with sister DNA loops extending in opposite
      directions. We propose that chromatid cores are contractile and show, using a
      physical model, that contraction of cores during late prophase can result in
      coiled chromatids. Coiling accounts for the majority of chromosome shortening
      that is needed to separate sister chromatids within the confines of a cell. In
      early prophase I of meiosis, the orientation of sister DNA loops in opposite
      directions from axial elements assures that DNA loops interact preferentially
      with homologous DNA loops rather than with sister DNA loops. In this context, we
      propose a bar code model for homologous presynaptic chromosome alignment that
      involves weak paranemic interactions of homologous DNA loops. Opposite
      orientation of sister loops also suppresses crossing over between sister
      chromatids in favor of crossing over between homologous non-sister chromatids.
      After crossing over is completed in pachytene and the synaptonemal complex breaks
      down in early diplotene (= diffuse stage), new contractile cores are laid down
      along each chromatid. These chromatid cores are comparable to the chromatid cores
      in mitotic prophase chromosomes. As an aside, we propose that leptotene through
      early diplotene represent the 'missing' G2 period of the premeiotic interphase.
      The new chromosome cores, along with sister chromatid cohesion, stabilize
      chiasmata. Contraction of cores in late diplotene causes chromosomes to coil in a
      configuration that encourages subsequent syntelic orientation of sister
      kinetochores and amphitelic orientation of homologous kinetochore pairs on the
      spindle at metaphase I.

PMID- 11330396
TI  - Loss of the Y chromosomal PAR2-region in four familial cases of satellited Y
      chromosomes (Yqs).
AB  - Applying fluorescence in-situ hybridization (FISH) of various Y chromosomal DNA
      probes to four familial cases of human Yqs, it was possible to demonstrate that
      the formation of Yqs must have arisen from a reciprocal translocation involving
      the short arm of an acrocentric autosome and the heterochromatin of the long arm
      of the Y chromosome (Yqh). Breakpoints map within Yqh and the proximal short arm
      of an acrocentric autosome resulting in the gain of a nucleolus organizer region
      (NOR) including the telomere repeat (TTAGGG)n combined with the loss of the
      pseudoautosomal region 2 (PAR2) at the long arm of the recipient Y chromosome. In
      no case could the reciprocal product of an acrocentric autosome with loss of the
      NOR and gain of PAR2 be detected. Using the 15p-specific classical satellite-III
      probe D15Z1 in two of the four Yqs probands presented here, it could be shown
      that the satellited material originated from the short arm of chromosome 15. In
      contrast to the loss of PAR2 in Yqs chromosomes, another Y chromosomal variant
      (Yqh-) showing deletion of long-arm heterochromatin in Yq12 has retained PAR2
      referring to an interstitial deletion of Yq heterochromatin in such deleted Y
      chromosomes.

PMID- 11330397
TI  - Identification and characterization of satellite III subfamilies to the
      acrocentric chromosomes.
AB  - The centromeres and the short arms of the five pairs of acrocentric chromosomes
      in humans are composed of tandemly ordered repetitive DNA. Previous studies have
      suggested that the exchanges between acrocentric chromosomes have resulted in
      concerted evolution of different DNA sequences in their short arms. The
      acrocentric chromosomes are clinically relevant since they are involved in
      Robertsonian translocation formation and non-disjunction resulting in aneuploidy.
      Here we have identified seven new satellite III repetitive DNA subfamilies,
      determined their nucleotide sequences and established their chromosomal
      distributions on the short arms of the acrocentric chromosomes. Knowledge of
      these related sequences may help to elucidate the molecular basis of Robertsonian
      translocation formation.

PMID- 11330398
TI  - Satellite III sequences on 14p and their relevance to Robertsonian translocation
      formation.
AB  - Robertsonian translocations (ROBs) are the most common rearrangements in humans,
      contributing significantly to genetic imbalance, fetal wastage, mental
      retardation and birth defects. Rob(14q21q) and rob(13q14q), which are formed
      predominantly during female meiosis, comprise the majority (approximately 85%) of
      all ROBs. Previous studies have shown that the breakpoints are consistently
      located within specific regions of the proximal short arms of chromosomes 13, 14,
      and 21. The high prevalence of these translocations, the consistent breakpoints
      found, and the fact that roughly 50% of cases occur sporadically suggest that the
      sequences at or near the breakpoints confer susceptibility to chromosome
      rearrangement and that the rearrangements occur through a specific mechanism. To
      investigate this hypothesis, we developed hamster-human somatic cell hybrids
      derived from de novo rob(14q21q) patients that contained the translocated
      chromosome segregated from the other acrocentric chromosomes. We determined the
      physical order of five satellite III subfamilies on 14p, and investigated their
      involvement in formation of these de novo translocations.

PMID- 11330399
TI  - Trigenomic origin of the hexaploid Psammopyrum athericum (Triticeae: Poaceae)
      revealed by in-situ hybridization.
AB  - The genomic constitution of the hexaploid Psammopyrum athericum was studied with
      in-situ DNA hybridization using both genomic DNA and isolated cloned sequences as
      probes. A genomic probe from Thinopyrum bessarabicum (E genome) hybridized
      successfully to 14 chromosomes of Ps. athericum and a probe from Festucopsis
      serpentinii (L genome) hybridized to another 14 chromosomes. The remaining
      chromosomes did not hybridize, apart from in the centromeric region, to any of
      the genomic probes used. It is thus proposed that Ps. athericum contains the
      genomes E, L and X where X stands for a so-far unknown genome. Psammopyrum
      athericum has three pairs of pTa71 sites and approximately 30 pSc119:2 sites. The
      origin of the third genome will be a matter for further research using genomic
      and genome-specific probes.

PMID- 11330401
TI  - Mapping of 31 horse genes in BACs by FISH.

PMID- 11330400
TI  - Chromosomal painting detects non-random chromosome arrangement in dasyurid
      marsupial sperm.
AB  - Chromosome arrangements have been studied in metaphase and interphase somatic
      cells and in sperm of many animal species, but there are conflicting data and it
      is still not clear whether chromosomes are arranged randomly or non-randomly. We
      used chromosome painting to reveal the positions of chromosomes in marsupial
      sperm. Marsupials are ideally suited for these studies because they have only a
      few large chromosomes. Here, we show that chromosomes occupy fixed positions in
      the immature and mature sperm of Sminthopsis crassicaudata. We suggest that the
      non-random arrangement of chromosomes in marsupial sperm may be important in
      establishing chromosome arrangement and patterns of gene activity within the
      developing embryo.

PMID- 11330402
TI  - Postprandial improvement of gastric dysrhythmias in patients with type II
      diabetes: identification of responders and nonresponders.
AB  - Using the technique known as electrogastrography, we studied the postprandial
      response of gastric myoelectrial activity in subjects with type II diabetes.
      Seventy-one subjects with type II diabetes underwent 1 hr of fasting
      electrogastrography recording. HbA1c and fasting serum glucose levels were
      obtained. Subjects then underwent an additional 2 hr of electrogastrography
      recording in the post prandial state. Sixty of the 71 patients (85%) had gastric
      rhythm abnormalities in the fasting state. Forty-six of 71 subjects (65%)
      responded to the test meal by improving their electrogastrography tracings
      (responders) while 35% did not respond (nonresponders). The time spent in
      bradygastria during the fasting state by responders was 26.3+/-12.8% vs 10.9+/
      8.5% for nonresponders (P < 0.0001). The percent tachygastria during the fasting
      state in responders was 19.8+/-13.0%, which was less than nonresponders (38.3+/
      29.7%) (P < 0.001). Fasting plasma glucose and HbA1c could not be used to predict
      the gastric myoelectrical response to meal. In conclusion, gastric rhythm
      disturbances are common in type II diabetes; there was no correlation between
      HbA1c levels, age, duration of diabetes, or fasting serum glucose and gastric
      dysrhythmia in response to meal; two groups of subjects emerged: those who became
      less dysrhythmic in the post pradial state (responders) and those who did not
      (non-responders); and fasting bradygastria was associated with responders and
      fasting tachygastria was associated with nonresponders.

PMID- 11330403
TI  - Postprandial blood glucose latency after oatmeal is a valid screening test for
      diabetic gastropathy in type 1 diabetes, but not in type 2 diabetes.
AB  - Disordered gastric motility occurs frequently in diabetes mellitus. Gastric
      emptying time is abnormal in about 50% of diabetic patients and delayed emptying
      time is known as an important cause for brittle diabetes in type 1 diabetes. We
      compared the rise in blood glucose after a standardized meal (oatmeal test) as a
      noninvasive screening test for diabetic gastropathy with the noninvasive
      measurement of gastric emptying time with ultrasound in type 1 and type 2
      diabetic patients. The test result was considered pathological if the rise of
      blood glucose after an initial steady state did not reach 20 mg/dl in the first
      20 min after the meal (prolonged blood glucose latency). We found a sensitivity
      of 90% (58.7-99.8) and a specificity of 100% (71.5-100) for the oatmeal test in
      type 1 diabetes in the gastropathy screening. In type 2 diabetes we found a
      sensitivity of 13% (1.5-38.3) and a specificity of 78% (60-90.7) (95% CI). In
      conclusion, the oatmeal test seemed to be a good, noninvasive screening test in
      diabetic gastropathy in type 1 diabetes, but has no diagnostic value in type 2
      diabetes. The causes for such a difference may be due to a different postprandial
      blood glucose regulation in type 2 diabetes compared to the beta-cell-depleted
      type 1 diabetes.

PMID- 11330404
TI  - Proximal stomach function in systemic sclerosis: relationship with autonomic
      nerve function.
AB  - Gastrointestinal involvement is frequent in patients with systemic sclerosis
      (SSc); however, studies on the proximal stomach and its regulation are lacking.
      It has been hypothesized that the primary event in the pathogenesis of
      gastrointestinal involvement in SSc is an early neural lesion. This study
      investigates proximal stomach function and its relation to autonomic nerve
      function in SSc. Twenty SSc patients classified in to clinical subsets, underwent
      measurement of proximal stomach function with and without glucagon by electronic
      barostat and an assessment of autonomic nerve function. SSc patients were not
      significantly different from 11 controls for gastric compliance (59.5+/-5.0 vs
      47.7+/-4.2 ml/mm Hg, P = 0.1). The pressure-volume curves in each participant
      with and without glucagon were significantly different (P < 0.001). A significant
      positive association was found between gastric compliance and autonomic nerve
      function (P < 0.05). The change in gastric compliance during glucagon
      administration was significant-associated with autonomic function (P < 0.05). The
      perception cumulative scores did not differ between SSc patients and control
      subjects (P = 0.2). In conclusion, proximal stomach function is associated with
      autonomic nerve function in SSc patients. This confirms the frequent association
      of motility disorders with autonomic dysfunction in SSc.

PMID- 11330405
TI  - Comparison of ileoanal pouch and rectal function measured by barostat.
AB  - The aim of this study was to compare pouch and rectal sensory and motor
      characteristics and to assess the influence of a meal on pouch tone and motility.
      Fifteen patients with an ileoanal J-pouch, with adequate pouch function and 12
      healthy controls were studied. Visceral compliance was assessed using an
      electronic barostat by a pressure distension procedure, during which also
      sensitivity was scored by visual analog scales (VAS). The response to a meal was
      assessed during set pressure. Pouch and rectal compliance were not significantly
      different (9.3+/-0.7 vs 10.6+/-1.1 ml/mm Hg). VAS score for urge at 28 mm Hg was
      reduced in patients: 2.4+/-0.5 cm vs 4.7+/-0.9 cm in controls (P < 0.05). The
      postprandial decrease in intra-bag volume was more pronounced in patients (44+/
      11%) than in controls (9+/-6%, P < 0.01). Postprandial phasic contractions were
      also more pronounced in patients. In conclusion, compliance is not significantly
      different between ileoanal pouch and rectum; differences in sensitivity reach
      significance only at high pressure. Significant differences were especially
      observed in the postprandial state with an increase in tone and frequency of
      phasic contractions in pouch patients.

PMID- 11330406
TI  - Prevalence of gastric myoelectrical abnormalities in patients with nonulcer
      dyspepsia and H. pylori infection: resolution after H. pylori eradication.
AB  - The aims of this study were to investigate the effects of H. pylori eradication
      on gastric myoelectrical activity and dyspeptic symptoms. Sixty-two subjects with
      H. pylori infection and no active peptic ulcer participated in this study, which
      involved three sessions. Anti-H. pylori therapy consisting of clarithromycin and
      omeprazole was given for two weeks. Gastric myoelectrical activity was measured
      using surface electrogastrography and dyspeptic symptoms were scored at each
      session. A [14C] urea breath test was performed at baseline and one month after
      treatment. In comparison with baseline, the percentage of normal slow waves was
      significantly increased and the mean total symptom score was significantly
      reduced one and three months after therapy (P < 0.05). Approximately 40% of
      patients with nonulcer dyspepsia' symptoms and H. pylori infection have abnormal
      gastric myoelectrical activity, which may be normalized following the eradication
      of H. pylori infection. The normalization of gastric myoelectrical activity may
      be one explanation for the significant symptom improvement in this subset of the
      dyspepsia population after H. pylori eradication.

PMID- 11330407
TI  - Pharmacological and dietary prophylaxis and treatment of acute actinic
      esophagitis during mediastinal radiotherapy.
AB  - Our purpose was to evaluate a pharmacological and dietary protocol of prophylaxis
      and treatment of acute actinic esophagitis during mediastinal radiotherapy. This
      phase II study was conducted on 29 patients affected by cancer not directly
      involving the esophagus. The irradiated volume included at least 10 cm of
      esophagus with a median dose of 46 Gy and the incidence of clinical acute
      esophagitis was scored with RTOG-EORTC tables. During the entire course of
      radiation therapy all patients were subjected to prophylaxis pharmacological
      therapy in addition to dietetic rules commonly used. All patients were evaluable,
      9 (31%) had no acute esophageal toxicity, 20 (69%) had toxicity of degree 1, and
      no patient showed a toxicity of degree 2, 3, or 4, there were no toxicity-related
      related interruptions of the radiotherapy course. In conclusion, this low cost
      protocol seems to reduce the incidence and degree of acute radiation esophagitis
      (without added morbidity), compared with literature reports.

PMID- 11330408
TI  - Effect of resistant starch on potential biomarkers for colonic cancer risk in
      patients with colonic adenomas: a controlled trial.
AB  - Resistant starch decreases the concentration of secondary bile acids in the feces
      and the proliferation rate of colonic mucosal cells in healthy volunteers. This
      may reduce the risk of colon cancer. We investigated 23 patients with recently
      removed colonic adenoma(s) in a controlled parallel trial. They consumed 45 g of
      maltodextrin per day as placebo for four weeks and were randomly assigned to
      either 45 g of native amylomaize starch, containing 28 g of resistant starch type
      II or 45 g of maltodextrin for another four weeks. No effect on colorectal cell
      proliferation, fecal wet and dry weights, pH, and short-chain fatty acid
      excretion was seen. The bile acid concentration in fecal water decreased by 15%
      (P = 0.048) and the percentage secondary bile acids decreased by 14% (P = 0.002)
      on resistant starch relative to placebo. Whether this has a substantial role in
      colon cancer prevention in these patients remains to be established.

PMID- 11330409
TI  - 8-Cl-adenosine induces differentiation in LS174T cells.
AB  - 8-Cl-adenosine represents a novel nontoxic chemotherapeutic agent shown to
      inhibit growth of a number of colorectal cancer cell lines. We have utilized the
      mucin-secreting colorectal cancer cell line, LS174T, to assess the growth
      inhibitory properties of 8-Cl-adenosine independent of its parental compound, 8
      Cl-cAMP. Conversion of 8-Cl-cAMP to 8-Cl-adenosine is required for growth
      inhibition in LS174T cells. 8-Cl-Adenosine inhibited growth by inducing a G1 cell
      cycle arrest that was associated with large (eightfold) increases in p21WAF1/Cip1
      and p53 protein levels and a decrease in the phosphorylation status of the
      retinoblastoma protein. LS174T cells did not undergo apoptosis. In addition, 8-Cl
      adenosine also induced some degree of enterocytic differentiation. Both villin
      protein levels as well as alkaline phosphatase activity rose (2- and 3.5-fold,
      respectively) in response to treatment with 8-Cl-adenosine. Our results suggest
      that in LS174T cells, 8-Cl-adenosine not only serves as a growth inhibitory agent
      but also as an inducer of enterocytic differentiation.

PMID- 11330410
TI  - Distribution and properties of neutral ceramidase activity in rat intestinal
      tract.
AB  - Ceramide plays an important role in regulating cell proliferation and apoptosis.
      Recent studies indicate that generation of ceramide in the intestine from
      sphingomyelin hydrolysis may be implicated in colon cancer development. The
      enzymes that catalyze the further hydrolysis of ceramide in the intestine have,
      however, not been well investigated. Our data reveal the existence of a
      ceramidase (EC 3.5.1.23) in rat intestinal mucosa with an optimal pH of 7.0. One
      milligram of mucosal protein is able to hydrolyze 44.0+/-9.6 nmol of ceramide in
      1 hr. The activity is low in the proximal duodenum and increases to a plateau in
      the proximal jejunum. The activity is then similar throughout the small
      intestine, until it declines in the distal part of ileum. Some activity is also
      detectable in the colon. The activity increases slightly in the presence of
      monomeric bile salt concentrations and sharply at the critical micellar
      concentration. Similar patterns were observed for both primary (taurocholate) and
      secondary (taurodeoxycholate) bile salts. The addition of Triton X-100 enhances
      the ceramidase activity at optimal bile salt concentration. The reaction is
      linear with time for the first 20 min and the hydrolytic rate declines slowly
      thereafter. Finally, the activity shows a considerable resistance against tryptic
      degradation, as 71% of the ceramidase activity remained when the homogenates were
      preincubated with high concentrations of trypsin. Intestinal mucosa also has a
      ceramide synthesis activity, with a distribution pattern generally paralleling
      ceramide hydrolysis activity. In conclusion, intestinal neutral ceramidase has a
      distinct distribution pattern and bile salt dependence, which enables it to
      collaborate with intestinal sphingomyelinase in hydrolysis of sphingomyelin.

PMID- 11330411
TI  - Porcelain gallbladder and cholangiocarcinoma with anomalous pancreaticobiliary
      union.

PMID- 11330412
TI  - Superficial spreading carcinoma involving the whole esophagus.

PMID- 11330413
TI  - Gastrointestinal damage induced by celecoxib and rofecoxib in rats.
AB  - Five experimental models were developed in different groups of Wistar rats (N =
      15) to study selective COX-2-inhibitor NSAIDs such as celecoxib and rofecoxib, as
      follows: (1) dose-dependent oral Celecoxib and Rofecoxib for 5 days, and 24 hr
      after oral indomethacin; (2) Same as 1 but subcutaneously; (3) gastric ulcer
      induced by glacial acetic acid; (4) duodenal ulcer induced by cysteamine; and (5)
      stress by immobilization and immersion in water at 15 degrees C for 6 hr.
      Celecoxib and Rofecoxib, either orally or subcutaneously, did not produce
      necrotic lesions in healthy gastrointestinal mucosa (0%), showing normal
      histology. In contrast, previously indomethacin-induced lesions were aggravated
      (90%, P < 0.001). Total necrosis in the small intestine as well as increased
      ulcers and perforation of gastric and duodenal ulcers induced by acetic acid and
      cysteamine were observed. There was also aggravation of the necrotic gastric area
      in stress (60-90%, P < 0.05). Celecoxib and rofecoxib showed neutrophilia
      (5000/mm3) similar to that with indomethacin. In contrast, there was no leukocyte
      infiltration in the gastric mucosa; thus, we can consider it a selective COX-2
      NSAID. In conclusion, celecoxib and rofecoxib at doses causing COX-2 but not COX
      1 inhibition did not produce toxic lesions in healthy gastrointestinal mucosa,
      yielding a broad therapeutic margin. In contrast, when administered in altered
      gastrointestinal mucosa, they aggravated and complicated gastric ulcers as well
      as necrosis in the small intestine, consequently restricting their clinical use.

PMID- 11330414
TI  - Cyclooxygenase-2 expression in Barrett's esophagus.
AB  - Barrett's epithelium is a recognized premalignant condition for esophageal
      adenocarcinoma. Nonsteroidal antiinflammatory drugs (NSAIDs) decrease the
      relative risk of colon cancer in humans and the esophageal tumor load in
      carcinogen-treated mice. Previous studies provided conflicting results for COX-2
      activity in Barrett's mucosa. Pinch mucosal biopsies were collected from
      Barrett's and adjacent normal esophageal mucosa from 17 patients with Barrett's
      esophagus. Low-grade dysplasia was found in seven patients. COX-2 protein was
      undetectable in normal esophageal mucosa. COX-1 protein expression did not vary
      between normal and Barrett's epithelium. Increased COX-2 protein was detected in
      Barrett's epithelium in seven patients (41%) but did not differ with or without
      dysplasia (43% vs 40%). In conclusion, COX-2 protein is increased in 41% of
      patients with Barrett's epithelium compared to normal esophageal mucosa but did
      not differ with or without dysplasia. COX-2 induction may be an early event in
      the development of Barrett's esophagus.

PMID- 11330415
TI  - Objective assessment of cognitive factors involved in visceral perception by
      using event-related cerebral evoked responses to esophageal target stimulation in
      man.
AB  - Evoked potential (EP) studies provide an objective measure of the neural pathways
      involved with perception of gastrointestinal stimulation. The effects of
      cognitive factors, such as anticipation or awareness, on EP responses are not
      known. We compared the EP response to esophageal electrical stimulation with the
      cortical activity associated with target detection and anticipation of the same
      stimulus. In 12 healthy men (26.8+/-6 years old), esophageal electrical
      stimulation (0.2 Hz, 0.2 msec, 15 mA) was applied, and the EP recorded using
      scalp electrodes. A computerized model of randomly applied target stimuli (1:5
      ratio) was used to separately record the EP associated with stimulation and the
      event-related cognitive EP associated with a dual task-related or anticipated
      stimulation approach. A periodic electrical stimulus represented the nontarget
      stimulus and a second electrical impulse (oddball model) or an omitted stimulus
      (anticipatory model) the target stimulus. The event-related cognitive EP
      responses were also compared with standard and anticipatory auditory P300 evoked
      potentials. The esophageal and auditory oddball stimulus approach elicited event
      related P300EP in all subjects. P300EP associated with electrical stimulation had
      a longer peak latency (P < 0.0001) and smaller amplitude than those obtained with
      auditory stimulation. Anticipatory evoked potentials could be obtained by
      electrical skipped stimulation in 8 of 12 subjects. These EP were similar to
      those obtained with omitted auditory target stimulation, although of
      significantly smaller amplitude than auditory standard P300EP (P < 0.001). In
      conclusion, the brain response associated with directed effortful processing of
      discriminate esophageal stimuli consists of a large event-related potential
      (P300EP). Anticipatory stimulation produces a similar event-related cortical
      response, which is associated with attention to and awareness of the actual
      stimulus. The P300EP to gastrointestinal stimuli may provide an objective and
      powerful electrophysiological tool for the assessment of the cognitive factors
      associated with visceral perception.

PMID- 11330416
TI  - Impairment of deglutition reflex by acid-induced esophageal mucosal injury.
AB  - Swallowing is an important defense mechanism against reflux esophagitis as it
      helps clear refluxed gastric contents from the esophagus, while bicarbonate in
      the saliva acts to neutralize acid. The purpose of the present study was to
      examine the effect of esophagitis on the deglutition reflex in anesthetized
      opossums. Animals perfused with either an acidified pepsin solution for 45 min or
      with 100 mM hydrochloric acid for 45 min on each of three consecutive days
      exhibited a significantly impaired deglutition reflex in comparison to baseline.
      Control animals perfused with 0.9% saline showed no impairment. Bilateral
      cervical vagotomy in animals perfused with acidified pepsin attenuated the
      impaired deglutition reflex. Taken together, these results suggest that
      esophagitis causes an impairment in the deglutition reflex that is mediated by
      vagal afferent pathways.

PMID- 11330417
TI  - Increased taurine content in esophageal mucosa of children affected by
      gastroesophageal reflux.
AB  - We studied the possible involvement of mucosal amino acid metabolism in the
      pathogenesis of gastroesophageal reflux disease in children. Eighteen children
      with gastroesophageal reflux disease (8 with reflux esophagitis and 10 without)
      and 10 children with normal 24-h esophageal pH monitoring as a comparative group
      underwent esophagogastroduodenoscopy with biopsies. Plasma and esophageal mucosa
      amino acids were assayed by liquid chromatography. In children affected by
      gastroesophageal reflux disease we found an increase of mucosal taurine (P <
      0.01) and a decrease of serine (P < 0.01). No differences were noted between
      patients with and without esophagitis. Significant positive correlations (P <
      0.001; r = 0.626) were found between mucosal taurine content and reflux index.
      Plasma amino acid concentrations did not show any significant differences among
      groups. Our results indicate that biochemical alterations precede the
      histological findings of inflammation, likely reflecting the adaptive response of
      the esophageal mucosa to the gastric contents exposure.

PMID- 11330418
TI  - Transient lower esophageal sphincter relaxations and gastroesophageal reflux
      episodes in healthy subjects and GERD patients during 24 hours.
AB  - Still little is known about the 24-hr pattern of transient lower esophageal
      sphincter relaxations (TLESRs), particularly in patients with GERD. The aim of
      our study was to evaluate the 24-hr esophageal and LES motor pattern and
      esophageal pH and to identify the relationship between TLESRs and
      gastroesophageal reflux in healthy subjects and in GERD patients. Ten healthy
      subjects and nine patients with esophagitis (grade I-II) underwent a 24-hr pH
      manometric recording by means of a portable electronic device. The recording
      aimed at identifying the temporal relationships between reflux episodes and LES
      motor events. The GERD patients showed a greater number of either reflux episodes
      or TLESRs during the 24 hr as compared to controls. While most refluxes occurred
      during TLESRs in both groups, a small percentage of TLESRs was followed by reflux
      episodes in healthy people, with only a slight increase in GERD patients. In
      conclusion, although representing an important motor pattern during
      gastroesophageal reflux both in healthy subjects and in patients with GERD, TLESR
      could probably be considered one of the pathophysiologic mechanisms of
      gastroesophageal reflux more than the primary cause of reflux episodes.

PMID- 11330419
TI  - Role of nitric oxide during swallow-induced esophageal shortening in cats.
AB  - Swallowing induces esophageal shortening due to contraction of the longitudinal
      muscle (LM) layer. Experiments in the opossum have shown an excitatory effect of
      nitric oxide (NO) on esophageal LM strips. We evaluated the role of NO in swallow
      induced esophageal shortening and assessed the effect of NO in vitro on feline LM
      strips. Swallow-induced esophageal shortening was studied before and after NO
      synthase blockade with L-NAME. In five cats esophageal shortening was measured
      using two endoscopically affixed mucosal clips. In another five cats LM
      contraction was measured by a strain gauge sutured on the serosal side at 2 cm
      above the LES; muscle strips from that region were obtained for in vitro studies.
      Swallowing induced esophageal shortening of 48.3+/-8.3% and LM contraction of
      4.4+/-0.8 g in the control period and 32.1+/-8% and 3.0+/-0.4 g after L-NAME (P <
      0.05). Nitric oxide and SNP did not change the basal tone of esophageal LM strips
      but provoked inhibition of metacholine-induced tonic and phasic activity.
      Electrical field stimulation induced frequency-dependent contractions that were
      reduced by atropine without further reduction after L-NAME. In conclusion, the
      reduction of esophageal shortening after L-NAME during the in vivo experiments
      suggested an excitatory effect of NO on the feline esophagus. The in vitro
      experiments, however, showed no contractile effect of NO or SNP on LM strips, but
      an inhibitory effect on the precontracted tissue. The influence of NO synthase
      blockade on in vivo esophageal LM shortening might be secondary to its effect on
      circular muscle contractility.

PMID- 11330420
TI  - Cyclic vomiting syndrome: in vitro nitric oxide and interleukin-6 release by
      esophageal and gastric mucosa.
AB  - Cyclic vomiting syndrome is a disorder characterized by recurrent episodes of
      nausea and vomiting with complete resolution of symptoms between attacks. Nitric
      oxide plays a critical role in regulating several components of gastrointestinal
      mucosal defense and injury. Interleukin-6 has a wide variety of actions in the
      gastrointestinal apparatus. The purpose of this study was to evaluate the
      synthesis and release of nitric oxide and interleukin-6 by the esophageal and
      gastric mucosa in 10 children with cyclic vomiting syndrome, during symptom-free
      periods, and in 10 controls. The nitric oxide and interleukin-6 release by
      esophageal mucosa cells obtained from cyclic vomiting patients was quite similar
      to that in controls, but the release of nitric oxide from gastric mucosa cells of
      patients was significantly higher than that of controls. Conversely, no
      interleukin-6 was detectable in gastric mucosa cell supernatants in any of the
      patients. Further studies are needed to evaluate the relationship between factors
      triggering cyclic vomiting syndrome and the release of nitric oxide and
      interleukin-6 by gastric mucosa.

PMID- 11330421
TI  - Increased oxidative and nitrative stress in human stomach associated with cagA+
      Helicobacter pylori infection and inflammation.
AB  - In order to study the role of Helicobacter pylori infection in gastric
      carcinogenesis, we have measured oxidized (carbonyls) and nitrated (nitrotyrosine
      containing) proteins as markers for oxidative and nitrative stress in 216 human
      gastric biopsies using dot and western immunoblots and correlated the results
      with H. pylori, cagA status, expression of interleukin-8 and inducible nitric
      oxide synthase (iNOS) mRNAs, and gastric pathology. Higher levels of both
      oxidized and nitrated proteins were found in patients with either chronic
      gastritis or duodenal ulcer than in those with normal mucosa. The levels of
      modified proteins were significantly higher in inflamed samples infected with H.
      pylori, especially cagA+ strains, and in those with expression of interleukin-8
      and iNOS mRNAs than in those negative for these parameters. These results
      indicate that infection with cagA+ H. pylori induces significant oxidative and
      nitrative stress in stomach mucosa, contributing to the pathogenesis of H. pylori
      associated gastroduodenal diseases.

PMID- 11330422
TI  - Effects of polaprezinc on lipid peroxidation, neutrophil accumulation, and TNF
      alpha expression in rats with aspirin-induced gastric mucosal injury.
AB  - We examined the roles of lipid peroxidation, neutrophil accumulation, and
      inflammatory cytokines in the protective effect of polaprezinc against aspirin
      induced gastric mucosal injury in rats. The intragastric administration of
      acidified aspirin induced hyperemia and hemorrhagic erosions in rat stomachs. The
      increase in the total gastric erosive area after aspirin administration was
      significantly inhibited in a dose-dependent manner by treatment with polaprezinc.
      The increases in thiobarbituric acid-reactive substances and tissue-associated
      myeloperoxidase activity 3 hr after aspirin administration were significantly
      inhibited by pretreatment with polaprezinc. The gastric concentration of TNF
      alpha increased after aspirin administration, and the increase was also inhibited
      in a dose-dependent manner by treatment with polaprezinc. The peak expression of
      TNF-alpha mRNA 1 hr after aspirin administration was inhibited by 30 mg/kg of
      polaprezinc. Based on these data, the beneficial effects of polaprezinc on
      aspirin-induced gastric mucosal injury may be attributed to its antioxidative and
      antiinflammatory properties.

PMID- 11330423
TI  - Spontaneous gastric rupture and hemoperitoneum due to gastric hemangioma.

PMID- 11330424
TI  - Prospective trial evaluating early initiation of feeding in patients with newly
      placed one-step button gastrostomy devices.
AB  - The purpose of this study was to prospectively assess the feasibility and safety
      of early feeding in patients with newly placed one-step button (OSB) gastrostomy
      devices. Twenty-five patients who underwent percutaneous endoscopic button
      gastrostomy placement were prospectively enrolled. The patients underwent
      radiographic assessment (Gastrografin gastrograms) 3 hr after gastrostomy
      placement. Contrast extravasation was not documented in any patient. Aside from
      one patient who aspirated the contrast solution after the radiologic study, all
      others (96%) were successfully fed on the day the gastrostomy buttons were
      placed. In this prospective study of patients with newly placed OSB gastrostomy
      devices, early initiation of feeding was feasible and safe. In a fashion similar
      to their tube-style counterparts, button gastrostomy devices provide adequate
      apposition between the stomach and abdominal wall immediately after their initial
      placement.

PMID- 11330425
TI  - Cholecystokinin (CCK) secretion in patients with severe short bowel syndrome
      (SSBS).
AB  - This study examined the effects of a liquid meal on cholecystokinin (CCK)
      secretion in patients with severe short bowel syndrome (SSBS) receiving home
      total parenteral nutrition (TPN) support for 5-19 years after massive small bowel
      resection. Five patients with SSBS due to superior mesenteric artery or vein
      thrombosis were included. Five healthy volunteers served as controls. Blood was
      drawn before and 1 hr following consumption of 250 ml of a liquid diet containing
      232 kcal with 8 g fat and 8 g protein. Plasma CCK activity was evaluated by
      amylase bioassay. All patients had stable weight with a normal BMI and serum
      albumin level, although there were mild abnormalities in their liver function
      tests. CCK secretion after stimulation was significantly decreased in patients.
      These results suggest that reduction in intestinal length influences CCK
      secretion in response to meal stimulation in SSBS patients.

PMID- 11330426
TI  - Does better disease-related education improve quality of life? A survey of IBD
      patients.
AB  - The importance of health-related quality of life (HRQOL) assessment in patients
      with chronic disorders such as inflammatory bowel disease (IBD) is now
      acknowledged by researchers. Of the many factors that may influence HRQOL,
      patient knowledge of the condition and disease-related information provision have
      hitherto not been studied. In all, 250 patients with inactive IBD (UC = 128, CD =
      122) were randomly chosen from our IBD clinic. Two sets of questionnaires
      [initially a standard questionnaire to assess level of disease-related
      information by a patient information score (PIS), followed by a HRQOL
      questionnaire] were sent to each patient. In the PIS, a score of 7 or more
      indicated satisfactory disease-related knowledge and in the HRQOL, a score less
      than 51 suggested a normal QOL, and a score above 60 significantly impaired QOL.
      A total of 168 patients (66%) returned both the questionnaires (UC = 91, CD =
      77). The mean QOL in patients with UC and CD was 62.2+/-8.3 and 63.9+/-9.5
      respectively, (P = NS). 99 patients (59%) had significantly impaired QOL (mean
      score 65+/-7.6) with only 12 patients (8%), 6 in each group, having a normal QOL.
      Mean PIS score for the patients was 7.04+/-0.1; 53% of the UC patients and 75% of
      the CD patients (P = 0.006) were considered well informed (ie, PIS scores of 7 or
      more). The mean PIS for UC patients was 6.5+/-0.4 vs 7.5+/-0.2 for the CD group
      (P = 0.001). There was, however, no correlation seen between the QOL and PIS
      scores, both for UC and CD patients (R = 0.3). In conclusion, most patients with
      IBD have impaired QOL, despite of having inactive disease. The level of disease
      related knowledge appears to be better in patients with CD, although that does
      not seem to affect QOL.

PMID- 11330427
TI  - Diagnostic value of DNA image cytometry in ulcerative colitis.
AB  - The increased risk of colorectal cancer in patients with extensive, long-standing
      ulcerative colitis is well established. The interpretation of dysplasia as the
      common precursor lesion of colorectal cancer in ulcerative colitis is, however,
      subject to inter- and intraobserver variation. The histologic diagnosis is
      particularly difficult in the presence of acute inflammation. Therefore, the
      analysis of ploidy patterns might be a more objective diagnostic tool. In the
      present study, the correlation of ploidy and dysplasia of the colonic mucosa was
      evaluated in the absence and presence of inflammation. Image cytometry was
      performed on 561 fixed, paraffin-embedded tissue specimens from 67 patients with
      ulcerative colitis. Twenty patients had long-standing and extensive disease,
      including eight patients in whom the colitis was associated with colorectal
      cancer. Dysplasia was only found in patients with long-standing colitis or with
      colorectal cancer and was significantly more often diagnosed in the case of
      concomitant inflammation. On the other hand, aneuploid patterns were shown to
      occur independent of inflammatory activity. Aneuploidy was present in all
      colorectal carcinomas associated with ulcerative colitis and in 46.2% of
      specimens with dysplasia. Moreover, aneuploidy was detectable in four of 12
      samples with low-grade dysplasia as well as in one case devoid of any dysplastic
      alteration. Ulcerative colitis patients with low-grade dysplasia plus aneuploidy
      probably represent a subgroup that might be at higher risk of developing
      colorectal cancer than patients with low-grade dysplasia alone. All in all, image
      cytometry analysis might be instrumental in identifying neoplastic lesions even
      in cases of increased inflammatory activity or regenerative change.

PMID- 11330428
TI  - Celiac disease without villous atrophy: revision of criteria called for.
AB  - Current diagnostic criteria of celiac disease require small bowel villous
      atrophy, although the damage develops gradually. We therefore searched for
      evidence of disease in 10 adults suspected to have celiac disease, but evincing
      only minor mucosal inflammation and increase in gammadelta+ cells without villous
      atrophy. Twenty untreated celiac and 27 nonceliac patients served as biopsy
      controls. CD3+, alphabeta+, and gammadelta+ cells were increased in patients with
      only minor mucosal lesions, but less than in celiac patients. The inflammation
      resolved on gluten-free diet, and abdominal symptoms were alleviated. Eight of 10
      had positive endomysial, seven gliadin, and nine tissue transglutaminase
      antibodies; all normalized on diet. Eight patients had osteopenia; HLA DQ2 was
      found in all. Minor mucosal lesions with an increase in gammadelta+
      intraepithelial lymphocytes were suggestive of celiac disease. Our patients
      showed a clinical, histological, and serological recovery on diet; risk of
      osteopenia speaks in favor of dietary treatment.

PMID- 11330429
TI  - Evidence of local eosinophil activation and altered mucosal permeability in
      collagenous colitis.
AB  - The local release of the inflammatory mediators eosinophil cationic protein and
      myeloperoxidase and the permeability marker albumin was studied in collagenous
      colitis using a new technique for segmental perfusion of the rectum and
      descending colon. Perfusion of both segments was successful in 19/25 (76%) of
      patients with collagenous colitis and controls with noninflammatory conditions.
      The concentration of myeloperoxidase was increased in the perfusion fluids from
      both segments in only one patient with collagenous colitis and in none of the
      controls. On the other hand, concentrations of eosinophil cationic protein and
      albumin in the perfusate from the rectum were significantly increased in
      collagenous colitis compared with controls, and similar trends were seen in the
      perfusates from the descending colon. Furthermore, there was a significant
      correlation between the increased concentrations of eosinophil cationic protein
      and albumin, indicating a possible relation between eosinophil activation and
      disturbed mucosal permeability in collagenous colitis.

PMID- 11330430
TI  - Pseudotumorous chronic pancreatitis associated with inflammatory bowel disease.
AB  - Chronic pancreatitis associated with inflammatory bowel disease is now considered
      as extraintestinal manifestation of that disease. The clinical and radiological
      features of the new entity are markedly different from those of chronic
      calcifying pancreatitis. We report the case of a 68-year-old man presenting with
      a pseudotumorous chronic pancreatitis associated with ulcerative colitis.
      Diagnosis was made after endoscopic retrograde cholangiopancreatography (ERCP)
      and cytological analysis of stenosis brushings and was confirmed by the clinical
      evolution. Existence of IBD-associated pancreatitis with pseudotumorous features
      has to be taken into account in order to avoid inappropriate pancreatic
      resection.

PMID- 11330431
TI  - Combination therapy of active HBsAg vaccination and interferon-alpha in
      interferon-alpha nonresponders with chronic hepatitis B.
AB  - Treatment with interferon-alpha leads to cessation of viral replication in 30-40%
      of patients with chronic hepatitis B. Preliminary data suggest that therapeutic
      vaccination in patients with chronic HBV infection may be beneficial. The present
      trial was conducted to assess the efficacy of combination therapy of interferon
      alpha with HBsAg vaccination in patients who previously failed to respond to
      interferon-alpha alone. Eighteen patients positive for HBsAg and HBeAg were
      included. Mean ALT was 81+/-23 units/liter and 7 (39%) patients had HBV-DNA
      levels >2000 pg/ml. Patients received 5 million IU interferon-alpha 2b (Intron A)
      thrice weekly for six months and recombinant HBsAg (Gen H-B-Vax) at the beginning
      and 4 and 12 weeks after initiation of interferon therapy. No serious side
      effects were seen during the trial period. Loss of HBeAg was seen in 39% (7/18),
      HBV DNA was undetectable in 50% (9/18), and ALT was normal in 56% 10/18) of
      patients six months after completion of therapy. Simultaneous administration of
      interferon-a and HBsAg vaccination in patients previously not responding to
      interferon alone appears to be safe, well-tolerated, and it achieved response
      rates similar to or even higher than interferon in treatment naive patients. This
      combination therapy seems to offer a new and promising approach for patients with
      chronic hepatitis B virus infection.

PMID- 11330432
TI  - Immediate-early protooncogene expression and liver function following various
      extents of partial hepatectomy in the rat.
AB  - Immediate-early protooncogenes (IEP) are thought to play an important role in
      hepatocyte replication. Whether the extent of their expression correlates with
      the strength of the proliferative stimulus and subsequent regenerative activity
      has yet to be documented in vivo. Data are also lacking with respect to the level
      at which liver disease is associated with biochemical evidence of hepatic
      dysfunction. Thus, the objectives of this study were to determine whether a
      correlation exists between IEP gene mRNA expression and varying extents of
      partial hepatectomy (PHx) and to document the extent of resection required to
      result in increases in serum bilirubin levels. Eighty-nine adult, male Sprague
      Dawley rats underwent either sham surgery or 20%, 35%, 55%, 70% or 90% PHx.
      Postoperatively, rats were killed (N = 3-6/group) at 15 and 30 mins and 8 and 24
      hrs for c-fos, c-jun, and c-myc mRNA expression by northern blot analyses. Rats
      killed at 24 hrs also had hepatic regenerative activity documented by
      [3H]thymidine incorporation into hepatic DNA and serum bilirubin determinations.
      While c-fos mRNA expression at 15 mins and c-myc mRNA expression at 8 hrs after
      PHx did not correlate with the extent of PHx (r2 = 0.478 and 0.018,
      respectively), a weak correlation existed between c-jun mRNA expression at 30
      mins and the extent of PHx (r2 = 0.662, P < 0.05). In terms of IEP mRNA
      expression and hepatic regenerative activity, a strong correlation existed
      between c-fos mRNA expression and [3H]thymidine incorporation (r2 = 0.851, P <
      0.01) but not c-jun or c-myc mRNA expression. Compared to sham operated controls,
      [3H]thymidine incorporation was 2.0x, 3.4x, 3.2x, 7.8x, and 2.2x increased
      following 20%, 35%, 55%, 70%, and 90% PHx, respectively. Serum bilirubin levels
      remained unchanged until 70% PHx, when they increased from baseline values of
      0.54+/-0.05 mg/dl to 1.02+/-0.15 mg/dl (P < 0.05). A further increase occurred
      following 90% PHx (1.83+/-0.30 mg/dl, P < 0.01). In conclusion these findings
      indicate that c-fos mRNA expression 15 mins after PHx correlates with hepatic
      regenerative activity but not the strength of the regenerative stimulus and that
      hepatic parenchymal loss of 55-70% must occur prior to the detection of elevated
      serum bilirubin levels. The results also indicate that relative to a 70% PHx, 90%
      PHx is associated with decreased rather than increased hepatic regenerative
      activity.

PMID- 11330433
TI  - Esophageal variceal ligation for esophageal variceal hemorrhage in a patient with
      portal and primary pulmonary hypertension complicating myelofibrosis.

PMID- 11330434
TI  - Uric acid nephrolithiasis associated with interferon and ribavirin treatment of
      hepatitis C.

PMID- 11330435
TI  - Trovafloxacin hepatotoxicity.
AB  - A 19-year-old woman was treated for recurrent sinusitis with oral trovafloxacin
      and developed acute hepatitis and peripheral eosinophilia, with
      hepatosplenomegaly and ascites. Laparoscopic liver biopsy showed extensive
      centrilobular hepatocyte necrosis, likely causing venooclusive disease-like signs
      and symptoms. Clinical and laboratory abnormalities resolved completely after
      prolonged treatment with steroids. The temporal relationship between
      trovafloxacin and the onset of hepatitis favors this drug as a culprit.

PMID- 11330437
TI  - Differential oxidative injury in extrapancreatic tissues during experimental
      pancreatitis: modification of lung proteins by 4-hydroxynonenal.
AB  - Oxidative stress is considered to be a pathogenic factor for multisystem organ
      failure during acute pancreatitis. Infusion of 3% and 5% sodium taurocholate into
      the pancreatic duct of rats resulted in a 24-hr lethality of 8% and 82%,
      respectively. Kidney tissue showed a long-lasting significant elevation of
      malondialdehyde (lipid peroxidation). Only small amounts of this aldehyde were
      formed in the liver. In the lung malondialdehyde was increased during the first 6
      hr after pancreatitis induction. Malondialdehyde levels were not different for
      pancreatitis initiated by 3% or 5% taurocholate. Protein-bound carbonyls (protein
      oxidation) in the tissues were not significantly changed at any time point.
      However, after infusion of 5% taurocholate, lung proteins were oxidatively
      modified by the product of lipid peroxidation, 4-hydroxynonenal. Another
      parameter characteristic for pancreatitis with high lethality was the high number
      of neutrophils in the lungs. We conclude that oxidative stress is important for
      the injury of extrapancreatic tissues during pancreatitis, but survival is
      determined by the degree of systemic inflammation.

PMID- 11330436
TI  - Protective effect of melatonin on renal injury of rats induced by bile duct
      ligation.
AB  - Oxygen radicals have been implicated in the pathogenesis of renal injury induced
      by extrahepatic cholestasis. We conduct this study to investigate whether
      melatonin can have a protective effect against such injury. Either normal saline
      or gentamicin with or without melatonin was injected into rats that received
      either a bile duct ligation or a sham operation. The serum levels of
      malondialdehyde and total antioxidative activity were measured. The kidney was
      fixed for histologic scoring of renal injury. The serum malondialdehyde level was
      highest in the rats that received both bile duct ligation and gentamicin
      injection. Treatment with melatonin significantly increased the serum total
      antioxidative activity and reduced the serum malondialdehyde concentration. The
      mean score of renal injury, highest in the rats receiving bile duct ligation and
      gentamicin injection, was significantly reduced with melatonin treatment. By
      reducing the systemic oxygen radicals, supplementation with antioxidants exerts a
      protective effect on the renal injury induced by extrahepatic cholestasis.

PMID- 11330438
TI  - European Society for Quality in Healthcare: the experience of learning to work
      together in Europe.

PMID- 11330439
TI  - Health outcomes of asthma and COPD patients: the evaluation of a project to
      implement guidelines in general practice.
AB  - OBJECTIVE: To evaluate a project to implement guidelines on the management of
      patients with asthma or chronic obstructive pulmonany disease (COPD) in terms of
      the health outcomes of these patients. DESIGN: A before-and-after study of 1 year
      with a non-randomized but comparable reference group. SETTING: General practices
      in the Netherlands. STUDY PARTICIPANTS: Two-hundred and eighty patients from 14
      practices in the intervention group and 90 patients from five practices in the
      reference group (receiving usual care). INTERVENTION: The project included a
      comprehensive implementation programme, involving identification of barriers,
      documentation of the care provided, specific education, feedback on compliance
      with the guidelines, and peer review. This project has been found to bring the
      process of care more in agreement with the guidelines. MAIN OUTCOME MEASURES:
      Mean peak expiratory flow rate (PEFR) as a percentage of the predicted value,
      number of days with a diurnal variation in PEFR > or = 15%, number of days with
      respiratory symptoms (all recorded by patients for a period of 14 days), and
      perceived health status (Nottingham Health Profile). RESULTS: After 1 year, the
      intervention group showed statistically significant improvements with regard to
      the mean PEFR, the diurnal variation in PEFR, respiratory symptoms and the pain
      score of the Nottingham Health Profile. Comparing the changes within the
      intervention group with the changes within the reference group, only a positive
      effect of the intervention on the mean PEFR was found. CONCLUSION: The
      comprehensive implementation programme improved the lung function and symptoms of
      asthma and COPD patients in the intervention group. However, in comparison with a
      reference group, the positive effect on the lung function was only small.

PMID- 11330440
TI  - Underutilization of acute care settings in a tertiary care hospital.
AB  - OBJECTIVE: To estimate underutilization of acute care settings in a tertiary care
      hospital. DESIGN: A retrospective and concurrent cohort study using chart reviews
      and the Intensity of service, Severity of illness, Discharge screen for Acute
      Care (ISD-AC(R)) tool to measure appropriateness of acute care for patients who
      were receiving care in a less acute setting, as an indicator of underutilization.
      SETTING: A 450-bed tertiary care teaching hospital. STUDY PARTICIPANTS: Patients
      discharged from the emergency department, patients discharged from acute care
      inpatient units and patients in acute, non-critical care settings. INTERVENTIONS:
      None. MAIN OUTCOME MEASURES: The percentage of patients discharged from the
      emergency department who did not meet the criteria for acute care discharge
      screens; the percentage of patients discharged from an acute care inpatient unit
      who did not meet the criteria for discharge screens; and the percentage of
      patients who were in acute, non-critical care beds and who met the criteria for
      critical care. RESULTS: It was found that six out of 168 patients [3.57%; 95%
      confidence interval (CI), 1.32-7.61%] did not meet the discharge screens at the
      time of discharge from the emergency department. Four out of 156 patients (2.56%;
      95% CI, 0.70-6.43%) did not meet the discharge screens at the time of discharge
      from an acute care inpatient service and two out of 156 acute care patients
      (1.33%; 95% CI, 0.02-4.73%) who were in non-critical care beds met the criteria
      for critical care. CONCLUSION: These findings of underutilization may help to
      quantitate an unmet need in health care.

PMID- 11330441
TI  - Quality of paediatric care: application and validation of an instrument for
      measuring parent satisfaction with hospital care.
AB  - OBJECTIVE: To apply and validate an adapted version of an existing adult patient
      questionnaire in a study of parental satisfaction with paediatric care in a
      university hospital. DESIGN: A cross-sectional, anonymous questionnaire study. A
      total of 912 questionnaires were distributed to parents by hospital staff during
      a 2-week period. SETTING: A university children's hospital in Stockholm, Sweden.
      STUDY PARTICIPANTS: Six hundred and twenty-four parents whose children were
      receiving care at the hospital during a 2-week period in April of 1999. MAIN
      OUTCOME MEASURES: The 63-item questionnaire uses eight main measurement indices
      and an overall quality rating to define parental satisfaction with paediatric
      care. Measures of the instrument's reliability and validity were established by
      comparison with results of a pilot study conducted 1 year earlier on the
      paediatric departments of two regional Swedish hospitals. All measures were
      compared to reliability and validity estimates in the original patient
      questionnaire. RESULTS: A total of 624 questionnaires were returned, a response
      rate of 68%. The instrument demonstrated good reliability and validity.
      Reliability estimates for all eight indices were greater than 0.70 and consistent
      over time. Inter-index correlations were generally lower than 0.60, indicating
      index independence. Of the nine parameters measured, parents were most satisfied
      with staff attitudes, care processes and medical treatment. Parents' ratings were
      lowest for accessibility and staff work environment. CONCLUSION: This study
      presents a valid and reliable questionnaire instrument for measuring parental
      views of paediatric hospital care. The instrument measures the quality of
      paediatric care from a broader perspective than previously existing parent
      questionnaires.

PMID- 11330443
TI  - Integrating health status into the quality equation.

PMID- 11330442
TI  - The EFQM Excellence Model. German experiences with the EFQM approach in health
      care.
AB  - OBJECTIVE: To expand on previous reports by illustrating experiences German
      health services organizitions made in their assessment against the European
      Foundation for Quality Management (EFQM) Excellence Model. To provide an
      evaluation of the EFQM method compared to peer auditing and accreditation
      concepts within health care. DESIGN: To indicate the EFQM method and scoring
      system and draft the process of self-assessment in health services organizitions.
      To refer to the experiences of German health care pioneers during their early
      assessments. RESULTS: Using the EFQM approach, an organizition can earn up to
      1.000 points. More than 50% of German hospitals scored 200-300 points and not a
      single organizition achieved over 450 points. To make a comparison, the best
      score obtained in an industrial setting was between 650-750 points. In addition
      to the numbers, this report describes success factors and best practices of self
      assessments, as well as limitations, barriers and lessons learned during the
      implementation phase. CONCLUSION: The Excellence Model is a systematic quality
      management approach to gain competitive advantage. It is non-governmental, non
      financier driven, and generic enough to address health care issues. Having its
      foundation in industry, however, it is not specific enough to cover all areas
      relevant to health care. Integrating the management-smart method of self
      assessment with clinical standards as delivered by peer auditing and
      accreditation systems generates the potential to deliver excellence in health
      care.

PMID- 11330444
TI  - Completeness and accuracy of voluntary reporting to a national case registry of
      laparoscopic cholecystectomy.
AB  - OBJECTIVE: To validate completeness and accuracy of registry data reported from
      three randomly chosen departments contributing to The Danish National Registry of
      Laparoscopic Cholecystectomy, covering all departments offering chole cystectomy.
      DATA SOURCES: A total of 431 case reports representing cases of laparoscopic
      cholecystectomy in a 2-year period in three surgical departments. DESIGN:
      Comparison of case reports with reported data in The Danish National Registry of
      Laparoscopic Cholecystectomy. MAIN OUTCOME MEASURES: Rates of discrepancies,
      comparison of complication rates for cases in the registry and cases not reported
      to the registry. RESULTS: Completeness of registration was 69%, 80% and 99%
      respectively. A significantly higher degree of completeness was found in the only
      department with a formalized registration procedure. Inaccuracies were found in
      28-49% of the cases, but none regarding serious complications such as bile duct
      injury or perioperative death. CONCLUSIONS: The information in the national
      registry may be accurate if the present findings can be extrapolated to the
      remaining departments in the country. The number of non-reported cases should be
      minimized by introducing a formalized procedure of handling and forwarding
      information to the registry. Continuous validation through external visits by
      registry staff to contributing departments may also be advisable.

PMID- 11330445
TI  - Quality of care for urinary incontinence in a rehabilitation setting for patients
      with stroke. Simultaneous monitoring of process and outcome.
AB  - OBJECTIVE: To study the quality of care provided for patients with urinary
      incontinence following a stroke, by monitoring both process and outcome elements
      of care simultaneously. DESIGN: Prospective follow-up of patients (of all ages
      and of both sexes) with urinary incontinence that appeared following a stroke who
      were admitted for rehabilitation during a six 6-month period. SETTING: A ward for
      stroke rehabilitation in The Loewenstein Hospital-Rehabilitation Centre in
      Raanana, Israel. RESULTS: Thirty-seven patients with stroke and urinary
      incontinence (mean age 61 years, 68% men) were included in the study; 84% of the
      37 patients were discharged, although only 25% of them were continent. No lasting
      complications of urinary incontinence developed and there was no interference
      with rehabilitation activities. There was a correlation between incontinence and
      low score of Functional Independence Measure (FIM) on admission, being higher on
      discharge in those who became continent than in those who did not. CONCLUSIONS:
      Ward staff are aware of the potential problem of incontinence in patients with
      stroke. The problem is identified on admission and accorded adequate attention
      and care with satisfactory outcomes. The approach of monitoring process and
      outcome elements of care simultaneously in conditions that, during inpatient
      rehabilitation of patients with stroke, may endanger life, interfere with
      rehabilitation and delay functional recovery, could be a useful way to assess and
      improve the quality of care.

PMID- 11330446
TI  - Modelling strategies for reducing pharmaceutical costs in hospital.
AB  - OBJECTIVE: To describe drug utilization and cost in a large hospital and to
      compare the impact of different strategies on cost associated with drug
      prescribing. DESIGN: Retrospective data on drug utilization and cost, linked to
      patient clinical data and prescriber data from November 1998 were analyzed and
      modelled. MAIN OUTCOME MEASURES: Impact of different strategies for cost control.
      SETTING: A large hospital in Sydney, Australia. RESULTS: The mean cost of drugs
      per episode of care was 28 Australian dollars. Of all drug costs, 79% was
      incurred by medical units and 14% by surgical units. Oncology accounted for 42%
      and inpatients for 91% of drug costs. Although section-100 (S-100) drugs incurred
      a high cost (640 dollars) per episode of care, there were only 41 episodes where
      S-100 drugs (expensive, restricted drugs) were used, and the total cost of S-100
      drugs was only 3.7% of the total cost to the hospital. Antibiotics were the most
      commonly prescribed drug category, prescribed in 14% of all hospital episodes,
      and accounting for 14% of total drug costs. Anti-ulcer drugs were the next most
      costly group, accounting for 7% of total drug costs. A 20% reduction in use of
      antibiotics would save four times that (233,832 dollars pa) of a 20% reduction in
      use of S-100 drugs (61,392 dollars pa). DISCUSSION: Our study suggests that
      reducing inappropriate use of high volume drugs such as antibiotics could be more
      effective in optimising health facility drug budgets than attempts concentrating
      solely on reducing use of high cost drugs alone. Moreover our study suggests that
      systematic measurement of drug utilisation patterns is a key element of drug cost
      control strategies.

PMID- 11330447
TI  - Measuring, monitoring and reporting functional health outcomes: opportunities and
      challenges in a bold national initiative.

PMID- 11330448
TI  - The Wimpole Street principles.

PMID- 11330449
TI  - The Wimpole Street principles.

PMID- 11330450
TI  - Health outcomes. New quality measure for Medicare.
AB  - OBJECTIVE: A new measurement of health care quality for Medicare beneficiaries
      has been implemented by the Health Care Financing Administration (HCFA). This
      paper describes the program, presents baseline data and highlights associated
      issues. DESIGN: The Health Outcomes Survey (HOS) is a longitudinal cohort mail
      survey. Changes in population health status after 2 years will be evaluated on an
      individual plan level. SETTING: Two-hundred and eighty-seven US Medicare managed
      care plans. MAIN OUTCOMES MEASURES: Physical component and mental component
      summary scales derived from the SF-36. FINDINGS: Baseline data documented lower
      health status in older populations, while functional limitations and disease
      prevalence were higher. Among different plans, mean functional levels were found
      to be similar, although a few plans contained populations with exceptionally low
      levels. These data do not support the assertion that enrolees in for-profit plans
      are healthier than non-profit plans. CONCLUSIONS/IMPLICATIONS: The HOS is the
      first large-scale program to evaluate health outcomes among older Americans. HCFA
      recognizes several technical and policy issues. Technical issues include possible
      biased reporting for subpopulations, the validity of proxy responses and
      respondent burden. Policy issues concern the appropriateness of using a generic
      measure such as the SF-36 and how much change in health status can be attributed
      to quality of health care. HCFA plans to extend the HOS to beneficiaries in
      traditional Medicare. The HOS project is expected to encourage more efforts to
      maintain or improve the health status of the Medicare managed care population.

PMID- 11330451
TI  - Skin cancer prevention.

PMID- 11330452
TI  - Epidemiology of ovarian cancer: a summary review.
AB  - Ovarian cancer is among the five leading sites for cancer incidence and mortality
      in women from developed countries. Its incidence and mortality rates have,
      however, been declining over the last few decades following the introduction of
      oral contraceptives, which - together with parity - are the best recognized
      protective factor for the disease. Late menopause and irregular menstrual cycles
      may also reduce the risk, while the role of hormone replacement therapy in
      menopause and fertility treatments is still unclear. Cosmetic talc use and some
      aspect of diet (i.e. saturated fats, refined carbohydrates) have been associated
      with increased risk, in some--though not all--studies), while vegetable
      consumption appears to be inversely related to risk. These issues remain open to
      debate. Women with a family history of ovarian and breast cancer in first-degree
      relatives are also at increased risk, but family history accounts for only 4-5%
      of cases. Most ovarian cancers are therefore environmental in origin and
      consequently, at least in principle, avoidable.

PMID- 11330453
TI  - Do undesirable effects of screening affect all-cause mortality in flexible
      sigmoidoscopy programmes? Experience from the Telemark Polyp Study 1983-1996.
AB  - There is substantial evidence for the beneficial effect of screening programmes
      aimed at reducing mortality from colorectal cancer (CRC). The effect on all-cause
      mortality, however, may not necessarily be beneficial. In the present study we
      used the follow-up results 13 years after a flexible sigmoidoscopy screening to
      evaluate the long-term effects of informing participants about findings at
      flexible sigmoidoscopy (FS) screening. There were no severe complications and
      there was no long-term difference in deaths related to whether there had been any
      mucosal rupture (biopsy or snare resection) or not. As a group, those who
      attended in 1983 and were informed that they had polyps tended to improve their
      smoking habits more than those informed that they had no polyps. Similarly, and
      in spite of more people giving up smoking, the group with polyps had a trend
      towards a smaller increase in BMI (+0.7 (95% CI 0.2-1.1)) than the polyp-free
      group (+1.2 (95% CI 0.9-1.6)) (P = 0.07). The observations suggest that flexible
      sigmoidoscopy screening may face an educational challenge to avoid unfavourable
      changes in the lifestyle of screenees, an effect that may more than outweigh the
      beneficial effect of screening.

PMID- 11330454
TI  - Colonic cell proliferation, apoptosis and aberrant crypt foci development in rats
      given 2-amino-3-methylimidaz.
AB  - Sodium-copper chlorophyllin (CHL) inhibits the formation of 2-amino-3
      methylimidazo[4,5-f]quinoline (IQ)- and 2-amino-1-methyl-6-phenylimidazo[4,5
      b]pyridine (PhIP)-induced colonic aberrant crypt foci (ACF) and tumours in the
      F344 rat when it is given simultaneously with either carcinogen. However, CHL
      reportedly increased the incidence of dimethylhydrazine (DMH)-induced colon
      tumours in the same species when administered post-initiation. In the present
      study, rats were given IQ (130 mg/kg body weight, by oral gavages on alternating
      days) for 2 weeks, starting in experiment week 3, and one week after the final IQ
      dose rats received CHL treatment until the study was terminated at 16 weeks.
      Compared with animals given carcinogen alone, the mean number of IQ-induced ACF
      per colon was reduced significantly by 1% (w/v) CHL in the drinking water (P <
      0.05), whereas 0.1% and 0.01% CHL had no effect. These CHL concentrations
      increased in a dose-related manner both the terminal deoxynucleotidyl transferase
      mediated nick end labelling (TUNEL) and bromodeoxyuridine (BrdU) labelling
      indices in the distal colon. However, the lowest concentration tested, 0.001%
      CHL, increased the mean number of IQ-induced ACF per colon (P < 0.05), and
      increased the BrdU labelling index without a concomitant change in TUNEL. These
      studies indicated that 0.001% CHL promoted IQ-ACF due to deregulation of the
      homeostatic balance between cell birth and apoptosis in the colonic mucosa,
      whereas higher concentrations of CHL had either no effect or protected against IQ
      induced ACF by causing dose-related increases in the overall rate of cell
      turnover in the colon.

PMID- 11330455
TI  - Medical diagnostic X-ray radiation--an evaluation from medical records and
      dentist cards in a case-control study of thyroid cancer in the northern medical
      region of Sweden.
AB  - The aim of this study was to evaluate the association between thyroid cancer and
      diagnostic X-ray radiation based on medical records. By using the Swedish Cancer
      Registry, 187 living cases with thyroid cancer (81%), aged 20-70 years at the
      time of their diagnosis in 1980-1989 were identified in the Northern Health Care
      Region of Sweden. Seven cases were reclassified as having a disease other than
      thyroid cancer and were excluded. The investigation included 180 living cases and
      360 controls from the National Population Registry. In 132 cases and 251 controls
      data from X-ray records on earlier investigations > 5 years prior to diagnosis
      and corresponding years for the controls were analysed. The mean calculated
      thyroid dose for the cases was 7.0 mGy (median 1.1) and for the controls 7.4 mGy
      (median 1.0). This study showed no difference in the total material between
      calculated absorbed thyroid dose of medical diagnostic X-ray in cases versus
      controls. In younger women (< or = 50 years at diagnosis) with papillary thyroid
      cancer an association was found, however it was not significant. The results
      could be related to selective bias and should be treated with caution. Future
      studies require analysis of diagnostic medical X-ray investigations involving the
      thyroid gland including more specific data on sex and age of exposure in the
      whole study group.

PMID- 11330456
TI  - Organochlorine pesticides in carcinoma of the gallbladder: a case-control study.
AB  - Carcinoma of the gallbladder is the third most common malignancy of the
      gastrointestinal tract in the Eastern Uttar Pradesh and Western Bihar regions of
      India. The main source of drinking water in this region is the river Ganges,
      which is heavily polluted with agricultural pesticides. Organochlorine pesticides
      were estimated in bile by gas liquid chromatography in 60 patients (30 carcinoma
      of the gallbladder and 30 cholelithiasis) to observe its association with
      aetiopathogenesis of carcinoma of the gallbladder. The mean biliary concentration
      of benzene hexachloride (BHC) was found to be significantly higher in carcinoma
      of the gallbladder (0.0471 ppm) than in cholelithiasis (0.0352 ppm) (P < 0.04).
      The mean biliary concentration of dichlorodiphenyltrichloroethane (DDT) was also
      significantly higher in carcinoma of the gallbladder (0.418 ppm) than in
      cholelithiasis (0.0103 ppm) (P < 0.03). Biliary aldrin and endosulfan
      concentrations were higher in carcinoma of the gallbladder (0.0008 and 0.00132
      ppm) than in cholelithiasis (0.0005 and 0.0126 ppm) but the difference was
      statistically not significant (P < 0.06 and P < 0.9). The levels of pesticides in
      blood did not show significant differences in either carcinoma of the gallbladder
      or cholelithiasis. Significantly high biliary BHC and DDT concentrations suggest
      that these pesticides might be associated with gallbladder carcinogenesi.

PMID- 11330457
TI  - The European Society of Skin Cancer Prevention--EUROSKIN: towards the promotion
      and harmonization of skin cancer prevention in Europe. Recommendations.

PMID- 11330458
TI  - Inflammation promotes Barrett's metaplasia and cancer: a unique role for
      TNFalpha.

PMID- 11330459
TI  - Faecal occult blood testing in the secondary prevention of colorectal cancer.

PMID- 11330460
TI  - Endoscopic screening in the prevention of colorectal cancer.

PMID- 11330461
TI  - Variation in survival of patients with digestive tract cancers in Europe, 1978
      1989.

PMID- 11330462
TI  - Screening colonoscopy in asymptomatic increased-risk subjects.

PMID- 11330463
TI  - Diet and human cancer: a review.

PMID- 11330464
TI  - ECP dietary advice on cancer prevention.

PMID- 11330465
TI  - Diet and risk of oral and pharyngeal cancer. An Italian case-control study.
AB  - The relation between diet and risk of oral and pharyngeal cancer was analysed in
      a case-control study conducted in North-East Italy between 1996 and 1999. Cases
      were 132 patients (including 33 women), with incident, histologically confirmed
      cancer of the oral cavity or pharynx, and controls were 148 subjects (including
      45 women) admitted to hospitals for acute conditions unrelated to smoking or
      alcohol drinking. After allowance for tobacco, alcohol and several other
      potential confounding factors, significant inverse association with the risk of
      oral and pharyngeal cancer was found for consumption of total green vegetables
      (OR 0.37) and total fruit (OR 0.34) with significant trends in risk Compared with
      alcohol drinkers of < 20 drinks/week and eating > 13 portions/week of total green
      vegetables, the OR for drinkers of > or = 20 drinks/week and eating < 7
      portions/week of green vegetables was 15.44. Our study provides further support
      to the beneficial effect of high intake of vegetables and fruit, particularly in
      heavy smokers and alcohol drinkers.

PMID- 11330466
TI  - Origin of ovarian cancer from benign cysts.
AB  - In a case-control study of 1031 epithelial ovarian cancers and 2311 controls
      conducted in Italy, 56 cases and 116 controls reported history of benign ovarian
      cysts, corresponding to a relative risk of 1.3 (95% confidence interval = 0.9
      1.8). In a subset of 255 histologically reviewed cases, mucinous and endometrioid
      ovarian neoplasms and neoplasms of stage I or II arose more frequently from
      cysts, while use of oral contraceptives or parity were not significantly related
      to history of ovarian cysts.

PMID- 11330467
TI  - The kinetics and mechanisms of the reactions of aluminium(III) with gallic acid,
      gallic acid methyl ester and adrenaline.
AB  - The kinetics and mechanisms of the reactions of gallic acid, gallic acid methyl
      ester and adrenaline with aluminium(III) have been investigated in aqueous
      solution at 25 degrees C and an ionic strength of 0.5 M. A mechanism has been
      proposed which accounts satisfactorily for the kinetic data. This is consistent
      with a mechanism in which complex formation takes place almost exclusively by
      reaction of [Al(H2O)5OH]2+ with the ligands. [Al(H2O)5OH]2+ reacts with gallic
      acid, gallic acid methyl ester and adrenaline with rate constants of 1145, 1330
      and 316 M(-1) s(-1) respectively. These data together with the equilibrium data
      enable the rate constants for reaction of [Al(H2O)6]3+ with both gallic acid and
      gallic acid methyl ester to be calculated. In view of the dissociative nature of
      water exchange on [Al(H2O)6]3+ and [Al(H2O)5(OH)]2+ the complex formation rate
      constants are discussed in terms of the Eigen-Wilkins-Tamm mechanism. The overall
      mechanisms have been validated using global analysis. The results are compared
      with previously published data on the complex formation reactions of
      aluminium(III). In addition, the rate constants and mechanisms for replacement of
      maltol by gallic acid methyl ester and diethylenetriaminepentaacetic acid (dtpa)
      have been investigated.

PMID- 11330468
TI  - Investigation of the ternary D-myo-inositol 1,2,6-tris(phosphate)-spermine-Zn2+
      system in solution.
AB  - Interactions of Ins(1,2,6)P3 (IP), with spermine (Spm) and zinc cations have been
      studied by potentiometric and 31P NMR titrations. In the 4-11 pH range, two
      IPSpmZn2H3 and IPSpmZn2H mixed complexes are formed which are largely predominant
      with respect to the binary species. According to 31P NMR titration it is likely
      that one of the zinc cations preferably binds phosphates P1 and P6. The adduct
      formation between Ins(1,2,6)P3 and spermine seems also favourable to the
      formation of the mixed complexes. The occurrence of ternary complexes involving
      inositol-phosphates, biogenic amines, and metallic cations may be of relevance in
      the regulation of biological processes.

PMID- 11330469
TI  - Ester hydrolysis with 2,6-di(pyrazol-3-yl)pyridines and their CoII complexes in
      homogeneous and micellar media.
AB  - The 1:1 complex of Co(ClO4)2 with the H2O-insoluble tridentate 2,6-di(1H-4,5,6,7
      tetrahydroindazol-3-yl)pyridine (H21) was found to be an excellent catalyst for
      the hydrolysis of para-nitrophenyl acetate in aqueous buffers over the pH 7.05
      7.90 range, with an estimated second-order rate constant of 0.50 M(-1) s(-1). The
      Co2+ complexes of the N,N'-di-1-dodecyl analogue in micellar media and the N,N'
      di-(4-carboxyphenyl) analogue in aqueous media were much poorer catalysts, poorer
      than the free ligands. In all cases, the pH-rate profiles indicated that free
      base, deprotonated or hydroxo forms were the active species. The greater success
      with Co(H(2)1)2+ indicated a catalytic role for N-H deprotonation.

PMID- 11330470
TI  - The binding of [(en)Pt(mu-dpzm)2Pt(en)]4+ to G/C-rich regions of DNA.
AB  - The non-covalent binding of [(en)Pt(mu-dpzm)2Pt(en)]4+ to segments of DNA
      containing only G and C bases has been studied to gain an understanding of the
      pre-covalent binding association of cationic polynuclear platinum(II) anti-cancer
      drugs at G/C sites. 1H-NMR and CD spectroscopy were used to study the binding of
      the metal complex to the oligonucleotide d(GC)5 and the polynucleotide poly(dG
      dC).poly(dG-dC), respectively. NOE contacts between the metal complex protons and
      the oligonucleotide sugar H1' protons observed in NOESY spectra indicated that
      the metal complex bound in the minor groove at the central C4 to G7 region of the
      oligonucleotide. This result indicates that even though cationic polynuclear
      platinum(II) complexes bind covalently in the major groove at G/C sites, the pre
      covalent binding association is favoured in the minor groove. CD spectra
      indicated that the addition of the metal complex to poly(dG-dC)-poly(dG-dC)
      induced some conformational changes, but it was not possible to conclude that
      [(en)Pt(mu-dpzm)2Pt(en)]4+ induced a B- to Z-type DNA transition. In addition, in
      vitro transcription assays using the lac UV5 promoter showed that the non
      covalent binding of [(en)Pt(mu-dpzm)2Pt(en)]4+ was sufficiently stable to inhibit
      transcription, and at particular sites.

PMID- 11330471
TI  - Comparison of the reactivity of oxaliplatin, pt(diaminocyclohexane)Cl2 and
      pt(diaminocyclohexane1)(OH2)2(2+) with guanosine and L-methionine.
AB  - The initial rates of reactivity of oxaliplatin, its metabolites Pt(dach)Cl2 and
      Pt(dach)(OH2)2(2+) with guanosine and L-met in water, NaCl and phosphate were
      compared. Versus guanosine, the most reactive molecule was Pt(dach)(OH2)2(2+),
      about 40 fold that of oxaliplatin, the least reactive was Pt(dach)Cl2, Versus L
      met, Pt(dach)(OH2)2(2+), was also the most reactive species but only about 2 fold
      more reactive than Pt(dach)Cl2 and oxaliplatin. Pt(dach)(OH2)2(2+) was
      approximately 3 fold less reactive versus methionine than guanosine whereas
      oxaliplatin and Pt(dach)Cl2 were about seven fold more reactive versus methionine
      than guanosine. Thus, the three platinum compounds oxaliplatin, Pt(dach)Cl2 and
      Pt(dach)(OH2)2(2+) react with L-met but only the Pt(dach)(OH2)2(2+) has a high
      reactivity with guanosine. Oxaliplatin, which is stable in water, has to be
      transformed in the presence of chloride in chloro-derivatives which are aquated
      to become active particularly versus guanosine. These data demonstrate that
      oxaliplatin has similarities with cisplatin in terms of chloride versus water
      coordination and in terms of dependence on chloride concentration for
      transformations.

PMID- 11330472
TI  - Complexes of aluminium(III) with glucose-6-phosphate in aqueous solutions.
AB  - The interaction of aluminium(III) with glucose-6-phosphate (GP: LH2) in aqueous
      solutions has been studied from pH 1 to pH 8, by pH-potentiometry and
      multinuclear (31P, 27Al, 13C) NMR spectroscopy. Various mononuclear species
      (MLH2, MLH, ML, ML2H, ML2 and MLH(-3)) and dinuclear complexes M2L2H-n (n=1-4)
      are formed in the system. NMR clearly indicates that GP is already bound to
      Al(III) at pH 1. The potentiometric speciation results are confirmed and
      completed by spectroscopic experiments. Many peaks are observed in the 31P NMR
      spectra suggesting the formation of isomeric species. An attempt to assign the
      signals to the corresponding complexes is made, allowing a discussion about their
      structure. Interestingly enough no metal ion-induced deprotonation and
      coordination of the alcoholic-OH functions have been observed.

PMID- 11330473
TI  - Formation of mu-oxo dimer by the reaction of (meso
      tetraphenylporphyrinato)iron(III) with various imidazoles.
AB  - Reactions between (meso-tetraphenylporphyrinato)iron(III) perchlorate
      [Fe(tpp)]ClO4 and various imidazoles have been examined in CD2Cl2 solutions. 1H
      NMR analysis revealed the formation of three kinds of complex; mu-oxo dimer, mono
      imidazole adduct, and bis-imidazole adduct. The product ratios changed to a great
      extent depending on the amount and nature of imidazoles. In general, addition of
      less than 1.0 equiv of imidazole relative to [Fe(tpp)]ClO4 led to the formation
      of both mu-oxo dimer and mono-imidazole adduct. However, by the addition of
      excess amount of imidazole, either the mu-oxo dimer or bis-imidazole adduct was
      formed exclusively depending on the bulkiness of the imidazole used. In the case
      of bulky imidazole such as 2-methylbenzimidazole or 2-isopropyl-1
      methylimidazole, the mu-oxo dimer was formed quantitatively. In the case of less
      bulky imidazole such as parent imidazole or 1-methylimidazole, bis-imidazole
      adduct became the sole product. The results have been explained in terms of the
      difference in steric interactions between the axial ligands and porphyrin core;
      the severe steric repulsion prohibits the formation of bis-adduct in the case of
      bulky imidazoles. As a result, bulky imidazoles prefer to behave as a base; they
      abstract a proton from coordinated water, and lead to the formation of mu-oxo
      dimer. Thus, the role of bulky imidazoles in these reactions has some relevance
      to that of distal histidine in hemoglobin and peroxidase.

PMID- 11330474
TI  - Tautomeric energetics of xanthine oxidase substrates: xanthine, 2-oxo-6
      methylpurine, and lumazine.
AB  - The stability of the tautomers of each of the three important substrates of
      xanthine oxidase, xanthine, 2-oxo-6-methylpurine, and lumazine, was examined by
      quantum mechanical calculations. The geometries of these tautomers were optimized
      at the AM1, Hartree-Fock (HF/6-31G), and hybrid Hartree-Fock/density functional
      theory (B3LYP/6-31G(d)) levels of theory. The single point energies of some of
      the more stable tautomers for each of the substrates were calculated at the
      B3LYP/6-311 +G(2d,p) level of theory. The Conductor Polarized Continuum Model
      (CPCM) was used to evaluate the solvent effects on the relative stabilities of
      these tautomers. The calculations clearly identify the lowest energy tautomeric
      form for xanthine and lumazine. On the other hand, there appear to be three
      tautomers for 2-oxo-6-methylpurine, with only minor energetic differences in
      vacuo. In water, however, only one of them predominates. The lowest energy
      tautomers presumably represent the predominant tautomeric forms at the molybdenum
      center of xanthine oxidase during catalysis. Implications of these computational
      results are discussed in the context of enzyme catalysis.

PMID- 11330475
TI  - Selenoprotein W in overexpressed and underexpressed rat glial cells in culture.
AB  - Selenium deficiency results in undetectable levels of selenoprotein W (SeW) in
      muscle but has very little effect upon its content in the brain and thus rat
      glial cells were studied. Previous work showed that glutathione (GSH) is bound to
      SeW and this study was undertaken to elucidate its possible antioxidant
      functions. Full length cDNA of SeW was cloned to inducible LacSwitch expression
      vector and stably transfected in C6 rat glial cells. After induction, SeW and its
      mRNA were expressed 22- and 11-fold higher respectively than control. The cDNA
      coding region of SeW was cloned to the vector in the antisense direction and
      stably transfected in C6 cells for underexpression of the protein. After
      induction, SeW expression was reduced to 20% of the control cells. Glutathione
      peroxidase activity and GSH levels were not significantly different between
      induced and control cells. There was a greater survival rate of overexpressed
      than control cells when incubated with 2,2'-Azobis (2-amidinopropane)
      dihydrochloride (AAPH), suggesting SeW possibly has an antioxidant function.

PMID- 11330476
TI  - Platinum (II) complex with cyclometalating 2-phenylpyridine ligand showing high
      cytotoxicity against cisplatin-resistant cell.
AB  - A platinum (II) mononuclear complex with two kinds of 2-phenylpyridine which
      coordinate as cyclometalated and non-chelated ligands shows high cytotoxicity
      against cisplatin-resistant mouse sarcoma 180 cell in comparison with its related
      complexes.

PMID- 11330477
TI  - Enhanced anti-cancer activities of some derivatives of titanocene dichloride.
AB  - The compounds (eta5-C5H5)2TiCl2 (I), currently undergoing phase II trials, (eta5
      C5H5)(eta5-C5H4CO2Me)TiCl2 (II) and C5H4CO2Me)2TiCl2 (III) are assessed for their
      efficacies against a small lung cancer cell line. It is found that the
      introduction of the electron withdrawing carbomethoxy group into the
      cyclopentadienyl rings increases the effectiveness of this class of drugs, such
      that III compares favorably with the well known cisplatin.

PMID- 11330478
TI  - Preparation, physicochemical properties and biological activity of copper(II)
      complexes with 6-(2-chlorobenzylamino)purine (HL1) or 6-(3
      chlorobenzylamino)purine (HL2). The single-crystal X-ray structure of.
AB  - Copper(II) complexes of 6-(2-chlorobenzylamino)purine (HL1) and 6-(3
      chlorobenzylamino)purine (HL2), respectively, were prepared. Depending on the pH
      of the medium and the molar ratio of reactants the following mononuclear
      (trigonal-bipyramidal) and dinuclear (octahedral, trigonal-bipyramidal or
      tetrahedral) complexes were isolated: [Cu2(mu-HL1)2(mu-Cl2)2(HL1)2Cl2] (1a,b),
      [Cu2(mu-Cl)2(mu-L1)2(H2O)2] (2a), [Cu2(mu-Cl)2(mu-L2)2(H2O)2] (2b),
      [Cu(H+L2)2Cl3]Cl.H2O (3a,b), [Cu2(mu-Cl)2(HL1)2Cl2] (4a), and [Cu2(mu
      Cl)2(HL2)2Cl2] (4b). The compounds were characterized by elemental analyses,
      electronic, infrared and mass (FAB+, ES+) spectral data, magnetic susceptibility
      temperature dependence measurements and molar conductivity data. An X-ray single
      crystal structural analysis of [Cu(H+L2)2Cl3]Cl.2H2O (3b) showed that the Cu2+
      ion is penta-coordinated by three chloride ions and by two H+L2 ligands. Thus,
      the Cu2+ ion adopts a distorted trigonal bipyramidal coordination geometry with
      the protonated H+L2 ligands coordinated in trans apical positions, while the
      three chloride ions are situated in an equatorial plane. The cytotoxic activity
      of the complexes was determined by a calcein AM assay. Mouse melanoma cell line
      B16-FO, human malignant melanoma cell line G361, human osteogenic sarcoma cell
      line HOS and human breast adenocarcinoma cell line MCF7 were used. IC50 values,
      the drug concentrations lethal to 50% of the tumor cells, were estimated. One of
      the important mechanisms responsible for the cytotoxicity of cytokinin-derived
      compounds, the inhibition of cyclin-dependent kinases by the studied complexes,
      was also determined.

PMID- 11330479
TI  - Synthesis and characterization of a binuclear coumarin-3-carboxylate copper(II)
      complex.
AB  - The copper(II) complex of coumarin-3-carboxylic acid (CcaH) has been prepared and
      characterized on the basis of elemental and thermal analysis, IR, Raman, EPR, UV
      Vis reflectance and 1H-NMR spectra. A detail analysis of all spectra data is
      presented with particular emphasis on the elucidation of the coordination mode of
      the ligand and the structure of the complex. All data are consistent with a
      binuclear structure for the complex with four coumarin-3-carboxylates as bridges
      and one water ligand per copper ion. The significantly lower than the spin-only
      value magnetic moment of the complex and the EPR spectra at various temperature
      are indicative of a magnetic interaction between the two copper atoms.

PMID- 11330480
TI  - Intramolecular stacking interactions in ternary copper(II) complexes formed with
      2,2'-bipyridine or 1,10-phenanthroline and 9-(4-phosphonobutyl)adenine (dPMEA),
      the carba relative of the antiviral nucleotide analogue 9.
AB  - The stability constants of the mixed ligand complexes formed between Cu(Arm)2+,
      where Arm=2,2'-bipyridine (Bpy) or 1,10-phenanthroline (Phen), and the monoanion
      or the dianion of 9-(4-phosphonobutyl)adenine (dPMEA=3'-deoxa-PMEA), which is the
      carba analogue of the antivirally active 9-[2-(phosphonomethoxy)ethyl]adenine
      (PMEA), were determined by potentiometric pH titrations in aqueous solution at 25
      degrees C and I=0.1 M (NaNO3). Detailed stability constant comparisons reveal
      that in the monoprotonated ternary Cu(Arm)(H;dPMEA)+ complexes the proton is at
      the phosphonate group and that stacking between Cu(Arm)2+ and H(dPMEA)- plays a
      significant role. For the Cu(Arm)(dPMEA) complexes a large increase in complex
      stability (compared to the stability expected on the basis of the basicity of the
      phosphonate group) is observed, which is due to intramolecular stack formation
      between the aromatic ring systems of Phen or Bpy and the purine moiety of dPMEA2
      . The formation degree of the stacked isomer in the Cu(Arm)(dPMEA) systems is on
      the order of 90%, though it is somewhat more pronounced with Phen than with Bpy.
      Comparisons of the Cu(Arm)(N) systems, where N=dPMEA2- and PMEA2- or adenosine 5'
      monophosphate (AMP2-), reveal that the stacking properties of dPMEA2- and PMEA2
      resemble closely those of their parent nucleotide AMP2-.

PMID- 11330481
TI  - Ni(II) and Cu(II) binding with a 14-aminoacid sequence of Cap43 protein,
      TRSRSHTSEGTRSR.
AB  - The tetradecapeptide containing the 10 aminoacid repeated sequence on the C
      terminus of the Ni(II)-induced Cap43 protein, was analyzed for Ni(II) and Cu(II)
      binding. A combined pH-metric and spectroscopic UV-VIS, EPR, CD and NMR study of
      Ni(II) and Cu(II) binding to the blocked CH3CO-Thr-Arg-Ser-Arg-Ser-His-Thr-Ser
      Glu-Gly-Thr-Arg-Ser-Arg-NH2 (Ac-TRSRSHTSEGTRSR-Am) peptide, modeling a part of
      the C-terminal sequence of the Cap43 protein, revealed the formation of
      octahedral complexes involving imidazole nitrogen of histidine, at pH 5.5 and pH
      7 for Cu(II) and Ni(II), respectively; a major square planar 4N-Ni(II) complex
      (about 100% at pH 9, log K* = -28.16) involving imidazole nitrogen of histidine
      and three deprotonated amide nitrogens of the backbone of the peptide was
      revealed; a 3N-Cu(II) complex (maximum about 70% at pH 7, log K*=-13.91) and a
      series of 4N-Cu(II) complexes starting at pH 5.5 (maximum about 90% at pH 8.7,
      log K* = -21.39 for CuH(-3)L), were revealed. This work supports the existence of
      a metal binding site at the COOH-terminal part of the Cap43 peptide.

PMID- 11330482
TI  - Synthesis, structural characterization and antimicrobial activities of 4- and 6
      coordinate nickel(II) complexes with three thiosemicarbazones and semicarbazone
      ligands.
AB  - To investigate the relationship between antimicrobial activities and the
      molecular structures of nickel(II) complexes with thiosemicarbazone and
      semicarbazone ligands, nickel(II) complexes with ligands Hmtsc, Hatsc, Hasc and
      H2dmtsc, were prepared and characterized by elemental analysis, FT-IR, 1H and 13C
      NMR spectroscopies, magnetic susceptibility measurements, UV-Vis absorption
      spectra, TG/DTA and single-crystal X-ray analysis. Their antimicrobial activities
      were evaluated by the MIC against four bacteria (B. subtilis, S. aureus, E. coli
      and P. aeruginosa), two yeasts (C. albicans and S. cerevisiae) and two molds (A.
      niger and P. citrinum). The 4-coordinate, diamagnetic nickel(II) complexes showed
      antimicrobial activities which were different from those of free ligands or the
      starting nickel(II) compounds; [Ni(mtsc)(OAc)] 1 showed selective and effective
      antimicrobial activities against two Gram-positive bacteria (B. subtilis and S.
      aureus) and modest activities against a yeast (S. cerevisiae), [Ni(mtsc)Cl] 3
      exhibited moderate activities against a Gram-positive bacterium (S. aureus), and
      [Ni(atsc)(OAc)] 5 showed modest activities against two Gram-positive bacteria (B.
      subtilis and S. aureus). On the other hand, the 6-coordinate, paramagnetic
      nickel(II) complexes with two protonated or deprotonated ligands ([Ni(mtsc)2] 2,
      [Ni(atsc)(mtsc)] 4, [Ni(atsc)2] 6, [Ni(Hatsc)2](NO3)(2)7, [Ni(Hatsc)2]Cl(2)8 and
      [Ni(Hasc)2](OAc)(2)9) and the sterically crowded 4-coordinate, diamagnetic
      nickel(II) complex ([Ni(dmtsc)] 10) did not inhibit the growth of the test
      organisms. The structure-activity correlation in this series of nickel(II)
      complexes was discussed based on their ligand-replacement abilities.

PMID- 11330483
TI  - Nature of cerium(III)- and lanthanum(III)-induced aggregation of human
      erythrocyte membrane proteins.
AB  - To clarify the nature of the aggregation of membrane proteins (MP) induced by
      lanthanide cations (Lns), the interaction of cerium(III) (Ce3+) and
      lanthanum(III)(La3+) with erythrocyte membrane proteins was studied by means of
      SDS-PAGE, light scattering measurement, fluorescence, CD and FTIR spectra. The
      results showed that Ce3+ and La3+ induce protein aggregation not only by Lns non
      covalent binding and cross-linking, but also by oxidative cross-linking through
      disulfide bond formation. As demonstrated by intrinsic fluorescence, CD and FTIR
      spectra studies, the aggregation was accompanied by the conformation changes with
      tryptophane residues exposing to more hydrophobic environment and the decreasing
      alpha-helix and beta-sheet contents. By stopped-flow studies, protein aggregation
      was shown to be a slow change, which is initiated by rapid Lns binding and then
      followed by subsequent conformational changes.

PMID- 11330484
TI  - Coordination of heavy metals by dithiothreitol, a commonly used thiol group
      protectant.
AB  - D,L-Dithiothreitol (DTT), known also as Cleland reagent, is a thiol group
      protectant, used commonly in peptide and protein chemistry. Therefore, it is
      often added at high concentrations in preparations of proteins relevant to heavy
      metal biochemistry. The coordination of five of these metal ions, Zn(II), Cd(II),
      Pb(II), Ni(II) and Cu(I) to DTT was studied by means of potentiometric
      titrations, and UV-Vis and NMR spectroscopies. It was found that DTT forms
      specific and very stable polymeric and monomeric complexes with all of these
      metal ions, using both of its sulfur donors. The quantitative description of
      these complexes in solution and the solid state provides the basis for
      predictions of interference from DTT in studies of metal ion binding of thiol
      containing biomolecules.

PMID- 11330485
TI  - Interruption of the MnO2 oxidative process on dopamine and L-dopa by the action
      of S2O3(2-).
AB  - The oxidation effects of Mn2+, Mn3+ or MnO2 on dopamine can be studied in vitro
      and, therefore, this offers a model of the auto-oxidation process that appears
      naturally in neurons causing Parkinson's disease. The use of MnO, as an oxidizer
      in aqueous solution at pH 7 causes the oxidation of catecholamines (L-dopa,
      dopamine, noradrenaline and adrenaline) to melanin. However, this work shows
      that, in water at pH 6-7, the oxidation of catecholamines by MnO2 in the presence
      of sodium thiosulphate (Na2S2O3) occurs by other mechanisms. For dopamine and L
      dopa, MLCT complexes were formed with bands at 312, 350 (sh), 554 (sh) nm, and an
      intense band at 597 nm (epsilon approximately/= 4 x 10(3) M(-1) cm(-1)) and at
      ca. 336, 557 (sh) nm, and an intense band at 597 nm (epsilon approximately 6 x
      10(3) M(-1) cm(-1)), respectively. The latter transitions were assigned to d(pi)-
      >pi*-SQ. Noradrenaline and adrenaline do not form this blue complex in solution,
      but generate soluble oxidized compounds. The resonance Raman spectra of these
      complexes in solution showed bands at 950, 1006, 1258, 1378, 1508 and 1603 cm(-1)
      for the complex derivation of L-dopa and at 948, 1010, 1255, 1373, 1510 and 1603
      cm(-1) for the dopamine-derived compound. The most intense Raman band at ca. 1378
      cm(-1) was assigned to C-O stretching with major C1-C2 characteristics and
      indicated that dopamine and L-dopa do not occur complexed with manganese in the
      catecholate or quinone form, but suggests an intermediate compound such as an
      anionic o-semiquinone (SQ-), forming a complex such as [Mn(II)(SQ-)3]-. All
      enhanced Raman frequencies are characteristic of the benzenic ring without the
      participation of the aminic nitrogen. A mechanism is proposed for the formation
      of the dopamine and L-dopa complexes and a computational simulation was performed
      to support it.

PMID- 11330486
TI  - Possible role of hydroxyl radicals in the oxidation of dichloroacetonitrile by
      Fenton-like reaction.
AB  - Dichloroacetonitrile (DCAN), is a member of haloacetonitrile group and detected
      in drinking water supplies as a by-product of chlorination process. The mechanism
      of DCAN-induced carcinogenesis is believed to be mediated by oxidative
      bioactivation of DCAN molecules. The present study was designed to investigate if
      reactive oxygen species (ROS), similar to that generated in biological systems,
      are capable of oxidative activation of DCAN. A model ROS generation system
      (Fenton-like reaction; Fe2+ and H2O2) that predominantly produces hydroxyl
      radical (OH*) was used. DCAN oxidation was monitored by the extent of cyanide (CN
      ) release. The results indicate that DCAN was markedly oxidized by this system,
      and the rate of oxidation was dependent on DCAN concentration. Four-fold increase
      in H2O2 concentration (50-200 mM) resulted in a 35-fold increase in CN- release.
      The rates of DACN oxidation in presence of various transition metals were in the
      following order; iron>copper>titanium. DCAN oxidation was enhanced significantly
      by the addition of vitamin C and sulfhydryl compounds such as glutathione, N
      acetyl-L- cysteine, and dithiothreitol (10 mM) to 140, 130, 145 and 136% of
      control, respectively. Addition of H2O2 scavenger; catalase or iron chelator;
      desferrioxamine (DFO) resulted in a significant decrease in CN- release 47 and
      41% of control, respectively. Addition of various concentrations of the free
      radical scavengers, DMSO, or mannitol, to the incubation mixtures caused a
      significant decrease in DCAN oxidation, 32 and 50% of control, respectively.
      Michaelis-Menten kinetic analysis of the rates of this reaction, with or without
      inhibitors, indicated that ROS mediated oxidation of DCAN was inhibited by
      catalase (Ki = 0.01 mM)>DFO (0.02 mM) > mannitol (0.09 mM) > DMSO (0.12 mM). In
      conclusion, our results indicate that DCAN is oxidized by a ROS-mediated
      mechanism. This mechanism may have an important role in DCAN bioactivation and
      DCAN-induced genotoxicity at target organs where multiple forms of ROS generating
      systems are abundant.

PMID- 11330487
TI  - Prediction and control as determinants of behavioural uncertainty: effects on
      task performance and heart rate reactivity.
AB  - Control or control-belief is often viewed as being directly instrumental in
      facilitating coping mechanisms in aversive situations, and yet the empirical
      evidence for the beneficial effects of control is inconclusive. In this study we
      investigated the role of predictability in determining the effects of perceived
      control during an aversive reaction time task. Fifty-six subjects were allocated
      to one of four groups; predictable-control, predictable-no control, unpredictable
      control, unpredictable-no control. In the predictable conditions, subjects could
      temporally predict the occurrence of an aversive noise. In the perceived control
      conditions, duration of the aversive tone was contingent on subject's
      performance. All subjects were matched in terms of the nature of the task and in
      the number and time of receipt of both the warning signal and noise. Heart rate
      reactivity and two performance parameters were measured, reaction time and
      performance increase. Both predictability and control-belief led to a reduction
      in heart rate reactivity, although they appeared to function independently and at
      different points in the sequence of events. That is, predictability or perceived
      control was sufficient to mitigate the effects of an aversive situation. Neither
      perception of control or predictability led to better task performance. These
      results are discussed in terms of behavioural uncertainty explanations.

PMID- 11330488
TI  - Explanatory style and Immunoglobulin A (IgA).
AB  - The construct of explanatory style has been related to numerous aspects of human
      psychology, including health. Our research has focused on the effects of various
      psychological variables on the immune system, in particular Immunoglobulin A
      (IgA). We had participants fill out the Attributional Style Questionnaire (ASQ),
      the predominant measure of explanatory style, and assayed saliva samples for
      secretory IgA. No relationship was observed between overall ASQ score and IgA, or
      composite optimism score and IgA. However, we observed significant negative
      correlations between both the composite pessimism score and IgA, as well as the
      hopelessness score and IgA. Pessimistic explanatory style may therefore be
      related to immune system deficits and poor health.

PMID- 11330489
TI  - Motilin- and neuropeptide Y-like immunoreactivity in a psychophysiological stress
      experiment on patients with functional dyspepsia.
AB  - BACKGROUND: The aim of the study was to compare plasma motilin-like
      immunoreactivity (MOT-LI) and neuropeptide Y (NPY)-like immunoreactivity (NPY-LI)
      in patients with functional dyspepsia (FD) during a controlled
      psychophysiological experiment. METHOD: 25 patients (12 men, 13 women), age 24
      50, with recurrent FD, and 25 pair-wise sex- and age-matched community control
      subjects were studied. In an experiment, after a rest period, subjects were
      studied during a 15-min stress interview. The aim of the interview was to elicit
      anxiety. Before and during the intervention blood samples were drawn for peptide
      analyses. Outcome measures were the Gastrointestinal Symptom Rating Scale,
      fasting blood glucose, heart rate and blood pressure as well as the subjects'
      self-ratings on visual analogue scales. The plasma concentrations of MOT-LI and
      NPY-LI are given as anti-logarithms. RESULTS: Mean plasma MOT-LI concentration
      was 7.3 (CI: 5.7-9.4) pmol/L in the patient group, and 7.9 (CI: 6.1-10.2) pmol/L
      in the control group. Mean plasma NPY-LI concentration was 14.2 (CI: 12.3-16.4)
      pmol/L in the patient group, and 13.4 (Cl: 11.8-15.3) pmol/L in the control
      group. Using ANCOVA (covariates: group, gender, age, body mass index and smoking)
      MOT-LI was related to lower indigestion symptomatology (p<0.04) and positive
      change in joyfulness during the interview (p<0.03). In the patient group delta
      motilin correlated with increased joyfulness (p<0.03) and decreased sadness
      (p<0.03). The NPY-LI increase during the interview was related to higher fasting
      blood glucose before the interview (p<0.01) and a stronger increase in systolic
      blood pressure during the test (p<0.05). CONCLUSION: During a stress interview
      plasma MOT-LI is positively related to less indigestion symptomatology and
      joyfulness, while changes in plasma NPY-LI were positively related to sympathetic
      nervous system activity, but not to gastrointestinal symptoms.

PMID- 11330490
TI  - Ivan P. Pavlov's view on vivisection.
AB  - Pavlov's points of view on vivisection are analyzed and compared with the modern
      ethical conception of carrying out experiments on animals. It appears that
      Pavlov's points of view are largely in accordance with modern ethical
      requirements for experimenting on animals.

PMID- 11330491
TI  - The perception of available social support is related to reduced cardiovascular
      reactivity in Phase II cardiac rehabilitation patients.
AB  - OBJECTIVE: Numerous studies have observed a relationship between social support
      (SS) and post coronary event survival. Laboratory research suggests one mechanism
      regulating this relationship may be exaggerated cardiovascular reactivity (CVR).
      What has not been as well explored is (1) whether the SS-CVR relationship holds
      up for a heart diseased sample, and (2) whether this relationship is evidenced
      only in supportive environments or can be found as a function of generalized
      perception of being socially supported. Thus, the purpose of this study was to
      examine the relationship of perceived SS and a locally supportive presence to CVR
      to a speech-induced stressor in post coronary event patients. METHOD: Forty-one
      Phase II cardiac rehabilitation patients participated in a research protocol that
      consisted of BP and HR measurement during two identical affective stress
      interviews where local support was systematically varied by presence or absence
      of a friendly small pet dog. Perception of SS was assessed by completion of
      psychosocial questionnaire packet that included measures of SS, anger expression
      and pet attachment. RESULTS: Repeated measures ANCOVAs revealed that patients who
      believed they had greater SS available to them during difficult times exhibited
      significantly less CVR for MAP (p<.007) and DBP (p<.024). No significant main
      effects for local support (pet presence) and no interactions between local and
      perceived support were found. CONCLUSIONS: These findings are of interest as
      they: (a) demonstrate an association between reduced CVR and higher (amounts of)
      SS in a clinical sample; (b) demonstrate this effect in a sample medicated to
      dampen CV levels and surges; (c) suggest that perceived amount of SS provides an
      ameliorative influence on CVR independent of situational support; (d) suggest
      that for certain conditions pet-models of support may be ineffective at
      establishing an local support presence.

PMID- 11330492
TI  - An electrophysiological study of school-aged children with a history of failure
      to thrive during infancy.
AB  - Sixty-five subjects, ages 8 to 12, participated in a visual electrophysiological
      study. Twenty-two of the subjects had received a diagnosis of nonorganic failure
      to-thrive (FTT) before the age of three. The remaining 43 subjects had no history
      of FTT and served as Controls. IQs were obtained with the abbreviated WISC-III,
      and the Controls were split into two groups, LO IQ and HI IQ, to provide a LO IQ
      Control group with an average IQ equivalent to the FTT group. Event-related brain
      potentials (ERPs) were recorded from five scalp locations during a cued
      continuous performance task (CPT). Subjects had to press a button every time they
      saw the letter "X" following the letter "A" (50 targets out of 400 stimuli).
      During the CPT, the FTT subjects made marginally more errors of omission to
      targets than the LO IQ Control group and significantly more errors of omission
      than the HI IQ Control subjects. The groups did not differ significantly on
      errors of commission (false alarms) or reaction times to targets. ERP averages
      revealed a group difference in amplitude in a late slow wave for the 50 non-X
      stimuli (false targets) that followed the letter A. This difference was greatest
      over frontal sites, where the FTT group had a more negative going slow wave than
      each control group. Late frontal negativity to No Go stimuli has been linked with
      post-decisional processing, notably in young children. Thus, the FTT subjects may
      have less efficient inhibitory processes, reflected by additional late frontal
      activation.

PMID- 11330493
TI  - Does binge eating play a role in the self-regulation of moods?
AB  - Self-reported emotional experiences and eating behaviors were studied in college
      students in an attempt to determine what types of emotional experiences precede
      and follow binge eating and how specific types of compensatory behaviors modify
      these experiences. First-year male and female students (N=390) were surveyed for
      depression, anxiety, health status, life satisfaction, and eating attitudes (EAT
      26). Those reporting recurrent binge eating episodes were asked to describe their
      emotional feelings before and after bingeing and before and after compensatory
      activities. EAT-26 scores corresponding to scores previously reported for eating
      disordered patients were found in 9.7% of students. Binge eating was nearly twice
      as frequent among females (16.4%) as males (8.6%). Among females, positive
      relationships were found between specific EAT-26 factors scores and both anxiety
      and depression scores. The emotional antecedents and consequences of binge eating
      and of compensatory activities were compared in three sub-groups of individuals
      who reported recurrent bingeing with loss of self-control during binges. The
      three sub-groups consisted of individuals who reported, 1) bingeing without
      engaging in compensatory activities, 2) bingeing and compensating by means other
      than vomiting (fasting, exercising, or use of laxatives or diuretics), and 3)
      bingeing and compensating by vomiting. Regardless of the type of activity, those
      individuals who engaged in compensatory activities reported greater negative
      affect preceding binge episodes than those who did not compensate. In addition,
      contrary to expectations, negative affect did not decrease, but instead increased
      significantly, following binge episodes and decreased immediately before and
      after compensatory activities.

PMID- 11330494
TI  - Mortality during a famine--Gode district, Ethiopia, July 2000.
AB  - Recurrent famine has been a major cause of mortality in the Horn of Africa. In
      Ethiopia, three consecutive years of drought led to widespread loss of livestock,
      population displacement, and malnutrition, placing an estimated 10 million
      persons at risk for starvation in 2000. A large proportion of the population of
      the Gode district in Somali region was displaced in a search for food and food
      aid (CDC, unpublished data, 2000). From April through July 2000, nongovernmental
      organizations (NGOs) opened feeding centers in the Gode district. Because no
      vital statistics or public health surveillance system existed in the district,
      and no representative mortality or morbidity data were available, during July
      2000, CDC, in collaboration with Save the Children U.S., the Office of Foreign
      Disaster Assistance of the U.S. Agency for International Development, and the
      United Nations Children's Fund (UNICEF), conducted a mortality survey. This
      report summarizes the results of this survey, which found persistently high
      levels of mortality, with measles representing an important cause of mortality in
      children aged <5 years and 5-14 years. Mass measles vaccination with vitamin A
      distribution is an important intervention during the acute phase of famines in
      sub-Saharan Africa.

PMID- 11330495
TI  - Fatal and severe hepatitis associated with rifampin and pyrazinamide for the
      treatment of latent tuberculosis infection--New York and Georgia, 2000.
AB  - One of the recommended treatments for latent tuberculosis infection (LTBI) is a 9
      month regimen of isoniazid (INH); a 2-month regimen of rifampin (RIF) and
      pyrazinamide (PZA) is an alternative in some instances. In September 2000, a man
      in New York died of hepatitis after 5 weeks of RIF-PZA, and in December, a woman
      in Georgia was admitted to a hospital because of hepatitis after 7 weeks of this
      regimen. This report summarizes the findings of the investigations of these
      incidents, which underscore the need for clinical monitoring for adverse effects
      in all patients receiving treatment for LTBI.

PMID- 11330496
TI  - Cluster of tuberculosis cases among exotic dancers and their close contacts-
      Kansas, 1994-2000.
AB  - During January 2001, the Wichita-Sedgwick County Department of Community Health
      (WSCDCH), the Kansas Department of Health and Environment (KDHE), and CDC
      investigated a cluster of tuberculosis (TB) cases that occurred from 1994 to 2000
      among women with a history of working as dancers in adult entertainment clubs
      (i.e., exotic dancers) and persons who were close contacts of exotic dancers.
      This report describes the results of the investigation and illustrates the need
      for early identification of TB clusters through ongoing surveillance and
      resources for health departments to respond rapidly to TB outbreaks.

PMID- 11330497
TI  - Outbreaks of Escherichia coli O157:H7 infections among children associated with
      farm visits--Pennsylvania and Washington, 2000.
AB  - During the spring and fall of 2000, outbreaks of Escherichia coli O157:H7
      infections among school children in Pennsylvania and Washington resulted in 56
      illnesses and 19 hospitalizations. Illness was associated with school and family
      visits to farms where children came into direct contact with farm animals. This
      report summarizes the findings of investigations of these outbreaks (Figure 1)
      and includes strategies to reduce the transmission of enteric pathogens from farm
      animals to children.

PMID- 11330498
TI  - A simple model of holography and some enhanced resolution methods in electron
      microscopy.
AB  - A simple pictorial model of electron interference effects based on an extended
      representation of the autocorrelation function is described and developed. Unlike
      Abbe's theory of transmission imaging, the model incorporates fully the effect of
      the loss of phase that occurs in the detector plane. The aperture transfer
      function and information limit (envelope function) are also incorporated with
      reference to the simplest scattering geometry of Young's slits. The model is then
      applied to holography, the diffraction phase problem, ptychography, Wigner
      distribution deconvolution, conventional bright-field imaging, single side-band
      imaging and tilt-series reconstruction. Some of these methods require an
      understanding of four-dimensional integral functions, but the model reduces the
      problem into a projection of a two-dimensional space. It is hoped that the model
      will help material scientists who are not specialists in imaging and diffraction
      theory to understand some recent developments in advanced super-resolution
      imaging methods.

PMID- 11330499
TI  - Heating of TEM specimens during ion milling.
AB  - Sample heating during preparation of electron-thin specimens for observation in
      transmission electron microscopy (TEM) can produce artefacts which invalidate
      observations. This is particularly true of two-phase materials such as metal
      matrix composites, for which sample cooling with liquid nitrogen cannot be used
      to preserve the substructure during milling. A series of experiments is conducted
      using an age-hardenable aluminium alloy which produces a trace of peak
      temperature attained by TEM specimens during ion milling. It is shown that peak
      temperatures of the order of 650 K can be attained using conventional milling
      parameters; the technique must therefore be used with caution with materials such
      as metal matrix composites. A simplified one-dimensional heat transfer analysis
      of the problem is conducted to show that the most critical parameter is heat
      transfer along the sample holder legs and across interfaces along the heat path.
      Temperature differentials within the TEM specimen are shown to be less
      significant, yet these alone are capable of reaching 60 K within a dimpled
      specimen under usual milling conditions.

PMID- 11330500
TI  - Concentration limits for the measurement of boron by electron energy-loss
      spectroscopy and electron-spectroscopic imaging.
AB  - We have shown that energy-loss spectroscopy in a medium-voltage transmission
      electron microscope can measure concentrations of boron (in a carbon matrix) down
      to 0.2%, with 10% accuracy. The detection limit is determined by electron-beam
      shot-noise statistics and by gain variations in the photodiode or charge-coupled
      diode array.

PMID- 11330501
TI  - Two-dimensional, electrostatic finite element study of tip-substrate interactions
      in electric force microscopy of high density interconnect structures.
AB  - Two-dimensional electrostatic finite element modeling is used to estimate the
      variation of tip force as a function of potential, dielectric film thickness, and
      tip-substrate spacing when imaging using electric force microscopy. Blanket
      dielectric films and approximately 1000 nm thick interconnect structures were
      studied. We conclude that sidewall damage regions can be detected but will
      require special processing to make an unambiguous measurement.

PMID- 11330502
TI  - 4Pi-confocal microscopy of live cells.
AB  - By coherently adding the spherical wavefronts of two opposing lenses, two-photon
      excitation 4Pi-confocal fluorescence microscopy has achieved three-dimensional
      imaging with an axial resolution 3-7 times better than confocal microscopy. So
      far this improvement was possible only in glycerol-mounted, fixed cells. Here we
      report 4Pi-confocal microscopy of watery objects and its application to the
      imaging of live cells. Water immersion of 4Pi-confocal microscopy of membrane
      stained live Escherichia coli bacteria attains a 4.3-fold better axial resolution
      as compared to the best water immersion confocal microscope. The resolution
      enhancement results into a vastly improved three-dimensional representation of
      the bacteria. The first images of live biological samples with an all-directional
      resolution in the 190-280 nm range are presented here, thus establishing a new
      resolution benchmark in live-cell microscopy.

PMID- 11330503
TI  - Surface damage formation during ion-beam thinning of samples for transmission
      electron microscopy.
AB  - All techniques employed in the preparation of samples for transmission electron
      microscopy (TEM) introduce or include artifacts that can degrade the images of
      the materials being studied. One significant cause of this image degradation is
      surface amorphization. The damaged top and bottom surface layers of TEM samples
      can obscure subtle detail, particularly at high magnification. Of the techniques
      typically used for TEM sample preparation of semiconducting materials, cleaving
      produces samples with the least surface amorphization, followed by low-angle ion
      milling, conventional ion milling, and focused ion beam (FIB) preparation. In
      this work, we present direct measurements of surface damage on silicon produced
      during TEM sample preparation utilizing these techniques. The thinnest damaged
      layer formed on a silicon surface was measured as 1.5 nm thick, while an
      optimized FIB sample preparation process results in the formation of a 22 nm
      thick damaged layer. Lattice images are obtainable from all samples.

PMID- 11330504
TI  - Effect of coronary angiography on plasma endothelin-1 and nitric oxide
      concentrations.
AB  - Endothelium takes part in the regulation of vascular tone through the production
      of endothelium-derived relaxing factor, nitric oxide (NO), and the contracting
      factor endothelin-(ET-1). Induction of ET-1 and NO is influenced by many stimuli
      including hypoxia and shear stress. Some of these stimuli may arise during
      coronary angiography (CAG). In this study, the authors aimed to show endothelial
      response in patients undergoing CAG by evaluating plasma ET-1 and NO end-products
      including nitrite and nitrate concentrations. Twenty-four male patients with a
      mean age of 54.3 years (age range: 37-70) were included in the study. The
      patients had no coronary atherosclerotic lesions established by CAG. The mean
      time of the CAG procedures was 24.8 minutes, with a range of 19-33 minutes.
      Immediately before blood sampling, systolic and diastolic blood pressures were
      recorded. The mean blood pressures before and after CAG were 140/90 and 150/95,
      respectively. End products of NO radical, nitrite and nitrate (NOx), in plasma
      were used as a marker for the production of NO radical. ET-1 concentrations were
      measured by ELISA method. Significant increases in ET-1 concentrations were
      observed during CAG while no change observed in NOx concentrations. Duration of
      the CAG procedure was found to be correlated with the percent increase of the
      plasma ET-1 concentrations during CAG (r = 0.45, p<0.05, Figure 1), but not with
      NOx concentrations. Plasma ET-1 concentrations in patients who were cigarette
      smoking were found higher than those of patients who were nonsmokers (1.26 +/-
      0.38 and 2.97 +/- 0.87 fmol/L, respectively). It was concluded that endothelial
      cells show increased ET-1 production as a response of some mechanical or
      emotional stimuli during CAG procedure that may play an important role in the
      regulation of vascular tonicity and some pathological processes. The authors
      suggest that duration and manipulation of CAG may be an important factor in
      plasma ET-1 concentrations.

PMID- 11330505
TI  - Intact insulin, insulin propeptides, and intima-media thickness in the femoral
      artery in 58-year-old clinical healthy men--the Atherosclerosis and Insulin
      Resistance Study.
AB  - The aim of this study was to examine the association between intact insulin,
      insulin propeptides, and femoral artery intima-media thickness. The design was a
      cross-sectional study and the study group (n = 391) consisted of randomly
      recruited clinically healthy 58-year-old Swedish men. The intima-media thickness
      of the common femoral artery was measured with ultrasound. Fasting plasma
      insulin; intact insulin; proinsulin; 32,33 split-proinsulin; and C-peptide
      concentrations were assessed. The results showed that the common femoral artery
      intima-media thickness correlated significantly and univariately with waist-hip
      ratio, systolic blood pressure, serum total cholesterol, high-density lipoprotein
      cholesterol, low-density lipoprotein cholesterol, triglycerides, ApoB, low
      density lipoprotein peak particle size, and cigarette years. Furthermore, of
      intact insulin and insulin propeptides, only intact insulin and C-peptide were
      univariately associated with common femoral artery intima-media thickness (r=
      0.14, p < 0.01; r= 0.18, p < 0.01; respectively). In a multiple regression
      analysis, common femoral artery intima-media thickness was independently
      associated with systolic blood pressure (beta-coefficient = 0.004, p = 0.002),
      ApoB (beta-coefficient = 0.338, p < 0.001 ) and cigarette years (beta-coefficient
      = 0.0004, p < 0.001), (R2= 25%, p<O0.00). In conclusion, smoking, systolic blood
      pressure, and ApoB but not insulin or insulin propeptides were independently
      associated with femoral atherosclerosis.

PMID- 11330506
TI  - Interaction between gene polymorphisms of renin-angiotensin system and metabolic
      risk factors in premature myocardial infarction.
AB  - The renin-angiotensin system is involved in the pathogenesis of coronary artery
      disease (CAD) and myocardial infarction (MI). The authors investigated the
      association of genetic variability in the renin-angiotensin system (RAS) with
      premature MI and interactive effects between gene polymorphisms and metabolic
      risk factors on MI risk. Their study compared 142 patients with MI younger than
      55 years with 142 healthy subjects. Polymorphisms of angiotensin-I converting
      enzyme (ACE) gene (insertion/deletion), angiotensinogen gene (M235T), and
      angiotensin-II type-1 receptor (AGT1R) gene (A1166C) were tested. The ACE-DD
      (deletion/deletion) genotype conferred a twofold independent risk for MI
      (confidence interval [CI] = 1.1-3.7; p = 0.01) after adjustment for
      cardiovascular risk factors, whereas angiotensinogen-TT genotype and AGT1R-AA
      genotype were not independent risk factors for MI. An interactive effect on MI
      risk was found between ACE-DD and AGT1R-AA genotypes (odds ratio [OR]=2, 95% CI=
      1-3.9), between ACE-DD and angiotensinogen-TT genotypes (OR = 2.7, 95% CI = 1
      7.3), as well as among ACE-DD, angiotensinogen-TT, and AGT1R-AA genotypes
      (OR=4.8, 95% CI = 1-22.8). Similarly, metabolic risk factors interacted with
      angiotensinogen-TT genotype (OR= 2, 95% CI = 1.1-3.9) on MI risk. The ACE-DD
      genotype is an independent risk factor for MI in patients younger than 55 years.
      Additionally, the authors provide evidence of an interactive effect on MI risk
      between risk genotypes of RAS, as well as between the angiotensinogen-TT genotype
      and metabolic risk factors.

PMID- 11330507
TI  - The relationship between exercise performance and peripheral circulation in
      patients with peripheral arterial occlusive disease.
AB  - The exercise performance of patients with peripheral arterial occlusive disease
      was often impaired. The relationship of exercise performance, daily physical
      activity, and peripheral circulation was studied. Twenty-five patients with
      peripheral arterial occlusive disease were recruited; their exercise performance
      was evaluated with a maximal graded exercise test. A habitual physical activity
      questionnaire was used to quantify the physical activity level. Measurement of
      peripheral circulation included the assessment of macrocirculation (ankle
      brachial pressure index, calf blood flow by impedance plethysmograph) and
      microcirculation (cutaneous blood flow, cutaneous temperature, transcutaneous
      oxygen tension, and cutaneous blood flow responses to iontophoresis). Pearson's
      product correlation coefficient and multiple linear regression were used in data
      analysis. Results showed that age, sports index in habitual physical activity
      questionnaire, and ankle-brachial pressure index were significantly correlated
      with maximal walking time. Age and sports index were the two major determinants
      for their exercise performance and accounted for a 61.5% variability.

PMID- 11330508
TI  - QTc dispersion measurement for risk of syncope in patients with aortic stenosis.
AB  - The purposes of this study are to evaluate the clinical usefulness of maximum QTc
      and QTc dispersion determination in aortic stenosis, and to compare the effects
      of maximum QTc and QTc dispersion on the risk of syncope in aortic stenosis. The
      QT interval dispersion has long been known to be a marker of dispersion of
      ventricular repolarization and, hence, electrical instability. Additionally, it
      has been shown that these patients have a propensity to ventricular
      tachyarrhythmic syncope. The study included 86 patients with aortic stenosis who
      underwent left-heart catheterization and coronary angiography during
      investigation of syncope and 30 healthy subjects. The patients were characterized
      with regard to the presence or absence of a history of syncope and the severity
      of aortic stenosis (the degree of peak transvalvular gradient). In addition, QT
      max and QT dispersion measurements were corrected for heart rate according to
      Bazett's formula. The QTc max and QTc dispersion were greater in patients with
      aortic stenosis than in the healthy subjects (477 +/- 49 ms vs 370 +/- 22 ms, p <
      0.001; 60 +/- 13 ms vs 38 +/- 1 ms, p < 0.001). Similarly, the QTc max and QTc
      dispersion were greater in the patients with a history of syncope than in the
      patients with no history of syncope (493 +/- 48 ms vs 459 +/- 4 ms, p < 0.001; 68
      +/- 12 ms vs 53 +/- 10 ms, p < 0.001). In addition, both parameters were greater
      in the patients with a high transvalvular gradient than in the patients with a
      low transvalvular gradient (489 +/- 49 ms vs 451 +/- 39 ms, p < 0.001; 65 +/- 12
      ms vs 50 +/- 9 ms, p < 0.001). Multivariate logistic regression analysis showed
      that only a increased QTc dispersion had significant value for the risk of
      syncope in aortic stenosis. An increased QTc dispersion caused a 10.4% increase
      in the occurrence of syncope in aortic stenosis. These results suggest that high
      values of QTc dispersion are sensitive noninvasive markers to determine the risk
      for syncope in aortic stenosis.

PMID- 11330509
TI  - Mitral valve prolapse in patients with pure rheumatic mitral stenosis: an
      angiographic study.
AB  - Of 122 adult patients suspected of having rheumatic mitral stenosis, 112
      fulfilled the hemodynamic and angiographic criteria for pure, isolated mitral
      stenosis. There were 88 females and 24 males with an age range of 16 to 60 years.
      The left ventriculograms (30 degrees right anterior oblique) were subjectively
      assessed for gross bulging of the mitral valve leaflets beyond the mitral fulcrum
      into the left atrium during a beat with maximal opacification. Seventeen percent
      of cases had typical evidence of mitral valve prolapse, which is much higher than
      the 3% to 5% rate reported for the general population. This phenomenon was
      independent of the patients' age, sex, hemodynamic findings, and/or their
      underlying cardiac rhythm, thus implying the direct role of rheumatic mitral
      stenosis in the genesis of secondary mitral valve prolapse.

PMID- 11330510
TI  - Cardiac amyloidosis presenting as microvascular angina--a case report.
AB  - Cardiac amyloidosis usually presents with heart failure, but rarely leads to
      coronary insufficiency. The authors report a case of a 69-year-old Japanese woman
      with cardiac amyloidosis presenting as microvascular angina. She had exertional
      angina with positive exercise test and normal coronary angiograms. However, heart
      failure developed, and she died 3 years after symptom onset. On autopsy, coronary
      arteries were patent. In contrast to that of the epicardial coronary arteries,
      histologic examination of the heart revealed severe obstructive alterations of
      the intramural coronary arteries with amyloid. Furthermore, amyloid was present
      mainly in the endocardium and the intramural coronary arteries, but there was
      little present in the myocardium. This case was a rare AL amyloidosis. There have
      been only 4 reported cases of cardiac amyloidosis that presented with exertional
      angina, a positive exercise test, and normal coronary angiograms and histologic
      examination.

PMID- 11330511
TI  - Acute anterior myocardial infarction following a mild nonpenetrating chest trauma
      -a case report.
AB  - Myocardial infarction in patients under age 45 years is a relatively unusual
      phenomenon; blunt chest trauma is one of the nonatherosclerotic mechanisms
      leading to acute myocardial infarction in young adults. The authors report a rare
      case of anterior myocardial infarction in a 22-year-old man following a mild
      nonpenetrating chest trauma whose left chest was elbowed during a soccer game.

PMID- 11330512
TI  - Use of a Fogarty catheter to open an incompletely expanded Vena Tech-LGM vena
      cava filter--a case report.
AB  - A Vena Tech-LGM 30D/U filter (B. Braun/Vena Tech; Evanston, IL) opened
      incompletely after transjugular placement in the infrarenal vena cava. The
      cephalic points of the stabilizing side rails were open and had engaged the caval
      wall. The base of the filter failed to open. The filter would not successfully
      inhibit the clots and could possibly migrate. The filter base was not placed in a
      clot as shown with intraoperative venography before and after the placement. The
      balloon of a 6F Fogarty catheter was used successfully to dilate the distal legs
      of the filter, and fully expand the base.

PMID- 11330513
TI  - Coronary artery ectasia, aneurysm of the basilar artery and varicose veins:
      common presentation or generalized defect of the vessel wall? A case report.
AB  - A young man who suffered from an acute myocardial infarction is presented. He
      presented coronary artery ectasia along with coronary artery disease. Further
      evaluation revealed the presence of both a saccular aneurysm of the basilar
      artery as well as varicose veins of the lower limbs. A common pathogenic
      mechanism is discussed since all these findings are characterized by similar
      histologic substrate with the most profound defect being destruction of the
      myoelastic elements of the media.

PMID- 11330514
TI  - Wolff-Parkinson-White syndrome mimicking acute anterior myocardial infarction in
      a young male patient--a case report.
AB  - A young male with Wolff-Parkinson-White syndrome whose electrocardiographic
      pattern was suggestive of acute anterior myocardial infarction is described. A 21
      year-old male with a history of ventricular fibrillation after being successfully
      resuscitated was admitted to the coronary care unit. His electrocardiogram showed
      ST elevation in the precordial leads (V1-V6). This condition was erroneously
      interpreted as an acute myocardial infarction. At the fourth day, while ST
      elevations returned to baseline, short PR interval and delta waves were observed
      on the ECG. Myocardial infarction was excluded by biochemical tests,
      echocardiography, and coronary angiography. Electrophysiologic study confirmed
      Wolff-Parkinson-White syndrome with two accessory pathways.

PMID- 11330515
TI  - Regarding "acute ECG changes and chest pain induced by neck motion in patients
      with cervical hernia".

PMID- 11330516
TI  - Serum levels of selenium, manganese, copper, and iron in colorectal cancer
      patients.
AB  - This article describes a study in which four trace elements (Se, Mn, Cu, and Fe)
      were analyzed in the blood serum of the patients with colorectal cancer from the
      Moravian region of the Czech Republic. Atomic absorption spectrometry with
      graphite furnace atomization was used for analysis of selenium and manganese and
      with flame atomization for analysis of copper and iron. The observed serum
      concentrations in adenocarcinoma colorectal patients of selenium were
      significantly lower (41:8 +/- 11.6 microg/L) and those of manganese (16.3 +/- 4.5
      microg/L) and iron (2.89 +/- 1.23 mg/L) were significantly higher as compared to
      the age-matched control group. Copper serum content (0.95 +/- 0.28 mg/L) did not
      significantly differ as compared to healthy population.

PMID- 11330517
TI  - Serum alpha-tocopherol and selenium in Belgian infants and children.
AB  - Previous studies showed low selenium (Se) concentrations in Belgian children.
      Serum alpha-tocopherol, retinol, total cholesterol, high-density lipoprotein and
      low-density lipoprotein cholesterol, selenium (Se), and thiobarbituric acid
      reactive substances were examined. In order to obtain further information on the
      Se status in Belgian children, Se, alpha-tocopherol, retinol, and lipid
      concentrations were examined and signs of peroxidative lipid damage were
      evaluated in a subgroup. The study was performed in 524 children (0-14 yr old)
      during vaccination campaigns. Three age groups were analyzed: 0-1, 1-4, and 4-14
      yr. In 87 of them, where sufficient amounts of serum were available, analysis of
      thiobarbituric acid-reactive substances was done. Infants have high serum alpha
      tocopherol concentrations: (23.2 micromol/L [median and interquartile range: 18.6
      30.2]) and low Se concentrations (0.37 mol/L [0.27-0.47]). Se concentrations rise
      significantly during the first 4 yr (p < 0.0001) (Mann-Whitney U-test, tied p
      values): 0.70 micromol/L (0.59-0.82); in the 4-14 yr olds, it was 0.75 micromol/L
      (0.67-0.86). These values remain low compared to results coming from other parts
      of the world. Alpha-tocopherol concentrations decrease significantly after
      infancy (p < 0.0001). The ratio alpha-tocopherol/total cholesterol is higher in
      infants. This is induced by the high vitamin E content of infant formulas. Signs
      of serum lipid peroxidation could not be detected by analysis of serum
      malondialdehyde concentrations. High alpha-tocopherol concentrations, as those
      observed in infant serum lipids, could be one of the protective mechanisms from
      the peroxidative lipid damages, sometimes observed in a low-Se status.

PMID- 11330518
TI  - Endemic goiter, thiocyanate overload, and selenium status in school-age children.
AB  - Iodine deficiency (ID) and related disorders are still major, yet unresolved
      health concerns. Recently, in a systematic survey of school-age children (SAC),
      we reported severe to moderate ID, in Ankara and three cities from Black Sea
      region of Turkey. The current study attempted to evaluate selenium (Se) status,
      thiocyanate (SCN-) overload, and their possible contribution to the goiter
      endemics and thyroid hormone profile observed in these cities. Thyroid
      ultrasonography was performed and serum Se, SCN(-), thyroid hormones, sensitive
      TSH (sTSH) levels, and, urinary iodine concentrations (UICs) were determined from
      251 SAC (9-11 yr old). Thyroid volumes (TVs) exceeding recommended upper normal
      limits and median UIC indicated goitre endemics and moderate to severe ID in the
      areas studied. Mean serum SCN(-) concentrations were found to be greater than the
      controls from the literature. The UIC/SCN(-) ratio was found to be lowest in
      Bayburt and Trabzon denoting that SCN(-) overload may contribute to the goiter
      endemics. Serum Se concentrations represent a marginal deficiency in the four
      areas studied. No significant correlations between serum Se concentrations and
      the other parameters studied (i.e., TV, SCN(-), thyroid hormones, sTSH, UIC) was
      detected. In conclusion, this study showed that selenium is also marginally
      deficient in the iodine-deficient endemic areas studied, but this has little or
      no impact on the thyroid hormone profile and the goiter endemics. SCN(-) overload
      may contribute to the endemics, especially for the areas where iodine is severely
      deficient. An effective iodine supplementation program will not only resolve the
      goiter endemics but also the consequence of SCN(-) overload as well in the
      endemic goiter areas studied.

PMID- 11330519
TI  - Homogeneity and stability studies on sodium, calcium, magnesium, and manganese in
      human saliva.
AB  - This article reports on the homogeneity and stability of saliva samples treated
      and stored under different conditions. The analytes chosen for this evaluation
      were Na, Ca, and Mg as minor elements and Mn as the trace element. The results
      obtained show that when the sample was homogenized in an ultrasonic bath, a
      minimum volume of 0.25 mL was required to consider the sample homogeneous. The
      stability of the analytes depended on their concentration. The Ca and Mg content
      seemed to be stable for at least 1 wk when the samples were stored at room
      temperature, whereas the Mn content seemed to be unstable for 1 d even when the
      sample was stored at -20 degreesC.

PMID- 11330520
TI  - Clinical laboratory parameters in osteoarthritic knee-joint effusions correlated
      to trace element concentrations.
AB  - Interactions of clinical laboratory parameters with trace elements in knee-joint
      effusions might turn out to be potential diagnostic tool, increasing our
      pathophysiological understanding and knowledge on knee-joint effusions. Thus, the
      11 clinical laboratory parameters, total protein, albumin, glucose, lactate
      dehydrogenase, uric acid, pH, rheumatoid factor, antistreptolysin, C-reactive
      protein, leukocyte, and erythrocyte counts were determined in 39 osteoarthritic
      knee-joint effusions and in corresponding sera. Additionally, concentrations of
      the 17 trace elements barium, beryllium, calcium, cadmium, cesium, copper,
      lanthanum, lithium, magnesium, molybdenum, lead, rubidium, antimony, tin,
      strontium, thallium, and zinc in both effusions and corresponding sera were
      quantified by inductively coupled plasma-mass spectrometry. Concentrations of
      most laboratory parameters in synovial fluid were within the normal ranges for
      serum. However, concentrations of total protein and albumin in effusions were
      distinctly lower than in sera of healthy adults. Results for rheumatoid factor,
      antistreptolysin, and C-reactive protein in the effusions were below their
      corresponding threshold values for serum. An indicator for inflammation, the
      leukocyte count had a median < 6.3 G/L. The erythrocyte count (median: < 0.06
      T/L) revealed a very low presence of red blood cells in the effusions. Total
      protein concentrations and lactate dehydrogenase activity in the effusions
      correlated positively with effusion copper (r = 0.61 and 0.66) and effusion zinc
      (r = 0.71 and 0.49). For cesium, a negative correlation in both sera (r = -0.44)
      and effusions (r = -0.44) with LDH activity could be established. Concentrations
      of rubidium, strontium, and cesium responded to albumin concentrations in sera
      and in effusions, establishing an inverse correlation. All other trace elements
      showed no or only weak associations with the clinical laboratory parameters
      determined. Although distinct relationships between trace element concentrations
      and clinical laboratory parameters in knee-joint effusions exist, the clinical
      relevance of these findings needs to be further elucidated.

PMID- 11330522
TI  - Paleonutritional analysis on the prehispanic population from La Palma (Canary
      Islands).
AB  - In this study, we determine bone strontium, barium, and calcium, as well as zinc,
      copper, and iron, in prehispanic samples belonging to adult individuals from the
      two main funerary caves from La Palma (Espigon and Barranco Porto), comparing
      them with our own modern controls. We have found that the Ba/Sr molar ratio of
      the individuals from Barranco Porto are significantly lower than that of the
      individuals from Espigon, thus suggesting a consumption of a marine-based diet by
      the former.

PMID- 11330521
TI  - Protective role of intraperitoneally administered vitamin E and selenium on the
      antioxidative defense mechanisms in rats with diabetes induced by streptozotocin.
AB  - The aim of this work was to determine the protective effects of intraperitoneally
      administered vitamin E and selenium (as Na2SeO3, Se) on the lipid peroxidation as
      thiobarbituric acid reactive substances (TBARS) and vitamin E levels, glutathione
      peroxidase (GSH-Px), reduced glutathione (GSH) activities in the plasma, red
      blood cell (RBC), liver, and muscle,of rats with streptozotocin-induced diabetes.
      Fifty adult male Wistar rats were used and all rats were randomly divided into
      five groups. The first group was used as a control and the second group as a
      diabetic control. A placebo was given to first and second groups by injection.
      The third group was intraperitoneally administered with vitamin E (20 mg over 24
      h), the fourth group with Se (0.3 mg over 24 h), and the fifth group with vitamin
      E and Se combination (COM) (20 mg vitamin E + 0.3 mg Se over 24 h). This
      administration was done for 25 days and the TBARS, vitamin E, GSH-Px, GSH levels
      in the plasma, RBC, liver, and muscle samples were determined. The vitamin E
      level in the plasma and liver was significantly (p < 0.05) higher in the control
      than in the diabetic control group. Also, the TBARS levels in the RBC, liver, and
      muscle were significantly (p < 0.05) lower in the control than in the diabetic
      control group. However, GSH-Px and GSH activities in RBC, liver, and muscle were
      not statistically different between the control and the diabetic control groups.
      The vitamin E levels in plasma and liver (p < 0.01 and p < 0.001) and GSH-Px
      activities (p < 0.01, p < 0.001) in RBC were significantly higher in vitamin E,
      Se, and COM groups than in both control and diabetic control groups. However, the
      TBARS levels of RBC, muscle, and liver in vitamin E and Se administered groups
      were significantly (p < 0.05-p < 0.001, respectively) decreased. These results
      indicate that intraperitoneally administered vitamin E and Se have significant
      protective effects on the blood, liver, and muscle against oxidative damage of
      diabetes.

PMID- 11330523
TI  - Effect of lanthanide chloride on photosynthesis and dry matter accumulation in
      tobacco seedlings.
AB  - To investigate the physiological effects of rare earth ions, we have studied the
      effect of LaCl3 on the photosynthetic light reactions in tobacco (Nicotiana
      tobacum). When treated with 5-20 mg/L LaCl3 in Hoagland solution by water
      culture, the dry matter accumulation of different parts in tobacco, the content
      of chlorophyll increased gradually, but decreased when the concentration of LaCl3
      was > or = 50 mg/L. The optimum concentration for growth appeared to be about 20
      mg/L of LaCl3 in nutrient solution. La3+ promoted the activities of the Hill
      reaction, Mg2(+)-ATPase, and stimulated the rate of photophosphorylation in
      chloroplast at low concentrations, but inhibited them at high concentrations. It
      is concluded that La3+ stimulated the growth of tobacco seedlings and accelerated
      the photosynthetic light reactions at suitable concentration in vivo.

PMID- 11330524
TI  - Multianalysis of trace elements in mosses with inductively coupled plasma-mass
      spectrometry.
AB  - As a part of an air-pollution biomonitoring survey, a procedure using inductively
      coupled plasma-mass spectrometry (ICP-MS) and microwave digestion was developed
      to achieve a high sample throughput and guarantee the accuracy of the results.
      This article presents an analytical method to measure 22 trace elements. As, Ba,
      Cd, Ce, Co, Cr, Cs, Cu, Fe, Hg, La, Mo, Ni, Pb, Rb, Sb, Sr, Th, Tl, U, V, W were
      analyzed in 563 mosses collected in France. The digestion was performed in
      polytetrafluoroethylene (PTFE) vessel using the mixture HNO3-H2O2-HF. The data
      were reprocessed taking into account the drift curve calculated for each element.
      The detection limits (DL) calculation was based on the standard deviations of the
      reagent blanks concentrations. The DL varied from one batch to another, because
      of the heterogeneity of the mosses' elemental contents. The DL ranged between
      0.001 microg/g (Cs, Tl) and 70 microg/g (Fe) and were mainly around 0.01 microg/g
      (As, Cd, Ce, Co, Hg, La, Mo, Sb, Sr, U, V, W). The detection limits obtained were
      in agreement with the concentrations observed in the samples, except for Hg and
      Ni. The reproducibility between duplicates and the analytical precision were near
      10%. The procedure was tested with the mosses' reference materials.

PMID- 11330525
TI  - Isolation and characterization of rare earth element-binding protein in roots of
      maize.
AB  - Rare earth element-binding protein was isolated from maize, which was grown under
      greenhouse conditions and characterized in terms of molecular weight, amino acid
      composition, and ultraviolet absorption. The molecular weight of the maize
      protein was determined to be 183,000, with two distinct subunits of approximately
      molecular weights of 22,000 and 69,000, respectively. The protein is particularly
      rich in asparagine/aspartic acid, glutamine/glutamic acid, glycine, alanine, and
      leucine and contains 8.0% of covalently bound carbohydrate. The ultraviolet
      absorption of the protein is low at 280 nm and no change in the adsorption was
      observed with a change in pH. Compared to the unique features of the
      metallothioneins with a molecular weight of approximately 10,000, a high cysteine
      content of 30%, high absorption at 254 nm and a low absorption at 280 nm, and
      absorption change with pH, the REE-binding protein is unlikely to be plant
      metallothionein in nature. It was found that an almost twofold greater
      concentration was found for most of the REEs in the protein isolated from the
      maize with REE fertilizer use than that without REE fertilizer. This study
      suggests that the REE-binding protein is a glycoprotein and REEs can be firmly
      bound with the protein of maize roots.

PMID- 11330526
TI  - Urinary selenium excretion in patients with cervical uterine cancer.
AB  - In this work, we report on a relationship between urinary selenium and the
      development of cervical uterine cancer. A simple chemical method was developed to
      concentrate trace amounts of selenium from relatively large urine samples by use
      of small activated carbon filters. When these filters are irradiated with thermal
      neutrons, selenium can be determined either by 77mSe (t1/2 = 17.5 s) or 75Se
      (t1/2 = 120 d). In this article, we report the results for 82 urine samples from
      women with cervical uterine cancer in several stages of development and from
      healthy controls. These results show a statistically significant increase of
      selenium excretion in cancer patients as compared to controls. Urinary selenium
      excretion is highest for patients in the intermediate stages of the disease.

PMID- 11330527
TI  - Fine-needle aspiration biopsy--new application for an old technique.

PMID- 11330528
TI  - Cytomegalovirus and renal allograft rejection.

PMID- 11330529
TI  - Transplant tolerance--the holy grail.

PMID- 11330530
TI  - Increased cysteine plasma levels in kidney transplants: a potential vascular
      disease risk factor?

PMID- 11330531
TI  - Pretransplantation prognostic testing on damaged kidneys during ex vivo warm
      perfusion.
AB  - BACKGROUND: Further expansion of the donor pool with ischemically damaged kidneys
      will be predicated on the ability to develop prognostic testing. Using a well
      established canine autotransplantation injury model, we assessed whether actual
      restoration of renal metabolism by ex vivo warm perfusion could be used to
      predict the status of an organ before transplantation. METHODS: Kidneys were
      subjected to 30 min of warm ischemia followed by 24 hr of static storage in
      ViaSpan at 4 degrees C. After warm ischemia and static storage the kidneys were
      transitioned to 3 hr of warm perfusion using Exsanguinous Metabolic Support
      technology. During this period, parameters indicative of renal metabolism and
      vascular function were used to predict outcomes prospectively. Parameters
      included measures of oxidative metabolism, perfusion characteristics, and
      vascular condition. A Viability Score (VS) was calculated as the sum of the three
      parameters mentioned above. Results were grouped by a VS>2 and a VS<2. RESULTS: A
      clear association between the severity and duration of graft dysfunction and the
      VS was observed. Organs with a VS>2 had a significantly milder period of acute
      tubular necrosis, with both a less severe rise in serum creatinine (mean of 4.4
      vs. 11 mg/dl) and a shorter recovery period (mean of 8 vs. 18 days) than those
      with a VS<2. CONCLUSIONS: Results indicate the possibility of utilizing warm
      perfusion to evaluate kidneys before transplantation. The VS developed
      demonstrated efficacy in classifying the severity of the acute tubular necrosis
      and the occurrence of primary nonfunction, offering a sensitive assay for
      prospective organ testing.

PMID- 11330532
TI  - Cellular distribution of thrombomodulin as an early marker for warm ischemic
      liver injury in porcine liver transplantation: protective effect of prostaglandin
      I2 analogue and tauroursodeoxycholic acid.
AB  - BACKGROUND: Warm ischemia of the graft from non-heart-beating donors is
      considered a risk factor for posttransplant graft dysfunction. The early
      administration of cytoprotective agents may help improve graft dysfunction.
      METHODS: Four groups of 10 pigs each underwent orthotopic liver transplantation.
      Prostaglandin I2 analogue, OP-41483, was administered intraportally 30 min before
      warm ischemic insult in donors and after reperfusion in recipients in one group.
      In the other study group, additional intravenous tauroursodeoxycholic acid (TUDC)
      was given before the warm ischemic insult in donors and after reperfusion, then
      maintained continuously until postoperative day (POD) 7. RESULTS: Exposure of
      liver grafts to warm ischemia resulted in severe congestion with the
      disappearance of thrombomodulin (Tm) from the sinusoidal endothelial cells (SECs)
      and smooth muscle cells (SMCs) around biliary epithelial cells (BEpCs) 2 hr after
      reperfusion, followed by positive immunoreactivity of Tm in BEpCs with
      hyperbilirubinemia, which was related to high mortality. Combined administration
      of OP-41483 and TUDC had a protective effect, demonstrated by sustained
      immunoreactivity of Tm from SECs and SMCs until POD 7, without that reactivity in
      BEpCs. This was associated with reduced congestion and hyperbilirubinemia,
      similar to the control group not subjected to warm ischemia. CONCLUSIONS: These
      findings suggest that negative immunoreactivity of Tm in SECs and SMCs
      surrounding BEpCs and positive in BEpCs may be an early marker for ischemic liver
      injury, and that OP-41483 and TUDC may protect against the microcirculatory and
      biliary derangement.

PMID- 11330533
TI  - Passive transfer of alloantibodies restores acute cardiac rejection in IgKO mice.
AB  - BACKGROUND: Alloantibody is an intrinsic component of the immune response to
      organ transplants. Although alloantibodies have been correlated with decreased
      graft survival, the mechanisms of alloantibody-mediated injury remain largely
      undefined in vivo. In the present study, we have established a model of
      alloantibody-mediated graft injury using B10.A (H-2a) hearts transplanted to wild
      type (WT) or immunoglobulin knock out (IgKO) C57BL-Igh-6 (H-2b) mice. METHODS:
      Alloantibodies were measured in the circulation and graft by flow cytometry and
      in immunofluorescence staining, respectively. Intragraft cytokine mRNA expression
      was evaluated using a competitive template reverse transcriptase polymerase chain
      reaction (RT-PCR) technique. P-selectin and von Willebrand factor expression were
      localized by immunoperoxidase staining. The capacity of alloantibodies to restore
      acute cardiac allograft rejection was tested by passive transfer of monoclonal
      antibodies (mAbs) against donor major histocompatibility complex (MHC) class I
      antigens to IgKO recipients. RESULTS: B10.A cardiac allografts are rejected
      acutely by WT C57BL/6 recipients, but over 50% of the cardiac allografts survived
      more than 50 days after transplantation in IgKO mice. Competitive template RT-PCR
      on the cardiac transplants demonstrated similar levels of IL-1-alpha, IL-12
      (p40), TNF-alpha, IL-2, IFN-gamma, IL-4, and IL-10 mRNA in WT and IgKO recipients
      8-10 days after transplantation, indicating that macrophage- and T-cell-dependent
      immune responses were intact in IgKO recipients. The rejection of B10.A hearts in
      WT recipients was characterized by interstitial and perivascular cellular
      infiltration; IgG, IgM, and complement (C3) deposition; vascular cell injury and
      intravascular platelet aggregation; and release of von Willebrand factor and P
      selectin. In IgKO recipients the lower degree of vascular injury in the absence
      of alloantibody responses was reflected by the lack of release of von Willebrand
      factor and P-selectin, which remained confined to cytoplasmic storage granules of
      endothelial cells and platelets. Acute rejection of cardiac allografts was
      restored to IgKO recipients by passive transfer of proinflammatory IgG2b mAbs
      against donor MHC; recipients injected with isotype-matched control mAbs did not
      reject. In contrast, passive transfer of IgG1 mAbs against donor MHC failed to
      restore acute rejection of cardiac allografts to IgKO recipients. Passive
      transfer of IgG2b, but not IgG1 mAbs was associated with endothelial cell
      activation and plate. let aggregation together with the release of preformed von
      Willebrand factor and P-selectin from storage granules. CONCLUSIONS: Acute
      rejection of cardiac allografts can be reconstituted in IgKO recipients by
      passive transfer of IgG2b, but not IgG1 antibody. This model allows the mechanism
      of alloantibody-mediate graft injury to be dissected in vivo.

PMID- 11330534
TI  - Fine-needle aspiration biopsy allows early detection of acute rejection in
      children after renal transplantation.
AB  - analysis detected rejections often before clinical signs. Half of the patients
      had increased serum creatinine concentration and 38% had fever at the time of
      rejection diagnosis. Both signs were present in only 19% of the episodes. A
      decrease in urine output (>20%) was seen in a third of the episodes. The
      rejections responded well to oral methylprednisolone (3 mg/kg/day), and
      lymphoglobulins were needed in only 12% of the episodes. More than 90% of the
      rejections were completely reversible and no transplant was lost because of acute
      rejection. CONCLUSION: The results indicate that FNAB is a safe and sensitive
      method for the diagnosis and follow-up of acute cellular rejection in pediatric
      recipients of different ages.

PMID- 11330535
TI  - Continuous beta-lactam antibiotic therapy in a double-lung transplanted patient
      with a multidrug-resistant Pseudomonas aeruginosa infection.
AB  - BACKGROUND: It is well known that the bactericidal effect of beta-lactam
      antibiotics is closely related to the time which the serum concentration of the
      antibiotic remains above the minimal inhibitory concentration of the target
      pathogen. Thus, the optimal administration of beta-lactam antibiotics would be
      the continuous infusion of the drug. METHODS: We present a case report with a
      critically ill double-lung transplanted patient with pneumonia due to a multidrug
      resistant Pseudomonas aeruginosa who received continuously 8 g meropenem/24 hr.
      Based on a previous pharmacokinetic study showing that continuous infusion of
      meropenem is at least equivalent to intermittent administration this case report
      is reported to demonstrate the clinical efficacy of continuous infusion. RESULTS:
      C-reactive protein and pneumonia decreased rapidly when clinical conditions were
      improved significantly. Continuous administration of meropenem did not interfere
      with cyclosporine, no side effects were seen, and the patient's renal function
      was not impaired during the whole period of treatment. CONCLUSION: The continuous
      administration of beta-lactam antibiotics is a powerful application in critically
      ill patients to intensify antimicrobial therapy.

PMID- 11330536
TI  - High cysteine levels in renal transplant recipients: relationship with
      hyperhomocysteinemia and 5,10-MTHFR polymorphism.
AB  - BACKGROUND: Long-term survival of renal transplant recipients seems to be
      influenced by the occurrence of thromboembolic complications and cardiovascular
      disease. Preliminary data available in the literature found high levels of
      cysteine (Cy) as a risk factor for deep venous thrombosis independently of high
      homocysteine (tHcy) levels, but no data are available about Cy levels in renal
      transplant recipients. METHODS: To investigate Cy, tHcy, and plasminogen
      activator inhibitor-1 (PAI-1) levels and the prevalence of 5,10
      methylenetetrahydrofolate reductase (MTHFR) in renal transplantation, we studied
      70 stable renal transplant recipients and 66 age- and sex-matched normal subjects
      as controls. RESULTS: Cy, tHcy, and PAI-1 levels were significantly higher in
      renal transplant recipients with respect to controls (Cy: 254 micromol/L [117
      466] vs. 198 micromol/L [99-331], P<0.001; tHcy: 17.0 micromol/L [4.0-68] vs. 8.1
      micromol/L [2.0-24.0], P<0.00001; PAI-1: 16.8 IU/ml [5.1-45.5] vs. 7.9 IU/ml [4.0
      18.0], P<0.00001). High Cy levels were detected in 35.8% of patients.
      Hyperhomocysteinemia, both in the fasting state and postmethionine loading test,
      was diagnosed in 90% of cases. The odds ratios for Cy and tHcy levels within the
      fourth quartile with respect to the other quartiles were markedly increased in
      renal transplant recipients even after adjustment for prevalent cardiovascular
      risk factors, glomerular filtration rate, tHcy and, Cy, respectively (Cy: 29.0
      micromol/L [95% CI 7.0-111]; tHcy: 29.9 micromol/L [95% CI 7.5-118.1]). Fasting
      tHcy levels correlated well with PAI-1 (r=0.65; P<0.0001) but not with Cy levels
      (r=0.10; P=0.4). The prevalence of the MTHFR 677TT genotype in renal transplant
      recipients was not significantly higher in patients than in controls (mutant
      allele frequency: 0.48 in patients and 0.47 in controls) and was associated with
      significantly higher fasting and postmethionine tHcy levels both in controls and
      patients. After 2 months of vitamin supplementation, tHcy (Pre: 17.0 micromol/L
      [4.0-68]; Post: 7.5 micromol/L [2.3-21.9]; P<0.0001) and PAI-1 levels (Pre: 16.8
      IU/ml [5.1-45.5]; Post: 10 IU/ml [2.0-25]; P<0.001) were significantly decreased,
      whereas Cy levels showed a small decrease that did not reach statistical
      significance (Pre: 254 micromol/L [117-466]; Post: 209 micromol/L [168-300];
      P=0.3). Patients with the MTHFR 677TT genotype had the major percentage of
      decrease of tHcy levels with respect to the other genotypes. CONCLUSION: In
      conclusion, this study demonstrates the presence of elevated Cy plasma levels in
      renal transplant recipients. Vitamin supplementation reduces tHcy but not Cy
      levels, and the amount of decrease seems to be influenced by the MTHFR genotype.

PMID- 11330537
TI  - Sequential monitoring of peripheral T-lymphocyte cytokine gene expression in the
      early post renal allograft period.
AB  - BACKGROUND: Despite numerous studies, the precise role of cytokines in acute
      renal allograft rejection remains unclear. In this study we have monitored
      sequential changes in peripheral T cell cytokine gene expression, correlating the
      changes with clinical events after adult renal transplantation, to provide a
      deeper insight of the role of cytokines in allograft rejection. METHODS:
      Sequential changes in peripheral Th-1 [interleukin- (IL) 2 and interferon-gamma]
      and Th-2 (IL-4, IL-5, IL-10, and IL-13) cytokine gene expression in 43 patients
      with (n=15) and without (n=28) episodes of biopsy-proven rejection was monitored
      in the first 6 weeks after renal transplantation using a sensitive, semi
      quantitative reverse-transcriptase polymerase chain reaction ELISA approach.
      RESULTS: Th-2 cytokines: IL-5 and IL13 expression increased before and during
      acute rejection, and decreased after successful antirejection therapy. A
      significant fall in IL-4 expression after transplantation and subsequent return
      to its baseline level of expression was observed in both nonrejectors and
      rejectors. IL-10 showed persistently high expression in nonrejectors, but in
      rejectors the expression fell during acute rejection, with a subsequent rise
      after antirejection therapy. Th-1 cytokines: IL-2 and IFN-gamma decreased in
      expression in the first week posttransplant in the rejectors, at the time of
      acute rejection (IL-2 only) and immediately after completion of antirejection
      therapy. CONCLUSIONS: Sequential monitoring of peripheral T cell cytokine gene
      expression after renal transplantation detected changes in expression that
      correlated with episodes of acute rejection and response to antirejection
      therapy. This approach may be applicable in the clinical laboratory for
      monitoring posttransplant changes in T cell alloreactivity and immunosuppression.

PMID- 11330538
TI  - Impairment of microcirculation in the early reperfusion period predicts the
      degree of graft pancreatitis in clinical pancreas transplantation.
AB  - BACKGROUND: Graft pancreatitis is thought to be induced by ischemia/reperfusion.
      Animal experiments have suggested that an impaired microcirculation is crucial in
      this process. We have therefore studied the relevance of microcirculation in
      clinical pancreas transplantation. METHODS: In 17 patients undergoing pancreas
      transplantation, tissue pO2 was monitored continuously by an electrode implanted
      into the pancreatic tail. A catheter was inserted in the distal part of the
      splenic vein of the pancreas graft. After reperfusion blood samples were taken
      from this catheter and blood flow was measured by the venous outflow method. The
      degree of graft pancreatitis was assessed by peak-C-reactive protein (CRP)
      defined as highest CRP within 3 days after transplantation. RESULTS: Tissue pO2
      increased within 5 min after reperfusion. Thereafter, in most patients a
      transient decrease was noted, indicating impairment of nutritive perfusion.
      During this period there was an increasing negative correlation between peak-CRP
      and tissue pO2 which was highly significant at 60 min after reperfusion (r=-0.70,
      P<0.002). Also donor age correlated significantly with peak-CRP (r=0.64, P<0.005)
      and to a somewhat lesser extend with tissue pO2 60 min after reperfusion (r= 
      0.55, P<0.03). CONCLUSION: These data show that the degree of organ damage in
      clinical pancreas transplantation is directly related to an impairment of
      microcirculation in the early reperfusion period. These data also support the
      idea that grafts from older donors have a higher probability to develop graft
      pancreatitis and that this might be due to an increased incidence of
      microcirculatory disturbances in these organs.

PMID- 11330539
TI  - Cytomegalovirus infection and graft rejection in renal transplantation.
AB  - BACKGROUND: Cytomegalovirus (CMV) infection and CMV disease have been associated
      with acute and chronic graft rejection. The introduction of the sensitive CMV
      antigenemia pp65 assay for detection of CMV infection allowed us to study the
      time course of CMV infection and acute rejection and the long-term outcome in
      renal transplant recipients with and without a CMV risk constellation. METHODS:
      Prospective single center study including 48 renal transplant recipients at risk
      for CMV infection (donor and/or recipient CMV seropositive) and a control group
      of 36 CMV seronegative recipients of CMV seronegative kidney donors. Evidence of
      CMV infection was monitored by the CMV antigenemia pp65 assay every 1 to 2 weeks
      and compared with the occurrence of acute rejection in the posttransplant period
      and graft function at 5 years. RESULTS: CMV infection developed in 83% (40/48) of
      patients of the CMV risk group within 4 months posttransplant. A total of 18 of
      patients experienced an acute rejection episode (control group 16/36; P=0.65). In
      12/18 CMV infection followed rejection and in three patients antigenemia preceded
      the diagnosis of rejection. In three patients CMV antigenemia remained negative.
      Five-year follow up: Patient survival (44/48 vs. 31/36; P=0.48), graft survival
      (38/48 vs. 27/36; P=0.79), number of patients with at least one acute rejection
      episode: CMV risk group: 42.1%, control group 51% (P=0.46), serum creatinine: CMV
      risk group:130 +/- 66 micromol/iter, control group: 126 +/- 37 micromol/ liter
      (P=0.56), proteinuria: CMV risk group: 0.02 +/- 0.02 g/mmol creatinine, control
      group: 0.02 +/- 0.02 g/mmol creatinine (P=1.0). CONCLUSION: CMV infection within
      4 months posttransplant, as defined by a positive antigenemia assay was not found
      to be a risk factor for acute graft rejection or chronic graft dysfunction at 5
      years.

PMID- 11330540
TI  - Uni- and multi-variate analysis of risk factors for early and late hepatic artery
      thrombosis after liver transplantation.
AB  - BACKGROUND: Hepatic artery thrombosis (HAT) is a significant cause of morbidity
      after liver transplantation. The aims of this study are to identify and compare
      risk factors that might contribute to HAT. METHODS: A total of 424 liver
      transplants performed at the University of Virginia were reviewed. HAT was
      defined as complete disruption of arterial blood flow to the allograft and was
      identified in 29 cases (6.8%). HAT was classified as early (less than 1 month
      posttransplant, 9 cases: 2.1%) or late (more than 1 month posttransplant, 20
      cases: 5.4%). Possible risk factors for HAT were analyzed using Pearson chi2 test
      for univariate analysis and logistic regression for multivariate analysis.
      RESULTS: Multiple transplants, recipient/donor weight ratio >1.25, biopsy-proven
      rejection within 1 week of transplant, recipient negative cytomegalovirus (CMV)
      status, arterial anastomosis to an old conduit (defined as a previously
      constructed aorto-hepatic artery remnant using donor iliac artery), and CMV
      negative patients receiving allograft from CMV positive donors were found to be
      significant risk factors for developing early HAT. After logistic regression,
      factors independently predicting early HAT included arterial anastomosis to an
      old conduit [odds ratio (OR)=7.33], recipient/donor weight ratio >1.25 (OR=5.65),
      biopsy-proven rejection within 1 week posttransplant (OR=2.81), and donor
      positive and recipient negative CMV status (OR=2.66). Female donor, the
      combination of female donor and male recipient, recipient hepatitis C-related
      liver disease, donor negative CMV status, and the combination of recipient CMV
      negative and donor CMV negative were found to be significant risk factors for
      late HAT. Factors independently predicting late HAT by logistic regression
      included negative recipient and donor CMV status (OR=2.26) and the combination of
      a female donor and male recipient (OR=1.97). CONCLUSION: Therefore, in
      nonemergency situations attention to these factors in donor allocation may
      minimize the possibility of HAT.

PMID- 11330541
TI  - Low rate of acute lung allograft rejection after the use of daclizumab, an
      interleukin 2 receptor antibody.
AB  - BACKGROUND: The incidence and the severity of acute lung allograft rejection has
      been linked to the development of bronchiolitis obliterans syndrome. Therefore,
      we investigated the effects of daclizumab, a humanized monoclonal antibody
      directed against the alpha subunit of the interleukin 2 receptor, in reducing
      acute rejection after transplantation. METHODS: We retrospectively evaluated 27
      patients who received daclizumab as induction immunosuppression and compared them
      with a historical control group of 34 patients. Both groups received similar
      immunosuppressive regimens involving tacrolimus, prednisone, and either
      azathioprine or mycophenolate mofetil. All patients received cytomegalovirus and
      aspergillus prophylaxis. RESULTS: Twenty-one patients in the control group and 22
      patients in the daclizumab group were available for analysis at 6 months after
      lung transplantation. Ten (48%) patients in the control group had at least grade
      2 acute rejection compared with four (18%) in the daclizumab group (P<0.04). The
      incidence of infection was similar in both groups. One patient in each group
      developed posttransplant lymphoproliferative disease. CONCLUSION: Therapy with
      daclizumab resulted in a significant decrease in the incidence of grade 2 or
      greater acute rejection after lung transplantation compared with historical
      controls. There seems to be no increase in the incidence of adverse effects in
      the patients treated with daclizumab.

PMID- 11330542
TI  - Activated caspase-1 is not a central mediator of inflammation in the course of
      ischemia-reperfusion.
AB  - BACKGROUND: Upon transplantation, donor organs subjected to prolonged ischemia
      suffer from reperfusion injury. Recent observations suggest that caspase
      activation is involved in inducing the deleterious inflammatory reaction that
      mediates reperfusion injury. Release of cytokines like interleukin (IL)-1 and IL
      18 may occur during apoptosis through activation of caspase-1/IL-1beta-converting
      enzyme. We hypothesized that caspase-1 activation is a key event in apoptosis/
      caspase-dependent inflammation during the development of renal reperfusion
      injury. METHODS: Caspase-1-/-, caspase-1+/+ as well as Swiss mice were subjected
      to 45 min of renal ischemia and 24 hr of reperfusion. Animals were administered
      agents capable of neutralizing the pro-inflammatory activation products of
      caspase-1 (IL-1 receptor antagonist, anti-IL-1 receptor antibody, and anti-IL-18
      antibody). The extent of renal functional deterioration, inflammation, and
      apoptosis were compared. RESULTS: No improvement in renal function as reflected
      by serum ureum and creatinine were found in caspase-1-/- mice as compared to wild
      type controls. Caspase-1-/- mice showed slightly attenuated renal inflammation as
      indicated by decreased renal neutrophil influx, but failed to show changes in
      intrarenal tumor necrosis factor-alpha production. Moreover, caspase-1-/- mice
      clearly exhibited reperfusion-induced apoptosis as reflected by renal terminal
      deoxynucleotidyltransferase histology and internucleosomal DNA cleavage.
      Treatment with IL-1 receptor antagonist, anti-IL-1 receptor antibody, or anti-IL
      18 antibody minimally reduced renal functional deterioration, inflammation, and
      apoptosis. CONCLUSIONS: These findings suggest that activated caspase-1 and its
      inflammatory products are involved in, but not crucial to, the induction of
      inflammation after renal ischemia-reperfusion. Hence, apart from caspase-1, other
      (combinations of) activated caspases are likely to be more prominently involved
      in renal reperfusion injury.

PMID- 11330543
TI  - Rapid decreases in donor-specific cytotoxic T lymphocyte precursor frequencies
      and graft outcome after liver and lung transplantation.
AB  - BACKGROUND: A decrease in donor-specific T cell precursor frequencies as seen
      late, one or more years, after transplantation is assumed to reflect
      transplantation tolerance, a condition important for long term acceptance of the
      allograft. However, such late decreases also occur in recipients that developed
      chronic transplant dysfunction questioning its relevance in transplantation
      tolerance. We investigated whether early, i.e., the first 6 months, decreases in
      donor-specific T cell precursor frequencies reflect transplantation tolerance and
      predict graft outcome after liver and lung transplantation. METHODS: Donor and
      third party specific cytotoxic (CTLp) and helper T lymphocyte precursor (HTLp)
      frequencies were analyzed in pretransplant and 1 (or 2) and 6-month blood samples
      taken from liver and lung recipients and were correlated with graft outcome.
      RESULTS: In liver allograft recipients with good graft function (n=7), mean donor
      specific CTLp frequencies decreased as early as 1 month after transplantation and
      remained low thereafter. In contrast, mean CTLp frequencies did not decrease in
      liver allograft recipients with chronic transplant dysfunction (n=6). In lung
      allograft recipients, donor-specific CTLp frequencies remained relatively high
      and frequencies were not different between recipients without (n=6) or with (n=6)
      chronic transplant dysfunction. Donor-specific HTLp frequencies did not change
      significantly after liver or lung transplantation and did not differ between
      recipients without or with chronic transplant dysfunction. CONCLUSIONS: An early
      decrease in donor-specific CTLp correlates with good graft outcome after liver
      transplantation. Such rapid decreases in alloreactivity do not occur after lung
      transplantation illustrating the unique capacity of liver allografts to induce
      transplantation tolerance.

PMID- 11330544
TI  - STAT5 pathway: target of anti-CD4 antibody in attenuation of IL-2 receptor
      signaling.
AB  - BACKGROUND: Anti-CD4 antibodies induce long-term graft survival by incompletely
      understood mechanisms, and CD4-ligation with HIV gp120-derivatives attenuates
      interleukin (IL)-2 receptor signaling. We examined the latter in the context of
      the CD4-modulating antibody 16H5. MATERIALS AND METHODS: We performed immunoblots
      to assess the IL-2-induced phosphorylation of signal transducer and activator of
      transcription (STAT)5 and Akt in the presence or absence of 16H5. Furthermore, we
      documented the effects of 16H5 on the induction of STAT5, activating protein (AP)
      1, and myc by IL-2 in DNA-binding assays. 3H-thymidine incorporation of the human
      lymphoid cell line CMO, which exhibits constitutive activation of the STAT5
      pathway and IL2-independent growth, was also measured during 16H5 treatment.
      RESULTS: In human T lymphocytes, 16H5 attenuated both the tyrosine
      phosphorylation of STAT5 by IL-2 and the IL-2-induced DNA-binding of this
      transcription factor. In contrast, 16H5 had no effect on the serine
      phosphorylation of Akt by IL-2 or on the IL-2-induced DNA-binding of myc. Signal
      transduction involving AP-1 was unaffected by 16H5 and IL-2. 16H5 also attenuated
      CMO cell proliferation. CONCLUSIONS: 16H5 targets the STAT5 signaling pathway to
      attenuate IL-2 receptor signal transduction in human T cells. This observation
      provides a molecular explanation for the immunomodulatory actions of anti-CD4
      antibodies.

PMID- 11330545
TI  - Vaccinia virus complement control protein is capable of protecting
      xenoendothelial cells from antibody binding and killing by human complement and
      cytotoxic cells.
AB  - BACKGROUND: Vaccinia virus complement control protein (VCP) was the first
      secretory microbial protein shown to have structural similarity to the family of
      complement control proteins. VCP can block both the classical and alternate
      complement pathways. Recently, VCP has been shown to bind to heparin, and this
      property contributes to separate functions, making the molecule a multifunctional
      protein. METHODS: VCP prepared from a natural infection of RK-13 cells with
      vaccinia virus was purified to homogeneity. Cultured pig aortic endothelial cells
      (PAECs) were mixed with human serum, anti-Gal alpha1,3 Gal antibody, neutrophils,
      or natural killer (NK) cells in the presence or absence of VCP and either direct
      binding of FITC-labeled antibody or killing by cytotoxic cells was estimated.
      RESULTS: Our cell culture studies demonstrate that VCP blocks complement-mediated
      killing of PAECs by human serum in a dose-dependent manner. We also demonstrate
      that VCP is capable of blocking Gal alpha1,3 Gal binding sites on PAECS.
      Surprisingly, VCP effectively blocked interactions between PAECs and cytotoxic
      cells such as human naive neutrophils and NK cells. CONCLUSION: VCP is a novel
      protein amongst the complement control protein family and can, not only block
      xenorejection by inhibiting complement but also by blocking killing by cytotoxic
      cells.

PMID- 11330547
TI  - Congestion of right liver graft in living donor liver transplantation.
AB  - BACKGROUND: Left liver graft from a small donor will not meet the metabolic
      demands of a larger adult recipient. One solution to this problem is to use a
      right liver graft without a middle hepatic vein (MHV). However, the need for
      drainage from the MHV tributaries has not yet been described. METHODS: Five right
      liver grafts without a MHV were transplanted in patients including two hepatitis
      B virus-cirrhosis, two fulminant hepatic failure and one secondary biliary
      cirrhosis. The graft weight ranged from 650 to 1,000 g, corresponding to 48 to
      83% of the standard liver volume of the recipients. RESULTS: Two of five
      recipients were complicated with severe congestion of the right median sector
      immediately after reperfusion, followed by prolonged massive ascites and severe
      liver dysfunction. One of the patients died of sepsis with progressive hepatic
      dysfunction 20 days after the operation. CONCLUSIONS: Preservation and
      reconstruction of the MHV tributaries is recommended to prevent congestion of the
      right liver graft without MHV.

PMID- 11330546
TI  - The effect of CD28/B7 blockade on alloreactive T and B cells after liver cell
      transplantation.
AB  - BACKGROUND: Hepatocyte cell lines are beginning to be developed as universal
      donors for isolated liver cell transplantation, which is a less invasive method
      than orthotopic liver transplantation for treatment of metabolic liver disease.
      The immune response to isolated liver cell transplantation and its modification
      by costimulatory blockade are as yet not well delineated. METHODS: Adenovirus
      expressing CTLA4Ig was used to study blockade of the costimulatory CD28/B7
      pathway in murine models of hepatocyte transplantation, and the effects on
      alloreactive T and B cells were studied. RESULTS: CTLA4Ig delayed rejection of
      subcutaneously administered C57L-derived murine hepatoma cells in CBA/J
      recipients for >50 days. Activation and cytokine secretion by allospecific CD4+
      and CD8+ T cells were initially blocked by CTLA4Ig; delayed rejection was
      associated with tumor infiltration by CD8+ T cells that did not secrete
      interferon-gamma. CTLA4Ig failed to block transplant rejection in primed mice,
      indicating that memory effector T cells were resistant to its action. In
      contrast, CTLA4Ig suppressed both naive and memory alloreactive B cells. High
      levels of CTLA4Ig mediated acceptance of hepatoma cells delivered directly into
      the spleen. However, isolated primary C57BL/6 mouse hepatocytes delivered into
      the spleen were rejected with only moderately delayed kinetics. CONCLUSIONS:
      Transplant antigenicity, transplant site, and CTLA4Ig dose all affected the
      survival of transplanted liver cells. CD8+ T cells are significant mediators of
      hepatocyte transplant rejection and are relatively resistant to costimulatory
      blockade with CTLA4Ig. Strategies to specifically antagonize CD8+ T cells or to
      modulate MHC class I expression in association with costimulatory blockade by
      CTLA4Ig may enhance the clinical feasibility of transplanting allogeneic
      hepatocytes.

PMID- 11330548
TI  - Common iliac artery stenosis presenting as renal allograft dysfunction in two
      diabetic recipients.
AB  - BACKGROUND: Suprarenal common iliac artery stenosis is an uncommon but reversible
      cause of allograft dysfunction in renal transplant recipients. METHOD: We
      describe two diabetic renal transplant recipients with worsening hypertension,
      edema, and azotemia. Magnetic resonance angiography (MRA) demonstrated tight
      stenoses in the common iliac artery proximal to the allograft anastomosis site
      with patent renal transplant artery in both cases. These findings were later
      confirmed with carbon dioxide angiography. RESULTS: No acute rejection was noted
      on renal biopsy in either case. Placement of percutaneous iliac artery Wallstents
      resulted in decrease of serum creatinine from 6.5 to 2.0 mg/dl and 1.7 to 1.0
      mg/dl within 2 and 4 weeks, respectively. CONCLUSION: Common iliac artery
      stenosis should be suspected in renal transplant recipients presenting with
      worsening hypertension, edema and azotemia. MRA for screening followed by carbon
      dioxide angiography and placement of intravascular stents for focal vascular
      obstructive lesions reverses allograft dysfunction.

PMID- 11330549
TI  - Dobutamine stress echocardiography for orthotopic liver transplant evaluation.

PMID- 11330550
TI  - Liver transplantation in Polysplenia syndrome.

PMID- 11330551
TI  - Has hepatocyte growth factor mitogenic effect on islet cells in vivo?

PMID- 11330552
TI  - Why is the proportion of patients doing peritoneal dialysis declining in North
      America?

PMID- 11330554
TI  - The effect of advanced glycation end-products and aminoguanidine on TNFalpha
      production by rat peritoneal macrophages.
AB  - OBJECTIVE: To evaluate the effect of advanced glycation end-products (AGEs) and
      the inhibitor of their formation, aminoguanidine, on tumor necrosis factor-alpha
      (TNFalpha) production (as a functional marker) by rat peritoneal macrophages
      (PMphi). DESIGN: Charles River rats underwent a daily intraperitoneal injection
      of peritoneal dialysis solution [(PDS), 4.25 g/dL dextrose; Dialine, Travenol,
      Ashdod, Israel] for a 2-month period (group E). Another group of rats was
      subjected to the same protocol with the addition of 25 mg/kg aminoguanidine
      (group A). Three control groups were utilized: (1) rats that were injected daily
      with aminoguanidine only (group AO), (2) rats that were injected with Dulbecco's
      phosphate-buffered saline (group D), and (3) rats in which no intervention was
      carried out (group C). After 2 months, PMphi were isolated from rat peritoneal
      effluent and their TNFalpha production measured by ELISA in cell-free culture
      supernatants, in both the basal state and after 24-hour stimulation with
      lipopolysaccharide (LPS). The concentrations of AGEs in peritoneal effluent were
      assayed and correlated to TNFalpha levels. PMphi obtained from normal rats were
      then incubated for 24 hours with (1) the peritoneal effluent of each of the above
      respective groups, with or without LPS; (2) increasing concentrations of AGEs (0
      250 microg/mL); and (3) increasing concentrations of aminoguanidine (0-7.5
      mg/mL), and TNFalpha secretion again determined. RESULTS: After 2 months of daily
      intraperitoneal injection of PDS, in the basal state, TNFalpha production was
      significantly higher in PMphi isolated from the peritoneal effluent groups
      (groups E, A, and AO) compared to controls (group C). Following LPS stimulation,
      a further increase in TNFalpha secretion was seen, with a significantly greater
      response in group AO versus groups E, A, and D. Effluent AGEs were markedly
      elevated only in group E. No correlation was found between TNFalpha secretion by
      these PMphi and the concentration of AGEs. On incubation with the respective
      peritoneal effluents (groups E, A, and AO), in both the basal and stimulated
      state, TNFalpha production by PMphi from normal rats was significantly enhanced
      compared to group C. Incubation with increasing concentrations of AGEs or
      aminoguanidine resulted in an increase of TNFalpha secretion by these PMphi.
      CONCLUSIONS: Following intermittent intraperitoneal administration of glucose
      based PDS, rat PMphi are chronically activated, as evidenced by increased basal
      TNFalpha secretion. The peritoneal effluent of such treated animals is capable of
      stimulating TNFalpha production by normal rat PMphi. These data suggest that
      glucose-based PDS acts as a primer of PMphi, which retain their ability to
      further stimulation by LPS. Although, in vitro, AGEs promote TNFalpha secretion
      by normal rat PMphi, in vivo, their influence is probably modulated by other
      factors. Aminoguanidine has a specific inducing effect on rat PMphi, independent
      of glucose-based PDS.

PMID- 11330553
TI  - Electrophysiology and glucose transport of human peritoneal mesothelial cells:
      implications for peritoneal dialysis.
AB  - OBJECTIVE: To elucidate ionic and glucose transport across human peritoneal
      mesothelium, we utilized an Ussing chamber setup and studied the
      electrophysiological characteristics and tissue permeabilities of human
      peritoneal mesothelial cells (HPMC) to L- and D-glucose. METHODS: Human
      mesothelial cells were grown on polyester filters (snapwell; Costar, Cambridge,
      MA, U.S.A.) that, upon confluence, were fitted into Ussing chambers.
      Transmesothelial resistance and resting potential were determined using
      electrophysiological techniques. Radiolabeled glucose was added to one side of
      the chamber and the permeabilities determined by serial sampling in the receptive
      compartment. RESULTS: The transmesothelial potential and resistance were 0.54 +/-
      0.07 mV (apical positive) and 20.4 +/- 3.2 ohms x cm2 respectively (mean +/- SEM,
      n = 36). The course of overall transfer of D- and L-glucose was examined using L
      glucose as a positive diffusion-plus-leak marker. The permeabilities of HPMC to D
      glucose were 3.00 +/- 0.26 cm/sec (apical-to-basolateral) and 3.25 +/- 0.27
      cm/sec (basolateral-to-apical) [n = 6 experiments, p = not significant (NS)],
      which were not different from those of L-glucose: 3.00 +/- 0.30 cm/sec (apical-to
      basolateral) and 2.71 +/- 0.24 (basolateral-to-apical) (n = 6 experiments, p =
      NS). CONCLUSIONS: The transepithelial resistance of HPMC is low and the ionic
      gradient, although it exists, is small and inconsequential. Passive paracellular
      flow accounts for the majority of transmesothelial glucose transport. The
      existence of a large paracellular shunt precludes the mesothelial membrane as a
      clinically relevant osmotic barrier.

PMID- 11330555
TI  - Intraperitoneal hyaluronan administration in conscious rats: absorption,
      metabolism, and effects on peritoneal fluid dynamics.
AB  - BACKGROUND: Hyaluronan (HA) is a major component of interstitial tissue that
      participates in fluid homeostasis, response to inflammation, and wound healing.
      Previous studies have shown that intraperitoneal administration of HA can affect
      peritoneal fluid transport during short peritoneal dialysis exchanges in
      anesthetized rats. We sought to investigate the effect of high molecular weight
      HA on peritoneal permeability in conscious rats during dialysis exchanges up to 8
      hours in duration. In addition, we sought to investigate the absorption of HA
      from the peritoneal cavity, its accumulation in peritoneal tissues, and its
      metabolism in normal and uremic rats. METHODS: Experiments were performed on male
      Wistar rats infused with 30 mL peritoneal dialysis solution (Dianeal, Baxter
      Healthcare; Castelbar, Ireland) containing 10 mg/dL HA or with Dianeal alone
      (control). Peritoneal fluid removal (net ultrafiltration), permeability to
      glucose, creatinine, and total proteins, and tissue and blood levels of HA were
      determined in separate groups of rats at 1,2, 4, 6, and 8 hours after
      intraperitoneal infusion. Hyaluronan appearance and disappearance from plasma
      were also studied for 24 hours in separate groups of normal and uremic rats.
      RESULTS: Net ultrafiltration was significantly greater (27%) in rats infused with
      HA at 4, 6, and 8 hours (p < 0.01) compared to controls. Transperitoneal
      equilibration of protein was reduced by 27% (p < 0.001) at 4 hours and by 30% (p
      < 0.01) at 8 hours. During the 8-hour exchange, peritoneal clearance of
      creatinine increased by 27% (p < 0.01), whereas the clearance of total protein
      decreased by 27% (p < 0.005). After 8 hours, 25.7% +/- 3.1% of the administered
      HA was absorbed from the peritoneal cavity, peritoneal tissue HA concentration
      was increased by 117% (p < 0.001), and plasma HA levels increased by 435% (p <
      0.001). Plasma HA levels returned to normal within 24 hours after intraperitoneal
      administration in both healthy and uremic rats. CONCLUSIONS: Hyaluronan added to
      dialysis fluid is absorbed from the peritoneal cavity and accumulates in
      peritoneal tissues. Hyaluronan supplementation produces changes in peritoneal
      permeability, leading to higher net ultrafiltration and peritoneal creatinine
      clearance, whereas total protein clearance decreases. The HA that is absorbed
      from the peritoneal cavity appears to be rapidly metabolized in both healthy and
      uremic rats.

PMID- 11330556
TI  - Hyaluronan preserves peritoneal membrane transport properties.
AB  - BACKGROUND: We have shown that intraperitoneal (i.p.) addition of hyaluronan (HA)
      in a single dwell study in rat could increase peritoneal fluid removal by
      decreasing the peritoneal fluid absorption rate. In this study, we investigated
      the impact of repeated use of HA on peritoneal membrane transport
      characteristics. METHODS: Twelve male Sprague-Dawley rats received a once-daily
      i.p. injection of 25 mL 4.25% glucose dialysis solution without (HP group, n = 6)
      or with 0.025% HA (HA group, n = 6) for 1 week. Forty-eight hours after the last
      injection, a 4-hour dwell using 25 mL 4.25% glucose dialysis solution with i.p.
      volume marker and frequent dialysate and blood samplings was performed in each
      rat as well as in rats that did not receive any injection (control group, n = 8).
      RESULTS: Although the i.p. volumes were significantly lower in the HP and HA
      groups compared to the control group, i.p. volume in the HA group was
      significantly higher than in the HP group. Net ultrafiltration at 4 hours was 5.6
      +/- 1.3 mL, 10.2 +/- 1.8 mL, and 13.2 +/- 0.6 mL for the HP, HA, and control
      group, respectively. The peritoneal fluid absorption rate decreased by 45% in the
      HA group compared to the HP group. There was no significant difference in
      peritoneal fluid absorption rate between the HA and the control group. No
      difference was found in the direct lymphatic absorption rate between the HP and
      HA groups [0.010 +/- 0.003 mL/minute in the HP group and 0.011 +/- 0.004 mL/min
      in the HA group] although they were both higher than that of the control group
      (0.004 +/- 0.001 mL/min). The solute transport rates were in general
      significantly higher in the HP group compared to the HA and control groups, and
      there was no significant difference between the latter two groups, except that
      protein transport rate was significantly lower in the HA group compared to the
      control group. CONCLUSIONS: The present study suggests that (1) repeated exposure
      to hypertonic glucose-based dialysis solution results in increased peritoneal
      solute transport rates, as well as increased peritoneal fluid absorption rates;
      and (2) these changes, reflecting a highly permeable peritoneal membrane, were
      ameliorated by repeated i.p. addition of hyaluronan. The similar changes in the
      direct lymphatic absorption rate in rats that received daily i.p. injection of
      dialysis solution suggest that direct peritoneal lymphatic absorption was not
      influenced by hyaluronan.

PMID- 11330557
TI  - Systemic lupus erythematosus and peritoneal dialysis: outcomes and infectious
      complications.
AB  - OBJECTIVE: Systemic lupus erythematosus (SLE) is the most common secondary
      glomerulonephritis resulting in end-stage renal disease (ESRD) among young adults
      in Taiwan. Studies of the infectious complications and outcomes among such SLE
      patients undergoing peritoneal dialysis (PD) are limited. DESIGN: A retrospective
      age- and gender-matched case control study. SETTING: A university teaching
      hospital. PATIENTS: There were 23 SLE patients with ESRD receiving PD for more
      than 3 months during the past 15 years. Another 46 age- and gender-matched non
      SLE nondiabetic patients receiving PD were selected as the control group in this
      study. INTERVENTION: All patients underwent PD as renal replacement therapy and
      were regularly followed up at this hospital. MAIN OUTCOME MEASURES: Technique
      survival and incidences of exit-site infection (ESI) and peritonitis in these
      patients. RESULTS: The SLE patients had a lower predialysis serum albumin than
      the control group (3.16 +/- 0.50 g/dL vs 3.52 +/- 0.50 g/dL, p < 0.01). The
      incidences of exit-site infection (ESI) and peritonitis were higher for SLE
      patients than for control patients (p < 0.01 and p < 0.001, respectively). Kaplan
      Meier survival analysis indicated that SLE patients had shorter time intervals to
      first infectious complications, and poorer technique survival. Infection was the
      major cause of dropout and mortality in the SLE patients. The SLE patients had a
      reduced chance of receiving a renal transplant. The use of steroids by SLE
      patients was associated with a higher incidence of peritonitis (p = 0.04), but
      association with ESI was insignificant. In a Cox regression model, the underlying
      SLE was the only risk factor for technique failure and time interval to first
      infectious complication. CONCLUSION: SLE patients undergoing PD are more
      susceptible to infection than age- and gender-matched non-SLE nondiabetic
      patients and have poorer technique survival. Systemic lupus erythematosus itself
      may further compromise the immunity of uremic patients.

PMID- 11330558
TI  - Long-term CAPD survival and analysis of mortality risk factors: 12-year
      experience of a single Mexican center.
AB  - OBJECTIVE: To evaluate patient and technique survival, and to analyze mortality
      risk factors in a large Mexican single-center continuous ambulatory peritoneal
      dialysis (CAPD) program. DESIGN: Cohort study. SETTING: Tertiary care, teaching
      hospital located in Mexico City. PATIENTS: All patients from our CAPD program
      (1985-1997) were retrospectively studied. INTERVENTIONS: Clinical and biochemical
      variables at the start of dialysis were recorded and considered in the analysis
      of risk factors. MAIN OUTCOME MEASURES: End points were patient (alive, dead, or
      lost to follow-up) and technique status at the end of the study (December 1997).
      RESULTS: 627 patients, 37% with diabetes mellitus (DM), were included. Median
      patient survival (+/- SE) was 5.1 +/- 0.6 years. In the univariate analysis, the
      following variables were associated (p < 0.05) with mortality: DM, old age,
      hypoalbuminemia, low serum creatinine, low serum phosphate, and lymphopenia. In
      the multivariate analysis, the only significant mortality risk factors were DM
      (RR 2.56, p < 0.0001), old age (RR 1.01, p = 0.01), hypoalbuminemia (RR 0.77, p =
      0.04), and lymphopenia (RR 0.98, p = 0.05). Median technique survival was 4.0 +/-
      0.2 years. Peritonitis, hypoalbuminemia, lymphopenia, old age, and DM were all
      significantly associated (p < 0.05) with technique failure in the univariate
      analysis, while in the multivariate analysis, only DM (RR 1.78, p = 0.001),
      peritonitis (RR 1.13, p = 0.004), lymphopenia (0.98, p = 0.04), and
      hypoalbuminemia (RR 0.80, p = 0.06) were technique failure predictors.
      CONCLUSIONS: Patient survival in our setting is similar to that reported in other
      series. Diabetes mellitus, lymphopenia, and hypoalbuminemia were the strongest
      predictive factors for mortality and technique failure on CAPD. Our 12-year CAPD
      program is one of the largest single-centers reported in CAPD literature.

PMID- 11330559
TI  - Diagnostic value of effluent endotoxin level in gram-negative peritonitis in CAPD
      patients.
AB  - OBJECTIVE: To evaluate the diagnostic usefulness of effluent endotoxin by Limulus
      amoebocyte lysate (LAL) assay in gram-negative peritonitis patients on continuous
      ambulatory peritoneal dialysis (CAPD) therapy. DESIGN: Prospective study with
      patients serving as their own controls. Standard microbiologic work up and
      endotoxin analysis of effluents (night dwell) were done during the pre- and
      posttreatment phases. SETTING: Specimens from three teaching hospitals were
      processed and tested at a common center. Patients were left for treatment at
      their respective centers without intervention. PATIENTS: 32 clinical peritonitis
      and 40 infection-free CAPD patients were studied. RESULTS: 75% (n = 24) of
      cultures were positive: 41.6% (n = 10) gram-negative and 58.4% (n = 14) gram
      positive bacteria. Effluents of pre- and posttreated gram-negative cultures had
      endotoxin levels of 1.53 +/- 0.169 and 0.214 +/- 0.085 endotoxin units (EU)/mL,
      respectively (p < 0.0001); pre- and posttreated gram-positive levels of 0.102 +/-
      0.06 and 0.122 +/- 0.052 EU/mL, respectively (p > 0.05); pre- and posttreated
      culture-negative peritonitis levels of 0.110 +/- 6.025 and 0.087 +/- 0.031 EU/mL,
      respectively (p > 0.05); peritonitis-free effluents contained 0.117 +/- 0.079
      EU/mL. The diagnostic specificity and the sensitivity of LAL assay were 100% and
      98.2% respectively. CONCLUSION: Where initial microbiological work-up cannot
      demonstrate a pathogen, effluent endotoxin determined by quantitative LAL assay
      is a useful marker for diagnosis and management, within safe time limits, of gram
      negative peritonitis in CAPD patients.

PMID- 11330561
TI  - Acute effects of peritoneal dialysis on hemodynamics.
AB  - OBJECTIVES: To investigate the acute hemodynamic effects of peritoneal dialysis
      (PD) using the noninvasive Portapres technique [TNO Biomedical Instrumentation
      (TNO BMI); Amsterdam, The Netherlands]. DESIGN AND METHODS: Blood pressure was
      measured in 21 consecutive patients on continuous ambulatory PD during a standard
      peritoneal permeability analysis (SPA). Blood pressure, stroke volume, cardiac
      output, and total peripheral resistance were recorded and calculated using
      continuous finger pressure recordings with Portapres and Modelflow software (TNO
      BMI). The SPA consists of four phases: (1) drainage of night dwell dialysate, (2)
      instillation of a rinsing solution (1.36% glucose), (3) drainage of rinsing
      solution, and (4) instillation of the test solution (3.86% glucose to which
      dextran 70 has been added). RESULTS: Both systolic blood pressure (SBP) (7 +/- 9
      mmHg, p < 0.005) and diastolic blood pressure (DBP) (5 +/- 6 mmHg, p < 0.01)
      increased during phase 2. Systolic BP and DBP increased further during phase 4
      (SBP 8 +/- 14 mmHg, p < 0.05; DBP 6 +/- 8 mmHg, p < 0.005). These BP increases
      were caused by a rise in total peripheral resistance of 10% +/- 18% (p< 0.05)
      during phase 1, and 15% +/- 21% (p < 0.005) during phase 2. CONCLUSIONS:
      Instillation and dwell of a dialysis solution during PD causes a rise in blood
      pressure. This is caused by an increase in total peripheral resistance. Factors
      influencing total peripheral resistance could be a direct mechanical effect of
      dialysate on mesenteric resistance vessels or a temperature-related effect.

PMID- 11330560
TI  - Comparison of hemostatic disturbances between patients on CAPD and patients on
      hemodialysis.
AB  - OBJECTIVE: Disturbances in hemostasis are common findings in uremic patients.
      Both bleeding diathesis and thrombosis are observed. The purpose of this study
      was to assess whether renal replacement therapy in the form of hemodialysis (HD)
      or continuous ambulatory peritoneal dialysis (CAPD) affects coagulation and
      fibrinolysis in patients with end-stage renal failure. DESIGN: Comparison of
      hemostatic measures in patients on CAPD, HD, and matched healthy controls.
      SETTING: Department of Nephrology and Internal Medicine, Bialystok University
      School of Medicine. PATIENTS AND METHODS: Twenty-four HD patients and 23 CAPD
      patients were evaluated with respect to platelet aggregation, hemostatic
      parameters, serum lipids, lipoprotein(a), and cytokines [tumor necrosis factor
      alpha (TNFalpha) and interleukin-1 (IL-1)]. INTERVENTIONS: Four exchanges of CAPD
      per day, using 2.0 L dialysate over a period of 25 +/- 31 months; or 4-5 hours of
      HD 3 times per week for a period of 31 +/- 22 months. RESULTS: Platelet
      aggregation in whole blood and platelet-rich plasma was significantly impaired in
      both groups of dialyzed patients compared to healthy volunteers. Markers of
      endothelial cell injury (thrombomodulin and von Willebrand factor) were
      significantly higher in HD and CAPD patients compared to the control group. A
      similar pattern of changes was observed for lipoprotein(a), fibrinogen, tissue
      factor pathway activity, and factor VII activity. Activity of factor X was
      significantly enhanced in CAPD compared to HD patients and controls. Euglobulin
      clot lysis time was significantly prolonged in HD and CAPD patients over
      controls, being more prolonged in CAPD patients. Markers of ongoing coagulation
      (thrombin-antithrombin complexes and prothrombin fragments 1+2) were higher in
      uremic patients, significantly higher in CAPD than in HD. A marker of ongoing
      fibrinolysis (plasmin-antiplasmin complexes) was higher in uremic patients but
      was lower in CAPD than in HD patients. Concentrations of TNFalpha and IL-1 were
      higher in HD than in CAPD patients. CONCLUSION: Patients on CAPD showed evidence
      of a higher degree of hypercoagulation than HD patients.Thus, hemostatic
      abnormalities in end-stage renal failure may be affected to some extent by the
      choice of renal replacement therapy.

PMID- 11330562
TI  - Prevalence of malnutrition assessed by bioimpedance analysis and anthropometry in
      children on peritoneal dialysis.
AB  - OBJECTIVE: To evaluate the sensitivity of anthropometry and bioelectrical
      impedance analysis (BIA) in detecting alterations in body composition of children
      treated with peritoneal dialysis (PD), and to determine the prevalence of
      malnutrition in this population, in short- and long-term PD duration, using
      anthropometric and BIA-derived indices. PATIENTS: Eighteen children treated with
      automated PD (11 males, 7 females; mean age 8.7 +/- 4.7 years). DESIGN: Eighteen
      patients were studied using anthropometry and BIA at the start (t0) and after 6
      months (t1) of PD, 15 of these patients at 12 months (t2), and 8 at 24 months
      (t3) of PD. Midarm muscle circumference (MAMC), arm muscle area (AMA), and arm
      fat area (AFA) were calculated from anthropometric measures according to
      Frisancho (FrisanchoAR. New norms of upper limb fat and muscle areas for
      assessment of nutritional status. Am J Clin Nutr 1981; 34:2540-5.). The
      bioelectrical measures of resistance (R) and reactance (Xc) were obtained
      directly from the impedance signal; phase angle (PA) and distance (D) were
      calculated using mathematical formulas. Nutritional status was assessed by
      anthropometric measurements and BIA-derived indices, expressed as standard
      deviation scores (SDS), and by a score system based on BIA and anthropometric
      parameters. The percentage of children with values of anthropometric and BIA
      derived indices below the 3rd percentile or between the 3rd and 25th percentiles,
      and the percentage of children with scores of 7-12 and 4-6 were calculated in
      order to detect patients with severe or moderate derangement of nutritional
      status. RESULTS: The mean SDS values of Xc, PA, and D significantly improved (p =
      0.05, p = 0.001, p = 0.02) during the first 6 months of PD and remained almost
      stable during the following months. The SDS values of the anthropometric indices
      were less compromised than those of the BIA-derived indices, particularly at the
      start of dialysis. By 6 months, the percentages of children with values of BIA
      and anthropometric indices below the 3rd percentile had decreased. The
      percentages of patients with moderate and severe derangement of BIA and
      anthropometric indices remained substantially unchanged after 12 months. However,
      at 24 months, the percentage of patients with moderate derangement of BIA indices
      increased. All these findings were confirmed by the nutritional score system.
      CONCLUSION: BIA is more sensitive than anthropometry in detecting alterations in
      body composition of children on PD. The prevalence of malnutrition, high at the
      commencement of PD, decreases during the first year of treatment but not over the
      long term.

PMID- 11330563
TI  - Changes in peritoneal equilibration test values during long-term peritoneal
      dialysis in peritonitis-free children.
AB  - Little is known about the changes in peritoneal equilibration test (PET) values
      in children on long-term peritoneal dialysis (PD). In the present study, a PET
      was carried out every 6 months in 39 children (mean age 8.8 +/- 5.5 years)
      undergoing PD for 6 to 85 months (mean 36.9 +/- 23.1 months). Patients
      experiencing peritonitis were excluded. Both D/P creatinine (dialysate-to-plasma
      ratio of creatinine at 4 hours) and D/D0 glucose (ratio of dialysate glucose at 4
      hours' dwell time to dialysis glucose at 0 dwell time) were measured 195 times in
      this series of patients. No remarkable change was found for D/P creatinine or
      D/D0 glucose during the first 24 months of PD but thereafter, D/P creatinine
      increased gradually and D/D0 glucose decreased gradually. Mean D/P creatinine
      increased significantly after the first 24 months of PD: from 0.66 +/- 0.12
      during the first 24 months, to 0.70 +/- 0.09 after 25 months and more of PD (p =
      0.0051). Mean D/D0 glucose decreased significantly after 24 months of PD: from
      0.42 +/- 0.09 during the first 24 months, to 0.38 +/- 0.08 after 25 months and
      more of PD (p = 0.0015). The most significant change for both D/P creatinine and
      D/D0 glucose occurred after 24 months of PD. It seems reasonable to consider the
      mean PET values at 24 months of PD as the standard PET values.

PMID- 11330564
TI  - QT dispersion and signal-averaged electrocardiogram in hemodialysis and CAPD
      patients.
AB  - OBJECTIVE: The aim of this study was to compare QT dispersion (QTd) and signal
      averaged electrocardiogram (SA-ECG) parameters that may predict risk of malignant
      arrhythmias in patients on hemodialysis (HD), on continuous ambulatory peritoneal
      dialysis (CAPD), and in controls. SETTING: Controlled cross-sectional study in a
      tertiary-care setting. PATIENTS: 28 HD (M/F 18/10; mean age 32 +/- 9 years), 29
      CAPD (M/F 17/12; mean age 34 +/- 10 years), and 29 healthy controls (M/F 17/12;
      mean age 32 +/- 8 years) were included. INTERVENTIONS: On ECG, minimum (QTmin)
      and maximum (QTmax) QT duration and their difference (QTd) were measured. In SA
      ECG, duration of filtered QRS, HFLA signals less than 40 microV, and RMS voltage
      (40 ms) were also measured. RESULTS: Higher serum Ca2+ and lower K+ levels were
      found in CAPD compared to HD. All QT parameters were increased in HD and CAPD
      compared to controls. QT dispersion was significantly prolonged in HD compared to
      CAPD. In HD, QTd was correlated with left ventricular (LV) mass index (r = 0.53,
      p = 0.004), but not in CAPD (r = -0.09, p = 0.63). QT dispersion was
      significantly prolonged in patients with LV hypertrophy compared to patients
      without hypertrophy on HD (68 +/- 18 ms vs 49 +/- 18 ms, p = 0.008). In the
      analysis of SA-ECG, 3 of the 28 (11%) HD and 2 of the 29 (7%) CAPD patients had
      abnormal late potentials. Patients on HD and CAPD had significantly higher
      filtered-QRS duration compared to controls (105 +/- 15 ms and 104 +/- 12 ms vs 95
      +/- 5 ms, respectively, p = 0.04). Patients with LV hypertrophy had higher
      filtered-QRS duration compared to patients without hypertrophy (109 +/- 12 ms vs
      95 +/- 8 ms, p < 0.001). CONCLUSION: Dialysis patients had prolonged QTd and
      increased filtered-QRS duration in SA-ECG compared to controls. Patients on HD
      had longer QTd than patients on CAPD. QTd has been correlated to LV mass index in
      HD, but not in CAPD. This difference might be due to the effect of different
      dialysis modalities on electrolytes, especially the higher serum Ca2+ levels.

PMID- 11330565
TI  - Fluoroscopic manipulation is also useful for malfunctioning swan-neck peritoneal
      catheters.

PMID- 11330566
TI  - Long-term effectiveness of intraperitoneal erythropoietin in children on NIPD by
      administration in small bags.

PMID- 11330567
TI  - Peritonitis following surgical procedures in peritoneal dialysis.

PMID- 11330568
TI  - Oral ciprofloxacin is ineffective in culture-negative peritonitis.

PMID- 11330569
TI  - Glucose degradation products and peritoneal membrane function.
AB  - BACKGROUND: The bioincompatibility of peritoneal dialysis fluids (PDF) in current
      use has been partially attributed to the presence of glucose degradation products
      (GDPs), which are generated during heat sterilization of PDF. Several of the GDPs
      have been identified and we have recently demonstrated that these GDPs per se may
      impair the viability and function of human peritoneal mesothelial cells (HPMC) in
      vitro. It is also possible that GDP-related toxicity is further exacerbated by
      the milieu of PDF. We review the current literature on GDP and present the
      results of experiments comparing the impact of heat- and filter-sterilized PDF on
      the viability and function of HPMC. METHODS: Peritoneal dialysis fluids with low
      (1.5%) and high (4.25%) glucose concentrations were laboratory prepared according
      to the standard formula and sterilized either by heat (H-PDF; 121 degrees C, 0.2
      MPa, 20 minutes) or filtration (F-PDF; 0.2 microns). The buildup of GDP was
      confirmed by UV absorbance at 284 nm. Confluent HPMC monolayers were exposed to
      these solutions mixed 1:1 with standard M199 culture medium. After 24 hours, cell
      viability was assessed with the MTT assay, and interleukin-1beta-stimulated
      monocyte chemotactic protein-1 (MCP-1) release with specific immunoassay.
      RESULTS: Exposure of HPMC to H-PDF resulted in a significant decrease in cell
      viability, with solutions containing 4.25% glucose being more toxic than 1.5%
      glucose-based PDF (27.4% +/- 3.4% and 53.4% +/- 11.0% of control values,
      respectively). In contrast, viability of HPMC exposed to F-PDF was not different
      from that of control cells. Moreover, treatment with H-PDF impaired the release
      of MCP-1 from HPMC to a significantly greater degree compared to F-PDF (17.4% and
      24.9% difference for low and high glucose PDF, respectively). CONCLUSIONS:
      Exposure of HPMC to H-PDF significantly impairs cell viability and the capacity
      for generating MCP-1 compared to F-PDF. This effect is likely to be mediated by
      GDPs present in H-PDF but not in F-PDF.

PMID- 11330570
TI  - Importance of blood pressure and volume control in peritoneal dialysis patients.
AB  - OBJECTIVES: To review the factors that impact control of blood pressure and
      euvolemia in peritoneal dialysis patients. DESIGN: Review of the most recent
      publications on this subject; inclusion of some personal data on the relation
      between plasma volume and evolution of blood pressure in short-term and long-term
      peritoneal dialysis patients. SETTING: Peritoneal dialysis program in a
      university hospital. RESULTS: The literature on circadian blood pressure and the
      role of the decreased compliance of the great vessels in uremia is reviewed.
      Analysis of the long-term evolution of plasma volume in peritoneal dialysis
      patients in correlation with the evolution of blood pressure indicates a positive
      correlation in 36 of 46 simultaneous determinations. The treatment of volume
      overload and hypertension in peritoneal dialysis includes the prescription of
      loop diuretics, preservation of residual renal function, reduction of dietary
      salt intake, and prevention and treatment of peritoneal ultrafiltration failure.
      CONCLUSIONS: A reduction in the great cardiovascular mortality in peritoneal
      dialysis patients as nowadays observed can only be expected when more attention
      is paid to better control of hypervolemia and hypertension in these patients.

PMID- 11330571
TI  - Aquaporins: roles in renal function and peritoneal dialysis.
AB  - Aquaporin (AQP) water channels are important in the function of the kidney.
      Constitutively expressed AQP1 in the proximal tubule and descending limb is
      important in normal fluid absorption and in the counter-current multiplication
      system. The vasopressin-regulated shuttling of AQP2 is essential in antidiuresis
      and the regulation of water balance. Genetic damage to AQPs, or pathological
      changes in expression or function, impair renal water handling. The most striking
      examples of this involve disruption of AQP2 function, which can result in
      profound nephrogenic diabetes insipidus. Aquaporin 1 is present in capillaries
      and venules and appears to be important in peritoneal dialysis, where it appears
      to represent the "ultrasmall pores" of the three-pore model. Decreased expression
      or function of AQP1 may be responsible for some cases of ultrafiltration failure,
      but further evidence will be required to establish whether this is the case.

PMID- 11330572
TI  - Does enalapril prevent peritoneal fibrosis induced by hypertonic (3.86%)
      peritoneal dialysis solution?
AB  - OBJECTIVE: Peritoneal fibrosis (PF) is one of the most serious causes of failure
      in continuous ambulatory peritoneal dialysis (PD). Although the underlying
      mechanism responsible for the genesis of PF is still unknown, transforming growth
      factor beta (TGFbeta1) has been shown to be associated with PF. Angiotensin
      converting enzyme inhibitors have been shown to prevent the stimulating effect of
      growth factors. The aim of the present study was to investigate the effect of
      enalapril on peritoneal function and morphology in a rat model of experimental
      PF. METHODS: Twenty-one albino Wistar rats were divided into three groups: (1)
      the control group (C) received 10 mL isotonic saline intraperitoneally (i.p.),
      (2) the dextrose (Dx) group 10 mL 3.86% dextrose PD solution i.p., and (3) the
      enalapril-treated group (ENA) 10 cc 3.86% dextrose PD solution i.p. plus 100 mg/L
      enalapril in drinking water. After 4 weeks, a 1-hour peritoneal equilibration
      test was performed with 20 mL 2.27% dextrose PD solution. Dialysate-to-plasma
      urea ratio (D/P urea), glucose reabsorption (D1/D0 glucose), ultrafiltration (UF)
      volume, and levels of dialysate protein, TGFbeta1, and cancer antigen 125 (CA125)
      were determined. The parietal peritoneum was evaluated histologically by light
      microscopy. RESULTS: Administration of enalapril resulted in preserved UF (-0.2
      +/- 0.7 mL vs 1.7 +/- 0.3 mL, p < 0.05), protein loss (2.3 +/- 0.5 g/L vs 1.6 +/-
      0.2 g/L, p > 0.05), and peritoneal thickness (77 +/- 7 microns vs 38 +/- 5
      microns, p < 0.001). D/P urea increased significantly in the Dx group (p< 0.05).
      Both higher levels of TGFbeta1 (undetectable vs 298 +/- 43 pg/mL, p < 0.001) and
      lower levels of CA125 in dialysate effluent (0.94 +/- 0.5 U/L vs 0.11 +/- 0.1
      U/L, p > 0.05) were determined in the Dx group. CONCLUSION: These findings show
      that peritoneal morphology and function tests were dramatically deranged in the
      Dx group. The same properties were partially preserved in the ENA group. The
      production of TGFbeta1 was significantly reduced but peritoneal thickness was not
      completely inhibited. In conclusion, by inhibiting the production of TGFbeta1,
      enalapril can preserve peritoneal histology, peritoneal function, and remodeling
      of mesothelial cells.

PMID- 11330573
TI  - Monitoring of long-term peritoneal membrane function.
AB  - OBJECTIVE: Peritoneal membrane function influences dialysis prescription and
      clinical outcome and may change with time on treatment. Increasingly
      sophisticated tools, ranging from the peritoneal equilibration test (PET) to the
      standard permeability analysis (SPA) and personal dialysis capacity (PDC) test,
      are available to the clinician and clinical researcher. These tests allow
      assessment of a number of aspects of membrane function, including solute
      transport rates, ultrafiltration capacity, effective reabsorption, transcellular
      water transport, and permeability to macromolecules. In considering which tests
      are of greatest value in monitoring long-term membrane function, two criteria
      were set: those that result in clinically relevant interpatient differences in
      achieved ultrafiltration or solute clearances, and those that change with time in
      treatment. STUDY SELECTION: Clinical validation studies of the PET, SPA, and PDC
      tests. Studies reporting membrane function using these methods in either long
      term (5 years) peritoneal dialysis patients or longitudinal observations (> 2
      years). DATA EXTRACTION: Directly from published data. Additional, previously
      unpublished analysis of data from the Stoke PD Study. RESULTS: Solute transport
      is the most important parameter. In addition to predicting patient and technique
      survival at baseline, there is strong evidence that it can increase with time on
      treatment. Whereas patients with initially high solute transport drop out early
      from treatment, those with low transport remain longer on treatment, although,
      over 5 years, a proportion develop increasing transport rates. Ultrafiltration
      capacity, while being a composite measure of membrane function, is a useful guide
      for the clinician. Using the PET (2.27% glucose), a net ultrafiltration capacity
      of < 200 mL is associated with a 50% chance of achieving less than 1 L daily
      ultrafiltration at the expense of 1.8 hypertonic (3.86%) exchanges in anuric
      patients. Using a SPA (3.86% glucose), a net ultrafiltration capacity of < 400 mL
      indicates ultrafiltration failure. While there is circumstantial evidence that,
      with time on peritoneal dialysis, loss of transcellular water transport might
      contribute to ultrafiltration failure, none of the current tests is able to
      demonstrate this unequivocally. Of the other membrane parameters, evidence that
      interpatient differences are clinically relevant (permeability to
      macromolecules), or that they change significantly with time on treatment
      (effective reabsorption), is lacking. CONCLUSION: A strong case can be made for
      the regular assessment by clinicians of solute transport and ultrafiltration
      capacity, a task made simple to achieve using any of the three tools available.

PMID- 11330574
TI  - Local recurrence after curative resection of cancer of the rectum without total
      mesorectal excision.
AB  - PURPOSE: The aim of this article was to examine local recurrence after curative
      resection for carcinoma of the rectum in which the surgical technique of total
      mesorectal excision was not performed. METHODS: A single surgeon managed the
      patients and the data collected prospectively. Total excision of the distal
      mesorectum was not performed in the upper third or mid rectum. RESULTS: From 1969
      to 1993 curative resections were performed in 549 patients, of which 17 died
      postoperatively, leaving 532 for analysis. Sphincter-saving resection was
      performed in 468 patients (88 percent) and abdominoperineal excision in 58 (10.9
      percent). The pathology stages (Dukes) were A, 158 (29.7 percent); B, 184 (34.7
      percent); and C, 190 (35.7 percent). Five hundred seventeen patients (97.2
      percent) were followed up for a minimum of five years. The median period of
      follow-up was 82 months. Local recurrence confined to the pelvis occurred in 17
      patients, and local recurrence associated with distant metastases occurred in 24
      patients. The total five-year local recurrence rate was 7.6 percent. Local
      recurrence was increased in Stage C tumors (P = <0.0001). Diathermy dissection in
      the pelvis was associated with a decreased local recurrence rate (P = 0.023). The
      five-year survival rate in curative resections was 72.5 percent. CONCLUSIONS: It
      is essential that articles presenting local recurrence rates should include both
      local recurrence in isolation and that which occurs with distant metastases.
      Although total mesorectal excision for rectal cancer was not performed in this
      study, the local recurrence rate is not materially different from that in several
      articles where total mesorectal excision has been used. Whether the distal
      mesorectum needs to be pursued in mid-rectal cancer is not yet proven.

PMID- 11330575
TI  - Long-term follow-up after ileoanal pouch procedure: algorithm for diagnosis,
      classification, and management of pouchitis.
AB  - PURPOSE: Inflammation of the ileoanal pouch (pouchitis) is one of the main
      complications after restorative proctocolectomy, yet its cause remains poorly
      understood. A standardized definition and diagnostic procedures in pouchitis are
      lacking. METHOD: We analyzed all cases of pouchitis occurring in a group of 308
      patients (210 with ulcerative colitis, 98 with familial adenomatous polyposis)
      who took part in a prospective long-term follow-up program. The severity of
      pouchitis was measured using a pouchitis activity score (Heidelberg Pouchitis
      Activity Score). An algorithm for the classification and management of pouchitis
      was established which enables the clinician: 1) to determine the severity of
      pouchitis, 2) to differentiate between primary pouchitis and pouchitis caused by
      surgical complications (secondary pouchitis), and 3) to evaluate the course
      (acute vs. chronic (> 3 months)). RESULTS: The median duration of follow-up was
      48 (range, 13-119) months. At least one episode of pouchitis was diagnosed in 29
      percent of patients with ulcerative colitis and in 2 percent of familial
      adenomatous polyposis patients. Secondary pouchitis occurred in 6 percent of
      ulcerative colitis patients and was cured by surgical treatment in 13 (87
      percent) of 15 cases. Primary pouchitis was diagnosed in 23 percent of ulcerative
      colitis patients, including 6 percent of all ulcerative colitis patients with
      chronic primary pouchitis. The latter showed poor response to medical treatment.
      In one case multifocal high-grade dysplasia occurred. Histologic examination of
      the excised pouch identified a carcinoma originating from the ileal mucosa.
      CONCLUSIONS: Ulcerative colitis patients after restorative proctocolectomy face a
      high risk of developing pouchitis. The algorithm used in this study was highly
      efficient in identifying patients with a secondary pouchitis who require surgical
      treatment and patients with chronic primary pouchitis. For the latter, long-term
      surveillance seems mandatory because of the risk of malignant transformation of
      the pouch mucosa.

PMID- 11330576
TI  - Computerized assessment of complications after colorectal surgery: is it valid?
AB  - PURPOSE: Historically, complication rates after colorectal surgery have been
      stratified by disease process, type of operation, or anesthesia risk derived
      after an intensive review of the medical record. Newer computer applications
      purport to shorten this process and predict the probability of postoperative
      complications by distinguishing them from comorbidities that are commingled on
      uniform discharge codes. We analyzed CaduCIS software, which uses discharge
      codes, to determine whether its predictions of comorbidity and complications were
      comparable to what was interpreted on the medical record. METHODS: Two-hundred
      seventy patients were analyzed according to the principal and secondary diagnoses
      coded on discharge. Coding inaccuracies of clinical occurrences were identified
      by physician review of each medical record. The actual incidences of 17 common
      preoperative comorbidities and 11 postoperative complications were compared with
      those predicted by CaduCIS. RESULTS: The CaduCIS-predicted distribution of
      comorbidities was similar to the actual occurrences in 15 of 17 categories. The
      overall incidence of complications obtained by physician (actual) review was 47
      percent, compared with 46 percent predicted by CaduCIS. However, there was a
      statistical difference between the CaduCIS-predicted and the actual complication
      rates in 5 of the 11 categories. The most common preoperative comorbidity and
      complication was cardiopulmonary (47 percent and 28 percent, respectively).
      CONCLUSION: The overall complication rate interpreted from the medical record (47
      percent) was accurately predicted by CaduCIS (46 percent). Predictions of 5 of 11
      individual complications were underestimated because of charting and coding
      inaccuracies, not because of computerized errors. Because uniform discharge
      coding of commingled comorbidity and complications is increasingly used to
      rapidly compute surgical outcomes, colon and rectal surgeons need to ensure
      compatibility of the actual and coded medical records.

PMID- 11330577
TI  - Outcome analysis of HIV-positive patients with anal squamous cell carcinoma.
AB  - PURPOSE: With improved antiretroviral therapy, HIV-positive patients are
      achieving a longer life expectancy. An increased incidence of anal squamous cell
      carcinomas has been noted in these patients. The purpose of this study was to
      determine the outcome of HIV-positive patients with anal squamous cell
      carcinomas. METHODS: We conducted a review based on our tumor registry from 1980
      through 1999. We identified 73 patients with anal squamous cell carcinoma treated
      at the University of Texas Southwestern Medical Center affiliated hospitals; 23
      were HIV positive (18 had AIDS). In the HIV-positive group, 9 had in situ
      squamous carcinomas and 14 had invasive squamous cell carcinomas. Data collected
      included age, CD4 count, treatment, complications, and survival; these data were
      analyzed by Student's t-test. RESULTS: All patients were male. Those with
      squamous cell cancer of the anus were offered radiation therapy and chemotherapy.
      Beginning in 1998, all patients received highly active antiretroviral therapy
      before treatment. Seven of 14 anal squamous cell carcinoma patients had their
      therapy adjusted owing to toxicity. Morbidity included proctocolitis and diarrhea
      (n = 2) requiring diversion (n = 1), hemorrhagic cystitis (n = 1), neutropenic
      fever (n = 3), bone marrow suppression (n = 1), and urethral stricture (n = 1).
      Mean age was 42 years for anal squamous cell carcinoma patients and 36 years for
      squamous cell carcinoma in situ patients (P = 0.05). Mean CD4 count was 222
      cells/ml in patients with infiltrating carcinoma and 200 in the in situ patients
      (P = NS). One-year and five-year mortality rates, respectively, were 40 percent
      and 80 percent for infiltrating carcinoma patients and 17 percent and 50 percent
      for the in situ patients. Both of the in situ patients who died had CD4 counts
      <20 cells/ml at diagnosis, whereas the rest had CD4 counts >100 cells/ml and are
      currently without anal disease. Mean CD4 count at diagnosis for all patients who
      died was 133 cells/ml, whereas for those surviving, it was 261 cells/ml (P =
      0.03). Eight (all with infiltrating carcinoma) of the 10 patients who died had
      persistent anal disease, but none had metastasis. CONCLUSION: HIV-positive
      patients with in situ carcinomas present at an earlier age than those with
      infiltrating lesions. In situ patients with CD4 counts as low as 105 cells/ml do
      well with local excision. A low CD4 count at diagnosis without highly active
      antiretroviral therapy predicts a poor prognosis. Because these patients appear
      to succumb to their HIV status and not the anal disease, anal squamous cell
      carcinoma should be included with cervical squamous cell carcinoma as an AIDS
      defining illness. HIV-positive patients, particularly AIDS patients, with
      invasive anal cancers and without effective antiretroviral therapy obtain little
      benefit and significant toxicity from current radiation therapy and chemotherapy.
      Initiation of highly active antiretroviral therapy in HIV-positive patients
      before radiation therapy and chemotherapy are begun may decrease toxicity and
      improve survival. Additional clinical trials are warranted to test this theory.

PMID- 11330578
TI  - Neoadjuvant therapy for adenocarcinoma of the rectum: tumor response and acute
      toxicity.
AB  - PURPOSE: This study was designed to evaluate the down-staging effect and acute
      toxicity of preoperative radiation and chemoradiation for primary adenocarcinoma
      of the rectum. METHODS: The results of pretreatment staging with transrectal
      ultrasound and computed tomography were compared with final histologic stage in
      260 consecutive patients who underwent neoadjuvant therapy and proctectomy for
      primary adenocarcinoma of the rectum. Patients underwent short-course radiation
      (2,000 cGy in five fractions), long-course radiation (4,500 cGy in 25 fractions),
      or chemoradiation (4,500 cGy in 25 fractions with concurrent chemotherapy).
      RESULTS: Down-staging of one or more T stages occurred in 116 of 260 (45 percent)
      patients overall (short-course radiation 34/82 (42 percent), long-course
      radiation 55/122 (45 percent), chemoradiation 27/56 (48 percent), P = not
      significant). Down-staging of one or more N stages occurred in 85 of 178 (48
      percent) patients overall (short-course radiation 12/45 (27 percent), long-course
      radiation 49/86 (57 percent), chemoradiation 24/47 (51 percent), P = 0.003).
      Complete pathologic response was observed in 16 of 260 (6 percent) patients
      overall (short-course radiation 4/82 (5 percent), long-course radiation 5/122 (4
      percent), chemoradiation 7/56 (13 percent), P = 0.08). Resection with negative
      margins (distal, proximal, and radial) was achieved in 211 of 227 patients (93
      percent) in whom complete radial margin data were available. Permanent stomas
      were created in 35 percent of patients; temporary stomas were created in 15
      percent. Thirty-three Grade 3 or 4 toxicities occurred in 22 of 260 (8 percent)
      patients overall during neoadjuvant therapy. Toxicity was more frequent in
      patients receiving chemoradiation (14/56; 25 percent) and long-course radiation
      (8/122; 7 percent) than in those receiving short-course radiation (0/82; 0
      percent), P < 0.0001. Perioperative complications occurred in 93 patients overall
      (36 percent). The postoperative mortality rate was 0.4 percent (1/260). There was
      no significant difference in the complication rate between patients treated with
      short-course radiation (26/82; 32 percent), long-course radiation (46/122; 36
      percent), and chemoradiation (21/56; 38 percent). CONCLUSION: Neoadjuvant therapy
      for adenocarcinoma of the rectum is well tolerated and can produce substantial
      down-staging and a high curative resection rate. Chemoradiation can achieve high
      complete pathologic response rates, although toxicity during neoadjuvant therapy
      is greater than for radiation alone. Short-course radiation can achieve down
      staging of both T stage and N stage.

PMID- 11330579
TI  - Molecular markers are predictors of recurrence and survival in patients with
      Dukes B and Dukes C colorectal adenocarcinoma.
AB  - PURPOSE: The goal was to investigate the prognostic value of various molecular
      markers like CEA, Cyclin D1, Bcl-2, c-Myc, p53, p21ras, Ki-67, CD44, Factor VIII
      related antigen, cytokeratin-19, adenoma antigen, and prolactin in patients with
      Dukes B and Dukes C colorectal adenocarcinoma. METHODS: These molecular markers
      were localized immunohistochemically in nonmalignant (n = 36) and malignant (n =
      98) diseases of the colorectum. Data were analyzed statistically using the SPSS
      software program. The patients with colorectal cancer were followed for a period
      of five years or their death within that period. RESULTS: The expression of
      carcinoembryonic antigen, Cyclin D1, Bcl-2, CD44, cytokeratin-19 and prolactin
      was significantly higher in malignant diseases (P < 0.05), whereas, p21ras was
      found to be significantly higher in nonmalignant diseases (P = 0.002) as compared
      with their respective counterparts. Besides Dukes stage, multivariate analysis
      indicated a significantly reduced relapse-free survival in patients expressing
      CD44 and cytokeratin-19 (P < 0.005). Similarly, besides Dukes stage, multivariate
      analysis indicated a significantly poor overall survival in patients expressing
      CD44, cytokeratin-19 and prolactin (P < 0.01). In patients with Dukes B disease,
      only cytokeratin-19 and CD44 expression attained statistical significance (P <
      0.05), whereas in patients with Dukes C disease, CD44, p21ras- and c-Myc
      expression attained statistical significance (P < 0.018). Also, a multivariate
      analysis in relation to treatment given was performed using CD44 and cytokeratin
      19. CONCLUSION: Besides Dukes stage, multivariate analysis of all the studied
      molecular markers showed that patients expressing CD44 and cytokeratin-19 had a
      significantly reduced relapse-free and poor overall survival. Moreover, patients
      expressing both these markers (CD44 and cytokeratin-19) had the lowest
      significant relative risk for developing recurrence than patients with both
      markers negative when treated with surgery followed by adjuvant chemotherapy as
      compared with patients treated with surgery alone. Thus, in patients with
      colorectal cancer, immunohistochemical localization of CD44 and cytokeratin-19
      may be included as a part of routine pathologic evaluation along with
      conventional prognostic factors.

PMID- 11330580
TI  - Expression of Ki-67 can assist in predicting recurrences of low-grade anal
      intraepithelial neoplasia in AIDS.
AB  - PURPOSE: The incidence of anogenital squamous-cell carcinoma was observed to have
      increased since the beginning of the human immunodeficiency virus infection
      epidemic among male homosexuals, both with acquired immunodeficiency syndrome and
      without acquired immunodeficiency syndrome. It seems that immunosuppression is
      the most important risk factor for the progression of anogenital lesions,
      recurrences of anal condyloma, and development of anal carcinoma, in particular
      in acquired immunodeficiency syndrome. High-grade anal intraepithelial neoplasia
      was predominantly observed in the human immunodeficiency virus-positive men. We
      have also observed a high rate of recurrences of anal lesions in cases of high
      grade anal intraepithelial neoplasia. However, there are many cases of
      recurrences of low-grade anal intraepithelial neoplasia that cannot be predicted
      by routine histologic studies. By using immunohistochemical methods, we studied
      the expression of Ki-67 in epithelial cells of low-grade anal intraepithelial
      neoplasia of patients with acquired immunodeficiency syndrome to try to predict
      recurrence of these lesions. METHODS: Anal biopsies of 38 patients were studied
      retrospectively. Of these patients, 14 had no recurrences (Group 1), and 24
      patients had recurrence of the anal lesions before one year of follow-up (Group
      2). RESULTS: The median percentage of Ki-67-positive cells in Group 1 was 6.3 +/-
      7.03 and in Group 2 was 24.1 +/- 16.72. The difference between Groups 1 and 2 was
      statistically significant (P < 0.001). CONCLUSIONS: Our results showed a high
      correlation between the percentage of Ki-67-positive cells and recurrences. We
      concluded that Ki-67 counting in low-grade anal intraepithelial neoplasia can aid
      in predicting recurrences and therefore aid in the follow-up of these patients.

PMID- 11330581
TI  - Preoperative assessment of vascularity by color Doppler ultrasonography in human
      rectal carcinoma.
AB  - PURPOSE: Although angiogenesis assessed by immunostaining endothelial cells
      (microvessel density) is a well-known prognostic factor in a wide variety of
      human solid tumors, preoperative determination of microvessel density seems to be
      difficult in rectal carcinoma. Thus, we performed transanal color Doppler
      ultrasonography in 46 patients with rectal carcinoma to assess preoperative
      angiogenic status and compare it with microvessel density in surgical specimens.
      METHODS: Time-averaged maximal velocity, peak systolic velocity, number of
      vascular points, and vascular point index were conducted by color Doppler
      ultrasonography in 46 patients with rectal carcinoma. Number of vascular points
      was defined as the number of vessels with pulsation in the section of tumor.
      Vascular point index was defined as the average number of vascular points divided
      by the area assessed by color Doppler ultrasonography in the section of tumor.
      The profiles of number of vascular points were similar to those assessed by
      microangiography in five rectal carcinomas. RESULTS: Vascular point index
      significantly correlated with microvessel density (P < 0.0001). No significant
      correlation was found between microvessel density and time-averaged maximal
      velocity or peak systolic velocity. Vascular point index was also a better
      indicator of lymph node metastasis and venous invasion than microvessel density.
      In addition, 11 of 46 cases with postoperative hematogenous metastasis (23.9
      percent) were observed prospectively. Vascular point index may be a best
      predictor for hematogenous metastasis from rectal carcinoma compared with peak
      systolic velocity, time-averaged maximal velocity, and microvessel density by
      receiver operating characteristic analysis. CONCLUSION: These results suggest
      that preoperative quantification of angiogenesis using color Doppler
      ultrasonography will provide quick and useful information in the management of
      rectal carcinoma.

PMID- 11330582
TI  - Prognostic value of K-ras mutations and allelic imbalance on chromosome 18q in
      patients with resected colorectal cancer.
AB  - PURPOSE: We designed this study to assess the frequency of K-ras mutations in
      patients with resected colorectal tumors and their association with survival. A
      second objective was to analyze the prognostic value of different K-ras
      genotypes. In a subgroup of patients we also investigated the presence of allelic
      imbalance on chromosome 18q and its relationship to clinical outcome. METHODS:
      One hundred fourteen colorectal tumors resected between 1983 and 1986 were
      analyzed to detect K-ras point mutations at codons 12, 13, and 61 by polymerase
      chain reaction followed by allele specific oligonucleotide hybridization. A
      subgroup of 77 tumors was further screened to detect loss of heterozygosity on
      chromosome 18q using three polymorphic microsatellite markers (D18S67, D18S474
      and D18S58). RESULTS: K-ras mutations were detected in 29 percent (33/114) of
      patients. K-ras mutations correlated with age and preoperative carcinoembryonic
      antigen levels, and there was some indication that they may be linked to poor
      survival, especially in Stage II tumors, where a subgroup of patients with
      aspartic and serine mutations showed significantly reduced survival (P = 0.03)
      compared with K-ras-negative patients. 18q loss of heterozygosity was present in
      39 percent (25/63) of tumors. A multivariate analysis of Stage II tumors showed
      that 18q loss of heterozygosity was significantly associated with a worse
      prognosis (P = 0.006). A significant decrease in survival was identified in ten
      patients harboring both genetic alterations (K-i mutations and 18q loss of
      heterozygosity; P = 0.02). CONCLUSIONS: In colorectal tumors, K-ras mutations and
      18q loss of heterozygosity are two genetic markers which may identify patients
      with more aggressive behavior, mainly in Stage II tumors. These findings warrant
      further research, because they can be useful in customizing adjuvant
      chemotherapy.

PMID- 11330583
TI  - Harmonic Scalpel vs. electrocautery hemorrhoidectomy: a prospective evaluation.
AB  - INTRODUCTION: Management of posthemorrhoidectomy pain remains a very
      unsatisfactory clinical dilemma. Compared with electrocautery and laser, the
      Harmonic Scalpel causes minimal lateral thermal injury during tissue dissection.
      PURPOSE: The aim of the study was to establish whether decreased lateral thermal
      injury translated into diminished posthemorrhoidectomy pain. METHODS: A
      prospective randomized trial comparing Harmonic Scalpel hemorrhoidectomy and
      electrocautery was undertaken. Fifty consecutive patients were randomized into
      two groups: Harmonic Scalpels and electrocautery hemorrhoidectomy. The
      indications included Grade III internal hemorrhoids with external components or
      Grade IV disease. Patients with additional anorectal pathology (fissure or
      fistula) were excluded, as were patients with neurologic deficits, chronic pain
      syndrome, and those already taking narcotic analgesics. Pain was assessed using a
      visual analog scale preoperatively and on postoperative Days 1, 2, 7, 14, and 28.
      Twenty-four-hour narcotic usage (Hydrocodone, 10 mg) was recorded on
      postoperative Days 1, 2, 7, 14, and 28. A three-quadrant modified Ferguson
      hemorrhoidectomy was performed with each patient in the prone jackknife position.
      RESULTS: Pain in the Harmonic Scalpel hemorrhoidectomy group was significantly
      less than in electrocautery patients on each postoperative day studied. Analgesic
      requirements were also significantly less in the Harmonic Scalpel group on Days
      1, 2, 7, and 14. There was no correlation between postoperative pain and grade of
      hemorrhoid, status of the surgical incision (open vs. closed), or any other study
      variable. Fifty-five percent of Harmonic Scalpel patients returned to work within
      one week of surgery, compared with 23 percent of electrocautery patients.
      CONCLUSION: The study demonstrates significantly reduced postoperative pain after
      Harmonic Scalpel hemorrhoidectomy compared with electrocautery controls. The
      diminished postoperative pain in the Harmonic Scalpel group likely results from
      the avoidance of lateral thermal injury.

PMID- 11330584
TI  - The Altemeier repair: outpatient treatment of rectal prolapse.
AB  - PURPOSE: Rectal prolapse typically occurs in elderly patients, who are often poor
      surgical candidates because of the presence of multiple comorbidities. Abdominal
      approaches to procidentia have low recurrence rates but are associated with
      higher rates of morbidity and mortality. Perineal rectosigmoidectomy (Altemeier
      repair) is a safe and effective approach to the treatment of rectal prolapse and
      can be done as an outpatient procedure. In this article, the results of a series
      of 63 consecutive Altemeier repairs are presented. METHODS: Between February 1993
      and December 1999, 63 patients (61 females) underwent Altemeier repair of rectal
      prolapse. The mean patient age was 79 years. Preoperative, intraoperative, and
      postoperative data were collected and analyzed for all patients. RESULTS: Median
      follow-up was 20.8 months. Seventy percent of patients were given a regional or
      local anesthetic. The average resected specimen length was 11.6 cm, and 83
      percent of anastomoses were stapled. Sixty-two percent of patients were
      discharged home on the day of surgery, and 80 percent were home within 24 hours.
      Complications occurred in 10 percent of patients, but there was no perioperative
      mortality. There was a 6.4 percent recurrence rate, and all recurrences were
      successfully treated with repeat Altemeier repair. All 63 patients had complete
      objective resolution of prolapse, and 87 percent had subjective improvement after
      repair. CONCLUSIONS: Altemeier repair of rectal prolapse is safe, produces
      minimal discomfort, and does not require a general anesthetic. It is ideally
      suited to be done on an outpatient basis, as was done in the majority of patients
      in our series. The recurrence rate is slightly higher than with abdominal
      resections, but morbidity and cost are lower, and repeat perineal resections are
      easily and safely performed.

PMID- 11330585
TI  - A comparison between dynamic pelvic magnetic resonance imaging and
      videoproctography in patients with constipation.
AB  - PURPOSE: This study attempts to compare the diagnostic efficacy of dynamic pelvic
      magnetic resonance imaging with that of videoproctography for the presence of
      rectocele, sigmoidocele, and intussusception as well as the measurement of
      anorectal angle and perineal descent in constipated patients. METHODS: Patients
      volunteering for the study and fulfilling the criteria for videoproctography to
      evaluate constipation were also scheduled for dynamic pelvic magnetic resonance
      imaging. Patients undergoing videoproctography were placed in the left lateral
      decubitus position, after which 50 ml of liquid barium paste was introduced into
      the rectum. After this, approximately 100 ml of thick barium paste similar to
      stool in consistency was injected into the rectum, and the patient was instructed
      to defecate while video images were taken. For dynamic pelvic magnetic resonance
      imaging, air, to be used as contrast, was allowed to accumulate in the rectum via
      examination with the patient in the prone position. A capsule was taped to the
      perineal skin immediately posterior to the anal orifice for marking. Sagittal and
      axial T1 images were obtained through the pelvis at 8-mm intervals with dynamic
      breathhold sagittal images of the anorectal region obtained at rest and during
      strain and squeeze maneuvers. Total acquisition time per maneuver was
      approximately 19 seconds. The tests were performed by different examiners blinded
      to the result of the other evaluation. The investigations were independently
      interpreted, findings compared, and patients questioned regarding their
      impression of dynamic pelvic magnetic resonance imaging and videoproctography.
      RESULTS: From June 1996 to April 1997, 22 patients (15 females) with a mean age
      of 68 (range, 21-85) years underwent both videoproctography and dynamic pelvic
      magnetic resonance imaging. Dynamic pelvic magnetic resonance imaging was only
      able to detect 1 of 12 (8.3 percent) anterior rectoceles and one of two (50
      percent) posterior rectoceles identified by videoproctography. It failed to
      recognize any of the rectoanal intussusception (zero of four) but did show 9 of
      12 (75 percent) sigmoidoceles. Significant discrepancy of measurement of the
      anorectal angle and perineal descent exists between the two studies, and dynamic
      pelvic magnetic resonance imaging was not able to detect any (0 of 11) of the
      patients with increased fixed perineal descent and only half (one of two) of the
      patients with increased dynamic perineal descent noted on videoproctography. All
      22 patients preferred dynamic pelvic magnetic resonance imaging over
      videoproctography because of greater comfort. CONCLUSION: Occasionally, the
      increased cost of new technology can be justified by the enhanced diagnostic
      yield. The ability to avoid unnecessary surgery or, conversely, to continue to
      search for otherwise occult pathology that can be surgically corrected justifies
      routine application of these new tools. However, this study has shown that,
      despite a cost of approximately ten times more for dynamic pelvic magnetic
      resonance imaging than for videoproctography, no clinical changes were made.
      Thus, on the basis of this study, we cannot endorse the routine application of
      dynamic pelvic magnetic resonance imaging for the evaluation of constipated
      patients. In certain selected individuals, it may play a role, but further study
      is necessary to clarify its exact role.

PMID- 11330586
TI  - Colectomy for slow-transit constipation: preoperative functional evaluation is
      important but not a guarantee for a successful outcome.
AB  - PURPOSE: This study was designed to assess the results of preoperative functional
      evaluation of patients with severe slow-transit constipation in relation to
      functional outcome. METHODS: Four hundred thirty-nine patients with chronic
      intractable constipation were evaluated by marker studies. Twenty-one patients
      underwent colectomy and ileorectal anastomosis for slow-transit constipation.
      Mean colorectal transit time was 156 hours (normal, <45 hours). Small-bowel
      transit time was normal in ten patients and delayed in five patients. Six were
      nonresponders. Morbidity was 33 percent. Small-bowel obstruction occurred in six
      patients; relaparotomy was done in four patients. Follow-up varied from 14 to 153
      (mean, 62) months. RESULTS: After three months, defecation frequency was
      increased in all. Mean stool frequency improved from one bowel movement per 5.9
      days to 2.8 times per day. Sixteen patients felt improved after surgery.
      Seventeen continued to experience abdominal pain, and 13 still used laxatives and
      enemas. Satisfaction rate was 76 percent (16 patients). After one year,
      defecation frequency was back at the preoperative level in five patients. An
      ileostomy was created in two more patients because of incontinence and persistent
      diarrhea. Eleven patients (52 percent) still felt improved. A relation between
      small-bowel function and functional results could not be demonstrated.
      CONCLUSIONS: Preoperative evaluation is important but not a guarantee for,
      successful outcome. Colectomy remains an ultimate option for patients with
      disabling slow-transit constipation, but patients should be informed that,
      despite an increased defecation frequency, abdominal symptoms might persist. Any
      promiscuous use of colectomy to treat constipation should be discouraged.

PMID- 11330587
TI  - Comparison of epineural or intramuscular nerve electrodes for stimulated
      graciloplasty.
AB  - OBJECTIVE: Two different techniques have been developed to stimulate the gracilis
      muscle when it is used in anal neosphincter reconstruction. These are direct
      neural stimulation and intramuscular electrode stimulation. The aim of this study
      was to compare these techniques. METHODS: Comparison was made of gracilis anal
      neosphincter reconstruction using neural stimulation (Royal London Hospital in
      the United Kingdom) with the intramuscular muscular method (University Hospital
      Maastricht in the Netherlands). The United Kingdom data were obtained from a
      retrospective database, whereas the Netherlands data were gathered prospectively.
      RESULTS: A successful outcome was achieved in 46 of 81 patients (57 percent) in
      London and 148 of 200 cases (74 percent) in the Maastricht study (chi-squared =
      7.2; P < 0.01). There was no significant difference between the two techniques in
      voltage required for stimulation of the neosphincter muscle during a ten-year
      period. Reoperative surgery for electrode failure or dislocation was required in
      21 (26 percent) patients in the London study, whereas only four (2.7 percent) of
      the Maastricht cases required such procedures (chi-squared = 37.8; P < 0.05). The
      high electrode plate failure rate in the London study was related to the source
      of manufacture. CONCLUSIONS: Both neural and intramuscular nerve techniques
      provide effective long-term stimulation of the gracilis anal neosphincter.

PMID- 11330588
TI  - Portal vein thrombosis successfully treated with a colectomy in active ulcerative
      colitis: report of a case.
AB  - Portal vein thrombosis is a rare complication in ulcerative colitis. We present a
      patient with portal vein thrombosis in ulcerative colitis who was successfully
      treated with colectomy. A 38-year-old Japanese female was admitted to our
      hospital because of an exacerbation of colitis. Abdominal ultrasonography
      performed because of liver dysfunction showed the thrombus in an umbilical
      portion of the portal vein. The patient underwent a subtotal colectomy and
      ileostomy because her colitis did not respond to intensive intravenous therapy.
      Although portal vein thrombus was treated with an intravenous infusion of
      urokinase before the operation, no change in the thrombus size was found.
      Approximately three months after the colectomy, the thrombus of the portal vein
      disappeared without anticoagulant therapy. Although a resection of an inflamed
      colon may be theoretically effective in the thrombosis in the inflammatory bowel
      disease, its benefit has not been confirmed. Our case suggests that the resection
      of the diseased bowel may have a favorable effect on the course of portal vein
      thrombosis in acute attacks of ulcerative colitis.

PMID- 11330589
TI  - Ganglioneuromatous polyposis: a premalignant condition. Report of a case and
      review of the literature.
AB  - A 40-year-old man with ganglioneuromatous polyposis and an aggressive coexisting
      colorectal cancer is described. Contrary to previous reports, we believe that
      ganglioneuromatous polyposis should be considered a premalignant condition.

PMID- 11330590
TI  - Squamous-cell carcinoma developing in an ileostomy stoma: report of a case.

PMID- 11330591
TI  - Internal anal sphincter augmentation for fecal incontinence using injectable
      silicone biomaterial.
AB  - PURPOSE: A disrupted or weak internal anal sphincter can lead to passive fecal
      incontinence. This muscle is not amenable to direct surgical repair. Previous
      preliminary attempts to restore functional continuity have included a cutaneous
      flap to fill an anal canal defect, and injection therapy using
      polytetrafluoroethylene, collagen, or autologous fat. Urologists have also used
      injections of collagen or silicone to enhance bladder neck function. This pilot
      study aimed to assess the efficacy of single or multiple injections of the
      silicone-based product Bioplastique for the symptoms of passive fecal
      incontinence caused by an anatomically disrupted or intact but weak internal anal
      sphincter. PATIENTS AND METHODS: Ten patients (6 females; median age, 64, range,
      41-80 years) with passive incontinence secondary to a weak (n = 6) or disrupted
      (n = 4) internal anal sphincter were injected either circumferentially or at a
      single site, respectively. Patients were assessed before and six weeks after
      treatment by clinical assessment, two-week bowel diary card, anorectal
      physiologic testing, and endoanal ultrasound. Patients failing to show
      improvement after the first injection were offered a second injection six weeks
      after the first injection. Clinical assessment was further repeated at six
      months, and five patients had a further ultrasound examination. RESULTS: At six
      weeks, six of ten patients showed either marked improvement (n = 3) or complete
      cessation of leakage (n = 3). A further patient was greatly improved after a
      second injection. Three patients were not improved. At six months, two of the
      seven patients had maintained marked improvement, and one patient had maintained
      minor improvement; all of these three patients had circumferential multiple
      injections. Maximum resting and squeeze anal pressures did not differ
      significantly between before vs. six weeks after vs. six months after injection.
      At six weeks endoanal ultrasound (n = 9) confirmed the presence and correct
      position of the silicone in all but one patient who had experienced obvious
      external leakage of the product. At six months the silicone remained in the
      correct position in the five endosonographically assessed patients. Five of the
      initial patients experienced pain or minor ulceration at the injection site.
      CONCLUSIONS: Although clinically effective immediately after injection, the
      benefit of an injectable biomaterial was maintained in only a minority of
      patients. This occurred despite the continued presence of material in the correct
      anatomical site. Patients with diffuse weakness treated by circumferential
      injection seemed to be the most responsive, but further studies are required to
      clarify this.

PMID- 11330592
TI  - Hyperplastic polyps of the large bowel.

PMID- 11330593
TI  - Intraoperative endoscopy to identify strictures in Crohn's disease.

PMID- 11330594
TI  - Imports banned to guard against foot-and-mouth.

PMID- 11330595
TI  - Owners or guardians?

PMID- 11330596
TI  - AASV guiding members around black holes, in new directions.

PMID- 11330597
TI  - Activists begin legal assault against industrial hog farming.

PMID- 11330598
TI  - Feline practitioners recommend new FIV and FeLV testing guidelines, initiate
      public awareness campaign.

PMID- 11330599
TI  - Love is blind for guide dogs and the veterinarians who care for them. [Interview
      by Lee J. DiVita].

PMID- 11330600
TI  - Practices should take precautions to protect pregnant workers.

PMID- 11330601
TI  - Rabies vaccine recalled because of potency shortfall.

PMID- 11330602
TI  - USDA claims another victory in battle for Vermont sheep.

PMID- 11330603
TI  - Concerned with welfare of dogs in research.

PMID- 11330604
TI  - Thoughts on educational models.

PMID- 11330605
TI  - Thoughts on educational models.

PMID- 11330606
TI  - Another call for diversity in the profession.

PMID- 11330607
TI  - Concerned about the high cost of veterinary treatments.

PMID- 11330608
TI  - Supports returning "star" to veterinary corps.

PMID- 11330609
TI  - Association disagrees with euthanasia method for avian species.

PMID- 11330610
TI  - ECG of the month. Atrial fibrillation in a ram with abomasal emptying defect.

PMID- 11330611
TI  - Leuprolide acetate treatment of adrenocortical disease in ferrets.
AB  - OBJECTIVE: To determine the effects of leuprolide acetate, a long-acting
      gonadotropin-releasing hormone analog, in ferrets with adrenocortical diseases.
      DESIGN: Case series. ANIMALS: 20 ferrets with adrenocortical disease diagnosed on
      the basis of clinical signs and plasma sex hormone concentrations. PROCEDURE:
      Ferrets were treated with leuprolide (100 microg, IM, once), and plasma hormone
      concentrations were measured before and 3 to 6 weeks after treatment. RESULTS:
      Leuprolide treatment resulted in significant reductions in plasma estradiol, 17
      alpha-hydroxyprogesterone, androstenedione, and dehydroepiandrosterone
      concentrations and eliminated or reduced clinical signs associated with
      adrenocortical disease. Decreases in vulvar swelling, pruritus, and undesirable
      sexual behaviors and aggression were evident 14 days after treatment; hair
      regrowth was evident by 4 weeks after treatment. The response to treatment was
      transitory, and clinical signs recurred in all ferrets. Mean +/- SEM time to
      recurrence was 3.7 +/- 0.4 months (range, 1.5 to 8 months). CONCLUSIONS AND
      CLINICAL RELEVANCE: Results suggest that leuprolide can be safely used to
      temporarily eliminate clinical signs and reduce sex hormone concentrations in
      ferrets with adrenocortical diseases. However, the safety of long-term leuprolide
      use in ferrets has not been investigated, and the long-term effects of leuprolide
      in ferrets with nodular adrenal gland hyperplasia or adrenal gland tumors are
      unknown.

PMID- 11330612
TI  - Effects of finasteride on size of the prostate gland and semen quality in dogs
      with benign prostatic hypertrophy.
AB  - OBJECTIVE: To determine the effect of the 5alpha-reductase inhibitor finasteride
      on prostatic diameter and volume, semen quality, and serum dihydrotestosterone
      (DHT) and testosterone concentrations in dogs with spontaneous benign prostatic
      hypertrophy (BPH). DESIGN: Double-blind placebo-controlled trial. ANIMALS: 9 dogs
      with BPH. PROCEDURE: Five dogs were treated with finasteride for 16 weeks (0.1 to
      0.5 mg/kg [0.05 to 0.23 mg/lb] of body weight, PO, q 24 h); the other 4 received
      a placebo. Prostatic diameter, measured radiographically, prostatic volume,
      measured ultrasonographically, semen quality, and serum DHT and testosterone
      concentrations were evaluated before and during treatment. After receiving the
      placebo for 16 weeks, the 4 control dogs were treated with finasteride for 16
      weeks, and evaluations were repeated. RESULTS: Finasteride significantly
      decreased prostatic diameter (mean percentage decrease, 20%), prostatic volume
      (mean percentage decrease, 43%), and serum DHT concentration (mean percentage
      decrease, 58%). Finasteride decreased semen volume but did not adversely effect
      semen quality or serum testosterone concentration. No adverse effects were
      reported by owners of dogs in the study. CONCLUSIONS AND CLINICAL RELEVANCE:
      Results suggest that finasteride can be used to reduce prostatic size in dogs
      with BPH without adversely affecting semen quality or serum testosterone
      concentration.

PMID- 11330614
TI  - Risk factors for development of dysautonomia in dogs.
AB  - OBJECTIVE: To identify risk factors associated with dysautonomia in dogs. DESIGN:
      Case-control study. ANIMALS: 42 dogs with dysautonomia examined between October
      1988 and January 2000 and 132 control dogs examined during the same period for an
      unrelated problem. PROCEDURE: Information was gathered from medical records and
      surveys mailed to owners of case and control dogs. RESULTS: 42 case and 132
      control dogs were included; completed surveys were returned by owners of 30 case
      and 103 control dogs. Dogs with dysautonomia were significantly younger (median,
      18 months) than control dogs (median, 60 months) and more likely to come from
      rural areas and to spend > or =50% of their time outdoors. Compared with rural
      control dogs that spent at least some time outdoors, affected dogs were more
      likely to have access to pasture land, farm ponds, and cattle, and to have
      consumed wildlife, at least occasionally. The largest numbers of dogs with
      dysautonomia were identified during February and April, with relatively few dogs
      identified during the summer and early fall. CONCLUSION AND CLINICAL RELEVANCE:
      Although the cause of dysautonomia is unknown, results suggest that dogs with
      dysautonomia were significantly more likely to live in rural areas and spend > or
      =50% of their time outdoors than were control dogs examined for unrelated
      diseases.

PMID- 11330613
TI  - Pathologic changes in grossly normal menisci in dogs with rupture of the cranial
      cruciate ligament.
AB  - OBJECTIVE: To determine whether histopathologic changes are detectable in grossly
      normal medial menisci from dogs with rupture of the cranial cruciate ligament
      (CCL). DESIGN: Case series. SAMPLE POPULATION: 40 medial menisci from dogs with
      rupture of the CCL and 20 medial menisci from control dogs without stifle joint
      disease. PROCEDURE: Data evaluated included age, duration of clinical signs, and
      whether rupture of the CCL was complete or incomplete. Three groups (n =
      20/group) were also compared on the basis of 5 histologic criteria; group-1
      menisci appeared grossly normal and were obtained from dogs with naturally
      occurring rupture of the CCL, group-2 menisci were grossly abnormal and were also
      obtained from dogs with naturally occurring CCL ruptures, and group-3 menisci
      were collected at postmortem from dogs without stifle joint disease that were of
      similar age and weight as dogs in groups 1 and 2. RESULTS: Group-2 menisci were
      significantly different from group-1 and -3 menisci in all histologic criteria.
      Group-1 menisci were significantly different from control menisci in only 1 of
      the 5 histologic criteria (cartilage differentiation). Dogs that were > or =3
      years old had significantly more surface cellularity than did dogs that were < 3
      years old. A significant difference was not detected between groups 1 and 2 with
      regard to completeness of rupture. CONCLUSIONS AND CLINICAL RELEVANCE: Histologic
      changes in meniscal cartilage correlate with gross appearance of the cartilage at
      time of surgery for rupture of the CCL. On the basis of minimal histologic
      changes, routine removal of grossly normal menisci does not appear to be
      warranted.

PMID- 11330615
TI  - Use of ambulatory electrocardiography for detection of ventricular premature
      complexes in healthy dogs.
AB  - OBJECTIVE: To evaluate the use of 24-hour ambulatory electrocardiography (AECG)
      for the detection of ventricular premature complexes (VPC) in healthy dogs.
      DESIGN: Case series. ANIMALS: 50 healthy mature dogs. PROCEDURE: A 24-hour AECG
      was performed on each dog and evaluated for the presence of VPC. RESULTS: Fifty
      dogs weighing between 18.2 to 40.9 kg (40 and 90 lb) representing 13 breeds were
      evaluated; there were 4 sexually intact females, 21 spayed females, 4 sexually
      intact males, and 21 castrated males. Ages ranged from 1 to 12 years. Thirty-four
      dogs had no VPC; 16 dogs had between 1 and 24 VPC. The grade of arrhythmia ranged
      from 1 to 4, with 4 dogs having an arrhythmia with a grade > 1. Significant
      differences were not detected between the group of dogs with VPC and those
      without VPC with regard to sex, age, and minimum, maximum, or mean heart rate.
      CONCLUSIONS AND CLINICAL RELEVANCE: We conclude that healthy mature dogs have
      infrequent VPC, as detected by use of 24-hour AECG. The presence of numerous or
      sequential VPC may be suggestive of cardiac or systemic disease and may indicate
      the need for thorough clinical evaluation.

PMID- 11330616
TI  - Use of percutaneous ethanol injection for treatment of bilateral hyperplastic
      thyroid nodules in cats.
AB  - OBJECTIVE: To determine the efficacy and safety of percutaneous ethanol injection
      (PEI) for the treatment of hyperthyroidism caused by bilateral hyperplastic
      thyroid nodules in cats. DESIGN; Prospective study. ANIMALS: 7 cats. PROCEDURE:
      Hyperthyroidism was diagnosed on the basis of clinical signs and increased serum
      total thyroxine (TT4) concentrations. The presence of 2 cervical thyroid nodules
      was confirmed by use of ultrasonography and technetium Tc 99m albumin thyroid
      scans. After the death of 1 cat that received PEI in both thyroid nodules at the
      same time, the protocol was changed to injecting ethanol into 1 nodule at a time,
      with at least 1 month between injections. Clinical signs, serum TT4
      concentrations, serum ionized calcium concentrations, laryngeal function,
      findings on ultrasonographic examinations of the ventral cervical region, and
      results of thyroid scans were monitored. RESULTS: Serum TT4 concentrations
      transiently decreased in all 6 cats (into the reference range in 5 of 6 cats)
      within 4 days of the first staged ethanol injection. Each subsequent injection
      resulted in a transient decrease in serum TT4 concentration. The longest period
      of euthyroidism was 27 weeks. Adverse effects included Horner's syndrome,
      dysphonia, and laryngeal paralysis. One cat died of unrelated causes. One cat
      underwent bilateral thyroidectomy, 2 cats were treated with methimazole, and 2
      cats that had increased serum TT4 concentrations were not treated further,
      because they remained clinically normal. CONCLUSIONS AND CLINICAL RELEVANCE:
      Percutaneous ethanol ablation of bilateral thyroid nodules as a treatment for
      cats with hyperthyroidism is not recommended. This treatment is not as
      efficacious as the medical and surgical treatments presently used.

PMID- 11330617
TI  - Percutaneous ethanol injection for treatment of unilateral hyperplastic thyroid
      nodules in cats.

PMID- 11330618
TI  - Mammary duct ectasia in dogs: 51 cases (1992-1999).
AB  - OBJECTIVE: To evaluate the clinical and pathologic characteristics of mammary
      duct ectasia in dogs. DESIGN: Retrospective study. ANIMALS: 51 dogs with mammary
      duct ectasia. PROCEDURE: Information regarding body condition, history, number
      and location of affected mammary glands, appearance of lesions, surgical
      treatment, nonsurgical treatment, and evidence of recurrence or development of
      mammary neoplasia was obtained from surveys sent to referring veterinarians.
      Results of information from examination of histologic sections and referring
      veterinarians were evaluated for all mammary duct ectasia biopsies performed
      between 1992 and 1999. RESULTS: Duct ectasia was the primary diagnosis in 51 of
      1,825 (2.8%) mammary biopsy specimens and comprised 48% of nonneoplastic mammary
      diseases. Affected dogs were evenly distributed over a range of 1 to 13 years of
      age, with a mean age at the time of diagnosis of 6.1 +/- 3.1 years. All dogs were
      female (31 sexually intact, 20 spayed); 10 of 26 had whelped. Duct ectasia was
      described as nodular (26 dogs), cystic (13), and multiglandular (11) and located
      in caudal (31) more often than cranial (14) or middle glands (10). Ectasia
      recurred in 3 dogs. One dog had a history of previously excised mammary
      adenocarcinoma; another subsequently developed mammary carcinoma. CONCLUSIONS AND
      CLINICAL RELEVANCE: Duct ectasia affected mature, sexually intact and spayed
      female dogs over a wide age range. Certain breeds were affected more commonly
      than expected. Increased risk for mammary neoplasia was not evident. Duct ectasia
      should be considered as a cause for mammary enlargement, especially in young dogs
      or when its cystic nature is evident. Mastectomy is usually curative, and
      neoplasia should be ruled out in dogs with ectasia.

PMID- 11330619
TI  - Correlation between leukocytosis and necropsy findings in dogs with immune
      mediated hemolytic anemia: 34 cases (1994-1999).
AB  - OBJECTIVE: To determine whether severity of leukocytosis correlates with severity
      of postmortem lesions in dogs with immune-mediated hemolytic anemia (IMHA).
      DESIGN: Retrospective study. ANIMALS: 34 dogs with IMHA that had CBC performed
      within 48 hours prior to death and complete necropsy examinations. PROCEDURE:
      Dogs were independently assigned to 4 leukocytosis groups (within reference
      range; mild leukocytosis, moderate leukocytosis, marked leukocytosis) and 3
      lesion severity groups (mild lesions, moderate lesions, severe lesions). RESULTS:
      Moderate to marked leukocytosis correlated with moderate to severe postmortem
      lesions. Ischemic necrosis within liver, kidney, heart, lung, and spleen
      attributable to thromboembolic disease or anemic hypoxia were the most common
      important lesions found at necropsy. None of the dogs with mild lesions had
      moderate or marked leukocytosis. Four of 14 severely affected dogs had WBC counts
      within reference range, but all 4 had neutrophilic left shifts. Three of these 4
      dogs had toxic change in neutrophils. CONCLUSION AND CLINICAL RELEVANCE: Moderate
      to marked leukocytosis, neutrophilic left shift, and toxic change in neutrophils
      in dogs with IMHA should alert clinicians to the potential for moderate to severe
      tissue injury, which could complicate treatment and worsen prognosis. Lesions
      appear to be secondary to anemic hypoxia, thromboembolic disease, or both;
      therefore, treatment objectives should focus on improving blood oxygen-carrying
      capacity and monitoring for thromboembolic disease.

PMID- 11330620
TI  - Comparison of immediate intradermal test reactivity with serum IgE quantitation
      by use of a radioallergosorbent test and two ELISA in horses with and without
      atopy.
AB  - OBJECTIVE: To compare a radioallergosorbent test and 2 ELISA with intradermal
      testing for the determination of environmental allergen hypersensitivity in
      horses with and without atopic diseases. DESIGN: Prospective clinical study.
      ANIMALS: 10 horses with recurrent urticaria, 7 with atopic dermatitis, 16 with
      chronic obstructive pulmonary disease, and 22 without atopy. PROCEDURE: History,
      physical examination, hemogram, serum biochemical analyses, bronchoalveolar
      lavage, and an intradermal test (used as the criterion standard) with a regional
      panel of 73 allergens were performed in all horses. Serum was analyzed by use of
      the 3 in vitro assays of allergen-specific IgE. RESULTS: An ELISA based on the
      alpha chain of the high-affinity IgE receptor, the Fcepsilon receptor
      immunoglobin epsilon chain (FcepsilonRIalpha) for IgE, had the overall highest
      kappa statistic (0.238), positive predictive value (49%), and negative predictive
      value (78%). Overall agreement between the FcepsilonRIalpha-based ELISA and the
      intradermal test was fair. The highest kappa statistic was obtained by the
      FcepsilonRIalpha-based ELISA in horses with atopic dermatitis (0.330). Kappa
      statistics for the radioallergosorbent test and a polyclonal antibody-based ELISA
      agreed slightly with that of the intradermal test at best. CONCLUSIONS AND
      CLINICAL RELEVANCE: None of the 3 serum allergy tests reliably detected allergen
      hypersensitivity, compared with the intradermal test. The FcepsilonRIalpha-based
      ELISA performed significantly better overall than the other 2 tests. Low
      sensitivity of all 3 assays indicates the need for continued study to elucidate a
      more sensitive test for the determination of potentially pathogenic allergens in
      horses.

PMID- 11330621
TI  - Use of canaliculorhinostomy for repair of nasolacrimal duct obstruction in a
      horse.
AB  - Obstruction of the nasolacrimal outflow pathway in horses is not uncommon. Causes
      of obstruction include foreign bodies, trauma, and congenital abnormalities.
      Placement of a nasolacrimal retention stylette may prove challenging.

PMID- 11330622
TI  - Association of herd productivity and bulk-tank somatic cell counts in US dairy
      herds in 1996.
AB  - OBJECTIVE: To assess the association of bulk-tank somatic cell counts (BTSCC) and
      the value of herd productivity (milk produced, calves born, and net costs for cow
      replacements) in US dairy herds in 1996. DESIGN: Randomized stratified national
      survey of dairy producers. SAMPLE POPULATION: Records from 1,219 dairy herds in
      the top 20 dairy states. PROCEDURE: Responses for 1,178 herds had complete
      information for economic analysis. Per-cow value of production was determined for
      each herd. Data for herds with high (> or = 400,000 cells/ml) and medium (200,000
      to 399,999 cells/ml) BTSCC were compared with values for herds with low BTSCC (<
      200,000 cells/ml), using a multivariable regression model. RESULTS: In 1996, milk
      was priced at $0.287/kg ($13/cwt). Herds with low BTSCC annually generated
      $103.90/cow more in herd productivity than herds with medium BTSCC and
      $292.39/cow more than herds with high BTSCC. CONCLUSIONS AND CLINICAL RELEVANCE:
      Increased BTSCC (> 200,000 cells/ml) were associated with a reduced value of
      productivity per cow. Thus, dairy producers have a financial incentive to seek
      out and implement cost-effective management practices that will enable them to
      decrease their BTSCC to < 200,000 cells/ml and maximize herd productivity.

PMID- 11330623
TI  - Mitochondrial gene expression in diabetes mellitus: effect of nutrition.
AB  - Diabetes mellitus is a collection of genetic diseases that share a common
      phenotype: glucose intolerance. The genetic origins of this disease are being
      widely investigated. An estimated 0.19% of the population with diabetes has the
      disorder owing to one or more mutations in the mitochondrial genome. Diet can
      affect the expression of the genome as well as the function of its gene products.
      The antioxidant nutrients serve to protect this very vulnerable genome from
      oxidative damage. These nutrients may affect mitochondrial DNA transcription and
      nutrients that affect membrane fluidity affect the function of the gene products.

PMID- 11330624
TI  - Recommending calcium to reduce lead toxicity in children: a critical review.
AB  - Assertions that adequate or supplemental calcium intake can reduce lead
      absorption in children are based on liberal extrapolation from animal studies,
      experiments with human adults, and cross-sectional studies of children that have
      a variety of methodologic weaknesses. Without stronger supporting evidence,
      statements that diet can ameliorate the deleterious effects of environmental lead
      could provide a false sense of efficacy and divert efforts from lead abatement
      and from behavioral modifications that might have more impact.

PMID- 11330625
TI  - Identifying populations at risk of zinc deficiency: the use of supplementation
      trials.
AB  - Zinc supplementation trials assessing the response of growth and immunity have
      assisted in identifying populations at risk of zinc deficiency and the factors
      that contribute. A recent trial in Ethiopia demonstrated a high risk of zinc
      deficiency among young children, particularly among those who were stunted.

PMID- 11330626
TI  - Dietary fiber and colorectal cancer: what is appropriate advice?
AB  - Two recent studies question the role of dietary fiber in the prevention of
      colorectal cancer. However, the duration of dietary intervention, dose of fiber,
      and the complexity of polyp formation and transformation to carcinomas make
      interpretation of such studies difficult. Multiple rationales exist for promoting
      the consumption of high-fiber, low-fat, fruit- and vegetable-rich diets.

PMID- 11330627
TI  - To feed or not to feed: tube feeding in patients with advanced dementia.
AB  - Caring for demented patients with eating difficulties poses formidable challenges
      to health care providers and family members. Tube feeding has been routinely used
      in this situation to improve survival and functional status, to prevent or
      decrease consequences of malnutrition and wasting, and to provide comfort and
      palliation. However, a recent comprehensive review on this issue provides
      convincing arguments against the routine use of tube feeding in advanced
      dementia. At present, no data exist to support the theory that tube feeding
      improves any of the important clinical outcomes. More importantly, tube feeding
      is associated with significant rates of morbidity and mortality. The use of tube
      feeding should be highly individualized and appropriately used after careful
      assessment of the benefits and risks of such therapy, and with specific short-
      and long-term goals in mind.

PMID- 11330628
TI  - Remarks from Dan Glickman, Secretary of Agriculture.

PMID- 11330629
TI  - How and why do individuals make food and physical activity choices?

PMID- 11330630
TI  - Environmental and societal factors affect food choice and physical activity:
      rationale, influences, and leverage points.

PMID- 11330631
TI  - Summit on promoting healthy eating and active living: developing a framework for
      progress. Washington, DC, USA. April 25-26, 2000.

PMID- 11330632
TI  - Remarks from David Satcher, M.D., Ph.D., Assistant Secretary for Health and
      Surgeon General.

PMID- 11330633
TI  - Nitric oxide: a novel mediator of sperm function.

PMID- 11330634
TI  - Are we falling behind in the stem cell race?

PMID- 11330635
TI  - Interpreting positive studies.
AB  - When examining the results of a positive research study, one needs to consider
      two issues of clinical relevance. First, is the outcome measure of direct
      interest to patients, or is it clearly linked to a measure of direct interest to
      patients? Second, is the difference large enough to lie outside the range of
      clinical indifference? Don't accept the findings of a positive research study
      without a careful consideration of clinical relevance.

PMID- 11330636
TI  - A fragment of prosaposin (SGP-1) from rooster sperm promotes sperm-egg binding
      and improves fertility in chickens.
AB  - A protein isolated from the supernatant of cryopreserved rooster sperm was found
      to increase the capability of cryopreserved rooster sperm to bind in vitro to the
      perivitelline membrane of a chicken egg and substantially raise fertility after
      artificial insemination (AI). That activity was partially purified and termed
      universal primary sperm-egg binding protein (UPSEBP). Insufficient protein
      remained from 6 x 10(11) sperm, despite retention of bioactivity, to allow
      sequencing. We deduced that the protein may be related to prosaposin (also termed
      SGP-1, for sulfated glycoprotein-1), and we used published amino acid sequences
      of prosaposin as a guide for synthesis of peptides. Certain peptides were found
      to increase in vitro sperm-egg binding and increase fertility of frozen-thawed or
      fresh rooster sperm, in a manner similar to semipurified UPSEBP. Active epitopes
      were in a 60 amino acid sequence, reflecting the intervening sequence between
      saposins A and B, plus short extensions into saposins A and B. Highest activity
      was found when this synthetic peptide was oxidized to form a disulfide bond
      between terminal cysteines. Antibody against a synthetic peptide consisting of 58
      of these 60 amino acids bound to a 7-9 kilodalton protein in UPSEBP.
      Collectively, the data support the conclusion that UPSEBP is a fragment of
      prosaposin. Because prosaposin is in semen in humans and animals, these
      observations have broad implications for possible cause and therapy of one type
      of subfertility.

PMID- 11330637
TI  - Morphology of testicular spermatozoa obtained by testicular sperm extraction in
      obstructive and nonobstructive azoospermic men and its relation to fertilization
      success in the in vitro fertilization-intracytoplasmic sperm injection system.
AB  - The aim of the present study was to evaluate the morphology of testicular
      spermatozoa by 3 different determinants. Sperm cells were obtained and their
      morphology was evaluated from 27 testicular sperm extraction (TESE) operations,
      of which 20 men had nonobstructive azoospermia and 7 had obstructive azoospermia.
      In 17 cases, 2 biopsies were obtained from 2 different locations of the testis.
      Only mature spermatozoa presenting full-grown tail (tail dimension about 10-fold
      greater than the head dimension) were counted. Three characteristics of sperm
      morphology were evaluated: head dimensions, and acrosome and midpiece
      irregularities. The percentage of sperm cells with normal morphology (considering
      the 3 characteristics) in specimens from patients with obstructive and
      nonobstructive azoospermia were 47% +/- 4.6% and 29 +/- 1.8%, respectively (P <
      .01). The percentage of spermatozoa with normal head dimensions were 76% +/- 3.2%
      and 63% +/- 2.6% (P > .05), those with normal acrosome were 58% +/- 4.6% and 41%
      +/- 3.4% (P < .05), and those with normal midpiece were 74% +/- 4.1% and 67% +/-
      1.6% (P > .05), in obstructive and nonobstructive azoospermia, respectively. No
      significant differences were observed in sperm morphology between different
      locations of the testis. Sperm morphological characteristics were not associated
      with fertilization rate in intracytoplasmic sperm injection (ICSI). Follicle
      stimulation hormone and luteinizing hormone were inversely correlated with normal
      morphology of testicular spermatozoa (r = -0.49 and r = -0.47, respectively; P <
      .05). It can be concluded that a relatively high portion of testicular sperm are
      morphologically normal. The higher rate of normal spermatozoa in obstructive
      azoospermia compared with nonobstructive spermatozoa suggests that the factors
      leading to azoospermia may affect testicular sperm morphology. The morphological
      characteristics of testicular sperm do not affect fertilization rate in ICSI.

PMID- 11330638
TI  - Morphologically distinct sperm subpopulations defined by Fourier shape
      descriptors in fresh ejaculates correlate with variation in boar semen quality
      following cryopreservation.
AB  - This study investigated two hypotheses: 1) that consistent between-boar variation
      in frozen semen quality exists and is genetically determined, and 2) that
      morphologically distinct subpopulations of spermatozoa exist within fresh boar
      ejaculates and that the incidence of these subpopulations is correlated with
      semen quality following cryopreservation. Five ejaculates were collected from
      each of 15 boars (5 boars from each of 3 breeds). An objective sperm morphology
      analyzer used Fourier shape descriptors to describe variation in the morphology
      of 300 spermatozoa per ejaculate before freezing. Semen was diluted into a
      commercial freezing buffer (700 mOsm/kg, 3% glycerol) and 5 straws (0.5 mL) per
      ejaculate were cryopreserved (to -5 degrees C at 6 degrees C/min, then -5 degrees
      C to -80 degrees C at 40 degrees C/min). Semen was assessed for percentage of
      motile cells and motility characteristics (with computer-aided sperm analysis),
      plasma membrane integrity (SYBR-14 positive), and acrosome integrity (fluorescein
      labeled peanut agglutinin positive). Consistent between-boar variability was
      detected for post-thaw sperm motility (P < .01), membrane integrity (P < .01),
      acrosome integrity (P < .01), curvilinear velocity (P < .01), straight-line
      velocity (P < .05), beat cross-frequency (P < .05), and amplitude of lateral head
      displacement (P < .01). Three morphologically distinct subpopulations of
      spermatozoa, defined by Fourier descriptors, were detected. The proportion of
      these subpopulations within the fresh ejaculate correlated with semen quality
      assessments made following cryopreservation. These findings support the
      hypothesis that consistent interindividual variation in sperm freezability is
      genetically determined and may relate to processes that occur during
      spermatogenesis. Subsequent characterization of these genetic differences between
      "good" and "poor" freezers may ultimately identify biophysical components of the
      spermatozoa that are essential for successful cryopreservation.

PMID- 11330639
TI  - Characterizing the reproductive physiology of the male southern black howler
      monkey, Alouatta caraya.
AB  - Limited reproductive data are available for any species of howler monkey,
      including those listed as threatened (Alouatta pigra) and endangered (A.
      palliata) by the Convention on International Trade in Endangered Species Status
      (CITES) report. The Southern black howler monkey (A. caraya) is being considered
      as a model species to develop assisted reproductive technology (ART) for
      vulnerable howler species. Specific objectives of this study were to evaluate the
      effect of 1) time of year on ejaculate quality and testosterone concentration, 2)
      age of male on ejaculate quality, and 3) seminal plasma on sperm longevity in
      vitro. Three adult (4.5 to 5 years) and 3 subadult (1.5 to 2.5 years) males were
      evaluated for a 1.5-year period. Semen samples were obtained by
      electroejaculation, and testosterone levels were monitored by fecal steroid
      metabolite radioimmunoassay. Males produced coagulum-free ejaculates throughout
      the year. Likewise, most (4/6) males exhibited constant testosterone levels (3.66
      +/- 0.45 ng/g) during the year. Testosterone levels for the remaining 2 males,
      housed as a bachelor troop, were elevated (43 ng/g) during the months of May and
      June. Seminal characteristics were similar (P > .05) between age groups. Average
      semen volume was higher during the summer months (P < .05). Sperm concentrations
      were highly variable through the year and ranged from 7.0 x 10(6) sperm/mL to
      583.0 x 10(6) sperm/mL. Percentages of motile sperm (73% +/- 2.3%) and forward
      progressive sperm motility (3.3 +/- 0.1), however, were consistent (P > .05)
      throughout the year. The average pH (8.9 +/- 0.1) and osmolality (356.7 +/- 26.1
      mmol/kg) of raw semen also did not vary (P > .05) throughout the year. Ejaculates
      from subadult males, however, contained more (P < .05) morphologically abnormal
      spermatozoa than adult ejaculates. In addition, in vitro sperm longevity was poor
      (<2 hours) for subadult male samples, regardless of the presence or absence of
      seminal plasma (P > .05). For adult males, seminal plasma was detrimental to
      sperm longevity; however, spermatozoa survived more than 5 hours in vitro when
      seminal plasma was removed. Although subadult males produce semen, these
      ejaculates would not be ideal for further characterization of seminal traits or
      development of ART for other howler monkey species.

PMID- 11330640
TI  - Dual energy metabolism-dependent effect of Ureaplasma urealyticum infection on
      sperm activity.
AB  - Genital Ureaplasma urealyticum infection is considered a sexually transmitted
      infection. It has long been debated whether the presence of U. urealyticum in
      semen may be a possible cause of infertility. Long-term incubation (4 hours or
      overnight) of sperm cells with U. urealyticum in vitro resulted in a significant
      inhibition of sperm motility and membrane alteration whereas a short incubation
      (45 minutes) of sperm cells with ureaplasmas resulted in an acceleration of sperm
      velocity. The aim of this study was to understand these contradictory reports of
      U. urealyticum infection on sperm motility. Spermatozoa from fresh ejaculates of
      normozoospermic semen of men who were referred to the university Male Fertility
      Laboratory for semen analysis, with no history of genital tract infection, and
      from normal Assaf breed rams were infected in vitro with U. urealyticum serotype
      8, at different pHs and O2 concentrations. Sperm viability and motility and
      changes in extracellular pH were evaluated. A significant (16%-43%) increase in
      sperm activity was observed upon infection at alkaline pH (7.8) under aerobic or
      hypoxic conditions, and a 58% increase was observed under anaerobic conditions
      and pH 7.2. When the infection was conducted under aerobic conditions and acidic
      pH (6.3), or under hypoxic conditions at neutral pH (7.2), an 8%-25% inhibition
      of sperm activity was observed. These results indicate that when sperm activity
      depends on mitochondrial oxidative phosphorylation, usually at low pHs, U.
      urealyticum competes with mitochondrial energy production and therefore reduces
      sperm motility and viability. However, when sperm energy metabolism depends on
      glycolysis, usually at higher pHs, U. urealyticum stimulates glycolysis and sperm
      activity.

PMID- 11330641
TI  - Neonatally administered diethylstilbestrol retards the development of the blood
      testis barrier in the rat.
AB  - Newborn rats were treated with 10 microg of diethylstilbestrol (DES) on alternate
      days from the 2nd to the 12th postnatal day, and the testes were sequentially
      examined up to 105 days of age by light, electron, and confocal laser microscopy.
      In control rats, spermatozoa and step 19 spermatids were observed in stage VIII
      seminiferous tubules at 56 days of age. Spermatogenic cells in DES-treated rats
      differentiated normally from birth until 21 days of age, after which
      differentiation continued only to the pachytene-spermatocyte stage. From this age
      onward, spermatogenic cells older than pachytene spermatocytes were not found
      until 56 days of age. After this point, the cells resumed differentiation and
      finally became spermatozoa by 91 days of age; that is, 35 days later than control
      rats. Electron and confocal laser microscopy showed that in the normal rat, the
      formation of the ectoplasmic specialization between adjoining Sertoli cells was
      observed as early as 20 days of age. In contrast, the specialization was not
      formed until 56 days of age in DES-treated rats. Furthermore, the delay in
      functional maturation of this structure as the blood-testis barrier was confirmed
      by intercellular tracer experiments. It is clear that neonatal administration of
      DES delayed the establishment of the blood-testis barrier for 4 weeks.
      Consequently, during this period, pachytene spermatocytes were exfoliated from
      the seminiferous epithelium without completion of meiosis.

PMID- 11330642
TI  - Chromatin structure in globozoospermia: a case report.
AB  - Sperm nuclear abnormalities in patients with globozoospermia have not been well
      characterized and may lead to the high rates of fertilization failure and embryo
      loss reported in patients with this form of teratozoospermia. This study used
      transmission electron microscopy (TEM), the sperm chromatin structure assay
      (SCSA), and single cell gel eletrophoresis assay (COMET) to assess if
      globozoospermia is associated with sperm chromatin structure abnormalities, DNA
      fragmentation, or both. The flow cytometric SCSA measures abnormal chromatin
      structure based on the susceptibility of sperm nuclear DNA to acid-induced
      denaturation in situ. COMET measures DNA fragmentation in individual sperm nuclei
      based upon gel electrophoretic patterns. Although sperm concentration (113
      million/mL) and motility (66%) were normal in the patient, there was complete
      acrosome deficiency. TEM and SCSA data confirmed light microscopic examination
      that showed that sperm populations included a mixture of round and elongated
      sperm heads. Even though 100% of sperm had abnormal head morphology, only 13%
      demonstrated DNA denaturation (COMPalpha(t)), which is below our threshold of 15%
      COMPalpha(t), and consistent with high-fertility patients. Of interest, 13% of
      the sperm were also positive in the COMET assay, supporting our previous
      observations that SCSA-positive cells are also positive for DNA fragmentation. It
      was unexpected but of great interest that a human sperm population with 100%
      sperm morphology abnormalities had a chromatin integrity at the molecular level
      that is equivalent to sperm populations shown in previous studies to be highly
      fertile. These data are the first reported using SCSA and COMET assays to
      evaluate a patient with globozoospermia and support previous reports that
      intracytoplasmic sperm injection of globozoospermia may result in
      fertility/pregnancy. Lower success rates seen in some patients may be due to
      unrelated factors.

PMID- 11330643
TI  - Epidermal growth factor modulates the expression of vascular endothelial growth
      factor in the human prostate.
AB  - The growth and dissemination of tumors in the body has been associated with
      angiogenesis. Vascular endothelial growth factor (VEGF) is an angiogenic factor
      that stimulates endothelial cell growth and enhances vascular permeability. VEGF
      exerts its action by binding to specific cell surface receptors. Three receptors,
      VEGFR-1 (flt-1), VEGFR-2 (flk-1), and VEGFR-3 (flt-4) have been identified. Very
      little information on the coordinated expression of VEGF and its receptors in
      normal prostate, benign prostatic hyperplasia (BPH), and prostate carcinoma is
      available. Therefore, we examined the immunohistochemical localization of VEGF
      and its receptors in tissues derived from normal human prostate, BPH, and
      prostatic carcinoma. Immunostaining for VEGF was absent in the normal prostate.
      Epithelium lining the glands of prostate derived from patients with BPH exhibited
      strong immunostaining. The intensity of staining was relatively less in prostate
      carcinoma. It is interesting that VEGFR-1 and VEGFR-3 were strongly expressed in
      both stromal and epithelial tissues in normal prostate, BPH, and carcinoma. In
      comparison, VEGFR-2 was not localized to normal prostate and its expression in
      the stroma of BPH and epithelium of carcinoma was very weak. Because progression
      of prostate cancer is accompanied by altered expression of epidermal growth
      factor (EGF) and its receptor (EGFR) in malignant cells, we investigated the
      effect of EGF on VEGF gene expression by Northern blot analysis in 2 human
      prostate cancer cell lines that express EGFR. EGF greatly enhanced the expression
      of VEGF messenger RNA in DU145 and PC3 cell lines in a dose-dependent manner. The
      EGF induction of VEGF gene expression suggests a mechanism by which angiogenesis
      could be accelerated in BPH and prostate carcinoma.

PMID- 11330644
TI  - Larger trinucleotide repeat size in the androgen receptor gene of infertile men
      with extremely severe oligozoospermia.
AB  - Androgens are significant regulators of human spermatogenesis. Their action is
      mediated through the androgen receptor (AR), which binds to the androgen
      responsive element on DNA and regulates gene transcription. Men become infertile
      with spinobulbar muscular atrophy (Kennedy disease) caused by a trinucleotide
      repeat expansion, > or = 40 CAG repeats, in the AR gene located on the X
      chromosome. In this prospective study, we investigated whether the variable size,
      larger repeats, of this trinucleotide could alter AR function and result in
      impaired spermatogenesis. A total of 69 infertile men were studied. Clinical and
      laboratory analysis showed idiopathic, nonobstructive azoospermia in 16 men,
      extremely severe oligozoospermia in 27 men (< 1 million sperm/mL), and severe
      oligozoospermia in 26 men (1 to 5 million sperm/mL). Fertile control men (n = 45)
      were selected by documented paternity proven by linkage analysis. Leukocyte DNA
      was analyzed by polymerase chain reaction (PCR) amplification across the AR
      repeat region. Accurate size determination of the PCR product using an ABI 373
      DNA sequencer allowed precise calculation of CAG repeat sizes. The AR gene was
      not analyzed for other types of mutations. The difference in CAG repeat size
      between infertile men and proven fertile controls was statistically significant,
      P = .03. Patients with extremely severe oligozoospermia had significantly longer
      CAG repeat tracts (mean, 25.4 +/- 4.0; P = .0005; range 20-39) than controls
      (mean, 22 +/- 2.8; range 12-30) or patients with severe oligozoospermia (mean,
      22.2 +/- 2.3; range 18-26). None of the 26 infertile men with sperm counts < 1
      million/mL had < or = 19 CAG repeats compared with 6 out of 45 controls (13%; P =
      .06). This study suggests that some men with severe impairment of spermatogenesis
      have longer trinucleotide repeats in the AR gene. Although direct evidence is
      missing, lower affinity between androgen and the AR protein or decreased AR
      protein availability with longer repeats could be responsible for a diminished
      androgen effect on spermatogenesis. Two of the patients in the extremely severe
      oligozoospermia group had 35 and 39 CAG repeats, respectively (normal range is 11
      to 33). Although not yet considered a mutation, longer trinucleotide repeats are
      unstable and might either expand or contract between generations. If they expand,
      conception through the use of intracytoplasmic sperm injection (ICSI), could
      result in the son of an

PMID- 11330645
TI  - Regulation of caltrin mRNA expression by androgens in the murine prostate.
AB  - Testicular androgens induce the proliferation and differentiation of prostatic
      epithelial cells by regulating the expression of androgen target genes. The use
      of subtractive hybridization to isolate genes that are differentially expressed
      during the early phase of androgen-induced prostatic regrowth in castrated mice
      resulted in identification of the murine caltrin gene. Caltrin messenger RNA
      (mRNA) was highly expressed in the prostates of intact mice. Five weeks following
      castration of mice, steady state caltrin mRNA levels were reduced by 70%. Within
      12 hours of administration of pharmacological doses of testosterone enanthate,
      steady state caltrin mRNA levels were elevated and increased to 90% of levels
      found in intact mice by 24 hours. Reverse transcriptase-polymerase chain reaction
      analysis of prostate tissue localized caltrin mRNA transcripts to the dorsal but
      not the ventral or lateral prostate. Within the dorsal prostate, in situ
      hybridization always localized caltrin mRNAs to the prostatic epithelial cells.
      Testosterone-induced increases in caltrin mRNA levels were detected prior to S
      phase progression and initiation of proliferation in this cell population.
      Caltrin has been demonstrated previously to function as a calcium transport
      inhibitor at the plasma membrane. Findings of this study indicate that caltrin is
      highly expressed and androgen-regulated in the murine prostate, where it is
      associated with androgen-induced proliferation and differentiation of epithelial
      cells.

PMID- 11330646
TI  - Accessory sperm as an indication of fertilizing ability of rabbit spermatozoa
      frozen in egg yolk-acetamide with detergent.
AB  - Many factors besides initial semen quality affect fertilization rates as sperm
      interact with the environment of the female reproductive tract. One of these
      factors is sperm transport, which can be evaluated by accessory sperm counts.
      Dutch rabbits were used to test the effects on sperm transport, fertilization,
      and production of young when sodium and triethanolamine lauryl sulfate (STLS)
      detergent was added to a medium for sperm cryopreservation. When STLS was added
      in 10 concentrations ranging from 0% to 2.0% (vol/vol) to an egg yolk-acetamide
      semen extender, optimal post-thaw motility of rabbit sperm occurred when 0.2% to
      0.7% STLS was included. However, when 0%, 0.2%, and 0.7% STLS was included to
      cryopreserve sperm used for insemination, the fertilization rates were 95%, 68%,
      and 75%, and the corresponding mean numbers of accessory sperm per embryo were
      13.1, 1.7, and 0.4 (P < .05). In another experiment, increasing the acetamide
      concentration from 0.75 M to 1.25 M decreased fertilization rates from 66% to
      35%, and was associated with 4.5 and 0.6 accessory sperm per embryo (P < .05). In
      the final experiment, 48 does inseminated with sperm cryopreserved with 0%,
      0.35%, and 0.70% STLS were allowed to produce young. Corresponding pregnancy
      rates were 56%, 56%, and 31% (P < .05), and litter sizes were 5.6, 4.1, and 4.2
      (P > .05). In these studies, low concentrations of STLS improved motility of
      frozen-thawed sperm, but fertilization and pregnancy rates were reduced. Sperm
      transport was correspondingly reduced, and the accessory sperm count provided a
      reliable measure of the effect of STLS on fertility in contrast to the assessment
      of the percentage of motile sperm.

PMID- 11330647
TI  - Susceptibility of glycolytic enzyme activity and motility of spermatozoa from
      rat, mouse, and human to inhibition by proven and putative chlorinated
      antifertility compounds in vitro.
AB  - Nonhormonal contraceptives that act by blocking energy metabolism within sperm
      have the advantage over spermatogenic inhibitors by their fast onset of
      infertility and their almost immediate restoration of fertility after withdrawal
      of the contraceptive agent. This study was done to test new chlorinated compounds
      for their contraceptive potency on rodent and human sperm in vitro. Cells were
      incubated in a medium containing glucose as the sole energy source with 1-chloro
      3-hydroxypropanone (CHOP) and 1,6-dichloro-1,6-dideoxy-D-fructose (DCDF),
      chlorinated analogues of glycolytic substrates, as well as racemic (R,S)-alpha
      chlorohydrin (ACH). After incubation, enzymatic activity and kinematic parameters
      were estimated. A dose-dependent inhibition of the glycolytic enzyme,
      glyceraldehyde 3-phosphate dehydrogenase (GAPDH), of rat and mouse distal cauda
      epididymidal and human ejaculated sperm by ACH, CHOP, and DCDF was demonstrated.
      Triosephosphate isomerase (TPI) was inhibited by ACH, but not by CHOP and DCDF,
      irrespective of species. All compounds inhibited sperm motility and kinematic
      parameters with increasing concentration. The results confirm that inhibition of
      glycolytic enzymes of sperm, including those of human, can be effectively brought
      about by a variety of chloro-compounds that can be converted to (S)-3
      chlorolactaldehyde, the stereospecific chloro-derivative of the enzyme's natural
      substrate, (R)-glyceraldehyde 3-phosphate, and could be developed into
      contraceptive agents for men.

PMID- 11330648
TI  - Differential expression of CCAAT/enhancer-binding protein-delta (c/EBPdelta) in
      rat androgen-dependent tissues and human prostate cancer.
AB  - CCAAT/enhancer-binding protein delta (C/EBPdelta) is a nuclear transcription
      factor that regulates cellular growth and differentiation. In this study we
      demonstrate that C/EBPdelta gene expression is differentially regulated in rat
      androgen-dependent tissues and human prostate cancer. C/EBPdelta messenger RNA
      (mRNA) levels were very low in adult rat ventral prostate, epididymis, and
      testis. In ventral prostate and epididymis, expression of C/EBPdelta mRNA
      increased more than sixfold when testicular testosterone was eliminated by
      surgical castration or treatment with ethane-1,2-dimethanesulfonate (EDS).
      Testosterone replacement reduced C/EBPdelta mRNA levels to near control values in
      both tissues. CWR22 is a human prostate cancer xenograft that mimics biological
      characteristics of androgen-dependent and androgen-independent human prostate
      cancer. In androgen-dependent CWR22 tumors, expression of C/EBPdelta mRNA
      declined in response to castration. Both C/EBPdelta mRNA and protein levels
      increased following testosterone administration. However, C/EBPdelta mRNA and
      protein levels were variable in recurrent CWR22 tumors growing in the absence of
      testicular androgen for approximately 5 months. C/EBPdelta expression was also
      variable in androgen-independent human prostate carcinomas (n = 3), although mRNA
      levels were substantially lower than those in androgen-dependent tumors (n = 3).
      These studies demonstrate that androgen down-regulates C/EBPdelta levels in
      androgen-dependent rat tissues, but induces C/EBPdelta expression in androgen
      dependent human prostate cancer. Deregulation of C/EBPdelta occurs when prostate
      cancer progresses to the androgen-independent state.

PMID- 11330649
TI  - Properties of a new, long-lasting vaginal delivery system (LASRS) for
      contraceptive and antimicrobial agents.
AB  - In view of the need for improved vaginal formulations that are contraceptive,
      that may prevent transmission of sexually transmitted infections, or both, a new
      delivery system (base formulation; called Long Acting, Sustained Release of
      Spermicide, or LASRS) was developed that contains bioadhesive and other
      ingredients with a long history of safety, and was designed to provide long
      lasting vaginal retention of the formulation and to minimize possible vaginal
      irritation caused by incorporated active ingredients. Nonoxynol-9 (N-9) was added
      as an active ingredient to study the vaginal irritating properties of the
      formulation and to assess its long-term effectiveness by postcoital spermicidal
      tests. In the first series of experiments, in vitro studies showed that the
      formulation spreads rapidly over a cellulose membrane, forming a bioadhesive
      layer that remained for at least 12 hours. The second series of experiments
      addressed the safety of the LASRS suppository in rabbits and primates. Even with
      a very high concentration of N-9 (20.5%), LASRS caused only mild/moderate but
      acceptable irritation in the rabbit. No vaginal irritation occurred in the
      primate at an even higher concentration (22.5%). During the third series of
      experiments, the long-lasting vaginal retention properties were evaluated by
      postcoital spermicidal tests in the primate. LASRS with N-9 was highly
      spermicidal even when mating was delayed for 12 hours after placement of the
      formulation. Spermicidal activity was also observed when 1) mating was delayed
      for 24 hours after insertion of the formulation, and 2) if the females were mated
      2 or even 3 times without reinsertion of the suppository before collection of the
      vaginal contents. In the final series of tests, the postcoital spermicidal
      properties of menfegol, another cytotoxic spermicide, were evaluated as were
      several modifications in the base formulation. Menfegol produced essentially the
      same results as N-9. Altering the base formulation proved to be nonbeneficial
      because a decrease in the long-term spermicidal effectiveness was obtained. These
      results suggest that the LASRS suppository has good vehicle properties for the
      delivery of active ingredients to the vagina.

PMID- 11330650
TI  - Leptin secretion from the epididymal fat pad is increased by the sexual
      maturation of the male rat.
AB  - Although leptin has been implicated as an important factor in triggering the
      onset of puberty in females, much less is known about the role of this adipose
      tissue hormone in the sexual maturation of males. Previous work in the rat has
      suggested that the peripubertal rise in testosterone precedes an increase in
      leptin secretion, and it has been suggested that the testosterone rise induces
      the leptin increase. These studies examined some of the interactions between
      leptin secretion and the peripubertal testosterone rise in male rats. Serum
      leptin concentrations were significantly elevated in young adult male rats
      compared with immature rats. Cultured epididymal fat pads obtained from adult
      animals secreted significantly more leptin than did those obtained from immature
      rats. Castration of immature rats with or without testosterone replacement for 1
      week did not result in a significant change in either the serum leptin
      concentrations or the ability of the epididymal fat pad to secrete leptin.
      Exposure of epididymal fat to 5 ng/mL of testosterone in vitro resulted in a
      significantly enhanced secretion of leptin into the media compared with plain
      media controls. These results confirmed that there is an increase in serum leptin
      concentrations with sexual maturation in the male rat. They also suggest that
      this increase is due to an enhanced ability of adipose tissue to secrete leptin.
      Within a normal physiologic range, testosterone may play a role in inducing this
      increased ability to secrete leptin.

PMID- 11330651
TI  - Evaluation of nitric oxide synthase and arginase in the induction of a Peyronie's
      like condition in the rat.
AB  - Peyronie's disease is an idiopathic, localized connective tissue disorder of the
      penis, involving the tunica albuginea of the corpus cavernosum and adjacent
      areolar space. Current proposals as to the origin of Peyronie's disease suggest
      that fibrosis and collagen changes of the tunica are the result of an
      inflammatory process following vascular trauma. Our laboratory and other
      investigators have recently proposed an animal model for the study of Peyronie's
      disease. When transforming growth factor-beta1 (TGF-beta1) was injected into the
      rat tunica albuginea, tissue fibrosis was observed at 6 weeks. Therefore, our aim
      was to assess arginase II, endothelial and inducible nitric oxide synthase
      isoforms, and nitrotyrosine levels--all factors involved in inflammatory
      reactions--in the cavernosal tissue of saline-injected and TGF-beta1-injected
      rats after 6 weeks in order to evaluate the roles these enzymes may play in the
      induction of a Peyronie's-like condition in the rat. To examine the expression of
      endothelial nitric oxide synthase (eNOS), iNOS, and arginase II protein, and mRNA
      in the corpus cavernosum, immunoblot analysis, and reverse transcriptase
      polymerase chain reaction were performed. We also determined
      immunohistochemically the expression of nitrotyrosine, a marker of peroxynitrite
      formation, in the rat penis. After 6 weeks, iNOS protein and gene expression was
      up-regulated and eNOS protein and gene expression was down-regulated in the
      corpora cavernosa of the TGF-beta1-injected penises. Furthermore, arginase II
      protein expression as well as immunohistochemical localization of nitrotyrosine
      was significantly higher in the TGF-beta1-injected corpora cavernosa. These
      results suggest that iNOS is the key control element for peroxynitrite formation,
      arginase II expression, and eNOS down-regulation in the induction of a Peyronie's
      like condition in the rat.

PMID- 11330652
TI  - Testosterone effects on luteinizing hormone and follicle-stimulating hormone
      responses to gonadotropin-releasing hormone in the mouse.
AB  - Studies in the mouse have demonstrated for the first time in vivo regulation of
      gonadotropin-releasing hormone (GnRH) on the minute-to-minute dynamics of
      luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release and the
      effects of testosterone on this regulation. Intact and castrated mice with
      different testosterone levels (3-9 ng/mL) were challenged with exogenous GnRH
      while under general anesthesia to block endogenous GnRH release. Plasma
      concentrations of LH and FSH were determined by radioimmunoassay from sequential
      blood samples collected from anesthetized mice with in-dwelling catheters. The
      release of LH was correlated with the infusion of different doses of GnRH (0.35,
      3.5, and 35 ng) in both intact and castrated mice (r = 0.942, approximately
      0.999). GnRH-stimulated LH release was significantly lower in intact mice and in
      castrated mice with high testosterone levels than in castrated mice with low
      testosterone levels (P < .05). However, GnRH did not induce FSH release except in
      castrated males with low testosterone levels and at the highest dose of GnRH. The
      profiles of FSH release in intact mice and castrated mice with the highest
      testosterone levels were significant lower than the other groups (P < .05). In
      conclusion, release of LH, but not FSH, was correlated with increasing dosages of
      GnRH (r = 0.970), and testosterone significantly suppressed GnRH-stimulated LH
      release in the mouse (P < .05).

PMID- 11330653
TI  - Should celecoxib be contraindicated in patients who are allergic to sulfonamides?
      Revisiting the meaning of 'sulfa' allergy.
AB  - Celecoxib, a selective cyclo-oxygenase-2 inhibitor, is a diaryl-substituted
      pyrazole derivative containing a sulfonamide substituent. Because of this
      structural component, celecoxib is contraindicated for use in patients who have
      demonstrated allergic reactions to sulfonamides. However, there is a lack of data
      demonstrating cross-reactivity among sulfonamide medications. A sulfonamide is
      any compound with an SO2NH2 moiety. The major difference between sulfonamide
      antimicrobials and other sulfonamide-containing medications such as furosemide,
      thiazide diuretics and celecoxib, is that sulfonamide antimicrobials contain an
      aromatic amine group at the N4 position. This allows for division of the
      sulfonamides into 2 groups: aromatic amines (i.e., sulfonamide antimicrobials)
      and nonaromatic amines. In addition, sulfonamide antimicrobials contain a
      substituted ring at the N1-position; this group is not found with nonaromatic
      amine-containing sulfonamides. Adverse reactions to sulfonamide antimicrobials
      include type I, or immunoglobulin (Ig) E-mediated reactions, hypersensitivity
      syndrome reactions, and severe skin reactions such as toxic epidermal necrolysis.
      The aromatic amine portion of the sulfonamide antimicrobial is considered to be
      critical in the development of latter 2 reactions. In susceptible individuals,
      the hydroxylamine metabolite is unable to be detoxified leading to a cascade of
      cytotoxic and immunological events that eventually results in the adverse
      reaction. Since celecoxib does not contain the aromatic amine, adverse reactions
      such as hypersensitivity syndrome reactions and toxic epidermal necrolysis would
      not be expected to occur at the same frequency as they do with sulfonamide
      antimicrobials. Similarly, for IgE-mediated reactions, the N1-substituent and not
      the sulphonamide moiety is important in determining specificity to antibodies.
      Celecoxib and other nonaromatic amine-containing sulfonamide medications do not
      contain the N1-substituent. Cross-reactivity among the various sulfonamide
      containing medications has also not been substantiated by published case reports.
      In fact, conflicting information exists in the literature. Reports showing lack
      of cross-reactivity balance the few case reports suggesting cross-reactivity.
      Cross-reactivity between sulfonamide medications should be based on scientific
      data, including chemistry, metabolism, immune responses and clinical data. Based
      on the current information, there is no documentation for cross-reactivity
      between sulfonamide antimicrobials and other sulfonamide medications, such as
      celecoxib.

PMID- 11330654
TI  - Demyelinating disease and hepatitis B vaccination: is there a link?
AB  - The recent decision by the French government to compensate 3 recipients of
      hepatitis B vaccine preceding the onset of multiple sclerosis presumes a possible
      causal link and brings into question the use of current rules of causality
      assessment. Available evidence does not support a causal link or is equivocal but
      the accuracy of current methods of vaccine surveillance should be urgently
      improved. Larger and longer randomised trials, updated summaries of evidence,
      linked databases, prospective vaccination registers, bar-coding of vaccines and
      standardisation of adverse event definitions are possible measures to address
      current problems.

PMID- 11330655
TI  - A risk-benefit assessment of sildenafil in the treatment of erectile dysfunction.
AB  - Sildenafil is an oral treatment for erectile dysfunction (ED). It acts as an
      inhibitor of 3',5'-cyclic guanosine monophosphate-phosphodiesterase type 5. An
      effective treatment for ED is required to produce an erectile response sufficient
      for satisfactory sexual performance. This has been documented for sildenafil in
      men with ED of differing aetiologies and baseline severity in various types of
      clinical trials. Sildenafil treatment is characterised by a good tolerability
      profile and low treatment digcontinuation rate caused by treatment-related
      adverse effects. Most of the adverse effects associated with sildenafil are
      extensions of the pharmacological action of the drug. There is no significant
      difference in the adverse effect profile (headache, flushing, dyspepsia, nasal
      congestion and abnormal vision) of this agent as assessed by clinical data
      obtained either in the pre- and postlaunch periods. Because of its acceptable
      risk-benefit ratio, sildenafil can be prescribed to a very large group of
      patients with ED. The reports of serious cardiovascular events associated with
      the use of sildenafil (including anecdotal reports of deaths) have been very
      thoroughly analysed. A number of studies have not shown any difference in the
      risk of serious cardiovascular events in sildenafil- and placebo-treated
      patients. However, when making a risk-benefit evaluation, certain subgroups of
      patients need to be considered separately. In particular, sildenafil is
      contraindicated in patients receiving nitrate therapy. In some other subgroups of
      patients, the risks and benefits of treatment need to be assessed on an
      individual basis and it is hoped that additional data will clarify any possible
      risks associated with sildenafil administration such patients. It is helpful to
      compare the risk-benefit profile of sildenafil with the characteristics of other
      oral drugs for ED. According to the preliminary data, apomorphine and
      phentolamine are possible future options for the treatment of ED; however, there
      needs to be further clinical evaluation of these agents. Initial data have shown
      that sildenafil can be successfully combined with intracavernosal injection in
      patients nonresponders to either therapy. In conclusion, favourable
      characteristics make sildenafil suitable for the first-line therapy for a
      substantial proportion of patients with ED.

PMID- 11330656
TI  - A risk-benefit assessment of pharmacological therapies for hirsutism.
AB  - In recent years, many new therapeutic regimens for hirsutism have been
      introduced. This has considerably enlarged the different choices of the physician
      but at the same time has produced considerable confusion and uncertainty as to
      what is the best possible therapy for the single patient or for the different
      pathologies of this condition. This review presents data on the characteristics,
      adverse effects and effective dosage for the more commonly used drugs for
      hirsutism. In most patients, low doses of antiandrogens (cyproterone acetate,
      flutamide or spironolactone) are used with few adverse effects and good results
      in terms of improvement of the hirsutism. Patients with severe hyperandrogenic
      hirsutism may require larger doses of antiandrogens. In only a few patients,
      therapy with agents that primarily reduce androgen secretion (mostly a
      gonadotropin releasing hormone agonist) is needed. In responsive patients,
      dexamethasone may be used at low doses (associated with an antiandrogen) to
      prolong the length of the remission. Finally, agents that inhibit 5alpha
      reductase activity (finasteride) may be used as alternative to low dose
      antiandrogen therapy but the results are often less satisfactory.

PMID- 11330658
TI  - Cloning, expression, and characterization of a family 52 beta-xylosidase gene
      (xysB) of a multiple-xylanase-producing bacterium, Aeromonas caviae ME-1.
AB  - A lambda phage genomic library of Aeromonas caviae ME-1, a multiple-xylanase
      producing bacterium, was screened for xylan degradation activities. We isolated
      one clone, B65, which had weak xylanase activity, by the DNS method, but gave no
      visible bands on zymogram assay using SDS-xylan-PAGE. Based on TLC analyses of
      enzymatic products and some glycosidase assays using p-nitrophenyl substrates, we
      established that pB65 encodes a beta-xylosidase gene. In the nucleotide sequence
      analysis, we found a 2190-bp open reading frame (ORF) named xysB. XysB protein is
      similar to some beta-xylosidases, which are categorized in the glycosyl hydrolase
      family 52. Another ORF (xyg), that showed similarity to the family 67 alpha
      glucuronidase, was also found downstream of the xysB gene. The xysB ORF and its
      promoter region were cloned into the pT7-Blue vector and the transformant cells
      had beta-xylosidase activity. The relative molecular mass were estimated to be 75
      kDa by SDS-PAGE and 159 kDa by gel filtration. These data showed that XysB has a
      dimeric structure of 80,697 Da subunits. This enzyme showed optimal activity at
      50 degrees C and pH 6.0. It was stable below 40 degrees C and pH 5-8. The Km and
      Vmax were calculated to be 0.34 mM and 33 nmol x min(-1) x microg(-1),
      respectively. This enzyme also showed transglycosylation activity against X3 and
      produced X4 and X5.

PMID- 11330659
TI  - Hepatic mitochondrial proteins in congenitally hyperammonemic spf mice: effect of
      acetyl-L-carnitine.
AB  - The sparse-fur (spf) mutant mouse has an X-linked deficiency of hepatic ornithine
      transcarbamylase (OTC), and develops hyperammonemia immediately after weaning and
      maintains it throughout its life span. We have studied the effects of acetyl-L
      carnitine (ALCAR) on the hepatic mitochondrial proteins of the chronically
      hyperammonemic spf mice. Two different age groups of mice were studied, the
      weanlings (3 weeks) and the adult mice (8 weeks). Our results indicate that in
      the mitochondrial matrix, the untreated chronic hyperammonemia induced a
      significant increase in the quantity of 54.4-kDa protein in spf adult mice. After
      ALCAR treatment, in spf adult mice, the quantities of the 54.4-kDa, 63.8-kDa, and
      129-kDa matrix proteins were significantly increased. In the mitochondrial inner
      membrane fraction of the spf weanling mice, a 53.5-kDa protein was significantly
      increased by ALCAR treatment. Our results show that: (a) chronic hyperammonemia
      has altered the mitochondrial matrix protein profile in spf mice, that (b) ALCAR
      has a modulating effect on various matrix and inner membrane proteins, and that
      (c) there was no effect of hyperammonemia or ALCAR treatment on the outer
      membrane proteins.

PMID- 11330660
TI  - Purification, characterization, and molecular cloning of a chitinase from the
      seeds of Benincasa hispida.
AB  - A chitinase was purified from the seeds of Benincasa hispida, a medicinal plant
      also called white gourd, and a member of the Cucurbitaceae family. Purification
      was done by using a procedure consisting of only two fractionation steps: an acid
      denaturation step followed by ion-exchange chromatography. The sequence of the N
      terminal forty amino acid residues was analyzed and the sequence indicated that
      the enzyme is a class III chitinase. The enzyme, which is a basic chitinase, is
      one of at least five chitinases detected in the seed extract of B. hispida. Like
      other class III chitinases, this enzyme also has lysozyme activity. A genomic
      clone of the gene encoding the enzyme was isolated and sequenced. The gene has
      the potential to encode a protein of 301 amino acid residues. The deduced amino
      acid sequence of the protein, as expected from the N-terminal amino acid
      sequence, shares high degrees of similarity with other class III chitinases.

PMID- 11330661
TI  - DNA synthesis and fragmentation in bacteroids during Astragalus sinicus root
      nodule development.
AB  - Histo- and cytochemical techniques were used to study the DNA replication and
      fragmentation patterns in bacteroids formed by Mesorhizobium huakuii subsp.
      rengei in nodules of Astragalus sinicus. DNA replication was detected by the
      incorporation of 5-bromo deoxy-uridine. Signals denoting DNA synthesis were
      observed in plant nuclei within the nodule meristem and in bacteroids near the
      meristem. The TUNEL (TdT-mediated dUTP nick-end labeling) assay was used to
      measure DNA fragmentation. In nutrient-depleted 1-mpi (month(s) post inoculation)
      nodule sections, some bacteroids were in vacuoles, and DNA fragmentation signals
      were observed only in such bacteroids. In contrast, 1-mpi nodule sections without
      nutrient depletion showed neither bacteroid localization in vacuoles nor DNA
      fragmentation signals. The bacteroid translocation into vacuoles upon nutrient
      starvation might results from autophagy of the plant. In 2-mpi nodule sections,
      bacteroids with DNA fragmentation signals appeared within the cytoplasm of some
      nodule cells in the senescence zone.

PMID- 11330662
TI  - Natto mucilage containing poly-gamma-glutamic acid increases soluble calcium in
      the rat small intestine.
AB  - We prepared natto (fermented soybeans) mucilage containing poly-gamma-glutamic
      acid (gamma-PGA) from commercial natto. The effect of natto mucilage on calcium
      (Ca) solubility in vitro and in vivo was investigated. Ca solubility in vitro
      increased with an increase in the amount of natto mucilage, due to inhibition of
      the formation of an insoluble complex of Ca with phosphate by natto mucilage.
      Rats were fed with 5 g of soybean protein isolate, natto, mucilage-free natto, or
      natto mucilage diet for 1.5 h. Small intestinal contents were collected 2.5 h
      after ingestion. In the lower half of the small intestine, both the amount and
      the percentage of soluble Ca of intestinal contents were significantly higher (P
      < 0.001) in rats fed with natto mucilage diet than in those fed with the other
      diets. Natto mucilage also increased Ca solubility in vivo. These results
      suggested that gamma-PGA is responsible for the increasing effect of natto
      mucilage on Ca solubility.

PMID- 11330663
TI  - Improving the freeze tolerance of bakers' yeast by loading with trehalose.
AB  - We examined the freeze tolerance of bakers' yeast loaded with exogenous
      trehalose. Freeze-tolerant and freeze-sensitive compressed bakers' yeast samples
      were soaked at several temperatures in 0.5 M and 1 M trehalose and analyzed. The
      intracellular trehalose contents in both types of bakers' yeast increased with
      increasing soaking period. The initial trehalose-accumulation rate increased with
      increasing exogenous trehalose concentration and soaking temperature. The maximum
      trehalose content was almost identical (200-250 mg/g of dry cells) irrespective
      of the soaking temperature and the type of bakers' yeast, but depended on the
      exogenous trehalose concentration. The leavening ability of both types of bakers'
      yeast loaded with trehalose was almost identical to that of the respective
      original cells, irrespective of the soaking conditions. The freeze-tolerant ratio
      (FTR) of both types of bakers' yeast increased with increasing intracellular
      trehalose content. However, FTR decreased during over-soaking after the maximum
      amount of trehalose had accumulated. FTR of the freeze-sensitive bakers' yeast
      was more efficiently improved than that of the freeze-tolerant type.

PMID- 11330664
TI  - Purification and characterization of an beta-D-xylosidase from Candida utilis IFO
      0639.
AB  - An intracellular beta-D-xylosidase from Candida utilis IFO 0639 was purified to
      homogeneity through four chromatographic steps. The molecular mass of the enzyme
      was estimated to be 92 kDa by SDS-PAGE. The enzyme had an isoelectric point at
      5.6, and was most active at pH 6.0 and at around 40 degrees C. Ethanol at an
      optimal concentration (10%, v/v) stimulated the initial enzyme activity by 57%. D
      Xylose, the product of the beta-D-xylosidase, has no effect on the enzyme
      activity at 300 mM. The beta-D-xylosidase was highly specific to the beta-D
      xylopyranoside configuration. The enzyme hydrolyzed beta-1,4-linked xylo
      oligosaccharides with chain lengths from 2 to 5 by releasing xylose from the non
      reducing end. It showed no activity against xylan. The enzyme efficiently
      released monoterpenols from an aroma precursor extracted from Muscat grape juice.
      The fermentation of Muscat juice coupled with the enzyme addition produced a
      small increase in the concentration of monoterpenols.

PMID- 11330657
TI  - Risks and benefits of nicotine to aid smoking cessation in pregnancy.
AB  - Cigarette smoking during pregnancy is the single largest modifiable risk for
      pregnancy-related morbidity and mortality in the US. Addiction to nicotine
      prevents many pregnant women who wish to quit smoking from doing so. The safety
      and efficacy of nicotine replacement therapy (NRT) for smoking cessation during
      pregnancy have not been well studied. Nicotine is classified by the US Food and
      Drug Administration as a Pregnancy Category D drug. Animal studies indicate that
      nicotine adversely affects the developing fetal CNS, and nicotine effects on the
      brain may be involved in the pathophysiology of sudden infant death syndrome
      (SIDS). It has been assumed that the cardiovascular effects of nicotine resulting
      in reduced blood flow to the placenta (uteroplacental insufficiency) is the
      predominant mechanism of the reproductive toxicity of cigarette smoking during
      pregnancy. Short term high doses of nicotine in pregnant animals do adversely
      affect the maternal and fetal cardiovascular systems. However, studies of the
      acute effects of NRT in pregnant humans indicate that nicotine alone has minimal
      effects upon the maternal and fetal cardiovascular systems. Cigarette smoking
      delivers thousands of chemicals, some of which are well documented reproductive
      toxins (e.g. carbon monoxide and lead). A myriad of cellular and molecular
      biological abnormalities have been documented in placentas, fetuses, and newborns
      of pregnant women who smoke. The cumulative abnormalities produced by the various
      toxins in cigarette smoke are probably responsible for the numerous adverse
      reproductive outcomes associated with smoking. It is doubtful that the
      reproductive toxicity of cigarette smoking is primarily related to nicotine. We
      recommend the following. Efficacy trials of NRT as adjunctive therapy for smoking
      cessation during pregnancy should be conducted. The initial dose of nicotine in
      NRT should be similar to the dose of nicotine that the pregnant woman received
      from smoking. Intermittent-use formulations of NRT (gum, spray, inhaler) are
      preferred because the total dose of nicotine delivered to the fetus will be less
      than with continuous-use formulations (transdermal patch). A national registry
      for NRT use during pregnancy should be created to prospectively collect
      obstetrical outcome data from NRT efficacy trials and from individual use. The
      goal of this registry would be to determine the safety of NRT use during
      pregnancy, especially with respect to uncommon outcomes such as placental
      abruption. Finally, our review of the data indicate that minimal amounts of
      nicotine are excreted into breast milk and that NRT can be safely used by breast
      feeding mothers.

PMID- 11330665
TI  - Involvement of caspase-3 in apoptosis induced by Viscum album var. coloratum
      agglutinin in HL-60 cells.
AB  - A cytotoxic lectin (Viscum album L. coloratum agglutinin, VCA) from Korean
      mistletoe was isolated by affinity chromatography on Sepharose 4B immobilized
      with asialofetuin. In HL-60 cells, addition of VCA resulted in a dose- and time
      dependent growth suppression, morphological changes of apoptotic nuclei, and DNA
      fragmentation characteristics of apoptosis. To investigate how caspase-3
      activation during VCA-induced apoptosis induces cleavages of PARP, the expression
      of PARP and the pattern of caspase-3 activation in HL-60 cells were investigated.
      The native and processed PARP forms typically seen in apoptotic cells were
      observed, and a decrease in expression of the 32-kDa form of caspase-3 in a dose
      dependent manner was observed. The VCA-induced apoptosis was significantly
      inhibited by a caspase-3 specific inhibitor, z-DEVD-FMK, and the PARP processing
      and caspase-3 activation were also inhibited by the inhibitor. A possible
      involvement of cell cycle arrest in VCA-induced apoptosis was investigated by
      flow cytometry and the results suggested that the apoptotic effect of VCA is not
      involved in the induction of cell cycle arrest.

PMID- 11330667
TI  - Sequence of the Clostridium thermocellum mannanase gene man26B and
      characterization of the translated product.
AB  - The man26B gene of Clostridium thermocellum strain F1 was found in pKS305, which
      had been selected as a recombinant plasmid conferring endoglucanase activity on
      Escherichia coli. The open reading frame of man26B consists of 1,773 nucleotides
      encoding a protein of 591 amino acids with a predicted molecular weight of
      67,047. Man26B is a modular enzyme composed of an N-terminal signal peptide and
      three domains in the following order: a mannan-binding domain, a family 26
      mannanase domain, and a dockerin domain responsible for cellulosome assembly. We
      found that this gene was a homologue of the man26A gene of C. thermocellum strain
      YS but that there were insertion or deletion mutations that caused a frame-shift
      mutation affecting a stretch of 26 amino acids in the catalytic domain. Man26B
      devoid of the dockerin domain was constructed and purified from a recombinant E.
      coli, and its enzyme properties were examined. Immunological analysis indicated
      that Man26B was a catalytic component of the C. thermocellum F1 cellulosome.

PMID- 11330666
TI  - Inhibitory effects of ellagi- and gallotannins on rat intestinal alpha
      glucosidase complexes.
AB  - The clove ellagitannins and their related polygalloyl-glucoses inhibited maltase
      activity of rat intestinal alpha-glucosidases. The structure-activity
      relationship study of those galloylglucoses, varying the extent of galloylation
      on the glucose core, with the ellagitannins, indicated that an increasing number
      of galloyl units in the molecule lead to an increase in the inhibitory activity.
      Penta-O-galloyl-beta-D-glucose, with five galloyl groups showed the highest
      inhibitory activity. On the other hand, hexahydroxydiphenoyl units contained in
      the ellagitannins had little effect on the activity. After separation of maltase
      glucoamylase and sucrase-isomaltase complexes from the crude mixture of the rat
      alpha-glucosidases, the inhibitory activities of the galloylglucose derivatives
      against each complex were examined. The inhibitory influence on the maltase
      glucoamylase complex was more potent than on the sucrase-isomaltase complex.

PMID- 11330668
TI  - Mechanism of growth inhibition by tungsten in Acidithiobacillus ferrooxidans.
AB  - Cell growth of three hundred iron-oxidizing bacteria isolated from natural
      environments was inhibited strongly by 0.05 mM, and completely by 0.2 mM of
      sodium tungstate (Na2WO4), respectively. Since no great difference in the level
      of tungsten inhibition was observed among the 300 strains tested, the mechanism
      of inhibition by Na2WO4 was studied with Acidithiobacillus ferrooxidans strain
      AP19-3. When resting cells of AP19-3 were incubated in 0.1 M beta-alanine-SO4(2-)
      buffer (pH 3.0) with 0.1 mM Na2WO4 for 1 h, the amount of tungsten bound to the
      cells was 12 microg/mg protein. The optimum pH for tungsten binding to the
      resting cells was 2 to approximately 3. Approximately 2 times more tungsten bound
      to the cells at pH 3.0 than at pH 6.0. The tungsten binding was specifically
      inhibited by sodium molybdenum. However, copper, nickel, cadmium, zinc,
      manganese, cobalt, and vanadate did not disturb tungsten binding to the resting
      cells. The iron-oxidizing activity of AP19-3 was inhibited 24, 62, and 77% by 1,
      5, and 10 mM of Na2WO4, respectively. Among the components of iron oxidation
      enzyme system, iron:cytochrome c oxidoreductase activity was not inhibited by 10
      mM of Na2WO4. In contrast, the activity of cytochrome c oxidase purified highly
      from the strain was inhibited 50 and 72%, respectively, by 0.05 and 0.1 mM of
      Na2WO4. The amounts of tungsten bound to plasma membrane, cytosol fraction, and a
      purified cytochrome c oxidase were 8, 0.5, and 191 microg/mg protein,
      respectively. From the results, the growth inhibition by Na2WO4 observed in A.
      ferrooxidans is explained as follows: tungsten binds to cytochrome c oxidase in
      plasma membranes and inhibits cytochrome c oxidase activity, and as a results,
      the generation of energy needed for cell growth from the oxidation of Fe2+ is
      stopped.

PMID- 11330669
TI  - Cloning and expression of cDNA encoding the complete prepro-form of an isoform of
      Der f 1, the major group 1 allergen from house dust mite Dermatophagoides
      farinae.
AB  - cDNA clones encoding a major house dust mite allergen, Der f 1, were isolated
      from a Dermatophagoides farinae cDNA library by plaque immunoscreening using
      rabbit anti-Der f 1 serum. The sequences cover the complete open reading frame
      encoding the prepro-form. The sequence is different from previously reported cDNA
      of Der f 1 in six bases and the encoded amino acid sequence is different in two
      residues. Pro-forms of Der f 1 and its mutant, in which the N-glycosylation motif
      was disrupted, expressed in Pichia pastoris were converted to the mature forms by
      an in vitro activation process and they showed significant IgE-binding. The
      biologically active rDer f 1 molecules would be useful for diagnostic testing and
      allergen-specific immunotherapy. In contrast, Der f 1 directly expressed in
      Escherichia coli without the prosequence had very low IgE binding. The
      hypoallergenic Der f 1 polypeptide could be useful for safer and more effective
      immunotherapy.

PMID- 11330670
TI  - Investigation of various genotype characteristics for inosine accumulation in
      Escherichia coli W3110.
AB  - For the derivation of an inosine-overproducing strain from the wild type
      microorganism, it is known that the addition of an adenine requirement, removal
      of purine nucleoside hydrolyzing activity, removal of the feedback inhibition,
      and repression of key enzymes in the purine nucleotides biosynthetic pathway are
      essential. Thus, the disruption of purA (adenine requirement), deoD (removal of
      purine nucleosides phosphorylase activity), purR (derepression of the regulation
      of purine nucleotides biosynthetic pathway), and the insensitivity of the
      feedback inhibition of phosphoribosylpyrophosphate (PRPP) amidotransferase by
      adenosine 5'-monophosphate (AMP) and guanosine 5'-monophosphate (GMP) were done
      in the Escherichia coli strain W3110, and then the inosine productivity was
      estimated. In the case of using a plasmid harboring the PRPP amidotransferase
      gene (purF) that encoded a desensitized PRPP amidotransferase, purF disrupted
      mutants were used as the host strains. It was found that the innovation of the
      four genotypes brought about a small amount of inosine accumulation. Furthermore,
      an adenine auxotrophic mutant of E. coli showed inappropriate adenine use because
      its growth could not respond efficiently to the concentration of adenine added.
      As the presence of adenosine deaminase is well known in E. coli and it is thought
      to be involved in adenine use, a mutant disrupted adenosine deaminase gene (add)
      was constructed and tested. The mutant, which is deficient in purF, purA, deoD,
      purR, and add genes, and harboring the desensitized purF as a plasmid,
      accumulated about 1 g of inosine per liter. Although we investigated the effects
      of purR disruption and purF gene improvement, unexpectedly an increase in the
      inosine productivity could not be found with this mutant.

PMID- 11330671
TI  - Green marker for colonies of Bacillus subtilis.
AB  - A Bacillus subtilis plasmid encoding a green fluorescence protein gene (gfp) was
      constructed. The fluorescence of B. subtilis colonies having this plasmid on agar
      plates was so high that they could be readily discerned visually under UV light.
      The fluorescence could be effectively expressed in three ways (i) through use of
      a strong bsr promoter (blasticidin S resistance gene), (ii) by efficient
      translation with the bsr translation system, and (iii) through increase in the
      copy number per cell. The high stability of the GFP plasmid was demonstrated by
      using more complicated growth conditions without any antibiotic for selection.

PMID- 11330672
TI  - Purification and characterization of goose type lysozyme from cassowary
      (Casuarius casuarius) egg white.
AB  - A novel goose-type lysozyme was purified from egg white of cassowary bird
      (Casuarius casuarius). The purification step was composed of two fractionation
      steps: pH treatment steps followed by a cation exchange column chromatography.
      The molecular mass of the purified enzyme was estimated to be 20.8 kDa by SDS
      PAGE. This enzyme was composed of 186 amino acid residues and showed similar
      amino acid composition to reported goose-type lysozymes. The N-terminal amino
      acid sequencing from transblotted protein found that this protein had no N
      terminal. This enzyme showed either lytic or chitinase activities and had some
      different properties from those reported for goose lysozyme. The optimum pH and
      temperature on lytic activity of this lysozyme were pH 5 and 30 degrees C at
      ionic strength of 0.1, respectively. This lysozyme was stable up to 30 degrees C
      for lytic activity and the activity was completely abolished at 80 degrees C. The
      chitinase activity against glycol chitin showed dual optimum pH around 4.5 and
      11. The optimum temperature for chitinase activity was at 50 degrees C and the
      enzyme was stable up to 40 degrees C.

PMID- 11330673
TI  - Oxidative stress by visible light irradiation suppresses immunoglobulin
      production in mouse spleen lymphocytes.
AB  - In this study, we attempted to induce the oxidative stress in mouse spleen
      lymphocytes with visible light irradiation and examined the effects of lipid
      peroxidation on immunoglobulin (Ig) production. The spleen lymphocytes were
      isolated from 8-week-old male balb/c mice and irradiated with 300 W visible
      light. When the cells were cultured for 72 hr, Ig contents in culture
      supernatants were decreased gradually by irradiation for over 30 min. The cell
      viability was also lowered by the irradiation. Intracellular phosphatidylcholine
      hydroperoxide (PCOOH) levels and thiobarbituric acid-reactive substances (TBARS)
      values in culture supernatants were measured as indices of lipid peroxidation and
      we found that Ig production by mouse spleen lymphocytes was suppressed
      accompanied with the progress of peroxidation of intracellular phospholipids.
      Cell membrane fluidity was also significantly decreased, but the intracellular Ig
      level was not changed in the irradiated cells. These results suggest that the
      peroxidation of intracellular lipids is a cause of the suppression of Ig
      production by mouse spleen lymphocytes via lowering cell viability and
      suppressing Ig synthesis and secretion.

PMID- 11330674
TI  - Effects of 2,3-diketo-L-gulonic acid on the oxidation of yolk lipoprotein.
AB  - 2,3-Diketo-L-gulonic acid (DKG) is an important intermediate product of oxidative
      degradation of L-ascorbic acid (AsA) in both biological and food systems, but the
      physiological function of DKG is still unclear. In this study, it was found that
      DKG had a strong antioxidative effect on copper-dependent oxidative modification
      of yolk lipoprotein (YLP), on the basis of both the decreased electrophoretic
      mobility and longer lag time of conjugated diene formation in a concentration
      dependent manner. DKG is known to be very unstable and easily converts into two
      delta-lactones of DKG, the 3,4-enediol form of DKG delta-lactone (3,4-DKGL) and
      2,3-enediol form of DKG delta-lactone (2,3-DKGL) depending on both pH and
      temperature. 3,4-DKGL was thought to be the first degradation product of DKG and
      could play an antioxidative role in the oxidation of lipoproteins induced by
      copper ion or peroxyl radicals in neutral aqueous solution.

PMID- 11330675
TI  - Expression pattern of the CsPK3 auxin-responsive protein kinase gene.
AB  - We have previously cloned a cDNA of a putative serine/threonine protein kinase
      gene named CsPK3 from cucumber, the mRNA level of which was up-regulated by auxin
      and down-regulated by light irradiation. To examine the CsPK3 gene expression in
      detail, we cloned a genomic DNA of CsPK3 gene and made transgenic tobacco
      (Nicotiana tabacum L. cv. Petit Havana SR1) plants containing the fused CsPK3
      promoter-beta-glucuronidase gene. The beta-glucuronidase expression was detected
      in the shoot apex, vascular tissues, and the outermost layer of cortex. The
      histological distribution of CsPK3 mRNA in cucumber seedlings was supported by in
      situ hybridization, where the positive signals were observed in similar tissues
      as those observed by beta-glucuronidase staining. The responsiveness of the CsPK3
      gene to auxin and light was also confirmed for beta-glucuronidase activity. The
      pattern of beta-glucuronidase staining changed during the development of the
      tobacco seedlings. The results of our experiment showed that CsPK3 was expressed
      in a wide variety of tissues and cells in which the developmental and growth
      controls by auxin are suggested.

PMID- 11330676
TI  - Improving effect of feeding with a phosphorylated guar gum hydrolysate on calcium
      absorption impaired by ovariectomy in rats.
AB  - We have previously reported that a phosphorylated guar gum hydrolysate (P-GGH)
      promoted calcium absorption and the accumulation of bone calcium in rats. We now
      investigate the effect of P-GGH (50 g/kg of diet) on the intestinal calcium
      absorption and bones of ovariectomized (OVX) rats in comparison with sham
      operated rats over a six-week ingestion period. The apparent calcium absorption
      was decreased by aging and ovariectomy in the rats fed on the control and GGH
      diets (50 g/kg of diet), but not in the rats fed on the P-GGH diet. The
      absorption was higher in the P-GGH group than in the GGH and control diet groups
      in the fourth and sixth weeks after feeding the test diets to OVX rats. Femoral
      calcium and strength were decreased by OVX in the rats fed on the control and GGH
      diets, but not in the rats fed on the P-GGH diet. The values of these parameters
      were higher in the P-GGH group than in either the control or GGH group of OVX
      rats. The amount of soluble calcium in the ileal contents was higher in the P-GGH
      group than in the control and GGH groups. These results indicate that P-GGH may
      be useful for preventing the reduction of intestinal calcium absorption and bone
      in the condition of estrogen deficiency.

PMID- 11330677
TI  - Structures of Thermoactinomyces vulgaris R-47 alpha-amylase II complexed with
      substrate analogues.
AB  - The structures of Thermoactinomyces vulgaris R-47 alpha-amylase II mutant
      (d325nTVA II) complexed with substrate analogues, methyl beta-cyclodextrin (m
      beta-CD) and maltohexaose (G6), were solved by X-ray diffraction at 3.2 A and 3.3
      A resolution, respectively. In d325nTVA II-m beta-CD complex, the orientation and
      binding-position of beta-CD in TVA II were identical to those in cyclodextin
      glucanotransferase (CGTase). The active site residues were essentialy conserved,
      while there are no residues corresponding to Tyr89, Phe183, and His233 of CGTase
      in TVA II. In d325nTVA II-G6 complex, the electron density maps of two glucosyl
      units at the non-reducing end were disordered and invisible. The four glucosyl
      units of G6 were bound to TVA II as in CGTase, while the others were not stacked
      and were probably flexible. The residues of TVA II corresponding to Tyr89,
      Lys232, and His233 of CGTase were completely lacking. These results suggest that
      the lack of the residues related to alpha-glucan and CD-stacking causes the
      functional distinctions between CGTase and TVA II.

PMID- 11330678
TI  - Characterization and high-level production of D-amino acid oxidase in Candida
      boidinii.
AB  - D-Amino acid oxidase (DAO, EC 1.4.3.3) from a methylotrophic yeast, Candida
      boidinii, was produced at a high level under the control of the alcohol oxidase
      gene promoter in the original host. The enzyme was a peroxisomal and monomeric
      enzyme, and contained noncovalently-bound FAD as a cofactor. The enzyme was
      active toward several D-amino acids such as D-Ala, D-Met, and D-Ser. An alcohol
      oxidase-depleted strain (aod1delta) was found to be a more suitable host for DAO
      production than the wild-type strain. Several post-translational effects may be
      responsible for the improvement of the DAO productivity by the aod1delta strain.
      Finally, an aod1delta strain transformant having multi-copies of an expression
      plasmid on its chromosome could produce DAO amounting up to 30% of the total
      soluble proteins.

PMID- 11330679
TI  - Resolution and synthesis of optically active alcohols with immobilized ovalbumin
      and pea protein as new bio-catalysts.
AB  - It was found that ovalbumin stereoselectively oxidized one of the enantiomers of
      p-substituted racemic alcohols, thereby providing optically active alcohols with
      high optical purities. It was found out that, when used appropriately in
      combination with immobilized pea protein, immobilized ovalbumin made it possible
      to resolve and synthesize racemic 1-(2-naphthyl)ethanol, 1-phenylethanol, and 1
      phenyl-1-propanol. Immobilized ovalbumin could be continuously recycled at least
      three times without lowering the yield and purity of the products. These results
      suggested that cereals, beans, and ovalbumin might have additional fourth
      function among conventional foods. Namely, there might contain nutritional,
      sensory, biologically regulatory and bio-catalytic functions in conventional
      foods.

PMID- 11330680
TI  - Capsaicin increases modulation of sympathetic nerve activity in rats: measurement
      using power spectral analysis of heart rate fluctuations.
AB  - We assessed the sympatho-vagal activities of the heart after administration of
      capsaicin by measuring the power spectral analysis in rats. There were major two
      frequency components of heart rate variability, which we defined as high (1.0 Hz
      <, HF) and low (LF, < 1.0 Hz) frequency components. Vagal blockade by atropine
      abolished the high frequency component, and lowered the amplitude of the low
      frequency component. On the other hand, under conditions of sympathetic blockade
      by propranolol, the low frequency component was reduced. Combined vagal and
      sympathetic blockade abolished all heart rate fluctuations. We analyzed the low
      and high frequency components by integrating the spectrum for the respective band
      width. The rats administered capsaicin had a higher heart rate and sympathetic
      nervous system index (LF/HF) than the control group of rats. These results
      suggest that power spectral analysis is an effective and noninvasive method for
      detecting subtle changes in autonomic activity in response to the intake of foods
      or drugs.

PMID- 11330681
TI  - ATP production from adenine by a self-coupling enzymatic process: high-level
      accumulation under ammonium-limited conditions.
AB  - To improve ATP production from adenine, we optimized cultivation and reaction
      conditions for the ATP producing strain, Corynebacterium ammoniagenes KY13510. In
      the conventional method, 28% NH4OH has been used both to adjust pH during
      cultivation and reaction, and to provide nitrogen for cell growth. In the ATP
      producing reaction, high concentrations of inorganic phosphate and magnesium ion
      are needed, which form magnesium ammonium phosphate (MgNH4PO4) precipitate. To
      keep inorganic phosphate and magnesium ions soluble in the reaction mixture, it
      was indispensable to add phytic acid as a chelating agent of divalent metal ions.
      Under such conditions, 37 mg/ml (61.2 mM) ATP was accumulated in 13 h (Appl.
      Microbiol. Biotechnol. 21, 143 1985). If ammonium ion was depleted from the
      reaction mixture to avoid MgNH4 PO4 formation, we expected that there was no need
      to add phytic acid and ATP accumulation might be improved. Therefore, we obtained
      the cultured broth of C. ammoniagenes KY13510 strain with low ammonium ion
      content (less than 1 mg/ml as NH3) by the method that a part of alkali solution
      (28% NH4OH) for pH control was replaced with 10 N KOH. Using this culture broth,
      ATP producing reaction was done in 2-liter jar fermentor, controlling the pH of
      the reaction mixture with 10 N KOH. Under these conditions, the rate of ATP
      accumulation improved greatly, and 70.6 mg/ml (117 mM) ATP was accumulated in 28
      h. The molar conversion ratio from adenine to ATP was about 82%. Phytic acid was
      slightly inhibitory to ATP formation under these ammonium-limited conditions.

PMID- 11330682
TI  - Inhibition of telomerase activity by fungus metabolites, CRM646-A and thielavin
      B.
AB  - We performed a screening program to identify telomerase inhibitors from our drug
      source obtained from fungus fermentations, and found that two compounds, CRM646-A
      and thielavin B, inhibited telomerase activity at doses of 3.2 and 32 microM,
      respectively. These compounds also inhibited the activity of viral reverse
      transcriptase at almost the same dose levels which inhibited telomerase activity.

PMID- 11330683
TI  - Isolation and characterizartion of alginic acid from commercially cultured
      Nemacystus decipiens (Itomozuku).
AB  - An alginate was isolated from commercially cultured Nemacystus decipiens which
      had been harvested in Yonashiro Town (Okinawa, Japan). The yield of the alginate
      was 1.6% (w/w of wet alga), and the uronic acid, ash and moisture contents of the
      alginate were 86.0%, 12.0%, and 2.3% (w/w), respectively. The molecular mass of
      the alginate was estimated to be about 1.5 x 10(5). The infrared spectrum and
      optical rotation of the alginate were in agreement with those of the standard
      alginate. D-Mannuronic acid and L-guluronic acid were identified by 1H- and 13C
      NMR spectroscopy, the molar ratio of both sugar residues being estimated to be
      0.72:1.00.

PMID- 11330684
TI  - Purification and characterization of mannose isomerase from Agrobacterium
      radiobacter M-1.
AB  - A mannose isomerase from Agrobacterium radiobacter M-1 (formerly Pseudomonas sp.
      MI) was purified to electrophoretic homogeneity and characterized. A cell-free
      extract was separated by ammonium sulfate fractionation, Butyl-Toyopearl 650M,
      DEAE-Sepharose and hydroxylapatite column chromatography. Its molecular mass was
      estimated to be 44 kDa by SDS-PAGE and 90 kDa by gel filtration, in which the
      enzyme is most likely a dimer composed of two identical subunits. The purified
      enzyme had an optimum pH at 8.0, an optimum temperature at 60 degrees C, a pI of
      5.2 and a Km of 20 mM, and specifically converted D-mannose and D-lyxose to
      ketose. The N-terminal amino acid sequence was identified.

PMID- 11330685
TI  - Polymorphism in rice amylases at an early stage of seed germination.
AB  - A polymorphism in rice amylases at an early stage of seed germination is analyzed
      by zymogram. In non-glutinous cultivars of rice, alpha-amylase isozymes are
      mainly confirmed in germinating seeds. However, in glutinous cultivars, beta
      amylase isozymes, which are not confirmed in nonglutinous cultivars, make up the
      major part of the total amylase activity and the expression of alpha-amylases are
      repressed.

PMID- 11330686
TI  - Characterization of the gene encoding the beta-lactamase of the psychrophilic
      marine bacterium Moritella marina strain MP-1.
AB  - The beta-lactamase gene (mbla) of the psychrophilic marine bacterium Moritella
      marina strain MP-1 was identified in a previously isolated genomic DNA fragment
      and it was expressed in Escherichia coli cells. The mbla gene encoded a protein
      consisting of 287 amino acid residues. Its predicted amino acid sequence showed
      approximately 50% identity with that of a number of class A beta-lactamases,
      especially with that of CARB/PSE type of beta-lactamases (carbenicillinases). E.
      coli transformed with the plasmid containing mbla grew on an ampicillin
      containing plate at 37 degrees C but not at 42 degrees C, suggesting that the
      beta-lactamase of this bacterium is heat-labile.

PMID- 11330687
TI  - Suppression of lipopolysaccharide-induced liver injury by various types of tea
      and coffee in D-galactosamine-sensitized rats.
AB  - Extracts of various types of tea and coffee significantly suppressed
      lipopolysaccharide (LPS)-induced liver injury, as assessed by the plasma enzyme
      activities, in D-galactosamine-sensitized rats when administered orally once
      before injecting the drugs. There was a significant negative correlation between
      the caffeine levels of these extracts and liver injury. Authentic caffeine also
      had a hepatoprotective effect. These results suggest that caffeine-containing
      beverages generally suppress LPS-induced liver injury according to their caffeine
      content.

PMID- 11330688
TI  - Suppressive effect of caffeine on hepatitis and apoptosis induced by tumor
      necrosis factor-alpha, but not by the anti-Fas antibody, in mice.
AB  - Tumor necrosis factor (TNF)-alpha-induced hepatitis and apoptosis, as
      respectively assessed by serum enzyme activities and hepatic DNA fragmentation
      were effectively suppressed by a single force-feeding of caffeine (100 mg/kg) 1.5
      h before injecting the drug. In contrast, caffeine had no significant effect on
      anti-Fas antibody-induced hepatitis and apoptosis. These results suggest that
      caffeine differentially affected TNF-alpha receptor- and Fas-mediated hepatitis
      and apoptosis.

PMID- 11330689
TI  - Molecular cloning of three genes encoding G protein alpha subunits in the white
      root rot fungus, Rosellinia necatrix.
AB  - Three genes encoding G protein alpha subunits were cloned from the white root rot
      fungus, Rosellinia necatrix, and characterized. Only one copy of each gene was
      present in the genome. The protein sequences of Rga1, Rga2, and Rga3 are very
      similar to those of MagA, MagB and MagC of Magnaporthe grisea, respectively.
      Moreover, Rga1 is similar to Mod-D which is closely related to vegetative
      incompatibility in Podospora anserina, which suggests that Rga1 is important in
      the vegetative incompatibility reaction in R. necatrix. Reverse transcription PCR
      (RT-PCR) analysis of Rga1, Rga2, and Rga3 mRNA expression showed that the three
      genes were all transcribed in R. necatrix cells.

PMID- 11330690
TI  - Antiviral activity of fattiviracin FV-8 against human immunodeficiency virus type
      1 (HIV-1).
AB  - A novel antiviral agent, fattiviracin FV-8, purified from the culture broth of
      Streptomyces microflavus strain No. 2445, showed potent antiviral activities
      against human immunodeficiency virus type 1 (HIV-1), herpes simplex virus type 1
      (HSV-1), varicella-zoster virus (VZV), and influenza A and B viruses. The action
      mechanism of fattiviracin FV-8 against HIV-1 was examined. As a result, the agent
      was thought to act on HIV-1 particles directly without lysis of the particles,
      and it affords the inhibition of viral entry into the host cells.

PMID- 11330691
TI  - A lectin from an ascomycete mushroom, Melastiza chateri: no synthesis of the
      lectin in mycelial isolate.
AB  - Using an affinity adsorbent prepared from L-fucose and starch, a lectin was
      isolated from fruit bodies of an ascomycete mushroom, Melastiza chateri. The
      lectin was found to cross-react with antiserum against Aleuria aurantia lectin
      (AAL), that had been obtained from another ascomycete mushroom. The N-terminal
      amino acid sequence was analyzed, and among 20 residues 12 were the same as AAL.
      The molecular mass of the lectin estimated by SDS-PAGE was approximately 40 kDa,
      which is larger than that of AAL. Mycelial isolate was obtained from M. chateri
      by germinating ascospores, and identified by analyzing restriction fragment
      length polymorphisms (RFLP) of DNA. The isolate from M. chateri did not
      synthesize the lectin, although the isolate from A. aurantia had been known to
      synthesize AAL as much as the fruit body.

PMID- 11330692
TI  - Piezoresponse of the cyo-operon coding for quinol oxidase subunits in a deep-sea
      piezophilic bacterium, Shewanella violacea.
AB  - We have isolated the genes for quinol oxidase from a deep-sea piezophilic
      bacterium, Shewanella violacea. Analysis of the deduced amino acid sequences of
      the cyo subunits showed that this oxidase has high similarity to Escherichia coli
      bo-type quinol oxidase. Northern blot analysis showed that these genes are
      expressed at a high level when the bacterium is grown at elevated pressure.
      Upstream in the cyo-operon, a sigma54-binding motif and an octamer sequence unit
      were found, suggesting that these elements may play a role in regulation of
      expression of the cyo-operon in response to changes in pressure.

PMID- 11330693
TI  - Reactivities of mutants of a major house dust mite allergen Der f 2 to mouse anti
      Der f 2 monoclonal antibodies analyzed by immunoblotting.
AB  - A total of sixteen recombinant variants of a major house dust mite allergen Der f
      2, the wild-type Der f 2, six cysteine mutants, six proline mutants, and three
      lysine mutants, were expressed in Escherichia coli. The cells were solubilized
      and run on SDS-PAGE under reducing conditions. Epitopes for five mouse anti-Der f
      2 monoclonal antibodies, 1B2, 7C10, 13A4, 15E11, and 18G8, to the recombinant Der
      f 2 variants were characterized by immunoblot analysis.

PMID- 11330694
TI  - Thermally induced changes of lipoate acetyltransferase inner core isolated from
      the Bacillus stearothermophilus pyruvate dehydrogenase complex.
AB  - Incubation at 70 degrees C converted the Bacillus stearothermophilus lipoate
      acetyltransferase inner core into an unidentified active molecular form, X,
      yielding an inactive aggregate. The core and X showed similar thermostabilities,
      but they were different in the recovery of enzyme activity after incubation with
      1.2-2.0 M guanidine hydrochloride and its subsequent removal; the core was hardly
      recovered, but X was well recovered.

PMID- 11330696
TI  - Chemical and nutritional properties of hypoallergenic wheat flour.
AB  - The chemical and nutritional properties were investigated of hypoallergenic wheat
      flour (HWF) prepared by the cellulase-actinase treatment. HWF was composed mainly
      of oligopeptides and free amino acids, and its average molecular weight was lower
      than 1,000. Feeding tests on rats showed that, with respect to the PER, GOT and
      GPT activities and other nutritional indices, the HWF diet was almost equivalent
      to the control diet which had been prepared from normal wheat flour (NWF). No
      abnormality was apparent in the main organs after the HWF diet had been fed for 3
      weeks. The small intestinal absorption of the HWF diet was found normal by
      measuring the free amino acid concentration in the intestinal tract and in the
      portal vein plasma. These data suggest that the absorption of amino acids from
      the HWF diet was comparable with or more efficient than that from a simulated
      free amino acid diet.

PMID- 11330695
TI  - Autoproteolytic processing of aspartic proteinase from sunflower seeds.
AB  - The autoproteolytic processing of mature aspartic proteinase from sunflower seeds
      was investigated. The mature aspartic proteinase (48 kDa) was processed at N65s
      D66s in the plant-specific region of the enzyme to form 34-kDa and 14-kDa
      subunits. The next step was the hydrolysis of the A25s-Q26s and N97s-E98s bonds
      to form a 39-kDa enzyme that consisted of 29-kDa and 9-kDa disulfide-bonded
      subunits. Finally, bonds including V1s-M2s, M2s-S3s, C100s-D101s, and D101s-R102s
      were cleaved to form non-covalently bound subunits (29 kDa and 9 kDa) by
      eliminating the disulfide bonds in the plant-specific region of the protein.

PMID- 11330697
TI  - New quinoline alkaloids from the leaves and stems of Orixa japonica, orijanone,
      isopteleflorine and 3'-O-methylorixine.
AB  - Orixajaponica (Rutaceae) is a shrub widely distributed in Japan, and has been
      found to contain various quinoline alkaloids. We investigated the alkaloidal
      constituents of O. japonica, and four quinoline alkaloids were isolated and
      characterized. Three of these alkaloids are new natural products.

PMID- 11330698
TI  - Unique occurrence of the 1CF11 carbohydrate epitope in primate saliva.
AB  - We examined a large number of individual human and animal saliva samples for the
      reactivity with ICF11, a mouse monoclonal antibody previously produced for the
      characterization of human milk mucin and apparently recognizing a certain
      carbohydrate antigenic structure shared by various human glycoproteins in
      secretions. The results obtained here confirm the unique occurrence of ICF11
      epitope in each and every saliva sample from humans and Old world monkeys as
      well, though a vast variety was observed among individual saliva samples in the
      immunological reactivity with ICF11.

PMID- 11330699
TI  - Primary structure and phylogenetic analysis of the coat protein of a Toyama
      isolate of tobacco necrosis virus.
AB  - The amino acid sequence of the coat protein (CP) of a tobacco necrosis virus
      (TNV) strain, Toyama isolate, was determined by a combination of peptide and cDNA
      sequencing. The deduced sequence of 276 residues was compared with CPs of other
      TNV isolates and other plant virus isolates of Tombusviridae. It showed the
      highest similarity to the TNV Nebraska isolate with 92% identity and moderate
      similarity to the TNV strain A with 51% identity, confirming the previous
      serological analysis. It also showed overall similarity with CPs of mostly genera
      Necrovirus and Sobemovirus, and partial similarity with CPs of genera Tombusvirus
      and Carmovirus. Among 13 CPs that showed overall similarity, there were 10
      completely conserved residues. These included three residues that participate in
      Ca2+ ligation at the interfaces of virion subunits in TNV crystal structure,
      suggesting that similar metal binding occur in the viruses of genera Necrovirus
      and Sobemovirus.

PMID- 11330700
TI  - The est1 regulation depends on the oxygen concentration in Acetobacter
      pasteurianus.
AB  - The regulation mechanism for expression of the ethanol inducible esterase gene,
      est1, was investigated in A. pasteurianus. Deletion analysis of the 5' non coding
      region of est1 showed that the FNR-binding consensus sequence is important in the
      induction of est1 by ethanol. Cells grown under oxygen starvation produced
      esterase-1 in not only the presence but also the absence of ethanol. These
      results suggest that the induction of est1-expression depends on the oxygen
      concentration, and the gene may be induced by a FNR-like factor activated by a
      decrease in the intracellular oxygen concentration.

PMID- 11330701
TI  - MUP1, high affinity methionine permease, is involved in cysteine uptake by
      Saccharomyces cerevisiae.
AB  - Using a mutant defective in cysteine uptake, which is resistant to a toxic analog
      of cysteine, allylglycine, we searched for a gene that complements the defect in
      cysteine uptake in a yeast genomic library and found a DNA fragment causing the
      recovery of cysteine uptake and sensitivity to allylglycine. The gene in the
      fragment was identical to MUP1, the high affinity methionine permease gene. We
      conclude that Mup1 is a major permease in cysteine uptake.

PMID- 11330702
TI  - Synthesis of gibbilimbols A-D, cytotoxic and antibacterial alkenylphenols
      isolated from Piper gibbilimbum.
AB  - Gibbilimbols A [(E)-4-(4-decenyl)phenol, 1], B [(E)-4-(3-decenyl)phenol, 2], C
      [(E)-4-(4-octenyl)phenol, 3] and D [(E)-4-(3-octenyl)phenol, 4] were synthesized
      by coupling the phenolic parts with the alkyne parts and then reducing the triple
      bond of the resulting alkynylphenols. These alkenylphenols (1-4) are the
      cytotoxic and antibacterial constituents of the leaves of a medicinal plant
      (Piper gibbilimbum) that is used as a traditional medicine in Papua New Guinea.

PMID- 11330703
TI  - Designing potent derivatives of ovokinin(2-7), an anti-hypertensive peptide
      derived from ovalbumin.
AB  - We obtained a potent anti-hypertensive peptide, RPFHPF, by replacing the amino
      acid residues of ovokinin(2-7) (RADHPF), an orally active anti-hypertensive
      peptide derived from ovalbumin. After intravenous administration in anesthetized
      Wistar rats, the designed peptide [Pro2, Phe3]-ovokinin(2-7) had a long-lasting
      hypotensive activity at a dose of 10 mg/kg, while that of ovokinin(2-7) was only
      transient even at a dose of 100 mg/kg. After oral administration in conscious
      spontaneously hypertensive rats (SHRs), [Pro2, Phe3]-ovokinin(2-7) significantly
      lowered the systolic blood pressure in a dose-dependent manner. It is noteworthy
      that the minimum effective dose of [Pro2, Phe3]-ovokinin(2-7) was 0.3 mg/kg,
      about one-thirtieth of that of ovokinin(2-7). On the other hand, orally
      administered [Pro2, Phe3]-ovokinin(2-7) did not show any significant hypotensive
      effect in normotensive Wistar-Kyoto rats (WKYs) even at a dose of 3 mg/kg. Taken
      together, [Pro2, Phe3]-ovokinin(2-7) proved to be an ideal, potent anti
      hypertensive peptide with little effect on normal blood pressure when given
      orally.

PMID- 11330704
TI  - Structures of azaspiracid analogs, azaspiracid-4 and azaspiracid-5, causative
      toxins of azaspiracid poisoning in Europe.
AB  - Two new analogs of azaspiracid, azaspiracid-4 and azaspiracid-5, isolated from
      the mussel Mytilus edulis, involved in a newly emerged shellfish poisoning in
      Europe were determined to be 3-hydroxy-22-demethylazaspiracid and 23-hydroxy-22
      demethylazaspiracid, respectively.

PMID- 11330705
TI  - The production of cytotoxic lignans by plant cell cultures.
AB  - Cytotoxic lignans derived from podophyllotoxin are currently used in cancer
      chemotherapy. Podophyllotoxin for semi-synthetic derivatization is isolated from
      the rhizomes of Podophyllum plants growing wild, some of which are counted as
      endangered species. An alternative source for podophyllotoxin or related lignans
      may in future be cell cultures derived from different plant species, such as
      Podophyllum spp or Linum spp. These cell cultures were shown to accumulate
      considerable amounts of podophyllotoxin or 5-methoxypodophyllotoxin. Optimization
      of the cell cultivation regime might lead to a renewable source of cytotoxic
      lignans for medicinal uses. This Mini-Review summarizes the attempts to establish
      plant cell cultures for the production of podophyllotoxin and related lignans and
      their optimization towards high levels of these target compounds. It also
      summarizes the results of studies on the biosynthesis of podophyllotoxin and 5
      methoxypodophyllotoxin.

PMID- 11330706
TI  - Plate screening methods for the detection of polysaccharase-producing
      microorganisms.
AB  - Polysaccharide-degrading enzymes (polysaccharases) are widely applied in
      industry. One of the sources of these enzymes are polysaccharide-degrading
      microorganisms. To obtain such microorganisms from enrichment cultures, strain
      collections or gene libraries, efficient plate screening methods are required
      that discriminate between intact and degraded polysaccharide. This can be
      achieved by making use of specific physicochemical properties of the
      polysaccharide, such as complex formation with dyes and gelling capacity, or by
      the application of dye-labelled polysaccharides. This review presents a survey of
      plate methods based on these principles. Both theoretical and practical aspects
      of the methods are discussed.

PMID- 11330707
TI  - Purification and characterization of the enantioselective nitrile hydratase from
      Rhodococcus equi A4.
AB  - The nitrile hydratase from Rhodococcus equi A4 consisted of two kinds of subunits
      which slightly differed in molecular weight (both approximately 25 kDa) and
      showed a significant similarity in the N-terminal amino acid sequences to those
      of the nitrile hydratase from Rhodococcus sp. N-774. The enzyme preferentially
      hydrated the S-isomers of racemic 2-(2-, 4-methoxyphenyl)propionitrile, 2-(4
      chlorophenyl)propionitrile and 2-(6-methoxynaphthyl)propionitrile
      (naproxennitrile) with E-values of 5-15. The enzyme functioned in the presence of
      5-98% (v/v) of different hydrocarbons, alcohols or diisopropyl ether. The
      addition of 5% (v/v) of n-hexane, n-heptane, isooctane, n-hexadecane, pristane
      and methanol increased the E-value for the enzymatic hydration of 2-(6
      methoxynaphthyl)propionitrile.

PMID- 11330708
TI  - Beta-glucosidase multiplicity from Aspergillus tubingensis CBS 643.92:
      purification and characterization of four beta-glucosidases and their
      differentiation with respect to substrate specificity, glucose inhibition and
      acid tolerance.
AB  - From Aspergillus tubingensis CBS 643.92 four distinct beta-glucosidases (I-IV)
      were purified by a four-step purification procedure. SDS-PAGE revealed molecular
      masses of 131, 126, 54 and 54 kDa, respectively, and their isoelectric points
      were determined to be 4.2, 3.9, 3.7 and 3.6, respectively. The beta-glucosidases
      exhibited high diversity with respect to pH and temperature optima and stability,
      as well as to substrate specificity and glucose tolerance. The major beta
      glucosidase (I) preferentially hydrolysed oligosaccharides. The acid-stable and
      heat-tolerant beta-glucosidase II hydrolysed aryl and terpenyl beta-D-glucosides
      as well as 1-O-trans-cinnamoyl beta-D-glucoside. In contrast to beta-glucosidases
      I and II, the minor beta-glucosidases III and IV were found to be glucose
      tolerant; inhibition constants of 470 and 600 mM, respectively, were determined.

PMID- 11330709
TI  - Enhanced anthocyanin production by repeated-batch culture of strawberry cells
      with medium shift.
AB  - Repeated-batch cultures of strawberry cells (Fragaria ananassa cv. Shikinari)
      subjected to four medium-shift procedures (constant LS medium, constant B5
      medium, alternation between LS and B5 starting from LS and alternation between LS
      and B5 starting from B5) were investigated for the enhanced anthocyanin
      productivity. To determine the optimum period for repeated batch cultures, two
      medium-shift periods of 9 and 14 days were studied, which represent the end of
      the exponential growth phase and the stationary phase. By comparison with the
      corresponding batch cultures, higher anthocyanin productivity was achieved for
      all the repeated-batch cultures at a 9-day medium-shift period. The average
      anthocyanin productivity was enhanced 1.7- and 1.76-fold by repeated-batch
      cultures in constant LS and constant B5 medium at a 9-day shift period for 45
      days, respectively. No further improvement was observed when the medium was
      alternated between LS (the growth medium) and B5 (the production medium).
      Anthocyanin production was unstable at a 14-day shift period regardless of the
      medium-shift procedures. The results show that it is feasible to improve
      anthocyanin production by a repeated-batch culture of strawberry cells.

PMID- 11330710
TI  - Characteristics and N-terminal amino acid sequence of manganese peroxidase from
      solid substrate cultures of Agaricus bisporus.
AB  - Extracellular manganese peroxidase (MnP) was purified from the compost extract of
      Agaricus bisporus using anion exchange chromatography, gel filtration and sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Two forms (MnP1
      and MnP2) were separated by isoelectric focusing and their isoelectric points
      were determined to be 3.25 (MnP1) and 3.3 (MnP2). Both forms had a molecular mass
      of 40 kDa. The first 25 amino acids of the N-terminal end of MnP1 sequence was
      found to share 68% identity with a Pleurotus ostreatus and a P. eryngii MnP.
      Lignin peroxidase was not detected during any of the steps in the purification
      process. In liquid cultures with both soluble and insoluble carbon sources in
      defined medium (D-glucose, glycerol, Whatman CC-41 microcrystalline cellulose or
      Solka-floc cellulose) MnP protein was detected in culture fluid by Western blot,
      but no MnP activity could be detected. A. bisporus appears to be in the group of
      ligninolytic fungi which do not produce lignin peroxidase.

PMID- 11330711
TI  - Chemo-enzymatically induced copolymerization of phenolics with acrylate
      compounds.
AB  - Initiation of copolymerization of lignin-like phenolic and acrylic compounds by
      the phenoloxidase laccase (EC 1.10.3.2) and a peroxide species (t
      butylhydroperoxide, t-BHP) was compared to a Fenton-like system (ferrous ion, t
      BHP). Initially, the relative activity of laccase towards different phenolic
      compounds and the optimum pH of some characteristic phenolics were determined.
      The polymer yield and the average molecular weight (Mw) of chemo-enzymatically
      produced polymers were dependent both on the type of each phenolic tested and on
      the phenol/monomer ratio. Furthermore, the success of copolymerization of the
      phenolics was dependent both on their redox potential and on the type of acrylic
      monomer applied. The extent of phenol incorporation into the polymer chain was
      enhanced by the presence of laccase in the reaction mixture and was significantly
      higher than in polymerization initiated by a Fenton-like reaction.

PMID- 11330712
TI  - High-level production of heme-containing holoproteins in Escherichia coli.
AB  - The expression of recombinant protein is essential for the investigation of the
      functions and properties of heme-containing protein as an electron carrier. For
      the expression of fully active recombinant protein, conversion of the expressed
      apoprotein into holoprotein is the most important and difficult problem. In this
      study, a system was developed for the production of heme-containing protein in a
      pure, recombinant holoprotein form, using the bovine cytochrome b5 tryptic
      fragment and Escherichia coli bacterioferritin as heterologous and homologous
      heme-containing model proteins, respectively. This system is based on the slow
      synthesis of recombinant apoprotein, which can maintain the balanced consumption
      of amino acids between protein synthesis and heme synthesis, so that the
      synthesized apoprotein continues to act as a heme sink. From a 1-1 culture, 15 mg
      of cytochrome b5 and 40 mg of bacterioferritin were purified as pure holoprotein
      forms. Our expression system provides a rapid and simple method for obtaining
      large quantities of the active holo-form of heme-containing proteins.

PMID- 11330713
TI  - Identification of an intragenic integration site for foreign gene expression in
      recombinant Streptococcus gordonii strains.
AB  - A new intragenic chromosomal integration site within the lacG gene of the lac
      operon has been identified in Streptococcus gordonii for use in the expression of
      foreign genes. Introduction of a portion of the Streptococcus pyogenes emm6 gene
      into the lacG locus resulted in the lactose-inducible surface expression of the
      S. pyogenes M6 protein. This result demonstrates the ability to modulate the in
      vitro or in vivo expression of a foreign gene in a S. gordonii recombinant using
      a biosynthetic metabolite.

PMID- 11330714
TI  - Gene synthesis, expression in E. coli, and in vitro refolding of Pseudomonas sp.
      KWI 56 and Chromobacterium viscosum lipases and their chaperones.
AB  - Pseudomonas lipases are industrially used as detergent additives, in the food
      industry, and in organic synthesis. Currently, these lipases are either isolated
      from wild-type strains or overexpressed in recombinant Pseudomonas host strains
      which may be subject to special safety regulations and thus be unsuitable for
      enzyme engineering via directed evolution. Here we describe the heterologous
      expression of two Pseudomonas lipases in Escherichia coli. The lipase genes of
      Pseudomonas sp. KWI 56 (recently reclassified as Burkholderia cepacia) and
      Chromobacterium viscosum and the genes of their specific chaperones, which are
      required for correct folding, were synthesized with an optimized nucleotide
      sequence and overexpressed (up to 50%) in E. coli. However, both lipases were
      inactively expressed inside inclusion bodies. Quantitative in vitro refolding of
      the lipases in the presence of their specific chaperones yielded 310,000 U/g
      (Pseudomonas sp. KWI 56) and 190,000 U/g (C. viscosum) wet cells. In addition,
      these lipases could be demonstrated to refold efficiently in the presence of
      chaperones of related lipases.

PMID- 11330715
TI  - Heterologous expression of the acyl-acyl carrier protein thioesterase gene from
      the plant Umbellularia californica mediates polyhydroxyalkanoate biosynthesis in
      recombinant Escherichia coli.
AB  - The acyl-acyl carrier protein (ACP) thioesterase cDNA from the plant Umbellularia
      californica was functionally expressed in various recombinant Escherichia coli
      strains in order to establish a new metabolic route toward medium-chain-length
      polyhydroxyalkanoate (PHA(MCL)) biosynthesis from non-related carbon sources.
      Coexpression of the PHA synthase genes from Ralstonia eutropha and Pseudomonas
      aeruginosa, or only the PHA synthase gene from P. aeruginosa, respectively,
      showed PHA(MCL) accumulation when the type II PHA synthase from P. aeruginosa was
      produced. Both wild-type E. coli and various fad mutants were investigated; and
      only when the beta-oxidation pathway was impaired PHA(MCL) accumulation from
      gluconate was observed, contributing to about 6% of cellular dry weight. Thus
      coexpression of type II PHA synthase gene with cDNA encoding the medium-chain
      acyl-ACP thioesterase from U. californica established a new PHA(MCL) biosynthesis
      pathway, connecting fatty acid de novo biosynthesis with fatty acid beta
      oxidation, using a non-related carbon source.

PMID- 11330716
TI  - Screening of micro-organisms for decolorization of melanins produced by bluestain
      fungi.
AB  - A total of 17 fungi and four bacteria were screened for their ability to
      decolorize melanin, using isolated extracellular melanin of the bluestain fungus
      Aureobasidium pullulans as substrate. On agar media, decolorization was observed
      by four fungal strains: Bjerkandera adusta VTT-D-99746, Galactomyces geotrichum
      VTT-D-84228, Trametes hirsuta VTT-D-95443 and Trametes versicolor VTT-D-99747.
      The four fungi were more efficient on nitrogen-limited medium than on complete
      medium. The melanin-decolorizing activity of G. geotrichum appeared to be located
      on the mycelium and could be liberated into the medium enzymatically.

PMID- 11330717
TI  - Improved osmotolerance of recombinant Escherichia coli by de novo glycine betaine
      biosynthesis.
AB  - The genes from the extreme halophile Ecto-thiorhodospira halochloris encoding the
      biosynthesis of glycine betaine from glycine were cloned into Escherichia coli.
      The accumulation of glycine betaine and its effect on osmotolerance of the cells
      were studied. In mineral medium with NaCl concentrations from 0.15 to 0.5 M, the
      accumulation of both endogenously synthesized and exogenously provided glycine
      betaine stimulated the growth of E. coli. The intracellular levels of glycine
      betaine and the cellular yields were clearly higher for cells receiving glycine
      betaine exogenously than for cells synthesizing it. The lower level of glycine
      betaine accumulation in cells synthesizing it is most likely a consequence of the
      limited availability of precursors (e.g. S-adenosylmethionine) rather than the
      result of a low expression level of the genes. Glycine betaine also stimulated
      the growth of E. coli and decreased acetate formation in mineral medium with high
      sucrose concentrations (up to 200 g.l(-1)).

PMID- 11330718
TI  - Studies on the possibility of histidine biosynthesis from histodinol,
      imidazolepyruvic acid, imidazoleacetica acid, and imidazolelactic acid by mixed
      ruminal bacteria, protozoa, and their mixture in vitro.
AB  - The possibility of histidine (His) synthesis using a main biosynthetic pathway
      involving histidinol (HDL) and also the recycling capability of imidazolic
      compounds such as imidazolepyruvic acid (ImPA), imidazoleacetic acid (ImAA), and
      imidazolelactic acid (ImLA) to produce His were investigated using mixed ruminal
      bacteria (B), protozoa (P), and a mixture of both (BP) in an in vitro system.
      Rumen microorganisms were anaerobically incubated at 39 degrees C for 18 h with
      or without each substrate (2 mM) mentioned. His and other related compounds
      produced in both the supernatants and hydrolyzates of the incubation were
      analyzed by high-performance liquid chromatography. B, P, and BP suspensions
      failed to show His synthesizing ability when incubated with HDL. His was
      synthesized from ImPA by B, P, and BP. Expressed in units "per gram of microbial
      nitrogen (MN)", ImPA disappearance was greatest in B (72.7 micromol/g MN per
      hour), followed by BP (33.13 micromol/g MN per hour) and then P (18.6 micromol/g
      MN per hour) for the 18-h incubation period. The production of His from ImPA in B
      (240.0, 275.9, and 261.2 micromol/g MN in 6, 12, and 18 h incubation,
      respectively) was about 3.5 times higher than that in P (67.3, 83.8, and 72.7
      micromol/g MN in 6, 12, and 18 h incubation, respectively). Other metabolites
      produced from ImPA were ImLA, ImAA, histamine (HTM), and urocanic acid (URA),
      found in all microbial suspensions. ImLA as a substrate remained without
      diminution in all microbial suspensions. Although ImAA was found to be degraded
      to a small extent (3.4-6.3%) only after 18 h incubation, neither His nor other
      metabolites were detected on the chromatograms. These results have been
      demonstrated for the first time in rumen microorganisms and suggest that His may
      be an essential amino acid for rumen microorganisms.

PMID- 11330719
TI  - Influence of glucose on glycerol metabolism by wild-type and mutant strains of
      Clostridium butyricum E5 grown in chemostat culture.
AB  - In order to improve the yield of 1,3-propanediol (1,3-PPD) in Clostridium
      butyricum E5, we carried out cofermentation experiments on glucose/glycerol
      mixtures in chemostat culture. The results showed the influence of the ratio of
      the two carbon substrates on the production of the required diol. The progressive
      increase of glucose in culture medium containing a given concentration of
      glycerol made it possible to highlight the deviation of carbon flow from the
      oxidative towards the reducing pathway, in order to maintain the
      oxidation/reduction balance in the cell. The conversion of glycerol into 1,3-PPD
      thus increased from 0.63 mol mol(-1), without the addition of glucose, to a
      maximum of 0.89 mol mol(-1) for a molar glucose/glycerol ratio of 0.2 for the
      wild-type strain. The same experiments carried out with the mutant MD strain,
      which is resistant to allyl alcohol, led to similar results but with a maximum of
      0.84 mol mol(-1) for a glucose/glycerol molar ratio of 0.1. Beyond a molar ratio
      of 0.2, the biosynthesis of enzymes for the glycerol metabolism was less subject
      to catabolic repression by glucose in the mutant MD strain than in the wild-type
      strain.

PMID- 11330720
TI  - A calorimetrically based method to convert toxic compounds into poly-3
      hydroxybutyrate and to determine the efficiency and velocity of conversion.
AB  - A fed-batch method for converting toxic substrates into poly-3-hydroxybutyrate is
      presented. The method involves a series of batch-growth processes, regulated by
      adding small amounts of carbon substrate, during the course of which the
      concentration of the nitrogen source decreases and controls the distribution of
      the substrate-carbon assimilated. The addition of carbon substrate is controlled,
      and the small changes that occur in the growth pattern are interpreted using high
      resolution reaction calorimetry. The method was tested with Ralstonia eutropha
      DSM 4058 growing on phenol, and Variovorax paradoxus DSM 4065 growing on sodium
      benzoate. The maximum carbon conversion efficiencies (CCEs) obtained, 23% and 27%
      respectively, were compared with the theoretically possible values.

PMID- 11330721
TI  - Dehalogenation of dichloroethene in a contaminated soil: fatty acids and alcohols
      as electron donors and an apparent requirement for tetrachloroethene.
AB  - Environmental soil contamination at an industrial site in Marion, Ohio (USA) with
      tetrachloroethene (perchloroethene, PCE) resulted in residual cis-1, 2
      dichloroethene (DCE) contamination that had not declined after more than 15
      years. Microcosm slurries containing 2.6% soil from this site were supplemented
      with different electron donors, i.e., individual fatty acids or alcohols. None of
      the microcosms supported complete DCE dechlorination, unless PCE was added to the
      microcosm at initiation. The addition of fresh PCE resulted in the dehalogenation
      of PCE to DCE in the microcosms supplemented with fatty acids having an even
      number of carbon atoms (acetate, butyrate, and caproate), but not in those with
      an odd number of carbon atoms (formate, propionate, and valerate), where
      negligible or no activity was detected. No significant further DCE degradation
      was observed in any of the microcosms supplied with fatty acids as electron
      donors. Microcosms supplemented with freshly added PCE bioconverted PCE to DCE
      and completely dehalogenated both the ex-novo and soil-supplied DCE within 60
      days, but only if alcohols having an even number of carbon atoms (ethanol or
      butanol) were also added as electron donors. Odd-numbered alcohols either did not
      produce dehalogenation (as with methanol) or only dehalogenated PCE to DCE (as
      with propanol).

PMID- 11330722
TI  - Diversity in kinetics of trichloroethylene-degrading activities exhibited by
      phenol-degrading bacteria.
AB  - Whole-cell kinetics of phenol- and trichloroethylene (TCE)-degrading activities
      expressed by 13 phenol-degrading bacteria were analyzed. The Ks (apparent
      affinity constant in Haldane's equation) values for TCE were unexpectedly
      diverse, ranging from 11 microM to over 800 microM. The Vmax/Ks values for phenol
      were three orders of magnitude higher than the values for TCE in all bacteria
      analyzed, suggesting that these bacteria preferentially degrade phenol rather
      than TCE. A positive correlation between Ks for phenol and Ks for TCE was found,
      i.e., bacteria exhibiting high Ks values for phenol showed high Ks values for
      TCE, and vice versa. A comparison of the Ks values allowed grouping of these
      bacteria into three types, i.e., low-, moderate- and high-Ks types. Pseudo-first
      order degradation-rate constants for TCE at 3.8 microM were found to be adequate
      to rapidly discriminate among the three types of bacteria. When bacteria were
      grown on phenol at the initial concentration of 2 mM, Comamonas testosteroni
      strain R5, a representative of low-Ks bacteria, completely degraded TCE at 3.8
      microM, while strain P-8, a representative of high-Ks bacteria, did not. A mixed
      culture of these two bacteria poorly degraded TCE under the same conditions,
      where P-8 outgrew R5. These results suggest that low-Ks bacteria should be
      selectively grown for effective bioremediation of TCE-contaminated groundwater.

PMID- 11330723
TI  - Parameters affecting performance and modeling of biofilters treating alkylbenzene
      polluted air.
AB  - Both short-term and long-term biofiltration experiments were undertaken with a
      biofilter inoculated with a defined microbial consortium and treating an
      alkylbenzene mixture. The results obtained with such a biofilter in short-term
      experiments were very similar to those obtained with a biofilter inoculated with
      a non-defined mixed culture, in terms of maximum elimination capacities (70-72 g
      m(-3) h(-1)) and the corresponding removal efficiencies (>95%). However, in long
      term experiments, a better performance was reached, with a maximum elimination
      capacity of 120 g m(-3) h(-1), corresponding to a removal efficiency >99% after 2
      years of operation. Inoculation proved to be useful for shortening the start-up
      period. In the long term, it appeared that biomass distribution was not
      homogenous along the biofilter, which in some cases resulted in a bad fit between
      simple model equations and experimental data.

PMID- 11330724
TI  - Chien-Tien Hsu Memorial Lecture. Fertility and gynaecologic malignancies.
AB  - Fertility and gynaecological malignancies have an important relationship. A clear
      inverse relationship exists between family size and the incidence of ovarian and
      endometrial cancer. Current methods of fertility control have an influence on
      subsequent development of various gynaecological malignancies. A slightly
      increased risk of breast cancer has been reported in current users and those who
      had used hormonal contraceptives (OCs) within 10 years; this risk declined with
      time and disappeared after 10 years. Women who started OC before age 20 had a
      higher relative risk; the disease did not spread beyond the breast in the
      majority. Most studies found OC to reduce the risk of ovarian and endometrial
      cancer. The relative risks of squamous cell carcinoma and adenomatous carcinoma
      of the cervix have been reported to be 1.3 and 1.5, respectively in ever-users of
      OCs; however, the aetiology of cervical cancer is multifactoral. Several reports
      suggest the beneficial effect of tubal ligation and breast feeding in reducing
      the risk of ovarian cancer. Therapy of gynaecological malignancies may have an
      influence on subsequent fertility. Amenorrhoea developing after treatment of
      hydatidiform mole may be due to choriocarcinoma, recurrent mole or a normal
      pregnancy. Choriocarcinoma can also develop after a partial mole. The risk of
      fetal teratogenicity from chemotherapy is present only if conception occurs
      during or immediately following the treatment cycles. Fertility is not impaired
      following chemotherapy. Successful pregnancies have occurred in women who have
      had widespread GTD including cerebral metastases. In the young patient with
      gynaecological malignancy preservation of fertility is possible. Fertility
      sparing surgery may be safe in early ovarian epithelial cancers and even in
      advanced germ cell tumours. Recently, the fertility-sparing surgery of radical
      trachelectomy and pelvic lymphadenectomy has been carried out for early invasive
      cervical cancer in young women. Gynaecological cancer occurring in pregnancy is
      uncommon; it presents the clinician with a difficult situation to manage. In most
      instances the cancer is treated as though the patient is not pregnant; the timing
      and mode of delivery needs individualization. The overall prognosis for breast
      cancer complicating pregnancy is poor. Survival in cervical cancers diagnosed
      antepartum is similar to the non-pregnant patient. Ovarian cancer in pregnancy
      has a good prognosis because of the early stage at diagnosis.

PMID- 11330725
TI  - Misoprostol in labor induction.
AB  - The efficacy of a new dosing regimen of misoprostol, a recently introduced labor
      inducing agent, was studied. Fifty-eight patients received 50 microg of
      misoprostol intravaginally and the dose was repeated every 3 hours until uterine
      contractions begin. Those who had an adequate contraction pattern, defined as
      three contractions in 10 minutes, were not given the repeat dose. Oxytocin
      augmentation, but not further misoprostol doses, was used in patients with an
      inadequate contraction pattern. The maximum total daily dose was 200 microg. The
      patients had the mean age of 28.9 +/- 5.4, the mean gestational age of 211.8 +/-
      46.6 days, the mean gravidity of 2.5 +/- 1.2, the mean parity of 0.9 +/- 0.9 and
      the mean initial Bishop score of 1.6 +/- 1.8. The mean required dose of
      misoprostol was 120.5 +/- 54.7 microg and 10 of 58 patients required oxytocin
      augmentation. The mean induction of labor to delivery time was 701.5 +/- 404.0
      minutes. When 3 cases who gave birth with caesarean section were excluded, the
      interval was 708.4 +/- 407.2 minutes. The mean 5th minute Apgar score of the
      newborns was 8.2 +/- 2.5. Two patients developed tachysystole after the second
      dose of misoprostol and were managed with vaginal irrigation and O2
      supplementation successfully. Slight nausea and vomiting in 2 patients were the
      other adverse reactions. Our findings revealed that, 50 microg intravaginal
      misoprostol, combined with oxytocin augmentation when necessary, appears to be an
      effective and safe method of labor induction.

PMID- 11330726
TI  - Neurogenic cyst of ovary: an unusual massive monodermal teratoma.
AB  - An unusual massive benign cystic monodermal teratoma of the ovary in a 14-year
      old girl is reported. The multilocular cyst measured 80 x 70 x 80 cm and
      contained 23 l of fluid. The cyst wall composed of purely mature central nervous
      system tissue with a prominent microvasculature resting on a thin rim of ovarian
      cortical tissue. Immunohistochemical stains supported the diagnosis. To the best
      of our knowledge only one such case has been described in the literature.

PMID- 11330727
TI  - Waist to hip circumference ratio as a significant predictor of preeclampsia,
      irrespective of overall adiposity.
AB  - OBJECTIVE: To investigate whether abnormal body fat distribution is a significant
      predictor of the development of preeclampsia, irrespective of overall adiposity.
      METHODS: Twenty-six women with preeclampsia and 198 control women were enrolled.
      Waist to hip circumference ratio (WHR), body weight (BW), and body mass index
      (BMI, wt/ht2) were measured early in pregnancy (< 9 weeks of gestational age).
      Age, height, parity, tobacco usage, education period, gestational duration, and
      weight gain during pregnancy were also recorded for each subject. RESULTS: WHR,
      BMI, and BW early in pregnancy were significantly higher in the preeclampsia
      group (p < 0.0001). WHR, BMI, and BW positively correlated with the development
      of preeclampsia on univariate regression analysis (Standardized regression
      coefficient = 0.410, 0.387, and 0.363, respectively, p < 0.0001). On stepwise
      multiple regression analysis, WHR still correlated with the development of
      preeclampsia irrespective of BMI and BW. When the WHR predictive of the
      development of preeclampsia was set at 0.9, the sensitivity was 46.2% (12/26),
      which was significantly better than that of 25 of BMI (19.2%, 5/26; p < 0.05).
      CONCLUSION: Higher WHR is a significant predictor of the development of
      preeclampsia. This relation is irrespective of overall adiposity.

PMID- 11330728
TI  - Phenobarbital following phototherapy for Crigler-Najjar syndrome type II with
      good fetal outcome: a case report.
AB  - In the presence of severe hyperbilirubinemia in Crigler-Najjar syndrome Type II,
      a fetus is at risk for kernicterus. A 34-year-old woman, gravida 4, para 1, with
      Crigler-Najjar syndrome Type II was treated with phenobarbital administration
      following phototherapy during each of 2 pregnancies. Both infants were healthy
      and developed normally.

PMID- 11330729
TI  - Antenatal diagnosis of prune belly syndrome at 11 weeks of gestation.
AB  - We present a case of prune belly syndrome diagnosed by ultrasonography at 11
      weeks of gestation. We believe this case to be the earliest detection of this
      syndrome.

PMID- 11330730
TI  - Rapid detection of chromosome aneuploidies by prenatal interphase FISH
      (fluorescence in situ hybridization) and its clinical utility in Japan.
AB  - OBJECTIVE: The purpose of this study was to assess the accuracy, informative
      rate, detection rate, and clinical utility of prenatal interphase fluorescence in
      situ hybridization (FISH) analysis of amniotic fluid samples from Japanese women.
      METHODS: Amniotic fluid specimens from 2,639 Japanese women were received for
      prenatal interphase FISH and chromosome analysis. A questionnaire was designed to
      evaluate FISH clinical utility by collaboration sites. RESULTS: Based on 2,319
      tested samples, the accuracy (100%), informative (94%), and detection (87.6%)
      rates were all high. The accuracy (100%), informative (90.2%), and detection
      (90.0%) rates were also remarkable in third-trimester pregnancies. We perceive
      significant advantages from this test regarding medical management and patient
      satisfaction. CONCLUSIONS: This novel report shows that in Japan prenatal
      interphase FISH testing is highly informative and accurate, not only in second
      trimester pregnancies but also in third-trimester pregnancies. This test provides
      advantages to both physicians and patients, provided that its capabilities and
      limitations are understood.

PMID- 11330731
TI  - Metastatic placental site trophoblastic tumor: a case report.
AB  - Placental site trophoblastic tumor (PSTT) is very rare. It is an unusual variant
      of gestational trophoblastic neoplasia usually confined to the uterus, although
      10% of patients have metastases. The clinical behaviour of PSTT varies and
      despite knowledge of its histology, diagnosis of this rare form of trophoblastic
      disease and prediction of its biological behaviour remains difficult due to only
      a few cases reported in literature.

PMID- 11330732
TI  - Nitric oxide mediates inhibitory effect of interleukin-1beta on estrogen
      production in human granulosa-luteal cells.
AB  - OBJECTIVE: To investigate the effect of IL-1beta on NO production and
      steroidogenesis in human granulosa-luteal cells obtained from women undergoing in
      vitro fertilization procedures. SUBJECTS AND METHODS: To investigate the effect
      of IL-1beta, granulosa-luteal cells were cultured with various doses of IL-1beta
      (0, 0.05, 0.5, 5, 50, 100 ng/ml), IL-1beta (5 ng/ml) with NG-nitro-L-arginine
      methyl ester (L-NAME), selective inhibitors of NOS, sodium nitroprusside (SNP),
      NO donors and Genistain, a tyrosine kinase inhibitor. RESULTS: IL-1beta induced a
      dose-dependent stimulation of NO production and inhibited the production of
      estradiol in a significant way in a dose-dependent manner. L-NAME significantly
      decreased NO production and increased the production of estradiol and
      progesterone. SNP significantly increased NO production and caused decreases in
      the production of both estradiol and progesterone. Genistain decreased NO
      production and significantly increased the production of estradiol and
      progesterone. Inducible NOS (iNOS) messenger RNA was present in granulosa-luteal
      cells before treatment with IL-1beta. CONCLUSIONS: IL-1beta stimulated NO
      production, and NO inhibited the production of estradiol.

PMID- 11330733
TI  - Grand Hamdan International Award.

PMID- 11330734
TI  - Microembolic signals in patients undergoing coronary artery bypass grafting.
      Effect of aortic atherosclerosis.
AB  - The aim of this prospective study was to determine whether aortic atherosclerotic
      plaques are associated with increased frequency of microembolic signals and
      stroke in patients who undergo coronary artery bypass grafting. A total of 69
      such patients were monitored by transcranial Doppler ultrasonography for 30
      minutes before and after surgery. To our knowledge, this study is the 1st in
      which in vivo pathologic analysis of aortic plaques was systematically performed
      and microembolic signals monitored-before and after open-heart surgery. Plaques
      were assessed by transesophageal echocardiography and by biopsy of materials
      taken during surgery. The frequency of microembolic signals was evaluated with
      regard to the occurrence of postoperative stroke. In the preoperative phase, only
      10 of 48 patients with aortic plaques had microembolic signals, and the mean
      count of microembolic signals was 3.2 +/- 1.2 per hour. At the conclusion of 24
      postoperative hours, 29 patients (42%) displayed such signals (mean count, 9.8 +/
      3.1/h). Seven of the 48 patients (15%) with aortic atherosclerosis had cerebral
      ischemic events, but none of those with normal aorta (21 patients) experienced
      stroke during the postoperative phase. During postoperative monitoring, patients
      with stroke had higher microembolic-signal counts than did those with normal
      aorta (174 +/- 3.3/h vs 5.9 +/- 3.1/h; P <0.05). Our findings suggest that
      microembolic signals can be a marker of severe aortic atherosclerosis and that
      monitoring these signals should enable the application of appropriate surgical
      methods to coronary artery bypass patients who are at higher risk of stroke.

PMID- 11330736
TI  - The Texas Heart Institute Award for Undergraduate Writing in the History of
      Cardiovascular Medicine and Surgery.

PMID- 11330735
TI  - Coronary artery fistula. Management and intermediate-term outcome after
      transcatheter coil occlusion.
AB  - During the last 2 decades, transcatheter occlusion of coronary artery fistulae
      has developed into a safe and effective therapy for children. This procedure
      avoids the need for open surgical repair and the attendant complications of
      cardiopulmonary bypass and median sternotomy. The long-term outcome in patients
      after transcatheter occlusion remains unknown. We describe the intermediate-term
      progress of 4 such patients after coil occlusion of coronary artery fistulae.
      Persistent coronary artery dilatation was present in all patients reviewed, as
      late as 4 years after occlusion.

PMID- 11330737
TI  - Charles Theodore Dotter. The father of intervention.
AB  - The 1st percutaneous transluminal angioplasty marked a new era in the treatment
      of peripheral atherosclerotic lesions. The early techniques used in peripheral
      percutaneous transluminal angioplasty form the basis for subsequent percutaneous
      intervention both in the peripheral and coronary arteries and are largely the
      contribution of Charles Dotter. Dotter was the 1st to describe flow-directed
      balloon catheterization, the double-lumen balloon catheter, the safety guidewire,
      percutaneous arterial stenting, and more. This practical genius dedicated his
      considerable energy to the belief that there is always a better way to treat
      disease. His personal contributions to clinical medicine, research, and teaching
      have saved millions of limbs and lives all over the world.

PMID- 11330738
TI  - The role of interleukin-6 in cases of cardiac myxoma. Clinical features,
      immunologic abnormalities, and a possible role in recurrence.
AB  - We performed this prospective study to evaluate the correlation of interleukin-6
      serum levels with preoperative constitutional symptoms and immunologic
      abnormalities, and the possible role played by this cytokine in tumor recurrence.
      Eight patients with atrial myxoma were evaluated at our institution from July
      1993 to November 1998. We measured their interleukin-6 serum levels by enzyme
      linked immunosorbent assay method preoperatively and 1 and 6 months after
      surgery. Two of the cases involved recurrent tumor, 1 patient had undergone his
      1st surgery at a different institution and died during the 2nd procedure, so his
      data were incomplete. Preoperatively the whole group of patients had elevated
      interleukin-6 serum levels. Although patients with a 1st occurrence of tumor
      demonstrated a positive correlation between interleukin-6 serum level and tumor
      size, the 2 patients with recurrent tumors appeared to have higher interleukin-6
      levels regardless of tumor size. Once the tumor was surgically removed,
      interleukin-6 levels returned to normal values, and this was associated with
      regression of clinical manifestations and immunologic features. According to our
      study, the overproduction of interleukin-6 by cardiac myxomas is responsible for
      the constitutional symptoms and immunologic abnormalities observed in patients
      with such tumors and might also play a role as a marker of recurrence. This study
      also suggests that recurrent cardiac myxomas form a subgroup of cardiac myxomas
      with a highly intrinsic aggressiveness, as implied by their greater interleukin-6
      production despite their smaller size. Further studies are needed to confirm
      these results.

PMID- 11330739
TI  - Replacement of the left common iliac vein with a custom-made bovine pericardium
      tubular graft.
AB  - To date, venous reconstruction has not been as successful as arterial
      reconstruction. Prosthetic materials used as venous substitutes produce much
      lower patency rates with a higher incidence of early thrombosis than those used
      as arterial substitutes. We describe the case of a 38-year-old obese woman in
      whom we encountered an unexpected tear of the common iliac vein intraoperatively,
      during an anterior approach to the lumbar spine. Because of limited options, we
      replaced the vein with an interposition tubulargraft that was custom-made from
      bovine pericardium. Two years later, the patient remained asymptomatic with a
      patent graft. To our knowledge, there has been no other reported case in the
      world medical literature of replacement of medium-sized veins by this technique.

PMID- 11330740
TI  - Transapical aortic cannulation for acute aortic dissection to prevent
      malperfusion and cerebral complications.
AB  - We describe a technique for transapical cannulation in cases of acute aortic
      dissection. This method entails aortic cannulation via the apex of the left
      ventricle and the aortic valve. When this technique is used, retrograde perfusion
      prevents such fatal complications as malperfusion or cerebral embolism that can
      occur with femoral cannulation. Having found no disadvantage in this method, we
      recommend transapical cannulation as the best cannulation technique for acute
      aortic dissection.

PMID- 11330741
TI  - Ever heard of percutaneous transvenous selective coronary angiography? Unusual
      approach in a patient with patent ductus arteriosus.
AB  - Arterial access for coronary angiography is usually achieved by the use of direct
      arterial puncture or, less frequently, by arterial cutdown. We present the case
      of a 39-year-old woman in whom a patent ductus arteriosus was used to enter the
      arterial system for left ventriculography, aortography, and selective coronary
      angiography. To our knowledge, this is the 1st reported case of selective
      coronary angiography with use of a transvenous approach.

PMID- 11330742
TI  - Mitral valve replacement and repair. Report of 5 patients with systemic lupus
      erythematosus.
AB  - Severe mitral valve regurgitation due to systemic lupus erythematosus is a rare
      cause of valvular heart disease, necessitating valve surgery. Currently, there
      are 36 case reports in the world medical literature of mitral valve replacement
      or repair in patients who have lupus. The current trend in mitral valve surgery
      is toward anatomic valve repair. In patients who have systemic lupus
      erythematosus, however, valve repair often leads to repeat surgery and valve
      replacement. We report the cases of 5 patients with lupus and severe mitral valve
      regurgitation who underwent mitral valve surgery. In 3 of these patients,
      replacement with a mechanical prosthetic mitral valve was performed with good
      long-term results. In the other 2 patients, mitral valve repair was performed,
      but only 1 of the repairs was successful. The 2nd patient required subsequent
      replacement with a mechanical valve. To our knowledge, this report of 5 patients
      is the largest series of mitral valve surgery in patients with lupus. These
      results, along with a review of the literature, suggest the superiority of
      mechanical prosthetic valve replacement to repair in patients who have systemic
      lupus erythematosus.

PMID- 11330743
TI  - Mitral valve regurgitation causing right upper lobe pulmonary edema.
AB  - When radiography is performed in patients with mitral regurgitation, cardiogenic
      pulmonary edema is a typical finding; however, asymmetric pulmonary edema has
      also been reported. We describe the case of a patient in whom mitral valve
      regurgitation caused isolated pulmonary edema in the right upper lung. We include
      a discussion of pulmonary edema in conjunction with mitral regurgitation.

PMID- 11330744
TI  - The pitfalls of transthoracic echocardiography. A case of eustachian valve
      endocarditis.
AB  - A case of infective endocarditis involving the vestigial eustachian valve is
      presented and the available English medical literature is reviewed. Only 5 prior
      cases have been reported: 4 of those required transesophageal echocardiography
      for diagnosis, and the other was found at autopsy. This clinical entity is
      routinely missed on transthoracic echocardiography. Injection drug use is a
      common predisposing factor, and Staphylococcus aureus is the most commonly
      identified organism. This report broadens the differential diagnosis of
      endovascular infections in injection drug users and highlights the importance of
      transesophageal echocardiography for diagnosis in selected patients.

PMID- 11330745
TI  - Perfusionist-transmitted bacterial mediastinitis in a heart transplant recipient.
AB  - We report the case of a 56-year-old man who developed bacterial mediastinitis
      with methicillin-resistant Staphylococcus aureus after undergoing heart
      transplantation. He had a history of insulin-dependent diabetes mellitus and
      prior cardiac surgery. To find the source of nosocomial infection, we cultured
      nasal swab specimens from all hospital personnel involved in this operation. We
      used antibiotic sensitivity profiling and pulsed-field gel electrophoresis to
      subtype the involved microorganism. The S. aureus isolates from the patient and
      the perfusionist were identical to each other and were different from the strains
      previously found in our hospital. It is almost certain that the S. aureus
      mediastinitis in this patient was transmitted from the perfusionist. We recommend
      obtaining cultures from hospital staff members when there is an outbreak of
      staphylococcal infection.

PMID- 11330746
TI  - Constrictive pericarditis associated with Marlex mesh. Two case reports.
AB  - Two patients were referred to our hospital with constrictive pericarditis
      approximately 1 year after undergoing mitral valve repair at another institution.
      Both repairs had included the use of a pericardial substitute, Marlex mesh, to
      prevent adhesion and to facilitate possible reoperations. Computed tomography and
      cardiac catheterization were used to establish the diagnosis of constrictive
      pericarditis. During surgery, dense, thickened fibrous tissue, the result of a
      Marlex mesh-related reaction, was found tightly adhered to the epicardium in each
      of the patients. It appeared that the Marlex mesh, which had been inserted to
      facilitate reoperation, had contributed to the development of constrictive
      pericarditis.

PMID- 11330747
TI  - Esophageal perforation in a sword swallower.
AB  - We present the case of a 59-year-old man who sustained an esophageal perforation
      as a result of sword swallowing. An esophagogram established the diagnosis, and
      surgical repair was attempted. However, 19 days later, a persistent leak and
      deterioration of the patient's condition necessitated a transhiatal esophagectomy
      with a left cervical esophagogastrostomy. The patient recovered and has resumed
      his daily activities at the circus, with the exception of sword swallowing. This
      case report presents an unusual mechanism for a potentially lethal injury. Our
      search of the English-language medical literature revealed no other report of
      esophageal perforation resulting from sword swallowing. Management of such an
      injury is often difficult, and a favorable outcome is dependent on prompt
      diagnosis and treatment.

PMID- 11330748
TI  - Twelve-lead electrocardiogram of torsades de pointes.

PMID- 11330749
TI  - Guidewire perforation during PTCA with subsequent off-pump bypass surgery.

PMID- 11330750
TI  - Ebstein's anomaly of the tricuspid valve with associated mitral valve prolapse.

PMID- 11330751
TI  - Cardiac herniation and torsion after partial pericardiectomy during right
      pneumonectomy.

PMID- 11330752
TI  - Curvilinear paramedian sternotomy.

PMID- 11330753
TI  - Femoral hemostasis.

PMID- 11330755
TI  - The 'impact factor'--an explanation and its application to rehabilitation
      journals.
AB  - The impact factor is calculated by dividing the number of times articles from a
      journal are cited in a core of about 5,000 journals by the number of articles
      published by that journal in the same period of two years. It is used as a
      measure of a journal's scientific influence, but the assumptions underlying this
      use are flawed. Although the use of the impact factor is recognized to be
      invalid, nonetheless it continues, in part because no better agreed measure has
      yet been developed.

PMID- 11330754
TI  - Mitral valve repair in a predominantly rheumatic population. Long-term results.
AB  - Valve repair in rheumatic patients poses special problems due to valve deformity
      and mixed lesions. We present our experience from January 1988 through June 1999,
      in this retrospective study of 818 patients (377 males). The mean age was 22.8 +/
      11.3 years (range, 2 to 70 years). The cause of mitral regurgitation was
      rheumatic in 718 (88%) patients, congenital in 51, myxomatous in 34, infective in
      7, and ischemic in 8. Most patients (64%) were in New York Heart Association
      functional class III or IV. Congestive heart failure was present in 116 patients
      (14%). Reparative procedures included posterior collar annuloplasty (n=710),
      commissurotomy (n=482), cusp-level chordal shortening (n=237), cusp thinning
      (n=222), cleft suture (n= 166), and cusp excision/plication (n=42). Operative
      mortality was 4% (32 patients). Preoperative left ventricular dysfunction,
      presence of congestive heart failure, and advanced functional class were
      associated with greater mortality. Follow-up ranged from 1 to 144 months (mean,
      44.9 +/- 33.2 months) and was 96% complete. Most survivors (70%) had no or
      trivial mitral regurgitation. Forty patients required reoperation for valve
      dysfunction. There were 23 (2.8%) late deaths. Actuarial, reoperation-free, and
      event-free survival at 11 years were 92.6% +/- 1.0%, 65.0% +/- 10%, and 38% +/-
      6.0%, respectively Among the survivors, 85% were in New York Heart Association
      functional class I. We conclude that mitral valve repair in rheumatic patients,
      using current techniques, can effectively correct hemodynamic and functional
      abnormalities with satisfactory results.

PMID- 11330756
TI  - Assessment of a low-intensity cardiac rehabilitation programme using the six
      minute walk test.
AB  - OBJECTIVE: To examine the utility of the six-minute walk test (6'WT), in
      assessing the effectiveness of a six-week cardiac rehabilitation programme, of
      which exercise training was an integral part. SETTING: Royal Liverpool and Broad
      Green Hospitals Rehabilitation Unit. DESIGN: Two hundred and thirty-nine
      consecutive patients referred for cardiac rehabilitation were allocated to one of
      two groups. In group A 209 entered and 159 completed the usual rehabilitation
      programme whilst group B patients (n = 30) acted as a control by deferring entry
      to the programme for six weeks, continuing only activities of daily living.
      OUTCOME MEASURES: Both groups were assessed using the 6'WT, peak expiratory flow
      rate (PEFR) and isometric grip strength at enrolment and six weeks. RESULTS: At
      baseline, groups A and B were demographically identical without significant
      differences in terms of 6'WT, PEFR or grip strength. Following the study period,
      group A showed a significant increase in 6'WT from 314.7 +/- 76.2 to 377.3 +/-
      78.6 m, in PEFR from 406.9 +/- 115.9 to 437.8 +/- 118.6 litres per minute and in
      grip strength from 28.8 +/- 9.31 to 30.3 +/- 8.93 kg, all p < 0.001. There were
      no significant changes in group B. CONCLUSIONS: The 6'WT proved to be a simple
      and effective measurement of functional capacity in patients performing cardiac
      rehabilitation. The clinical programme investigated successfully increased
      patients' functional capacity as assessed by the 6'WT. Significant improvement in
      PEFR and grip strength was also demonstrated, compared with a control population.

PMID- 11330757
TI  - Physical fitness training for wheelchair ambulation by the arm crank propulsion
      technique.
AB  - OBJECTIVE: To observe the effect of endurance training on novice users of an arm
      propelled three-wheeled chair (APTWC), powered by asynchronous arm crank
      propulsion, in actual locomotive conditions. STUDY DESIGN: A continuous endurance
      training programme was administered by instructing subjects to propel themselves
      at free chosen speed (FCS) for 15 minutes, twice daily. Data were collected at
      two-week intervals consecutively and this was continued until the maximum
      beneficial effect was achieved. SETTING: The study was conducted in outdoor
      settings similar to those the users encountered in their everyday life. SUBJECTS:
      Twelve male paraplegics (below T10), age 30.5 +/- 8.59 years, weight 41.75 kg (+/
      5.76) recommended to use the APTWC as an ambulatory device. INTERVENTION: The
      propulsion speed (metres per minute), peak heart rate (beats per minute) and
      oxygen uptake (litres per minute) were measured in consecutive sessions at two
      week intervals. Physiological cost index (beats m(-1)), oxygen consumption (ml
      kg(-1) min(-1)) and oxygen cost (ml kg(-1) m(-1)) were derived to assess fitness
      level. RESULTS: Significant changes were observed in the variables following
      endurance training for 12 weeks. The propulsion speed increased considerably and
      the cardiorespiratory parameters were found to be reduced. One-way analysis of
      variance was done for each parameter separately for seven sets of readings taken
      to assess the overall change over the study period of 12 weeks. The F-ratios were
      found to be significant (p < 0.01) in each case, except for body weight and
      oxygen uptake. The pairwise comparison of the biweekly results of the parameters
      which showed an overall significant change over the study period revealed that
      after the first two weeks there was considerable change (p < 0.01) for all the
      parameters. The trend was upward for speed and downward for the other
      cardiovascular stress parameters. These trends continued until the 10th week
      showing significant change, after which the values become stable as was revealed
      by thestatistical tests (p > 0.05). The percentage difference in the mean values
      from the initial stage (before training) to the 12th week ranged from 10.44% in
      the case of heart rate to 69.70% in the case of propulsion speed. CONCLUSION:
      Self-ambulation at free chosen speed regularly for 10-12 weeks provides
      efficiency and improves fitness status required for wheelchairs driven by an
      asynchronous arm crank propulsion technique and no special exercise programme is
      required.

PMID- 11330758
TI  - Fine motor assessment in chronic wrist pain: the role of adapted motor control.
AB  - OBJECTIVE: To show whether a difference in fine motor control exists between
      patients with chronic, undiagnosed wrist pain (CUWP) and healthy controls.
      Furthermore, a method to assess fine motor function of the wrist is evaluated.
      DESIGN: A case-control study. SETTING: The Academic Medical Center in Amsterdam,
      the Netherlands. SUBJECTS: Twenty-seven CUWP patients were compared with 50
      healthy control subjects. INTERVENTIONS: Subjects performed horizontal stroke
      patterns on a digital writing tablet connected to a computer. The control
      subjects were tested twice to obtain test-retest reliability. A visual analogue
      scale was used to assess subjective pain. MAIN OUTCOME MEASURES: Fluency of
      movement and average velocity were measured. Intraclass correlation, ANOVA
      repeated measures statistics and Pearson correlation were calculated. RESULTS:
      There is a significant difference in fluency of motion between patients and
      controls, possibly due to a disturbed motor control, since there is no
      relationship between pain and test score, nor do CUWP patients have any
      abnormality in the wrist that can explain the disturbance in motor function. The
      test method is reliable (ICC = 0.78) and valid. CONCLUSIONS: The disturbed fine
      motor control in CUWP patients is suggested to maintain chronic wrist pain
      through 'strain injury, causing' pain evasive adaptation of the motor control
      system. This might lead to new perspectives regarding treatment of CUWP patients.

PMID- 11330759
TI  - Walking ability as a measure of treatment effect in early rheumatoid arthritis.
AB  - OBJECTIVE: To assess the clinical usefulness of a prototype walkmat system in
      patients with early rheumatoid arthritis (RA). SUBJECTS: Twenty-four subjects
      with early RA and symptomatic forefoot disease requiring therapy with second-line
      drugs were recruited. DESIGN: Each subject underwent clinical assessment together
      with gait analysis on the contact sensitive walkmat system and Kistler forceplate
      before and after six months of treatment with second-line drugs. Two subjects
      were lost to follow-up. RESULTS: There was the expected improvement in disease
      activity in response to therapy. Significant differences were also demonstrated
      in defined gait parameters that indicated improved weight-bearing and enhanced
      forefoot propulsion. CONCLUSION: Medical therapy improved walking ability in
      patients with RA and the walkmat system provided a useful adjunct to existing
      outcome measures in the assessment of lower limb function.

PMID- 11330760
TI  - Translation and adaptation of a questionnaire to assess the group processes of
      rehabilitation team conferences.
AB  - OBJECTIVE: To investigate the internal consistency, the domain structure and the
      influence of social desirability with regard to a questionnaire translated and
      adapted to assess the quality of rehabilitation team conferences in the
      Netherlands. STUDY DESIGN: A questionnaire to determine group decision-making
      processes was translated and adapted to rehabilitation and completed by 44
      rehabilitation professionals. RESULTS: The internal consistency of the domains
      Personal participation, Negative socio-emotional behaviour, Result satisfaction
      and Process satisfaction was found to be satisfactory (Cronbach's alpha ranges
      from 0.70 to 0.84). The domain structure is confirmed by item-total and item-rest
      correlations. From the original English questionnaire, one question concerning
      the domain Personal participation was omitted. The domain Informal leadership has
      been deleted from the questionnaire, because informal leadership is not an issue
      in a situation in which the Chairman is already known. Response to the
      questionnaire did not seem to be biased by social desirability. CONCLUSION: The
      translated and adapted questionnaire can be used to assess the group processes of
      rehabilitation team conferences. Results from the literature concerning the
      original questionnaire suggest that the translated and adapted questionnaire
      might be able to detect changes in the group process of rehabilitation team
      conferences.

PMID- 11330761
TI  - A comparison of three measures of progress in early lower limb amputee
      rehabilitation.
AB  - OBJECTIVE: To assess the responsiveness to change and validity of three
      established outcome measures in relation to early lower limb vascular amputee
      rehabilitation: the Functional Independence Measure (FIM), the Office of
      Population Censuses and Surveys Scale (OPCS) and the Amputee Activity Score
      (AAS). DESIGN: Prospective observational study. SETTING: Inpatient amputee
      rehabilitation unit. SUBJECTS: Fifty-one consecutive patients admitted for
      rehabilitation following lower limb amputation for vascular disease. PROCEDURE:
      To study the responsiveness to change differences between total scores and
      between subsection scores at different times were analysed. To assess validity,
      comparisons of the total scores of the measures were made with each other, and
      the total scores for each measure were compared with other outcomes. RESULTS:
      Complete scores were obtained on 34 subjects. All measures showed significant
      change between admission and discharge (p < 0.00001) but only the AAS showed
      change between discharge and follow-up (p < 0.0001). Subsection analysis revealed
      expected improvements in mobility. During the inpatient stage progress was also
      detected in certain activities of daily living in the FIM and OPCS. The measures
      correlated with each other (p < 0.001). All of the measures' admission scores
      correlated with duration of stay (OPCS p < 0.005, AAS p < 0.006, FIM p < 0.009)
      and admission OPCS also correlated with discharge placement (p < 0.036).
      CONCLUSION: The FIM and OPCS are suitable for the inpatient stage but the AAS
      would appear to be the best measure at time of discharge and thereafter, and
      further studies are justified.

PMID- 11330762
TI  - Weight-bearing, pain and walking velocity during primary transtibial amputee
      rehabilitation.
AB  - OBJECTIVE: To explore the relationships between weight-bearing, pain and walking
      velocity in the first four weeks of prosthetic training. SUBJECTS: Consecutively
      referred transtibial amputees (n = 27). DESIGN: Longitudinal study. SETTING:
      Inpatient rehabilitation centre. INTERVENTIONS: Measurements of static weight
      bearing (SWB), perceived pain during the SWB test and self-selected walking
      velocity (VEL) were taken at entry, and at four weeks into the prosthetic
      training programme. Path analysis was conducted using a series of linear
      regression analyses to determine predictors of walking velocity at week 4.
      RESULTS: Significant improvements from week 1 to week 4 were found in SWB,
      reported pain and velocity. SWB at week 4, when coupled with age, predicted 66%
      of the variance in walking velocity at week 4. Pain did not directly predict
      velocity. However, SWB at entry and perceived pain at week 4 predicted 56% of the
      variance in SWB at week 4. CONCLUSIONS: These analyses suggested a model in which
      SWB and age were both significantly related to velocity, and further, that pain
      played a role in velocity through a relationship mediated by its direct effect on
      SWB. Unlike age, SWB is a predictor of velocity that might be altered through
      pain reduction, wound-healing and rehabilitative interventions.

PMID- 11330763
TI  - Cross-cultural validation of the London Handicap Scale in Hong Kong Chinese.
AB  - STUDY OBJECTIVE: To investigate the cross-cultural validity of London Handicap
      Scale in Hong Kong Chinese. DESIGN: Ratings of the utility of 10 hypothetical
      health scenarios were given by groups of HK Chinese subjects. Measured scores
      were compared with calculated scores from published scale weights of London
      Handicap Scale, which were based on utility ratings made by UK subjects. SETTING:
      A rehabilitation hospital in Hong Kong. SUBJECTS: A total of 164 HK Chinese,
      comprising doctors, medical students, nonmedical hospital staff, geriatric day
      hospital stroke and nonstroke patients, community day-care centre elderly, old
      age hostel elderly, young disabled inpatients and young community-dwelling
      disabled citizens. MAIN RESULTS: There was a close correlation between the mean
      scores of HK subjects and the calculated scores derived from the published UK
      scale weights, apart from one scenario (Pearson's correlation coefficient r =
      0.87 p = 0.001). The correlations were high for all subgroups, between which
      there was good consensus. Measured utilities were significantly different between
      subgroups for only one scenario. For this scenario of moderate to severe handicap
      in mobility, physical dependence, occupation and social integration, but with
      excellent orientation and economic self sufficiency: (1) older age groups gave
      better scores than younger age groups (p < 0.0005); (2) subjects with poor
      subjective health status gave better scores than those with good subjective
      health status (p = 0.002); (3) subjects related to the medical or hospital field,
      i.e. doctors, medical students and nonmedical hospital staff, gave worse scores
      than other subject groups (p < 0.0005). CONCLUSION: The concept of handicap
      applies across cultures. Perception of severity of selected real life handicap
      scenarios by HK Chinese were well estimated using scale weights from UK
      populations developed for the London Handicap Scale. Significant differences in
      perception of certain handicap scenarios by different population subgroups
      deserve further study.

PMID- 11330764
TI  - Do associated reactions in the upper limb after stroke contribute to contracture
      formation?
AB  - OBJECTIVE: To establish (1) whether associated reactions could contribute to
      contracture formation and (2) whether the presence of spasticity was essential
      for their expression, after stroke. SUBJECTS: Subjects were 24 hemiparetics
      within 13 months of a stroke, unselected for contracture or spasticity. MAIN
      OUTCOME MEASURES: Associated reactions were identified by the presence of muscle
      activity in the affected biceps brachii and quantified as the amount of affected
      elbow flexor torque produced during a moderate contraction of either the
      contralateral biceps brachii or the contralateral quadriceps muscles. Contracture
      was measured as loss of elbow joint range of motion and spasticity as the
      presence of abnormal reflex activity. RESULTS: Associated reactions were present
      in at least one testing condition in seven subjects. During contractions of the
      contralateral biceps brachii, the median amount of elbow flexor torque produced
      was 0.39 (interquartile range, IQR 2.5) Nm while during contractions of the
      contralateral quadriceps muscle it was 0.19 (IQR 1.6) Nm. Associated reactions
      were not associated with contracture (p = 0.39) which was present in over half of
      the subjects. The incidence of associated reactions was about the same as that of
      spasticity, but the two were not related (p = 0.61). CONCLUSIONS: Even though
      associated reactions were present in 29% of the subjects during moderate
      contraction of the contralateral muscles, they were not large, nor were they
      associated with contracture or spasticity, suggesting that this phenomenon is not
      usually a major problem for everyday function after stroke.

PMID- 11330765
TI  - Quantifying associated reactions in the paretic arm in stroke and their
      relationship to spasticity.
AB  - OBJECTIVES: (1) To present a measurement protocol for assessing associated
      reactions (AR) in the paretic arm and (2) to use it to investigate the pattern of
      AR and its association with spasticity. SETTING: Inpatient rehabilitation unit.
      DESIGN: Associated reactions in 49 adults with stroke were measured in terms of
      force generated, electrical muscle activity and wrist movement in the paretic arm
      using hand dynamometry, surface electromyography and electrogoniometry
      respectively. Simultaneous recording of the effort used to elicit the associated
      reaction was made using a second hand dynamometer. The magnitude and persistence
      of AR was compared with the clinical assessment of spasticity (using the modified
      Ashworth Scale, MAS). RESULTS: There was poor correlation between peak AR and
      MAS, suggesting that AR are not confined to patients with severe spasticity. Co
      activation of forearm flexors and extensors was evident during the AR. AR
      fluctuated during a single period of effort in some patients. Only 12 out of 31
      patients who maintained uniform effort over the measurement period produced a
      uniform AR. AR often persisted for some time after effort had ceased. Eight were
      classified as minimal (median AR 0.23 N), 25 as mild (median AR 2.7 N), 11 as
      moderate (median AR 6.4 N) and 3 as severe (median AR 11.0 N). AR tended to
      persist in patients with higher MAS although this result was not statistically
      significant. CONCLUSION: The magnitude, profile and persistence of AR varied
      considerably between individuals. Associated reactions were present in people
      with minimal spasticity. As this technique allows the magnitude of AR to be
      quantified in relation to effort it has the potential to be a useful outcome
      measure in clinical trials evaluating the treatments (e.g. physiotherapy)
      directed at reducing associated reactions.

PMID- 11330766
TI  - What is the association between the different components of stroke rehabilitation
      and health outcomes?
AB  - OBJECTIVES: To describe the rehabilitation input stroke patients received from
      health professionals during the early post stroke period and to explore possible
      associations between health outcomes and these rehabilitation inputs. DESIGN:
      Community-based study with prospective identification of stroke patients from a
      random sample of 24 general practices stratified by geographical area and
      practice size. SETTING: Ayrshire and Arran Health Board area, West of Scotland.
      INTERVENTIONS: All physiotherapy, occupational therapy, dietetics, podiatry,
      speech and language therapy and community nursing inputs given to stroke patients
      in the course of normal treatment were recorded. OUTCOME MEASURES: Barthel Index
      and Medical Outcomes Study Short Form-36 (SF-36). Both recorded at one, three and
      six months post stroke. RESULTS: Of the 152 people providing data, more had
      received physiotherapy than any other rehabilitation input at all three follow
      ups (81%, 47%, 39%), with occupational therapy being the next most common service
      (65%, 44%, 25%). Amount of rehabilitation input was significantly negatively
      correlated with health outcomes measured at each discrete time point: those
      patients with the poorest outcomes received greatest input. However, regression
      analysis of change in outcome scores showed that increasing amounts of
      rehabilitation input were significantly associated with a reduction in
      disability, particularly between one and three months post stroke. CONCLUSIONS:
      Not only have we shown that those stroke patients with poorest outcomes received
      most rehabilitation input, but, from analysis of the individual rehabilitation
      inputs, we have identified some rehabilitation inputs that significantly predict
      improved outcomes. This suggests that there would be merit in further
      investigation of these associations.

PMID- 11330767
TI  - Functional electrical stimulation by means of the 'Ness Handmaster Orthosis' in
      chronic stroke patients: an exploratory study.
AB  - OBJECTIVE: To gain experience with 'Ness Handmaster Orthosis' treatment in
      chronic stroke patients, to identify suitable patients, and to study the effects
      of treatment. DESIGN: Exploratory, uncontrolled trial with measurement of motor
      functions and muscle tone of the upper extremity prior to, during, upon
      completion, and six weeks after a treatment period. SETTING: A rehabilitation
      centre in the Netherlands. SUBJECTS: Eighteen chronic stroke patients (more than
      six months post stroke), who exhibited upper extremity dysfunction due to spastic
      paresis. INTERVENTION: A 10-week therapy programme of functional electrical
      stimulation by means of the 'Ness Handmaster Orthosis'. RESULTS: The results of
      15 patients were available for analysis. The differences in motor score and
      muscle tone before and at the end of treatment were statistically significant (p
      = 0.008 and 0.021, respectively). The follow-up measurements showed that the
      effects on motor functions and muscle tone decreased after therapy completion.
      Stratification of the patients in two subgroups indicated that patients with
      initial high motor scores benefited most during the intervention period.
      CONCLUSION: The present study suggests that Handmaster treatment possesses
      therapeutic opportunities in chronic stroke patients with spastic paresis of the
      upper extremity.

PMID- 11330768
TI  - The internal consistency and validity of the Self-Assessment Parkinson's Disease
      Disability Scale.
AB  - OBJECTIVE: To test the consistency and validity of the Self-assessment
      Parkinson's Disease Disability Scale in patients with Parkinson's disease living
      at home. DESIGN: Patients with Parkinson's disease responded to a set of
      questionnaires. In addition, an observation of the performance of daily
      activities was carried out on a subgroup. SETTING AND SUBJECTS: Patients with
      Parkinson's disease living at home (n = 142). MEASURES: The Self-assessment
      Parkinson's Disease Disability Scale (SPDDS), the Hoehn & Yahr Rating Scale
      (H&Y), and the Sickness Impact Profile (SIP68). The observation concerned nine
      activities that correspond to items of the SPDDS questionnaire. RESULTS: Internal
      consistency of the SPDDS was very high (Cronbach's alpha = 0.97; reliability rho
      = 0.97). The items of the SPDDS are hierarchical (Loevinger's H = 0.64): patients
      had least difficulty with 'washing' and 'brushing teeth' and most difficulty with
      'turning in bed', 'travelling by public transport' and 'writing a letter'.
      Validity of the SPDDS was good: the relationship between the SPDDS questionnaire
      and the H&Y rating scale, the SIP68 and the results of the observation was strong
      and significant. CONCLUSION: The SPDDS is a unidimensional instrument measuring
      disabilities in Parkinson's disease patients living at home.

PMID- 11330769
TI  - Medical women -- towards full integration? An analysis of the specialty choices
      made by two cohorts of Norwegian doctors.
AB  - In Norway, as in most Western countries, doctors' choice of specialty has been
      strongly gendered. Female physicians have tended both to specialise to a lesser
      degree and to enter other specialties than male colleagues. In spite of the
      increase of women in medicine, previous studies have not managed to show any
      changes in this pattern. Comparing data from two cohorts of Norwegian doctors,
      authorised in 1970-73 and 1980-83 respectively, this article demonstrates that
      changes are in fact taking place. The changes are, however, not unequivocal.
      Firstly, women in these cohorts specialise to a very high degree and just as much
      as their male colleagues. Secondly, women doctors of the 1980s cohort spread
      their choice of specialisation over more fields than their predecessors did. They
      have, for example, started to enter surgery, although still not as often as men.
      Thirdly, proportionally more doctors of the 1980s cohort than the 1970s cohort
      have chosen general practice as their main specialty, and this applies to both
      women and men. Fourthly, there are tendencies towards an increasing concentration
      of women in some disciplines such as obstetrics and gynaecology, as well as
      paediatrics. These changes in doctors' pattern of specialisation are discussed as
      consequences of socially shaped individual preferences, structural aspects of the
      Norwegian health system and the existence of gendered closure mechanisms within
      specific medical fields. Although the medical profession still appears as a
      gender differentiated community, the article gives a more dynamic and in some
      respects a more optimistic picture than earlier studies.

PMID- 11330770
TI  - Is there a menopausal syndrome? Menopausal status and symptoms across
      racial/ethnic groups.
AB  - In recent years, research on menopausal symptomalogy has focused on identifying
      symptom groupings experienced by women as they progress from premenopausal to
      postmenopausal status. However, most of these studies have been conducted among
      Caucasian women from western cultures. This leaves open the question of whether
      the findings from these studies can be extended to women of other racial/ethnic
      groups or cultures. Furthermore, many of the previous studies have been conducted
      on relatively small samples. This paper addresses the diversity of the menopause
      experience by comparing symptom reporting in a large cross-sectional survey of
      women aged 40-55 years among racial/ethnic groups of women in the United States
      (Caucasian, African-American, Chinese, Japanese, and Hispanic). Evaluation of the
      extent to which symptoms group together and consistently relate to menopausal
      status across these five samples provides evidence for or against a universal
      menopausal syndrome. The specific research questions addressed in this paper are:
      (1) How does the factor structure of symptoms among mid-aged women compare across
      racial/ethnic groups? (2) Is symptom reporting related to race/ethnicity or
      menopausal status? and (3) Does the relation between menopausal status and
      symptoms vary across racial/ethnic groups? Analyses are based on 14,906 women who
      participated in the multi-ethnic, multi-race, multi-site study of mid-aged women
      called the Study of Women's Health Across the Nation (SWAN). Study participants
      completed a 15-min telephone or in-person interview that contained questions on a
      variety of health-related topics. Items of interest for these analyses include
      symptoms, menstrual history (to assess menopausal status), health status, and
      sociodemographics. Factor analysis results showed that across all five
      racial/ethnic groups, two consistent factors emerged; one consisting of clearly
      menopausal symptoms -- hot flashes and night sweats -- and the other consisting
      of psychological and psychosomatic symptoms. Results of regression analyses
      showed racial/ethnic differences in symptom reporting, as well as differences by
      menopausal status. Controlling for age, education, health, and economic strain,
      Caucasian women reported significantly more psychosomatic symptoms than other
      racial/ethnic groups. African-American women reported significantly more
      vasomotor symptoms. Perimenopausal women, hormone users, and women who had a
      surgical menopause reported significantly more vasomotor symptoms. All of these
      groups, plus postmenopausal women, reported significantly more vasomotor symptoms
      than premenopausal women. The pattern of results argues against a universal
      menopausal syndrome consisting of a variety of vasomotor and psychological
      symptoms.

PMID- 11330771
TI  - The impact of marital status on cancer survival.
AB  - Marital differentials in survival from 12 common types of cancer are assessed by
      estimating a mixed additive multiplicative hazard regression model on the basis
      of individual register and census data for the whole Norwegian population. These
      data cover the period 1960-91 and include more than 100,000 cancer deaths. The
      data and method make it possible to take into account the marital mortality
      differentialsin the absence of cancer. The excess all-cause mortality among
      cancer patients compared with similar persons without a cancer diagnosis is, on
      the whole, more than 15% higher for never-married men, never-married women and
      divorced men, than for the married of the same sex. Other previously married have
      an excess mortality elevated by about 7%. This protective effect of marriage is
      not due to stage, which is controlled for. The possible importance of treatment
      and host factors is discussed.

PMID- 11330772
TI  - Subjective well-being and severe motor impairments: the Tetrafigap survey on the
      long-term outcome of tetraplegic spinal cord injured persons.
AB  - The purpose of the research described in this article is to study the effects of
      severe motor impairments on a person's well-being, by attempting to throw light
      upon the inconsistencies found in the previous literature, which are due to
      problems of a conceptual and methodological nature. The data were gathered during
      the Tetrafigap survey on the long-term outcome of tetraplegic persons in France.
      This survey involved 1668 tetraplegic spinal cord injured people. We examine the
      relationships between the overall assessment of well-being as expressed by the
      people interviewed, and a range of clinical, social and psycho-social factors. A
      progressive approach, along with the use of adjustments via linear regressions,
      has allowed us to identify certain confounding factors, and to analyse the
      respective effects of the different types of variables studied. Thus current age,
      the age at which the impairment occurred and having or not having a professional
      activity do not have any direct links with the assessment of well-being, whereas
      the existence of pain and the subjective assessment of one's own independence and
      of the severity of one's disability are predictive factors. The functional
      independence indicators are only linked to well-being when they relate to
      situations in which the dependence creates embarrassment due to socio-cultural
      taboos. The loss of autonomy only affects well-being in as much as it imposes
      limits to social activity, whether they be relational or occupational. Living as
      a couple is a negative predictive factor if the couple were together prior to the
      impairment occurring. The overall results demonstrate the importance of moving
      beyond any conception of the impact of the impairments on well-being that is too
      exclusively focused on the individual, and of integrating the socio-cultural
      meanings of handicap situations and the dynamics of the interactions which take
      place therein.

PMID- 11330773
TI  - Compression or expansion of morbidity? Trends in healthy-life expectancy in the
      elderly Austrian population between 1978 and 1998.
AB  - The aim of our study is to test the theories of compression or expansion of
      morbidity on the basis of data on the elderly population of Austria. Our data
      come from four microcensus surveys for the years 1978, 1983, 1991, and 1998. We
      use self-perceived health ratings to calculate healthy-life expectancy for the
      elderly population aged 60-89. Because our data are based on four cross-sectional
      surveys, we devote the first part of the paper to the consequences of possible
      sampling and non-sampling errors in our analysis of time trends. We come to the
      conclusion that, although the absolute number of years lived in good health may
      be overestimated, the time trend in healthy-life expectancy over the 20 years
      most probably is unbiased. The second part of the paper describes trends in
      healthy-life expectancy for the Austrian population. Our results suggest that
      both healthy-life expectancy and the ratio of healthy years to life expectancy
      increased between 1978 and 1998. Thus, in Austria ill health seems to be more and
      more compressed into the later years of life. Contrary to Fries's hypothesis,
      however, life expectancy does not seem to be approaching a maximum average life
      span in Austria, as mortality rates at older ages have been continuously
      decreasing over the last 20 years.

PMID- 11330774
TI  - Real world pharmacy: assessing the quality of private pharmacy practice in the
      Lao People's Democratic Republic.
AB  - The private sector is a dominant actor in the provision of pharmaceuticals,
      particularly in developing countries. Private provision of drugs has been
      associated with risks regarding availability, affordability, rational use and
      drug quality. Ensuring an effective regulatory framework is therefore a major
      challenge for governments, yet the capacity of regulatory authorities is often
      outstripped by private sector growth. In the Lao People's Democratic Republic
      (Lao P.D.R.), a poor, landlocked country in South East Asia, the private
      provision of drugs has increased dramatically since the liberalisation of the
      economy in the late 1980s. This paper aims to describe the quality of the private
      pharmacy services in the Savannakhet province of Lao P.D.R. In order to do this,
      a monitoring instrument which serves to make the concept of Good Pharmacy
      Practice (GPP) operational was developed and applied to a sample of pharmacies.
      Service quality, as measured by three facility-specific indicators, showed a
      tendency to be lower in the most distant districts. Poor dispensing practices
      were manifest by a lack of information about drugs sold in 59% of cases, drugs
      not being labelled in 47% and different drugs being mixed in the same package in
      26% of cases. The prices of four sample drugs were slightly higher in the remote
      districts. A 10-fold price difference for the same drug was recorded in one
      district. After reporting the findings, the paper discusses the possible
      influence of district and pharmacy variables on the quality of services, and goes
      on to discuss the price differences. It is concluded that further government
      interventions are needed in order to improve the quality of services and to focus
      regulatory action on a limited number of aspects, to ensure that drugs can be
      traced before trying to establish a comprehensive regulatory system.

PMID- 11330775
TI  - Psychophysiological effects of temporary alternative employment.
AB  - Twenty-one participants in a mobilising labour market project offering temporary,
      alternative employment in Sweden were followed longitudinally for one year,
      including a six month post-participation follow-up period. Earlier analyses of
      self-rated psychosocial data have indicated consistent improvements in mental
      health and quality of life. In the present study, however, a significant rise in
      serum prolactin, plus decreased dehydro-epiandro-sterone sulphate levels and
      tendencies towards increased alanine aminotransferase, gamma-glutamyl transferase
      and diastolic blood pressure, seem to disconfirm the hypothesis that biological
      markers of psychosocial health would improve in a similar fashion. It is
      speculated that this apparent inconsistency could be part of a protective
      adaptation to long-term unemployment similar to the cocooning tendencies in
      maternal behaviour. Specifically, we argue that this could protect against the
      stress of being in an uncontrollable and 'helpless' situation by facilitating a
      re-focusing on more private matters as opposed to 'hopeless' job seeking. While
      being potentially detrimental for people with fair chances on the labour market,
      it is possible that such an adaptation may be helpful for more vulnerable groups.

PMID- 11330776
TI  - Violence towards health care staff and possible effects on the quality of patient
      care.
AB  - Much of the research on violence in the health care sector has focused on the
      immediate and long-term effects of patient violence on staff victims. There is a
      lack of studies, however, examining whether individual reactions to violent
      episodes, such as anger and increased fear in one's work, have any measurable
      effect on staff behaviour toward their patients, and ultimately on the quality of
      patient care. The aim of the present study was to investigate whether an
      association exists between staff experiences with violence and patient-rated
      quality of patient care. A theoretical model was presented, suggesting that
      violence or threats experienced by health care staff have a negative effect on
      the quality of health care services offered, as measured by patients. In
      addition, it was theorised that there would be an association between staff work
      environment and staff reports of violence. Six questionnaire studies, three
      concerning hospital staff's views of their work environment and three dealing
      with patients' perceptions of the quality of care, provided the data for
      evaluating the model. Work environment and quality of care studies were carried
      out simultaneously at a single hospital in 1994, 1995, and again in 1997.
      Regression analysis was used to see which combination of work environment and
      quality of care variables would best predict a positive overall grade for quality
      of care from the patient perspective. Violence entered consistently as an
      important predictor into each of the three best regression equations for 1994,
      1995, and 1997, respectively. The results of this analysis suggest that the
      violence experienced by health care staff is associated with lower patient
      ratings of the quality of care. The study indicates that violence is not merely
      an occupational health issue, but may have significant implications for the
      quality of care provided.

PMID- 11330777
TI  - Health and cultural factors associated with enrolment in basic education: a study
      in rural Ghana.
AB  - This inter-disciplinary study compares the health status of school-age children
      in Ghana, both enrolled and non-enrolled, and examines these results within a
      wider socio-economic and socio-cultural context including kinship and livelihood.
      Children matched for age and sex who were not enrolled in Primary School were
      significantly shorter and more stunted than enrolled children were, and 70% of
      all Primary school-age children were anaemic. Young children from farming
      communities were significantly more undernourished than children from fishing
      communities. Adolescent non-enrolled boys were more heavily infected with
      Schistosoma haematobium, and were more likely to be anaemic than enrolled
      adolescent boys. The data indicate how health and health related factors may
      influence and affect enrolment and how socio-economic indicators, livelihood, and
      kinship may also constrain enrolment and, in turn, affect child health. This
      study sheds light on the complex factors that may influence enrolment in
      education and provides novel data on the similarities and differences between the
      health of enrolled and non-enrolled children in rural Ghana.

PMID- 11330778
TI  - Socioeconomic differences in leisure-time physical activity: the role of social
      participation and social capital in shaping health related behaviour.
AB  - Several studies have shown socioeconomic differences in leisure-time physical
      activity. One explanation may be socioeconomic differences in relevant
      psychosocial conditions. The Malmo Diet and Cancer Study is a prospective cohort
      study including inhabitants in Malmo, Sweden. The baseline questionnaire used in
      this cross-sectional study was completed by the 11,837 participants born 1926
      1945 in 1992-1994. Leisure-time physical activity was measured by an item
      presenting a variety of activities. These activities were aggregated into a
      summary measure of leisure-time physical activity that takes both the intensity
      and duration of each specific activity into consideration. The effects of the
      psychosocial variables on the socioeconomic differences in leisure-time physical
      activity were calculated in a multivariate logistic regression analysis. The
      quartile with the lowest degree of leisure-time physical activity was not evenly
      distributed between the socioeconomic groups. Socioeconomic differences were seen
      as odds ratios 1.5 for skilled and 1.5 for unskilled male manual workers,
      compared to the high level non-manual employees. An OR 1.6 was observed for
      female unskilled manual workers. Self-employed men and female pensioners also had
      a significantly increased risk of low leisure-time physical activity. Adjustment
      for age, country of origin and previous/current diseases had no effect on these
      SES differences. Finally, adjusting for social participation almost completely
      erased the SES differences. Among the psychosocial variables, social
      participation was the strongest predictor of low physical activity, and a strong
      predictor for socioeconomic differences in low leisure-time physical activity.
      Social participation measures the individual's social activities in, for example
      political parties and organisations. It therefore seems possible that some of the
      socioeconomic differences in leisure-time physical activity are due to differing
      social capital between socioeconomic groups.

PMID- 11330779
TI  - Future states: the axioms underlying prospective, future-oriented, health
      planning instruments.
AB  - Proscriptive planning exercises are critical to and generally accepted as
      integral to health planning at varying scales. These require specific instruments
      designed to predict future actions on the basis of present knowledge. At the
      macro-level of health economics, for example, a number of future-oriented Quality
      of Life Instruments (QL) are commonly employed. At the level of individual
      decision making, on the other hand, Advance Directives (AD's) are advanced as a
      means by which healthy individuals can assure their wishes will be carried out if
      at some future point they are incapacitated. As proscriptive tools, both
      instrument classes appear to share an axiomatic set whose individual parts have
      not been rigorously considered. This paper attempts to first identify and then
      consider a set of five axioms underlying future oriented health planning
      instruments. These axioms are then critiqued using data from a pre-test survey
      designed specifically to address their assumptions. Results appear to challenge
      the validity of the axioms underlying the proscriptive planning instruments.

PMID- 11330780
TI  - Tactics at the interface: Australian Aboriginal and Torres Strait Islander health
      managers.
AB  - Over the past thirty years in Australia, there has been a recognition of the need
      for increasing Aboriginal and Torres Strait Islander participation in the
      management of their health services as part of the strategy to improve the poor
      health of Australia's indigenous peoples. The proliferation of Aboriginal
      Community-Controlled Health Services and the vigorous advocacy of groups such as
      the National Aboriginal Community Controlled Health Organisation have
      significantly contributed to this recognition. This, combined with additional
      management opportunities in government service, has drawn attention to
      difficulties in recruiting and retaining appropriately experienced Aboriginal and
      Torres Strait Islander managers, particularly in the northern states of
      Australia.

PMID- 11330781
TI  - The political context of social inequalities and health.
AB  - This analysis reflects on the importance of political parties, and the policies
      they implement when in government, in determining the level of
      equalities/inequalities in a society, the extent of the welfare state (including
      the level of health care coverage by the state), the employment/unemployment
      rate, and the level of population health. The study looks at the impact of the
      major political traditions in the advanced OECD countries during the golden years
      of capitalism (1945-1980) -- social democratic, Christian democratic, liberal,
      and ex-fascist -- in four areas: (1) the main determinants of income
      inequalities, such as the overall distribution of income derived from capital
      versus labor, wage dispersion in the labor force, the redistributive effect of
      the welfare state, and the levels and types of employment/ unemployment; (2)
      levels of public expenditures and health care benefits coverage; (3) public
      support of services to families, such as child care and domiciliary care; and (4)
      the level of population health as measured by infant mortality rates. The results
      indicate that political traditions more committed to redistributive policies
      (both economic and social) and full-employment policies, such as the social
      democratic parties, were generally more successful in improving the health of
      populations, such as reducing infant mortality. The erroneous assumption of a
      conflict between social equity and economic efficiency, as in the liberal
      tradition, is also discussed. The study aims at filling a void in the growing
      health and social inequalities literature, which rarely touches on the importance
      of political forces in influencing inequalities. The data used in the study are
      largely from OECD health data for 1997 and 1998; the OECD statistical services;
      the comparative welfare state data set assembled by Huber, Ragin and Stephens;
      and the US Bureau of Labor Statistics.

PMID- 11330782
TI  - Radiolabeled peptides in the detection of deep venous thrombosis.
AB  - Venous thrombosis and pulmonary embolism are major clinical problems that result
      in significant morbidity and mortality. It is estimated that 600,000 cases of
      pulmonary embolism occur each year in the United States, resulting in the death
      of approximately 100,000 patients. Most of these pulmonary emboli arise from deep
      venous thrombosis (DVT). The clinical diagnosis of DVT is unreliable. Only a
      third of patients with a clinical suspicion of DVT have objective evidence of the
      disease, and half of patients with proven DVT do not have any clinical symptoms.
      Although ascending contrast venography is the present standard for the diagnosis
      of DVT, duplex ultrasonography, which is increasingly used in combination with
      color Doppler flow imaging, is accepted as a useful clinical afternative to
      contrast venography. Both contrast venography and ultrasonography are imaging
      procedures that detect changes in venous anatomy that are caused by the presence
      of an intraluminal thrombus that is sufficiently formed either to reduce vascular
      filling with contrast medium or to resist compression. However, these imaging
      procedures do not reflect the metabolic activity of the clot, and therefore, they
      may overestimate the presence of active clots. The sensitivity of ultrasonography
      is also limited by various disease-related and technical factors. An alternative
      approach to the diagnosis of acute DVT is to detect a molecular marker of acute
      DVT that is not present in old, organized DVT. Recent advances in biotechnology
      permit the use of highly specific synthetic peptide or small molecular markers,
      which are involved in the acute stages of DVT formation and can be labeled
      efficiently with 99mTc. 99mTc-apcitide, a glycoprotein (GP IIb/IIIa) receptor
      antagonist previously known as 99mTc-P280, has been approved recently by the Food
      and Drug Administration for the clinical detection of acute DVT. Two other agents
      are currently under clinical investigation: 99mTc-DMP 444, which is another GP
      IIb/IIIa receptor antagonist, and 99mTc-Fibrin-Binding Domain (FBD), a radio
      labeled fibrin-binding domain of fibronectin. Different clinical studies have
      shown a high diagnostic accuracy with these synthetic 99mTc-labeled peptides in
      the detection of acute DVT. Although further studies are needed to fully
      appreciate all of the diagnostic potential of these radiopharmaceuticals, the
      clinical introduction of 99mTcapcitide scintigraphy will certainly be helpful in
      expanding the use of nuclear medicine in a specific field in which it used to
      play a relatively marginal role.

PMID- 11330783
TI  - Radionuclide venography and labeled platelets in deep venous thrombosis.
AB  - 99mTc-labeled macroaggregated albumin, 99mTc-labeled red blood cell, and 99mTc
      human serum albumin blood pool venography are simple, noninvasive imaging
      procedures that provide indirect evidence of deep vein thrombosis. These
      techniques rely on alterations in the normal venous anatomy. They do not
      determine the cause of venous obstruction and/or altered anatomy and cannot
      differentiate between acute and chronic deep venous thrombosis. In vitro labeled
      platelet scintigraphy provides direct evidence of active or acute thrombosis.
      Unfortunately, this technique requires a labor-intensive, lengthy labeling
      process and has a high number of false-negative results in patients who receive
      heparin therapy.

PMID- 11330784
TI  - Assessment of peripheral arterial vascular disease with radionuclide techniques.
AB  - Various radioisotopic imaging techniques for noninvasive detection of vessel
      stenosis and for functional investigation of reduced blood flow and follow-up
      have been developed during the last decade in peripheral vascular disease (PVD),
      with the aim of replacing invasive techniques and complementing standardized
      methods. Radionuclide assessment of PVD is divided into 2 major groups: imaging
      of perfusion and metabolic investigations. The measurement of arterial blood flow
      and muscle perfusion is intended to show the morphology, to evaluate the
      functional consequences of PVD, and to quantify the latter. The application of
      radiolabeled tracers was developed as a noninvasive alternative to angiography in
      morphologic imaging. Treadmill testing has been used to assess the functional
      effects of reduced blood flow in PVD where the onset of pain indicates the stage
      of disease, but the results can be confused by other symptoms. Scintigraphic
      measurement of muscle perfusion should detect insufficient nutritional blood flow
      in peripheral muscle and thus have a higher specificity for PVD than treadmill
      testing alone. Although there are very promising theoretical and experimental
      data in animals, the clinical use of radionuclide investigations is limited by
      different technical problems, such as methodologic differentiation between skin
      and muscle perfusion, the lack of controlled and prospective studies, and
      incomplete correlation with other standardized routine techniques. Among the
      great number of radioisotopic metabolic imaging techniques, only radiolabeled
      platelets and lipoproteins, to some extent, have shown a limited potential
      clinical use. Some other approaches seem to have a high potential from a
      theoretical point of view. They are limited, however, by a great number of
      problems. Correlation with sonographic or magnetic resonance imaging (MRI)
      findings may identify a potential metabolic value. Correlation with angiography
      reflecting the extent of the disease makes no sense. So far with PVD, neither
      radioisotopic perfusion studies nor metabolic imaging techniques are able to
      achieve a level of routine application or wider meaningful interpretation of the
      clinical condition of a specific patient. Competing techniques are easier to
      perform, less expensive, faster, more widely available, and do not carry the
      radiation burden. Positron emission tomography is still in its early stages of
      application, with great theoretical potential but at a high price. A great deal
      of work is still required to transform in vitro and experimental experience into
      more meaningful routine radioisotopic investigations in patients with PVD.

PMID- 11330785
TI  - Enhanced lung scan diagnosis of pulmonary embolism with the use of ancillary
      scintigraphic findings and clinical correlation.
AB  - Analysis of the Prospective Investigation of Pulmonary Embolism Diagnosis
      (PIOPED) and modified PIOPED studies has suggested that an experienced observer
      is capable of more accurate lung scan interpretation than the less experienced
      individual. This has been attributed to the use of unique Gestalt factors not
      contained in published diagnostic algorithms, which are acquired through
      extensive experience in reviewing and interpreting lung scans. How fully these
      factors can be codified and transmitted to less experienced observers is
      uncertain; however, there is a large body of published data that attempts to
      convey fine points of lung scan interpretation, including a large body of
      ancillary scintigraphic findings and a number of refinements in the application
      of diagnostic algorithms. Review of these factors will accelerate the training of
      less experienced readers. Finally, an understanding of lung scan language and an
      appreciation of clinically relevant factors, particularly pretest probability,
      will maximize the reader's ability to use the lung scan in managing patients who
      are suspected of having pulmonary embolic disease.

PMID- 11330786
TI  - Revolutionary impact of lymphoscintigraphy and intraoperative sentinel node
      mapping in the clinical practice of oncology.
AB  - Intraoperative lymphatic mapping is a rapidly emerging diagnostic approach that
      is revolutionizing the management of patients who have solid malignant tumors.
      The procedure is being performed for the most part with radiopharmaceuticals and
      vital blue dyes. It is widely believed that passive trapping of radioactive
      particles determines the sentinel lymph node (SLN) for intraoperative delineation
      of potential draining sites. In this article, we show that dendritic cells within
      the SLN actively take up and trap radioactive particles and thus define the SLN
      immunologically. The role of preoperative lymphoscintigraphy and the selection of
      the site of placement of mapping reagents for intraoperative lymphatic mapping
      are established for patients with melanoma. For patients with breast cancer, the
      role of preoperative lymphoscintigraphy is controversial. We have shown that this
      procedure can be performed with success in identifying SLN as hot spots 87% of
      the time, with 20% of the cases showing draining nodes to other basins in
      addition to or independent of the axilla. The use of preoperative
      lymphoscintigraphy for patients with breast cancer can therefore be justified.
      The selection of the site for placement of radiotracer and blue dye can vary for
      patients with breast cancer depending on the primary site of the lesion. However,
      based on data from our institution and others, the delivery of the mapping
      reagents (both radioactive tracers and blue dye) to the subareolar space may help
      to standardize breast cancer SLN mapping.

PMID- 11330787
TI  - The evolution of cerebral perfusion abnormalities in Lewy body disease:
      assessment with Tc-99m hexamethylpropylene amineoxime single photon emission
      computed tomography.

PMID- 11330788
TI  - Unilateral gallium-67 citrate uptake in mucosa-associated lymphoid tissue
      lymphoma of the parotid gland.

PMID- 11330789
TI  - Pathophysiology and diagnosis of deep venous thrombosis.
AB  - Lower-limb deep venous thrombosis (DVT) affects between 1% to 2% of hospitalized
      patients. These thrombi disrupt the vascular integrity of the lower limbs and are
      the source of emboli that kill approximately 200,000 patients each year in the
      United States. The causes of thrombosis include vessel wall damage, stasis or low
      flow, and hypercoagulability. These factors favor clot formation by disrupting
      the balance of the opposing coagulative and fibrinolytic systems. The symptoms
      and signs of venous thrombosis are caused by obstruction to venous outflow,
      vascular inflammation, or pulmonary embolization. About 70% of patients referred
      for clinically suspected venous thrombosis, however, do not have the diagnosis
      confirmed by objective testing. Among the 30% who have venous thrombosis, about
      85% have proximal vein thrombosis, and the remainder have thrombosis confined to
      the calf. Physicians cannot rely on signs and symptoms to make the diagnosis of
      DVT and must depend on imaging studies to guide treatment. Patients with proximal
      vein thrombosis who are inadequately treated have a 47% frequency of recurrent
      venous thromboembolism over 3 months. In contrast, clinically detectable
      recurrence occurs in less than 2% of patients with proximal vein thrombosis if an
      adequate anticoagulant response is achieved. Of the diagnostic procedures for
      DVT, venography is the only invasive test of proven value, and ultrasonographic
      (US) studies are the most commonly used noninvasive modaity. Other procedures are
      occasionally used to diagnose DVT, including impedance plethysmography, computed
      tomography, and magnetic resonance imaging. US examinations are noninvasive, they
      are rapidly obtained, and they can be performed serially. In symptomatic
      patients, venous US is sensitive and specific for proximal DVT; however, US is
      insensitive to calf vein thrombosis and to asymptomatic DVT occurring after
      surgery. Patients with symptoms of recurrent DVT also can present a difficult
      diagnostic problem. Only about 20% to 30% of these individuals actually have the
      disease; the rest have symptoms arising from chronic venous insufficiency or from
      any of the causes of lower extremity pain. After an acute episode, up to 50% of
      patients have compression ultrasound abnormalities for 6 months that are
      indistinguishable from the original findings of DVT. Hence, there are a
      significant number of patients and clinical circumstances in which the diagnosis
      of DVT is difficult. 99mTc-radiolabeled peptides that target the molecular
      biology of thrombosis should aid in the management of the disease, particularly
      in asymptomatic patients at high risk, in patients with recurrent symptoms, in
      patients with active DVT in the calf and/or pelvis, and in patients with
      intermediate- or low-probability lung scans.

PMID- 11330790
TI  - Purification of microcystins.
AB  - Microcystins are an increasingly important group of bioactive compounds produced
      by a number of mainly planktonic cyanobacteria. They are a family of cyclic
      heptapeptides that cause both acute and chronic toxicity. Purified microcystins
      are utilised in a range of research applications including toxicological and
      biochemical studies, development of detection systems and the investigation of
      water treatment strategies. The commercial availability of purified microcystins
      is still relatively limited and for many projects the cost of their purchase
      prohibitive. The purification of microcystins from both bloom material and
      laboratory cultures is reviewed including a discussion on extraction, separation,
      and the determination of purity and yield.

PMID- 11330791
TI  - Quantitative structure-retention and retention-activity relationships of beta
      blocking agents by micellar liquid chromatography.
AB  - Sixteen beta-blocking agents (acebutolol, alprenolol, atenolol, bisoprolol,
      carteolol, celiprolol, esmolol, labetalol, metoprolol, nadolol, oxprenolol,
      pindolol, practolol, propranolol, sotalol and timolol) showing a large range of
      hydrophobicity (octanol-water partition coefficients, log P between -0.026 and
      2.81) were subjected to micellar liquid chromatography with sodium dodecyl
      sulfate as micelle forming agent, and n-propanol as organic modifier. The
      correlation between log P and the retention factor extrapolated to a mobile phase
      free of micelles and organic modifier was investigated. The use of an
      interpolated retention factor or the retention factor for specific individual
      experimental mobile phases was however advantageous since the retention factors
      of all beta-blocking agents were measurable in the selected mobile phases. Good
      correlations with log P and with in vitro biological parameters (cellular
      permeability coefficients in Caco-2 monolayers and apparent permeability
      coefficients in rat intestinal segments) were found.

PMID- 11330792
TI  - Determination of electroactive organic acids by anion-exchange chromatography
      using a copper modified electrode.
AB  - An ion-chromatographic method combined with electrochemical detection at a copper
      based chemically modified glassy carbon electrode (Cu-GC) has been shown to
      provide a simple analytical approach for the determination of some common organic
      acids in alkaline medium. Under the optimized isocratic chromatographic
      conditions (i.e. 0.1 M NaOH plus 80 mM CH3COONa), organic acids such as gallic,
      ascorbic, gluconic, lactobionic, galacturonic and glucuronic acid could be
      separated in less than 20 min. Under constant potential amperometric detection
      (i.e. 0.55 V vs. Ag-AgCl) the Cu-GC modified electrode allowed detection limits
      between 2 and 5 pmol for all investigated organic acids while the linear dynamic
      range spanned generally over three orders of magnitude. Examples of applications
      included the separation and quantitation of some common organic acids in vinegar,
      honey and tea samples, are given.

PMID- 11330793
TI  - Theories of chromatographic efficiency applied to expanded beds.
AB  - Various quantities such as plate height (HETP), number of plates (N), axial
      dispersion coefficient (Dax) and Bodenstein number (Bo) are used to describe the
      efficiency of, and dispersion in chromatographic columns. Different quantities
      highlight different aspects of the performance. Due to the expansion of expanded
      bed columns, the information contained in some of these quantities is not the
      same for expanded beds as for packed beds. In this article the mentioned
      quantities are described and discussed both theoretically and related to
      experimental data. It is concluded that they are often used in a confusing way.
      Quantities modified to be more informative when comparing beds of different
      expansions are developed (N(EB) = N/expansion2 and HETP(EB) = HETP x bed
      expansion) and recommendations of which quantity to use in what situation are
      given.

PMID- 11330794
TI  - Separation of phenolic compounds by high-performance liquid chromatography with
      absorbance and fluorimetric detection.
AB  - Phenolic compounds including phenolic aldehydes, acids and flavonoids are
      separated by high-performance liquid chromatography (HPLC) with analysis time
      shorter than described in the literature. The use of a fluorescence detector in
      series with absorbance detector allowed increasing selectivity and sensitivity
      for the determination of catechin, vanillic acid, syringic acid, epicatechin and
      trans-resveratrol in wine samples. An optimised sample preparation method using
      liquid-liquid extraction with diethyl ether at pH 2.0 was used. The optimised
      method was applied to analyse wine samples with good results.

PMID- 11330795
TI  - Determination of capsaicin, dihydrocapsaicin, and nonivamide in self-defense
      weapons by liquid chromatography-mass spectrometry and liquid chromatography
      tandem mass spectrometry.
AB  - Sensitive and selective liquid chromatography-mass spectrometry (LC-MS) and
      liquid chromatography-tandem mass spectrometry (LC-MS-MS) methods for the
      analysis of capsaicin, dihydrocapsaicin, and nonivamide in pepper spray products
      have been developed. Chromatographic separation of the capsaicinoid analogues was
      achieved using a reversed-phase HPLC column and a stepwise gradient of methanol
      and distilled water containing 0.1% (v/v) formic acid. Identification and
      quantification of the capsaicinoids was achieved by electrospray ionization
      single-stage mass spectrometry monitoring the protonated molecules of the
      internal standard (m/z 280), capsaicin (m/z 306), dihydrocapsaicin (m/z 308), and
      nonivamide (m/z 294) or by tandem mass spectrometry monitoring the appropriate
      precursor-to-product-ion transitions. The plot of concentration versus peak area
      ratio was linear over the range of 10-750 ng/ml using LC-MS and 10-500 ng/ml
      using LC-MS-MS. However, to accurately quantify the capsaicinoids in the pepper
      spray products calibration curves between 10 and 1000 ng were constructed and fit
      using a weighted quadratic equation. Using the quadratic curve, the accuracy of
      the assay ranged from 91 to 102% for all analytes. The intra-assay precision
      (RSD) for capsaicin was 2% at 25 ng/ml, 10% at 500 ng/ml, and 3% at 800 ng/ml.
      The inter-assay precision (RSD) for capsaicin was 6% at 25 ng/ml, 6% at 500
      ng/ml, and 9% at 800 ng/ml. Similar values for inter- and intra-assay precision
      were experimentally obtained for both dihydrocapsaicin and nonivamide. The
      analysis of selected pepper spray products demonstrated that the capsaicinoid
      concentration in the products ranged from 0.7 to 40.5 microg/microl.

PMID- 11330796
TI  - High-performance liquid chromatography coupled on-line with electrospray
      ionization mass spectrometry for the simultaneous separation and identification
      of the Synechocystis PCC 6803 phycobilisome proteins.
AB  - The complete resolution of the protein components of phycobilisome from
      cyanobacterium Synechocystis 6803, together with their detection and
      determination of molecular mass, has successfully been obtained by the combined
      use of HPLC coupled on-line with electrospray ionization mass spectrometry. The
      method proposed consists of the isolation of the light-harvesting apparatus of
      cyanobacterium, by simply breaking cells in low-ionic-strength buffer, and
      subsequent injection of the total mixture of phycobilisomes into a C4 reversed
      phase column. Identification of proteins was performed by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE) of the samples collected from HPLC
      or by measuring the protein molecular mass coupling HPLC with mass spectrometry.
      The latter method allows the simultaneous separation of the phycobiliproteins,
      phycocyanin and allophycocyanin, from linker proteins and their identification,
      which due to their similar amino acid sequence and their similar hydrophobicity,
      might not be detected by denaturing SDS-PAGE. Under the experimental conditions
      used, the pigment phycobilin is not removed from the polypeptide backbone,
      determining the hydrophobicity of the phycoproteins and hence their interaction
      with the reversed-phase column as well as in determining the protein-protein
      interaction into the phycobilisome aggregation. Removal of the pigment, in fact,
      abolishes HPLC separation, emphasizing the essential role that the pigments play
      in maintaining the unusual tertiary structure of these proteins.

PMID- 11330797
TI  - Microcalorimetric studies of the interaction mechanisms between proteins and Q
      sepharose at pH near the isoelectric point (pI) effects of NaCl concentration, pH
      value, and temperature.
AB  - This study examined the interaction mechanisms of beta-lactoglobulins A and B (Lg
      A, Lg B) with an anion exchanger, Q-Sepharose at pH near the isoelectric point at
      which the proteins are expected to be electrically neutralized under various NaCl
      concentrations and temperatures by the equilibrium binding analysis and the
      adsorption enthalpy directly measured by isothermal titration calorimetry. The
      data evaluated from isotherms fitted by the Langmuirean model reveal that the
      addition of NaCl considerably reduced the binding affinities and capacities of
      both the proteins with Q-Sepharose at pH 5.2, indicating that electrostatic
      forces are dominant during the adsorption. However, the hydrophobic interaction
      seems to be involved in adsorption as well at a higher NaCl concentration, and
      the adsorption enthalpies confirm this suggestion. In addition, the effects of
      temperature on the equilibrium binding behaviors for Lg A or Lg B with Q
      Sepharose were found to be salt concentration-dependent, probably due to their
      different binding mechanisms at 0.03 M and 0.3 M NaCl. Where, at 0.3 M NaCl, the
      hydrophobic interaction plays a more pronounced role. This implication was again
      supported by the adsorption enthalpies. The presented data provide further
      insight to the interaction mechanisms between proteins and ion exchangers,
      facilitating the optimization of protein separations.

PMID- 11330798
TI  - Determination of sarin, soman and their hydrolysis products in soil by packed
      capillary liquid chromatography-electrospray mass spectrometry.
AB  - An analytical method based on aqueous ultrasonic extraction and packed capillary
      liquid chromatography-electrospray mass spectrometry (LC-ESI-MS) analysis was
      developed and compared to an existing gas chromatography(GC)-MS based method for
      the determination of sarin, soman and their hydrolysis products in contaminated
      soil. Three soils, a red clay, a tan sandy clay and a brown sandy clay loam, were
      spiked with sarin and soman and their initial hydrolysis products, isopropyl
      methylphosphonic acid and pinacolyl methylphosphonic acid, at the 10 microg/g
      level to assess recovery efficiency. Recovery of sarin and soman from the aqueous
      soil extracts was comparable to the existing analytical method, with a
      significant improvement in recovery being demonstrated for the chemical warfare
      agent hydrolysis products. Sarin and soman were recovered in the 20-90% range
      from the three soil types with aqueous extraction, while the hydrolysis products
      of these chemical warfare agents were extracted with recoveries in excess of 80%.
      The developed soil extraction and analysis method appears to be an attractive
      alternative to the GC-MS based method, since aqueous extracts containing chemical
      warfare agent hydrolysis products may be analysed directly, eliminating the need
      for additional sample handling and derivatization steps.

PMID- 11330799
TI  - Liquid chromatographic-mass spectrometric determination of post-harvest
      fungicides in citrus fruits.
AB  - Liquid chromatography (LC)-atmospheric pressure ionisation (API)-mass
      spectrometry (MS) has been used to determine residues of five fungicides in
      oranges with a minimum sample cleanup. Atmospheric pressure chemical ionisation
      (APCI) and electrospray (ES) were compared and both gave similar results in terms
      of sensitivity and structural information. The main ions were [M+H]+ for
      carbendazim, imazalil, thiophanate methyl and thiabendazole, and [M+H-C4H9NHCO]+
      for benomyl. Samples were extracted with sodium sulphate and ethyl acetate.
      Although benomyl and thiophanate methyl were transformed through the extraction
      procedure to carbendazim, the method showed good precision (<13%) and recovery
      (>70%), except for thiophanate methyl (50%), whilst also yielding limits of
      detection (<0.03 mg kg(-1)) that are adequate for the determination of the
      studied fungicides in oranges.

PMID- 11330800
TI  - Determination of mercaptobenzimidazol and other thyreostat residues in thyroid
      tissue and meat using high-performance liquid chromatography-mass spectrometry.
AB  - This paper describes a method for extraction of tapazol, thiouracil,
      methylthiouracil, propylthiouracil and mercaptobenzimidazol (MBI) from thyroid
      tissue. The solid-phase extraction procedure is optimized to obtain the maximum
      results for the main thyreostats including MBI. Different combinations of sample
      application, column conditioning and wash steps were tested. The analytes were
      extracted from the matrix with methanol. After solid-phase extraction they were
      derivatised with 7-chloro-4-nitrobenzo-2-furazan. Determination is carried out
      using liquid chromatography-electrospray mass spectrometry. The identification of
      the analytes was performed according to the final revision of the EU criteria
      (93/256/EC decision). The detection capability was 20 microg kg(-1) for all
      mentioned thyreostats.

PMID- 11330802
TI  - Analysis of waterborne paints by gas chromatography-mass spectrometry with a
      temperature-programmable pyrolyzer.
AB  - Gas chromatography-mass spectrometry (GC-MS) with a temperature-programmable
      pyrolyzer was used for the analysis of waterborne paints. Evolved gas analysis
      (EGA) profiles of the waterborne paints were obtained by this temperature
      programmed pyrolysis directly coupled with MS via a deactivated metal capillary
      tube. The EGA profile suggested the optimal thermal desorption conditions for
      solvents and additives and the subsequent optimal pyrolysis temperature for the
      remaining polymeric material. Polymers were identified from pyrograms with the
      assistance of a new polymer library. The solvents were identified from the
      electron ionization mass spectra with the corresponding chemical ionization mass
      spectra. The additive was identified as zinc pyrithione by comparison with
      authentic standard. Zinc pyrithione cannot be analyzed by GC-MS as it is.
      However, the thermal decomposition products of zinc pyrithione could be detected.
      The information on the decomposition temperature and products was useful for the
      identification of the original compound.

PMID- 11330801
TI  - Simultaneous determination of arsenic species and chromium(VI) by high
      performance liquid chromatography-inductively coupled plasma-mass spectrometry.
AB  - The simultaneous determination of As(III), As(V), monomethylarsenic acid (MMA),
      dimethylarsinic acid (DMA) and Cr(VI) in fresh water has been carried out by
      coupling an anion-exchange column to an inductively coupled plasma-mass
      spectrometer. Optimisation of chromatographic conditions led to baseline
      separation of signals from the five species in approximately 9 min using gradient
      elution. Detection limits were 0.02-0.05 microg As l(-1) and 5.5 microg Cr l(-1).
      Repeatability was 2-3% for arsenic species and higher, i.e., 8%, for Cr(VI) due
      to the higher background for this species. Arsenic species and hexavalent
      chromium stability in surface water samples was evaluated, and storage conditions
      were set to 1 day at 4 degrees C in polyethylene flasks (without acidification)
      in order to avoid As(III)-As(V) conversions. The method was applied to the
      analysis of surface water.

PMID- 11330803
TI  - Chromatographic behavior of poly(styrene-divinybenzene) encapsulated packing
      material for capillary electrochromatography.
AB  - Poly(styrene-divinylbenzene) encapsulated silica (PS-DES) was synthesized and its
      characteristics as capillary electrochromatography stationary phase were studied.
      On capillary columns packed with this stationary phase, the effects of
      acetonitrile concentration as well as pH values on electroosmotic flow, and the
      effect of the latter on column efficiency were evaluated. Aromatic hydrocarbons,
      polar and basic medicinal compounds were successfully separated by using reversed
      phase elution. It was evident that selectivity based on pi-pi electronic
      interaction between solute and stationary phase molecules contributed to the
      separation. Peaks in the chromatograms obtained were generally symmetrical. At a
      pH of the mobile phase as high as 11.2, the stationary phase was still stable
      after more than 160 h of exposure.

PMID- 11330804
TI  - On-line sample concentration in micellar electrokinetic chromatography with
      cationic micelles in a coated capillary.
AB  - The electroosmotic flow was successfully suppressed even in the presence of
      cationic surfactants, when a polyacrylamide-coated capillary was employed. Two on
      line sample concentration techniques of sample stacking and sweeping were
      evaluated in micellar electrokinetic chromatography (MEKC) using the
      polyacrylamide-coated capillary. Cationic surfactants were used as
      pseudostationary phases in MEKC. At least 60-fold and about 600-fold increases in
      detection sensitivity were obtained in terms of peak heights by sample stacking
      and sweeping, respectively.

PMID- 11330805
TI  - Sample stacking with matrix removal for the determination of paraquat, diquat and
      difenzoquat in water by capillary electrophoresis.
AB  - Conditions for the simultaneous determination of paraquat, diquat and difenzoquat
      by capillary zone electrophoresis using a stacking technique in a chemically
      modified capillary have been established. To apply the stacking method with
      sample matrix removal for the analysis of cations, an anodic electroosmotic flow
      is mandatory. For quats, 50 mM acetic acid-ammonium acetate (pH 4.0) with 5%
      (v/v) methanol as electrophoretic buffer and the addition of 0.8 mM
      cetyltrimethylammonium bromide as wall capillary organic modifier was proposed.
      Field polarity reversal time was optimised for several sample matrices. Detection
      was carried out at 220 and 255 nm. Detection limits, based on a signal-to-noise
      ratio of 3:1, were lower than 15 microg l(-1) for standards in Milli-Q water and
      two to ten times higher for drinking water samples. Run-to-run and day-to-day
      reproducibility have been established. The method was successfully applied to the
      determination of the three herbicides in spiked drinking water.

PMID- 11330806
TI  - Direct determination of sinigrin in mustard seed without desulfatation by
      reversed-phase ion-pair liquid chromatography.
AB  - Reversed-phase ion-pair liquid chromatography has been investigated for directly
      analyzing sinigrin in mustard seed without desulfatation. After extraction by
      phosphate buffer (pH 7.0) from the grind-pastes of inactivated-myrosinase mustard
      seeds, sinigrin was first isolated through deproteinization and centrifugation,
      followed by filtration and injection into the chromatographic system. A reversed
      phase C18 column was used to separate the sinigrin with an eluent of acetonitrile
      (ACN)-water (20:80) containing 0.02 M tetrabutylammonium (TBA) as the counter ion
      at pH 7.0. Detection was carried out with an UV detector operated at 227 nm.
      Factors affecting the chromatographic separation and quantitative determination,
      such as concentrations of TBA and ACN, and pH, were studied. The linear dynamic
      range is larger than three orders of magnitude and the detection limit is 0.045
      mg/L. The RSD is around 3% and the recovery is 85% (3% RSD, n = 3).

PMID- 11330807
TI  - Isolation and structural characterization of polymyxin B components.
AB  - Polymyxin B is a peptide antibiotic complex present as sulphate. The components
      were separated preparatively on a poly(styrene-divinylbenzene) (PLRP-S), 1000 A,
      8 microm, 250 x 12.5 mm I.D. stationary phase maintained at 60 degrees C and
      using 215 nm detection. Elution was carried out with acetonitrile-sodium sulphate
      solution (0.7%, m/v; pH adjusted to 2.5 with trifluoroacetic acid)-water
      (18:50:32, v/v) at a flow-rate of 4.0 ml/min. Seven polymyxin B components were
      isolated and characterized using 1H and 13C NMR. The molecular masses were
      confirmed by mass spectrometry. The structures of two components were determined
      for the first time. Polymyxins B5 and B6 were identified as having the same
      composition as polymyxin B1 except that the fatty acid moiety was nonanoic acid
      and 3-hydroxy-6-methyloctanoic acid, respectively.

PMID- 11330808
TI  - Determination of the electron self-exchange rates of blue copper proteins by
      super-WEFT NMR spectroscopy.
AB  - An NMR approach for determining the electron self-exchange (ESE) rate constants
      in blue copper proteins is presented. The approach uses the paramagnetic
      relaxation enhancement of resonances in 1D 1H super-WEFT spectra of partly
      oxidized (paramagnetic) proteins. These spectra allow a more precise
      determination of the relevant paramagnetic linebroadenings than conventional 1D
      1H spectra and, thus, permit a more detailed investigation of the applicability
      of the linebroadenings for determining the electron exchange rates. The approach
      was used to estimate the ESE rate constant of plastocyanin from Anabaena
      variabilis. It was found that, although the rate constant can be determined
      accurately from a series of resonances, precise but erroneous constants are
      obtained from the resonances of the copper-bound residues, unless a narrow
      splitting of these resonances caused by the presence of two conformations is
      taken into account. As demonstrated here, this complication can be overcome by a
      correct analysis of the paramagnetic broadening of the combined double signals.
      Because of the high resolution and specific sensitivity of the approach it should
      be generally applicable to estimate electron transfer rates, k, if the
      paramagnetic relaxation enhancement R2p of the resonances can be determined, and
      the conditions k << R2p or delta omega(p) >> k >> R2p are fulfilled, delta
      omega(p) being the frequency separation between corresponding diamagnetic and
      paramagnetic sites.

PMID- 11330809
TI  - Anisotropic rotational diffusion in model-free analysis for a ternary DHFR
      complex.
AB  - Model-free analysis has been extensively used to extract information on motions
      in proteins over a wide range of timescales from NMR relaxation data. We present
      a detailed analysis of the effects of rotational anisotropy on the model-free
      analysis of a ternary complex for dihydrofolate reductase (DHFR). Our findings
      show that the small degree of anisotropy exhibited by DHFR
      (Dparallel/Dperpendicular = 1.18) introduces erroneous motional models, mostly
      exchange terms, to over 50% of the NH spins analyzed when isotropic tumbling is
      assumed. Moreover, there is a systematic change in S2, as large as 0.08 for some
      residues. The significant effects of anisotropic rotational diffusion on model
      free motional parameters are in marked contrast to previous studies and are
      accentuated by lowering of the effective correlation time using isotropic
      tumbling methods. This is caused by the preponderance of NH vectors aligned
      perpendicular to the principal diffusion tensor axis and is readily detected
      because of the high quality of the relaxation data. A novel procedure, COPED
      (COmparison of Predicted and Experimental Diffusion tensors) is presented for
      distinguishing genuine motions from the effects of anisotropy by comparing
      experimental relaxation data and data predicted from hydrodynamic analyses. The
      procedure shows excellent agreement with the slow motions detected from the
      axially symmetric model-free analysis and represents an independent procedure for
      determining rotational diffusion and slow motions that can confirm or refute
      established procedures that rely on relaxation data. Our findings show that
      neglect of even small degrees of rotational diffusion anisotropy can introduce
      significant errors in model-free analysis when the data is of high quality. These
      errors can hinder our understanding of the role of internal motions in protein
      function.

PMID- 11330810
TI  - Improved NMR spectra of a protein-DNA complex through rational mutagenesis and
      the application of a sensitivity optimized isotope-filtered NOESY experiment.
AB  - The NMR spectra of the complex between the DNA-binding domain of the Dead ringer
      protein (DRI-DBD, Gly262-Gly398) and its DNA binding site (DRI-DBD:DNA, 26 kDa)
      have been optimized by biochemical and spectroscopic means. First, we demonstrate
      the utility of a modified 2D [F1,F2] 13C-filtered NOESY experiment that employs a
      1J(HC) versus chemical shift optimized adiabatic 13C inversion pulse [Zwahlen, C.
      et al. (1997) J. Am. Chem. Soc., 119, 6711-6721]. The new sequence is shown to be
      more sensitive than previously published pulse schemes (up to 40% in favorable
      cases) and its utility is demonstrated using two protein-DNA complexes. Second,
      we demonstrate that the targeted replacement of an interfacial aromatic residue
      in the DRI-DBD:DNA complex substantially reduces line broadening within its NMR
      spectra. The spectral changes are dramatic, salvaging a protein-DNA complex that
      was originally ill suited for structural analysis by NMR. This biochemical
      approach is not a general method, but may prove useful in the spectral
      optimization of other protein complexes that suffer from interfacial line
      broadening caused by dynamic changes in proximal aromatic rings.

PMID- 11330811
TI  - Heteronuclear 2D-correlations in a uniformly [13C, 15N] labeled membrane-protein
      complex at ultra-high magnetic fields.
AB  - One- and two-dimensional solid-state NMR experiments on a uniformly labeled
      intrinsic membrane-protein complex at ultra-high magnetic fields are presented.
      Two-dimensional backbone and side-chain correlations for a [U-13C, 15N] labeled
      version of the LH2 light-harvesting complex indicate significant resolution at
      low temperatures and under Magic Angle Spinning. Tentative assignments of some of
      the observed correlations are presented and attributed to the alpha-helical
      segments of the protein, mostly found in the membrane interior.

PMID- 11330812
TI  - Measurement of one-bond 1H-13C, couplings in backbone-labelled proteins.
AB  - NMR dipole-dipole couplings between protein backbone nuclei (1H(alpha),
      13C(alpha), 15N, 1H(N), 13C') offer enormous scope for the rapid determination of
      protein global folds. Here, we show that measurement of one-bond splittings in
      the protein backbone is facilitated by use of protein that is selectively
      isotopically enriched only in the backbone atoms. In particular, 1H(alpha)
      13C(alpha) couplings can be measured simply and with high sensitivity by use of
      conventional heteronuclear single quantum correlation (HSQC) techniques.

PMID- 11330813
TI  - Improved sensitivity in indirect monitoring of chemical shifts of proton
      heteronuclear spin pairs (1H-13C and 1H-15N) in 3D and 4D NMR spectroscopy.
AB  - In three-dimensional and four-dimensional experiments on doubly labelled proteins
      not only heteronuclear (13C or 15N) but also proton (1H) frequencies are often
      indirectly monitored, rather than being directly observed. In this communication
      we show how in these experiments by overlaying 1H and heteronuclear evolutions
      one can obtain decreased apparent relaxation rates of 1H signals, yielding
      improved sensitivity. The new method applies to spin pairs like 1H-15N, as in
      amide groups, or 1H-13C, as in methine groups of alpha or aromatic systems.

PMID- 11330814
TI  - Selective 'unlabeling' of amino acids in fractionally 13C labeled proteins: an
      approach for stereospecific NMR assignments of CH3 groups in Val and Leu
      residues.
AB  - A novel methodology for stereospecific NMR assignments of methyl (CH3) groups of
      Val and Leu residues in fractionally 13C-labeled proteins is presented. The
      approach is based on selective 'unlabeling' of specific amino acids in proteins
      while fractionally 13C-labeling the rest. A 2D [13C-1H] HSQC spectrum recorded on
      such a sample is devoid of peaks belonging to the 'unlabeled' amino acid
      residues. Such spectral simplification aids in unambiguous stereospecific
      assignment of diastereotopic CH3 groups in Val and Leu residues in large
      proteins. This methodology has been demonstrated on a 15 kDa calcium binding
      protein from Entamoeba histolytica (Eh-CaBP).

PMID- 11330815
TI  - Sensitive 1H-31P correlations with 5' methylene protons of DNA via homonuclear
      double-quantum coherence.
AB  - A novel pulse sequence is presented for the correlation of 5' and 5'' protons in
      DNA with phosphorus. Double-quantum coherence between the methylene protons is
      used to generate 1H5'-31P and 1H5''-31P cross peaks in an HMQC-type experiment.
      The resolution for these cross peaks is significantly improved over that of
      conventional HSQC experiments, as cross peaks between 1H4' and 31P are largely
      suppressed and a 3D version of the experiment can be performed with little
      penalty in sensitivity. In addition, sensitivity is favoured by slower relaxation
      of the double-quantum coherence and a more favourable multiplet fine structure in
      the acquisition dimension.

PMID- 11330816
TI  - 1H, 15N and 13C assignments of a monomeric N-terminal deletion mutant of the Rous
      sarcoma virus protease.

PMID- 11330817
TI  - Assignment of the 1H, 15N, 13C resonances of the N-terminal domain of the human
      TFIIH P62 subunit.

PMID- 11330818
TI  - Backbone 1H, 15N and 13C resonance assignments of the NTPase subdomain of the
      hepatitis C virus NS3 RNA helicase.

PMID- 11330819
TI  - Resonance assignments for the N-terminal domain from human RNA-binding protein
      with multiple splicing (RBP-MS).

PMID- 11330820
TI  - Sequential assignment and secondary structure of the 14 kDa chemotactic protein
      CheY2 from Sinorhizobium meliloti.

PMID- 11330821
TI  - 1H, 13C, 15N resonance assignments and fold verification of a circular permuted
      variant of the potent HIV-inactivating protein cyanovirin-N.

PMID- 11330822
TI  - Complete sequence-specific 1H, 13C and 15N resonance assignments of the human
      PTK6 SH2 domain.

PMID- 11330823
TI  - An essential role of active site arginine residue in iodide binding and histidine
      residue in electron transfer for iodide oxidation by horseradish peroxidase.
AB  - The objective of the present study is to delineate the role of active site
      arginine and histidine residues of horseradish peroxidase (HRP) in controlling
      iodide oxidation using chemical modification technique. The arginine specific
      reagent, phenylglyoxal (PGO) irreversibly blocks iodide oxidation following
      pseudofirst order kinetics with second order rate constant of 25.12 min(-1) M(
      1). Radiolabelled PGO incorporation studies indicate an essential role of a
      single arginine residue in enzyme inactivation. The enzyme can be protected both
      by iodide and an aromatic donor such as guaiacol. Moreover, guaiacol-protected
      enzyme can oxidise iodide and iodide-protected enzyme can oxidise guaiacol
      suggesting the regulatory role of the same active site arginine residue in both
      iodide and guaiacol binding. The protection constant (Kp) for iodide and guaiacol
      are 500 and 10 microM respectively indicating higher affinity of guaiacol than
      iodide at this site. Donor binding studies indicate that guaiacol competitively
      inhibits iodide binding suggesting their interaction at the same binding site.
      Arginine-modified enzyme shows significant loss of iodide binding as shown by
      increased Kd value to 571 mM from the native enzyme (Kd = 150 mM). Although
      arginine-modified enzyme reacts with H2O2 to form compound II presumably at a
      slow rate, the latter is not reduced by iodide presumably due to low affinity
      binding. The role of the active site histidine residue in iodide oxidation was
      also studied after disubstitution reaction of the histidine imidazole nitrogens
      with diethylpyrocarbonate (DEPC), a histidine specific reagent. DEPC blocks
      iodide oxidation following pseudofirst order kinetics with second order rate
      constant of 0.66 min(-1) M(-1). Both the nitrogens (delta, epsilon) of histidine
      imidazole were modified as evidenced by the characteristic peak at 222 nm. The
      enzyme is not protected by iodide suggesting that imidazolium ion is not involved
      in iodide binding. Moreover, DEPC-modified enzyme binds iodide similar to the
      native enzyme. However, the modified enzyme does not form compound II but forms
      compound I only with higher concentration of H2O2 suggesting the catalytic role
      of this histidine in the formation and autoreduction of compound I.
      Interestingly, compound I thus formed is not reduced by iodide indicating block
      of electron transport from the donor to the compound I. We suggest that an active
      site arginine residue regulates iodide binding while the histidine residue
      controls the electron transfer to the heme ferryl group during oxidation.

PMID- 11330824
TI  - All-D-cecropin B: synthesis, conformation, lipopolysaccharide binding, and
      antibacterial activity.
AB  - Cecropin B (LCB) is a natural peptide with antibacterial and antifungal
      properties. The enantiomer of LCB, containing all-D amino acids (DCB), was
      synthesized to examine its antibacterial and binding properties. The conformation
      of DCB was compared to its enantiomer by circular dichroism. Both the L- and D
      peptides showed an identical induction of alpha-helical secondary structure.
      However, binding studies between Lipopolysaccharide (LPS) and DCB or LCB were
      studied with a dimethylmethylene blue spectrophotometric assay, showing the two
      enantiomeric peptides differed in their interaction with LPS. Antibacterial
      activity of DCB was determined against three Gram-negative bacteria, Pantoea
      agglomerans (ATCC 27996), Escherichia coli (ATCC 8739), and Pseudomonas
      aeruginosa (ATCC 17648), giving comparable results to LCB.

PMID- 11330825
TI  - The role of angiotensin II, endothelin-1 and transforming growth factor-beta as
      autocrine/paracrine mediators of stretch-induced cardiomyocyte hypertrophy.
AB  - Cardiac hypertrophy is a compensatory response of myocardial tissue upon
      increased mechanical load. Of the mechanical factors, stretch is rapidly followed
      by hypertrophic responses. We tried to elucidate the role of angiotensin II
      (AII), endothelin-1 (ET-1) and transforming growth factor-beta (TGF-beta) as
      autocrine/paracrine mediators of stretch-induced cardiomyocyte hypertrophy. We
      collected conditioned medium (CM) from stretched cardiomyocytes and from other
      stretched cardiac cells, such as cardiac fibroblasts, endothelial cells and
      vascular smooth muscle cells (VSMCs). These CMs were administered to stationary
      cardiomyocytes with or without an AII type 1 (AT1) receptor antagonist
      (losartan), an ET-1 type A (ET(A)) receptor antagonist (BQ610), or anti-TGF-beta
      antibodies. By measuring the mRNA levels of the proto-oncogene c-fos and the
      hypertrophy marker gene atrial natriuretic peptide (ANP), the molecular phenotype
      of the CM-treated stationary cardiomyocytes was characterized. Our results showed
      that c-fos and ANP expression in stationary cardiomyocytes was increased by All
      release from cardiomyocytes that had been stretched for 60 min. Stretched
      cardiomyocytes, cardiac fibroblasts and endothelial cells released ET-1 which led
      to increased c-fos and ANP expression in stationary cardiomyocytes. ET-1 released
      by stretched VSMCs, and TGF-beta released by stretched cardiac fibroblasts and
      endothelial cells, appeared to be paracrine mediators of ANP expression in
      stationary cardiomyocytes. These results indicate that AII, ET-1 and TGF-beta
      (released by cardiac and vascular cell types) act as autocrine/paracrine
      mediators of stretch-induced cardiomyocyte hypertrophy. Therefore, it is likely
      that in stretched myocardium the cardiomyocytes, cardiac fibroblasts, endothelial
      cells and VSMCs take part in intercellular interactions contributing to
      cardiomyocyte hypertrophy.

PMID- 11330826
TI  - Ionic and cofactor requirements for the activity of the apoptotic endonuclease
      DFF40/CAD.
AB  - The endonuclease DFF40/CAD mediates regulated DNA fragmentation and chromatin
      condensation in cells undergoing apoptosis. Here we report the enzyme's co-factor
      requirements, and demonstrate that the ionic changes that occur in apoptotic
      cells maximize DFF40/CAD activity. The nuclease requires Mg2+, exhibits a trace
      of activity in the presence of Mn2+, is not costimulated by Ca2+, is inhibited by
      Zn2+ or Cu2+, and has high activity over a rather broad pH range (7.0-8.5). The
      enzyme is thermally unstable, and is rapidly inactivated at 42 degrees C. Enzyme
      activity is markedly affected by ionic strength. At the optimal [K+] of 50-125
      mM, which is in the range of the cytoplasmic [K+] for cells undergoing apoptosis,
      the activity of DFF40/CAD for naked DNA cleavage is about 100-fold higher than at
      0 or 200 mM [K+]. Although these ranges of ionic strength do not affect DFF40
      homo-oligomer formation, at higher ionic strengths the enzyme introduces single
      stranded nicks into supercoiled DNA.

PMID- 11330827
TI  - Modifications in mitochondrial metabolism and ultrastructure and their
      relationship to tumour growth inhibition by gamma-linolenic acid.
AB  - Walker 256 tumour-bearing rats were fed pelleted chow containing low-gamma
      linolenic acid (GLA) (2.98%) or high-GLA (5.55%) during the twelve-day period
      after subcutaneous implantation of the tumour. The presence of n-6,
      polyunsaturated GLA in the diet caused a concentration-dependent decrease in
      tumour growth, reaching an almost 50% reduction in final tumour weight in the
      high-GLA group. The eicosatrienoic acid content of the whole tumour homogenate
      and of the Percoll-purified mitochondrial fraction was increased by the GLA-rich
      diets. Changes in the fatty acid composition of the cytoplasmic acyl CoA pool
      were also found, with increases in GLA content in both the low- and high-GLA
      groups. Additionally, increases in eicosatrienoic acid and arachidonic acid were
      found in the high-GLA group. Both the cytoplasmic acyl CoA content and the
      mitochondrial acyl CoA synthetase activity were increased by GLA in the diet and
      lipid peroxidation was also increased as determined by an increase in TBARS
      content. Changes in mitochondrial fatty acid composition were accompanied by a
      decrease in the mitochondrial membrane potential in the high-GLA group. Tumours
      from the control and GLA groups were examined by transmission electron
      microscopy. This revealed an increase in mitochondrial area and volume in the
      high-GLA group, in comparison with the control group, as well as a change in
      general cell ultrastructure, with many cells found in an apoptotic state or in a
      necrotic state, possibly secondary to apoptosis. The data presented show that the
      addition of GLA to the diet of Walker 256 tumour-bearing rats can greatly
      decrease the rate of development of the tumour burden. This may be, in part, due
      to the accumulation of poorly metabolised acyl CoA's within the tumour cell
      cytoplasm which, when coupled with altered mitochondrial composition, membrane
      potential and ultrastructure, may be a signal for cell death.

PMID- 11330828
TI  - Insulin regulates MAP kinase phosphatase-1 induction in Hirc B cells via
      activation of both extracellular signal-regulated kinase (ERK) and c-Jun-N
      terminal kinase (JNK).
AB  - Previously, we have reported that insulin induces the expression of the dual
      specificity tyrosine phosphatase Mitogen-activated protein (MAP) kinase
      phosphatase-1 (MKP-1) and that this may represent a negative feedback mechanism
      to regulate insulin-stimulated MAP kinase activity. In this work, the mechanism
      of regulation of MKP-1 expression by insulin was examined, particularly the role
      of the MAP kinase superfamily. Inhibition of the ERK pathway attenuated insulin
      stimulated MKP-1 mRNA expression. Expression of dominant negative molecules of
      the JNK pathway also abolished insulin-stimulated MKP-1 expression. However,
      inhibition of p38MAPK activity by SB202190 had no effect on insulin-stimulated
      MKP-1 induction. Simultaneous inhibition of the ERK and JNK pathways abolished
      the ability of insulin to stimulate MKP-1 expression, however, this combined
      inhibition was neither additive nor synergistic, suggesting these pathways
      converge to act on a common final effector. In conclusion, induction of MKP-1
      mRNA expression in Hirc B cells by insulin requires activation of both the ERK
      and JNK pathways, but not p38MAPK.

PMID- 11330829
TI  - Strain difference (WKY, SPRD) in the hepatic antioxidant status in rat and effect
      of hypertension (SHR, DOCA). Ex vivo and in vitro data.
AB  - We assessed the hepatic antioxidant status of spontaneously (SHR) and
      desoxicorticosterone acetate (DOCA)-induced hypertensive rats and that of
      respective normotensive Wistar Kyoto (WKY) and Sprague-Dawley (SPRD) rats. For
      this we evaluated, ex vivo in liver cytosols, reduced glutathione (GSH) content,
      glutathione-related enzyme (peroxidase, reductase and transferase) activities as
      well as the rate of lipid peroxidation in 9-11 week-old rats. The antioxidant
      status and the cytotoxicity of acetaminophen, a radical- and hydrogen peroxide
      mediated hepatotoxic compound, were also assessed in vitro in cultured
      hepatocytes isolated from hypertensive (SHR, DOCA) and normotensive control (WKY,
      SPRD) rats. Our results suggest that a difference exists in the hepatic
      antioxidant status between rat strains, with GSH levels being lower (-15%) and
      lipid peroxidation rate higher (+30%) in WKY compared to SPRD rats. In hepatocyte
      cultures from WKY rats, both GSH content and catalase activity were lower (-30
      and -70% respectively) compared to hepatocyte cultures from SPRD rats. This was
      associated with a 35% higher cytotoxicity of acetaminophen in cultured
      hepatocytes from WKY rats compared to that in hepatocytes from SPRD rats.
      Hypertension in DOCA rats (mmHg: 221+/-9 vs. 138+/-5 in control SPRD rats) was
      associated with decreases (about 30%) in both glutathione peroxidase (GSH-Px) and
      catalase activities, ex vivo in livers and in vitro in hepatocyte cultures.
      Hypertension in SHR (mmHg: 189+/-7 vs. 130+/-5 in control WKY rats) was also
      associated with decreases (about 50%) in GSH-Px activity, ex vivo in livers and
      in vitro in hepatocyte cultures but catalase activity was not modified. The IC50
      of acetaminophen was also lower in hepatocytes from hypertensive rats compared to
      respective controls, which could be related to the weakened antioxidant status in
      hepatocytes from hypertensive rats. Our data thus suggest that hepatocyte
      cultures are appropriated tools in which to assess hepatotoxicity and
      hepatoprotection in hypertension.

PMID- 11330831
TI  - Identification of beta subunit of the rhesus monkey chorionic gonadotropin
      (rmCG).
AB  - Chorionic gonadotropin (CG) is a placental derived hormone that plays a crucial
      role in successful implantation and establishment of early pregnancy in the
      primates. The rhesus monkey was chosen as a model to understand the feasibility
      of developing human DNA immuno-contraceptive. The coding region of rhesus monkey
      CG beta-subunit (rmCGbeta) was isolated by the TDRT-PCR method. The nucleotide
      sequence including the leader peptide was 499 nucleotide long and encoded 166
      amino acids. In comparing with the previous known primates CG beta-subunits, the
      rmCGbeta was the highest degree of homology with baboon CG beta-subunit at the
      deduced amino acid sequence (94%), 79.5% homology with human CG beta-subunit and
      70.4% homology with marmoset monkey CG beta-subunit. The eukaryotic expression
      vector pCMV4-rmCGbeta inserted full-coding cDNA sequence of rmCGbeta was
      constructed, and the expression of rmCG beta-subunit in HeLa cells transient
      expressing system in vitro and BALB/c mice in vivo was determined. The results
      demonstrated that the recombinant PCMV4-rmCGbeta eukaryotic expression vector
      could express rmCG beta-subunit in vitro and in vivo.

PMID- 11330830
TI  - Evaluation of antioxidant activity of epigallocatechin gallate in biphasic model
      systems in vitro.
AB  - The antioxidant activity of epigallocatechin gallate (EGCG) was studied in
      different in vitro model systems, which enabled evaluation of both chemical and
      physical factors involved in assessing the role of EGCG in oxidative reactions.
      EGCG suppressed the initiation rate and prolonged the lag phase duration of
      peroxyl radical-induced oxidation in a phospholipid liposome model to a greater
      extent (p < 0.01) compared to both Trolox and alpha-tocopherol. Effectiveness of
      these antioxidants to prolong the peroxyl radical-induced lag phase was inversely
      related to lipophilic character. EGCG also protected against both peroxyl radical
      and hydroxyl radical-induced supercoiled DNA nicking. The rate constant
      describing EGCG reaction against hydroxyl radical was 4.22+/-0.07 x 10(10) M(-1)
      x sec(-1), which was comparable to those of Trolox and alpha-tocopherol,
      respectively. EGCG exhibited a synergistic effect with alpha-tocopherol in
      scavenging 1,1-diphenyl-2-picylhydrazyl (DPPH) radical, thus displaying a direct
      free radical scavenging capacity. In vitro Cu2+-induced-human LDL oxidation was
      accelerated in the presence of EGCG and attributed to the conversion of Cu2+ to
      Cu+. We conclude that the particularly effective antioxidant properties of EGCG
      noted in both chemical and biological biphasic systems were related to a unique
      hydrophilic and lipophilic balance which enabled effective free radical
      scavenging. The same chemical-physical properties of EGCG also enabled prooxidant
      activity, only when in contact with unbound transition metal ions in a
      multiphasic system.

PMID- 11330833
TI  - Distribution of cells bearing B-cell alloantigen(s) in North Indian rheumatic
      fever/rheumatic heart disease patients.
AB  - Numerous investigators have developed monoclonal antibodies against B-cell
      alloantigen(s) of rheumatic fever. However, the developed monoclonals do not have
      the same significance in all the populations. We have developed a battery of
      monoclonals against B-cell alloantigens of North Indian rheumatic fever patients.
      In the present study, we have used these monoclonals to examine the frequency of
      rheumatic antigens in 30 patients with recurrence of rheumatic activity (RRA), 30
      of rheumatic heart disease (RHD) patients and 50 controls using alkaline
      phosphatase anti-alkaline phosphatase (APAAP) technique. These patients were
      examined at the time of registry and after three months follow up. RRA patients
      showed higher percentage of lymphocyte positive as compare to RHD and controls.
      Interestingly, on follow-up RRA patients showed significant decline in positive
      lymphocyte as compare to first visit whereas no such change was observed in RHD
      patients. There were 90-93% of RRA and RHD patients positive with these
      monoclonals. A significant age variation of rheumatic cells was also noticed in
      all groups of rheumatic patients. We conclude that monoclonals raised from the
      same ethnic population are highly specific and cost effective to use them to
      develop an easy field test system such as APAAP, to identify the individual at
      risk, to develop rheumatic fever. It is also suggested that the alloantigen
      marker may persist through out life and gets activated after recurrence of the
      disease.

PMID- 11330832
TI  - Effects of high-fat, low-cholesterol diets on hepatic lipid peroxidation and
      antioxidants in apolipoprotein E-deficient mice.
AB  - The present study describes the effects of several high-fat low-cholesterol
      antiatherogenic diets on the hepatic lipid peroxidation and hepatic antioxidant
      systems in apolipoprotein E-deficient mice. Eighty mice were distributed into
      five groups and fed with regular mouse chow or chow supplemented with coconut,
      palm, olive and sunflower seed oils. After ten weeks, they were sacrificed and
      the livers were removed so that lipid peroxidation and alpha-tocopherol
      concentrations, and superoxide dismutase, glutathione peroxidase and glutathione
      reductase activities could be measured. The size of the atherosclerotic lesions
      in the aortas was also measured. Results showed that the diets supplemented with
      olive oil, palm oil or sunflower seed oil significantly decreased the size of the
      lesion. However, there was an association between those mice that were on diets
      supplemented with palm or coconut oils and a significant increase in hepatic
      lipid peroxidation. This association was not found in animals fed with olive or
      sunflower seed oils, the diets with the highest content of vitamin E. The dietary
      content of vitamin E was significantly correlated (r = 0.98; p < 0.05) with the
      hepatic concentration of this compound. Our study suggests that the high content
      of vitamin E in olive oil or sunflower seed oil may protect from the undesirable
      hepatotoxic effects of high-fat diets in apo E-deficient mice and that this
      should be taken into account when these diets are used to prevent
      atherosclerosis.

PMID- 11330834
TI  - Differential effects of IH636 grape seed proanthocyanidin extract and a DNA
      repair modulator 4-aminobenzamide on liver microsomal cytochrome 4502E1-dependent
      aniline hydroxylation.
AB  - Previous studies from our laboratories have linked the protective abilities of
      IH636 grape seed proanthocyanidin extract (GSPE) with inactivation of anti
      apoptotic gene bcl-XL, and modification of several other critical molecular
      targets such as DNA-damage/DNA-repair, lipid peroxidation and intracellular Ca2+
      homeostasis. Especially, GSPE provided dramatic protection against acetaminophen
      (APAP)-induced hepatotoxicity, significantly increased bcl-XL expression in the
      liver, and antagonized both necrotic and apoptotic deaths of liver cells in vivo.
      However, it was not clear from this study whether anti-apoptogenic and anti
      necrotic effects of GSPE were: (i) due to its interference with endonuclease
      activity, (ii) due to its antioxidant effect, or, (iii) due to its ability to
      inhibit microsomal drug metabolizing enzyme(s), such as CYP-4502E1. Since CYP
      4502E1 primarily metabolizes acetaminophen in mice and rats, this study
      specifically focused on CYP-4502E1's catalytic activity in vitro. Overall this
      investigation compared the in vitro aniline hydroxylation patterns of: (i) in
      vivo GSPE-exposed and unexposed (control) mouse liver microsomes, (ii) induced
      (1% acetone in drinking water for 3 days) and uninduced rat liver microsomes in
      the presence and absence of GSPE in vitro, and (iii) control rat liver microsomes
      in the presence of an anti-APAP agent 4-aminobenzamide (4-AB) in vitro. For the
      in vivo assessment, male B6C3F1 mice were fed GSPE diet (ADI 100 mg/kg body wt)
      for 4 weeks, and liver microsomes were isolated from both control and GSPE-fed
      mice for aniline hydroxylation, a specific marker of CYP-4502E1 activity. Data
      show that hydroxylation was 40% less in microsomes from GSPE-exposed livers
      compared to control microsomes. Similarly, when rat liver microsomes were
      incubated with various concentrations of GSPE in vitro (100 and 250 microg/ml),
      aniline hydroxylation was inhibited to various degrees (uninduced: 40 and 60% and
      induced: 25 and 50%, respectively with 100 and 250 microg/ml). Influence of GSPE
      on hydroxylation patterns were compared with another hepatoprotective agent 4
      aminobenzamide (4-AB), a well-known modulator of nuclear enzyme poly(ADP-ribose)
      polymerase, and the data shows that 4-AB did not alter aniline hydroxylation at
      all. Collectively, these results may suggest that GSPE has the ability to inhibit
      CYP-4502E1, and this is an additional cytoprotective attribute, in conjunction
      with its novel antioxidant and/or antiendonucleolytic potential.

PMID- 11330835
TI  - Inhibitory effect of glycation on catalytic activity of alanine aminotransferase.
AB  - Non-enzymatic glycation is a common post-translational modification of tissue and
      plasma proteins which can impair their functions in living organisms. In this
      study, the authors have demonstrated for the first time an inhibitory effect of
      in vitro glycation on the catalytic activity of alanine aminotransferase (ALT, EC
      2.6.1.2), a pyridoxal phosphate enzyme with several lysine residues in the
      molecule. The porcine heart enzyme was incubated with 50 mmol/l D-fructose, D
      glucose, D,L-glyceraldehyde, or D-ribose in 0.1 mol/l phosphate buffer (pH 7.4)
      at 25 degrees C for up to 20 days. The strongest glycation effect was shown by
      D,L-glyceraldehyde, which caused complete enzyme inhibition within 6 days. After
      20 days of incubation, the ALT activity in samples with D-fructose and D-ribose
      was less than 7% of the initial enzyme activity. A statistically significant
      effect of D-glucose on the enzymatic activity of ALT was not found. Incubation of
      ALT with D-fructose, D,L-glyceraldehyde and D-ribose minimized its catalytic
      activity both in the glycated and non-glycated fractions of the samples. Markedly
      higher activity was found in the glycated fraction with glucose. The inhibitory
      effect of glycation of ALT with D-fructose and D-ribose was found to be more
      intensive in the presence of L-alanine and weaker in the presence of 2
      oxoglutarate. The findings suggest that glycation of the epsilon-amino group of
      Lys313 as a crucial part of the catalytic site of ALT may contribute to ALT
      inactivation in the presence of glycating sugars. Nevertheless, glycation of
      lysine residues outside the active center of ALT seems to be primary.

PMID- 11330836
TI  - Characterization of a Na+-Ca2+ exchanger NCX1 isoform in bovine fasciculata cells
      of adrenal gland.
AB  - The Na+-Ca2+ exchanger (NCX) is well known to regulate intracellular Ca2+
      concentration in many excitable cells. To date, three members of the NCX
      exchanger gene family have been identified: NCX1, NCX2 and NCX3. In zona
      fasciculata of the bovine adrenal gland, a Na+-Ca2+ exchanger has been recently
      found to display biochemical similarities with the NCX1 exchanger of renal
      basolateral cells. Although a Na+-Ca2+ exchanger has already been characterized
      in zona medulla of adrenal gland, such an exchanger has never been studied in the
      adrenal cortex. Thus, we have used a reverse transcriptase-polymerase chain
      reaction (RT-PCR) assay with specific NCX primers on fasciculata cell cultures.
      The sequencing of the amplified fragment revealed, for the first time, the
      presence of a NACA3 isoform of the NCX1 exchanger in the adrenal cortex, similar
      to the one found in adrenal chromaffin cells and in renal cortex. This isoform is
      92 and 94% identical in the portion compared with kidney Na+-Ca2+ exchanger NACA3
      of rat and pig, respectively.

PMID- 11330837
TI  - Association of ErbB2 Ser1113 phosphorylation with epidermal growth factor
      receptor co-expression and poor prognosis in human breast cancer.
AB  - The carboxyterminal domain of the epidermal growth factor receptor (EGFR)--a
      putative binding site for the ubiquitin ligase Cbl--is the site of serine
      phosphorylation events which are essential for ligand-dependent EGFR
      desensitization and degradation. Using a monoclonal antibody (aPS1113) which
      selectively recognizes the homologous phosphorylated domain in the ErbB2
      oncoprotein, we show here that wild-type ErbB2 becomes Ser1113-phosphorylated
      following treatment of 3T3 cells with growth factors or tyrosine phosphatase
      inhibitors. In EGFR-overexpressing A431 cells, ligand-inducible aPS1113
      immunoreactivity declines more rapidly than other detectable phosphorylation
      events and is followed by EGFR downregulation. Analysis of 65 ErbB2-expressing
      primary breast cancers reveals a highly significant relationship between Ser1113
      phosphorylation and EGFR overexpression (p < 0.0001) as well as an association
      with poor prognosis (p = 0.005). We submit that ErbB2 Ser1113 phosphorylation
      status represents a novel and informative biomarker of cancer cell biology and
      tumor behavior.

PMID- 11330838
TI  - Apoptosis, growth arrest and suppression of invasiveness by CRE-decoy
      oligonucleotide in ovarian cancer cells: protein kinase A downregulation and
      cytoplasmic export of CRE-binding proteins.
AB  - The CRE (cyclic AMP response element)-transcription factor complex plays a
      critical role in response to hormonal signals for cell proliferation,
      differentiation, and apoptosis. We have reported previously that the CRE
      transcription factor decoy oligonucleotide specifically slows tumor cell
      proliferation and inhibits CRE- and Ap-1-directed transcription in vivo (Park et
      al., 1999). We have investigated the effect of inhibiting CRE-directed
      transcription on ovarian cancer cell growth. Here, we report that CRE-decoy
      oligonucleotide treatment results in the inhibition of cell growth and a marked
      reduction in the expression of the regulatory and catalytic subunits of protein
      kinase A and the type I and type II protein kinase A holoenzymes. Growth
      inhibition was accompanied by changes in cell morphology, appearance of apoptotic
      nuclei, and DNA fragmentation. In addition, MMP-9 (matrix methalloproteinase-9)
      activity was markedly reduced in CRE-decoy treated cells. Indirect
      immunofluorescence revealed that CRE-decoy oligonucleotide treatment promoted
      export of the CRE-binding protein, CREB, from the nucleus to the cytoplasm, while
      importing the catalytic subunit of protein kinase A from the cytoplasm to the
      nucleus. The results indicate that the decoy oligonucleotide, by binding
      specifically to CRE-transcription factors, interferes with CRE-directed
      transcription in vivo. These results show a critical role for CRE-directed
      transcription in ovarian cancer cell growth. Thus, the CRE-decoy oligonucleotide
      may provide a powerful means to combat ovarian cancer.

PMID- 11330839
TI  - Effects of different carbohydrate sources on the growth of Tuber borchii Vittad.
      mycelium strains in pure culture.
AB  - The influence of carbohydrate utilisation on the growth of three strains of Tuber
      borchii Vittad. mycelium (1BO, 17BO and 10RA) in culture was assessed using
      culture media containing glucose (control), mannose or mannitol. Mannose was the
      best substrate for growth of the strains and this was particularly evident for
      strain 17BO. Mannitol instead was metabolized only by 10RA and 1BO. In order to
      explain the different growth trends, analyses of enzyme levels, kinetic
      parameters, protein patterns and the morphology of the three strains were carried
      out. Our results show that these strains of T. borchii mycelium were affected by
      the substrates used in the media. The aim of the present work was to optimise the
      in vitro production of T. borchii mycelium for use in experiments which require
      the fungus in precise and reproducible conditions, such as mycorrhizal synthesis
      or protein and nucleic acid extractions.

PMID- 11330840
TI  - Chemical modification and structural analysis of the progesterone membrane
      binding protein from porcine liver membranes.
AB  - In addition to the classical genomic steroid actions on modulation of
      transcription and protein synthesis, rapid, nongenomic effects have been
      described for various steroids. These effects on cellular signaling and function
      are supposed to be transmitted by membrane binding sites unrelated to the
      classical intracellular receptors. Recently, a high affinity progesterone
      membrane binding protein (mPR) has been characterized in porcine liver membranes.
      In the present study, amino acid residues that are essential for progesterone
      binding to porcine liver microsomal mPR have been identified by the use of
      protein modifying reagents. Among all reagents tested, agents with specificity
      for carboxyl groups, methionine and tryptophan such as N,N'
      dicyclohexylcarbodiimide, chloramine T and N-bromosuccinimide induced a reduction
      in [3H]progesterone binding. To evaluate the presence of essential disulfide
      bridges, porcine liver microsomes were incubated with the disulfide reducing
      agent dithiothreitol (DTT) and [3H]progesterone binding was measured. This
      treatment also resulted in a reduction of binding activity with an IC50 of 20 mM
      for DTT. Western-blotting analysis in the presence or absence of the reducing
      agent suggested that mPR--in its binding state--consists of at least two
      identical subunits with an apparent molecular mass of 28 kDa which are linked by
      a disulfide bridge. In conclusion, in the present study evidence for an
      involvement of carboxyl-, tryptophan- and methionine residues in [3H]progesterone
      binding to porcine liver microsomes is given. In addition, it is shown that mPR
      can form disulfide-linked homodimers.

PMID- 11330841
TI  - Participation of carnitine palmitoyltransferase in the synthesis of
      dipalmitoylphosphatidylcholine in rat alveolar type II cells.
AB  - We have investigated the role of carnitine palmitoyltransferase (EC 2.3.1.21) in
      pulmonar type II pneumocyte, a lung cell responsible for the synthesis of surface
      active lipids. Adult type II pneumocytes were isolated from rat lung and purified
      by differential adherence. When these lung cells were incubated with radioactive
      palmitate, the percentage of radioactivity recovered into
      dipalmitoylphosphatidylcholine (DPPC), a major surface active lipid, was almost
      60% with respect to total phosphatidylcholine (PC) molecular species. Cellular
      lysates from type II pneumocytes contained detectable amount of carnitine
      palmitoyltransferase (CPT) activity (1 nmol/min/mg). Most of the CPT activity
      found in these cells could be inhibited by incubating them for 60 min with 5
      microM tetradecylglycidic acid (TDGA), a specific and irreversible CPT inhibitor
      of the malonyl-CoA sensitive CPT isoform (CPT I). TDGA treatment of adult type II
      pneumocytes caused a significant reduction in the incorporation of radioactive
      palmitate into PC, though this effect did not seem to be specific for DPPC. TDGA
      affected the incorporation of radioactive palmitate at the sn2 rather than the
      sn1 position of the glycerol backbone of PC. The incorporation of radioactive
      palmitate into DPPC was also observed when these lung cells were incubated with
      palmitate-labeled palmitoyl-L-carnitine. Our data suggest that type II pneumocyte
      CPT may play an important role in remodelling PC fatty acid composition and hence
      DPPC synthesis.

PMID- 11330842
TI  - Melatonin prevents delta-aminolevulinic acid-induced oxidative DNA damage in the
      presence of Fe2+.
AB  - Delta-aminolevulinic acid (ALA), a heme precursor which accumulates during lead
      poisoning and acute intermittent porphyria, is reported to cause liver cancer.
      The carcinogenic mechanisms of ALA may relate to its ability to generate free
      radicals through metal-catalyzed oxidation which cause oxidative DNA damage. The
      aim of this study was to compare the efficacy of melatonin, trolox (vitamin E)
      and mannitol in altering DNA damage induced by ALA. Herein, we found, in the
      presence of Fe2+, that ALA-induced formation of 8-hydroxydeoxyguanosine in calf
      thymus DNA was dose and time-dependent. Melatonin, mannitol and trolox, all of
      which are free radical scavengers, inhibited the formation of 8
      hydroxydeoxyguanosine in a concentration-dependent manner. The concentration of
      each (melatonin, mannitol and trolox) required to reduce DNA damage by 50%, i.e.,
      the IC50, was 0.52, 0.84 and 0.90 mM, respectively.

PMID- 11330843
TI  - Effect of vanadium on insulin and leptin in Zucker diabetic fatty rats.
AB  - Vanadium exhibits a variety of insulin-mimetic actions in vitro and in vivo. The
      mechanism(s) of the effect of vanadium on leptin in Zucker diabetic fatty (ZDF)
      rats, a model of Type 2 diabetes, is unclear. Since insulin is a stimulator of
      leptin production and secretion and vanadium is an insulin-mimetic or insulin
      enhancing agent, we studied how vanadium affected plasma leptin levels in vivo
      and the relationship between plasma insulin, leptin and body fat in ZDF rats.
      Zucker lean and ZDF rats at 9-week old were chronically treated with
      bis(ethylmaltolato)oxovanadium(IV) (BEOV), an organic vanadium compound, by oral
      gavage daily for 3 weeks. At termination, the total body fat was weighed and
      blood was collected for insulin, leptin and glucose assay. BEOV treatment (0.1
      mmol/kg/day) significantly decreased plasma glucose levels in ZDF rats and did
      not change food intake and body fat content either in lean or ZDF rats. Following
      3-week treatment, plasma insulin and leptin levels in BEOV treated ZDF rats were
      significantly higher, 1.5 and 0.5 fold than untreated rats, respectively. The
      correlation coefficients in ZDF rats showed that plasma leptin levels were
      correlated to plasma insulin levels, but not to body fat. These data indicate
      that plasma leptin levels parallel plasma insulin levels, and the effects of
      vanadium on leptin appear to be mediated by insulin in ZDF rats.

PMID- 11330845
TI  - Paediatric rehabilitation: improving recovery and outcome in childhood disorders.

PMID- 11330844
TI  - Dietary vitamin C supplementation lowers blood pressure in spontaneously
      hypertensive rats.
AB  - In spontaneously hypertensive rats (SHRs) excess endogenous aldehydes bind
      sulfhydryl groups of membrane proteins, altering membrane Ca2+ channels and
      increasing cytosolic free calcium and blood pressure. The thiol compound, N
      acetyl cysteine, normalizes elevated blood pressure in SHRs by binding excess
      endogenous aldehydes. Vitamin C can increase tissue cysteine and glutathione
      levels. The aim of the present study was to investigate whether a dietary
      supplementation of vitamin C can lower tissue aldehydes and blood pressure and
      normalize associated biochemical and histopathological changes in SHRs. Starting
      at 12 weeks of age, animals were divided into 3 groups of 6 animals each. Animals
      in the WKY-control group and SHR-control group were given a normal diet and the
      SHR-vitamin C group a diet supplemented with vitamin C (1000 mg/kg feed) for the
      next 9 weeks. After nine weeks, systolic blood pressure, platelet [Ca2+]i, plasma
      insulin and liver, kidney and aortic aldehyde conjugates were significantly
      higher in SHR controls as compared to WKY controls and the SHR-vitamin C group.
      SHR-controls also showed smooth muscle cell hyperplasia in the small arteries and
      arterioles of the kidneys. Dietary vitamin C supplementation in SHRs lowered the
      systolic blood pressure, tissue aldehyde conjugates and attenuated adverse renal
      vascular changes.

PMID- 11330846
TI  - The evaluation of reaction time on mentally retarded children.
AB  - This study was designed to compare the parameters of reaction time on mentally
      retarded and healthy children and also to find out the effect of sport on
      reaction time. The study consisted of 20 non-retarded (group I), 20 non-sporting
      trainable mentally retarded (group II), and 20 sporting trainable mentally
      retarded (group III). The avarage age of subjects were determined as 15.35 +/-
      0.21 years in group I, 15.00 +/- 0.22 years in group II, and 15.15 +/- 0.21 years
      in group III. The audiovisual reaction time of both non-retarded and retarded
      children were measured. It was found that reaction time is lower in trainable
      mentally retarded children (p < 0.05). It can be concluded that sport is a valid
      and effective means of training which affects the reaction time positively.

PMID- 11330847
TI  - The quality of life of ventilator-assisted children.
AB  - Although an increasing number of ventilator-assisted children are being cared for
      in the home, few studies in the literature evaluate the resulting quality of life
      from multiple informant perspectives. A questionnaire was used to gather data on
      38 ventilator-assisted children from the children themselves and their caregivers
      about activities of daily living, measures of independence, and psychological
      state. The majority (79.4%) of ventilator-assisted children were perceived as
      either satisfied or very satisfied with how they spent their time, and most
      (77.1%) were rated as having an excellent or good emotional adjustment to the
      need for mechanical ventilation. Children older than 12 years were reported to be
      significantly less satisfied with their daily activities than the younger
      children, but greater activity levels correlated with greater levels of total
      satisfaction. A higher total satisfaction did not correlate with the age at onset
      of assisted ventilation, or the amount of time spent in other activities.
      Adolescents and primary caregivers had similar responses to most activity and
      independence parameters on the survey. There were no significant differences in
      parents' perceptions of the adolescents' emotional status as compared to the
      adolescents' self- assessment of their emotional status in any parameter.

PMID- 11330849
TI  - Complementary/alternative medicine in chronic paediatric diseases--prevalence and
      parental psychological factors.

PMID- 11330848
TI  - The role of botulinum toxin in the neuro-rehabilitation of young patients with
      brachial plexus birth palsy.
AB  - PURPOSE: To favour the active movements of the shoulder abductor/external
      rotator, elbow extensor and supinator muscles, through the partial inhibition of
      the uninvolved antagonistic muscles, in the Brachial Plexus birth Palsy (BPP).
      METHODS: The type A Botulinum Neuro Toxin (BNT-Dysport, Ipsen) was injected in 50
      outpatients (mean age: 4.7 +/- 3.4 years) with BPP according to the criteria:
      early and current neuro-rehabilitation (Reflex Locomotion-RL), age <14 years, no
      cognitive impairment. Repeat injections (1.9 +/- 0.8) were performed in 30
      patients. RESULTS: The range of active movements increased at the maximal benefit
      phase, compared to the baseline values (p < 0.05-0.01). The gain of shoulder's
      abduction was directly related to the youngest age (r = 0.6). An expanded
      compliance of the injected muscles and a faster response to the RL, in respect to
      that experienced in the pre-BNT sessions, was detected. The Global Clinical
      Rating Scale disclosed the temporal profile of the clinical outcome, with step
      like increases of the function in 70% of the patients, and a 'plateau' trait in
      the remaining ones (+29.8 +/- 10.5%). The video-taped recordings showed an
      improvement in the global movements. CONCLUSIONS: The employment of BNT in the
      management of young patients with BPP has beneficial effects in the integration
      of the bodily scheme.

PMID- 11330850
TI  - Treatment of neuromuscular and musculoskeletal problems in cerebral palsy.
AB  - Cerebral palsy typically involves a variety of neuromuscular and musculoskeletal
      problems. These problems include spasticity, dystonia, contractures, abnormal
      bone growth, poor balance, and loss of selective motor control. These problems
      can interfere with function and treating them can improve function. The
      treatments include physical and occupational therapy, bracing, oral medications,
      neurolytic blocks, neurosurgical procedures, orthopaedic surgery and others.
      Using a multidisciplinary treatment team with a good understanding of cerebral
      palsy, the best treatment options can be determined and functional outcomes
      maximized.

PMID- 11330851
TI  - Effects of a parent-child communications intervention on young adolescents' risk
      for early onset of sexual intercourse.
AB  - CONTEXT: The quality of parent-child communications about sex and sexuality
      appears to be a strong determinant of adolescents' sexual behavior. Evaluations
      of interventions aimed at improving such communications can help identify
      strategies for preventing early onset of sexual behavior. METHODS: A school-based
      abstinence-only curriculum was implemented among 351 middle school students, who
      were randomly assigned to receive either the classroom instruction alone or the
      classroom instruction enhanced by five homework assignments designed to be
      completed by the students and their parents. An experimental design involving
      pretest and posttest surveys was used to assess the relative efficacy of the
      curriculum delivered with and without the parent-child homework assignments.
      RESULTS: In analyses of covariance controlling for baseline scores, immediately
      after the intervention, adolescents who received the enhanced curriculum reported
      greater self-efficacy for refusing high-risk behaviors than did those who
      received the classroom instruction only (mean scores, 16.8 vs. 15.8). They also
      reported less intention to have sex before finishing high school (0.4 vs. 0.5),
      and more frequent parent-child communications about prevention (1.6 vs. 1.0) and
      sexual consequences (1.6 vs. 1.1). In all significant comparisons, the direction
      of the findings favored adolescents who received the enhanced curriculum. Dose
      response relationships supported the findings. CONCLUSIONS: Parent-child homework
      assignments designed to reinforce and support school-based prevention curricula
      can have an immediate impact on several key determinants of sexual behavior among
      middle school adolescents.

PMID- 11330852
TI  - Manifestations of poverty and birthrates among young teenagers in California zip
      code areas.
AB  - CONTEXT: Given that many communities are implementing community-wide initiatives
      to reduce teenage pregnancy or childbearing, it is important to understand the
      effects of a community's characteristics on adolescent birthrates. METHODOLOGY:
      Data from the 1990 census and from California birth certificates were obtained
      for zip codes in California. Regression analyses were conducted on data from zip
      code areas with at least 200 females aged 15-17 between 1991 and 1996, to predict
      the effects of race and ethnicity marital status, education, employment, income
      and poverty, and housing on birthrates among young teenagers. RESULTS: In
      bivariate analyses, the proportion of families living below poverty level within
      a zip code was highly related to the birthrate among young teenagers in that zip
      code (r=.80, p<.001). In multivariate analyses, which controlled for some of the
      correlates of family poverty level, the proportion of families living below
      poverty level remained by far the most important predictor of the birthrate among
      young teenagers (b=1.54), followed by the proportion of adults aged 25 or older
      who have a college education (b=-0.80). Race and ethnicity were only weakly
      related to birthrate. In all three racial and ethnic groups, poverty and
      education were significantly related to birthrate, but the effect of college
      education was greater among Hispanics (b=-2.98) than among either non-Hispanic
      whites (b=-0.53) or blacks (b=-1.12). Male employment and unemployment and female
      unemployment were highly related to the birthrate among young teenagers in some
      racial or ethnic groups, but not in others. CONCLUSIONS: Multiple manifestations
      of poverty, including poverty itself, low levels of education and employment, and
      high levels of unemployment, may have a large impact upon birthrates among young
      teenagers. Addressing some of these issues could substantially reduce
      childbearing among young adolescents.

PMID- 11330853
TI  - Teenage childbearing and long-term socioeconomic consequences: a case study in
      Sweden.
AB  - CONTEXT: Whether long-term socioeconomic problems experienced by many teenage
      mothers are a reflection of preexisting disadvantage or are consequences of
      teenage motherhood per se remains unclear. METHODS: National data on all women
      born in Sweden from 1941 to 1970 who were younger than age 30 when they first
      gave birth (N=888,044) were analyzed. The outcome measures, assessed during
      adulthood, were employment status, socioeconomic status, educational attainment,
      single motherhood, family size, receipt of disability pension and dependence on
      welfare. Multiple logistic regression techniques were used to adjust for maternal
      birth cohort and for socioeconomic background of the woman's family. RESULTS:
      Compared with Swedish women who first gave birth at ages 20-24, those who were
      teenage mothers had significantly increased odds of each unfavorable
      socioeconomic outcome in later life, even after the data were adjusted for family
      socioeconomic situation and maternal birth cohort. For example, teenage
      motherhood was positively associated with low educational attainment (odds ratios
      of 1.7-1.9, depending on the specific age during adolescence when the woman gave
      birth), with single living arrangements (odds ratios, 1.5-2.3), with high parity
      (odds ratios, 2.6-6.0), with collecting a disability pension (odds ratios, 1.6
      1.9) and with welfare dependency (odds ratios, 1.9-2.6). These trends were
      usually linear, with the highest odds ratios corresponding to women who had had
      their first child at the youngest ages. CONCLUSIONS: A longitudinal analysis of
      record-linkage data from Sweden supports the view that childbearing during
      adolescence poses a risk for socioeconomic disadvantage in later life--even for
      adolescents from relatively comfortable backgrounds and for those who studied
      beyond elementary school.

PMID- 11330854
TI  - Risks among youths who have multiple sisters who were adolescent parents.
AB  - CONTEXT: Past research has revealed that having a sister who gave birth as a
      teenager is associated with increases in young people's likelihood of engaging in
      risky sexual behavior. To date, however, no study has determined if having
      several sisters who were adolescent mothers further raises youths' chances of
      engaging in risky activities. METHODS: Data were collected from 1,510
      predominantly Hispanic and black 11-17-year-olds in a California program for
      youths who have at least one pregnant or parenting sister. Correlational
      analyses, analyses of variance and regression analyses were conducted to assess
      the effects of having multiple teenage parenting sisters on a variety of outcomes
      that are known risk factors for teenage pregnancy RESULTS: Twenty-four percent of
      participants had two or more sisters who had given birth as teenagers. The
      likelihood of having multiple adolescent parenting sisters was greatest in large
      families, but was unrelated to youths' other background characteristics. In
      analyses controlling for background factors, females with many parenting sisters
      had increased levels of behavioral problems (school problems, drug or alcohol
      use, and delinquent behavior) and an elevated likelihood of being sexually
      experienced. Having lived with two or more parenting sisters (as opposed to
      having lived with only one) was related to more permissive sexual and
      childbearing attitudes among young women and to earlier first intercourse among
      young men. Males with a sister who gave birth at a young age had elevated levels
      of delinquent behavior and promiscuous sexual behavior. CONCLUSIONS: As the
      number of teenage parenting sisters rises, youths'--particularly females'--risk
      of pregnancy involvement increases beyond the level associated with having only
      one teenage parenting sister. Screening for the number, living situation and age
      at first birth of parenting sisters is likely to be useful for programs seeking
      to identify youths at high risk of an early pregnancy.

PMID- 11330855
TI  - Reproductive health services for adolescents under the State Children's Health
      Insurance Program.
AB  - CONTEXT: The federal government enacted the State Children's Health Insurance
      Program (CHIP) in 1997 to provide insurance coverage to uninsured, low-income
      children up to age 19. Individual states' decisions when designing their CHIP
      efforts will in large part determine the extent to which the program will help
      the nation's nearly three million low-income uninsured adolescents get needed
      reproductive health services. METHODS: CHIP administrators in all states and the
      District of Columbia were sent a survey concerning reproductive health services
      for adolescents aged 13-18 provided under their state's CHIP effort. The
      questionnaire asked about services covered, information provided to adolescents,
      confidentiality, outreach and enrollment activities, managed care and performance
      measures. RESULTS: Of the 46 respondents to the survey, 29 states and the
      District of Columbia included a Medicaid component to their CHIP effort, and 28
      states included a state-designed component. Overall, states provided relatively
      comprehensive coverage of reproductive health services, with all 58 CHIP programs
      covering routine gynecologic care, screening for sexually transmitted diseases
      and pregnancy testing. Fifty-four covered the full range of the most commonly
      used prescription contraceptive methods, although only 43 covered emergency
      contraception. Twenty of 58 CHIP programs required that adolescents be provided
      with information about coverage for the full range of reproductive health
      services, and 18 required that information be provided about accessing care.
      Seventeen programs reported guarantees of confidentiality before and after
      receipt of reproductive health care. In 26 programs, enrollees in managed care
      were guaranteed access to contraceptive services through out-of-network
      providers. Twenty-six states and the District of Columbia reported targeting
      outreach activities specifically to adolescents, and 41 states and the District
      of Columbia stated that they provide outreach materials at middle schools, high
      schools and community-based organizations serving teenagers. CONCLUSIONS: Despite
      their nearly comprehensive coverage of reproductive health services, programs
      were inconsistent in guaranteeing the information, confidentiality and
      flexibility in choosing providers that is critical to adolescents' ability to
      access care. In addition, many states failed to creatively use strategies to
      target uninsured adolescents for enrollment, although new initiatives are under
      way to correct this problem.

PMID- 11330856
TI  - How available is abortion training?

PMID- 11330857
TI  - Xwig1, a novel putative endoplasmic reticulum protein expressed during epithelial
      morphogenesis and in response to embryonic wounding.
AB  - In a subtractive differential screening, we identified a novel gene with
      interesting characteristics, termed Xenopus wounding induced gene 1 (Xwig1).
      Xwig1 encodes a novel protein of 912 amino acids containing 13 putative
      transmembrane segments and an evolutionarily conserved carboxy-terminal domain.
      Protein localization studies revealed that Xwig1 is anchored in cytoplasmic
      structures, presumably the endoplasmic reticulum. Expression is largely confined
      to epithelial cells in regions that undergo morphogenetic processes, such as
      blastopore closure, hindgut closure, dorsal closure and optic vesicle
      invagination. Interestingly, Xwig1 transcription is activated in response to
      embryonic epidermal wounding. The wounding-induced transcription occurs
      downstream of the transient phosphorylation of extracellular signal-regulated
      protein kinases and is in part mediated by Elk-1, but independent of dissection
      induced FGF signalling. Thus, Xwig1 provides a molecular link between epithelial
      morphogenesis and wound healing.

PMID- 11330858
TI  - Two-step induction of primitive erythrocytes in Xenopus laevis embryos: signals
      from the vegetal endoderm and the overlying ectoderm.
AB  - Primitive blood cells differentiate from the ventral mesoderm blood islands in
      Xenopus embryos. In order to determine the tissue interactions that propagate
      blood formation in early embryogenesis, we used embryos that had the ventral
      cytoplasm removed. These embryos gastrulated normally, formed a mesodermal layer
      and lacked axial structures, but displayed a marked enhancement of alpha-globin
      expression. Early ventral markers, such as msx-1, vent-1 and vent-2 were highly
      expressed at the gastrula stage, while a dorsal marker, goosecoid, was
      diminished. Several lines of experimental evidence demonstrate the critical role
      of animal pole-derived ectoderm in blood cell formation: 1) Mesoderm derived from
      dorsal blastomeres injected with beta-galactosidase mRNA (as a lineage tracer)
      expressed alpha-globin when interfaced with an animal pole-derived ectodermal
      layer; 2) Embryos in which the animal pole tissue had been removed by dissection
      at the blastula stage failed to express alpha-globin; 3) Exogastrulated embryos
      that lacked an interaction between the mesodermal and ectodermal layers failed to
      form blood cells, while muscle cells were observed in these embryos. Using
      dominant-negative forms of the BMP-4 and ALK-4 receptors, we showed that activin
      and BMP-4 signaling is necessary for blood cell differentiation in ventral
      marginal zone explants, while FGF signaling is not essential. In ventralized
      embryos, inactivation of the BMP-4 signal within a localized area of the ectoderm
      led to suppression of globin expression in the adjacent mesoderm layer, but
      inactivation of the activin signal did not have this effect. These observations
      suggest that mesodermal cells, derived from a default pathway that is induced by
      the activin signal, need an additional BMP-4-dependent factor from the overlying
      ectoderm for further differentiation into a blood cell lineage.

PMID- 11330859
TI  - R-twist gene expression during rat palatogenesis.
AB  - Palatal clefting is often associated with premature fusion of cranial sutures in
      human craniosynostosis syndromes, many of which are characterised by mutations
      affecting the fibroblast growth factor receptor (FGFR) gene family. In palatal
      fusion, epithelio-mesenchymal transition (EMT) contributes to the dispersion of
      the midline epithelial seam. EMT has also been observed in neoplastic epithelial
      cells in relation to the acquisition of malignant characteristics where
      morphological changes are accompanied by rapid switching in the expression of
      fgfr2 from the epithelial type (kgfr) to the mesenchymal type (bek). The twist
      gene codes for a basic helix-loop-helix transcription factor putatively involved
      in regulation of transcription of fgfr2. Mutations in the TWIST gene have been
      described as being responsible for the Saethre-Chotzen syndrome, an autosomal
      dominant craniosynostosis associated with cleft palate as well as other
      disturbances of the facial skeleton. In this study we have analysed the
      distribution of twist transcripts during rat palatogenesis in vivo from 14.5 to
      17.5 days post coitum by in situ hybridisation with digoxygenin-labelled ssDNA
      probes. twist transcripts were found to be concentrated in mesenchymal cells
      beneath the epithelium at the tip of the palatal shelves immediately prior to,
      and during fusion as well as in a localised epithelial area at the tip of the
      shelves prior to fusion, thereby implicating twist gene expression in the process
      of palatogenesis. This pattern of expression illuminates the disturbances of
      maxillary growth that occur in human craniosynostotic syndromes.

PMID- 11330860
TI  - Cell cycle phase, cellular Ca2+ and development in Dictyostelium discoideum.
AB  - In Dictyostelium discoideum, the initial differentiation of cells is regulated by
      the phase of the cell cycle at starvation. Cells in S and early G2 (or with a low
      DNA content) have relatively high levels of cellular Ca2+ and display a prestalk
      tendency after starvation, whereas cells in mid to late G2 (or with a high DNA
      content) have relatively low levels of Ca2+ and display a prespore tendency. We
      found that there is a correlation between cytosolic Ca2+ and cell cycle phase,
      with high Ca2+ levels being restricted to cells in the S and early G2 phases. As
      expected on the basis of this correlation, cell cycle inhibitors influence the
      proportions of amoebae containing high or low Ca2+. However, it has been reported
      that in the rtoA mutant, which upon differentiation gives rise to many more stalk
      cells than spores (compared to the wild type), initial cell-type choice is
      independent of cell cycle phase at starvation. In contrast to the wild type, a
      disproportionately large fraction of rtoA amoebae fall into the high Ca2+ class,
      possibly due to an altered ability of this mutant to transport Ca2+.

PMID- 11330861
TI  - Developmental expression of the POU transcription factor qBrn-2 during somitic
      myogenesis in quail.
AB  - We prepared a specific antiserum to the qBrn-2 protein and examined the
      developmental distribution of this protein during quail somitic myogenesis. In
      contrast to its mammalian homolog N-Oct-3, qBrn-2 exhibited an impressive spatio
      temporal profile in somitic myogenesis, in addition to the orthodox expression
      observed in the developing neural tube. In somites, qBrn-2 was expressed in the
      outer epithelial cells, but not in the core cells. During the somite
      differentiation, qBrn-2 expression was enhanced and restricted to myotome. The
      location of qBrn-2 expression seemed to overlap with that of myf5 and myoD in
      myotome. However, in cells that just began to express myf5 or myoD, qBrn-2
      expression was not obvious. As embryonic development proceeded, qBrn-2 positive
      cells in myotome migrated dorsally and ventrally, and qBrn-2 expression was still
      observed at dorsal and ventral muscle masses in the forelimb. On the basis of our
      observations, it seems that qBrn-2 may play important roles in the determination,
      differentiation and migration of muscle precursor cells, in addition to its known
      roles in neurogenesis.

PMID- 11330862
TI  - Lithium influences differentiation and tissue-specific gene expression of mouse
      embryonic stem (ES) cells in vitro.
AB  - The effects of lithium chloride (LiCl) on differentiation of mouse embryonic stem
      (ES) cells were investigated in order to evaluate the ES cell test (EST) used in
      a European Union validation study for screening of embryotoxic agents in vitro.
      We show that LiCl inhibited concentration-dependently the differentiation of ES
      cells into cardiac and myogenic cells. Whereas the inhibition of cardiac
      differentiation by high concentrations of LiCl was obvious at day 5 + 5,
      decreased skeletal muscle cell differentiation was observed only at day 5 + 8.
      Semi-quantitative RT-PCR analyses revealed significantly lower levels of mRNA
      encoding cardiac-specific alpha-myosin heavy chain and skeletal muscle-specific
      myoD. By morphological investigation, an influence of lithium on neuronal
      differentiation was not evident. However, mRNA levels of genes encoding
      synaptophysin and the 160 kDa neurofilament protein were increased by high LiCl
      concentrations, whereas mRNA levels of mash-1 and Engrailed-1 were decreased,
      suggesting a specific influence of lithium on neuronal differentiation.
      Furthermore, LiCl treatment resulted in a slight, but non-significant increase of
      beta-catenin levels in ES cell-derived embryoid bodies. Our results demonstrate
      that the ES cell test, EST may be suitable to detect inhibitory effects of test
      compounds especially on cardiac differentiation, whereas effects on neuronal
      cells would not be detected. Therefore, we propose that morphological analyses of
      cardiac differentiation alone are insufficient to detect embryotoxic effects. The
      assay of other cell lineages at different developmental stages, and expression
      analyses of tissue-specific genes should also be employed.

PMID- 11330863
TI  - Pattern regulation properties of a Hydra strain which produces additional heads
      along the body axis.
AB  - The multiheaded one (mh-1) strain, isolated from inbred crossings of wild type
      Hydra magnipapillata, develops additional heads along the body axis. This strain
      reproduces asexually by budding like the wild type (wt) does. We found that young
      polyps have a wt-like shape and display wt-like properties. When they grow in
      size and before they produce extra heads along the body axis, the tissue between
      the head and the budding zone changes its property: in this region, where later
      on the extra heads preferentially form, foot regeneration is significantly
      delayed while head regeneration remains unaffected. Further, following various
      transplantations additional heads form under conditions under which the wild type
      did not. The observed changes in pattern control and regulation indicate a two
      step process of pattern formation. Morphogenetic signalling is suggested to cause
      the positional value to increase slowly in the form of patches and preferentially
      in the region between the head and the budding zone. This increase causes an
      altered morphogenetic signalling, which is eventually responsible for additional
      head formation.

PMID- 11330864
TI  - The BMP antagonists cerberus-like and noggin do not interact during mouse
      forebrain development.
AB  - Mouse cerberus-like encodes for a secreted factor of the Cerberus/Dan family.
      This molecule has neural inducing capabilities and can bind to BMP-4 and nodal
      molecules in the extracellular space. When cerberus-like is inactivated, its
      function may be compensated for another molecule, since no abnormalities can be
      observed in the mouse mutant. Compensation mechanisms have been shown to occur
      between the BMP antagonists chordin and noggin. Here we report the generation of
      cerberus-like-/-; noggin-/- double mutants to uncover a possible compensation by
      noggin in cer-l-/- mutant. Double mutants were obtained and failed to show any
      further detectable defects beside the ones presented by the noggin-/- single
      mutant. Contrarily to chordin and noggin, mouse cerberus-like and noggin cannot
      compensate for each other during mouse embryogenesis.

PMID- 11330865
TI  - Expression of the fibroblast activation protein during mouse embryo development.
AB  - Human Fibroblast Activation Protein (FAP), a member of the serine prolyl
      oligopeptidase family, is a type II cell surface glycoprotein that acts as a dual
      specificity dipeptidyl-peptidase (DPP) and collagenase in vitro. Its restricted
      expression pattern in embryonic mesenchyme, in wound healing and in reactive
      stromal fibroblasts of epithelial cancers, has suggested a role for the FAP
      protease in extracellular matrix degradation or growth factor activation in sites
      of tissue remodeling. The FAP homologue in Xenopus laevis has been reported to be
      induced in the thyroid hormone-induced tail resorption program during tadpole
      metamorphosis supporting a role for FAP in tissue remodeling processes during
      embryonic development. However, Fap-deficient mice show no overt developmental
      defects and are viable. To study the expression of FAP during mouse
      embryogenesis, a second Fap-deficient mouse strain expressing beta-Galactosidase
      under the control of the Fap promoter was generated by homologous recombination
      (Fap-/- lacZ mice). FAP deficiency was confirmed by the absence of FAP-specific
      dipeptidyl-peptidase activity in detergent-soluble extracts isolated from 17.5
      d.p.c. Fap-/- lacZ embryos. We report that Fap-/- lacZ mice express beta
      Galactosidase at regions of active tissue remodeling during embryogenesis
      including somites and perichondrial mesenchyme from cartilage primordia.

PMID- 11330866
TI  - Zebrafish keratin 8 is expressed at high levels in the epidermis of regenerating
      caudal fin.
AB  - Cytokeratins are structural proteins of the intermediate filament family and are
      mainly expressed in epithelial cells. In several vertebrates it has been shown
      that keratin 8 is expressed in simple epithelial tissues, some non-epithelial
      tissue and in hyper-proliferative tissues during development and tumor
      transformation. We previously cloned and characterised the zebrafish (Danio
      rerio) homologous cytokeratin 8 cDNA (zfk8) which was described as an epidermal
      marker during zebrafish development. It has been found that the zfk8 gene is
      normally expressed in simple epithelia in embryonic and mature zebrafish. Using
      whole-mount in situ hybridisation, we show in this report that expression of zfk8
      is tightly linked to the regeneration of caudal fin and exclusively observed in
      epidermal cells. It is strongly expressed in the epidermis overlaying the inter
      rays zone of regenerating caudal fin. Our results indicate that in zebrafish,
      cytokeratin 8 is a suitable epidermal marker during regeneration.

PMID- 11330867
TI  - Choice of drug treatment for obesity-related hypertension: where is the evidence?
AB  - Hypertension and obesity are common medical conditions independently associated
      with increased cardiovascular risk. Many large epidemiological studies have
      demonstrated associations between body mass index and blood pressure, and there
      is evidence to suggest that obesity is a causal factor in the development of
      hypertension in obese individuals. Consequently, all hypertension management
      guidelines consider weight reduction as a first step in the management of
      increased blood pressure in obese individuals. Weight reduction may be achieved
      by behaviour modification, diet and exercise, or by the use of anti-obesity
      medications. However, the long-term outcomes of weight management programmes for
      obesity are generally poor, and most hypertensive patients will require
      antihypertensive drug treatment. Some classes of antihypertensive agents may have
      potentially unwanted effects on some of the metabolic and haemodynamic
      abnormalities that link obesity and hypertension, yet most hypertension
      guidelines fail to provide specific advice on the pharmacological management of
      obese patients. This may be because there are currently no studies examining the
      efficacy of specific antihypertensive agents in reducing mortality in obese
      hypertensive patients. This paper reviews the theoretical reasons for the
      differential use of the major classes of antihypertensive agents in the
      pharmacological management of obesity-related hypertension and also considers the
      potential role of anti-obesity agents.

PMID- 11330868
TI  - Antihypertensive mechanisms of lipid-lowering drugs: decoding the Rosetta stone's
      inscriptions'.

PMID- 11330869
TI  - Imaging techniques for non-invasive assessment of coronary heart disease in
      hypertension: value of an integrated approach.

PMID- 11330870
TI  - Mean blood pressure, pulse pressure and grade of hypertension in untreated
      hypertensive patients with sleep-related breathing disorder.
AB  - OBJECTIVE: To test the hypothesis that sleep-related breathing disorder (SRBD) is
      associated with increasing severity of cardiovascular risk markers. DESIGN: A
      cross-sectional study of sleep laboratory patients. SETTING: University Hospital
      Sleep Disorders Centre. PATIENTS: We studied 591 patients referred for a sleep
      study, all of them without a history of systemic hypertension. INTERVENTIONS:
      Clinical interview, two unattended sleep studies, and assessment of office blood
      pressure, cholesterol concentration, alcohol and nicotine consumption and daytime
      blood gases. MAIN OUTCOME MEASURE: Post-hoc analysis of different cardiovascular
      risk markers: mean blood pressure, pulse pressure, and the type and grade of
      systemic hypertension. RESULTS: Patients were classified as normotensive (blood
      pressure < 140/90 mmHg, n = 228) or hypertensive (blood pressure > or = 140/90
      mmHg, n = 363) according to office blood pressure measurements. Mixed (systolic
      and diastolic) hypertension was the most common type of hypertension (n = 182),
      followed by isolated diastolic hypertension (n = 101), borderline isolated
      systolic hypertension (n = 70), and isolated systolic hypertension (n = 10). The
      frequency of mixed hypertension increased with SRBD activity (P < 0.05) and
      respiratory disturbance index (RDI; the number of breathing disorders per hour of
      estimated sleep time) was increased in those with mixed hypertension compared
      with those with normotension (24.8 compared with 15.7; t test: P < 0.01). In
      hypertensive patients classified as having grades 1 -3 of hypertension (n = 265,
      80 and 18, respectively), there was a progressive increase in RDI (18.9, 27.2 and
      30.3, respectively, P < 0.01). Mean blood pressure increased significantly with
      RDI. Pulse pressure increased significantly with age (P < 0.001), but was
      unrelated to the degree of SRBD. CONCLUSION: We conclude that mean blood pressure
      and the severity of hypertension, but not pulse pressure, increase with the
      severity of the SRBD.

PMID- 11330871
TI  - Is coronary risk an accurate surrogate for cardiovascular risk for treatment
      decisions in mild hypertension? A population validation.
AB  - OBJECTIVE: To examine the relationship between coronary (CHD) and cardiovascular
      (CVD) risk in patients with uncomplicated mild hypertension and to determine the
      accuracy of using CHD risk > or = 15% over 10 years to identify for
      antihypertensive treatment those patients with CVD risk > or = 20% over 10 years
      as advised in recent British guidelines. DESIGN: Comparison of decisions made
      using CHD risk > or = 15% over 10 years calculated by the Framingham risk
      function and estimated using a simple table with CVD risk > or = 20% over 10
      years. SETTING: British population. SUBJECTS: People aged 35-64 years with
      uncomplicated mild systolic hypertension (SBP 140-159 mmHg, n = 624) from the
      1995 Scottish Health Survey. MAIN OUTCOME MEASURES: Relationship between CHD and
      CVD risk. Sensitivity, specificity, positive and negative predictive values (PPV
      and NPV). RESULTS: CHD risk 15% over 10 years was equivalent to CVD risk 21% over
      10 years. Exact CHD risk > or = 15% over 10 years had sensitivity 79%,
      specificity 98%, PPV 94% and NPV 93% in detecting CVD risk > or = 20% over 10
      years. Use of the table to estimate CHD risk > or = 15% over 10 years gave
      sensitivity 88%, specificity 90%, PPV 76% and NPV 95%. CONCLUSION: CHD risk
      appears acceptably accurate for targeting treatment in mild hypertension. The
      risk assessment table, which slightly overestimates CHD risk, was more sensitive
      in identifying patients with CVD risk > or = 20% over 10 years and may be
      preferable to using exact CHD risk. European guidelines which suggest targeting
      treatment for mild hypertension at CHD risk > or = 20% over 10 years are over
      conservative compared with British guidelines.

PMID- 11330872
TI  - Placental weight and placental ratio as predictors of later blood pressure in
      childhood.
AB  - OBJECTIVE: A significant inverse relationship between blood pressure and birth
      weight is firmly established. This association may be the result of fetal
      adaptations to an adverse intrauterine environment. Further markers of
      intrauterine growth include the weight of the placenta and the placental ratio
      (the ratio of placental weight to birth weight). A number of studies suggest that
      a decreased placental weight or an elevated placental ratio may be independent
      risk factors for subsequent high blood pressure. The overall evidence for this
      is, however, inconclusive. The purpose of the present study was to clearly define
      the relationships between placental weight, placental ratio and subsequent blood
      pressure during childhood. DESIGN: Prospective cohort study of 2507 singleton
      children, born at term during 1989-1992. Blood pressures were recorded at ages 1,
      3 and 6 years, using a semi-automated oscillometric device. RESULTS: Inverse
      relationships existed between both systolic and diastolic blood pressure and
      placental weight, adjusted for current weight at ages 1, 3 and 6 years. The
      relationships between placental weight and systolic blood pressure were
      statistically significant at ages 1 and 3 years. There was no consistent
      relationship between placental weight and later blood pressure within birth
      weight categories. No clinically or statistically significant association was
      seen between the placental ratio and either systolic or diastolic blood pressures
      at any age. CONCLUSIONS: Birth weight, rather than placental weight or their
      ratio, is the early life factor most importantly related to subsequent blood
      pressure in childhood.

PMID- 11330873
TI  - The smoothness index, but not the trough-to-peak ratio predicts changes in
      carotid artery wall thickness during antihypertensive treatment.
AB  - BACKGROUND: It has recently been demonstrated that the smoothness index (SI) (the
      ratio between the average of the blood pressure changes computed for each hour of
      the recording and its standard deviation), a new and reproducible measure of the
      homogeneity of blood pressure reduction by antihypertensive treatment, has
      evident advantages over trough-to-peak ratio (T/P) in the prediction of the
      regression of left ventricular hypertrophy. Therefore we considered it to be
      worthwhile to compare the ability of SI and T/P to predict changes of the carotid
      artery intima-media thickness (IMT) during pharmacological treatment in patients
      with essential hypertension. METHODS: In 100 patients with essential
      hypertension, 24 h ambulatory blood pressure and carotid artery IMT were measured
      after 3 weeks of therapeutic wash-out and after 12 months of antihypertensive
      treatment (calcium antagonists, diuretics, angiotensin converting enzyme (ACE)
      inhibitors or beta-blockers). The homogeneity of the effect of treatment over
      blood pressure was evaluated by computing T/P and SI. RESULTS: Twenty-four hour
      blood pressure was significantly reduced by therapy, while, on average, a small
      but significant increase in indices of carotid artery wall thickness was
      observed. However, IMT was clearly reduced in patients with high SI.
      Statistically significant correlations were observed between changes in indices
      of carotid artery IMT during therapy and SI. No significant correlation was
      observed between indices of carotid artery morphology and T/P, basal 24 h blood
      pressure or changes in blood pressure during therapy. CONCLUSIONS: SI, but not
      T/P is the predictor of changes in carotid artery wall thickness. The information
      provided by SI is independent from basal blood pressure values. For carotid
      artery morphology, the smoothness of blood pressure reduction is even more
      important than its absolute change.

PMID- 11330874
TI  - Angiotensin-converting enzyme and angiotensinogen gene polymorphisms are non
      randomly distributed in oral contraceptive-induced hypertension.
AB  - OBJECTIVES AND METHODS: Oral contraceptives (OC) usage increases serum
      angiotensinogen levels to three to five times normal and about 5% of these women
      develop arterial hypertension. The genetic contribution to this susceptibility to
      OC-induced hypertension is poorly understood. We have analyzed the genotypes of
      149 hypertensive and 101 normotensive women using oral contraceptives, for three
      genetic polymorphisms in genes of the renin-angiotensin system: an
      insertion/deletion (I/ D) in the angiotensin converting enzyme (ACE) gene, the
      T235M polymorphism of the angiotensinogen gene (AGT) and a point mutation in its
      promoter. RESULTS: After cessation of oral contraception the mean arterial
      pressures of the hypertensive women were separable into two non-overlapping
      groups; 88 of the women remained hypertensive and 61 returned to normal blood
      pressure. Both groups of hypertensive women had a similarly higher frequency of
      hypertensive relatives than the normotensive women, but were otherwise similar.
      The 235T allele of AGT was significantly increased in frequency in the 61 oral
      contraceptive-inducible hypertensive women compared with the controls and the 88
      women that remained hypertensive. The ACE I/D genotypes were similarly
      distributed within the three groups of women, but were distinctly non-random in
      the oral contraceptive-induced hypertensive women when they were also classified
      by AGT genotype. CONCLUSION: This statistical interaction of genotype frequencies
      suggests that the genetic basis of susceptibility to OC-induced hypertension is
      complex.

PMID- 11330875
TI  - Abnormal Ca2+ signalling in vascular endothelial cells from spontaneously
      hypertensive rats: role of free radicals.
AB  - OBJECTIVE: To test the hypothesis that the Ca2+ signal transduction process in
      endothelial cells from genetically hypertensive rats (SHR) is affected by an
      overproduction of free radicals. METHODS: The Ca2+ response to the inositol 1,4,5
      triphosphate (IP3) mobilizing agonist, ATP, was measured using the fluorescent
      probe, fura-2, in endothelial cells from Sprague-Dawley rats, and in young and
      age-matched genetically hypertensive rats (SHR). The effect of free radicals and
      reducing agents on the intracellular release of Ca2+ and IP3productionwas
      determined in resting and ATP-stimulated cells. Experiments were also performed
      to compare the level of expression and enzymatic activity of catalase and
      superoxide dismutase (SOD) in endothelial cells from SHR and Sprague-Dawley rats.
      RESULTS: The exposure of aortic endothelial cells from Sprague-Dawley rats to the
      free-radical generating system, hypoxanthine + xanthine oxidase (HX/XO), caused a
      time- and concentration-dependent inhibition of the ATP-induced Ca2+ response. A
      similar HX/XO-dependent inhibition was also observed in Sprague-Dawley cells
      stimulated with the endoplasmic reticulum Ca2+-ATPase inhibitor, thapsigargin.
      Incubation with the antioxidative enzymes, catalase and SOD, had no effect on the
      ATP-induced Ca2+ release in Sprague-Dawley cells, but led to a strong increase in
      the internal release of Ca2+ in cells from adult (12 weeks old) or young (3 weeks
      old) SHR. The effect of antioxidants was not related either to an enhancement of
      the ATP-induced production of IP3, or to a lower expression and activity of SOD
      and catalase. CONCLUSION: The present work provides evidence that the Ca2+
      signalling process in SHR endothelial cells is affected by an overproduction of
      free radicals, resulting in a depletion of releasable Ca2+ from IP3-sensitive and
      insensitive Ca2+ pools. These results point towards a beneficial action of
      antioxidants on Ca2+ signalling in endothelial cells from models of hypertension.

PMID- 11330876
TI  - Angiotensin II and serotonin potentiate endothelin-1-induced vascular smooth
      muscle cell proliferation.
AB  - BACKGROUND: Vascular smooth muscle cell (VSMC) proliferation induced by various
      growth factors has been implicated in a wide variety of pathological processes,
      including hypertension, atherosclerosis and restenosis after angioplasty.
      OBJECTIVES: To investigate the interactions among well-known potent
      vasoconstrictor substances, endothelin-1 (ET-1), angiotensin II (Ang II), and
      serotonin (5-HT), on VSMC proliferation. METHODS: Growth-arrested rabbit VSMCs
      were incubated with different concentrations of ET-1 in the absence or presence
      of Ang II, 5-HT, or both. VSMC proliferation was examined by increases in
      incorporation of [3H]thymidine into DNA and in cell number. RESULTS: ET-1, Ang II
      and 5-HT stimulated DNA synthesis in a dose-dependent manner. ET-1 had a maximal
      effect at a concentration of 0.5 micromol/l (259% of control), Ang II at 1
      micromol/l (173%), and 5-HT at 50 micromol/l (205%). When added together, ET-1
      (0.1 micromol/l) and Ang II (1 micromol/l) synergistically induced DNA synthesis
      (341%). When the vasoconstrictors were tested in combination, even non-mitogenic
      concentrations of ET-1 (0.01 nmol/l) potentiated 5-HT (5 micromol/l)-induced DNA
      synthesis (404%). Co-incubation of ET-1 (0.01 micromol/l) with Ang II (1
      micromol/l) and 5-HT (5 micromol/l) synergistically induced DNA synthesis (566%).
      These effects on DNA synthesis were paralleled by an increase in cell number. The
      ETA/B non-selective receptor antagonist, TAK044 (1 micromol/l) and the ETA
      receptor antagonist, BQ123 (1 micromol/l), but not the ETB receptor antagonist,
      BQ788 (1 micromol/l), inhibited the mitogenic effect of ET-1 and its interaction
      with Ang II or 5-HT. In addition, TAK044 (1 micromol/l) or BQ123 (1 micromol/l)
      along with the angiotensin II type 1 (AT1) receptor antagonist, candesartan (1
      micromol/l), the 5-HT2A receptor antagonist, sarpogrelate (10 micromol/l), or
      both, inhibited the interactions of ET-1 with Ang II or 5-HT. CONCLUSIONS: Our
      results suggest that Ang II and 5-HT could potentiate ET-1-induced VSMC
      proliferation. Inhibition of ETA, AT1, and 5-HT2A may be effective in the
      treatment of VSMC proliferative disorders associated with hypertension,
      atherosclerosis and restenosis after angioplasty.

PMID- 11330877
TI  - Enhanced superoxide anion formation in vascular tissues from spontaneously
      hypertensive and desoxycorticosterone acetate-salt hypertensive rats.
AB  - OBJECTIVES: To investigate the basal and NADH-stimulated superoxide (.O2-)
      production and inactivation by Cu/Zn superoxide dismutase (SOD) in aorta from
      spontaneously hypertensive rats (SHR) and from desoxycorticosterone acetate
      (DOCA)-salt hypertensive (DOCA-HT) rats. METHODS: Tissue .O2- levels were
      estimated with the lucigenin-enhanced chemiluminescence method in aorta and
      cultured smooth muscle cells (SMCs) from SHR and in aorta from DOCA-HT rats
      treated for 4 weeks. RESULTS: The basal aortic .O2- generation was increased by
      135 and 100%, and the NADH stimulated .O2- production was also increased 37 and
      22% in SHR and in DOCA-HT rats compared to their normotensive controls,
      respectively. Although no difference existed in blood pressure as well as in
      basal and in NADH stimulated .O2- production between Wistar-Kyoto (WKY) rats and
      SHR rats at age of 6 weeks, O2- production and blood pressure increased
      concomitantly in SHR aged 9 and 12 weeks. Basal and NADH-stimulated .O2-
      production, in cultured SMCs, was also 80 and 64% higher, respectively, in SHR
      compared to WKY rats. The NADH oxidase activity was found to be increased in
      aorta from both SHR and DOCA-HT rats but SOD activity was reduced only in aorta
      from DOCA-HT rats. CONCLUSIONS: An enhanced .O2- formation resulting from an
      increased NADH oxidase activity was found in aorta from SHR and DOCA-HT rats.
      Cultured arterial SMCs from SHR also generated excessive .O2- formation under
      basal and stimulated conditions. The age-related increase in vascular .O2-
      formation in association with the rise in blood pressure in SHR suggests that the
      oxidative stress might contribute to the development of hypertension. NADH
      oxidase activity was greater in aorta of both hypertension models, but a decrease
      of Cu/Zn SOD activity could also contribute to the high level of aortic .O2- in
      DOCA-HT rats.

PMID- 11330878
TI  - Bezafibrate reduces heart rate and blood pressure in patients with
      hypertriglyceridemia.
AB  - OBJECTIVE: In hypertriglyceridemic patients, hypertension occurs frequently and
      may be associated with hyperinsulinemia and elevated plasma levels of free fatty
      acids (FFA). Besides the lipid-lowering effects, fibrates have been shown to
      reduce blood pressure in hypertensive patients. The present study was undertaken
      to investigate the effects of bezafibrate on hemodynamics in relation to insulin,
      FFA, sympathetic activity, renal sodium absorption, cyclic-GMP (cGMP) and
      endothelin-1 in hypertriglyceridemic patients. SUBJECTS AND METHODS:
      Hypertriglyceridemic patients (17) were randomized to receive in a double-blind
      placebo-controlled study bezafibrate or placebo for 6 weeks. At the end of both
      treatment periods, blood pressure and heart rate were measured automatically.
      Plasma insulin, FFA, aldosterone, catecholamines, cGMP, endothelin-1 levels and
      24 h urine catecholamines and sodium excretion were assessed. RESULTS:
      Bezafibrate therapy decreased serum triglycerides (-65%, P < 0.001) and
      hemodynamic parameters: heart rate decreased from 69 to 66/min (P = 0.009),
      systolic blood pressure from 137 to 132 mmHg (P = 0.01), diastolic blood pressure
      from 81 to 79 mmHg (P = 0.07) and mean blood pressure from 102 to 99 mmHg (P =
      0.06). Bezafibrate therapy reduced FFA and insulin (-55 and -57% respectively,
      both P < 0.001), while sympathetic activity and renal sodium absorption were not
      affected. cGMP increased (+17%, P = 0.008), whereas endothelin-1 levels tended to
      decrease upon bezafibrate therapy (-10%, P = 0.077) CONCLUSION: Bezafibrate
      reduces heart rate, blood pressure, insulin and FFA in hypertriglyceridemic
      patients. The hemodynamic effects cannot be attributed to changes in sympathetic
      activity or renal sodium absorption. Instead, based on the increase in plasma
      cGMP levels, the bezafibrate-induced hemodynamic effects are most likely to be
      caused by bezafibrate-induced improvement of endothelial function.

PMID- 11330879
TI  - Roles of protein kinase C and Ca2+-dependent signaling in angiotensin II-induced
      adrenomedullin production in rat cardiac myocytes.
AB  - OBJECTIVES: We showed that angiotensin II stimulates adrenomedullin production in
      cultured neonatal rat cardiac myocytes, and that the secreted adrenomedullin
      inhibits hypertrophy of the myocytes, although the intracellular mechanisms of
      adrenomedullin production are still unknown. Since protein kinase C (PKC) and the
      Ca2+ signaling system are involved in cardiac hypertrophy, we examined the roles
      of these intracellular signaling systems in the production of adrenomedullin by
      myocytes. METHODS: Cultured neonatal rat cardiac myocytes were incubated with
      agonists or antagonists of PKC and Ca2+ signaling systems for 24 h.
      Adrenomedullin secreted into the medium and adrenomedullin mRNA expression were
      measured by radioimmunoassay and quantitative polymerase chain reaction,
      respectively. RESULTS: Both phorbol-12-myristate-13-acetate (PMA), a PKC
      activator and A23187, a calcium ionophore, significantly increased adrenomedullin
      mRNA expression and secretion from the myocytes. The induction of adrenomedullin
      secretion by PMA was abolished by H7, a PKC inhibitor, and by downregulation of
      PKC induced by pre-incubation with PMA. Similarly, the stimulation of
      adrenomedullin secretion by 10(-6) mol/l angiotensin II was significantly reduced
      following the inhibition or downregulation of PKC activity in the myocytes.
      Blockade of the L-type Ca2+ channel and chelation of intracellular Ca2+ both
      resulted in a significant reduction of the stimulation of adrenomedullin
      secretion by angiotensin II. In addition, the secretion was significantly
      attenuated by inhibitors of calmodulin (W-7) and calmodulin kinase II (KN-62),
      and slightly attenuated by FK506, a calcineurin inhibitor. CONCLUSIONS: These
      results suggest that PKC and the Ca2+/calmodulin signaling systems are involved
      in angiotensin II-induced adrenomedullin secretion from rat cardiac myocytes.

PMID- 11330880
TI  - Molecular forms of plasma and urinary adrenomedullin in normal, essential
      hypertension and chronic renal failure.
AB  - OBJECTIVES: Human adrenomedullin precursor is converted to glycine-extended
      adrenomedullin (AM-Gly), an intermediate inactive form of adrenomedullin.
      Subsequently, AM-Gly is converted to active form of mature adrenomedullin (AM-m).
      The aim of the present study was to investigate (i) whether sex or age influences
      plasma and urinary AM-m and AM-Gly levels in normal subjects; (ii) the daytime
      variability of plasma AM-m and AM-Gly levels in normal subjects; (iii) AM-m and
      AM-Gly levels and its ratio in plasma and urine in normal subjects, individuals
      with essential hypertension (HT), and chronic renal failure (CRF); and (iv) the
      ratio of AM-m and AM-total (T) in plasma of various veins and aorta. METHODS: We
      measured plasma levels and urinary excretions of AM-m, AM-Gly and AM-T (AM-m + AM
      Gly) by recently developed immunoradiometric assay in normal subjects (n = 81),
      HT (n = 28) and CRF (n = 30). We also determined the molecular forms of plasma
      adrenomedullin taken from various sites during angiography in patients with
      suspected renovascular hypertension (n = 9). RESULTS: There were no differences
      in plasma and urinary excretions of two molecular forms of adrenomedullin among
      sexes or ages in normal subjects. There was no daytime variation of plasma two
      molecular forms of adrenomedullin in normal subjects. Plasma AM-m, AM-Gly and AM
      T levels were increased in patients with HT and CRF compared with normal
      subjects, whereas urinary AM-m, AM-Gly and AM-T excretions were decreased in
      patients with HT and CRF compared with normal subjects. Urinary AM-m: AM-T ratios
      were significantly higher than plasma AM-m: AM-T ratios. Plasma AM-m and AM-T
      levels taken from various veins were similar, and they were significantly higher
      than those of aorta, although there were no differences in plasma AM-Gly levels
      between aorta and veins. CONCLUSIONS: These results suggest that in normal
      subjects, and individuals with HT and CRF: (i) plasma and urinary excretions of
      AM-m and AM-Gly are not affected by age or sex; (ii) AM-m in parallel with AM-Gly
      is increased; (iii) urine contains a higher percentage of active adrenomedullin
      than plasma; and (iv) plasma AM-m may be partly metabolized in the lung.

PMID- 11330881
TI  - Effects of blockade of the renin-angiotensin system on tissue factor and
      plasminogen activator inhibitor-1 synthesis in human cultured monocytes.
AB  - OBJECTIVES: To clarify the pathophysiological significance of the renin
      angiotensin system (RAS) in monocytes, we examined the effect of its blockade on
      tissue factor and plasminogen activator inhibitor-1 (PAI-1) synthesis in human
      cultured monocytes. METHODS: Monocytes were isolated from healthy volunteers and
      cultured. Tissue factor and PAI-1 antigens in culture medium and cells were
      measured by enzyme-linked immunosorbent assay and Western blotting, and mRNA
      levels were assessed by reverse-transcriptase polymerase chain reaction. RESULTS:
      We show that the RAS is present in isolated human peripheral blood monocytes.
      Exogenous angiotensin II increased the levels of tissue factor antigen and mRNA
      in cultured monocytes, but not of PAI-1 synthesis. An angiotensin converting
      enzyme (ACE) inhibitor (captopril) and an angiotensin II type 1 (AT1) receptor
      antagonist (candesartan) decreased the levels of tissue factor protein and mRNA
      in cultured monocytes. These alterations were accompanied by a reduction in the
      levels of tumour necrosis factor-alpha protein and mRNA. The levels of PAI-1
      protein were reduced by captopril, but not by candesartan. A bradykinin B2
      receptor antagonist abolished the suppressive effect of captopril on PAI-1
      antigen. CONCLUSIONS: An ACE inhibitor and an AT1 receptor antagonist reduced
      tissue factor synthesis in these cells. We show different actions of these agents
      on PAI-1 synthesis. ACE inhibition decreased PAI-1 synthesis mediated by
      bradykinin production, but AT1 receptor inhibition had no effect.

PMID- 11330882
TI  - Effect of angiotensin-converting enzyme inhibition on myocardial vascularization
      in the adolescent and adult spontaneously hypertensive rat.
AB  - OBJECTIVE: To determine whether angiotensin-converting enzyme (ACE) inhibition
      treatment enhances myocardial vascularization in adolescent and adult
      spontaneously hypertensive rats (SHRs). METHODS: Male SHRs were treated from 7 to
      14 or from 16 to 24 weeks of age with the ACE inhibitor, perindopril, in either a
      low dose (0.1 mg/kg per day) or a high dose (1 mg/kg per day). Some rats were
      concomitantly treated with a bradykinin antagonist. At termination of treatment,
      the left ventricular wall was extensively sampled and the surface area density
      and length density of myocardial blood vessels stereologically determined.
      RESULTS: High-dose perindopril treatment prevented the development of
      hypertension and left ventricular hypertrophy in adolescent SHRs and markedly
      reduced blood pressure and left ventricular size in adult SHRs. SHRs treated with
      the low dose of perindopril remained hypertensive, although there were
      significant reductions in blood pressure and left ventricular growth. High-dose
      perindopril treatment in adolescent SHRs led to a significant increase in the
      surface area density of blood vessels in the left ventricle after 4 weeks of
      treatment and an increase in both the surface area density and length density of
      blood vessels after 7 weeks of treatment Co-administration with the bradykinin
      antagonist did not reverse these effects. In contrast, ACE inhibitor treatment
      had no effect on myocardial vascularization in adult rats with established
      hypertension. CONCLUSION: ACE inhibitor treatment enhances vascularization in the
      adolescent heart through reductions in myocardial mass, but not capillary growth.
      ACE inhibition in the adult heart with established hypertension reduces left
      ventricular hypertrophy, but does not enhance myocardial capillarization.

PMID- 11330883
TI  - Celiprolol stimulates endothelial nitric oxide synthase expression and improves
      myocardial remodeling in deoxycorticosterone acetate-salt hypertensive rats.
AB  - OBJECTIVE: Endothelium-dependent vasodilation is attenuated in humans and
      experimental hypertension models, and this phenomenon may be largely due to
      decreased release or activity of nitric oxide (NO). However, very few studies
      have evaluated whether beta-adrenoceptor antagonists increase endothelial NO
      synthase (eNOS) expression in the left ventricle. We examined the effects of long
      term treatment with celiprolol, a specific beta1-antagonist with a weak beta2
      agonist action, on eNOS expression in the left ventricle and evaluated its
      relationship to myocardial remodeling in the left ventricle of
      deoxycorticosterone acetate (DOCA)-salt hypertensive rats. METHODS: DOCA-salt
      rats (n = 18) were induced with weekly injections of DOCA (30 mg/kg) and 1%
      saline in their drinking water after right nephrectomy. Celiprolol (DOCA-CEL, n =
      9, 10 mg/kg per day, subdepressor dose) or a vehicle (DOCA-V, n = 9) were given
      after induction of DOCA-salt hypertension for 5 weeks, and age-matched sham
      operated rats (ShC, n = 9) served as a control group. RESULTS: Blood pressure
      levels in DOCA-V and DOCA-CEL were similar and significantly higher than that in
      ShC. The eNOS mRNA and protein levels, and NOS activity in the left ventricle
      significantly decreased in DOCA-V compared with ShC, and significantly increased
      in DOCA-CEL compared with DOCA-V. DOCA-V showed a significant increase in the
      wall-to-lumen ratio, perivascular fibrosis, myocardial fibrosis, and type I
      collagen mRNA, with all these parameters being significantly improved by
      celiprolol. CONCLUSIONS: Myocardial remodeling of DOCA-salt hypertensive rats was
      significantly ameliorated by subdepressor doses of celiprolol, which may be due
      to increased eNOS expression in the left ventricle.

PMID- 11330884
TI  - Chronic bosentan treatment improves renal artery vascular function in diabetes.
AB  - OBJECTIVE: Endothelin-1 (ET-1) has been suggested to play an important role in
      the pathogenesis of diabetes-induced vascular complications. The primary purpose
      of the present study was to examine the potential beneficial effects of chronic
      ET receptor blockade (with bosentan) on vascular function in renal arteries from
      streptozotocin (STZ)-induced diabetic rats. DESIGN: Wistar rats were divided into
      four groups: control (C), control bosentan-treated (CB), diabetic (D) and
      diabetic bosentan-treated (DB). Following 10 weeks of bosentan treatment,
      vascular responses to norepinephrine (NE), ET-1, acetylcholine (ACh) were
      determined in vascular segments of renal arteries, both with and without the
      endothelium denuded, according to the following protocol: (1) a cumulative dose
      response curve (DRC) to NE in the absence and presence of the nitric oxide
      synthase (NOS) inhibitor L-NAME (2) cumulative DRC to ET-1 and (3) cumulative DRC
      to ACh in precontracted arteries. In addition, plasma ET-1 was assayed and ET-1
      like immunoreactivity was determined in vascular tissues by immunohistochemistry.
      RESULTS: The maximum contractile responses to NE and ET-1 were markedly
      exaggerated in endothelium-intact renal arteries from untreated D rats while ACh
      responses were preserved. Arteries denuded of endothelium did not exhibit
      exaggerated responses to NE or ET-1. L-NAME treatment did not affect responses to
      NE in arteries with or without endothelium. Strikingly, responses to NE and ET-1
      (in arteries with endothelium) were completely normalized following long-term
      bosentan treatment. In addition, plasma ET-1 levels did not differ between C and
      D groups. However, renal arteries isolated from the D group exhibited increased
      ET-1-like immunoreactivity (local ET-1 content). CONCLUSION: These data uncover,
      for the first time, beneficial effects of mixed ETA/ETB receptor blockade on
      renal artery vascular function in diabetes. Alterations in the production and/or
      action of ET-1 may have important implications in the development of vascular
      dysfunction in experimental diabetes.

PMID- 11330885
TI  - Pulse wave velocity as endpoint in large-scale intervention trial. The Complior
      study. Scientific, Quality Control, Coordination and Investigation Committees of
      the Complior Study.
AB  - OBJECTIVE: To evaluate the ability of an antihypertensive therapy to improve
      arterial stiffness as assessed by aortic pulse wave velocity (PWV) in a large
      population of hypertensive patients. SETTING: Sixty-nine healthcare centres,
      private and institutional (19 countries). PATIENTS: Subjects aged 18-79 years,
      with essential hypertension. A total of 2,187 patients were enrolled; 1,703 (52%
      male) completed the study: mean age = 50 +/- 12 years; mean baseline
      systolic/diastolic blood pressure (S/D BP) = 158 +/- 15/98 +/- 7 mmHg; mean
      baseline carotid-femoral PWV = 11.6 +/- 2.4 m/s. INTERVENTIONS: Patients were
      treated for 6 months, starting with perindopril (angiotensin converting enzyme
      (ACE) inhibitor) 4 mg once daily (OD), increased to 8 mg OD, and combined to
      diuretic (indapamide 2.5 mg OD) if BP was uncontrolled (> 140/90 mmHg). RESULTS:
      It was feasible to measure carotid-femoral PWV using the automatic device
      Complior at inclusion, 2 and 6 months, along with conventional BP assessments in
      a population of 1,703 patients. Significant decreases (P < 0.001) in BP
      (systolic: -23.7 +/- 16.8, diastolic: -14.6 +/- 10 mmHg), and carotid-femoral PWV
      (-1.1 +/- 1.4 m/s) were obtained at 2 and 6 months. CONCLUSIONS: The Complior
      Study is the first study to show the feasibility of a large-scale intervention
      trial using PWV as the endpoint in hypertensive patients. Adequate results may be
      obtained using an automatic device and rigorous criteria for assessment. A long
      term controlled intervention study is needed to confirm the results of the
      present uncontrolled trial.

PMID- 11330886
TI  - Risk assessment and treatment benefit in intensively treated hypertensive
      patients of the hypertension Optimal Treatment (HOT) study.
AB  - BACKGROUND: The Hypertension Optimal Treatment (HOT) Study provided information
      about cardiovascular events in 18,790 hypertensives, subjected to pronounced
      blood pressure lowering for a mean of 3.8 years. METHODS AND RESULTS: The HOT
      Study data have been further analysed after risk stratification of the patients
      (1999 World Health Organization and International Society of Hypertension
      guidelines criteria): (i) no patients of the HOT Study were classified as low
      risk, 50% were classified as medium risk, 20.2% as high risk and 29.8% as very
      high risk; (ii) incidence of cardiovascular events in these patients with
      excellent blood pressure control [92% had diastolic blood pressure (DBP) < or =
      90 mmHg] remained proportional to pretreatment risk. The relative risk of very
      high- versus medium-risk strata was between two and three both when HOT Study
      patients were considered independently of, or within the DBP target group they
      had been randomized to; and (iii) event rates in all risk strata were calculated
      to be much lower (possibly 60% lower) than rates expected from baseline risk
      calculated approximately by the Framingham equation. CONCLUSIONS: The low event
      rate in HOT Study patients is likely to result from pronounced blood pressure
      lowering, and is not explained by a lower risk profile than in previous
      controlled trials of antihypertensive treatment. The persistence of a risk
      gradient despite intensive blood pressure lowering suggests a combination of
      blood pressure control with other strategies of risk correction and the need to
      initiate antihypertensive therapy before complications develop.

PMID- 11330887
TI  - Impact of pulse pressure on degree of cardiac hypertrophy in patients with
      chronic uraemia.

PMID- 11330889
TI  - Chemical synthesis of linear and cyclic unnatural oligosaccharides by iterative
      glycosidation of ketoses.
AB  - The development of an efficient method for the stereoselective synthesis of alpha
      D-(2-->1)-linked ketoside oligomers is described. The method is based on an
      iterative protocol composed of two key steps: a) the coupling of a
      thiazolylketosyl phosphite donor with an hydroxymethylketoside acceptor; and b)
      the introduction of the hydroxy-methyl group at the anomeric carbon atom of the
      resulting oligomer. To highlight its efficiency, the protocol was used in the
      assembly of D-galacto-2-heptulopyranose-containing oligoketosides through alpha
      (2-->1) linkages up to the pentameric stage. The yield of the isolated oligomers
      ranged from 48 % in the first cycle to 29% in the fourth cycle. Having employed a
      pentenyl-substituted hydroxymethylketoside acceptor in the first cycle, all the
      derived oligomers contained the pentenyl group at their reducing end. This group
      was exploited to transform the linear oligomers into cyclic products through
      intramolecular glycosidation. The major product derived from the linear
      trisaccharide was confirmed by X-ray crystallography to be the cyclotris-(2-->1)
      (alpha-D-galacto-2-heptulopyranosyl). The structure of this compound was
      essentially that of a [9]crown-3 ether bearing three galactopyranose rings
      spiroanellated in a propellerlike fashion. This arrangement of carbohydrate units
      linked to the crown ether created a densely alkoxylated cavity suitable for the
      encapsulation of alkali-metal cations (Li, Na, K, Ca, Mg).

PMID- 11330888
TI  - Structure-activity correlation between natural glutathione peroxidase (GPx) and
      mimics: a biomimetic concept for the design and synthesis of more efficient GPx
      mimics.
AB  - Among the organoselenium compounds that mimic the action of the natural enzyme
      glutathione peroxidase (GPx), there are certain basic differences in the
      activity, substrate specificity and mechanism. These differences arise mainly
      from the nature of the substituents near the reaction center, and stability and
      reactivity of the intermediates. As an attempt to draw some general concepts for
      the development of new mimics, a structure - activity correlation between natural
      GPx and some existing mimics is described.

PMID- 11330890
TI  - Relaxivity and water exchange studies of a cationic macrocyclic gadolinium(III)
      complex.
AB  - We conducted relaxometric and water exchange studies of the cationic
      [Gd((S,S,S,S)-THP)(H2O)]3+ complex (THP 1,4,7,10-tetrakis(2-hydroxy-propyl)
      1,4,7,10-tetraazacyclododecane). While the NMRD profiles obtained are typical for
      DOTA-like complexes (DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10
      tetraacetate), variable-temperature 7O NMR investigations revealed a relatively
      high water exchange rate (k(298)(ex) = 1.89 x 10(7) s(-1)). These results differ
      from those reported for other cationic tetraamide macrocyclic Gd(III) complexes,
      which exhibit characteristically low exchange rates. Since the low exchange rates
      are attributed partially to the geometry of the M isomer (square antiprismatic)
      in the tetraamide derivatives, the atypical water exchange rate observed in
      [Gd((S,S,S,S)-THP-(H2O)]3+ may result from a twisted square antiprismatic
      structure in this complex and from the relatively high steric strain at the water
      coordination site as a result of the presence of methyl groups at the alpha
      position with respect to the Gd(III)-bound O atoms of THP.

PMID- 11330891
TI  - A polyrotaxane series containing alpha-cyclodextrin and naphthalene-modified
      alpha-cyclodextrin as a light-harvesting antenna system.
AB  - Supramolecular light-harvesting antenna systems were constructed by using
      polyrotaxanes, in which cyclodextrin (CD) rings of alpha-CD and naphthalene
      (energy donor)-appended alpha-CD are threaded by a poly(ethylene glycol) chain
      with anthracene (energy acceptor) units at both ends (5-8). The effects of the
      component ratio of the polyrotaxanes on the efficiencies of energy migration and
      energy transfer were examined by fluorescence emission and excitation spectra and
      anisotropy and by fluorescence decay measurements. The observed results were
      explained by using the Forster mechanism.

PMID- 11330892
TI  - The energetic and structural effects of steric crowding in phosphate and
      dithiophosphinate complexes of lanthanide cations M3+: a computational study.
AB  - Metal-ligand binding strength and selectivity result from antagonistic metal
      ligand M-L attractions and ligand-ligand L-L repulsions. On the basis of quantum
      mechanical (QM) calculations on lanthanide complexes, we show that this interplay
      determines the binding affinities in the gas phase. In the series of [ML3]
      complexes (M = La, Eu, and Yb) with negatively charged phosphoryl ligands L- =
      (MeO)2PO2- and Me2PS2-, the binding energies follow the order Yb3+ > Eu3+ > La3-
      for a given ligand, and (MeO)2PO2- > Me2PS2- for a given cation. However, adding
      a neutral LH ligand to [ML3] changes the order to Eu3+ > Yb3+ > La3+ for the
      oxygen ligand and La3+ > Eu3- > Yb3+ for the sulfur ligand, indicating that
      steric strain in the first coordination sphere is largest for the smallest cation
      and for sulfur binding sites. We investigated the question of additional
      hydration of the [ML3LH] complexes in aqueous solution by molecular dynamics (MD)
      simulations, using two sets of atomic charges. It was found that pairwise
      additive potentials overestimate the coordination and hydration numbers of the
      cations, while adding polarization energy terms for the ligands yields better
      agreement between QM and MD results and supports the concept of steric strain in
      the first coordination sphere.

PMID- 11330893
TI  - Structural effects on the OH-promoted fragmentation of methoxy-substituted 1
      arylalkanol radical cations in aqueous solution: the role of oxygen acidity.
AB  - A kinetic and product study of the OH- -induced decay in H2O of the radical
      cations generated from some di-and tri-methoxy-substituted 1-arylalkanols
      (ArCH(OH)R*+) and 2- and 3-(3,4-dimethoxyphenyl)alkanols has been carried out by
      using pulse- and gamma-radiolysis techniques. In the 1-arylalkanol system, the
      radical cation 3,4-(MeO)2C6H3CH2-OH*+ decay at a rate more than two orders of
      magnitude higher than that of its methyl ether; this indicates the key role of
      the side-chain OH group in the decay process (oxygen acidity). However, quite a
      large deuterium kinetic isotope effect (3.7) is present for this radical cation
      compared with its a-dideuterated counterpart. A mechanism is suggested in which a
      fast OH deprotonation leads to a radical zwitterion which then undergoes a rate
      determining 1,2-H shift, coupled to a side-chain-to-ring intramolecular electron
      transfer (ET) step. This concept also attributes an important role to the energy
      barrier for this ET, which should depend on the stability of the positive charge
      in the ring and, hence, on the number and position of methoxy groups. On a
      similar experimental basis, the same mechanism is suggested for 2,5
      (MeO)2C6H3CH2OH*+ as for 3,4-(MeO)2C6H3CH2OH*+, in which some contribution from
      direct C-H deprotonation (carbon acidity) is possible. In fact, the latter
      process dominates the decay of the trimethoxylated system 2,4,5-(MeO)3C6H2CH2
      OH*+, which, accordingly, reacts with OH- at the same rate as that of its methyl
      ether. Thus, a shift from oxygen to carbon acidity is observed as the positive
      charge is increasingly stabilized in the ring; this is attributed to a
      corresponding increase in the energy barrier for the intramolecular ET. When
      R=tBu, the OH- -promoted decay of the radical cation ArCH(OH)R*+ leads to
      products of C-C bond cleavage. With both Ar = 3,4- and 2,5-dimethoxyphenyl the
      reactivity is three orders of magnitude higher than that of the corresponding
      cumyl alcohol radical cations; this suggests a mechanism in which a key role is
      played by the oxygen acidity as well as by the strength of the scissile C-C bond:
      a radical zwitterion is formed which undergoes a rate-determining C-C bond
      cleavage, coupled with the intramolecular ET. Finally, oxygen acidity also
      determines the reactivity of the radical cations of 2-(3,4
      dimethoxyphenyl)ethanol and 3-(3,4-dimethoxyphenyl)propanol. In the former the
      decay involves C-C bond cleavage, in the latter it leads to 3-(3,4
      dimethoxyphenyl)propanal. In both cases no products of C-H deprotonation were
      observed. Possible mechanisms, again involving the initial formation of a radical
      zwitterion, are discussed.

PMID- 11330894
TI  - (MeLi)4(dem)1.5]infinity] and [(thf)3Li3M3[(NtBu)3S--how to reduce aggregation of
      parent methyllithium.
AB  - Organolithium compounds play the leading role among the organometallic reagents
      in synthesis and in industrial processes. Up to date industrial application of
      methyllithium is limited because it is only soluble in diethyl ether, which
      amplifies various hazards in large-scale processes. However, most reactions
      require polar solvents like diethyl ether or THF to disassemble parent
      organolithium oligomers. If classical bidentate donor solvents like TMEDA (TMEDA=
      N,N,N',N'tetramethyl-1,2-ethanediamine) or DME (DME=1,2-dimethoxyethane) are
      added to methyllithium, tetrameric units are linked to form polymeric arrays that
      suffer from reduced reactivity and/or solubility. In this paper we present two
      different approaches to tune methyllithium aggregation. In
      [[(MeLi)4(dem)1,5)infinity] (1; DEM = EtOCH2OEt, diethoxymethane) a polymeric
      architecture is maintained that forms microporous soluble aggregates as a result
      of the rigid bite of the methylene-bridged bidentate donor base DEM. Wide
      channels of 720 pm in diameter in the structure maintain full solubility as they
      are coated with lipophilic ethyl groups and filled with solvent. In compound 1
      the long-range Li3CH3...Li interactions found in solid [[(MeLi)4]infinity] are
      maintained. A different approach was successful in the disassembly of the
      tetrameric architecture of [((MeLi)4]infinity]. In the reaction of dilithium
      triazasulfite both the parent [(MeLi)4] tetramer and the [[Li2[(NtBu)3S]]2] dimer
      disintegrate and recombine to give an MeLi monomer stabilized in the adduct
      complex [(thf)3Li3Me-[(NtBu)3S]] (2). One side of the Li3 triangle, often found
      in organolithium chemistry, is shielded by the tripodal triazasulfite, while the
      other face is mu3-capped by the methanide anion. This Li3 structural motif is
      also present in organolithium tetramers and hexamers. All single-crystal
      structures have been confirmed through solid-state NMR experiments to be the same
      as in the bulk powder material.

PMID- 11330895
TI  - A new class of dianionic sulfur-ylides: alkylenediazasulfites.
AB  - The compounds [[(thf)Li2-[H2CS(NtBu)2]]2] (1) and [((thf)Li2[(Et)
      (Me)CS(NtBu)2])2] (2) can be synthesized in a two-step reaction. Firstly addition
      of an alkyllithium to sulfur diimide gives the diazaalkylsulfinate [RS(NtBu)2] (R
      =Me, sBu). In a second step the alpha-carbon atom in R is metalated with one
      equivalent of methyllithium to give the S-ylides. This new class of compounds can
      be rationalized as sulfite analogues, in which two oxygen atoms are each
      isoelectronically replaced by a NtBu group and the remaining oxygen atom is
      replaced by a CR2 group. Similar to Corey's S-ylides (R2(O)S+-CR2) and Wittig's
      phosphonium ylides (R3P+ - -CR2), these molecules contain a positively charged
      sulfur atom next to a carbanionic center. Therefore nucleophilic addition
      reactions of the carbon atom are feasible. The reaction of a sulfur diimide with
      the anionic carbon center in [H2CS-(NtBu)2]2- gives the intermediate
      alkylbis(diazasulfinate) [(tBuN)2SCH2S(NtBu)2]2-. The acidity of the hydrogen
      atoms at the bridging CH2 group is high enough to give, upon deprotonation, the
      [(tBuN)2SCHS(NtBu)2]3- trianion in [[(thf)Li3[(tBuN)2SCHS(NtBu)2]]2] (3). In
      [(Et)(Me)CS(NtBu)2]2 the nucleophilic carbon atom is sterically hindered and
      transimidation instead of deprotonation is observed. In a complex redox process
      [(thf)6Li6S((NtBu)3S]2] is recovered. The two new classes of compounds broaden
      the rich coordination chemistry of the triazasulfites by the introduction of a
      hard carbon center.

PMID- 11330896
TI  - Remote dipole effects as a means to accelerate [Ru(amino alcohol)]-catalyzed
      transfer hydrogenation of ketones.
AB  - A new generation of 2-aza-norbornyl amino alcohol ligands for the catalytic
      transfer hydrogenation reaction of aromatic ketones was synthesized. Extremely
      active catalysts were formed by introducing a ketal functionality at the rear end
      of the ligand. Acetophenone was reduced in 96% ee at low catalyst loading,
      substrate to catalyst ratio, S/C 5000, within 90 minutes with isopropyl alcohol
      as the hydrogen donor. It was found that the dioxolane substituent in the ligand
      increased the turnover frequency, TOF50, from 1050 h(-1) to 3000 h(-1) at an S/C
      ratio of 1000. Introduction of a methyl group at the carbinol carbon resulted in
      TOF50 as high as 8500 h(-1). Transfer hydrogenation of a range of aromatic
      ketones was evaluated and found to reach completion within 30 minutes at room
      temperature, and excellent enantioselectivity, up to 99 % ee, was obtained. A
      possible explanation for the enhanced activity was provided by density functional
      calculations, which showed that the presence of a remote dipole in the ligand
      lowered the transition state energy.

PMID- 11330897
TI  - One-step synthesis of a highly active, mesoporous, titanium-containing silica by
      using bifunctional templating.
AB  - A highly active, three-dimensional, mesoporous titanosilica, TiTUD-1, with
      comparable properties to Ti-grafted mesoporous silica MCM-41, has been prepared
      in a one-step synthesis. A non-surfactant chemical, triethanolamine, was used as
      a template molecule. Triethanolamine easily forms complexes with titanium
      alkoxides, yielding titanatrane complexes, which together with free
      triethanolamine form meso-sized aggregates that template mesopores upon
      increasing the temperature of the synthesis mixture. Triethanolamine served as
      both mesopore template and ligand for the titanium complexes, which represent the
      majority of the catalytic-site precursors. The formation of the silica network
      and the titanium insertion were followed by a combination of diffuse reflectance
      UV/ Vis/NIR and FTIR spectroscopy. A titanium-rich phase was obtained on the
      mesopore surfaces during calcination, allowing for easy accessibility of the
      reactants to the catalytic sites. TiTUD-1 is about six times more active than
      framework-substituted Ti-MCM-41 and has similar activity to Ti-grafted MCM-41.

PMID- 11330898
TI  - Transition from the layered Sr2RhO4 to the monodimensional Sr4RhO6 phase.
AB  - Study of the structural changes occurring during the reduction process of the
      Sr2RhO4+delta, (214), n=1 term of the Ruddlesden and Popper series, shows that
      for delta <0.02 values, this material dissociates into the Sr4RhO6 (416)
      monodimensional phase, alpha = infinity, beta = 0 compound of the (A3B2O6)alpha
      (A3B3O9)beta family, and Rh metal. During the first stage, this process occurs by
      the formation of an intergrowth between the (214) and (416) materials which can
      be only detected by high resolution electron microscopy and is easily interpreted
      on the basis of the structural relationship established between them. Further
      reduction allows the segregation of both phases as separated entities, which
      coexist with Rh metal. The dissociation process is reversible and, under
      oxidizing conditions, a layered material with anionic composition delta =0.06 is
      always obtained. This behaviour seems to be a general way of accommodating the
      compositional changes in layered A2BO4 phases where the B cation is always in a
      octahedral environment. The structural mechanism of this transformation is
      proposed, and the structural relationship between these two low-dimensional
      oxides is established.

PMID- 11330899
TI  - A quantum-mechanical description of macrocyclic ring rotation in benzylic amide.
AB  - Catenanes can undergo rotation of one ring through the cavity of the other. Since
      macroscopic and molecular properties must clearly vary with the relative
      positions and orientations of the interlocked components, a complete
      understanding of the way that the rings rotate is of considerable importance.
      Here we show that low-dimensional quantum-mechanical modeling can yield rate
      constants and barriers similar to those obtained by temperature-dependent nuclear
      magnetic resonance experiments. Data from both non-hydrogen bond disrupting (e.g.
      CDCl3) and hydrogen bond disrupting (e.g. [D6]DMSO) solvents are well reproduced
      demonstrating the validity of the model. The successful simulation of the rates
      of circumrotations by entirely harmonic transition state theory originates from
      the description of the anharmonic levels of the systems through an effective
      harmonic frequency, not very different from twice the zero point energy. The
      nature of the model makes it extendable, in principle, to the calculation of
      properties dependent upon circumrotational activity.

PMID- 11330900
TI  - Imide--amide rearangement of cylic phosphorimidates: a mechanistic study.
AB  - Studies aimed at the development of new synthetic pathways for the preparation of
      chiral cyclic oxaza and diaza phosphoramides suitable for use in asymmetric
      chemistry led us to the investigation of the imide -amide rearrangement of cyclic
      phosphorimidates. As a result of this work new types of oligomeric
      organophosphorus compounds, formed by a novel 1,4-addition type ring opening
      polymerisation, were identified. These compounds are the stable intermediates of
      the imide-amide rearrangement, which upon heating yield the previously reported
      rearranged product. A detailed study of the mechanism of the Lewis acid catalysed
      imide-amide rearrangement and stereochemical control of the final products is
      reported. As a result, the full mechanism was elucidated and evidence of
      retention of configuration at the rearranged carbon atom is presented.
      Substituent effects were rationalised based on molecular modelling calculations.

PMID- 11330901
TI  - Reduction of dioxygen by a dimanganese  unit bonded inside a cavity provided by a
      pyrrole-based dinucleating ligand.
AB  - A novel class of dinucleating ligands has been introduced into manganese
      chemistry to study the reactivity of this metal towards dioxygen under strictly
      controlled conditions. Such N4 ligands combine some of the major peculiarities of
      tetradentate Schiff bases and the porphyrin skeleton. They are derived from the
      condensation between 2-pyrrolaldehyde and ethylenediamine or o-phenylenediamine,
      leading to pyrenH2 (LH2, 1), pyrophenH2 (L'H2, 2) and Me2pyrophenH2, (L"H2, 3),
      respectively. Their metallation with [Mn3-(Mes)6] (Mes = 2,4,6-trimethylphenyl)
      led to [Mn2L2] (4), [MnL'(thf)2] (5) and [MnL"(thf)2] (6). Complex 4 displays a
      double-stranded helical structure, while 5 and 6 are mononuclear complexes
      containing hexacoordinated metals. Regardless of their structure, complexes 5 and
      6 behave in a similar manner to 4 in their reaction with dioxygen, namely, as a
      dimetallic unit inside a cavity defined by two dinucleating ligands. These
      reactions led to dinuclear MnIII/MnIV oxo-hydroxo derivatives, [Mn2L2(mu-O)(mu
      OH)] (7), [Mn2L'2(mu-O)(mu-OH)] (8) and [Mn2L"2(mu-O)(mu-OH)] (9), in which the
      two Mn ions are strongly antiferromagnetically coupled [J = -53 (7), J = -64 (8),
      J = -60 cm(-1) (9)]. The crystal structure of 7 could only be solved with
      synchrotron radiation as the crystals diffracted very poorly and suffered from
      twisting and disorder. The formation of 7-9 has been proposed to occur through
      the formation of an intermediate dinuclear hydroperoxo species.

PMID- 11330902
TI  - Solid state and solution conformation of [Ala7]-phalloidin: a synthetic
      phallotoxin analogue.
AB  - Phallotoxins are toxic compounds produced by poisonous mushroom Amanita
      phalloides and belong to the class of bicyclic peptides with a transannular
      thioether bridge. Their intoxication mechanism in the liver involves a specific
      binding of the toxins to F-actin that, consequently, prevents the
      depolymerization equilibrium with G-actin. Even though the conformational
      features of phallotoxins have been worked out in solution, the exact mechanism of
      interaction with F-actin is still unknown. In this study a toxic phalloidin
      synthetic derivative, bicyclo(Ala1-D-Thr2-Cys3-cis-4-hydroxy-Pro4-Ala5-2-mercapto
      Trp6-Ala7)(S-3-->6) has been synthesized. A substitution at position 7. with an
      Ala residue replaces the 4,5-dihydroxy-Leu present in the natural phalloidin.
      This analogue has formed crystals suitable for X-ray analysis, and represents the
      first case for such a class of compounds. The solid-state structure as well as
      the solution conformation have been evaluated. NMR techniques have been used to
      extract interproton distances as restraints in subsequent molecular dynamics
      calculations. Finally, a direct comparison between structures in solution and in
      the solid state is presented.

PMID- 11330903
TI  - Structural features and molecular assembly of amorphous phosphazenic materials in
      the bulk--combined theoretical and experimental techniques: Tris-(2,2'-dioxy-1,1'
      binaphthyl)cyclotriphosphazen.
AB  - The structure and the assembly of tris-(2,2'-dioxy-binaphthyl)cyclotriphosphazene
      [(+)-[NP3(O2C20H12)3], DBNP, in the solid amorphous state was studied using
      molecular dynamics (MD) including ad hoc quantum mechanically derived force field
      (FF) parameters, in combination with the energy dispersive X-ray diffraction
      (EDXD) technique. The atom-atom radial distribution function (RDF) curve obtained
      through the EDXD experiment revealed low intensity peaks not attributable to the
      intramolecular distances of the single molecule, but clearly featuring a low
      energy state of long-distance three-dimensional assembly. The radial distribution
      functions (RDF) were calculated for various models of DBNP submitted to
      theoretical MD simulations. Based on the comparison of theoretically calculated
      RDFs and those obtained from the EDXD experiment, the predominant structural
      motif of the material in the bulk was found to have DBNP molecules laid one upon
      the other to form tubular nanostructures. These contain eight DBNP units each
      (length ca. 46 A) with two and three of these units aligned in parallel and held
      together. The material can be represented as a bulk of tubular snake-like chains
      undergoing distortions with a step of eight DBNP units. The bending angles, that
      vary randomly, attain limited values sufficient to induce disorder and thus
      nonperiodic structure. The present application of MD simulations combined with
      EDXD data appear to be a general approach to solve for the first time otherwise
      intractable issues concerning structural features and assembly of molecular
      materials in the bulk.

PMID- 11330904
TI  - Determination of interconversion barriers by dynamic gas chromatography:
      epimerization of chalcogran.
AB  - The four stereoisomers of chalcogran 1 ((2RS,SRS)-2-ethyl-1,6-di
      oxaspiro[4.4]nonane), the principal component of the aggregation pheromone of the
      bark beetle pityogenes chalcographus, are prone to interconversion at the spiro
      center (C5). During diastereo- and enantioselective dynamic gas chromatography
      (DGC), epimerization of 1 gives rise to two independent interconversion peak
      profiles, each featuring a plateau between the peaks of the interconverting
      epimers. To determine the rate constants of epimerization by dynamic gas
      chromatography (DGC), equations to simulate the complex elution profiles were
      derived, using the theoretical plate model and the stochastic model of the
      chromatographic process. The Eyring activation parameters of the experimental
      interconversion profiles, between 70 and 120 C in the presence of the chiral
      stationary phase (CSP) Chirasil-beta-Dex, were then determined by computer-aided
      simulation with the aid of the new program Chrom-Win: (2R,5R)-1: deltaG(++)
      (298.15 K) = 108.0 +/-0.5 kJ mol(-1), deltaH(++) = 47.1+/-0.2 kJ mol(-1),
      deltaS(++) = -204+/-6 JK(-1) mol(-1): (2R,5S)-1: deltaG(++) (298.15 K) = 108.5+/
      0.5 kJ mol(-1), deltaH(++) = 45.8+/-0.2 kJ mol(-1), deltaS(++) = -210 +/-6 J K
      mol(-1); (2S,5S)-1: deltaG(++) (298.15 K)= 108.1+/-0.5 kJ mol(-1), deltaH(++) =
      49.3+/-0.3 kJ mol(-1), deltaS(++) = -197+/-8 J K(-1) mol(-1); (2S,5R)-1:
      deltaG(++) (298.15 K)=108.6+/-0.5 kJ mol(-1), deltaH(++) = 48.0+/-0.3 kJ mol(-1),
      deltaS(++) = -203+/-8 J K(-1) mol(-1). The thermodynamic Gibbs free energy of the
      E/Z equilibrium of the epimers was determined by the stopped-flow
      multidimensional gas chromatographic technique: deltaG(E/Z) (298.15 K)= -0.5 kJ
      mol(-1), deltaH(E/Z) = 1.4 kJ mol(-1) and deltaS(E/Z) = 6.3 J K(-1) mol(-1). An
      interconversion pathway proceeding through ring-opening and formation of a
      zwitterion and an enol ether/alcohol intermediate of 1 is proposed.

PMID- 11330905
TI  - Change of the reaction pattern by methodological variations in a multicomponent
      assembly promoted by Ni complexes.
AB  - The pi-allylnickel complex formed by the addition of trimethylsilyl chloride
      (TMSCl) to a mixture of [Ni-(cod)2] (cod = 1,5-cyclooctadiene) and a vinyl ketone
      (Mackenzie complex) carbometalates an acetylene in a completely regioselective
      manner resulting in the formation of the corresponding vinyl nickel species. This
      intermediate is capable of controlled quenching in a variety of ways to give
      different types of compounds: under a CO atmosphere, an acylnickel species is
      formed that ensues from the carbometalation of the enol ether double bond to form
      cyclo-pentenone derivatives. Alternatively, if acetylene is present in excess and
      CO is absent, another acetylene moiety will replace the CO and cyclohexadienes
      will result instead. Finally, if only an excess of the vinyl ketone is used, the
      product from a slow double addition of the vinyl ketone across the triple bond is
      formed. The regioselectivities obtained by the present method are different from
      those obtained by the involvement of nickel acyclopentadienes as intermediates
      when the order of addition is reversed.

PMID- 11330906
TI  - Synthesis of aluminum hydrazides by hydroalumination of 2,3-diazabutadienes-
      formation of an Al4(N2)3 cage compound and an Al3(N2)3 macrocyclic ligand.
AB  - Treatment of 1,1,4,4-tetramethyl-2,3-diazabutadiene with the alane adduct
      [AlH3(NMe2Et)] yielded the hydrazine derivative (AlH2)2-(AlH)2(N2iPr2)3 (1) by
      the hydroalumination of both C N double bonds. Compound 1 has a complicated cage
      structure formed by three hydrazido groups and four aluminium atoms. As a
      particularly interesting structural motif it contains a N-N group side-on
      coordinated to one aluminium atom through its lone pairs of electrons.
      Sublimation of 1 gave a heterocubane-type compound (HAlNiPr)4 (2) by the complete
      cleavage of all N-N bonds, one face of which is bridged by weakly coordinated
      diisopropyldiazene with a N-N double bond. Repeated sublimation gave the pure,
      unsupported heterocubane molecule 3. Heating of the rough product of the reaction
      of alane and diazabutadiene to 90 degrees C in a closed vessel yielded another
      product Al(AlH2)3(N2iPr2)3 (4), which contains a cyclic chelating ligand formed
      by three hydrazido groups and three aluminium atoms. This heterocycle coordinates
      a fourth aluminum atom in the molecular center by close contacts to all six
      nitrogen atoms. A strongly flattened, distorted octahedral coordination sphere
      results for the inner metal atom.

PMID- 11330907
TI  - A G2 study of SH+ exchange reactions involving lone-pair donors and unsaturated
      hydrocarbons.
AB  - The ligand exchange reactions between mono-adducts of the sulfenium ion ([SH-X]-)
      and either unsaturated hydrocarbons or lone-pair donors have been investigated
      computationally at the G2 level. The mono-adducts react with acetylene or
      ethylene to form a thiiranium or a thiirenium ion, in most cases without an
      overall barrier. In the reactions involving lone-pair donors, the original lone
      pair donor is expelled from the [SH-X]- mono-adduct with the formation of a new
      mono-adduct. The reaction proceeds in this case via an intermediate di-adduct.
      Both the hydrocarbon and the lone-pair donor attack the mono-adduct with the
      relevant orbitals aligned in a near-collinear fashion, as was also the case for
      previously investigated reactions involving PH2+ and Cl+. The reaction energies
      and the binding energies of the intermediate complexes in the exchange reactions
      are primarily determined by the electronegativities of the lone-pair donors. The
      thermochemical data can be rationalized within the framework of qualitative
      molecular orbital theory, and the results are compared with our previous findings
      for the corresponding reactions involving PH2+ and Cl+.

PMID- 11330908
TI  - Facilitated olefin transport by reversible olefin coordination to silver ions in
      a dry cellulose acetate membrane.
AB  - The highly selective dry complex membrane AgBF4-cellulose acetate (CA) was
      prepared and tested for the separation of ethylene/ethane and propylene/propane
      mixtures. The maximum selectivity for olefin over paraffin was found to be 280
      for the ethylene/ethane mixture and 200 for the propylene/propane mixture. Solid
      state interactions of AgBF4 with cellulose acetate (CA) and/or olefins have been
      investigated by using FT-IR, UV, and X-ray photoelectron spectroscopy (XPS). FT
      IR and XPS studies clearly show that the silver ions are coordinated by carbonyl
      oxygen atoms among three different types of oxygen atoms present in CA-two in the
      acetate group and one in the ether linkage. Upon incorporation of AgBF4 into CA,
      the carbonyl stretching frequency of the free cellulose acetate at 1750 cm(-1)
      shifts to a lower frequency by about 41 cm(-1). The binding energy corresponding
      to a carbonyl oxygen atom in the O 1s XPS spectrum shifts to a more positive
      binding energy by the incorporation of AgBF4. Reversible olefin coordination to
      silver ions has been observed by FT-IR and UV studies. Treatment of the AgBF4-CA
      membrane placed in a gas cell with propylene produces a propylene-coordinated
      membrane in which coordinated propylene is easily replaced by other olefins such
      as 1,3-butadiene.

PMID- 11330909
TI  - Time-resolved spectroscopy of sulfur- and carboxy-substituted N
      alkylphthalimides.
AB  - The photophysical and photochemical properties of N-phthaloyl-methionine (1), S
      methyl-N-phthaloyl-cysteine methyl ester (2) and N-phthaloyltranexamic acid (3)
      were studied by time-resolved UV/Vis spectroscopy, using laser pulses at 248 or
      308 nm. The quantum yield of fluorescence is low (phi(f)< 10(-2)) for 1-3 in
      fluid and glassy media, whereas that of phosphorescence is large (0.3-0.5) in
      ethanol at - 196 degrees C. The triplet properties were examined in several
      solvents, at room temperature and below. The spectra and decay kinetics are
      similar, but the population of the pi(pi*) triplet state, as measured by T-T
      absorption, is much lower for 1 and 2 than for 3 or N-methyltrimellitimide (5')
      at ambient temperatures. The quantum yield (phi(delta)) of singlet molecular
      oxygen O2(1deltag) formation is substantial for 3 and 5' in several air- or
      oxygen-saturated solvents at room temperature, but small for 2 and 1. The quantum
      yield of decomposition is substantial (0.2-0.5) for 3 and small (<0.05) for 2 and
      1. It is postulated that photoinduced charge separation in the spectroscopically
      undetectable 3n,pi* state may account for the cyclization products of 1 and 2. In
      aqueous solution, this also applies for 3, whereas in organic solvents
      cyclization involves mainly the lower lying 3pi,(pi*) state. Triplet acetone,
      acetophenone and xanthone are quenched by 1-3 in acetonitrile; the rate constant
      is close to the diffusion-controlled limit, but smaller for benzophenone. While
      the energy transfer from the triplet ketone occurs for 3, a major contribution of
      electron transfer to the N-phthalimide derivative is suggested for 1 and 2, where
      the radical anion of benzophenone or 4-carboxybenzophenone is observed in
      alkaline aqueous solution.

PMID- 11330910
TI  - SiCNN--a new stable isomer with Si(triple bond)C triple bonding.
AB  - To predict potentially stable molecules with Si(triple bond)C triple bonding,
      theoretical calculations at the B3LYP/ 6-311G(d) and CCSD(T)/6-311G(2df) (single
      point) levels were employed to study the structures, energetics, and
      isomerization of various SiCN2 isomers. A schematic potential energy surface
      (PES) of SiCN2 was established to discuss the kinetic stability of the isomers. A
      new isomer SiCNN was found to possess a typical Si(triple bond)C triple bond, as
      confirmed by comparative calculations at the B3LYP, QCISD, QCISD(T), CCSD, and
      CCSD(T) levels on the bond lengths of SiCNN and other experimentally or
      theoretically known species of RSiCH (R = H, F, Cl, OH). Moreover, SiCNN resides
      in a very deep potential, the stabilization barrier is at least 53.2 kcal mol(
      1). Thus, SiCNN may be considered as the most kinetically stable isomer with
      Si(triple bond)C triple bonding known to date, and it may represent a very
      promising molecule for future experimental characterization. In addition, the
      stability of the other isomers, such as the four linear species SiNCN, SiNNC,
      NSiCN and NSiNC, a three-membered NNC ring isomer with exocyclic C-Si bonding,
      and a four-membered SiCNN ring isomer is discussed and compared with SiCNN.

PMID- 11330911
TI  - Phosphacarborane chemistry: the 7,8,9,11-, 7,9,8,10- and 7,8,9,10-isomers of nido
      P2C2B7H9--diphosphadicarbaborane analogues of 7,8,9,10-C4B7H11.
AB  - The reaction between the carborane arachno-4,6-C2B7H13 (1) and PCl3 in
      dichloromethane in the presence of a "proton sponge" (PS = 1,8
      dimethylaminonaphthalene) resulted in the isolation of the eleven-vertex nido
      diphosphadicarbaboranes 7,8,9,11-P2C2B7H, (2) and 3-Cl-7,8,11-P2C2B7H, (3-Cl-2)
      in yields of 54 and 7%, respectively. Replacement of the PS by NEt3 in the same
      reaction gave diphosphadicarbaboranes 2 and 3-CI-2 together with the isomeric
      species nido-7,9,8,10-P2C2B7H, (3) in yields of 28, 15 and 3%, respectively. The
      reaction between the isomeric carborane arachno-4,5-C2B7H13 (4) and PCl3 in
      dichloromethane in the presence of PS gave the asymmetrical isomer, nido-7,8,9,10
      P2C2B7H, (5). along with the chloro derivatives 4-Cl-7,8,9,10-P2C2B7H8 (4-Cl-5)
      and 11-Cl-7,8,9,10-PC2B7,H8 (11-Cl-5) (yields of 21, 1 and 13%, respectively).
      The structures of the chlorinated derivatives 3-Cl2 and 11 -Cl-5 were determined
      by X-ray diffraction analysis. In addition, the structures of all compounds
      isolated were geometry-optimised and confirmed by comparison of experimental 11B
      chemical shifts with those calculated by the GIAO-SCF/II//RMP2(fc)/6-31G* method.
      The calculations also include the structure and 11B NMR shifts of the isomer nido
      7,10,8,9-P2C2B7H9 (6) which has not yet been isolated.

PMID- 11330912
TI  - Selective adsorption of biopolymers on zeolites.
AB  - Zeolites adsorb biopolymers on their surface and may be suitable as a new type of
      chromatographic carrier material for proteins, nucleic acids, and their
      conjugates. We report here various parameters that influence the adsorption of
      biopolymers on synthesized zeolites with regard to the Si/Al2 ratio and three
      dimensional structure. There are three physicochemical principles that may
      underly the adsorption: 1) below the isoelectric point (pI), mainly Coulombic
      attraction similar to ion-exchange chromatography; 2) at pI, hydrophobic
      interactions (a kind of van der Waals attraction) plus the three-dimensional
      mesopore structure; and 3) above pI, the sum of the Coulombic repulsion and
      attraction forces, such as the hydrophobic interaction, and also substitution
      reaction of water on the Al molecule with a protein amino-base. At high Si/Al2
      ratio in the presence of a small amount of Al and with mesopores between the
      zeolite particles, maximal adsorption was seen at pI and was suggested to be
      dependent on the number of hydrophobic interaction points on the mesopores, and
      their morphology. The application of zeolites to biochemistry and biotechnology
      is also discussed.

PMID- 11330913
TI  - Synthesis of deuterium-labeled cryptophane-A and investigation of Xe@cryptophane
      complexation dynamics by 1D-EXSY-NMR experiments.
AB  - We present the synthesis of a series of deuterated cryptophanes 2-6 by a slightly
      modified procedure used for cryptophane-A. We show that for [Xe@cryptophane]
      complexes the use of variable-temperature one-dimensional 129Xe magnetization
      transfer (1D-EX-SY) allows the measurement of exchange rates. From these data the
      decomplexation activation energy Ea has been estimated to be 37.5+/-2 kJ mol(-1).
      The decomplexation activation enthalpy, deltaH(++) = 35.5+/-2 kJ mol(-1), and
      entropy, deltaS(++) = -60+/-5 J mol(-1) K(-1), have also been calculated. The
      calculated negative activation entropy suggests that the activated complex
      associated with decomplexation is conformationally more strained than the complex
      in its ground state.

PMID- 11330914
TI  - Hearing assessment of classical orchestral musicians.
AB  - Pure-tone audiometry was performed on 140 classical orchestral musicians employed
      at the Gothenburg Symphony Orchestra and the Gothenburg Opera in Sweden. This
      report is based on the results from hearing threshold measurements, presented as
      median audiograms according to gender, age group and instrument group. The
      results did not show severe hearing losses that could be attributed to exposure
      to musical noise. However, the study reflects the subjects' present hearing
      ability status and does not give an answer to the question of future hearing
      dysfunction. Female musicians were shown to have significantly better hearing
      thresholds in the high-frequency area than did male musicians. Furthermore, the
      median pure-tone hearing thresholds for the male musicians displayed a notch
      configuration at 6 kHz in the left ear, similar that of to noise-induced hearing
      loss. A small, but in general not significant, difference was detected when
      comparing the median hearing thresholds between each instrument group. Percussion
      and woodwind players displayed slightly worse hearing thresholds than did other
      musicians. Players of large string instruments had the best hearing threshold
      values. When comparing age groups and gender it was noted that the median hearing
      thresholds were stable and within 20 dB HL up to the age group of 40-49 years for
      both females and males.

PMID- 11330915
TI  - The change in the acoustic admittance phase angle: a study in children suffering
      from acute otitis media.
AB  - Middle ear mechanics, in normal and in pathological conditions, is the subject of
      this research, with acoustic impedance measurements as the cornerstone. Previous
      studies have established the importance of admittance-phase tympanograms, mainly
      in frequencies higher than the conventional 226 Hz. The purpose of the present
      study was to record how acute otitis media (AOM) affects the middle ear system
      and function by evaluating the recordings of the change in phase angle parameter
      (deltatheta) provided by an automated tympanometer using the sweep-frequency
      technique. Multifrequency and conventional tympanograms were obtained from 70
      children suffering from AOM on consecutive visits. Values of deltatheta from
      these subjects were compared to normative data previously acquired in our
      Department. It appears that changes in the mechanical status of the middle ear
      after AOM are reflected in abnormal deltatheta values, despite the normal
      findings of conventional tympanometry. A positive history of AOM did not seem to
      influence the behaviour of the middle ear. In most cases, abnormal deltatheta
      values coexisted with abnormal values of resonance frequency (RF), i.e. the
      frequency at which mass and stiffness of the middle ear are in balance, and total
      susceptance (deltaB) reaches 0mmhos and the converse. The deltatheta seems to be
      an important indicator of middle ear mechanical status that can record changes
      occurring in the system after AOM and undetected by low probe-tone tympanometry.

PMID- 11330916
TI  - The importance of pre-analysis windowing on auditory brainstem response fast
      Fourier transform analysis.
AB  - Analysis of auditory brainstem response (ABR) frequency content using fast
      Fourier transform (FFT) analysis has been used to improve ABR sensitivity and
      specificity as a diagnostic/site of lesion assessment tool, to improve our
      understanding of ABR components, and to guide ABR stimulus and recording
      parameter settings. Threatening this success, however, is the literature's poor
      control of pre-FFT windowing of the ABR prior to ABR FFT analysis. This study
      examined the significance of using no (NW), vs Blackman (BW), vs modified
      Blackman (MBW) pre-FFT windows on the FFT analysis of ABRs recorded from normal
      subjects. Pre-FFT windowing was shown to significantly reduce (p < 0.00005) ABR
      FFT magnitudes, but not frequencies, with BW causing greater reductions than MBW.
      The high significance of these results shows that choice of pre-FFT window is
      critical in any ABR FFT analysis.

PMID- 11330917
TI  - Speech-evoked cortical potentials and speech recognition in cochlear implant
      users.
AB  - Processing in the auditory cortex may play a role in the unexplained variability
      in cochlear implant benefit. P300 and N1/P2 were elicited in post-lingually deaf
      cochlear implant users wearing a Nucleus multichannel cochlear implant. Four
      sound contrasts were presented (500-1,000 Hz, /ba/-/da/, /ba/-/pa/ and /i/-/a/).
      N1 and P2 were present in all subjects for all conditions. Prolonged N1, P2 and
      P300 latencies were found in the cochlear implant group compared to a control
      group of subjects with normal hearing. Cochlear implant users show smaller
      amplitudes of N1 for all the speech signals as well as smaller amplitudes of P2
      for the consonants compared to the controls. P300 results of the cochlear implant
      users were compared to behavioural results of speech recognition testing. A
      relation was found between P300 amplitude and magnitude for the 500-1,000 Hz and
      /i/-/a/ contrasts and behavioural speech recognition in cochlear implant users.
      The results suggest that P300 measurements are useful and have additional value
      to speech recognition evaluations in cochlear implant users.

PMID- 11330918
TI  - Thresholds determined using the monotic and dichotic multiple auditory steady
      state response technique in normal-hearing subjects.
AB  - Auditory steady-state responses (ASSRs) were elicited by presenting single or
      multiple, 77-105 Hz amplitude-modulated 0.5, 1, 2, and 4 kHz tones to one or both
      ears. Objectives of this study were to (i) replicate and extend previous multiple
      ASSR studies in a quiet double-walled sound booth, and (ii) discover differences
      (if any) between thresholds assessed in monotic and dichotic conditions, which
      ranged between 15 and 22dB SPL. The present study's behavioural and ASSR
      thresholds are 0-10 dB lower (better) than results of previous monotic studies.
      Further, there are no significant differences in ASSR thresholds between dichotic
      and monotic stimulus conditions. Therefore, dichotic multiple AM tone stimulation
      does not produce a change in the ASSR that affects threshold estimation in a
      clinically significant manner. Thus, at least for detecting normal hearing, the
      dichotic multiple ASSR technique is a feasible method for estimating hearing
      thresholds that would substantially reduce recording time compared to
      conventional single-stimulus techniques.

PMID- 11330919
TI  - The I' potential of the human auditory brainstem response to paired click
      stimuli.
AB  - When stimulated with an appropriate stimulus, the hair cells of the organ of
      Corti depolarize, causing the release of a neurotransmitter substance, which
      excites afferent VIIIth nerve dendrites. It is reasonable to hypothesize that
      excitatory postsynaptic potentials (EPSPs) generated by the dendrites of the
      auditory nerve in turn initiate a compound action potential (CAP). The EPSP is
      thought to be the generator potential for the CAP, and may be recorded in
      auditory brainstem responses (ABRs) as the I' potential. Determining the
      anatomical origin of I' may enhance the sensitivity of the ABR technique in hair
      cell/dendrite/auditory nerve evaluations. Whether I' is of sensory or of neural
      origin is equivocal, and therefore I' is not well understood. To investigate this
      dilemma, ABRs were recorded from human subjects using standard and paired-click
      stimuli, and using subtraction methods to generate a derived ABR. Two early
      peaks, designated as I degree and I', occurred before wave I in the derived ABR.
      It was hypothesized that peaks I degrees and I' represent the summating potential
      and the generator potential, generated by the cochlea and VIIIth nerve dendrites,
      respectively.

PMID- 11330920
TI  - Referrals to a hospital-based child abuse committee: a comparison of the 1960s
      and 1990s.
AB  - OBJECTIVE: Although reports of child maltreatment have increased yearly since
      national data were first collected in 1976, little information is available about
      changes in the characteristics of children reported. Therefore, to examine
      changes over time in recognition and reporting in a medical setting, we compared
      referrals to a hospital-based child abuse committee in the late 1960s and early
      1990s. DESIGN: Retrospective, cross-sectional review of medical records and logs
      of the hospital's child abuse committee. SETTINGS: Ambulatory, emergency, and
      inpatient services at Yale-New Haven Hospital. PATIENTS: Medical records were
      reviewed for 101 of the 165 children referred to the child abuse committee in
      1968-1969 (early group) and 107 of the 843 children referred in 1990-1991 (late
      group). Cases of sexual abuse were excluded. RESULTS: Referrals for nonsexual
      abuse cases increased from 80 children per year in the early group to 181.5 per
      year in the late group; the late group was characterized by a larger number of
      newborn referrals (1% vs. 52%, p < .001). When non-newborns were compared, the
      two groups were similar with respect to gender and race, but the late group had
      fewer patients with private insurance (31% vs. 12%, p < .05). The late group also
      had more female-headed households (32% vs. 67%, p < .05) and more parents with a
      history of substance abuse (4% vs. 49%, p < .001). Excluding newborns, who were
      all classified as "at-risk," the types of problems were classified as abuse (41%
      early vs. 29% late), neglect (41% vs. 35%), and "at-risk" (16% vs. 35%). Although
      the types of injuries were similar: superficial injuries (20% vs. 16%), burns (9%
      vs. 8%), and fractures (6% vs. 4%), fewer maltreated children suffered physical
      injuries in the late group (71% vs. 49%, p < .05). CONCLUSIONS: A substantial
      change has occurred in referrals to the hospital's child abuse committee for
      abuse or neglect. Most referrals have become socially high-risk newborns and
      children or children with minimal injuries. This shift is likely due to broader
      definitions of maltreatment and earlier recognition of troubled families.

PMID- 11330921
TI  - The path to adoption for children of color.
AB  - OBJECTIVE: This article focuses on the path to adoption for children involved in
      the public child welfare system. METHOD: Descriptive and event history analyses
      were conducted of 1,550 children who had been removed from their homes and placed
      in out of home care in the child welfare system in Kansas and have adoption as a
      goal. RESULTS: African American children consistently took longer to reach
      significant milestones, including adoption placement and finalization.
      CONCLUSION: African American children are over-represented throughout the
      progression from substantiated abuse to adoption. Future research in other states
      should focus on whether this trend is unique to Kansas or applicable in other
      states. Additionally, efforts should be devoted to investigating the social,
      psychological, cultural, and systemic factors contributing to this differential
      treatment. Finally, there is a dire need to develop and evaluate interventions
      targeted at meeting the specialized needs of African American children in this
      system.

PMID- 11330922
TI  - Reducing risk for children in changing cultural contexts: recommendations for
      intervention and training.
AB  - OBJECTIVES: This paper proposes guidelines to both parents and professionals for
      the prevention and reduction of risk associated with cultural differences,
      conflicts and misinterpretations. These guidelines are based on a conceptual
      framework derived from the multicultural reality of Israeli society and are
      supported by a growing corpus of studies on cross-cultural child development,
      immigration and minority families. METHOD: The paper is based on a conceptual
      model followed by practical implications for training and intervention. RESULTS:
      Central to this paper is the concept of the "adaptive adult" which serves as a
      guiding metaphor for the organization of socialization goals, child-rearing
      ideologies, perceptions and values of socializing agents in a given culture or
      group. Childcare practices are defined as adaptive strategies, that is, means for
      socializing children to become "successful adults." The paper describes different
      types of "adaptive adult" metaphor (e.g., past and future oriented), and
      discusses images held by groups who have experienced either a duality of private
      and public culture or changes in their cultural contexts. The paper further
      explores and exemplifies the potential contributions of the proposed framework
      for a five step intervention plan with parents and for training of professionals
      in multicultural contexts. CONCLUSIONS: Children of families in changing cultural
      contexts are often considered to be at risk for maltreatment. This is because
      such families may experience sociocultural and socioeconomic change and a loss of
      their former support networks. Parental acculturation stress and related
      dysfunction might also affect children. The risk increases when children are
      exposed to systems with conflicting socialization goals and with contradictory
      definitions of desirable child-care or supervision frameworks. Conflicts and
      clashes between parents and socializing agents have been found to have long-term
      detrimental effects on children and families. Cultural differences may also
      result in misinterpretation of parental behaviors and misdiagnosis of abuse and
      neglect. Such conflicts and misinterpretations can be avoided if both parents and
      social agents learn to understand and to respect their cultural differences, so
      that together, they can devise ways to bridge them.

PMID- 11330923
TI  - The behavioral and emotional problems of former unaccompanied refugee children 3
      4 years after their return to Vietnam.
AB  - OBJECTIVE: The objective of this study was to examine the behavioral and
      emotional problems of former unaccompanied refugee children who had repatriated
      to Vietnam from refugee centers in Hong Kong and South East Asia. The children
      were compared with a matched sample of children who had never left Vietnam.
      METHOD: The participants consisted of 455 Vietnamese children aged between 10 and
      22 years; 238 of the children had formerly resided in refugee camps without their
      parents. Data were collected using the Achenbach Youth Self-Report, the Cowen
      Perceived Self-Efficacy scale, a Social Support scale as well as an Exposure to
      Trauma scale. RESULTS: No significant difference was found between the two groups
      of children on the YSR Total Score. The former refugee children had significantly
      lower Externalizing scores and failed marginally to report significantly higher
      Internalizing scores than the local children. The study showed that the perceived
      self-efficacy, number of social supports and experience of social support did not
      differ between the two groups of children. Further analysis showed that a
      significant interaction between the immigration status of the children and the
      children's subjective perception of their current standard of living explained
      the differences in the YSR. CONCLUSION: The results suggest that the experience
      of living without parents in a refugee camp does not lead to increased behavioral
      and emotional problems in the immediate years after repatriation.

PMID- 11330924
TI  - Epidemiology and etiology of reported cases of child physical abuse in Zimbabwean
      primary schools.
AB  - OBJECTIVE: There were two objectives: First, to determine the nature and extent
      of physical abuse perpetrated on primary school pupils by their teachers; second,
      to determine why some teachers physically abuse their primary school pupils in
      Zimbabwe. METHOD: Epidemiological data of reported physical abuse by teachers in
      Zimbabwe between January 1990 and December 1997 were analyzed using information
      in their files. RESULTS: The study found that 78.9% of the perpetrators were male
      while 21.1% were female; 92.1% of the perpetrators were trained teachers while
      7.9% were untrained; 58.7% of the victims were male while 41.3% were female;
      91.4% of the cases were reported by the pupils themselves and 8.7% by the school
      head; 73.9% of these cases were reported to the Ministry of Education and 26.1%
      to the police. In this study, 80.4% of the victims were beaten, whipped or hit by
      their perpetrators; 10.9% were clapped or slapped; 4.3% were punched with fists;
      2.2% each were kicked and pinched, respectively. CONCLUSIONS: The findings
      indicate that teachers perpetuate various forms of physical abuse and that this
      form of abuse is now on the increase. The findings indicate that some
      perpetrators use corporal punishment on female pupils against the stipulated
      Public Service (Disciplinary) Regulations. What is clear is that the Public
      Service (Disciplinary) Regulations seem not to be deterrent enough because the
      majority of the perpetrators are merely fined or reprimanded while only a very
      small percentage is discharged from the teaching service.

PMID- 11330925
TI  - Child abuse in Turkey: an experience in overcoming denial and a description of 50
      cases.
AB  - OBJECTIVE: To share the experiences of the first clinical multidisciplinary child
      abuse and neglect (CAN) team in Turkey with international child abuse community.
      METHODS: The authors established the first Turkish CAN follow-up team at Dr.
      Behcet Uz Children's Hospital. Following a training program in five teaching
      hospitals in Izmir, the authors kept a record of every case diagnosed with CAN
      from these hospitals between 1996 and 1998. The demographic, epidemiologic, and
      medical features of this case series are summarized. RESULTS: Fifty cases were
      diagnosed and followed-up. Seventy-six percent of patients were reported from Dr.
      Behcet Uz Children's Hospital. Age and sex distribution was 9.2 +/- 6.7 years and
      46% male, 54% female, respectively. The offenders were only father in 38%, only
      mother in 28%, and multiple in 34%. More than three CAN risk factors were present
      in 94%. Of the children reported 44% survived, 14% died, and 42% were lost to
      follow-up. Sixteen percent were free of reabuse, and 42% survived with handicaps.
      CONCLUSIONS: Child abuse and neglect is a reality in Turkey. The team's work
      increased pediatricians' awareness of CAN. Reporting these cases to Social
      Affairs Bureau was established for the first time in Turkey. Physicians in Turkey
      need training to diagnose and properly report CAN. The implemen tation of a
      national CAN prevention program is an urgent need for Turkey.

PMID- 11330926
TI  - Sexual victimization and adolescent weight regulation practices: a test across
      three community based samples.
AB  - OBJECTIVE: This study had four objectives: 1) to examine the association between
      sexual victimization and weight regulation across three samples of adolescent
      girls, 2) to assess whether sexual victimization is associated with more extreme
      forms of weight regulation in girls, 3) to discern whether sexual victimization
      has implications for the use of multiple forms of weight regulation, and 4) to
      address the role of physical victimization in explaining these relationships.
      METHOD: Data from three separate samples of 9th-12th graders were used to test
      these hypotheses. Girls from the upper Midwest responded to survey questions
      related to victimization and weight regulation in a largely urban sample (N =
      2,086), a rural sample (N = 2,629), and a statewide sample (N = 966). RESULTS:
      Logistic regression revealed that sexual victimization was consistently
      associated with weight regulation in adolescent girls, independent of the effects
      of physical victimization. In the urban sample, being sexually victimized was
      associated with an increase in the probability of purging by 18% relative to not
      being sexually victimized. Sexual victimization was associated more strongly with
      extreme forms of weight regulation and significantly discriminated whether girls
      would choose multiple weight regulation forms. CONCLUSIONS: Sexual victimization
      contributes unique variance to the probability that girls will practice weight
      regulation techniques. Data from three independent samples confirms that being
      violated sexually places girls at risk for various health compromising eating
      behaviors.

PMID- 11330927
TI  - Bias assessment for child abuse survey: factors affecting probability of response
      to a survey about childhood abuse.

PMID- 11330928
TI  - Clinical performance of a laser fluorescence device for detection of occlusal
      caries lesions.
AB  - Children and adolescents must be examined often for occlusal caries. Diagnosis of
      fissure caries is difficult especially when the tooth surface appears seemingly
      intact. It has been shown that using traditional clinical methods, as little as
      20% of teeth with fissure caries under intact surfaces were correctly recognised
      as such. Therefore, new methods for increasing the accuracy of diagnosis have
      been sought for years. Recently, a new device, based on fluorescence
      measurements, was introduced. The purpose of this study was to test the device
      under in vivo conditions in order to provide recommendations for its use in the
      dental office. Seven general dental practitioners examined a total of 332
      occlusal surfaces in 240 patients. Caries extent was determined for each site
      after operative intervention (='gold standard'). Clinical inspection and analysis
      of bitewing radiographs exhibited statistically significant lower sensitivities
      (31-63%) than did the DIAGNOdent device (sensitivity > or = 92%). It is
      recommended that the laser device is used in the decision-making process in
      relation to the diagnosis of occlusal caries as a second opinion in cases of
      doubt after visual inspection.

PMID- 11330929
TI  - Is the observed association between periodontitis and atherosclerosis causal?
AB  - Most of the documentation of possible causal links between periodontitis and
      atherosclerosis-related diseases appears indirect or circumstantial. There is,
      however, an increasing number of both experimental and longitudinal
      epidemiological studies which seem to support a causal relationship. A critical
      evaluation of the epidemiological data available might therefore be appropriate.
      The present study is based on a literature search using Ovid medical data base
      covering the period from 1989 to October 2000 and applying specific inclusion
      criteria. Based on a critical evaluation of the 14 investigations selected from a
      total of 21 retrieved from the search, a causal relationship between
      periodontitis and atherosclerosis-related diseases appeared possible. However,
      the nature both of periodontitis and atherosclerosis is multifactorial, and
      caution should be exercised when implicating periodontal disease in the causation
      of atherosclerotic disorders.

PMID- 11330930
TI  - Longitudinal study of dental caries, tooth mortality and interproximal bone loss
      in adults with intellectual disability.
AB  - The investigation focused on longitudinal changes of oral health in a group of
      adults with intellectual disability. A number of 124 individuals, aged 21-40 yr
      in 1990, were followed during 8.5 yr. The incidence and prevalence of caries,
      incidence of tooth mortality, and interproximal bone loss were registered from
      clinical examinations and bite-wing radiographs. The subjects visited the dental
      clinic for preventive dental care on average every third month during the period.
      The caries incidence was low, on average 0.51 new lesions per yr. Persons with
      mild intellectual disability experienced more caries than other subjects. During
      the 8.5 yr, the subjects had lost on average 1.82 teeth, with periodontitis
      dominating as the reason for tooth mortality. Individuals who cooperated poorly
      with dental treatment had lost the most teeth. The average annual bone loss in
      all subjects was 0.03 mm. Subjects with Down syndrome had a higher bone loss
      compared to those with other diagnoses of intellectual disability. Thus, the
      major part of the persons with intellectual disability showed satisfactory oral
      health. However, subjects with poor ability to cooperate with dental treatment
      and subjects with Down syndrome showed an increased risk for impaired oral
      health.

PMID- 11330931
TI  - Dental anxiety in relation to mental health and personality factors. A
      longitudinal study of middle-aged and elderly women.
AB  - Little is known about the longitudinal course of dental anxiety in relation to
      age, mental health and personality factors. In 1968 69 a representative sample of
      778 women aged 38 to 54 yr took part in a psychiatric examination. Three hundred
      and ten were followed up in 1992-93. A phobia questionnaire, including assessment
      of dental fear, and the Eysenck Personality Inventory were distributed to the
      participants at both occasions. High dental fear was reported by 16.8% of the
      women at baseline and was associated with a higher number of other phobias, a
      higher level of neuroticism, more psychiatric impairment, more social disability
      due to phobic disorder, and a higher anxiety level. Among women who reported high
      dental fear in 1968 69 (n=36), 64% remitted and 36% remained fearful. Among women
      with low dental fear in 1968 69 (n = 274), 5% reported high dental fear in 1992
      93. Chronicity was associated with higher neuroticism, lower extraversion, and
      more psychiatric impairment at base-line. Remission was associated with higher
      extraversion at baseline. Dental anxiety increased or decreased over time in
      concert with the number of other fears.

PMID- 11330933
TI  - Influence of periodontal receptors on the jaw-jerk reflex amplitude in man.
AB  - To study the role of periodontal mechanoreceptors in the modulation of the human
      jaw-jerk reflex, 60 reflexes were elicited in each of six healthy individuals
      under three different conditions: (a) with unilateral tooth support on the
      ipsilateral side; (b) with support on the contralateral side; and (c) with
      support and local anesthesia of the periodontal tissues on the ipsilateral side.
      During all conditions, background muscle activity and mandibular displacement
      were kept as constant as possible. Using on-surface EMG and the amplitude of the
      first peak of the biphasic jaw-jerk potential as the outcome variable, a
      condition-dependent reflex amplitude was found for the visually controlled right
      anterior temporalis muscle. Specifically, the 'ipsilateral support plus
      anesthesia' condition yielded higher amplitudes than the 'ipsilateral support'
      condition. Highest amplitudes were found for the 'contralateral support'
      condition. It was concluded that periodontal mechanoreceptors on the ipsilateral
      side have an inhibitory effect on the jaw-jerk reflex amplitude in the anterior
      temporalis muscle.

PMID- 11330932
TI  - Periodontal infections and pre-term birth: early findings from a cohort of young
      minority women in New York.
AB  - The aim of this report is to provide early data from an ongoing study examining
      (i) the relationship between periodontal infections and pre-term low birth weight
      (PLBW) in a cohort of young, minority, pregnant and post-partum women; and (ii)
      the effect of periodontal interventions on pregnancy outcome. During the first 2
      yr of the study, 213 women were enrolled and examined clinically for dental
      plaque, calculus, bleeding on probing, and probing depth. Birth outcome data were
      available for 164 women, including one group (n = 74) subjected to oral
      prophylaxis during pregnancy, and a second group (n=90) who received no prenatal
      periodontal treatment. Subgingival plaque samples were available from 145
      subjects (4 samples/subject) and were analyzed by checkerboard DNA hybridization
      with respect to 12 bacterial species. The prevalence of PLBW was 16.5% (27 cases)
      in this cohort. No differences in clinical periodontal status were observed
      between PLBW cases and women with normal birth outcome. However, PLBW mothers had
      significantly higher levels of Bacteroides forsythus and Campylobacter rectus,
      and consistently elevated counts for the other species examined. PLBW occurred in
      18.9% of the women who did not receive periodontal intervention (17 cases), and
      in 13.5% (10 cases) of those who received such therapy.

PMID- 11330934
TI  - Production of Rantes/CCL5 in human gingival fibroblasts challenged with tumor
      necrosis factor alpha.
AB  - Chemokines are small-secreted proteins that stimulate the directional migration
      of leukocytes and thereby mediate the inflammatory process. The present study
      investigates the capacity of human gingival fibroblasts to produce the beta
      chemokine Rantes/CCL5. In situ hybridization, immunohistochemistry and ELISA were
      used to measure the induction of Rantes/CCL5 at the mRNA and protein levels, both
      in unstimulated gingival fibroblasts as well as in fibroblasts treated with the
      proinflammatory cytokines tumor necrosis factor (TNF)alpha or interleukin (IL)
      1beta. TNFalpha in different concentrations (0.1-10 ng/ml) induced Rantes/CCL5
      mRNA expression and protein production in 24-h cultures of human gingival
      fibroblasts. The expression of Rantes/CCL5-mRNA and protein production, induced
      by TNFalpha, was evident at 6 h and thereafter increased continuously during the
      study period (24 h). IL-1beta (3-300 pg/ml) also enhanced the production of
      Rantes/CCL5 in gingival fibroblasts. The amount of Rantes/CCL5 induced by IL
      1beta (300 pg/ml), however, was less than that induced by TNFalpha (10 ng/ml).
      The study suggests that human gingival fibroblasts, by producing the chemokine
      Rantes/CCL5, participate in the regulation of the host response during the
      inflammatory process in the periodontal tissue.

PMID- 11330935
TI  - Role of interleukin-1 in induction of matrix metalloproteinases synthesized by
      rat temporomandibular joint chondrocytes and disc cells.
AB  - To identify cartilage-degrading enzymes and cell types that can be specifically
      induced by interleukin-1 (IL-1)alpha, we studied matrix metalloproteinase (MMP)
      activities of cultured rat temporomandibular joint (TMJ) chondrocytes and disc
      cells. The cells were isolated from TMJs pre-injected with normal physiological
      saline (CR) or recombinant human IL-1alpha (AR). MMP activities in the
      conditioned media were assayed by gelatin enzymography, and they were identified
      by Western blot analyses. MMP mRNAs in these cells were also detected by RT-PCR.
      IL-1alpha significantly induced an increase of active MMP9 as well as pro- and
      active MMP3, but had no effect on the MMP2 activity in both types of cells. MMP3
      and MMP9 mRNAs were also inducible in these cells by IL-1alpha stimulation.
      Furthermore, disc cells were more susceptible to IL-1alpha than chondrocytes. AR
      cells spontaneously produced the same MMPs in vitro as the CR cells synthesized
      under IL-1alpha stimulation. The results indicate that MMP9 and MMP3 were
      predominantly produced by disc cells, and these may be considered to play a
      pivotal role in ECM degradation during pathological conditions of the TMJ, such
      as IL-1-induced TMJ arthritis.

PMID- 11330936
TI  - Electron-microscopic demonstration of proline-rich proteins, statherin, and
      histatins in acquired enamel pellicles in vitro.
AB  - Proline-rich proteins (PRPs), histatins, and statherin are salivary proteins that
      exhibit high affinities for hydroxyapatite surfaces. In vitro experiments with
      parotid submandibular/sublingual or whole saliva have shown these proteins to
      adsorb selectively to tooth surfaces. This investigation focuses on the histo
      morphological identification of PRPs, histatins, and statherin in acquired enamel
      pellicles. Synthetic hydroxyapatite or bovine enamel were exposed to glandular
      secretions, and whole saliva and pellicle precursor proteins were identified
      immunohistologically by electron microscopy. Results obtained by back-scattered
      scanning electron microscopy showed these proteins to be present in pellicles.
      Pellicles displayed a distinct structure consisting of a sponge-like meshwork of
      microglobules. Interconnections between structural elements were identified in
      submandibular/sublingual and whole saliva pellicles only. Transmission electron
      microscopy of pellicles formed on bovine enamel surfaces revealed a tendency for
      preferential localization of precursor proteins within the protein film. Since
      the data showed the presence of pellicle precursors in pellicles derived both
      from glandular secretions and from whole saliva, it is likely that PRPs,
      histatins, and statherin are integral components of acquired enamel pellicles in
      vivo.

PMID- 11330937
TI  - Human ameloblastin gene: genomic organization and mutation analysis in
      amelogenesis imperfecta patients.
AB  - A gene encoding the enamel protein ameloblastin (AMBN) was recently localized to
      a region on chromosome 4q21 containing a gene for the inherited enamel defect
      local hypoplastic amelogenesis imperfecta (AIH2). Ameloblastin protein is located
      at the Tomes processes of secretory ameloblasts and in the sheath space between
      rod-interrod enamel, and the AMBN gene therefore represents a viable candidate
      gene for local hypoplastic amelogenesis imperfecta (AI). In this study, the
      genomic organization of human AMBN was characterized. The gene was shown to
      consist of 13 exons and 12 introns. An alternatively spliced 45 bp sequence was
      shown not to represent a separate exon and is most likely spliced by the use of a
      cryptic splice site. The finding that there were no recombinations between an
      intragenic microsatellite and AIH2 encouraged us to evaluate this gene's
      potential role as a candidate gene for local hypoplastic AI. Mutation screening
      was performed on all 13 exons in 20 families and 8 sporadic cases with 6
      different forms of AI. DNA variants were found but none that was associated
      exclusively with local hypoplastic AI or any of the other variants of AI in the
      identified Swedish families. This study excludes the coding regions and the
      splice sites of AMBN from a causative role in the pathogenesis of AIH2.

PMID- 11330938
TI  - Radical hysterectomy: lessons in risk reduction.

PMID- 11330939
TI  - Changes in the demographics and perioperative care of stage IA(2)/IB(1) cervical
      cancer over the past 16 years.
AB  - OBJECTIVES: The aim of this study was to determine whether there have been any
      significant changes in the demographics and perioperative care of FIGO stage
      IA(2)/IB(1) cervical cancer over the past 16 years and, if so, to quantify them.
      METHODS: Since July 1984, all patients with FIGO stage IA(2)/IB(1) cervical
      cancer undergoing radical surgery by members of our division have been entered
      into a prospective database. Selection for surgery has been unchanged over the
      past 16 years. Since March 1994 and November 1996, one surgeon has performed
      radical vaginal trachelectomy and laparoscopic assisted radical vaginal
      hysterectomy, respectively. Statistical analysis used Spearman's correlation
      analysis, the proportional hazards regression model of Cox, and the Mantel-Hanzel
      test was performed. Due to the number of statistical analyses, statistical
      significance was defined as P < 0.01. RESULTS: Eight hundred sixty-four patients
      have undergone radical surgery (784 radical hysterectomy, 42 radical vaginal
      trachelectomy, 32 radical vaginal hysterectomy, 6 radical abdominal
      trachelectomy) for FIGO stage IA(2)/IB(1) carcinoma of the cervix by members of
      our division since 1984. There have been no changes in the median age (40 years),
      tumor size (2.0 cm), incidence of capillary lymphatic space involvement (47%), or
      positive pelvic lymph nodes (6%) over the past 16 years. The median Quetelet
      index (24.6), depth of tumor invasion (squamous cell carcinomas only) (6.0 mm),
      and proportion of patients with comorbid conditions (17%) have increased over
      time (P = 0.001, P = 0.003, and P < 0.001, respectively). Pathologically, there
      has been an increase in the proportion of adenocarcinomas (28%) and a decrease in
      the proportion of grade 3 tumors (28%) (P < 0.001 and P < 0.001, respectively).
      The median operating time (2.8 h), hospital stay (7.0 days), blood loss (600 cc),
      allogeneic blood transfusion (23%), postoperative infections (13%), and
      noninfectious complications (6%) have all decreased (P < 0.001, P < 0.001, P <
      0.001, P < 0.001, P < 0.001, and P = 0.002, respectively). There has been no
      change in the incidence of positive surgical margins (3%), adjuvant radiation
      (13%), or recurrence-free survival (2 and 5 years, 94 and 90%, respectively)
      after a median follow-up of 45 months. CONCLUSION: Despite no substantive changes
      in the selection criteria for surgery and the small time interval studied (16
      years), almost all indices of operative and postoperative morbidity analyzed have
      decreased significantly. These changes have occurred without an increase in the
      use of adjuvant radiation or decrease in recurrence-free survival. Although
      little progress has been made in the cure rates associated with surgical
      management of FIGO stage IA(2)/IB(1) cervical cancer during this time interval,
      it appears that the morbidity of surgery has decreased.

PMID- 11330940
TI  - Epitope recognition by anti-cathepsin D autoantibodies in endometrial cancer
      patients.
AB  - OBJECTIVE: This study analyzed a model for the identification of specific
      epitopes recognized by autologous tumor-reactive humoral responses of endometrial
      cancer patients as potential markers for the monitoring of cancer. METHODS: The
      presence of circulating pro- and mature forms of cathepsin D and antibodies
      reactive with this enzyme were identified by Western immunoblot and quantitated
      by an enzyme immunoassay. Specific immunoreactivities with 34- and 52-kDa
      cathepsin D forms were analyzed by Western immunoblot using sera from endometrial
      cancer patients (n = 40) and normal volunteers (n = 15). Subsequently,
      reactivities with specific cathepsin D epitopes were defined by a peptide
      specific ELISA. RESULTS: Circulating pro-forms of cathepsin D were detected in 31
      of 40 endometrial cancer patients tested and none of the control volunteers.
      Circulating IgG reactive with cathepsin D could be demonstrated in 29/31 patients
      with circulating procathepsin D, while an anti-cathepsin D response was not
      detectable in normal controls. This response appeared to be directed against the
      pro-peptide portion of cathepsin D. Using a peptide-specific ELISA, the
      frequencies of antibody production against specific epitopes within the pro
      peptide were defined. CONCLUSION: There is a demonstrable tumor-reactive immune
      response elicited in endometrial cancer patients, directed against specific
      antigenic epitopes, some of which are conserved among these patients. Since these
      proteins are recognized as non-self, due at least in part to posttranslational
      processing errors, defining these epitopes will be useful as a means of
      diagnosis, assessment of therapeutic success, and, ultimately, identification of
      immunotherapeutic targets.

PMID- 11330941
TI  - A vaginal and extraperitoneal approach to surgically stage patients with
      endometrial cancer.
AB  - OBJECTIVE: The purpose of this project was to prospectively evaluate the
      feasibility of an alternative technique for surgically staging patients with
      endometrial cancer. METHODS: Patients with endometrial cancer were enrolled in
      this protocol from September 1999 until August 2000. The staging procedure
      included pelvic washings via colpotomy, total vaginal hysterectomy, bilateral
      salpingo-oophorectomy (TVH/BSO), and extraperitoneal pelvic and paraaortic
      lymphadenectomy (EP-LND) if indicated. Tumor characteristics, time and
      feasibility of surgical procedures, length of hospital stays, and complications
      were prospectively recorded. RESULTS: Twenty-one patients were enrolled. Grade 1,
      2, and 3 tumors were identified in 6 (29%), 10 (48%), and 5 (24%) patients,
      respectively. Pelvic washings and TVH/BSOs were performed on all patients. A
      total of 21/21 (100%) uterine specimens were removed vaginally and 41/42 (98%)
      adnexa were resected vaginally. EP-LNDs were performed on 17 (81%) patients due
      to pathologic findings of the uterine specimens. The median time to perform a
      TVH/BSO was 68 (47-149) min. The median time to complete a EP-LND was 77 (59-107)
      min. The median number of postoperative days was 1 (1-5). Complications were
      infrequent and mild. CONCLUSIONS: TVH/BSO, pelvic washings, and EP-LND is a
      feasible alternative to standard surgical staging of endometrial cancer. The
      minimal amount of exposure to the intraperitoneal space makes this approach
      arguably the least invasive for endometrial cancer staging and accounts for the
      decrease in recovery time and shortened hospital stays. The acceptable length of
      surgical time, short hospital stays, and minimal requirements for surgical
      instruments make this approach potentially the most cost-effective option for
      surgically staging patients with endometrial cancer. A randomized trial comparing
      this technique to standard surgical staging is warranted.

PMID- 11330942
TI  - Analysis of treatment failures and survival of patients with fallopian tube
      carcinoma: a cooperation task force (CTF) study.
AB  - OBJECTIVE: The objective of this retrospective multicenter study was to assess
      the pattern of failures and survival of patients with primary carcinoma of the
      fallopian tube. METHODS: The hospital records of 88 patients with primary
      carcinoma of the fallopian tube were reviewed. Surgery was the initial therapy
      for all patients. Tumor stage was I in 21 (23.9%), II in 21 (23.9%), III in 43
      (48.8%), and IV in 3 (3.4%) patients. Postoperative treatment was given without
      well-defined protocols. The median follow-up of survivors was 55 months (range, 7
      182). RESULTS: Of the 21 patients with stage I disease, 10 had no postoperative
      treatment and 11 had platinum-based chemotherapy. Five (23.8%) patients recurred
      after a median of 29 months (range, 8-93) from initial surgery. Of the 21
      patients with stage II disease, 2 had no postoperative treatment, 2 underwent
      external pelvic irradiation, 16 received platinum-based chemotherapy, and 1
      patient had oral melphalan. Eight (38.1%) patients recurred after a median of
      25.5 months (range, 7-57). Of the 46 patients with stage III-IV disease, 1
      patient refused chemotherapy and died after 19 months and 45 patients received
      platinum-based chemotherapy. A clinical complete response was obtained in 29
      (64.4%) patients and a partial response in 8 (17.8%). A second-look laparotomy
      was performed in 14 of the 29 clinically complete responders: 12 patients were
      found to be in pathological complete response and 2 had persistent disease. Six
      (50.0%) of the former recurred after a median of 22 months (range, 13-101) from
      initial surgery. The two patients with persistent disease developed tumor
      progression after 15 and 11 months, respectively. Fifteen clinically complete
      responders did not undergo second-look, and 7 (46.7%) of them had a recurrence
      after a median of 18 months (range, 9-41). For the whole series, 5-year survival
      was 57%. By log-rank test, survival was related to FIGO stage (III-IV vs I-II, P
      = 0.0001), tumor grade (G3 vs G1 + G2, P = 0.0038), and patient age (>58.5 years
      vs <58.5 years, P = 0.0069), but not to histological type. The Cox model showed
      that FIGO stage (P = 0.0018) and patient age (P = 0.0290) were independent
      prognostic variables for survival. Among the patients with stage III-IV disease,
      5-year survival was 55% for the patients who had residual tumor <1 cm compared
      with 21% for those who had larger residuum (P = 0.0169). CONCLUSIONS: Primary
      carcinoma of the fallopian tube shares several biological and clinical features
      with ovarian carcinoma. However, when compared with the latter, fallopian tube
      carcinoma more often tends to recur in retroperitoneal nodes and distant sites.
      Stage, patient age, and, among patients with advanced disease, residual tumor
      after initial surgery represent important prognostic variables for survival.

PMID- 11330943
TI  - Prognostic parameters in endometrial stromal sarcoma: a clinicopathologic study
      in 31 patients.
AB  - OBJECTIVE: The aim of this study was to evaluate the behavior of endometrial
      stromal sarcomas (ESS) in relation to their clinical and pathologic features and
      to identify possible prognostic factors. METHODS: Thirty-one patients with
      histologically proven ESS were included in the analysis. Endometrial stromal
      sarcoma is characterized by proliferations composed of cells with endometrial
      stromal cell differentiation. A breakpoint of 10 mitoses per 10 high-power fields
      was used in the statistical analysis to distinguish between low-grade and high
      grade endometrial stromal sarcoma and to evaluate the prognostic value of mitotic
      count in patients with ESS. RESULTS: The median follow-up time was 72 months
      (range 34-110). The median overall survival of the 31 patients was 127 months,
      resulting in a 5-year overall survival rate of 62%. Adjuvant therapy was
      administered to 25 patients; among those, 20 patients received postoperative
      radiotherapy and 5 patients received chemotherapy. Ten of the irradiated patients
      and 3 patients undergoing chemotherapy developed disease recurrence. Concerning
      the response rate to adjuvant chemotherapy, 1 patient showed a complete response,
      1 patient a partial response, 1 patient stable disease, and 2 patients
      progressive disease. Altogether, 14 patients developed recurrent disease with a
      median disease-free survival of 11 months (range 5-60). Twelve patients died of
      the disease. A univariate model revealed that early tumor stage (P < 0.0007), low
      myometrial invasion (P < 0.008), and low mitotic count (P < 0.005) were
      associated with a lengthened overall survival in patients with endometrial
      stromal sarcoma. Age and adjuvant therapy did not influence overall survival of
      patients with ESS. CONCLUSION: Early tumor stage, low myometrial invasion, and
      low mitotic count are associated with a lengthened overall survival in patients
      with ESS.

PMID- 11330944
TI  - Caveolin-1 expression in advanced-stage ovarian carcinoma--a clinicopathologic
      study.
AB  - OBJECTIVE: The aim of this study was to analyze the correlation among the
      expression of caveolin-1, the protein constituent of caveolae, and disease
      outcome in advanced-stage ovarian carcinomas. METHODS: Sections from 76 primary
      ovarian carcinomas and metastatic lesions from 45 patients diagnosed with
      advanced-stage ovarian carcinoma (FIGO stages III-IV) were evaluated for caveolin
      1 expression using immunohistochemistry. Patients were divided into long-term
      survivors and short-term survivors based on disease outcome. Twenty nonneoplastic
      fallopian tubes and ovaries were additionally studied. RESULTS: The mean follow
      up period was 70 months. The mean values for disease-free survival and overall
      survival were 109 and 125 months for long-term survivors, compared to 3 and 21
      months for short-term survivors, respectively. Caveolin-1 expression was
      localized to the cell membrane in 24/76 (32%) specimens and was detected in the
      cytoplasm in 52/76 (68%) cases. Both patterns were more often detected in
      metastases, when compared with primary tumors. In addition, membrane
      immunoreactivity was more often seen in tumor of short-term survivors. These
      differences did not reach statistical significance (P > 0.05). Combined membrane
      and cytoplasmic immunoreactivity was seen in 17/20 (85%) nonneoplastic lesions.
      Despite its role in tyrosine-kinase-mediated signal transduction in vitro
      studies, caveolin-1 expression in carcinomas showed no association with the
      protein expression of c-erbB-2 and epidermal growth factor receptor, evaluated in
      a previous study of this patient cohort. CONCLUSIONS: This study provides the
      first in vivo evidence of caveolin-1 membrane expression in human malignancies.
      Caveolin-1 is often expressed in advanced-stage ovarian carcinoma, but does not
      appear to be a powerful predictor of disease outcome in these tumors. The reduced
      expression level in carcinomas compared to nonneoplastic epithelium may point to
      a role for caveolin-1 as a tumor suppressor gene.

PMID- 11330945
TI  - A novel amplification at 17q21-23 in ovarian cancer cell lines detected by
      comparative genomic hybridization.
AB  - OBJECTIVE: Little is known about the molecular mechanisms involved in the
      pathogenesis and/or progression of ovarian cancer (OC). To investigate the
      genomic imbalances and identify the cancer-related genes associated with this
      tumor, we applied comparative genomic hybridization (CGH) in OC cell lines.
      METHODS: Chromosomal aberrations among 17 OC cell lines were analyzed with CGH.
      Since novel chromosomal regions, including 17q21-23, were identified, we examined
      the involvement of two candidate genes, PS6K and ZNF147, mapped on this
      chromosomal region. We examined the status of amplification and expression by
      fluorescence in situ hybridization as well as by Southern blot analysis and by
      Northern blot analysis on two candidate genes, respectively. RESULTS: All lines
      displayed numerous chromosomal imbalances; the most frequent losses were observed
      on 18q22-23 (29.4%), 13q22-34 (23.5%), 9p (17.6%), 4p11-14 (17.6%), and 11p14-15
      (17.6%). The most common gains were noted at 20q12-13 (47.1%), 8q23-24 (35.2%),
      5p15 (23.5%), 7q32-36 (23.5%), and 20p (23.5%). High-level gains (HLGs) were
      detected at 20q12-13 (four cell lines), 8q24 (two cell lines), 12p11-12 (two cell
      lines), and 17q21-23 (two cell lines). PS6K and ZNF147 genes were amplified in
      two cell lines exhibiting HLGs at 17q21-23, but not overexpressed. CONCLUSIONS:
      Our CGH data indicate that OCs have various DNA copy number changes. Among these
      frequent changes, 17q21-23 may harbor another tumor-associated gene(s)
      responsible for OC carcinogenesis.

PMID- 11330946
TI  - Apoptosis and the expression of Bcl-2 and Bax in patients with endometrioid,
      clear cell, and serous carcinomas of the uterine endometrium.
AB  - OBJECTIVES: Clear cell and serous carcinoma of the uterus are rare types of
      endometrial carcinomas. This study was designed to investigate the differential
      occurrence of apoptosis, Bcl-2, and Bax in endometrioid, clear cell, and serous
      carcinomas. METHODS: In a total of 28 endometrial carcinomas as well as 4 samples
      of normal postmenopausal endometria, apoptotic changes were examined using
      molecular biochemical techniques. The expression of Bcl-2 and Bax proteins was
      also investigated by immunohistochemical staining with appropriate antibodies.
      RESULTS: Labeling of DNA in situ indicated that apoptotic cells were sporadically
      seen in postmenopausal endometrium (5.2 +/- 2.1, n = 4). In contrast, cells
      undergoing apoptosis apparently were detected in endometrioid carcinoma (29.3 +/-
      3.7, n = 20), and their numbers increased intensely in clear cell (49.5 +/- 5.6,
      n = 5) and serous carcinomas (50.8 +/- 6.0, n = 3). Autoradiographic analysis
      revealed that high-molecular-weight DNA was predominant in postmenopausal
      endometrium. However, a DNA ladder was identified in 7 of 10 carcinomas. Although
      Bcl-2 was immunonegative or faintly immunopositive in all cases, many cases of
      endometrioid carcinoma (43.6 +/- 4.1%, n = 20) were immunopositive for Bax,
      unlike postmenopausal endometrium (17.6 +/- 6.7%, n = 4). Moreover, the number of
      cells expressing Bax increased in clear cell (60.4 +/- 6.5%, n = 5) and serous
      carcinomas (66.8 +/- 7.6%, n = 3) compared with that in endometrioid carcinoma.
      CONCLUSIONS: These results indicate that apoptosis occurs in a specific
      population of cells in different histologic components of endometrial carcinomas.
      The expression of Bax, but not of Bcl-2, might suggest histologic differentiation
      in endometrial carcinomas.

PMID- 11330947
TI  - Bcl-2 exerts a pRb-mediated cell cycle inhibitory function in HEC1B endometrial
      carcinoma cells.
AB  - OBJECTIVE: In various human tumors the expression of Bcl-2 appears to vary
      significantly during the transformation process. Indeed, in several glandular
      systems, Bcl-2 levels appear to be sustained in premalignant lesions and rather
      low after the malignant change. Since we recently reported that transformed human
      endometrial cells display constitutively low levels of Bcl-2, we set out to
      investigate the biological meaning of this down-regulation. To this end we
      analyzed the effects of Bcl-2 forced overexpression in a moderately
      differentiated endometrial cell line of human origin. METHODS: Bcl-2
      overexpression was obtained by transfecting HEC1B human endometrial
      adenocarcinoma cells with a suitable bcl-2 vector. The effects of Bcl-2
      overepression were evaluated in several transfectants (cell clones and mixed
      populations) by FACS, growth rates, cloning efficiencies, and modification of the
      phosphorylation status of the pRb protein. Accompanying changes in the expression
      of the CDK inhibitor p21(WAF1/CIP1) were evaluated as well. RESULTS: Bcl-2
      overexpression resulted in a reduced cell proliferation rate, decreased cloning
      efficiency, appreciable cell morphology changes, G2/M cell cycle arrest,
      remarkable accumulation of the dephosphorylated form of retinoblastoma protein,
      and a significant rise in p21(WAF1/CIP1). CONCLUSIONS: From these observation it
      may be deduced that the observed loss and down-regulation of the antiapoptotic
      protein in endometrial glandular human tumors is not random but possibly related
      to the cellular transformation process. It may be also inferred that the
      coincidence of a progressive fading of both Bcl-2 and cyclin inhibitor
      p21(WAF1/CIP1) expressions, together with accumulation of the hyperphosphorylated
      form of the retinoblastoma protein, may be seen as a potential indicator of
      ongoing malignant changes.

PMID- 11330948
TI  - Postoperative vaginal vault brachytherapy for node-negative Stage II (occult)
      endometrial carcinoma.
AB  - OBJECTIVE: The aim of this study is to look at the efficacy of extended surgical
      staging and postoperative vaginal vault brachytherapy in patients with Stage II
      (occult) endometrial carcinoma. METHODS: Between January 1989 and December 1997,
      there were 30 patients with Stage II (occult) endometrial carcinoma who received
      postoperative vaginal vault brachytherapy as the only adjuvant treatment. The
      study group consisted of 15 of these patients who had extended surgical staging
      (including lymphadenectomy). RESULTS: At a median follow-up of 36 months (range
      17 to 113 months), there has been no recurrence. There were no major
      complications from surgery. Only 1 patient had mild rectal bleeding following
      vaginal vault brachytherapy and there were no grade 3 or 4 bowel toxicities.
      CONCLUSIONS: Extended surgical staging and postoperative vaginal vault
      brachytherapy for Stage II (occult) endometrial carcinoma is associated with
      minimal morbidity and excellent survival.

PMID- 11330949
TI  - Tumor distribution and survival in six patients with brain metastases from
      cervical carcinoma.
AB  - OBJECTIVE: The aim of this study was to investigate the patterns of brain
      involvement and the outcome of patients with brain metastases from cervical
      carcinoma. METHODS: Between January 1982 and November 1999, 1279 patients with
      brain metastases were treated at the Cleveland Clinic. Six of them had brain
      metastases from cervical carcinoma. We retrospectively reviewed the patient and
      tumor characteristics at the time of the primary diagnosis as well as at the time
      of the brain metastases diagnosis. RESULTS: Brain metastases from cervical
      carcinoma were rarely accompanied by systemic disease, but they were commonly
      accompanied by uncontrolled local-regional disease. The median interval from the
      appearance of the primary carcinoma to the detection of brain metastases in 5
      patients was 12 months. Multiple brain lesions developed in 4 of 6 patients and
      consisted of multiple tumors distributed in the cerebral hemispheres (2 patients)
      or both the cerebral and the cerebellar hemispheres (2 patients). Only 2 patients
      had a single lesion confined to a cerebral hemisphere. One patient was treated
      with stereotactic radiosurgery alone, 3 with surgery followed by whole brain
      radiation therapy, 1 with whole brain radiotherapy, and 1 each with whole brain
      radiotherapy and stereotactic radiosurgery. Patients treated with surgery had a
      median survival of 8.25 months, while patients treated with whole brain
      radiotherapy with or without stereotactic radiosurgery had a median survival of
      3.75 months. The 1 patient treated with stereotactic radiosurgery alone survived
      for 22.5 months. CONCLUSION: Although the number of the patients was too small to
      detect definitive patterns of brain metastases from cervical carcinoma, the
      results of our review suggest that, in contrast to previous reports, extended
      survival can occur with more aggressive treatment such as surgery or stereotactic
      radiosurgery.

PMID- 11330950
TI  - Chronic administration of single-agent paclitaxel in gynecologic malignancies.
AB  - OBJECTIVE: There are currently limited published data available on the safety and
      feasibility of the prolonged administration of paclitaxel. The goal of this study
      was to review the cumulative toxicity associated with the continuous long-term
      administration of this agent to women with gynecologic cancers. METHODS: Eleven
      patients with gynecologic malignancies of varying histologic subtypes who
      received >15 consecutive courses of paclitaxel were identified in a retrospective
      review of individuals treated between 1994 and 1999 in the Gynecologic Oncology
      Program of the Cleveland Clinic Taussig Cancer Center. The analysis excluded
      paclitaxel delivered as a component of an initial chemotherapy regimen for the
      cancer. Paclitaxel was administered at doses ranging from 80 to 175 mg/m(2) every
      3-4 weeks as a 3-h infusion. RESULTS: In general, the patients included in this
      report were heavily pretreated and were continued on therapy either as a result
      of documentation of an objective response or with evidence of stabilization of
      disease (e.g., physical examination, radiographic evaluation, CA-125 antigen
      level) and the maintenance of a satisfactory quality of life. In the 11 patients,
      the median duration of therapy was 20 cycles (range: 16-36 cycles). Alopecia was
      observed in all patients. A single patient experienced grade 3 anemia and grade 4
      neutropenia. Of note, there was 1 case of grade 2 and no cases of grade 3
      peripheral neuropathy in this population. CONCLUSION: Prolonged delivery of
      paclitaxel for >15 consecutive cycles can be safely administered to carefully
      selected patients with persistent or recurrent advanced gynecologic cancers.

PMID- 11330951
TI  - The clinical utility of liposomal doxorubicin in recurrent ovarian cancer.
AB  - OBJECTIVES: The aim of this study was to determine the efficacy and toxicity of
      single agent off-protocol, liposomal doxorubicin (Doxil Alza), in consecutive
      patients with recurrent ovarian cancer and to investigate the influence of HER
      2/neu expression on response to liposomal doxorubicin. PATIENTS AND METHODS:
      Retrospective analysis of 72 consecutive patients treated, typically with
      liposomal doxorubicin 40 mg/m(2) q28 days between January 1997 and December 1998.
      Results. Twenty-nine patients (40%) had platinum- and taxane-resistant tumors.
      Nineteen patients (27%) responded with clinical or radiological evidence of
      response with reduction in CA-125 of >50%. One complete response (CR) and 7
      partial responses (PRs) occurred in platinum- and taxane-resistant patients
      (radiological response (RR) 29%) and 8 PRs occurred in patients with visceral
      metastases (RR 28%). Time to progression was 5.3 (2.1-12.1) months. Only 7 dose
      delays (3%) and 20 dose reductions (8%) were necessary in 265 cycles of
      treatment. Hematological toxicity was generally mild with grade (Gr) > or =III
      neutropenia in 1 (2%), Gr > or =III thrombocytopenia in 1 (1%), and Gr > or =III
      anemia in 8 patients (11%). One patient (1%) was admitted with fever and
      neutropenia. Other toxicity was minimal with Gr > or =III mucositis occurring in
      3 patients (4%). Gr > or =III cutaneous toxicity was seen in 6 patients (8%).
      Three patients (4%) had a >10% fall in ejection fraction but there was no
      unequivocal clinical heart failure. CONCLUSIONS: The data suggest that liposomal
      doxorubicin is an active drug in both taxane- and platinum-sensitive and
      resistant recurrent ovarian cancer. Liposomal doxorubicin is associated with
      tolerable toxicity and is particularly well tolerated in patients with multiple
      prior lines of treatment.

PMID- 11330952
TI  - Repetitive high-dose topotecan, carboplatin, and paclitaxel with peripheral blood
      progenitor cell support in previously untreated ovarian cancer: results of a
      Phase I study.
AB  - OBJECTIVE: In view of the significant activity of topotecan in ovarian cancer
      with dose-limiting toxicity (DLT) of myelosuppression, we evaluated the addition
      of topotecan to carboplatin and paclitaxel with peripheral blood progenitor cell
      (PBPC) support. METHODS: Patients with previously untreated stage IIIC or IV
      ovarian cancer with macroscopic residual disease following primary debulking
      surgery were eligible. Patients received two cycles of carboplatin AUC = 5 and
      175 mg/m(2) of paclitaxel with collection of PBPCs after the second cycle.
      Patients subsequently received three cycles of high-dose therapy (HDT) with
      topotecan on a daily x5 schedule, paclitaxel (250 mg/m(2) over 24 h), and
      carboplatin (AUC = 12-16). RESULTS: Nineteen patients with a median age of 49
      years (range 21-63) were enrolled and topotecan was escalated in 6 patient
      cohorts up to a dose of 4.5 mg/m(2)/day. Fifty-two of the planned 57 treatment
      cycles were delivered with no treatment-related deaths. Neutrophil and platelet
      recovery was rapid and the interval between HDT was 28 days. Febrile neutropenia
      occurred following 57% of all HDT cycles. DLTs of mucositis and diarrhea were
      observed at topotecan (4.5 mg/m(2)/day), paclitaxel (250 mg/m(2)) and carboplatin
      (AUC = 12). The protocol was subsequently modified to administer topotecan (2.5
      mg/m(2)/day) with carboplatin (AUC = 16); however, 2 patients developed grade 4
      diarrhea (1 with grade 3 mucositis and 1 with grade 4 mucositis). The clinical CR
      rate was 73% (14/19) with an overall clinical response rate of 95% (18/19). Of
      the 14 patients with a CCR, 13 of these underwent a second-look laparotomy with 8
      (61%) achieving a pathological CR. With a median follow-up of 28 months (range 11
      40 months), the median PFS is 36 months and OS has not been reached. CONCLUSION:
      When combined with carboplatin (AUC = 12) and paclitaxel (250 mg/m(2)), the
      recommended topotecan dose is 3.5 mg/m(2)/day for 5 days. This outpatient HDT
      regimen combines three of the most active drugs in ovarian cancer with acceptable
      toxicity and promising activity.

PMID- 11330953
TI  - Comparison of three risk of malignancy indices in evaluation of pelvic masses.
AB  - OBJECTIVES: The aims of this study were to validate the risk of malignancy index
      (RMI) incorporating menopausal status, serum CA 125 levels, and ultrasound
      features for discriminating benign from malignant pelvic masses and to evaluate
      the performance of the three different risk of malignancy indices (RMI 1, RMI 2,
      and RMI 3). METHODS: This is a retrospective study of 152 women admitted at
      Kasturba Hospital, Manipal, between January 1997 and August 1999 for surgical
      exploration of pelvic masses. The sensitivity, specificity, and positive
      predictive value of serum CA 125 levels, ultrasound findings, and menopausal
      status were taken separately and combined into the RMI 1, RMI 2, and RMI 3 to
      diagnose ovarian cancer. The risk of malignancy index is the product of
      menopausal score, ultrasound score, and serum CA 125 levels. RESULTS: The study
      confirms that the malignancy risk index is more accurate than the menopausal
      status, serum CA 125 levels, and ultrasound features separately in diagnosing
      malignancy. There was no statistically significant difference in the performance
      of these three different malignancy risk indices in identifying malignancy.
      CONCLUSIONS: The risk of malignancy index is able to identify malignant and
      benign pelvic masses efficiently to optimize therapy. The risk of malignancy
      index is a simple scoring system which can be used in less specialized gynecology
      centers. We recommend the use of any of these risk of malignancy indices to
      facilitate the selection of cases for referral to an oncological unit for
      adequate staging and optimal debulking.

PMID- 11330954
TI  - Accuracy of intraoperative frozen section diagnosis of ovarian tumors.
AB  - OBJECTIVE: The goal of this work was to evaluate retrospectively, as quality
      control, the accuracy of frozen section diagnosis in ovarian tumors. METHOD: We
      compared 243 frozen section results with the final diagnosis in paraffin
      sections, from cases studied from January 1994 to April 1999. RESULTS: Results
      with the two methods were analyzed on two parameters: (a) malignant potential and
      (b) histological type. As for malignant potential, frozen section diagnosis
      agreed with the paraffin diagnosis in 94% of all cases (98.5% for malignant
      tumors, 94% for benign tumors, and 78.6% for borderline tumors). There was one
      false-positive and 13 false-negative cases. Sensitivity and specificity values
      for malignant tumors were 93 and 99%; for borderline tumors, 61 and 99%; and for
      benign tumors, 98 and 93%. With respect to histological type, in 203 cases (84%)
      the pathologists had no doubt in the diagnosis; in 40 cases (16%) diagnosis was
      given as "compatible with." In 35 of these (87.5%) the initial diagnosis was
      confirmed by paraffin. CONCLUSION: Frozen section diagnosis seems to be a
      reliable method for ovarian tumors, with high sensitivity for malignant neoplasms
      and a low false-positive rate which allow the best choice of treatment. The most
      frequent problems arise with borderline and granulosa cell tumors.

PMID- 11330955
TI  - Time since last birth and the risk of ovarian cancer.
AB  - OBJECTIVES: While parity is a protective factor in ovarian cancer, the role of
      time factors of pregnancy and birth is still controversial. We considered
      therefore the role of birth timing in the risk in ovarian cancer from a large
      case-control study. METHODS: Cases were 971 women (age range 22-74 years, median
      age 54) with histologically confirmed, incident epithelial ovarian cancer,
      interviewed between 1983 and 1991 in a network of hospitals in Milan, Italy.
      Controls were 2758 women (age range 23-74 years, median age 52) admitted to the
      same hospitals where cases were identified for acute, nonneoplastic conditions.
      RESULTS: In comparison with nulliparous women, the multivariate odds ratios (OR)
      were 0.8 for women reporting one or two and 0.6 for those with three or more
      births. No clear association emerged between time since last birth and ovarian
      cancer. Compared to women who had last given birth since > or =20 years, a
      moderately increased risk of ovarian cancer was observed in the first 10 years
      after last birth, with an OR of 1.7 (95% confidence interval, CI 1.0-2.9). When
      we considered only multiparous women and included in the multivariate analysis
      allowance for age at first birth, the OR decreased to 1.2 (95% CI 0.6-2.4). No
      consistent pattern of trends was observed > or =10 years since last pregnancy.
      CONCLUSIONS: This study confirms the protective effect of parity on ovarian
      carcinogenesis, but shows no consistent pattern of risk across time since last
      birth.

PMID- 11330956
TI  - Secondary cytoreductive surgery for localized intra-abdominal recurrences in
      epithelial ovarian cancer.
AB  - OBJECTIVE: The aim of this study was to evaluate the role of secondary
      cytoreductive surgery in patients with recurrent epithelial ovarian cancer with
      an apparent solitary intra-abdominal focus. METHODS: We conducted a retrospective
      review of patients with epithelial ovarian cancer who underwent secondary
      cytoreduction for recurrence at the University of Texas M. D. Anderson Cancer
      Center between 1985 and 1994. Eligible patients included those who had a
      laparotomy to resect a tumor that was apparently solitary. Cytoreductive surgery
      was defined as optimal if the diameter of the largest residual tumor was < or =2
      cm and suboptimal if >2 cm. RESULTS: Twenty-five patients met our eligibility
      criteria. Their mean age was 55 years (range, 35-73 years). The median time from
      primary diagnosis to recurrence was 37.6 months. Tumor was found to be confined
      to a solitary site in 15 patients (60%), to two sites in 6 (24%), and to three or
      more sites in 4 (16%). Surgical procedures included cytoreduction in 10 patients,
      intestinal resection in 8, splenectomy in 3, and limited biopsies in 4. Secondary
      cytoreduction was optimal in 18 of 25 patients (72%). The median postsecondary
      cytoreduction survival was 25.1 months for patients who had suboptimal secondary
      cytoreduction compared with 56.9 months for those who had optimal cytoreduction
      (P = 0.08). CONCLUSIONS: Secondary cytoreductive surgery for recurrent ovarian
      cancer at an apparently solitary intra-abdominal site resulted in optimal
      residual tumor in a high proportion of patients. Although there was no survival
      advantage for patients whose tumor was optimally debulked, there was a trend
      toward improved survival. A large prospective randomized trial of secondary
      cytoreduction for recurrence is recommended.

PMID- 11330957
TI  - The role of p27 in endometrial carcinoma.
AB  - OBJECTIVE: The cyclin-dependent kinase inhibitor p27 has been shown to mediate
      cell growth arrest in response to various environmental stimuli. p27 protein
      levels have shown prognostic value in several different types of cancer. We
      examined the prognostic value of p27 protein expression in endometrial cancer,
      the most common gynecologic malignancy. METHODS: A total of 95 paraffin-embedded
      tumor blocks were obtained and stained via immunohistochemical techniques with a
      monoclonal antibody against p27. Ten high-power fields were evaluated per slide
      with at least 1000 cells per slide and two slides per specimen evaluated by two
      reviewers for nuclear and cytoplasmic staining. The specimens were evaluated for
      associations with age, stage, grade, and histology. Statistical analysis was
      performed using the Student t test, chi(2) Kaplan-Meier, and likelihood ratios to
      assess the data and to generate P values. RESULTS: A total of 91 patients met
      inclusion criteria for statistical analysis. Fifty-three patients were stage I,
      13 stage II, 14 stage III and 11 stage IV with a positive stain (>50% of cells)
      for p27 obtained in 32.1, 23.1, 35.7, and 36.4%, respectively (Student t test P =
      0.77). Survival data were available on 24 advanced stage patients. p27 protein
      immunostaining showed no association with patient survival. We also found no
      association of p27 staining with age or histology. Notably, we found a trend in
      increasing staining with increase in grade, particularly with stage I patients.
      Also, there was an association of the nuclear and cytoplasmic staining and stage
      (P = 0.05), but it had no correlation with patient survival. CONCLUSION: Our
      study showed decreased p27 protein staining in endometrial cancers compared to
      normal endometrial cells. We found that p27 protein staining shows no association
      with stage, age, or histology and is not prognostic for survival in advanced
      endometrial cancers. However, there may be a trend associated with increased p27
      protein staining with advanced grades of tumors.

PMID- 11330958
TI  - Genetic origin of malignant trophoblastic neoplasms analyzed by sequence tag site
      polymorphic markers.
AB  - OBJECTIVE: To study the causative conception of malignant gestational
      trophoblastic neoplasms (GTNs), we analyzed malignant GTNs by microsatellite PCR
      markers. METHOD: DNAs extracted from 12 malignant GTNs were subjected to PCR for
      five different chromosomal locations. RESULT: Of the 7 cases after a complete
      mole (CM), 5 were derived from androgenesis, but the remaining 2 were from normal
      fertilization. Of the 5 cases after nonmolar pregnancies, 2 placental site
      trophoblastic tumors had alleles from both parents. Of the other 3
      choriocarcinomas, 1 was from normal fertilization after spontaneous abortion but
      2 originated from androgenesis, suggesting that 1 was from a CM prior to the
      antecedent abortion, transforming after a long interval. CONCLUSION: By combining
      the previous cases with these, our analysis of 39 cases demonstrated that
      trophoblastic neoplasms can arise from at least three different modes of origin
      (androgenesis, normal fertilization, and parthenogenesis), and antecedent
      pregnancy is not always identical to the causative conception. Placental site
      trophoblastic tumors might have different machinery for carcinogenesis because of
      the predominance of paternal and maternal contributions. In addition, a long
      dormancy of trophoblasts before malignant transformation, especially for those
      originating from normal fertilization, was also suggested.

PMID- 11330959
TI  - The effects of sex, menstrual cycle, and oral contraceptives on the number and
      activity of natural killer cells.
AB  - OBJECTIVES: The aim of this study was to study the impact of sex, the menstrual
      cycle, and the use of oral contraceptives (OC) on the number and activity of
      natural killer (NK) cells. METHODS: Both the number and the activity of NK cells
      were assessed per milliliter of blood, and NK activity (NKA) per NK cell and per
      lymphocyte was calculated. NKA was measured in each subject using a whole blood
      assay, which preserves the plasma and all blood cells, and using a washed blood
      assay, in which plasma is replaced with an artificial medium. The subjects were
      young (20-29 years old) women with a regular menstrual cycle (n = 39; 26 tested
      on both the follicular and the luteal phases), age-matched women who use OC (n =
      26), and age-matched men (n = 20). RESULTS: Men showed markedly and significantly
      higher NKA than women with regular menstrual cycles or women using OC, who had
      the lowest levels of NKA. No significant differences in blood concentration of NK
      cell were found. Differences in NKA were of similar magnitude in the whole and
      washed blood assays per milliliter of blood, per NK cell, or per lymphocyte. The
      menstrual cycle had no significant effect on activity levels of NK cells, but
      during the periovulatory phase, the number of NK cells per milliliter of blood
      increased significantly. CONCLUSIONS: The observed differences are independent of
      the presence of serum factors during the in vitro assessment of NKA, but may be
      related to chronic exposure to sex steroids and to fluctuation in the NK cell
      expression of beta-adrenoceptors.

PMID- 11330960
TI  - CYP1A1, GSTM1, and GSTT1 polymorphisms and the risk of cervical squamous
      intraepithelial lesions in a multiethnic population.
AB  - OBJECTIVE: In this investigation, we explored the hypothesis that genetic
      polymorphisms in the cytochrome P4501A1 (T3801C) and glutathione S-transferase
      classes mu and theta (GSTM1 and GSTT1) gene deletions promote the development of
      cervical dysplasia by moderating the activation and detoxification of polycyclic
      hydrocarbons and other compounds that influence oxidative stress and DNA adduct
      formation. METHODS: A multiethnic, case-control study of 131 women with biopsy
      confirmed cervical squamous intraepithelial lesions (SIL) and 180 controls with
      cytologically normal cervical (Pap) smears was conducted between 1992 and 1996 in
      Honolulu, Hawaii. We collected in-person interviews, a blood sample to extract
      genomic DNA, and an exfoliated cervical cell sample to determine the presence and
      type of human papillomavirus (HPV) using PCR dot-blot hybridization. Genotyping
      for the CYP1A1 MspI allelic variant and deletion of the GSTM1 and GSTT1 gene loci
      followed a PCR method. RESULTS: Women who were homozygous, but not heterozygous,
      for the CYP1A1 MspI variant allele were at significantly increased risk of
      cervical SIL (odds ratio (OR) = 3.4; 95% confidence interval (CI) = 1.1-10.7)
      compared to women who were homozygous for the wild-type allele. Subjects with the
      GSTM1 null genotype had a nonsignificant elevated risk of cervical SIL (OR = 1.6;
      95% CI = 0.8-3.0) compared to women with the gene present. No difference in the
      risk of cervical disease was associated with the GSTT1 null genotype. The
      combination of the CYP1A1 homozygous variant and the GSTM1 null genotypes
      increased the odds ratio for cervical SIL to 5.1 (95% CI = 1.3-20.7). There was
      no evidence for an interaction between genotype and exposure to tobacco smoke,
      alcohol drinking, or HPV DNA positivity. CONCLUSIONS: These findings, although
      based on a small number of subjects, suggest that the CYP1A1 MspI polymorphism
      may be a susceptibility factor for early, premalignant changes in the cervical
      epithelium.

PMID- 11330961
TI  - Importance of urodynamic study before radical hysterectomy for cervical cancer.
AB  - OBJECTIVES: The aim of this study was to characterize the urodynamic findings in
      patients with cervical cancer before radical hysterectomy and to correlate the
      results with age, parity, menopausal status, and cancer stage. METHODS: All
      patients with cervical cancer before radical hysterectomy who underwent
      urodynamic study (UDS) from January 1996 through December 1998 were enrolled.
      Detailed history, physical examination, and multichannel UDS data including
      uroflowmetry, filling and voiding cystometry, stress urethral pressure profile,
      and 20-min pad test were obtained for each patient. The urodynamic findings of
      each patient were analyzed and correlated with age, parity, menopausal status,
      and cancer stage. RESULTS: A total of 210 patients with cervical cancer were
      included in the study. The mean age was 48.9 +/- 10.5 years with a mean parity of
      3.3 +/- 1.7. Forty-two percent (n = 88) of patients were menopausal, and 88% (n =
      184) belonged to stage IB while 10% (n = 20) were stage IIA and 2% (n = 6) stage
      IIB. Urodynamic study showed that only 17% (n = 37) of the 210 patients were
      normal, 10% (n = 21) had voiding dysfunction, 45% (n = 94) had storing
      dysfunction, and 28% (n = 58) had both voiding and storing dysfunctions. In
      addition, 51% (n = 106) had urinary incontinence and 37% (n = 78) had genuine
      stress incontinence (GSI), 8% (n = 16) detrusor instability (DI), and 6% (n = 12)
      GSI/DI. Age, parity, and cancer stage did not show any significant differences
      among these four groups. CONCLUSIONS: In this series, only 17% of patients with
      cervical cancer had normal urodynamic findings before radical hysterectomy.

PMID- 11330962
TI  - Analysis of FIGO Stage IIIc endometrial cancer patients.
AB  - OBJECTIVE: The aim of this study was to analyze FIGO Stage IIIc endometrial
      cancer (EC) patients to better define clinicopathologic associations, patterns of
      failure, and survival. METHODS: Charts were abstracted from EC patients with
      lymph node metastasis from 1989 to 1998. Data on clinicopathologic variables,
      adjuvant treatment, site of first recurrence, and survival were collected.
      Associations between variables were tested by chi(2) and Wilcoxon rank sums.
      Survival analyses were performed by the Kaplan-Meier method, and multiple
      regression analysis was done by the Cox proportional hazards model. RESULTS: From
      607 EC patients evaluated, 47 (8%) were identified with FIGO Stage IIIc disease.
      All 47 underwent hysterectomy and pelvic lymph node (PLN) sampling, and 42/47 had
      para-aortic lymph node (PALN) sampling. Stage IIIc disease was defined by
      positive PLN alone in 38%, positive PLN and PALN in 41%, and positive PALN alone
      in 17%. Twelve of 47 also had positive peritoneal cytology and/or adnexal
      metastases. Grade III tumors were present in 56% and >50% myometrial invasion in
      61%. No association between depth of invasion (DOI) and grade was seen, however.
      Nearly 1/3 of cases had papillary serous or clear cell histology. Postoperative
      adjuvant treatment included whole abdominal radiation (36%), pelvic radiation
      with (19%) and without (17%) extended field, chemotherapy (17%), and oral
      progestins (11%). The 3-year and 5-year survival estimates for all patients were
      77 and 65%, respectively. At a median follow-up of 37 months, 5 patients are
      alive with disease, and 10 are dead of disease. A distant site of first
      recurrence was most common (21%), followed by pelvic failure (9%). Only 1 patient
      has had an abdominal recurrence. Univariate predictors of survival included age,
      DOI, and extranodal disease, but not grade, histology, or PALN involvement. For
      the 12 patients with nodal disease and positive cytology and/or adnexa, 3-year
      survival was 39% versus 93% for those patients without evidence of extranodal
      disease. In a multivariate analysis only DOI was an independent predictor of
      survival (P = 0.03). CONCLUSIONS: Once lymph node involvement occurs, the
      importance of additional extranodal disease increases. Consideration of
      substaging Stage IIIc patients based on positive adnexa or cytology is supported
      by the data. The extent which adjuvant treatments contributed to the 77% 3-year
      survival remains to be defined. The patterns of failure suggest a possible role
      for combined modalities in future treatments.

PMID- 11330963
TI  - Extended surgical staging for uterine papillary serous carcinoma: survival
      outcome of locoregional (Stage I-III) disease.
AB  - OBJECTIVE: The aim of this study was to evaluate survival outcome in patients
      with locoregional uterine papillary serous carcinoma (UPSC) after extended
      surgical staging (ESS). METHODS: All patients diagnosed with FIGO Stage I-III
      UPSC undergoing ESS (vertical incision, peritoneal cytology, TAH/BSO, omental
      biopsy, lymph node sampling, peritoneal biopsy) between 1/1/89 and 12/31/98 were
      identified retrospectively from the tumor registry database. Pathologic features
      predictive of regional extrauterine spread were evaluated using the log-rank
      test. The Kaplan-Meier method was used to generate survival curves, and median
      survival determinations were compared using the log-rank test or the proportional
      hazards regression model. RESULTS: Twenty-six patients with locoregional UPSC
      were identified: FIGO Stage I (n = 11), Stage II (n = 7), and Stage III (n = 8).
      The median age at diagnosis was 66 years. Preoperative endometrial pathology
      correctly identified the presence of UPSC in 76.9% of cases. The only pathologic
      feature found to be predictive of regional extrauterine spread (Stage III) was
      myometrial invasion > or =50% (P = 0.028). Adjuvant radiation therapy (RT) was
      administered to 6/18 patients with Stage I/II disease and 5/8 patients with Stage
      III disease. Platinum-based chemotherapy was administered to 5 patients with
      Stage III disease. All recurrences of Stage I/II disease were located within the
      pelvis (16.7%). For Stage III disease, all recurrences occurred at distant sites
      (42.9%). The median follow-up time for surviving patients was 39.0 months (mean =
      45.0 months). For all patients, the overall 5-year survival rate was 61.2%.
      According to FIGO stage, the overall 5-year survival rates were Stage I, 81.8%;
      Stage II, 64.3%; and Stage III, 31.3%. No significant differences were detected
      in the risk of death by stage, although there was a trend toward worse survival
      with Stage III disease: Stage I hazard ratio [HR] = 1.00, Stage II HR = 1.68, 95%
      confidence interval [CI] = 0.23-12.03, Stage III HR = 3.63, 95% CI = 0.65-20.12.
      CONCLUSIONS: Patients with locoregional UPSC following ESS have a more favorable
      prognosis than previously thought. The additional information provided by ESS
      facilitates the selection of adjuvant therapy. Whole pelvic RT is recommended for
      patients with Stage I/II disease. Pathologic Stage III disease portends a
      significant risk of distant recurrence. For these patients, administration of
      adjuvant chemotherapy should be considered in addition to directed RT.

PMID- 11330964
TI  - Breast cancer risk assessment in indigent women at a public hospital.
AB  - OBJECTIVES: The aims of this study were to estimate the 5-year breast cancer risk
      in indigent women presenting to the gynecology clinic at a public hospital and to
      determine whether routine use of the computerized Gail model for screening in
      this population identifies individuals at increased risk. METHODS: A prospective
      study was performed over 1-year period (7/99-7/00) of women presenting to the
      gynecology and gynecologic oncology clinics at a public hospital. All women ages
      35-60 years with no personal history of breast cancer were offered testing
      utilizing the computerized Gail model provided by the National Cancer Institute.
      Age, race, age at menarche, age at first live birth, number of first-degree
      relatives with breast cancer, number of breast biopsies, and number of breast
      biopsies diagnosed as atypical hyperplasia were documented. A calculated 5-year
      risk > or =1.67% was considered high-risk. RESULTS: In all, 319 women enrolled,
      121 (38%) with a history of gynecologic cancer and 198 (62%) without. The mean
      age was 46.9 years (range 35-60), and 28 (8.8%) patients had at least one first
      degree relative with breast cancer. Ethnicity included 206 (65%) African
      American, 52 (16%) Caucasian, 45 (14%) Hispanic, and 16 (5%) oriental. Eight
      (2.5%) women had a 5-year risk > or =1.67%. The mean 5-year risk for all patients
      was 0.68% (0.55% for African American versus 0.90% for Caucasian/other, P <
      0.001). CONCLUSION: Estimating 5-year breast cancer risk using the Gail model in
      indigent women may identify individuals at increased risk. Compared to other
      patients, African American women appeared to have a lower estimated 5-year risk
      according to the currently available model. The routine utilization of the Gail
      model deserves further investigation in the indigent minority population.

PMID- 11330966
TI  - The expression and action of granulocyte macrophage-colony stimulating factor and
      its interaction with TGF-beta in endometrial carcinoma.
AB  - OBJECTIVE: Previous studies have demonstrated that normal human endometrium
      expresses granulocyte macrophage-colony stimulating factor (GM-CSF) and GM-CSF
      receptors. Because GM-CSF is administer to cancer patients following
      chemotherapy, GM-CSF may directly or through interaction with ovarian steroids
      and other cytokines alter the behavior of endometrial cancer. The aim of this
      study was to determine the expression of GM-CSF and receptors in endometrial
      carcinoma and its direct effect and interaction with transforming growth factor
      beta (TGF-beta) on Ishikawa cells, a human endometrial carcinoma cell line.
      METHODS: GM-CSF, GM-CSF receptors, TGF-beta1, and TGF-beta type II receptor
      expression were evaluated using quantitative reverse transcription polymerase
      chain reaction (Q-RT-PCR). The effect of GM-CSF on DNA synthesis, cell
      proliferation, expression of GM-CSF, TGF-beta1, and TGF-beta receptor, and their
      regulation by ovarian steroids was determined by the rate of [(3)H]thymidine
      incorporation, MTT assay, Q-RT-PCR, and ELISA, respectively. RESULTS: Endometrial
      carcinomas express significantly higher GM-CSF and GM-CSF alpha and beta receptor
      mRNA compared with normal postmenopausal endometrium. GM-CSF at various doses had
      no significant effect on the rate of [(3)H]thymidine incorporation or
      proliferation of Ishikawa cells, whereas TGF-beta1 inhibited [(3)H]thymidine
      incorporation. GM-CSF and TGF-beta1 regulate their own expression and the
      expression of TGF-beta type II receptor, which were both upregulated by 17beta
      estradiol and medroxyprogesterone acetate treatment and reversed following
      cotreatment with their respective receptor antagonists. CONCLUSION: Endometrial
      carcinoma expresses an elevated level of GM-CSF and GM-CSF receptors. GM-CSF is
      not a mitogen for the endometrial cancer cell line; however, either alone or
      through interaction with TGF-beta1, it regulates its own expression and the
      expression of TGF-beta1 and TGF-beta type II receptor which inhabits endometrial
      cancer cells. This interaction may represent a regulatory feedback mechanism that
      could serve to suppress endometrial carcinoma growth.

PMID- 11330965
TI  - Lysophospholipids increase interleukin-8 expression in ovarian cancer cells.
AB  - OBJECTIVES: We have previously described that bioactive lysophospholipids
      lysophosphatidic acid (LPA), sphingosine 1-phosphate (S1P), and
      sphingosylphosphorylcholine (SPC)-are present in ascitic fluids from patients
      with ovarian cancer. To understand the role of these lipids in ovarian cancer, we
      investigated the effects of these lipids on interleukin-8 (IL-8) production in
      ovarian cancer cells. IL-8 is a proinflammatory and proangiogenic factor, which
      is potentially involved in ovarian cancer development. METHODS: The Clontech PCR
      Select cDNA subtraction method (Clontech Laboratories, Inc., Palo Alto, CA) was
      used to identify genes potentially regulated by LPA in HEY and OCC1 ovarian
      cancer cell lines. Northern blot analysis was used to confirm and examine IL-8
      mRNA regulation by lysolipids. Enzyme-linked immunosorbent assay (ELISA) was used
      for detecting secreted IL-8. RESULTS: We describe here that LPA, S1P, and SPC
      increased mRNA levels (2- to 7-fold) and protein secretion (2- to 12-fold) of IL
      8 from ovarian cancer cells (HEY, OCC1, and SKOV3) in vitro. These regulations
      were both dose- and time-dependent. All three lipids increased the stability IL-8
      mRNA in HEY cells. In contrast to malignant ovarian cancer cells, immortalized
      human ovarian epithelial cells did not respond to any of these lipids to increase
      the secretion of IL-8, although these cells secreted similar basal levels of IL-8
      (310 pg/ml/10,000 cells). Two breast cancer cell lines (MCF7 and T47D) secreted
      lower basal levels of IL-8 (48-80 pg/ml/10,000 cells), compared with ovarian
      cancer cells (200-500 pg/ml/10,000 cells). MCF7 cells responded to LPA, but not
      S1P and SPC, by increasing the secretion of IL-8. T47D and MCF10A, an
      immortalized breast cell line, did not respond to LPA, S1P, or SPC to increase IL
      8 secretion. CONCLUSIONS: LPA, S1P, and SPC regulate the mRNA and protein levels
      of the proinflammatory and proangiogenic factor IL-8 in ovarian cancer cells. The
      pathological significance of these regulations in ovarian cancer remains to be
      further investigated.

PMID- 11330967
TI  - Term delivery following conservative treatment for villoglandular papillary
      adenocarcinoma of the uterine cervix: report of a case and analysis of the
      literature.
AB  - BACKGROUND: Villoglandularpapillary adenocarcinoma (VPA) of the cervix is often
      indolent, and surgical treatment has a favorable outlook. Risk factors include
      depth of invasion, lymphovascular invasion, and the presence of other histologic
      types of cancer. CASE: An amputation of the cervical portio was required to
      satisfactorily resect a 2.5-cm ectocervical lesion in a 28-year-old nulligravida.
      A diagnosis of pure VPA with a depth of invasion less than 2 mm was established.
      During a subsequent pregnancy, second trimester ultrasound showed extreme
      effacement of her cervix and an abdominal cerclage was placed. The pregnancy
      continued until delivery of a healthy infant at 36 weeks. CONCLUSIONS: In cases
      of tumor invasion less than 3 mm, and in the absence of lymphovascular space
      involvement, extrauterine spread of pure VPA has not been described. When
      conservative treatment is planned, amputation of the cervical portio may be
      better suited than conization to the achievement of an adequate margin of
      resection. Cervical cerclage may be needed to offset the extensive cervical
      surgery.

PMID- 11330968
TI  - Late recurrence in ovarian dysgerminoma with successful response to standard
      adjuvant chemotherapy: a case report and review of the literature.
AB  - BACKGROUND: Ovarian dysgerminomas are quite amenable to treatment and very good
      cure rates are achieved even with advanced disease. However, recent literature
      suggests that late recurrence may be associated with a poorer prognosis and
      bleomycin/etoposide/cisplatin (BEP) chemotherapy may play only a limited role in
      its management. We present a patient who had a late recurrence of ovarian
      dysgerminoma with successful treatment outcome. CASE: A 25-year-old woman was
      diagnosed with a stage IC ovarian dysgerminoma in 1983 and did not undergo
      adjuvant treatment. She had late recurrence 12 years later with good treatment
      response to BEP chemotherapy given in a semiadjuvant fashion. CONCLUSION: Our
      case demonstrates that BEP chemotherapy still plays an important role in
      treatment of late recurrence in ovarian dysgerminomas provided there is small
      volume disease at time of detection. Also important is long-term surveillance in
      an effort to detect recurrence while still small in volume and potentially
      curable.

PMID- 11330969
TI  - Sclerosing stromal tumor in an accessory ovary.
AB  - BACKGROUND: An accessory ovary is an uncommon congenital anomaly of the female
      reproductive tract. Tumors arising in ectopic ovaries are extremely rare. CASE:
      This 18-year-old woman had a pelvic tumor attached to the right ovary which was
      solid cystic and lobulated and histologically and immunohistochemically showed
      the appearances of sclerosing stromal tumor, a benign entity. CONCLUSION: We
      present the first reported case of sclerosing stromal tumor that arose in an
      accessory ovary.

PMID- 11330970
TI  - Sarcoma in association with multimodality management of vulvar cancer: two case
      reports.
AB  - BACKGROUND: Radiation-induced or -associated sarcoma is a rare event which has
      been well described in the literature. However, this entity has been infrequently
      described in association with genital tract malignancies. To our knowledge it has
      never been described in association with the management of vulvar cancer. CASES:
      . Two different cases of sarcoma developing after primary management for vulvar
      cancer are presented, the first being a case of angiosarcoma developing in the
      lower abdominal wall 36 months after initial therapy and the second a case of
      fibrosarcoma developing on the vulva 7 years after multimodality treatment.
      CONCLUSION: Radiation-associated sarcoma after treatment for vulvar carcinoma is
      a rare event. A multimodality treatment of carcinoma of the vulva should not be
      withheld because of fear of sarcomagenesis.

PMID- 11330971
TI  - Inguinal lymph node metastasis: an unusual presentation of fallopian tube
      carcinoma.
AB  - OBJECTIVES: Inguinal metastasis is a hitherto unreported presenting feature of
      fallopian tube adenocarcinoma. CASE: We describe a case of a 69-year-old patient
      whose first manifestation of fallopian tube adenocarcinoma was an enlarged
      inguinal lymph node. This was excised and confirmed to be metastatic
      adenocarcinoma. She was investigated by diagnostic laparoscopy and subsequently
      underwent laparotomy with total abdominal hysterectomy, omentectomy, and pelvic
      and para-aortic lymph node dissection. All but two of the lymph nodes extirpated
      were negative. CONCLUSIONS: Fallopian tube adenocarcinoma may rarely present with
      metastatic inguinal lymphadenopathy.

PMID- 11330972
TI  - Cellular angiofibroma of the vulva.
AB  - BACKGROUND: The cellular angiofibroma is a benign mesenchymal neoplasm that
      clinically and histologically must be distinguished from biologically more
      aggressive lesions. It typically arises in women of late reproductive age and
      lends itself to cure by complete local excision. A report of an unusual case in a
      postmenopausal patient is presented. CASE: A 77-year-old woman presented with a
      painless vulvar mass that slowly enlarged over 3 years. Past history included a
      hysterectomy and bilateral salpingo-oophorectomy followed by estrogen replacement
      therapy. Surgical excision of the mass was performed and there is no evidence of
      recurrence 1 year postoperatively. Histopathologic examination revealed an
      admixture of hyalinized blood vessels and loose cellular stroma characteristic of
      a cellular angiofibroma. Immunohistochemical studies revealed stromal cell
      immunoreactivity for vimentin and CD34 and nonreactivity for desmin, actin, and
      S100 protein. The nuclei of the stromal cells demonstrated strong reactivity for
      estrogen and progesterone receptors. CONCLUSION: Mesenchymal lesions of the vulva
      and perineum include both benign and malignant neoplasms. The cellular
      angiofibroma is benign; however, other lesions including the aggressive
      angiomyxoma must be excluded when arriving at that diagnosis. The role of long
      term estrogen therapy in the genesis of this tumor awaits further analysis.

PMID- 11330973
TI  - Impact on survival following successful neoadjuvant chemotherapy and radical
      surgery for Stage IIb bulky and Stage IIIb cervical cancer.

PMID- 11330974
TI  - Phase II trial of topotecan, carboplatin, and paclitaxel as front-line therapy in
      suboptimal advanced epithelial ovarian cancer.

PMID- 11330975
TI  - Effects of shakuyaku-kanzo-to on muscle pain from combination chemotherapy with
      paclitaxel and carboplatin.

PMID- 11330976
TI  - Dependence of 13C NMR chemical shifts on conformations of rna nucleosides and
      nucleotides.
AB  - Cross-polarization magic-angle spinning solid-state NMR spectroscopy has been
      used to investigate the dependence of (13)C sugar chemical shifts on specific
      conformational parameters of a variety of ribonucleotides and ribonucleosides.
      Solid-state NMR is a valuable tool for nucleoside and nucleotide structural
      studies since it provides the means to acquire spectra that correspond to single
      conformations, as opposed to (13)C solution NMR methods. The distinct effects of
      sugar puckering on the C1', C4', and C5' resonances of C2' endo (S type) and C3'
      endo (N type) furanoid conformations allow us to separate them into two groups.
      Further analysis of each group reveals an additional dependence of the C1' and
      C5' resonances on the glycosidic and C4'-C5' exocyclic torsion angles,
      respectively. However, it is found that the glycosidic conformation cannot
      independently be determined from sugar (13)C chemical shift data. The statistical
      methods of exploratory data analysis and discriminant analysis are used to
      construct two canonical coordinates-linear combinations of chemical shifts which
      give the statistically optimal determination of the conformation from the NMR
      data.

PMID- 11330977
TI  - Determination of quadrupole parameters with a composite pulse for spurious signal
      suppression.
AB  - Spurious signals such as the piezoelectric signal from a ferroelectric crystal or
      the ringing signal from the NMR probe head tuned for low gyromagnetic ratio
      nuclei are often observed in pulsed NMR. Both signals are cancelled using the
      Hahn echo sequence with appropriate phase cyclings. The present paper applies a
      composite-pulse sequence to cancel the ringing signal. The main advantage of this
      sequence over the Hahn echo sequence is in the simplicity of optimizing the line
      intensity: the optimization of only one pulse duration for this sequence but of
      two pulse durations and the interpulse delay for the Hahn echo sequence. We are
      interested in half-integer quadrupole spins (I = 3/2, 5/2, 7/2, and 9/2), which
      means that we must consider the first-order quadrupole interaction during the
      pulses. For simplicity, we deal mainly with spin I = 3/2 nuclei. Since the
      central-line intensity depends on the ratio of the quadrupole coupling constant
      (QCC) to the amplitude of the RF pulse, we can determine the QCC from a
      featureless lineshape by fitting the variation of the experimental central-line
      intensity for increasing pulse duration with theoretical results. Contrary to the
      one-pulse sequence where the central-line intensity is proportional to the pulse
      duration if the latter is short, there is no such condition with the composite
      pulse sequence. In other words, this sequence does not allow us to quantify the
      relative spin populations in powders. The size of the sample must be much smaller
      than that of the RF coil in order for the RF magnetic field to become homogeneous
      for the sample. We used (87)Rb (I = 3/2) in an aqueous solution of RbCl and in
      RbNb2O5F powder, (131)Xe (I = 3/2) of xenon gas physisorbed in Na-Y zeolite, and
      (23)Na (I = 3/2) in two well-known powders (NaNO3 and NaNO2) to support our
      theoretical result.

PMID- 11330978
TI  - The effects of slice-selective excitation/refocusing in localized spectral
      editing with gradient-selected double-quantum coherence transfer.
AB  - Spectral editing using gradient-selected double-quantum filtering (DQF) with
      PRESS localization has been used for selective observation of metabolites in
      vivo. In previous studies using localized DQF sequences, it is generally assumed
      that the slice-selective pulses used in the sequence have no roles in coherence
      transfer, and do not interfere with DQF. To validate this assumption, the effects
      of slice-selective excitation/refocusing on DQF were investigated in DQF lactate
      editing sequences combined with PRESS localization. Contrary to the previous
      assumption, the results show that, due to chemical shift displacement artifact
      and J coupling, slice selection in DQF does interfere with coherence transfer,
      affecting both the accuracy of spatial localization and the detection sensitivity
      adversely. In the case of lactate editing, the effects of this interference can
      be accounted for simply by adjusting the strength of the slice-selection
      gradients and by using narrowband slice-selective refocusing pulses.

PMID- 11330979
TI  - A time-resolved EPR study of the electron-spin-polarization pathways of p
      benzosemiquinone.
AB  - Benzoquinone (BQ), deuterobenzoquinone (d4-BQ), and hydroquinone (BQH2) are
      investigated in ethylene glycol by means of direct detection fast time-resolved
      EPR spectroscopy after laser flash photolysis. The development of the
      magnetization as a function of time and magnetic field is obtained and analyzed
      in terms of the Bloch equations and hyperfine parameters. The signals are
      attributed to the semiquinones BQH(*) and d4-BQH(*). The presence of 1,2
      dihydroxyethyl radicals during the photolysis of BQ and d(4)-BQ is verified. No
      alkyl radicals are observed in solutions of BQ with excess BQH2. Detailed
      analysis of the chemically induced dynamic electron polarization spectra with
      respect to their development in time shows that polarization patterns of the
      semiquinones can be traced back to a superposition of triplet mechanism and
      radical pair mechanism, the latter arising from geminate T-pairs. Hence, two
      independent pathways for polarization are assumed: reaction of triplet
      benzoquinone with ethylene glycol leads to the semiquinone and dihydroxyethyl
      radicals with all signals in emission, whereas the reaction of triplet BQ and
      BQH2 yields two semiquinones exhibiting both net emissive and multiplet
      emissive/absorptive intensity distributions.

PMID- 11330980
TI  - Diffusion-broadened velocity spectra of convection in variable-temperature BP-LED
      experiments.
AB  - When NMR diffusion experiments are performed at temperatures different from
      ambient temperature, temperature gradients due to probe design can cause thermal
      convection and therefore significantly affect the signal amplitude. Fourier
      transformation of the signal amplitude gives rise to a diffusion-broadened
      velocity spectrum, which contains information about the convection velocity. It
      is shown that when the diffusion broadening factor is smaller than the maximum
      velocity, the broadening has little effect on the determination of the maximum
      velocity. Thus, convection velocity can be determined in the presence of
      diffusion.

PMID- 11330981
TI  - Modeling the static fringe field of superconducting magnets.
AB  - The resonance frequency-space and the frequency gradient-space relations are
      evaluated analytically for the static fringe magnetic field of superconducting
      magnets used in the NMR diffusion measurements. The model takes into account the
      actual design of the high-homogeneity magnet coil system that consists of the
      main coil and the cryoshim coils and enables a precise calibration of the on-axis
      magnetic field gradient and the resonance frequency inside and outside of the
      superconducting coil.

PMID- 11330982
TI  - Sensitivity-enhanced static 15N NMR of solids by 1h indirect detection.
AB  - A method for enhancing the sensitivity of 15N spectra of nonspinning solids
      through 1H indirect detection is introduced. By sampling the 1H signals in the
      windows of a pulsed spin-lock sequence, high-sensitivity 1H spectra can be
      obtained in two-dimensional (2D) spectra whose indirect dimension yields the 15N
      chemical shift pattern. By sacrificing the 1H chemical shift information,
      sensitivity gains of 1.8 to 2.5 for the 15N spectra were achieved experimentally.
      A similar sensitivity enhancement was also obtained for 2D (15)N-(1)H dipolar and
      15N chemical shift correlation spectroscopy, by means of a 3D 1H/15N-1H/15N
      correlation experiment. We demonstrate this technique, termed PRINS for proton
      indirectly detected nitrogen static NMR, on a crystalline model compound with
      long 1H T(1rho) and on a 25-kDa protein with short 1H T(1rho). This 1H indirect
      detection approach should be useful for enhancing the sensitivity of 15N NMR of
      oriented membrane peptides. It can also be used to facilitate the empirical
      optimization of 15N-detected experiments where the inherent sensitivity of the
      sample is low.

PMID- 11330983
TI  - Macroscopic background gradient and radiation damping effects on high-field PGSE
      NMR diffusion measurements.
AB  - The effects of macroscopic background gradients due to susceptibility differences
      at the sample interfaces and of radiation damping on pulsed-gradient spin-echo
      (PGSE) experiments are examined. Both phenomena can lead to the seemingly strange
      effect of the echo signal growing as the gradient strength increases at low
      applied gradient strengths. For a freely diffusing species, background gradients
      manifest themselves as slight concave or convex inflections in the linearized
      PGSE attenuation curve, depending on the polarity of the applied gradient. The
      various means of overcoming macroscopic background gradient problems, including
      bipolar gradients, and their efficacy are examined experimentally and discussed.
      The effects of radiation damping can also result in the attenuation curve being
      nonlinear but, different from the effect of background gradients, the
      nonlinearity does not change with the polarity of the applied gradient. The
      vulnerability of the stimulated echo-based PGSE sequence and variations of Hahn
      based PGSE sequences is investigated. Both background gradients and radiation
      damping have serious implications for accurate diffusion measurement
      determination.

PMID- 11330984
TI  - Inverse detection and heteronuclear editing in 1H-15N correlation and 1H-1H
      double-quantum NMR spectroscopy in the solid state under fast MAS.
AB  - Signal enhancement in heteronuclear correlation spectra as well as signal
      selection in 1H experiments can be achieved through inverse, i.e., 1H, detection
      in the solid state under fast MAS conditions. Using recoupled polarization
      transfer (REPT), a heteronuclear 1H-15N single-quantum correlation (HSQC)
      experiment is presented whose symmetrical design allows the frequency dimensions
      to be easily interchanged. By observing the 15N dimension indirectly and
      detecting on 1H, the sensitivity is experimentally found to be increased by
      factors between 5 and 10 relative to conventional 15N detection. In addition, the
      inverse 1H-15N REPT-HSQC scheme can be readily used as a filter for the 1H
      signal. As an example, we present the combination of such a heteronuclear filter
      with a subsequent 1H-1H DQ experiment, yielding two-dimensional 15N-edited 1H-1H
      DQ MAS spectra. In this way, specific selection or suppression of 1H resonances
      is possible in solid-state MAS experiments, by use of which the resolution can be
      improved and information can be unravelled in 1H spectra.

PMID- 11330985
TI  - Enhanced sensitivity in RIACT/MQ-MAS NMR experiments using rotor assisted
      population transfer.
AB  - The rotor assisted population transfer (RAPT) sequence is used to enhance the
      sensitivity of the RIACT(II) experiment for spin-3/2 quadrupolar nuclei. A
      detailed theoretical analysis of the polarizations that contribute to different
      types of MQ-MAS experiments is provided. In particular, two polarization pathways
      are distinguished for the creation of triple-quantum coherence. The existence of
      these pathways is experimentally demonstrated by comparing the sensitivities of
      different sequences with and without RAPT preparation.

PMID- 11330986
TI  - Adiabatic dipolar recoupling in solid-state NMR: the DREAM scheme.
AB  - A theoretical treatment of the DREAM adiabatic homonuclear recoupling experiment
      is given using Floquet theory. An effective Hamiltonian is derived analytically
      and the time evolution of the density operator in the adiabatic limit is
      described. Shape cycles are proposed and characterized experimentally.
      Application to spin-pair filtering and as a mixing period in a 2D correlation
      experiment is explored and the experimental results are compared to theoretical
      predictions and exact numerical simulations.

PMID- 11330987
TI  - A sequential HNCA NMR pulse sequence for protein backbone assignment.
AB  - The conventional HNCA pulse sequence suffers from the ambiguity that it cannot
      distinguish inter- and intraresidue correlations because the one-bond and two
      bond J(NC(alpha)) coupling constants are of similar magnitude. This paper
      presents a novel pulse sequence, sequential HNCA, that leads to a spectrum
      exhibiting exclusively interresidue correlations. This important sequential
      information has so far usually been obtained by an HN(CO)CA experiment that for
      medium field strengths typically also is more sensitive than HNCA. However, for
      increasing static magnetic fields the chemical shift anisotropy relaxation
      mechanism of carbonyl carbons becomes more and more efficient, leading to a
      degradation of the HN(CO)CA sensitivity. Hence there is a point where the
      sequential HNCA experiment becomes the most sensitive option for sequential N
      C(alpha) correlation.

PMID- 11330988
TI  - Costs of occupational injuries and illnesses in California.
AB  - OBJECTIVES: The purpose of this study was to estimate the annual incidence, the
      mortality, and the direct and indirect costs associated with occupational
      injuries and illnesses in California in 1992. To achieve this, we performed
      aggregation and analysis of national and California data sets collected by the
      U.S. Bureau of Labor Statistics, California Workers' Compensation Insurance
      Rating Bureau, California Division of Industrial Relations, the National Center
      for Health Statistics, and the U.S. Health Care Financing Administration.
      METHODS: To assess incidence of and mortality from occupational injuries and
      illnesses, we reviewed data from state and national surveys and applied an
      attributable risk proportion method. To assess costs, we used the cost-of
      illness, human capital, method that decomposes costs into direct categories such
      as medical expenses and insurance administration expenses as well as indirect
      categories such as lost earnings, lost home production, and lost fringe benefits.
      Some cost estimates were drawn from California data, whereas others were drawn
      from a national study but were adjusted to reflect California's differences. Cost
      estimates for injuries were calculated by multiplying average costs by the number
      of injuries. For the majority of diseases, cost estimates relied on the
      attributable risk proportion method. RESULTS: Approximately 660 job-related
      deaths from injury, 1.645 million nonfatal injuries, 7,079 deaths from diseases,
      and 0.133 million illnesses are estimated to occur annually in the civilian
      California workforce. The direct ($7.04 billion, 34%) plus indirect ($13.62
      billion, 66%) costs were estimated to be $20.7 billion. Injuries cost $17.8
      billion (86%) and illnesses $2.9 billion (14%). These estimates are likely to be
      low because: (1) they ignore costs associated with pain and suffering, (2) they
      ignore home care provided by family members, and (3) the numbers of occupational
      injuries and illnesses are likely to be undercounted. CONCLUSION: Occupational
      injuries and illnesses are a major contributor to the total cost of health care
      and lost productivity in California. These costs are on a par with those of all
      cancers combined and only slightly less than the cost of heart disease and stroke
      in California. Workers' compensation covers less than one-half of the costs of
      occupational injury and illness.

PMID- 11330989
TI  - A message from Preventive Medicine and your physician: diabetes.

PMID- 11330990
TI  - Factors associated with self-reported pneumococcal immunization among adults 65
      years of age or older in the Minneapolis-St. Paul metropolitan area.
AB  - BACKGROUND: As part of a 3-year demonstration project to improve pneumococcal
      polysaccharide vaccine (PPV) coverage among older adults, the Minnesota
      Department of Health conducted a baseline evaluation of knowledge, attitudes, and
      beliefs among the general public regarding PPV. METHODS: A random-digit dialing
      telephone survey was conducted among community-dwelling adults age 65 years or
      older in three metropolitan counties in Minnesota during April through June 1998.
      RESULTS: Three hundred fifty-three interviews were completed; self-reported PPV
      coverage was 59% (95% CI 54%, 64%). Nearly all (94%) respondents reported at
      least one medical visit in the past year. Unvaccinated respondents expressed
      willingness to be vaccinated if they knew about PPV's safety, dosage, and
      preventive role. In a final multivariate regression model, factors associated
      with PPV vaccination included awareness of PPV (OR 7.8; CI 2.1, 29.2; P = 0.002),
      opinion that receiving PPV is "very important" (OR 8.3; CI 3.2, 21.6; P < 0.001),
      awareness that Medicare covers PPV (OR 5.1; CI 1.9, 13.8; P = 0.001), physician
      ever offering PPV (OR 21.7; CI 6.2, 76.6; P < 0.001), and physician regularly
      offering PPV (OR 3.9; CI 1.1, 13.7; P = 0.03). CONCLUSIONS: Respondents were
      significantly influenced by their physician offering PPV. Therefore, providers'
      practices are a critical target for improving PPV coverage. Educational efforts
      to inform patients about PPV and to address misconceptions (e.g., safety,
      efficacy, Medicare coverage) also may improve vaccination levels.

PMID- 11330991
TI  - Health effect of improved meal ambiance in a Dutch nursing home: a 1-year
      intervention study.
AB  - BACKGROUND: The aim of this study was to determine the effect of an improved
      ambiance of food consumption on health and nutritional status of Dutch nursing
      home elderly residents (n = 38) in a 1-year intervention study. METHODS: A
      parallel group intervention study was performed. Improvement of ambiance focused
      on three points: (1) physical environment and atmosphere of the dining room, (2)
      food service, (3) organization of the nursing staff assistance. Dietary intake,
      biochemical indicators of nutritional and health status and quality of life
      (Sickness Impact Profile and Philadelphia Geriatric Center Moral Scale) were
      assessed at baseline and after 1 year of intervention. Body weight, used as an
      indicator of compliance and nutritional status, was assessed every 4 months.
      RESULTS: Twenty-two subjects completed the 1-year intervention trial. Mean body
      weight significantly increased (+3.3 kg, P < 0.05) in the experimental group (n =
      12), not in the control group (-0.4 kg, P = 0.78; n = 10). Health status
      biochemical indicators and the SIP score remained stable in the experimental
      group, indicating relatively stable health conditions. On the contrary, negative
      changes in the control group suggested a decline in health status. Dietary
      intake, which was insufficient at baseline, increased in both groups.
      CONCLUSIONS: This study showed that improving the ambiance of food consumption is
      a non-negligible issue for improving nutritional status and stabilizing health of
      nursing home residents.

PMID- 11330992
TI  - Prevalence of serological markers against measles, rubella, varicella, hepatitis
      B, hepatitis C, and human immunodeficiency virus among medical residents in
      Mexico.
AB  - BACKGROUND: Vaccination programs among health care workers are based on
      seroprevalence studies, which seldom include medical residents or students. The
      objective of this study was to determine the seroprevalence of antibodies against
      measles, rubella, varicella, hepatitis B (HBV), hepatitis C (HCV), and human
      immunodeficiency virus (HIV) among medical residents. METHODS: This study was
      designed as a prospective survey. A self-reported questionnaire was used to
      obtain the information. Serum samples were tested for antibodies by commercial
      immunoenzymatic assays. Statistical analysis was descriptive; history of exposure
      was evaluated as a diagnostic test and sensitivity, specificity, and predictive
      values were calculated according to Bayes theorem. RESULTS: Eighty-nine residents
      were included, the median age was 27 years, and 58 (65.2%) were female. Seventy
      two (79.7%) had been vaccinated against HBV, but vaccination was complete in only
      30/72 (41.6%). All were positive for measles and varicella, with the exception of
      one case for each. The serology for rubella was negative in 12 residents (10
      women). Three residents had anti-core against HBV, with negative surface antigen.
      One positive case for HCV was confirmed by Western blot. All were negative for
      HIV. A history of prior varicella had a 100% positive predictive value; in
      contrast, the negative predictive value was quite low (7%). CONCLUSIONS: Negative
      serology for rubella among women and incomplete vaccination against HBV support
      the implementation of vaccination programs in medical schools in Mexico.

PMID- 11330993
TI  - Obesity is associated with reduced self-rated general health status: evidence
      from a representative sample of white, black, and Hispanic Americans.
AB  - BACKGROUND: Although the evidence linking obesity with many chronic diseases is
      well established, the relationship with self-rated health is not clear. Self
      rating of health is a broad summary measure of different domains of health that
      include psychosocial domain. The aims of this study were to examine the
      relationship between obesity and self-rated health and the degree of agreement
      between patients' self-rated health status and physicians' impression of
      patients' health in a representative sample of healthy noninstitutionalized
      American adults. METHODS: Data (n = 10, 298) used for this analysis were obtained
      from the Third National Health and Nutrition Examination Survey. Normal weight
      was defined as BMI 18.5-24.9 kg/m(2) and preobesity was defined as BMI 25-29.9
      kg/m(2). Moderate (class I) obesity was defined as BMI 30-34.9 kg/m(2) and severe
      (class II) obesity as BMI > or =35 kg/m(2). Self-rated health conditions were
      categorized as excellent, very good, good, fair, or poor. Agreement between
      physicians' impression and self-rated health and a linear relationship between
      obesity and individual perceived health were quantified using kappa and gamma
      statistics, respectively. Using the logistic regression analysis, odds of
      reporting reduced health in preobese, class I obese, and class II obese
      individuals were compared with those for normal-weight individuals, adjusting for
      age, current smoking, and alcohol intake. The contribution of obesity to ethnic
      differences in reduced self-rated health was determined by comparing blacks with
      whites and Hispanics with whites fitted in multiple logistic regression models.
      RESULTS: Among both men and women, there was a statistically significant linear
      association between obesity and self-rated health (P < 0.05). The proportion of
      subjects reporting excellent health tended to decrease with increasing level of
      obesity in the three ethnic groups. In the three ethnic groups, the degrees of
      concordance between self-rated health and physicians' impressions were poor and
      decreased with increasing obesity level. In each ethnic group, class II obesity
      was associated with approximately twofold increased odds of reporting reduced
      health compared with normal-weight individuals. Compared to whites, black and
      Hispanic races/ethnicities were respectively associated with 23 and 175%
      increased odds of reduced self-rated health among men. The corresponding values
      for women were 45 and 177%, respectively. CONCLUSION: The results of this study
      provide evidence that obesity has a negative impact on self-rated health among
      adults, even in the absence of chronic disease conditions. The results of this
      investigation also underscore the need to craft national preventive strategies to
      curb obesity in these at-risk population groups.

PMID- 11330994
TI  - Hazard of smoking initiation by age among adolescents in Wuhan, China.
AB  - BACKGROUND: Knowledge about age of smoking initiation among adolescents in China
      is helpful for exploring cultural differences in adolescent smoking behavior and
      informative for global tobacco control. However, little has been documented on
      this issue. METHOD: Adolescents (6,473) attending grades 7, 8, and 9 completed
      the baseline survey of a longitudinal, randomized smoking prevention trial. Data
      were collected in classrooms with a paper-and-pencil questionnaire. A survival
      model was used in the statistical analysis. RESULTS: The hazard of smoking
      initiation for boys showed a pattern previously observed in the United States:
      very low (<2%) before 7 years of age, increasing rapidly after age 10, and
      peaking at 14-15 years of age. The hazard for girls was below or around 1% until
      12 years of age before it increased. The hazard levels were similar for
      adolescents both in urban and in rural areas, but higher for those in grade 7
      than in grades 8 and 9. CONCLUSIONS: Chinese boys in Wuhan, China, experienced a
      hazard pattern of smoking initiation by age similar to those observed in the
      United States, while Chinese girls there experienced a rather low risk of smoking
      initiation. The hazard pattern suggests that the best time for smoking prevention
      is between 10 and 15 years of age. Adolescents in lower grades are at higher risk
      of early smoking initiation, suggesting a potential cohort effect in adolescent
      smoking initiation in Wuhan, China.

PMID- 11330995
TI  - Kinetic analysis of three activated phenylalanyl intermediates generated by the
      initiation module PheATE of gramicidin S synthetase.
AB  - The three-domain initiation module PheATE (GrsA) of Bacillus brevis gramicidin S
      synthetase catalyzes the activation, thiolation and epimerization of L
      phenylalanine (L-Phe), the first amino acid incorporated into the decapeptide
      antibiotic gramicidin S. There are three activated intermediates in the PheATE
      catalyzed chemical pathway: L-phenylalanyl-adenosine-5'-monophosphate diester (L
      Phe-AMP), L-Phe-S-4'-phosphopantetheine(Ppant)- and D-Phe-S-4'-Ppant-acyl enzyme.
      In this study, we examined PheATE in single-turnover catalysis using rapid
      chemical quench techniques. Kinetic modeling of the process of disappearance of
      the substrate L-Phe, transient appearance and disappearance of L-Phe-AMP and the
      ad seriatim formation and equilibration of the L- and D-Phe-S-Ppant-acyl enzyme
      adducts allowed evaluation of the microscopic rate constants for the three
      chemical reactions in the initiation module PheATE. This study provides the first
      transient-state kinetic analysis of a nonribosomal peptide synthetase (NRPS)
      module.

PMID- 11330996
TI  - Thermodynamics of metal ion binding. 1. Metal ion binding by wild-type carbonic
      anhydrase.
AB  - Understanding the energetic consequences of molecular structure in aqueous
      solution is a prerequisite to the rational design of synthetic motifs with
      predictable properties. Such properties include ligand binding and the collapse
      of polymer chains into discrete three-dimensional structures. Despite advances in
      macromolecular structure determination, correlations of structure with high
      resolution thermodynamic data remain limited. Here we compare thermodynamic
      parameters for the binding of Zn(II), Cu(II), and Co(II) to human carbonic
      anhydrase II. These calorimetrically determined values are interpreted in terms
      of high-resolution X-ray crystallographic data. While both zinc and cobalt are
      bound with a 1:1 stoichiometry, CAII binds two copper ions. Considering only the
      high-affinity site, there is a diminution in the enthalpy of binding through the
      series Co(II) --> Zn(II) --> Cu(II) that mirrors the enthalpy of hydration; this
      observation reinforces the notion that the thermodynamics of solute association
      with water is at least as important as the thermodynamics of solute-solute
      interaction and that these effects must be considered when interpreting
      association in aqueous solution. Additionally, DeltaC(p) data suggest that zinc
      binding to CAII proceeds with a greater contribution from desolvation than does
      binding of either copper or cobalt, suggesting Nature optimizes binding by
      optimizing desolvation.

PMID- 11330997
TI  - Thermodynamics of metal ion binding. 2. Metal ion binding by carbonic anhydrase
      variants.
AB  - The ability to construct molecular motifs with predictable properties in aqueous
      solution requires an extensive knowledge of the relationships between structure
      and energetics. The design of metal binding motifs is currently an area of
      intense interest in the bioorganic community. To date synthetic motifs designed
      to bind metal ions lack the remarkable affinities observed in biological systems.
      To better understand the structural basis of metal ion affinity, we report here
      the thermodynamics of binding of divalent zinc ions to wild-type and mutant
      carbonic anhydrases and the interpretation of these parameters in terms of
      structure. Mutations were made both to the direct His ligand at position 94 and
      to indirect, or second-shell, ligands Gln-92, Glu-117, and Thr-199. The
      thermodynamics of ligand binding by several mutant proteins is complicated by the
      development of a second zinc binding site on mutation; such effects must be
      considered carefully in the interpretation of thermodynamic data. In all
      instances modification of the protein produces a complex series of changes in
      both the enthalpy and entropy of ligand binding. In most cases these effects are
      most readily rationalized in terms of ligand and protein desolvation, rather than
      in terms of changes in the direct interactions of ligand and protein. Alteration
      of second-shell ligands, thought to function primarily by orienting the direct
      ligands, produces profoundly different effects on the enthalpy of binding,
      depending on the nature of the residue. These results suggest a range of
      activities for these ligands, contributing both enthalpic and entropic effects to
      the overall thermodynamics of binding. Together, our results demonstrate the
      importance of understanding relationships between structure and hydration in the
      construction of novel ligands and biological polymers.

PMID- 11330998
TI  - Organization of the multiple coenzymes and subunits and role of the covalent
      flavin link in the complex heterotetrameric sarcosine oxidase.
AB  - Heterotetrameric (alphabetagammadelta) sarcosine oxidase from Corynebacterium sp.
      P-1 (cTSOX) contains noncovalently bound FAD and NAD(+) and covalently bound FMN,
      attached to beta(His173). The beta(His173Asn) mutant is expressed as a
      catalytically inactive, labile heterotetramer. The beta and delta subunits are
      lost during mutant enzyme purification, which yields a stable alphagamma complex.
      Addition of stabilizing agents prevents loss of the delta but not the beta
      subunit. The covalent flavin link is clearly a critical structural element and
      essential for TSOX activity or preventing FMN loss. The alpha subunit was
      expressed by itself and purified by affinity chromatography. The alpha and beta
      subunits each contain an NH(2)-terminal ADP-binding motif that could serve as
      part of the binding site for NAD(+) or FAD. The alpha subunit and the alphagamma
      complex were each found to contain 1 mol of NAD(+) but no FAD. Since NAD(+) binds
      to alpha, FAD probably binds to beta. The latter could not be directly
      demonstrated since it was not possible to express beta by itself. However, FAD in
      TSOX from Pseudomonas maltophilia (pTSOX) exhibits properties similar to those
      observed for the covalently bound FAD in monomeric sarcosine oxidase and N
      methyltryptophan oxidase, enzymes that exhibit sequence homology with beta. A
      highly conserved glycine in the ADP-binding motif of the alpha(Gly139) or
      beta(Gly30) subunit was mutated in an attempt to generate NAD(+)- or FAD-free
      cTSOX, respectively. The alpha(Gly139Ala) mutant is expressed only at low
      temperature (t(optimum) = 15 degrees C), but the purified enzyme exhibited
      properties indistinguishable from the wild-type enzyme. The much larger barrier
      to NAD(+) binding in the case of the alpha(Gly139Val) mutant could not be
      overcome even by growth at 3 degrees C, suggesting that NAD(+) binding is
      required for TSOX expression. The beta(Gly30Ala) mutant exhibited subunit
      expression levels similar to those of the wild-type enzyme, but the mutation
      blocked subunit assembly and covalent attachment of FMN, suggesting that both
      processes require a conformational change in beta that is induced upon FAD
      binding. About half of the covalent FMN in recombinant preparations of cTSOX or
      pTSOX is present as a reversible covalent 4a-adduct with a cysteine residue.
      Adduct formation is not prevented by mutating any of the three cysteine residues
      in the beta subunit of cTSOX to Ser or Ala. Since FMN is attached via its 8
      methyl group to the beta subunit, the FMN ring must be located at the interface
      between beta and another subunit that contains the reactive cysteine residue.

PMID- 11330999
TI  - Insight into the catalytic mechanism of DNA polymerase beta: structures of
      intermediate complexes.
AB  - The catalytic reaction mediated by DNA polymerases is known to require two Mg(II)
      ions, one associated with dNTP binding and the other involved in metal ion
      catalysis of the chemical step. Here we report a functional intermediate
      structure of a DNA polymerase with only one metal ion bound, the DNA polymerase
      beta-DNA template-primer-chromium(III).2'-deoxythymidine 5'-beta,gamma
      methylenetriphosphate [Cr(III).dTMPPCP] complex, at 2.6 A resolution. The complex
      is distinct from the structures of other polymerase-DNA-ddNTP complexes in that
      the 3'-terminus of the primer has a free hydroxyl group. Hence, this structure
      represents a fully functional intermediate state. Support for this contention is
      provided by the observation of turnover in biochemical assays of crystallized
      protein as well as from the determination that soaking Pol beta crystals with
      Mn(II) ions leads to formation of the product complex, Pol beta-DNA-Cr(III).PCP,
      whose structure is also reported. An important feature of both structures is that
      the fingers subdomain is closed, similar to structures of other ternary complexes
      in which both metal ion sites are occupied. These results suggest that closing of
      the fingers subdomain is induced specifically by binding of the metal-dNTP
      complex prior to binding of the catalytic Mg(2+) ion. This has led us to
      reevaluate our previous evidence regarding the existence of a rate-limiting
      conformational change in Pol beta's reaction pathway. The results of stopped-flow
      studies suggest that there is no detectable rate-limiting conformational change
      step.

PMID- 11331000
TI  - A conserved threonine within Escherichia coli leucyl-tRNA synthetase prevents
      hydrolytic editing of leucyl-tRNALeu.
AB  - Aminoacyl-tRNA synthetases ensure the fidelity of protein synthesis by accurately
      selecting and activating cognate amino acids for aminoacylation of the correct
      tRNA. Some tRNA synthetases have evolved an editing active site that is separate
      from the amino acid activation site providing two steps or "sieves" for amino
      acid selection. These two sieves rely on different strategies for amino acid
      recognition to significantly enhance the accuracy of aminoacylation. We have
      performed alanine scanning mutagenesis in a conserved threonine-rich region of
      the Escherichia coli leucyl-tRNA synthetase's CP1 domain that is hypothesized to
      contain a putative editing active site. Characterization of purified mutant
      proteins led to the identification of a single conserved threonine that prevents
      the cognate leucine amino acid from being hydrolyzed after aminoacylation of the
      tRNA. Mutation of this threonine to an alanine eliminates discrimination of the
      cognate amino acid in the editing active site. This provides a molecular example
      of an amino acid discrimination mechanism in the tRNA synthetase's editing active
      site.

PMID- 11331001
TI  - Biosynthesis of L-selectin ligands: sulfation of sialyl Lewis x-related
      oligosaccharides by a family of GlcNAc-6-sulfotransferases.
AB  - The leukocyte adhesion molecule L-selectin mediates lymphocyte homing to
      secondary lymphoid organs and to certain sites of inflammation. The cognate
      ligands for L-selectin possess the unusual sulfated tetrasaccharide epitope 6
      sulfo sialyl Lewis x (Siaalpha2-->3Galbeta1-->4[Fucalpha1-->3][SO(3)-->6]GlcNAc).
      Sulfation of GlcNAc within sialyl Lewis x is a crucial modification for L
      selectin binding, and thus, the underlying sulfotransferase may be a key
      modulator of lymphocyte trafficking. Four recently discovered GlcNAc-6
      sulfotransferases are the first candidate contributors to the biosynthesis of 6
      sulfo sLex in the context of L-selectin ligands. Here we report the in vitro
      activity of the four GlcNAc-6-sulfotransferases on a panel of synthetic
      oligosaccharide substrates that comprise structural motifs derived from sialyl
      Lewis x. Each enzyme preferred a terminal GlcNAc residue, and was impeded by the
      addition of a beta1,4-linked Gal residue (i.e., terminal LacNAc). Surprisingly,
      for three of the enzymes, significant activity was observed with sialylated
      LacNAc, and two of the enzymes were capable of detectable sulfation of GlcNAc in
      the context of sialyl Lewis x. On the basis of these results, we propose possible
      pathways for 6-sulfo sialyl Lewis x biosynthesis and suggest that sulfation may
      be an early committed step.

PMID- 11331002
TI  - Mutations of the asparagine117 residue of a receptor activity-modifying protein 1
      dependent human calcitonin gene-related peptide receptor result in selective loss
      of function.
AB  - The initially orphan human calcitonin (CT) receptor-like receptor (hCRLR)
      interacts with novel accessory receptor activity-modifying protein 1 (RAMP1) to
      reveal a functional CT gene-related peptide (CGRP) receptor. In mammalian cells,
      RAMP1 is required for mature N-glycosylation of the hCRLR predicted to occur at
      Asn(60), Asn(112), and/or Asn(117) in the amino-terminal extracellular domain.
      Here we have shown that the substitution of Asn(117) with Ala, Gln, Thr, or Pro
      abolished CGRP-evoked cAMP formation which was left unchanged when the Asn(117)
      was replaced with Asp. Moreover, the hCRLR and the Asn(117) mutants exhibited
      comparable N-glycosylation and cell surface expression, and the association with
      RAMP1 was only slightly impaired. In contrast, the hCRLR Asn(60,112) to Thr
      double mutant exhibited defective RAMP1-dependent N-glycosylation, and impaired
      cell surface expression and CGRP receptor function. Unlike Asn(60) and Asn(112),
      Asn(117) is normally not N-glycosylated, but essential for CGRP binding to the
      hCRLR-RAMP1 complex.

PMID- 11331003
TI  - Crystallographic studies on endothelial nitric oxide synthase complexed with
      nitric oxide and mechanism-based inhibitors.
AB  - The crystal structure of the endothelial nitric oxide synthase (NOS) heme domain
      complexed with NO reveals close hydrogen bonding interactions between NO and the
      terminal guanidino nitrogen of the substrate, L-arginine. Dioxygen is expected to
      bind in a similar mode which will facilitate proton abstraction from L-Arg to
      dioxygen, a required step for O-O bond cleavage. Structures of mechanism-based
      NOS inhibitors, N(5)-(1-iminoethyl)-L-ornithine and N-(3
      (aminomethyl)benzyl)acetamidine, provide clues on how this class of compounds
      operate as suicide substrate inhibitors leading to heme oxidation.

PMID- 11331004
TI  - The crystal structure of a fusagenic sperm protein reveals extreme surface
      properties.
AB  - Sp18 is an 18 kDa protein that is released from abalone sperm during the acrosome
      reaction. It coats the acrosomal process where it is thought to mediate fusion
      between sperm and egg cell membranes. Sp18 is evolutionarily related to lysin, a
      16 kDa abalone sperm protein that dissolves the vitelline envelope surrounding
      the egg. The two proteins were generated by gene duplication followed by rapid
      divergence by positive selection. Here, we present the crystal structure of green
      abalone sp18 resolved to 1.86 A. Sp18 is composed of a bundle of five alpha
      helices with surface clusters of basic and hydrophobic residues, giving it a
      large dipole moment and making it extremely amphipathic. The large clusters of
      hydrophobic surface residues and domains of high positive electrostatic surface
      charge explain sp18's ability as a potent fusagen of liposomes. The overall fold
      of sp18 is similar to that of green abalone lysin; however, the surface features
      of the proteins are quite different, accounting for their different roles in
      fertilization. This is the first crystal structure of a protein implicated in
      sperm-egg fusion during animal fertilization.

PMID- 11331005
TI  - NMR structure of human apolipoprotein C-II in the presence of sodium dodecyl
      sulfate.
AB  - The structure and protein-detergent interactions of apolipoprotein C-II (apoC-II)
      in the presence of SDS micelles have been investigated using circular dichroism
      and heteronuclear NMR techniques applied to (15)N-labeled protein. Micellar SDS,
      a commonly used mimetic of the lipoprotein surface, inhibits the aggregation of
      apoC-II and induces a stable structure containing approximately 60% alpha-helix
      as determined by circular dichroism. NMR reveals the first 12 residues of apoC-II
      to be structurally heterogeneous and largely disordered, with the rest of the
      protein forming a predominantly helical structure. Three regions of helical
      conformation, residues 16-36, 50-56, and 63-77, are well-defined by NMR-derived
      constraints, with the intervening regions showing more loosely defined helical
      conformation. The structure of apoC-II is compared to that determined for other
      apolipoproteins in a similar environment. Our results shed light on the lipid
      interactions of apoC-II and its mechanism of lipoprotein lipase activation.

PMID- 11331006
TI  - Involvement of the Arg-Asp-His catalytic triad in enzymatic cleavage of the
      phosphodiester bond.
AB  - Phosphatidylinositol-specific phospholipase C (PI-PLC) catalyzes the cleavage of
      the P-O bond in phosphatidylinositol via intramolecular nucleophilic attack of
      the 2-hydroxyl group of inositol on the phosphorus atom. Our earlier
      stereochemical and site-directed mutagenesis studies indicated that this reaction
      proceeds by a mechanism similar to that of RNase A, and that the catalytic site
      of PI-PLC consists of three major components analogous to those observed in RNase
      A, the His32 general base, the His82 general acid, and Arg69 acting as a
      phosphate-activating residue. In addition, His32 is associated with Asp274 in
      forming a catalytic triad with inositol 2-hydroxyl, and His82 is associated with
      Asp33 in forming a catalytic diad. The focus of this work is to provide a global
      view of the mechanism, assess cooperation between various catalytic residues, and
      determine the origin of enzyme activation by the hydrophobic leaving group. To
      this end, we have investigated kinetic properties of Arg69, Asp33, and His82
      mutants with phosphorothioate substrate analogues which feature leaving groups of
      varying hydrophobicity and pK(a). Our results indicate that interaction of the
      nonbridging pro-S oxygen atom of the phosphate group with Arg69 is strongly
      affected by Asp33, and to a smaller extent by His82. This result in conjunction
      with those obtained earlier can be rationalized in terms of a novel, dual
      function triad comprised of Arg69, Asp33, and His82 residues. The function of
      this triad is to both activate the phosphate group toward the nucleophilic attack
      and to protonate the leaving group. In addition, Asp33 and His82 mutants
      displayed much smaller degrees of activation by the fatty acid-containing leaving
      group as compared to the wild-type (WT) enzyme, and the level of activation was
      significantly reduced for substrates featuring the leaving group with low pK(a)
      values. These results strongly suggest that the assembly of the above three
      residues into the fully catalytically competent triad is controlled by the
      hydrophobic interactions of the enzyme with the substrate leaving group.

PMID- 11331007
TI  - Mechanism of phosphatidylinositol-specific phospholipase C: origin of unusually
      high nonbridging thio effects.
AB  - Phosphatidylinositol-specific phospholipase C (PI-PLC) has been proposed
      previously to employ a catalytic mechanism highly reminiscent of that of
      ribonuclease A (RNase A). Both catalytic sites are comprised of two histidine
      side chains acting as a general base-general acid pair and a phosphate-activating
      residue: an arginine in the case of PI-PLC and a lysine in RNase A. Despite these
      structural similarities, the PI-PLC reaction is slowed 10(5)-fold upon
      substitution of one of the phosphate nonbridging oxygen atoms with sulfur,
      whereas a much smaller effect is observed in the analogous RNase A reaction.
      Here, we report a systematic study of this property in PI-PLC, conducted by means
      of site-directed chemical modification of a cysteine residue replacing the
      arginine at position 69. The results show that mutant enzymes featuring bidentate
      side chains at this position display significantly higher activity, higher thio
      effects, and greater stereoselectivity than do those with monodentate side
      chains. The results suggest that the bidentate nature of Arg69 is the origin of
      the large thio effects and stereoselectivity in PI-PLC. We propose that in
      addition to binding the phosphate, the function of arginine 69 is to bring the
      phosphate group and the 2-OH group of inositol into proximity and to induce
      proper alignment for nucleophilic attack, and possibly to lower the pK(a) of the
      2-OH. The results presented here could be important to mechanisms of phosphoryl
      transfer enzymes in general, suggesting that a major part of thio effects
      observed in enzymatic phosphoryl transfer reactions can originate from factors
      other than direct interaction between a side chain and a phosphate group, and
      caution the use of the absolute magnitude of the thio effect as an indicator of
      the strength of such interactions.

PMID- 11331008
TI  - Identification of the 6-sulfate binding site unique to alpha-subunit-containing
      isozymes of human beta-hexosaminidase.
AB  - In humans, beta-hexosaminidase A (alphabeta) is required to hydrolyze GM2
      ganglioside. A deficiency of either the alpha- or beta-subunit leads to a severe
      neurological disease, Tay-Sachs or Sandhoff disease, respectively. In mammals
      beta-hexosaminidase B (betabeta) and S (alphaalpha) are other major and minor
      isozymes. The primary structures of the alpha- and beta-subunits are 60%
      identical, but only the alpha-containing isozymes can efficiently hydrolyze beta
      linked GlcNAc-6-SO(4) from natural or artificial substrates. Hexosaminidase has
      been grouped with glycosidases in family 20. A molecular model of the active site
      of the human hexosaminidase has been generated from the crystal structure of a
      family 20 bacterial chitobiase. We now use the chitobiase structure to identify
      residues close to the carbon-6 oxygen of NAG-A, the nonreducing beta-GlcNAc
      residue of its bound substrate. The chitobiase side chains in the best
      interactive positions align with alpha-Asn(423)Arg(424) and beta
      Asp(453)Leu(454). The change in charge from positive in alpha to negative in beta
      is consistent with the lower K(m) of hexosaminidase S, and the much higher K(m)
      and lower pH optimum of hexosaminidase B, toward sulfated versus unsulfated
      substrates. In vitro mutagenesis, CHO cell expression, and kinetic analyses of an
      alphaArg(424)Lys hexosaminidase S detected little change in V(max) but a 2-fold
      increase in K(m) for the sulfated substrate. Its K(m) for the nonsulfated
      substrate was unaffected. When alphaAsn(423) was converted to Asp, again only the
      K(m) for the sulfated substrate was changed, increasing by 6-fold. Neutralization
      of the charge on alphaArg(424) by substituting Gln produced a hexosaminidase S
      with a K(m) decrease of 3-fold and a V(max) increased by 6-fold for the
      unsulfated substrate, parameters nearly identical to those of hexosaminidase B at
      pH 4.2. As well, for the sulfated substrate at pH 4.2 its K(m) was increased 9
      fold and its V(max) decreased 1.5-fold, values very similar to those of
      hexosaminidase B obtained at pH 3.0, where its betaAsp(453) becomes protonated.

PMID- 11331009
TI  - Spectrometric evidence for the flavin-1-phenylcyclopropylamine inactivator adduct
      with monoamine oxidase N.
AB  - 1-Phenylcyclopropylamine (1-PCPA) is shown to be an inactivator of the fungal
      flavoenzyme monoamine oxidase (MAO) N. Inactivation results in an increase in
      absorbance at 410 nm and is accompanied by the concomitant loss of the flavin
      absorption band at 458 nm. The spectral properties of the covalent adduct formed
      between the flavin cofactor of MAO N and 1-PCPA are similar to those reported for
      the irreversible inactivation product formed with 1-PCPA and mammalian
      mitochondrial monoamine oxidase B [Silverman, R. B., and Zieske, P. A. (1985)
      Biochemistry 24, 2128-2138]. There is a hypsochromic shift of the 410 nm band
      upon lowering the pH to 2, indicating that an N(5)-flavin adduct formed upon
      inactivation. Use of the fungal enzyme, MAO N, which lacks the covalent
      attachment to the flavin adenine dinucleotide (FAD) cofactor present in the
      mammalian forms MAO A and MAO B, has allowed for the isolation and further
      structural identification of the flavin-inactivator adduct. The incorporation of
      two (13)C labels into the inactivator, [2,3-(13)C(2)]-1-PCPA, followed by
      analysis using on-line liquid chromatography/electrospray ionization mass
      spectrometry and nuclear magnetic resonance spectroscopy, provided a means to
      explore the structure of the flavin-inactivator adduct of MAO N. The spectral
      evidence supports covalent attachment of the 1-PCPA inactivator to the cofactor
      as N(5)-3-oxo-3-phenylpropyl-FAD.

PMID- 11331010
TI  - Study of the conformational transition of A beta(1-42) using D-amino acid
      replacement analogues.
AB  - A critical event in Alzheimer's disease is the transition of Abeta peptides from
      their soluble forms into disease-associated beta-sheet-rich conformers.
      Structural analysis of a complete D-amino acid replacement set of Abeta(1-42)
      enabled us to localize in the full-length 42-mer peptide the region responsible
      for the conformational switch into a beta-sheet structure. Although NMR
      spectroscopy of trifluoroethanol-stabilized monomeric Abeta(1-42) delineated two
      separated helical domains, only the destabilization of helix I, comprising
      residues 11-24, caused a transition to a beta-sheet structure. This
      conformational alpha-to-beta switch was directly accompanied by an aggregation
      process leading to the formation of amyloid fibrils.

PMID- 11331011
TI  - NMR mapping and secondary structure determination of the major acetylcholine
      receptor alpha-subunit determinant interacting with alpha-bungarotoxin.
AB  - The alpha-subunit of the nicotinic acetylcholine receptor (alphaAChR) contains a
      binding site for alpha-bungarotoxin (alpha-BTX), a snake-venom-derived alpha
      neurotoxin. Previous studies have established that the segment comprising
      residues 173-204 of alphaAChR contains the major determinant interacting with the
      toxin, but the precise boundaries of this determinant have not been clearly
      defined to date. In this study, we applied NMR dynamic filtering to determine the
      exact sequence constituting the major alphaAChR determinant interacting with
      alpha-BTX. Two overlapping synthetic peptides corresponding to segments 179-200
      and 182-202 of the alphaAChR were complexed with alpha-BTX. HOHAHA and ROESY
      spectra of these complexes acquired with long mixing times highlight the residues
      of the peptide that do not interact with the toxin and retain considerable
      mobility upon binding to alpha-BTX. These results, together with changes in the
      chemical shifts of the peptide protons upon complex formation, suggest that
      residues 184-200 form the contact region. At pH 4, the molecular mass of the
      complex determined by dynamic light scattering (DLS) was found to be 11.2 kDa, in
      excellent agreement with the expected molecular mass of a 1:1 complex, while at
      pH >5 the DLS measurement of 20 kDa molecular mass indicated dimerization of the
      complex. These results were supported by T(2) measurements. Complete resonance
      assignment of the 11.2 kDa complex of alpha-BTX bound to the alphaAChR peptide
      comprising residues 182-202 was obtained at pH 4 using homonuclear 2D NMR spectra
      measured at 800 MHz. The secondary structures of both alpha-BTX and the bound
      alphaAChR peptide were determined using 2D (1)H NMR experiments. The peptide
      folds into a beta-hairpin conformation, in which residues (R)H186-(R)V188 and
      (R)Y198-(R)D200 form the two beta-strands. Residues (R)Y189-(R)T191 form an
      intermolecular beta-sheet with residues (B)K38-(B)V40 of the second finger of
      alpha-BTX. These results accurately pinpoint the alpha-BTX-binding site on the
      alphaAChR and pave the way to structure determination of this important alphaAChR
      determinant involved in binding acetylcholine and cholinergic agonists and
      antagonists.

PMID- 11331012
TI  - Proof of principle in a de novo designed protein maquette: an allosterically
      regulated, charge-activated conformational switch in a tetra-alpha-helix bundle.
AB  - New understanding of the engineering and allosteric regulation of natural protein
      conformational switches (such as those that couple chemical and ionic signals,
      mechanical force, and electro/chemical free energy for biochemical activation,
      catalysis, and motion) can be derived from simple de novo designed synthetic
      protein models (maquettes). We demonstrate proof of principle of both reversible
      switch action and allosteric regulation in a tetra-alpha-helical bundle protein
      composed of two identical di-helical subunits containing heme coordinated at a
      specific position close to the disulfide loop region. Individual bundles assume
      one of two switch states related by large-scale mechanical changes: a syn
      topology (helices of the different subunits parallel) or anti-topology (helices
      antiparallel). Both the spectral properties of a coproporphyrin probe appended to
      the loop region and the distance-dependent redox interaction between the hemes
      identify the topologies. Beginning from a syn-topology, introduction of ferric
      heme in each subunit (either binding or redox change) shifts the topological
      balance by 25-50-fold (1.9-2.3 kcal/mol) to an anti-dominance. Charge repulsion
      between the two internal cationic ferric hemes drives the syn- to anti-switch, as
      demonstrated in two ways. When fixed in the syn-topology, the second ferric heme
      binding is 25-80-fold (1.9-2.6 kcal/mol) weaker than the first, and adjacent heme
      redox potentials are split by 80 mV (1.85 kcal/mol), values that energetically
      match the shift in topological balance. Allosteric and cooperative regulation of
      the switch by ionic strength exploits the shielded charge interactions between
      the two hemes and the exposed, cooperative interactions between the
      coproporphyrin carboxylates.

PMID- 11331013
TI  - Stability and global fold of the mouse prohormone convertase 1 pro-domain.
AB  - We have purified the mouse prohormone convertase 1 (PC1) pro-domain expressed in
      Escherichia coli cells and demonstrated, using a number of biophysical methods,
      that this domain is an independent folding unit with a T(m) of 39 degrees C at a
      protein concentration of 20 microM and pH 7.0. This differs significantly from
      similar pro-domains in bacteria and human furin, which are unfolded at 25 degrees
      C and require the catalytic domain in order to be structured [Bryan et al. (1995)
      Biochemistry 34, 10310-10318; Bhattacharjya et al. (2000) J. Biomol. NMR 16, 275
      276]. Using heteronuclear NMR spectroscopy, we have determined the backbone (1)H,
      (13)C, and (15)N assignments for the pro-domain of PC1. On the basis of
      (1)H/(13)C chemical shift indices, NOE analysis, and hydrogen exchange
      measurements, the pro-domain is shown to consist of a four-stranded beta-sheet
      and two alpha-helices. The results presented here show that both the bacterial
      pro-domain in complex with subtilisin and the uncomplexed mouse PC1 pro-domain
      have very similar overall folds despite a lack of sequence homology. The
      structural data help to explain the location of the secondary processing sites in
      the pro-domains of the PC family, and a consensus sequence for binding to the
      catalytic domain is proposed.

PMID- 11331014
TI  - Evidence that apolipoprotein A-I facilitates hepatic lipase-mediated phospholipid
      hydrolysis in reconstituted HDL containing apolipoprotein A-II.
AB  - This study examines hepatic lipase (HL) mediated phospholipid hydrolysis in
      mixtures of apolipoprotein-specific, spherical reconstituted high-density
      lipoproteins (rHDL). We have shown previously that apolipoprotein A-I (apoA-I)
      and apoA-II have a major influence on the kinetics of HL-mediated phospholipid
      and triacylglycerol hydrolysis in well-characterized, homogeneous preparations of
      spherical rHDL [Hime, N. J., Barter, P. J., and Rye, K.-A. (1998) J. Biol. Chem.
      273, 27191-27198]. In the present study, phospholipid hydrolysis was assessed in
      mixtures of rHDL containing either apoA-I only, (A-I)rHDL, apoA-II only, (A
      II)rHDL, or both apoA-I and apoA-II, (A-I/A-II)rHDL. The rHDL contained trace
      amounts of radiolabeled phospholipid, and hydrolysis was measured as the
      formation of radiolabeled nonesterified fatty acids (NEFA). As predicted from our
      previous kinetic studies, the (A-II)rHDL acted as competitive inhibitors of HL
      mediated phospholipid hydrolysis in (A-I)rHDL. Less expected was the observation
      that the rate of phospholipid hydrolysis in (A-II)rHDL was enhanced when (A
      I)rHDL were also present in the incubation mixture. The rate of phospholipid
      hydrolysis in (A-I/A-II)rHDL was also greater than in (A-II)rHDL, indicating that
      apoA-I enhances phospholipid hydrolysis when it is present as a component of (A
      I/A-II)rHDL. It is concluded that apoA-I enhances HL-mediated phospholipid
      hydrolysis in apoA-II containing rHDL, irrespective of whether the apoA-I is
      present in the same particle as the apoA-II [as in (A-I/A-II)rHDL] or whether it
      is present as a component of a different particle, such as when (A-I)rHDL are
      added to incubations of (A-II)rHDL.

PMID- 11331015
TI  - Cysteine mutagenesis of the amino acid residues of transmembrane helix I in the
      melibiose carrier of Escherichia coli.
AB  - The melibiose carrier of Escherichia coli is a sugar-cation cotransport system
      that utilizes Na(+), Li(+), or H(+). This membrane transport protein consists of
      12 transmembrane helices. Starting with the cysteine-less melibiose carrier,
      cysteine has been substituted individually for amino acids 17-37, which includes
      all of the residues in membrane helix I. The carriers with cysteine substitutions
      were studied for their transport activity and the effect of the water soluble
      sulfhydryl reagent p-chloro- mercuribenzenesulfonic acid (PCMBS). Cysteine
      substitution caused loss of transport activity in six of the mutants (G17C, K18C,
      D19C, Y32C, T34C, and D35C). PCMBS caused greater than 50% inhibition in eleven
      mutants (F20C, A21C, I22C, G23C, I24C, V25C, Y26C, M27C, Y28C, M30C, and Y31C).
      We suggest that the residues whose cysteine derivatives were inhibited by PCMBS
      face the aqueous channel and that helix I is completely surrounded by aqueous
      environment. Second site revertants were isolated from K18C and Y31C. The
      revertants were found to have mutations in helices I, IV, and VII.

PMID- 11331016
TI  - Arginine 454 and lysine 370 are essential for the anion specificity of the
      organic anion transporter, rOAT3.
AB  - Organic anion transporters (OATs) and organic cation transporters (OCTs) mediate
      the flux of xenobiotics across the plasma membranes of epithelia. Substrates of
      OATs generally carry negative charge(s) whereas substrates of OCTs are cations.
      The goal of this study was to determine the domains and amino acid residues
      essential for recognition and transport of organic anions by the rat organic
      anion transporter, rOAT3. An rOAT3/rOCT1 chimera containing transmembrane domains
      1-5 of rOAT3 and 6-12 of rOCT1 retained the specificity of rOCT1, suggesting that
      residues involved in substrate recognition reside within the carboxyl-terminal
      half of these transporters. Mutagenesis of a conserved basic amino acid residue,
      arginine 454 to aspartic acid (R454D), revealed that this amino acid is required
      for organic anion transport. The uptakes of p-aminohippurate (PAH), estrone
      sulfate, and ochratoxin A were approximately 10-, approximately 48-, and
      approximately 32-fold enhanced in oocytes expressing rOAT3 and were only
      approximately 2-, approximately 6-, and approximately 5-fold enhanced for R454D.
      Similarly, mutagenesis of the conserved lysine 370 to alanine (K370A) suggested
      that K370 is important for organic anion transport. Interestingly, the charge
      specificity of the double mutant, R454DK370A, was reversed in comparison to rOAT3
      R454DK370A preferentially transported the organic cation, MPP(+), in comparison
      to PAH (MPP(+) uptake/PAH uptake = 3.21 for the double mutant vs 0.037 for
      rOAT3). These data indicate that arginine 454 and lysine 370 are essential for
      the anion specificity of rOAT3. The studies provide the first insights into the
      molecular determinants that are critical for recognition and translocation of
      organic anions by a member of the organic anion transporter family.

PMID- 11331017
TI  - Mutational effects on conformational changes of the dephospho- and phospho-forms
      of the Na+,K+-ATPase.
AB  - Gly263 of the rat kidney Na(+),K(+)-ATPase is highly conserved within the family
      of P-type ATPases. Mutants in which Gly263 or the juxtaposed Arg264 had been
      replaced by alanine were expressed at high levels in COS-1 cells and
      characterized functionally. Titrations of Na(+),K(+), ATP, and vanadate
      dependencies of Na(+),K(+)-ATPase activity showed changes in the apparent
      affinities relative to wild-type compatible with a displacement of the E(1)-E(2)
      conformational equilibrium in favor of E(1). The level of the K(+)-occluded form
      was reduced in the Gly263-->Ala and Arg264-->Ala mutants, and the rate constant
      characterizing deocclusion of K(+) or Rb(+) was increased as much as 20-fold in
      the Gly263-->Ala mutant. Studies of the sensitivity of the phosphoenzyme to K(+)
      and ADP showed a displacement of the E(1)P-E(2)P equilibrium of the phosphoenzyme
      in favor of E(1)P, and dephosphorylation experiments carried out at 25 degrees C
      on a millisecond time scale using a quenched-flow technique demonstrated a
      reduction of the E(1)P to E(2)P conversion rate in the mutants. Hence, the
      mutations displaced the conformational equilibria of dephosphoenzyme and
      phosphoenzyme in parallel in favor of the E(1) and E(1)P forms. The observed
      effects were more pronounced in the Gly263-->Ala mutant compared with the Arg264-
      >Ala mutant. Leu332 mutations that likewise displaced the conformational
      equilibria in favor of E(1) and E(1)P were also studied. Unlike the Gly263-->Ala
      mutant the Leu332 mutants displayed a wild-type like rate of K(+) deocclusion.
      Thus, the effect of the Gly263 mutation on the E(1)-E(2) conformational
      equilibrium seems to be caused mainly by an acceleration of the K(+)-deoccluding
      step, whereas in the Leu332 mutants the rate of the reverse reaction seems to be
      reduced.

PMID- 11331018
TI  - Determination of the midpoint potential of the FAD and FMN flavin cofactors and
      of the 3Fe-4S cluster of glutamate synthase.
AB  - Glutamate synthase is a complex iron-sulfur flavoprotein that catalyzes the
      reductive transfer of the L-glutamine amide group to C(2) of 2-oxoglutarate,
      forming two molecules of L-glutamate. The bacterial enzyme is an alphabeta
      protomer, which contains one FAD (on the beta subunit, approximately 50 kDa), one
      FMN (on the alpha subunit, approximately 150 kDa), and three different Fe-S
      clusters (one 3Fe-4S center on the alpha subunit and two 4Fe-4S clusters at an
      unknown location). To address the problem of the intramolecular electron pathway,
      we have measured the midpoint potential values of the flavin cofactors and of the
      3Fe-4S cluster of glutamate synthase in the isolated alpha and beta subunits and
      in the alphabeta holoenzyme. No detectable amounts of flavin semiquinones were
      observed during reductive titrations of the enzyme, indicating that the midpoint
      potential value of each flavin(ox)/flavin(sq) couple is, in all cases,
      significantly more negative than that of the corresponding flavin(sq)/flavin(hq)
      couple. Association of the two subunits to form the alphabeta protomer does not
      alter significantly the midpoint potential value of the FMN cofactor and of the
      3Fe-4S cluster (approximately -240 and -270 mV, respectively), but it makes that
      of FAD some 40 mV less negative (approximately -340 mV for the beta subunit and 
      300 mV for FAD bound to the holoenzyme). Binding of the nonreducible NADP(+)
      analogue, 3-aminopyridine adenine dinucleotide phosphate, made the measured
      midpoint potential value of the FAD cofactor approximately 30-40 mV less negative
      in the isolated beta subunit, but had no effect on the redox properties of the
      alphabeta holoenzyme. This result correlates with the formation of a stable
      charge-transfer complex between the reduced flavin and the oxidized pyridine
      nucleotide in the isolated beta subunit, but not in the alphabeta holoenzyme.
      Binding of L-methionine sulfone, a glutamine analogue, had no significant effect
      on the redox properties of the enzyme cofactors. On the contrary, 2-oxoglutarate
      made the measured midpoint potential value of the 3Fe-4S cluster approximately 20
      mV more negative in the isolated alpha subunit, but up to 100 mV less negative in
      the alphabeta holoenzyme as compared to the values of the corresponding free
      enzyme forms. These findings are consistent with electron transfer from the entry
      site (FAD) to the exit site (FMN) through the 3Fe-4S center of the enzyme and the
      involvement of at least one of the two low-potential 4Fe-4S centers, which are
      present in the glutamate synthase holoenzyme, but not in the isolated subunits.
      Furthermore, the data demonstrate a specific role of 2-oxoglutarate in promoting
      electron transfer from FAD to the 3Fe-4S cluster of the glutamate synthase
      holoenzyme. The modulatory role of 2-oxoglutarate is indeed consistent with the
      recently determined three-dimensional structure of the glutamate synthase alpha
      subunit, in which several polypeptide stretches are suitably positioned to
      mediate communication between substrate binding sites and the enzyme redox
      centers (FMN and the 3Fe-4S cluster) to tightly control and coordinate the
      individual reaction steps [Binda, C., et al. (2000) Structure 8, 1299-1308].

PMID- 11331019
TI  - Hypersensitization of tumor cells to glycolytic inhibitors.
AB  - The slow growth of cells in the inner core of solid tumors presents a form of
      multidrug resistance to most of the standard chemotherapeutic agents, which
      target the outer more rapidly dividing cells. However, the anaerobic environment
      of the more centrally located tumor cells also provides an opportunity to exploit
      their dependence on glycolysis for therapeutic gain. We have developed two in
      vitro models to investigate this possibility. Model A represents osteosarcoma
      wild-type (wt) cells treated with agents which inhibit mitochondrial oxidative
      phosphorylation (Oxphos) by interacting with complexes I, III, and V of the
      electron transport chain in different ways, i.e., rhodamine 123 (Rho 123),
      rotenone, antimycin A, and oligomycin. All of these agents were found to
      hypersensitize wt cells to the glycolytic inhibitor 2-deoxyglucose. Cells treated
      with Rho 123 also become hypersensitive to oxamate, an analogue of pyruvate,
      which blocks the step of glycolysis that converts pyruvate to lactic acid. Model
      B is rho(0) cells which have lost their mitochondrial DNA and therefore cannot
      undergo Oxphos. These cells are 10 and 4.9 times more sensitive to 2-deoxyglucose
      and oxamate, respectively, than wt cells. Lactic acid levels, which are a measure
      of anaerobic metabolism, were found to be > 3 times higher in rho(0) than in wt
      cells. Moreover, when wt cells were treated with Rho 123, lactic acid amounts
      increased as a function of increasing Rho 123 doses. Under similar Rho 123
      treatment, rho(0) cells did not increase their lactic acid levels. These data
      confirm that cell models A and B are similarly sensitive to glycolytic inhibitors
      due to their dependence on anaerobic metabolism. Overall, our in vitro results
      suggest that glycolytic inhibitors could be used to specifically target the slow
      growing cells of a tumor and thereby increase the efficacy of current
      chemotherapeutic and irradiation protocols designed to kill rapidly dividing
      cells. Moreover, glycolytic inhibitors could be particularly useful in
      combination with anti-angiogenic agents, which, a priori, should make tumors more
      anaerobic.

PMID- 11331020
TI  - Substrate specificity of the heparan sulfate hexuronic acid 2-O-sulfotransferase.
AB  - The interaction of heparan sulfate with different ligand proteins depends on the
      precise location of O-sulfate groups in the polysaccharide chain. We have
      previously shown that overexpression in human kidney 293 cells of a mouse
      mastocytoma 2-O-sulfotransferase (2-OST), previously thought to catalyze the
      transfer of sulfate from 3'-phosphoadenosine 5'-phosphosulfate to C2 of L
      iduronyl residues, preferentially increases the level of 2-O-sulfation of D
      glucuronyl units [Rong, J., Habuchi, H., Kimata, K., Lindahl, U., and Kusche
      Gullberg, M. (2000) Biochem. J. 346, 463-468]. In the study presented here, we
      further investigated the substrate specificity of the mouse mastocytoma 2-OST.
      Different polysaccharide acceptor substrates were incubated with cell extracts
      from 2-OST-transfected 293 cells together with the sulfate donor 3'
      phosphoadenosine 5'-phospho[(35)S]sulfate. Incubations with O-desulfated heparin,
      predominantly composed of [(4)alphaIdoA(1)-(4)alphaGlcNSO(3)(1)-](n)(), resulted
      in 2-O-sulfation of iduronic acid. When, on the other hand, an N-sulfated
      capsular polysaccharide from Escherichia coli K5, with the structure
      [(4)betaGlcA(1)-(4)alphaGlcNSO(3)(1)-](n)(), was used as an acceptor, sulfate was
      transferred almost exclusively to C2 of glucuronic acid. Substrates containing
      both iduronic and glucuronic acid residues in about equal proportions strongly
      favored sulfation of iduronic acid. In agreement with these results, the 2-OST
      was found to have a approximately 5-fold higher affinity for iduronic acid
      containing substrate disaccharide units (K(m) approximately 3.7 microM) than for
      glucuronic acid-containing substrate disaccharide units (K(m) approximately 19.3
      microM).

PMID- 11331021
TI  - How different DNA-binding proteins affect long-range oxidative damage to DNA.
AB  - Here the effect on DNA-mediated charge transport of binding by a variety of
      proteins is examined. DNA assemblies were constructed that contain a tethered
      rhodium intercalator, as photooxidant, as well as two 5'-GG-3' sites flanking the
      DNA-binding site for the different proteins. By monitoring the ratio of oxidative
      damage promoted at the guanine doublet situated distal to the protein-binding
      site versus that at the proximal site as a function of protein binding, the
      effects of binding the proteins on DNA-mediated charge transport were determined.
      Proteins examined included both the wild-type and mutant methyltransferase,
      M.HhaI, which are base-flipping enzymes, the restriction endonuclease R.PvuII, a
      TATA-binding protein, which kinks the DNA, and the transcription factor
      Antennapedia homeodomain protein, which binds DNA through a helix-turn-helix
      motif. In general, it was observed that yields of long-range oxidative damage
      correlate with protein-dependent alterations in DNA base stacking. Interactions
      that disturb the DNA pi-stack inhibit DNA charge transport. Alternatively,
      interactions that promote no helix distortion but, as a result of tight packing,
      may rigidify the pi-stack, serve instead to enhance the ability of the DNA base
      pairs to serve as a conduit for charge transport. Thus, protein binding to DNA
      modulates long-range charge transport both negatively and positively, depending
      upon the specific protein/DNA interactions in play. Long-range DNA charge
      transport and this modulation by protein binding may be important to consider
      physiologically.

PMID- 11331022
TI  - Role of the major homology region in assembly of HIV-1 Gag.
AB  - The major homology region (MHR) is a highly conserved sequence in the gag gene of
      all retroviruses, including HIV-1. Its role in assembly is unknown, but deletion
      of the motif significantly impairs membrane binding and viral particle formation.
      To begin characterizing this defect, we have determined the contribution of this
      region to the energetics of the assembly process. Intrinsic fluorescence studies
      were conducted to determine the change in free energy associated with membrane
      and RNA binding using tRNA and large unilamellar vesicles of 1-palmitoyl-2
      oleoylphosphatidylserine as models. For the wild-type protein, the change in free
      energy was within RT [600 cal/(mol.K)] whether Gag binds first to RNA or to the
      membrane. Thus, the initial binding of Gag can be to either substrate, but in
      vivo conditions favor initial association to RNA presumably due to its higher
      local concentration. After establishing the pattern of assembly, we compared the
      binding energy of Gag(WT) versus the deletion mutant, Gag(Delta)(MHR). Gag(WT)
      bound to membranes with a 2-fold higher affinity than Gag(Delta)(MHR), and the
      binding to RNA was similar for the two proteins. Gag prebound to RNA or to
      membrane exhibited approximately 2-4-fold greater binding affinity than
      Gag(Delta)(MHR) for binding the membrane or RNA, respectively. Most importantly,
      the mutant was significantly impaired in its ability to self-associate on RNA or
      on membrane surfaces. This key role of the MHR in promoting productive protein
      protein interactions was also seen in altered amounts of cleavage products and
      the lack of membrane-bound, RNA-containing replication intermediates in infected
      cells. These results suggest that Gag first binds to RNA and then assembles into
      a multimeric complex with a large membrane-binding face that facilitates
      subsequent membrane binding. Deletion of the MHR disrupts the protein-protein
      interactions required to complete this process.

PMID- 11331023
TI  - A bacteriochlorophyll a antenna complex from purple bacteria absorbing at 963 nm.
AB  - A recently isolated species of the photosynthetic purple sulfur bacteria,
      provisionally called strain 970, was investigated with respect to its antenna
      function by means of various spectroscopic techniques, including fluorescence and
      pump-probe absorption difference spectroscopy. The bacterium contains
      bacteriochlorophyll a and an as yet unidentified carotenoid, perhaps 3,4,3',4'
      tetrahydrospirilloxanthin. It has a single antenna complex of the LH1 type, with
      a Q(y) absorption band situated at the unusually long wavelength of 963 nm at
      room temperature and 990 nm at 6 K. In contrast to many other species, the
      reaction center showed two well-separated absorption bands of bacteriopheophytin
      at 6 K, located at 747 and 762 nm. The primary electron donor showed a bleaching
      band centered at 925 nm upon photooxidation. Thus, the energy gap between LH1 and
      the primary electron donor is quite large in this strain: 425 cm(-1).
      Nevertheless, trapping occurred with a time constant of 65 +/- 5 ps, similar to
      the rates observed in other purple bacteria. As in other species, no back
      transfer from the reaction center to the antenna was observed. Our results show
      that strain 970 is a unique subject for the study of antenna and reaction center
      function and organization.

PMID- 11331024
TI  - A web of dependence.

PMID- 11331025
TI  - Addiction research in Germany makes progress--however, it has a long way to go to
      contribute significantly to the international community of research and care.

PMID- 11331026
TI  - Part of the invisible college.

PMID- 11331027
TI  - A meta-analysis comparing buprenorphine to methadone for treatment of opiate
      dependence.
AB  - BACKGROUND: The unique pharmacological properties of buprenorphine may make it a
      useful maintenance therapy for opiate addiction. This meta-analysis considers the
      effectiveness of buprenorphine relative to methadone. METHODS: A systematic
      literature search identified five randomized clinical trials comparing
      buprenorphine to methadone. Data from these trials were obtained. Retention in
      treatment was analyzed with a Cox proportional hazards regression. Urinalyses for
      opiates were studied with analysis of variance and a common method of handling
      missing values. A meta-analysis was used to combine these results. RESULTS:
      Subjects who received 8-12 mg/day buprenorphine had 1.26 times the relative risk
      of discontinuing treatment (95% confidence interval 1.01-1.57) and 8.3% more
      positive urinalyses (95% confidence interval 2.7-14%) than subjects receiving 50
      80 mg/day methadone. Buprenophrine was more effective than 20-35 mg/day
      methadone. There was substantial variation in outcomes in the different trials.
      CONCLUSIONS: The variation between trials may be due to differences in dose
      levels, patient exclusion criteria and provision of psychosocial treatment. The
      difference in the effectiveness of buprenorphine and methadone may be
      statistically significant, but the differences are small compared to the wide
      variance in outcomes achieved in different methadone treatment programs. Further
      research is needed to determine if buprenorphine treatment is more effective than
      methadone in particular settings or in particular subgroups of patients.

PMID- 11331028
TI  - A view through the gateway: expectancies as a possible pathway from alcohol to
      cannabis.
AB  - AIM: The aim of this study was to test the hypothesis that cannabis outcome
      expectancies would be more positive in adolescents who drink alcohol than in non
      drinkers. PARTICIPANTS AND SETTING: The participants in the study were 4544 11-16
      year-olds attending eight secondary schools located in the north-west midlands of
      England. PROCEDURE: Participants completed an anonymous self-report questionnaire
      that incorporated sections designed to tap adolescents' expectancies of positive
      and negative outcomes of alcohol and cannabis use, together with other questions
      relating to substance use and associated issues. RESULTS: Four reliable six-item
      scales were derived, and used to measure positive and negative alcohol and
      cannabis outcome expectancies. Negative expectancies were relatively stable
      across age and frequency of substance use, particularly for alcohol. However,
      positive expectancies for both substances increased markedly with age and,
      independently, with frequency of use. Positive alcohol and cannabis outcome
      expectancies were meaningfully related to expectancies of future substance use,
      and to measures of problem drug use and resistance to peer influence, supporting
      the validity of these expectancy measures, and their possible value as diagnostic
      screening instruments. The main hypothesis of the study was supported: among
      respondents who reported never using cannabis, positive cannabis outcome
      expectancies increased and negative cannabis outcome expectancies decreased with
      increasing frequency of alcohol use. CONCLUSIONS: The results are consistent with
      a version of the 'gateway hypothesis' for the relationship between alcohol and
      cannabis use (alcohol use leads to changes in cannabis expectancies and thereby
      to cannabis use), but a proper test of the hypothesis requires a longitudinal
      study.

PMID- 11331029
TI  - Factors affecting the initiation of substance abuse treatment in managed care.
AB  - AIMS: A long-standing concern of clinicians in addiction treatment is that a
      large number of individuals who are admitted to treatment do not return to
      actually begin the program. We identified characteristics that predict treatment
      initiation. DESIGN: In-person structured interviews were conducted with
      consecutive admissions to a large outpatient program (N = 1204), and the health
      plan's automated registration data were used to determine treatment attendance.
      We compared those who returned to begin treatment with those who did not.
      SETTING: The study was conducted at the Chemical Dependency program of a large
      group model health maintenance organization (HMO). PARTICIPANTS: Study subjects
      were individuals age 18 or over admitted to the program. MEASUREMENT: Study
      variables included DSM-IV alcohol and drug dependence and abuse, Addiction
      Severity Index problem severity, motivation and treatment entry measures.
      FINDINGS: Those who were drug-dependent were less likely to begin treatment than
      those dependent only on alcohol. Measures of motivation, such as work-place
      pressures and the patient's perception of the importance of alcohol treatment,
      predicted starting treatment for individuals who were alcohol-dependent only or
      alcohol- and drug-dependent. Among patients who were dependent only on alcohol,
      women were more likely than men to start treatment, and for those who were drug
      dependent, being employed and having higher drug severity scores predicted
      starting treatment. CONCLUSIONS: Screening at intake may identify those at risk
      of not returning after admission to start treatment. Clinicians may consider
      making additional efforts during the intake process to engage individuals who are
      unemployed and have drug (as opposed to alcohol) disorders and less motivation.

PMID- 11331030
TI  - Syringe borrowing persists in Dublin despite harm reduction interventions.
AB  - AIMS: To measure the frequency of syringe borrowing in young Irish injecting drug
      users (IDUs) and identify associated characteristics. DESIGN: Cross-sectional
      survey. SETTING: Addiction treatment services in Dublin. PARTICIPANTS: Treated
      IDUs (N = 246). MEASUREMENTS: Data on drug injecting and syringe borrowing in the
      previous 6 months. FINDINGS: The median age was 22 years and the median length of
      injecting history was 19 months. Syringe borrowing was reported by 173 (70.3%)
      participants. A multivariate analysis identified seven characteristics
      significantly associated with syringe borrowing. These included early school
      leaving and parental unemployment. IDUs with long injecting histories who had
      injected less frequently were more likely to borrow. Injection of more than one
      substance was significantly associated with borrowing of syringes. Syringe
      borrowing was associated with having more intimate social relationships with
      other IDUs, less perceived risk in borrowing from acquaintances and usually
      opting to inject in the company of other IDUs. CONCLUSIONS: Syringe borrowing is
      commonly practised by young IDUs. Those with a background of social deprivation
      are more likely to engage in this risk behaviour. IDUs who report borrowing are
      more intimately involved with other IDUs and tend to perceive less risk or
      dangerousness in borrowing. In addition to syringe exchange, there is a need to
      work cognitively with IDUs to identify and challenge assumptions that they may
      have regarding the safety involved in borrowing from others, particularly from
      those with whom they have close social relationships.

PMID- 11331031
TI  - Causes of death of patients with substance dependence: a record-linkage study in
      a psychiatric hospital in Taiwan.
AB  - AIMS: The causes of death among a series of patients with substance dependence
      were investigated. SETTING: A psychiatric teaching hospital in Taipei, Taiwan
      (Taipei City Psychiatric Center). PARTICIPANTS: A total of 1698 patients with
      various diagnostic categories of substance dependence, who had been admitted to
      TCPC for detoxification were followed-up from 1985 to 1996. DESIGN: A record
      linkage study was performed using the patient's national identification number to
      link between TCPC chart records and the mortality file compiled by the National
      Department of Health. Risk factor analyses for mortality included socio
      demographic data, clinical diagnosis and cause of death. FINDINGS: A total of 141
      patients died during the study period. Among them, 83 had a diagnosis of alcohol
      dependence, 41 of heroin dependence and the remaining 17 cases of sedative, glue
      or hallucinogen dependence. The annual mortality rate of patients with heroin
      dependence was 1.94%. Accidental death is the leading cause of death among
      patients with heroin dependence. However, the patients with alcohol dependence
      had a higher mortality risk than those with heroin dependence (relative hazard =
      1.91, p < 0.001) in this study. The proportion of non-violent death was
      significantly higher among the patients with alcohol dependence than those with
      heroin dependence (p < 0.005). CONCLUSION: The causes of death among patients
      with substance dependence found in this Taiwanese series were very similar to
      those reported in the western literature. However, differences included the
      absence of death among heroin addicts due to HIV-related disease and a markedly
      high percentage of alcoholic patients who died of liver diseases.

PMID- 11331032
TI  - Cannabis use and dependence among Australian adults: results from the National
      Survey of Mental Health and Wellbeing.
AB  - AIMS: To examine: (i) the prevalence of cannabis use and DSM-IV cannabis
      dependence among Australian adults, and (ii) correlates of level of cannabis
      involvement. DESIGN: Cross-sectional survey assessing substance use and DSM-IV
      substance use disorders (abuse and dependence). Setting and participants. A
      household survey of a nationally representative sample of 10 641 Australians aged
      18 years and older. MEASUREMENTS: Trained interviewers administered a structured,
      modified version of the Composite International Diagnostic Interview (CIDI).
      FINDINGS: In the past 12 months, 2.2% (95%CI:1.8, 2.6) of adults were diagnosed
      with DSM-IV cannabis use disorder, comprising cannabis dependence (1.5%; 95%CI:
      1.2, 1.8) and cannabis abuse (0.7%, 95%CI: 0.6, 0.8). Almost one-third of
      cannabis users (31.7%; 95%CI: 27.7, 35.7) met criteria for cannabis dependence
      (21%; 95%CI: 16.7, 25.3) and abuse (10.7%; 95%CI: 8.0, 13.4). Multinomial
      logistic regression revealed that compared to non-dependent cannabis users, non
      users were more likely to be female, aged 25 + years, out of the labour force and
      married/de facto, and displayed lower levels of co-morbidity. In contrast,
      dependent cannabis users were more likely to be 18-24 years old, unemployed, and
      displayed higher levels of co-morbidity than non-dependent users. CONCLUSIONS:
      Cannabis use disorders affect approximately 300 000 Australian adults. A better
      understanding of the factors associated with cannabis dependence may help
      identify groups who have difficulties controlling use and aid the development of
      strategies for reducing cannabis-related harm.

PMID- 11331033
TI  - In and out of the K-hole: a comparison of the acute and residual effects of
      ketamine in frequent and infrequent ketamine users.
AB  - AIMS: Ketamine, a non-competitive NMDA receptor antagonist, produces acute
      impairments of working, episodic and semantic memory along with psychotogenic and
      dissociative effects when a single dose is given to healthy volunteers. In
      recreational users, Curran & Morgan (2000) showed that ketamine produced the same
      acute effects but that 3 days after ingestion, ketamine users showed persisting
      memory impairment and elevated psychotogenic symptoms compared with controls. To
      explore whether such persisting effects reflect chronic effects of ketamine use,
      the present study compared frequent with infrequent users of ketamine on the
      night of drug use and again 3 days later. DESIGN AND PARTICIPANTS: Eighteen
      frequent and 19 infrequent ketamine users were assessed on each test day on a
      range of cognitive tasks tapping memory and attentional function and on
      subjective scales (schizotypal symptomatology, dissociation, mood). FINDINGS:
      Groups were broadly matched for polydrug use apart from ketamine which frequent
      users took significantly more often and in larger quantities than infrequent
      users. Acute effects on day 0 replicated previous findings. On day 3 frequent
      users showed significant impairments on tasks tapping episodic and semantic
      memory but there was no evidence of persisting dissociative or schizotypal
      symptoms. CONCLUSION: These findings indicate that frequent use of ketamine
      produces long-lasting impairments in episodic memory and aspects of retrieval
      from semantic memory. Such effects accord with animal evidence of the effects of
      NMDA receptor blockade on memory. Those using, or contemplating using ketamine
      should be informed of these persisting, detrimental effects of the drug upon
      human memory.

PMID- 11331034
TI  - Ways of coping and the health of relatives facing drug and alcohol problems in
      Mexico and England.
AB  - AIMS: To compare two contrasting socio-cultural groups in terms of parameters
      relating to the stress - coping - health model of alcohol, drugs and the family,
      and to test hypotheses derived from the model in each of the two groups
      separately. DESIGN: Cross-sectional, comparative and correlational, using
      standard questionnaire data, supplemented by qualitative interview data to
      illuminate the findings. PARTICIPANTS: One hundred close relatives, mainly
      partners or parents, from separate families in Mexico City, and 100 from South
      West England. Data sources. Coping Questionnaire (CQ), Family Environment Scale
      (FES), Symptom Rating Test (SRT), Semi-structured interview. FINDINGS: Mean
      symptom scores were high in both groups, and not significantly different. The
      hypothesis that relatives in Mexico City, a more collectivist culture, would show
      more tolerant - inactive coping was not supported, but there was support for the
      prediction that relatives in South West England would show more withdrawal
      coping. This result may be as much due to differences in poverty and social
      conditions as to differences in individualism - collectivism. As predicted by the
      stress - coping - health model, tolerant - inactive coping was correlated with
      symptoms, in both groups, after controlling for family conflict, but there was
      only limited support for a moderating role of coping. Wives of men with alcohol
      problems in Mexico City, and wives of men with other drug problems in South West
      England, reported particularly high levels of both engaged and tolerant -
      inactive coping. CONCLUSIONS: Tolerant - inactive coping may be bad for
      relatives' health: causality may be inferred but is not yet proved. Certain
      groups are more at risk of coping in this way. Qualitative data help understand
      the nature of tolerant - inactive coping and why it occurs despite the view of
      relatives themselves that it is counter-productive.

PMID- 11331035
TI  - IFN-beta1b augments glucocorticoid-induced suppression of tumor necrosis factor
      alpha production by increasing the number of glucocorticoid receptors on a human
      monocytic cell line.
AB  - We studied the effect of recombinant interferon-beta1b (IFN-beta1b) on the
      sensitivity to glucocorticoids (GC) and on the number of GC receptors (GCR) in
      the human monocytic cell line THP-1. We found that IFN-beta1b augments the
      suppressive effect that dexamethasone has on the stimulated production of tumor
      necrosis factor-alpha (TNF-alpha), most likely related to the increased number of
      GCR observed after exposure to IFN-beta1b. This provides a possible clue to the
      mechanism of action of IFN-beta in multiple sclerosis.

PMID- 11331036
TI  - Regulation by IFN-beta of inducible nitric oxide synthase and interleukin-12/p40
      in murine macrophages cultured in the presence of Chlamydia pneumoniae antigens.
AB  - Chlamydia pneumoniae has been demonstrated in the cerebrospinal fluid (CSF) of
      patients with multiple sclerosis (MS). Interferon-beta (IFN-beta) has favorable
      effects on the clinical course of MS. We investigated whether the beneficial
      effects of IFN-beta in MS may involve its role in regulating nitric oxide (NO)
      and interleukin-12 (IL-12) in macrophages, as these immune modulators form part
      of the innate immune response to intracellular pathogens, such as C. pneumoniae.
      Murine macrophages in cultures exposed to elementary body antigens or recombinant
      major outer membrane protein (rMOMP) of C. pneumoniae demonstrate a significant
      increase in NO as well as production of IL-12/p40 in culture supernatants
      compared with basal levels. Addition of murine IFN-beta increased NO activity in
      murine macrophages cultured with chlamydial antigens. Addition of neutralizing
      anti-IFN-beta antibody prevented the NO increase. In contrast to its effect on
      inducible NO synthase (iNOS), IFN-beta reduced induction of IL-12/p40 following
      culture with either elementary body antigens or rMOMP. Inhibition was reversed
      with anti-IFN-beta antibody. If C. pneumoniae infection is responsible for the
      inflammatory response in the pathogenesis of MS, the beneficial effects of IFN
      beta in MS may be due to its enhancing intracellular NO activity while inhibiting
      secretion of the proinflammatory cytokine, IL-12.

PMID- 11331037
TI  - Dexamethasone promotes type 2 cytokine production primarily through inhibition of
      type 1 cytokines.
AB  - Glucocorticoids, at concentrations mimicking stress-physiologic plasma levels,
      cause an in vitro shift in the type 1/type 2 cytokine balance of human peripheral
      blood mononuclear cells (PBMC) toward a predominant type 2 response. The
      mechanisms of these immune alterations are currently unknown but may involve
      modulation of key cytokines known to regulate the type 1/type 2 cytokine balance.
      Therefore, we sought to determine the role of cytokines previously reported to
      regulate the type 1/type 2 cytokine balance, including interleukin-12 (IL-12),
      interferon-gamma (IFN-gamma, IL-10, IL-4, and IL-13, in the glucocorticoid
      mediated human type 1/type 2 cytokine alterations. Human PBMC were stimulated in
      vitro with tetanus toxoid in the presence of 10(-8) M dexamethasone (DEX).
      Cultures were supplemented with recombinant human (rHuIL-12), rHuIFN-gamma, or
      neutralizing monoclonal antibodies (mAb) against IL-4, IL-10, or IL-13. DEX
      decreased IFN-gamma production and increased IL-4 and IL-10 production by tetanus
      stimulated PBMC. The addition of either recombinant IL-12p70 or IFN-gamma
      abrogated the DEX-mediated decrease in IFN-gamma and increase in IL-4 production.
      Neutralization of IL-4 activity partially abrogated the DEX-induced alterations
      in IFN-gamma and IL-4, but not IL-10, production. Neutralization of IL-10 or IL
      13 had no effect on the Dex-mediated type 1/type 2 cytokine alterations.
      Therefore, the DEX-mediated type 1/type 2 cytokine alterations in tetanus
      stimulated PBMC are primarily the result of downregulation of type 1 cytokines,
      subsequently permitting the production of type 2 cytokines.

PMID- 11331038
TI  - Acute activation of gp130 gene expression in bone marrow stromal cells by contact
      with myeloma-derived lymphoblastic cell line ARH77 cell membranes.
AB  - Cell-cell contact of myeloma-derived cell lines (MDCL) or fresh myeloma cells
      with bone marrow stromal cells (BMSC) is known to induce interleukin-6 (IL-6) and
      matrix metalloproteinase-1 (MMP-1) production by a marrow stromal cell line. To
      determine if other BMSC transcripts are altered during cell-cell contact between
      BMSC and tumor cells, we have used cell lines ARH77 and U266 in an in vitro
      model. Using mRNA differential display and reverse transcriptase-polymerase chain
      reaction (RT-PCR), it was determined that a total of 141 transcripts were either
      upregulated or downregulated in the BMSC on contact with cell membrane from cell
      lines ARH77 and U266. Induction of two of these transcripts, interleukin-6 (IL-6)
      and gp130 in the BMSC by ARH77 cell membranes was studied in greater detail. Real
      time PCR was used to quantitate transcript levels of gp130, IL-6, and 36b4, a
      housekeeping gene. Cycloheximide (CHX) alone increased both gp130 and IL-6
      transcripts in the BMSC. In addition, CHX caused a superinduction of these
      transcripts in BMSC exposed to ARH77 cell membranes. The induction of gp130 was
      independent of the increase in IL-6 mRNA. Upregulation of gp130, a component of
      the membrane receptors for the IL-6 superfamily, can have profound effects on the
      response of BMSC to the IL-6 superfamily of cytokines.

PMID- 11331039
TI  - Immunoglobulin subclasses in patients with neutralizing and nonneutralizing
      antibodies against IFN-beta1b.
AB  - Treatment of multiple sclerosis (MS) with interferon-beta1b (IFN-beta1b) induces
      the production of antibodies in some patients. A proportion of these antibodies
      can reduce the biologic activity of IFN-beta, and they are, therefore, referred
      to as neutralizing antibodies (NAB). The remaining antibodies do not interfere
      with the biologic activity of IFN-beta and are referred to as nonneutralizing
      antibodies (NNAB) in this paper. Immunoglobulin (Ig) subtyping of these
      antibodies was carried out, and Ig subclass patterns in 20 patients with NAB were
      compared with those of NNAB in 39 patients. In patients with NAB, IgG2 and IgG4
      were found to occur more frequently than in patients with NNAB (30% vs. 3%, p =
      0.05, and 55% vs. 18%, p = 0.003, respectively) The NAB titer correlated strongly
      with the IgG4 titer (r = 0.53, p = 0.02). Median total IgG, IgG1, and IgG4 titers
      were significantly higher in NAB than in NNAB patients (respectively, 8000 vs.
      3200, p = 0.01; 1600 vs. 400, p = 0.0004; 200 vs. 0, p = 0.004). It is concluded
      that the development of NAB is related to both the quantity and the quality of
      the antibodies against IFN-beta1b.

PMID- 11331040
TI  - Expression of the interleukin-18 gene from rhesus macaque by the simian
      immunodeficiency virus does not result in increased viral replication.
AB  - Interleukin-18 (IL-18), previously known as interferon-gamma (IFN-gamma)-inducing
      factor (IGIF), is a proinflammatory cytokine expressed by activated macrophages
      that acts in synergy with IL-12 as an important amplifying factor for IFN-gamma
      production and Th1 development. To study the effect of IL-18 on a lentiviral
      infection, we cloned the IL-18 gene from a rhesus macaque and constructed
      replication-competent simian immunodeficiency virus (SIV) that expressed either
      the precursor pro-IL-18 (SIV(IL-18)) or the mature form (SIV(mIL-18)) of IL-18.
      The predicted amino acid sequence for rhesus IL-18 had 96% homology with the
      human one, differing in only 8 of 193 residues. SIV(IL-18) and SIV(mIL-18)
      replicated more slowly than control viruses in the CEM x 174 cell line and
      resulted in the development of chronically infected cell lines that expressed
      high levels of infectious SIV. The cell line generated by SIV(IL-18) released
      large quantities of IL-18 into the supernatant, whereas the one obtained from
      SIV(mIL-18) showed the accumulation of IL-18 in the cytoplasm. Similarly, SIV(IL
      18) and SIV(mIL-18) replicated more slowly than the unmodified viral vector in
      rhesus peripheral blood mononuclear cells (PMBC), but only SIV(IL-18) expressed
      biologically active IL-18. These experiments show that the precursor form of IL
      18 is necessary for the efficient release of the cytokine and that IL-18 does not
      promote increased replication of SIV in rhesus PBMC.

PMID- 11331041
TI  - IFN-beta1a may increase serum levels of TIMP-1 in patients with relapsing
      remitting multiple sclerosis.
AB  - Serum levels of matrix metalloprotease-9 (MMP-9) and tissue inhibitor of MMP-1
      (TIMP-1) were measured monthly in 7 patients with relapsing-remitting multiple
      sclerosis (MS) 6 months before and 6 months during treatment with weekly
      intramuscular (i.m.) injections of interferon-beta1a (IFN-beta1a) 30 microg.
      Within-patient median MMP-9 levels were unchanged on treatment. Within-patient
      median TIMP-1 levels were higher during months 1-6 (771.5 ng/ml) and during
      months 4, 5, and 6 of treatment (793 ng/ml) compared with 6 months pretreatment
      (414 ng/ml) (respectively, p = 0.10, p = 0.047; Wilcoxon signed-rank test). These
      preliminary data suggest that IFN-beta1a therapy may increase TIMP-1 levels.

PMID- 11331042
TI  - Interleukin-1 or tumor necrosis factor-alpha augmented the cytotoxic effect of
      mycobacteria on human fibroblasts: application to evaluation of pathogenesis of
      clinical isolates of Mycobacterium tuberculosis and M. avium complex.
AB  - Mycobacteria-induced in vitro events reflecting human tuberculosis can contribute
      to the evaluation of the pathogenesis of Mycobacterium tuberculosis (MTB). In
      this study, we propose such an in vitro method based on live mycobacteria-induced
      cytotoxicity to human cell lines. When human lung-derived normal fibroblast cell
      line MRC-5 was infected with various strains of mycobacteria (M. tuberculosis
      H(37)Rv and H(37) Ra, Mycobacterium avium 427S and 2151SmO, and Mycobacterium
      bovis BCG Pasteur and Tokyo), the fibroblasts were killed by mycobacteria
      according to the degree of virulence. Other human originated macrophage (U-937,
      THP-1), myeloid (HL-60), and epithelial carcinoma (A549) cell lines exhibited a
      similar cytotoxic response to virulent mycobacteria. MRC-5 was most susceptible
      to virulent mycobacteria among various human cell lines examined. The
      cytotoxicity was enhanced by the proinflammatory cytokines, interleukin-1 (IL-1)
      and tumor necrosis factor-a (TNF-alpha), which in the absence of mycobacteria
      stimulate the growth of normal human fibroblasts. This in vitro evaluation system
      was applied to clinical isolates of drug-sensitive MTB (DS-MTB), drug-resistant
      MTB (DR-MTB) including multidrug-resistant (MDR-MTB), and M. avium complex (MAC).
      MTB strains (n = 24) exhibited strong cytotoxic activity, but MAC strains (n = 5)
      had only weak activity. Furthermore, there was no significant difference in
      cytotoxicity between DS-MTB (n = 11) and DR-MTB (n = 13). Collectively, these
      results suggest that this new in vitro system is useful for evaluating the
      pathogenesis of mycobacteria and that there was no difference in the pathogenesis
      between drug-susceptible and drug-resistant clinical isolates.

PMID- 11331043
TI  - An attributable cost model for a telecare system using advanced community alarms.
AB  - We have developed an attributable cost model for a city-based telecare scheme
      involving 11,618 community alarm users. The equipment was assumed to cost 500
      Pounds-1000 Pounds per installation, compared with 175 Pounds for the current
      system. Because of the significant additional capital cost of the proposed
      system, it would be necessary to borrow to finance it. For example, if the home
      equipment cost 500 Pounds per unit, an additional 2.2 million Pounds would be
      required. Nonetheless, it would be possible to achieve a return on the investment
      after 10 years. The principal savings would arise from reduced hospital bed costs
      and reduced residential care. The model suggests that the financial benefits of
      the proposed system would occur in the ratio of 4% to the local authority housing
      department, 43% to the National Health Service and 53% to the residential care
      provider.

PMID- 11331044
TI  - A prospective satisfaction study and cost analysis of a pilot child
      telepsychiatry service in Newfoundland.
AB  - We evaluated user satisfaction with a PC-based videoconferencing system used for
      child psychiatry assessments and performed a cost analysis. Thirty patients (aged
      5-16 years), accompanied by a parent, completed a psychiatric assessment using
      the videoconferencing system. One of five child psychiatrists was randomly
      assigned to each assessment. Satisfaction questionnaires were completed after
      each assessment by the psychiatrist, patient and parent. Parents also completed a
      cost questionnaire. The telecommunications bandwidth was 336 kbit/s. The
      psychiatrists stated that they were either 'very satisfied' or 'satisfied' with
      the telepsychiatry assessments. On a five-point Likert scale (1 = lowest, 5 =
      highest), 28 of the 30 parents (93%) rated their satisfaction level as 5; the
      other two rated it 4. All 30 parents (100%) stated that they 'liked' the
      telepsychiatry assessment and would use the system again. Twenty-nine parents
      (97%) indicated that they would prefer to use the telepsychiatry system to
      travelling to see a child psychiatrist in person. Eleven children (aged 5-12)
      participated and all (100%) said they 'liked' using the telepsychiatry system.
      Five out of nine children (56%) stated they liked the 'television doctor' better
      than the 'real' doctor; four said they had no preference. Nineteen adolescents
      (aged 13-16 years) participated and most were very satisfied or satisfied with
      the system. Seventeen of the 19 adolescents (89%) said they would prefer to see
      the psychiatrist on the videoconferencing system to travelling for an assessment,
      and the same number said that they would use telepsychiatry again. The estimated
      total travel cost for the 30 patients was $12,849, an average of $428 per
      patient. The total cost of the telepsychiatry service for the three-month pilot
      was $12,575, or $419 per patient.

PMID- 11331045
TI  - Low-bandwidth, Internet-based videoconferencing for physical rehabilitation
      consultations.
AB  - Low-bandwidth, Internet-based videoconferencing was used to provide physical
      rehabilitation consultation services for eight community hospitals.
      Videoconferencing and file transmission used a PC and modem. A separate telephone
      line was used for voice. Over 21 months, 47 physical rehabilitation consultations
      were completed for communication disorders, foot care, gait problems, orthotics,
      prosthetics, arm weakness and wheelchair prescription. Consultations were
      approximately 40 min long. Clinician questionnaires were completed by 47
      individuals. While more than 80% of the questionnaire responses supported the
      telemedicine approach, remote clinicians rated their satisfaction higher than did
      the specialists. Client questionnaires were completed by 24 individuals (a
      response rate of 51%). All clients were comfortable with and had confidence in
      the teleconsultations.

PMID- 11331046
TI  - Evaluation of a routine telepsychiatry service.
AB  - An assessment was undertaken of a routine telepsychiatry service in rural areas
      of a Canadian province as a follow-up to a pilot telepsychiatry project. Over two
      years, there were 546 consultations at the five participating general hospitals,
      although the level of use varied considerably between them. Health professionals
      expressed high satisfaction with the service. While there were equipment problems
      in 17% of all consultations in the second year, they did not seem to affect
      acceptance of the technique. A cost analysis comparing consultations provided by
      a visiting psychiatrist and telepsychiatry found a break-even point of 348
      consultations a year. However, when use of the videoconferencing network for
      administrative meetings was considered, the break-even point was 224
      consultations a year, substantially below the actual utilization of
      telepsychiatry. Telepsychiatry appeared to result in increased access to
      community mental health services, suggesting future increased demand for these.
      From the perspective of health authorities and health professionals,
      telepsychiatry proved to be a useful and sustainable addition to existing mental
      health services.

PMID- 11331047
TI  - The use of e-mail by doctors in the West Midlands.
AB  - We surveyed the use of e-mail by doctors in the West Midlands. In addition to 224
      questionnaires distributed to doctors at three large hospitals, 300 general
      practitioners (GPs) selected randomly from a list of 711 were also sent
      questionnaires. There was a 60% response rate. Overall, 65% of the 314
      respondents used e-mail, but 84% of hospital doctors used email compared with 55%
      of GPs. E-mail was used mainly for communication with friends and family (92%)
      and work colleagues (61%), with only 7% using e-mail for transmitting clinical
      data and 3% to send or receive referrals. E-mail usage showed a significant trend
      with respect to age, being highest in the 20-29-year age group and lowest among
      those aged over 60 years. Over 60% of respondents felt that e-mail was not secure
      for the transfer of patient data. However, 90% felt that they would be using e
      mail in a clinical setting in five years' time. Despite the relatively high use
      of e-mail for social communication, work-related use by doctors was low.

PMID- 11331048
TI  - The effect of videoconferencing on the depth perception of observers.
AB  - The ability of the human eye to perceive depth was measured using a specially
      designed instrument. Visual acuity and both monocular and binocular stereoacuity
      were measured when viewing the instrument directly and via a videoconferencing
      link. Ten subjects with an average age of 32.5 years (range 24-50) took part in
      the study. The group mean visual acuity using both eyes under normal test
      conditions was -0.04 logMAR (Snellen 6/5) compared with 0.18 logMAR (Snellen
      6/10) for the video-link. The mean stereoacuity using both eyes was 37" (SD 18")
      under normal test conditions. When a videoconferencing link was used, the mean
      stereoacuity fell to 1218" (SD 1203") using one eye and to 1651" (SD 1419") using
      both eyes. The ability to perceive depth remotely via a video-link was
      significantly decreased compared with normal test conditions.

PMID- 11331049
TI  - A randomized controlled trial assessing the health economics of realtime
      teledermatology compared with conventional care: an urban versus rural
      perspective.
AB  - A randomized controlled trial was carried out to measure the cost-effectiveness
      of realtime teledermatology compared with conventional outpatient dermatology
      care for patients from urban and rural areas. One urban and one rural health
      centre were linked to a regional hospital in Northern Ireland by ISDN at 128
      kbit/s. Over two years, 274 patients required a hospital outpatient dermatology
      referral--126 patients (46%) were randomized to a telemedicine consultation and
      148 (54%) to a conventional hospital outpatient consultation. Of those seen by
      telemedicine, 61% were registered with an urban practice, compared with 71% of
      those seen conventionally. The clinical outcomes of the two types of consultation
      were similar--almost half the patients were managed after a single consultation
      with the dermatologist. The observed marginal cost per patient of the initial
      realtime teledermatology consultation was 52.85 Pounds for those in urban areas
      and 59.93 Pounds per patient for those from rural areas. The observed marginal
      cost of the initial conventional consultation was 47.13 Pounds for urban patients
      and 48.77 Pounds for rural patients. The total observed costs of teledermatology
      were higher than the costs of conventional care in both urban and rural areas,
      mainly because of the fixed equipment costs. Sensitivity analysis using a real
      world scenario showed that in urban areas the average costs of the telemedicine
      and conventional consultations were about equal, while in rural areas the average
      cost of the telemedicine consultation was less than that of the conventional
      consultation.

PMID- 11331050
TI  - Telecardiotocography in prenatal telemedicine.

PMID- 11331051
TI  - Development of a low-cost telepathology network in the UK National Health
      Service.

PMID- 11331052
TI  - Comparison of the effects of angiotensin converting-enzyme inhibitors and beta
      blockers on survival in elderly patients with reduced left ventricular function
      after myocardial infarction.
AB  - PURPOSE: Angiotensin converting-enzyme (ACE) inhibitors decrease mortality after
      myocardial infarction among patients with depressed left ventricular function.
      Beta blockers may also improve survival in these patients. We compared the
      relative effects of these agents on the survival of elderly patients with a left
      ventricular ejection fraction less than 40% after myocardial infarction. SUBJECTS
      AND METHODS: The Cooperative Cardiovascular Project collected data on patients
      aged 65 years and older who were admitted with myocardial infarction from April
      1994 to July 1995, including 20,902 with a measured left ventricular ejection
      fraction less than 40% before discharge. Using proportional hazard regression
      models that adjusted for patient characteristics and in-hospital treatments, we
      compared survival among patients discharged on ACE inhibitors, beta blockers,
      both medications, or neither medication. RESULTS: Among patients surviving
      hospitalization with reduced left ventricular function, 9,108 (44%) were
      discharged on ACE inhibitors, 2,613 (13%) on beta blockers, 3,309 (16%) on both
      medications, and 5,872 (28%) on neither medication. Patients treated with ACE
      inhibitors were more likely to have a prior diagnosis of heart failure and less
      likely to have undergone revascularization, whereas those treated with beta
      blockers were more often treated with thrombolytic therapy and aspirin. Patients
      treated with ACE inhibitors [hazard ratio (HR = 0.80), 0.80; 95% confidence
      interval (CI), 0.73 to 0.87] or beta blockers (HR = 0.76, 0.76; 95% CI, 0.64 to
      0.90) had lower adjusted 1-year mortality than those who were not treated with
      either medication. The combination of both medications was associated with
      additional benefit (HR = 0.68, 0.68; 95% CI, 0.59 to 0.80). The relative benefit
      of each medication was greatest among patients with an ejection fraction less
      than 30%, a serum creatinine level 2.0 mg/dL or greater, or both. To prevent a
      death within a year, the number of patients who needed to be treated with both
      medications varied from 5 to 15, depending on ejection fraction and renal
      function. CONCLUSION: ACE inhibitors and beta blockers were associated with
      similar improvements in survival among elderly patients with reduced left
      ventricular ejection fraction after myocardial infarction. Our results suggest
      that patients who can tolerate both medications gain additional benefit from the
      combination.

PMID- 11331053
TI  - The natural history of immunoglobulin a nephropathy among patients with hematuria
      and minimal proteinuria.
AB  - PURPOSE: To determine the natural history of immunoglobulin (Ig) A nephropathy
      among patients who presented with hematuria and minimal proteinuria, and factors
      associated with the development of adverse clinical events, such as proteinuria.
      SUBJECTS AND METHODS: In Hong Kong, all patients who present with isolated
      hematuria are referred for renal biopsy after urologic diseases are ruled out. We
      reviewed the clinical course of 72 consecutive patients with histologically
      confirmed IgA nephropathy who presented with hematuria and minimal proteinuria
      (0.4 g/day or less). All patients were normotensive and had normal renal function
      at presentation. Adverse events were defined as proteinuria greater than 1 g per
      day, hypertension, or impaired renal function (serum creatinine level 120
      micromol/L or estimated creatinine clearance < 70 mL per minute). RESULTS: The
      mean (+/- SD) age at presentation was 27 +/- 8 years; 56 (78%) were female. Nine
      patients (13%) had grade 2 histologic lesions. During a median follow-up of 7
      years, 32 patients (44%) developed adverse events: 24 (33%) developed proteinuria
      of 1 g per day or more, 19 (26%) became hypertensive, and 5 (7%) developed
      impaired renal function. Another 30 patients (42%) had persistently abnormal
      urinalysis examinations. Only 10 patients (14%) had complete resolution of
      hematuria. The median time for progression from proteinuria (> l g/day) to renal
      impairment was 84 months (range 56 to 132). In a multivariate analysis, age at
      presentation (relative risk [RR] per 10 years of age = 2.0; 95% confidence
      interval [CI], 1.2 to 3.4) and histologic grade (grade 2 versus grade 1, RR =
      4.5; 95% CI, 1.7 to 12) were independent predictors of developing an adverse
      event. CONCLUSIONS: IgA nephropathy that presents with hematuria and minimal
      proteinuria is usually a progressive disease. Life-long follow-up with regular
      monitoring of blood pressure and proteinuria is recommended.

PMID- 11331054
TI  - Life-threatening hyperkalemia during combined therapy with angiotensin-converting
      enzyme inhibitors and spironolactone: an analysis of 25 cases.
AB  - PURPOSE: The beneficial effects of spironolactone are additive to those of ACE
      inhibitors among patients with heart failure and/or hypertension; however, it is
      essential to identify patients prone to develop serious hyperkalemia during
      combined treatment and to evaluate the associated morbidity and mortality.
      SUBJECTS AND METHODS: We studied 25 patients treated with ACE inhibitors and
      spironolactone who were admitted to the emergency room with a serum potassium
      level > 6 mmol/L. Patients were followed up for at least one month after
      admission. RESULTS: The mean age of the patients (11 males, 14 females) was 74 +/
      13 years. Five patients were diabetics. On admission, the serum potassium was
      7.7 +/- 0.7 mmol/L and the serum creatinine was 3.8 +/- 1.8 mg/dL; these values
      were significantly higher than the most recent follow-up laboratory measurements
      (4.6 +/- 0.5 mmol/L and 1.9 +/- 1.2 mg/dL, respectively) obtained at 13 +/- 5
      weeks before admission. The arterial pH on admission was 7.3 +/- 0.1 and the
      plasma bicarbonate was 18 +/- 5 mmol/L. The main causes for acute renal failure
      were dehydration (n = 12) and worsening heart failure (n = 9). The mean daily
      dose of spironolactone was 57 +/- 32 mg and 12 patients were concomitantly
      treated with other drugs that may cause hyperkalemia. Two patients died, and 2
      patients were resuscitated but survived. Hemodialysis was necessary in 17
      patients; 12 patients were admitted to the intensive care unit. The mean duration
      of hospitalization was 12 +/- 6 days. Two patients needed to be started on
      maintenance hemodialysis therapy. CONCLUSION: A combination of ACE inhibitors and
      spironolactone should be considered with caution and monitored closely in
      patients with renal insufficiency, diabetes, older age, worsening heart failure,
      a risk for dehydration, and in combination with other medications that may cause
      hyperkalemia. A daily spironolactone dose of 25 mg should not be exceeded.

PMID- 11331055
TI  - Effects of hormone replacement therapy on clinical fractures and height loss: The
      Heart and Estrogen/Progestin Replacement Study (HERS).
AB  - PURPOSE: To determine if estrogen plus progestin reduces the incidence of
      fractures or height loss in postmenopausal women with coronary disease. SUBJECTS
      AND METHODS: We enrolled 2,763 postmenopausal women with coronary disease and
      with an intact uterus into the Heart Estrogen/progestin Replacement Study, a
      randomized double-blind, placebo-controlled secondary prevention trial of
      cardiovascular disease. Radiographically documented clinical fractures were a
      prespecified secondary endpoint. Height loss was used as a surrogate for
      vertebral fractures. The average age of the women was 66.7 +/- 6.7 years, and
      fewer than 15% of the women had osteoporosis based on their bone density. Women
      were randomly assigned to either 0.625 mg of conjugated equine estrogens plus 2.5
      mg of medroxyprogesterone acetate in 1 tablet daily (n = 1,380) or placebo (n =
      1,383). Follow-up averaged 4.1 years; 82% of those assigned to hormone treatment
      were taking it at the end of 1 year, and 64% at the end of the study. RESULTS:
      During 10,554 person years of follow-up, 286 women experienced a fracture: 138 in
      the treatment group (26.3 per 1,000 person years) and 148 in the placebo group
      (28.0 per 1,000 person years); relative hazard, 0.94; 95% confidence interval 0.8
      to 1.2, P = 0.61). These included 58 wrist fractures (1.01; 0.6 to 1.7); 27 hip
      fractures (1.09; 0.5 to 2.3); 32 spine fractures (0.69; 0.3 to 1.4), and 192
      other fractures (0.91; 0.7 to 1.2). There was no difference in average height
      loss between the treatment and placebo groups or in the percent of women who lost
      more than 2 cm in height: 10.6% in the treatment group and 12.1% in the placebo
      group. CONCLUSIONS: There was no evidence of a reduction in the incidence of
      fractures or rate of height loss in older women not selected for osteoporosis.
      Randomized studies are needed to clarify the effect of hormone replacement
      therapy on fracture risk among women with and without osteoporosis.

PMID- 11331056
TI  - Decreased mortality after implementation of a treatment guideline for community
      acquired pneumonia.
AB  - PURPOSE: We developed a pneumonia guideline at Intermountain Health Care that
      included admission decision support and recommendations for antibiotic timing and
      selection, based on the 1993 American Thoracic Society guideline. We hypothesized
      that guideline implementation would decrease mortality. SUBJECTS AND METHODS: We
      included all immunocompetent patients > 65 years with community-acquired
      pneumonia from 1993 through 1997 in Utah; nursing home patients were excluded. We
      compared 30-day mortality rates among patients before and after the guideline was
      implemented, as well as among patients treated by physicians who did not
      participate in the guideline program. RESULTS: We observed 28,661 cases of
      pneumonia, including 7,719 (27%) that resulted in hospital admission. Thirty-day
      mortality was 13.4% (1,037 of 7,719) among admitted patients and 6.3% (1,801 of
      28,661) overall. Mortality rates (both overall and among admitted patients) were
      similar among patients of physicians affiliated and not affiliated with
      Intermountain Health Care before the guideline was implemented. For episodes that
      resulted in hospital admission after guideline implementation, 30-day mortality
      was 11.0% among patients treated by Intermountain Health Care-affiliated
      physicians compared with 14.2% for other Utah physicians. Analysis that adjusted
      by logistic regression for age, sex, rural versus urban residences, and year
      confirmed that 30-day mortality was lower among admitted patients who were
      treated by Intermountain Health Care-affiliated physicians (odds ratio [OR]:
      0.69; 95% confidence interval [CI]: 0.49 to 0.97; P = 0.04) and was somewhat
      lower among all pneumonia patients (OR: 0.81; 95% CI: 0.63 to 1.03; P = 0.08).
      CONCLUSION: Implementation of a pneumonia practice guideline in the Intermountain
      Health Care system was associated with a reduction in 30-day mortality among
      elderly patients with pneumonia.

PMID- 11331057
TI  - Outpatient treatment of deep venous thrombosis in diverse inner-city patients.
AB  - PURPOSE: We sought to describe the development and outcomes of a hospital-based
      program designed to provide safe and effective outpatient treatment to a diverse
      group of patients with acute deep venous thrombosis. METHODS: Patients enrolled
      in the program were usually discharged on the day of or the day after
      presentation. Low- molecular-weight heparin was administered for a minimum of 5
      days and warfarin was given for a minimum of 3 months. The hospital provided low
      molecular-weight heparin free of charge to patients. Patients received daily home
      nursing visits to monitor the prothrombin time, assess compliance, and detect
      complications. The inpatient and outpatient records of the first 89 consecutive
      patients enrolled in the program were reviewed. Patients were observed for a 3
      month period after enrollment. RESULTS: The median length of stay was 1 day. Low
      molecular-weight heparin was administered for a mean (+/- standard deviation
      [SD]) of 4.7 +/- 2.4 days at home. Recurrent thromboembolism was noted in 1
      patient (1%), major bleeding in 2 patients (2%), and minor bleeding in 2 patients
      (2%). No patients died or developed thrombocytopenia. Assuming that patients
      would have been hospitalized for the duration of treatment with low-molecular
      weight heparin, the program eliminated a mean of 4.7 days of hospitalization,
      with an estimated reduction of $1,645 in total health care costs per patient.
      CONCLUSION: This hospital-based program to provide outpatient treatment of deep
      venous thrombosis to a diverse group of inner-city patients achieved a low
      incidence of adverse events and substantial health care cost savings. Specific
      strategies, including providing low-molecular-weight heparin free of charge and
      daily home nursing visits, can be utilized to facilitate access to outpatient
      treatment and ensure high-quality care.

PMID- 11331058
TI  - Key challenges confronting internal medicine in the early twenty-first century.

PMID- 11331059
TI  - Formulating clinical strategies for angiotensin antagonism: a review of
      preclinical and clinical studies.
AB  - Extensive animal studies and a growing number of human clinical trials have now
      definitively demonstrated the central role of the renin-angiotensin-aldosterone
      system in the expression and modulation of cardiovascular disease. In contrast to
      the original hypothesis, the benefits of angiotensin antagonism do not emanate
      from the antihypertensive effect alone. Subsequent extensive investigations of
      angiotensin blockade suggest that the benefits of this approach may also result
      from the pharmacologic alteration of endothelial cell function and the ensuing
      changes in the biology of the vasculature. The more recent availability of direct
      antagonists of the AT(1) angiotensin receptor has introduced an element of doubt
      into this realm of clinical decision making. The receptor antagonists and the
      more widely studied converting-enzyme inhibitors share many endpoint attributes.
      Nevertheless, the partially overlapping mechanisms of action for the two classes
      of angiotensin antagonists confer distinct pharmacologic properties, including
      side effect profiles, mechanisms of action, and theoretic salutary effects upon
      the expression of cardiovascular disease. The current review will attempt to
      contrast the biology of angiotensin converting-enzyme inhibition with angiotensin
      II receptor antagonism. A discussion of the differential effects of these drug
      classes on endothelial cell function and on the modulation of vascular disease
      will be utilized to provide a theoretic framework for clinical decision making
      and therapeutics.

PMID- 11331060
TI  - Prospective studies of the safety of acupuncture: a systematic review.
AB  - PURPOSE: The objective of this review was to determine the incidence of adverse
      events associated with acupuncture. SUBJECTS AND METHODS: A search for
      prospective surveys of the safety of acupuncture was conducted using computerized
      databases (Medline, Embase, the Cochrane Library, and CISCOM), inquiries to
      acupuncture organizations, and our own files. Data on sample, size, types of
      patients duration of study, types of acupuncture, definition of adverse events,
      method of evaluation, and findings were extracted systematically from the
      retrieved reports. RESULTS: Nine surveys were located and included in the review.
      Their results were not uniform. The most common adverse events were needle pain
      (1% to 45%) from treatments, tiredness (2% to 41%), and bleeding (0.03% to 38%).
      Feelings of faintness and syncope were uncommon, with an incidence of 0% to 0.3%.
      Feelings of relaxation were reported by as many as 86% of patients. Pneumothorax
      was rare, occurring only twice in nearly a quarter of a million treatments.
      CONCLUSIONS: Although the incidence of minor adverse events associated with
      acupuncture may be considerable, serious adverse events are rare. Those
      responsible for establishing competence in acupuncture should consider how to
      reduce these risks.

PMID- 11331061
TI  - Association of tumor necrosis factor-2 allele with plasma tumor necrosis factor
      alpha levels and mortality from septic shock.

PMID- 11331062
TI  - Hypertriglyceridemia and other factors associated with plasma viscosity.

PMID- 11331063
TI  - Diffuse non-hydrostatic, non-hypooncotic edema in autoimmune lupus-like
      disorders.

PMID- 11331064
TI  - Medical therapy for coronary artery disease works, even (especially) in the real
      world.

PMID- 11331065
TI  - Immunoglobulin a nephropathy with mild renal lesions: a call in the forest for
      physicians and nephrologists.

PMID- 11331066
TI  - Heparin therapy for deep vein thrombosis: from hospital to home.

PMID- 11331067
TI  - Internal medicine: at the nexus of the health care system in responding to the
      demographic imperative of an aging population.

PMID- 11331068
TI  - Ggamma-like (GGL) domains: new frontiers in G-protein signaling and beta
      propeller scaffolding.
AB  - The standard model of signal transduction from G-protein-coupled receptors
      (GPCRs) involves guanine nucleotide cycling by a heterotrimeric G-protein
      assembly composed of Galpha, Gbeta, and Ggamma subunits. The WD-repeat beta
      propeller protein Gbeta and the alpha-helical, isoprenylated polypeptide Ggamma
      are considered obligate dimerization partners; moreover, conventional Gbetagamma
      heterodimers are considered essential to the functional coupling of Galpha
      subunits to receptors. However, our recent discovery of a Gbeta5 binding site
      (the Ggamma-like or "GGL" domain) within several regulators of G-protein
      signaling (RGS) proteins revealed the potential for functional GPCR/Galpha
      coupling in the absence of a conventional Ggamma subunit. In addition, we posit
      that the interaction between Gbeta5 isoforms and the GGL domains of RGS proteins
      represents a general mode of binding between beta-propeller proteins and their
      partners, extending beyond the realm of G-protein-linked signal transduction.

PMID- 11331069
TI  - Protein kinase C-mediated down-regulation of MDR3 mRNA expression in Chang liver
      cells.
AB  - MDR3 is a phospholipid translocator homologous to MDR1 P-glycoprotein. MDR3
      localizes to the canalicular membrane and contributes to the secretion of bile.
      To elucidate the role of protein kinase C in the regulation of MDR3 gene
      expression, we investigated the effect of phorbol 12-myristate 13-acetate (PMA)
      on the level of MDR3 mRNA in human Chang liver cells by a reverse transcription
      polymerase chain reaction method. The steady-state expression of MDR3 mRNA was
      decreased by PMA after treatment for 8-20 hr and at concentrations of 1-100 nM.
      PMA also decreased the doxorubicin-induced expression of MDR3 mRNA. 4alpha
      Phorbol 12,13-didecanoate, a negative control compound, did not decrease the
      expression at these concentrations. The down-regulatory effect of PMA was
      partially suppressed by the protein kinase C inhibitors 2-[1-(3
      dimethylaminopropyl)-1H-indol-3-yl]-3-(1H-indol-3-yl)maleimide (GF109203X) and
      calphostin C. Furthermore, cycloheximide, a protein synthesis inhibitor,
      antagonized the effect of PMA. From these results, it was suggested that the
      level of MDR3 mRNA was negatively regulated by a protein kinase C- and protein
      synthesis-dependent system and that the system regulated both the stable and
      inducible expression of MDR3 mRNA.

PMID- 11331070
TI  - Involvement of all-trans-retinoic acid in the breakdown of retinoic acid
      receptors alpha and gamma through proteasomes in MCF-7 human breast cancer cells.
AB  - Most studies have reported an up-regulation of retinoic acid receptor (RAR) mRNA
      expression by all-trans retinoic acid (RA). We aimed to study the effect of RA on
      RAR protein levels in MCF-7 human breast cancer cells. Incubation of these cells
      with 10(-6) M RA induced a rapid breakdown of both RARalpha and RARgamma in spite
      of the accumulation of their mRNAs. Proteasome specific inhibitors blocked the RA
      induced breakdown of RARs. Furthermore, RA enhanced the formation of the complex
      between RARalpha and ubiquitin in a concentration- and time-dependent manner,
      suggesting the involvement of ubiquitin and proteasome in this reaction. Retinoid
      X receptor alpha (RXRalpha) was also decreased, albeit to a lesser extent, in RA
      treated cells. Use of synthetic receptor agonists and antagonists clearly showed
      that the effect of the retinoid on the breakdown of the retinoid receptors is
      receptor-ligand agonist-dependent and blunted by the antagonist. An
      electrophoretic mobility shift assay, using nuclear extracts from RA-treated
      cells, showed that a reduction in complex formation with hormone response
      elements correlated with the reduction of RAR and RXR protein. These data suggest
      that RA induces the breakdown of RARs through a process involving ubiquitination
      and that this phenomenon causes a reduction in the formation of DNA-receptor
      complexes.

PMID- 11331071
TI  - Cannabinoid-induced alterations in brain disposition of drugs of abuse.
AB  - Marijuana contains a complex mixture of compounds including tetrahydrocannabinol
      (THC), the major psychoactive constituent, and cannabidiol (CBD), a
      nonpsychoactive constituent. We have shown previously that CBD pretreatment of
      mice increases brain levels of THC and have now further characterized this effect
      and determined whether the brain pharmacokinetics of other drugs are also
      affected. CBD pretreatment of mice (30-60 min) increased brain levels of THC
      nearly 3-fold, whereas CBD co-administration did not. Because marijuana is often
      consumed with other drugs, the influence of cannabinoids on the brain levels of
      several other drugs of abuse was also determined. CBD pretreatment of mice
      increased brain levels (2- to 4-fold) of subsequently administered cocaine as
      well as phencyclidine (PCP). Although CBD pretreatment increased blood and brain
      levels of cocaine comparably, blood levels of PCP were only modestly elevated (up
      to 50%). Behavioral tests indicated that the CBD-mediated increases in the brain
      levels of THC, cocaine, and PCP correlated with increased pharmacological
      responses. Pretreatment with THC instead of CBD could similarly increase brain
      levels of cocaine, PCP, and CBD, although with a lower potency than CBD. On the
      other hand, pretreatment of mice with CBD had no effect on the brain levels of
      several other drugs of abuse including morphine, methadone, or
      methylenedioxyphenyl-methamphetamine. These findings demonstrate that
      cannabinoids can increase the brain concentrations and pharmacological actions of
      several other drugs of abuse, thereby providing a biochemical basis for the
      common practice of using marijuana concurrently with such drugs.

PMID- 11331072
TI  - Comparative pharmacological studies of melatonin receptors: MT1, MT2 and MT3/QR2.
      Tissue distribution of MT3/QR2 .
AB  - The neurohormone melatonin is the central switch of the circadian rhythm and
      presumably exerts its activities through a series of receptors among which MT1
      and MT2 have been widely studied. The third binding site of melatonin, MT3, has
      been recently characterized as a melatonin-sensitive form of the quinone
      reductase 2 (QR2, EC 1.6.99.2). In the present work, we showed that the binding
      of melatonin at MT3/QR2 was better described with 2-[125I]-iodomethoxy
      carbonylamino-N-acetyltryptamine (2-[125I]-I-MCA-NAT) and, most importantly, that
      it was measurable at 20 degrees while it has been initially described and
      thoroughly studied using 2-[125I]-iodomelatonin at 4 degrees. Under these novel
      conditions, binding to MT3 could be traced without cross-reactivity with MT1 and
      MT2 receptors and, moreover, under conditions similar to those used to measure
      MT3/QR2 catalytic activity. The pharmacology established here on hamster kidney
      samples using the reference compounds remained essentially as already described
      using other experimental conditions. A new series of compounds with nanomolar
      affinity for the MT3 binding site and a high MT3 selectivity versus MT1 and MT2
      is reported. In addition, we further document the MT3/QR2 binding site by
      demonstrating that it was widely distributed among mammals, although inter
      species and inter-tissues differences exist. The present report details new
      experimental conditions for the pharmacological study of melatonin-sensitive QR2
      isoforms, and suggests that, in addition to an already demonstrated inter-species
      difference, inter-tissues differences in QR2 sensitivity to melatonin may exist
      in primates and, therefore, represent an original and interesting route of
      investigation on the effect of melatonin on MT3/QR2.

PMID- 11331073
TI  - Cytotoxic action of methylglyoxal on insulin-secreting cells.
AB  - Methylglyoxal is a spontaneous product of glucose metabolism which is known to
      have cytotoxic actions and to be present in raised concentrations in
      hyperglycaemia. It could therefore play an important role in glucose toxicity. We
      have investigated the cytotoxic effects of methylglyoxal on insulin-secreting
      cells, which are particularly sensitive to glucose toxicity. Methylglyoxal caused
      a concentration-dependent increase in the number of apoptotic RINm5F cells within
      4-6 hours. A similar effect was observed with rat pancreatic beta-cells. tert
      butylglyoxal, which is a poor substrate for the glyoxalase pathway, exerted a
      similar, though more potent apoptotic action. Dexamethasone and NaF were also
      found to induce apoptosis in RINm5F cells. Flow cytometric analysis suggested a
      degree of necrosis in addition to apoptosis resulting from treatment with
      methylglyoxal. The cytotoxic effect of methylglyoxal could contribute towards
      glucose toxicity in insulin-secreting cells.

PMID- 11331074
TI  - Resistance of human multidrug resistance-associated protein 1-overexpressing lung
      tumor cells to the anticancer drug arsenic trioxide.
AB  - The human multidrug-resistance protein (MRP1) confers resistance to some heavy
      metals such as arsenic and antimony, mainly through mediating an increased
      cellular efflux of metal. However, it was recently suggested that arsenic, used
      under its trioxide derivative form as anticancer drug, is not handled by MRP1.
      The aim of the present study was to test this hypothesis in MRP1-overexpressing
      human lung tumor GLC4/Sb30 cells. Using the cytotoxicity MTT assay, GLC4/Sb30
      cells were found to be 10.8-fold more resistant to arsenic trioxide (As2O3) than
      parental GLC4 cells. MK571, a potent inhibitor of MRP1 activity, almost totally
      reversed resistance of GLC4/Sb30 cells, but did not alter the sensitivity of GLC4
      cells. Moreover, As2O3-loaded GLC4/Sb30 cells poorly accumulated arsenic through
      an increased MK571-sensitive efflux of metal. Finally, depletion of cellular
      glutathione levels in buthionine sulfoximine-treated GLC4/Sb30 cells was found to
      result in increased accumulation and reduced efflux of arsenic in cells exposed
      to As2O3, outlining the glutathione-dependence of MRP1-mediated transport of the
      metal. These results indicate that MRP1 overexpression in human tumor cells can
      confer resistance to As2O3, which may limit the clinical use of this anticancer
      drug for treatment of MRP1-positive tumors.

PMID- 11331075
TI  - Modulation by LY335979 of P-glycoprotein function in multidrug-resistant cell
      lines and human natural killer cells.
AB  - Resistance to chemotherapy by some human tumors may be due to overexpression of
      membrane-associated transport proteins. The best characterized of these is the
      multidrug resistance (MDR) transporter, P-glycoprotein (Pgp). The aim of this
      study was to measure the inhibitory effects of a potent new MDR modulator, (2R)
      anti-5-(3-[4-(10,11-difluoromethanodibenzo-suber-5-yl) piperazin-1-yl]-2
      hydroxypropoxy)quinoline trihydrochloride (LY335979), in the drug-resistant cell
      line HL60/VCR and in normal, human CD56(+) lymphocytes. We used flow cytometric
      methods to detect the accumulation of rhodamine 123 and daunorubicin, fluorescent
      MDR substrates, in these cells. Our results indicate that LY335979 was 500-1500
      times more potent than cyclosporin A or verapamil in restoring Pgp substrate
      accumulation in the MDR cell line HL60/VCR. Moreover, LY335979 could effectively
      block Pgp function on isolated CD56(+) lymphocytes (IC(50) = 1.2 nM) or CD56(+)
      lymphocytes in whole blood (IC(50) = 174 nM). We conclude that LY335979 is among
      the most potent Pgp inhibitors described and that it maintains significant
      potency in whole-human blood. These latter findings are important for
      establishing the dosing regimens of LY335979 for future clinical studies.

PMID- 11331076
TI  - Collateral sensitivity to gemcitabine (2',2'-difluorodeoxycytidine) and cytosine
      arabinoside of daunorubicin- and VM-26-resistant variants of human small cell
      lung cancer cell lines.
AB  - Multidrug resistance (MDR), characterized by a cross-resistance to many natural
      toxin-related compounds, may be caused either by overexpression of a drug efflux
      pump such as P-glycoprotein, (P-gP), multidrug resistance proteins MRP1-3, or
      BCRP/MXR or, in the case of DNA topoisomerase II active drugs, by a decrease in
      the enzymatic activity of the target molecule termed altered topoisomerase MDR
      (at-MDR). However, human small cell lung carcinoma (SCLC) cell lines showed a
      collateral sensitivity to 2',2'-difluorodeoxycytidine (gemcitabine, dFdC) and 1
      beta-D-arabinofuranosylcytosine (ara-C). H69/DAU, a daunorubicin (DAU)-resistant
      variant of H69 with a P-gP overexpression, and NYH/VM, a VM-26 (teniposide)
      resistant variant of NYH with an at-MDR, were both 2-fold more sensitive to
      gemcitabine and 7- and 2-fold more sensitive to ara-C, respectively. MDR variants
      had a 4.3- and 2.0-fold increased activity of deoxycytidine kinase (dCK),
      respectively. dCK catalyzes the first rate-limiting activation step of both
      gemcitabine and ara-C. In addition, deoxycytidine deaminase, responsible for
      inactivation of dFdC and ara-C, was 9.0-fold lower in H69/DAU cells. The level of
      thymidine kinase 2, a mitochondrial enzyme that can also phosphorylate
      deoxycytidine and gemcitabine, was not significantly different between the
      variants. These differences most likely caused an increased accumulation of the
      active metabolites (dFdCTP, 2.1- and 1.6-fold in NYH/VM and H69/DAU cells,
      respectively) and of ara-CTP (1.3-fold in NYH/VM cells). Ara-CTP accumulation was
      not detectable in either H69 variant. The pools of all ribonucleoside and
      deoxyribonucleoside triphosphates were at least 3- to 4-fold higher in the NYH
      variants compared to the H69 variants; for dCTP and dGTP this difference was even
      larger. The higher ribonucleotide pools might explain the >10-fold higher
      accumulation of dFdCTP in NYH compared to H69 variants. Since dCTP is low, H69
      cells might not need a high ara-CTP accumulation to inhibit DNA polymerase. This
      might be related to the lack of ara-CTP in H69 variants. In addition, the
      increased CTP, ATP, and UTP pools in the MDR variants might explain the increased
      ara-CTP and dFdCTP accumulation. In conclusion, the MDR variants of the human
      SCLC cell lines were collaterally sensitive due to an increased dCK activity, and
      consequently an increased ara-CTP and dFdCTP accumulation.

PMID- 11331077
TI  - The effect of a paracetamol and morphine combination on dynorphin A levels in the
      rat brain.
AB  - The purpose of this study was to find out whether the combination of inactive
      doses of paracetamol (PARA) and morphine was able to change dynorphin (DYN) A
      levels, evaluated by radioimmunoassay, and whether naloxone or [(-)-2-(3
      furylmethyl)-normetazocine] (MR 2266), a kappa-opioid antagonist, modifies or
      prevents the activity of this combination on nociception and on DYN levels. The
      work was suggested by our previous findings which demonstrated that inactive
      doses of PARA and morphine, when given in combination, share an antinociceptive
      effect, and that PARA, at antinociceptive doses, decreases DYN levels in the
      frontal cortex, thus indicating a selective action within the CNS. Our present
      results demonstrate that the combination of inactive doses of PARA (100 mg/kg)
      and morphine (3 mg/kg) is just as effective in decreasing the levels of DYN A as
      full antinociceptive doses of PARA or morphine alone in the frontal cortex of the
      rat. The values, expressed in pmol/g tissue, were: control = 2.83 +/- 0.20;
      paracetamol (100) = 2.60 +/- 0.23; morphine (3) = 2.73 +/- 0.24; paracetamol +
      morphine = 1.34 + 0.16 (P < 0.05). The decrease was partially antagonised by MR
      2266, but not by naloxone, suggesting that the activity of PARA and morphine in
      combination on DYN A levels could be mediated, at least in part, through kappa
      receptors, although other systems may be involved. On the other hand, both
      naloxone and MR 2266 prevented the antinociceptive effect of the combination in
      the hot plate test. All our experimental data suggest that PARA and morphine in
      combination exert their antinociceptive effect through the opioidergic system,
      which in turn may cause a decrease in DYN levels in the CNS of the rat.

PMID- 11331078
TI  - Wogonin, baicalin, and baicalein inhibition of inducible nitric oxide synthase
      and cyclooxygenase-2 gene expressions induced by nitric oxide synthase inhibitors
      and lipopolysaccharide.
AB  - We previously reported that oroxylin A, a polyphenolic compound, was a potent
      inhibitor of lipopolysaccharide (LPS)-induced expression of inducible nitric
      oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). In the present study, three
      oroxylin A structurally related polyphenols isolated from the Chinese herb Huang
      Qui, namely baicalin, baicalein, and wogonin, were examined for their effects on
      LPS-induced nitric oxide (NO) production and iNOS and COX-2 gene expressions in
      RAW 264.7 macrophages. The results indicated that these three polyphenolic
      compounds inhibited LPS-induced NO production in a concentration-dependent manner
      without a notable cytotoxic effect on these cells. The decrease in NO production
      was in parallel with the inhibition by these polyphenolic compounds of LPS
      induced iNOS gene expression. However, these three compounds did not directly
      affect iNOS enzyme activity. In addition, wogonin, but not baicalin or baicalein,
      inhibited LPS-induced prostaglandin E2 (PGE2) production and COX-2 gene
      expression without affecting COX-2 enzyme activity. Furthermore, N-nitro-L
      arginine (NLA) and N-nitro-L-arginine methyl ester (L-NAME) pretreatment enhanced
      LPS-induced iNOS (but not COX-2) protein expression, which was inhibited by these
      three polyphenolic compounds. Wogonin, but not baicalin or baicalein, similarly
      inhibited PGE2 production and COX-2 protein expression in NLA/LPS or L-NAME/LPS
      co-treated RAW 264.7 cells. These results indicated that co-treatment with NOS
      inhibitors and polyphenolic compounds such as wogonin effectively blocks acute
      production of NO and, at the same time, inhibits expression of iNOS and COX-2
      genes.

PMID- 11331079
TI  - Selective inhibition of interleukin-8-induced neutrophil chemotaxis by ketoprofen
      isomers.
AB  - Although it is commonly accepted that the anti-inflammatory effect of
      nonsteroidal anti-inflammatory drugs (NSAIDs) is mainly associated to their
      ability to inhibit the cyclooxygenase (COX) enzyme system, several results
      indicate that non-COX mechanisms could be important in the therapeutical effect
      of these drugs. The aim of this study was to define if NSAIDs could exert, at
      least in part, their anti-inflammatory effect by inhibiting the activities of
      human polymorphonuclear leukocytes (PMNs) triggered by chemotactic stimuli and,
      if so, to understand the relationship of this effect with COX inhibition. A
      unique opportunity to dissociate the inhibition of prostaglandin (PG) synthesis
      from other therapeutical properties of NSAIDs is constituted by ketoprofen
      isomers being the S-isomer 100 time more potent than R-isomer on COX inhibition.
      Our results show that R- and S-ketoprofen, independently of their potency as PG
      inhibitors, proved very efficacious in selective inhibition of interleukin-8 (IL
      8) chemotaxis. Inhibition of IL-8 chemotaxis was not restricted to ketoprofen
      isomer as it could be observed also with drugs belonging to different classes of
      NSAIDs and it was obtained at drug concentration superimposable to plasma levels
      after therapeutic administration in patients. Reduction of IL-8 migration by
      ketoprofen isomers was paralleled by selective inhibition of PMN response in
      terms of intracellular calcium concentration ([Ca(2+)]i) increase and
      extracellular signal regulated kinase(ERK)-2 activation, two intracellular
      mediators reported to be critical for PMN activities. It is concluded that
      inhibition of IL-8 chemotaxis could represent a new clinical target for
      ketoprofen isomers and, in fact, contribute to the anti-inflammatory activity of
      NSAIDs.

PMID- 11331080
TI  - A mechanistic study of proliferation induced by Angelica sinensis in a normal
      gastric epithelial cell line.
AB  - It has been reported that an extract from Angelica sinensis mainly consisting of
      polysaccharides (95%) prevented ethanol- or indomethacin-induced gastric mucosal
      damage (Cho CH et al. Planta Med 2000;66:348-51). However, it is not known
      whether Angelica sinensis has a direct stimulatory effect on the healing of
      gastric mucosal lesions. To study the hypothesis that Angelica sinensis has a
      direct mucosal healing effect in rats and in isolated gastric epithelial cells,
      we assessed the wound repair in both animals and normal cell culture (RGM-1), as
      well as [3H]thymidine incorporation, ornithine decarboxylase (ODC) activity, and
      ODC protein and c-Myc protein expression after different treatments in RGM-1
      cells. We found that Angelica sinensis crude extract (ASCE) dose-dependently
      enhanced gastric ulcer healing in rats and promoted wound repair in RGM-1 cells.
      It also significantly stimulated [3H]thymidine incorporation and ODC activity in
      RGM-1 cells in a concentration-dependent manner. ODC and c-Myc protein expression
      was also increased as a result of this process. DL-alpha-difluoromethyl-ornithine
      repressed the [3H]thymidine incorporation and ODC activity induced by ASCE.
      Pretreatment with c-Myc antisense oligodeoxynucleotides blocked the stimulatory
      action of ASCE on [3H]thymidine incorporation and ODC protein expression. These
      data suggest that ASCE has a direct mucosal healing effect on gastric epithelial
      cells, while ODC and c-Myc are closely associated with this effect.

PMID- 11331081
TI  - Protective effect of carvedilol on chenodeoxycholate induction of the
      permeability transition pore.
AB  - Intracellular accumulation of toxic, hydrophobic bile acids has been proposed as
      one of the putative final common pathways leading to cholestatic liver injury.
      Furthermore, bile acids have been proposed as a causative factor for hepatic
      cardiomyopathy. Hepatic tissue concentrations of chenodeoxycholic acid (CDCA)
      during cholestasis are greater than those of other toxic bile acids. In the
      presence of calcium and phosphate, CDCA induced the permeability transition pore
      (PTP) in freshly isolated rat liver mitochondria. In this study, we evaluated the
      effects of carvedilol, a multirole cardioprotective compound, on CDCA-induced
      PTP. Mitochondrial membrane potential, osmotic swelling, and calcium fluxes were
      monitored. CDCA-induced PTP, characterized by membrane depolarization, release of
      matrix calcium, and osmotic swelling, was prevented by carvedilol. Under the same
      conditions, its hydroxylated analog BM-910228 did not reveal any protective
      effect. This finding reinforces carvedilol's therapeutic interest, because it may
      potentially prevent mitochondrial dysfunction associated with cardiomyopathy in
      the pathophysiology of cholestatic liver disease

PMID- 11331082
TI  - Reductions in neuronal and glial density characterize the dorsolateral prefrontal
      cortex in bipolar disorder.
AB  - BACKGROUND: Bipolar disorder (BPD) is a mental illness in which depression and
      mania typically alternate, and both phases can present with psychotic features.
      The symptomatology of BPD, therefore, resembles major depressive disorder (MDD)
      and schizophrenia (SCHZ), posing diagnostic dilemmas. Distinct alterations in
      cellular architecture of the dorsolateral prefrontal cortex distinguish SCHZ and
      MDD, whereas the cellular neuropathology of BPD has not been studied. METHODS:
      Dorsolateral prefrontal area 9 was analyzed using a three-dimensional
      morphometric method in postmortem brains from 10 BPD patients and 11 matched
      nonpsychiatric control subjects. RESULTS: Area 9 in BPD was characterized by
      reduced neuronal density in layer III (16%-22%) and reduced pyramidal cell
      density in layers III and V (17%-30%). A 19% reduction in glial density was found
      in sublayer IIIc coupled with enlargement and changes in shape of glial nuclei
      spanning multiple layers. CONCLUSIONS: The morphologic signature of BPD, i.e.,
      decreased neuronal and glial density in association with glial hypertrophy, is
      distinct from previously described elevations in neuronal density in SCHZ,
      instead resembling the reductions in cell density found in MDD. Thus, the
      neuropathologic distinctions between BPD and SCHZ are indicative of separate
      mental illnesses, each with a unique morphologic disturbance of specific neural
      circuits.

PMID- 11331083
TI  - Expression of the cAMP response element binding protein (CREB) in hippocampus
      produces an antidepressant effect.
AB  - BACKGROUND: Recent studies have demonstrated that chronic antidepressant
      treatment increases the expression of the cyclic amp (cAMP) response element
      binding protein (CREB) in rat hippocampus. The study presented here was conducted
      to determine if CREB is a relevant target that produces an antidepressant-like
      effect. METHODS: We employed the herpes simplex virus (HSV)-mediated gene
      transfer technique to overexpress CREB and determined its effect on the learned
      helplessness and forced swim tests, two established models used for
      pharmacological screening of antidepressant drugs. RESULTS: In the learned
      helplessness model, rats that received bilateral microinjection of HSV-CREB into
      the dentate gyrus showed significantly fewer escape failures in the subsequent
      conditioned avoidance test than those injected with control vector (HSV-LacZ). In
      contrast, microinjection of HSV-CREB in either the CA1 pyramidal cell layer of
      hippocampus or the prefrontal cortex did not produce an antidepressant response.
      In the forced swim test, CREB expression in the dentate gyrus resulted in a
      significantly shorter immobility time than those injected with HSV-LacZ.
      CONCLUSIONS: These results demonstrate that over-expression of CREB in
      hippocampus results in an antidepressant effect and suggest that CREB may serve
      as a potential molecular target for novel therapeutic agents.

PMID- 11331084
TI  - Exposure to the stressor environment prevents the temporal dissipation of
      behavioral depression/learned helplessness.
AB  - BACKGROUND: Exposure to uncontrollable stressors such as inescapable shock (IS)
      produces a set of behavioral changes such as poor escape learning that have been
      called behavioral depression and learned helplessness. This paradigm has been
      proposed to be a model of depression and of anxiety-related disorders such as
      posttraumatic stress disorder (PTSD). However, the behavioral changes persist for
      only a few days after the stressor, rendering the phenomenon questionable as a
      model. However, the original traumatic experience is re-experienced in PTSD and
      rumination occurs in depression. In a series of experiments we therefore sought
      to determine whether behavioral depression/learned helplessness could be made to
      endure by periodically "reminding" the subject of the original IS experience.
      METHODS: Rats exposed to IS were tested for escape learning at various times
      thereafter. In different experiments the subjects were exposed to the environment
      in which IS had occurred at differing points in the interval between IS and
      escape testing. RESULTS: Exposure to the environment in which IS had occurred
      prolonged the duration of behavioral depression/learned helplessness, and
      repeated exposures prolonged it indefinitely. This effect required exposure to
      the cues that had been present during IS (i.e., reminding) and was not duplicated
      by exposure to other stressors or stress environments. CONCLUSIONS: Behavioral
      depression/learned helplessness can be maintained over time by processes that may
      be similar to those occurring in depression and PTSD, thereby strengthening the
      possibility that this paradigm is indeed a reasonable model of these disorders.

PMID- 11331085
TI  - Cocaine-induced cerebral vasoconstriction differs as a function of sex and
      menstrual cycle phase.
AB  - BACKGROUND: Chronic cocaine abusing women experience fewer cerebral perfusion
      defects and less neuronal injury than men with comparable drug use histories.
      This study assessed whether a basis for this discrepancy is a sex difference in
      cocaine's acute cerebrovascular effects. METHODS: The subjects in this study were
      13 healthy and neurologically normal women, reporting occasional cocaine (mean
      13, range 1-40 lifetime cocaine exposures). All subjects were administered
      cocaine (0.4 mg/kg) intravenously, during both the follicular (days 3-8) and
      luteal (days 18-24) menstrual cycle phases. Dynamic susceptibility contrast
      magnetic resonance imaging assessments of relative global cerebral blood volume
      (CBV) changes were conducted on both study days, 10 min after cocaine
      administration. RESULTS: Cocaine did not alter CBV in follicular phase women, but
      reduced luteal phase CBV by 10%, indicative of vasoconstriction (analysis of
      variance [ANOVA], F = 5.1, p <.05). Postcocaine CBV was lower in men administered
      the drug via an identical protocol relative to follicular phase women (ANOVA, F =
      5.4, p <.04). Postcocaine CBV was also lower in the male referent group relative
      to luteal phase women, but this difference did not achieve statistical
      significance. No measurable sex or menstrual cycle phase differences in cocaine's
      cardiovascular effects were noted. CONCLUSIONS: These findings suggest both
      menstrual cycle phase and sex differences in cocaine's acute cerebrovascular
      effects, which may contribute to sex differences in the severity of brain
      dysfunction found in chronic cocaine abusers. These findings imply that gonadal
      steroids or the factors they modulate merit study as possible therapeutic agents
      for reducing cocaine-induced cerebrovascular disorders.

PMID- 11331086
TI  - Leptin: a modulator of alcohol craving?
AB  - BACKGROUND: Leptin has been shown to regulate food intake and energy expenditure.
      Because leptin acts via regulation of appetite, we studied the hypothesis that
      suggests leptin modulates craving for alcohol as well. METHODS: We studied leptin
      plasma concentrations (RIA) both in alcoholic subjects during inpatient
      detoxification (day 1: n = 78, day 14: n = 60) and in healthy control subjects (n
      = 30). To rule out interference with the activation of the HPA axis during
      alcohol withdrawal, we also evaluated cortisol plasma levels (RIA). RESULTS: We
      found plasma leptin and cortisol elevated at onset of withdrawal, decreasing
      significantly up to day 14. Leptin (and the body-mass corrected ratio leptin/BMI)
      was highly correlated with self-rated craving. No correlations of craving with
      cortisol and BMI were observed. CONCLUSIONS: We suggest that leptin may modulate
      withdrawal-induced craving in alcoholic subjects.

PMID- 11331087
TI  - Allopregnanolone levels and reactivity to mental stress in premenstrual dysphoric
      disorder.
AB  - BACKGROUND: This study was designed to examine basal and stress-induced levels of
      the neuroactive progesterone metabolite, allopregnanolone, in women with
      premenstrual dysphoric disorder (PMDD) and healthy control subjects. Also,
      because evidence suggests that allopregnanolone negatively modulates the
      hypothalamic-pituitary-adrenal axis, plasma cortisol levels were examined. An
      additional goal was to investigate the relationship between premenstrual symptom
      severity and luteal phase allopregnanolone levels. METHODS: Twenty-four women
      meeting prospective criteria for PMDD were compared with 12 controls during both
      the follicular and luteal phases of confirmed ovulatory cycles, counterbalancing
      phase at first testing. Plasma allopregnanolone and cortisol were sampled after
      an extended baseline period and again 17 min following the onset of mental
      stress. Owing to low follicular phase allopregnanolone levels, only luteal phase
      allopregnanolone and cortisol were analyzed. RESULTS: During the luteal phase,
      PMDD women had significantly greater allopregnanolone levels, coupled with
      significantly lower cortisol levels, during both baseline and mental stress.
      Moreover, significantly more controls (83%) showed the expected stress-induced
      increases in allopregnanolone compared with PMDD women (42%). Premenstrual
      dysphoric disorder women also exhibited a significantly greater
      allopregnanolone/progesterone ratio than control subjects, suggesting alterations
      in the metabolic pathways involved in the conversion of progesterone to
      allopregnanolone. Finally, PMDD women with greater levels of premenstrual anxiety
      and irritability had significantly reduced allopregnanolone levels in the luteal
      phase relative to less symptomatic PMDD women. No relationship between symptom
      severity and allopregnanolone was observed in controls. CONCLUSIONS: These
      results suggest dysregulation of allopregnanolone mechanisms in PMDD and that
      continued investigations into a potential pathophysiologic role of
      allopregnanolone in PMDD are warranted.

PMID- 11331088
TI  - Magnetization transfer of fluoxetine in the human brain using fluorine magnetic
      resonance spectroscopy.
AB  - Fluorine magnetic resonance spectroscopy ((19)F MRS) measurements of fluoxetine
      and metabolite concentration in the human brain underestimate true drug levels
      because of a bound, MRS-"invisible" pool of drug molecules. Magnetization
      transfer (MT) spectroscopy may be a useful technique for characterizing this
      bound pool of fluoxetine in the brain. Six subjects on consistent daily doses of
      fluoxetine underwent (19)F MT spectroscopy on a 1.5-T scanner using a train of
      three preparation pulses at -3000 Hz off resonance with 0.5 W of peak power
      deposition in tissue. One subject was scanned at multiple time points after
      initiation of drug therapy. Magnetization transfer signal contrast was quantified
      using VARPRO-based time domain fitting software. Magnetization transfer signal
      contrast was quantifiable with mean MT signal depression of 12.5% (SD = 5.0, n =
      6). An inverse relationship between brain concentration and the MT signal
      contrast of fluoxetine was found (r = -.82, Spearman coefficient =.007). This
      study is the first in vivo application of (19)F MT spectroscopy and the first to
      demonstrate a quantifiable MT effect for a psychotropic medication in the human
      brain. Findings suggest that fluoxetine is substantially bound in the brain and
      that individual differences, inversely related to brain concentration, can be
      detected in the magnitude of MT contrast.

PMID- 11331089
TI  - Medial orbital frontal lesions in late-onset depression.
AB  - BACKGROUND: Early studies using magnetic resonance (MR) imaging suggested that
      subcortical vascular changes are more prevalent in late-life depression and that
      they may play a role in the pathophysiology of depression. Studying the location
      of the lesion relative to the occurrence of depression could be critical in
      delineating the neuroanatomic substrates of depression. Our purpose was to
      characterize these lesions in terms of location by development of statistical
      parametric maps of lesions that differentiate patients from control subjects.
      METHODS: Magnetic resonance images were acquired on 88 elderly depressed subjects
      ("patients," unipolar major depression assessed using the Duke Depression
      Evaluation Schedule, age range 63-80 years) enrolled in the Duke University
      Clinical Research Center for the Study of Late-Life Depression and 47 age- and
      gender-matched nondepressed subjects ("control subjects"). The MR protocol
      includes a volumetric, dual-contrast fast spin-echo pulse sequence. A statistical
      parametric map was formed from a two-group t test to test for differences in
      lesion density between patients and control subjects. Additional testing was
      performed to evaluate whether there were regions that correlated with the
      severity of depression using the 17-item Hamilton Depression rating. RESULTS: The
      statistical parametric mapping analysis between groups showed two major regions
      of increased lesion density in the patients in the medial orbital prefrontal
      white matter. Severity of depression among depressed patients was correlated with
      lesions in the medial orbital region. CONCLUSIONS: This study supports recent
      evidence implicating the medial orbital frontal cortex in depression.

PMID- 11331090
TI  - The question of PANDAS in adults.
AB  - BACKGROUND: Pediatric autoimmune neuropsychiatric disorders associated with
      streptococcal infections (PANDAS) are a well-defined cause of obsessive
      compulsive disorder in children. However, they have not been described or fully
      investigated in adults newly diagnosed with obsessive-compulsive disorder.
      METHODS: We describe an adult with onset of obsessive-compulsive disorder at 25
      years of age after a severe antibiotic-responsive pharyngitis. He was evaluated
      with multiple psychiatric rating scales for obsessive-compulsive disorder and
      Tourette's syndrome, as well as with serologic assays and radiologic studies.
      RESULTS: In all respects except age our patient fulfilled established criteria
      for PANDAS. Assays for antibodies to group A beta-hematolytic streptococci, serum
      D8,17 lymphocytes, antistriatal (neuronal) antibodies, and anticytoskeletal
      antibodies all supported the hypothesis that a poststreptococcal process was
      active. Magnetic resonance imaging was abnormal and is described. CONCLUSIONS:
      The findings suggest that this patient's illness is similar to PANDAS in
      presentation and that poststreptococcal disease may result in adult-onset
      obsessive-compulsive disorder.

PMID- 11331103
TI  - Quantitative immunocytochemistry of glia in the cerebellar cortex of old ethanol
      fed rats.
AB  - It is clear from results of studies in this laboratory that chronic ethanol
      consumption causes regression of the extensive Purkinje neuron (PN) dendritic
      arbor. There are, however, a paucity of studies on the effects of chronic ethanol
      consumption on glia cells that reside in the molecular layer of the cerebellar
      cortex with PN dendrites. The purpose of the present study was to investigate the
      possibility that chronic ethanol consumption in old F344 rats results in gliosis
      within the molecular layer of the cerebellar cortex. Ten 12-month-old, male, F344
      rats received a liquid diet containing 35% ethanol for 40 weeks. Pair-fed
      controls (n=10) received a liquid diet in which maltose dextrins were substituted
      for ethanol. Chow-fed rats (n=10) served as controls for age. At the end of the
      treatment period, rats were euthanized and perfused through the aorta, and
      cerebella were prepared for immunocytochemistry. Free floating sections were
      stained with (1) glial fibrillary acidic protein antibody for labeling of
      Bergmann glial cells and fibers, (2) OX-42 antibody for labeling of microglia,
      and (3) 0.5% cresyl violet for estimates of molecular layer volume. Results
      indicate that the densities of Bergmann glial cell processes and microglia within
      the cerebellar molecular layer are not altered by ethanol consumption.

PMID- 11331104
TI  - Use of rat models to mimic alterations in iron homeostasis during human alcohol
      abuse and cirrhosis.
AB  - With alcoholism, there are marked disturbances in iron homeostasis that are
      linked to alterations in serum transferrin and ferritin concentrations. This
      study identifies rat models of alcohol abuse that closely mimic these
      disturbances. Male rats were placed in one of the following three protocols: (1)
      pair-feeding of liquid diets for 1-8 weeks; (2) agar-block feeding for 8 weeks;
      or (3) generation of cirrhosis with CCl(4). Serum samples were analyzed for
      ferritin, transferrin, and iron levels, and the transferrin iron saturation and
      ferritin/transferrin ratios were calculated. Liver iron concentrations were also
      determined. Serum transferrin levels were elevated in animals fed alcohol for 8
      weeks in pair-feeding and agar-block feeding protocols, but reduced in rats with
      cirrhosis. Serum ferritin concentration was reduced in rats fed ethanol in the
      liquid diet, but increased in rats consuming ethanol in agar blocks, in rats pair
      fed the liquid control diet, and in rats with cirrhosis. This finding was
      mirrored by liver nonheme iron concentrations in all experimental groups, but not
      in the corresponding control groups. Serum iron levels were significantly
      elevated only in rats fed the liquid control diet. There was a progressive
      decrease in transferrin iron saturation and ferritin/transferrin ratios for
      animals fed ethanol in the liquid diet, but not when ethanol was ingested from
      agar blocks. The development of cirrhosis resulted in elevated liver iron
      concentrations and doubled ferritin/transferrin ratios. It is concluded that
      these models may be used to study disturbances in iron homeostasis that occur
      during alcohol abuse and the (subsequent) development of liver disease.

PMID- 11331105
TI  - Extracellular magnesium regulates nuclear and perinuclear free ionized calcium in
      cerebral vascular smooth muscle cells: possible relation to alcohol and central
      nervous system injury.
AB  - Quantitative digital imaging microscopy, confocal laser scanning microscopy
      (CLSM), and multiple molecular fluorescent probes were utilized to test the
      hypothesis that cerebral vascular muscle cell nuclear ([Ca(2+)](n)), perinuclear
      ([Ca(2+)](pn)), and cytoplasmic free calcium ([Ca(2+)](i)) levels are regulated
      by the concentration of extracellular free magnesium ions ([Mg(2+)](o)). Primary
      cultured canine cerebral vascular smooth muscle cells were loaded with either
      fura-2/AM, indo-1/AM, or fluo-3/AM, and the subcellular Ca(2+) responses to
      stepwise reduction in [Mg(2+)](o) (i.e., from 1.36 to 0.17 mM) were analyzed over
      time. With normal 1.36 mM [Mg(2+)](o)-containing incubation media, basal mean
      [Ca(2+)](i) was 89.6+/-15 nM. Lowering [Mg(2+)](o) to 1.07, 0.88, 0.48, and 0.17
      mM resulted in rapid (<4 min) increments in [Ca(2+)](i) going to 213+/-43, 368+/
      67, 471+/-77, and 642+/-98 nM, respectively; the longer the exposure time (up to
      30 min) to lowered [Mg(2+)](o), the higher the [Ca(2+)](i). Restoration of
      [Mg(2+)](o) to normal caused decreases in [Ca(2+)](i) to 215.9+/-42.3 nM, but
      only complete removal of [Ca(2+)](o) returned [Ca(2+)](i) to basal levels.
      Results show that basal [Ca(2+)](pn) (282+/-92 nM) exceeds basal cytoplasmic
      Ca(2+) (61+/-27.8 nM) and [Ca(2+)](n) (20+/-7.6 nM). However, reduction of normal
      [Mg(2+)](o) to 0.48 mM resulted in dramatic, rapid rises in all subcellular
      compartments, where [Ca(2+)](pn) (1503+/-102 nM)>cytoplasmic Ca(2+) (688+/-49 nM)
      approximately equal to [Ca(2+)](n) (674+/-12 nM). Nuclear Ca(2+) rose
      dramatically (e.g., 35-40 times basal levels). Both verapamil (1 microM) and
      Ni(2+) (5 mM) prevented, completely, the rises in Ca(2+) in all compartments,
      suggesting that Mg(2+)-dependent Ca(2+) accumulation may be dependent on nuclear,
      endoplasmic reticulum-Golgi, and cytoplasmic L-type voltage membrane-regulated
      Ca(2+) channels. The normally low [Ca(2+)](n) suggests that Ca(2+) does not
      transport passively across the nuclear membrane in cerebral vascular smooth
      muscle cells. These results may help to explain much of the impact of
      hypomagnesemic states on cerebral-central nervous system pathobiology, and,
      particularly, alcohol-induced strokes.

PMID- 11331106
TI  - Study of polymorphisms in the CYP2E1 gene in patients with alcoholic
      pancreatitis.
AB  - Cytochrome P450IIEI (CYP2E1) is an ethanol-inducible enzyme. Recently, several
      novel polymorphisms in the CYP2E1 gene have been identified. A polymorphism at
      position -35 [G(-35)T] appears to be of functional significance in transcription
      assays. The aim of this study was to investigate if this and other polymorphisms,
      at position -1019 [C(-1019)T], 4808 [G(4808)A], and 7668 [T(7668)A] of the CYP2E1
      gene are associated with alcoholic pancreatitis. DNA was extracted from
      peripheral blood of 38 patients with alcoholic chronic pancreatitis (CP), 19
      patients with alcoholic acute pancreatitis (AP), 46 alcoholic controls (AC), and
      155 normal controls (NC). The polymorphisms were examined by digestion with the
      corresponding restriction endonucleases following PCR amplification. The results
      have shown that the frequencies of the rare alleles of these polymorphisms were
      not significantly different between the CP, AP, and AC groups and NC. Therefore,
      our study results suggest to us that the polymorphisms investigated in the CYP2E1
      gene are unlikely to be involved in the susceptibility and pathogenesis of
      alcoholic pancreatitis.

PMID- 11331107
TI  - A subtoxic interactive toxicity study of ethanol and chromium in male Wistar
      rats.
AB  - The purpose of this study was to evaluate the interactive toxicity of ethanol
      with potassium dichromate (K2Cr2O7-chromium). Young, male Wistar rats (100-120 g)
      were divided into four groups of five or six animals each and were dosed, through
      water, with 10% ethanol (vol./vol.) or 25 ppm chromium or were dosed with a
      combination of ethanol+chromium at the same concentrations for a period of 22
      weeks ad libitum and were maintained on normal diet. Control animals were
      maintained on a normal diet and water for the same period. The serum succinate
      dehydrogenase and liver total triglyceride levels were significantly reduced in
      the three treated groups. The serum alkaline phosphatase levels were
      significantly reduced in ethanol-treated rats, and there was no significant
      change in the acid phosphatase activity. Serum aspartate and alanine
      aminotransferase levels in the three treated groups were significantly increased.
      The liver glycogen significantly decreased in both the ethanol-treated and the
      chromium-treated rats. There was a significant increase in liver total
      cholesterol levels in chromium-treated rats. Total glutathione levels were
      significantly decreased in the livers of ethanol-treated and ethanol+chromium
      treated rats. To further substantiate these findings, a histological examination
      of the liver and kidneys was undertaken. The livers of alcohol-treated animals
      showed altered hepatic architecture in the centrilobular and periportal areas,
      with increased sinusoidal space (space of Disse), vacuolation, and necrosis of
      hepatocytes. Similar changes were observed in a histological examination of the
      livers of chromium-treated rats, except that the damage to the hepatocytes was
      more confined to the periportal area. Moreover, histological examination of the
      livers of ethanol+chromium-treated rats revealed uniform damage in the
      centrilobular and periportal areas, as was observed in the groups treated either
      with ethanol or chromium. The histological examination of the kidneys in the
      three treated groups revealed significant damage to the renal tubules and
      Bowman's capsule, which showed vacuolation and degeneration of the basement
      membrane. These findings correlate well with the serum enzyme levels found in the
      treated groups. It is evident from this study that chronic ethanol consumption
      sensitizes the liver to the toxic action of agents such as chromium. It leads to
      impairment of the biochemical functions in the liver, and it causes liver and
      kidney damage. Long-term simultaneous exposure to ethanol and chromium may cause
      severe health problems in people who are alcoholics and work in chrome-plating
      and leather-tanning industries.

PMID- 11331108
TI  - Effect of acamprosate and naltrexone, alone or in combination, on ethanol
      consumption.
AB  - Both acamprosate and naltrexone have demonstrated clinical utility in reducing
      relapse to alcohol use in recovering alcoholics. The present experiments examined
      the effects of acamprosate and naltrexone, either alone or in combination, on
      basal ethanol consumption in a limited-access model with the use of outbred
      Wistar rats. Naltrexone, 0.1 mg/kg, significantly reduced ethanol consumption as
      previously reported. Acamprosate, 50 mg/kg, did not significantly reduce ethanol
      consumption when administered alone and provided no evidence of additive or
      synergistic effects when combined with naltrexone. Acamprosate, 200 mg/kg,
      produced a modest reduction in ethanol consumption when administered alone but no
      evidence of additive or synergistic effects when combined with naltrexone. From
      these findings, it is suggested that a combination approach of these drugs may
      not be any more effective than monotherapy.

PMID- 11331109
TI  - Stress as a mediating factor in the association between the DRD2 TaqI
      polymorphism and alcoholism.
AB  - Results of earlier studies have shown that rating of prior stress exposure in
      preadolescent boys influenced the association between DRD2 genotypes and
      alcoholism risk factors, suggesting that variability in stress exposure, either
      in patient or control samples, could readily account for at least part of the
      confusion in DRD2 study outcomes. In order to test the hypothesis that the DRD2
      A1 allele is only associated with alcoholism in subjects with elevated stress
      exposure, we examined the gene-stress interactional model in a sample of males of
      Mayan descent in the Olancho district of Honduras. Ascertainment was based on an
      epidemiologic, observational cross-sectional design, and the study was approved
      by the Institutional Review Board. A total of 309 adult males (age range 18-87
      years) were interviewed by a physician or a public health nurse, blood samples
      were obtained for genetic studies, and participants were administered the short
      version of the Michigan Alcoholism Screening Test (S-MAST) and the Hispanic
      Stress Inventory (HSI). Three explanatory models were evaluated. The first model
      tested the effect of the demographic variables alone as predictors of MAST
      scores, the second tested the effects of stress and DRD2 genotypes separately,
      and the third tested the effect of the interaction between stress and the DRD2
      genotypes. Neither model 1 nor model 2 yielded significant results; neither MAST
      scores nor HSI scores were found to be associated with DRD2 genotypes. However,
      Model 3 was confirmed reflecting a significant (P<.05) interaction between DRD2
      genotype and stress score as a predictor of MAST score. Additionally, this
      difference was found to be largely accounted by the HSI occupational/economic
      stress score, which had a highly significant (P=.003) interaction with DRD2
      genotype as a predictor of MAST score. This stress score was the only one of four
      that showed levels of stress as high as HSI scores in a US population. The MAST
      scores of A2A2 genotype participants were found to be nearly identical in low
      stress and high stress participants, whereas the MAST scores of A1A2 participants
      increased modestly with stress (P=.01) and that of A1A1 participants increased
      markedly with stress (P=.001). These findings support the hypothesis that DRD2
      genotype-phenotype associations depend on the magnitude of stress exposure, and
      they lend support to the view that variability in DRD2 study outcomes may in part
      be explained by this gene-environment interaction.

PMID- 11331110
TI  - Alcohol stimulates motor activity in selectively bred Sardinian alcohol
      preferring (sP), but not in Sardinian alcohol-nonpreferring (sNP), rats.
AB  - The present study was conducted to evaluate the effect of low doses of ethanol on
      motor activity in selectively bred Sardinian alcohol-preferring (sP) and
      Sardinian alcohol-nonpreferring (sNP) rats. Ethanol was acutely administered at
      the doses of 0, 0.25, and 0.5 g/kg (i.p.) immediately before rat exposure to an
      open-field arena for 15 min. The number of square crossings, used as index of
      motor activity, was significantly lower in saline-treated sP than in saline
      treated sNP rats, suggestive of a genetically determined higher emotional state
      in sP than in sNP rats. Ethanol administration resulted in a dose-dependent,
      significant increase in the number of square crossings in sP rats, whereas it was
      completely ineffective in sNP rats. These results suggest to us that a positive
      relationship exists between ethanol preference and ethanol-induced motor
      stimulation in sP/sNP rat lines.

PMID- 11331111
TI  - Preventive counseling during prenatal care: Pregnancy Risk Assessment Monitoring
      System (PRAMS).
AB  - BACKGROUND: Prenatal care provides an opportunity for counseling about behaviors
      and experiences that increase the likelihood of adverse maternal and fetal
      outcomes. OBJECTIVE: To document (1) prevalence of preventive health counseling
      during prenatal care, (2) prevalence of women in higher need of counseling about
      specific health concerns, and (3) whether women in higher need for counseling
      were more likely than women in lower need to have received counseling. METHODS:
      Analysis of the Pregnancy Risk Assessment Monitoring System (PRAMS), a state
      specific, population-based, random sample of postpartum women, was performed by
      using data from 14 states for births during 1997 or 1998, for a total of 24,620
      participants. Outcome measures included report of preventive health counseling
      during prenatal visits by specific topic as well as behaviors and experiences
      about cigarette use, alcohol use, breast-feeding, partner violence, and preterm
      labor. RESULTS: The percentage of women that report preventive counseling during
      prenatal care is relatively high (> or =75%) for 9 of 13 topics. However, the
      percentage of women that report counseling is relatively low (<75%) for partner
      violence, seat belt use, illegal drug use, and human immunodeficiency virus (HIV)
      risk. Except for counseling about cigarette and alcohol use, women in higher
      need, compared with women in lower need, for three other health topics were not
      significantly more likely to receive counseling. CONCLUSIONS: Preventive health
      counseling for partner violence, seat-belt use, illegal drug use, and risk of HIV
      could be increased across prenatal settings. Counseling should involve assessment
      of risks, with focused counseling related to those risks.

PMID- 11331112
TI  - State gun control advocacy tactics and resources.
AB  - CONTEXT: Enacting state laws to regulate firearm use, availability, or
      manufacture is one plausible strategy for preventing firearm-related injuries.
      Organizations that use a wide range of advocacy tactics may be successful in
      promoting gun control policies. OBJECTIVES: To describe tactics commonly used by
      groups that advocate for state gun control laws and to assess whether financial
      resources were associated with groups' use of these advocacy tactics.
      DESIGN/PARTICIPANTS: We identified 679 local and state organizations potentially
      active on state-level gun control issues in 1998 and mailed a 153-item
      questionnaire to the groups' leaders. MAIN OUTCOMES: Organizations' use of 35 gun
      control advocacy tactics. RESULTS: Seventy-nine percent (n=538) of groups
      responded to our survey, and, of those eligible, eighty-one percent (n=207)
      completed questionnaires. Organizations commonly used public education, media,
      and legislative lobbying tactics, and fewer engaged in electioneering and
      litigation. Except for lobbying, no associations were found between groups' use
      of advocacy tactics and their level of financial resources. CONCLUSIONS:
      Organizations advocating for state gun control laws have a varied tactical
      repertoire, with fewer using electioneering and litigation than other approaches.
      Financial resources do not appear to be the determining factor in the advocacy
      methods employed.

PMID- 11331113
TI  - Evaluation of a first aid and home safety program for Hispanic migrant
      adolescents.
AB  - BACKGROUND: Unintentional injuries are the major cause of death among children,
      adolescents, and young adults. This article presents an evaluation of an injury
      prevention program for 11- to 16-year-old, Hispanic migrant youth. DESIGN:
      Randomized controlled trial with two conditions: first aid and home safety
      training and tobacco and alcohol prevention. Participants were assessed at
      baseline, at immediate post-intervention, and at 1-year follow-up. PARTICIPANTS:
      A total of 660 Hispanic adolescent and parent pairs participated in a program
      entitled Sembrando Salud (sowing the seeds of health). INTERVENTION: The
      intervention consisted of two conditions: first aid and home safety training and
      tobacco and alcohol prevention. Both groups were exposed to an eight-session,
      multimedia program presented by bilingual, bicultural college students. The
      sessions consisted of lectures, discussions, and skills development and practice.
      OUTCOME MEASURES: To examine the efficacy of the first aid and home safety
      intervention, adolescents were assessed for changes in first aid confidence,
      knowledge of items in a first aid kit, knowledge of how to respond in an
      emergency situation, acquisition of a first aid kit, and behavioral skills
      testing in response to two emergency scenarios. RESULTS: Similar changes in
      confidence were observed in both groups after the intervention. Participants in
      the first aid and home safety program were better able to identify items to
      include in a first aid kit, how to respond in an emergency situation, and
      reported fewer erroneous victim-caring procedures than the tobacco and alcohol
      prevention group. CONCLUSIONS: Sembrando Salud was successful at achieving and
      maintaining change in confidence and knowledge of first aid and emergency
      response skills over a yearlong period.

PMID- 11331114
TI  - Health department clinics as pediatric immunization providers: a national survey.
AB  - OBJECTIVE: To describe a national sample of health department immunization
      clinics in terms of populations served, patient volume trends, services offered,
      and immunization practices. METHODS: Telephone survey conducted with health
      departments sampled from a national database, using probability proportional to
      population size. RESULTS: All (100%) 166 sampled and eligible clinics completed
      the survey. The majority of pediatric patients were uninsured (42%) or enrolled
      in Medicaid (34%). Most children (69%) and adolescents (70%) were referred to the
      health department, with only 12% using these clinics as a medical home. A number
      of clinics (72%) reported recent increases in adolescents served. Less than 25%
      of clinics offered comprehensive care, 47% conducted semiannual coverage
      assessments, and 76% and 38% operated recall systems for children and
      adolescents. Storage of records in an electronic database was common (83%).
      CONCLUSIONS: Although the majority of these clinics do not provide comprehensive
      care, they continue to serve vulnerable children, including adolescents, Medicaid
      enrollees, and the uninsured, and may represent the main contact with the
      healthcare system for such patients. Because assuring the immunization of these
      children is essential to their health and the health of our nation as a whole,
      this immunization safety net must be preserved. Experience implementing key
      recommendations such as coverage assessment and feedback as well as reminder or
      recall may enable health department staff to assist private provider colleagues.
      Further research is needed to investigate how patient populations, services
      offered, and immunization practices vary by different clinic characteristics.

PMID- 11331115
TI  - Preventing transmission of hepatitis B virus from people with chronic infection.
AB  - BACKGROUND: People with chronic hepatitis B virus (HBV) infection are the major
      source of HBV transmission in the United States. The Public Health Service
      recommends prevention counseling for HBV-infected people and vaccination of their
      household contacts and sexual partners. OBJECTIVES: To describe the
      implementation of these recommendations by community physicians. METHODS:
      Telephone survey of 69 people with chronic HBV infection and their healthcare
      providers, October 1997 through November 1997, in San Diego, California. MAIN
      OUTCOME MEASURES: Counseling of people with chronic HBV infection and vaccination
      of their household contacts and sexual partners. RESULTS: Forty-three percent of
      providers reported providing prevention counseling to their HBV-infected patients
      to reduce transmission; 16% of patients reported receiving counseling. For the 32
      pairs for which both the patient and provider could be reached and the patients
      were aware of their HBV infection, 20 (63%) providers reported counseling
      patients, and 10 (50%) of these providers' patients reported receiving
      counseling. Fifty-five percent of providers recommended vaccination of contacts;
      13% of eligible adult household contacts and sexual partners and 20% of eligible
      child household contacts had begun hepatitis B vaccination. CONCLUSIONS:
      Prevention counseling of people with chronic HBV infection and vaccination of
      their contacts occur infrequently despite guidelines and an effective vaccine.
      Collaborative efforts between providers and people involved in public health are
      needed to improve delivery of these preventive health services.

PMID- 11331116
TI  - Knowledge of partner risk and secondary transmission of HIV.
AB  - BACKGROUND: The number and proportion of people living longer with HIV and the
      proportion of people infected heterosexually have increased. We measured the
      frequency with which people with heterosexually acquired AIDS knew their
      partners' risk behaviors, the extent of secondary heterosexual transmission of
      HIV, and characterized people at risk for secondary heterosexual transmission.
      METHODS: For each of five sites (Alabama, California, Florida, New Jersey, and
      Texas) and for New York City, a sample of adults with AIDS was interviewed.
      Primary heterosexual transmission was contact with a partner who had a known risk
      factor for HIV infection. Secondary transmission was contact with an HIV-positive
      partner not known to have a risk for HIV. RESULTS: Among men, 35% knew that a
      sexual partner was HIV infected, 56% of women knew that a sexual partner was HIV
      infected. Among women, 12% knew that a partner was bisexual. Overall, 79% (460 of
      581) reported a partner with a primary risk for HIV; among men, 236 of 293 (81%),
      and among women, 224 of 288 (78%) reported a partner with a primary risk. People
      categorized with secondary transmission were significantly more likely to be
      black and never married. People categorized with secondary transmission were more
      frequently women (53%), had less than a high school education (48%), and a
      history of drug use (52%). Men categorized with secondary transmission of HIV had
      a mean of 22 heterosexual partners; women had a mean of 16 partners. CONCLUSIONS:
      We found that many heterosexuals with AIDS did not know their sexual partners'
      risk for HIV, and that secondary heterosexual transmission probably results in a
      small proportion of all AIDS cases in the U.S.

PMID- 11331117
TI  - Comparing physical activity questionnaires for youth: seasonal vs annual format.
AB  - BACKGROUND: In large cohort studies of older children, self-report is the only
      practical way to assess physical activity. Assessing usual activity over the
      entire year is desirable, but children and adolescents may overestimate
      activities with high seasonal variability. Use of questionnaires in which
      individuals report each activity by season may improve accuracy. METHODS: A total
      of 6782 girls and 5110 boys, aged 9-14 years in 1996, completed self-administered
      activity questionnaires in 1996 and in 1997. In 1996, participants reported the
      average time spent in each of 17 activities during the previous 12 months; in
      1997, we also asked for the average time spent in the previous year, but within
      each of the four seasons. RESULTS: Girls reported a median of 12.8 hours/week
      total activity in 1996 and 10.4 hours/week in 1997. For boys, the estimates were
      15.5 hours/week and 13.4 hours/week, respectively. Girls and boys within 1-year
      age strata (e.g., comparison of 10-year olds in 1996 with 10-year olds in 1997)
      reported an average of 3.7 and 3.1 fewer hours per week, respectively, on the
      1997 seasonal format versus the 1996 annual format questionnaire. In longitudinal
      analyses, the difference between the annual and the seasonal estimates was
      greater if participants did the activity in fewer seasons in 1997. CONCLUSIONS:
      In comparison to an annual format questionnaire, a seasonal format questionnaire
      may improve accuracy of self-report of physical activity by reducing over
      reporting of activities in which pre-adolescents and adolescents engage in fewer
      seasons.

PMID- 11331118
TI  - Curriculum assessment for prevention topics and the population perspective.
AB  - BACKGROUND: According to the Association of American Medical College's (AAMC)
      Senior Questionnaire, medical students spend an inadequate amount of time
      learning about health promotion, disease prevention, and the population health
      perspective. OBJECTIVE: Determine the health promotion/disease prevention (HPDP)
      content of the medical school curriculum at the University of Kansas School of
      Medicine, using an inventory of knowledge and skills in HPDP and using physician
      education objectives from Healthy People 2000. METHODS: A 121-item survey to
      evaluate curriculum content was developed. All course directors evaluated their
      course by using this instrument. An average of three medical students used this
      instrument to assess each curriculum lecture and every clinical clerkship day in
      the required medical school curriculum. A teaching session was defined as
      spending a minimum of 3-5 minutes teaching an HPDP topic. RESULTS: Of 21 required
      courses in the medical school curriculum, 11 accounted for the 393 teaching
      sessions in HPDP. Seventy-five percent (293 sessions) of these dealt with
      clinical prevention. Quantitative methods received 40 sessions, whereas the
      health services organization and delivery and the community dimensions of medical
      practice received 37 and 23 sessions, respectively. Course directors and students
      disagreed significantly in which HPDP topics were taught in the curriculum.
      CONCLUSIONS: Clinical prevention was fairly well covered in the medical school
      curriculum. Quantitative methods, health services organization and delivery, and
      community dimensions of medical practice were poorly covered. This assessment was
      used to substantially improve the curriculum. To track and improve curriculum
      content in all courses, course directors need to know more precise details about
      the content of their courses, so this detail can be used to better evaluate the
      overall curriculum.

PMID- 11331119
TI  - Performance measures: are we measuring what matters?
AB  - BACKGROUND: The ultimate intent of healthcare performance measures is to improve
      health status by stimulating improvements to healthcare quality. This report
      evaluates how well current performance measurement sets address the leading
      causes of illness and death in the United States, using the Health Plan Employer
      Data and Information Set (HEDIS) as an example. METHODS: We assessed whether
      HEDIS measures exist for the leading causes of illness and death according to
      five commonly used indices: physiologic cause of death, underlying cause of
      death, disability-adjusted life years, healthcare expenditures, and missed work
      days. RESULTS: Fewer than one half of the leading causes of morbidity and
      mortality are addressed by current measures. CONCLUSIONS: The opportunities for
      using accurate and meaningful measurement for disease prevention and health
      promotion are substantial, yet this potential remains only partly realized and
      depends on further expansion of performance measurement efforts.

PMID- 11331120
TI  - Self-reported weight and height: implications for obesity research.
AB  - BACKGROUND: Self-reported weight and height are under- and over-reported,
      respectively, in epidemiologic studies. This tendency, which may adversely affect
      study operations, has not been evaluated among subjects being enrolled into a
      weight-loss program. METHODS: Self-reported weight, height, and body mass index
      (BMI) were compared to measured values in 97 overweight or obese (BMI>27.3) women
      being enrolled into a randomized, controlled trial of two behavioral
      interventions for weight loss. The effects of demographic factors, baseline
      weight, baseline height, and baseline BMI on weight and height reporting were
      assessed. RESULTS: There was a significant difference between measured and
      reported weight (mean difference=-3.75 lb, p=0.0001) and height (mean
      difference=+0.35 in., p=0.0007). The mean difference between measured and
      reported BMI was -1.14 kg/m(2) (p=0.0001). Unemployed, retired, or disabled women
      were more likely to under-report their BMI than employed women (p=0.001). Six
      percent of subjects who were initially considered eligible for the study on the
      basis of the self-report were eventually excluded from the study because they did
      not meet the inclusion criterion for BMI. CONCLUSIONS: Obese women who seek
      weight-loss assistance tend to under-report their weight and over-report their
      height, suggesting that self-reported data are likely to be inaccurate.
      Misreporting is apparently influenced by employment and disability and has the
      potential to complicate recruitment of subjects for research studies.

PMID- 11331121
TI  - The risk of acquiring hepatitis B or C among public safety workers: a systematic
      review.
AB  - CONTEXT: Determination of the occupational risk of hepatitis B and C to public
      safety workers is important in identifying prevention opportunities and has
      significant legal and policy implications. OBJECTIVES: Characterize the risk of
      occupationally acquired infection: (1) risk of exposure to blood and body fluids,
      (2) seroprevalence of hepatitis B and C in the source population, and (3) risk of
      infection after exposure. DATA SOURCES: Electronic search of MEDLINE (1991-1999),
      HealthStar (1982-1999), and CINAHL (1975-1999) supplemented by selected reference
      citations and correspondence with authors of relevant articles. STUDY SELECTION:
      Peer-reviewed journal articles (N=702) that addressed the transmission of
      hepatitis B and C in law enforcement, correctional, fire, emergency medical
      services, and healthcare personnel were identified. One hundred five (15.0%)
      articles were selected for full-text retrieval; 72 (68.6%) were selected for
      inclusion. DATA ABSTRACTION: Articles selected for inclusion were abstracted by
      two reviewers and checked by a third reviewer, using a standard reporting form.
      DATA SYNTHESIS: Evidence tables were constructed, using the standardized
      abstracts. The tables were designed to summarize data for the key elements of the
      risk analysis. CONCLUSIONS: Data suggest that emergency medical service (EMS)
      providers are at increased risk of contracting hepatitis B, but data have failed
      to show an increased prevalence of hepatitis C. EMS providers have exposure risks
      similar to those of hospital-based healthcare workers. Other public safety
      workers appear to have lower rates of exposure. Urban areas have much higher
      prevalence of disease, and public safety workers in those areas are likely to
      experience a higher incidence of exposure events.

PMID- 11331122
TI  - Images in preventive medicine. Bangladesh "information highway" in the year 2000.

PMID- 11331123
TI  - The National Immunization Survey: information for action.

PMID- 11331124
TI  - Measuring the success of the U.S. childhood immunization system.

PMID- 11331125
TI  - Forty years and four surveys: how does our measuring measure up?
AB  - OBJECTIVE: This article reviews four surveys methodologies that have been used
      over the past 40 years to assess immunization rates in young children in the
      United States. These methods include three national surveys: (1) United States
      Immunization Survey (1959-1985), which was first a household and then a telephone
      survey; (2) National Health Interview Survey (1991-present), which interviews
      people in their homes; and (3) National Immunization Survey (1994-present), a
      random-digit-dialing telephone survey. In addition, a series of retrospective
      school record surveys that used standard sampling and assessment methodologies
      were conducted nationally during 4 school years September 1990-May 1991. METHODS:
      Federal publications, National Immunization Conference proceedings, and Centers
      for Disease Control and Prevention (CDC) internal reports regarding national
      immunization surveys were reviewed. The methodology used in each survey is
      presented, and selected examples of previously tabulated results are presented.
      CONCLUSIONS: The assessment of immunization coverage in American preschool
      children requires ongoing commitment and survey expertise. Over the past 40 years
      the CDC's efforts to determine vaccination coverage in young children has evolved
      from the comparatively simple United States Immunization Survey to the current
      National Immunization Survey that utilizes sophisticated statistical and survey
      techniques to obtain the most-accurate results yet available.

PMID- 11331126
TI  - Population-based surveys and their role in public health.

PMID- 11331127
TI  - Overview of the sampling design and statistical methods used in the National
      Immunization Survey.
AB  - Abstract: The National Immunization Survey (NIS) is a large federally funded
      survey designed to estimate vaccination coverage rates for children residing in
      the United States aged 19 to 35 months. In 1999, over 8 million telephone call
      attempts were made to obtain provider-reported vaccination histories on 22,521
      children in the age range of interest.

PMID- 11331128
TI  - Comparison of NIS and NHIS/NIPRCS vaccination coverage estimates. National
      Immunization Survey. National Health Interview Survey/National Immunization
      Provider Record Check Study.
AB  - BACKGROUND: The National Immunization Survey (NIS) and the National Health
      Interview Survey (NHIS) produce national coverage estimates for children aged 19
      months to 35 months. The NIS is a cost-effective, random-digit-dialing telephone
      survey that produces national and state-level vaccination coverage estimates. The
      National Immunization Provider Record Check Study (NIPRCS) is conducted in
      conjunction with the annual NHIS, which is a face-to-face household survey. As
      the NIS is a telephone survey, potential coverage bias exists as the survey
      excludes children living in nontelephone households. METHODS: To assess the
      validity of estimates of vaccine coverage from the NIS, we compared 1995 and 1996
      NIS national estimates with results from the NHIS/NIPRCS for the same years.
      RESULTS: Both the NIS and the NHIS/NIPRCS produce similar results. CONCLUSION:
      The NHIS/NIPRCS supports the findings of the NIS.

PMID- 11331129
TI  - Changes in vaccination coverage estimates among children aged 19-35 months in the
      United States, 1996-1999.
AB  - BACKGROUND: Childhood vaccinations have a major impact on the reduction and
      elimination of many causes of morbidity and mortality among children. Monitoring
      of annual vaccination coverage levels over time is necessary to characterize
      undervaccination. Here, coverage estimates for 1996 (1997 for varicella) were
      compared with those of 1999. METHODS: Immunization coverage among children aged
      19 to 35 months in 1996 (1997 for varicella) and 1999 for a variety of vaccines
      and vaccine series were compared using Wald chi-square tests and data from the
      National Immunization Survey. RESULTS: Record high immunization coverage among
      children aged 19 to 35 months in the United States has increased by a
      statistically significant amount between 1996 and 1999 for diphtheria, tetanus,
      and pertussis; measles, mumps, and rubella; Haemophilus influenzae type b;
      hepatitis B; and standard series made up of these individual vaccines. Coverage
      with the vaccine for varicella dramatically increased between 1997 and 1999.
      However, between 1996 and 1999, coverage with three or more doses of polio
      vaccine decreased by a small but statistically significant amount. CONCLUSION:
      Despite the drop for polio vaccine, coverage remains high. Continued monitoring
      is required to determine if the drop in polio coverage is a cause for concern.

PMID- 11331130
TI  - Vaccination visits in early childhood: just one more visit to be fully
      vaccinated.
AB  - BACKGROUND: This study characterizes the healthcare visits at which children
      receive vaccinations, including the number of these visits and the number of
      vaccinations that are administered. METHODS: The 1999 National Immunization
      Survey (NIS) is a nationally representative sample of children aged 19 to 35
      months, verified by provider records, that is conducted to obtain estimates of
      vaccination coverage rates. We describe the number of healthcare visits in which
      one or more vaccinations were given, the number of vaccinations given at these
      visits, and the number of visits and vaccinations needed for an underimmunized
      child to complete the recommended vaccination series. RESULTS: Of the children
      who did not receive all doses of the recommended vaccinations (4:3:1:3:3
      vaccination series), three fourths had four or more immunization visits.
      Vaccination coverage increased as the number of visits increased, and children
      who had completed the series were more likely to receive multiple vaccinations
      than those who had not. Most children (70.7%) received a maximum of four
      vaccinations in any immunization visit. The majority of children (73.5%) who had
      not completed the 4:3:1:3:3 vaccination series needed only a single visit to
      complete the series. The majority (61.7%) of children who needed only one visit
      also needed only one additional vaccination. CONCLUSIONS: While estimated
      national coverage for all recommended vaccinations is considerably below the
      Healthy People 2000 and Healthy People 2010 goal of 90%, achieving this goal is
      in essence just one visit away. If all children who needed one more visit were to
      receive that final visit, the national coverage among children 19 to 35 months
      for all recommended vaccinations would be 93%.

PMID- 11331131
TI  - U.S. children living in and near poverty: risk of vaccine-preventable diseases.
AB  - BACKGROUND: Poverty and factors associated with poverty are strong and persistent
      barriers to childhood immunization. Substantive differences in coverage with
      basic vaccinations have been consistently observed over time between children
      living in poverty and those who are not. METHODS: The National Immunization
      Survey (NIS) uses a random-digit-dialing sample of telephone numbers in each
      state and in 28 urban areas. The NIS provides vaccination coverage information
      representative of all U.S. children aged 19 to 35 months. We categorized children
      in the NIS using Bureau of Census categories of poverty as follows: "above
      poverty" for household income > or = 125% of the federal poverty threshold for
      the household's size and composition; "near poverty," 100% to <125% of the
      poverty threshold; "intermediate poverty," 50% to <100% of the poverty threshold;
      and "severe poverty," <50% of the poverty threshold. We described coverage with
      basic vaccinations from 1996 through 1999 by poverty category and compare
      coverage between children in poverty and above poverty. RESULTS: From 1996 to
      1999, estimated vaccination coverage with the basic vaccine series was
      consistently higher among children living above the poverty level than all other
      children. The difference in estimated vaccination coverage between children
      living in severe poverty and those living above poverty was 13.6 percentage
      points in 1996, and 10.0 percentage points in 1999. Vaccination coverage with the
      series 4:3:1:3 among children living in near poverty was similar to that of
      children living in poverty (74.7% vs 73.3%, p=0.52). Estimated vaccination
      coverage increased significantly (p<0.05) between 1996 and 1999 for most antigens
      among children living above poverty and among those living in intermediate and
      severe poverty. Vaccination coverage among children living in poverty increased
      significantly (p<0.05) between 1996 and 1999 in 1 of the 28 urban areas in the
      NIS. CONCLUSIONS: Low vaccination coverage among children living in and near
      poverty is a persistent problem in the United States. Additional efforts are
      needed to improve coverage.

PMID- 11331132
TI  - Vaccination status of children in the Women, Infants, and Children (WIC) Program:
      are we doing enough to improve coverage?
AB  - BACKGROUND: Vaccination-promoting strategies in the Supplemental Nutrition
      Program for Women, Infants, and Children (WIC) have been shown to produce
      dramatic improvements in coverage and other health outcomes. OBJECTIVES: To
      determine national and state-specific population-based vaccine coverage rates
      among preschool children who participate in the WIC program, and to describe the
      strategies for promoting vaccination in WIC. DESIGN/METHODS: Demographic data,
      WIC participation, and vaccination histories for children aged 24 to 35 months in
      1999 were collected from parents through the National Immunization Survey. The
      healthcare providers for the children in the survey were contacted to verify and
      complete vaccination information. We defined children as up-to-date (UTD) if they
      had received four doses of diphtheria and tetanus toxoids and pertussis vaccine
      (DPT), three doses of poliovirus vaccine, one dose of measles-mumps-rubella
      vaccine (MMR), and three doses of Haemophilus influenzae type b vaccine (Hib) by
      24 months. Description of state-level vaccination-promoting activities in WIC was
      collected through an annual survey completed by the state WIC and immunization
      program directors. RESULTS: Complete data were collected on 15,766 children, of
      whom 7783 (49%) participated in WIC sometime in their lives. Nationally, children
      who had ever participated in WIC were less well-immunized at 24 months compared
      to children who had not: 72.9% UTD (95% CI, 71.3-74.5) versus 80.8% UTD (95% CI,
      79.5-82.1), respectively. In 42 states, 24-month coverage among WIC participants
      was less than among non-WIC participants, including 13 states where the
      difference was > or = 10%. Vaccination activities linked with WIC were reported
      from 76% of 8287 WIC sites nationwide. States conducting more-frequent
      interventions and reaching a higher proportion of WIC participants had 40% higher
      vaccination coverage levels for the WIC participants in that state (p<0.05).
      CONCLUSIONS: Children served by WIC remain less well-immunized than the nation's
      more-affluent children who do not participate in WIC. Thus, WIC remains a good
      place to target these children. This study provides evidence that fully
      implemented WIC linkage works to improve vaccination rates. Strategies that have
      been shown to improve the vaccination coverage levels of WIC participants should
      be expanded and adequately funded to protect these children.

PMID- 11331133
TI  - Vaccination status of children living in rural areas in the United States: are
      they protected?
AB  - OBJECTIVE: To estimate the vaccination coverage levels of children living in
      rural areas and identify statistically significant differences in coverage
      between children living in rural areas and their suburban and urban counterparts.
      METHODS: Children aged 19 to 35 months participating in the 1999 National
      Immunization Survey (NIS) were included in the study. Children were classified as
      living in a rural, urban, or suburban area based on their telephone exchange
      (area code plus the first three digits of the telephone number). Statistically
      significant differences in vaccination coverage levels between the rural
      population and their urban counterparts were determined for individual vaccines
      and vaccine series. RESULTS: Overall, 18% of the children included in the 1999
      NIS lived in a rural area, 46% lived in a suburban area, and 36% lived in an
      urban area. The characteristics of the rural population were: 72% were white, non
      Hispanic; 24% were below the poverty level; 16% had a mother with <12 years of
      education; and 30% received vaccinations from a public provider. Eighty percent
      of rural children, 79% of suburban children, and 77% of urban children completed
      the 4:3:1:3 series. The rural population had statistically significantly lower
      (p<0.01) varicella coverage levels than their suburban and urban counterparts.
      CONCLUSION: Results of this study suggest that children living in rural areas are
      just as likely to receive the basic 4:3:1:3 vaccination series as their suburban
      and urban counterparts. Uptake of the varicella vaccine appears to be slower in
      rural areas than urban areas. Further studies are recommended to identify the
      risk factors for not receiving the varicella vaccine in rural areas.

PMID- 11331134
TI  - Undervaccinated African-American preschoolers: a case of missed opportunities.
AB  - OBJECTIVE: To identify factors associated with undervaccination of African
      American preschoolers, to describe the number of vaccination visits made by
      undervaccinated children and the number of visits needed to be series complete,
      and to describe the children who did not receive the single dose of measles
      containing vaccine recommended for preschoolers. METHODS: We used the 1999
      National Immunization Survey (NIS) to describe vaccination coverage for the
      4:3:1:3 vaccine series (four doses of diphtheria and tetanus toxoids and
      pertussis vaccine, three doses of poliovirus vaccine, one dose of any measles
      containing vaccine, and three doses of Haemophilus influenzae type b vaccine)
      among non-Hispanic, African-American preschoolers due to concerns that they may
      be at risk of undervaccination. Children who did not complete this basic vaccine
      series were classified for further analysis according to the number of doses they
      lacked (i.e., one dose missed, two or three doses missed, or four or more doses
      missed). Significant associations between demographic characteristics and
      vaccination status or degree of undervaccination were determined. RESULTS: Of the
      26.2% of African-American preschoolers who did not complete the 4:3:1:3 vaccine
      series, 40.3% lacked one, 35.3% lacked two or three, and 25.0% lacked four or
      more doses of vaccine. Children who did not complete the 4:3:1:3 vaccine series
      were less likely to have married mothers, were less likely to have mothers aged >
      or = 35 years, or were less likely to be up to date at age 3 months than the
      children who completed the 4:3:1:3 vaccine series. Among the undervaccinated,
      63.7% had a sufficient number of vaccination visits to have completed the basic
      series. However, most (78.7%) of the severely undervaccinated (children who
      lacked more than three doses of vaccine) had three or fewer vaccination visits.
      For 72.6% of the undervaccinated preschoolers, only one additional vaccination
      visit was needed to complete the 4:3:1:3 vaccine series; among these, 78.3% had
      an adequate number of vaccination visits to have completed the series. Overall,
      9.9% of the African-American children aged 19 to 35 months (i.e., approximately
      85,000 African-American children aged 19 to 35 months) were at risk for measles.
      Among the children who lacked more than three doses of vaccine, 68.1% were at
      risk. CONCLUSIONS: Our study suggests that the estimated coverage of 73.8% for
      the 4:3:1:3 vaccine series among African-American children aged 19 to 35 months
      was not a result of limited access to care. On the contrary, 90.5% of African
      American children had enough vaccination visits to complete the series. To raise
      coverage and prevent potential outbreaks, providers should assess each child's
      vaccination status at every visit, and administer all needed vaccinations at that
      time. For the most severely undervaccinated children, this strategy may not be
      adequate, because they did not have the minimum number of vaccination visits
      required for series completion. For these children, other strategies are needed
      for increasing vaccination coverage.

PMID- 11331135
TI  - Variation in vaccination coverage among children of Hispanic ancestry.
AB  - BACKGROUND: Estimated vaccination coverage of Hispanic children is consistently
      lower than that of white non-Hispanic children. "Hispanic ethnicity" defines a
      highly heterogeneous group of the U.S. population; however, vaccination coverage
      by ancestry group has not been studied. This study explores differences in
      vaccination coverage among Hispanic children by ancestry group. METHODS: The
      National Immunization Survey (NIS) uses a random-digit-dial sample of telephone
      numbers in each state and in 28 urban areas. The NIS provides vaccination
      coverage information representative of all U.S. children aged 19 to 35 months. We
      pooled NIS data from 1996 through 1999 and selected Hispanic and white non
      Hispanic children for analysis. We categorized Hispanic children into the
      following ancestry groups: Mexican, Central American, Puerto Rican, Cuban, South
      American, and Dominican. We used t tests to detect differences in coverage
      between children of Hispanic ancestry, by group, compared to white non-Hispanic
      children, by vaccine, and the vaccination series 4:3:1:3. RESULTS: Estimated
      vaccination coverage with 4:3:1:3 was 80.1% (95% CI, 79.6-80.6) among white non
      Hispanic children. Estimated coverage was lower among Puerto Rican (75.8%; 95%
      CI, 72.1-79.5), Cuban (73.1%; 95% CI, 65.1-81.1), Mexican (71.7%; 95% CI, 69.9
      73.5), and Central American (68.7%; 95% CI, 62.0-75.4) children, and was higher
      among South American (82.0%; 95% CI, 75.5-88.5) and Dominican (82.2%; 95% CI,
      75.5-88.5) children; however, these differences were only statistically
      significant for Puerto Rican, Mexican, and Central American children. Among
      children living in poverty, estimated coverage with 4:3:1:3 was lower among
      Mexican (68.0%; 95% CI, 65.1-70.9), Central American (69.7%; 95% CI, 59.8-79.6),
      and South American (69.0%; 95% CI, 50.9-87.1) children than among white non
      Hispanic children (73.4%; 95% CI, 71.6-75.2); however, this difference was
      significant only among Mexican children. Coverage was similar or somewhat higher
      among Puerto Rican (72.9%; 95% CI, 65.7-80.1) and Dominican (80.2%; 95% CI, 68.5
      91.9) children than white non-Hispanic children living below poverty.
      CONCLUSIONS: Findings from the NIS strongly suggest that estimated vaccination
      coverage among children of Hispanic ancestry varies by group. Improved monitoring
      of vaccination coverage among Hispanics by community is necessary, and where
      undervaccination is identified, interventions should be matched to community
      needs.

PMID- 11331136
TI  - Undervaccination with hepatitis B vaccine: missed opportunities or choice?
AB  - BACKGROUND: An estimated 1 million to 1.25 million people in the United States
      are chronically infected with hepatitis B virus (HBV) and are at substantially
      increased risk of developing chronic liver disease, including cirrhosis and
      primary hepatocellular carcinoma. Immunization with hepatitis B vaccine (HepB) is
      the most effective means of preventing HBV infection and its consequences.
      METHODS: To identify and describe children who had not completed the three-dose
      HepB series, we analyzed data from the 1999 National Immunization Survey (NIS).
      Among the 2648 children aged 19 to 35 months who did not complete the HepB
      series, we examined the relationship between the number of doses of HepB received
      and the number of vaccination visits made, receipt of the birth dose of HepB, age
      at the time of first vaccination visit (excluding that for the birth dose of
      HepB), and completion of the 4:3:1:3 series (four doses of diphtheria and tetanus
      toxoids and pertussis vaccine, three doses of poliovirus vaccine, one dose of
      measles-containing vaccine, and three doses of Haemophilus influenzae type b
      vaccine [Hib]). RESULTS: Overall, 11.8% of the children who were included in the
      1999 NIS did not complete the HepB series. Among these series-incomplete
      children, most (79.8%; 95% CI, 77.4%-82.2%) did not receive the birth dose of
      HepB, and most (80.2%; 95% CI, 77.6%-82.8%) had three or more vaccination visits.
      Most of the series-incomplete children (87.3%; 95% CI, 85.1%-89.5%) who had three
      or more vaccination visits received one or two doses of HepB. Among series
      incomplete children with at least three vaccination visits, those who did not
      receive any HepB were more likely to have completed the 4:3:1:3 series (67.1%;
      95% CI, 58.8%-75.4%) than those who received at least one dose of HepB (52.7%;
      95% CI, 49.0%-56.4%). CONCLUSIONS: Children who did not complete the HepB series
      fell into three distinct groups: children who made at least three vaccination
      visits but did not begin the HepB series (n=326); children who made three or more
      vaccination visits and received one or two doses of HepB (n=1835); and children
      who made fewer than three vaccination visits (n=487). Different intervention
      strategies are needed to have an impact on each of these groups, including
      understanding why parents and providers may not be receptive to HepB, decreasing
      missed opportunities to administer HepB, and implementing tracking systems such
      as registries to identify and contact children who are due or overdue for
      vaccinations.

PMID- 11331137
TI  - The future of the National Immunization Survey.

PMID- 11331138
TI  - What's in a number? The use and abuse of survey data.

PMID- 11331139
TI  - Enhancing informed consent for research and treatment.
AB  - Increased scrutiny of informed consent calls for further research into decision
      making by patients who may be at risk for impairments. We review interventions
      designed to improve patient understanding of informed consent. A number of
      studies, within as well as outside psychiatry, have evaluated the effectiveness
      of specific interventions, as well as possible "predictors" of understanding of
      consent, such as subject characteristics, psychiatric symptoms, and cognitive
      impairment. Deficits in patients' understanding of informed consent may be
      partially related to poorly conceived, written, or organized informed consent
      materials; these deficits may be remediable with educational interventions. We
      find that effective interventions include corrected feedback, multiple learning
      trials, and more organized or simplified consent forms. Educational levels of
      patients generally correlate with levels of understanding. Even among individuals
      with psychiatric illness or cognitive impairment, deficits in understanding can
      be remedied with certain educational interventions. A variety of interventions
      can enhance understanding of informed consent.

PMID- 11331140
TI  - Transcranial magnetic stimulation and antidepressive drugs share similar cellular
      effects in rat hippocampus.
AB  - Transcranial magnetic stimulation (TMS) has been proposed as a safe and efficient
      treatment of human clinical depression. Although its antidepressive mechanism of
      action remained unknown, our previous studies indicate that TMS has a long
      lasting effect on neuronal excitability in the hippocampus. We now compare the
      effects of chronic TMS with those of the antidepressant drugs desipramine and
      mianserin. The three treatments did not affect basal conduction in the perforant
      path to the dentate gyrus, but markedly suppressed paired-pulse and frequency
      dependent inhibition, resulting from a reduction in local circuit inhibition in
      the dentate gyrus. Concomitantly, these treatments enhanced the expression of
      long-term potentiation in the perforant path synapse in the dentate gyrus.
      Finally, chronic TMS as well as mianserin suppressed the serotonin-dependent,
      potentiating action of fenfluramine on population spike in the dentate gyrus.
      Thus, TMS, mianserin, and desipramine are likely to affect the same neuronal
      populations, which may be relevant to their antidepressant action.

PMID- 11331141
TI  - Noradrenergic function and clinical outcome in antidepressant pharmacotherapy.
AB  - Controversy remains regarding the role of noradrenergic systems in determining
      clinical response to antidepressant pharmacotherapy. Pineal gland production of
      melatonin can serve as a physiologic index of noradrenergic function. The aim of
      this study was to examine the effects of antidepressant treatment on 24-hour
      urinary excretion of the principle metabolite of melatonin, 6-sulfatoxymelatonin
      in treatment responders and nonresponders. Twenty-four outpatients meeting DSM
      III-R criteria for Major Depression received treatment with either fluvoxamine or
      imipramine for 6 weeks while participating in a placebo-controlled double-blind
      clinical trial. Twenty-four hour excretion of 6-sulfatoxymelatonin was measured
      at baseline and at the conclusion of the treatment trial. Changes in urinary
      excretion of 6-sulfatoxymelatonin distinguished antidepressant responders from
      nonresponders, with a significant increase observed in the former group and a
      significant decrease in the latter. The degree of clinical response was
      correlated with the change in 6-sulfatoxymelatonin excretion. These results
      suggest that enhanced noradrenergic function may play an important role in
      determining clinical response to antidepressant pharmacotherapy.

PMID- 11331142
TI  - Effects of sodium valproate on corticotropin-releasing factor systems in rat
      brain.
AB  - We hypothesized that divalproex sodium, an anticonvulsant effective in the acute
      treatment of mania, may act upon neuropeptide systems that utilize corticotropin
      releasing factor (CRF). Pharmacokinetic studies demonstrated that valproate has
      an apparent elimination half life of 17 minutes in rats after acute
      administration and that there is a nonlinear relationship between chronic dose
      and serum drug concentration. Acute valproate treatment neither altered plasma
      adrenocorticotropic hormone (ACTH) or corticosterone concentrations nor produced
      changes in CRF concentration in any of 10 brain regions examined. Subchronic
      treatment via SC-implanted osmotic minipumps (875 mg/kg/day x 7 days) resulted in
      decreased CRF concentrations in the median eminence and raphe nuclei. Moreover,
      CRF mRNA expression was decreased in the central nucleus of the amygdala (CeA)
      and paraventricular nucleus (PVN) of the hypothalamus. The benzodiazepine
      alprazolam, also a positive modulator of GABAergic function, similarly decreases
      CRF mRNA expression in the CeA. These results suggest that the mood stabilizing
      effects of valproic acid may be mediated in part by alterations in CRF neuronal
      activity.

PMID- 11331143
TI  - Paradoxical hormonal and behavioral responses to hypothyroid and hyperthyroid
      states in the Wistar-Kyoto rat.
AB  - Wistar-Kyoto (WKY) rats show endogenous depressive behavior that can be reversed
      by antidepressants. Given that WKYs exhibit decreased sensitivity to some
      antidepressants and treatment-resistant depressed patients often show
      hypothalamic-pituitary-thyroid (HPT) dysregulation, we examined the behavioral
      and HPT hormonal responses of WKYs to altered thyroid status. "Euthyroid" WKYs
      had elevated basal plasma TSH and T(3) levels as compared to Wistars.
      Hypothyroidism increased TSH levels more in WKYs than in Wistars and increased
      response latency in the open field test (OFT) of WKYs only. Administration of
      T(4) and T(3) suppressed plasma TSH equally in both strains. Wistars responded to
      increased T(3) levels with decreased response latency and increased activity in
      the OFT, but increased immobility in the forced swim test. In contrast, WKYs
      responded only to the high T(3) levels with decreased response latency in the
      OFT. These results suggest the existence of a decreased central nervous system
      sensitivity to thyroid hormones in WKYs that could be related to their depressive
      behavior.

PMID- 11331144
TI  - Molecular cloning of a novel isoform of diphosphoinositol polyphosphate
      phosphohydrolase: a potential target of lithium therapy.
AB  - The mechanisms underlying the therapeutic effects of lithium are largely unknown
      but may involve progressive adaptive alterations at the level of gene expression.
      Using differential display PCR, we identify a novel cDNA fragment, the expression
      of which was increased in the rat frontal cortex after 5 weeks of lithium
      administration. A full-length cDNA (2954-nt) was cloned by arrayed cDNA library
      screening, and sequencing of the clone revealed an open reading frame of 537-bp
      encoding a 179-residue protein. Amino acid sequence comparisons revealed that our
      clone is a member of the Nudix hydrolase family, with the highest percentage of
      homology (95%) being with a subtype of human diphosphoinositol polyphosphate
      phosphohydrolase, hDIPP2. Northern blot analysis revealed that chronic lithium
      treatment significantly increased rDIPP2 mRNA levels in frontal cortex, but not
      in hippocampus, midbrain, and cerebellum. The effect of lithium on rDIPP2 mRNA
      expression was not shared by two other anticonvulsant mood stabilizers,
      carbamazepine and valproate. Time-course studies showed that 1-week of lithium
      had no effect on rDIPP2 mRNA abundance in the frontal cortex. Our results suggest
      that DIPP2 may represent a biologically relevant target of lithium therapy,
      further supporting the notion that abnormalities in inositol phosphate metabolism
      may be significant in the pathophysiology and pharmacotherapy of bipolar
      disorder.

PMID- 11331145
TI  - Chronic effects of triiodothyronine in combination with imipramine on 5-HT
      transporter, 5-HT(1A) and 5-HT(2A) receptors in adult rat brain.
AB  - Triiodothyronine (T3) has been shown to accelerate and potentiate the clinical
      response to tricyclic antidepressant (TCA) treatment in depressive disorders. The
      neurobiological mechanisms underlying these therapeutic effects of T3 are still
      unknown. Since brain serotonin (5-HT) changes have been implicated in the mode of
      action of TCA drugs, the effects of a chronic (7 or 21 days) administration of
      imipramine (10 mg/kg/day) and of a low dose of T3 (4 microg/kg/day), given alone
      or in combination, were investigated on the density of midbrain 5-HT transporters
      and of hippocampal 5-HT(1A) and cortical 5-HT(2A) receptors in adult Wistar rats.
      Neither single nor combined administration of imipramine and T3 for 7 days
      modified the density of 5-HT transporters and of 5-HT(1A) receptors. On day 21,
      the combination did not change imipramine- or T3-induced decrease in 5-HT
      transporter density whereas it prevented imipramine-induced increase in 5-HT(1A)
      receptor density. Whatever the treatment duration, imipramine-T3 combination
      potentiated imipramine-induced decrease in 5-HT(2A) receptor density. On both day
      7 and day 21, T3 given alone had no effects on the density of 5-HT(1A) and 5
      HT(2A) receptors. These data indicate that T3 is able to modulate the long-term
      adaptive changes which occur at the postsynaptic level of 5-HT neurotransmission
      after antidepressant treatment.

PMID- 11331146
TI  - Startle and sensorimotor gating in rats lacking CCK-A receptors.
AB  - Otsuka Long Evans Tokushima Fatty (OLETF) rats lack CCK-A receptors because of a
      genetic mutation. Previous studies have shown that CCK-A receptors seem to play a
      role in the regulation of prepulse inhibition (PPI) of the startle reflex, an
      operational measure of sensorimotor gating. This study investigated baseline and
      drug-disrupted PPI in OLETF rats and their non-mutant counterparts, Long Evans
      Tokushima Otsuka (LETO) rats. Baseline PPI did not differ significantly between
      the two rat genotypes but OLETF rats exhibited a higher acoustic startle response
      compared to LETO rats. Amphetamine (2 mg/kg), and the non-competitive NMDA
      antagonist, dizocilpine (0.1 mg/kg), disrupted PPI in LETO rats but not in the
      OLETF rats. Apomorphine (0.5 mg/kg) failed to disrupt PPI in both LETO and OLETF
      rats, and haloperidol (0.5 mg/kg) produced a comparable facilitation of PPI in
      both groups. In a separate study, OLETF rats were found to be less sensitive to
      the locomotor stimulating effects of amphetamine. These results suggest that CCK
      A receptors play a significant role in the behavioral effects of amphetamine and
      dizocilpine. The PPI response of OLETF rats to amphetamine and dizocilpine is
      similar to normal rats pretreated with atypical antipsychotics, suggesting that
      CCK-A receptors may play an important role in the restoration of drug-disrupted
      PPI by antipsychotics.

PMID- 11331147
TI  - Reversal of diminished inhibitory sensory gating in cocaine addicts by a
      nicotinic cholinergic mechanism.
AB  - Cocaine addiction, as with other stimulant abuse, produces psychotic symptoms.
      Although often moderate to mild in severity, these symptoms are, nevertheless,
      associated with poorer over-all outcome. Recent studies suggest diminished
      nicotinic cholinergic neurotransmission as a mechanism of a physiological deficit
      found in schizophrenia, failure of auditory sensory inhibition. Diminished
      inhibitory sensory gating also occurs in cocaine addicts, probably because of
      their increased catecholaminergic neurotransmission, which blocks the inhibition.
      In the present study, 11 cocaine addicts in the first week of detoxification were
      recorded electrophysiologically, after which the effects of 6 mg of nicotine gum,
      were assessed in a double-blind placebo-controlled crossover design. The test was
      repeated 10 days later. Treatment with nicotine, but not placebo, briefly
      reversed the inhibitory abnormality on both test days. Although nicotine itself
      may not be a desirable therapeutic agent, because desensitization of nicotinic
      receptors limits the time course of its effect, the study identifies a previously
      unexploited therapeutic target for new drug development for the neuropsychiatric
      sequelae of cocaine addiction.

PMID- 11331148
TI  - The ability of environmental context to facilitate psychomotor sensitization to
      amphetamine can be dissociated from its effect on acute drug responsiveness and
      on conditioned responding.
AB  - Doses of amphetamine or cocaine that fail to induce psychomotor sensitization
      when given to a rat in its home cage can produce robust sensitization if given
      immediately following placement into a relatively novel, distinct environment. A
      drug-associated context can serve as a conditioned stimulus, and therefore may
      promote robust sensitization by facilitating associative learning processes. We
      examined this hypothesis by habituating rats to the test environment for 1 or 6-
      8 hr prior to each drug injection, which degrades the ability of environmental
      context to serve as an effective conditioned stimulus. When 0.5 mg/kg of
      amphetamine was administered intravenously immediately after placement into a
      distinct environment there was a large acute psychomotor response (rotational
      behavior) on the first test day, and robust sensitization developed with repeated
      daily injections. When the same treatment was administered in the home cage,
      there was a small acute response and no sensitization developed. The enhanced
      acute response seen in the distinct environment was significantly attenuated by 1
      hr of habituation to the test environment, and completely abolished by 6--8 hr of
      habituation. Also, as little as 1 hr of habituation completely prevented the
      development of a conditioned rotational response. In contrast, neither 1 nor 6--8
      hr of habituation had any effect on the ability of amphetamine to induce robust
      behavioral sensitization. It is concluded that the ability of a distinct
      environment to facilitate sensitization to amphetamine can be dissociated from
      its effect on acute drug responsiveness and from the ability of drug-associated
      environmental stimuli to elicit a conditioned response. Possible mechanisms by
      which a distinct environment facilitates sensitization are discussed.

PMID- 11331149
TI  - Neurofunctional effects of developmental alcohol exposure in alcohol-preferring
      and alcohol-nonpreferring rats.
AB  - The neurofunctional effects of developmental alcohol exposure (3% v/v solution
      from day 15 of gestation to day 7 after parturition) have been investigated in
      Sardinian alcohol-preferring (sP) and alcohol-nonpreferring (sNP) rat lines,
      selectively bred for opposite alcohol preference and consumption. Alcohol
      exposure significantly decreased the rate of ultrasonic emission in sP male pups;
      whereas, it did not affect this indicator of emotional reactivity in sNP animals.
      Perinatal alcohol intake did not influence either learning of an active avoidance
      task or hippocampal long-term potentiation in both offspring lines. Significant
      differences in time spent exploring novel objects were observed between control
      sP and sNP rats subjected to the novel exploration object test. Alcohol exposed
      sP rats, but not alcohol exposed sNP rats, apparently lost the capacity to
      discriminate between the novel and the familiar object, even though this
      difference is difficult to interpret because of the large differences in the
      respective responses to the novel objects. Neurochemical experiments have shown
      that basal levels of dopamine (DA) and homovanillic acid (HVA) were significantly
      higher in the nucleus accumbens (NAC) of sP rats with respect to sNP animals.
      Perinatal alcohol did not affect basal DA and HVA concentrations or amphetamine
      induced DA increase and HVA decrease in the NAC of either sP or sNP offspring.
      These results suggest that subtle behavioral alterations induced by developmental
      exposure to low doses of alcohol, which do not cause malformations and/or overt
      neurotoxicity, may be associated with genetic factors, although not necessarily
      those responsible for differences in alcohol preference.

PMID- 11331151
TI  - Imaging and clinical spectrum of rhabdomyosarcoma in children.
AB  - We retrospectively analyzed the MRI findings of rhabdomyosarcoma (RMSA) in 23
      patients to evaluate its role in staging and management. Heterogeneous signal
      abnormalities were noted in the sarcoma lesions with significant contrast
      enhancement. Seven head and neck cases showed direct bone invasion and
      destruction; only one had distant bony metastasis. Metastasis was noted in the
      lymph nodes, lung, bone, abdominoperitoneum, and head and neck soft tissue. MRI
      findings of RMSA are most helpful in staging and assessing therapeutic response.

PMID- 11331150
TI  - Could reduced cerebrospinal fluid (csf) galanin contribute to restricted eating
      in anorexia nervosa?
AB  - Galanin (GAL) and gamma amino butyric acid (GABA) are orexigenic neuropeptides
      that could contribute to the pathogenesis of anorexia nervosa (AN). To avoid the
      confounding effects of the ill state, we studied women who were recovered (> 1
      year, normal weight, and regular menstrual cycles, no binging or purging) from AN
      (REC AN) and matched healthy control women (NC). CSF GAL was reduced in REC AN
      (64.4 +/- 8.6 pg/ml) compared to NC (72.0 +/- 11.6 pg/ml; p <.05), GABA was
      similar between groups. In the brain, GAL stimulates appetite and fat
      consumption. These data raise the question of whether alterations in brain GAL
      activity plays a role in clinical symptoms in AN, such as food restriction and
      fat avoidance.

PMID- 11331152
TI  - Usefulness of T1-weighted image with fast inversion recovery technique in
      intracranial lesions: comparison with T1-weighted spin echo image.
AB  - To evaluate the usefulness of T1-weighted images using the fast inversion
      recovery (T1FIR) technique as compared with routine T1-weighted spin echo (T1SE)
      images in various intracranial lesions. Routine spin echo and T1FIR images were
      performed in 15 consecutive patients with 18 lesions, cerebral infarction in
      five, astrocytoma in four, vascular lesion in three, encephalomalacia and
      hemorrhage in each two, arachnoid cyst and meningioma in each one. T1FIR images
      were performed with 1.5-T Signa [repetition time (TR)/echo time (TE)/inversion
      time (TI) was 2000/34/800 in 14, 4000/34/1200 in four lesions] and qualitatively
      compared with the T1SE images in signal intensity, lesion detectability,
      determination of lesion extent and conspicuity, contrast between lesion and
      background. Additionally, gray-to-white matter and cerebrospinal fluid (CSF)-to
      white matter contrast were evaluated. The signal intensity of the lesions was
      similar on both T1FIR and T1SE images in all cases. The lesion detectability was
      similar on both sequences in 15 lesions, and the determination of the lesion
      extent was definitely higher in 16 lesions on the T1FIR images. Lesion
      conspicuity was superior in 11, similar in 5, and inferior in 2 patients on the
      T1FIR images. And also, contrast of lesion-to-background, gray-to-white matter,
      and CSF-to-white matter was superior on the T1FIR images. The T1FIR technique
      improved the determination of lesion extent and lesion conspicuity and was
      qualitatively superior for image contrast as compared with T1SE, but it takes
      more time than T1SE. The clinical application of T1FIR images depends on whether
      the superior aspect of the T1FIR images outweighs the disadvantage of the longer
      time required for this technique.

PMID- 11331153
TI  - Spontaneous spinal cerebrospinal fluid leak and intracranial hypotension.
AB  - A case of intracranial hypotension with spontaneous cerebrospinal fluid (CSF)
      leak was reported. A Tc-99m diethyltriaminepentacetic acid radionuclide
      cisternography (RNC) showed the accumulation of radioactivity in the area of the
      subarachnoid space, the poor migration of the isotope over the convexities, and
      the early appearance of kidney and bladder activity. To localize the site of CSF
      leak, RNC will be the choice, and when the time comes, RNC will work well in the
      location of the leak.

PMID- 11331154
TI  - An unusual case of brucellar spondylitis involving both the cervical and lumbar
      spine.
AB  - We report an unusual case of brucellar spondylitis, involving both the cervical
      and lumbar spine. Diagnosis was established using magnetic resonance imaging
      (MRI). An initial plain radiograph of the lumbar spine, showing mild degenerative
      lesions, was misleading. Therefore, institution of a proper treatment was
      delayed.

PMID- 11331155
TI  - Dynamic CT features of mediastinal hemangioma: more information for evaluation.
AB  - Dynamic enhancing feature in mediastinal hemangioma was rarely reported. Slow,
      gradually increasing and prolonged contrast stains are the diagnostic hints in
      our case that avoid the hemorrhagic catastrophe from transthoracic core needle
      biopsy. A rare finding of an aberrant vessel entering into the tumor was valuable
      for operative planning. Dynamic computed tomography (CT) can provide more
      information for evaluation in such cases.

PMID- 11331156
TI  - Mycotic pseudoaneurysm of the aortic arch: an unusual complication of invasive
      pulmonary aspergillosis.
AB  - Invasive pulmonary aspergillosis (IPA) is usually a condition of the
      immunocompromised patients. The organism has a tendency to invade pulmonary blood
      vessels. Extension of a pulmonary parenchymal lesion to involve the mediastinal
      great vessels is very rare. This is the first case where the extension of IPA to
      the aortic arch and the formation of a pseudoaneurysm were demonstrated on serial
      CT scans.

PMID- 11331157
TI  - US and CT findings of tuberculosis of the thyroid: three case reports.
AB  - With two ultrasonographic and two CT films of three cases of thyroid
      tuberculosis, we evaluate the ultrasonographic and CT findings and correlate them
      with the pathologic findings. They are demonstrated as heterogeneous hypoechoic
      mass on ultrasonogram and peripheral-enhancing low-density abscess on CT scan
      with regional lymphadenopathy. Ultrasonography (US) and CT can help the diagnosis
      of thyroid tuberculosis.

PMID- 11331158
TI  - CT features of acute phlegmonous gastritis.
AB  - One case of phlegmonous gastritis is presented. Radiological diagnosis of this
      condition is difficult. In the setting of a clinical suspicion of this condition,
      computed tomography (CT) is the imaging modality of choice.

PMID- 11331159
TI  - Caroli's disease diagnosed in a child by MRCP.
AB  - We describe a case of Caroli's disease associated with a choledochal cyst and
      autosomal recessive polycystic kidney disease in a child whose diagnosis was
      confirmed with magnetic resonance cholangiopancreatography (MRCP), after initial
      abnormalities were seen by ultrasonography. Invasive procedures such as liver
      biopsy or endoscopic retrograde cholangiopancreatography (ERCP) were, therefore,
      not necessary. Recent radiological advances in the diagnosis of Caroli's disease
      with particular emphasis on MRCP are discussed.

PMID- 11331160
TI  - Diffuse perfusion abnormality of the liver parenchyma on angiography-assisted
      helical CT in relation to cirrhosis and previous treatments: a potential
      diagnostic pitfall for detecting hepatocellular carcinoma.
AB  - We evaluated diffuse perfusion abnormality of the liver parenchyma in relation to
      cirrhosis and previous treatments and estimated its potential limitation in
      detecting hepatocellular carcinomas (HCCs) on CT arterial portography (CTAP) and
      CT hepatic arteriography (CTHA). Sixty-one patients of liver cirrhosis with or
      without HCC received both CTAP and CTHA. Irregular defects of enhancement of the
      liver parenchyma on CTAP were noted in 37 of 61 patients (60.7%) and compensatory
      arterial perfusion in these defects on CTHA was noted in 30 of 37 patients
      (81.1%). Most patients had segmental or mixed patterns of enhancement. In
      patients with severe cirrhosis, irregular enhancement was often noted. The
      irregularity was also more often in patients who had had previous treatments.
      Four of 40 HCC nodules in 18 patients with severe irregular perfusion were not
      detected on CTAP and CTHA. Diffuse perfusion abnormalities of the liver
      parenchyma on CTAP and CTHA would decrease the accuracy of tumor detection in HCC
      patients.

PMID- 11331161
TI  - MRI of the wrist.
AB  - In the past, the diagnostic imaging algorithm for evaluating the painful wrist
      included initial plain radiographic examination followed by arthrography,
      tomography, bone scintigraphy, or computed tomography. In recent years, magnetic
      resonance imaging (MRI) has been proven efficacious for diagnosing a number of
      maladies of the bones, ligaments, and soft tissues. MRI can be of aid in
      evaluation of carpal instability, disorders of the triangular fibrocartilage,
      ulnar impaction syndrome, distal radioulnar joint (DRUJ) instability, fracture,
      avascular necrosis (AVN), tendinopathy, nerve entrapment syndromes, synovial
      abnormalities, and soft tissue masses.

PMID- 11331162
TI  - Solitary enchondroma in the distal phalanx of the right thumb. An unusual
      localization.
AB  - An unusual localization of solitary enchondroma in the distal phalanx of the
      right thumb is reported. The lesion was studied by radiograph and magnetic
      resonance imaging (MRI) investigation. It was surgically treated by curettage
      with bone grafting.

PMID- 11331164
TI  - Obstructive sleep apnea and postoperative analgesia--a potentially dangerous
      combination.

PMID- 11331165
TI  - Analgesic effect of epidural neostigmine after abdominal hysterectomy.
AB  - STUDY OBJECTIVE: To evaluate the effects of epidurally administered neostigmine
      on pain after abdominal hysterectomy. DESIGN: Prospective, randomized, double
      blind study. SETTING: Teaching hospital. PATIENTS: 45 ASA physical status I adult
      patients scheduled for abdominal hysterectomy. INTERVENTIONS: All patients
      received identical general and epidural anesthesia. At the end of the surgery,
      they received epidural bupivacaine (10 mg) with either saline (control group, n =
      15), 5 micro g/kg (5-micro g group, n = 15), or 10 micro g/kg neostigmine (10
      micro g group, n = 15). Postoperatively, 50 mg diclofenac suppository was given
      for pain relief on patient demand. MEASUREMENTS AND MAIN RESULTS: The time to
      first diclofenac administration and the number of times diclofenac was required
      during the first 24 postoperative hours were recorded. Pain was assessed using a
      10-cm visual analog pain scale (VAS) at rest at the first diclofenac request, and
      at 15 and 24 hours after surgery. The time to first diclofenac administration was
      significantly longer (p < 0.05) in the 10-micro g group (223 +/- 15 min) than in
      the control (78 +/- 17 min) or 5-micro g groups (88 +/- 18 min). However,
      epidural neostigmine at both doses did not reduce the number of postoperative
      diclofenac administrations. There were no differences in VAS among the three
      groups. CONCLUSIONS: Epidural neostigmine of 10 micro g/kg in bupivacaine
      provides a longer duration of analgesia than does bupivacaine alone or with 5
      micro g/kg of neostigmine after abdominal hysterectomy.

PMID- 11331166
TI  - Effects of trendelenburg position and positive intrathoracic pressure on internal
      jugular vein cross-sectional area in anesthetized children.
AB  - STUDY OBJECTIVE: To compare the cross-sectional area (in cm(2)) of the left
      internal jugular vein (LIJV) and right internal jugular vein (RIJV) in
      anesthetized children, and measure the response to the Trendelenburg tilt
      position (TBRG) and a positive inspiratory pressure hold. DESIGN: Prospective,
      nonrandomized study. SETTING: University medical center. PATIENTS: 45 ASA
      physical status I and II children, ages 6 months to 8 years, undergoing general
      anesthesia and mechanical ventilation. INTERVENTIONS: The cross-sectional area of
      both internal jugular veins was measured with a 5-MHz, two-dimensional surface
      transducer, at the level of the cricoid cartilage. Three measurements were
      obtained: 1) with the patient supine, 2) during a 10-second breath-hold with a
      positive inspiratory pressure (PIP) of 20 cm H(2)O, and 3) with the patient at 20
      degrees TBRG. Data were analyzed with two-way analysis of variance (ANOVA) and
      Student-Newman-Keuls test, with a p < 0.05 considered significant. MEASUREMENTS
      AND MAIN RESULTS: In supine patients, the cross-sectional area of the RIJV was
      larger than the LIJV in 31 patients (69%), and equal or smaller in 14 patients
      (31%) (0.80 +/- 0.38 vs. 0.59 +/- 0.22; p = 0.002). A PIP hold, but not TBRG,
      significantly dilated the RIJV (0.8 +/- 0.38 at baseline vs. 0.93 +/- 0.42 with
      TBRG; p = not significant vs. 1.1 +/- 0.46 with PIP; p < 0.05), whereas neither
      maneuver was effective with the LIJV. CONCLUSION: The cross-sectional area of the
      RIJV is often greater than the LIJV; the TBRG was not effective to increase the
      cross-sectional area of the internal jugular veins, and only a PIP hold increased
      significantly the cross-sectional area of the RIJV. In this study, the LIJV
      appeared of smaller size and less compliant compared with the RIJV.

PMID- 11331167
TI  - Preoperative oral rofecoxib does not decrease postoperative pain or morphine
      consumption in patients after radical prostatectomy: a prospective, randomized,
      double-blinded, placebo-controlled trial.
AB  - STUDY OBJECTIVES: To evaluate the analgesic efficacy of the rofecoxib po before
      radical prostatectomy. DESIGN: Prospective, randomized, double-blinded, placebo
      controlled trial. SETTING: Teaching hospital. PATIENTS: Anesthetic management was
      standardized. Patients received either a 50-mg rofecoxib capsule or a placebo
      capsule po 1 hour before induction of anesthesia. MEASUREMENTS AND MAIN RESULTS:
      Patient-generated 10-cm visual analog scale (VAS) scores for pain were assessed
      at 1, 2, 4, 6, 8, and 24 hours after surgery. Morphine consumption was recorded
      from a patient-controlled analgesia device at the same time. A patient-generated
      overall pain relief score was obtained at 24 hours after surgery. We were unable
      to detect any differences between study groups with respect to postoperative
      morphine consumption, VAS score, or overall pain relief score. CONCLUSIONS: When
      rofecoxib is used po in maximum recommended doses before surgery, it does not
      provide significant analgesia that results in reduction in pain scores or
      analgesic requirements for patients after radical prostatectomy.

PMID- 11331168
TI  - Comparison of fentanyl and sufentanil in combination with bupivacaine for patient
      controlled epidural analgesia during labor.
AB  - STUDY OBJECTIVES: To compare the efficacy of fentanyl plus bupivacaine with
      sufentanil plus bupivacaine for treatment of pain during labor and delivery using
      patient-controlled epidural analgesia (PCEA). DESIGN: Prospective, double-blind,
      clinical investigation. SETTINGS: University-affiliated hospital. PATIENTS: 226
      ASA physical status I and II laboring patients. INTERVENTIONS: Patients were
      randomized to receive 0.125% bupivacaine with fentanyl (2 micro g.ml(-1)) or
      0.125% bupivacaine with sufentanil (0.25 micro g.ml(-1)) through PCEA.
      MEASUREMENTS: Maternal analgesia assessed by visual analog scale was recorded
      before epidural block, 1 and 3 hours after epidural block, at full cervical
      dilation, and at delivery. Motor blockade assessed by Bromage scale was recorded
      at delivery. MAIN RESULTS: Nine patients in group fentanyl, and 11 in group
      sufentanil were excluded from the study. Overall analgesia was good and no
      difference was observed between the two groups. Total boluses of 4 mL bupivacaine
      opioid administered and the number of supplementary top-up injections of 5 mL
      0.25% bupivacaine were similar in both groups. In group sufentanil, motor
      blockade and pruritus were significantly lower than in group fentanyl. Nausea was
      not recorded in any patients. Mode of delivery was similar in both groups, i.e.,
      cesarean section, vacuum or forceps, or spontaneous vaginal delivery. No
      difference was observed in Apgar scores. CONCLUSIONS: Sufentanil is preferable to
      fentanyl during bupivacaine PCEA as there is less incidence of motor blockade and
      pruritus.

PMID- 11331169
TI  - Hydroxyethyl starch (HES) does not directly affect renal function in patients
      with no prior renal impairment.
AB  - STUDY OBJECTIVES: To examine the effects of hydroxyethyl starch (HES) on renal
      function. DESIGN: Randomized, controlled trial. SETTING: Operating theatre of a
      university hospital. PATIENTS: 60 ASA physical status I and II male patients
      undergoing middle ear surgery. INTERVENTIONS: Patients received either lactated
      Ringer's solution (LRS) or one of three HES solutions. The HES solutions were
      administered in a dose of 15 mL/kg bodyweight (bw), the Ringer's solution in a
      dose of 60 mL/kg bw, after induction of anesthesia over a period of one hour.
      MEASUREMENTS: Blood and urine samples for hormone and enzyme tests were obtained
      at defined times before, during, and after surgery. Urine excretion, glomerular
      filtration rate (GFR), renal plasma flow, and routine hemodynamic parameters were
      measured simultaneously. MAIN RESULTS: There were no significant intergroup
      differences regarding GFR, renal plasma flow, or tubular and glomerular integrity
      as measured by specific proteins and enzymes (alpha-1-microglobulin, Tamm
      Horsfall-protein, immunoglobulin G, and N-acetyl-beta-D-glucosaminidase).
      Arginine vasopressin decreased in all groups during and following anesthesia,
      aldosterone and plasma renin activity decreased only in the HES groups, and
      angiotensin II decreased only in the HES 200/0.5 group. Central venous pressure
      increased during fluid administration in the LRS group and returned to baseline
      sooner in the HES groups. CONCLUSIONS: Hydroxyethyl starch administration appears
      to be risk-free with regard to renal function in patients without preexisting
      renal dysfunction who undergo general anesthesia. The relevance of the decrease
      in aldosterone following HES therapy needs further investigation.

PMID- 11331170
TI  - Comparison of cisatracurium-induced neuromuscular blockade between immediate
      postpartum and nonpregnant patients.
AB  - STUDY OBJECTIVES: To evaluate and compare cisatracurium-induced neuromuscular
      blockade and intubating conditions between immediate postpartum (PP) and
      nonpregnant (NP) patients. DESIGN: Prospective control study. SETTINGS:
      University Hospital Center. PATIENTS: 44 ASA physical status I and II patients:
      22 immediate postpartum (PP) patients (<48 hours after delivery) scheduled for
      elective postpartum tubal ligation and 22 nonpregnant (NP) patients (>40 weeks
      from prior pregnancy) scheduled for elective gynecological procedures.
      INTERVENTIONS: General anesthesia was induced intravenously (IV) with thiopental
      sodium 5 mg/kg, fentanyl 2.0 to 3.0 ug/kg, midazolam 0.015 to 0.025 mg/kg, and
      cisatracurium 0.2 mg/kg. Evoked electromyographic responses of the adductor
      pollicis muscle were obtained by supra-maximal train-of-four stimulation of the
      ulnar nerve every ten seconds via surface electrodes at the wrist. Intubation was
      attempted at 90 s after completion of cisatracurium administration and again at
      120 seconds if the first attempt was unsuccessful. The intubating
      anesthesiologist assessed the intubating conditions with four variables: jaw
      relaxation, vocal cord immobility and exposure, patient/diaphragmatic movement,
      and overall intubating impression. Intraoperative anesthetic was maintained with
      30% oxygen, 70% nitrous oxide, and 1% end-tidal isoflurane, as tolerated. Patient
      temperature was maintained at 35.5 degrees to 37.5 degrees Celsius (C), and end
      tidal carbon dioxide at 30 to 36 mmHg. MEASUREMENTS AND MAIN RESULTS: The mean
      onset times to 50%, 90%, and maximal T(1) depression and mean time to 25% T(1)
      recovery in the PP group (68 +/- 19 sec, 110 +/- 26 sec, 147 +/- 32 sec, 60 +/- 6
      min) were significantly less than those in the NP group (80 +/- 17 sec, 131 +/-
      28 sec, 181 +/- 44 sec, 69 +/- 12 min), respectively (p < 0.05). All patients
      were successfully intubated on the first attempt at 90 seconds. 91% of the NP
      group and 81% of the PP group had excellent overall intubating conditions.
      CONCLUSIONS: This is the first published control study to compare the effects of
      cisatracurium between NP and PP patients. The results suggest that the mean onset
      time and clinical duration of cisatracurium are significantly shorter in
      immediate postpartum patients than those in nonpregnant female patients.

PMID- 11331171
TI  - Can estrogen influence the response to noxious stimuli?
AB  - STUDY OBJECTIVES: To evaluate estrogen-induced alternations in noxious stimuli
      response. DESIGN: Randomized, prospective, double-blind study. SETTINGS: Tertiary
      care academic medical center. PATIENTS: 40 ASA physical status I and II women at
      the beginning and conclusion of an in vitro fertilization stimulation cycle.
      INTERVENTIONS: Stimuli were applied to the fingers of the dominant hand via a
      Basile Analgesy-Meter, which applied increasing pressure (g/cm(2)) in a
      continuous fashion, and ice water immersion. MEASUREMENTS: Serum hormonal
      concentrations and responses to noxious (pressure and cold thermal) stimuli were
      studied. MAIN RESULTS: Estrogen and progesterone concentrations changed from 377
      +/- 323.42 pg/mL to 2078.05 +/- 1175.92 pg/mL (p < 0.001) and 1.20 +/- 0.56 to
      1.03 +/- 0.35 ng/mL (p = NS), respectively. Although no significant difference
      was noted in the response to pressure (16.92 +/- 4.41 to 17.85 +/- 4.95 g/cm(2)),
      a significant reduction in the tolerance to ice water immersion (34.18 +/- 28.29
      to 24.05 +/- 23.02 s) was observed. CONCLUSIONS: High estrogen concentrations are
      associated with significantly lower tolerance to cold, but not pressure stimuli.

PMID- 11331172
TI  - Tolerance during sedation in a pediatric ICU patient: effects on the BIS monitor.
AB  - The authors demonstrate the effects of tolerance as measured using the bispectral
      index (BIS) monitor. Over a 5-day period, there was a twofold increase in the
      dose of midazolam and a threefold increase in the dose of fentanyl required to
      provide the same level of sedation and the same BIS number in a 9 year old boy
      receiving sedation during mechanical ventilation.

PMID- 11331173
TI  - Use of a ventilating tube exchanger in patients undergoing tracheostomy: report
      of two cases.
AB  - Two case reports in which a ventilating tube exchanger was used during
      tracheostomy in patients with potential for difficult reintubation are presented.
      We recommend leaving the ventilating tube exchanger in place for 48 hours to
      allow reintubation from above in the event of inadvertent decannulation in cases
      where difficult intubation is anticipated. Ventilating tube exchangers have been
      used to assist in the management of difficult airways in a variety of ways. These
      methods include the use of ventilating tube exchangers as malleable stylets,
      endotracheal tube exchangers and conduits through which oxygen can be delivered.
      We present two cases in which a ventilating tube exchanger was used as an adjunct
      to airway management in a novel fashion.

PMID- 11331174
TI  - Severe methemoglobinemia on reexposure to benzocaine.
AB  - We report a 65-year-old male who developed severe methemoglobinemia only on
      reexposure to benzocaine. The patient needed two awake fiberoptic intubations for
      emergency surgeries. On the second exposure, the patient was septic and
      malnourished, and he was taking acetaminophen. He developed a methemoglobin level
      of 55%. Possible reasons for the methoglobinemia on reexposure are discussed in
      this report.

PMID- 11331175
TI  - An unusual complication during central venous catheter placement.
AB  - A 31-year-old man with disseminated Coccidioides imitis infection required
      central catheter placement for access. The patient had an inferior vena cava
      (IVC) filter placed as a result of previous deep venous thrombosis of the left
      lower extremity. The guidewire could not be removed following placement of the
      right internal jugular catheter by the Seldinger technique. Fluoroscopic
      examination revealed entanglement of the J-tip guidewire in the apex of the IVC
      filter. The catheter was successfully removed by interventional radiologists
      using a snare tip catheter through the left femoral vein.

PMID- 11331176
TI  - Anesthetic management of toxic epidermal necrolysis: report of three adult cases.
AB  - Toxic epidermal necrolysis is a rare but acute life-threatening syndrome in which
      the epidermis blisters and peels in large sheets. In general, patients with this
      syndrome are managed as severe second-degree burn patients, but special
      consideration should be given to mucous membrane involvement that reduces fluid
      intake and worsens the fluid deficit, systemic involvement that makes these
      patients hemodynamically unstable, and progression of cutaneous lesions that
      enhances the risk of infection and sepsis.

PMID- 11331177
TI  - Morbid obesity and the prone position: a case report.
AB  - An improperly positioned prone patient can experience serious impairment of
      cardiopulmonary function. However, with appropriate preparation, even an
      extremely obese patient can safely tolerate the prone position.

PMID- 11331178
TI  - Laryngeal mask airway and high-frequency jet ventilation for the resection of a
      high-grade upper tracheal stenosis.
AB  - The surgical resection of a high-grade tracheal stenosis presents a special case
      of a difficult airway. A 20-year-old male was treated for a 45-mm long tracheal
      stenosis with 60% reduction of the patent airway area beginning 25 mm below the
      glottis. To avoid manipulations of the affected segment before surgical exposure
      of the trachea was established, strictly supraglottic ventilation via a laryngeal
      mask airway was performed. During removal of the stenosis and creation of the
      anastomosis, transglottic high-frequency jet ventilation (HFJV) is a convenient
      technique that enables optimal access to the operation field. Changing from HFJV
      to conventional ventilation after completion of the anastomosis is not necessary,
      and the jet catheter can be left in place until the end of the anesthesia.

PMID- 11331179
TI  - Obstructive sleep apnea in the adult obese patient: implications for airway
      management.
AB  - Obstructive sleep apnea in the adult obese patient may be due, in part, to an
      increased amount of pharyngeal tissue. Therefore, there is an increased risk of
      intubation and extubation difficulties and pain management can be expected to be
      complicated by opioid/sedative-induced pharyngeal collapse.

PMID- 11331181
TI  - Introduction.

PMID- 11331182
TI  - Drosophila as a model to study human brain degenerative diseases.
AB  - Drosophila has been an ideal system in which to identify molecules and define
      pathways involved in development, in part because of the powerful genetic
      approaches that are possible. Many of the molecules and pathways important in
      development in Drosophila are evolutionarily conserved between fly and human.
      With its highly evolved nervous system, amenability to genetic analysis, and the
      full genomic sequence available, Drosophila is a valuable tool for investigating
      and understanding the molecular mechanisms of neurodegenerative diseases.In order
      to have neurodegenerative Drosophila mutants, I screened EMS treated X
      chromosomes and P-element inserted 2nd and 3rd chromosomes in Drosophila for
      reduced life span and neurodegeneration. Twenty-one neurodegenerative mutants
      including bubblegum, spongecake, and eggroll were isolated and were named by
      virtue of their brain lesions. Each mutant has distinct pattern of degeneration
      in specific regions of the brain. Degeneration occurs in lamina and retina region
      in bubblegum. In spongecake vacuolization can only be seen in the optic lobe,
      especially in the medulla region. Multilamellated inclusions are wide-spread in
      the brain of eggroll. It showed not only do the pathologies iin fly brains
      resemble that of human diseases including Creutzfeldt Jakob disease, Tach-Sachs
      and Niemann-Pick disease, but the gene involved in the pathological pathway in
      the bubblegum mutant also functions as in the human adrenoleukodystrophy.

PMID- 11331183
TI  - Drosophila as a genetic approach to human neurodegenerative disease.
AB  - Polyglutamine disease is a class of human neurodegenerative diseases
      characterized by late-onset, progressive neural degeneration. The molecular
      mechanism is expansion, within the coding region of the respective genes, of a
      CAG repeat encoding glutamine. The expanded polyglutamine domain confers dominant
      toxicity on the disease protein, leading to neuronal dysfunction and
      degeneration. In order to develop Drosophila as a model system to approach and
      study such human diseases, a human gene encoding an expanded polyglutamine
      protein was introduced into the fly. Expression of this protein with a pathogenic
      polyglutamine domain causes late-onset, progressive degeneration of cells in the
      fly, as it does in humans with disease and mouse transgenic models. Moreover, the
      protein shows abnormal protein aggregation in flies, similar to human disease
      tissue. These studies indicate that molecular mechanisms of polyglutamine-induced
      neurodegeneration are conserved in Drosophila. Through these studies and
      additional studies to develop fly models for other human neurodegenerative
      diseases, including Parkinson's disease, the power of Drosophila genetics can be
      brought to bear toward the molecular understanding and treatment of human
      neurodegeneration.

PMID- 11331184
TI  - Dopamine signaling in Caenorhabditis elegans-potential for parkinsonism research.
AB  - The nematode Caenorhabditis elegans is an attractive model system for the study
      of many biological processes. It possesses a simple nervous system with known
      anatomy and connectivity, is conveniently and cheaply cultured in the laboratory,
      and is amenable to many genetic manipulations that are impossible in mammalian
      systems. The recent completion of the C. elegans genome sequence provides a rich
      resource of genomic and bioinformatic data to researchers in diverse fields. This
      organism, however, has been underexploited in the studies of many basic processes
      related to nervous system function, neuropsychiatric disorders and neuromuscular
      function. Anatomical, biochemical, behavioral, pharmacological and genetic
      evidence accumulated to date strongly suggests that dopamine is used as a
      neurotransmitter by C. elegans, and that its effects are mediated through
      pathway(s) that share many features with those of mammals. DNA sequence analysis
      reveals genes highly homologous to those encoding mammalian dopamine receptors.
      Probably, C. elegans has dopamine receptors that transduce environmental cues
      into behaviors, and these receptors pharmacologically most closely resemble the
      D2 family. Here we present a review of the current state of research into the
      dopamine system of the worm, focussing on its potential for use in the study of
      biological processes related to parkinsonism.

PMID- 11331185
TI  - C. elegans: a novel pharmacogenetic model to study Parkinson's disease.
AB  - Parkinson's disease (PD) is characterized by the degeneration of dopaminergic
      neurons in the substantia nigra pars compacta. Although the use of vertebrate and
      tissue culture systems continue to provide valuable insight into the pathology of
      the neurodegeneration, the molecular determinants involved in the etiology of the
      disease remain elusive. Because of the high conservation of genes and metabolic
      pathways between invertebrates and humans, as well as the availability of genetic
      strategies to identify novel proteins, protein interactions and drug targets,
      genetic analysis using invertebrate model systems has enormous potential in
      deducing the factors involved in neuronal disease. In this article, we discuss
      the opportunities for the use of the nematode Caenorhabditis elegans (C. elegans)
      for gaining insight into the molecular mechanisms and pathways involved in PD.

PMID- 11331186
TI  - A re-evaluation of the current model of the basal ganglia.
AB  - The current model of basal ganglia organization has been developed progressively
      over the last two decades in the light of key observations made at both
      experimental and clinical levels. This model has been highly successful in that
      it has stimulated a large amount of research in the field. However, several
      experimental and clinical findings that are at odds with the model have
      accumulated during the last decade. This paper reviews some of our own single
      axon tracing studies in primates, which call for a re-evaluation of the current
      basal ganglia model.

PMID- 11331187
TI  - Deep brain stimulation for Parkinson's disease.
AB  - Deep brain stimulation (DBS) is making a major impact in patients with advanced
      Parkinson's disease who continue to be disabled despite the best available
      medical therapy. Stimulation of the internal segment of the globus pallidus (GPi)
      or the subthalamic nucleus (STN) can improve tremor, rigidity, bradykinesia and
      gait disturbances in Parkinson's disease and improve the day-to-day activities of
      patients with these disabling symptoms. While the mechanism of action of DBS
      remains poorly understood, the success of technique in the treatment of movement
      disorders is bringing into question traditional concepts of the organization and
      of the basal ganglia and spearheading a re-examination of the nature and function
      of brain areas involved in the control of movement. Future developments in this
      rapidly advancing area will include the elucidation of the mechanism of action of
      DBS and technical advances in surgical techniques, in electrode design and in
      choosing better stimulation parameters. These advances will improve the scope and
      effectiveness of DBS and expand its clinical indications.

PMID- 11331188
TI  - Cell implantation therapies for Parkinson's disease using neural stem, transgenic
      or xenogeneic donor cells.
AB  - A new therapeutic neurological and neurosurgical methodology involves cell
      implantation into the living brain in order to replace intrinsic neuronal
      systems, that do not spontaneously regenerate after injury, such as the
      dopaminergic (DA) system affected in Parkinson's disease (PD) and aging. Current
      clinical data indicate proof of principle for this cell implantation therapy for
      PD. Furthermore, the disease process does not appear to negatively affect the
      transplanted cells, although the patient's endogenous DA system degeneration
      continues. However, the optimal cells for replacement, such as highly specialized
      human fetal dopaminergic cells capable of repairing an entire degenerated nigro
      striatal system, cannot be reliably obtained or generated in sufficient numbers
      for a standardized medically effective intervention. Xenogeneic and transgenic
      cell sources of analogous DA cells have shown great utility in animal models and
      some promise in early pilot studies in PD patients. The cell implantation
      treatment discipline, using cell fate committed fetal allo- or xenogeneic
      dopamine neurons and glia, is currently complemented by research on potential
      stem cell derived DA neurons. Understanding the cell biological principles and
      developing methodology necessary to generate functional DA progenitors is
      currently our focus for obtaining DA cells in sufficient quantities for the unmet
      cell transplantation need for patients with PD and related disorders.

PMID- 11331189
TI  - Neuroprotective effects of D3 dopamine receptor agonists.
AB  - The effects of D(3) receptor activation are unresolved at this time, but may have
      practical implications in the treatment of Parkinson's disease (PD). As a result
      of assessing the neuroprotective effects of the direct-acting D(3) preferring
      dopamine (DA) agonist pramipexole (PPX), we have observed that drugs which
      psossess D(3) affinity increase the production of a DA neurotrophic factor in
      tissue culture. This molecule is increased by treatment with PPX, is
      constitutively produced by DA neurons in culture, and possesses a molecular
      weight of approximately 35kDa. It is hypothesized that this molecule may be the
      so-called DA autotrophic factor referred to by many authors over the past two
      decades. Interestingly, the protein is oxidant-labile and, therefore, D(3)
      agonists which increase its production and also possess antioxidant capacity
      would provide unique neuroprotective benefits to patients with PD. However, many
      questions remain. Although the data supporting this notion are strong, it is
      clear that other unknown characteristics of DA agonists, including increased
      production of anti-apoptotic proteins, are also involved. This manuscript will
      review this concept in the context of tissue culture strategies of
      neuroprotection. Although no conclusion can be made at this time, it is clear
      that direct comparisons of the neuroprotective effects of direct-acting DA
      agonists in mesencephalic culture can provide considerable insight into the
      mechanistic actions of anti-dopaminergic drugs.

PMID- 11331190
TI  - Ventral striatal D(3) receptors and Parkinson's Disease.
AB  - Antiparkinsonian drugs are thought to act largely through the D2 receptor family
      that includes the D(2) and D(3) receptors. D(2) and D(3) receptors exhibit both
      complementary and overlapping expression at the macro and cellular level. The
      D(3) receptor appears to be a primary target of the mesolimbic dopamine system,
      is highly enriched in expression within the "limbic" striato-pallidal-thalamic
      loop, and is recognized as being regulated by dopaminergic activity in distinctly
      different ways from the D(2) receptor. In Parkinson's Disease it has been
      determined that loss of dopaminergic innervation results in elevation of the D(2)
      receptor but reduced levels of the D(3) receptor. In many late-stage Parkinson's
      Disease patients there is a loss of antiparkinsonian response to L-dopa and other
      antiparkinsonian drugs that is often correlated with clinical signs for dementia.
      We have determined that the reduction of D(3) receptor, and not that of the D(2)
      receptor, is associated with the loss of response to L-dopa and other
      antiparkinsonian drugs. The reduction of D(3) receptor is also related to the
      presence of dementia. An elevation of D(3) receptors was evident in those
      Parkinson's Disease cases with continued good response to L-dopa. Thus, we
      believe that reduced D(3) receptor number is correlated with certain subgroups of
      Parkinson's Disease and may also be related to a further diminishment in the
      mesolimbic DA system.

PMID- 11331191
TI  - The use of pramipexole in Parkinson's disease: are its actions D(3) mediated?
AB  - Pramipexole is a non-ergot dopamine agonist recently approved for the treatment
      of early and advanced Parkinson's disease (PD). It has preferential affinity for
      the D(3) dopamine receptor, compared to previous dopamine agonists that have
      higher affinity for D(2) dopamine receptors. The ultimate question is whether its
      efficacy is linked to its action at the D(3) dopamine site or due to its binding
      to D(2) dopamine receptors. There is no direct experimental evidence available to
      answer this question. Based on a review of the pharmacological literature, it is
      likely that the motor benefits of pramipexole in PD patients are due to D(2)
      stimulation, whereas its putative effects on mood and apathy may be related to
      its D(3) agonist properties.

PMID- 11331192
TI  - Adenosine/dopamine interaction: implications for the treatment of Parkinson's
      disease.
AB  - Evidence for a role of dopaminergic neurotransmission in the motor effects of
      adenosine antagonists, such as caffeine, is reviewed, based on the existence of
      specific antagonistic interactions between specific subtypes of adenosine and
      dopamine receptors in the striatum. Both adenosine A(1) and adenosine A(2A)
      receptor antagonists induce motor activation in rodents. At least a certain
      degree of dopaminergic activity is required to obtain adenosine antagonist
      induced motor activation, with adenosine A(1) antagonists being the most
      sensitive and non-selective adenosine antagonists the most resistant to striatal
      dopamine depletion. When considering long-term treatment with adenosine
      antagonists concomitant administration of dopamine agonists might be required in
      order to obtain strong motor effects (cross-sensitization) and to avoid the
      development of telerance.

PMID- 11331193
TI  - Fullerene-based antioxidants and neurodegenerative disorders.
AB  - Water-soluble derivatives of buckminsterfullerene (C(60)) derivatives are a
      unique class of compounds with potent antioxidant properties. Studies on one
      class of these compounds, the malonic acid C(60) derivatives (carboxyfullerenes),
      indicated that they are capable of eliminating both superoxide anion and
      H(2)O(2), and were effective inhibitors of lipid peroxidation, as well.
      Carboxyfullerenes demonstrated robust neuroprotection against excitotoxic,
      apoptotic and metabolic insults in cortical cell cultures. They were also capable
      of rescuing mesencephalic dopaminergic neurons from both MPP(+) and 6
      hydroxydopamine-induced degeneration. Although there is limited in vivo data on
      these compounds to date, we have previously reported that systemic administration
      of the C(3) carboxyfullerene isomer delayed motor deterioration and death in a
      mouse model of familial amyotrophic lateral sclerosis (FALS). Ongoing studies in
      other animal models of CNS disease states suggest that these novel antioxidants
      are potential neuroprotective agents for other neurodegenerative disorders,
      including Parkinson's disease.

PMID- 11331194
TI  - Parkinson's disease and related neurodegenerative synucleinopathies linked to
      progressive accumulations of synuclein aggregates in brain.
AB  - Parkinson's disease (PD) is the most common neurodegenerative movement disorder
      and the classic clinical-neuropathological features of PD have been well
      established, including many aspects of the morphology and distribution the
      filamentous hallmark intraneuronal inclusions of PD known as Lewy bodies (LBs).
      Nonetheless, the mechanisms underlying brain degeneration in PD are unknown,
      while only partially effective symptomatic treatments for PD are available, and
      there are no known therepeutic interventions that are able to prevent PD or block
      or retard the progression of this relentless disorder. However, dramatic new
      insights into pathobiology of PD have emerged recently with recognition that
      alpha-synuclein abnormalities play a role in the onset and/or progression of PD.
      Moreover, continuing advances in this new research arena provide fresh research
      opportunities to advance understanding of PD, and these novel breakthroughs will
      accelerate discovery of more effective therapies for PD.

PMID- 11331195
TI  - Biochemical changes in multiple system atrophy detected with positron emission
      tomography.
AB  - Multiple system atrophy (MSA) is a sporadic neurodegenerative disorder manifested
      by parkinsonism and dysfunction of autonomic, cerebellar, urinary, and pyramidal
      systems. The most frequent presentation is with a combination of parkinsonism and
      autonomic dysfunction, but cerebellar ataxia with autonomic failure occurs
      frequently as well. Striatonigral degeneration (SND) and sporadic
      olivopontocerebellar atrophy (sOPCA) can progress to include autonomic failure
      and thus may be forms of MSA, but it is not known whether all such cases progress
      to MSA. Utilizing positron emission tomography (PET) with various ligands, my
      colleagues and I have investigated the biochemical changes in sOPCA and MSA to
      understand the relationship between these disorders. An initial study revealed
      decreased local cerebral metabolic rates for glucose in the brainstem,
      cerebellum, putamen, thalamus and cerebral cortex in both MSA and sOPCA,
      suggesting that many sOPCA patients would evolve to develop MSA. Later studies
      confirmed this by demonstrating decreased monoaminergic nigrostriatal terminals
      in both sOPCA and MSA patients. The studies suggest that the ligand used might be
      helpful in determining the risk that an individual patient with sOPCA will
      progress to develop MSA. An investigation of the course of sOPCA patients
      observed clinically over several years revealed that approximately one-fourth of
      them progress to MSA within five years. Studies of gamma-aminobutyric acid type
      A/benzodiazepine neurotransmitter receptors revealed that these sites are largely
      preserved in sOPCA and MSA, indicating that symptomatic pharmacological therapy
      may be possible in these disorders.

PMID- 11331196
TI  - Multiple system atrophy: new developments in pathophysiology and therapy.
AB  - There have been substantial advances in the last five years in understanding the
      basic and clinical pathophysiology underlying multiple system atrophy (MSA).
      Identification of glial cytoplasmic inclusions has been the most important
      organizing principle for further elucidation of underlying mechanisms. Recently,
      several unexpected developments at the clinical level have been reported. In this
      article, we will focus on two of these: (1) the recognition that substantial
      autonomic function is retained in MSA but not modulated appropriately, and (2) a
      potent pressor effect from ingestion of water, which cannot be explained by
      currently understood physiologic and pathophysiologic mechanisms. In some
      patients, water has elicited a 50% increase in blood pressure and been more
      therapeutically effective than any available pressor drug. By careful
      coordination of the pressor effect of water and the depressor effect of
      carbohydrate-rich food, many patients with MSA can now have their blood pressure
      controlled without pharmacological intervention.

PMID- 11331197
TI  - Glutamate is a cotransmitter in ventral midbrain dopamine neurons.
AB  - Interactions between apparently separate dopaminergic and glutamatergic pathways
      figure prominently in the pathophysiology of Parkinson's Disease. So it is
      surprising that the ventral midbrain dopamine neurons, which give rise to the
      dopaminergic pathway, may themselves also be glutamatergic. We have addressed
      this idea in both rat and monkey brain and found that most ventral midbrain
      dopamine neurons exhibit glutamate immunoreactivity. We used postnatal cell
      culture to examine ventral midbrain dopamine neurons more closely. In vitro most
      dopamine neurons exhibit glutamate immunoreactivity, as well as immunoreactivity
      for phosphate-activated glutaminase, the enzyme principally responsible for the
      synthesis of neurotransmitter glutamate; inhibition of glutaminase reduces
      glutamate staining. In single cell microcultures, dopamine neurons make both
      dopaminergic and glutamatergic synaptic varicosities. Stimulation of individual
      dopamine neurons evokes a fast excitatory synaptic response mediated by
      glutamate; it also evokes dopamine release that inhibits the excitatory response
      via presynaptic D2 receptors. Thus, dopamine neurons appear to exert rapid
      synaptic actions via their glutamatergic synapses and slower modulatory actions
      via their dopaminergic synapses, including possibly inhibition of their own
      glutamatergic synapses. So, in the setting of dopamine neuron demise, there will
      be a loss of both dopaminergic and glutamatergic inputs to the striatum;
      furthermore, glutamate released by dopamine neurons may contribute to an
      excitotoxic cascade and the death of neighboring dopamine neurons.

PMID- 11331198
TI  - Endocytosis and downregulation of G protein-coupled receptors.
AB  - The number of G protein-coupled receptors (GPCRs) displayed at the cell surface
      is a critical determinant of physiological responsiveness to native ligands and
      drugs. Downregulation of the number of adrenergic and dopaminergic receptors
      present on specific neurons can be induced by receptor agonists or by drugs that
      increase extracellular concentrations of catecholamines such as dopamine. Thus
      agonist-induced downregulation of GPCRs is of potentially great importance to the
      treatment of Parkinson's Disease. However, little is known about biochemical
      mechanisms that mediate GPCR downregulation. Recent studies of cloned GPCRs have
      provided exciting insights into specific mechanisms that control endocytosis of
      receptors from the plasma membrane and regulate proteolytic degradation of
      receptors. In this review we briefly survey representative studies establishing
      that multiple mechanisms of GPCR membrane trafficking can function in
      downregulation function both in neural and non-neural cell types. Then we focus
      on our present view of mechanisms mediating regulated proteolysis of GPCRs,
      highlighting recent progress in understanding membrane trafficking of GPCRs from
      the cell surface to lysosomes. Finally we discuss emerging evidence regarding a
      specific mechanism that modulates sorting of certain GPCRs between recycling and
      degradative pathways.

PMID- 11331199
TI  - Identification of hypoxia-responsive genes in a dopaminergic cell line by
      subtractive cDNA libraries and microarray analysis.
AB  - Transplantation of dopamine-secreting cells harvested from fetal mesencephalon
      directly into the striatum has had limited success as a therapy for Parkinson's
      disease. A major problem is that the majority of the cells die during the first 3
      weeks following transplantation. Hypoxia in the tissue surrounding the graft is a
      potential cause of the cell death. We have used subtractive cDNA libraries and
      microarray analysis to identify the gene expression profile that regulates
      tolerance to hypoxia. An improved understanding of the molecular basis of hypoxia
      tolerance may allow investigators to engineer cells that can survive in the
      hypoxic environment of the brain parenchyma following transplantation.

PMID- 11331200
TI  - The Ca2+/calmodulin system in neuronal hyperexcitability.
AB  - Calmodulin (CaM) is a major Ca2+-binding protein in the brain, where it plays an
      important role in the neuronal response to changes in the intracellular Ca2+
      concentration. Calmodulin modulates numerous Ca2+-dependent enzymes and
      participates in relevant cellular functions. Among the different CaM-binding
      proteins, the Ca2+/CaM dependent protein kinase II and the phosphatase
      calcineurin are especially important in the brain because of their abundance and
      their participation in numerous neuronal functions. Therefore, the role of the
      Ca2+/CaM signalling system in different neurotoxicological or neuropathological
      conditions associated to alterations in the intracellular Ca2+ concentration is a
      subject of interest. We here report different evidences showing the involvement
      of CaM and the CaM-binding proteins above mentioned in situations of neuronal
      hyperexcitability induced by convulsant agents. Signal transduction pathways
      mediated by specific CaM binding proteins warrant future study as potential
      targets in the development of new drugs to inhibit convulsant responses or to
      prevent or attenuate the alterations in neuronal function associated to the
      deleterious increases in the intracellular Ca2+ levels described in different
      pathological situations.

PMID- 11331201
TI  - Alcohol myopathy: impairment of protein synthesis and translation initiation.
AB  - Alcohol consumption leads to numerous morphological, biochemical and functional
      changes in skeletal and cardiac muscle. One such change observed in both tissues
      after either acute alcohol intoxication or chronic alcohol consumption is a
      characteristic decrease in the rate of protein synthesis. A decrease in
      translation efficiency appears to be responsible for at least part of the
      reduction. This review highlights advances in determining the molecular
      mechanisms by which alcohol impairs protein synthesis and places these
      observations in context of earlier studies on alcoholic myopathy. Both acute and
      chronic alcohol administration impairs translational control by modulating
      various aspects of peptide-chain initiation. Moreover, this alcohol-induced
      impairment in initiation is associated with a decreased availability of
      eukaryotic initiation factor (eIF) 4E in striated muscle, as evidenced by an
      increase in the amount of the inactive eIF4E.4E-BP1 complex and decrease in the
      active eIF4E.eIF4G complex. In contrast, alcohol does not produce consistent
      alterations in the control of translation initiation by the eIF2 system. The
      etiology of these changes remain unresolved. However, defects in the availability
      or effectiveness of various anabolic hormones, particularly insulin-like growth
      factor-I, are consistent with the alcohol-induced decrease in protein synthesis
      and translation initiation.

PMID- 11331202
TI  - Protective effect of vitamin E, beta-carotene and N-acetylcysteine from the brain
      oxidative stress induced in rats by lipopolysaccharide.
AB  - The major goal of this study was to examine the ability of several antioxidants
      namely, vitamin E, beta-carotene and N-acetylcysteine, to protect the brain from
      oxidative stress induced by lipopolysaccharide (LPS, endotoxin). LPS, a component
      of the bacterial wall of gram-negative bacteria, has been recognized as one of
      the most potent bacterial products in the induction of host inflammatory
      responses and tissue injury and was used in this study to mimic infections. LPS
      injection resulted in a significant increase in the stress indices, plasma
      corticosterone and glucose concentration, a significant alteration of the brain
      oxidative status observed as elevation of the level of malondialdehyde (MDA,
      index of lipid peroxidation) and reduction of reduced glutathione (GSH), and a
      disturbance in the brain energy metabolism presented as a reduction in the
      ATP/ADP ratio and an increase in the mitochondrial/cytosolic hexokinase ratio.
      However, the activities of brain superoxide dismutase and Na+, K+-ATPase and
      contents of cholesterol and phospholipids were not altered. Administration of the
      aforementioned antioxidants prior to LPS injection ameliorated the oxidative
      stress by reducing levels of MDA, restoring GSH content and normalizing the
      mitochondrial/cytosolic hexokinase ratio in the brain in addition to lowering
      levels of plasma corticosterone and glucose. In conclusion, this study showed the
      increased free radical generation during infections and LPS-induced stress. It
      also suggests that brain oxidative status and energy is disturbed.

PMID- 11331203
TI  - Purification and characterization of a potent homodimeric guanine-specific
      ribonuclease from fresh mushroom (Pleurotus tuber-regium) sclerotia.
AB  - From the fresh sclerotia of the mushroom Pleurotus tuber-regium, a potent
      homodimeric ribonuclease exhibiting a molecular weight of 29 kDa in FPLC-gel
      filtration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis was
      isolated. The protein was unadsorbed on DEAE-cellulose and adsorbed on Affi-gel
      blue gel, CM-cellulose and Mono S. It manifested strong ribonucleolytic activity
      toward Poly G, slight activity toward Poly U and Poly A, and minimal activity
      toward Poly C. Its optimal pH was determined to be 6.5 when yeast transfer RNA
      was used as substrate. Its ribonucleolytic activity was resistant to heating at
      100 degrees C for 30 min but was inhibited by a number of salts. The protein
      inhibited cell-free translation in a rabbit reticulocyte lysate with an IC50 of
      0.09 nM. Three out of the four amino acid residues at the active site (positions
      38-41) of P. ostreatus ribonuclease, YNNF, were also found at positions 17-20 in
      the P. tuber-regum RNase. However, unlike P. ostreatus RNase, no cysteine
      residues were detected in the N-terminal sequence.

PMID- 11331204
TI  - Analysis of epidermal-type transglutaminase (TGase 3) expression in mouse tissues
      and cell lines.
AB  - In the formation of the cornified cell envelope in the epidermis, epidermal-type
      transglutaminase (TGase 3) cross-links a variety of structural proteins. However,
      its expression in other tissue has not been investigated. Furthermore, no cell
      line expressing TGase 3 has been found. The tissue distribution of TGase 3 in
      mice was investigated using reverse-transcription polymerase chain reaction (RT
      PCR) and Western blotting analyses. TGase 3 mRNA was expressed in the brain,
      stomach, spleen, small intestine, testis, skeletal muscle and skin. The stomach
      and testis expressed TGase 3 protein in size similar to that observed in the
      epidermis. Screening various cell lines, a gastric human cancer cell line, MKN-1
      and mouse neuroblast cell line, neuro2a, were found to express TGase 3.

PMID- 11331206
TI  - Abnormal ornithine decarboxylase activity in transgenic mice increases tumor
      formation and infertility.
AB  - A transgenic mouse line carrying ornithine decarboxylase cDNA as the transgene
      under the control of a mouse mammary tumor virus long terminal repeat (MMTV LTR)
      promoter was generated in order to study whether ornithine decarboxylase
      transgene expression will have any physiological or pathological effect during
      the entire life of a transgenic mouse. The high frequency of infertile animals
      and the loss of pups made the breeding of homozygous mice unsuccessful. However,
      a colony of heterozygous transgenic mice was followed for 2 years. In adult
      heterozygous transgenic mice, ornithine decarboxylase activity was significantly
      increased in the testis, seminal vesicle and preputial gland when compared to non
      transgenic controls. In contrast, ornithine decarboxylase activity was decreased
      in the kidney and prostate of transgenic mice. No significant changes in
      ornithine decarboxylase activity were found in the ovary and mammary gland and
      only moderate changes in ornithine decarboxylase activity were detected in the
      heart, brain, pancreas and lung. The most common abnormalities found in adult
      animals (12 males and 20 females) of the transgenic line were inflammatory
      processes, including pancreatitis, hepatitis, sialoadenitis and pyelonephritis.
      Spontaneous tumors were observed in eight animals, including two benign tumors
      (one dermatofibroma, one liver hemangioma) and six malignant tumors (one
      lymphoma, one intestinal and three mammary adenocarcinomas and one adenocarcinoma
      in the lung). No significant pathological changes were found in 17 nontransgenic
      controls.

PMID- 11331205
TI  - Hypothyroidism provides resistance to reperfusion injury following myocardium
      ischemia.
AB  - A growing body of evidence has demonstrated that reperfusion injury may be
      mediated, in part, by mitochondrial Ca2+ overload that promotes non-selective
      permeability of the inner membrane. In this regard it is known that mitochondria
      from hypothyroid rats are resistant to membrane damage as induced by Ca2+. The
      purpose of this study was to evaluate the sensitivity of hearts from hypothyroid
      rats, to the damage by reperfusion, after an ischemic period of 5 min. The
      results were compared with those from control and hyperthyroid rats.
      Hypothyroidism was established by surgical removal of the thyroid gland; in turn
      hyperthyroidism was induced after a daily injection of 2 mg/kg of 3,5,3'
      triiodothyronine for 4 days. ECG tracings from hypothyroid rats showed a total
      absence of post-reperfusion arrhythmias conversely to what was observed in
      control and hyperthyroid rats. The release of creatine kinase and aspartate amino
      transferase to the plasma in hypothyroid rats was found to be lower than that
      found in hyperthyroid and euthyroid rats. The histological studies showed that
      myocardial fibers from hypothyroid rats were in good condition and retained their
      striae and a remarkable near absence of edema was clearly observed.

PMID- 11331207
TI  - Type VIII collagen: heterotrimeric chain association.
AB  - Two chains, alpha1(VIII) and alpha2(VIII), have been described for type VIII
      collagen. Early work suggested that these chains were present in a 2:1 ratio,
      although recent work has shown that homotrimers can form and predominate in some
      tissues. In order to address the question of whether the alpha1(VIII) and
      alpha2(VIII) chains could co-polymerise we made a shortened alpha1(VIII) chain
      and expressed this with full length alpha2(VIII) chain in an in vitro translation
      system supplemented with semi-permeabilised cells. Heterotrimers containing
      either two or one alpha2(VIII) were evident. Interestingly, a point mutation in
      the NC1 domain of the alpha1(VIII) chain abrogated trimer formation. In addition
      we were able to demonstrate chain association of the alpha1(X) chain of type X
      collagen with the shortened alpha1(VIII) chain. Variations in chain association
      were seen when altered ratios of message were used. These results demonstrate the
      importance of the NC1 domain in chain association and suggest that gene
      expression regulates the composition and function of type VIII collagen by
      varying chain composition.

PMID- 11331208
TI  - Identification of glycogen phosphorylase and creatine kinase as calpain
      substrates in skeletal muscle.
AB  - The goal of this study was to identify calpain substrates in muscle cells. Our
      hypothesis was that the yeast two-hybrid method could be used to identify novel
      calpain substrates. To accomplish this, native mu- and m-calpains, as well as a
      variety of calpain DNA fragments, were expressed in yeast cells and used to
      screen for binding proteins in a human skeletal muscle cDNA library. Calpain
      constructs that were used in the screening process included native mu- and m
      calpains, a dominant negative (DN) m-calpain (i.e. active site modified), N
      terminal truncated DN m-calpain (i.e. autolyzed DN-m-calpain) and, finally, an N-
      and C-terminal truncated m-calpain (i.e. autolyzed DN-m-calpain lacking a calcium
      binding domain). Yeast cells were transformed using yeast two-hybrid expression
      vectors containing the different calpain constructs as "baits". Beta
      galactosidase activity was assayed as an index of interaction between calpain and
      its potential target proteins. From this analysis, four clones (Ca2+-ATPase,
      novel nebulin-related protein (N-RAP), creatine kinase and glycogen
      phosphorylase) were recovered. Two of these, creatine kinase and glycogen
      phosphorylase, were selected for further study. In in-vitro assays, calpain was
      able to partially digest both proteins, suggesting that both creatine kinase and
      glycogen phosphorylase are natural calpain substrates.

PMID- 11331209
TI  - A nuclear receptor in thyroid malignancy: is PAX8/PPARgamma the Holy Grail of
      follicular thyroid cancer?

PMID- 11331210
TI  - Common variants in the regulatory region of the insulin gene are associated with
      fasting plasma insulin levels in juvenile obesity.

PMID- 11331211
TI  - Variations in urinary iodine excretion and thyroid function. A 1-year study in
      healthy men.
AB  - OBJECTIVE: The iodine intake level in a population is determined in cross
      sectional studies. A fraction of samples with iodine content below a certain
      level, e.g. 25 microg/l, may suggest iodine deficiency in part of the population.
      However, urinary iodine varies considerably from day to day and the fraction of
      low samples caused by dispersion remains unsettled. DESIGN: A longitudinal study
      of 16 healthy men living in an area of mild to moderate iodine deficiency.
      METHODS: We measured urinary iodine and creatinine concentrations, and serum TSH,
      total thyroxine (T4), free T4 index and total tri-iodothyronine (T3) in samples
      collected monthly for 1 year. RESULTS: Average urinary iodine excretion was 57.0
      microg/l (49.1 microg/24 h (corrected for creatinine excretion)) and varied from
      29 to 81 microg/l (28 to 81 microg/24 h) between participants. Individual samples
      varied between 10 and 260 microg/l, and the variation around the mean was 2.4
      times larger when calculated for the 180 individual samples compared with the 15
      average annual values (1.7 times larger for estimated 24 h iodine excretion
      values). The fraction of individual samples below 25 microg/l was 6.7% (7.2% < 25
      microg/24 h), whereas none of the participants had average iodine excretion below
      25 microg/l or 25 microg/24 h. Participants with average annual iodine excretion
      below 50 microg/24 h had a negative correlation between iodine excretion and TSH,
      whereas a positive correlation was observed when average annual iodine excretion
      was above this level. CONCLUSIONS: Seven per cent of individual urine samples
      indicated severe iodine deficiency without this being present in the group
      studied. Dispersion was reduced by 24% when using estimated 24 h urinary iodine
      excretion rather than urinary iodine concentration. Participants with moderate
      iodine deficiency (average annual urinary iodine excretion 25-50 microg/24 h)
      showed clear signs of substrate deficiency for thyroid hormone synthesis while
      participants with mild iodine deficiency (50-100 microg/24 h) did not.

PMID- 11331212
TI  - Presentation of a kindred with familial medullary thyroid carcinoma and Cys611Phe
      mutation of the RET proto-oncogene demonstrating low grade malignancy.
AB  - OBJECTIVE: Both multiple endocrine neoplasia type 2A (MEN 2A) and familial
      medullary thyroid carcinoma (FMTC) are caused by germline mutations of the RET
      proto-oncogene. A broad spectrum of malignancy within and between families has
      been described with no clear genotype-phenotype correlation due to a scarcity of
      available data of large kindreds. DESIGN: Here we present the only known family
      with a germline mutation of codon 611 TGC to TTC (exon 10) in the RET proto
      oncogene leading to a replacement of cysteine by phenylalanine (Cys611Phe or
      C611F). RESULTS: Twenty family members of this large kindred are gene carriers
      (GCs) and seven (5-13 years old) are potential carriers but have yet to be
      analysed. The clinical course of medullary thyroid carcinoma (MTC) in this family
      is characterized by a very slow evolution and progression of the tumour with no
      MTC-related death to date. Of 11 patients (30-69 years old) having undergone
      thyroidectomy six were classified as pT1, four as pT2 and one as C-cell
      hyperplasia according to the TNM system of the International Union Against
      Cancer. Due to cervical and mediastinal lymph node metastasis one patient (44
      years old) had to be operated on a second time. The seven non-operated GCs of the
      fourth and fifth generation (17-26 years old) are yearly monitored with
      pentagastrin stimulation tests; one non-operated GC (43 years old) has refused
      any further investigations. Screening for primary hyperparathyroidism and
      phaeochromocytoma was negative in all cases. CONCLUSION: We suggest from these
      experiences that the general advice for thyroidectomy in early childhood should
      be modified in certain families, depending on genotype.

PMID- 11331214
TI  - Development of the parafollicular cells in recurrent goiter.
AB  - OBJECTIVE: To provide more data for the discussion on whether thyroid hormones,
      iodide and other factors controlling the thyroid also influence the
      parafollicular (PF) cells, as the answer is of great importance for optimization
      of the medical treatment of medullary thyroid carcinoma (MTC) after surgery.
      DESIGN: We compared the density of the PF cells in patients who underwent surgery
      for the second time due to recurrent goiter with that in normal-sized thyroid
      glands after the first operation. METHODS: In 20 patients with only one
      operation, all specimens were taken from morphologically and functionally normal
      lobular thyroid parenchyma. The second group consisted of 30 patients who had
      already undergone a nearly total resection of at least one thyroid lobe several
      years before. Then another surgery of the same side was performed due to
      recurrent goiter. Immunohistochemical staining of the PF cells was performed
      using primary antibodies to calcitonin and chromogranin. RESULTS: An average of
      78 PF cells (median 12.5) was found in the sections with the highest density of
      the first group. The average number of PF cells in the second group was just 5
      (median 0). The Wilcoxon test revealed a highly significant difference in the
      total PF cell content between the groups (P < 0.001). CONCLUSIONS: Our study
      suggests that the stimulating factors that lead to growth of the thyroid
      parenchyma do not influence the PF cells. Hence a non-suppressive thyroid hormone
      replacement seems to be sufficient after resection of an MTC.

PMID- 11331213
TI  - Effects of l-thyroxine administration, TSH-receptor antibodies and smoking on the
      risk of recurrence in Graves' hyperthyroidism treated with antithyroid drugs: a
      double-blind prospective randomized study.
AB  - OBJECTIVE: In Graves' hyperthyroidism treated with antithyroid drugs (ATD), the
      overall relapse rate reaches 30-50% following ATD discontinuation. Conflicting
      results have previously been reported with regard to the usefulness of combining
      ATD with thyroxine (l-T4), and thereafter maintaining l-T4 treatment after ATD
      withdrawal. Also, clinicians are in search of useful parameters to predict the
      risk of a recurrence of hyperthyroidism after ATD treatment. DESIGN: Eighty-two
      consecutive patients (70 women and 12 men; mean age 36 years) with a first
      episode of Graves' hyperthyroidism were investigated prospectively; they were
      treated with ATD for a total of 15 months, combined with l-T4 (for at least 12
      months) after they had reached euthyroidism, with the aim of maintaining serum
      TSH below 2.5 mU/l during the combined therapy. Following ATD discontinuation,
      the patients were randomly assigned (double-blind placebo-controlled trial) to
      taking 100 microg/day l-T4 (vs placebo) for an additional year. METHODS: The
      following determinations were carried out at initial diagnosis: serum total T4
      and tri-iodothyronine (T3), free T4 and T3, TSH, TSH-receptor antibodies (TSHR
      Ab), thyroid scintigraphy and echography. During ATD treatment, serum free T4 and
      T3 and TSH concentrations were recorded after 1 (optional), 2, 4, 6, 9, 12 and 15
      months, and echography at the end of ATD treatment. During the randomized trial,
      serum free T4 and T3 and TSH concentrations were checked every 3 months (or until
      a recurrence). TSHR-Ab titers were measured at initial diagnosis, after 6 months
      with ATD, and at the end of ATD treatment. RESULTS: l-T4 administration, both
      during and after ATD treatment, did not improve the final outcome and recurrence
      rates were similar in placebo and l-T4-treated patients (30%). Two parameters
      were identified that might be useful to help predict recurrence risks after ATD:
      (i) positive TSHR-Ab (at the end of ATD treatment) was significantly associated
      with a greatly increased recurrence risk; and (ii) despite the relatively small
      number of patients who were smokers, regular cigarette smoking was shown, for the
      first time, to be significantly associated with an increased recurrence risk.
      Also, the deleterious effect of smoking was shown to manifest its impact
      independently of TSHR-Ab titers at the end of ATD treatment. Thus, compared with
      the overall 30% recurrence risk, non-smoking patients with a negative TSHR-Ab (at
      the end of ATD) had a lower (18%) recurrence risk; smoking patients with negative
      TSHR-Ab (at the end of ATD) had a 57% recurrence risk; non-smoking patients with
      positive TSHR-Ab (at the end of ATD) had a high (86%) recurrence risk; the
      recurrence risk was 100% in those few patients who both smoked and maintained a
      positive TSHR-Ab at the end of ATD treatment. CONCLUSIONS: The present study
      confirmed that l-T4 administration during and after ATD withdrawal did not
      improve remission rate. Two factors, namely positive TSHR-Ab at the end of ATD
      treatment and regular smoking habits may represent clinically useful (albeit not
      absolute) predictors of the risk of recurrence in patients with Graves'
      hyperthyroidism treated with ATD. However, due to the relatively small number of
      smoking patients in the present cohort, this conclusion needs to be confirmed by
      a larger study.

PMID- 11331215
TI  - Craniofacial abnormalities and their relevance for sleep apnoea syndrome
      aetiopathogenesis in acromegaly.
AB  - OBJECTIVE: To explain the effect of craniofacial relations on the development of
      the sleep apnoea syndrome (SAS) in acromegaly, and to elucidate how the activity
      of acromegaly affects the severity of SAS. DESIGN: Prospective observational
      study. METHODS: Cephalometry and sleep ventilation measurements were performed in
      26 acromegalic men and in 96 men with SAS. RESULTS: SAS was found in 20
      acromegalic men. Compared with non-acromegalic men with SAS, patients with
      acromegaly and SAS were found to have: enlargement of almost all linear
      dimensions; increased angle indicating mandibular protrusion; increased
      difference between maxillary and mandibular protrusion; articular angle decrease;
      soft palate lengthening; and pharyngeal airway space (PAS) enlargement in the
      palatal and uvular-tip planes. A comparison of acromegalic men with and without
      SAS revealed no significant difference in the craniofacial skeleton, although
      there was a narrowing of the minimal PAS (MinPAS) and of PAS in the uvular-tip
      plane in patients with SAS. SAS was more frequent in the patients with active
      acromegaly. MinPAS in the patients with active acromegaly was narrower than in
      those without disease activity. CONCLUSION: Skeletal abnormalities in acromegalic
      men with SAS were different from those in SAS patients without acromegaly. Upper
      airway narrowing due to changes in pharyngeal soft tissues takes a more relevant
      share in the development of SAS in acromegalic men than skeletal anomalies.

PMID- 11331216
TI  - Inferior petrosal sinus sampling in the differential diagnosis of Cushing's
      syndrome: results of an Italian multicenter study.
AB  - OBJECTIVE: To evaluate the diagnostic accuracy of inferior petrosal sinus
      sampling (IPSS) in the differential diagnosis of ACTH-dependent Cushing's
      syndrome as compared with pituitary imaging techniques. DESIGN AND METHODS: We
      retrospectively studied the diagnostic accuracy of basal and post corticotropin
      releasing hormone (CRH) IPSS, magnetic resonance imaging and computed tomography
      in distinguishing pituitary from ectopic ACTH secretion in 97 Cushing's syndrome
      patients: 74 with Cushing's disease (CD) and 10 with ectopic ACTH secretion
      (EAS). Thirteen patients were excluded because of unconfirmed diagnosis. The
      difference between IPSS and pituitary imaging techniques in the correctly
      localized pituitary adenoma in the patients with CD was also investigated.
      RESULTS: The basal ACTH inferior petrosal sinus:periphery (IPS:P) ratio was > or
      = 2 in 63/74 patients with CD (85%), and in 1/10 EAS patients (10%); after
      stimulation with CRH, the ratio was > or = 3 in 60/68 patients with CD (88%) and
      < 3 in all patients with EAS. The basal and post-CRH ACTH IPS:P ratios had a
      diagnostic accuracy of 86% and 90% respectively. The diagnostic accuracy of IPSS
      with both ratios was significantly higher than magnetic resonance imaging (50%)
      and computed tomography (40%). The IPS:P ratio suggested by receiver-operator
      characteristic (ROC) analysis that better distinguished CD from EAS was 2.10 for
      the basal and 2.15 for the post-CRH ratios. Using these cut-offs, the specificity
      of basal ratio and the sensitivity of the post-CRH test rose to 100% and 93%
      respectively. Diagnostic accuracy remained substantially unchanged for the basal
      ratio (87% vs 86%), while it rose from 90% to 94% for the post-CRH ratio. The
      sensitivity of IPSS was significantly higher than that of magnetic resonance and
      computerized tomography. IPSS was less reliable in identifying the adenoma site
      found at surgery than magnetic resonance imaging or computed tomography (65% vs
      75% and 79% respectively). CONCLUSION: In conclusion, IPSS improved the
      diagnostic performance of imaging techniques. It can help in excluding
      transsphenoidal surgery in EAS patients. More striking results were obtained when
      a > or = 2.1:1 basal ratio or a > or = 2.15:1 post-CRH ratio were considered as
      criteria to distinguish between patients with CD and EAS. To establish correctly
      the location of the pituitary adenoma, IPSS is less reliable than imaging
      techniques.

PMID- 11331217
TI  - Insulin, leptin, IGF-I and insulin-dependent protein concentrations after insulin
      sensitizing therapy in obese women with polycystic ovary syndrome.
AB  - OBJECTIVE: To determine the clinical, hormonal and biochemical effect of 4-5
      months of insulin-sensitizing therapy (hypocaloric diet+metformin) in obese
      patients with polycystic ovary syndrome (PCOS). DESIGN: Prospective study.
      METHODS: Twenty-three obese patients with PCOS, 19 obese patients without
      menstrual disturbances and 11 healthy control women were recruited from the
      Department of Endocrinology and Endocrine Gynecology, Medical Academy, Bialystok,
      Poland. Obese patients received 500 mg metformin together with hypocaloric diet
      three times daily for 4-5 months, after baseline study. The clinical parameters,
      menstrual pattern and serum concentrations of insulin, leptin, IGF-I, insulin
      dependent proteins (sex hormone-binding protein (SHBG), insulin-like growth
      factor-binding protein-1 (IGFBP-1)), gonadotropins and sex steroids were
      determined before and after treatment. RESULTS: In the baseline study, obese
      patients with PCOS had significantly higher insulin, testosterone and LH
      concentrations in comparison with the other groups. The serum leptin, IGF-I,
      IGFBP-1 and SHBG were not different between the two groups of obese patients, but
      there was a significant difference in comparison with the control group. After
      metformin therapy a significant reduction in BMI, % of body fat and leptin
      concentration were observed in both groups of obese patients. Fasting insulin,
      testosterone and LH concentrations decreased significantly only in the PCOS
      group. Six out of 11 patients in the PCOS group had more regular menstrual
      cycles; two patients conceived. CONCLUSIONS: Insulin-sensitizing therapy could be
      considered as an additional therapeutic option in obese women with PCOS.

PMID- 11331218
TI  - Adrenomedullin, a new peptide, in patients with insulinoma.
AB  - BACKGROUND: It has been demonstrated that adrenomedullin, a newly discovered
      peptide, affects the release of insulin from pancreatic islets cells, suggesting
      a role in the insulin-regulating system. OBJECTIVE: To investigate whether
      adrenomedullin secretion is modified in patients with insulin-secreting islet
      cell tumours. DESIGN: The study was performed in nine patients with surgically
      treated insulinoma. Circulating adrenomedullin was assayed using a specific
      radioimmunoassay and its localization and distribution in the tumour were
      determined by means of immunohistochemistry. RESULTS: Adrenomedullin
      concentrations were significantly greater in patients with insulinoma (6.6 +/-
      3.2 fmol/ml) than in controls (2.1 +/- 1.1 fmol/ml). In six patients monitored
      before and after surgery, plasma adrenomedullin decreased from 6.3 +/- 2.9
      fmol/ml to 3.0 +/- 1.6 fmol/ml. Immunoreactive adrenomedullin was localized
      exclusively in the tumours cells, whereas stroma, surrounding pancreas parenchyma
      and major ducts were negative for the peptide. CONCLUSIONS: Our findings indicate
      that circulating adrenomedullin is increased in insulinoma and that this increase
      is related to the neoplastic phenotype.

PMID- 11331219
TI  - Influence of a high-fat diet during chronic hyperglycemia on beta-cell function
      in pancreatic islet transplants to streptozotocin-diabetic rats.
AB  - Chronically elevated non-esterified fatty acids (NEFAs) can exert negative
      effects on beta-cell function both in vitro and in vivo. Negative effects of
      fatty acids have been difficult to evaluate in overt diabetes because of the
      attendant hyperglycemia that gives rise to the confounding influence of
      'glucotoxicity'. In this work, we tested for the effects of NEFAs in diabetes by
      (i) taking into account potential effects of prevailing levels of hyperglycemia,
      and (ii) focusing on lingering (and therefore possibly more serious) effects. A
      diabetic transplantation model was used in which two islet grafts with 200 and 20
      rat islets respectively were transplanted under the kidney capsule of syngeneic
      recipients previously made diabetic by streptozotocin injection. Rats were then
      fed either a high-fat or a low-fat diet for 7 weeks, followed by 1 week of normal
      laboratory chow. During dietary intervention, food was consumed ad libitum in one
      protocol, but was restricted in the low-fat group in a second protocol (in order
      to match blood-glucose levels). A high-fat diet did not affect body weight. At
      the end of the protocols, graft-bearing kidneys were isolated and perfused.
      Insulin responses to 27.8 mM glucose in perfusion were uniformly absent, in
      keeping with previously documented effects of chronic hyperglycemia. In contrast,
      10 mM arginine induced a marked increase in insulin secretion after a low-fat
      diet, an effect that was significantly reduced after a high-fat diet (109 +/- 39
      vs 13 +/- 15 fmol/min (P < 0.05) and 95 +/- 18 vs 32 +/- 5 fmol/min (P < 0.05) in
      the 2 protocols respectively). Regardless of protocol, no effect of diet could be
      detected on graft contents of insulin or preproinsulin mRNA. Thus, under
      conditions in which influences of chronic hyperglycemia could be accounted for, a
      previous high-fat diet with elevated NEFAs inhibited arginine-induced insulin
      secretion; however, the results indicate that insulin biosynthesis and/or beta
      cell mass were not affected.

PMID- 11331220
TI  - The decrease in hepatic IGF-I gene expression in arthritic rats is not associated
      with modifications in hepatic GH receptor mRNA.
AB  - OBJECTIVE: Adjuvant-induced arthritis induces a catabolic response, and a
      decrease in circulating IGF-I. Hypermetabolism and GH insensitivity have been
      described in acute inflammation. The aim of this study was to analyze whether
      impaired IGF-I secretion in arthritic rats can be attributed to hepatic GH
      resistance. DESIGN AND METHODS: Male Wistar rats were injected with complete
      Freund's adjuvant, and 14 days afterwards arthritic and control rats were
      injected daily with recombinant human GH (rhGH) (3 IU/kg) or saline for 8 days.
      GH receptor (GHR) gene expression in the liver and the effect of rhGH on hepatic
      IGF-I synthesis in arthritic rats were examined. RESULTS: There was a significant
      decrease in hepatic concentrations of IGF-I (P < 0.01) as well as in the IGF-I
      gene expression in arthritic but not in pair-fed rats. In contrast, arthritis did
      not modify GHR mRNA levels in the liver. The 8 day administration of rhGH
      resulted in an increase in body weight gain in arthritic but not in control rats.
      There was an increase in hepatic IGF-I synthesis and in GHR mRNA levels after
      rhGH treatment, both in control and in arthritic rats. Two endotoxin
      lipopolysaccharide (LPS) (1 mg/kg) injections decreased hepatic concentrations of
      IGF-I and IGF-I mRNA (P < 0.01). Contrary to the results obtained in arthritic
      rats, mRNA expression of GHR in the liver was lower in LPS- than in saline
      treated rats (P < 0.01). CONCLUSION: These data suggest that the decrease in IGF
      I synthesis induced by chronic arthritis is not secondary to GH resistance.

PMID- 11331221
TI  - 5-HT1 and 5-HT2 receptor agonists blunt +/- -alpha-amino-3-hydroxy-5
      methylisoxazole-4-propionic acid (AMPA)-stimulated GH secretion in prepubertal
      male rats.
AB  - OBJECTIVE: Excitatory amino acids, gamma-amino butyric acid (GABA), serotonin and
      catecholamines are involved in the control of GH secretion. The actions of these
      neurotransmitters are interconnected, and recently we showed that the stimulatory
      effect of GABA was blocked by MK-801, an antagonist of N-methyl-D-aspartate
      receptors. The present experiments were carried out to analyze the
      interrelationships between +/- -alpha-amino-3-hydroxy-5-methylisoxazole-4
      propionic acid (AMPA) receptors and serotoninergic and catecholaminergic pathways
      in the control of GH secretion in prepubertal (16-23-day-old) male rats. DESIGN
      AND METHODS: The GH response to AMPA was analyzed in animals pretreated with 5
      hydroxytryptophan methyl ester (5-HTP) plus fluoxetine (a precursor of 5
      hydroxytryptamine (5-HT) synthesis and a blocker of 5-HT re-uptake), R (+)-8
      hydroxydipropylaminotetralin hydrobromide (8-OH-DPAT, an agonist of the 5-HT1
      receptors), +/- -2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI) and alpha
      methyl-5-hydroxytryptamine (agonists of 5-HT2 receptors), I-phenylbiguanide (an
      agonist of 5-HT3 receptors), or alpha-methyl-p-tyrosine (alpha-MPT) and
      diethyldithiocarbamate (DDC) (blockers of catecholamine synthesis). RESULTS:
      Basal GH secretion remained unchanged in prepubertal rats after activation of the
      serotoninergic system or blockade of catecholamine synthesis. The stimulatory
      effect of AMPA on GH secretion was blocked after activation of the serotoninergic
      system, through specific 5-HT1 and 5-HT2 receptor agonists. In contrast,
      activation of 5-HT3 receptors potentiated AMPA-stimulated GH secretion.
      CONCLUSIONS: Serotoninergic receptors modulate the stimulatory effect of AMPA on
      GH secretion in prepubertal male rats.

PMID- 11331222
TI  - Potentiation response of cultured human uterine leiomyoma cells to various growth
      factors by endothelin-1: role of protein kinase C.
AB  - OBJECTIVE: Factors responsible for the abnormal proliferation of myometrial cells
      that accompanies leiomyoma formation are unknown, although steroid hormones and
      peptide growth factors have been implicated. We hypothesized that endothelin-1
      (ET-1) is a physiological regulator of tumor growth. DESIGN: In this study, we
      investigated the role of ET-1 on growth of human leiomyoma cells and its
      synergistic effect with growth factors, as well as the signaling pathway involved
      in this interaction. METHODS: Leiomyoma cell proliferation was assayed by
      [H]thymidine incorporation and cell number. Protein kinase C (PKC) isoforms were
      analyzed by Western blot using specific antibodies. RESULTS: ET-1 on its own was
      unable to stimulate DNA synthesis but potentiated the leiomyoma cell growth
      effects of basic fibroblast growth factor (bFGF), epidermal growth factor (EGF),
      IGF-I and IGF-II. The failure of a protein tyrosine kinase (PTK) inhibitor,
      tyrphostin 51, to affect the potentiating effect of ET-1, supports the hypothesis
      of non-involvement of PTK in this process. The inhibition of PKC by calphostin C
      or its down-regulation by phorbol 12,13-dibutyrate (PDB) eliminated the
      potentiating effect of ET-1, but did not block cell proliferation induced by the
      growth factors alone. Five PKC isoforms (alpha, beta1, epsilon, delta and zeta)
      were detected in leiomyoma cells, but only phorbol ester-sensitive PKC isoforms
      (PKCalpha, epsilon and delta) contribute to the potentiating effect of leiomyoma
      cell growth by ET-1. CONCLUSIONS: We have demonstrated that ET-1 potentiates
      leiomyoma cell proliferation to growth factors through a PKC-dependent pathway.
      These findings suggest a possible involvement of ET-1 in the pathogenesis of
      leiomyomas.

PMID- 11331223
TI  - 1,25-Dihydroxyvitamin D3 stimulates the production of insulin-like growth factor
      binding proteins-2, -3 and -4 in human bone marrow stromal cells.
AB  - BACKGROUND: 1,25-Dihydroxyvitamin D3 (calcitriol) inhibits proliferation and
      stimulates differentiation of multiple cell types, including osteoblasts. Human
      (h) bone marrow stromal cells (MSCs) are a homogenous non-hematopoietic
      population of cells present in the bone marrow and exhibit a less differentiated
      osteoblastic phenotype. The IGF system, including IGFs-I, and -II and IGF binding
      proteins (IGFBPs), plays an important role in osteoblast cell proliferation and
      differentiation. OBJECTIVE: To examine the pattern of expression of the IGF
      system in hMSCss and its regulation by calcitriol. METHODS AND RESULTS: hMSCs
      express mRNA of both IGFs-I, and -II and IGFBPs-1 to -6 as shown by RT-PCR and
      northern blot analysis. As assessed by western ligand blotting (WLB) and western
      immmunoblot analysis, hMSCs secrete 38-42 kDa IGFBP-3, 24-28 kDa IGFBP-4 and a 33
      kDa IGFBP-2. Calcitriol (dose range 10-10 mol/l) exerted no consistent dose
      dependent effects on either IGF-I or IGF-II mRNA levels. In contrast, calcitriol
      treatment increased steady-state mRNA levels of IGFBPs-2, -3 and -4, but had no
      effect on IGFBP-5 or -6. Similarly, calcitriol increased the secretion of IGFBPs
      2, -3 and -4 as determined by WLB. We found no detectable basal IGFBP-3 or IGFBP
      4 protease activities in the absence or presence of calcitriol treatment.
      CONCLUSIONS: Our results demonstrate that hMSCs expressed a distinct pattern of
      IGFs and IGFBPs that may be related to their stage of differentiation. The
      observed increase in production of IGFBPs-2, -3 and -4 by hMSCs upon treatment
      with calcitriol may be an important mechanism mediating the effects of calcitriol
      on MSC proliferation and differentiation.

PMID- 11331224
TI  - Targeted cytotoxic analogs of luteinizing hormone-releasing hormone: a reply.

PMID- 11331225
TI  - Infections of the nervous system.
AB  - This article surveys common causes and pathologic features of nervous system
      infections within the general population. Special consideration is given to
      infections in people with the HIV virus.

PMID- 11331226
TI  - Demyelinating diseases, leukodystrophies, and other myelin disorders.
AB  - Magnetic resonance (MR) imaging recently has become the most sensitive clinical
      test in the detection of white matter disorders, yet neuropathologic evaluation
      remains the most specific. This article describes the gross and microscopic
      pathology of various diseases primarily or selectively affecting white matter.
      The discussion should provide deeper insight into the nature of white matter
      disease and assist in the interpretation of CT and MR images. The subject of
      white matter damage caused secondarily by such entities as neoplasia, trauma,
      infarction, or neuronal degeneration is not included.

PMID- 11331227
TI  - Neurodegenerative diseases.
AB  - This article briefly discusses and illustrates the major important
      neurodegenerative diseases of adulthood and neurometabolic (neurodegenerative in
      a broader sense) diseases of childhood and their gross neuropathology.
      Macroscopic views of the brain including the cerebellum and the brain stem and
      the spinal cord are given by external inspection as well as gross sections after
      brain cutting. Histologic details and photographs are supplied to explain and
      corroborate certain gross findings. This article attempts to correlate nosologic
      and neuropathologic features as the basis for interpreting neuroimaging data.

PMID- 11331228
TI  - Congenital malformations of the nervous system: a neuropathologic perspective.
AB  - Neurologists and neuropathologists face new diagnostic challenges in the era of
      molecular genetics and should strive to integrate descriptive morphologic data
      with the emerging understanding of genetic programming of ontogenesis. This
      integration is of particular importance in defining and understanding
      malformations of the developing brain and spinal cord. Both medical specialists
      have much to contribute to the clinical neurobiology of the twenty-first century,
      but new tools and perspectives are required.

PMID- 11331229
TI  - Tumors and tumorlike lesions of the spine and spinal cord.
AB  - In this article, a variety of disorders that may occur in the spine and spinal
      cord and behave as space occupying lesions are presented. The lesions may be of
      various natures such as infectious, inflammatory, demyelinating, neoplastic, and
      vascular disorders. In addition, cystic lesions and diseases of the vertebral
      column that secondarily affect the spinal cord are also discussed. Although the
      various aspects of these disorders are reviewed, the emphasis is given on their
      morphologic presentation, which may help the understanding of their radiologic
      appearances.

PMID- 11331230
TI  - Magnetic resonance imaging of spinal cord vascular malformations with an emphasis
      on the cervical spine.
AB  - Spinal vascular malformations (AVMs) are rare but important causes of treatable
      myelopathies. Recent advances in the interventional neuroradiology and
      neurosurgical techniques have improved the delineation and classification of
      these heterogeneous lesions. Because MR imaging usually is the first screening
      test for patients with myelopathy, the neuroradiologist must have a high level of
      knowledge of the common imaging characteristics of these lesions. This article
      reviews MR angiographic literature about spinal AVMs, Type I-IV AVMs and cervical
      Type I AVMs, describes their pathophysiology and common imaging characteristics,
      and elaborates on differences in cervical location from more typical positions.

PMID- 11331231
TI  - Magnetic resonance neurography: magnetic resonance imaging of peripheral nerves.
AB  - With advances in modern MR imaging, direct MR visualization of many peripheral
      nerves is now possible. MR nerve imaging can detect and delineate the extent of
      neural tumors, demonstrate nerve continuity in cases of traumatic injury, and
      demonstrate abnormal enlargement and abnormal signal in diseased peripheral
      nerves. This ability to image peripheral nerves has the potential to dramatically
      change the diagnosis and treatment of peripheral nerve disease. This article
      describes the techniques for peripheral nerve imaging and provides a brief
      overview of a broad spectrum of peripheral nerve abnormalities.

PMID- 11331232
TI  - Bioinformatics needs to adopt statistical thinking.

PMID- 11331233
TI  - Comparison of genomic DNA sequences: solved and unsolved problems.
AB  - MOTIVATION: The DNA sequences of entire genomes are being determined at a rapid
      rate. Whereas initial genome sequencing efforts were for organisms chosen to be
      widely spaced in the tree of life, there is a growing emphasis on projects to
      sequence a species that is sufficiently similar to an already-sequenced species
      to allow direct comparison of those two DNA sequences. This and other changes in
      genome sequencing strategies have created a strong need for new methods to
      compare genomic sequences. RESULTS: We sketch the current state of software for
      comparing genomic DNA sequences and outline research directions that we believe
      are likely to result in important advances in practice.

PMID- 11331234
TI  - Analysis of temporal gene expression profiles: clustering by simulated annealing
      and determining the optimal number of clusters.
AB  - MOTIVATION: Cluster analysis of genome-wide expression data from DNA microarray
      hybridization studies has proved to be a useful tool for identifying biologically
      relevant groupings of genes and samples. In the present paper, we focus on
      several important issues related to clustering algorithms that have not yet been
      fully studied. RESULTS: We describe a simple and robust algorithm for the
      clustering of temporal gene expression profiles that is based on the simulated
      annealing procedure. In general, this algorithm guarantees to eventually find the
      globally optimal distribution of genes over clusters. We introduce an iterative
      scheme that serves to evaluate quantitatively the optimal number of clusters for
      each specific data set. The scheme is based on standard approaches used in
      regular statistical tests. The basic idea is to organize the search of the
      optimal number of clusters simultaneously with the optimization of the
      distribution of genes over clusters. The efficiency of the proposed algorithm has
      been evaluated by means of a reverse engineering experiment, that is, a situation
      in which the correct distribution of genes over clusters is known a priori. The
      employment of this statistically rigorous test has shown that our algorithm
      places greater than 90% genes into correct clusters. Finally, the algorithm has
      been tested on real gene expression data (expression changes during yeast cell
      cycle) for which the fundamental patterns of gene expression and the assignment
      of genes to clusters are well understood from numerous previous studies.

PMID- 11331235
TI  - Retrieval and on-the-fly alignment of sequence fragments from the HIV database.
AB  - MOTIVATION: The amount of HIV-1 sequence data generated (presently around 42000
      sequences, of which more than 22000 are from the V3 region of the viral envelope)
      presents a challenge for anyone working on the analysis of these data. A major
      problem is obtaining the region of interest from the stored sequences, which
      often contain but are not limited to that region. In addition, multiple alignment
      programs generally cannot deal with the large numbers of sequences that are
      available for many HIV-1 regions. We set out to provide our users with a tool
      that will retrieve and create an initial alignment of the HIV sequences that are
      available for a given genomic region. RESULTS: The MPAlign (Multiple Pairwise
      Alignment) web interface is a collection of Perl scripts that retrieves sequences
      from the Los Alamos HIV sequence database based on a number of search parameters.
      All sequences were pairwise-aligned to a model sequence using the Hidden Markov
      Model-based program HMMER. The HMMER model is general enough to accommodate
      virtually all HIV-1 sequences stored in the database. To create a multiple
      sequence alignment, gaps were inserted into the sequences during retrieval, so
      that they are aligned to one another. Retrieving and aligning the almost 560
      gp120 sequences (approximately>1500 nt) stored in the database is at least 1500
      times faster than a similar Clustal alignment.

PMID- 11331236
TI  - Efficient large-scale sequence comparison by locality-sensitive hashing.
AB  - MOTIVATION: Comparison of multimegabase genomic DNA sequences is a popular
      technique for finding and annotating conserved genome features. Performing such
      comparisons entails finding many short local alignments between sequences up to
      tens of megabases in length. To process such long sequences efficiently, existing
      algorithms find alignments by expanding around short runs of matching bases with
      no substitutions or other differences. Unfortunately, exact matches that are
      short enough to occur often in significant alignments also occur frequently by
      chance in the background sequence. Thus, these algorithms must trade off between
      efficiency and sensitivity to features without long exact matches. RESULTS: We
      introduce a new algorithm, LSH-ALL-PAIRS, to find ungapped local alignments in
      genomic sequence with up to a specified fraction of substitutions. The length and
      substitution rate of these alignments can be chosen so that they appear
      frequently in significant similarities yet still remain rare in the background
      sequence. The algorithm finds ungapped alignments efficiently using a randomized
      search technique, locality-sensitive hashing. We have found LSH-ALL-PAIRS to be
      both efficient and sensitive for finding local similarities with as little as 63%
      identity in mammalian genomic sequences up to tens of megabases in length

PMID- 11331237
TI  - Analysis of genomic sequences by Chaos Game Representation.
AB  - MOTIVATION: Chaos Game Representation (CGR) is an iterative mapping technique
      that processes sequences of units, such as nucleotides in a DNA sequence or amino
      acids in a protein, in order to find the coordinates for their position in a
      continuous space. This distribution of positions has two properties: it is
      unique, and the source sequence can be recovered from the coordinates such that
      distance between positions measures similarity between the corresponding
      sequences. The possibility of using the latter property to identify succession
      schemes have been entirely overlooked in previous studies which raises the
      possibility that CGR may be upgraded from a mere representation technique to a
      sequence modeling tool. RESULTS: The distribution of positions in the CGR plane
      were shown to be a generalization of Markov chain probability tables that
      accommodates non-integer orders. Therefore, Markov models are particular cases of
      CGR models rather than the reverse, as currently accepted. In addition, the CGR
      generalization has both practical (computational efficiency) and fundamental
      (scale independence) advantages. These results are illustrated by using
      Escherichia coli K-12 as a test data-set, in particular, the genes thrA, thrB and
      thrC of the threonine operon.

PMID- 11331238
TI  - Unsupervised classification of noisy chromosomes.
AB  - MOTIVATION: Almost all methods of chromosome recognition assume supervised
      training; i.e. we are given correctly classified chromosomes to start the
      training phase. Noise, if any, is confined only in the representation of the
      chromosomes and not in the classification of the chromosomes. During the
      recognition phase, the problem is simply to calculate the string edit distance of
      the unknowns to the representatives chosen from the training phase and classify
      the unknowns accordingly. RESULTS: In this paper, a general method to tackle the
      difficult unsupervised induction problem is described. The success of the method
      is demonstrated by showing how the inductive agent learns weights in a dynamic
      manner that allows it to distinguish between noisy median and telocentric
      chromosomes without knowing their proper labels. The process of learning is
      characterized as the process of finding the right distance function, i.e. the
      distance function that can nicely separate the classes.

PMID- 11331239
TI  - The utility of different representations of protein sequence for predicting
      functional class.
AB  - MOTIVATION: Data Mining Prediction (DMP) is a novel approach to predicting
      protein functional class from sequence. DMP works even in the absence of a
      homologous protein of known function. We investigate the utility of different
      ways of representing protein sequence in DMP (residue frequencies, phylogeny,
      predicted structure) using the Escherichia coli genome as a model. RESULTS: Using
      the different representations DMP learnt prediction rules that were more accurate
      than default at every level of function using every type of representation. The
      most effective way to represent sequence was using phylogeny (75% accuracy and
      13% coverage of unassigned ORFs at the most general level of function: 69%
      accuracy and 7% coverage at the most detailed). We tested different methods for
      combining predictions from the different types of representation. These improved
      both the accuracy and coverage of predictions, e.g. 40% of all unassigned ORFs
      could be predicted at an estimated accuracy of 60% and 5% of unassigned ORFs
      could be predicted at an estimated accuracy of 86%.

PMID- 11331240
TI  - Predicting protein--protein interactions from primary structure.
AB  - MOTIVATION: An ambitious goal of proteomics is to elucidate the structure,
      interactions and functions of all proteins within cells and organisms. The
      expectation is that this will provide a fuller appreciation of cellular processes
      and networks at the protein level, ultimately leading to a better understanding
      of disease mechanisms and suggesting new means for intervention. This paper
      addresses the question: can protein-protein interactions be predicted directly
      from primary structure and associated data? Using a diverse database of known
      protein interactions, a Support Vector Machine (SVM) learning system was trained
      to recognize and predict interactions based solely on primary structure and
      associated physicochemical properties. RESULTS: Inductive accuracy of the trained
      system, defined here as the percentage of correct protein interaction predictions
      for previously unseen test sets, averaged 80% for the ensemble of statistical
      experiments. Future proteomics studies may benefit from this research by
      proceeding directly from the automated identification of a cell's gene products
      to prediction of protein interaction pairs.

PMID- 11331241
TI  - A graph layout algorithm for drawing metabolic pathways.
AB  - MOTIVATION: A large amount of data on metabolic pathways is available in
      databases. The ability to visualise the complex data dynamically would be useful
      for building more powerful research tools to access the databases. Metabolic
      pathways are typically modelled as graphs in which nodes represent chemical
      compounds, and edges represent chemical reactions between compounds. Thus, the
      problem of visualising pathways can be formulated as a graph layout problem.
      Currently available visual interfaces to biochemical databases either use static
      images or cannot cope well with more complex, non-standard pathways. RESULTS:
      This paper presents a new algorithm for drawing pathways which uses a combination
      of circular, hierarchic and force-directed graph layout algorithms to compute
      positions of the graph elements representing main compounds and reactions. The
      algorithm is particularly designed for cyclic or partially cyclic pathways or for
      combinations of complex pathways. It has been tested on five sample pathways with
      promising results.

PMID- 11331242
TI  - BioMolQuest: integrated database-based retrieval of protein structural and
      functional information.
AB  - MOTIVATION: Information about a particular protein or protein family is usually
      distributed among multiple databases and often in more than one entry in each
      database. Retrieval and organization of this information can be a laborious task.
      This task is complicated even further by the existence of alternative terms for
      the same concept. RESULTS: The PDB, SWISS-PROT, ENZYME, and CATH databases have
      been imported into a combined relational database, BIOMOLQUEST: A powerful search
      engine has been built using this database as a back end. The search engine
      achieves significant improvements in query performance by automatically utilizing
      cross-references between the legacy databases. The results of the queries are
      presented in an organized, hierarchical way.

PMID- 11331243
TI  - MAC5: Bayesian inference of phylogenetic trees from DNA sequences incorporating
      gaps.
AB  - SUMMARY: MAC5 implements MCMC sampling of the posterior distribution of tree
      topologies from DNA sequences containing gaps by using a five state model of
      evolution (the four nucleotides and the gap character).

PMID- 11331244
TI  - Cladogramer: incorporating haplotype frequency into cladogram analysis.
AB  - SUMMARY: We implement a program that incorporates polymorphic sites data,
      haplotype frequency arrays, and other factors, into cladogram estimation.

PMID- 11331245
TI  - A-Cell: graphical user interface for the construction of biochemical reaction
      models.
AB  - SUMMARY: A-Cell is a tool for constructing models of complex and complicated
      biochemical reactions. An important feature of A-Cell is its graphical user
      interface for constructing biochemical reactions. In addition, it has a
      capability of importing previously constructed models, combining them, and
      constructing a comprehensive model. The simulation program for the model is
      automatically generated by A-cell.

PMID- 11331246
TI  - Control of p53 ubiquitination and nuclear export by MDM2 and ARF.
AB  - p53 and ARF-INK4a are the two most frequently altered loci in human tumors. The
      activity of p53 protein is inhibited during normal cell growth by the proto
      oncoprotein MDM2 through either repression of p53-mediated transcription in the
      nucleus or proteasomal degradation of p53 protein in the cytoplasm. Responding to
      oncogenic signal-activated cell hyperproliferation, ARF-mediated antagonism of
      MDM2 inhibition results in p53 becoming active and its protein levels rising. The
      biochemical mechanisms of ubiquitination and nuclear export that underlie the
      functions of ARF and MDM2 in p53 control continue to emerge.

PMID- 11331247
TI  - Novel tumor-promoting property of tamoxifen.
AB  - The tumor-promoting phorbol ester TPA (12-O-tetradecanoylphorbol-13-acetate)
      cooperates with c-Src overexpression to transform rat fibroblasts. TPA transforms
      c-Src-overexpressing cells by depleting the delta isoform of protein kinase C
      (PKCdelta). Tamoxifen, which has both estrogen-mimetic and estrogen-antagonist
      properties, has been widely used to improve the prognosis of breast cancer
      patients. However, with extended use, there is an increased risk for endometrial
      and other cancers that can be observed within 10 years of treatment. We report
      here that tamoxifen, similar to TPA, cooperates with c-Src overexpression to
      transform 3Y1 rat fibroblasts. Tamoxifen induced both DNA synthesis and anchorage
      independent cell proliferation in c-Src-overexpressing, but not in parental, 3Y1
      rat fibroblasts. Tamoxifen also induced an association between c-Src and PKCdelta
      that resulted in the tyrosine phosphorylation and down-regulation of PKCdelta.
      These phenotypes were not induced by estrogen, indicating that the effect of
      tamoxifen was in addition to any estrogen-mimetic effects. Thus, in addition to
      the hyperplasia-inducing capability of an estrogen-mimetic, tamoxifen has an
      additional tumor-promoting capability similar to that of TPA. The dual tumor
      promoting capability of both estrogen- and TPA-mimetic properties for tamoxifen
      may contribute to the increased incidence of endometrial cancers observed in the
      relatively short exposure period of <10 years.

PMID- 11331248
TI  - Requirement of tyrosine-phosphorylated Vav for morphological differentiation of
      all-trans-retinoic acid-treated HL-60 cells.
AB  - Our previous data demonstrated that cellular and nuclear tyrosine-phosphorylated
      Vav associate with phosphoinositide 3-kinase during all-trans-retinoic acid
      dependent granulocytic differentiation of HL-60 cells. In this study, aimed to
      analyze the mechanism by which Vav is recruited and activated, we report that the
      Src homology 2 domain of Vav interacts with tyrosine-phosphorylated proteins in a
      differentiation-dependent manner. Two adaptor proteins, Cbl and SLP-76, were
      identified, showing a discrete distribution inside the cells, with Cbl absent
      from the nuclei and SLP-76 particularly abundant in the nuclear compartment. Of
      note, Vav interacts with the tyrosine kinase Syk, which is also present in the
      nuclear compartment and may phosphorylate Vav in vitro when cells differentiate.
      Inhibition of Syk activity by piceatannol prevents both in vitro and in vivo Vav
      tyrosine phosphorylation, its association with the regulatory subunit of
      phosphoinositide 3-kinase, and the nuclear modifications typically observed
      during granulocytic differentiation of this cell line. These findings suggest
      that tyrosine-phosphorylated Vav and its association with phosphoinositide 3
      kinase play a crucial role in all-trans-retinoic acid-induced reorganization of
      the nucleoskeleton, which is responsible for the changes in nuclear morphology
      observed during granulocytic differentiation of HL-60 cells.

PMID- 11331249
TI  - Human RERE is localized to nuclear promyelocytic leukemia oncogenic domains and
      enhances apoptosis.
AB  - RE repeats encoded (RERE) was identified recently as a protein with high homology
      to the atrophin-1 protein, which appears to be causal in the hereditary
      neurodegenerative disorder termed dentatorubral-pallidoluysian atrophy (DRPLA)
      caused by an abnormal glutamine expansion. We have independently identified RERE
      in a search for genes localized to the translocation breakpoint region at
      chromosome 1p36.2 in the neuroblastoma cell line NGP. Here we show that
      neuroblastoma tumor cell lines display reduced abundance of RERE transcripts.
      Furthermore, we detected RERE protein mainly in the nucleus, where it colocalizes
      with the promyelocytic leukemia protein in promyelocytic leukemia oncogenic
      domains (PODs). Overexpression of RERE recruits a fraction of the proapoptotic
      protein BAX to PODS: This observation correlates with RERE-induced apoptosis,
      which occurs in a caspase-dependent manner. These results identify RERE as a
      novel component of PODs and suggest an important role of RERE in the control of
      cell survival.

PMID- 11331251
TI  - Impact of peri-stent remodeling on restenosis: a volumetric intravascular
      ultrasound study.
AB  - BACKGROUND: Vessel remodeling is an important mechanism of late lumen loss after
      nonstent coronary interventions. However, its impact on in-stent restenosis has
      not been systematically investigated. METHODS AND RESULTS: Serial volumetric
      intravascular ultrasound analyses (poststent and follow-up) were performed in 55
      lesions treated with a balloon-expandable stent (ACS MultiLink) using standard
      stent deployment techniques. The vessel volume (VV), lumen volume (LV), and
      volume bordered by the stent (SV) were measured using Simpson's method. The
      volume of plaque and neointima outside the stent (peri-stent volume, PSV) and
      volume of neointima within the stent (intrastent volume) were also measured. The
      change of each parameter during the follow-up period (follow-up minus poststent)
      was calculated and then divided by SV to normalize these values (designated as
      percent change [%]). As expected, %PSV directly correlated with %VV (P<0.0001,
      r=0.935), with no significant SV. A highly significant inverse correlation was
      seen between %PSV and the percent change of intrastent volume (P<0.0001,
      r=0.517). Consequently, %LV significantly correlated with peri-stent remodeling,
      as measured by %VV (P<0.0001, r=0.602). CONCLUSION: Positive remodeling of the
      vessel exterior to a coronary stent occurs to a variable degree after stent
      implantation. There is a distinct trade-off between positive remodeling and in
      stent hyperplasia: in segments in which the degree of peri-stent remodeling is
      less, intrastent neointimal proliferation is greater and accompanied by more
      significant late lumen loss.

PMID- 11331250
TI  - Beta-chemokine induction of activation protein-1 and cyclic AMP responsive
      element activation in human myeloid cells.
AB  - Chemokines effect leukocyte chemotaxis and activation through their binding to
      specific G protein-coupled receptors. Although early steps in chemokine signal
      transduction pathways have been characterized, there is relatively limited
      information available at the transcription factor level. To that end, we have
      examined the binding activity on activation protein-1 (AP-1) and cyclic AMP
      responsive element (CRE) target sequences in human THP-1 myeloid cells after
      treatment with the beta-chemokine macrophage inflammatory protein (MIP-1alpha).
      MIP-1alpha induced both AP-1 and CRE activation. Although inhibition of protein
      kinase C blocked the AP-1 activity induced by this chemokine, there was no
      decrease in CRE activation in the presence of a protein kinase A inhibitor. Using
      kinase assays, it appeared that mitogen-activated protein kinase pathways were
      involved in CRE activation. In addition, HIV-1 infection of THP-1 cells resulted
      in constitutive activation of AP-1 and CRE elements but no further response to
      MIP-1alpha treatment. These results suggest that beta-chemokines act via protein
      kinase C-dependent pathways and mitogen-activated protein kinase pathways to
      modulate the host transcriptional response in myeloid cells, and that this
      response is altered by HIV infection.

PMID- 11331252
TI  - Sex differences in neurological outcomes and mortality after cardiac surgery: a
      society of thoracic surgery national database report.
AB  - BACKGROUND: The purpose of this study was to evaluate whether women undergoing
      cardiac surgery are more likely to suffer neurological complications than men and
      whether these complications could explain, at least in part, their higher
      perioperative mortality. METHODS AND RESULTS: The Society of Thoracic Surgery
      National Cardiac Surgery Database was examined for the years 1996 and 1997 to
      determine the frequency of new neurological events (stroke, transient ischemic
      attack, or coma) occurring after cardiac surgery. We reviewed clinical
      information on 416 347 patients (32% women) for whom complete neurological
      outcome data were available. New neurological events after surgery were higher
      for women than for men (3.8% versus 2.4%, P=0.001). For the whole group, the 30
      day mortality was higher for women than for men (5.7% versus 3.5%, P=0.001), and
      among those patients who suffered a perioperative neurological event, mortality
      was also significantly higher for women than men (32% versus 28%, P=0.001). After
      adjustment for other risk factors (eg, age, history of hypertension and/or
      diabetes, duration of cardiopulmonary bypass, and other comorbid conditions) by
      multivariable logistic regression, female sex was independently associated with
      significantly higher risk of suffering new neurological events after cardiac
      surgery (OR 1.21, 95% CI 1.14 to 1.28, P=0.001). CONCLUSIONS: Women undergoing
      cardiac surgery are more likely than men to suffer new perioperative neurological
      events, and they have higher 30-day mortality when these complications occur. The
      higher incidence of perioperative neurological complications in women cannot be
      explained by currently known risk factors.

PMID- 11331253
TI  - Randomized, single-blind, placebo-controlled pilot study of catheter-based
      myocardial gene transfer for therapeutic angiogenesis using left ventricular
      electromechanical mapping in patients with chronic myocardial ischemia.
AB  - BACKGROUND: Catheter-based myocardial gene transfer (GTx) has not been previously
      tested in human subjects. Accordingly, we performed a pilot study to investigate
      the feasibility and safety of catheter-based myocardial GTx of naked plasmid DNA
      encoding vascular endothelial growth factor-2 (phVEGF-2) in patients with chronic
      myocardial ischemia. METHODS AND RESULTS: A steerable, deflectable 8F catheter
      incorporating a 27-guage needle was advanced percutaneously to the left
      ventricular myocardium of 6 patients with chronic myocardial ischemia. Patients
      were randomized (1:1) to receive phVEGF-2 (total dose, 200 microgram), which was
      administered as 6 injections into ischemic myocardium (total, 6.0 mL), or placebo
      (mock procedure). Injections were guided by NOGA left ventricular
      electromechanical mapping. Patients initially randomized to placebo became
      eligible for phVEGF-2 GTx if they had no clinical improvement 90 days after their
      initial procedure. Catheter injections (n=36) caused no changes in heart rate or
      blood pressure. No sustained ventricular arrhythmias, ECG evidence of infarction,
      or ventricular perforations were observed. phVEGF-2-transfected patients
      experienced reduced angina (before versus after GTx, 36.2+/-2.3 versus 3.5+/-1.2
      episodes/week) and reduced nitroglycerin consumption (33.8+/-2.3 versus 4.1+/-1.5
      tablets/week) for up to 360 days after GTx; reduced ischemia by electromechanical
      mapping (mean area of ischemia, 10.2+/-3.5 versus 2.8+/-1.6 cm(2), P=0.04); and
      improved myocardial perfusion by SPECT-sestamibi scanning for up to 90 days after
      GTx when compared with images obtained after control procedure. Conclusions-This
      randomized trial of catheter-based phVEGF-2 myocardial GTx provides preliminary
      indications regarding the feasibility, safety, and potential efficacy of
      percutaneous myocardial GTx to human left ventricular myocardium.

PMID- 11331254
TI  - Metabolic abnormalities characteristic of dysmetabolic syndrome predict the
      development of transplant coronary artery disease: a prospective study.
AB  - BACKGROUND: This study examines the hypothesis that metabolic abnormalities of
      dysmetabolic syndrome are risk factors for transplant coronary artery disease
      (TxCAD). METHODS AND RESULTS: Sixty-six patients without overt diabetes, 2 to 4
      years after surgery, underwent intracoronary ultrasound (ICUS), measurement of
      plasma glucose and insulin after oral glucose (75 g), and fasting lipid and
      lipoproteins. TxCAD incidence by angiography or autopsy was prospectively
      determined during subsequent follow-up (8 years). Coronary artery intimal
      thickness (IT) and subsequent outcomes were compared in patients stratified as
      having "high" versus "low" plasma glucose (>8.9 mmol/L) and insulin (>760 pmol/L)
      2 hours after glucose challenge; and "abnormal" versus "normal" fasting lipid and
      lipoprotein concentrations as defined by the National Cholesterol Education
      PROGRAM: Patients with high glucose or insulin concentrations had greater IT:
      0.38+/-0.05 versus 0.22+/-0.02 mm, P</=0.05, and 0.39+/-0.05 versus 0.20+/-0.02
      mm, P</=0.01, respectively. Freedom from TxCAD was 56+/-11% versus 81+/-6%
      (P<0.01) in patients with high versus low glucose and 57+/-10% versus 82+/-7%
      (P<0.05) in patients with high versus low insulin. Actuarial survival was 60+/
      12% versus 92+/-5% (P<0.005) in patients with high versus low glucose and 72+/-9%
      versus 88+/-6% (P<0.05) in patients with high versus low insulin. Triglycerides
      and VLDL were higher and HDL was lower in patients with IT >0.3 mm than with IT
      </=0.3 mm. TxCAD incidence was higher in patients with high plasma TG and VLDL
      and low HDL. CONCLUSIONS: These data suggest that insulin resistance plays a role
      in TXCAD:

PMID- 11331255
TI  - Respiratory muscle dysfunction in congestive heart failure: clinical correlation
      and prognostic significance.
AB  - BACKGROUND: In congestive heart failure (CHF), the prognostic significance of
      impaired respiratory muscle strength has not been established. METHODS AND
      RESULTS: Maximal inspiratory pressure (Pi(max)) was prospectively determined in
      244 consecutive patients (207 men) with CHF (ischemic, n=75; idiopathic dilated
      cardiomyopathy, n=169; age, 54+/-11 years; left ventricular ejection fraction
      [LVEF], 22+/-10%). Pi(max) was lower in the 244 patients with CHF than in 25
      control subjects (7.6+/-3.3 versus 10.5+/-3.7 kPa; P=0.001). The 57 patients
      (23%) who died during follow-up (23+/-16 months; range, 1 to 48 months) had an
      even more reduced Pi(max) (6.3+/-3.2 versus 8.1+/-3.2 kPa in survivors; P=0.001).
      Kaplan-Meier survival curves differentiated between patients subdivided according
      to quartiles for Pi(max) (P=0.014). Pi(max) was a strong risk predictor in both
      univariate (P=0.001) and multivariate Cox proportional hazard analyses (P=0.03);
      multivariate analyses also included NYHA functional class, LVEF, peak oxygen
      consumption (peak VO(2)), and norepinephrine plasma concentration. The areas
      under the receiver-operating characteristic curves for prediction of 1-year
      survival were comparable for Pi(max) and peak VO(2) (area under the curve [AUC],
      0.68 versus 0.73; P=0.28), and they improved with the triple combination of
      Pi(max), peak VO(2), and LVEF (AUC, 0.82; P=0.004 compared with AUC of Pi(max)).
      CONCLUSIONS: In patients with CHF, inspiratory muscle strength is reduced and
      emerges as a novel, independent predictor of prognosis. Because testing for
      Pi(max) is simple in clinical practice, it might serve as an additional factor to
      improve risk stratification and patient selection for cardiac transplantation.

PMID- 11331256
TI  - Implantation of cardioverter defibrillators without induction of ventricular
      fibrillation.
AB  - BACKGROUND: The upper limit of vulnerability (ULV) is the weakest shock at which
      ventricular fibrillation (VF) is not induced by a T-wave shock. This study tested
      the hypothesis that a vulnerability safety margin based on the ULV can be used as
      an implantable cardioverter-defibrillator implantation criterion. METHODS AND
      RESULTS: Implantable cardioverter-defibrillators were implanted in 80 patients if
      T-wave shocks did not induce VF and the baseline-rhythm R wave was >/=7 mV. The T
      wave shock was 10 J in the first 45 patients (group A) and 15 J in the last 35
      patients (group B). After inductionless implantations, the first VF shock was
      programmed to the T-wave shock plus 5 J. If T-wave shocks induced VF, the ULV was
      measured and the first shock was programmed to the ULV+5 J. Inductionless
      implantations were performed in 58 patients (72%), 28 in group A (62%) and 30 in
      group B (86%; P=0.04). If T-wave scanning had been done at 15 J in group A
      patients, inductionless implantations could have been performed in 84% of them.
      At 3 months, VF was induced twice during electrophysiological study in 75
      patients (94%). All VFs were detected in </=4.7 s and were terminated by the
      first shock. During follow-up, 197 of 198 appropriate first shocks for rapid
      ventricular tachycardia or VF (99%) were successful in patients who had
      inductionless implantations (95% confidence intervals, 97% to 100%). CONCLUSION:
      Inductionless implantations can be performed in >80% of implantable cardioverter
      defibrillator recipients using a vulnerability safety margin based on a T-wave
      scan at 15.

PMID- 11331257
TI  - Balloon dilation angioplasty of peripheral pulmonary stenosis associated with
      Williams syndrome.
AB  - BACKGROUND: Experience of balloon dilation of peripheral pulmonary stenosis (PPS)
      in Williams syndrome (WS) is limited. METHODS AND RESULTS: Catheterizations in
      all patients with WS undergoing therapy for PPS from 1984 to 1999 were reviewed.
      Criteria for successful dilation included an increase >50% in predilation
      diameter and a decrease >20% in ratio of right ventricular (RV) to aortic (Ao)
      systolic pressure. Median age and weight were 1.5 years and 9.5 kg. There were
      134 dilations during 39 procedures in 25 patients. The success rate for initial
      dilations was 51%. In multivariate analysis, successful dilation was more likely
      (1) in distal than in central pulmonary arteries (P=0.02), (2) if the balloon
      waist resolved with inflation (P=0.001), and (3) with larger balloon/stenosis
      ratio (P<0.001). RV pressure was unchanged after dilation (96+/-30 versus 97+/-31
      mm Hg), primarily because of failure to enlarge central pulmonary arteries. The
      Ao pressure increased (102+/-14 versus 109+/-19 mm Hg, P=0.03), and the RV/Ao
      pressure ratio decreased (0.97+/-0.34 versus 0.91+/-0.30, P=0.05). Aneurysms
      developed after 24 dilations (18%) and were not related to balloon/stenosis
      ratio. Balloon rupture in 12 dilations produced an aneurysm in all 7 cases when
      rupture was in a hypoplastic segment. Three patients died, none from pulmonary
      artery trauma, and all before 1994. CONCLUSIONS: Mortality occurred early in our
      experience. Despite successful dilation of distal pulmonary arteries, there was
      modest initial hemodynamic improvement, mainly because of persistent central
      pulmonary artery obstruction. A serial approach of distal dilations followed by
      surgical repair of proximal obstruction may be a rational and successful therapy.

PMID- 11331258
TI  - Echolucent plaques are associated with high risk of ischemic cerebrovascular
      events in carotid stenosis: the tromso study.
AB  - BACKGROUND: The purpose of the study was to assess in a prospective design
      whether plaque morphology is associated with risk of ischemic stroke and other
      cerebrovascular events in subjects with carotid stenosis. METHODS AND RESULTS: A
      total of 223 subjects with carotid stenosis (123 with 35% to 49% degree of
      stenosis, 100 with 50% to 99% stenosis) and 215 control subjects matched by age
      and sex who participated in a population health survey at baseline were followed
      up for 3 years. Plaque echogenicity was assessed by ultrasound at baseline and
      scored as echolucent, predominantly echolucent, predominantly echogenic, or
      echogenic. Forty-four subjects experienced >/=1 ischemic cerebrovascular events
      in the follow-up period. Plaque echogenicity, degree of stenosis, and white blood
      cell count were independent predictors of cerebrovascular events. The unadjusted
      relative risk for cerebrovascular events was 13.0 (95% CI 4.5 to 37.4) in
      subjects with echolucent plaques and 3.7 (95% CI 0.7 to 18.2) in subjects with
      echogenic plaques when subjects without stenosis were used as the reference. The
      adjusted relative risk for cerebrovascular events in subjects with echolucent
      plaques was 4.6 (95% CI 1.1 to 18.9), and there was a significant linear trend
      (P=0.015) for higher risk with increasing plaque echolucency. The adjusted
      relative risk for a 10% increase in the degree of stenosis was 1.2 (95% CI 1.04
      to 1.4). CONCLUSIONS: Subjects with echolucent atherosclerotic plaques have
      increased risk of ischemic cerebrovascular events independent of degree of
      stenosis and cardiovascular risk factors. Subjects at high risk for ischemic
      vascular events may be identified by ultrasound assessment of plaque morphology.

PMID- 11331259
TI  - Bidirectional Glenn procedure improves the mechanical efficiency of a total
      cavopulmonary connection in high-risk fontan candidates.
AB  - BACKGROUND: A total cavopulmonary connection (TCPC) is a widely performed
      surgical procedure for Fontan candidates. High-risk candidates who have undergone
      the bidirectional Glenn procedure (BDG) before TCPC have shown good results. The
      exact mechanism of this procedure, however, is still poorly understood. We
      hypothesized that a volume reduction with BDG improved ventricular contractility,
      thereby optimizing mechanical efficiency after TCPC. METHODS AND RESULTS: We
      measured percent normal systemic ventricular end-diastolic volume (%N-EDV),
      contractility (end-systolic elastance; E(es)), afterload (effective arterial
      elastance; E(a)), and mechanical efficiency (ventriculoarterial coupling;
      E(a)/E(es)) on the basis of the cardiac catheterization data before and after
      TCPC. Eighteen patients who underwent staged TCPC after BDG (staged group) were
      compared with 29 patients who underwent primary TCPC (primary group). E(es) and
      E(a) were approximated as follows: E(es)=mean arterial pressure/minimal
      ventricular volume, and E(a)=maximal ventricular pressure/(maximal ventricular
      volume-minimal ventricular volume), and E(a)/E(es) was then calculated. The
      ventricular volume was normalized with the body surface area. A canine
      experimental model with conductance catheter was used to validate the accuracy of
      this approximation of E(es) and E(a). %N-EDV decreased after TCPC in both groups.
      In the staged group, a smaller ventricular volume resulted in better
      contractility (E(es)). Although afterload (E(a)) increased in both groups, the
      increment of E(a) was smaller in the staged group. These changes resulted in an
      improvement of E(a)/E(es) in the staged group, whereas E(a)/E(es) increased in
      the primary group. CONCLUSIONS: The volume reduction of BDG preceding TCPC allows
      for any afterload mismatch to be corrected, thereby improving ventricular
      energetics after TCPC.

PMID- 11331260
TI  - Matrix-dependent mechanism of neutrophil-mediated release and activation of
      matrix metalloproteinase 9 in myocardial ischemia/reperfusion.
AB  - BACKGROUND: A key component of reperfusion of myocardial infarction is an
      immediate inflammatory response, which enhances tissue repair. Matrix turnover is
      crucial to tissue repair, and matrix metalloproteinases (MMPs) are key enzymes
      involved in matrix degradation. The hypothesis tested is that one inflammation
      based effector of tissue repair is the secretion and activation of MMP-9 by
      infiltrating neutrophils. METHODS AND RESULTS: Cardiac lymph and tissue were
      assayed for atent and active MMP-2 and MMP-9 by zymography and immunochemistry.
      Dual-labeling immunofluorescence determined the cellular source of MMP-9 protein.
      Isolated canine neutrophils were incubated with preischemic and postischemic
      cardiac lymph in the presence and absence of collagen-fibronectin pads, and the
      supernatants were assayed for latent and active MMP-9. MMP-9 increased during the
      first hours of reperfusion in both lymph supernatants and myocardial extracts,
      and this increase was of neutrophil origin. MMP-9 in the cardiac lymph remained
      latent but was activatable. In contrast, MMP-9 in the myocardium was in both
      latent and active forms. In situ zymography demonstrated that activated MMP-9
      surrounded the infiltrated neutrophils. When postischemic cardiac lymph was
      incubated with neutrophils in vitro, MMP-9 secretion and activation occurred only
      in the presence of a collagen-fibronectin substrate; preischemic cardiac lymph
      did not induce significant secretion or activation. CONCLUSIONS: Infiltrating
      neutrophils are an early source of MMP-9 after reperfusion, and a portion of MMP
      9 in the myocardium is active. Infiltrating neutrophils may localize MMP-9
      activation by secreting MMP-9 and as a source of activating proteases.

PMID- 11331261
TI  - Effects of in vivo nitroglycerin treatment on activity and expression of the
      guanylyl cyclase and cGMP-dependent protein kinase and their downstream target
      vasodilator-stimulated phosphoprotein in aorta.
AB  - BACKGROUND: Chronic in vivo treatment with nitroglycerin (NTG) induces tolerance
      to nitrates and cross-tolerance to nitrovasodilators and endothelium-derived
      nitric oxide (NO). We previously identified increased vascular superoxide
      formation and reduced NO bioavailability as one causal mechanism. It is still
      controversial whether intracellular downstream signaling to nitrovasodilator
      derived NO is affected as well. METHODS AND RESULTS: We therefore studied the
      effects of 3-day NTG treatment of rats and rabbits on activity and expression of
      the immediate NO target soluble guanylyl cyclase (sGC) and on the cGMP-activated
      protein kinase I (cGK-I). Tolerance was induced either by chronic NTG infusion
      via osmotic minipumps (rats) or by NTG patches (rabbits). Western blot analysis,
      semiquantitative reverse transcription-polymerase chain reaction, and Northern
      blot analysis revealed significant and comparable increases in the expression of
      sGC alpha(1) and beta(1) subunit protein and mRNA. Studies with the oxidative
      fluorescent dye hydroethidine revealed an increase in superoxide in the
      endothelium and smooth muscle. Stimulation with NADH increased superoxide signals
      in both layers. Although cGK-I expression in response to low-dose NTG was not
      changed, a strong reduction in vasodilator-stimulated phosphoprotein (VASP)
      serine239 phosphorylation (specific substrate of cGK-I) was observed in tolerant
      tissue from rats and rabbits. Concomitant in vivo and in vitro treatment with
      vitamin C improved tolerance, reduced oxidative stress, and improved P-VASP.
      CONCLUSIONS: We therefore conclude that increased expression of sGC in the
      setting of tolerance reflects a chronic inhibition rather than an induction of
      the sGC-cGK-I pathway and may be mediated at least in part by increased vascular
      superoxide.

PMID- 11331262
TI  - Beneficial effects on skeletal muscle of the angiotensin II type 1 receptor
      blocker irbesartan in experimental heart failure.
AB  - BACKGROUND: In congestive heart failure (CHF), skeletal muscle shows increased
      expression of fast myosin heavy chains (MHC) and fibers, muscle atrophy,
      increased fatigability, and decreased endurance. Atrophy is secondary to myocyte
      apoptosis, which is probably triggered by tumor necrosis factor-alpha (TNFalpha).
      Angiotensin II receptors are thought to play a role in controlling apoptosis. We
      tested the hypothesis that angiotensin II receptor blockade could prevent
      skeletal muscle apoptosis in rats with CHF. METHODS AND RESULTS: CHF was induced
      by injecting 36 rats with 30 mg/kg monocrotaline. Ten additional animals were
      injected with saline and acted as controls. After 2 weeks, 18 of the 36 rats with
      CHF were treated with 7 mg. kg(-1). d(-1) irbesartan through osmotic minipumps,
      and 10 of the 36 rats were treated with 2 mg. kg(-1). d(-1) nifedipine in
      drinking water. After 2 additional weeks, rats were killed. Tibialis anterior
      cross-sectional area, MHC composition, myocyte apoptosis, Bcl-2, pro-caspase 3,
      and activated caspases 3 and 9 were determined, as were plasma levels of TNFalpha
      and angiotensin II. Myocyte apoptosis and muscle atrophy were significantly
      decreased with irbesartan compared with untreated CHF rats. Irbesartan-treated
      rats had fewer cells labeled positively with terminal deoxynucleotidal
      transferase-mediated dUTP nick-end labeling and fewer caspases; however, they
      also had increased Bcl-2 levels and muscle fiber cross-sectional areas. The MHC
      pattern in irbesartan-treated animals was similar to that in controls. Nifedipine
      animals behaved like the untreated CHF animals. Angiotensin II was increased 3-
      to 4-fold in all CHF rats (treated and untreated). TNFalpha levels were decreased
      in irbesartan-treated rats but not in nifedipine-treated rats. CONCLUSIONS:
      Angiotensin II receptor blockade can protect from the development of apoptosis
      dependent atrophy and from changes in MHCS: The reduction of TNFalpha may play a
      role in this process.

PMID- 11331263
TI  - Increased myocardial GRP94 amounts during sustained atrial fibrillation: a
      protective response?
AB  - BACKGROUND: Structural and phenotypic changes of cardiomyocytes characterize
      atrial fibrillation. We investigated whether changes in the glucose-regulated
      protein GRP94, which is essential for cell viability, occur in the presence of
      chronic atrial fibrillation. METHODS AND RESULTS: Samples of fibrillating atrial
      myocardium obtained from both goat and human hearts were analyzed for GRP94
      expression by an immunologic approach. In goats, atrial fibrillation was induced
      and maintained for 2, 4, 8, and 16 weeks. After 16 weeks of atrial fibrillation,
      cardioversion was applied and followed by 8 weeks of sinus rhythm. GRP94 levels
      doubled in goat atrial myocytes after 4 to 16 weeks of fibrillation with respect
      to normal atria and returned to control levels in atrial myocardium of
      cardioverted goats. Immunohistochemical analyses confirm that GRP94 increase
      occurred within cardiomyocytes. Significantly, increased levels of GRP94 were
      also observed in samples from human fibrillating atria. In the absence of signs
      of myocyte irreversible damage, the GRP94 increase in fibrillating atria is
      comparable to GRP94 levels observed in perinatal goat myocardium. However,
      calreticulin, another endoplasmic reticulum protein highly expressed in perinatal
      hearts, does not increase in fibrillating atria, whereas inducible HSP70, a
      cytoplasm stress protein that is expressed in perinatal goat hearts at levels
      comparable to those observed in the adult heart, shows a significant increase in
      chronic fibrillating atria. CONCLUSIONS: Our data demonstrate a large, reversible
      increase in GRP94 in fibrillating atrial myocytes, which may be related to the
      appearance of a protective phenotype.

PMID- 11331264
TI  - Impact of sex and gonadal steroids on prolongation of ventricular repolarization
      and arrhythmias induced by I(K)-blocking drugs.
AB  - BACKGROUND: Mechanisms for longer rate-corrected QT intervals and higher
      incidences of drug-induced torsade de pointes in women than in men are
      incompletely defined, although gonadal steroids are assumed to be important
      determinants of these differences. METHODS AND RESULTS: We used microelectrode
      techniques to study isolated rabbit right ventricular endocardium from control
      male and female and castrated male (ORCH) and female (OVX) rabbits. Action
      potential duration to 30% repolarization (APD(30)) was significantly shorter in
      male than female and in ORCH than OVX at a cycle length of 500 ms. The I(Ks)
      blocker chromanol 293B had no effect on APD in males or females. The I(Kr)
      blocker dofetilide prolonged APD in female and ORCH more than in male and OVX. At
      10(-)(6) mol/L dofetilide (cycle length=1 second), the incidence of early
      afterdepolarizations was: female, 67%; ORCH, 56%; male, 40%; and OVX, 28%. Serum
      17beta-estradiol levels were unrelated to the effects of dofetilide, but as
      testosterone levels increased, the dofetilide effect to increase APD diminished,
      as did early afterdepolarization incidence. CONCLUSIONS: Sex-related differences
      in basal right ventricular endocardial AP configuration persist in castrated
      rabbits, suggesting that extragonadal factors contribute to the differences in
      ventricular repolarization. In this model, drugs that block I(Kr) but not I(Ks)
      prolong repolarization in a way that suggests that protection from excess
      prolongation in males is attributable to testosterone, whereas the risk of excess
      prolongation of repolarization in females is related to sex-determined factors in
      addition to estrogen.

PMID- 11331265
TI  - Low high-density lipoprotein cholesterol as a risk factor in coronary heart
      disease: a working group report.

PMID- 11331266
TI  - Edge stenosis after intracoronary radiotherapy: angiographic, intravascular, and
      histological findings.

PMID- 11331267
TI  - False aneurysms of an ascending-aorta-to-abdominal-aorta bypass for coarctation
      of the aorta.

PMID- 11331269
TI  - Cloning of a novel phosphatidylinositol kinase-related kinase: characterization
      of the human SMG-1 RNA surveillance protein.
AB  - We have cloned and characterized a new member of the phosphatidylinositol kinase
      (PIK)-related kinase family. This gene, which we term human SMG-1 (hSMG-1), is
      orthologous to Caenorhabditis elegans SMG-1, a protein that functions in nonsense
      mediated mRNA decay (NMD). cDNA sequencing revealed that hSMG-1 encodes a protein
      of 3031 amino acids containing a conserved kinase domain, a C-terminal domain
      unique to the PIK-related kinases and an FKBP12-rapamycin binding-like domain
      similar to that found in the PIK-related kinase mTOR. Immunopurified FLAG-tagged
      hSMG-1 exhibits protein kinase activity as measured by autophosphorylation and
      phosphorylation of the generic PIK-related kinase substrate PHAS-1. hSMG-1 kinase
      activity is inhibited by high nanomolar concentrations of wortmannin (IC(50) =
      105 nm) but is not inhibited by a FKBP12-rapamycin complex. Mutation of conserved
      residues within the kinase domain of hSMG-1 abolishes both autophosphorylation
      and substrate phosphorylation, demonstrating that hSMG-1 exhibits intrinsic
      protein kinase activity. hSMG-1 phosphorylates purified hUpf1 protein, a
      phosphoprotein that plays a critical role in NMD, at sites that are also
      phosphorylated in whole cells. Based on these data, we conclude that hSMG-1 is
      the human orthologue to C. elegans SMG-1. Our data indicate that hSMG-1 may
      function in NMD by directly phosphorylating hUpf1 protein at physiologically
      relevant sites.

PMID- 11331270
TI  - Cyclic AMP-independent activation of protein kinase A by vasoactive peptides.
AB  - Protein kinase A (PKA) is an important effector enzyme commonly activated by
      cAMP. The present study focuses on our finding that the vasoactive peptide
      endothelin-1 (ET1), whose signaling is not coupled to cAMP production, stimulates
      PKA in two independent cellular models. Using an in vivo assay for PKA activity,
      we found that ET1 stimulated PKA in HeLa cells overexpressing ET1 receptors and
      in aortic smooth muscle cells expressing endogenous levels of ET1 receptors. In
      these cell models, ET1 did not stimulate cAMP production, indicating a novel
      mechanism for PKA activation. The ET1-induced activation of PKA was found to be
      dependent on the degradation of inhibitor of kappaB, which was previously
      reported to bind and inhibit PKA. ET1 potently stimulated the nuclear factor
      kappaB pathway, and this effect was inhibited by overexpression of the inhibitor
      of kappaB dominant negative mutant (IkappaBalpham) and by treatment with the
      proteasome inhibitor MG-132. Importantly, IkappaBalpham and MG-132 had similar
      inhibitory effects on ET1-induced activation of PKA without affecting G(s)
      mediated activation of PKA or ET1-induced phosphorylation of mitogen-activated
      protein kinase. Finally, another vasoactive peptide, angiotensin II, also
      stimulated PKA in a cAMP-independent manner in aortic smooth muscle cells. These
      findings suggest that cAMP-independent activation of PKA might be a general
      response to vasoactive peptides.

PMID- 11331271
TI  - Ribosomal protein S5 interacts with the internal ribosomal entry site of
      hepatitis C virus.
AB  - Translational initiation of hepatitis C virus (HCV) genome RNA occurs via its
      highly structured 5' noncoding region called the internal ribosome entry site
      (IRES). Recent studies indicate that HCV IRES and 40 S ribosomal subunit form a
      stable binary complex that is believed to be important for the subsequent
      assembly of the 48 S initiation complex. Ribosomal protein (rp) S9 has been
      suggested as the prime candidate protein for binding of the HCV IRES to the 40 S
      subunit. RpS9 has a molecular mass of approximately 25 kDa in UV cross-linking
      experiments. In the present study, we examined the approximately 25-kDa proteins
      of the 40 S ribosome that form complexes with the HCV IRES upon UV cross-linking.
      Immunoprecipitation with specific antibodies against two 25-kDa 40 S proteins,
      rpS5 and rpS9, clearly identified rpS5 as the protein bound to the IRES. Thus,
      our results support rpS5 as the critical element in positioning the HCV RNA on
      the 40 S ribosomal subunit during translation initiation.

PMID- 11331272
TI  - Functional interplay between type I collagen and cell surface matrix
      metalloproteinase activity.
AB  - Type I collagen stimulation of pro-matrix metalloproteinase (pro-MMP)-2
      activation by ovarian cancer cells involves beta(1) integrin receptor clustering;
      however, the specific cellular and biochemical events that accompany MMP
      processing are not well characterized. Collagenolysis is not required for
      stimulation of pro-MMP-2 activation, and denatured collagen does not elicit an
      MMP-2 activation response. Similarly, DOV13 cells bind to intact collagen
      utilizing both alpha(2)beta(1) and alpha(3)beta(1) integrins but interact poorly
      with collagenase-treated or thermally denatured collagen. Antibody-induced
      clustering of alpha(3)beta(1) strongly promotes activation of pro-MMP-2, whereas
      alpha(2)beta(1) integrin clustering has only marginal effects. Membrane-type 1
      (MT1)-MMP is present on the DOV13 cell surface as both an active 55-kDa TIMP-2
      binding species and a stable catalytically inactive 43-kDa form. Integrin
      clustering stimulates cell surface expression of MT1-MMP and co-localization of
      the proteinase to aggregated integrin complexes. Furthermore, cell surface
      proteolysis of the 55-kDa MT1-MMP species occurs in the absence of active MMP-2,
      suggesting MT1-MMP autolysis. Cellular invasion of type I collagen matrices
      requires collagenase activity, is blocked by tissue inhibitor of
      metalloproteinases-2 (TIMP-2) and collagenase-resistant collagen, is unaffected
      by TIMP-1, and is accompanied by pro-MMP-2 activation. Together, these data
      indicate that integrin stimulation of MT1-MMP activity is a rate-limiting step
      for type I collagen invasion and provide a mechanism by which this activity can
      be down-regulated following collagen clearance.

PMID- 11331273
TI  - Smad proteins suppress CCAAT/enhancer-binding protein (C/EBP) beta- and STAT3
      mediated transcriptional activation of the haptoglobin promoter.
AB  - Activin A, a member of the transforming growth factor beta (TGFbeta) superfamily,
      blocks interleukin (IL)-6 biological functions. The molecular basis of the
      influence of this TGFbeta signaling on the IL-6 receptor triggered cascade is
      unknown. We studied IL-6-induced secretion of the acute phase protein haptoglobin
      by hepatoma cells. Overexpression of the C/EBPbeta gene, a downstream effector in
      the IL-6 pathway, activated transcription from the haptoglobin promoter. This was
      abolished by either a constitutively active form of activin A type IB receptor
      (CAactRIB) or by a combination of Smad3 and Smad4. Similarly, Smads abolished
      transcriptional activation by co-stimulation with IL-6 and STAT3. The
      transcription co-activator p300 partially overcame the suppressive effect of
      Smads. Electrophoretic mobility shift assays indicated that C/EBPbeta binding to
      haptoglobin promoter DNA was reduced by over-expression of CAactRIB and Smad4. We
      thus show that Smad proteins operate as transcription inhibitors on target genes
      of the IL-6 induced pathway. The effect of Smads is exerted on components of the
      transcription activation complex and may also involve interference with DNA
      binding. This study thus depicts molecular sites of interaction between the
      TGFbeta superfamily and the IL-6 signaling cascades.

PMID- 11331274
TI  - Vitreoscilla hemoglobin. Intracellular localization and binding to membranes.
AB  - The obligate aerobic bacterium, Vitreoscilla, synthesizes elevated quantities of
      a homodimeric hemoglobin (VHb) under hypoxic growth conditions. Expression of VHb
      in heterologous hosts often enhances growth and product formation. A role in
      facilitating oxygen transfer to the respiratory membranes is one explanation of
      its cellular function. Immunogold labeling of VHb in both Vitreoscilla and
      recombinant Escherichia coli bearing the VHb gene clearly indicated that VHb has
      a cytoplasmic (not periplasmic) localization and is concentrated near the
      periphery of the cytosolic face of the cell membrane. OmpA signal-peptide VHb
      fusions were transported into the periplasm in E. coli, but this did not confer
      any additional growth advantage. The interaction of VHb with respiratory
      membranes was also studied. The K(d) values for the binding of VHb to
      Vitreoscilla and E. coli cell membranes were approximately 5-6 microm, a 4-8-fold
      higher affinity than those of horse myoglobin and hemoglobin for these same
      membranes. VHb stimulated the ubiquinol-1 oxidase activity of inverted
      Vitreoscilla membranes by 68%. The inclusion of Vitreoscilla cytochrome bo in
      proteoliposomes led to 2.4- and 6-fold increases in VHb binding affinity and
      binding site number, respectively, relative to control liposomes, suggesting a
      direct interaction between VHb and cytochrome bo.

PMID- 11331275
TI  - Vitamin D(3)-induced apoptosis of murine squamous cell carcinoma cells. Selective
      induction of caspase-dependent MEK cleavage and up-regulation of MEKK-1.
AB  - Vitamin D(3) inhibits cell growth and induces apoptosis in several human cancer
      lines in vitro and in vivo. However, little is known about the molecular events
      involved in vitamin D(3)-induced apoptosis. Here, we demonstrate that the growth
      promoting/pro-survival signaling molecule mitogen-activated protein kinase kinase
      (MEK) is cleaved in a caspase-dependent manner in murine squamous cell carcinoma
      (SCC) cells induced to undergo apoptosis by treatment with vitamin D(3). Cleavage
      resulted in nearly complete loss of full-length MEK and ERK1/2 phosphorylation.
      ERK1/2 expression was affected only slightly. The phosphorylation and expression
      of Akt, a kinase regulating a second cell survival pathway, was also inhibited
      after treatment with vitamin D(3). However, the pro-apoptotic signaling molecule
      MEKK-1 was up-regulated in both apoptotic and non-apoptotic cells with greater
      induction and partial N-terminal proteolysis of MEKK-1 observed in apoptotic
      cells. In contrast to vitamin D(3), cisplatin and etoposide down-regulated Akt
      levels only modestly, did not promote significant loss of MEK expression, and did
      not up-regulate MEKK-1. We propose that vitamin D(3) induces apoptosis in SCC
      cells by a unique mechanism involving selective caspase-dependent MEK cleavage
      and up-regulation of MEKK-1. Additional evidence is provided that vitamin D(3)
      induced apoptosis may be mediated via p38 MAPK.

PMID- 11331276
TI  - Zinc inhibition of protein trans-splicing and identification of regions essential
      for splicing and association of a split intein*.
AB  - Two important aspects of protein splicing were investigated by employing the
      trans-splicing intein from the dnaE gene of Synechocystis sp. PCC6803. First, we
      demonstrated that both protein splicing and cleavage at the N-terminal splice
      junction were inhibited in the presence of zinc ion. The trans-splicing reaction
      was partially blocked at a concentration of 1-10 microm Zn(2+) and completely
      inhibited at 100 microm Zn(2+); the inhibition by zinc was reversed in the
      presence of ethylenediaminetetraacetic acid. We propose that inactivation of
      Cys(160) at the C-terminal splice junction by the chelation of zinc affects both
      the N-S acyl rearrangement and the transesterification steps in the splicing
      pathway. Furthermore, in vivo and in vitro assays were established for the
      determination of intein residues and regions required for splicing or association
      between the N- and C-terminal intein halves. N-terminal truncation of the intein
      C-terminal segment inhibited both splicing and association activities, suggesting
      this region is crucial for the formation of an interface between the two intein
      halves. The replacement of conserved residues in blocks B and F with alanine
      abolished splicing but allowed for association. This is the first evidence
      showing that the conserved residues in block F are required for protein splicing.

PMID- 11331277
TI  - Binding of low density lipoproteins to lipoprotein lipase is dependent on lipids
      but not on apolipoprotein B.
AB  - Lipoprotein lipase (LPL) efficiently mediates the binding of lipoprotein
      particles to lipoprotein receptors and to proteoglycans at cell surfaces and in
      the extracellular matrix. It has been proposed that LPL increases the retention
      of atherogenic lipoproteins in the vessel wall and mediates the uptake of
      lipoproteins in cells, thereby promoting lipid accumulation and plaque formation.
      We investigated the interaction between LPL and low density lipoproteins (LDLs)
      with special reference to the protein-protein interaction between LPL and
      apolipoprotein B (apoB). Chemical modification of lysines and arginines in apoB
      or mutation of its main proteoglycan binding site did not abolish the interaction
      of LDL with LPL as shown by surface plasmon resonance (SPR) and by experiments
      with THP-I macrophages. Recombinant LDL with either apoB100 or apoB48 bound with
      similar affinity. In contrast, partial delipidation of LDL markedly decreased
      binding to LPL. In cell culture experiments, phosphatidylcholine-containing
      liposomes competed efficiently with LDL for binding to LPL. Each LDL particle
      bound several (up to 15) LPL dimers as determined by SPR and by experiments with
      THP-I macrophages. A recombinant NH(2)-terminal fragment of apoB (apoB17) bound
      with low affinity to LPL as shown by SPR, but this interaction was completely
      abolished by partial delipidation of apoB17. We conclude that the LPL-apoB
      interaction is not significant in bridging LDL to cell surfaces and matrix
      components; the main interaction is between LPL and the LDL lipids.

PMID- 11331278
TI  - Oxidative preconditioning and apoptosis in L-cells. Roles of protein kinase B and
      mitogen-activated protein kinases.
AB  - Oxidative stress can cause significant cell death by apoptosis. We performed
      studies in L-cells to explore whether prior exposure to oxidative stress
      ("oxidative preconditioning") can protect the cell against the apoptotic
      consequences of subsequent oxidative insults and to establish the mediators in
      the preconditioning signaling cascade. Cells were preconditioned with three 5-min
      exposures to H(2)O(2), followed by 10-h recovery and subsequent exposure to 600
      microm H(2)O(2) for 10 h. A single 10-h exposure to H(2)O(2) induced substantial
      apoptotic cell death (approximately 90%), as determined by enzyme-linked
      immunosorbent assay, TUNEL (terminal deoxyribonucleotide transferase-mediated
      dUTP nick end labeling), and Annexin V methods, but apoptosis was largely
      prevented in preconditioned cells. The degree of cytoprotection depended on the
      strength of preconditioning or H(2)O(2) concentration (20 approximately 600
      microm). Transient increases in mitogen-activated protein kinase (MAPK), p38, and
      JNK/SAPK activities and sustained protein kinase B (Akt) activation, accompanied
      by drastically reduced caspase 3 activity, were seen after preconditioning. The
      expression levels of these kinases were unaltered. Inhibitors of p38 (SB203580)
      and phosphoinositide 3-kinase (PI3K, LY294002) pathways abolished the protection
      provided by preconditioning. We conclude that oxidative preconditioning protects
      cells against apoptosis and that this effect involves MAPK and PI3K/Akt pathways.
      This system may be important in regulating apoptotic cell death in development
      and disease states.

PMID- 11331279
TI  - A novel bipartite intronic splicing enhancer promotes the inclusion of a mini
      exon in the AMP deaminase 1 gene.
AB  - Alternative splicing of the 12-base exon 2 of the adenosine monophosphate
      deaminase (AMPD) gene is subject to regulation by both cis- and trans-regulatory
      signals. The extent of exon 2 inclusion is stage- and cell type-specific and is
      subject to the physiological state of the cell. In adult skeletal muscle, a cell
      type that regulates the activity of this allosteric enzyme at several levels, the
      exon 2-plus form of AMPD, predominates. We have performed a systematic analysis
      of the cis-acting regulatory sequences that reside in the intron immediately
      downstream of this mini-exon. A complex element comprising sequences that enhance
      exon 2 inclusion and sequences that counteract this effect resides in the middle
      of this intron. We demonstrate that the enhancing component is bipartite, with
      more than a kilobase of sequence separating the two functional sites. The
      presence of even minimal levels the mini-exon in the fully processed AMPD mRNA
      requires both of these sites, neither of which appears in any other published
      splicing enhancer. An RNA binding activity derived from a muscle cell line
      requires both of the enhancing sites. Mutations in either of the sites that
      eliminate exon 2 inclusion abrogate this binding activity.

PMID- 11331280
TI  - Integrin alpha(v)beta(3)/vitronectin interaction affects expression of the
      urokinase system in human ovarian cancer cells.
AB  - The urokinase type plasminogen activator (uPA), together with its receptor uPAR
      and the plasminogen activator inhibitor type-1 (PAI-1) plays a pivotal role
      during tumor invasion and metastasis. Integrins, via interaction with the
      extracellular matrix (ECM), control cell adhesion and motility. The two systems
      are functionally linked because uPAR and PAI-1 bind to the ECM component
      vitronectin (VN). Because integrin signaling alters gene expression patterns, we
      investigated whether the expression levels of uPA, uPAR, and PAI-1 are affected
      by ECM/integrin interactions. Expression of uPA, uPAR, and PAI-1 was
      significantly enhanced when human ovarian cancer cells (OV-MZ-6) were cultivated
      on fibronectin or collagen type IV. In contrast, VN induced down-regulation of
      uPA and uPAR while increasing PAI-1 by up to 4-fold. VN-dependent decrease of uPA
      protein was paralleled by a significant reduction of uPA promoter activity that
      was even more pronounced upon alpha(v)beta(3) overexpression and depended on the
      presence of intact Rel protein-binding sites. The activity of Rel transcription
      factors was also significantly reduced upon alpha(v)beta(3)-mediated cell
      adhesion to VN. The activity of the Rel-unresponsive PAI-1 promoter was up to 5
      fold induced as a function of alpha(v)beta(3)/VN interaction. Thus, the balance
      between available concentrations of uPA, uPAR, PAI-1, and integrins in human
      ovarian cancer cells might provide a switch within the regulation of their
      invasive phenotype.

PMID- 11331281
TI  - Regulation of interferon and retinoic acid-induced cell death activation through
      thioredoxin reductase.
AB  - Interferons (IFNs) and retinoids are potent biological response modifiers. The
      IFN-beta and all-trans-retinoic acid combination, but not these single agents
      individually, induces death in several tumor cell lines. To elucidate the
      molecular basis for these actions, we have employed an antisense knockout
      approach to identify the gene products that mediate cell death and isolated
      several genes associated with retinoid-IFN-induced mortality (GRIMs). One of the
      GRIM cDNAs, GRIM-12, was identical to human thioredoxin reductase (TR). To define
      the functional relevance of TR to cell death and to define its mechanism of death
      modulating functions, we generated mutants of TR and studied their influence on
      the IFN/RA-induced death regulatory functions of caspases. Wild-type TR activates
      cell death that was inhibited in the presence of caspase inhibitors or
      catalytically inactive caspases. A mutant TR, lacking the active site cysteines,
      inhibits the cell death induced by caspase 8. IFN/all-trans-retinoic acid-induced
      cytochrome c release from the mitochondrion was promoted in the presence of wild
      type and was inhibited in the presence of mutant TR. We find that TR modulates
      the activity of caspase 8 to promote death. This effect is in part caused by the
      stimulation of death receptor gene expression. These studies identify a new
      mechanism of cell death regulation by the IFN/all-trans-retinoic acid combination
      involving redox enzymes.

PMID- 11331282
TI  - Microtubules are involved in glucose-dependent dissociation of the yeast vacuolar
      [H+]-ATPase in vivo.
AB  - The vacuolar [H(+)]-ATPases (V-ATPases) are composed of a peripheral V(1) domain
      and a membrane-embedded V(0) domain. Reversible dissociation of the V(1) and V(0)
      domains has been observed in both yeast and insects and has been suggested to
      represent a general regulatory mechanism for controlling V-ATPase activity in
      vivo. In yeast, dissociation of the V-ATPase is triggered by glucose depletion,
      but the signaling pathways that connect V-ATPase dissociation and glucose
      metabolism have not been identified. We have found that nocodazole, an agent that
      disrupts microtubules, partially blocked dissociation of the V-ATPase in response
      to glucose depletion in yeast. By contrast, latrunculin, an agent that disrupts
      actin filaments, had no effect on glucose-dependent dissociation of the V-ATPase
      complex. Neither nocodazole nor latrunculin blocked reassembly of the V-ATPase
      upon re-addition of glucose to the medium. The effect of nocodazole appears to be
      specifically through disruption of microtubules since glucose-dependent
      dissociation of the V-ATPase was not blocked by nocodazole in yeast strains
      bearing a mutation in tubulin that renders it resistant to nocodazole. Because
      nocodazole has been shown to arrest cells in the G(2) phase of the cell cycle, it
      was of interest to determine whether nocodazole exerted its effect on
      dissociation of the V-ATPase through cell cycle arrest. Glucose-dependent
      dissociation of the V-ATPase was examined in four yeast strains bearing
      temperature-sensitive mutations that arrest cells in different stages of the cell
      cycle. Because dissociation of the V-ATPase occurred normally at both the
      permissive and restrictive temperatures in these mutants, the results suggest
      that in vivo dissociation is not dependent upon cell cycle phase.

PMID- 11331283
TI  - Structure of Ala(20) --> Pro/Pro(64) --> Ala substituted subunit c of Escherichia
      coli ATP synthase in which the essential proline is switched between
      transmembrane helices.
AB  - The structure of the A20P/P64A mutated subunit c of Escherichia coli ATP
      synthase, in which the essential proline has been switched from residue 64 of the
      second transmembrane helix (TMH) to residue 20 of the first TMH, has been solved
      by (15)N,(1)H NMR in a monophasic chloroform/methanol/water (4:4:1) solvent
      mixture. The cA20P/P64A mutant grows as well as wild type, and the F(0)F(1)
      complex is fully functional in ATPase-coupled H(+) pumping. Residues 20 and 64
      lie directly opposite to each other in the hairpin-like structure of wild type
      subunit c, and the prolinyl 64 residue is thought to induce a slight bend in TMH
      2 such that it wraps around a more straightened TMH-1. In solution, the A20P/P64A
      substituted subunit c also forms a hairpin of two alpha-helices, with residues 41
      45 forming a connecting loop as in the case of the wild type protein, but, in
      this case, Pro(20) induces a bend in TMH-1, which then packs against a more
      straightened TMH-2. The essential prolinyl residue, whether at position 64 or 20,
      lies close to the aspartyl 61 H(+) binding site. The prolinyl residue may
      introduce structural flexibility in this region of the protein, which may be
      necessary for the proposed movement of the alpha-helical segments during the
      course of the H(+) pumping catalytic cycle.

PMID- 11331284
TI  - The orphan nuclear receptor LRH-1 potentiates the sterol-mediated induction of
      the human CETP gene by liver X receptor.
AB  - The human cholesteryl ester transfer protein (CETP) transfers cholesteryl esters
      from high density lipoproteins to triglyceride-rich lipoproteins, indirectly
      facilitating cholesteryl esters uptake by the liver. Hepatic CETP gene expression
      is increased in response to dietary hypercholesterolemia, an effect that is
      mediated by the activity of liver X receptor/retinoid X receptor (LXR/RXR) on a
      direct repeat 4 element in the CETP promoter. In this study we show that the
      orphan nuclear receptor LRH-1 also transactivates the CETP promoter by binding to
      a proximal promoter element distinct from the DR4 site. LRH-1 potentiates the
      sterol-dependent regulation of the wild type CETP promoter by LXR/RXR. Small
      heterodimer partner, a repressor of LRH-1, abolishes the potentiation effect of
      LRH-1 but not its basal transactivation of the CETP promoter. Since this mode of
      regulation of CETP is very similar to that recently reported for the bile salt
      mediated repression of Cyp7a (encoding the rate-limiting enzyme for conversion of
      cholesterol into bile acid in the liver), we examined the effects of bile salt
      feeding on CETP mRNA expression in human CETP transgenic mice. Hepatic CETP mRNA
      expression was repressed by a diet containing 1% cholic acid in male mice but was
      induced by the same diet in female mice. Microarray analysis of hepatic mRNA
      showed that about 1.5% of genes were repressed, and 2.5% were induced by the bile
      acid diet. However, the sexually dimorphic regulatory pattern of the CETP gene
      was an unusual response. Our data provide further evidence for the regulation of
      CETP and Cyp7a genes by similar molecular mechanisms, consistent with coordinate
      transcriptional regulation of sequential steps of reverse cholesterol transport.
      However, differential effects of the bile salt diet indicate additional
      complexity in the response of these two genes.

PMID- 11331285
TI  - Modulation of the G protein regulator phosducin by Ca2+/calmodulin-dependent
      protein kinase II phosphorylation and 14-3-3 protein binding.
AB  - Phototransduction is a canonical G protein-mediated cascade of retinal
      photoreceptor cells that transforms photons into neural responses. Phosducin (Pd)
      is a Gbetagamma-binding protein that is highly expressed in photoreceptors. Pd is
      phosphorylated in dark-adapted retina and is dephosphorylated in response to
      light. Dephosphorylated Pd binds Gbetagamma with high affinity and inhibits the
      interaction of Gbetagamma with Galpha or other effectors, whereas phosphorylated
      Pd does not. These results have led to the hypothesis that Pd down-regulates the
      light response. Consequently, it is important to understand the mechanisms of
      regulation of Pd phosphorylation. We have previously shown that phosphorylation
      of Pd by cAMP-dependent protein kinase moderately inhibits its association with
      Gbetagamma. In this study, we report that Pd was rapidly phosphorylated by
      Ca(2+)/calmodulin-dependent kinase II, resulting in 100-fold greater inhibition
      of Gbetagamma binding than cAMP-dependent protein kinase phosphorylation.
      Furthermore, Pd phosphorylation by Ca(2+)/calmodulin-dependent kinase II at Ser
      54 and Ser-73 led to binding of the phosphoserine-binding protein 14-3-3.
      Importantly, in vivo decreases in Ca(2+) concentration blocked the interaction of
      Pd with 14-3-3, indicating that Ca(2+) controls the phosphorylation state of Ser
      54 and Ser-73 in vivo. These results are consistent with a role for Pd in Ca(2+)
      dependent light adaptation processes in photoreceptor cells and also suggest
      other possible physiological functions.

PMID- 11331286
TI  - Use of the tetracycline-controlled transcriptional silencer (tTS) to eliminate
      transgene leak in inducible overexpression transgenic mice.
AB  - The doxycycline-inducible reverse tetracycline transactivator (rtTA) is
      frequently used to overexpress transgenes in a temporally regulated fashion in
      vivo. These systems are, however, often limited by the levels of transgene
      expression in the absence of dox administration. The tetracycline-controlled
      transcriptional silencer (tTS), a fusion protein containing the tet repressor and
      the KRAB-AB domain of the kid-1 transcriptional repressor, is inhibited by
      doxycycline. We hypothesized that tTS would tighten control of transgene
      expression in rtTA-based systems. To test this hypothesis we generated mice in
      which the CC10 promoter targeted tTS to the lung, bred these mice with CC10-rtTA
      interleukin 13 (IL-13) mice in which IL-13 was overexpressed in an inducible lung
      specific fashion, and compared the IL-13 production and phenotypes of parental
      mice and the triple transgenic CC10-rtTA/tTS-IL-13 progeny of these crosses. In
      the CC10-rtTA-IL-13 mice, IL-13, mucus metaplasia, inflammation, alveolar
      enlargement, and enhanced lung volumes were noted at base line and increased
      greatly after doxycycline administration. In the triple transgenic tTS animals,
      IL-13 and the IL-13-induced phenotype could not be appreciated without
      doxycycline. In contrast, tTS did not alter the induction of IL-13 or the
      generation of the IL-13 phenotype by doxycycline. Thus, tTS effectively
      eliminated the baseline leak without altering the inducibility of rtTA-regulated
      transgenes in vivo. Optimal "off/on" regulation of transgene expression can be
      accomplished with the combined use of tTS and rtTA.

PMID- 11331287
TI  - DNA ligase I and proliferating cell nuclear antigen form a functional complex.
AB  - DNA ligase I is responsible for joining Okazaki fragments during DNA replication.
      An additional proposed role for DNA ligase I is sealing nicks generated during
      excision repair. Previous studies have shown that there is a physical interaction
      between DNA ligase I and proliferating cell nuclear antigen (PCNA), another
      important component of DNA replication and repair. The results shown here
      indicate that human PCNA enhances the reaction rate of human DNA ligase I up to 5
      fold. The stimulation is specific to DNA ligase I because T4 DNA ligase is not
      affected. Electrophoretic mobility shift assays indicate that PCNA improves the
      binding of DNA ligase I to the ligation site. Increasing the DNA ligase I
      concentration leads to a reduction in PCNA stimulation, consistent with PCNA
      directed improvement of DNA ligase I binding to its DNA substrate. Two
      experiments show that PCNA is required to encircle duplex DNA to enhance DNA
      ligase I activity. Biotin-streptavidin conjugations at the ends of a linear
      substrate inhibit PCNA stimulation. PCNA cannot enhance ligation on a circular
      substrate without the addition of replication factor C, which is the protein
      responsible for loading PCNA onto duplex DNA. These results show that PCNA is
      responsible for the stable association of DNA ligase I to nicked duplex DNA.

PMID- 11331288
TI  - The homeodomain proteins PBX and MEIS1 are accessory factors that enhance thyroid
      hormone regulation of the malic enzyme gene in hepatocytes.
AB  - Triiodothyronine (T3) stimulates a robust increase (>40-fold) in transcription of
      the malic enzyme gene in chick embryo hepatocytes. Previous work has shown that
      optimal T3 regulation of malic enzyme transcription is dependent on the presence
      of an accessory element (designated as region E) that immediately flanks a
      cluster of five T3 response elements in the malic enzyme gene. Here, we have
      analyzed the binding of nuclear proteins to region E and investigated the
      mechanism by which region E enhances T3 responsiveness. In nuclear extracts from
      hepatocytes, region E binds heterodimeric complexes consisting of the homeodomain
      proteins PBX and MEIS1. Region E contains four consecutive PBX/MEIS1 half-sites.
      PBX-MEIS1 heterodimers bind the first and second half-sites, the third and fourth
      half-sites, and the first and fourth half-sites. The configuration conferring the
      greatest increase in T3 responsiveness consists of the first and fourth half
      sites that are separated by 7 nucleotides. Stimulation of T3 response element
      functions by region E does not require the presence of additional malic enzyme
      sequences. In pull-down experiments, PBX1a and PBX1b specifically bind the
      nuclear T3 receptor-alpha, and this interaction is enhanced by the presence of
      T3. A T3 receptor-alpha region containing the DNA binding domain plus flanking
      sequences (amino acids 21-157) is necessary and sufficient for binding to PBX1a
      and PBX1b. These results indicate that PBX-MEIS1 complexes interact with nuclear
      T3 receptors to enhance T3 regulation of malic enzyme transcription in
      hepatocytes.

PMID- 11331289
TI  - The p53-regulated cyclin-dependent kinase inhibitor, p21 (cip1, waf1, sdi1), is
      not required for global genomic and transcription-coupled nucleotide excision
      repair of UV-induced DNA photoproducts.
AB  - The p53 tumor suppressor gene is a transcriptional activator involved in cell
      cycle regulation, apoptosis, and DNA repair. We have shown that p53 is required
      for efficient nucleotide excision repair of UV-induced DNA photoproducts from
      global genomic DNA but has no effect on transcription-coupled repair. In order to
      evaluate whether p53 influences repair indirectly through cell cycle arrest
      following DNA damage or plays a direct role, we examined repair in vivo in human
      cells genetically altered to disrupt or regulate the function of p53 and p21.
      Both primary human fibroblasts and HCT116 colon carcinoma cells wild type for p53
      but in which the p21 gene was inactivated through targeted homologous
      recombination showed no decrease in global repair of UV photoproducts. Human
      bladder carcinoma cells mutant for p53 and containing a tetracycline-regulated
      p21 cDNA showed no significant enhancement of repair upon induction of p21
      expression. All of the cell lines, including the mismatch repair-deficient, MLH1
      mutant HCT116 cells, were proficient for transcription-coupled repair. Clonogenic
      survival of HCT116 cells following UV irradiation showed no dependence on p21.
      Therefore, our results indicate that p53-dependent nucleotide excision repair
      does not require the function of the p21 gene product and is independent of p53
      regulated cell cycle checkpoints.

PMID- 11331290
TI  - Implications for isoform-selective inhibitor design derived from the binding mode
      of bulky isothioureas to the heme domain of endothelial nitric-oxide synthase.
AB  - Nitric oxide produced by nitric-oxide synthase (NOS) is not only involved in a
      wide range of physiological functions but also in a variety of pathological
      conditions. Isoform-selective NOS inhibitors are highly desirable to regulate the
      NO production of one isoform beneficial to normal physiological functions from
      the uncontrolled NO production of another isoform that accompanies certain
      pathological states. Crystal structures of the heme domain of the three NOS
      isoforms have revealed a very high degree of similarity in the immediate vicinity
      of the heme active site illustrating the challenge of isoform-selective inhibitor
      design. Isothioureas are potent NOS inhibitors, and the structures of the
      endothelial NOS heme domain complexed with isothioureas bearing small S-alkyl
      substituents have been determined (Li, H., Raman, C.S., Martasek, P., Kral, V.,
      Masters, B.S.S., and Poulos, T.L. (2000) J. Inorg. Biochem. 81, 133--139). In the
      present communication, the binding mode of larger bisisothioureas complexed to
      the endothelial NOS heme domain has been determined. These structures afford a
      structural rationale for the known inhibitory activities. In addition, these
      structures provide clues on how to exploit the longer inhibitor substituents that
      extend out of the active site pocket for isoform-selective inhibitor design.

PMID- 11331291
TI  - Phosphorylation regulates the interaction between Gln3p and the nuclear import
      factor Srp1p.
AB  - Gln3p is a GATA-type transcription activator of nitrogen catabolite repressible
      (NCR) genes. Gln3p was recently found to be hyperphosphorylated in a TOR
      dependent manner and resides in the cytoplasm in high quality nitrogen. In
      contrast, during nitrogen starvation or rapamycin treatment, Gln3p becomes
      rapidly dephosphorylated and accumulates in the nucleus, thereby activating
      nitrogen catabolite repression genes. However, a detailed mechanistic
      understanding is lacking for the regulation of Gln3p nucleocytoplasmic
      distribution. In this study, we applied a functional genomics approach to
      identify the nuclear transport factors for Gln3p. We found that yeast karyopherin
      alpha/Srp1p and Crm1p are required for the nuclear import and export of Gln3p,
      respectively. Similarly, the Ran GTPase pathway is also involved in the nuclear
      translocation of Gln3p. Finally, we show that Srp1p preferentially interacts with
      the hypophosphorylated versus the hyperphosphorylated Gln3p. These findings
      define a possible mechanism for regulated nucleocytoplasmic transport of Gln3p by
      phosphorylation in vivo.

PMID- 11331292
TI  - Phe-308 and Phe-312 in transmembrane domain 7 are major sites of alpha 1
      adrenergic receptor antagonist binding. Imidazoline agonists bind like
      antagonists.
AB  - Although agonist binding in adrenergic receptors is fairly well understood and
      involves residues located in transmembrane domains 3 through 6, there are few
      residues reported that are involved in antagonist binding. In fact, a major
      docking site for antagonists has never been reported in any G-protein coupled
      receptor. It has been speculated that antagonist binding is quite diverse
      depending upon the chemical structure of the antagonist, which can be quite
      different from agonists. We now report the identification of two phenylalanine
      residues in transmembrane domain 7 of the alpha(1a)-adrenergic receptor (Phe-312
      and Phe-308) that are a major site of antagonist affinity. Mutation of either Phe
      308 or Phe-312 resulted in significant losses of affinity (4-1200-fold) for the
      antagonists prazosin, WB4101, BMY7378, (+) niguldipine, and 5-methylurapidil,
      with no changes in affinity for phenethylamine-type agonists such as epinephrine,
      methoxamine, or phenylephrine. Interestingly, both residues are involved in the
      binding of all imidazoline-type agonists such as oxymetazoline, cirazoline, and
      clonidine, confirming previous evidence that this class of ligand binds
      differently than phenethylamine-type agonists and may be more antagonist-like,
      which may explain their partial agonist properties. In modeling these
      interactions with previous mutagenesis studies and using the current backbone
      structure of rhodopsin, we conclude that antagonist binding is docked higher in
      the pocket closer to the extracellular surface than agonist binding and appears
      skewed toward transmembrane domain 7.

PMID- 11331293
TI  - Configuration and dynamics of xanthophylls in light-harvesting antennae of higher
      plants. Spectroscopic analysis of isolated light-harvesting complex of
      photosystem II and thylakoid membranes.
AB  - Resonance Raman excitation spectroscopy combined with ultra low temperature
      absorption spectral analysis of the major xanthophylls of higher plants in
      isolated antenna and intact thylakoid membranes was used to identify carotenoid
      absorption regions and study their molecular configuration. The major electronic
      transitions of the light-harvesting complex of photosystem II (LHCIIb)
      xanthophylls have been identified for both the monomeric and trimeric states of
      the complex. One long wavelength state of lutein with a 0-0 transition at 510 nm
      was detected in LHCIIb trimers. The short wavelength 0-0 transitions of lutein
      and neoxanthin were located at 495 and 486 nm, respectively. In monomeric LHCIIb,
      both luteins absorb around 495 nm, but slight differences in their protein
      environments give rise to a broadening of this band. The resonance Raman spectra
      of violaxanthin and zeaxanthin in intact thylakoid membranes was determined. The
      broad 0-0 absorption transition for zeaxanthin was found to be located in the 503
      511 nm region. Violaxanthin exhibited heterogeneity, having two populations with
      one absorbing at 497 nm (0-0), 460 nm (0-1), and 429 nm (0-2), and the other
      major pool absorbing at 488 nm (0-0), 452 nm (0-1), and 423 nm (0-2). The origin
      of this heterogeneity is discussed. The configuration of zeaxanthin and
      violaxanthin in thylakoid membranes was different from that of free pigments, and
      both xanthophylls (notably, zeaxanthin) were found to be well coordinated within
      the antenna proteins in vivo, arguing against the possibility of their free
      diffusion in the membrane and supporting our recent biochemical evidence of their
      association with intact oligomeric light-harvesting complexes (Ruban, A. V., Lee,
      P. J., Wentworth, M., Young, A. J., and Horton, P. (1999) J. Biol. Chem. 274,
      10458-10465).

PMID- 11331294
TI  - Identification of an estrogen-inducible phosphatase (PP5) that converts MCF-7
      human breast carcinoma cells into an estrogen-independent phenotype when
      expressed constitutively.
AB  - The proliferation of many estrogen receptor (ER)-positive breast cancer cells
      depends on estradiol, and tumors arising from these cells are often responsive
      initially to treatment with selective ER modulators, which produce an
      antiestrogen effect. However, tumors that are refractory to the antiestrogenic
      effects of selective ER modulators often reemerge, and the prognosis for these
      patients is poor because of the lack of additional effective therapy.
      Accordingly, deciphering the cellular events associated with estrogen-dependent
      growth and the subsequent outgrowth of tumors with an estrogen-independent
      phenotype is of considerable interest. Here we show that the expression of PP5,
      an evolutionarily conserved Ser/Thr phosphatase that functions as an inhibitor of
      glucocorticoid- and p53-induced signaling cascades leading to growth suppression,
      is responsive to 17beta-estradiol (E(2)) in ER-positive human breast carcinoma
      cells (MCF-7). Northern analysis revealed that E(2)-induced PP5 expression is
      blocked by treatment with tamoxifen, and a consensus ER recognition element was
      identified in the PP5 promoter. The PP5-ER recognition element associates with
      human ERs and confers E(2)-induced transcriptional activation to reporter
      plasmids. The specific inhibition of PP5 expression ablates E(2)-mediated
      proliferation in MCF-7 cells without having an apparent effect on E(2)-induced
      expression of c-myc or cyclin D1. Thus, although critical for cell growth, PP5
      likely acts either downstream or independently of c-Myc and Cyclin D1. To further
      characterize the role of PP5 in E(2)-regulated growth control, we constructed
      stable MCF-7 cell lines in which the expression of PP5 was placed under the
      control of tetracycline-regulated transactivator and operator plasmids. Studies
      with these cells revealed that the constitutive overexpression of PP5 affords
      E(2)-dependent MCF-7 cells with the ability to proliferate in E(2)-depleted
      media. Together, these studies indicate that E(2)-induced PP5 expression
      functions to enhance E(2)-initiated signaling cascades leading to cell division
      and that aberrant PP5 expression may contribute to the development of MCF-7 cells
      with an estrogen-independent phenotype.

PMID- 11331295
TI  - SPF30 is an essential human splicing factor required for assembly of the U4/U5/U6
      tri-small nuclear ribonucleoprotein into the spliceosome.
AB  - Spliceosome assembly involves the sequential recruitment of small nuclear
      ribonucleoproteins (snRNPs) onto a pre-mRNA substrate. Although several non-snRNP
      proteins function during the binding of U1 and U2 snRNPs, little is known about
      the subsequent binding of the U4/U5/U6 tri-snRNP. A recent proteomic analysis of
      the human spliceosome identified SPF30 (Neubauer, G., King, A., Rappsilber, J.,
      Calvio, C., Watson, M., Ajuh, P., Sleeman, J., Lamond, A., and Mann, M. (1998)
      Nat. Genet. 20, 46-50), a homolog of the survival of motor neurons (SMN) protein,
      as a spliceosome factor. We show here that SPF30 is a nuclear protein that
      associates with both U4/U5/U6 and U2 snRNP components. In the absence of SPF30,
      the preformed tri-snRNP fails to assemble into the spliceosome. Mass
      spectrometric analysis shows that a recombinant glutathione S-transferase-SPF30
      fusion protein associates with complexes containing core Sm and U4/U5/U6 tri
      snRNP proteins when added to HeLa nuclear extract, most strongly to U4/U6-90. The
      data indicate that SPF30 is an essential human splicing factor that may act to
      dock the U4/U5/U6 tri-snRNP to the A complex during spliceosome assembly or,
      alternatively, may act as a late assembly factor in both the tri-snRNP and the A
      complex.

PMID- 11331296
TI  - Acidic hydrolysis as a mechanism for the cleavage of the Glu(298)-->Asp variant
      of human endothelial nitric-oxide synthase.
AB  - The 894G-->T polymorphism within exon 7 of the human endothelial nitric-oxide
      synthase (eNOS) gene codes for glutamate or aspartate, respectively, at residue
      298 and has been associated with several diseases of cardiovascular origin. A
      recent report indicates that Asp(298)-eNOS (E298D) is cleaved intracellularly to
      100- and 35-kDa fragments, suggesting a mechanism for reduced endothelial
      function. Here we have documented the precise cleavage site of the E298D variant
      as a unique aspartyl-prolyl (Asp(298)--Pro(299)) bond not seen in wild-type eNOS
      (Glu(298)). We show that E298D-eNOS, as isolated from cells and in vitro, is
      susceptible to acidic hydrolysis, and the 100-kDa fragment can be generated ex
      vivo by increasing temperature at low pH. Importantly, cleavage of E298D was
      eliminated using a sample buffer system designed to limit acidic hydrolysis of
      Asp--Pro bonds. These results argue against intracellular processing of E298D
      eNOS and suggest that previously described fragmentation of E298D could be a
      product of sample preparation. We also found that eNOS turnover, NO production,
      and the susceptibility to cellular stress were not different in cells expressing
      WT versus E298D-eNOS. Finally, enzyme activities were identical for the
      respective recombinant enzymes. Thus, intracellular cleavage mechanisms are
      unlikely to account for associations between the exon 7 polymorphism and
      cardiovascular diseases.

PMID- 11331297
TI  - Aggresomes resemble sites specialized for virus assembly.
AB  - The large cytoplasmic DNA viruses such as poxviruses, iridoviruses, and African
      swine fever virus (ASFV) assemble in discrete perinuclear foci called viral
      factories. Factories exclude host proteins, suggesting that they are novel
      subcellular structures induced by viruses. Novel perinuclear structures, called
      aggresomes are also formed by cells in response to misfolded protein (Johnston,
      J.A., C.L. Ward, and R.R. Kopito. 1998. J. Cell Biol. 143:1883--1898; Garcia
      Mata, R., Z. Bebok, E.J. Sorscher, and E.S. Sztul. 1999. J. Cell Biol. 146:1239-
      1254). In this study, we have investigated whether aggresomes and viral factories
      are related structures. Aggresomes were compared with viral factories produced by
      ASFV. Aggresomes and viral factories were located close to the microtubule
      organizing center and required an intact microtubular network for assembly. Both
      structures caused rearrangement of intermediate filaments and the collapse of
      vimentin into characteristic cages, and both recruited mitochondria and cellular
      chaperones. Given that ASFV factories resemble aggresomes, it is possible that a
      cellular response originally designed to reduce the toxicity of misfolded
      proteins is exploited by cytoplasmic DNA viruses to concentrate structural
      proteins at virus assembly sites.

PMID- 11331298
TI  - Negative regulation of the SAPK/JNK signaling pathway by presenilin 1.
AB  - Presenilin 1 (PS1) plays a pivotal role in Notch signaling and the intracellular
      metabolism of the amyloid beta-protein. To understand intracellular signaling
      events downstream of PS1, we investigated in this study the action of PS1 on
      mitogen-activated protein kinase pathways. Overexpressed PS1 suppressed the
      stress-induced stimulation of stress-activated protein kinase (SAPK)/c-Jun NH(2)
      terminal kinase (JNK) in human embryonic kidney 293 cells. Interestingly, two
      functionally inactive PS1 mutants, PS1(D257A) and PS1(D385A), failed to inhibit
      UV-stimulated SAPK/JNK. Furthermore, H(2)O(2-) or UV-stimulated SAPK activity was
      higher in mouse embryonic fibroblast (MEF) cells from PS1-null mice than in MEF
      cells from PS(+/+) mice. MEF(PS1(-/-)) cells were more sensitive to the H(2)O(2)
      induced apoptosis than MEF(PS1(+/+)) cells. Ectopic expression of PS1 in MEF(PS1(
      /-)) cells suppressed H(2)O(2)-stimulated SAPK/JNK activity and apoptotic cell
      death. Together, our data suggest that PS1 inhibits the stress-activated
      signaling by suppressing the SAPK/JNK pathway.

PMID- 11331299
TI  - Inhibitory role of alpha 6 beta 4-associated erbB-2 and phosphoinositide 3-kinase
      in keratinocyte haptotactic migration dependent on alpha 3 beta 1 integrin.
AB  - Keratinocytes and other epithelial cells express two receptors for the basement
      membrane (BM) extracellular matrix component laminin-5 (Ln-5), integrins alpha 3
      beta 1 and alpha 6 beta 4. While alpha 3 beta 1 mediates adhesion, spreading, and
      migration (Kreidberg, J.A. 2000. Curr. Opin. Cell Biol. 12:548--553), alpha 6
      beta 4 is involved in BM anchorage via hemidesmosomes (Borradori, L., and A.
      Sonnenberg. 1999. J. Invest. Dermatol. 112:411--418). We investigated a possible
      regulatory interplay between alpha 3 beta 1 and alpha 6 beta 4 in cell motility
      using HaCaT keratinocytes as a model. We found that alpha 6 beta 4 antibodies
      inhibit alpha 3 beta 1-mediated migration on Ln-5, but only when migration is
      haptotactic (i.e., spontaneous or stimulated by alpha 3 beta 1 activation), and
      not when chemotactic (i.e., triggered by epidermal growth factor receptor).
      Inhibition of migration by alpha 6 beta 4 depends upon phosphoinositide 3-kinase
      (PI3-K) since it is abolished by PI3-K blockers and by dominant-negative PI3-K,
      and constitutively active PI3-K prevents haptotaxis. In HaCaT cells incubated
      with anti-alpha 6 beta 4 antibodies, activation of PI3-K is mediated by alpha 6
      beta 4-associated erbB-2, as indicated by erbB-2 autophosphorylation and erbB
      2/p85 PI3-K coprecipitation. Furthermore, dominant-negative erbB-2 abolishes
      inhibition of haptotaxis by anti-alpha 6 beta 4 antibodies. These results support
      a model whereby (a) haptotactic cell migration on Ln-5 is regulated by concerted
      action of alpha 3beta 1 and alpha 6 beta 4 integrins, (b) alpha 6 beta 4
      associated erbB-2 and PI3-K negatively affect haptotaxis, and (c) chemotaxis on
      Ln-5 is not affected by alpha 6 beta 4 antibodies and may require PI3-K activity.
      This model could be of general relevance to motility of epithelial cells in
      contact with BM.

PMID- 11331300
TI  - Involvement of the lamin rod domain in heterotypic lamin interactions important
      for nuclear organization.
AB  - The nuclear lamina is a meshwork of intermediate-type filament proteins (lamins)
      that lines the inner nuclear membrane. The lamina is proposed to be an important
      determinant of nuclear structure, but there has been little direct testing of
      this idea. To investigate lamina functions, we have characterized a novel lamin
      B1 mutant lacking the middle approximately 4/5 of its alpha-helical rod domain.
      Though retaining only 10 heptads of the rod, this mutant assembles into
      intermediate filament-like structures in vitro. When expressed in cultured cells,
      it concentrates in patches at the nuclear envelope. Concurrently, endogenous
      lamins shift from a uniform to a patchy distribution and lose their complete
      colocalization, and nuclei become highly lobulated. In vitro binding studies
      suggest that the internal rod region is important for heterotypic associations of
      lamin B1, which in turn are required for proper organization of the lamina.
      Accompanying the changes in lamina structure induced by expression of the mutant,
      nuclear pore complexes and integral membrane proteins of the inner membrane
      cluster, principally at the patches of endogenous lamins. Considered together,
      these data indicate that lamins play a major role in organizing other proteins in
      the nuclear envelope and in determining nuclear shape.

PMID- 11331301
TI  - An RGD sequence in the P2Y(2) receptor interacts with alpha(V)beta(3) integrins
      and is required for G(o)-mediated signal transduction.
AB  - The P2Y(2) nucleotide receptor (P2Y(2)R) contains the integrin-binding domain
      arginine-glycine-aspartic acid (RGD) in its first extracellular loop, raising the
      possibility that this G protein-coupled receptor interacts directly with an
      integrin. Binding of a peptide corresponding to the first extracellular loop of
      the P2Y(2)R to K562 erythroleukemia cells was inhibited by antibodies against
      alpha(V)beta(3)/beta(5) integrins and the integrin-associated thrombospondin
      receptor, CD47. Immunofluorescence of cells transfected with epitope-tagged
      P2Y(2)Rs indicated that alpha(V) integrins colocalized 10-fold better with the
      wild-type P2Y(2)R than with a mutant P2Y(2)R in which the RGD sequence was
      replaced with RGE. Compared with the wild-type P2Y(2)R, the RGE mutant required
      1,000-fold higher agonist concentrations to phosphorylate focal adhesion kinase,
      activate extracellular signal-regulated kinases, and initiate the PLC-dependent
      mobilization of intracellular Ca(2+). Furthermore, an anti-alpha(V) integrin
      antibody partially inhibited these signaling events mediated by the wild-type
      P2Y(2)R. Pertussis toxin, an inhibitor of G(i/o) proteins, partially inhibited
      Ca(2+) mobilization mediated by the wild-type P2Y(2)R, but not by the RGE mutant,
      suggesting that the RGD sequence is required for P2Y(2)R-mediated activation of
      G(o), but not G(q). Since CD47 has been shown to associate directly with G(i/o)
      family proteins, these results suggest that interactions between P2Y(2)Rs,
      integrins, and CD47 may be important for coupling the P2Y(2)R to G(o).

PMID- 11331302
TI  - Insights into the dynamic properties of keratin intermediate filaments in living
      epithelial cells.
AB  - The properties of keratin intermediate filaments (IFs) have been studied after
      transfection with green fluorescent protein (GFP)-tagged K18 and/or K8 (type I/II
      IF proteins). GFP-K8 and -K18 become incorporated into tonofibrils, which are
      comprised of bundles of keratin IFs. These tonofibrils exhibit a remarkably wide
      range of motile and dynamic activities. Fluorescence recovery after
      photobleaching (FRAP) analyses show that they recover their fluorescence slowly
      with a recovery t(1/2) of approximately 100 min. The movements of bleach zones
      during recovery show that closely spaced tonofibrils (<1 microm apart) often move
      at different rates and in different directions. Individual tonofibrils frequently
      change their shapes, and in some cases these changes appear as propagated
      waveforms along their long axes. In addition, short fibrils, termed keratin
      squiggles, are seen at the cell periphery where they move mainly towards the cell
      center. The motile properties of keratin IFs are also compared with those of type
      III IFs (vimentin) in PtK2 cells. Intriguingly, the dynamic properties of keratin
      tonofibrils and squiggles are dramatically different from those of vimentin
      fibrils and squiggles within the same cytoplasmic regions. This suggests that
      there are different factors regulating the dynamic properties of different types
      of IFs within the same cytoplasmic regions.

PMID- 11331303
TI  - Merotelic kinetochore orientation is a major mechanism of aneuploidy in mitotic
      mammalian tissue cells.
AB  - In mitotic cells, an error in chromosome segregation occurs when a chromosome is
      left near the spindle equator after anaphase onset (lagging chromosome). In PtK1
      cells, we found 1.16% of untreated anaphase cells exhibiting lagging chromosomes
      at the spindle equator, and this percentage was enhanced to 17.55% after a
      mitotic block with 2 microM nocodazole. A lagging chromosome seen during anaphase
      in control or nocodazole-treated cells was found by confocal immunofluorescence
      microscopy to be a single chromatid with its kinetochore attached to kinetochore
      microtubule bundles extending toward opposite poles. This merotelic orientation
      was verified by electron microscopy. The single kinetochores of lagging
      chromosomes in anaphase were stretched laterally (1.2--5.6-fold) in the
      directions of their kinetochore microtubules, indicating that they were not able
      to achieve anaphase poleward movement because of pulling forces toward opposite
      poles. They also had inactivated mitotic spindle checkpoint activities since they
      did not label with either Mad2 or 3F3/2 antibodies. Thus, for mammalian cultured
      cells, kinetochore merotelic orientation is a major mechanism of aneuploidy not
      detected by the mitotic spindle checkpoint. The expanded and curved crescent
      morphology exhibited by kinetochores during nocodazole treatment may promote the
      high incidence of kinetochore merotelic orientation that occurs after nocodazole
      washout.

PMID- 11331304
TI  - Rapid cycling of lipid raft markers between the cell surface and Golgi complex.
AB  - The endocytic itineraries of lipid raft markers, such as glycosyl
      phosphatidylinositol (GPI)-anchored proteins and glycosphingolipids, are
      incompletely understood. Here we show that different GPI-anchored proteins have
      different intracellular distributions; some (such as the folate receptor)
      accumulate in transferrin-containing compartments, others (such as CD59 and GPI
      linked green fluorescent protein [GFP]) accumulate in the Golgi apparatus.
      Selective photobleaching shows that the Golgi pool of both GPI-GFP and CD59-GFP
      constantly and rapidly exchanges with the pool of these proteins found on the
      plasma membrane (PM). We visualized intermediates carrying GPI-GFP from the Golgi
      apparatus to the PM and separate structures delivering GPI-GFP to the Golgi
      apparatus.GPI-GFP does not accumulate within endocytic compartments containing
      transferrin, although it is detected in intracellular structures which are
      endosomes by the criteria of accessibility to a fluid phase marker and to cholera
      and shiga toxin B subunits (CTxB and STxB, which are also found in rafts). GPI
      GFP and a proportion of the total CTxB and STxB taken up into cells are
      endocytosed independently of clathrin-associated machinery and are delivered to
      the Golgi complex via indistinguishable mechanisms. Hence, they enter the Golgi
      complex in the same intermediates, get there independently of both clathrin and
      rab5 function, and are excluded from it at 20 degrees C and under conditions of
      cholesterol sequestration. The PM-Golgi cycling pathway followed by GPI-GFP could
      serve to regulate lipid raft distribution and function within cells.

PMID- 11331305
TI  - Lack of pericytes leads to endothelial hyperplasia and abnormal vascular
      morphogenesis.
AB  - The association of pericytes (PCs) to newly formed blood vessels has been
      suggested to regulate endothelial cell (EC) proliferation, survival, migration,
      differentiation, and vascular branching. Here, we addressed these issues using
      PDGF-B-- and PDGF receptor-beta (PDGFR-beta)--deficient mice as in vivo models of
      brain angiogenesis in the absence of PCs. Quantitative morphological analysis
      showed that these mutants have normal microvessel density, length, and number of
      branch points. However, absence of PCs correlates with endothelial hyperplasia,
      increased capillary diameter, abnormal EC shape and ultrastructure, changed
      cellular distribution of certain junctional proteins, and morphological signs of
      increased transendothelial permeability. Brain endothelial hyperplasia was
      observed already at embryonic day (E) 11.5 and persisted throughout development.
      From E 13.5, vascular endothelial growth factor-A (VEGF-A) and other genes
      responsive to metabolic stress became upregulated, suggesting that the abnormal
      microvessel architecture has systemic metabolic consequences. VEGF-A upregulation
      correlated temporally with the occurrence of vascular abnormalities in the
      placenta and dilation of the heart. Thus, although PC deficiency appears to have
      direct effects on EC number before E 13.5, the subsequent increased VEGF-A levels
      may further abrogate microvessel architecture, promote vascular permeability, and
      contribute to formation of the edematous phenotype observed in late gestation
      PDGF-B and PDGFR-beta knock out embryos.

PMID- 11331306
TI  - Delta N89 beta-catenin induces precocious development, differentiation, and
      neoplasia in mammary gland.
AB  - To investigate the role of beta-catenin in mammary gland development and
      neoplasia, we expressed a stabilized, transcriptionally active form of beta
      catenin lacking the NH(2)-terminal 89 amino acids (Delta N 89 beta-catenin) under
      the control of the mouse mammary tumor virus long terminal repeat. Our results
      show that Delta N 89 beta-catenin induces precocious lobuloalveolar development
      and differentiation in the mammary glands of both male and female mice. Virgin
      Delta N 89 beta-catenin mammary glands resemble those found in wild-type (wt)
      pregnant mice and inappropriately express cyclin D1 mRNA. In contrast to wt
      mammary glands, which resume a virgin appearance after cessation of lactation,
      transgenic mammary glands involute to a midpregnant status. All transgenic
      females develop multiple aggressive adenocarcinomas early in life. Surprisingly,
      the Delta N89 beta-catenin phenotype differs from those elicited by
      overexpression of Wnt genes in this gland. In particular, Delta N 89 beta-catenin
      has no effect on ductal side branching. This suggests that Wnt induction of
      ductal branching involves additional downstream effectors or modulators.

PMID- 11331307
TI  - Rho-kinase--mediated contraction of isolated stress fibers.
AB  - It is widely accepted that actin filaments and the conventional double-headed
      myosin interact to generate force for many types of nonmuscle cell motility, and
      that this interaction occurs when the myosin regulatory light chain (MLC) is
      phosphorylated by MLC kinase (MLCK) together with calmodulin and Ca(2+). However,
      recent studies indicate that Rho-kinase is also involved in regulating the smooth
      muscle and nonmuscle cell contractility. We have recently isolated reactivatable
      stress fibers from cultured cells and established them as a model system for
      actomyosin-based contraction in nonmuscle cells. Here, using isolated stress
      fibers, we show that Rho-kinase mediates MLC phosphorylation and their
      contraction in the absence of Ca(2+). More rapid and extensive stress fiber
      contraction was induced by MLCK than was by Rho-kinase. When the activity of Rho
      kinase but not MLCK was inhibited, cells not only lost their stress fibers and
      focal adhesions but also appeared to lose cytoplasmic tension. Our study suggests
      that actomyosin-based nonmuscle contractility is regulated by two kinase systems:
      the Ca(2+)-dependent MLCK and the Rho-kinase systems. We propose that Ca(2+) is
      used to generate rapid contraction, whereas Rho-kinase plays a major role in
      maintaining sustained contraction in cells.

PMID- 11331308
TI  - A new focal adhesion protein that interacts with integrin-linked kinase and
      regulates cell adhesion and spreading.
AB  - Integrin-linked kinase (ILK) is a multidomain focal adhesion (FA) protein that
      functions as an important regulator of integrin-mediated processes. We report
      here the identification and characterization of a new calponin homology (CH)
      domain-containing ILK-binding protein (CH-ILKBP). CH-ILKBP is widely expressed
      and highly conserved among different organisms from nematodes to human. CH-ILKBP
      interacts with ILK in vitro and in vivo, and the ILK COOH-terminal domain and the
      CH-ILKBP CH2 domain mediate the interaction. CH-ILKBP, ILK, and PINCH, a FA
      protein that binds the NH(2)-terminal domain of ILK, form a complex in cells.
      Using multiple approaches (epitope-tagged CH-ILKBP, monoclonal anti-CH-ILKBP
      antibodies, and green fluorescent protein-CH-ILKBP), we demonstrate that CH-ILKBP
      localizes to FAs and associates with the cytoskeleton. Deletion of the ILK
      binding CH2 domain abolished the ability of CH-ILKBP to localize to FAs.
      Furthermore, the CH2 domain alone is sufficient for FA targeting, and a point
      mutation that inhibits the ILK-binding impaired the FA localization of CH-ILKBP.
      Thus, the CH2 domain, through its interaction with ILK, mediates the FA
      localization of CH-ILKBP. Finally, we show that overexpression of the ILK-binding
      CH2 fragment or the ILK-binding defective point mutant inhibited cell adhesion
      and spreading. These findings reveal a novel CH-ILKBP-ILK-PINCH complex and
      provide important evidence for a crucial role of this complex in the regulation
      of cell adhesion and cytoskeleton organization.

PMID- 11331309
TI  - Real time fluorescence imaging of PLC gamma translocation and its interaction
      with the epidermal growth factor receptor.
AB  - The translocation of fluorescently tagged PLC gamma and requirements for this
      process in cells stimulated with EGF were analyzed using real time fluorescence
      microscopy applied for the first time to monitor growth factor receptor--effector
      interactions. The translocation of PLC gamma to the plasma membrane required the
      functional Src homology 2 domains and was not affected by mutations in the
      pleckstrin homology domain or inhibition of phosphatidylinositol (PI) 3-kinase.
      An array of domains specific for PLC gamma isoforms was sufficient for this
      translocation. The dynamics of translocation to the plasma membrane and
      redistribution of PLC gamma, relative to localization of the EGF receptor and PI
      4,5-biphosphate (PI 4,5-P(2)), were shown. Colocalization with the receptor was
      observed in the plasma membrane and in membrane ruffles where PI 4,5-P(2)
      substrate could also be visualized. At later times, internalization of PLC gamma,
      which could lead to separation from the substrate, was observed. The data support
      a direct binding of PLC gamma to the receptor as the main site of the plasma
      membrane recruitment. The presence of PLC gamma in membrane structures and its
      access to the substrate appear to be transient and are followed by a rapid
      incorporation into intracellular vesicles, leading to downregulation of the PLC
      activity.

PMID- 11331310
TI  - Tumor suppressor p53 binding protein 1 (53BP1) is involved in DNA damage
      signaling pathways.
AB  - The tumor suppressor p53 binding protein 1 (53BP1) binds to the DNA-binding
      domain of p53 and enhances p53-mediated transcriptional activation. 53BP1
      contains two breast cancer susceptibility gene 1 COOH terminus (BRCT) motifs,
      which are present in several proteins involved in DNA repair and/or DNA damage
      signaling pathways. Thus, we investigated the potential role of 53BP1 in DNA
      damage-signaling pathways. Here, we report that 53BP1 becomes hyperphosphorylated
      and forms discrete nuclear foci in response to DNA damage. These foci colocalize
      at all time points with phosphorylated H2AX (gamma-H2AX), which has been
      previously demonstrated to localize at sites of DNA strand breaks. 53BP1 foci
      formation is not restricted to gamma-radiation but is also detected in response
      to UV radiation as well as hydroxyurea, camptothecin, etoposide, and
      methylmethanesulfonate treatment. Several observations suggest that 53BP1 is
      regulated by ataxia telangiectasia mutated (ATM) after DNA damage. First, ATM
      deficient cells show no 53BP1 hyperphosphorylation and reduced 53BP1 foci
      formation in response to gamma-radiation compared with cells expressing wild-type
      ATM. Second, wortmannin treatment strongly inhibits gamma-radiation-induced
      hyperphosphorylation and foci formation of 53BP1. Third, 53BP1 is readily
      phosphorylated by ATM in vitro. Taken together, these results suggest that 53BP1
      is an ATM substrate that is involved early in the DNA damage-signaling pathways
      in mammalian cells.

PMID- 11331311
TI  - Mistargeting of B-type lamins at the end of mitosis: implications on cell
      survival and regulation of lamins A/C expression.
AB  - We previously showed that targeting of protein phosphatase 1 (PP1) to the nuclear
      envelope (NE) by the A-kinase anchoring protein, AKAP149, correlates with nuclear
      assembly of B-type lamins in vitro. We demonstrate here that failure of AKAP149
      mediated assembly of B-type lamins into the nuclear lamina at the end of mitosis
      is followed by apoptosis, and induces expression of the gene encoding A-type
      lamins in cells that normally do not express lamins A/C. In HeLa cells,
      inhibition of PP1 association with the NE mediated by a peptide containing the
      PP1-binding domain of AKAP149 results in failure of B-type lamins to assemble,
      and in their rapid caspase-dependent proteolysis. However, assembly of lamins A/C
      is not affected. Nonetheless, apoptosis follows within hours of nuclear
      reformation after mitosis. In lymphoid KE37 cells, which do not express lamins
      A/C, inhibition of B-type lamin assembly triggers rapid synthesis and nuclear
      assembly of both lamins A and C before apoptosis takes place. The results
      indicate that nuclear assembly of B-type lamins is essential for cell survival.
      They also suggest that mistargeting of B-type lamins at the end of mitosis
      elicits a tentative rescue process to assemble a nuclear lamina in lymphoid cells
      that normally do not express lamins A/C.

PMID- 11331312
TI  - Activation of the Arp2/3 complex by the actin filament binding protein Abp1p.
AB  - The actin-related protein (Arp) 2/3 complex plays a central role in assembly of
      actin networks. Because distinct actin-based structures mediate diverse
      processes, many proteins are likely to make spatially and temporally regulated
      interactions with the Arp2/3 complex. We have isolated a new activator, Abp1p,
      which associates tightly with the yeast Arp2/3 complex. Abp1p contains two acidic
      sequences (DDW) similar to those found in SCAR/WASp proteins. We demonstrate that
      mutation of these sequences abolishes Arp2/3 complex activation in vitro. Genetic
      studies indicate that this activity is important for Abp1p functions in vivo. In
      contrast to SCAR/WASp proteins, Abp1p binds specifically to actin filaments, not
      monomers. Actin filament binding is mediated by the ADF/cofilin homology (ADF-H)
      domain of Abp1p and is required for Arp2/3 complex activation in vitro. We
      demonstrate that Abp1p recruits Arp2/3 complex to the sides of filaments,
      suggesting a novel mechanism of activation. Studies in yeast and mammalian cells
      indicate that Abp1p is involved functionally in endocytosis. Based on these
      results, we speculate that Abp1p may link Arp2/3-mediated actin assembly to a
      specific step in endocytosis.

PMID- 11331313
TI  - Lamins and apoptosis: a two-way street?

PMID- 11331314
TI  - Weight gain in early-stage breast cancer: where do we go from here?

PMID- 11331315
TI  - High-dose interferon alfa-2b significantly prolongs relapse-free and overall
      survival compared with the GM2-KLH/QS-21 vaccine in patients with resected stage
      IIB-III melanoma: results of intergroup trial E1694/S9512/C509801.
AB  - PURPOSE: Vaccine alternatives to high-dose interferon alfa-2b therapy (HDI), the
      current standard adjuvant therapy for high-risk melanoma, are of interest because
      of toxicity associated with HDI. The GM2 ganglioside is a well-defined melanoma
      antigen, and anti-GM2 antibodies have been associated with improved prognosis. We
      conducted a prospective, randomized, intergroup trial to evaluate the efficacy of
      HDI for 1 year versus vaccination with GM2 conjugated to keyhole limpet
      hemocyanin and administered with QS-21 (GMK) for 96 weeks (weekly x 4 then every
      12 weeks x 8). PATIENTS AND METHODS: Eligible patients had resected stage IIB/III
      melanoma. Patients were stratified by sex and number of positive nodes. Primary
      end points were relapse-free survival (RFS) and overall survival (OS). RESULTS:
      Eight hundred eighty patients were randomized (440 per treatment group); 774
      patients were eligible for efficacy analysis. The trial was closed after interim
      analysis indicated inferiority of GMK compared with HDI. For eligible patients,
      HDI provided a statistically significant RFS benefit (hazard ratio [HR] = 1.47, P
      = .0015) and OS benefit (HR = 1.52, P = .009) for GMK versus HDI. Similar benefit
      was observed in the intent-to-treat analysis (RFS HR = 1.49; OS HR = 1.38). HDI
      was associated with a treatment benefit in all subsets of patients with zero to >
      or = four positive nodes, but the greatest benefit was observed in the node
      negative subset (RFS HR = 2.07; OS HR = 2.71 [eligible population]). Antibody
      responses to GM2 (ie, titers > or = 1:80) at days 29, 85, 365, and 720 were
      associated with a trend toward improved RFS and OS (P2 = .068 at day 29).
      CONCLUSION: This trial demonstrated a significant treatment benefit of HDI versus
      GMK in terms of RFS and OS in melanoma patients at high risk of recurrence.

PMID- 11331316
TI  - Changes in weight, body composition, and factors influencing energy balance among
      premenopausal breast cancer patients receiving adjuvant chemotherapy.
AB  - PURPOSE: Weight gain is a common problem among breast cancer patients who receive
      adjuvant chemotherapy (CT). We undertook a study to determine the causes of this
      energy imbalance. PATIENTS AND METHODS: Factors related to energy balance were
      assessed at baseline (within 3 weeks of diagnosis) and throughout 1 year
      postdiagnosis among 53 premenopausal women with operable breast carcinoma. Thirty
      six patients received CT and 17 received only localized treatment (LT). Measures
      included body composition (dual energy x-ray absorptiometry), resting energy
      expenditure (REE; indirect calorimetry), dietary intake (2-day dietary recalls
      and food frequency questionnaires) and physical activity (physical activity
      records). RESULTS: Mean weight gain in the LT patients was 1.0 kg versus 2.1 kg
      in the CT group (P =.02). No significant differences between groups in trend over
      time were observed for REE and energy intake; however, a significant difference
      was noted for physical activity (P =.01). Several differences between groups in 1
      year change scores were detected. The mean change (+/- SE) in LT versus CT groups
      and P values for uncontrolled/controlled (age, race, radiation therapy, baseline
      body mass index, and end point under consideration) analysis are as follows:
      percentage of body fat (-0.1 +/- 0.4 v +2.2 +/- 0.6%; P =.001/0.04); fat mass
      (+0.1 +/- 0.3 v +2.3 +/- 0.7 kg; P =.002/0.04); lean body mass (+0.8 +/- 0.2 v 
      0.4 +/- 0.3 kg; P =.02/0.30); and leg lean mass (+0.5 +/- 0.1 v -0.2 +/- 0.1 kg;
      P =.01/0.11). CONCLUSION: These data do not support overeating as a cause of
      weight gain among breast cancer patients who receive CT. The data suggest,
      however, that CT-induced weight gain is distinctive and indicative of sarcopenic
      obesity (weight gain in the presence of lean tissue loss or absence of lean
      tissue gain). The development of sarcopenic obesity with evidence of reduced
      physical activity supports the need for interventions focused on exercise,
      especially resistance training in the lower body, to prevent weight gain.

PMID- 11331317
TI  - Outcomes of treatment of children and adolescents with recurrent non-Hodgkin's
      lymphoma and Hodgkin's disease with dexamethasone, etoposide, cisplatin,
      cytarabine, and l-asparaginase, maintenance chemotherapy, and transplantation:
      Children's Cancer Group Study CCG-5912.
AB  - PURPOSE: To determine the toxicity and response rate in children treated with
      dexamethasone, etoposide, cisplatin, high-dose cytarabine, and L-asparaginase
      (DECAL) for recurrent non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD).
      PATIENTS AND METHODS: Ninety-seven children with recurrent NHL (n = 68) or HD (n
      = 29) were enrolled. Treatment consisted of two cycles of DECAL, then bone marrow
      transplantation or up to four cycles of ifosfamide, mesna, and etoposide
      alternating with DECAL maintenance therapy. RESULTS: After two cycles of DECAL
      induction therapy, complete response (CR) or partial response (PR) was reported
      in 19 (65.5%; 10 CRs and nine PRs) of 29 patients with HD and 29 (41.6%; 23 CRs
      and six PRs) of 68 patients with NHL. When only 24 patients with HD and 58
      patients with NHL who were assessable for response were considered, the response
      rates were 79.2% (19 of 24 patients) and 50.0% (29 of 58 patients), respectively.
      Five-year event-free survival was 26% +/- 9% and 23% +/- 5% in patients with HD
      and NHL, respectively. Five-year survival was 31% +/- 14% and 30% +/- 6%,
      respectively. Although median time to treatment failure was significantly longer
      in patients with HD (EFS, P =.002; survival, P =.011), this difference did not
      translate into a higher long-term survival. Grade 3 or 4 toxic effects were
      observed during induction in 70 (72%) of 97 patients and during maintenance in 45
      (70%) of 64 courses of DECAL therapy. Pancytopenia and systemic infections in
      particular were frequently observed. Other toxic effects were uncommon. Although
      not a formal part of the therapy or the study design, 42 patients who responded
      to therapy who underwent bone marrow transplant did not show any benefit from
      this approach. CONCLUSION: DECAL is an effective and tolerable salvage regimen
      for treating patients with recurrent NHL and HD.

PMID- 11331318
TI  - Testicular disease in childhood B-cell non-Hodgkin's lymphoma: the French Society
      of Pediatric Oncology experience.
AB  - PURPOSE: To investigate whether testicular disease in childhood B-cell lymphoma
      should continue to be considered a sanctuary site, as it is with other lymphoid
      malignancies such as acute lymphoblastic leukemia. PATIENTS AND METHODS: Seven
      hundred forty-two children with B-cell non-Hodgkin's lymphoma were included in
      the LMB protocols of the French Society of Pediatric Oncology from February 1981
      to May 1994. Thirty patients (5.3%) had testicular involvement at diagnosis. We
      describe the clinical presentation and outcome of these 30 patients, who were
      treated without local radiation therapy. RESULTS: Five patients underwent
      diagnostic orchidectomy. The median patient age was 8.5 years (range, 2 to 14
      years), and their cancers were stage III (18 patients), stage IV (five patients),
      and B-cell acute lymphoblastic leukemia (seven patients). Five patients had
      central nervous system involvement. Twenty-eight patients (95%) achieved complete
      remission. Twenty-six patients are alive without progressive disease (median
      follow-up, 6.5 years). CONCLUSION: Testicular disease does not seem to confer a
      poor prognosis, and it is curable with intensive combination chemotherapy alone.
      Local treatment (surgery or radiation) is avoidable; therefore, gonadal function
      can be preserved.

PMID- 11331319
TI  - Alternating hepatic arterial infusion and systemic chemotherapy for liver
      metastases from colorectal cancer: a phase II trial using intermittent
      percutaneous hepatic arterial access.
AB  - PURPOSE: To evaluate the objective response to a short course of hepatic arterial
      infusion (HAI) using temporary, percutaneously placed catheters alternating with
      systemic prolonged continuous infusion fluorouracil (ci 5-FU) and daily oral
      leucovorin (L). PATIENTS AND METHODS: Eligible patients were previously untreated
      (except for adjuvant therapy) adults with liver-predominant metastases, with
      Eastern Cooperative Oncology Group performance status of 0 to 2. Treatment
      regimen included HAI with fluorodeoxyuridine (FUDR) 60 mg/m2/d and L 15 mg/m2/d
      continuously infused daily for 4 days. After a 1-week rest, ci 5-FU was
      administered through a central venous access device using a dose of 180 mg/m2/d
      with a fixed dose of oral L at 5 mg/m2/d for 21 out of 28 days. Cycles were
      repeated every 6 weeks. After four cycles of therapy, patients were maintained on
      ci 5-FU and daily oral L until evidence of progression. RESULTS: Forty-three
      patients were enrolled onto this trial. One patient was ineligible. The objective
      response rate for all patients (17 partial, zero complete) was 41% (95%
      confidence interval [CI], 26% to 56%). Five patients were not able to receive at
      least one complete cycle of HAI. Among patients who received at least one
      complete cycle of HAI, the response rate was 46% (95% CI, 30% to 62%). Five
      patients underwent a liver resection after enrolling onto the protocol. At the
      time of analysis, estimated median time to progression was 6 months, and
      estimated median overall survival was 13 months. CONCLUSION: The objective
      response rate was comparable to that achieved with more prolonged and more
      frequent HAI using FUDR. This approach should be studied as an acceptable
      alternative to surgically placed hepatic arterial catheters/pumps and may have a
      role as neoadjuvant therapy for liver metastases that are unresectable, as well
      as an adjuvant role for patients with resected hepatic metastatic colorectal
      cancer.

PMID- 11331320
TI  - Fluorouracil modulation in colorectal cancer: lack of improvement with N 
      phosphonoacetyl- l -aspartic acid or oral leucovorin or interferon, but enhanced
      therapeutic index with weekly 24-hour infusion schedule--an Eastern Cooperative
      Oncology Group/Cancer and Leukemia Group B Study.
AB  - PURPOSE: To investigate mechanism-directed regimens in maximizing the efficacy of
      fluorouracil (5-FU) in advanced colorected cancer. PATIENTS AND METHODS: Based on
      promising phase II data, a randomized comparison of various methods for the
      biochemical modulation of 5-FU was undertaken in patients with advanced
      colorectal cancer. The control group received single-agent 5-FU as a 24-hour
      infusion weekly. Patients (N = 1,120) with no prior chemotherapy for metastatic
      disease were randomized to one of the following arms: arm A, 5-FU 2,600 mg/m2 by
      24-hour infusion, weekly; arm B, N-phosphonoacetyl-l-aspartic acid 250 mg/m2 day
      l, 5-FU 2,600 mg/m2 by 24-hour infusion day 2, weekly; arm C, 5-FU 600 mg/m2 with
      oral leucovorin (LV) 125 mg/m2 hourly for the preceding 4 hours, weekly; arm D, 5
      FU 600 mg/m2 with intravenous (IV) LV 600 mg/m2, weekly; arm E, 5-FU 750 mg/m2/d
      IV by continuous infusion for 5 days, then 750 mg/m2 weekly, and recombinant
      interferon alfa-2a 9 million units subcutaneously three times weekly. Median
      follow-up was 4.8 years. RESULTS: Of the 1,098 assessable patients, 57% had
      measurable disease. The toxicity of all the regimens was tolerable. Grade 4 or
      worse toxicity occurred in 11%, 11%, 30%, 24%, and 22% on each arm, respectively;
      diarrhea was the most common adverse effect. These toxicity patterns favored
      significantly (P <.001) the 24-hour infusion arms. Median survival (months) by
      arm was A, 14.8; B, 11.9; C, 13.5; D, 13.6; and E, 15.2. These survival durations
      did not differ significantly. CONCLUSION: We conclude that a weekly infusion
      regimen of 5-FU is significantly less toxic than and as effective as 5-FU bolus
      regimens modulated by either LV or interferon in patients with metastatic
      colorectal cancer.

PMID- 11331321
TI  - Differential expression of metastasis-associated genes in papilla of vater and
      pancreatic cancer correlates with disease stage.
AB  - PURPOSE: Papilla of Vater cancer has a much better prognosis than pancreatic
      cancer. It is not known whether this is the result of differences in the tumor
      biology of the two malignancies. Because metastasis formation is a critical step
      in tumor progression and a negative prognostic factor, we compared the expression
      of nm23-H1 and KAI1, two metastasis-suppressing genes, in papilla of Vater cancer
      and pancreatic cancer. PATIENTS AND METHODS: Analysis was performed in nine
      normal human papilla of Vater samples, 27 papilla of Vater cancers, 16 normal
      pancreatic samples, and 29 pancreatic cancers. Expression of nm23-H1 and KAI1 was
      analyzed by Northern blot analysis and in situ hybridization. In addition,
      immunohistochemistry was performed to localize the respective proteins. RESULTS:
      There was no difference in nm23-H1 and KAI1 mRNA expression levels in normal
      versus cancerous papilla of Vater samples. In contrast, nm23-H1 and KAI1 RNA
      expression was upregulated in early tumor stages of pancreatic cancer and reduced
      in advanced tumor stages. When expression of nm23-H1 and KAI1 RNA was analyzed by
      use of in situ hybridization, normal epithelial cells of the papilla of Vater
      exhibited mRNA staining intensity similar to that of papilla of Vater cancer
      cells. Similar levels of nm23-H1 and KAI1 immunoreactivity also were observed in
      these samples. In contrast, early stage pancreatic cancer samples exhibited
      stronger nm23-H1 and KAI1 immunoreactivity than normal controls. Furthermore,
      early pancreatic cancer stages exhibited higher KAI1 and nm23-H1 immunostaining
      than advanced tumor stages. CONCLUSION: Differences in the expression patterns of
      the two tumor suppressor genes nm23-H1 and KAI1 may contribute to the different
      prognoses of papilla of Vater cancer and pancreatic cancer. Our findings support
      the hypothesis that biologic differences rather than earlier diagnosis influence
      the different outcomes of these two tumor entities.

PMID- 11331322
TI  - Addition of oxaliplatin to continuous fluorouracil, l-folinic acid, and
      concomitant radiotherapy in rectal cancer: the Lyon R 97-03 phase I trial.
AB  - PURPOSE: Oxaliplatin could increase the efficacy of fluorouracil (5-FU)/folinic
      acid chemoradiotherapy in rectal cancer. We tested three dose levels to identify
      a feasible oxaliplatin dose for combination therapy. PATIENTS AND METHODS:
      Between February 1998 and April 2000, we included 17 rectal adenocarcinoma
      patients in a single-center phase I study. Patients had T4 rectal carcinoma, T1
      T3 disease with colostomy refusal, or potentially operable T2/T3 M1 requiring
      local treatment. Pelvic radiotherapy was 45 Gy over 5 weeks, 1.8 Gy/fraction,
      with concomitant chemotherapy weeks 1 and 5. Chemotherapy was oxaliplatin 80,
      100, or 130 mg/m2 2-hour infusion on day 1 followed by L-folinic acid 100 mg/m2/d
      intravenous bolus, and 5-FU 350 mg/m2/d continuous infusion on days 1 to 5
      (FolfoR1). Six patients refusing surgery received additional contact radiotherapy
      +/- brachytherapy. Dose escalation proceeded if less than two of six patients had
      dose-limiting toxicity (DLT) at a given dose-level. RESULTS: All except two
      patients completed treatment; patients at level 1 (prolonged grade 1
      thrombocytopenia) and level 3 (prolonged cold-related dysesthesia) had no second
      chemotherapy course. Median follow-up is 14 months (range, 2 to 28 months). One
      elderly patient at dose level 1 had DLT asthenia, severe diarrhea and vomiting,
      and more than 10% weight loss. There were no other DLTs and no severe rectitis or
      gastrointestinal toxicity. There were objective responses at all doses and no
      progressions. Eight patients underwent radical surgery after chemoradiotherapy.
      Two had complete pathologic responses. CONCLUSION: FolfoR1 seems feasible and
      effective. Dose escalation did not increase toxicity. Although the MTD was not
      reached in this study, we recommend oxaliplatin 130 mg/m2 for phase II studies
      because it is the dose determined from studies in metastatic patients with no
      toxicity when given concurrently with radiation.

PMID- 11331323
TI  - Determinants of the use of complementary therapies by patients with cancer.
AB  - PURPOSE: We performed a survey of Israeli oncology patients to examine the extent
      of their use of complementary therapies (CT) and to compare sociodemographic,
      psychologic, and medical characteristics, attitudes, and quality of life of users
      and nonusers of CT. PATIENTS AND METHODS: Questionnaires were administered to
      1,027 patients attending ambulatory and inpatient hematology or oncology
      facilities at three hospitals. Medical information was extracted from charts.
      Univariate and multivariate comparisons of users and nonusers of CT were
      performed. RESULTS: A total of 526 participants (51.2%) had used CT since their
      diagnosis, and 357 patients (34.9%) had used CT recently (in the past 3 months).
      Factors that multivariate analysis found to be significantly associated (P <.05)
      with recent CT use were as follows: female sex; age 35 to 59 years; more
      education; coming to the hospital by private car; advanced disease status; having
      a close friend or a relative with cancer; and attending support groups or
      individual counseling. After controlling for these factors, individually examined
      psychosocial variables associated with recent CT use included the following (odds
      ratios [OR] with 95% confidence intervals [CI]): needs unmet by conventional
      medicine (OR, 2.76; 95% CI, 1.95 to 3.89); helplessness (OR, 1.39; 95% CI, 1.0 to
      1.91); incomplete trust in the doctor (OR, 1.49; 95% CI, 1.08 to 2.06); and
      changed outlook or beliefs since the diagnosis of cancer (OR, 1.47; 95% CI, 1.07
      to 2.02). Functional quality of life (including physical, emotional, social, and
      role function) and symptom (fatigue and diarrhea) scores were significantly worse
      for recent CT users compared with nonusers, controlling for age, sex, and current
      disease status. CONCLUSION: Characteristics associated with CT use include age,
      sex, education, and advanced disease. Significant associations between CT use and
      attending supportive psychotherapy, unmet needs, helplessness, and worse
      emotional and social function indicate considerable distress, suggesting that
      increased attention to psychosocial needs within oncologic settings is warranted.

PMID- 11331324
TI  - Safety and efficacy of temozolomide in patients with recurrent anaplastic
      oligodendrogliomas after standard radiotherapy and chemotherapy.
AB  - PURPOSE: Most primary oligodendrogliomas and mixed gliomas (oligoastrocytoma)
      respond to treatment with procarbazine, lomustine, and vincristine (PCV), with
      response rates of approximately 80%. However, limited data on second-line
      treatments are available in patients with recurrent tumors. A novel second
      generation alkylating agent, temozolomide, has recently demonstrated efficacy and
      safety in patients with recurrent glioblastoma multiforme and anaplastic
      astrocytoma. This study describes the effects of temozolomide in patients with
      recurrent anaplastic oligodendroglioma (AO) and anaplastic mixed oligoastrocytoma
      (AOA). PATIENTS AND METHODS: Forty-eight patients with histologically confirmed
      AO or AOA who had received previous PCV chemotherapy were treated with
      temozolomide (150 to 200 mg/m2/d for 5 days per 28-day cycle). The primary end
      point was objective response. Secondary end points included progression-free
      survival (PFS), time to progression, overall survival (OS), safety, and
      tolerability. RESULTS: Eight patients (16.7%) experienced a complete response, 13
      patients (27.1%) experienced a partial response (objective response rate, 43.8%),
      and 19 patients (39.6%) experienced stable disease. For the entire treatment
      group, median PFS was 6.7 months and median OS was 10 months. For objective
      responders, median PFS was 13.1 months and median OS was 16 months. For complete
      responders, PFS was more than 11. 8 months and OS was more than 26 months.
      Response correlated with improved survival. Temozolomide was safe and well
      tolerated. Twelve patients developed grade 1/2 thrombocytopenia and three
      patients developed grade 3/4 thrombocytopenia. CONCLUSION: Temozolomide is safe
      and effective in the treatment of recurrent AO and AOA.

PMID- 11331325
TI  - Bexarotene is effective and safe for treatment of refractory advanced-stage
      cutaneous T-cell lymphoma: multinational phase II-III trial results.
AB  - PURPOSE: Cutaneous T-cell lymphomas (CTCL) are malignancies of T cells appearing
      as skin lesions and are responsive to retinoid therapy. Safety and efficacy of a
      novel RXR-selective retinoid (rexinoid) bexarotene (Targretin, LGD1069; Ligand
      Pharmaceuticals Inc, San Diego, CA) was evaluated as a single-agent oral therapy
      administered once daily in an open-label study in patients with refractory
      advanced-stage CTCL. PATIENTS AND METHODS: Ninety-four patients with biopsy
      confirmed CTCL in advanced stages (IIB-IVB) were enrolled at 26 centers. Fifty
      six patients received an initial dose of 300 mg/m2/d oral bexarotene and 38
      started at more than 300 mg/m2/d. RESULTS: Clinical complete and partial
      responses were reported by Primary End point Classification for the study in 45%
      (25 of 56) of patients enrolled at 300 mg/m2/d dosing. At more than 300 mg/m2/d,
      55% (21 of 38) of patients responded, including 13% (five of 38) clinical
      complete. For the 300 mg/m2/d initial dose group, the rate of relapse after
      response was 36% and the projected median duration of response was 299 days.
      Improvements were also seen in overall body-surface area involvement, median
      index lesion surface area, adenopathy, cutaneous tumors, pruritus, and CTCL
      specific quality of life. The most frequent drug-related adverse events included
      hypertriglyceridemia (associated rarely with pancreatitis), hypercholesterolemia,
      hypothyroidism, and headache. CONCLUSION: Bexarotene is the first in a novel
      class of pharmacologic agents, the RXR-selective retinoids, or rexinoids.
      Bexarotene is orally administered, safe, and generally well tolerated with
      reversible side effects, and is effective for the treatment of advanced,
      refractory CTCL.

PMID- 11331326
TI  - Detection of chromosome abnormalities pre-high-dose treatment in patients
      developing therapy-related myelodysplasia and secondary acute myelogenous
      leukemia after treatment for non-Hodgkin's lymphoma.
AB  - PURPOSE: To assess whether pre-high-dose therapy (HDT)-related factors play a
      critical role in the development of therapy-related myelodysplasia (tMDS) or
      secondary acute myelogenous leukemia (sAML). PATIENTS AND METHODS: Twenty-nine of
      230 patients with a primary diagnosis of non-Hodgkin's lymphoma (NHL) developed
      tMDS/sAML after HDT comprising cyclophosphamide and total-body irradiation (TBI)
      supported by autologous hematopoietic progenitor cells. G-banding and
      fluorescence in-situ hybridization (FISH) were used to detect clonal cytogenetic
      abnormalities. RESULTS: The majority of patients showed complex karyotypes at
      diagnosis of tMDS/sAML containing, in particular, complete or partial loss of
      chromosomes 5 and/or 7. Using single locus-specific FISH probes, significant
      levels of clonally abnormal cells were found before HDT in 20 of 20 tMDS/sAML
      patients screened, compared with three of 24 patients screened who currently have
      not developed tMDS/sAML, at a median follow-up of 5.9 years after HDT.
      CONCLUSION: Prior cytotoxic therapy may play an important etiologic role and may
      predispose to the development of tMDS/sAML. Using a triple FISH assay designed to
      detect loss of chromosomal material from 5q31, 7q22, or 13q14, significant levels
      of abnormal cells can be detected before HDT and may predict which patients are
      at increased risk of developing secondary disease. Further prospective evaluation
      of this FISH assay is warranted to determine its predictive power in this
      setting.

PMID- 11331327
TI  - Comparison of cytogenetic and molecular genetic detection of t(8;21) and inv(16)
      in a prospective series of adults with de novo acute myeloid leukemia: a Cancer
      and Leukemia Group B Study.
AB  - PURPOSE: To prospectively compare cytogenetics and reverse transcriptase
      polymerase chain reaction (RT-PCR) for detection of t(8;21)(q22;q22) and
      inv(16)(p13q22)/t(16;16)(p13;q22), aberrations characteristic of core-binding
      factor (CBF) acute myeloid leukemia (AML), in 284 adults newly diagnosed with
      primary AML. PATIENTS AND METHODS: Cytogenetic analyses were performed at local
      laboratories, with results reviewed centrally. RT-PCR for AML1/ETO and
      CBFbeta/MYH11 was performed centrally. RESULTS: CBF AML was ultimately identified
      in 48 patients: 21 had t(8;21) or its variant and AML1/ETO, and 27 had
      inv(16)/t(16;16), CBFbeta/MYH11, or both. Initial cytogenetic and RT-PCR analyses
      correctly classified 95.7% and 96.1% of patients, respectively (P =.83). Initial
      cytogenetic results were considered to be false-negative in three AML1/ETO
      positive patients with unique variants of t(8;21), and in three CBFbeta/MYH11
      positive patients with, respectively, an isolated +22; del(16)(q22),+22; and a
      normal karyotype. The latter three patients were later confirmed to have
      inv(16)/t(16;16) cytogenetically. Only one of 124 patients reported initially as
      cytogenetically normal was ultimately RT-PCR-positive. There was no false
      positive cytogenetic result. Initial RT-PCR was falsely negative in two patients
      with inv(16) and falsely positive for AML1/ETO in two and for CBFbeta/MYH11 in
      another two patients. Two patients with del(16)(q22) were found to be
      CBFbeta/MYH11-negative. M4Eo marrow morphology was a good predictor of the
      presence of inv(16)/t(16;16). CONCLUSION: Patients with t(8;21) or inv(16) can be
      successfully identified in prospective multi-institutional clinical trials. Both
      cytogenetics and RT-PCR detect most such patients, although each method has
      limitations. RT-PCR is required when the cytogenetic study fails; it is also
      required to determine whether patients with suspected variants of t(8;21),
      del(16)(q22), or +22 represent CBF AML. RT-PCR should not replace cytogenetics
      and should not be used as the only diagnostic test for detection of CBF AML
      because of the possibility of obtaining false-positive or false-negative results.

PMID- 11331328
TI  - Phase I and pharmacokinetic study of BMS-184476, a taxane with greater potency
      and solubility than paclitaxel.
AB  - PURPOSE: To assess the feasibility, toxicity, pharmacokinetics, and preliminary
      activity of BMS-184476 administered as a 1-hour intravenous (IV) infusion every 3
      weeks. PATIENTS AND METHODS: Patients with advanced solid malignancies were
      treated with escalating doses of BMS-184476 as a 1-hour IV infusion every 3 weeks
      without premedication to prevent hypersensitivity reactions (HSR). Plasma
      sampling and urine collections were performed to characterize the
      pharmacokinetics and pharmacodynamics of BMS-184474. RESULTS: Thirty-four
      patients were treated with 78 courses of BMS-184476 at five dose levels ranging
      from 20 to 80 mg/m2. Dose-limiting toxicity (DLT), consisting of severe
      neutropenia with fever, severe diarrhea, and/or severe mucositis, was experienced
      during course 1 by six of nine minimally pretreated patients treated at the 70
      and 80 mg/m2 dose level. In contrast, of 15 assessable patients treated at the 60
      mg/m2 dose level, which is the maximum-tolerated dose (MTD) of BMS-184476 on this
      administration schedule, only one heavily pretreated patient developed DLT (grade
      4 neutropenia with fever and grade 3 diarrhea). One patient developed a grade 2
      HSR during a second course of BMS-184476 at the 40 mg/m2 dose level. A previously
      untreated patient with an advanced cholangiocarcinoma experienced a partial
      response, and a patient with an untreated carcinoma of the gastroesophageal
      junction had a minor response. The pharmacokinetics of BMS-184476 seemed linear
      in the dose range studied. Mean +/- SD values for clearance, volume of
      distribution at steady-state, and terminal half-life were 220 +/- 89 mL/min/m2,
      402 +/- 231 L/m2, and 40.8 +/- 21.8 hours, respectively. CONCLUSION: The MTD and
      recommended dose for phase II evaluations of BMS-184476 is 60 mg/m2 as a 1-hour
      IV infusion every 3 weeks. The results of this study suggest that BMS-184476 may
      have several advantages compared with paclitaxel in terms of toxicity,
      pharmacokinetics, pharmaceutics, and administration and warrants further clinical
      development.

PMID- 11331329
TI  - Impact of fluorine-18 fluorodeoxyglucose positron emission tomography on patient
      management: first year's experience in a clinical center.
AB  - PURPOSE: To measure the impact of whole-body fluorodeoxyglucose (FDG) positron
      emission tomography (PET) on patient management during its first year of use in a
      community hospital. MATERIALS AND METHODS: First-year FDG-PET impact was
      determined from 463 referring physicians' evaluations of their patients' PET
      imaging results using two surveys. Survey 1 was given to all physicians referring
      patients to PET to discover whether PET changed patient management or had
      decision-making value in the patient's clinical algorithm. Survey 2 was given to
      one surgeon and one pulmonologist after therapy to determine how PET affected the
      surgical, chemotherapeutic, and/or radiotherapeutic treatment for the 53 cancer
      patients they referred. RESULTS: The 463 responses to survey 1 described 23
      different PET indications. Lung (40%), head and neck (18%), and colorectal
      cancers (11%) were the three leading causes of referral. PET changed patient
      management/therapy in 45% of all patients referred and had inferential/decision
      making value in another 44%. Overall, PET had some type of positive influence in
      412 (89%) of the patients. Survey 2 provided a more detailed assessment of 53
      referrals from two specialists. PET positively affected surgery in 31 patients
      (58%), prompted the addition of chemotherapy or radiation therapy in nine
      patients (17%), and eliminated chemotherapy or radiation therapy in four cases
      (8%). Overall, PET affected patient management/therapy in 70% of the cases and
      had some decision-making value in another 26%, for a combined PET impact on
      patient management of 96%. CONCLUSION: FDG-PET can be valuable for physicians in
      clinical practice. Its sensitivity and specificity in metabolic imaging, when
      combined with complementary anatomic imaging techniques, contribute significantly
      to the clinical treatment of cancer patients. In addition, the high accuracy of
      FDG-PET makes it a cost-effective radiologic procedure in the work-up of all
      suspected and/or recurrent cancer patients. Further research is needed to link
      this demonstrated impact on patient management to cost-effectiveness.

PMID- 11331330
TI  - Phase II study of docetaxel, estramustine, and low-dose hydrocortisone in men
      with hormone-refractory prostate cancer: a final report of CALGB 9780. Cancer and
      Leukemia Group B.
AB  - PURPOSE: To investigate the combination of docetaxel, estramustine (EM), and low
      dose hydrocortisone in men with hormone-refractory prostate cancer (HRPC).
      PATIENTS AND METHODS: Combinations of EM with other antimitotic agents such as
      docetaxel are synergistic in vitro and show significant clinical activity in
      patients with HRPC. We studied intravenous administration of docetaxel 70
      mg/m(2), oral estramustine, and low-dose daily hydrocortisone in men with HRPC
      who demonstrated progression after initial hormone therapy. RESULTS: Of the 47
      men enrolled onto this multicenter cooperative group study, 46 were assessable
      for response and/or toxicity. In the 24 patients with measurable disease, there
      were three complete and nine partial responses for a measurable disease response
      rate of 50% (12 of 24 patients; 95% confidence interval [CI], 27% to 73%). In the
      44 patients in whom pretreatment prostate-specific antigen (PSA) was elevated, 30
      (68%) had a 50% or greater decrease, and 25 (57%) had a 75% or greater decrease
      in PSA. The combined measurable disease and biochemical response rate in all 46
      assessable patients was 54% (three complete responses, 22 partial responses, 95%
      CI, 37% to 71%). The predominant toxicity was neutropenia, with 26% of patients
      having grade 3 and 30% having grade 4 granulocytopenia; there were no episodes of
      febrile neutropenia. Other common but mild adverse effects included
      malaise/fatigue, peripheral edema, and hyperglycemia. The incidence of
      thromboembolic events during therapy was 9%. With a median follow-up of 17
      months, the median survival was 20 months. The median time to disease progression
      was 8 months for all patients, and 10 months for those with measurable disease.
      CONCLUSION: This therapy is efficacious and moderately well tolerated in HRPC and
      should be compared in a phase III trial with mitoxantrone and prednisone.

PMID- 11331331
TI  - Health outcomes after external-beam radiation therapy for clinically localized
      prostate cancer: results from the Prostate Cancer Outcomes Study.
AB  - PURPOSE: Studies reporting effects of radiotherapy for prostate cancer on sexual,
      bowel, and urinary function have been conducted primarily in referral centers or
      academic institutions. Effects of external-beam radiotherapy for prostate cancer
      among a population-based cohort were assessed. PATIENTS AND METHODS: The study
      population included 497 white, Hispanic, and African-American men with localized
      prostate cancer from six US cancer registries who were diagnosed between October
      1, 1994, and October 31, 1995, and treated initially with external-beam
      radiotherapy. They were interviewed at regular intervals, and medical records
      were reviewed. Distributions of responses for bowel-, urinary-, and sexual
      related functions at 6, 12, and 24 months after diagnosis and adjusted mean
      composite change scores for each domain were analyzed. RESULTS: Declines of 28.9%
      in the sexual function score and 5.4% in the bowel function score occurred by 24
      months, whereas at this time, the urinary function score was relatively
      unchanged. A total of 43% of those who were potent before diagnosis became
      impotent after 24 months. More than two thirds of the men were satisfied with
      their treatment and would make the same decision again. CONCLUSION: Sexual
      function was the most adversely affected quality-of-life domain, with problems
      continuing to increase between 12 and 24 months. Bowel function problems
      increased at 6 months, with partial resolution observed by 24 months. Despite the
      side effects, satisfaction with therapy was high. These results are
      representative of men in community practice settings and may be of assistance to
      men and to clinicians when making treatment decisions.

PMID- 11331332
TI  - Combination paclitaxel, carboplatin, and gemcitabine is an active treatment for
      advanced urothelial cancer.
AB  - PURPOSE: To determine the efficacy and toxicity of the drug combination of
      carboplatin, paclitaxel, and gemcitabine in patients with advanced urothelial
      carcinoma. PATIENTS AND METHODS: Patients eligible included those with advanced
      urothelial malignancy of any histology, no previous chemotherapy for metastatic
      disease, Southwest Oncology Group performance status of 2 or less, serum
      creatinine levels of 2 mg/dL or less, and adequate bone marrow and hepatic
      function. Treatment consisted of paclitaxel 200 mg/m2, carboplatin (target area
      under the curve = 5) on day 1, and gemcitabine 800 mg/m2 on days 1 and 8,
      repeated every 21 days. RESULTS: Forty-nine patients (44 men and five women) were
      enrolled; the patients' median age was 63 years, and their median creatinine
      clearance was 78 mL/min (range, 26 to 165 mL/min). Forty-three patients had
      transitional cell carcinoma, and six had squamous cell carcinoma or mixed
      histology. Ten patients had metastases to lymph nodes only, six had locally
      advanced disease, four had locally recurrent disease, 24 patients had visceral
      metastases, and five had soft tissue metastases. Twenty-one patients had disease
      in one site, 16 in two sites, and 12 in three sites. A total of 272 cycles were
      administered (median, six cycles; range, 1 to 15 cycles). Major toxicities were
      grade 3 and 4 neutropenia in 17 and 19 patients, respectively; grade 3 and 4
      thrombocytopenia in 15 and six patients, respectively; grade 3 and 4 anemia in 10
      and two patients, respectively; grade 3 neuropathy in four patients; and diarrhea
      in two patients. The incidence of febrile neutropenia was 1.4%; no patients died
      of drug toxicity. Forty-seven of the 49 patients were assessable for response.
      Fifteen (32%) patients experienced a complete response, and 17 (36%) patients
      experienced a partial response (32 of 47 patients, 68%; 95% confidence interval,
      56.27 to 82.86). Responses were seen in all sites, including 15 (68%) of 22
      patients with visceral metastases. The median survival was 14.7 months, with a 1
      year survival of 59%. CONCLUSION: Combination paclitaxel, carboplatin, and
      gemcitabine is active; an encouraging number of patients with advanced urothelial
      carcinoma treated with this regimen experienced complete remission.

PMID- 11331333
TI  - Predicting outcome to chemotherapy in patients with germ cell tumors: the value
      of the rate of decline of human chorionic gonadotrophin and alpha-fetoprotein
      during therapy.
AB  - PURPOSE: The prognostic significance of the rate of decline of the serum tumor
      marker alpha-fetoprotein (AFP) and human chorionic gonadotrophin (HCG) during the
      first two cycles of chemotherapy in germ cell tumor (GCT) patients was initially
      reported by us, but its value has been debated. We re-examined this issue in the
      context of the International Germ Cell Cancer Collaborative Group (IGCCCG) risk
      classification system and investigated the role of including in the analysis
      patients whose markers normalized early. PATIENTS AND METHODS: One hundred eighty
      nine GCT patients with elevated AFP/HCG marker values treated with platinum-based
      chemotherapy between 1986 and 1998 were included in this analysis. Patients were
      classified as good, intermediate, or poor risk by the IGCCCG criteria and as
      having satisfactory or unsatisfactory marker decline. Risk and marker decline
      were correlated with response, event-free survival, and overall survival.
      RESULTS: Satisfactory marker decline predicted improved complete response (CR)
      proportion and event-free and overall survival (P <.0001). The CR proportion, 2
      year event-free, and 2-year overall survival rates for patients with a
      satisfactory and unsatisfactory marker decline were 92% versus 62%, 91% versus
      69%, and 95% versus 72%, respectively. Marker decline remained a significant
      variable for all three end points when adjusted for risk (P <.01) with the
      outcome differences most pronounced in the poor-risk group. CONCLUSION: The rate
      of marker decline during chemotherapy has prognostic value independent of risk
      and may play a significant role in the management of poor-risk patients. It is
      appropriate to include patients whose markers normalized early.

PMID- 11331334
TI  - Strategies to manage the adverse effects of oral morphine: an evidence-based
      report.
AB  - Successful pain management with opioids requires that adequate analgesia be
      achieved without excessive adverse effects. By these criteria, a substantial
      minority of patients treated with oral morphine (10% to 30%) do not have a
      successful outcome because of (1) excessive adverse effects, (2) inadequate
      analgesia, or (3) a combination of both excessive adverse effects along with
      inadequate analgesia. The management of excessive adverse effects remains a major
      clinical challenge. Multiple approaches have been described to address this
      problem. The clinical challenge of selecting the best option is enhanced by the
      lack of definitive, evidence-based comparative data. Indeed, this aspect of
      opioid therapeutics has become a focus of substantial controversy. This study
      presents evidence-based recommendations for clinical-practice formulated by an
      Expert Working Group of the European Association of Palliative Care (EAPC)
      Research NETWORK: These recommendations highlight the need for careful evaluation
      to distinguish between morphine adverse effects from comorbidity, dehydration, or
      drug interactions, and initial consideration of dose reduction (possibly by the
      addition of a co analgesic). If side effects persist, the clinician should
      consider options of symptomatic management of the adverse effect, opioid
      rotation, or switching route of systemic administration. The approaches are
      described and guidelines are provided to aid in selecting between therapeutic
      options.

PMID- 11331335
TI  - BRCA1/2 testing: complex themes in result interpretation.
AB  - Since the cloning of BRCA1 and BRCA2, genetic testing for breast and ovarian
      cancer susceptibility has become more widespread. However, interpretation of test
      results is not always straightforward. To illustrate this point, five vignettes
      adapted from actual cases are presented. As these cases demonstrate, in many high
      risk families, a deleterious mutation in BRCA1 or BRCA2 is not identified in an
      affected proband. There are several potential explanations for such a finding,
      namely that an undetected mutation in BRCA1 or BRCA2 may exist, or there could be
      a mutation in a rare or undiscovered gene. In addition, the possibility that
      women with breast cancer represent sporadic cases within hereditary cancer
      families must also be considered. Finally, the occurrence of BRCA1/2 variants of
      uncertain significance, often missense mutations, further complicates the risk
      assessment. In some of these instances, extending testing to relatives can be
      helpful to clarify results. When hereditary breast cancer cannot be ruled out,
      individuals may still be at increased risk for cancer and therefore need to
      obtain appropriate surveillance. The process of genetic counseling is critical
      both before and after testing to ensure that patients understand the potential
      medical and psychosocial implications of testing and are aware of available
      options and resources. A multidisciplinary approach to service delivery, which
      includes clinicians in genetics and oncology, can facilitate patients' decision
      making and provide continued access to information and support.

PMID- 11331336
TI  - An online educational facility for medical oncology trainees: www.vmotg.org.
AB  - PURPOSE: To design, implement, and evaluate a comprehensive educational Web site
      for medical oncology trainees. METHODS: The Web site was designed with three main
      areas (termed Journal Club, Key Papers, and Oncology Links) and compiled from
      articles presented at the Victorian Medical Oncology Trainees' Group journal club
      from the preceding 3 years. The Key Papers section was then reviewed by 30
      academic medical oncologists. The site was advertised by mail and at the Annual
      Meeting of the Medical Oncology Group of Australia. Evaluation was by mail
      survey. RESULTS: The Web site, which may be accessed at www.vmotg.org, comprises
      more than 170 pages and 30,000 words of text. Journal club sessions are
      summarized with presented articles linked to abstracts from PubMed. Key Papers
      lists from five to 25 pivotal articles in each of 35 categories. Oncology Links
      is an extensive list of links in 10 categories including organizations, journals,
      and practice guidelines. Twenty-six of 45 trainees and 82 of 190 oncologists
      responded to the survey. Eighty-one percent of these trainees and 28% of
      oncologists have used the Web site. Ninety-six percent consider the Web site easy
      to use and "a useful medical oncology resource." All trainees rated the site good
      to excellent in terms of relevance and 94% considered the site beneficial to
      their education. CONCLUSION: The Web site www.vmotg.org is a relevant and useful
      educational resource for Australian medical oncology trainees and oncologists. As
      far as the authors are aware, this is the only educational site specifically for
      medical oncology trainees throughout the world. It may be a valuable oncology
      education resource for trainees in other countries, particularly those in
      isolated areas.

PMID- 11331337
TI  - Unusual aspects of breast cancer: case 1. Angiosarcoma of the breast.

PMID- 11331338
TI  - Unusual aspects of breast cancer: case 2. Synchronous bilateral lung and breast
      cancers.

PMID- 11331339
TI  - Unusual aspects of breast cancer: case 3. Blue hives during lymphatic mapping for
      breast cancer.

PMID- 11331340
TI  - Giving bad news to cancer patients: matching process and content.

PMID- 11331341
TI  - Is anastrozole superior to tamoxifen as first-line therapy for advanced breast
      cancer?

PMID- 11331342
TI  - Is anastrozole superior to tamoxifen as first-line therapy for advanced breast
      cancer?

PMID- 11331343
TI  - Is anastrozole superior to tamoxifen as first-line therapy for advanced breast
      cancer?

PMID- 11331344
TI  - Is anastrozole superior to tamoxifen as first-line therapy for advanced breast
      cancer?

PMID- 11331346
TI  - Is anastrozole superior to tamoxifen as first-line therapy for advanced breast
      cancer?

PMID- 11331347
TI  - Affinity and location of an internal K+ ion binding site in shaker K channels.
AB  - We have examined the interaction between TEA and K+ ions in the pore of Shaker
      potassium channels. We found that the ability of external TEA to antagonize block
      of Shaker channels by internal TEA depended on internal K+ ions. In contrast,
      this antagonism was independent of external K+ concentrations between 0.2 and 40
      mM. The external TEA antagonism of internal TEA block increased linearly with the
      concentration of internal K+ ions. In addition, block by external TEA was
      significantly enhanced by increases in the internal K+ concentration. These
      results suggested that external TEA ions do not directly antagonize internal TEA,
      but rather promote increased occupancy of an internal K+ site by inhibiting the
      emptying of that site to the external side of the pore. We found this mechanism
      to be quantitatively consistent with the results and revealed an intrinsic
      affinity of the site for K+ ions near 65 mM located approximately 7% into the
      membrane electric field from the internal end of the pore. We also found that the
      voltage dependence of block by internal TEA was influenced by internal K+ ions.
      The TEA site (at 0 internal K+) appeared to sense approximately 5% of the field
      from the internal end of the pore (essentially colocalized with the internal K+
      site). These results lead to a refined picture of the number and location of ion
      binding sites at the inner end of the pore in Shaker K channels.

PMID- 11331348
TI  - Ryanoid modification of the cardiac muscle ryanodine receptor channel results in
      relocation of the tetraethylammonium binding site.
AB  - The interaction of ryanodine and derivatives of ryanodine with the high affinity
      binding site on the ryanodine receptor (RyR) channel brings about a
      characteristic modification of channel function. In all cases, channel open
      probability increases dramatically and single-channel current amplitude is
      reduced. The amplitude of the ryanoid-modified conductance state is determined by
      structural features of the ligand. An investigation of ion handling in the
      ryanodine-modified conductance state has established that reduced conductance
      results from changes in both the affinity of the channel for permeant ions and
      the relative permeability of ions within the channel (Lindsay, A.R.G., A. Tinker,
      and A.J. Williams. 1994. J. Gen. Physiol. 104:425-447). It has been proposed that
      these alterations result from a reorganization of channel structure induced by
      the binding of the ryanoid. The experiments reported here provide direct evidence
      for ryanoid-induced restructuring of RyR. TEA+ is a concentration- and voltage
      dependent blocker of RyR in the absence of ryanoids. We have investigated block
      of K+ current by TEA+ in the unmodified open state and modified conductance
      states of RyR induced by 21-amino-9alpha-hydroxyryanodine, 21-azido-9alpha
      hydroxyryanodine, ryanodol, and 21-p-nitrobenzoylamino-9alpha-hydroxyryanodine.
      Analysis of the voltage dependence of block indicates that the interaction of
      ryanoids with RyR leads to an alteration in this parameter with an apparent
      relocation of the TEA+ blocking site within the voltage drop across the channel
      and an alteration in the affinity of the channel for the blocker. The degree of
      change of these parameters correlates broadly with the change in conductance of
      permeant cations induced by the ryanoids, indicating that modification of RyR
      channel structure by ryanoids is likely to underlie both phenomena.

PMID- 11331349
TI  - Kinetics of inward-rectifier K+ channel block by quaternary alkylammonium ions.
      dimension and properties of the inner pore.
AB  - We examined block of two inward-rectifier K+ channels, IRK1 and ROMK1, by a
      series of intracellular symmetric quaternary alkylammonium ions (QAs) whose side
      chains contain one to five methylene groups. As shown previously, the ROMK1
      channels bind larger QAs with higher affinity. In contrast, the IRK1 channels
      strongly select TEA over smaller or larger QAs. This remarkable difference in QA
      selectivity between the two channels results primarily from differing QA
      unbinding kinetics. The apparent rate constant for binding (kon) of all examined
      QAs is significantly smaller than expected for a diffusion-limited process.
      Furthermore, a large ( approximately 30-fold) drop in kon occurs when the number
      of methylene groups in QAs increases from three to four. These observations argue
      that between the intracellular solution and the QA-binding locus, there exists a
      constricted pathway, whose dimension ( approximately 9 A) is comparable to that
      of a K+ ion with a single H2O shell.

PMID- 11331350
TI  - Substrate and product dependence of force and shortening in fast and slow smooth
      muscle.
AB  - To explore the molecular mechanisms responsible for the variation in smooth
      muscle contractile kinetics, the influence of MgATP, MgADP, and inorganic
      phosphate (P(i)) on force and shortening velocity in thiophosphorylated "fast"
      (taenia coli: maximal shortening velocity Vmax = 0.11 ML/s) and "slow" (aorta:
      Vmax = 0.015 ML/s) smooth muscle from the guinea pig were compared. P(i)
      inhibited active force with minor effects on the V(max). In the taenia coli, 20
      mM P(i) inhibited force by 25%. In the aorta, the effect was markedly less (<
      10%), suggesting differences between fast and slow smooth muscles in the binding
      of P(i) or in the relative population of P(i) binding states during cycling.
      Lowering of MgATP reduced force and V(max). The aorta was less sensitive to
      reduction in MgATP (Km for Vmax: 80 microM) than the taenia coli (Km for Vmax:
      350 microM). Thus, velocity is controlled by steps preceding the ATP binding and
      cross-bridge dissociation, and a weaker binding of ATP is not responsible for the
      lower V(max) in the slow muscle. MgADP inhibited force and V(max). Saturating
      concentrations of ADP did not completely inhibit maximal shortening velocity. The
      effect of ADP on Vmax was observed at lower concentrations in the aorta compared
      with the taenia coli, suggesting that the ADP binding to phosphorylated and
      cycling cross-bridges is stronger in slow compared with fast smooth muscle.

PMID- 11331351
TI  - Airway surface liquid: end of the controversy?

PMID- 11331352
TI  - Airway surface liquid osmolality measured using fluorophore-encapsulated
      liposomes.
AB  - The airway surface liquid (ASL) is the thin layer of fluid coating the luminal
      surface of airway epithelial cells at an air interface. Its composition and
      osmolality are thought to be important in normal airway physiology and in airway
      diseases such as asthma and cystic fibrosis. The determinants of ASL osmolality
      include epithelial cell solute and water transport properties, evaporative water
      loss, and the composition of secreted fluids. We developed a noninvasive approach
      to measure ASL osmolality using osmotically sensitive 400-nm-diam liposomes
      composed of phosphatidylcholine/cholesterol/polyethylene glycol
      phosphatidylcholine (1:0.3:0.08 molar ratio). Calcein was encapsulated in the
      liposomes at self-quenching concentrations (30 mM) as a volume-sensitive marker,
      together with sulforhodamine 101 (2 mM) as a volume-insensitive reference.
      Liposome calcein/sulforhodamine 101 fluorescence ratios responded rapidly (< 0.2
      s) and stably to changes in solution osmolality. ASL osmolality was determined
      from calcein/sulforhodamine 101 fluorescence ratios after addition of microliter
      quantities of liposome suspensions to the ASL. In bovine airway epithelial cells
      cultured on porous supports at an air-liquid interface, ASL thickness (by
      confocal microscopy) was 22 microm and osmolality was 325 +/- 12 mOsm. In
      anesthetized mice in which a transparent window was created in the trachea, ASL
      thickness was 55 microm and osmolality was 330 +/- 36 mOsm. ASL osmolality was
      not affected by pharmacological inhibition of CFTR in airway cell cultures or by
      genetic deletion of CFTR in knockout mice. ASL osmolality could be increased
      substantially to > 400 mOsm by exposure of the epithelium to dry air; the data
      were modeled mathematically using measured rates of osmosis and evaporative water
      loss. These results establish a ratio imaging method to map osmolality in
      biological compartments. ASL fluid is approximately isosmolar under normal
      physiological conditions, but can become hyperosmolar when exposed to dry air,
      which may induce cough and airway reactivity in some patients.

PMID- 11331353
TI  - Subtype-specific regulation of inositol 1,4,5-trisphosphate receptors:
      controlling calcium signals in time and space.

PMID- 11331354
TI  - Regulation by Ca2+ and inositol 1,4,5-trisphosphate (InsP3) of single recombinant
      type 3 InsP3 receptor channels. Ca2+ activation uniquely distinguishes types 1
      and 3 insp3 receptors.
AB  - The inositol 1,4,5-trisphosphate (InsP(3)) receptor (InsP3R) is an endoplasmic
      reticulum-localized Ca2+ -release channel that controls complex cytoplasmic
      Ca(2+) signaling in many cell types. At least three InsP3Rs encoded by different
      genes have been identified in mammalian cells, with different primary sequences,
      subcellular locations, variable ratios of expression, and heteromultimer
      formation. To examine regulation of channel gating of the type 3 isoform,
      recombinant rat type 3 InsP3R (r-InsP3R-3) was expressed in Xenopus oocytes, and
      single-channel recordings were obtained by patch-clamp electrophysiology of the
      outer nuclear membrane. Gating of the r-InsP3R-3 exhibited a biphasic dependence
      on cytoplasmic free Ca2+ concentration ([Ca2+]i). In the presence of 0.5 mM
      cytoplasmic free ATP, r-InsP3R-3 gating was inhibited by high [Ca2+]i with
      features similar to those of the endogenous Xenopus type 1 Ins3R (X-InsP3R-1).
      Ca2+ inhibition of channel gating had an inhibitory Hill coefficient of
      approximately 3 and half-maximal inhibiting [Ca2+]i (Kinh) = 39 microM under
      saturating (10 microM) cytoplasmic InsP3 concentrations ([InsP3]). At [InsP3] <
      100 nM, the r-InsP3R-3 became more sensitive to Ca2+ inhibition, with the InsP(3)
      concentration dependence of Kinh described by a half-maximal [InsP3] of 55 nM and
      a Hill coefficient of approximately 4. InsP(3) activated the type 3 channel by
      tuning the efficacy of Ca2+ to inhibit it, by a mechanism similar to that
      observed for the type 1 isoform. In contrast, the r-InsP3R-3 channel was uniquely
      distinguished from the X-InsP3R-1 channel by its enhanced Ca2+ sensitivity of
      activation (half-maximal activating [Ca2+]i of 77 nM instead of 190 nM) and lack
      of cooperativity between Ca2+ activation sites (activating Hill coefficient of 1
      instead of 2). These differences endow the InsP3R-3 with high gain InsP3-induced
      Ca2+ release and low gain Ca2+ -induced Ca2+ release properties complementary to
      those of InsP3R-1. Thus, distinct Ca2+ signals may be conferred by complementary
      Ca2+ activation properties of different InsP3R isoforms.

PMID- 11331355
TI  - ATP regulation of recombinant type 3 inositol 1,4,5-trisphosphate receptor
      gating.
AB  - A family of inositol 1,4,5-trisphosphate (InsP3) receptor (InsP3R) Ca2+ release
      channels plays a central role in Ca2+ signaling in most cells, but functional
      correlates of isoform diversity are unclear. Patch-clamp electrophysiology of
      endogenous type 1 (X-InsP3R-1) and recombinant rat type 3 InsP3R (r-InsP3R-3)
      channels in the outer membrane of isolated Xenopus oocyte nuclei indicated that
      enhanced affinity and reduced cooperativity of Ca2+ activation sites of the InsP3
      liganded type 3 channel distinguished the two isoforms. Because Ca2+ activation
      of type 1 channel was the target of regulation by cytoplasmic ATP free acid
      concentration ([ATP](i)), here we studied the effects of [ATP]i on the dependence
      of r-InsP(3)R-3 gating on cytoplasmic free Ca2+ concentration ([Ca2+]i. As [ATP]i
      was increased from 0 to 0.5 mM, maximum r-InsP3R-3 channel open probability (Po)
      remained unchanged, whereas the half-maximal activating [Ca2+]i and activation
      Hill coefficient both decreased continuously, from 800 to 77 nM and from 1.6 to
      1, respectively, and the half-maximal inhibitory [Ca2+]i was reduced from 115 to
      39 microM. These effects were largely due to effects of ATP on the mean closed
      channel duration. Whereas the r-InsP3R-3 had a substantially higher Po than X
      InsP3R-1 in activating [Ca2+]i (< 1 microM) and 0.5 mM ATP, the Ca2+ dependencies
      of channel gating of the two isoforms became remarkably similar in the absence of
      ATP. Our results suggest that ATP binding is responsible for conferring distinct
      gating properties on the two InsP3R channel isoforms. Possible molecular models
      to account for the distinct regulation by ATP of the Ca2+ activation properties
      of the two channel isoforms and the physiological implications of these results
      are discussed. Complex regulation by ATP of the types 1 and 3 InsP3R channel
      activities may enable cells to generate sophisticated patterns of Ca2+ signals
      with cytoplasmic ATP as one of the second messengers.

PMID- 11331356
TI  - PKC-mediated stimulation of amphibian CFTR depends on a single phosphorylation
      consensus site. insertion of this site confers PKC sensitivity to human CFTR.
AB  - Mutations of the CFTR, a phosphorylation-regulated Cl(-) channel, cause cystic
      fibrosis. Activation of CFTR by PKA stimulation appears to be mediated by a
      complex interaction between several consensus phosphorylation sites in the
      regulatory domain (R domain). None of these sites has a critical role in this
      process. Here, we show that although endogenous phosphorylation by PKC is
      required for the effect of PKA on CFTR, stimulation of PKC by itself has only a
      minor effect on human CFTR. In contrast, CFTR from the amphibians Necturus
      maculosus and Xenopus laevis (XCFTR) can be activated to similar degrees by
      stimulation of either PKA or PKC. Furthermore, the activation of XCFTR by PKC is
      independent of the net charge of the R domain, and mutagenesis experiments
      indicate that a single site (Thr665) is required for the activation of XCFTR.
      Human CFTR lacks the PKC phosphorylation consensus site that includes Thr665, but
      insertion of an equivalent site results in a large activation upon PKC
      stimulation. These observations establish the presence of a novel mechanism of
      activation of CFTR by phosphorylation of the R domain, i.e., activation by PKC
      requires a single consensus phosphorylation site and is unrelated to the net
      charge of the R domain.

PMID- 11331357
TI  - Histidine scanning mutagenesis of basic residues of the S4 segment of the shaker
      k+ channel.
AB  - The voltage sensor of the Shaker potassium channel is comprised mostly of
      positively charged residues in the putative fourth transmembrane segment, S4
      (Aggarwal, S.K., and R. MacKinnon. 1996. Neuron. 16:1169-1177; Seoh, S.-A., D.
      Sigg, D.M. Papazian, and F. Bezanilla. 1996. Neuron. 16:1159-1167). Movement of
      the voltage sensor in response to a change in the membrane potential was examined
      indirectly by measuring how the accessibilities of residues in and around the
      sensor change with voltage. Each basic residue in the S4 segment was individually
      replaced with a histidine. If the histidine tag is part of the voltage sensor,
      then the gating charge displaced by the voltage sensor will include the histidine
      charge. Accessibility of the histidine to the bulk solution was therefore
      monitored as pH-dependent changes in the gating currents evoked by membrane
      potential pulses. Histidine scanning mutagenesis has several advantages over
      other similar techniques. Since histidine accessibility is detected by labeling
      with solution protons, very confined local environments can be resolved and
      labeling introduces minimal interference of voltage sensor motion. After
      histidine replacement of either residue K374 or R377, there was no titration of
      the gating currents with internal or external pH, indicating that these residues
      do not move in the transmembrane electric field or that they are always
      inaccessible. Histidine replacement of residues R365, R368, and R371, on the
      other hand, showed that each of these residues traverses entirely from internal
      exposure at hyperpolarized potentials to external exposure at depolarized
      potentials. This translocation enables the histidine to transport protons across
      the membrane in the presence of a pH gradient. In the case of 371H,
      depolarization drives the histidine to a position that forms a proton pore.
      Kinetic models of titrateable voltage sensors that account for proton transport
      and conduction are presented. Finally, the results presented here are
      incorporated into existing information to propose a model of voltage sensor
      movement and structure.

PMID- 11331358
TI  - Properties of hyperpolarization-activated pacemaker current defined by coassembly
      of HCN1 and HCN2 subunits and basal modulation by cyclic nucleotide.
AB  - Members of the HCN channel family generate hyperpolarization-activated cation
      currents (Ih) that are directly regulated by cAMP and contribute to pacemaker
      activity in heart and brain. The four HCN isoforms show distinct but overlapping
      patterns of expression in different tissues. Here, we report that HCN1 and HCN2,
      isoforms coexpressed in neocortex and hippocampus that differ markedly in their
      biophysical properties, coassemble to generate heteromultimeric channels with
      novel properties. When expressed in Xenopus oocytes, HCN1 channels activate 5-10
      fold more rapidly than HCN2 channels. HCN1 channels also activate at voltages
      that are 10-20 mV more positive than those required to activate HCN2. In cell
      free patches, the steady-state activation curve of HCN1 channels shows a minimal
      shift in response to cAMP (+4 mV), whereas that of HCN2 channels shows a
      pronounced shift (+17 mV). Coexpression of HCN1 and HCN2 yields Ih currents that
      activate with kinetics and a voltage dependence that tend to be intermediate
      between those of HCN1 and HCN2 homomers, although the coexpressed channels do
      show a relatively large shift by cAMP (+14 mV). Neither the kinetics, steady
      state voltage dependence, nor cAMP dose-response curve for the coexpressed Ih can
      be reproduced by the linear sum of independent populations of HCN1 and HCN2
      homomers. These results are most simply explained by the formation of heteromeric
      channels with novel properties. The properties of these heteromeric channels
      closely resemble the properties of I(h) in hippocampal CA1 pyramidal neurons,
      cells that coexpress HCN1 and HCN2. Finally, differences in Ih channel properties
      recorded in cell-free patches versus intact oocytes are shown to be due, in part,
      to modulation of Ih by basal levels of cAMP in intact cells.

PMID- 11331360
TI  - Action potential bursting in subicular pyramidal neurons is driven by a calcium
      tail current.
AB  - Subiculum is the primary output area of the hippocampus and serves as a key relay
      center in the process of memory formation and retrieval. A majority of subicular
      pyramidal neurons communicate via bursts of action potentials, a mode of
      signaling that may enhance the fidelity of information transfer and synaptic
      plasticity or contribute to epilepsy when unchecked. In the present study, we
      show that a Ca(2+) tail current drives bursting in subicular pyramidal neurons.
      An action potential activates voltage-activated Ca(2+) channels, which deactivate
      slowly enough during action potential repolarization to produce an
      afterdepolarization that triggers subsequent action potentials in the burst. The
      Ca(2+) channels underlying bursting are located primarily near the soma, and the
      amplitude of Ca(2+) tail currents correlates with the strength of bursting across
      cells. Multiple channel subtypes contribute to Ca(2+) tail current, but the need
      for an action potential to produce the slow depolarization suggests a central
      role for high-voltage-activated Ca(2+) channels in subicular neuron bursting.

PMID- 11331359
TI  - p38 activation is required upstream of potassium current enhancement and caspase
      cleavage in thiol oxidant-induced neuronal apoptosis.
AB  - Oxidant-induced neuronal apoptosis has been shown to involve potassium and zinc
      dysregulation, energetic dysfunction, activation of stress-related kinases, and
      caspase cleavage. The temporal ordering and interdependence of these events was
      investigated in primary neuronal cultures exposed to the sulfhydryl oxidizing
      agent 2,2'-dithiodipyridine (DTDP), a compound that induces the intracellular
      release of zinc. We previously observed that tetraethylammonium (TEA), high
      extracellular potassium, or cysteine protease inhibitors block apoptosis induced
      by DTDP. We now report that both p38 and extracellular signal-regulated kinase
      phosphorylation are evident in neuronal cultures within 2 hr of a brief exposure
      to 100 microm DTDP. However, only p38 inhibition is capable of blocking oxidant
      induced toxicity. Cyclohexamide or actinomycin D does not attenuate DTDP-induced
      cell death, suggesting that posttranslational modification of existing targets,
      rather than transcriptional activation, is responsible for the deleterious
      effects of p38. Indeed, an early robust increase in TEA-sensitive potassium
      channel currents induced by DTDP is attenuated by p38 inhibition but not by
      caspase inhibition. Moreover, we found that activation of p38 is required for
      caspase 3 and 9 cleavage, suggesting that potassium currents enhancement is
      required for caspase activation. Finally, we observed that DTDP toxicity could be
      blocked with niacinamide or benzamide, inhibitors of poly (ADP-ribose)
      synthetase. Based on these findings, we conclude that oxidation of sulfhydryl
      groups on intracellular targets results in intracellular zinc release, p38
      phosphorylation, enhancement of potassium currents, caspase cleavage, energetic
      dysfunction, and translationally independent apoptotic cell death.

PMID- 11331361
TI  - Pyruvate released by astrocytes protects neurons from copper-catalyzed cysteine
      neurotoxicity.
AB  - We have found previously that astrocytes can provide cysteine to neurons.
      However, cysteine has been reported to be neurotoxic although it plays a pivotal
      role in regulating intracellular levels of glutathione, the major cellular
      antioxidant. Here, we show that cysteine toxicity is a result of hydroxyl
      radicals generated during cysteine autoxidation. Transition metal ions are
      candidates to catalyze this process. Copper substantially accelerates the
      autoxidation rate of cysteine even at submicromolar levels, whereas iron and
      other transition metal ions, including manganese, chromium, and zinc, are less
      efficient. The autoxidation rate of cysteine in rat CSF is equal to that observed
      in the presence of approximately 0.2 microm copper. In tissue culture tests, we
      found that cysteine toxicity depends highly on its autoxidation rate and on the
      total amount of cysteine being oxidized, suggesting that the toxicity can be
      attributed to the free radicals produced from cysteine autoxidation, but not to
      cysteine itself. We have also explored the in vivo mechanisms that protect
      against cysteine toxicity. Catalase and pyruvate were each found to inhibit the
      production of hydroxyl radicals generated by cysteine autoxidation. In tissue
      culture, they both protected primary neurons against cysteine toxicity catalyzed
      by copper. This protection is attributed to their ability to react with hydrogen
      peroxide, preventing the formation of hydroxyl radicals. Pyruvate, but not
      catalase or glutathione peroxidase, was detected in astrocyte-conditioned medium
      and CSF. Our data therefore suggest that astrocytes can prevent cysteine toxicity
      by releasing pyruvate.

PMID- 11331362
TI  - Semaphorin 3A-vascular endothelial growth factor-165 balance mediates migration
      and apoptosis of neural progenitor cells by the recruitment of shared receptor.
AB  - The dynamic and coordinated interaction between cells and their microenvironment
      controls cell migration, proliferation, and apoptosis, mediated by different cell
      surface molecules. We have studied the response of a neuroectodermal progenitor
      cell line, Dev, to a guidance molecule, semaphorin 3A (Sema3A), described
      previously as a repellent-collapsing signal for axons, and we have shown that
      Sema3A acts as a repellent guidance cue for migrating progenitor cells and, on
      prolonged application, induces apoptosis. Both repulsion and induction of cell
      death are mediated by neuropilin-1, the ligand-binding component of the Sema3A
      receptor. The vascular endothelial growth factor, VEGF165, antagonizes Sema3A
      induced apoptosis and promotes cell survival, migration, and proliferation.
      Surprisingly, repulsion by Sema3A also depends on expression of VEGFR1, a VEGF165
      receptor, expressed in Dev cells. Moreover, we found that these repulsive effects
      of Sema3A require tyrosine kinase activity, which can be attributed to VEGFR1.
      These results indicate that the balance between guidance molecules and angiogenic
      factors can modulate the migration, apoptosis (or survival), and proliferation of
      neural progenitor cells through shared receptors.

PMID- 11331363
TI  - High-fidelity transmission acquired via a developmental decrease in NMDA receptor
      expression at an auditory synapse.
AB  - Central auditory relay synapses in mature animals follow high-frequency inputs
      for computation of sound localization. In immature mice, however, transmission at
      the calyx of Held synapse in auditory brainstem was inaccurate for high-frequency
      inputs because the summed slow synaptic potential components caused aberrant
      firings or blocked action potentials. As the mice matured, synaptic potentials
      became shorter, with smaller and faster NMDA receptor components, thereby
      establishing the precise one-to-one transmission for high-frequency inputs.
      Developmental acquisition of this high-fidelity transmission could be mimicked
      experimentally in immature mice by blocking NMDA receptors with d(-)2-amino-5
      phosphonovaleric acid (d-APV). Furthermore, bilateral cochlear ablations at
      postnatal day 7 (P7) attenuated the developmental decrease of NMDA receptor
      expression and prevented the acquisition of high-fidelity transmission. We
      suggest that auditory activity, which begins at P10-P12 in mice, downregulates
      the expression of postsynaptic NMDA receptors, thereby contributing to the
      establishment of high-fidelity synaptic transmission.

PMID- 11331364
TI  - The neuronal microtubule-associated protein 1B is under homeoprotein
      transcriptional control.
AB  - To identify genes regulated by homeoprotein transcription factors in postnatal
      neurons, the DNA-binding domain (homeodomain) of Engrailed homeoprotein was
      internalized into rat cerebellum neurons. The internalized homeodomain (EnHD)
      acts as a competitive inhibitor of Engrailed and of several homeoproteins
      (Mainguy et al., 2000). Analysis by differential display revealed that
      microtubule-associated protein 1B (MAP1B) mRNA is upregulated by EnHD. This
      upregulation does not require protein synthesis, suggesting a direct effect of
      the homeodomain on MAP1B transcription. The promoter region of MAP1B was cut into
      several subdomains, and each subdomain was tested for its ability to bind
      Engrailed and EnHD and to associate with Engrailed-containing cerebellum nuclear
      extracts. In addition, the activity, and regulation by Engrailed, of each
      subdomain and of the entire promoter were evaluated in vivo by electroporation in
      the chick embryo neural tube. These experiments demonstrate that MAP1B promoter
      is regulated by Engrailed in vivo. Moreover, they show that one promoter domain
      that contains all ATTA homeoprotein cognate binding sites common to the rat and
      human genes is an essential element of this regulation. It is thus proposed that
      MAP1B, a cytoskeleton protein involved in neuronal growth and regeneration, is
      under homeoprotein transcriptional regulation.

PMID- 11331365
TI  - Ezrin-dependent promotion of glioma cell clonogenicity, motility, and invasion
      mediated by BCL-2 and transforming growth factor-beta2.
AB  - Ezrin belongs to the ezrin-radixin-moesin family proteins, which cross-link actin
      cytoskeleton and plasma membrane. Malignant glioma cells are paradigmatic for
      their strong migratory and invasive properties. Here, we report that the
      expression of dominant-negative ezrins inhibits clonogenicity, migration, and
      invasiveness of human malignant glioma cells. Furthermore, dominant-negative
      ezrins block hepatocyte growth factor (HGF)-mediated stimulation of clonogenicity
      and migration, without altering HGF-induced protein kinase B/Akt and focal
      adhesion kinase phosphorylation. Glioma cells expressing dominant-negative ezrins
      exhibit a shift of the BCL-2/BAX rheostat toward apoptosis, reduced
      alpha(V)beta(3) integrin expression and reduced matrix metalloproteinase (MMP)
      expression and activity. These changes are associated with a dramatic loss of
      transforming growth factor beta(2) (TGF-beta(2)) release. Exogenous
      supplementation of TGF-beta(2) overcomes the inhibitory effects of dominant
      negative ezrins on migration and clonogenicity. A neutralizing TGF-beta(2)
      antibody mimics the effects of dominant-negative ezrins on clonogenicity and
      migration. Exogenous HGF markedly induces TGF-beta(2) protein levels, and a
      neutralizing TGF-beta(2) antibody abolishes the HGF-mediated increase in glioma
      cell motility. Finally, TGF-beta(2) does not modulate BCL-2 or BAX expression,
      but BCL-2 gene transfer increases the levels of latent and active TGF-beta(2).
      Intracranial xenografts of U87MG glioma cells transfected with the dominant
      negative ezrins in athymic mice grow to significantly smaller volumes, and the
      median survival of these mice is 50 d compared with 28 d in the control group.
      These data define a novel pathway for HGF-induced glioma cell migration and
      invasion, which requires ezrin, changes in the BCL-2/BAX rheostat, and the
      induction of TGF-beta(2) expression in vitro, and underscore the important role
      of HGF signaling in vivo.

PMID- 11331366
TI  - Neuron-specific expression of mutant superoxide dismutase 1 in transgenic mice
      does not lead to motor impairment.
AB  - Mutations were identified in the Cu/Zn superoxide dismutase gene (SOD1) in
      approximately 15% of patients with familial amyotrophic lateral sclerosis.
      Transgenic animals expressing mutant SOD1 in all tissues develop an ALS-like
      phenotype. To determine whether neuron-specific expression of mutant SOD1 is
      sufficient to produce such a phenotype, we generated transgenic animals carrying
      the G37R mutation that is associated with the familial form of ALS (FALS), which
      is driven by the neurofilament light chain promoter. The transgenic animals
      express high levels of the human SOD1 protein in neuronal tissues, especially in
      the large motor neurons of the spinal cord, but they show no apparent motor
      deficit at up to 1.5 years of age. Our animal model suggests that neuron-specific
      expression of ALS-associated mutant human SOD1 may not be sufficient for the
      development of the disease in mice.

PMID- 11331367
TI  - Nerve growth factor rapidly induces prolonged acetylcholine release from cultured
      basal forebrain neurons: differentiation between neuromodulatory and neurotrophic
      influences.
AB  - Long-term exposure to nerve growth factor (NGF) is well established to have
      neurotrophic effects on basal forebrain cholinergic neurons, but its potential
      actions as a fast-acting neuromodulator are not as well understood. We report
      that NGF (0.1-100 ng/ml) rapidly (<60 min) and robustly enhanced constitutive
      acetylcholine (ACh) release (148-384% of control) from basal forebrain cultures
      without immediate persistent increases in choline acetyltransferase activity.
      More ACh was released in response to NGF when exposure was coupled with a higher
      depolarization level, suggesting activity dependence. In a long-term potentiation
      like manner, brief NGF exposure (10 ng/ml; 60 min) induced robust and prolonged
      increases in ACh release, a capacity that was shared with the other
      neurotrophins. K252a (10-100 nm), BAPTA-AM (25 microm), and Cd(2+) (200 microm)
      prevented NGF enhancement of ACh release, suggesting the involvement of TrkA
      receptors, Ca(2+), and voltage-gated Ca(2+) channels, respectively. Forskolin (10
      microm), a cAMP generator, enhanced constitutive ACh release but did not interact
      synergistically with NGF. Tetrodotoxin (1 microm) and cycloheximide (2 microm)
      did not prevent NGF-induced ACh release, indicative of action at the level of the
      cholinergic nerve terminal and that new protein synthesis is not required for
      this neurotransmitter-like effect, respectively. In contrast, after a 24 hr NGF
      treatment, distinct protein synthesis-dependent and independent effects on
      choline acetyltransferase activity and ACh release were observed. These results
      indicate that neuromodulator/neurotransmitter-like (protein synthesis
      independent) and neurotrophic (translation-dependent) actions likely make
      distinct contributions to the enhancement of cholinergic activity by NGF.

PMID- 11331368
TI  - Increased histone acetyltransferase and lysine acetyltransferase activity and
      biphasic activation of the ERK/RSK cascade in insular cortex during novel taste
      learning.
AB  - Changes in gene expression are thought to be involved in neuronal plasticity
      associated with learning and memory. Although acetylation of lysine residues on
      histones by histone acetyltransferases (HAT) is an obligatory component of
      transcription, HAT activity has been largely ignored in studies of the nervous
      system. We developed a new model for studying novel taste learning using novel
      solid food presentation to nondeprived animals. Using this behavioral paradigm,
      we investigated short- and long-term regulation of lysine acetyltransferase
      activity and the ERK/mitogen-activated protein kinase (MAPK)/RSK cascade in
      insular cortex, a CNS region known to be crucial for the formation of novel taste
      memories. We observed that novel taste learning elicited biphasic (acute and long
      lasting) activation of two distinct lysine acetyltransferase activities along
      with the ERK/MAPK cascade in insular cortex. In vitro studies revealed that the
      ERK cascade could regulate the lysine acetylation of a 42 kDa lysine
      acetyltransferase substrate, suggesting a causal relationship between ERK
      activation and lysine acetyltransferase activity in insular cortex. Overall, our
      studies reveal an unanticipated long-lasting activation of insular cortex signal
      transduction cascades in novel taste learning. Furthermore, our studies suggest
      the hypothesis that acute and long-term ERK activation and lysine-histone
      acetyltransferase activation may play a role in regulating gene expression in
      single-trial learning and long-term memory formation.

PMID- 11331369
TI  - Proliferation of NG2-positive cells and altered oligodendrocyte numbers in the
      contused rat spinal cord.
AB  - Given the numerous reparative roles glia may play after spinal cord injury (SCI),
      glial proliferation and cell number were examined in a model of traumatic SCI.
      Emphasis was placed on analysis of oligodendrocytes and NG2-positive (NG2+)
      cells, an endogenous cell population that may be involved in oligodendrocyte
      replacement. Overall, proliferation (assessed by bromodeoxyuridine incorporation)
      was markedly elevated during the first 2 weeks after injury and declined
      thereafter; a large portion of these dividing cells likely consisted of microglia
      macrophages. Although the total number of NG2+ cells in the epicenter was reduced
      by half, we noted protracted proliferation in surviving NG2+ cells, with values
      sevenfold greater than in uninjured controls. Elevated proliferation of NG2+
      cells persisted throughout the first 4 weeks after injury. However, the absolute
      number of NG2+ cells was not increased over controls, suggesting that the
      daughter cells either did not survive or they differentiated into other cell
      types. As expected, oligodendrocyte numbers were drastically altered after SCI.
      By 7 d after injury, the number of oligodendrocytes at the impact site was
      reduced by 93%. Despite ongoing tissue loss, the number of oligodendrocytes in
      spared tissue rose threefold at 14 d after injury. Although the function of NG2+
      cells within the spinal cord is not completely understood, several studies
      suggest that they may differentiate into oligodendrocytes. Thus, proliferating
      NG2+ cells may contribute to the increased oligodendrocyte number observed at 2
      weeks after injury. Future studies are required, however, to definitively
      determine the role NG2+ cells play in oligodendrocyte genesis, remyelination, and
      other post-injury events.

PMID- 11331370
TI  - Macrophages are eliminated from the injured peripheral nerve via local apoptosis
      and circulation to regional lymph nodes and the spleen.
AB  - The present study investigated the fate of macrophages in peripheral nerves
      undergoing Wallerian degeneration, especially their disappearance from the
      injured nerves after phagocytosis of axonal and myelin debris. Wallerian
      degeneration was induced in adult male C57Bl/6 mice by transecting the right
      sciatic nerve. Five days after transection, the male sciatic nerves were
      transplanted into female recipient mice by placing them exactly parallel to the
      host sciatic nerves. Nerves of the female recipient mice were also transected to
      induce breakdown of the blood-nerve barrier in the host animal. Apoptosis was
      assessed by morphological, immunohistochemical (activated caspase-3), and
      molecular (DNA fragmentation) methods in transplanted, recipient, and in control
      nerves. A subpopulation of macrophages within the degenerating nerves died
      locally by apoptosis in each experiment. The fate of the male macrophages within
      the transplanted nerves and the host organism was investigated by in situ
      hybridization with a Y-chromosome-specific DNA probe (145SC5). In situ
      hybridization specifically stained cells within the transplanted male nerve. Y
      chromosome-positive cells were detected not only inside the transplanted nerve,
      but also inside the female host nerve, the perineurial tissue, the local
      perineurial blood vessels, draining lymph nodes and the spleen of the female
      host, suggesting hematogenous as well as lymphatic elimination of macrophages
      from the injured nerve. These data indicate that local apoptosis and systemic
      elimination via circulation to the local lymph nodes and the spleen are involved
      in the disappearance of macrophages from the injured peripheral nervous system.

PMID- 11331371
TI  - Loss of the major GABA(A) receptor subtype in the brain is not lethal in mice.
AB  - The alpha1beta2gamma2 is the most abundant subtype of the GABA(A) receptor and is
      localized in many regions of the brain. To gain more insight into the role of
      this receptor subtype in the modulation of inhibitory neurotransmission, we
      generated mice lacking either the alpha1 or beta2 subunit. In agreement with the
      reported abundance of this subtype, >50% of total GABA(A) receptors are lost in
      both alpha1-/- and beta2-/- mice. Surprisingly, homozygotes of both mouse lines
      are viable, fertile, and show no spontaneous seizures. Initially half of the
      alpha1-/- mice died prenatally or perinatally, but they exhibited a lower
      mortality rate in subsequent generations, suggesting some phenotypic drift and
      adaptive changes. Both adult alpha1-/- and beta2-/- mice demonstrate normal
      performances on the rotarod, but beta2-/- mice displayed increased locomotor
      activity. Purkinje cells of the cerebellum primarily express alpha1beta2gamma2
      receptors, and in electrophysiological recordings from alpha1-/- mice GABA
      currents in these neurons are dramatically reduced, and residual currents have a
      benzodiazepine pharmacology characteristic of alpha2- or alpha3-containing
      receptors. In contrast, the cerebellar Purkinje neurons from beta2-/- mice have
      only a relatively small reduction of GABA currents. In beta2-/- mice expression
      levels of all six alpha subunits are reduced by approximately 50%, suggesting
      that the beta2 subunit can coassemble with alpha subunits other than just alpha1.
      Our data confirm that alpha1beta2gamma2 is the major GABA(A) receptor subtype in
      the murine brain and demonstrate that, surprisingly, the loss of this receptor
      subtype is not lethal.

PMID- 11331372
TI  - Suppression of neuronal hyperexcitability and associated delayed neuronal death
      by adenoviral expression of GABA(C) receptors.
AB  - The excessive neuronal excitation underlying several clinically important
      diseases is often treated with GABA allosteric modulators in an attempt to
      enhance inhibition. An alternative strategy would be to enhance directly the
      sensitivity of postsynaptic neurons to GABA. The GABA(C) receptor, normally found
      only in the retina, is more sensitive to GABA and demonstrates little
      desensitization compared with the GABA(A) receptor. We constructed an adenovirus
      vector that expressed cDNA for both the GABA(C) receptor rho(1) subunit and a
      green fluorescent protein (GFP) reporter and used it to transduce cultured
      hippocampal neurons. Transduced neurons were identified by fluorescence, double
      immunocytochemistry proved colocalization of the rho(1) protein and the reporter,
      Western blot verified the expected molecular masses, and electrophysiological and
      pharmacological properties confirmed the presence of functional GABA(C)
      receptors. rho(1)-GFP transduction resulted in an increased density of GABA(A)
      receptors as well as expression of novel GABA(C) receptors. This effect was not
      reproduced by addition of TTX or Mg(2+) to the culture medium to reduce action
      potentials or synaptic activity. In a model of neuronal hyperexcitability induced
      by chronic blockade of glutamate receptors, expression of GABA(C) receptors
      abolished the hyperactivity and the consequent delayed neuronal death. Adenovirus
      mediated neuronal GABA(C) receptor engineering, via its dual mechanism of
      inhibition, may offer a way of inhibiting only those hyperexcitable neurons
      responsible for clinical problems, avoiding the generalized nervous system
      depression associated with pharmacological therapy.

PMID- 11331373
TI  - Pituitary control of BK potassium channel function and intrinsic firing
      properties of adrenal chromaffin cells.
AB  - The discovery that the hypothalamic-pituitary-adrenocortical (HPA) endocrine
      stress axis controls an alternative splicing decision in chromaffin Slo-encoded
      BK (big potassium) channels raised the possibility that activation of the HPA
      could serve as a mechanism to tune the intrinsic electrical properties of
      epinephrine-secreting adrenal chromaffin cells. To test this, we compared BK
      functional properties and cell excitability in chromaffin cells from normal and
      hypophysectomized (pituitary-ablated) rats. Hypophysectomy was found to alter the
      voltage dependence and kinetics of BK gating, making channels less accessible for
      activation from rest. Perforated-patch recordings revealed changes in action
      potential waveform and repetitive firing properties. The maximum number of spikes
      that could be elicited with a 2 sec depolarizing current pulse was reduced by
      approximately 50% by hypophysectomy. The results indicate that pituitary hormones
      can adapt the mechanics of adrenal catecholamine release by tailoring BK channel
      function.

PMID- 11331374
TI  - Differential expression of the small-conductance, calcium-activated potassium
      channel SK3 is critical for pacemaker control in dopaminergic midbrain neurons.
AB  - The physiological activity of dopaminergic midbrain (DA) neurons is important for
      movement, cognition, and reward. Altered activity of DA neurons is a key finding
      in schizophrenia, but the cellular mechanisms have not been identified. Recently,
      KCNN3, a gene that encodes a member (SK3) of the small-conductance, calcium
      activated potassium (SK) channels, has been proposed as a candidate gene for
      schizophrenia. However, the functional role of SK3 channels in DA neurons is
      unclear. We combined patch-clamp recordings with single-cell RT-PCR and confocal
      immunohistochemistry in mouse midbrain slices to study the function of
      molecularly defined SK channels in DA neurons. Biophysical and pharmacological
      analysis, single-cell mRNA, and protein expression profiling strongly suggest
      that SK3 channels mediate the calcium-dependent afterhyperpolarization in DA
      neurons. Perforated patch recordings of DA neurons in the substantia nigra (SN)
      demonstrated that SK3 channels dynamically control the frequency of spontaneous
      firing. In addition, SK3 channel activity was essential to maintain the high
      precision of the intrinsic pacemaker of DA SN neurons. In contrast, in the
      ventral tegmental area, DA neurons displayed significantly smaller SK currents
      and lower SK3 protein expression. In these DA neurons, SK3 channels were not
      involved in pacemaker control. Accordingly, they discharged in a more irregular
      manner compared with DA SN neurons. Thus, our study shows that differential SK3
      channel expression is a critical molecular mechanism in DA neurons to control
      neuronal activity. This provides a cellular framework to understand the
      functional consequences of altered SK3 expression, a candidate disease mechanism
      for schizophrenia.

PMID- 11331375
TI  - Neurotrophic factors and receptors in the immature and adult spinal cord after
      mechanical injury or kainic acid.
AB  - Delivery of neurotrophic factors to the injured spinal cord has been shown to
      stimulate neuronal survival and regeneration. This indicates that a lack of
      sufficient trophic support is one factor contributing to the absence of
      spontaneous regeneration in the mammalian spinal cord. Regulation of the
      expression of neurotrophic factors and receptors after spinal cord injury has not
      been studied in detail. We investigated levels of mRNA-encoding neurotrophins,
      glial cell line-derived neurotrophic factor (GDNF) family members and related
      receptors, ciliary neurotrophic factor (CNTF), and c-fos in normal and injured
      spinal cord. Injuries in adult rats included weight-drop, transection, and
      excitotoxic kainic acid delivery; in newborn rats, partial transection was
      performed. The regulation of expression patterns in the adult spinal cord was
      compared with that in the PNS and the neonate spinal cord. After mechanical
      injury of the adult rat spinal cord, upregulations of NGF and GDNF mRNA occurred
      in meningeal cells adjacent to the lesion. BDNF and p75 mRNA increased in
      neurons, GDNF mRNA increased in astrocytes close to the lesion, and GFRalpha-1
      and truncated TrkB mRNA increased in astrocytes of degenerating white matter. The
      relatively limited upregulation of neurotrophic factors in the spinal cord
      contrasted with the response of affected nerve roots, in which marked increases
      of NGF and GDNF mRNA levels were observed in Schwann cells. The difference
      between the ability of the PNS and CNS to provide trophic support correlates with
      their different abilities to regenerate. Kainic acid delivery led to only weak
      upregulations of BDNF and CNTF mRNA. Compared with several brain regions, the
      overall response of the spinal cord tissue to kainic acid was weak. The relative
      sparseness of upregulations of endogenous neurotrophic factors after injury
      strengthens the hypothesis that lack of regeneration in the spinal cord is
      attributable at least partly to lack of trophic support.

PMID- 11331376
TI  - Rapid anatomical plasticity of horizontal connections in the developing visual
      cortex.
AB  - Experience can dramatically alter the responses of cortical neurons. During a
      critical period in the development of visual cortex, these changes are extremely
      rapid, taking place in 2 d or less. Anatomical substrates of these changes have
      long been sought, primarily in alterations in the principal visual input from the
      thalamus, but the significant changes that have been found take 1 week. Recent
      results indicate that the initial physiological changes in the cortical circuit
      take place outside of the primary input layer. We now find that rapid plasticity
      of binocular responses in the upper layers of cortex is mirrored by similarly
      rapid anatomical changes in the horizontal connections between ocular dominance
      columns in the upper layers, which reorganize within 2 d.

PMID- 11331377
TI  - Immature neurons from CNS stem cells proliferate in response to platelet-derived
      growth factor.
AB  - Identifying external signals involved in the regulation of neural stem cell
      proliferation and differentiation is fundamental to the understanding of CNS
      development. In this study we show that platelet-derived growth factor (PDGF) can
      act as a mitogen for neural precursor cells. Multipotent stem cells from
      developing CNS can be maintained in a proliferative state under serum-free
      conditions in the presence of fibroblast growth factor-2 (FGF2) and induced to
      differentiate into neurons, astrocytes, and oligodendrocytes on withdrawal of the
      mitogen. PDGF has been suggested to play a role during the differentiation into
      neurons. We have investigated the effect of PDGF on cultured stem cells from
      embryonic rat cortex. The PDGF alpha-receptor is constantly expressed during
      differentiation of neural stem cells but is phosphorylated only after PDGF-AA
      treatment. In contrast, the PDGF beta-receptor is hardly detectable in
      uncommitted cells, but its expression increases during differentiation. We show
      that PDGF stimulation leads to c-fos induction, 5'-bromo-2'deoxyuridine
      incorporation, and an increase in the number of immature cells stained with
      antibodies to neuronal markers. Our findings suggest that PDGF acts as a mitogen
      in the early phase of stem cell differentiation to expand the pool of immature
      neurons.

PMID- 11331379
TI  - Complex trait analysis of the hippocampus: mapping and biometric analysis of two
      novel gene loci with specific effects on hippocampal structure in mice.
AB  - Notable differences in hippocampal structure are associated with intriguing
      differences in development and behavioral capabilities. We explored genetic and
      environmental factors that modulate hippocampal size, structure, and cell number
      using sets of C57BL/6J (B6) and DBA/2J (D2) mice; their F1 and F2 intercrosses (n
      = 180); and 35 lines of BXD recombinant inbred (RI) strains. Hippocampal weights
      of the parental strains differ by 20%. Estimates of granule cell number also
      differ by approximately 20%. Hippocampal weights of RI strains range from 21 to
      31 mg, and those of individual F2 mice range from 23 to 36 mg (bilateral
      weights). Volume and granule cell number are well correlated (r = 0.7-0.8).
      Significant variation is associated with differences in age and sex. The
      hippocampus increases in weight by 0.24 mg per month, and those of males are 0.55
      mg heavier (bilateral) than those of females. Heritability of variation is
      approximately 50%, and half of this genetic variation is generated by two
      quantitative trait loci that map to chromosome 1 (Hipp1a: genome-wide p < 0.005,
      between 65 and 100 cM) and to chromosome 5 (Hipp5a, p < 0.05, between 15 and 40
      cM). These are among the first gene loci known to produce normal variation in
      forebrain structure. Hipp1a and Hipp5a individually modulate hippocampal weight
      by 1.0-2.0 mg, an effect size greater than that generated by age or sex. The Hipp
      gene loci modulate neuron number in the dentate gyrus, collectively shifting the
      population up or down by as much as 200,000 cells. Candidate genes for the Hipp
      loci include Rxrg and Fgfr3.

PMID- 11331378
TI  - Endogenous brain-derived neurotrophic factor and neurotrophin-3 antagonistically
      regulate survival of axotomized corticospinal neurons in vivo.
AB  - Neuronal growth factors regulate the survival of neurons by their survival and
      death-promoting activity on distinct populations of neurons. The neurotrophins
      nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and
      neurotrophin-3 (NT-3) promote neuronal survival via tyrosine kinase (Trk)
      receptors, whereas NGF and BDNF can also induce apoptosis in developing neurons
      through p75(NTR) receptors in the absence of their respective Trk receptors.
      Using mutant mice and inactivation of neurotrophins and their receptors with
      antibodies in rats, we show that endogenous NT-3 induces death of adult BDNF
      dependent, axotomized corticospinal neurons (CSNs). When NT-3 is neutralized, the
      neurons survive even without BDNF, suggesting complete antagonism. Whereas
      virtually all unlesioned and axotomized CSNs express both trkB and trkC mRNA, p75
      is barely detectable in unlesioned CSNs but strongly upregulated in axotomized
      CSNs by day 3 after lesion, the time point when cell death occurs. Blocking
      either cortical TrkC or p75(NTR) receptors alone prevents death, indicating that
      the opposing actions of NT-3 and BDNF require their respective Trk receptors, but
      induction of death depends on p75(NTR) cosignaling. The results show that
      neuronal survival can be regulated antagonistically by neurotrophins and that
      neurotrophins can induce neuronal death in the adult mammalian CNS. We further
      present evidence that signaling of tyrosine kinase receptors of the trk family
      can be crucially involved in the promotion of neuronal death in vivo.

PMID- 11331380
TI  - Retrograde carbon monoxide is required for induction of long-term potentiation in
      rat superior cervical ganglion.
AB  - Carbon monoxide (CO), produced in the body by the enzyme heme oxygenase (HO), has
      been suggested as a retrograde synaptic messenger with a prominent role in the
      long-term potentiation (LTP) of certain areas of the brain. LTP of sympathetic
      ganglia is 5-HT(3) receptor-dependent and has been shown to require nitric oxide
      for the maintenance, but not for the induction, phase. We investigated the
      possibility of CO being required for the induction of ganglionic LTP.
      Pretreatment of rat isolated superior cervical ganglia with oxyhemoglobin (25-100
      microm) completely blocked LTP. In the same ganglia, prolonged washout of
      oxyhemoglobin did not uncover any potentiation of the compound action potential.
      Oxyhemoglobin had no significant effect on the maintenance phase in ganglia with
      established LTP. Pretreatment of ganglia with the HO inhibitor zinc
      protoporphyrin-IX (ZnPP) (10 microm) completely and irreversibly prevented the
      expression of tetanus-evoked LTP. However, in the same ganglia, after superfusion
      of CO in the presence of ZnPP, tetanic stimulation readily evoked LTP. No effect
      was seen on the maintenance phase when ZnPP was superfused on ganglia with
      established LTP. Pretreatment of ganglia with the 5-HT(3) receptor antagonist
      ondansetron (0.4 microm) alone completely and irreversibly blocked LTP. However,
      in the presence of CO, ondansetron did not block LTP. These results suggest that
      activation of 5-HT(3) receptors may be involved in the production of CO. The
      results also suggest that CO, probably originating outside the presynaptic nerve
      terminal, is involved in the induction of LTP.

PMID- 11331381
TI  - Enhancement of sensorimotor behavioral recovery in hemiparkinsonian rats with
      intrastriatal, intranigral, and intrasubthalamic nucleus dopaminergic
      transplants.
AB  - One of the critical variables that influences the efficacy of clinical neural
      transplantation for Parkinson's disease (PD) is optimal graft placement. The
      current transplantation paradigm that focuses on ectopic placement of fetal
      grafts in the striatum (ST) fails to reconstruct the basal ganglia circuitry or
      normalize neuronal activity in important basal ganglia structures, such as the
      substantia nigra (SN) and the subthalamic nucleus (STN). The aim of this study
      was to investigate a multitarget neural transplantation strategy for PD by
      assessing whether simultaneous dopaminergic transplants in the ST, SN, and STN
      induce functional recovery in hemiparkinsonian rats. Forty-six female Wistar rats
      with unilateral 6-hydroxydopamine lesions of the nigrostriatal pathway were
      randomly divided into eight groups and received lesions only or injections of
      900,000 embryonic rat ventral mesencephalic cells in the (1) ST, (2) SN, (3) STN,
      (4) ST and SN, (5) ST, SN, and STN, (6) ST and STN, or (7) SN and STN. The number
      of cells transplanted was equally divided among grafting sites. Animals with two
      grafts received 450,000 cells in each structure, and animals with three grafts
      received 300,000 cells per structure. Recovery was assessed by amphetamine
      induced rotations and the stepping tests. Graft survival was assessed using
      tyrosine hydroxylase immunohistochemistry. At 8 weeks after transplantation,
      simultaneous dopaminergic transplants in the ST, SN, and STN induced significant
      improvement in rotational behavior and stepping test scores. Intrastriatal
      transplants were associated with significant recovery of rotational asymmetry,
      whereas SN and STN transplants were associated with improved forelimb function
      scores. These results suggest that restoration of dopaminergic activity to
      multiple basal ganglia targets, such as the ST and SN, or the ST and STN,
      promotes a more complete functional recovery of complex sensorimotor behaviors. A
      multitarget transplant strategy aimed at optimizing dopaminergic reinnervation of
      the basal ganglia may be crucial in improving clinical outcomes in PD patients.

PMID- 11331382
TI  - Adaptive locomotor plasticity in chronic spinal cats after ankle extensors
      neurectomy.
AB  - After lateral gastrocnemius-soleus (LGS) nerve section in intact cats, a rapid
      locomotor compensation involving synergistic muscles occurs and is accompanied by
      spinal reflex changes. Only some of these changes are maintained after acute
      spinalization, indicating the involvement of descending pathways in functional
      recovery. Here, we address whether the development of these adaptive changes is
      dependent on descending pathways. The left LGS nerve was cut in three chronic
      spinal cats. Combined kinematics and electromyographic (EMG) recordings were
      obtained before and for 8 d after the neurectomy. An increased yield at the ankle
      was present early after neurectomy and, as in nonspinal cats, was gradually
      reduced within 8 d. Compensation involved transient changes in step cycle
      structure and a longer term increase in postcontact medial gastrocnemius (MG) EMG
      activity. Precontact MG EMG only increased in one of three cats. In a terminal
      experiment, the influence of group I afferents from MG and LGS on stance duration
      was measured in two cats. LGS effectiveness at increasing stance duration was
      largely decreased in both cats. MG effectiveness was only slightly changed:
      increased in one cat and decreased in another. In cat 3, the plantaris nerve was
      cut after LGS recovery. The recovery time courses from both neurectomies were
      similar (p > 0.8), suggesting that this spinal compensation is likely a
      generalizable adaptive strategy. From a functional perspective, the spinal cord
      therefore must be considered capable of adaptive locomotor plasticity after motor
      nerve lesions. This finding is of prime importance to the understanding of
      functional plasticity after spinal injury.

PMID- 11331383
TI  - Analysis of the activity-deprived zebrafish mutant macho reveals an essential
      requirement of neuronal activity for the development of a fine-grained visuotopic
      map.
AB  - The formation of a retinotopic map is thought to involve an activity-independent
      molecular phase for early steps of both axon pathfinding and projection and a
      later phase in which cross talk between retinal ganglion cells (RGCs) and tectal
      neurons modifies and refines the neuronal connections. We report that the
      maturation of the retinotopic map in the zebrafish tectum involves activity
      dependent processes. Zebrafish larvae mutant for the gene macho (mao) lack
      neuronal activity in RGCs and also display an enlarged retinotectal projection
      field but no significant increase in single axon length. This morphological
      defect can be phenocopied by raising larvae under TTX-induced neural impulse
      blockade. The effect of activity deprivation is dependent on the developmental
      stage. The projection phenotype in mao as well as in the TTX-treated larvae
      develops between 4 and 6 d post-fertilization (dpf), after complete tectal
      coverage is first achieved. Electrophysiological recordings of RGCs in wild-type
      and mao zebrafish larvae reveal a temporally regulated reduction of sodium
      current in the mutant between 5 and 6 dpf. This coincides with the time of the
      axonal projection shifting on the tectum to compensate for the disparate growth
      patterns of the retina and the tectum. Our genetic and physiological analyses
      suggest a model in which neuronal activity in RGCs is needed for the
      establishment of morphological plasticity.

PMID- 11331384
TI  - Tactile responses in the granule cell layer of cerebellar folium crus IIa of
      freely behaving rats.
AB  - We recorded activity from the granule cell layer (GCL) of cerebellar folium Crus
      IIa as freely moving rats engaged in a variety of natural behaviors, including
      grooming, eating, and free tactile exploration. Multiunit responses in the 1000
      4500 Hz range were found to be strongly correlated with tactile stimulation of
      lip and whisker (perioral) regions. These responses occurred regardless of
      whether the stimulus was externally or self-generated and during both active and
      passive touch. In contrast, perioral movements that did not tactually stimulate
      this region of the face (e.g., chewing) produced no detectable increases in GCL
      activity. In addition, GCL responses were not correlated with movement extremes.
      When rats used their lips actively for palpation and exploration, the tactile
      responses in the GCL were not detectably modulated by ongoing jaw movements.
      However, active palpation and exploratory behaviors did result in the largest and
      most continuous bursts of GCL activity: responses were on average 10% larger and
      50% longer during palpation and exploration than during grooming or passive
      stimulation. Although activity levels differed between behaviors, the position
      and spatial extent of the peripheral receptive field was similar over all
      behaviors that resulted in tactile input. Overall, our data suggest that the 1000
      4500 Hz multiunit responses in the Crus IIa GCL of awake rats are correlated with
      tactile input rather than with movement or any movement parameter and that these
      responses are likely to be of particular importance during the acquisition of
      sensory information by perioral structures.

PMID- 11331385
TI  - Spatiotemporal maps of brain activity underlying word generation and their
      modification during repetition priming.
AB  - Spatiotemporal maps of brain activity based on magnetoencephalography were used
      to observe sequential stages in language processing and their modification during
      repetition priming. Subjects performed word-stem completion and produced either
      novel or repeated (primed) words across trials. Activation passes from primary
      visual cortex (activated at approximately 100 msec after word presentation), to
      left anteroventral occipital ( approximately 180 msec), to cortex in and near
      Wernicke's ( approximately 210 msec) and then Broca's ( approximately 370 msec)
      areas. In addition, a posteroventral temporal area is activated simultaneously
      with posterosuperior temporal cortex. This area shows an early ( approximately
      200-245 msec) increase in activation to repeated word stems. In contrast,
      prefrontal and anterior temporal regions showed activity reductions to repeated
      word stems late ( approximately 365-500 msec) in processing. These results tend
      to support classical models of language and suggest that an effect of direct item
      repetition is to allow word-form processing to increase its contribution to task
      performance while concurrently allowing reductions in time-consuming frontal
      temporal processing.

PMID- 11331386
TI  - 5-HT2A receptors stimulate ACTH, corticosterone, oxytocin, renin, and prolactin
      release and activate hypothalamic CRF and oxytocin-expressing cells.
AB  - The 5-HT(2A/2C) agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl
      (DOI) stimulates hypothalamic neurons to increase the secretion of several
      hormones. This study addressed two questions: 1) are the neuroendocrine effects
      of DOI mediated via activation of 5-HT(2A) receptors; and 2) which neurons are
      activated by 5-HT(2A) receptors. The 5-HT(2A) antagonist (+)-alpha-(2,3
      dimethoxyphenyl)-1-[2-(4-fluorophenylethyl)]-4-piperidinemethanol (MDL 100,907;
      0.001, 0.01, or 0.1 mg/kg, s.c.) was administered before rats were challenged
      with DOI (2.5 mg/kg, i.p.). MDL 100,907 produced a dose-dependent inhibition
      (ED(50) congruent with 0.001 mg/kg) of the effect of DOI on plasma levels of
      ACTH, corticosterone, oxytocin, prolactin, and renin without altering basal
      hormone levels. Complete blockade of the effect of DOI was achieved for all
      hormones at MDL 100,907 doses of 0.01-0.1 mg/kg. In a parallel experiment, DOI
      was injected 2 hr before killing to determine its effects on the expression of
      Fos, the product of the immediate early gene c-fos. DOI induced an increase in
      Fos immunoreactivity in corticotropin-releasing factor (CRF) and in oxytocin
      expressing neurons but not in vasopressin-containing neurons in the hypothalamic
      paraventricular nucleus or CRF cells in the amygdala. Pretreatment with MDL
      100,907 (0.1 mg/kg, s.c.) blocked the DOI-induced increase in Fos expression in
      all regions including the hypothalamus, amygdala (central and corticomedial), bed
      nucleus of the stria terminalis, and prefrontal cortical regions. The combined
      neuroanatomical and pharmacological observations suggest that the neuroendocrine
      responses to DOI are mediated by activation of neurons in the hypothalamic
      paraventricular nucleus and associated circuitry. Furthermore, selective
      activation of 5-HT(2A) receptors mediates the hormonal and Fos-inducing effects
      of DOI.

PMID- 11331387
TI  - Layer-specific intracolumnar and transcolumnar functional connectivity of layer V
      pyramidal cells in rat barrel cortex.
AB  - Layer V pyramidal cells in rat barrel cortex are considered to play an important
      role in intracolumnar and transcolumnar signal processing. However, the precise
      circuitry mediating this processing is still incompletely understood. Here we
      obtained detailed maps of excitatory and inhibitory synaptic inputs onto the two
      major layer V pyramidal cell subtypes, intrinsically burst spiking (IB) and
      regular spiking (RS) cells, using a combination of caged glutamate photolysis,
      whole-cell patch-clamp recording, and three-dimensional reconstruction of
      biocytin-labeled cells. To excite presynaptic neurons with laminar specificity,
      the release of caged glutamate was calibrated and restricted to small areas of 50
      x 50 microm in all cortical layers and in at least two neighboring barrel-related
      columns. IB cells received intracolumnar excitatory input from all layers, with
      the largest EPSP amplitudes originating from neurons in layers IV and VI.
      Prominent transcolumnar excitatory inputs were provided by presynaptic neurons
      also located in layers IV, V, and VI of neighboring columns. Inhibitory inputs
      were rare. In contrast, RS cells received distinct intracolumnar inhibitory
      inputs, especially from layers II/III and V. Intracolumnar excitatory inputs to
      RS cells were prominent from layers II-V, but relatively weak from layer VI.
      Conspicuous transcolumnar excitatory inputs could be evoked solely in layers IV
      and V. Our results show that layer V pyramidal cells are synaptically driven by
      presynaptic neurons located in every layer of the barrel cortex. RS cells seem to
      be preferentially involved in intracolumnar signal processing, whereas IB cells
      effectively integrate excitatory inputs across several columns.

PMID- 11331388
TI  - Status epilepticus causes necrotic damage in the mediodorsal nucleus of the
      thalamus in immature rats.
AB  - Status epilepticus (StE) in immature rats causes long-term functional impairment.
      Whether this is associated with structural alterations remains controversial. The
      present study was designed to test the hypothesis that StE at an early age
      results in neuronal loss. StE was induced with lithium-pilocarpine in 12-d-old
      rats, and the presence of neuronal damage was investigated in the brain from 12
      hr up to 1 week later using silver and Fluoro-Jade B staining techniques.
      Analysis of the sections indicated consistent neuronal damage in the central and
      lateral segments of the mediodorsal nucleus of the thalamus, which was confirmed
      using adjacent cresyl violet-stained preparations. The mechanism of thalamic
      damage (necrosis vs apoptosis) was investigated further using TUNEL,
      immunohistochemistry for caspase-3 and cytochrome c, and electron microscopy.
      Activated microglia were detected using OX-42 immunohistochemistry. The presence
      of silver and Fluoro-Jade B-positive degenerating neurons in the mediodorsal
      thalamic nucleus was associated with the appearance of OX-42-immunopositive
      activated microglia but not with the expression of markers of programmed cell
      death, caspase-3, or cytochrome c. Electron microscopy revealed necrosis of the
      ultrastructure of damaged neurons, providing further evidence that the mechanism
      of StE-induced damage in the mediodorsal thalamic nucleus at postnatal day 12 is
      necrosis rather than apoptosis. Finally, these data together with previously
      described functions of the medial and lateral segments of the mediodorsal
      thalamic nucleus suggest that some functions, such as adaptation to novelty,
      might become compromised after StE early in development.

PMID- 11331389
TI  - Layer-specific input to distinct cell types in layer 6 of monkey primary visual
      cortex.
AB  - Layer 6 of monkey V1 contains a physiologically and anatomically diverse
      population of excitatory pyramidal neurons. Distinctive arborization patterns of
      axons and dendrites within the functionally specialized cortical layers define
      eight types of layer 6 pyramidal neurons and suggest unique information
      processing roles for each cell type. To address how input sources contribute to
      cellular function, we examined the laminar sources of functional excitatory input
      onto individual layer 6 pyramidal neurons using scanning laser photostimulation.
      We find that excitatory input sources correlate with cell type. Class I neurons
      with axonal arbors selectively targeting magnocellular (M) recipient layer
      4Calpha receive input from M-dominated layer 4B, whereas class I neurons whose
      axonal arbors target parvocellular (P) recipient layer 4Cbeta receive input from
      P-dominated layer 2/3. Surprisingly, these neuronal types do not differ
      significantly in the inputs they receive directly from layers 4Calpha or 4Cbeta.
      Class II cells, which lack dense axonal arbors within layer 4C, receive
      excitatory input from layers targeted by their local axons. Specifically, type
      IIA cells project axons to and receive input from the deep but not superficial
      layers. Type IIB neurons project to and receive input from the deepest and most
      superficial, but not middle layers. Type IIC neurons arborize throughout the
      cortical layers and tend to receive inputs from all cortical layers. These
      observations have implications for the functional roles of different layer 6 cell
      types in visual information processing.

PMID- 11331390
TI  - Reorganization of motor and somatosensory cortex in upper extremity amputees with
      phantom limb pain.
AB  - Phantom limb pain (PLP) in amputees is associated with reorganizational changes
      in the somatosensory system. To investigate the relationship between
      somatosensory and motor reorganization and phantom limb pain, we used focal
      transcranial magnetic stimulation (TMS) of the motor cortex and neuroelectric
      source imaging of the somatosensory cortex (SI) in patients with and without
      phantom limb pain. For transcranial magnetic stimulation, recordings were made
      bilaterally from the biceps brachii, zygomaticus, and depressor labii inferioris
      muscles. Neuroelectric source imaging of the EEG was obtained after somatosensory
      stimulation of the skin overlying face and hand. Patients with phantom limb pain
      had larger motor-evoked potentials from the biceps brachii, and the map of
      outputs was larger for muscles on the amputated side compared with the intact
      side. The optimal scalp positions for stimulation of the zygomaticus and
      depressor labii inferioris muscles were displaced significantly more medially
      (toward the missing hand representation) in patients with phantom limb pain only.
      Neuroelectric source imaging revealed a similar medial displacement of the dipole
      center for face stimulation in patients with phantom limb pain. There was a high
      correlation between the magnitude of the shift of the cortical representation of
      the mouth into the hand area in motor and somatosensory cortex and phantom limb
      pain. These results show enhanced plasticity in both the motor and somatosensory
      domains in amputees with phantom limb pain.

PMID- 11331391
TI  - Neurotoxic lesions of the lateral nucleus of the amygdala decrease conditioned
      fear but not unconditioned fear of a predator odor: comparison with electrolytic
      lesions.
AB  - Considerable evidence suggests that the lateral (LA) and basal (BA) nuclei of the
      amygdala are sites of plasticity and storage of emotional memory. Recent
      arguments, however, have seriously challenged this view, suggesting that the
      effects of amygdala lesions are attributable to interference with performance of
      fear behavior and not learning and memory. One way to address this controversy is
      to measure the same behavioral response during both conditioned and unconditioned
      fear. This is done in the present study by measuring fear-related freezing
      behavior after electrolytic and neurotoxic lesions of the LA or LA/BA nuclei in
      rats in a contextual fear conditioning paradigm and unconditioned fear to a
      predator odor. Electrolytic LA lesions attenuated post-shock freezing, retention
      test freezing, and freezing to the predator odor trimethylthiazoline (TMT). In
      contrast, excitotoxic NMDA lesions of the LA had no effect on post-shock freezing
      but significantly attenuated retention test freezing. Furthermore, excitotoxic LA
      lesions did not diminish freezing to TMT. Larger excitotoxic lesions that
      included the BA significantly reduced freezing in both the post-shock and
      retention tests but did not appreciably decrease freezing to TMT. The results
      suggest that the LA is important for memory of learned fear but not for
      generation of freezing behavior. In addition, the BA plays a role in freezing in
      conditioned fear situations but not in unconditioned fear. The studies suggest
      that the LA and BA play different roles in fear conditioning, but neither of them
      has a significant role in unconditioned freezing to a predator odor.

PMID- 11331392
TI  - Bidirectional dopamine modulation of GABAergic inhibition in prefrontal cortical
      pyramidal neurons.
AB  - Dopamine regulates the activity of neural networks in the prefrontal cortex that
      process working memory information, but its precise biophysical actions are
      poorly understood. The present study characterized the effects of dopamine on
      GABAergic inputs to prefrontal pyramidal neurons using whole-cell patch-clamp
      recordings in vitro. In most pyramidal cells, dopamine had a temporally biphasic
      effect on evoked IPSCs, producing an initial abrupt decrease in amplitude
      followed by a delayed increase in IPSC amplitude. Using receptor subtype-specific
      agonists and antagonists, we found that the initial abrupt reduction was D2
      receptor-mediated, whereas the late, slower developing enhancement was D1
      receptor-mediated. Linearly combining the effects of the two agonists could
      reproduce the biphasic dopamine effect. Because D1 agonists enhanced spontaneous
      (sIPSCs) but did not affect miniature (mIPSCs) IPSCs, it appears that D1 agonists
      caused larger evoked IPSCs by increasing the intrinsic excitability of
      interneurons and their axons. In contrast, D2 agonists had no effects on sIPSCs
      but did produce a significant reduction in mIPSCs, suggestive of a decrease in
      GABA release probability. In addition, D2 agonists reduced the postsynaptic
      response to a GABA(A) agonist. D1 and D2 receptors therefore regulated GABAergic
      activity in opposite manners and through different mechanisms in prefrontal
      cortex (PFC) pyramidal cells. This bidirectional modulation could have important
      implications for the computational properties of active PFC networks.

PMID- 11331393
TI  - Hypothalamic, metabolic, and behavioral responses to pharmacological inhibition
      of CNS melanocortin signaling in rats.
AB  - The CNS melanocortin (MC) system is implicated as a mediator of the central
      effects of leptin, and reduced activity of the CNS MC system promotes obesity in
      both rodents and humans. Because activation of CNS MC receptors has direct
      effects on autonomic outflow and metabolism, we hypothesized that food intake
      independent mechanisms contribute to development of obesity induced by
      pharmacological blockade of MC receptors in the brain and that changes in
      hypothalamic neuropeptidergic systems known to regulate weight gain [i.e.,
      corticotropin-releasing hormone (CRH), cocaine-amphetamine-related transcript
      (CART), proopiomelanocortin (POMC), and neuropeptide Y (NPY)] would trigger this
      effect. Relative to vehicle-treated controls, third intracerebroventricular
      (i3vt) administration of the MC receptor antagonist SHU9119 to rats for 11 d
      doubled food and water intake (toward the end of treatment) and increased body
      weight ( approximately 14%) and fat content ( approximately 90%), hepatic
      glycogen content ( approximately 40%), and plasma levels of cholesterol (
      approximately 48%), insulin ( approximately 259%), glucagon ( approximately 80%),
      and leptin ( approximately 490%), whereas spontaneous locomotor activity and body
      temperature were reduced. Pair-feeding of i3vt SHU9119-treated animals to i3vt
      vehicle-treated controls normalized plasma levels of insulin, glucagon, and
      hepatic glycogen content, but only partially reversed the elevations of plasma
      cholesterol ( approximately 31%) and leptin ( approximately 104%) and body fat
      content ( approximately 27%). Reductions in body temperature and locomotor
      activity induced by i3vt SHU9119 were not reversed by pair feeding, but rather
      were more pronounced. None of the effects found can be explained by peripheral
      action of the compound. The obesity effects occurred despite a lack in
      neuropeptide expression responses in the neuroanatomical range selected across
      the arcuate (i.e., CART, POMC, and NPY) and paraventricular (i.e., CRH)
      hypothalamus. The results indicate that reduced activity of the CNS MC pathway
      promotes fat deposition via both food intake-dependent and -independent
      mechanisms.

PMID- 11331394
TI  - Coding specificity in cortical microcircuits: a multiple-electrode analysis of
      primate prefrontal cortex.
AB  - Neurons with directional specificities are active in the prefrontal cortex (PFC)
      during tasks that require spatial working memory. Although the coordination of
      neuronal activity in PFC is thought to be maintained by a network of recurrent
      connections, direct physiological evidence regarding such networks is sparse. To
      gain insight into the functional organization of the working memory system in
      vivo, we recorded simultaneously from multiple neurons spaced 0.2-1 mm apart in
      monkeys performing an oculomotor delayed response task. We used cross-correlation
      analysis and characterized the effective connectivity between neurons in relation
      to their spatial and temporal response properties. The majority of narrow (<5
      msec) cross-correlation peaks indicated common input and were most often observed
      between pairs of neurons within 0.3 mm of each other. Neurons recorded at these
      distances represented the full range of spatial locations, suggesting that the
      entire visual hemifield is represented in modules of corresponding dimensions.
      Nearby neurons could be activated in any epoch of the behavioral task (stimulus
      presentation, delay, response). The incidence and strength of cross-correlation,
      however, was highest among cells sharing similar spatial tuning and similar
      temporal profiles of activation across task epochs. The dependence of correlated
      discharge on the functional properties of neurons was observed both when we
      analyzed firing from the task period as well as from baseline fixation. Our
      results suggest that the coding specificity of individual neurons extends to the
      local circuits of which they are part.

PMID- 11331395
TI  - Differential contribution of substance P and neurokinin A to spinal cord
      neurokinin-1 receptor signaling in the rat.
AB  - Although the tachykinins substance P (SP) and neurokinin A (NKA) are coreleased
      from primary afferent nociceptors and act via neurokinin (NK) receptors, their
      differential effects in vivo are not known. Despite pharmacological evidence that
      NKA preferentially binds NK-2 receptors, this receptor is not found in spinal
      cord neurons. Thus, in the present studies, we compared the extent to which SP
      and NKA contribute to spinal nociceptive processing via the NK-1 receptor. We
      found that SP and NKA induce NK-1 receptor internalization with identical dose
      dependence and induce increases in intracellular calcium at the same
      concentrations, suggesting that SP and NKA equally activate the NK-1 receptor. We
      found, however, that the selective NK-1 receptor antagonist GR 205171 blocked NKA
      but not SP-induced NK-1 receptor internalization in the rat spinal cord in vivo
      and in embryonic day 19 rat spinal neurons in vitro. Using this selectivity of GR
      205171 for NKA-induced NK-1 receptor activation, we examined the relative
      contribution of SP and NKA to noxious stimulus-induced activation of spinal NK-1
      receptors. We estimate that NKA contributes to at least 50% of the NK-1 receptor
      activation in lamina I. Under inflammatory conditions, all noxious stimulus
      induced NK-1 receptor internalization in deep dorsal horn neurons was blocked by
      GR 205171, suggesting that it is entirely NKA-mediated. Substance P-mediated NK-1
      receptor internalization was focused at the site of termination of stimulated
      nociceptors but NKA also activated NK-1 receptors at more distant sites. We
      conclude that NKA not only targets the NK-1 receptor but may be a predominant
      pronociceptive primary afferent neurotransmitter.

PMID- 11331396
TI  - Locomotor recovery in spinal cord-injured rats treated with an antibody
      neutralizing the myelin-associated neurite growth inhibitor Nogo-A.
AB  - The limited plastic and regenerative capabilities of axons in the adult mammalian
      CNS can be enhanced by the application of a monoclonal antibody (mAb), IN-1,
      raised against the myelin-associated neurite growth inhibitor Nogo-A. The aim of
      the present study was to investigate the effects of this treatment on the
      functional recovery of adult rats with a dorsal over-hemisection of the spinal
      cord. Directly after injury, half of the animals were implanted with mAb IN-1
      secreting hybridoma cells, whereas the others received cells secreting a control
      antibody (anti-HRP). A broad spectrum of locomotor tests (open field locomotor)
      score, grid walk, misstep withdrawal response, narrow-beam crossing) was used to
      characterize locomotor recovery during the 5 weeks after the injury. In all
      behavioral tests, the recovery in the mAb IN-1-treated group was significantly
      augmented compared with the control antibody-treated rats. EMG recordings of
      flexor and extensor muscles during treadmill walking confirmed the improvement of
      the locomotor pattern in the mAb IN-1-treated rats; step-cycle duration,
      rhythmicity, and coupling of the hindlimbs were significantly improved. No
      differences between the two groups with regard to nociception were observed in
      the tail flick test 5 weeks after the operation. These results indicating
      improved functional recovery suggest that the increased plastic and regenerative
      capabilities of the CNS after Nogo-A neutralization result in a functionally
      meaningful rewiring of the motor systems.

PMID- 11331397
TI  - Susceptibility to kindling and neuronal connections of the anterior claustrum.
AB  - The claustrum has been implicated in the kindling of generalized seizures from
      limbic sites. We examined the susceptibility of the anterior claustrum itself to
      kindling and correlated this with an anatomical investigation of its afferent and
      efferent connections. Electrical stimulation of the anterior claustrum resulted
      in a pattern of rapid kindling with two distinct phases. Early kindling involved
      extremely rapid progression to bilaterally generalized seizures of short
      duration. With repeated daily kindling stimulations, early-phase generalized
      seizures abruptly became more elaborate and prolonged, resembling limbic-type
      seizures as triggered from the amygdala. We suggest that the rapid rate of
      kindling from the anterior claustrum is an indication that the claustrum is
      functionally close to the mechanisms of seizure generalization. In support of our
      hypothesis, we found significant afferent, efferent, and often reciprocal
      connections between the anterior claustrum and areas that have been implicated in
      the generation of generalized seizures, including frontal and motor cortex,
      limbic cortex, amygdala, and endopiriform nucleus. Additional connections were
      found with various other structures, including olfactory areas, nucleus
      accumbens, midline thalamus, and brainstem nuclei including the substantia nigra
      and the dorsal raphe nucleus. The anatomical connections of the anterior
      claustrum are consistent with its very high susceptibility to kindling and
      support the view that the claustrum is part of a forebrain network of structures
      participating in the generalization of seizures.

PMID- 11331398
TI  - A peripheral mechanism for behavioral adaptation to specific "bitter" taste
      stimuli in an insect.
AB  - Animals have evolved several chemosensory systems for detecting potentially
      dangerous foods in the environment. Activation of specific sensory cells within
      these chemosensory systems usually elicits an aversive behavioral response,
      leading to avoidance of the noxious foods. Although this aversive behavioral
      response can be adaptive, there are many instances in which it generates "false
      alarms," causing animals to reject harmless foods. To minimize the number of
      false alarms, animals have evolved a variety of physiological mechanisms for
      selectively adapting their aversive behavioral response to harmless noxious
      compounds. We examined the mechanisms underlying exposure-induced adaptation to
      specific "bitter" compounds in Manduca sexta caterpillars. M. sexta exhibits an
      aversive behavioral response to many plant-derived compounds that taste bitter to
      humans, including caffeine and aristolochic acid. This aversive behavioral
      response is mediated by three pairs of bitter-sensitive taste cells: one responds
      vigorously to aristolochic acid alone, and the other two respond vigorously to
      both caffeine and aristolochic acid. We found that 24 hr of exposure to a
      caffeinated diet desensitized all of the caffeine-responsive taste cells to
      caffeine but not to aristolochic acid. In addition, we found that dietary
      exposure to caffeine adapted the aversive behavioral response of the caterpillar
      to caffeine, but not to aristolochic acid. We propose that the adapted aversive
      response to caffeine was mediated directly by the desensitized taste cells and
      that the adapted aversive response did not generalize to aristolochic acid
      because the signaling pathway for this compound was insulated from that for
      caffeine.

PMID- 11331399
TI  - Reinforcement of early long-term potentiation (early-LTP) in dentate gyrus by
      stimulation of the basolateral amygdala: heterosynaptic induction mechanisms of
      late-LTP.
AB  - The basolateral amygdala (BLA) can influence distinct learning and memory
      formation. Hippocampal long-term potentiation (LTP), the most prominent cellular
      model of memory formation, can be modulated by stimulation of the BLA in its
      induction and early maintenance. However, it is not known how the late
      maintenance of LTP beyond its initial phases might be affected. Behavioral
      stimuli have been shown to result in a reinforcement of a transient early-LTP
      into a lasting potentiation. Here we show that BLA stimulation mimics the
      behavioral effects on early-LTP in freely moving rats when the BLA is activated
      within a time window of 30 min before or after tetanization of the perforant
      path. The reinforcement of LTP was blocked by inhibitors of muscarinergic and
      beta-adrenergic but not dopaminergic receptors and was dependent on translation.
      Through these heterosynaptic associative interactions, hippocampal sensory
      information can be stabilized by amygdaloidal influences.

PMID- 11331400
TI  - Transfer of glutamine between astrocytes and neurons.
AB  - The export of glutamine from astrocytes, and the uptake of glutamine by neurons,
      are integral steps in the glutamate-glutamine cycle, a major pathway for the
      replenishment of neuronal glutamate. We review here the functional and molecular
      identification of the transporters that mediate this transfer. The emerging
      picture of glutamine transfer in adult brain is of a dominant pathway mediated by
      system N transport (SN1) in astrocytes and system A transport (SAT/ATA) in
      neurons. The participating glutamine transporters are functionally and
      structurally related, sharing the following properties: (a) unlike many neutral
      amino acid transporters which have proven to be obligate exchangers, these
      glutamine transporters mediate net substrate transfer energized by coupling to
      ionic gradients; (b) they are sensitive to small pH changes in the physiological
      range; (c) they are susceptible to adaptive and humoral regulation; (d) they are
      related structurally to the AAAP (amino acid and auxin permeases) family of
      transporters. A key difference between SN1 and the SAT/ATA transporters is the
      ready reversibility of glutamine fluxes via SN1 under physiological conditions,
      which allows SN1 both to sustain a glutamine concentration gradient in astrocytes
      and to mediate the net outward flux of glutamine. It is likely that the ASCT2
      transporter, an obligate exchanger of neutral amino acids, displaces the SN1
      transporter as the main carrier of glutamine export in proliferating astrocytes.

PMID- 11331401
TI  - Differential splicing of transcripts encoding the orphanin FQ/nociceptin
      precursor.
AB  - Orphanin FQ or nociceptin (OFQ/N), the heptadecapeptide agonist for the NOP
      receptor, is derived by proteolytic processing from a precursor protein,
      preproOFQ/N. Previous studies have reported alternative splicing between exons 3
      and 4 of the mouse OFQ/N transcript, which, upon translation, would yield
      precursor proteins with different C-termini. Using RT-PCR, we identified similar
      alternative splicing of preproOFQ/N transcripts in humans and rats. In addition,
      we identified two novel human preproOFQ/N splice variants from which exon 2 has
      been excised and which also undergo alternative splicing between exons 3 and 4.
      Exon 2 contains the translational start site for preproOFQ/N and encodes the
      signal peptide sequence. In vitro translation of cRNAs lacking exon 2 yields
      shorter translation products which arise from an alternative initiator methionine
      located within exon 3. The resulting proteins would lack a signal peptide
      sequence, which would likely alter their cellular trafficking and processing.

PMID- 11331402
TI  - A unique spacer domain of synaptotagmin IV is essential for Golgi localization.
AB  - Synaptotagmin (Syt) family members consist of six separate domains: a short amino
      terminus, a single transmembrane domain, a spacer domain, a C2A domain, a C2B
      domain and a short carboxyl (C) terminus. Despite sharing the same domain
      structures, several synaptotagmin isoforms show distinct subcellular
      localization. Syt IV is mainly localized at the Golgi, while Syt I, a possible
      Ca(2+)-sensor for secretory vesicles, is localized at dense-core vesicles and
      synaptic-like microvesicles in PC12 cells. In this study, we sought to identify
      the region responsible for the Golgi localization of Syt IV by immunocytochemical
      and biochemical analyses as a means of defining the distinct subcellular
      localization of the synaptotagmin family. We found that the unique C-terminus of
      the spacer domain (amino acid residues 73-144) between the transmembrane domain
      and the C2A domain is essential for the Golgi localization of Syt IV. In
      addition, the short C-terminus is probably involved in proper folding of the
      protein, especially the C2B domain. Without the C-terminus, Syt IVdeltaC proteins
      are not targeted to the Golgi and seem to colocalize with an endoplasmic
      reticulum (ER) marker (i.e. induce crystalloid ER-like structures). On the basis
      of these results, we propose that the divergent spacer domain among synaptotagmin
      isoforms may contain certain signals that determine the final destination of each
      isoform.

PMID- 11331403
TI  - Expression of KIF3C kinesin during neural development and in vitro neuronal
      differentiation.
AB  - KIF3A, KIF3B and KIF3C are kinesin-related motor subunits of the KIF3 family that
      associate to form the kinesin-II motor complex in which KIF3C and KIF3B are
      alternative partners of KIF3A. We have analysed the expression of Kif3 mRNAs
      during prenatal murine development. Kif3c transcripts are detectable from
      embryonic day 12.5 and persist throughout development both in the CNS and in some
      peripheral ganglia. Comparison of the expression patterns of the Kif3 genes
      revealed that Kif3c and Kif3a mRNAs colocalize in the CNS, while only Kif3a is
      also present outside the CNS. In contrast, Kif3b is detectable in several non
      neural tissues. We have also performed immunocytochemical analyses of the
      developing rat brain and have found the presence of the KIF3C protein in selected
      brain regions and in several fibre systems. Using neuroblastoma cells as an in
      vitro model for neuronal differentiation, we found that retinoic acid stimulated
      the expression of the three Kif3 and the kinesin-associated protein genes,
      although with different time courses. The selective expression of Kif3c in the
      nervous system during embryonic development and its up-regulation during
      neuroblastoma differentiation suggest a role for this motor during maturation of
      neuronal cells.

PMID- 11331404
TI  - Protein kinase C-mediated functional regulation of dopamine transporter is not
      achieved by direct phosphorylation of the dopamine transporter protein.
AB  - Dopaminergic neurotransmission is terminated by the action of the presynaptic
      dopamine transporter (DAT). It mediates Na(+)/Cl(-) -dependent re-uptake of
      extracellular dopamine (DA) into the cell, and is regarded as a major regulatory
      mechanism for synaptic transmission. Previous works have documented that protein
      kinase C (PKC) activator or inhibitor alters DA uptake by DAT, suggesting that
      PKC phosphorylation plays an important regulatory mechanism in DAT function.
      Based on the existence of consensus amino acid sequences for PKC phosphorylation,
      it has been postulated that PKC regulation of DAT is mediated by the direct
      phosphorylation of DAT protein. In this study, we try to discover whether the
      functional regulation of DAT by PKC is due to direct phosphorylation of DAT. The
      PKC null mutant hDAT, where all putative PKC phosphorylation sites are
      eliminated, has been constructed by the replacement of serine/threonine residues
      with glycines. The mutation itself showed no effect on the functional activities
      of DAT. The DA uptake activity of PKC null mutant was equivalent to those of wild
      type hDAT (80-110% of wild-type). Phorbol ester activation of PKC inhibited DA
      uptake of wild-type hDAT by 35%, and staurosphorine blocked the effect of phorbol
      ester on DA uptake. The same phenomena was observed in PKC null mutant DAT,
      although no significant phosphorylation was observed by PKC activation. Confocal
      microscopic analysis using EGFP-fused DAT revealed that the activation of PKC by
      phorbol ester elicited fluorescent DAT to be internalized into the intracellular
      space both in wild-type and PKC null mutant DAT in a similar way. These results
      suggest that PKC-mediated regulation of DAT function is achieved in an indirect
      manner, such as phosphorylation of a mediator protein or activation of a clathrin
      mediated pathway.

PMID- 11331405
TI  - Control of serotonergic neurons in rat brain by dopaminergic receptors outside
      the dorsal raphe nucleus.
AB  - We studied the control of dorsal raphe (DR) serotonergic neurons by dopaminergic
      transmission in rat brain using microdialysis and single unit extracellular
      recordings. Apomorphine (0.5-3.0 mg/kg s.c.) and quinpirole (0.5 mg/kg s.c.)
      increased serotonin (5-HT) output in the DR and (only apomorphine) in striatum.
      These effects were antagonized by 0.3 mg/kg s.c. SCH 23390 (in DR and striatum)
      and 1 mg/kg s.c. raclopride (in DR). 5-HT(1A) receptor blockade potentiated the 5
      HT increase produced by apomorphine in the DR. Apomorphine (50-400 microg/kg
      i.v.) increased the firing rate of most 5-HT neurons, an effect prevented by SCH
      23390 and raclopride. Quinpirole (40-160 microg/kg i.v.) also enhanced the firing
      rate of 5-HT neurons. When applied in the DR, neither drug increased the 5-HT
      output in the DR or striatum. Likewise, micropressure injection of quinpirole
      (0.2-8 pmol) failed to increase the firing rate of 5-HT neurons. In situ
      hybridization showed that the dopamine (DA) D(2) receptor transcript was almost
      absent in the DR and abundant in the substantia nigra (SN) and the periaqueductal
      grey matter (PAG). Using dual probe microdialysis, the application of
      tetrodotoxin or apomorphine in SN significantly increased the DR 5-HT output.
      Thus, the discrepancy between local and systemic effects of dopaminergic agonists
      and the absence of DA D(2) receptor transcript in 5-HT neurons suggest that DA
      D(2) receptors outside the DR control serotonergic activity.

PMID- 11331406
TI  - Protection of intracellular dopamine cytotoxicity by dopamine disposition and
      metabolism factors.
AB  - Dopamine has been hypothesized as a contributing factor for the selective
      degeneration of dopaminergic neurons in Parkinson's disease. However, the
      cytotoxic mechanisms of dopamine and its metabolites remain poorly understood.
      Using a stable aromatic amino acid decarboxylase (AADC) expressing a fibroblast
      cell line, we previously demonstrated a novel, non-oxidative cytotoxicity of
      intracellular dopamine. In this study, we further investigate the roles of
      dopamine metabolism and disposition proteins against intracellular dopamine
      cytotoxicity by co-expressing these factors in AADC-expressing cells. Our results
      indicate that overexpression of the vesicular monoamine transporter and monoamine
      oxidase A-induced protection against intracellular dopamine toxicity, and
      conversely that pharmacological inhibition of these pathways potentiated L-DOPA
      toxicity in catecholaminergic PC12 cells. Macrophage migration inhibitory factor
      and glutathione S-transferase (GST), factors that have recently been shown to be
      involved in dopamine metabolism, also exhibited a strong protective role against
      intracellular dopamine cytotoxicity. Our results support a potential role for non
      oxidative cytoplasmic dopamine toxicity, and imply that disruption in dopamine
      disposition and/or metabolism could underlie the progressive degeneration of
      dopaminergic neurons in Parkinson's disease.

PMID- 11331407
TI  - Roles of fibroblast growth factor 2 during innervation of the avian inner ear.
AB  - The importance of individual members of the fibroblast growth factor gene family
      during innervation of the vertebrate inner ear is not clearly defined. Here we
      address the role of fibroblast growth factor 2 (FGF-2 or basic FGF) during
      development of the chicken inner ear. We found that FGF-2 stimulated survival of
      isolated cochlear and vestibular neurons during distinct phases of inner ear
      innervation. The potential neurotrophic role of FGF-2 was confirmed by its
      expression in the corresponding sensory epithelia and the detection of one of its
      high-affinity receptors in inner ear neurons. Finally, we have analysed the
      potential of the amplicon system based on defective herpes simplex virus type 1
      (HSV-1) vectors to express FGF-2 in cochlear neurons. Overexpression of FGF-2 in
      cochlear neurons resulted in neuronal differentiation demonstrating the presence
      of biologically active growth factor. This study underlines the potential of FGF
      2 to control innervation and development of sensory epithelia in the avian inner
      ear. Furthermore, amplicon vectors may provide a useful tool to analyse gene
      function in isolated neurons of the vertebrate inner ear.

PMID- 11331408
TI  - Chronic valproate treatment decreases the in vivo turnover of arachidonic acid in
      brain phospholipids: a possible common effect of mood stabilizers.
AB  - Both (Li(+)) and valproic acid (VPA) are effective in treating bipolar disorder,
      but the pathway by which either works, and whether it is common to both drugs, is
      not agreed upon. We recently reported, using an in vivo fatty acid model, that
      Li(+) reduces the turnover rate of the second messenger arachidonic acid (AA) by
      80% in brain phospholipids of the awake rat, without changing turnover rates of
      docosahexaenoic or palmitic acid. Reduced AA turnover was accompanied by down
      regulation of gene expression and protein levels of an AA-specific cytosolic
      phospholipase A(2) (cPLA(2)). To see if VPA had the same effect on AA turnover,
      we used our in vivo fatty acid model in rats chronically administered VPA (200
      mg/kg, i.p. for 30 days). Like Li(+), VPA treatment significantly decreased AA
      turnover within brain phospholipids (by 28-33%), although it had no effect on
      cPLA(2) protein levels. Thus, both mood stabilizers, Li(+) and VPA have a common
      action in reducing AA turnover in brain phospholipids, albeit by different
      mechanisms.

PMID- 11331409
TI  - Estradiol protects against ATP depletion, mitochondrial membrane potential
      decline and the generation of reactive oxygen species induced by 3
      nitroproprionic acid in SK-N-SH human neuroblastoma cells.
AB  - Mitochondria are recognized as modulators of neuronal viability during ischemia,
      hypoxia and toxic chemical exposure, wherein mitochondria dysfunction leading to
      ATP depletion may be a common pathway of cell death. Estrogens have been reported
      to be neuroprotective and proposed to play a role in the modulation of cerebral
      energy/glucose metabolism. To address the involvement of 17beta-estradiol
      preservation of mitochondrial function, we examined various markers of
      mitochondrial activity in human SK-N-SH neuroblastoma cells exposed to 3
      nitroproprionic acid (3-NPA), a succinate dehydrogenase inhibitor which uncouples
      oxidative phosphorylation. 3-NPA (10 mM) significantly increased ATP levels at 2
      h then caused a 40% and a 50% decrease in ATP levels from baseline when treated
      for 12 h and 24 h, respectively. 3-NPA also induced significant increases in
      levels of cellular hydrogen peroxide and peroxynitrite at 2 h and a 60% decrease
      in mitochondrial membrane potential (MMP) at 12 h exposure. 17beta-Estradiol
      (17beta-E(2)) pretreatment restored the ATP level back to 80% at 12 h of that in
      control cells treated with 3-NPA but without E(2), blunted the effect of 3-NPA on
      MMP and reactive oxygen species levels. The present study indicates that 17beta
      E(2) can preserve mitochondrial function in the face of inhibition of oxidative
      phosphorylation.

PMID- 11331410
TI  - Amino acid determinants for NMDA receptor inhibition by conantokin-T.
AB  - Several derivatives of conantokin-T (con-T), a naturally occurring, gamma
      carboxyglutamate (Gla)-containing peptide with NMDA receptor (NMDAR) antagonist
      properties, were synthesized and evaluated for their ability to displace [(3)H]MK
      801 from adult rat forebrain membranes. Analyses of progressive C-terminal
      truncation analogs of the parent 21-mer revealed gradual losses in activity with
      decreased chain length. In this series, con-T[1-8] was identified as the shortest
      variant capable of manifesting inhibitory activity (< 1% of the parent peptide).
      Ala substitution studies of individual residues identified Gly1, Gla3, Met8 and
      Leu12 as important for activity, while Glu2, Gla4 and Tyr5 were shown to be
      essential in this regard. The effect of side-chain length and charge in the N
      terminal region was probed by single amino acid replacements. No correlation was
      observed between potencies and circular dichroism-derived helical contents of the
      con-T derivatives. Further elaboration of structure-function relationships in con
      T was effected through the design and synthesis of helically constrained and
      destabilized analogs. The results of the current study were compared with those
      of a previous investigation on con-G, a related conantokin. Substantial
      differences in activity requirements were noted between the peptides,
      particularly in the C-terminal regions. Chimeras of con-T and con-G were
      generated and revealed virtually no interchangeability of residues between these
      two peptides. Finally, single amino acid substitutions that resulted in analogs
      with enhanced inhibitory properties were combined to yield superior conantokin
      based NMDAR inhibitors.

PMID- 11331411
TI  - Protein kinase C-mediated down-regulation of beta(2)-adrenergic receptor and gene
      expression in rat C6 glioma cells.
AB  - We investigated the regulation of beta(2)-adrenergic receptors (beta(2)AR) by
      protein kinase C (PKC) in rat C6 glioma cells at the levels of receptor activity,
      protein expression and gene expression. Cells exposed to 4beta-phorbol-12
      myristate-13-acetate (PMA), a potent activator of PKC, exhibited a time- and
      concentration-dependent decrease in beta(2)AR binding activity. Maximum down
      regulation was approximately 50% by 24 h and western blot analysis revealed a
      parallel decrease in beta(2)AR protein. In addition, PMA treatment resulted in an
      acute desensitization of beta(2)AR-stimulated cyclic AMP response prior to any
      reduction in receptor levels. PMA exposure also affected steady-state beta(2)AR
      mRNA levels in a time-dependent, biphasic manner. During the first 4 h, levels
      decreased by approximately 60% and then slowly recovered to approximately 75% of
      control by 24 h. As the reduction in receptor mRNA was not due to a decrease in
      its stability, we examined beta(2)AR gene transcription by nuclear run-on assays.
      Transcriptional activity in nuclei from C6 cells treated with PMA for 2 h was
      reduced by 70% compared to controls. Thus PKC can regulate beta(2)AR at least two
      levels: the first being an acute desensitization of receptor function, and the
      second being a more prolonged repression of receptor gene transcription that in
      turn results in decreased receptor expression.

PMID- 11331412
TI  - Dehydroepiandrosterone inhibits lipopolysaccharide-induced nitric oxide
      production in BV-2 microglia.
AB  - Levels of dehydroepiandrosterone (DHEA) and its sulfated derivative (DHEAS)
      decline during aging and reach even lower levels in Alzheimer's disease (AD).
      DHEA is known to exhibit a variety of functional activities in the CNS, including
      an increase of memory and learning, neurotrophic and neuroprotective effects, and
      the reduction of risk of age-related neurodegenerative disorders. However, the
      influence of DHEA on the immune functions of glial cells is poorly understood. In
      this study, we investigated the effect of DHEA on activated glia. The production
      of inducible nitric oxide synthase (iNOS) was studied in lipopolysaccharide (LPS)
      stimulated BV-2 microglia, as a model of glial activation. The results showed
      that DHEA but not DHEAS significantly inhibited the production of nitrite in the
      LPS-stimulated BV-2 cell cultures. Pretreatment of BV-2 cells with DHEA reduced
      the LPS-induced iNOS mRNA and protein levels in a dose-dependent manner. The LPS
      induced iNOS activity in BV-2 cells was decreased by the exposure of 100 microM
      DHEA. Moreover, DHEA suppressed iNOS gene expression in LPS-stimulated BV-2 cells
      did not require de novo synthesis of new proteins or destabilize of iNOS mRNA.
      Since DHEA is biosynthesized by astrocytes and neurons, our findings suggest that
      it might have an important regulatory function on microglia.

PMID- 11331413
TI  - Protein kinase C regulation of dopamine transporter initiated by nicotinic
      receptor activation in slices of rat prefrontal cortex.
AB  - We previously reported that activation of nicotinic receptors causes an
      enhancement in amphetamine-stimulated release of dopamine via its transporter
      from slices of prefrontal cortex, but no such enhancement of release from slices
      of nucleus accumbens or striatum. The nicotinic receptors mediating the
      enhancement most likely contain alpha4 and beta2 subunits based upon
      pharmacological characterization. In this study, we sought to characterize the
      second messenger systems associated with the nicotine-mediated response. Sodium
      channel involvement was confirmed by the observation that tetrodotoxin blocked
      nicotine-mediated enhancement, whereas veratridine or elevated K(+) mimicked the
      enhancement seen with nicotine. Inclusion of EGTA blocked nicotine-mediated
      enhancement, suggesting that, even though no exogenous Ca(2+) was added,
      endogenous stores were required for the enhancement. The enhancement by nicotine
      was also abolished by the L-type voltage-dependent calcium channel (VDCC)
      antagonist nitrendipine, but not by the N-type VDCC antagonist omega-conotoxin
      GVIA. Finally, inhibition of protein kinase C also abolished the nicotine
      mediated enhancement of amphetamine-stimulated dopamine release, whereas
      inhibitors of Ca(2+)/calmodulin kinase II did not. These findings establish that
      nicotine can exert selective effects on dopamine transporter activity in
      prefrontal cortex, an area involved in cognition and learning.

PMID- 11331414
TI  - CEP-1347/KT-7515, an inhibitor of SAPK/JNK pathway activation, promotes survival
      and blocks multiple events associated with Abeta-induced cortical neuron
      apoptosis.
AB  - Although the mechanism of neuronal death in Alzheimer's disease (AD) has yet to
      be elucidated, a putative role for c-jun in this process has emerged. Thus, it
      was of interest to delineate signal transduction pathway(s) which regulate the
      transcriptional activity of c-jun, and relate these to alternate gene inductions
      and biochemical processes associated with beta-amyloid (Abeta) treatment. In this
      regard, the survival promoting activity of CEP-1347, an inhibitor of the stress
      activated/c-jun N-terminal (SAPK/JNK) kinase pathway, was evaluated against Abeta
      induced cortical neuron death in vitro. Moreover, CEP-1347 was used as a
      pharmacologic probe to associate multiple biochemical events with Abeta-induced
      activation of the SAPK/JNK pathway. CEP-1347 promoted survival and blocked Abeta
      induced activation of JNK kinase (MKK4, also known as MEK-4, JNKK and SEK1) as
      well as other downstream events associated with JNK pathway activation. CEP-1347
      also blocked Abeta-induction of cyclin D1 and DP5 genes and blocked Abeta-induced
      increases in cytoplasmic cytochrome c, caspase 3-like activity and calpain
      activation. The critical time window for cell death blockade by CEP-1347 resided
      within the peak of Abeta-induced MKK4 activation, thus defining this point as the
      most upstream event correlated to its survival-promoting activity. Together,
      these data link the SAPK/JNK pathway and multiple biochemical events associated
      with Abeta-induced neuronal death and further delineate the point of CEP-1347
      interception within this signal transduction cascade.

PMID- 11331415
TI  - Nerve growth factor induces P2X(3) expression in sensory neurons.
AB  - Glial cell line-derived neurotrophic factor (GDNF) and nerve growth factor (NGF)
      are neuroprotective for subpopulations of sensory neurons and thus are candidates
      for pain treatment. However, delivering these factors to damaged neurons will
      invariably result in undamaged systems also being treated, with possible
      consequences for sensory processing. In sensory neurons the purinergic receptor
      P2X(3) is found predominantly in GDNF-sensitive nociceptors. ATP signalling via
      the P2X(3) receptor may contribute to pathological pain, suggesting an important
      role for this receptor in regulating nociceptive function. We therefore
      investigated the effects of intrathecal GDNF or NGF on P2X(3) expression in adult
      rat spinal cord and dorsal root ganglia (DRG). In control spinal cords, P2X(3)
      expression was restricted to a narrow band of primary afferent terminals within
      inner lamina II (II(i)). Glial cell line-derived neurotrophic factor treatment
      increased P2X(3) immunoreactivity within lamina II(i) but not elsewhere in the
      cord. Nerve growth factor treatment, however, induced novel P2X(3) expression,
      with intense immunoreactivity in axons projecting to lamina I and outer lamina II
      and to the ventro-medial afferent bundle beneath the central canal. In the normal
      DRG, we found a greater proportion of P2X(3)-positive neurons at cervical levels,
      many of which were large-diameter and calcitonin gene-related peptide-positive.
      In both cervical and lumbar DRG, the number of P2X(3)-positive cells increased
      following GDNF or NGF treatment. De novo expression of P2X(3) in NGF-sensitive
      nociceptors may contribute to chronic inflammatory pain.

PMID- 11331416
TI  - UTP evokes noradrenaline release from rat sympathetic neurons by activation of
      protein kinase C.
AB  - The pathway involved in UTP-evoked noradrenaline release was investigated in
      cultures of rat superior cervical ganglia. Northern blots revealed an age-related
      increase in levels of mRNA for P2Y6 receptors in cultures obtained at postnatal
      days 1 and 5, respectively, but no change in transcripts for P2Y1 and P2Y2.
      Likewise, UTP-evoked overflow of previously incorporated [(3)H]noradrenaline was
      six-fold higher in neurons obtained at postanatal day 5. Various protein kinase C
      inhibitors diminished UTP-, but not electrically, induced tritium overflow by >
      70%, as did down-regulation of protein kinase C by 24 h exposure to phorbol
      ester. beta-Phorbol-12,13-dibutyrate and dioctanoylglycerol caused concentration
      dependent increases in [(3)H] outflow of up to 6% of total radioactivity, and the
      secretagogue actions of these agents were reduced in the presence of protein
      kinase C inhibitors and in neurons pretreated with phorbol ester. Overflow evoked
      by dioctanoylglycerol was attenuated in the absence of extracellular Ca(2+) and
      in the presence of tetrodotoxin or Cd(2+). In addition to triggering tritium
      overflow, UTP reduced currents through muscarinic K(+) channels which, however,
      were not affected by phorbol esters. This action of UTP was not altered by
      protein kinase C inhibitors. These results indicate that P2Y6 receptors mediate
      UTP-evoked noradrenaline release from rat sympathetic neurons via activation of
      protein kinase C, but not inhibition of K(M) channels.

PMID- 11331417
TI  - Caspase-2 activation is redundant during seizure-induced neuronal death.
AB  - Seizure-induced neuronal death may be under the control of the caspase family of
      cell death proteases. We examined the role of caspase-2 in a model of focally
      evoked limbic seizures with continuous EEG recording. Seizures were elicited by
      microinjection of kainic acid into the amygdala of the rat and terminated after
      40 min by diazepam. Caspase-2 was constitutively present in brain, mostly within
      neurons, and was detected in both cytoplasm and nucleus. Cleaved caspase-2 (12
      kDa) was detected immediately following seizure termination within injured
      ipsilateral hippocampus, contiguous with increased Val-Asp-Val-Ala-Asp (VDVADase)
      activity, a putative measure of activated caspase-2. Expression of receptor
      interacting protein (RIP)-associated Ich-1-homologous protein with death domain
      (RAIDD) was increased following seizures, whereas expression of RIP and tumor
      necrosis factor receptor associated protein with death domain (TRADD), other
      components thought to be linked to the caspase-2 activation and signaling
      mechanism, were unchanged. Intracerebroventricular administration of z-VDVAD
      fluoromethyl ketone blocked seizure-induced caspase-2 activity but did not alter
      caspase-8 activity and failed to affect DNA fragmentation or neuronal death.
      These data support activation of caspase-2 following seizures but suggest that
      parallel caspase pathways may circumvent deficits in caspase-2 function to
      complete the cell death process.

PMID- 11331418
TI  - Identification of a novel member of the T1R family of putative taste receptors.
AB  - In the gustatory system, the recognition of sugars, amino acids and bitter
      tasting compounds is the function of specialized G protein-coupled receptors.
      Recently, two members of novel subfamily of G protein-coupled receptors were
      proposed to function as taste receptors based on their specific expression in
      taste receptor cells. Here, we report the identification of a third member, T1R3,
      of this family of receptors. T1R3 maps near the telomere of mouse chromosome 4
      rendering it a candidate for the Sac locus, a primary determinant of sweet
      preference in mice. Consistent with its candidacy for the Sac locus, T1R3
      displays taste receptor cell-specific expression. In addition, taster and non
      taster strains of mouse harbor different alleles of T1R3.

PMID- 11331419
TI  - Antibodies against c-Jun N-terminal peptide cross-react with neo-epitopes
      emerging after caspase-mediated proteolysis during apoptosis.
AB  - In previous studies it has been shown that neural cells undergoing programmed
      cell death display strongly positive cytoplasmic immunoreactivity to polyclonal
      antibodies directed against a c-Jun N-terminal peptide. It was later found that c
      Jun-like immunoreactivity in apoptosis was due to cross-reactivity with proteins
      other than c-JUN: We have analysed the biochemical counterpart of this property
      in neuroblastoma cell lines treated to induce apoptosis. Using the c-Jun/sc-45
      antibody, several bands with apparent molecular masses distinct from c-Jun were
      detected in extracts in parallel with both the degree of apoptosis and the
      appearance of the cytoplasmic signal after immunostaining. c-Jun/sc-45
      immunostaining was prevented by caspase inhibitors and did not require de novo
      protein synthesis. One of the antigens recognized by the c-Jun/sc-45 antibody was
      identified as seryl-tRNA synthetase. We provide evidence that seryl-tRNA
      synthetase is a substrate of caspase-3 in vitro and that the digested form turns
      highly immunoreactive towards the antibody. A carboxy-terminus epitope of the
      protein that constitutes a consensus site for caspase-3 is involved in c-Jun/sc
      45 recognition. This epitope shares some amino acids with the peptide used as the
      immunogen and this could explain the cross-reactivity observed. In conclusion, we
      demonstrate here that cytoplasmic c-Jun/sc-45-like immunoreactivity specific to
      apoptosis is due to post-translational changes which occur in seryl-tRNA
      synthetase and probably also in other proteins as a consequence of caspase
      mediated proteolysis.

PMID- 11331420
TI  - Reduced activation and expression of ERK1/2 MAP kinase in the post-mortem brain
      of depressed suicide subjects.
AB  - The extracellular regulated kinases (ERK) 1 and ERK2 are members of mitogen
      activated protein (MAP) kinase family that play an important role in transducing
      extracellular signals to the nucleus and have been implicated in a broad spectrum
      of biological responses. To test the hypothesis that MAP kinases may be involved
      in depression, we examined the activation of p44/42 MAP kinase and expression of
      ERK1 and ERK2 in the post-mortem brain tissue obtained from non-psychiatric
      control subjects (n = 11) and age- and the post-mortem interval-matched depressed
      suicide subjects (n = 11). We observed that p44/42 MAP kinase activity was
      significantly decreased in the prefrontal cortical areas (Brodmann's areas 8, 9
      and 10) and the hippocampus of depressed suicide subjects without any change in
      the cerebellum. This decrease was associated with a decrease in mRNA and protein
      levels of ERK1 and ERK2. In addition, the expression of MAP kinase phosphatase
      (MKP)2, a 'dual function' ERK1/2 phosphatase, was increased in the prefrontal
      cortex and hippocampus. These studies suggest that p44/42 MAP kinases are less
      activated in the post-mortem brain of depressed suicide subjects and this may be
      because of reduced expression of ERK1/2 and increased expression of MKP2. Given
      the role of MAP kinases in various physiological functions and gene expression,
      alterations in p44/42 MAP kinase activation and expression of ERK1/2 may
      contribute significantly to the pathophysiology of depressive disorders.

PMID- 11331422
TI  - The transcriptional regulator Yin Yang 1 activates the myelin PLP gene.
AB  - Inauguration of the myelin program in developing oligodendrocytes requires the
      activation of those genes that encode the myelin proteins and the enzymes
      responsible for the synthesis and degradation of myelin lipids. An activator of
      the most abundantly expressed myelin protein, proteolipid protein (PLP), has been
      identified in a yeast one-hybrid system. The ubiquitously expressed zinc finger
      protein Yin Yang 1 (YY1) recognizes the myelin PLP promoter in vitro and in vivo.
      When overexpressed in an oligodendrocyte cell line, YY1 enhances transcription of
      the PLP promoter. A truncated version of YY1 that includes only the four zinc
      finger domains has little effect. The binding site for YY1 in the PLP promoter
      (site 3) fits the YY1 consensus site and DNA-protein complexes containing site 3
      can be supershifted with an antibody directed against YY1 protein. Moreover,
      oligonucleotides with a mutated version of the PLP promoter site 3 are unable to
      bind to nuclear proteins or to compete for binding in a gel shift system.
      Finally, mutation of this site greatly reduces the activity of a 1-kb PLP
      promoter region in transfected glial cells. Our results suggest that PLP is a
      target gene for the transcriptional regulator YY1. This versatile transcription
      factor and nuclear matrix protein may boost transcription of the PLP gene to meet
      the demands of actively myelinating oligodendrocytes.

PMID- 11331421
TI  - Interaction of alpha-synuclein and synphilin-1: effect of Parkinson's disease
      associated mutations.
AB  - alpha-Synuclein is a major component of Lewy bodies, a neuropathological feature
      of Parkinson's disease. Two alpha-synuclein mutations, Ala53Thr and Ala30Pro, are
      associated with early onset, familial forms of the disease. Recently, synphilin
      1, a protein found to interact with alpha-synuclein by yeast two hybrid
      techniques, was detected in Lewy bodies. In this study we report the interaction
      of alpha-synuclein and synphilin-1 in human neuroglioma cells using a sensitive
      fluorescence resonance energy transfer technique. We demonstrate that the C
      terminus of alpha-synuclein is closely associated with the C-terminus of
      synphilin-1. A weak interaction occurs between the N-terminus of alpha-synuclein
      and synphilin-1. The familial Parkinson's disease associated mutations of alpha
      synuclein (Ala53Thr and Ala30Pro) also demonstrate a strong interaction between
      their C-terminal regions and synphilin-1. However, compared with wild-type alpha
      synuclein, significantly less energy transfer occurs between the C-terminus of
      Ala53Thr alpha-synuclein and synphilin-1, suggesting that the Ala53Thr mutation
      alters the conformation of alpha-synuclein in relation to synphilin-1.

PMID- 11331423
TI  - Effects of protracted nicotine exposure and withdrawal on the expression and
      phosphorylation of the CREB gene transcription factor in rat brain.
AB  - Addiction to nicotine may result in molecular adaptations in the neurocircuitry
      of specific brain structures via changes in the cyclic AMP-responsive element
      binding protein (CREB)-dependent gene transcription program. We therefore
      investigated the effects of chronic nicotine exposure and its withdrawal on CREB
      and phosphorylated CREB (p-CREB) protein levels in the rat brain. We report here
      that chronic nicotine exposure (1-h withdrawal) had no effect on the expression
      of CREB and p-CREB in the rat cortex and amygdala. On the other hand, decreases
      in the expression of CREB protein and phosphorylation of CREB occur in the
      cingulate gyrus, and in the parietal and the piriform but not in the frontal
      cortex during nicotine withdrawal (18 h) after nicotine exposure. It was also
      observed that CREB and p-CREB protein levels were significantly decreased in the
      medial and basolateral, but not in the central amygdala during nicotine
      withdrawal (18 h) after chronic nicotine exposure. Furthermore, it was found that
      nicotine withdrawal (18 h) after chronic nicotine exposure leads to decreased CRE
      DNA binding without modulating cAMP-dependent protein kinase A activity in the
      cortex and the amygdala of rats. In addition, chronic nicotine treatment produced
      anxiolytic effects whereas nicotine withdrawal (18 h) produced anxiety in rats as
      measured by the elevated plus-maze test. These results provide the first evidence
      that decreased CREB activity and/or expression in specific cortical and
      amygdaloid brain structures may be involved in the underlying molecular
      mechanisms of nicotine dependence.

PMID- 11331424
TI  - Amyloid beta peptides mediate hypoxic augmentation of Ca(2+) channels.
AB  - Clinical studies indicate that neurodegeneration caused by Alzheimer's amyloid
      beta peptide (AbetaP) formation can be triggered or induced by prolonged
      (chronic) hypoxia. Here, we demonstrate that 24-h culture of PC12 cells in 10%
      O(2) leads to induction of a Cd(2+)-resistant Ca(2+) influx pathway and selective
      potentiation of L-type Ca(2+) current. Both effects were suppressed or prevented
      by a monoclonal antibody raised against the N'-terminus of AbetaP, and were fully
      mimicked by AbetaP(1-40 and) AbetaP(1-42), but not by AbetaP(40-1). Potentiation
      of L-type currents was also induced by exposure to AbetaP(25-35). Our results
      indicate that hypoxia induces enhancement of Ca(2+) channels, which is mediated
      by increased AbetaP formation.

PMID- 11331425
TI  - Cannabinoids activate p38 mitogen-activated protein kinases through CB1 receptors
      in hippocampus.
AB  - Cannabinoid receptors (CB1-R) are the target of a novel class of neuromodulators,
      the endocannabinoids. Yet, their signalling mechanisms in adult brain are poorly
      understood. We report that, in rat and mouse hippocampal slices, anandamide and 2
      arachidonoylglycerol, synthetic cannabinoids, and delta(9)-tetrahydrocannabinol
      activated p38 mitogen-activated protein kinases (MAPK), but not c-Jun N-terminal
      kinase (JNK). In contrast, lysophosphatidic acid (LPA), a lipid messenger acting
      on different receptors, increased both p38-MAPK and JNK phosphorylation. The
      effects of cannabinoids on p38-MAPK were mediated through activation of CB1-R
      because they were blocked in the presence of SR 141716 A and absent in CB1-R
      knockout mice, two conditions that did not alter the effects of LPA. The
      activation of p38-MAPK by cannabinoids was insensitive to inhibitors of SRC:
      These results provide new insights into the cellular mechanisms by which
      cannabinoids exert their effects in hippocampus.

PMID- 11331426
TI  - Defining health-related obesity in prepubertal children.
AB  - OBJECTIVE: The purpose of this study was to develop percentage of fat and waist
      circumference cut-points in prepubertal children with the intention of defining
      obesity associated with cardiovascular disease (CVD) risk. RESEARCH METHODS AND
      PROCEDURES: A cross-sectional analysis of 87 prepubertal children aged 4 to 11
      years was used. Percentage of body fat was determined by DXA. Waist circumference
      was measured to the nearest millimeter. Receiver Operating Characteristic
      analyses of percentage of fat and waist circumference were used to develop cut
      points for individuals with adverse levels of CVD risk factors. RESULTS: The risk
      factors selected for analyses (i.e., fasting insulin, high-density lipoprotein
      cholesterol, low-density lipoprotein cholesterol, triglycerides, and total
      cholesterol/high-density lipoprotein cholesterol) were significantly related to
      percentage of body fat and waist circumference. Likelihood ratios were used to
      identify percentage of fat and waist circumference cut-points associated with
      adverse cardiovascular risk profiles. Two cut-points, an upper cut-point of 33%
      body fat and a lower cut-point of 20% body fat, were derived. Waist circumference
      cut-points indicative of adverse and normal risk-factor profiles were 71 cm and
      61 cm, respectively. DISCUSSION: The data indicate that children with > or =33%
      body fat and children with a waist circumference > or =71 cm were more likely to
      possess an adverse CVD risk-factor profile than a normal risk-factor profile. The
      likelihood of children with < 20% body fat or a waist circumference < 61 cm
      possessing an adverse CVD risk-factor profile as opposed to a normal risk-factor
      profile was small. The cut-points describe an adequate health-related definition
      of childhood obesity.

PMID- 11331427
TI  - Effect of insulin and energy restriction on the thermic effect of protein in type
      2 diabetes mellitus.
AB  - OBJECTIVE: The objective of this study was to test whether the thermic effect of
      oral protein is blunted in poorly controlled type 2 diabetes and is corrected by
      normalization of glycemia with insulin and 28 days of a very-low-energy diet.
      RESEARCH METHODS AND PROCEDURES: Resting energy expenditure (REE) and the thermic
      effect of 90 g of oral protein were measured, using indirect calorimetry, in nine
      (five women and four men) obese diabetic people [weight, 108 +/- 10 kg; waist
      circumference, 123 +/- 8 cm; body mass index, 40 +/- 3 kg/m(2)] who were
      hyperglycemic on day 8 or euglycemic with insulin on day 16 of a weight
      maintaining diet and euglycemic on day 28 of a very low energy diet (VLED).
      Results were compared with those of seven (six women and one man) weight- and
      body mass index-matched obese nondiabetic subjects with a waist circumference of
      111 +/- 6 cm. Substrates and hormonal responses were determined concurrently.
      RESULTS: Fasting glucose was normalized in the diabetic subjects with insulin
      from day 9 of VLED onward. Weight decreased in both groups by 9.9 +/- 0.9 kg with
      VLED. REE was 8 +/- 2% lower with insulin treatment and decreased by another 14
      +/- 3% with VLED in the diabetic and by 15 +/- 1% in the nondiabetic subjects by
      week 4. After the protein meal, the thermic response was significantly (p < 0.05)
      less with hyperglycemia than with insulin-induced euglycemia, as percentage above
      REE (15.3 +/- 1.4 compared with 21.2 +/- 1.5%), as percentage of the energy
      content of the meal (19.5 +/- 1.5 compared with 25.2 +/- 1.7%), as kilocalories
      per 405 minutes (86 +/- 5 compared with 110 +/- 7), and less than in nondiabetic
      obese controls (21.0 +/- 2.2% above REE, 24.4 +/- 1.7% of energy of meal). After
      the VLED, the thermic effect of protein was significantly higher in both groups
      only as percentage above REE. The initial glucagon response was greater with
      hyperglycemia compared with euglycemia and post-VLED but not compared with the
      nondiabetic subjects. Hyperglycemia was associated with 21 +/- 4% greater urinary
      urea nitrogen excretion and urinary glucose losses of 134 +/- 50 mmol/d.
      DISCUSSION: This study shows a blunted thermic effect of protein in obese
      hyperglycemic type 2 diabetic subjects compared with matched nondiabetic subjects
      that can be corrected with insulin- or energy restriction-induced euglycemia.

PMID- 11331428
TI  - Influence of sibutramine on energy expenditure in African American women.
AB  - OBJECTIVE: African American women have a high prevalence of obesity, which
      partially may be explained by their lower rates of resting energy expenditure
      (REE). The aim of this study was to examine the influence of acute sibutramine
      administration on REE and post-exercise energy expenditure in African American
      women. RESEARCH METHODS AND PROCEDURES: A total of 15 premenopausal, African
      American women (age, 29 +/- 5 years; body fat, 38 +/- 7%) completed a randomized,
      double-blind cross-over design with a 30-mg ingestion of sibutramine or a
      placebo. Each trial was completed a month apart in the follicular phase and
      included a 30-minute measurement of REE 2.5 hours after sibutramine or placebo
      administration. This was followed by 40 minutes of cycling at approximately 70%
      of peak aerobic capacity and a subsequent 2-hour measurement of post-cycling
      energy expenditure. RESULTS: There was no difference (p > 0.05) in REE (23.70 +/-
      2.81 vs. 23.69 +/- 2.95 kcal/30 min), exercise oxygen consumption (1.22 +/- 0.15
      vs. 1.25 +/- 0.15 liter/min), and post-cycling energy expenditure (104.2 +/- 12.7
      vs. 104.9 +/- 11.4 kcal/120 min) between the sibutramine and placebo trials,
      respectively. Cycling heart rate was significantly higher (p = 0.01) during the
      sibutramine (158 +/- 14 beats/min) vs. placebo (150 +/- 12 beats/min) trials.
      DISCUSSION: These data demonstrate that acute sibutramine ingestion does not
      increase REE or post-exercise energy expenditures but does increase exercising
      heart rate in overweight African American women. Sibutramine may, therefore,
      impact weight loss through energy intake and not energy expenditure mechanisms.

PMID- 11331429
TI  - Weight loss and gender: an examination of physician attitudes.
AB  - OBJECTIVE: The purpose of this study was to investigate physician attitudes
      toward the treatment of overweight and obese individuals and to evaluate
      potential gender differences in treatment recommendations. RESEARCH METHODS AND
      PROCEDURES: A survey describing several hypothetical patients was sent to 700
      randomly selected physicians; 209 (29.9%) returned the survey. Two versions of
      the questionnaire (one for men and one for women) described three hypothetical
      patients at three levels of body mass index (BMI) (32, 28, and 25 kg/m(2)). One
      half of the physicians received a version of the questionnaire describing the
      patients as women, and one-half received a version describing the patients as
      men. Respondents answered questions about attitudes toward treatment and specific
      interventions and referrals they would view as appropriate. RESULTS: Physicians
      were more likely to encourage women with a BMI of 25 kg/m(2) to lose weight than
      men with the same BMI, and indicated that they would suggest more treatment
      referrals for women than men. Men with a BMI of 32 kg/m(2) were more likely to be
      encouraged to lose weight than women with the identical BMI. Physicians were more
      likely to encourage weight loss and see treatment referrals as appropriate for
      patients with higher BMIS: DISCUSSION: This study indicates that physicians treat
      male and female patients differently, with physicians more likely to encourage
      weight loss and provide referrals for women with a BMI of 25 kg/m(2) than for men
      with an identical BMI and less likely to encourage weight loss for women than men
      with a BMI of 32 kg/m(2).

PMID- 11331430
TI  - Night eating syndrome is associated with depression, low self-esteem, reduced
      daytime hunger, and less weight loss in obese outpatients.
AB  - OBJECTIVE: The objective of this study was to assess the relationship between the
      night eating syndrome (NES), measures of depression and self-esteem, test meal
      intake, and weight loss in obese participants. RESEARCH METHODS AND PROCEDURES:
      The study included 76 overweight (body mass index = 36.7 +/- 6.5 SD) outpatients
      (53 women and 23 men; aged 43.5 +/- 9.5 years) entering a weight loss program.
      They completed a Night Eating Questionnaire, the Zung Depression Inventory, and
      the Rosenberg Self-Esteem SCALE: Based on criteria by Stunkard et al. (Stunkard
      A, Berkowitz R, Wadden T, Tanrikut C, Reiss E, Young L. Binge eating disorder and
      the night eating syndrome. Int J Obes Relat Metab DISORD: 1996;20:1-6),
      participants had NES if they reported: (1) skipping breakfast > or =4 d/wk,
      interpreted as morning anorexia; (2) consuming more than 50% of total daily
      calories after 7 PM; and (3) difficulty falling asleep or staying asleep > or =4
      d/wk. Eleven (14%) participants met the criteria for NES. After an 8-hour fast,
      all participants ingested a nutritionally complete liquid meal through a straw
      from a large opaque cooler until extremely full. They also completed ratings of
      hunger and fullness before and after this meal. RESULTS: Night eaters had higher
      depression (p = 0.04), lower self-esteem (p = 0.003), and less hunger (p =
      0.005), and a trend for more fullness (p = 0.06) before the daytime test meal
      than the others. However, there were no significant differences in test-meal
      intake between groups. Nevertheless, test-meal intake was greater later in the
      day only for the night eaters (p = 0.01). Over a 1-month period, the night eaters
      lost less weight (4.4 +/- 3.2 kg) than the others (7.3 +/- 3.2 kg; p = 0.04),
      after controlling for body mass index. DISCUSSION: NES is a syndrome with
      distinct psychopathology and increased food intake later in the day, both of
      which may contribute to poorer weight loss outcome. NES criteria need to be
      better quantified and NES deserves consideration as a diagnostic eating disorder.

PMID- 11331431
TI  - Evolution of the prevalence of obesity in the workers of a general hospital in
      Mexico.
AB  - OBJECTIVE: The objective of this study was to compare the prevalence of
      overweight and obesity in the first Prevalencia de factores de nesso
      cardiovascular en Trabajadores survey (1994) with the prevalence of overweight
      and obesity observed in the second survey (1996). RESEARCH METHODS AND
      PROCEDURES: For both surveys the following individual data were collected: age,
      sex, weight, height, and body mass index (BMI). The 1994 survey included 2383
      people and the 1996 survey included 2759 people. The degree of BMI was classified
      according to the current World Health Organization definitions. The population
      was divided by gender and age group, and the prevalence of each level of
      overweight was calculated. Additionally, the prevalence of different cutoff
      levels of BMI was calculated by gender and age groups. RESULTS: The global
      prevalence of age-adjusted overweight increased from 26.91% to 37.45%. This
      increase was observed in both genders but the men had a higher increase from
      24.51% to 40.21%. Overweight was more frequent in men than in women in all age
      groups. Male overweight prevalence was higher in the 40- to 59-year-old group and
      > or = 60-year-old group. Female overweight prevalence was predominant in the 30-
      to 39-year-old, 40- to 49-year-old, and 50- to 59-year-old groups. Global
      prevalence of obesity (> or =30 kg/m(2)) changed from 13.8% to 17.2%.
      Particularly, global prevalence of obesity class I increased from 9.66% to 12.6%;
      in men this figure increased from 9.04% to 13.05% and in women from 9.9% to
      12.71%. DISCUSSION: Prevalence of overweight and obesity has increased
      significantly in the studied population. It is necessary to implement lifestyle
      modifications to prevent the increase of prevalence of overweight and obesity.

PMID- 11331432
TI  - Central but not peripheral glucocorticoid infusion in adrenalectomized male rats
      increases basal and substrate-induced insulinemia through a parasympathetic
      pathway.
AB  - OBJECTIVE: Glucocorticoids acting through the central nervous system are
      postulated to play a role in the hyperinsulinemia and increased adiposity of
      obesity. We investigated the role of parasympathetic activation in glucocorticoid
      induced hyperinsulinemia. RESEARCH METHODS AND PROCEDURES: Plasma pancreatic
      polypeptide (PP) levels were used as an index of parasympathetic output.
      Insulinemia and plasma PP levels were measured basally and after intravenous
      glucose injection (300 mg/kg) in adrenalectomized male rats infused with
      dexamethasone (7.5 microg/kg per day) intracerebroventricularly (ICV) or
      subcutaneously (SC) for 3 to 6 days in the presence or absence of acute atropine
      blockade (1.0 mg/kg). Food intake was controlled between groups. RESULTS:
      Compared with normal rats, adrenalectomy decreased white adipose tissue depot
      weights and leptinemia, and these were restored to normal values by ICV but not
      SC dexamethasone infusion. Adrenalectomy significantly reduced insulinemia below
      normal levels, which was restored by SC dexamethasone replacement. However, ICV
      dexamethasone replacement increased insulinemia of adrenalectomized rats to
      levels higher than normal control values (basal, 500 +/- 40 pM vs. 280 +/- 40 pM;
      1-minute postglucose, 2500 +/- 180 pM vs. 1240 +/- 260 pM; p < 0.0001) and
      increased plasma PP levels, which were correlated with insulinemia. Atropine
      significantly reduced plasma insulin and PP to levels similar to normal controls
      but had no effect in any other group. DISCUSSION: These data show that
      glucocorticoids act within the brain to increase insulinemia, most likely through
      activation of parasympathetic efferent fibers. Such an affect would contribute to
      the adipogenic effects of central glucocorticoids.

PMID- 11331433
TI  - Introduction: the history of arsenic trioxide in cancer therapy.
AB  - Although arsenic can be poisonous, and chronic arsenic exposure from industrial
      or natural sources can cause serious toxicity, arsenic has been used
      therapeutically for more than 2,400 years. Thomas Fowler's potassium bicarbonate
      based solution of arsenic trioxide (As(2)O(3)) was used empirically to treat a
      variety of disorders, and in 1878, was reported to reduce white blood cell counts
      in two normal individuals and one with "leucocythemia." Salvarsan, an organic
      arsenical for treating syphilis and trypanosomiasis, was developed in 1910 by
      Paul EHRLICH: In the 1930s, arsenic was reported to be effective in chronic
      myelogenous leukemia. After a decline in the use of arsenic during the mid-20th
      century, reports from China described a high proportion of hematologic responses
      in patients with acute promyelocytic leukemia (APL) who were treated with arsenic
      trioxide. Randomized clinical trials in the U.S. led to FDA approval of arsenic
      trioxide for relapsed or refractory APL in September 2000.

PMID- 11331434
TI  - History of the development of arsenic derivatives in cancer therapy.
AB  - Arsenic is a natural substance that has been used medicinally for over 2,400
      years. In the 19th century, it was the mainstay of the materia medica. A solution
      of potassium arsenite (Fowler's solution) was used for a variety of systemic
      illnesses from the 18th until the 20th century. This multipurpose solution was
      also primary therapy for the treatment of chronic myelogenous leukemia until
      replaced by radiation and cytotoxic chemotherapy. The past 100 years have seen a
      precipitous decline in arsenic use and, by the mid-1990s, the only recognized
      indication was the treatment of trypanosomiasis. Much of this decline was due to
      concerns about the toxicity and potential carcinogenicity of chronic arsenic
      administration. The rebirth of arsenic therapy occurred in the 1970s when
      physicians in China began using arsenic trioxide as part of a treatment for acute
      promyelocytic leukemia (APL). Their accumulated experience showed that a stable
      solution of arsenic trioxide given by intravenous infusion was remarkably safe
      and effective both in patients with newly diagnosed APL leukemia and in those
      with refractory and relapsed APL. The mechanisms of action of arsenic derivatives
      in this disease and other malignancies are many and include induction of
      apoptosis, partial cytodifferentiation, inhibition of proliferation, and
      inhibition of angiogenesis. Molecular studies and ongoing clinical trials suggest
      that, as a chemotherapeutic agent, arsenic trioxide shows great promise in the
      treatment of malignant disease.

PMID- 11331435
TI  - Clinical experience of arsenic trioxide in relapsed acute promyelocytic leukemia.
AB  - Acute promyelocytic leukemia (APL) has unique clinical, cytogenetic, and
      molecular features and is one of the most potentially curable human malignancies.
      The current standard treatment given to patients with newly diagnosed APL
      consists of all-trans retinoic acid and anthracycline-based cytotoxic
      chemotherapy, which is highly effective for remission induction. However, despite
      the potential for cure with existing treatments, approximately 20%-30% of
      patients relapse and require salvage therapy. Reports of the safety and efficacy
      of arsenic trioxide from centers in China led to a pivotal trial of this agent in
      the United States for patients with relapsed APL. In an initial pilot study, 11
      of 12 patients experienced a complete response, and a subsequent multicenter
      trial confirmed the efficacy and safety of arsenic trioxide for remission
      induction in this patient population. Additional trials are under way to evaluate
      the use of this agent alone or as part of a chemotherapy regimen for
      consolidation and maintenance of patients with APL.

PMID- 11331436
TI  - Arsenic trioxide: an emerging therapy for multiple myeloma.
AB  - Arsenic trioxide can inhibit proliferation and induce apoptosis in multiple
      myeloma (MM) cells in vitro and in vivo. In addition to affecting tumor growth,
      arsenic trioxide has been shown to inhibit angiogenesis, suggesting that it may
      have significant potency in the treatment of MM. Based on these observations, the
      clinical efficacy of arsenic trioxide was evaluated in patients with advanced
      refractory MM using a fixed-dose intravenous infusion given daily for a maximum
      of 60 days. Nine patients were evaluable. All nine had extensive prior therapy;
      seven had two or more high-dose chemotherapy cycles with autologous stem cell
      support. All nine patients had cytogenetic abnormalities, and six had chromosome
      13 deletions. Of the four patients who completed more than 30 days of arsenic
      trioxide infusion, two had >50% reduction in myeloma paraprotein, one had stable
      disease, and one progressed. Of the five patients with <30 days infusion, two had
      stable disease and three progressed. Thus, on an intent-to-treat basis, two of
      nine (23%) patients responded (>50% paraprotein reduction). The regimen was well
      tolerated except for development of cytopenia, which responded to G-CSF, and a
      grade III pulmonary complication in one patient. In summary, arsenic trioxide has
      activity in end-stage, high-risk myeloma and deserves further evaluation in
      earlier-stage disease.

PMID- 11331437
TI  - Clinical trials of arsenic trioxide in hematologic and solid tumors: overview of
      the National Cancer Institute Cooperative Research and Development Studies.
AB  - Arsenic trioxide inhibits growth and promotes apoptosis in many different cancer
      cell lines. The National Cancer Institute is working cooperatively with research
      centers across the U.S. to evaluate its clinical activity in hematologic
      malignancies, such as acute promyelocytic leukemia, acute myeloid leukemia, acute
      lymphocytic leukemia, chronic myelogenous leukemia, non-Hodgkin's lymphoma,
      Hodgkin's disease, chronic lymphocytic leukemia, myelodysplastic syndrome, and
      multiple myeloma. It is also supporting research in solid tumors, such as
      advanced hormone-refractory prostate cancer and renal cell cancer and in cervical
      cancer and refractory transitional cell carcinoma of the bladder. The safety and
      pharmacokinetics of arsenic trioxide are also being evaluated in pediatric
      patients with refractory leukemia and lymphoma. The results of these ongoing
      studies should provide important insights into the clinical utility of arsenic
      trioxide in these diseases.

PMID- 11331438
TI  - Risk/benefit profile of arsenic trioxide.
AB  - Approximately 20%-30% of patients with acute promyelocytic leukemia (APL) who are
      treated with the current standard all-trans retinoic acid and anthracycline-based
      chemotherapy regimen suffer relapse. In the mid-1990s, studies from China
      reported the effective use of arsenic trioxide in achieving complete remission in
      patients with APL. In the United States, a multicenter trial of this agent in 40
      patients with relapsed APL following conventional therapy confirmed the positive
      safety and efficacy outcomes of a smaller 12-patient pilot study. Common adverse
      events were hyperleukocytosis, APL differentiation syndrome, prolonged QT
      interval on electrocardiogram, skin rash, and hyperglycemia.

PMID- 11331439
TI  - Newer antihistamines.

PMID- 11331440
TI  - Esomeprazole (nexium).

PMID- 11331441
TI  - Bivalirudin (Angiomax) for angioplasty.

PMID- 11331442
TI  - Clinical trials of the effectiveness of devices: an analogy with drugs.

PMID- 11331443
TI  - Anterior rectocele due to obstructed defecation relieved by botulinum toxin.
AB  - Background. Surgical repair of rectocele does not always alleviate symptoms
      related to difficulty in defecation, and some patients have impaired fecal
      continence after surgical treatment. To avoid complications of surgical repair,
      we investigated the efficacy of botulinum toxin in treating patients with
      symptomatic rectocele. Methods. Fourteen female patients with anterior rectocele
      were included in the study. The patients were studied by using anorectal
      manometry and defecography, and then treated with a total of 30 units of type A
      botulinum toxin, injected into 3 sites, 2 on either side of the puborectalis
      muscle and the third anteriorly in the external anal sphincter, under
      ultrasonographic guidance. Results. After 2 months, symptomatic improvement was
      noted in 9 patients (P =.0003). At the same time, rectocele depth (mean +/- SD)
      was reduced from 4.3 +/- 0.6 cm to 1.8 +/- 0.5 cm (P =.0000001) and rectocele
      area from 9.2 +/- 1.3 cm(2) to 2.8 +/- 1.6 cm(2) (P =.0000001). Anorectal
      manometry demonstrated decreased tone during straining from 70 +/- 28 mm Hg at
      baseline to 41 +/- 19 mm Hg at 1 month (P =.003) and to 41 +/- 22 mm Hg at 2
      months (P =.005). No permanent complications were observed in any patient for a
      mean follow-up period of 18 +/- 4 months. At 1 year evaluation, incomplete or
      digitally assisted rectal voiding was not reported by any patient, and a
      rectocele was not found at physical examination. Four recurrent, asymptomatic
      rectoceles were noted at defecography. Conclusions. Botulinum toxin injections
      should be considered as a simple therapeutic approach in patients with anterior
      rectocele. The treatment is safe and less expensive than surgical repair. A more
      precise method of toxin injections under transrectal ultrasonography accounts for
      the high success rate. Repeated injections may be necessary to maintain the
      clinical improvement.

PMID- 11331444
TI  - Hernioplasty and simultaneous laparoscopic cholecystectomy: a prospective
      randomized study of open tension-free versus laparoscopic inguinal hernia repair.
AB  - BACKGROUND: The laparoscopic repair of unilateral primary groin hernia remains
      controversial. This randomized study evaluates the outcome of the laparoscopic
      technique in hernia repair in patients undergoing simultaneous laparoscopic
      cholecystectomy (LC) and compares laparoscopic repair with tension-free open
      groin hernia repair. METHODS: Sixty-four low-risk patients with symptomatic
      chronic calculous cholecystitis and synchronous unilateral primary inguinal
      hernia were randomized to undergo either laparoscopic transabdominal
      preperitoneal mesh hernia repair (TAPP) and LC or LC and open tension-free hernia
      repair. RESULTS: The operating time was longer in the TAPP and LC group (mean +/-
      SD = 121 +/- 32 minutes) than in the LC and open group (95 +/- 27 minutes) (P
      <.01). The mean operating costs were higher in the TAPP and LC group ($1235
      versus $1080) (P <.03). The intensity of postoperative pain at rest was greater
      in the LC and open group at 24 hours (P <.01) and 48 hours (P <.05), with a
      greater consumption of pain medication (P <.01). No differences between the 2
      groups were found in terms of postoperative complications, disability period
      before return to work, or hernia recurrences. CONCLUSIONS: The totally
      laparoscopic procedure does not result in a significant benefit other than
      improved comfort in the first 2 postoperative days. However, laparoscopic hernia
      repair is considerably more difficult to perform than open tension-free
      hernioplasty. Thus, the totally laparoscopic approach should be performed only by
      experienced laparoscopic surgeons with special expertise in hernia surgery.

PMID- 11331445
TI  - Biological implications of tumor cells in blood and bone marrow of pancreatic
      cancer patients.
AB  - BACKGROUND: Patients with pancreatic cancer often have tumor recurrence despite
      curative resection. Cancer cells detected in blood or bone marrow at the time of
      diagnosis may relate to tumor stage and to prognosis. Recent research emphasis
      has centered on tumor cells in bone marrow aspirates, but whether these represent
      early micrometastases or blood-borne cells in transit is unknown. PATIENTS AND
      METHODS: We developed a specific immunocytochemical assay that evaluated more
      than 5.3 x 10(6) extracted mononuclear cells per sample of blood and bone marrow
      and that could identify a single tumor cell in that population. The assay was
      applied to samples of blood and bone marrow from 105 patients with pancreatic
      cancer and 66 controls. The prevalence of isolated tumor cells was compared with
      Union Internationale Contre le Cancer (UICC) stage. A multivariate Cox regression
      analysis for survival was performed. RESULTS: Pancreatic cancer cells were
      detected in 26% of blood samples and in 24% of bone marrow specimens. Specificity
      for cancer was 96%. The prevalence of isolated tumor cells in patients with
      proven resectable cancer was 9% in blood and 13% in bone marrow. The prevalence
      increased with UICC tumor stage in blood (P =.04) but not in bone marrow (P =.52)
      and correlated in blood with resectability (P =.02), progression of disease
      (P=.08), and peritoneal dissemination (P =.003). While survival correlated
      significantly with tumor stage (P <.001) and isolated tumor cells in blood
      correlated with tumor stage, the finding of cancer cells in blood or bone marrow,
      or both, was not independently associated with survival in patients with
      pancreatic cancer. CONCLUSIONS: Isolated tumor cells in blood but not bone marrow
      reflect the stage of growth and spread of pancreatic cancer, particularly in the
      peritoneal cavity. The findings are consistent with cells in bone marrow
      aspirates being in transit, not implanted. These disseminated cancer cells may be
      the consequence, rather than the cause, of progression.

PMID- 11331446
TI  - Ionic implantation of silicone chronic venous access devices does not alter
      thrombotic complications: a double-blinded, randomized clinical trial.
AB  - BACKGROUND: Ion implantation of silicone vascular catheters has been shown in
      preclinical and pilot studies to alter the thrombogenicity of silicone surfaces
      through the reduced adherence of thrombin. This prospective, randomized double
      blinded study was designed to detect differences in function related to
      thrombotic events between ion-implanted and standard silicone chronic venous
      access devices (CVAD) placed in patients with cancer who are receiving
      chemotherapy. METHODS: Patients with nonleukemic malignancies who required venous
      access for chemotherapy and who were not receiving anticoagulants were randomized
      to receive standard or ion-implanted CVAD. Postoperative functional assessments
      of the ease of infusion or aspiration were performed by oncology nurses caring
      for the patients. RESULTS: Follow-up, available for 100 of 106 randomized
      patients, showed more episodes of occlusion to aspiration in the ion implantation
      group (47%) than in the control group (39%) but this difference was not
      significant. There were no significant differences between the 2 groups in the
      number of occasions when anticoagulation or local thrombolytic therapy was
      required nor were there differences in the numbers of infection or deep venous
      thromboses. CONCLUSIONS: Ion implantation of silicone catheter material does not
      alter the incidence of local thrombotic complications of CVAD. Although there
      were no serious complications resulting from this treatment, the use of ion
      implanted catheters cannot be recommended on the basis of this trial.

PMID- 11331447
TI  - Intensity of vascular endothelial growth factor expression is associated with
      increased risk of recurrence and decreased disease-free survival in papillary
      thyroid cancer.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) induces proliferation of
      endothelial cells, stimulates angiogenesis, and increases vascular permeability.
      Increased VEGF expression has been associated with poor clinical outcomes in many
      malignancies. Several recent reports have documented over expression of VEGF in
      papillary thyroid cancer. We hypothesized that increased expression of VEGF would
      be associated with either an increased risk of recurrence or a decreased
      recurrence-free survival in papillary thyroid cancer. METHODS:
      Immunohistochemistry was used to detect VEGF expression in archival paraffin
      embedded surgical thyroid specimens from 96 subjects with papillary thyroid
      cancer. RESULTS: VEGF expression was detected in 98% (94/96) of the samples,
      predominantly of slight-to-moderate intensity in the majority of malignant cells.
      However, the specific finding of a diffuse pattern of intense immunostaining for
      VEGF was detected significantly more often than less intense, patchy
      immunostaining patterns in subjects with distant metastasis at diagnosis (63%
      versus 15%, P =.005), local recurrence (58% versus 13%, P =.001), and distant
      recurrence (83% versus 14%, P =.001). Furthermore, this specific pattern of
      diffuse, intense VEGF expression was associated with a significantly shorter
      recurrence-free survival than other staining patterns (P =.007). CONCLUSIONS:
      These data demonstrate that the immunohistochemical pattern of VEGF staining in
      the initial surgical specimen is strongly associated with the incidence of local
      and distant metastasis in papillary thyroid cancer.

PMID- 11331448
TI  - Continuous resuscitation after hemorrhage and acute fluid replacement improves
      cardiovascular responses.
AB  - BACKGROUND: Although acute fluid replacement after trauma and severe hemorrhage
      remains the cornerstone in the management of trauma victims, it remains unknown
      whether continuous resuscitation after trauma-hemorrhage and acute fluid
      replacement produces salutary effects on cardiovascular function and reduces
      proinflammatory cytokine release. METHODS: Adult male rats underwent laparotomy
      (ie, soft tissue trauma) and were bled to and maintained at a mean arterial
      pressure of 40 mm Hg until 40% of the shed blood volume was returned in the form
      of Ringer's lactate (RL). The animals were then resuscitated with 4 times the
      volume of shed blood with RL for 60 minutes, followed by continuous resuscitation
      with RL at 5 mL/h/kg for 48 hours after the acute fluid replacement. At 48 hours
      after hemorrhage, mean arterial pressure, cardiac output, and left ventricular
      contractility parameters, such as the maximal rates of ventricular pressure
      increase (+dP/dt(max)) and decrease (-dP/dt(max)), were determined. Microvascular
      blood flow in the intestine and kidney was assessed by laser Doppler flowmetry.
      In addition, plasma levels of TNF-alpha were assayed by enzyme-linked
      immunosorbent assay. RESULTS: The mean arterial pressure and cardiac output were
      decreased by 34% and 18%, respectively, at 48 hours after hemorrhage and acute
      resuscitation. Continuous resuscitation, however, markedly improved these
      parameters. Similarly, +dP/dt(max) and -dP/dt(max) decreased significantly after
      hemorrhage and acute fluid replacement but was restored to sham values after
      continuous resuscitation. Microvascular blood flow in the gut and kidneys was
      decreased after hemorrhage and acute resuscitation by 34% and 35%, respectively.
      However, intestinal and renal perfusion was maintained at the sham levels at 48
      hours after continuous resuscitation. In addition, the upregulated TNF-alpha
      after acute resuscitation alone was reduced after continuous resuscitation.
      CONCLUSIONS: Continuous resuscitation after acute fluid replacement appears to be
      a useful approach for restoring and maintaining cardiovascular function and organ
      perfusion after trauma and severe hemorrhage.

PMID- 11331449
TI  - Hypertonic saline attenuation of the neutrophil cytotoxic response is reversed
      upon restoration of normotonicity and reestablished by repeated hypertonic
      challenge.
AB  - BACKGROUND: Hypertonic saline (HTS) resuscitation, in addition to enhancing
      hemodynamic recovery, modulates postinjury hyperinflammation in the critically
      injured. The polymorphonuclear neutrophil (PMN) cytotoxic response, a key element
      in the pathogenesis of postinjury organ dysfunction, is attenuated under
      hypertonic conditions. Although plasma Na(+) rises to 180 mmol/L after HTS
      infusion, baseline levels are reestablished within 24 hours. We hypothesized that
      HTS attenuation of the PMN cytotoxic response (beta2-integrin expression,
      elastase release, and O2- production) is reversed upon return to normotonicity,
      but can be reestablished by repeated HTS challenge. METHODS: Isolated human PMNs
      were incubated in HTS (Na(+) = 180 mmol/L) for 5 minutes at 37 degrees C then
      returned to normotonicity by centrifugation and resuspension in isotonic buffer.
      Stimulated (PAF) beta2-integrin expression was measured by flow cytometry.
      Stimulated (PAF/fMLP) elastase release and O2- production were measured by
      cleavage of N-methoxysuccinyl-Ala-Ala-Pro-Val p-nitroanilide and reduction of
      cytochrome c (Cyt c). Protein tyrosine phosphorylation in PMN cell lysates was
      assessed by Western blot. RESULTS: Clinically relevant levels of HTS induced
      tyrosine phosphorylation in resting PMNs and attenuated cytotoxic responses.
      Reestablishment of normotonicity returned these functions to baseline. A repeated
      HTS challenge after restoration of normotonicity also induced tyrosine
      phosphorylation and suppressed the cytotoxic response. CONCLUSIONS: HTS
      attenuation of the PMN cytotoxic response is reversible but can be reestablished
      by repeated HTS treatment. This phenomenon may provide the unique opportunity to
      selectively and temporarily decrease the postinjury inflammatory response when
      patients are at greatest risk for PMN-mediated tissue damage.

PMID- 11331450
TI  - Growth hormone together with glutamine-containing total parenteral nutrition
      maintains muscle glutamine levels and results in a less negative nitrogen balance
      after surgical trauma.
AB  - BACKGROUND: Muscle protein catabolism, reflected by a decrease in glutamine
      (GLN), a decrease in muscle protein synthesis, and a negative nitrogen balance
      can be reduced by either administration of GLN or growth hormone (GH). In this
      study, the effects of a combination of GH and GLH were studied. METHODS: Patients
      (n = 16) undergoing abdominal operation were given total parenteral nutrition
      (TPN) containing either GLN alone or GLN together with GH (GH/GLN) during 3
      postoperative days. The amino acid concentration and protein synthesis in muscle
      tissue and the nitrogen balance were measured. RESULTS: GH/GLN reduced nitrogen
      losses compared with GLN alone (-5.8 +/- 1.4 g nitrogen versus -10.6 +/- 1.1 g
      nitrogen, P <.05). GH/GLN maintained muscle GLN at preoperative levels compared
      with a 47.5% +/- 6.3% decline in the GLN group. A similar decrease was seen in
      the fractional synthesis rate of muscle protein postoperatively in both groups.
      CONCLUSIONS: GH has an additive effect given together with GLN on muscle amino
      acid metabolism, preventing the decrease in the GLN concentration in skeletal
      muscle and diminishing the loss of whole body nitrogen. However, the improvements
      in muscle amino acid concentrations and nitrogen loss were not associated with
      differences between the groups in muscle protein synthesis postoperatively.

PMID- 11331451
TI  - Carcinoembryonic gene member 2 mRNA expression as a marker to detect circulating
      enterocytes in the blood of colorectal cancer patients.
AB  - BACKGROUND: The aim of this study was to report our experience with a new
      molecular tool to detect circulating enterocytes in the blood of patients with
      colorectal cancer. METHODS: The study included 193 individuals: 78 patients with
      colorectal cancer and 115 controls composed of patients with benign colorectal
      diseases (n = 16), patients with noncolorectal cancer (n = 31), healthy
      individuals (n = 62), and healthy bone marrow transplantation donors (n = 6). A
      nested reverse transcriptase-polymerase chain reaction with specific primers for
      the carcinoembryonic gene member 2 (CGM2) was used to detect circulating
      enterocytes in the peripheral blood of 78 patients with colorectal cancer. The
      blood (n = 109) or the bone marrow (n = 6) of the 115 controls was studied to
      test the absence of CGM2 illegitimate transcription in nucleated blood cells and
      nucleated blood cell progenitors. The assay sensitivity was effective in
      detecting 1 CGM2-positive cell per 10(6) nucleated blood cells. RESULTS: Fifty
      nine percent (46/78) of patients with colorectal cancer were found positive
      whereas all negative controls remained negative. Positivity rates were 38% (3/8)
      in Dukes' A classification, 43% (9/21) in Dukes' B, 77% (23/30) in Dukes' C, and
      58% (11/19) in Dukes' D. CONCLUSIONS: The clinical significance of enterocyte
      detection in the blood of colorectal cancer patients by means of this CGM2
      messenger RNA assay needs further evaluation.

PMID- 11331452
TI  - The combined use of prostaglandin I2 analogue (OP-2507) and thromboxane A2
      synthetase inhibitor (OKY-046) strongly inhibits atherosclerosis of aortic
      allografts in rats.
AB  - BACKGROUND: Atherosclerosis is the main lesion in allografts undergoing chronic
      rejection. We investigated the effect of OP-2507 (prostaglandin I2 analogue) and
      OKY-046 (thromboxane A2 synthetase inhibitor) on graft atherosclerosis
      morphologically and the production of eicosanoids in grafts in a rat aortic
      allograft model. METHODS: Abdominal aortic allografts of Lewis (RT-1(l)) rats
      were transplanted orthotopically into fully major histocompatibility complex
      mismatched Wistar King A/Qdj (RT-1(u)) rats that were subcutaneously administered
      OP-2507 (0.1 mg/kg/d) or OKY-046 (125 mg/kg/d), or both, with an osmotic pump.
      Four, 8, or 12 weeks later, the grafts were harvested and examined
      histologically, and the concentration of eicosanoids in the grafts were analyzed.
      RESULTS: Lewis aortic allografts in Wistar King A recipients with no treatment
      displayed atherosclerosis, which involved gradual intimal thickening and medial
      thinning with continuous inflammation in adventitia. Neither OP-2507 nor OKY-046
      treatment affected the intensity of adventitial inflammation. Although inhibition
      of medial thinning or a decrease in medial nuclear density was not observed, OKY
      046 administration alone significantly inhibited an increase in intimal
      thickness. OP-2507 administration alone significantly inhibited a decrease in
      medial nuclear density and intimal thickening. Combined treatment with OP-2507
      and OKY-046 further decreased the alteration of media and intima. The ratio of
      thromboxane B2 and 6-keto-prostaglandin F(1alpha) in the grafts was significantly
      reduced by OKY-046 but not by OP-2507 alone. CONCLUSIONS: We have demonstrated
      that atherosclerosis in aortic allografts is inhibited by the continuous
      administration of either OP-2507 or OKY-046, and a combination of both agents
      strongly increases this inhibitory effect. Amelioration of balance in eicosanoid
      production in the grafts by the use of thromboxane A2 synthetase inhibitor and
      the simultaneous usage of stable prostaglandin I2 analogue may be a strategy for
      preventing atherosclerosis that results from chronic rejection.

PMID- 11331453
TI  - Survival and functions of encapsulated porcine hepatocytes after
      allotransplantation or xenotransplantation without immunosuppression.
AB  - BACKGROUND: This study evaluated the survival and functions of encapsulated
      porcine hepatocytes after intraperitoneal allotransplantation and
      xenotransplantation without immunosuppression. METHODS: Isolated porcine
      hepatocytes were encapsulated in AN 69 polymer capsules (45.10(6)/capsule) and
      transplanted intraperitoneally in 12 rats and 12 pigs. Fifteen, 30, and 60 days
      after transplantation, capsules were removed and the viability and morphology of
      explanted hepatocytes were examined under light and electronic microscopy. The
      potential to produce albumin was assessed by evaluating the level of albumin
      messenger RNA, using semiquantitative reverse transcription-polymerase chain
      reaction. 6beta-Hydroxylase activity was measured by high-performance liquid
      chromatography. In addition, cytochrome P450 3A proteins were detected by Western
      blot only in allogeneic hepatocytes. RESULTS: Similar results were observed after
      allotransplantation and xenotransplantation. Histologic studies showed that
      hepatocytes were well-preserved and arranged in cords for up to 30 days. The
      expression of porcine albumin gene was maintained up to 15 days. 6beta
      Hydroxylase activity was 2.5-fold lower at day 15 than in freshly encapsulated
      hepatocytes, which were not transplanted. In allogeneic hepatocytes, the
      expression of CYP 3A protein was detected up to 60 days after transplantation.
      CONCLUSIONS: Encapsulated porcine hepatocytes remain viable and functional for at
      least 15 days after allotransplantation and xenotransplantation without
      immunosuppression. The demonstration of maintained hepatic functions in
      transplanted porcine hepatocytes up to 15 days is a first step toward application
      in the treatment of acute liver failure.

PMID- 11331454
TI  - Malnutrition-induced macrophage apoptosis.
AB  - BACKGROUND: Human and murine studies suggest protein-calorie malnutrition (PCM)
      results in significant host immunosuppression resulting in increased morbidity
      and mortality. Apoptosis has been implicated as an important mediator in the
      immunosuppression observed in several disease states. This study was designed to
      characterize macrophage apoptosis in a murine model of PCM and investigate
      components that regulate the apoptotic process, such as protein kinase C (PKC)
      and Bcl-2 activity. METHODS: Swiss-Webster mice (n = 50) were randomly assigned
      to receive either a control (24% protein) or a PCM diet (0% protein) for 7 days.
      Peritoneal macrophages were harvested and detection of apoptosis was performed by
      terminal deoxy-transferase-mediated deoxyuridine triphosphate (dUTP) nick-end
      labeling (TUNEL) and propidium iodide DNA staining under baseline and pro
      apoptotic conditions. Pro-apoptotic conditions included cells treated with tumor
      necrosis factor-alpha (TNF-alpha) (10 ng/mL), interferon-gamma (IFN-gamma) (10
      ng/mL), and a combination of both agents. In addition, levels of PKC activity and
      expression of Bcl-2 and p53 protein were measured. RESULTS: Peritoneal
      macrophages from PCM mice had a significantly greater amount of apoptosis at
      baseline and under stimulated conditions compared with controls. Levels of PCM
      apoptosis were elevated at baseline by TUNEL staining compared with macrophages
      from the control group (16.5% +/- 1.4%, versus 4.5% +/- 1.1%, P <.01). In
      addition, peritoneal macrophages from the malnourished animals were significantly
      more susceptible to the apoptotic effect of TNF-alpha and the effects of INF
      gamma (27.3% +/- 2.1% and 31% +/- 1.4%) compared with control mice (5.5% +/- 0.7%
      and 7.2% +/- 0.5%, P <.01), respectively. Again, an increase in the baseline
      apoptosis rate was demonstrated in peritoneal macrophages from PCM mice compared
      with control fed mice (13.2% +/- 4.4% versus 4.3% +/- 3.1%, P <.01) as measured
      by propidium iodide staining. The combination of agents, TNF-alpha and INF-gamma,
      resulted in an additive apoptotic effect in the malnourished host compared with
      the control animals (43.4% +/- 4.7% versus 10.5% +/- 2.2%, P <.01), respectively.
      Furthermore, there was a significant decrease in the mean total PKC activity in
      the malnourished macrophages compared with results in controls (110,000 +/- 8000
      versus 60,000 +/- 4000 cpm, P <.01). Similar changes were also observed in PKC
      cytosolic and membrane activity between both groups. In addition, Bcl-2 protein
      expression was significantly decreased in PCM animals compared with control
      animals. CONCLUSIONS: Thus, peritoneal macrophages from PCM mice exhibit
      significantly greater levels of apoptosis at baseline and when stimulated with
      pro-apoptotic agents compared with controls. The propensity of macrophages from
      PCM mice to undergo apoptosis may be attributable in part to decreased PKC
      activity and Bcl-2 protein expression. These findings may help to explain the
      associated immune dysfunction observed in malnutrition.

PMID- 11331455
TI  - Overproduction of transforming growth factor-beta1 (TGF-beta1) is associated with
      adhesion formation and peritoneal fibrinolytic impairment.
AB  - BACKGROUND: Reduction in peritoneal fibrinolytic capacity and increased
      transforming growth factor-beta1 (TGF-beta1) production are associated with
      adhesion development. This study investigated the expression of TGF-beta1 in
      peritoneal tissue, and possible correlation with components of the fibrinolytic
      system locally in peritoneal tissue. MATERIALS AND METHODS: Peritoneal samples
      were taken from 22 patients at relaparotomy. Samples of adhesions were collected
      from 10 patients. The patients were categorized into different groups depending
      on the quantity and the quality of adhesions. TGF-beta1 and components of the
      fibrinolytic system in tissue extracts were assayed using enzyme-linked
      immunosorbent assays. RESULTS: The concentration of active TGF-beta1 in
      peritoneal samples from patients with extensive adhesions was double (P <.01)
      that of healthy subjects, but the total levels of TGF-beta1 were similar (P
      =.63). In adhesion tissue, both active (P <.003) and total (P <.008) TGF-beta1
      concentrations were more than twice as high as unaffected peritoneum. There was a
      significant correlation between the concentration of plasminogen activator
      inhibitor type 1 in peritoneal samples with active TGF-beta1 (P <.03, r = 0.693)
      and adhesion tissue with total TGF-beta1 (P =.001, r = 0.872). The other
      components of the fibrinolytic system did not correlate significantly with TGF
      beta1. CONCLUSIONS: These data indicate that an overexpression of TGF-beta1 is
      associated with adhesion formation, possibly through a mechanism involving local
      regulation of plasminogen activator inhibitor type 1.

PMID- 11331457
TI  - Down and out in Pittsburgh.

PMID- 11331456
TI  - Evidence against a role for polymorphisms at tumor necrosis factor, interleukin-1
      and interleukin-1 receptor antagonist gene loci in the regulation of disease
      severity in acute pancreatitis.
AB  - BACKGROUND: Cytokines such as tumor necrosis factor-alpha (TNF-alpha) and
      interleukin-1beta (IL-1beta) and their endogenous antagonists such as IL-1
      receptor antagonist (IL-1RA) are important mediators of disease severity in acute
      pancreatitis. Because the level of secretion of these cytokines is determined in
      part by genetic factors, the aim of this study was to examine the influence of
      genetically determined cytokine secretion upon disease severity in acute
      pancreatitis. METHODS: TNF (TNF-308, TNFB), IL-1beta, and IL-1 receptor
      antagonist (IL-1RA) genotypes were determined for 190 patients with acute
      pancreatitis and 102 healthy volunteers. To further assess the influence of
      genetic factors, the cytokine phenotype for TNF-alpha, IL-1beta, and IL-1RA was
      determined by using a whole blood culture technique in 51 patients after
      recovery. RESULTS: The distributions of TNF-308, TNFB, IL-1beta, and IL-1RA gene
      polymorphisms were similar in patients with mild or severe acute pancreatitis.
      Further, no difference in gene polymorphism frequencies was observed between
      patients with acute pancreatitis and healthy controls. With respect to phenotype,
      the secretion of TNF-alpha was similar in patients with previous mild and severe
      acute pancreatitis; however, the IL-1beta: IL-1RA ratio was significantly lower
      in patients with previous severe acute pancreatitis than in those with mild
      disease. CONCLUSIONS: Our observations suggest that genetic factors are not
      important in determining TNF-alpha secretion in patients with acute pancreatitis.
      However, a predetermined imbalance between IL-1beta and its antagonist IL-1RA
      would appear to exist in patients with severe acute pancreatitis, although the
      genetic basis for this altered relationship could not be determined.

PMID- 11331458
TI  - Perforated Meckel's diverticulum.

PMID- 11331459
TI  - Genetic susceptibility to hemorrhagic complications during warfarin therapy.

PMID- 11331460
TI  - An adult-to-adult living donor liver transplant using dual left lobe grafts.

PMID- 11331461
TI  - On the prognosis criteria for hepatic resection in cases of breast metastasis.

PMID- 11331463
TI  - Control of hemorrhage during laparoscopic splenectomy.

PMID- 11331464
TI  - [Ultrastructure and molecular biochemistry on pathogenic fungal cells: the
      architecture of septal cell walls of dermatophytes].
AB  - This review provides abstracts of our research for which the year 2000 prize of
      The Japanese Society for Medical Mycology was awarded. The study consists of 4
      fields: 1)Ultrastructure and biochemistry of the cell walls of dermatophytes. 2)
      Freeze-fracture electron microscopic study on the membrane systems of pathogenic
      fungi. 3) Action mechanisms of antifungal agents in terms of membrane structure
      and functions. 4) Dimorphism and virulence of pathogenic fungi in terms of
      molecular biology of membrane lipids. Since the detailed contents of these
      studies were reported in my previous review article (Jpn J Med Mycol 41: 211-217,
      2000), I would like to mention these studies only briefly here, together with a
      detailed review of the septal cell wall architecture of dermatophytes, which I
      did not cover in my earlier articles.

PMID- 11331465
TI  - Species identification system for dermatophytes based on the DNA sequences of
      nuclear ribosomal internal transcribed spacer 1.
AB  - This describes a new and reliable species identification and classification
      system for dermatophytes based on the cluster analysis of nuclear ribosomal
      internal transcribed spacer 1 (ITS1) DNA sequences. In this system, some
      phenotypically similar species construct a compact monophyleic cluster which
      seems to be a species. This ITS1 sequence based species is called an ITS1
      genospecies. The classification of genospecies is a practical concept for DNA
      sequence based species identification. It is possible to perform species
      identification and/or strain typing of 25 major dermatophytes (anamorphic genera
      Trichophyton, Microsporum, Epidermophyton, and the teleomorphic genus
      Arthroderma), some of which are hard to identify from their morphological
      features, by demonstrating their dendrogram using this system.

PMID- 11331466
TI  - Molecular analyses of the serotype of Cryptococcus neoformans.
AB  - Cryptococcus neoformans consists of two varieties and is divided into five
      serotypes: serotypes A, D and AD (C. neoformans var. neoformans) and serotypes B
      and C (C. neoformans var. gattii). This article deals with the investigation on
      the serotype of C. neoformans by molecular analysis technique in place of the
      immunological method with antisera against the capsule component of the yeast.
      For easier and more precise epidemiological surveillance, twenty-seven isolates
      of C. neoformans were molecularly analyzed by a RAPD method. This method
      differentiated these isolates of C. neoformans into 4 groups corresponding to the
      serotypes A, D, AD and complex of serotypes B and C. These results indicated that
      serotype A, D and AD could be differentiated by the molecular analysis technique
      described here. Furthermore, nucleotide sequences of CAP59 genes from five
      serotypes of C. neoformans were analyzed for their phylogenetic relationship.
      Approximately 600-bp genomic DNA fragments of the CAP59 gene were amplified from
      each isolate by PCR and sequenced. The CAP59 nucleotide sequences of C.
      neoformans showed more than 90% similarity among the five serotypes. The
      phylogenetic analysis of their sequences was divided into three clusters:
      serotype A and AD, serotype B and C, and serotype D. These results also indicated
      that serotype B and C isolates belonging to var. gattii were genetically
      homogeneous and closely related.

PMID- 11331467
TI  - US-Japan workshops in medical mycology: past, present and future.
AB  - The Extramural Mycology Program of the National Institutes of Health (NIH),
      National Institute of Allergy and Infectious Diseases (NIAID) has organized and
      implemented a five workshop series in medical mycology during a critical period
      in the evolution of contemporary medical mycology (1992 to 2000;
      http://www.niaid.nih.gov/research/dmid.htm). The goals of the workshop series
      were to: initiate interactions; build collaborations; identify research needs;
      turn needs into opportunities; stimulate molecular research in medical mycology;
      and summarize recommendations emerging from the workshop proceedings. A recurring
      recommendation in the series was to foster communications within and beyond the
      field of medical mycology. US-Japan interactions were noted as one specific
      example of potential information exchange for mutual benefit. The first formal
      action directed at this recommendation was the workshop Emergence and Recognition
      of Fungal Diseases convened under the auspices of the US-Japan Cooperative
      Medical Science Program (USJCMSP; http://www.niaid.
      nih.gov/dmid/us%5Fjapan/default.htm) in Bethesda, Maryland USA on 30 June 1999
      (D.M. Dixon & T. Matsumoto, co-chairs). A major goal of the workshop was to
      present contemporary medical mycology to the Joint Committee of the USJCMSP
      through representative research presentations in order to make the Committee
      aware of current status in the field, and the potential for scientific
      interactions. The second formal action is the workshop, under the auspices of the
      Japanese Society for Medical Mycology Medical Perspectives of Fungal Genome
      Studies scheduled for 28 November 2000 in Tokyo, Japan (T. Matsumoto & D.M.
      Dixon, co-chairs). The NIAID Mycology Workshop series recommended interactions
      between the following groups: academic and pharmaceutical; medical and molecular
      (model systems); medical and plant pathogens; basic and clinical; mycologists and
      immunologists. The first two US-Japan workshops can be viewed as consistent with
      these recommendations, and serve as a Western/Eastern gateway for exchange. The
      focus of the second US-Japan workshop on genome projects for the medically
      important fungi provides an excellent model for international communications.
      Given the tsunami of information that is flowing from genomics and
      bioinformatics, it is clear that global interactions will be essential in
      managing and interpreting the data.

PMID- 11331469
TI  - [A case of Folliculitis barbae Candidomycetica].
AB  - A 71-year-old man was referred to our department on January 30, 1998 with hard
      red papules that had developed on the philtrum in mid-January. On January 2, the
      patient had received high-dose steroid therapy (pulse therapy) for cluster asthma
      attacks and antibiotics at the Department of Internal Medicine of our hospital.
      Infiltrative, protruding reddish plaques were observed on the philtrum, which
      contained a number of small pustules at sites corresponding to hair follicles.
      There was partial opacity and slight irregularity of the nail plates on the first
      and second toes of the right foot. Fungal elements were detected from a lesion on
      the mustache and the nail. Histological examination of the lesion on the philtrum
      revealed infiltration of inflammatory cells comprising neutrophils, lymphocytes,
      and macrophages around the hair follicles. Beard hair and nail cultures revealed
      Candida albicans A, indicating that the patient had candidal sycosis and candidal
      onychia. He was treated with oral fluconazole (100 mg/day). The lesion was
      clinically improved within 50-days. Recently, extensive use of steroids and
      antibiotics has produced an increase in reports of patients with Folliculitis
      barbae Candidomycetica. We believe that the present case was also induced by high
      dose steroid therapy and antibiotics.

PMID- 11331468
TI  - [Advances in molecular biology of dermatophytes].
AB  - During the 44th meeting of The Japanese Society for Medical Mycology in Nagasaki,
      2000, a forum was held entitled Advances in Molecular Biology of Dermatophytes.
      Based on the subject, target molecules and kind of approach, we selected seven
      presentations from over 100 of the poster abstracts. Six of them concerned
      identification and one concerned viability. Summaries of the 7 presentations are
      given in this article. Of presentations on the identification methods, 5
      demonstrated their usefulness: 1) A sequence analysis of ITS 1 region in
      ribosomal DNA of several Microsporum species showed ITS 1 genospecies Arthroderma
      otae to be composed of A. otae, M. canis, M. equinum and M. audouinii. 2) RAPD
      may be useful for identifying isolates which are not clearly identifiable by
      conventional biological techniques. 3) Sequence analysis of CHS 1 was shown to be
      a rapid tool for species level identification of M. gypseum. 4) PCR-SSCP analysis
      was also useful for discrimination of dermatophytes with high reproducibility and
      sensitivity. 5) Strain identification of A. benhamiae isolates may be possible
      using RFLP analysis of NTS regions in ribosomal DNA. The other presentation
      concerning identification pointed out some important problems: RFLP of
      mitochondrial DNA and ITS sequencing of A. benhamiae showed that the results are
      sometimes in conflict with those obtained from biological techniques, or in some
      cases, between other molecular techniques. This implies that our concept of
      fungal species needs to be re-examined and perhaps amended. The presentation on
      viability introduced quantitative analysis of mRNA of ACT gene, a new application
      of a molecular technique. Since the mRNA expresses only in living cells, the
      method is highly useful as an indicator of fungal viability.

PMID- 11331470
TI  - Molecular identification of a clinical isolate of non-pigmented and asporogenic
      Aspergillus fumigatus strain which cannot be identified by traditional
      morphological methods.
AB  - A non-pigmented and asporogenic fungal strain without taxonomically useful
      characteristics was isolated from sputum of a patient with chronic bronchitis.
      Although the taxonomic position could not be determined based on traditional
      morphological criteria, the fungus was identified as an Aspergillus fumigatus
      mutant strain by molecular techniques including ITS sequence analysis and PCR
      identification system using a PCR primer pair specific for A. fumigatus.
      Usefulness of these molecular techniques for the identification of non
      classifiable fungal strains in a clinical laboratory is discussed.

PMID- 11331471
TI  - Identification of Candida dubliniensis based on the specific amplification of
      mitochondrial cytochrome b gene.
AB  - Candida dubliniensis, a recently described Candida species, is frequently
      isolated from oral candidiasis in human immunodeficiency virus infected
      individuals. To detect the organism rapidly, we have developed specific
      oligonucleotide primers based on the sequences of mitochondrial cytochrome b
      gene. These primers selectively amplified DNA only from C. dubliniensis; the DNAs
      of all pathogenic Candida species tested, as well as those of medically relevant
      yeasts such as Cryptococcus neoformans, and Trichosporon cutaneum, were not
      amplified. This is the first report describing the effectiveness of cytochrome b
      gene in PCR based detection of an organism, and we hope the system will be useful
      as a microbiological tool for rapid detection of C. dubliniensis.

PMID- 11331472
TI  - Early treatment with antibiotics reduces the need for surgery in acute
      necrotizing pancreatitis--a single-center randomized study.
AB  - Pancreatic infection is the main indication for surgery and the principal
      determinant of prognosis in acute necrotizing pancreatitis. Previous studies on
      the effects of antibiotics have not, however, uniformly demonstrated any
      reduction in the need for surgery or any decrease in mortality among these
      patients, although the incidence of pancreatic infections was significantly
      reduced. This single-center randomized study was designed to compare early vs.
      delayed imipenem treatment for acute necrotizing pancreatitis. Ninety patients
      with acute necrotizing pancreatitis (C-reactive protein > 150 mg/L, necrosis on
      CT) were randomized within 48 hours either to a group receiving imipenem (1.0 g
      plus cilastatin intravenously 3 times a day) or a control group. Not included
      were those who had been started on antibiotics at the referring clinic, those who
      were taken directly to the intensive care unit for multiorgan failure, and those
      who refused antibiotics or might have had adverse reactions. Thirty-two patients
      were excluded because they were over 70 years of age (not potentionally operable)
      or for any study violation. There were 25 patients in the imipenem group and 33
      patients in the control group. The main end point was the indication for
      necrosectomy due to infection (i.e., after the initial increase and decrease,
      there was a second continuous increase in temperature, white blood cell count [>
      30%] and C-reactive protein [> 30%], with other infections ruled out, or bacteria
      were found on Gram stain of the pancreatic fine-needle aspirate). In the control
      group, imipenem was started when the operative indication was fulfilled.
      Conservative treatment was continued for at least 5 days before necrosectomy. The
      study groups did not differ from each other with regard to sex distribution,
      patient age, etiology, C-reactive protein concentration, and extent of pancreatic
      necrosis on CT. Two (8%) of 25 patients in the imipenem group compared to 14
      (42%) of 33 in the control group fulfilled the operative indications (P = 0.003).
      Nine patients in the control group responded to delayed antibiotics but five had
      to undergo surgery. Of those receiving antibiotics, 2 (8%) of 25 in the early
      antibiotic (imipenem) group needed surgery compared to 5 (36%) of 14 in the
      delayed antibiotic (control) group (P = 0.04). Two (8%) of 25 patients in the
      imipenem group and 5 (15%) of 13 patients in the control group died (P = NS [no
      significant difference]). Seven (28%) of 25 in the imipenem group and 25 (76%) of
      33 in the control group had major organ complications (P = 0.0003). Based on the
      preceding criteria, early imipenem-cilastatin therapy appears to significantly
      reduce the need for surgery and the overall number of major organ complications
      in acute necrotizing pancreatitis, and reduces by half the mortality rate; this
      is not, however, statistically significant in a series of this size.

PMID- 11331473
TI  - Effect of preoperative chemoradiotherapy on surgical margin status of resected
      adenocarcinoma of the head of the pancreas.
AB  - We examined the effect of preoperative chemoradiotherapy on the ability to obtain
      pathologically negative resection margins in patients undergoing
      pancreaticoduodenectomy for adenocarcinoma of the head of the pancreas. Between
      1987 and 2000, 100 patients underwent Whipple resection with curative intent for
      primary adenocarcinoma of the head of the pancreas. Pathologic assessment of six
      margins (proximal and distal superior mesenteric artery, proximal and distal
      superior mesenteric vein, pancreas, retroperitoneum, common bile duct, and
      hepatic artery) was undertaken by either frozen section (pancreas and common
      duct) or permanent section. A margin was considered positive if tumor was present
      less than 1 mm from the inked specimen. Margins noted to be positive on frozen
      section were resected whenever possible. Of the 100 patients treated, 47 (47%)
      underwent postoperative radiation and chemotherapy (group I) and 53 (53%)
      received preoperative chemoradiotherapy (group II) with either 5-fluorouracil (32
      patients) or gemcitabine (21 patients). Patient demographics and operative
      parameters were similar in the two groups, with the exception of preoperative
      tumor size (CT scan), which was greater in group II (P < 0.001), and number of
      previous operations, which was greater in group II (P < 0.0001). Statistical
      analysis of the number of negative surgical margins clear of tumor was performed
      using Fisher's exact test. All patients (100%) had six margins assessed for
      microscopic involvement with tumor. In the preoperative therapy group, 5 (7.5%)
      of 53 patients had more than one positive margin, whereas 21 (44.7%) of 47
      patients without preoperative therapy had more than one margin with disease
      extension (P < 0.001). Additionally, only 11 (25.6%) of the 47 patients without
      preoperative therapy had six negative margins vs. 27 (50.9%) of 53 in the group
      receiving preoperative therapy (P = 0.013). Survival analysis reveals a
      significant increase in survival in margin-negative patients (P = 0.02).
      Similarly, a strong trend toward improved disease-free and overall survival is
      seen in patients with a single positive margin vs. multiple margins. Overall, we
      find a negative impact on survival with an increasing number of positive margins
      (P = 0.025, hazard ratio 1.3). When stratified for individual margin status,
      survival was decreased in patients with positive superior mesenteric artery (P =
      0.06) and vein (P = 0.04) margins. However, this has not yet resulted in a
      significant increase in disease-free or overall survival for patients receiving
      preoperative therapy (P = 0.07).

PMID- 11331474
TI  - Angiogenesis inhibitor TNP-470 reduces human pancreatic cancer growth.
AB  - In this study we investigated the effects of the angiogenesis inhibitor TNP-470
      on human pancreatic cancer cells in vitro and in vivo. The action of TNP-470 on
      vascular endothelial growth factor (VEGF) was also assessed. In vitro human
      pancreatic cancer cells (MIAPaCa-2, AsPC-1, and Capan-1), and human umbilical
      vein endothelial cells (HUVEC) were exposed to increasing concentrations (1 pg/ml
      to 100 microg/ml) of TNP-470. Cell proliferation was assessed after 3 days by
      cell count and MTT assay. In vivo, 5 x 10(6) pancreatic cancer cells were
      injected subcutaneously into nude mice. Four weeks later, 1 mm3 fragments of the
      resulting tumors were implanted into the pancreas of other mice. Animals received
      either TNP-470 (30 mg/kg every other day) or vehicle subcutaneously for 14 weeks.
      The volume of the primary tumor and metastatic spread were determined at autopsy.
      Concentrations of VEGF were determined in serum (VEGF(S)) and ascites (VEGF(A))
      by enzyme-linked immunosorbent assay. Microvessel density was analyzed by
      immunohistochemistry in CD31-stained tumor sections. In vitro, proliferation and
      viability of the human pancreatic cancer cell lines were significantly inhibited
      at high concentrations of TNP-470 (> 1 microg/ml). In contrast, TNP-470
      effectively decreased the growth of HUVEC at 100 pg/ml. In vivo, tumor volume and
      dissemination scores were significantly lower in all three pancreatic cancer cell
      lines. VEGF(S) and VEGF(A) were not different between treated groups. Treatment
      with TNP-470 significantly reduced neoangiogenesis in tumors of all three human
      pancreatic cancer cell lines: MIAPaCa-2 = 74.8 +/- 7.8/0.74 mm2 vs. 24.8 +/-
      3.7/0.74 mm2; AsPC-1 = 65.3 +/- 5.0/0.74 mm2 vs. 26.0 +/- 3.4/0.74 mm2; and Capan
      1 = 82.2 +/- 5.8/0.74 mm2 vs. 26.9 +/- 2.5/0.74 mm2 (P < 0.001). However,
      survival was not statistically different between groups. TNP-470 reduced tumor
      growth and metastatic spread of pancreatic cancer in vivo. This was probably due
      to the antiproliferative effect of the agent on endothelial cells rather than to
      the direct inhibition of pancreatic cancer cell growth. TNP-470 activity was not
      associated with alteration of VEGF secretion.

PMID- 11331475
TI  - Therapy for pancreatic cancer with a recombinant humanized anti-HER2 antibody
      (herceptin).
AB  - The HER2/neu oncogene is overexpressed in human pancreatic cancer, but the
      clinical significance of that overexpression is uncertain. In the present study
      we investigated the antitumor efficacy of Herceptin, a new recombinant humanized
      anti-HER2/neu antibody, which exhibits cytostatic activity on breast and prostate
      cancer cells that overexpress the HER2 oncogene. That antibody may retard tumor
      growth in certain patients with those diseases. We quantified HER2 expression in
      various human pancreatic cancer cell lines and studied the bioactivity of this
      antibody both in vitro and in vivo. Growth inhibition by Herceptin was observed
      in vitro in cell lines with high levels of HER2/neu expression. Cell lines with
      low levels of this protein did not respond significantly to the antibody. In vivo
      we studied two different pancreatic cancer cell lines in an orthotopic mouse
      model of the disease. Herceptin treatment suppressed tumor growth in the MIA PaCa
      2 tumor cell line, which expressed high levels of HER2/neu. These data suggest
      that Herceptin treatment of patients with pancreatic cancer who express high
      levels of the HER2/neu oncogene may be reasonable.

PMID- 11331476
TI  - Synthetic peptide YY analog binds to a cell membrane receptor and delivers
      fluorescent dye to pancreatic cancer cells.
AB  - Pancreatic cancer continues to have a dismal prognosis despite multimodality
      treatment plans. Peptide YY (PYY) is a gut hormone that suppresses pancreatic
      exocrine and endocrine function. Previous experiments have shown that shortened
      synthetic PYY(22-36) analog decreases pancreatic cancer cell growth while also
      decreasing intracellular cyclic adenosine monophosphate. Our purpose was to
      construct an optimal synthetic PYY analog that binds to pancreatic cancer cells
      that may be used for imaging and therapy. Biotinylated PYY analogs with lengths
      ranging from PYY(1-36), PYY(9-36), PYY(14-36), PYY(22-36), and PYY(27-36) were
      tested with flow cytometry and receptor cross-linking studies to measure cell
      membrane binding. Growth inhibition studies were also performed using
      monotetrazolium tests to determine potency of various PYY analogs. Quantitative
      flow cytometry reveals the highest specific binding of PYY(14-36) to pancreatic
      cancer cells. Cross-linking studies reveal a receptor on the cell membrane of
      human pancreatic ductal adenocarcinoma cells. Growth inhibition studies reveal
      that PYY (14-36) has the highest potency against PANC-1 and MiaPaCa-2 cells. A
      novel synthetic PYY analog binds to the cell surface of pancreatic cancer cells
      and has the ability to deliver fluorescent dyes. The strategy of using
      biotinylated peptides to deliver avidin-dye complexes to cancer cells will allow
      imaging of pancreatic tumors and delivery of therapeutic agents.

PMID- 11331477
TI  - Long-term prospective assessment of functional results after proctectomy with
      coloanal anastomosis.
AB  - The objective of this study was to prospectively assess the long-term functional
      results after restorative proctectomy with coloanal anastomosis for rectal
      cancer. Thirty consecutive patients (18 males; mean age 59.6 +/- 9.8 years, range
      40 to 75 years) underwent proctectomy with coloanal anastomosis for rectal cancer
      between January 1990 and March 1997. Cancers were located between 5 and 12 cm
      from the anal verge. Differences existed in the administration of adjuvant
      therapy and in the kind of anastomotic reconstruction. An 8 cm colonic J-pouch
      was fashioned in 11 patients. The coloanal anastomosis was protected by a
      diverting loop ileostomy in 22 patients. All patients were evaluated using a
      prospective patient-completed protocol to record daily bowel activity over a 1
      week period at 3, 6, and 12 months, and yearly thereafter. Mean follow-up extends
      to 55.5 +/- 27 months (range 7 to 117 months). There were no perioperative
      deaths. Four patients (13.3%) developed a clinically evident anastomotic
      dehiscence. Overall, stool frequency decreased from 4.4 +/- 2.5 bowel movements
      per day at 3 months to 3.0 +/- 2.8 bowel movements per day at 5 years. Patients
      with a J-pouch had a lower stool frequency in comparison to patients with an end
      to-end coloanal anastomosis during the entire study period (from 3.2 +/- 2.2 vs.
      3.9 +/- 2.7 bowel movements per day at 6 months to 2.8 +/- 1.9 vs. 3.4 +/- 4.0
      bowel movements per day at 5 years; no statistical significance). The percentage
      of continent patients increased from 50% at 6 months to 75% at 5 years; the
      percentage of patients with incontinence for solid stool and with frequent
      incontinence (&dollar;7 episodes per week) decreased from 35.7% at 6 months to
      12.5% at 5 years. The influence of the type of anastomosis, dehiscence,
      protective stoma, J-pouch, radiation therapy, and gender was evaluated with
      univariate analysis. Although there was no statistically significant correlation
      between any of these variables and the development of incontinence, when
      incontinence occurred, a history of anastomotic dehiscence increased the number
      of episodes of incontinence per week and the percentage of episodes of
      incontinence for solid stools at 6 months, 2 years, and 5 years (P < 0.05 and P <
      0.001, respectively); the use of preoperative radiation therapy increased the
      number of episodes of incontinence per week at 6 months, 1 year, 2 years, and 5
      years (P < 0.01) and the percentage of episodes of incontinence for solid stools
      at 3 and 6 months and 1 and 2 years (P < 0.04); and the presence of a J-pouch
      increased the number of episodes of incontinence per week at 1 and 2 years (P <
      0.03 and 0.005, respectively) and the percentage of episodes of incontinence for
      solid stools at 2, 3, and 4 years (P < 0.05). These data suggest that the
      functional results after proctectomy with coloanal anastomosis improve at least
      over the course of the first 5 postoperative years. Furthermore, when
      incontinence develops, its severity is made worse by the occurrence of an
      anastomotic dehiscence, the use of preoperative radiation therapy, and the
      presence of a J-pouch.

PMID- 11331478
TI  - Fibrin glue for all anal fistulas.
AB  - The aim of this study was to determine if a new sphincter muscle-sparing
      technique that uses fibrin glue was effective in closing all types of anal
      fistulas. All patients with anal fistulas who were seen by a single surgeon over
      a 2-year period were treated with fibrin glue. Six to 8 weeks after a seton was
      placed in the fistula tract, either autologous fibrin glue or commercially
      available fibrin sealant was used to close the fistula tract. Twenty patients
      were treated with a mean follow-up of 10 months. Etiology of the anal fistulas
      was as follows: cryptoglandular in 13, Crohn's disease in four, and miscellaneous
      in three. Fibrin glue closure of the anal fistula was successful initially in 15
      patients (75%) and was successful after a second treatment in two additional
      patients, for an overall fibrin glue fistula closure rate of 85% (17 of 20).
      Functional results have remained excellent with no patient reporting any change
      in continence after treatment. Fibrin glue is simple and effective treatment for
      all anal fistulas with excellent functional results.

PMID- 11331479
TI  - Contribution of intraoperative enteroscopy in the management of obscure
      gastrointestinal bleeding.
AB  - Obscure gastrointestinal bleeding remains a significant diagnostic challenge. Our
      aims were (1) to determine the efficacy of intraoperative enteroscopy (IOE) in
      identifying lesions responsible for obscure gastrointestinal bleeding and (2) to
      determine the outcome of patients after treatment of these lesions. We
      retrospectively reviewed all patients who underwent IOE for obscure
      gastrointestinal bleeding from 1992 to 1998. Patients were divided into those
      with overt and those with occult gastrointestinal bleeding. Follow-up was
      complete in 67 patients (96%), with a median of 32 months (range 1 to 91 months).
      Seventy patients (52 overt and 18 occult) underwent IOE after extensive
      preoperative evaluation. Median duration of bleeding was 12 months, requiring a
      median of 14 blood transfusions. Risk factors for bleeding were identified in 46
      patients (61%). A lesion was identified and treated in 52 patients (74%)-39 in
      the overt group and 13 in the occult group. Lesions identified were vascular
      (54%), ulcerations (31%), tumors (11%), and small bowel diverticula (4%).
      Overall, 35 patients (52%) were found to have one or more lesions at IOE that
      were treated surgically and had no further bleeding. IOE, through a mid-small
      bowel enterotomy, has low morbidity and is effective in that it identified a
      treatable lesion in 74% of patients, which led to cure of bleeding in 52%.

PMID- 11331480
TI  - Segmental living related small bowel transplantation in adults.
AB  - The advent of small bowel transplantation has provided selected patients with
      chronic intestinal irreversible failure with a physiologic alternative to total
      parenteral nutrition. Recently a standardized technique for living related small
      bowel transplantation (LR-SBTx) has been developed. Three patients with short
      bowel syndrome underwent LR-SBTx at our institution. All donors were ABO
      compatible with a good human leukocyte antigen match. A segment of 180 to 200 cm
      of ileum was harvested and transplanted with its vascular pedicle constituted by
      the ileocolic artery and vein. The grafts were transplanted with a short cold and
      warm ischemia time. The immunosuppression regimen consisted of oral FK-506,
      prednisone, and intravenous induction with atgam. Serial biopsies of the
      intestinal grafts were performed to evaluate rejection or viral infections. The
      postoperative course was uneventful for all donors. All of the recipients are
      currently alive and well. Two of three patients are off total parenteral
      nutrition and tolerating an oral diet with no limitations on daily activity. In
      the third patient, the graft was removed 6 weeks after transplantation. At the
      time of enterectomy, no technical or immunologic complications were documented.
      Absorption tests for D-xylose and fecal fat studies were performed showing
      functional adaptation of the segmental graft. All biopsies were negative for
      acute rejection. A well-matched segmental ileal graft from a living donor can
      provide complete rehabilitation for patients with short bowel syndrome. Our
      initial experience suggests that the risk of acute rejection and infection is
      greatly reduced compared to cadaveric bowel transplantation. Further clinical
      application of this procedure is warranted.

PMID- 11331481
TI  - Upregulation of ornithine decarboxylase mRNA expression in Barrett's esophagus
      and Barrett's-associated adenocarcinoma.
AB  - The Barrett's multistage process is characterized histopathologically by
      progression from Barrett's intestinal metaplasia to Barrett's esophagus with
      dysplasia and ultimately adenocarcinoma. Understanding the cellular and molecular
      events in this multistage process may contribute to improved diagnosis and
      treatment. Ornithine decarboxylase (ODC) is the first enzyme in the biosynthesis
      of polyamines. Elevated ODC activity has been found to be associated with
      progression during Barrett's esophagus, but the regulation of ODC gene expression
      in the development of Barrett's-associated adenocarcinoma has not been reported.
      The aim of this study was to assess the prevalence and timing of ODC mRNA
      expression in the Barrett's metaplasia-dysplasia-adenocarcinoma sequence. ODC
      mRNA expression levels, relative to the stably expressed internal reference gene
      beta-actin, were measured using a quantitative reverse transcription-polymerase
      chain reaction (RT-PCR) method (ABI 7700 Sequence Detector System) in 104
      specimens from 19 patients with Barrett's esophagus without carcinoma and 22
      patients with Barrett's-associated adenocarcinoma. The median ODC mRNA expression
      levels were significantly increased in Barrett's esophagus tissues compared to
      matched normal tissues in patients without adenocarcinoma of the esophagus (P =
      0.002; Wilcoxon test). A significant progressive increase in ODC mRNA expression
      was detectable through the stages of the metaplasia-dysplasia-carcinoma sequence
      in patients with Barrett's-associated adenocarcinoma (r = 0.719; P < or = 0.001;
      Spearman's rho test). These findings show that upregulation of ODC mRNA
      expression is an early event in the development and progression of Barrett's
      associated adenocarcinoma of the esophagus, and they suggest that high ODC mRNA
      expression levels may be a clinically useful biomarker for the detection of
      occult adenocarcinoma

PMID- 11331482
TI  - Pharyngeal pH monitoring in 222 patients with suspected laryngeal reflux.
AB  - To determine the existence of and characterize gastroesophagopharyngeal reflux in
      patients with symptoms of airway irritation, we monitored pharyngeal pH over a 24
      hour period in 222 consecutive patients. Pharyngeal reflux was defined as a drop
      in pH to less than 4 at the pharyngeal sensor, which occurred simultaneously with
      acidification of the distal esophagus. Patients were divided into two groups:
      those with pharyngeal reflux (PR+) and those without (PR-). The Mann-Whitney U
      test and Student's t test were used to assess intergroup comparisons. Episodes of
      pharyngeal reflux (range 1 to 36, average 4.4) were identified in 90 PR+ patients
      (40%). No pharyngeal reflux was identified in the remaining 132 patients (PR-).
      Episodes of pharyngeal reflux were rapidly cleared (average duration 1.5
      minutes), and occurred while in the upright position in 77 (86%) of 90 patients
      and while in the supine position in 11 (12%) of 90 patients. Twenty-three
      patients (25%) experienced symptoms in association with an episode of pharyngeal
      reflux. In the distal esophagus, the percentage of time the pH was below 4 during
      the upright position and the total percentage of time the pH was below 4 were
      greater in PR+ patients (6.4% and 5.8%, respectively) when compared to PR-
      patients (2.6% and 2.6%, respectively). Laryngoscopic findings did not
      distinguish PR+ from PR- patients. Pharyngeal reflux occurs most commonly in the
      upright position and can be identified in more than 40% of patients thought to
      have acid-induced laryngeal symptoms. Even though these episodes are short lived
      and rapidly cleared, symptoms occur concomitantly in 25% of patients with proven
      pharyngeal reflux. Patients with laryngeal symptoms and documented pharyngeal
      reflux have greater amounts of esophageal reflux when compared to patients with
      laryngeal symptoms and no demonstrable pharyngeal reflux.

PMID- 11331483
TI  - A decision analysis of the optimal initial approach to achalasia: laparoscopic
      Heller myotomy with partial fundoplication, thoracoscopic Heller myotomy,
      pneumatic dilatation, or botulinum toxin injection.
AB  - In the absence of randomized controlled trials that directly compare all of the
      modern methods of managing achalasia, decision analysis may help determine the
      optimal treatment strategy. Four strategies for the initial management of
      achalasia were compared using the following decision model: (1) laparoscopic
      Heller myotomy and partial fundoplication; (2) pneumatic dilatation; (3)
      botulinum toxin injection; and (4) thoracoscopic Heller myotomy. Probabilities of
      clinical events and utilities of health states were estimated using review of the
      medical literature and patient interviews. A recursive decision tree (Markov
      model) was used to simulate all the important outcomes of each initial treatment
      option, allowing for complications, relapses over time, and transitions between
      strategies when appropriate. After 10 years, laparoscopic Heller myotomy with
      partial fundoplication was associated with the longest quality-adjusted survival
      (quality-adjusted life years [QALY] = 7.41). The difference between this strategy
      and either pneumatic dilatation or botulinum toxin injection was small.
      Thoracoscopic Heller myotomy was associated with the poorest quality-adjusted
      survival (QALY = 7.15). Pneumatic dilatation was the favored strategy when the
      effectiveness of laparoscopic surgery at relieving dysphagia was less than 89.7%,
      the operative mortality risk was greater than 0.7%, or the probability of reflux
      after pneumatic dilatation was less than 19%. In a decision model, laparoscopic
      Heller myotomy with partial fundoplication is at least as effective as endoscopic
      approaches for managing achalasia symptoms. However, the differences are small
      enough that patient preferences and local expertise should be taken into
      consideration when tailoring a treatment plan for an individual patient.

PMID- 11331485
TI  - Problem-based learning. A critical review of its educational objectives and the
      rationale for its use.
AB  - Over the past 30 years there has been an increasing interest in curriculum
      innovation in medical schools in North America, the United Kingdom, Netherlands,
      and Australia. Since the introduction of problem-based learning at McMaster
      University in Canada in 1969, several medical schools throughout the world have
      adopted problem-based learning as the educational and philosophical basis of
      their curricula. Several studies have shown that problem-based learning is an
      important educational strategy for integrating the curriculum, motivating the
      students and helping them to identify their learning issues and set their own
      learning goals. However, there is a great deal of concern regarding what problem
      based learning means and the advantages of problem-based learning over
      traditional curriculum have not been clearly addressed. In this review, a broad
      range of the definitions of problem-based learning have been addressed and the
      rationale for problem-based learning and its educational objectives are
      discussed.

PMID- 11331484
TI  - Rationale for the combination of cryoablation with surgical resection of hepatic
      tumors.
AB  - Only 5% to 10% of metastatic and primary liver tumors are amenable to surgical
      resection. Hepatic cryoablation has increased the number of patients who are
      suitable for curative treatment. The aim of this study was to evaluate survival
      and intrahepatic recurrence in patients treated with cryoablation and resection.
      From June 1994 to July 1999, thirty-eight surgically unresectable patients
      underwent a total of 42 cryoablative procedures for 65 malignant hepatic lesions.
      Twenty patients underwent cryoablation alone, and 18 patients were treated with a
      combination of resection and cryoablation, with a minimum of 18 months' follow
      up. The 38 patients had the following malignancies: primary hepatocellular
      carcinoma (n = 8) and metastases from colorectal cancer (n = 21), neuroendocrine
      tumors (n = 3), ovarian cancer (n = 3), leiomyosarcoma (n = 1), testicular cancer
      (n = 1), and endometrial cancer (n = 1). Patients were evaluated preoperatively
      with spiral CT scans and intraoperatively with ultrasound examinations for lesion
      location and cryoprobe guidance. Local recurrence was detected by CT. Major
      complications included bleeding in three patients and acute renal failure,
      transient liver insufficiency, and postoperative pneumonia in one patient each.
      Two patients (5%) died during the early postoperative interval; mean hospital
      stay was 7.1 days. Median follow-up was 28 months (range 18 to 51 months).
      Overall survival according to Kaplan-Meier analysis was 82%, 65%, and 54% at 12,
      24, and 48 months, respectively. Forty-eight-month survival was not significantly
      different between those patients undergoing cryoablation alone (64%) and those
      treated with a combination of resection and cryoablation (42%). Disease-free
      survival at 45 months was 36% for patients undergoing cryoablation plus resection
      compared to 25% for those undergoing cryoablation alone. Local recurrences were
      detected at five cryosurgical sites, for a rate of 12% overall (5 of 42), 11% (2
      of 18) for patients in the cryoablation plus resection group, and 12% (3 of 24)
      for those in the cryoablation alone group. For patients with colorectal
      metastases, survival was 70% at 30 months compared to 33% for hepatocellular
      cancer and 66% for other types of tumors. Patients with tumors larger than 5 cm
      or numbering more than three did not have significantly decreased survival.
      Cryoablation of hepatic tumors is a safe and effective treatment for some
      patients not amenable to resection. The combination of cryoablation and resection
      results in survival comparable to that achieved with cryoablation alone.

PMID- 11331486
TI  - Current evaluation and management of renal and ureteral stones.
AB  - A systematic clinical approach is required for the diagnosis and management of
      renal and ureteral stones. The presenting symptoms, past medical history,
      medications, and physical examination all provide clues to the diagnosis of
      urinary stones. In the acute setting, noncontrast helical computerized tomography
      has emerged as the first line imaging test for renal colic. More traditional
      imaging tests are also important in the management of stone disease. After making
      the diagnosis of a urinary stone, the urologist should discuss the advantages and
      disadvantages of all treatment options with the patient. For most stone patients
      today, many equally effective treatment approaches can exist for the same
      problem. To help direct surgical management, guidelines for stone management have
      been devised. With technologic advances, stone treatment has improved and
      complications have decreased. While patient care has been significantly impacted
      by use of effective endourologic techniques, patients should complete imaging
      tests following surgery to assure a stone-free state. In addition, recurrent
      stone formers should complete a medical stone evaluation to identify treatable
      causes of their stones.

PMID- 11331487
TI  - Physician-Nurse communication. Perceptions of Physicians in Riyadh.
AB  - OBJECTIVE: The need for communication between nurse and physician in clinical
      practice is undisputed. The objectives of this study were to describe doctors'
      perceptions of their communication with nurses, as related to the openness of the
      communication and the accuracy of the information communicated and to examine if
      specific sociodemographic characteristics concerning physicians were associated
      with perception of communication. METHODS: The sample consisted of 200 physicians
      selected randomly from 6 randomly selected hospitals representing both general
      and private. A modified Shortell's Intensive Care Unit physician-nurse
      communication subscale was used to measure the physician's perceptions of the
      degree to which openness and accuracy described their communication with nurses.
      Data was collected via a self-administered pilot questionnaire, which also
      included sociodemographic characteristics. RESULTS: The overall mean score for
      openness was 2.61 and 3.19 for accuracy out of a maximum score of 5. For openness
      the highest mean score was obtained for "listening to physician (4.31)" and the
      lowest mean score was obtained for "hospital environment (1.84)". For accuracy,
      the highest mean score was obtained for "use of medical language (4.37)" and the
      lowest mean score was for "feedback (1.84)". The results showed a significant
      difference for experience, age and gender for both types of hospitals. For
      specialization, title and nationality no significant difference was observed for
      both types of hospitals for openness and accuracy. Multivariate regression
      analysis showed that gender, age and experience were the predictor variables for
      openness and accuracy. With more experienced, older aged females, having the
      highest mean score. CONCLUSION: Communication between physician and nurses needs
      not remain only a researchable issue; its viability and vitality are crucial to
      the changing health care scene. Thus, the development of health delivery models
      that will enable effective multidisciplinary communication, cooperation and wiser
      use of limited resources in health care is essential.

PMID- 11331488
TI  - Echocardiographic dimensions and maximal oxygen uptake in elite soccer players.
AB  - OBJECTIVE: To assess cardiac dimensions in elite Saudi soccer players, and to
      correlate these measurements with maximal oxygen uptake. METHODS: Twenty-three
      soccer players representing the Saudi National soccer team, and 19 untrained
      males participated in this study. Cardiac dimensions were measured by M-mode
      echocardiography, and maximal oxygen uptake was assessed by open-circuit
      spirometry during treadmill running. RESULTS: When compared with age-matched
      untrained males, soccer players appeared to have significantly (P < 0.05) greater
      values (mm.m-2) in left ventricular end-diastolic dimension (28.8 +/- 2.7 vs 26.5
      +/- 2.3), right ventricular cavity (14.1 +/- 2.5 vs 11.8 +/- 2.6), left atrial
      cavity (16.7 +/- 1.6 vs 14.9 +/- 2.2) and left ventricular mass (117.4 +/- 21.2
      vs 89.0 +/- 16.0 g.m-2). There was no significant difference between the 2 groups
      in left ventricular posterior wall (5.3 +/- 0.77 vs 5.3 +/- 0.61) or in
      interventricular septum (5.5 +/- 0.65 vs 5.2 +/- 0.59). When soccer players were
      grouped by playing position, there were no significant differences in cardiac
      dimensions between the players, though the midfielders and the full-backs showed
      the highest values for left ventricular cavity and maximal oxygen uptake.
      Further, maximal oxygen uptake relative to body mass (ml.kg.(-1) min(-1))
      exhibited a significant correlation with left ventricular cavity normalized to
      either body mass (r = 0.62; P <0.01), or to body surface area (r = 0.53; P <
      0.05). CONCLUSION: The elite Saudi soccer players appear to have significantly
      greater left ventricular cavity and mass than age-matched untrained males. Such
      cardiac adaptation seems to result from the highly dynamic nature of the soccer
      game.

PMID- 11331490
TI  - Toxoplasmosis in a group of glucose-6-phosphate dehydrogenase deficient patients.
AB  - OBJECTIVE: This was a retrospective study that aimed at evaluating the relative
      risk of Toxoplasma infection in patients with glucose-6-phosphate dehydrogenase
      deficiency as compared to a control group with no glucose-6-phosphate
      dehydrogenase deficiency. METHODS: Ninety-one blood donor volunteers had serology
      testing from Toxoplasma gondii and were screened for glucose-6-phosphate
      dehydrogenase deficiency by a qualitative method using fluorescent spot test.
      They were all males and their ages ranged from 17 to 52 years. RESULTS: Fifty
      three persons (58%) were glucose-6-phosphate dehydrogenase deficient and 38 (42%)
      were glucose-6-phosphate dehydrogenase normal. In the glucose-6-phosphate
      dehydrogenase deficient group, 31 (58.5%) had positive titers for Toxoplasma;
      while in the glucose-6-phosphate dehydrogenase normal group 9 persons (24%) had
      positive titers for Toxoplasma. The relative risk of infection was 2.5 times more
      in the glucose-6-phosphate dehydrogenase deficient group, a statistically
      significant difference with a p value of 0.002. CONCLUSION: Glucose-6-phosphate
      dehydrogenase deficiency seems to increase the risk for Toxoplasma infection by
      2.5 fold probably due to decreased killing effect, of phagocytic cells.

PMID- 11331489
TI  - Urinary tract infection. Diabetics and non-diabetic patients.
AB  - OBJECTIVE: To determine the clinical characteristics, risk factors, causative
      organisms and antimicrobial susceptibility in diabetics and non-diabetics
      admitted to King Abdulaziz University Hospital Medical Unit to decide on the use
      of empiric antimicrobial therapy. METHODS: Significant bacteriuria from the
      Medical Unit of King Abdulaziz University Hospital from January 1999 to August
      1999 were included in the study. Medical records were reviewed and the patients
      were divided into 2 groups according to the presence or absence of diabetes. The
      following information was recorded, patients' age, sex, type of infection
      (community or hospital acquired), presence of dysuria, urinary catheter,
      intensive care unit admission, duration of hospital stay, type of organism
      isolated and their antimicrobial susceptibility. RESULTS: A total of 182
      specimens were studied, 58 (32%) were diabetics. Mean age of diabetics was 64
      years versus 54 years in non-diabetics and the male:female ratio was 1:1.6 versus
      1:1.1 (p0.001, 0.03). Urinary catheters were present in 12/58 (20%) diabetics and
      31/124 (25%) non-diabetics, intensive care unit admission was in 23/58 (40%)
      versus 38/124 (31%), and duration of hospital stay was 43 days versus 38 days
      (p0.6, 0.1, 0.4). Escherichia coli was isolated in 9/50 (18%) hospital acquired
      infections and 4/8 (50%) community acquired infections in diabetics versus 26/106
      (25%) and 8/18 (47%) in non diabetics. Pseudomonas species were isolated in 16/50
      (32%) and 1/8 (13%) in diabetics and 22/106 (21%) and 0/18 in non-diabetics.
      Escherichia coli and pseudomonas in both groups showed resistance to ampicillin
      and sensitivity to aminoglycoside and ciprofloxacin. CONCLUSION: Diabetics were
      older with high female ratio compared to non-diabetics. Escherichia coli is the
      most common isolate in community and hospital acquired infections in non
      diabetics, while Escherichia coli was common in community acquired infection and
      pseudomonas was the predominant isolate in hospital acquired infection in
      diabetics. Aminoglycoside and ciprofloxacin can be used empirically to treat both
      types of infection in diabetics and non-diabetics.

PMID- 11331491
TI  - Clinical features of systemic sclerosis.
AB  - OBJECTIVE: This descriptive study was carried out to determine the clinical and
      epidemiological pattern of systemic sclerosis in Iraqi patients who prove to have
      the disease. METHODS: Between March 1997 and December 1999, 75 patients, 67
      females and 8 males, were studied at 2 teaching hospitals in Baghdad, Iraq. The
      diagnosis of the disease was based on clinical findings, biochemical,
      serological, and pulmonary function tests. RESULTS: All the patients had
      Raynaud's phenomenon, 72 (96%) had arthralgia, 65 (87%) had dysphagia, 62 (83%)
      had atrophic changes or hypo/hyperpigmentation, 43 (58%) had telangiectasia, and
      3 (4%) had subcutaneous calcification. Of the patients studied, 2 patients (3%)
      had hypertension, one had severe hypertension. Twenty-three patients (31%) had
      anemia, 58 (77%) had elevated erythrocyte sedimentation rate and 7 patients (9%)
      with renal impairment. Rheumatoid factor was positive in 17 patients (23%) and
      antinuclear antibody in 50 (67%). Abnormal chest x-ray was reported in 50
      patients (67%). Pulmonary function tests showed restrictive pattern in 53 (71%)
      patients and obstructive pattern in 3 (4%). Electrocardiogram changes were seen
      in 3 (4%) of the patients. Three juvenile cases were reported, and familial
      tendency was noted in one patient. The results were compared with other studies
      and there were interesting differences and similarities. CONCLUSION: Systemic
      sclerosis is a rare disease in Iraq, nevertheless sporadic cases at a peak age of
      20-40 years were reported. Generally the clinical picture was comparable to other
      studies, however Raynaud's phenomenon is more prevalent in our patients and
      antinuclear antibody is less common.

PMID- 11331492
TI  - Factors affecting fertility following radical versus conservative surgical
      treatment for tubal pregnancy.
AB  - OBJECTIVE: The aim of this study was to analyze the fertility prognosis after
      conservative or radical surgery for ectopic pregnancy. Also, to identify any
      biological factors that may influence the fertility outcome after an ectopic
      pregnancy. METHODS: A retrospective study which was carried out by collating
      information from the patient's hospital records was performed on 137 cases of
      confirmed ectopic pregnancy between January 1990 and December 1995 at the
      Security Forces Hospital Riyadh, Kingdom of Saudi Arabia. The outcome measure of
      term pregnancy rate and repeat ectopic pregnancy rate was analyzed up to 3 years
      after the diagnosis of index ectopic pregnancy. RESULTS: Our results showed that
      the term pregnancy rates were not significantly different following radical or
      conservative surgical treatments for ectopic pregnancy, P > 0.05, (50% in the
      conservative group compared with 56% in the radical group). But equally
      important, the risk of a further ectopic was not increased in the radical surgery
      group, P >0.05 (11% in the conservative group as compared to 8% in the radical
      group). The incidence of intrauterine pregnancy rate (term pregnancy +
      miscarriage) was also comparable in each group. Multivariate regression analysis
      showed that the factors associated with higher fertility were age 30 years or
      less, past history of term pregnancy and a negative history of infertility (P <
      0.05). CONCLUSION: No significant difference in intrauterine pregnancy rates or
      repeat ectopic pregnancy rates were found after radical or conservative surgical
      treatment for tubal pregnancy. The patient's age, previous obstetric performance
      and a history of infertility significantly influenced fertility following the
      index ectopic pregnancy.

PMID- 11331493
TI  - Obstetrical outcomes amongst preterm singleton births.
AB  - OBJECTIVE: The purpose of this study was to review the outcome of preterm
      singleton neonatal morality based on birthweight and gestational age at delivery.
      METHODS: A retrospective review of hospital case notes of maternity data and
      neonatal mortality data was carried out on all singleton preterm deliveries from
      26 to < 37 completed weeks between 1996 and 1999 to investigate neonatal death.
      RESULTS: There were 20,758 live-born singleton deliveries over the study period,
      of which 638 were preterm (3%). The overall neonatal mortality in the preterm
      group was 42/1000. The neonatal mortality rate fell with advancing gestational
      age from 174/1000 live births at 28 weeks to 37/1000 live births at < 37
      completed weeks of gestation. The neonatal mortality rate also fell with
      increasing birth-weight from 285/1000 live births of 1000g to 14/1000 live births
      at 2500g. There was a significant increase in the proportion of babies delivered
      spontaneously. CONCLUSION: This study has demonstrated neonatal mortality using
      gestational age and birth weight. The results will be of use in obstetric
      management when elective preterm delivery is considered, and for providing
      prognostic guidance following preterm delivery.

PMID- 11331494
TI  - Relationship between breast-feeding duration and acute respiratory infections in
      infants.
AB  - OBJECTIVE: To study the relationship of breast-feeding duration on the frequency
      of respiratory tract infections in infants during the first 2 years of life.
      METHODS: A retrospective study where the files of infants randomly selected from
      Shamasan Primary Health Care Center were analyzed for different related factors
      and frequencies of respiratory infections. RESULTS: The mean duration of
      lactation was shorter than in previous national reports (5.1 +/- 3.4 months). The
      frequencies of respiratory infections were high in the first 2 years reaching an
      average of 9.2 +/- 4.1 attacks per infant. The lower respiratory tract suffered
      more frequent attacks than the upper averaging a rate of 5.6 +/- 2.6 attacks per
      infant compared to 3.7 +/- 2.2 attacks per infant. The multiple regression models
      pointed out to highly significant predictors for respiratory infection rates:
      Lactation duration (p < 0.001) for the 2 years rates, child rank (p < 0.001) for
      the first year rates and family income (p < 0.001) for the 2nd year rates.
      CONCLUSION: The lactation duration has an important relation to the frequency of
      respiratory infections in infancy. Every effort should be made to encourage and
      support longer duration of breast-feeding.

PMID- 11331495
TI  - Continuous double loop closure for midline laparotomy wounds.
AB  - OBJECTIVE: To determine the efficiency of continuous double loop closure of
      midline laparotomy wounds and how it prevents and reduces wound dehiscence.
      METHODS: A prospective study of one hundred patients who underwent laparotomy
      through midline incision in Basrah General Hospital over a one year period. This
      study is designed to compare the difference between 2 suturing techniques for
      closure of midline laparotomy wounds, one is new and unpopular to use, which is
      the continuous double loop closure, and the other one is the continuous mass
      closure technique. RESULTS: By comparison of the 2 techniques, we found that
      infection of wounds was less using the continuous double loop closure technique
      (12%) as compared with the control (18%). We also found that wound dehiscence is
      nil with the continuous double loop closure technique as compared to 8% with the
      control. CONCLUSION: The continuous double loop closure technique is superior in
      closure of midline laparotomy wounds and prevention of wound dehiscence and we
      recommend it for closure of these wounds in high risk patients.

PMID- 11331496
TI  - Random total antiepileptic drug levels and seizure control during pregnancy.
AB  - OBJECTIVE: To study the correlation of randomly-tested total antiepileptic plasma
      levels and seizure control in a retrospectively collected group of pregnant
      epileptic Saudi women. METHODS: The medical records of 30 Saudi epileptic female
      patients were reviewed during their subsequent pregnancies (total of 50). The
      type of antiepileptic drugs used during each pregnancy, the dose of each drug and
      the corresponding total plasma levels were noted. Antiepileptic drugs assay were
      carried out randomly during pregnancy either by TDX or a sensitive high
      performance liquid chromatography method. RESULTS: A total of 50 pregnancies were
      studied. The most common seizure type in these women was complex partial seizure
      followed by primary generalized epilepsy, myoclonic seizures and of least
      occurrence was the simple partial seizure with secondary generalization. All
      patients were received antiepileptic drugs, including either carbamazepine,
      phenytoin, valporic acid, phenobarbitone or clonazepam. In a total of 24
      pregnancies (48%), the serum levels of antiepileptic drugs were subtherapeutic
      during the first trimester. Recurrent seizures occurred in a total of 20
      pregnancies (40%) especially in the 3rd trimester. CONCLUSION: It is concluded
      that subtherapeutic serum levels of antiepileptic drugs correlated highly with
      the increased frequency of seizure in these pregnant women. Monitoring of state
      of seizure control in epileptic pregnant women should be made regularly during
      the course of their pregnancies.

PMID- 11331498
TI  - Endobronchial inflammatory pseudotumor of the lung.
AB  - Inflammatory pseudotumor (also called plasma cell granuloma, histiocytoma and x
      anthofibroma) is a benign, slow growing lesion which may present with cough,
      dyspnea, hemoptysis and unresolving pneumonia or can be discovered
      radiographically as a localised lesion. It has been reported in individuals up to
      70 years old, but approximately two-thirds have developed in individuals under 30
      years of age. The sex incidence is approximately equal. Inflammatory pseudotumors
      of the lung are usually peripheral lesions but may occasionally be endobronchial.
      We report the case of an endobronchial inflammatory pseudotumor in a 17-year-old
      girl who presented with unresolving right-sided pneumonia. Appropriate
      radiological, bronchoscopic and histopathological investigations lead to accurate
      pre-operative diagnosis and early complete surgical resection through a limited
      right main bronchus incision (bronchotomy). The patient made good postoperative
      recovery and an excellent prognosis is anticipated.

PMID- 11331497
TI  - In vitro effect of different non-steroidal anti-inflammatory drugs on human
      polymorphonuclear leukocyte activity measured by luminol-dependent
      chemiluminescence of the whole blood.
AB  - OBJECTIVE: To define the well-known variability in the effects of non-steroidal
      anti-inflammatory drugs and to search for predictors of such variability using an
      in vitro model. METHODS: Polymorphonuclear leukocyte activity was measured by
      luminol-dependent chemiluminescence of the whole blood using barium sulphate as a
      stimulator. Blood was taken from 40 apparently healthy volunteers (22 males and
      18 females; their age ranged from 20-50 years). Drugs (indomethacin 10 ug/ml,
      aspirin 300 ug/ml, ibuprofen 25 ug/ml or diclofenac 8 ug/ml) were added into the
      blood of each individual in vitro. The chemiluminescence was measured in a photon
      counting system. RESULTS: There was a marked inter and intra individual variation
      in the chemiluminescence response to the 4 non-steroidal anti-inflammatory drugs,
      added in vitro. The variation exhibited a continuous pattern. No statistically
      significant correlation was found between the in vitro effect of one non
      steroidal anti-inflammatory drug and the other 3 drugs, nor between the effect of
      each drug and factors like age, sex, weight, height, packed cell volume,
      hemoglobin percentage and white blood cell count. Subjects with hemoglobin-AS
      type (number = 9) responded mainly by enhancement to indomethacin and diclofenac.
      When the number of subjects rather than the average net effect was compared
      according to blood groups, those with blood group A showed chemiluminescence
      responses towards enhancement with indomethacin and diclofenac and blood group O
      with aspirin. A consistent pattern of enhancement and inhibition was evident;
      enhancements and inhibitions by any 2 drugs involve a seemingly constant
      proportion of subjects. CONCLUSION: Luminol-dependent chemiluminescence responses
      of polymorphonuclear leukocyte activity could be a good in vitro model to study
      the variability in response to non-steroidal anti-inflammatory drugs.
      Characteristics of each individual are not able to predict the pattern of
      variability. Abnormal hemoglobin and the type of blood group seem to be an
      interesting area for research.

PMID- 11331499
TI  - Gigantic jejunal leiomyosarcoma.
AB  - Jejunal leiomyosarcoma is a rare neoplasm. We report a case of gigantic
      leiomyosarcoma of the jejunum in a 30-year old man who presented with abdominal
      distension, pain and constipation. Computerized tomography scan revealed a giant
      tumor filling the entire abdominal cavity. Fine needle aspiration cytology was
      suspicious. At laparotomy, a huge jejunal leiomyosarcoma measuring 30 x 25 x 19
      cm and weighing 13 kg was completely excised. To the best of our knowledge, this
      is the first case of a giant jejunal leiomyosarcoma.

PMID- 11331500
TI  - Cold cellulitis: an unusual presentation of leprosy.

PMID- 11331501
TI  - Medical students viva: random versus structured format.

PMID- 11331502
TI  - Epidemiology of stroke in Saudi Arabia.

PMID- 11331503
TI  - Reproductive energetics and thermoregulatory status of nestlings in pampas mice
      Akodon azarae (rodentia: sigmodontinae).
AB  - We evaluated metabolic rates during reproduction and the thermoregulatory status
      of preweaning pups of Akodon azarae (Fisher 1829). Metabolic rates during late
      pregnancy and lactation were 159% and 200%, respectively, of the basal metabolic
      rate. Metabolic rates of 10-d-old pups were 447% of the adult's metabolic rates.
      No difference in metabolic rates of pups was detected among different ambient
      temperatures. Differences were detected in body temperatures between pups without
      mothers before and after exposure to different ambient temperatures below the
      thermoneutral zone. Differences were not detected in body temperatures among
      solitary or grouped pups.

PMID- 11331504
TI  - When nonshivering thermogenesis equals maximum metabolic rate: thermal
      acclimation and phenotypic plasticity of fossorial Spalacopus cyanus (Rodentia).
AB  - Many small mammals inhabiting fluctuating and cold environments display enhanced
      capacity for seasonal changes in nonshivering thermogenesis (NST) and
      thermoregulatory maximum metabolic rate (MMR). However, it is not known how this
      plasticity remains in a mammal that rarely experiences extreme thermal
      fluctuations. In order to answer this question, we determined body mass (m(b)),
      basal metabolic rate (BMR), NST, MMR, and minimum thermal conductance (C) on a
      Chilean fossorial caviomorph (Spalacopus cyanus) from a coastal population,
      acclimated to cold (15 degrees C) and warm (30 degrees C) conditions. NST was
      measured as the maximum response of metabolic rate (NST(max)) after injection of
      norepinephrine (NE) in thermoneutrality minus BMR. Maximum metabolic rate was
      assessed in animals exposed to enhanced heat-loss atmosphere (He-O2) connected
      with an open-flow respirometer. Body mass and metabolic variables increased
      significantly after cold acclimation with respect to warm acclimation but to a
      low extent (BMR, 26%; NST, 10%; and MMR, 12%). However, aerobic scope (MMR/BMR),
      calculated shivering thermogenesis (ST), and C did not change with acclimation
      regime. Our data suggest that physiological plasticity of S. cyanus is relatively
      low, which is in accordance with a fossorial mode of life. Although little is
      known about MMR and NST in fossorial mammals, S. cyanus has remarkably high NST;
      low MMR; and surprisingly, a nil capacity of ST when compared with other rodents.

PMID- 11331505
TI  - Use of serum biochemistry to evaluate nutritional status and health of incubating
      common eiders (Somateria mollissima) in Finland.
AB  - During 1997-1999, we collected serum samples from 156 common eider (Somateria
      mollissima) females incubating eggs in the Finnish archipelago of the Baltic Sea.
      We used serum chemistry profiles to evaluate metabolic changes in eiders during
      incubation and to compare the health and nutritional status of birds nesting at a
      breeding area where the eider population has declined by over 50% during the past
      decade, with birds nesting at two areas with stable populations. Several changes
      in serum chemistries were observed during incubation, including (1) decreases in
      serum glucose, total protein, albumin, beta-globulin, and gamma-globulin
      concentrations and (2) increases in serum uric acid, creatine kinase, and beta
      hydroxybutyrate concentrations. However, these changes were not consistent
      throughout the 3-yr period, suggesting differences among years in the rate of
      carbohydrate, lipid, and protein utilization during incubation. The mean serum
      concentrations of free fatty acids, glycerol, and albumin were lowest and the
      serum alpha- and gamma-globulin levels were highest in the area where the eider
      population has declined, suggesting a role for nutrition and diseases in the
      population dynamics of Baltic eiders.

PMID- 11331506
TI  - Individual variation in field metabolic rate of kittiwakes (Rissa tridactyla)
      during the chick-rearing period.
AB  - Field metabolic rate (FMR), using the doubly labelled water (DLW) method, was
      measured in free-ranging adult kittiwakes (Rissa tridactyla) early and late in
      the chick-rearing period at Svalbard, Norway. Individual variation in FMR was
      analysed by comparing FMR with body mass, sex, nest attendance, chick age, brood
      size, and basal metabolic rate (BMR). Mean FMR of kittiwakes during the chick
      rearing period was 27.0+/-0.9 (SE) W kg(-1), while the individual variation
      (calculated as coefficient of variation [CV]) in FMR was 24%. Sex, time spent
      away from the nest, age of the chicks, and brood size contributed significantly
      to FMR and explained 65% of the variation in FMR. The FMR increased by 32% from
      early until late in the chick-rearing period. This occurred simultaneously with
      an increase in the time spent away from the nest. In 15 of 20 pairs, one of the
      mates had 15% or higher (mean of the 15 pairs, 22%+/-8%) FMR (W kg(-1)) than
      their partner, even though the mates spent equal amounts of time away from the
      nest. This indicates an intrapair conflict in FMR. The variation in total FMR of
      pairs was 40% less than the individual variation, and total FMR of pairs
      increased with age of the chicks. This indicates that the mates adjust their
      energy expenditure within a relatively constant FMR determined by the energy
      needs of the chicks. Individual variation in FMR could not be explained by
      variation in body mass or BMR. BMR measured late in the chick-rearing period was
      26% lower than previous measurements of BMR from the prebreeding and incubation
      periods. The increase in FMR and simultaneous decrease in BMR caused a 40%
      increase in metabolic intensity (FMR/BMR) of kittiwakes during the chick-rearing
      period. It is suggested that the metabolic intensity is not a proper measure of
      the metabolic load in seabirds.

PMID- 11331507
TI  - Follicular development and plasma yolk precursor dynamics through the laying
      cycle in the European starling (Sturnus vulgaris).
AB  - We investigated the quantitative matching of plasma yolk precursor supply (the
      plasma pool) to follicle demand during yolk formation in European starlings
      (Sturnus vulgaris). Plasma concentrations of the two yolk precursors,
      vitellogenin (VTG) and very low density lipoprotein (VLDL), were only elevated
      coincident with rapid yolk development (RYD) and matched variation in total yolky
      follicle mass. VTG and VLDL were low (<0.4 microg/mL and <4.2 mg/mL,
      respectively) in nonbreeders and prebreeders with no yolky follicles, and at
      clutch completion. They increased to 4.02 microg/mL and 19.4 mg/mL in birds with
      a full follicle hierarchy (F1-F4), and concentrations then remained high and
      actually increased up to the point where only a single, yolky (F1) follicle
      remained. However, there was some evidence for mismatching of supply and demand:
      (a) precursor concentrations increased throughout the laying cycle even though
      the number of developing follicles decreased. We suggest that this is because of
      a requirement to maintain a large precursor pool to maintain high uptake rates;
      and (b) in birds with a full follicle hierarchy, precursor concentrations were
      negatively correlated with total follicle mass. This suggests that high uptake
      rates in large follicles can actually deplete circulating precursor
      concentrations. Plasma concentrations of both yolk precursors increased rapidly
      in the early morning with (predicted) time after ovulation, consistent with a
      lack of fine control of precursor concentrations. However, mean plasma VTG
      concentrations did not differ between morning or evening samples. In contrast,
      plasma VLDL concentrations were lower in the morning (16.8 mg/mL) than in the
      evening (22.9 mg/mL). Although there is marked individual variation in plasma VTG
      and VLDL (four- to eightfold), both precursors were repeatable in the short term
      (24 h), and plasma VTG was repeatable over a 14-d interval between successive
      breeding attempts.

PMID- 11331508
TI  - The maintenance nitrogen requirement of the zebra finch Taeniopygia guttata.
AB  - A procedure is described for the accurate determination of the maintenance
      nitrogen requirement (MNR) of small granivorous birds. When used with the zebra
      finch (Taeniopygia guttata), it yielded a MNR of 403 mg kgW(-0.75) d(-1). This is
      lower than most other passerines so far measured and more similar to some
      nonpasserine species. Similarly, the value for endogenous nitrogen loss estimated
      for the zebra finch (153 mg kgW(-0.75) d(-1)) is less than that for passerines in
      general but higher than the nonpasserine value. We suggest that the low MNR of
      the strictly granivorous zebra finch is primarily an adaptation to seed diets in
      which high-quality protein is a limiting factor. Comparison with a wider range of
      species reported in the literature was restricted because inappropriate methods
      have been used to estimate MNR in many cases, including the use of growing or
      reproducing birds and the assumption that maintenance of body mass necessarily
      coincides with maintenance of zero nitrogen balance.

PMID- 11331509
TI  - Serotonergic regulation of crustacean hyperglycemic hormone secretion in the
      crayfish, Procambarus clarkii.
AB  - These studies investigate if crustacean hyperglycemic hormone (CHH) is involved
      in 5-hydroxytryptamine (5-HT)-induced hyperglycemia. Eyestalk ganglia with intact
      X-organ-sinus gland complex were dissected from the crayfish Procambarus clarkii
      and incubated under various experimental conditions. Incubation media were then
      analyzed for the presence of released hyperglycemic factor using an in vivo
      bioassay. The results show that 5-HT enhanced release of hyperglycemic factor in
      a dose-dependent manner. This stimulatory effect of 5-HT was significantly
      decreased by adding ketanserin or methysergide (both 5-HT receptor antagonists)
      into incubation of eyestalk ganglia. Further, activity of the 5-HT-released
      hyperglycemic factor could be eliminated by adsorption of incubation media with
      anti-CHH serum but not by preimmune or anti-5-HT serum. These results confirm the
      hypothesis that 5-HT enhances release of CHH, which in turn elicits hyperglycemic
      responses. It is probable that 5-HT activates an excitation-secretion coupling
      mechanism by interacting with receptors located on the X-organ neurosecretory
      cells.

PMID- 11331510
TI  - Plasma cortisol concentrations before and after social stress in rainbow trout
      and brown trout.
AB  - Two related experiments examined the relationship between plasma cortisol
      concentrations and the development of social hierarchies in fish. In the first,
      rainbow trout, Oncorhynchus mykiss, and brown trout, Salmo trutta, were observed
      for dominance interactions when confined within single-species pairs for 4, 48,
      or 168 h. Subordinate members of a pair exhibited significantly higher cortisol
      concentrations than dominant and single fish, but the pattern of cortisol
      elevation differed between the two species, being quicker to rise and increasing
      to a higher level in rainbow trout. Cortisol concentrations were correlated with
      behavioural measurements; the more subordinate the behaviour exhibited by a fish,
      the higher its cortisol concentration. Social stress was a chronic stressor, and
      no acclimation to social status occurred during the week. In the second
      experiment, measurements of plasma cortisol were made before pairing of rainbow
      trout and then after 48 h of confinement in pairs. Subordinate fish demonstrated
      significantly higher concentrations of plasma cortisol both before and after
      social stress. It therefore appears that in addition to cortisol being elevated
      during periods of social stress, an association may exist between initial
      cortisol levels and the likelihood of a fish becoming subordinate.

PMID- 11331511
TI  - Aerobic capacity of frog skeletal muscle during hibernation.
AB  - Frogs submerged at 3 degrees C in hypoxic water (Po2=60 mmHg) depress their
      metabolic rate to 25% of that seen in control animals with access to air. The
      hypometabolic state of the skeletal muscle in such cold-submerged frogs is
      thought to be the most important contributor to the overall metabolic depression.
      The aim of this study was to determine whether the aerobic capacity of frog
      skeletal muscle became altered during 1-4 mo of hibernation to match the
      reduction in adenosine triphosphate (ATP) demand. To this end, the activities of
      key mitochondrial enzymes were measured in the skeletal muscle and in isolated
      mitochondria of frogs at different stages during hibernation. We also measured
      the activity of lactate dehydrogenase (LDH) as an indicator of glycolytic
      capacity. The activities of cytochrome c oxidase, citrate synthase, and LDH were
      significantly lower in frog skeletal muscle after 4 mo of hibernation compared
      with control conditions. The reduction in skeletal muscle aerobic capacity is
      apparently due to changes in the intrinsic properties of the mitochondria.
      Overall, these results indicate an important reorganisation of ATP-producing
      pathways during long-term metabolic depression to match the lowered ATP demand.

PMID- 11331512
TI  - Effect of age on seed digestion in parrots (Amazona aestiva).
AB  - The objective of this study was to compare the capacity of adult (more than 3 yr
      old) and young (less than 1 yr old) true parrots to digest seeds that are
      normally included in their diet in captivity, particularly soybean, sunflower,
      and corn. All the seeds were offered for 5 d with an interval of 15 d between
      different diets. The seeds of soybean and corn were boiled for 15 min and soaked
      in water at ambient temperature for 12 h before being fed to the birds. There
      were no differences in the digestibilities of crude protein and fats (ether
      extract) among animals, but the digestibilities of dry matter and crude fiber by
      the adult animals were higher than those of the young ones. The digestibility of
      carbohydrate (nitrogen-free extract) by adult birds was higher only for sunflower
      seeds. It is concluded that the capacity of parrots to digest fiber may change
      according to the age of the animal. Since the digestion of fiber depends on the
      action of microorganisms, these results suggest that the colonization of the
      gastrointestinal tract is delayed or very slow in young parrots.

PMID- 11331513
TI  - Effects of prolonged acclimation to cold on the extra--and intracellular acid
      base status in the land snail Helix lucorum (L.).
AB  - The aim of this study was to examine the effect of prolonged acclimation to cold
      on the acid-base status of extra- and intracellular fluids in the land snail
      Helix lucorum. For this purpose, acid-base parameters in the hemolymph and
      tissues were determined. In addition, the buffer values of hemolymph and tissues
      were determined in order to examine whether they change in the snails during
      acclimation to cold. According to the results presented, there is an inverse pH
      temperature relationship in the hemolymph within the first day of acclimation,
      which is consistent with alphastat regulation. The Pco2 decreased, and pH in the
      hemolymph (pH(e)) increased by 0.32 U within the first day of acclimation to
      cold, which corresponds to a change of 0.013 U degrees C(-1). After the first day
      of acclimation, Pco2 increased in the hemolymph, resulting in a significant drop
      in pH(e) by 90 d of acclimation to cold. Acclimation of snails to low
      temperatures did not change the buffer value of the hemolymph. Also,
      intracellular pH (pH(i)) and intracellular buffer values remained stable during
      acclimation to cold for prolonged periods. The latter results in conjunction with
      those obtained by the in vitro determination of the passive component of
      intracellular fluids indicate an active regulation of pH(i) in H. lucorum during
      acclimation to cold.

PMID- 11331514
TI  - Importance of glycolysis for the energetics of anoxia-tolerant and anoxia
      intolerant teleost hepatocytes.
AB  - The importance of glycolysis, as an ATP-producing and substrate-providing
      pathway, was studied in anoxia-tolerant (goldfish) and anoxia-intolerant (trout)
      hepatocytes. Inhibition of glycolysis with iodoacetic acid (IAA) left aerobic ATP
      production largely unaffected in hepatocytes from both species but caused a
      significant decrease of ATP contents in the goldfish cells. Ouabain-sensitive
      oxygen consumption (osVo2), an estimate of mitochondrial ATP production coupled
      to ATP consumption by the Na(+) pump, was significantly reduced in IAA-treated
      goldfish hepatocytes, whereas it was unaltered in trout hepatocytes. Partial
      reduction of mitochondrial respiration, achieved by titration with cyanide (CN),
      strongly stimulated glycolytic flux but did not affect ATP contents of
      hepatocytes from both species. Under these conditions, osVo2 became undetectable.
      Rb(+)-uptake rates, providing a direct estimate of Na(+)-pump activity, were in
      good agreement with estimates derived from osVo2 in IAA-treated cells, showing a
      decrease in goldfish and no change in trout. However, they indicated persistent
      Na(+)-pump activity despite the lack of osVo2 in CN-treated cells. Overall, these
      data indicate that in goldfish hepatocytes Na(+)-pump activity is more dependent
      on glycolytic ATP production as compared to trout hepatocytes. Protein synthesis
      of goldfish hepatocytes was inhibited in IAA- and CN-treated cells, possibly
      reflecting the hierarchical organization of energy metabolism. In trout
      hepatocytes, protein synthesis could be sustained at control levels, given that
      energetic substrate provision was not limited.

PMID- 11331515
TI  - Strategies of hypoxia and anoxia tolerance in cardiomyocytes from the
      overwintering common frog, Rana temporaria.
AB  - Using ventricular cardiomyocytes of the common frog, Rana temporaria, we
      investigated the metabolic strategies employed by the heart to tolerate 4 mo of
      hypoxic submergence (overwintering) as well as acute bouts of anoxia. In contrast
      to what is observed for the whole animal, there was no change in oxygen
      consumption in cardiomyocytes isolated from normoxic frogs compared with those
      isolated from 4-mo hypoxic animals. Furthermore, cells from both normoxic and
      hypoxic frogs were able to completely recover oxygen consumption following 30 min
      of acute anoxia. From estimates of ATP turnover, it appears that frog
      cardiomyocytes are capable of a profound, completely reversible metabolic
      depression, such that ATP turnover is reduced by >90% of control levels during
      anoxia but completely recovers with reoxygenation. Moreover, this phenomenon is
      also observed in frogs that have been subjected to 4 mo of extended hypoxia. We
      found a significant increase in the stress protein, hsp70, after 1 mo of hypoxic
      submergence, which may contribute to the heart's remarkable hypoxia and anoxia
      tolerance and may act to defend metabolism during the overwintering period.

PMID- 11331516
TI  - Chill-coma temperature in Drosophila: effects of developmental temperature,
      latitude, and phylogeny.
AB  - We modify and apply a nonlethal technique for rapidly quantifying the cold
      tolerance of large numbers of Drosophila and other small insects. Flies are
      transferred to individual vials, cooled in groups in progressive 0.5 degrees C
      steps, and checked for loss of righting response (chill-coma temperature
      [T(cc)]). Flies recover quickly when transferred to ambient temperature, and thus
      this technique potentially can be used in selection experiments. We applied this
      technique in several experiments. First, we examined the sensitivity of T(cc) to
      developmental temperature. Drosophila melanogaster (Congo, France), Drosophila
      subobscura (Spain, Denmark), and Drosophila ananassae (India) were reared from
      egg to adult at 15 degrees, 18 degrees, 25 degrees, or 29 degrees C, transferred
      to 15 degrees C for several days, and then progressively chilled: T(cc) was
      positively related to developmental temperature, inversely related to latitude of
      the population, but independent of sex. The sensitivity of T(cc) to developmental
      temperature (acclimation flexibility) was marked: T(cc) shifted on average 1
      degrees for each 4 degrees C shift in developmental temperature. Among 15 species
      of the obscura group of Drosophila, T(cc) varied from -0.1 degrees to 4.5 degrees
      C; T(cc) was inversely related to latitude in both nonphylogenetic and
      phylogenetically based ANCOVA (standardized independent contrasts) and was
      unrelated to body size.

PMID- 11331517
TI  - Is long-distance bird flight equivalent to a high-energy fast? Body composition
      changes in freely migrating and captive fasting great knots.
AB  - We studied changes in body composition in great knots, Calidris tenuirostris,
      before and after a migratory flight of 5,400 km from northwest Australia to
      eastern China. We also took premigratory birds into captivity and fasted them
      down to their equivalent arrival mass after migration to compare organ changes
      and nutrient use in a low-energy-turnover fast with a high-energy-turnover fast
      (migratory flight). Migrated birds were as economical as any fasting animal
      measured yet at conserving protein: their estimated relative protein contribution
      (RPC) to the energy used was 4.0%. Fasted birds had an estimated RPC of 6.8% and,
      consequently, a much lower lean mass and higher fat content for an equivalent
      body mass than migrated birds. Lean tissue was catabolized from most organs in
      both groups, except the brain. Furthermore, a principal components biplot showed
      that individuals were grouped primarily on the basis of overall organ fat or lean
      tissue content rather than by the size of specific organs. This indicates that
      organ changes during migratory flight are similar to those of a low-energy fast,
      although the length of the fast in this study probably accentuated organ
      reductions in some functional groups. Whether the metabolic characteristics of a
      flying migratory fast follow the three-phase model described in many inactive
      fasting animals is unclear. We have some evidence for skeletal fat being
      catabolized without phase 3 of a fast having been reached.

PMID- 11331518
TI  - Blood biochemistry reflects seasonal nutritional and reproductive constraints in
      the eurasian badger (Meles meles).
AB  - Physiological responses to nutritional and reproductive constraints were explored
      in a wild population of Eurasian badgers (Meles meles) inhabiting Wytham Woods,
      Oxfordshire, United Kingdom. We compared seasonal blood levels of lipid and
      protein compounds to variables describing the sex, age, body condition, wounds,
      testes position, and flea abundance of the badgers. We found seasonal variations
      in albumin/globulins and urea/creatinine ratios matched by differences in body
      condition. High creatinine, urea, and triglycerides levels were obtained in
      animals in poor nutritional condition and with low levels of body fat. The
      maintenance of urea/creatinine ratios indicates that the badger does not
      demonstrate a stage of protein conservation in periods of food scarcity during
      the summer or periods of cold weather. Hypercholesterolaemia, especially in fat
      animals, was confirmed. We also offer baseline levels of metabolites commonly
      used in clinical biochemistry for their further use in the analysis of the status
      and the management of wild badger populations.

PMID- 11331519
TI  - Renal response to dietary protein in the house sparrow Passer domesticus.
AB  - Many birds switch seasonally or during ontogeny between diets of varying protein
      content. In mammals, high-protein diets induce hypertrophy of the kidney in
      general and of the thick ascending limbs (TAL) in particular, along with
      increases in glomerular filtration rate (GFR) and urine flow. A hypothesis to
      explain these phenomena is that the TAL become increasingly sensitive to peptide
      hormones (glucagon and antidiuretic hormone [ADH]) released in response to
      protein feeding; the consequent enhancement of ion reabsorption dilutes urine
      reaching the macula densa, thereby suppressing tubulo-glomerular feedback (TGF)
      and causing a rise in GFR. Avian kidneys possess most of the elements involved in
      this mechanism, including loops of Henle with TAL, sensitivity of TAL to ADH
      (arginine vasotocin [AVT] in birds), and the elements of TGF. We therefore
      hypothesized that switching from a low-protein to a high-protein diet would
      induce responses in birds similar to those found in mammals. We tested this
      hypothesis by feeding house sparrows, Passer domesticus, isocaloric diets
      containing either 8% or 30% protein. Birds on high-protein food had larger renal
      medullae, both in mass and in TAL diameter, but no increase in whole-kidney mass.
      Urine flow was approximately doubled on high-protein food, but there was no
      change in GFR. We were not able to detect an increased sensitivity of AVT-induced
      adenylyl cyclase activity in TAL from high-protein animals, and responsiveness to
      glucagon was higher in TAL from birds eating low-protein food. We are unable to
      conclude that a suppression of TGF is responsible for the rise in urine flow in
      birds eating high-protein foods, and the mechanisms behind the medullary
      hypertrophy and the diuresis remain to be fully explored.

PMID- 11331520
TI  - Identifying neurons in the preBotzinger complex that generate respiratory rhythm:
      visualizing the ghost in the machine.

PMID- 11331521
TI  - Neurokinin-1 receptor-immunoreactive neurons of the ventral respiratory group in
      the rat.
AB  - The rostral end of the ventral respiratory group (VRG) contains neurons that are
      intensely neurokinin-1 receptor (NK1R) immunoreactive (ir). It has been theorized
      that some of these cells might be critical to respiratory rhythmogenesis (Gray et
      al. [1999] Science 286:1566-1568). In the present study we determined what major
      transmitter these NK1R-ir cells make and whether they are bulbospinal or
      propriomedullary. NK1R-ir neurons were found in the VRG between Bregma levels 
      11.7 and -13.6 mm. The highest concentration was found between Bregma -12.3 and 
      13.0 mm. This region overlaps with the pre-Botzinger complex (pre-BotC) as it was
      found to contain many pre-inspiratory neurons, few E2-expiratory neurons, and no
      I-incremental neurons. VRG NK1R-ir neurons contain neither tyrosine hydroxylase
      (TH) nor choline acetyl-transferase (ChAT) immunoreactivity, although dual
      labeled neurons were found elsewhere within the rostral medulla. GAD67 mRNA was
      commonly detected in the ventrolateral medulla (VLM) but rarely in the NK1R-ir
      neurons of the pre-BotC region (6 % of somatic profiles). GlyT2 mRNA was commonly
      found in the pre-BotC region but rarely within NK1R-ir neurons (1.3 %). Up to 40%
      of VRG NK1R-ir neurons were retrogradely labeled by Fluoro-Gold (FG) injected in
      the contralateral pre-BotC region. Some NK1R-ir VRG neurons located caudal to
      Bregma -12.6 mm were retrogradely labeled by FG injected in the spinal cord (C4
      C5, T2-T4). In sum, NK1R immunoreactivity is present in many types of ventral
      medullary neurons. Within the VRG proper, NK1R-ir neurons are concentrated in an
      area that overlaps with the pre-BotC. Within this limited region of the VRG, NK1R
      ir neurons are neither cholinergic nor catecholaminergic, and very few are gamma
      aminobutyric acid (GABA)ergic or glycinergic. The data suggest that most NK1R-ir
      neurons of the pre-BotC region are excitatory. Furthermore, the more rostral NK1R
      ir cells are propriomedullary, whereas some of the caudal ones project to the
      spinal cord.

PMID- 11331522
TI  - A role for cingulate pioneering axons in the development of the corpus callosum.
AB  - In many vertebrate and invertebrate systems, pioneering axons play a crucial role
      in establishing large axon tracts. Previous studies have addressed whether the
      first axons to cross the midline to from the corpus callosum arise from neurons
      in either the cingulate cortex (Koester and O'Leary [1994] J. Neurosci. 11:6608
      6620) or the rostrolateral neocortex (Ozaki and Wahlsten [1998] J. Comp. Neurol.
      400:197-206). However, these studies have not provided a consensus on which
      populations pioneer the corpus callosum. We have found that neurons within the
      cingulate cortex project axons that cross the midline and enter the contralateral
      hemisphere at E15.5. By using different carbocyanine dyes injected into either
      the cingulate cortex or the neocortex of the same brain, we found that cingulate
      axons crossed the midline before neocortical axons and projected into the
      contralateral cortex. Furthermore, the first neocortical axons to reach the
      midline crossed within the tract formed by these cingulate callosal axons, and
      appeared to fasciculate with them as they crossed the midline. These data
      indicate that axons from the cingulate cortex might pioneer a pathway for later
      arriving neocortical axons that form the corpus callosum. We also found that a
      small number of cingulate axons project to the septum as well as to the
      ipsilateral hippocampus via the fornix. In addition, we found that neurons in the
      cingulate cortex projected laterally to the rostrolateral neocortex at least 1
      day before the neocortical axons reach the midline. Because the rostrolateral
      neocortex is the first neocortical region to develop, it sends the first
      neocortical axons to the midline to form the corpus callosum. We postulate that,
      together, both laterally and medially projecting cingulate axons may pioneer a
      path for the medially directed neocortical axons, thus helping to guide these
      axons toward and across the midline during the formation of the corpus callosum.

PMID- 11331523
TI  - Distribution of galaninergic immunoreactivity in the brain of the mouse.
AB  - The distribution of galaninergic immunoreactive (-ir) profiles was studied in the
      brain of colchicine-pretreated and non-pretreated mice. Galanin (GAL)-ir neurons
      and fibers were observed throughout all encephalic vesicles. Telencephalic GAL-ir
      neurons were found in the olfactory bulb, cerebral cortex, lateral and medial
      septum, diagonal band of Broca, nucleus basalis of Meynert, bed nucleus of stria
      terminalis, amygdala, and hippocampus. The thalamus displayed GAL-ir neurons
      within the anterodorsal, paraventricular, central lateral, paracentral, and
      central medial nuclei. GAL-ir neurons were found in several regions of the
      hypothalamus. In the midbrain, GAL-ir neurons appeared in the pretectal olivary
      nucleus, oculomotor nucleus, the medial and lateral lemniscus, periaqueductal
      gray, and the interpeduncular nucleus. The pons contained GAL-ir neurons within
      the dorsal subcoeruleus, locus coeruleus, and dorsal raphe. In the medulla
      oblongata, GAL-ir neurons appear in the anterodorsal and dorsal cochlear nuclei,
      salivatory nucleus, A5 noradrenergic cells, gigantocellular nucleus, inferior
      olive, solitary tract nucleus, dorsal vagal motor and hypoglossal nuclei. Only
      GAL-ir fibers were seen in the lateral habenula nucleus, substantia nigra,
      parabrachial complex, cerebellum, spinal trigeminal tract, as well as the motor
      root of the trigeminal and facial nerves. GAL-ir was also observed in several
      circumventricular organs. The widespread distribution of galanin in the mouse
      brain suggests that this neuropeptide plays a role in the regulation of cognitive
      and homeostatic functions.

PMID- 11331524
TI  - Descending supraspinal pathways in amphibians. I. A dextran amine tracing study
      of their cells of origin.
AB  - The present study is the first of a series on descending supraspinal pathways in
      amphibians in which hodologic and developmental aspects are studied.
      Representative species of anurans (the green frog, Rana perezi, and the clawed
      toad, Xenopus laevis), urodeles (the Iberian ribbed newt, Pleurodeles waltl), and
      gymnophionans (the Mexican caecilian, Dermophis mexicanus) have been used. By
      means of retrograde tracing with dextran amines, previous data in anurans were
      largely confirmed and extended, but the studies in P. waltl and D. mexicanus
      present the first detailed data on descending pathways to the spinal cord in
      urodeles and gymnophionans. In all three orders, extensive brainstem-spinal
      pathways were present with only minor representation of spinal projections
      originating in forebrain regions. In the rhombencephalon, spinal projections
      arise from the reticular formation, several parts of the octavolateral area, the
      locus coeruleus, the laterodorsal tegmental nucleus, the raphe nucleus, sensory
      nuclei (trigeminal sensory nuclei and the dorsal column nucleus), and the nucleus
      of the solitary tract. In all species studied, the cerebellar nucleus and
      scattered cerebellar cells innervate the spinal cord, predominantly
      contralaterally. Mesencephalic projections include modest tectospinal
      projections, torospinal projections, and extensive tegmentospinal projections.
      The tegmentospinal projections include projections from the nucleus of Edinger
      Westphal, the red nucleus, and from anterodorsal, anteroventral, and
      posteroventral tegmental nuclei. In the forebrain, diencephalospinal projections
      originate in the ventral thalamus, posterior tubercle, the pretectal region, and
      the interstitial nucleus of the fasciculus longitudinalis medialis. The most
      rostrally located cells of origin of descending spinal pathways were found in the
      suprachiasmatic nucleus, the preoptic area and a subpallial region in the caudal
      telencephalic hemisphere, probably belonging to the amygdaloid complex. Our data
      are discussed in an evolutionary perspective.

PMID- 11331525
TI  - Descending supraspinal pathways in amphibians. II. Distribution and origin of the
      catecholaminergic innervation of the spinal cord.
AB  - Immunohistochemical studies with antibodies against tyrosine hydroxylase,
      dopamine, and noradrenaline have revealed that the spinal cord of anuran,
      urodele, and gymnophionan (apodan) amphibians is abundantly innervated by
      catecholaminergic (CA) fibers and terminals. Because intraspinal cells occur in
      all three orders of amphibians CA, it is unclear to what extent the CA
      innervation of the spinal cord is of supraspinal origin. In a previous study, we
      showed that many cell groups throughout the forebrain and brainstem project to
      the spinal cord of two anurans (the green frog, Rana perezi, and the clawed toad,
      Xenopus laevis), a urodele (the Iberian ribbed newt, Pleurodeles waltl), and a
      gymnophionan (the Mexican caecilian, Dermophis mexicanus). To determine the exact
      site of origin of the supraspinal CA innervation of the amphibian spinal cord,
      retrograde tracing techniques were combined with immunohistochemistry for
      tyrosine hydroxylase in the same sections. The double-labeling experiments
      demonstrated that four brain centers provide CA innervation to the amphibian
      spinal cord: 1.) the ventrolateral component of the posterior tubercle in the
      mammillary region, 2.) the periventricular nucleus of the zona incerta in the
      ventral thalamus, 3.) the locus coeruleus, and 4.) the nucleus of the solitary
      tract. This pattern holds for all three orders of amphibians, except for the CA
      projection from the nucleus of the solitary tract in gymnophionans. There are
      differences in the strength of the projections (based on the number of double
      labeled cells), but in general, spinal functions in amphibians are controlled by
      CA innervation from brain centers that can easily be compared with their
      counterparts in amniotes. The organization of the CA input to the spinal cord of
      amphibians is largely similar to that described for mammals. Nevertheless, by
      using a segmental approach of the CNS, a remarkable difference was observed with
      respect to the diencephalic CA projections.

PMID- 11331526
TI  - Structure and projections of white matter neurons in the postnatal rat visual
      cortex.
AB  - Transient contributions of subplate neurons to the initial development of the
      cortex are well-characterized, yet little data are available on a subpopulation
      of subplate neurons that persist in the white matter (WM) of the cerebral cortex
      across development. To characterize the WM neurons, differential interference
      contrast and Nomarski optics were used to visualize individual cells in the WM in
      slices of rat visual cortex at postnatal ages 9-23. Soma-dendritic morphology and
      local axonal projection patterns, including probable synaptic innervation sites
      of their axons, were identified by intracellular filling with biocytin during
      electrophysiologic recordings. Dendritic branches of all WM neurons,
      tripartitioned here into upper, middle, and deep divisions, extend throughout the
      WM and frequently into the overlying cortex. Axonal arborizations from most WM
      neurons, including apparent boutons, project into adjacent WM with many also
      innervating overlying cortical layers, whereas some project into the stratum
      oriens/alveus of the hippocampal formation. Processes of a subset of WM neurons
      appear to be confined to the WM itself. By using antimicrotubule associated
      protein (MAP2) immunostaining to quantify the density of WM neurons in rat visual
      cortex, we find that their overall numbers decrease to approximately 30% of
      initial levels during postnatal development. During this same developmental
      period, an increasing percentage of WM neurons contain the synthetic enzyme for
      nitric oxide, nitric oxide synthase (NOS), as evaluated by immunostaining. Thus,
      WM neurons that survive the initial perinatal period of cell death are positioned
      under the laminae of the maturing cortex to potentially modulate the integration
      of visual signals through either conventional synaptic or nonconventional
      (diffusible NO signaling) mechanisms.

PMID- 11331527
TI  - Early efferent innervation of the zebrafish lateral line.
AB  - We examined the efferent innervation of the lateral line in zebrafish larvae.
      Three efferent nuclei were previously reported for the posterior line, two in the
      hindbrain and one in the ventral hypothalamus. Here we show that the same three
      nuclei innervate the anterior line as well. The rhombencephalic neurons innervate
      either the anterior or the posterior line. The diencephalic neurons seem to
      innervate both lines as well as the ear. The diencephalic efferents are labeled
      by anti-tyrosine hydroxylase antibodies and probably use dopamine as a
      transmitter. They are among the very first catecholaminergic neurons to
      differentiate in the brain and extend branches into the lateral line system
      almost as soon as the latter forms. We discuss possible functions of the
      rhombencephalic and diencephalic efferents.

PMID- 11331528
TI  - Constitutive expression of heat shock protein HSP25 in the central nervous system
      of the developing and adult mouse.
AB  - Immunohistochemistry and in situ hybridization have been used to survey
      constitutive heat shock protein (HSP)25 expression in the brain and spinal cord
      of the developing and adult mouse. The data reveal both transient and sustained
      patterns of expression and demonstrate robust differences between mice and rats.
      During development, HSP25 is transiently expressed in neurons of the inferior
      colliculus, various thalamic subnuclei, and the majority of Purkinje cells in the
      cerebellum. Sustained expression into adulthood is seen in neurons of the cranial
      nerve nuclei, spinal cord motoneurons, median preoptic nucleus, and a subset of
      Purkinje cells. Differences in HSP25 expression between adult rats and mice
      include the somatic motor nuclei innervating the extraocular muscles, which are
      HSP25 immunoreactive only in the rat. Similar differences in HSP25 expression are
      seen during the development of the inferior colliculus, thalamus, and cerebellum,
      where expression is restricted to mice.

PMID- 11331529
TI  - The cell adhesion molecule BEN defines a prosensory patch in the developing avian
      otocyst.
AB  - The distribution of the cell adhesion molecule BEN in the developing chick inner
      ear is described. BEN is first detected in the otic placode at stage 11. As the
      placode begins to invaginate, BEN becomes concentrated in a ventromedial region
      extending from the anterior to the posterior end of the otic pit. BEN expression
      levels increase in this region as the pit closes to form the otocyst, and
      distinct boundaries become defined along the dorsal and ventral edges of the
      ventromedial band of BEN expression. BEN expression also becomes concentrated
      dorsally within the otic epithelium as the pit closes and is observed in the
      condensing otic ganglion. By stage 22, the ventromedial band of BEN expression
      splits into two distinct regions, a small caudal patch within which the posterior
      crista will develop, and a larger anterior patch. By stage 26, this larger
      anterior patch of cells expressing BEN becomes subdivided into five separate
      areas corresponding to the regions within which the anterior crista, the lateral
      crista, the utricle, the saccule, and both the basilar papilla and lagenar macula
      form. Hair cells only develop within these regions defined by BEN distribution.
      The data suggest that the ventromedial patch of BEN expression observed from
      stage 11 onwards defines a single sensory competent zone from which all sensory
      organs of the inner ear develop. BEN immunoreactivity in the inner ear declines
      after stage 38. In response to noise exposure, upregulation of BEN expression is
      mainly detected in regions of the posthatch papilla where the damage is severe
      and regenerating hair cells are not observed. The regenerating hair and
      supporting cells do not express BEN, highlighting a molecular difference between
      the processes of development and regeneration.

PMID- 11331531
TI  - Immunocytochemical analysis of basket cells in rat piriform cortex.
AB  - Basket cells, defined by axons that preferentially contact cell bodies, were
      studied in rat piriform (olfactory) cortex with antisera to gamma-aminobutyric
      acid (GABA)ergic markers (GABA, glutamate decarboxylase) and to peptides and
      calcium binding proteins that are expressed by basket cells. Detailed
      visualization of dendritic and axonal arbors was obtained by silver-gold
      enhancement of staining for vasoactive intestinal peptide (VIP), cholecystokinin
      (CCK), parvalbumin, and calbindin. Neuronal features were placed into five
      categories: soma-dendritic and axonal morphologies, laminar distributions of
      dendritic and axonal processes, and molecular phenotype. Although comparatively
      few forms were distinguished within each category, a highly varied co-expression
      of features from different categories produced a "combinatorial explosion" in the
      characteristics of individual neurons. Findings of particular functional interest
      include: dendritic distributions suggesting that somatic inhibition is mediated
      by feedforward as well as feedback pathways, axonal variations suggesting a
      differential shaping of the temporal aspects of somatic inhibition from different
      basket cells, evidence that different principal cell populations receive input
      from different combinations of basket cells, and a close association between
      axonal morphology and molecular phenotype. A finding of practical importance is
      that light microscopic measurements of boutons were diagnostic for the molecular
      phenotype and certain morphological attributes of basket cells. It is argued that
      the diversity in basket cell form in the piriform cortex, as in other areas of
      the cerebral cortex, reflects requirements for large numbers of specifically
      tailored inhibitory processes for optimal operation that cannot be met by a small
      number of rigidly defined neuronal populations.

PMID- 11331530
TI  - A new subdivision of anterior piriform cortex and associated deep nucleus with
      novel features of interest for olfaction and epilepsy.
AB  - The anterior part of the piriform cortex (the APC) has been the focus of cortical
      level studies of olfactory coding and associative processes and has attracted
      considerable attention as a result of a unique capacity to initiate generalized
      tonic-clonic seizures. Based on analysis of cytoarchitecture, connections, and
      immunocytochemical markers, a new subdivision of the APC and an associated deep
      nucleus are distinguished in the rat. As a result of its ventrorostral location
      in the APC, the new subdivision is termed the APC(VR). The deep nucleus is termed
      the pre-endopiriform nucleus (pEn) based on location and certain parallels to the
      endopiriform nucleus. The APC(VR) has unique features of interest for normal
      function: immunostaining suggests that it receives input from tufted cells in the
      olfactory bulb in addition to mitral cells, and it provides a heavy, rather
      selective projection from the piriform cortex to the ventrolateral orbital cortex
      (VLO), a prefrontal area where chemosensory, visual, and spatial information
      converges. The APC(VR) also has di- and tri-synaptic projections to the VLO via
      the pEn and the submedial thalamic nucleus. The pEn is of particular interest
      from a pathological standpoint because it corresponds in location to the
      physiologically defined "deep piriform cortex" ("area tempestas") from which
      convulsants initiate temporal lobe seizures, and blockade reduces ischemic damage
      to the hippocampus. Immunostaining revealed novel features of the pEn and APC(VR)
      that could alter excitability, including a near-absence of gamma-aminobutyric
      acid (GABA)ergic "cartridge" endings on axon initial segments, few
      cholecystokinin (CCK)-positive basket cells, and very low gamma-aminobutyric acid
      transporter-1 (GAT1)-like immunoreactivity. Normal functions of the APC(VR)-pEn
      may require a shaping of neuronal activity by inhibitory processes in a fashion
      that renders this region susceptible to pathological behavior.

PMID- 11331532
TI  - Unipolar brush cells form a glutamatergic projection system within the mouse
      cerebellar cortex.
AB  - Unipolar brush cells (UBCs) of the mammalian vestibulocerebellum receive mossy
      fiber projections primarily from the vestibular ganglion and vestibular nuclei.
      Recently, the axons of UBCs have been shown to generate an extensive system of
      cortex-intrinsic mossy fibers, which resemble traditional cerebellar mossy fiber
      afferents and synapse with granule cell dendrites and other UBCs. However, the
      neurotransmitter used by the UBC axon is still unknown. In this study, we used
      long-term organotypic slice cultures of the isolated nodulus (lobule X) from
      postnatal day 8 mouse cerebella to identify the neurotransmitter and receptors at
      synapses of the UBC axon terminals, relying on the notion that, in these
      cultures, all of the cortex-extrinsic fibers had degenerated during the first few
      days in vitro. Quantification of glutamate immunogold labeling showed that the
      UBC axon terminals have the same high gold-particle density as the glutamatergic
      parallel fiber varicosities. Furthermore, UBCs identified by calretinin
      immunoreactivity expressed the glutamate receptor subunits GluR2/3, NMDAR1, and
      mGluR2/3, like they do in the mature mouse cerebellum in situ. Evoked excitatory
      postsynaptic currents (EPSCs), spontaneous EPSCs, and burst discharges were
      demonstrated in UBCs and granule cells by patch-clamp recording. Both the evoked
      and spontaneous EPSCs were blocked by ionotropic glutamate receptor antagonists
      CNQX and D-AP5. We conclude that neurotransmission at the UBC axon terminals is
      glutamatergic. Thus, UBCs provide a powerful network of feedforward excitation
      within the granular layer, which may amplify vestibular signals and synchronize
      activity in clusters of functionally related granule cells which project
      vertically to patches of Purkinje cells.

PMID- 11331533
TI  - In vivo expression and localization of the fibroblast growth factor system in the
      intact and lesioned rat peripheral nerve and spinal ganglia.
AB  - Basic fibroblast growth factor (FGF-2) is involved in several cellular processes
      of the nervous system during development, maintenance, and regeneration. In the
      central nervous system, FGF-2 has been shown to be expressed in neurons and glial
      cells, depending on the developmental stage and brain area. In the present study,
      a comprehensive analysis was performed of the cellular distribution of the
      transcripts of FGF-2 and of the FGF high-affinity receptors (R) 1-4 in intact and
      lesioned sciatic nerve and spinal ganglia. In the adult rat sciatic nerve FGF-2,
      FGFR1-3 were expressed at low levels as revealed by reverse transcriptase
      polymerase chain reaction (RT-PCR). Sciatic nerve crush resulted in an increase
      of these transcript levels. FGFR4 expression was not detected in the intact and
      crushed nerve as revealed by RT-PCR and RNase protection assay. In situ
      hybridization using riboprobes for FGF-2, FGFR1-3 displayed staining in diverse
      cell types. Immunocytochemical staining of consecutive sections with cell markers
      for myelin, macrophages, and neurons revealed colocalization of the transcripts
      with Schwann cells and macrophages. In addition to FGF-2 and FGFR1, the
      transcripts of FGFR2-4 were expressed in neurons of spinal ganglia. Crush lesion
      of the sciatic nerve resulted in no alterations of the FGFR1-4 transcripts,
      whereas FGF-2 and FGFR3 mRNAs were up-regulated in spinal ganglia. The expression
      of FGFRs and FGF-2 in Schwann cells and macrophages at the lesion site of the
      sciatic nerve and in sensory neurons suggests that FGF-2 is involved in specific
      functions of these cells during regeneration.

PMID- 11331534
TI  - As the gut ages: timetables for aging of innervation vary by organ in the Fischer
      344 rat.
AB  - To explore the effects of aging on the vagal innervation of the gastrointestinal
      (GI) tract, male Fischer 344 rats at 3 and 24 months of age were injected in the
      left nodose ganglion with 3 microl of either 4% wheat germ agglutinin-horseradish
      peroxidase (to label sensory endings) or 1% cholera toxin subunit B-horseradish
      peroxidase (to label motor endings). The stomach and duodenum were prepared as
      wholemounts and processed with tetramethyl benzidine. In addition, to study age
      related changes in the myenteric plexus, the stomachs, small intestines, and
      large intestines from 3-, 12-, 21-, 24- and 27-month-old rats were prepared as
      wholemounts and processed with Cuprolinic Blue (to stain the neurons). Vagal
      afferent endings, motor terminal profiles, and myenteric neurons were counted and
      mapped with a sampling grid. In the stomach, both the vagal and myenteric
      innervation were stable between the ages of 3 and 24 months; however, a decrease
      in the number of myenteric neurons in the forestomach was noted at 27 months. In
      the small and large intestines, myenteric cell loss occurred by 12 months of age,
      progressed with age, and appeared to be governed by several general principles:
      (1) the rate of cell loss was organ-specific, with a gradient of increasing
      severity from proximal to distal in the gut; (2) within organs of the GI tract,
      the rate of cell loss differed between regions; and (3) for given regions, cell
      losses progressed linearly with increasing age. The findings suggest that a
      positive relationship exists between the density of vagal extrinsic innervation
      and myenteric neuron survival; however, whether this results from the vagal
      innervation and/or other factor(s) protecting or rescuing myenteric neurons from
      age-related attrition remains to be determined.

PMID- 11331536
TI  - Advances in the in vivo measurement of normal and abnormal carpal kinematics.
AB  - This article presents the development of an in vivo, three-dimensional
      methodology using markerless bone registration for examining the normal and
      abnormal kinematics of the wrist carpal bones. The resulting descriptions of
      three-dimensional kinematics from healthy patients and patients with documented
      unilateral scapholunate interosseous ligament injuries are briefly presented.

PMID- 11331535
TI  - The health care information directive.
AB  - BACKGROUND: Developments in information technology promise to revolutionise the
      delivery of health care by providing access to data in a timely and efficient
      way. Information technology also raises several important concerns about the
      confidentiality and privacy of health data. New and existing legislation in
      Europe and North America may make access to patient level data difficult with
      consequent impact on research and health surveillance. Although research is being
      conducted on technical solutions to protect the privacy of personal health
      information, there is very little research on ways to improve individuals power
      over their health information. This paper proposes a health care information
      directive, analogous to an advance directive, to facilitate choices regarding
      health information disclosure. RESULTS AND DISCUSSION: A health care information
      directive is described which creates a decision matrix that combines the ethical
      appropriateness of the use of personal health information with the sensitivity of
      the data. It creates a range of possibilities with in which individuals can
      choose to contribute health information with or without consent, or not to
      contribute information at all. CONCLUSION: The health care information directive
      may increase individuals understanding of the uses of health information and
      increase their willingness to contribute certain kinds of health information.
      Further refinement and evaluation of the directive is required.

PMID- 11331537
TI  - Arthroscopic and open management of dynamic scaphoid instability.
AB  - This article focuses on the pathophysiology and treatment of dynamic scaphoid
      instability. Cadaver studies suggest that dynamic instability results from
      isolated injury to the scapholunate interosseous ligament without damage to the
      dorsal intercarpal and dorsal radial lunotriquetral ligaments. The diagnosis may
      be made by dynamic fluoroscopic examination, including stress and load views. The
      role of arthroscopy is twofold: (1) it enables the surgeon to distinguish between
      a complete, grossly unstable scapholunate interosseous space that requires open
      treatment and (2) it permits direct visualization of the reduction and
      percutaneous pinning of the articulation in an effort to stabilize the joint.
      Operative indications, open and arthroscopic techniques, and results are
      discussed.

PMID- 11331538
TI  - Bone-retinaculum-bone reconstruction of scapholunate ligament injuries.
AB  - This article describes the indications for the use of a bone-retinaculum-bone
      autograft in soft tissue reconstruction of the torn scapholunate ligament.
      Specific surgical technique and postoperative management are highlighted. Initial
      results of a primary cohort of patients undergoing this technique are described.
      The technique is mainly indicated for patients with scapholunate ligament tears
      that are moderately easy to reduce by open methods.

PMID- 11331539
TI  - Arthroscopic reduction and percutaneous fixation of scaphoid fractures with a
      novel dorsal technique.
AB  - This article presents a technical description of a novel dorsal technique of
      arthroscopic reduction and percutaneous fixation of scaphoid fractures.
      Background highlighting the evolution of this technique is described. A series of
      patients treated in this manner, all of whom have healed without complications,
      is presented.

PMID- 11331540
TI  - Vascularized bone grafts for scaphoid nonunions and kienbock's disease.
AB  - Vascularized bone grafts offer the ability to transfer bone with viable
      osteoclasts and osteoblasts with a preserved circulation. The resultant primary
      bone healing without creeping substitution through necrotic bone is an attractive
      alternative to conventional bone grafting in aiding or accelerating healing,
      replacing deficient bone, and revascularizing necrotic bone. Recent advances in
      the anatomy and physiology of vascularized bone grafts have increased the
      understanding and ability to apply them to various of carpal maladies. This
      article focuses on the principles, anatomy, application, and experimental and
      clinical studies of vascularized bone grafts for the treatment of scaphoid
      nonunions and Kienbock's disease.

PMID- 11331541
TI  - Arthroscopic repair of triangular fibrocartilage complex injuries.
AB  - The triangular fibrocartilage complex is a functionally and anatomically
      intricate group of structures located at the ulnar aspect of the wrist. Injury to
      this structure affects the biomechanics of the wrist and makes functional
      restoration difficult. This article reviews the anatomy, biomechanics, diagnosis,
      and arthroscopic treatment of triangular fibrocartilage complex injuries.

PMID- 11331542
TI  - Diagnosis and management of acute fracture-dislocation of the carpus.
AB  - Acute fracture-dislocations of the carpus are uncommon. If treated inadequately,
      however, these injuries can lead to wrist pain and dysfunction as a result of
      progressive traumatic arthritis. Accurate diagnosis and early intervention are
      essential for optimal recovery. This article presents the anatomy, epidemiology,
      and mechanisms of injury of the carpus and the diagnosis, treatment, and
      treatment results of dislocation of the carpus.

PMID- 11331543
TI  - Treating fractures of the distal radius with arthroscopic assistance.
AB  - The role and technique of arthroscopy when used in the treatment of fractures of
      he distal radius are reviewed. Arthroscopy, if properly modified, assists in the
      evaluation and reduction of displaced intra-articular fractures of the distal
      radius in treating associated injuries within the carpus. Technical details
      important to the successful use of this technique are discussed. Favorable
      outcomes have been reported after the use of this technique for the reduction of
      displaced intra-articular fractures of the distal radius.

PMID- 11331544
TI  - Limited incision open techniques for distal radius fracture management.
AB  - This article discusses recent innovations in the management of distal radius
      fractures. Clinical and biomechanical studies have shown that stable fixation can
      be achieved with small implants aligned in an orthogonal fashion. This technique
      greatly diminishes the necessary soft tissue dissection needed at surgery and
      allows for early mobilization of the wrist, which may lead to improved outcomes
      and fewer soft tissue complications.

PMID- 11331545
TI  - Five-pin external fixation and early range of motion for distal radius fractures.
AB  - One of the continuing dilemmas in the treatment of distal radius fractures is how
      best to reduce residual dorsal angulation and impacted articular fragments.
      Although external fixation devices may maintain radial length, individual
      fracture fragments may still heal in a displaced or angulated position. The
      addition of a dorsal pin in combination with an external fixation device can
      easily correct the dorsal tilt found in many fractures of the distal radius.
      Although not necessary in all fractures, this additional pin helped with
      reduction of those fractures that would not improve with traction and with
      maintenance of reduction.

PMID- 11331546
TI  - The role of bone graft and alternatives in unstable distal radius fracture
      treatment.
AB  - The increased prevalence of unstable fractures of the distal radius has
      stimulated the development of new technologies and new surgical techniques for
      treating these complex injuries. New developments also contribute to the
      expectation that orthopedic surgeons should be able to treat the fractured distal
      radius more successfully by achieving early stability, early function, and better
      outcomes. The continuous introduction of commercial bone graft substitutes and
      graft extenders has provided a large array of implantable materials. Rigorous
      comparison of the commercially available bone graft substitutes is difficult not
      only because of their diversity but also because uniformly accepted preclinical
      assays and comparable clinical studies have not been performed. Despite the lack
      of complete data, however, available data and collective experience suggest that
      bone graft substitutes can provide improved treatment methods and outcomes.

PMID- 11331547
TI  - Reconstruction of the posttraumatic unstable distal radioulnar joint.
AB  - Although not a common problem, the posttraumatic unstable distal radioulnar joint
      can be difficult to treat. This article focuses on the various methods for
      reconstruction of the unstable distal radioulnar joint. Attention focuses
      specifically on anatomic reconstruction of distal radioulnar ligaments. The
      authors' technique is presented in detail.

PMID- 11331548
TI  - Distal ulnar prosthetic replacement.
AB  - A stable, functioning distal radioulnar joint not only provides supination and
      pronation of the forearm but also is essential to gripping and lifting.
      Therefore, when distal radioulnar joint deterioration occurs, proper repair is
      crucial. Ulnar head resection typically is performed; however, a prosthesis may
      be needed to replace all or part of the joint. This article discusses the
      advantages and disadvantages of four prostheses, including a total joint
      replacement designed by the authors.

PMID- 11331549
TI  - Gene therapy for neurodegenerative diseases: fact or fiction?

PMID- 11331550
TI  - Endophenotypes and child psychiatry.

PMID- 11331551
TI  - Informed consent in psychiatric research.

PMID- 11331552
TI  - Tryptophan depletion and its implications for psychiatry.
AB  - BACKGROUND: Over the past 10 years the technique of tryptophan depletion has been
      used increasingly as a tool for studying brain serotonergic systems. AIMS: To
      review the technique of tryptophan depletion and its current status as a tool for
      investigating psychiatric disorders. METHOD: Systematic review of preclinical and
      clinical studies. RESULTS: Tryptophan depletion produces a marked reduction in
      plasma tryptophan and consequently brain serotonin (5-HT) synthesis and release.
      In healthy volunteers the effects of tryptophan depletion are influenced by the
      characteristics of the subjects and include some mood lowering, some memory
      impairment and an increase in aggression. In patients with depression tryptophan
      depletion tends to result in no worsening of depression in untreated subjects but
      a relapse in those who have responded to antidepressants (particularly
      serotonergic agents). In panic disorder the results are similar. CONCLUSIONS: The
      findings that tryptophan depletion produces a relapse of symptoms in patients
      with depression and panic disorder who have responded to treatment with
      antidepressants suggests that enhanced 5-HT function is important in maintaining
      response in these conditions.

PMID- 11331553
TI  - International representation in psychiatric literature: survey of six leading
      journals.
AB  - BACKGROUND: Despite the growing recognition of the global burden of psychiatric
      disease, there are questions about the strength of the evidence base from non
      Western societies. AIMS: To compare the contribution of Euro-American countries
      and the rest of the world (RoW) to psychiatric literature. METHOD: Survey of the
      country of origin of papers submitted to and published in six leading psychiatric
      journals over a 3-year period (1996-1998). RESULTS: Only 6% of the literature is
      published from regions of the world that account for over 90% of global
      population. The three journals published in Europe had a significantly higher
      proportion of international articles when compared to the three American
      journals. Less than 1% of all published articles described mental health
      interventions in the ROW: Acceptance rates were significantly lower for papers
      submitted from the ROW: CONCLUSIONS: There is a gross under-representation of
      research from the ROW: This has implications for the development of a truly
      international psychiatry.

PMID- 11331554
TI  - Invited commentaries on: International representation in psychiatric literature.
      Survey of six leading journals. Can we learn from each other?

PMID- 11331555
TI  - Invited commentaries on: International representation in psychiatric literature.
      Survey of six leading journals. An inequity and its possible remedies.

PMID- 11331556
TI  - Structural brain abnormalities associated with deletion at chromosome 22q11:
      quantitative neuroimaging study of adults with velo-cardio-facial syndrome.
AB  - BACKGROUND: Velo-cardio-facial syndrome (VCFS) is associated with deletions in
      the qll band of chromosome 22, learning disability and psychosis, but the
      neurobiological basis is poorly understood. AIMS: To investigate brain anatomy in
      adults with VCFS. METHOD: Magnetic resonance imaging was used to study 10
      patients with VCFS and 13 matched controls. We carried out three analyses:
      qualitative; traced regional brain volume; and measurement of grey and white
      matter volume. RESULTS: The subjects with VCFS had: a high prevalence of white
      matter hyperintensities and abnormalities of the septum pellucidum; a
      significantly smaller volume of cerebellum; and widespread differences in white
      matter bilaterally and regional specific differences in grey matter in the left
      cerebellum, insula, and frontal and right temporal lobes. CONCLUSIONS: Deletion
      at chromosome 22q11 is associated with brain abnormalities that are most likely
      neurodevelopmental and may partially explain the high prevalence of learning
      disability and psychiatric disorder in VCFS.

PMID- 11331557
TI  - Predictors of later schizophrenia and affective psychosis among attendees at a
      child psychiatry department.
AB  - BACKGROUND: Schizophrenia has been linked with psychological problems in
      childhood but there is little information on precursors of affective psychosis.
      AIMS: To compare childhood psychological antecedents of adult schizophrenia and
      affective psychosis. METHOD: Childhood item sheets, which give standardised
      information on signs and symptoms of mental illness in the year preceding
      assessment are completed for all attendees at the children's department of the
      Maudsley and Bethlem Royal Hospital. We examined item sheet data on individuals
      with an adult diagnosis of schizophrenia (n=59) or affective psychosis (n=27) and
      a comparison group with no adult mental illness (n=86) (all had attended the
      department). RESULTS: Abnormal suspiciousness or sensitivity and relationship
      difficulties with peers are associated with later schizophrenia. In contrast,
      affective psychosis is associated with childhood hysterical symptoms and
      disturbances in eating. CONCLUSIONS: Childhood psychological precursors for
      schizophrenia and affective psychosis differ and do not simply reflect non
      specific psychiatric disturbance in adolescence.

PMID- 11331558
TI  - Psychosocial characteristics and needs of mothers with psychotic disorders.
AB  - BACKGROUND: It is not known whether mothers with psychotic disorders are
      clinically and socially distinct from women with psychoses who have not had
      children. AIMS: To determine the proportion of mothers in an epidemiologically
      representative population of women with psychotic disorders, to examine the
      factors associated with having children, and to examine the factors associated
      with having children 'looked after' by social services. METHOD: Descriptive
      analysis and two case-control studies. RESULTS: Sixty-three per cent of women
      with psychotic disorders were mothers. There were no clinical differences between
      women with or without children, but mothers were more likely to be older and live
      in unsupported accommodation. Having had a 'looked after' child was associated
      with Mental Health Act detention, younger age, a forensic history and being Black
      African. CONCLUSION: Many women with psychoses are mothers. Mothers with
      psychoses are as disabled and have as many needs as women with psychoses without
      children.

PMID- 11331559
TI  - Aggressive incidents in first-episode psychosis.
AB  - BACKGROUND: Recent research has reported increased risk of aggressive incidents
      by individuals with psychotic illness. AIMS: To examine acts of aggression in
      first-episode psychosis. METHOD: Subjects with a first-episode psychosis were
      ascertained from a defined catchment area (Nottingham, UK) and reassessed at 3
      years (n=166) using clinical interview, informants, health care and forensic
      records. RESULTS: Of the subjects, 9.6% demonstrated at least one act of serious
      aggression (defined as weapon use, sexual assault or victim injury) during at
      least one psychotic episode and 23.5% demonstrated lesser acts of aggression
      (defined as all other acts of aggression). For all aggressive subjects (33.1%),
      unemployment (OR=3.6, 95% C11.6-8.0), comorbid substance misuse (OR=3.1, C1 1.1
      8.8) and symptoms of overactivity at service contact (OR=6.9,C1 2.7-17.8) had
      independent effects on risk of aggression. CONCLUSIONS: We confirmed some
      previously reported demographic and clinical associations with aggression in
      first-episode psychosis but no relationship with specific psychotic symptoms or
      diagnostic groups was observed.

PMID- 11331560
TI  - Factors that influence the cost of caring for patients with severe psychotic
      illness: report from the UK 700 trial.
AB  - BACKGROUND: Many factors influence the type and quantity of services received by
      patients and, thus, the total cost of care. Knowledge of these factors can aid
      budgetary and service-planning decisions. AIMS: To investigate factors that
      influence the cost of caring for patients with severe psychotic illness. METHOD:
      Univariate and multivariate analyses were used to examine associations between
      baseline characteristics and subsequent 2-year total direct costs in 667 patients
      from the UK 700 case management trial. RESULTS: Significantly more money was
      spent on younger patients, those with longer duration of illness, those who had
      spent less time living independently and those who had spent longer in hospital
      for psychiatric reasons. CONCLUSIONS: Total costs of caring for patients with
      severe psychotic illness appear to be influenced to a large extent by age,
      duration of illness and past levels of dependence on statutory services. The
      strength of these relationships is greater than the impact of illness severity.

PMID- 11331561
TI  - Effects of rapid tryptophan depletion on brain 5-HT(2) receptors: a PET study.
AB  - BACKGROUND: The mechanism by which rapid tryptophan depletion (RTD) paradigm
      induces depressive relapse in recently remitted patients with depression is
      unknown. AIMS: To determine the effects of RTD on brain 5-HT(2) receptors using
      positron emission tomography (PET) and (18)F-labelled setoperone. METHOD: Ten
      healthy women under went two PET scans. Each scan was done 5 h after the
      ingestion of either a balanced or a tryptophan-deficient amino acid mixture, and
      the two test sessions were separated by at least 5 days. RESULTS: The RTD
      decreased plasma free tryptophan levels significantly but it had no significant
      effects on mood. Subjects showed a significant decrease in brain 5-HT(2) receptor
      binding in various cortical regions following the RTD session. CONCLUSIONS: When
      taken with the evidence that antidepressant treatment is associated with a
      decrease in brain 5-HT(2) receptors, these findings suggest that a decrease in 5
      HT(2) binding following RTD might be an adaptive response that provides
      protection against depressive symptoms.

PMID- 11331562
TI  - Decreased sensitivity of 5-HT(1D) receptors in melancholic depression.
AB  - BACKGROUND: Brain serotonin (5-HT) function is abnormal in major depression, but
      the involvement of different 5-HT receptor subtypes has been little studied. The
      availability of selective ligands now makes it possible to test the sensitivity
      of 5-HT(1D) receptors in patients with depression. AIMS: The aim of the study was
      to use the 5-HT(1D) receptor agonist, zolmitriptan, to test the sensitivity of 5
      HT(1D) receptors in patients with depression before and after treatment with
      selective serotonin reuptake inhibitors (SSRIs). METHOD: We measured the growth
      hormone response to zolmitriptan (5 mg orally) in patients with major depression
      before and after SSRI treatment. A matched sample of healthy subjects acted as a
      control group. RESULTS: The growth hormone response to zolmitriptan was blunted
      in patients with a melancholic depressive syndrome. SSRI treatment produced a
      marked reduction in zolmitriptan-induced growth hormone release. CONCLUSIONS:
      Patients with melancholic depression have impaired sensitivity of the post
      synaptic 5-HT(1D) receptors that mediate growth hormone release. The reduction in
      5-HT(1D) receptor sensitivity following SSRI treatment is probably an adaptive
      response to increased levels of synaptic 5-HT.

PMID- 11331563
TI  - Relationship of suicide rates to social factors and availability of lethal
      methods: comparison of suicide in Newcastle upon Tyne 1961-1965 and 1985-1994.
AB  - BACKGROUND: The UK Government's White Paper Saving Lives: Our Healthier Nation
      included among its targets a reduction in suicide. AIMS: To study causes of
      change in suicide rate over a 30-year period in Newcastle upon Tyne. METHOD:
      Suicide rates and methods, based on coroners' inquest records, were compared over
      two periods (1961-1965 and 1985-1994) and differences were related to changes in
      exposure to poisions and prescribed drugs, and to socio-demographic changes.
      RESULTS: Demographic and social changes had taken place which would adversely
      affect suicide rates. However, a dramatic fall was found in the rate for women,
      and a modest decline in that for men. Reduced exposure to carbon monoxide and to
      barbiturates coincided with the fall in rates. CONCLUSIONS: Reduced exposure to
      lethal methods was responsible for the fall in rate in both genders, while the
      gender difference in favour of women may be related to their preference for non
      violent methods or to their being less affected by the social changes.

PMID- 11331564
TI  - Open verdict v. suicide - importance to research.
AB  - BACKGROUND: Open verdicts are often included in with suicides for research
      purposes and for setting health targets. AIMS: To examine similarities and
      differences in cases defined by the coroner as suicide and open verdicts and the
      implications of open verdicts for suicide research. METHOD: All cases of open and
      suicide verdicts recorded in the Newcastle Coroner's Court in the period 1985
      1994 were compared on demographic and medical parameters. RESULTS: Open and
      suicide verdicts had many similarities, differing only in some respects, of which
      logistic regression identified the most significant to be a suicide note, method
      used and age. CONCLUSIONS: Open verdicts should be included in all suicide
      research after excluding cases in which suicide was unlikely. Objective criteria
      are needed to facilitate comparison between different studies.

PMID- 11331565
TI  - Suicide in children and adolescents in England and Wales 1970-1998.
AB  - BACKGROUND: Suicide rates for England and Wales have been decreasing recently,
      but rates for young adult males remain high. AIMS: To review changes in suicide
      rates for children and adolescents in England and Wales between 1970 and 1998.
      METHOD: Rates for suicide, 'accidental' death by causes similar to suicide and
      'undetermined' death for 10-14- and 15-19-year-olds are calculated between 1970
      and 1998 using suicide data and estimated mid-year populations obtained from the
      Office for National Statistics. RESULTS: There has been a substantial increase in
      suicide rate between the 1970s and the 1990s for males aged 15-19 years. This
      remains true even when 'undetermined' and 'accidental' death rates for causes
      similar to suicide are examined. The increase was associated with an increase in
      self-poisoning with vehicle exhaust gas in the 1980s and an increase in hanging
      which has continued into the 1990s. Although there was a slight decrease in the
      official suicide rate for females aged 15-19 years, 'undetermined' deaths
      increased. There is no indication of a major change in suicide rate in 10-14-year
      olds. CONCLUSIONS: The substantial increase in suicide rate in 15-19-year-old
      males may indicate increased psychosocial stress, particularly affecting this
      group.

PMID- 11331566
TI  - Common mental disorders in urban v. rural Pakistan.

PMID- 11331567
TI  - Continuing stigmatisation by psychiatrists.

PMID- 11331568
TI  - Prevalence of depression in old age.

PMID- 11331569
TI  - Cognitive therapy and social functioning in chronic depression.

PMID- 11331570
TI  - Antidepressants and suicide risk.

PMID- 11331571
TI  - Psychodynamic thinking and the community mental health team.

PMID- 11331572
TI  - What came first: dimensions or categories?

PMID- 11331573
TI  - Long-term psychotherapeutic relationships in schizophrenia.

PMID- 11331574
TI  - Classic text still accessible.

PMID- 11331575
TI  - Practical application of structured risk assessment.

PMID- 11331576
TI  - Loss of memory and of sense of personal identity.

PMID- 11331577
TI  - Oligopeptide repeats in the yeast protein Sup35p stabilize intermolecular prion
      interactions.
AB  - The nuclear-encoded Sup35p protein is responsible for the prion-like [PSI(+)]
      determinant of yeast, with Sup35p existing largely as a high molecular weight
      aggregate in [PSI(+)] strains. Here we show that the five oligopeptide repeats
      present at the N-terminus of Sup35p are responsible for stabilizing aggregation
      of Sup35p in vivo. Sequential deletion of the oligopeptide repeats prevented the
      maintenance of [PSI(+)] by the truncated Sup35p, although deletants containing
      only two repeats could be incorporated into pre-existing aggregates of wild-type
      Sup35p. The mammalian prion protein PrP also contains similar oligopeptide
      repeats and we show here that a human PrP repeat (PHGGGWGQ) is able functionally
      to replace a Sup35p oligopeptide repeat to allow stable [PSI(+)] propagation in
      vivo. Our data suggest a model in which the oligopeptide repeats in Sup35p
      stabilize intermolecular interactions between Sup35p proteins that initiate
      establishment of the aggregated state. Modulating repeat number therefore alters
      the rate of yeast prion conversion in vivo. Furthermore, there appears to be
      evolutionary conservation of function of the N-terminally located oligopeptide
      repeats in prion propagation.

PMID- 11331578
TI  - Glycoprotein VI but not alpha2beta1 integrin is essential for platelet
      interaction with collagen.
AB  - Platelet adhesion on and activation by components of the extracellular matrix are
      crucial to arrest post-traumatic bleeding, but can also harm tissue by occluding
      diseased vessels. Integrin alpha2beta1 is thought to be essential for platelet
      adhesion to subendothelial collagens, facilitating subsequent interactions with
      the activating platelet collagen receptor, glycoprotein VI (GPVI). Here we show
      that Cre/loxP-mediated loss of beta1 integrin on platelets has no significant
      effect on the bleeding time in mice. Aggregation of beta1-null platelets to
      native fibrillar collagen is delayed, but not reduced, whereas aggregation to
      enzymatically digested soluble collagen is abolished. Furthermore, beta1-null
      platelets adhere to fibrillar, but not soluble collagen under static as well as
      low (150 s(-1)) and high (1000 s(-1)) shear flow conditions, probably through
      binding of alphaIIbbeta3 to von Willebrand factor. On the other hand, we show
      that platelets lacking GPVI can not activate integrins and consequently fail to
      adhere to and aggregate on fibrillar as well as soluble collagen. These data show
      that GPVI plays the central role in platelet-collagen interactions by activating
      different adhesive receptors, including alpha2beta1 integrin, which strengthens
      adhesion without being essential.

PMID- 11331579
TI  - Cooperation between actin-binding proteins of invasive Salmonella: SipA
      potentiates SipC nucleation and bundling of actin.
AB  - Pathogen-induced remodelling of the host cell actin cytoskeleton drives
      internalization of invasive Salmonella by non-phagocytic intestinal epithelial
      cells. Two Salmonella actin-binding proteins are involved in internalization:
      SipC is essential for the process, while SipA enhances its efficiency. Using
      purified SipC and SipA proteins in in vitro assays of actin dynamics and F-actin
      bundling, we demonstrate that SipA stimulates substantially SipC-mediated
      nucleation of actin polymerization. SipA additionally enhances SipC-mediated F
      actin bundling, and SipC-SipA collaboration generates stable networks of F-actin
      bundles. The data show that bacterial SipC and SipA cooperate to direct efficient
      modulation of actin dynamics, independently of host cell proteins. The ability of
      SipA to enhance SipC-induced reorganization of the actin cytoskeleton in vivo was
      confirmed using semi-permeabilized cultured mammalian cells.

PMID- 11331580
TI  - The tripartite motif family identifies cell compartments.
AB  - A functional genomic approach, based on systematic data gathering, was used to
      characterize a family of proteins containing a tripartite motif (TRIM). A total
      of 37 TRIM genes/proteins were studied, 21 of which were novel. The results
      demonstrate that TRIM proteins share a common function: by means of homo
      multimerization they identify specific cell compartments.

PMID- 11331581
TI  - Allosteric interactions between GB1 and GB2 subunits are required for optimal
      GABA(B) receptor function.
AB  - Recent studies on G-protein-coupled receptors revealed that they can dimerize.
      However, the role of each subunit in the activation process remains unclear. The
      gamma-amino-n-butyric acid type B (GABA(B)) receptor is comprised of two
      subunits: GB1 and GB2. Both consist of an extracellular domain (ECD) and a
      heptahelical domain composed of seven transmembrane alpha-helices, loops and the
      C-terminus (HD). Whereas GB1 ECD plays a critical role in ligand binding, GB2 is
      required not only to target GB1 subunit to the cell surface but also for receptor
      activation. Here, by analysing chimeric GB subunits, we show that only GB2 HD
      contains the determinants required for G-protein signalling. However, the HD of
      GB1 improves coupling efficacy. Conversely, although GB1 ECD is sufficient to
      bind GABA(B) ligands, the ECD of GB2 increases the agonist affinity on GB1, and
      is necessary for agonist activation of the receptor. These data indicate that
      multiple allosteric interactions between the two subunits are required for wild
      type functioning of the GABA(B) receptor and highlight further the importance of
      the dimerization process in GPCR activation.

PMID- 11331582
TI  - Modulation of integrin signal transduction by ILKAP, a protein phosphatase 2C
      associating with the integrin-linked kinase, ILK1.
AB  - ILKAP, a protein serine/threonine (S/T) phosphatase of the PP2C family, was
      isolated in a yeast two-hybrid screen baited with integrin-linked kinase, ILK1.
      Association of ILK1 and ILKAP was independent of the catalytic activity of either
      partner, as assayed in co-precipitation and two-hybrid experiments. Condi tional
      expression of ILKAP in HEK 293 cells resulted in selective inhibition of ECM- and
      growth factor-stimulated ILK1 activity, but did not inhibit Raf-1 kinase
      activity. A catalytic mutant of ILKAP, H154D, did not inhibit ILK1 kinase
      activity. Two cellular targets of ILK1, glycogen synthase kinase 3 beta
      (GSK3beta) and protein kinase B (PKB)/AKT, were differentially affected by ILKAP
      mediated inhibition of ILK1. Catalytically active, but not mutant ILKAP, strongly
      inhibited insulin-like growth factor-1-stimulated GSK3beta phosphorylation on
      Ser9, but did not affect phosphorylation of PKB on Ser473, suggesting that ILKAP
      selectively affects ILK-mediated GSK3beta signalling. Consistent with this,
      active, but not H154D mutant or the related PP2Calpha, selectively inhibited
      transactivation of a Tcf/Lef reporter gene, TOPFlash, in 293 cells. We propose
      that ILKAP regulates ILK1 activity, targeting ILK1 signalling of Wnt pathway
      components via modulation of GSK3beta phosphorylation.

PMID- 11331583
TI  - cdc42 regulates the exit of apical and basolateral proteins from the trans-Golgi
      network.
AB  - It is well established that Rho-GTPases regulate vesicle fusion and fission
      events at the plasma membrane through their modulatory role on the cortical actin
      cytoskeleton. In contrast, their effects on intracellular transport processes and
      actin pools are less clear. It was recently shown that cdc42 associates with the
      Golgi apparatus in an ARF-dependent manner, similarly to coat proteins involved
      in vesicle formation and to several actin-binding proteins. We report here that
      mutants of cdc42 inhibited the exit of basolateral proteins from the trans-Golgi
      network (TGN), while stimulating the exit of an apical marker, in two different
      transport assays. This regulation may result from modulation of the actin
      cytoskeleton, as GTPase-deficient cdc42 depleted a perinuclear actin pool that
      rapidly exchanges with exogenous fluorescent actin.

PMID- 11331584
TI  - The sortilin cytoplasmic tail conveys Golgi-endosome transport and binds the VHS
      domain of the GGA2 sorting protein.
AB  - Sortilin belongs to a growing family of multiligand type-1 receptors with
      homology to the yeast receptor Vps10p. Based on structural features and
      sortilin's intracellular predominance, we have proposed it to be a sorting
      receptor for ligands in the synthetic pathway as well as on the cell membrane. To
      test this hypothesis we examine here the cellular trafficking of chimeric
      receptors containing constructs of the sortilin tail. We report that sorting
      signals conforming to YXX and dileucine motifs mediate rapid endocytosis of
      sortilin chimeras, which subsequently travel to the trans-Golgi network, showing
      little or no recycling. Furthermore, we found that cation-independent mannose 6
      phosphate receptor (MPR300)-sortilin chimeras, expressed in mannose 6-phosphate
      receptor knockout cells, were almost as efficient as MPR300 itself for transport
      of newly synthesized beta-hexosaminidase and beta-glucuronidase to lysosomes, and
      established that the sortilin tail contains potent signals for Golgi-endosome
      sorting. Finally, we provide evidence suggesting that sortilin is the first
      example of a mammalian receptor targeted by the recently described GGA family of
      cytosolic sorting proteins, which condition the Vps10p-mediated sorting of yeast
      carboxypeptidase Y.

PMID- 11331585
TI  - PACS-1 binding to adaptors is required for acidic cluster motif-mediated protein
      traffic.
AB  - PACS-1 is a cytosolic protein involved in controlling the correct subcellular
      localization of integral membrane proteins that contain acidic cluster sorting
      motifs, such as furin and human immunodeficiency virus type 1 (HIV-1) NEF: We
      have now investigated the interaction of PACS-1 with heterotetrameric adaptor
      complexes. PACS-1 associates with both AP-1 and AP-3, but not AP-2, and forms a
      ternary complex between furin and AP-1. A short sequence within PACS-1 that is
      essential for binding to AP-1 has been identified. Mutation of this motif yielded
      a dominant-negative PACS-1 molecule that can still bind to acidic cluster motifs
      on cargo proteins but not to adaptor complexes. Expression of dominant-negative
      PACS-1 causes a mislocalization of both furin and mannose 6-phosphate receptor
      from the trans-Golgi network, but has no effect on the localization of proteins
      that do not contain acidic cluster sorting motifs. Furthermore, expression of
      dominant-negative PACS-1 inhibits the ability of HIV-1 Nef to downregulate MHC-I.
      These studies demonstrate the requirement for PACS-1 interactions with adaptor
      proteins in multiple processes, including secretory granule biogenesis and HIV-1
      pathogenesis.

PMID- 11331586
TI  - SNAREs are concentrated in cholesterol-dependent clusters that define docking and
      fusion sites for exocytosis.
AB  - During exocytosis, SNARE proteins of secretory vesicles interact with the
      corresponding SNARE proteins in the plasmalemma to initiate the fusion reaction.
      However, it is unknown whether SNAREs are uniformly distributed in the membrane
      or whether specialized fusion sites exist. Here we report that in the
      plasmalemma, syntaxins are concentrated in 200 nm large, cholesterol-dependent
      clusters at which secretory vesicles preferentially dock and fuse. The syntaxin
      clusters are distinct from cholesterol-dependent membrane rafts since they are
      Triton X-100-soluble and do not co-patch with raft markers. Synaptosomal
      associated protein (SNAP)-25 is also clustered in spots, which partially overlap
      with syntaxin. Cholesterol depletion causes dispersion of these clusters, which
      is associated with a strong reduction in the rate of secretion, whereas the
      characteristics of individual exocytic events are unchanged. This suggests that
      high local concentrations of SNAREs are required for efficient fusion.

PMID- 11331587
TI  - Patched1 interacts with cyclin B1 to regulate cell cycle progression.
AB  - The initiation of mitosis requires the activation of M-phase promoting factor
      (MPF). MPF activation and its subcellular localization are dependent on the
      phosphorylation state of its components, cdc2 and cyclin B1. In a two-hybrid
      screen using a bait protein to mimic phosphorylated cyclin B1, we identified a
      novel interaction between cyclin B1 and patched1 (ptc1), a tumor suppressor
      associated with basal cell carcinoma (BCC). Ptc1 interacted specifically with
      constitutively phosphorylated cyclin B1 derivatives and was able to alter their
      normal subcellular localization. Furthermore, addition of the ptc1 ligand, sonic
      hedgehog (shh), disrupts this interaction and allows cyclin B1 to localize to the
      nucleus. Expression of ptc1 in 293T cells was inhibitory to cell proliferation;
      this inhibition could be relieved by coexpression of a cyclin B1 derivative that
      constitutively localizes to the nucleus and that could not interact with ptc1 due
      to phosphorylation-site mutations to ALA: In addition, we demonstrate that
      endogenous ptc1 and endogenous cyclin B1 interact in vivo. The findings reported
      here demonstrate that ptc1 participates in determining the subcellular
      localization of cyclin B1 and suggest a link between the tumor suppressor
      activity of ptc1 and the regulation of cell division. Thus, we propose that ptc1
      participates in a G(2)/M checkpoint by regulating the localization of MPF.

PMID- 11331588
TI  - Transitions in histone acetylation reveal boundaries of three separately
      regulated neighboring loci.
AB  - We have studied developmentally regulated patterns of histone acetylation at high
      resolution across approximately 54 kb of DNA containing three independently
      regulated but neighboring genetic loci. These include a folate receptor gene, a
      16 kb condensed chromatin region, the chicken beta-globin domain and an adjacent
      olfactory receptor gene. Within these regions the relative levels of acetylation
      appear to fall into three classes. The condensed chromatin region maintains the
      lowest acetylation at every developmental stage. Genes that are inactive show
      similarly low levels, but activation results in a dramatic increase in
      acetylation. The highest levels of acetylation are seen at regulatory sites
      upstream of the genes. These patterns imply the action of more than one class of
      acetylation. Notably, there is a very strong constitutive focus of
      hyperacetylation at the 5' insulator element separating the globin locus from the
      folate receptor region, which suggests that this insulator element may harbor a
      high concentration of histone acetylases.

PMID- 11331589
TI  - Association and spreading of the Drosophila dosage compensation complex from a
      discrete roX1 chromatin entry site.
AB  - In Drosophila, dosage compensation is controlled by the male-specific lethal
      (MSL) complex consisting of MSL proteins and roX RNAs. The MSL complex is
      specifically localized on the male X chromosome to increase its expression
      approximately 2-fold. We recently proposed a model for the targeted assembly of
      the MSL complex, in which initial binding occurs at approximately 35 dispersed
      chromatin entry sites, followed by spreading in cis into flanking regions. Here,
      we analyze one of the chromatin entry sites, the roX1 gene, to determine which
      sequences are sufficient to recruit the MSL complex. We found association and
      spreading of the MSL complex from roX1 transgenes in the absence of detectable
      roX1 RNA synthesis from the transgene. We mapped the recruitment activity to a
      217 bp roX1 fragment that shows male-specific DNase hypersensitivity and can be
      preferentially cross-linked in vivo to the MSL complex. When inserted on
      autosomes, this small roX1 segment is sufficient to produce an ectopic chromatin
      entry site that can nucleate binding and spreading of the MSL complex hundreds of
      kilobases into neighboring regions.

PMID- 11331590
TI  - Local action of long-range repressors in the Drosophila embryo.
AB  - Previous studies have identified two corepressors in the early Drosophila embryo:
      Groucho and dCTBP: Both proteins are recruited to the DNA template by interacting
      with short peptide motifs conserved in a variety of sequence-specific
      transcriptional repressors. Once bound to DNA, Groucho appears to mediate long
      range repression, while dCtBP directs short-range repression. The short-range
      Kruppel repressor was converted into a long-range repressor by replacing the
      dCtBP interaction motif (PxDLSxH) with a Groucho motif (WRPW). The resulting
      chimeric repressor causes a different mutant phenotype from that of the native
      Kruppel protein when misexpressed in transgenic embryos. The different patterning
      activities can be explained on the basis of long-range silencing within the hairy
      5' regulatory region. The analysis of a variety of synthetic transgenes provides
      evidence that Groucho-dependent long-range repressors do not always cause the
      dominant silencing of linked enhancers within a complex cis-regulatory region. We
      suggest a "hot chromatin" model, whereby repressors require activators to bind
      DNA.

PMID- 11331591
TI  - TGF-beta-induced repression of CBFA1 by Smad3 decreases cbfa1 and osteocalcin
      expression and inhibits osteoblast differentiation.
AB  - Transforming growth factor-beta (TGF-beta), a secreted factor present at high
      levels in bone, inhibits osteoblast differentiation in culture; yet, the
      mechanism of this inhibition remains unclear. We studied the effects of TGF-beta
      and its effectors, the Smads, on the expression and function of the osteoblast
      transcription factor CBFA1. TGF-beta inhibited the expression of the cbfa1 and
      osteocalcin genes, whose expression is controlled by CBFA1 in osteoblast-like
      cell lines. This inhibition was mediated by Smad3, which interacts physically
      with CBFA1 and represses its transcriptional activity at the CBFA1-binding OSE2
      promoter sequence. The repression of CBFA1 function by Smad3 contrasts with
      previous observations that Smads function as transcription activators. This
      repression occurred in mesenchymal but not epithelial cells, and depended on the
      promoter sequence. Smad3-mediated repression of CBFA1 provides a central
      regulatory mechanism for the inhibition of osteoblast differentiation by TGF
      beta, since it inhibits both cbfa1 transcription and transcriptional activation
      of osteoblast differentiation genes by CBFA1. Altering Smad3 signaling influenced
      osteoblast differentiation in the presence or absence of TGF-beta, implicating
      Smad3/TGF-beta-mediated repression in autocrine regulation of osteoblast
      differentiation.

PMID- 11331592
TI  - TRIP-Br: a novel family of PHD zinc finger- and bromodomain-interacting proteins
      that regulate the transcriptional activity of E2F-1/DP-1.
AB  - We report the isolation of TRIP-Br1, a transcriptional regulator that interacts
      with the PHD-bromodomain of co-repressors of Kruppel-associated box (KRAB)
      mediated repression, KRIP-1(TIF1beta) and TIF1alpha, as well as the co
      activator/adaptor p300/CBP. TRIP-Br1 and the related protein TRIP-Br2 possess
      transactivation domains. Like MDM2, which has a homologous transactivation
      domain, TRIP-Br proteins functionally contact DP-1, stimulating E2F-1/DP-1
      transcriptional activity. KRIP-1 potentiates TRIP-Br protein co-activation of E2F
      1/DP-1. TRIP-Br1 is a component of a multiprotein complex containing E2F-1 and DP
      1. Co-expression of the retinoblastoma gene product (RB) abolishes baseline E2F
      1/DP-1 transcriptional activity as well as TRIP-Br/KRIP-1 co-activation, both of
      which are restored by the adenovirus E1A oncoprotein. These features suggest that
      TRIP-Br proteins function at E2F-responsive promoters to integrate signals
      provided by PHD- and/or bromodomain- containing transcription factors. TRIP-Br1
      is identical to the cyclin-dependent kinase 4 (cdk4)-binding protein p34(SEI-1),
      which renders the activity of cyclin D/cdk4 resistant to the inhibitory effect of
      p16(INK4a) during late G(1). TRIP-Br1(p34(SEI-1)) is differentially overexpressed
      during the G(1) and S phases of the cell cycle, consistent with a dual role for
      TRIP-Br1(p34(SEI-1)) in the regulation of cell cycle progression through
      sequential effects on the transcriptional activity of E2F-responsive promoters
      during G(1) and S phases.

PMID- 11331593
TI  - Interleukin 3-dependent activation of DREAM is involved in transcriptional
      silencing of the apoptotic Hrk gene in hematopoietic progenitor cells.
AB  - The apoptotic protein Hrk is expressed in hematopoietic progenitors after growth
      factor deprivation. Here we identify a silencer sequence in the 3' untranslated
      region of the hrk gene that binds to the transcriptional repressor DREAM in
      interleukin-3 (IL-3)-dependent hematopoietic progenitor cells, and abrogates the
      expression of reporter genes when located downstream of the open reading frame.
      In addition, the binding of DREAM to the hrk gene is reduced or eliminated when
      cells are cultured in the absence of IL-3 or treated with a calcium ionophore or
      a phosphatidylinositol 3-kinase-specific inhibitor, suggesting that both calcium
      mobilization and phosphorylation can regulate the transcriptional activity of
      DREAM. Furthermore, we have shown that DREAM is phosphorylated by a
      phosphatidylinositol 3-kinase-dependent, but Akt-independent pathway. In all
      cases, loss of the DREAM-DNA binding complex was correlated with increased levels
      of Hrk and apoptosis. These data suggest that IL-3 may trigger the activation of
      DREAM through different signaling pathways, which in turn binds to a silencer
      sequence in the hrk gene and blocks transcription, avoiding inappropriate cell
      death in hematopoietic progenitors.

PMID- 11331594
TI  - RNA binding in an Sm core domain: X-ray structure and functional analysis of an
      archaeal Sm protein complex.
AB  - Eukaryotic Sm and Sm-like proteins associate with RNA to form the core domain of
      ribonucleoprotein particles involved in pre-mRNA splicing and other processes.
      Recently, putative Sm proteins of unknown function have been identified in
      Archaea. We show by immunoprecipitation experiments that the two Sm proteins
      present in Archaeoglobus fulgidus (AF-Sm1 and AF-Sm2) associate with RNase P RNA
      in vivo, suggesting a role in tRNA processing. The AF-Sm1 protein also interacts
      specifically with oligouridylate in vitro. We have solved the crystal structures
      of this protein and a complex with RNA. AF-Sm1 forms a seven-membered ring, with
      the RNA interacting inside the central cavity on one face of the doughnut-shaped
      complex. The bases are bound via stacking and specific hydrogen bonding contacts
      in pockets lined by residues highly conserved in archaeal and eukaryotic Sm
      proteins, while the phosphates remain solvent accessible. A comparison with the
      structures of human Sm protein dimers reveals closely related monomer folds and
      intersubunit contacts, indicating that the architecture of the Sm core domain and
      RNA binding have been conserved during evolution.

PMID- 11331595
TI  - SMNrp is an essential pre-mRNA splicing factor required for the formation of the
      mature spliceosome.
AB  - SMNrp, also termed SPF30, has recently been identified in spliceosomes assembled
      in vitro. We have functionally characterized this protein and show that it is an
      essential splicing factor. We show that SMNrp is a 17S U2 snRNP-associated
      protein that appears in the pre-spliceosome (complex A) and the mature
      spliceosome (complex B) during splicing. Immunodepletion of SMNrp from nuclear
      extract inhibits the first step of pre-mRNA splicing by preventing the formation
      of complex B. Re-addition of recombinant SMNrp to immunodepleted extract
      reconstitutes both spliceosome formation and splicing. Mutations in two domains
      of SMNrp, although similarly deleterious for splicing, differed in their
      consequences on U2 snRNP binding, suggesting that SMNrp may also engage in
      interactions with splicing factors other than the U2 snRNP. In agreement with
      this, we present evidence for an additional interaction between SMNrp and the
      [U4/U6.U5] tri-snRNP. A candidate that may mediate this interaction, namely the
      U4/U6-90 kDa protein, has been identified. We suggest that SMNrp, as a U2 snRNP
      associated protein, facilitates the recruitment of the [U4/U6.U5] tri-snRNP to
      the pre-spliceosome.

PMID- 11331596
TI  - A proline-rich protein binds to the localization element of Xenopus Vg1 mRNA and
      to ligands involved in actin polymerization.
AB  - A 340 nucleotide element within the 3' untranslated region of Vg1 mRNA determines
      its localization to the vegetal cortex of Xenopus oocytes. To identify protein
      factors that bind to this region, we screened a cDNA expression library with an
      RNA probe containing this sequence. Five independent isolates encoded a protein
      (designated Prrp for proline-rich RNA binding protein) having two RNP domains
      followed by multiple polyproline segments. Prrp and Vg1 mRNAs are co-localized to
      the vegetal cortex of stage IV oocytes, substantiating an interaction between the
      two in vivo. Prrp also associates with VegT mRNA, which like Vg1 mRNA uses the
      late localization pathway, but not with Xcat-2 or Xwnt-11 mRNAs, which use the
      early pathway. The proline-rich domain of Prrp interacts with profilin, a protein
      that promotes actin polymerization. Prrp can also associate with the EVH1 domain
      of Mena, another microfilament-associated protein. Since the anchoring of Vg1
      mRNA to the vegetal cortex is actin dependent, one function of Prrp may be to
      facilitate local actin polymerization, representing a novel function for an RNA
      binding protein.

PMID- 11331597
TI  - Multiple roles for the C-terminal domain of eIF5 in translation initiation
      complex assembly and GTPase activation.
AB  - eIF5 stimulates the GTPase activity of eIF2 bound to Met-tRNA(i)(Met), and its C
      terminal domain (eIF5-CTD) bridges interaction between eIF2 and eIF3/eIF1 in a
      multifactor complex containing Met-tRNA(i)(Met). The tif5-7A mutation in eIF5
      CTD, which destabilizes the multifactor complex in vivo, reduced the binding of
      Met-tRNA(i)(Met) and mRNA to 40S subunits in vitro. Interestingly, eIF5-CTD bound
      simultaneously to the eIF4G subunit of the cap-binding complex and the NIP1
      subunit of eIF3. These interactions may enhance association of eIF4G with eIF3 to
      promote mRNA binding to the ribosome. In vivo, tif5-7A eliminated eIF5 as a
      stable component of the pre-initiation complex and led to accumulation of 48S
      complexes containing eIF2; thus, conversion of 48S to 80S complexes is the rate
      limiting defect in this mutant. We propose that eIF5-CTD stimulates binding of
      Met-tRNA(i)(Met) and mRNA to 40S subunits through interactions with eIF2, eIF3
      and eIF4G; however, its most important function is to anchor eIF5 to other
      components of the 48S complex in a manner required to couple GTP hydrolysis to
      AUG recognition during the scanning phase of initiation.

PMID- 11331598
TI  - SRbeta coordinates signal sequence release from SRP with ribosome binding to the
      translocon.
AB  - Protein targeting to the endoplasmic reticulum (ER) membrane is regulated by
      three GTPases, the 54 kDa subunit of the signal recognition particle (SRP) and
      the alpha- and beta-subunits of the SRP receptor (SR). Using a soluble form of SR
      and an XTP-binding mutant of SRbeta, we show that SRbeta is essential for protein
      translocation across the ER membrane. SRbeta can be cross-linked to a 21 kDa
      ribosomal protein in its empty and GDP-bound state, but not when GTP is bound.
      GTP binding to SRbeta is required to induce signal sequence release from SRP.
      This is achieved by the presence of the translocon, which changes the interaction
      between the 21 kDa ribosomal protein and SRbeta and thereby allows SRbeta to bind
      GTP. We conclude that SRbeta coordinates the release of the signal sequence from
      SRP with the presence of the translocon.

PMID- 11331599
TI  - Transcriptional activation: risky business.
AB  - Transcriptional regulation is all about getting RNA polymerase to the right place
      on the gene at the right time and making sure that it is competent to conduct
      transcription. Traditional views of this process place most of their emphasis on
      the events that precede initiation of transcription. We imagine a promoter-bound
      transcriptional activator (or collection of activators) recruiting components of
      the basal transcriptional machinery to the DNA, eventually leading to the
      recruitment of RNA polymerase II and the onset of gene transcription. Although
      these events play a crucial role in regulating gene expression, they are only
      half the story. Correct regulation of transcription requires that polymerase not
      only initiates when and where it should, but that it stops initiating when no
      longer appropriate. But how are the signals from transcriptional activators,
      telling RNA polymerase to fire, terminated? Is this process governed by chance,
      with activators simply falling off the promoter at a certain frequency? Or is
      there some more direct mechanism, whereby activators are aggressively limited
      from uncontrolled promoter activation? A new article by suggests the latter may
      be true, and provides a mechanism for how a component of the basal transcription
      machinery can mark the activators it has encountered, sentencing them to an early
      death or banishing them from the nucleus. The ability of the basal
      transcriptional apparatus to mark activators provides an efficient way to limit
      activator function and ensures that continuing transcription initiation at a
      promoter is coupled to the continuing synthesis and activation of transcriptional
      activators.

PMID- 11331600
TI  - Linking nutritional status to gene activation and development.

PMID- 11331601
TI  - RAD51-independent break-induced replication to repair a broken chromosome depends
      on a distant enhancer site.
AB  - Without the RAD51 strand exchange protein, Saccharomyces cerevisiae cannot repair
      a double-strand break (DSB) by gene conversion. However, cells can repair DSBs by
      recombination-dependent, break-induced replication (BIR). RAD51-independent BIR
      is initiated more than 13 kb from the DSB. Repair depends on a 200-bp sequence
      adjacent to ARS310, located approximately 34 kb centromere-proximal to the DSB,
      but does not depend on the origin activity of ARS310. We conclude that the
      ability of a recombination-induced replication fork to copy > 130 kb to the end
      of the chromosome depends on a special site that enhances assembly of a
      processive repair replication fork.

PMID- 11331602
TI  - Asf1 links Rad53 to control of chromatin assembly.
AB  - Yeast defective in the checkpoint kinase Rad53 fail to recover from transient DNA
      replication blocks and synthesize intact chromosomes. The effectors of Rad53
      relevant to this recovery process are unknown. Here we report that overproduction
      of the chromatin assembly factor Asf1 can suppress the Ts phenotype of mrc1rad53
      double mutants and the HU sensitivity of rad53 mutants. Eliminating silencing
      also suppresses this lethality, further implicating chromatin structure in
      checkpoint function. We find that Asf1 and Rad53 exist in a dynamic complex that
      dissociates in response to replication blocks and DNA damage. Thus, checkpoint
      pathways directly regulate chromatin assembly to promote survival in response to
      DNA damage and replication blocks.

PMID- 11331603
TI  - ATM-dependent phosphorylation of Mdm2 on serine 395: role in p53 activation by
      DNA damage.
AB  - The p53 tumor suppressor protein, a key regulator of cellular responses to
      genotoxic stress, is stabilized and activated after DNA damage. The rapid
      activation of p53 by ionizing radiation and radiomimetic agents is largely
      dependent on the ATM kinase. p53 is phosphorylated by ATM shortly after DNA
      damage, resulting in enhanced stability and activity of p53. The Mdm2 oncoprotein
      is a pivotal negative regulator of p53. In response to ionizing radiation and
      radiomimetic drugs, Mdm2 undergoes rapid ATM-dependent phosphorylation prior to
      p53 accumulation. This results in a decrease in its reactivity with the 2A10
      monoclonal antibody. Phage display analysis identified a consensus 2A10
      recognition sequence, possessing the core motif DYS. Unexpectedly, this motif
      appears twice within the human Mdm2 molecule, at positions corresponding to
      residues 258-260 and 393-395. Both putative 2A10 epitopes are highly conserved
      and encompass potential phosphorylation sites. Serine 395, residing within the
      carboxy-terminal 2A10 epitope, is the major target on Mdm2 for phosphorylation by
      ATM in vitro. Mutational analysis supports the conclusion that Mdm2 undergoes ATM
      dependent phosphorylation on serine 395 in vivo in response to DNA damage. The
      data further suggests that phosphorylated Mdm2 may be less capable of promoting
      the nucleo-cytoplasmic shuttling of p53 and its subsequent degradation, thereby
      enabling p53 accumulation. Our findings imply that activation of p53 by DNA
      damage is achieved, in part, through attenuation of the p53-inhibitory potential
      of Mdm2.

PMID- 11331604
TI  - Negative regulation of Gcn4 and Msn2 transcription factors by Srb10 cyclin
      dependent kinase.
AB  - The budding yeast transcriptional activator Gcn4 is rapidly degraded in an
      SCF(Cdc4)-dependent manner in vivo. Upon fractionation of yeast extracts to
      identify factors that mediate Gcn4 ubiquitination, we found that Srb10
      phosphorylates Gcn4 and thereby marks it for recognition by SCF(Cdc4) ubiquitin
      ligase. Srb10 is a physiological regulator of Gcn4 stability because both
      phosphorylation and turnover of Gcn4 are diminished in srb10 mutants. Gcn4 is
      almost completely stabilized in srb10Delta pho85Delta cells, or upon mutation of
      all Srb10 phosphorylation sites within Gcn4, suggesting that the Pho85 and Srb10
      cyclin-dependent kinases (CDKs) conspire to limit the accumulation of Gcn4. The
      multistress response transcriptional regulator Msn2 is also a substrate for Srb10
      and is hyperphosphorylated in an Srb10-dependent manner upon heat-stress-induced
      translocation into the nucleus. Whereas Msn2 is cytoplasmic in resting wild-type
      cells, its nuclear exclusion is partially compromised in srb10 mutant cells.
      Srb10 has been shown to repress a subset of genes in vivo, and has been proposed
      to inhibit transcription via phosphorylation of the C-terminal domain of RNA
      polymerase II. We propose that Srb10 also inhibits gene expression by promoting
      the rapid degradation or nuclear export of specific transcription factors.
      Simultaneous down-regulation of both transcriptional regulatory proteins and RNA
      polymerase may enhance the potency and specificity of transcriptional inhibition
      by Srb10.

PMID- 11331605
TI  - Bacillus subtilis CodY represses early-stationary-phase genes by sensing GTP
      levels.
AB  - CodY, a highly conserved protein in the low G + C, gram-positive bacteria,
      regulates the expression of many Bacillus subtilis genes that are induced as
      cells make the transition from rapid exponential growth to stationary phase and
      sporulation. This transition has been associated with a transient drop in the
      intracellular pool of GTP. Many stationary-phase genes are also induced during
      exponential-growth phase by treatment of cells with decoyinine, a GMP synthetase
      inhibitor. The effect of decoyinine on an early-stationary-phase gene is shown
      here to be mediated through CodY and to reflect a reduction in guanine nucleotide
      accumulation. CodY proved to bind GTP in vitro. Moreover, CodY-mediated
      repression of target promoters was dependent on a high concentration of GTP,
      comparable to that found in rapidly growing exponential-phase cells. Because a
      codY-null mutant was able to sporulate under conditions of nutrient excess, CodY
      also appears to be a critical factor that normally prevents sporulation under
      such conditions. Thus, B. subtilis CodY is a novel GTP-binding protein that
      senses the intracellular GTP concentration as an indicator of nutritional
      conditions and regulates the transcription of early-stationary-phase and
      sporulation genes, allowing the cell to adapt to nutrient limitation.

PMID- 11331606
TI  - Subcellular localization of the Snf1 kinase is regulated by specific beta
      subunits and a novel glucose signaling mechanism.
AB  - The Snf1/AMP-activated protein kinase family has broad roles in transcriptional,
      metabolic, and developmental regulation in response to stress. In Saccharomyces
      cerevisiae, Snf1 is required for the response to glucose limitation. Snf1 kinase
      complexes contain the alpha (catalytic) subunit Snf1, one of the three related
      beta subunits Gal83, Sip1, or Sip2, and the gamma subunit Snf4. We present
      evidence that the beta subunits regulate the subcellular localization of the Snf1
      kinase. Green fluorescent protein fusions to Gal83, Sip1, and Sip2 show different
      patterns of localization to the nucleus, vacuole, and/or cytoplasm. We show that
      Gal83 directs Snf1 to the nucleus in a glucose-regulated manner. We further
      identify a novel signaling pathway that controls this nuclear localization in
      response to glucose phosphorylation. This pathway is distinct from the glucose
      signaling pathway that inhibits Snf1 kinase activity and responds not only to
      glucose but also to galactose and sucrose. Such independent regulation of the
      localization and the activity of the Snf1 kinase, combined with the distinct
      localization of kinases containing different beta subunits, affords versatility
      in regulating physiological responses.

PMID- 11331607
TI  - COBRA encodes a putative GPI-anchored protein, which is polarly localized and
      necessary for oriented cell expansion in Arabidopsis.
AB  - To control organ shape, plant cells expand differentially. The organization of
      the cellulose microfibrils in the cell wall is a key determinant of differential
      expansion. Mutations in the COBRA (COB) gene of Arabidopsis, known to affect the
      orientation of cell expansion in the root, are reported here to reduce the amount
      of crystalline cellulose in cell walls in the root growth zone. The COB gene,
      identified by map-based cloning, contains a sequence motif found in proteins that
      are anchored to the extracellular surface of the plasma membrane through a
      glycosylphosphatidylinositol (GPI) linkage. In animal cells, this lipid linkage
      is known to confer polar localization to proteins. The COB protein was detected
      predominately on the longitudinal sides of root cells in the zone of rapid
      elongation. Moreover, COB RNA levels are dramatically upregulated in cells
      entering the zone of rapid elongation. Based on these results, models are
      proposed for the role of COB as a regulator of oriented cell expansion.

PMID- 11331608
TI  - The chimeric leucine-rich repeat/extensin cell wall protein LRX1 is required for
      root hair morphogenesis in Arabidopsis thaliana.
AB  - In plants, the cell wall is a major determinant of cell morphogenesis. Cell
      enlargement depends on the tightly regulated expansion of the wall, which
      surrounds each cell. However, the qualitative and quantitative mechanisms
      controlling cell wall enlargement are still poorly understood. Here, we report
      the molecular and functional characterization of LRX1, a new Arabidopsis gene
      that encodes a chimeric leucine-rich repeat/extensin protein. LRX1 is expressed
      in root hair cells and the protein is specifically localized in the wall of the
      hair proper, where it becomes insolubilized during development. lrx1-null
      mutants, isolated by a reverse-genetic approach, develop root hairs that
      frequently abort, swell, or branch. Complementation and overexpression
      experiments using modified LRX1 proteins indicate that the interaction with the
      cell wall is important for LRX1 function. These results suggest that LRX1 is an
      extracellular component of a mechanism regulating root hair morphogenesis and
      elongation by controlling either polarized growth or cell wall formation and
      assembly.

PMID- 11331609
TI  - Sharp, an inducible cofactor that integrates nuclear receptor repression and
      activation.
AB  - A yeast two-hybrid screen using the conserved carboxyl terminus of the nuclear
      receptor corepressor SMRT as a bait led to the isolation of a novel human gene
      termed SHARP (SMRT/HDAC1 Associated Repressor Protein). SHARP is a potent
      transcriptional repressor whose repression domain (RD) interacts directly with
      SMRT and at least five members of the NuRD complex including HDAC1 and HDAC2. In
      addition, SHARP binds to the steroid receptor RNA coactivator SRA via an
      intrinsic RNA binding domain and suppresses SRA-potentiated steroid receptor
      transcription activity. Accordingly, SHARP has the capacity to modulate both
      liganded and nonliganded nuclear receptors. Surprisingly, the expression of SHARP
      is itself steroid inducible, suggesting a simple feedback mechanism for
      attenuation of the hormonal response.

PMID- 11331610
TI  - Xenopus Sprouty2 inhibits FGF-mediated gastrulation movements but does not affect
      mesoderm induction and patterning.
AB  - Signal transduction through the FGF receptor is essential for the specification
      of the vertebrate body plan. Blocking the FGF pathway in early Xenopus embryos
      inhibits mesoderm induction and results in truncation of the anterior-posterior
      axis. The Drosophila gene sprouty encodes an antagonist of FGF signaling, which
      is transcriptionally induced by the pathway, but whose molecular functions are
      poorly characterized. We have cloned Xenopus sprouty2 and show that it is
      expressed in a similar pattern to known FGFs and is dependent on the FGF/Ras/MAPK
      pathway for its expression. Overexpression of Xsprouty2 in both embryos and
      explant assays results in the inhibition of the cell movements of convergent
      extension. Although blocking FGF/Ras/MAPK signaling leads to an inhibition of
      mesodermal gene expression, these markers are unaffected by Xsprouty2, indicating
      that mesoderm induction and patterning occurs normally in these embryos. Finally,
      using Xenopus oocytes we show that Xsprouty2 is an intracellular antagonist of
      FGF-dependent calcium signaling. These results provide evidence for at least two
      distinct FGF-dependent signal transduction pathways: a Sprouty-insensitive
      Ras/MAPK pathway required for the transcription of most mesodermal genes, and a
      Sprouty-sensitive pathway required for coordination of cellular morphogenesis.

PMID- 11331611
TI  - Induced myelination and demyelination in a conditional mouse model of Charcot
      Marie-Tooth disease type 1A.
AB  - Charcot-Marie-Tooth disease type 1A, a hereditary demyelinating neuropathy, is
      usually caused by overexpression of peripheral myelin protein 22 (PMP22) due to a
      genomic duplication. We have generated a transgenic mouse model in which mouse
      pmp22 overexpression can be regulated. In this mouse model, overexpression of
      pmp22 occurs specifically in Schwann cells of the peripheral nerve and is
      switched off when the mice are fed tetracycline. Overexpression of pmp22
      throughout life (in the absence of tetracycline) causes demyelination. In
      contrast, myelination is nearly normal when pmp22 overexpression is switched off
      throughout life by feeding the mice tetracycline. When overexpression of pmp22 is
      switched off in adult mice, correction begins within 1 week and myelination is
      well advanced by 3 months (although the myelin sheaths are still thinner than
      normal), indicating that the Schwann cells are poised to start myelination.
      Upregulation of the gene in adult mice (which had previously had normal pmp22
      expression) is followed by active demyelination within 1 week, which had
      plateaued by 8 weeks. This indicates that Schwann cells with mature myelin are
      sensitive to increased amounts of pmp22 such that they rapidly demyelinate. Thus,
      demyelination can largely be corrected within a few months, but the correction
      will be sensitive to subsequent upregulation of pmp22.

PMID- 11331612
TI  - von Hippel-Lindau protein mutants linked to type 2C VHL disease preserve the
      ability to downregulate HIF.
AB  - von Hippel-Lindau (VHL) disease is a hereditary cancer syndrome caused by germ
      line mutation of the von Hippel-Lindau tumor suppressor gene (VHL). Tumors
      observed in this disorder include retinal and central nervous system
      hemangioblastomas, clear cell renal carcinomas and pheochromocytomas. The VHL
      gene product, pVHL, is a component of a ubiquitin ligase which targets the
      transcription factor known as hypoxia-inducible factor (HIF) for degradation in
      the presence of oxygen. pVHL also plays roles in the control of extracellular
      matrix formation and cell-cycle exit. Different VHL mutations confer different
      site-specific risks of cancer. Type 2C VHL mutations confer an increased risk of
      pheochromocytoma without the other stigmata of VHL disease. Here we report that
      the products of such type 2C VHL alleles retain the ability to down regulate HIF
      but are defective for promotion of fibronectin matrix assembly. Furthermore, pVHL
      L188V, a well studied type 2C mutant, retained the ability to suppress renal
      carcinoma growth in vivo. These studies strengthen the notion that HIF
      deregulation plays a causal role in hemangioblastoma and renal carcinoma, and
      raises the possibility that abnormal fibronectin matrix assembly contributes to
      pheochromocytoma pathogenesis in the setting of VHL disease.

PMID- 11331613
TI  - Contrasting effects on HIF-1alpha regulation by disease-causing pVHL mutations
      correlate with patterns of tumourigenesis in von Hippel-Lindau disease.
AB  - The von Hippel-Lindau tumour suppressor gene product (pVHL) associates with the
      elongin B and C and Cul2 proteins to form a ubiquitin-ligase complex (VCBC). To
      date, the only VCBC substrates identified are the hypoxia-inducible factor alpha
      subunits (HIF-1alpha and HIF-2alpha). However, pVHL is thought to have multiple
      functions and the significance of HIF-1alpha and HIF-2alpha regulation for tumour
      suppressor activity has not been defined. VHL disease is characterized by
      distinct clinical subtypes. Thus haemangioblastomas (HABs) and renal cell
      carcinoma (RCC) but not phaeochromocytoma (PHE) occur in type 1 VHL disease. Type
      2 subtypes are characterized by PHE susceptibility but differ with respect to
      additional tumours (type 2A, PHE+HAB but not RCC; type 2B, PHE+ HAB+RCC; type 2C,
      PHE only). We investigated in detail the effect of 13 naturally occurring VHL
      mutations (11 missense), representing each phenotypic subclass, on HIF-alpha
      subunit regulation. Consistent effects on pVHL function were observed for all
      mutations within each subclass. Mutations associated with the PHE-only phenotype
      (type 2C) promoted HIF-alpha ubiquitylation in vitro and demonstrated wild-type
      binding patterns with pVHL interacting proteins, suggesting that loss of other
      pVHL functions are necessary for PHE susceptibility. Mutations causing HAB
      susceptibility (types 1, 2A and 2B) demonstrated variable effects on HIF-alpha
      subunit and elongin binding, but all resulted in defective HIF-alpha regulation
      and loss of p220 (fibronectin) binding. All RCC-associated mutations caused
      complete HIF-alpha dysregulation and loss of p220 (fibronectin) binding. Our
      findings are consistent with impaired ability to degrade HIF-alpha subunit being
      required for HAB development and RCC susceptibility.

PMID- 11331614
TI  - Transgenic mice with an expanded CAG repeat controlled by the human AR promoter
      show polyglutamine nuclear inclusions and neuronal dysfunction without neuronal
      cell death.
AB  - We generated transgenic mice that expressed a highly expanded 239 polyglutamine
      (polyQ) repeat under the control of the human androgen receptor promoter. These
      transgenic mice developed progressive neurological phenotypes of muscular
      weakness and ataxia, small body size and short life-span. PolyQ nuclear
      inclusions (NIs) were remarkable and widespread but found in selective regions of
      the central nervous system (CNS) such as the spinal cord, cerebrum and cerebellum
      as well as in selective peripheral visceral organs. This distribution pattern
      resembled that of spinal and bulbar muscular atrophy somewhat, but was more
      widespread. In neuronal tissues, NIs were present in astrocytes as well as
      neurons. Cytoplasmic and axonal inclusions were not observed. In the CNS regions
      with abundant NIs, neuronal populations were well-preserved, and neither neuronal
      cell death, reactive astrogliosis nor microglial invasions were detected. These
      findings suggest that polyQ alone can induce the neuronal dysfunction that
      precedes gross neuronal degeneration and provides a clue for investigating
      molecular mechanisms that underly the pathway to neuronal dysfunction from polyQ
      expansion.

PMID- 11331615
TI  - Altered proteasomal function due to the expression of polyglutamine-expanded
      truncated N-terminal huntingtin induces apoptosis by caspase activation through
      mitochondrial cytochrome c release.
AB  - Expansion of CAG repeats within the coding region of target genes is the cause of
      several autosomal dominant neurodegenerative diseases including Huntington's
      disease (HD). A hallmark of HD is the proteolytic production of N-terminal
      fragments of huntingtin containing polyglutamine repeats that form ubiquitinated
      aggregates in the nucleus and cytoplasm of the affected neurons. In this study,
      we used an ecdysone-inducible stable mouse neuro2a cell line that expresses
      truncated N-terminal huntingtin (tNhtt) with different polyglutamine length,
      along with mice transgenic for HD exon 1, to demonstrate that the ubiquitin
      proteasome pathway is involved in the pathogenesis of HD. Proteasomal 20S core
      catalytic component was redistributed to the polyglutamine aggregates in both the
      cellular and transgenic mouse models. Proteasome inhibitor dramatically increased
      the rate of aggregate formation caused by tNhtt protein with 60 glutamine (60Q)
      repeats, but had very little influence on aggregate formation by tNhtt protein
      with 150Q repeats. Both normal and polyglutamine-expanded tNhtt proteins were
      degraded by proteasome, but the rate of degradation was inversely proportional to
      the repeat length. The shift of the proteasomal components from the total
      cellular environment to the aggregates, as well as the comparatively slower
      degradation of tNhtt with longer polyglutamine, decreased the proteasome's
      availability for degrading other key target proteins, such as p53. This altered
      proteasomal function was associated with disrupted mitochondrial membrane
      potential, released cytochrome c from mitochondria into the cytosol and activated
      caspase-9- and caspase-3-like proteases. These results suggest that the impaired
      proteasomal function plays an important role in polyglutamine protein-induced
      cell death.

PMID- 11331616
TI  - DCX in PC12 cells: CREB-mediated transcription and neurite outgrowth.
AB  - Mutations in doublecortin (DCX) result in X-linked lissencephaly in males. To
      explore the role of DCX in differentiation and signal transduction we
      overexpressed DCX in PC12 cells. Our results indicate that DCX stabilizes
      microtubules and inhibits neurite outgrowth in nerve growth factor-induced
      differentiation. However, neurite length is increased when differentiation is
      induced by epidermal growth factor and forskolin or by dibutyryl-cAMP.
      Furthermore, CREB-mediated transcription is downregulated, supporting the notion
      that cytoskeletal regulatory proteins can affect the transcriptional state of a
      cell. Using different constructs and mutations we reach the conclusion that
      microtubule stabilization is a key factor, but not the only one, in controlling
      neurite extension. Overexpression of a mutation found in a lissencephaly patient
      (S47R), completely blocks neurite outgrowth. We propose that these functions are
      important during normal and abnormal brain development.

PMID- 11331617
TI  - Defect of histone acetyltransferase activity of the nuclear transcriptional
      coactivator CBP in Rubinstein-Taybi syndrome.
AB  - CREB-binding protein (CBP) is a transcriptional coactivator that has intrinsic
      histone acetyltransferase (HAT) activity. CBP is the causative gene of Rubinstein
      Taybi syndrome (RTS). To investigate the relationships between CBP HAT activity
      and RTS, we analyzed 16 RTS patients. A microdeletion was identified in one
      patient by fluorescent in situ hybridization analysis. Heteroallelic mutations
      were identified in five patients by reverse transcriptase-polymerase chain
      reaction-single-strand conformation polymorphism analysis and sequencing. These
      included a 2 bp deletion between nucleotides 4319 and 4320, an 11 bp deletion
      between nucleotides 4898 and 4908, a 14 bp insertion (CCTCGGTCCTGCAC) between
      nucleotides 5212 and 5213, a 2 bp deletion between nucleotides 5222 and 5223, and
      a missense mutation from guanine (G) to cytosine (C) at nucleotide 4951 that
      changed codon 1378 from CGG (arginine) to CCG (proline). The identical missense
      mutation was introduced into the recombinant mouse CBP. It abolished the HAT
      activity of CBP and the ability of CBP to transactivate cyclic AMP-response
      element binding protein (CREB), in HAT assays and in microinjection experiments,
      respectively. These results suggest that the loss of the HAT activity of CBP may
      cause RTS, as the first example of a defect of HAT activity in a human disease.
      Our findings raise the possibility that treatment of RTS patients with histone
      deacetylase inhibitors might have beneficial effects.

PMID- 11331618
TI  - Trans-ethnic fine mapping of a quantitative trait locus for circulating
      angiotensin I-converting enzyme (ACE).
AB  - Circulating angiotensin I-converting enzyme (ACE) levels are influenced by a
      major quantitative trait locus (QTL) that maps to the ACE gene. Phylogenetic and
      measured haplotype analyses have suggested that the ACE-linked QTL lies
      downstream of a putative ancestral breakpoint located near to position 6435.
      However, strong linkage disequilibrium between markers in the 3' portion of the
      gene has prevented further resolution of the QTL in Caucasian subjects. We have
      examined 10 ACE gene polymorphisms in Afro-Caribbean families recruited in
      JAMAICA: Variance components analyses showed strong evidence of linkage and
      association to circulating ACE levels. When the linkage results were contrasted
      with those from a set of British Caucasian families, there was no evidence for
      heterogeneity between the samples. However, patterns of allelic association
      between the markers and circulating ACE levels differed significantly in the two
      data sets. In the British families, three markers [G2215A, Alu insertion/deletion
      and G2350A] were in complete disequilibrium with the ACE-linked QTL. In the
      Jamaican families, only marker G2350A showed strong but incomplete disequilibrium
      with the ACE-linked QTL. These results suggest that additional unobserved
      polymorphisms have an effect on circulating ACE levels in Jamaican families.
      Furthermore, our results show that a variance components approach combined with
      structured, quantitative comparisons between families from different ethnic
      groups may be a useful strategy for helping to determine which, if any, variants
      in a small genomic region directly influence a quantitative trait.

PMID- 11331619
TI  - MECP2 truncating mutations cause histone H4 hyperacetylation in Rett syndrome.
AB  - Rett syndrome (RTT) is a mostly sporadic disorder of developmental regression,
      with loss of speech and purposeful hand use, microcephaly and seizures. It
      affects 1 in 10 000-15 000 females. RTT is caused by mutations in the MECP2 gene,
      which is located in Xq28 and subject to X inactivation. MECP2 encodes a methyl
      CpG-binding protein that binds to 5-methyl-cytosine in DNA through its methyl
      binding domain. Recruitment of a transcriptional silencing complex through
      MeCP2's transcriptional repression domain results in histone deacetylation and
      chromatin condensation. To study the effects of two common truncating RTT
      mutations (R168X and 803delG), we examined mutant MeCP2 expression and global
      histone acetylation levels in clonal cell cultures from a female RTT patient with
      the mutant R168X allele on the active X chromosome, as well as in cells from a
      male hemizygous for the frameshift mutation 803delG (V288X). Both mutant alleles
      generated stable RNA transcripts, but no intact MeCP2 protein was detected with
      an antibody against the C-terminal region of MeCP2. Western blots with antibodies
      against acetylated histones H3 and H4 revealed that H4, but not H3, was
      hyperacetylated. By using antibodies against individual acetylated lysine
      residues, the observed H4 hyperacetylation was attributed to increased
      acetylation of lysine 16. Therefore, expression of endogenous truncating MECP2
      alleles, in the absence of wild-type MeCP2 protein, is specifically associated
      with an increase in the mono-acetylated histone isoform H4K16. This observed
      effect may result in over-expression of MeCP2 target genes and, thus, play a role
      in the pathogenesis of RTT.

PMID- 11331620
TI  - Paternal monoallelic expression of PEG3 in the human placenta.
AB  - Genomic imprinting is the phenomenon whereby mono-allelic expression of certain
      genes occurs depending on their parental origin. The observation that imprinting
      only occurs in placental mammals has led to the suggestion that it may play a
      role in this form of reproduction. In the present study we have investigated the
      pattern of expression of the human PEG3 gene in the early to term placenta, as
      well as the uterus and ovary, using RT-PCR, northern blot and in situ
      hybridization. A comparison is made with the expression of Peg3 in the mouse by
      histochemical staining in betageo knock out mice. We have demonstrated high
      levels of PEG3 in the human placenta and have localized the signal to the layer
      of villous cytotrophoblast cells. In contrast, the pattern of expression of Peg3
      in the mouse placenta is less restricted, the message being present in all
      trophoblast populations. Thus, expression of PEG3/Peg3 in the human and mouse
      placenta is not directly comparable. We have also detected PEG3 message in the
      ovarian stroma. We have sequenced the human PEG3 gene from exon 3 to exon 9. By
      utilizing a polymorphism detected in exon 9, we have established that only the
      paternal allele is expressed in human placenta. Human PEG3 is therefore
      maternally imprinted as in mouse.

PMID- 11331621
TI  - Histone H2A variants and the inactive X chromosome: identification of a second
      macroH2A variant.
AB  - MacroH2A1 is an unusual variant of the core histone H2A which is enriched in
      chromatin on the inactive X chromosome of female mammals. The N-terminal third of
      the protein shares 65% amino acid identity with core histone H2A, while the
      remaining two-thirds of the protein are novel, with a small stretch of basic
      amino acids and a putative leucine zipper motif. We have now cloned a second
      macroH2A gene, encoding macroH2A2 which shares 80% amino acid identity with
      macroH2A1. Despite mapping to different chromosomes, the genomic organization of
      the macroH2A2 and macroH2A1 genes are nearly identical. The leucine zipper motif
      of macroH2A1 is not conserved in macroH2A2. Like macroH2A1, macroH2A2 forms a
      Macro Chromatin Body in the nuclei of female cells which is coincident with an X
      chromosome and co-localizes with macroH2A1. To address the distribution of other
      histone H2A variants in relation to macroH2A and the inactive X chromosome, we
      constructed a series of epitope-tagged versions of other histone H2A variants.
      Like the recently described H2A-Bbd (Barr body-deficient) variant, the histone
      variant H2A.Z was found to be deficient in chromatin on the inactive X chromosome
      in a significant proportion of female nuclei. This study provides further
      information about the nucleosomal composition of chromatin on the inactive X
      chromosome and indicates that a number of H2A variants are non-randomly
      distributed on the active and inactive X chromosomes.

PMID- 11331622
TI  - Gamete donation and anonymity: should offspring from donated gametes continue to
      be denied knowledge of their origins and antecedents?
AB  - This paper presents the case for a change from the current practice of anonymity
      and secrecy in the use of donated gametes in medically assisted conception. It
      does so by describing history of the practice, various committees of enquiry over
      the years, their recommendations for consideration of the children created and
      the need for follow-up of the outcome; presenting the evidence from outcome
      studies both about child development and family relationships where secrecy is
      maintained about the child's origin and those where the practice is openly to
      acknowledge their origins. This is followed by an analysis of the experience and
      views of these children once they are adults. In discussion of the composite
      findings recurring themes emerge. From this it is concluded that offspring from
      donated gametes should not continue to be denied knowledge of their origins and
      antecedents. In the public debate, four schools of thought are identified.
      Possible practical scenarios to implement change are discussed. This paper argues
      that the fundamental issue regarding any of these remains-that priority in
      decision-making should be the lifelong well-being of the children being created.

PMID- 11331623
TI  - Gamete donation and anonymity: the ethical and legal debate.
AB  - The British government is currently considering whether to review the law on
      information provision for donor offspring. This paper therefore provides an
      overview of the current international legal situation relating to donor anonymity
      and a review of the key arguments and evidence on both sides of the debate. While
      the British government is considering all aspects of information giving, both
      identifying and non-identifying donor information, this paper will focus on the
      most contentious issue: the provision of information that would identify the
      donor. The current legal situation in the UK and internationally is examined,
      drawing attention to a possible international trend towards more information
      giving. The evolution of the present British system is outlined and it is asked
      whether some of the concerns and values that gave rise to the practice of
      anonymous donation are still relevant today. Looking at the concept of a child's
      right to know their biological identity it examines the possible basis of such a
      right and its potential conflict with the perceived interests of the child's
      parents. Finally, some of the practical obstacles to non-anonymous donation are
      evaluated. The paper concludes that a review of the British law is both timely
      and desirable.

PMID- 11331624
TI  - Is there any physiological role for gonadotrophin oligosaccharide heterogeneity
      in humans? II. A biochemical point of view.
AB  - Heterogeneity of gonadotrophin oligosaccharides caused either by pharmacological
      intervention or which occurs naturally during normal physiological changes is
      well documented. Recent advances in structure determination of oligosaccharides
      has to some extent led to a better appreciation of how oligosaccharide
      heterogeneity may affect protein folding, stability, measurement and modulation
      of receptor binding. Here it is discussed how carbohydrate structure can impact
      upon gonadotrophin structure and function. It is well documented that
      oligosaccharides can serve as a cognate site for protein binding. One functional
      aspect of gonadotrophin glycosylation heterogeneity is the modulation of receptor
      binding affinity, yielding partially agonistic glycoforms. Carbohydrate
      heterogeneity is problematic for a clinical chemist if immunochemical assays are
      sensitive to heterogeneity. However, even measurements made without such
      interference may not accurately reflect the biological activity that is a
      collective result of all isoforms in the circulation, and perhaps of the genotype
      of each individual. Moreover, oligosaccharide heterogeneity may affect
      heterodimer stability, therefore, biological activity and immunochemical
      activity, not to mention clearance. It seems reasonable to conclude that from a
      biochemical point of view, oligosaccharide heterogeneity is of considerable
      importance. However, accurate measurement of isoforms in blood, and appropriate
      in-vitro bioassays that are insensitive to matrix effects are needed to define
      the physiological significance of each glycoform, and thereby better define
      target therapeutics and interpret diagnostic results.

PMID- 11331625
TI  - Comet assay of cumulus cell DNA status and the relationship to oocyte
      fertilization via intracytoplasmic sperm injection.
AB  - This paper postulates that in the ovary, the close association between the
      cumulus cells and the oocytes permits the fertilizing ability of the oocytes to
      be determined indirectly through cumulus cell DNA status. The objective was to
      use a modified comet assay to analyse cumulus cell DNA and relate the data to
      oocyte fertilization after intracytoplasmic sperm injection (ICSI) procedures.
      Oocytes were retrieved (n = 15 cases) and free-floating cumulus cells were pooled
      and smeared on clear glass slides to dry. Meanwhile, the denuded oocytes were
      injected with spermatozoa and fertilization was assessed, followed by embryo
      transfer. The fixed cumulus cells were stained in acridine orange, coated with a
      mini-gel agarose layer, lysed in alkaline buffer and electrophoresis performed.
      Analyses of fluorescent cell images (n = 449) showed that the tail moment was
      positively correlated to the percentage of fertilization after ICSI (r = 0.567, P
      < 0.05). In contrast, there was no correlation between tail moment and number of
      oocytes retrieved, total ampoules used, endometrial thickness and age of patient.
      The results suggested that the competence of the oocytes was associated with the
      cumulus cell DNA status. A unique feature here was the comet assay for archived
      material with obvious advantages.

PMID- 11331626
TI  - Endometrial stromal cells regulate epithelial cell growth in vitro: a new co
      culture model.
AB  - The regulation of epithelial cell function and morphogenesis by the paracrine
      effectors from the mesenchyme or stroma has been well established using in-vivo
      studies. A more complete understanding of these relationships has been delayed
      due, in part, to a lack of appropriate co-culture models. In this study, we
      describe a co-culture model which demonstrates that normal paracrine
      relationships can be reconstituted in vitro and that human endometrial stromal
      cells regulate both growth and differentiation of primary human endometrial
      epithelial cells. Interesting differences in the proliferation of stromal and
      epithelial cells were noted in response to the basement membrane extract,
      Matrigel((R)). Exposure of stromal cells to Matrigel((R)) enhanced the paracrine
      capacity of these cells in vitro. When epithelial cells were co-cultured in
      contact with stromal cells embedded in Matrigel((R)), epithelial cell growth was
      inhibited by 65-80% compared to controls. Stromal cells in contact with
      Matrigel((R)) also regulated epithelial cell differentiation, as shown by
      induction of glycodelin expression. These co-culture studies show great promise
      as a method to investigate the cellular interactions between endometrial stromal
      and epithelial cells and their environment and to understand the molecular basis
      for the regulation of normal growth and differentiation of cells within complex
      tissues such as the endometrium.

PMID- 11331627
TI  - Low-dose exogenous FSH initiated during the early, mid or late follicular phase
      can induce multiple dominant follicle development.
AB  - This prospective, randomized trial in normo-ovulatory women was designed to test
      whether administration of low-dose exogenous FSH initiated during the early, mid
      to late follicular phase can induce multiple dominant follicle development. Forty
      normal weight women (age 19-35 years, cycle length 25-32 days) participated. A
      fixed dose (75 IU/day) of recombinant FSH was started on either cycle day 3 (n =
      13), 5 (n = 13) or 7 (n = 14) until the induction of ovulation with human
      chorionic gonadotrophin. Frequent transvaginal ultrasound scans and blood
      sampling were performed. Multifollicular growth occurred in all groups (overall
      in 60%), although day 7 starters showed less multifollicular growth. Age, cycle
      length and initial FSH and inhibin B concentrations were similar between subjects
      with single or multiple follicle development. However, for all women the lower
      the body mass index (BMI), the more follicles emerged (r = -0.44, P = 0.007). If
      multifollicular growth occurred, the length of the luteal phase was reduced (P =
      0.002) and midluteal serum concentrations of LH (P = 0.03) and FSH (P = 0.004)
      were decreased and oestradiol (P = 0.002) and inhibin A (P = 0.01) were
      increased. In conclusion, interference with decremental serum FSH concentrations
      by administration of low dose FSH starting on cycle day 3, 5 or as late as day 7,
      is capable of disrupting single dominant follicle selection. The role of BMI in
      determining ovarian response suggests that differences in pharmacokinetics of
      exogenous FSH are involved. Multifollicular growth per se has a distinct effect
      on luteal phase characteristics. These observations may be relevant for the
      design of mild ovarian stimulation protocols.

PMID- 11331628
TI  - Status of peripheral blood natural killer cells in women with recurrent
      spontaneous abortions and infertility of unknown aetiology.
AB  - The aim of this study was to investigate the functional status and
      immunophenotypic characteristics of natural killer (NK) cells in women who suffer
      recurrent spontaneous abortions (RSA) or have infertility of unknown aetiology.
      Peripheral blood mononuclear cells (PBMC) were obtained from 40 study patients
      and 13 normal healthy multiparous controls. NK cells were identified using anti
      CD56 and anti-CD16 monoclonal antibodies (mAb). The expression of CD69, CD25,
      CD122, CD30, CD154, CD128 and CD94 on NK cells was detected using specific mAb
      and analysed by flow cytometry. CD69 expression on NK cells after ED(27) human
      trophoblast cell line co-culture with PBMC was also investigated. A significant
      increase in CD69 expression on CD56(+) NK cells was demonstrated in women with
      RSA (P < 0.005) and infertility (P < 0.05) as compared with that of normal
      controls. Conversely, CD94 expression was significantly decreased in women with
      RSA (P < 0.005) and infertility (P < 0.05) in comparison with that of controls.
      Increased CD69 expression on NK cells was induced after 24 h co-culture with
      ED(27). In conclusion, peripheral blood NK cells of women with RSA and
      infertility of unknown aetiology have higher proportions of activated NK cells in
      vivo. Unbalanced CD69 and CD94 expression may explain the underlying pathology.

PMID- 11331629
TI  - Basal concentrations of oestradiol may predict the outcome of in-vitro maturation
      in regularly menstruating women.
AB  - Retrospectively it was examined whether the number of retrieved oocytes, the
      maturation rate and cleavage rate can be predicted in regularly menstruating
      women by the use of the following predictive variables on cycle day 3-4: the
      concentration of FSH, oestradiol, inhibin B and inhibin A in serum and and the
      number of ovarian follicles seen by vaginal ultrasound. The study included 132
      consecutive aspirations in 100 women attending the clinic for in-vitro maturation
      due to male factor and/or tubal factor. Fifteen pregnancies were obtained after
      transfer in 83 cycles, giving a pregnancy rate of 15/132 (11%) per aspiration and
      15/83 (18%) per transfer. The concentration of FSH and the number of follicles on
      day 3 predicted the number of oocytes retrieved, whereas these parameters did not
      predict the subsequent development of oocytes. No correlation was found between
      the inhibin B, inhibin A, oestradiol and the number of oocytes respectively. The
      group with a low concentration of oestradiol on cycle day 3 (threshold <200
      pmol/l) (group 1, n = 106 cycles) had a significantly higher pregnancy rate
      compared to the group with a higher concentration (group 2, n = 26 cycles) (14
      versus 0% per aspiration, P = 0.03). The group with a low concentration of
      oestradiol was subdivided according to the concentration of inhibin A. Group 1a:
      low inhibin A (threshold <10 pg/ml, n = 84 cycles) and group 1b: high inhibin A
      concentration (> or =10 pg/ml, n = 19). The pregnancy rate in group 1a (14/84,
      17%) differed significantly from group 1b (0/19, 0%) (P = 0.03). It is concluded
      that a low basal concentration of oestradiol (<200 pmol/l) was shown to be a
      useful prognostic factor of pregnancy in IVM. The concentration of inhibin A (<10
      pg/ml) was of added value.

PMID- 11331630
TI  - Comparison of agonistic flare-up-protocol and antagonistic multiple dose protocol
      in ovarian stimulation of poor responders: results of a prospective randomized
      trial.
AB  - The management of poor responders in IVF has always been a big problem. The ideal
      approach has yet to be formulated. In this study we aim to compare two
      alternative stimulation protocols. A total of 48 poor responder patients
      described from previous cycles were included and grouped into two: group I
      consisted of 24 patients in 24 cycles in which leuprolide acetate (40 microg s.c.
      per day) was initiated on cycle day 2 followed by exogenous gonadotrophins on
      cycle day 3; group II consisted of 24 patients in 24 cycles in which ovarian
      stimulation included gonadotrophin-releasing hormone (GnRH) antagonist
      (cetrorelix, 0.25 mg daily during late follicular phase) administration. While
      only the oestradiol concentrations on the day of HCG were lower in group II
      compared with group I, the clinical pregnancy and implantation rates among groups
      did not show any significance. The impact of these two regimens in ovarian
      stimulation of poor responders seem to be same and to establish these results
      further randomized studies with larger sample sizes are required.

PMID- 11331631
TI  - Ultrasound-guided embryo transfer: immediate withdrawal of the catheter versus a
      30 second wait.
AB  - It is essential to deposit embryos as gently as possible during IVF, avoiding
      manoeuvres that might trigger uterine contractions which could adversely affect
      the results of this treatment. The time during which the embryo transfer catheter
      remains in the cervical canal might be related to stimulation of contractions.
      This study investigates the influence that the time interval before withdrawal of
      the catheter after ultrasound (US)-guided embryo deposit might have on the
      pregnancy rate in patients under IVF cycles. A total of 100 women about to
      undergo transfer of at least two optimal embryos was studied. The women were
      prospectively randomized into two groups: (i) slow withdrawal of the catheter
      immediately after embryo deposit (n = 51); and (ii) a 30 s delay before catheter
      withdrawal (n = 49). The pregnancy rates for transfer in the two groups were 60.8
      and 69.4% respectively, with no significant differences. There were no
      statistically significant differences in pregnancy rates between the two patient
      groups. The results indicate either that the waiting interval was insufficient to
      detect differences, or that the retention time before withdrawing the catheter is
      not a factor that influences pregnancy rate.

PMID- 11331632
TI  - Morbidity of first trimester aspiration termination and the seniority of the
      surgeon.
AB  - Vacuum aspiration is a safe, acceptable, and efficacious method of first
      trimester pregnancy termination. The success and complication rates are thought
      to be partially dependent on operator experience and gestation. We examined this
      further by studying the outcome of 828 consecutive surgical abortions up to 13
      weeks gestation in our hospital. The following outcomes were measured: surgical
      curettage for presumed retained products of conception; continuing pregnancy;
      uterine perforation; pelvic sepsis requiring intravenous antibiotics; and blood
      transfusion required. The complete abortion rate was 94.6% and the rate of
      continuing pregnancy 0.24%. There was a significant relationship between efficacy
      and seniority of the surgeon; consultants, senior registrars, registrars, and
      senior house officers had complete abortion rates of 97.8, 92.8, 94.7, and 88.4%
      respectively (P = 0.039). Parity did not affect efficacy. Terminations at 12-13
      weeks gestation were associated with a significantly lower complete abortion
      rate. The rates of uterine perforation, blood transfusion, pelvic sepsis
      requiring intravenous antibiotics, and overnight hospital admission were 0.24, 0,
      0.97, and 1.69% respectively. Thus, the only significant factors affecting
      outcome of surgical abortion are grade of operating surgeon or terminations
      performed at later gestations of 12-13 weeks. It is vital that physicians
      performing surgical terminations are adequately trained.

PMID- 11331633
TI  - Incidence of tail structure distortions associated with dysplasia of the fibrous
      sheath in human spermatozoa.
AB  - Dysplasia of the fibrous sheath (DFS) is an anomaly found in spermatozoa of
      severe asthenozoospermic patients. Marked hypertrophy and hyperplasia of the
      fibrous sheath is the common characteristic. Immunocytochemistry allowed us to
      visualize the distortions and incidence of tail structure abnormalities
      associated with this phenotype in six patients; four with a complete form and two
      with an incomplete form of this pathology previously diagnosed and studied by
      electron microscopy. Microtubules and fibrous sheaths were studied using
      monoclonal antibodies against alpha-acetylated tubulin and anti-FSC1 (the major
      protein component of the fibrous sheath). Mitochondrial sheaths were visualized
      using the mitochondrion-specific vital dye MitoTracker green FM(TM). Phase
      contrast and fluorescent microscopy of semen samples showed large numbers of
      spermatozoa with short, rigid, thick and irregular tails. As expected, anomalous
      and completely distorted fibrous sheaths, severe alterations of the axonemal
      microtubules and different patterns of mitochondrial sheath configurations were
      found. While ultrastructural studies of thin sections allow an in-depth knowledge
      of the internal organization of the sperm tail, fluorescence labelling of
      selected sperm components affords a unique view of the whole flagellum including
      topographical relationships of various organelles. The combination of these
      different approaches is essential for a comprehensive understanding of this
      particular pathology.

PMID- 11331634
TI  - Meiotic behaviour of the sex chromosomes in three patients with sex chromosome
      anomalies (47,XXY, mosaic 46,XY/47,XXY and 47,XYY) assessed by fluorescence in
      situ hybridization.
AB  - Meiotic studies using multicolour fluorescent in-situ hybridization (FISH) and
      chromosome painting were carried out in three patients with sex chromosome
      anomalies (47,XXY; 46,XY/47,XXY and 47,XYY). In the two patients with Klinefelter
      syndrome, although variable percentages of XXY cells (88.5 and 28.3%) could be
      found in the pre-meiotic stages, none of the abnormal cells entered meiosis, and
      all pachytenes were XY. However, the abnormal testicular environment of these
      patients probably resulted in meiotic I non-disjunction, and a certain proportion
      of post-reductional cells were XY (18.3 and 1.7%). The fact that none of the
      spermatozoa were XY also suggests the existence of an arrest at the secondary
      spermatocyte or the spermatid level. In the XYY patient, most (95.9%) premeiotic
      cells were XYY. The percentage of XYY pachytenes was 57.9%. The sex chromosomes
      were either in close proximity (XYY) or the X chromosome was separated from the
      two Ys (X + YY). A high proportion (42.1%) of post-reductional germ cells were
      XY. However, only 0.11% of spermatozoa were disomic for the sex chromosomes. In
      this case, the data suggest the existence of an arrest of the abnormal cells at
      the primary and the secondary spermatocyte or the spermatid level, giving rise to
      the continuous elimination of abnormal cells in the germ-cell line along
      spermatogenesis. The fact that the proportion of diploid spermatozoa was only
      increased in one of the three cases (XXY) is also suggestive of an arrest of the
      abnormal cell lines in these patients. The two apparently non-mosaic patients
      were, in fact, germ-cell mosaics. This suggests that the cytogenetic criteria
      used to define non-mosaic patients may be inadequate; thus, the risk of
      intracytoplasmic sperm injection in apparently non-mosaics may be lower than
      expected.

PMID- 11331635
TI  - Effects of culture system and protein supplementation on mRNA expression in pre
      implantation bovine embryos.
AB  - Assisted reproduction technologies have made great progress during the last 15
      years in most mammalian species, including humans. Growing evidence indicates
      that bovine pre-implantation development is a superior model for investigating
      early human development than the mouse. The purpose of this study was to
      investigate the effects of two basic culture systems [tissue culture medium (TCM)
      with 5% CO(2) in air or synthetic oviduct fluid (SOF) with 7% O(2), 88% N(2,) 5%
      CO(2)] and various protein supplements (serum, bovine serum albumin or polyvinyl
      alcohol) on the relative abundance of a set of developmentally important gene
      transcripts in bovine morulae and blastocysts and to compare the results with
      those for their in-vivo-derived counterparts. The basic culture system including
      the basic medium composition and oxygen tension had profound effects on the
      amounts of specific transcripts in bovine embryos, whereas the 'protein source'
      had only weak effects. Significant differences (P < or = 0.05) in the relative
      abundance of specific gene transcripts were detected between in-vivo and in-vitro
      derived embryos, especially at the morula stage. More differences were found
      between embryos produced in the TCM system and in-vivo-derived embryos than
      between SOF-generated embryos and their in-vivo counterparts. No differences were
      found in the relative abundance of gene transcripts in embryos generated under
      chemically defined conditions in the two different laboratories. It is concluded
      that the SOF system provides an environment in which pre-implantation development
      of bovine embryos is more similar to that occurring in vivo than in the TCM
      system.

PMID- 11331636
TI  - Extended embryo culture in human assisted reproduction treatments.
AB  - In order to evaluate the niche of extended embryo culture in an IVF programme,
      retrospective analysis of non-selected IVF patients, who underwent ovarian
      stimulation from April 1998 to June 1999 in a single private practice assisted
      reproductive technology centre, was performed. Embryos were cultured for 48 h in
      S1/G1.2 medium followed by 48 to 72 h of culture in S2/G2.2 to day 5 or day 6.
      Only fertilized oocytes exhibiting two pronuclei from donor and non-donor IVF and
      intracytoplasmic sperm injection (ICSI) cases were examined to determine the
      relationship between embryo cell number on day 3 and subsequent rate of
      blastocyst formation. Results indicated that a proportional relationship existed
      between the number of blastomeres present in day 3 embryos and the rate of
      blastocyst formation. Fifty-four per cent of embryos that had six cells on day 3
      formed blastocysts, while 76% of those embryos with eight cells formed
      blastocysts. Blastocyst development did not increase further when embryos had
      more than eight cells on day 3, indicating that embryos with greater cell numbers
      on day 3 are not always predictive of a greater likelihood of blastocyst
      formation. Fertilized oocytes exhibiting two pronuclei from donors produced
      significantly more blastocysts (67%) than those from IVF patients (52%; P <
      0.01), and had a significantly higher implantation rate (54%) compared with IVF
      patients (30%; P < 0.01). Furthermore, blastocyst cryopreservation resulted in
      significantly higher implantation rates than cryopreserved cleavage stage embryos
      (P < 0.001).

PMID- 11331637
TI  - Mitochondrial aggregation patterns and activity in human oocytes and
      preimplantation embryos.
AB  - Mitochondria play a vital role in the metabolism of energy-containing compounds
      in the oocyte cytoplasm to provide adenosine trisphosphate for fertilization and
      preimplantation embryo development. In this study, ratiometric confocal
      microscopy with the mitochondrion-specific membrane potential-sensitive
      fluorescence dye JC-1 (5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolyl
      carbocyanine iodide) was used to measure the activity of mitochondria in human
      oocytes and developing preimplantation embryos. Mitochondria in oocytes and
      embryos were characterized by distinct localized aggregation patterns. These
      patterns however did not determine localized regions of heterogeneity in
      mitochondrial activity. Mitochondrial activity was analysed during oocyte
      maturation and after fertilization. The activity of mitochondria in fresh
      metaphase II oocytes was negatively correlated with maternal age. This trend
      continued when the activity of developing embryos was analysed. Mitochondrial
      activity was strongly correlated with the rate of embryo development on day 3
      after fertilization, but not on day 2. Partial regression analysis showed that
      the rate of cleavage of preimplantation embryos was more highly correlated with
      embryo mitochondrial activity than maternal age. These data suggest that the
      efficiency of mitochondrial respiration in oocytes and preimplantation embryos is
      closely correlated with the programmed rate of embryo development, and suggest
      that maternal age further influences this factor. The loss of mitochondrial
      activity in oocytes obtained from ageing couples may therefore contribute to
      lower embryo development and pregnancy rates observed during cycles of IVF.

PMID- 11331638
TI  - The effect of intracytoplasmic sperm injection and semen parameters on blastocyst
      development in vitro.
AB  - The present study compares the development and quality of blastocysts derived
      from conventional oocyte insemination with those derived from intracytoplasmic
      sperm injection (ICSI). Oocytes were collected from patients undergoing ovarian
      stimulation with human menopausal gonadotrophins for IVF. Patients with normal
      semen were assigned to conventional oocyte insemination while those with
      progressive motility <20% and/or normal sperm morphology < or =4% were assigned
      to ICSI. Resulting embryos were cultured for up to 6 days. The mean number and
      percentage of embryos reaching the blastocyst stage and the mean number and
      percentage of blastocysts of high quality on days 5-6 were assessed for both
      treatment groups and compared. The influence of paternal factors (sperm
      concentration, motility, progressive motility, morphology) on blastocyst
      development and quality were assessed by regression analyses. Significantly more
      ICSI-derived embryos arrested at the 5- to 8-cell stage (P = 0.024) concomitant
      with the activation of the paternal genome than those derived from conventional
      oocyte insemination. Significantly fewer ICSI-derived embryos reached the
      blastocyst stage on days 5-6 (P<0.001) and significantly fewer ICSI-derived
      embryos were of high quality (P = 0.002) compared with conventional oocyte
      insemination. When treatment groups were combined and evaluated by regression
      analysis, progressive motility and sperm morphology were significantly correlated
      with diminished blastocyst development and quality (P < 0.05). From these data,
      we conclude that paternal factors and/or performing ICSI in cases of severe male
      factor infertility may have a detrimental effect on blastocyst development and
      their quality.

PMID- 11331639
TI  - Technical results of falloposcopy for infertility diagnosis in a large
      multicentre study.
AB  - Despite increasing evidence of its potential clinical value, falloposcopy has not
      yet found widespread use. In a large prospective international multicentre study
      we investigated the hypothesis that limited technical reproducibility may be of
      crucial significance in this regard. From 1994 to 1998, data on 367 patients with
      639 tubes were recorded from 18 centres (median number of falloposcopies 22).
      Falloposcopy was performed using hysteroscopic ostium access, coaxial tubal
      cannulation and retrograde visualization under laparoscopic control. The
      procedure was successful in 69.6% of the tubes. Failures occurred in 6.1% during
      hysteroscopy, in 10.6% during the cannulation step and in 16.4% during
      visualization. While predominantly intracavitary pathology or thick endometrium
      were found to interfere with hysteroscopic ostium access, technical
      insufficiencies resulting in catheter damage or vision disturbing light
      reflexions were identified to be responsible for most cannulation and
      visualization failures, confirming the importance of these factors. The number of
      patients who received a complete falloposcopic evaluation did not exceed 57%.
      Additionally, 23.7% of patients may have profited from unilateral success
      depending on the individual indication. As a consequence of these technically
      limited results it was concluded that the method currently qualifies for selected
      indications rather than for routine clinical application.

PMID- 11331640
TI  - A randomized controlled trial of goserelin and medroxyprogesterone acetate in the
      treatment of pelvic congestion.
AB  - Following identification of the proportion of pelvic congestion among symptomatic
      patients complaining of chronic pelvic pain, and in a totally asymptomatic group
      of patients requesting tubal ligation, the efficiency of goserelin acetate versus
      medroxyprogesterone acetate was compared objectively using pelvic venogram
      scores, and subjectively by symptom resolution, improvement of psychological
      status and sexual functioning in a prospective randomized trial in 47 patients
      with pure pelvic congestion syndrome. Patients received either goserelin acetate
      (3.6 mg/month for 6 months) or medroxyprogesterone acetate (MPA; 30 mg/day for 6
      months). Among patients with chronic pelvic pain, those with pure pelvic
      congestion were mostly parous, had the most severe pelvic signs and symptom
      scores, lowest rates of sexual functioning, and higher states of anxiety and
      depression as compared with others. At 1 year after treatment, goserelin remained
      superior to MPA in terms of pelvic venographic improvement as an objective
      measure. In alleviation of signs and symptomatology, improvement of sexual
      functioning and reduction of anxiety and depressive states as subjective
      measures, goserelin acetate achieved a statistically significant advantage (P =
      0.0001) compared with MPA.

PMID- 11331641
TI  - Does obesity diminish the positive effect of oral contraceptive treatment on
      hyperandrogenism in women with polycystic ovarian syndrome?
AB  - Polycystic ovarian syndrome (PCOS) is an obvious indication for long-term
      treatment. Combined oral contraceptives (COC) remain the first choice for the
      treatment of hyperandrogenism in most patients. However, differences in endocrine
      and metabolic parameters between obese and lean patients have been postulated.
      This is the first study evaluating the effect of COC treatment in obese versus
      non-obese PCOS patients. In total, 28 lean [body mass index (BMI) <25 kg/m(2))]
      and 15 obese (BMI >30 kg/m(2)) women patients were enrolled in the study. The
      concentrations of androgens, sex hormone-binding globulin (SHBG) and lipids were
      measured before and after 6 months of treatment with COC containing low
      androgenic progestins. Clinical androgenic symptoms were monitored. There was a
      lower concentration of SHBG in obese patients, but there were no differences in
      androgen concentrations between both groups before the study. Highly significant
      changes in concentrations of testosterone (P < 0.001), androstenedione (P <
      0.0001), SHBG (P < 0.001) and LH (P = 0.01) were demonstrated in lean patients,
      with only less significant changes in SHBG (P < 0.01) and testosterone (P < 0.05)
      in obese patients during the study. Clinical androgenic symptoms improved
      significantly (P = 0.05) only in the group of lean women. No reduction in low
      density lipoprotein-cholesterol/high-density lipoprotein-cholesterol ratio was
      observed in either group. In conclusion, the positive effect of COC treatment on
      androgen production, serum androgen binding capacity, and clinical androgenic
      symptoms was negatively influenced by an increased BMI.

PMID- 11331642
TI  - Erythropoietin concentrations are elevated in the peritoneal fluid of women with
      endometriosis.
AB  - Erythropoietin (Epo) is an important regulator of erythropoiesis and stimulates
      the proliferation of early erythroid precursors as well as the differentiation of
      late erythroid precursors of the erythroid lineage. However, recent studies have
      indicated that Epo also has angiogenic properties and plays an important role in
      the oestrogen-dependent cyclical angiogenesis within the mouse uterus. It was
      therefore postulated that Epo may be an important angiogenic factor in
      endometriosis. In order to address this hypothesis the concentration of Epo in
      peritoneal fluid (PF) was determined in patients with or without endometriosis.
      PF was collected from patients with endometriosis (n = 42) or without
      endometriosis (n = 18). Detectable concentrations of Epo were found in all PF
      samples analysed. The concentration of Epo in PF from patients with endometriosis
      was significantly higher than that in the control group (13.1 +/- 1.2 mIU/ml
      versus 7.2 +/- 0.7 mIU/ml, mean +/- SE respectively, P < 0.01). Furthermore, in
      patients with endometriosis the Epo concentrations in PF from patients with stage
      I disease (n = 17, 16.6 +/- 3.0 mIU/ml) were significantly higher than those with
      stage II (n = 8, 10.7 +/- 1.2 mIU/ml, P < 0.03), III (n = 13, 8.4 +/- 1.0 mIU/ml,
      P < 0.01), IV disease (n = 7, 7.5 +/- 1.0 mIU/ml, P < 0.01). These data suggest
      that Epo may play a role in the pathogenesis of endometriosis particularly in the
      initiation of the disease.

PMID- 11331643
TI  - Leukocyte activation in the decidua of chromosomally normal and abnormal fetuses
      from women with recurrent abortion.
AB  - As part of our continuing programme to investigate immunological causes of
      unexplained recurrent pregnancy losses, we studied subpopulations of white blood
      cells and their activation status in decidua of women with a history of recurrent
      spontaneous abortion (RSA). We differentiated specifically between normal
      karyotyped male fetuses and abnormal karyotyped fetuses with trisomy 16 because
      trisomy 16 is not compatible with life and is thus a non-controversial cause of
      spontaneous miscarriage. Leukocytes were counted in paraffin-embedded decidua
      after immunohistological staining for CD45 (LCA), CD3, CD56, CD68, CD69 and CD25.
      Numbers of activated versus non-activated T lymphocytes, NK cells and macrophages
      were compared in decidua from women with: (i) unexplained RSA who had a normal
      male karyotype (n = 17) miscarriage; (ii) unexplained RSA who had a trisomy 16 (n
      = 21) miscarriage; and (iii) normal gestationally age-matched first trimester
      pregnancies following elective termination procedures (n = 20). Significantly
      more activated leukocytes were detected in the decidua of women with unexplained
      RSA who had a normal male karyotype compared to the other groups (P < 0.0001). In
      addition, numbers of cells comprising the major leukocyte subpopulation, CD56+ NK
      cells, appeared reduced in the decidua of women with unexplained RSA compared to
      decidua from women having elective terminations. Increased numbers of activated
      leukocytes in the decidua of women with a history of unexplained recurrent
      pregnancy loss who had a normal karyotyped pregnancy provide evidence that
      cellular immunity may be involved in unexplained recurrent pregnancy loss.

PMID- 11331644
TI  - Transvaginal sonographic assessment of cervical length changes during triplet
      gestation.
AB  - The current study aimed to evaluate the contribution of transvaginal sonography
      (TVS) for monitoring cervical changes during the second half of triplet
      gestation. Forty-five pregnant women with triplets pregnancies were prospectively
      scanned by TVS from approximately 26 weeks gestation and were longitudinally
      followed-up until delivery. Based on a receiver-operating curve it was found that
      a cervical length of 25 mm is the most accurate parameter (94% sensitivity and
      45% specificity) for predicting premature delivery < or =33 gestational weeks.
      Thus, a single cervical length measurement of < or =25 mm at 26 weeks gestation
      correlated well with premature delivery at < or =33 weeks (chi(2); P = 0.002).
      Using the linear regression model, a mathematical equation [(Week of delivery =
      27.4 + 1.6 x cervical length; R(2) = 0.46; P = 0.01)] for predicting the
      gestational age of delivery (dependent variable) was determined based on mid
      gestation cervical measurements (predictors). In parturient women with triplet
      gestation, TVS assessment of the uterine cervix offers insight into the cervical
      status and provides valuable information for prenatal care. This includes both
      monitoring the cervical changes throughout third trimester as well as predicting
      the likelihood of premature delivery.

PMID- 11331645
TI  - Factor V Leiden and acquired activated protein C resistance among 1000 women with
      recurrent miscarriage.
AB  - Activated protein C (APC) resistance, both in its congenital form, due to the
      factor V Leiden mutation, and in its acquired form, are important risk factors
      for systemic venous thrombosis. In view of the suspected thrombotic aetiology of
      some cases of recurrent miscarriage, the prevalence of APC resistance was
      determined among 1111 consecutive Caucasian women with a history of either
      recurrent early miscarriage (three or more consecutive pregnancy losses at <12
      weeks gestation; n = 904) or a history of at least one late miscarriage (>12
      weeks gestation; n = 207). A control group of 150 parous Caucasian women with no
      previous history of adverse pregnancy outcome was also studied. Acquired APC
      resistance was significantly more common among both women with recurrent early
      miscarriage (8.8%: 80/904; P = 0.02) and those with late miscarriage (8.7%:
      18/207; P = 0.04) compared with controls (3.3%: 5/150). In contrast, the
      frequency of the factor V Leiden allele was similar among (i) women with
      recurrent early miscarriage (3.3%:60/1808; 58 heterozygotes and one homozygote),
      (ii) those with late miscarriage (3.9%:16/414; 14 heterozygotes and one
      homozygote) and (iii) the control group (4.0%:12/300; 12 heterozygotes). Acquired
      but not congenital APC resistance (due to the factor V Leiden mutation) is
      associated with both early and late miscarriage.

PMID- 11331646
TI  - Emotional distress of infertile women in Japan.
AB  - Although recent papers have suggested that psychological factors are implicated
      in the experience of infertility, few studies have assessed this relationship in
      a sample of Japanese infertile women. This study was carried out in order to
      clarify whether Japanese infertile women experience emotional distress. A cross
      sectional questionnaire study was performed to assess the psychological states of
      101 infertile women compared to 81 healthy pregnant women. The hospital anxiety
      and depression scale (HADS) and the profile of mood states (POMS) were
      administered. These questionnaires produced scores for depression/dejection,
      anxiety, aggression/hostility, lack of vigour, fatigue, tension anxiety, and
      confusion. The HADS and the POMS scores of infertile women were significantly
      higher than those of pregnant women, except for fatigue score. Infertile women
      with positive HADS indicating emotional disorders (39/101, 38.6%) were
      significantly (P = 0.0008, chi(2) test) more than those of pregnant women (13/81,
      16.0%) when the threshold was set at 12/13 of total HADS scores. The HADS scores
      were not affected by the women's age, duration of infertility, experience of
      conception, routine tests, and work states. In this Japanese population,
      infertile women reported higher levels of emotional distress than pregnant women,
      suggesting psychological support is needed for infertile women.

PMID- 11331648
TI  - Testicular dysgenesis syndrome: an increasingly common developmental disorder
      with environmental aspects.
AB  - Numerous reports have recently focused on various aspects of adverse trends in
      male reproductive health, such as the rising incidence of testicular cancer; low
      and probably declining semen quality; high and possibly increasing frequencies of
      undescended testis and hypospadias; and an apparently growing demand for assisted
      reproduction. Due to specialization in medicine and different ages at
      presentation of symptoms, reproductive problems used to be analysed separately by
      various professional groups, e.g. paediatric endocrinologists, urologists,
      andrologists and oncologists. This article summarizes existing evidence
      supporting a new concept that poor semen quality, testis cancer, undescended
      testis and hypospadias are symptoms of one underlying entity, the testicular
      dysgenesis syndrome (TDS), which may be increasingly common due to adverse
      environmental influences. Experimental and epidemiological studies suggest that
      TDS is a result of disruption of embryonal programming and gonadal development
      during fetal life. Therefore, we recommend that future epidemiological studies on
      trends in male reproductive health should not focus on one symptom only, but be
      more comprehensive and take all aspects of TDS into account. Otherwise, important
      biological information may be lost.

PMID- 11331649
TI  - Long-term effects on male reproduction of early exposure to common chemical
      contaminants in drinking water.
AB  - We evaluated sequelae to early exposure of male rabbits to drinking water
      containing chemicals typical of ground water near hazardous waste sites. The
      mixture (p.p.m. at 1x) was 7.75 arsenic, 1.75 chromium, 9.25 lead, 12.5 benzene,
      3.75 chloroform, 8.5 phenol and 9.5 trichloroethylene. Dutch-Belted does received
      mixture at 0x (deionized water; control), 1x or 3x as drinking water from day 20
      pregnancy through weaning. Exposure of individual males (7-9/treatment) continued
      until 15 weeks (adolescence); then, all males received deionized water. At 57-61
      weeks of age, ejaculatory capability and seminal, testicular, epididymal and
      endocrine characteristics were evaluated. At 10 opportunities with a female
      teaser, all seven control males ejaculated every time, but 12 of the 17 treated
      males failed to express interest, achieve erection and/or ejaculate on one to
      five occasions; four of the 12 accomplished ejaculation with a second male
      teaser. Total spermatozoa/ejaculate and daily sperm production were unaffected.
      However, treatment caused (P < 0.03) acrosomal dysgenesis and nuclear
      malformations. Baseline serum concentrations of LH were lower, but with
      borderline significance (P = 0.05). Testosterone secretion after exogenous human
      chorionic gonadotrophin (P < 0.04) was low. Thus, even at 45 weeks after last
      exposure to drinking water pollutants, mating desire/ability, sperm quality, and
      Leydig cell function were subnormal.

PMID- 11331650
TI  - Altered prostate growth and daily sperm production in male mice exposed
      prenatally to subclinical doses of 17alpha-ethinyl oestradiol.
AB  - Approximately 2 million women in the USA and Europe continue taking oral
      contraceptives each year during undetected pregnancy due primarily to non
      compliance and also to individual variation in sensitivity to hormones in the
      contraceptives. Prenatal exposure to oral contraceptives containing 17alpha
      ethinyl oestradiol (EE) has generally not been associated with an increased
      incidence of externally observable malformations at birth. The purpose of this
      study was to assess effects on reproductive organs in adult male mice that had
      been exposed during gestation day 0 through 17 (equivalent to gestation week 16
      in humans) to clinically relevant (approximately 0.5 microg/kg/day) and lower
      doses of EE. Doses used in this study ranged from 0.002 to 2 microg/kg/day. By 5
      months of age, prostate weight was significantly (P < 0.05) higher than controls
      in most treatment groups of EE (0.02-2 microg/kg). Prostatic androgen receptor
      populations were significantly elevated only in the 0.02 microg/kg group,
      suggesting different mechanisms for the increase in prostate weight at different
      doses. Daily sperm production (DSP) and DSP per gramme of testis were reduced in
      all treatment groups during adolescence, but not later in adulthood. These
      findings are consistent with prior studies showing that prenatal exposure of mice
      to very low doses of a number of oestrogenic chemicals can alter the adult male
      reproductive system without causing gross external malformations.

PMID- 11331651
TI  - Phytoestrogens and carcinogenesis-differential effects of genistein in
      experimental models of normal and malignant rat endometrium.
AB  - The phytoestrogen genistein was studied in normal and malignant experimental
      uterine models in vivo. The action of genistein on the uterus and vagina of
      ovariectomized DA/Han rats after 3 day oral administration (25, 50 or 100
      mg/kg/BW/d) was compared to ethinyl oestradiol (0.1 mg/kg/BW/d). Effects on
      uterine and vaginal morphology, uterine growth and uterine gene expression were
      studied. A dose dependent increase of the uterine wet weight and the uterine and
      vaginal epithelial height, a dose dependent up-regulation of complement C3, down
      regulation of clusterin mRNA expression and a stimulation of the vaginal
      cornification was observed after administration of genistein. Uterine gene
      expression and vaginal epithelium respond to genistein at doses where no
      significant effects on uterine wet weight were detectable. In general the vagina
      was more sensitive to genistein than the uterus. To analyse the action of
      genistein in malignant uterine tissue, the impact of a 28 d treatment with 50
      mg/kg/d of genistein on the in-vivo tumour growth of RUCA I endometrial
      adenocarcinoma cells, following subcutaneous inoculation into syngeneic DA/Han
      rats, was assessed. In contrast to ethinyl oestradiol (0.1 mg/kg/BW/d), a dose of
      50 mg/kg/BW/d of genistein did not affect tumour growth. Nevertheless C3 and
      TRPM2 mRNA expression in the tumour were both significantly stimulated by ethinyl
      oestradiol and genistein. In comparison to ovariectomized animals genistein up
      regulated uterine wet weight and uterine dependent gene expression in tumour
      bearing animals. In conclusion, four independent uterine and vaginal parameters
      indicate genistein is a weak oestrogen receptor agonist in the uterus and vagina
      of female DA/Han rats, and evidence is provided for a selective oestrogen
      receptor modulator (SERM)-like action of genistein in normal and malignant
      uterine tissue.

PMID- 11331652
TI  - Trends in incidence of testicular cancer and prostate cancer in Denmark.
AB  - This article presents a detailed analysis of the incidence trends of testicular
      cancer and prostate cancer, using information from the Danish Cancer Registry in
      the period 1943-1996. The rate of increase of testicular cancer was about 2.6%
      per year. The analyses indicated that incidence was more strongly dependent on
      the man's birth cohort than on the calendar period. The analysis confirmed the
      significantly reduced incidence of testicular cancer in the 1943 cohort and
      suggested a levelling off in the increase in testicular cancer incidence from
      cohorts born after around 1963. This may imply that the great part of the recent
      increase in incidence has been due to a rapid increase in incidence in successive
      birth cohorts born in the relatively short period from 1945 to 1960. The rate of
      increase of prostate cancer was about 1.6% per year. The analyses indicated a
      stronger dependency on period than on birth cohort. The cohort parameters had
      very low values in the three earliest cohorts (1858-1868) and the period
      parameters showed a low incidence in the most recent period. The epidemiological
      pattern of prostate cancer incidence seems dominated by changes in diagnosis and
      registration and does not permit inferences about changes in causal factors.

PMID- 11331653
TI  - Regional differences in semen quality in Europe.
AB  - Recent reports have indicated a decrease in semen quality of men in some
      countries, and suggested regional differences. A study was undertaken of semen
      samples from 1082 fertile men from four European cities (Copenhagen, Denmark;
      Paris, France; Edinburgh, Scotland; and Turku, Finland). Semen analysis was
      standardized, inter-laboratory differences in assessment of sperm concentration
      were evaluated, and morphology assessment centralized. Lowest sperm
      concentrations and total counts were detected for Danish men, followed by French
      and Scottish men. Finnish men had the highest sperm counts. Men from Edinburgh
      had the highest proportion of motile spermatozoa, followed by men from Turku,
      Copenhagen and Paris. Only the differences between Paris/Edinburgh and
      Paris/Turku were statistically significant (P < 0.003 and P < 0.002
      respectively). No significant differences in morphology were detected. A general
      seasonal variation in sperm concentration (summer 70% of winter) and total sperm
      count (summer 72% of winter) was detected. Semen quality of a 'standardized' man
      (30 years old, fertile, ejaculation abstinence of 96 h) were estimated.
      Typically, sperm concentrations (x 10(6)/ml) for winter/summer were: Turku
      132/93; Edinburgh 119/84; Paris 103/73; and Copenhagen 98/69. These differences
      in semen quality may indicate different environmental exposures or lifestyle
      changes in the four populations. However, it remains to be seen whether such
      changes can account for these differences. These data may also serve as a
      reference point for future studies on time trends in semen quality in Europe.

PMID- 11331654
TI  - Sexual precocity after immigration from developing countries to Belgium: evidence
      of previous exposure to organochlorine pesticides.
AB  - In a retrospective auxological study of 145 patients seen in Belgium during a 9
      year period for treatment of precocious puberty, 28% appeared to be foreign
      children (39 girls, one boy) who immigrated 4 to 5 years earlier from 22
      developing countries, without any link to a particular ethnic or country
      background. The patients were either adopted (n = 28) or non-adopted (n = 12),
      the latter having normal weight and height at immigration and starting early
      puberty without evidence of earlier deprivation. This led to the hypothesis that
      the mechanism of precocious puberty might involve previous exposure to
      oestrogenic endocrine disrupters. A toxicological plasma screening for eight
      pesticides detected p,p'-DDE, which is derived from the organochlorine pesticide
      DDT. Median p,p'-DDE concentrations were respectively 1.20 and 1.04 ng/ml in
      foreign adopted (n = 15) and non-adopted (n = 11) girls with precocious puberty,
      while 13 out of 15 Belgian native girls with idiopathic or organic precocious
      puberty showed undetectable concentrations (<0.1 ng/ml). A possible relationship
      between transient exposure to endocrine disrupters and sexual precocity is
      suggested, and deserves further studies in immigrant children with non-advanced
      puberty.

PMID- 11331655
TI  - Reassessment of models used to test xenobiotics for oestrogenic potency is
      overdue.
AB  - Product safety bioassays need to include data from animals with susceptible
      genotypes or the potential for environmental compounds to disrupt reproductive
      development in hormonally sensitive populations may be greatly underestimated.
      The continued use of resistant animal models is likely to result in allowable
      releases of toxic levels of oestrogenic agents that could differentially disrupt
      reproductive development and function of sensitive genotypes, leading to
      reproductive failure and loss or extinction of susceptible individuals,
      populations and species. Rather than ignoring the role of genetic differences in
      susceptibility to oestrogenic agent-induced carcinogenicity and endocrine
      disruption, government agencies should support efforts to identify the genetic
      mechanisms involved in these responses, and to screen for and develop strains of
      mice and rats which are sensitive to the induction of
      genotoxicity/carcinogenicity as well as the inhibition of reproductive
      development and function by oestrogenic agents. Such sensitive strains would be
      even more optimal for testing chemicals for endocrine disruptor activity.

PMID- 11331656
TI  - Assessment of oestrogenic potency of chemicals used as growth promoter by in
      vitro methods.
AB  - Three in-vitro bioassays were used to compare the oestrogenic potency of
      chemicals used as growth promoter in beef cattle in certain non-European Union
      countries (17beta-oestradiol, alpha-zearalanol, testosterone, trenbolone,
      trenbolone acetate, melengestrol acetate) or found as food contaminant such as
      the mycotoxin zearalenone and some of their metabolites (17alpha-oestradiol,
      oestrone, 17alpha-epitestosterone, 19-nortestosterone, androstendione,
      zearalanone, alpha-zearalanol, beta-zearalanol, alpha-zearalenol, beta
      zearalenol). The strong oestrogens 17alpha-ethinyl oestradiol and
      diethylstilboestrol were used as standards. The first bioassay was based on the
      activation of a reporter gene by oestrogens in recombinant yeast expressing human
      or rainbow trout oestrogen receptor. In the second bioassay, the vitellogenin
      gene induction of rainbow trout hepatocyte cultures was used as a biomarker for
      the exposure to oestrogens. The third bioassay was based on the alkaline
      phosphatase gene induction by oestrogens in the human endometrial Ishikawa cell
      line. The assessment of oestrogenic potency of these chemicals clearly
      demonstrates the strong oestrogenicity of the mycotoxin zearalenone and its
      metabolites and particularly alpha-zearalenol which was as potent as ethinyl
      oestradiol and diethylstilboestrol in the human endometrial Ishikawa cell line.

PMID- 11331658
TI  - High rates of cramping with misoprostol administration for intrauterine
      insemination.

PMID- 11331657
TI  - Oestrogenic potencies of Zeranol, oestradiol, diethylstilboestrol, Bisphenol-A
      and genistein: implications for exposure assessment of potential endocrine
      disrupters.
AB  - We have compared the oestrogenic potency of the synthetic oestrogen Zeranol, used
      as a growth promoter in meat production, and five related compounds, with the
      potency of 17beta-oestradiol, diethylstilboestrol (DES), genistein, and Bisphenol
      A. The potency was assayed by analysing differences in expression levels of
      endogenous oestrogen-regulated genes in human MCF7 cells, treated with different
      concentrations of the compounds. Zeranol, 17beta-oestradiol and DES were about
      equally potent, genistein was four to six orders of magnitude less potent than
      17beta-oestradiol but an order of magnitude more potent than Bisphenol-A. There
      were gene specific differences, the PS2 and TGFbeta3 genes were about equally
      sensitive to Zeranol, 17beta-oestradiol and DES whereas a down-regulation of
      MRG1/p35srj could be detected at fmol/l concentrations of Zeranol whereas 17beta
      oestradiol was several orders of magnitude less potent. GST mu3 was sensitive to
      fmol/l concentrations of 17beta-oestradiol but much less sensitive to Zeranol and
      DES. The very high potency of Zeranol compared with other potential endocrine
      disrupters suggests that Zeranol intake from beef products could have greater
      impact on consumers than the amounts of the known or suspected endocrine
      disrupters that have been found in food. Since little data is available in man,
      there is an urgent need for reliable measurements of the concentration of Zeranol
      in human serum after ingestion of meat products from treated animals.

PMID- 11331659
TI  - Routine postcoital testing is unnecessary.

PMID- 11331662
TI  - Hypospadias and the androgen receptor gene: mutation screening and CAG repeat
      length analysis.
AB  - We report on mutation screening and CAG repeat length analysis of the androgen
      receptor (AR) gene in 21 patients with hypospadias. The urethral meatus was
      located at the glandular region in six patients (glandular type), at the penile
      shaft in seven patients (penile type), and at the scrotal/perineal region in
      eight patients (scrotal/perineal type). Mutation screening was performed for
      exons 1-8 and their flanking introns (except for the CAG and GGC repeat regions
      at exon 1) by the heteroduplex detection method and showed no abnormal
      chromatograms. The CAG repeat length analysis was carried out using 50 normal
      boys and 50 fertile males as controls, and demonstrated no statistically
      significant difference in the median of CAG repeat lengths or in the frequency of
      long CAG repeats (> or = 26 or > or = 28) between the controls and the patients
      with the three different types of hypospadias. The results suggest that AR gene
      abnormalities do not constitute a major factor in the development of hypospadias.

PMID- 11331661
TI  - Expression of Bcl-2 family proteins and spontaneous apoptosis in normal human
      testis.
AB  - We investigated the frequency of spontaneous apoptosis and expression of the Bcl
      2 family of proteins during normal spermatogenesis in man. Testicular tissue with
      both normal morphology and DNA content was obtained from necro-donors and fixed
      in Bouin's solution. A TdT-mediated dUTP end-labelling method (TUNEL) was used
      for the detection of apoptotic cells. Expression of apoptosis regulatory Bcl-2
      family proteins and of p53 and p21(Waf1) was assessed by immunohistochemistry.
      Germ cell apoptosis was detected in all testes and was mainly seen in primary
      spermatocytes and spermatids and in a few spermatogonia. Bcl-2 and Bak were
      preferentially expressed in the compartments of spermatocytes and differentiating
      spermatids, while Bcl-x was preferentially expressed in spermatogonia. Bax showed
      a preferential expression in nuclei of round spermatids, whereas Bad was only
      seen in the acrosome region of various stages of spermatids. Mcl-1 staining was
      weak without a particular pattern, whereas expression of Bcl-w, p53 and p21(Waf1)
      proteins was not detected by immunohistochemistry. The results show that
      spontaneous apoptosis occurs in all male germ cell compartments in humans. Bcl-2
      family proteins are distributed preferentially within distinct germ cell
      compartments suggesting a specific role for these proteins in the processes of
      differentiation and maturation during human spermatogenesis.

PMID- 11331663
TI  - Distinct regulation of gene expression by prostaglandin F(2alpha) (PGF(2alpha))
      is associated with PGF(2alpha) resistance or susceptibility in human granulosa
      luteal cells.
AB  - The effects of human chorionic gonadotrophin (HCG) and prostaglandin F(2alpha)
      (PGF(2alpha)) on regulation of human granulosa-luteal cell (GLC) function at
      different stages of differentiation (day 2 versus day 8 of culture) were studied.
      Expression of LH receptor mRNA and biosynthesis of progesterone were HCG
      dependent in human GLC at all stages (n = 6, P < 0.05). Steady-state
      concentrations of mRNA encoding for FP (a specific high-affinity plasma membrane
      receptor for PGF(2alpha)) were not dependent on, but were stimulated by, addition
      of HCG (10 IU/ml) or 8-bromo-cAMP (0.5 mmol/l) (n = 6, P < 0.05). Treatment with
      PGF(2alpha) (100 nmol/l) decreased FP mRNA concentration, but had no effect on LH
      receptor and cyclo oxygenase-2 (COX-2) expression on day 2 of cultured GLC (n =
      8). As a result, the progesterone biosynthesis by GLC was not affected. On day 8,
      PGF(2alpha) induced FP and PGHS-2 expression and at the same time decreased LH
      receptor expression, resulting in inhibition of progesterone output by GLC. Our
      data demonstrated that early stage GLC (day 2 of culture) are resistant to
      PGF(2alpha)-induced inhibition of progesterone synthesis but underwent further
      differentiation and acquired luteolytic capacity after 8 days culture in vitro.
      We conclude that, via distinct gene regulation at different stages of
      differentiation, human GLC may become resistant or susceptible to PGF(2alpha)
      induced luteolysis.

PMID- 11331664
TI  - Mitochondrial DNA content affects the fertilizability of human oocytes.
AB  - Mitochondrial DNA content varies considerably in oocytes, even when collected
      from the same patient. In the present study, real-time quantitative polymerase
      chain reaction analysis of 113 unfertilized oocytes obtained from 43 patients
      revealed an average of 193,000 (range: 20,000 to 598,000) mitochondrial genomes
      per cell. We compared several groups of oocytes to investigate the relationship
      between mitochondrial DNA content and fertilizability. The average mitochondrial
      DNA copy number was significantly lower in cohorts suffering from fertilization
      failure compared to cohorts with a normal rate of fertilization. In addition, the
      mitochondrial copy number of oocytes from patients with fertilization failure due
      to unknown causes was significantly lower than that of oocytes from patients in
      which IVF failure was due mainly to a severe sperm defect. The lower mtDNA copy
      number could be due to defective cytoplasmic maturation of oocytes. We conclude
      that low mitochondrial DNA content, due to inadequate mitochondrial biogenesis or
      cytoplasmic maturation, may adversely affect oocyte fertilizability.

PMID- 11331665
TI  - Expression of Fas and Fas ligand mRNA in rat and human preimplantation embryos.
AB  - The Fas-Fas ligand (L) system is one of the major signalling pathways to induce
      apoptosis in various cells and tissues. The aim of this study was to investigate
      the expression of the Fas-Fas L system in rat and human oocytes and
      preimplantation embryos. We determined the expression of Fas and Fas L mRNA of
      rat oocytes and embryos up to the blastocyst stage, and of human embryos at the 2
      or 4-cell stage, using reverse transcription polymerase chain reaction (PCR) and
      nested PCR techniques. Moreover, we investigated the expression of Fas mRNA in
      human fragmented embryos. In rat embryos, Fas mRNA was expressed at the 2-cell
      stage only, whereas Fas L mRNA was expressed in oocytes, and at the pronuclear (1
      cell) and 2-cell stages. In human embryos, Fas mRNA was expressed at the 4-cell
      stage only, whereas Fas L mRNA was expressed at both 2- and 4-cell stages. Human
      fragmented embryos expressed both Fas and Fas L mRNA. Because simultaneous
      expression of Fas and Fas L mRNA occurred in 2-cell rat embryos and in 4-cell
      human embryos, the Fas-Fas L system might be involved in the apoptotic pathway in
      the early embryos of these species.

PMID- 11331667
TI  - Expression of the second isoform of gonadotrophin-releasing hormone (GnRH-II) in
      human endometrium throughout the menstrual cycle.
AB  - We examined the expression of the protein and mRNA of the newly cloned isoform of
      human gonadotrophin-releasing hormone (GnRH-II) in the normal human endometrium
      during the menstrual cycle. Nested RT-PCR and sequence analysis revealed that two
      spliced variants of GnRH-II mRNA were expressed during the entire menstrual
      cycle, with the shorter transcript having a 21 nucleotide deletion in the region
      coding for GnRH-associated peptide. Using immunohistochemistry, we identified
      immunoreactive GnRH-II in both stromal and glandular epithelial cells during the
      entire menstrual phase. The immunostaining intensity was stronger during the
      early and mid-secretory phase compared with the proliferative and late-secretory
      phase. A large amount of immunoreactive GnRH-II was localized in the apical pole
      of the glandular lumen. Our results show that the second isoform of GnRH (GnRH
      II) is expressed in the human endometrium during the entire menstrual phase. We
      also suggest that an increased expression of endometrial GnRH-II peptide, noted
      during the early and mid-secretory phase, may play an important role in human
      embryo implantation.

PMID- 11331666
TI  - Changes in expression and subcellular localization of nuclear retinoic acid
      receptors in human endometrial epithelium during the menstrual cycle.
AB  - The endometrium is a uniquely dynamic tissue in that it undergoes monthly cycles
      of proliferation and secretory activity, and is regulated by ovarian steroid
      hormones. In this study, we focused on retinoic acid receptors (RAR and RXR)
      which are ligand-dependent transcription factors belonging to the large family of
      steroid hormones and are expected to affect to cell growth and differentiation in
      the endometrium. We analysed the expression and subcellular localization of the
      RA receptors in 57 samples of human endometrium by immunohistochemistry and
      Western blotting. In the nuclei of the endometrial epithelium, the RA receptors
      were expressed strongly in the proliferative phase. However, RAR were drastically
      reduced in the epithelial nuclei during the secretory phase in association with
      changes in serum oestradiol and in the expression of the oestrogen receptor. The
      expression of RXR was localized in the epithelial nuclei throughout the menstrual
      cycle. Confocal laser scanning microscopical observation clearly showed the
      difference in the localization between RAR and RXR in the secretory phase.
      Furthermore the findings of immuno-electron microscopy showed pooled RAR around
      the rough endoplasmic reticulum, suggesting that transport of these receptors to
      the nuclei is inhibited. These findings suggest that RAR and RXR work mainly in
      the proliferative phase and that in the endometrium RXR may play a different role
      to RAR during the secretory phase.

PMID- 11331668
TI  - Expression of epithelial neutrophil-activating peptide 78 in cultured human
      endometrial stromal cells.
AB  - It has been demonstrated that human endometrial stromal cells (ESC) produce a
      variety of chemokines in vivo and in vitro. To evaluate the expression of
      epithelial neutrophil-activating peptide 78 (ENA-78) in the endometrium,
      concentrations of ENA-78 in cyclic endometrial tissues were measured using enzyme
      linked immunosorbent assay. The expression of ENA-78 was also detected in cyclic
      endometrium by immunohistochemistry. Endometrial tissues in the secretory phase
      contained higher amounts of ENA-78 protein than did those in the proliferative
      phase. Immunofluorescence staining revealed that ENA-78 protein was localized
      mainly in the stroma of endometrium. In addition, to evaluate the involvement of
      inflammatory mediators and ovarian steroid hormones in the production of ENA-78
      by ESC was evaluated by in-vitro studies. Unstimulated ESC constitutively
      secreted ENA-78. Progesterone, lipopolysaccharide, tumour necrosis factor-alpha,
      and interleukin-1beta significantly stimulated the expression of ENA-78 by ESC.
      It is suggested that the production of ENA-78 by ESC is regulated by progesterone
      as well as by the inflammatory mediators. The modulation of ENA-78 concentration
      in the local environment by these mediators may contribute to the normal and
      pathological processes of human reproduction through regulation of leukocyte
      trafficking into the endometrium.

PMID- 11331669
TI  - Increased concentrations of cathepsin D in peritoneal fluid from women with
      endometriosis.
AB  - To assess the release of the proteolytic enzyme cathepsin D in endometriosis,
      concentrations in peritoneal fluid and serum were measured by ELISA in 54 women
      with (n = 33) and without (n = 21) endometriosis. Surgery was scheduled in either
      the proliferative or secretory phase of the menstrual cycle. The concentrations
      of cathepsin D in the peritoneal fluid were markedly elevated in the
      endometriosis patients (median 58 ng/ml, interquartile range 0-166 ng/ml) as
      compared to the controls (5 ng/ml, 0-86 ng/ml), especially in women with late
      stage disease (n = 19, stages III/IV) and in those not undergoing gonadotrophin
      releasing hormone (GnRH) agonist therapy (n = 15). No significant difference was
      determined in cathepsin D concentrations of the serum from women with and without
      endometriosis. We conclude that cathepsin D is an important factor that may
      contribute to the pathogenesis of endometriosis, possibly by promoting digestion
      of extracellular matrix proteins. These results have implications for the
      therapeutic efficacy of GnRH agonists.

PMID- 11331670
TI  - Regional and cellular localization of osteonectin/SPARC expression in connective
      tissue and cytotrophoblastic layers of human fetal membranes at term.
AB  - Fetal membranes overlying the cervix in patients prior to and during labour, and
      within the rupture tear after spontaneous delivery at term, exhibit altered
      morphology. In this study we report that in comparison to mid-zone fetal
      membranes biopsies, these regions are characterized by increased expression of
      the matricellular protein osteonectin or SPARC (Secreted Protein Acidic and Rich
      in Cysteine). In the reticular layer, the percentage of vimentin positive
      mesenchymal cells immunoreactive for osteonectin increased in these regions from
      3-4% to 25-33% and represented a fraction of the alpha-smooth muscle actin
      positive myofibroblasts elevated in the same regions. In the fibroblastic layer,
      the percentage of osteonectin positive cells increased from 1-5% to 8-13%;
      however, these did not exhibit the same relationship to the alpha-smooth muscle
      actin positive myofibroblasts in this layer. In the cytotrophoblastic layer the
      percentage of cytotrophoblastic cells immunoreactive for osteonectin increased
      from 1% to 6-12%. Elevation of in-situ detectable mRNA was also observed in the
      same cellular populations in this region. The incidence of cells positive for
      osteonectin mRNA or protein in the reticular layer correlated with morphological
      changes. Osteonectin has been implicated in the regulation of extracellular
      matrix turnover, and its pattern of expression suggests a role in the regional
      connective tissue and cytotrophoblastic changes proposed to be involved in the
      cleavage and rupture of fetal membranes.

PMID- 11331672
TI  - FISH analysis of the chromosomal status of spermatozoa from three men with
      45,XY,der(13;14)(q10;q10) karyotype.
AB  - Meiotic segregation of chromosomes 13 and 14 was studied in the ejaculated
      spermatozoa of three men carrying a translocation der(13;14)(q10;q10). The
      spermatozoa of these patients and of a donor with a normal 46,XY karyotype
      (control) were analysed by two-colour fluorescent in-situ hybridization (FISH)
      with specific chromosomal painting of chromosomes 13 and 14, by two-colour FISH
      detecting chromosomes 18 and 21 and by triple-colour FISH for chromosomes X, Y
      and 8. For patients 1, 2 and 3, respectively, 81.34, 82.60 and 88.90% of the
      analysed nuclei showed normal or balanced chromosomal status, resulting from the
      alternate segregation of the translocation. The rates of spermatozoa with an
      unbalanced status (disomy and nullisomy, 13 or 14) resulting from the adjacent
      mode of segregation were estimated respectively at 18.06, 16.32 and 10.80 (for
      patients 1, 2 and 3). Additional colour FISH analysis with probes specific for
      chromosomes X, Y, 8, 18 and 21 showed a significant increase in some disomy
      frequencies (8, 18, 21, X and Y for patient 1, only 18 for patient 2) in
      comparison with the control. These results would seem to indicate an
      interchromosomal effect.

PMID- 11331671
TI  - Effects of platelet-activating factor on cytokine production by human uterine
      cervical fibroblasts.
AB  - Platelet-activating factor (PAF), a lipid that acts as a potent proinflammatory
      mediator, is involved in several reproductive processes including parturition. To
      investigate the effects of PAF on expression of various cytokines by cultured
      human uterine cervical fibroblasts obtained at term prior to labour, Northern
      blot analyses and enzyme-linked immunosorbent assays were performed. C-PAF, a
      stable analogue of PAF, increased expression of interleukin-6 and -8 mRNA in a
      dose-dependent manner (10(-10) to 10(-8) mol/l of C-PAF), and the expression
      peaked within 4 h. The corresponding protein concentrations were increased in
      culture media. Monocyte chemoattractant protein-1 mRNA showed marked induction by
      10(-8) mol/l of C-PAF; this peaked by 4 h and was followed by an increase in the
      protein concentration. Another cytokine, RANTES (regulated upon activation,
      normal T cell expressed and secreted) showed marked mRNA induction by 10(-8)
      mol/l of C-PAF, and continued to increase in a time-dependent manner until 24 h.
      The protein concentration was correspondingly increased in the medium. The PAF
      induced cytokine production was abolished by co-incubation with WEB 2170, a
      specific PAF receptor antagonist. PAF may stimulate local production of cytokines
      which may induce migration of leukocytes and accelerate collagenolysis in the
      uterine cervix, thus contributing to cervical ripening during parturition.

PMID- 11331673
TI  - Single cell multiplex PCR amplification of five dystrophin gene exons combined
      with gender determination.
AB  - Large deletions in the dystrophin gene account for > 60% of mutations responsible
      for Duchenne muscular dystrophy (DMD). We have developed a genetic test that can
      be used directly for the preimplantation genetic diagnosis (PGD) of a majority of
      couples at risk of transmitting DMD. The test, a double nested multiplex
      polymerase chain reaction assay for the amplification of exons 8, 19, 45, 47 and
      51 allows the detection of over 70% of all DMD deletions. Amelogenin sequences on
      the X and the Y chromosomes were also co-amplified to provide a correlation
      between embryo gender and deletion status. The setting up of reliable single cell
      assays for preimplantation genetic diagnosis is delicate and time consuming.
      Assays have to be validated on a large number of single cells for each specific
      mutation to assess efficiency and accuracy before being applied clinically. The
      multiplex procedure permitted the validation of all tested loci in the same
      series of isolated lymphocytes rather than in separate series for each exon. One
      hundred single lymphocytes, 50 female and 50 male cells, were analysed with an
      overall amplification rate of 98% and an amplification failure of 2% per exon. We
      suggest that this test is reliable, easy to set up and much preferable to a mere
      sex determination with the selective transfer of female embryos.

PMID- 11331675
TI  - Evaluation and management of children younger than two years old with apparently
      minor head trauma: proposed guidelines.
AB  - OBJECTIVE: In children <2 years old, minor head trauma (HT) is a common injury
      that can result in skull fracture and intracranial injury (ICI). These injuries
      can be difficult to detect in this age group; therefore, many authors recommend a
      low threshold for radiographic imaging. Currently, no clear guidelines exist
      regarding the evaluation and management of head-injured infants. We sought to
      develop guidelines for management based on data and expert opinion that would
      enable clinicians to identify children with complications of HT and reduce
      unnecessary imaging procedures. METHODS. EVIDENCE: References addressing
      pediatric HT were generated from a computerized database (Medline). The articles
      were reviewed and evidence tables were compiled. EXPERT PANEL: The
      multidisciplinary panel was comprised of nine experts in pediatric HT. CONSENSUS
      PROCESS: A modified Delphi technique was used to develop the guidelines. Before
      the one meeting, panel members reviewed the evidence and formulated answers to
      specific clinical questions regarding HT in young children. At the meeting,
      guidelines were formulated based on data and expert consensus. RESULTS: A
      management strategy was developed that categorizes children into 4 subgroups,
      based on risk of ICI. Children in the high-risk group should undergo a computed
      tomography (CT) scan. Those in the intermediate risk group with symptoms of
      possible ICI should either undergo CT scan or observation. Those in the
      intermediate risk group with some risk for skull fracture or ICI should undergo
      CT and/or skull radiographs or observation. Those in the low-risk group require
      no radiographic imaging. CONCLUSIONS: We have developed a guideline for the
      evaluation of children <2 years old with minor HT. The effect of these guidelines
      on clinical outcomes and resource utilization should be evaluated.

PMID- 11331676
TI  - Thirteen-year follow-up of children and adolescents with chronic fatigue
      syndrome.
AB  - OBJECTIVE: To describe the educational, social, and symptomatic outcome of
      children and adolescents with chronic fatigue syndrome 13 years after illness
      onset. METHODS: Between January 1984 and December 1987, 46 children and
      adolescents developed an illness suggestive of chronic fatigue syndrome. Follow
      up questionnaires were obtained from 35 participants an average of 13 years after
      illness onset. Data were obtained concerning subsequent medical diagnoses, amount
      of school missed, presence and severity of current symptoms, and subjective
      assessment of degree of illness resolution. RESULTS: Of the 35 participants, 24
      were female (68.6%) and 11 were male (31.4%). Average age at illness onset was
      12.1 years. Eight participants (22.9%) had an acute onset of symptoms, 27 (77.1%)
      had a gradual onset. No participant received an alternative medical diagnosis
      that could have explained the symptom complex between illness onset and follow
      up. Thirteen participants (37.1%) considered themselves resolved of illness at
      follow-up; 15 participants (42.9%) considered themselves well but not resolved; 4
      (11.4%) considered themselves chronically ill; and 3 (8.6%) considered themselves
      more ill than during the early years of illness. Correlation with the Medical
      Outcomes Study Short Form Health Survey was good for current level of symptoms
      and degree of recovery. Eight participants (22.9%) missed >2 years of school, and
      5 of these were still ill at follow-up. Amount of school missed correlated with
      both illness severity at follow-up and perceived social impact of the illness.
      CONCLUSIONS: These data demonstrate the presence of an illness consistent with
      the current definition of chronic fatigue syndrome. Eighty percent of children
      and adolescents affected had a satisfactory outcome from their fatiguing illness,
      although the majority of these participants had mild to moderate persisting
      symptoms. Twenty percent of participants remain ill with significant symptoms and
      activity limitation 13 years after illness onset. Chronic fatigue syndrome in
      children and adolescents may result in persistent somatic symptoms and disability
      in a minority of those affected.

PMID- 11331677
TI  - Risk factors for latent tuberculosis infection among children in New York City.
AB  - OBJECTIVE: Although identification and appropriate treatment of children with
      latent tuberculosis (TB) infection (LTBI) is considered critical to the control
      and elimination of TB in the United States, there are limited data on risk
      factors for LTBI in pediatric populations. METHODS: To further improve targeted
      screening for LTBI, we performed a matched case-control study from September 1996
      to December 1998. We actively surveyed 24 primary care clinics serving Northern
      Manhattan and Harlem twice monthly for case participants 1 to 5 years old with
      LTBI, defined as a child with a Mantoux tuberculin skin test (TST) >/=10 mm and a
      normal chest radiograph. Two age- and clinic-matched control participants with
      TSTs equal to 0 mm were enrolled per case. To determine risk factors for LTBI, a
      bilingual research worker reviewed the medical records of study participants and
      administered a questionnaire to the parents of participants. RESULTS: We enrolled
      96 cases and 192 controls whom did not differ by age, gender, ethnicity, and
      race; overall, the mean age of participants was 2.9 years, 51% were male, 80%
      were Hispanic, and 9% black. Logistic regression analysis demonstrated that
      contact with an adult with active TB, foreign birth, foreign travel, and a
      relative with a positive TST were predictive of case status. In contrast, a
      history of a previous negative TST proved protective and BCG immunization was not
      an independent risk factor for a positive TST, suggesting that boosting was not
      important in this population. CONCLUSIONS: We identified several risk factors for
      LTBI in children that can be used to refine targeted surveillance for TB among
      Hispanic immigrant populations in the United States.

PMID- 11331678
TI  - Obstructive nephropathy in children: long-term progression after relief of
      posterior urethral valve.
AB  - BACKGROUND: Approximately one third of children with end-stage renal disease have
      the illness because of urinary tract malformations, obstructive uropathy, and
      hypoplasia/dysplasia. The significant drop in infant mortality from obstructive
      uropathies in recent decades, attributable to prenatal diagnosis with renal
      ultrasonography and coordinated surgical and medical care, necessitated a
      reevaluation of the long-term outcome. METHODS: To that end, we examined the long
      term progression of obstructive nephropathy after neonatal relief of posterior
      urethral valves in our center over a span of 21 years, with diagnosis and care
      being provided by the same pediatric and urology team. RESULTS: The 10
      consecutive cases of posterior urethral valves represented 7% of all patients
      with congenital malformative uropathies seen over this period. The following
      procedures were performed: primary valve ablation (90%) and vesicostomy (40%).
      Seventy percent of patients progressed to end-stage renal disease over a (mean +/
      standard error of the mean) follow-up of 11.3 +/- 2.1 years. The linear plot of
      the log of the inverse of serum creatinine versus time suggested unrelenting
      progression. The rate of progression was rapid after serum creatinine exceeded 5
      mg/dL but the rate was slow and steady from serum creatinine of 1.5 to 5 mg/dL.
      CONCLUSIONS: To test the effect of a therapeutic intervention to ameliorate the
      rate of progression, this steady and prolonged progression of 0.5 mg/dL per year
      between serum creatinine concentration of 1.5 to 5 mg/dL would seem the optimal
      study.

PMID- 11331679
TI  - Lice, nits, and school policy.
AB  - BACKGROUND: The epidemiology of head lice infestation is poorly understood. Many
      schools treat all children with nits as though they are contagious. Children with
      nits but no lice are often removed from school until they are treated and all
      visible nits are removed. OBJECTIVE: To investigate the probability that children
      with nits alone will become infested with lice. DESIGNS: Prospective cohort
      study. SETTING: Two metropolitan Atlanta elementary schools. PARTICIPANTS: A
      total of 1729 children were screened for head lice. Twenty-eight children (1.6%)
      had lice, whereas 63 (3.6%) had nits without lice. Fifty of the 63 children (79%)
      with nits alone completed follow-up. OUTCOME MEASURE: Conversion (ie, becoming
      infested with lice) within 14 days after initial screening. RESULTS: Nine of 50
      children (18.0%) followed for nits alone converted. Although children who
      converted did not have significantly more nits than did nonconverters, having
      nits near the scalp was a risk factor for conversion. Seven of 22 children
      (31.8%) with >/=5 nits within one fourth inch of the scalp converted, compared
      with 2 of 28 children (7.1%) with fewer (relative risk: 4.45; 95% confidence
      interval: 1.03-19.35). This risk remained statistically significant after
      separately stratifying for sex, recent treatment, and total number of nits.
      CONCLUSIONS: Although having >/=5 nits within one fourth inch of the scalp was a
      risk factor for conversion, most children with nits alone did not become
      infested. Policies requiring exclusion from school and treatment for all children
      with nits alone are likely excessive. Instead, these children may benefit from
      repeated examination to exclude the presence of crawling lice.lice, pediculus,
      lice infestations, pediatrics, school.

PMID- 11331681
TI  - Methemoglobinemia and consumption of vegetables in infants.
AB  - OBJECTIVE: To assess clinical and epidemiologic data of 7 infants diagnosed with
      acquired methemoglobinemia at the pediatric emergency department between 1993 and
      1998. All cases were attributed to the consumption of mixed vegetables. METHODS:
      Medical records were reviewed to collect anamnestic data; history of food
      ingestion; and results of physical examination, pulse oximetry, gasometry,
      cooximetry, urinalysis, and outcome. Local health authorities provided
      information on nitrate concentration in running water and in vegetables of common
      consumption in the area. RESULTS: The mean age of the patients was 8.14 months
      (range: 7-13). None of the infants was undernourished, had diarrhea, or was given
      any drug. Drinking water showed a nitrate concentration of 3 to 6 ppm. All were
      fed homemade puree of mixed vegetables, prepared in advance and kept in the
      refrigerator for 12 to 27 hours. Silver beets were a common ingredient. No case
      showed metabolic acidosis. Methemoglobin level ranged between 10% and 58%. Three
      cases had nitrituria. Silver beets in our area were the vegetables with the
      highest nitrate concentration (mean: 3200 mg/kg). CONCLUSIONS: Consumption of
      silver beets and incorrect storage of homemade purees of mixed vegetables were
      potential causes of methemoglobinemia in this series. The disease may occur in
      children older than 6 months of age. Nitrituria in a cyanotic infant may suggest
      the diagnosis of methemoglobinemia.methemoglobinemia, nitrates, nitrites, food
      analysis, infant food, food preservation.

PMID- 11331680
TI  - Effect of maternal lead burden on infant weight and weight gain at one month of
      age among breastfed infants.
AB  - INTRODUCTION: Transfer of lead from bone to the bloodstream increases during
      lactation. However, the effect of maternal lead burden on growth in breastfed
      newborns is still unknown. This study examined early postnatal growth in a cohort
      of healthy breastfed newborns in relation to maternal bone lead burden. METHODS:
      Lead levels were measured among 329 mother-infant pairs in umbilical cord blood
      at birth and in maternal and infant venous blood at 1 month postpartum. Maternal
      evaluations at 1 month postpartum included lead measures in blood and bone
      (measured in the tibia and the patella). Blood lead was determined by graphite
      furnace atomic absorption spectrophotometry. Bone lead was measured by (109)Cd Kx
      radiograph fluorescence instrument. The primary endpoints were attained weight 1
      month of age, and weight gain from birth to 1 month of age, which were analyzed
      in relation to lead biomarkers and relevant covariates by linear regression
      models. RESULTS: Infants studied had an average weight gain of 33.1 g/day
      (standard deviation [SD] = 11.6). Mean infant (at 1 month of age) and maternal
      blood lead levels were 5.6 microg/dL (SD = 3.0) and 9.7 microg/dL (SD = 4.1),
      respectively. Mean maternal bone lead levels were 10.1 microg of lead/g (SD =
      10.3) and 15.29 microg of lead/g (SD = 15.2) of bone mineral for tibia and
      patella, respectively. Infant blood lead levels were inversely associated with
      weight gain, with an estimated decline of 15.1 g per microg/dL of blood lead.
      Children who were exclusively breastfed had significantly higher weight gains;
      however, this gain decreased significantly with increasing levels of patella
      lead. The multivariate regression analysis predicted a 3.6-g decrease in weight
      at 1 month of age per microg of lead per gram bone mineral increase in maternal
      patella lead levels. CONCLUSIONS: Maternal lead burden is negatively associated
      to infant attained weight at 1 month of age and to postnatal weight gain from
      birth to 1 month of age. Additional studies are needed to better understand this
      source of exposure and to develop interventions to minimize its impact.

PMID- 11331682
TI  - Examination of state regulations regarding infants and sleep in licensed child
      care centers and family child care settings.
AB  - BACKGROUND: Twenty percent of sudden infant death syndrome (SIDS) occurs in child
      care settings. Although the incidence of SIDS in the United States has decreased
      with increased awareness of the risks of prone infant sleeping, smoke exposure,
      soft bedding, and unsafe sleep environments, avoidance of these risk factors is
      not universally practiced in child care settings. Advocacy through state child
      care regulatory agencies and legislative bodies may be effective in more
      widespread awareness and avoidance of risk factors. OBJECTIVE: To determine what
      individual state regulations for licensed child care centers and family child
      care settings exist regarding: 1) sleep positions for infants under 6 months old,
      2) crib safety, 3) bedding safety, and 4) smoking in the facilities. DESIGN: A
      descriptive survey of regulations for licensed child care centers and family
      child care settings in the 50 states and the District of Columbia. RESULTS:
      Fifteen states use regulations adopted before publication of the first policy
      statement of the American Academy of Pediatrics on infant sleep position and SIDS
      in 1992. Six states require child care centers to place infants nonprone. Sixty
      three percent of states require cribs in child care centers to meet at least 1
      safety standard, and 45.1% require this in family child care homes. Six states
      have provisions limiting the use of soft bedding in child care centers, and 4
      have such bans for family child care homes. Seventy-one percent of states
      prohibit smoking in child care centers during hours of operation; 17% of states
      have similar requirements for family child care homes. CONCLUSIONS: Many states
      use child care regulations that were written before the initial policy statements
      of the American Academy of Pediatrics regarding safe sleep environments for
      infants. Even those more recently adopted regulations do not adequately address
      sleep safety for infants. Pediatricians need to become more proactive in
      promoting safety regulations in child care. Adoption of new regulations can aid
      in education of child care providers and, thus, improve the safety for infants in
      child care.

PMID- 11331683
TI  - Early childhood otitis media in relation to children's attention-related behavior
      in the first six years of life.
AB  - OBJECTIVE: This study examined whether otitis media with effusion (OME) and
      associated hearing loss during the first 4 years of life were related to the
      ratings of parents, teachers, and clinicians of children's attention and behavior
      in the first 6 years of life. METHODS: In a prospective study, 85 black children
      were recruited from community-based child care programs when they were between 6
      and 12 months old. OME and hearing status were monitored repeatedly from 6 months
      to 4 years old. Measures of attention and behavior were collected from parents,
      teachers, and clinicians when the children were infants, preschoolers, and first
      graders. RESULTS: On average, children experienced either bilateral or unilateral
      OME 30% of the time and hearing loss 19.9% of the time between 6 months and 4
      years old. Descriptive and inferential analyses revealed no significant
      associations between OME or hearing loss and the measures of attention or
      behavior completed by parents, teachers, and clinicians. CONCLUSIONS: In this
      sample of children, there was no relationship between amount of early childhood
      OME or hearing loss and measures of attention or behavior in the first 6 years of
      life as reported by parents, teachers, and clinicians.otitis media, hearing,
      attention, behavior.

PMID- 11331684
TI  - Effects of contingent television on physical activity and television viewing in
      obese children.
AB  - OBJECTIVE: Elevated television (TV) viewing and physical inactivity promote
      obesity in children. Thus, changes in physical activity and sedentary behavior
      seem critical to treating childhood obesity. PRESENT STUDY: Using a randomized, 2
      arm design, this pilot study tested the effects of contingent TV on physical
      activity and TV viewing in 10 obese children. TV viewing was contingent on
      pedaling a stationary cycle ergometer for experimental participants but was not
      contingent on pedaling for control participants. The study was conducted over 12
      weeks, including a 2-week baseline period. RESULTS: Multivariate analyses
      indicated that the intervention significantly increased pedaling and reduced TV
      viewing time. During the treatment phase, the experimental group pedaled 64.4
      minutes per week on average, compared with 8.3 minutes by controls. The
      experimental group watched 1.6 hours of TV per week on average, compared with
      21.0 hours per week on average by controls during this phase. Secondary analyses
      indicated that the experimental group showed significantly greater reductions in
      total body fat and percent leg fat. Total pedaling time during intervention
      correlated with greater reductions in percent body fat (r = -0.68). CONCLUSIONS:
      Contingencies in the home environment can be arranged to modify physical activity
      and TV viewing and may have a role in treating childhood obesity. Contingent TV
      may be one method to help achieve this goal.

PMID- 11331685
TI  - The association between childhood depression and adulthood body mass index.
AB  - OBJECTIVE: Stress in childhood relates to both childhood depression and elevated
      adult body mass index (BMI), a measure of relative overweight. However, there are
      limited data on the association between major depression in childhood and BMI in
      adulthood. The current study examines this association. METHOD: Children 6 to 17
      years old with major depression (n = 90) or no psychiatric disorder (n = 87) were
      identified at Columbia Presbyterian Medical Center and followed up 10 to 15 years
      later. Psychiatric status at intake and follow-up was assessed via standardized
      psychiatric interviews. BMI during adulthood was recorded so that the association
      between depression and BMI could be considered over time. RESULTS: Participants
      with childhood major depression had a BMI of 26.1 +/- 5.2 as adults, compared
      with a BMI of 24.2 +/- 4.1 in healthy comparisons (t(175) = 2.7). This
      association could not be explained by a number of potentially confounding
      factors, including age, gender, cigarette or alcohol use, social class, and
      pregnancy or medication history. Although poverty during adulthood also predicted
      adult BMI, both the association between poverty and adult BMI (t(152) = 2.9), as
      well as between childhood depression and adult BMI (t(152) = 2.2) were
      significant in a multivariate model. Finally, duration of depression between
      childhood and adulthood also emerged as a predictor of adult BMI. CONCLUSIONS:
      Depression during childhood is positively associated with BMI during adulthood.
      This association cannot be explained by various potential confounding variables
      and may develop over time as children pass into their adult years.body mass
      index, depression, children, adolescents.

PMID- 11331686
TI  - Developing language skills of cocaine-exposed infants.
AB  - OBJECTIVE: To assess whether there is an association of level of fetal cocaine
      exposure to developmental precursors of speech-language skills at 1 year of age,
      after controlling for confounding factors. DESIGN: In a prospective,
      longitudinal, quasi-experimental, matched cohort design, 3 cocaine exposure
      groups were defined by maternal self-report and infant meconium assay:
      nonexposure (n = 131), heavier exposure (n = 66), >the 75th percentile for
      maternal self-report and >the 70th percentile of benzoylecgonine concentration,
      and all others as lighter exposure (n = 68). At 1 year of age, the Preschool
      Language Scale-3 was administered by examiners unaware of infant drug status.
      RESULTS: Independent of confounding drug, medical, and environmental factors,
      more heavily exposed infants had lower auditory comprehension scores than
      nonexposed infants and lower total language scores than lighter and nonexposed
      infants. More heavily exposed infants were also more likely to be classified as
      mildly delayed by total language score than nonexposed infants. There were
      positive linear relationships between the concentration of benzoylecgonine in
      meconium and all outcomes and between maternal report of severity of prenatal
      cocaine use with poorer auditory comprehension indicating a relationship between
      amount of exposure and poorer outcomes. CONCLUSIONS: This study documents
      significant behavioral teratogenic effects of fetal cocaine exposure on
      attentional abilities underlying auditory comprehension skills considered to be
      precursors of receptive language. Pediatricians are in a unique position to
      monitor early development of cocaine-exposed infants and make timely referrals
      for intervention.

PMID- 11331687
TI  - The effect of late doses on the achievement of seroprotection and antibody titer
      levels with hepatitis b immunization among adolescents.
AB  - OBJECTIVE: To determine the effect of varying dosing schedules and predictor
      variables on the seroprotection rates and geometric mean titer levels resulting
      from the hepatitis B vaccination series among adolescents. METHODS: Adolescents
      received the hepatitis B vaccination series at varying schedules according to
      their natural adherence patterns. Data collected included participants'
      medication use; chronic illness; use of cigarettes, alcohol, and marijuana; age;
      race/ethnicity; and body mass index. Participants' dates of vaccinations were
      recorded and titer levels for hepatitis B surface antibody were drawn ~12 and 24
      months after study enrollment. The data for 498 participants were analyzed using
      chi(2) tests, Student t tests, logistic regression models, and analysis of
      variance. RESULTS: Seroprotection rates among adolescents were not affected by
      late vaccinations. The only factors affecting the achievement of seroprotection
      ~12 and 24 months after the first vaccination were body mass index and the number
      of immunizations received. Increased time between doses 1 and 2 and doses 2 and 3
      showed a trend toward correlating with increasing titer levels. CONCLUSIONS:
      Although adolescents at risk of acquiring hepatitis B should receive the
      hepatitis B vaccination series in a timely fashion, late doses are not
      detrimental, and may be beneficial, to achieving high antibody levels against the
      hepatitis B virus.

PMID- 11331688
TI  - Cardiovascular effects of hydrocortisone in preterm infants with pressor
      resistant hypotension.
AB  - OBJECTIVE: To study the cardiovascular effects of hydrocortisone in preterm
      infants with hypotension unresponsive to volume and pressor administration. STUDY
      DESIGN: Retrospective review of the cardiovascular response to 23 courses of
      hydrocortisone administration during the first day of treatment in 21 preterm
      infants (gestational age: 26.9 +/- 3.9 weeks; postnatal age: 11.3 +/- 13.1 days).
      Hydrocortisone (2 mg/kg/d in 16 patients and 3-6 mg/kg/d in 5 patients) was
      administered when dopamine (22.2 +/- 11 microg/kg/min, range: 8-60) alone (n =
      16) or in combination with dobutamine (8.4 +/- 4.9 microg/kg/min, range: 5-20, n
      = 7) and/or epinephrine (0.38 +/- 0.56 microg/kg/min, range: 0.01-1.2, n = 4)
      failed to normalize blood pressure. RESULTS: Mean blood pressure increased from
      29.3 +/- 4.1 to 34.1 +/- 5.2, 38.0 +/- 8.0, and 41.8 +/- 6.6 mm Hg by 2, 4, and 6
      hours of hydrocortisone administration, respectively, and remained stable
      thereafter. Urine output increased despite a decrease in fluid administration
      during the first day of hydrocortisone treatment. The dose of dopamine and the
      number of patients receiving dobutamine and/or epinephrine also decreased during
      the same period. Eighteen of the 21 patients survived. CONCLUSIONS: Preterm
      infants with volume- and pressor-resistant hypotension respond to hydrocortisone
      with rapid normalization of the cardiovascular status and sustained decreases in
      volume and pressor requirement.

PMID- 11331689
TI  - Developmental follow-up of breastfed term and near-term infants with marked
      hyperbilirubinemia.
AB  - OBJECTIVE: In recent years, the increased prevalence of breastfeeding in
      conjunction with early discharge practices has increased the risk for marked
      hyperbilirubinemia in neonates. This has resulted in the potential for bilirubin
      brain injury in affected infants. The purpose of this study was to identify all
      infants >/=36 weeks' gestational age with bilirubin levels >25 mg/dL and evaluate
      them for early and late evidence of bilirubin brain injury. METHODS: We reviewed
      the charts of all infants (from 1993-1996) >/=36 weeks' gestational age who were
      readmitted to the hospital during the first week of life with bilirubin levels
      >25 mg/dL. Readmission records were reviewed for early signs of bilirubin
      encephalopathy. Magnetic resonance imaging (MRIs) and Brainstem auditory-evoked
      responses (BAERs) were reviewed for evidence of bilirubin toxicity. At follow-up,
      study infants had a complete neurodevelopmental examination, repeat MRIs, and
      behavioral hearing evaluations. RESULTS: From 1993 to 1996, we identified 6 term
      and near-term infants readmitted to the hospital within the first week of life
      with peak bilirubin values ranging from 26.4 mg/dL (451 micromol/L) to 36.9 mg/dL
      (631 micromol/L). Five of 6 infants had bilirubin values >30 mg/dL (513
      micromol/L). All were exclusively breastfed or fed a combination of breast and
      bottle feedings. Five of 6 infants presented with abnormal neurologic signs. Four
      infants had initial MRIs, 3 of whom had increased signal intensity in the basal
      ganglia consistent with kernicterus. Two infants had abnormal BAERs; both also
      had abnormal MRIs. Five of 6 infants received exchange transfusions and all were
      treated with phototherapy and intravenous fluids. Follow-up examinations between
      3 months and 2 years showed resolution of clinical signs in all but 1 infant.
      Four infants had a subsequent normal MRI and 1 had residual hearing impairment.
      One infant demonstrated severely abnormal developmental evaluations, as well as
      both an abnormal initial MRI and BAERs. Follow-up MRI showed evidence of
      encephalomalacia with changes not characteristic of kernicterus. CONCLUSIONS: We
      observed transient neurologic abnormalities in 5 of 6 infants readmitted to the
      hospital during the first week of life with marked hyperbilirubinemia. The
      abnormalities resolved following aggressive management using hydration,
      phototherapy, and exchange transfusion and may not correlate with long-term
      prognosis. Less aggressive therapy may be associated with residual neurologic
      abnormalities. We speculate that inadequate establishment of breastfeeding
      coupled with early discharge practices may play a role in the development of
      marked hyperbilirubinemia in these infants.

PMID- 11331690
TI  - High-flow nasal cannulae in the management of apnea of prematurity: a comparison
      with conventional nasal continuous positive airway pressure.
AB  - Apnea of prematurity (AOP) is frequently managed with nasal continuous positive
      airway pressure (NCPAP). Nasal cannula (NC) are used at low flows (<0.5 L/min) to
      deliver supplemental oxygen to neonates. A number of centers use high-flow nasal
      cannula (HFNC) in the management of AOP without measuring the positive distending
      pressure (PDP) generated. Objective. To determine the NC flow required to
      generate PDP equal to that provided by NCPAP at 6 cm H(2)O and to assess the
      effectiveness of HFNC as compared NCPAP in the management of AOP. Method. Forty
      premature infants, gestation 28.7 +/- 0.4 weeks (mean +/- standard error of
      mean), postconceptual age at study 30.3 +/- 0.6 weeks, birth weight 1256 +/- 66
      g, study weight 1260 +/- 63 g who were being managed with conventional NCPAP for
      at least 24 hours for clinically significant apnea of prematurity, were enrolled
      in a trial of ventilator-generated conventional NCPAP versus infant NC at flows
      of up to 2.5 L/min. End expiratory esophageal pressure was measured on NCPAP and
      on NC, and the gas flow on NC was adjusted to generate an end expiratory
      esophageal pressure equal to that measured on NCPAP. Two 6-hour periods were
      continuously recorded and the data were stored on computer. Results. The flow
      required to generate a comparable PDP with NC varied with the infant's weight and
      was represented by the equation: flow (L/min) = 0.92 + 0.68x, x = weight in kg, R
      = 0.72. There was no difference in the frequency and duration of apnea,
      bradycardia or desaturation per recording between the 2 systems. Conclusion. NC
      at flows of 1 to 2.5 L/min can deliver PDP in premature neonates. HFNC is as
      effective as NCPAP in the management of AOP.

PMID- 11331691
TI  - Assessing health system provision of well-child care: The Promoting Healthy
      Development Survey.
AB  - BACKGROUND: Preventive care guidelines for children include parent education and
      counseling, developmental assessment, and screening for psychosocial and safety
      risks. Health care providers are in a unique position to identify and follow up
      on potential problems and to influence parenting knowledge, attitudes, and
      behavior to ensure the healthy development of young children. Few quality
      measures are available to assess health care system performance in this important
      area. OBJECTIVE: To develop a feasible, valid, and reliable methodology for
      evaluating health care system performance in providing family-centered
      anticipatory guidance and child and family assessment services on behalf of
      children from birth through 48 months old. Methods. The Promoting Healthy
      Development Survey (PHDS) was developed and tested with a diverse group of
      families in 3 managed care organizations (n = 1478). A standard mail
      administration protocol was used, including an informed consent with a waiver of
      documentation, 2 mailings, a postcard reminder, and telephone reminders. The 36
      item parent survey assesses whether health care providers(1) talk with parents
      about topics recommended in Bright Futures and the American Academy of Pediatrics
      Guidelines for Health Supervision,(2) provide follow-up for children who may be
      at risk for developmental problems,(3) and address psychosocial well-being and
      safety within the family. The PHDS also assesses the degree to which parent's
      interactions with providers are family-centered, helpful, and facilitate parental
      confidence. Psychometric, bivariate, and multivariate analyses were conducted to
      assess the reliability, validity, and patterns of variation in the seven quality
      measures derived from the PHDS. RESULTS: Psychometric analyses demonstrated that
      the PHDS quality measure scales have strong construct validity (mean factor
      loading: 0.69) and internal consistency (mean Cronbach's alpha: 0.80). Parents
      reporting positive parenting behaviors had significantly higher scores on the
      anticipatory guidance quality measure compared with parents not reporting
      positive behaviors. Parents who reported that their questions on specific
      anticipatory guidance topics were answered were more likely to report higher
      confidence in related parenting activities (odds ratio [OR]: 5.9, 95% confidence
      interval [CI]: 3.4-10.2; OR: 8.3, 95% CI: 5-13.8)and were less likely to report
      concerns about their child's development in related areas compared with parents
      who reported they wished they had talked more with their child's doctor about
      these topics (OR: 0.46, 95% CI: 0.29-0.72; OR: 0.58, 95% CI: 0.37-0.89). The 7
      PHDS quality measure scores for health plans ranged from 17 to 67 (on a 0-100
      scale; where 100 is the best score possible) and varied significantly across
      health plans. Performance was highest for provision of anticipatory guidance
      information from health plans and lowest for family psychosocial assessment.
      Scores for families with Medicaid coverage were significantly higher on 2 of the
      PHDS measures and significantly lower for 3 measures compared with scores for
      families with commercial insurance. Age of child, whether child is first- born,
      parental marital status, education, income, and race were significant predictors
      for 1 or more of the PHDS quality measures (average R(2) = 0.05). CONCLUSIONS:
      The PHDS provides a comprehensive, psychometrically valid and reliable assessment
      of how well health plans and the health care providers working within these plans
      promote the healthy development of young children. The PHDS seems to
      differentiate among health care plans and among the different aspects of
      preventive care provided within a health plan. For the population studied here,
      there is significant room for improvement in ensuring families and children
      receive appropriate and family-centered care to promote the healthy development
      of children between 3 and 48 months old. Because the PHDS is conceptually based
      on national recommendations for child health supervision, improved performance on
      the PHDS would indicate greater adherence to these national recommendations and
      progress toward the achievement of Healthy People 2010 goals. The
      generalizability of the findings presented in this report are being examined
      using data collected in 5 statewide Medicaid samples (N = 11 696) and data from
      the National Survey of Early Childhood Health, which has incorporated most of the
      PHDS items.

PMID- 11331692
TI  - Noninvasive assessment of the early progression of atherosclerosis in adolescents
      with Kawasaki disease and coronary artery lesions.
AB  - OBJECTIVES: The severity of carotid arteriosclerosis, defined as increased intima
      media thickness (IMT) visible with B-mode ultrasound, is correlated with risk
      factors for coronary heart disease. Little is known, however, about the relation
      of IMT, the stiffness of the common carotid artery, and the progression of
      atherosclerosis in children with Kawasaki disease (KD) and coronary artery
      lesions (CAL). DESIGN: We investigated the associations among total cholesterol
      (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein
      cholesterol (LDL-C), triglyceride, TC/HDL-C, ApoE genotype, glycohemoglobin, IMT,
      and arterial stiffness by high resolution ultrasound in 20 adolescents with KD
      and CAL (age: 16.6 +/- 4.1 years, males: 60%) and 20 sex- and age-matched healthy
      controls (Cont). RESULTS: No significant differences were observed in the values
      of body mass index and blood pressure between the 2 groups. Also no significant
      differences were observed in the levels of TC, LDL-C, HDL-C, triglyceride, TC/HDL
      C within normal values, or the allele frequency of Apo E4 between the 2 groups.
      However, the values of IMT, stiffness, and glycohemoglobin in patients with KD
      were significantly higher than those in Cont (0.53 +/- 0.07 vs 0.46 +/- 0.05 mm,
      P <.05; 4.11 +/- 0.86 vs 2.94 +/- 0.91, P <.001; 5.0 +/- 0.4 vs 4.6 +/- 0.2%, P
      <.05). A significant relationship was observed between sex and the mean IMT (r =
      0.46) in Cont; however, no significant correlation was found between mean IMT and
      other variables in either group. Although the arterial stiffness was strongly
      related to body mass index (r = 0.58) and systolic blood pressure (r = 0.55) in
      Cont, no significant relationship was observed between the stiffness and any
      variable tested in patients with KD. CONCLUSIONS: The less distensible carotid
      wall in patients with KD compared with that in Cont without major alteration of
      the lipid profile is likely to be secondary to the changes in arterial walls
      after a diffuse vasculitis involving noncoronary arteries. These results indicate
      that the coronary arteries may be predisposed to accelerated atherosclerosis in
      patients with KD and CAL.

PMID- 11331693
TI  - Improving the delivery of adolescent clinical preventive services through skills
      based training.
AB  - OBJECTIVE: To examine the efficacy of skills-based training workshops on primary
      care providers' screening and counseling practices with adolescents during
      routine outpatient well visits. DESIGN: Sixty-three primary care providers in
      outpatient pediatric departments within a managed health care organization
      participated in two 4-hour workshops on clinical preventive services for
      adolescents. The workshops focused on adolescent health, confidentiality,
      screening, and anticipatory guidance/brief counseling for 5 risk behaviors
      including: helmet and seatbelt use, tobacco use, alcohol use, and sexual
      behavior. A pre/posttest design was used to assess clinicians' screening and
      counseling practices during the pretraining and posttraining periods. Independent
      adolescent reports of clinicians' practices were obtained from 2 samples of 14-
      to 16-year-old adolescents immediately after their routine well visit in the
      outpatient clinics. One sample of adolescents reported during a pretraining
      period and a separate sample reported during a period after the training.
      RESULTS: Adolescent reports indicated that after the training workshops, the
      average percentage of adolescents screened by their primary care providers
      increased significantly for seatbelt use (from mean 38% to 56%), helmet use (from
      mean 27% to 45%), tobacco use (from mean 64% to 76%), alcohol use (from mean 59%
      to 76%), and sexual behavior (from mean 61% to 75%). Additionally, the average
      percentage of adolescents offered brief counseling by their clinicians increased
      significantly after training in the areas of seatbelt use (from mean 36% to 51%),
      helmet use (from mean 25% to 43%), and sexual behavior (from mean 42% to 58%).
      Improvement after the training in brief counseling for tobacco use was marginally
      significant (from mean 60% to 69%) and for alcohol use was not significant,
      although there was an increase. Clinicians also significantly increased their
      discussion of the limits of confidentiality with their adolescent patients after
      the training workshops (from mean 32% to 45%). CONCLUSIONS: This study offers
      strong support for the efficacy of skills-based training for primary care
      providers as a method for increasing screening and counseling practices with
      adolescents. The present findings suggest that with appropriate skills-based
      training, practicing clinicians can implement several of the national guidelines
      that direct them to provide preventive services for multiple behaviors in a
      routine outpatient visit. Screening and counseling in these visits are important
      in the early identification, detection, and prevention of behaviors associated
      with the primary adolescent morbidities and mortalities. Thus, enhancing the
      delivery of clinical preventive services is an important step in the prevention
      of untoward health outcomes for youth.

PMID- 11331694
TI  - Invasive group A streptococcal infection and nonsteroidal antiinflammatory drug
      use among children with primary varicella.
AB  - OBJECTIONS: To test the hypothesis that nonsteroidal antiinflammatory drug use
      increases the risk of necrotizing soft tissue infections and, secondarily, all
      invasive group A streptococcal (GAS) infections in children with primary
      varicella infection. METHODS: We conducted a prospective, multicenter case
      control study among children <19 years old. Cases were children hospitalized with
      primary varicella complicated by invasive GAS infection or necrotizing soft
      tissue infection identified by a network of 45 pediatric infectious disease
      specialists located throughout the United States. Controls were children with
      uncomplicated primary varicella residing in the same communities as the cases.
      Data on medical history, clinical features of the varicella infection, signs and
      symptoms of infectious complications, and medication use were collected by
      structured telephone interviews. Univariate and multivariate matched odds ratios
      were calculated using conditional logistic regression. RESULTS: Between June 1996
      and September 1998, 52 cases of invasive GAS infection, including 21 with
      necrotizing soft tissue infection, and 172 controls with uncomplicated primary
      varicella were enrolled. Risk of invasive GAS infection was increased among
      children who were nonwhite (multivariate odds ratio [OR] 3.8, 95% confidence
      interval [CI]: 1.4-11), living in low-income households (OR 5.1, 95% CI: 1.7-15),
      exposed to varicella at home (OR 6.4, 95% CI: 2.6-16), or had a persistent high
      fever (OR 9.6, 95% CI: 2.8-33). Antipyretic regimen was associated with several
      measures of varicella illness severity among the controls. The risk of
      necrotizing soft tissue infection was not associated with the use of ibuprofen
      before the development of signs or symptoms of this complication (OR 1.3, 95% CI:
      0.33-5.3). Risk of any invasive GAS infection was increased among children who
      had received ibuprofen (OR 3.9, 95% CI: 1.3-12), but not acetaminophen (OR 1.2,
      95% CI: 0.50-3.0). However, there was no evidence of increasing risk with
      increasing duration of ibuprofen use. Subgroup analyses revealed that the risk of
      invasive GAS infection was increased only among children who had received both
      acetaminophen and ibuprofen. CONCLUSIONS: These data do not support the
      hypothesis that nonsteroidal antiinflammatory drugs, or ibuprofen in particular,
      increase the risk of necrotizing GAS infections. A statistically significant
      association was observed between nonnecrotizing invasive GAS infection and
      ibuprofen use; however, because of potential confounding, the meaning of this
      unexpected result is unclear. Nonetheless, these data suggest that parents use
      ibuprofen or ibuprofen together with acetaminophen to treat high fever and severe
      illness, which seems to identify children at high risk for invasive GAS
      infection.

PMID- 11331695
TI  - Exposure to X-rated movies and adolescents' sexual and contraceptive-related
      attitudes and behaviors.
AB  - OBJECTIVES: To examine the association between exposure to X-rated movies and
      teens' contraceptive attitudes and behaviors. METHODS: Black females, 14 to 18
      years old (n = 522) were recruited from adolescent medicine clinics, health
      departments, and school health clinics. RESULTS: Exposure to X-rated movies was
      reported by 29.7% of adolescents. Exposure to X-rated movies was associated with
      being more likely to have negative attitudes toward using condoms (odds ratio
      [OR]: 1.4), to have multiple sex partners (OR: 2.0), to have sex more frequently
      (OR: 1.8), to not have not used contraception during the last intercourse (OR:
      1.5), to have not used contraception in the past 6 months (OR: 2.2), to have a
      strong desire to conceive (OR: 2.3), and to test positive for chlamydia (OR:
      1.7). CONCLUSIONS: Additional research is needed to understand the impact of X
      rated movies on adolescents' sexual and contraceptive health.

PMID- 11331697
TI  - Attitudes of New York City high school students regarding firearm violence.
AB  - OBJECTIVES: To assess prevalence of gun possession, attitudes regarding gun
      possession and gun violence, knowledge and influences of gun violence, and the
      potential role of physicians in gun violence prevention education among
      adolescents. METHODS: An anonymous questionnaire was distributed to 9th through
      12th grade high school students at 3 public high schools in New York City.
      RESULTS: Three hundred forty-two surveys were distributed and returned. The
      prevalence of guns in the homes was 19.6%. Of respondents, 43.2% thought it was
      okay for anyone to have guns, and 57.3% had been injured or have had a relative
      injured by a gun. Although 11.6% of adolescents had felt the need to talk to an
      adult about guns, only 3.0% listed their physicians as one of these adults.
      However, if asked by their physician, 63.8% would discuss the issue with them.
      Only 5.7% of adolescents have had a physician speak to them about guns.
      CONCLUSIONS: The adolescent population surveyed is frequently exposed to gun
      violence. Although physicians rarely counsel adolescents regarding gun violence
      and firearm safety, many adolescents would be receptive to this mode of
      intervention.adolescence, attitude, firearm ownership, firearm violence,
      physician role.

PMID- 11331696
TI  - Closed-loop controlled inspired oxygen concentration for mechanically ventilated
      very low birth weight infants with frequent episodes of hypoxemia.
AB  - BACKGROUND: Mechanically ventilated very low birth weight infants often present
      with frequent episodes of hypoxemia, and maintaining arterial oxygen saturation
      by pulse oximetry (SpO(2)) within a normal range by manual fraction of inspired
      oxygen (FIO(2)) adjustments is difficult and time consuming. OBJECTIVES: An
      algorithm for closed-loop FIO(2) control (cFIO(2)) to maintain SpO(2) within a
      target range was compared with continuous manual FIO(2) (mFIO(2)) adjustments by
      a nurse in a group of ventilated infants who presented with frequent episodes of
      hypoxemia. RESULTS: Fourteen infants (birth weight: 712 +/- 142 g; gestational
      age: 25 +/- 1.6 weeks; age: 26 +/- 11 days; synchronized intermittent mandatory
      ventilation rate: 24 +/- 10 b/m; peak inspiratory pressure: 17.5 +/- 2.0 cmH(2)O;
      positive end-expiratory pressure: 4.3 +/- 0.5 cmH(2)O) were studied for 2 hours
      on each mode in random sequence. Both modes aimed to maintain SpO(2) between 88%
      and 96%. There were 15 +/- 7 and 16 +/- 6 hypoxemic episodes/hour (SpO(2) <88%,
      >5 s) during mFIO(2) and cFIO(2), respectively; episode duration was 41 +/- 23
      and 32 +/- 15 s, totaling 19 +/- 16% and 17 +/- 12% of recording time. There were
      13 +/- 10 and 10 +/- 8 hyperoxemic episodes/hour (SpO(2)>96%, >5 s) during
      mFIO(2) and cFIO(2,) respectively; episode duration was 27 +/- 15 and 24 +/- 19
      s, totaling 15 +/- 14% and 10 +/- 9% of recording time. Mean SpO(2) and FIO(2)
      levels were similar during both modes. The nurse made 29 +/- 17 adjustments/hour
      during mFIO(2). There was a significant increase in the duration of normoxemia
      (SpO(2) between 88%-96%) during cFIO(2) (75 +/- 13 vs 66 +/- 14% of recording
      time). CONCLUSION: In this group of infants, cFIO(2) was at least as effective as
      a fully dedicated nurse in maintaining SpO(2) within the target range, and it may
      be more effective than a nurse working under routine conditions. We speculate
      that during long-term use, cFIO(2) may save nursing time and reduce the risks of
      morbidity associated with supplemental oxygen and episodes of hypo- and
      hyperoxemia.

PMID- 11331698
TI  - Detecting suicide risk in a pediatric emergency department: development of a
      brief screening tool.
AB  - OBJECTIVE: To develop a brief screening tool that will allow emergency department
      (ED) staff to rapidly and accurately detect suicide risk in child and adolescent
      patients. DESIGN: Cross-sectional survey. Participants. One hundred forty-four
      children and adolescents, mean age of 13.6 years, presenting to an urban
      university teaching hospital pediatric ED for primarily psychiatric reasons. Data
      Collection. As part of a quality improvement initiative, we developed a 14-item
      screening survey (the Risk of Suicide Questionnaire [RSQ]) that was administered
      by a triage nurse to all pediatric mental health patients on admission to the ED.
      All patients were subsequently administered the 30-item Suicide Ideation
      Questionnaire (SIQ) by a mental health clinician, which served as the criterion
      standard assessment of suicidality. Other information collected included
      demographic and clinical characteristics. MAIN OUTCOME MEASURES: Sensitivity,
      specificity, positive predictive value, negative predictive value (NPV), and area
      under the receiver operating characteristic curve for responses to individual and
      combinations of RSQ items, relative to determinations of suicidality by the
      criterion standard SIQ. RESULTS: Four of the items from the RSQ had a predictive
      c statistic of 0.87, a sensitivity of 0.98, and a NPV of 0.97. Little improvement
      in predictive ability was obtained by including other RSQ items (c statistic for
      the most predictive 4-item model = 0.87; c statistic for the model containing all
      14 items = 0.90). Among all possible combinations of 4 RSQ items, the combination
      of items inquiring about current suicidal behavior, past suicidal ideation, past
      self-destructive behavior, and current stressors yielded the highest sensitivity
      (0.98), NPV (0.97), and c statistic (0.87), as assessed by the criterion standard
      SIQ. CONCLUSIONS: A brief 4-item screening tool can be used by nonmental health
      clinicians to accurately detect suicidality in children and adolescents who visit
      an ED. Early and accurate identification of suicidality is a critical first step
      that could lead to better treatment and improved health outcomes for children and
      adolescents with mental health concerns.

PMID- 11331699
TI  - Why don't low-income mothers worry about their preschoolers being overweight?
AB  - CONTEXT: Mothers are in an important position to prevent obesity in their
      children by shaping early diet and activity patterns. However, many mothers of
      overweight preschool children are not worried about their child's weight.
      OBJECTIVE: To explore mothers' perceptions about how they determine when a child
      is overweight, why children become overweight, and what barriers exist to
      preventing or managing childhood obesity. DESIGN: Three focus groups with 6
      participants in each. Participant comments were transcribed and analyzed. Themes
      were coded independently by the 6 authors who then agreed on common themes.
      SETTING: A clinic of the Special Supplemental Nutrition Program for Women,
      Infants, and Children in Cincinnati, Ohio. PARTICIPANTS: Eighteen low-income
      mothers (13 black, 5 white) of preschool children (mean age of 44 months) who
      were at-risk for later obesity. All but 1 mother had a body mass index (BMI)
      >/=25 kg/m(2), and 12 mothers had a BMI >/=30 kg/m(2). All but 1 child had a BMI
      >/=85th percentile for age and sex, and 7 had a BMI >/=95th percentile. Results.
      Mothers did not define overweight or obese in their children according to how
      height and weight measurements were plotted on the standard growth charts used by
      health professionals. Instead, mothers were more likely to consider being teased
      about weight or developing limitations in physical activity as indicators of
      their child being overweight. Children were not believed to be overweight if they
      were active and had a healthy diet and/or a good appetite. Mothers described
      overweight children as thick or solid. Mothers believed that an inherited
      tendency to be overweight was likely to be expressed in the child regardless of
      environmental factors. In trying to shape their children's eating, mothers
      believed that their control over the child's diet was challenged by other family
      members. If a child was hungry, despite having just eaten, it was emotionally
      difficult for mothers to deny additional food. CONCLUSIONS: Health professionals
      should not assume that defining overweight according to the growth charts has
      meaning for all mothers. Despite differing perceptions between mothers and health
      professionals about the definition of overweight, both groups agree that children
      should be physically active and have healthy diets. Health professionals may be
      more effective in preventing childhood obesity by focusing on these goals that
      they share with mothers, rather than on labeling children as overweight.

PMID- 11331700
TI  - An assessment of thimerosal use in childhood vaccines.
AB  - BACKGROUND: On July 7, 1999, the American Academy of Pediatrics and the US Public
      Health Service issued a joint statement calling for removal of thimerosal, a
      mercury-containing preservative, from vaccines. This action was prompted in part
      by a risk assessment from the Food and Drug Administration that is presented
      here. METHODS: The risk assessment consisted of hazard identification, dose
      response assessment, exposure assessment, and risk characterization. The
      literature was reviewed to identify known toxicity of thimerosal, ethylmercury (a
      metabolite of thimerosal) and methylmercury (a similar organic mercury compound)
      and to determine the doses at which toxicity occurs. Maximal potential exposure
      to mercury from vaccines was calculated for children at 6 months old and 2 years,
      under the US childhood immunization schedule, and compared with the limits for
      mercury exposure developed by the Environmental Protection Agency (EPA), the
      Agency for Toxic Substance and Disease Registry, the Food and Drug
      Administration, and the World Health Organization. RESULTS: Delayed-type
      hypersensitivity reactions from thimerosal exposure are well-recognized.
      Identified acute toxicity from inadvertent high-dose exposure to thimerosal
      includes neurotoxicity and nephrotoxicity. Limited data on toxicity from low-dose
      exposures to ethylmercury are available, but toxicity may be similar to that of
      methylmercury. Chronic, low-dose methylmercury exposure may cause subtle
      neurologic abnormalities. Depending on the immunization schedule, vaccine
      formulation, and infant weight, cumulative exposure of infants to mercury from
      thimerosal during the first 6 months of life may exceed EPA guidelines.
      CONCLUSION: Our review revealed no evidence of harm caused by doses of thimerosal
      in vaccines, except for local hypersensitivity reactions. However, some infants
      may be exposed to cumulative levels of mercury during the first 6 months of life
      that exceed EPA recommendations. Exposure of infants to mercury in vaccines can
      be reduced or eliminated by using products formulated without thimerosal as a
      preservative.

PMID- 11331701
TI  - Role of the pediatrician in family-centered early intervention services.
AB  - There is growing evidence that early intervention services have had a positive
      influence on the developmental outcome of children with established disabilities
      or those considered "at risk" for disabilities and their families. Various
      federal and state statutes now mandate that community-based, coordinated,
      multidisciplinary, family-centered programs be established, which are accessible
      to serve children and families in need. The pediatrician, in close collaboration
      with the family and the early intervention team, plays a critical role in guiding
      the clinical and developmental aspects of the early intervention services
      provided. This role can be best served in the context of providing a medical home
      for children with special health care needs. The purpose of this statement is to
      assist the pediatrician in assuming a proactive role on the multidisciplinary
      team providing early intervention services.

PMID- 11331702
TI  - Ethics and immunization policy: promoting dialogue to sustain consensus.
AB  - The societal consensus that has supported the United States' universal childhood
      immunization programs for the past 50 years shows signs of eroding. This article
      proposes a systematic approach to evaluate immunization policy options. Through a
      unifying framework that combines epidemiologic, economic, and ethical concerns,
      this approach promotes a clearer understanding of underlying issues and inherent
      tradeoffs between alternative policies. Such a systematic examination of policy
      options could facilitate the public dialogue necessary to continually recreate a
      broad consensus on immunization practices and enable us to choose policies most
      in accord with our fundamental values.

PMID- 11331703
TI  - Management of otitis media and functional outcomes related to language, behavior,
      and attention: is it time to change our approach?

PMID- 11331704
TI  - What happened to primum non nocere?

PMID- 11331705
TI  - The future of pediatric education (FOPE) II report summary and pediatric
      subspecialists.

PMID- 11331706
TI  - A family cluster of streptococcal toxic shock syndrome in children: clinical
      implication and epidemiological investigation.
AB  - BACKGROUND: Most invasive group A streptococcal (GAS) disease occurs
      sporadically. Reports of family clusters of these infections are scanty, and most
      invasive disease occurs in adults. We describe a family cluster of streptococcal
      toxic shock syndrome (STSS) involving 3 children and present the results of an
      epidemiologic investigation. PATIENTS AND METHODS: During a 16-day period, 3
      children in a family developed STSS with an interval of 7 and 9 days,
      respectively, between the onset of disease. Cases 2 and 3 had GAS isolated from
      blood culture. Case 2 was fatal. Pharyngeal culture survey of the family members
      and schoolchildren was conducted. Antibiogram, serotyping, detection of exotoxin
      genes, and random amplified polymorphic DNA patterns of the disease strains and
      survey strains were examined. RESULTS: One of 15 family members sampled-the
      sister of the index case-and 7 (5.6%) of 125 schoolchildren sampled had GAS
      isolated from pharyngeal cultures. Of the 10 strains examined, 2 isolates from
      the patients, 1 from the sister of index case, and 2 from the classmates of case
      2 (the fatal case) had an identical pattern of both genotype and phenotype.
      CONCLUSION: We describe a family cluster of STSS involving 3 children caused by a
      single clone and provide additional data regarding invasive GAS infection
      subsequent to household contact. Additional studies should be conducted in
      conjunction with surveillance to define better the magnitude of risk in household
      contacts and to identify settings in which subsequent infections may occur.

PMID- 11331707
TI  - Glutaric acidemia, type I, missed by newborn screening in an infant with dystonia
      following promethazine administration.
AB  - We report a child initially diagnosed with promethazine-induced dystonia despite
      a lack of response to diphenhydramine therapy. On further evaluation, the child
      was diagnosed with glutaric acidemia, type I (GA-I), an autosomal recessive
      inborn error of metabolism caused by the deficiency of glutaryl-CoA
      dehydrogenase. The characteristic clinical feature of GA-I is an acute
      encephalopathic and neurologic crisis typically occurring during a catabolic
      state. Despite slow improvement, many patients do not fully recover from a
      neurologic crisis, and residual neurologic morbidity can be significant. Although
      newborn screening using tandem mass spectrometry is expected to enable
      presymptomatic diagnosis of GA-I, this patient was not detected by newborn
      screening with tandem mass spectrometry. Therefore, a high suspicion of GA-I must
      be maintained in the evaluation of childhood dystonia, even when newborn
      screening results are reportedly normal.

PMID- 11331708
TI  - American Academy of Pediatrics: Falls from heights: windows, roofs, and
      balconies.
AB  - Falls of all kinds represent an important cause of child injury and death. In the
      United States, approximately 140 deaths from falls occur annually in children
      younger than 15 years. Three million children require emergency department care
      for fall-related injuries. This policy statement examines the epidemiology of
      falls from heights and recommends preventive strategies for pediatricians and
      other child health care professionals. Such strategies involve parent counseling,
      community programs, building code changes, legislation, and environmental
      modification, such as the installation of window guards and balcony railings.

PMID- 11331709
TI  - American Academy of Pediatrics: Health care supervision for children with
      Williams syndrome.
AB  - This set of guidelines is designed to assist the pediatrician to care for
      children with Williams syndrome diagnosed by clinical features and with regional
      chromosomal microdeletion confirmed by fluorescence in situ hybridization.

PMID- 11331710
TI  - American Academy of Pediatrics: Medical conditions affecting sports
      participation.
AB  - Children and adolescents with medical conditions present special issues with
      respect to participation in athletic activities. The pediatrician can play an
      important role in determining whether a child with a health condition should
      participate in certain sports by assessing the child's health status, suggesting
      appropriate equipment or modifications of sports to decrease the risk of injury,
      and educating the athlete and parents on the risks of injury as they relate to
      the child's condition. This statement updates a previous policy statement and
      provides information for pediatricians on sports participation for children and
      adolescents with medical conditions.

PMID- 11331711
TI  - American Academy of Pediatrics: The use and misuse of fruit juice in pediatrics.
AB  - Historically, fruit juice was recommended by pediatricians as a source of vitamin
      C and an extra source of water for healthy infants and young children as their
      diets expanded to include solid foods with higher renal solute. Fruit juice is
      marketed as a healthy, natural source of vitamins and, in some instances,
      calcium. Because juice tastes good, children readily accept it. Although juice
      consumption has some benefits, it also has potential detrimental effects.
      Pediatricians need to be knowledgeable about juice to inform parents and patients
      on its appropriate uses.

PMID- 11331712
TI  - American Academy of Pediatrics: Implementation principles and strategies for the
      State Children's Health Insurance Program.
AB  - This policy statement presents principles and implementation and evaluation
      strategies recommended for the State Children's Health Insurance Program (SCHIP).
      The statement summarizes the current status of SCHIP, the needs of uninsured
      children, and the potential benefits of SCHIP programs. Principles and
      recommended strategies include expanding eligibility, maximizing funding,
      providing comprehensive benefits, including pediatricians in program design and
      evaluation, providing adequate reimbursement and access to pediatricians,
      ensuring choices for families and pediatricians, and establishing simple
      administrative procedures.

PMID- 11331713
TI  - American Academy of Pediatrics: The pediatrician's role in the diagnosis and
      management of autistic spectrum disorder in children.
AB  - Primary care physicians have the opportunity, especially within the context of
      the medical home, to be the first point of contact when parents have concerns
      about their child's development or behavior. The goal of this policy statement is
      to help the pediatrician recognize the early symptoms of autism and participate
      in its diagnosis and management. This statement and the accompanying technical
      report will serve to familiarize the pediatrician with currently accepted
      criteria defining the spectrum of autism, strategies used in making a diagnosis,
      and conventional and alternative interventions.

PMID- 11331714
TI  - Scooter injuries in children.
AB  - OBJECTIVE: To describe a series of nonmotorized scooter-related injuries to
      children to increase public awareness and encourage prevention of such injuries.
      DESIGN: A descriptive study of a consecutive series of patients. SETTING: The
      pediatric emergency service of a municipal hospital. PARTICIPANTS: All children
      <18 years old who presented to the Pediatric Emergency Service (PES) with a
      scooter-related injury from July through September 2000. METHODS: Patients were
      identified by review of the PES medical records. Charts were reviewed for patient
      data including age, place of injury, use of protective gear, adult supervision,
      injury sustained, medical management, and disposition. RESULTS: There were 15
      children treated in the PES for scooter-related injuries. The mean age was 7.8
      years, 73% were male. Approximately 90% of injuries occurred as a result of
      falling off a scooter. Irregular pavement caused 3 falls and tandem riding caused
      2 falls. Inability to use the foot brake caused 1 collision, and 1 child was hit
      by a motor vehicle while crossing the street. Injuries occurred in a park (33%),
      on a sidewalk (47%), in a home (13%), and on the street (7%). Adult supervision
      was present in half of the cases. Only 2 children were wearing helmets at the
      time of injury; none wore protective padding. Five children (33%) suffered head
      trauma; 1 lost consciousness, and 2 suffered amnesia. Three children required a
      head computed tomography scan, and 1 required cervical spine radiographs. All
      radiographs were negative. None of these 5 children were wearing helmets. Seven
      children (47%) sustained facial injuries, and 4 of these children required
      laceration repair. Seven children (47%) sustained extremity trauma, including 1
      laceration and 6 fractures (1 supracondylar, 1 distal radius, 2 radius/ulnar, 1
      tibia/fibula, and 1 patella). Four fractures involved the upper extremity. Four
      fractures were managed by closed reduction; 2 required operative repair. One
      child required splinting of an avulsed tooth. Three of the children (20%) were
      admitted. The 5 children with head trauma were observed and released. CONCLUSION:
      The use of nonmotorized scooters by children may result in serious injury,
      particularly in the young child. Although not life-threatening, these injuries
      require significant medical intervention and may result in permanent functional
      and cosmetic deformity. These injuries are potentially preventable with the
      proper use of protective gear and supervision. Public and parental awareness and
      education are essential to prevent additional injuries.

PMID- 11331715
TI  - Career planning for pediatric residents.
AB  - After having made decisions about college, medical school, and specialty
      training, some residents may delay consideration of their future career in
      pediatrics. Others, having decided what path they will pursue, are not clear as
      to what steps need to be taken to ensure that they approach their choice armed
      with the most appropriate and accurate information. Residents seek career choice
      information from various sources. For many, the resources may not be able to
      provide as complete information in all facets of career decision-making. An
      Internet accessible site for career planning for pediatric residents has been
      developed (). The advantages, beyond ease of access by all residents, are many,
      particularly the power of links to other Internet resources. In addition, a
      website provides the ability to rapidly update and add information, which is not
      feasible in printed form. career planning, pediatric residents, jobs, private
      practice, pediatric specialties.

PMID- 11331716
TI  - Serologic evidence for Cryptococcus neoformans infection in early childhood.
AB  - OBJECTIVE: Cryptococcus neoformans is an important cause of central nervous
      system infection in adults with acquired immunodeficiency syndrome (AIDS) but an
      unusual cause of disease in children with AIDS. The basis for this age-related
      difference in incidence is not known but may be caused by differences in exposure
      or immune response. The objective of this study was to determine whether the low
      prevalence of cryptococcal disease among children is related to a lack of
      exposure to C neoformans. METHODS: Sera were obtained from 185 immunocompetent
      individuals ranging in age from 1 week to 21 years who were being evaluated in an
      urban emergency department. Sera were analyzed for antibodies to C neoformans and
      Candida albicans proteins by immunoblotting. Immunoblot patterns were compared
      with those obtained from sera of patients with cryptococcosis (n = 10) and
      workers in a laboratory devoted to the study of C neoformans. The specificity of
      our results was confirmed by several approaches, including antibody absorption
      and blocking studies. Sera were also analyzed for the presence of cryptococcal
      polysaccharide by both enzyme-linked immunosorbent assay and latex agglutination
      assays. RESULTS: Sera from children 1.1 to 2 years old demonstrated minimal
      reactivity to C neoformans proteins. In contrast, the majority of sera from
      children >2 years old recognized many (>/=6) C neoformans proteins. For children
      between 2.1 and 5 years old, 56% of sera (n = 25) reacted with many proteins,
      whereas for children >5 years old (n = 120), 70% of samples reacted with many
      proteins. Reactivity was decreased by absorbing sera with C neoformans extracts
      or by preincubating blots with sera from experimentally infected but not from
      control rats. Reactivity to C neoformans proteins did not correlate with
      reactivity to C albicans proteins, which was common in sera from children between
      the ages of 1.1 and 2 years. Cryptococcal polysaccharide was detected at a titer
      of 1:16 (~10 ng/mL) in the sera of 1 child, a 5.6-year-old boy who presented to
      the emergency department with vomiting. CONCLUSIONS: Our findings provide both
      indirect and direct evidence of C neoformans infection in immunocompetent
      children. Our results indicate that C neoformans infects a majority of children
      living in the Bronx after 2 years old. These results are consistent with several
      observations: the ubiquitous nature of C neoformans in the environment, including
      its association with pigeon excreta; the large number of pigeons in urban areas;
      and the increased likelihood of environmental exposure for children once they
      have learned to walk. The signs and symptoms associated with C neoformans
      infection in immunocompetent children remained to be determined. Primary
      pulmonary cryptococcosis may be asymptomatic or produce symptoms confused with
      viral infections and, therefore, not recognized as a fungal infection. Our
      results suggest that the low incidence of symptomatic cryptococcal disease in
      children with AIDS is not a result of lack of exposure to C neoformans. These
      findings have important implications for C neoformans pathogenesis and the
      development of vaccine strategies.

PMID- 11331718
TI  - Assessing an educational intervention to improve physician violence screening
      skills.
AB  - OBJECTIVES: Health professionals play an integral role in assessing the risk of
      violence in their patients. However, there have been few evaluations of violence
      prevention education programs for health care personnel. The objective of this
      study was to evaluate the effects of a violence-screening education program on
      pediatric residents' and medical students' comfort level and skills in the
      identification and management of violence risks. SETTING: Adolescent clinic of a
      tertiary care pediatric hospital. PARTICIPANTS: Fifty-six second-year residents
      and third-year medical students assigned to a 4-week adolescent clinic rotation.
      DESIGN: Randomized, controlled comparison study conducted over a 1-year period.
      INTERVENTION: On alternate months, medical students and residents in the
      intervention group participated in a 3-hour workshop on violence prevention. The
      workshop included a didactic session with an overview of firearm, media, and
      sexual violence; a discussion of risk factors for adolescent violence; and
      training on the approach to the adolescent interview. Participants also discussed
      violence risks in the community with a panel of teen health educators, engaged in
      one-on-one role play with the youth educators, and received feedback on their
      violence screening skills. The control group received the standard ambulatory
      clinic manual with articles on violence prevention. EVALUATION METHODS: All
      participants completed prerotation and postrotation questionnaires assessing
      their self-reported screening practices, as well as perceived importance and
      confidence in violence screening. Participants also interviewed and examined an
      adolescent standardized patient (SP) in the clinic. SPs completed evaluations on
      the content of the residents' and students' screening, their interpersonal
      skills, and their skill in the identification and management of the violence
      related problem. RESULTS: Over 12 months, 30 control and 26 intervention
      participants were recruited. There were no differences in prerotation
      questionnaire scores for intervention and control groups in screening practices,
      perceived importance and confidence in violence screening. Postrotation
      intervention participants reported more screening compared with controls on
      violence in school/neighborhood and fighting history. There was also greater
      perceived importance in asking about access/use of weapons and violence in
      school/neighborhood. Intervention participants also had improved performance
      compared with controls on SP evaluations of screening for violence,
      identification and management of the violence-related scenario, and interpersonal
      skills. CONCLUSION: A violence prevention education program with teen health
      educators improved participants' self-reported violence questioning, as well as
      increased perceived comfort and importance in violence screening. Participants in
      the program also improved their identification and management of a standardized
      violence-related scenario presented in an adolescent clinic setting. adolescent
      violence, physician education, violence risk screening.

PMID- 11331717
TI  - Home and videotape intervention delays early complementary feeding among
      adolescent mothers.
AB  - BACKGROUND: The American Academy of Pediatrics, the Special Supplemental
      Nutrition Program for Women, Infants, and Children (WIC), and the World Health
      Organization recommend that infants receive only breast milk or formula for the
      first 4 to 6 months of life, followed by the introduction of complementary foods.
      Despite these recommendations, many infants, particularly those with adolescent
      mothers, receive solid foods (often cereal mixed with formula in a bottle) and
      liquids other than formula or breast milk in the first few weeks of life.
      Decisions on early feeding are often guided by grandmothers and influenced by
      beliefs that infants need complementary food to counteract signals of hunger,
      reduce crying, and sleep through the night. OBJECTIVE: This investigation
      evaluated the efficacy of an intervention to delay the early introduction of
      complementary feeding among first-time, black, adolescent mothers living in
      multigenerational households. The intervention focused on reducing the cultural
      barriers to the acceptance of the recommendations of the American Academy of
      Pediatrics, WIC, and World Health Organization on complementary feeding by
      highlighting 3 topics: 1) recognition of infants' cues; 2) nonfood strategies for
      managing infant behavior; and 3) mother-grandmother negotiation strategies. The
      intervention was delivered through a mentorship model in which a videotape made
      by an advisory group of black adolescent mothers was incorporated into a home
      visiting program and evaluated through a randomized, controlled trial. METHODS:
      One hundred eighty-one first-time, low-income, black mothers <18 years old,
      living in multigenerational households were recruited from 3 urban hospitals.
      Infants were born at term, with birth weight appropriate for gestational age and
      no congenital problems. Shortly after delivery, mothers and grandmothers
      completed a baseline assessment and mothers were randomized into an intervention
      or control group. Intervention group mothers received home visitation every other
      week for 1 year. At 3 months, a subset of 121 adolescent mothers reported on
      their infant's intake through a food frequency questionnaire. Mothers who fed
      their infant only breast milk, formula, or water were classified as optimal
      feeders. Mothers who provided complementary foods other than breast milk,
      formula, or water were classified as less optimal feeders. RESULTS: Sixty-one
      percent of the infants received complementary foods before 3 months old.
      Multivariate hierarchical logistic regression was used to evaluate the
      determinants of being in the optimal versus less optimal feeders group. After
      controlling for infant age and family income, mothers of infants in the optimal
      feeders group were more likely to report accurate messages from WIC regarding the
      timing of complementary food and nearly 4 times more likely to be in the
      intervention group. The most common complementary food was cereal mixed with
      formula in the bottle. CONCLUSIONS: The success of this relatively brief
      intervention demonstrates the importance of using ecological theory and
      ethnographic research to design interventions that enable participants to alter
      their behavior in the face of contradictory cultural norms. The intervention
      focused on interpreting infants' cues, nonfood methods of managing infant
      behavior, and mother-grandmother negotiations. It was delivered through methods
      that were familiar and acceptable to adolescent mothers-a mentorship model
      incorporating home visits and videotape. The skill-oriented aspects of the
      intervention delivered in a culturally sensitive context may have enabled the
      young mothers to follow the guidelines that they received from WIC and from their
      pediatricians. Strategies, such as those used in this intervention, may be
      effective in promoting other caregiving recommendations, thereby enabling
      providers to meet the increasing demands from parents for advice regarding
      children's early growth and development.

PMID- 11331719
TI  - A syndrome of transient encephalopathy associated with adenovirus infection.
AB  - BACKGROUND AND OBJECTIVE: Adenovirus is a common pathogen in the pediatric
      population. Respiratory, gastrointestinal, or renal systems are often involved in
      adenovirus infections. Several neurologic syndromes have been attributed to
      adenovirus, such as adenovirus aseptic meningitis, myelitis, subacute focal
      encephalitis, and Reye-like syndrome. The purpose of this study was to describe
      the clinical features and encephalography findings in 7 infants treated in our
      center for a syndrome of transient encephalopathy associated with adenovirus
      infection. STUDY PARTICIPANTS: Three females and 4 males ages 7 to 34 months seen
      in our department between July 1983 and February 1984 and September 1998 and May
      1999 presented with fever of at least 7 days' duration and a gradual decline in
      the state of alertness. Score on the Glasgow Coma Scale ranged from 9 to 12.
      Findings on lumbar puncture were normal. In all 7 patients, the encephalogram
      showed moderate to severe background slowing compatible with encephalopathy. All
      patients were catarrheal and had mild hepatomegaly with slight elevation of liver
      enzymes. Some had bronchopneumonia, diarrhea, and conjunctivitis either isolated
      or in combination. METHODS AND RESULTS: Adenovirus was isolated by
      immunfluorescence technique in all patients-from the sputum in 3 patients,
      nasopharynx in 5, conjunctiva in 4, and rectal swab in 5. In 5 patients,
      serotyping was performed by an antibody neutralization method. Adenovirus type 3
      was ascertained from a nasal swab in 1 patient, sputum specimens in 3, throat
      swab in 3, and rectal cultures in 5. The clinical course was characterized by a
      progressive recovery of alertness. After several days, there was a complete
      reversal of neurologic findings. CONCLUSION: We suggest that this syndrome of
      transient encephalopathy is a distinct entity and should be considered as another
      of the several neurologic syndromes known to be associated with adenovirus
      infection.

PMID- 11331720
TI  - Adolescents with cystic fibrosis: family reports of adolescent health-related
      quality of life and forced expiratory volume in one second.
AB  - PURPOSE: To assess the relationship between adolescent and parent reports of
      adolescent health-related quality of life (HRQL) and between adolescent pulmonary
      function (forced expiratory volume in 1 second as percent of predicted) and
      reporter perceptions of adolescent health. METHODS: Twenty-four adolescents with
      cystic fibrosis (CF), their mothers, and their fathers completed the Child Health
      Questionnaire during routine CF clinic visits at 2 urban hospitals. Patients were
      between the ages of 11 and 18 years (mean age: 14.2 years) and were predominantly
      male (75%). The best measure of forced expiratory volume in 1 second as percent
      of predicted for the year of the study was also collected for each adolescent.
      RESULTS: Adolescent pulmonary function was related to the perceived adolescent
      physical health scales. It was not, however, associated to perceptions of
      adolescent emotional, social, or behavioral HRQL by any of the 3 family
      reporters. Associations were found between adolescent pulmonary function and self
      reports of general health (0.73), role/social limitations-physical (0.47), and
      bodily pain (0.42). Adolescent pulmonary function was related to mother reports
      of adolescent general health (0.73), role/social limitations-physical (0.73),
      bodily pain (0.55), and physical functioning (0.70). Father perceptions of
      adolescent health were associated to adolescent pulmonary function on general
      health (0.54), role/social limitations-physical (0.60), and physical functioning
      (0.64). Associations between adolescent and parent perceptions of adolescent HRQL
      were also health scale-specific. Mother and child reports of adolescent HRQL were
      related on adolescent behavior problems (0.71) and role/social limitations
      attributable to behavior (0.48), role/social limitations attributable to physical
      (0.62), bodily pain (0.69), physical functioning (0.69), family activities
      (0.45), and general health (0.66). Associations were found between father and
      adolescent reports on perceived adolescent behavior problems (0.66); self-esteem
      (0.65); and role/social limitations attributable to physical (0.49), general
      health (0.61), and perceived mental health (0.48). CONCLUSIONS: Results
      demonstrate the need to include multiple informants and comprehensive,
      multidimensional measures of HRQL, in addition to pulmonary function, when
      assessing health in adolescents with CF.

PMID- 11331721
TI  - Repeated doses of porcine secretin in the treatment of autism: a randomized,
      placebo-controlled trial.
AB  - BACKGROUND AND OBJECTIVES: Anecdotal reports on the efficacy of secretin in
      autism raised great hopes for the treatment of children with this disorder.
      Initial single-dose, randomized, controlled trials failed to demonstrate any
      therapeutic effects of secretin. The present study is the first to test the
      outcome of repeated doses and to examine whether there is a subgroup of children
      who are more likely to achieve positive effects. METHOD: Sixty-four children with
      autism (ages 2-7 years; 55 boys and 9 girls) with a range of intelligence
      quotient and verbal ability were randomly assigned, in a double-blind manner, to
      secretin or placebo groups. Children received 2 doses of placebo or porcine
      secretin, 6 weeks apart. Assessments were performed at baseline and 3 weeks after
      each injection using several outcome measures. RESULTS: There were no group
      differences on formal measures of language, cognition, or autistic
      symptomatology. Subgroupings based on cognitive level, the presence or absence of
      diarrhea, or a history of regression failed to show any significant therapeutic
      effects of secretin. CONCLUSION: No evidence is provided for the efficacy of
      repeated doses of porcine secretin in the treatment of children with autism. The
      possible relationship between relief of biological symptoms and enhanced skill
      performance is discussed.

PMID- 11331722
TI  - Dating violence and the sexual health of black adolescent females.
AB  - OBJECTIVE: This study examines the association between having a history of dating
      violence and the sexual health of adolescent females. METHODS: Black adolescent
      females (n = 522) completed a survey that assessed dating violence, defined as
      ever having a physically abusive boyfriend, and an interview that assessed sexual
      behaviors. RESULTS: Dating violence was reported by 18.4% of adolescents (n =
      96). Adolescents with a history of dating violence were, in the past 6 months,
      2.8 times more likely to have a sexually transmitted disease, 2.8 times more
      likely to have nonmonogamous male partners, and half as likely to use condoms
      consistently. Furthermore, adolescents with a history of dating violence were
      significantly more likely to fear the perceived consequences of negotiating
      condom use (odds ratio [OR] = 2.8); fear talking with their partner about
      pregnancy prevention (OR = 2.6); have a higher perceived risk of acquiring a
      sexually transmitted disease (OR = 2.1); perceive less control over their
      sexuality (OR = 2.4); have peer norms nonsupportive of using condoms (OR = 3.1);
      and have norms nonsupportive of having a healthy relationship (OR = 2.1).
      CONCLUSIONS: Adolescents who have experienced dating violence are more likely to
      exhibit a spectrum of unhealthy sexual behaviors, attitudes, beliefs, and norms.

PMID- 11331723
TI  - Risk assessment for gonococcal and chlamydial infections in young children
      undergoing evaluation for sexual abuse.
AB  - OBJECTIVE: Testing for gonorrhea (GC) and chlamydial (Ct) infection in children
      who are being evaluated for sexual abuse is invasive and costly. We developed
      selective criteria to limit unnecessary testing for these infections. METHODS:
      Over a 10-year period (May 1988 to May 1998), clinical information was collected
      in a prospectively designed database for all children ages 0 to 12 years by the
      WakeMed Child Sexual Abuse Team in Raleigh, North Carolina. The study population
      comprised 3040 (2414 girls and 626 boys) of the 3064 children evaluated for
      sexual abuse. Children were interviewed, examined, and tested by culture for GC
      and Ct orally, rectally, and genitally. Information from referral sources,
      accompanying guardians, and previous recent physical examinations was recorded.
      Bivariate analyses and logistic regression were used to develop 2 sets of
      screening criteria to predict children at greatest risk of infection with: 1) GC
      and/or Ct (GC/Ct) and 2) GC alone. RESULTS: Fifty-eight children were identified
      with GC/Ct infections (37 with GC, 25 with Ct; 4 children were coinfected). The
      proposed algorithm for GC/Ct infections would have identified all children with
      these infections, while avoiding testing 56% of children without infection. Using
      genital cultures only, the proposed risk score for GC/Ct infections would have
      identified 100% of GC/Ct cases with 85% fewer cultures compared with testing all
      children with oral, rectal, and genital cultures. CONCLUSION: The use of a risk
      assessment algorithm for GC and Ct infections may reduce the cost and trauma of
      testing young children who are being evaluated for sexual abuse. sexual abuse,
      gonorrhea, Neisseria gonorrhoeae, chlamydia, Chlamydia trachomatis, sexually
      transmitted diseases, children.

PMID- 11331724
TI  - The search for congenital malformations in newborns with fetal cocaine exposure.
AB  - CONTEXT: The association between prenatal cocaine exposure and congenital
      anomalies is not definitive. OBJECTIVE: To determine whether prenatal cocaine
      exposure results in an increased number or identifiable pattern of abnormalities.
      DESIGN: A prospective, longitudinal cohort enrolled between 1991 and 1993.
      SETTING: Rural public health population delivering at a regional tertiary medical
      center. PATIENTS: Two hundred seventy-two offspring of 154 prenatally identified
      crack/cocaine users and 154 nonusing controls were matched on race, parity,
      location of prenatal care (that related to level of pregnancy risk), and
      socioeconomic status. Drug use was determined through repeated in-depth histories
      and urine screens. Infants not examined within 7 days of birth were excluded.
      OUTCOME MEASURES: Assessments were made by experienced examiners masked to
      maternal drug history. Included were 16 anthropometric measurements and a
      checklist of 180 physical features defined and agreed upon in advance. RESULTS:
      There were no differences on major risk variables between the included and
      excluded infants. There were significantly more premature infants in the cocaine
      exposed group. Cocaine-exposed infants were significantly smaller in birth
      weight, length, and head circumference but did not differ on remaining
      anthropometric measurements. There was no difference in type or number of
      abnormalities identified between the exposed and nonexposed groups. There was no
      relationship between amount or timing of exposure and any of the outcomes.
      CONCLUSIONS: This prospective, large-scale, blinded, systematic evaluation for
      congenital anomalies in prenatally cocaine-exposed children did not identify an
      increased number or consistent pattern of abnormalities.

PMID- 11331725
TI  - Worldwide timing of growth faltering: implications for nutritional interventions.
AB  - OBJECTIVE: It is widely assumed that growth faltering starts at around 3 months
      of age, but there has been no systematic assessment of its timing using
      representative national datasets from a variety of countries. METHODOLOGY: The
      World Health Organization Global Database on Child Growth and Malnutrition
      includes the results of 39 nationally representative datasets from recent surveys
      in developing countries. Based on these data, mean z scores of weight for age,
      length/height for age, and weight for length/height were compared with the
      National Center for Health Statistics and Cambridge growth references, for
      children younger than 60 months. RESULTS: Mean weights start to falter at about 3
      months of age and decline rapidly until about 12 months, with a markedly slower
      decline until about 18 to 19 months and a catch-up pattern after that. Growth
      faltering in weight for length/height is restricted to the first 15 months of
      life, followed by rapid improvement. For length/height for age, the global mean
      is surprisingly close to National Center for Health Statistics and Cambridge
      references at birth, but faltering starts immediately afterward, lasting well
      into the third year. CONCLUSIONS: These findings highlight the need for prenatal
      and early life interventions to prevent growth failure.

PMID- 11331726
TI  - Influence of day care attendance on the use of systemic antibiotics in 0- to 2
      year-old children.
AB  - OBJECTIVE: To examine the association between time spent in different public day
      care settings and prescription of systemic antibiotics. Design. Population-based
      cohort study of 5035 Danish children born in 1997 followed from birth to June 30,
      1999. METHODS: The study was performed by the linkage of records drawn from
      administrative registries. Exposure was the total time spent in a day care home
      or day care center. Outcome was the first prescription of a systemic antibiotic.
      Possible perinatal and sociodemographic confounding factors were considered by
      statistical analysis. RESULTS: During the first year of life, 39.8% of the girls
      and 51.1% of the boys received at least 1 antibiotic prescription drug.
      Enrollment in a day care setting doubled a child's risk of receiving a
      prescription drug (adjusted relative risk in day care home 1.9, 95% confidence
      interval: 1.7-2.0; adjusted relative risk in day care center 2.0, 95% confidence
      interval: 1.7-2.3). Only age confounded the analyses. Age >1 year at the starting
      time in day care reduced the risk of receiving antibiotic prescriptions during
      the first 3 months after enrollment. CONCLUSIONS: Enrollment in public day care
      facilities raised the risk of receiving an antibiotic prescription drug to the
      same extent in day care homes as well as in day care centers, so we cannot
      recommend one facility over the other based on the present study. Children <1
      year old at enrollment were most at risk, suggesting that extension of parental
      leave may reduce the use of antibiotics.

PMID- 11331728
TI  - Multisite survey of pediatric residents' continuity experiences: their
      perceptions of the clinical and educational opportunities.
AB  - OBJECTIVES: To survey a large group of residents from different institutions to
      delineate whether there are significant perceptive differences pertaining to the
      clinical and educational strengths and weaknesses of their continuity experiences
      by the 3 types of continuity sites. BACKGROUND: The residency review committee
      requires a 3-year continuity experience for pediatric residents. Residents
      receive this experience at a variety of practice sites: hospital-based sites
      (HBS), community health centers (CHC), and private practices (PP)/health
      maintenance organizations (HMOs). DESIGN/METHODS: Continuity clinic directors who
      attended the Ambulatory Pediatric Association Continuity Clinic Special Interest
      Group at the 1999 annual Pediatric Academic Societies Meeting were invited to
      participate in this cross-sectional study. Thirty-six agreed and distributed a 60
      item questionnaire to their residents at the end of the academic year. The
      questionnaire addressed quality and quantity of the educational and patient care
      experiences, overall satisfaction, and future career plans. RESULTS: Of the 1167
      categorical residents (71%) who returned the questionnaire, 28% were postgraduate
      level (PL)-1s, 34% were PL-2s, and 37% were PL-3s. Ninety-four percent of the 36
      programs had residents in HBS (n = 807 residents), 58% in CHC (n = 106), and 69%
      in PP/HMO (n = 254). Compared with other groups, residents in HBS were more
      likely to report having seen patients more than once, being involved during
      patients' hospitalizations, taking phone calls from patients, and perceiving that
      the parents identified them as the primary care provider. HBS and CHC residents
      felt more autonomous and were more likely to believe that they were advocates for
      their patients, compared with PP/HMO residents. The number of patients seen per
      session was greater in PP/HMO, whereas residents in PP/HMO were more likely to
      perceive that they had received the right amount of exposure to practice
      management and billing issues and the appropriate amount of nursing and office
      support. Although numbers of newborn visits were reported as adequate across
      sites, residents in HBS and CHC believed that they did not see enough
      adolescents. The majority of residents at all sites agreed that their preceptor
      was a good role model, was available for questions, and delivered the appropriate
      amount of teaching and feedback. Approximately two thirds of residents from all
      sites were satisfied with their experience and believed that it was preparing
      them for their future career. CONCLUSIONS: All 3 types of continuity sites have
      both strengths and weaknesses. No single type of continuity site met all
      expectations for clinical care or training. Most residents at all 3 types of
      sites reported overall satisfaction and believed that their continuity experience
      helped to prepare them for future career goals. The residency review committee,
      in collaboration with pediatric continuity educators, needs to prioritize what
      constitutes the essential experiences in resident continuity practices and to
      reemphasize that the ongoing relationship is an important component of the
      continuity experience.

PMID- 11331727
TI  - The effect of protease inhibitor therapy on growth and body composition in human
      immunodeficiency virus type 1-infected children.
AB  - OBJECTIVE: To determine the effect of protease inhibitors (PIs) on growth and
      body composition in children with human immunodeficiency virus type 1 (HIV-1)
      infection. BACKGROUND: HIV-1-infected children have chronic problems with both
      linear growth and weight gain. Viral load may directly influence growth and
      nutritional status of HIV-1-infected children with reduction of viral load
      improving the nutritional condition. DESIGN/METHODS: Data from 67 patients who
      initiated PI therapy between 1996 and 1999 and who were enrolled in a
      prospective, longitudinal study of growth and nutrition in HIV-1-infected
      children were analyzed. Outcomes included pre-PI versus post-PI measures of
      height, weight, weight-for-height, triceps skinfold thickness, and arm muscle
      circumference. Predictor covariates included age, race, gender, Tanner stage, CD4
      z score, Centers for Disease Control and Prevention stage, route of infection,
      plasma HIV-1 RNA, other antiretroviral therapy, recommended daily allowances for
      calories, treatment with megestrol acetate, and PI therapy. RESULTS: Sixty-seven
      children were followed for a median of 2.4 years with a total of 362 visits
      (median: 5 visits; range: 1-12). During follow-up, they received PIs for a median
      of 5 months. Fifty-one percent were girls, 54% black, 15% Hispanic, and 25%
      white. The mean age at first visit was 6.8 years. In a univariate analysis,
      weight z score (-0.67 to -0.35) and weight/height z score (0.25-0.76) improved on
      PI therapy. Using repeated-measures regression analysis, controlling for the
      above named covariates, PI treatment showed a significant effect on weight z
      score (increase in z score by 0.46), weight/height z score (increase in z score
      by 0.49), and arm muscle circumference (increase in percentile by 11.5). A
      borderline effect was found for height z score (increase in z score by 0.17) and
      no effect was found for triceps skinfold thickness. In a separate analysis, PI
      therapy increased CD4 counts twofold and reduced plasma HIV-1 RNA copies by 79%.
      CONCLUSION: In addition to a significant reduction in viral load, PI therapy in
      children has a positive effect on several growth parameters, including weight,
      weight/height, and muscle mass.

PMID- 11331729
TI  - Reduced spinal bone mineral density in adolescents of an Ultra-Orthodox Jewish
      community in Brooklyn.
AB  - OBJECTIVES: Bone mass increases throughout childhood, with maximal bone mass
      accrual rate occurring in early to mid-puberty and slowing in late puberty.
      Prevention of osteoporosis and its morbidities depends primarily on the
      establishment of adequate peak bone mass. Physical activity, calcium intake, and
      vitamin D stores (from sunlight conversion of precursors of vitamin D and to a
      lesser degree from dietary intake) are vital determinants of bone mineral density
      (BMD). BMD is further controlled by genetic and environmental factors that are
      poorly understood. Observance of ultra-Orthodox Jewish customs may have a
      negative effect on the factors that promote bone health, and there have been
      anecdotal reports of higher fracture rates in this population. The ultra-Orthodox
      Jewish lifestyle encourages scholarly activity in preference to physical
      activity. Additionally, modest dress codes and inner-city dwelling reduce
      sunlight exposure. Orthodox Jews do not consume milk products for 6 hours after
      meat ingestion, leading to potentially fewer opportunities to consume calcium.
      Foods from the milk group are some of the best sources of dietary calcium. Our
      aims are to examine BMD in a group of healthy ultra-Orthodox Jewish adolescents
      in an urban community and to attempt to correlate it to physical activity and
      dietary factors. DESIGN AND METHODS: We recruited 50 healthy, ultra-Orthodox
      Jews, ages 15 to 19 years (30 males and 20 females). None were taking
      corticosteroids or had evidence of malabsorption. All girls were postmenarchal
      and nulliparous. Pubic hair Tanner stage for boys and breast Tanner stage for
      girls were determined. Weight and height standard deviation scores were
      calculated. Calcium, phosphorus, protein, vitamin D, and calorie intake were
      assessed using a comprehensive food questionnaire referring to what has been
      eaten over the last year. Hours per week of weight-bearing exercise and walking
      were determined. Serum levels of calcium, intact parathyroid hormone (PTH), 25
      hydroxyvitamin D (25[OH]D) and 1,25 dihydroxyvitamin D (1,25[OH](2)D) were
      measured. Lumbar spine (L) BMD was assessed by dual energy radiograph
      absorptiometry. The pediatric software supplied by Lunar Radiation Corporation,
      which contains gender- and age-specific norms, provided a z score for the lumbar
      BMD for each participant. L2 to L4 bone mineral apparent density (BMAD) was
      calculated from L2 to L4 BMD. RESULTS: BMD of L2 to L4 was significantly
      decreased compared with age/sex-matched normative data: mean z score was -1.25 +/
      1.25 (n = 50). The mean L2 to L4 BMD z score +/- standard deviation was -1.71 +/
      1.18 for boys and -0.58 +/- 1.04 for girls. Eight boys (27%) had L2 to L4 BMD z
      scores <-2.5, which defines osteoporosis in adulthood. Twenty-seven adolescents
      (54%), 16 boys and 11 girls, had Tanner stage V. Two participants (4%) had
      delayed development of Tanner stage V. Mean consumption of calcium by
      participants under 19 years old was 908 +/- 506 mg/day (n = 46), which is lower
      than the adequate intake of 1300 mg/day for this age. The consumption of
      phosphorus was 1329 +/- 606 mg/day, and the consumption of vitamin D was 286 +/-
      173 IU/day (n = 50). The mean serum 25(OH)D level was 18.4 +/- 7.6 ng/mL, and the
      mean serum 1,25(OH)(2)D level was 71.1 +/- 15.7 pg/mL (n = 50). Boys had
      significantly higher serum levels of 1,25(OH)(2)D than did girls (74.9 +/- 16.46
      pg/mL vs 65.25 +/- 12.8 pg/mL, respectively). The serum levels of PTH, calcium,
      and protein were (mean +/- standard deviation): 33 +/- 16 pg/mL, 9.5 +/- 0.69
      mg/dL, and 7.8 +/- 0.6 g/dL, respectively (n = 50). L2 to L4 BMD z score had
      positive correlation with walking hours (r = 0.4). L2 to L4 BMD z score had
      negative correlation with serum level of 1,25(OH)(2)D )r = -0.33; n = 50). We
      could not find significant correlation between L2 to L4 BMD z scores for the
      entire cohort and any of calcium, vitamin D, phosphorus, or protein intake.
      However, the L2 to L4 BMD z scores of boys had positive correlation with calcium,
      phosphorus, and protein intake (r = 42, r = 44, and r = 43, respectively). After
      adjustment for Tanner stage, boys who had Tanner stage V (n = 16) had stronger
      positive correlation between L2 to L4 BMD z scores and calcium and protein intake
      (r = 0.55 and r = 0.57, respectively), as was the correlation between L2 to L4
      BMD z score and weight-bearing activity and walking hours (r = 0.77 and r = 0.72,
      respectively; n = 16). By multiple regression analysis with stepwise selection,
      sex, walking hours, weight-standard deviation scores, and serum PTH predicted 54%
      of the variability in L2 to L4 BMD z score. Sex, walking hours, and age predicted
      65% of the variability in L2 to L4 BMAD. CONCLUSIONS: Lumbar BMD is significantly
      decreased in ultra-Orthodox Jewish adolescents living in an urban community. Boys
      had profoundly lower spinal BMD than did girls. Previous studies have introduced
      estrogen as a critical factor in bone mineralization. (ABSTRACT TRUNCATED)

PMID- 11331730
TI  - Sensitization to silk and childhood asthma in rural China.
AB  - OBJECTIVE: Sensitization to perennial aeroallergens is associated with asthma in
      industrialized countries with a Western lifestyle. Because silk products are
      commonly used in Chinese society, we were interested in examining the relation
      between sensitization to silk and asthma. DESIGN: Cross-sectional study of 871
      children in 503 families living in Anqing, a predominantly rural province of
      China. RESULTS: After adjustment for age, gender, familial correlations, and
      sensitization to other aeroallergens, skin test reactivity to silk was an
      independent predictor of asthma (odds ratio = 2.6; 95% confidence interval = 1.2
      5.7). This association became stronger after inclusion of the eosinophil count
      and history of parasitic diseases of the participants in the multivariate model
      (odds ratio = 3.6; 95% confidence interval = 1.4-8.9). CONCLUSION: Because
      sericulture is an important activity in China and other countries throughout the
      world, sensitization to silk may influence the pathogenesis and severity of
      asthma in people living in these nations.

PMID- 11331731
TI  - A comparison of elevated blood lead levels among children living in foster care,
      their siblings, and the general population.
AB  - OBJECTIVES: To assess the prevalence of elevated blood lead levels (EBLLs) among
      children before and after foster care placement, and to compare the prevalence of
      EBLLs among children in foster care with that of their siblings and the general
      population. METHODS: We conducted a retrospective cohort study using
      administrative databases from the Philadelphia Department of Human Services and
      the Birth Certificate Registry and the Childhood Lead Poisoning Prevention
      Program at the Philadelphia Department of Public Health. Logistic regression
      analyses were performed to control for confounding variables, including age,
      race, gender, and the year, seasonal timing, and source (capillary vs venous) of
      test. RESULTS: From June 1992 to May 1997, there were 1824 children in foster
      care with available blood lead results in the Childhood Lead Poisoning Prevention
      Program database. Of these, 519 (28%) had initial lead screening before foster
      care placement and 654 (36%) after placement. There were 821 siblings and 73 608
      children in the general population with available blood lead results. Before
      entering foster care, children were nearly twice as likely to have EBLLs as their
      siblings (adjusted odds ratio [OR] = 1.7; 95% confidence interval [CI] = 1.4,
      2.0), those in placement (adjusted OR = 1.9; 95% CI = 1.6, 2.2), and the general
      population (adjusted OR = 1.7; 95% CI = 1.5, 2.0). At the highest point
      prevalence, 50% of children before placement had lead levels >/=20 microg/dL, and
      nearly 90% had levels >/=10 microg/dL. For all age categories, siblings of
      children in foster care placement had a higher prevalence of EBLLs than did the
      general population. After placement, children in foster care were nearly half as
      likely as the other groups to have EBLLs. CONCLUSIONS: Our findings suggest that
      children are at high risk for lead poisoning before entering foster care and that
      placement in foster care may have a beneficial effect on lead exposure. Children
      before foster care placement are nearly twice as likely to have EBLLs compared
      with children in foster care placement, the general population, and their
      siblings. Furthermore, siblings of children in foster care are at high risk for
      lead poisoning. Children receiving social services in their own homes and
      children suffering from abuse and neglect should be actively screened for lead
      poisoning. Greater efforts at preventing lead poisoning among these children must
      be made.

PMID- 11331732
TI  - Lymphomatoid granulomatosis after childhood acute lymphoblastic leukemia: report
      of effective therapy.
AB  - Lymphomatoid granulomatosis, a rare condition in children, affects the lungs
      primarily but may have significant extrapulmonary manifestations, especially in
      the central nervous system. We report a case of lymphomatoid granulomatosis with
      onset after the completion of chemotherapy for childhood acute lymphoblastic
      leukemia. Two months after treatment ended, the 7-year-old girl developed
      splenomegaly, cervical adenopathy, and bilateral interstitial pulmonary
      infiltrates. She improved on cefotaxime but experienced a seizure 1 month later.
      A computed tomography scan of the head was normal, but her pulmonary infiltrates
      had become nodular. A computed tomography-guided biopsy of 1 of the nodules
      revealed cellular interstitial pneumonitis. One month later, she had persistent
      pulmonary infiltrates, marked splenomegaly, and new seizures. Magnetic resonance
      imaging of the head revealed cerebral nodules. Itraconazole was begun, and the
      pulmonary infiltrates resolved. Five months after her initial symptoms, she
      developed tonic pupil and a decreased level of consciousness. Dexamethasone was
      initiated. Needle biopsies of the brain were carried out, yielding the diagnosis
      of severe chronic inflammatory changes focally consistent with granuloma. The
      child redeveloped splenomegaly and fever, and then suffered an acute
      decompensation with hypoxemia, tachypnea, splenomegaly, and cardiac gallop. Open
      lung biopsy revealed lymphomatoid granulomatosis. Lymphoma-directed therapy was
      initiated, and the patient had complete resolution of pulmonary and cerebral
      nodules 5 months later. No intrathecal chemotherapy was administered, and
      radiation therapy was not necessary. Neuropsychological testing obtained after
      completion of therapy revealed an improvement in attention, coordination, and
      fine motor speed over time. She is now in good health and attending school.

PMID- 11331733
TI  - Surveillance for poliovirus vaccine adverse events, 1991 to 1998: impact of a
      sequential vaccination schedule of inactivated poliovirus vaccine followed by
      oral poliovirus vaccine.
AB  - BACKGROUND: The elimination of wild-virus-associated poliomyelitis in the Western
      Hemisphere in 1991 and rapid progress in global polio eradication efforts changed
      the risk-benefit ratio associated with the exclusive use of oral poliovirus
      vaccine (OPV) for routine immunization. These changes, plus the November 1987
      development of an enhanced-potency inactivated poliovirus vaccine (IPV), which
      poses no risk of vaccine-associated paralytic poliomyelitis (VAPP), resulted in a
      change in polio immunization policy in the United States. In September 1996, the
      Centers for Disease Control and Prevention recommended that IPV replace OPV for
      the first 2 doses in a sequential poliovirus vaccine schedule. The Vaccine
      Adverse Event Reporting System (VAERS), a passive surveillance system for adverse
      events after receipt of any US-licensed vaccine, is used to monitor postlicensure
      vaccine safety. Postlicensure surveillance of vaccines is important to identify
      new, rare, or delayed-onset adverse reactions not detected in prelicensure
      clinical trials or when new vaccine schedules are adopted. Through continual
      monitoring of adverse events and identification of potential vaccine risks, VAERS
      can serve as an important resource to ensure continued public acceptance of
      vaccines. We compared VAERS reports after the receipt of IPV to reports after OPV
      in infants from 1991 through 1998. Comparisons included reports listing IPV and
      OPV coadministered with other vaccines. METHODS: Annual reporting rates per 100
      000 doses distributed within 3 severity categories (fatal, nonfatal serious, less
      serious) were examined. Distributions of severity categories by vaccine type,
      age, and time period (pre- and postrecommendation) were constructed. Safety
      profiles (distribution of 21 symptom groupings) for IPV and OPV reports were
      compared. Analysis was restricted to reports for infants 1 to 3 months old and 4
      to 6 months old, corresponding generally to first- and second-dose recipients.
      Any notable increase in a severity or safety category for IPV compared with OPV
      was followed up by examining the frequency of specific symptoms, reporting
      source, and date of vaccination. An important limitation of VAERS is that reports
      do not necessarily represent adverse events caused by vaccines. In many cases,
      the events are temporal associations only. RESULTS: The annual rates of VAERS
      reports per 100 000 vaccine doses distributed by severity category, 1991 to 1998,
      were in general similar for reports after IPV compared with those after OPV. The
      reporting rates for poliovirus vaccine did not increase materially with the shift
      to IPV usage. The relative frequencies of symptoms in the fatal and nonfatal
      serious categories for 1998 vaccine administrations were similar to 1997 reports.
      Severity profiles for IPV and OPV reports in infants 1 to 3 months old and 4 to 6
      months old, corresponding to first- and second-dose recipients, were remarkably
      similar. The frequency of symptoms listed on IPV reports categorized as fatal or
      serious was examined by age, vaccine combinations, and time period, and the
      distribution of symptoms was similar for ages 1 to 3 months and 4 to 6 months. In
      the postrecommendation period, the 10 most frequent symptoms reported with IPV
      were also reported with OPV in either similar or lower relative frequency. During
      the postrecommendation period, safety profiles for infants 4 to 6 months old
      showed a 2.5% higher proportion in the allergic reaction category for IPV than
      for OPV, but none of the allergic reaction reports indicated anaphylaxis. In
      general, the distribution of symptom groupings was not markedly different for IPV
      compared with OPV. No cases of VAPP were reported after the administration of
      IPV, whereas 5 VAPP cases were reported after the administration of OPV.
      CONCLUSIONS: Although VAERS is subject to the limitations of most passive
      surveillance systems, the large number of reports and national coverage provide a
      unique database for monitoring vaccine safety. There was a marked increase of IPV
      reports in VAERS after 1996, consistent with implementation of the Advisory
      Committee on Immunization Practices recommendation for the sequential IPV/OPV
      poliovirus vaccination schedule. Given the increased use of IPV, a review of
      potential adverse events in VAERS compared IPV with OPV reports both before and
      after the introduction of the sequential vaccination schedule. Vaccine safety
      surveillance indicated no adverse events patterns of potential concern following
      the use of IPV in infants after the introduction of the sequential vaccination
      schedule. Ongoing surveillance is documenting a decrease in VAPP. These findings
      provide useful information to support the Advisory Committee on Immunization
      Practices recommendation, made in 1999, to shift to an all-IPV schedule.

PMID- 11331734
TI  - Measles-mumps-rubella vaccine and autistic spectrum disorder: report from the New
      Challenges in Childhood Immunizations Conference convened in Oak Brook, Illinois,
      June 12-13, 2000.
AB  - BACKGROUND: Parents and physicians are understandably concerned about the causes
      and treatment of autism, a devastating disease that affects the entire family.
      Although much has been learned about autism, there are many gaps in our knowledge
      about what causes the disorder and how it can be prevented. Autistic symptoms
      occur along a spectrum, often referred to as autistic spectrum disorder (ASD).
      Concern has been raised about a possible association between measles-mumps
      rubella (MMR) vaccine and inflammatory bowel disease (IBD) and ASD, especially
      autism with regression. Also, increased requests for educational services related
      to ASD have raised concerns about possible increases in the incidence of ASD.
      METHODS: On June 12-13, 2000, the American Academy of Pediatrics (AAP) convened a
      conference titled "New Challenges in Childhood Immunizations" in Oak Brook,
      Illinois. At this conference, parents, practitioners, and scientists presented
      information and research on MMR vaccine and ASD. Attendees included
      representatives from select AAP committees and sections as well as federal and
      other organizations that address related issues. The multidisciplinary panel of
      experts reviewed data on what is known about the pathogenesis, epidemiology, and
      genetics of ASD and the available data on hypothesized associations with IBD,
      measles, and MMR vaccine. Supplemental information was requested from authors who
      have proposed the hypotheses and other experts in relevant areas. RESULTS: Autism
      is a complex disorder of uncertain and probably multiple etiologies. Genetic
      predisposition to ASD may involve as many as 10 genes. Many experts believe that
      the abnormal brain development in autism occurs before 30 weeks' gestation in
      most instances. In utero rubella is a known cause of autism. Animal model data
      support the biologic plausibility that exposure to yet unrecognized infectious or
      other environmental agents could cause ASD. Several factors may contribute to
      apparent increases in incidence of ASD in recent years. Most data indicate
      increased recognition and reporting as primary factors, but the epidemiologic
      data are insufficient to determine if there has been a true increase in the
      incidence of ASD. Increased reporting of ASD in recent years has occurred long
      after the introduction of MMR vaccine in the United States in 1971 and widespread
      use of this vaccine in the 1970s for routine immunization of children at 12 to 15
      months of age. Appropriate detailed studies are needed to define the true
      incidence and prevalence of ASD. Epidemiologic studies in Europe indicate no
      association between MMR vaccine and ASD. Some children with ASD have
      gastrointestinal symptoms, but an increased rate of any specific gastrointestinal
      disorder in children with ASD has not been established. Studies to detect
      evidence of measles virus in intestinal tissue specimens from patients with IBD
      or autism with gastrointestinal symptoms have not used uniform techniques.
      Several laboratories have found no evidence of measles viruses in tissue
      specimens from patients with IBD, but 2 groups have found evidence of measles
      virus using different techniques. A group that found evidence of measles virus in
      affected tissue specimens from patients with IBD has also reported detecting
      portions of measles virus in peripheral blood lymphocytes and intestinal tissue
      specimens from patients with autism and gastrointestinal disorders. Finding a
      portion of a virus using molecular techniques does not constitute evidence for a
      causal relationship, because some viruses persist in unaffected hosts. Additional
      controlled studies in several laboratories are needed to determine if portions of
      measles virus persist in intestinal and other tissues of people with and without
      gastrointestinal disease and/or ASD. CONCLUSIONS: Although the possible
      association with MMR vaccine has received much public and political attention and
      there are many who have derived their own conclusions based on personal
      experiences, the available evidence does not support the hypothesis that MMR
      vaccine causes autism or associated disorders or IBD. Separate administration of
      measles, mumps, and rubella vaccines to children provides no benefit over
      administration of the combination MMR vaccine and would result in delayed or
      missed immunizations. Pediatricians need to work with families to ensure that
      children are protected early in the second year of life from these preventable
      diseases. Continued scientific efforts need to be directed to the identification
      of the causes of ASD.

PMID- 11331735
TI  - Technical report: the pediatrician's role in the diagnosis and management of
      autistic spectrum disorder in children.
AB  - Autism and its milder variants are not rare. Most pediatricians will have the
      opportunity to provide a medical home for a child with autism. This technical
      report serves to complement and expand on the information in the accompanying
      policy statement to increase the pediatrician's fund of knowledge and comfort
      level in caring for children with autism. In so doing, it is anticipated that
      earlier diagnosis and referral for appropriate intervention will be possible and
      that this will, in turn, have a positive effect on long-term outcomes for
      children with autism and their families.

PMID- 11331736
TI  - Type 2 diabetes mellitus in children and adolescents.

PMID- 11331737
TI  - Addressing environmentally caused human birth defects.

PMID- 11331738
TI  - Consultation with the specialist: liver transplantation for biliary atresia.

PMID- 11331739
TI  - Index of suspicion. Case 1. Diagnosis: intracranial hemorrhage.

PMID- 11331740
TI  - Degenerative central nervous system (CNS) disease.

PMID- 11331741
TI  - Evaluation of ataxia.

PMID- 11331743
TI  - Dissection of the ion-induced folding of the hammerhead ribozyme using 19F NMR.
AB  - We have used (19)F NMR to analyze the metal ion-induced folding of the hammerhead
      ribozyme by selective incorporation of 5fluorouridine. We have studied the
      chemical shift and linewidths of (19)F resonances of 5-fluorouridine at the 4 and
      7 positions in the ribozyme core as a function of added Mg(2+). The data fit well
      to a simple two-state model whereby the formation of domain 1 is induced by the
      noncooperative binding of Mg(2+) with an association constant in the range of 100
      to 500 M(-1), depending on the concentration of monovalent ions present. The
      results are in excellent agreement with data reporting on changes in the global
      shape of the ribozyme. However, the NMR experiments exploit reporters located in
      the center of the RNA sections undergoing the folding transitions, thereby
      allowing the assignment of specific nucleotides to the separate stages. The
      results define the folding pathway at high resolution and provide a time scale
      for the first transition in the millisecond range.

PMID- 11331744
TI  - Molecular dynamics of a grid-mounted molecular dipolar rotor in a rotating
      electric field.
AB  - Classical molecular dynamics is applied to the rotation of a dipolar molecular
      rotor mounted on a square grid and driven by rotating electric field E(nu) at T
      approximately 150 K. The rotor is a complex of Re with two substituted o
      phenanthrolines, one positively and one negatively charged, attached to an axial
      position of Rh(2)(4+) in a [2]staffanedicarboxylate grid through 2-(3
      cyanobicyclo[1.1.1]pent-1-yl)malonic dialdehyde. Four regimes are characterized
      by a, the average lag per turn: (i) synchronous (a < 1/e) at E(nu) = /E(nu)/ >
      E(c)(nu) [E(c)(nu) is the critical field strength], (ii) asynchronous (1/e < a <
      1) at E(c)(nu) > E(nu) > E(bo)(nu) > kT/mu;, [E(bo)(nu) is the break-off field
      strength], (iii) random driven (a approximately 1) at E(bo)(nu) > E(nu) > kT/mu,
      and (iv) random thermal (a approximately 1) at kT/mu > E(nu). A fifth regime, (v)
      strongly hindered, W > kT, E(mu), (W is the rotational barrier), has not been
      examined. We find E(bo)(nu)/kVcm(-1) approximately (kT/(mu))/kVcm(-1) +
      0.13(nu/GHz)(1.9) and E(c)(nu)/kVcm(-1) approximately (2.3kT/(mu))/kVcm(-1) +
      0.87(nu/GHz)(1.6). For nu > 40 GHz, the rotor behaves as a macroscopic body with
      a friction constant proportional to frequency, eta/eVps approximately 1.14
      nu/THz, and for nu < 20 GHz, it exhibits a uniquely molecular behavior.

PMID- 11331745
TI  - Tryptophan zippers: stable, monomeric beta -hairpins.
AB  - A structural motif, the tryptophan zipper (trpzip), greatly stabilizes the beta
      hairpin conformation in short peptides. Peptides (12 or 16 aa in length) with
      four different turn sequences are monomeric and fold cooperatively in water, as
      has been observed previously for some hairpin peptides. However, the folding free
      energies of the trpzips exceed substantially those of all previously reported
      beta-hairpins and even those of some larger designed proteins. NMR structures of
      three of the trpzip peptides reveal exceptionally well-defined beta-hairpin
      conformations stabilized by cross-strand pairs of indole rings. The trpzips are
      the smallest peptides to adopt an unique tertiary fold without requiring metal
      binding, unusual amino acids, or disulfide crosslinks.

PMID- 11331746
TI  - Proteomic dissection of dome formation in a mammary cell line: role of
      tropomyosin-5b and maspin.
AB  - In this work we extended the study of genes controlling the formation of specific
      differentiation structures called "domes" formed by the rat mammary
      adenocarcinoma cell line LA7 under the influence of DMSO. We have reported
      previously that an interferon-inducible gene, rat-8, and the beta-subunit of the
      epithelial sodium channel (ENaC) play a fundamental role in this process. Now, we
      used a proteomic approach to identify proteins differentially expressed either in
      DMSO-induced LA7 or in 106A10 cells. Two differentially expressed proteins were
      investigated. The first, tropomyosin-5b, strongly expressed in DMSO-induced LA7
      cells, is needed for dome formation because its synthesis inhibition by the
      antisense RNA technology abolished domes. The second protein, maspin, strongly
      expressed in the uninduced 106A10 cell line, inhibits dome formation because
      106A10 cells, transfected with rat8 cDNA (the function of which is required for
      the organization of these structures), acquired the ability to develop domes when
      cultured in presence of an antimaspin antibody. Dome formation in these cultures
      are accompanied by ENaC beta-subunit expression in the absence of DMSO.
      Therefore, dome formation requires the expression of tropomyosin-5b, in addition
      to the ENaC beta-subunit and the rat8 proteins, and is under the negative control
      of maspin.

PMID- 11331747
TI  - The crystal structure of a heptameric archaeal Sm protein: Implications for the
      eukaryotic snRNP core.
AB  - Sm proteins form the core of small nuclear ribonucleoprotein particles (snRNPs),
      making them key components of several mRNA-processing assemblies, including the
      spliceosome. We report the 1.75-A crystal structure of SmAP, an Sm-like archaeal
      protein that forms a heptameric ring perforated by a cationic pore. In addition
      to providing direct evidence for such an assembly in eukaryotic snRNPs, this
      structure (i) shows that SmAP homodimers are structurally similar to human Sm
      heterodimers, (ii) supports a gene duplication model of Sm protein evolution, and
      (iii) offers a model of SmAP bound to single-stranded RNA (ssRNA) that explains
      Sm binding-site specificity. The pronounced electrostatic asymmetry of the SmAP
      surface imparts directionality to putative SmAP-RNA interactions.

PMID- 11331748
TI  - Cardiac beta ARK1 inhibition prolongs survival and augments beta blocker therapy
      in a mouse model of severe heart failure.
AB  - Chronic human heart failure is characterized by abnormalities in beta-adrenergic
      receptor (betaAR) signaling, including increased levels of betaAR kinase 1
      (betaARK1), which seems critical to the pathogenesis of the disease. To determine
      whether inhibition of betaARK1 is sufficient to rescue a model of severe heart
      failure, we mated transgenic mice overexpressing a peptide inhibitor of betaARK1
      (betaARKct) with transgenic mice overexpressing the sarcoplasmic reticulum Ca(2+)
      binding protein, calsequestrin (CSQ). CSQ mice have a severe cardiomyopathy and
      markedly shortened survival (9 +/- 1 weeks). In contrast, CSQ/betaARKct mice
      exhibited a significant increase in mean survival age (15 +/- 1 weeks; P <
      0.0001) and showed less cardiac dilation, and cardiac function was significantly
      improved (CSQ vs. CSQ/betaARKct, left ventricular end diastolic dimension 5.60 +/
      0.17 mm vs. 4.19 +/- 0.09 mm, P < 0.005; % fractional shortening, 15 +/- 2 vs.
      36 +/- 2, P < 0.005). The enhancement of the survival rate in CSQ/betaARKct mice
      was substantially potentiated by chronic treatment with the betaAR antagonist
      metoprolol (CSQ/betaARKct nontreated vs. CSQ/betaARKct metoprolol treated, 15 +/-
      1 weeks vs. 25 +/- 2 weeks, P < 0.0001). Thus, overexpression of the betaARKct
      resulted in a marked prolongation in survival and improved cardiac function in a
      mouse model of severe cardiomyopathy that can be potentiated with beta-blocker
      therapy. These data demonstrate a significant synergy between an established
      heart-failure treatment and the strategy of betaARK1 inhibition.

PMID- 11331749
TI  - Changes in global gene expression patterns during development and maturation of
      the rat kidney.
AB  - We set out to define patterns of gene expression during kidney organogenesis by
      using high-density DNA array technology. Expression analysis of 8,740 rat genes
      revealed five discrete patterns or groups of gene expression during
      nephrogenesis. Group 1 consisted of genes with very high expression in the early
      embryonic kidney, many with roles in protein translation and DNA replication.
      Group 2 consisted of genes that peaked in midembryogenesis and contained many
      transcripts specifying proteins of the extracellular matrix. Many additional
      transcripts allied with groups 1 and 2 had known or proposed roles in kidney
      development and included LIM1, POD1, GFRA1, WT1, BCL2, Homeobox protein A11,
      timeless, pleiotrophin, HGF, HNF3, BMP4, TGF-alpha, TGF-beta2, IGF-II, met, FGF7,
      BMP4, and ganglioside-GD3. Group 3 consisted of transcripts that peaked in the
      neonatal period and contained a number of retrotransposon RNAs. Group 4 contained
      genes that steadily increased in relative expression levels throughout
      development, including many genes involved in energy metabolism and transport.
      Group 5 consisted of genes with relatively low levels of expression throughout
      embryogenesis but with markedly higher levels in the adult kidney; this group
      included a heterogeneous mix of transporters, detoxification enzymes, and
      oxidative stress genes. The data suggest that the embryonic kidney is committed
      to cellular proliferation and morphogenesis early on, followed sequentially by
      extracellular matrix deposition and acquisition of markers of terminal
      differentiation. The neonatal burst of retrotransposon mRNA was unexpected and
      may play a role in a stress response associated with birth. Custom analytical
      tools were developed including "The Equalizer" and "eBlot," which contain
      improved methods for data normalization, significance testing, and data mining.

PMID- 11331750
TI  - Glutamate antagonists limit tumor growth.
AB  - Neuronal progenitors and tumor cells possess propensity to proliferate and to
      migrate. Glutamate regulates proliferation and migration of neurons during
      development, but it is not known whether it influences proliferation and
      migration of tumor cells. We demonstrate that glutamate antagonists inhibit
      proliferation of human tumor cells. Colon adenocarcinoma, astrocytoma, and breast
      and lung carcinoma cells were most sensitive to the antiproliferative effect of
      the N-methyl-d-aspartate antagonist dizocilpine, whereas breast and lung
      carcinoma, colon adenocarcinoma, and neuroblastoma cells responded most favorably
      to the alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate antagonist
      GYKI52466. The antiproliferative effect of glutamate antagonists was Ca(2+)
      dependent and resulted from decreased cell division and increased cell death.
      Morphological alterations induced by glutamate antagonists in tumor cells
      consisted of reduced membrane ruffling and pseudopodial protrusions. Furthermore,
      glutamate antagonists decreased motility and invasive growth of tumor cells.
      These findings suggest anticancer potential of glutamate antagonists.

PMID- 11331751
TI  - Tomato Ve disease resistance genes encode cell surface-like receptors.
AB  - In tomato, Ve is implicated in race-specific resistance to infection by
      Verticillium species causing crop disease. Characterization of the Ve locus
      involved positional cloning and isolation of two closely linked inverted genes.
      Expression of individual Ve genes in susceptible potato plants conferred
      resistance to an aggressive race 1 isolate of Verticillium albo-atrum. The
      deduced primary structure of Ve1 and Ve2 included a hydrophobic N-terminal signal
      peptide, leucine-rich repeats containing 28 or 35 potential glycosylation sites,
      a hydrophobic membrane-spanning domain, and a C-terminal domain with the
      mammalian E/DXXXLphi or YXXphi endocytosis signals (phi is an amino acid with a
      hydrophobic side chain). A leucine zipper-like sequence occurs in the hydrophobic
      N-terminal signal peptide of Ve1 and a Pro-Glu-Ser-Thr (PEST)-like sequence
      resides in the C-terminal domain of Ve2. These structures suggest that the Ve
      genes encode a class of cell-surface glycoproteins with receptor-mediated
      endocytosis-like signals and leucine zipper or PEST sequences.

PMID- 11331752
TI  - Population maintenance among tropical reef fishes: inferences from small-island
      endemics.
AB  - To what extent do local populations of tropical reef fishes persist through the
      recruitment of pelagic larvae to their natal reef? Endemics from small, isolated
      islands can help answer that question by indicating whether special biological
      attributes are needed for long-term survival under enforced localization in high
      risk situations. Taxonomically and biologically, the endemics from seven such
      islands are broadly representative of their regional faunas. As natal-site
      recruitment occurs among reef fishes in much less isolated situations, these
      characteristics of island endemics indicate that a wide range of reef fishes
      could have persistent self-sustaining local populations. Because small islands
      regularly support substantial reef fish faunas, regional systems of small
      reserves could preserve much of the diversity of these fishes.

PMID- 11331753
TI  - A cardiac myocyte vascular endothelial growth factor paracrine pathway is
      required to maintain cardiac function.
AB  - The role of the cardiac myocyte as a mediator of paracrine signaling in the heart
      has remained unclear. To address this issue, we generated mice with cardiac
      myocyte-specific deletion of the vascular endothelial growth factor gene, thereby
      producing a cardiomyocyte-specific knockout of a secreted factor. The hearts of
      these mice had fewer coronary microvessels, thinned ventricular walls, depressed
      basal contractile function, induction of hypoxia-responsive genes involved in
      energy metabolism, and an abnormal response to beta-adrenergic stimulation. These
      findings establish the critical importance of cardiac myocyte-derived vascular
      endothelial growth factor in cardiac morphogenesis and determination of heart
      function. Further, they establish an adult murine model of hypovascular
      nonnecrotic cardiac contractile dysfunction.

PMID- 11331754
TI  - Construction of neocentromere-based human minichromosomes by telomere-associated
      chromosomal truncation.
AB  - Neocentromeres (NCs) are fully functional centromeres that arise ectopically in
      noncentromeric regions lacking alpha-satellite DNA. Using telomere-associated
      chromosome truncation, we have produced a series of minichromosomes (MiCs) from a
      mardel(10) marker chromosome containing a previously characterized human NC.
      These MiCs range in size from approximately 0.7 to 1.8 Mb and contain single-copy
      intact genomic DNA from the 10q25 region. Two of these NC-based Mi-Cs (NC-MiCs)
      appear circular whereas one is linear. All demonstrate stability in both
      structure and mitotic transmission in the absence of drug selection. Presence of
      a functional NC is shown by binding a host of key centromere-associated proteins.
      These NC-MiCs provide direct evidence for mitotic segregation function of the NC
      DNA and represent examples of stable mammalian MiCs lacking centromeric repeats.

PMID- 11331755
TI  - Linking osteopetrosis and pycnodysostosis: regulation of cathepsin K expression
      by the microphthalmia transcription factor family.
AB  - Various genetic conditions produce dysfunctional osteoclasts resulting in
      osteopetrosis or osteosclerosis. These include human pycnodysostosis, an
      autosomal recessive syndrome caused by cathepsin K mutation, cathepsin K
      deficient mice, and mitf mutant rodent strains. Cathepsin K is a highly expressed
      cysteine protease in osteoclasts that plays an essential role in the degradation
      of protein components of bone matrix. Cathepsin K also is expressed in a
      significant fraction of human breast cancers where it could contribute to tumor
      invasiveness. Mitf is a member of a helix-loop-helix transcription factor
      subfamily, which contains the potential dimerization partners TFE3, TFEB, and
      TFEC. In mice, dominant negative, but not recessive, mutations of mitf, produce
      osteopetrosis, suggesting a functional requirement for other family members. Mitf
      also has been found-and TFE3 has been suggested-to modulate age-dependent changes
      in osteoclast function. This study identifies cathepsin K as a transcriptional
      target of Mitf and TFE3 via three consensus elements in the cathepsin K promoter.
      Additionally, cathepsin K mRNA and protein were found to be deficient in mitf
      mutant osteoclasts, and overexpression of wild-type Mitf dramatically up
      regulated expression of endogenous cathepsin K in cultured human osteoclasts.
      Cathepsin K promoter activity was disrupted by dominant negative, but not
      recessive, mouse alleles of mitf in a pattern that closely matches their
      osteopetrotic phenotypes. This relationship between cathepsin K and the Mitf
      family helps explain the phenotypic overlap of their corresponding deficiencies
      in pycnodysostosis and osteopetrosis and identifies likely regulators of
      cathepsin K expression in bone homeostasis and human malignancy.

PMID- 11331756
TI  - A power law for cells.
AB  - Darwin observed that multiple, lowly organized, rudimentary, or exaggerated
      structures show increased relative variability. However, the cellular basis for
      these laws has never been investigated. Some animals, such as the nematode
      Caenorhabditis elegans, are famous for having organs that possess the same number
      of cells in all individuals, a property known as eutely. But for most
      multicellular creatures, the extent of cell number variability is unknown. Here
      we estimate variability in organ cell number for a variety of animals, plants,
      slime moulds, and volvocine algae. We find that the mean and variance in cell
      number obey a power law with an exponent of 2, comparable to Taylor's law in
      ecological processes. Relative cell number variability, as measured by the
      coefficient of variation, differs widely across taxa and tissues, but is
      generally independent of mean cell number among homologous tissues of closely
      related species. We show that the power law for cell number variability can be
      explained by stochastic branching process models based on the properties of cell
      lineages. We also identify taxa in which the precision of developmental control
      appears to have evolved. We propose that the scale independence of relative cell
      number variability is maintained by natural selection.

PMID- 11331757
TI  - SNARE proteins are highly enriched in lipid rafts in PC12 cells: implications for
      the spatial control of exocytosis.
AB  - Lipid rafts are microdomains present within membranes of most cell types. These
      membrane microdomains, which are enriched in cholesterol and glycosphingolipids,
      have been implicated in the regulation of certain signal transduction and
      membrane traffic pathways. To investigate the possibility that lipid rafts
      organize exocytotic pathways in neuroendocrine cells, we examined the association
      of proteins of the exocytotic machinery with rafts purified from PC12 cells. The
      target soluble N-ethylmaleimide-sensitive factor attachment protein receptor
      (tSNARE) proteins syntaxin 1A and synaptosomal-associated protein of 25 kDa (SNAP
      25) were both found to be highly enriched in lipid rafts ( approximately 25
      fold). The vesicle SNARE vesicle-associated membrane protein (VAMP)2 was also
      present in raft fractions, but the extent of this recovery was variable. However,
      further analysis revealed that the majority of VAMP2 was associated with a
      distinct class of raft with different detergent solubility characteristics to the
      rafts containing syntaxin 1A and SNAP-25. Interestingly, no other studied
      secretory proteins were significantly associated with lipid rafts, including
      SNARE effector proteins such as nSec1. Chemical crosslinking experiments showed
      that syntaxin1A/SNAP-25 heterodimers were equally present in raft and nonraft
      fractions, whereas syntaxin1A/nSec1 complexes were detected only in nonraft
      fractions. SDS-resistance assays revealed that raft-associated syntaxin1A/SNAP-25
      heterodimers were able to interact with VAMP2. Finally, reduction of cellular
      cholesterol levels decreased the extent of regulated exocytosis of dopamine from
      PC12 cells. The results described suggest that the interaction of SNARE proteins
      with lipid rafts is important for exocytosis and may allow structural and spatial
      organization of the secretory machinery.

PMID- 11331758
TI  - The HMG-domain protein BAP111 is important for the function of the BRM chromatin
      remodeling complex in vivo.
AB  - The Drosophila trithorax group gene brahma (brm) encodes the ATPase subunit of a
      SWI/SNF-like chromatin-remodeling complex. A key question about chromatin
      remodeling complexes is how they interact with DNA, particularly in the large
      genomes of higher eukaryotes. Here, we report the characterization of BAP111, a
      BRM-associated protein that contains a high mobility group (HMG) domain predicted
      to bind distorted or bent DNA. The presence of an HMG domain in BAP111 suggests
      that it may modulate interactions between the BRM complex and chromatin. BAP111
      is an abundant nuclear protein that is present in all cells throughout
      development. By using gel filtration chromatography and immunoprecipitation
      assays, we found that the majority of BAP111 protein in embryos is associated
      with the BRM complex. Furthermore, heterozygosity for BAP111 enhanced the
      phenotypes resulting from a partial loss of brm function. These data demonstrate
      that the BAP111 subunit is important for BRM complex function in vivo.

PMID- 11331759
TI  - Evolution of vertebrate steroid receptors from an ancestral estrogen receptor by
      ligand exploitation and serial genome expansions.
AB  - The evolution of novelty in tightly integrated biological systems, such as
      hormones and their receptors, seems to challenge the theory of natural selection:
      it has not been clear how a new function for any one part (such as a ligand) can
      be selected for unless the other members of the system (e.g., a receptor) are
      already present. Here I show-based on identification and phylogenetic analysis of
      steroid receptors in basal vertebrates and reconstruction of the sequences and
      functional attributes of ancestral proteins-that the first steroid receptor was
      an estrogen receptor, followed by a progesterone receptor. Genome mapping and
      phylogenetic analyses indicate that the full complement of mammalian steroid
      receptors evolved from these ancient receptors by two large-scale genome
      expansions, one before the advent of jawed vertebrates and one after. Specific
      regulation of physiological processes by androgens and corticoids are relatively
      recent innovations that emerged after these duplications. These findings support
      a model of ligand exploitation in which the terminal ligand in a biosynthetic
      pathway is the first for which a receptor evolves; selection for this hormone
      also selects for the synthesis of intermediates despite the absence of receptors,
      and duplicated receptors then evolve affinity for these substances. In this way,
      novel hormone-receptor pairs are created, and an integrated system of increasing
      complexity elaborated. This model suggests that ligands for some "orphan"
      receptors may be found among intermediates in the synthesis of ligands for
      phylogenetically related receptors.

PMID- 11331760
TI  - Comprehensive copy number and gene expression profiling of the 17q23 amplicon in
      human breast cancer.
AB  - The biological significance of DNA amplification in cancer is thought to be due
      to the selection of increased expression of a single or few important genes.
      However, systematic surveys of the copy number and expression of all genes within
      an amplified region of the genome have not been performed. Here we have used a
      combination of molecular, genomic, and microarray technologies to identify target
      genes for 17q23, a common region of amplification in breast cancers with poor
      prognosis. Construction of a 4-Mb genomic contig made it possible to define two
      common regions of amplification in breast cancer cell lines. Analysis of 184
      primary breast tumors by fluorescence in situ hybridization on tissue microarrays
      validated these results with the highest amplification frequency (12.5%) observed
      for the distal region. Based on GeneMap'99 information, 17 known genes and 26
      expressed sequence tags were localized to the contig. Analysis of genomic
      sequence identified 77 additional transcripts. A comprehensive analysis of
      expression levels of these transcripts in six breast cancer cell lines was
      carried out by using complementary DNA microarrays. The expression patterns
      varied from one cell line to another, and several overexpressed genes were
      identified. Of these, RPS6KB1, MUL, APPBP2, and TRAP240 as well as one
      uncharacterized expressed sequence tag were located in the two common amplified
      regions. In summary, comprehensive analysis of the 17q23 amplicon revealed a
      limited number of highly expressed genes that may contribute to the more
      aggressive clinical course observed in breast cancer patients with 17q23
      amplified tumors.

PMID- 11331761
TI  - Structure of melanoma inhibitory activity protein, a member of a recently
      identified family of secreted proteins.
AB  - Melanoma inhibitory activity (MIA) is a 12-kDa protein that is secreted from both
      chondrocytes and malignant melanoma cells. MIA has been reported to have effects
      on cell growth and adhesion, and it may play a role in melanoma metastasis and
      cartilage development. We report the 1.4-A crystal structure of human MIA, which
      consists of an Src homology 3 (SH3)-like domain with N- and C-terminal extensions
      of about 20 aa. each. The N- and C-terminal extensions add additional structural
      elements to the SH3 domain, forming a previously undescribed fold. MIA is a
      representative of a recently identified family of proteins and is the first
      structure of a secreted protein with an SH3 subdomain. The structure also
      suggests a likely protein interaction site and suggests that, unlike conventional
      SH3 domains, MIA does not recognize polyproline helices.

PMID- 11331762
TI  - Homologous-pairing activity of the human DNA-repair proteins Xrcc3.Rad51C.
AB  - The human Xrcc3 protein is involved in the repair of damaged DNA through
      homologous recombination, in which homologous pairing is a key step. The Rad51
      protein is believed to be the only protein factor that promotes homologous
      pairing in recombinational DNA repair in mitotic cells. In the brain, however,
      Rad51 expression is extremely low, whereas XRCC3, a human homologue of
      Saccharomyces cerevisiae RAD57 that activates the Rad51-dependent homologous
      pairing with the yeast Rad55 protein, is expressed. In this study, a two-hybrid
      analysis conducted with the use of a human brain cDNA library revealed that the
      major Xrcc3-interacting protein is a Rad51 paralog, Rad51C/Rad51L2. The purified
      Xrcc3.Rad51C complex, which shows apparent 1:1 stoichiometry, was found to
      catalyze the homologous pairing. Although the activity is reduced, the Rad51C
      protein alone also catalyzed homologous pairing, suggesting that Rad51C is a
      catalytic subunit for homologous pairing. The DNA-binding activity of
      Xrcc3.Rad51C was drastically decreased in the absence of Xrcc3, indicating that
      Xrcc3 is important for the DNA binding of Xrcc3.Rad51C. Electron microscopic
      observations revealed that Xrcc3.Rad51C and Rad51C formed similar filamentous
      structures with circular single-stranded DNA.

PMID- 11331763
TI  - Structure of Hjc, a Holliday junction resolvase, from Sulfolobus solfataricus.
AB  - The 2.15-A structure of Hjc, a Holliday junction-resolving enzyme from the
      archaeon Sulfolobus solfataricus, reveals extensive structural homology with a
      superfamily of nucleases that includes type II restriction enzymes. Hjc is a
      dimer with a large DNA-binding surface consisting of numerous basic residues
      surrounding the metal-binding residues of the active sites. Residues critical for
      catalysis, identified on the basis of sequence comparisons and site-directed
      mutagenesis studies, are clustered to produce two active sites in the dimer,
      about 29 A apart, consistent with the requirement for the introduction of paired
      nicks in opposing strands of the four-way DNA junction substrate. Hjc displays
      similarity to the restriction endonucleases in the way its specific DNA-cutting
      pattern is determined but uses a different arrangement of nuclease subunits.
      Further structural similarity to a broad group of metal/phosphate-binding
      proteins, including conservation of active-site location, is observed. A high
      degree of conservation of surface electrostatic character is observed between Hjc
      and T4-phage endonuclease VII despite a complete lack of structural homology. A
      model of the Hjc-Holliday junction complex is proposed, based on the available
      functional and structural data.

PMID- 11331764
TI  - TFIIH action in transcription initiation and promoter escape requires distinct
      regions of downstream promoter DNA.
AB  - TFIIH is a multifunctional RNA polymerase II general initiation factor that
      includes two DNA helicases encoded by the Xeroderma pigmentosum complementation
      group B (XPB) and D (XPD) genes and a cyclin-dependent protein kinase encoded by
      the CDK7 gene. Previous studies have shown that the TFIIH XPB DNA helicase plays
      critical roles not only in transcription initiation, where it catalyzes ATP
      dependent formation of the open complex, but also in efficient promoter escape,
      where it suppresses arrest of very early RNA polymerase II elongation
      intermediates. In this report, we present evidence that ATP-dependent TFIIH
      action in transcription initiation and promoter escape requires distinct regions
      of the DNA template; these regions are well separated from the promoter region
      unwound by the XPB DNA helicase and extend, respectively, approximately 23-39 and
      approximately 39-50 bp downstream from the transcriptional start site. Taken
      together, our findings bring to light a role for promoter DNA in TFIIH action and
      are consistent with the model that TFIIH translocates along promoter DNA ahead of
      the RNA polymerase II elongation complex until polymerase has escaped the
      promoter.

PMID- 11331765
TI  - Two enzymes of diacylglyceryl-O-4'-(N,N,N,-trimethyl)homoserine biosynthesis are
      encoded by btaA and btaB in the purple bacterium Rhodobacter sphaeroides.
AB  - Betaine lipids are ether-linked, nonphosphorous glycerolipids that resemble the
      more commonly known phosphatidylcholine in overall structure. Betaine lipids are
      abundant in many eukaryotes such as nonseed plants, algae, fungi, and amoeba.
      Some of these organisms are entirely devoid of phosphatidylcholine and, instead,
      contain a betaine lipid such as diacylglyceryl-O-4'-(N,N,N,-trimethyl)homoserine.
      Recently, this lipid also was discovered in the photosynthetic purple bacterium
      Rhodobacter sphaeroides where it seems to replace phosphatidylcholine under
      phosphate-limiting growth conditions. This discovery provided the opportunity to
      study the biosynthesis of betaine lipids in a bacterial model system. Mutants of
      R. sphaeroides deficient in the biosynthesis of the betaine lipid were isolated,
      and two genes essential for this process, btaA and btaB, were identified. It is
      proposed that btaA encodes an S-adenosylmethionine:diacylglycerol 3-amino-3
      carboxypropyl transferase and btaB an S-adenosylmethionine-dependent N
      methyltransferase. Both enzymatic activities can account for all reactions of
      betaine lipid head group biosynthesis. Because the equivalent reactions have been
      proposed for different eukaryotes, it seems likely that orthologs of btaA/btaB
      may be present in other betaine lipid-containing organisms.

PMID- 11331766
TI  - Trans-spliced leader addition to mRNAs in a cnidarian.
AB  - A search of databases with the sequence from the 5' untranslated region of a
      Hydra cDNA clone encoding a receptor protein-tyrosine kinase revealed that a
      number of Hydra cDNAs contain one of two different sequences at their 5' ends.
      This finding suggested the possibility that mRNAs in Hydra receive leader
      sequences by trans-splicing. This hypothesis was confirmed by the finding that
      the leader sequences are transcribed as parts of small RNAs encoded by genes
      located in the 5S rRNA clusters of Hydra. The two spliced leader (SL) RNAs (SL-A
      and -B) contain splice donor dinucleotides at the predicted positions, and genes
      that receive SLs contain splice acceptor dinucleotides at the predicted
      positions. Both of the SL RNAs are bound by antibody against trimethylguanosine,
      suggesting that they contain a trimethylguanosine cap. The predicted secondary
      structures of the Hydra SL RNAs show significant differences from the structures
      predicted for the SLs of other organisms. Messenger RNAs have been identified
      that can receive either SL-A or -B, although the impact of the two different SLs
      on the function of the mRNA is unknown. The presence and features of SL addition
      in the phylum Cnidaria raise interesting questions regarding the evolution of
      this process.

PMID- 11331767
TI  - Selective adsorption of L- and D-amino acids on calcite: Implications for
      biochemical homochirality.
AB  - The emergence of biochemical homochirality was a key step in the origin of life,
      yet prebiotic mechanisms for chiral separation are not well constrained. Here we
      demonstrate a geochemically plausible scenario for chiral separation of amino
      acids by adsorption on mineral surfaces. Crystals of the common rock-forming
      mineral calcite (CaCO(3)), when immersed in a racemic aspartic acid solution,
      display significant adsorption and chiral selectivity of d- and l-enantiomers on
      pairs of mirror-related crystal-growth surfaces. This selective adsorption is
      greater on crystals with terraced surface textures, which indicates that d- and l
      aspartic acid concentrate along step-like linear growth features. Thus, selective
      adsorption of linear arrays of d- and l-amino acids on calcite, with subsequent
      condensation polymerization, represents a plausible geochemical mechanism for the
      production of homochiral polypeptides on the prebiotic Earth.

PMID- 11331768
TI  - Mirror self-recognition in the bottlenose dolphin: a case of cognitive
      convergence.
AB  - The ability to recognize oneself in a mirror is an exceedingly rare capacity in
      the animal kingdom. To date, only humans and great apes have shown convincing
      evidence of mirror self-recognition. Two dolphins were exposed to reflective
      surfaces, and both demonstrated responses consistent with the use of the mirror
      to investigate marked parts of the body. This ability to use a mirror to inspect
      parts of the body is a striking example of evolutionary convergence with great
      apes and humans.

PMID- 11331769
TI  - BMP2-mediated alteration in the developmental pathway of fetal mouse brain cells
      from neurogenesis to astrocytogenesis.
AB  - We show that when telencephalic neural progenitors are briefly exposed to bone
      morphogenetic protein 2 (BMP2) in culture, their developmental fate is changed
      from neuronal cells to astrocytic cells. BMP2 significantly reduced the number of
      cells expressing microtubule-associated protein 2, a neuronal marker, and cells
      expressing nestin, a marker for undifferentiated neural precursors, but BMP2
      increased the number of cells expressing S100-beta, an astrocytic marker. In
      telencephalic neuroepithelial cells, BMP2 up-regulated the expression of negative
      helix-loop-helix (HLH) factors Id1, Id3, and Hes-5 (where Hes is homologue of
      hairy and Enhancer of Split) that inhibited the transcriptional activity of
      neurogenic HLH transcription factors Mash1 and neurogenin. Ectopic expression of
      either Id1 or Id3 (where Id is inhibitor of differentiation) inhibited
      neurogenesis of neuroepithelial cells, suggesting an important role for these HLH
      proteins in the BMP2-mediated changes in the neurogenic fate of these cells.
      Because gliogenesis in the brain and spinal cord, derived from implanted neural
      stem cells or induced by injury, is responsible for much of the failure of
      neuronal regeneration, this work may lead to a therapeutic strategy to minimize
      this problem.

PMID- 11331770
TI  - Low IGF-I suppresses VEGF-survival signaling in retinal endothelial cells: direct
      correlation with clinical retinopathy of prematurity.
AB  - Retinopathy of prematurity is a blinding disease, initiated by lack of retinal
      vascular growth after premature birth. We show that lack of insulin-like growth
      factor I (IGF-I) in knockout mice prevents normal retinal vascular growth,
      despite the presence of vascular endothelial growth factor, important to vessel
      development. In vitro, low levels of IGF-I prevent vascular endothelial growth
      factor-induced activation of protein kinase B (Akt), a kinase critical for
      endothelial cell survival. Our results from studies in premature infants suggest
      that if the IGF-I level is sufficient after birth, normal vessel development
      occurs and retinopathy of prematurity does not develop. When IGF-I is
      persistently low, vessels cease to grow, maturing avascular retina becomes
      hypoxic and vascular endothelial growth factor accumulates in the vitreous. As
      IGF-I increases to a critical level, retinal neovascularization is triggered.
      These data indicate that serum IGF-I levels in premature infants can predict
      which infants will develop retinopathy of prematurity and further suggests that
      early restoration of IGF-I in premature infants to normal levels could prevent
      this disease.

PMID- 11331771
TI  - Proteinase inhibitors I and II from potatoes block UVB-induced AP-1 activity by
      regulating the AP-1 protein compositional patterns in JB6 cells.
AB  - Proteinase inhibitor I (Inh I) and proteinase inhibitor II (Inh II) from potato
      tubers are effective proteinase inhibitors of chymotrypsin and trypsin. Inh I and
      Inh II were shown to suppress irradiation-induced transformation in mouse embryo
      fibroblasts suggesting that they possess anticarcinogenic characteristics. We
      have previously demonstrated that Inh I and Inh II could effectively block UV
      irradiation-induced activation of transcription activator protein 1 (AP-1) in
      mouse JB6 epidermal cells, which mechanistically may explain their
      anticarcinogenic actions. In the present study, we investigated the effects of
      Inh I and Inh II on the expression and composition pattern of the AP-1 complex
      following stimulation by UV B (UVB) irradiation in the JB6 model. We found that
      Inh I and Inh II specifically inhibited UVB-induced AP-1, but not NFkappaB,
      activity in JB6 cells. Both Inh I and Inh II up-regulated AP-1 constituent
      proteins, JunD and Fra-2, and suppressed c-Jun and c-Fos expression and
      composition in bound AP-1 in response to UVB stimulation. This regulation of the
      AP-1 protein compositional pattern in response to Inh I or Inh II may be critical
      for the inhibition of UVB-induced AP-1 activity by these agents found in
      potatoes.

PMID- 11331772
TI  - Phenotypic consequences of lung-specific inducible expression of FGF-3.
AB  - Members of the fibroblast growth factor (FGF) family play a critical role in
      embryonic lung development and adult lung physiology. The in vivo investigation
      of the role FGFs play in the adult lung has been hampered because the
      constitutive pulmonary expression of these factors often has deleterious effects
      and frequently results in neonatal lethality. To circumvent these shortcomings,
      we expressed FGF-3 in the lungs under the control of the progesterone antagonist
      responsive binary transgenic system. Four binary transgenic lines were obtained
      that showed ligand-dependent induction of FGF-3 with induced levels of FGF-3
      expression dependent on the levels of expression of the GLp65 regulator as well
      as the dose of the progesterone antagonist, RU486, administered. FGF-3 expression
      in the adult mouse lung resulted in two phenotypes depending on the levels of
      induction of FGF-3. Low levels of FGF-3 expression resulted in massive free
      alveolar macrophage infiltration. High levels of FGF-3 expression resulted in
      diffuse alveolar type II cell hyperplasia. Both phenotypes were reversible after
      the withdrawal of RU486. This system will be a valuable means of investigating
      the diverse roles of FGFs in the adult lung.

PMID- 11331773
TI  - A neural correlate of syntactic encoding during speech production.
AB  - Spoken language is one of the most compact and structured ways to convey
      information. The linguistic ability to structure individual words into larger
      sentence units permits speakers to express a nearly unlimited range of meanings.
      This ability is rooted in speakers' knowledge of syntax and in the corresponding
      process of syntactic encoding. Syntactic encoding is highly automatized, operates
      largely outside of conscious awareness, and overlaps closely in time with several
      other processes of language production. With the use of positron emission
      tomography we investigated the cortical activations during spoken language
      production that are related to the syntactic encoding process. In the paradigm of
      restrictive scene description, utterances varying in complexity of syntactic
      encoding were elicited. Results provided evidence that the left Rolandic
      operculum, caudally adjacent to Broca's area, is involved in both sentence-level
      and local (phrase-level) syntactic encoding during speaking.

PMID- 11331774
TI  - Hybrid vigor, fetal overgrowth, and viability of mice derived by nuclear cloning
      and tetraploid embryo complementation.
AB  - To assess whether heterozygosity of the donor cell genome was a general parameter
      crucial for long-term survival of cloned animals, we tested the ability of
      embryonic stem (ES) cells with either an inbred or F(1) genetic background to
      generate cloned mice by nuclear transfer. Most clones derived from five F(1) ES
      cell lines survived to adulthood. In contrast, clones from three inbred ES cell
      lines invariably died shortly after birth due to respiratory failure. Comparison
      of mice derived from nuclear cloning, in which a complete blastocyst is derived
      from a single ES cell, and tetraploid blastocyst complementation, in which only
      the inner cell mass is formed from a few injected ES cells, allows us to
      determine which phenotypes depend on the technique or on the characteristics of
      the ES cell line. Neonatal lethality also has been reported in mice entirely
      derived from inbred ES cells that had been injected into tetraploid blastocysts
      (ES cell-tetraploids). Like inbred clones, ES cell-tetraploid pups derived from
      inbred ES cell lines died shortly after delivery with signs of respiratory
      distress. In contrast, most ES cell-tetraploid neonates, derived from six F(1) ES
      cell lines, developed into fertile adults. Cloned pups obtained from both inbred
      and F(1) ES cell nuclei frequently displayed increased placental and birth
      weights whereas ES cell-tetraploid pups were of normal weight. The potency of
      F(1) ES cells to generate live, fertile adults was not lost after either long
      term in vitro culture or serial gene targeting events. We conclude that genetic
      heterozygosity is a crucial parameter for postnatal survival of mice that are
      entirely derived from ES cells by either nuclear cloning or tetraploid embryo
      complementation. In addition, our results demonstrate that tetraploid embryo
      complementation using F(1) ES cells represents a simple, efficient procedure for
      deriving animals with complex genetic alterations without the need for a chimeric
      intermediate.

PMID- 11331775
TI  - The chaperone GroEL is required for the final assembly of the molybdenum-iron
      protein of nitrogenase.
AB  - It is known that an E146D site-directed variant of the Azotobacter vinelandii
      iron protein (Fe protein) is specifically defective in its ability to participate
      in iron-molybdenum cofactor (FeMoco) insertion. Molybdenum-iron protein (MoFe
      protein) from the strain expressing the E146D Fe protein is partially (
      approximately 45%) FeMoco deficient. The "free" FeMoco that is not inserted
      accumulates in the cell. We were able to insert this "free" FeMoco into the
      partially pure FeMoco-deficient MoFe protein. This insertion reaction required
      crude extract of the DeltanifHDK A. vinelandii strain CA12, Fe protein and MgATP.
      We used this as an assay to purify a required "insertion" protein. The purified
      protein was identified as GroEL, based on the molecular mass of its subunit (58.8
      kDa), crossreaction with commercially available antibodies raised against E. coli
      GroEL, and its NH(2)-terminal polypeptide sequence. The NH(2)-terminal
      polypeptide sequence showed identity of up to 84% to GroEL from various
      organisms. Purified GroEL of A. vinelandii alone or in combination with MgATP and
      Fe protein did not support the FeMoco insertion into pure FeMoco-deficient MoFe
      protein, suggesting that there are still other proteins and/or factors missing.
      By using GroEL-containing extracts from a DeltanifHDK strain of A. vinelandii
      CA12 along with FeMoco, Fe protein, and MgATP, we were able to supply all
      required proteins and/or factors and obtained a fully active reconstituted E146D
      nifH MoFe protein. The involvement of the molecular chaperone GroEL in the
      insertion of a metal cluster into an apoprotein may have broad implications for
      the maturation of other metalloenzymes.

PMID- 11331776
TI  - Growth factor treatment enhances vestibular hair cell renewal and results in
      improved vestibular function.
AB  - The vestibules of adult guinea pigs were lesioned with gentamicin and then
      treated with perilymphatic infusion of either of two growth factor mixtures
      (i.e., GF I or GF II). GF I contained transforming growth factor alpha
      (TGFalpha), insulin-like growth factor type one (IGF-1), and retinoic acid (RA),
      whereas GF II contained those three factors and brain-derived neurotrophic
      factor. Treatment with GF I significantly enhanced vestibular hair cell renewal
      in ototoxin-damaged utricles and the maturation of stereociliary bundle
      morphology. The addition of brain-derived neurotrophic factor to the GF II
      infusion mixture resulted in the return of type 1 vestibular hair cells in
      ototoxin-damaged cristae, and improved vestibular function. These results suggest
      that growth factor therapy may be an effective treatment for balance disorders
      that are the result of hair cell dysfunction and/or loss.

PMID- 11331777
TI  - Differential fluorescence labeling of cysteinyl clusters uncovers high tissue
      levels of thionein.
AB  - The isolation of thionein (T) from tissues has not been reported heretofore. T
      contains 20 cysteinyl residues that react with 7-fluorobenz-2-oxa-1,3-diazole-4
      sulfonamide to form fluorescent adducts. In metallothionein (MT) the cysteinyl
      residues, which are bound to zinc, do not react. However, they do react in the
      presence of a chelating agent such as EDTA. The resultant difference in chemical
      reactivity provides a means to measure T in the absence of EDTA, (MT + T) in its
      presence, and, of course, MT by difference. The 7-fluorobenz-2-oxa-1,3-diazole-4
      sulfonamide derivative of T can be isolated from tissue homogenates by HPLC and
      quantified fluorimetrically with a detection limit in the femtomolar range and a
      linear response over 3 orders of magnitude. Analysis of liver, kidney, and brain
      of rats reveals almost as much T as MT. Moreover, in contrast to earlier views,
      MT in tissue extracts appears to be less stable than T. The existence of T in
      tissues under normal physiological conditions has important implications for its
      function both in zinc metabolism and the redox balance of the cell.

PMID- 11331778
TI  - A maize cytokinin gene encoding an O-glucosyltransferase specific to cis-zeatin.
AB  - Zeatin is a naturally occurring cytokinin. Biosynthesis and metabolism studies of
      zeatin have been directed mostly at the trans isomer, although cis-zeatin and its
      riboside occur as major components in some plant species. It is not known whether
      parallel regulatory pathways exist for the two isomers. Based on the sequence of
      the gene ZOG1 encoding a trans-zeatin O-glucosyltransferase from Phaseolus (EC ),
      a cis-zeatin-specific O-glucosyltransferase was isolated from maize. This gene,
      cisZOG1, contains an ORF of 1,401 nucleotides encoding a protein of 51.1 kDa with
      41% identity to the Phaseolus ZOG1 protein. Unexpectedly, the maize enzyme
      recognizes as substrates cis-zeatin and UDP-glucose but not cis-ribosylzeatin,
      trans-zeatin, or trans-ribosylzeatin. This finding indicates the existence of cis
      specific regulatory elements in plants and suggests that cis-zeatin and
      derivatives may be more important in cytokinin homeostasis than currently
      recognized.

PMID- 11331780
TI  - Mice lacking DNA topoisomerase IIIbeta develop to maturity but show a reduced
      mean lifespan.
AB  - Targeted gene disruption in the murine TOP3beta gene-encoding DNA topoisomerase
      IIIbeta was carried out. In contrast to the embryonic lethality of mutant mice
      lacking DNA topoisomerase IIIalpha, top3beta(-/-) nulls are viable and grow to
      maturity with no apparent defects. Mice lacking DNA topoisomerase IIIbeta have a
      shorter life expectancy than their wild-type littermates, however. The mean
      lifespan of the top3beta(-/-) mice is about 15 months, whereas that of their wild
      type littermates is longer than 2 years. Mortality of the top3beta(-/-) nulls
      appears to correlate with lesions in multiple organs, including hypertrophy of
      the spleen and submandibular lymph nodes, glomerulonephritis, and perivascular
      infiltrates in various organs. Because the DNA topoisomerase III isozymes are
      likely to interact with helicases of the RecQ family, enzymes that include the
      determinants of human Bloom, Werner, and Rothmund-Thomson syndromes, the
      shortened lifespan of top3beta(-/-) mice points to the possibility that the DNA
      topoisomerase III isozymes might be involved in the pathogenesis of progeroid
      syndromes caused by defective RecQ helicases.

PMID- 11331781
TI  - Retraction.

PMID- 11331779
TI  - Ubc9 interacts with a nuclear localization signal and mediates nuclear
      localization of the paired-like homeobox protein Vsx-1 independent of SUMO-1
      modification.
AB  - Vsx-1 is a paired-like:CVC homeobox gene whose expression is linked to bipolar
      cell differentiation during zebrafish retinogenesis. We used a yeast two-hybrid
      screen to identify proteins interacting with Vsx-1 and isolated Ubc9, an enzyme
      that conjugates the small ubiquitin-like modifier SUMO-1. Despite its interaction
      with Ubc9, we show that Vsx-1 is not a substrate for SUMO-1 in COS-7 cells or in
      vitro. When a yeast two-hybrid assay is used, deletion analysis of the
      interacting domain on Vsx-1 shows that Ubc9 binds to a nuclear localization
      signal (NLS) at the NH(2) terminus of the homeodomain. In SW13 cells, Vsx-1
      localizes to the nucleus and is excluded from nucleoli. Deletion of the NLS
      disrupts this nuclear localization, resulting in a diffuse cytoplasmic
      distribution of Vsx-1. In SW13 AK1 cells that express low levels of endogenous
      Ubc9, Vsx-1 accumulates in a perinuclear ring and colocalizes with an endoplasmic
      reticulum marker. However, NLS-tagged STAT1 protein exhibits normal nuclear
      localization in both SW13 and SW13 AK1 cells, suggesting that nuclear import is
      not globally disrupted. Cotransfection of Vsx-1 with Ubc9 restores Vsx-1 nuclear
      localization in SW3 AK1 cells and demonstrates that Ubc9 is required for the
      nuclear localization of Vsx-1. Ubc9 continues to restore nuclear localization
      even after a C93S active site mutation has eliminated its SUMO-1-conjugating
      ability. These results suggest that Ubc9 mediates the nuclear localization of Vsx
      1, and possibly other proteins, through a nonenzymatic mechanism that is
      independent of SUMO-1 conjugation.

PMID- 11331782
TI  - Granzymes A and B directly cleave lamins and disrupt the nuclear lamina during
      granule-mediated cytolysis.
AB  - Cytotoxic T lymphocytes (CTL) induce apoptosis by engaging death receptors or by
      exocytosis of cytolytic granules containing granzyme (Gzm) proteases and
      perforin. The lamins, which maintain the structural integrity of the nuclear
      envelope, are cleaved by caspases during caspase-mediated apoptosis. Although
      death receptor engagement and GzmB activate caspases, CTL also induce apoptosis
      during caspase blockade. Both GzmA and GzmB directly and efficiently cleave
      laminB in vitro, in situ in isolated nuclei and in cells loaded with perforin and
      Gzms, even in the presence of caspase inhibitors. LaminB is cleaved by GzmA at
      concentrations of 3 nM, but GzmB is 50 times less active. GzmA cuts laminB at
      R392; GzmB cuts at the caspase VEVD231 site. Characteristic laminB fragments
      generated by Gzm proteolysis also are observed during CTL lysis, even in the
      presence of caspase inhibitors or in cells overexpressing bcl-2. Lamins A/C are
      direct substrates of GzmA, but not GzmB. GzmA and GzmB therefore directly target
      critical caspase substrates in caspase-resistant cells.

PMID- 11331783
TI  - Traumatic insemination and sexual conflict in the bed bug Cimex lectularius.
AB  - The bed bug, Cimex lectularius, has a unique mode of copulation termed
      "traumatic" insemination [Carayon, J. (1966) in Monograph of the Cimicidae, ed.
      Usinger, R. (Entomol. Soc. Am., Philadelphia), pp. 81-167] during which the male
      pierces the female's abdominal wall with his external genitalia and inseminates
      into her body cavity [Carayon, J. (1966) in Monograph of the Cimicidae, ed.
      Usinger, R. (Entomol. Soc. Am., Philadelphia), pp. 81-167]. Under controlled
      natural conditions, traumatic insemination was frequent and temporally
      restricted. We show for the first time, to our knowledge, that traumatic
      insemination results in (i) last-male sperm precedence, (ii) suboptimal remating
      frequencies for the maintenance of female fertility, and (iii) reduced longevity
      and reproductive success in females. Experimental females did not receive
      indirect benefits from multiple mating. We conclude that traumatic insemination
      is probably a coercive male copulatory strategy that results in a sexual conflict
      of interests.

PMID- 11331784
TI  - Hydrogen peroxide mediates the cell growth and transformation caused by the
      mitogenic oxidase Nox1.
AB  - Nox1, a homologue of gp91phox, the catalytic moiety of the superoxide (O(2)(-))
      generating NADPH oxidase of phagocytes, causes increased O(2)(-) generation,
      increased mitotic rate, cell transformation, and tumorigenicity when expressed in
      NIH 3T3 fibroblasts. This study explores the role of reactive oxygen species
      (ROS) in regulating cell growth and transformation by Nox1. H(2)O(2)
      concentration increased approximately 10-fold in Nox1-expressing cells, compared
      with <2-fold increase in O(2)(-). When human catalase was expressed in Nox1
      expressing cells, H(2)O(2) concentration decreased, and the cells reverted to a
      normal appearance, the growth rate normalized, and cells no longer produced
      tumors in athymic mice. A large number of genes, including many related to cell
      cycle, growth, and cancer (but unrelated to oxidative stress), were expressed in
      Nox1-expressing cells, and more than 60% of these returned to normal levels on
      coexpression of catalase. Thus, H(2)O(2) in low concentrations functions as an
      intracellular signal that triggers a genetic program related to cell growth.

PMID- 11331785
TI  - Comparison of the early stages of forced unfolding for fibronectin type III
      modules.
AB  - The structural changes accompanying stretch-induced early unfolding events were
      investigated for the four type III fibronectin (FN-III) modules, FN-III(7), FN
      III(8), FN-III(9), and FN-III(10) by using steered molecular dynamics.
      Simulations revealed that two main energy barriers, I and II, have to be overcome
      to initiate unraveling of FN-III's tertiary structure. In crossing the first
      barrier, the two opposing beta-sheets of FN-III are rotated against each other
      such that the beta-strands of both beta-sheets align parallel to the force vector
      (aligned state). All further events in the unfolding pathway proceed from this
      intermediate state. A second energy barrier has to be overcome to break the first
      major cluster of hydrogen bonds between adjacent beta-strands. Simulations
      revealed that the height of barrier I varied significantly among the four modules
      studied, being largest for FN-III(7) and lowest for FN-III(10), whereas the
      height of barrier II showed little variation. Key residues affecting the
      mechanical stability of FN-III modules were identified. These results suggest
      that FN-III modules can be prestretched into an intermediate state with only
      minor changes to their tertiary structures. FN-III(10), for example, extends 12 A
      from the native "twisted" to the intermediate aligned state, and an additional 10
      A from the aligned state to further unfolding where the first beta-strand is
      peeled away. The implications of the existence of intermediate states regarding
      the elasticity of fibrillar fibers and the stretch-induced exposure of cryptic
      sites are discussed.

PMID- 11331786
TI  - A proven treatment for lack of insight.

PMID- 11331788
TI  - Consumer & family information: obsessive-compulsive disorder.

PMID- 11331789
TI  - Datapoints: are psychiatrists more dissatisfied with their careers than other
      physicians?

PMID- 11331790
TI  - Dissemination of educational classes for families of adults with schizophrenia.
AB  - Despite the well-documented efficacy of psychoeducational and behavioral
      approaches in family interventions for persons with serious mental illness (1),
      clinicians have rarely included these methods in their professional repertoires
      (2). Journal publications, books, continuing education courses, and advocacy by
      the National Alliance for the Mentally Ill and its local affiliates have induced
      few professionals to provide family psychoeducation. Mental health professionals
      adopt new services primarily for the same reason that employees of any firm
      change their work practices-namely, because the authority structure and
      contingencies of reinforcement that impinge on their daily activities are altered
      in a direction favoring change. Therefore, administrative clout must be brought
      to bear to mandate the inclusion of family psychoeducation in the spectrum of
      services provided by a clinic, mental health center, community support program,
      hospital, or independent provider (3). In addition, the consequences of
      clinicians' services must differentially reward the use of these methods of
      involving families in services for the seriously mentally ill (4). Differential
      rewards could come from performance standards and evaluations, performance-based
      pay, third-party payments, positive feedback from clients and families, public
      recognition, and increased self-efficacy. Use of in-service training or workshops
      to persuade clinicians to adopt innovations such as family psychoeducation and
      family management techniques has a checkered and unremarkable track record. For
      example, brief training has failed completely in efforts to bring about adoption
      of family interventions. On the other hand, more extended efforts to train staff,
      including organizational consultation, have been more successful (5). In one
      study, two days of staff training produced no change, whereas intensive training
      over several months resulted in the implementation of new family programs at the
      majority of study sites (6). Staff from sites that received extensive training
      but did not adopt the interventions rated family interventions as less consistent
      with their professional philosophy and agency norms and identified more obstacles
      to intervention, notably intense work pressure, uncertainty about financing the
      intervention, agency bureaucracy, lack of leadership, skepticism about the
      interventions, problems with confidentiality, and inability to provide services
      in the evenings or on weekends (6). In this Rehab Rounds column, Amenson and
      Liberman describe a three-phase, multilevel dissemination effort designed to
      overcome the above-mentioned barriers to the incorporation of family
      psychoeducation into the routine care provided at community mental health centers
      in an ethnically diverse urban setting. Moreover, Amenson and Liberman
      demonstrate the need for continued support and nurturance of the project to
      ensure that the original enthusiasm associated with a novel intervention is not
      lost once it becomes a standard part of treatment.

PMID- 11331791
TI  - Developing standards of care for individuals with co-occurring psychiatric and
      substance use disorders.

PMID- 11331792
TI  - The impact of withdrawals by Medicaid managed care plans on behavioral health
      services.

PMID- 11331793
TI  - Split treatment: the psychotherapy role of the prescribing psychiatrist.

PMID- 11331794
TI  - Cardiac effects of antipsychotic medications.

PMID- 11331795
TI  - Evidence-based pharmacologic treatment for people with severe mental illness: a
      focus on guidelines and algorithms.
AB  - Medication treatment of severe mental illness has been advanced and complicated
      by the introduction of numerous therapeutic agents. Practice guidelines based on
      research evidence have been developed to help clinicians make complex decisions.
      Studies of usual care suggest an important potential role for guidelines in
      improving the quality of medication treatment for people with severe mental
      illness. The authors review current evidence-based guidelines for medication
      treatment of persons with severe mental illness. Four categories of guidelines
      are described: recommendations, comprehensive treatment options, medication
      algorithms, and expert consensus. The authors note that more research is needed
      on optimal next-step strategies and the treatment of patients with comorbidity
      and other complicating problems. They discuss barriers to the implementation of
      guidelines, and they observe that the potential of guidelines and algorithms to
      promote evidence-based medication treatment for persons with severe mental
      illness depends on refinement of tools, progress in research, and cooperation of
      physicians, nonphysician clinicians, administrators, and consumers and family
      members.

PMID- 11331796
TI  - Mental illness and changing definitions of disability under the Americans With
      Disabilities Act.
AB  - The Americans With Disabilities Act (ADA) prohibits employment discrimination on
      the basis of disability. Originally, an assessment of whether a person had a
      disability and thus was protected by the ADA examined the person's impairment in
      its uncorrected state. Thus it was comparatively easy for people with mental
      illness to meet the threshold requirement for having a disability. However, in
      1999 the U.S. Supreme Court issued three decisions holding that, for the purposes
      of the ADA, disability had to be assessed in its corrected state. Since those
      decisions were issued, the courts have increased the burden on individuals,
      including people with mental illness, to prove that they have a disability. In
      several cases, courts ruled that people with serious mental illnesses do not have
      a disability and are not protected by the ADA. This article discusses these cases
      and their implications for people with mental illness and for practitioners.

PMID- 11331797
TI  - Case management and assertive community treatment in Europe.
AB  - OBJECTIVE: Case management studies from Europe and the United States continue to
      yield conflicting results. At a symposium at the World Psychiatric Conference in
      Hamburg in 1999, researchers from four European countries explored the possible
      reasons for differences in outcome. They also examined reasons for the differing
      foci of case management studies across the different cultures. The authors
      summarize the symposium's findings. METHODS: Individual case presentations were
      given of studies and services from the United Kingdom (three studies), Sweden
      (two studies), Germany, and Italy (one each). Outcomes, methodologies, and
      national service context were examined. RESULTS AND CONCLUSIONS: A significant
      influence of national culture is evident both in the acceptability of case
      management and in approaches to researching it. Case management is perceived as
      an "Anglophone import" in Italy but is now national policy for persons with
      severe mental illness in the other three countries. Studies from the United
      Kingdom emphasized methodological rigor, with little attention to treatment
      content, whereas those from Sweden accepted a less disruptive research approach
      but with a more prescriptive stipulation of treatment content. Studies from Italy
      and Germany emphasized the importance of differing descriptive methodologies.
      Marked differences in the range of social care provision were noted across
      Europe. Overall, European researchers are less concerned than U.S. researchers
      with studying the impact of case management on hospital use.

PMID- 11331798
TI  - An eight-year longitudinal comparison of clinical course and characteristics of
      social phobia among men and women.
AB  - OBJECTIVE: Social phobia is a chronic disorder with a higher prevalence among
      women than men. Data from an eight-year longitudinal study were analyzed to
      investigate the course of social phobia and to explore potential sex differences
      in the course and characteristics of the illness. METHODS: Data were analyzed
      from the Harvard/Brown Anxiety Research Program, a naturalistic, observational
      study begun in 1989 in which patients with social phobia are assessed every six
      to 12 months. Treatment was observed but not prescribed by the program personnel.
      Data on comorbidity, remission, and health-related quality of life were collected
      for 176 patients with social phobia. RESULTS: Only 38 percent of women and 32
      percent of men experienced a complete remission during the eight-year study
      period, a difference that was not significant. A larger proportion of women than
      men had the generalized form of social phobia, although the difference was not
      significant. Women were more likely to have concurrent agoraphobia, and men had a
      higher rate of comorbid substance use disorders. Social phobia had a more chronic
      course among women who had low Global Assessment of Functioning scores and a
      history of suicide attempts at baseline than among men who had these
      characteristics. Health-related quality of life was similar for both men and
      women, except that women were slightly but significantly more impaired in
      household functioning. CONCLUSIONS: The chronicity of social phobia was striking
      for both men and women. Although remission rates did not differ significantly
      between men and women, clinicians should be alert to the fact that women with
      poor baseline functioning and a history of suicide attempts have the greatest
      chronicity of illness.

PMID- 11331799
TI  - The EEOC charge priority policy and claimants with psychiatric disabilities.
AB  - OBJECTIVE: In June 1995 the U.S. Equal Employment Opportunity Commission (EEOC)
      instituted a new charge priority policy. Under the new policy, charges are
      classified as one of three priority levels during or immediately after intake.
      Only charges assigned a high priority receive a full investigation. This paper
      examines the effect of the charge priority policy on individuals with psychiatric
      disabilities who filed Americans With Disabilities Act (ADA) charges with the
      EEOC. METHODS: Using data extracted from the EEOC's charge data system, the
      authors analyzed all 66,298 ADA claims prioritized and closed between June 1995
      and March 1998. The z test for difference in proportions and the generalized
      estimating equations procedure were used. The primary outcome measure was the
      priority assignment received by ADA claimants. RESULTS: Charges that received a
      high priority assignment were more likely to result in benefits for claimants.
      Charges filed by claimants with psychiatric disabilities were significantly less
      likely to be assigned a high priority than charges filed by other claimants.
      Claimants with psychiatric disabilities were also significantly less likely to
      benefit from their claims. CONCLUSIONS: The strong relationship between being
      assigned high priority and receiving benefits as a result of filing a charge
      demonstrates the importance of accurate priority categorization. The finding that
      people with psychiatric disabilities are less likely than others to benefit from
      their claims is cause for concern, particularly given the fact that the accuracy
      of the charge prioritization system has not been validated.

PMID- 11331800
TI  - Engaging community mental health stakeholders in pharmacy cost management.
AB  - To improve the cost-effectiveness of psychotropic medications, a process was
      established to involve all stakeholders in a seven-county public-sector
      behavioral health managed care plan in the development of formulary guidelines.
      After delineation of the issues and of possible strategies, proposed formulary
      guidelines were drafted and presented to the stakeholders in a series of
      meetings. The stakeholders were also educated about pharmacy cost management
      issues and possible strategies. The guidelines were modified on the basis of the
      feedback obtained from stakeholders, and the consensus formulary guidelines were
      adopted. Within ten weeks of implementation of the guidelines, monthly medication
      costs had declined by 3 percent from baseline, although the number of medication
      users increased by 3 percent over the same period. There were few complaints
      about the guidelines. Effective, consensus-driven, medication cost-containment
      strategies can be implemented through a process of engagement and education of
      stakeholders in a community mental health plan.

PMID- 11331801
TI  - A public health perspective on violent offenses among persons with mental
      illness.
AB  - OBJECTIVE: This study reanalyzed existing data to assess the extent to which
      persons with mental illness might contribute to criminal violence in the
      community. METHODS: Data were examined from a representative sample of 1,151
      remanded offenders who underwent a full structured diagnostic interview that was
      used to provide one-month prevalence rates of mental illnesses as defined by the
      Structured Clincal Interview for DSM-III-R. Diagnoses of interest were mood,
      psychotic, anxiety, psychoactive substance use, adjustment, and miscellaneous
      axis I disorders and axis II personality disorders. Criminological data
      describing the number of offenses against persons and property and the number of
      victimless crimes were abstracted from police arrest reports and warrants. A
      violent crime was defined as any crime against a person. RESULTS: The one-month
      prevalence of major mental and substance use disorders of newly admitted inmates
      was 61 percent. About 3 percent of violent offenses could be attributed to
      individuals who had a principal diagnosis of any non-substance use-related
      disorder. An additional 7 percent of violent offenses could be attributed to
      individuals who had a primary diagnosis of a substance use disorder. CONCLUSIONS:
      The results of the study support the hypothesis that people with mental and
      substance use disorders are not major contributors to police-identified criminal
      violence. Public perceptions of mentally ill persons as criminally dangerous
      appear to be greatly exaggerated.

PMID- 11331802
TI  - The prevalence of religious coping among persons with persistent mental illness.
AB  - OBJECTIVE: The purpose of this study was to examine the prevalence of religious
      coping among persons with persistent mental illness and to gain a preliminary
      understanding of the relationship between religious coping and symptom severity
      and overall functioning. METHODS: A total of 406 individuals who were diagnosed
      as having a mental illness and who were patients at one of 13 Los Angeles County
      mental health facilities completed a survey consisting of the Religious Coping
      Index, the Symptom Checklist 90-R (SCL-90), the Global Assessment of Functioning
      (GAF) scale, and a 48-item demographic questionnaire. RESULTS: More than 80
      percent of the participants used religious beliefs or activities to cope with
      daily difficulties or frustrations. A majority of participants devoted as much as
      half of their total coping time to religious practices, with prayer being the
      most frequent activity. Specific religious coping strategies, such as prayer or
      reading the Bible, were associated with higher SCL-90 scores (indicating more
      severe symptoms), more reported frustration, and a lower GAF score (indicating
      greater impairment). The amount of time that participants devoted to religious
      coping was negatively related to reported levels of frustration and scores on the
      SCL-90 symptom subscales. CONCLUSIONS: The results of the study suggest that
      religious activities and beliefs may be particularly compelling for persons who
      are experiencing more severe symptoms, and increased religious activity may be
      associated with reduced symptoms. Religion may serve as a pervasive and
      potentially effective method of coping for persons with mental illness, thus
      warranting its integration into psychiatric and psychological practice.

PMID- 11331803
TI  - Variations in the treatment culture of nursing homes and responses to regulations
      to reduce drug use.
AB  - OBJECTIVE: The study examined the relationship between treatment cultures of
      nursing homes and their responses to regulations to reduce use of psychotropic
      drugs mandated by the 1987 Omnibus Budget Reconciliation ACT: The authors
      hypothesized that reduction in use of antipsychotic drugs was more likely to
      occur in homes with a resident-centered culture emphasizing psychosocial care,
      avoidance of psychotropic drugs, pharmacist feedback, and involvement of mental
      health workers. The authors also predicted greater reductions in drug use in
      facilities with a less severe case mix and better capacity for change. METHODS:
      Data were collected in a stratified random sample of 16 skilled nursing
      facilities in Wisconsin. Participants included 1,181 residents in the baseline
      study and 1,650 residents in the follow-up study. Treatment culture was measured
      with a questionnaire for assessing nurses' beliefs and philosophies of care and
      their interactions with pharmacists and mental health workers. RESULTS: No
      significant change was observed in the use of benzodiazepines, antidepressants,
      or polymedicine (two or more psychotropic medications). However, use of
      antipsychotic drugs decreased significantly, from 24 percent to 16 percent. The
      change in use varied dramatically across facilities, from an 85 percent reduction
      to a 19 percent increase. Findings also revealed significant variability in
      treatment cultures. Greater reductions in use of antipsychotic drugs were found
      in facilities with a resident-centered culture, a less severe case mix, and a
      higher nurse-to-resident staffing ratio. CONCLUSIONS: Future policy and quality
      improvement efforts must address treatment cultures, staffing, and other
      organizational barriers to nursing home reform.

PMID- 11331804
TI  - Maintaining quality of care in a comprehensive dual diagnosis treatment program.
AB  - This paper describes how a large, multifaceted dual diagnosis treatment program
      has attempted to preserve its mission through termination of or changes in the
      nature of resident research projects. Research reports, because of their focus on
      specific treatment components, often fail to capture the essence of the larger
      treatment contexts from which they emanate. Although host programs derive
      benefits from research projects, enhancements are often temporary and difficult
      to sustain. Programs are thus challenged to respond to resource losses
      creatively. The author discusses adaptations to losses in the areas of case
      management, behavioral skills training, an incentive system, money management,
      and continuity of care.

PMID- 11331805
TI  - Comparison of discharge rates and drug costs for patients with schizophrenia
      treated with risperidone or olanzapine.
AB  - This study compared the discharge rates and drug costs of 789 patients with
      schizophrenia or schizoaffective disorder who began pharmacotherapy with
      olanzapine or risperidone between July 1997 and June 1998. Discharge rates 30
      days after the start of treatment were 45 percent for the patients treated with
      risperidone and 32 percent for those treated with olanzapine (p=.001). Daily drug
      costs during the same period were $6.42 for risperidone and $12.29 for olanzapine
      (p<.001). For risperidone, lower dosages were associated with higher hospital
      discharge rates, whereas no significant association was observed for olanzapine.
      These data suggest that among inpatients with schizophrenia or schizoaffective
      disorder, use of risperidone results in a higher discharge rate and a lower drug
      cost than use of olanzapine.

PMID- 11331806
TI  - Knowledge about HIV transmission and prevention among Italian patients with
      psychiatric disorders.
AB  - For a study designed to examine the accuracy of information about HIV
      transmission, risk behavior, and preventive measures among individuals with
      psychiatric disorders in Italy, 214 psychiatric patients-114 outpatients and 100
      inpatients-and 88 nonpsychiatric patients completed the AIDS Risk Behavior
      Knowledge Test. Levels of knowledge were lower among psychiatric patients than
      among control subjects. Patients with chronic illness and a diagnosis of
      schizophrenia were found to have less knowledge than other patients about HIV
      transmission. These findings confirm the need for HIV-related educational and
      behavior-modification programs for patients with chronic and severe mental
      illness in the community in Italy.

PMID- 11331807
TI  - A cluster analysis of patients with schizophrenia in community care.
AB  - In a sample of patients with schizophrenia, four clusters were identified and
      service use and relatives' satisfaction analyzed. In the first cluster, patients'
      severity of illness was mild and their use of services low. In the second,
      patients' disability was more severe; psychiatric symptoms were low in severity,
      family burden was moderate, and use of community services was more intensive. In
      the third cluster, patients had serious disability and severe positive symptoms;
      their families suffered distressing burdens, and their use of hospital and
      community services was intensive. In the fourth cluster, patients' disability was
      very severe, negative symptoms were prominent, and relatives' burden was
      moderate; use of hospital services was frequent, and use of community services
      was less so.

PMID- 11331808
TI  - Autocastration as a presenting sign of incipient schizophrenia.
AB  - Previous case reports on autocastration have identified individuals who engaged
      in genital self-mutilation as being overtly psychotic, as having previously
      received a diagnosis of schizophrenia, or as having significant dysfunction of
      ego integrity, manifesting as guilt and low self-esteem. This paper describes a
      patient who had had no previous psychiatric symptoms or mental health treatment
      and for whom the act of autocastration was the first sign of incipient
      schizophrenia.

PMID- 11331810
TI  - Potential overdiagnosis of bipolar disorder.

PMID- 11331811
TI  - A conceptual model of recovery.

PMID- 11331813
TI  - Unanswered questions about telepsychiatry.

PMID- 11331814
TI  - Improving capacity assessments.

PMID- 11331815
TI  - The world gets smaller every day.

PMID- 11331817
TI  - Who pays when air medical personnel are injured?

PMID- 11331818
TI  - Hydrocarbon toxicity: General review and management guidelines.

PMID- 11331819
TI  - Flying with ice. Part 2.

PMID- 11331820
TI  - Air medical accidents involving collision with objects.

PMID- 11331821
TI  - Lifeliner One aloft in Amsterdam.

PMID- 11331822
TI  - Helicopter emergency medical service in Spain.
AB  - No studies had been conducted about Spanish HEMS programs, so we conducted a
      nationwide survey by phone from January to June 1999. We identified 18 HEMS
      programs in 13 regions, which transported 4870 patients in 1998. The
      primary/interhospital missions ratio was 51.25/48.75. In 78% of responding
      programs, the medical crew was a physician and a nurse. Only 33% of HEMS had
      standard medical equipment; most lacked noninvasive blood pressure monitors, and
      one-third of the medical personal were correctly protected with flight helmets
      and flight suits. It is necessary to study the cost-effectiveness of the Spanish
      model of HEMS.

PMID- 11331823
TI  - Experiences with transporting stretcher cases on long flights on commercial
      airlines.

PMID- 11331824
TI  - A rural ambulance helicopter system in northern Sweden.
AB  - INTRODUCTION: In Sweden, several ambulance helicopter programs have been used
      during the past 3 decades. This article describes one of these programs. SETTING:
      The catchment area of the helicopter system under study was a typical rural
      setting with a population density of less than 5 people per square kilometer.
      METHODS: We describe in detail, with special reference to medical aspects, the
      activities of an helicopter ambulance program in 1997. RESULTS: A total of 288
      missions, including 328 patients (204 men), were analyzed. Trauma cases (29%) and
      patients with cardiovascular (24%) and neurologic problems (13%) dominated the
      missions. One-sixth of the cases occurred at night. The median response time was
      12 minutes, and the median on-scene time was 28 minutes. The medical
      interventions performed included intubations; central venous catheter, arterial
      needle, and duodenal tube insertions; and medication administered intravenously,
      orally, and intrabronchially. CONCLUSION: We detected a higher rate of trauma
      cases than in previously published investigations, probably related to the
      outdoor activities of the area. We believe that the rapid institution of
      thrombolytic treatment in suspected acute myocardial infarction and a more rapid
      and flexible transport of trauma cases in a rural area are important. We estimate
      that, in most cases, the helicopter service could provide a quicker transport
      than a ground ambulance; however, for short distance transports, ground ambulance
      is faster than helicopter ambulance.

PMID- 11331825
TI  - Effects of ground EMS and ED personnel on air medical trauma on-site times.
AB  - INTRODUCTION: On-site times for helicopter EMS (HEMS) providers are hypothesized
      to increase when procedures indicated by national standards of care and local
      HEMS are not consistently completed by ground EMS (GEMS) or ED providers before
      HEMS arrival in trauma cases. METHODS: In this prospective study, we divided all
      trauma missions (120) flown by a university-based HEMS during a 3-month period
      into interfacility missions (between hospitals, ground providers are ED
      personnel) and scene missions (between scenes and hospitals, ground providers are
      GEMS). HEMS completed forms identifying which procedures were completed and
      omitted by GEMS or ED providers. We collected relevant times from county
      dispatchers and HEMS flight control. RESULTS: Ground providers frequently did not
      complete indicated basic and advanced procedures. A relationship existed between
      scene GEMS omissions and HEMS on-site times. If no procedures were omitted,
      average HEMS time on-site was 13 minutes, increasing to 17 minutes for one
      procedure omitted and 20 minutes for two or more. No relationship was found on
      interfacility missions between ED provider omissions and HEMS on-site times.
      However, any existing effect may have been eclipsed by external factors
      significantly extending HEMS on-site times (mean 43 minutes). An average of 93
      minutes elapsed between the request for HEMS transport and patient arrival at the
      transferring hospital. CONCLUSION: GEMS frequently omit indicated procedures. For
      scene missions, reducing the number of indicated procedures omitted by scene GEMS
      providers could reduce on-site HEMS times. For interfacility missions, further
      study is indicated to determine what occurs before HEMS is contacted and while
      HEMS is on-site.

PMID- 11331828
TI  - Functional outcome after open repair of abdominal aortic aneurysm.
AB  - INTRODUCTION: Detailed information on functional outcome after open abdominal
      aortic aneurysm (AAA) repair is sparse. Information about functional outcome of
      open AAA repair is essential to allow comparison of treatment modalities.
      METHODS: To determine the functional outcome of patients after open repair of
      AAA, we reviewed 154 consecutive, nonemergency open repairs of infrarenal AAAs
      between 1990 and 1997 and each patient's medical records. Clinical variables were
      recorded for each patient, as were multiple outcomes, including ambulatory
      status, independent living status, current medical condition, and the patient's
      perception of recovery and satisfaction. Eighty-seven patients or their families
      were available for current telephone interview to obtain information about
      objective functional activities, including walking and driving, and subjective
      functional information, including assessment of complete recovery and willingness
      to undergo AAA repair again. Chart data were available for all 154 patients.
      RESULTS: There were 42 women and 112 men. A total of 139 operations were
      elective, and 15 were urgent. The operative mortality rate was 4%, mean hospital
      stay was 10.7 +/- 1.3 days, and mean intensive care unit stay was 4.57 +/- 1.17
      days. Seventeen (11%) patients required transfer to a skilled nursing facility
      with a mean stay of 3.66 +/- 2.9 months. All patients were ambulatory
      preoperatively, whereas at last follow-up (median, 25 months; range, 0.13-108.5
      months), 100 (64%) of the patients remained ambulatory, 34 (22%) required
      assistance, and 12 (14%) were nonambulatory. At current assessment by telephone
      interview, 33% of patients described a decrease in their functional activity
      including driving, shopping, and traveling compared with their preoperative
      status, whereas 67% were unchanged. When asked to assess their own degree of
      recovery, 64% of patients stated that they experienced complete recovery with an
      average time to recovery of 3.9 months, whereas 33% said they had not fully
      recovered at a mean follow-up of 34 months. Sixteen (18%) patients said they
      would not undergo AAA repair again knowing the recovery process, even though they
      appeared to fully understand the implication of AAA rupture. CONCLUSION: Patients
      undergoing open AAA repair generally experienced significant freedom from
      surgical complications. However, substantial functional impairment was present.
      It is unclear whether the functional disability resulted from the AAA surgery or
      from aging and comorbidities unrelated to surgery.

PMID- 11331829
TI  - Outcome after unilateral hypogastric artery occlusion during endovascular
      aneurysm repair.
AB  - PURPOSE: The purpose of this study was to determine the long-term functional
      outcome after unilateral hypogastric artery occlusion during endovascular stent
      graft repair of aortoiliac aneurysms. METHODS: During a 41-month period, 157
      consecutive patients underwent elective endovascular stent graft repair of
      aortoiliac aneurysms with the Medtronic AneuRx device. Postoperative computed
      tomography scans were compared with preoperative scans to identify new
      hypogastric artery occlusions. Twenty-three (15%) patients had unilateral
      hypogastric occlusion, and there were no cases of bilateral occlusions. Telephone
      interviews about past and current levels of activity and symptoms were conducted,
      and pertinent medical records were reviewed. All 23 (100%) patients were
      available for the telephone interview. A disability score (DS) was quantitatively
      graded on a discrete scale ranging from 0 to 10 corresponding to "virtually bed
      bound" to "greater-than-a-mile" exercise tolerance. Worsening or improvement of
      symptoms was expressed as a difference in DS between two time points (-,
      worsening/+, improving). RESULTS: Among the 23 patients, two groups were
      identified: 10 patients (43%) had planned and 13 patients (57%) had unplanned or
      inadvertent occlusions. The patients in the two groups did not differ
      significantly in the mean age (73.4 vs 73.7 years), sex (male:female, 9:1 vs
      10:3), and duration of follow-up (15.6 vs 14.4 months). Nine (39%) of the 23
      patients, five patients in the planned and four patients in the unplanned group,
      reported significant symptoms of hip and buttock claudication ipsilateral to
      their occluded hypogastric arteries. The mean decrement from baseline of these
      nine patients in their DS postoperatively was -3.3. The symptoms were universally
      noted on postoperative day 1. Although most patients improved (89%), one (11%)
      never got better. Among those whose symptoms improved, the mean time to
      improvement was 15 weeks, but with a plateau thereafter resulting in a net
      decrement of DS of -2.3 from baseline. Finally, when questioned whether they
      would undergo the procedure again, all 23 patients unanimously answered, "Yes."
      CONCLUSIONS: A significant number (39%) of patients who sustain hypogastric
      artery occlusion after endovascular aneurysm repair have symptoms. Although most
      patients with symptoms have some improvement, none return to their baseline level
      of activity. Despite this, all patients in retrospect would again choose
      endovascular repair over conventional open repair.

PMID- 11331830
TI  - Endovascular exclusion of descending thoracic aortic aneurysms and chronic
      dissections: Initial clinical results with the AneuRx device.
AB  - OBJECTIVE: The objective of this study was to analyze a single-center experience
      in which descending thoracic aortic aneurysms (TAAs) were treated with a new self
      expanding endovascular prosthesis (Medtronic AVE). METHODS: Twenty-six patients
      (13 men, 13 women) with American Society of Anesthesiology grades II to IV and
      ages ranging from 53 to 92 years (average, 74 years) consented as part of a Phase
      I Food and Drug Administration-approved trial. Treated lesions included TAAs that
      were 5 to 10 cm in diameter, 12 diffuse dilations or fusiform aneurysms, and four
      saccular aneurysms. There were also nine chronic dissections (2 aneurysmal
      dilations and 7 symptomatic acute recurrent dissections). Three patients (2 with
      diffuse/fusiform and 1 with dissection) presented with hemothorax, contrast
      extravasation, or both. RESULTS: Twenty-five of the 26 patients who consented
      (96% technical success) were treated successfully with no surgical conversions.
      Eighteen patients have been followed up from 1 to 22 months (average, 9 months).
      One patient is lost to follow-up, and six patients have died (24%). One procedure
      related death (4%) occurred within the 30-day postoperative period and was caused
      by diffuse embolization. There were no device-related deaths. Five additional
      patients (20%) have died during the study of comorbid conditions. Complications
      included one massive myocardial infarction 24 hours after the procedure requiring
      balloon counterpulsation and long-term dialysis, one cardiac tamponade resulting
      from central line placement before the procedure, one progression of aneurysm
      dilation proximal to the device at 1 year, and one bilateral lower extremity
      paralysis occurring 12 hours after successful deployment. Seven patients (5
      women) had femoral artery reconstructions or iliac artery grafts to repair
      injuries during deployment catheter passage. Other significant parameters
      included average procedure time (2 hours 40 minutes; range, 1 hour 30 minutes to
      5 hours 30 minutes), 450 cc average blood loss (n = 25; 100-3000 cc) being
      replaced by means of autotransfusion with only two patients receiving banked
      blood products, and an average 2 days to resumption of normal diet, 1 day in the
      intensive care unit, and 5 days' hospitalization postprocedure in uncomplicated
      cases (n = 22). One patient had an endoleak immediately after the procedure that
      sealed without treatment. Follow-up of all patients ranging from 1 to 22 months
      (average, 9 months; n = 18) demonstrates continued exclusion of the aneurysm with
      no endoleaks and either stable or decreasing aneurysm volume, except in one
      patient with volume increase and no obvious etiology who continues to be
      investigated. CONCLUSIONS: The study suggests that endovascular prosthesis
      exclusion of TAAs with an AneuRx self-expanding tubular device may be effective
      in many patients who are at significant risk for open surgical repair and
      substantiates further clinical investigation to confirm these findings.

PMID- 11331831
TI  - Vascular complications in high-performance athletes.
AB  - PURPOSE: The purpose of this study was to evaluate our experience with the
      diagnosis and management of vascular injuries in a group of high-performance
      athletes. METHODS: Between June 1994 and June 2000, we treated 26 patients who
      sustained vascular complications as a result of athletic competition. Clinical
      presentation, type of athletic competition, location of injury, type of therapy,
      and degree of rehabilitation were analyzed retrospectively. RESULTS: The mean age
      of the patients was 23.8 years (range, 17-40). Twenty-one (81%) patients were
      men, and five (19%) were women. Athletes included 8 major-league baseball
      players, 7 football players, 2 world-class cyclists, 2 rock climbers, 2 wind
      surfers, 1 swimmer, 1 kayaker, 1 weight lifter, 1 marksman, and 1 volleyball
      player. There were 14 (54%) arterial and 12 (46%) venous complications. Arterial
      injuries included 7 (50%) axillary/subclavian artery or branch artery aneurysms
      with secondary embolization, 6 (43%) popliteal artery injuries, and 1 (7%) case
      of intimal hyperplasia and stenosis involving the external iliac artery.
      Subclavian vein thrombosis (SVT) accounted for all venous complications. Five of
      the seven patients with axillary/subclavian branch artery aneurysms required
      lytic therapy for distal emboli, and six required operative intervention. All
      popliteal artery injuries were treated by femoropopliteal bypass graft with
      autogenous saphenous vein. The external iliac artery lesion, which occurred in a
      cyclist, was repaired with limited resection and vein patch angioplasty. All 12
      patients with SVT were treated initially with lytic therapy and anticoagulation.
      Eight patients required thoracic outlet decompression and venolysis of the
      subclavian vein. Thirteen arterial reconstructions have remained patent at an
      average follow-up of 31.9 months (range, 2-74). One patient with a popliteal
      artery injury required reoperation at 2 months for occlusion of his bypass graft.
      Eleven of the patients with an arterial injury were able to return to their prior
      level of competition. All of the patients with SVT have remained stable without
      further venous thrombosis and have returned to their usual level of activity.
      CONCLUSIONS: Athletes are susceptible to a variety of vascular injuries that may
      not be easily recognized. A high level of suspicion, a thorough workup including
      noninvasive studies and arteriography/venography, and prompt treatment are
      important for a successful outcome.

PMID- 11331832
TI  - Iatrogenic vascular injuries from percutaneous vascular suturing devices.
AB  - OBJECTIVE: The purpose of this study was to examine the patterns of injury and
      the strategies of surgical repair of iatrogenic vascular injuries from a
      percutaneous vascular suturing device after arterial cannulation. METHODS: We
      retrospectively reviewed the clinical experience from an academic vascular
      surgical practice over a 2-year period. The subjects were patients undergoing
      vascular repair of iatrogenic vascular injury after deployment of a percutaneous
      vascular suturing device. Interventions were direct repair of arterial injury
      (with or without device extraction) or arterial thrombectomy and repair. The main
      outcome variables included patterns of arterial injury, magnitude of arterial
      repair, limb salvage, hospital stay, and perioperative mortality and morbidity
      rates. RESULTS: From August 1998 through August 2000, eight patients (4 men, 4
      women; median age, 55 years; range, 44-80 years) required vascular operations for
      complications of percutaneous suturing devices after diagnostic (2) or
      therapeutic (6) arteriograms through a transfemoral approach. Complications
      included four pseudoaneurysms (1 infected) due to arterial tear from suture pull
      through, two entrapped closure devices due to device malfunction, and two
      arterial thromboses due to narrowing/severe intimal dissection. All patients
      required operative intervention. Direct suture repair with or without device
      removal was performed in five patients, arterial debridement with vein patch
      angioplasty in one patient, and arterial thrombectomy and vein patch angioplasty
      in two patients. There were no perioperative deaths. The median hospital stay was
      5 days (range, 2-33). Limbs were salvaged in all patients with a mean follow-up
      of 4.8 months (range, 1-13). CONCLUSIONS: Although abbreviated postangiography
      recovery periods and early ambulation have motivated the widespread use of
      percutaneous suturing devices, the infrequent occurrence of vascular injuries
      produced by these devices can be significantly more challenging than simple acute
      pseudoaneurysms or hemorrhage. In addition, thrombotic complications have a small
      but finite risk of limb loss.

PMID- 11331833
TI  - Wound infections involving infrainguinal autogenous vein grafts: a current
      evaluation of factors determining successful graft preservation.
AB  - PURPOSE: The purpose of this study was to review the natural history and clinical
      outcome of patients with infrainguinal autogenous graft infection (IAGI), to
      evaluate the effectiveness of attempted graft preservation, to determine those
      variables associated with graft salvage, and to better determine optimal
      treatment. STUDY DESIGN: We retrospectively reviewed the records of patients
      undergoing infrageniculate vein grafts at three hospitals between 1994 and 2000
      who had a wound infection involving the graft. Clinical and bacteriologic
      variables were analyzed and correlated with graft salvage, limb salvage, and
      clinical outcome. RESULTS: During this 7-year period, 487 patients underwent an
      infrageniculate vein graft, and 68 (13%) had clinical evidence of IAGI. Twenty
      seven patients presented with drainage from the wound, 15 with wound separation
      and cellulitis, 18 with soft tissue infection extending to the graft, 4 with an
      abscess and cellulitis, and 4 with bleeding. Ten patients (15%) had systemic
      symptoms (defined as a white blood cell count > 15,000 and temperature > 38.5
      degrees C). Forty infections developed in the thigh, 17 in the groin, and 11 in
      the lower leg. An anastomosis was exposed in 15 patients. Wound cultures were
      positive for bacteria in 52 patients, and most infections were due to
      Staphylococcus aureus (18 patients) and S epidermidis (12 patients). Pseudomonas
      was cultured from seven infections. Twelve patients had polymicrobial infections.
      The interval from operation to infection ranged from 7 to 180 days. All patients
      were treated with oral antibiotics, 48 after intravenous antibiotics. Forty-five
      patients had operative debridement, including 18 who had muscle flap coverage.
      Four patients presented with hemorrhage, and three had immediate graft ligation
      and one graft excision. Follow-up ranged from 5 to 68 months (mean, 24.3 months),
      with 61 patients currently alive. Two patients died as a result of the IAGI
      (mortality rate, 2.9%). One had undergone a below-knee amputation, and one had a
      nonhealed wound but intact limb. Overall, 61 wounds (91%) healed, 4 patients
      required below-knee amputations, and 3 wounds did not heal. Fifty-eight grafts
      remained patent, 6 thrombosed, and 4 were ligated to control hemorrhage. Of the
      61 wounds that healed, the time required for healing ranged from 7 to 63 days. No
      patient with bleeding died because of the acute episode. No patient had delayed
      hemorrhage. All 18 patients treated with a muscle flap healed. Bleeding (P
      <.001), elevated white blood cell count (P <.029), fever (P <.001), and renal
      insufficiency (creatinine level > 1.5; P <.056) were the only variables
      statistically significant in predicting graft failure or limb loss. With the use
      of life-table analysis, graft patency was 94%, 72%, and 72% at 1, 3, and 5 years,
      and limb salvage was 97%, 92%, and 92% at the same intervals, respectively.
      CONCLUSIONS: Most patients with an IAGI can be successfully treated with graft
      and limb preservation. In contrast to earlier studies, an exposed anastomosis,
      interval to infection, or Pseudomonas infection is not associated with graft
      failure. Graft salvage is less likely in patinets with fever, leukocytosis, and
      renal insufficency, but because most grafts remained patent, graft preservation
      is recommended for these patients. Graft ligation or excision should be reserved
      for patients presenting with bleeding or sepsis.

PMID- 11331835
TI  - Carotid endarterectomy with normal findings from a completion study: Is there
      need for early duplex scan?
AB  - OBJECTIVE: The objective of this study was to determine the value of early (< 6
      months) duplex scanning after carotid endarterectomy (CEA) with an intraoperative
      completion study with normal results. Attention was paid to restenosis rates and
      reoperation for recurrent stenosis within the first 6 months. METHODS: A
      retrospective review was performed on 380 CEAs (338 patients) with intraoperative
      completion studies and duplex surveillance within the first 6 months. Results of
      completion studies, restenosis rates, and recurrent symptoms were evaluated for
      each operation. Studies were performed from 0 to 200 days postoperatively
      (median, 28). RESULTS: Intraoperative completion studies included 333 angiograms,
      26 duplex scans, and 21 angiograms with duplex scans. Of the 380 intraoperative
      completion studies, 28 (7.5%) had abnormal findings, including 14 abnormal
      internal carotid arteries (ICAs). Twenty-four procedures were revised, and the
      findings of all repeat completion studies were normal. Of the initial completion
      studies, in four cases, abnormalities (3 ICAs) were insignificant and did not
      warrant further intervention. Follow-up ICA duplex scans had normal results after
      364 (95.8%) CEAs. There were 14 mild recurrent ICA stenoses and two moderate
      recurrent ICA stenoses; neither had abnormal findings from the completion study.
      There were no severe recurrent ICA stenoses. External carotid artery (ECA)
      recurrent stenosis included 7 mild, 15 moderate, and 9 severe restenoses.
      CONCLUSIONS: Only 0.5% of CEAs developed moderate restenosis. No procedures had
      severe recurrent stenosis on duplex scan within the first 6 months, and none
      required intervention. Duplex surveillance in the first 6 months is relatively
      unproductive, providing that there were normal results from an intraoperative
      completion study for each patient. Routine surveillance can be started at 1 year.

PMID- 11331834
TI  - Intraoperative superficial femoral artery balloon angioplasty and popliteal to
      distal bypass graft: an option for combined open and endovascular treatment of
      diabetic gangrene.
AB  - PURPOSE: The purpose of this study was to evaluate the results of combining
      intraoperative balloon angioplasty (IBA) of the superficial femoral artery (SFA)
      with distal bypass graft originating from the popliteal artery as a method of
      lower extremity revascularization in diabetic patients with gangrene. METHODS:
      Among 380 infrainguinal bypass grafts performed over a 6-year period, there were
      110 reversed saphenous vein bypass grafts to the tibial or pedal arteries to
      treat diabetic patients with gangrene. Diffuse infrainguinal disease was treated
      with femoral-distal bypass graft (long; n = 46). Popliteal-distal bypass graft
      was performed when the inflow femoral artery was not significantly diseased
      (short; n = 52). Focal SFA stenosis and severe infrageniculate disease were
      treated with combined IBA of the SFA and distal bypass graft originating from the
      popliteal artery (combined; n = 12). Follow-up was performed with duplex scan
      surveillance of both the bypass graft and IBA sites. Treatment groups were
      compared with life-table analysis. RESULTS: There were no perioperative graft
      failures or amputations. The perioperative mortality rate was 1% (1 of 110). The
      2-year primary patency rates were similar in the three groups: 72% in the long
      bypass graft group, 82% in the short bypass graft group, and 76% in the combined
      group (P =.8, log-rank test). SFA IBA sites developed recurrent stenosis in two
      patients, at 7 and 48 months; both were detected with surveillance and treated
      with percutaneous transluminal balloon angioplasty. The overall 5-year rate of
      primary patency was 63%, secondary patency was 78%, limb salvage was 81%, and
      survival was 35%. There were no significant differences among the three treatment
      groups with respect to these outcomes. CONCLUSION: Results with the combined
      procedure were similar to those achieved with either femoral-distal bypass graft
      or popliteal-distal bypass graft without SFA IBA. These data suggest that IBA of
      the inflow SFA may be combined with popliteal to distal bypass graft and that
      this technique is a reasonable alternative to longer, femoral-origin bypass graft
      in selected diabetic patients with gangrene.

PMID- 11331836
TI  - Arteriovenous fistula construction in the thigh with transposed superficial
      femoral vein: our initial experience.
AB  - PURPOSE: The National Kidney Foundation-Dialysis Outcomes Quality Initiative
      guidelines favor autogenous vein for arteriovenous fistulas (AVFs). This report
      describes our experience constructing AVFs in the lower extremities of selected
      patients with the superficial femoral vein (SFV). PATIENTS AND METHODS: This is a
      retrospective analysis of 25 patients who had AVF construction with SFV from
      March 1998 to July 2000. In all patients upper extremity access had been
      exhausted. Eighteen (72%) patients were female, 15 (60%) had diabetes, and 14
      (56%) were obese (body mass index > 30 kg/m(2)). The SFV was freed from the
      supragenicular popliteal level to the profunda femoris vein and divided distally.
      Eighteen (72%) patients had SFV transposition and distal superficial femoral
      artery reimplantation; 10 veins were banded to reduce the incidence of
      postoperative steal syndrome. In seven patients (28%) a composite loop fistula
      was constructed with a deeply buried 4- to 7-mm polytetrafluoroethylene (PTFE)
      graft proximally and with superficially transposed SFV distally. One of these
      seven patients had a PTFE above-knee femoral-popliteal bypass graft with banding
      of the vein at its takeoff from the distal PTFE graft. RESULTS: Mean follow-up
      was 9.1 months. One patient died before the fistula could be used. Seven patients
      (28%) experienced major wound complications. Mean ankle/brachial index before
      operation was 1.03, and after operation it was 0.81 (paired difference [n = 16] =
      -0.26.) Mean ankle circumference before operation was 19.5 cm, and after
      operation it was 20.7 cm (paired difference [n = 17] = +0.87.) Cumulative primary
      fistula patency at 6 and 12 months was 78% and 73%, respectively. Cumulative
      secondary fistula patency at 6 and 12 months was 91% and 86%, respectively. There
      were no fistula infections. One patient eventually had an above-knee amputation
      after experiencing an acute compartment syndrome. Eight patients required a
      second operation to alleviate a symptomatic steal syndrome. CONCLUSIONS: The SFV
      is an excellent conduit for vascular access, whether it is transposed or is part
      of a composite PTFE-SFV fistula. In this series, fistula infection was
      nonexistent, thrombosis rates were low, and clinical evidence of venous
      hypertension was minimal. The major impediment to unrestricted use of SFV in
      constructing AVFs is a high incidence of clinically significant postoperative
      ischemia requiring reoperation.

PMID- 11331838
TI  - Nerve-preserving aortoiliac reconstruction surgery: anatomical study and surgical
      approach.
AB  - OBJECTIVE: Dysfunctional ejaculation and, to a lesser extent, dysfunctional
      erection caused by disruption of efferent sympathetic pathways is a common
      complication after aortoiliac reconstruction surgery. The aim was to give an
      anatomic motivation for a nerve-preserving approach on the basis of right-sided
      unilateral disruption of lumbar splanchnic nerves. METHODS: Anatomic and
      microscopic analysis of preaortic and para-aortic retroperitoneal regions in
      human cadavers was performed. Anatomic analysis was conducted of two aortoiliac
      reconstruction operations performed on human cadavers; one was performed
      according to a single-blind procedure, the second with a modified procedure.
      RESULTS: The lumbar splanchnic nerves supplying the superior hypogastric plexus
      from the right side were found to be less voluminous than the left-sided ones.
      The superior hypogastric plexus was found slightly shifted to the left of the
      midsagittal plane across the abdominal aorta and its bifurcation. Microscopic
      analysis revealed a thin fascia between the aorta and the subperitoneal tissue
      compartment. This fascia was used as a plain of dissection to mobilize the
      preaortic nerve-plexuses without damage from the aortic wall. Analysis of the
      specimens operated on showed a significant difference in nerve disruption. The
      standard procedure caused total disruption of the superior hypogastric plexus and
      extensive disruption of the inferior mesenteric plexus. The modified procedure
      only caused right-sided unilateral disruption of lumbar splanchnic nerves.
      CONCLUSION: The autonomic nerves supplying the bladder neck, the vas deferens,
      and the prostate are closely related to the abdominal aorta and its bifurcation.
      Right-sided unilateral disruption of lumbar splanchnic nerves without further
      damage to nervous structures would ensure at least one functional sympathetic
      pathway remaining after aortoiliac reconstruction surgery.

PMID- 11331837
TI  - Relationship between antiphospholipid antibodies and progression of lower
      extremity arterial occlusive disease after lower extremity bypass operations.
AB  - PURPOSE: Antiphospholipid antibodies (APLs), which consist of anticardiolipin
      antibodies (ACLs) or lupus anticoagulant (LA), are associated with venous
      thrombosis, stroke, and cardiac events. Although they are present in many
      patients with lower extremity atherosclerotic occlusive disease (LEAOD), the
      relationship between APL and the progression of LEAOD has not been reported. A
      comparison of progression of LEAOD as determined with direct imaging studies in
      patients with and without APL forms the basis for this report. METHODS: APL+
      patients (immunoglobulin M [IgM] or IgA or IgG ACL > 3 SD units above control
      mean or positive LA) who underwent lower extremity bypass grafting between
      January 1990 and June 1999 (n = 79) were compared with an APL control group (n =
      68). Members of the study and control groups were similar with respect to age,
      procedure, sex, length of follow-up, and multiple atherosclerosis risk factors.
      Progression of LEAOD was determined by comparing preoperative arteriograms with
      postoperative imaging studies (arteriograms or duplex scanning). External iliac,
      common femoral, superficial femoral and popliteal arteries were graded as < 50%
      stenosis, > or = 50% stenosis, or occluded. Posterior tibial and anterior tibial
      arteries were graded as patent or occluded. Progression was defined as any
      increase in stenosis category. RESULTS: The mean follow-up period was 31 months
      for APL+ and 35 months for APL- patients (P = not significant). Progression of
      LEAOD occurred in 58 (73%) of 79 APL+ patients and in 25 (37%) of 68 APL-
      patients (P <.001). There was no difference in progression in external iliac or
      common femoral arteries. Differences in progression were noted in more distal
      arteries; APL+ patients had significantly more progression in superficial femoral
      (45% vs 16%, P <.01), popliteal (31% vs 12%, P <.01), posterior tibial (29% vs
      13%, P <.05), and anterior tibial arteries (29% vs 14%, P <.05). Multivariate
      logistic regression analysis showed a significant independent association between
      the presence of APL and progression of LEAOD (P <.0001). CONCLUSION: In this
      study, the presence of APL in patients undergoing lower extremity bypass
      operations was a significant independent risk factor for progression of LEAOD. We
      conclude that this patient group should be closely monitored in the postoperative
      period and appears ideally suited for prospective studies of therapies to modify
      LEAOD progression.

PMID- 11331839
TI  - Common femoral artery ligation and local debridement: a safe treatment for
      infected femoral artery pseudoaneurysms.
AB  - PURPOSE: The management of infected femoral artery pseudoaneurysms (IFAPs) is
      difficult and controversial. Use of synthetic or autologous conduit during
      arterial revascularization in these cases is complicated by the presence of
      sepsis and unavailability of autologous venous conduit. We present the results of
      common femoral artery (CFA) ligation and local drainage with debridement for the
      treatment of IFAP. METHODS: A retrospective chart review of six consecutive
      patients from 1995 to 1999 who presented with IFAP from intravenous drug abuse
      was performed. Inpatient records, anesthesia records, and outpatient clinic
      charts were reviewed. All patients were men with right-sided lesions. All six
      patients abused heroin, and five (83%) abused heroin and cocaine. All six
      patients had a duplex ultrasound scan, and five (83%) patients had a digital
      subtraction angiogram to confirm the clinical diagnosis. Proximal vascular
      control was achieved retroperitoneally through an oblique suprainguinal incision.
      After vascular isolation and test clamping of the distal external iliac artery
      (EIA), the pedal pulses were examined with continuous wave Doppler scan. If a
      Doppler signal was present, this was followed with CFA ligation and local
      drainage and debridement of the IFAP. RESULTS: Pain at injection site and fever
      with chills were present in five (83%) and three (50%) patients, respectively. A
      pulsatile groin mass and thigh or leg edema were present in five (83%) patients.
      Three patients (50%) had a palpable pedal pulse, and all six had a Doppler signal
      over a pedal artery at presentation. The mean white cell count was 15.6 thousand
      per cubic millimeter (range, 9.2-19.3). All patients had a Doppler signal over a
      pedal artery after distal EIA/CFA test occlusion and ligation. None of the
      patients required an amputation, and all six patients regained their preoperative
      ambulatory status. The mean follow-up period was 25 months. Two patients had mild
      claudication (5-6 blocks) at 18 months and 2 years after surgery. All six
      patients received drug rehabilitation, but they admitted to drug abuse after
      surgery and rehabilitation. CONCLUSION: CFA ligation and local debridement are
      safe treatment modalities for IFAP, if there is an intraoperative Doppler signal
      over a pedal artery during test occlusion of the distal EIA/CFA. CFA ligation
      avoids the use and therefore the risk of synthetic conduit infection, because
      there is a high incidence of postoperative drug injection despite aggressive drug
      rehabilitation.

PMID- 11331840
TI  - Randomized trial of vein versus Dacron patching during carotid endarterectomy:
      influence of patch type on postoperative embolization.
AB  - PURPOSE: A recent overview indicated that although routine patching is safer than
      routine primary closure after carotid endarterectomy (CEA), there is no
      systematic evidence that patch type influences outcome. However, most surgeons
      still believe that prosthetic patches are probably more thrombogenic than vein
      patches. This study tested the hypothesis that there was no difference in
      thrombogenicity between the different patch types. METHODS: A total of 274
      patients undergoing 276 CEAs were randomized to either Dacron-patch closure (n =
      137) or vein-patch closure (n = 139). All patients with an accessible cranial
      window were monitored for 3 hours postoperatively with transcranial Doppler
      scanning (TCD). The number of emboli and rate of embolization were quantified
      with the requirement for selective dextran therapy to control high rates of
      postoperative embolization. All patients were assessed postoperatively and again
      at 30 days by a neurologist, and all patients underwent a duplex examination at
      30 days. RESULTS: The 30-day death/any stroke rate was 2.2% for patients in the
      Dacron-patch group and 3.6% for patients in the vein-patch group (P =.72).
      Patients in the Dacron-patch group had a higher incidence of postoperative emboli
      (median, 5; interquartile range, 0-10.5) than patients in the vein-patch group
      (median, 3; interquartile range, 1-17; P =.028). However, the incidence of
      detecting more than 50 emboli was virtually identical, and patch type had no
      effect on the incidence of high-rate, sustained embolization that required
      dextran therapy (5.3% for Dacron, 3.7% for vein). No patient had a carotid
      thrombosis at 30 days. CONCLUSION: Sustained, high-rate embolization, previously
      shown to be highly predictive of progression to carotid thrombosis, appears to be
      patient dependent, rather than related to patch type.

PMID- 11331841
TI  - Technical aspects and current results of carotid stenting.
AB  - PURPOSE: We reviewed our experience with carotid stenting (CS), focusing on
      technical evolution and results. METHODS: From September 1995 to February 2000,
      77 patients with 83 internal (n = 68) and common carotid artery lesions (n = 15)
      were selected for CS. This patient population was categorized into three
      consecutive periods based on patient selection, material, and technical skills.
      For internal carotid artery lesions, period I included 11 patients treated by
      means of direct carotid puncture with balloon expandable stents; period II
      included 42 patients treated by means of a femoral approach with self-expandable
      stents; and period III included 15 patients in whom monorail system and cerebral
      protection devices were used. Common carotid artery lesions were treated by means
      of carotid puncture in five patients and by means of a femoral approach in 10
      patients. In only two of the latter cases, cerebral protection devices were used.
      RESULTS: The overall immediate success rate, defined as successfully treated
      stenosis with no neurological events, was 89.7% for internal carotid artery
      lesions and 100% for common carotid artery lesions. All neurological events,
      which consisted of reversible events (4.4%), minor stroke (1.5%), and major
      stroke (2.9%), occurred during periods I and II. In periods I, II, and III, the
      rate of surgical conversion was 18%, 9.5%, and 0%, respectively, the rate of
      transient ischemic attack and reversible ischemic neurologic deficit was 0%, 7%,
      and 0%, respectively, and the rate of minor and major stroke was 0%, 7%, and 0%,
      respectively. All major strokes were cleared with intra-arterial thrombolysis. At
      discharge, the success rates defined by means of the absence of conversion and
      neurological events were 82% during period I, 76% during period II, and 100%
      during period III. The freedom from neurological deficits rates were 100%, 97.6%,
      and 100%, respectively. During follow-up, six significant asymptomatic restenoses
      were detected with duplex scanning; however, only one patient required
      reintervention. CONCLUSION: Technical skills and technological improvement,
      including low-profile balloon and catheter, cerebral protection device, and intra
      arterial rescue techniques, may reduce the rate of neurological events associated
      with CS. Technical improvements should be given careful consideration before the
      initiation of randomized trials comparing CS and carotid endarterectomy.

PMID- 11331842
TI  - Poor durability of carotid angioplasty and stenting for treatment of recurrent
      artery stenosis after carotid endarterectomy: an institutional experience.
AB  - PURPOSE: Recurrent stenosis after carotid endarterectomy (CEA) is often regarded
      as an optimal application of carotid artery angioplasty and stenting (CAS). The
      extended durability of CAS for recurrent carotid artery stenosis after CEA is
      unknown. We present the intermediate-term surveillance results for all eight CAS
      procedures performed over a 28-month period at a single tertiary referral center.
      METHODS: Patients had recurrent carotid stenosis after CEA, whether symptomatic
      or asymptomatic, of 80% to 99% stenosis on preprocedural carotid duplex scan
      examination. Uncovered, self-expanding metal stents, in conjunction with
      angioplasty, were used in all patients. Baseline and scheduled interval follow-up
      duplex ultrasound scan was used to assess intrastent restenosis. Further
      angiography was reserved for those patients obtaining additional intervention.
      RESULTS: One transient ischemic attack was observed 1 day after the procedure,
      and no cerebral infarcts occurred. All patients had angiographic resolution of
      the stenosis and postprocedural duplex scan studies without residual stenosis.
      Subsequent interval surveillance duplex scan examinations revealed significant
      (60%-79%) to critical (80%-99%) recurrent stenosis in six (75%) of eight
      patients, two of whom went on to further interventions. Of those with intrastent
      restenosis, four (75%) progressed to critical (80%-99%) stenosis. Mean follow-up
      was 20.2 months (range, 12-37 months). The two lesions that have not yet shown
      restenosis are those with the shortest follow-up interval, each at 12 months.
      CONCLUSIONS: In contrast to the optimistic claims in other series, this limited
      series suggests that angioplasty with stenting for recurrent carotid artery
      occlusive disease after CEA, although relatively safe in the short term, has
      significant limitations in terms of durability of results.

PMID- 11331843
TI  - Longitudinal ruptures of polyester knitted vascular prostheses.
AB  - AIM: The purpose of the study was the characterization of a type of rupture
      occurring on warp-knitted polyester vascular prostheses. MATERIALS AND METHODS:
      We studied 20 cases of warp-knitted polyester vascular prostheses that were
      explanted from humans that showed a longitudinal rupture as a part of a
      collaborative retrieval program. All the prostheses were immediately fixed in a
      10% formaldehyde solution after their explantation in the operating room. The
      clinical data of these cases were recorded. The explants were photographed,
      washed to eliminate the surrounding tissues, and photographed again. The ruptures
      were characterized with macroscopic examination, optical stereomicroscopy, and
      scanning electron microscopy. RESULTS: The mean duration of implantation of the
      prostheses was 16.0 +/- 3.3 years (range, 9-20.7 years). The prostheses were
      Cooley Double Velour (n = 15) and Microvel Double Velour (n = 5). There were 16
      aortobifemoral bypass grafts, 1 aorto-biiliac, 1 aorto-aortic, 1 iliofemoral, and
      1 axillobifemoral. The longitudinal ruptures occurred on two specific parts of
      the prostheses: the guide line (6 cases) and the remeshing line (11 cases). In
      three cases both lines were affected. Scanning electron microscopy showed major
      degradation of the trilobar filaments of the velour and gradual ruptures of the
      flat filaments of the remeshing and guide lines. CONCLUSIONS: In this study, we
      have identified a specific mechanism of late (9-20 years) longitudinal rupture of
      knitted polyester prostheses consisting of degradation of the polyester filaments
      along the remeshing and guide lines that run the length of the graft.

PMID- 11331845
TI  - Endoscopic versus open subfascial division of incompetent perforating veins in
      the treatment of venous leg ulceration: long-term follow-up.
AB  - PURPOSE: Subfascial division of incompetent perforating veins seems to be a
      successful treatment for patients with venous leg ulceration (CEAP 6). For
      postoperative wound complications, endoscopic techniques are more common than
      open subfascial division of incompetent perforating veins (Linton procedure). We
      investigated the long-term results of ulcer healing and recurrence rates and
      compared them with preoperative and postoperative duplex findings. METHODS:
      Patients with venous ulceration on the medial side of the lower leg were randomly
      allocated to endoscopic exploration or open exploration by means of the modified
      Linton approach. Ulcer healing and recurrence rates were documented. RESULTS:
      Thirty-nine patients were randomly allocated to exploration, 19 patients to open
      subfascial division of incompetent perforating veins (Linton group), and 20
      patients to subfascial endoscopic division of incompetent perforating veins (SEPS
      group). During the follow-up period, four patients in the SEPS group died, all of
      causes other than the venous leg ulcer. Because of a squamous cell carcinoma that
      had developed in the venous ulcer, one patient in the SEPS group underwent a
      below-knee amputation. In a mean follow-up period of 50.6 months, the venous
      ulceration of all 18 patients in the Linton group who were available for follow
      up initially healed. The recurrence rate in this group was 22% (4 patients). In
      the SEPS group, the mean follow-up period for 19 patients was 46.1 months, with
      the ulceration healing in 17 patients and a recurrence rate of 12% (2 patients).
      The presence of deep venous incompetence (DVI) did not influence the recurrence
      rates (P =.044, Fisher exact test), but it significantly influenced the
      development of new incompetent perforating veins (3 of 10 without DVI; 7 of 10
      with DVI; P =.011, binomial test). CONCLUSION: The long-term follow-up results of
      the endoscopic division of perforating veins are comparable with those of the
      open division of perforating veins (modified Linton procedure).

PMID- 11331844
TI  - Trends in the incidence of venous stasis syndrome and venous ulcer: a 25-year
      population-based study.
AB  - BACKGROUND: The incidence rates of venous stasis syndrome and venous ulcer are
      uncertain, and trends in incidence are unknown. METHODS: We performed a
      retrospective review of the complete (inpatient and outpatient) medical records
      of a community population (Olmsted County, Minnesota) to estimate the incidence
      of venous stasis syndrome and venous ulcer during the 25-year period, 1966 to
      1990, and to describe trends in incidence. RESULTS: A total of 1131 patients
      received a first lifetime diagnosis of venous stasis syndrome. A total of 263
      patients received a first lifetime diagnosis of venous ulcer. The overall
      incidence of venous stasis syndrome and venous ulcer were 76.1 and 18.0 per
      100,000 person-years, respectively. The incidence of both was higher in women
      than in men (83.7 vs 67.4 per 100,000 person-years for venous stasis syndrome;
      20.4 vs 14.6 per 100,000 for venous ulcer) and increased with age for both sexes.
      There was no clear trend in the incidence of venous stasis syndrome over the 25
      year period. Compared with 1966 to 1970, the incidence of venous ulcer decreased
      in 1971 to 1980, but was unchanged after 1981. Among 945 patients with venous
      stasis only, 60 subsequently had a venous ulcer. The average (+/- SD) time from
      venous stasis diagnosis to development of a venous ulcer was 5.0 (+/- 5.0) years.
      CONCLUSION: Venous stasis syndrome and venous ulcer are common, especially in the
      elderly population. The incidence of venous stasis syndrome has not changed since
      1966, and venous ulcer incidence is unchanged since 1981. More accurate
      identification of patients at risk for venous stasis syndrome and venous ulcer
      and more effective prevention are needed.

PMID- 11331846
TI  - Interobserver and intraobserver reproducibility of peripheral blood and oxygen
      pressure measurements in the assessment of lower extremity arterial disease.
AB  - INTRODUCTION: Peripheral blood pressure measurements play a prominent role in the
      diagnosis and follow-up of patients with peripheral vascular diseases. Toe
      pressure of the hallux (TP1) and second toe (TP2) and transcutaneous oxygen
      pressure (TCPO2) measurements are becoming more important. The ankle/brachial
      pressure index (ABPI) is known to be a reliable parameter, but the toe pressure
      and TCPO2 are evaluated less thoroughly. Therefore, we evaluated the
      reproducibility of TP1, TP2, TCPO2, ABPI, ankle pressure (AP), and brachial
      pressure (BP). PATIENTS AND METHODS: In 54 patients with various stages of
      peripheral vascular disease, the intraobserver and interobserver reproducibility
      of BP, AP, ABPI, TP1, TP2, and TCPO2 was investigated by calculating the
      repeatability coefficient (RC) and the intraclass correlation coefficient (ICC)
      and by using Bland-Altman plots. RESULTS: The intraobserver and interobserver
      reproducibility at 1 day and after 1 week of BP, AP, ABPI, and TP1 was
      substantial and comparable (ICC range, 0.80-0.99), except for the BP after 1
      week. The TP2 and TCPO2 were less reproducible (ICC range, 0.62-0.98). The
      interobserver RC of BP was 31 mm Hg; of AP, 44 mm Hg; of ABPI, 27%; of TP1, 41 mm
      Hg; of TP2, 67 mm Hg; and of TCPO2; 30 mm Hg. The difference plot showed that the
      observer variability was equally distributed across the range of pressure in all
      measurements. CONCLUSION: The BP, AP, ABPI, and TP1 have a substantial
      intraobserver and interobserver reproducibility, whereas TP2 and TCPO2 show worse
      reproducibility. Especially when low values (or values around a cutoff value) are
      measured, the RC should be taken into account, and repetition of the measurement
      is advocated.

PMID- 11331847
TI  - Endovascular revascularization of renal artery stenosis: technical and clinical
      results.
AB  - PURPOSE: The natural history of renal artery stenosis is progression with
      subsequent deterioration of kidney function and development of renovascular
      hypertension. Percutaneous transluminal renal angioplasty is effective in the
      treatment of nonostial lesions but less effective for ostial stenoses. Because of
      the poor technical success experienced with percutaneous transluminal renal
      angioplasty, stenting of ostial stenoses is becoming the standard of endovascular
      care. In this retrospective study we analyzed the technical and clinical outcomes
      after renal artery stenting in 73 consecutive patients. PATIENTS AND METHODS:
      From July 1992 to January 1999, 88 Palmaz stents were deployed in 85 renal artery
      stenoses in 73 patients, with a mean age of 67.9 +/- 9.4 years. Twelve patients
      (16%) underwent bilateral stent placement. Atheromatous lesions were the most
      prevalent (99%: 82% ostial, 16% nonostial). Most stents were implanted for
      suboptimal balloon dilation (52%) or dissection (24%). Mean percent stenosis was
      86% +/- 12%. Renal insufficiency (creatinine level > or = 1.5 mg/dL) was present
      in 50 (68%) patients, and uncontrolled hypertension (systolic > or = 160 mm Hg or
      diastolic > or = 90 mm Hg with more than two medications) was present in 57
      (78%). RESULTS: Primary technical success was achieved in 89%. At the initial
      procedure, three additional stents were placed for residual stenoses, and
      urokinase was used to treat one intraprocedural stent thrombosis, resulting in an
      assisted primary technical success rate of 94%. Major complications occurred in
      9.1% of stents placed: access artery thrombosis (n = 4), renal artery
      extravasation (n = 1), renal artery thrombosis (n = 1), and hematoma requiring
      operation (n = 2). Long-term clinical data were available on 69 (95%) patients at
      20 +/- 17 months. Overall, a significant decrease in systolic and diastolic
      pressures (P <.001) and reduction of medication (P <.01) were noted without a
      change in renal function (P = NS). Angiography was performed on 22 patients at
      11.3 +/- 10.3 months for persistent or worsening renal function or hypertension
      or for other reasons; 10 patients had significant restenoses in 14 renal
      arteries. CONCLUSION: Our retrospective analysis demonstrates that endovascular
      stenting of renal artery stenosis in patients with poorly controlled hypertension
      or deteriorating renal function is a safe and effective alternative treatment to
      surgical management.

PMID- 11331848
TI  - Common femoral vein dimensions and hemodynamics including Valsalva response as a
      function of sex, age, and ethnicity in a population study.
AB  - PURPOSE: In this study we assessed the normal common femoral vein (CFV)
      dimensions and related hemodynamics in a cohort assembled to permit contrasts by
      means of sex, age, and ethnicity. METHODS: The CFV diameter and the flow velocity
      were analyzed by means of duplex ultrasonography at rest and with a standardized
      Valsalva maneuver, with the subject in a 15% reverse Trendelenberg position. Mean
      levels of each of the CFV measurements were analyzed with age category, sex, and
      ethnicity, each adjusted for the other two. Multiple linear regression was used
      as a means of assessing the independent associations of age, sex, ethnicity, body
      mass index (BMI), and height to the CFV measurements. RESULTS: The average CFV
      diameter at rest was 11.84 mm, increasing to 14.27 mm during the Valsalva
      maneuver. There was a significant (P <.0001) decline in both diameter measures
      beginning in patients 60 years old. The CFV diameter was larger in men (12.90 mm)
      than in women (11.22 mm; P <.0001). The average CFV diameter in Hispanics,
      Africian Americans, and Asians was significantly smaller (P <.001) than in the
      non-Hispanic whites in multivarate analysis. The independence of these
      associations was confirmed by means of multivariate analysis, and positive
      associations of CFV diameter with height and BMI were documented. The Valsalva
      response was higher in men than in women (2.67 mm vs 2.29 mm), but the percentage
      change was similar. CFV velocity at rest decreased significantly (P <.0001) in
      patients older than 50 years. The mean CFV velocity was 13.87 cm/s, and the
      values were significantly (P <.0001) higher in women (14.58 cm/s) than in men
      (12.67 cm/s). In multivariate analysis CFV velocity was higher in African
      Americans than in the other ethnic groups. We also documented an independent
      inverse association of CFV with BMI. The CFV velocity response (peak expiration
      post-Valsalva) increased significantly at all ages, from 52% to 83%. The
      percentage increase in women (68%) was slightly higher than that in men (58%).
      African American subjects had a somewhat higher percentage increase (74%) than
      the other three ethnic groups (63% to 64%). Because the flow rate is determined
      more by the diameter than the velocity, CFV flow associations were similar to
      those for diameter. Because an older age predicted both decreased diameter and
      velocity, the flow reduction with age was pronounced. CONCLUSION: Quantitative
      normative data that are age-, sex-, and ethnic group-specific are reported on CFV
      diameter, velocity, and total flow rate, both at rest and with the Valsalva
      maneuver. CFV diameter, velocity, and flow rate varied significantly as a
      function of age, sex, ethnicity, height, and BMI. The data also provide a
      baseline assessment for subsequent evaluations of changes with time in this
      cohort.

PMID- 11331849
TI  - Suppression of experimental abdominal aortic aneurysms in the rat by treatment
      with angiotensin-converting enzyme inhibitors.
AB  - PURPOSE: Pathologic remodeling of the extracellular matrix is a critical
      mechanism in the development and progression of abdominal aortic aneurysms
      (AAAs). Although angiotensin-converting enzyme (ACE) inhibitors are known to
      alter vascular wall remodeling in other conditions, their effects on AAAs are
      unknown. In this study we assessed the effect of ACE inhibitors in a rodent model
      of aneurysm development. METHODS: Male Wistar rats underwent transient aortic
      perfusion with porcine pancreatic elastase, followed by treatment with one of
      three ACE inhibitors (captopril [CP], lisinopril [LP], or enalapril [EP]), an
      angiotensin (AT)1 receptor antagonist (losartan [LOS]), or water alone (9 rats in
      each group). Blood pressure and aortic diameter (AD) were measured before
      elastase perfusion and on day 14, with an AAA defined as an increase in AD
      (DeltaAD) of more than 100%. The structural features of the aortic wall were
      examined by means of light microscopy. RESULTS: Aneurysmal dilatation
      consistently developed within 14 days of elastase perfusion in untreated rats,
      coinciding with the development of a transmural inflammatory response and
      destruction of the elastic media (mean DeltaAD, 223% +/- 28%). All three ACE
      inhibitors prevented AAA development (mean DeltaAD: CP, 67% +/- 4%; LP, 18% +/-
      12%; and EP, 14% +/- 3%; each P <.05 vs controls). ACE inhibitors also attenuated
      the degradation of medial elastin without diminishing the inflammatory response.
      Surprisingly, the aneurysm-suppressing effects of ACE inhibitors were dissociated
      from their effects on systemic hemodynamics, and LOS had no significant effect on
      aneurysm development compared with untreated controls (mean DeltaAD, 186% +/-
      19%). CONCLUSION: Treatment with ACE inhibitors suppresses the development of
      elastase-induced AAAs in the rat. Although this is associated with the
      preservation of medial elastin, the mechanisms underlying these effects appear to
      be distinct from hemodynamic alterations alone or events mediated solely by AT1
      receptors. Further studies are needed to elucidate how ACE inhibitors influence
      aortic wall matrix remodeling during aneurysmal degeneration.

PMID- 11331850
TI  - Increased expression of HDJ-2 (hsp40) in carotid artery atherosclerosis: a novel
      heat shock protein associated with luminal stenosis and plaque ulceration.
AB  - PURPOSE: Evidence suggests that both humoral and cellular autoimmune processes
      directed toward heat shock proteins (hsp) contribute to the pathogenesis of
      atherosclerosis. We characterized a human hsp distinct from those previously
      characterized in atherosclerotic lesions, termed HDJ-2. METHODS: To determine the
      role of HDJ-2 in atherosclerosis, we compared the level of HDJ-2 mRNA expression
      with the level of hsp60 and hsp70 mRNA expression in 26 carotid endarterectomy
      specimens and 17 normal arteries. The level of expression of HDJ-2 mRNA was also
      correlated to the presence of plaque ulceration and the degree of luminal
      stenosis associated with the lesion. RESULTS: The expression of HDJ-2 and hsp70
      was significantly higher in carotid artery plaques as compared with normal
      arteries: HDJ-2, 6.7 +/- 1.6 vs 0.1 +/- 0.04, (P =.001); hsp70, 9.5 +/- 0.9 vs
      3.7 +/- 0.8, (P =.002). There was no significant difference in hsp60 expression
      between carotid artery plaques and normal arteries (21.0 +/- 0.9 vs 20.6 +/- 0.8,
      P =.65). Increased HDJ-2 expression in carotid artery plaques was independent of
      hsp70 (Pearson correlation, r = 0.11; Bartlett chi(2) analysis, P =.71). Within
      the ulcerated plaque group, there was a correlation between degree of stenosis
      and high HDJ-2 mRNA expression (r = 0.896, P =.016). However, there was no
      correlation between degree of stenosis and high HDJ-2 mRNA expression within the
      nonulcerated plaque group (r = 0.530, P =.076) or within the entire group of
      patients (r = 0.0085, P =.97). CONCLUSION: These results demonstrate that
      expression of HDJ-2 is significantly increased in atherosclerotic carotid artery
      plaques as compared with hsp60 and hsp70 and correlates with luminal stenosis in
      ulcerated atherosclerotic carotid artery plaques.

PMID- 11331851
TI  - Active site-inactivated factor VIIa prevents thrombosis without increased
      surgical bleeding: topical and intravenous administration in a rat model of deep
      arterial injury.
AB  - PURPOSE: The primary event in the procoagulant response after vascular
      interventions is the tissue factor (TF)-factor VIIa complex formation, which
      occurs when TF is exposed to the circulating blood by the inflicted trauma. Human
      recombinant active site-inhibited coagulation factor VIIa (FFR-rFVIIa) binds well
      to TF but cannot initiate blood coagulation, and should thereby block thrombus
      formation. This hypothesis was tested with a rat model of arterial thrombosis.
      METHODS: In a blinded randomized study, the antithrombotic and antihemostatic
      effects of FFR-rFVIIa and heparin were evaluated in a rat model of mechanical
      deep arterial injury. In one arm of the study, FFR-rFVIIa (0.2 mg in 150 microL)
      or vehicle alone was applied topically at the site of vascular injury. In the
      other arm, FFR-rFVIIa (4 mg/kg), heparin (1 mg/kg), or vehicle alone was injected
      intravenously. RESULTS: FFR-rFVIIa produced a powerful antithrombotic effect
      after both topical and intravenous administrations (P =.02 and P =.005,
      respectively) without increasing the surgical bleeding. Heparin prevented
      thrombosis equally well as FFR-rFVIIa (P =.0007), but doubled the surgical
      bleeding compared with FFR-rFVIIa (P =.03) and controls (P =.008). In the topical
      study, the antithrombotic effect was achieved without altering parameters of
      plasma anticoagulation (prothrombin time and activated partial thromboplastin
      time) or producing detectable levels of FFR-rFVIIa in plasma. CONCLUSION: In this
      model FFR-rFVIIa effectively inhibits thrombus formation without the expense of
      increased surgical bleeding, which indicates the potential of FFR-rFVIIa as an
      effective and safe strategy for prevention of thrombosis in reconstructive
      vascular surgery and various forms of percutaneous revascularization.

PMID- 11331852
TI  - Expression of molecular mediators of apoptosis and their role in the pathogenesis
      of lower-extremity varicose veins.
AB  - PURPOSE: In an earlier study, we observed a significant decrease in apoptosis in
      varicose veins, as compared with healthy veins, indicating that deregulated
      apoptosis plays a role in the pathogenesis of varicosities. In addition,
      significant differences were noted in the expression and subcellular localization
      of the cell cycle regulatory protein, cyclin D1 in varix tissues, as compared
      with controls. Because cell cycle checkpoint controls are linked to the signaling
      and execution of apoptotic cascades, we examined the expression of bcl-2 family
      members bax and bcl-x, known molecular mediators of apoptosis, and that of poly
      (ADP-ribose) polymerase (PARP), a downstream substrate of DNA cleavage. METHODS:
      Twenty varicose vein specimens were retrieved from 20 patients (10 men, 10 women;
      mean age, 53.6 +/- 4.7 years) undergoing lower-extremity varicose vein excision.
      Healthy greater saphenous vein segments (n = 27) were obtained from 27 patients
      (14 men, 13 women; mean age, 59.5 +/- 2.4 years) undergoing infrainguinal
      arterial bypass grafting surgery. All tissues were distal portions. As per CEAP
      classification for chronic lower-extremity venous disease, most of the patients
      were in class 2 for clinical signs (n = 11); some patients were in class 3 (n =
      4) or class 4 (n = 4), and only one patient was in class 5. Five 5-microm thick
      sections from formalin-fixed, paraffin-embedded specimens were used as a means of
      immunohistochemically localizing the expression of bax, bcl-x, and PARP, and 10
      random high-power fields per section were evaluated by two independent reviewers
      blinded to the clinical findings. Statistical analyses were conducted by means of
      chi(2), analysis of variance, Student and Fisher exact t tests with StatView
      software. RESULTS: Immunoreactivity to pro-apoptotic bax was significantly higher
      in the normal veins (P <.001). Cytoplasmic expression of bcl-x was prominent in
      the cells of the vasa vasorum in both varicose and healthy veins. PARP expression
      was diminished in the varicose vein group, with 2.8 +/- 0.7 (P =.01) and 1.4 +/-
      0.5 (P =.05) cells per high-power field in the intima and media, respectively.
      Neither bax nor PARP was noted in the adventitia of varicose veins, although
      their expression was detected in this layer of the control group (P <.001).
      CONCLUSION: The entry of smooth muscle cells into the apoptotic pathway may be
      regulated by the induction of bax in this model, because there is significant
      presence of this pro-apoptotic protein in healthy veins. Both bax and PARP are
      downregulated in varicose veins, as compared with healthy veins, and this may
      play a significant role in the pathogenesis of varicose veins.

PMID- 11331853
TI  - Successful endovascular repair of juxtarenal and suprarenal aortic aneurysms with
      a branched stent graft.
AB  - This case report describes a new technique for repairing pararenal aortic
      aneurysms with a transluminally placed triple-branched stent graft with sidearms
      extending into the superior mesenteric artery and renal arteries. Endovascular
      repair with the branched stent graft was attempted in two patients with a
      pararenal aortic Aneurysm. Stent grafting was technically successful in both
      patients. Although postoperative transient renal function impairment and
      paralytic ileus occurred in patient 2, these complications were gradually
      resolved in the perioperative period. A substantial shrinkage of the aneurysm was
      revealed by means of computed tomographic measurements in patient 1. In both
      patients, complete exclusion of the aneurysm and patency of the bilateral renal
      arteries and the superior mesenteric artery were confirmed by means of follow-up
      computed tomographic images at 2 years. This minimally invasive approach for
      pararenal aortic aneurysms appears to be a viable therapeutic option for patients
      who are at high risk for open surgery.

PMID- 11331854
TI  - Femoral artery thrombosis after percutaneous thrombin injection of an external
      iliac artery pseudoaneurysm.
AB  - Ultrasound-guided percutaneous thrombin injection has been developed as a less
      invasive and highly successful treatment of iatrogenic femoral pseudoaneurysms.
      Most of these lesions have been the result of catheterization procedures. This
      method has proved to be highly effective, and few complications have been
      reported. Specifically, native arterial thrombosis, although recognized as a
      severe complication, has been mentioned only briefly in the literature. We
      present a case of the successful management of native arterial thrombosis after
      attempted percutaneous thrombin injection of a chronic external iliac artery
      pseudoaneurysm. This case serves to illustrate the risk factors for this
      complication and the treatment options once it occurs. The success of this
      treatment with acute iatrogenic femoral pseudoaneurysms may not necessarily
      translate into similar success in other anatomic locations and clinical
      situations.

PMID- 11331855
TI  - Perinatal inferior vena cava thrombosis and absence of the infrarenal inferior
      vena cava.
AB  - We report a case of infrarenal absence of the inferior vena cava (IVC) presenting
      as a major iliofemoral deep venous thrombosis in an adolescent. This is the first
      report of infrarenal IVC absence in which IVC thrombosis has been demonstrated in
      the perinatal period. We propose an association between perinatal IVC thrombosis
      and subsequent infrarenal IVC absence. In addition, the case demonstrates the
      importance of assessment for anatomical anomalies in patients presenting with
      apparently idiopathic deep venous thrombosis.

PMID- 11331856
TI  - Epithelioid hemangioendothelioma of the common femoral vein: Case report and
      review of the literature.
AB  - A young competitive skier had venous claudication. A stenosis of the left common
      femoral vein was revealed by means of an examination. Exploration and vein patch
      angioplasty were performed, and because of both the unusual appearance (focal
      thickening of vein wall) and the unclear etiology of the lesion, frozen and
      permanent sections of the wall were obtained. Epithelioid hemangioendothelioma, a
      rare intravascular sarcoma, was revealed by means of an examination of the
      permanent sections. Two additional procedures were required to completely excise
      the epithelioid hemangioendothelioma. We discuss these rare vascular malignancies
      and include a review of the available literature. Also, oncologic principles
      important in both the diagnosis and therapy of intravascular sarcomas are
      discussed.

PMID- 11331857
TI  - Intravascular lipoma of the left common femoral vein.
AB  - Lipomatous tumors of the heart and major central veins are unusual pathologic
      findings. We report an intravascular lipoma arising directly from the wall of the
      left common femoral vein (LCFV) in a patient who had progressive left leg
      swelling and in whom a deep venous thrombosis in the LCFV was initially
      diagnosed. this is the first case report if such a tumor in the literature. the
      computed tomography, magnetic resonance imaging, and intraoperative features are
      presented. the procedure of tumor excision and venous reconstruction with a
      cadaveric allograft is described.

PMID- 11331858
TI  - Complications in subfascial endoscopic perforating vein surgery: a report of two
      cases.
AB  - Subfascial endoscopic perforating vein surgery is a safe method for the division
      of incompetent perforating veins. Nevertheless, we report two cases with
      unfortunate complications: the posterior tibial artery and tibial nerve were
      damaged during the procedures. In one patient this resulted in a reintervention,
      but in both patients it resulted in permanent discomfort. We then present a
      guideline that may prevent damage to these critical structures.

PMID- 11331859
TI  - Successful reconstruction of stripped superficial femoral vein.
AB  - A 69-year-old man who had hemorrhagic shock after inadvertent stripping of the
      right superficial femoral-popliteal vein during surgery for greater saphenous
      vein varicosis in another hospital was referred to us. Phlebography revealed a
      ruptured popliteal vein with intact profunda femoris and common femoral veins.
      The stripped superficial femoral-popliteal vein brought in a jar was reimplanted.
      Phlebography performed during the patient's follow-up visits in our outpatient
      clinic 11 months postoperatively showed a patent femoral vein.

PMID- 11331860
TI  - An anterior tibial artery aneurysm in a patient with neurofibromatosis.
AB  - Von Recklinghausen's Type 1 neurofibromatosis (NF) is a genetic disorder of
      neuroectodermal tissue. Arterial involvement has also been recognized. Stenotic
      lesions predominate, but aneurysms have been documented as well. Aortoiliac,
      visceral, and cervical aneurysms are well represented in the literature. Rarely
      noted, however, have been peripheral aneurysms. Typically in more proximal
      vessels, subclavian, femoral, and popliteal aneurysms have been mentioned. We
      present the case of a patient with type 1 NF and an anterior tibial artery
      aneurysm that was subsequently resected. neurofibromatous invasion of the vessel
      was confirmed by means of pathological tests. We think this is the first reported
      case of a tibial artery aneurysm associated with NF.

PMID- 11331861
TI  - Thoracic outlet syndrome caused by first rib hemangioma.
AB  - We report a case of first rib hemangioma that caused thoracic outlet syndrome. A
      50-year-ole woman who was admitted to our hospital with a clinical diagnosis of
      thoracic outlet syndrome presented with fullness and easy fatigue of her right
      arm. Her right arm discomfort was associated with intermittent engorgement of
      superficial veins over the shoulder girdle. A chest radiograph revealed an
      enlargement of the anterior aspect of the first rib with fine bony
      trabeculations. Computed tomography scan showed contrast enhancement over the
      enlarged rib. Our tentative preoperative diagnosis was a benign first rib
      hypertrophic change, such as an old fracture with exuberant callus formation. A
      right-arm venogram revealed a patent subclavian vein with an extrinsic
      compression, which occluded on arm abduction. The findings of neural conduction
      studies of both upper extremities were symmetric and normal. The patient agreed
      to surgery because of the occlusive condition of the subclavian vein on arm
      abduction and progressive arm weakness in recent months. Segmental transection of
      the offending portion of the enlarged first rib was complicated by difficulty in
      isolating the whole length of the compressed but normal-appearing subclavian vein
      by our initial transaxillary and infraclavicular approaches because the medial
      aspect of the subclavian vein was obstructed by the enlarged first rib, which
      extended medially to the junction of the right jugular and subclavian veins.
      Successful segmental transection of the enlarged first rib was finally
      accomplished by combined transaxillary, infraclavicular, and supraclavicular
      approaches. A moderate amount of rib bleeding from resection ends was noted
      during segmental resection of the enlarged first rib, resulting in local hematoma
      formation. A 470-mL bloody discharge was collected from the vacuum ball inserted
      via the transaxillary route during her 12-day hospitalization. Pathologic
      examination revealed an intraosseous hemangioma. The patient had a prolonged
      course to partial recovery of her arm numbness, but signs of venous compression
      were much improved at 6 months' follow-up. Although hemangioma is benign, its
      hypervascular nature may cause catastrophic intraoperative bleeding.

PMID- 11331862
TI  - Carotid endarterectomy in rare bilateral carotid-vertebral anastomosis.
AB  - In the embryo, the anterior and the posterior cerebral circulations are connected
      by several longitudinal anastomotic vessels. These anastomoses disappear
      progressively, until the carotid and vertebrobasilar systems are connected only
      by a pair of posterior communicating arteries. These embryonal anastomoses rarely
      persist in adults and may have an important physiologic role during carotid
      surgery. We report a case in which a patient with bilateral embryonal carotid
      vertebral anastomoses underwent right carotid endarterectomy for asymptomatic
      internal carotid stenosis.

PMID- 11331863
TI  - Ruptured false abdominal aortic aneurysm during pregnancy: Caesarean delivery
      followed by aortic reconstruction.
AB  - We describe a case of a successfully treated ruptured abdominal aortic aneurysm
      during pregnancy. The importance of close clinical follow-up after any aortic
      reconstructions is highlighted.

PMID- 11331864
TI  - A human cadaveric circulation model.
AB  - Although endovascular techniques have achieved widespread acceptance, a suitable
      model for device development and physician training has not been available.
      Plastic models of the arterial tree and live animal models have significant
      limitations. Arterial-to-arterial flow is established in fresh frozen human
      cadavers after a simple thrombolytic process to achieve a more realistic model
      for endovascular device testing and training. Circulation can be established
      through most of the arterial system, including the cerebral, aortoiliac, and
      extremity vessels. This model offers antegrade flow in human arterial anatomy and
      has been used successfully for physician training and device development.

PMID- 11331865
TI  - Structural failure of first-generation, polyester, double-velour, knitted
      prostheses.

PMID- 11331866
TI  - Regarding "Phosphorus 31 nuclear magnetic resonance spectroscopy suggests a
      mitochondrial defect in claudicating skeletal muscle".

PMID- 11331868
TI  - Regarding "High endogenous estradiol is associated with increased venous
      distensibility and clinical evidence of varicose veins in menopausal women".

PMID- 11331870
TI  - Regulation of the PH-domain-containing tyrosine kinase Etk by focal adhesion
      kinase through the FERM domain.
AB  - Etk/BMX, a member of the Btk family of tyrosine kinases, is highly expressed in
      cells with great migratory potential, including endothelial cells and metastatic
      carcinoma cell lines. Here, we present evidence that Etk is involved in integrin
      signalling and promotes cell migration. The activation of Etk by extracellular
      matrix proteins is regulated by FAK through an interaction between the PH domain
      of Etk and the FERM domain of FAK. The lack of Etk activation by extracellular
      matrix in FAK-null cells could be restored by co-transfection with wild-type FAK.
      Disrupting the interaction between Etk and FAK diminished the cell migration
      promoted by either kinase. Furthermore, inhibiting Etk expression in metastatic
      carcinoma cell lines with an antisense oligonucleotide blocks integrin-mediated
      migration of these cells. Taken together, our data indicate the essential role of
      the interaction of the PH domain of Etk and the FERM domain of FAK in integrin
      signalling.

PMID- 11331871
TI  - Stabilization of p53 by p14ARF without relocation of MDM2 to the nucleolus.
AB  - The alternative product of the human INK4a/ARF locus, p14ARF, has the potential
      to act as a tumour suppressor by binding to and inhibiting the p53 antagonist
      MDM2. Current models propose that ARF function depends on its ability to
      sequester MDM2 in the nucleolus. Here we describe situations in which
      stabilization of MDM2 and p53 occur without relocalization of endogenous MDM2
      from the nucleoplasm. Conversely, forms of ARF that do not accumulate in the
      nucleolus retain the capacity to stabilize MDM2 and p53. We therefore propose
      that nucleolar localization is not essential for ARF function but may enhance the
      availability of ARF to inhibit MDM2.

PMID- 11331872
TI  - ERK induces p35, a neuron-specific activator of Cdk5, through induction of Egr1.
AB  - The classical mitogen-activated protein kinase (MAPK; also known as extracellular
      signal-regulated kinase), ERK cascade has been shown to have a crucial role in
      cell proliferation and differentiation. In PC12 cells, sustained activation of
      ERK induced by nerve-growth factor (NGF) is essential for neuronal
      differentiation. However, downstream targets of ERK that are essential for
      neuronal differentiation have not been defined. Here we show that NGF induces
      strong, sustained expression of p35, the neuron-specific activator of cyclin
      dependent kinase 5 (Cdk5), through activation of the ERK pathway. The induced
      kinase activity of Cdk5 is required for NGF-induced neurite outgrowth. Our
      results indicate that sustained activation of ERK is necessary and sufficient for
      strong induction of p35. Furthermore, the transcription factor Egr1, is induced
      by NGF through the ERK pathway and mediates induction of p35 by ERK. Our results
      thus define an essential signalling pathway, downstream of ERK/MAPK, that leads
      to neuronal differentiation.

PMID- 11331873
TI  - Tyrosine-phosphorylated SOCS-3 inhibits STAT activation but binds to p120 RasGAP
      and activates Ras.
AB  - Suppressors of cytokine signalling (SOCS, also known as CIS and SSI) are encoded
      by immediate early genes that act in a feedback loop to inhibit cytokine
      responses and activation of 'signal transducer and activator of transcription'
      (STAT). Here we show that SOCS-3 is strongly tyrosine-phosphorylated in response
      to many growth factors, including interleukin-2 (IL-2), erythropoietin (EPO),
      epidermal growth factor (EGF) and platelet-derived growth factor (PDGF). The
      principal phosphorylation sites on SOCS-3 are residues 204 and 221 at the carboxy
      terminus, and upon phosphorylation tyrosine 221 interacts with the Ras inhibitor
      p120 RasGAP. After IL-2 stimulation, phosphorylated SOCS-3 strongly inhibits
      STAT5 activation but, by binding to RasGAP, maintains activation of extracellular
      signal-regulated kinase (ERK). A tyrosine mutant of SOCS-3 still blocks STAT
      phosphorylation, but also strongly inhibits IL-2-dependent activation of ERK and
      cell proliferation. Moreover, it also inhibits EPO- and PDGF-induced
      proliferation and ERK activation. Therefore, although SOCS proteins inhibit
      growth-factor responses, tyrosine phosphorylation of SOCS-3 can ensure cell
      survival and proliferation through the Ras pathway.

PMID- 11331874
TI  - Force and focal adhesion assembly: a close relationship studied using elastic
      micropatterned substrates.
AB  - Mechanical forces play a major role in the regulation of cell adhesion and
      cytoskeletal organization. In order to explore the molecular mechanism underlying
      this regulation, we have investigated the relationship between local force
      applied by the cell to the substrate and the assembly of focal adhesions. A novel
      approach was developed for real-time, high-resolution measurements of forces
      applied by cells at single adhesion sites. This method combines micropatterning
      of elastomer substrates and fluorescence imaging of focal adhesions in live cells
      expressing GFP-tagged vinculin. Local forces are correlated with the orientation,
      total fluorescence intensity and area of the focal adhesions, indicating a
      constant stress of 5.5 +/- 2 nNmicrom(-2). The dynamics of the force-dependent
      modulation of focal adhesions were characterized by blocking actomyosin
      contractility and were found to be on a time scale of seconds. The results put
      clear constraints on the possible molecular mechanisms for the mechanosensory
      response of focal adhesions to applied force.

PMID- 11331875
TI  - Caveolar endocytosis of simian virus 40 reveals a new two-step vesicular
      transport pathway to the ER.
AB  - Simian virus 40 (SV40) is unusual among animal viruses in that it enters cells
      through caveolae, and the internalized virus accumulates in a smooth endoplasmic
      reticulum (ER) compartment. Using video-enhanced, dual-colour, live fluorescence
      microscopy, we show the uptake of individual virus particles in CV-1 cells. After
      associating with caveolae, SV40 leaves the plasma membrane in small, caveolin-1
      containing vesicles. It then enters larger, peripheral organelles with a non
      acidic pH. Although rich in caveolin-1, these organelles do not contain markers
      for endosomes, lysosomes, ER or Golgi, nor do they acquire ligands of clathrin
      coated vesicle endocytosis. After several hours in these organelles, SV40 is
      sorted into tubular, caveolin-free membrane vesicles that move rapidly along
      microtubules, and is deposited in perinuclear, syntaxin 17-positive, smooth ER
      organelles. The microtubule-disrupting agent nocodazole inhibits formation and
      transport of these tubular carriers, and blocks viral infection. Our results
      demonstrate the existence of a two-step transport pathway from plasma-membrane
      caveolae, through an intermediate organelle (termed the caveosome), to the ER.
      This pathway bypasses endosomes and the Golgi complex, and is part of the
      productive infectious route used by SV40.

PMID- 11331876
TI  - WIP regulates N-WASP-mediated actin polymerization and filopodium formation.
AB  - Induction of filopodia is dependent on activation of the small GTPase Cdc42 and
      on neural Wiskott-Aldrich-syndrome protein (N-WASP). Here we show that WASP
      interacting protein (WIP) interacts directly with N-WASP and actin. WIP retards N
      WASP/Cdc42-activated actin polymerization mediated by the Arp2/3 complex, and
      stabilizes actin filaments. Microinjection of WIP into NIH 3T3 fibroblasts
      induces filopodia; this is inhibited by microinjection of anti-N-WASP antibody.
      Microinjection of anti-WIP antibody inhibits induction of filopodia by
      bradykinin, by an active Cdc42 mutant (Cdc42(V12)) and by N-WASP. Our results
      indicate that WIP and N-WASP may act as a functional unit in filopodium
      formation, which is consistent with their role in actin-tail formation in cells
      infected with vaccinia virus or Shigella.

PMID- 11331877
TI  - Regulation of transport of the dopamine D1 receptor by a new membrane-associated
      ER protein.
AB  - Many structural determinants for G protein-coupled receptor (GPCR) functions have
      been defined, but little is known concerning the regulation of their transport
      from the endoplasmic reticulum (ER) to the cell surface. Here we show that a
      carboxy-terminal hydrophobic motif, FxxxFxxxF, which is highly conserved among
      GPCRs, functions independently as an ER-export signal for the dopamine D1
      receptor. A newly identified ER-membrane-associated protein, DRiP78, binds to
      this motif. Overexpression or sequestration of DRiP78 leads to retention of D1
      receptors in the ER, reduced ligand binding, and a slowdown in the kinetics of
      receptor glycosylation. Our results indicate that DRiP78 may regulate the
      transport of a GPCR by binding to a specific ER-export signal.

PMID- 11331878
TI  - Trp2 regulates entry of Ca2+ into mouse sperm triggered by egg ZP3.
AB  - In many cells, receptor activation initiates sustained Ca2+ entry which is
      critical in signal transduction. Mammalian transient receptor potential (Trp)
      proteins, which are homologous to the Drosophila photoreceptor-cell Trp protein,
      have emerged as candidate subunits of the ion channels that mediate this influx.
      As a consequence of overexpression, these proteins produce cation currents that
      open either after depletion of internal Ca2+ stores or through receptor
      activation. However, determining the role of endogenous Trp proteins in signal
      transduction is complicated by the absence of selective antagonists. Here we
      examine Trp function during sperm-egg interaction. The sperm acrosome reaction is
      a Ca2+-dependent secretory event that must be completed before fertilization. In
      mammals, exocytosis is triggered during gamete contact by ZP3, a glycoprotein
      constituent of the egg's extracellular matrix, or zona pellucida (ZP). ZP3
      activates trimeric G proteins and phospholipase C and causes a transient Ca2+
      influx into sperm through T-type Ca2+ channels. These early responses promote a
      second Ca2+-entry pathway, thereby producing sustained increases in intracellular
      Ca2+ concentration ([Ca2+]i) that drive acrosome reactions. Our results show that
      Trp2 is essential for the activation of sustained Ca2+ influx into sperm by ZP3.

PMID- 11331879
TI  - A 'hot-spot' mutation alters the mechanical properties of keratin filament
      networks.
AB  - Keratins 5 and 14 polymerize to form the intermediate filament network in the
      progenitor basal cells of many stratified epithelia including epidermis, where it
      provides crucial mechanical support. Inherited mutations in K5 or K14 result in
      epidermolysis bullosa simplex (EBS), a skin-fragility disorder. The impact that
      such mutations exert on the intrinsic mechanical properties of K5/K14 filaments
      is unknown. Here we show, by using differential interference contrast microscopy,
      that a 'hot-spot' mutation in K14 greatly reduces the ability of reconstituted
      mutant filaments to bundle under crosslinking conditions. Rheological assays
      measure similar small-deformation mechanical responses for crosslinked solutions
      of wild-type and mutant keratins. The mutation, however, markedly reduces the
      resilience of crosslinked networks against large deformations. Single-particle
      tracking, which probes the local organization of filament networks, shows that
      the mutant polymer exhibits highly heterogeneous structures compared to those of
      wild-type filaments. Our results indicate that the fragility of epithelial cells
      expressing mutant keratin may result from an impaired ability of keratin polymers
      to be crosslinked into a functional network.

PMID- 11331880
TI  - New protease inhibitors prevent gamma-secretase-mediated production of Abeta40/42
      without affecting Notch cleavage.
AB  - We have designed new non-peptidic potential inhibitors of gamma-secretase and
      examined their ability to prevent production of amyloid-beta 40 (Abeta40) and
      Abeta42 by human cells expressing wild-type and Swedish-mutant beta-amyloid
      precursor protein (betaAPP). Here we identify three such agents that markedly
      reduce recovery of both Abeta40 and Abeta42 produced by both cell lines, and
      increase that of C99 and C83, the carboxy-terminal fragments of betaAPP that are
      derived from beta-and alpha-secretase, respectively. Furthermore, we show that
      these inhibitors do not affect endoproteolysis of endogenous or overexpressed
      presenilins. These inhibitors are totally unable to affect the mDeltaEnotch-1
      cleavage that leads to generation of the Notch intracellular domain (NICD). These
      represent the first non-peptidic inhibitors that are able to prevent gamma
      secretase cleavage of betaAPP without affecting processing of mDeltaEnotch-1 or
      endoproteolysis of presenilins. The distinction between these two proteolytic
      events, which are both prevented by disruption of presenilin genes, indicates
      that although they are intimately linked with betaAPP and Notch maturation,
      presenilins are probably involved in the control of maturation processes upstream
      of enzymes that cleave gamma-secretase and Notch.

PMID- 11331881
TI  - PDGF-D is a specific, protease-activated ligand for the PDGF beta-receptor.
AB  - The term 'platelet-derived growth factor' (PDGF) refers to a family of disulphide
      bonded dimeric isoforms that are important for growth, survival and function in
      several types of connective tissue cell. So far, three different PDGF chains have
      been identified - the classical PDGF-A and PDGF-B and the recently identified
      PDGF-C. PDGF isoforms (PDGF-AA, AB, BB and CC) exert their cellular effects by
      differential binding to two receptor tyrosine kinases. The PDGF alpha-receptor
      (PDGFR-alpha) binds to all three PDGF chains, whereas the beta-receptor (PDGFR
      beta) binds only to PDGF-B. Gene-targeting studies using mice have shown that the
      genes for PDGF-A and PDGF-B, as well as the two PDGFR genes, are essential for
      normal development. Furthermore, overexpression of PDGFs is linked to different
      pathological conditions, including malignancies, atherosclerosis and
      fibroproliferative diseases. Here we have identify and characterize a fourth
      member of the PDGF family, PDGF-D. PDGF-D has a two-domain structure similar to
      PDGF-C and is secreted as a disulphide-linked homodimer, PDGF-DD. Upon limited
      proteolysis, PDGF-DD is activated and becomes a specific agonistic ligand for
      PDGFR-beta. PDGF-DD is the first known PDGFR-beta-specific ligand, and its unique
      receptor specificity indicates that it may be important for development and
      pathophysiology in several organs.

PMID- 11331882
TI  - PDGF-D, a new protease-activated growth factor.
AB  - Platelet-derived growth factor (PDGF) has been directly implicated in
      developmental and physiological processes, as well as in human cancer, fibrotic
      diseases and arteriosclerosis. The PDGF family currently consists of at least
      three gene products, PDGF-A, PDGF-B and PDGF-C, which selectively signal through
      two PDGF receptors (PDGFRs) to regulate diverse cellular functions. After two
      decades of searching, PDGF-A and B were the only ligands identified for PDGFRs.
      Recently, however, database mining has resulted in the discovery of a third
      member of the PDGF family, PDGF-C, a functional analogue of PDGF-A that requires
      proteolytic activation. PDGF-A and PDGF-C selectively activate PDGFR-alpha,
      whereas PDGF-B activates both PDGFR-alpha and PDGFR-beta. Here we identify and
      characterize a new member of the PDGF family, PDGF D, which also requires
      proteolytic activation. Recombinant, purified PDGF-D induces DNA synthesis and
      growth in cells expressing PDGFRs. In cells expressing individual PDGFRs, PDGF-D
      binds to and activates PDGFR-beta but not PDGFR-alpha. However, in cells
      expressing both PDGFRs, PDGF-D activates both receptors. This indicates that
      PDGFR-alpha activation may result from PDGFR-alpha/beta heterodimerization.

PMID- 11331883
TI  - Fission yeast Bub1 is essential in setting up the meiotic pattern of chromosome
      segregation.
AB  - In meiosis, sister-chromatids move to the same spindle pole during the first
      division (MI) and to opposite poles during the second division (MII). This
      requires that MI sister kinetochores are co-orientated and form an apparent
      single functional unit that only interacts with microtubules from one pole, and
      that sister-chromatids remain associated through their centromeres until anaphase
      II. Here we investigate the function of Bub1 and Mad2, which are components of
      the mitotic-spindle checkpoint, on chromosome segregation during meiosis. Both
      proteins are required to prevent the occurrence of non-disjunction events in MI,
      which is consistent with recent findings that components of the mitotic-spindle
      checkpoint also operate during meiosis. However, Bub1 has several functions that
      are not shared with Mad2. When the bub1 gene is deleted, sister chromatids often
      move to opposite spindle poles during MI, indicating that sister kinetochores are
      disunited. Furthermore, the cohesin Rec8 is never retained at centromeres at
      anaphase I and sister-chromatid cohesion is lost. Our results show that Bub1,
      besides its functions in monitoring chromosome attachment, is essential for two
      other significant aspects of MI - unification of sister kinetochores and
      retention of centromeric cohesion.

PMID- 11331887
TI  - Presenilin and the UPR.

PMID- 11331886
TI  - Controversy and debate: the nature of science.

PMID- 11331884
TI  - Activation of EphA receptor tyrosine kinase inhibits the Ras/MAPK pathway.
AB  - Interactions between Eph receptor tyrosine kinases (RTKs) and membrane-anchored
      ephrin ligands critically regulate axon pathfinding and development of the
      cardiovascular system, as well as migration of neural cells. Similar to other
      RTKs, ligand-activated Eph kinases recruit multiple signalling and adaptor
      proteins, several of which are involved in growth regulation. However, in
      contrast to other RTKs, activation of Eph receptors fails to promote cell
      proliferation or to transform rodent fibroblasts, indicating that Eph kinases may
      initiate signalling pathways that are distinct from those transmitted by other
      RTKs. Here we show that stimulation of endogenous EphA kinases with ephrin-A1
      potently inhibits the Ras/MAPK cascade in a range of cell types, and attenuates
      activation of mitogen-activated protein kinase (MAPK) by receptors for platelet
      derived growth factor (PDGF), epidermal growth factor (EGF) and vascular
      endothelial growth factor (VEGF). In prostatic epithelial cells and endothelial
      cells, but not fibroblasts, treatment with ephrin-A1 inhibits cell proliferation.
      Our results identify EphA kinases as negative regulators of the Ras/MAPK pathway
      that exert anti-mitogenic functions in a cell-type-specific manner.

PMID- 11331888
TI  - More light on decoding darkness.

PMID- 11331889
TI  - Centrosomes as command centres for cellular control.

PMID- 11331890
TI  - G-protein activation live.

PMID- 11331891
TI  - Caveolae on the move.

PMID- 11331893
TI  - Getting a grip: new insights for cell adhesion and traction.

PMID- 11331894
TI  - Integrating Myc and TGF-beta signalling in cell-cycle control.

PMID- 11331897
TI  - Mechanisms of epithelial fusion and repair.
AB  - One of the principal functions of any epithelium in the embryonic or adult
      organism is to act as a self-sealing barrier layer. From the earliest stages of
      development, embryonic epithelia are required to close naturally occurring holes
      and to fuse wherever two free edges are brought together, and at the simplest
      level that is precisely what the epidermis must do to repair itself wherever it
      is damaged. Parallels can be drawn between the artificially triggered epithelial
      movements of wound repair and the naturally occurring epithelial movements that
      shape the embryo during morphogenesis. Recent in vitro and in vivo wound-healing
      studies and analysis of paradigm morphogenetic movements in genetically tractable
      embryos, like those of Drosophila and Caenorhabditis elegans, have begun to
      identify both the signals that initiate these movements and the cytoskeletal
      machinery that drives motility. We are also gaining insight into the nature of
      the brakes and stop signals, and the mechanisms by which the confronting
      epithelial sheets knit together to form a seam.

PMID- 11331898
TI  - Coping with the inevitable: how cells repair a torn surface membrane.
AB  - Disruption of the cell plasma membrane is a commonplace occurrence in many
      mechanically challenging, biological environments. 'Resealing' is the emergency
      response required for cell survival. Resealing is triggered by Ca2+ entering
      through the disruption; this causes vesicles present in cytoplasm underlying the
      disruption site to fuse rapidly with one another (homotypically) and also with
      the adjacent plasma membrane (heterotypically/exocytotically). The large
      vesicular products of homotypic fusion are added as a reparative 'patch' across
      the disruption, when its resealing requires membrane replacement. The
      simultaneous activation of the local cytoskeleton supports these membrane fusion
      events. Resealing is clearly a complex and dynamic cell adaptation, and, as we
      emphasize here, may be an evolutionarily primitive one that arose shortly after
      the ancestral eukaryote lost its protective cell wall.

PMID- 11331899
TI  - Yesterday's polyploids and the mystery of diploidization.
AB  - Thirty years after Susumu Ohno proposed that vertebrate genomes are degenerate
      polyploids, the extent to which genome duplication contributed to the evolution
      of the vertebrate genome, if at all, is still uncertain. Sequence-level studies
      on model organisms whose genomes show clearer evidence of ancient polyploidy are
      invaluable because they indicate what the evolutionary products of genome
      duplication can look like. The greatest mystery is the molecular basis of
      diploidization, the evolutionary process by which a polyploid genome turns into a
      diploid one.

PMID- 11331900
TI  - The genetics and pathology of oxidative phosphorylation.
AB  - The mitochondrial oxidative phosphorylation (OXPHOS) system is the final
      biochemical pathway in the production of ATP. The OXPHOS system consists of five
      multiprotein complexes, the individual subunits of which are encoded either by
      the mitochondrial or by the nuclear genome. Defects in the OXPHOS system result
      in devastating, mainly multisystem, diseases, and recent years have seen the
      description of the underlying genetic mutations in mitochondrial and nuclear
      genes. Advances in this arena have profited from progress in various genome
      projects, as well as improvements in our ability to create relevant animal
      models.

PMID- 11331901
TI  - Ancient DNA.
AB  - DNA that has been recovered from archaeological and palaeontological remains
      makes it possible to go back in time and study the genetic relationships of
      extinct organisms to their contemporary relatives. This provides a new
      perspective on the evolution of organisms and DNA sequences. However, the field
      is fraught with technical pitfalls and needs stringent criteria to ensure the
      reliability of results, particularly when human remains are studied.

PMID- 11331902
TI  - Meiotic recombination hot spots and cold spots.
AB  - Meiotic recombination events are distributed unevenly throughout eukaryotic
      genomes. This inhomogeneity leads to distortions of genetic maps that can hinder
      the ability of geneticists to identify genes by map-based techniques. Various
      lines of evidence, particularly from studies of yeast, indicate that the
      distribution of recombination events might reflect, at least in part, global
      features of chromosome structure, such as the distribution of modified
      nucleosomes.

PMID- 11331903
TI  - Mapping quantitative trait loci in plants: uses and caveats for evolutionary
      biology.
AB  - Gregor Mendel was either clever or lucky enough to study traits of simple
      inheritance in his pea plants; however, many plant characters of interest to
      modern geneticists are decidedly complex. Understanding the genetic basis of such
      complex, or quantitative, traits requires a combination of modern molecular
      genetic techniques and powerful statistical methods. These approaches have begun
      to give us insight into understanding the evolution of complex traits both in
      crops and in wild plants.

PMID- 11331904
TI  - The flexible genome.
AB  - A principal assumption underlying contemporary genetic analysis is that the
      normal function of a gene can be inferred directly from its mutant phenotype. The
      interactivity among genes that is now being revealed calls this assumption into
      question and indicates that there might be considerable flexibility in the
      capacity of the genome to respond to diverse conditions. The reservoir for much
      of this flexibility resides in the nonspecificity and malleability of gene
      action.

PMID- 11331905
TI  - Predicting adaptive evolution.
AB  - Phylogenetic trees reconstruct past evolution and can provide evidence of past
      evolutionary pressure on genes and on individual codons. In addition to tracing
      past evolutionary events, molecular phylogenetics might also be used to predict
      future evolution. Our ability to verify adaptive hypotheses using phylogenetics
      has broad implications for vaccine design, genomics and structural biology.

PMID- 11331906
TI  - Protecting genetic privacy.
AB  - This article outlines the arguments for and against new rules to protect genetic
      privacy. We explain why genetic information is different to other sensitive
      medical information, why researchers and biotechnology companies have opposed new
      rules to protect genetic privacy (and favour anti-discrimination laws instead),
      and discuss what can be done to protect privacy in relation to genetic-sequence
      information and to DNA samples themselves.

PMID- 11331907
TI  - Back in the water: the return of the inositol phosphates.
AB  - Following the discovery of inositol-1,4,5-trisphosphate as a second messenger,
      many other inositol phosphates were discovered in quick succession, with some
      understanding of their synthesis pathways and a few guesses at their possible
      functions. But then it all seemed to go comparatively quiet, with an explosion of
      interest in the inositol lipids. Now the water-soluble phase is once again
      becoming a focus of interest. Old and new data point to a new vista of inositol
      phosphates, with functions in many diverse aspects of cell biology, such as ion
      channel physiology, membrane dynamics and nuclear signalling.

PMID- 11331908
TI  - Versatility of the mitochondrial protein import machinery.
AB  - The vast majority of mitochondrial proteins are synthesized in the cytosol and
      are imported into mitochondria by protein machineries located in the
      mitochondrial membranes. It has become clear that hydrophilic as well as
      hydrophobic preproteins use a common translocase in the outer mitochondrial
      membrane, but diverge to two distinct translocases in the inner membrane. The
      translocases are dynamic, high-molecular-weight complexes that have to provide
      specific means for the recognition of preproteins, channel formation and
      generation of import-driving forces.

PMID- 11331909
TI  - Protein targeting by the twin-arginine translocation pathway.
AB  - The twin-arginine translocation pathway operates in the thylakoid membrane of
      chloroplasts and in the plasma membrane of most free-living bacteria. Its main
      function is to transport fully folded proteins across the membrane. Three
      important tat genes have been identified and the sequences of the encoded
      proteins, together with the unusual properties of the pathway, indicate that the
      Tat system is completely different from other protein translocases.

PMID- 11331910
TI  - The life cycle of the peroxisome.
AB  - Peroxisomes are highly adaptable organelles that carry out oxidative reactions.
      Distinct cellular machineries act together to coordinate peroxisome formation,
      growth, division, inheritance, turnover, movement and function. Soluble and
      membrane-associated components of these machineries form complex networks of
      physical and functional interactions that provide supramolecular control of the
      precise dynamics of peroxisome biogenesis.

PMID- 11331911
TI  - Rap1 signalling: adhering to new models.
AB  - Ras-like GTPases are ubiquitously expressed, evolutionarily conserved molecular
      switches that couple extracellular signals to various cellular responses. Rap1,
      the closest relative of Ras, has attracted much attention because of the
      possibility that it regulates Ras-mediated signalling. Rap1 is activated by
      extracellular signals through several regulatory proteins, and it might function
      in diverse processes, ranging from modulation of growth and differentiation to
      secretion, integrin-mediated cell adhesion and morphogenesis.

PMID- 11331912
TI  - A weak signal for strong responses: interferon-alpha/beta revisited.
AB  - Biological systems have acquired adaptability and robustness against rapid
      environmental changes. A typical example is the immune system, which eradicates
      invading pathogens such as viruses. Interferons alpha and beta, which are
      produced in response to viral infection, are essential components of this system
      but are also produced at low levels in the absence of infection. What is the
      purpose of the constitutive weak interferon-alpha/beta signal?

PMID- 11331913
TI  - The myosin swinging cross-bridge model.
AB  - No biological system has been studied by more diverse approaches than the actin
      based molecular motor myosin. Biophysics, biochemistry, physiology, classical
      genetics and molecular genetics have all made their contributions, and myosin is
      now becoming one of the best-understood enzymes in biology.

PMID- 11331914
TI  - Cell control by membrane-cytoskeleton adhesion.
AB  - The rates of mechanochemical processes, such as endocytosis, membrane extension
      and membrane resealing after cell wounding, are known to be controlled
      biochemically, through interaction with regulatory proteins. Here, I propose that
      these rates are also controlled physically, through an apparently continuous
      adhesion between plasma membrane lipids and cytoskeletal proteins.

PMID- 11331915
TI  - Role of AMPA receptor endocytosis in synaptic plasticity.
AB  - Activity-mediated changes in the strength of synaptic communication are important
      for the establishment of proper neuronal connections during development and for
      the experience-dependent modification of neural circuitry that is believed to
      underlie all forms of behavioural plasticity. Owing to the wide-ranging
      significance of synaptic plasticity, considerable efforts have been made to
      identify the mechanisms by which synaptic changes are triggered and expressed.
      New evidence indicates that one important expression mechanism of several long
      lasting forms of synaptic plasticity might involve the physical transport of AMPA
      type glutamate receptors in and out of the synaptic membrane. Here, we focus on
      the rapidly accumulating evidence that AMPA receptors undergo regulated
      endocytosis, which is important for long-term depression.

PMID- 11331916
TI  - Experimental models of Parkinson's disease.
AB  - Research into the pathogenesis of Parkinson's disease has been rapidly advanced
      by the development of animal models. Initial models were developed by using
      toxins that specifically targeted dopamine neurons, the most successful of which
      used 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, a toxin that causes
      parkinsonism in man. More recently, the identification of alpha-synuclein
      mutations as a rare cause of Parkinson's disease has led to the development of
      alpha-synuclein transgenic mice and Drosophila. Here, I discuss the merits and
      limitations of these different animal models in our attempts to understand the
      physiology of Parkinson's disease and to develop new therapies.

PMID- 11331917
TI  - Regulating proliferation during retinal development.
AB  - Recent studies have shown that components of the cell-cycle machinery can have
      diverse and unexpected roles in the retina. Cyclin-kinase inhibitors, for
      example, have been implicated as regulators of cell-fate decisions during
      histogenesis and reactive gliosis in the adult tissue after injury. Also, various
      mechanisms have been identified that can compensate for extra rounds of cell
      division when the normal timing of the cell-cycle exit is perturbed.
      Surprisingly, distinct components of the cell-cycle machinery seem to be used
      during different stages of development, and different organisms might rely on
      distinct pathways. Such detailed studies on the regulation of proliferation in
      complex multicellular tissues during development have not only advanced our
      knowledge of the ways in which proliferation is controlled, but might also help
      us to understand the degenerative disorders that are associated with gliosis and
      some types of tumorigenesis.

PMID- 11331918
TI  - Research and treatment approaches to depression.
AB  - Depression is a major cause of disability worldwide, but we know little about the
      underlying fundamental biology. Research is hindered by the difficulties of
      modelling a disorder of higher cognitive functions in animals. Depression can be
      understood as the interaction of genetic susceptibility and environmental
      factors; however, current classifications are purely descriptive. The complexity
      of this field is best approached by rigorous explorations of known candidate
      systems in conjunction with the use of genomic tools to discover new targets for
      antidepressants and to predict therapeutic outcomes.

PMID- 11331919
TI  - Neuropsychology of fear and loathing.
AB  - For over 60 years, ideas about emotion in neuroscience and psychology have been
      dominated by a debate on whether emotion can be encompassed within a single,
      unifying model. In neuroscience, this approach is epitomized by the limbic system
      theory and, in psychology, by dimensional models of emotion. Comparative research
      has gradually eroded the limbic model, and some scientists have proposed that
      certain individual emotions are represented separately in the brain. Evidence
      from humans consistent with this approach has recently been obtained by studies
      indicating that signals of fear and disgust are processed by distinct neural
      substrates. We review this research and its implications for theories of emotion.

PMID- 11331920
TI  - Cell therapy in Parkinson's disease - stop or go?
AB  - The results of the first double-blind placebo-controlled trial using grafts of
      embryonic tissue to treat Parkinson's disease have aroused widespread interest
      and debate about the future of cell replacement therapies. What are the key
      issues that need to be resolved and the directions in which this technology is
      likely to develop?

PMID- 11331921
TI  - Olfactory ensheathing cells - another miracle cure for spinal cord injury?
AB  - Several recent publications describe remarkably promising effects of
      transplanting olfactory ensheathing cells as a potential future method to repair
      human spinal cord injuries. But why were cells from the nose transplanted into
      the spinal cord? What are olfactory ensheathing cells, and how might they produce
      these beneficial effects? And more generally, what do we mean by spinal cord
      injury? To what extent can we compare repair in an animal to repair in a human?

PMID- 11331923
TI  - Characteristics of colorectal cancer that produce positive immunochemical occult
      blood test results on stool obtained by digital rectal examination.
AB  - OBJECTIVE: To clarify the clinicopathological features of colorectal cancer that
      show positive results on an immunochemical fecal occult blood test of stool
      obtained by digital rectal examination. METHODS: In a cross-sectional study, 9952
      subjects received both an immunochemical fecal occult blood test of stool
      obtained by digital rectal examination and colonoscopy annually over a nine-year
      period of medical checkups; 64 patients with colorectal cancer were identified.
      The study subjects comprised 39 patients with colorectal cancer who had positive
      results (positive group) and 25 patients with colorectal cancer who had negative
      results (negative group) on an immunochemical fecal occult blood test of stool
      obtained by digital rectal examination. The positive and negative groups were
      compared in terms of their individual factors, such as site, size, Dukes
      classification and histological type of the cancer lesions. RESULTS: The
      prevalence of rectal cancers was higher in the positive group than in the
      negative group (P<0.05), but there were no differences between the two groups
      with respect to any other factors. CONCLUSIONS: These findings indicate that
      stool obtained during the digital rectal examination is unsuitable for detecting
      fecal occult blood, especially for the detection of proximal colon neoplasms.

PMID- 11331924
TI  - Colorectal cancer complicating Crohn's disease.
AB  - Some earlier studies have indicated that patients with inflammatory bowel
      disease, especially those with long-standing and extensive ulcerative colitis,
      have an increased risk of colorectal cancer. Moreover, others in tertiary care
      centres have suggested that patients with Crohn's disease also have a higher risk
      of colorectal cancer. Canadian data on colorectal cancer in Crohn's disease
      appear to be limited. For this investigation, a single clinician database of 877
      patients with Crohn's disease was used. Altogether, there were six patients with
      colorectal cancer (ie, overall rate of 0.7%). All of these patients were men with
      an initial diagnosis of Crohn's disease established at a mean age of
      approximately 28 years, with either ileocolonic disease or colonic disease alone,
      but not with ileal disease alone. Although there was a predominance of women in
      the overall study population (ie, 56.1%), no women developed colorectal cancer.
      The clinical behaviour of Crohn's disease was classified as nonstricturing in all
      six patients with colorectal cancer, but in two patients, Crohn's disease was
      complicated by a perirectal abscess or a fistula. All cancers were located in the
      rectum and were diagnosed 30 years, 22 years, seven years, 18 years, 20 years and
      40 years after Crohn's disease was initially diagnosed. In three patients, the
      cancer was detected in a residual rectal stump after a partial colon resection at
      least 10 years earlier. In five patients, localized extension of disease through
      the serosa, nodal or distant metastases (ie, liver, lung) was found at the time
      of cancer diagnosis; two patients have since died. The present study confirms
      that Crohn's disease involving the colon may be a possible risk factor for the
      development of colorectal cancer, at least in younger men, but, in this study,
      not in women. However, part of this increased risk in men may have been related
      to the presence of a rectal stump, rather than to Crohn's disease per se.

PMID- 11331925
TI  - Laparoscopic versus open bowel resection for Crohn's disease.
AB  - BACKGROUND: Laparoscopic bowel resection is an alternative to open surgery for
      patients with Crohn's disease requiring surgical resection. The present report
      describes a seven-year experience with the laparoscopic treatment of Crohn's
      disease compared with the open technique in a tertiary Canadian centre. PATIENTS
      AND METHODS: A retrospective analysis of 61 consecutive patients undergoing
      elective resection for Crohn's disease was carried out between October 1992 and
      June 1999. This analysis included 32 laparoscopic resections (mean age 33 years)
      and 29 open resections (mean age 42 years). Patient demographics were compared,
      as well as short and long term outcomes after surgery (mean follow-up 39 months).
      RESULTS: Patients in the laparoscopic group were younger and had fewer previous
      bowel surgeries than patients who had open resections. Indications for surgery
      and operative times were similar between the groups. Patients who underwent
      laparoscopic resections required fewer doses of narcotic analgesics. The
      resumption of bowel function after surgery, and tolerance of a clear liquid and
      solid diet was quicker in the laparoscopic group. Patients who underwent
      laparoscopic resections had significantly shorter hospital stays than those who
      underwent open resections. Fifteen patients (48.4%) in the laparoscopic group
      experienced recurrence of disease compared with 13 patients (44.8%) in the open
      group. In both groups, the most common site of recurrence was at the anastomosis.
      The disease-free interval was the same length for both groups (23.9+/-17.3 months
      for the laparoscopic resection patients compared with 23.9+/-20.2 months for the
      open resection patients; P=1.00). CONCLUSIONS: Laparoscopic resection for Crohn's
      disease can be performed safely and effectively. Quicker resumption of oral
      feeds, less postoperative pain and earlier discharge from hospital are advantages
      of the laparoscopic method. No differences in the recurrence rate or the disease
      free interval were noted.

PMID- 11331926
TI  - In vivo gluten challenge in celiac disease.
AB  - In vivo gluten challenge has been used since the early 1950s to study the role of
      cereal fractions in celiac disease. While early studies relied on crude
      indicators of celiac toxicity, the advent of jejunal biopsy and sophisticated
      immunohistochemical techniques has allowed accurate studies to be performed.
      Studies to determine the nature of the cereal component that is toxic to patients
      with celiac disease have concentrated on wheat because of its nutritional
      importance. A number of in vitro studies indicated the presence of one or more
      celiac-activating epitopes with the N-terminus of the A-gliadin molecule. In vivo
      challenge with three synthetic peptides subsequently indicated the toxicity of a
      peptide corresponding to amino acids 31 to 49 of A-gliadin. In vivo gluten
      challenge is the gold standard for the assessment of celiac toxicity; however,
      jejunal biopsy is a relatively invasive procedure, thus, other methods have been
      investigated. Direct infusion of the rectum with gluten has been shown to result
      in an increase in mucosal intraepithelial lymphocytes, occurring only in celiac
      patients. This method has been used to study the celiac toxicity of gliadin
      subfractions. The in vitro technique of small intestinal biopsy organ culture is
      also a useful tool and appears to give the same results as in vivo challenge. The
      importance of tiny amounts of gliadin in the diet, such as that which occurs in
      wheat starch, has been studied by in vivo challenge; this technique has clarified
      the position of oats in the gluten-free diet. Several studies suggest that this
      cereal may be included in the diet of most adult celiac patients. Studies of the
      transport of gliadin across the enterocyte following ingestion or challenge
      suggest that gliadin may be metabolized by a different pathway in celiac disease.
      This could result in an abnormal presentation to the immune system, triggering a
      pathogenic rather than a tolerogenic response.

PMID- 11331927
TI  - Update on the role of H pylori infection in gastrointestinal disorders.
AB  - Infection with Helicobacter pylori is accepted as the primary cause of peptic
      ulcer disease, and there is evidence to suggest its role in other
      gastrointestinal disorders. An estimated 20% to 40% of the Canadian population is
      infected with H pylori; however, clinically relevant disease is present in only
      approximately 10% to 20% of these individuals. Therefore, it is crucial to
      identify the diseases for which eradication of H pylori is beneficial to ensure
      that patients do not receive unnecessary treatment. In patients with ulcers
      induced by long term treatment with nonsteroidal anti-inflammatory drugs,
      preliminary results suggest that eradication of H pylori may reduce the risk of
      peptic ulcer bleeding. Furthermore, a benefit has been observed for the
      eradication of H pylori before patients commence therapy with a nonsteroidal anti
      inflammatory drug. An association between the presence of H pylori and specific
      dyspeptic symptoms has yet to be established; however, there may be a subset of
      patients with functional dyspepsia who benefit from the eradication of H pylori.
      The relationship between gastroesophageal reflux disorder and H pylori infection
      remains unclear. In Canada, the recommended therapy for the eradication of H
      pylori is seven days of twice-daily treatment with a proton pump inhibitor,
      clarithromycin, and amoxicillin or metronidazole. Although the proton pump
      inhibitors are treated as a class for use in these regimens, there is suggestion
      that a faster onset of action may lead to a higher rate of eradication.

PMID- 11331928
TI  - Perioperative radiotherapy in the management of rectal cancer.
AB  - Surgery for rectal cancer has resulted in unacceptably high local failure rates,
      and substantial morbidity and mortality. In an attempt to reduce the high
      frequency of local recurrence, perioperative radiotherapy has been used
      extensively, alone or in combination with chemotherapy. The local recurrence rate
      has been reduced dramatically with the use of radiotherapy, and provided that the
      dose is high enough and given preoperatively, the reduction rate has been about
      50%. Despite that a higher dose is used in postoperative radiotherapy, the
      reduced recurrence rate is not that prominent. The reduced recurrence rate
      demonstrated after preoperative radiotherapy has a positive influence on
      survival, which has not been seen when radiotherapy is given postoperatively.
      However, when postoperative irradiation has been combined with chemotherapy, a
      survival benefit has been demonstrated. With modern radiation techniques,
      preoperative radiotherapy can be delivered without any substantial increase in
      postoperative mortality or morbidity, and a low rate of late toxicity, provided
      that the radiation technique is optimal. The main question is whether
      radiotherapy is necessary, provided that surgery is optimized. With standard
      surgery, the average local recurrence rate is 29% in all reported controlled
      trials. With optimal surgery, from institutional series, this figure is about
      10%. Other questions to be answered are whether superfractionated or standard
      fractionation should be used in radiotherapy and exactly to whom it should be
      given.

PMID- 11331929
TI  - Spontaneous peritonitis from perforation of the colon in collagenous colitis.
AB  - A 37-year-old woman presented with an acute abdomen following the onset of watery
      diarrhea. Spontaneous peritonitis was detected, along with evidence of a focal
      sigmoid colon perforation. Subsequent postoperative colonoscopic studies revealed
      collagenous colitis with a focal, deep, nongranulomatous ulcer in the sigmoid
      colon. Although the literature suggests that collagenous colitis tends to have a
      relatively 'benign' clinical course characterized by chronic or episodic watery
      diarrhea. Potentially serious and life- threatening complications may occur in
      this microscopic form of inflammatory bowel disease.

PMID- 11331930
TI  - Gastrointestinal mucormycosis in a renal transplant patient.
AB  - The clinical course and management of a rare case of gastrointestinal
      mucormycosis occurring in a renal transplant patient are presented. The diagnosis
      was made on pathological examination of surgically resected tissue from the
      colon, spleen and stomach. The patient did not survive the infection. To the best
      of our knowledge, this is the 11th reported case of gastrointestinal mucormycosis
      in a solid organ transplant patient. The pathophysiology, incidence and prognosis
      of this disease are discussed.

PMID- 11331931
TI  - Granulomatous cheilitis and Crohn's disease.
AB  - Granulomatous cheilitis is characterized by recurrent swelling of the labial
      tissues and granulomatous histology. Granulomatous cheilitis has been recognized
      as an early manifestation of Crohn's disease. It may follow, coincide with or
      precede the onset of Crohn's disease. The first case presented involved an
      extraintestinal manifestation of Crohn's disease, and the second case presented
      is of development of granulomatous cheilitis a year before the onset of
      symptomatic Crohn's disease. Although chronic granulomatous cheilitis is a very
      rare disorder, once it is diagnosed, the patient should be followed up carefully.
      These patients should be investigated for asymptomatic Crohn's disease either
      when the diagnosis of granulomatous cheilitis is confirmed or when
      gastrointestinal symptoms develop.

PMID- 11331932
TI  - Molecular mechanisms in renal and intestinal sulfate (re)absorption.

PMID- 11331933
TI  - Mg-dependent, Zn-ATPase: enzymatic characteristics, ion specificities and tissue
      distribution.
AB  - Mucosal crude microsomes, prepared from proximal rat small intestine, exhibited
      significant Mg-dependent, Zn-ATPase activity; Vmax = 23 micromoles Pi/mg
      protein/hr, Km = 160 nm, and Hill Coefficient, n = 1.5. Partial purification
      (approximately 10-fold) was achieved by detergent extraction, and centrifugation
      through 250 mm sucrose: Vmax = 268 units, Km = 1 nm, and n = 6. In partially
      purified preparations, the assay was linear with time to 60 min, and with protein
      concentration to 1 microg/300 microl. Activities at pH 8 and 8.5 were higher than
      at pH 7.2. The ATP Km was 0.7 mm, with an optimal ATP/Mg ratio of approximately
      2. Ca elicited ATPase activity but did not augment the Zn-dependent activity. In
      partially purified preparations, the homologous salts of Co, Cd, Cu, and Mn
      exhibited no detectable activity. Vanadate inhibition studies yielded two
      component kinetics with a Ki of 12 microm for the first component, and 96 microm
      for the second component, in partially purified preparations. Tissue distribution
      analyses revealed gradients of activity. In the proximal half of the small
      intestine, Mg/Zn activity increased progressively from crypt to villus tip. In
      long axis studies, this activity decreased progressively from proximal to distal
      small bowel.

PMID- 11331934
TI  - Functional effects of casein kinase I-catalyzed phosphorylation on lens cell-to
      cell coupling.
AB  - The functional consequence of the casein kinase I-catalyzed phosphorylation of
      the lens gap junctional protein connexin49 was investigated using a sheep primary
      lens cell culture system. To determine whether the phosphorylation of connexin49
      catalyzed by endogenous casein kinase I results in an altered junctional
      communication between lens cells, the effect of the casein kinase I-specific
      inhibitor CKI-7 on Lucifer Yellow dye transfer between cells in the lens culture
      was examined. Dye transfer was analyzed in cultures of different ages because we
      have demonstrated previously that the expression of connexin49 increases as the
      cultures age while that of connexin43, which is likely not a substrate for casein
      kinase I, has been shown to decrease [Yang & Louis (1999) Invest. Ophthalmol.
      Vis. Sci. 41: 2568-2564]. In 9-day old lens cultures, in which gap junctions are
      composed primarily of connexin43, CKI-7 had little effect on the rate of dye
      transfer between lens cells. In contrast, treatment of 15-day and 28-day old
      cultures with CKI-7 resulted in a significant increase in the rate of dye
      transfer. Thus, the extent of this CKI-7-dependent increase in cell-to-cell
      communication was positively correlated with the level of expression of
      connexin49, the major casein kinase I substrate in lens plasma membranes. These
      results suggest that the casein kinase I-catalyzed phosphorylation of connexin49
      decreases cell communication between connexin49-containing gap junctions in the
      lens.

PMID- 11331935
TI  - Effects of hyperglycemia and protein kinase C on connexin43 expression in
      cultured rat retinal pigment epithelial cells.
AB  - Previous results demonstrated that the intercellular communication mediated by
      gap junctions in retinal pigment epithelial (RPE) cells from the healthy Long
      Evans (LE) rat strain is higher than that from the dystrophic Royal College of
      Surgeons (RCS) rat strain. We examined connexin (Cx) expression in both cell
      types. At the mRNA level, a qualitatively similar expression pattern was found
      whereby Cx26, Cx32, Cx36, Cx43, Cx45 and Cx46 were all expressed. At the protein
      level, only Cx43 and Cx46 were detected. Expression of both isoforms was higher
      in LE-RPE as compared to RCS-RPE by a factor of 1.25 and 2 respectively.
      Phosphorylation of Cx43 was increased upon activation of protein kinase C (PKC)
      by 1 microM phorbol 12-myristate 13-acetate (PMA). The phosphorylation status was
      not changed in hyperglycemic conditions, but this treatment strongly decreased
      total Cx43 levels to about 75 and 40% (in LE-RPE and RCS-RPE cells respectively)
      of the control level in LE-RPE cells. This decrease could be overcome by PKC
      downregulation. These results demonstrate that PKC activation and hyperglycemic
      conditions have different effects on Cx43 and that PKC is involved in the
      metabolic pathway induced by hyperglycemic conditions.

PMID- 11331936
TI  - Photomodification of the electrical properties of the plasma membrane: a
      comparison between 6 different membrane-active photosensitizers.
AB  - The present study deals with photomodification of the electrical properties of
      the plasma membrane of an epithelial cell line (opossum kidney (OK) cells). The
      effect of photofrin II (previously investigated) is compared with that of 5 other
      membrane-active sensitizers: sulfonated Zn-phthalocyanine, merocyanine 540, rose
      bengal, methylene blue and protoporphyrin IX (an endogenous sensitizer induced by
      addition of its biosynthetic precursor 5-aminolaevulinic acid). The study was
      performed in order to investigate whether photomodification of the ion transport
      properties of the plasma membrane by membrane-active sensitizers is a general and
      early event in cellular photosensitization. The changes in the electrical
      properties were monitored by application of the whole-cell and the inside-out
      configuration of the patch-clamp technique. Illumination in the presence of the
      compounds (apart from merocyanine 540) gave rise to similar changes of the
      electrical properties of the membrane: depolarization of the membrane potential,
      inactivation of a large-conductance, Ca2+-dependent K+-channel (maxi-KCa), and a
      strong increase of the leak conductance of the membrane. This similarity
      indicates the general character of the functional photomodifications by membrane
      active sensitizers previously reported for photofrin II.

PMID- 11331937
TI  - Insulin/FGF-binding ciliary membrane glycoprotein from Tetrahymena.
AB  - Triton X-100 extracted ciliary membrane protein from isolated cilia, prepared
      from the protozoon Tetrahymena thermophila, were fractionated by affinity
      chromatography on columns with covalently bound fibroblast growth factor (FGF),
      insulin, or concanavalin A (ConA), respectively. The eluted proteins were further
      analyzed by electrophoresis on sodium dodecyl sulfate polyacrylamide gels,
      isoelectric focusing, and by immunoblotting techniques using antibodies against
      the FGF receptor, platetelet derived growth factor (PDGF) receptor alpha-subunit,
      and insulin receptor beta-subunit. The particular antibodies were chosen because
      the peptides PDGF, FGF, insulin, and ConA are chemoattractants in this organism
      and corresponding binding (receptor) proteins could be expected to be identified.
      A 66 kDa protein fraction was eluted from the FGF-MiniLeak agarose, insulin
      MiniLeak agarose and ConA sepharose. This fraction responded in Western
      immunoblots to an antibody against the beta-subunit of the human insulin
      receptor, to an antibody against the PDGF receptor (PDGFR) and also to an
      antibody against the bovine FGF receptor (FGFR) that is known, in other systems,
      to inhibit FGF binding to its receptor. When analyzed by SDS-PAGE and stained
      with Coomassie blue the 66 kDa fraction appeared as a single component. However,
      in some experiments it appeared more heterogeneous when stained with silver
      indicating the presence of minor components that may be a procedural artifact or
      isoforms of the same glycoprotein. The 66 kDa protein(s) migrated in isoelectric
      focusing with a pI of 7.4. The results are discussed in terms of the possible
      role of the 66 kDa glycoprotein as a protein involved in peptide-mediated cell
      signalling.

PMID- 11331938
TI  - Conduction of monovalent and divalent cations in the slow vacuolar channel.
AB  - The conduction properties of individual physiologically important cations Na+,
      K+, Mg2+, and Ca2+ were determined in the slowly activating (SV) channel of sugar
      beet vacuoles. Current-voltage relationships of the open channel were measured on
      excised tonoplast patches in a continuous manner by applying a +/-140 mV ramp
      wave protocol. Applying KCl gradients of either direction across the patch we
      have determined that the relative Cl- to K+ permeability was < or =1%.
      Symmetrical increase of the concentration of tested cation caused an increase of
      the single channel conductance followed by saturation. Fitting of binding
      isotherms at zero voltage to the Michaelis-Menten equation resulted in values of
      maximal conductance of 300, 385, 18, and 13 pS, and of apparent dissociation
      constants of 64, 103, 0.04, and 0.08 mm for Na+, K+, Mg2+, and Ca2+,
      respectively. Deviations from the single-ion occupancy mechanism are documented,
      and alternative models of permeation are discussed. The magnitude of currents
      carried by divalent cations at low concentrations can be explained by an
      unrealistically wide (approximately 140 A) radius of the pore entrance. We
      propose instead a fixed negative charge in the pore vestibules, which
      concentrates the cations in their proximity. The conduction properties of the SV
      channel are compared with reported characteristics of voltage-dependent Ca2+
      permeable channels, and consequences for a possible reduction of postulated
      multiplicity of Ca2+ pathways across the tonoplast are drawn.

PMID- 11331939
TI  - Nonrandom segregation during meiosis: the unfairness of females.
AB  - Most geneticists assume that chromosome segregation during meiosis is Mendelian
      (i.e., each allele at each locus is represented equally in the gametes). The
      great majority of reports that discuss non-Mendelian transmission have focused on
      systems of gametic selection, such as the mouse t-haplotype and Segregation
      distorter in Drosophila, or on systems in which post-fertilization selection
      takes place. Because the segregation of chromosomes in such systems is Mendelian
      and unequal representation of alleles among offspring is achieved through gamete
      dysfunction or embryonic death, there is a common perception that true
      disturbances in the randomness of chromosome segregation are rare and of limited
      biological significance. In this review we summarize data on nonrandom
      segregation in a wide variety of genetic systems. Despite apparent differences
      between some systems, the basic requirements for nonrandom segregation can be
      deduced from their shared characteristics: i) asymmetrical meiotic division(s);
      ii) functional asymmetry of the meiotic spindle poles; and iii) functional
      heterozygosity at a locus that mediates attachment of a chromosome to the
      spindle. The frequency with which all three of these requirements are fulfilled
      in natural populations is unknown, but our analyses indicate that nonrandom
      segregation occurs with sufficient frequency during female meiosis, and in
      exceptional cases of male meiosis, that it has important biological, clinical,
      and evolutionary consequences.

PMID- 11331940
TI  - Physical mapping of mouse collagen genes on chromosome 10 by high-resolution
      FISH.
AB  - Fluorescence in situ hybridization (FISH) on mechanically stretched chromosomes
      (MSCs) and extended DNA fibers enables construction of high-resolution physical
      maps by accurate ordering and orienting genomic clones as well as by measuring
      physical lengths of gaps and overlaps between them. These high-resolution FISH
      targets have hitherto been used mainly in the study of the human genome. Here we
      have applied both MSCs and extended DNA fibers to the physical mapping of the
      mouse genome. At first, five mouse collagen genes were localized by metaphase
      FISH: Col10a1 to chromosomal bands 10B1-B3; Col13a1 to 10B4; and Col6a1, Col6a2,
      and Col18a1 to 10B5-C1. The mutual order of the genes, centromere--Col10a1-
      Col13a1--Col6a2--Col6a1--Col18a1--telomere, was determined by FISH on metaphase
      chromosomes, MSCs, and extended DNA fibers. To our knowledge, this is the first
      time mouse metaphase chromosomes have been stretched and used as targets for
      FISH. We also used MSCs to determine the transcriptional orientations, telomere-
      5'-->3'--centromere, of both Col13a1 and Col18a1. With fiber-FISH, Col18a1,
      Col6a1, and Col6a2 were shown to be in a head-to-tail configuration with
      respective intergenic distances of about 350 kb and 90 kb. Comparison of our
      physical mapping results with the homologous human data reveals both similarities
      and differences concerning the chromosomal distribution, order, transcriptional
      orientations, and intergenic distances of the collagen genes studied.

PMID- 11331941
TI  - Molecular cloning and characterization of a gene expressed in mouse developing
      tongue, mDscr5 gene, a homolog of human DSCR5 (Down syndrome Critical Region gene
      5).
AB  - For understanding the pathogenesis of Down syndrome (DS), it is important to
      identify and characterize the genes on Chromosome (Chr) 21, especially those in
      the Down syndrome critical region (DSCR) on Chr 21q22.2. Recently we have
      determined 33.5 Mb (more than 99%) of DNA sequence of Chr 21 and, from these
      sequence data, we identified a novel gene, DSCR5 (transcript = 0.8 kb), from DSCR
      by combination of computational gene prediction and cDNA screening. For
      functional analysis of DSCR5, we identified a mouse homolog of the DSCR5 cDNA,
      and termed it mDscr5 (transcript length = 0.8 kb). The gene was mapped to mouse
      Chr 16 C3-C4, the syntenic region of human Chr 21, and encodes an amino acid of
      132 residues with 90% identity to DSCR5. In situ hybridization showed that mDscr5
      is predominantly expressed in the developing tongue. To our best knowledge, no
      other gene in DSCR is reported to be expressed in tongue, so that DSCR5 may be
      the first candidate to elucidate the pathophysiology of tongue malformation
      observed in DS.

PMID- 11331943
TI  - Mapping a blood pressure quantitative trait locus to a 5.7-cM region in Dahl salt
      sensitive rats.
AB  - A region on rat Chromosome (Chr) 2 of the Dahl salt-sensitive rat (S) was shown
      previously to contain a quantitative trait locus (QTL) for blood pressure (BP).
      This was achieved first by linkage, followed by the use of congenic strains. A
      congenic strain, designated S.MNS-D2Mit6/Adh, contained a segment of Chr 2 from
      the Milan Normotensive (MNS) rat in the S genetic background. Since the region
      containing the QTL was roughly 80 cM in size, a further reduction was needed
      towards the positional or candidate gene cloning. Currently, two congenic
      substrains were made from the original strain S.MNS-D2Mit6/Adh. One of these two
      substrains showed a BP-lowering effect, whereas the other substrain did not.
      Deducing the segment not shared in the two substrains, the BP QTL has to be
      present in a chromosome region of roughly 5.7 cM between the marker D2Rat303 and
      the locus for the neutroendopeptidase gene (Nep). Nep is not included within the
      segment. This region does not seem to contain any candidate genes well known for
      the BP control. Thus, the final identification of the QTL will most likely lead
      to the discovery of a brand new gene for the BP regulation.

PMID- 11331942
TI  - Mouse eosinophil-associated ribonucleases: a unique subfamily expressed during
      hematopoiesis.
AB  - A unique family of ribonucleases was identified by exhaustive screening of
      genomic and cDNA libraries using a probe derived from a gene encoding a
      ribonuclease stored in the mouse eosinophil secondary granule. This family
      contains at least 13 genes, which encode ribonucleases, and two potential
      pseudogenes. The conserved sequence identity among these genes (approximately
      70%), as well as the isolation/purification of these ribonucleases from
      eosinophil secondary granules, has led us to conclude that these genes form a
      unique clade in the mouse that we have identified as the Ear (Eosinophil
      associated ribonuclease) gene family. Analyses of the nucleotide substitutions
      that have occurred among these ribonuclease genes reveal that duplication events
      within this family have been episodic, occurring within three unique periods
      during the past 18 x 10(6) years. Moreover, comparisons of non-synonymous (K(a))
      vs. synonymous (K(s)) rates of nucleotide substitution show that although these
      genes conserve residues necessary for RNase activity, selective evolutionary
      pressure(s) exist such that acquired amino acid changes appear to be
      advantageous. The selective advantage of these amino acid changes is currently
      unclear, but the occurrence of this phenomenon in both the mouse and the human
      highlights the importance of these changes for Ear and, therefore, eosinophil
      effector function(s).

PMID- 11331944
TI  - A high-resolution comparative RH map of porcine chromosome (SSC) 2.
AB  - A high-resolution comparative map was constructed for porcine Chromosome (SSC) 2,
      where a QTL for back fat thickness (BFT) is located. A radiation hybrid (RH) map
      containing 33 genes and 25 microsatellite markers was constructed for this
      chromosome with a 3000-rad porcine RH panel. In total, 16 genes from human
      Chromosome (HSA) 11p, HSA19p, and HSA5q were newly assigned to SSC2. One linkage
      group was observed at LOD 3.0, and five linkage groups at LOD 4.0. Comparison of
      the porcine RH map with homologous human gene orders identified four conserved
      segments between SSC2 and HSA11, HSA19, and HSA5. Concerning HSA11, a
      rearrangement of gene order is observed. The segment HSA11p15.4-q13 is inverted
      on SSC2 when compared with the distal tip of SSC2p, which is homologous to
      HSA11p15.5. The boundaries of the conserved segments between human and pig were
      defined more precisely. This high-resolution comparative map will be a valuable
      tool for further fine mapping of the QTL area.

PMID- 11331945
TI  - An integrated cytogenetic, radiation-hybrid, and comparative map of dog
      chromosome 5.
AB  - The development of a detailed genome map for the domestic dog (Canis familiaris,
      CFA) is a prerequisite for the continued use of this species as a model system
      for the study of inherited traits. We present an integrated cytogenetic,
      radiation-hybrid, and comparative map of dog Chromosome (Chr) 5 (CFA 5). The map
      comprises 14 gene markers, selected from loci previously mapped within the
      corresponding evolutionarily conserved chromosome segments (ECCS) of the human
      genome. Large-insert clones representing each marker were first isolated and
      mapped by fluorescence in situ hybridization (FISH) analysis to determine their
      subchromosomal localization on CFA 5. Thirteen gene markers were subsequently
      mapped by using a commercially available whole genome radiation hybrid (WG-RH)
      panel for the dog. Nine anonymous markers were also assigned to CFA 5 by both
      FISH and WG-RH analysis. The 22 markers formed six RH-linkage groups, spanning
      each of the four ECCS comprising this 99 megabase chromosome. All cytogenetic, WG
      RH, and comparative mapping data were in agreement and were combined to determine
      both the most likely locus order within each linkage group, and also the gross
      relative orientation of the corresponding ECCS. This study provides a resource
      for the transfer of information from the human transcript map to that of the dog,
      and extends existing data regarding the structural relationships between CFA 5
      and its evolutionary counterparts within the human genome.

PMID- 11331946
TI  - The PrP-like protein Doppel gene in sheep and cattle: cDNA sequence and
      expression.
AB  - cDNAs encoding the ovine and bovine prion protein-like protein Doppel (Dpl) have
      been cloned. Sequencing revealed cDNAs of 2.85 and 3.31 kb from ovine and bovine
      testicular tissue, in accordance with observations of single transcripts of 3.2
      and 3.6 kb on Northern blots. Sequence alignments showed a very high degree of
      identity between the sheep and cattle Dpl cDNAs, except for a 0.4-kb stretch in
      the bovine 3' untranslated region and the terminal 3' end of the sequences. The
      expression pattern of the Dpl gene (Prnd) in adult tissues from both species was
      compared by Northern blot and RT-PCR analyses. The Prnd gene was expressed
      strongly in testicular tissue, while low levels of expression were seen in other
      tissues. The open reading frame of the ovine and bovine sequences encodes a 178
      amino acid protein with 95% sequence identity between the two species. Predicted
      structural features are in close agreement with previous reports for mouse,
      human, and rat Dpl.

PMID- 11331947
TI  - Construction of a high-resolution RH map of the human 2q35 region on TNG panel
      and comparison with a physical map of the porcine homologous region 15q25.
AB  - This article describes the construction of a high-resolution radiation hybrid map
      of Hsap 2q35 by using the TNG RH panel generated by irradiation with 50,000 rads.
      We were able to build a framework map of 1300 cR(50,000) including 34 markers
      ordered with odds higher than 1000:1. The comprehensive map includes 77 loci and
      describes a region of 3 Mb around the SLC11A1 gene. Because of the very small
      size of the fragments retained and a reduced retention frequency, it was
      difficult to build a high-resolution multi-point map of this region by using the
      TNG RH panel. Nevertheless, this study confirmed the very high potential of this
      RH panel for constructing a human, high-resolution physical map (2.3
      kb/cR(50,000)). Moreover, human ESTs from Hsap 2q35 were hybridized with porcine
      BAC contigs to establish a porcine transcript map of the homologous region Sscr
      15q25 (greater than 2.5 Mb). We identified 17 new genes in this porcine
      chromosomal region. We were able to compare the location of 26 genes mapped in
      both species. The gene order was similar except for two possible minor
      discrepancies in the Desmin sub-region, suggesting the existence of a porcine
      micro-region between TNP1 and IL8RB with an unknown origin.

PMID- 11331948
TI  - Genomic clustering of tRNA-specific adenosine deaminase ADAT1 and two tRNA
      synthetases.
AB  - Human tRNA-specific adenosine deaminase (hADAT1) specifically converts A37 in the
      anticodon loop of human tRNA(Ala) to inosine via a hydrolytic deamination
      mechanism. The enzyme is related to a family of RNA editing enzymes (ADARs)
      specific for pre-mRNA, and it has been cloned based on its sequence homology to
      the catalytic domain of ADARs. In the present study we have analyzed the 5'
      flanking sequence of the murine ADAT1 gene, revealing that the first transcribed
      exon is located 1.1 kb downstream from the polyadenylation site of lysyl tRNA
      synthetase (KARS). The close proximity is conserved in the human genome with an
      intergenic distance of 5.5 kb. We determined the complete cDNA sequence as well
      as exon/intron organization of murine KARS. Significant sequence similarities
      between KARS and ADAT1 are apparent within their substrate interaction domains.
      Radiation hybrid panel analysis mapped human ADAT1 and human KARS to region q22.2
      -22.3 of Chromosome (Chr) 16 with alanyl tRNA synthetase (AARS) positioned
      centromeric to the KARS and ADAT1 genes. 16q22--24 has recently been recognized
      as a susceptibility candidate locus for several autoimmune inflammatory diseases.
      The clustering of three tRNA specific genes, of which two are specific for
      tRNA(Ala), may indicate their evolutionary relatedness or common factors involved
      in regulating their expression.

PMID- 11331949
TI  - A class I MHC locus compared among felid species.

PMID- 11331951
TI  - Barrett esophagus--more steps forward.

PMID- 11331950
TI  - Cytogenetic and radiation hybrid mapping reveals conserved synteny and gene order
      between human chromosome 21 and pig chromosome 13.

PMID- 11331952
TI  - Expression of the retinoblastoma-related gene Rb2/p130 is downregulated in
      atypical endometrial hyperplasia and adenocarcinoma.
AB  - The retinoblastoma-related gene Rb2/p130 encodes a protein that is a negative
      cell-cycle regulator normally expressed in a number of adult tissues. This
      protein shares many structural and functional features with the product of the
      retinoblastoma gene, one of the best-studied tumor-suppressor genes, and plays a
      fundamental role in growth control. The Rb2/p130 gene product associates with
      specific members of the E2F family and various cyclins, displaying a growth
      suppressive activity specific for the G(0)/G(1) phases. It has been reported that
      Rb2/p130 is involved in the pathogenesis and progression of lung cancer and
      mesothelioma. We previously demonstrated for the first time that reduced
      immunohistochemical expression of Rb2/p130 was a strong independent predictor of
      poor outcome in endometrial cancer. The aim of the present study was to evaluate
      Rb2/p130 expression in normal, hyperplastic, and neoplastic endometrial lesions
      to determine whether the protein plays a significant role in endometrial
      carcinogenesis. We evaluated Rb2/p130 expression by immunohistochemistry staining
      in 102 specimens chosen to represent a spectrum of endometrial changes, including
      proliferative endometrium (n = 18), secretory endometrium (n = 18), simple or
      complex hyperplasia without atypia (n = 18), atypical hyperplasia (n = 18), and
      invasive carcinoma (n = 30). We found that Rb2/p130 was highly expressed in
      proliferative endometrium and in hyperplasia without atypia, the mean percentage
      of stained nuclei being 66% and 60%, respectively, but was downregulated in
      secretory endometrium, atypical hyperplasia, and carcinoma, with mean scores of
      38%, 25%, and 22%, respectively. When categorized on a semiquantitative scale
      (negative v 1% to 50% v >50% positivity), endometrial cancer displayed
      significantly less staining than all other endometrial samples (P <.001). Poorly
      differentiated carcinomas (n = 9) showed a significantly lower immunoreactivity
      for Rb2/p130 than did well-differentiated carcinomas (n = 11; P =.005) and
      moderately differentiated carcinomas (n = 10; P =.03). In addition, atypical
      hyperplasia showed a significantly lower immunoreactivity than either
      proliferative endometrium (P =.003) or hyperplasia without atypia (P = 0.02). Our
      findings of a progressive decrease in Rb2/p130 expression from hyperplastic
      endometrium through atypical hyperplasia to poorly differentiated carcinomas
      suggest the involvement of this negative cell-cycle regulator in endometrial
      carcinogenesis. Furthermore, immunostaining for Rb2/p130 may prove diagnostically
      useful in the often difficult distinction between hyperplastic and atypical
      hyperplastic endometrium. HUM PATHOL 32:360-367.

PMID- 11331953
TI  - Reproducibility of the diagnosis of dysplasia in Barrett esophagus: a
      reaffirmation.
AB  - Morphologic assessment of dysplasia in Barrett esophagus, despite limitations,
      remains the basis of treatment. We rigorously tested modified 1988 criteria,
      assessing intraobserver and interobserver reproducibility. Participants submitted
      slides of Barrett mucosa negative (BE) and indefinite (IND) for dysplasia, with
      low-grade dysplasia (LGD) and high-grade dysplasia (HGD), and with carcinoma. Two
      hundred fifty slides were divided into 2 groups. The first 125 slides were
      reviewed, without knowledge of the prior diagnoses, on 2 occasions by 12
      gastrointestinal pathologists without prior discussion of criteria. Results were
      analyzed by kappa statistics, which correct for agreement by chance. A consensus
      meeting was then held, establishing, by group review of the index 125 slides, the
      criteria outlined herein. The second 125-slide set was then reviewed twice by
      each of the same 12 pathologists, and follow-up kappa statistics were calculated.
      When statistical analysis was performed using 2 broad diagnostic categories (BE,
      IND, and LG v HG and carcinoma), intraobserver agreement was near perfect both
      before and after the consensus meeting (mean kappa = 0.82 and 0.80).
      Interobserver agreement was substantial (kappa = 0.66) and improved after the
      consensus meeting (kappa = 0.70; P =.02). When statistical analysis was performed
      using 4 clinically relevant separations (BE; IND and LGD; HGD; carcinoma), mean
      intraobserver kappa improved from 0.64 to 0.68 (both substantial) after the
      consensus meeting, and mean interobserver kappa improved from 0.43 to 0.46 (both
      moderate agreement). When statistical analysis was performed using 4 diagnostic
      categories that required distinction between LGD and IND (BE; IND; LGD; HGD and
      carcinoma), the pre-consensus meeting mean intraobserver kappa was 0.60
      (substantial agreement), improving to 0.65 after the meeting (P <.05).
      Interobserver agreement was poorer, with premeeting and postmeeting mean values
      unchanged (kappa = 0.43 at both times). Interobserver agreement was substantial
      for HGD/carcinoma (kappa = 0.65), moderate to substantial for BE (kappa = 0.58),
      fair for LGD (kappa = 0.32), and slight for IND (kappa = 0.15). The intraobserver
      reproducibility for the diagnosis of dysplasia in BE was substantial.
      Interobserver reproducibility was substantial at the ends of the spectrum (BE and
      HG/carcinoma) but slight for IND. Both intraobserver and interobserver variation
      improved overall after the application of a modified grading system developed at
      a consensus conference but not in separation of BE, IND, and LGD. The criteria
      used by the group are presented. HUM PATHOL 32:368-978.

PMID- 11331954
TI  - Dysplasia as a predictive marker for invasive carcinoma in Barrett esophagus: a
      follow-up study based on 138 cases from a diagnostic variability study.
AB  - The objective of endoscopic surveillance in Barrett esophagus (BE) is to assess
      the risk of subsequent development of invasive carcinoma. Criteria for
      morphologic evaluation of dysplasia, the presumed precursor lesion, have been
      established, although there are surprisingly few data in the literature
      correlating biopsy diagnosis of dysplasia with outcome. We collected follow-up
      information on 138 patients with BE whose initial endoscopic biopsy specimens had
      been selected for submission in an interobserver variability study performed by
      12 pathologists with special interest in gastrointestinal pathology and reviewed
      blindly twice each by all the participants. Cases were scored as BE with no
      dysplasia, atypia indefinite for dysplasia (IND), low-grade dysplasia (LGD), high
      grade dysplasia (HGD), intramucosal carcinoma, and frankly invasive carcinoma,
      thus generating 24 scores on each biopsy specimen. Clinical follow-up was
      obtained and correlated with both the submitting diagnoses and majority
      diagnoses. Kaplan-Meier statistics were used to compare both the submitting and
      majority diagnoses with outcome using detection or documentation of invasive
      carcinoma as the endpoint. Using the submitting diagnoses, no invasive carcinomas
      were detected in 44 cases diagnosed as BE (median follow-up, 38.5 months).
      Carcinomas were detected in 4 of 22 (18%) cases submitted as IND (median
      progression-free survival of 62 months), in 4 of 25 (15%) cases of LGD (median
      progression-free survival of 60 months), in 20 of 33 cases of HGD (median
      progression-free survival, 8 months), and all 13 (100%) cases submitted as
      adenocarcinoma. Grade on initial biopsy correlated significantly with progression
      to invasive carcinoma (log-rank P =.0001). Majority diagnosis was achieved in 99
      of the cases. Using the majority diagnoses, no invasive carcinomas were found in
      50 cases of BE (median follow-up, 48 months), and carcinomas were detected in 1
      of 7 (14%) IND cases (80% progression-free survival at 2 months), 3 of 15 (20%)
      LGD (median progression-free survival, 60 months), 9 of 15 (60%) HGD (median
      progression-free survival, 7 months), and all 12 (100%) carcinoma. Initial
      grading again correlated significantly with progression to invasive carcinoma
      (log-rank P =.0001). However, there were 39 cases without a majority diagnosis.
      Among these, no carcinomas developed in 8 cases with an average score between BE
      and IND. Carcinomas were detected in 9 of 21 (43%) cases with an average score
      between IND and LGD, and 7 of 10 (70%) cases with an average score between LGD
      and HGD. There were ulcers in 8 of 39 cases (20%) of the "no-majority" group and
      in 13 of 99 (13%) of the majority cases. Of 21 total ulcerated cases, cancer was
      demonstrated in 15 (71%) of these on follow-up. These data support combining the
      IND and LGD categories for surveillance purposes. Cases without dysplasia may be
      followed up conservatively. The data obtained from submitted diagnoses as opposed
      to those from blind review suggest that knowledge of the clinical findings aids
      in diagnosis. The data also support the assertion that HGD is strongly associated
      with invasive carcinoma. Rebiopsy of ulcerated areas should be considered because
      they may harbor malignancy. Histologic grading of dysplasia using established
      criteria is a powerful prognosticator in BE. HUM PATHOL 32:379-388.

PMID- 11331955
TI  - High-grade prostatic intraepithelial neoplasia with adjacent small atypical
      glands on prostate biopsy.
AB  - With high-grade prostatic intraepithelial neoplasia with adjacent small atypical
      glands (PINATYP), the issue is whether the small glands represent budding or
      tangentially sectioned glands off of adjacent high-grade prostatic
      intraepithelial neoplasia (PIN) or invasive cancer next to high-grade PIN. The
      histology and significance of PINATYP on biopsy have not been described. Among
      574 cases of high-grade PIN lesions on needle biopsy, we identified 71 cases of
      PINATYP. Most cases were consultations, and 51 cases were available for
      histologic review. At least 1 follow-up prostate biopsy was performed in each of
      55 cases. Immunohistochemistry for high-molecular-weight cytokeratin (HMWCK) was
      performed on cases in which material was available. The average patient age at
      diagnosis was 65.5 years (range, 48 to 103 years). The initial digital rectal
      examination, transrectal ultrasound, serum prostate-specific antigen (PSA) level,
      PSA velocity, and family history of prostate cancer did not predict cancer on
      repeat biopsy. In 39% of cases, high-grade PIN had a predominantly flat pattern,
      and remaining cases showed a predominance of other patterns (tufting,
      micropapillary, cribriform). The average number of high-grade PIN glands and
      adjacent small atypical glands were 11.5 (1 to 60) and 5.3 (1 to 21),
      respectively. The farthest adjacent small atypical gland averaged 0.12 mm from
      the high-grade PIN (0.01 mm to 0.4 mm), as measured with an ocular micrometer.
      The following histologic features did not predict cancer on repeat biopsy: more
      than 1 core involved by the high-grade PIN; number of high-grade PIN glands;
      number of small atypical glands; distance of small atypical glands from the high
      grade PIN; size and percentage of nucleoli; marked nuclear pleomorphism; and
      mitoses. Overall, the risk of cancer on repeat biopsy was 46%. Two findings
      predicted a lower risk of cancer on repeat biopsy: younger age (62.2 years benign
      v 68.3 years cancer; P =.004) and predominantly flat high-grade PIN (P =.007). In
      our material, PINATYP appears to be a greater risk factor than high-grade PIN
      alone in predicting cancer on rebiopsy. Although age and predominant pattern of
      associated high-grade PIN may be helpful in predicting which men with this lesion
      will have cancer on rebiopsy, they cannot be used reliably; therefore, all men
      with PINATYP should undergo repeat biopsy. HUM PATHOL 32:389-395.

PMID- 11331956
TI  - Differential expression of the cell-adhesion molecule Nr-CAM in hyperplastic and
      neoplastic human pancreatic tissue.
AB  - Nr-CAM is a member of the immunoglobulin superfamily of neural cell-adhesion
      molecules initially thought to be expressed mainly in the brain. Here we show the
      presence of Nr-CAM protein in normal human pancreas and characterize its
      expression in hyperplastic and neoplastic human pancreatic tissue. Nr-CAM is
      expressed on the cell surface in normal pancreatic acini with enhanced staining
      at cell-cell junctions, and weak or no surface staining is seen on normal ductal
      cells. Nr-CAM expression is markedly up-regulated in intraductal hyperplasia.
      Expression was well maintained in well or moderately differentiated carcinoma but
      was reduced or absent from most poorly differentiated tumors. In addition, 4 of 4
      human pancreatic adenocarcinoma cell lines tested demonstrated little or no Nr
      CAM expression. This differential regulation of Nr-CAM expression suggests that
      it may be involved in the pathogenesis and invasive/metastatic behavior of
      pancreatic cancers. HUM PATHOL 32:396-400.

PMID- 11331957
TI  - Highly proliferative intratumoral fibroblasts and a high proliferative
      microvessel index are significant predictors of tumor metastasis in T3 ulcerative
      type colorectal cancer.
AB  - Fibroblast and endothelial cell mitotic figures are seen in some areas of
      colorectal cancers, and the purpose of this study was to investigate whether the
      proliferative activity of fibroblasts and endothelial cells plays an important
      role in tumor progression of T3 ulcerative-type colorectal cancer. The tumor area
      of 157 colorectal cancers was divided into marginal elevated area and central
      depressed area (CDA), and at half the depth of the depression the CDA was in turn
      divided into CDA upper area (CDAU) and CDA lower area (CDAL). The proliferative
      activity of the tumor cells, fibroblasts, and endothelial cells was assessed
      immunohistochemically by double CD31/MIB-1 (anti--Ki-67 antigen) staining. The
      proliferative microvessel index was estimated as the percentage of microvessels
      lined by MIB-1-positive endothelial cells relative to the total microvessel
      count. Proliferative activities of tumor cells showed significant associations
      with those of fibroblasts and the proliferative microvessel indices in all of the
      corresponding areas. Proliferative activities of fibroblasts also showed
      significant associations with proliferative microvessel indices in all of the
      corresponding areas. Colorectal cancers with nodal metastasis showed
      significantly higher proliferative activities of fibroblasts in the CDAU than
      those without nodal metastasis (P <.001). The high proliferative activities of
      fibroblasts and proliferative microvessel indices in the CDAU showed significant
      associations with short distant organ metastasis-free periods in colorectal
      cancers without nodal metastasis (P <.001 and P =.010, respectively) and those
      with nodal metastasis (P =.024 and P =.036, respectively). Multivariate analysis
      showed that the highly proliferative fibroblasts in the CDAU significantly
      increased hazard rates of distant organ metastasis of colorectal cancer patients
      with nodal metastasis (P =.018). Proliferative activities of fibroblasts and
      endothelial cells in the CDAU are useful parameters for predicting tumor
      metastasis in patients with T3 ulcerative-type colorectal cancer. HUM PATHOL
      32:401-409.

PMID- 11331958
TI  - Transcriptional activation of p21 by vitamin D(3) or vitamin K(2) leads to
      differentiation of p53-deficient MG-63 osteosarcoma cells.
AB  - p21 (WAF1/CIP1) is a downstream effector of p53 and mediates growth arrest by
      inhibiting the action of G(1) cyclin-dependent kinases. However, it has been
      reported that the p21 expression was triggered by multiple differentiation
      inducing agents by a p53-independent pathway. These agents induced expression of
      p21 by binding to specific DNA elements and modulating transcriptional
      initiation. We demonstrated that the gene encoding p21 was not only a vitamin
      D(3) target gene but also a vitamin K(2) target gene in the cells and that their
      differentiation was well related to the transcriptional activation of the p21
      gene. Transient overexpression of p21, using adenovirus-driven p21 expression
      plasmid, in MG-63 cells in the absence of vitamins D(3) and K(2) resulted in
      their differentiation. The transcriptional activation of p21 by vitamin D(3) or
      vitamin K(2) in p53-deficient osteosarcoma cells demonstrated the p53-independent
      role of p21 in human osseous differentiation. HUM PATHOL 32:410-416.

PMID- 11331959
TI  - Web-based tissue microarray image data analysis: initial validation testing
      through prostate cancer Gleason grading.
AB  - Tissue microarray technology promises to enhance tissue-based molecular research
      by allowing improved conservation of tissue resources and experimental reagents,
      improved internal experimental control, and increased sample numbers per
      experiment. Organized, well-validated collection and analysis of the voluminous
      image data produced by tissue microarray technology is critical to maximize its
      value. Web-based technology for visual analysis and searchable storage of
      microarray image data could provide optimal flexibility for research groups in
      meeting this goal, but this approach has not been examined scientifically. Toward
      this goal, a prostate tissue microarray block containing 432 tissue cores (0.6 mm
      diameter) was constructed. Moderately compressed (200 kb).jpg images of each
      tissue spot were acquired and were saved using a naming convention developed by
      the SPORE Prostate Tissue Microarray Collaborative Group. Four hundred three
      tissue array spot images were uploaded into a database developed for this study
      and were converted to.fpx format to decrease Internet transmission times for high
      resolution image data. In phase I of the image analysis portion of the study,
      testing and preliminary analysis of the Web technology was performed by 2
      pathologists (M.A.R. and G.S.B.). In phase II, 2 pathologists (J.I.E. and T.M.W.)
      with no previous exposure to this technology and no knowledge of the structure of
      the study were presented a set of 130 sequential tissue spot images via the Web
      on their office computers. In phase III, the same pathologists were presented a
      set of 193 images, including all 130 from phase II and 63 others, with image
      presentation order randomized. With each zoomable tissue spot image, each
      pathologist was presented with a nested set of questions regarding overall
      interpretability of the image, presence or absence of cancer, and predominant and
      second most frequent Gleason grade. In phases II and III of the study, 319 of 323
      (99%) image presentations using this Web technology were rated interpretable.
      Comparing the 2 pathologists' readings in phases II and III, Gleason grade
      determinations by each pathologist were identical in 179 of 221 (81%)
      determinations and were within 1 point of each other in 221 of 221 (100%)
      determinations, a performance rate similar to if not better than that previously
      reported for direct microscopic Gleason grading. Interobserver comparison of
      Gleason score determinations and intraobserver comparisons for Gleason grade and
      score also showed a pattern of uniformity similar to those reported in direct
      microscope-based Gleason grading studies. Interobserver (7.5%) and intraobserver
      (5% and 3%) variability in determining whether diagnosable cancer was present
      point out the existence of a "threshold effect" that has rarely been studied but
      may provide a basis for identification of features that are most amenable to
      improved diagnostic standardization. In summary, storage and analysis of tissue
      microarray spot images using Web-based technology is feasible and practical, and
      the quality of images obtained using the techniques described here appears
      adequate for most tissue-based pathology research applications. HUM PATHOL 32:417
      427.

PMID- 11331960
TI  - Involvement of 2p23 in pulmonary inflammatory pseudotumors.
AB  - Pulmonary inflammatory pseudotumors (IP) are rare mesenchymal proliferations that
      have a polymorphic histology and an unpredictable biologic behavior. The
      histologic spectrum of IP has led to uncertainty as to whether this tumor has a
      reactive or neoplastic pathogenesis. Reports of extrapulmonary IP have identified
      clonal chromosomal aberrations involving 2p23 in the region of the ALK gene.
      Using fluorescence in situ hybridization with a probe flanking the ALK gene at
      2p23 and immunostaining for the ALK gene product, we studied formalin-fixed,
      paraffin-embedded tissues of pulmonary IP and found a subset (33%) with 2p23
      aberrations. We suggest that chromosomal rearrangements and ALK immunostaining
      may be helpful in the diagnosis of a group of pulmonary IP and should be
      investigated as a potential tool for predicting their future biologic behavior.
      An association with anaplastic large-cell lymphoma was also observed. HUM PATHOL
      32:428-433.

PMID- 11331961
TI  - Primary and secondary prostatic adenocarcinoma of the urinary bladder.
AB  - Urinary bladder involvement by prostatic adenocarcinoma (PAC) is not well
      characterized in the literature. Fifteen consecutive cases of PAC diagnosed in
      the urinary bladder over a period of 10 years were reviewed. All bladder and
      prostate slides from each patient were evaluated. Eleven patients (group A) had
      synchronous PAC in the prostate. In these patients, bladder PAC occurred 2 to 11
      years after the initial diagnosis of PAC in the prostate and tended to have a
      higher Gleason score than the original prostatic PAC. Four cases of bladder PAC
      in group A had areas with features of urothelial carcinoma, with focal positive
      immunoreactivity for thrombomodulin in 2 cases. Two patients (group B) had
      undergone radical prostatectomy for PAC 15 years earlier. The lesions in the
      urinary bladder in both cases showed histopathologic features similar to those
      seen in the previous prostatic malignancies. Two patients (group C) had histories
      of previously resected urothelial carcinoma. Bladder PAC was diagnosed at routine
      follow-up, and repeated prostate biopsy up to 2 years after the diagnosis of
      bladder PAC showed no evidence of prostatic PAC. PAC in the urinary bladder may
      be either primary or secondary. Secondary PAC is usually associated with high
      grade and high-stage carcinoma in the prostate and may mimic transitional cell
      carcinoma. Primary bladder lesions may or may not be associated with a history of
      PAC in the prostate. The prognosis of patients with the primary carcinoma is
      favorable. HUM PATHOL 32:434-440.

PMID- 11331962
TI  - Role of cytologic criteria in the histologic diagnosis of Gleason grade 1
      prostatic adenocarcinoma.
AB  - Gleason grade 1 prostatic adenocarcinoma is defined by its gland architecture,
      which resembles that of benign prostate more than any other grade. It is
      characterized by closely spaced glands and expansile tumor border. Cytoplasm is
      clear to pale, superficially identical to benign nodular hyperplasia (BPH).
      However, there is recent evidence that prostatic "clear-cell carcinoma,"
      including grade 1, has cytoplasm whose composition is distinctively different
      from BPH, being filled with lipid rather than with the protein-rich granules that
      characterize benign secretory cells or the nongranular protein matrix of other
      prostate cancers. We reasoned that grade 1 cancer might also have additional
      distinctive cellular features; we tested this hypothesis by observations on 17
      grade 1 carcinoma foci found as components of transition zone clear-cell cancers.
      Unlike BPH secretory cells, cells of grade 1 cancer were uniformly large with
      even, straight borders laterally and luminally. Nuclei appeared sometimes benign
      but were fixed in a basal row dissimilar to the uneven distribution in BPH.
      Nuclear pyknotic foci, blue-tinged cytoplasm, and abundant dense luminal
      secretion were distinctively common. Immunostain for glutathione-S transferase
      was negative in grade 1 cancer but lightly positive in BPH secretory cells. These
      cytologic findings were proposed to be useful as diagnostic clues, especially in
      small-needle biopsy samples, in which architecture may be difficult to interpret.
      HUM PATHOL 32:441-446.

PMID- 11331963
TI  - Clinicopathologic and molecular analysis of high-grade dysplasia and early
      adenocarcinoma in short- versus long-segment Barrett esophagus.
AB  - Barrett esophagus, especially dysplastic Barrett mucosa, has been regarded as a
      preneoplastic lesion for esophageal adenocarcinoma. However, the etiology and
      pathogenesis of dysplasia and early adenocarcinoma in short- (SSBE) and long-
      (LSBE) segment Barrett esophagus have not been studied in detail. The aims of
      this study were to clarify clinicopathologic and genetic differences between high
      grade dysplasia (HGD) and early adenocarcinoma in SSBE versus LSBE. We analyzed
      the clinicopathologic features from 47 patients (19 SSBE [<3 cm] and 28 LSBE [>
      or =3 cm]) with esophagectomy for HGD/T1 adenocarcinoma. Allelic losses on
      chromosomes 3p (FIHT), 5q (APC), 9p (p16), and 17p (p53) were compared in 12 HGD
      and 9 T1 tumors from 19 cases of SSBE and in 23 HGD and 15 T1 tumors from 28
      cases of LSBE. Patients with SSBE were more likely to be smokers than were
      patients with LSBE (94.7% v 57.1%; P =.004). HGD or T1 tumors arising from SSBE
      were less likely to show adjoining nondysplastic Barrett mucosa than those from
      LSBE (73.6% v 100%; P =.02). LSBE more frequently showed a circumferential
      pattern of Barrett mucosa than did SSBE (96.4% v 47.3%; P =.0002). Chromosomal
      allelic losses on 3p, 5q, 9p, and 17p were detected in 19% (4 of 21), 43% (15 of
      35), 40% (14 of 35), and 48% (16 of 33) of HGD, respectively, and 26% (5 of 19),
      35% (8 of 23), 35% (8 of 23), and 57% (13 of 23) of T1 tumor, respectively. There
      were no significant differences in allelic loss of 3p, 5q, 9p, or 17p in HGD or
      T1 tumors from SSBE versus LSBE. These results suggest that both HGD and early
      adenocarcinoma in SSBE and LSBE may occur through similar genetic alterations,
      whereas there are some clinicopathologic differences between SSBE and LSBE. HUM
      PATHOL

PMID- 11331964
TI  - Nasopharyngeal angiofibroma.

PMID- 11331965
TI  - Pyriform cell differentiation in Podarcis sicula is accompanied by the appearance
      of surface glycoproteins bearing alpha-galNAc terminated chains.
AB  - The present histochemical and cytochemical study using a lectin panel (WGA, GSI
      A4, GSI-B4, PSA UEA-I, PNA, LCA, Con-A, DBA, MPA, BPA) has demonstrated that, in
      Podarcis sicula, the differentiation of small follicle cells into pyriform cells
      by means of intermediate cells is accompanied by the appearance of glycoproteins
      bearing alpha-GalNAc terminated O-linked side chains on the cell surface. The
      distribution of DBA- and MPA-binding sites over the follicular epithelium changed
      during the different stages of oocyte growth. DBA- and MPA-binding sites first
      appeared at the beginning of folliculogenesis within the zona pellucida (ZP) and
      on the surface of small cells, i.e., the stem cells of pyriform cells. Afterward,
      labeling was evident on the cell surfaces of intermediate cells and, later on,
      also of pyriform cells. On the other hand, no labeling was detected on the small
      cells located under the basal lamina, which, reportedly, do not differentiate
      into pyriform cells (Filosa et al. J. Embryol. Exp. Morphol., 1979; 15:297-316).
      Once pyriform cells were differentiated, the distribution of DBA- and MPA-binding
      sites over the follicular epithelium remained unchanged until intermediate and
      pyriform cells underwent apoptosis (Motta et al. J. Exp. Zool., 1996; 276:233
      241) and the follicular epithelium transformed into a monolayer composed of small
      follicle cells only (Filosa Mon. Zool. Ital., 1973; 7:151-165). During this stage
      of oocyte growth, DBA and MPA labeling gradually decreased to completely
      disappear in the follicular epithelium of vitellogenic follicles. It is
      noteworthy that the observed changes in the distribution of DBA- and MPA-binding
      sites represent the first evidence recognized by lectins of a gradual
      modification of surface glycoprotein distribution over the follicular epithelium
      in the ovarian follicles of nonmammalian vertebrates so far studied. Finally, the
      zona pellucida (ZP), characterized by the presence of GalNAc, GluNAc, Man, and
      Gal, was demonstrated to be first synthetized by the oocyte and later on by the
      follicle cells.

PMID- 11331966
TI  - Morphological analysis of endocytosis in efferent ductules of estrogen receptor
      alpha knockout male mouse.
AB  - Lack of estrogen receptor (ER) results in fluid accumulation and dilation of the
      efferent ductules, suggesting that the role of estrogen and ER in the male
      reproductive tract is related to fluid reabsorption in the ductules. In the
      present study, endocytosis of the nonciliated cells of the efferent ductules was
      compared morphologically between wild type (WT) and estrogen receptor-alpha
      knockout (alpha ERKO) male mice. The epithelial cells lining the WT efferent
      ductules were tall columnar in shape, whereas those of the alpha ERKO were low
      columnar. Immunocytochemically, the nonciliated cells of both genotypes showed
      positive reactions of sulfated glycoprotein-2, but the reaction products were
      reduced in amount in the alpha ERKO. Electron microscopy revealed that the
      nonciliated cells of the WT had numerous organelles for endocytosis such as
      coated pits and vesicles, tubules, endosomes, multivesicular bodies and lysosomes
      in the apical cytoplasm. These organelles were less developed in the nonciliated
      cells of the alpha ERKO. Morphometric analysis indicated that there was a
      significant reduction in area of endocytotic apparatus in the nonciliated cells
      of the alpha ERKO compared with that of the WT. A tracer study using gold
      particles demonstrated that the nonciliated cells of both WT and alpha ERKO
      efferent ductules were capable of taking up luminal contents. These results
      suggest that reabsorption of the luminal contents via endocytosis takes place in
      the efferent ductules but is greatly reduced in amount in the absence of ER
      alpha.

PMID- 11331967
TI  - Testosterone mediates satellite cell activation in denervated rat levator ani
      muscle.
AB  - Denervation stimulates quiescent satellite cells in skeletal muscle to reenter
      the cell cycle. In the androgen-sensitive rat levator ani muscle (LA), this
      mitotic response to loss of neural input fails to occur in castrated animals. To
      elucidate the role of androgens in denervation-induced satellite cell
      proliferation, the denervated LA of castrated rats (Group A) was compared with
      that of animals infixed with testosterone implants after castration (Group B).
      Mean myofiber cross-sectional areas (Group A: 362.95 microm(2) +/- 27.74; Group
      B: 403.13 microm(2) +/- 53.87) and linear nuclear densities (Group A: 74.07 mm(
      1) +/- 17.58; Group B: 104.13 mm(-1) +/- 4.06) were similar (P > 0.05) in both
      groups. The androgen-deprived myofibers of Group A, however, had a significantly
      lower nuclear content (271.0 +/- 74.91 vs. 1,285.80 +/- 81.74 in Group B; P <
      0.05) on account of their considerably shorter mean length (3.44 mm +/- 0.29 vs.
      12.31 mm +/- 0.92 in Group B; P < 0.05). The proportional representation of
      satellite cells in hormone-replaced, denervated muscle was more than twice that
      in the untreated group (Group B: 5.15 +/- 0.83% vs. Group A: 2.28 +/- 0.23%; P <
      0.05). In absolute terms, the satellite cell number in Group B was approximately
      an order of magnitude greater than in Group A (408.4 x 10(3) vs. 38.08 x 10(3)).
      The results confirm the absence of testosterone as the factor responsible for the
      inability of satellite cells in the LA of castrated rats to respond mitotically
      to the withdrawal of neural input after denervation.

PMID- 11331968
TI  - Functional overexpression of wild-type p53 correlates with alveolar cell
      differentiation in the developing human lung.
AB  - At 15 weeks after conception (a.c.), the human pulmonary acinus is lined by
      distal low-columnar and more proximal cuboidal cells that are successive stages
      in alveolar type II cell differentiation (pseudoglandular period of lung
      development). From 16 weeks a.c. onward, there are also 'flatter' cells that are
      intermediate stages in the differentiation of cuboidal type II cells into
      squamous type I cells (canalicular period). We investigated the role of wild-type
      p53 protein and the proliferation marker Ki-67 in the differentiation of type II
      and type I cells in these two periods. Serial sections from fetal lungs (n = 30)
      were immunoincubated with antibodies against p53 and Ki-67. The presence of
      prospective type II and type I cells was confirmed using immunohistochemistry for
      surfactant protein SP-A as a differentiation marker and light and electron
      microscopy. The p53 and Ki-67 positive nuclei were quantified per alveolar cell
      phenotype (i.e., low-columnar; cuboidal; flatter). The occurrence of cell
      apoptosis was studied using propidium iodide (PI) and 4',6'-diamino-2-phenylindol
      dihydrochloride (DAPI) staining. The combined increase in p53 expression and
      decrease in Ki-67 expression during alveolar epithelial cell differentiation
      suggests that wild-type p53 protein plays a role in the differentiation of
      alveolar type II and type I cells in the human lung, and that this function is
      mediated through cell cycle arrest. The rare incidence of apoptotic nuclei in
      alveolar type II cells, together with their absence in alveolar type I cells,
      supports the view that p53 is involved in the differentiation, rather than the
      death, of alveolar epithelial cells.

PMID- 11331969
TI  - Topography of corpuscular mechanoreceptors in the shoulder joint region of
      monodelphis domestica.
AB  - The topography and structure of corpuscular mechanoreceptors in the shoulder
      joint capsule and periarticular connective tissue of a small laboratory marsupial
      (monodelphis domestica) were studied using light and electron microscopy. This
      animal is known to use its upper extremities for a wide range of activities like
      climbing and manipulating food. Thus, the shoulder joint of this animal species
      has a similar wide range of movement as the human shoulder joint, but is small
      enough for serial sectioning in its entirety. Silver stained serial paraffin
      sections were examined under the light microscope and the distribution of the
      different types of mechanoreceptors was reconstructed using three-dimensional
      image processing. In addition, selected mechanoreceptors were studied electron
      microscopically. Approximately 100 small lamellated corpuscles were found in the
      dense connective tissue of the joint capsule close to the insertion on the
      scapula and in the thickening of the joint capsule close to the glenoid labrum.
      Ruffini corpuscles were found in much smaller numbers in the moderately dense
      connective tissue of the axillary region. Only very few Vater-Pacinian corpuscles
      were seen in the soft periarticular connective tissue. The large number and
      localization of mechanoreceptor corpuscles in the shoulder joint capsule
      especially close to the glenoid labrum suggests, that these specialized nerve
      endings are likely to play an important role in control of joint movement. They
      can induce protective reflexes during extreme movements in the shoulder joint
      preventing shoulder luxation by increasing the tone of muscles pressing the
      humerus head into the glenoid cavity.

PMID- 11331970
TI  - Anatomical study of the obturator internus, gemelli and quadratus femoris muscles
      with special reference to their innervation.
AB  - The manner of innervation of the obturator internus, superior and inferior
      gemelli, and the quadratus femoris in humans (101 pelvic halves) and in rhesus
      monkeys (Macaca mulatta: 8 pelvic halves) were investigated. In most specimens,
      the inferior gemellus originated from the lateral surface of the ischial
      tuberosity and also from the medial surface (intrapelvic origin) just beneath the
      obturator internus and was covered by the falciform process of the sacrotuberous
      ligament. The superior gemellus was frequently innervated by the nerve to the
      obturator internus and the nerve to the quadratus femoris (60.4%), and the
      inferior gemellus was innervated by the obturator internus nerve in two
      specimens. The quadratus femoris nerve originated from more cranial segments than
      the obturator internus nerve, however these nerves had various communication
      patterns inside and outside the muscles. According to the intramuscular nerve
      distribution, in some specimens the branches to the superior gemellus from the
      quadratus femoris nerve extended to the inferior gemellus, and the branches to
      the inferior gemellus were distributed to the obturator internus. The present
      findings revealed that the positional relationships among the branches to the
      obturator internus and gemelli muscles are relatively constant, although the
      branching patterns and innervation patterns were varied. The various patterns and
      routes are considered to reflect the variability of the differentiation patterns
      of the anlage of the muscles. A possible schematic model of the positional
      relationships between the muscles and the nerves is proposed.

PMID- 11331971
TI  - Retinoic acid administration is associated with changes in the extracellular
      matrix and cardiac mesenchyme within the endocardial cushion.
AB  - Retinoic acid has been associated with a number of cardiac defects, some of which
      seem to be related to changes in the endocardial cushions. Studies in mice and
      older chick embryos have suggested that these defects may be associated with a
      decrease in mesenchymal cell formation within the cushion. In a previous report
      we showed that retinoic acid lowered the number of mesenchymal cells in a culture
      bioassay of mesenchyme formation and that this response was due to retinoic acid
      modifying the production of particulate matrix from the myocardium. In this
      study, we have extended these observations to the embryo by implanting a retinoic
      acid coated bead into the embryo and examined the effect on cardiac mesenchyme
      formation and in the production of the particulate matrix. In all cases the
      addition of retinoic acid resulted in a decrease in the number of mesenchymal
      cells invading the endocardial cushions. In addition retinoic acid increased the
      production of hLAMP-1 and fibronectin but not transferrin, confirming our earlier
      report. Finally, we measured the volume of the cushion and calculated the cell
      density of both the inferior and superior cushions. The results suggest that the
      superior cushion is more sensitive to retinoic acid treatment than the inferior
      cushion. Collectively, these results support our earlier work that suggests that
      the mechanism of retinoic acid cardiac abnormalities involves a disruption in the
      production of particulate matrix from the myocardium and a subsequent decrease in
      cardiac mesenchyme cells that results in a malformed cardiac cushions.

PMID- 11331972
TI  - Cardiopulmonary malformations in the inv/inv mouse.
AB  - The inv/inv mouse carries an insertional mutation in the inversin gene, (inv, for
      inversion of embryonic turning). Previously it had been reported that almost 100%
      of the homozygous offspring (inv/inv) were characterized by situs inversus
      totalis. In this report we identify the spectrum of cardiopulmonary anatomical
      abnormalities in inv/inv mice surviving to birth to determine whether the
      abnormalities seen are of the categories classically associated with human situs
      abnormalities. Stillborn mice, offspring that died unexpectedly (within 48 hr
      after birth), and neonates with phenotypic characteristics of situs inversus
      (right-sided stomachs, growth failure or jaundice) were processed for standard
      histological examination. Of 173 offspring, 34 (20%) neonates (11 stillborn, 9
      unexpected deaths, and 14 mice with situs inversus phenotype) were examined, 27
      of which were genotyped to be inv/inv. Interestingly, three inv/inv mice (11%)
      were found to have situs solitus. Twenty-four had situs inversus with normal,
      mirror-image cardiac anatomy (dextrocardia with atrioventricular concordance,
      ventriculoarterial concordance and a right aortic arch). The overall incidence of
      cardiovascular anomalies observed was 10 out of 27 (37%). The most frequent
      severe malformation, identified in 3 out of 27 animals, was a complex consisting
      of pulmonary infundibular stenosis/atresia with absence of pulmonary valve tissue
      and a ventricular septal defect. The pulmonary phenotype in inv/inv mice was
      situs inversus with occasional minor lobar abnormalities. We conclude that 1)
      cardiopulmonary malformations in inv/inv mice are not rare (37%), 2) the
      cardiopulmonary malformations observed in inv/inv specimens are not of the
      spectrum typically associated with human heterotaxia. In particular, inv/inv mice
      have a propensity for defects in the development of the right ventricular outflow
      tract and the interventricular septum, and 3) approximately one out of ten
      inv/inv mice is born with situs solitus and shows cardiac anomalies that
      correspond to those observed in inv/inv specimens with situs inversus. Our data
      therefore suggest that inversin, the product of the inv locus, may have specific
      roles in cardiac morphogenesis independent of its role in situs determination.

PMID- 11331973
TI  - Comparative studies on the expression patterns of three troponin T genes during
      mouse development.
AB  - In vertebrates, three troponin T (TnT) genes, cardiac TnT (cTnT), skeletal muscle
      fast-twitch TnT (fTnT), and slow-twitch TnT (sTnT), have evolved for the
      regulation of striated muscle contraction. To understand the mechanism for muscle
      fiber-specific expression of the TnT genes, we compared their expression patterns
      during mouse development. Our data revealed that the TnT expression in the
      developing embryo was not as restricted as that in the adult. In addition to a
      strong expression in the developing heart beginning at day 7.5 p.c (postcoitum),
      the cTnT transcript was detected at later stages in some skeletal muscles, where
      beginning at day 11.75 p.c. the fTnT and sTnT genes were also expressed. Only
      sTnT but not fTnT was found transiently in the developing heart. At day 13.5
      p.c., expressions of all three genes were detected in the developing tongue and
      this co-expression continued to day 16.5 p.c. with the fTnT isoform being
      predominant. At this stage, overlapping and distinct expression patterns of both
      sTnT and fTnT genes were also evident in many developing skeletal muscles. These
      data suggest that different muscles during development undergo a complex change
      in TnT isoforms resulting in different contractile properties. Unexpectedly, the
      cTnT transcript was persistently found in the developing bladder, where
      presumably smooth muscle is present. In transgenic mice, expression of a LacZ
      gene driven by a rat cTnT promoter (-497 to +192 bp) was very similar to that of
      the endogenous cTnT gene, suggesting that this promoter contained regulatory
      elements sufficient for the control of tissue-specific cTnT expression during
      development.

PMID- 11331974
TI  - Garlic prevents ultrastructural alterations caused by dehydration in mouse
      cerebral microvessels.
AB  - Dehydration is known to significantly reduce both the time required for the first
      platelet aggregate and the time to full occlusion in photochemically-induced
      thrombosis, in vivo. Ultrastructural changes that contribute to such events
      remain unknown. Therefore, the effect of water deprivation for 24 hr, (as a model
      for dehydration) on the ultrastructure of mouse pial microvessels was
      investigated. The possible beneficial effect of garlic in preventing such
      ultrastructural changes was also investigated. Four groups of TO strain: control,
      control-garlic treated, dehydrated, and dehydrated-garlic treated male mice,
      10/group, were used. Dehydration was induced by water deprivation for 24 hr.
      Garlic solution was i.p. injected at 0.1 ml/10g body weight. In urethane
      anesthetized (2 mg/g, i.p.) mice, topical and transvessel bimodal fixation of
      pial microvessels was done with a phosphate buffered mixture of glutaraldehyde
      and paraformaldehyde, followed by a conventional electron microscopy procedure.
      Examination of control cerebral pial microvessels showed no evidence of cellular
      damage. Membranes of endothelial cells were intact. Within pial microvessels
      there was no evidence of platelet aggregation. Garlic treatments did not cause
      any ultrastructure abnormalities in control mice. Compared with control,
      dehydration caused the appearance of thrombi that consisted of platelet
      aggregates. Discoid platelets containing granules, spheroid degranulated
      platelets, and those with large pseudopodia were present in 80% of dehydrated
      mice. The venular endothelial surface of dehydrated mice revealed dilated
      profiles of endoplasmic reticulum and variously shaped vacuoles. Swelling of
      nuclear envelopes and mitochondrial distension were also present in dehydrated
      mice. Concomitant garlic treatment prevented most of these ultrastructural
      changes. These findings demonstrated the extent of damage to the pial
      microvessels in response to water deprivation and demonstrated the beneficial
      effect of garlic as a possible mean of protection against oncoming vascular
      pathology.

PMID- 11331975
TI  - Differential expression of multiple genes during articular chondrocyte
      redifferentiation.
AB  - Articular chondrocytes undergo a rapid change in phenotype and gene expression,
      termed dedifferentiation, when isolated from cartilage tissue and cultured on
      tissue culture plastic. On the other hand, "redifferentiation" of articular
      chondrocytes in suspension culture is characterized by decreased cellular
      proliferation and the reinitiation of synthesis of hyaline articular cartilage
      extracellular matrix molecules. The molecular triggers for these events have yet
      to be defined. Subtracted cDNA libraries representing genes involved in the early
      events of adult human articular chondrocyte redifferentiation were generated from
      human articular chondrocytes that were first cultured in monolayer, and
      subsequently transferred to suspension culture at 10(6) cells/ml for
      redifferentiation. Differential regulation of genes involved in cellular
      organization, nuclear structure, cellular growth regulation, and extracellular
      matrix deposition and remodeling were observed within 48 hr of this transfer.
      Many of these genes had not been previously identified in the chondrocyte
      differentiation pathway and a number of the isolated cDNAs did not have
      homologies to sequences in the public data banks. Genes involved in IL-6 signal
      transduction including acute phase response factor (APRF), Mn superoxide
      dismutase, and IL-6 itself were up-regulated in suspension culture. Membrane
      glycoprotein gp130, a component of the IL-6 receptor, was down-regulated. Other
      genes involved in cell polarity, cell adherence, apoptosis, and possibly TGF-beta
      signaling were differentially regulated. The differential regulation of the
      cytokine connective tissue growth factor (CTGF) during the early stages of
      articular chondrocyte redifferentiation, decreasing within 48 hours of transfer
      to suspension culture, was particularly interesting given its reported role in
      the stimulation of cellular proliferation. CTGF was highly expressed in
      proliferative monolayer culture, and then greatly reduced by redifferentiation in
      standard high-density suspension culture. When articular chondrocytes were seeded
      in suspension at low-density (10(4) cells/ml), however, high levels of CTGF were
      observed along with increased levels of mature articular cartilage extracellular
      matrix protein RNAs, such as type II collagen and aggrecan. Although the role of
      CTGF in articular cartilage biology remains to be elucidated, the results
      described here demonstrate the potential utility of subtractive hybridization in
      understanding the process of articular chondrocyte redifferentiation.

PMID- 11331976
TI  - Intracranial distribution of the sympathetic system in mice: DiI tracing and
      immunocytochemical labeling.
AB  - The intracranial distribution of the cephalic branches of the superior cervical
      ganglion (scg) was studied in mice using indocarbocyanine dye (DiI) anterograde
      tracing. Two main branches were traced from the scg. The first branch joined the
      nerve of the pterygoid canal (the vidian nerve), npc, from which several
      intracranial sympathetic branches passed to the branches of the trigeminal nerve
      (tgn), abducent nerve (abn), trochlear nerve (trn), and oculomotor nerve (ocn).
      Most of the second branch joined the abn, from which sympathetic fibers dispersed
      in the distal region of the trigeminal ganglion (tgg) to form a plexus close to
      the ganglion's branches. Branches from this plexus joined the branches of the
      tgn, trn, and ocn. Several minor branches arising from the second branch of the
      scg were also observed. One formed a sympathetic plexus around the internal
      carotid artery (ica); a second formed a sympathetic plexus in the proximal region
      of tgg, close to its root; and a third branch coursed laterally to reach the ear
      by passing along the greater petrosal nerve (gpn). All of the intracranial
      trajectories traced from scg were found to be catecholaminergic, and likely
      sympathetic, using tyrosine hydroxylase (TH) immunocytochemistry.

PMID- 11331977
TI  - Billing Medicare for diabetes self-management training.

PMID- 11331978
TI  - Worth while Web: 50 useful sites for family physicians.

PMID- 11331979
TI  - Identifying the causes of staff turnover.

PMID- 11331980
TI  - Seven tips for effecting legislative change.

PMID- 11331981
TI  - Tailoring new physicians to fit your practice.

PMID- 11331982
TI  - Focus on the family, Part II: Does a family focus affect patient outcomes?

PMID- 11331983
TI  - Limiting restrictive covenants.

PMID- 11331984
TI  - Five priority-setting traps.

PMID- 11331985
TI  - Design guidelines for push-pull ventilation systems through computational fluid
      dynamics modeling.
AB  - Open surface tanks often are used in industrial practice. When harmful substances
      are involved, control of worker exposure requires the use of a local ventilation
      system. The push-pull system, among others, involves a jet of air that is blown
      from one side of the tank and collected by an exhaust hood on the opposite side;
      this system can save up to 50% of the ventilation air. Several guidelines are
      available for design of such a ventilation system, mainly based on experimental
      results. However, their validity is confined inside a narrow operating window. In
      this work a mathematical model developed based on computational fluid dynamics
      has been used to extend the validity of the existing guidelines outside the range
      in which they have been validated, with particular reference to tank width and to
      the velocity of the air drafts.

PMID- 11331986
TI  - Modeling turbulent diffusion and advection of indoor air contaminants by Markov
      chains.
AB  - Turbulent eddy diffusion models are used to describe a continuous concentration
      gradient with distance from an in-room contaminant emission source. A refined
      diffusion model termed the Drivas model also accounts for contaminant reflection
      by wall surfaces and partially accounts for removal by exhaust air. This article
      develops two models based on Markov chains to describe indoor air contaminant
      dispersion by turbulent diffusion and advection, and removal by the exhaust
      airflow. Markov model I is equivalent to the Drivas model and is computationally
      simple. Markov model II can provide more realism by accounting for the locations
      of air inlets and outlets, advective flow patterns, in-room reflective surfaces,
      and contaminant removal mechanisms at specific room positions. The price paid for
      this greater realism is greater computational complexity. Both Markov models are
      explicitly probabilistic and estimate the expected concentration values at given
      room positions.

PMID- 11331987
TI  - Effect of in situ composting on reducing offensive odors and volatile organic
      compounds in swineries.
AB  - Seven swine farms were studied to find out how the in situ composting system,
      compared to the slatted floor pit system, influences the concentration and
      occurrence of malodorous compounds. Ammonia concentrations were measured with
      diffusion tubes. Small molecular sulfur compounds were analyzed using laminated
      bags and a gas chromatograph with a FP-detector. All other volatile organic
      compounds were analyzed by gas chromatography/mass spectrometry with simultaneous
      sniffing of the eluted compounds. About 400 organic compounds were identified
      from the air samples, and 94 suspect odorous compounds are listed in the present
      article. The most intense and unpleasant odors were caused by p-cresol,
      carboxylic acids (C2-C7), and some ketones such as 3-hydroxy-2-butanone, 2,3
      butanedione, and 2-butanone. Terpenes (alpha-pinene, beta-pinene, 3-carene, and
      limonene), which originate from sawdust, caused the main peaks in the
      chromatograms of compost swineries. In swine confinement buildings where the
      composting system was functioning properly, the concentration of sulfur
      compounds, and especially of carboxylic acids, ketones, and p-cresol, fell
      effectively. The use of sawdust as composting material caused elevated
      concentrations of terpenes in the ambient air. There was clearly less airborne
      ammonia and hydrogen sulfide in the well-functioning compost swineries than in
      the poorly functioning ones. Elevated hydrogen sulfide levels were measured
      during turning work, however. In one composting swinery, the hydrogen sulfide
      level was as high as 15 mg/m3 during turning work. All the other concentrations
      of odorous compounds did not exceed occupational exposure limit values, but
      several compounds exceeded the respective threshold odor concentrations.

PMID- 11331988
TI  - A simple method for detecting breakthroughs in used chemical cartridges.
AB  - This study was intended to develop a simple method using a gas detector tube to
      detect the end of the service lives of chemical cartridges for organic solvent
      vapors. The practical usefulness of this method was confirmed by two series of
      experimental observations of cartridge service lives: (1) The breakthrough times
      for six organic solvents were determined by passing a test airflow through a
      cartridge, and the concentration at each breakthrough was measured with a gas
      chromatograph (GC). These GC-obtained concentrations were compared with the
      migrated vapor concentrations through each broken cartridge measured with a gas
      detector tube. (2) CS2 breakthrough of the cartridges used on 32 viscose rayon
      workers were measured with detector tubes, after which the residual service life
      of each cartridge was determined. In laboratory experiments the released
      concentrations detected by the gas detector tube were approximately equal to the
      final leak concentrations measured by GC. In a field survey the used cartridges
      exhibiting a stain of CS2 from detector tubes for concentrations greater than 4
      ppm were found not to have enough residual adsorption capacity for CS2. Migrated
      concentrations of CS2 measured with detector tubes were found to be a reasonable
      predictor of remaining service life.

PMID- 11331989
TI  - Characterization and control of terpene emissions in Finnish sawmills.
AB  - This article describes an experimental study of terpene emission rates during
      fresh pine and spruce sawing and processing. Total terpene emission was
      determined by summing the product of the exhaust airflow rate and the mean
      concentration in the exhaust. Terpene concentrations were measured at fixed
      sampling points between the sawing lines. Terpene emission during pine sawing was
      found to be around 10 times greater than that during spruce sawing. The emission
      rates given here can be used to predict emission rates for various production
      rates. The predicted emission rates can be used in mass balance models to predict
      concentrations or required airflow rates to achieve the target concentration
      level.

PMID- 11331990
TI  - Benzene and total hydrocarbons exposures in the downstream petroleum industries.
AB  - A review of studies, including both articles published in peer-reviewed journals
      and reports that were not peer reviewed, regarding occupational exposure to
      benzene and total hydrocarbons in the downstream petroleum industry operations
      was performed. The objective was to provide a broad estimate of exposures by
      compiling exposure data according to the following categories: refinery,
      pipeline, marine, rail, bulk terminals and trucks, service stations, underground
      storage tanks, tank cleaning, and site remediations. The data in each category
      was divided into personal occupational long-term and short-term samples. The
      summarized data offers valuable assistance to hygienists by providing them with
      an estimate and range of exposures. The traditional 8-hour time-weighted average
      (TWA) exposure and the 40-hour workweek do not generally coincide with exposure
      periods applicable to workers in marine, pipeline, railcar, and trucking
      operations. They are more comparable with short-term exposure or task-based
      exposure assessments. The marine sector has a large number of high exposures.
      Although relatively few workers are exposed, their exposures to benzene and total
      hydrocarbons are sometimes an order of magnitude higher than the respective
      exposure limits. It is recommended that in the future, it would be preferable to
      do more task-based exposure assessments and fewer traditional TWA long-term
      exposure assessments within the various sectors of the downstream petroleum
      industry.

PMID- 11331991
TI  - Exposure estimation in the presence of nondetectable values: another look.
AB  - A common problem faced by industrial hygienists is the selection of a valid way
      of dealing with those samples reported to contain nondetectable values of the
      contaminant. In 1990, Hornung and Reed compared a maximum likelihood estimation
      (MLE) statistical method and two methods involving the limit of detection, L. The
      MLE method was shown to produce unbiased estimates of both the mean and standard
      deviation under a variety of conditions. That method, however, was complicated,
      requiring difficult mathematical calculations. Two simpler alternatives involved
      the substitution of L/2 or L/square root of 2 for each nondetectable value. The
      L/square root of 2 method was recommended when the data were not highly skewed.
      Although the MLE method produces the best estimates of the mean and standard
      deviation of an industrial hygiene data set containing values below the detection
      limit, it was not practical to recommend this method in 1990. However, with
      advances in desktop computing in the past decade the MLE method is now easily
      implemented in commonly available spreadsheet software. This article demonstrates
      how this method may be implemented using spreadsheet software.

PMID- 11331992
TI  - The capture envelope of a flanged circular hood in cross drafts.
AB  - The flow patterns of an exterior circular hood subject to the influence of
      various uniform cross drafts were experimentally studied in an apparatus
      consisting of hood-model/wind-tunnel assembly. A two-component laser Doppler
      anemometer was employed to measure the velocity field on the symmetry plane. The
      streamline patterns were obtained from the measured velocity data. The cross
      draft caused a characteristic envelope similar to a half Rankine body-of
      revolution to form in the flow field. The boundary of the envelope is described
      by a dividing streamline. All streamlines within the envelope lead to the
      opening; those outside the envelope evolve to the downstream area. The normalized
      geometry of the capture envelope is theoretically justified and correlated by
      modifying the potential theory of point-sink-plus-rectilinear-flow. The domain
      and shape of the envelope enclosing the hood opening are determined primarily by
      the velocity ratio between the cross draft and hood suction. The correlated
      formula is applicable to design the hood parameters, including the sizes of
      opening and flange as well as the location of contaminant sources.

PMID- 11331993
TI  - The history of OSHA's asbestos rule makings and some distinctive approaches that
      they introduced for regulating occupational exposure to toxic substances.
AB  - The Occupational Safety and Health Administration (OSHA) has regulated
      occupational exposure to asbestos since 1971. Since issuing its first asbestos
      standard, OSHA has modified it several times in response to new information about
      the health risk of exposure and concern expressed by workers and public health
      groups. As each modification has reduced worker exposure and disease risk, each
      also has introduced new concepts including emphasis on ancillary provisions in
      standards regulating occupational exposure to toxic substances to enhance worker
      health; medical removal protection; two attempts at emergency temporary
      standards; use of historical and objective exposure data to assess worker
      exposure; the need to eliminate significant risk of disease posed by asbestos;
      and the presumption of hazard in absence of exposure information. These and other
      advances have affected all subsequent OSHA standards aimed at reducing
      occupational exposure to toxic substances.

PMID- 11331994
TI  - Carbon black and soot: two different substances.
AB  - Carbon blacks are manufactured under controlled conditions for commercial use
      primarily in the rubber, painting, and printing industries. In contrast, soots
      are unwanted byproducts from the combustion of carbon-based materials for the
      generation of energy or heat, or for the disposal of waste. Unfortunately, the
      terms carbon black and soot often have been used interchangeably; however, carbon
      black is physically and chemically distinct from soot. Greater than 97% of carbon
      black consists of elemental carbon arranged as aciniform particulate. Depending
      on the type of soot, the relative amount of carbon (< 60% of the total particle
      mass), the type of particulate carbon, and particle characteristics (size, shape,
      and heterogeneity) can vary considerably. For both carbon black and soot, other
      elements and chemical compounds are associated with the particulate carbon. Total
      inorganics (ash) represent < 1% of the carbon black particle mass. Organic
      compounds can be extracted from particle surfaces (solvent extractable fraction
      [SOF]), and for carbon black, also are < 1% of the particle mass. Soots have much
      greater percentages of ash, SOF, or both, than carbon black. There has been
      concern about the adsorbed organic compounds because of potential biologic
      activity. For carbon black, the SOF is strongly adherent to carbon surfaces and
      is not released by biological fluids. The types of organic compounds consist
      primarily of unsubstituted polycyclic aromatic hydrocarbons and are not as
      biologically potent as those compounds present in soot. Thus, carbon black is
      distinctly different from soot, and when discussing potential health effects,
      care must be taken to differentiate between the two types of carbon-based
      particles.

PMID- 11331995
TI  - Validity of generic risk factors and the strain index for predicting nontraumatic
      distal upper extremity morbidity.
AB  - Nine individual generic risk factors, eight combinations of generic risk factors,
      the presence of any generic risk factor, and the Strain Index were evaluated for
      56 jobs by 2 evaluators blinded to morbidity measures. Jobs then were assigned to
      dichotomous hazard classifications (problem versus safe) according to
      recommendations from the literature. OSHA 200 logs were used to ascertain
      historical evidence of distal upper extremity (DUE) morbidity, and jobs were
      assigned to a dichotomous morbidity classification (positive versus negative)
      using none versus one or more recorded cases as the criterion. Evidence of
      association and measures of predictive validity were evaluated by comparing
      hazard and morbidity classifications using 2 x 2 contingency tables. Five
      individual generic risk factors, three generic risk factor combinations, and the
      presence of any generic risk factor were not associated with morbidity
      classification. The odds ratio estimates among the four individual generic risk
      factors and the five combinations of generic risk factors associated with DUE
      morbidity varied from 3.3-36.0. The Strain Index had the largest estimated odds
      ratio of any exposure factor at 108.3. The exposure methods were grouped
      according to patterns of predictive validity. With one exception, the individual
      generic risk factors and their combinations had high sensitivity with low
      specificity (many false-positives), low sensitivity with high specificity (many
      false-negatives), or low sensitivity with low specificity. The only generic risk
      factor that demonstrated reasonable predictive validity was the use of gloves-
      its sensitivity, specificity, positive predictive value, and negative predictive
      value were equal to 0.75. The Strain Index performed better than any of the
      individual or combinations of generic risk factors. Its sensitivity, specificity,
      positive predictive value, and negative predictive value were all approximately
      0.90.

PMID- 11331996
TI  - An evaluation of factors affecting hazardous waste workers' use of respiratory
      protective equipment.
AB  - The purpose of this study was to describe the perceptions of a group of hazardous
      waste workers about their workplace hazards and to understand their beliefs and
      attitudes about the use of respiratory protective equipment (RPE). There were two
      phases of data collection: (1) interviews to identify factors that influence
      respirator use and (2) a written survey to evaluate the importance of these
      factors. This article describes the findings from the written survey completed by
      255 eligible respondents (return rate = 46.5%, 255/548). Subjects used a
      weighting system to score 18 identified factors that influence the use of RPE.
      Scores were compared according to type of respirator, frequency of use, and
      associated health symptoms. The factors that had the most positive influence on
      respirator use were concern about work exposure, fit-testing, and training. The
      most negative influences were communication, personal comfort, effect on vision,
      structural environment, and fatigue. More frequent users (once per month or more)
      were significantly more likely to view fit-testing, health effects, and effects
      on vision negatively than were less frequent users. Persons who reported health
      symptoms associated with respirator use had more negative scores than persons
      without health symptoms. Workers categorized as laborers were more likely to be
      frequent respirator users and to wear supplied-air respirators, and were
      significantly more likely to view vulnerability to disease negatively, than were
      other worker groups. The findings from this study indicate that respiratory
      protection programs must extend beyond training and education; to be maximally
      effective, health professionals must be responsive to the specific concerns of
      the workers.

PMID- 11331997
TI  - A comparison of solid sampler methods for the determination of hexamethylene
      based isocyanates in spray-painting operations.
AB  - A polyurethane foam sponge impregnated with 1-(2-methoxyphenyl) piperazine in
      dimethylsulfoxide was mounted in both cassette and inhalable organic monitor
      samplers and these were then compared with a dual-filter cassette. The samplers
      were used for the collection of hexamethylene diisocyanate (HDI) monomer and
      oligomers during actual spray-painting operations. The dual filter cassettes were
      positioned on a mannequin. The polyurethane foam cassette (PUF CAS) and
      polyurethane foam inhalable organic monitor (PUF IOM) samplers were positioned on
      a cart in the same maximum overspray area. Data from this pilot study suggest
      that there is no significant difference (P < 0.05, n = 6) in the amount of HDI
      monomer obtained with the PUF IOM sampler when compared with the amount obtained
      from the dual filter cassette. The data also suggest that the PUF IOM sampler
      yields a higher amount of HDI oligomer than either the dual filter cassette or
      the PUF CAS sampler, neither of which exhibited a significant difference (P <
      0.05, n = 6) from each other.

PMID- 11331998
TI  - New antenatal care schedules.

PMID- 11331999
TI  - A lorry driver with a urethral discharge.

PMID- 11332000
TI  - Key developments in women's health.

PMID- 11332001
TI  - Early pregnancy loss.

PMID- 11332002
TI  - Managing ovarian cancer--a GP guide.

PMID- 11332003
TI  - Helping the woman with sexual dysfunction.

PMID- 11332004
TI  - New surgical options for menorrhagia.

PMID- 11332005
TI  - The treatment of endometriosis.

PMID- 11332006
TI  - Understanding insulin in day-to-day practice.

PMID- 11332007
TI  - Diagnosing persistent childhood cough.

PMID- 11332010
TI  - [What all our readers have experiences... My most stressful emergency].

PMID- 11332008
TI  - Diagnosing common tongue lesions.

PMID- 11332011
TI  - [Reducing the need for cortisone. Does eucalyptus oil work in asthma? (interview
      by Brigitte Moreano].

PMID- 11332012
TI  - [Neuralgia after herpes zoster. Dealing with the trouble at the (nerve) roots].

PMID- 11332013
TI  - [Olive oil prevents coronary heart disease. Especially diabetics profit].

PMID- 11332014
TI  - [Acute cholecystitis. Do you send the patient to the operating room or to bed?].
AB  - Acute cholecystitis is increasingly becoming a disease of the elderly. The
      condition begins with colic-like pain in the upper abdomen radiating to the right
      shoulder, and is accompanied by fever, nausea and vomiting. The diagnosis is
      confirmed by tenderness and palpable resistance in the right upper abdomen.
      Ultrasound detects the stone in 95% of cases, and confirms the diagnosis.
      Differential diagnostic considerations include appendicitis, duodenal or gastric
      ulcer, and myocardial infarction. Early cholecystectomy is associated with a low
      complication rate which, however, increases, the longer the intervention is
      delayed. Laparoscopic cholecystectomy has a lower complication rate and a reduced
      hospital stay; the reported mortality rate is between 0% and 3.5%. Conventional
      cholecystectomy is recommended when there is concomitant choledocholithiasis and
      no possibility of carrying out ERCP, and in patients with previous upper
      abdominal surgery. Conservative treatment is applied when the patient refuses
      surgery or is at high risk from anaesthesia.

PMID- 11332015
TI  - [Diagnosis of acute cholecystitis. Ultrasound diagnosis is reliable].
AB  - In the presence of typical ultrasonographic signs (Murphy's sign, established
      pericholecystitis) in patients with a relevant history and clinical presentation,
      diagnosis of acute cholecystitis can be established with a high degree of
      accuracy. As a non-invasive method, ultrasound can be used at the bedside of the
      severely ill patients, thus enabling the more economical use of more
      sophisticated and expensive examination methods. In the acute stage, the urgency
      of surgical intervention can be assessed. During follow-up, the effectiveness of
      conservative measures can be checked, failed treatment detected early on, and
      complications avoided. In high-risk patients, interventional procedures
      (puncture, percutaneous drainage) can be performed under US-control. Thus, US is
      the diagnostic modality of first choice for the diagnosis of acute cholecystitis.
      It has relevance for decision-taking, and is an indispensable procedure in the
      emergency setting.

PMID- 11332016
TI  - [Emergencies in general practice, 8. Acute leg pain].

PMID- 11332017
TI  - [Phytotherapy: academic medicine or natural healing? Medicinal drugs from the
      medical viewpoint].

PMID- 11332018
TI  - [When the psyche interferes with sex. Joyless in bed].

PMID- 11332019
TI  - [Diagnostic series. Helicobacter pylori infections rapidly recognized].

PMID- 11332021
TI  - [Chronic wounds heal pain-free. The comeback of fly maggots].

PMID- 11332020
TI  - [Decreasing blood lipids for prevention of coronary heart disease--discussion of
      the "permissive LDL level". Diagnostic imaging facilitates therapeutic decision].

PMID- 11332022
TI  - [Chronic hepatitis C. Better treatment outcome with pegylated interferon].

PMID- 11332023
TI  - [Oral cytostatic drug in colorectal carcinoma. Selective tumor therapy at home].

PMID- 11332024
TI  - [Ambulatory therapy of thrombosis with low molecular weight heparin. Further
      simplification by one-time administration].

PMID- 11332025
TI  - [Atherosclerosis. High dosage ACE inhibitor keeps event rate under control].

PMID- 11332026
TI  - [Be available to deal with the sexual problems of your patients!].

PMID- 11332027
TI  - Chlorin-type photosensitizers photochemically derived from vinyl porphyrins.
AB  - The reaction of singlet oxygen with four vinyl-substituted dicarboxylic
      porphyrins, vinyldeuteroporphyrin (VD), ethylvinyldeuteroporphyrin (EVD),
      hydroxyethylvinyldeuteroporphyrin (HVD) and protoporphyrin (PP) in organic
      solutions is investigated. The main products, the "hydroxyaldehyde" chlorin-type
      derivatives, are formed with a concentration-dependent photochemical quantum
      yield that reaches a maximum of 7.4 +/- 1.6 x 10(-3). However, owing to the high
      turnover of singlet-oxygen production, these chlorin-type compounds are easily
      prepared photochemically with a chemical yield of 70% and little side product
      formation. In chemical ionization mass spectrometry, these compounds display an
      unusual fragmentation with a loss of 16 mass units. This is attributed to the
      loss of the oxygen bound to the saturated carbon of the modified pyrrole unit.
      All these compounds sensitize the formation of singlet oxygen with a yield around
      0.8. They interact with singlet oxygen with rate constants of 5 x 10(6)-9 x 10(6)
      M-1 s-1, lower than those measured for vinyl porphyrins. These data are likely to
      help in the characterization of photoproducts of vinyl porphyrins relevant to
      photodynamic therapy (PP, HVD). As exemplified with VD and EVD, they also point
      out the reaction of singlet oxygen as an efficient route to chlorin-type
      photosensitizers.

PMID- 11332028
TI  - Direct and sensitized photoprocesses of bis-benzimidazole dyes and the effects of
      surfactants and DNA.
AB  - The photoprocesses of two bis-benzimidazole dyes, Hoechst 33258 (1) and an
      analog, where the phenolic group in p-position is replaced by an ethoxy group,
      Hoechst 33342 (2), were studied. For 1 and 2 in aqueous solution the quantum
      yield of fluorescence is strongly pH dependent; it decreases from a maximum value
      of phi f = 0.4 at pH 5 to phi f = 0.02 at pH 8. The effects of absorption and
      fluorescence, induced by sodium dodecyl sulfate surfactants below and above the
      critical micelle concentration and by double-stranded DNA, are interpreted by
      assuming that in bulk aqueous solution the dyes are essentially present as
      monomers. The strong enhancement of phi f, when the dye is bound to double
      stranded DNA or solubilized in micelles, is suggested to be due to different
      environments at the benzimidazole rings. A quinoid intermediate with absorption
      maximum at 380 nm is formed for 1 at neutral pH using lambda exc = 248 or 308 nm.
      N-centered radicals of 1 or 2 in aqueous solution were observed by laser flash
      photolysis after electron ejection using wavelengths of 193 or 248 nm (mono and
      biphotonic, respectively). The precursor radical cation escaped observation but
      is transformed into the above radicals by deprotonation. Electron transfer from 1
      in aqueous solution to triplet acetone takes place, and subsequent deprotonation
      is proposed to yield N-centered radicals. In addition, energy transfer from
      acetone to 1 is suggested, leading to T-T absorption with the maximum at 700 nm.
      The photoprocesses are discussed and the results compared with those known from
      pulse radiolysis.

PMID- 11332029
TI  - Girard's reagent P derivative of beta-Apo-8'-carotenal: a potent photoprotective
      agent.
AB  - A cationic carotenoid derivative (GRP-carotenal) was synthesized by the reaction
      of Girard's reagent P and beta-apo-8'-carotenal. The singlet-oxygen quenching
      constants for GRP-carotenal were 1.3 +/- 0.1 x 10(10) and 1.0 +/- 0.1 x 10(10) M
      1 s-1 in acetonitrile and in detergent micelles, respectively. Photosensitized
      damage to K562 leukemia cells from cis-di(4-sulfonatophenyl)diphenylporphine,
      hypericin and protoporphyrin IX was inhibited by GRP-carotenal under conditions
      where beta-apo-8'-carotenal, beta-carotene and crocetin were ineffective. The
      unique cytoprotective properties of GRP-carotenal, relative to the other
      carotenoids studied, could not be explained by the differences in the cell
      content of the various carotenoids or by the changes in the cell content of the
      photosensitizers used. Photosensitizer fluorescence from labeled K562 cells was
      reduced by GRP-carotenal but not by the other carotenoids studied. The novel
      photoprotective properties of GRP-carotenal may be due to its subcellular
      distribution. In photosensitizer-containing detergent micelles, novel properties
      of GRP-carotenal were not apparent. None of the carotenoids studied reduced
      photosensitizer fluorescence or singlet-oxygen generation. Singlet-oxygen
      quenching by GRP-carotenal and by beta-apo-8'-carotenal were roughly the same.
      Crocetin has a singlet-oxygen quenching constant that is about a factor of five
      lower. Singlet-oxygen quenching by beta-carotene was limited by its aggregation.

PMID- 11332030
TI  - Mechanism of lipid peroxidation photosensitized by tiaprofenic acid: product
      studies using linoleic acid and 1,4-cyclohexadienes as model substrates.
AB  - A careful study of the linoleic acid hydroperoxide (LOOH) profile obtained upon
      peroxidation of linoleic acid (LA) photosensitized by tiaprofenic acid (TPA) and
      analogous ketones has been undertaken to distinguish between type-I and type-II
      photoperoxidation mechanisms. 1,4-Cyclohexadiene and 1,2-dimethylcyclohexa-2,5
      dienecarboxylic acid (CHDCA) have also been used as models for LA since they also
      have double allylic systems. Coirradiation of LA with TPA and
      decarboxytiaprofenic acid (DTPA) in acetonitrile and micellar media produced
      significant amounts of conjugated dienic LOOH. The cis,trans to trans,trans ratio
      depended on the irradiation time; thus, this parameter is an ambiguous tool for
      mechanistic assignment. An interesting finding was the decrease of the LOOH level
      after long irradiation times in mixtures photooxidized by DTPA, which is
      attributed to quenching of the DTPA triplet by the generated dienic LOOH. High
      performance liquid chromatography analyses confirmed that the main pathway
      operating in photodynamic lipid peroxidation sensitized by (D)TPA is a type-I
      mechanism. However, product studies using CHDCA have clearly shown that a type-II
      mechanism is also operating and might contribute to the overall photooxidation
      process in a significant way.

PMID- 11332031
TI  - Albedo-enhanced maximum UV irradiance--measured on surfaces oriented normal to
      the sun.
AB  - UV radiation measured on normal-to-the-sun-oriented surfaces can show
      significantly higher global UV irradiance values compared to measurements on
      horizontal receivers. The direct component is amplified by the inverse cosine of
      the zenith angle, but over surfaces with high local albedo this accounts for only
      about half of the signal rise of global irradiance. The signal rise of the
      diffuse component, however, is strongly related to local albedo and solar
      elevation, which is demonstrated by 2 years of measurements of direct, diffuse,
      global, reflected and global normal-to-the-sun erythemal effective UV irradiance
      (UVery). Global UVery signal rises, on normal-to-the-sun-oriented versus
      horizontal receivers, of up to 65% were measured on fresh snow and solar
      elevation angles below 30 degrees. An empirical expression has been deduced from
      the measurements relating the ratio of normal-to-the-sun versus horizontal
      measurements of global UVery to surface albedo and solar elevation. This allows
      one to calculate the maximum global UVery irradiance levels which are to be
      expected on normal-to-the-sun-oriented surfaces with respect to horizontal
      measurements or model calculations.

PMID- 11332032
TI  - Exacerbating effect of vitamin E supplementation on DNA damage induced in
      cultured human normal fibroblasts by UVA radiation.
AB  - The effects of vitamin E supplementation were evaluated in cultured human normal
      fibroblasts exposed to ultraviolet A radiation (320-380 nm) (UVA). Cells were
      incubated in medium containing alpha-tocopherol, alpha-tocopherol acetate or the
      synthetic analog Trolox for 24 h prior to UVA exposure. DNA damage in the form of
      frank breaks and alkali-labile sites, collectively termed single-strand breaks
      (SSB), was assayed by the technique of single cell gel electrophoresis (comet
      assay), immediately following irradiation or after different repair periods. The
      generation of hydrogen peroxide (H2O2) and superoxide ion (O2.-) was measured by
      flow cytometry through the oxidation of indicators into fluorescent dyes. It was
      observed that pretreatment of cells with any form of vitamin E resulted in an
      increased susceptibility to the photoinduction of DNA SSB and in a longer
      persistence of damage, whereas no significant change was observed in the
      production of H2O2 and O2.- reactive oxygen species, compared to untreated
      controls. These findings indicate that in human normal fibroblasts, exogenously
      added vitamin E exerts a promoting activity on DNA damage upon UVA irradiation
      and might lead to increased cytotoxic and mutagenic risks.

PMID- 11332033
TI  - Bystander effects in cell death induced by photodynamic treatment UVA radiation
      and inhibitors of ATP synthesis.
AB  - Confluent layers of MDCK II cells were treated with four different
      photosensitizers (a purified version of hematoporphyrin derivative [Photofrin],
      tetra(3-hydroxyphenyl)porphine [3-THPP], meso-tetra(4-sulphonatophenyl)porphine
      [TPPS4] and ALA-induced Protoporphyrin IX) and irradiated with blue light, with
      UVA without exogenous photosensitizers, or incubated with the metabolic
      inhibitors carbonyl cyanide m-chlorophenylhydrazone and 2-deoxy-D-glucose.
      Necrotic and apoptotic cells were detected about 4 h later by fluorescence
      microscopy. Dead cells appeared in distinct clusters in the confluent layers. The
      number of dead cells in these clusters was determined by manual counting and
      image analysis. Forty-one of the 43 experimental distributions of dead cells in
      clusters were found to be significantly different from a Monte Carlo simulation
      of the distribution of independently inactivated cells. However, a Monte Carlo
      simulation model, assuming that each dead cell increased the probability of
      inactivation of adjacent cells, fitted 34 of the 43 observed distributions of
      dead cells in clusters, indicating a significant bystander effect for all the
      investigated treatments. The bystander-effect model parameter, defined as a
      cell's increase in probability of dying when it has dead neighbors, was
      significantly lower for 3-THPP-PDT and TPPS4-PDT than for Photofrin-PDT, ALA-PDT
      and treatment with metabolic inhibitors.

PMID- 11332034
TI  - Evaluation of different photosensitizers for use in photochemical gene
      transfection.
AB  - Many potentially therapeutic macromolecules, e.g. transgenes used in gene
      therapy, are taken into the cells by endocytosis, and have to be liberated from
      endocytic vesicles in order to express a therapeutic function. To achieve this we
      have developed a new technology, named photochemical internalization (PCI), based
      on photochemical reactions inducing rupture of endocytic vesicles. The aim of
      this study was to clarify which properties of photosensitizers are important for
      obtaining the PCI effect improving gene transfection. The photochemical effect on
      transfection of human melanoma THX cells has been studied employing
      photosensitizers with different physicochemical properties and using two gene
      delivery vectors: the cationic polypeptide polylysine and the cationic lipid 1,2
      dioleoyl-3-trimethylammonium-propane (DOTAP). Photochemical treatment by
      photosensitizers that do not localize in endocytic vesicles (tetra[3
      hydroxyphenyl]porphyrin and 5-aminolevulinic acid-induced protoporphyrin IX) do
      not stimulate transfection, irrespective of the gene delivery vector. In
      contrast, photosensitizers localized in endocytic vesicles stimulate polylysine
      mediated transfection, and amphiphilic photosensitizers (disulfonated aluminium
      phthalocyanine [AlPcS2a] and meso-tetraphenylporphynes) show the strongest
      positive effect, inducing approximately 10-fold increase in transfection
      efficiency. In contrast, DOTAP-mediated transfection is inhibited by all
      photochemical treatments irrespective of the photosensitizer used. Neither
      AlPcS2a nor Photofrin affects the uptake of the transfecting DNA over the plasma
      membrane, therefore photochemical permeabilization of endocytic vesicles seems to
      be the most likely mechanism responsible for the positive PCI effect on gene
      transfection.

PMID- 11332035
TI  - In vivo brain tumor demarcation using optical spectroscopy.
AB  - The applicability of optical spectroscopy for intraoperative detection of brain
      tumors/tumor margins was investigated in a pilot clinical trial consisting of 26
      brain tumor patients. The results of this clinical trial suggest that brain
      tumors and infiltrating tumor margins (ITM) can be effectively separated from
      normal brain tissues in vivo using combined autofluorescence and diffuse
      reflectance spectroscopy. A two-step empirical discrimination algorithm based on
      autofluorescence and diffuse reflectance at 460 and 625 nm was developed. This
      algorithm yields a sensitivity and specificity of 100 and 76%, respectively, in
      differentiating ITM from normal brain tissues. Blood contamination was found to
      be a major obstacle that attenuates the accuracy of brain tumor demarcation using
      optical spectroscopy. Overall, this study indicates that optical spectroscopy has
      the potential to guide brain tumor resection intraoperatively with high
      sensitivity.

PMID- 11332036
TI  - Interaction between photodynamic therapy and BCG immunotherapy responsible for
      the reduced recurrence of treated mouse tumors.
AB  - Subcutaneous mouse EMT6 tumors were treated by individual or combined regimens of
      a single Bacillus Calmette-Guerin (BCG) vaccine administration and photodynamic
      therapy (PDT). Six clinically relevant photosensitizers characterized by
      different action mechanisms were used: Photofrin, benzoporphyrin derivative,
      tetra(m-hydroxyphenyl)chlorin (foscan), mono-L-aspartylchlorin e6, lutetium
      texaphyrin or zinc phthalocyanine. Irrespective of the type of photosensitizer
      used, the optimized BCG protocols improved the cure rate of PDT-treated tumors.
      This indicates that the interaction does not take place during the early phase of
      tumor ablation but at later events involved in preventing tumor recurrence.
      Beneficial effects on tumor cure were observed even when the BCG injection was
      delayed to 7 days after PDT. The accumulation of activated myeloid cells that
      markedly increases in tumors treated by Photofrin-based PDT was not additionally
      affected by BCG treatment. However, the incidence of immune memory T cells in
      tumor-draining lymph nodes that almost doubled at 6 days after Photofrin-PDT
      further increased close to three-fold with adjuvant BCG. This suggests that BCG
      immunotherapy amplifies the T-lymphocyte-mediated immune response against PDT
      treated tumors. Since both these modalities are established for the treatment of
      superficial bladder carcinomas, use of their combination for this condition
      should be clinically tested.

PMID- 11332037
TI  - Photodynamic therapy for malignant mesothelioma: preclinical studies for
      optimization of treatment protocols.
AB  - Effective photodynamic therapy (PDT) depends on the optimization of factors such
      as drug dose, drug-light interval, fluence rate and total light dose (or
      fluence). In addition sufficient oxygen has to be present for the photochemical
      reaction to occur. Oxygen deficits may arise during PDT if the photochemical
      reaction consumes oxygen more rapidly than it can be replenished, and this could
      limit the efficacy of PDT. In this study we investigated the influence of the
      drug-light interval, illumination-fluence rate and total fluence on PDT efficacy
      for the photosensitizer meta-tetrahydroxyphenylchlorin (mTHPC). The effect of
      increasing the oxygenation status of tumors during PDT was also investigated. PDT
      response was assessed from tumor-growth delay and from cures for human malignant
      mesothelioma xenografts grown in nude mice. Tumor-bearing mice were injected
      intravenously with 0.15 or 0.3 mg.kg-1 mTHPC, and after intervals of 24-120 h,
      the subcutaneous tumors were illuminated with laser light (652 nm) at fluence
      rates of 20, 100 or 200 mW.cm-2. Tumor response was strongly dependent on the
      drug-light interval. Illumination at 24 h after photosensitization was always
      significantly more effective than illumination at 72 or 120 h. For a drug-light
      interval of 24 h the tumor response increased with total fluence, but for longer
      drug-light intervals even high total fluences failed to produce a significant
      delay in tumor regrowth. No fluence-rate dependence of PDT response was
      demonstrated in these studies. Nicotinamide injection and carbogen breathing
      significantly increased tumor oxygenation and increased the tumor response for
      PDT schedules with illumination at 24 h after photosensitizer injection.

PMID- 11332038
TI  - Photosensitization-induced calcium overload in cardiac cells: direct link to
      membrane permeabilization and calcium influx.
AB  - The purpose of the present study was to gain new insight regarding the role
      membrane permeabilization plays in the photosensitization-induced increase in
      intracellular calcium concentration. During continuous rose bengal
      photosensitization we monitored the contractile state (relaxed or
      hypercontracted) of isolated frog cardiac cells and assessed the
      photosensitization-induced membrane-leak conductance. We investigated the effects
      of irradiance, extracellular calcium concentration, intracellular chelation of
      calcium and substitution of tetraethylammonium (TEA) for extracellular sodium. We
      found that with 2 and 5 mM extracellular calcium cell hypercontracture occurred
      when leak conductance reached values on the order of 6-7 nS, independent of the
      illumination duration required to reach this conductance. With 0.5 mM calcium
      hypercontracture occurred when leak conductance reached values on the order of 11
      nS. Chelation of intracellular calcium delayed the onset of cell hypercontracture
      and increased by two- to three-fold the leak conductance at the initiation of
      cell hypercontracture. Substitution of TEA for extracellular sodium did not
      affect the time to contracture onset but reduced leak conductance at contracture
      onset nearly three-fold. We discuss how our results support the conclusion that
      photosensitization induces an increase in intracellular calcium concentration via
      calcium influx through the transmembrane-permeability pathway opened by the
      photosensitization process.

PMID- 11332039
TI  - Topical delivery of retinoids counteracts the UVB-induced epidermal vitamin A
      depletion in hairless mouse.
AB  - UVB irradiation depletes all-trans-retinol (ROL) and all-trans-retinyl esters
      (RE) from the hairless mouse epidermis. Prevention of this may be of relevance in
      counter-acting the long-term side effects of UVB exposure. We studied the effects
      of a topical treatment with natural retinoids before and after UVB exposure on
      three parameters involved in vitamin A metabolism: the amount of epidermal ROL
      and RE, the level of functional cellular retinol-binding protein I (CRBP-I),
      which is likely to protect ROL from UVB, as well as the cytosolic and microsomal
      enzyme activities which generate ROL and RE, i.e. all-trans-retinaldehyde (RAL)
      reductase, acylCoA:retinol acyltransferase (ARAT) and retinyl-ester hydrolase
      (REH). Topical pretreatment with retinoids promoted a dramatic increase of
      epidermal ROL, RE and CRBP-I levels, a transient increase of RAL reductase and
      ARAT activities as well as a decreased activity of REH, indicating a direction of
      epidermal vitamin A metabolism toward storage. In untreated mice UVB irradiation
      induced a depletion of epidermal ROL and RE in 10 min and a 50% decrease of CRBP
      I after 24 h. In mice treated with topical retinoids, and then exposed to UVB,
      epidermal RE levels were higher than in vehicle-treated, nonirradiated mice. In
      contrast, ROL was as much depleted after UVB in pretreated as in untreated
      animals in spite of an induction of CRBP-I, indicating that CRBP-I does not
      actually protect ROL from UVB-induced depletion in this model. However, the
      reconstitution of both epidermal ROL and RE, after their depletion induced by
      UVB, was accelerated by previous topical treatment with RAL. Our results indicate
      that topical delivery of retinoids partly counteracts UVB-induced vitamin A
      depletion and promotes recovery.

PMID- 11332040
TI  - UVA exposure affects UVB and cis-urocanic acid-induced systemic suppression of
      immune responses in Listeria monocytogenes-infected Balb/c mice.
AB  - Ultraviolet radiation can inhibit immune responses locally as well as
      systemically. Such effects have been measured in animals and humans exposed to
      ultraviolet B (wavelength 280-315 nm) (UVB) and ultraviolet A (315-400 nm) (UVA).
      The precise wavelength dependence is important for the identification of possible
      molecular targets and for assessments of risk of different artificial UV sources
      and solar UV. In such analyses, it is commonly assumed that radiation energy from
      each wavelength contributes to the effect independent of the other wavelengths.
      Here we show that this assumption does not hold good. In the present study, it
      was investigated whether exposure to broadband UVA or longwave ultraviolet A 1
      (340-400 nm) (UVA 1) prior to the standard immunosuppressive UVB protocol might
      modulate the immunosuppressive effects induced by UVB. Preexposure to broadband
      UVA or longwave UVA 1, 1 day prior to the standard immunosuppressive UVB
      protocol, inhibited the UVB-induced suppression of delayed type hypersensitivity
      (DTH) to Listeria monocytogenes significantly. This effect was not associated
      with restoring the number of interleukin (IL-12)-positive cells in the spleen.
      Since isomerization of trans-urocanic acid (UCA) into the immunosuppressive cis
      UCA isomer plays a crucial role in UVB-induced immunomodulation, in a second set
      of experiments it was investigated whether immunosuppression induced by cis-UCA
      might also be downregulated by preexposure to UVA. Animals were exposed to broad
      band UVA or longwave UVA 1 prior to application of an immunosuppressive dose of
      cis- or trans-UCA as a control. Both UVA and UVA 1 appear to inhibit the cis-UCA
      induced systemic immunosuppression (DTH and IL-12) to L. monocytogenes. These
      studies clearly show that UVA radiation modulates both UVB and cis-UCA-induced
      immunomodulation. In general, our studies indicate that both broadband UVA and
      longwave UVA 1 could induce modulation of UVB and cis-UCA-induced
      immunomodulation. As sunlight contains both UVA and UVB radiation the balance
      between these two radiations apparently determines the net immunomodulatory
      effect.

PMID- 11332041
TI  - Photoreactivation of alloxanthine-inhibited xanthine oxidase.
AB  - Alloxanthine-inhibited xanthine oxidase (XOD) was found to be photoreactivated by
      irradiation of light of wavelengths in the range of 340-430 nm. The enzyme
      activity can be fully controlled to be on or off by many dark-light cycles.
      Electron spin resonance measurement shows the appearance of the molybdenum (V)
      ion and the reduced form of flavin adenine dinucleotide (FADH.) radical signals
      after irradiation of the alloxanthine-XOD complex. Electronic-absorption spectrum
      also shows the bleaching of Fe/S and flavin adenine dinucleotide chromophores at
      375 and 450 nm as well as broad-band absorption of FADH. in the range of 500-700
      nm. The quantum yield of photoreactivation of the enzyme activity is
      approximately 0.06. A photoinduced intraenzyme electron-transfer model is
      proposed to rationalize the photoreactivation process.

PMID- 11332042
TI  - The history of the UV radiation climate of the earth--theoretical and space-based
      observations.
AB  - In the Archean era (3.8-2.5 Ga ago) the Earth probably lacked a protective ozone
      column. Using data obtained in the Earth's orbit on the inactivation of Bacillus
      subtilis spores we quantitatively estimate the potential biological effects of
      such an environment. We combine this practical data with theoretical calculations
      to propose a history of the potential UV stress on the surface of the Earth over
      time. The data suggest that an effective ozone column was established at a pO2 of
      approximately 5 x 10(-3) present atmospheric level. The improvement in the UV
      environment on the early Proterozoic Earth might have been a much more rapid
      event than has previously been supposed, with DNA damage rates dropping by two
      orders of magnitude in the space of just a few tens of millions of years. We
      postulate that a coupling between reduced UV stress and increased pO2 production
      could have contributed toward a positive feedback in the production of ozone in
      the early Proterozoic atmosphere. This would contribute to the apparent rapidity
      of the oxidation event. The data provide an evolutionary perspective on present
      day Antarctic ozone depletion.

PMID- 11332043
TI  - [Surgical treatment of biliary lithiasis: where does the future lie?].

PMID- 11332044
TI  - [Transmission of hepatitis C virus by dialysis: myth or reality? New perspective
      with molecular studies].

PMID- 11332045
TI  - [Mechanical hearts: where are we heading?].

PMID- 11332046
TI  - Management of choledocholithiasis found during laparoscopic cholecystectomy: a
      strategy based on the use of postoperative endoscopic retrograde cholangiography
      and sphincterotomy.
AB  - BACKGROUND: Several strategies have been proposed for the diagnosis and
      management of common bile duct stones in candidates for laparoscopic
      cholecystectomy. METHODS: Clinical characteristics, treatment, and outcome of
      five patients in whom CBDS were demonstrated by intraoperative cholangiography
      during a laparoscopic cholecystectomy were analyzed. All patients were treated by
      endoscopic sphincterotomy. Post-treatment outcome was emphasized. RESULTS: Mean
      age of the patients was 55 years. Four were female and one male. Preoperative
      liver function tests were within normal range in all patients. Duct stones of a
      mean size of 0.8 cm were found in the lower third of the biliary tree. Four were
      retrieved by endoscopic sphincteroplasty using a Dormia basket and in one patient
      after an unsuccessful endoscopic attempt, an open choledochoduodenostomy was
      performed. There were no post-treatment complications. At a mean follow-up of 2
      years no evidence of recurrent common bile duct obstruction has been found in any
      patient. CONCLUSIONS: This small series supports the use of postoperative
      endoscopic retrograde cholangiography and sphincteroplasty in patients with
      unsuspected common bile duct stones found during laparoscopic cholecystectomy.
      Retrieval of the stones immediately after surgery at the operative room is
      recommended.

PMID- 11332047
TI  - [Viral hepatitis C in patients with terminal chronic renal insufficiency. III.
      Viral quantification].
AB  - BACKGROUND: We have previously shown that the prevalence of hepatitis associated
      with the hepatitis C virus (HCV) in patients with end stage renal disease in our
      institution is 10.2%. However, quantification of viral RNA in plasma and its
      relation with clinical variables has never been studied in our patients. Thus,
      the aim of the present work was to quantify the HCV viral load in patients with
      ESRD in dialysis, and to correlate these values with the dialysis modality and
      the viral genotype. METHODS: We performed a transverse, prospective and
      comparative study in patients with HCV infection in hemodialysis, continuous
      ambulatory peritoneal dialysis and patients in peritoneal dialysis, but with
      history of hemodialysis. Viral load was quantified with RT-PCR by using a
      commercial kit known as Amplicor HCV 2.0. Clinical variables studied were: age,
      gender, end stage renal disease etiology, modality and time in dialysis,
      transfusions, serum albumin, aminotransferases, blood urea nitrogen, and serum
      creatinine. RESULTS: Twenty four patients in dialysis with HCV infection entered
      into the study. Of these patients, 25% were on peritoneal dialysis, 29% on
      peritoneal dialysis with history of hemodialysis, and 46% were in hemodialysis.
      The average viral load (copies x 10(6)/mL) was 1.41 +/- 3.01. Viral load was
      lower in patients on peritoneal dialysis than in patients treated, or with
      history of hemodialysis (0.20 +/- 0.12 vs 2.04 +/- 0.88; p < 0.05). We observed
      no differences in viral load among patients with different viral genotypes.
      DISCUSSION: The average viral load of our patients in dialysis is lower than the
      levels usually observed in hepatitis C infected patients without end stage renal
      disease. The lower viral load in patients treated with peritoneal dialysis, and
      no history of hemodialysis, probably denotes lower risk of chronic liver disease
      in these subpopulation.

PMID- 11332048
TI  - [Aptitude for the critical reading of clinical research articles among psychiatry
      residents].
AB  - OBJECTIVE: To estimate the aptitude for the critical reading of papers of clinic
      research of psychiatry residents of the Mexican Institute of the Social Security
      in Mexico City. METHODS: A total of 34 residents from two hospitals (A and B)
      participated. Measuring instrument with abstracts of published research papers
      and 96 items was constructed to explore their abilities of interpretation,
      discernment and critical reading. Its reliability was of 0.88. RESULTS: The
      median of Hospital A was 11 and Hospital B was 9 and the global of 9.5 (p NS).
      There were no differences of results according to the year of residency (I, II
      and III) nor in the indicators. Most of the participants (n = 26, 76%) had a
      score below 18 which would be the score if answered in a random fashion.
      CONCLUSIONS: Critical reading of the participants was very low. Our results
      suggest that the bibliography sessions of the psychiatry residents were oriented
      to consumption of information and that critical reading of research papers was
      absent or very poor.

PMID- 11332049
TI  - [Clinical manifestations and lethality of descending necrotizing mediastinitis].
AB  - OBJECTIVE: To describe the clinical manifestations, treatment and lethality of a
      series of patients with descending necrotizing mediastinitis (DNM). DESIGN:
      Retrospective study of a series of cases. SITE OF STUDY: The Infectious Diseases
      Hospital (IDH) of the Mexican Social Security Institute, Mexico City; a national
      reference hospital. PATIENTS AND METHODS: From January 1996 through December
      1998, 18 consecutive patients with diagnostic criteria for DNM were treated in
      the IDH. Demographic variables, precedents, clinical manifestations,
      characteristics of paraclinical studies, and treatment results were recollected
      from the chart of each patient. We made a comparison between patients who
      survived and the patients who died. RESULTS: The mean age of the patients was
      48.8 +/- 19.1 years; 13 (72.5%) were men. Nine (50%) had an underlying disease,
      being diabetes mellitus the most frequent one. In 13 (72.5%) cases an odontogenic
      abscess was the original infection; three (16.6%) patients had retropharyngeal
      abscesses. The mean time between the beginning of symptoms and admission to the
      hospital was 10.6 +/- 6.7 days. The most frequent symptoms were fever, dyspnea,
      dysphagia, and hypotension. The treatment was medical and surgical in all cases,
      with antibiotics, thoracotomy, drainage and debridement. The most frequent
      complications were septic shock, nosocomial pneumonia and ARDS. Nine patients
      died, the lethality rate was 50%. Patients who died had, at admission lower
      leukocytes and platelets counts; higher glycemia, and developed more frequently
      cardiovascular complications and septic shock. CONCLUSIONS: Odontogenic abscesses
      are the most frequent primary infections in patients with DNM. This is an
      infectious problem with high lethality. Septic shock is the principal cause of
      death.

PMID- 11332050
TI  - [In vitro measurement of nitazoxanide sensitivity of 4 Giardia duodenalis
      isolates obtained from different hosts].
AB  - BACKGROUND: In Mexico giardiosis is the most prevalent parasitic disease in
      children. Treatment with antiparasitics derived from: nitroimidazoles,
      benzimidazoles and nitrofuranes have been used; but, some of them have
      undesirable side effects. Recently nitazoxanide (Ntz) was introduced in Mexico;
      however, there are few studies on Giardia duodenalis susceptibility to Ntz.
      OBJECTIVE: To determine G. duodenalis sensitivity to Ntz and compare it to
      tinidazole (Tnz). MATERIAL AND METHODS: Assays were performed in four G.
      duodenalis isolates: INP231087MM, INP210897-AXA1 obtained from humans infections,
      INP170693HG8, INP300693-CP5 from a cat and a dog, respectively. Half million
      trophozoites were exposed to different Ntz or Tnz concentrations in TYI-S-33, for
      24 hours at 37 degrees C. Trophozoite viability was tested by the colorimetric
      method of MTT-tetrazolium salts reduction to MTT-formazan. To analyze
      ultrastructural damage, control and experimental samples were processed by
      standard electron microscopy methods. Experiments were carried out, in a double
      blind in triplicate and repeated four times. Results were analyzed by variance
      analysis. RESULTS: Susceptibility at 100% were in a Ntz concentration ranging
      from 1 microgram to 7 micrograms and in a Tnz concentration ranging from 1
      microgram to 4 micrograms. There were significant differences when sensitivities
      to Ntz were compared between them (P < 0.001). The ultrastructural analysis
      showed changes in trophozoite volume, loss of characteristic shape and swelling.
      CONCLUSIONS: This is the first report of G. duodenalis susceptibility to Ntz
      performed in isolates from different hosts. G. duodenalis isolates were more
      susceptible to Tnz than Ntz.

PMID- 11332051
TI  - [Breast cancer genetics. BRCA1 and BRCA2: the main genes for disease
      predisposition].
AB  - Breast cancer is among the most common world cancers. In Mexico this neoplasm has
      been progressively increasing since 1990 and is expected to continue. The risk
      factors for this disease are age, some reproductive factors, ionizing radiation,
      contraceptives, obesity and high fat diets, among other factors. The main risk
      factor for BC is a positive family history. Several families, in which clustering
      but no mendelian inheritance exists, the BC is due probably to mutations in low
      penetrance genes and/or environmental factors. In families with autosomal
      dominant trait, the BRCA1 and BRCA2 genes are frequently mutated. These genes are
      the two main BC susceptibility genes. BRCA1 predispose to BC and ovarian cancer,
      while BRCA2 mutations predispose to BC in men and women. Both are long genes,
      tumor suppressors, functioning in a cell cycle dependent manner, and it is
      believed that both switch on the transcription of several genes, and participate
      in DNA repair. The mutations profile of these genes is known in developed
      countries, while in Latin America their search has just began. A
      multidisciplinary group most be responsible of the clinical management of
      patients with mutations in BRCA1 and BRCA2, and the risk assignment and Genetic
      counseling most be done carefully.

PMID- 11332052
TI  - [La Revista de Investigacion Clinica becomes a bilingual publication].

PMID- 11332053
TI  - [Rectal cancer: treatment and results].

PMID- 11332054
TI  - [Vitamin D: implications for health and pregnancy].
AB  - Vitamin D gained importance since the discovery of its steroid structure. Vitamin
      D participates in mineral homeostasis, regulation of gene expression, and cell
      differentiation. Recent advances in the study of the enzyme involved in the
      conversion of 25-hydroxyvitamin D3 into 1,25-dihydroxyvitamin D3 (calcitriol), as
      well as the discovery of it's hormone mechanism of action, have led to a better
      knowledge and understanding of vitamin D endocrine system, as well as it's
      implication in health and pregnancy.

PMID- 11332055
TI  - [Hospital infections in intensive care units].

PMID- 11332056
TI  - ANCA-associated necrotizing/granulomatous glomerulonephritis in an elderly
      patient; importance of the renal biopsy.
AB  - ANCA-associated glomerulonephritis may present initially with renal symptoms,
      especially in elderly patients. We report a case of ANCA-associated
      glomerulonephritis in an 80-year-old female presenting with renal insufficiency
      and proteinuria. There was no evidence of systemic illness at admission. The
      major finding in the renal biopsy was the presence of granulomas. Additional
      testing for anti-neutrophil cytoplasmic antibodies (ANCA) was suggested. The ANCA
      test was positive confirming the diagnosis of ANCA-associated
      necrotizing/granulomatous glomerulonephritis. The patient responded well to
      adequate treatment with immunosuppressive therapy. This case demonstrates the
      importance of the renal biopsy in cases of ANCA-associated glomerulonephritis
      presenting with renal symptoms.

PMID- 11332057
TI  - [Should mathematics be the explanatory nucleus of medical knowledge?].

PMID- 11332058
TI  - [Is life possible after blood patch?].

PMID- 11332059
TI  - [Target controlled infusion (TCI) anesthesia using propofol. Assessment of
      training and practice in the operating room].
AB  - OBJECTIVE: To evaluate overall awareness of TCI and the need for training in the
      TCI technique. To assess, among trained anaesthetists, the value of the session
      and the impact of TCI technique on their working practice. STUDY DESIGN: Two
      prospective domestic surveys during the first quarter of 1999. METHODS: Three
      hundred anaesthetists representative of French anaesthetists as a whole, and 336
      anaesthetists who had taken part in a training course. RESULTS: The notoriety of
      TCI was high and greater in the public sector compared with the private sector.
      Almost 3/4 of anaesthetists believed that training was necessary but only four
      anaesthetists out of ten TCI users said they had taken part in training sessions.
      After the training session nine anaesthetists out of ten became TCI users and
      would have recommended the training course despite the low number and variety of
      anaesthetic procedures observed during the practical part of training. The main
      difficulties reported during initial use were the choice of target concentrations
      and the management of drug interactions. Familiarisation to the technique was
      rapid (less than 20 procedures). Despite the lack of long experience (< 6 months
      for more than 2/3 of them), TCI appeared to be more likely used for anaesthesia
      of average duration. CONCLUSIONS: TCI was perceived to be an innovative concept
      with a requirement of a specific training. This preliminary appraisal of training
      sessions was generally satisfactory but underline a need for future training
      sessions focused on practical aspects.

PMID- 11332060
TI  - [Quality assurance program for postoperative pain management: impact of the
      Consensus Conference of the French Society of Anesthesiology and Intensive Care].
AB  - OBJECTIVE: To assess the impact of a pain management quality assurance program
      (PQAP) after abdominal surgery. The means used were mainly based on the French
      Society of anaesthesiology's pain management guidelines. STUDY DESIGN:
      Prospective evaluation using a before after study design: two audits among
      surgical patients: a first one in 1997 before implementation of PQAP, and a
      second one year later. PATIENTS AND METHODS: First, standards were defined
      including objectives about pain relief and patient satisfaction. After analysis
      of discrepancy observed between these objectives and the data of the first audit,
      a pain management program was introduced that included education of physicians,
      nurses and patients, systematic assessment of pain, organized pain relief
      protocols and implementation of modern analgesic technologies. RESULTS: 201
      consecutive inpatients were evaluated in the first audit, and 117 in the second
      one. Comparing the second audit with baseline, the visual analog pain scores
      decreased during the five postoperative days, and the rate of very satisfied
      patients increased (36% versus 26%). 43% of the patients were given a regular
      analgesic medication in 1998 versus 15% in 1997. 65% of medications were
      administered with an effective interval between doses versus 47% in 1997. Patient
      controlled techniques were used in 28% of the cases in 1998 versus 9% in 1997.
      CONCLUSION: The PQAP provided an improvement in efficacy of postoperative pain
      management in our unit, with the help of the overall ward staff, but without
      requiring personnel specially qualified.

PMID- 11332061
TI  - [Addition of clonidine to 0.5% lidocaine for intravenous locoregional
      anesthesia].
AB  - OBJECTIVE: Evaluate the effect of the addition of clonidine to lidocaine on
      postoperative pain after intravenous regional anaesthesia. STUDY DESIGN: Double
      blind prospective study. PATIENTS AND METHODS: Forty-five patients were randomly
      allocated to two groups: group 1 (n = 25) receiving 3 mg.kg-1 of lidocaine 0.5%
      added to saline and group 2 (n = 20) receiving 3 mg.kg-1 of lidocaine 0.5% added
      to clonidine (150 micrograms). Postoperative analgesia was assessed using a
      visual analogue pain score (VAPS) and the time to first analgesic request. The
      incidence of side effects after tourniquet release was noted. Analysis of
      variance, Kruskall Wallis and chi 2 tests were used for statistical analysis. A p
      value of < 0.05 was considered significant. RESULTS: Age, ASA class, duration and
      type of surgery, tourniquet time and sensory block duration were comparable for
      the two groups. The time to first antalgic request after deflation of tourniquet
      was similar in the two groups (38 +/- 15 min versus 44 +/- 19 min), while VAPS
      score was lower (p < 0.05) in the clonidine group (5.2 versus 6.8). The incidence
      of side effects was comparable in the two groups. CONCLUSION: The addition of
      clonidine (150 micrograms) to lidocaine for intravenous regional anaesthesia
      improved postoperative analgesia but in a limited and short-lasting manner.

PMID- 11332062
TI  - [Percutaneous tracheostomy].
AB  - OBJECTIVES: The aim of this study was to evaluate the different techniques of
      percutaneous tracheostomies, their advantages, drawbacks, complications and to
      compare them to standard surgical tracheostomies. This study will consider only
      elective (non emergency) bedside procedures in intensive care units. DATA
      SOURCES: Extraction from Medline database of english and french articles on
      percutaneous tracheostomies and searching along with major review articles. STUDY
      SELECTION: The collected articles were selected according to their qualities
      regarding to their evidence level. In addition to several important or historic
      references, the literature of the five past years was studied. DATA EXTRACTION:
      The articles were reviewed according to their contribution for techniques,
      perioperative and postoperative complications, recent advances, advantages and
      drawbacks of all procedures. Publications addressing recent comparisons between
      surgical and percutaneous tracheostomies were specially studied. DATA SYNTHESIS:
      Four techniques of bedside percutaneous tracheostomies are available and
      marketed, in France: Ciaglia's dilation technique (with multiple or unique
      dilator), Griggs's technique (using a special designed forceps), and Fantoni's
      technique (Trans Laryngeal Tracheostomy). The most spred but also first described
      technique is the Ciaglia's (1985). The most recent articles comparing surgical
      and percutaneous tracheostomies techniques are not able to demonstrate a
      superiority of one of them in terms of feasibility or safety. In other words,
      there should be a slight advantage for the percutaneous tracheostomy regarding to
      the late post-operative complications, as there should be a slight advantage for
      the surgical techniques regarding to the perioperative complications. The
      literature analysis point out firstly the learning curve for percutaneous
      dilational tracheostomy, with a significant decrease of complication incidence
      with the operator's experience and secondly the continuous endoscopic guidance
      seems to increase the safety of the percutaneous procedure. CONCLUSION: Since
      there has been a great deal of percutaneous tracheostomy in the intensive care
      units, the incidence of tracheostomy have increased in those services. There is a
      trend to replace the surgical procedure by the percutaneous one. However,
      according to the potentially jeopardizing complications, percutaneous
      tracheostomy should be done by an experienced operator with the help of a
      continuous endoscopic guidance.

PMID- 11332063
TI  - [Ischemia of a transplanted kidney and hyperlactatemia].
AB  - The authors report four cases of patients presenting with hyperlactatemia
      following renal transplantation. The post-transplantation course of three
      patients who underwent renal transplantation was complicated by occult
      haemorrhage. Excessive blood loss was not evident, the patients were
      haemodynamically stable and their blood pressure, pulse rare and filling pressure
      (central venous pressure) were unremarkable. Late examinations revealed an early
      increase in arterial lactate concentrations a non-aniograp acidosis or lactic
      acidaemia occurred. Surgical decompression was carried on in all patients. An
      increase in the intraabdominal pressure might have caused renal impairment in the
      absence of haemodynamic disturbance, and retroperitoneal haematoma a change in
      the distribution of intrarenal blood flow. Another patient developed a partial
      renal venous thrombosis associated with hyperlactatemia. During this re
      operation, a renal lactate production was measured. The renal cortex is a site of
      lactate clearance. Impaired renal perfusion should result in decreased lactate
      clearance and when the kidney is hypoperfused a lactate production was occur. In
      the absence of any signs of clinical shock, patient at risk of retroperitoneal
      haematoma or presenting with oliguria should benefit from lactate measurements,
      which could help diagnosing severe hypoperfusion of the graft.

PMID- 11332064
TI  - [Febrile coma and multiple organ failure: suspected hemoglobinopathy SC].
AB  - We report the case of febrile fatal coma in a 51-year-old man from Burkina Faso.
      Magnetic resonance imaging (MRI) shows cerebral fat embolism. Haemoglobin
      electrophoresis shows probably haemoglobinopathy SC. A short review of the
      literature demonstrate the need to consider this complication in patients with
      neurological or respiratory disorders, in areas where this disease is highly
      prevalent, irrespective of age. It also emphasizes the diagnostic contribution of
      MRI and discusses the mechanism, the diagnosis as well as the difficulty of
      choosing the appropriate therapeutic course.

PMID- 11332065
TI  - [Quadriplegia secondary to potassium depletion].
AB  - Muscle paralysis due to potassium depletion are unusual. We report the case of a
      patient who developed quadriplegia and language disorders due to potassium
      depletion, following large intestinal resection. Potassium supplementation was
      given intravenously at a rate of 0.25 mmol.kg-1.h-1 during the first 48 h. This
      allowed complete total and rapid recovery from the paralysis.

PMID- 11332066
TI  - [Cerebrovascular accident: differential diagnosis of a compressive spinal
      hematoma].
AB  - We report the case of a 84-year-old patient who developed a monoplegia of the
      left inferior limb after a spinal anaesthesia for femoral neck's fracture. The
      magnetic resonance imaging (MRI) carried out in emergency, eliminated a spinal
      compression. The final diagnosis was a cerebral stroke. This observation leads us
      to discuss the choice of anaesthesia technical, the various aetiologies of a
      neurological trouble after spinal anaesthesia. The appearance of clinical signs
      evoking a spinal haematoma, must make seek by the imagery (MRI or scanner) the
      signs of spinal compression in order to propose an emergency laminectomy. Finally
      we insist on the importance but also on the difficulties of the clinical
      examination in elderly traumatic patients.

PMID- 11332067
TI  - [Assessment of left ventricular diastolic pressure with Doppler
      echocardiography].
AB  - Transthoracic echocardiography is able to provide immediate and relevant
      information in case of respiratory failure. The authors report a case of
      congestive heart failure with normal systolic function. Transmitral and pulmonary
      venous flow velocities have been used to assess left ventricular filling pressure
      and diastolic function.

PMID- 11332068
TI  - [Does a previous blood patch contraindicate spinal anesthesia?].

PMID- 11332069
TI  - [Acute severe hemorrhage by a wound of the inferior thyroid vein during
      percutaneous tracheostomy].

PMID- 11332070
TI  - [Is the use of sevoflurane in closed circuit in pediatric anesthesia really an
      economy?].

PMID- 11332071
TI  - [Cardiac arrest during the concomitant administration of sulprostone and
      noradrenaline].

PMID- 11332072
TI  - [Recommendations for the practice of neurostimulation].

PMID- 11332073
TI  - [Use of central venous catheters according to the Seldinger technique at the
      pleural and peritoneal level].

PMID- 11332074
TI  - [Carcinoid syndrome and bispectral index].

PMID- 11332075
TI  - Confocal image characterization of human papillomavirus DNA sequences revealed
      with Eu in HeLa cell nuclei stained with Hoechst 33342.
AB  - OBJECTIVE: To visualize and localize specific viral DNA sequences revealed with
      Eu by fluorescence in situ hybridization, confocal laser scanning microscopy
      (CLSM) and factor analysis of biomedical image sequences (FAMIS). STUDY DESIGN:
      Human papillomavirus DNA (HPV-DNA) was identified in HeLa cells with biotinylated
      DNA probes recognizing HPV-DNA types 16/18. DNA-DNA hybrids were revealed by a
      three-step immunohistochemical amplification procedure involving an antibiotin
      mouse monoclonal antibody, a biotinylated goat antimouse polyclonal antibody and
      streptavidin-Eu. Cell nuclei were counterstained with Hoechst 33342. Image
      sequences were obtained using a CLSM that made possible ultraviolet excitation.
      The location of fluorescent signals inside cellular preparations was determined
      by FAMIS and selection of filters at emission. Image sequences were summarized
      into a reduced number of images, or factor images, and curves, or factors.
      Factors estimate spectral or temporal patterns and depth emission profiles.
      Factor images correspond to spatial distributions of the different factors.
      RESULTS: We distinguished between Eu corresponding to HPV-DNA hybridization
      signals and nuclear staining by taking into account differences in their spectral
      and temporal patterns and (using their decay rates). CONCLUSION: FAMIS, together
      with CLSM and Eu, made possible the detection and characterization of viral
      papillomavirus DNA sequences in HeLa cells.

PMID- 11332076
TI  - Transforming growth factor-beta pathway in human renal cell carcinoma and
      surrounding normal-appearing renal parenchyma.
AB  - OBJECTIVE: To analyze the role of the transforming growth factor (TGF)-beta
      pathway in renal tumors and to verify whether alterations in TGF-beta 1 pathway
      expression are associated with the grade of tumor differentiation and pathologic
      stage in renal cell carcinomas. STUDY DESIGN: The expression of TGF-beta 1 and
      TGF-beta receptors (T beta RI and T beta RII), SMAD-2 and SMAD-4 was investigated
      by immunohistochemistry in normal peritumoral and tumoral tissue from 53 renal
      cell carcinomas (clear cell type). The gene expression of SMAD-2 and SMAD-4 was
      also studied by reverse transcription polymerase chain reaction (RT-PCR) in
      normal peritumoral and tumoral tissue from 6 of 56 primary tumors. RESULTS: TGF
      beta 1, T beta RI and T beta RII immunoreactivity was more frequent in tumoral
      than in normal peritumoral renal tissue (96.22%, 79.25% and 75.41% vs. 88.37%,
      69.76% and 62.69%), whereas SMAD-2 and SMAD-4 immunoreactivity was more frequent
      in normal peritumoral than in tumoral tissue (23.25% and 30.23% vs. 15.09% and
      7.54%). In tumor areas, immunohistochemical scores were lower for T beta RII than
      for T beta RI and TGF-beta 1 and higher than SMAD-4 and SMAD-2 scores. TGF-beta
      1, T beta RI, T beta RII and SMAD-4 histologic scores correlated with neither the
      histologic grade of malignancy nor TNM clinical stage, whereas SMAD-2 protein
      levels were significantly lower in grade 3 than in grade 1 tumors. In the samples
      of normal kidney and carcinoma studied, RT-PCR detected the correct transcripts
      for SMAD-2 and SMAD-4, indicating that the RNA of the samples analyzed contained
      RNA sequences coding for these genes. CONCLUSION: Our data support the concept
      that the reduction of T beta RII and SMAD proteins in renal cell carcinomas is
      involved in tumor development and suggest an altered TGF-beta/SMAD signaling
      pathway in kidney neoplasia.

PMID- 11332077
TI  - Quantitative cytomorphologic analyses of Papanicolaou-stained smears from oral
      lichen planus.
AB  - OBJECTIVE: To apply quantitative techniques to cytologic smears in order to
      improve the diagnostic sensitivity of cytology in the detection of malignant
      change in the oral cavity. STUDY DESIGN: Eighty-two patients with lesions of oral
      lichen planus were investigated. A total of 247 Papanicolaou-stained buccal
      smears underwent nuclear and cytoplasmic area measurements using a TV image
      analyzer. RESULTS: The cytomorphologic results of this study suggest that lesions
      of oral lichen planus contain smaller cells and nuclei than those observed in
      clinically normal oral mucosal smears. There was a statistically significant
      reduction in nuclear area (P < .001) and cytoplasmic area (P < .05) for the oral
      lichen planus smears. CONCLUSION: The TV image analysis system could provide a
      valuable method of quantifying cell changes in oral smears collected from oral
      mucosa as a method of monitoring lesions of oral lichen planus.

PMID- 11332078
TI  - DNA image cytometry in the differential diagnosis of endometrial hyperplasia and
      adenocarcinoma.
AB  - OBJECTIVE: To test the value of DNA image cytometry in the differential diagnosis
      of hyperplastic endometrial lesions and endometrial carcinoma on a series of 153
      cases of simple hyperplasia (n = 71), complex hyperplasia (n = 28), complex
      atypical hyperplasia (n = 11) and endometrial adenocarcinoma (n = 43). STUDY
      DESIGN: Monolayer smears were prepared from three 50-micron-thick sections by a
      cell separation technique and were stained according to Feulgen. The DNA content
      of 250 epithelial cells, chosen randomly, was determined using a TV image
      analysis system (CM-1, Hund, Wetzlar, Germany). The DNA content of 30 lymphocytes
      served as an internal standard for the normal diploid value in every case.
      Different DNA cytometric parameters and the mean nuclear area were calculated.
      RESULTS: Cases of adenocarcinoma and complex atypical hyperplasia (n = 54) were
      defined as clinically "positive" as these patients are normally treated by
      hysterectomy. The remaining cases of simple and complex hyperplasia (n = 99) were
      interpreted as clinically "negative" as conservative therapy is usually
      preferred. Requesting a specificity of > 90%, high sensitivity rates were
      calculated for ploidy imbalance (94%), mean ploidy (91%), diploid deviation
      quotient (91%), DNA stemline ploidy (87%) and 2c deviation index (85%), based on
      suitable thresholds. Entropy (76%), 5c exceeding events (63%), mean nuclear area
      (48%) and 9c exceeding events (6%) revealed lower sensitivity values. 5c
      Exceeding events (P = .0117) and mean nuclear area (P = .0392) were helpful in
      differentiating between atypical hyperplasia and endometrial carcinoma as the
      data distribution was significantly different with the U test. CONCLUSION: Our
      results indicate that DNA single cell cytometry is a highly relevant tool in the
      differential diagnosis of endometrial lesions and could be used as a
      complementary diagnostic method, especially in histomorphologically difficult
      cases.

PMID- 11332079
TI  - Image cytometry in nonproliferative fibrocystic breast changes. Ploidy evaluation
      and epidemiologic study.
AB  - OBJECTIVE: To determine the usefulness of image cytometry on fine needle
      aspirates from patients with fibrocystic changes (FCCs) to assess the subsequent
      risk of breast cancer. STUDY DESIGN: Thirty-five hundred archival cases with fine
      needle aspiration (FNA) biopsy were assessed to select nonproliferative FCCs of
      the breast (500 cases), also classified as type 1 (FCC I). DNA evaluation was
      analyzed by means of image cytometry on ductal epithelial cells and on apocrine
      metaplastic cells; 97 quantifications were performed. Cytometric variables
      investigated were: DNA ploidy, G0/G1 peak of diploid nuclei, S-phase fraction,
      5cER, 2cDI and coefficient of variation. Two groups each with 15 years of follow
      up were formed: Simple pathology (SP), fibrocystic changes alone; associated
      pathology (AP), FCCs plus breast cancer. Each was studied separately and
      compared. RESULTS: In SP cases the average ploidy was 2.2 for epithelial cells
      and 4.2 for apocrine cells. The proportion of G0G1 diploid nuclei was 100%. In
      the study of AP, the average ploidy was 2.2 for epithelial ductal cells and 4.1
      for apocrine ones, for a slight increase in SPF. Ductal cells were diploid, while
      apocrine cells were tetraploid, with statistical significance of P < .05. For the
      epidemiologic study we calculated the proportion of patients with FCC I who
      developed cancer by referring to a historical cohort study, obtaining a relative
      risk of 0.7. CONCLUSION: Our results prove that DNA image cytometry applied on
      FNA cytology is a very useful, minimally invasive and reliable tool to determine
      higher activity and risk for development of breast cancer in FCC I and thus to
      establish the need for closer follow-up of these patients. In addition, apocrine
      metaplastic cells of the breast display a tetraploid DNA histogram, while the
      other karyometric variables remain in the range of normality.

PMID- 11332080
TI  - EGFR gene amplification in glioblastomas. Is there a relationship with morphology
      of tumor cell nuclei and proliferative activity?
AB  - OBJECTIVE: To confirm a relationship between histomorphology of glioblastomas and
      amplification of the gene for the epidermal growth factor receptor (EGFR) as the
      most important molecular biologic alteration in these tumors. STUDY DESIGN: In
      paraffin sections of surgical specimens from 71 primary resected glioblastomas,
      tumor cell nuclei in the region with the highest proliferative activity (Ki-67
      immunostaining) were investigated morphometrically. Shape variables (roundness
      factor, Fourier amplitudes) and nuclear area were measured. Additionally, the
      numerical density of Ki-67-positive tumor cell nuclei was estimated. Differential
      polymerase chain reaction (PCR) was performed from paraffin sections of the same
      tumor area. The signals for the EGFR gene and IFN gamma reference gene were
      quantified densitometrically. RESULTS: Cases with distinct EGFR gene
      amplification (EGFR/IFN ratios > 5) revealed significantly lower mean values for
      several Fourier amplitudes, indicating a more regular nuclear shape when compared
      with cases without evidence of EGFR gene amplification (EGFR/IFN-ratios < or =
      1). The Ki-67 index and nuclear area showed no significant differences between
      these groups. Although a large variation in nuclear morphology was observed for
      cases without evidence of EGFR gene amplification, discriminant analysis based on
      morphometric variables provided a good separation of these cases from cases with
      distinct EGFR gene amplification, with a high percentage of statistically correct
      reclassified cases. CONCLUSION: Our results provide evidence of a relationship
      between genetic alterations and histomorphology of glioblastomas.

PMID- 11332081
TI  - Nuclear chromatin patterns in normal, hyperplastic and atypical endometrium.
AB  - OBJECTIVE: To characterize the nuclei of endometrial lesions for the diagnostic
      categories of normal glandular tissue, simple hyperplasia, atypical hyperplasia
      and adenocarcinoma of the endometrium, with the specific goal of probing for
      heterogeneity. STUDY DESIGN: For each diagnostic category the images of 360
      nuclei were recorded on a high-resolution video microphotometer. Features
      descriptive of the statistical and spatial distribution of nuclear chromatin were
      computed for each nucleus. A nonsupervised learning algorithm, P-index, was
      employed to establish subsets of nuclei within each diagnostic category and to
      determine whether these subsets were statistically significantly different in the
      nuclear chromatin pattern. RESULTS: Lesions from cases of hyperplasia, atypical
      hyperplasia and adenocarcinoma of the endometrium each contained several subsets
      of nuclei with statistically significantly different chromatin patterns. For one
      such subset from each diagnostic category, a clear trend of progression toward
      adenocarcinoma could be demonstrated. CONCLUSION: The nuclei in endometrial
      lesions represent a highly heterogeneous set. Any measure of lesion progression
      or regression due to chemopreventive intervention, in an individual case, will
      have to examine the proportion of nuclei in each of these subsets as well as
      measures of deviation from normal for each subset.

PMID- 11332082
TI  - Early diagnosis of mesothelioma in serous effusions using AgNOR analysis.
AB  - OBJECTIVE: To compare the results of conventional cytology, DNA image cytometry,
      immunocytochemistry and argyrophilic nucleolar organizer region (AgNOR) analysis
      for the diagnosis of malignant cells in serous effusions. STUDY DESIGN: One
      hundred twenty effusions, 40 with carcinoses, 40 with malignant mesotheliomas and
      40 without tumor cells on follow-up were studied by conventional cytology and
      three adjunctive methods. RESULTS: Unequivocal tumor cells were detected in 92.5%
      of effusions due to carcinoses and in 45% due to mesotheliomas. Applying
      immunocytochemistry with BerEP-4 positivity and DNA image cytometry with
      aneuploidy as a marker revealed 100% of carcinoses and 71.7% of mesotheliomas.
      Applying the experimentally found thresholds of 2.5 AgNORs as "satellites" and
      4.5 AgNORs as "satellites and clusters" together as mean values per nucleus
      resulted in a 95% correct rate of mesothelioma and 100% rate of carcinoma cell
      identification without false positive diagnoses. CONCLUSION: AgNOR analysis may
      be a useful adjunct to other methods in the routine diagnosis of malignant serous
      effusions. It seems to be the most sensitive method in early cytologic diagnosis
      of mesotheliomas in effusions. Seventy-three percent of malignant mesotheliomas
      were diagnosed cytologically at first on effusions. Forty-seven percent of
      patients with malignant mesotheliomas were identified at the early tumor stage T1
      N0 M0.

PMID- 11332083
TI  - Correlation between angiogenesis, apoptosis and cell proliferation in invasive
      ductal carcinoma of the breast and their relation to tumor behavior.
AB  - OBJECTIVE: To investigate the relationship between angiogenesis, apoptosis and
      cell proliferation in invasive ductal carcinoma of the breast and their relation
      to tumor behavior. STUDY DESIGN: Microvessels were immunohistochemically labeled
      with antibody to CD34 in sections from 82 cases of invasive ductal carcinoma.
      Computerized image analysis was used to evaluate microvessel density (MVD). The
      authors measured the apoptotic index (AI) using the terminal deoxynucleotidyl
      transferase (TdT)-mediated dUTP nick-end labeling technique and proliferating
      cell nuclear antigen labeling index (PCNA LI) by PCNA immunohistochemistry on
      serial sections. RESULTS: Statistical analysis revealed a significant inverse
      correlation between MVD and AI (r = -.313, P = .004) and failed to find a
      significant correlation between MVD and PCNA LI. There was a significant positive
      correlation between AI and PCNA LI (r = .393, P = .000). Significant differences
      in AI between high MVD (> or = 59.9%) and low MVD (< 59.9%) were seen (P < .001),
      with no appreciable differences in PCNA LI between the two groups. Histologic
      grade and stage were the only independent prognostic factors in both disease-free
      and overall survival. CONCLUSION: Angiogenesis in breast cancer may be related to
      the ability of tumor cells to survive rather than to their proliferative
      activity. Apoptosis is related to cell proliferation in breast cancer.

PMID- 11332084
TI  - Adjusting interphase FISH results in epithelial tissue sections to whole cell
      complement.
AB  - OBJECTIVE: To derive an equation to compensate for the discrepancies between
      whole cell preparations and tissue sections for more accurate enumeration of
      fluorescence in situ hybridization (FISH) signals per cell. STUDY DESIGN: Mean
      centromere signal counts in touch preparations and corresponding 4-6-micron
      sections of paraffin-embedded tissue were calculated. Mean widest nuclear
      diameters were also determined from the tissue sections. The observed data were
      analyzed to define the volumetric relationships between tissue sections and whole
      cell preparations. RESULTS: Analysis of results from six lung specimens yielded
      an equation that approximates whole versus sectioned nuclear volume and permits
      accurate quantification of mean FISH signal count in histologic sections, as
      follows: [formula: see text].

PMID- 11332085
TI  - [The tissue engineering research on synovialization of non-synovial membrane
      tendon].
AB  - The synovial membrane tissue within the flexor digital tendon sheath of the
      rabbit's toes was cultured in vitro. The synovial cells suspension of the
      subculture was cultured with the segments of the non-synovial membrane tendon of
      the rabbit's toes. Under the light microscopy, scanning electronic microscopy and
      immunohistochemical examination, the result showed that the synovial cells
      crawled and covered the surface of the segments of the non-synovial membrane
      tendons. It is suggested that the non-synovial membrane tendon could transform
      into a synovial membrane tendon.

PMID- 11332086
TI  - [Research and development of standard (DICOM) interface for digital color
      ultrasound system].
AB  - In this paper, the authors, who have the experience in developing DICOM interface
      for a digital color Doppler ultrasound system, analyze the requirements for a
      digital ultrasound system DICOM interface, set forth it's design and
      implementation using object oriented and hierarchy method. Finally, conclusion is
      given.

PMID- 11332087
TI  - [Effects of TNF-alpha on IL-8 mRNA expression in endothelial cells].
AB  - As a kind of chemokine, IL-8 plays an important role in inflammatory reaction.
      Its expression in endothelial cells is regulated by a variety of cytokines. In
      this study, after incubating cultured human umbilical vein endothelial
      cells(HUVECs) with TNF-alpha for different time, we employed RT-PCR to assay IL-8
      mRNA expression and immunocytochemical staining to detect NF-kappa B activation
      in HUVECs. The results revealed: (1) IL-8 mRNA expressed little in untreated
      HUVECs; after HUVECs was pre-incubated with TNF-alpha for 1 hour, IL-8 mRNA
      expression increased greatly, and it increased further after pre-incubated for 3
      hours; however, when HUVECs was pre-incubated with TNF-alpha for 6 hours, IL-8
      mRNA expression decreased, and it almost decreased to basal level when pre
      incubated for 9 hours; (2) the immunoreactivity of NF-kappa B p65 in the nuclei
      of untreated HUVECs was negative; it became positive in the nuclei of HUVECs pre
      incubated with TNF-alpha for 1 hour and 3 hours; it became weak positive in the
      nuclei of HUVECs pre-incubated with TNF-alpha for 6 hours, and after 9 hours, pre
      incubation, the immunoreactivity of NF-kappa B p65 in the nuclei of HUVECs was
      negative. These results implied that TNF-alpha was capable of inducing IL-8 gene
      expression and activation NF-kappa B. and Their time courses were similar, thus
      suggesting that the induction of IL-8 gene expression by TNF-alpha is probably
      due to the activation of NF-kappa B.

PMID- 11332088
TI  - [A new method for lowering noise of ECG signal].
AB  - In this article, a new method is introduced to reduce the noise in ECG signal. We
      use accumulation-division method in frequency area, which can solve the problem
      of locating the initial position. This problem exists definitely in time area. By
      using this method, automation in disposing the noise can be realized. The result
      of this disposing is an integrated and low noise level cycle of ECG signal, which
      contains all useful characteristic signals. We hope it will be convenient for
      doctors.

PMID- 11332089
TI  - [The standard for electronic data exchange in healthcare environments--HL7].
AB  - With the development of HIS/RIS(Hospital/Radiology Information System), it is
      very important to study the HL7(Health Level Seven) Standard for electronic data
      exchange in healthcare environments. Firstly, in this paper, the history,
      development goal and conceptions of HL7 are introduced. Secondly, its
      applications and auto-realization technologies are presented. Then, the problems
      which exist in the standard and the difficulties of HL7 in China are analyzed.
      Finally, some helpful suggestions about the development of HL7 in China are
      proposed.

PMID- 11332090
TI  - [Progress in the study of biomimetic process for depositing apatite coatings].
AB  - The biomimetic method, which mimics the natural deposition of biologic apatite,
      has opened up a new way to develop biomaterials. This paper gives a brief
      introduction of various biomimetic methods to deposit apatite coatings, and the
      mechanical and biological properties of the coatings.

PMID- 11332091
TI  - [Applied researches on polylactide internal fixation devices].
AB  - Nowadays, more and more basic and clinical researches on polylactide internal
      fixators were carried out in China. In this paper are reviewed the researches of
      polylactide acid(PLA), including its physical and chemical characters,
      biodegradation, absorption and mechanical properties, effects on fracture
      healing, and clinical application. Some problems that have not been solved are
      high-lighted and discussed. Also dealt with are some researches of PLA in future.

PMID- 11332092
TI  - [Research on fibrotic effect of Ni-Ti and 317L alloys in esophagus].
AB  - This study was conducted to examiune the fibrotic effect of Ni-Ti and 317L alloys
      in esophagus. The extract fluid from Ni-Ti, 317L alloys was made according to the
      ASTM standards of U.S.A. The Fb of esophageal scar was cultured primarily, then
      incubated with alloy abstract fluid. The proliferating activity of Fb was
      measured by MTT at 4, 24, 48, 72 hours in the course of culturing. The esophagus
      embedding test of Ni-Ti, 317L alloys was made according to ASTM standards of
      U.S.A. The tissue around the alloys was taken at weeks 2 and 12, and the
      pathologic changes were analysed. The results showed that Ni-Ti, 317L extract
      could depress the proliferating function of Fb gently, and the depressing action
      increased gradually with the culturing time. The result of embedding test was in
      accord with the ASTM standards of U.S.A. completely; the fibrotic membrane around
      the NiTi, 317L alloys became thinner with embedding time. These findings
      suggested that the scattering composition of Ni-Ti, 317L in body fluid might not
      activate the proliferating and secreting function of Fb, and the two alloys could
      not lead to fibrosis of esophagus aroun them.

PMID- 11332093
TI  - [Progress in the studies on the evaluation of biocompatibility of biomaterials].
AB  - Biocompatibility remains the central theme for biomaterials applications in
      medicine. It generally refers to the compatibility between the biomaterials and
      the receptor, including tissue-compatibility and blood-compatibility. The
      definition of the biocompatibility has been greatly changed in recent years; it
      is now accepted as involving two principle areas, one is the principle of
      'biosafety', the second is the principle of 'biofunctionality'.

PMID- 11332094
TI  - [The research of receptor-mediated drug carrier].
AB  - One way to increase the concentration of drug in diseased tissue is to attach
      drug to a suitable carrier such as protein or peptides, which can improve the
      pharmacokinetic properties of drug and decrease it's side-effect on normal
      tissue. The developments of receptor-mediated transporting of drug assotiated
      with protein or peptides are reviewed in this paper. The most frequently used
      receptors and drug carriers and the bonds between the drug and the carrier are
      introduced. The machanism of transporting and the factors that affect the
      efficiency of the drug carrier are discussed as well.

PMID- 11332095
TI  - [Research advances of multidimensional reconstruction of ultrasonic heart
      images].
AB  - The methods, present research situation, existing problems, and application
      foreground of multidimensional reconstruction of ultrasonic heart images are
      discussed in the present paper. According to the procedure of multidimensional
      reconstruction of ultrasonic heart images, the discussions are presented in
      respect to image acquisition, processing, and display. Based on the present
      situation and existing problems, the future development and application
      foreground are proposed.

PMID- 11332096
TI  - [Application of time-frequency analysis on medical signal processing].
AB  - The frequency content of many biomedical signals can change rapidly with time.
      Conventional Fourier spectral analysis techniques are insufficient for analyzing
      the time-varying spectral content of these signals. By mapping a one-dimensional
      function of time(or frequency), the time-frequency representation can localize
      the signal energy in both the time and frequency directions. It has been shown
      that many biomedical signal problems may benefit from time-frequency analysis.
      The basic method of time-frequency analysis and its application in biomedical
      signals processing are introduced.

PMID- 11332097
TI  - [Review of filtering algorithms for medical ultrasonic images].
AB  - Several kinds of filters for medical ultrasonic images, such as multidimensional
      filter, adaptive weighted filter (for example, adaptive weighted median filter),
      adaptive window selecting filter (for example, homogeneous region growing mean
      filter and adaptive speckle suppression filter) and two-step filter, are
      introduced. The existing problems and the progress trend are also discussed. Some
      application instances for medical ultrasonic images of the filters discussed and
      the performance of the filters presented are based on the present authors'
      practice.

PMID- 11332098
TI  - [Edge-detection and its application in medical image processing].
AB  - Edge-detection is all the time a major problem in the computer early vision, and
      it plays an important role in image processing. This paper reviews classical and
      new methods of edge-detection and discusses its application in medical image
      processing.

PMID- 11332099
TI  - [Kinetics of in vitro drug release from chitosan and N-alkyl chitosan membranes].
AB  - By using the so-called "lag-time" method, we studied the effect of membrane
      thickness(h), initial drug concentration(Co) and flow rate(V) on the difusion
      coefficient(D) of model drug in membranes. The experiment indicates that D
      increases as h and v increase; D Keeps constant when C0 changes; Under the same
      condition, the D value of N-alkyl chitosan membrane is bigger than that of pure
      chitosan membrane.

PMID- 11332100
TI  - [Researches on high frequency inverter in X-ray machine].
AB  - This paper mainly explicates the high frequency inverter circuit and its features
      and deliberates the question of how to prevent the short circuit of inverter.

PMID- 11332101
TI  - [Establishment and application of a data management program for BY 960 ambulatory
      blood pressure monitoring system].
AB  - Report of ambulatory blood pressure monitoring may contain a large number of data
      which is very important for the clinical studies on subjects' blood pressure.
      Most of the ambulatory blood pressure monitoring systems in use at present are
      lacking in database managing function, which is very inconvenient to the research
      work. In accordance with the characteristics of BY 960 ambulatory blood pressure
      monitoring system (produced by Shenzhen NewEra Tech Co., Ltd.), a set of data
      management program was established. It can automatically transfer the ambulatory
      data to database sets and is confirmed to be a practical tool for the research
      work.

PMID- 11332102
TI  - [The numerical simulation of the dynamic stress field from impacting head].
AB  - In order to study the mechanism of impact injury to the head, we have simulated
      the development of the stress field by using the numerical simulation method. The
      process of the head having been impacted vertically by an impactor can be
      described as a 2D problem, and the reactions of the head subjected to impacted
      force can be simulated and analyzed by the method based on the finite difference
      method (FDM). The model is subjected to applied force by an impactor with the
      initial velocity of 25 m/s (90 km/h). The pre-processing for the model is done on
      the microcomputer software. Once imported to the software, the nodes and elements
      are generated and material characteristics are assigned. The results demonstrate
      that the high resolution computer graphics can provide the dynamic distribution
      of the stress field, which can clearly show how the stress is developed, and how
      many its value is. The results are helpful to understanding the mechanism of
      impact injury to head.

PMID- 11332103
TI  - [Preparation and quality control of cross-linked agarose coated activated
      charcoal (CAAC-II) used as adsorbents for hemoperfusion in artificial liver
      support].
AB  - The preparation and the quality control of cross-linked agarose coated activated
      (CAAC-II) were described. The crosslinking reagent epichlorohydrin was removed.
      Investigations indicate that the trace elements such as Pb, Cd, As, Cr, Fe and
      heavy metals, the pH, NH4+, SO4(2-), and ultraviolet absorbance in sample have
      met the requirements in Chinese Pharmacopeia and some other relevant standard
      promulgated by the Ministry of Health. No epichlorohydrin was detected in CAAC
      II.

PMID- 11332104
TI  - [A design of Hospital Information System].
AB  - This paper describes a design for Hospital Information System on the basis of
      local area networks.

PMID- 11332105
TI  - [The normalization creep functions of C5.6,T6.7,L4.5 interverbral discs of human
      vertebral column].
AB  - In this paper are reported the creep experimental studies on 9 fresh C5.6
      intervertebral discs,9 fresh T6.7 intervertebral discs and 10 L4.5 intervertebral
      discs that were taken from the bodies of ten men(aged 19-35 years) who had died
      of head injury 1-4 h before. By simulating the temperature of human body (36.5
      degrees C +/- 0.5 degree C) and putting 300 N load on the discs, we measured the
      intervertebral creep effects and obtained the strain-time curves.

PMID- 11332106
TI  - [Biomechanical studies on two thoracolumbar implants in cadaveric spine].
AB  - The aim of these studies was to evaluate the biomechanical characteristics of two
      devices and provide information for clinical choice. In vitro cadaveric spine
      testing which consisted of the stability test and the yield strength test was
      performed. In hemicorpectomy model, the AF was stiffer than the Kaneda in
      flexion, extension and left lateral bending (P < 0.01). In total corpectomy
      model, the AF was stiffer than the Kaneda in flexion, left lateral bending and
      axial rotation (P < 0.01). The average values of yield strength(M) for the
      Kaneda, the AF and the intact were 477.3 kg, 544.4 kg and 493.6 kg resectively.
      The stability of the AF is superior to that of the Kaneda. In total corpectomy,
      the Kaneda is significantly unstable in axial rotation. Both devices restore
      effectively load carrying capacity of the spine.

PMID- 11332107
TI  - [Effect of estrogen on hemodynamics and vascular remodeling with Takayasu
      arteritis].
AB  - This study utilized Takayasu arteritis (TA) model to do the experiment in order
      to observe the remodeling of arterial geometry. Plasma estrogen, progesterone and
      products of nitrous oxide (NO2- and NO3-) were examined. Qualitative analyses of
      maximum (MAX), minimum (MIN) and mean (MEAN) velocity of blood flow, resistant
      index (PI), pulsatile index (PI), and shear stress (SS) of abdominal aorta were
      performed. The results showed that plasma estrogen, progesterone and products of
      nitrous oxide were respectively 1137.80 +/- 189.30 pg.ml-1, 14.10 +/- 1.61
      micrograms.ml-1 and 195.78 +/- 53.01 mumol.L-1 in experiment group, whereas in
      control group, they were 34.74 +/- 10.20 pg.ml-1, 2.60 +/- 1.83 micrograms.ml-1
      and 12.16 +/- 3.28 mumol.L-1 respectively, P < 0.01. In comparison of hemodynamic
      parameters of abdominal aorta, the MAX and MIN of experiment group were
      profoundly higher than those of control group. SS increased markedly in
      experiment group. The observation of arterial remodeling in vitro found wall
      thickening. The thickness of abdominal aortic wall and inside diameter of vessel
      cavity ratio (h/Di) was 0.6145 +/- 0.1654 in experiment group and 0.2151 +/-
      0.0266 in control group, P < 0.01. The arterial collagen content in experimental
      group was significantly higher than that in control group. Hyperestrinemia gives
      rise to a series of hemodynamic alterations, influences vessel remodeling along
      with TA, and finally results in arterial stenosis, occlusion or aneurysms due to
      the constitutional composition of vascular wall reforming.

PMID- 11332108
TI  - [A 40 Hz event-related potential detecting system based on correlation-threshold
      method].
AB  - A 40 Hz event related potential(ERP) detecting system is introduced here. The
      system employs the elliptic--type filters which have excellent edge features to
      extract signals of narrow-band frequency. It exploits the correlation--threshold
      method proposed by us to cancel the muscle artifacts. We also realizes the
      automatic control of experiment procedure and statistical data processing in
      microcomputer.

PMID- 11332109
TI  - [The research and application of ultrasonic blood densitometer].
AB  - This paper presents an ultrasonic blood densitometer for dynamic measuring blood
      density. Compared with traditional blood densitometer, the ultrasonic blood
      densitometer has the advantages of high precision, fast response and little
      sample etc.

PMID- 11332110
TI  - [Dynamic ECG Review & Analysis Workstation].
AB  - The integrated management and remote application of dynamic ECG data is the
      future of the Holter System. This article introduces a kind of Dynamic ECG Review
      & Analysis Workstation that includes the function of integrated management and
      network. It has solved well the problems of common usage, archiving, total ECG
      analysis and remote transmission which exist in the traditional ECG Review &
      Analysis Systems.

PMID- 11332111
TI  - [A computer image processing system to analyze endothelial cell-platelet thrombus
      quantitatively].
AB  - A Computer Image Processing System for cone-plate rolling model which forms
      endothelial cell-platelet thrombus in vitro is presented in this paper. Some
      parameters such as endothelial cell shape parameters (area, perimeter, long axial
      length, short axial length, angle of orientation, and shape index), platelet
      adhesion coverage, platelet adhesion density, diffusivity and surface reactivity
      constant are measured during the reaction of endothelial cells and platelet under
      the fluid shear stress condition. The invitro thrombus model and the
      corresponding quantitative analysis system is useful in the studies on
      endothelial cells-platelets interaction and mechanism of thrombosis and
      atherosclerosis.

PMID- 11332112
TI  - [Study on abstracting method of high frequency components of ECG].
AB  - This paper presents a method to abstract high frequency components from ECG. A
      new signal averaging method based on vectorcardiographic loop matched alignment
      is proposed. It improves the crucial estimation of signal averaging and ensures
      that every one of the cardiographic signals participating in signal averaging
      comes from the same heart beat, so that each of three leads at least has uniform
      low pass filter effect. These conclusions have been confirmed by the analysis of
      ECG in clinical test.

PMID- 11332113
TI  - [Multi-resolution blending rendering of the medical structure].
AB  - This paper presents a new medical data visualization method called multi
      resolution blending rendering which has been developed for visualizing the large
      medical volume data sets. Different from those multi-resolution rendering methods
      which simplify the structures by polygon mesh optimization technique, the new
      method uses different resolution levels to represent different parts of a
      structure at the same time. So, it can preserve the integrality of the structure
      and emphasize the important part of the structure when simplifying the structure.
      The new method also takes advantage of the good qualities of the wavelet
      transform and constructs the multi-resolution blending model of the structure by
      orthogonal wavelet transform and transition operator. The experiment proves that
      our method can effectively simplify the model of the structure, enormously reduce
      the number of the triangle of the structure and speed up the structure rendering.
      It is especially suitable for interactive observations on a complex medical
      structure.

PMID- 11332114
TI  - [The sieving performance of a new polyethersulfone hollow fiber plasma
      fractionation membrane].
AB  - Plasma fractionation membrane is very important in double filtration
      plasmapheresis. We studied a new polyethersulfone hollow fiber membrane plasma
      fractionator and evaluated the effect of time, transmembrane pressure (TMP) and
      mean shear rate on the sieving coefficient (SC) during membrane plasma
      fractionation. The sieving coefficients of various proteins reached their maximum
      values at 40 min at the plasma flow rate QI = 30 ml/min and plasma filtrated flow
      rate QF = 20 ml/min. The QF increased with the increase of TMP, and the point of
      the intersection of the curve of the QF vs. TMP and the SC vs. TMP was regarded
      as the ideal condition for plasma fractionation. The plasma filtrated rate PFR =
      QF/QI = 0.6-0.7. The TMP changed with the change of the mean shear rate, and the
      mean shear rate had little effect on the SC. The data is of significance to the
      application of plasma fractionation membrane.

PMID- 11332115
TI  - [Extraction of MUAP from NEMG signal using self-organization competing NN].
AB  - The pattern classification of motor unit action potential (MUAP) of needle
      electrode electromyogram (NEMG) signal by means of self-organization competing
      Neural Network(NN) has been accomplished in this paper. The parameters and the
      power of excited white-noise of auto-regressive (AR) model are taken as the
      feature of MUAP. The results of simulated NEMG and real NEMG all show that this
      method of classification is very effective and correct, and thus it presents a
      new approach to the extraction of MUAP template in the study of decomposition of
      NEMG.

PMID- 11332116
TI  - [An ECG waves separation technique based on mathematical morphology].
AB  - An ECG waves separation technique based on mathematical morphology is suggested
      and discussed in this paper. Without detection of QRS complexes, the QRS
      complexes can be eliminated by series morphological operations. Then the start
      points and end points of P-wave and T-wave can be decided and the waves of ECG
      are separated qualitatively and quantitatively. The results of qualitative
      separations are rather satisfied and the SDs of quantitative separation results
      are not very large. Also, ECG signals are filtered and baseline is normalized by
      morphological method.

PMID- 11332117
TI  - [The method of instantaneous pulse detection based on hybrid wavelet transform].
AB  - In this paper, we discuss the relation between matched filter and wavelet
      transform(WT), and point out that wavelet transform is just the matched filter
      with changeable detection template. According to this idea, the method of signal
      detection based on hybrid wavelet transform (HWT) is proposed. HWT in this paper
      means that in WT decomposition and reconstruction, we use two different mother
      wavelets. One is used as a changeable template for the pulses detection and the
      other is used for the characteristic enhancement of detected pulse. This method
      has been applied to the interference pulse detection in EEG signal. The
      experiment result shows that HWT has the good property for instantaneous signal
      detection.

PMID- 11332118
TI  - [Effects of laminar shear stress on IL-8 mRNA expression in endothelial cells].
AB  - This study sought to demonstrate that IL-8 expression in endothelial cells is
      regulated by not only chemical factors but also mechanical factors. After
      pretreating cultured human umbilical vein endothelial cells (HUVECs) with shear
      stress for different periods of time, we employed RT-PCR to assay IL-8 mRNA
      expression and immunocytochemical staining to detect NF-kappa B activation in
      HUVECs. The results showed: 1. IL-8 mRNA expressed little in HUVECs untreated or
      pretreated with low laiminar shear stress for 0.5 h; IL-8 mRNA expression
      increased when HUVECs were pretreated with low laminar shear stress for 1 h, and
      it increased further when HUVECs were pretreated for 2 h; 2. The immunoreactivity
      of NF-kappa B p65 in the nuclei of HUVECs untreated or pretreated with low
      laminar shear stress for 0.5 h was negative, while it became weak positive in the
      nuclei of HUVECs pretreated with shear stress for 1 h and positive in the nuclei
      of HUVECs pretreated for 2 h. The findings implied that low laminar shear stress
      was capable of inducing IL-8 gene expression and activating NF-kappa B, which
      were both time-dependent. The induction of IL-8 gene expression by laminar shear
      stress is probably due to the activation of NF-kappa B. On these grounds we come
      to the conclusion that IL-8 expression induced in endothelial cells by low shear
      stress may play an important role in the genesis and development of both
      inflammation and arterioatherosclerosis.

PMID- 11332119
TI  - [Expression of human brain derived neurotrophic factor gene in E. coli].
AB  - The primers specific for the full-length BDNF coding sequence was designed and
      synthesized. The BDNF coding sequence was directly amplified from human genomic
      DNA by using PCR and inserted into vector pGEM-3Zf(+). The recombinant DNA was
      transformed into the host cells JM109 to obtain the positive clone pGEMBF18. The
      restriction enzyme analysis and DNA sequence detection confirmed that the
      inserted fragment of clone pGEMBF18 is the full-length BDNF coding sequence. The
      hBDNF DNA fragment was recovered from the clone pGEMBF18 and ligated with
      prokaryotic expression vector pGEX-5T to construct the recombinant expression
      plasmid p5TBF34. The E. coli JM109 transformed with p5TBF34 was induced with
      IPTG. A new protein band with apparent molecular weight 43 kDa was detected in
      the lysate of the transformed cell by using SDS-PAGE. The result of western
      hybridization showed that this fusion protein reacted specifically to the
      antibodies to human BDNF. The amount of the soluble fusion protein was about
      503.04 mg/L lysate, 7.53% of total bacterial soluble protein of transformed
      cells, estimated by absorbance scanning of SDS-PAGE and protein quantitation.

PMID- 11332120
TI  - [Changes in erythrocyte rheologic properties after mild burn injury].
AB  - The changes in erythrocyte deformability and osmotic fragility were studied with
      an animal model of mild burn injury. The results showed that after the burn
      injury there was a gradual decrease with time at first and then a recovery in
      erythrocyte deformability. Maximum deformation index [(DI)max], integration
      deformation index (IDI) and osmotic fragility of RBCs drawn just after burn were
      almost identical to those before burn injury. (DI)max and IDI significantly
      decreased at 1, 2 h but not at 4, 7 h when compared with those before burn
      injury, however, the RBCs were less deformable at 4, 7 h. Erythrocyte osmotic
      fragility significantly increased only at 4 h after burn injury when compared at
      the time points of 0, 1, 2, 4, 7 h after burn with that before burn injury. The
      results indicated that the lesion in (DI)max and IDI, and the increase in osmotic
      fragility might be only related to the body fluid factors in this animal model.
      The decrease in erythrocyte deformability and the increase in erythrocyte osmotic
      fragility did not synchronize, suggesting that the changes might come about not
      by the same mechanism.

PMID- 11332121
TI  - [Temperature distribution of tumor tissues irradiated by microwave].
AB  - This paper calculates the temperature distribution of the spherical tumor,
      applying the theory of electromagnetic scattering and the thermal conductivity of
      tissues (including normal tissues and tumor tissues). Our research work will be
      of some value in clinical medicine.

PMID- 11332122
TI  - [Study of noninvasive intracranial pressure monitoring by bioelectric impedance
      method].
AB  - The changes of intracranial components and corresponding brain impedance were
      analyzed while intracranial pressure was increasing, and the relation of
      intracranial pressure pulse wave and brain impedance pulse wave were discussed. A
      theory of noninvasive intracranial pressure monitoring by bioelectric impedance
      was put forward. The result of primary experiment suggested that the theory be
      feasible.

PMID- 11332123
TI  - [A permanent implantable pulsatile impeller heart with a specially devised needle
      bearing].
AB  - The author's implantable pulsatile impeller pump can assist the circulation of
      the calves for several months. The termination of the experiments was related to
      wear of the mechanical bearing, which resulted in vibration of the rotor and pump
      failure. It seemed as if the experiments could have lasted indefinitely if the
      bearing had not failed. To solve the problem of bearing wear, a specially devised
      rolling bearing was investigated and applied to the impeller pump. Its service
      life is more than 10 years due to the wear-proof roller made of ultra
      highmolecular weight polythene. This newly devised impeller heart promises to
      have long-term and permanent applications. Compared with the magnetic bearing,
      the rolling bearing has the advantages of simpler construction and control, no
      consumption of energy, and better reliability.

PMID- 11332124
TI  - [Study of in vitro cultured microencapsulated adrenal cortical tissues of rats].
AB  - In order to investigate the growth of in vitro cultured microencapsulated adrenal
      cortical tissues of rats, we produced the microcapsules by using sodium alginate,
      calcium chloride and poly-L-lysine, etc. The adrenal glands were taken out of 24
      rats, half of the adrenal glands were microencapsulated (capsule group) while the
      other half were left free (noncapsule group). After 36 hours' in vitro culture,
      the concentrations of aldosterone and cortisol in culture solution were measured
      by radioimmunoassay. The two groups continued to be cultured for 24 and 36 hours
      with ACTH stimulation. The concentrations of aldosterone and cortisol at 24 and
      36 hours were detected respectively. Parts of adrenal cortical tissues were
      observed under light microscope and electron microscope. The results showed that
      the concentrations of aldosterone and cortisol in the microencapsulated adrenal
      cortical tissues were significantly higher than those of noncapsule group (P <
      0.01). In the capsule group, the concentration of cortisol after 36 hours' ACTH
      stimulation was significantly higher than that before ACTH stimulation (P <
      0.01). After 24 and 36 hours' ACTH stimulation, the concentrations of aldosterone
      and cortisol were significantly higher in the capsule group than in the
      noncapsule group. In the noncapsule group, regardless of ACTH stimulation, no
      significant change was seen in the concentration of aldosterone and cortisol (P >
      0.05). The cellular structure of adrenal tissues remained intact under light
      microscopic and electron microscopic observations, and the cells remained alive
      well. These data suggest that in vitro cultured cells of microencapsulated
      adrenal cortical tissues remain alive well. Microcapsule has not influenced the
      secretory function of adrenal tissues. Microencapsulated tissues have a good
      response to ACTH stimulation.

PMID- 11332125
TI  - [Adaptive moving averaging based estimation of single event-related potentials].
AB  - Event-related potentials (ERP) is pertinent to medical research and clinical
      diagnosis. Estimation of single event-related potentials (sERP) is the objective
      of ERP processing. A new technique, adaptive moving averaging based method for
      estimation of sERP, is presented. After analysis of the properties of background
      noise by crossing zero, the window length of moving averaging is adaptively set
      according to the maximum width of the impulse noise for each recorded raw data.
      The experiments are made with real recorded data and the results demonstrate that
      the performance of sERP estimation is excellent. So the method proposed is
      suitable to sERP processing.

PMID- 11332126
TI  - [Evaluation of biocompatibility on titanium-zicornium alloy].
AB  - In this study, the general toxicity tests including cytotoxicity, haemolysis and
      oral mucous irratation of the Ti-Zr alloy were investigated. The results showed
      the level of cytotoxicity was grade 0, the haemolysis degree was 0.15% and no
      histomorphologic change was observed in the animals of Ti-Zr alloy groups. These
      data indicate that Ti-Zr alloy has good biocompatibility as a dental material.

PMID- 11332127
TI  - [Large-capacity expanded cytoline-induced killer cells and its cytotoxic
      activity].
AB  - This study was conducted to establish the large-capacity culture methd of
      cytokine-induced killer (CIK) cells for clinical therapy and assess its effect on
      the fuction of cell-mediated immunity following autologous CIK cells reinfusion.
      Autologus CIK cells were expanded in 1000 ml culture-bag and reinfused back. The
      MTT method was used to test the cytotoxic activity of CIK cells before and after
      reinfusion. The results showed that the total amount of autologous CIK cells
      reinfusion exceeded 1.6 x 10(10) with the use of the culture method of large
      capacity. The PBMNC from patients treated by CIK cells showed significant
      increase in cytotoxic activity, no side effects were observed, and therefore the
      large-capacity culture method of CIK cells is a simle and safe therapy for
      treating the minimum residue of diseases.

PMID- 11332128
TI  - [Effect of tissue factor pathway inhibitor on the adhesion of platelet onto
      polyethylene and polyvinylchloride membranes].
AB  - Tissue factor pathway inhibitor(TFPI) is the major inhibitor of the extrinsic
      pathway of the blood coagulation cascade. Our previous study showed that TFPI
      could obviously prolong the blood coagulation time on the surface of
      polyethelene(PE) and polyvinylchloride(PVC) membranes in vitro and decrease the
      generation of thrombus on Dacron membrane in vivo. In the present study, the
      effect of TFPI on the adhesion of platelet onto PE and PVC membranes was
      investigated. PE or PVC membrane was cut into small pieces and incubated in 96
      well culture plate with GST or GST-TFPI fusion protein at 4 degrees C over night.
      Freshly collected rabbit blood was mixed with 3.8% sodium citrate. Platelet-rich
      plasma was separated by centrifugation and then incubated with the treated
      membranes at 37 degrees C for 30 minutes. The membranes were then washed, fixed,
      and freeze-dehydrated Adhesion of platelet was observed through scanning
      electronic microscope. The result showed that GST-TFPI treatment significantly
      decreased the number of platelet adhered on the membrane when compared with the
      GST and control group, and it suggested that TFPI might have a great potential to
      be used as an anticoagulant for improving the hemocompatibility of biomaterials.

PMID- 11332129
TI  - [From the prevention to the annihilation of "unworthy life"].
AB  - Starting from race hygienic and eugenic ideas at the end of 19th and at the
      beginning of the 20th century the development and the execution of the
      "euthanasia of children" by the Nazis is described. Particularly the carrying out
      of the killing action is so-called "special children's departments" is dealt with
      in detail by the use of available investigations. Finally questions about the
      perpetrator profile and regarding the significance of ethical principles in child
      and adolescent psychiatry are raised.

PMID- 11332130
TI  - [Selection and destruction--treatment of "unworthy-to-live" children in the Third
      Reich and the role of child and adolescent psychiatry].
AB  - During the period of National Socialism in Germany, many "asocial", mentally
      retarded or disabled minors were persecuted. Several measures had been discussed
      theoretically before, but the National Socialists put the theoretical proposals
      into practice. As a result children and adolescents were separated, sterilized or
      killed. In concentration camps so-called "depraved" minors were selected to get
      special education. The object of this effort was to adapt minors to the ideology
      of national socialism. After passing the law to sterilize patients with
      "hereditary diseases" in 1933 about 375.000 people were sterilized unvoluntarily.
      In 1939 sterilizations came to an end except for adolescents at "high risk of
      reproduction". During the second world war more than 160.000 adult psychiatric
      patients were murdered. In addition to that, also a large number of disabled and
      mentally retarded minors were killed. This campaign was called child
      "euthanasia". Physicians tried to determine children's "value of life" by
      economic criteria. Children with negative ratings (i.e. inability to work or
      insufficient mental maturing) were killed by fasting "cures" or by barbiturates.
      Beyond that children were also used as research subjects. Their death was an
      accepted consequence. Physicians were also very interested in brain research.
      Finally, the relation to German child and adolescent psychiatry will be analysed.
      In the special political and social context of the Third Reich the German child
      and adolescent psychiatry became more significant. As a result of this the German
      association of child and adolescent psychiatry and allied professions was founded
      1940 in Vienna. On this conference, some speakers suggested to persecute
      "asocial" minors. This suggestion was realized consequently. Up to now, the role
      of the German child and adolescent psychiatry has not been thoroughly discussed.

PMID- 11332131
TI  - ["Euthanasia of children" during dictatorship of national socialism: "special
      children's department" Ansbach in Germany].
AB  - Focus of this paper is a description of "child euthanasia" during National
      Socialism 1939-1945 in the "specialized children's department" of the Ansbach
      state hospital. The historical and ideological bases for euthanasia and the
      development of child and adolescent psychiatry are explained. Material was found
      in public archives and trial records of German courts. 156 case histories of
      children who were killed in the Ansbach state hospital were evaluated. Child
      euthanasia in Ansbach was done in the same stereotyped way as in other
      specialized children's departments. The 156 children were aged between one week
      and 16 years. 39 children died within the first three months, 31 children died
      within three to six months in hospital. Most children were autopsied, at least 86
      brains were examined neuropathologically. The trials against the involved
      physicians were quashed finally in 1968.

PMID- 11332132
TI  - [National socialist "children's euthanasia" program in the province of Westphalia
      (1940-1945)].
AB  - As part of the organization structure of the "Reich committee for scientifically
      registering genetic and inherent serious illnesses" "childrens' special wards"
      were established in the province Westphalia in the child-psychiatry St.
      Johannesstift in Niedermarsberg (end of 1940), and then in the
      Provinzialheilanstalt Aplerbeck (end of 1941). The establishment thereof and
      personnel recruiting were done in close operation with provincial authorities. In
      Niedermarsberg external nurses were also employed. When the activities in the
      Marsberger ward became public despite efforts to keep them secret, the provincial
      association felt forced to establish a replacement ward in Dortmund-Aplerbeck.
      This ward was integrated stronger into the hospital-internal and regional care
      structures regarding personnel and institutional aspects than the previous ward.
      The actions of "child euthanasia" were based on a combination of hierarchical
      decision-making structures, limited responsibility, and scientific justification.
      The people performing these activities were provided action options withdrawal
      possibilities. For the affected parents the events were shifted into a
      psychological grey area which did not force decisions in principle. The internal
      conditions of the "childrens' special wards", the procedures and the "treatments"
      of the children were clearly regulated; the "euthanasia" activities themselves
      can be comprehended only in fragments from testimonies. By analyzing the
      reception books in connection with the medical files it is possible to make
      statements regarding the number of deaths, the death rate and cause, and also
      several social characteristics of the children. The fate of the children in the
      Westphalian "childrens' special wards" shows that the work in these regional
      "Reich committee wards" was limited to caring, observing, selecting and killing.
      The attempts of scientific justification are exposed as cover-ups.

PMID- 11332133
TI  - [Chairman of the German Society for Child Psychiatry and Educational Therapeutics
      in World War II].
AB  - Hans Heinze was one of the three experts on child euthanasia in the
      "Reichsausschuss zur wissenschaftlichen Erfassung erb- und anlagebedingter
      schwerer Leiden" and head of the first "Kinderfachabteilung" in Brandenburg
      Gorden, Germany. He was one of the experts in the euthanasia "Aktion T4". He
      became nominated president of the "Deutsche Gesellschaft fur Kinderpsychiatrie
      und Heilpadagogik" after Paul Schroder who died in 1941. The documents about his
      function exist in five German archives.

PMID- 11332134
TI  - Not all the holes are the same: USDA rules on Emmentaler.

PMID- 11332135
TI  - Alternative medicine or unproven methods?

PMID- 11332136
TI  - Errare humanum est, perseverare diabolicum.

PMID- 11332137
TI  - Deadly and toxic waste? Or intoxication by wastebasket papers?

PMID- 11332138
TI  - Matrix metalloproteinase inhibitors: how can we optimize their development?

PMID- 11332139
TI  - High-dose progestins for the treatment of cancer anorexia-cachexia syndrome: a
      systematic review of randomised clinical trials.
AB  - BACKGROUND: The aim of the present study was to summarise evidence from
      scientific studies on cancer anorexia-cachexia syndrome in order to assess and
      highlight the efficacy of high-dose progestins (megestrol acetate and
      medroxyprogesterone acetate) compared with placebo in patients with hormone
      independent tumors. MATERIALS AND METHODS: A systematic review of published
      randomised clinical trials was carried out by an extensive electronic and hand
      search through databases, relevant journals and books, congress, proceedings,
      reference lists, without any language or year of publication restriction. The
      research was conducted by two independent operators who collected the data in a
      form specifically designed for this review. Among the several possible outcomes,
      appetite and body weight were chosen. RESULTS: Fifteen randomised clinical trials
      (more than 2000 patients) were retrieved for the review. There was a
      statistically significant advantage for high-dose progestins as regards improved
      appetite: pooled odds ratio (OR) = 4.23, 95% confidence interval (CI): 2.53-7.04.
      Although the effect of high-dose progestins on body weight was less impressive,
      statistical significance was also reached for this outcome: pooled OR = 2.66, 95%
      CI: 1.80-3.92. Treatment morbidity was very low, due to the brief period of the
      treatment in most of the studies. CONCLUSIONS: The effects of high-dose
      progestins on appetite and body weight were clearly demonstrated. However,
      further studies are undoubtedly warranted to investigate other aspects of
      progestin activity, especially as regards dosage, duration and timing with best
      therapeutic index.

PMID- 11332140
TI  - The role of hormone replacement therapy in women with a previous diagnosis of
      breast cancer and a review of possible alternatives.
AB  - Estrogen replacement therapy either with (HRT) or without (ERT) accompanying
      progesterone is routinely offered to well women at the time of menopause, in
      order to relieve vasomotor symptoms, (hot flashes), reduce urogenital atrophy and
      reduce the risks of cardiovascular disease, osteoporosis and perhaps colon cancer
      and Alzheimer's disease. It is generally felt however, that women with a previous
      diagnosis of breast cancer are not suitable candidates for such therapy since
      either estrogen or progesterone may be associated with an increased risk of
      cancer recurrence. There are however, a variety of approaches to menopausal
      therapy in such women. A careful history must first be taken in order to identify
      the symptoms or conditions of concern. Vasomotor symptoms can be reduced by the
      use of other medications such as the antidepressant venlafaxine (Effexor).
      Estring, a vaginal estrogen ring can be used to reduce genitourinary symptoms,
      with little systemic estrogen absorption. Osteoporosis can be prevented or
      treated with calcium supplements, exercise, improved diet, bisphosphonates and/or
      selective estrogen receptor modulators (SERMs) while cardiovascular risk can be
      reduced by diet and exercise, as well as the appropriate use of lipid lowering
      and antihypertensive medications.

PMID- 11332141
TI  - Clinical impact of histologic subtypes in localized non-anaplastic nephroblastoma
      treated according to the trial and study SIOP-9/GPOH.
AB  - BACKGROUND: Histologic subtypes of standard histology Wilms' tumor (WT) and the
      effect of preoperative therapy on their clinical and histologic features, deserve
      to be analysed in respect to outcome to find an adequate baseline for therapy.
      PATIENTS AND METHODS: The German Society of Paediatric Oncology & Haematology
      enrolled patients from January 1989 to March 1994 for therapy according the
      International Society of Paediatric Oncology trial & study 9. Standardised
      preoperative therapy with dactinomycin and vincristine for 4-8 weeks was
      generally applied in patients between 0.5 and 16 years with localized renal
      tumors and imaging typical for WT. In 99.5% of cases representative material was
      sent for review to the Kiel Paediatric Tumour Registry. For prospective subtyping
      of 329 WT (258 after preoperative therapy, 71 with immediate surgery) modified
      Beckwith & Palmer criteria were used. Reduction in volume measured by imaging
      prior to chemotherapy and surgery was used to assess response (poor response:
      reduction < 40%; good response: reduction > or = 40%). RESULTS: There were 39% of
      patients treated with immediate surgery and 12.4% of patients with preoperative
      therapy in the age group up to 12 months. The difference in age (P = 0.022) was
      linked with different amounts of epithelial WT (15.5% vs. 3.1%), median age: 0.58
      and 0.93 years. Due to the effect of chemotherapy the amount of other WT changed:
      stromal 0% to 14%, mixed 45.1% to 29.4%, blastemal 39.4% to 9.3%). After
      preoperative therapy 37.6% of WT were predominantly regressive, 6.6% completely
      necrotic. Poor response was frequent in differentiated WT (86% of stromal, 75% of
      epithelial WT) but none relapsed. In the other WT with viable tumor left after
      preoperative therapy > 70% had good response, poor response was a risk factor (P
      = 0.0057). CONCLUSIONS: Subtyping according modified Beckwith & Palmer can be
      used in WT after preoperative therapy to stratify postoperative therapy in
      future. A milder therapy could be tested in differentiated WT at low stages and
      an intensified in the others with viable tumor left and poor response, i.e.,
      mainly blastemal WT.

PMID- 11332142
TI  - Phase II study of weekly 24-hour intra-arterial high-dose infusion of 5
      fluorouracil and folinic acid for liver metastases from colorectal carcinomas.
AB  - BACKGROUND: A multicenter phase II trial was initiated in order to evaluate the
      weekly, high-dose 24-hour infusion of 5-fluorouracil (5-FU) plus folinic acid
      (FA) in patients with unresectable colorectal cancer hepatic metastases. PATIENTS
      AND METHODS: A weekly hepatic arterial infusion (HAI) of FA 500 mg/m2 followed by
      a 24-hour infusion of 5-FU 2,600 mg/m2 (later reduced to 2,200 mg/m2) was given
      via a surgically implanted intra-arterial port system. One treatment cycle
      consisted of six weekly applications followed by a two-week rest period. Toxicity
      was assessed according to the WHO criteria. Chemotherapy was continued until
      disease progression or complete response occurred. RESULTS: A total of 50
      patients (40 chemonaive, 10 pre-treated) entered this trial. An objective tumor
      response occurred in 28 patients (56%), while 13 patients (26%) had stable
      disease. The median progression free survival was 12 months, and the median
      survival 22.3 months. Due to a high rate of gastrointestinal side-effects in the
      initial phase of the trial, the dosage of 5-FU was reduced to 2,200 mg/m2 for all
      subsequent patients. Diarrhea and nausea led to a dose reduction in 40% of
      applications and 24% of patients, respectively. One patient died of cardiac
      insufficiency unrelated to chemotherapy before response evaluation. CONCLUSIONS:
      This HAI approach using high-dose 5-FU was relatively well tolerated when 2,200
      mg/m2 instead of 2,600 mg/m2 was used. The activity of this regimen is promising
      and warrants further evaluation and modification.

PMID- 11332143
TI  - Changing socioeconomic correlates for cancers of the upper digestive tract.
AB  - BACKGROUND: Cancers of the upper digestive tract have long been associated with
      low socio-economic levels. It has however been suggested that in recent times the
      social gradient for these cancers is leveling off. PATIENTS AND METHODS: Data
      from three case-control studies on oral, pharyngeal and oesophageal cancer
      conducted in Northern Italy during the periods 1984-1992 and 1992-1997 were
      combined and re-analyzed. Cases were subjects admitted to the major teaching and
      general hospitals in the areas under study with incident, histologically
      confirmed cancer of the oral cavity and pharynx (n = 1126) and oesophagus (n =
      714). Controls were subjects admitted to the same hospitals for a wide spectrum
      of acute, non-neoplastic conditions, not related to smoking or alcohol
      consumption (n = 4642). RESULTS: In the 1980s a significant association was
      observed with low education and social class level. The multivariate odds ratios
      for oral, pharyngeal and oesophageal cancers combined was 1.78 for the lowest
      versus the highest educational level, and 1.75 for the lowest versus the highest
      social class. No consistent pattern of risk was observed with any of the socio
      economic indicators considered in the studies conducted in the 1990s.
      CONCLUSIONS: The present study indicates that the socio-economic correlates of
      cancers of the upper digestive tract have changed over the last few years in
      Italy, with a disappearance of the social gradient.

PMID- 11332144
TI  - Leanness as early marker of cancer of the oral cavity and pharynx.
AB  - BACKGROUND: It is not clear whether the purported association of leanness with
      cancer of the oral cavity and pharynx was due to cancer-related weight loss or to
      the influence of factors associated with leanness. PATIENTS AND METHODS: Seven
      hundred fifty-four incident cases of cancers of the oral cavity and pharynx and
      1775 controls, admitted to hospital for acute, non-neoplastic diseases, in Italy
      and Switzerland. Questionnaire included height, lifetime history of weight and of
      physical activity, waist and hip measurements, and a validated food-frequency
      section. RESULTS: Leanness at diagnosis was associated with elevated risk in men
      (adjusted odds ratio, OR for 5-unit decrease in body-mass index, BMI = 1.9; 95%
      confidence interval (CI): 1.6-2.2 in men). Male cases were significantly leaner
      than control subjects at the age of 30 and of 50. Thinner women also had an
      increased risk, but the inverse association with BMI was non linear. In both
      sexes, the association with leanness was restricted to smokers and moderate/heavy
      drinkers, but was not accounted for by drinking and smoking habits, nor by
      differences in physical activity or dietary habits. CONCLUSIONS: Leanness appears
      to be an early marker of some unknown biological effect of smoking and/or of
      alcohol abuse, which may contribute to the prediction of cancers of the oral
      cavity and pharynx. Cessation of smoking and substantial reduction of alcohol
      intake may improve nutritional status, besides stopping carcinogen exposure.

PMID- 11332145
TI  - Reproductive and hormonal factors and ovarian cancer.
AB  - BACKGROUND: Menstrual, reproductive and hormonal factors have been related to
      ovarian cancer risk, but further quantification of their role in various
      populations is required. PATIENTS AND METHODS: Cases were 1031 women, below age
      79, with incident, histologically confirmed epithelial ovarian cancer, and
      controls 2411 women, admitted between 1992 and 1999 to a network of hospitals in
      4 Italian areas for acute, non-neoplastic, diseases. Odds ratios (OR) were
      obtained using multiple logistic regression. RESULTS: Multiparity was associated
      with a significant reduction in risk of ovarian cancer (OR = 0.6 for 3, and 0.5
      for > or = 4 births). No consistent association was observed with time since
      first or last birth, nor with spontaneous or induced abortions. Late age at
      menarche (OR = 0.8), and early menopause (OR = 0.6) were inversely related to
      risk, as did long-term oral contraceptive use (OR = 0.5, for > or = 5 years).
      Hormone replacement therapy in menopause was associated with a non-significantly
      elevated risk (OR = 1.4). The pattern of risk was similar for women with and for
      those without family history of breast or ovarian cancer. CONCLUSIONS: This
      uniquely large study confirms and further quantities the relation between
      hormonal and reproductive factors and ovarian cancer. The pattern of risk
      observed cannot be totally explained by a role of ovulation in ovarian
      carcinogenesis.

PMID- 11332146
TI  - Sequential induction chemotherapy and concomitant chemoradiotherapy in the
      management of locoregionally advanced laryngeal cancer.
AB  - PURPOSE: To determine overall survival, progression-free survival, rate of voice
      preservation, and patterns of failure in locoregionally advanced laryngeal cancer
      treated with induction chemotherapy with or without surgery followed by
      concomitant chemoradiation. BACKGROUND: Locoregionally advanced laryngeal cancer
      has been conventionally treated with either surgery and adjuvant radiotherapy or
      radiotherapy alone, and clinical and functional outcomes have been poor.
      Chemoradiotherapy has been demonstrated to improve functional outcome and disease
      control over conventional treatment in recent randomized head and neck trials.
      PATIENTS AND METHODS: Advanced head and neck cancer patients were enrolled onto
      two consecutive phase II studies. Induction treatment consisted of three cycles
      of cisplatin, 5-fluorouracil (5-FU), leucovorin, and interferon-alpha 2b (PFL
      IFN) followed by surgery for residual disease. Surgical intent was to spare the
      larynx when possible. All patients then proceeded to concomitant chemoradiation
      consisting of seven or eight cycles of 5-FU, hydroxyurea, and a planned total
      radiotherapy dose of 7000 cGy (FHX). RESULTS: A subset of thirty-two laryngeal
      cancer patients with predominantly stage IV disease comprises the study group for
      this report. Clinical CR was observed in 59% of patients following induction
      therapy. The median follow-up was 63.0 months for surviving patients and 44.5
      months for all patients. At five years, overall survival is 47%, progression-free
      survival is 78%, and locoregional control is 78%. No distant failures were
      observed. Voice preservation with disease control was 75% at five years. Only two
      total laryngectomies were performed during the course of treatment and follow-up.
      Treatment-related toxicity accounted for two deaths. CONCLUSIONS: The addition of
      concomitant chemoradiotherapy to induction chemotherapy for locoregionally
      advanced laryngeal cancer appears to increase locoregional control and survival
      rates. PFL-IFN-FHX resulted in high rates of disease cure and voice preservation
      in a group of patients that has traditionally fared poorly in both clinical and
      functional outcome.

PMID- 11332147
TI  - CHOP followed by involved field radiation: is it optimal for localized nasal
      natural killer/T-cell lymphoma?
AB  - The present study aimed to analyse the treatment outcome of four cycles of CHOP
      (cyclophosphamide-vincristine-doxorubicin-prednisolone) followed by involved
      field radiation therapy (IF RT) for the treatment of stage I-II nasal natural
      killer (NK)/T-cell lymphoma. From March 1995 to December 1999, 17 patients
      (median age 41 years; range 30-66) with localized nasal NK/T-cell lymphoma were
      enrolled. B symptoms were noted in five patients (31%). Sixteen of seventeen
      patients (94%) were of low risk when classified according to the International
      Prognostic Index (IPI). The treatment plan consisted of four cycles of CHOP
      chemotherapy followed by IF RT of 45 Gy. Two patients received radiation during
      the first or second cycle of CHOP because of bleeding from the primary tumour
      site. Both patients achieved complete responses (CRs). In the remaining 15
      patients, after 4 cycles of CHOP, 6 CRs and 3 partial responses (PRs) were
      achieved (53% of response rate). IF RT was given to six patients (four in CR, one
      in PR and one in PD), and all six patients achieved CR. Overall, CR was achieved
      in 10 of 17 patients (58%). The planned sequential chemoradiotherapy was
      completed in only 6 of 17 patients (35%) because of the progression during
      chemotherapy. None of the patients who achieved CR experienced relapse of
      lymphoma during follow-up. The estimated overall three-year survival rate was
      59%. In univariate analysis, B symptoms and stage were significant prognostic
      factors for response and overall survival (P < 0.05). The present study suggests
      that four cycles of CHOP followed by IF RT is not satisfactory for treating
      patients with localized nasal NK/T-cell lymphoma, and that further exploration
      for improved therapy is needed.

PMID- 11332148
TI  - High incidence of central nervous system involvement in patients with metastatic
      or locally advanced breast cancer treated with epirubicin and docetaxel.
AB  - BACKGROUND: Clinically overt central nervous system (CNS) involvement occurs in
      10%-15% of patients with advanced breast cancer. PATIENTS AND METHODS: The
      International Breast Cancer Study Group (IBCSG) conducted a dose-finding phase I
      trial of epirubicin (E) and docetaxel (D) as first-line therapy in advanced
      breast cancer patients. The study was expanded into a phase II at the recommended
      doses of E 90 mg/m2 and D 75 mg/m2 every three weeks. From July 1996 to May 1998,
      a total of 92 patients (median age 50 years) entered the two studies. RESULTS:
      Twenty-eight out of ninety-two patients treated with the combination of E and D
      (30%) developed CNS metastases (95% confidence limits, 26%-35%), which were
      cerebral in twenty-five patients, leptomeningeal in two, and both in one. Of
      these 28 patients, 19 (68%) had an objective response. Median time for the
      development of CNS metastases from the start of chemotherapy was 15 months (range
      5-42), if excluding the 6 patients presenting CNS progression within 3 months
      from start of treatment. It is notable that 11 patients (39%) had progression in
      the CNS only. Median survival from appearance of brain metastases in the whole
      group was only three months (range 1-22). C-erbB-2 overexpression was found in 14
      out of 16 patients (87%) in whom the assay was performed (3+ in 10, 2+ in 1 and
      1+ in 3 cases). CONCLUSIONS: As anthracycline- and taxane-containing regimens are
      increasingly used both in the metastatic and in the adjuvant setting, a careful
      monitoring of any neurological symptom is advisable. Our preliminary observation
      on the possible increase of incidence of CNS involvement in patients with
      advanced breast cancer receiving this effective drug combination requires further
      evaluation.

PMID- 11332149
TI  - A phase I study of a fixed dose of cisplatin with increasing doses of raltitrexed
      (Tomudex) in the treatment of patients with locally advanced or metastatic
      squamous cell carcinoma of the head and neck.
AB  - PURPOSE: A phase I trial of raltitrexed in combination with cisplatin in patients
      with locally advanced or metastatic squamous cell carcinoma of the head and neck
      (SCCHN). PATIENTS AND METHODS: Eligible patients had locally advanced or
      metastatic SCCHN. Cohorts of patients were treated with escalating doses of
      raltitrexed (2.0 mg/m2 to 3.5 mg/m2) as a 15-minute intravenous infusion
      immediately followed by cisplatin (80 mg/m2) administered over four hours every
      three weeks to determine the maximum tolerated dose (MTD). RESULTS: A total of 17
      patients was administered 60 courses of an escalating dose of raltitrexed.
      Starting dose of cisplatin was initially 100 mg/m2 in the first three patients
      treated at the first dose level. Due to cisplatin-induced nephrotoxicity
      expressed as a creatinine clearance decrease by more than 50%, the cisplatin dose
      was reduced to 80 mg/m2 for all subsequent treatment cycles. Dose-limiting
      toxicity was observed at raltitrexed dose of 3.5 mg/m2 in two out of five
      patients. Dose-limiting grade 4 (CTC) neutropenia, grade 4 diarrhoea, grade 3
      lethargy and elevation of transaminases and bilirubine was seen in these two
      patients. One patient treated at the level of the MTD, died 23 days after the
      first cycle with unresolved gastro-intestinal toxicity. In all other dose levels
      toxicity was very limited. The recommended dose for further study was raltitrexed
      3.0 mg/m2 in combination with cisplatin 80 mg/m2. In 15 evaluable patients, we
      observed 9 WHO objective responses (1 complete and 8 partial). At the recommended
      dose level 3 partial responses were observed in five evaluable patients.
      CONCLUSION: The regimen of raltitrexed 3.0 mg/m2 followed by cisplatin 80 mg/m2
      on day 1, every three weeks has manageable toxicity and these doses are
      recommended for phase II evaluation. Results indicate that this combination is
      active for the treatment of patients with locally advanced or metastatic SCCHN.
      Recently, a phase II study has been started.

PMID- 11332150
TI  - Hearing the bad news of a cancer diagnosis: the Australian melanoma patient's
      perspective.
AB  - BACKGROUND: In the past, recommendations on how to break the bad news of a cancer
      diagnosis have been based on expert opinion. Recently, consensus-based guidelines
      for medical practitioners have been developed. The objective of this work is to
      investigate patient preferences for communication practices and to identify any
      disparities between these guidelines, patient preferences and patient
      recollections of hearing their diagnosis. PATIENTS AND METHODS: A consecutive
      sample of 131 newly diagnosed melanoma patients were surveyed approximately 4
      months after initial diagnosis to document their preferences and recollections of
      their communication experiences. RESULTS: Of the 'breaking bad news'
      recommendations investigated, patients did not strongly endorse the doctor
      helping tell others of the diagnosis or telling the patient about cancer support
      services. Very few patients expressed a preference for having another health
      professional present. One communication feature, the patient feeling confident
      about getting the best treatment, was endorsed as 'very important' but does not
      feature in published guidelines. The most notable disparities between guidelines
      and the reported experiences of patients related to perceived delays in receiving
      the diagnosis, and having adequate opportunity to ask their clinician questions.
      CONCLUSION: Current Australian recommendations on how to communicate a diagnosis
      of cancer were generally supported by the patients' expressed preferences, but
      several modifications are proposed. IMPLICATIONS: Suggestions are offered to help
      overcome the disparities identified between recommendations and patients'
      preferences when a diagnosis of cancer is being communicated.

PMID- 11332151
TI  - Impact of chemotherapy dose-density on radiotherapy dose-intensity after breast
      conserving surgery.
AB  - PURPOSE: To evaluate if chemotherapy (CT) dose-intensification jeopardizes
      radiotherapy (RT) dose-intensity (DI). PATIENTS AND METHODS: From 1992 to 1997,
      247 stage I-II breast cancer patients, treated with conserving surgery, were
      treated at the National Cancer Institute of Genoa in a randomized study comparing
      the same CEF regimen delivered every two weeks (CEF14) or three weeks (CEF21). RT
      was applied to the residual breast at a total dose of 50 Gy in five weeks.
      Allowance was made for treatment at 2.3 Gy per fraction in order to compensate
      for gaps (hypofractionation). Radiotherapy DI was expressed as the average total
      dose received each week, i.e., 'weekly dose-rate' (WDR). The effect of various
      tumour, treatment and patient-related factors on the endpoint (a delivered WDR of
      RT < 9.5 Gy) was investigated by univariate analysis. Factors found to have P
      value < or = 0.20 were entered in multivariate analysis. RESULTS: All but three
      patients (244 of 247, 98.8%) received a cumulative total dose of RT within +/-
      10% of that planned. Moreover, most of them (197 of 247, 79.8%) received an
      average WDR of > or = 9.5 Gy/wk. With univariate analysis the probability of WDR
      < 9.5 Gy/wk significantly correlated with age, menopausal status, concomitant
      administration of RT and CT, and white blood cell toxicity. Moreover, a positive
      effect on WDR was found in patients treated at 2.3 Gy per fraction. The type of
      treatment (CEF14 vs. CEF21) did not affect the probability of WDR < 9.5 Gy/wk.
      With multivariate analysis, age (< or = 55 vs. > 55 years, RR = 3.99, 95% CI:
      1.89-8.42, P = 0.0003), RT fractionation (conventional vs. hypofractionation, RR
      = 0.32, 95% CI: 0.15-0.68, P = 0.017) and WBC toxicity (none vs. some, RR = 1.54,
      95% CI: 1.06-2.22, P = 0.027) were independent predictors of WDR < 9.5 Gy.
      Regarding the CT-RT overlap, patients receiving more than two cycles of
      chemotherapy during radiotherapy had an increased risk of RT delay compared to
      other patients (RR = 3.74, 95% CI: 1.44-9.48, P = 0.0063). CONCLUSIONS: There is
      no evidence of a direct effect of CT dose-density on dose-intensity of RT.
      However, the concomitant use of CT and RT reduces the possibility of giving a
      full dose-intensity of RT.

PMID- 11332152
TI  - Treatment based on a combination of the CYP2B1/cyclophosphamide system and p53
      delivery enhances tumour regression in human pancreatic cancer.
AB  - BACKGROUND: Strategies based on the introduction of pro-drug activating enzymes
      or the restoration of tumour suppressor genes have been proposed as encouraging
      methods to improve the efficiency of treatments in pancreatic cancer. The in situ
      bioactivation of cyclophosphamide by cytochrome p450-2B1 and subsequent p53
      delivery were examined. MATERIALS AND METHODS: NP-18 cell line derived from a
      human pancreatic adenocarcinoma was treated in vitro with a combination of the
      Adenovirus-CYP2B1/cyclophosphamide and adenoviral-mediated wt-p53 reintroduction.
      Cell viability and cytometric cell cycle profiles were analyzed to evaluate the
      sensitivity of NP-18 cells to this treatment. The efficiency of this combination
      was assessed in an in vivo model consisting of xenografts into the subcutaneous
      tissue of Balb/c mice by tumour growth, histological analysis and cell cycle
      determinations. RESULTS: Ad-CYP2B1/cyclophosphamide or Ad-p53 treatments led to a
      marked decrease in cell viability of NP-18 cells. Combination of both treatments
      elicited a higher loss of cell viability and marked increases in sub-G1
      population in cell cycle profiles. Animals treated with the combination strategy
      showed a quick reduction of tumour volumes due to the bioactivation of
      cyclophosphamide by CYP2B1 and sustained growth inhibition throughout the period
      evaluated after p53 delivery. Only this group of animals presented statistically
      significant differences with respect to control and cyclophosphamide-treated
      groups (P < 0.05). CONCLUSIONS: These results indicate that in situ bioactivation
      of cyclophosphamide by CYP2B1 and the recognition of the damaged DNA by p53
      increase tumour regressions and may be a promising therapy for solid tumour
      therapy in man.

PMID- 11332154
TI  - High-dose radiation therapy and neoadjuvant plus concomitant chemotherapy with 5
      fluorouracil and cisplatin in patients with locally advanced squamous-cell anal
      canal cancer: final results of a phase II study.
AB  - PURPOSE: To analyse toxicity and response to a new scheme of neoadjuvant
      chemotherapy (CT) and concomitant radiochemotherapy (RT-CT) for locally advanced
      anal canal squamous-cell carcinoma (ACC). PATIENTS AND METHODS: Eighty patients
      with an ACC > 40 mm and/or with lymph node involvement were included (1 T1, 52
      T2, 14 T3, 13 T4, 18 N0, 30 N1, 32 N2-N3). Two cycles of 5-fluorouracil (5-FU)
      and CDDP were delivered as neoadjuvant CT and two during RT-CT. Pelvic (+/-
      inguinal) RT delivered 45 Gy in 25 fractions of 1.8 Gy. Involved fields were
      boosted after a one to two month gap (15-20 Gy). The median follow-up was 29
      months. RESULTS: One patient died of a pulmonary embolism on day 4. All patients
      received the entire treatment, with reduced 5-FU doses in 27% of the cases
      because of acute toxicity. Sixty-four grade 3 and five grade 4 toxicities were
      observed. No toxic death occurred. Complete response (CR) and partial response
      (PR) rates were, respectively, 10% and 51% after neoadjuvant CT, 67% and 28%
      after RT-CT and 93% and 5% after treatment completion (including 4 abdomino
      perineal resections). The three-year actuarial overall, tumour-specific,
      colostomy-free, relapse-free, disease-free and event-free survivals were 86%,
      88%, 73%, 70%, 67% and 63%, respectively. CONCLUSIONS: Tolerance was good. After
      neoadjuvant CT, most of the patients were objective responders. After treatment
      completion, all but five achieved CR. The long-term results confirm the
      durability of local control and low toxicity on the sphincter. An ongoing phase
      III intergroup trial analyses the impact of neoadjuvant CT, and the benefit of a
      high-dose boost irradiation, on local control and colostomy-free survival.

PMID- 11332153
TI  - Phase I study of the matrix metalloproteinase inhibitor, BAY 12-9566.
AB  - BACKGROUND: Matrix metalloproteinases (MMPs) are involved in tumor invasion and
      metastasis and have been implicated in breast, ovarian, colorectal, and lung
      cancer growth. We undertook a phase I study of BAY 12-9566, an inhibitor of MMP
      2, MMP-9, and MMP-3, in patients with solid tumors to determine its safety,
      pharmacokinetics, and effects on potential surrogate markers of biologic
      activity. PATIENTS AND METHODS: BAY 12-9566 was orally administered daily at four
      dose levels; 400 mg daily, 400 mg b.i.d., 400 mg t.i.d., and 800 mg b.i.d. Drug
      disposition was determined on days 1 and 29 with weekly trough levels measured
      during the first four weeks. Plasma vascular endothelial growth factor (VEGF),
      basic fibroblast growth factor (bFGF), and urinary pyridinoline and
      deoxypyridinoline crosslinks were determined at baseline, once weekly for four
      weeks, and then every four weeks. RESULTS: Thirteen patients were entered on
      trial. BAY 12-9566 was well tolerated, with only one grade 3 headache, one grade
      3 anemia, one grade 3 thrombocytopenia, and no musculoskeletal effects. The
      median treatment duration was 57 days (range 7-560). Mean trough levels of BAY 12
      9566 on day 28 ranged from 80.5 to 108.6 mg/l. Plasma trough levels were 1500
      42,000-fold above the Ki's for MMP-2, MMP-3, and MMP-9 at the 800 mg p.o. b.i.d.
      dose level. There was no significant change in VEGF, bFGF, pyridinoline, and
      deoxypyridinoline crosslinks with BAY 12-9566 administration. CONCLUSIONS: The
      recommended dose for further testing is 800 mg p.o. b.i.d.

PMID- 11332155
TI  - Dexrazoxane is a potent and specific inhibitor of anthracycline induced
      subcutaneous lesions in mice.
AB  - BACKGROUND: Recently, we have shown that dexrazoxane (ICRF-187) is an effective
      antidote against accidental extravasation of anthracyclines. Thus, it inhibits
      the lesions induced by subcutaneous (s.c.) daunorubicin, idarubicin, and
      doxorubicin in mice and has proven to be successful clinically as well.
      Dexrazoxane is a potent metal ion chelator as well as being a catalytic inhibitor
      of DNA topoisomerase II. However, the mechanism behind the protection against
      anthracycline extravasation is not known. MATERIALS AND METHODS: Mice were
      injected s.c. with daunorubicin or doxorubicin. Systemic N-acetylcysteine, alfa
      tocoferol, amifostine, merbarone, aclarubicin, ADR-925, and EDTA were
      administered i.p. immediately hereafter or as a triple-treatment over six hours.
      Intralesional (i.l.) adjuvants were injected immediately after and into the same
      area as the anthracycline. The frequency, duration, and sizes of wounds were
      observed until complete healing of all wounds. RESULTS: Triple-treatment with
      systemic dexrazoxane was superior to single dosage and completely prevented
      lesions after s.c. daunorubicin and doxorubicin. Low-dose i.l. dexrazoxane was
      effective in protecting as well. In contrast, none of the other seven adjuvants
      was effective. Protection was not achieved with local cooling, however, topical
      ice did not impair the efficacy of dexrazoxane. CONCLUSIONS: Dexrazoxane is
      extremely effective and apparently quite specific in protecting against lesions
      after s.c. doxorubicin and daunorubicin.

PMID- 11332156
TI  - Metastatic eccrine porocarcinoma: response to docetaxel (Taxotere) chemotherapy.
AB  - BACKGROUND: Eccrine porocarcinoma is an uncommon neoplasm of the intra-epidermal
      sweat gland duct. PATIENTS AND METHODS: A case of eccrine porocarcinoma in a
      female renal transplant patient aged 45 years is described with a review of
      pertinent literature. RESULTS: The primary tumour was highly pleomorphic. In
      places large and small cells merged and focally the former component infiltrated
      the epidermis in a manner akin to Paget's disease of the breast. The majority of
      the tumour was high grade; using the modified Bloom and Richardson grading
      system, usually applied to mammary ductal carcinomas, the tumour graded as 3.
      Metastatic disease developed nine months following primary surgical treatment.
      The metastatic eccrine porocarcinoma was resistant to epirubicin but responded to
      docetaxel chemotherapy. CONCLUSIONS: There are no data to support the use of
      adjuvant therapy in the management of eccrine porocarcinoma. The use of the
      modified Bloom and Richardson grading system may define cases at high risk of
      relapse in which adjuvant therapy might be considered. Metastatic eccrine
      porocarcinoma has proven resistant to many chemotherapeutic agents. We report the
      first use of docetaxel in the management of this disease. The treatment was well
      tolerated and resulted in marked symptomatic and radiological responses.
      Treatment with docetaxel should be considered in future cases of this rare
      tumour.

PMID- 11332157
TI  - Rhinocerebral zygomycosis in a patient with acute lymphoblastic leukemia.
AB  - We report a case of a 28-year-old man with acute lymphoblastic leukemia who
      developed rhinocerebral zygomycosis during induction chemotherapy. This life
      threatening fungal infection is an infrequent cause of neutropenic fever, and is
      occasionally found in patients with leukemia and lymphoma, or patients with
      severely compromised defence mechanisms due to other diseases. It is caused by
      moulds belonging to the Mucoraceae family, and is characterized by local
      destruction of the affected organ. In our patient, the infection spread from the
      paranasal sinuses to the right orbit, destroyed intraorbital structures and
      resulted in blindness within days. Biopsy from the right maxillary sinus was
      performed and mucormycosis was suspected through microscopic examination. Culture
      of the resected specimen identified Rhizopus arrhizus as the causing agent.
      Treatment of zygomycosis should consist of radical surgical debridement of the
      infected tissue, together with intensive broad-spectrum antimycotic therapy with
      amphotericin B. What could be learned from this case is, that aggressive
      approaches to identify the cause of infection is necessary, and that aggressive
      treatment strategies are inevitable to overcome the infection. Furthermore,
      treatment of the underlying disease should be continued as soon as possible.

PMID- 11332158
TI  - Subcutaneous administration of amifostine: a promising therapeutic option in
      patients with oxaliplatin-related peripheral sensitive neuropathy.

PMID- 11332159
TI  - Uneventful administration of cisplatin to a man with X-linked Charcot-Marie-Tooth
      disease (CMT).

PMID- 11332160
TI  - Guidelines for treatment of neonatal jaundice. Is there a place for evidence
      based medicine?
AB  - Treatment of neonatal jaundice continues to be a controversial issue. Arguments
      that traditional practice results in over-treatment have led to the adoption of
      more liberal guidelines in some countries. The importation of liberal guidelines
      from one country to the next, however, is fraught with danger, because
      differences in epidemiology, sociology and healthcare delivery systems between
      countries may not be adequately reflected. The unreflected extension of
      liberalization to non-target groups of patients can expose the latter to
      significant risk. It is not clear that the evidence on which guidelines for
      treatment of neonatal jaundice are based satisfy the requirements for evidence
      based medicine. Evidence of adequate quality may be hard to obtain. CONCLUSIONS:
      Introduction of more liberal guidelines for the treatment of neonatal jaundice,
      if at all contemplated, must be adapted to local circumstances, and any available
      evidence pertaining to local epidemiology, sociology and healthcare organization
      has to be carefully weighed and incorporated. The time is ripe for a joint
      international effort to secure adequate funding for basic and applied research
      within the mechanisms of bilirubin encephalopathy in the newborn.

PMID- 11332161
TI  - Limiting light-induced lipid peroxidation and vitamin loss in infant parenteral
      nutrition by adding multivitamin preparations to Intralipid.
AB  - Parenteral lipids are susceptible to light-induced peroxidation, particularly
      under phototherapy. Ascorbic acid is protective. The aim of this study was to
      investigate whether dark delivery tubing and/or coadministration of multivitamin
      preparations could prevent peroxidation of Intralipid without undue vitamin loss.
      In experiments carried out on the benchtop, lipid peroxidation occurred in
      ambient light and was more extensive under phototherapy. Dark tubing decreased
      peroxide formation, but only by about 65%. In simulated clinical conditions in
      which solutions were pumped through standard clear or dark minibore plastic
      tubing. Intralipid accumulated lipid peroxides as measured by the FOX assay (280
      microM) or as triglyceride hydroperoxides (52 microM). Multivitamin preparations
      (MVIP or Soluvit/Vitlipid) inhibited peroxide formation almost completely, and
      were fully protective when used with dark tubing. There was loss of riboflavin
      (65% from Soluvit and 35% from MVIP) in clear tubing but this was decreased to
      18% and 11%, respectively, in dark tubing. Ascorbate loss was 20% (MVIP) and 50%
      (Soluvit) and only slightly less in dark tubing. Ascorbate loss was also seen in
      the absence of Intralipid and is due to riboflavin-induced photo-oxidation.
      CONCLUSION: Multivitamin preparations protect Intralipid against light-induced
      formation of lipid hydroperoxides, and administering multivitamins with
      Intralipid via dark delivery tubing provides a practical way of preventing
      peroxidation of the lipid while limiting vitamin loss. This procedure should be
      considered for routine use as well as with phototherapy.

PMID- 11332162
TI  - The balance of the autonomic nervous system is normal in colicky infants.
AB  - Excessively crying, hard-to-soothe infants are described as colicky. The self
      limiting course of infantile colic during early infancy suggests an etiology of
      transient developmental dysmaturation. It has been proposed that emotional
      characteristics such as temperament and self-soothing ability are correlated with
      the balance of the autonomic nervous system. Heart rate variability (HRV)
      analysis was used for evaluating the balance of the autonomic nervous system in
      colicky and control infants during and after the colicky period. HRV analysis was
      carried out on 12 colicky infants and 14 control infants at the age of 2 mo, and
      repeated on 10 colicky and 11 normal infants at the age of 7 mo. Measurements
      were performed during polygraphically confirmed slow-wave sleep (sleep stages 3
      and 4). Three HRV frequency bands were defined, including a high (0.2-1.0 Hz),
      middle (0.12-0.2 Hz) and low (0.025-0.12 Hz) frequency variability. There were no
      differences between the study groups in any of the three HRV frequency bands
      analyzed. The high frequency variability increased significantly with age in both
      study groups (p = 0.009). CONCLUSION: The findings suggest that imbalance between
      the parasympathetic and the sympathetic nervous system is not associated with
      infantile colic and that, in accordance with previous findings, control of HRV
      shifts in a parasympathetic direction with increasing age during the first year
      of life.

PMID- 11332163
TI  - Two different doses of gluten show a dose-dependent response of enteropathy but
      not of serological markers during gluten challenge in children with coeliac
      disease.
AB  - In order to study dose-dependency in histopathological reactions and in changes
      of serological markers of mucosal relapse, gluten challenge was performed with
      two defined amounts of gluten in 54 children with earlier enteropathy. Gluten was
      provided in the form of powder and the patients were randomly allotted to either
      0.2 (group A, n = 27) or 0.5 (group B, n = 27) grams per kg body weight per day.
      At the start and after 4 wk of challenge a small intestinal biopsy was performed.
      Biopsy specimens were evaluated, in accordance with defined criteria, graded and
      summarized in an enteropathy score. Blood was sampled at the start and after 2
      and 4 wk of challenge. Serum levels of anti-gliadin antibodies (AGA) and anti
      endomysium antibodies (EmA) were measured. Within 4 wk of challenge, 24 out of 27
      patients in group A and all patients in group B had relapsed. After increasing
      the gluten dose to 0.5 g/kg/d during the subsequent 4 wk, the three non-relapsing
      patients also relapsed. CONCLUSION: The severity of mucosal inflammation was
      significantly higher for group B (p = 0.04) indicating a dose-related severity of
      the enteropathy. No significant difference was found for maximum AGA level, or in
      the proportion of patients that converted to pathological values for AGA or EmA.

PMID- 11332164
TI  - Inhalation of corticosteroids after hospital care for respiratory syncytial virus
      infection diminishes development of asthma in infants.
AB  - The aim of the study was to assess the effect of inhaled corticosteroids on
      subsequent respiratory symptoms and asthma in infants hospitalized for
      respiratory syncytial virus infection (RSV). The study included 188 children
      below 12 mo of age, hospitalized because of RSV infection. During the winter of
      1994/95 only selected children (13%) were given inhaled corticosteroids following
      discharge from the hospital. The following winter (1995/96), almost all children
      (86%) were given this treatment for 6-8 wk. Outcomes of the two different
      treatment regimens were compared by questionnaire 19-24 mo after discharge.
      Children hospitalized and treated during the winter of 1995/96 developed asthma
      (12% vs. 24%) and other severe symptoms of the respiratory tract less often than
      infants treated the year before. The frequency of children with less severe
      symptoms did not differ between the two treatment periods. CONCLUSION: The
      results indicate that inhalation of corticosteroids for 6-8 wk may reduce
      subsequent asthma and severe respiratory morbidity in infants hospitalized for
      RSV infection.

PMID- 11332165
TI  - Tumor- and treatment-related side effects after multimodal therapy of childhood
      intracranial germ cell tumors.
AB  - Multimodality treatment approaches have dramatically improved the outcome of
      patients with intracranial germ cell tumors and are resulting in an increasing
      number of long-term survivors. The aim of the present study was to evaluate
      prospectively the development of side effects in children, adolescents and young
      adults after treatment for intracranial germ cell tumors. Nine patients with a
      median age of 14 y at diagnosis and a median follow-up of 7.25 y underwent a
      detailed long-term evaluation including physical and neuro-ophthalmologic
      examinations, routine laboratory and endocrine stimulation tests,
      neuropsychometric testing, audiometry and spirometry at repeated intervals.
      Endocrine deficiencies requiring hormone replacement therapy occurred in all
      patients. Neuro-ophthalmologic side effects were observed in 8 of the 9 patients,
      urinary electrolyte wasting in 4 of the 9, alopecia in 3 of the 9 and high
      frequency hearing loss in 2 of the 9. Neuropsychologic examinations revealed
      pathologic results in all five tested patients. CONCLUSION: The present study
      indicates that former intracranial germ cell tumor patients suffer from
      remarkable long-term side effects, and that some of these late effects can
      develop or worsen months or years after cessation of oncologic therapy. Since
      life quality is an important parameter of cancer survival, careful follow-up of
      long-term survivors is mandatory, aimed at counteracting side effects as early as
      possible and therefore at minimizing long-term morbidity, which may considerably
      compromise quality of life.

PMID- 11332166
TI  - Changing panorama of cerebral palsy in Sweden. VIII. Prevalence and origin in the
      birth year period 1991-94.
AB  - This 8th Swedish population-based cerebral palsy (CP) report comprises 241
      children born 1991-94. The live birth prevalence was 2.12 per 1000. Excluding 7
      postnatally-derived cases, the gestational age-specific prevalences were 86 for
      extremely preterm children, 60 for very preterm and 6 for moderately preterm, and
      1.3 for term children per 1000. Spastic hemiplegic, diplegic and tetraplegic
      subtypes accounted for 33%, 44% and 6%, dyskinetic CP for 12% and simple ataxia
      for 4%. Neuroimaging had been performed in 90%. Probable aetiology was identified
      in 73% of preterm and 86% of term children. Among preterm children it was
      considered prenatal in 12%, peri/neonatal in 61% and unclassifiable in 27%, while
      it was 51%, 36% and 14% among term children. CONCLUSION: The live birth
      prevalence for CP in the birth year period 1991-94 continued to decrease
      slightly. Gestational age-specific prevalences increased marginally in extremely
      and very preterm births, continued to decrease in moderately preterm births and
      decreased slightly in term births. Probable aetiology and timing of the brain
      insult could be revealed in 81%, birth asphyxia being the likely cause in 28% of
      term children.

PMID- 11332167
TI  - Antenatal magnesium sulphate exposure is associated with prolonged parathyroid
      hormone suppression in preterm neonates.
AB  - The effects of maternal magnesium sulphate treatment on neonatal mineral status
      and parathyroid hormone secretory response were studied in 8 exposed and 27
      control preterm infants during the first 2 wk of life. Antenatal magnesium
      sulphate resulted in hypermagnesaemia during the first 3-7 d of life without
      affecting other serum mineral concentrations. CONCLUSION: Early hypermagnesaemia
      was associated with hypercalciuria during the first 3 d and parathyroid hormone
      suppression up to the age of 2 wk in the exposed infants.

PMID- 11332168
TI  - Smoking related to plasma leptin concentration in pregnant women and their
      newborn infants.
AB  - Leptin, a hormone produced in adipose tissue and placenta, is potentially
      important in relation to energy metabolism and growth. We investigated the effect
      of cigarette smoking on maternal plasma leptin concentration during pregnancy,
      and on plasma leptin concentration and weight among infants up to 13 wk of age.
      Plasma leptin concentration was measured in women in week 18 (n = 203) and week
      35 (n = 164) of pregnancy, while cotinine (nicotine metabolite) was measured in
      plasma sampled from mothers in week 35 of pregnancy (n = 159). Leptin
      concentration was also measured in plasma from the umbilical cord (n = 133) and
      from 4-wk-old (n = 129) and 13-wk-old (n = 130) infants. There was no difference
      in plasma leptin concentration between smoking and non-smoking mothers at 18 wk
      and at 35 wk of pregnancy. Plasma cotinine concentration was higher in smoking
      than in non-smoking mothers, and a negative correlation between plasma cotinine
      and leptin concentrations was found. The leptin concentrations in umbilical cord
      plasma were similar, although the birthweights of newborns from smoking mothers
      were significantly lower than those from non-smoking mothers. The plasma leptin
      concentrations were similar between the two groups also at 4 wk of age. At 13 wk
      of age, infants of smoking mothers had significantly higher plasma leptin
      concentrations than infants of non-smoking mothers. CONCLUSION: Our results
      indicate that a lower birthweight of neonates among smoking mothers is not due to
      altered plasma leptin concentration.

PMID- 11332169
TI  - Neonatal withdrawal syndrome after in utero exposure to selective serotonin
      reuptake inhibitors.
AB  - Selective serotonin reuptake inhibitors (SSRIs) are a new group of
      antidepressants used in mild to moderate cases of depression. In studies
      evaluating the safety of SSRIs during pregnancy, no increase in major anomalies
      has been reported. This might have led to increasing off-label prescription of
      SSRIs to pregnant women. Neonatal withdrawal syndrome commonly occurs in infants
      exposed during the third trimester to drugs known to cause addiction. We report
      five cases of neonatal withdrawal syndrome after third trimester in utero SSRI
      exposure. In three cases the mother used paroxetine in doses from 10 to 40 mg,
      one mother used citalopram 30 mg, and one mother fluoxetine 20 mg. Withdrawal
      symptoms occurred within few days after birth and lasted up to one month after
      birth. Four of the infants needed treatment with chlorpromazine. Symptoms were
      irritability, constant crying, shivering, increased tonus, eating and sleeping
      difficulties and convulsions. CONCLUSION: Neonatal withdrawal syndrome can occur
      after third trimester in utero SSRI exposure. Further research should focus on
      whether it is safe to use SSRIs during the last trimester. All neonates exposed
      to SSRIs during the last trimester should be followed-up closely for withdrawal
      symptoms after birth.

PMID- 11332171
TI  - Early administration of the second dose of surfactant (beractant) in the
      treatment of severe hyaline membrane disease.
AB  - The aim of this study was to demonstrate that administration of the second dose
      of beractant 2 h after the first one is more effective than 6 h after the initial
      dose. The inclusion criteria for the recruitment of newborn infants were: age <
      or = 8 h, birthweight 600-2000 g, gestational age 23-36 wk, need for mechanical
      ventilation with inspiratory oxygen fraction (FiO2) > or = 0.4 and mean airway
      pressure (MAP) > or = 7 cmH2O to obtain arterial oxygen tension (PaO2) values
      between 70 and 80 mmHg, and thoracic X-ray compatible with hyaline membrane
      disease (HMD). Newborns with major congenital malformations, hydrops fetalis or
      severe pulmonary hypoplasia, or being treated with high-frequency oscillatory
      ventilation were excluded. In total, 57 premature newborns were studied, 20 of
      them below 1000 g, who received 100 mg kg-1 of beractant in 2 aliquots and showed
      an inadequate response, i.e. after 2 h of the first dose the newborn still needed
      a FiO2 > or = 0.4 and a MAP > or = 7 cmH2O to achieve a PaO2 > 70 mmHg. The
      second dose was randomly administered 2 or 6 h from the first one. CONCLUSION:
      The 2 study groups were comparable except for a higher need of dopamine and
      seroalbumin in 2-h group. Evolution and complications were similar. Twelve hours
      after the first dose, the percentage improvement in the arteriolar/alveolar ratio
      (a/ADO2) in the 2-h group was similar to that in the 6-h group. However, in
      newborns below 1000 g, 12 h after the first dose the a/ADO2 percentage
      improvement in the 2-h group was greater than in 6-h group (median of 103.6% vs
      16.3%; p = 0.035). In premature infants below 1000 g, it seems reasonable to
      advance the second dose of beractant if needed.

PMID- 11332170
TI  - Effect of publication of the "Practice Parameter for the management of
      hyperbilirubinemia" on treatment of neonatal jaundice.
AB  - The aim of this study was to evaluate the change in the treatment of neonatal
      jaundice following introduction of the "American Academy of Pediatrics' Practice
      Parameter for the management of hyperbilirubinemia in the healthy term newborn".
      In a historical control observation cohort study, we examined the rate of
      phototherapy and exchange transfusions among full-term (> or = 37 wk gestation)
      and near-term (gestational age between 35 and 37 wk and birthweight > 2000 g)
      infants in two community hospitals. The study included all consecutive infants
      born during two 15-mo study periods immediately before and after the introduction
      of the new guidelines. Data were prospectively recorded in a computerized
      database. The rate of phototherapy significantly decreased in the second study
      period from 7.9% (514/6499) to 2.9% (251/8650) (p < 0.0001) among full-term
      infants, and from 20.9% (102/489) to 9.4% (47/502) (p < 0.0001) in near-term
      infants. The use of exchange transfusion was significantly higher (p < 0.001) in
      the first compared to the second period: 0.2% (15/6499) vs 0.03% (3/8650). A
      significant decrease was found when the data from each hospital were analyzed
      separately. CONCLUSION: A significant decrease in the use of phototherapy and
      exchange transfusion occurred after the publication of the new practice
      parameters. This trend was observed for both term and preterm newborns, although
      the new guidelines were not intended for infants born before term.

PMID- 11332172
TI  - Significance of clinical risk factors of cystic periventricular leukomalacia in
      infants with different birthweights.
AB  - Fifteen appropriate-for-date premature low-birthweight infants with cystic
      periventricular leukomalacia (PVL) were studied. The infants were stratified into
      three birthweight groups: less than 1000 g, 1000 g and greater but less than 1500
      g, and 1500 g or greater. Reported and new risk factors for PVL were compared
      with control patients for all patients and each birthweight group. Hypocarbia was
      significantly related to cystic PVL, especially in infants with birthweight 1000
      g or greater (p < 0.03). Sensitivity to hypocarbia might be decreased in infants
      with birthweight less than 1000 g due to therapy or prematurity. In the group
      with birthweight less than 1000 g, the proportion of cystic PVL infants on
      continuous intra-arterial blood-pressure monitoring tended to be lower than the
      controls, with an almost significant difference (p = 0.05). The duration of
      tocolysis was significantly longer in the cystic PVL infants than in the controls
      when the birthweight was greater than 1500 g (p < 0.04). For some risk factors, a
      significant difference or a tendency of difference was demonstrated only after
      stratifying the birthweight. For others, the difference became insignificant
      after stratification. Assessing risk factors after stratifying by birthweight or
      degree of prematurity is therefore useful. CONCLUSION: The results suggest that
      hypocarbia should be avoided to prevent cystic PVL, especially in infants with
      birthweight of 1000 g or greater, continuous intra-arterial blood-pressure
      monitoring may be important in infants with birthweight less than 1000 g, and
      fetal status should be monitored carefully when the duration of tocolysis is
      prolonged, especially in infants with birthweight of 1500 g or more.

PMID- 11332173
TI  - Patent ductus arteriosus and cystic periventricular leucomalacia in preterm
      infants.
AB  - AIM: To test the association between early disturbances in hemodynamics induced
      by left-to-right shunting through the duct and cystic periventricular
      leucomalacia. PATIENTS: Forty-six preterm infants (27-32 wk) admitted to the
      neonatal intensive care unit with risk criteria. METHODS: Patent ductus
      arteriosus was evaluated on days 1 and 4, and was significant (sPDA) in cases of
      absent or reversed end diastolic flow in the subductal aorta. Resistance index
      was measured in the anterior cerebral artery and in the subductal aorta. MAIN
      OUTCOME: Diagnosis of cystic periventricular leucomalacia between day 10 and day
      50. RESULTS: The 12 infants who developed cystic periventricular leucomalacia
      were compared with those who did not. On day 1, sPDA was more frequent (64% vs
      26%; p = 0.03) in the cystic periventricular leucomalacia group, left ventricular
      output was higher (median = 341 vs 279 ml kg-1.min-1; p = 0.005), and rescue
      surfactant was more frequently used (83% vs 47%; p = 0.03). This latter
      association was confirmed by multivariate analysis. Resistance index in the
      anterior cerebral artery was increased in cases of significant patent ductus
      arteriosus (p < 0.01) and was correlated with resistance index in the subductal
      aorta. CONCLUSION: On day 1 in this selected population, sPDA has an effect on
      blood flow velocity waveform in cerebral arteries and is associated with an
      increase in the emergence of cystic periventricular leucomalacia. This
      association could be casual rather than causal.

PMID- 11332174
TI  - Clinical predictors of outcome following mild and moderate neonatal
      encephalopathy in term newborns in Kathmandu, Nepal.
AB  - We describe a clinical grading system for the assessment of neonatal
      encephalopathy developed for a large prospective study in Kathmandu. Inter
      observer variability  testing of our system on 27 infants showed high agreement
      (kappa value 0.87). Validity for the prediction of major neurodevelopmental
      impairment at 1 y of age was tested using a cohort of 57 survivors of
      encephalopathy, all of whom were assessed using a combination of the Denver
      Developmental Screening Test and Bailey 2 at 1 y. We compared this with a
      modification of a scoring system previously validated in Cape Town. Both schemes
      converted a pretest probability of 31% (the prevalence of major impairment at 1 y
      of age in this cohort) to a post-test probability of 55%. This showed only
      marginal improvement over the traditional risk marker of neurological abnormality
      at discharge (post-test probability 51%). At 6 wk of age acquired microcephaly
      increased the probability of major impairment to 79%. CONCLUSIONS: It seems to
      make little difference both in practical or predictive terms whether one
      describes the neurological condition of the neonate using a descriptive or
      scoring system. The important thing is to perform repeated systematic
      neurological examinations on a daily basis during the neonatal period. Many
      clinicians will justifiably continue to use the discharge examination as the
      deciding factor for the need for continued neurodevelopmental surveillance.

PMID- 11332175
TI  - Malassezia pachydermatis fungaemia in a neonatal intensive care unit.
AB  - Malassezia pachydermatis, a non-obligatory lipophilic yeast, has occasionally
      been implicated in nosocomial fungaemias. This study investigated a cluster of
      eight cases of M. pachydermatis infection and colonization in a neonatal
      intensive care unit over a 6 mo period. All patients were preterm with very low
      birthweight and suffered from various underlying diseases. Prolonged use of
      indwelling catheters and parenteral lipid formulations were important
      predisposing factors for their infection. All M. pachydermatis strains were
      susceptible to amphotericin B, fluconazole and itraconazole but resistant against
      flucytosine. CONCLUSION: Molecular typing by random amplification of polymorphic
      DNA showed distinct banding profiles for each blood isolate. Since no
      epidemiological association among the strains could be shown, the reason for this
      cluster of nosocomial fungaemias remains unclear.

PMID- 11332176
TI  - Breastfeeding and complementary feeding practices in rural Malawi.
AB  - To facilitate optimal growth of newborns, many countries have developed infant
      feeding recommendations, usually suggesting 4-6 mo of exclusive breastfeeding and
      then the gradual introduction of complementary foods. We prospectively studied
      the changes in infant diets and predictors of adherence to national infant
      feeding recommendations in a cohort of 720 newborn babies in rural Malawi, Sub
      Saharan Africa. Monthly interviews of the main guardians indicated that
      breastfeeding was universal for 18 mo. As most babies were given water or other
      supplemental foods soon after birth, the exclusive breastfeeding rates were only
      19%, 8%, 2% and 0% at ages 1, 2, 3 and 4 mo, respectively. Complementary foods
      and family foods were introduced at median ages of 2.5 and 6.3 mo, i.e. much
      earlier than recommended. Better adherence to recommendations was associated with
      smaller number of children in the family, increased maternal education and some
      other socio-economic or environmental variables. CONCLUSION: Exclusive
      breastfeeding is uncommon and complementary foods were introduced early to
      newborns among these rural families. Education and family planning may improve
      adherence to infant feeding recommendations and reduce the incidence of early
      childhood malnutrition in Malawi.

PMID- 11332177
TI  - Connections between parental eating attitudes and children's meagre eating:
      questionnaire findings.
AB  - This study investigated whether young children's problematic, meagre eating is
      associated with the eating habits and attitudes of the parents. The subjects, 397
      children, their mothers (n = 397) and fathers (n = 375) participated in a
      prospective atherosclerosis risk-factor intervention trial. The parents evaluated
      their own eating behaviour in questionnaires when their child was 13 mo old. The
      children's eating problems were recorded by the mothers when the child was 13 mo
      old, and by both parents when the child was 5 y old. At both ages, the weight and
      height of the children were measured. Problematic or maladaptive eating habits of
      the children were found to be connected to those of their parents. The mother's
      poor ability to enjoy eating, high tendency to snack and low tendency to eat only
      when hungry, as well as the father's difficulty in maintaining ideal weight
      significantly predicted persistent problems of meagre eating in their children.
      CONCLUSION: The study suggests that the eating habits and attitudes of parents
      may be reflected in the eating behaviour of young children.

PMID- 11332178
TI  - Evaluation of a language-screening programme for 2.5-year-olds at Child Health
      Centres in Sweden.
AB  - A population-based language-screening programme started in the western part of
      Sweden (South Bohuslan) in 1991, with the aim of identifying developmental
      language disability in 2.5-y-old children. The programme was evaluated during
      1998 in an experimental study. A group of 105 2.5-y-old children was recruited
      from 24 separate Child Health Centres. A sample of 25 children with a positive
      screening result was selected. For each of the 25 children, 1-4 controls, i.e.
      children with a negative screening result, were selected. The results were
      reclassified blindly by three speech and language therapists and used as a gold
      standard. Positive and negative predictive values were estimated to be 0.52 (95%
      confidence interval 0.31-0.72) and 0.96 (95% confidence interval 0.89-0.99),
      respectively. Baye's theorem was used to calculate the sensitivity (0.69) and the
      specificity (0.93) of the screening. A method of calculating the sensitivity and
      specificity of the test method by means of three samples was demonstrated.
      CONCLUSION: The data confirm that it is possible to identify reliably children
      with developmental language disability at 2.5 y of age through the screening
      programme.

PMID- 11332179
TI  - Correlation between level of self-regulation in the newborn infant and
      developmental status at two years of age.
AB  - The purpose of this study was to investigate whether the level of self-regulation
      in the newborn baby (a) predicts later cognitive and social development, (b)
      correlates to duration of breastfeeding and (c) has an impact on sleeping rhythm
      and the infant's autonomic behaviour. The study involved 38 full-term infants of
      optimal health who were assessed at an age of 3 d using a screening instrument
      measuring neonatal self-regulation, low, ordinary and high. The instrument, a
      conditional global scale, developed on the basis of the items in the Neonatal
      Behavioral Assessment Scale, identifies three levels of self-regulation. Thirty
      six of the infants participated in a follow-up study at 2 y of age, when they
      were tested with Griffiths' Mental Developmental Scales and one of the parents
      was interviewed about length of breastfeeding, sleeping habits and the infant's
      autonomic behaviour. The results showed that the level of self-regulation was
      correlated to 3 out of 5 variables (Personal-Social development, Hearing & Speech
      and Eye & Hand Coordination) in the Griffiths test. The results also indicated
      differences in sleeping rhythm as well as in breastfeeding patterns between the
      three groups. Furthermore, the study indicated gender-based differences in the
      level of neonatal self-regulation and confirmed previous findings of gender-based
      differences in achieved developmental level at 2 y of age assessed with Griffths'
      Mental Developmental Scales. CONCLUSION: The findings in this study indicate that
      infants with a low level of self-regulation are at risk for poorer social and
      cognitive development as well as regulatory disorders.

PMID- 11332180
TI  - Cord blood endothelin-1 and perinatal asphyxia.
AB  - Discordant data have been reported on endothelin-1 (ET-1), a potent endothelium
      derived vasoconstriction peptide, during the neonatal period, and elevated levels
      have been found in various neonatal diseases. This study evaluated ET-1 in the
      cord blood of 74 neonates of different gestational age, birthweight, mode of
      delivery and 5'-Apgar score. CONCLUSION: Higher ET-1 levels were found in
      neonates born by emergency caesarean section, and in newborns with low 5'-Apgar
      score, suggesting that ET-1 could be a marker of perinatal asphyxia.

PMID- 11332181
TI  - Predictors of recurrent abdominal pain among 9 to 15-year-old urban school
      children in Malaysia.
AB  - A cross-sectional survey of school-children aged from 9 to 15 y was performed in
      the city of Petaling Jaya to look for predictors of recurrent abdominal pain. A
      sample of 1488 children was randomly chosen, of whom 143 (9.6%) had recurrent
      abdominal pain according to Apley's criteria. CONCLUSION: The results of the
      study show that recurrent abdominal pain was associated with a number of
      demographic variables, a tendency to have other complaints and a family history
      of chronic abdominal complaints.

PMID- 11332182
TI  - Enterobacter sakazakii infection in the newborn.
AB  - Enterobacter sakazakii, a Gram-negative bacillus, previously known as "yellow
      pigmented Enterobacter cloacae", is a rare cause of neonatal infection. We
      describe the detailed clinical presentation of two cases in whom E. sakazakii was
      isolated in our neonatal service during the course of 1 mo. These include one
      case of sepsis and meningitis complicated by cerebral infarction, and one case of
      sepsis. In addition, three cases of intestinal colonization were identified. The
      source of the organism was thoroughly sought and was found to be a blender in the
      milk kitchen that was used for preparation of the reconstituted powdered milk
      formula. CONCLUSION: Our paper adds clinical and laboratory information about the
      disease spectrum caused by this relatively rare organism and emphasizes the
      importance of a thorough search for the source of the infection.

PMID- 11332183
TI  - Use of an amino-acid formula in the treatment of colicky breastfed infants.

PMID- 11332184
TI  - [Chlamydia pneumoniae antibody titers in patients with acute ischemic stroke].
AB  - To evaluate an association of ischemic stroke and Chlamydia pneumoniae (C.
      pneumoniae) infection, we investigated specific antibodies to C. pneumoniae by
      ELISA in sera of 91 patients (male 53, female 38, mean age 73 years) with acute
      ischemic stroke. We divided the patients under clinical diagnosis into three
      groups, those with cardiac embolism (E group, n = 35), atherothrombotic
      infarction (A group, n = 29) and lacunar infarction (L group, n = 27). Carotid
      ultrasound examination was performed in 79 patients. The active infection,
      including acute primary infection, reinfection and chronic active infection, was
      defined by IgG or IgA index being > or = 3.00, while inactive infection,
      including previous and chronic inactive infection, was defined by IgG index being
      > or = 1.10 and < 3.00, and IgA index being < 3.00. We found that 20.7% of A
      group, 2.9% of E group, and 7.4% of L group had indexes suggesting an active
      infection (A vs. E. p = 0.040, A vs. L, p = 0.254, L vs. E, p = 0.575: Fisher's
      exact test). The IgG indexes of A group (mean, 1.50) were higher than those of E
      group (mean, 1.35) and those of L group (mean, 0.93, A vs. L, p = 0.049: unpaired
      t-test). The patients with carotid plaque (n = 7) had higher IgG indexes (mean,
      2.28) than those without carotid plaque (n = 72, mean, 1.11, p = 0.002: unpaired
      t-test). These data support the association of acute atherothrombotic infarction
      with chronic active C. pneumoniae infection.

PMID- 11332185
TI  - [Changes of autonomic functions by endoscopic upper thoracic sympathectomy on
      idiopathic hyperhidrosis].
AB  - Changes of autonomic functions before and after bilateral endoscopic upper
      thoracic sympathectomy (EUTS) were evaluated in 13 patients with idiopathic
      hyperhidrosis, with the sympathetic skin response, coefficient of variation of R
      R intervals, mean heart rate, thermography, and non-invasive Valsalva test of the
      tonometry method. EUTS electronically destructs the upper thoracic sympathetic
      ganglions which innervate the upper extremities, and partially the heart. The
      decrement of mean heart rate, and persistent inhibition of the vascular
      contraction and hidrosis of the hands appeared after EUTS. These manifestations
      were effect produced by the abortion of sympathetic activity by EUTS. In 10 of
      the 12 cases, the baroreceptor sensitivity index II of Valsalva test which
      reflects the sympathetic autonomic nervous function of the heart showed normal
      pattern after EUTS. Four cases revealed reincrement of both the blood pressure
      and heart rate at the latter half phase of the second stage of the Valsalva test.
      The sympathetic dysfunction of the heart was limited to the decrement of mean
      heart rate although EUTS partially destroys sympathetic fibers innervating the
      heart. A long-term study is necessary to evaluate the effect of EUTS on the
      cardiac function.

PMID- 11332186
TI  - [An assessment of dysphagia using videofluorography in Parkinson's disease and
      progressive supranuclear palsy].
AB  - We assessed the oropharyngeal swallowing ability in 8 patients with Parkinson's
      disease (PD), 8 patients with progressive supranuclear palsy (PSP), and 10 age
      matched healthy controls (CTL) using videofluorography (VF). In VF studies, PD
      and PSP patients demonstrated food pooling on the tongue, difficulty in bolus
      formation, and bolus falling into pharynx before swallow. PSP patients had a
      significantly longer delay in the pharyngeal phase and showed food falling into
      larynx more often than PD patients (p < 0.05). On measurement of swallowing time
      periods as proposed by Robbins et al., both patient groups showed significantly
      longer periods during many swallowing phases (P < 0.05) compared to those in the
      control group, but there were no significant differences between the PD and PSP
      groups. However, in PSP patients, the time for "transferring the food bolus from
      the oral cavity to pharynx" which we defined as a distinct stage was
      significantly longer (p < 0.05) than that in the PD group. We think that the
      difference in dysphagia characteristics between the two diseases arises from the
      variations in pathological changes in PSP, including those in the cerebral
      cortex, cerebellum, pons and medulla tegmentum in addition to the basal ganglia.
      Dystonia in the neck muscle also plays a role in dysphagia in PSP patients.
      Levodopa medication, changing the form of foods and training in rehabilitation
      techniques such as the chin down posture, supraglottic swallowing and ice-massage
      of the oral region are probably effective for dysphagia in PD patients. In
      patients with PSP, there are few research reports about the treatment of
      dysphagia. However, several dysphagia treatments seem to be useful depending on
      the abnormal patterns in the VF. Further studies are necessary to establish more
      effective treatments for dysphagia in PD and PSP.

PMID- 11332187
TI  - [A survey of current nutrition therapy for the ALS patients in Japanese national
      sanatoriums].
AB  - To evaluate the current nutrition therapy for the patients of amyotrophic lateral
      sclerosis (ALS) in Japan, we sent questionnaires to 53 Japanese national
      sanatoriums (hospitals) and were able to collect replies from 42 institutes. In
      these replies, information on 466 patients (262 inpatients and 204 outpatients)
      was reported, accounting for about 10% of all Japanese ALS patients. Patients who
      ate orally were more frequent (p < 0.001, chi 2 test) in the outpatients (76.0%)
      than in the inpatients (39.7%). When the subjects were limited to non-orally
      nourished cases, gastrostomy was more frequently performed (p < 0.05, chi 2 test)
      in the outpatients (49%) than in the inpatients (29.1%), but no significant
      differences were observed between the above two groups as to the quantity of
      daily caloric intake; the mode was 1000-1200 Cal. About a quarter of non-orally
      nourished patients received supplemental sodium chloride, and fewer were
      supplemented copper and/or zinc. The consent of the patients as well as the
      clinical findings weighed heavily in the determination of the feeding route. Most
      physicians were disinclined to encourage tube feeding in the early stage of
      dysphagia, but were supportive of the operation of percutaneous endoscopic
      gastrostomy when non-oral nutrition therapy became necessary. Although the
      efficacy of vitamins for ALS has not been proved, 45 of 58 physicians agreed to
      subscribe vitamins to their patients, especially vitamin B12, E and C.

PMID- 11332188
TI  - [A patient with motor neuron syndrome clinically similar to amyotrophic lateral
      sclerosis, presenting spontaneous recovery].
AB  - We report a patient with motor neuron syndrome similar to amyotrophic lateral
      sclerosis (ALS) and with spontaneous recovery. At the age 40, the woman developed
      progressive muscular weakness, atrophy and fasciculation in extremities. She also
      noted a dyspnea, tongue atrophy and dysphagia. A neurological examination 6
      months after onset revealed i) a tongue atrophy and fasciculation, ii) diffuse
      muscule weakness and atrophy in face, neck and extremities, and iii) marked
      hyperreflexia in the four limbs and bilateral Babinski reflex, but iv) neither
      sensory disturbance nor ophthalmoplegia. Electromyogram (EMG) detected such
      denervation potentials as fibrillation potentials, fasciculation potentials,
      positive sharp waves and polyphasic or giant MUPs diffusely in the limb muscles.
      Peripheral nerve conduction study detected neither conduction block nor delay.
      Thus, she was diagnosed as suffering from ALS. However, since approximate 1 year
      after onset, her muscle weakness has gradually been getting better.
      Simultaneously, the dyspnea and dysphagia gradually improved. Two years after
      onset, an EMG examination detected chronic denervation potentials in the left
      musculus sternocleidomastoideus and a few on-going denervation potentials in the
      left musculus extensor carpi radialis, but no denervation potentials in other
      limb muscles. Fasciculation potentials were found in tongue muscles. Thus, the
      present case was thought to have a reversible motor neuron syndrome clinically
      quite similar to ALS. A mild increase in IgE (346 U/ml) and a low-titer IgM-class
      anti-GM1 antibody were found in her serum though its pathological significance
      was uncertain. Any immunological aberrance may account for the pathogenesis. It
      should be noted that clinically diagnosed cases of ALS may rarely recover
      spontaneously.

PMID- 11332189
TI  - [Vascular and metabolic reserve in a case of hypoplasia of bilateral internal
      carotid arteries].
AB  - We report a 64-year-old right-handed man who presented with a hypoplasia of
      bilateral internal carotid arteries (ICAs). The patient complained of a vertigo
      and was diagnosed as having a benign paroxysmal positional vertigo. Upon
      neurological examination, he was completely free from neurological deficits. MR
      angiogram revealed an occlusion of both ICAs. On conventional angiogram, the
      right ICA was occluded about 3 cm distal from its origin, and the left ICA was
      occluded at the precavernous portion. There was an abundant collateral blood flow
      to the frontal, temporal and parietal lobes through the posterior communicating
      arteries. Both carotid canals were hypoplastic on 3D-CT. The patient was then
      diagnosed as having a hypoplasia of both ICAs. Using a positron emission
      tomography (PET), cerebral blood flow (CBF), cerebral metabolic rate for oxygen
      (CMRO2), oxygen extraction fraction (OEF), and vascular transit time (VTT) were
      measured during resting state, and the vascular reactivities to carbon dioxide
      inhalation (VRCO2), and to the intravenous administration of Acetazolamide
      (VRACZ) were also evaluated. There was no global or focal reduction in CBF and
      VTT was within normal limit, whereas a global reduction of CMRO2 caused mild
      decrease in OEF. Moreover, VRACZ was significantly decreased and an intracerebral
      steal phenomenon was observed in the parietal cortical areas, whereas VRCO2 was
      preserved. The discrepancy between VRACZ and VRCO2 observed could be related to
      the differences in the mechanisms underlying the vasodilating effects of carbon
      dioxide and ACZ.

PMID- 11332190
TI  - [Familial pure akinesia].
AB  - We report a 67-year-old man and his family presenting pure akinesia (PA). He
      developed bradykinesia. A neurological examination showed a lack of facial
      expression but no tremor or rigidity. His eye movement was full, and he had
      frozen gait and pulsion symptoms. There was no evidence of dementia. Levodopa
      therapy was not effective. Magnetic resonance imaging revealed no brainstem and
      cerebellar atrophy. 99mTc-ECD-SPECT had no further abnormality. His father and
      brother had similar symptoms as him. We conclude that this family is the first
      reported example of pure akinesia with autosomal dominant inheritance.

PMID- 11332191
TI  - [A case of multiple intracranial cavernous angiomas presented with dementia and
      parkinsonism--clinical and MRI study for 10 years].
AB  - We report a case of multiple intracranial cavernous angiomas with serial clinical
      examination and with MRI imaging for 10 years. The patient, 72 years old woman,
      had slowly progressive postural tremor and Parkinsonism followed by dementia.
      Pathological confirmation of cavernous angioma was obtained. At the age of 62,
      brain MRI study demonstrated hydrocephalus, multiple small hypointensity dots in
      cerebellum and cerebral white matter, and reticulated cores predominantly
      adjacent to the ventricles on T2-weighted images. Serial MRI imaging shows that
      the number of small dots has markedly increased and that hypointense lesions
      surrounding reticulated core, corresponding to hemosidern deposit, have extended.
      This case indicates that probably due to chronic compression and continuous
      hemorrhage' multiple and long-standing intracranial lesions could cause dementia
      and Parkinsonism, which are uncommon symptoms of cavernous angioma.

PMID- 11332192
TI  - [A case of welder presenting with parkinsonism after chronic manganese exposure].
AB  - A 56-year-old welder working for 30 years developed postural instability and
      writing clumsiness since October, 1998. Neurologic findings revealed dystonia of
      the bilateral shoulders and distal four limbs as well as parkinsonism such as
      masked face, bradykinesia, rigidity, and retropulsion. Brain MRI showed
      hyperintensity lesions on T1-weighted images in the bilateral globus pallidus,
      midbrain, pontine tegmentum, dentate nucleus and cerebral white matter, which
      reduced in size and density after ten months. The diagnosis of manganese
      poisoning was made by the high manganese levels of both serum and urine, and by
      the marked elevated urinary manganese level after administration of the cheleting
      agent. We pointed out the diagnostic significance of brain MRI in patients with
      chronic manganese exposure.

PMID- 11332193
TI  - [A familial case of spinocerebellar ataxia type 8 (SCA 8)--its clinical findings
      and an issue about the genetic basis].
AB  - We report a 28-year-old woman with spinocerebellar ataxia type 8 (SCA 8). This
      patient began to exhibit dysarthria at the age of 19. At the age of 25, she fell
      and hit her head while drunk and then a neurosurgeon found that her cerebellum
      was atrophic on cranial CT and MRI. Neurological examination on admission to our
      hospital revealed ataxic speech, limb ataxia and mild hyperreflexia without
      Babinski's sign. Cranial MRI showed only mild atrophy of the cerebellar
      hemispheres and vermis. Based on the results of genetic analysis, which showed
      expanded CTG repeats[(CTA) 13 (CTG) 5 (CCG) 4 (CTG) 124] on the SCA 8 locus at
      13q21, she was diagnosed as having SCA 8. As clinical signs of SCA 8, Koob et al.
      reported limb spasticity and diminished vibration perception including cerebellar
      ataxia. Furthermore, Hirose et al. and Satoh et al. reported cases showing
      involuntary movements such as myoclonus or chorea including cerebellar ataxia.
      Our case and Ikeda's cases presented a pure cerebellar phenotype. We think that
      SCA 8 exhibits clinical heterogeneity. On the other hand, Stevanin et al. and
      Worth et al. expressed doubt as to whether the SCA 8 locus at 13q21 is the gene
      actually responsible for autosomal dominant cerebellar ataxia (ADCA). We conclude
      that it is necessary to accumulate additional case reports, and to further
      investigate the relationship between the clinical findings and the results of
      genetic analysis in order to determine whether or not the SCA 8 locus at 13q21 is
      the genetic basis for ADCA.

PMID- 11332194
TI  - [A case of Marchiafava-Bignami disease that responded to high-dose intravenous
      corticosteroid administration].
AB  - We report a 63-year-old male who presented acute confusional state with prominent
      rigidity of all extremities. The patient had a long history of alcoholism and was
      in poor physical condition and malnourished. The diagnosis of Marchiafava-Bignami
      disease was indicated by T2-weighted MRI demonstrating high signal intensity in
      the corpus callosum. Because Wernicke's encephalopathy was suspected as a
      complication, thiamine therapy was applied, but there was no clinical
      improvement. Immediately after high-dose intravenous corticosteroid
      administration was started, his symptoms rapidly resolved except for mild
      cognitive impairment. It is supposed that edematous change in the early stages of
      Marchiafava-Bignami disease causes impairment of the blood-brain barrier. Steroid
      therapy may prevent such a process by means of its the anti-edema effect and by
      normalizing blood-brain barrier. The present case suggests that corticosteroid
      therapy has beneficial effects for Marchiafava-Bignami disease.

PMID- 11332195
TI  - [Lewis-Sumner syndrome presenting unilateral quadriceps amyotrophy as an initial
      symptom].
AB  - We report a 55-year-old man with a chief complaint of wasting and weakness of the
      left quadriceps muscle. At age 54, he noticed difficulty in running and weakness
      in the left thigh, which gradually progressed. On the first admission to our
      hospital, based on the nerve conduction studies (NCS), the muscle biopsy findings
      showing neurologenic changes, and no abnormality of spinal MRI, we diagnosed as
      unilateral quadriceps amyotrophy, which resulted from an atypical form of spinal
      progressive muscular atrophy. One year later, he showed the bilateral hand
      weakness, conduction blocks on the right median and ulnar nerves by NCS, and the
      presence of serum anti-GM 1 antibody. From these findings, Lewis-Sumner syndrome
      was diagnosed. The therapy of high-dose intravenous immunoglobulin moderately
      improved his symptoms. The clinical symptoms of quadriceps amyotrophy is produced
      by various disorders including spinal progressive muscular atrophy, spinal
      extradural arachnoid cyst, rimmed vacuole myopathy, Becker dystrophy, limb-girdle
      dystrophy, and focal myositis. However, there have been no reports of a case of
      Lewis-Sumner syndrome. It is important to consider Lewis-Sumner syndrome in the
      differential diagnosis of quadriceps amyotrophy.

PMID- 11332196
TI  - [Effects of tandospirone citrate on frozen gait in patients with early stage of
      progressive supranuclear palsy, investigated by walk-induced activation single
      photon emission computed tomography method].
AB  - We reported a 64-year-old woman in the early stage of progressive supranuclear
      palsy presenting as pure akinesia syndrome who showed marked improvement with
      tandospirone citrate. She revealed bradykinesia, severe frozen gait and
      disturbance of postural reflex without rigidity or tremor. Treatment with L-dopa
      and L-threo DOPS was not effective, but tandospirone citrate at a daily dosage of
      30 mg significantly lessened the severity of frozen gait. Activation single
      photon emission computed tomography study with 99mTc-ethyl cysteinate dimer
      during gait revealed a significant increase in brain activity in the right
      cingulate cortex after tandospirone citrate treatment. The effect lasted ten
      months until neck rigidity and ventricular supranuclear palsy were evident.

PMID- 11332197
TI  - Protection of mice from LPS-induced shock by CD14 antisense oligonucleotide.
AB  - CD14 is a pattern recognition receptor on myeloid cells and plays a pivotal role
      in an innate immune system that is responsible for Gram-negative and Gram
      positive bacteria infection. Lipopolysaccharide (LPS), a cell wall component of
      Gram-negative bacteria, can induce production of a large quantity of
      proinflammatory cytokines into the circulation mediated by CD14-mediated
      macrophages and monocytes. These cytokines eventually cause septic shock. Several
      in vitro and in vivo studies have shown that suppression of a CD14 function by a
      CD14 antibody led to an inhibition of the production of proinflammatory cytokines
      such as TNF-alpha, IL-1 beta, and IL-8. In the present study, we found that CD14
      antisense oligonucleotide (ODN) can prevent lethal LPS shock in D-galactosamine
      sensitized mice. This ODN inhibited CD14 expression in a mouse macrophage cell
      line, RAW264.7, and suppressed production of TNF-alpha in LPS-stimulated RAW264.7
      cells. Furthermore, we designed a consensus antisense ODN that could hybridize
      human and mouse CD14 RNA, and we evaluated its efficacy. The consensus antisense
      ODN rescued mice primed with Mycobacterium bovis bacillus Calmette-Guerin (BCG)
      from the LPS-induced lethal shock. In this model, the CD14 antisense ODN down
      regulated LPS-elicited CD14 expression in the liver, resulting in a decrease in
      LPS-induced TNF-alpha production. These findings suggest that the CD14 antisense
      ODN is distributed in the liver and efficiently suppresses LPS-induced TNF-alpha
      production by reducing CD14 expression on Kupffer cells. This CD14 antisense ODN
      may be useful for the development of a therapeutic agent against sepsis and
      septic shock.

PMID- 11332198
TI  - Comparison of chromosome aberrations in peripheral blood lymphocytes from people
      occupationally exposed to ionizing and radiofrequency radiation.
AB  - The genotoxic effects of occupational exposure to ionizing and non-ionizing
      radiation were investigated in 25 physicians and nurses working in hospitals and
      in 20 individuals working at radio-relay stations. Examination was conducted by
      chromosome aberration analysis of peripheral blood lymphocytes. The data showed
      that total number of chromosome aberrations in people exposed to ionizing and
      radio-frequency radiation (4.08 +/- 0.37 and 4.35 +/- 0.5 on 200 scored
      metaphases, respectively) were almost equally higher than those of non-irradiated
      subjects. The increase was in proportion to the number of individuals having more
      that 5-aberration/200 metaphases. Acentric fragments comprised the most
      frequently seen type of aberration. The average numbers in examined groups (11.8
      x 10(-3) and 14.8 x 10(-3) per cell, respectively), were significantly higher
      than 4.2 x 10(-3), which was observed in controls, unexposed individuals.
      Dicentric fragments were also frequent (4.8 x 10(-3) and 6.25 x 10(-3),
      respectively, vs. 0.52 x 10(-3) in control). In contrast, the frequency of
      chromatid breaks increased only after ionizing radiation (3.8 x 10(-3) vs. 0.26 x
      10(-3) in control). A positive correlation between the total number of chromosome
      aberrations and cumulative 6-years dosage was also found. The data emphasized the
      dangerous effects of prolonged exposure to both types of radiation and indicated
      that chromosomal aberration analysis should be obligatory for individuals working
      at radio-relay stations.

PMID- 11332199
TI  - Severe fenitrothion poisoning complicated by rhabdomyolysis in psychiatric
      patient.
AB  - Non-traumatic rhabdomyolysis associated with organophosphate intoxication has not
      been generally reported. We report here in a severe case of fenitrothion
      poisoning complicated by rhabdomyolysis. A 43-year-old woman ingested
      approximately 100 ml of fenitrothion emulsion (50%) in an attempt to commit
      suicide. On day 3 after admission, her creatine phosphokinase (CPK) peaked at
      47,762 IU/L. She received supportive treatment included sodium bicarbonate and
      fluid resuscitation. However, muscarinic symptoms including excessive miosis and
      salivation developed on day 5 when her CPK levels decreased. The delay in
      cholinergic symptoms might have been due to the trihexyphenidyl she took with the
      antipsychotic drugs. Fortunately, the present patient recovered from the acute
      cholinergic crisis, and acute renal failure was prevented by early diagnosis.
      This is a case of organophosphate poisoning complicated by rhabdomyolysis in a
      psychiatric patient. The masking of acute cholinergic symptoms should be taken
      into consideration in such patients.

PMID- 11332200
TI  - Biological and genetic markers of sporadic Alzheimer's disease.
AB  - With the development of new treatments, there is an increasing need for early
      diagnosis of sporadic Alzheimer's disease. Therefore, biological markers allowing
      positive diagnosis early in the course of the disease are highly desirable.
      Cerebrospinal fluid levels of protein tau were shown to be significantly
      increased in patients with Alzheimer's disease. Although sensitivity is high,
      poor specificity limits the diagnostic value of this marker. The same is true for
      the 42 amino acid isoform of beta-amyloid protein that is significantly decreased
      in cerebrospinal fluid of Alzheimer's disease patients. However, combining both
      markers could improve specificity at least allowing differentiation between
      Alzheimer's disease, normal ageing and depressive pseudodementia. Other
      biological markers such as cerebrospinal fluid levels of neurotransmitters,
      cytokines or superoxide dismutase were shown to have even less diagnostic value.
      The apolipoprotein epsilon 4 allele is a risk factor for Alzheimer's disease but
      not a diagnostic marker as many individuals who inherit epsilon 4 do not develop
      the disease. Till now, a single diagnostic marker allowing discrimination between
      Alzheimer's disease and other dementias does not exist. Combined cerebrospinal
      fluid levels of beta-amyloid protein and tau protein might be used as a marker
      that helps discriminating Alzheimer's disease from normal ageing and depression.

PMID- 11332201
TI  - Reduced expression of hMLH1 and hMSH2 gene products in high-grade hepatocellular
      carcinoma.
AB  - We performed an immunohistochemical analysis of 2 major DNA mismatch repair
      proteins, human Mut L homologue-1 (hMLH1) and human Mut S homologue-2 (hMSH2), in
      hepatocellular carcinoma (HCC) using 33 biopsied and 58 surgically resected
      specimens, as well as 30 samples from non-cancerous livers. In well
      differentiated HCCs, the immunoreactivity for these antigens was well preserved,
      and the staining intensity was stronger compared to the surrounding liver
      tissues. However, among 41 moderately-differentiated and 9 poorly-differentiated
      HCCs of the resected cases, hMLH1- and hMSH2-positive cells were significantly
      reduced in 19 (38%) and 9 (18%) cases, respectively. In 9 resected tumors, the
      expression of both of these antigens was reduced. Moreover, in 41 tumors of
      differing histological grades, 10 and 5 tumors for hMLH1 and hMSH2, respectively,
      contained a less-differentiated area with a reduced number of immunoreactive
      cells. The samples from non-cancerous biopsied liver and fetal autopsy tissue
      were well immunostained for both hMLH1 and hMSH2. We confirmed in this series
      that the hMLH1 and hMSH2 defect did commonly occur in high-grade HCCs, and that
      it might play a role in tumor progression.

PMID- 11332202
TI  - Biomechanical analysis of weight bearing force and muscle activation levels in
      the lower extremities during gait with a walker.
AB  - The biomechanics of using a walker for the partial weight bearing gait and as a
      method for gradually increasing the muscle activation level were examined with a
      force plate and surface electromyography. The results showed that the weight
      bearing force during gait with a walker is determined by the flexion angle of the
      hip joint. The value remains constant for each stride, indicating that a walker
      can be used for the partial weight bearing gait. Moreover, the muscle activation
      levels in the rectus femoris muscle and biceps femoris muscle per unit time
      during normal gait and gait with a walker with varying hip joint flexion angles
      were found to be correlated with the weight bearing force and to be constant for
      each stride. In addition, the muscle activation level was consistent with the
      level observed during the open kinetic chain resistance exercise with a specific
      loading level. These findings suggest that normal gait and gait with a walker may
      be applicable as a method for gradually increasing the muscle activation level.

PMID- 11332203
TI  - The role of fibronectin in bronchoalveolar lavage fluid of asthmatic patients.
AB  - Allergic and chronic inflammation of the airway is regarded as the main
      pathogenesis of bronchial asthma, in which adhesion of inflammatory cells
      requires the expression of adhesion molecules. Thus, to clarify the role of
      fibronectin (FN) in the airway inflammation of bronchial asthma, FN levels in
      plasma and bronchoalveolar lavage fluid (BALF) from bronchial asthmatics were
      determined. FN concentrations in plasma and BALF were measured by enzyme-linked
      immunosorvent assay (ELISA) in 17 asthmatic patients and 10 healthy controls to
      elucidate the role of FN in allergic inflammation. The mean FN/albumin (Alb)
      level in the BALF of asthmatic patients was 2.973 micrograms/mg, which was
      significantly higher than that of healthy controls (0.727 microgram/mg). Non
      atopic asthmatics showed a significantly higher level of FN in their BALF in
      comparison with atopic asthmatics, although the ratio of FN to albumin showed no
      significant difference. FN levels in BALF correlated significantly with total
      cell density (r = 0.71, P < 0.05) and alveolar macrophage density (r = 0.64, P <
      0.05). FN levels in plasma did not correlate with those in BALF. In conclusion,
      increased FN in BALF, which was produced locally in the airways of asthmatic
      patients, is actively involved in the regulation of allergic inflammation.

PMID- 11332204
TI  - Plasma fibronectin in asthmatic patients and its relation to asthma attack.
AB  - This study investigated the relation between asthma attacks and levels of plasma
      fibronectin (FN) and serum eosinophilic cationic protein (ECP) in patients with
      bronchial asthma in order to clarify the role of FN in the airway inflammation of
      bronchial asthma. Plasma levels of FN were significantly higher (P < 0.025) in
      patients with bronchial asthma than in healthy controls. They were also
      significantly higher (P < 0.05) in non-atopic asthmatics than in atopic
      asthmatics. Furthermore, plasma FN was lower during the attack than the non
      attack stage (P < 0.025), and a significant increase of plasma FN was noted (P <
      0.05) in asthmatics who had more severe and more frequent attacks. Serum levels
      of ECP were significantly higher during the attack than the non-attack stage (P <
      0.005). An increase of plasma FN in the non-attack stage after attacks showed a
      significant correlation (P < 0.05) with a decrease of serum ECP. These
      observations clearly indicate that the decrease in plasma FN associated with
      attacks is closely related to aggravation of airway inflammation, and that the
      increase in plasma FN in the non-attack stage reflects chronic airway
      inflammation. These results suggest that the fluctuation in plasma levels of FN
      may be one of the factors affecting allergic inflammation and attacks in
      bronchial asthma.

PMID- 11332205
TI  - In vitro transformation of rat renal cells by treatment with ferric
      nitrilotriacetate.
AB  - Administration of ferric nitrilotriacetate (Fe-NTA) in vivo causes acute renal
      tubular injury and finally induces renal cell carcinoma. There is accumulating
      evidence that these processes involve free radicals generated by Fe-NTA. To study
      the mechanism of renal carcinogenesis by Fe-NTA, we attempted to induce malignant
      transformation of primary cultured renal cells by treatment with Fe-NTA. When
      primary cultured renal cells (PRC) were treated continuously with Fe-NTA, all of
      the PRC died without transformation. On the other hand, when PRC were treated
      intermittently with Fe-NTA, transformed epithelial colonies were observed at 3
      weeks after the first treatment. The established transformed cell line (RK523)
      showed drastic morphological transformation, grew in soft agar, and formed tumors
      when transplanted into athymic nude mice. These results indicate that the balance
      between cytotoxicity and mutagenecity is important for Fe-NTA induced
      transformation. The RK523 cell line may be a useful model for studying renal
      carcinogenesis in vitro.

PMID- 11332207
TI  - [Spontaneous abortion].

PMID- 11332206
TI  - [Hysterectomy].

PMID- 11332208
TI  - [Ophthalmoscopy].

PMID- 11332209
TI  - [Is there an indication for compression bandages or stockings in the treatment of
      venous leg ulcers? Result of a Cochrane review].

PMID- 11332210
TI  - [SERM--selective estrogen receptor modulators].
AB  - SERM describes a category of drugs that exert their influence on estrogen
      sensitive tissue and are known especially in the treatment of estrogen receptor
      positive breast cancer. The development and clinical trials of new SERM in recent
      years seem to establish more fields of diseases, where treatment with SERM may be
      indicated.

PMID- 11332211
TI  - [Vaginal hysterectomy in non-prolapsed uterus].
AB  - AIM OF STUDY: To describe the results of vaginal removal of the non-prolapsed
      uterus in women conventionally operated on abdominally or with the assistance of
      laparoscopy. MATERIAL AND METHODS: At the departments of gynaecology, Herning
      Central Hospital and Holstebro Central Hospital, approximately one third of all
      hysterectomies are performed vaginally. All records of women, who had had a
      vaginal hysterectomy on a non-prolapsed uterus over a nineteen-month period, were
      reviewed retrospectively. Women, who had additional surgery, were excluded.
      RESULTS: One-hundred and thirteen patients entered. In one patient (1%) the
      vaginal hysterectomy was converted to an abdominal one. One fourth of the women
      had a uterus weighing more than 200 grams. The median operation time was 58
      minutes; 73% bled less than 200 ml. Half of the women were discharged from
      hospital on the third postoperative day or earlier; 90% on the fifth
      postoperative day or earlier. During operation three accidental bladder lesions
      occurred, and four women needed an additional haemostatic operation.
      Postoperatively, 10 women (9%) suffered from a haematoma or an abscess in the
      vaginal vault. CONCLUSIONS: Vaginal hysterectomy on the non-prolapsed uterus is
      an operation that should be offered to a large group of women, who today are
      operated on abdominally or with laparoscopic assistance. The operation is quick
      and the patients are discharged after a few days. No advanced equipment is
      needed. Some women will, however, suffer from a haematoma in the vaginal vault.

PMID- 11332212
TI  - [Spontaneous abortion. Drug treatment versus surgery].
AB  - INTRODUCTION: Studies of conservative management of early miscarriage have
      questioned the need for post abortem curettage. METHODS: A prospective,
      randomised study was carried out to clarify the effect of vaginal administration
      of a prostaglandin E1 analogue (gemeprost) versus surgical management (curettage)
      of miscarriages at up to twelve weeks of gestation. A questionnaire revealed
      discomfort as bleeding and pain. RESULTS: The study comprised 61 patients: group
      1 (n: 27) with an endometrial thickness less than 10 mm managed by expectancy,
      and group 2 with an endometrial thickness greater than 10 mm; group 2 was
      randomised to group 2A (n: 17), given gemeprost, and group 2B (n: 17), underwent
      curettage. On entry the mean gestational ages were 51 and 67.5 days for groups 1
      and 2, respectively; transvaginal ultrasonography revealed a mean endometrial
      thickness of 8 mm in group 1 and 19 mm in group 2. One week later this was
      reduced to 4 mm in group 1 and 5.7 mm in group 2. The duration of vaginal
      bleeding was similar in all groups, with a mean of 1 week (2-3 days of
      moderate/heavy bleeding and 6-10 of no bleeding or spotting). The discomfort
      experienced was similar in all groups (a mean of 36-48 hours of moderate/strong
      pain and 7-10 days of no or insignificant pain). DISCUSSIONS: Conservative
      treatment can substitute general anesthesia and curettage in the management of
      complete spontaneous abortions with fresh vaginal bleeding and an endometrial
      thickness of up to 10 mm. Vaginal administration of 1 mg gemeprost can substitute
      general anesthesia and curettage in the management of incomplete spontaneous
      abortions of up to 12 weeks of gestation and absence of a gestation sac.

PMID- 11332213
TI  - [Anterior screw fixation of fractures of the dens axis].
AB  - INTRODUCTION: The aim of the present study was to evaluate the results of
      anterior screw fixation in the treatment of odontoid fracture. MATERIALS AND
      METHODS: The clinical and radiographic records of the first 14 patients treated
      with anterior screw fixation for odontoid fracture were reviewed retrospectively.
      RESULTS: Satisfying stabilisation of the fracture was achieved in 10 patients
      (71%). In four patients, two of whom had severe osteoporosis, additional
      posterior C1/C2 fusion, owing to failure of screw treatment was needed. Two
      patients developed small occipital bedsores caused by preoperative treatment, but
      no further complications were observed. CONCLUSION: Although only a few patients
      were entered in the study, the results justify the use of anterior screw fixation
      as the treatment of odontoid fracture in selected patients.

PMID- 11332214
TI  - [Aneurysm of the thoracic aorta--a rare cause of fatal obstruction of the central
      bronchial system].
AB  - Two patients presented with severe obstruction of the distal trachea and the main
      bronchi, owing to compression by an aneurysm of the descending thoracic aorta
      (patient 1) and the ascending and descending aorta (patient 2). Both patients
      died from combined respiratory and cardiac failure. Thoracic aortic aneurysm
      should be included in the differential diagnosis of subacute tracheobronchial
      obstruction.

PMID- 11332215
TI  - [Gene therapy of glioblastoma].

PMID- 11332216
TI  - [A comment to a comment. Depleted uranium].

PMID- 11332217
TI  - [Treatment of cancer in Skane and in Sjaelland].

PMID- 11332218
TI  - [Reform of the borderline concept].

PMID- 11332219
TI  - [Guidelines on antibiotics in the Laegeforeningens Medicinfortegnelse 2000].

PMID- 11332220
TI  - [Meningitis].

PMID- 11332221
TI  - [Vegetables and fruit, cultivated in contaminated soil].

PMID- 11332222
TI  - Discharge planning quality from the carer perspective.
AB  - Discharge planning endeavours to assist the transition of patients from the acute
      hospital setting into the community. We examined the quality of discharge
      planning from the perspective of the carer. Spouses were the most common carers
      for the elderly patients in our study. Many carers were also elderly, with their
      own health problems. Using a new instrument (entitled PREPARED) (K. Grimmer and
      J. Moss, Int J Qual Health Care (in press)), carers rated the quality of planning
      for discharge much lower than did the patient, indicating that their needs were
      often not met when discharge was being planned. In free text responses, carers
      expressed their dissatisfaction over communication about how the family would
      cope once the patient went home. Carers generally had lower summary mental
      quality of life scores than the Australian norms (as measured by the SF-36 health
      survey (J. Ware and R. Sherbourne, Med Care 1992; 30: 473-483)), suggesting that
      the caring role may have impacted upon their emotional wellbeing. The rate of use
      of community services in the first week post-discharge was low, suggesting that
      carers and patients carried the majority of the burden immediately after
      discharge. We suggest that planning for hospital discharge requires more
      consideration of the carer.

PMID- 11332223
TI  - The evaluation of the Center for Epidemiologic Studies Depression (CES-D) scale:
      Depressed and Positive Affect in cancer patients and healthy reference subjects.
AB  - This study examined the reliability and validity of a two-factor structure of the
      Center for Epidemiologic Studies Depression (CES-D) scale. The study was
      conducted in a large group of cancer patients (n = 475) and a matched reference
      group (n = 255). Both groups filled in a questionnaire at two points in time;
      patients 3 and 15 months after diagnosis. Factor analysis confirmed our
      hypothesis that the 16 negatively and four positively formulated items measure
      two relatively independent factors, i.e. Depressed Affect and Positive Affect.
      Therefore, these items should not be combined into an overall sumscore. In both
      groups, Depressed Affect proved to be a reliable and valid measure of depressive
      symptomatology, as indicated by its good internal consistency, its strong
      correlations with other measures of psychological distress and neuroticism, and
      its effectiveness in discriminating patients from the reference group on
      depressive symptomatology. In contrast, the validity of the Positive Affect
      factor could not be confirmed, since it was only weakly related to other measures
      of psychological distress and extraversion. Depressed and Positive Affect were
      about equally related to self-esteem, life satisfaction, and quality of life.
      These findings support the use of a sumscore based on the 16 negatively
      formulated CES-D items as a more valid measure of depressive symptomatology, in
      cancer patients and in healthy individuals from the general population.

PMID- 11332224
TI  - Multiple respiratory symptoms predict quality of life in chronic lung disease: a
      population-based study of Australian adults.
AB  - STUDY OBJECTIVES: Previous studies have shown that it is possible to improve the
      health-related quality of life (HRQoL) of chronic lung disease (CLD) patients
      without a concurrent change in morbidity. A valid CLD index that discriminates
      between different levels of CLD severity and is associated with HRQoL status is
      an important tool for primary care settings. In this study a symptom-based CLD
      index was assessed for its validity and relationship with HRQoL in a
      representative Australian population sample. The study also measured the
      prevalence of self-reported CLD. DESIGN: Representative population survey of
      adults aged 18 years and over using a multistage, systematic, clustered area
      sample. SETTING: Metropolitan Adelaide and country centres in South Australia
      with a population of over 1000 persons. PARTICIPANTS: Three hundred twenty-nine
      adults with CLD identified through a representative population survey of 3010
      South Australians. MEASUREMENTS AND RESULTS: The CLD index and the SF-36 were
      administered to participants to assess the association between each subscale of
      the CLD index with each HRQoL scale. The CLD index was also used to assess the
      prevalence of CLD and the distribution of severity in self-reported CLD in the
      South Australian population. Each symptom sub-scale of the CLD index was
      significantly correlated with all scales of the SF-36. The prevalence of CLD as
      measured by the CLD index was 7.7% (mild), 2.2% (moderate) and 1.0% (severe).
      CONCLUSIONS: In the Australian context the CLD index is a reliable patient
      interview instrument that can be used to assess the effects of CLD on general
      HRQoL, improve assessment, and lead to interventions for physicians and their
      patients.

PMID- 11332225
TI  - Perception of quality of life by patients, partners and treating physicians.
AB  - The objective of the study was to determine possible differences in perception of
      quality of life (QoL) between patients with metastatic breast or prostate cancer,
      their partners, and the treating physician. Patients with metastatic breast
      cancer (n = 71), and metastatic prostate cancer (n = 29), a partner, and the
      physician each completed the same QoL questionnaire indicating how they perceived
      the patient's QoL. The European organization for research and treatment of cancer
      (EORTC) QLQ-C30 questionnaire was used to assess patients with breast cancer and
      the modified prostate cancer specific quality of life instrument (PROSQOLI) for
      patients with prostate cancer. There was reasonable agreement in mean scores
      between patients, and physicians or partners, for many domains of QoL; however,
      there was substantial discordance between scores when considering individual
      patients. For patients with metastatic breast cancer, physicians systematically
      underestimated overall QoL (p = 0.0002), social functioning (p = 0.001), and role
      functioning (p = 0.008), while partners showed better agreement. With prostate
      cancer physicians tended to underestimate pain, while mean scores for spouses
      were more concordant. There is substantial variability between ratings of QoL by
      physicians or partners, as compared to patient ratings. Medical decisions should
      be based on information about QoL provided by patients using validated methods.

PMID- 11332226
TI  - Health-related quality of life and virologic outcomes in an HIV clinic.
AB  - OBJECTIVE: The purpose of this study was to describe the relationship between
      viral load and health-related quality of life (HRQOL) in a cohort of persons with
      human immunodeficiency virus (HIV) infection. DESIGN: We evaluated HRQOL
      measurements in a clinical cohort of HIV-positive patients recruited from a
      university-associated HIV primary care clinic. HRQOL instruments included the
      medical outcomes survey-short form-36(MOS-SF-36) from which mental and physical
      component summary scores (MCS and PCS) and subscale scores were calculated.
      RESULTS: Significant negative associations were found between viral load and SF
      36 PCS, physical functioning (PF), role-physical (RP), bodily pain (BP), general
      health (GH), role-emotional (RE), and vitality (VT). Similar negative
      associations were found between CD4 cell count and SF-36 summary and subscale
      scores, with the notable exception of bodily pain. Multivariate analyses
      controlling for the effects of CD4 cell count and other clinical variables
      indicated viral load as an independent predictor of SF-36 PCS, RP, BP and VT
      scores. CONCLUSIONS: The relationship between viral load, a measure of HIV
      disease activity, and several dimensions of the SF-36, a patient-focused measure
      of HRQOL, appears to be strong and independent of CD4 cell count. These findings
      suggest that having a lower viral load positively impacts the quality of life of
      HIV-positive patients.

PMID- 11332227
TI  - Comparison of the psychometric properties of the Asthma Quality of life
      Questionnaire (AQLQ) among 115 asthmatic adults assessed during acute
      hospitalization and as outpatients.
AB  - Health status instruments designed for outpatient settings may not perform as
      intended when applied to hospitalized patients. In this study, we assessed
      similarities and differences between the psychometric properties of the Asthma
      Quality of Life Questionnaire (AQLQ) in-hospital and during an outpatient visit 6
      months later, in a cohort of 115 patients. No ceiling or floor effects were
      present at either visit. At both visits, all scales except for 'environment' had
      internal consistency coefficients > 0.7 (ENVIRONMENT: 0.69--hospitalization; 0.68
      -outpatient). On both occasions, over 75% of item-scale correlation scores were >
      0.4 and over 80% correlated to a greater degree with their own scale total than
      with the other three scales. However, at both visits, the AQLQ standard activity
      items had a higher correlation with the environment scale than with respondent
      defined activity items; this finding re-occurred during exploratory factor
      analysis. Finally, the AQLQ performed similarly in construct validity tests in
      the two settings. In conclusion, this study provides evidence that the AQLQ has
      similar psychometric properties during an acute hospitalization and subsequently
      in an outpatient setting.

PMID- 11332228
TI  - Agreement between a generic and disease-specific quality-of-life instrument: the
      15D and the SGRQ in asthmatic patients.
AB  - The generic health-related quality of life (HRQOL) instrument 15D, and the
      disease-specific St. George's Respiratory Questionnaire (SGRQ) were highly
      correlated in cross-sectional and in follow-up data among asthmatic patients.
      However, a high correlation does not mean that these instruments yield similar
      results about outcome. We measured among 134 asthmatic patients the mathematical
      relationship between the changes in the scores of these instruments by regression
      techniques and agreement by cross-tabulation. The prospective data included
      measurements at baseline and at one, three and five years. The three measurements
      of change in HRQOL were compared with the baseline. There was a close
      mathematical relationship between the scores, but it was affected significantly
      by confounding factors such as patient's age, gender and smoking habits. The
      instruments agreed on the direction of change in HRQOL (positive or negative) in
      64.8% of patients, while in 15.8% the changes were in opposite direction. There
      was a statistically significant difference in indicating the direction of changes
      (improvement or decline) of these instruments. The changes in the SGRQ scores
      agreed slightly better than those in the 15D with the changes in clinical
      parameters. The conclusion was that these instruments do not necessarily yield
      similar results of effectiveness. Therefore, the choice of HRQOL instrument may
      influence the economic attractiveness of different asthma interventions. The
      disease-specific SGRQ agreed slightly better than the generic 15D with the
      changes in clinical parameters.

PMID- 11332229
TI  - [Socioeconomic relevance of acute exacerbations of chronic bronchitis in the
      Federal Republic of Germany. A prospective cost of illness study].
AB  - BACKGROUND AND OBJECTIVE: Prospectively determined data on costs of chronic
      bronchitis were not yet available for the Federal Republic of Germany. The
      purpose of the burden-of-illness-study conducted in the Federal Republic of
      Germany from October 1996 to March 1998 was to calculate direct and indirect
      costs of chronic bronchitis as well as its acute exacerbations per patient and
      year. Furthermore, the health-related quality of life of the patients was
      determined. PATIENTS AND METHODS: The burden-of-illness-study was conducted as an
      open, not randomised surveillance study. The evaluation based on 785 patients
      (55.4% male, 44.2% female, 0.4% unknown; mean age 60 years) who were treated by
      147 general practitioners. 755 patients could be included into the cost analysis.
      RESULTS: Per patient and year direct costs of chronic bronchitis amounted to DM
      1112.27, the calculation of indirect costs resulted in DM 959.09. 41.4% of direct
      costs were due to drug acquisition, hospitalisation costs shared 31.6% and costs
      for physicians' fee amounted to 20.6%. The severity of chronic bronchitis
      revealed significantly different results in cost analysis: per patient, mild
      disease lead to direct costs of DM 387.86, moderate disease to DM 802.62 and
      severe disease to DM 2224.40. This result was caused by higher costs for drug
      acquisition and hospitalisation costs due to chronic bronchitis in higher stages
      of severity. Indirect costs were calculated by applying the human-capital
      approach: 45.8% of indirect costs were due to time-off-work, nursing costs
      amounted to 23.7%. CONCLUSION: The costs of chronic bronchitis have a
      considerable impact on the total costs of the health care system of Germany.

PMID- 11332230
TI  - [Abdominal tuberculosis: a rare differential diagnosis of pancreatic carcinoma].
AB  - HISTORY AND ADMISSION FINDINGS: A 79-year-old local resident, presenting with
      abdominal pain, sweating and weight loss and suspected of having cancer of the
      pancreas was referred for diagnosis and treatment. Physical examination was
      negative except for pain on pressure over the right upper abdomen and the
      epigastrium. INVESTIGATIONS: Erythrocyte sedimentation rate was increased; as
      were the transaminases and cholestasis parameters. Ultrasonography and computed
      tomography of the abdomen revealed an echo-poor mass with cystic areas in the
      region of the head of the pancreas, as well as extra- and intrahepatic dilatation
      of the biliary tract. Endoscopic retrograde cholangiopancreatography failed to
      demonstrate a ductal pancreatic carcinoma. Biopsies of a macroscopically peculiar
      looking duodenal ulcer demonstrated a noncaseous epithelioid granuloma. A fine
      needle biopsy was performed for further diagnosis. DIAGNOSIS, TREATMENT AND
      COURSE: Histological examination of the needle biopsy revealed a caseous
      granuloma and acid-fast bacteria. The tuberculin test (GTI) was strongly positive
      (14-15 mm), indicating tuberculosis of the pancreas and duodenum. Multiple
      tuberculostatics rapidly improved the patient's symptoms, and the further course
      was without complications. CONCLUSION: Tuberculosis should be included in the
      differential diagnosis of consumptive disease with an atypical presentation,
      especially because treatment could well be curative.

PMID- 11332231
TI  - [AIDS and non-Hodgkin's lymphoma: initial cardiac manifestations of highly
      malignant B-cell lymphoma 18 years after HIV infection].
AB  - HISTORY AND FINDINGS: A 35-year-old man who, as a result of intravenous drug
      abuse, had become infected with HIV 18 years previously, was admitted with signs
      of right-heart failure. Three months earlier a systolic murmur had first been
      heard in the 5th intercostal space parasternally. INVESTIGATIONS: Transesophageal
      echocardiography (TEE) demonstrated a 3 x 2 cm right atrial tumour, moderate to
      severe tricuspid regurgitation and pulmonary hypertension. Blood cultures grew
      Streptococcus. DIAGNOSIS, TREATMENT AND COURSE: Endocarditis with atrial thrombi
      and recurrent pulmonary emboli was diagnosed and treated with antibiotics and
      anticoagulants. Three weeks later the TEE showed an increase in the atrial
      tumour. Computed tomography of skull, thorax and abdomen did not demonstrate any
      significantly enlarged lymph nodes. Exploratory thoracotomy revealed an
      infiltrating highly malignant centroblastic non-Hodgkin's lymphoma (NHL) of
      almost the entire free wall of the right atrium. After two courses of
      chemotherapy (CHOP protocol) the size of the tumour had significantly decreased.
      CONCLUSION: The differential diagnosis of a right atrial tumour can be difficult
      in patients with HIV or AIDS. Even if the site is atypical and there is no
      lymphadenopathy, a lymphoma should be considered. In case of doubt a histological
      diagnosis via an exploratory thoracotomy should be performed.

PMID- 11332232
TI  - [Deep venous thrombosis].

PMID- 11332233
TI  - [Intracoronary pressure measurement: importance in the functional assessment of
      coronary stenosis].

PMID- 11332234
TI  - [Oral and inhaled insulin: is it a breakthrough and what does it amount to?].

PMID- 11332235
TI  - [Mental disorders and criminal violence: myths and facts].

PMID- 11332236
TI  - [Treatment of diarrhea in children].

PMID- 11332237
TI  - [Hypertension 2000].

PMID- 11332238
TI  - [Good continuing medical education: too rare in Germany!].

PMID- 11332239
TI  - [Tolerability of a selective cyclooxygenase-2-inhibitor (rofecoxib) in patients
      with intolerance reactions to nonsteroidal anti-inflammatory agents].
AB  - BACKGROUND AND OBJECTIVE: Pseudoallergic reactions triggered by nonsteroidal anti
      inflammatory drugs (NSAIDs) are common and caused by inhibition of the enzyme
      cyclooxygenase-1, whereas their therapeutic effects are mediated by inhibition of
      cyclooxygenase-2. This study analyzed the tolerability of the selective
      cyclooxygenase-2-inhibitor rofecoxib in patients who encountered pseudoallergic
      reactions to NSAIDs. PATIENTS AND METHODS: 37 patients (12 males, 25 females,
      mean age 35 years [15-75 years]) with a history of pseudoallergic reactions to
      NSAIDs underwent standardized skin prick, scratch and patch tests along with oral
      placebo-controlled blinded exposure to rofecoxib (maximum single dose 12.5 mg,
      cumulative dose 25 mg). RESULTS: 23 patients had skin reactions, 4 times
      respiratory symptoms were documented, and in 10 cases cutaneous as well as
      respiratory symptoms were reported. Salicylic acid was identified as the most
      common trigger for a pseudoallergic reaction (n = 28). In 9 cases several non
      steroidal antiphlogistics of different chemical groups caused symptoms. All skin
      tests showed negative results. Oral challenge with rofecoxib was tolerated by all
      37 patients without adverse effects. CONCLUSION: Given the high incidence of
      pseudoallergic reactions to NSAIDs the use of selective cyclooxygenase-2
      inhibitors represents a therapeutic alternative as well as a means of prevention
      of the described reactions.

PMID- 11332240
TI  - [Adult T-cell lymphoma/leukemia: a very rare disease in Europe].
AB  - HISTORY AND CLINICAL FINDINGS: A 45-year-old man was admitted with generalized
      itchy papules. He was originally from the Carribean island of Grenada. The
      disease had started two years before and was diagnosed as lupus erythematosus,
      polymorphic light eruption and atopic eczema. Physical examination showed skin
      colored papules all over the integument, sebostasis and enlarged supraclavicular
      and inguinal lymph nodes. INVESTIGATIONS: Lymphocyte count was elevated with 58%
      as well as LDH (322 U/l) and gamma GT (133 U/l). In a blood smear characteristic
      pleomorphic lymphoid cells (flower cells) could be obtained. Histopathologic
      evaluation demonstrated a subepidermally located infiltrate of pleomorphic
      lymphocytes with epidermal involvement. HTLV-I/II serology (ELISA-screening test)
      was positive. Polymerase chain reaction analysis revealed HTLV-specific
      sequences. DIAGNOSIS, TREATMENT AND COURSE: Diagnosis of adult T-cell
      lymphoma/leukemia was obtained. Treatment consisted of interferon alpha 2b and
      zidovudine which resulted in a rapid response. However, as a result of an
      increased loss of weight (12 kg) this therapy was stopped. Two weeks later
      generalized lymphadenopathy and disseminated skin lesions were observed.
      Chemotherapy (CHOP-scheme) was initiated. The patient deceased with signs of an
      acute leukemia after a short period. CONCLUSIONS: Adult T-cell lymphoma/leukemia
      is a rare disease in Europe. However, in patients with skin rashes, and
      lymphadenopathy, which are originally from HTLV-I endemic areas, adult T-cell
      lymphoma/leukemia should be considered.

PMID- 11332241
TI  - [Case reports of tularemia].

PMID- 11332242
TI  - [Idiopathic pulmonary fibrosis. I. Diagnosis].

PMID- 11332243
TI  - [Idiopathic pulmonary fibrosis. II. Treatment].

PMID- 11332244
TI  - [Calcific aortic valve stenosis: degeneration or atherosclerosis?].

PMID- 11332245
TI  - [Differential diagnosis of tularemia].

PMID- 11332246
TI  - [Compensation for diagnostic errors].

PMID- 11332247
TI  - [Treatment of polycythemia vera].

PMID- 11332248
TI  - [The future internist according to the U.S. model].

PMID- 11332249
TI  - Pancoast tumors.

PMID- 11332250
TI  - [Timely recognition and treatment of hypothyroidism in pregnant women: benefit
      for the child].
AB  - Three women aged 36, 34 and 33 years, with primary hypothyroidism were euthyroid
      whilst on levothyroxine treatment. Two women had previously received 131iodine
      therapy due to Graves' disease. During pregnancy the levothyroxine dose required
      to maintain a normal TSH level increased. The serum TSH-binding inhibiting
      immunoglobulins (TBII) activity was still very high (188 U/l) in one of the
      women, but decreased to 26 U/l in the last trimester. Foetal or neonatal
      thyrotoxicosis was not observed. The levothyroxine dose was decreased after
      delivery and none of the women experienced any adverse effects as a result of
      this. It is recommended that all women taking levothyroxine should have their
      serum TSH activity measured during the first trimester. The daily dose of
      levothyroxine required will usually increase by 50 micrograms during pregnancy.
      The determination of serum TBII activity is indicated in the case of Graves'
      disease; serum TBII values of > 40 U/l constitute a risk of foetal or neonatal
      thyrotoxicosis.

PMID- 11332251
TI  - [The Dutch College of General Practitioners' guideline on urinary tract
      infections: response from the viewpoint of family practice].
AB  - Asymptomatic bacteriuria in healthy non-pregnant women is common, mostly
      transient and benign, whilst antimicrobial drug treatment is highly successful in
      women with a symptomatic and uncomplicated urinary tract infection. So, from a
      practical point of view the need to treat could be solely based on patients'
      preferences and symptoms. Yet recent Dutch professional guidelines have chosen an
      objective diagnosis based on the examination of a urine sample, although
      consensus is still lacking as to the most effective and efficient diagnostic
      method. In the debate about predictive values and the practical consequences of
      the various methods, the differences in the pathological backgrounds of the tests
      can easily be overlooked. Bacteriuria and inflammatory response have a causal
      connection, but reflect distinct phenomena. Symptoms do not necessarily result
      from the former but may result from the latter. Attention needs to be paid to
      these triangular correlations in future studies.

PMID- 11332252
TI  - [The Dutch College of General Practitioners' guideline on urinary tract
      infections: response from the viewpoint of internal medicine].
AB  - In 1999 the Dutch College of General Practitioners (NHG) and the Dutch Institute
      for Healthcare Improvement (CBO) published revisions of their guidelines on
      urinary tract infections. Contrary to previous editions, the revised guidelines
      agree on most points, but not all. To diagnose a urinary tract infection in non
      pregnant women with dysuria, the NHG guideline advises a nitrite test and a dip
      slide culture if the nitrite test is negative. Although the dip-slide improves
      the diagnostic accuracy, a considerable number of patients have to wait at least
      24 hours before therapy is given. The diagnostic approach of the CBO guideline
      uses only rapidly available test results, with the consequence that some women
      are treated despite not having an infection. The NHG guideline advocates the use
      of amoxicillin or nitrofurantoin for pregnant women. Amoxicillin is a
      questionable choice given that about 30% of isolates are resistant to it.
      Nitrofurantoin is in theory a correct choice. However, it is not registered for
      the treatment of complicated urinary tract infections. In the CBO guideline
      amoxicillin-clavulanic acid is considered to be sufficiently safe for the
      treatment of pregnant women because most urinary tract infections occur after the
      first trimester.

PMID- 11332253
TI  - [Guidelines for diagnosing urinary tract infections: advantages and disadvantages
      of various methods].
AB  - The revised guidelines on urinary tract infections from the Dutch Institute for
      Healthcare Improvement (CBO) and those from the Dutch College of General
      Practitioners (NHG), both published in 1999, differ concerning how these
      infections can best be diagnosed. In the case of a negative nitrite test result,
      the Institute advises to count the number of leucocytes or bacteria using a
      microscope, whilst the College advocates just counting the number of bacteria
      using a microscope or assessing bacterial growth by using a dip-slide. The
      difference may be explained by the diagnostic criterion for the numbers of colony
      forming units per millilitre of cultured urine. Leucocyturia with a typical
      history of acute dysuria and frequent voiding might indeed be sufficient as a
      diagnostic tool. However, it is questionable whether this is true in daily
      practice, where many patients with less typical complaints are encountered.

PMID- 11332254
TI  - [Pregnancy (conception) in hyper- or hypothyroidism].
AB  - Pregnancy is accompanied by changes in thyroid function. Due to the increased
      synthesis of thyroid binding globulin and the thyroid-stimulating effect of human
      chorionic gonadotrophin (hCG), serum concentrations of thyroid hormones will
      increase in the first trimester of pregnancy (total T4, T3). Free T4 levels
      decrease during the latter half of pregnancy. Hyperthyroidism during pregnancy is
      usually due to Graves' disease. Definitive therapy may be considered for cases
      prior to pregnancy, although a medical management as would be given during
      pregnancy is an equally good option. The medical management of hyperthyroidism
      consists of a monotherapy with thyreostatics in which the recommended dose needs
      to be adjusted on the basis of free T4 in the high-normal and thyroid stimulating
      hormone (TSH) in the low-normal area so as to minimise the risk of foetal
      hypothyroidism. The transplacental passage of maternal TSH receptor stimulating
      antibodies may cause foetal hyperthyroidism. Another cause of maternal
      hyperthyroidism during pregnancy is 'gestational transient thyrotoxicosis', which
      is associated with high hCG levels during the first trimester of pregnancy. It is
      nearly always accompanied by hyperemesis gravidarum. Hypothyroidism in pregnancy
      has negative consequences for the foetus. If the hypothyroidism is apparent prior
      to pregnancy, it should be corrected before conception (target TSH value of 1
      mU/l). If discovered during pregnancy, treatment with levothyroxine should be
      started as soon as possible. In the case of a pre-existing hypothyroidism a 25
      50% increase in the levothyroxine dosage is often needed during the first
      trimester of pregnancy. This is possibly due to an increased requirement. An
      adequate serum concentration of T4 is necessary for foetal brain development.

PMID- 11332255
TI  - [Sensory neuropathy in HIV infection: pathogenesis and therapy].
AB  - An axonal sensory neuropathy is a frequent complication in the course of HIV
      infection; more than 30% of all HIV-infected individuals will develop a
      polyneuropathy. Low CD4 cell counts and high HIV RNA loads increase the risk.
      This neuropathy causes pain, paresthesias and burning sensations and/or numbness
      in the feet, which sometimes occurs in the hands as well. Neurological
      examination reveals sensory deficits in a stocking and glove distribution and
      depressed or absent ankle reflexes, without severe paresis. The cause of the
      sensory neuropathy is unknown. Either the HIV infection or certain other
      infections, for example cytomegalovirus, may play a role in the pathogenesis;
      vasculitis may be a process associated with this. Some antiretroviral drugs
      within the nucleoside analogue group cause a neuropathy but the pathogenesis of
      this remains unclear. Amitriptyline, tramadol and carbamazepine can be used for
      symptomatic treatment. The efficacy of lamotrigine and gabapentin has yet to be
      confirmed.

PMID- 11332256
TI  - [Summary of the 'Urinary tract infections' guideline (first revision) of the
      Dutch College of General Practitioners].
AB  - The important changes in the Dutch College of General Practitioners' revised
      guideline on urinary tract infections, with respect to the first edition, are as
      follows: In assessing a urine sediment the leucocyte count has been omitted due
      to its low specificity. In the case of a negative nitrite test, the number of
      bacteria is of diagnostic importance. If a microscopic count is difficult to
      carry out, a semi-quantitative culture with a dip-slide is a good alternative. In
      the case of uncomplicated urinary tract infections, nitrofurantoin or
      trimethoprim are the preferred antibiotics, whereas for pregnant women
      nitrofurantoin and amoxicillin without clavulanic acid should be used. The most
      important pathogen is often resistant to sulphonamides. In the case of
      complicated urinary tract infections, characterised by fever, and a still unknown
      sensitivity of the pathogen, amoxicillin-clavulanic acid is recommended except in
      the case of pregnant women. The usefulness of tracing and treating pregnant women
      with asymptomatic bacteriuria has yet to be demonstrated.

PMID- 11332257
TI  - [Diagnostic image (33). Segond fracture with anterior cruciate ligament rupture].
AB  - A 23-year-old man fell on his bent left knee and developed a Segond fracture with
      a rupture of the anterior cruciate ligament.

PMID- 11332258
TI  - [Fecal incontinence in community-dwelling elderly: findings from a study of
      prevalence, consultation of physicians, psychosocial aspects and treatment].
AB  - OBJECTIVE: To gain insight into the prevalence of faecal incontinence, looking
      for medical attention, treatment and the impact of faecal incontinence on the
      quality of life in community-residing men and women of 60 years and over. DESIGN:
      Enquiry and interview. METHOD: A questionnaire about the incidence of faecal
      incontinence and the request for help from the family doctor was mailed in 2000
      to persons aged 60 and older listed in seven general practices in and round
      Nijmegen. In an interview with persons with faecal incontinence questions were
      asked about the need for assistance and the psychosocial consequences of the
      incontinence. RESULTS: Of the 3887 questionnaires mailed, 3345 were available for
      analysis, from 1536 males and 1809 females. The prevalence of faecal incontinence
      was 6%. The male-female distribution was equal and a rise in prevalence was seen
      with advancing age. One-third of the population discussed the incontinence with
      their physician, more women (58%) than men (42%). The faecal incontinence had
      hardly any impact on daily or social activities but the subjects did feel
      anxiety, shame or frustration. Treatment, if given (14/17), consisted of a
      prescription for diapers (n = 2) or of referral to an internist for examination
      of the intestines (n = 4). CONCLUSION: Faecal incontinence occurred in 6% of
      persons aged 60 or older living independently. Explicit looking for medical
      attention was not common. There were hardly any male-female differences. The most
      impact on the quality of life concerned the emotional wellbeing. Treatment had a
      little effect.

PMID- 11332259
TI  - ['Licorice hypertension' also caused by licorice tea].
AB  - A 41-year-old woman, who presented with (apparent) essential hypertension, was
      treated with atenolol and candesartan. This treatment, however, was unsuccessful.
      After the addition of hydrochlorothiazide (HCT) to the combination, she developed
      hypokalaemia with muscle cramps and weakness. This hypokalaemia persisted for
      more than 4 weeks after discontinuation of HCT and starting potassium suppletion.
      As a result of polyuria (> 4000 ml/day) found in a 24-hour urine collection, it
      was discovered that the patient drank at least 3 litres of liquorice tea a day.
      She had denied eating liquorice sweets, a well-known cause of hypertension in the
      Netherlands, but no one had thought of asking her if she drank liquorice tea.
      Blood pressure and serum potassium normalized about 2 months after she stopped
      drinking liquorice tea, and medication was withdrawn. In a patient presenting
      with hypertension and hypokalaemia, who denies eating liquorice sweets, one
      should consider the consumption of other products containing liquorice such as
      liquorice tea. In the Netherlands liquorice tea is increasingly popular and has
      recently become available on a large scale. Therefore more cases such as the one
      described may be expected in coming years.

PMID- 11332260
TI  - [Complicated but successful resuscitation after amniotic fluid embolism].
AB  - A 33-year-old woman, gravida IV, para III with unexplained polyhydramnios was
      admitted to give birth at 29 weeks of pregnancy. Directly after the spontaneous
      breaking of the membranes, asystolia occurred. Following emergency resuscitation
      the sinus rhythm returned. Upon the relaparotomy due to a large filling
      requirement and increasing abdomen size, 'crush' lesions to the spleen and liver
      were visible; following this a splenectomy was carried out and tampons applied to
      the liver. After seven months the patient had slight residual symptoms; three
      weeks after his birth her son was transferred in good condition to another
      hospital. Amniotic fluid embolism is a rare complication of pregnancy with often
      serious complications for mother and child. The diagnosis is based on the
      clinical symptoms of cardiac arrest or sudden profound shock, acute respiratory
      failure, and/or disseminated intravascular coagulation, occurring in most cases
      during or soon after delivery, in the absence of an alternative cause (in
      particular primary cardiopulmonary causes). If the clinical picture deviates from
      the expected post-resuscitation course alternative diagnoses or resuscitation
      injuries must be considered.

PMID- 11332261
TI  - [Denial of requests for euthanasia or assisted suicide is often based on a lack
      of appreciation of insufferable pain, availability of alternative treatments and
      the presence of depressive symptomatology].

PMID- 11332262
TI  - [Surgery for a recently symptomatic severe carotid stenosis, or not? Clinical
      application of 'evidence-based' medicine].

PMID- 11332263
TI  - [Teaching to inhale: better utilization of powder inhalators after counseling and
      instruction].

PMID- 11332264
TI  - [Postoperative heparin-induced thrombopenia with thromboembolism (HITT)--a rare
      complication of heparin therapy?].
AB  - Many surgical patients receive either unfractionated or low-molecular weight
      heparin in a prophylactic or therapeutic intention. Feared upon the
      administration of heparin is the heparin-induced thrombopenia (HIT). In HIT type
      1, the heparin directly interacts with the platelets. The platelet count rarely
      falls below 100,000/microliter and normalizes again despite continuous
      administration of heparin. In HIT type 2 or HIT with thrombosis (HITT) the
      platelet count usually falls more than 50% and due to an antibody-dependent
      platelet activation, thromboembolic episodes may occur. Compared to non-surgical
      patients, the incidence of HITT in the postoperative phase is markedly increased.
      In suspicion of a HITT, heparins should immediately be stopped and replaced by an
      alternative coagulant because of a high risk of further thromboembolic
      complications. Direct thrombin-inhibitors such as the recombinant hirudins are
      considered to be safe and effective. They have no heparin-like immunological
      properties and therefore, they seem to become the therapeutic and prophylactic
      "gold-standard" in patients with HITT.

PMID- 11332265
TI  - [Stomach surgery--are the requirements for specialist in general surgery still
      realistic?].
AB  - This paper discusses the possibility for a surgical trainee to acquire the
      necessary experience in gastric operations for his fellowship in general surgery.
      All operations of the stomach performed at the surgical unit of Lucerne Hospital
      between January 1994 and September 1997 were analysed retrospectively. Of 184
      operations performed only nine were done by a trainee, four of which were
      gastrostomies and five operations of a perforated ulcer. These results prove the
      difficulties for a trainee to achieve the required number of operations. Possible
      solutions would be the acknowledgement of assisted operations for the fellowship
      in general surgery and/or the limitation of gastric operations performed by the
      trainee himself to the curriculum for the fellowship in visceral surgery.

PMID- 11332266
TI  - [Treatment of diaphyseal pseudarthrosis by circular external fixator].
AB  - The aim of this retrospective study was to evaluate the effectiveness of circular
      external fixator according with Ilisarov technique for the treatment of
      diaphyseal pseudarthrosis. The union rate obtained in our serie was 91%. We
      assessed the complications related to surgery and analysed the reasons for failed
      technique. Between january 1986 and february 1996, 23 patients were included in
      this study with a mean follow-up of 65 months. The period of external fixation
      was 209 days on average. 21 patients had united fractures. The failures were
      attributed to inadequate interfragmentary contact. The main problem during
      treatment was pin tract infection. The late complications included axial
      deformities, re-fractures and joint stiffness. Circular external fixator proved
      to be useful for the treatment of diaphyseal pseudarthrosis, particularly those
      complicated by infection or post-traumatic shortening.

PMID- 11332267
TI  - [Distal radius fractures--retrospective quality control after conservative and
      operative therapy].
AB  - BACKGROUND: The distal radius fracture is the most frequent fracture in the adult
      patient. The wide spectrum of different types of fracture and the coexisting
      factors make the choice for the optimal treatment difficult. As an interne
      quality control we retrospectively evaluated all patients with distal radius
      fractures treated in 1995 at our institution. METHODS: The study included 69
      adult patients with 71 distal radius fractures. After on average 26 months 58
      patients with 59 fractures were clinically and radiologically evaluated. The
      patients were asked to give supplementary information about their follow-up
      treatment as well as any remaining physical difficulties and limitations in the
      daily life. All x-rays of the broken radius were carefully analysed and compared
      with the opposite side. The final results were evaluated according to the
      "Demerit Point System". RESULTS: Patients were treated with five different
      therapeutical methods. 76.3% of the patients showed a very good/good final
      result. In 56.7% of the cases secondary fracture dislocation occurred; the
      dislocation-rate of fractures treated with percutaneous k-wires was 93.3%! A
      clear correlation between secondary displacement and final results was found.
      CONCLUSION: A main factor for an optimal outcome is the anatomic restoration of
      length and axis of the distal radius as well as of joint congruency, also
      moderate angular deformities are well tolerated. Our collective showed an
      unexpected high rate of secondary displacement, especially in the k-wire group.
      The reasons for this unsatisfactory event are manifold: too optimistic
      indication, insufficient follow-up examination in the first four to six weeks,
      inconsequent change to a more stable fixation method in case of a secondary
      dislocation. The results of this retrospective evaluation had a major impact on
      our concept of treatment. The dorso-radial double-plate technique combined with
      bone graft will be more used in the future especially in younger patients. The
      new standardised concept is the base of a present prospective study.

PMID- 11332268
TI  - [Preliminary results of retrograde nailing of the humerus].
AB  - A group of nine patients with a diaphyseal fracture of the humerus and treated
      with retrograde nailing were studied with a mean follow-up of 15.3 months. Six
      patients with a humeral fracture without neurological deficit showed a good
      shoulder and elbow mobility at the last visit. Three patients with neurological
      lesion preoperatively suffer from a diminished range of movement not related to
      the surgical procedure. During the operation and postoperatively we found no
      complication related to the implant and more precisely we could not find a
      iatrogenic fracture or nervous lesion except one intraoperative lesion of the
      radial nerve probably related to an important traction movement during reduction
      with complete remission. Consolidation has been achieved for all fractures but
      one. This patient suffers from a lesion of the brachial plexus with complete
      plegia of the arm and a vascular lesion. This patient had to be reoperated for an
      atrophic non-union by bone grafting and plate fixation. The retrograde nail is a
      good implant and must be considered in our treatment plans as much as
      conservative treatment or surgical treatment with plating, anterograde nailing or
      the use of an external fixator. Only then will we be able to give to the patient
      the most adapted treatment for his fracture.

PMID- 11332269
TI  - [Intercostal nerve syndrome].
AB  - The intercostal nerve syndrome is caused by an impingement of the intercostals
      nerve at the level of the anterior rectus sheath. It may lead to acute or chronic
      abdominal pain, it should therefore be considered in the differential diagnosis
      of the acute or chronic abdomen. A positive Carnett-test and an effective local
      anaesthesia at the point of maximal tenderness allow the correct diagnosis. In
      our retrospective study 14 patients with 15 entrapment syndromes are described.
      If, sometimes after a few diagnostic and therapeutic detours, the diagnosis is
      established, surgical intervention with resection of the altered nerve at it's
      exit of the anterior rectus sheath can usually abolish the pain with little side
      effects.

PMID- 11332270
TI  - Successful endovascular repair of a leaking abdominal aortic aneurysm under local
      anesthesia.
AB  - Local anesthesia is a safe and less invasive anesthetic management for the
      endovascular approach to elective aortic aneurysm. We have successfully extended
      the indication of local anesthesia to a high-risk patient with leaking aneurysm
      and stable hemodynamics. PATIENT AND METHODS: A 86 year old patient with renal
      insufficiency due to longstanding hypertension, coronary artery and chronic
      obstructive lung disease was transferred to our hospital with a leaking abdominal
      aortic aneurysm. Stable hemodynamics allowed to perform a fast CT scan, that
      confirmed the feasibility of endovascular repair. A bifurcated endograft (24 mm x
      12 mm x 153 mm) was implanted under local anesthesia. RESULTS: The procedure was
      completed within 85 minutes without problems. The complete sealing of the
      aneurysm was confirmed by CT scan on the third postoperative day. Twenty months
      later, the patient is doing well and radiological control confirmed complete
      exclusion of the aneurysm. DISCUSSION: The endoluminal treatment is a minimally
      invasive technique. It's feasibility can be rapidly assessed by CT scan. The
      transfemoral implantation can be performed under local anesthesia provided that
      hemodynamics are stable. This anesthetic management seems to be particularly
      advantageous for leaking abdominal aortic aneurysm since it doesn't change the
      hemodynamic situation in contrast to general anesthesia. Hemodynamic instability,
      abdominal distension or tenderness may indicate intraperitoneal rupture and
      conversion to open graft repair should be performed without delay.

PMID- 11332271
TI  - [Cystic adventitial degeneration of the external iliac artery--a case report with
      long-term follow-up].
AB  - The cystic adventitial degeneration of the external iliac artery is an extremely
      rare disorder with only 10 cases described in literature. It should be considered
      as the possible origin of unilateral claudication symptoms with sudden onset in
      relatively young individuals without other vascular disorders. Further
      investigations should be done before admission to surgical therapy. The classic
      surgical procedure consists in arterial excision and interposition grafting with
      saphenous vein. We report one case treated by exarterectomy without recurrence
      after three years.

PMID- 11332273
TI  - Complete sequence and organization of Periplaneta fuliginosa densovirus genome.
AB  - The replicative form (RF) of the Periplaneta fuliginosa densovirus (PfDNV) genome
      was cloned and its complete nucleotide sequence was determined. The PfDNV genome
      is 5454 nucleotides (nt) in length with distal 201-nt long inverted terminal
      repeats (ITRs). The first 122 nt at the 5'-end and the terminal 122 nt at the 3'
      end of both strands are palindromes with identical sequences, of which each can
      fold into a typical U-shaped hairpin structure. The coding regions of PfDNV
      genome are evenly distributed in the 5'-halves of both strands. PfDNV genome
      contains seven major open reading frames (ORFs), four of which on the plus DNA
      strand may encode non-structural (NS) proteins, while the others on the minus DNA
      strand may encode structural proteins. Two potential functional promoters (P3 and
      P97) were found within the ITRs on both strands. The ORF2 polypeptide contains a
      highly conserved NTP-binding domain of NS proteins of parvoviruses. The ORF5
      polypeptide has significant homology to the conserved PGY region of coat proteins
      of parvoviruses. The ORF6 polypeptide has distinct homology to the structural
      polypeptides of insect parvoviruses. The organization of PfDNV genome was
      compared to those of other parvoviruses.

PMID- 11332272
TI  - Comparative study on genomes of two Japanese melon necrotic spot virus isolates.
AB  - Nucleotide sequences of the genomes of two Japanese Melon necrotic spot virus
      (MNSV) isolates, NH and NK were determined. The open reading frames (ORFs) in
      both genomes encode five proteins: p29 (the pre-readthrough domain of p89), p89
      (the readthrough domain of p89 identified as the putative RNA-dependent RNA
      polymerase), p14 (the pre-readthrough domain of p7A), p7A (the putative movement
      protein), and p42 (coat protein, CP). Nucleotide and amino acid sequence
      identities of the five proteins of NH and NK isolates were estimated at 97.4
      99.5% and 97.7-100%, respectively. NK isolate but not NH isolate infected
      systemically leaves of Cucumis melo plants. When deduced amino acid sequences of
      p7A proteins of NH and NK isolates were compared, only one difference at position
      16 (serine in NH isolate and isoleucine in NK isolate) was observed. p7A protein
      is considered the putative movement protein. The serine of p7A protein of NH
      isolates may be involved in systemic infection. In addition, phylogenetic
      relationships of genes based on nucleotide sequences revealed that NH and NK
      isolates might form a group, and S isolate, serologically different from NH and
      NK isolates, might represent a distinct isolate not belonging to this group.

PMID- 11332274
TI  - Localization of Plum pox virus in stem and petiole tissues of apricot cultivars
      by immuno-tissue printing.
AB  - Localization of Plum pox virus (PPV) in stem and petiole tissues of four
      susceptible and four resistant apricot cultivars has been studied. Consecutive 1
      mm spaced transverse sections were taken from the tissues and were printed onto
      nitrocellulose membrane in duplicate. For virus-specific detection, one series of
      prints was probed with an antibody to PPV coat and the density of stains was
      evaluated by light microscopy. Another series of prints was treated with a
      substrate but not with the antibody to reveal non-specific staining due to
      endogenous peroxidases. The virus was currently detected in all inoculated
      susceptible cultivars but only in one inoculated resistant cultivar (Harcot). In
      the stem tissues, the virus was localized in the pith and in the xylem. In the
      petiole tissues, it was localized in the epidermis and in cortical and medullae
      parenchyma. Non-specific staining was observed only in the stem sclerenchyma and
      in the petiole phloem.

PMID- 11332275
TI  - Efficiency of inoculation of peach GF305 seedlings with Plum pox virus by
      different methods.
AB  - Peach GF305 is frequently used as rootstock in experiments to evaluate the
      resistance of different species of Prunus to Plum pox virus (PPV) because of its
      extreme susceptibility. However, transmission of PPV in Prunus species is
      sometimes problematic due to its low concentration or uneven distribution in
      these species. To determine the most effective way of transmitting the virus,
      different infection methods (by aphids, grafting, mechanical infection and
      injection) were tested using Dideron PPV isolates. The most effective method was
      the grafting of herbaceous material with inoculum derived from similar herbaceous
      material. Infection by aphids was more laborious and less effective than
      grafting, showing many disadvantages. Neither mechanical infection nor injection
      transmitted the virus.

PMID- 11332276
TI  - Characterization of RKZ isolate of ovine herpesvirus 1.
AB  - Cytopathic effect (CPE) characterized mainly by foci of rounded cells was
      observed in cultures of primary plexus choroideus cells from healthy lamb
      following cryopreservation. It was possible to transmit the infectious agent to
      other primary cells of ovine origin by co-cultivation with infected cells. By
      indirect immunofluorescence microscopy it was found that high percentage of sheep
      (65-80% in 3 different herds from Slovakia) are infected with this infectious
      agent. Electron microscopy of cells with CPE revealed the presence of herpesvirus
      particles. Viral DNA was isolated from infected cells using pulse-field gel
      electrophoresis and further used as probe in Southern blot analysis. The probe
      reacted specifically only with DNA from cells infected with Ovine herpesvirus 1
      (OvHV-1) but not with DNA of other ruminant herpesviruses. Some of the HindIII
      restriction fragments of DNA of the obtained OvHV-1 isolate denominated RKZ were
      cloned. Part of the H9 clone was sequenced identifying a gene that encoded a
      polypeptide homologous to conserved herpesvirus VP23 structural protein. From
      comparison of the sequence of this clone with VP23 sequences of other
      herpesviruses it was deduced that OvHV-1 might be classified within the
      Rhadinovirus genus of the Gammaherpesvirinae subfamily. The sequencing of the H9
      clone of DNA of RKZ isolate enabled establishment of sensitive and highly
      specific polymerase chain reaction (PCR) assay for detection of OvHV-1.

PMID- 11332277
TI  - Comparison of manganese superoxide dismutase precursor induction ability in human
      hepatoma cells with or without hepatitis B virus DNA insertion.
AB  - In a previous study (Hajnicka et al., Acta virol. 38, 55-57 (1994)), we described
      synthesis of a 23 K protein in high amounts in the PLC/PRF/5 human hepatoma cell
      line after stimulation with sera of patients suffering from liver cirrhosis. In
      this study we identified this protein as manganense superoxide dismutase (Mn
      SOD). When PLC/PRF/5 cells stimulated by various cytokines (interleukin-1 alpha
      (IL-1 alpha), IL-1 beta, tumor necrosis factor-alpha (TNF-alpha), TNF-beta, IL-6,
      tumor growth factor-alpha (TGF-alpha), TGF-beta, and interferon-gamma (IFN-gamma)
      were compared, the most effective was IL-1, followed by TNF-alpha and IL-6. Other
      cytokines had no effect on the stimulation of Mn-SOD. IL-1 alpha was selected for
      stimulation of Mn-SOD production in four human hepatoma cell lines (PLC/PRF/5,
      Hep-3B, Hep-G2 and Sk-Hep 1). Maximum Mn-SOD production occurred in PLC/PRF/5
      cells. In other cell lines, Mn-SOD production was lower, reaching 35.7% and 31.5%
      in Hep-3B and Sk-Hep-1 cells, respectively, while it was only 4.3% in Hep-G2
      cells.

PMID- 11332278
TI  - Characterization of cypovirus isolates from tropical and temperate Indian
      saturniidae silkworms.
AB  - Cytoplasmic polyhedrosis virus (cypovirus, CPV) isolates from larvae of
      saturniidae silkworms Antheraea mylitta, Antheraea proylei, and Antheraea
      assamensis were obtained and characterized. Scanning electron microscopic (SEM)
      studies revealed the presence of hexahedral (rhombic dodecahedron) polyhedral
      bodies of various size (1-4 microns) in individual hosts while transmission
      electron microscopic (TEM) studies of isolated virions showed their uniform
      (icosahedral) shape and size (approximately 55 nm). Genomes of these isolates
      were obtained from purified polyhedral bodies and analyzed by agarose and
      polyacrylamide gel electrophoresis. Eleven bands ranging from about 350 bp to 3.9
      kb (total of 25.35 kb) were detected. These bands were completely degraded after
      treatment of the genome preparations with RNase A at low salt but not at high
      salt concentration. The banding pattern of the genomes remained unaffected by
      treatment of the respective preparations with DNase I, indicating that the
      genomes were composed of 11 double-stranded (ds) RNA segments. The RNA banding
      patterns of the CPV isolates from the saturniidae silkworms were similar to each
      other. These characteristics were similar to that of Antheraea mylitta cypovirus
      4 (AmCPV-4) but different from that of Bombyx mori cypovirus 1 (BmCPV-1). In
      comparison to AmCPV-4 the isolates contained an additional, eleventh RNA segment
      and the size of the RNA segments was also different. Dot blot hybridization
      showed hybridization of the cloned 9th and 10th segment cDNAs from the A. mylitta
      CPV (AmCPV) isolate with RNAs from the A. proylei and A. assamensis CPV (ApCPV,
      AaCPV) isolates but not with RNA from BmCPV-1. Polyacrylamide gel electrophoresis
      in the presence of sodium dodecyl sulfate (SDS-PAGE) of polyhedral proteins from
      the AmCPV isolate showed the presence of 3 major and 5 minor bands of M(r) from
      29.4 K to 163 K, but BmCPV-1 polyhedral bodies showed different protein banding
      pattern. Two heterologous cell lines infected with the AmCPV isolate showed very
      slow virus growth with the accumulation of polyhedral bodies in the cytoplasm of
      infected cells indicating a restricted host range of this CPV isolate.

PMID- 11332279
TI  - Effect of tunicamycin on expression of epitopes on Japanese encephalitis virus
      glycoprotein E in porcine kidney cells.
AB  - The effect of tunicamycin (Tm), a glycosylation inhibitor, on the epitopes
      expressed on Japanese encephalitis virus (JEV) glycoprotein E (gpE) in porcine
      kidney stable (PS) cells was studied. At Tm concentration of 2 micrograms/ml, the
      virus-infected cells showed markedly reduced or no reactivity with any of the
      monoclonal antibodies (MAbs) directed against JEV gpE except NHs-2 and also with
      polyclonal antibodies (PAbs) directed against JEV. With the increase in Tm
      concentration to 3 micrograms/ml, a complete loss of the conventionally detected
      reactivity of the MAbs except NHs-2 was recorded, while the Pabs showed no
      decrease in their reactivity. However, the MAb NHs-2 and PAbs lost their
      reactivity when the cells treated with 3 micrograms/ml Tm were stained for
      epitopes expressed on their surface indicating that glycosylation plays a role in
      this phenomenon. Tissue culture fluid (TCF) displayed a low virus content in the
      presence of 3 micrograms/ml Tm, indicating probably a down-regulation of virus
      maturation inside the cells. Since preM and NS-1 proteins possess besides gpE
      conserved N-glycosylation sites and play a role in the maturation of JEV, their
      expression in nascent, i.e. non-glycosylated form might be responsible for the
      observed low virus content of TCF. Thus, the glycosylation of JEV gpE seems
      essential for the acquisition of native conformation of its epitopes and their
      expression in cells.

PMID- 11332280
TI  - Modest increases in the titers of helper virus-free herpes simplex virus 1 (HSV
      1) vectors by packaging in a cell line with inducible expression of HSV-1 VP16 or
      by treatment with N,N'-hexamethylene-bis-acetamide.
AB  - A recently developed helper virus-free HSV-1 vector system has potential for both
      gene therapy and physiological studies, but relatively low vector titers have
      complicated use of this system. In this report, we explored improving the vector
      titers by isolating a Vero cell line that uses the tetracycline-regulated
      promoter system to induce HSV-1 VP16 at the beginning of the packaging procedure.
      We isolated the required cell line and demonstrated that it supports enhanced
      expression from a HSV-1 immediate early (IE) promoter. However, use of this cell
      line in helper virus-free vector packaging results in only a modest,
      approximately 2-fold increase in the vector titers. Additionally, treating the
      packaging cells with N,N'-hexamethylene-bis-acetamide (HMBA), which is known to
      induce HSV-1 IE promoters, also supports only modest increases in the vector
      titers. These results suggest that the lack of VP16 is not the rate limiting
      factor in the packaging procedure.

PMID- 11332281
TI  - Red swamp crawfish (Procambarus clarkii): an alternative experimental host in the
      study of white spot syndrome virus.
AB  - The pathogenicity of white spot syndrome virus (WSSV) for the red swamp crawfish
      (Procambarus clarkii) was investigated after infection by intramuscular (i.m.)
      injection and oral route. The cumulative mortality of crawfish injected i.m. with
      WSSV reached 100% in 5 days. After oral feeding WSSV-infected kuruma shrimp
      (Penaeus japonicus) muscle tissues to the crawfish the cumulative mortality of
      this host reached 100% in 11 days. On reinfection trials, all the crawfish fed
      WSSV-infected crawfish muscle tissues died in 9 days. All the shrimp injected
      with a filtrate of infected crawfish heart tissues died in 12 days with typical
      signs of white spot syndrome (WSS). Electron microscopy clearly demonstrated that
      WSSV propagated in the cells of the crawfish midgut. This study showed that the
      red swamp crawfish can be used as alternative experimental host in the study of
      WSSV.

PMID- 11332282
TI  - Emergential success: a new concept for a better appraisal of viral emergences and
      reemergences.

PMID- 11332283
TI  - Long-term follow up of multibacillary leprosy patients with high BI treated with
      WHO/MDT regimen for a fixed duration of two years.
AB  - Forty-six, newly detected, previously untreated multibacillary (MB) patients with
      a bacterial index (BI) of > or = 3+ who had received WHO/MDT for 2 years were
      followed up for a total duration of 424 person-years and a mean duration of 9.26
      +/- 2.98 years per patient. The BIs of the patients continued to fall, and all of
      the patients, except one, reached skin-smear negativity. WHO/MDT was well
      accepted and well tolerated. Relapse, which was defined as an increase in the BI
      of 1+ or more with or without clinical evidence of activity, was observed in only
      one patient, giving a relapse rate of 2.2% or 0.23 per 100 person-years in
      patients with a BI of > or = 3+ after long-term follow up. This patient was
      started on a second course of WHO/MDT to which he responded favorably. WHO/MDT
      for a fixed duration of 2 years for MB patients as recommended by the WHO is
      vindicated.

PMID- 11332284
TI  - Frequency and extent of thickening of the nucleated epidermis in leprosy lesions.
AB  - Using 28 specimens of clinically normal skin from lepromatous leprosy subjects as
      a standard for comparison, the mean thickness of the nucleated epidermis was
      found to be significantly increased in untreated lesions from 16 borderline
      tuberculoid, 21 erythema nodosum leprosum (ENL), and 14 reversal reaction
      patients, but was unchanged in borderline lepromatous and lepromatous patients.
      Using specimens from 36 untreated lepromatous and borderline lepromatous lesions
      as the standard for comparison with the lesions of reversal reactions or ENL
      which these patients eventually developed, there was a significant thickening of
      the nucleated epidermis in both reactional states. In both comparison groups,
      there was a greater mean increase and a larger frequency of thickening in the ENL
      lesions than in those with reversal reactions. In the borderline tuberculoid and
      reversal reaction lesions the increase can be understood as secondary to the
      presence of gamma interferon or interleukin-2. The increase in thickness in the
      ENL lesions is more difficult to explain, but it is not inconsistent with a role
      for these same two cytokines.

PMID- 11332285
TI  - Immuno-histopathology in the diagnosis of early leprosy.
AB  - The present study of 45 early leprosy cases in an endemic area in China
      indicates: a) Sensitivity of acid-fast bacilli (AFB) detection can be
      significantly improved by examining approximately 30 serial sections. AFB and/or
      phenolic glycolipid-I (PGL-I) were mostly detected in the infiltrates in the
      subepidermal zone, intraneurium, perineurium and around blood vessels. b) PGL-I
      antigen was positive in 10 clinically suspected, single lesion leprosy cases and
      AFB positive in 7 patients, AFB and/or PGL-I in nerve in 6 patients. c)
      Nonspecific chronic inflammation in indeterminate leprosy presented as selective
      perineural and/or intraneural infiltration with lymphocytes predominating. In the
      infiltrating mass, fragments of neural tissue were demonstrated with anti-S-100
      protein staining. d) Except for 3 cases with unknown numbers of lesions, the
      present positive immunohistopathological findings are in direct correlation with
      the number of lesions at first diagnosis, namely: 41.6% (10/24) for single
      lesion, 66.6% (6/9) for 2 lesions, and 88.8% (8/9) for patients with > or = 3
      lesions. e) Typical epithelioid or macrophage granuloma formations were not seen
      in early leprosy with a single lesion. In testing the immunological inclination
      of these patients with CD68 or tumor necrosis factor-alpha (TNF-alpha) a positive
      test is likely to be of prognostic value since TNF-alpha is involved in granuloma
      formation and nerve damage.

PMID- 11332286
TI  - Antileprosy protective vaccination of sooty mangabey monkeys with BCG or BCG plus
      heat-killed Mycobacterium leprae: immunologic observations.
AB  - Groups of sooty mangabey monkeys (SMM) were vaccinated and boosted with
      Mycobacterium bovis bacillus Calmette-Guerin (BCG), or BCG + low-dose (LD) or
      high-dose (HD) heat-killed M. leprae (HKML), or were unvaccinated. Prior to and
      following vaccination-boosting and subsequent M. leprae (ML) challenge, these and
      unvaccinated, unchallenged control monkeys were immunologically observed
      longitudinally for approximately 3 years. SMM [multibacillary (MB) leprosy-prone
      as a species] were not protected clinically by BCG or BCG + HKML, although the
      disease progress was slowed by vaccination with BCG alone. The longitudinal
      immune response profiles to BCG or BCG + HKML in SMM showed that: 1) vaccination
      with BCG or BCG + HKML initially stimulated significant in vitro blood
      mononuclear cell blastogenic responses to ML antigens, which returned to baseline
      post-boosting and post-live ML challenge; 2) BCG + LD HKML-vaccinated groups gave
      the largest blastongenic response (SI = 23) followed by the BCG + HD HKML group
      (SI = 14.5) and by the BCG-only vaccinated group (SI = 3.6); 3) significantly
      diminished numbers of blood CD4+ (helper) and CD4+CD29+ (helper-inducer) T-cell
      subsets were observed longitudinally in all ML-challenged groups compared to
      controls regardless of whether they had been vaccinated or not; 4) CD8+
      (suppressor) T-cell numbers remained longitudinally constant, on average, in all
      ML-challenged groups (vaccinated or not) compared to controls; 5) there was a
      significant decrease in the CD4+:CD8+ ratio over time in all ML-challenged groups
      (vaccinated or not); 6) vaccination with BCG or BCG + LD or HD HKML resulted in
      significantly increased numbers of CD4+CD45RA+ (suppressor-inducer) T cells
      longitudinally compared to the unvaccinated, ML-challenged control group; and 7)
      over time, vaccination with BCG + HKML followed by live ML-challenge produced
      higher IGM:IgG antiphenolic glycolipid-I (PGL-I) serum antibody response ratios
      than BCG-only vaccinated, ML-challenged monkeys or unvaccinated, ML-challenged
      SMM, consistent with prior observations that IgG anti-PGL-I responses correlate
      with resistance to and protection from clinical leprosy and IgM anti-PGL-I
      responses correlate with increased susceptibility.

PMID- 11332287
TI  - Regulation of nitric oxide induced by mycobacterial lipoarabinomannan in murine
      macrophages: effects of interferon-beta and taurine-chloramine.
AB  - We examined the effects of interferon beta (IFN-beta) on the production of
      liporabinomannan (LAM)-induced nitric oxide (NO) in peritoneal macrophages from
      low-responder and high-responder (C3H/HeJ and C3H/OuJ) mice. NO was produced in a
      dose response when induced by lipo-polysaccharide (LPS) or LAM plus interferon
      gamma (IFN-gamma) or IFN-beta in both high- and low-responder mice. In contrast
      to IFN-gamma, both high- and low-responder mice failed to induce nitrite
      production when IFN-beta was added, except at a high concentration of IFN-beta.
      Tau-Cl (0.5 mM) inhibited NO production about 50% in the high-responder strain
      when cells were activated with LPS or LAM in combination with either IFN-beta or
      IFN-gamma, and almost abolished NO production at 1.0 mM. In the low-responder
      strain, Tau-Cl (0.5 mM) significantly inhibited NO production when cells were
      activated with IFN-gamma or IFN-beta in addition to LPS or LAM, but did not
      completely inhibit NO production at 1.0 mM. Tau-Cl appears to play a potent role
      in regulating inflammatory reaction-induced bacterial or mycobacterial organisms.
      These data indicate a pivotal role for IFN-gamma and IFN-beta for the production
      of LPS and LAM initiated NO in peritoneal macrophages from low-responder
      (C3H/HeJ) mice.

PMID- 11332288
TI  - A Mycobacterium leprae isolate resistant to dapsone, rifampin, ofloxacin and
      sparfloxacin.
AB  - Mycobacterium leprae were isolated from a Japanese patient, and susceptibility to
      antileprosy drugs was examined by the mouse foot pad method. The isolate was
      susceptible to clofazimine and clarithromycin, and resistant to dapsone,
      rifampin, ofloxacin and sparfloxacin. Mutations were identified in the genes
      associated with resistance to these drugs. The risk of the emergence of leprosy
      with multidrug resistance is emphasized.

PMID- 11332289
TI  - Use of ML dipstick as a tool to classify leprosy patients.
AB  - Leprosy control services face the problem of leprosy patients being misclassified
      by the lack of or the poor quality of skinsmear examination services.
      Misclassification increases the risk of relapse due to insufficient treatment if
      a multibacillary (MB) patient is classified as paucibacillary (PB), thereby also
      prolonging the time that the patient is infectious. The World Health Organization
      (WHO) recommends at present an alternative classification based on the number of
      skin lesions. Its reliability, however, has been questioned. Our investigation
      sought to determine the usefulness of the ML Dipstick, a simple field assay to
      detect IgM antibodies to phenolic glycolipid-I of Mycobacterium leprae, for the
      classification of leprosy patients in addition to lesion count. In this study,
      264 leprosy patients were investigated. Of 130 patients with a positive bacterial
      index (BI), 19 (14.6%) had less than 6 lesions and would have been classified as
      PB. Out of 134 patients with a negative BI, 26 (19.4%) had 6 or more lesions and
      would have been classified as MB patients if the lesion counting system would
      apply. Thus, the classification based on the number of lesions only was found to
      be 85% sensitive and 81% specific (using the BI as the gold standard) at
      detecting MB cases among the studied population. Sensitivity would have increased
      if patients would have been classified according to a combination of the number
      of lesions and the dipstick result. In that case patients are classified as MB
      when they are either dipstick positive (N = 16), have more than 6 lesions (N =
      43), or both (N = 94). Patients negative for both dipstick and number of lesions
      would have been classified as PB (N = 111). The classification based on the
      number of lesions alone left 19 BI-positive cases classified as PB, while the
      combination method of the ML Dipstick and number of lesions left only 8 BI
      positive cases classified as PB (5 borderline, 2 borderline lepromatous and 1
      tuberculoid), thus preventing undertreatment. The combination method of the ML
      Dipstick and lesion counting was found to be 94% sensitive and 77% specific,
      which is an improvement of 9% (chi-squared test, p = 0.025) in sensitivity
      compared to lesion counting only. The results of this study indicate that testing
      all patients initially classified by lesion counting as PB (48% in our study
      population) with the dipstick can significantly contribute to improved
      classification of leprosy patients for treatment purposes.

PMID- 11332290
TI  - Estimating hidden prevalence in Hansen's disease through diagnosis delay and
      grade of disability at time of diagnosis.
AB  - The objective of the present study was to propose a new method for the
      calculation of estimated hidden prevalence (EHP) in Hansen's disease (HD). We
      analyzed the records of 4142 HD patients diagnosed in the state of Rio Grande do
      Sul, Brazil, between 1970 and 1991. Out of these 4142 cases, 3291 patients had
      their grade of disability (GD) evaluated at the time of diagnosis and provided
      information about the time elapsed between the appearance of the symptoms and the
      moment when HD was identified by a physician (diagnosis delay, DD). Mean DD for
      the sample (in years) was 1.51 for disability grade 0, 2.14 for grade 1, 4.46 for
      grade 2, and 9.64 for grade 2. EHP was calculated taking into account only two
      strata of GD using the formula HP = [(NC-GD 0/1) x 2.0 + (CN-GD 2/3) x 5.0]/(CGE
      x PCP), where: NC-GD 0/1 = mean annual number of newly detected grades 0 or 1
      cases; CN-GD 2/3 = mean annual number of newly detected grades 2 or 3 cases; CGE
      = proportion of newly detected cases with GD evaluated; PCP = proportion of the
      population covered by the state HD control program; 2.0 and 5.0 correspond to an
      approximation of the mean time in years of DD in each respective stratum of GD.
      Applying this model, we found an EHP of 529 cases which translates to an excess
      of 0.58 cases/10,000 population. We also conducted a multivariate analysis using
      a logistic regression model. This analysis revealed that, in addition to DD,
      other variables such as clinical form, age group, sex and mode of detection were
      independent risk factors for the presence of disabilities. We also found two
      significant effect modification factors: DD versus clinical form and DD versus
      age group. Taking these findings into consideration, a more complex model was
      used to calculate the EHP with 16 strata (defined by clinical form of the
      disease, age group, and GD from 0 to 3). An EHP of 502 cases (excess of
      0.55/10,000) was obtained with this more complex model. This result differs only
      5% from that of the simplified model. Therefore, we conclude that the simplified
      model is indicated to estimate hidden prevalence of HD in the field.

PMID- 11332291
TI  - Asthma among the famous. Augustus Caesar (63 B.C.-A.D. 14) first emperor of Rome.

PMID- 11332292
TI  - Measuring outcomes in pediatric asthma.
AB  - The incidence and severity of pediatric asthma continues to increase in developed
      countries throughout the world. In determining what works best in the management
      of the asthmatic child, outcome measurements specific for this population have
      been developed. There are three major categories of outcomes that should be
      addressed in pediatric asthma. First are the clinical and physiologic
      measurements, which include lung functions, clinical symptoms, and number of
      emergency department and hospital visits. Measurement of both generic and disease
      specific health-related quality of life (HQL) is advocated because each provides
      complementary information about how the condition affects everyday functioning
      and well-being, and whether treatments have their intended effects. Finally,
      economic outcomes should be considered, which include direct costs, such as
      physician and medication costs, and indirect costs, such as missing school or the
      parents missing work due to their child's asthma.

PMID- 11332293
TI  - Behavioral issues in asthma management.
AB  - Despite advances in drug treatment, outcomes in asthma remain unsatisfactory.
      Often overlooked in developing treatment strategies are important factors that
      affect outcomes in asthma: behavioral issues such as the low rate of patient
      adherence to the prescribed treatment regimen, inadequate physician-patient
      communication, and inconsistent implementation of evidence-based treatment
      guidelines. The low adherence rates among asthma patients may be improved by
      education programs that emphasize both the potentially serious risks of this
      disease and a team approach to treatment that includes patients and their
      families in developing a treatment plan. Interactive physician education programs
      have been shown to improve guideline implementation and physician communication
      skills. Indeed, effective physician-patient communication may be the key to
      improving guideline implementation and patient adherence, resulting in meaningful
      decreases in asthma-related morbidity and mortality.

PMID- 11332294
TI  - Management and treatment of pediatric asthma: update.
AB  - Much of what we know about the pathogenesis and treatment of asthma has been
      learned from adult studies. Recently, a dramatic shift toward the pediatric age
      group has occurred in both of these areas. Such studies in children have overall
      supported similarities with the adult population with regard to pathogenesis
      (airway inflammation) and treatment (anti-inflammatory controller medications).
      However, the onset of asthma symptoms in less than 5 years is 80% of the time,
      yet controller medications approved for children under 4 years of age have
      generally not been available. This treatment gap was recently filled by the FDA
      approval of two important asthma controller medications. This review will focus
      on the use of leukotriene receptor antagonists and inhaled corticosteroids, which
      were recently approved for use in asthmatic children under 4 years of age.

PMID- 11332295
TI  - Serum ECP taken in the acute episode of bronchial obstruction can predict the
      development of bronchial asthma in young children.
AB  - For the early institution of anti-asthma treatment, reliable markers
      distinguishing the children with asthma from children with virus-associated
      wheeze are needed. Serum eosinophilic cationic protein (ECP) has been suggested
      as a marker correlating with the intensity of eosinophilic inflammation. We have
      studied 27 children (age 3 to 35 months) admitted with acute bronchial
      obstruction. Each child had been followed for 12 months after the first episode
      and then assigned to one of two groups (asthma or non-asthma) based on the
      clinical course. Serum ECP (s-ECP) was taken at the acute episode and again at
      least 6 months later, when the child was completely symptom-free. Serum ECP was
      analyzed using the Pharmacia CAP ECP FEIA immunofluorescence system. Mean s-ECP
      during the acute episode was 26.5 micrograms/L (5.5-69) in the asthma group (n =
      14) and 9.7 (5.2-17 micrograms/L) in the non-asthmatics (n = 13), p < 0.01. There
      was no difference in the s-ECP analyzed during the symptom-free period. Elevated
      values of serum ECP taken during, but not outside, the acute episodes of
      bronchial obstruction may be helpful in predicting the development of bronchial
      asthma in young children with acute obstructive episodes.

PMID- 11332296
TI  - Immunoglobulins in tears and sera in patients with atopic dermatitis.
AB  - The aim of the study was to investigate the role of circulating (i.e., present in
      the serum) and locally produced (i.e., in the lamina propria of mucous membranes)
      immunoglobulins including IgE. The IgG, IgA, IgM immunoglobulins, and IgE (total
      and specific) were measured in patients' sera with atopic dermatitis (AD) (n =
      93). As control subjects 83 healthy volunteers, matched for sex and age, were
      included. The IgG and IgM levels were within the normal range. Mean value of the
      total IgA (2.55 +/- 0.26 g/L, in controls 1.49 +/- 0.32 g/L) and IgE (609 IU/mL,
      in controls below 40 IU/mL) levels were significantly elevated (p < 0.05) in sera
      of AD patients. Based on the serum total IgE levels (above or below 40 IU/mL) the
      patients were divided into RAST-positive and RAST-negative types of allergy,
      respectively. RAST-positive AD (n = 79) showed hypersensitivity to inhalant and
      food allergens determined by the specific IgE test. The majority of RAST-positive
      AD cases (n = 68) presented only skin manifestations, while the rest of the
      patients (n = 11) had rhinoconjunctivitis as well. RAST-positive AD patients with
      rhinoconjunctivitis showed an increased IgE level in tears (above 10 IU/mL). The
      specific IgE test positivity in tears correlated with elevated serum total IgE
      levels and specific IgE positivity (r = 0.925). Total and allergen-specific IgE
      in the tears can be used to diagnose allergy in vitro. It is believed that the
      mucosal permeability is enhanced in the atopic inflammatory process, and this may
      facilitate the transmission of environmental allergens.

PMID- 11332297
TI  - Atopic status of an adult population with active and inactive tuberculosis.
AB  - The rise in allergic disorders over the past three decades has been suggested to
      be related to the decrease in infectious diseases. Recently, a negative
      association between tuberculin responses and atopic disorders has also been
      reported. We planned to investigate the effect of natural exposure to
      Mycobacterium tuberculosis on atopic status in patients with active tuberculosis
      and to compare the findings with the data of patients with inactive disease. A
      total of 97 subjects were divided into two groups. Group 1, patients with proven
      active pulmonary tuberculosis (n = 66); group 2, subjects who had a history of
      previous tuberculous disease, with negative bacteriologic studies and no clinical
      and/or roentgenographic evidence of current disease (n = 31). Current history of
      allergic diseases was recorded by a physician with the use of a questionnaire
      adapted from the European Community Respiratory Health Survey (ECRHS), and skin
      prick tests (SPTs) were performed using a standardized panel. Total IgE and
      Phadiatop were measured by the Pharmacia uniCAP system. The rate of one or more
      positive SPTs was significantly lower in the patients with active tuberculosis
      than the inactive group (15% versus 48.4%, p < 0.001). The current history of
      atopic diseases was 7.6% and 29% in the active and inactive tuberculosis groups,
      respectively (p = 0.002). The rate of positive skin tests to inhalant allergens
      in patients with inactive disease was higher than the rate of healthy adult
      Turkish people (48.4% versus 25%, p = 0.001). Geometric mean of total IgE levels
      were lower in patients with inactive disease than patients with active pulmonary
      tuberculosis (74.97 kU/L versus 106.3 kU/L, p = 0.05). The ratios of Phadiatop
      positivity were 21% and 38.7% in the active and inactive tuberculosis groups,
      respectively (p = 0.008). We found lower atopy rates in patients with active
      pulmonary tuberculosis than subjects with inactive disease. Although our data
      support the hypothesis that M. tuberculosis may prevent the development of atopic
      disorders by inducing the production of cytokines antagonistic to Th2
      development, we believe prospective and experimental studies are needed before
      attributing a direct cause-effect link to this association.

PMID- 11332298
TI  - Thyroid autoimmunity in chronic urticaria.
AB  - A subset of patients with idiopathic chronic urticaria (CU) has been recently
      classified as autoimmune on the basis of two main findings: association with
      thyroid autoimmunity and with anti-IgE and/or anti-IgE receptor antibodies. The
      association of CU with thyroid autoimmunity has been known since 1983, but its
      frequency varies in different reports. The objective of the present study was to
      verify the prevalence of thyroid antibodies (anti-thyroid peroxidase, TPO;
      thyroglobulin, TG; TSH-receptor, TSH-R) in two distinct series of CU: of known
      cause (70 cases, group A) and idiopathic (52 cases, group B). Twenty-three
      patients (M/F:7/16) of group A (33%) and 12 (M/F:4/8) of group B (23%) tested
      positive for at least one type of thyroid antibody. The difference was not
      statistically significant. Thyroid disease or altered serum TSH levels (requiring
      treatment) were present in 39% of group A and 42% of group B seropositive
      patients. In conclusion, the present study shows that CU, either of known cause
      or idiopathic, is more common in females than in males and is significantly
      associated with thyroid autoimmunity. These results were not expected on the
      assumption that autoimmune phenomena are a specific pattern of idiopathic CU.
      Thus, screening for thyroid autoimmunity and function is advisable in all
      patients with CU for the early identification of patients requiring either
      treatment of underlying thyroid dysfunction or follow-up.

PMID- 11332299
TI  - Chronic urticaria: mechanisms and treatment.
AB  - Chronic urticaria (CU) is a vexing clinical syndrome. The clinician is challenged
      by the patient's symptoms. The experienced physician can evaluate the CU patient
      and prescribe effective treatment. The following review emphasizes the autoimmune
      mechanisms of CU. Despite this new insight into the pathogenesis of CU, many
      cases are still categorized as idiopathic. CU patients are a heterogenous group
      of patients who require an individualized approach to evaluation and management.

PMID- 11332300
TI  - From nannyism to public disclosure: the BSE inquiry report.

PMID- 11332301
TI  - Mandatory testing: not just an academic discussion.

PMID- 11332302
TI  - Harm reduction or reducing harm?

PMID- 11332303
TI  - Management of patients with uninvestigated dyspepsia.

PMID- 11332304
TI  - On the trail of necrotizing fasciitis in children.

PMID- 11332305
TI  - On the trail of necrotizing fasciitis in children.

PMID- 11332306
TI  - First-line drugs for hypertension.

PMID- 11332307
TI  - Change the Canada Health Act? Why?

PMID- 11332308
TI  - Helping physicians with alcohol problems.

PMID- 11332309
TI  - Policies must keep pace with the evolution of vaccines.

PMID- 11332310
TI  - Breast cancer survival by teaching status of the initial treating hospital.
AB  - BACKGROUND: A number of studies have documented variation in treatment patterns
      by treatment setting or by region. In order to better understand how treatment
      setting might affect survival, we compared the survival outcomes of women with
      node-negative breast cancer who were initially treated at teaching hospitals with
      those of women initially treated at community hospitals. METHODS: We constructed
      a retrospective cohort consisting of a random sample of 938 cases, initially
      diagnosed in 1991, drawn from the Ontario Cancer Registry. Exposure was defined
      by the type of hospital in which the initial breast cancer surgery was performed.
      Outcomes were ascertained through follow-up of vital statistics. RESULTS: The
      crude 5-year survival rate was 88.7% for women who had their initial surgery in a
      community hospital and 92.5% for women who had their initial surgery in a
      teaching hospital. Women in higher income neighbourhoods experienced better
      survival at 5 years regardless of which type of hospital they were treated in.
      Multivariate proportional hazards regression modelling demonstrated a 53%
      relative reduction in risk of death among women with tumours less than or equal
      to 20 mm in diameter who were treated at a teaching hospital (relative risk [RR]
      = 0.47, 95% confidence interval [CI] 0.23-0.96), whereas among those with larger
      tumours there was no demonstrated difference in survival (RR = 1.32, 95% CI 0.73
      2.32). Other variables that were significant in the model were age at diagnosis,
      estrogen receptor status and the use of radiation therapy. INTERPRETATION: Women
      with node-negative breast cancer and tumours less than or equal to 20 mm in
      diameter who were initially seen at a teaching hospital had significantly better
      survival than women with similar tumours who were initially seen at a community
      hospital. Survival among women with larger tumours was not statistically
      significantly different for the 2 types of hospital.

PMID- 11332312
TI  - Benztropine for acute muscle spasm in the emergency department.

PMID- 11332311
TI  - Clinical practice guidelines for the care and treatment of breast cancer: 11.
      Lymphedema.
AB  - OBJECTIVE: To provide information and recommendations for women and their
      physicians when making decisions about the management of lymphedema related to
      breast cancer. OPTIONS: Compression garments, pneumatic compression pumps,
      massage and physical therapies, other physical therapy modalities, pharmaceutical
      treatments. OUTCOMES: Symptom control, quality of life, cosmetic results.
      EVIDENCE: Systematic review of English-language literature retrieved primarily
      from MEDLINE (1966 to April 2000) and CANCERLIT (1985 to April 2000).
      Nonsystematic review of breast cancer literature published to October 2000.
      RECOMMENDATIONS: Pre- and postoperative measurements of both arms are useful in
      the assessment and diagnosis of lymphedema. Circumferential measurements should
      be taken at 4 points: the metacarpal-phalangeal joints, the wrists, 10 cm distal
      to the lateral epicondyles and 15 cm proximal to the lateral epicondyles.
      Clinicians should elicit symptoms of heaviness, tightness or swelling in the
      affected arm. A difference of more than 2.0 cm at any of the 4 measurement points
      may warrant treatment of the lymphedema, provided that tumour involvement of the
      axilla or brachial plexus, infection and axillary vein thrombosis have been ruled
      out. Practitioners may want to encourage long-term and consistent use of
      compression garments by women with lymphedema. One randomized trial has
      demonstrated a trend in favour of pneumatic compression pumps compared with no
      treatment. Further randomized trials are required to determine whether pneumatic
      compression provides additional benefit over compression garments alone. Complex
      physical therapy, also called complex decongestive physiotherapy, requires
      further evaluation in randomized trials. In one randomized trial no difference in
      outcomes was detected between compression garments plus manual lymph drainage
      versus compression garments alone. Clinical experience supports encouraging
      patients to consider some practical advice regarding skin care, exercise and body
      weight. [A patient version of these guidelines appears in Appendix 2.]
      VALIDATION: An initial draft of this document was developed by a task force
      sponsored by the BC Cancer Agency. It was updated and revised substantially by a
      writing committee and then submitted for further review, revision and approval by
      the Steering Committee for Clinical Practice Guidelines for the Care and
      Treatment of Breast Cancer. SPONSOR: The steering committee was convened by
      Health Canada. COMPLETION DATE: October 2000.

PMID- 11332313
TI  - Osteonecrosis of the femoral head in men following short-course corticosteroid
      therapy: a report of 15 cases.

PMID- 11332314
TI  - Effectiveness of follow up-letters to health care providers in triggering follow
      up for women with abnormal results on Papanicolaou testing.

PMID- 11332315
TI  - Specialization and cancer: words with too many meanings should be handled with
      care.

PMID- 11332316
TI  - Keeping breast cancer guidelines current.

PMID- 11332317
TI  - Clinical practice guidelines for the care and treatment of breast cancer:
      adjuvant systemic therapy for node-negative breast cancer (summary of the 2001
      update).

PMID- 11332318
TI  - Inner city health.

PMID- 11332319
TI  - Bioethics for clinicians: 22. Jewish bioethics.
AB  - Jewish bioethics in the contemporary era emerges from the traditional practice of
      applying principles of Jewish law (Halacha) to ethical dilemmas. The Bible
      (written law) and the Talmud (oral law) are the foundational texts on which such
      deliberations are based. Interpretation of passages in these texts attempts to
      identify the duties of physicians, patients and families faced with difficult
      health care decisions. Although Jewish law is an integral consideration of
      religiously observant Jews, secularized Jewish patients often welcome the wisdom
      of their tradition when considering treatment options. Jewish bioethics
      exemplifies how an ethical system based on duties may differ from the secular
      rights-based model prevalent in North American society.

PMID- 11332320
TI  - Rheumatology: 11. Evaluation of the patient with pain all over.

PMID- 11332322
TI  - Canadian MDs help US "drug refugees" bypass high prices.

PMID- 11332321
TI  - Homelessness and health.
AB  - Homelessness affects tens of thousands of canadians and has important health
      implications. Homeless people are at increased risk of dying prematurely and
      suffer from a wide range of health problems, including seizures, chronic
      obstructive pulmonary disease, musculoskeletal disorders, tuberculosis, and skin
      and foot problems. Homeless people also face significant barriers that impair
      their access to health care. More research is needed to identify better ways to
      deliver care to this population.

PMID- 11332323
TI  - Quebec may tighten Medicare eligibility.

PMID- 11332324
TI  - Evidence-based medicine in the palm of your hand.

PMID- 11332325
TI  - Out-of-pocket health care costs.

PMID- 11332326
TI  - Gene abnormalities may lead to multiple system defects for heart patients.

PMID- 11332327
TI  - Winter needn't be the SAD season.

PMID- 11332328
TI  - Renal cell carcinoma and malignant phase hypertension.
AB  - Many cross-sectional and follow-up studies of large numbers of patients with
      hypertension have demonstrated an increased prevalence and mortality from renal
      cancer. We report the details of three patients with renal cell carcinoma from a
      series of 254 consecutive patients with malignant phase hypertension, an excess
      over the expected number reported from several large published series with non
      malignant hypertension. In view of this excess we investigated the prevalence of
      hypertension in a series of 192 consecutive patients who presented with a
      diagnosis of renal cell carcinoma, in comparison with a local unselected
      population screening survey. Hypertension was found in 43% of the renal carcinoma
      patients and 20% of the local population, also a clear excess. The mechanism of
      the association between renal cancer and malignant and non-malignant hypertension
      is unclear.

PMID- 11332329
TI  - Relationship between alcohol consumption, ambulatory blood pressure recordings
      and left ventricular mass.
AB  - The relationship between alcohol consumption, blood pressure and left ventricular
      mass remains uncertain. A detailed alcohol intake history, clinic blood pressure
      measurements, 24-h ambulatory blood pressure recordings and measurements of left
      ventricular mass using magnetic resonance imaging (MRI) were performed in 98
      males aged 47.9 +/- 9.7 years, 20 of whom were receiving antihypertensive
      monotherapy. Alcohol consumption (median intake 315 g/week, range 0-2050) was
      significantly related to supine systolic clinic blood pressures (beta = 0.20, p =
      0.05) but not to clinic supine diastolic blood pressures (beta = 0.12, p = 0.25),
      24-h blood pressures (systolic: beta = -0.03, p = 0.75; diastolic beta = -0.05, p
      = 0.60), awake blood pressures or sleeping blood pressures. Alcohol consumption
      was not related to left ventricular mass index (beta = -0.05, p = 0.59). Left
      ventricular mass was strongly related to mean 24-h systolic blood pressures (beta
      = 0.28, p = 0.01), mean awake and sleeping systolic blood pressures, and less
      strongly to clinic systolic blood pressures (beta = 0.23, p = 0.03). These
      results were not significantly altered by adjusting for age, smoking, body mass
      index or alcohol intake, or by excluding the 20 men who were receiving
      antihypertensive therapy. The results of this study suggest that alcohol
      consumption at levels commonly encountered in the community is not an important
      predictor of left ventricular mass index in men, either via direct effects or by
      indirect effects on blood pressure.

PMID- 11332331
TI  - Role of ambulatory blood pressure monitoring in the assessment and prognosis of
      patients with borderline hypertension.
AB  - The role of ambulatory blood pressure (ABP) monitoring in the assessment of
      mild/borderline hypertension (BHT) is unclear. The aim of this study was to test
      the hypothesis that measurement of ABP in borderline hypertensives differentiates
      patients with true mild hypertension from those with isolated clinic hypertension
      (raised office BP but normal ABP) and that a raised ABP identifies a subgroup who
      are more likely to progress to and require treatment over 1 year. Consecutive
      untreated patients with BHT (n = 127, 44 +/- 13 years, 45% male) were divided
      into two groups according to awake ABP: Group 1 (normal ABP < or = 136/86, n =
      48), and Group 2 (abnormal ABP > 136/86, n = 79). Left ventricular mass index
      (LVMI) was greater (116 +/- 30 vs 101 +/- 25 g/m2, p < 0.01) and the proportion
      of patients with an increased LVMI was significantly higher (34% vs 17%, p =
      0.05) in Group 2. During 1 year of follow-up, significantly more patients in
      Group 2 (34%) required antihypertensive treatment compared with Group 1 (8%, p =
      0.01). ABP monitoring usefully discriminates between patients with true BHT and
      those with isolated clinic hypertension. An elevated awake ABP on initial
      assessment is associated with a higher LVMI and a greater likelihood of
      progression to moderate hypertension requiring pharmacological treatment.

PMID- 11332330
TI  - Myocardial insulin-mediated glucose uptake and left ventricular geometry.
AB  - Whole-body insulin sensitivity has been shown to be impaired in subjects with
      increased left ventricular relative wall thickness (RWT) and in hypertensive
      subjects with left ventricular hypertrophy, but the relation between myocardial
      insulin sensitivity and RWT or left ventricular mass index (LVMI) in normotension
      is not known. We measured myocardial and skeletal muscle glucose uptake with
      [18F]fluorodeoxyglucose and positron emission tomography during hyperinsulinemic
      euglycemic clamp in nine men with wide ranges of echocardiographic RWT and LVMI.
      The subjects were male, 72-74 years old, normotensive and free from medication or
      history of heart disease. RWT correlated inversely with skeletal muscle glucose
      uptake (r = -0.69, p = 0.04), borderline significantly directly with myocardial
      glucose uptake (r = 0.62, p = 0.07), and directly with the ratio between
      myocardial and skeletal muscle glucose uptake (r = 0.77, p = 0.02) during
      hyperinsulinemic euglycemic clamp. LVMI was not related to insulin-mediated
      myocardial or skeletal muscle glucose uptake or the ratio between myocardial and
      skeletal muscle glucose uptake. In conclusion, RWT was inversely related to
      insulin sensitivity in skeletal muscle and borderline significantly directly
      related to insulin sensitivity in the myocardium in healthy normotensive elderly
      men, whereas LVMI was not related to myocardial or skeletal muscle insulin
      sensitivity.

PMID- 11332332
TI  - Blood pressure levels in treated hypertensive patients in general practice in
      Norway.
AB  - The aim of this study was to examine the blood pressure (BP) levels in patients
      treated for essential hypertension in 1816 patients in general practice in
      Norway. The study was based on an optical readable questionnaire filled out by
      the physician including information about systolic (S) and diastolic (D) BP,
      gender, age, body weight, smoking habits and all pharmaceutical treatment given.
      Sixty-four per cent of the patients were treated with one antihypertensive drug.
      Only 22.3% of the women and 30.7% of the men (p < 0.05) had BP < or = 140/90
      mmHg. When BP < 160/95 was used as criterion for BP control, the fraction of
      patients was 50%. The fraction of patients with DBP < or = 80 mmHg was 26% in the
      whole group of patients. DBP < or = 90 mmHg was achieved in 74% and SBP < or =
      140 mmHg in 30% of the patients. The BP control was less in women and in patients
      above 60 years of age. Patients on combination therapy were no better controlled
      than those on monotherapy. Based on our results, the proportion of hypertensive
      patients on drug treatment with insufficient BP control is too high. Efforts
      should be made to improve the medical treatment of hypertension in general
      practice in Norway.

PMID- 11332333
TI  - The discovery of dopamine rewarded--the Nobel Prize in Physiology and Medicine
      2000.

PMID- 11332334
TI  - The effect duration of candesartan cilexetil once daily, in comparison with
      enalapril once daily, in patients with mild to moderate hypertension.
AB  - OBJECTIVE: To determine the antihypertensive efficacy, effect duration and safety
      of the angiotensin II type 1 receptor blocker candesartan cilexetil and the
      angiotensin converting enzyme inhibitor enalapril once daily in patients with
      mild to moderate hypertension. METHODS: A multicenter, randomised, double-blind
      parallel group study was performed in Finland, France, the Netherlands, Spain and
      Sweden. Three-hundred-and-ninety-five men and women in the age range 20-80 years
      with primary hypertension were randomised to an 8-week double-blind treatment
      period with either candesartan cilexetil 8-16 mg or enalapril 10-20 mg once
      daily, with forced dose titration after 4 weeks. Non-invasive ambulatory blood
      pressure was measured for 36 h at baseline and after 8 weeks. The primary
      efficacy variable was the change in mean diastolic and systolic ambulatory blood
      pressure 22-24 h post-dose. RESULTS: There was a significant difference in the
      adjusted mean difference for the change from baseline to week 8 between
      candesartan cilexetil and enalapril 22-24 h post-dose by -3.5 mmHg (95%
      confidence interval, CI: -6.8 to -0.3 mmHg; p < 0.032) in ambulatory systolic
      blood pressure and -3.0 mmHg (95% CI: -5.1 to -0.8 mmHg; p < 0.008) in ambulatory
      diastolic blood pressure. There was a significant difference in adjusted mean
      daytime ambulatory blood pressure 24-36 h post-dose by -4.2 mmHg (95% CI: -6.8 to
      -1.6 mmHg; p < 0.002)/-3.5 mmHg (95% CI: -5.1 to -1.8 mmHg; p < 0.001). Both
      drugs were generally well tolerated. CONCLUSION: The results of the present study
      suggest that advantages may be attributed to the use of candesartan cilexetil, as
      compared to enalapril in the treatment of patients with essential hypertension.
      In comparison with enalapril 20 mg, candesartan cilexetil 16 mg more effectively
      lowered blood pressure at trough and in particular on the day following the day
      after the last dose.

PMID- 11332335
TI  - Addressing those two that go together: the angiotensin II receptors and their
      role in blood-flow regulation.

PMID- 11332336
TI  - [Skin aging].
AB  - The skin aging is the result of the association of seven factors; chronological
      factor, genetic factors, exposure to ultraviolet rays (photodamage), behaviour
      factors, endocrinous, catabolics and mechanics factors. The treatment combine sun
      protection measures, topical treatment, dermatological and surgical techniques
      (peelings, resurfacing laser, injections of collagen, botulic toxin...). The
      authors intend to study clinical and anatomy-physiology aspect of skin aging, as
      well as different treatments.

PMID- 11332337
TI  - [The aging lung: structural and functional modifications related to aging].
AB  - Ageing is accompanied by numerous structural and functionnel pulmonary
      modifications. Structural modifications concern the thoracic well- and the
      broncho-pulmonary system. Functionnel modifications are numerous and concern
      specially respiratory changes, pulmonary circulation, adaptation to exercise,
      biochemical system and pulmonary defences. The knowledge of these modification
      allows better care of the aged affected by respiratory diseases.

PMID- 11332338
TI  - [Epidemiologic data in renal lithiasis in adults].
AB  - The morpho-costitutional analysis of 574 urinary lithiasis emitted by tunisean
      adults permitted to define an epidemiology's profile. This resemble to the
      epidemiology's profile of under-developed conry: Amore raised frequency of the
      renal lithiasis at the man than at the woman with a sec ratio of 2.4. An average
      age of +14 years with a peak to 4th decade in 2 sexes. The upper localitation of
      the calculi is founded in 94% cases. The frequency of the relapses, the mode of
      expulsion and the size of calculi are different of those published in the
      literature. Probably because the time of study which last 4 years is too short,
      so it don't enable us to find a result like the literature. The surgery is the
      mode of most frequent elimination (51%). This s du to the presence great size
      calculi in our population and to the recent introduction of the lithotritie in
      our country.

PMID- 11332340
TI  - [Influence of age at operation on the results of aortic coarctation surgery].
AB  - The aim of our study is to determine the ideal operative age of aortic
      coarctation. 30 patients (20 male and 10 female) have had surgery for coarctation
      of the aorta between 1990 and 1998. Mean operative age is 4.5 years (range 2
      months and 13 years). Crafoord technique was performed in 23 cases, modified
      Crafoord technique in 3 cases, Waldhausen operation in 3 cases and coarctectomie
      with insertion of a prosthetic material in one case. A post-coarctectomy syndrome
      was noted in one case. There were no early deaths. The mean follow-up period is
      4.5 years. 8 patients were noted to have late systemic hypertension (26.5%). It
      is more frequent in patients that have been operated after the age of 5 years
      (43%). One patient has had a recoarctation (3%). No late death was noted. 4
      patients had to undergo a reoperation for cardiac associated anomalies.

PMID- 11332339
TI  - [Cerebromeningeal tuberculosis: 15 pediatric cases].
AB  - Fifteen patients (9 girls and 6 boys) with different forms of cerebromeningeal
      tuberculosis (meningitis: 13 cases, tuberculoma: 2 cases) was reported. Their
      mean age was 6 years (4 months to 14 years). The initial diagnosis was difficult.
      Half patients had meningism, abnormal mental state and defects signs. The
      cerebrospinal fluid (CSF) leukocyte count was > 20/mm3, protein > 1 g/l (66%) and
      glucose < 2.2 mmol/l (80%). BK was isolated in 7 patients. Five patients (33%)
      died. Major neurological sequelae developed in 5 patients and 5 patients
      completely recovered. Factors predicting fatal outcome and permanent sequelae
      were: diagnosis delay, altered level of consciousness, hypotrophy and low glucose
      level in CSF.

PMID- 11332342
TI  - [Acute lymphoblastic leukemia with Philadelphia chromosome: eight case reports].
AB  - Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) is an
      aggressive form of acute leukemia that children ALL. Between 1991 and 1998, eight
      cases Ph+ ALL (7 males and one female) were diagnosed in our institution by
      successful cytogenetic studies. Median age was 37 years (range, 1-60 years).
      Leukocyte count was more than 50 x 109/l in 5 cases. According to the French
      American-British (FAB) criteria, six patients were classified L1 and two L2. The
      Ph+ as sole anomaly was seen in 2 patients (25%), while additional chromosome
      changes were observed in 6 cases. Complete remission was achieved in 5 cases
      (62%) and relapse was observed in all cases? The 2-year survival rae was 25%
      confirming the worse prognosis of this leukemia when treated with standard
      chemotherapy.

PMID- 11332341
TI  - [Value of maximum expiratory volume per second and peak expiratory flow
      monitoring in asthma. 77 patients].
AB  - A retrospective study was conducted on a sample of 77 subjects to assess the
      interest of computerized flowmeter "one-flow" in the diagnosis and follow up of
      asthma. 77 patients and a control group matched for age and sex, measured four
      times by day, the forced expiratory volume in one second as well as the peak
      expiratory flow during 15 to 30 days. The monitoring of these two variables
      allowed to participate to the exclusion from the study of fifteen patients whose
      asthma diagnosis was informed. It also allowed the confirmation of four
      occupational asthma. Concerning the adherence of the treatment by patients, the
      conclusion of the study showed that 47% of patients modified their treatment at
      home without consulting their doctors, 38% resorted to their doctor and only 3%
      resorted to the emergencies.

PMID- 11332343
TI  - [Sweet's syndrome].
AB  - Sweet's syndrome or acute febrile neutrophilic dermatosis is relatively frequent.
      It can be isolated or associated to other diseases, particularly, inflammatory or
      autoimmune diseases, lymphoproliferative or malignant disorders. In this
      retrospective study, we report 10 cases of Sweet's syndrome recorded over a 42
      months period. The female predominance was net (9 womens for 1 man). The mean age
      was 45 years. The diagnosis was established, in all cases, on clinical,
      biological and histological criteria. The lesions occurred most commonly on legs
      (9 cases). The failure of antibiotics has been noted in all patients, and
      colchicine has been demonstrated efficient in 6 patients. Our study confirms the
      interest of cutaneous biopsy in case of papulo-nodular lesions which has not
      respond to antibiotics.

PMID- 11332344
TI  - [Hysterectomies in tropical zones: experience of one African maternal health
      service. 141 cases in Burkina Faso].
AB  - We conducted a retrospective study of all hysterectomies performed in our setting
      over a two year period (1995-1996). The objective was double: define the
      indications and precise the outcome. A total of 141 cases were recorded. The main
      characteristics of the patients were the following: a mean age of 38 years, mean
      gravidity and parity of 5 and an average number of living children of 3.
      Hysterectomy was performed by the abdominal route in 86.52% of the cases. The
      main indications were: uterine rupture (39.71%), uterine myoma (25.53%), genital
      prolapse (19.89%) and cervix cancer (7.09%). Adnexectomy was associated in 51
      cases and it was bilateral in 22 cases. The following complications occurred: 5
      deaths, 8 wound abcess, 2 bladder injury, 1 ureter injury and 1 case of post
      operative hemorragea.

PMID- 11332345
TI  - [Enecphalocele: 26 retrospective cases at the Maternal and Neonatal Center of La
      Rabta, Tunis].
AB  - Encephalocel is leff frequent than spina bifida and anencephalia. Its incidence
      is 0.25@1000 births. It concern as much female than male. This neural defect is
      frequency associated to others malformations face (20%) squelette (17%), kidney
      (13%). In our study the ultra sound is performant in 82% of the cases.
      Encephalocel is still a lethal and severe abnormality.

PMID- 11332346
TI  - [Mesenchymatous chondrosarcoma of the superior maxillary bone. A case report].
AB  - The authors report a new case of mesenchymal chondrosarcoma (MCS), occurring in
      the upper jaw bone of a 19 year-old woman. Radiographic picture in the bone shows
      an aggressive osteolytic tumor suspect of malignancy. An incisional biopsy was
      practiced and the histologic examination has confirmed the diagnosis of MCS.
      Treatment have consisted of a large resection of maxilla with additional
      irradiation therapy. The postoperative course was marked by recurrence of the
      lesion one year later.

PMID- 11332347
TI  - [Subcapsular liver hematoma. Two case reports and review of the literature].
AB  - The authors report two cases of complicated toxaemia by subcapsular haematoma of
      liver in the gynaecology obstetrics ward of the Mongi Slim university hospital in
      Marsa, Tunisia during six years. The diagnostic was made after delivery in all
      cases. Evolution was been favourable only in one case, the other is complicated
      by superinfection which required surgical draining. The literature review
      determiner the poor prognosis of the subcapsular haematoma of the liver.

PMID- 11332348
TI  - [Complete repair of a corrected transposition of the great vessels by double
      switch. A case report].
AB  - We report the observation of a female patient with a corrected transposition of
      the great arteries, ventricular septal defect and complete atrio-ventricular
      block. This complex cardiac disease originated heart failure and was discovered
      at the age of 4 months. This baby has been operated at the age of 7 months, in
      April 1998. She had a complete repair by the double switch, closure of the
      ventricular septal defect and implantation of a permanent pace-maker. Short term
      results are favorable. Total repair of the corrected transposition of the great
      arteries is currently possible thanks to the recent technique of the double
      switch. It remains a difficult operation but with satisfactory short term
      results.

PMID- 11332349
TI  - [Venous thromboembolic disease: risk factors and hemostatic anomalies].

PMID- 11332350
TI  - [Diagnosis and treatment of deep venous thromboses: towards ambulatory
      management].

PMID- 11332351
TI  - [Treatment of deep vein thrombosis: from fraxiparine to fraxodi].

PMID- 11332352
TI  - Factors influencing the degree and outcome of acute beta-blockers poisoning.
AB  - Since severe and fatal poisoning with beta-blockers due only to beta-receptor
      blockade is unlikely, a prospective and partly retrospective analysis of 67
      patients with beta-blockers poisoning was done in five-year period in order to
      determine the factors influencing the degree and outcome of acute poisoning.
      According to pharmacological properties of drugs, the patients were divided in
      groups: group I--50 patients with propranolol, group II-A--10 patients with
      atenolol and group II-B--7 patients with metoprolol poisoning. Electrocardiogram
      (ECG), 24-h ECG monitoring, toxicological screening (determination of beta
      blockers in blood, urine and lavage by high performance liquid chromatography)
      and biochemical analysis were performed in all patients. Significantly smaller
      number of patients with serious poisoning was observed in group II-B. Patient's
      age did not correlate with the degree of poisoning, but significant correlation
      was found between preexisting disease, ingested dose and the time elapsed before
      the treatment started. Analysis of pharmacological properties showed that
      membrane stabilizing activity and lipophilicity of the drug might be the
      important determinants of the toxicity, while the role of cardioselectivity was
      lost in an overdose.

PMID- 11332353
TI  - The role of phospholipase A2 in the pathogenesis of respiratory damage in
      hemorrhagic necrotizing pancreatitis--assessment of a new experimental model.
AB  - The new experimental model has been set as a standard with the purpose to explore
      and analyze the role of phospholipase A2 in predicting the severity of acute
      pancreatitis with specific interest for the onset of hemorrhagic necrotizing
      pancreatitis and pleuropulmonary complications. The experiments were performed on
      dogs (n = 25), and acute pancreatitis was induced with the injection of 10%
      sodium-taurocholate into pancreatic duct. Four experimental groups of animals
      were formed, so that 2 groups had lymph held by draining the thoracic duct. In
      the other two groups, the lymph had been put into system circulation, so that the
      nylon bag was set around the pancreas in order to prevent pancreatic juice to be
      spilt into abdominal cavity. The analyses of the levels of amylase, lipase,
      pancreatic amylase and phospholipase A2 in of serum, lymph and exudate were
      performed. The positive correlation was found between increased concentration of
      phospholipase A2 in serum and reduction of partial pressure of oxygen and pH of
      blood and the degree of severity of respiratory failure. The speed and intensity
      of development of the acute hemorrhagic necrotizing pancreatitis, as well as the
      severity of pulmonary complications might be estimated upon the of increase of
      the levels of phospholipase A2 in serum and lymph. This experimental model
      enables the studying of pathogenesis of acute pancreatitis and systemic
      complications.

PMID- 11332354
TI  - [Analysis of a 4-year follow-up of the results of kidney transplantation from
      living related donors].
AB  - The aim was to present a four-year experience in living related kidney
      transplantation. A total of 43 patients (9 females and 34 males) were enrolled in
      this study. The standard triple immunosuppressive therapy (steroids, azathioprine
      and cyclosporine) was administered in 19 (44.1%) patients, and in 20 (46.5%)
      mycophenolate mophetil in daily dose of 2 g instead of azathioprine. In 5 (14.2%)
      patients with high immunological risk and delayed graft function was administered
      antithymocite globulin in duration of 7-14 days, prophylactically. In 3 (6.97%)
      patients graft loss was caused by vascular complications and in 1 (2.32%) by
      infection as the complication. During the first post-transplantation year acute
      rejection was noticed in 8 (34.7%) patients and in 3 (37.5%) it was steroid
      resistant. The graft loss was never caused by acute rejection. Six-months graft
      survival was noticed in 91.1% patients and one-year graft survival in 88.4%
      patients. One-year patient survival was 100%. Short term results in living
      related kidney transplantation are excellent and nowadays, due to improvement in
      immunosuppressive therapy, the success in this type of kidney transplantation is
      mainly limited by surgical and infective complications.

PMID- 11332355
TI  - [Association of manifestations of acute stress disorder and acute cerebrovascular
      disease].
AB  - The study comprised 32 patients who were with clinically, laboratory and
      neuroradiologically confirmed associated occurrence of acute stress disorder and
      stroke. All the examinees were civilians exposed to war stress, so it could be
      directly designated as the cause of acute stress disorder and indirectly denoted
      as a trigger of cardiovascular, endocrine and cerebrovascular disorder that
      brought to stroke.

PMID- 11332356
TI  - [Therapeutic value of antioxidants and calcium channel blockers in patients in
      the acute phase of closed head injuries].
AB  - Knowing that uncontrolled calcium signalization with excessive production of
      reactive oxidative matters is present in case of neurotrauma, aim of the
      investigation was to establish therapeutic value of combined administration of
      antioxidants (AO) and calcium channel blockers (CCB) in patients with closed head
      injury (CHI). Investigation comprised 120 patients with CHI who received AO
      (vitamins C and E) parenterally during 10 days and CCB (nimodipine), and control
      group was comprised of 60 patients with CHI who did not receive these medicinals
      in therapeutic program. We have established the influence of the therapy on
      neurologic and functional deficiency and consciousness disorder, respectively.
      Results of the investigation confirmed better recovery of all three observed
      parameters (degree of neurologic deficiency, degree of functional deficiency and
      consciousness disorder) in a group of patients receiving AO and CCB, which was
      statistically significant. It can be concluded that the administration of AO and
      CCB in patients with CHI in the acute phase should be included into therapeutic
      program of this significant clinical syndrome.

PMID- 11332357
TI  - [Usefulness of the lumbar support cushion for pilots of military helicopters].
AB  - The aim of our study was to evaluate the possibility of prevention of local
      reflex hyperactivity of the paraspinal muscles as the one of causes of low back
      pain during long-term sitting in forced position. We examined eight pilots, with
      low back pain during and after flying tasks. In improvised conditions, sitting
      position was performed in an equal term as the real, with and without lumbar
      support cushion. The pause between two examinations was 24 to 48 hours. Activity
      of paraspinal muscles was measured by surface electromyography, just after the
      ended sitting position. In six out of eight our subjects was decreased EMG
      activity after using the lumbar cushion, in comparison to values registered after
      sitting without cushion in comparison to values registered after sitting without
      cushion. We concluded that reflex hyperactivity of the paraspinal muscle could be
      prevented with lumbar cushion which, on the other hand can improve working and
      operative capabilities of the pilots, and simultaneously is rational from
      economic point of view.

PMID- 11332358
TI  - [The attitude of soldiers toward military service].
AB  - Due to the formation of the new state--SR Yugoslavia and transformation of armed
      forces as well as social-political changes which resulted in changes of
      fundamental social values, the aim of this study is to analyze the factors
      influencing the attitudes of the youths to the military service in Yugoslav army.
      The sample consisted of 200 adapted (group A) and 400 nonadapted (group NA)
      soldiers. The applied instrument was the Adjustment questionnaire. The attitude
      to the military service has two poles: negative included 72.5% soldiers of group
      NA and positive included 78% soldiers of group A. Between two poles there were
      27.5% soldiers of NA and 22% soldiers of group A who were ambivalent to the
      military service. It is concluded that the attitude to the military service of
      the group A soldiers was influenced by their parents, but of the group NA was
      not.

PMID- 11332359
TI  - [General characteristics of suicide in the region of Kragujevac].
AB  - A complete record of all suicides (regardless the outcomes) was done for the five
      year period (1991-1995). The research reviewed the factors influencing suicidal
      behavior, with special reference to socio-medical and meteorological ones. The
      data were obtained from the Ministry of internal affairs of Serbia, medical
      records from the Psychiatry Center (Clinical center Kragujevac), and SINOP
      reports from the meteorological station in Kragujevac. Structure of the suicides
      with lethal outcome showed extremely great percentage (60.2%) of the unemployed.
      Significant difference, at the level of 0.01, was found between age structure and
      suicide. There was somewhat younger age among tentamen suicide (41.23 years) in
      comparison to suicides with lethal outcome (59.50 years). Likewise, a significant
      difference between autochthons and newcomers, in favor of the latter was found.
      Stable, warm and sunny weather was the greater suicidal risk than the other
      biotrophic weather conditions. Based on these results, there is a possibility of
      tracking down the individuals at risk and timely prediction of suicide. In order
      to prevent this significant socio-medical problem.

PMID- 11332360
TI  - [Animal models of depression].

PMID- 11332361
TI  - [Specific therapy of methanol and ethylene glycol poisoning].

PMID- 11332362
TI  - [Heterogeneity of hypertension: why do patients respond differently to
      antihypertensive therapy?].

PMID- 11332363
TI  - [Immunophenotype and functional characteristics of lymphocytes in patients with
      common variable immunodeficiency].

PMID- 11332364
TI  - [Ameloblastic fibro-odontoma].
AB  - Ameloblastic fibro-odontoma is a rare malformation which is classified in group
      of odontomas, such as simplex and compound odontomas. A lesion usually develops
      asymptomatically in the first or the second decade of life, near the non-erupted
      or displaced tooth, consisting of numerous small tooth-like components. This is a
      case report of a 10 years old boy with tumor-like lesion in the angle of
      mandibula in whom was confirmed ameloblastic fibroodontoma after the operation
      and histological examination. Considering the growth potential and its clinical
      features, ameloblastic fibroodontoma requires adequate surgical treatment.

PMID- 11332365
TI  - [Multiple intrathoracic compression syndrome of thyroid etiology].
AB  - The aim of this article is to present a case report of multiple compression
      syndrome caused by intrathoracic thyroid papillary carcinoma and the review of
      compression intrathoracic syndrome of thyroid etiology. In our patient were
      confirmed: tracheal and esophageal deviation and compression, superior vena cava
      syndrome, downhill varices, chylothorax, pericardial effusion, compression of the
      left subclavian artery, unilateral lesion of recurrent and phrenic nerve, and
      brachial plexopathy. This was a unique case with multiple compression syndrome
      out of 2000 patients surgically treated for all kinds of thyroid diseases.
      Intrathoracic goiter can cause all the known symptoms and syndromes of
      intrathoracic compression with a possibility of rapid deterioration and fatal
      outcome.

PMID- 11332366
TI  - [Visual hallucinations in mentally healthy persons--the Charles Bonnet syndrome].
AB  - Charles Bonnet syndrome is described as complex visual hallucinations that are
      known to occur in individuals with impaired vision whose emotional and
      intellectual functions are within normal range. This paper presents a case of a
      82 years old woman who experienced an individual hallucinatory episode during
      three days: seeing, alert and with her eyes open, different figures and images,
      static and moving in lovely colors that disappeared with closing her eyes and
      appeared as new with opening it. The diagnostic procedure comprised EEG and
      ophthalmologic examination. Vitamins and hemorrheologically active therapy were
      administrated and accompanied with explaining the nature of her problem.

PMID- 11332367
TI  - [Nobel prize-winning surgeons--part 1].

PMID- 11332368
TI  - [Visits to school physicians].

PMID- 11332369
TI  - [When a child dies].

PMID- 11332370
TI  - [Foot-and-mouth disease].

PMID- 11332371
TI  - [Physician with responsibility for the patient].

PMID- 11332372
TI  - [Chronically ill and disabled children--a challenge for health services].

PMID- 11332373
TI  - [Ambulance service].

PMID- 11332374
TI  - [Ambulance response intervals in connection with cardiac arrest in Oslo].
AB  - INTRODUCTION: An important factor determining survival after out-of-hospital
      cardiac arrest is how fast the ambulance personnel can reach the patient.
      MATERIALS AND METHODS: In a two-year period between 1996 and 1998, all ambulance
      calls to patients with out-of-hospital cardiac arrest in Oslo were evaluated. Of
      1,026 cardiac arrests, 130 were excluded because of missing data. RESULTS: The
      median ambulance response interval was 7.2 min (5.7-9.0 as 25-75% percentiles).
      There was a tendency to shorter response intervals to the central parts of Oslo
      with medians between 3 and 4 min, while 14 more peripheral boroughs had median
      response intervals over 8 min. Of the 627 cases where the ambulance starting
      point was registered, 76% were from the only ambulance station in Oslo, located
      downtown. INTERPRETATION: In our opinion, the median ambulance response interval
      is unsatisfactory in large parts of Oslo, as a long response time gives a
      dramatically lower survival rate after cardiac arrest. A reorganisation and
      decentralization of the Oslo Emergency Medical Service System seems necessary.

PMID- 11332375
TI  - [How long does it take for an ambulance to arrive?].
AB  - BACKGROUND: There are few Norwegian recommendations for quality and efficacy of
      ambulance performance. A report commissioned by the Ministry of Health and Social
      Affairs concluded that the ambulance service was the weakest link in the chain of
      survival. The report proposed standards for response intervals in emergencies:
      90% of the population in cities and urban areas should be reached by an ambulance
      within eight minutes. In rural areas, 90% should be reached within 25 minutes.
      MATERIAL AND METHODS: This study describes the ambulance response interval for
      the 2,589 red code emergencies in the 15 municipalities in Vestfold County in
      1998, a county with a population of 208,687, or 97.5 inhabitants per square
      kilometre, with seven ambulance stations. A retrospective analysis was made of
      data for the year 1998. RESULTS: The proposed standard was not reached in any
      municipality in the county. The city of Tonsberg had the best performance, but
      even here only 48.9% of the population were reached by ambulance within eight
      minutes. The worst performance was found in the rural municipality of Tjome;
      here, only 63.3% were reached within 25 minutes. INTERPRETATION: Achieving the
      standards proposed will require a major restructuring of existing ambulance
      services.

PMID- 11332376
TI  - [Prescription of central nervous system stimulants].
AB  - BACKGROUND: The Child and Adolescent Unit at Nordland Psychiatric Hospital has
      conducted a review of the prescription practice in its region with regard to
      central nervous system stimulants. MATERIAL AND METHODS: Data were collected from
      the region's pharmacies on the type of drug, the type of medical practitioners
      prescribing them, and patients's sex, age and community of residence. RESULTS:
      The total numbers of users of Ritalin/Dexamin (methylphenidate/dextroamphetamine)
      were 199 children (under 18) and 21 adults (above 18). The male/female ratio was
      4:1, boys between 8 and 13 being the largest group. Users in the below-18 group
      constituted 0.35% of their age group in our region. Prescriptions to children
      were in 188 out of 199 cases written by child psychiatrists or paediatricians.
      Prescription patterns in the seven local hospital areas in the region were almost
      identical, with one area forming an exception. INTERPRETATION: This survey
      suggest that because of insufficient knowledge of the diagnostic criteria for
      attention deficit/hyperactivity disorders, many children with this type of
      problems do not get the treatment they may need. Adequate treatment based on
      competent diagnostic assessment is assumed to relieve distress and counteract the
      development of further problems. Similar surveys in other Norwegian regions would
      enable us to compare prescription practice nation-wide.

PMID- 11332377
TI  - [X-ray of small bowel with a probe--indications and diagnostic yield in a 10-year
      material].
AB  - BACKGROUND: We wanted to evaluate the indications for ordering small bowel enema,
      and whether specific clinical symptoms and signs are associated with the
      diagnostic yield. MATERIAL AND METHODS: Medical charts and requisition slips for
      241 patients examined with small bowel enema at Harstad Hospital from 1986 to
      1995 were reviewed. RESULTS: The most common symptom leading to small bowel
      radiography was pain, registered in almost three fourths of the patients; about
      one half reported diarrhoea. Elevated sedimentation rate and occult blood in the
      faeces were reported in one fourth of the patients. For a large proportion of the
      patients, there was no information about adequate preliminary tests in the
      medical charts. Normal radiography was reported in three fourths of the patients.
      Lesions consistent with Crohn's disease were found in one of eight patients. No
      symptoms or signs, except for elevated sedimentation rate, clearly indicate a
      positive diagnostic finding. Many requisition slips did not contain available
      information. INTERPRETATION: Small bowel radiography is performed on wide
      indications. It is difficult to make a careful selection of patients based on
      reported symptoms and signs. However, some preliminary tests are helpful and
      should be done.

PMID- 11332378
TI  - [Generalized edema following insulin treatment of newly diagnosed diabetes
      mellitus].
AB  - BACKGROUND: Generalised oedema after introducing insulin therapy is an infrequent
      complication, usually appearing when large doses are used in underweight
      patients. The pathophysiology is unclear. MATERIALS AND METHODS: Two patients
      from two different hospitals are presented by case histories. A limited
      literature search was performed. RESULTS: Patient 1. A 13-year-old girl was
      admitted with polyuria and polydipsia and a weight loss of 15 kg over six months.
      She had ankle oedema, dry scaling skin, weight 31.6 kg (2 kg below 2.5th
      centile), marked hyperglycaemia (60 mmol/l), and ketonuria without acidosis.
      After one day with insulin infusion she was treated with subcutaneous injections,
      reaching after a few days a dose of 2 U/kg/day. She gradually developed
      generalised oedema and gained 20 kg over two weeks. From day 8 after admission
      she was treated with furosemide and from day 16 also with ephedrine. S-albumin
      reached a nadir of 25 g/l. The oedema gradually disappeared. The patient was
      discharged after one month, weighing 42 kg, and with a daily insulin dose of 88
      U. Patient 2. A 14-year-old girl presented with decreased vision over a period of
      six months. She felt otherwise healthy and had no weight loss. Bilateral cataract
      and hyperglycaemia (20.7 mmol/l) were detected. There were normal serum
      electrolytes and no acidosis. After administration of insulin (increased up to
      1.5 U/kg/day) she gradually developed generalised oedema, gaining 8.5 kg over
      nine days. S-albumin fell from 36 g/l to 28 g/l. She was treated with furosemide
      and the oedema gradually disappeared in the course of one month. None of the
      patients had proteinuria, liver failure or hyperaldosteronism, but both
      experienced transient and unexplained muscle pain and neuralgic pain in the legs.
      INTERPRETATIONS: One of the cases with newly diagnosed diabetes and generalised
      oedema presented here, supports suggestions in the literature of an association
      between marked weight loss and large insulin doses. However, as shown by the
      other case presented, this association is not obligate.

PMID- 11332379
TI  - [Hyponatremic crisis--a serious side effect of diuretics in the elderly].
AB  - BACKGROUND: Treatment with thiazide diuretics is among the most frequent causes
      of severe hyponatremia. Previous reports indicate that elderly women develop more
      severe manifestations than men. The risk of developing hyponatremia increases
      when thiazide diuretics are given simultaneously with NSAIDs. MATERIAL AND
      METHODS: Three typical case-stories are presented, all cases being admitted to
      hospital with a tentative diagnosis of cerebrovascular stroke. RESULTS: It is
      shown that hyponatremia can give rise to a broad spectrum of symptoms, ranging
      from unspecific dizziness and headache to alarming neurological symptoms
      involving lethargy and severe confusion. As far as therapy is concerned, it is
      important to eliminate the cause of hyponatremia, and to carry out a controlled
      correction with isotonic or hypertonic saline. Too rapid correction can
      precipitate a serious complication called osmotic demyelination syndrome.
      INTERPRETATION: Differential diagnoses of hyponatremic conditions are discussed.
      Prescription of drugs that involve risk of hyponatremia should be preceded by a
      precise evaluation of the condition and the indication for such treatment.

PMID- 11332380
TI  - [Biventricular pacemaker treatment of patients with severe heart failure].
AB  - BACKGROUND: Biventricular pacing using a pacemaker lead located epicardially on
      the left ventricle, introduced via the coronary sinus to a coronary vein, and one
      pacemaker lead located endocardially at the apex of the right ventricle can
      resynchronize the contraction of the left ventricle. Approximately 30-50% of
      patients with severe heart failure have left bundle branch block indicating
      asynchronous contraction of the left ventricle. These patients can have a
      significant haemodynamic benefit from biventricular pacing. MATERIAL AND METHODS:
      The methods for implanting the leads are described. Biventricular pacemakers were
      implanted in five patients. RESULTS: Acceptable low thresholds for pacing the
      left ventricle were achieved. Resynchronization of the contraction of the left
      ventricle was demonstrated by using colour tissue Doppler measurements. The
      mechanisms for the haemodynamic benefit of biventricular pacing are discussed on
      the basis of our data. The first patient has been followed for 12 months. He has
      a lasting improvement in functional capacity from class IV to class II, marked
      reduction of the left ventricular size, and improvement of the left ventricular
      ejection fraction from 15% to 38%. INTERPRETATION: The results are promising for
      patients who, because of lack of donor hearts and age criteria, often cannot be
      offered heart, transplantation.

PMID- 11332381
TI  - [Atrial flutter--diagnosis and therapeutic possibilities].
AB  - BACKGROUND: Atrial flutter and atrial fibrillation are among the most common
      heart rhythm disturbances in the population, with an assumed prevalence of 1-2%.
      About 40,000-60,000 Norwegians endure such rhythm disorders, with an increasing
      occurrence in the elderly population. MATERIAL AND METHODS: Surface ECG remains
      the corner-stone for the clinical diagnosis. We describe the various mechanisms,
      clinical presentation, and diagnosis based on modern invasive
      electrophysiological methods of atrial flutter. RESULTS: The available
      therapeutic modalities for conversion during episodes and prophylaxis with drugs,
      various pacing techniques, DC conversion and surgical therapy are discussed.
      INTERPRETATION: Radiofrequency catheter ablation is the only available method to
      cure the patient in a gentle manner.

PMID- 11332382
TI  - [Radiofrequency catheter ablation of atrial flutter].
AB  - BACKGROUND: The anatomical structure of atrial flutter is now well recognized,
      and treatment with radiofrequency catheter ablation (RFA) is established. Several
      recording and ablation techniques can be applied. MATERIAL AND METHODS: An
      increasing number of patients have been treated with RFA at the Arrhythmia Centre
      at Haukeland University Hospital over the last six years. During the two-year
      period 1999 and 2000, a total of 108 procedures were performed for atrial flutter
      in a total of 84 patients. A total of 543 RFA procedures for various forms of re
      entry tachycardias were performed during the same period; hence, atrial flutter
      comprised about 20% of RFA procedures. Altogether 71 men and 14 women with a mean
      age of 57 +/- 12 years were treated. The mean history of atrial flutter had a
      duration of nine years, maximum 43 years with several hospital admissions, drug
      trials, overdrive pacing and DC conversion until they were ultimately cured with
      RFA. RESULTS: The success rate during first time treatment was 96.5%. No serious
      complications were observed. INTERPRETATION: RFA should be the treatment of first
      choice in patients with recurrent or incessant atrial flutter.

PMID- 11332383
TI  - [Modified midwife managed unit--an alternative for small birthing departments?].
AB  - BACKGROUND: The Norwegian Board of Health has proposed to divide the delivery
      units into three categories. For several of today's smaller consultant managed
      units this could lead to a reclassification into midwife managed units. MATERIAL
      AND METHODS: During 1997 and 1998 the community hospital in Lofoten has tried out
      a modified type of midwife managed unit. By a continuous selection process a high
      risk and a low risk group of gravidas were identified. The high risk group was
      referred to the central hospital in Bodo, while the low risk group was offered to
      deliver locally. RESULTS: Previously more than 90% delivered at the community
      hospital in Lofoten, while approximately 70% still delivered locally during the
      trial period. There were no deliveries during transport and no serious
      complications for mother or child caused by the new system. The community
      hospital had facilities for performing emergency caesarean sections. In 1997 nine
      caesarean sections out of 211 deliveries and in 1998 four out of 224 were
      performed. The caesarean section rate for the total population was lower during
      the trial period than over the previous five years. INTERPRETATION: A modified
      midwife managed unit could be a good alternative for small consultant managed
      units if the Norwegian Board of Health's proposal is carried through.

PMID- 11332384
TI  - [Konrad Birkhaug and the BCG vaccine].
AB  - Konrad Elias Birkhaug (1892-1980) was born in Bergen to Elisa Marie Skorge and
      Karl Anders Birkhaug, a policeman, as the sixth of their ten children. After a
      period as a laboratory assistant at Bergen Municipal Hospital, he emigrated to
      USA in 1911. He graduated from the medical school of Johns Hopkins University in
      1924. After residency in bacteriology, he became professor at Rochester
      University in 1927 and head of its laboratory of bacteriology. From 1932 to 1935
      he worked as a senior scientist at the Institute Pasteur in Paris and from 1935
      to 1945 as a fellow of the Chr. Michelsen Institute in Bergen. From 1937 he also
      headed the National Laboratory for production of BCG vaccine. After active
      involvement in the resistance movement against the Nazis during the Second World
      War, he returned to the USA in 1946 as head of the BCG laboratory of the State of
      New York in Albany. He retired in 1953 and settled in Bergen, where he died in
      1980. Birkhaug is one of the pioneers in the research on immunity reactions to
      tuberculosis infection and BCG vaccination. He is also known for producing the
      first antiserum against erysipelas, which was used from 1927 until sulphonamides
      were discovered. In addition to his international scientific publications, he
      wrote two books in Norwegian, his autobiography and a book about the German
      eradication of a small fishermen's village in Western Norway during the Second
      World War.

PMID- 11332385
TI  - [Statins--are there differences when it comes to clinical effect?].

PMID- 11332386
TI  - [Children with cancer--great progress, a lot of good news and some
      disappointments].
AB  - Each year, between 125 and 150 children under the age of 15 develop cancer in
      Norway. More than half of the children are less than five years of age at
      diagnosis. The malignancy is often of an embryonal origin and the disease
      spectrum very different from that in adults. Our progress in understanding and
      treating childhood malignancies is one of the success stories in paediatrics and
      in cancer biology and management. In the Nordic countries, about three of four
      children with cancer are cured, but the progress is different in different
      disease groups. For some malignancies, survival is close to 100%, while progress
      for other types have been much slower. However, cancer is still the main cause of
      death in children above one year of age who die of a disease. The progress has
      its price. The treatment is often intensive, with great morbidity and a definite
      mortality. Late effects are also of great concern. A more specific therapy
      targeted against the malignant cell, with less damage to normal cells, has long
      been our goal. Progress in recent years in the understanding of the malignant
      cells has now given the first definite examples that such targeted therapy may
      soon become a reality.

PMID- 11332387
TI  - [Varicella in children].
AB  - Chickenpox in childhood is a milder condition than in older patients, but serious
      and even fatal complications may occur. Complications occur especially in
      immunosuppressed individuals, but can also be seen in previously healthy
      children. In Norway, children with varicella and complications have traditionally
      been hospitalized in departments of medicine. After the new Department of
      Paediatrics was opened at Ulleval University Hospital in 1998, we have been able
      to isolate them there. This article describes our experience with these children
      and discuss our current policy guidelines. We review issues relating to
      isolation, contagiousness, prevention, complications and treatment, and
      recommendations from the literature.

PMID- 11332388
TI  - [Gastrointestinal dysmotility in children].
AB  - Motility disorders were previously impossible to penetrate, but new technics have
      made it possible to investigate these disorders. An overview of
      neurophysiological functions of the gastrointestinal tract is given, and various
      conditions representing primary and secondary motility disorders are discussed.
      Diagnostic procedures and treatment options are presented. The clinical picture
      of such disorders is demonstrated by two cases. A girl born in 1995, having
      megacystis microcolon hypoperistalsis syndrome was the first Norwegian individual
      to have an intestinal transplantation, which was performed in London, UK. A girl
      with hypoganglionosis is also reported. Since May 1998, manometry of the
      oesophagus was performed in 44 children, and pathological findings were
      demonstrated in 18 of these patients. The motoric activity of the stomach was
      investigated in 17 patients using two-dimensional ultrasound and
      electrogastrography pre- and post-prandially. Disturbed function was found in
      nine of these children. Anorectal manometry was performed in 147 individuals, and
      Hirschsprung's disease was diagnosed in four.

PMID- 11332389
TI  - [Habilitation of children--an expanding discipline].
AB  - Children with mental or physical disabilities require both general and
      specialised medical care. Since the separate health care system for mentally
      disabled people was closed down in Norway in 1991, new acts of parliament,
      parliamentary documents and guidelines have focused on improving the medical,
      educational and social services for this group. This article describes the
      organisation and some of the tools used in an interdisciplinary model. The
      challenge for us as health workers is to utilise the new diagnostic tools and the
      new treatment options. Working alongside other professions, our aim is to
      optimise the care and conditions of disabled children and their families, helping
      them closer to the goal: an independent life based on self-determination.

PMID- 11332390
TI  - [Dark skyline--developmental traits of self-experienced health during childhood].

PMID- 11332391
TI  - [Fundaments of palliative care--role of general practitioner?].

PMID- 11332393
TI  - [A mis-leading!].

PMID- 11332392
TI  - [Sjogren's syndrome].

PMID- 11332394
TI  - [Snuff and cancer].

PMID- 11332395
TI  - [Hypothermia].

PMID- 11332396
TI  - [Breech presentation?].

PMID- 11332397
TI  - [Impotence and prevalence].

PMID- 11332398
TI  - [The Baerum issue].

PMID- 11332399
TI  - Sensitivity and predictive value of criteria for p53 germline mutation screening.

PMID- 11332400
TI  - Identification of a transcriptionally compromised allele of c-MYC in a North
      American family.

PMID- 11332401
TI  - E-cadherin is not frequently mutated in hereditary gastric cancer.

PMID- 11332402
TI  - The spectrum and evolution of phenotypic findings in PTEN mutation positive cases
      of Bannayan-Riley-Ruvalcaba syndrome.

PMID- 11332403
TI  - A frameshift mitochondrial complex I gene mutation in a patient with dystonia and
      cataracts: is the mutation pathogenic?

PMID- 11332404
TI  - A common ancestor for COCH related cochleovestibular (DFNA9) patients in Belgium
      and The Netherlands bearing the P51S mutation.

PMID- 11332405
TI  - Measuring demographic group differences in cardiovascular reactivity to stress
      using a mental challenge in the laboratory: problems of interpretations.

PMID- 11332406
TI  - [About the article: "Intramuscular interferon beta-1a therapy initiated during a
      first demyelinating event in multiple sclerosis" by Jacobs LD et al].

PMID- 11332407
TI  - Anesthetic management of a patient with arthrogryposis multiplex congenita and
      limited mouth opening.

PMID- 11332408
TI  - A safety screening questionnaire for transcranial magnetic stimulation.

PMID- 11332409
TI  - Noni plant may help TB.

PMID- 11332410
TI  - Abstinence groups on the rise.

PMID- 11332411
TI  - Rebellion may cause HIV increase.

PMID- 11332412
TI  - Boys reveal sex practices.

PMID- 11332413
TI  - National Institute of Child Health and Development Conference summary: amniotic
      fluid biology--basic and clinical aspects.
AB  - This report summarizes the National Institute of Child Health and Development
      sponsored conference on amniotic fluid (AF) biology, held 28-29 September 1999,
      in Detroit, Michigan. National and international investigators with expertise in
      AF biology addressed the regulation of AF volume and composition as well as the
      clinical aspects of interpreting fetal health and well-being from AF indices. A
      major purpose of the meeting was to consider future directions and opportunities
      for basic and clinical research which focus on understanding the physiology and
      pathophysiology and providing therapeutic interventions for abnormalities of AF
      volume. To achieve this, the workshop participants addressed the current state of
      knowledge, recent scientific advances and priorities for major questions for
      which answers must be sought. The fact that it is not known whether AF volume is
      regulated or what volume-regulatory mechanisms might be involved is a major
      problem that needs addressing. In the later half of gestation, potential AF
      volume-regulatory pathways include the two major inflows into the amniotic
      compartment, i.e. fetal urine and lung liquid, and the two major outflows, i.e.
      fetal swallowing and intramembranous absorption. If AF volume is regulated, then
      this must occur through regulation of intramembranous flow, because the other
      three flows are regulated by the fetus to meet fetal needs. Regulation of AF
      composition is similarly unknown. In clinical practice, a variety of
      ultrasonographic indices of AF volume are used, but the relationships of these
      indices to AF volume have not been determined, nor have their dependency on fetal
      size, shape or position within the uterus. Further, although aberrations in AF
      volume both above and below normal are associated with increased fetal and
      neonatal morbidity and mortality, the predictive utility of the various AF
      indices remains low and there is little consensus on which is best utilized under
      conditions of oligohydramnios, normal AF volumes, or polyhydramnios. Further,
      various clinical AF therapies remain largely experimental and their optimization
      and utilization need exploration. This report is a condensation of the views
      presented by the conference participants.

PMID- 11332414
TI  - Pregnancy outcome in Hispanic patients with unexplained positive triple marker
      screening for Down syndrome.
AB  - OBJECTIVE: The objective of this study was to compare pregnancy outcomes in
      Hispanic patients with a positive serum triple marker screen for Down syndrome
      and normal fetal karyotype with Hispanic women who had a negative triple marker
      screen. METHODS: This prospective investigation involved Hispanic gravidas who
      underwent maternal serum screening. A power analysis was performed to determine
      the sample size. Fifty women with false-positive screens for Down syndrome were
      matched with a control group of 100 women with a negative screen. Adverse
      pregnancy outcomes were compared between the two groups. RESULTS: An adverse
      pregnancy outcome occurred in 14% of the study group and in 13% of controls.
      There were no statistically significant differences between the two groups in the
      incidence of preterm labor (p > 0.5), pre-eclampsia (p > 0.1), intrauterine
      growth restriction (p > 0.5), or fetal demise (p > 0.5). CONCLUSION: Hispanic
      patients with unexplained positive triple marker screen for Down syndrome do not
      appear to be at increased risk for adverse pregnancy outcomes.

PMID- 11332415
TI  - The fetal superior cerebellar vermian width in normal, growth-restricted and
      macrosomic fetuses.
AB  - OBJECTIVES: To obtain dimensions of the fetal superior cerebellar vermian width
      as a basis for further studies and for comparisons with deviation in growth.
      STUDY DESIGN: The study group included 266 normal pregnant women from 20 to 37
      weeks of gestation. Several biometric measurements were obtained throughout
      pregnancy, including the fetal superior cerebellar vermian width. Forty-three
      growth-restricted and 30 macrosomic fetuses were included in this study. RESULTS:
      A linear growth function was observed between the superior cerebellar vermian
      width and gestational age (GA) (R = 0.859; p < 0.00001; y = -4.033 + 0.416 x GA),
      transverse cerebellar diameter (TCD) (R = 0.870; p < 0.00001; y = 0.404 + 0.223 x
      TCD), biparietal diameter (BPD) (R = 0.823; p < 0.00001; y = -3.086 + 0.155 x
      BPD), head circumference (HC) (R = 0.82; p < 0.00001; y = -3.21 + 0.434 x HC),
      femoral length (FL) (R = 0.843; p < 0.00001; y = -1.75 + 0.184 x FL) and humeral
      length (HL) (R = 0.824; p < 0.00001; y = -2.691 + 0.223 x HL). The ratio between
      the superior cerebellar vermian width and the transverse cerebellar diameter
      remained constant throughout gestation. In all 43 growth-restricted and the 30
      macrosomic fetuses, the dimensions of the fetal superior cerebellar vermian width
      remained within the normal range for the indexed gestational age. CONCLUSION:
      These results provide normative data for the fetal superior cerebellar vermian
      width in various dimensions and across gestational ages. In addition, growth of
      the superior cerebellar vermis remained normal in growth-restricted as well as
      macrosomic fetuses. Therefore, cerebellar vermian growth may be used adjunctively
      as a standard against which deviant fetal growth may be compared when precise
      gestational age determination is necessary.

PMID- 11332416
TI  - Change in platelet count predicts eventual maternal outcome with syndrome of
      hemolysis, elevated liver enzymes and low platelet count.
AB  - OBJECTIVE: To profile the rates of change for platelets and lactate dehydrogenase
      (LDH) in patients with the syndrome of hemolysis, elevated liver enzymes and low
      platelet count (HELLP) to reflect and possibly predict disease severity. METHODS:
      Serial determinations of the platelet count and serum LDH were analyzed
      retrospectively for 545 patients with HELLP syndrome and 94 severely pre
      eclamptic patients. A repeated measures (mixed model) analysis of variance
      (ANOVA) was utilized to estimate the rates of change for LDH and platelets in
      each group. RESULTS: Patients who developed class 1 or 2 HELLP syndrome exhibited
      a rapid deterioration in platelet count of 45-50,000/microl per day compared to
      30,000/microl per day for class 3 and non-HELLP severe pre-eclampsia. For LDH,
      values increased at a rate of approximately 1400 IU/l per day, 600 IU/l per day,
      300 IU/l per day and 200 IU/l per day for patients with classes 1, 2 and 3 and
      for non-HELLP severe pre-eclampsia, respectively. CONCLUSION: The rate of change
      of platelets and LDH appeared to correlate well with eventual syndrome severity
      and this can be used to enhance patient assessment beyond the value of a single
      test for either laboratory parameter.

PMID- 11332417
TI  - Levels of interleukin-6 in second-trimester amniotic fluid are not predictive of
      adverse neonatal outcome.
AB  - OBJECTIVE: Elevation of interleukin (IL)-6 in the amniotic fluid (AF) during the
      second trimester is associated with increased risk of preterm deliver

PMID- 11332418
TI  - Maternal serum levels of type I and type III procollagen peptides in pre
      eclamptic pregnancy.
AB  - OBJECTIVE: To compare maternal serum levels of two markers of collagen synthesis,
      procollagen I carboxy-terminal peptide (PICP) and procollagen III amino-terminal
      peptide (PIIINP), in patients with pre-eclampsia and in controls. METHODS: PICP
      and PIIINP were measured by radioimmunoassay in maternal serum samples from
      patients diagnosed with pre-eclampsia at 32 weeks' gestation or later and in
      controls from the same period of gestation. For PICP, 37 cases and 36 controls
      were studied; for PIIINP, 12 cases and 19 controls were studied. RESULTS: Both
      PICP and PIIINP levels were significantly elevated in patients with pre
      eclampsia. PICP and PIIINP levels were, on average, 20% and 80% higher than in
      controls, respectively. CONCLUSIONS: These results are in agreement with previous
      findings that maternal serum levels of PICP and PIIINP are mildly elevated in
      patients with pre-eclampsia. These markers are unlikely to be useful in the
      prediction of pre-eclampsia.

PMID- 11332419
TI  - Sonographically estimated fetal weight percentile as a predictor of preterm
      delivery.
AB  - OBJECTIVE: To evaluate the association between relative growth restriction and
      preterm birth. STUDY METHODS: Pregnant women referred for sonographic fetal
      weight assessments between 24 and 34 weeks of gestation were studied for
      gestational age at delivery. If a patient underwent more than one study, only the
      last one was considered. Patients with delivery induced iatrogenically or with
      abnormal growth patterns due to known pathology, such as maternal diabetes or
      fetal congenital anomaly, were excluded. A gestational age of 37 weeks or less
      was considered preterm and a gestational age of more than 37 weeks at delivery
      was considered term. Fetal weight estimation was obtained by Hadlock's formula
      based on biparietal diameter, femur length, and head and abdominal
      circumferences. The estimated fetal weight percentile was computed according to
      William's tables. Mean gestational age and incidence of preterm delivery for each
      fetal weight percentile between 1 and 100, at increments of 10, were calculated.
      The mean estimated fetal weight percentile, biparietal diameter, femur length,
      head circumferences and abdominal circumferences of preterm and term patients
      were compared. RESULTS: Among the 419 patients who met the inclusion criteria,
      duration of gestation was significantly shorter in fetuses with low estimated
      fetal weight percentile. The risk of preterm birth was 49% in fetuses of less
      than the 40th birth-weight percentile compared with a risk of 20% in fetuses of
      more than the 40th birth-weight percentile, representing a relative risk of 2.3.
      Individual fetal measurements indicate a head-sparing effect in the preterm
      group. CONCLUSION: Sonographically estimated fetal weight percentile measured
      between 24 and 34 weeks' gestation may be used as an additional and individually
      pertinent predictor of preterm birth.

PMID- 11332420
TI  - Evaluation of fetal heart monitoring in the first stage of labor.
AB  - OBJECTIVE: To evaluate the usefulness of continuous electronic fetal heart rate
      (FHR) monitoring in the first stage of labor. METHODS: A total of 814 pregnant
      women in labor without identifiable risk factors was divided into two groups. In
      group A (468 cases), continuous FHR monitoring began in the earliest phase of the
      first stage of labor (cervical dilatation < or = 4 cm), while in group B (346
      cases) it began when the cervical dilatation was > 4 cm. Initial FHR tracings
      were normal in all 814 cases. The fetal monitoring findings were analyzed at 10
      min intervals, and comparisons were made between the two groups concerning FHR
      findings and their correlation with the state of the newborns. RESULTS: No
      significant difference was found between the two groups in the incidence of
      repetitive variable decelerations (1.9% and 1.7%, respectively); sporadic
      variable decelerations (9.2% and 8.7%, respectively); persistent repetitive late
      decelerations that resulted in Cesarean section (1.1% and 1.4%, respectively); or
      sporadic late decelerations (8.3% and 8.1%, respectively). One newborn from each
      group required intensive neonatal care. CONCLUSIONS: The same tracing sufficiency
      of fetal stress was observed in the two groups. However, the manner of labor
      supervision in group B seemed to be more beneficial, because of greater maternal
      comfort, a lower necessity for personnel, lower consumption of cardiotocographic
      materials and the possibility of labor induction for more women. Since fetal
      monitoring is widely used, it is preferable to start continuous FHR monitoring
      when the dilatation of the cervix approximates 4-5 cm (second phase of the first
      stage of labor) without risk of fetal loss.

PMID- 11332421
TI  - Acute effect of exercise on blood glucose and insulin levels in women with
      gestational diabetes.
AB  - OBJECTIVE: To evaluate the effect of a single session of exercise (cycling), at
      rest (control condition) and at two intensity levels (low- and moderate-intensity
      exercise conditions), on blood glucose and insulin in pregnancy complicated by
      gestational diabetes mellitus (GDM). METHODS: A one-group repeated measures
      design was used. Women aged 18-38 with GDM, no other complications, not on
      insulin, and not exercising regularly were recruited. The women rested or
      exercised at the two intensities for 30 min and rested for 2 h after each
      session. Blood was sampled for blood glucose, insulin and hematocrit at baseline
      and every 15 min. RESULTS: There was no difference at baseline in blood glucose
      levels. The blood glucose level was significantly lower for each exercise
      condition compared to rest, and for moderate compared to low-intensity exercise
      (5.2 vs. 4.3 vs 3.9 mmol/l) at the end of exercise (30 min), and for the two
      exercise conditions compared to rest at 15 min after exercise (4.9 vs 4.4 vs. 4.0
      mmol/l). By 45 min after exercise, the blood glucose values were nearly
      identical. The area under the curve for blood glucose was significantly lower for
      low- and moderate-intensity exercise than for rest (p = 0.01). The slope of
      change in insulin among the three conditions, from baseline to the 30-min
      session, approached significance (p = 0.065). The power for that analysis was
      0.51. A sample of 23 would have been required to increase the power to 0.80.
      CONCLUSIONS: Significant declines in blood glucose level were observed during low
      and moderate-intensity exercise compared to rest. These differences were gone by
      45 min after exercise. Continued research should examine those with high body
      mass index and more pronounced hyperglycemia for further evaluation of the effect
      of exercise on blood glucose and insulin levels in women with GDM.

PMID- 11332422
TI  - Perinatal outcome following fetal single umbilical artery diagnosis.
AB  - OBJECTIVE: We report the frequency of associated congenital abnormalities in
      fetuses with a single umbilical artery as well as the sensitivity, specificity,
      positive predictive value and negative predictive value of ultrasound for
      detecting these abnormalities. We also report the pregnancy outcome of fetuses
      complicated by single umbilical artery, both isolated and with other congenital
      anomalies. METHODS: All pregnancies complicated by fetal single umbilical artery
      from 1995 to 1999 were identified. A retrospective chart review was performed on
      both the prenatal records and the ultrasound records of these pregnancies,
      determining the nature and incidence of other congenital abnormalities. Delivery
      data were collected to include gestational age at delivery, Apgar score, birth
      weight, mode of delivery, fetal gender and any complications. RESULTS: Ninety-two
      pregnancies were identified with a fetal single umbilical artery, of which
      outcome data were available for 65. Forty-eight (74%) cases were identified as
      isolated single umbilical artery. Seventeen (26%) cases had other congenital
      abnormalities. High-resolution ultrasound had 100% sensitivity and specificity
      for identifying single umbilical artery and an 85% sensitivity and 98%
      specificity for detecting other congenital abnormalities. Compared to isolated
      single umbilical artery, pregnancies complicated by single umbilical artery with
      other abnormalities had a statistically significantly increased rate of fetal
      aneuploidy, lower birth weight, preterm delivery and Cesarean delivery.
      CONCLUSION: Pregnancies complicated by fetal single umbilical artery, especially
      when associated with other congenital abnormalities, are at increased risk for
      adverse pregnancy outcome.

PMID- 11332423
TI  - Successful pregnancy outcome with cardiac and severe restrictive lung disease
      requiring mechanical ventilation: a case report and literature review.
AB  - The prognosis for pulmonary hypertension as a single entity is poor, but when it
      is superimposed on the physiological changes of pregnancy, it produces a lethal
      condition, with maternal mortality rates greater than 50%. We present a
      successfully managed case followed by a review and discussion of the available
      literature on this subject. A 24-year-old woman, a primigravida, was mechanically
      ventilated for severe restrictive lung disease. Her pregnancy required close
      surveillance of her labile cardiopulmonary status as well as fetal well-being.
      Her delivery was scheduled for induction at 34 weeks' gestation, but she required
      an emergency Cesarean section, which was productive of a healthy infant. Her
      recovery was complicated by recurrent fever. There is limited literature on
      restrictive lung disease and pulmonary hypertension with regards to their
      management during pregnancy. Nevertheless, successful pregnancy outcomes may
      result with careful multidisciplinary management.

PMID- 11332424
TI  - Mycosis fungoides in pregnancy: remission after treatment with alpha-interferon
      in a case refractory to conventional therapy: a case report.
AB  - Mycosis fungoides complicating pregnancy is rarely encountered. As it is a form
      of cutaneous T-cell lymphoma, some of the treatment options are contraindicated
      in pregnancy, and the disease may become unresponsive to safer conventional
      therapies. We report a patient who, in her third trimester of pregnancy, failed
      to respond to the treatment options available. Left with little choice, a trial
      of alpha-interferon was undertaken. The patient responded with remission, and
      prolongation of pregnancy was achieved.

PMID- 11332425
TI  - Prostate cancer screening.

PMID- 11332426
TI  - Prostate cancer screening.

PMID- 11332427
TI  - Adverse reactions and emergency contraception.

PMID- 11332428
TI  - Thick mucus hypothesis in cystic fibrosis.

PMID- 11332429
TI  - Did Celera invent the Internet?

PMID- 11332430
TI  - Paediatric emergency care in less-developed countries.

PMID- 11332432
TI  - Allergy in coronary in-stent restenosis.

PMID- 11332431
TI  - Allergy in coronary in-stent restenosis.

PMID- 11332433
TI  - Allergy in coronary in-stent restenosis.

PMID- 11332434
TI  - Shaken impact syndrome.

PMID- 11332435
TI  - Shaken impact syndrome.

PMID- 11332436
TI  - Competition for academic promotion in Italy.

PMID- 11332437
TI  - Osteoporosis and androgen-depleting drugs in sex offenders.

PMID- 11332438
TI  - Diagnosis of Oscar Wilde.

PMID- 11332439
TI  - Industry-sponsored research.

PMID- 11332440
TI  - Hunger strikes in Turkey.

PMID- 11332441
TI  - H C Bastian, Aldous Huxley, and Jonathan Osborne.

PMID- 11332442
TI  - Interleukin-10 and interleukin-10 receptor in human osteoarthritic and healthy
      chondrocytes.
AB  - OBJECTIVE: To evaluate the expression of interleukin-10 (IL-10) and interleukin
      10 receptor (IL-10R) on chondrocytes from healthy, osteoarthritic, and foetal
      cartilage from human subjects. METHODS: Articular cartilage was obtained from 12
      patients with osteoarthritis (OA) undergoing surgical knee replacement.
      Chondrocytes were isolated from the two zones of cartilage showing
      macroscopically and histologically the lowest (MIN) and highest (MAX) extent of
      osteoarthritic damage. Additional specimens of cartilage were obtained from 3
      healthy donors and 3 human foetuses. IL-10 mRNA expression was determined by a
      reverse transcriptase-polymerase chain reaction (RT-PCR). For detection of
      intracellular IL-10 protein, chondrocytes were permeabilized and then incubated
      with R-phycoerythrin (PE) conjugated rat anti-human IL-10 mAb. Cell surface IL
      10R was detected by incubation with biotinylated recombinant human IL-10; after
      washing, bound IL-10 was revealed by fluorescein (FITC) conjugated streptavidin.
      Positive chondrocytes were analysed by flowcytometry. RESULTS: IL-10 mRNA
      expression was higher in osteoarthritic than in normal chondrocytes. IL-10
      protein intracellular levels were significantly higher in MAX than in MIN
      osteoarthritic cartilage or in healthy cartilage. Cell surface IL-10R was
      expressed on osteoarthritic chondrocytes with no difference in the degree of
      cartilage damage. The highest levels of IL-10 protein and IL-10R were found in
      foetal cartilage. CONCLUSION: Human chondrocytes synthesise IL-10 and express on
      their surface IL-10R. Since IL-10 inhibits IL-1 and TNF-alpha expression, its
      upregulation in osteoarthritic chondrocytes may counteract the detrimental
      effects of these catabolic cytokines. However, the functions of IL-10 in
      cartilage may go beyond those activities established in the immunological
      setting. The high levels of IL-10 and IL-10R in foetal cartilage, an active
      growing tissue, suggest that IL-10 may play a role in controlling chondrocyte
      metabolism under physiological conditions.

PMID- 11332443
TI  - Analysis of serum CYFRA 21-1 concentrations in patients with esophageal cancer.
AB  - BACKGROUND: This study was conducted to determine the use of CYFRA 21-1 for
      patients suffering from esophageal carcinoma. MATERIALS AND METHODS: 50 patients
      with malignant, 50 patients with benign esophageal lesions, 50 healthy persons
      and 50 patients with benign lung disease were tested for CYFRA 21-1, CEA, CA 72-4
      and SCC-antigen serum concentrations. The patients with esophageal carcinoma
      underwent follow-up analysis for one year. RESULTS: CYFRA 21-1 (cut-off: 1.40
      ng/ml) showed a sensitivity for esophageal carcinoma of 46% at a specificity of
      89.3%. There was a tendency for higher serum CYFRA 21-1 concentrations in
      advanced T-stages. Correlations of CYFRA 21-1 with N or M stages could not be
      observed. The postoperative course, in terms of survival and tumor free survival
      showed significant correlation to pre-operative CYFRA 21-1 concentrations.
      Adjuvant therapy could be monitored by CYFRA 21-1 as well. Clinical tumor
      recurrence was preceded by CYFRA 21-1 elevation by 3.4 months. CONCLUSIONS: We
      recommend the use of CYFRA 21-1 in cases of esophageal carcinoma, especially in
      cases of squamous cell carcinoma.

PMID- 11332444
TI  - Validation of the screening strategy in the NIAAA "Physicians' Guide to Helping
      Patients with Alcohol Problems".
AB  - OBJECTIVE: This study was undertaken to determine the diagnostic test
      characteristics of the alcohol screening strategy recommended in the National
      Institute on Alcoholism and Alcohol Abuse (NIAAA) "Physicians' Guide to Helping
      Patients with Alcohol Problems." METHOD: A research interview was performed on
      patients who presented to one urban emergency department (N = 395; 61% women). It
      asked three alcohol consumption questions, the CAGE questionnaire, and about past
      alcohol problems. The NIAAA-recommended screen was considered positive for
      alcohol consumption in excess of 14 drinks per week or 4 drinks per occasion for
      men, or 7 drinks per week or 3 drinks per occasion for women, or a CAGE score of
      1 or greater. A sample of patients (n = 250) received the Composite International
      Diagnostic Interview substance abuse module, a gold standard interview, to
      determine lifetime or prior 12-month alcohol abuse or dependence; results were
      adjusted for verification bias. RESULTS: The prevalence of lifetime:alcohol abuse
      or dependence was 13%, for which the NIAAA strategy was 81% sensitive and 80%
      specific. The prevalence of alcohol abuse or dependence in the prior 12 months
      was 10%, for which the strategy was 83% sensitive and 84% specific. Its positive
      likelihood ratio exceeded that of the CAGE, augmented CAGE or consumption
      questions alone, and its negative likelihood ratio was the lowest. CONCLUSIONS:
      The screening strategy combining alcohol consumption and CAGE questions
      recommended in the NIAAA "Physicians' Guide" is valid, and has superior test
      characteristics compared to the CAGE alone, in this predominantly black (86%)
      emergency department population. Its brevity and simple interpretation recommend
      wider dissemination of the NIAAA "Physicians' Guide," although future research
      should examine its test characteristics in other clinical settings and with other
      populations.

PMID- 11332445
TI  - Importance of direct determination of amino acid co- and counter-transport
      stoichiometries.
AB  - The stoichiometry of amino acid transport with co- or counter-substrates of a
      given system has been found to vary with the amino acid species. This phenomenon
      has been studied directly in only a few cases, however, by measuring the fluxes
      of the substrates simultaneously. More frequently, the apparent transport
      stoichiometries of single amino acid species with co- or counter-substrates are
      estimated indirectly by thermodynamic criteria or cooperative kinetic effects.
      Unfortunately the latter indirect measures of apparent stoichiometry often yield
      different results than direct measurement of simultaneous fluxes. These
      differences often cannot be explained by uncoupled transport of one of the co- or
      counter-substrates or by other characteristics of the transport process that
      would make the direct measurement of stoichiometry inaccurate. For these reasons,
      investigators are encouraged to measure the stoichiometry of transport directly
      by measuring simultaneous fluxes of co- and counter-substrates. Indirect measures
      of apparent stoichiometry may, however, reflect important details of a transport
      mechanism even if they are inconsistent with the actual stoichiometry of
      transport.

PMID- 11332446
TI  - Syntheses of glycine and L-serine by their interconversion in the posterior
      silkgland of the silkworm, Bombyx mori.
AB  - It was observed by solution-state 13C NMR spectroscopy that a great portion of
      the 13C of [1-13C]L-serine fed to the 5th instar larvae of the silkworm, Bombyx
      mori was incorporated into C1 of glycine in silk fibroin. [1-13C]Glycine was
      detected along with [1-13C]serine in fibroin of the posterior silkgland cultured
      in a medium containing [1-13C]serine. This formation of [1-13C]glycine was
      inhibited by addition of aminopterin to the culture medium. These findings
      suggest that an active conversion from serine to glycine, which needs
      tetrahydrofolate, occurs in the posterior silkgland for fibroin synthesis.
      Moreover, the solid-state 13C CP/MAS spectrum of the fibroin prepared from
      cocoons spun by larvae fed with [13C]formate revealed that serine C3 was labelled
      specifically with 13C, suggesting that the reverse conversion from glycine to
      serine took place in the silkworm. The posterior silkgland has the ability to
      synthesize not only fibroin but also its major materials, glycine and serine.

PMID- 11332447
TI  - Effects of vitamins on hepatic nuclear binding of L-tryptophan.
AB  - This study investigated the in vitro effects of selected vitamins on nuclear L
      tryptophan receptor binding of rat liver. Our results revealed that some fat
      soluble vitamins, beta-carotene, retinyl acetate, calciferol, alpha-tocopherol,
      and Trolox, as well as some water-soluble vitamins, thiamine and riboflavin,
      acted to inhibit in vitro 3H-tryptophan binding to hepatic nuclei. On the other
      hand, pyridoxine had little or no effect. The addition of dithiothreitol, a
      protective agent for sulfhydryl groups, along with each vitamin decreased the
      vitamin's inhibitory effect on in vitro 3H-tryptophan binding to nuclei, with the
      exception of riboflavin and calciferol. The addition of L-leucine, which alone
      had no inhibitory effect on in vitro 3H-tryptophan binding to hepatic nuclei but
      when added with unlabeled L-tryptophan negated the effect of unlabeled L
      tryptophan, caused a markedly diminished inhibitory binding effect due to each of
      the following vitamins, thiamine, beta-carotene, retinyl acetate, and alpha
      tocopherol and Trolox, but no effect on riboflavin and calciferol.

PMID- 11332448
TI  - Novel N-quinonyl amino acids and their transformation to 3-substituted p
      isoxazinones.
AB  - Quinonyl amino acids are building blocks in the preparation of peptides which
      target the quinonic drug to cancer damaged area. Novel N-(3-chloro-1,4-dihydro
      1,4-dioxonaphthalen-2-yl)-alpha-amino acids la-f were prepared by direct
      substitution of 2,3-dichloro-1,4-naphthoquinone. The quinonic moiety was reduced
      by NaBH4 to yield the corresponding hydroquinones 2a-f, which in acidic
      conditions underwent internal cyclization to yield the 3,4-dihydro-2H-naphth[1,2
      b]-1,4-oxazine-2-ones (six-membered azlactones) 3a-f.

PMID- 11332449
TI  - Specific peptide inhibitors of trypanothione reductase with backbone structures
      unrelated to that of substrate: potential rational drug design lead frameworks.
AB  - By introducing cationic charge sites novel peptide lead inhibitor structures for
      trypanothione reductase have been designed using molecular modelling methods. The
      inhibitors showed reversible, linear competitive inhibition and the strongest
      peptide inhibitor to date was found to be N-benzyloxycarbonyl-Ala-Arg-Arg-4
      methoxy-beta-naphthylamide with a Ki value of 2.4 microM and a selectivity for
      parasitic enzyme (trypanothione reductase) over the host enzyme (human
      glutathione reductase) of over 3 orders of magnitude.

PMID- 11332450
TI  - Analysis of the disease course of HIV-1 by entropic chaos degree.
AB  - When a V3 sequence obtained on the n-th year after infection with human
      immunodeficiency virus type 1 (HIV-1) was supposed to change into a V3 sequence
      on the n + 1-th year, the variation between the above two sequences was analyzed
      by means of entropic chaos degree. The entropic chaos degree measures chaotic
      aspects of the dynamics causing the variation of sequence. If it is large, then
      the dynamics produces the large complexity, in other words, the variation of
      sequences becomes large. As a result, the chaos degree for the dynamics changing
      the V3 region showed the specific variation patterns throughout from the early
      stages of infection to death. That is, the variation patterns indicated that the
      entropic chaos degree is useful to measure the stage of disease progression after
      HIV-1 infection.

PMID- 11332452
TI  - Establishment of a rat hepatoma-derived cell line proliferating in D
      phenylalanine medium and expressing D-amino-acid oxidase.
AB  - A cell line (R-Y121B.DF) has been established from a cell line (R-Y121B) derived
      from a rat hepatoma line (H4-II-E). The R-Y121B.DF cells have been continuously
      cultured in a serum-free modified Eagle's minimum essential medium in which L
      phenylalanine was replaced by D-phenylalanine. They had D-amino-acid oxidase
      (DAO) activity which is essential for the growth in the medium containing D-amino
      acids. The enzyme activity of the R-Y121B.DF cells was approximately one-fourth
      of that of the rat liver. Northern hybridization using a DAO cDNA probe detected
      a hybridizing signal in the R-Y121B.DF cells and the rat liver but not in the
      parental R-Y121B and H4-II-E cells. Reverse transcription-polymerase chain
      reaction using DAO-specific primers amplified a DNA fragment of the expected size
      in the R-Y121B.DF cells but not in the R-Y121B and H4-II-E cells. This fragment
      was confirmed to be DAO cDNA by nucleotide sequencing. Western blotting showed
      that DAO protein was present in the R-Y121B.DF cells and the rat liver but not in
      the R-Y121B and H4-II-E cells. Southern hybridization showed that the DAO gene
      structure was not different among the R-Y121B.DF cells, R-Y121B cells, H4-II-E
      cells, and the rat liver. These results indicate that the R-Y121B.DF is a unique
      cell line which proliferates in the medium containing D-phenylalanine and
      explicitly expresses DAO. This line is useful for the study of DAO in vitro.

PMID- 11332451
TI  - A fast and sensitive method for measuring picomole levels of total free amino
      acids in very small amounts of biological tissues.
AB  - In the present study we describe a simple and fast method to measure the
      concentration of total free amino acids in very small amounts of biological
      tissues. The procedure described here is based on the reaction of free amino
      acids with o-phthaldialdehyde (OPA) in the presence of a reducing agent, beta
      mercaptoethanol (MET), to give a complex which can be measured by fluorescence.
      It is a very rapid process and has the same reliability as the conventional
      ninhydrin method of Moore and Stein but is about 500 times more sensitive. The
      sensitivity of the new protocol is such to permit the determination with high
      reliability of very small amounts of free amino acids at picomole levels, either
      in a standard amino acid mixture or in biological tissues, without
      chromatographic separation of the amino acids. It is particularly useful when the
      amount of the sample is very low, e.g. on a single pituitary or pineal gland of
      small animals or on single cells, such as oocytes or eggs, as well as single
      ganglions or axons of marine invertebrates.

PMID- 11332453
TI  - High-performance liquid chromatographic quantification of allysine as bis-p
      cresol derivative in elastin.
AB  - The first step in normal cross-linking in elastin is the formation of alpha
      aminoadipic-delta-semialdehyde, allysine, through oxidative deamination of
      specific peptidyl lysine by the enzyme lysyl oxidase (EC 1.4.3.13). For the
      analysis of allysine, allysine was derivatized with p-cresol. The derivatization
      was carried out by acid hydrolysis (6N HCl containing 5% (w/v) p-cresol at 110
      degrees C for 48 h) accompanied with the hydrolysis of elastin. A bis-p-cresol
      derivative of allysine was isolated from bovine ligamentum nuchae elastin
      hydrolysates, and was characterized by UV, FAB-MS and NMR. This derivative was
      identified as 2-amino-6,6-bis(2-hydroxy-5-methylphenyl)hexanoic acid. A rapid,
      sensitive reverse-phase high-performance liquid chromatographic method with UV
      detection was developed for the quantitative determination of allysine as its bis
      p-cresol derivative. The lower limit of detection of the bis-p-cresol derivative
      was 58 pmol in the standard sample with a 20-microl injection at a signal-to
      noise ratio of 3. This method was applied to the determination of allysine in
      bovine ligamentum nuchae, aorta, lung, and rat aorta elastin. The allysine
      content in rat aorta elastin dramatically increased from 1 week to 2 weeks of
      age.

PMID- 11332454
TI  - Renal amino acid transport in immature and adult rats during chromate and
      cisplatinum-induced nephrotoxicity.
AB  - The effects of sodium dichromate (chromate; 1 mg/100 g b. wt. s.c.) and
      cisdiamminedichloroplatinum(II) (CP; 0.6 mg/100 g b. wt. i. p.) on renal amino
      acid excretion and plasma amino acid composition were investigated in 10- and 55
      day-old anaesthetised rats. On the basis of diuresis experiments on conscious
      rats the mentioned doses and times (1st day after chromate in both age groups and
      in 10-day-old rats after CP and 3rd day after CP in adult rats) were found out to
      be optimal for the characterisation of amino acid transport after heavy metal
      poisoning. Interestingly, in conscious 10-day-old rats chromate nephrotoxicity is
      not detectable after 1 mg/100 g b. wt. whereas all of the other experimental
      groups showed nephrotoxic effects of chromate and CP in conscious rats. Urine
      volumes are lower, but not significantly, in anaesthetised immature rats,
      independently of the administered nephrotoxin. But GFR is significantly lower in
      10-day-old rats, both in controls and after CP, whereas after chromate GFR is
      significantly reduced only in adult rats and age differences disappeared. In
      principle the renal fractional excretion (FE) of amino acids was distinctly
      higher in immature rats as a sign of lower amino acid reabsorption capacity.
      Nevertheless, the amino acid plasma concentrations were relatively high in
      immature rats. However, both chromate and CP did not distinctly influence amino
      acid plasma concentrations. But in both age groups the administration of chromate
      and CP significantly decreased amino acid reabsorption capacity (increase in FE)
      as a sign of nephrotoxicity, most pronounced in adult rats after CP. The
      investigation of renal amino acid handling confirms (1) that both CP and chromate
      are nephrotoxins, (2) that CP was more nephrotoxic in 55-day-old animals compared
      to immature rats as could be demonstrated before using other parameters for
      nephrotoxicity testing and showed (3) that determination of renal amino acid
      handling is a highly sensitive marker for nephrotoxicity testing, especially in
      immature rats.

PMID- 11332455
TI  - The role of eukaryotic initiation factor 5A in the control of cell proliferation
      and apoptosis.
AB  - In the past years, the attention of scientists has mainly focused on the study of
      the genetic information and alterations that regulate eukaryotic cell
      proliferation and that lead to neoplastic transformation. An increasing series of
      data are emerging about the involvement of the initiation phase of translational
      processes in the control of cell proliferation. In this paper we review the novel
      insights on the biochemical and molecular events leading to the initiation and
      its involvement in cell proliferation and tumourigenesis. We describe the
      structure, regulation and proposed functions of the eukaryotic initiation factor
      5A (eIF-5A) focusing the attention on its involvement in the regulation of
      apoptosis and cell proliferation. Moreover, we describe the modulation of its
      activity (through the reduction of hypusine synthesis) in apoptosis induced
      either by tissue transglutaminase or interferon a. Finally, we propose eIF-5A as
      an additional target of anti-cancer strategies.

PMID- 11332456
TI  - Magnetoencephalography and magnetic source imaging in children.
AB  - Magnetoencephalography is a technique that detects the magnetic fields associated
      with the intracellular current flow within neurons, unlike
      electroencephalography, which measures extracellular volume currents.
      Superconducting quantum interference devices are used to amplify these very small
      magnetic field signals. Magnetic source imaging is the combination of functional
      data derived from magnetoencephalographic recordings coregistered with structural
      magnetic resonance imaging (MRI). The utility of magnetic source imaging lies in
      the combination of the submillisecond temporal resolution of
      magnetoencephalography with the precise anatomic images provided by magnetic
      resonance imaging. As such, magnetic source imaging is a useful tool for
      noninvasive localization of the epileptogenic zone in children who are candidates
      for epilepsy surgery. Similarly, using magnetoencephalographic recordings with
      evoked and event-related potentials, magnetic source imaging holds great promise
      as a noninvasive method for precise localization of somatosensory, motor,
      language, visual, and auditory cortex. Finally, magnetic source imaging is
      proving a valuable research tool in the investigation of epilepsy, head trauma,
      brain plasticity, and disorders of language, memory, cognition, and executive
      function in children.

PMID- 11332457
TI  - Vigilance scoring in children with acquired brain injury: Vienna Vigilance Score
      in comparison with usual coma scales.
AB  - An instrument in neurologic rehabilitation for the assessment of a person's
      clarity of consciousness must fulfill the need to provide the rehabilitation team
      with some information regarding the structuring of the rehabilitation process.
      The Vienna Vigilance Score is oriented toward cooperation within the
      rehabilitation team with the specific advantage of focus on the subject status of
      the patient on the basis of the dialogue. It does not use painful stimuli and is
      oriented toward the next developmental step of the rehabilitation process. The
      first extensive application of the Vienna Vigilance Score was carried out in a 3
      year study of 38 children and adolescents. We report the comparison with other
      coma scales (Glasgow Coma Scale, Children's Coma Score, and Modified Glasgow Coma
      Scale) on 24 children and adolescents (1.4-16.8 years of age). The results showed
      satisfying statistical parameters: measuring range comparable with other scales;
      a Kendall tau correlation of .59 on both the Modified Glasgow Coma Scale and the
      Children's Coma Scale and of .66 on the Glasgow Coma Scale; a Spearman's rank
      order correlation of .70 to both the Modified Glasgow Coma Scale and the
      Children's Coma Scale and of .78 on the Glasgow Coma Scale. By accepting the
      Glasgow Coma Scale as a gold standard for classification of the level of coma, we
      can confirm satisfactory measuring qualities for the Vienna Vigilance Score.

PMID- 11332458
TI  - Brain plasticity for sensory and linguistic functions: a functional imaging study
      using magnetoencephalography with children and young adults.
AB  - In this report, the newest of the functional imaging methods,
      magnetoencephalography, is described, and its use in addressing the issue of
      brain reorganization for basic sensory and linguistic functions is documented in
      a series of 10 children and young adults. These patients presented with a wide
      variety of conditions, ranging from tumors and focal epilepsy to reading
      disability. In all cases, clear evidence of reorganization of the brain
      mechanisms of either somatosensory or linguistic functions or both was obtained,
      demonstrating the utility of magnetoencephalography in studying, completely
      noninvasively, the issue of plasticity in the developing brain.

PMID- 11332459
TI  - Functional magnetic resonance imaging in children with Asperger's syndrome.
AB  - Asperger's syndrome is a pervasive developmental disorder of unknown etiology. We
      evaluated children with this syndrome (n = 9) and control (n = 8) children by
      functional magnetic resonance imaging (MRI) during a task involving social
      judgment. All control and 5 of 9 subjects with Asperger's syndrome showed signal
      intensity changes in frontal regions. Four patients with Asperger's syndrome,
      including one case with right frontal dysplasia, had no signal intensity change
      during the task. In this first functional MRI study of childhood Asperger's
      syndrome, frontal activation patterns demonstrated some differences between
      patients and normal subjects. Further studies using other functions frequently
      impaired in Asperger's syndrome are warranted.

PMID- 11332460
TI  - Comparative utility of technetium-99m hexamethylpropylenamine oxime single photon
      emission computed tomography (SPECT) with anatomic neuroimaging and
      electroencephalography (EEG) in childhood intractable epilepsy.
AB  - Intractable epilepsies pose a therapeutic challenge. Precise localization of the
      epileptic focus is imperative before planning surgical intervention. Functional
      imaging is an important component of presurgical work-up. Positron emission
      tomography is unavailable in developing countries; hence, the need to evaluate
      the available imaging modality, single photon emission computed tomography
      (SPECT), was felt. We investigated 61 children with intractable epilepsy,
      identified by predefined criteria, by performing electroencephalography (EEG),
      magnetic resonance imaging (MRI), computed tomography (CT), and ictal and
      interictal SPECT. The localizing value of ictal and interictal SPECT imaging for
      epileptic foci was correlated with clinical, electrophysiologic, and anatomic
      neuroimaging data. An ictal SPECT was obtained in 9, and interictal SPECT was
      performed in all (61). Ictal SPECT was localizing in 8 of 9 (88.8%). Interictal
      SPECT was localizing in a significantly higher proportion of patients (47.54%)
      than either the scalp EEG (16.39%) (P = .0003) or CT scan (21.56%) (P = .0046).
      Our data demonstrated that interictal and ictal SPECT identified more focal
      changes in children with intractable epilepsy than interictal EEG, CT, and
      probably MRI. The definitive proof of the SPECT-based findings being
      epileptogenic foci awaits correlation with intraoperative monitoring and
      postoperative follow-up.

PMID- 11332461
TI  - Molybdenum cofactor deficiency: report of three cases presenting as hypoxic
      ischemic encephalopathy.
AB  - We report three infants with the diagnosis of molybdenum cofactor deficiency. The
      key findings leading to diagnosis were neonatal seizures unresponsive to
      treatment, craniofacial dysmorphic features, hyperexcitability, low blood uric
      acid levels, and neuroimaging findings. The parents were consanguineous in two of
      these patients. The diagnosis was established by the presence of low blood uric
      acid levels, positive urine sulfite reaction, quantitative aminoacid analysis,
      and high-voltage electrophoresis of the urine sample showing a typical increase
      of S-sulfo-L-cysteine. Skin fibroblast cultures confirmed the diagnosis. Magnetic
      resonance imaging findings were suggestive of encephalomalacia with cystic
      changes due to hypoxic-ischemic encephalopathy. We conclude that molybdenum
      cofactor deficiency must be included in the differential diagnosis of patients
      presenting with intractable seizures in the newborn period who have computed
      tomography and magnetic resonance imaging findings reminiscent of those of
      hypoxic-ischemic encephalopathy, and the urine sulfite dipstick test can be a
      part of the evaluation of these infants in neonatal intensive care units.

PMID- 11332462
TI  - Molecular ontogeny of major neurotransmitter receptor systems in the mammalian
      central nervous system: norepinephrine, dopamine, serotonin, acetylcholine, and
      glycine.
AB  - Neurotransmitter receptors are critical elements in intercellular signaling
      within the central nervous system and are divided into two major types based on
      their molecular structure and biophysical properties. The first are ionotropic
      receptors--ligand-gated ion channels that directly affect the membrane potential
      via passage of permeant ions (such as sodium and calcium) and mediate fast
      synaptic transmission. The second type are slower metabotropic receptors that are
      also ligand gated but depend on an interaction with guanine nucleotide-binding
      proteins and mediate signal transduction by activating second-messenger systems
      within the cell. In the past two decades, a wealth of information has emerged
      regarding the molecular biology and pharmacology of classic neurotransmitter
      receptors (including adrenergic, dopaminergic, serotonergic, cholinergic,
      glycine, gamma-aminobutyric acid [GABA(A)], and glutamate receptors). Further,
      the distribution of subunits comprising these receptors has been extensively
      studied. This review focuses on the molecular ontogeny of several of the major
      neurotransmitter receptor systems in the mammalian central nervous system,
      highlighting the role that some of these may play during brain development and in
      certain pathologic states.

PMID- 11332463
TI  - Thrombolytic therapy in an adolescent ischemic stroke.
AB  - We report the case of a 16-year-old Caucasian girl who developed acute onset of
      left hemiplegia, left hemisensory deficit, and dysarthria. After a negative
      computed tomographic scan of the brain, the patient was given intravenous
      recombinant tissue plasminogen activator according to established adult
      guidelines. The patient experienced a marked improvement within 24 hours. Stroke
      etiology was determined to be a paradoxical embolus via a patent foramen ovale
      associated with pelvic vein thrombosis. This case illustrates the importance of
      early recognition of stroke and the utility of thrombolytics in treating ischemic
      infarcts in the adolescent population.

PMID- 11332464
TI  - Cognition, attention, and behavior in Prader-Willi syndrome.
AB  - We studied the academic, cognitive, and behavior profile of 18 patients with
      Prader-Willi syndrome. All had severe learning disabilities in arithmetic and
      writing, and the majority were also dyslexic. Their average Full-Scale IQ was
      73.7 +/- 8.9, which was 1 SD below normal range, whereas their performance on
      executive, memory, and visuospatial tasks ranged from 2.1 to 7.0 SD below the
      expected means. Behavioral problems were measured using the Child Behavior
      Checklist, on which the majority scored in the pathologic range for social and
      attention problems, delinquent and aggressive behavior, somatic complaints, and
      thought problems. Genotypes of the children did not predict cognitive or
      behavioral profile, nor could behavior be associated with parameters of weight or
      IQ. In summary, we found that patients with Prader-Willi syndrome have profound
      learning disabilities and cognitive deficits, greater than expected for their IQ.
      Behavioral problems, including attention-deficit hyperactivity disorder (ADHD),
      are also prevalent and impede the overall management of this group of patients.
      The genotypes were not helpful in predicting cognitive or behavioral patterns.

PMID- 11332465
TI  - Molecular genetic study of a childhood form of spinal muscular atrophy.
AB  - Molecular genetic studies were performed in 28 cases of childhood-onset spinal
      muscular atrophy (24 unrelated families). This consisted of type 1 (severe) (n =
      5), type 2 (intermediate form) (n = 8), and type 3 (mild) (n = 15). Deletion of
      exons 7 and 8 of the SMNt gene was found in 100%, 100%, and 93%, respectively, in
      type 1, 2, and 3 spinal muscular atrophy. Deletion of exons 5 and 6 of the NAIP
      gene was found in 3 of 5 (60%) of type 1 and none of the type 2 and 3 cases. None
      of the 32 asymptomatic relatives had homozygous deletions in the SMNt and NAIP
      genes. Thus, the role of the NAIP gene needs to be specifically defined in spinal
      muscular atrophy. In a suspected case of spinal muscular atrophy, deletion of the
      SMNt gene is a useful laboratory marker for confirmation of the diagnosis.

PMID- 11332466
TI  - Plasminogen activator inhibitor-1 4G/5G polymorphism in Turkish children with
      cerebral infarct and effect on factor V 1691 A mutation.
AB  - The thrombotic risk of carrying plasminogen activator inhibitor-1-675 4G allele
      was found to be controversial in previous studies. The aim of this study was to
      evaluate the possible effect of plasminogen activator inhibitor-1 4G/5G
      polymorphism in the pathogenesis of childhood stroke. The case-control study
      included 43 patients with cerebral infarct who were below the age of 18 years
      (range, 10 months to 18 years) and 113 healthy unrelated individuals without
      family histories of thrombosis. Plasminogen activator inhibitor-1 4G/5G
      polymorphism was analyzed according to a previously described method. There was
      no statistically significant difference in patient and control groups for the
      distribution of plasminogen activator inhibitor-1 4G/5G polymorphism (P = .75)
      (allele frequency 4G controls: 0.50; patients: 0.53). However, there was a
      significant difference for the factor V (FV) 1691 A mutation for both groups (P =
      .0007).

PMID- 11332467
TI  - Facial and skeletal malformations, mental retardation, aganglionosis, and
      neurogenic muscle weakness: a variant of Niikawa-Kuroki syndrome or a new
      syndrome?
AB  - We report a 10-year-old boy with multiple congenital anomalies/mental retardation
      syndrome, who also presented with aganglionosis and neurogenic muscle weakness.
      Some phenotypic manifestations of our patient overlap with those observed in the
      Niikawa-Kuroki syndrome; however, the hypothesis of a new distinct entity, with
      simultaneous involvement of the central and peripheral nervous system, is
      considered.

PMID- 11332468
TI  - Cardiovascular evaluation of syncope.

PMID- 11332469
TI  - Parasagittal injury in infants with hypoxic-ischemic encephalopathy.

PMID- 11332470
TI  - Genetic stability of the VP2 hypervariable region of four infectious bursal
      disease virus isolates after serial passage in specific-pathogen-free chicken
      embryos.
AB  - Infectious bursal disease virus strains U2, 586, L1, and Q2 were isolated from
      pooled bursal samples collected from commercially reared broilers. These viruses
      were propagated in specific-pathogen-free (SPF) embryonated chicken eggs for 24
      or 25 passages. Nucleotide sequences of a 743-bp reverse transcription
      (RT)/polymerase chain reaction (PCR) product containing the VP2 hypervariable
      region were compared before and after passage of the viruses in embryonated
      chicken eggs. To determine the genetic stability of the viruses, each isolate was
      compared with its egg-passed ancestor; virus isolates were not compared with each
      other. When the restriction enzymes BstNI and MboI were used, no differences were
      observed in the restriction fragment length polymorphism profiles of the RT/ PCR
      products after embryo passage. After embryo passage, six nucleotide changes were
      identified in the viruses. Among the four viruses examined, these nucleotide
      changes resulted in a total of five amino acid changes. The amino acid changes
      were S-222-L in virus 586, K-249-N in viruses U2, L1, and Q2, and G-281-V in
      virus Q2. Three of the five amino acid changes occurred at residue 249. The
      convergent nature of this residue shift in three of four of the chick embryo
      passed viruses suggests the occurrence of a functional, as opposed to random,
      mutation. The original isolates caused typical signs of infectious bursal disease
      in 3-wk-old SPF chicks. Their embryo-passed ancestors also produced typical signs
      of infectious bursal disease in 3-wk-old SPF chicks, suggesting the amino acid
      mutations observed did not affect virulence of the viruses.

PMID- 11332471
TI  - In vivo events of retroviral long terminal repeat integration into Marek's
      disease virus in commercial poultry: detection of chimeric molecules as a marker.
AB  - The present study demonstrated, for the first time, that not only in vitro, but
      also in vivo, coinfections with Marek's disease virus (MDV) and each of the three
      avian retroviruses (reticuloendotheliosis virus [REV], avian lymphoid leukosis
      virus [ALV], and ALV-J) lead to retroviral long terminal repeat (LTR) integration
      into MDV. A total of 306 chicken and 59 turkey commercial flocks, submitted for
      differential avian oncogenic virus diagnosis, served to evaluate the flock mixed
      virus infection rate, the rate of birds with a multiple virus infection, and the
      issue of retroviral LTR integration into MDV in vivo. About a quarter of the
      tumor-bearing commercial flocks carried a mixed MDV and retrovirus infection. A
      total of 2926 DNA samples were analyzed, including 2428 chicken and 498 turkey
      DNA samples. Of these, 991 DNAs originated from flocks with a multiple virus
      infection. In 103 DNA preparations from that group (103/991, 10.4%), including 38
      and 56 from chicken blood and tumor tissues, respectively, and nine samples from
      turkey blood, multiple virus sequences were detected by polymerase chain reaction
      (PCR). Fifty-six of the 103 samples were further analyzed by the previously
      developed hot spot-combined (HS-cPCR assay, of which 48% (27/56) contained
      chimeric MDV and retroviral LTR molecules. When extrapolated to the total samples
      derived from the flocks with multiple virus infection, that rate implies that
      about 5% of the DNA samples would carry MDV-retrovirus integration events.
      Several birds held a variety of chimeric molecules, indicating that several
      recombination events occurred simultaneously. The validation of the MDV and
      retroviral LTR chimeric constitution of these molecules was derived by the MDV
      and retroviral heterologous primers used for their creation by the HS-cPCR assay,
      Southern blotting and their detection by retroviral LTR probes, and LTR
      amplification from the gel-purified chimeric molecules. From several molecules,
      the LTR was sequenced, and a 161-bp retroviral LTR sequence was demonstrated. Our
      biochemical data imply that a recent integration occurred in the birds. The
      viability of recombinant viruses represented by the chimeric molecules will be
      further approached.

PMID- 11332472
TI  - Antibody responses of hens fed vitamin E and passively acquired antibodies of
      their chicks.
AB  - Antibody responses of hens and their progeny were studied in commercial broiler
      nuclear lines. Starting at 168 days of age, individually housed pullets from
      lines A and B were fed a 16% crude protein and 2752 kcal metabolizable energy/kg
      mash diet supplemented with either 10 or 300 IU/kg of vitamin E fed as dl-alpha
      tocopherol acetate. Fifty-eight days later (226 days of age), 12 hens per line
      vitamin E subclass were inoculated i.v. with 0.1 ml of a 2.5% suspension of sheep
      red blood cells (SRBC). Plasma antibody titers were measured 6, 20, 40, 54, 70,
      and 88 days after inoculation. Hens from both lines were artificially mated to
      males from line C, and progeny from eggs collected 9-15, 25-30, and 65-70 days
      after inoculation were tested for antibodies to SRBC. Hens were reinoculated i.v.
      with 0.1 ml of 0.25% SRBC 88 days after the first inoculation, and their antibody
      levels were measured 3, 6, and 20 days later. Eggs laid 10-13 days after
      reinoculation were incubated, and antibody titers of chicks were measured at
      hatch. Antibody response of hens to an initial inoculation of SRBC was line-diet
      time after inoculation specific. In line A, titers were greater for hens fed the
      lower than the higher vitamin E diet, whereas diet had no effect on the antibody
      levels in line B. Line effects (A > B) were observed on days 6 and 20 after
      inoculation but not thereafter. After the second inoculation, dietary vitamin E
      level had no effect on antibody levels of hens within lines, whereas a between
      line difference (A > B) was observed for the lower but not the higher level of
      dietary vitamin E. Although there was no difference between diets for antibody
      transferred to progeny by line B, there was a difference (lower > higher) for
      line A. After reinoculation of their dams, antibody titers of chicks from line A,
      but not line B, reached levels similar to those after the first inoculation.
      Antibody levels were higher for chicks at hatch than in 16-day embryos or 10 days
      posthatch. The results of this research suggest genetic variation in response to
      immune stimulation by dietary vitamin E.

PMID- 11332473
TI  - Fecal shedding and antimicrobial susceptibility of selected bacterial pathogens
      and a survey of intestinal parasites in free-living waterfowl.
AB  - Free-living waterfowl residing in metropolitan parks in central Ohio were
      surveyed for the fecal shedding and antimicrobial susceptibility patterns of
      Campylobacter jejuni, Escherichia coli, Salmonella spp., and Pasteurella
      multocida. In addition, a survey for intestinal parasites was also conducted in
      these same waterfowl to determine parasite burdens in free-living waterfowl.
      Prevalences of 67%, 50%, and 0.2% of E. coli, C. jejuni, and Salmonella spp.,
      respectively, were observed for all waterfowl species. Pasteurella multocida was
      not isolated from the sampled population. Salmonella java was isolated from one
      mallard duck. Statistically, there was a significantly higher E. coli isolation
      rate for mallard ducks than for Canada geese, but no difference was observed for
      C. jejuni isolation rates between waterfowl species. Antimicrobial susceptibility
      testing was conducted via the disk diffusion method and multidrug resistance was
      exhibited for penicillin G, lincomycin, vancomycin, erythromycin, and bacitracin.
      In addition, the prevalence of endoparasites in these sampled waterfowl ranged
      from 5% to 66%. Protozoan oocysts were most prevalent followed by nematode ova.
      No trematode or cestode ovum was recovered from this sampled population.

PMID- 11332474
TI  - Baculovirus expression of turkey coronavirus nucleocapsid protein.
AB  - The nucleocapsid (N) gene of turkey coronavirus (TCV) was amplified by reverse
      transcriptase-polymerase chain reaction, cloned, and expressed in the baculovirus
      expression system. A recombinant baculovirus containing the TCV N gene (rBTCV/N)
      was identified by polymerase chain reaction and expression of TCV N protein as
      determined by western immunoblot analysis. Two TCV-specific proteins, 52 and 43
      kDa, were expressed by rBTCV/N; one of these proteins, p52, was comparable in
      size to native TCV N protein. Baculovirus-expressed N proteins were used as
      antigen in an indirect enzyme-linked immunosorbent assay (ELISA) for detection of
      TCV-specific antibodies. The ELISA detected antibodies specific for TCV and
      infectious bronchitis virus, a closely related avian coronavirus, but did not
      detect antibodies specific for other avian viruses (avian influenza, avian
      reovirus, avian paramyxovirus 3, avian adenovirus 1, or Newcastle disease virus).
      These findings indicate that baculovirus-expressed TCV N protein is a suitable
      source of antigen for ELISA-based detection of TCV-specific antibodies in
      turkeys.

PMID- 11332475
TI  - Safety and efficacy of in ovo administration of infectious bursal disease viral
      vaccines.
AB  - In ovo vaccination against Marek's disease virus and infectious bursal disease
      virus (IBDV) in commercial broilers in the United States is common. Little
      information exists as to the safety and efficacy of intermediate IBDV vaccines
      given in ovo. Experiments were initiated to determine the safety and efficacy of
      three commercially available live intermediate IBDV vaccines by in ovo route.
      Commonly used vaccines were given at 18 days of embryonation to specific-pathogen
      free (SPF) broiler embryos (first and second study) or to commercial broiler
      embryos (third study) that had maternal antibody against IBDV. When any of the
      antigenic standard vaccines was given at full dose to SPF embryos, embryonic and
      3-wk posthatch mortality increased. Vaccines also caused significant microscopic
      lesions in the bursa of Fabricius at 1 and 3 wk posthatch. In contrast, there was
      no adverse effect on embryonic or posthatch mortality when vaccines were given at
      half dose to SPF or commercial broiler embryos. However, significant microscopic
      lesions were evident at 1 and 3 wk posthatch in the bursae of SPF embryos given
      the vaccines at half dose. When vaccines were given at half dose to commercial
      broiler embryos, lesions were evident at 1 but not 3 wk of age. In the third
      study, in ovo vaccinated chickens were challenged with either a virulent standard
      (APHIS) or antigenic variant (variant E) IBDV virus at 3 wk of age. All vaccines
      produced at least 87% protection against the standard and 60% protection against
      the variant challenge IBDV, as measured by bursal weight to body weight ratios.
      This study was the first to examine the safety and efficacy of the three commonly
      used intermediate IBDV vaccines given in ovo in protection against standard and
      antigenic variant IBDV challenge viruses.

PMID- 11332476
TI  - Reduced incidence of Clostridium perfringens-associated lesions and improved
      performance in broiler chickens treated with normal intestinal bacteria from
      adult fowl.
AB  - The dosing of young chicks with cultures of normal gut flora has been termed
      "competitive exclusion" (CE). This study was undertaken to examine, under field
      conditions, the effect of CE treatment on counts of intestinal Clostridium
      perfringens (CP) and on the occurrence of CP-associated disease in broiler
      chickens. A farm having recurrent CP-associated health problems was selected as
      study site. The study comprised four broiler houses, with one treated and one
      untreated flock per house. Treated birds were sprayed with the CE product
      Broilact upon arrival at the farm. All flocks were offered feed containing the
      ionophorous anticoccidial agent narasin. The feed did not contain growth
      promoters. Treatment was associated with positive but statistically
      nonsignificant effects on gut health. Delayed intestinal proliferation of CP and
      delayed appearance of CP-associated gut lesions were found in CE-treated flocks.
      This delay was associated with improved production performance at slaughter.

PMID- 11332477
TI  - Experimental bovine coronavirus in turkey poults and young chickens.
AB  - The DB2 calf strain of bovine coronavirus (BCV) was used to inoculate 1-day-old
      specific-pathogen-free (SPF) turkey poults in three trials. In all trials, the
      birds developed clinical signs of enteritis at 48-72 hr postinoculation. Birds
      euthanatized at 3, 5, and 7 days postinoculation (DPI) had flaccid, pale
      intestines with watery contents, and the ceca were markedly enlarged with frothy
      contents. Coronavirus particles were detected by immune electron microscopy with
      BCV antibodies from the intestinal contents of birds killed at 3, 5, 7, and 12
      DPI. Body weights of inoculated poults killed at 3, 5, and 7 DPI were
      significantly reduced as compared with controls. Hemagglutinating antibodies were
      detected in sera of convalescent birds at 12 DPI. However, experimental
      inoculation of 1-day-old SPF chicks in two trials with the same virus resulted in
      no clinical signs or macroscopic or microscopic lesions. No coronaviruses were
      detected from intestinal contents, and there were no significant differences in
      body weights of inoculated and noninoculated control chicks.

PMID- 11332478
TI  - Identification and analysis of the Georgia 98 serotype, a new serotype of
      infectious bronchitis virus.
AB  - Twenty-five field infectious bronchitis viruses (IBVs) similar to, but
      genetically distinct from, the DE072 serotype were isolated from several states
      in the United States from 1990 through 1999 and were examined molecularly and
      antigenically. A 421-bp sequence in the hypervariable region of the S1 gene was
      examined, and phylogenetic analysis on that region indicated that these viruses
      are closely related but fall into unique groups. Cross-virus neutralization
      testing and entire S1 sequence analysis on selected isolates further confirmed
      that fact, and we divided the viruses into the DE072 serotype and two other
      unique groups. In a vaccine protection trial, the commercially available DE072
      vaccine showed less than 50% protection against viruses in one of the groups. The
      majority of the recent isolates belong to that group and share very low antigenic
      relatedness to the DE072 strain as well as other serotypes of IBV. Consequently,
      we designated this group as a new serotype, Georgia 98. We developed a
      restriction fragment length polymorphism analysis that can differentiate this new
      serotype from all other serotypes of IBV.

PMID- 11332479
TI  - Genetic variability of avian Escherichia coli strains evaluated by
      enterobacterial repetitive intergenic consensus and repetitive extragenic
      palindromic polymerase chain reaction.
AB  - In this study, we tested the capability of enterobacterial repetitive intergenic
      consensus (ERIC) and repetitive extragenic palindromic (REP) polymerase chain
      reaction (PCR) to detect genetic diversity among Escherichia coli strains
      isolated from chickens bearing clinical signs of colibacillosis and compared the
      genotypes so obtained with the O:H serotypes and virulence of those strains. The
      DNAs from 50 avian E. coli strains and from E. coli ATCC 25922 were used to
      amplify ERIC and REP sequences. DNA from avian strains produced from 8 to 17
      bands by ERIC-PCR and from 6 to 20 bands by REP-PCR; E. coli ATCC produced 11
      bands by both methods. ERIC and REP-PCR showed good discriminating power, and the
      dendograms based on the different patterns revealed extensive genetic diversity
      among the avian strains. Those strains were allocated into four major clonal
      clusters, each one with 60% of similarity by ERIC and REP-PCR, and those clusters
      corresponded to strains with different degrees of pathogenicity. However, 56% of
      the pathogenic strains (28/50) belonged to two out of three major clonal
      clusters, and 86% of the nonpathogenic strains tended to group in one cluster and
      one subgroup. The 32 serotypes detected were distributed in all clusters, and
      within a serogroup, different DNA fingerprints were observed; however, strains
      with same serotypes tended to form clusters with similarity coefficients greater
      than 80%. These results suggest that no specific serotype and genotype is
      responsible for colibacillosis and that REP and ERIC-PCR are reproducible
      techniques that can improve the studies needed to clarify the pathways to the
      pathogenesis of colibacillosis.

PMID- 11332480
TI  - Prevalence and characteristics of Pasteurella multocida in commercial turkeys.
AB  - The oropharyngeal regions of 680 meat turkeys and 55 breeder turkeys from nine
      outbreak farms, three history-outbreak farms, and 19 nonoutbreak farms in Ohio,
      Indiana, and Pennsylvania were cultured to determine the prevalence of
      Pasteurella multocida in turkeys. Pasteurella multocida was recovered from 32 out
      of 105 turkeys belonging to outbreak farms. Pasteurella multocida was not
      recovered from either history-outbreak or nonoutbreak farms. Characterization via
      capsular and somatic serotyping, biotyping, restriction endonuclease analysis,
      and antimicrobial susceptibility testing was performed on all recovered P.
      multocida isolates. Pasteurella multocida serotype A:1 and somatic serotype 1
      with an un-typable capsular serogroup (UT:1) were the most common serogroups
      found. All isolates belonged to biotype P. multocida ssp. multocida. EcoRI,
      HpaII, and HindIII restriction enzyme digestions identified three, five, and five
      restriction fragment length polymorphism profiles, respectively. A majority of
      the isolates were susceptible to amikacin, ampicillin, ceftiofur, cephalothin,
      enrofloxacin, florfenicol, gentamicin, neomycin, novobiocin, oxacillin with 2%
      NaCl, sarafloxacin, tilmicosin, and trimethoprim with sulphadiazine and resistant
      to clindamicin, penicillin, tiamulin, and tylosin.

PMID- 11332481
TI  - Experimental infection of specific-pathogen-free chickens with serotype-1 fowl
      adenovirus isolated from a broiler chicken with gizzard erosions.
AB  - Gizzard lesions were formed in specific-pathogen-free (SPF) white leghorn
      chickens inoculated with fowl adenovirus (FAV). The virus, serotype 1 FAV 99ZH
      strain (FAV-99ZH), was originally isolated from the gizzard mucosa of commercial
      broiler chickens exhibiting gizzard erosion with intranuclear inclusion bodies.
      Five-day-old and 53-day-old SPF white leghorn chickens were inoculated with FAV
      99ZH by both oral and ocular routes and then examined at necropsy on days 3, 5,
      7, 10, 14, and 21 postinoculation (PI). There were no clinical signs in any of
      the chickens after the inoculation. Focal gizzard lesions occurred
      macroscopically, however, in inoculated chickens at several experimental periods.
      FAV was recovered from tissue samples of the proventriculus, gizzard, pancreas,
      and rectum by day 10 or 7 PI but was not recovered from liver samples of any of
      the chickens. These results indicate that FAV isolated from gizzard erosion is
      able to reproduce gizzard lesions as necrosis and erosion in SPF white leghorn
      chickens and that it may have a greater degree of tissue tropism in gizzards and
      other digestive organs than in the liver.

PMID- 11332482
TI  - Cellulitis in broiler chickens: a one-year retrospective study in four Quebec
      abattoirs.
AB  - A 1-yr retrospective study was undertaken to verify whether the prevalence of
      cellulitis in broiler chicken flocks was associated 1) with sex and average body
      weight controlling for the time of year and 2) with some other condemnation
      causes such as air-sacculitis, ascites, cyanosis, emaciation, valgus varus
      deformity, peritonitis, and total condemnation rate controlling for sex, average
      body weight, and time of year. Data were collected from four Quebec abattoirs
      between October 1992 and September 1993. Data from 2452 unisex male and female
      broiler flocks were compiled and analyzed with univariate and multivariate
      models. The prevalence of cellulitis among flocks was 42.2 per 10,000 birds
      slaughtered. Cellulitis was associated with sex and increased with time of year
      (P < 0.0001). The prevalence was higher in male (mean +/- SD, 50.7+/-24.3;
      median, 31.8) than in female flocks (mean +/- SD, 34.2+/-15.6; median, 20.0) but
      showed no relationship with average body weight. Associations between
      condemnation causes and cellulitis were relatively weak; increases in the
      prevalence of cellulitis correlated with increases in total condemnation rate (r2
      = 0.19), ascites (r2 = 0.09), airsacculitis (r2 = 0.0), cyanosis (r2 = 0.04),
      peritonitis (r2 = 0.03), emaciation (r2 = 0.02), and valgus varus deformity (r2 =
      0.02). These results suggest that flock sex is a potential correlate of
      cellulitis prevalence in broiler chickens. Associations between the prevalence of
      cellulitis and other diseases observed at the abattoir were not very strong.
      However, it appears here that general disease status of Quebec broiler flocks is
      a better indicator of cellulitis occurrence than the main diseases considered
      individually.

PMID- 11332483
TI  - Comparison of Salmonella isolation rates in different types of egg-layer hen
      houses in Chiba, Japan.
AB  - This study investigated the differences in Salmonella isolation rates in
      environmental samples taken from several types of hen houses in Chiba, Japan. In
      addition, for the detailed epidemiologic survey, environmental samples, hens, and
      rodents were collected from Salmonella-contaminated windowless houses on three
      farms. As a result, Salmonella was isolated from four (80%) of five farms with
      windowless hen houses; Salmonella enteritidis was isolated from a single
      windowless house. In contrast, only one serotype of Salmonella was isolated from
      1 (6.7%) of 15 farms with open hen houses. In the S. enteritidis-contaminated
      windowless hen house, the isolation rates of S. enteritidis as compared with the
      other serotypes were 90.9% of environments, 94.1% of hens, and 86.4% of roof rats
      (Rattus rattus) that resided in the environments. In reference to the phage type
      (PT) of these isolates, PT1 was detected in environments and roof rats, and PT9
      was detected in both these samples and in hens. Thus, the Salmonella isolation
      rate in hen houses seems to be associated with whether the premises are
      windowless or open. Moreover, roof rats appear to be the most important vectors
      in the spread of S. enteritidis in the windowless hen house because the S.
      enteritidis PTs coincide with each other.

PMID- 11332484
TI  - Molecular epidemiology of infectious bronchitis virus isolates from China and
      Southeast Asia.
AB  - In order to trace the origin and evolution of avian infectious bronchitis virus
      (IBV) isolates in China and Southeast Asia, genomic sequencing was used for
      molecular characterization of 24 IBV isolates and two reference strains in
      comparison with the published sequences. The 5' region of the S1 genes,
      containing hypervariable regions I and II, and 3' region of the nucleocapsid
      genes, containing cytotoxic T lymphocyte epitopes, were used to construct
      phylogenetic trees for analysis. The results showed that the 24 isolates could be
      divided into three distinct groups, that is, American, Asian, and European. Some
      isolates formed a distinct Asian phylogenetic group, suggesting that IBV has
      existed for some time in Asia. Our results also showed that in vivo recombination
      of IBV may have occurred at a rather high frequency, contributing to the
      diversity of these IBV isolates. Importantly, recombination events have probably
      occurred between vaccine strains and field strains in the natural condition.

PMID- 11332485
TI  - Efficacy of narasin in the prevention of necrotic enteritis in broiler chickens.
AB  - The efficacy of narasin in the control of necrotic enteritis (NE) was
      investigated in a floor pen study of 2000 broiler chickens using a Clostridium
      perfringens feed inoculum challenge model. Treatments were 1) nonmedicated,
      nonchallenged; 2) nonmedicated, challenged; 3) narasin, nonchallenged; 4)
      narasin, challenged. Narasin was administered at 70 ppm in the feed from day 0 to
      trial termination on day 41. Challenge inoculum contained approximately 1 x 10(8)
      colony-forming units CP/ml and was administered from day 14 to day 16. In the
      unmedicated groups, challenged birds had significantly (P < 0.05) lower mean body
      weight and reduced feed efficiency at day 21 and significantly (P < 0.01) higher
      cumulative NE mortality at day 41 compared with unchallenged. Similarly, among
      unmedicated birds, those challenged had a significantly (P < 0.01) higher mean NE
      score on day 17 and significantly (P < 0.05) higher mean huddling scores on days
      15-17 than unchallenged. Among challenged birds, those fed narasin had
      significantly (P < 0.05) higher mean body weight and improved feed efficiency at
      days 21 and 41 and significantly (P < 0.01) lower cumulative NE mortality at day
      41 than unmedicated. Similarly, among challenged birds, those receiving narasin
      had a lower mean NE score on day 17 (P > 0.05) and significantly (P < 0.05) lower
      huddling scores on days 16 and 17 than unmedicated. Coccidiosis lesion scores
      were zero for birds euthanatized from all treatment groups on day 17, suggesting
      that the beneficial effects of narasin were not due to prevention of coccidiosis.
      This study thus provides evidence that narasin is effective in the prevention of
      necrotic enteritis in broiler chickens.

PMID- 11332486
TI  - Molecular typing of infectious bursal disease virus of Israeli field and vaccine
      strains by the reverse transcription/polymerase chain reaction/restriction
      fragment length polymorphism assay.
AB  - Infectious bursal disease viruses (IBDVs) were examined by testing bursa samples
      from 37 commercially reared chicken flocks and three vaccine strains by the
      reverse transcription (RT)/polymerase chain reaction (PCR)/restriction fragment
      length polymorphism assay (RFLP). The assay was conducted with a 717-bp fragment
      of the VP2 gene with the restriction enzymes BstNI and MboI. The presence of a
      restriction site for SspI was used to predict a very virulent phenotype. Results
      indicated the existence of two molecular groups within the field isolates; four
      samples showed one pattern of RFLPs, and the majority, 30 out of the 37 tested,
      showed a second RFLP pattern. Three samples tested negative for IBDV. Eight bursa
      samples, representing the two molecular groups, were also tested by the
      RT/PCR/RFLP assay as developed by Jackwood. A comparison of the RFLP profiles by
      the two methods indicated that four isolates belonged to molecular group 6 and 30
      isolates belonged to a new molecular group. All field isolates had a very
      virulent phenotype. One vaccine strain, produced from a local isolate, was
      classified as molecular group 6. The other two vaccine strains had RFLPs that
      differed from those of the field isolates.

PMID- 11332487
TI  - Ventricular septal defect in a houbara bustard (Chlamydotis undulata macqueenii).
AB  - A ventricular septal defect was found in a juvenile captive-bred houbara bustard
      (Chlamydotis undulata) that died suddenly. The case history indicated that the
      bird had a retarded growth and maturation rate. Gross pathology demonstrated
      massive internal hemorrhage, an enlarged heart with an interventricular septal
      defect, one shrunken liver lobe, and hypoplastic kidneys. Histologically, the
      liver was characterized by fatty degeneration, and there was hydropic
      degeneration of the cardiac muscle fibers. We suggest that the occurrence of this
      defect led to cardiac insufficiency, which resulted in sudden death caused by
      hemorrhage from the liver.

PMID- 11332488
TI  - Gizzard erosion in broiler chicks by group I avian adenovirus.
AB  - Incidences of mortality without any clinical signs occurred in growing chicks in
      a broiler flock. Five 17-day-old dead broilers with gizzard erosions were
      investigated pathologically. Macroscopically, the gizzards were found to be
      dilated with bloody fluids. The koilin layer of the gizzards showed multifocal
      black patches (erosions). Histologically, there was necrosis of the koilin layer,
      degeneration and depletion of the gizzard glandular epithelium with intranuclear
      inclusion bodies, and hyperplasia of the macrophages in the lamina propria. An
      immunohistochemical analysis revealed intranuclear inclusion bodies in the
      degenerating gizzard glandular epithelial cells that stained positively for group
      I avian adenovirus antigen. Ultrastructurally, numerous viral particles (an
      average of 72 nm in diameter, from 63 to 88 nm) were in the intranuclear
      inclusions of glandular epithelium. This study suggests that the gizzard erosions
      may have been caused by group I avian adenovirus. In addition, the degeneration
      and depletion of gizzard glands secreting koilin substances, by adenovirus, may
      induce a reduction of koilin substances, which may then cause gizzard erosion
      (focal loss of the koilin layer).

PMID- 11332489
TI  - Gizzard impaction in lesser rhea chicks (Pterocnemia pennata) raised on farms in
      Patagonia, Argentina.
AB  - Impaction of the gizzard was diagnosed in 33 1-to-4-wk-old lesser rhea
      (Pterocnemia pennata) raised on farms in Patagonia, Argentina. The birds showed
      anorexia, lethargy, constipation, dehydration, weight loss, and weakness.
      Necropsy revealed gizzard impaction by fibrous material, sand, rocks, and
      rubbish. Also, excess fibrous material was observed in the small intestine, and
      intussusception was found in one chick. Impaction of the gizzard observed in the
      present study was similar to that reported in other ratite species and confirmed
      that this disease can affect lesser rhea chicks raised in captivity. This disease
      affected 33 out of 41 (80%) dead lesser rhea chicks submitted to the Animal
      Health Unit of The National Institute of Agricultural Technology, Bariloche,
      Argentina, during the study period, so it can be a significant cause of mortality
      in farmed rheas in Argentina.

PMID- 11332490
TI  - Isolation of Newcastle disease virus and Salmonella typhimurium from the brain of
      double-crested cormorants (Phalacrocorax auritus).
AB  - Avian paramyxovirus type 1 (Newcastle disease virus) and Salmonella typhimurium
      were isolated from the brain and lung tissues of double-crested cormorants
      (Phalacrocorax auritus) from Lac Canard, Alberta, Canada. More than 100 birds
      died during this outbreak in 1999. Affected birds presented signs of central
      nervous system disease characterized by unilateral wing and leg paralysis. Other
      geographic locations in the provinces of Alberta and Saskatchewan have reported
      cases of cormorants suffering from diseases with signs compatible with Newcastle
      disease. The virus isolated in the 1999 outbreak was characterized as mesogenic.
      These findings suggest that other pathogens, like S. typhimurium, may influence
      the clinical presentation of disease caused by mesogenic strains of Newcastle
      disease virus in cormorants.

PMID- 11332491
TI  - Proximal aortic dissection (dissecting aortic aneurysm) in a mature ostrich.
AB  - The gross and histopathologic lesions observed in a case of spontaneous proximal
      aortic dissection (dissecting aortic aneurysm) in a mature ostrich are reported.
      At necropsy, a dissecting intramural hematoma was seen in the proximal aorta,
      extended about 12 cm distally from the aortic valves. Histopathologic changes in
      aortic dissection included fragmentation and disruption of elastic laminae,
      presence of cystic extracellular spaces, and pooling of ground substance in the
      tunica media. Hepatic copper levels were measured, and the low concentration
      found suggested that a copper deficiency together with other risk factors such as
      the elevation of blood pressure may have been implicated in the development of
      the aortic dissection seen in this ostrich.

PMID- 11332492
TI  - Avian influenza epidemic in Italy due to serovar H7N1.
AB  - Beginning at the end of March 1999, a syndrome characterized by severe
      depression, anorexia, fever, and respiratory and enteric symptoms appeared in
      flocks of turkeys and, to a lesser extent, of chickens in the densely populated
      poultry-rearing regions of northeast Italy. The disease was characterized by
      sinusitis, tracheitis, peritonitis, and pancreatitis. The mortality varied
      between 5% and 90%. The disease was diagnosed as low pathogenic avian influenza,
      H7N1 serotype. After a summer period of declining cases, the disease reappeared
      in autumn exclusively in turkeys. Since the middle of December 1999, many farms
      of chickens, turkeys, and guinea fowl were abruptly affected by a highly
      pathogenic H7N1 virus, with very severe depression and mortality up to 100% in a
      few days. By the end of March 2000, nearly 500 farms, representing over 15
      million birds, were affected or depopulated. To date, control measures have
      focused on improved biosecurity measures. Vaccine was not allowed, but its use
      was debated.

PMID- 11332493
TI  - Detection of infectious bursal disease virus in experimentally infected chickens
      by in situ hybridization.
AB  - In situ hybridization was used in a pathogenesis study of three vaccine
      pathotypes (Delaware variant A, D78, and BursaVac) of infectious bursal disease
      virus (IBDV). Tissues were excised (bursa, thymus, spleen, proventriculus, and
      cecal tonsils), fixed in formalin, and paraffin embedded at 12, 24, 48, 72, and
      120 hr postinoculation (HPI). With an antisense VP2 gene probe, viral nucleic
      acid was detected in bursas from both D78- and BursaVac-infected chickens at 24,
      48, 72, and 120 HPI. However, viral RNA was detected only in the Delaware variant
      A-infected birds at 72 HPI. Thymus and spleen were positive in the D78-infected
      birds at 48 HPI and in the BursaVac-inoculated group at 72 HPI. Viral nucleic
      acid was not present in detectable levels among any of the tissues tested at 12
      HPI. However, by 24 hr, scattered positive lymphoid cells were visualized in the
      bursal follicles of chickens infected with D78 and BursaVac. In addition, low
      levels of viral nucleic acids were detected in the thymus and spleen among the
      D78- and BursaVac-infected birds. The sites of viral replication were consistent
      between the two vaccine-infected groups (D78 and BursaVac), whereas the chickens
      infected with Delaware variant A had limited IBDV replication in the bursa.

PMID- 11332494
TI  - Ocular and encephalic toxoplasmosis in canaries.
AB  - In this report we describe the lesions produced by the protozoal organism,
      Toxoplasma gondii, in the eyes and brain of the common yellow canary (Serinus
      canaria). Nine of 15 birds in a flock were affected with blindness, which
      developed over a 3-mo span, and two birds developed torticollis. Microscopic
      alterations within the eye consisted of a nonsuppurative chorioretinitis with
      large numbers of macrophages that contained the tachyzoite form of T. gondii in
      the subretinal space, and aggregates of tachyzoites were found in the nerve fiber
      layer of the retina with and without necrosis. Tissue cysts with bradyzoites were
      scattered throughout the meninges and neuropil of the cerebrum and cerebellum.
      Both forms were confirmed by transmission electron microscopy in the eye and
      brain. Frozen brain samples reacted with T. gondii-specific cat sera in indirect
      fluorescent antibody tests. The source of infection was hypothesized to be from a
      stray cat the owner kept that had access to some of the bird feed. Treatment
      (trimethoprim 0.08 g/ml H2O and sulfadiazine 0.04 g/ml in water for 2 wk) was
      instituted by the referring veterinarian on the remaining birds. A second
      treatment regime was given for 3 wk. The owner of the canaries did not return for
      further treatment.

PMID- 11332495
TI  - Epizootic outbreaks of gizzard erosion associated with adenovirus infection in
      chickens.
AB  - Two outbreaks of gizzard erosion in slaughtered broiler chickens in Japan were
      examined pathologically and microbiologically. The prevalences of such lesions
      were 9%-11% and 4%-50% in the affected flocks. Affected chickens had no clinical
      signs. Group I fowl adenovirus (FAV) serotype 1 was isolated from gizzard
      lesions. Histologically, gizzard mucosa were necrotic. Intranuclear inclusion
      bodies were seen in the enlarged nuclei of degenerating epithelial cells of the
      gizzard. The keratinoid layer in the erosion was edematous and desquamated and
      contained degenerative cells. Moderate to marked inflammatory cell infiltration
      was observed in the lamina propria and perivascular connective tissue in the
      submucosa and muscle layer. Immunohistochemical staining showed evidence of FAV
      antigens in the intranuclear inclusion bodies within degenerating epithelial
      cells. Ultrastructurally, numerous viral particles were demonstrated in the
      inclusions.

PMID- 11332496
TI  - Atypical parasitic migration and necrotizing sacral myelitis due to
      Serratospiculoides amaculata in a prairie falcon (Falco mexicanus).
AB  - An adult, wild-caught, female prairie falcon (Falco mexicanus) was presented with
      the chief complaint of anorexia. Radiographic findings included increased
      densities within the air sacs, and coelomic endoscopy revealed numerous slender
      worms within the air sacs and on the serosal surfaces of the ovary, oviduct,
      liver, proventriculus, and ventriculus. The bird seemed to improve for a short
      period of time with antiparasitic therapy (ivermectin and fenbendazole) and
      supportive care. Twenty-one days after initial presentation, the bird became
      recumbent with increasing pelvic limb neurologic deficits and was euthanized. On
      histopathologic examination, mature nematodes and larvated eggs identified as
      Serratospiculoides amaculata were found within the subdural space of the distal
      thoracolumbar and synsacral spinal cord and within the coelomic cavity. This case
      suggests that S. amaculata can cause clinically significant lesions in its
      falconiform host with potentially fatal results.

PMID- 11332497
TI  - Characterization of nine Pasteurella multocida isolates from avian cholera
      outbreaks in Indonesia.
AB  - Avian cholera outbreaks have been identified in Indonesia in recent years.
      Despite vaccination programs, outbreaks continue to occur. To date, there has
      been a lack of information on the characteristics of Pasteurella multocida
      isolates involved in these outbreaks. Hence, the objective of this study was to
      characterize Indonesian P. multocida isolates in poultry. During 1998-99, 20
      field outbreaks were reported in Indonesia. Nine isolates of P. multocida were
      recovered from these field outbreaks. The isolates were compared with four
      vaccine strains that were used in Indonesia and designated PM-V1, PM-V2, PM-V3,
      and PM-V4. The isolates were characterized by biotype, capsular type, somatic
      serotype, restriction endonuclease analysis, plasmid presence, and antimicrobial
      susceptibility patterns. Of the nine Indonesian isolates, three were of capsular
      type A (A:1,3,13; A:1,3; and A:8). One isolate was of type B:2,3 and one isolate
      was of capsular type F. For three isolates, the capsular serogroup could not be
      identified. Plasmids the size of 2.3 kbp were present in three of the field
      isolates and two of the vaccine strains. One plasmid less than 2 kbp was isolated
      from the vaccine strain PM-V4. Eight distinct DNA profiles were obtained from
      digestion with the restriction endonuclease EcoRI, and seven distinct DNA
      profiles were obtained from digestion with the restriction endonuclease HindIII.
      All of the isolates were resistant to lincomycin and sulfadiazine and were
      susceptible to ampicillin and trimethoprim. Of the nine isolates, seven (78%)
      were susceptible to doxycycline and gentamicin and six (67%) were susceptible to
      enrofloxacin.

PMID- 11332498
TI  - Vacuolating cytotoxin produced by avian pathogenic Escherichia coli.
AB  - The purpose of this study was to determine whether avian pathogenic Escherichia
      coli produced cytotoxic activity. Culture supernatants of 20 E. coli strains
      isolated from cellulitis lesions in chickens, five E. coli strains from avian
      septicemia, five from swollen head syndrome, and five from the feces of healthy
      chickens were incubated with primary chicken embryo fibroblast (CEF) cells,
      primary chicken kidney (PCK) cells, a quail fibroblast cell line (QT-35), and
      four mammalian cell lines (human epithelioid cervical carcinoma, African green
      monkey kidney, Chinese hamster ovary, and human larynx epidermoid carcinoma).
      Cytotoxicity was observed with supernatants from the 30 avian pathogenic strains
      on the two primary chicken cells (CEF and PCK). The highest dilution of culture
      supenatant that induced cytotoxic changes in 50% of the cells was 1/64.
      Supernatants from the five strains from normal feces were noncytotoxic, and none
      of the supernatants was cytotoxic for the QT-35 or the four mammalian cell lines.
      The cytotoxic effect, which was observed as early as 2 hr after exposure of the
      cells, was maximal at 6 hr and was evident as vacuolation, morphologically
      indistinguishable from that previously reported for culture supernatants of
      Helicobacter pylori. Like the activity in H. pylori, the cytotoxicity of the
      avian pathogenic strains was destroyed by heating at 70 C for 30 min and by
      exposure to proteolytic enzymes and was retained by filtration with a 100,000
      molecular weight cut-off ultrafilter. Supernatants of two vacuolating cytotoxin
      positive cultures of H. pylori failed to induce vacuolation of the CEF and PCK
      cells but caused the characteristic vacuolation in HeLa and Vero cells. The
      observations suggest that avian pathogenic E. coli produce a cytotoxin that is
      similar to the cytotoxin of H. pylori but may be specific for avian cells.

PMID- 11332499
TI  - The exacerbating effect of infectious bronchitis virus infection on the
      infectious bursal disease virus-induced suppression of opsonization by
      Escherichia coil antibody in chickens.
AB  - Chickens infected with infectious bronchitis virus (IBV) and infectious bursal
      disease virus (IBDV) commonly develop secondary infection of the respiratory
      tract with Escherichia coli, resulting in significant economic losses. To
      understand the host factors that may contribute to the E. coli infection, we
      investigated macrophage-mediated E. coli phagocytosis, intracellular bacterial
      killing, and development of opsonizing antibody in previously uninfected chickens
      and in those infected with IBV, IBDV, and IBDV plus IBV. Macrophages from the
      peripheral blood and the respiratory tracts of chickens infected with IBV or IBDV
      plus IBV efficiently performed in vitro phagocytosis of E. coli in the presence
      of positive-control serum (i.e., E. coli antiserum produced in normal chickens).
      Those macrophages also had adequate bactericidal activity, indicating that IBV
      and IBDV infections had not affected their phagocytic activity or bactericidal
      function. The phagocytic activity of macrophages remained unaffected (P < 0.05)
      when the positive-control serum was replaced with E. coli antiserum produced in
      chickens infected with IBV alone. However, when E. coli antisera raised in IBDV
      infected and, especially, that produced in IBDV plus IBV-infected chickens were
      supplemented, the percentage of phagocytosis and number of bacteria ingested per
      phagocyte were significantly (P < 0.05) less. These results indicate that
      although IBDV alone has the potential to markedly reduce opsonizing ability of
      antibody, this effect is significantly (P < 0.05) exacerbated by IBV infection.

PMID- 11332500
TI  - Differences among six Salmonella serovars in abilities to colonize reproductive
      organs and to contaminate eggs in laying hens.
AB  - The abilities of Salmonella serovars to colonize the reproductive organs of
      chickens and to contaminate eggs were compared. Mature laying hens were
      inoculated intravenously with 10(5) colony-forming units of Salmonella
      enteritidis, Salmonella typhimurium, Salmonella infantis, Salmonella hadar,
      Salmonella heidelberg, or Salmonella montevideo to cause the systemic infection.
      Salmonella enteritidis was recovered from three yolks of the laid eggs (7.0%),
      suggesting egg contamination from the transovarian transmission of S.
      enteritidis. The liver, spleen, and cecum were colonized by each serovar
      similarly at 4 or 7 days postinoculation (PI), whereas the ovary and preovulatory
      follicles were colonized by S. enteritidis with significantly (P < 0.05) higher
      levels than by the other serovars at 4 and 7 days PI. Salmonella enteritidis was
      recovered from the cloaca and vagina at 2, 4, and 7 days PI and from the other
      portions of the oviduct at 4 and 7 days PI. In addition, S. enteritidis had been
      persistent in the peripheral blood for 7 days PI. These results suggest that S.
      enteritidis is the predominant serovar to colonize the reproductive organs of
      mature laying hens among six serovars used in this study, reflecting the field
      situatibn in which the predominant outbreaks of human salmonellosis were caused
      by S. enteritidis-contaminated eggs recently. The ability of S. enteritidis to
      colonize the reproductive organs may be one of the reasons that egg contamination
      with S. enteritidis has increased.

PMID- 11332501
TI  - Characterization of mycoplasma gallisepticum infection in captive house finches
      (Carpodacus mexicanus) in 1998.
AB  - Since 1995, the epidemic of mycoplasmal conjunctivitis in eastern house finches
      has affected the Auburn, AL, house finch population. To better characterize the
      current status of this host-parasite interaction, we established a captive flock
      of 38 seronegative, healthy finches in fall 1998. After a minimum quarantine
      period of 4 wk, two Mycoplasma gallisepticum (MG)-infected house finches were
      introduced into this flock. Over a 12-wk period, the flock was captured every 2
      wk and each bird was observed for conjunctivitis. Blood and choanal swabs were
      collected from each bird for serologic analysis and for the detection of MG by
      polymerase chain reaction. The infection spread rapidly through the flock just as
      it had in a similar study performed in 1996 at the height of the epidemic. Unlike
      the earlier study in which birds remained chronically infected, most of the birds
      in our study recovered rapidly, and only three of the birds died during the
      study. Two patterns of host response to infection with MG were observed. Twenty
      seven birds (73%) experienced an acute conjunctivitis that resolved, and the
      birds appeared to clear the infection. Ten birds (27%) suffered prolonged
      clinical disease, and MG could be detected in these birds intermittently
      throughout the experiment. These results, in conjunction with our surveys of MG
      in the wild population, suggest an evolving host-parasite interaction.

PMID- 11332502
TI  - Inactivation of an astrovirus associated with poult enteritis mortality syndrome.
AB  - Outbreaks of poult enteritis mortality syndrome (PEMS) continue to cause
      financial losses to the turkey industry. Clinically, PEMS is defined by mortality
      profiles, diarrhea, flock unevenness, and immunosuppression. PEMS is a very
      difficult disease to control and prevent. Depopulation of PEMS-affected flocks
      and thorough cleaning of the contaminated housing have failed to prevent
      infection (disease) in subsequent flock placements. The relationship of PEMS to
      other enteric disease complexes of young turkeys is unknown, partly because the
      causative agent of PEMS remains unknown. Recently, we isolated a unique
      astrovirus strain from the thymus and intestines of PEMS-infected poults. This
      strain is molecularly and serologically distinct from the astrovirus that
      circulated in turkeys in the 1980s. Mammalian astroviruses are very resistant to
      inactivation. In these studies, we examined the stability of partially purified
      PEMS-associated astrovirus to inactivation with heat, laboratory disinfectants,
      and commercial disinfectants used in commercial turkey houses in an embryonated
      egg model system. Similar to mammalian astroviruses, the PEMS-associated
      astrovirus is resistant to inactivation by heat, acidification, detergent
      treatment, and treatment with phenolic, quaternary ammonium, or benzalkonium
      chloride-based products. Only treatment with formaldehyde, beta-propriolactone,
      or the peroxymonosulfate-based product Virkon S completely inactivated the
      astrovirus in the embryo model. These studies provide an alternate means to
      potentially control at least one virus associated with PEMS through the use of
      specific disinfectants.

PMID- 11332503
TI  - Vaccination against Salmonella enteritidis in Dutch commercial layer flocks with
      a vaccine based on a live Salmonella gallinarum 9R strain: evaluation of
      efficacy, safety, and performance of serologic Salmonella tests.
AB  - This study describes a field trial in which 80 commercial layer flocks, with an
      increased risk of Salmonella enteritidis (SE) infection and placed on farms with
      a certified Standardized Biosecurity Programme (SBP) or a request for a SBP
      certificate, were vaccinated with a vaccine based on a live attenuated Salmonella
      gallinarum (SG) 9R strain. An evaluation is presented of the efficacy of the
      vaccine against SE infections, the effect on the performance of serologic
      Salmonella tests, and the spread of the vaccine strain to the egg content. For
      the efficacy study, assessment of the flock level occurrence of SE infections in
      the vaccinated group of 80 flocks was compared with that of a nonvaccinated group
      of 1854 flocks hatched in the same period. This control group was examined
      according to the compulsory control programme in The Netherlands. An evaluation
      was done of the performance of serologic Salmonella tests and the spread of the
      vaccine strain to the inner egg content of five of the vaccinated flocks.
      Findings demonstrated the flock level occurrence of SE infections in the
      vaccinated group (2/80 = 2.5%) to be significantly (P = 0.01) lower than that of
      the nonvaccinated group (214/1854 = 11.5%). Vaccination resulted in 59.0%
      positive test results in lipopolysaccharide BD enzyme-linked immunosorbent assay
      (ELISA) for detecting antibodies against Salmonella serogroups B and D and 0%
      positive test results in the rapid plate agglutination test for detecting
      antibodies against S. pullorum (SP)/SG. The mean specificities of two blocking
      ELISAs (gm- and i-double antibody sandwich ELISAs) based on the flagellar antigen
      of SE and Salmonella typhimurium (ST) on the same sera were 99.6% and 96.1%,
      respectively. The vaccine strain could not be isolated from any of the 450 pools
      of 10 eggs. On the basis of these results, we concluded that vaccination with a
      vaccine based on an attenuated SG 9R strain contributes to the reduction of SE
      infections in commercial layer flocks. Furthermore, serologic monitoring of SE,
      ST, and SP/SG can still be carried out on flocks vaccinated with an attenuated SG
      9R strain. Additionally, we found no indication of the spread of the vaccine
      strain to the egg content.

PMID- 11332504
TI  - Coinfection of specific-pathogen-free chickens with Marek's disease virus (MDV)
      and chicken infectious anemia virus: effect of MDV pathotype.
AB  - Both Marek's disease virus (MDV) and chicken infectious anemia virus (CIAV)
      infections are prevalent in chickens throughout the world. In the past decade,
      MDV strains with increased virulence (very virulent plus MDV pathotype [vv+MDV])
      have been isolated. The purpose of this experiment was to determine the effects
      of coinfection of chickens with CIAV and a vv+MDV isolate. Specific-pathogen-free
      chickens were inoculated at 1 day posthatch with RB1B (very virulent MDV
      pathotype [vvMDV]) only, 584A (vv+MDV) only, CIAV only, RB1B + CIAV, 584A + CIAV,
      or nothing. Samples of spleen, thymus, and bursa of Fabricius were collected at
      4, 7, 10, and 13 days postinoculation (DPI). Thymic and bursal atrophy at 13 DPI
      and final mortality at 30 DPI were significantly greater in chickens inoculated
      with 584A with or without added CIAV, or with RB1B plus CIAV, compared with birds
      inoculated with RB1B alone. Both amounts of virus reisolated and levels of virus
      detected by quantitative-competitive polymerase chain reaction were greater at 4
      DPI in 584A inoculates compared with RB1B inoculates. To monitor the early
      cytolytic infection, northern analysis was done with a probe for the MDV
      immediate early gene ICP4 (infected cell protein 4). In the absence of CIAV, ICP4
      expression was more apparent in chickens inoculated with 584A than in those
      inoculated with RB1B. CIAV coinfection increased ICP4 expression in the spleens
      of chickens infected with RB1B. These results indicated that inoculation of
      chickens with the 584A isolate caused a more robust early cytolytic infection
      compared with inoculation with RB1B alone and support the classification of 584A
      as a vv+MDV strain. Coinfection with CIAV exacerbated vvMDV strain RB1B
      infection. The extent of this exacerbation was less evident when birds were
      coinfected with 584A and CIAV.

PMID- 11332505
TI  - Immunogenicity and antigenicity of very virulent strains of infectious bursal
      disease viruses.
AB  - The immunogenicity and antigenicity of three very virulent (vv) strains of
      infectious bursal disease viruses (IBDVs) from Turkey (OA), Holland (HOL), and
      Taiwan (PT) were investigated, and their antigenic relationships with the
      American classic SAL, variant IN serotype 1, and serotype 2 OH IBDVs were
      studied. In the present study, the vvIBDVs were passaged eight times in chicken
      embryos and were characterized by reverse transcription/polymerase chain reaction
      restriction fragment length polymorphism with restriction enzymes MboI and BstNI.
      The restriction fragment length polymorphism profile patterns of these viruses
      did not change after eight passages in chicken embryos. Attempts were
      unsuccessful in adapting the vvIBDVs to replicate in vitro after six passages in
      primary cell cultures of chicken (chicken embryo fibroblast cells, chicken kidney
      embryo cells, and chicken embryo bursal cells), five passages in established cell
      lines (LSCC-RP9 and LSCC-RP12 B-lymphoblastoid cells, chicken macrophage [MQ
      NCSU] cells, quail [QT35] cells), and 10 passages in vero and BGM-70 cells.
      Because it was not possible to adapt the vvIBDVs to cell culture, the antigenic
      relatednesses between these viruses and the American strains were established by
      cross-neutralization tests in chicken embryos, and the relatedness values were
      calculated with the Archetti and Horsfall formula. The results revealed that the
      vvIBDVs are antigenically related to the classic SAL strain but are antigenically
      different from the variant IN strain and serotype 2 OH virus. For the
      immunogenicity study, inactivated vaccines prepared from the vvIBDVs and
      containing 10(5) mean embryo lethal dose of each virus induced different levels
      of protection. The vaccines provided full protection against the classic STC
      strain but provided no protection against the variant IN strain at 5 and 10 days
      postchallenge.

PMID- 11332506
TI  - Adult neurogenesis in natural populations.
AB  - The dogma that the adult brain produces no new neurons has been overturned, but
      the critics are still asking, so what? Is adult neurogenesis a biologically
      relevant phenomenon, or is it perhaps harmful because it disrupts the existing
      neuronal circuitry? Considering that the phenomenon is evolutionarily conserved
      in all mammalian species examined to date and that its relevance has been well
      documented in non-mammalian species, it seems self-evident that neurogenesis in
      adult mammals must have a role. In birds, it has been established that
      neurogenesis varies dramatically with seasonal changes in song production. In
      chickadees, the learning behaviour related to finding stored food is also
      correlated with seasonal adult neurogenesis. Such studies are still nonexistent
      in mammals, but the related evidence suggests that neurogenesis does vary
      seasonally in hamsters and shows sexual differences in meadow voles. To promote
      studies on natural populations asking fundamental questions of the purpose and
      function of neurogenesis, we organized a Workshop on "Hippocampal Neurogenesis in
      Natural Populations" in Toronto in May 2000. The Workshop highlighted recent
      discoveries in neurogenesis from the lab, and focused on its functional
      consequences. The consensus at the Workshop was that demonstration of a role for
      neurogenesis in natural behaviours will ultimately be essential if we are to
      understand the purpose and function of neurogenesis in humans.

PMID- 11332507
TI  - Vagal afferent activity and body temperature in 3 to 10-day-old and adult rats.
AB  - This study examined the possible contribution of vagal stretch receptor activity
      to the increased power of the Hering-Breuer reflex in hyperthermia in rats during
      the early postnatal period. Experiments were performed on 10 anesthetized
      (pentobarbital 40 mg/kg, i.p.) 3 to 10-day-old (body weight of 16 +/- 1 g; SE)
      and, for comparison, 18 adult Sprague-Dawley rats (body weight of 336 +/- 35 g).
      Animals were tracheostomized and artificially ventilated with oxygen. The left
      vagus nerve was cut. In adult animals, single receptor fibers or a bundle of a
      few fibers were recorded using a bipolar stainless-steel electrode under mineral
      oil. In the young rats, a suction electrode filled with normal saline was used.
      Positive pressure of either 5 or 10 cmH2O was applied to the trachea when the
      respirator was turned off. The vagal activity was amplified and monitored on a
      storage oscilloscope for calculation of the frequency of vagal afferent activity
      during a given pressure application at different rectal temperatures (T(R); range
      28 to 42 degrees C). In total, 30 and 31 sets of vagal activity in the young and
      adult rats, respectively, were analyzed. In all cases, an increase in tracheal
      pressure (P(TR)) from 5 to 10 cmH2O increased the frequency of vagal firing. The
      increase was greater in the adult versus the young animals; at 36 degrees C the
      increase was 49 +/- 11% and 16 +/- 3% in the adult and young rats, respectively
      (P < 0.01). In all animals, vagal receptors showed temperature-sensitivity, but
      less so in the young than in the adult rats (P < 0.0004 and P < 0.003; for P(TR)
      of 5 and 10 cmH2O, respectively). In addition, the relationship between
      temperature-sensitivity and T(R) had significant slopes (P < 0.001 for both
      inflation pressures) in the adults but not in the young rats, indicating that in
      the latter the temperature-sensitivity of vagal receptors is independent of TR.
      These results imply that temperature-sensitivity of vagal receptors could have
      contributed to the increased power of the Hering-Breuer reflex in rats during the
      early postnatal period in the warmer environment.

PMID- 11332508
TI  - Functional properties of the native type 3 ryanodine receptor Ca2+-release
      channel from canine diaphragm.
AB  - mRNA and protein analyses have previously shown that the diaphragm expresses two
      ryanodine receptor isoforms: RyR1 and RyR3. RyR1 is the main Ca2+-releasing
      pathway in this muscle type. We now report the conducting, gating, and
      immunological properties of the native and purified forms of the less abundant
      RyR3 channel. The conductance of this native Ca2+-release channel was 330 pS in
      50 mM/250 mM trans/cis CsCH3SO3. It was activated by Ca2+ concentrations of 1
      1000 microM, and did not inactivate at mM concentrations of Ca2+. Both isoforms
      were purified by either a sucrose density gradient or immunoprecipitation as >
      450 kDa proteins on SDS-PAGE. Western blot analysis confirmed the presence of
      RyR1 and RyR3, which displayed conductances of 740 +/- 30 and 800 +/- 25 pS,
      respectively, in 250 mM KCl. We thus provide evidence that one form of the
      diaphragm SR Ca2+-release channels may be classified as RyR3, with gating
      properties different from those of the well-characterized RyR1 and RyR2 isoforms.

PMID- 11332509
TI  - The effects of alpha-lactabumin and whey protein concentrate on dry matter
      recovery, TCA soluble protein levels, and peptide distribution in the rat
      gastrointestinal tract.
AB  - The effects of two dietary proteins on dry matter recovery, trichloroacetic acid
      (TCA) soluble protein concentration, and peptide distribution in gastrointestinal
      contents were investigated in rats trained to consume, in a single 2-hour daily
      meal, diets containing alpha-lactalbumin (alpha-LA) or whey protein concentrate
      (WPC) for two weeks. Compared with the WPC diet, the alpha-LA diet emptied faster
      from the stomach. Dry matter recovery was higher in the stomach contents of rats
      fed the WPC diet than in those given the alpha-LA diet, but dry matter content in
      the small intestine was comparable. TCA soluble protein levels in the stomach and
      the small intestinal contents were also significantly (P < 0.001) higher in rats
      fed the WPC diet. The concentration of peptides having molecular weights (MW)
      ranging from 12,500-30,000 daltons (Da) was higher in the stomach contents of
      rats fed the WPC diet. Conversely, the level of peptides ranging from 5000-12,500
      Da was higher in the stomach contents of rats fed the alpha-LA diet. For both
      diets, the small intestinal contents were characterized by high levels of amino
      acids and small peptides. These results suggest that the hydrolysis and
      absorption of alpha-LA is faster than that of WPC.

PMID- 11332510
TI  - Hemodynamic and histomorphometric characteristics of dilated cardiomyopathy of
      Syrian hamsters (Bio TO-2 strain).
AB  - The natural history of the disease of the dilated strain Bio TO-2 of
      cardiomyopathic hamsters (CMH) is not totally characterized. We investigated its
      hemodynamic and histomorphometric characteristics at 140, 180, 220, 260, and 300
      days of age. Forty CMH and 40 controls were investigated (8 at each stage). Mean
      arterial pressure (MAP, carotid artery catheter) and cardiac output and femoral
      blood flow (CO, FBF, transit time method) were measured in anesthetized animals.
      Systemic (SVR) and femoral (FVR) vascular resistances were calculated. Atria,
      left and right ventricles (LV, RV), lungs, and liver were weighed. LV cavity
      area, LV and RV wall thicknesses and collagen densities were determined (computer
      assisted image analyzer). Pulmonary and hepatic congestion were assessed
      (arbitrary scales). Compared with controls, MAP, CO and FBF were significantly
      lower in CMH throughout the study (on average: -22%, -34%, -33%, respectively),
      FVR was significantly increased (+15%), but SVR was not significantly modified.
      Concerning histomorphometric characteristics, differences between groups
      significantly increased with age for most variables: at 300 days, atria (+292%),
      RV (+13%), lungs (+44%), and liver (+23%) weights, LV cavity area (+130%), LV
      (+364%) and RV (+181%) collagen densities were significantly increased in CMH vs
      controls, whereas LV (-40%) and RV (-23%) wall thicknesses were significantly
      decreased. At 260 and 300 days, CMH showed significant pulmonary congestion
      without hepatic alteration. Bio TO-2 CMH progressively develop an alteration of
      cardiac function leading to decreased MAP and musculo-cutaneous blood flow
      associated with cardiac remodeling including atria hypertrophy and LV dilation,
      wall thinning and a rise in collagen density.

PMID- 11332511
TI  - Eicosatetraynoic acid (ETYA), a non-metabolizable analogue of arachidonic acid,
      blocks the fast-inactivating potassium current of rat pituitary melanotrophs.
AB  - The effects of arachidonic acid (5,8,11,14-eicosatetraenoic acid, AA) and
      5,8,11,14-eicosatetraynoic acid (ETYA), a non-metabolizable analogue of AA, were
      examined on the transient [I(K)(f)] and the delayed rectifier-like [I(K)(S)]
      voltage-gated potassium currents in rat pituitary melanotrophs. The main
      questions addressed were whether AA and ETYA blocked I(K)(f) and if any blocking
      action was specific. Macroscopic currents were measured using the patch clamp
      technique. Bath application of 20 microM AA reduced I(K)(f), however, the degree
      of the block varied between cells. In contrast, ETYA consistently inhibited
      I(K)(f). Fitting of the charge transfer or the peak current amplitude yielded KD
      estimates for ETYA of 1.2 microM and 3.3 microM, respectively. The reduction by
      ETYA of peak I(K)(f) was always associated with an increased rate of current
      decay, but there was no detectable change of the kinetics of activation. ETYA
      caused a small left shift of the I(K)(f) steady-state inactivation curve and
      significantly slowed recovery from inactivation. At 20 microM, ETYA also reduced
      I(K)(s), indicating that it is not specific. The possibility that ETYA acts as an
      open-channel blocker is discussed.

PMID- 11332514
TI  - Insulin-like peptides are not involved in maturation or functional recovery of
      neural circuits in the locust flight system.
AB  - We sought to manipulate maturation and functional recovery of locust flight
      circuitry by treating locusts with pharmacological doses of bovine anti-insulin
      and insulin. Anti-insulin treatment of maturing locusts caused reduced growth of
      the thoracic nervous system, lower body weight, and softer cuticles compared with
      control locusts. We were unable to block either maturation or recovery of flight
      circuitry with anti-insulin. We propose that insulin-related peptides are
      involved in growth and cuticular changes during adult maturation, but have no
      role in promoting neuronal sprouting during this period or as a result of injury.

PMID- 11332513
TI  - Effect of exogenous growth hormone on somatic growth, gonadal development, and
      hepatic CYP2C11 and CYP2C12 expression in prepubertal intact male rats.
AB  - The influence of exogenous growth hormone (GH) on pubertal maturation, as
      assessed by growth, age of preputial separation, testicular development, and
      hepatic expression of sexually dimorphic cytochrome P450 (CYP) enzymes, was
      investigated. Treatment of 22-day old prepubertal intact male rats with twice
      daily subcutaneous (s.c.) injections of rat recombinant GH (0.12 microg/g body
      weight) for 12 or 21 days did not affect body weight, skeletal growth, or
      testicular weight. By comparison, GH suppressed hepatic CYP2C1 enzyme activity,
      protein, and mRNA levels but induced CYP2C12 expression. GH suppressed CYP2C11
      expression by approximately 60% in prepubertal rats as compared with 30% in adult
      rats, whereas it increased CYP2C12 levels to 80% of the normal female levels but
      had no effect in adult male rats. Twice daily intravenous injections of GH
      suppressed CYP2C11 only. Increasing the s.c. dose of GH 30-fold produced little
      or no additional change in CYP2C11 or CYP2C12 expression, whereas it modestly in
      creased body weight and skeletal growth and reduced testicular weight. Overall,
      the present study provides the first demonstration that prepubertal
      administration (22-33 days of age) of GH at a pharmacologically relevant dose
      (0.12 microg/g twice daily) suppressed hepatic expression of CYP2C11 in 34-day
      old intact male rats, suggesting that in this age group the liver is
      intrinsically responsive to transcription factors involved in the regulation of
      GH-dependent, sex-specific CYP gene expression. A higher dose (3.6 microg/g) of
      GH administered during the prepubertal period was required to elicit a modest
      effect on somatic growth and gonadal development.

PMID- 11332512
TI  - Diabetes reduces right atrial beta-adrenergic signaling but not agonist
      stimulation of heart rate in swine.
AB  - This study assessed the effects of streptozotocin diabetes in swine on the heart
      rate response to beta-adrenergic stimulation the adenylyl cyclase signal
      transduction pathway. Diabetic animals (n = 9) were hyperglycemic compared to the
      control group (n = 10) (12.6 +/- 1.0 vs. 3.53 +/- 0.29 mM). There were no
      significant differences between the diabetic and nondiabetic groups in the heart
      rate response to isoproterenol, however, there was a significant reduction (14%)
      in beta-adrenergic receptor density in the right atrium in the diabetic (61 +/- 3
      fmol/mg protein) versus the nondiabetic group (71 +/- 3) (P < 0.05). The content
      of guanosine triphosphate binding regulatory proteins (Gs and Gi) in the right
      atrium was not affected by diabetes, nor was adenylyl cyclase activity under
      unstimulated conditions or with receptor-dependent stimulation with
      isoproterenol. On the other hand, adenylyl cyclase activity was 34% lower when
      directly stimulated with forskolin, and it was reduced by 23% when stimulated
      through Gs with Gpp(NH)p. In conclusion, beta-adrenergic stimulation of heart
      rate with isoproteronol and the receptor-dependent signal transduction pathway
      remained intact in the right atrium of diabetic swine despite reduced beta
      adrenergic receptor density, G-protein content, and direct stimulation of
      adenylyl cyclase activity.

PMID- 11332515
TI  - The Aplysia californica Cl- pump is a P-type ATPase: evidence through inhibition
      studies.
AB  - Utilizing a proteoliposomal preparation containing Cl(-)-ATPase from Aplysia
      californica foregut, it was shown that orthovanodate inhibited Cl(-)-ATPase
      activity, ATP-dependent Cl- transport, ATP-dependent membrane potential change
      and ATP-dependent phosphorylation. N-ethylmalemide and p-chloromercurobenzoate
      also inhibited the Cl- pump biochemical and physiological transport
      characteristics. However, bafilomycin, azide, N, N'-dicyclohexylcarboiimide
      (DCCD), and efrapeptin had no effect on the Cl- pump biochemical or physiological
      characteristics, suggesting that this Cl- pump was a P-type ATPase. It was
      concluded that this P-type ATPase Cl- pump is the mechanism that is responsible
      for the net absorptive flux of Cl- in the A. californica foregut.

PMID- 11332516
TI  - Aging affects hemispheric asymmetry on a competing speech task.
AB  - This study examined the effects of aging on the hemispheric asymmetry of event
      related potentials (ERPs) evoked by morphosyntactic anomalies in a competing
      speech paradigm. The experimental groups consisted of children, young adults, and
      elderly persons. The ERPs were recorded from 32 scalp sites while participants
      listened to a continuous narrative presented quasidichotically via loudspeakers.
      Participants responded when they heard an anomalous word embedded within a
      popular fairy tale. Anomalous words evoked a robust positivity in the 700- to 900
      msec latency range in all participants. Comparison of area measures from
      waveforms at the lateral frontal, frontotemporal, temporal, temporoparietal, and
      parietal electrode sites revealed asymmetry in hemispheric positivity. In
      children and young adults, asymmetry peaked in the 600- to 800-msec range and
      favored the left hemisphere in both target-right and target-left conditions. In
      seniors, however, asymmetry peaked at 1100 msec, favored the left hemisphere in
      the target-right condition, and favored the right hemisphere in the target-left
      condition. These results support the concept that aging affects hemispheric
      asymmetry during linguistic processing.

PMID- 11332517
TI  - Electrical status epilepticus in slow wave sleep: prospective case study of a
      cortical hearing impairment.
AB  - The development of a central hearing impairment is described in a young girl with
      risk factors for hearing impairment that included mosaic Down syndrome, leukemia,
      and chemotherapy. This case is unusual in the prospective regularity with which
      hearing was assessed from birth. The diagnosis is electrical status epilepticus
      in slow wave sleep, a rare childhood disorder, which was associated with lack of
      responsiveness to auditory signals, regression of emerging speech and language
      and other cognitive skills, and abnormal electroencephalographic (EEG) activity
      in both hemispheres. Treatment of the disorder with anticonvulsant medications
      and steroids has ameliorated the condition by suppressing the abnormal EEG
      activity and allowing substantial improvements in cognitive and social skills,
      although communication skills are improving more slowly.

PMID- 11332518
TI  - The severely to profoundly hearing-impaired population in the United States:
      prevalence estimates and demographics.
AB  - This study informs policy makers and third-party payers of the prevalence and
      characteristics of the severely to profoundly hearing-impaired population in the
      United States. Nationally representative data were used for estimations in
      consultation with an expert advisory panel. The prevalence of severe to profound
      hearing impairment among the US population ranges from 464,000 to 738,000, with
      54 percent of this population over age 65 years. Persons with hearing impairment
      are more likely to be publicly insured, less likely to have private insurance,
      have lower family incomes, are less educated, and are more likely to be
      unemployed than the general population. Approximately half a million Americans
      are severely to profoundly hearing impaired and appear to be more vulnerable,
      both financially and educationally, as compared to the US population. As a
      result, access to medical and technological interventions that may assist their
      hearing loss may be limited.

PMID- 11332519
TI  - Paired-comparison hearing aid preferences: evaluation of an unforced-choice
      paradigm.
AB  - Fifteen normal-hearing listeners compared nine frequency-response slopes in a
      round-robin paired-comparison tournament as they listened to passages of
      connected discourse against a competing noise background at a +3-dB signal-to
      noise ratio. All participants listened in an AB paradigm, in which they were
      forced to choose which of two signals (A or B) produced better speech
      intelligibility, and an ABN paradigm, in which they were allowed a third choice
      of No Preference (N). For both paradigms, listeners generally preferred frequency
      shaping that either cut low frequencies or boosted high frequencies, and intra-
      and intersession reliability was high overall. Although listeners' most-preferred
      responses tended to converge on the same frequency-response slope in the two
      paradigms, the reliability of these responses was significantly higher for ABN
      than for AB. The use of the ABN paired-comparison paradigm deserves further
      study, therefore, as a method to fit multimemory hearing aids.

PMID- 11332520
TI  - Efficacy of directional microphone hearing aids: a meta-analytic perspective.
AB  - The literature suggests that directional microphone hearing aids (DMHAs) are a
      viable means for improving the signal-to-noise ratio (SNR) for hearing-impaired
      listeners. The amount of directional advantage they provide, however, remains
      relatively unclear because of variability observed among individual studies. The
      present investigation was undertaken in an attempt to establish the degree of
      advantage provided by DMHAs. Data were synthesized from 72 and 74 experiments,
      respectively, on omnidirectional hearing aids and DMHAs representing both
      favorable and unfavorable outcomes. Using a meta-analytic approach, 138 weighted
      averages were derived for a variety of comparable independent and dependent
      variables. Comparisons were made for hearing-impaired and normal-hearing
      listeners. Findings are discussed with regard to their clinical and research
      implications.

PMID- 11332521
TI  - Newborn hearing screens may give a false sense of security.
AB  - Certain risk factors result in a higher incidence of delayed-onset hearing loss.
      Ten subjects who passed auditory brainstem response birth screenings and later
      returned with bilateral sensorineural hearing loss are examined in this report.
      Although not all subjects in this report had respiratory distress, this study
      reveals a high correlation between mechanical ventilation and delayed-onset
      hearing loss.

PMID- 11332522
TI  - Interleukin 1 signal transduction--current concepts and relevance to
      periodontitis.
AB  - This review examines a well-characterized factor, interleukin 1 (IL-1), that has
      recently received considerable attention. A level of understanding is emerging
      that goes beyond simple recognition that IL-1 plays a role in disease, and begins
      to explain the molecular mechanisms of function. This review summarizes some
      current information on the importance of IL-1 in periodontitis as well as the
      signal transduction of IL-1, from binding to its cell-surface receptors, to the
      activation of cytoplasmic mediators and transcription factors responsible for the
      induction of target genes. The effect of IL-1 signal transduction is ultimately
      the activation and repression of specific transcription factors that regulate
      genes responsible for cellular activities. As additional steps of signal
      transduction become better-characterized, these insights may facilitate the
      development of improved therapeutic approaches for controlling inflammation and
      connective tissue destruction in a variety of diseases.

PMID- 11332523
TI  - The relationship among dental status, nutrient intake, and nutritional status in
      older people.
AB  - Dental health status may influence nutrition. The objective of this part of the
      National Diet and Nutrition Survey was to assess if there is a relationship
      between dental status in people 65 years and older and intake of certain
      nutrients and any link between dental status and blood-derived values of key
      nutrients. Random national samples of independently living subjects and those
      living in institutions had dental examinations, interviews, four-day food
      diaries, and blood and urine analyzed. In the sample living independently,
      intakes of most nutrients were lower in edentate than dentate subjects. Intake of
      non-starch polysaccharides, protein, calcium, non-heme iron, niacin, and vitamin
      C was significantly lower in edentate subjects. People with 21 or more teeth
      consumed more of most nutrients, particularly of non-starch polysaccharide. This
      relationship in intake was not apparent in the hematological analysis. Plasma
      ascorbate and plasma retinol were the only analytes significantly associated with
      dental status.

PMID- 11332524
TI  - Hyper-excretion of human immunodeficiency virus type 1 RNA in saliva.
AB  - Anatomical compartments (e.g., the reproductive tract) are reservoirs of human
      immunodeficiency virus type-1 (HIV-1) and potential sites of residual infection
      in patients receiving anti-retroviral therapy (ART). Viral hyper-excretion
      relative to blood is a hallmark of reservoirs. To determine whether hyper
      excretion can occur in the oral cavity, we compared viral loads in blood plasma
      and saliva of 67 adults. Salivary viral hyperexcretion was defined as a four-fold
      or higher viral load in saliva than in plasma. HIV-1 RNA was detected in 79% of
      plasma samples, in 44% of unfiltered saliva samples, in 16% of filtered saliva
      samples, and in 59% of saliva-derived cell pellets. Compared with non-hyper
      excretors (n = 62), hyper-excretors (n = 5) had elevated levels of viral RNA in
      unfiltered saliva and saliva-derived cells, HIV-associated periodontal disease,
      gingival inflammation, and no combination ART. Morphological characterization of
      cell pellets identified lymphocytes as a likely HIV-1 source. These collective
      findings are consistent with an oral HIV-1 reservoir in selected individuals.

PMID- 11332525
TI  - Move of adults with mental retardation from institutions to community-based
      living: changes in the oral microbiological flora.
AB  - In the Western world, the policy of deinstitutionalization and integration of
      individuals with mental retardation is generally accepted. We tested the
      hypothesis that de-institutionalization may lead to changes of habits with a
      potential to influence oral health. When 57 adults with mental retardation moved
      from an institution to community-based living, their oral hygiene habits,
      gingival bleeding, and a three-day food record were registered one month before
      and 9 and 21 months after the move. Mutans streptococci and lactobacilli in
      saliva, P. intermedia/P. nigrescens, P. gingivalis, and A. actinomycetemcomitans
      in supragingival plaque, and C. albicans on mucous membranes were analyzed. After
      21 months of community-based living, fewer persons showed high classes of mutans
      streptococci, growth of P. intermedia/P. nigrescens, and high frequency of
      sucrose intake, and more subjects showed growth of C. albicans. In a short
      perspective, the indicators of oral diseases suggest an unchanged or lower risk
      of oral diseases after the de-institutionalization of individuals with moderate
      or severe mental retardation.

PMID- 11332526
TI  - A re-analysis of a caries clinical trial by survival analysis.
AB  - The decline in caries prevalence, the increases in the level of fluoride
      exposure, and the lack of placebo control subjects have complicated caries
      clinical trials in recent times. There has been a substantial increase in the
      numbers of subjects required for the detection of statistically significant
      differences between dental products, and hence, the cost of these trials has
      grown enormously. This study uses a new statistical approach to the analysis of
      the data from these trials with the ultimate aim of providing a more sensitive
      method of analysis. The new approach uses survival analysis, where the outcome
      measure is the survival time of an individual tooth surface. It exploits recent
      developments in the analysis of clustered survival data where survival times
      within the same cluster or subject are correlated. To illustrate, the new method
      of analysis was used for the North Wales, UK, caries clinical trial. It is
      concluded that survival analysis uses most of the data available in a caries
      clinical trial, an outcome measure that is easily understood and may lead to a
      more sensitive method of analysis.

PMID- 11332527
TI  - Occlusal stability in shortened dental arches.
AB  - Shortened dental arches consisting of anterior and premolar teeth have been shown
      to meet oral functional demands. However, the occlusal stability may be at risk
      as a result of tooth migration. The aim of this nine-year study was to
      investigate occlusal stability in shortened dental arches as a function over
      time. Occlusal stability indicators were: 'interdental spacing', 'occlusal
      contacts of anterior teeth in Intercuspal Position', 'overbite', 'occlusal tooth
      wear', and 'alveolar bone support'. Subjects with shortened dental arches (n =
      74) were compared with subjects with complete dental arches (controls, n = 72).
      Repeated-measurement regression analyses were applied to assess age-dependent
      variables in the controls and to relate the occlusal changes to the period of
      time since the treatment that led to the shortened dental arches. Compared with
      complete dental arches, shortened dental arches had similar overbite and occlusal
      tooth wear. They showed more interdental spacing in the premolar regions, more
      anterior teeth in occlusal contact, and lower alveolar bone scores. Since the
      differences remained constant over time, we conclude that shortened dental arches
      can provide long-term occlusal stability. Occlusal changes were self-limiting,
      indicating a new occlusal equilibrium.

PMID- 11332528
TI  - Motion of the human mandibular condyle during mastication.
AB  - It has been reported that loading to the mandible during closing movement makes
      the condylar path move more in the superior direction than that during the free
      closing movement. In this study, the hypothesis was tested that the displacement
      of the condyle on the chewing side is greater in the direction of the mandibular
      fossa than that on the non-chewing side. Using a six-degrees-of-freedom jaw
      movement recording system, we recorded condylar motion in 12 healthy adults
      without TMD, during the chewing of a large hard gummy jelly. The maximum
      displacements at the condyle on the chewing side from the maximum intercuspation
      (CO) position were significantly larger in the superior and medial directions at
      the initial stage and in the posterior direction at all stages (0.5 mm, 0.5 mm,
      and 0.6 mm, respectively) than those on the non-chewing side (0.0 mm, 0.1 mm, and
      0.1 mm, respectively). This suggests that, in healthy adults, the condyles at CO
      are located in a position such that excessive load is not applied to the
      temporomandibular joint when there are the aforementioned displacements.

PMID- 11332529
TI  - Rhythmic masticatory muscle activity during sleep in humans.
AB  - Rhythmic Masticatory Muscle Activity (RMMA) is frequently observed during sleep
      in normal subjects and sleep bruxers. We hypothesized that some normal subjects
      exhibit RMMA at a lower frequency than sleep bruxers. Polysomnographic data from
      82 normal subjects were compared with data from 33 sleep bruxers. RMMA episodes
      were defined as three or more consecutive bursts of masseter EMG activity, with
      or without tooth-grinding. Such episodes were observed in nearly 60% of normal
      subjects. A lower frequency of episodes was noted in normal subjects than in
      bruxers. Sleep organization was similar between groups. Bruxers had twice as many
      masseter muscle bursts per episode and episodes of higher amplitude compared with
      controls with RMMA. The high prevalence of RMMA observed in normal subjects
      suggests that this activity is related to certain sleep-related physiological
      functions, including autonomic activation.

PMID- 11332530
TI  - Accuracy of Kubelka-Munk reflectance theory applied to human dentin and enamel.
AB  - The Kubelka-Munk (K-M) theory provides a reflectance model for translucent
      materials placed on backings of different colors. We hypothesize that Kubelka
      Munk (K-M) theoretical diffuse reflectance spectra of dentin and enamel are in
      good agreement with observed diffuse reflectance. The aim of this study was to
      measure the reflectance of enamel and dentin specimens and to compare the
      measured values of reflectance with K-M theoretical values. Disc-shaped specimens
      of enamel, dentin, and enamel/dentin were prepared from extracted teeth. Diffuse
      reflectance spectra were measured on three backings by means of a reflectance
      spectrophotometer over every wavelength (lambda) from 400 to 700 nm at three
      thicknesses. The measured reflectance values were fit by non-linear regression to
      corrected K-M theory. The low value of the reported errors associated with the
      application of K-M theory illustrated that the theoretical diffuse reflectance
      spectra of dentin and enamel are in good agreement with the observed diffuse
      reflectance.

PMID- 11332531
TI  - Anisotropy of tensile strength of root dentin.
AB  - An effect of dentinal tubule orientation on mechanical properties of dentin has
      been difficult to demonstrate. We have tested the hypothesis that ultimate
      tensile strength (UTS) of dentin is affected by tubule (and hence collagen
      fibril) orientation. The UTS of human root dentin was investigated by direct
      tensile and diametral testing of specimens of known orientation prepared from
      extracted teeth. Dumbbell-shaped samples were machined for direct tensile testing
      (load parallel or perpendicular to tubule direction) and cylinders for diametral
      testing (load at 0 degrees, 45 degrees, 67.5 degrees, and 90 degrees). Fractured
      surfaces were examined by SEM. UTS was lowest when the tensile force was parallel
      to tubule orientation, and greatest at 90 degrees to tubule orientation (fracture
      parallel to tubule direction). SEM views of fractured surfaces suggested that
      microstructure contributes to fracture patterns. At least for properties
      involving disruption of the collagen matrix, root dentin shows a definite
      anisotropy.

PMID- 11332532
TI  - Intermittent force in orthodontic tooth movement.
AB  - A single orthodontic activation lasting one hour can initiate tooth movement. The
      purpose of this study is to examine tooth movement, osteoclasts, and root
      resorption in rats following several one-hour activations. Rats (n = 144) were
      randomly assigned to intermittent (multiple activations of 1 hr/day), continuous,
      and sham appliances. Twelve rats were killed at 3, 5, 7, and 14 days. Tooth
      movement, osteoclasts, osteoclast %, and root resorption % were quantified.
      Continuous force moved molars mesially at days 3 and 14 (p < 0.05), but
      intermittent and sham did not. Intermittent and continuous force increased
      osteoclast numbers at days 3, 5, and 7 (p < 0.05). Continuous force increased
      osteoclast surface on days 3 and 14 (p < 0.05). Continuous force increased root
      resorption at days 5, 7, and 14 (p < 0.05). These results demonstrate that
      orthodontic force for one hour in 24 stimulates osteoclasts at compression sites
      but does not stimulate tooth movement or root resorption.

PMID- 11332533
TI  - Mechanical stimulation induces CTGF expression in rat osteocytes.
AB  - Connective tissue growth factor (CTGF), which is encoded by an immediate early
      gene and a member of the CCN family, has been shown to be expressed in
      osteoblasts, fibroblasts, and chondrocytes. Although CTGF is expressed in bone
      and cartilage tissues, we tested the hypothesis that CTGF is regulated in
      mechanotransduction. In the alveolar bone during experimental tooth movement,
      CTGF mRNA was expressed in osteoblasts and in osteocytes localized around the
      periodontal ligament under control conditions. Interestingly, 12 hrs after the
      start of experimental tooth movement, the expression of CTGF mRNA in osteocytes
      and osteoblasts became more intense around the periodontal ligament, and the
      intense expression of CTGF extended to osteocytes situated deep in alveolar bone
      matrix apart from periodontal ligament in both tension and compression sides. Our
      present findings indicate that CTGF could play a role in regulation of osteocyte
      function during the mechanical stimulation of bone.

PMID- 11332534
TI  - Glucosyltransferase inactivation reduces dental caries.
AB  - Dental caries has been an intractable disease in spite of intense dental
      research. The metabolic acids produced by mutans streptococci demineralize the
      tooth surface and lead to dental caries. The enzyme glucosyltransferase (GTF)
      produced by mutans streptococci is the key factor in this process. Oral bacterial
      GTFs use sucrose as a substrate in synthesis of either water-soluble or insoluble
      glucans. In this investigation, kinetic studies with divalent metal ions revealed
      their strong binding affinity to GTF. The metal ions also proved to be strong
      inhibitors of the enzyme. Here we describe a simple method of inactivating the
      enzyme that actively participates in dental caries by taking advantage of a
      Fenton reaction which requires metal ions such as iron or copper and peroxide.
      The hydroxyl radical ions produced via the Fenton reaction inactivate GTF, a
      factor in the production of dental caries.

PMID- 11332535
TI  - Evidence for reactive nitrogen species formation in the gingivomucosal tissue.
AB  - An increase in nitric oxide production has been demonstrated in periodontitis.
      Here we investigated the potential role of nitric-oxide-derived nitrating species
      (such as peroxynitrite) in a rat model of ligature-induced periodontitis.
      Formation of 3-nitrotyrosine, the stable product formed from tyrosine reacting
      with nitric-oxide-derived nitrating species, was detected in the gingivomucosal
      tissue. 3-Nitrotyrosine immunohistochemical analysis revealed a significant
      elevation in the number of immunopositive leukocytes, and higher immunoreactivity
      of the gingival ligaments and epithelium in the ligated than in the contralateral
      (control) side. On both sides, several 3-nitrotyrosine-positive bands and, on the
      ligated side, a unique 52-kDa 3-nitrotyrosine-positive band were detected by
      Western blot. However, in the sterile gingivomucosal tissue of rat pups, no 3
      nitrotyrosine or inducible nitric oxide synthase immunoreactivity was found.
      Analysis of these data suggests that resident bacteria of the gingivomucosal
      tissue induce an increase in reactive nitrogen species, which is greatly enhanced
      by plaque formation in periodontitis.

PMID- 11332536
TI  - Immunohistochemical evidence for ATP receptors in human dental pulp.
AB  - Evidence is accumulating which supports a role for ATP in the initiation of pain
      by acting on P2X receptors, in particular P2X3, expressed on nociceptive afferent
      nerve terminals. To investigate whether this receptor plays a role in dental
      pain, we studied the presence and distribution of P2X3 receptors in human dental
      pulp, and their co-localization with other neural markers. Pulps were removed
      from extracted third molars and immunohistochemically stained with an antibody
      against P2X3 receptors. P2X3 immunoreactive (-ir) nerve fibers were detected in
      the main body of the pulp, in the sub-odontoblastic plexus of Raschkow, and
      within the odontoblastic area. Co-localization of the P2X3-ir neurons with
      neurofilament protein (NF) showed that the majority of the fibers were positive
      for both NF and P2X3. Double labeling with isolectin B4 (IB4) showed that all
      P2X3-ir neurons also bind IB4. We conclude that P2X3 receptors are present on
      both myelinated and unmyelinated nerve fibers in human dental pulp and may play a
      role in dental pain mechanisms.

PMID- 11332537
TI  - Differences in parasympathetic vasodilator and salivary responses in the cat
      submandibular gland between lingual and chorda-lingual nerve stimulation.
AB  - Experimental activation of parasympathetic vasodilatation and salivation in the
      submandibular gland by a "pseudoreflex" method has definite advantages over other
      commonly used methods. However, it is unclear which stimulation sites allow for
      avoidance of direct activation of the parasympathetic efferents to this gland. We
      examined this question in heavily anesthetized (alpha-chloralose and urethane),
      artificially ventilated, cervically vago-sympathectomized cats, using the
      intersection of the chorda-lingual nerve and the submandibular gland duct ("the
      intersection") as our reference point. Both vasodilatation and salivation evoked
      by electrical stimulation of the lingual nerve were abolished by section of the
      chorda-lingual nerve (10 mm proximal to the intersection), provided the
      stimulation site was distal to the intersection by 4 mm or more. This salivation
      was abolished by the muscarinic receptor antagonist, scopolamine. Thus, by
      careful choice of stimulation site, submandibular gland responses mediated solely
      by reflex parasympathetic mechanisms can be evoked by lingual nerve stimulation
      in this preparation.

PMID- 11332538
TI  - Multi-stage model estimates of lung cancer risk from exposure to diesel exhaust,
      based on a U.S. railroad worker cohort.
AB  - A California Environmental Protection Agency (Cal/EPA) report concluded that a
      reasonable and likely explanation for the increased lung cancer rates in numerous
      epidemiological studies is a causal association between diesel exhaust exposure
      and lung cancer. A version of the present analysis, based on a retrospective
      study of a U.S. railroad worker cohort, provided the Cal/EPA report with some of
      its estimates of lung cancer risk associated with diesel exhaust. The individual
      data for that cohort study furnish information on age, employment, and mortality
      for 56,000 workers over 22 years. Related studies provide information on exposure
      concentrations. Other analyses of the original cohort data reported finding no
      relation between measures of diesel exhaust and lung cancer mortality, while a
      Health Effects Institute report found the data unsuitable for quantitative risk
      assessment. None of those three works used multistage models, which this article
      uses in finding a likely quantitative, positive relations between lung cancer and
      diesel exhaust. A seven-stage model that has the last or next-to-last stage
      sensitive to diesel exhaust provides best estimates of increase in annual
      mortality rate due to each unit of concentration, for bracketing assumptions on
      exposure. Using relative increases of risk and multiplying by the background lung
      cancer mortality rates for California, the 95% upper confidence limit of the 70
      year unit risks for lung cancer is estimated to be in the range 2.1 x 10(-4)
      (microg/m3)(-1) to 5.5 x 10(-4) (microg/m3)(-1). These risks constitute the low
      end of those in the Cal/EPA report and are below those reported by previous
      investigators whose estimates were positive using human data.

PMID- 11332539
TI  - Limits of applicability for the deterministic approximation of the two-step
      clonal expansion model.
AB  - Motivated by a hypothesis published recently, the limits of applicability of the
      deterministic approximation of the two-step clonal expansion model are
      investigated. The approximate hazard increases unlimited, while the exact hazard
      is approaching a constant value. The approximate solution becomes inapplicable
      for hazards in the order of that constant rate. When the initiation rate is much
      larger than the cell division rate, the survival rate is small when the
      approximation becomes inapplicable. The simplicity of the exact solutions
      suggests using them in all situations.

PMID- 11332540
TI  - A randomization test-based method for risk assessment in neurotoxicology.
AB  - A current trend in risk assessment for systemic toxicity (noncancer) endpoints is
      to utilize the observable range of the dose-effect curve in order to estimate the
      likelihood of obtaining effects at lower concentrations. Methods to accomplish
      this endeavor are typically based on variability in either the effects of fixed
      doses (benchmark approaches), or on variability in the doses producing a fixed
      effect (probabilistic or tolerance-distribution approaches). The latter method
      may be particularly desirable because it can be used to determine variability in
      the effect of an agent in a population, which is an important goal of risk
      assessment. This method of analysis, however, has typically been accomplished
      using dose-effect data from individual subjects, which can be impractical in
      toxicology. A new method is therefore presented that can use traditional groups
      design data to generate a set of dose-effect functions. Population tolerances for
      a specific effect can then be estimated from these model dose-effect functions.
      It is based on the randomization test, which assesses the generality of a data
      set by comparing it to a data set constructed from randomized combinations of
      single point estimates. The present article describes an iterative line-fitting
      program that generates such a data set and then uses it to provide risk
      assessments for two pesticides, triadimefon and carbaryl. The effects of these
      pesticides were studied on the locomotor activity of laboratory rats, a common
      neurobehavioral end point. Triadimefon produced dose-dependent increases in
      activity, while carbaryl produced dose-dependent decreases in activity. Risk
      figures derived from the empirical distribution of individual dose-effect
      functions were compared to those from the iterative line-fitting program. The
      results indicate that the method generates comparable risk figures, although
      potential limitations are also described.

PMID- 11332541
TI  - A health risk benchmark for the neurologic effects of styrene: comparison with
      NOAEL/LOAEL approach.
AB  - Benchmark dose (BMD) analysis was used to estimate an inhalation benchmark
      concentration for styrene neurotoxicity. Quantal data on neuropsychologic test
      results from styrene-exposed workers [Mutti et al. (1984). American Journal of
      Industrial Medicine, 5, 275-286] were used to quantify neurotoxicity, defined as
      the percent of tested workers who responded abnormally to > or = 1, > or = 2, or
      > or = 3 out of a battery of eight tests. Exposure was based on previously
      published results on mean urinary mandelic- and phenylglyoxylic acid levels in
      the workers, converted to air styrene levels (15, 44, 74, or 115 ppm). Nonstyrene
      exposed workers from the same region served as a control group. Maximum
      likelihood estimates (MLEs) and BMDs at 5 and 10% response levels of the exposed
      population were obtained from log-normal analysis of the quantal data. The
      highest MLE was 9 ppm (BMD = 4 ppm) styrene and represents abnormal responses to
      > or = 3 tests by 10% of the exposed population. The most health-protective MLE
      was 2 ppm styrene (BMD = 0.3 ppm) and represents abnormal responses to > or = 1
      test by 5% of the exposed population. A no observed adverse effect level/lowest
      observed adverse effect level (NOAEL/LOAEL) analysis of the same quantal data
      showed workers in all styrene exposure groups responded abnormally to > or = 1, >
      or = 2, or > or = 3 tests, compared to controls, and the LOAEL was 15 ppm. A
      comparison of the BMD and NOAEL/LOAEL analyses suggests that at air styrene
      levels below the LOAEL, a segment of the worker population may be adversely
      affected. The benchmark approach will be useful for styrene noncancer risk
      assessment purposes by providing a more accurate estimate of potential risk that
      should, in turn, help to reduce the uncertainty that is a common problem in
      setting exposure levels.

PMID- 11332542
TI  - A risk management procedure for the Washington state ferries.
AB  - The state of Washington operates the largest passenger vessel ferry system in the
      United States. In part due to the introduction of high-speed ferries, the state
      of Washington established an independent blue-ribbon panel to assess the adequacy
      of requirements for passenger and crew safety aboard the Washington state
      ferries. On July 9, 1998, the Blue Ribbon Panel on Washington State Ferry Safety
      engaged a consultant team from The George Washington University and Rensselaer
      Polytechnic Institute/Le Moyne College to assess the adequacy of passenger and
      crew safety in the Washington state ferry (WSF) system, to evaluate the level of
      risk present in the WSF system, and to develop recommendations for prioritized
      risk reduction measures, which, once implemented, can improve the level of safety
      in the WSF system. The probability of ferry collisions in the WSF system was
      assessed using a dynamic simulation methodology that extends the scope of
      available data with expert judgment. The potential consequences of collisions
      were modeled in order to determine the requirements for onboard and external
      emergency response procedures and equipment. The methodology was used to evaluate
      potential risk reduction measures and to make detailed risk management
      recommendations to the blue-ribbon panel and the Washington State Transportation
      Commission.

PMID- 11332543
TI  - Safety risk analysis of an innovative environmental technology.
AB  - The authors describe a decision and risk analysis performed for the cleanup of a
      large Department of Energy mixed-waste subsurface disposal area governed by the
      Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA).
      In a previous study, the authors worked with the site decision makers, state
      regulators, and U.S. Environmental Protection Agency regional regulators to
      develop a CERCLA-based multiobjective decision analysis value model and used the
      model to perform a screening analysis of 28 remedial alternatives. The analysis
      results identified an innovative technology, in situ vitrification, with high
      effectiveness versus cost. Since this technology had not been used on this scale
      before, the major uncertainties were contaminant migration and pressure buildup.
      Pressure buildup was a safety concern due to the potential risks to worker
      safety. With the help of environmental technology experts remedial alternative
      changes were identified to mitigate the concerns about contaminant migration and
      pressure buildup. The analysis results showed that the probability of an event
      with a risk to worker safety had been significantly reduced. Based on these
      results, site decision makers have refocused their test program to examine in
      situ vitrification and have continued the use of the CERCLA-based decision
      analysis methodology to analyze remedial alternatives.

PMID- 11332544
TI  - Fault tree analysis for exposure to refrigerants used for automotive air
      conditioning in the United States.
AB  - A fault tree analysis was used to estimate the number of refrigerant exposures of
      automotive service technicians and vehicle occupants in the United States.
      Exposures of service technicians can occur when service equipment or automotive
      air-conditioning systems leak during servicing. The number of refrigerant
      exposures of service technicians was estimated to be 135,000 per year. Exposures
      of vehicle occupants can occur when refrigerant enters passenger compartments due
      to sudden leaks in air-conditioning systems, leaks following servicing, or leaks
      caused by collisions. The total number of exposures of vehicle occupants was
      estimated to be 3,600 per year. The largest number of exposures of vehicle
      occupants was estimated for leaks caused by collisions, and the second largest
      number of exposures was estimated for leaks following servicing. Estimates used
      in the fault tree analysis were based on a survey of automotive air-conditioning
      service shops, the best available data from the literature, and the engineering
      judgement of the authors and expert reviewers from the Society of Automotive
      Engineers Interior Climate Control Standards Committee. Exposure concentrations
      and durations were estimated and compared with toxicity data for refrigerants
      currently used in automotive air conditioners. Uncertainty was high for the
      estimated numbers of exposures, exposure concentrations, and exposure durations.
      Uncertainty could be reduced in the future by conducting more extensive surveys,
      measurements of refrigerant concentrations, and exposure monitoring.
      Nevertheless, the analysis indicated that the risk of exposure of service
      technicians and vehicle occupants is significant, and it is recommended that no
      refrigerant that is substantially more toxic than currently available substitutes
      be accepted for use in vehicle air-conditioning systems, absent a means of
      mitigating exposure.

PMID- 11332546
TI  - Organizational theory and the stages of risk communication.
AB  - The evolution of risk communication has been described as a series of
      communication strategies. This article suggests that organizational theory
      provides another dimension to understanding the evolution of risk communication,
      and that risk communication can be seen as an organizational adaptation of
      chemical manufacturers to external pressure. Following the tragedy in Bhopal the
      chemical manufacturing sector's loss of legitimacy led to destabilization of its
      authority and to increased uncertainty in its external environment. Risk
      communication was one means to increase legitimacy, thereby decreasing
      uncertainty and potential impact on resources. However, although risk
      communication may evolve from crises of legitimacy, the concept of "isomorphism"-
      conformance to norms within a corporate sector--predicts this need not be the
      case.

PMID- 11332545
TI  - Risk perception and experience: hazard personality profiles and individual
      differences.
AB  - The dominance of the "psychometric" paradigm and the consequent emphasis on
      personality profiles of hazards has resulted in little attention being given to
      individual variability in risk judgments. This study examines how far differences
      in experience of risk activities can explain individual variability in risk
      assessments. A questionnaire study (n = 172) was used to explore the
      relationships between experience and risk perceptions in relation to 16 risk
      activities. It was expected that these relationships would differ for voluntary
      and involuntary activities. Measures of experience included assessments of
      "impact" and "outcome" valence as well as "frequency." These three aspects of
      experience each related to risk assessment but their relationship depended on
      whether the risk experiences were voluntary or not. The results indicate the
      importance of developing more fine-grained ways of indexing risk experience.

PMID- 11332547
TI  - Limits of knowledge and the limited importance of trust.
AB  - Perceived risk and related attitudes have been implicated as major factors in
      many of the difficult policy problems that face modern society (nuclear power,
      genetically modified food, etc). Experts often argue that no or very small risks
      are involved; people are still worried. Why? The standard answer is lack of
      trust. Data on trust and risk perception, however, point to only a weak
      relationship between the two (r approximately 0.3). It is suggested here that the
      reason for the surprisingly minor importance of trust is that people believe that
      there are clear limits to how much science and experts know. Results are
      presented from studies of risk perception of the public, experts, and
      politicians. Politicians and members of the public believe that there are many
      unknown effects of technology and such beliefs were strongly related to their
      perceived risk. Experts on nuclear waste, on the other hand, seemed to believe
      that little is unknown in their field of expertise. Regression analyses of risk
      perception showed the unknown-effects factor to be a more important explanatory
      factor than trust for the public and politicians.

PMID- 11332548
TI  - Modeling lung cancer risk from diesel exhaust: suitability of the railroad worker
      cohort for quantitative risk assessment.

PMID- 11332549
TI  - Better negative than positive? Evidence of a bias for negative information about
      possible health dangers.
AB  - Do the results of a scientific study influence confidence in the study's validity
      and the magnitude of change in the resulting perceived danger of the health risk
      investigated? Findings from the three investigations reported here indicate that
      scientific results that confirm a danger (negative results) do affect confidence
      in a study's validity and resulting risk assessments differently than results
      indicating low risk (positive results). Findings of Study 1 revealed that
      research results indicating a health risk were more trusted than results
      indicating little health risk. This effect was independent of the credibility of
      the information source. Study 2 demonstrated that confidence in research results
      increased with an increasing indication of health risk. Study 3 showed that
      people have more confidence in the results of animal tests on a food additive
      indicating negative human health effects than in animal tests indicating that a
      food additive is harmless. The findings have important practical implications.
      The observed asymmetry between positive and negative research results may be one
      reason that people are afraid of many of the hazards they are faced with in
      modern society.

PMID- 11332550
TI  - Chronic health risks from aggregate exposures to ionizing radiation and
      chemicals: scientific basis for an assessment framework.
AB  - Very little quantitative analysis is currently available on the cumulative
      effects of exposure to multiple hazardous agents that have either similar or
      different mechanisms of action. Over the past several years, efforts have been
      made to develop the methodologies for risk assessment of chemical mixtures, but
      mixed exposures to two or more dissimilar agents such as radiation and one or
      more chemical agents have not yet been addressed in any substantive way. This
      article reviews the current understanding of the health risks arising from mixed
      exposures to ionizing radiation and specific chemicals. Specifically discussed is
      how mixed radiation/chemical exposures, when evaluated in aggregation, were
      linked to chronic health endpoints such as cancer and intermediate health
      outcomes such as chromosomal aberrations. Also considered is the extent to which
      the current practices are consistent with the scientific understanding of the
      health risks associated with mixed-agent exposures. From this the discussion
      moves to the research needs for assessing the cumulative health risks from
      aggregate exposures to ionizing radiation and chemicals. The evaluation indicates
      that essentially no guidance has been provided for conducting risk assessment for
      two agents with different mechanisms of action (i.e., energy deposition from
      ionizing radiation versus DNA interactions with chemicals) but similar biological
      endpoints (i.e., chromosomal aberrations, mutations, and cancer). The literature
      review also reveals the problems caused by the absence of both the basic science
      and an appropriate evaluation framework for the combined effects of mixed-agent
      exposures. This makes it difficult to determine whether there is truly no
      interaction or somehow the interaction is masked by the scale of effect
      observation or inappropriate dose-response assumptions.

PMID- 11332551
TI  - Practical methods for meeting remediation goals at hazardous waste sites.
AB  - Risk-based cleanup goals or preliminary remediation goals (PRGs) are established
      at hazardous waste sites when contaminant concentrations in air, soil, surface
      water, or groundwater exceed specified acceptable risk levels. When derived in
      accordance with the Environmental Protection Agency's risk assessment guidance,
      the PRG is intended to represent the average contaminant concentration within an
      exposure unit area that is left on the site following remediation. The PRG,
      however, frequently has been used inconsistently at Superfund sites with a number
      of remediation decisions using the PRG as a not-to-exceed concentration (NTEC).
      Such misapplications could result in overly conservative and unnecessarily costly
      remedial actions. The PRG should be applied in remedial actions in the same
      manner in which it was generated. Statistical methods, such as Bower's Confidence
      Response Goal, and mathematical methods such as "iterative removal of hot spots,"
      are available to assist in the development of NTECs that ensure the average
      postremediation contaminant concentration is at or below the PRG. These NTECs can
      provide the risk manager with a more practical cleanup goal. In addition, an
      acute PRG can be developed to ensure that contaminant concentrations left on-site
      following remediation are not so high as to pose an acute or short-term health
      risk if excessive exposure to small areas of the site should occur. A case study
      demonstrates cost savings of five to ten times associated with the more
      scientifically sound use of the PRG as a postremediation site average, and
      development of a separate NTEC and acute PRG based on the methods referenced in
      this article.

PMID- 11332552
TI  - Evaluation of the physical hazards associated with two remedial alternatives at a
      Superfund site.
AB  - This study presents an evaluation of the risks due to the physical hazards
      associated with two remedial alternatives for a former chemical manufacturing
      facility in New Jersey. Both the on-site and off-site risk of work-related
      fatalities during remedy implementation and the risks of accident or accident
      related fatalities during the off-site transport of site-related materials were
      evaluated. The two remedial alternatives evaluated were on-site containment and
      excavation with off-site incineration. The risk of at least one fatality due to a
      work-related accident was estimated for on-site activities associated with each
      remedial alternative, and for off-site incineration. The risks of at least one
      accident and of one accident-related fatality were calculated with accident and
      fatality data from the U.S. Department of Transportation. In addition, the risk
      of at least one accident that might potentially affect a natural resource (e.g.,
      river, lake, or national park) was evaluated. This evaluation indicates that the
      risk of a work-related fatality is over an order of magnitude higher, and the
      risk of an accident or accident-related fatality is over three orders of
      magnitude higher, for the excavation/off-site incineration remedial alternative
      than for the on-site containment alternative. Overall, this study indicates that
      the physical hazards associated with excavation and off-site incineration are
      much greater than those associated with on-site containment for this site.
      Therefore, if a choice between the two remedial alternatives were to be made
      based solely on physical hazards and accident risk, the on-site containment
      alternative would be more protective of human health and the environment than the
      excavation/off-site incineration alternative.

PMID- 11332553
TI  - Estimation of error and bias in Bayesian Monte Carlo decision analysis using the
      bootstrap.
AB  - Bayesian Monte Carlo (BMC) decision analysis adopts a sampling procedure to
      estimate likelihoods and distributions of outcomes, and then uses that
      information to calculate the expected performance of alternative strategies, the
      value of information, and the value of including uncertainty. These decision
      analysis outputs are therefore subject to sample error. The standard error of
      each estimate and its bias, if any, can be estimated by the bootstrap procedure.
      The bootstrap operates by resampling (with replacement) from the original BMC
      sample, and redoing the decision analysis. Repeating this procedure yields a
      distribution of decision analysis outputs. The bootstrap approach to estimating
      the effect of sample error upon BMC analysis is illustrated with a simple value
      of-information calculation along with an analysis of a proposed control structure
      for Lake Erie. The examples show that the outputs of BMC decision analysis can
      have high levels of sample error and bias.

PMID- 11332554
TI  - Disparity in quantitative risk assessment: a review of input distributions.
AB  - Monte Carlo simulations are commonplace in quantitative risk assessments (QRAs).
      Designed to propagate the variability and uncertainty associated with each
      individual exposure input parameter in a quantitative risk assessment, Monte
      Carlo methods statistically combine the individual parameter distributions to
      yield a single, overall distribution. Critical to such an assessment is the
      representativeness of each individual input distribution. The authors performed a
      literature review to collect and compare the distributions used in published QRAs
      for the parameters of body weight, food consumption, soil ingestion rates,
      breathing rates, and fluid intake. To provide a basis for comparison, all
      estimated exposure parameter distributions were evaluated with respect to four
      properties: consistency, accuracy, precision, and specificity. The results varied
      depending on the exposure parameter. Even where extensive, well-collected data
      exist, investigators used a variety of different distributional shapes to
      approximate these data. Where such data do not exist, investigators have
      collected their own data, often leading to substantial disparity in parameter
      estimates and subsequent choice of distribution. The present findings indicate
      that more attention must be paid to the data underlying these distributional
      choices. More emphasis should be placed on sensitivity analyses, quantifying the
      impact of assumptions, and on discussion of sources of variation as part of the
      presentation of any risk assessment results. If such practices and disclosures
      are followed, it is believed that Monte Carlo simulations can greatly enhance the
      accuracy and appropriateness of specific risk assessments. Without such
      disclosures, researchers will be increasing the size of the risk assessment
      "black box," a concern already raised by many critics of more traditional risk
      assessments.

PMID- 11332555
TI  - Characterizing dose-response relationships in multiple cancer bioassays.
AB  - In the evaluation of chemical compounds for carcinogenic risk, regulatory
      agencies such as the U.S. Environmental Protection Agency and National Toxicology
      Program (NTP) have traditionally fit a dose-response model to data from rodent
      bioassays, and then used the fitted model to estimate a Virtually Safe Dose or
      the dose corresponding to a very small increase (usually 10(-6)) in risk over
      background. Much recent interest has been directed at incorporating additional
      scientific information regarding the properties of the specific chemical under
      investigation into the risk assessment process, including biological mechanisms
      of cancer induction, metabolic pathways, and chemical structure and activity.
      Despite the fact that regulatory agencies are currently poised to allow use of
      nonlinear dose-response models based on the concept of an underlying threshold
      for nongenotoxic chemicals, there have been few attempts to investigate the
      overall relationship between the shape of dose-response curves and mutagenicity.
      Using data from an historical database of NTP cancer bioassays, the authors
      conducted a repeated-measures Analysis of the estimated shape from fitting
      extended Weibull dose-response curves. It was concluded that genotoxic chemicals
      have dose-response curves that are closer to linear than those for nongenotoxic
      chemicals, though on average, both types of compounds have dose-response curves
      that are convex and the effect of genotoxicity is small.

PMID- 11332556
TI  - Electrogram polarity and cavotricuspid isthmus block during ablation of typical
      atrial flutter.
AB  - INTRODUCTION: The atrial activation sequence around the tricuspid annulus has
      been used to assess whether complete block has been achieved across the
      cavotricuspid isthmus during radiofrequency ablation of typical atrial flutter.
      However, sometimes the atrial activation sequence does not clearly establish the
      presence or absence of complete block. The purpose of this study was to determine
      whether a change in the polarity of atrial electrograms recorded near the
      ablation line is an accurate indicator of complete isthmus block. METHODS AND
      RESULTS: Radiofrequency ablation was performed in 34 men and 10 women (age 60 +/-
      13 years [mean +/- SD]) with isthmus-dependent, counterclockwise atrial flutter.
      Electrograms were recorded around the tricuspid annulus using a duodecapolar halo
      catheter. Electrograms recorded from two distal electrode pairs (E1 and E2)
      positioned just anterior to the ablation line were analyzed during atrial flutter
      and during coronary sinus pacing, before and after ablation. Complete isthmus
      block was verified by the presence of widely split double electrograms along the
      entire ablation line. Complete bidirectional isthmus block was achieved in 39
      (89%) of 44 patients. Before ablation, the initial polarity of E1 and E2 was
      predominantly negative during atrial flutter and predominantly positive during
      coronary sinus pacing. During incomplete isthmus block, the electrogram polarity
      became reversed either only at E2, or at neither E1 nor E2. In every patient, the
      polarity of E1 and E2 became negative during coronary sinus pacing only after
      complete isthmus block was achieved. In 4 patients (10%), the atrial activation
      sequence recorded with the halo catheter was consistent with complete isthmus
      block, but the presence of incomplete block was accurately detected by inspection
      of the polarity of E1 and E2. CONCLUSION: Reversal of polarity in bipolar
      electrograms recorded just anterior to the line of isthmus block during coronary
      sinus pacing after ablation of atrial flutter is a simple, quick, and accurate
      indicator of complete isthmus block.

PMID- 11332557
TI  - Assessment of complete isthmus block after ablation of typical atrial flutter:
      can we rely on a single criterion?

PMID- 11332558
TI  - Provoked and spontaneous high-frequency, low-amplitude, respirophasic noise
      transients in patients with implantable cardioverter defibrillators.
AB  - INTRODUCTION: Ventricular oversensing (OS) of respirophasic noise transients may
      cause spurious detections and therapies and pacing inhibition among patients with
      implantable cardioverter defibrillators (ICDs). The incidence of OS and its
      relationship to clinical variables and ICD system design are unknown. METHODS AND
      RESULTS: Three hundred twenty-nine patients performed provocative respiratory
      maneuvers at rest during intrinsic rhythm and continuous ventricular pacing. OS
      resulting in spurious ventricular detections was provoked in 3 (0.9%) of 329
      patients during intrinsic rhythm and 34 (10.3%) of 329 during pacing. Noise
      transients not recognized and marked as sensed events, but visually evident on
      the local endocardial ventricular electrogram, were provoked in an additional 23
      (7.0%) of 329 patients. Multivariate logistic regression identified history of
      spontaneous OS (P < 0.0005, odds ratio 9.7, 95% confidence interval [CI] 1.9 to
      50.0), automatic gain control device (P < 0.0005, odds ratio 5.3, 95% CI 2.6 to
      10.8) or integrated bipolar lead (P = 0.05, odds ratio 2.6, 95% CI 1.0 to 7.25),
      and male gender (P = 0.008, odds ratio 3.7, 95% CI 1.2 to 11.1) as predictive of
      provocable OS. Spontaneous OS resulting in spurious ventricular detections and
      therapies occurred in 12 (3.6%) patients during follow-up. Eleven of 12
      spontaneous episodes occurred in male patients during ventricular pacing; 11 of
      12 patients had automatic gain control devices and integrated bipolar leads.
      CONCLUSION: OS is commonly provoked in ICD patients during ventricular pacing and
      may occur spontaneously, causing spurious tachyarrhythmia therapies and pacing
      inhibition. Differences in the incidence of spontaneous and provoked OS between
      ICD systems can be explained on the basis of unique features of automatic sensing
      systems and sensing lead design.

PMID- 11332559
TI  - Problems of heart rate correction in assessment of drug-induced QT interval
      prolongation.
AB  - INTRODUCTION: Estimation of QT interval prolongation belongs to safety assessment
      of every drug. Among unresolved issues, heart rate correction of the QT interval
      may be problematic. This article proposes a strategy for heart rate correction in
      drug safety studies and demonstrates the strategy using a study of ebastine, a
      nonsedating antihistamine. METHODS AND RESULTS: Four-way cross-over Phase I study
      investigated 32 subjects on placebo, ebastine 60 mg once a day, 100 mg once a
      day, and terfenadine 180 mg twice a day. Repeated ECGs were obtained before each
      arm and after 7 days of treatment. The changes in heart rate-corrected QTc
      interval were investigated using (A) 20 published heart rate correction formulas,
      (B) a correction formula optimized by QT/RR regression modeling in all baseline
      data, and (C) individual corrections optimized for each subject by drug-free
      QT/RR regression modeling. (A) Previously published correction formulas found QTc
      interval increases on terfenadine. The results with ebastine were inconsistent.
      For instance, Bazett's and Lecocq's correction found significant QTc increase and
      decrease on ebastine, respectively. The results were related (absolute value(r) >
      0.95) to the success of each formula (independence of drug-free QTc and RR
      intervals). (B) The pooled drug-free QT/RR regression found an optimized
      correction QTc = QT/RR(0.314). QTc interval changes on placebo, ebastine 60 mg,
      ebastine 100 mg, and terfenadine were -1.95 +/- 6.87 msec (P = 0.18), -3.91 +/-
      9.38 msec (P = 0.053), 0.75 +/- 8.23 msec (P = 0.66), and 12.95 +/- 14.64 msec (P
      = 0.00025), respectively. (C) Individual QT/RR regressions were significantly
      different between subjects and found optimized corrections QTc = QT/RR(alpha)
      with alpha = 0.161 to 0.417. Individualized QTc interval changes on placebo,
      ebastine 60 mg, ebastine 100 mg, and terfenadine were -2.76 +/- 5.51 msec (P =
      0.022), -3.15 +/- 9.17 msec (P = 0.11), -2.61 +/- 9.55 msec (P = 0.19), and 12.43
      +/- 15.25 msec (P = 0.00057, respectively. Drug-unrelated QTc changes up to 4.70
      +/- 8.92 msec reflected measurement variability. CONCLUSION: Use of published
      heart rate correction formulas in the assessment of drug-induced QTc prolongation
      is inappropriate, especially when the drug might induce heart rate changes.
      Correction formulas optimized for pooled drug-free data are inferior to the
      formulas individualized for each subject. Measurement imprecision and natural
      variability can lead to mean QTc interval changes of 4 to 5 msec in the absence
      of drug treatment.

PMID- 11332560
TI  - Making QT correction simple is complicated.

PMID- 11332561
TI  - T wave alternans threshold in normal children.
AB  - INTRODUCTION: Sustained microvolt-level T wave alternans (TWA) during exercise is
      a predictor of ventricular arrhythmia propensity in adult populations. TWA occurs
      in normal adults, but it is rare at < 70% of predicted maximum heart rate. An
      onset heart rate < or = 110 is believed to be significant. The aim of this study
      was to examine the feasibility of performing the test in children and to
      determine the normal heart rate threshold for sustained TWA in children. METHODS
      AND RESULTS: Alternans was evaluated during bicycle exercise in 100 normal
      volunteers aged 8 to 17 years. Adequate resting data were obtained in 76 of 100
      children and was negative in all. Exercise data from 16 of 100 was excluded due
      to excessive noise. Median maximum heart rate was 192 (range 140 to 214).
      Sustained alternans was absent in 75 (89%) of 84. In the nine children with
      sustained alternans, median onset heart rate was 138 (range 120 to 158), and 7 of
      9 had an onset heart rate > or = 135. Median heart rate threshold as a percentage
      of predicted maximum heart rate (220 - age) was 67% (range 58% to 76%). Only 1
      subject (1.2%) had an onset heart rate < 60% of predicted maximum. There was no
      significant difference between age, gender, endurance, maximum heart rate, QRS
      duration, QT interval, or QTc in those with and those without sustained TWA.
      CONCLUSION: Noninvasive assessment of TWA is feasible at > or = 8 years of age.
      Sustained TWA was present in 11% of normal children, but was absent at heart
      rates below 120 and rare (1.2%) below 60% of predicted maximum heart rate.

PMID- 11332562
TI  - T wave alternans: from cell to clinical.

PMID- 11332563
TI  - Diagnosis of amiodarone pulmonary toxicity with high-resolution computerized
      tomographic scan.
AB  - INTRODUCTION: Amiodarone pulmonary toxicity is a serious adverse effect that can
      be fatal. The diagnosis is difficult due to the nonspecificity of symptoms,
      clinical findings, and test results. Because of its high iodine content,
      amiodarone deposition can be detected by sensitive high-resolution computed
      tomographic (CT) scan techniques. We hypothesized that pulmonary toxicity can be
      diagnosed more readily when these scans indicate the presence of increased
      attenuation of either pleural or pulmonary densities representing high iodine
      amiodarone deposits. METHODS AND RESULTS: This case control study included 16
      patients taking chronic amiodarone. Eight cases presented with severe respiratory
      and other symptoms and were matched with 8 controls, 4 with mild or chronic
      respiratory symptoms. All patients underwent high-resolution CT of the chest. All
      cases had positive CT scan results demonstrating bilateral air-space disease,
      parenchymal bands, and thickened septal and bronchiolitis obliterans. All
      minimally or asymptomatic patients had negative scans with no area of high
      attenuation. All cases had > or = 1 lesion with high-attenuation density. The
      cases were treated successfully by supportive care, discontinuation of
      amiodarone, and, rarely, corticosteroid therapy. Two cases had delayed diagnosis
      of amiodarone pulmonary toxicity and were managed successfully only after CT.
      CONCLUSION: High-resolution CT may be a valuable noninvasive test to aid in the
      diagnosis of amiodarone pulmonary toxicity in symptomatic patients.

PMID- 11332564
TI  - Amiodarone pulmonary toxicity and Professor Hounsfield.

PMID- 11332565
TI  - Catheter cryoablation of the atrioventricular node in patients with atrial
      fibrillation: a novel technology for ablation of cardiac arrhythmias.
AB  - INTRODUCTION: Recent animal studies demonstrated the feasibility and safety of
      applying percutaneous catheter cryoablation technology for ablation of
      arrhythmogenic sites. The studies also showed that reversible "ice mapping" can
      be performed before creating permanent lesions. We investigated the feasibility
      and safety of applying this new technology in man. METHODS AND RESULTS:
      Cryoablation of the AV node (AVN) using a 9-French quadripolar catheter with a 4
      mm electrode tip was attempted in 12 patients (mean age 67.8 +/- 11.4 years) with
      refractory atrial fibrillation. Whereas technical issues prevented adequate
      tissue contact in two patients, complete AVN block was obtained in the remaining
      10 patients after 4.8 +/- 1.9 cryoapplications lasting 5.5 +/- 0.2 minutes
      resulting in temperatures of -58.1 degrees +/- 5.4 degrees C. In all patients
      with sinus rhythm at the time of the procedure, cryomapping at warmer
      temperatures induced reversible AVN block and allowed confirmation of a
      successful site before definitive ablation. Intracardiac echocardiography was
      performed in three patients and allowed visualization of the cryocatheter
      endocardial contact and cryolesion formation. No major procedural complications
      were reported. After 6 months of follow-up, 8 of 10 initially successful patients
      remained in complete block; 1 had partial recovery of AVN conduction manifested
      by atrial fibrillation with a slow ventricular response, and 1 fully recovered
      AVN conduction. CONCLUSION: (1) Catheter cryoablation of the AVN can be performed
      safely in man. (2) Reversible cryomapping is feasible and may offer an advantage
      over radiofrequency ablation. (3) Cryocatheter-endocardial contact and cryolesion
      growth can be monitored with intracardiac echocardiography.

PMID- 11332566
TI  - Ventricular fibrillation sensing and detection by implantable defibrillators: is
      one better than the others? A prospective, comparative study.
AB  - INTRODUCTION: We prospectively compared the performance of the sensing and
      detection systems of three leading defibrillator manufacturers: Medtronic,
      Guidant, and Ventritex. METHODS AND RESULTS: Ventricular fibrillation signal was
      digitally recorded during defibrillator implantation and subsequently played back
      sequentially to a Medtronic Micro Jewel II 7223Cx, a Guidant MINI II 1762, and a
      Ventritex Cadet V-115C. The devices were programmed for single-zone detection, at
      nominal settings. Rate cutoff was set at 320 msec (185/min for the MINI). We
      analyzed 253 episodes from 47 patients. Median undersensing was 0%, 2.1%, and
      5.3% for the Jewel, MINI, and Cadet, respectively (P < 0.001 for each paired
      comparison). Detection time was 4.1 +/- 1.6 seconds, 3.4 +/- 1.6 seconds, and 4.3
      +/- 2.2 seconds for the Jewel, MINI, and Cadet, respectively (P < 0.001 between
      MINI-Jewel and MINI-Cadet; P < 0.01 between Jewel-Cadet). Delayed detection
      (detection time longer than the mean of all observations + 2 SD) occurred in 3
      (1.2%), 7 (2.8%), and 18 (7.1%) episodes for the Jewel, MINI, and Cadet,
      respectively. Performance for all devices was worse when the short-separation
      integrated bipolar lead was used and when the episode followed a failed high
      energy shock. CONCLUSION: Statistically significant differences were seen in
      sensing and detection performance among the devices and device/lead combinations
      during ventricular fibrillation. These differences are related to specific
      features of the respective devices and should be taken into account during
      clinical practice, as well as in future device development.

PMID- 11332567
TI  - Modern implantable cardioverter defibrillators: are some more equal than others?

PMID- 11332568
TI  - Electrocardiographic prediction of abnormal genotype in congenital long QT
      syndrome: experience in 101 related family members.
AB  - INTRODUCTION: Previous studies showed that diagnosing congenital long QT syndrome
      (LQTS) is difficult due to variable penetrance and genetic heterogeneity,
      especially when subjects from multiple families with diverse mutations are
      combined. We hypothesized that a combination of clinical and ECG techniques could
      identify gene carriers within a single family with congenital LQTS. METHODS AND
      RESULTS: One hundred one genotyped members of a family with LQTS, including 26
      carriers of a HERG mutation, underwent history and ECG analysis. Forty-eight
      family members also underwent exercise testing with QT and T wave alternans (TWA)
      analysis and 24-hour Holter monitoring with QT and heart rate variability
      analysis. A logistic regression model, which included age, gender, QTc, and QTc
      by age, provided the best prediction of gene carrier status, although there was
      substantial overlap (78%) of QTc among subjects with and without the mutation.
      QTc was not helpful as a discriminator in children < or = 13 years. TWA (observed
      infrequently) did not add significantly to the model's ability to predict
      abnormal genotype. CONCLUSION: Even in this homogeneous LQTS population, the
      phenotype was so variable that clinical and detailed ECG analyses did not permit
      an accurate diagnosis of gene carrier status, especially in children. Sustained
      microvolt TWA was a specific (100%) but insensitive (18%) marker for LQTS. Its
      ability to predict risk of arrhythmia in this population remains to be
      determined. Genetic testing serves an essential role in screening for carriers of
      LQTS.

PMID- 11332569
TI  - Long QT syndrome: more questions.

PMID- 11332570
TI  - Reduction in atrial defibrillation threshold by a single linear ablation lesion.
AB  - INTRODUCTION: This study investigated a hybrid approach to reduce the atrial
      defibrillation threshold (ADFT) by determining the effect of a single linear
      radiofrequency ablation (RFA) lesion on both the ADFT and activation patterns
      during atrial fibrillation (AF). METHODS AND RESULTS: In 18 open chest sheep (45
      to 57 kg), coil defibrillation electrodes were placed in a superior vena
      cava/right ventricular configuration. AF was induced by burst pacing and
      maintained with acetyl beta-methylcholine (2 to 42 microL/min). ADFTs were
      obtained before and after a linear RFA lesion was created in the left atrium
      (LAL; n = 6), right atrium (RAL; n = 6), or neither atrium as a control (n = 6).
      In animals receiving an LAL, a 504-unipolar-electrode plaque was sutured to the
      LA. For animals receiving an RAL, two 504-electrode plaques were placed, one each
      on the LA and RA. From each plaque, activations were recorded before and after
      ADFT shocks, and organizational characteristics of activations were analyzed
      using algorithms that track individual wavefronts. In sham-treated controls, the
      ADFT did not change. In contrast, LAL reduced ADFT energy 29%, from 4.5 +/- 2.3 J
      to 3.2 +/- 2.0 J (P < 0.05). RAL reduced ADFT energy 25%, from 2.0 +/- 0.9 J to
      1.5 +/- 0.7 J (P < 0.05). AF activation was substantially more organized after
      RFA than before RFA for both the RAL- and LAL-treated animals. CONCLUSION: A
      single RFA lesion in either the RA or LA reduces the ADFT in this sheep model.
      This decrease is associated with an increase in fibrillatory organization.

PMID- 11332571
TI  - Chromanol 293B inhibits slowly activating delayed rectifier and transient outward
      currents in canine left ventricular myocytes.
AB  - INTRODUCTION: Drugs that selectively inhibit the slowly activating component of
      the delayed rectifier potassium current (I(Ks)) are being considered as possible
      antiarrhythmic agents, because they produce more prolongation of action potential
      duration at fast rates with less transmural dispersion of repolarization compared
      with blockers of the rapidly activating component (I(Kr)). Although the chromanol
      derivative chromanol 293B has been shown to be relatively selective in blocking
      I(Ks) in some species, its selectivity is far from established. METHODS AND
      RESULTS: The present study uses whole-cell, patch-clamp technique to examine the
      selectivity of this compound for inhibition of I(Ks) in comparison with other
      repolarizing ionic currents, such as I(Kr), inward rectifier potassium current
      (I(Kl)), transient outward current (I(to)), and L-type calcium current (I(Ca-L))
      in canine left ventricular mid-myocardial and endocardial cells. Chromanol 293B
      blocked I(Ks) with an IC50 of 1.8 microM and I(to) with an IC50 of 38 microM.
      Concentrations as high as 30 microM did not affect I(Kl), I(Kr), or I(Ca-L).
      Higher concentrations of chromanol 293B (100 microM) caused a slight, but
      statistically insignificant, inhibition of I(Kr). CONCLUSION: Our results
      indicate that chromanol 293B is a relatively selective blocker of I(Ks) in canine
      left ventricular myocytes.

PMID- 11332572
TI  - Properties and substrate of slow pathway exposed with a compact node targeted
      fast pathway ablation in rabbit atrioventricular node.
AB  - INTRODUCTION: The properties and substrates of slow and fast AV nodal pathway
      remain unclear. This applies particularly to the slow pathway (SP), which is
      largely concealed by fast pathway (FP) conduction. We designed a new FP ablation
      approach that exposes the SP over the entire cycle length range and allows for
      its independent characterization and ablation. METHODS AND RESULTS: Premature
      stimulation was performed before and after FP ablation with 5.4 +/- 1.9 lesions
      (300-microm diameter each; overall lesion size 1.4 +/- 0.5 mm) targeting the
      junction between perinodal and compact node tissues in seven rabbit heart
      preparations. The resulting SP recovery curve and control curve had the same
      maximum nodal conduction time (165 +/- 22 msec vs 164 +/- 24 msec; P = NS) and
      effective refractory period (101 +/- 10 msec vs 100 +/- 9 msec; P = NS). The two
      curves covered the same cycle length range. However, the SP curve was shifted up
      with respect to control one at intermediate and long cycle lengths and thus
      showed a longer minimum nodal conduction time (81 +/- 15 msec vs 66 +/- 10 msec;
      P < 0.01) and functional refractory period (180 +/- 11 msec vs 170 +/- 12 msec; P
      < 0.05). The SP curve was continuous and closely fitted by a single exponential
      function. Small local lesions (2 +/- 1) applied to the posterior nodal extension
      resulted in third-degree nodal block in all preparations. CONCLUSION: The
      posterior nodal extension can sustain effective atrial-His conduction at all
      cycle lengths and account for both the manifest and concealed portion of SP. Slow
      and FP conduction primarily arise from the posterior extension and compact node,
      respectively.

PMID- 11332573
TI  - Nondiscrete functional pathways and asymmetric transitional zone: a new concept
      for AV nodal electrophysiology.

PMID- 11332574
TI  - Decremental atriofascicular accessory pathway with bidirectional conduction:
      delineation of atrial and ventricular insertion by radiofrequency current
      application.
AB  - A 17-year-old girl with a corrected complex congenital heart disease and
      recurrent episodes of supraventricular tachycardia was referred for catheter
      ablation. Electrophysiologic studies revealed the presence of an accessory
      pathway (AP) with bidirectional conduction and decremental properties. We
      demonstrated a course parallel to the node-His AV conduction system. Transient
      abolition of the bidirectional conduction through the AP was obtained by
      radiofrequency application to the ventricular insertion located in the distal
      right bundle branch and to the atrial insertion, located in the mid-anterior
      atrial septum. Radiofrequency application at the low anterior atrial septum,
      above the His bundle, successfully abolished AP conduction without affecting AV
      nodal conduction. Demonstration of the course and insertions of the AP, its
      bidirectional decremental conduction properties, and the association with a
      complex congenital heart disease are exceptional and interesting findings and
      raise the possibility of an accessory AV node with a parallel conduction pathway
      to the right bundle branch.

PMID- 11332575
TI  - Intravenous administration of class I antiarrhythmic drugs induced T wave
      alternans in a patient with Brugada syndrome.
AB  - A 71-year-old man who experienced aborted sudden death was referred to our
      hospital. Coronary artery disease and cerebral accident were ruled out by
      conventional tests. The 12-lead ECG obtained at rest showed a right bundle branch
      block pattern and ST segment elevation in leads V1 to V3. Double ventricular
      extrastimuli at coupling intervals >180 msec induced ventricular fibrillation
      (VF) twice during electrophysiologic study. Intravenous administration of
      procainamide accentuated ST segment elevation in leads V1 to V3, and visible T
      wave alternans was induced in leads V2 and V3 at a dose of 450 mg. Initiation of
      T wave alternans was not associated with changes of the cardiac cycle or
      development of premature beats. When procainamide infusion was discontinued, T
      wave alternans disappeared before the elevated ST segment returned to the control
      level. Pilsicainide also accentuated ST segment elevation and induced similar T
      wave alternans in leads V2 and V3. Class I antiarrhythmic drug-related T wave
      alternans has been reported rarely in Brugada syndrome, but it may represent
      enhanced arrhythmogenicity of VF. We need to monitor closely and study the
      clinical implications of T wave alternans in Brugada syndrome.

PMID- 11332576
TI  - Arrhythmogenesis in heart failure.
AB  - In a rabbit model of heart failure produced by combined pressure and volume
      overload, nonsustained ventricular tachycardias developed in 15 of 23 failing
      rabbits. Sinus rate was increased in rabbits dying suddenly, but was decreased in
      survivors. This also was true in isolated preparations. Microelectrode recordings
      from ventricular trabeculae both from patients with end-stage failure and from
      failing rabbits showed that in half of the preparations, delayed
      afterdepolarizations and triggered activity occurred, but only in the presence of
      norepinephrine and a lowered extracellular K+ concentration of 3 mM. This was due
      to spontaneous release of Ca2+ from the sarcoplasmic reticulum.

PMID- 11332577
TI  - Another role for the sympathetic nervous system in the long QT syndrome?

PMID- 11332578
TI  - 2:1 tracking of sinus rhythm in a patient with a dual-chamber implantable
      cardioverter defibrillator: what is the mechanism?

PMID- 11332579
TI  - Pulmonary vein dissection during mapping of atrial fibrillation.

PMID- 11332580
TI  - Transfer of refrozen twice-thawed embryos do not decrease the implantation rate.
AB  - PURPOSE: To assess the ability of twice frozen/thawed multi-cell embryos to
      implant in the human uterus. METHOD: Fourteen frozen embryo transfer (ET) cycles,
      in which at least one twice-frozen embryo was thawed for transfer, were matched
      to frozen ET cycles in which no twice-frozen embryos were thawed. The number of
      embryos thawed at the pronuclear stage and at the multi-cell stage were matched.
      RESULTS: Multi-cell embryos frozen once had a 76.3% survival rate after thaw and
      those frozen twice had a 74.0% survival rate. For frozen ET cycles that had no
      twice-frozen embryos, the viable pregnancy and implantation rates were 58.3% and
      29.8%, respectively. The corresponding rates for cycles involving at least one
      twice-frozen embryo were 50.0% and 25.5%, respectively. CONCLUSION: The inclusion
      of twice-frozen embryos in the embryo pool did not reduce the implantation rate.

PMID- 11332581
TI  - The clinical significance of antenatal pathological Doppler findings in the fetal
      middle cerebral artery in cases with peripheral reduced diastolic doppler flow
      but no absence of end-diastolic flow in the umbilical artery or fetal aorta.
AB  - PURPOSE: The effects of antepartum pathological Doppler findings in the fetal
      middle cerebral artery in cases with simultaneously peripheral reduced diastolic
      Doppler flow on perinatal outcome and the odds ratio of perinatal risks were
      studied. METHODS: 214 patients were examined by color Doppler ultrasound in
      relationship to complications in gestation and labor and fetal outcome. One
      thousand and seventy Doppler flow measurements of the middle cerebral artery, the
      umbilical artery and the fetal aorta between 28 and 40 weeks of gestation were
      performed. Sensitivity and odds ratio of synchronous cerebral pathological and
      peripheral pathological Doppler blood flow with regard to the prediction of
      intrauterine growth retardation, rate of cesarean section, preterm delivery and
      newborn depression was calculated. In all Doppler measurements there were no
      cases with absence of end-diastolic flow. RESULTS: Preterm delivery rate and
      intrauterine growth retardation rate were significantly higher in cases of
      synchronous cerebral pathological and peripheral pathological Doppler blood flow
      as in cases of isolated reduced peripheral blood flow (p<0.001; odds ratio 13.2
      and 16.6). CONCLUSION: Pregnancies with no absence of end-diastolic flow in the
      fetal aorta or umbilical artery, but with reduced diastolic flow in these vessels
      and simultaneous pathological Doppler findings in the fetal middle cerebral
      artery are high risk pregnancies, above all in respect to intrauterine growth
      retardation, preterm delivery and newborn depression. Surveillance of pregnant
      women should be performed in a perinatal centre.

PMID- 11332582
TI  - Effects of herbal medicines on menopausal symptoms induced by gonadotropin
      releasing hormone agonist therapy.
AB  - The therapeutic effects of certain Japanese herbal medicines on menopausal
      symptoms induced by gonadotropin-releasing hormone agonist therapy were examined
      in Japanese women with endometriosis, adenomyosis, or leiomyoma. Menopausal
      symptoms occurred in 17 of the 22 patients. Toki-shakuyaku-san, Shakuyaku-kanzo
      to, Keishi-bukuryo-gan, Kami-shoyo-san, Tokaku-joki-to, or Keishi-to was
      administered to 13 of the 17 patients with menopausal symptoms, and efficacy was
      observed in all 13. Eleven patients with hot flashes were treated with Toki
      shakuyaku-san, and all II patients experienced some relief; four experienced
      total relief. Three patients complaining of severe shoulder stiffness were
      treated with Shakuyaku-kanzo-to and were completely relieved of symptoms. There
      was no significant change in serum estradiol levels after treatment with the
      Japanese herbal medicines. Our results indicate that Japanese herbal medicines
      can be recommended for menopausal symptoms induced by gonadotropin-releasing
      hormone agonists without a negative effect on serum estradiol levels.

PMID- 11332583
TI  - Successful diagnostic and surgical hysteroscopy for endometrial ossification.
AB  - PURPOSE OF INVESTIGATION: Diagnostic-operative hysteroscopy was successful in two
      cases of endometrial ossification, and fertility was restored. METHODS: A 30-year
      old and a 32-year-old woman presented at our Department with a history of
      secondary infertility, complaining of pelvic pain, dysmenorrhea and polymenorrhea
      which lasted for about one year before admission. Previous ultrasound studies
      revealed the presence of two bright hyperechogenic bands with posterior
      shadowing. RESULTS: In both cases diagnostic-operative hysteroscopies were
      performed, displaying osseous fragments which were removed with resectoscopy,
      mainly mechanically. CONCLUSION: Hysteroscopic resection should be the elective
      treatment for endometrial ossification because it allows complete removal of
      osseous fragments and reduces the chance of residual synechia. The mean objective
      of hysteroscopy in endometrial ossification is the restitution of conceivement
      capability.

PMID- 11332584
TI  - Ultrastructural aspects of the postmenopausal endometrium after oral or
      transdermal estrogen administration.
AB  - In this report we examined the ultrastructural features of the postmenopausal
      endometrial cells of women treated with different doses of conjugated equine
      estrogen (CEE), or transdermal 17beta-estradiol. Eight women with uterine
      prolapse and at least 5 years of menopause were randomly divided into four groups
      and treated as follows: (I) no hormonal treatment; (II) 0.625mg/day of CEE
      orally; (III) 1.25mg/day of CEE orally; (IV) 50microg/day of 17beta-estradiol
      transdermally. Hormones were administered for 28 days followed by vaginal
      hysterectomy. Fragments of the endometrium were prepared for transmission
      electron microscopic analysis. We observed that the postmenopausal endometrium of
      the untreated group was atrophic with lined superficial epithelial cuboidal
      cells. The presence of gland and stroma cells with clear cytoplasm containing few
      organelles and heterochromatin nuclei were also observed. On the contrary, the
      endometrium of the group that received 0.625mg/day of CEE showed signs of
      proliferative cells such as the presence of numerous organelles in the cytoplasm
      and euchromatic nuclei. All of the proliferative effects on the endometrium were
      more pronounced in the groups that received 1.25mg/day of CEE and 50microg/day of
      transdermal 17beta-estradiol. We concluded that the ultrastructural proliferative
      changes of the postmenopausal endometrium induced by 1.25mg/day of CEE were
      similar to 50microg/day of transdermal 17beta-estradiol.

PMID- 11332585
TI  - Prenatal management of inherited urogenital malformation: case report.
AB  - Documentation of unique kidney renal function early in pregnancy can be helpful
      in defining prenatal management and therefore in improving prognosis. Antenatal
      diagnosis of a solitary kidney was performed at 20 weeks' gestation in a foetus
      with a 1,7 chromosome translocation. Because of the decreasing renal function and
      the increasing pelvic dilatation, an early in utero stenting was placed at 23
      weeks' gestation. Optimal outcome occurred and the baby was delivered at 32
      weeks. Complete assessment of the malformation showed a left hydronephrosis due
      to a megaureter, right renal agenesis with ipsilateral cryprorchidism and
      agenesis of the right vas deferens. The chromosomic translocation was inherited
      from the mother who was affected by uterus didelphys, obstructed right hemivagina
      and right renal agenesis. Renal function of the unique kidney with hydronephrosis
      can be early diagnosed and promptly treated. This condition should also increase
      the index of suspicion of underlying genital and chromosomal anomalies.

PMID- 11332586
TI  - Doppler velocimetry and non stress test in severe fetal growth restriction.
AB  - OBJECTIVE: The aim of our study was to evaluate the efficacy of Doppler
      velocimetry and cardiotocography in surveillance of the fetus affected by severe
      fetal growth retardation (FGR) and hence their capacity in predicting adverse
      perinatal outcome. This could therefore permit the timing of delivery thus
      reducing perinatal morbidity and mortality. METHODS: 53 women with high risk
      pregnancies, all suffering from various pathologies such as gestational
      hypertension, preeclampsia, HELLP syndrome, Antithrombin III deficit, and in whom
      FGR (fetal abdominal circumference < 2.5th percentile for gestational age)
      diagnosed between the 24th and 35th week of gestational age, were retrospectively
      enrolled in the study. Doppler velocimetry was carried out on the main vascular
      districts - both arterial [umbilical artery (UA), middle cerebral artery (MCA),
      aorta (Ao) and uterine artery] and venous [umbilical vein (UV), ductus venosus
      (DV), inferior vena cava (IVC)]. Also evaluated was the amniotic fluid index
      (AFI). Daily non stress tests (NST) were conducted at least thrice a day for an
      overall period of not shorter than 60 min. Also considered were the methods of
      delivery and the perinatal outcome, e.g. gestational age at birth, perinatal
      mortality, incidence resuscitation, etc. RESULTS: The 53 patients studied were
      subdivided into three groups on the basis of the initial velocimetric exam of the
      umbilical and uterine arteries. Group A was comprised of those with altered
      waveforms of the UA, Group B those with altered waveforms on the uterine artery
      while Group C contained those with altered waveforms both of the UA and uterine
      artery. The period of study for group C was on average six days (p < 0.05) while
      for groups A and B they were on average 10 and 22 days, respectively. Group C
      also presented higher incidences of altered waveforms in the venous compartment,
      i.e. absent or reversed end diastole (ARDEF) was observed in 89% of the cases
      versus 0% and 7.6% observed in Group A and B, respectively. Altered waveforms in
      the DV and pulsations in the UV were both observed in Group C while the same was
      not observed in either group A or B. The NST did not show any substantial
      difference between the groups - only as the appearance of decelerations present
      in over half the cases in all groups at the end of the study. Group C also
      presented higher incidences in adverse perinatal outcome as compared to groups A
      and B such as as low birth weight (868 g vs 1,324 g & 1,397 g, p < 0.001),
      neonatal resuscitation (52.6% vs 0% & 7.6% p = 0.001), longer periods of
      admission to neonatal intensive care unit (67 days vs 32 & 33 p < 0.001) and
      perinatal mortality (36% vs 0 & 0, p < 0.05). The velocimetric indices which
      appear to better predict perinatal mortality are those related to the venous
      compartment giving a diagnostic accuracy of 92.8% (KI > 0.75) in case of
      pulsations in the UV, 86.6% (KI > 0.75) with alterations on the DV, and of 78.5%
      (KI > 0.40) for those on the IVC. Cardiotocography revealed to be less capable in
      predicting perinatal mortality giving a diagnostic accuracy of 66.6% (KI > 0.40)
      with a non reactive, non variable NST. CONCLUSION: The data presented show that
      velocimetric modifications in the fetal venous compartment constitute a relevant
      prognostic sign in the prediction of perinatal mortality and neonatal
      resuscitation. The further the vessels compromised are from the heart, the higher
      is the relative risk for perinatal mortality, equal to 5.0 (95% C.I. = 0.61-40.9)
      with alterations on the IVC, of 8.2 (95% CI = 1.04-61.5) when they involve the
      DV, and of 18.0 (95% = 2.44-133) when pulsations are obtained on the UV.

PMID- 11332587
TI  - Effect of human follicular fluid on sperm survival.
AB  - OBJECTIVE: To study the effect of follicular fluid (FF) on sperm survival.
      METHOD: Swim-up sperm suspensions obtained from 20 men with normal semen analysis
      were incubated with Ham's F-10 only and Ham's F-10 supplemented with 20% FF or
      20% serum. Sperm motility was recorded every 12 hours for 72 hours. RESULTS:
      Sperm motility was maintained in all media for 48 hours. However, significantly
      more sperm samples remained motile at 72 hours in medium supplemented with FF and
      serum as compared to Ham's F-10 only. CONCLUSION: FF has a positive effect on
      conserving sperm motility as a function of time.

PMID- 11332588
TI  - Influence of the hormonal status on somatic, psychopathological and mood symptoms
      in climacteric women.
AB  - OBJECTIVE: To evaluate the influence of hormonal status on somatic,
      psychopathological and mood symptoms in climacteric women. METHOD: 122
      postmenopausal women have been evaluated by the PISA-system and P.O.M.S. (Profile
      of Mood States) to evaluate somatic, psychopathological and mood symptoms in a 3
      intervention trial (perimenopausal women, postmenopausal women on replacement
      therapy, and postmenopausal women without any therapy). RESULT: We found no
      statistically significant difference among the three groups. A clear trend has
      however resulted: sex hormones seem to decrease the depressive mood,
      aggressiveness/anger and sexual dissatisfaction. CONCLUSION: Our results are
      inconclusive but they suggest that hormones influence some psychological and mood
      symptoms during the climacterium.

PMID- 11332589
TI  - A study report of 174 units of placental umbilical cord whole blood transfusion
      in 62 patients as a rich source of fetal hemoglobin supply in different
      indications of blood transfusion.
AB  - BACKGROUND: In the animal kingdom, even herbivorous animals swallow the placenta
      after the birth of the baby (for example, the cow). In the human system, we do
      not know about the proper utilization of the placenta and membranes although
      there are suggestions regarding this on the basis of research on placental
      umbilical cord blood stem cells as an alternative to bone marrow transplantation.
      In this present series of placental umbilical cord whole blood transfusions, we
      wanted to examine the safety aspect of other components of cord blood
      transfusion, e.g., fetal RBC, growth factors and cytokine filled plasma, etc., in
      different indications of blood transfusion, from the pediatric to the geriatric
      age group, in malignant and non-malignant disorders affecting our patients.
      METHODS: One hundred and seventy-four units of umbilical cord whole blood were
      collected aseptically from the umbilical vein after caesarean section in standard
      pediatric blood transfusion bags, after the removal of the baby from the
      operative field and after confirming the stable condition of the mother. The
      volume of cord blood varied from 50 ml to 140 ml with a mean of 86 ml+/-16 ml.
      RESULTS AND ANALYSIS: The cord blood was transfused immediately (within three
      days of collection) to 62 patients from nine years to 78 years of age, of whom 32
      were suffering from varying stages and grades of malignancy from 1 April 1999
      till date i.e., 11 Aug 2000, after obtaining adequate consent and following the
      precautions of standard blood transfusion protocol. The remaining 30 patients
      included patients suffering from thalassemia major, aplastic anemia, systemic
      lupus erythematosus, chronic renal failure, rheumatoid arthritis, ankylosing
      spondylitis and a geriatric group of patients with benign prostatic hypertrophy.
      All have tolerated the procedure without any immunological or non-immunological
      reactions. CONCLUSION: On the basis of our experience with 174 units of placental
      umbilical cord whole blood transfusion in malignant and non-malignant conditions
      (within three days of collection and preservation at 1-6 degrees C in a
      refrigerator), we are of the opinion that this is a safe transfusion protocol
      which takes advantage of the safety of nature's finest biological sieve, i.e.,
      the placenta, as an alternative to adult whole blood transfusion. It also has the
      advantage of a higher oxygen carrying capacity of fetal hemoglobin in addition to
      many growth factors and other cytokine filled cord blood plasma along with its
      hypoantigenicity.

PMID- 11332590
TI  - Global challenges of cervical cancer prevention.

PMID- 11332591
TI  - The importance of high resolution transvaginal sonography in early screening of
      fetal chromosomal pathology.
AB  - BACKGROUND: Continuous technological improvement made in the field of ultrasound
      applied to obstetric diagnostics (see tridimensional sonography) has contributed
      to a better and non-invasive early diagnosis of fetal malformations. METHODS: To
      evaluate the usefulness of ultrasound in detecting early chromosomal
      derangements, the authors carried out a high resolution transvaginal sonography
      (> 6.5 mHz), between the 10th and 14th week of gestational age, on 650 pregnant
      women at risk for congenital anomalies and afterwards they were subjected to
      early amniocentesis RESULTS: Sonographic fetal anomalies were seen in 61 cases
      (9.3%). The incidence of fetal anomalies in these cases was 52.5%. Trisomies and
      number of sexual chromosome anomalies were seen, especially, in the cases of
      cystic septated hygroma and fetal nuchal translucency > or = 3 mm which are the
      most frequent sonographic markers of chromosomopathies. CONCLUSIONS: Although
      further studies are necessary, these findings suggest the usefulness of high
      resolution transvaginal sonography for the early screening of chromosomopathies.

PMID- 11332592
TI  - Association between duration of neonatal hospital stay and morbidity in the first
      month of life.
AB  - The morbidity of 506 healthy full-term newborns was studied in the first month of
      life in relation to the time they stayed in the hospital. The average time for
      the newborns who were born by vaginal delivery was 73.3+/-11.7 hours, while for
      those who were born by cesarean section it was 135+31.5 hours. Thirty-seven
      newborns presented health problems during the neonatal period (7.3%) and only 2%
      needed hospital readmission. The commonest problem in the newborns we studied was
      jaundice which appeared from the fourth to sixth day of life. During the second
      fortnight the commonest problems were infections of the respiratory tract. From
      the results of our study it is obvious that only a small percentage of
      readmissions could have been avoided if the original stay in hospital had been
      prolonged.

PMID- 11332593
TI  - Teflonoma presenting as a cystourethrocele.
AB  - We report an unusual case of teflonoma which appeared three years after teflon
      injection and presented as cystourethrocele. The pathology confirmed the presence
      of a giant cell reaction compatible with a teflonoma.

PMID- 11332594
TI  - Morphologic and morphometric study of the breast parenchyma of rats in persistent
      estrus treated with tamoxifen and conjugated estrogens.
AB  - PURPOSE: To evaluate the morphological and morphometric alterations produced by
      tamoxifen and conjugated estrogens in the mammary epithelium of rats in
      persistent estrus. METHODS: 33 adult female rats with persistent estrus induced
      by 1.25 mg testosterone propionate were divided at random into three groups:
      group I (n=12), receiving only water and used as a control; group II (n=10),
      treated with 500 microg tamoxifen daily; group III (n= 11), treated with 30
      microg conjugated estrogens daily. The first abdominal-inguinal pair of breasts
      was extirpated and processed for morphological and morphometric study. Data were
      analyzed statistically by the Kruskal-Wallis rank analysis of variance (p<0.05).
      RESULTS: The morphological study revealed signs of epithelial atrophy and the
      morphometric study showed a significant reduction in mean number of ducts and
      alveoli in groups II (10.1 and 1.9, respectively) and III (11.1 and 3.5,
      respectively) compared to the control group 1 (25.0 and 6.6, respectively). There
      was no significant difference between groups II and III. CONCLUSIONS: The present
      results indicate that, at the doses and during the time of treatment used, both
      tamoxifen and conjugated estrogens induced atrophy of the mammary epithelium of
      rats in persistent estrus.

PMID- 11332595
TI  - Ovarian pregnancy: a case report.
AB  - We report a rare case of ovarian pregnancy occurring in a 34-year old woman after
      natural conception. The natural history, management, and outcome of this rare
      extrauterine pregnancy are described.

PMID- 11332596
TI  - Protein targeting.

PMID- 11332597
TI  - fMLP receptor stimulated activation of macrophage: its effect on killing of
      intracellular Leishmania donovani.
AB  - The fMLP receptor of peritoneal macrophages stimulated by fMLP grafted liposomes
      as ligand, was analysed and compared with respective controls for its ability to
      promote killing of intracellular Leishmania parasites. fMLP grafted liposomes
      show greater efficacy in killing intracellular L. donovani (MHOM/IN/1983/AG83)
      parasites in a time dependent manner than free fMLP. fMLP grafted liposomes also
      release more active oxygen intermediates and reactive nitrogen intermediates (O2
      , H2O2, NO) than free fMLP. The key enzymes PKC and PTK for the respiratory burst
      and nitric oxide generation were found to be important in this fMLP receptor
      mediated signaling process as the enzyme specific inhibitors viz. staurosporine,
      genistein and AG126 suppressed the leishmanicidal effect of fMLP grafted
      liposomes. The above findings suggest that the fMLP receptor of macrophages
      activates PKC and PTK mediated signalling that is responsible for the
      intracellular parasite killing.

PMID- 11332598
TI  - Effects of two highly monounsaturated oils on lipid composition and enzyme
      activities in rat jejunum.
AB  - The effects of two monounsaturated fatty acid (MUFA) oils, olive oil (OO) and
      high-oleic sunflower oil (HOSO), with high content in oleic acid but differing in
      their non-fatty acid fraction, on brush-border membrane (BBM) lipid composition
      and fluidity and on mucosal enzyme activities of rat jejunum were studied.
      Animals were given semipurified diet with linoleic acid to prevent essential
      fatty acid deficiency (control group) or semipurified diet containing 10% of
      either OO or HOSO for 12 weeks. There was a significant decrease in the content
      of jejunal BBM phospholipids together with an increase in the level of free
      cholesterol in both oil-fed rats, when compared to control group. Although the
      increase in the BBM free cholesterol level was not statistically significant in
      HOSO-fed rats, a significant decrease in the phospholipid/free cholesterol ratio
      was found in both OO and HOSO-fed animals compared to control group. Rat jejunal
      BBM had a high level of free fatty acids which was increased in BBM isolated from
      OO and HOSO-fed animals. There was no statistical significant difference in the
      phospholipid distribution between the control and the OO group. However, HOSO-fed
      animals showed the lowest level of phosphatidylethanolamine together with the
      highest phosphatidylcholine content and the phosphatidylcholine/sphingomyelin
      ratio. The fatty acid pattern of jejunal BBM lipids was modified according to the
      major fatty acids in the oils. There was a decrease in both stearic acid (18:0)
      and linoleic acid (18:2 n-6), together with an increase in oleic acid (18:1 n-9)
      in jenunal BBM isolated from both oil experimental groups. All these results were
      accompanied by a significant increase in the BBM fluidity (as assessed by steady
      state fluorescence polarization of diphenylhexatriene) isolated from oil-fed rat,
      when compared to control group. OO and HOSO-fed animals had the lowest activities
      of sucrase and maltase, while alkaline phosphatase activity only was decreased in
      HOSO-fed animals. The specific activity of maltase was not modified in any
      experimental rats. In summary, both MUFA oils induced similar effects on jejunal
      BBM lipid composition, fluidity, sucrase, maltase and lactase activities.
      Furthermore, HOSO intake resulted in a lowest alkaline phosphatase activity which
      was accompanied by changes in individual phospholipid composition. All these
      results suggest that effects of MUFA oils on jejunal BBM lipid composition and
      hydrolase activities are most likely due to the presence of high content of oleic
      acid rather than other components contained in the non-fatty acid of olive oil.

PMID- 11332599
TI  - Inhibition of the ecto-ATPdiphosphohydrolase of Schistosoma mansoni by
      thapsigargin.
AB  - ATPdiphosphohydrolases (ATPDases) are ubiquitous enzymes capable of hydrolyzing
      nucleoside di- and triphosphates. Although a number of possible physiological
      roles have been proposed for ATPDases, detailed studies on structure-function
      relationships have generally been hampered by the lack of specific inhibitors of
      these enzymes. We have previously characterized a Ca2+-activated ATPDase on the
      external surface of the tegument of Schistosoma mansoni, the etiologic agent of
      human schistosomiasis. In the present work, we have examined the effects of
      thapsigargin, a sesquiterpene lactone known as a high affinity inhibitor of sarco
      endoplasmic reticulum calcium transport (SERCA) ATPase, on ATPDase activity.
      Whereas other lactones tested had little or no inhibitory action, thapsigargin
      inhibited ATP hydrolysis by the ATPDase (K(i) approximately 20 microM).
      Interestingly, hydrolysis of ADP was not inhibited by thapsigargin. The lack of
      inhibition of ATPase activity by orthovanadate, a specific inhibitor of P-type
      ATPases, and the inhibition of the Mg2+-stimulated ATP hydrolysis by thapsigargin
      ruled out the possibility that the observed inhibition of the ATPDase by
      thapsigargin could be due to the presence of contaminating SERCA ATPases in our
      preparation. Kinetic analysis indicated that a single active site in the ATPDase
      is responsible for hydrolysis of both ATP and ADP. Thapsigargin caused changes in
      both Vmax and Km for ATP, indicating a mixed type of inhibition. Inhibition by
      thapsigargin was little or not affected by changes in free Ca2+ or Mg2+
      concentrations. These results suggest that interaction of thapsigargin with the
      S. mansoni ATPDase prevents binding of ATP or its hydrolysis at the active site,
      while ADP can still undergo catalysis.

PMID- 11332600
TI  - Spacer length dependence on the efficiency of dimeric anionic peptides in gene
      transfer by glycosylated polylysine/plasmid complexes.
AB  - Amphiphilic anionic peptides have been used to enhance the efficiency of
      transfection by helping plasmids to escape from endosomes to the cytosol. It has
      been shown that efficiency of an eicosamers containing five glutamyl residues
      (E5), can be considerably enhanced either by transforming it into a dimer or by
      adding a tripeptide WYG in a C-terminal position (E5WYG). The dimerization of the
      peptide E5WYG leads to a more efficient tool when the dimerization device
      includes the tripeptide WYG unit and a longer spacer arm made of Gly-betaAla
      betaAla residues, but to a 10-fold less efficient tool when the dimerization
      device includes a shorter spacer, a glycyl residue. Both dimers are taken up by
      the cells to a similar extent. Both dimers seem to be surrounded similarly as far
      as the environmental pH is concerned. In contrast, we found a correlation between
      the propensity of the peptides to adopt a helical structure at neutral pH and the
      gene transfer efficiency.

PMID- 11332601
TI  - Delivery to macrophages of interleukin 3 loaded in mouse erythrocytes.
AB  - Mouse carrier erythrocytes containing 125I-interleukin 3 have been prepared and
      treated with band 3 crosslinking reagents. The incorporation of interleukin 3 by
      hypotonic treatment into mouse erythrocytes reached levels of about 15% of the
      interleukin 3 added to the medium being predominantly present in the cytosolic
      fraction (73%). Uptake fell to about 7.4% when using the same conditions but
      omitting hypotonic shock. The interaction of band 3 crosslinked interleukin 3
      loaded erythrocytes with macrophages was also studied. A high level of
      incorporation of interleukin 3 into macrophages was observed either from band 3
      crosslinked, interleukin 3-loaded erythrocytes or from interleukin 3 loaded
      erythrocytes. The observations encourage the view that the system may be able to
      deliver and target cytokines and other growth factors to macrophages.

PMID- 11332602
TI  - Combined vitamins Bl2b and C induce the glutathione depletion and the death of
      epidermoid human larynx carcinoma cells HEp-2.
AB  - The combination of hydroxocobalamin (vitamin B12b) and ascorbic acid (vitamin C)
      can cause the death of tumor cells at the concentrations of the components at
      which they are nontoxic when administered separately. This cytotoxic action on
      epidermoid human larynx carcinoma cells HEp-2 in vitro is shown to be due to the
      hydrogen peroxide generated by the combination of vitamins B12b and C. The drop
      in the glutathione level preceding cell death was found to be the result of
      combined action of the vitamins. It is supposed that the induction of cell death
      by combined action of vitamins B12b and C is connected to the damage of the cell
      redox system.

PMID- 11332603
TI  - Efficient gene delivery using anionic liposome-complexed polyplexes (LPDII).
AB  - Synthetic gene transfer vectors based on polyplexes complexed to anionic
      liposomes (LPDII vectors) were characterized for their transfection efficiency in
      cultured mammalian cells. The effects of polycation to DNA ratio, lipid to DNA
      ratio, choice of polycation and lipid composition were systematically evaluated
      in human oral carcinoma KB cells, using a luciferase reporter gene. For LPDII
      formulations containing poly-L-lysine and
      dioeoylphosphatidylethanolamine/cholesteryl hemisuccinate (DOPE/CHEMS) anionic
      liposomes, at a constant lipid to DNA ratio, an increase in the polycation/DNA
      (N/P) ratio resulted in an increase in transfection activity. Meanwhile, the
      optimal lipid to DNA ratio for efficient gene delivery was influenced by the N/P
      ratio used, and was increased at higher N/P ratios. For the DNA condensing agent,
      poly-L-lysine could be replaced by polyethylenimine (PEI) as the DNA condensing
      agent in the formulations. For the lipidic components, CHEMS could be replaced by
      other anionic lipids including oleic acid, dicetylphosphate and
      phosphatidylserine, but DOPE, a fusogenic helper lipid, could not be replaced by
      dioleolyphosphatidylcholine. LPDII formulation showed significantly less
      cytotoxicity compared to the commonly used cationic lipsomes or PEI mediated
      transfection and several cell lines were transfected with high efficiency. LPDII
      vectors avoid the use of toxic cationic lipids and may have potential application
      in gene therapy.

PMID- 11332604
TI  - Adrenergic responses in human small arteries isolated from the femoral neck.
AB  - Many pathological bone conditions are accompanied by changes in bone perfusion.
      However, no method has yet allowed investigation of vascular reactivity in human
      bone tissue. In the present study, arterial segments (diameter approximately 0.25
      mm) were isolated from human bone biopsies and mounted as ring preparations in
      vitro. The viability of the arteries and the effects of adrenoceptor stimulations
      were investigated. Combined alpha- and beta-adrenoceptor stimulation
      (noradrenaline 10(-8)-10(-5) M) and specific alpha1-adrenoceptor stimulation
      (phenylephrine, 10(-8)-10(-4.5) M) induced concentration-dependent contractions
      in all arteries. Selective stimulation of alpha2-receptors (B-HT 933, 10(-8)-10(
      3.5) M) only induced contraction in three of eight arteries. Stimulation of beta
      receptors with isoprenaline (10(-6) M) resulted in vasorelaxation in 3 of 10
      arteries. In all arteries, acetylcholine (10(-10)-10(-5) M) induced
      vasorelaxation, demonstrating preserved function of the endothelium. The results
      suggest that primarily alpha1-receptors are responsible for adrenoceptor induced
      vasoconstriction in human bone while functional alpha2- and beta-receptors may
      not be consistently expressed. The model is the first to allow investigations on
      vascular reactivity in human bone tissue and may become valuable for assessment
      of both normal and pathological bone physiology.

PMID- 11332605
TI  - The effect of dynamic compression on the response of articular cartilage to
      insulin-like growth factor-I.
AB  - Articular cartilage is routinely subjected to mechanical forces and to cell
      regulatory molecules. Previous studies have shown that mechanical stimuli can
      influence articular chondrocyte metabolic activity, and biochemical studies have
      shown that growth factors and cytokines control many of the same cell functions.
      Little is known, however, of the relationships or interplay, if any, between
      these two key components of the articular environment. This study investigated
      the comparative and interactive effects of low amplitude, sinusoidal, dynamic
      compression and insulin-like growth factor-I (IGF-I), a polypeptide in synovial
      fluid that is anabolic for cartilage. In bovine patellofemoral cartilage
      explants, IGF-I increased protein and proteoglycan synthesis 90% and 120%,
      respectively while dynamic compression increased protein and proteoglycan
      synthesis 40% and 90%, respectively. Stimulation by IGF-I was significantly
      greater than by dynamic compression for both protein and proteoglycan synthesis.
      When applied together, the two stimuli enhanced protein and proteoglycan
      synthesis by 180% and 290%, respectively, a degree greater than that achieved by
      either stimulus alone. IGF-I augmented protein synthesis with a time constant of
      12.2 h. Dynamic compression increased protein synthesis with a time constant of
      2.9 h, a rate significantly faster than that of IGF-I, suggesting that these
      signals act via distinct cell activation pathways. When used together, dynamic
      compression and IGF-I acted with a time constant of 5.6 h. Thus, dynamic
      compression accelerated the biosynthetic response to IGF-I and increased
      transport of IGF-I into the articular cartilage matrix, suggesting that, in
      addition to independently stimulating articular chondrocytes, cyclic compression
      may improve the access of soluble growth factors to these relatively isolated
      cells.

PMID- 11332606
TI  - The effect of surgical dissections on blood flow to the tibial tubercle.
AB  - Tibial tubercle transfer is often used for the treatment of patella maltracking.
      Because the periosteum of both sides of the tibia is stripped off along the
      tibial tubercle and then the bilateral cortices are transferred, this procedure
      may disturb the blood supply to the tibial tubercle. However, the blood supply to
      the tibial tubercle has not yet been clearly elucidated. The purpose of this
      study is to investigate the effect of surgical dissection on blood flow to the
      tibial tubercle in an animal model using a hydrogen washout technique. Eleven
      knees of nine mongrel dogs weighing from 7.0 to 19.1 kg were utilized. The blood
      flow was measured using a hydrogen washout technique. Before performing the
      surgical procedures, the control blood flow rate of the tibial tubercle averaged
      19.6 ml/min per 100 g of tissue. The blood flow rate did not significantly
      decrease after transecting the periosteum on the lateral side of the tibia alone
      (P > 0.05). After completing the tibial tubercle osteotomy, the blood flow rate
      averaged 11.5 ml/min per 100 g of tissue, which is a 25.3% decrease as compared
      with the value after transecting the periosteum on the lateral side of the tibia
      alone (P < 0.05). The blood flow rate significantly decreased to 3.4 ml/min per
      100 g of tissue after the distal periosteal transection and osteotomy of the
      distal cortex of the tibial tubercle (P < 0.05). The addition of a medial
      periosteal transection caused a complete arrest of the blood flow in 10 out of 11
      knees, or a 91.2% decrease as compared with the value after a distal periosteal
      transection and osteotomy of the distal cortex of the tibial tubercle (P < 0.05).

PMID- 11332607
TI  - Age- and gender-related changes in the cellularity of human bone marrow and the
      prevalence of osteoblastic progenitors.
AB  - Bone marrow harvested by aspiration contains connective tissue progenitor cells
      which can be induced to express a bone phenotype in vitro. The number of
      osteoblastic progenitors can be estimated by counting the colony-forming units
      which express alkaline phosphatase (CFU-APs). This study was undertaken to test
      the hypothesis that human aging is associated with a significant change in the
      number or prevalence of osteoblastic progenitors in the bone marrow. Four 2-ml
      bone marrow aspirates were harvested bilaterally from the anterior iliac crest of
      57 patients, 31 men (age 15-83) and 26 women (age 13-79). A mean of 64 million
      nucleated cells was harvested per aspirate. The mean prevalence of CFU-APs was
      found to be 55 per million nucleated cells. These data revealed a significant age
      related decline in the number of nucleated cells harvested per aspirate for both
      men and women (P = 0.002). The number of CFU-APs harvested per aspirate also
      decreased significantly with age for women (P = 0.02), but not for men (P = 0.3).
      These findings are relevant to the harvest of bone marrow derived connective
      tissue progenitors for bone grafting and other tissue engineering applications,
      and may also be relevant to the pathophysiology of age-related bone loss and post
      menopausal osteoporosis.

PMID- 11332608
TI  - Cyclic tensile stretch inhibition of nitric oxide release from osteoblast-like
      cells is both G protein and actin-dependent.
AB  - Recent reports indicate the alteration of nitric oxide (NO) synthesis with
      mechanical stress loaded on the osteoblast and NO is considered to have a
      significant role in mechanotransduction. We found the involvement of guanine
      nucleotide-binding regulatory proteins (G proteins), especially Gi, in stress
      inhibited NO release of osteoblast-like cells (JOR:17;593-597, 1999). To
      determine further the mechanism involved in this process, we measured c-Jun N
      terminal kinase/stress-activated protein kinase (JNK/SAPK) activity under cyclic
      tensile stretch loaded on osteoblast-like cells. Cyclic stretch significantly
      enhanced JNK/SAPK activity and pertussis toxin clearly reversed stress-enhanced
      JNK/SAPK activity. Cytochalasin D, actin microfilament disrupting reagent, also
      abolished the stress activation of JNK/SAPK. We propose a model for signaling
      events induced by cyclic tensile stretch, namely a transmembrane mechanosensor
      which couples Gi-protein, actin cytoskeleton and finally activates JNK/SAPK
      activity of osteoblasts.

PMID- 11332609
TI  - Type I and type III procollagen gene expressions in the early phase of ligament
      healing in rabbits: an in situ hybridization study.
AB  - The purpose of this study is to observe type I and type III procollagen gene
      expressions in the healing ligament using in situ hybridization histochemistry.
      The rabbit medial collateral ligaments were incised and harvested at 3, 7, 14,
      and 28 days postoperatively. The healing ligament showed increased expression of
      both procollagen genes through this period compared with the unoperated ligament.
      The peak expression level was observed at 7 or 14 days for type I and at 7 days
      for type III, respectively. The strongest expression of both genes was detected
      in the scar tissue created between the ends of the old ligament. Although type
      III procollagen gene expression was observed almost only in the newly created
      scar tissue, type I procollagen gene was expressed not only in the scar tissue,
      but also at the ends of the previously normal ligament. These results suggest
      that type I collagen synthesis begins shortly after ligament injury and occurs at
      the ends of the injured ligament as well as in the scar tissue, and that type III
      collagen is largely synthesized in the scar tissue around one week after injury
      but continues being synthesized for at least four weeks after injury.

PMID- 11332610
TI  - Temporal expression of nitric oxide synthase isoforms in healing Achilles tendon.
AB  - We investigated the temporal expressions of the three nitric oxide synthase (NOS)
      isoforms by semi-quantitative polymerase chain reaction (PCR) assays and by
      immunoblot analysis, following Achilles tendon transection in rats. Four days
      after injury, there were increases in the steady-state levels of mRNA for all
      three NOS isoforms, with peaks for the inducible isoform (iNOS) (23-fold
      increase) at day 4, the endothelial isoform (eNOS) (24-fold increase) at day 7
      and the neuronal isoform (bNOS) (seven-fold increase) at day 21. The temporal
      expression of NOS isoforms at a protein level was consistent with the results at
      the mRNA level. We have previously shown a five-fold increase in the NOS
      activity, as detected by 3H-arginine to 3H-citrulline conversion, at day 7
      postinjury. These findings indicate that all three NOS isoforms are expressed
      during tendon healing with differential expression patterns during the various
      phases of tendon healing. These findings may prove clinically relevant with
      respect to strategies for regulating tendon healing.

PMID- 11332611
TI  - The effects of reduced oxygen tension on cell proliferation and matrix synthesis
      in synovium and tendon explants from the rabbit carpal tunnel: an experimental
      study in vitro.
AB  - Local ischemia may play an important role in the development of tendon
      degeneration as well as entrapment neuropathies. In order to investigate the
      cellular effects of hypoxia on tendon and synovial tissue from the carpal canal,
      dose response effects of oxygen on cell proliferation and synthesis of matrix
      components were examined in segments of synovial and flexor digitorum profundus
      tendon from the carpal tunnel of rabbits during short term culture. Explants were
      incubated in airtight containers flushed with either 0%, 1%, 3%, 20% O2 plus 2%
      CO2 and N2 to balance and labeled with either 3H-thymidine or 3H-proline and 35S
      sulfate. Cell proliferation was significantly inhibited by hypoxia in synovium
      but not in tendon (P = 0.03). In parallel, the synthesis of non-collagenous
      proteins was significantly reduced in synovium but not in tendon (P = 0.006). In
      both tissues hypoxia significantly inhibited collagen synthesis. On the other
      hand, hypoxia had no significant effect on the synthesis of new proteoglycans as
      determined by 35S-sulfate incorporation. Hypoxia can inhibit cell proliferation
      and alter synthesis of matrix components in synovial tissue, but may only have
      minor effects on non-collagen protein synthesis in tendon explants from the
      carpal canal of rabbit forepaws.

PMID- 11332612
TI  - Alterations in the regulatory pathway involving p16, pRb and cdk4 in human
      chondrosarcoma.
AB  - The G1 regulatory pathway involving p16, pRb and cdk4 in the cell cycle has been
      investigated in human chondrosarcoma. The protein expression of p16, pRb and cdk4
      was analyzed by Western blot in cultured cells from eight chondrosarcomas and in
      two chondrosarcoma cell lines. Both cell lines and one other sample were negative
      for p16. Moreover, one of the cell lines was pRb-negative and showed a high
      expression of cdk4 as well. In the other cell line and in three other samples pRb
      of expected size were detected in addition to a shorter form of the protein. To
      further investigate the reasons for down-regulation of the p16 protein, the p16
      coding gene CDKN2 was analyzed by polymerase chain reaction (PCR), methyl
      specific PCR (MSP) and sequencing in all tumor samples as well as in
      corresponding tumor tissues from three of the samples. The p16-negative samples
      were all found to have homozygous deletion of CDKN2. Another sample showed
      partial gene methylation and a heterozygous position in codon 148 was detected in
      one sample. The same base substitution was also found in two of the tissue
      samples. Finally, cytogenetic analysis of the samples with homozygously deleted
      CDKN2 revealed multiple structural abnormalities in all three cases. In
      conclusion, the p16/pRb/cdk4 pathway may play an important role in the
      pathogenesis of some chondrosarcomas.

PMID- 11332613
TI  - Spread of infection, in an animal model, after intramedullary nailing of an
      infected external fixator pin track.
AB  - Implant sepsis. due to previous external fixator pin track infection, is the most
      common complication of secondary intramedullary (IM) nailing of the tibia. We
      have developed an animal model, which allows different treatment methods to be
      studied. Using an established ovine model of a pin track infection,
      Staphylococcus aureus was used to infect the external fixator pins, two weeks
      prior to reamed IM nailing. In the control group, the animals were killed at a
      mean of 10.5 days following nailing, when widespread infection was evident, with
      septic arthritis, abscess formation, and infection of the entire length of the
      tibia in all six animals. In the treatment group, before IM nailing, the pin
      sites were debrided, and both local and systemic antibiotics were administered.
      All surgical wounds healed without evidence of infection, 4 of the 6 animals
      survived for 28 days, and bacteria were only isolated from 1 of the 6 implants.
      Treatment was successful at reducing, but not eliminating, infection after
      secondary nailing.

PMID- 11332614
TI  - On the applicability of two different stimulation techniques for intra-operative
      peroneal nerve conduction testing.
AB  - Dysfunction of the peroneal nerve is an important complication of knee surgery.
      We compared two monitoring procedures of peroneal nerve function during a
      standardized operation, a closing wedge high tibial osteotomy. For two types of
      stimulation the evoked compound motor unit action potentials (CMAPs) were
      recorded on the tibialis anterior muscle. We used direct perineural electrical
      stimulation of the common peroneal nerve distal to the cuff (dCMAPs) after nerve
      identification in the surgical field. Additionally, magnetic stimulation of the
      sacral plexus proximal to the cuff (pCMAPs) was performed. It was found that
      dCMAPs were recorded during almost one hour of tourniquet time whereas the pCMAPs
      were blocked after 25-30 min in 9 out of 11 cases. On the other hand, the CMAP
      obtained after proximal stimulation exhibited a latency shift with tourniquet
      yielding an indicator of ischaemic changes present beneath and distal to the
      tourniquet cuff. In conclusion, different applicabilities of both stimulation
      techniques under tourniquet conditions were demonstrated.

PMID- 11332615
TI  - BMP signaling stimulates chondrocyte maturation and the expression of Indian
      hedgehog.
AB  - Mutant BMP receptors were transfected into cultured embryonic upper sternal
      chrondrocytes using retroviral vectors to determine if BMP signaling is required
      for chondrocyte maturation and the expression of a key regulatory molecule,
      Indian hedgehog (Ihh). Chondrocytes infected with replication competent avian
      retroviruses (RCAS) viruses carrying constitutive active (CA) BMPR-IA and BMPR-IB
      had enhanced expression of type X collagen and Ihh mRNA. Addition of PTHrP, a
      known inhibitor of chondrocyte maturation, abolished the expression of type X
      collagen, BMP-6, and Ihh mRNAs in control cells. In contrast, PTHrP treated
      cultures infected with of CA BMPR-IA or CA BMPR-IB had low levels of BMP-6 and
      type X collagen, but high levels of Ihh expression. Although dominant negative
      (DN) BMPR-IA had no effect, DN BMPR-IB inhibited the expression of type X
      collagen and BMP-6, and decreased alkaline phosphatase activity, even in the
      presence of exogenously added BMP-2 and BMP-6. DN BMPR-IB also completely blocked
      Ihh expression. Overall, the effect of DN BMPR-IB mimicked the effects of PTHrP.
      To determine if there is an autocrine role for the BMPs in chondrocyte
      maturation, the cultures were treated with noggin and follistatin, molecules that
      bind BMP-2/-4 and BMP-6/-7, respectively. While noggin and follistatin inhibited
      the effects of recombinant BMP-2 and BMP-6, respectively, they had only minimal
      effects on the spontaneous maturation of chondrocytes in culture, suggesting that
      more than one subgroup of BMPs regulates chondrocyte maturation. The results
      demonstrate that: (i) BMP signaling stimulates chondrocyte maturation; (ii) BMP
      signaling increases Ihh expression independent of maturational effects; and (iii)
      BMP signaling can partially overcome the inhibitory effects of PTHrP on
      maturation.

PMID- 11332616
TI  - Collagen gene expression and mechanical properties of intervertebral disc cell
      alginate cultures.
AB  - Cells of the intervertebral disc have a limited capacity for matrix repair that
      may contribute to the onset and progression of degenerative disc changes. In this
      study, the biosynthetic capacity of cells isolated from specific regions of the
      porcine intervertebral disc was evaluated in vitro. Using a competitive reverse
      transcription-polymerase chain reaction technique, gene expression levels for
      types I and II collagen were quantified in cells cultured for up to 21 d in a
      three-dimensional alginate culture system and compared to levels obtained for
      cells in vivo. The mechanical properties of cell-alginate constructs were
      measured in compression and shear after periods of culture up to 16 weeks. Cells
      from the anulus fibrosus expressed the most type I collagen mRNA in vivo and in
      vitro, while cells from the transition zone expressed the most type II collagen
      mRNA in vivo and in vitro. Mechanical testing results indicate that a
      mechanically functional matrix did not form at any time during the culture
      period; rather, decreases of up to 50% were observed in the compressive and shear
      moduli of the cell-alginate constructs compared to alginate with no cells.
      Together with results of prior studies, these results suggest that intervertebral
      disc cells maintain characteristics of their phenotype when cultured in alginate,
      but the molecules they synthesize are not able to form a mechanically functional
      matrix in vitro.

PMID- 11332617
TI  - Exogenous insulin-like growth factor-I stimulates an autoinductive IGF-I
      autocrine/paracrine response in chondrocytes.
AB  - The modulation of insulin-like growth factor-I (IGF-I) gene expression by
      chondrocytes following exogenous IGF-I supplementation of culture was assessed to
      examine the hypothesis that constitutive IGF-I mRNA activity is suppressed by
      exogenous administration of IGF-I to cartilage in situ. Chondrocytes in monolayer
      culture were treated with 0, 10 or 100 ng/ml IGF-I for 48 h and resultant IGF-I
      and matrix gene expression patterns were assessed by quantitative polymerase
      chain reaction (qPCR) and northern blotting, respectively. Effective translation
      of proteoglycan (PG) as a response to IGF-I was determined by dimethylmethylene
      blue (DMMB) dye-binding assay. To determine the temporal nature of the IGF-I
      autocrine/paracrine response to exogenous IGF-I, chondrocyte cultures were
      treated with 100 ng/ml IGF-I and the IGF-I mRNA response was assessed at 0, 4,
      12, 24, 48 and 72 h. Significant increases in chondrocyte density and in PG
      synthesis occurred during treatment of chondrocyte cultures with 10 and 100 ng/ml
      IGF-I. Persistent exposure of chondrocytes to 100 ng/ml IGF-I resulted in maximal
      IGF-I mRNA response at 24 h, with declining message accumulation at 48 and 72 h.
      These data suggest that IGF-I induces an autoinductive IGF-I autocrine/paracrine
      transcriptional response. The clinical ramifications of these findings include
      support for the use of exogenous IGF-I for cartilage repair where it could
      conceivably amplify and extend the effect of exogenous IGF-I beyond the
      transitory persistence of supplemental IGF-I ligand in repair constructs.

PMID- 11332618
TI  - Degradation of the cartilage collagen matrix associated with changes in
      chondrocytes in osteoarthrosis. Assessment by loss of background fluorescence and
      immunodetection of matrix components.
AB  - Articular cartilage damage and eventual loss is the primary pathological change
      seen in osteoarthrosis (OA). In this study we have investigated the link between
      turnover of the collagen matrix and changes in chondrocytes. The background
      fluorescence of articular cartilage, as indicated by its emission spectrum and
      resistance to extraction was generated by the slow non-enzymic modification of
      the collagen matrix by advanced glycation end products (AGEs). Assessment of
      changes in background fluorescence in sections of articular cartilage provided a
      narrative of collagen degradation. Patients without OA pathology typically had a
      uniform strong background fluorescence throughout the depth of the cartilage.
      Cartilage from OA patients showed a range of changes in background fluorescence
      dependent on depth from the articular surface and proximity to overt lesions.
      Loss of background fluorescence was centered on chondrocytes, more extensive near
      the surface and associated with detection of the proteoglycan epitope 7D4.
      Expression of type X collagen was seen in articular cartilage in the region of
      the interface of with subchondral bone in most OA patients but was not associated
      with prominent, pericellular, loss of background fluorescence. These observations
      are consistent with progressive cartilage damage in OA, whereby collagen turnover
      and loss of surface integrity is associated with chondrocyte activity similar to
      that seen in immature articular cartilage.

PMID- 11332619
TI  - Both retinoic acid and 1,25(OH)2 vitamin D3 inhibit thyroid hormone-induced
      terminal differentiaton of growth plate chondrocytes.
AB  - Thyroid hormone has been known for over 50 years to be a potent regulator of
      skeletal maturation at the growth plate. The receptor for thyroid hormone has
      been discovered to be a member of the nuclear hormone receptor superfamily.
      Retinoic acid and 1,25(OH)2 vitamin D3, whose receptors also belong to this
      nuclear hormone receptor family, have been implicated in the control of
      chondrocyte proliferation and differentiation at the growth plate. Recent studies
      demonstrate that the receptors for thyroid hormone, retinoic acid, and vitamin D
      bind to a similar DNA response element in the promoter region of target genes and
      may form heterodimers to regulate gene transcription in target cells. These
      observations led us to hypothesize that the retinoic acid and/or vitamin D
      signaling pathways may interact with thyroid hormone signaling at the molecular
      level to modulate growth plate chondrocyte differentiation. Using a chemically
      defined, serum-free model of growth plate chondrocyte maturation, both all-trans
      retinoic acid and 1,25(OH)2 vitamin D3 markedly inhibited thyroid hormone-induced
      terminal differentiation in a dose-dependent manner. In the absence of thyroid
      hormone, retinoic acid stimulated alkaline phosphatase activity modestly at the
      highest dose used, however neither retinoic acid nor 1,25(OH)2 vitamin D3 induced
      expression of type X collagen mRNA. We conclude that retinoic acid and vitamin D
      are likely to be antagonists of thyroid hormone signaling in the growth plate.

PMID- 11332620
TI  - Development, test reliability and validation of a classification for revision hip
      arthroplasty.
AB  - The objective of the study was to develop a valid and reliable classification
      system for failed hip arthroplasties. The study uses research principals derived
      from multi-attribute utility theory and consensus group techniques. The
      development of the severity measure was done in two phases. Phase I of the study
      included: (a) questionnaire development, (b) submission of the questionnaire to
      the respondents, (c) data synthesis of the responses and item reduction, and (d)
      classification development and inter-observer reliability testing. Phase II
      included: (a) resubmission of the instrument to the respondents for
      suggestions/feedback, (b) instrument revision by the co-investigators based on
      the respondents' second feedback, and (c) inter-observer reliability testing and
      intraoperative validity testing of the instrument. The questionnaires sought to
      capture expert opinion as to what clinical determinants obtained preoperatively
      (during patient interview, physical exam and review of plain radiographs - AP
      pelvis and hip lateral) that would in their clinical experience reveal
      intraoperative severity. There was an 80% (16/20) response rate from the outside
      experts invited to participate in the study. Based on item reduction and test
      retest analysis, a five-grade radiographic classification for the acetabulum as
      well as the femur was developed. This system was then reviewed by 13 of the
      initial outside experts (16, 80%) who participated in the first round. Inter
      rater reliability testing of the final format of the classification revealed a
      weighted kappa statistic value of 0.88 between the two-blinded raters (inter
      rater reliability) and 0.87 between the blinded raters and the reference standard
      (intraoperative validity). We conclude that the study developed a reliable and
      valid radiographic classification system for failed hip arthroplasty.

PMID- 11332621
TI  - Stress analysis of the distal locking screws for femoral interlocking nailing.
AB  - In femoral locked nailing, the distal locking screws are vulnerable to mechanical
      failure. Biomechanical studies have shown that the stress on these screws is
      substantially affected by the fit of the nail in the medullary canal. In this
      study, a "closed form" mathematical model based on elastic beam-column theory was
      developed to investigate how the nail-cortical contact, which was simulated by a
      linear elastic foundation, affected the stress on the distal locking screws.
      Providing data for the model was a construct of a fractured femur with an
      intramedullary locked nail loaded by an eccentric vertical load. The stress on
      the locking screw was analyzed as a function of the distance from the fracture to
      the locking screw in the distal fragment under two situations: with and without
      nail-cortical contact in the distal fragment. With nail-cortical contact, the
      screw stress decreased as the length of nail-cortical contact and the distance
      between the distal locking screw and the fracture site increased, but this stress
      contrarily increased when the nail reached the femoral region at which the screw
      length increased. The screw stress was much higher without nail-cortical contact
      than with contact and continued to increase as the nail was inserted further. The
      mathematical model developed here can be a convenient means of rapid stress
      evaluation and parametric analysis for locked femoral nailing. It may be used to
      improve the design of interlocking nails and surgical technique.

PMID- 11332622
TI  - Development of tensile strength during distraction osteogenesis in a rat model.
AB  - These studies were designed to determine the reliability of in vitro tensile
      testing to measure the temporal development of regenerate bone strength in rats
      during limb lengthening (distraction osteogenesis, DO). External fixators were
      placed on the right tibiae of 36 virus-free, 400-450 g male Sprague Dawley rats,
      and osteotomies (n = 33) were performed. Distraction was initiated the following
      morning (0 day latency) at 0.4 mm/day and continued to day 20. The 8 mm gap was
      allowed to consolidate for up to 50 days (day 70 postop). Contralateral
      unoperated and operated (fixator only) controls were included. On days 20, 30, 50
      and 70 postop, the rats were anesthetized, and their tibiae were radiographed
      prior to undergoing sacrifice for histological or tensile analysis. On day 70, an
      additional group was tested by three-point bending. Radiodensity measurements
      demonstrated progressive mineralization of the DO gap, and histology confirmed
      typical intramembranous ossification of collagen bundles oriented parallel to the
      distraction force. Tensile stiffness increased significantly between days 20 and
      30 postop, this increase correlated with initial radiographic and histologic
      bridging of the DO gap. Energy to failure and ultimate tensile strength increased
      progressively to day 70. At day 70, the force to failure for three-point bending
      was 65% of control tibiae. In conclusion, in vitro tensile testing provides a
      reliable method to test the development of structural integrity during the early
      stages of DO. Therefore, the biomechanical effects of postulated modulators of
      bone repair can be measured during early stages (bone formation, bridging, early
      consolidation) of DO in a rat model.

PMID- 11332623
TI  - Peripheral nerve lengthening by controlled isolated distraction: a new animal
      model.
AB  - We have developed a simple and effective animal model to study the distraction
      neurogenesis utilizing the sciatic nerve-lengthening technique in rats. The model
      allows macroscopic, physiological, and histological evaluation of the distraction
      site. Fourteen adult Harlan Sprague Dawley rats (300-350 g) were used in this
      study. A 10 mm segment of the right sciatic nerve of each animal in the nerve
      lengthening group was resected. Gradual nerve lengthening was performed by
      advancing the proximal nerve stump at a rate of 1 mm/day. The proximal stump
      neuroma was then resected and a direct nerve anastomosis was performed. On the
      left side a standard autogenous nerve-grafting procedure was performed with a 10
      mm segment of sciatic nerve used as an in situ nerve graft. Three months after
      the second surgery, the sciatic nerves were exposed and investigated by gross
      observation and EMG followed by histological processing and tissue analysis.
      Neomicrovascularization was observed surrounding the sciatic nerve anastomosis in
      all five specimens of the nerve-lengthening group as compared to the more white
      colored scar tissue that was observed in the nerve-grafting group. The EMG
      results were similar for both groups. Histological studies of the lengthened
      nerves showed axon morphology equivalent to the grafted nerves. This study
      demonstrated a clear evidence of the successful nerve regeneration within a
      segmental nerve gap by nerve lengthening.

PMID- 11332624
TI  - Molecular aspects of healing in stabilized and non-stabilized fractures.
AB  - Bone formation is a continuous process that is initiated during fetal development
      and persists in adults in the form of bone regeneration and remodeling. These
      latter two aspects of bone formation are clearly influenced by the mechanical
      environment. In this study we tested the hypothesis that alterations in the
      mechanical environment regulate the program of mesenchymal cell differentiation,
      and thus the formation of a cartilage or bony callus, at the site of injury. As a
      first step in testing this hypothesis we produced stabilized and non-stabilized
      tibial fractures in a mouse model, then used molecular and cellular methods to
      examine the stage of healing. Using the "molecular map" of the fracture callus,
      we divided our analyzes into three phases of fracture healing: the inflammatory
      or initial phase of healing, the soft callus or intermediate stage, and the hard
      callus stage. Our results show that indian hedgehog(ihh), which regulates aspects
      of chondrocyte maturation during fetal and early postnatal skeletogenesis, was
      expressed earlier in an non-stabilized fracture callus as compared to a
      stabilized callus. ihh persisted in the non-stabilized fracture whereas its
      expression was down-regulated in the stabilized bone. IHH exerts its effects on
      chondrocyte maturation through a feedback loop that may involve bone
      morphogenetic protein 6 [bmp6; (S. Pathi, J.B. Rutenberg, R.L. Johnson, A.
      Vortkamp, Developmental Biology 209 (1999) 239-253)] and the transcription factor
      gli3. bmp6 and gli3 were re-induced in domain adjacent to the ihh-positive cells
      during the soft and hard callus stages of healing. Thus, stabilizing the
      fracture, which circumvents or decreases the cartilaginous phase of bone repair,
      correlates with a decrease in ihh signaling in the fracture callus. Collectively,
      our results illustrate that the ihh signaling pathway participates in fracture
      repair, and that the mechanical environment affects the temporal induction of
      ihh, bmp6 and gli3. These data support the hypothesis that mechanical influences
      affect mesenchymal cell differentiation to bone.

PMID- 11332625
TI  - Locally delivered rhTGF-beta2 enhances bone ingrowth and bone regeneration at
      local and remote sites of skeletal injury.
AB  - The purposes of the present study were to determine if recombinant human
      transforming growth factor-beta-2 (rhTGF-beta2) enhances bone ingrowth into
      porous-coated implants and bone regeneration in gaps between the implant and
      surrounding host bone. The implants were placed bilaterally for four weeks in the
      proximal humeri of skeletally mature, adult male dogs in the presence of a 3-mm
      gap. In three treatment groups of animals, the test implant was treated with
      hydroxyapatite/tricalcium phosphate (HA/TCP) and rhTGF-beta2 in buffer at a dose
      per implant of 1.2 microg (n = 6), 12 microg (n = 7), or 120 microg (n = 7) and
      placed in the left humerus. In these same animals, an internal control implant
      treated only with HA/TCP and buffer was placed in the right humerus. In a non-TGF
      beta treated external control group of animals (n = 7), one implant was treated
      with HA/TCP while the contralateral implant was not treated with the ceramic. In
      vitro analyses showed that approximately 15%, of the applied dose was released
      within 120 h with most of the release occurring in the first 24 h. The TGF-beta
      treated implants had significantly more bone ingrowth than the controls with the
      greatest effect in the 12 microg/implant group (a 2.2-fold increase over the
      paired internal control (P = 0.004) and a 4-fold increase over the external
      control (P < 0.001)). The TGF-beta treated implants had significantly more bone
      formation in the gap than the controls with the greatest effect in the 12 and 120
      microg groups (1.8-fold increases over the paired internal controls (P = 0.003
      and P = 0.012, respectively) and 2.8-fold increases over the external controls (P
      < 0.001 and P = 0.001, respectively)). Compared to the external controls, the
      internal control implants tended to have more bone ingrowth (1.9-fold increase, P
      = 0.066) and had significantly more bone formation in the gap (1.7-fold increase.
      P = 0.008). Thus, application of rhTGF-beta2 to a porous-coated implant
      stimulated local bone ingrowth and gap healing in a weakly dose-dependent manner
      and stimulated bone regeneration in the 3-mm gap surrounding the contralateral
      control implant, a site remote from the local treatment with the growth factor.

PMID- 11332626
TI  - The chondrogenic potential of periosteum decreases with age.
AB  - Periosteum contains undifferentiated mesenchymal stem cells that possess the
      potential for chondrogenesis during cartilage repair and in fracture healing.
      With aging, the chondrogenic potential of periosteum declines significantly. An
      organ-culture model was used to investigate the relationship between the
      chondrogenic potential of periosteum and aging. A total of 736 periosteal
      explants from the proximal medial tibiae of 82 rabbits, aged 2 weeks to 2 years,
      were cultured in agarose suspension conditions conductive for chondrogenesis. and
      analyzed using histomorphometry, collagen typing, wet weight measurement, 3H
      thymidine and 35S-sulfate uptake, autoradiography, and PCNA immunostaining. The
      rabbits were skeletally mature by 6 months and stopped increasing in weight by 12
      months. Chondrogenesis declined significantly with age (P < 0.0001) and was
      maximal in the 1.5-2 month-old rabbits. Explants from the 6 month-old rabbits
      formed 50% less cartilage. and by 12 months chondrogenesis reached a steady state
      minimal level. In parallel with this decrease in chondrogenic potential similar
      decreases were measured in 3H-thymidine uptake (P < 0.0001). 35S-sulfate uptake
      (P = 0.0117), as well as the thickness (P < 0.0001) and the total number of cells
      in the cambium layer of the periosteum (P < 0.0001). Autoradiography with 3H
      thymidine and PCNA immunostaining confirmed the measured decrease in
      proliferative activity in the cambium layer where the chondrocyte precursors
      reside, although the percentage of proliferating cells did not change
      significantly with age. The most dramatic change was the marked decrease (87%) in
      the thickness and total cell number in the cambium layer of the perisoteum
      between the 2 and 12 month-old rabbits (P < 0.05). These data confirm a decline
      in the chondrogenic potential of periosteum with aging. Thus, one possibility for
      improving cartilage formation by periosteal transplantation after skeletal
      maturity would be to stimulate an increase in the total number of cells in the
      chondrocyte precursor pool early during chondrogenesis.

PMID- 11332627
TI  - Cell therapy for diabetes using piscine islet tissue.
AB  - The islet tissue, called Brockmann bodies, in certain teleost fish is
      anatomically distinct from the pancreatic exocrine tissue and can be easily
      identified macroscopically. Expensive islet isolation procedures, such as
      required when procuring islet tissue from mammalian pancreases, are unnecessary.
      Tilapia islets transplanted into diabetic athymic nude mice will produce long
      term normoglycemia and mammalian-like glucose tolerance profiles. Encapsulated
      tilapia islets function well after transplantation into euthymic recipients.
      Additionally, tilapia are potentially ideal xenogeneic donors because of markedly
      lower donor production costs, minimal islet procurement costs, and possibly
      decreased xenozoonotic potential relative to mammalian donors. Tilapia islets
      appear to be appropriately glucose responsive with high insulin output, can be
      cryopreserved, and are much more resistant to hypoxia than mammalian islets.
      Because tilapia and human insulin differ by 17 amino acids, we have cloned,
      sequenced, and modified the tilapia insulin gene by site-directed mutagenesis
      resulting in a tilapia insulin gene that codes for "humanized" insulin while
      still maintaining all of the tilapia regulatory (noncoding) sequences. We have
      now produced small numbers of founder transgenic tilapia with incorporation of
      our humanized tilapia insulin gene construct, and we have shown transmission and
      expression of the transgene in the beta cells and serum of their Fl offspring.
      Our ultimate goal is to achieve homologous recombination and to breed for
      homozygosity for the hybrid insulin gene. Subsequent generations of transgenic
      tilapia will undergo a program of genomic optimization selecting for growth,
      survival, and fecundity as well as stability of the transgene. Islets from the
      resulting transgenic fish, after extensive characterization, could be harvested,
      encapsulated, and then transplanted into diabetic patients.

PMID- 11332628
TI  - Surviving native beta-cells determine outcome of syngeneic intraportal islet
      transplantation.
AB  - In moderately diabetic rats (plasma glucose 20-30 mmol/L), where there is some
      residual pancreatic islet function, normoglycemia can be restored by
      transplantation of pancreatic islets into the liver via the portal vein. To
      examine whether normoglycemia can also be achieved in more severely diabetic
      animals (which more closely resemble human type I diabetes), we have compared the
      effect of transplanting 1000 islets intraportally in Lewis rats made moderately
      diabetic (55 mg/kg streptozotocin injected IP while nonfasting) or severely
      diabetic (65 mg/kg streptozotocin injected IP while fasting). In the moderately
      diabetic rats in which residual pancreatic insulin was 128 +/- 40 mU insulin
      (2.0% of control), plasma glucose stabilized (32 +/- 2.8 mmol/L at 1 week, 34 +/-
      2 mmol/L at 3 weeks) as did body weight (falling from 290 +/- 5 to 265 +/- 5 g at
      1 week and 253 +/- 6 g at 3 weeks). In contrast, in severely diabetic rats in
      which residual pancreatic insulin was only 13.5 +/- 4.2 mU insulin (0.21% of
      control), there was a progressive rise in plasma glucose (30 +/- 1.3 mmol/L at 1
      week, 49 +/- 4 mmol/L at 2 weeks, and 67 +/- 7 mmol/L at 3 weeks) and a
      progressive fall in body weight (from 304 +/- 10 to 260 +/- 5 g by week 1 and to
      209 +/- 6 g by week 3). Following islet transplantation, nonfasting plasma
      glucose normalized in moderately diabetic rats (10.5 +/- 0.6 vs. 9.1 +/- 0.6
      mmol/L in nondiabetic controls, NS) after 23 +/- 5 days. In contrast, in the
      severely diabetic rats plasma glucose stabilized at 32 +/- 5 mmol/L (p < 0.05
      compared to moderately diabetic group) but did not normalize. This difference was
      not attributable to different plasma glucose levels at the time of
      transplantation (35.1 +/- 1.8 in moderately diabetic vs. 32.5 +/- 2.5 mmol/L in
      severely diabetic rats). These observations demonstrate that residual native beta
      cells (equivalent to only 60-80 islets) contribute to the survival or function of
      intraportally transplanted islets.

PMID- 11332629
TI  - Comparative functional study of clonal insulin-secreting cells cultured in five
      commercially available tissue culture media.
AB  - The electrofusion-derived rat insulin-secreting cell line BRIN-BD11 was cultured
      in five different commercially available media to determine the optimum medium
      for the in vitro maintenance of such clonal cell lines. Cells were cultured in
      RPMI-1640, DMEM, McCOY'S, F-12K, or MEM culture medium supplemented with 10%
      (v/v) fetal bovine serum and antibiotics (100 U/ml penicillin and 0.1 g/L
      streptomycin). Insulin secretion studies performed after 10 days revealed RPMI
      1640 to be the best performing medium in terms of insulin secretory
      responsiveness to a range of stimuli including glucose, L-alanine, L-arginine,
      carbachol, and glibenclamide. Insulin release was significantly decreased (p <
      0.01 to p < 0.05) in all other media compared to RPMI-1640. Only the cells
      cultured in RPMI-1640 and DMEM showed a significant glucose-induced insulin
      secretory response (p < 0.01 and p < 0.05). McCOY'S gave the next best result
      followed by F-12K and MEM. After the 10-day culture period, the highest insulin
      content was found in cells cultured in RPMI-1640 and DMEM with significantly
      lower levels of insulin in cells cultured in McCOY'S, F-12K, and MEM (p < 0.01 to
      p < 0.001). RPMI-1640 was used for further studies to investigate the effects of
      5.6-16.7 mmol/L glucose in culture on the secretory responsiveness of BRIN-BD11
      cells. Significant responses to a number of nonglucidic secretagogues were seen
      following culture at 5.6 and 16.7 mmol/L glucose, although responsiveness was
      less than after culture with 11.1 mmol/L glucose. At 16.7 mmol/L glucose culture,
      glucose-stimulated insulin release was abolished.

PMID- 11332630
TI  - Posttranscriptional mechanisms of glucocorticoid antiproliferative effects:
      glucocorticoids inhibit IL-6-induced proliferation of B9 hybridoma cells.
AB  - Addition of rIL-6 to IL-6-dependent B9 cells starved for IL-6 for 16-20 h
      stimulated a vigorous proliferative response. Glucocorticoids (GCs), in a
      concentration-dependent manner, inhibited rIL-6-stimulated proliferation of B9
      cells This inhibition was specific for the GCs, evident by the capacity of the
      GCs, dexamethasone, prednisolone, and hydrocortisone, but not non-GC steroids, to
      suppress rIL-6-dependent B9 cell proliferation. Furthermore, GC inhibition of IL
      6-stimulated B9 cell proliferation was receptor mediated and was abrogated by the
      GC receptor antagonist, RU486. In addition to their reported effects on
      inhibition IL-6 expression, the results presented support the notion that GCs
      also acted distally by suppressing signal transduction through the IL-6 receptor.

PMID- 11332631
TI  - C-Peptide determinations in islet xenotransplantation: A study in the pig-to
      mouse model.
AB  - Assays of C-peptide are used to monitor allogeneic islet graft function. However,
      it is not known whether xenogeneic C-peptide is metabolized and excreted in a
      fashion similar to endogenous and allogeneic C-peptide. In this study, injection
      of 10 times the physiological amount of porcine C-peptide into mice did not
      result in the excretion of the C-peptide in the urine. In contrast, when a
      physiological amount of porcine C-peptide was injected into athymic mice, urinary
      excretion of porcine C-peptide was readily detected. After injection of
      radioactively labeled porcine C-peptide into mice, the radioactive uptake in
      tissues belonging to the mononuclear phagocytic system was significantly
      increased in mice immunized towards the xenogeneic C-peptide. These results may
      reflect an immunological reactivity towards the C-peptide. Antibodies against
      porcine C-peptide could not be detected in the serum of any of the mice. However,
      porcine C-peptide was found to be glycosylated. Thus, a possible explanation to
      the lack of porcine C-peptide in the urine is that xenoreactive antibodies had
      bound to carbohydrate structures on the peptide and that the antibody-C-peptide
      complex had been cleared from the circulation by the mononuclear phagocytic
      system. Thus, the urinary excretion of xenogeneic C-peptide seems to be different
      from that of endogenous and allogeneic C-peptide. Consequently, determinations of
      donor-specific C-peptide may not properly reflect islet xenograft function. In
      fact, islet xenograft function may be underestimated.

PMID- 11332632
TI  - Enhanced survival of grafts genetically endowed with the ability to block CD2 and
      B7.
AB  - In a model of transplantation rejection, we have tested whether a graft
      manipulated to secrete immunomodulators could protect itself from immune
      destruction. An insulinoma cell line having the NOD genotype but also expressing
      the neoantigen, SV40 T antigen, was transfected with CTLA4Ig or LFA3Ig to block
      signals in the co-stimulatory/adhesion pathways. This neoantigen is potent at
      inducing graft rejection. Secretion of CTLA4Ig and LFA3Ig by transfectants
      promoted survival of the insulinoma graft in young NOD mice. In immunodeficient
      mice, cell growth was similar for all transfectants. However, in immunocompetent
      NOD mice the survival/growth of test grafts was significantly better than that of
      the controls. Graft survival was enhanced additively, when the two test
      transfectants were cotransplanted. Endowing the graft the ability to secrete
      immunomodulators that block individual co-stimulatory/adhesion signals can
      contribute to transplantation success. Blockade of two signals (CD2 and CD28) in
      these pathways enhances this success.

PMID- 11332633
TI  - Protection of xenografts by a combination of immunoisolation and a single dose of
      anti-CD4 antibody.
AB  - Immunoisolation is the separation of transplanted cells from cells of the immune
      system using a semipermeable membrane. Using one such immunoisolation capsule-the
      TheraCyte device-we have assessed the survival of encapsulated xenogeneic tissue
      in vivo as well as the contribution of CD4+ve T cells to encapsulated xenograft
      rejection. The foreign body reaction to the TheraCyte capsule in vivo was
      assessed by transplanting empty capsules into normal mice. These capsules elicit
      a foreign body response by the host animal. Encapsulated CHO, NIT-1, and PK-15
      cells were placed in culture and in immunodeficient mice to investigate their
      growth characteristics in the TheraCyte device. These cell lines survive both in
      culture and in immunodeficient SCID mice. Xenogeneic PK cells were also
      transplanted into normal C57BL/6 mice. These cells do not survive in normal mice
      despite the absence of direct contact between infiltrating and encapsulated
      cells. In addition, the survival of encapsulated cells in mice treated with a
      single dose of anti-CD4 antibody was examined. This was assessed using two
      systems: 1) histological analysis of capsule sections; 2) a quantitative
      luciferase reporter system using PK cells transfected to express luciferase. In
      both cases, anti-CD4 antibody contributed to prolonged encapsulated xenogeneic
      cell survival. Encapsulated xenogeneic cells survive in immunodeficient mice but
      not normal mice. Treatment of normal mice with anti-CD4 antibody results in
      prolonged survival of xenogeneic cells that can be measured using a luciferase
      reporter system. These results highlight the contribution of CD4+ve T cells to
      encapsulated xenograft rejection.

PMID- 11332634
TI  - Chitosan-polyvinyl pyrrolidone hydrogel does not activate macrophages: potentials
      for transplantation applications.
AB  - We have shown previously that chitosan-polyvinyl pyrrolidone (PVP) hydrogels are
      blood compatible, islet compatible, and noncytotoxic to various cell types.
      Because of these potential applications of chitosan-PVP hydrogel, the present
      study was designed to investigate its effect on macrophage activation.
      Macrophages did not adhere to hydrogel in culture but maintained their viability
      and did not undergo apoptosis as confirmed by trypan blue staining and absence of
      DNA ladder. Hydrogel leach-out products did not exhibit cytotoxic effects on
      macrophage functionality at mitochondrial and lysosomal level as confirmed by
      tetrazolium reduction (MTT) and neutral red uptake (NRU) assay. On exposure to
      hydrogels, macrophages showed comparable expression of activation markers such as
      CDllb/CD18 (Mac-1), CD45, and CD14 to those cultured in the presence of PTFE, a
      known biocompatible control, indicating its nonactivating nature. Macrophage
      activation was also assessed by checking the level of messenger RNA of
      inflammatory cytokines such as IL-6 and TNF-alpha by reverse transcriptase
      polymerase chain reaction (RT-PCR), which did not show stastistically significant
      difference (p > 0.05) in the expression of these transcripts in both control and
      hydrogel-exposed macrophages. The nonimmunogenic nature of the hydrogel was
      further confirmed by the lack of induced proliferation of mouse splenic
      lymphocytes after exposure to hydrogel leach-outs. All these results point out
      that chitosan-PVP hydrogel did not activate macrophages and thus is
      immunocompatible. Our results indicate that this hydrogel could be a potential
      candidate for transplantation studies by virtue of its biocompatibility and
      imunocompatibility.

PMID- 11332635
TI  - Characteristics of cartilage biopsies used for autologous chondrocytes
      transplantation.
AB  - Biopsies removed from 57 patients considered for cartilage transplantation were
      grown at CTI Ltd. (47 biopsies) and at Tel Aviv University (10 biopsies). Tissue
      processing took place in dedicated laboratories. Explant cultures allowed cell
      number expansion. Fifty-four out of 57 biopsies grew cells. Fanning out of the
      cells began after 5-15 days in culture. Two passages later, cell numbers in the
      10(7) range were achieved. Cells from all cultures expressed mRNA of aggrecan and
      link protein but not of alkaline phosphatase. Histochemical stains such as alcian
      blue pH 1 were negative in sparse monolayer cultures, but positive in pellet
      cultures. Immunohistochemistry demonstrated expression of collagen type I in
      monolayer cultures, switching to collagen type II in micromass cultures.
      Fibroblast growth factor receptor 3, a recently described characteristic receptor
      of precartilaginous cells, was expressed in monolayers and disappeared in
      micromass cultures. In conclusion, explants of articular chondrocytes cultured in
      vitro consistently yield monolayer cultures. The cells appear to revert to
      dedifferentiated chondrocytes, expressing a mesenchymal stem cell protein
      profile. Simultaneously, these cells regained their capacity to proliferate.
      Cultures held as micromass allowed reexpression of the differentiated phenotype
      traits.

PMID- 11332636
TI  - In vitro and in vivo tetracycline-controlled myogenic conversion of NIH-3T3
      cells: evidence of programmed cell death after muscle cell transplantation.
AB  - Ex vivo gene therapy of Duchenne muscular dystrophy based on autologous
      transplantation of genetically modified myoblasts is limited by their premature
      senescence. MyoD-converted fibroblasts represent an alternative source of
      myogenic cells. In this study the forced MyoD-dependent conversion of murine NIH
      3T3 fibroblasts into myoblasts under the control of an inducible promoter silent
      in the presence of tetracycline was evaluated. After tetracycline withdrawal this
      promoter drives the transcription of MyoD in the engineered fibroblasts, inducing
      their myogenesis and giving rise to beta-galactosidase-positive cells. MyoD
      expressing fibroblasts withdrew from the cell cycle, but were unable to fuse in
      vitro into multinucleated myotubes. Five days following implantation of
      engineered fibroblasts in muscles of C57BL/10J mice we observed a sevenfold
      increase of beta-galactosidase-positive regenerating myofibers in animals not
      treated with antibiotic compared with treated animals. After 1 week the number of
      positive fibers decreased and several apoptotic myonuclei were detected. Three
      weeks following implantation of MyoD-converted fibroblasts in recipient mice, no
      positive "blue" fiber was observed. Our results suggest that transactivation by
      tetracycline of MyoD may drive an in vivo myogenic conversion of NIH-3T3
      fibroblasts and that, in this experimental setting, apoptosis plays a relevant
      role in limiting the efficacy of engineered fibroblast transplantation. This work
      opens the question whether apoptotic phenomena also play a general role as
      limiting factors of cell-mediated gene therapy of inherited muscle disorders.

PMID- 11332637
TI  - Transplantation of human neural progenitor cells to the vitreous cavity of the
      Royal College of Surgeons rat.
AB  - Human neural progenitor cells, originally isolated from prenatal donor tissue at
      17 weeks of development, were cultured as neurospheres and transplanted to the
      vitreous cavity of dystrophic Royal College of Surgeons rats with, or without,
      cyclosporin A immunosuppression. Donor cells were either unlabeled or prelabeled,
      the latter utilizing incubation with BrdU or adenoviral modification to express
      green fluorescent protein. Recipients of various ages were examined at 1, 2, and
      4 weeks postgrafting. Transplanted human neural progenitor cells survived in the
      host vitreous for at least 4 weeks and maintained expression of green fluorescent
      protein for at least 2 weeks. After 2 weeks in vivo, grafted cells differentiated
      morphologically, coincident with expression of the neuronal marker MAP,
      indicating mature neuronal differentiation. The extensive intraretinal migration
      previously shown using rat progenitor cells in the Royal College of Surgeons rat
      model was not seen in this experiment, suggesting that high levels of neuronal
      migration may depend at least in part upon species-specific molecular cues. Human
      neural progenitor cells represent a renewable source of multipotent human cells
      capable of in vivo neuronal development and a potential means of delivering
      therapeutic factors intraocularly. Human neural progenitor cells therefore
      provide a useful tool for studies of neural development and differentiation in
      the dystrophic eye.

PMID- 11332638
TI  - Major mitochondrial DNA haplotype heterogeneity in highland and lowland
      Amerindian populations from Bolivia.
AB  - This study provides the frequencies of four mitochondrial DNA (mtDNA) haplogroups
      of 233 native South Amerindians in eight populations living in the Beni
      Department of Bolivia, including six populations not previously studied.
      Linguistically, these populations belong to the three principal South Amerindian
      language stocks, Andean, Equatorial-Tucanoan, and Ge-Pano-Carib. Frequency
      analyses under geographic, historic, linguistic, and genetic configurations using
      the theta statistic of Weir (Weir 1990) and analysis of molecular variance
      (AMOVA) show similar results. Results are also similar when phenetic cluster is
      used. Aymara belongs almost exclusively to haplogroup B, Quechua- and Moseten
      speaking tribes belong to haplogroups A and B, but the first tribe presents high
      frequencies of haplogroup B. Yuracare, Trinitario, and Ignaciano exhibit high
      frequencies of A, B, and C haplogroups, and the Movima present a large proportion
      of haplogroup C. There is some correspondence between mtDNA haplogroup
      frequencies and language affiliation and historical connections, but less so with
      geographic aspects. The present study provides a context for understanding the
      relationship between different Amerindian populations living in a multiethnic
      area of Bolivia.

PMID- 11332639
TI  - Polymorphic DNA haplotypes at the human low-density lipoprotein receptor gene
      locus in Koreans.
AB  - Many low-density lipoprotein (LDL) receptor mutations have been identified and
      characterized, demonstrating a high degree of allelic heterogeneity at this
      locus. The ability to identify mutant LDL-receptor genes for prenatal diagnosis
      of familial hypercholesterolemia (FH) or to study the role of the LDL-receptor
      gene in polygenic hypercholesterolemia requires the use of closely linked
      restriction fragment lenghth polymorphisms (RFLPs). In the present study nine
      different RFLPs (TaqI, StuI, HincII, BstEII, AvaII, PvuII, MspIA, MspIB, and
      NcoI) and a sequence variation at Arg450 were used to clarify the characteristics
      of the LDL-receptor gene in Koreans. A total of 978 LDL-receptor alleles from 244
      members of 43 different pedigrees (15 normal and 28 FH pedigrees) and 245
      individuals (187 normal and 58 FH) were analyzed. Frequencies of these
      polymorphisms did not differ significantly between controls and FH patients.
      Individually, seven sites--TaqI, BstEII, AvaII, MspIA, MspIB, NcoI and Arg450-
      had heterozygosity indices ranging from 0.3610 to 0.4601, whereas the PvuII site
      displayed low levels of polymorphism and StuI was monomorphic. Haplotypes were
      constructed for 215 individuals of 13 normal and 24 FH pedigrees using the nine
      polymorphisms. Of 512 (= 2(9)) possible combinations for the nine polymorphic
      sites, 39 unique haplotypes were detected. The frequency distribution of
      individual haplotypes ranged from 1/155 (0.65%) to 40/155 (25.8%). The four most
      common haplotypes accounted for 59.4% of those sampled. Statistical analysis of
      the haplotypes indicated marked linkage disequilibrium for these 10 sites and
      throughout the region containing the LDL-receptor gene. Owing to the high degree
      of linkage disequilibrium over the entire locus, not all RFLPs were informative.
      We rank each RFLP according to its informativeness and present a strategy for the
      optimal selection of RFLPs for pedigree analysis.

PMID- 11332640
TI  - Sex ratio at reproductive age: changes over the last century in the Italian
      population.
AB  - The radical improvement in living conditions experienced in Italy during the last
      century caused a reduction in male extra-mortality during the prereproductive
      years. As a consequence, a progressive increase in the sex ratio at the beginning
      of the reproductive age (15-19 years) occurred, so that in recent times the sex
      ratio in the young adult population has approached the almost constant value of
      1.06 observed at birth. We calculated that the sex composition would be the same
      in newborns and in young adults in about one generation: obviously, we have to
      assume that the sex differentials in mortality and migration are constant over
      time. The 1:1 equilibrium between sexes, which maximizes reproductive success,
      occurred in the 15-19 age group at the beginning of the century and shifted to
      the 30-35 age group in the 1990s. We compared the 1993-1995 sex ratios in
      different age groups in European Union countries and observed that in Italy as
      well as in other Mediterranean countries the numerical equality between sexes is
      reached at 30-35 years of age, while in north-central Europe it is reached later,
      approximately at the end of reproductive life.

PMID- 11332641
TI  - Geographical north-south decline in DNASE1*2 in Japanese populations.
AB  - Allele frequencies for human deoxyribonuclease I (DNase I) phenotypes were
      determined using blood samples from about 2000 Japanese subjects living in nine
      prefectures, and compared with one another. DNase I phenotyping was performed
      principally using isoelectric focusing electrophoresis and activity staining. The
      DNase I system was shown to have enhanced potential for anthropologic, genetic,
      and clinical studies of Japanese populations. DNase I phenotypes were analyzed to
      evaluate the degree of genetic variation at the DNASE1 locus. Our examination of
      DNase I types revealed a decreasing north-to-south gradient in the DNASE1 allele.

PMID- 11332642
TI  - APOE polymorphism in a rural older population-based sample in India.
AB  - Allele frequencies are most often reported from small convenience samples of
      unknown demographics and limited generalizability. We determined the distribution
      of apolipoprotein E genotype (APOE) and allele frequencies for a large, well
      defined, representative, rural, population-based sample (n = 4450) aged 55-95
      years in Ballabgarh, in the northern Indian state of Haryana. The overall APOE
      E*2, E*3, and E*4 allele frequencies were 0.039, 0.887, and 0.073, respectively;
      frequencies are also reported by age, sex, and religious/caste groups. The APOE*4
      frequency is among the lowest reported anywhere in the world. APOE allele
      frequencies did not vary significantly by age or sex in this study. To our
      knowledge, this is the largest Indian sample ever genotyped for the APOE
      polymorphism. The representativeness of the sample and its known demographics
      provide a much-needed normative background for studies of gene-disease
      associations.

PMID- 11332643
TI  - Hemochromatosis gene variants in three different ethnic populations: effects of
      admixture for screening programs.
AB  - Genetic testing for hemochromatosis may have important implications for diagnosis
      and screening of the disease. However, the relative importance of mutations in
      the gene for hereditary hemochromatosis, HFE, may vary among populations, when
      the mutant allele frequencies and their penetrance in a particular genetic and
      environmental background are taken into account. We present data on the allele
      and genotype frequencies and population structure of two HFE genetic variants in
      three different ethnic groups from a highly mixed urban population (Sao Paulo,
      Brazil). Allele frequencies for both the C282Y and H63D HFE mutations showed
      significant differences among the studied populations (for the C282Y mutation,
      Euro-Brazilian 3.7%, admixed 0.7%, Afro-Brazilian 0.5%; and for the H63D
      mutation, Euro-Brazilian 20.3%, admixed 13.0%, Afro-Brazilian 6.4). The data
      substantiate a European origin for these mutations. Furthermore, they provide a
      basis for a more rational strategic planning of population screening programs for
      the disease.

PMID- 11332644
TI  - Distribution of mitochondrial DNA lineages among Native American tribes of
      Northeastern North America.
AB  - The mtDNA haplogroups of 185 individuals from Native American tribes in Northeast
      North America were determined. A subset of these individuals was analyzed by
      sequencing hypervariable segments I and II of the control region. The haplogroup
      frequency distributions of populations in the Northeast exhibit regional
      continuity that predates European contact. A large amount of gene flow has
      occurred between Siouan-and Algonquian-speaking groups, probably due to an
      Algonquian intrusion into the Northeast. The data also support both the Macro
      Siouan hypothesis and a relatively recent intrusion of Northern Iroquoians into
      the Northeast. These conclusions are consistent with archaeological and
      linguistic evidence.

PMID- 11332645
TI  - R-matrix analysis and patterns of gene flow in India.
AB  - An appraisal on the usefulness of R-matrix analysis and the model of Harpending
      and Ward (1982) to study the population structure of Indian populations is made
      in the light of prevalent marriage patterns, caste structure, and cultural
      specificity of the region. With the help of available data on the migration
      histories and geographical backgrounds of marine fishermen on the east coast of
      India, and through the historical analysis of marriage patterns, it is
      demonstrated that the routine inferences based on the regression plots of average
      heterozygosity versus genetic distance from the centroid may not generally be apt
      for the Indian situation. Increased heterozygosity among migrant fishermen seems
      to have resulted from mating patterns within this community rather than from
      external gene flow. In either case, the genetic implications are supposedly
      identical. Nevertheless, when making inferences regarding local population
      structure it is important to have detailed knowledge of mating patterns and the
      cultural context of the region under study.

PMID- 11332646
TI  - The SRY-1532 site of the human Y chromosome is subject to recurrent single
      nucleotide mutations.
AB  - Haplotype determination based on three Y-linked polymorphic sites, 92R7 (C/T),
      SRY-1532 (A/G), and YAP (-/+), in 127 males belonging to three caste Hindu
      populations of South India (Vizag Brahmins, Peruru Brahmins, and Kammas) and 13
      males belonging to a migrant group (the Siddis) showed the existence of all four
      haplotypes (CA-, CG-, TG-, and TA-) under the YAP- background. This finding
      suggests that the reverse mutation (G-->A) at the SRY-1532 site, described
      earlier in the literature, is present in South Indian populations as well. The
      YAP+ mutation was seen in only five Siddi individuals. Four of these were of the
      CG+ haplotype structure, but a novel haplotype (CA+) was found in one male. To
      explain the occurrence of the six haplotypes found within these three sites, a
      haplotype tree is constructed that introduces a new reverse mutation at the SRY
      1532 site (G-->A), occurring under the CG+ background after the migrant Siddi
      population arrived in India.

PMID- 11332647
TI  - Evidence of a sex-dependent association between the MSX1 locus and nonsyndromic
      cleft lip with or without cleft palate in the Chilean population.
AB  - Prior studies have implicated an involvement of the Msx1 homeobox gene in cleft
      palate in mice and its homolog in humans (called MSX1 in the HOX7 gene, located
      on chromosome 4). In this study we present evidence of a sex-dependent
      association between MSX1 and non-syndromic cleft lip/palate (NSCLP) in the
      Chilean population. The sample included 73 NSCLP cases, 37 from multiplex
      families (Mx), 36 from simplex families (Sx), and 87 controls. Polymerase chain
      reaction amplification of the MSX1 intragenic microsatellite (CA)n-sequence shows
      significant (p = 0.035) differences in the allele frequencies between NSCLP-Mx
      males and control males. These differences are mainly due to frequency
      differences in allele *2 (173 base pairs) among cases (21.9%) and controls
      (13.2%). When the NSCLP cases are subdivided by sex and positive family history
      (Mx versus Sx), the Mx males (27.8%) as well as the total NSCLP-Mx cases (25.7%)
      showed significantly higher frequencies of allele *2, compared to controls (11.4%
      and 13.2%, respectively). Analysis of the genotype data indicates that the
      relative risk for NSCLP is greater for persons carrying allele *2 (i.e., odds
      ratio [OR] larger than 1), reaching significance for all Mx cases (OR = 2.67; 95%
      confidence interval [CI], 1.10 to 6.52) and even more pronounced for Mx males (OR
      = 3.33; 95% CI, 1.08 to 10.32). Taken together, these findings support the
      hypothesis that the genetic variation at the MSX1 locus is a predisposing gene
      involved in sex-dependent susceptibility to clefting and that it also
      differentiates simplex from multiplex families.

PMID- 11332648
TI  - Genetic effect of two APOA repeat polymorphisms (kringle 4 and pentanucleotide
      repeats) on plasma Lp(a) levels in American Samoans.
AB  - Elevated plasma lipoprotein(a) [Lp(a)] level has been established as an
      independent risk factor for atherosclerosis and coronary heart disease.
      Considerable ethnic group differences in the distribution of plasma Lp(a) levels
      have raised public health concerns. Recently, we have reported that Samoans have
      the lowest plasma Lp(a) levels of any population group. In the present
      investigation, we report the contribution of two apolipoprotein(a) (APOA)
      polymorphisms, the kringle 4 type 2 (K4) repeat and the pentanucleotide repeat
      (PNR), in affecting plasma Lp(a) levels in an American Samoan sample (n = 309).
      The K4 repeats ranged in size from 15 to 40. The common alleles contained repeats
      ranging from 26 to 36 with allele frequencies between 5.5% to 9.7%, and these
      accounted for 82% of all alleles. An inverse relationship between K4 repeat
      number and plasma Lp(a) level was observed for single-banded (r = -0.59, p =
      0.0001) and double-banded phenotypes (r = -0.50, p = 0.0001). This polymorphism
      explained 60% of the variation in plasma Lp(a) level in American Samoans. For the
      PNR polymorphism, five different repeat alleles and eight different genotypes
      were identified; the most common allele was eight repeats. The *8 PNR allele was
      associated with a wide range of K4 repeats, the *9 PNR allele with larger K4
      repeats (25-40), and the *10 PNR with smaller K4 repeats (15-24). Analysis of
      variance (ANOVA) revealed that the PNR polymorphism accounts for 2.1% of the
      variability in plasma Lp(a) levels in this sample, when the K4 repeat
      polymorphism was taken into account. Our data show that common polymorphisms in
      the APOA gene are major determinants of plasma Lp(a) variation in American
      Samoans.

PMID- 11332649
TI  - Impact of age on hypermutation of immunoglobulin variable genes in humans.
AB  - Chronological aging is associated with an accumulation of DNA mutations that
      results in cancer formation. The effect of aging on spontaneous mutations in
      humans is difficult to study because mutations are infrequent in the overall
      genome and tumors are relatively rare. In contrast, somatic mutations in
      immunoglobulin variable genes are abundant and can be studied in peripheral blood
      lymphocytes. To determine if aging alters the frequency and pattern of
      hypermutation, we sequenced 331 cDNA clones with rearranged V(H)6 genes and
      compared 452 mutations from young humans to 570 mutations from old humans. There
      were more mutated clones in the young population compared to the old population.
      Among the mutated clones, the frequency, location, and types of substitutions
      were similar between the young and the old groups. However, the ratio of
      replacement-to-silent mutations was much higher in the complementarity
      determining regions of heavy chains from old people, which indicates that their B
      cells had been selected by antigen. Among individuals, there was variability in
      the frequency of tandem mutations, which we have observed in mice defective for
      the PMS2 mismatch repair protein. Microsatellite variability in DNA, which is
      caused by impaired mismatch repair, was then measured, and there was a strong
      correlation between the frequency of tandem mutations and microsatellite
      alterations. The data suggest that individuals vary in their mismatch repair
      capacity, which can affect the mutational spectra in their antibodies.

PMID- 11332650
TI  - IL-12 as well as IL-2 upregulates CCR5 expression on T cell receptor-triggered
      human CD4+ and CD8+ T cells.
AB  - The expression of chemokine receptors on leukocytes is related to their
      activation state. However, the exact mechanism underlying the induction of each
      chemokine receptor is poorly understood. Here, we investigated how CCR5, a
      chemokine receptor implicated in T cell trafficking and HIV infection, is induced
      in human T cells. CCR5 was marginally detected on a freshly prepared human
      peripheral blood mononuclear cell (PBMC) population. Long-term (8-day)
      stimulation of PBMC with IL-2 resulted in high levels of CCR5 expression on T
      cells. IL-12 failed to induce CCR5 on T cells in such a directly stimulated PBMC
      population. Stimulation of PBMC T cells with anti-CD3 plus anti-CD28 induced
      detectable albeit very low levels of CCR5 along with the induction of IL-12
      receptor. However, these TCR-triggered T cells expressed much higher levels of
      CCR5 when stimulated with IL-12. Although IL-2 also induced CCR5 expression, CCR5
      expression was more potent in IL-12 than IL-2 stimulation. These results indicate
      that, in addition to IL-2, IL-12 plays an important role in the induction of CCR5
      expression on T cells, particularly TCR-triggered T cells.

PMID- 11332651
TI  - Prevalence of an ulcerative colitis-associated CD8+ T cell receptor beta-chain
      CDR3-region motif and its association with disease activity.
AB  - The normal human intestinal mucosa contains clonal T cell expansions. Clonal
      populations of T cells can be determined through evaluation of the idiotypic,
      hypervariable region of their T cell receptor (TCR). We have previously reported
      that there exists a highly conserved TCR pattern among intestinal CD8+ T cells in
      the majority of ulcerative colitis (UC) patients undergoing colectomy that was
      not present in normal control individuals. This TCR pattern, or motif, was
      characterized by particular beta-chain usage (TCRBV3 and TCRBJ1S6) and a defined
      length in the hypervariable third complementarity determining region (CDR3). The
      aim of this study was to assess the motif's relationship to disease activity.
      Subjects were 66 with UC, 19 with Crohn's disease, 14 inflammatory controls, and
      6 normal controls. cDNA and gDNA were prepared from colonic biopsies and paraffin
      blocks, respectively, obtained from study subjects and used to assess TCRBV CDR3
      region length and usage, as well as for cloning and sequencing of TCRs. The TCRBV
      CDR3 region was present in 25 of a series of 48 UC subjects but only 3 of 19
      Crohn's disease patients and 3 of 14 inflammatory controls. The motif was more
      common in UC than either Crohn' s disease or inflammatory controls (chi2 = 7.5, P
      = 0.006, and chi2 = 4.1, P = 0.04, respectively). The motifs presence was not
      dependent upon histologic disease activity (either active or inactive UC).
      Clinical UC disease activity was also not significantly associated with an
      increased presence of the motif in 14 paired biopsies, which were taken during
      times of clinical activity or inactivity. There was a trend toward persistence of
      the motif, as it was present in 6 of 14 subjects over a 3- to 6-month time
      period. The previously described UC-associated TCRBV CDR3 region motif located in
      the intestinal CD8+ T-cell subset is found in a significant proportion of UC
      subjects. The TCR motif does not significantly discriminate active from inactive
      disease states. The persistent and diffuse nature of this TCR-associated motif in
      UC suggests that an ongoing T-cell response to a particular antigen(s) is
      occuring in this disorder.

PMID- 11332652
TI  - Enhanced interferon-gamma by CD8+ CD28- lymphocytes from HIV+ patients.
AB  - Flow cytometric analysis of T cells from HIV+ and normal individuals activated
      for 15 hr showed that the percentage of cells producing interferon-gamma
      (INFgamma) was enhanced approximately threefold (39 compared to 14%) in the HIV+
      CD8+ population. Activation modes, other than anti-CD3 with PMA, were
      ineffective, and in no case did the percentage of HIV+ CD4+ T cells show
      increased INFgamma production over controls. Enhanced INFgamma production was not
      induced by either anti-CD3 or PMA alone, or anti-CD3 or ConA with anti-CD28, or
      enhanced by N-acetylcysteine. In contrast to INFgamma production, the percentage
      of CD4+ T cells producing interleukin-2 (Il-2) greatly exceeded that of the CD8+
      T cells. The results from flow cytometry analyses of HIV+ CD8+ T cells was
      supported by quantitative analysis of INFgamma mRNA (by PCR) and INFgamma
      secretion by ELISA. These methods showed a sixfold and three- to fivefold
      increase, respectively, on a per cell basis. As HIV infection progresses, as
      shown by loss of CD4+ T cells, the proportion of CD8+ CD28- T cells increases,
      and it is this T cell subset that is responsible for 80% or more of the enhanced
      INFgamma production. The enhanced INFgamma in HIV+ patients derives from two
      factors: the increase in CD8+ CD28- cells to 70% and the percentage producing
      INFgamma (60%, compared to 21% for CD8+ CD28+ cells). Our findings of a
      substantial increase in INFgamma production in HIV infection arising from the
      increased number of CD8+ CD28- T cells are compatible with clinical studies which
      show elevated INFgamma in HIV+ serum and INFgamma producing CD8+ T cells
      dominating HIV+ lymph nodes. We also found a significantly decreased
      proliferative response of the HIV+-derived CD8+ T cell fraction with coactivator
      anti-CD-28, in contrast to PMA (with anti-CD3), which is probably a reflection of
      the diminished population of CD8+ CD28+ T cells in HIV+ donors compared to normal
      donors (30.7 compared to 67.9%).

PMID- 11332653
TI  - Diagnostic findings in 95 Finnish patients with common variable immunodeficiency.
AB  - Common variable immunodeficiency is the most frequent of the primary
      hypogammaglobulinemias. It is manifested by a wide variety of clinical signs and
      symptoms. In this retrospective, nationwide survey data were collected on all
      patients with common variable immunodeficiency who were receiving immunoglobulin
      replacement therapy in Finland to study the prediagnostic clinical picture,
      diagnostic delay, and diagnostic findings. Ninety-five patients were identified.
      The median age of the patients was 33 years. Sixteen of the patients were
      children. Sinopulmonary infections were the most common prediagnostic signs and
      symptoms; 66% had suffered from recurrent pneumonia, 60% from recurrent maxillary
      sinusitis, and 45% from recurrent bronchitis. There was a considerable delay in
      diagnosis. The mean delay was 8 years. At the time of diagnosis chronic pulmonary
      complications had already developed in 17% of the patients. The diagnosis was
      based on low serum immunoglobulin concentrations. This study showed that the
      awareness of common variable immunodeficiency is low. To improve the recognition
      of hypogammaglobulinemia, it should be suspected in every patient with recurrent
      bacterial infections. In addition to a low serum IgG concentration, measurement
      of specific antibody production is recommended to establish the diagnosis before
      initiation of a life-long and costly replacement therapy.

PMID- 11332654
TI  - Rapid subcutaneous IgG replacement therapy at home for pregnant immunodeficient
      women.
AB  - The use of slow or rapid, subcutaneous, IgG (SCIG) infusions in pregnant women
      with primary antibody deficiencies has been described earlier, though only in
      single-case reports. In this study, we have evaluated the effect of rapid, SCIG
      infusions during 11 pregnancies in nine women [six women with common variable
      immunodeficiency (CVID), two with IgG-subclass deficiencies, and one with
      combined IgA and IgG2 deficiency]. The weekly infusions were given by the women
      themselves at a dose of 100 mg/kg/week throughout the pregnancy. No adverse
      systemic reactions or pronounced, local tissue reactions were recorded during or
      after the more than 400 infusions. The 11 babies were healthy and were born after
      38-42 weeks of uneventful gestation. The concentrations of maternal S-IgG at the
      time of delivery in the four women with CVID ranged from 6.0 to 8.3 g/L, with
      cord/maternal S-IgG ratios of 1.0-1.5. The IgG subclasses were transferred to the
      infants. The SCIG home-therapy regime was greatly appreciated by the women.

PMID- 11332655
TI  - Autonomic regulation of neuroimmunological responses: implications for multiple
      sclerosis.
AB  - The expression of neural regulatory molecules by immune cells that infiltrate the
      nervous system upon injury may be a mechanism for cross regulation between the
      nervous system and the immune system. Several lines of evidence implicate nerve
      growth factor signaling through its receptors as a potential source of
      communication between the two systems. The expression of beta-adrenergic
      receptors and sympathetic innervation of lymphoid organs represents another
      example of communication between the immune and the nervous system. In this
      review, we discuss mechanisms of how factors in common between the nervous system
      and the immune system may result in regulatory circuits which are important in
      both healthy and diseased states. These studies may have relevance for a number
      of inflammatory conditions in humans, including multiple sclerosis.

PMID- 11332656
TI  - The origin and regulation of autopathogenic T cells.
AB  - A clear understanding of the events surrounding the selection of autoreactive T
      cells in the thymus and their regulation in the periphery has eluded
      immunologists for years. However, recent work examining the expression of tissue
      specific antigens in the thymus and the biochemistry of disease associated MHC
      alleles has provided important clues into the generation of the autoreactive T
      cell repertoire in the thymus. In addition, recent studies focusing on the role
      of immunoregulatory cytokines and cross-reactive peptide ligands has provided
      information regarding both the regulation and activation of autoreactive cells in
      the periphery. An improved understanding of the selection and regulation of
      autoreactive T cells will undoubtedly aid in the development of strategies for
      treating autoimmune disease.

PMID- 11332658
TI  - Antigen specific immunotherapy of multiple sclerosis.
AB  - The development of antigen specific therapy for multiple sclerosis (MS) involves
      specifically suppressing undesired immune responses targeting the myelin sheath
      and underlying axon. We have recently reported some success with altered peptide
      ligands for a major target of the autoimmune response in MS. Antigen specific
      therapy has the potential to suppress undesirable autoimmunity, while leaving the
      rest of the immune system intact. Induction of an antigen specific Th1-to-Th2
      shift could achieve this aim, once side effects, such as allergic responses, are
      minimized with optimal dosing.

PMID- 11332659
TI  - The importance of omega-3 fatty acids in the attenuation of immune-mediated
      diseases.

PMID- 11332660
TI  - Failure of rifampin to eradicate group B streptococcal colonization in infants.
AB  - BACKGROUND: Mucous membrane colonization with group B streptococci (GBS)
      frequently persists in infants after treatment of invasive infection and may be
      associated with recurrent disease. OBJECTIVE: To determine the frequency with
      which GBS colonization persists at mucous membrane sites after treatment of
      invasive early or late onset infection and to determine the efficacy of oral
      rifampin in eradicating colonization in these infants and their mothers. METHODS:
      Cultures for isolation of GBS were obtained from infants and their mothers after
      completion of the infant's parenteral therapy, 1 week later when rifampin therapy
      was initiated and at approximately 1 and 4 weeks after completion of rifampin
      therapy. Rifampin was administered (10-mg/kg dose; maximum, 600 mg) twice daily
      for 4 days. RESULTS: Ten of 21 infants (48%) and 13 (65%) of their 20 mothers
      were colonized with GBS at throat or rectal (infant) or vaginal, rectal or breast
      milk (mother) sites before rifampin was initiated. One week or less after
      rifampin treatment, 7 (70%) infants and 4 (31%) mothers remained colonized with
      GBS. At study completion 6 infants and 7 mothers had GBS colonization. Persistent
      colonization was not related to GBS serotype, to initial rifampin minimal
      inhibitory concentration or to the development of rifampin resistant strains.
      CONCLUSIONS: Rifampin treatment for four days utilized as a single agent after
      completion of parenteral therapy failed to reliably eradicate GBS colonization in
      infants.

PMID- 11332657
TI  - The neuroimmunology of multiple sclerosis: possible roles of T and B lymphocytes
      in immunopathogenesis.
AB  - Multiple sclerosis (MS) is an inflammatory disease of the central nervous system
      white matter. The association of the disease with MHC genes, the inflammatory
      white matter infiltrates, similarities with animal models, and the observation
      that MS can be treated with immunomodulatory and immunosuppressive therapies
      support the hypothesis that autoimmunity plays a major role in the disease
      pathology. Evidence supports activated CD4+ myelin-reactive T cells as major
      mediators of the disease. In addition, a renewed interest in the possible
      contribution of B cells to MS immunopathology has been sparked by nonhuman
      primate and MS pathological studies. This review focuses on the immunopathology
      of MS, outlining the hypothetical steps of tolerance breakdown and the molecules
      that play a role in the migration of autoreactive cells to the CNS. Particular
      focus is given to autoreactive T cells and cytokines as well as B cells and
      autoantibodies and their role in CNS pathogenesis in MS.

PMID- 11332661
TI  - Acute mastoiditis in children: a seventeen-year experience in Dallas, Texas.
AB  - BACKGROUND: In the preantibiotic era acute mastoiditis was the most common
      complication of acute otitis media, often resulting in substantial morbidity and
      mortality. Since 1989 several investigators have documented an increased
      frequency of acute mastoiditis in children. METHODS: The medical records of all
      children with a discharge diagnosis of acute mastoiditis, managed at Children's
      Medical Center, Dallas, TX, from 1983 through 1999 were reviewed. RESULTS: There
      were 57 cases of acute mastoiditis during the 17-year period of 1983 through 1999
      compared with 57 cases in a 25-year period of 1955 through 1979 reported
      previously at the same institution. The number of cases of acute mastoiditis per
      10,000 hospital admissions increased significantly (regression analysis P =
      0.003) during the more recent 17 years. From 1993 through 1999 there were 4.5
      cases or more per 10,000 admissions each year, whereas from 1983 through 1992,
      the incidence never exceeded 4.3 cases per 10,000 admissions (P = 0.018). The
      median age of the patients was 48 months. Twenty-two patients (38.5%) were
      younger than 24 months; 17 of these were 12 months of age or younger. Twenty-two
      (38.5%) patients had no history of previous episodes of acute otitis media.
      Streptococcus pneumoniae was the pathogen most often isolated from the cultures.
      Complications of mastoiditis occurred in 20 children (35%). CONCLUSIONS: We
      conclude that acute mastoiditis continues to be a problem in the post antibiotic
      era. It occurs mainly in young children and can be the first evidence of ear
      disease.

PMID- 11332662
TI  - Evidence base of incubation periods, periods of infectiousness and exclusion
      policies for the control of communicable diseases in schools and preschools.
AB  - BACKGROUND: The optimal control of communicable diseases requires accurate
      information on incubation periods, periods of infectiousness and the
      effectiveness of exclusion. We collected the available evidence for a wide range
      of infections and infestations and produced evidence-based guidelines for their
      control in schools and preschools. METHODS: A thorough MEDLINE literature search
      was conducted on the incubation period, period of infectiousness and
      effectiveness of exclusion for 41 infections. The quality of the information
      obtained was indicated by levels of evidence. The information was used to produce
      guidelines on exclusion, and the recommendations were graded according to the
      levels of evidence available. Grades A, B and C represented strongly, reasonably
      and poorly evidence-based recommendations, respectively. RESULTS: The quality of
      data obtained was highly variable. Information on incubation periods was obtained
      for all 41 infections and was generally of good quality. Information on periods
      of infectiousness and effectiveness of exclusion was of a lesser quality and was
      found for only 11 and 4 conditions, respectively. There were 3 Grade A, 17 Grade
      B and 21 Grade C recommendations on exclusion. Examples of exclusion periods
      include: 5 days for chickenpox, measles, mumps, rubella, pertussis and scarlet
      fever; and 24 h from the cessation of diarrhea for most gastrointestinal diseases
      In contrast to existing guidelines exclusion was not recommended for school age
      children with hepatitis A. CONCLUSIONS: We have been able to present the best
      available data on the incubation periods and periods of infectiousness of 41
      childhood infections. It was possible to produce strongly or reasonably evidence
      based guidelines on exclusion periods for approximately one-half of the
      infections.

PMID- 11332663
TI  - Outcome of invasive infections outside the central nervous system caused by
      Streptococcus pneumoniae isolates nonsusceptible to ceftriazone in children
      treated with beta-lactam antibiotics.
AB  - OBJECTIVE: To determine the outcome of children treated primarily with beta
      lactam antibiotics for a systemic infection outside the central nervous system
      (CNS) caused by isolates of Streptococcus pneumoniae nonsusceptible to
      ceftriaxone (MIC > or = 1.0 microg/ml). DESIGN: Retrospective review of the
      medical records of children identified prospectively with invasive infections
      outside of the CNS caused by isolates of S. pneumoniae that were not susceptible
      to ceftriaxone between September, 1993, and August, 1999. A subset of this group
      treated primarily with beta-lactam antibiotics was analyzed for outcome.
      PATIENTS: Infants and children with pneumococcal infections cared for at eight
      children's hospitals. RESULTS: Among 2,100 patients with invasive infections
      outside the CNS caused by S. pneumoniae, 166 had isolates not susceptible to
      ceftriaxone. One hundred patients treated primarily with beta-lactam antibiotics
      were identified. From this group 71 and 14 children had bacteremia alone or with
      pneumonia, respectively, caused by strains with an MIC of 1.0 microg/ml.
      Bacteremia or pneumonia caused by isolates with a ceftriaxone MIC > or = 2.0
      microg/ml occurred in 6 and 5 children, respectively. Three children with septic
      arthritis and 1 with cellulitis had infections caused by strains with an MIC to
      ceftriaxone of 1.0 microg/ml. Most were treated with parenteral ceftriaxone,
      cefotaxime or cefuroxime for one or more doses followed by an oral antibiotic.
      All but one child were successfully treated. The failure occurred in a child with
      severe combined immune deficiency and bacteremia (MIC = 1.0 microg/ml) who
      remained febrile after a single dose of ceftriaxone followed by 12 days of
      cefprozil. CONCLUSION: Ceftriaxone, cefotaxime or cefuroxime are adequate to
      treat invasive infections outside the CNS caused by pneumococcal isolates with
      MICs up to 2.0 microg/ml, a concentration currently considered resistant for
      these antibiotics by National Committee for Clinical Laboratory Standards
      breakpoints.

PMID- 11332664
TI  - Lymphocyte subsets in human immunodeficiency virus type 1-infected and uninfected
      children in Nairobi.
AB  - BACKGROUND: Reference lymphocyte subset values for African children are lacking.
      This study documents these values as well as their alterations associated with
      perinatal and postnatal HIV-1 transmission and with protection from HIV-1
      infection. METHODS: Lymphocyte subsets were determined for HIV-1-seronegative
      nonpregnant women and their children (controls) and for uninfected, perinatally
      infected and postnatally infected children born to HIV-1-seropositive mothers in
      Nairobi, Kenya. The mean, median and 5th and 95th percentile values for CD4+ and
      CD8+ lymphocyte counts and percentages were determined and compared at the age
      ranges birth to 3 months, 4 months to 1 year, yearly from 1 to 5 years and from 6
      to 10 years of age. RESULTS: Among control children counts differed from
      published values of other populations. In all age ranges, whereas the absolute
      values were significantly higher than adult values, the percentages were
      significantly lower. Children perinatally infected with HIV-1 had clearly
      distinguishable differences in lymphocyte subset percentages by 3 months of age,
      when the median CD4+ percentage was 27.9% (5th to 95th percentile, 25.7 to 30.1%)
      for infected vs. 35.9% (33.3 to 38.7%) for uninfected and 39.9% (37.8 to 42.2%)
      for control children, P < 0.001; whereas the median CD8+ percentage was 37.0%
      (33.1 to 41.0%) for infected vs. 27.5% (24.2 to 30.8%) for uninfected and 27.5%
      (24.2 to 30.8%) for control children, P = 0.001. Differences between uninfected
      and control children disappeared after 1 year of age. CONCLUSIONS: Normal
      lymphocyte subset values among African children differ from those in other
      populations. Significant differences are detectable by 3 months of age in CD4+
      and CD8+ lymphocyte percentages among perinatally infected infants, which may be
      useful as an adjunct in diagnosis. Transient differences observed among HIV-1
      exposed but uninfected infants could reflect a successful immune response to HIV
      1 challenge.

PMID- 11332666
TI  - Population-based study of rotavirus vaccination and intussusception.
AB  - BACKGROUND: During the first year that the rhesus rotavirus tetravalent vaccine
      (RRV-TV) was licensed, the Vaccine Adverse Event Reporting System received
      several reports of intussusception after vaccination. To evaluate the risk of
      intussusception, we conducted a retrospective cohort study in ten managed care
      organizations. METHODS: Cases of intussusception were identified by searching
      electronic databases for diagnoses of intussusception (ICD-9 Code 560.0) in
      infants 1 to 11 months of age and confirmed by medical chart review. Vaccination
      and enrollment data were obtained from administrative databases. Incidence rate
      ratios (RR) of intussusception were computed by dividing incidence rates in
      prespecified risk intervals after vaccination by the background rate of
      intussusception and adjusted for age by Poisson regression. Cox proportional
      hazard regression was used to evaluate risk by vaccine dose. RESULTS: Of 463,277
      children 56,253 had been vaccinated with a total of 91 371 doses of RRV-TV. The
      incidence rate of intussusception was 25/100,000 person years among unexposed
      infants and 340/100,000 person years 3 to 7 days postvaccination. In the interval
      3 to 7 days after vaccination, the age-adjusted RR was 16.0 (95% confidence
      interval, 5.5 to 46.7) for all doses combined and 30.4 (95% confidence interval,
      8.8 to 104.9) after the first dose. RRs for the 8- to 14- and 15- to 21-day risk
      intervals were >1.0, but the confidence intervals substantially overlapped 1.0.
      The attributable risk was one case of intussusception per 11 073 children
      vaccinated. CONCLUSIONS: RRV-TV is associated with an increased risk of
      intussusception. The risk is greatest 3 to 7 days after the first vaccination
      dose.

PMID- 11332665
TI  - Severe, rapidly progressive human immunodeficiency virus type 1 disease in
      newborns with coinfections.
AB  - AIM: To describe a severe form of rapidly progressive HIV-1 infection manifesting
      in the neonatal period. METHOD: Prospective cohort study, King Edward VIII
      Hospital, Durban, South Africa. HIV-1-exposed neonates with hepatosplenomegaly,
      lymphadenopathy or persistent pneumonia within the first 28 days of life were
      investigated for perinatal infections. Confirmation of neonatal HIV-1 infection,
      HIV-1 subtype and clinical outcomes were studied. RESULTS: Twenty-three (72%) of
      32 symptomatic HIV-1-exposed neonates recruited at a mean of 15.2 days were HIV-1
      infected. HIV-1 infection was detected in 5 patients who were tested within 48 h
      of birth, confirming congenital infection. Congenital infection was not excluded
      in any case. Median neonatal viral load at recruitment was 471,932 copies/ml and
      median CD4 was 777 cells/mm3. The predominant clinical presentation was growth
      retardation and prematurity. Perinatal infections detected included: tuberculosis
      (8), syphilis (6) and cytomegalovirus (10). All of the neonates with perinatal
      tuberculosis were HIV-1-coinfected. Maternal and neonatal viral load and CD4 at
      recruitment were not statistically different between the groups with tuberculosis
      vs. other coinfections. Gag gene sequence analysis confirmed closely aligned HIV
      1 subtype C in mothers and neonates. Nineteen (83%) died by 9 months, with a mean
      age at death of 3.5 months. CONCLUSIONS: A distinct group of HIV-1-infected
      babies may clinically manifest in the neonatal period with perinatal
      coinfections, subsequent rapidly progressive HIV-1 and early death.

PMID- 11332667
TI  - Three-year survey of bacteremia and fungemia in a pediatric intensive care unit.
AB  - BACKGROUND: Knowledge of the pattern of blood stream infection (BSI) in patients
      in intensive care units (ICUs) can help determine antibiotic prescribing policy
      and infection control procedures. However, there have been few pediatric-based
      studies. METHODS: Surveillance of BSI in a pediatric ICU for 3 years, amounting
      to 131 episodes of significant bacteremia and fungemia. RESULTS: The incidence of
      BSI was 39.0 per 1,000 admissions (10.6 per 1,000 bed days). Eighty-four (64.1%)
      episodes were ICU-acquired, and 27 (20.6%) were community-acquired. Gram
      positive, Gram-negative and anaerobic bacteria accounted for 62.2, 30.8 and 1.4%,
      respectively, of the 143 microorganisms isolated, 5.6% were yeasts. Neisseria
      meningitidis was the most common species in community-acquired infections, and
      staphylococci predominated in hospital-acquired episodes. Eighty-seven percent of
      patients had significant underlying disease, including 60.3% with congenitally
      acquired conditions. Intravascular devices were the most common source of
      infection, accounting for 41.2% of all episodes. The crude mortality in children
      with BSI was 26.5%, compared with 8.1% in those without BSI. CONCLUSIONS: The
      pattern of BSI in ICUs is partly determined by the type of patient treated.
      However, some observations are generally applicable, notably the increasing
      importance of antibiotic-resistant bacteria that are often of low virulence and
      device-associated. Our experience suggests that universal use of broad spectrum
      empiric antibiotics to cover these pathogens (which risks further promoting
      antibiotic resistance) may not improve patient outcome. Our study provides a
      basis for other pediatric ICUs to evaluate their rates and outcomes of BSI.

PMID- 11332668
TI  - Demographic rather than behavioral risk factors predict herpes simplex virus type
      2 infection in sexually active adolescents.
AB  - BACKGROUND: Despite the high prevalence of herpes simplex virus type 2 (HSV-2)
      infection in adults and data indicating that many HSV-2 infections are acquired
      in late adolescence, the demographic and sexual behavior correlates of HSV-2
      infection in high risk adolescents have not been extensively studied. METHODS:
      Using a cross-sectional design we evaluated serologic evidence of HSV-2 infection
      in 381 adolescents age 14 to 19 years at an urban sexually transmitted disease
      clinic and a community clinic. Study enrollment was offered to all patients
      participating in a project offering free hepatitis B vaccine. Participants were
      interviewed and blood was drawn for HSV Western blot. RESULTS: Twelve percent
      [95% confidence interval (CI), 8.6 to 15.1] of 379 adolescents in this study had
      antibodies to HSV-2. Only 22% of HSV-2-seropositive youth reported a history of
      herpes. Seropositivity for HSV-2 was significantly associated with African
      American race (odds ratio, 2.3; 95% CI 1.1 to 4.8) and female gender (odds ratio,
      6.0; 95% CI 2.3 to 15.9); 25% of the African-American girls were HSV-2
      seropositive. Self-reported condom use, number of sexual partners in the prior 2
      months and history of a sexually transmitted disease did not predict HSV-2
      antibody status. CONCLUSIONS: HSV-2 infection among adolescents was prevalent,
      particularly among African-American girls, and correlated with demographic rather
      than behavioral variables. As in adults most HSV-2 infections were unrecognized.
      These data suggest that type-specific serologic testing for HSV-2 infection
      should be considered in sexually active adolescents. Prevention efforts should
      target children before initiation of sexual activity.

PMID- 11332669
TI  - Fifth vaccination with dipthteria, tetanus and acellular pertussis is beneficial
      in four- to six-year-olds.
AB  - OBJECTIVE: Diphtheria, tetanus and pertussis serum antibody titers were assessed
      before a fifth dose of diphtheria-tetanus-acellular pertussis (DTaP) or
      diphtheria-tetanus-whole cell pertussis (DTwP) vaccination at age 4 to 6 years.
      METHODS: Healthy children who had participated in a series of National Institutes
      of Health-sponsored trials assessing DTwP and DTaP vaccines provided
      prevaccination sera before a fifth dose of DTwP or DTaP. The trial design was
      prospective, randomized and double blind. Diphtheria, tetanus and pertussis
      antibody titers were measured by enzyme-linked immunosorbent assay. Pertussis
      results are expressed in enzyme-linked immunosorbent assay units/ml based on US
      Food and Drug Administration reference sera. Tetanus and diphtheria toxin
      concentrations are expressed in IU/ml with a WHO international reference sera as
      a standard. RESULTS: For diphtheria 100% of the children had antibody titers
      above the minimum protective level of 0.01 IU/ml and 86 to 100% (depending on
      prior vaccine product) had titers >0.1 IU/ml. However, only 0 to 40% of the
      children had antibody titers > or =1.0 IU/ml, a titer associated with more
      certain durable protection. For tetanus none of the children had an antibody
      titer below 0.01 IU/ml, and 93 to 100% had titers > or =0.1 IU/ml, a titer
      associated with more certain, durable protection. For pertussis the geometric
      mean concentrations of antibody before booster were uniformly very low, and the
      percentage of children exceeding the minimum detectable titer of antibody by 4
      fold was also low. CONCLUSION: Before a 4- to 6-year-old booster, a large
      proportion of children have titers of antibody to diphtheria below the certain,
      durable protective level. Because serologic correlates and minimum protective
      titers of antibody to pertussis antigens have not been established, the relevance
      of the low titers determined in the current study is unknown but a potential
      concern.

PMID- 11332670
TI  - Laboratory diagnosis of ehrlichiosis and babesiosis.
AB  - Over the past 15-20 years, four notable tick-borne infections have emerged in the
      US, Lyme disease, human monocytic ehrlichiosis (HME), human granulocytic
      ehrlichiosis (HGE) and babesiosis (Table). In contrast to the laboratory
      diagnostic procedures established for Lyme disease, RMSF and tularemia, the
      laboratory diagnostic procedures for the diagnosis of HME, HGE and babesiosis are
      not yet standardized and continue to be revised.

PMID- 11332671
TI  - Pulmonary lymphadenopathy.

PMID- 11332672
TI  - Congenital tuberculosis presenting as sepsis syndrome: case report and review of
      the literature.
AB  - We report an infant with congenital tuberculosis who presented with fulminant
      septic shock, disseminated intravascular coagulation and respiratory failure.
      Aggressive resuscitation and supportive care and prompt initiation of
      antituberculosis medications led to resolution of the shock state. We reviewed
      six other cases with a similar presentation. Congenital tuberculosis should be in
      the differential of the infant presenting acutely with sepsis syndrome.

PMID- 11332673
TI  - Unsuspected sporotrichosis in childhood.
AB  - We report 10 prepubertal girls with sporotrichosis who were misdiagnosed because
      they had solitary ulcerative skin nodules, rather than a "sporotrichoid" pattern
      of multiple linear nodules. All had positive cultures for Sporothrix schenckii.
      We urge clinicians to consider sporotrichosis in the differential diagnosis of a
      solitary skin nodule.

PMID- 11332674
TI  - Group C streptococcal meningitis: case report and review of the literature.
AB  - Group C streptococci are a common cause of epidemic bacterial infection in
      animals. These organisms are a rare but frequently fatal cause of meningitis in
      humans. We report the case of a 13-year-old girl with meningitis caused by a
      group C Streptococcus (Streptococcus zooepidemicus) successfully treated with
      vancomycin and third generation cephalosporins. We also review cases of group C
      streptococcal meningitis reported previously.

PMID- 11332675
TI  - Transfer of human herpesvirus 6 and 7 antibodies from mothers to their offspring.
AB  - Placental transfer of maternal human herpesvirus (HHV) 6 and HHV 7 antibodies to
      infants was examined simultaneously in 69 paired plasma samples by an indirect
      immunofluorescence assay. All the mothers had antibodies to both viruses. The
      mean HHV 6 and HHV 7 antibody titers of infants were significantly higher than
      those of the mothers. The mean ratio of cord blood antibody titer to the maternal
      titer for both viruses was 1.89, suggesting active transport by placenta.

PMID- 11332676
TI  - Systemic lupus erythematosus in a pediatric patient with congenital acquired
      immunodeficiency syndrome.
AB  - The coexistence of congenital HIV infection with primary rheumatologic disease is
      rare. We have described a child with congenital AIDS and concurrent systemic
      lupus erythematosus who presented with small vessel vasculitis with no renal
      involvement. Oral corticosteroid therapy resulted in significant improvement in
      her clinical state. The child also responded strongly to potent antiretroviral
      therapy both virologically and immunologically.

PMID- 11332677
TI  - Nonopsonic phagocytosis of Pseudomonas aeruginoas: insights from an infant with
      leukocyte adhesion deficiency.
AB  - Children with leukocyte adhesion deficiency type I are at risk for overwhelming
      infection because their neutrophils lack surface beta 2 integrins (CD18/CD11)
      that normally interact with endothelial cell adhesion molecules and mediate
      migration to sites of bacterial invasion. In vitro studies of phagocytic cells
      from an infant with leukocyte adhesion deficiency type I demonstrated that
      complement receptor 3 (CD18/CD11b) mediates nonopsonic phagocytosis of some
      Pseudomonas aeruginosa strains and might play a control role in the control of
      Pseudomonas infections at sites where there are low levels of opsonins.

PMID- 11332678
TI  - Kingella kingae endocarditis in a sixteen-month-old-child.
AB  - We report the case of a child with acute neurologic symptoms who was found to
      have bacterial endocarditis caused by Kingella kingae. The case alerts
      microbiologists and pediatricians to an organism that has rarely been reported to
      cause endocarditis in children.

PMID- 11332679
TI  - Successful treatment of visceral leishmaniasis with allopurinol plus ketoconazole
      in an infant who developed pancreatitis caused by meglumine antimoniate.
AB  - Pentavalent antimony is still the drug of choice in the treatment of visceral
      leishmaniasis. Pantavalent antimony can cause a wide range of adverse effects,
      the most serious of which are cardiotoxicity and hepatotoxicity. Acute
      pancreatitis is a rarely reported adverse effect. An infant who developed
      pancreatitis during meglumine antimoniate treatment for visceral leishmaniasis
      and who was successfully treated with a combination of allopurinol and
      ketoconazole is reported.

PMID- 11332680
TI  - Severe neonatal enteroviral hepatitis treated with pleconaril.
AB  - Neonatal enteroviral hepatitis carries high morbidity and mortality. We treated
      three full term neonates with severe enteroviral hepatitis with pleconaril on an
      open label compassionate use protocol. Each mother had history of a viral-like
      syndrome within 1 week before delivery. The neonates presented at 4 to 5 days of
      age with fulminant hepatic failure with severe coagulopathy, and each yielded an
      echovirus. All were treated with pleconaril (VP63843) at 5 mg/kg every 8 h by
      nasogastric tube. Two of the three neonates with life-threatening enteroviral
      hepatitis recovered fully. Further experience with pleconaril for neonatal
      enteroviral hepatitis is warranted.

PMID- 11332681
TI  - Hypothermia as a risk factor for pediatric cardiothoracic surgical site
      infection.

PMID- 11332682
TI  - Quantitative enzyme-linked immunosorbent assays for diagnosis of human
      immunodeficiency virus infection in infancy.
AB  - In countries where HIV infection is common and health care resources are limited,
      identification of HIV-infected infants is difficult because PCR testing is not
      affordable. Available enzyme-linked immunosorbent assay tests (AXSYM System;
      Abbott) set a cutoff point of 1; by changing this point to 10, HIV-infected
      infants can be identified at a young age.

PMID- 11332683
TI  - Cutaneous lesions of disseminated cryptococcosis as the presenting manifestation
      of human immunodeficiency virus infection in a twenty-two-month-old child.
AB  - We report the case of a 22-month-old African boy with cutaneous lesions as the
      predominant feature of disseminated cryptococcosis (positive blood and
      cerebrospinal fluid cultures) and as the presenting manifestation of severe
      vertically acquired HIV infection (CDC C3 category). To our knowledge these
      cutaneous lesions have never been reported as the initial manifestation of AIDS
      in children.

PMID- 11332684
TI  - Seven-year-old Indian girl with fever and cervical lymphadenitis. Kikuchi
      Fujimoto disease.

PMID- 11332685
TI  - Antibiotic therapy of colitis.

PMID- 11332686
TI  - Treatment of otorrhea.

PMID- 11332687
TI  - Disseminated rashes and varicella vaccine.

PMID- 11332688
TI  - Treatment of otitis media.

PMID- 11332689
TI  - The localization of thrombospondin-1 (TSP-1), cysteine-serine-valine-threonine
      cysteine-glycine (CSVTCG) TSP receptor, and matrix metalloproteinase-9 (MMP-9) in
      colorectal cancer.
AB  - Thrombospondin-1 (TSP-1) is a 450 kDa matrix bound glycoprotein involved in tumor
      invasion, metastasis, and angiogenesis. One of the receptors involved in TSP-1
      mediated tumor cell adhesion and metastasis is the cysteine-serine-valine
      threonine-cysteine-glycine (CSVTCG) receptor. One mechanism of TSP-1 in promoting
      tumor cell metastasis involves the up-regulation of matrix metalloproteinase-9
      (MMP-9) expression, specifically through the CSVTCG TSP-1 receptor. TSP-1 and its
      CSVTCG receptor has been implicated in tumor progression in a variety of cancers
      including breast adenocarcinomas, head and neck squamous cell carcinomas, and
      pancreatic carcinomas. In this study, we examined 99 cases of colorectal cancer
      by immunohistochemical analysis to investigate 1) the localization of TSP-1 and
      CSVTCG TSP-1 receptor, 2) the relationship with MMP-9, and 3) the correlation of
      expression with clinical staging. Strong expression of TSP-1 was observed in the
      submucosa or the serosa adjacent to the tumor. Positive staining for CSVTCG TSP-1
      receptor was observed in tumor cells and microvessels. MMP-9 was also expressed
      in tumor cells. In addition, staining intensity of CSVTCG TSP-1 receptor was
      higher in poorly differentiated adenocarcinoma than well or moderately
      differentiated adenocarcinoma. Tumors in which inflammatory cells stained
      strongly for CSVTCG TSP-1 receptor correlated with decreased incidence of distant
      metastasis and angiogenesis. These data were consistent with our previous studies
      for breast, pancreatic, and head and neck carcinoma. They suggest an important
      role for TSP-1 and CSVTCG TSP-1 receptor in tumor progression in colorectal
      cancer.

PMID- 11332690
TI  - Beta-catenin expression pattern in small cell lung cancer: correlation with
      clinical and evolutive features.
AB  - Beta-catenin expression in small cell lung carcinomas (SCLC) was investigated by
      immunohistochemical method using antibodies against beta-catenin. 50 pre
      treatment biopsies were examined and the relationship between beta-catenin
      expression and the patients' relevant clinical characteristics, response to
      chemotherapy, time to relapse or progression, and overall survival, were
      analyzed. Beta-catenin expression exhibited different intensity within each
      sample, predominantly localized in the cytoplasm, and no sample showed nuclear
      expression. There was cytoplasmic hyperexpression in 14 cases, hypoexpression in
      15 cases, and normal expression in 21 cases. We did not find any association
      between beta-catenin expression and clinical data. Our results show, however,
      correlation between beta-catenin cytoplasmic hyperexpression with a shorter time
      to progression (p=0.0437) as well as with a shorter overall survival (p=0.0253).
      Beta-catenin hyperexpression could have prognostic significance in SCLC.

PMID- 11332691
TI  - Expression of VEGF-C and activation of its receptors VEGFR-2 and VEGFR-3 in
      trophoblast.
AB  - Placental villous development requires the co-ordinated action of angiogenic
      factors on both endothelial and trophoblast cells. Like vascular endothelial
      growth factor (VEGF), VEGF-C increases vascular permeability, stimulates
      endothelial cell proliferation and migration. In the present study, we
      investigated the expression of VEGF-C and its receptors VEGFR-3 and VEGFR-2 in
      normal and intrauterine growth-restricted (IUGR) placenta. Immunolocalisation
      studies showed that like VEGF and VEGFR-1, VEGF-C, VEGFR-3 and VEGFR-2 co
      localised to the syncytiotrophoblast, to cells in the maternal decidua, as well
      as to the endothelium of the large placental blood vessels. Western blot analysis
      demonstrated a significant decrease in placental VEGF-C and VEGFR-3 protein
      expression in severe IUGR as compared to gestationally-matched third trimester
      pregnancies. Conditioned medium from VEGF-C producing pancreatic carcinoma (Suit
      2) and endometrial epithelial (Hec-1B) cell lines caused an increased association
      of the phosphorylated extracellular signal regulated kinase (ERK) in VEGFR-3
      immunoprecipitates from spontaneously transformed first trimester trophoblast
      cells. VEGF121 caused dose-dependant phosphorylation of VEGFR-2 in trophoblast
      cells as well as stimulating DNA synthesis. In addition, premixing VEGF165 with
      heparin sulphate proteoglycan potentiated trophoblast proliferation and the
      association of phospho-ERK with the VEGFR-2 receptor. VEGF165-mediated DNA
      synthesis was inhibited by anti-VEGFR-2 neutralising antibody. The results
      demonstrate functional VEGFR-2 and VEGFR-3 receptors on trophoblast and suggest
      that the decreased expression of VEGF-C and VEGFR-3 may contribute to the
      abnormal villous development observed in IUGR placenta.

PMID- 11332692
TI  - Immunohistochemical expression of the p53, mdm2, p21/Waf-1, Rb, p16, Ki67, cyclin
      D1, cyclin A and cyclin B1 proteins and apoptotic index in T-cell lymphomas.
AB  - Fifty-seven cases of T-cell lymphomas (TCL) including 5 lymphoblastic (T-LBL) and
      52 peripheral TCL (PTCL) were analyzed by immunohistochemistry for the expression
      of p53, mdm2, p21, Rb, cyclin D1, cyclin A, cyclin B1, and Ki67/MIB1 proteins and
      39/52 PTCL were also analyzed for the expression of p16 protein and for the
      presence of apoptotic cells by the TUNEL method. The aim was to search for
      abnormal immunoprofiles of p53 and Rb growth control pathways and to determine
      the proliferative activity and the apoptotic index of TCL. Abnormal
      overexpression of p53, p21 and mdm2, in comparison to normal lymph nodes, was
      found in 12/57, 10/57 and 2/57 cases of TCL, respectively. Abnormal loss of Rb
      and p16 expression was found in 1/57 and 2/39 cases, respectively, whereas
      abnormal overexpression of cyclin D1 was not detected in any of the 57 cases. Our
      data revealed entity-related p53/p21/mdm2 phenotypes. Indeed, most nodal and
      cutaneous CD30+ anaplastic large cell lymphomas (ALCL) showed concomitant
      overexpression of p53 and p21 proteins (7/8 cases), and mdm2 was overexpressed in
      2 p53-positive nodal ALCL. In contrast, overexpression of p53 was found in 3/17
      cases of nodal peripheral TCL unspecified (PTCL-UC) and 2/7 non-ALCL cutaneous
      pleomorphic TCL. Overexpression of p21 protein was detected in 2/3 p53-positive
      PTCL-UC and in 1/2 p53-positive non-ALCL cutaneous pleomorphic TCL. Finally, all
      the remaining 25 cases of TCL did not show p53 and p21 overexpression. Overall,
      the p53+/p21+ phenotype in 10/57 TCL suggests wild-type p53 capable of inducing
      p21 expression. The highest apoptotic index (AI) was found in ALCL and a positive
      correlation between apoptotic index and Ki67 index (p<0.001) was detected. Ki67,
      cyclin A and cyclin B1 expression was found in all 57 TCL and on the basis of the
      combined use of these 3 variables, 3 groups of proliferative activity could be
      determined: a) high in ALCL and T-LBL, b) low in mycosis fungoides (MF) and
      gammadelta hepatosplenic TCL, and c) intermediate in the remaining TCL entities.
      The proliferative activity in the 12 p53 overexpressing cases was higher in
      comparison to the 45 p53-negative cases. Ki67 expresion in more than 25% of
      tumour cells showed significant correlation with p53 overexpression (p<0.001). Rb
      expression tended to be parallel to Ki67, cyclin A and cyclin B1 expression in
      all but one case of nodal PTCL-UC which displayed loss of RB expression.
      Interestingly, this case was p53-negative, whereas the p53-positive cases were Rb
      positive. These findings suggest that different pathogenetic routes may function
      in some TCL, involving either the p53 or, less frequently, the Rb pathways.

PMID- 11332693
TI  - Papillary adenoma of the kidney with mucinous secretion.
AB  - Although infrequently, mucin secretion has previously been reported in papillary
      renal cell carcinoma. We here investigate the presence of mucin in a series of 93
      renal papillary adenomas in 58 patients. Acid mucin was present in four cases
      (4.3% of the tumors; 6.9% of the patients), in which basophilic mucin secretion
      was evident with hematoxylin-eosin. To the best of our knowledge mucin secretion
      has not been reported in renal papillary adenoma. We describe two different types
      of mucin secretion: intracytoplasmic and luminal. The secretion was intracellular
      in numerous scattered tumor cells in two cases, focal luminal in one case, and
      mixed intracellular and luminal in another case. Mucin production, despite its
      low frequency, can be considered as an additional feature of renal papillary
      adenoma. Mucin production suggests that renal papillary adenoma and papillary
      renal cell carcinoma are actually not two independent biological processes, but a
      continuum of one biological process.

PMID- 11332694
TI  - Effect of diabetic state on co-localization of substance P and serotonin in the
      gut in animal models.
AB  - Changes in the numbers of serotonin- and substance P-immunoreactive (IR) cells
      occur in several animal models of diabetes. It is not known, however, whether
      these changes are a result of actual cell loss or are caused by modified gene
      expression in cells showing co-localization of serotonin and substance P. The
      pattern of mono- and co-expression of serotonin, as well as of substance P, was
      therefore investigated in gastrointestinal endocrine cells from animal models of
      human type 1 and type 2 diabetes, namely non-obese diabetic (NOD) and obese
      diabetic (ob/ob) mice. Immunocytochemical staining by the avidin-biotin complex
      method was performed for computerized image analysis of each cell type, and by
      immunofluorescence double staining to study co-localization. Tissues from antrum,
      proximal duodenum and distal colon were investigated. Co-localization of
      serotonin- and substance P-IR was found in all investigated parts of the gut. In
      antrum, substance P immunoreactivity was found exclusively in serotonin-IR cells.
      In both NOD and ob/ob mice there was a reduced number of substance P-IR cells,
      but an unchanged serotonin-IR cell count, which thus tallies with a shut-off of
      substance P expression in antral enterochromaffin cells. In duodenum, both
      diabetes models showed a decreased number of serotonin-IR cells. Furthermore
      there was a decreased number of substance P-IR cells in the type 2 model. The
      proportion of serotonin-IR cells showing substance P-immuno-reactivity was
      decreased in both diabetic models, thus indicating a shut-off of substance P-gene
      expression. However, this does not fully explain the changes in duodenum, but the
      diabetic state probably affects the number of mono-expressed cells as well. In
      colon, no change was found in diabetic mice regarding co-localization of
      substance P and serotonin. However, pre-diabetic NOD mice showed a decreased
      proportion of substance P in serotonin-IR cells, which might be explained by the
      increased number of serotonin-IR cells, combined with an unchanged number of
      substance P-IR cells. In conclusion, diabetic animal models of both type 1 and
      type 2 appear to have a combination of decreased expression of substance P in
      serotonin-IR cells of both antrum and duodenum, as well as a change in the number
      of mono-expressed cells. The pattern in colon, on the other hand, seems to be
      unaffected.

PMID- 11332695
TI  - MIB1 proliferation index in breast infiltrating carcinoma: comparison with other
      proliferative markers and association with new biological prognostic factors.
AB  - AIMS: In breast invasive carcinoma our objectives were I) to compare cellular
      proliferation determined by MIB1 index with S-phase fraction (SPF) assessed by
      flow cytometry and with mitotic index, and II) to examine the association of MIB1
      index with classical and with new biological prognostic factors [bcl-2, p53, c
      erbB-2 and cathepsin D (CD)]. METHODS AND RESULTS: From 102 cases of breast
      invasive carcinoma, 5-microm thick serial sections were cut from formalin-fixed,
      paraffin-embedded tissue blocks, and processed for detection of CD, c-erbB-2,
      p53, bcl-2, Ki-67 antigen MIB-1 and estrogen receptors (ER) and progesterone
      receptors (PR). SPF was measured by flow cytometry in fresh-frozen tissue samples
      taken from the carcinoma in each patient. MIB1 index was correlated with SPF
      (rho=0.45, p<0.0001) and with mitotic index (rho=0.42, p<0.0001). The MIB-1 index
      was positively associated with the histological grade (p=0.001), tumor size
      (p=0.04) and the presence of metastases in axillary lymph nodes (p=0.01). MIB1
      was associated directly with p53 (p=0.045) and inversely with bcl-2 (p=0.0002).
      The MIB-1 index was not statistically associated with c-erbB-2. There was a weak
      association between MIBI index and stromal cell CD. The median MIB1 index was
      higher in tumors with moderate to strong CD staining of stromal cell, but the
      difference did not reach statistical significance (p=0.09). CONCLUSIONS: MIB1
      index correlates with well established methods for assessing tumor proliferation
      and with parameters of an aggressive phenotype of tumor. MIB1 index is an
      effective and readily accessible method for assessing tumor proliferation in
      breast carcinoma.

PMID- 11332696
TI  - Decrease in calcitonin and parathyroid hormone mRNA levels and hormone secretion
      under long-term hypervitaminosis D3 in rats.
AB  - In calcium homeostasis, vitamin D3 is a potent serum calcium-raising agent which
      in vivo regulates both calcitonin (CT) and parathyroid hormone (PTH) gene
      expression. Serum calcium is the major secretagogue for CT, a hormone product
      whose biosynthesis is the main biological activity of thyroid C-cells. Taking
      advantage of this regulatory mechanism, long-term vitamin D3-induced
      hypercalcemia has been extensively used as a model to produce hyperactivation,
      hyperplasia and even proliferative lesions of C-cells, supposedly to reduce the
      sustained high calcium serum concentrations. We have recently demonstrated that
      CT serum levels did not rise after long-term hypervitaminosis D3. Moreover, C
      cells did not have a proliferative response, rather a decrease in CT-producing C
      cell number was observed. In order to confirm the inhibitory effect of vitamin D3
      on C-cells, Wistar rats were administered vitamin D3 chronically (25,000 IU/d)
      with or without calcium chloride (CaCl2). Under these long-term vitamin D3
      hypercalcemic conditions, calcium, active metabolites of vitamin D3, CT and PTH
      serum concentrations were determined by RIA; CT and PTH mRNA levels were analysed
      by Northern blot and in situ hybridization; and, finally, the ultrastructure of
      calciotrophic hormone-producing cells was analysed by electron microscopy. Our
      results show, that, in rats, long term administration of vitamin D3 results in a
      decrease in hormone biosynthetic activities of both PTH and CT-producing cells,
      albeit at different magnitudes. Based upon these results, we conclude that
      hypervitaminosis D3-based methods do not stimulate C-cell activity and can not be
      used to induce proliferative lesions of calcitonin-producing cells.

PMID- 11332697
TI  - Prodigiosin induces cell death and morphological changes indicative of apoptosis
      in gastric cancer cell line HGT-1.
AB  - Gastric cancer is one of the most frequent malignancies and its treatment is far
      from satisfactory. The challenge to oncologists is the characterization of novel
      chemical entities with greater effectiveness. Prodigiosin is a red pigment
      produced by various bacteria including Serratia marcescens. Here we characterize
      the apoptotic action of prodigiosin in human gastric carcinoma cell line (HGT-1).
      Cells were assayed by the MTT assay, fragmentation pattern of DNA, Hoechst 33342
      staining and study of actin microfilament architecture. Treatment of these cells
      with prodigiosin showed a constant decrease in viability by apoptosis.
      Morphological analysis of prodigiosin-treated cells demonstrated that prodigiosin
      induces cell shrinkage, chromatin condensation, reorganization of actin
      microfilament architecture, and detachment of cells from the cell culture
      substrate. Altogether these results suggest that prodigiosin induces apoptosis in
      HGT-1 human gastric cancer cells and raises the possibility of its use as a new
      chemotherapeutic drug.

PMID- 11332698
TI  - The hepatocytes of the brown trout (Salmo trutta f. fario): a quantitative study
      using design-based stereology.
AB  - A stereological study was performed on brown trout hepatocytes aiming to disclose
      whether there are basic gender differences when minimal levels of sex hormones
      exist, and also to establish a platform for both interspecific comparisons and
      physiological correlations. We used the so-called "design-based stereology" (with
      no shape, size or orientation assumptions) and also some new related statistics.
      Two-year-old brown trout were collected in April, and the livers were fixed by
      perfusion. From liver slicing to microscopical field selection, systematic
      sampling was used. Stereology was applied at light and electron microscopy.
      Target parameters were the relative and total hepatocyte number, the mean
      individual hepatocyte volume and surface, and also both relative and total
      volumes, and surfaces, either of organelles or of cell compartments. Observed
      variability was usually high, but the precision of estimates was proved to be
      globally adequate facing the true biological variation amongst specimens. Females
      had more hepatocytes per liver (1.79x10(9) vs. 1.12x10(9)). Considering the
      individual hepatocytes, whereas no gender differences were detected in the cell
      volume, males had higher values of nuclear volume (199 vs. 151 microm3) and
      surface (170 vs. 131 microm2), endoplasmic reticulum volume (1,300 vs. 824
      microm3), and microvilli volume (82 vs. 54 microm3) and surface (1,445 vs. 975
      microm2). However, when dealing with quantities per liver, gender differences
      were found only in the volumes of dense bodies (56 vs. 97 mm3) and of residual
      cytoplasm (169 vs. 341 mm3)--both volumes were higher in females. Functional
      implications of data are discussed, namely that females seem to have basic
      structural traits for coping with the later demands of breeding. Data also
      support that structural remodelling of hepatocytes occurs after breeding, urging
      to pursue seasonal studies (namely on lysosomes). We advanced the hypothesis that
      genders differ in microvilli surface just to maintain an optimal physiological
      surface-to-volume ratio. Interspecific similarities and differences were
      disclosed. For example, the number of hepatocytes/cm3 of parenchyma of brown
      trout was much lower than those reported in rainbow trout, but in both trouts
      females seem to have an higher cell number. In addition, when comparing the size
      of hepatocytes of brown trout with that from other fish and mammals it was
      suggested that major interspecific differences exist.

PMID- 11332699
TI  - The histochemical profiles of fibre types in porcine skeletal muscle.
AB  - Using a variety of histochemical methods -mATPase staining after alkaline and
      acid preincubations, NADH-TR and alpha-MGPDH- we have investigated the fibre
      types in porcine skeletal muscle. The results reveal that four major fibre types 
      I, IIA, IIB and II*- can be separated histochemically in Longissimus lumborum
      muscle of Landrace pigs. The histochemical properties of the muscle fibre type
      II* are very similar to that of type IIX described in other mammals. The
      existence of IIX fibres in pig muscle has been recently demonstrated by molecular
      biology techniques and our results validate the use of histochemistry (mATPase)
      as an easy methodology to differentiate the three fast myosins (type II fibres)
      in pig muscle.

PMID- 11332700
TI  - Immunocytohistochemical characterization of pituitary cells of the bluefin tuna,
      Thunnus thynnus L.
AB  - In this paper we report the first complete mapping of the pituitary in a tuna
      species. The various different adenohypophysis cell types of the bluefin tuna,
      Thunnus thynnus L. have been identified and located using different antisera
      against mammalian and piscine hormones and various histochemical techniques: PAS,
      Alcian Blue pH 2.5 and lectins -ConA and WGA(Neutral and Acidic Glycoproteins);
      Bromophenol Blue (Proteins) and Tioglycollate-Ferric-Ferricianide-FeIII (-S-S-
      groups). Prolactin (PRL) and adrenocorticotrophic (ACTH) cells were located in
      the rostral pars distalis (RPD) of the pituitary, while the proximal pars
      distalis (PPD) displayed gonadotrophic (GTH), thyrotrophic (TSH), somatotrophic
      (GH) and also a few PRL cells. Moreover, somatolactin (SL) and melanotrophic
      (MSH) cells were identified inside the pars intermedia (PI). Interestingly, some
      SL-immunoreactive fibers were also detected in the neurohypophysis. Some GTH
      cells were also located on the exterior surface of the PI. Glycoproteins
      containing mannose (Man) and/or glucose (Glc); N-acetyl-glucosamine (GlcNAc)
      and/or sialic acid sugar residues, as well as -S-S- groups, were observed in GTH,
      TSH and SL cells. The Bromophenol Blue technique stained amphiphilic SL,
      acidophilic GH cells and weakly ACTH cells. GH and ACTH cells were unreactive to
      PAS, Alcian Blue, Tioglycollate-Ferric-Ferricianide-FeIII and lectin (Con A and
      WGA) techniques. Finally, PAS reaction was positive in amphiphilic SL cells,
      which were PbH unreactive, while MSH and ACTH cells were stained with PbH
      technique.

PMID- 11332701
TI  - Intravesicular Fas localization in epithelial cells of castrated rat prostate
      glands.
AB  - Androgenic steroids regulate the development and size of mammalian prostate
      epithelial cells. To evaluate the relationship between Fas-Fas ligand system and
      apoptosis in prostate epithelial cells of the castrated rats, we have examined
      immunocytochemical localization of Fas antigen in the castrated rat prostate
      glands at a series of different times. We used a rabbit polyclonal anti-Fas
      antibody with a streptavidin-biotin method and confocal laser scanning method or
      an immunogold method. Fas immunolocalization was examined in ventral lobes of
      prostate glands taken from intact or castrated adult male Wistar rats on day 1,
      2, 3, 4 and 5 by light or electron microscopy. At a light microscopic level, the
      castrated prostate epithelial cells showed mostly Fas immunolocalization in their
      apical parts of cytoplasm on day 2 after the castration. In addition, their
      extent of the Fas expression was expanded throughout the cytoplasm in proportion
      to the androgen ablation periods, and later the Fas expression was detected at
      luminar or basolateral sides of the epithelial cells. Both immunogold labeling
      with ultrathin sections and immunoperoxidase technique with cryostat sections
      demonstrated that Fas was localized mainly in secretory granules of the castrated
      prostate epithelial cells and some parts of their cell membranes at later stages.
      Our immunocytochemical findings showed that Fas expression was time-dependently
      induced in most of the prostatic epithelial cells after castration of rats. The
      rate of Fas-expressing epithelial cells was too high and inconsistent with the
      previously reported rate of TUNEL-positive ones. The membrane-associated Fas may
      have little effect on the apoptosis in the present case, bacause a lot of soluble
      Fas was secreted from the prostatic epithelial cells. A further study is needed
      to clarify some significance of the secretory Fas in the prostatic epithelium
      after the rat castration.

PMID- 11332702
TI  - Appearance of vascular endothelial growth factor (VEGF) in femoral head in the
      growing rat.
AB  - In this study, we examined the appearance of vascular endothelial growth factor
      (VEGF) in the femoral head of the growing rat using an immunocytochemical
      technique. Our results showed VEGF-immunopositive cells existed in the inner
      region and peripheral region of the femoral head at each developmental stage. In
      the 19-day-old fetus, immunopositive mesenchymal cells were demonstrated in the
      peripheral region of the femoral head. At 1 to 10 days after birth, VEGF
      immunoreactivities were observed in the osteoblasts, osteoclasts, periosteum,
      perichondrium and cartilage matrix of the femur. At 15 days after birth, VEGF
      immunoreactive chondrocytes appeared in the apex area of the femoral head. In
      this stage, the femoral head is still constituted by chondrocytes and no apparent
      vascular formation has been observed. Thereafter, the immunopositive chondrocytes
      in the femoral head increased in number. The penetration of capillaries was
      recognized within the ligament of the femoral head at 60 days after birth. The
      results indicate that some chondrocytes in the femoral head produce VEGF before
      the beginning of ossification, and that VEGF may play an important role in the
      penetration of blood vessels into the femoral head from the ligament of the
      femoral head.

PMID- 11332703
TI  - Blocking of histamine H2 receptors enhances parietal cell degeneration in the
      mouse stomach.
AB  - The effects of the histamine H2 receptor antagonist, ranitidine, on parietal cell
      lineage was studied in the mouse stomach by using light and electron microscopy
      techniques. Mice were continuously infused for 15, 30, and 42 hr with ranitidine.
      Semithin sections examined under the light microscope revealed spherical light
      areas in the cytoplasm of parietal cells which in thin sections under the
      electron microscope appeared to be vacuoles. Cells were categorized as normal,
      altered and damaged. While altered cells were characterized by dilated canaliculi
      and vacuoles, the damaged cells showed signs of necrosis or apoptosis. In control
      mice, altered and damaged parietal cells were consistently few and only found in
      the pit or base regions of the epithelial units. After 15-hr-treatment with
      ranitidine, 40% of the parietal cells were altered. After 30 hr infusion, altered
      parietal cells became 53% of the examined population, and after 42 hr, 72% of the
      parietal cells were affected (42% altered and 30%, damaged). The gradual increase
      in parietal cell vacuolation was associated with an increase in the census of pre
      parietal cells. Some mice were allowed to recover from treatment for 4 days. The
      appearance of normal parietal cells and disappearance of damaged cells was
      observed and the gastric glands became morphologically normal. In conclusion,
      inhibiting acid secretion by blocking the histamine H2 receptors, enhanced not
      only the degenerative elimination of parietal cells but also the production of
      pre-parietal cells and thus, the recovery of the population was prompt.

PMID- 11332704
TI  - Prolonged immobilization-induced stress delays alveolar bone healing. A
      histometric study in rats.
AB  - The purpose of the present study was to investigate the effect of prolonged
      immobilization-induced stress on reparative bone formation, using the rat
      alveolar healing as an experimental protocol. Stress was attained by
      immobilization for 2 hours a day, beginning three days before extraction of the
      upper right incisors and continuing until sacrifice. The stress condition was
      assayed on the basis of plasma corticosterone concentration (measured by double
      antibody radioimmunoassay), which increased by 2.5 to 4 times in rats submitted
      to immobilization. The volume density of neoformed bone filling the alveolar
      socket was quantified by a histometric differential point-counting method 7 to 21
      days following tooth extraction. Stress caused a significant delay in reparative
      bone increment, somewhat related to impairment of coagulum remission and/or
      organization.

PMID- 11332705
TI  - Acetylcholinesterase-positive and paraformaldehyde-induced-fluorescence-positive
      innervation in the upper eyelid of the sheep (Ovis aries).
AB  - This is the first study which describes the innervation of some eyelid
      structures, such as the glands of Moll and the glands of Zeiss. It is also the
      first to investigate the innervation pattern of the eyelid as a whole. We have
      studied the acetylcholinesterase-positive and paraformaldehyde-induced
      fluorescence-positive (FIF+) innervation pattern of the different structures that
      constitute the upper eyelid of the sheep. There is widespread
      acetylcholinesterase-positive innervation in the epithelium, but not such an
      abundant FIF+ innervation. Both types of innervation are represented in the
      connective tissue by trunks or fibers that are distributed towards the different
      structures immersed within them. In the glands of Zeiss, cholinesterase-positive
      innervation is much more widespread than FIF innervation. On the contrary, the
      glands of Moll present denser FIF+ innervation than acetylcholinesterase-positive
      innervation. The Meibomian glands and the lachrymal glands show a rich
      acetylcholinesterase-positive and FIF+ innervation. Eyelid muscle innervation is
      mainly acetylcholinesterase-positive. In the conjunctive membrane there is no
      acetylcholinesterase-positive innervation, and only scarce FIF+ fibers can be
      demonstrated.

PMID- 11332706
TI  - Early acquisition of bowel segment-specific Bcl-2 homolog expression profiles
      during development of the human ileum and colon.
AB  - The adult small and large intestines display distinct expression profiles of Bcl
      2 homologs, known regulators of apoptosis. This is thought to indicate that
      control mechanisms of intestinal apoptosis are gut segment-specific. Little is
      known on the expression of Bcl-2 homologs during gut development. In man,
      intestinal features and functions are acquired largely by mid-gestation (18-20
      wks); the question whether segment-specific controls of intestinal apoptosis are
      also acquired early during development remains open. In the present study, we
      approached this by investigating the expression of six Bcl-2 homologs (Bcl-2, Bcl
      XL, Mcl-1, Bax, Bak, Bad), and one nonhomologous associated molecule (Bag-1),
      during development of the human ileum and colon (12-20 wks of gestation).
      Beginning at 18 wks, we found that the epithelial localization of Bcl-2 homologs
      displayed differential patterns (or gradients) in both the ileum and colon;
      however, the patterns of some of the homologs differed between the two segments.
      For instance, Bag-1 and Bcl-2 exhibited crypt-villus decreasing gradients of
      expression in the ileum but not in the colon, whereas Mcl-1 displayed differing
      compartimentalizations between the two segments. Further analyses indicated that
      the steady-state expression levels of Bcl-2 homologs underwent modulations
      between 12 and 20 wks; however, the observed developmental profiles contrasted
      significantly between the two segments. For example, Bcl-2, Bag-1 and Bak levels
      increased in the colon, but the levels of these same homologs decreased in the
      ileum. Furthermore, by 18-20 wks, we found that the expression levels of each Bcl
      2 homolog analyzed differed greatly between the ileum and colon. Altogether,
      these data indicate that the expression of Bcl-2 homologs is modulated
      differentially during human gut development in order to establish, by mid
      gestation, distinct expression profiles for the small and large intestines. This
      in turn suggests that gut segment-specific control mechanisms of human intestinal
      apoptosis are acquired early during fetal life.

PMID- 11332707
TI  - Histological and histochemical observations in the stomach of the Senegal sole,
      Solea senegalensis.
AB  - An histological and histochemical study was conducted on the stomach of adult
      Senegal sole, Solea senegalensis specimens. The stomach was made up of four
      distinct layers: mucosa, lamina propria-submucosa-, muscularis and serosa.
      Surface epithelial, glandular and rodlet cells were present in the mucosa. Cells
      of the columnar epithelium contained a basal nucleus. Numerous mitochondria,
      granular endoplasmic reticulum and Golgi apparatus consisting of several parallel
      cisternae and vesicles were observed in the cytoplasm of these cells. The
      lysosomes were small, round and dense. The gastric glands were numerous in the
      pyloric and fundic regions but absent in the cardiac stomach. These glands were
      formed by two cell-types: light and dark cells. The light cells were
      characterised by numerous mitochondria, while dark cells had slightly fewer
      mitochondria and a tubulo-vesicular system. Rodlet cells similar to those
      observed in other teleostean fish were present among the epithelial cells.
      Although the epithelial cells of the mucosa contained a weak presence of neutral
      and acid mucopolysaccharides/mucosubstances, these substances were abundant in
      the lamina propria-submucosa. Proteins rich in arginine, lysine, cysteine and
      cystine were rarely present in the mucosa and lamina propria-submucosa of
      stomach, while proteins rich in tyrosine were abundant in these layers. Acid
      phosphatase, and ATP-ase (pH 7.2 and 9.4) activities were detected in the mucosa
      and lamina propria-submucosa. Alkaline phosphatase activity was not detected.

PMID- 11332708
TI  - Reactive oxygen species (ROS)-generating oxidases in the normal rabbit cornea and
      their involvement in the corneal damage evoked by UVB rays.
AB  - The corneas of albino rabbits were irradiated (5 min exposure once a day) with
      UVB rays (312 nm) for 4 days (shorter procedure) or 8 days (longer procedure).
      The eyes were examined microbiologically and only the corneas of sterile eyes or
      eyes with non-pathogenic microbes were employed. Histochemically, the activities
      of reactive oxygen species (ROS)-generating oxidases (xanthine oxidase, D-amino
      acid oxidase and alpha-hydroxy acid oxidase) were examined in cryostat sections
      of the whole corneas. Biochemically, the activity of xanthine
      oxidoreductase/xanthine oxidase was investigated in the scraped corneal
      epithelium. UVB rays significantly changed enzyme activities in the corneas. In
      comparison to the normal cornea, where of ROS-generating oxidases only xanthine
      oxidase showed significant activity in the corneal epithelium and endothelium, D
      amino acid oxidase was very low and alpha-hydroxy acid oxidase could not be
      detected at all, in the cornea repeatedly irradiated with UVB rays, increased
      activities of xanthine oxidase and D-amino acid oxidase were observed in all
      corneal layers. Only after the longer procedure the xanthine oxidase and D-amino
      acid oxidase activities were decreased in the thinned epithelium in parallel with
      its morphological disturbances. Further results show that the xanthine
      oxidase/xanthine oxidoreductase ratio increased in the epithelium together with
      the repeated irradiation with UVB rays. This might suggest that xanthine
      dehydrogenase is converted to xanthine oxidase. However, in comparison to the
      normal corneal epithelium, the total amount of xanthine oxidoredutase was
      decreased in the irradiated epithelium. It is presumed that xanthine
      oxidoreductase might be released extracellularly (into tears) or the enzyme
      molecules were denatured due to UVB rays (particulary after the longer
      procedure). Comparative histochemical and biochemical findings suggest that
      reactive oxygen species-generating oxidases (xanthine oxidase, D-amino acid
      oxidase) contribute to the corneal damage evoked by UVB rays.

PMID- 11332709
TI  - Endothelin-1[1-31] acts as a selective ETA-receptor agonist in the rat adrenal
      cortex.
AB  - Endothelin-1 (ET-1) is a 21-amino acid residue (ET-1[1-21]) hypertensive peptide,
      which together with its receptor subtypes A and B (ETA and ETB) is expressed in
      the rat adrenal cortex, where it stimulates steroid-hormone (aldosterone and
      corticosterone) secretion through the ETB receptor and the growth (proliferative
      activity) of the zona glomerulosa (ZG) through the ETA receptor. ET-1[1-21] is
      generated from bigET-1 by the endothelin-converting enzyme (ECE-1). However,
      recent evidence indicates the existence of an alternative chymase-mediated
      biosynthetic pathway leading to the production of an ET-1[1-31] peptide, which
      was found to reproduce the ETA receptor-mediated vascular effects of ET-1[1-21].
      We found that ET-1[1-21], but not ET-1[1-31], concentration-dependently raised
      steroid secretion from dispersed rat adrenocortical cells, its effect being
      blocked by the ETB-receptor selective antagonist BQ-788. Both ET-1s concentration
      dependently increased the number of "S-phase" cells (as detected by the 5-bromo
      2'-deoxyuridine immunocytochemical method) in capsule-ZG strips within a 240 min
      incubation. The ZG proliferogenic action of both ET-1s was blocked by the ETA
      receptor antagonist BQ-123, and ET-1[1-31] was found to be significantly more
      potent than ET-1[1-21]. Autoradiography showed that in the rat adrenal ET-1[1-21]
      displaced the binding of selective ligands to both ETA ([125I]PD-151242) and ETB
      receptors ([125I]BQ-3020), while ET-1[1-31] eliminates only the binding to ETA
      receptors. Collectively, our findings provide strong evidence that ET-1[1-31]
      acts in the rat adrenal glands as a selective ETA-receptor agonist, mainly
      involved in the stimulation of ZG proliferative activity.

PMID- 11332710
TI  - Post translational activation of latent transforming growth factor beta (L-TGF
      beta): clinical implications.
AB  - Transforming growth factor-betas (TGF-betas) are multifunctional cytokines that
      exist in 3 isoforms in mammals. The TGF-betas are ubiquitously expressed and all
      isoforms are secreted as biologically inactive precursors called latent TGF-beta
      (L-TGF-beta). L-TGF-betas are generally not effective molecules because they are
      unable to interact with their receptors. However, the removal of or
      conformational change of the precursor protein called the latency associated
      peptide (LAP) results in the generation of biologically active TGF-beta. In vitro
      active TGF-beta has many biological effects but from a clinical point of view one
      of the most recognized associations of aberrant TGF-beta production is with
      diseases characterized by enhanced connective tissue synthesis. Recently a number
      of observations in the context of fibrotic disorders suggest mechanisms of
      activation of L-TGF-beta1 in vivo. The recognition of mechanisms that activate L
      TGF-beta1 in vivo offers the possibility of interfering with the activation of L
      TGF-beta1 for therapeutic purposes.

PMID- 11332711
TI  - Molecular and cellular aspects and regulation of intestinal lactase-phlorizin
      hydrolase.
AB  - Carbohydrates are hydrolyzed in the intestinal lumen by specific enzymes to
      monosaccharides before transport across the brush border membrane of epithelial
      cells into the cell interior. The enzymes implicated in the digestion of
      carbohydrates in the intestinal lumen are membrane-bound glycoproteins that are
      expressed at the apical domain of the enterocytes. Absent or reduced activity of
      one of these enzymes is the cause of disaccharide intolerance and malabsorption,
      the symptoms of which are abdominal pain, cramps or distention, flatulence,
      nausea and osmotic diarrhea. Lactose intolerance is the most common intestinal
      disorder that is associated with an absence or drastically reduced levels of an
      intestinal enzyme, in this case lactase-phlorizin hydrolase (LPH). The pattern of
      reduction of activity has been termed late onset of lactase deficiency or adult
      type hypolactasia. It was thought that the regulation of LPH was post
      translational and was associated with altered structural features of the enzyme.
      Recent studies, however, suggest that the major mechanism of regulation of LPH is
      transcriptional. Other forms of lactose intolerance include the rare congenital
      lactase deficiency and secondary forms, such as those caused by mucosal injury,
      due to infectious gastroenteritis, celiac disease, parasitic infection, drug
      induced enteritis and Crohn's disease. This review will shed light on important
      strucural and biosynthetic aspects of LPH, the role played by particular regions
      of the LPH protein in its transport, polarized sorting, and function, as well as
      on the gene expession and regulation of the activity of the enzyme.

PMID- 11332712
TI  - The role of gicerin, a novel cell adhesion molecule, in development, regeneration
      and neoplasia.
AB  - Neurite outgrowth factor (NOF) is an extracellular matrix (ECM) protein in the
      laminin family and its ligand, gicerin, is a novel cell adhesion molecule in the
      immunoglobulin superfamily. Gicerin has a homophilic adhesive activity as well as
      a heterotypic manner to NOF. In the nervous systems, gicerin is expressed during
      developmental stage when neurons migrate or extend neurites to form a neural
      network. Gicerin promotes neurite extension and migration of embryonic neurons in
      vitro by its homophilic and heterophilic adhesion activities. Introduction of
      antigicerin antibody into early developing eyes perturbs the layer formation of
      neural retina. These data suggest that gicerin participates in the formation of
      neural tissues. Gicerin is also expressed in other non-neural tissues; in
      epithelia of trachea, kidney and oviduct, gicerin expression is restricted in the
      developmental period. In contrast, muscular tissues and endothelial cells express
      gicerin continuously even after maturation. Interestingly, gicerin re-appears
      strongly in the regenerating epithelia of trachea, kidney and oviduct, and also
      anti-gicerin antibody disrupts the healing process of trachea. Furthermore,
      gicerin and NOF are overexpressed in the chicken nephroblastomas (Wilm's tumor)
      and oviductal adenocarcinomas. In vitro analyses show that gicerin adhesive
      activities can promote binding among tumor cells and adhesion of tumor cells to
      NOF. A polyclonal antibody against gicerin also perturbs the re-attachment of
      cancer cells onto metastasizing sites. It is clear from these studies that
      gicerin is a potential effector for pathological tissue formation as well as for
      normal development.

PMID- 11332713
TI  - Protein kinase CK2 signal in neoplasia.
AB  - Protein kinase CK2 (previously known as casein kinase II) is a protein
      serine/threonine kinase that has been implicated in cell growth and
      proliferation. The focus of this review is on the apparent role of CK2 in cancer.
      Studies from several laboratories have shown a dysregulated expression of the
      kinase in tumors. Nuclear matrix and chromatin appear to be key sites for
      signaling of the CK2 activity in relation to cell growth. Several types of growth
      stimuli produce a common downstream response in CK2 by enhancing its nuclear
      shuttling. The neoplastic change is also associated with changes in intracellular
      localization of the kinase so that a higher nuclear localization is observed in
      tumor cells compared with normal cells. Experimental studies suggest that
      dysregulated expression of the alpha subunit of CK2 imparts an oncogenic
      potential in the cells such that in cooperation with certain oncogenes it
      produces a profound enhancement of the tumor phenotype. Recent studies have
      provided evidence that overexpression of CK2 in tumor cells is not simply a
      reflection of tumor cell proliferation alone but additionally may reflect the
      pathobiological characteristics of the tumor. Of considerable interest is the
      possibility that CK2 dysregulation in tumors may influence the apoptotic activity
      in those cells. Approaches to interfering with the CK2 signal may provide a
      useful means for inducing tumor cell death.

PMID- 11332714
TI  - Tumor cell "dead or alive": caspase and survivin regulate cell death, cell cycle
      and cell survival.
AB  - Cell death and cell cycle progression are two sides of the same coin, and these
      two different phenomenons are regulated moderately to maintain the cellular
      homeostasis. Tumor is one of the disease states produced as a result of the
      disintegrated regulation and is characterized as cells showing an irreversible
      progression of cell cycle and a resistance to cell death signaling. Several
      investigations have been performed for the understanding of cell death or cell
      cycle, and cell death research has remarkably progressed in these 10 years.
      Caspase is a nomenclature referring to ICE/CED-3 cysteine proteinase family and
      plays a central role during cell death. Recently, several investigations raised
      some possible hypotheses that caspase is also involved in cell cycle regulation.
      In this issue, therefore, we review the molecular basis of cell death and cell
      cycle regulated by caspase in tumor, especially hepatocellular carcinoma cells.

PMID- 11332715
TI  - Transcriptional regulation of the bcl-x gene encoding the anti-apoptotic Bcl-xL
      protein by Ets, Rel/NFkappaB, STAT and AP1 transcription factor families.
AB  - Transcription factors play an essential role in determining the fate of a cell by
      affecting the expression of target genes involved in proliferation, in
      differentiation and in programmed cell death. Under certain conditions, some of
      these factors are capable of deregulating expression of genes involved in the
      cell cycle and/or in programmed cell death resulting in uncontrolled
      proliferation of the cell. The focus of this review is on the transcriptional
      regulation of the bcl-x gene encoding the anti-apoptotic Bcl-xL protein. Since
      1999, several papers have implicated members of the Ets, Rel/NFkappaB, STAT and
      AP-1 families as transcription factors regulating bcl-x expression. A specific
      emphasis of these different transcription factor families on bcl-x regulation in
      hematopoietic cells is discussed.

PMID- 11332716
TI  - Cell adhesion molecules in human osteoblasts: structure and function.
AB  - Osteoblasts and bone lining cells form a near continuous layer covering the bone
      surface and interactions between these cells and the organic matrix of bone are
      important determinants of osteoblast proliferation and differentiation. In
      addition, cells of the osteoblast-lineage form functional communications with
      each other, with the extra-cellular matrix and with osteocytes through
      cytoplasmic processes extending through canaliculi in the bone. Together, these
      cells form a network of putative importance in the regulation of skeletal
      homeostasis. Cell-cell and cell-matrix interactions are mediated by members of
      several families of cell adhesion molecules, and knowledge of their interactions
      will be of fundamental importance in understanding the role of osteoblast in
      skeletal turnover. Here, the expression pattern of members of the major families
      of cell adhesion molecules by cells of the osteoblast lineage is reviewed.
      Special emphasis has been placed on human tissues. In addition, the possibility
      that cells at progressive stages of the osteoblast lineage have different
      profiles of cell adhesion molecule expression is explored, and the putative
      significance of cell-matrix interactions in human skeletal disease briefly
      discussed.

PMID- 11332717
TI  - Neuronal and mixed neuronal glial tumors associated to epilepsy. A heterogeneous
      and related group of tumours.
AB  - The group of brain tumors with mature components encompasses several pathological
      entities including: the ganglioneuroma; the gangliocytoma; the ganglioglioma; the
      desmoplastic ganglioglioma; the neurocitoma and a group of glioneuronal
      hamartomatous tumorous lesions, such as meningoangiomatosis. The dysembryoplastic
      neuroepithelial tumor is characterized by the presence of multiple cortical
      nodules made up of small, oligo-like cells and a myxoid pattern rich in
      mucopolysaccharides. Mature neuronal cells are frequently detected throughout the
      tumor. Most of them are associated with microhamartias in the adjacent brain and
      pharmacoresistant epilepsy. The excellent prognosis of the majority of these
      tumors and the potential for malignant transformation of the glial component in
      the ganglioglioma are the two most remarkable findings. Histological signs of
      anaplasia and greater mitotic and proliferative activities are associated with
      local recurrences. Atypical neurocytomas occur only exceptionally. Treatment
      choices are surgical resectioning and, in those cases presenting greater
      proliferative activity and cytological atypia, postoperative radiotherapy may be
      recommended. This paper reviews this heterogeneous group of neoplasms and
      hamartomatous lesions, pointing out presumable transitions among the different
      types of mixed neuronal and glial brain tumors. A single term of "mixed neuronal
      glial tumors" is defended, distinguishing different subgroups of tumors,
      depending on the predominant cellular component.

PMID- 11332718
TI  - Cross-talk between RON receptor tyrosine kinase and other transmembrane
      receptors.
AB  - RON is a transmembrane receptor tyrosine kinase that mediates biological
      activities of Macrophage Stimulating Protein (MSP). MSP is a multifunctional
      factor regulating cell adhesion, motility, growth and survival. MSP binding to
      RON causes receptor tyrosine phosphorylation leading to up-regulation of RON
      catalytic activity and subsequent activation of downstream signaling molecules.
      Recent studies show that RON is spatially and functionally associated with other
      transmembrane molecules including adhesion receptors integrins and cadherins, and
      cytokine and growth factor receptors IL-3 betac, EPOR and MET. For example, MSP
      induced cell shape change is mediated via RON-activated IL-3 betac receptor.
      Activation of integrins causes MSP-independent RON phosphorylation, and the
      integrin/RON collaboration regulates cell survival. Thus, RON can be activated
      without MSP by ligand stimulation of RON-associated receptors, and MSP-activated
      RON can cause ligand-independent activation of RON-associated receptors. As a
      result of the receptor cross-activation RON-specific pathways become a part of a
      signal transduction network of other receptors, and conversely signaling pathways
      activated by other receptors can be used by RON. This receptor collaboration
      extends the spectrum of cellular responses generated by MSP and by putative
      ligands of RON-associated receptors. However signaling pathways involved in the
      receptor cross-talk and underlying activation mechanisms remain to be
      investigated. The purpose of this review is to summarize data and to discuss a
      role of cross-talk between RON and other transmembrane receptors.

PMID- 11332719
TI  - The dynamics of cellular injury: transformation into neuronal and vascular
      protection.
AB  - Despite the immediate event, such as cerebral trauma, cardiac arrest, or stroke
      that may result in neuronal or vascular injury, specific cellular signal
      transduction pathways in the central nervous system ultimately influence the
      extent of cellular injury. Yet, it is a cascade of mechanisms, rather than a
      single cellular pathway, which determine cellular survival during toxic insults.
      Although neuronal injury associated with several disease entities, such as
      Alzheimer's disease, Parkinson's disease, and cerebrovascular disease was
      initially believed to be irreversible, it has become increasingly evident that
      either acute or chronic modulation of the cellular and molecular environment
      within the brain can prevent or even reverse cellular injury. In order to develop
      rational, efficacious, and safe therapy against neurodegenerative disorders, it
      becomes vital to elucidate the cellular and molecular mechanisms that control
      neuronal and vascular injury. These include the pathways of free radical injury,
      the independent mechanisms of programmed cell death, and the downstream signal
      transduction pathways of endonuclease activation, intracellular pH, cysteine
      proteases, the cell cycle, and tyrosine phosphatase activity. Employing the
      knowledge gained from investigations into these pathways will hopefully further
      efforts to successfully develop effective treatments against central nervous
      system disorders.

PMID- 11332720
TI  - A human in vitro granuloma model for the investigation of multinucleated giant
      cell and granuloma formation.
AB  - A method for the in vitro generation of granulomas and its use in the analysis of
      the human granulomatous response is summarized. As a target for the cellular
      response L3 larvae of Nippostrongylus brasiliensis are coincubated with human
      mononuclear blood cells, and within seven to fourteen days the development of
      blood monocytes to mature macrophages and to epithelioid cells and multinucleated
      giant cells (MGC) as typical constituents of granulomas clustered around the
      nematode is observed. The following review describes the uses and applications of
      this model for phenotyping, functional, formation and modulating studies of
      granulomas and MGCs, taking into account its unique features compared to other in
      vitro models. With respect to MGC formation, procedures are described and
      examples are given which allow the phenotyping of these cells using
      immunofluorescence and immunohistological techniques. In addition, the potential
      of this model for illuminating functional aspects of MGC is described applying an
      isolation protocol for MGC and a subsequent reverse-transcriptase polymerase
      chain reaction method for the analysis of single cells. Moreover, the
      significance and relevance of using this granuloma model is discussed in the
      follow up analysis of in vivo findings of interleukin-6 expression in MGC of
      granulomas of patients with sarcoidosis. These in vivo results implicated a role
      for interleukin-6 in granuloma and MGC development. The in vitro granuloma model
      was used to investigate potential modulatory effects of this cytokine by
      analysing the cell numbers and the number of MGC per in vitro granuloma, the size
      of the MGC formed, the fusion index and the morphology of the in vitro granuloma.
      The results demonstrated significant modulatory effects of interleukin-6 on the
      cell number per in vitro granuloma and on the morphology of the cells involved.
      Conceivably, elevated interleukin-6 levels may modulate granuloma formation with
      respect to the number of cells involved and in influencing distinct cell
      populations involved in granuloma formation.

PMID- 11332721
TI  - Towards a new generation of vaccines: the cytokine IL-12 as an adjuvant to
      enhance cellular immune responses to pathogens during prime-booster vaccination
      regimens.
AB  - A main goal of the industrialized world is the development of effective vaccines
      to control infectious diseases with major health and socio-economic impact.
      Current understanding of the immune response triggered during infection with
      pathogens causing malaria, hepatitis C and AIDS emphasizes the importance of
      cytotoxic T lymphocytes (CTLs) in combating these infections. This has led to the
      development of new vaccination strategies, some of which are in phase I/II
      clinical trials. Promising strategies of vaccination are based on highly
      attenuated viral vectors, such as Vaccinia virus (VV) in combination with
      heterologous like vectors naked DNA, referred to as priming/booster vaccination.
      While these immunization schedules increased the production of specific CTLs,
      there is a need to further expand the CD8+T cell population to control an
      infection. Among molecules that play a significant role in the modulation of the
      CTL response is the cytokine IL-12. Immunoregulation by IL-12 is of central
      importance in cell-mediated immunity (CMI) against those pathogens and tumors
      that are controlled by cell-mediated mechanisms, supported by Thl cells. The use
      of this cytokine in combination with highly immunogenic VV-derived vectors is a
      promising system for development of future vaccination schedules. In this review,
      we summarize recent data on the use of IL-12 in vaccination procedures, as well
      as undesired side-effects of the cytokine that can be overcome by accurate use of
      dose, route and time-window administration of IL-12 encoding vectors. Results
      described here indicate that VV IL-12-mediated enhancement of the specific CMI
      response against a model antigen HIV-1 env was time- and dose-dependent and that
      the antigen and the cytokine could be expresed from two different rVVs modulating
      the doses of the vectors and allowing for enhancement of a specific CMI response.
      Moreover, the use of IL-12 during DNA prime/VV boost regimens enhanced the
      specific anti-HIV-1 env cellular response 20 times compared to that generated
      after a single rVVenv inoculation. Variables such as: a) dose of the cytokine
      applied, b) time of its administration and c) routes of inoculation play a
      critical role in the final outcome of the response. The findings presented here
      can be extended to other antigens, suggesting that immunomodulatory cytokines can
      be useful in the development of the future vaccines against numerous infectious
      diseases and tumors.

PMID- 11332722
TI  - Human skin reconstruct models: a new application for studies of melanocyte and
      melanoma biology.
AB  - Studies of melanocyte and melanoma biology using monocultures of cells are
      limited because of culture-induced morphology changes and expression of genes
      related to growth, migration, and invasion, which do not reflect the in situ
      phenotype of normal melanocytes, nevus cells, or melanoma cells from biologically
      early progression stages. The development of organotypic cultures of human skin,
      in which culture artifacts are greatly diminished and cell-matrix and cell-cell
      interactions between different cell types can be investigated in a three
      dimensional system, has opened a new era for melanoma research. Long-term in vivo
      studies, especially important for melanomagenesis and melanoma metastasis have
      become possible through grafting of skin reconstructs to immunodeficient
      laboratory animals. In this review, principles and different methods of skin
      reconstruction are introduced with focus on the application for pigment cell
      biology.

PMID- 11332723
TI  - Rsv1-mediated resistance against soybean mosaic virus-N is hypersensitive
      response-independent at inoculation site, but has the potential to initiate a
      hypersensitive response-like mechanism.
AB  - Rsv1, a single dominant gene in soybean PI 96983, confers resistance to most
      strains of Soybean mosaic virus (SMV), including strain G2. The phenotypic
      response includes the lack of symptoms and virus recovery from mechanically
      inoculated leaves. To study the resistance mechanism, SMV-N (an isolate of strain
      G2) was introduced into PI 96983 by grafting. Hypersensitive response (HR)-like
      lesions occurred on the stems, petioles, and leaf veins, and virus was recovered
      from these lesions. The response demonstrated the cytological and histological
      characteristics of HR as well as elevated transcription of a soybean salicylic
      acid-inducible, pathogenesis-related (PR-1) protein gene. Mechanical inoculation
      of PI 96983 primary leaves with a high level of SMV-N virions caused no symptoms
      or up regulation of the PR-1 protein gene transcript. Furthermore, inoculation
      with infectious viral RNA did not alter the resistance phenotype. The data
      suggest that interaction of SMV-N with Rsv1 has the potential to induce an HR
      like defense reaction. Rsv1-mediated resistance in the inoculated leaf, however,
      is HR-independent and operates after virion disassembly.

PMID- 11332724
TI  - The plant pathogen Rhodococcus fascians colonizes the exterior and interior of
      the aerial parts of plants.
AB  - Rhodococcus fascians is a plant-pathogenic bacterium that causes malformations on
      aerial plant parts, whereby leafy galls occur at axillary meristems. The
      colonization behavior on Nicotiana tabacum and Arabidopsis thaliana plants was
      examined. Independent of the infection methods, R. fascians extensively colonized
      the plant surface where the bacteria were surrounded by a slime layer. R.
      fascians caused the collapse of epidermal cells and penetrated intercellularly
      into the plant tissues. The onset of symptom development preceded the extensive
      colonization of the interior. The meristematic regions induced by pathogenic
      strain D188 were surrounded by bacteria. The nonpathogenic strain, D188-5,
      colonized the exterior of the plant equally well, but the linear plasmid
      (pFiD188) seemed to be involved in the penetration efficiency and colonization of
      tobacco tissues.

PMID- 11332725
TI  - Cell-cycle, phase-specific activation of Maize streak virus promoters.
AB  - It is believed that geminiviral DNA replication is coupled to the cell-cycle
      regulatory complex of the plant cell and that the virus-early (complementary or C
      sense) gene products REP and REPA may be able to manipulate the regulation of the
      cycle. In this study, we examined expression from the promoters of Maize streak
      virus (MSV) in transgenic maize plants and cells to determine whether they showed
      cell-cycle specificity. Histochemical staining of plant roots containing "long
      and short" C-sense promoter sequences upstream of the GUS (beta-glucuronidase)
      reporter gene showed that promoter activity was restricted to the meristematic
      region of the roots and was enhanced by 2,4-dichlorophenoxy acetic acid (2,4-D)
      treatment. Analysis of reporter gene and cell-cycle-specific gene transcript
      levels coupled with flow cytometric data in synchronized transgenic maize cells
      revealed that all of the MSV promoters showed cell-cycle specificity. The coat
      protein gene promoter showed highest activity in early G2, whereas the C-sense
      promoter sequences produced two peaks of activity in the S and G2 cell-cycle
      phases.

PMID- 11332726
TI  - Isolation and characterization of a symbiosis-regulated ras from the
      ectomycorrhizal fungus Laccaria bicolor.
AB  - Ectomycorrhizae formed by the symbiotic interaction between ectomycorrhizal fungi
      and plant roots play a key role in maintaining and improving the health of a wide
      range of plants. Mycorrhizal initiation, development, and functional maintenance
      involve morphological changes that are mediated by activation and suppression of
      several fungal and plant genes. We identified a gene, Lbras, in the
      ectomycorrhizal fungus Laccaria bicolor that belongs to the ras family of genes,
      which has been shown in other systems to be associated with signaling pathways
      controlling cell growth and proliferation. The Lbras cDNA complemented ras2
      function in Saccharomyces cerevisiae and had the ability to transform mammalian
      cells. Expression of Lbras, present as a single copy in the genome, was dependent
      upon interaction with host roots. Northern analysis showed that expression was
      detectable in L bicolor 48 h after interaction as well as in the established
      mycorrhizal tissue. Phylogenetic analysis with other Ras proteins showed that
      Lbras is related most closely to Aras of Aspergillus nidulans.

PMID- 11332727
TI  - Genetic mapping and functional analysis of the tomato Bs4 locus governing
      recognition of the Xanthomonas campestris pv. vesicatoria AvrBs4 protein.
AB  - Xanthomonas campestris pv. vesicatoria is the causal agent of bacterial spot
      disease on pepper (Capsicum spp.) and tomato (Lycopersicon spp.). Analysis of 17
      different Lycopersicon accessions with avrBs4-expressing X. campestris pv.
      vesicatoria strains identified 15 resistant and two susceptible tomato genotypes.
      Genetic analysis revealed that AvrBs4 recognition in tomato is governed by a
      single locus, designated Bs4 (bacterial spot resistance locus no. 4). Amplified
      fragment length polymorphism and bulked DNA templates from resistant and
      susceptible plants were used to define a 2.6-cM interval containing the Bs4
      locus. A standard tomato mapping population was employed to localize Bs4-linked
      markers on the short arm of chromosome 5. Investigation of X. campestris pv.
      vesicatoria hrp mutant strains revealed that AvrBs4 secretion and avirulence
      activity are hrp dependent. Agrobacterium-based delivery of the avrBs4 gene into
      tomato triggered a plant response that phenotypically resembled the
      hypersensitive response induced by avrBs4-expressing X. campestris pv.
      vesicatoria strains, suggesting symplastic perception of the avirulence protein.
      Mutations in the avrBs4 C-terminal nuclear localization signals (NLSs) showed
      that NLSs are dispensable for Bs4-mediated recognition. Our data suggest that
      tomato Bs4 and pepper Bs3 employ different recognition modes for detection of the
      highly homologous X. campestris pv. vesicatoria avirulence proteins AvrBs4 and
      AvrBs3.

PMID- 11332728
TI  - Polymorphism of the polyketide synthase gene phID in biocontrol fluorescent
      pseudomonads producing 2,4-diacetylphloroglucinol and comparison of PhID with
      plant polyketide synthases.
AB  - Many biocontrol fluorescent pseudomonads can protect plants from soilborne fungal
      pathogens through production of the antifungal secondary metabolite 2,4
      diacetylphloroglucinol (Phl). One of the phl biosynthetic genes, phlD, encodes a
      polyketide synthase similar to plant chalcone synthases. Here, restriction
      analysis of phlD from 39 Phl+ biocontrol fluorescent pseudomonads yielded seven
      different banding patterns. The gene was sequenced in seven strains, representing
      the different restriction patterns. Cluster analysis of phlD restriction data or
      phlD sequences indicated that phlD polymorphism was high, and two main clusters
      were obtained when predicted PhlD sequences were compared. When the seven PhlD
      sequences were studied with those of other procaryotic polyketide synthases (gram
      positive bacteria) and plant chalcone synthases, however, Phl+ pseudomonads, gram
      positive bacteria, and plants clustered separately. Yet, sequence analysis of
      active site regions for PhlD and plant chalcone synthases revealed that PhlD can
      be considered a member of the chalcone synthase family, which may be interpreted
      as convergent evolution of key enzymes involved in secondary metabolism. For the
      39 Phl+ pseudomonads, a relationship was found among phlD restriction patterns,
      phylogenetic groups defined by 16S rDNA restriction analysis (confirmed by 16S
      rDNA sequencing), and production levels of Phl in vitro.

PMID- 11332729
TI  - Molecular characterization of a subtilase from the vascular wilt fungus Fusarium
      oxysporum.
AB  - The gene prt1 was isolated from the tomato vascular wilt fungus Fusarium
      oxysporum f. sp. lycopersici, whose predicted amino acid sequence shows
      significant homology with subtilisin-like fungal proteinases. Prt1 is a single
      copy gene, and its structure is highly conserved among different formae speciales
      of F. oxysporum. Prt1 is expressed constitutively at low levels during growth on
      different carbon and nitrogen sources and strongly induced in medium containing
      collagen and glucose. As shown by reverse transcription-polymerase chain reaction
      and fluorescence microscopy of F. oxysporum strains carrying a prt1-promoter
      green fluorescent protein fusion, prt1 is expressed at low levels during the
      entire cycle of infection on tomato plants. F. oxysporum strains transformed with
      an expression vector containing the prt1 coding region fused to the inducible
      endopolygalacturonase pg1 gene promoter and grown under promoter-inducing
      conditions secreted high levels of extracellular subtilase activity that resolved
      into a single peak of pI 4.0 upon isoelectric focusing. The active fraction
      produced two clearing bands of 29 and 32 kDa in sodium dodecyl sulfate gels
      containing gelatin. Targeted inactivation of prt1 in F. oxysporum f. sp.
      lycopersici had no detectable effect on mycelial growth, sporulation, and
      pathogenicity on tomato plants.

PMID- 11332730
TI  - Lectin-like glycoprotein PsNLEC-1 is not correctly glycosylated and targeted in
      boron-deficient pea nodules.
AB  - Symbiosome development was studied in pea root nodules from plants growing in the
      absence of boron (B). Rhizobia released into the host cells of nodules from B
      deficient plants developed to abnormal endophytic forms with an altered
      electrophoretic lipopolysaccharide pattern. Immunostaining after sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis and electroblotting of nodule
      homogenates with antibodies that recognize glycoprotein components showed that
      two previously described lectin-like glycoproteins (PsNLEC-1A and PsNLEC-1B) did
      not harbor the carbohydrate epitope normally recognized by specific monoclonal
      antibodies. Material derived from B-deficient nodules, however, still contained
      three antigenic isoforms with similar electrophoretic mobilities to PsNLEC-1
      isoforms A, B, and C. These could be detected following immunoblotting and
      immunostaining with a specific antiserum originating from the purified PsNLEC
      protein that had been heterologously expressed in Escherichia coli. Immunogold
      localization of PsNLEC-1 sugar epitopes in B-deficient nodules showed that they
      were associated mostly with cytoplasmic vesicles rather than normal localization
      in the symbiosome compartment of mature infected cells. These results suggest
      that a modification of the glycosyl-moieties of PsNLEC-1 and an alteration of
      vesicle targeting occur during the development of pea nodules in the absence of
      B, and that these changes are associated with the development of aberrant
      nonfunctional symbiosomes.

PMID- 11332731
TI  - Gain of virulence caused by insertion of a Pot3 transposon in a Magnaporthe
      grisea avirulence gene.
AB  - The avirulence gene AVR-Pita in Magnaporthe grisea prevents the fungus from
      infecting rice cultivars carrying the disease resistance gene Pi-ta. Insertion of
      Pot3 transposon into the promoter of AVR-Pita caused the gain of virulence toward
      Yashiro-mochi, a rice cultivar containing Pi-ta, which demonstrated the ability
      of Pot3 to move within the M. grisea genome. The appearance of Pot3 in M. grisea
      seems to predate the diversification of various host-specific forms of the
      fungus.

PMID- 11332732
TI  - Characterization of the ToxB gene from Pyrenophora tritici-repentis.
AB  - The ToxB gene was cloned and characterized from a race 5 isolate of Pyrenophora
      tritici-repentis from North Dakota. ToxB contains a 261-bp open reading frame
      that encodes a 23 amino acid putative signal peptide and a 64 amino acid host
      selective toxin, Ptr ToxB. Analysis of Ptr ToxB from heterologous expression in
      Pichia pastoris confirms that ToxB encodes a host-selective toxin.

PMID- 11332733
TI  - Rhizobium sp. BR816 produces a complex mixture of known and novel
      lipochitooligosaccharide molecules.
AB  - Rhizobial lipochitooligosaccharide (LCO) signal molecules induce various plant
      responses, leading to nodule development. We report here the LCO structures of
      the broadhost range strain Rhizobium sp. BR816. The LCOs produced are all
      pentamers, carrying common C18:1 or C18:0 fatty acyl chains, N-methylated and C-6
      carbamoylated on the nonreducing terminal N-acetylglucosamine and sulfated on the
      reducing/terminal residue. A second acetyl group can be present on the
      penultimate N-acetylglucosamine from the nonreducing terminus. Two novel
      characteristics were observed: the reducing/terminal residue can be a
      glucosaminitol (open structure) and the degree of acetylation of this
      glucosaminitol or of the reducing residue can vary.

PMID- 11332734
TI  - Identification of defense-related rice genes by suppression subtractive
      hybridization and differential screening.
AB  - Identification of host genes involved in defense responses is one of most
      critical steps leading to the elucidation of disease resistance mechanisms in
      plants. In this study, two different cloning strategies were employed to identify
      defense-related genes from a tropical japonica rice cultivar (Oryza sativa cv.
      Drew). With the use of bacterial colony arrays, differential screening of a blast
      fungus (Pyricularia grisea)-induced rice cDNA library led to the isolation of 22
      distinct rice genes that are expressed differentially in response to blast
      infection. Sequence analysis indicates that most of them are full-length cDNAs
      encoding pathogenesis-related proteins or other relatively abundant proteins. In
      combination with treatments of cycloheximide plus jasmonic acid (JA) or
      benzothiadiazole (BTH) in rice seedlings, the polymerase chain reaction-based
      suppression subtractive hybridization also was conducted to search for immediate
      early (IE) defense-related genes whose transcription is independent of de novo
      protein synthesis. The initial screening of only 768 subtracted clones resulted
      in the identification of 34 distinct IE genes that are induced by JA, BTH, and/or
      blast infection. Database searches revealed that these IE genes encode putative
      mitogen-activated protein kinase, diacylglycerol kinase, zinc finger protein,
      RelA-SpoT protein, ankyrin-containing protein, ABC transporter, beta-ketoacyl-CoA
      synthase, and other potential defense-signaling components. Further
      characterization of these novel IE genes will likely facilitate the elucidation
      of defense signal transduction in rice plants.

PMID- 11332735
TI  - Gap-junctional communication between feeder cells and recipient normal epithelial
      cells correlates with growth stimulation.
AB  - LA7 rat mammary tumor cells stimulate the proliferation, in culture, of three
      normal epithelial cell types, namely mouse mammary, rat mammary, and mouse thymic
      cells. Gap-junctional communication between LA7 feeders and mouse mammary cells
      was demonstrated by microinjection of lucifer yellow, which traveled from LA7 to
      the surrounding mouse mammary cells. The amount of 3H-uridine exchange between
      feeder and recipient mouse mammary, rat mammary, and mouse thymus cells
      correlated with the growth rate induced by the feeders. Cells of the Madin Darby
      canine kidney (MDCK) line, which do not appreciably stimulate mouse mammary cell
      growth when used as feeder cells, also exchange little 3H-uridine with them.
      Expression of connexins Cx43, 32, and 26 was studied in all these cell lines and
      strains by immunocytochemistry. Mouse mammary cells expressed Cx26, and a few
      mouse thymic cells expressed Cx32. LA7, mouse mammary, mouse thymic, and rat
      mammary cells all expressed easily detectable amounts of the gap-junction protein
      Cx43, in contrast to MDCK cells, which expressed only a hint of the protein.
      These results suggest that gap junctions composed of Cx43 are those by which the
      normal epithelial cells communicate with the LA feeders. Thus, the ability of
      feeder cells to stimulate proliferation in recipients correlates with the
      expression of Cx43 in both members of the feeder/recipient pair and the capacity
      to form functional gap junctions between these cells.

PMID- 11332736
TI  - Qualitative and quantitative analysis of monocyte transendothelial migration by
      confocal microscopy and three-dimensional image reconstruction.
AB  - A novel method for qualitative and quantitative analysis of monocyte
      transendothelial migration is described. By labeling monocytes and endothelial
      cells with different fluorophores, and utilizing confocal microscopy and three
      dimensional image reconstruction, transmigrating monocytes were resolved and
      quantified within a subendothelial collagen gel. Comparison of monocyte migration
      across endothelial monolayers derived from human brain microvessels versus
      umbilical veins revealed diapedesis across brain endothelium to be significantly
      delayed. Inclusion of astrocytes within the subendothelial collagen gel resulted
      in the formation of an array of astrocytic processes that simulated the glia
      limitans surrounding brain microvessels in situ, thus yielding a more physiologic
      paradigm of the blood-brain barrier. By virtue of its unique capacity to provide
      information on the total number of migrating cells, this analytic approach
      overcomes significant caveats associated with sampling only aspects of the
      migration process. The potential adaptability of this method to computer-assisted
      analysis further enhances its prospective use in high-throughput screening.

PMID- 11332737
TI  - NASA biotechnology: cell science in microgravity.

PMID- 11332738
TI  - Suppression of antigen-specific lymphocyte activation in modeled microgravity.
AB  - Various parameters of immune suppression are observed in lymphocytes from
      astronauts during and after a space flight. It is difficult to ascribe this
      suppression to microgravity effects on immune cells in crew specimens, due to the
      complex physiological response to space flight and the resultant effect on in
      vitro immune performance. Use of isolated immune cells in true and modeled
      microgravity in immune performance tests, suggests a direct effect of
      microgravity on in vitro cellular function. Specifically, polyclonal activation
      of T-cells is severely suppressed in true and modeled microgravity. These recent
      findings suggest a potential suppression of oligoclonal antigen-specific
      lymphocyte activation in microgravity. We utilized rotating wall vessel (RWV)
      bioreactors as an analog of microgravity for cell cultures to analyze three
      models of antigen-specific activation. A mixed-lymphocyte reaction, as a model
      for a primary immune response, a tetanus toxoid response and a Borrelia
      burgdorferi response, as models of a secondary immune response, were all
      suppressed in the RWV bioreactor. Our findings confirm that the suppression of
      activation observed with polyclonal models also encompasses oligoclonal antigen
      specific activation.

PMID- 11332739
TI  - Modeled microgravity inhibits apoptosis in peripheral blood lymphocytes.
AB  - Microgravity interferes with numerous lymphocyte functions (expression of cell
      surface molecules, locomotion, polyclonal and antigen-specific activation, and
      the protein kinase C activity in signal transduction). The latter suggests that
      gravity may also affect programmed cell death (PCD) in lymphocyte populations. To
      test this hypothesis, we investigated spontaneous, activation- and radiation
      induced PCD in peripheral blood mononuclear cells exposed to modeled microgravity
      (MMG) using a rotating cell culture system. The results showed significant
      inhibition of radiation- and activation-induced apoptosis in MMG and provide
      insights into the potential mechanisms of this phenomenon.

PMID- 11332740
TI  - Proliferation of human hematopoietic bone marrow cells in simulated microgravity.
AB  - Expansion and/or maintenance of hematopoietic stem cell (HSC) potential following
      in vitro culture remains a major obstacle in stem cell biology and bone marrow
      (BM) transplantation. Several studies suggest that culture of mammalian cells in
      microgravity (micro-g) may reduce proliferation and differentiation of these
      cells. We investigated the application of these findings to the field of stem
      cell biology in the hopes of expanding HSC with minimal loss of hematopoietic
      function. To this end, BM CD34+ cells were cultured for 4-6 d in rotating wall
      vessels for simulation of micro-g, and assessed for expansion, cell cycle
      activation, apoptosis, and hematopoietic potential. While CD34+ cells cultured in
      normal gravity (1-g) proliferated up to threefold by day 4-6, cells cultured in
      micro-g did not increase in number. As a possible explanation for this, cells
      cultured in simulated micro-g were found to exit G0/G1 phase of cell cycle at a
      slower rate than 1-g controls. When assayed for primitive hematopoietic potential
      in secondary conventional 1-g long-term cultures, cells from initial micro-g
      cultures produced greater numbers of cells and progenitors, and for a longer
      period of time, than cultures initiated with 1-g control cells. Similar low
      levels of apoptosis and adhesion molecule phenotype in micro-g and 1-g-cultured
      cells suggested similar growth patterns in the two settings. These data begin to
      elucidate the effects of micro-g on proliferation of human hematopoietic cells
      and may be potentially beneficial to the fields of stem cell biology and somatic
      gene therapy.

PMID- 11332742
TI  - Microarray analysis of genes differentially expressed in HepG2 cells cultured in
      simulated microgravity: preliminary report.
AB  - Developed at NASA, the rotary cell culture system (RCCS) allows the creation of
      unique microgravity environment of low shear force, high-mass transfer, and
      enables three-dimensional (3D) cell culture of dissimilar cell types. Recently we
      demonstrated that a simulated microgravity is conducive for maintaining long-term
      cultures of functional hepatocytes and promote 3D cell assembly. Using
      deoxyribonucleic acid (DNA) microarray technology, it is now possible to measure
      the levels of thousands of different messenger ribonucleic acids (mRNAs) in a
      single hybridization step. This technique is particularly powerful for comparing
      gene expression in the same tissue under different environmental conditions. The
      aim of this research was to analyze gene expression of hepatoblastoma cell line
      (HepG2) during early stage of 3D-cell assembly in simulated microgravity. For
      this, mRNA from HepG2 cultured in the RCCS was analyzed by deoxyribonucleic acid
      microarray. Analyses of HepG2 mRNA by using 6K glass DNA microarray revealed
      changes in expression of 95 genes (overexpression of 85 genes and downregulation
      of 10 genes). Our preliminary results indicated that simulated microgravity
      modifies the expression of several genes and that microarray technology may
      provide new understanding of the fundamental biological questions of how gravity
      affects the development and function of individual cells.

PMID- 11332741
TI  - Erythroid cell growth and differentiation in vitro in the simulated microgravity
      environment of the NASA rotating wall vessel bioreactor.
AB  - Prolonged exposure of humans and experimental animals to the altered
      gravitational conditions of space flight has adverse effects on the lymphoid and
      erythroid hematopoietic systems. Although some information is available regarding
      the cellular and molecular changes in lymphocytes exposed to microgravity, little
      is known about the erythroid cellular changes that may underlie the reduction in
      erythropoiesis and resultant anemia. We now report a reduction in erythroid
      growth and a profound inhibition of erythropoietin (Epo)-induced differentiation
      in a ground-based simulated microgravity model system. Rauscher murine
      erythroleukemia cells were grown either in tissue culture vessels at 1 x g or in
      the simulated microgravity environment of the NASA-designed rotating wall vessel
      (RWV) bioreactor. Logarithmic growth was observed under both conditions; however,
      the doubling time in simulated microgravity was only one-half of that seen at 1 x
      g. No difference in apoptosis was detected. Induction with Epo at the initiation
      of the culture resulted in differentiation of approximately 25% of the cells at 1
      x g, consistent with our previous observations. In contrast, induction with Epo
      at the initiation of simulated microgravity resulted in only one-half of this
      degree of differentiation. Significantly, the growth of cells in simulated
      microgravity for 24 h prior to Epo induction inhibited the differentiation almost
      completely. The results suggest that the NASA RWV bioreactor may serve as a
      suitable ground-based microgravity simulator to model the cellular and molecular
      changes in erythroid cells observed in true microgravity.

PMID- 11332743
TI  - Response to Gavarito, Z. V.; Muneton, V. C.; Sutachan, J. J.; Hurtado, H. Is S
      100 protein a suitable marker for adult Schwann cells? (In Vitro Cell. Dev. Biol.
      36a:281-283; 2000).

PMID- 11332744
TI  - In vitro and in vivo effects of a fat body extract on Spodoptera littoralis.

PMID- 11332745
TI  - Nongenomic vitamin D3 analogs activating ERK2 in HL-60 cells show that retinoic
      acid-induced differentiation and cell cycle arrest require early concurrent MAPK
      and RAR and RXR activation.

PMID- 11332746
TI  - Digital imaging considerations for gel electrophoresis analysis systems.
AB  - Gel analysis system purchasers have a large variety of digital imaging products
      to choose from today. Understanding the specifications presented by the
      manufacturers is important to ensure that the system fits the needs ofthe
      researcher using the system. The background information contained in this paper
      explains the terminology and many of the specifications along with their
      significance.

PMID- 11332747
TI  - Imaging and detection technologies for image analysis in electrophoresis.
AB  - Image capture is the first step of image analysis. There are two major devices
      for image capture in the field of electrophoresis. One is the charged-couple
      device (CCD) camera and the other is the scanner. Image capture technologies have
      shown great progress in recent years especially in the field of fluorescence
      detection and chemiluminescent detection. The direction of image analysis is high
      resolution, wide dynamic range and high density precision and this holds true for
      the CCD camera system. Various components in the CCD camera system suitable for
      high-sensitive fluorescence detection and chemiluminescent detection are
      explained. As an example, the LAS-1000plus camera system which has 1364 x 922
      pixels and generates 14-bits image is introduced. Powerful cooling enables
      overnight exposure of chemiluminescence. Introduction of blue light-emitting
      diode (LED) as excitation light source improved safety to eyes. Two types of
      scanners for fluorescence detection and the specific characteristics are
      explained. There are mechanical scanning systems using confocal optics and
      optical scanning systems using light collecting guide optics. Deep focusing range
      and equal fluorescence intensity at various depth is a characteristic feature of
      light collecting guide optics.

PMID- 11332748
TI  - A whole new way of looking at things: the use of Dark Reader technology to detect
      fluorophors.
AB  - The Dark Reader optical system (Clare Chemical Research, Denver, CO, USA) uses
      relatively low intensity broad-band visible blue light in combination with broad
      band optical filters to detect fluorescence with a level of sensitivity that
      often surpasses that of UV transilluminators and can rival that of laser-based
      scanners. Applications of DR (Clare Chemical Research) devices include the
      detection of DNA and SYBR-stained protein samples following, and also during,
      electrophoresis. Unlike laser-based imaging systems, the fluorescence is directly
      visible to the user as well as being fully compatible with charge-coupled device
      (CCD) and Polaroid camera-based detection and imaging. Additionally, the DR
      optical system functions well in multicolor fluorophor environments. Because the
      Dark Reader does not emit any UV light, the extent of DNA damage incurred when
      visualizing DNA samples is drastically reduced compared to the damage produced by
      a UV device and this can have a significant benefit on downstream cloning
      protocols. Furthermore, dye photobleaching is minimal, extending the length of
      time that a fluorescent sample is visible. The inherent flexibility of the DR
      optical system allows many different configurations of the Dark Reader to be
      constructed such as transilluminators, hand lamps and integrated transilluminator
      electrophoresis units.

PMID- 11332749
TI  - A unique charge-coupled device/xenon arc lamp based imaging system for the
      accurate detection and quantitation of multicolour fluorescence.
AB  - In recent years the use of fluorescent dyes in biological applications has
      dramatically increased. The continual improvement in the capabilities of these
      fluorescent dyes demands increasingly sensitive detection systems that provide
      accurate quantitation over a wide linear dynamic range. In the field of
      proteomics, the detection, quantitation and identification of very low abundance
      proteins are of extreme importance in understanding cellular processes.
      Therefore, the instrumentation used to acquire an image of such samples, for spot
      picking and identification by mass spectrometry, must be sensitive enough to be
      able, not only, to maximise the sensitivity and dynamic range of the staining
      dyes but, as importantly, adapt to the ever changing portfolio of fluorescent
      dyes as they become available. Just as the available fluorescent probes are
      improving and evolving so are the users application requirements. Therefore, the
      instrumentation chosen must be flexible to address and adapt to those changing
      needs. As a result, a highly competitive market for the supply and production of
      such dyes and the instrumentation for their detection and quantitation have
      emerged. The instrumentation currently available is based on either
      laser/photomultiplier tube (PMT) scanning or lamp/charge-coupled device (CCD)
      based mechanisms. This review briefly discusses the advantages and disadvantages
      of both System types for fluorescence imaging, gives a technical overview of CCD
      technology and describes in detail a unique xenon/are lamp CCD based instrument,
      from PerkinElmer Life Sciences. The Wallac-1442 ARTHUR is unique in its ability
      to scan both large areas at high resolution and give accurate selectable
      excitation over the whole of the UV/visible range. It operates by filtering both
      the excitation and emission wavelengths, providing optimal and accurate
      measurement and quantitation of virtually any available dye and allows excellent
      spectral resolution between different fluorophores. This flexibility and
      excitation accuracy is key to multicolour applications and future adaptation of
      the instrument to address the application requirements and newly emerging dyes.

PMID- 11332750
TI  - Fluorescent imaging and analysis with Typhoon 8600.
AB  - Current technologies in laser-based imaging systems for life science applications
      offer highly sensitive and quantitative detection of multiple labels. Typhoon
      8600 variable mode imager is capable of fluorescence, storage phosphor, and
      chemiluminescence detection of gels and blots. The system delivers sensitive
      fluorescent detection of nucleic acids and proteins in both agarose and
      polyacrylamide gel formats. Detection and discrimination of multicolor
      fluorescent signals in fragment analysis, electromobility shift assays, Western
      blotting and other applications enhance the speed and accuracy of analysis.

PMID- 11332751
TI  - Quantifying DNA damage by gel electrophoresis, electronic imaging and number
      average length analysis.
AB  - DNA damages that can be converted to single- or double strand breaks can be
      quantified by separating DNA by gel electrophoresis and obtaining a quantitative
      image of the resulting distribution of DNA in the gel. We review the theory of
      this method and discuss its implementation, including the charge-coupled device
      (CCD) camera systems we developed to acquire images of fluorophore labeled DNA.

PMID- 11332752
TI  - Counterion-dye staining method for DNA in agarose gels using crystal violet and
      methyl orange.
AB  - Sensitive and safe methods for visualization of DNA in agarose gels are
      described. 0.001% crystal violet dissolved in distilled water was used for DNA
      staining on agarose gels and it could detect as little as 16 ng of DNA (3 kb,
      pGem-7Zf/EcoRI) without destaining procedure. The detection limit is four times
      lower than that of ethidium bromide. To improve the sensitivity, we studied a
      counterion-dye staining method using methyl orange as a counterion-dye which
      contributes to reduce excessive background staining by crystal violet. Dye
      concentration, pH of staining solution, mixing molar ratio of two dyes, and
      staining times were optimized for the counterion-dye staining. By the staining
      with a mixed solution of 0.0025% crystal violet and 0.0005% methyl orange in
      distilled water, 8 ng of the 3 kb DNA in an agarose gel was detected within 30
      min.

PMID- 11332753
TI  - Factors affecting quantitation of DNA bands in gels using a charge-coupled device
      imaging system.
AB  - Quantitation of DNA bands separated in polyacrylamide or agarose gels was tested
      under a variety of conditions to examine key factors contributing to the ability
      to obtain quantitative data. Variations tested included comparison of different
      fluorescent stains (ethidium bromide and GelStar stain), and variations of other
      parameters relating to the electrophoretic separation, e.g. gel and sample
      geometry, mode of staining, and mode of excitation of stains. The results showed
      that linear results were seen for a similar 20-30-fold range of DNA
      concentrations with both stains tested and that it is critical to standardize
      separations to obtain consistent results. Variations in separation and detection
      could lead to relatively large changes in fluorescent signals seen for similar
      amounts of DNA.

PMID- 11332754
TI  - Detection of biomolecules in electrophoresis gels with salts of imidazole and
      zinc II: a decade of research.
AB  - The proven ability of gel electrophoresis to simultaneously resolve, in a single
      experiment, many components from complex biological samples, has determined its
      preference over a variety of well-established chromatographic methods. Therefore,
      procedures placed at the interface between gel separation and microanalysis have
      earned increasing significance with respect to the overall success of the
      microanalytical strategy. The first of these procedures is the detection
      technique. The most important requirement for compatibility with further analysis
      or bioapplications is that the staining method does not compromise the chemical
      integrity and the biological properties of micropurified biomolecules. Procedures
      for negative detection of proteins with metal salts that have been proven to
      comply with this condition have been known for about 15 years. Only recently have
      these procedures been extended to the field of nucleic acids and
      lipopolysaccharides. The focus of this review is to chronicle the development and
      current status of the negative or reverse stain procedure based on the in-gel
      reaction of imidazole with zinc salts and its applications forthe
      micropurification and analysis of unmodified proteins, nucleic acids and
      bacterial lipopolysaccharides. We highlight the common aspects in the detection
      of the three types of biomolecules, and their applications to structural and
      biological analyses. Emphasis is given on the mechanism underlying imidazole-zinc
      staining, as it contributes to a deeper understanding of a general detection
      mechanism with metal salts. Finally, we discuss the latest applications of the
      techniques in proteomics and their possible impact on the characterization of gel
      separated single components from complex lipopolysaccharides.

PMID- 11332755
TI  - Fluorescent labeling of proteins with nile red and 2-methoxy-2,4-diphenyl-3(2H)
      furanone: physicochemical basis and application to the rapid staining of sodium
      dodecyl sulfate polyacrylamide gels and Western blots.
AB  - The fluorescent hydrophobic dye Nile red allows the rapid, sensitive, and general
      staining of proteins in sodium dodecyl sulfate (SDS)-polyacrylamide gels. Nile
      red staining does not preclude further electroblotting of protein bands onto
      polyvinylidene difluoride (PVDF) membranes. The resulting Western blot can be
      stained with the covalent fluorescent dye 2-methoxy-2,4-diphenyl-3(2H)-furanone
      (MDPF) using a simple procedure. MDPF staining allows further N-terminal
      microsequencing and immunodetection of specific bands. This review considers the
      physicochemical, structural, and analytical studies that have led to the
      development of Nile red and MDPF staining methods. The usefulness of these
      procedures is discussed in comparison to other currently available fluorescent
      and nonfluorescent protein detection methods.

PMID- 11332756
TI  - An improved, luminescent europium-based stain for detection of electroblotted
      proteins on nitrocellulose or polyvinylidene difluoride membranes.
AB  - SYPRO Rose Plus protein blot stain is an improved europium-based metal chelate
      stain for the detection of proteins on nitrocellulose and poly(vinylidene
      difluoride) (PVDF) membranes. Staining is achieved without covalently modifying
      the proteins. The stain may be excited with a 254 nm (UV-C), 302 nm (UV-B), or
      365 nm (UV-A) light source and displays a sharp emission maximum at 612 nm. The
      emission peak has a full width at half-maximum of only 8 nm. The stain exhibits
      exceptional photostability, allowing long exposure times for maximum sensitivity.
      Since the dye is composed of a europium complex, it has a long emission lifetime,
      potentially allowing time-resolved detection, greatly reducing background
      fluorescence. Proteins immobilized to a nitrocellulose or PVDF membrane by
      electroblotting, dot-blotting, or vacuum slot-blotting are incubated with SYPRO
      Rose Plus protein blot stain for 15-30 min. Membranes are rinsed briefly,
      visualized with UV epi-illumination and the luminescence of the europium dye is
      measured using a 490 nm long-pass or 625 +/- 15 nm band-pass filter in
      combination with a conventional photographic or charge-coupled device (CCD)
      camera system. Alternatively, the dye may be visualized using a xenon-arc
      illumination source. The stain is readily removed from proteins by incubating
      membranes at mildly alkaline pH. The reversibility of the protein staining
      procedure allows for subsequent biochemical analyses, such as immunoblotting and
      biotin-streptavidin detection using colorimetric, direct fluorescence or
      fluorogenic visualization methods.

PMID- 11332757
TI  - Charge-coupled device camera-based detection of fluorescence-labeled proteins
      immobilized on nitrocellulose membranes.
AB  - Proteins dotted on nitrocellulose membranes are biotinylated by reaction with a
      biotinyl-succinimide ester. The resulting biotinyl residues serve as specific
      binding sites for a subsequent streptavidin-based detection system. Using
      streptavidin-peroxidase, the proteins are visualized either by deposition of a
      colored formazan dye or by enhanced chemiluminescence the latter being twofold
      more sensitive. Alternatively, streptavidin-fluorescein isothiocyanate (FITC) is
      substituted for the peroxidase conjugate as tool for protein staining. The
      sensitivity of both staining variants is dramatically improved by the inclusion
      of the reporter deposition technique. The fluorescence-labeled proteins are
      visualized on a visible blue light emitting illuminator preventing the bothering
      effect of photobleaching. In combination with a charge-coupled device (CCD)
      camera-based image analyzing system the established stain with streptavidin-FITC
      detects about 10 pg of protein dot blotted on nitrocellulose membranes.

PMID- 11332758
TI  - Green/red dual fluorescence detection of total protein and alkaline phosphate
      conjugated probes on blotting membranes.
AB  - A two-color fluorescence detection method is described based upon covalently
      coupling the succinimidyl ester of BODIPY FL-X to proteins immobilized on
      poly(vinylidene difluoride) (PVDF) membranes, followed by detection of target
      proteins using the fluorogenic substrate 9H-(1,3-dichloro-9,9-dimethylacridin-2
      one-7-yl(DDAO)-phosphate in combination with alkaline-phosphatase-conjugated
      reporter molecules. This results in all proteins in the profile being visualized
      as green signal while those detected specifically with the alkaline-phosphatase
      conjugate appear as red signal. The dichromatic detection system is broadly
      compatible with a wide range of analytical imaging devices including UV epi- or
      transilluminators combined with photographic or charge-coupled device (CCD)
      cameras, xenon-arc sources equipped with appropriate excitation/emission filters,
      and dual laser gel scanners outfitted with a 473 nm second-harmonic generation or
      488 nm argon-ion laser as well as a 633 nm helium-neon or 635 nm diode laser. The
      dichromatic detection method permits detection of low nanogram amounts of protein
      and allows for unambiguous identification of target proteins relative to the
      entire protein profile on a single electroblot, obviating the need to run
      replicate gels that would otherwise require visualization of total proteins by
      silver staining and subsequent alignment with chemiluminescent or colorimetric
      signals generated on electroblots.

PMID- 11332759
TI  - Mass spectrometry compatibility of two-dimensional gel protein stains.
AB  - As proteomic technology evolves, protein staining sensitivity is constantly being
      improved, enabling researchers to better visualize the proteome of their system.
      The current challenge is to balance the limits of detection of protein
      visualization with those of the mass spectrometric methods. In this report, mass
      spectra generated from human serum or rat liver proteins stained with either
      colloidal Coomassie blue, Daiichi silver, SYPRO Orange, SYPRO Red, SYPRO Ruby, or
      SYPRO Tangerine are compared. It has been concluded that the newest generation of
      fluorescent protein stains, compared with traditional staining methods, are more
      compatible to matrix-assisted laser desorption/ionization (MALDI) and liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) methods. The number of
      database matches obtained using each mass spectrometry method and the percent
      sequence coverage obtained from trypsin digested proteins stained using these six
      methods is provided.

PMID- 11332760
TI  - Practical aspects of fluorescent staining for proteomic applications.
AB  - SYPRO Orange and SYPRO Ruby staining methods, modified for use with large-format
      two dimensional (2-D) gels, are compared to the manufacturer's recommended
      protocols to determine sensitivity and reproducibility of the new methods. This
      study examines the critical aspects of fixation, washing, and staining to develop
      an optimized fluorescent staining method. It was determined that careful control
      of sodium dodecyl sulfate (SDS) levels and pH in the gel was critical for
      successful staining with SYPRO Orange. Overnight fixation in 40% ethanol/2%
      acetic acid/0.0005% SDS preserved protein content, eliminated ampholyte-generated
      staining artifacts, and had no detrimental effects on staining. Three one-hour
      washes in 2% acetic acid/0.0005% SDS, followed by staining with SYPRO Orange
      diluted 1:5,000 with washing solution for 3 or more hours, produced high
      sensitivity, low background images using a STORM 860 laser scanner. Gels viewed
      two years after staining showed no significant changes with respect to the
      initial protein patterns, and allowed successful mass spectrometric postgel
      characterization of protein spots. Protocol changes applied to SYPRO Ruby
      staining improved the contrast of STORM 860-generated images, but had little
      impact on staining sensitivity. A comparison of the cost benefits of staining
      with SYPRO Orange vs. SYPRO Ruby is also discussed.

PMID- 11332761
TI  - Mass spectrometric imaging of immobilized pH gradient gels and creation of
      "virtual" two-dimensional gels.
AB  - We have developed a matrix assisted laser desorption/ionization-time of flight
      (MALDI-TOF) based technique for the detection of intact proteins directly from
      immobilized pH gradient gels (IPGs). The use of this technique to visualize
      proteins from IPGs was explored in this study. Whole cell Escherichia coli
      extracts of various loadings were separated on IPGs. These IPGs were processed to
      remove contaminants and to achieve matrix/analyte cocrystallization on the
      surface of the gel. Mass spectra were acquired by scanning the surface of the gel
      and were assimilated into a "virtual" two dimensional (2-D) gel. This virtual 2-D
      gel is analogous to a "classical" 2-D gel, except that the molecular weight
      information is acquired by mass spectrometry rather than by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). This mass spectrometry
      (MS) based technology exemplifies a number of desirable characteristics, some of
      which are not attainable with classical two-dimensional electrophoresis (2-DE).
      These include high sensitivity, high reproducibility, and an inherently higher
      resolution and mass accuracy than 2-D gels. Furthermore, there is a difference in
      selectivity exhibited between virtual 2-D gels and classical 2-D gels, as a
      number of proteins are visible in the virtual gel image that are not present in
      the stained gels and vice versa. In this report, virtual 2-D gels will be
      compared to classical 2-D gels to illustrate these features.

PMID- 11332762
TI  - Clinical application of a rapid method using agarose gel electrophoresis and
      Western blotting to evaluate von Willebrand factor protease activity.
AB  - A method for evaluating the activity of the von Willebrand factor (vWF) protease
      is described, and a clinical application is illustrated. The procedure utilizes
      gel electrophoresis, Western blotting, and luminographic detection methods to
      evaluate the distribution of vWF multimers before and after incubation of
      clinical samples under conditions that favor proteolysis by this enzyme.
      Physiologically, the high-molecular-weight multimers of vWF are cleaved by the
      vWF protease under conditions of high shear stress in parts of the arterial
      circulation; cleavage of vWF multimers is also observed after exposure of vWF to
      denaturing agents in vitro and thus can serve as a laboratory test for the
      activity of the protease. vWF protease activity is decreased or absent in
      patients with thrombotic thrombocytopenic purpura due to an inhibiting
      autoantibody, and this leads to high levels of noncleaved vWF and to life
      threatening thrombosis, thrombocytopenia and anemia. The assay evaluates the
      activity of the protease by assessing the cleavage of vWF multimers after patient
      plasmas are incubated in vitro under denaturing conditions. With the use of these
      electrophoresis and Western blotting techniques, patient plasmas can be rapidly
      assessed for the activity of the vWF protease which may aid in the treatment
      strategy for these patients.

PMID- 11332763
TI  - A novel subfractionation approach for mitochondrial proteins: a three-dimensional
      mitochondrial proteome map.
AB  - As mitochondria play critical roles in both cell life and cell death, there is
      great interest in obtaining a human mitochondrial proteome map. Such a map could
      potentially be useful in diagnosing diseases, identifying targets for drug
      therapy, and in screening for unwanted drug side effects. In this paper, we
      present a novel approach to obtaining a human mitochondrial proteome map that
      combines sucrose gradient centrifugation with standard two-dimensional gel
      electrophoresis. The resulting three-dimensional separation of proteins allows us
      to address some of the problems encountered during previous attempts to obtain
      mitochondrial proteome maps such as resolution of proteins and solubility of
      hydrophobic proteins during isoelectric focusing. In addition, we show that this
      new approach provides functional information about protein complexes within the
      organelle that is not obtained with two-dimensional gel electrophoresis of whole
      mitochondria.

PMID- 11332764
TI  - Fluorescent Bocillins: synthesis and application in the detection of penicillin
      binding proteins.
AB  - Novel fluorescent analogs of penicillin V were synthesized and evaluated for
      efficacy in the detection of penicillin binding proteins (PBPs). These molecules
      include the full structure of penicillin V, with the potent Bodipy fluorophore
      attached to the para-position of the penicillin V phenyl group. The green
      fluorescent Bocillin FL and the near-infrared (IR) fluorescent Bocillin 650/665
      probes were shown to bind to PBPs, both purified and from membrane preparations,
      with high affinity and specificity. These reagents allow for facile detection of
      2-4 ng of purified PBP with the aid of a fluorescent scanner.

PMID- 11332765
TI  - Reliable quantification of in vitro synthesized green fluorescent protein:
      comparison of fluorescence activity and total protein levels.
AB  - At any time in vitro or in vivo expressed unlabeled proteins have to be
      quantified it is difficult to find a reliable method, especially with nonpurified
      samples. Quantification via protein activity can result in too low levels if the
      proteins analyzed tend to aggregate into inactive forms. Here, wild-type green
      fluorescent protein (GFPwt) was expressed in high amounts in vitro using the
      Rapid Translation System 500 based on Escherichia coli lysates. Fluorescent
      activity was determined in dependence of oxygen and compared to total protein
      levels. In the presence of low amounts of oxygen only 16% of the whole GFPwt
      amounts were detectable via determination of fluorescence activity. A reliable
      method to easily quantify whole protein levels even without specific antibodies
      and without purification steps by simple sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis (SDS-PAGE) and Coomassie blue staining is described.

PMID- 11332766
TI  - Simultaneous, two-color fluorescence detection of total protein profiles and beta
      glucuronidase activity in polyacrylamide gel.
AB  - A dichromatic method for measuring the specific activity of beta-glucuronidase
      from complex cell homogenates or partially purified protein fractions is
      presented. Dual fluorescence is achieved by using the green emitting fluorogenic
      substrate ELF 97 beta-D-glucuronide to detect beta-glucuronidase activity,
      followed by the red emitting SYPRO Ruby protein gel stain or SYPRO Ruby IEF gel
      stain to detect the remaining proteins in the electrophoretic profile. Both ELF
      97 alcohol, the highly fluorescent hydrolytic product generated from the enzyme
      substrate, and the SYPRO Ruby total protein stains are maximally excited by
      ultraviolet illumination. ELF 97 alcohol emits maximally at 525 nm while the
      SYPRO Ruby dyes emit maximally at 610 nm. Since ELF 97 beta-glucuronide is a
      precipitating substrate, it allows precise localization of beta-glucuronidase
      activity with minimal band diffusion. The staining method is simple and direct,
      without the requirement for ancillary coupling reactions. Dichromatic protein
      detection is demonstrated after sodium dodecyl sulfate(SDS)-polyacrylamide gel
      electrophoresis, carrier ampholyte-mediated isoelectric focusing or two
      dimensional gel electrophoresis.

PMID- 11332767
TI  - Neuronal ceroid lipofuscinoses: classification and diagnosis.
AB  - The neuronal ceroid lipofuscinoses (NCLs) are neurodegenerative disorders
      characterized by accumulation of ceroid lipopigment in lysosomes in various
      tissues and organs. The childhood forms of the NCLs represent the most common
      neurogenetic disorders of childhood and are inherited in an autosomal-recessive
      mode. The adult form of NCL is rare and shows either an autosomal-recessive or
      autosomal dominant mode of inheritance. Currently, five genes associated with
      various childhood forms of NCLs, designated CLN1, CLN2, CLN3, CLN5, and CLN8,
      have been isolated and characterized. Two of these genes, CLN1 and CLN2, encode
      lysosomal enzymes: palmitoyl protein thioesterase 1 (PPT1) and tripetidyl
      peptidase 1 (TPP1), respectively. CLN3, CLN5, and CLN8 encode proteins of
      predicted transmembrane topology, whose function has not been characterized yet.
      Two other genes, CLN6 and CLN7, have been assigned recently to small chromosomal
      regions. Gene(s) associated with the adult form of NCLs (CLN4) are at present
      unknown. This study summarizes the current classification and new diagnostic
      criteria of NCLs based on clinicopathological, biochemical, and molecular genetic
      data. Material includes 159 probands with NCL (37 CLNI, 72 classical CLN2, 10
      variant LINCL, and 40 CLN3) collected at the New York State Institute for Basic
      Research in Developmental Disabilities (IBR) as well as a comprehensive review of
      the literature. The results of our study indicate that although only biochemical
      and molecular genetic studies allow for definitive diagnosis, ultrastructural
      studies of the biopsy material are still very useful. Thus, although treatments
      for NCLs are not available at present, the diagnosis has become better defined.

PMID- 11332768
TI  - Positional cloning of the JNCL gene, CLN3.

PMID- 11332769
TI  - Studies of homogenous populations: CLN5 and CLN8.
AB  - Finland and the Finns have been the subject of numerous genetic and genealogical
      studies, owing to enrichment of certain rare hereditary disorders in the Finnish
      population. Two types of NCL have so-far been found almost exclusively in
      Finland: Finnish variant late infantile NCL, vLINCL (CLN5), and the Northern
      epilepsy syndrome or Progressive epilepsy with mental retardation, EPMR (CLN8).
      The first symptoms of Finnish vLINCL are concentration problems or motor
      clumsiness by 3 to 6 years of age, followed by mental retardation, visual
      failure, ataxia, myoclonus, and epilepsy. Northern epilepsy, the newest member of
      the NCL family with the most protracted course, is characterized by the onset of
      generalized seizures between 5 and 10 years of age and subsequent progressive
      mental retardation. Visual problems are slight and late, while myoclonus has not
      been observed. Both the Finnish vLINCL and Northern epilepsy are pathologically
      characterized by intraneuronal cytoplasmic deposits of autofluorescent granules
      which are Luxol fast blue-, PAS-, and Sudan black B-positive in paraffin
      sections. In Northern epilepsy the intraneuronal storage process and neuronal
      destruction are generally of mild degree but highly selective and, in contrast to
      other forms of childhood onset NCL, the cerebellar cortex is relatively spared.
      By electron microscopy the storage bodies mainly contain rectilinear complex type
      and fingerprint profiles in Finnish vLINCL and structures resembling curvilinear
      profiles in Northern epilepsy. Mitochondrial ATP synthase subunit c is the main
      stored protein in both disorders. Both the DCLN5 and CLN8 genes encode putative
      membrane proteins with yet unknown functions. Furthermore, a well studied
      spontaneously occurring autosomal recessive mouse mutant, motor neuron
      degeneration (mnd) mouse, is a homolog for CLN8.

PMID- 11332770
TI  - Molecular genetic testing for neuronal ceroid lipofuscinoses.
AB  - Eight different NCL forms have been recognized to be encoded by genes CLN1-8.
      CLN1,2,3,5,and 8 have been cloned, and at least 85 mutations have been detected.
      Molecular technology can now be applied to genetic testing for NCLs; testing is
      now available in clinic diagnostic and research laboratories for CLN genes that
      have been cloned. Molecular genetic testing makes it possible not only to confirm
      clinical and pathological diagnoses but also to offer pre-symptom diagnosis and
      carrier screening for NCL families. In addition, DNA-based mutation analysis may
      predict prenatal outcome more accurately for pregnant women in NCL families.

PMID- 11332771
TI  - Genetic counseling in the neuronal ceroid lipofuscinoses.

PMID- 11332772
TI  - Neurotrophic factors as potential therapeutic agents in neuronal ceroid
      lipofuscinosis.

PMID- 11332773
TI  - Animal models for the ceroid lipofuscinoses.

PMID- 11332775
TI  - Outlook for future treatment.
AB  - Currently, no treatment is available for neuronal ceroid lipofuscinoses. The
      progress of human genome project will stimulate molecular cloning of unidentified
      genes underlying the NCLs, which will lead eventually clinical management and
      therapies for NCL. Characterizing the native substrate(s) for the palmitoyl
      protein thioesterase-1 (PPT1) and tripeptidyl peptidase 1 (TPP1), understanding
      the protein functions encoded by CLN genes, and uncovering the pathological
      metabolic mechanism for the NCLs are the bases of designing rational treatments
      for the NCLs. Testing potential therapeutic agents, replacing deficient enzymes,
      and developing gene therapy will be the major tasks for NCL researchers.

PMID- 11332774
TI  - Experimental models of NCL: the yeast model.

PMID- 11332776
TI  - Cellular pathology and pathogenic aspects of neuronal ceroid lipofuscinoses.
AB  - Lysosomal accumulation of autofluorescent, ceroid lipopigment material in various
      tissues and organs is a common feature of the neuronal ceroid lipofuscinoses
      (NCLs). However, recent clinicopathologic and genetic studies have evidenced that
      NCLs encompass a group of highly heterogeneous disorders. In five of the eight
      NCL variants distinguished at present, genes associated with the disease process
      have been isolated and characterized (CLN1, CLN2, CLN3, CLN5, CLN8). Only
      products of two of these genes, CLN 1 and CLN2, have structural and functional
      properties of lysosomal enzymes. Nevertheless, according to the nature of the
      material accumulated in the lysosomes, NCLs in humans as well as natural animal
      models of these disorders can be divided into two major groups: those
      characterized by the prominent storage of saposins A and D, and those showing the
      predominance of subunit c of mitochondrial ATP synthase accumulation. Thus,
      taking into account the chemical character of the major component of the storage
      material, NCLs can be classified currently as proteinoses. Of importance,
      although lysosomal storage material accumulates in NCL subjects in various
      organs, only brain tissue shows severe dysfunction and cell death, another common
      feature of the NCL disease process. However, the relation between the genetic
      defects associated with the NCL forms, the accumulation of storage material, and
      tissue damage is still unknown. This chapter introduces the reader to the complex
      pathogenesis of NCLs and summarizes our current knowledge of the potential
      consequences of the genetic defects of NCL-associated proteins on the biology of
      the cell.

PMID- 11332777
TI  - Positional candidate gene cloning of CLN1.
AB  - Mutations in the CLN1 gene encoding palmitoyl-protein thioesterase (PPT) underlie
      the recessive neurodegenerative disorder, infantile Batten disease, or infantile
      neuronal ceroid lipofuscinosis (INCL). The CLN1 gene was mapped to chromosome
      1p32 in the vicinity of a microsatellite marker HY-TM1 in a cohort of Finnish
      INCL families, and mapping of the PPT gene to the CLN1 critical region (and the
      discovery of mutations in PPT in several unrelated families) led to conclusive
      identification of PPT as the disease gene. PPT is a lysosomal thioesterase that
      removes fatty acids from fatty-acylated cysteine residues in proteins. The
      accumulation of fatty acyl cysteine thioesters can be reversed in INCL cells by
      the exogenous administration of recombinant PPT, which enters the cells through
      the mannose 6-phosphate receptor pathway. Over two dozen PPT mutations have been
      found in PPT-deficient patients worldwide. In the United States, all PPT
      deficient patients show "GROD" histology but the age of onset of symptoms is
      later in some children due to the presence of missense mutations that result in
      enzymes with residual PPT activity. Now that INCL is known to be caused by a
      defect in a soluble lysosomal enzyme, appropriate therapies may be forthcoming.
      Prospects for therapy include enzyme replacement, stem cell transplantation, gene
      therapy, and metabolic therapy aimed at depleting the abnormal substrate
      accumulation in the disease.

PMID- 11332778
TI  - Biochemistry of neuronal ceroid lipofuscinoses.
AB  - This chapter summarizes the recent advances that have been made with respect to
      biochemical characterization of the neurodegenerative diseases collectively known
      as neuronal ceroid lipofuscinoses (NCL) or Batten disease. Genomic and proteomic
      approaches have presently identified eight different forms of NCL (namely, CLN1
      through CLN8) based on mutations in specific genes. CLN1 and CLN2 are caused by
      mutations in genes that encodes lysosomal enzymes,palmitoyl protein thioesterase
      and pepstatin-insensitive proteinase, respectively. The protein involved in the
      etiology of CLN3 is a highly hydrophobic, presumably transmembrane protein. NCL
      are considered as lysosomal storage diseases because of the accumulation of
      autofluorescent inclusion bodies. The composition of inclusion bodies varies in
      different forms of the NCL. The major storage component in CLN2 is the subunit c
      of mitochondrial ATP synthase complex and its accumulation is the direct result
      of lack of CLN2p in this disease. Mannose-6-phosphorylated glycoproteins
      accumulate in CLN3 and most likely their accumulation is the result of an
      intrinsic activity of the CLN3 protein. Significant levels of oligosaccharyl
      diphosphodolichol also accumulate in CLN3 and CLN2, whereas lysosomal
      sphingolipid activator proteins (saposins A and D) constitute major component of
      the storage material in CLN 1. The issue of selective loss of neuronal and
      retinal cells in NCL still remains to be addressed. Identification of natural
      substrates for the various enzymes involved in NCL may help in the
      characterization of the cytotoxic factor(s) and also in designing rationale
      therapeutic interventions for these group of devastating diseases.

PMID- 11332779
TI  - Discordant and nondiscordant twins: comparative multimethod risk assessment in
      the neonatal period.
AB  - Full-term neonate twins from weight-discordant pairs were compared with
      nondiscordant pairs on perinatal variables, minor physical anomalies,
      developmental status, and temperament/interactive measures. For perinatal
      variables, twins from the top quartile of discordance were found to be at higher
      risk than other twins. Both the total group of discordant twins and twins with
      the most extreme discordance had higher weighted minor physical anomaly scores,
      more minor physical anomalies, and lower developmental status scores than
      nondiscordant twins. For temperament, twins in the extreme discordant group were
      more active while awake than twins in the nondiscordant group. The results are
      discussed in relation to expected group differences in perinatal measures, the
      timing during gestation of insults related to discordance and minor physical
      anomalies, and the significance of behavioral differences between cotwins versus
      between groups. Implications for developmental risk for both twins from
      discordant pairs are discussed.

PMID- 11332780
TI  - Alcohol use among Dominican and Puerto Rican adolescents residing in New York
      City: role of Hispanic group and gender.
AB  - Hispanic groups are often aggregated when examining adolescent drinking. The
      objective of this study was to determine the roles of Hispanic group (Puerto
      Rican versus Dominican) and gender in alcohol use among inner-city youth. Sixth
      and seventh graders in 22 New York City schools who identified themselves as
      Puerto Rican or Dominican completed self-report questionnaires at two assessments
      (N = 849 at baseline; N = 678 at 1-year follow-up). Dominican adolescents
      generally engaged in more alcohol use than Puerto Rican adolescents. In a number
      of cases, gender moderated the effect of Hispanic group on drinking.
      Specifically, Dominican boys reported greater use than Dominican girls, but use
      was similar across gender for Puerto Rican adolescents. These findings highlight
      the importance of considering Hispanic group and gender when examining adolescent
      drinking.

PMID- 11332781
TI  - Social facilitation of object-oriented hand use in a Rett syndrome variant girl:
      implications for partial preservation of an hypothesized specialized cerebral
      network.
AB  - Partial preservation of object-oriented hand use (OOHU) was studied behaviorally
      in a 6-1/2-year-old girl with the preserved speech variant (PSV) of Rett syndrome
      (RS), associated with a T 158 missense MeCP2 mutation and favorably skewed X
      inactivation. At home, OOHU was limited except for self-feeding. When examined,
      overall time invested in toy play was only 38% of that of healthy subjects, and
      also, by comparison with healthy subjects, less when autonomous than when
      socially-facilitated (13% vs 63%). Good interest in and responsiveness to people
      translated into better motivation for OOHU. She responded to others' requests for
      grasping and handling objects and used them to reinforce affiliations with
      people. Results were discussed in terms of a disruption of the formation of a
      specialized OOHU cerebral network in RS, partially compensated for by the
      favorably skewed X-inactivation, which among other effects permitted functional
      retention of the network segment incorporating social influence and motivation.

PMID- 11332782
TI  - Is this a behavior problem or normal temperament?

PMID- 11332783
TI  - Dietary recommendations to prevent and manage chronic pediatric health
      conditions: adherence, intervention, and future directions.
AB  - This review provides a summary of the dietary aspects of pediatric health
      conditions. Within each condition, dietary recommendations are reviewed, and
      adherence rates, factors affecting adherence, and known interventions are
      reported. Findings indicate that knowledge is necessary but not sufficient for
      dietary change. Interventions specifically targeting diet appear more promising
      than interventions aimed at global treatment adherence. Behavioral interventions
      and group treatment modalities also appear promising. Recommendations for future
      research include a systematic assessment of barriers to dietary adherence across
      populations, integration of the research on normative development of eating
      behavior in childhood, and the application of this information to the design and
      implementation of future treatment.

PMID- 11332784
TI  - Differential response of operant self-injury to pharmacologic versus behavioral
      treatment.
AB  - The purpose of this study was to investigate the hypothesis that self-injurious
      behavior (SIB) maintained by environmental factors will be more effectively
      treated by behavioral treatments than by haloperidol. Fifteen subjects were
      enrolled in this study. The efficacy of both haloperidol and a behavioral
      treatment was assessed. At the onset of treatment, subjects were randomized to
      receive either haloperidol or a placebo. During each day of treatment, data were
      collected during sessions with a behavioral treatment and sessions without a
      behavioral treatment. Behavioral treatment resulted in a statistically
      significant decrease in SIB, but haloperidol did not. Eighty-three percent of
      subjects were classified as responders to the behavioral treatment whereas only
      25% of the subjects were responders to haloperidol (p = .019). We conclude that
      individuals with operant SIB are more likely to respond to behavioral treatments
      than to haloperidol.

PMID- 11332785
TI  - "Motor" impairment in Asperger syndrome: evidence for a deficit in
      proprioception.
AB  - Motor impairment has frequently been described in Asperger syndrome (AS), a
      pervasive developmental disorder included in the Diagnostic and Statistical
      Manual of Mental Disorders, 4th Edition (DSM-IV). Previous research focusing on
      this motor dysfunction has yielded inconsistent results, and the "clumsiness"
      observed clinically remains poorly defined. To clarify further the issue of motor
      impairment, we compared a group of 10 children and young adults who met DSM-IV
      criteria for AS with a control group with no neurological impairment. Subjects
      were matched on age, sex, socioeconomic status, and Verbal IQ. A broad battery of
      motoric tests was administered. Subjects with AS were found to perform more
      poorly than controls on tests of apraxia, one-leg balance with eyes closed,
      tandem gait, and repetitive finger-thumb apposition. No significant differences
      were found on tests of finger tapping, grooved pegboard, trail making, or visual
      motor integration. The pattern of impairments suggests that a proprioceptive
      deficit may underlie the incoordination observed in AS and that these individuals
      may be overreliant on visual input to maintain balance and position in space.

PMID- 11332786
TI  - Beyond infant colic.
AB  - Some of the most interesting cases in pediatric practice evolve through time.
      What may begin as a clear, well defined problem with a predictable natural
      history and an accepted intervention strategy may develop into a more complex,
      multi-faceted set of problems. It is these children who potentially provide
      clinicians with new insights into behaviors. This case of a colicky infant
      illustrates the wide spectrum of behavioral and physiological symptoms that
      emerge from a specific underlying behavioral phenomenon. It also emphasizes the
      significant benefit derived from a longitudinal perspective of developmental
      events.

PMID- 11332787
TI  - A two-year-old boy with language regression and unusual social interactions.

PMID- 11332788
TI  - Extraordinary changes in behavior in an infant after a brief separation.

PMID- 11332789
TI  - A school-aged child with delayed reading skills.

PMID- 11332790
TI  - School underachievement in the fifth grade.

PMID- 11332791
TI  - Selective mutism.

PMID- 11332792
TI  - "By the way,...her foot is turned out.".

PMID- 11332793
TI  - Recurrent abdominal pain.

PMID- 11332794
TI  - Cyclic vomiting.

PMID- 11332795
TI  - Recurrent episodes of asthma in a 10 year old.

PMID- 11332796
TI  - Diurnal and nocturnal enuresis in a 6 year old.

PMID- 11332797
TI  - Twelve-year-old girl with chronic fatigue, school absence, and fluctuating
      somatic symptoms.

PMID- 11332798
TI  - Persistent cough in an adolescent.

PMID- 11332799
TI  - Authority of the brain.

PMID- 11332800
TI  - "What can I do to enhance the development of a premature infant with chronic lung
      disease?".

PMID- 11332801
TI  - Maria: stubborn, willful, and always full of energy.

PMID- 11332802
TI  - The discovery of marijuana use by a parent of an early adolescent.

PMID- 11332803
TI  - An adolescent who abruptly stops his medication for attention-deficit
      hyperactivity disorder.

PMID- 11332804
TI  - Decision making about medical care in an adolescent with a life-threatening
      illness.

PMID- 11332805
TI  - Temper tantrums, impulsivity, and aggression in a preschool-aged boy.

PMID- 11332806
TI  - School refusal and emotional lability in a 6-year-old boy.

PMID- 11332807
TI  - Recent onset of sleepwalking in early adolescence.

PMID- 11332808
TI  - Erica: a question of sexual abuse.

PMID- 11332809
TI  - Sammy: gender identity concerns in a 6-year-old boy.

PMID- 11332810
TI  - The use of family drawings by children in pediatric practice.

PMID- 11332811
TI  - "We've tried everything and nothing works": family-centered pediatrics and
      clinical problem-solving.

PMID- 11332812
TI  - ADHD, divorce, and parental disagreement about the diagnosis and treatment.

PMID- 11332813
TI  - Cosleeping (bedsharing) among infants and toddlers.

PMID- 11332814
TI  - Responding to parental concerns after a prenatal diagnosis of trisomy 21.

PMID- 11332815
TI  - Parental request to withhold a hearing test in a newborn of deaf parents.

PMID- 11332816
TI  - Feeding problems, sleep disturbances, and negative behaviors in a toddler.

PMID- 11332817
TI  - Parental refusal to immunize a 2-month-old infant.

PMID- 11332818
TI  - Early delay in motor development.

PMID- 11332819
TI  - Expressive language delay in a toddler.

PMID- 11332820
TI  - Large-scale management of insect resistance to transgenic cotton in Arizona: can
      transgenic insecticidal crops be sustained?
AB  - A major challenge for agriculture is management of insect resistance to toxins
      from Bacillus thuringiensis (Bt) produced by transgenic crops. Here we describe
      how a large-scale program is being developed in Arizona for management of
      resistance to Bt cotton in the pink bollworm, Pectinophora gossypiella (Saunders)
      (Lepidoptera: Gelechiidae), and other insect pests of cotton. Financial support
      from growers makes this program possible. Collaboration between the Arizona
      Cotton Research and Protection Council, the University of Arizona, and government
      agencies has led to development of resistance management guidelines, a remedial
      action plan, and tools for monitoring compliance with the proposed guidelines.
      Direct participation in development of resistance management policies is a strong
      incentive for growers to invest in resistance management research. However, more
      research, regularly updated regulations, and increased collaboration between
      stakeholders are urgently needed to maintain efficacy of Bt toxins in transgenic
      crops.

PMID- 11332821
TI  - Varroa destructor infestation in untreated honey bee (Hymenoptera: Apidae)
      colonies selected for hygienic behavior.
AB  - Honey bee (Apis mellifera L.) colonies bred for hygienic behavior were tested in
      a large field trial to determine if they were able to resist the parasitic mite
      Varroa destructor better than unselected colonies of"Starline" stock. Colonies
      bred for hygienic behavior are able to detect, uncap, and remove experimentally
      infested brood from the nest, although the extent to which the behavior actually
      reduces the overall mite-load in untreated, naturally infested colonies needed
      further verification. The results indicate that hygienic colonies with queens
      mated naturally to unselected drones had significantly fewer mites on adult bees
      and within worker brood cells than Starline colonies for up to 1 yr without
      treatment in a commercial, migratory beekeeping operation. Hygienic colonies
      actively defended themselves against the mites when mite levels were relatively
      low. At high mite infestations (>15% of worker brood and of adult bees), the
      majority of hygienic colonies required treatment to prevent collapse. Overall,
      the hygienic colonies had similar adult populations and brood areas, produced as
      much honey, and had less brood disease than the Starline colonies. Thus, honey
      bees bred for hygienic behavior performed as well if not better than other
      commercial lines of bees and maintained lower mite loads for up to one year
      without treatment.

PMID- 11332822
TI  - Resistance to Acarapis woodi by honey bees (Hymenoptera: Apidae): divergent
      selection and evaluation of selection progress.
AB  - Two generations of honey bees, Apis mellifera L., selected for resistance to
      tracheal mites, Acarapis woodi (Rennie), were produced from a foundation stock.
      The mite resistant lines had significantly low mite abundances and prevalences in
      each selected generation. The high mite-resistant lines of the first selected
      generation showed resistance equal to that of bees that had undergone natural
      selection from tracheal mite infestations for 3 yr in New York. Additionally, the
      high mite-resistant lines of the second selected generation and Buckfast bees had
      significantly lower mite abundances and prevalences than honey bees from control
      colonies which had never been exposed to tracheal mite infestation in Ontario.
      These results corroborate studies that have shown that honey bees possess genetic
      components for tracheal mite resistance that can be readily enhanced in a
      breeding program. The two methods used for evaluating relative resistance of
      honey bees to tracheal mites, a short-term bioassay and evaluation in field
      colonies, were positively correlated (rs = 0.64, P < 0.001).

PMID- 11332823
TI  - Relative effectiveness of selected stilbene optical brighteners as enhancers of
      the beet armyworm (Lepidoptera: Noctuidae) nuclear polyhedrosis virus.
AB  - The addition of a stilbene optical brightener, Tinopal LPW, at 1% concentration
      (wt:wt) significantly reduced the LC50 of the beet armyworm nuclear polyhedrosis
      virus (SeMNPV) from 2.9 PIB/mm2 to 0.02 PIB/mm2. Moreover, the LT50 of SeMNPV was
      reduced by 34% by the addition of Tinopal LPW. Seven other structurally related
      stilbene brighteners were also tested as viral enhancers. Five of these
      brighteners (Tinopal LPW, Blankophor BBH, Blankophor HRS, Blankophor P167, and
      Blankophor RKH) reduced LD50, whereas three brighteners (Blankophor BSU,
      Blankophor DML, and Blankophor LPG) had little effect. Among the active
      brighteners, LC50s were reduced by 10.5-fold (Blankophor P167), 52.4-fold
      (Blankophor RKH), 87.3-fold Tinopal LPW), 131-fold (Blankophor BBH), and >400
      fold (Blankophor HRS). LT50s were also decreased by the addition of Blankophor
      BBH, Blankophor P167, and Blankophor RKH, but were increased by the addition of
      Blankophor BSU, Blankophor DMLO, and Blankophor LPG to SeMNPV suspensions.

PMID- 11332824
TI  - Evaluation of synergistic interactions between the Colorado potato beetle
      (Coleoptera: Chrysomelidae) pathogen Beauveria bassiana and the insecticides,
      imidacloprid, and cyromazine.
AB  - Laboratory studies investigated the interaction between the fungal entomopathogen
      Beauveria bassiana (Balsamo) Vuillemin and sublethal doses of the insecticides
      imidacloprid and cyromazine when applied to larvae of the Colorado potato beetle,
      Leptinotarsa decemlineata (Say). When second instars were fed potato leaf discs
      treated with sublethal doses of imidacloprid and a range of doses of B. bassiana,
      a synergistic action was demonstrated. Similar results were observed when larvae
      were sprayed directly with B. bassiana conidia and immediately fed leaf discs
      treated with imidacloprid. No synergistic interaction was detected when larvae
      were fed leaf discs treated with sublethal doses ofimidacloprid 24 h after
      application of B. bassiana conidia to larvae. However, a synergistic interaction
      was detected when larvae were fed leaf discs treated with imidacloprid and
      sprayed with B. bassiana conidia 24 h later. Although sublethal doses of both
      imidacloprid and the triazine insect growth regulator (IGR) cyromazine prolonged
      the duration of the second instar, only imidacloprid interacted with B. bassiana
      to produce a synergistic response in larval mortality. In leaf consumption
      studies, the highest dose of B. bassiana tested promoted feeding in inoculated
      second instars. Feeding was inhibited when larvae were fed foliage treated with
      sublethal doses of imidacloprid and significantly reduced when fed foliage
      treated with a sublethal dose of cyromazine. Starvation of larvae for 24 h
      immediately after B. bassiana treatment produced a similar result to the combined
      treatment of B. bassiana and imidacloprid and increased the level of mycosis when
      compared with B. bassiana controls. Imidacloprid treatment affected neither the
      rate of germination of B. bassiana conidia on the insect cuticle nor the rate at
      which conidia were removed from the integument after application. The statistical
      analysis used to detect synergism and the possible role of starvation-induced
      stress factors underlying the observed synergistic interactions are discussed.

PMID- 11332825
TI  - Antagonism between Beauveria bassiana and imidacloprid when combined for Bemisia
      argentifolii (Homoptera: Aleyrodidae) control.
AB  - Imidacloprid and the entomopathogenic fungus Beauveria bassiana (Balsamo)
      Vuillemin are both used to control the whitefly Bemisia argentifolii Bellows &
      Perring. We tested whether the two control strategies acted additively,
      synergistically, or antagonistically when combined for whitefly control. We found
      antagonism in that B. bassiana inhibited the effectiveness of imidacloprid. When
      B. bassiana was combined with imidacloprid, insect response was either less than
      or similar to (depending on B. bassiana rates) that when imidacloprid was used
      alone. Adding imidacloprid to B. bassiana treatments always increased mortality,
      but the increase was less than additive. Beauveria bassiana spore germination and
      colony formation were not inhibited by imidacloprid in vitro, and B. bassiana did
      not adsorb or degrade imidacloprid in a tank mix. We hypothesize that B. bassiana
      caused a behavioral response that reduced insect feeding and uptake of
      imidacloprid.

PMID- 11332826
TI  - Effects of Serratia marcescens on the F1 generation of laboratory-reared
      Heliothis virescens (Lepidoptera: Noctuidae).
AB  - The effects of the bacterium Serratia marcescens (Bizio) was investigated on the
      F1 generation of laboratory-reared Heliothis virescens (F.). There was no
      difference in adult male or female longevity (i.e., parental generation) for
      individuals inoculated with S. marcescens as larvae (Serratia treatment) and
      those that were free of the bacterium (control treatment). However, the number of
      eggs laid and the prevalence of eclosion of eggs from Serratia treatment adults
      were reduced relative to control treatment adults. A very low number of F1
      Serratia treatment eggs exhibited signs of infection, but a higher prevalence of
      mortality was observed for F1 larvae (n = 2,888) for the Serratia (3.5-4.6%) than
      for the control (1.1-1.5%) treatment. No S. marcescens was isolated from dead
      control larvae; whereas, 48 -54% of dead F1 larvae for the Serratia treatment
      were positive for the bacterium. However, there was no significant difference in
      larval weights between treatments. There were also no differences in either
      mortality or weight of F1 male pupae between treatments, but F1 female pupae were
      significantly smaller and prevalence of mortality was higher for the Serratia
      treatment. Serratia marcescens was not isolated from any of the control F1 pupae,
      but 6% of pupal cadavers for the Serratia treatment were positive for the
      bacterium. No S. marcescens was recovered from the meconia of any of the F1
      adults (n = 2,600) regardless of treatment, and there were no differences in
      adult weights between treatments. Although sublethal effects of S. marcescens
      were detected, the impact and prevalence of the bacterium were tremendously
      reduced over the F1 generation in the absence of all but the most basic
      management strategies.

PMID- 11332828
TI  - Potential for outbreaks of leafrollers (Lepidoptera: Tortricidae) in California
      apple orchards using mating disruption for codling moth suppression.
AB  - Two species of leafrollers, Argyrotaenia citrana (Fernald) and Pandemis pyrusana
      Kearfott, represent serious obstacles to the implementation of mating disruption
      for control of codling moth in coastal California apple orchards. Larval and
      adult densities of A. citrana and P. pyrusana and subsequent fruit damage were
      compared under different codling moth control treatments. Leafroller larval
      counts and levels of fruit damage were significantly higher in most plots that
      were untreated or treated only with codling moth pheromone. Leafroller fruit
      damage levels in these plots were commonly between 10 and 15% at harvest. As
      summer larval counts were good predictors of fruit damage levels, larval sampling
      could be a useful tool for predicting leafroller outbreaks. Use of pheromone
      trapping for A. citrana to detect localized outbreaks within an orchard was not
      useful and failed to correlate with larval numbers, whereas adult monitoring for
      P. pyrusana appears more promising. Efforts to implement a codling moth mating
      disruption program in California must include changes in strategies for
      monitoring and controlling leafroller species.

PMID- 11332827
TI  - Desiccant dusts synergize the effect of Beauveria bassiana (Hyphomycetes:
      Moniliales) on stored-grain beetles.
AB  - Diatomaceous earth (DE) is a desiccant insecticide and most efficacious in low
      humidity. It acts on insect cuticle by absorbing lipids, and perhaps by cuticular
      abrasion. Beauveria bassiana (Balsamo) Vuillemin, an entomopathogenic fungus, is
      most efficacious in high humidity and has a complex interaction with cuticular
      lipids. Interaction between these materials may enhance insect control
      performance. Assays with stored-grain beetles were conducted with B. bassiana at
      rates of 11, 33, 100, and 300 mg of conidia per kilogram of grain with and
      without single rates of DE that killed 10% or less of the target beetles. The
      assays revealed synergism in effects on adult Rhyzopertha dominica (F.) and
      Oryzaephilus surinamensis (L.) at all doses. There was statistically significant
      synergism for adult Cryptolestes ferrugineus (Stephens) and larval R. dominica
      but at only one B. bassiana rate for each target. Both amorphous silicon dioxide,
      a sorptive dust, and diamond dust, an abrasive, showed synergistic interaction
      with B. bassiana on adult R. dominica. These results may provide a basis for a
      least-toxic approach to control of stored-product beetles and for efficacy
      enhancing formulation of entomopathogenic fungi.

PMID- 11332829
TI  - Host plant-induced changes in detoxification enzymes and susceptibility to
      pesticides in the twospotted spider mite (Acari: Tetranychidae).
AB  - Adult female twospotted spider mites, Tetranychus urticae Koch, reared on lima
      bean plants were moved to cucumber, maize, or new lima bean plants (the latter
      being a control) and evaluated after 24 h or 7 d for changes in susceptibility to
      three pesticides and in levels of related detoxification enzymes. The largest and
      most consistent changes were observed in mites feeding on cucumber.
      Susceptibility of mites on cucumber to the synthetic pyrethroids bifenthrin and
      lambda-cyhalothrin was greater than that of mites reared on lima bean and maize
      after only 24 h on the plants, and remained higher after 7 d. Mites on cucumber
      also were more susceptible to the organophosphate dimethoate than were mites on
      lima bean, but only after 7 d on the host. Susceptibility was inversely related
      to activities of both general esterase and glutathione S-transferase (GST) in
      mites on cucumber; general esterase and GST activities were 60 and 25% lower,
      respectively, than activities of twospotted spider mite on lima bean after 7 d of
      feeding. Mites on maize were slightly but significantly more susceptible than
      those on lima bean to bifenthrin, but not to lambda-cyhalothrin, after 7 d and to
      dimethoate after 24 h but not after 7 d. General esterase and GST activities in
      twospotted spider mite fed on maize for 24 h were 20 and 16% higher,
      respectively, than activities in twospotted spider mite on lima bean, but general
      esterase activity was 30% lower than lima bean-fed mites and GST was not
      different after 7 d. Thus, plant-induced changes in general esterase activity,
      perhaps in combination with GST activity, in twospotted spider mite appear to be
      inversely related to, and possibly responsible for, changes in susceptibility of
      twospotted spider mite to several pesticides, particularly the synthetic
      pyrethroids. General esterases appear to play less of a role in the
      detoxification of the organophosphate insecticide dimethoate.

PMID- 11332830
TI  - Response of cotton to prebloom square loss.
AB  - In 1996 and 1997, various intensities of prebloom square removal were applied to
      three cultivars of cotton grown in Mississippi. With the exception of one
      cultivar in 1997, all cultivars were B. thuringiensis (Bt)-transgenic cotton. At
      harvest, the number of bolls and seed cotton weight was recorded for all plants
      in each square removal treatment. All cultivars responded similarly to square
      loss. A yield increase (overcompensation) was observed in the treatment where all
      squares were removed from the plant one week after squaring began. Only the
      treatment where all squares were removed before bloom significantly reduced yield
      and caused a large (>7 d) delay in crop maturation. Otherwise, moderate levels of
      square removal (approximately 20-50% of prebloom squares) had little impact on
      overall lint production. However, the patterns of cotton production on the plants
      were significantly influenced by the square removal treatments. The removal of
      relatively more or larger squares increased seed cotton production in late-season
      fruiting cohorts and on 'vegetative' branches. Compensation for square loss
      occurred by increasing the relative number and weight of bolls produced
      subsequent to early-season square removal. Typically, early-season square loss
      increased the value of later-season fruiting cohorts, especially the midseason
      cohorts and bolls on vegetative branches. The implications of prebloom square
      loss, including the compensatory ability of the cotton plant, on insect
      management are discussed.

PMID- 11332831
TI  - Establishment of Cry9C susceptibility baselines for European corn borer and
      southwestern corn borer (Lepidoptera: Crambidae).
AB  - In 1997 and 1998, Cry9C susceptibility baselines were established for field
      collected populations of European corn borer, Osrinia nubilalis (Hubner), and
      southwestern corn borer, Diatraea grandiosella Dyar. Bioassay of neonate European
      corn borer larvae of 16 colonies collected from the midwestern United States
      indicated LC50 values ranging from 13.2 to 65.1 ng of Cry9C protein per square
      centimeter. Neonate European corn borer LC50 values ranged from 46.5 to 214
      ng/cm2. Neonate larvae of three colonies of southwestern corn borer collected
      from the southern and southwestern United States exhibited LC50 values from 16.9
      to 39.9 ng of Cry9C protein per square centimeter. Southwestern corn borer
      neonate LC90 confidence limit values ranged from 40.3 to 157 ng of Cry9C protein
      per centimeter. The most sensitive southwestern corn borer colony was collected
      from the Mississippi delta exhibiting an LC50 value of 22.6 ng of Cry9C per cm2
      and also displayed the widest LC0 confidence limits of 40.3-94.8 ng of Cry9C per
      cm2. Geographic baseline susceptibility data establishes the natural genetic
      variation and provides the foundation for future testing of insect populations
      exposed to increased use of Bacillus thuringiensis-based crops. Insect resistance
      management and stewardship of Cry9C will rely upon baseline data for the
      validation of discriminating dose assays for European corn borer and southwestern
      corn borer.

PMID- 11332832
TI  - Treatment thresholds for stink bugs (Hemiptera: Pentatomidae) in cotton.
AB  - The green stink bug, Acrosternum hilare (Say), the southern green stink bug,
      Nezara viridula (L), and the brown stink bug, Euschistus servus (Say), were
      predominant phytophagous Pentatomidae detected during 1995-1997 in cotton in
      South Carolina. These species occurred in similar numbers in conventional and
      transgenic cotton 'NuCOTN33B', containing the gene for expression of CryIA(c)
      delta-endotoxin of Bacillus thuringiensis Berliner variety kurstaki. Adult stink
      bugs moved into cotton from wild and cultivated alternate hosts during July, and
      reproducing populations usually were detected in cotton from late July into
      September. Applications of either methyl parathion (0.56 kg [AI]/ha) directed for
      stink bugs or lambda-cyhalothrin (0.037 kg [AI]/ha) or cyfluthrin (0.056 kg
      [AI]/ha) for control of cotton bollworm, Helicoverpa zea (Boddie), provided
      effective control of pentatomids in NuCOTN33B or conventional 'DP5415' and
      increased yields compared with untreated plots. Fiber quality did not differ
      among treated or untreated plots of NuCOTN33B. The ground-cloth technique was
      used to estimate populations of stink bugs, and data indicated that treatment at
      one bug per 2 m of row adequately protected cotton from yield loss due to stink
      bug damage. Observations on boll damage indicated that treatment might be
      necessary if >20-25% reveal internal symptoms of feeding injury during mid- to
      late season. More detailed damage thresholds should be developed to complement an
      approach based on population monitoring. This study validated current
      recommendations for management of pentatomids in cotton, demonstrated the
      necessity of threshold use for stink bugs in transgenic cultivars expressing
      endotoxin from B. thuringiensis, and provided insight into further development of
      management options for pentatomids in the crop.

PMID- 11332833
TI  - Seasonal abundance of aphids (Homoptera: Aphididae) in wheat and their role as
      barley yellow dwarf virus vectors in the South Carolina coastal plain.
AB  - Aphid (Homoptera: Aphididae) seasonal flight activity and abundance in wheat,
      Triticum aestivum L., and the significance of aphid species as vectors of barley
      yellow dwarf virus were studied over a nine-year period in the South Carolina
      coastal plain. Four aphid species colonized wheat in a consistent seasonal
      pattern. Greenbug, Schizaphis graminum (Rondani), and rice root aphid,
      Rhopalosiphum rufiabdominalis (Sasaki), colonized seedlingwheat immediately after
      crop emergence, with apterous colonies usually peaking in December or January and
      then declining for the remainder of the season. These two aphid species are
      unlikely to cause economic loss on wheat in South Carolina, thus crop managers
      should not have to sample for the subterranean R. rufiabdominalis colonies. Bird
      cherry-oat aphid, Rhopalosiphum padi (L.), was the second most abundant species
      and the most economically important. Rhopalosiphum padi colonies usually remained
      below 10/row-meter until peaking in February or March. Barley yellow dwarf
      incidence and wheat yield loss were significantly correlated with R. padi peak
      abundance and aphid-day accumulation on the crop. Based on transmission assays,
      R. padi was primarily responsible for vectoring the predominant virus serotype
      (PAV) we found in wheat. Pest management efforts should focus on sampling for and
      suppressing this aphid species. December planting reduced aphid-day accumulation
      and barley yellow dwarf incidence, but delayed planting is not a practical
      management option. English grain aphid, Sitobion avenae (F.), was the last
      species to colonize wheat each season, and the most abundant. Sitobion avenae was
      responsible for late-season virus transmission and caused direct yield loss by
      feeding on heads and flag leaves during an outbreak year.

PMID- 11332834
TI  - Tomicus piniperda (Coleoptera: Scolytidae) shoot-feeding characteristics and
      overwintering behavior in Scotch pine Christmas trees.
AB  - Overwintering behavior of Tomicus piniperda (L.) was studied in a Scotch pine
      (Pinus sylvestris L.) Christmas tree plantation in Indiana (1992-1994) and a
      plantation in Michigan (1994). In general, adults feed inside shoots during
      summer, then move to overwintering sites at the base of trees in autumn. In early
      autumn, adults were most often found in shoot-feeding tunnels that were still
      surrounded by green needles, whereas few were in tunnels surrounded by yellow or
      brown needles. For all years and sites combined, the range in the percentage of
      recently tunneled shoots that contained live T. piniperda adults decreased from
      89 to 96% in mid-October, to 15- 66% in early November, to 2-10% in mid-November,
      and to 0-2% by late November to early December. In each year, the first
      subfreezing temperatures in autumn occurred in October, before most adults left
      the shoots. Of 1,285 T. piniperda-tunneled shoots, one to seven tunnels (mean =
      1.6) and zero to three adults were found per infested shoot. Of these 1,285
      attacked shoots, 55% of the shoots had one tunnel, 33% had two, 9% had three, 3%
      had four, and <1% had five to seven tunnels each. When two or more tunnels
      occurred in a single shoot, adults were most commonly found in the innermost
      (most basal) tunnel. For the 2,070 tunnels found in the 1,285 shoots, average
      shoot thickness at the tunnel entrance was 6.0 mm, average distance from the
      tunnel entrance to the shoot tip was 6.3 cm, and average tunnel length was 2.3
      cm. Four Scotch pine Christmas trees were dissected in January 1993. Eighty
      percent of the tunneled shoots were in the upper quarter of the tree crown and
      98% were in the upper half. For the four trees inspected in January, one live
      adult was found in a shoot and 85 adults were found in the outer bark along the
      lower trunk from 1 cm below the soil line to 19 cm above the soil line. No
      overwintering adults were found outside the trunk in the duff or soil near the
      base of each test tree. Implications of these results are discussed in terms of
      surveying, timing the cutting of Christmas trees, and cutting height for
      Christmas trees.

PMID- 11332835
TI  - Modified atmosphere treatments as a potential disinfestation technique for
      arthropod pests in greenhouses.
AB  - Incidental transport of arthropods on plant material can be a significant mode of
      pest entry into greenhouses. We evaluated the use of controlled atmosphere
      treatments as a potential way to eliminate arthropod pests on plant propagules
      (i.e., cuttings or small rooted plants). Lethal exposures to CO2 or N2 were
      determined for common greenhouse pests including fungus gnat larvae, Bradysia
      sp.; green peach aphid, Myzus persicae (Sulzer); sweetpotato whitefly, Bemisia
      sp.; twospotted spider mite, Tetranychus urticae Koch; and western flower thrips,
      Frankliniella occidentalis (Pergande). We also studied the effect of pest
      species, life stage, and presence or absence of plants on efficacy of modified
      atmosphere treatments. Finally, effects of modified atmospheres on plant quality
      were evaluated for several bedding plant species including begonia, Begonia
      semperflorens-cultorum Hort. 'Cocktail Series', chrysanthemum, Dendranthema
      grandiflora Tzvelev., geranium, Pelargonium X hortorum L.H. Bailey, and
      impatiens, Impatiens wallerana Hook f., and among cultivars of geranium and
      chrysanthemum. Exposure for 12-18 h to >99% N2 or CO2 caused complete mortality
      of aphids, mites, thrips, and whiteflies. Fungus gnat larvae were more tolerant
      of hypoxic conditions. Adult mites and eggs were equally susceptible. For most
      pests, there was no difference in response to atmospheres modified by CO2 or N2.
      However, there was variation in response among plant species and cultivars, with
      effects ranging from delayed flowering to mortality. Despite the possibility of
      adverse effects on some plants, this work indicates that use of modified
      atmospheres has potential to eliminate arthropod pests on plant propagules before
      they are introduced into greenhouses.

PMID- 11332837
TI  - Preference of temperate Chinese elms (Ulmus spp.) for the adult Japanese beetle
      (Coleoptera: Scarabaeidae).
AB  - Trees of newly acquired Ulmus species originating from the temperate regions of
      China and growing at The Morton Arboretum, Lisle, IL, were evaluated in no-choice
      and multiple-choice laboratory bioassays and cage-studies for feeding preference
      for adults of the Japanese beetle, Popillia japonica Newman. Ulmus lanceaefolia,
      U. prunifolia, U. pseudopropinqua, and U. taihangshanensis were less preferred
      for feeding by adult Japanese beetles. No-choice, multiple-choice, and cage
      feeding studies revealed that Ulmus wallichiana was moderately preferred, and U.
      procera and U. americana were highly preferred for feeding. Dry fecal pellet
      weights were strongly correlated with the percent of leaf tissue removed. Feeding
      preference in the multiple-choice study was strongly correlated with feeding
      preference in the cage study and in the no-choice study. Likewise, adult feeding
      preference in the cage study was strongly correlated with preference in the
      multiple-choice and no-choice studies. The less preferred species of U.
      lanceafolia, U. prunifolia, U. pseudopropinqua, and U. taihangshanensis show
      promise for future elm breeding programs.

PMID- 11332836
TI  - Economic thresholds for Aphis gossypii (Hemiptera: Aphididae) on Citrus
      clementina.
AB  - Different levels of Aphis gossypii Glover were maintained on clementine trees by
      means of isolation inside mesh cages. Clementine yield loss was correlated with
      the number of aphids per square meter of canopy, obtaining the corresponding
      formula. Starting from this formula, the economic injury level (EIL) was
      calculated as follows: [218,333C + 11,130.6 VP0K]/[57.08 VP0K - 100C] = EIL
      (aphids/m2), where C = total insecticide cost per hectare, V = fruit price per
      kilogram, P0 = yield per hectare of a minimum pest level orchard, and K =
      reduction of injury due to treatment. Starting from the EIL, the economic
      threshold, the environmental EIL, and the environmental economic threshold were
      obtained. Formulae relating the number of aphids per square meter with other
      simpler indices expressing these thresholds (percentage of infested shoots,
      infested shoots per 0.25 m2 ring, index of infestation, percentage of occupied
      rings, and number of weekly captured aphids in a yellow trap) also were
      calculated.

PMID- 11332838
TI  - Effects of neem seed derivatives on behavioral and physiological responses of the
      Cosmopolites sordidus (Coleoptera: Curculionidae).
AB  - Both in a choice and multi-choice laboratory tests, fewer adults of the banana
      root borer, Cosmopolites sordidus (Germar), settled under the corms of the
      susceptible banana "Nakyetengu" treated with 5% aqueous extract of neem seed
      powder or cake or 2.5 and 5% emulsified neem oil than on water-treated corms.
      Feeding damage by larvae on banana pseudostem discs treated with 5% extract of
      powdered neem seed, kernel, or cake, or 5% emulsified neem oil was significantly
      less than on untreated discs. The larvae took much longer to locate feeding
      sites, initiate feeding and bore into pseudostem discs treated with extract of
      powdered neem seed or kernel. Few larvae survived when confined for 14 d on neem
      treated banana pseudostems; the survivors weighed two to four times less than the
      larvae developing on untreated pseudostems. Females deposited up to 75% fewer
      eggs on neem-treated corms. In addition, egg hatching was reduced on neem-treated
      corms. The higher the concentration of neem materials the more severe the effect.

PMID- 11332839
TI  - Effect of trap position, habitat, and height on the capture of pepper maggot
      flies (Diptera: Tephritidae).
AB  - Trapping results indicate that pepper maggot, Zonosemata electa (Say), flies
      occupy tree canopies adjacent to fields when not on host plants. Several in- and
      near-field trap positions were used to find a reliable monitoring system for
      adult pepper maggots. Traps baited with liquid ammonium hydroxide (Stills-style
      trap), hung in the canopy of trees on the edges of pepper fields, caught
      significantly more Z. electa flies than when positioned lower along the treeline
      or in the field. In a second experiment, significantly more pepper maggot flies
      were captured in sugar maples compared with choke cherry trees, which indicates a
      pest preference for certain nonhost habitats. The lowest trap height tested (2.1
      m) failed to capture Z. electa flies in either tree species when the pest
      population level was low. These studies demonstrated that pepper maggot flies can
      be reliably detected with Stills-style traps positioned at approximately 6.4 m
      height within the canopy of sugar maple trees adjacent to pepper fields. Fruit
      oviposition scars also are useful site-specific indicators of pepper maggot
      presence/absence and may aid in determining if insecticide applications are
      necessary and in timing sprays.

PMID- 11332840
TI  - Bumble bee (Hymenoptera: Apidae) activity and pollination levels in commercial
      tomato greenhouses.
AB  - Commercial greenhouse studies were conducted to assess levels of pollination of
      tomato (Lycopersicon esculentum Mill.) flowers in relation to bumble bee (Bombus
      impatiens Cresson) colony activity and colony densities. For the assessment of
      pollination levels of tomato flowers, five categories were defined based on
      bruising levels caused by bumble bee pollination. Colony activity was measured as
      bee trips per ha/d using electric powered photodiode monitors inserted into the
      hive entrance. Levels of pollination were positively correlated with bee activity
      levels, up to a mean of approximately 400 pollen grains per stigma per day, after
      which greater activity did not result in further increases in daily pollination
      levels. Densities of colonies in the commercial greenhouses studied ranged from
      7.6 to 19.8 colonies per hectare with a mean of 11.6 +/- 0.9. We found that an
      average activity of 2,000 bee trips per hectare per day was more than adequate to
      ensure sufficient pollination, and that this level of activity could be achieved
      with 7-15 colonies per hectare, depending on greenhouse conditions. Greenhouses
      requiring >15 colonies per hectare to achieve this level of pollination may be
      able to increase bee activity through alteration of greenhouse conditions. Across
      50-m rows of tomato plants, levels of pollination decreased with increasing
      distance from bee colonies, suggesting that colonies should be evenly distributed
      throughout the greenhouses.

PMID- 11332841
TI  - Effects of field applied residues and length of exposure to tebufenozide on the
      obliquebanded leafroller (Lepidoptera: Tortricidae).
AB  - Studies were conducted with the obliquebanded leafroller, Choristoneura rosaceana
      (Harris), and tebufenozide to determine the influence of various factors on the
      efficacy of this insecticide under field conditions. Larvae were exposed to apple
      foliage collected from commercial orchards at different intervals after
      insecticide applications. Mortality of neonates on actively growing (terminal)
      and mature (spur) foliage 10 d after an airblast sprayer application of
      tebufenozide was 0 and 35-74%, respectively. Feeding by larvae was also assessed
      on collected foliage. There was significantly less feeding on tebufenozide
      treated foliage than chlorpyrifos- and nontreated foliage (P < 0.05). In the
      second study, to determine the efficacy of tebufenozide in the absence of larval
      movement to terminals with sublethal residues, terminal foliage with
      obliquebanded leafroller larvae was collected from two commercial orchards 24 h
      after an airblast sprayer application of tebufenozide. After larvae were confined
      on this terminal foliage in the laboratory for 10 d, mortality was >90%. In the
      third study, to examine the effects of obliquebanded leafroller movement to
      foliage with sublethal residues, we designed a laboratory bioassay in which
      larvae were exposed to foliage treated with tebufenozide and transferred to
      untreated foliage after various exposure intervals. The higher the concentration
      of tebufenozide, the less exposure time was necessary to cause high levels of
      mortality of neonates. The terminal feeding behavior ofobliquebanded leafroller
      larvae, low residues on terminal foliage before the end of the typical 2-wk spray
      interval, and the length of exposure necessary for high levels of mortality may
      decrease the effectiveness of tebufenozide for obliquebanded leafroller control.

PMID- 11332842
TI  - Integrated control of oriental fruit moth (Lepidoptera: Tortricidae) in peach
      orchards using insecticide and mating disruption.
AB  - The efficacy of an integrated and a conventional oriental fruit moth, Grapholita
      molesta (Busck), control program was compared using 4-ha blocks of peach at three
      Niagara Peninsula farms during 1997-1999. In the integrated program, chlorpyrifos
      was used to control first-generation larvae and mating disruption using Isomate
      M100 pheromone dispensers was used to control the second and third generations.
      In the conventional program, chlorpyrifos was used to control first-generation
      larvae and pyrethroids were used to control larvae of the later generations. The
      average release rate of pheromone was 23.7-26.4 mg/ha/h over a period of 86-91 d.
      The pheromone treatment reduced the capture of moths in pheromone-baited traps on
      average by 98%, suggesting a high level of disruption. The integrated program
      provided control of oriental fruit moth similar to the control provided by a
      conventional program. The mean percentage of peach shoots infested with first-
      and second-generation larvae, and fruit infested with third-generation larvae was
      not significantly greater in the integrated-program blocks during the 3-yr study.
      The elimination of insecticide sprays from the integrated-program blocks did not
      result in an increase in damage caused by plant bugs. The incidence of damage
      caused by other pests was negligible in both the integrated and conventional
      blocks.

PMID- 11332843
TI  - Penetration of the eastern subterranean termite into soil treated at various
      thicknesses and concentrations of Dursban TC and Premise 75.
AB  - The ability of eastern subterranean termites, Reticulitermes flavipes (Kollar),
      to penetrate various concentrations and treatment thicknesses ranging from 1.0 to
      50.0 mm of Dursban TC and Premise 75 was evaluated in a laboratory bioassay.
      Termites penetrated only a few millimeters into 500 ppm Dursban TC-treated soil
      at all thicknesses. As concentration decreased, termite penetration into Dursban
      TC-treated soil increased with termites generally penetrating completely through
      5.0- and 0.5-ppm treatments. Termites penetrated at least 30% into 10-, 25-, and
      50-mm thicknesses of 100 ppm Premise 75. Termites generally completely penetrated
      all concentrations < or = 100 ppm and thicknesses < or = 5 mm. At 7 d, termite
      mortality was 100% at all treatment thicknesses of Dursban TC at 500 and 50 ppm.
      At 5.0 and 0.5 ppm Dursban TC, termite mortality ranged from approximately 45 to
      98% across all treatment thicknesses. At 100- and 10-ppm concentrations of
      Premise 75-treated soil, termites suffered > or = 75% mortality. Premise 75 at
      1.0 and 0.1 ppm generally killed < or = 50% of the assayed termites at all
      treatment thicknesses.

PMID- 11332844
TI  - Effects of sublethal exposure to imidacloprid on subsequent behavior of
      subterranean termite Reticulitermes virginicus (Isoptera: Rhinotermitidae).
AB  - Experiments were conducted to determine whether subterranean termites,
      Reticuliternes virginicus (Banks), previously exposed to sublethal doses of
      imidacloprid (Premise), and allowed to recover for 1 wk, demonstrated behavioral
      aversion to a subsequent exposure. Worker termites experiencing a previous
      sublethal but debilitating exposure to imidacloprid-treated sand (either 10 or
      100 ppm for 4 h) showed no apparent aversion to a second encounter with
      imidacloprid-treated sand under conditions of this experiment. If these
      laboratory results hold in the field and termites traveling through a zone of
      soil treated with imidacloprid are impaired but subsequently recover, they will
      be just as likely as their naive nestmates to reenter the treated area if their
      travels take them through the nonrepellent application a second time. Our results
      also indicate that a sublethal exposure to imidacloprid can affect termite
      tunneling behavior. Many worker termites that received an initial 4-h exposure to
      100 ppm imidacloprid-treated sand died, but those that survived tunneled
      significantly less than did their naive nestmates, as did some termites exposed
      to 10 ppm imidacloprid.

PMID- 11332845
TI  - Decapitation impacting effect of topically applied chlorpyrifos on
      acetylcholinesterase and general esterases in susceptible and resistant German
      cockroaches (Dictyoptera: Blattellidae).
AB  - The effect of topically applied chlorpyrifos on acetylcholinesterase and other
      esterases in heads and decapitated bodies of CSMA and Crawford German cockroaches
      was examined with spectrophotometric enzyme assay and native polyacrylamide gel
      electrophoresis. The toxicity of chlorpyrifos was greatly reduced in decapitated
      CSMA male cockroaches with LD50 value 17.1-fold higher than that of normal CSMA
      cockroaches. Acetylcholinesterase activity from heads was significantly higher in
      the Crawford compared with the CSMA strain and did not change until 24 h after
      chlorpyrifos in vivo treatment in both strains. The p-nitrophenyl butyrate (NPB)
      esterase activities from both heads and decapitated bodies of the resistant
      Crawford strain were significantly greater than the susceptible CSMA strain. The
      p-NPB esterase activity was significantly inhibited by chlorpyrifos in vivo
      treatment, and total p-NPB esterase activity was significantly reduced in
      decapitated bodies compared with heads of both strains. Native polyacrylamide gel
      electrophoresis (PAGE) analysis of extracts solubilized with Triton X-100 from
      heads and decapitated bodies revealed five major esterase bands and an
      acetylcholinesterase (AChE) band with a high capability of hydrolyzing alpha
      naphthyl butyrate and acetylthiocholine, respectively. In the heads of
      susceptible CSMA male cockroaches, the activity of mobile isozymes d1 and d2 was
      completely inhibited at 24 h after chlorpyrifos application, and isozyme e was
      partially inhibited. In contrast, isozymes c1 and c2 from the decapitated bodies
      of CSMA cockroaches were mostly affected at 24 h after the topical application of
      chlorpyrifos. The activities of acetylcholinesterase and esterase isozymes a and
      b from the decapitated body remained uninhibited in both strains. Inhibition of
      isozymes d1 and d2 seems to be more important in chlorpyrifos intoxication than
      acetylcholinesterase.

PMID- 11332846
TI  - Bait matrix for delivery of chitin synthesis inhibitors to the formosan
      subterranean termite (Isoptera: Rhinotermitidae).
AB  - The efficacy of three chitin synthesis inhibitors, diflubenzuron, hexaflumuron,
      and chlorfluazuron, incorporated into a novel bait matrix to kill the Formosan
      subterranean termite, Coptotermes formosanus Shiraki, was evaluated in the
      laboratory. The bait matrix was significantly preferred by C. formosanus over
      southern yellow pine wood in a two-choice feeding test. Bait formulations
      containing 250 ppm of the three chitin synthesis inhibitors were presented to
      termite nests with 2,500 individuals (80% workers and 20% soldiers) in the
      presence of alternative food sources consisting of cardboard and southern yellow
      pine, Pinus taeda L., wood. None of the bait formulations were significantly
      repellent or feeding deterrent to the termite workers evidenced by the lack of
      full consumption of alternative food sources. All nests presented with the bait
      formulations died within 9 wk, whereas the control nests (bait with no chitin
      synthesis inhibitors) remained alive 6 mo after the end of the study. No
      significant differences in consumption were observed among the chitin synthesis
      inhibitor treatments. Importance of this study for the improvement of current
      bait technology is discussed.

PMID- 11332847
TI  - Acceptance and intake of gel and liquid sucrose compositions by the Argentine ant
      (Hymenoptera: Formicidae).
AB  - Liquids and gels are common delivery forms used in commercial ant baits, but the
      relative effectiveness of each is unknown. We compared the feeding responses of
      the Argentine ant, Linepithema humile (Mayr), to liquid and gel compositions of
      sucrose. In choice assays, more workers were counted on gel than liquid; however,
      substantially more liquid was consumed. Because workers could stand on the gel,
      more workers could feed simultaneously on the gel. The feeding bouts of
      individual workers, however, were much less efficient at extracting sucrose in
      gel form. Workers fed eightfold longer on the gel, yet removed fivefold less
      sucrose than workers feeding on liquid. This potential bias should be considered
      during attraction and palatability studies that use physically different bait
      compositions. When the toxicant fipronil was added to the compositions, a greater
      proportion of the colony died after workers had fed on liquid than gel baits.
      This finding suggests that liquid formulations may provide more effective control
      of Argentine ants due to the greater speed and abundance in which it is ingested.

PMID- 11332848
TI  - Nutritional ecology of the formosan subterranean termite (Isoptera:
      Rhinotermitidae): feeding response to commercial wood species.
AB  - The feeding preferences of the Formosan subterranean termite, Coptotermes
      formosanus Shiraki, were tested in three separate experiments on 28 different
      wood species. Experiment 1 was a multiple-choice test designed to test relative
      preferences among 24 wood species commercially available in New Orleans, LA.
      Experiment 2 was a similar study designed to test relative preferences among 21
      wood species shown or reported to be unpalatable to the Formosan subterranean
      termite. Experiment 3 was a no-choice test to examine the feeding deterrence of
      the 10 least preferred wood species. Preference was determined by consumption
      rates. Birch (Betula alleghaniensis Britton), red gum (Liquidambar styraciflua
      L.), Parana pine [Araucaria angustifolia (Bert.) 1, sugar maple (Acer saccharum
      Marsh.), pecan (Carya illinoensis Wangenh.), and northern red oak (Quercus rubra
      L.) were the most preferred species by C. formosanus in order of consumption
      rate. All of these species were significantly more preferred than southern yellow
      pine (Pinus taeda L.), widely used for monitoring. Sinker cypress [ = old growth
      bald cypress, Taxodium distichum (L.)], western red cedar (Thuja plicata Donn),
      Alaskan yellow cedar (Chamaecyparis nootkatensis D. Don), eastern red cedar
      (Juniperus virginiana L.), sassafras [Sassafras albidum (Nutt.)], Spanish cedar
      (Cedrella odorata L.), Honduras mahogany (Swietenia macrophyla King), Indian
      rosewood (Dalbergia latifolia Roxb.), Honduras rosewood (D. stevensonii Standl.),
      and morado (Machaerium sp.) induced significant feeding deterrence and mortality
      to C. formosanus. The last eight species produced 100% mortality after 3 mo.

PMID- 11332849
TI  - An insensitive acetylcholinesterase confers resistance to methomyl in the beet
      armyworm Spodoptera exigua (Lepidoptera: Noctuidae).
AB  - Two forms of acetylcholinesterase were identified in field populations of the
      beet armyworm, Spodoptera exigua (Hubner), collected from cotton in San Joaquin
      Valley, CA. Strains (BESS and BKRR) homogeneous for each variant were isolated
      and their relative susceptibilities to methomyl, chlorpyrifos, and chlorpyrifos
      oxon assessed by topical application bioassay. In comparisons with a laboratory
      susceptible strain (DOW), BKRR and BESS expressed 68-fold and sevenfold
      resistance, respectively, to the carbamate methomyl. Neither strain was cross
      resistant to chlorpyrifos or its oxygen analog (chlorpyrifos-oxon). In
      biochemical studies, the BKRR AChE enzyme was approximately 30-fold and sixfold
      more insensitive to methomyl and chlorpyrifos-oxon, respectively, compared with
      the DOW enzyme. The correlation between the toxicological and biochemical studies
      provides strong evidence that target-site insensitivity is an important mechanism
      of resistance to methomyl. The lack of significant cross-resistance to
      chlorpyrifos suggests that the insensitive AChE in these field populations was
      selected by methomyl alone and not by the organophosphate.

PMID- 11332850
TI  - Modeling the dynamics of adaptation to transgenic corn by western corn rootworm
      (Coleoptera: Chrysomelidae).
AB  - A simulation model of the population dynamics and genetics of the western corn
      rootworm, Diabrotica virgifera virgifera LeConte, was created for a landscape of
      corn, soybean, and other crops. Although the model was created to study a 2-locus
      problem for beetles having genes for resistance to both crop rotation and
      transgenic corn, during this first phase of the project, the model was simulated
      to evaluate only resistance management plans for transgenic corn. Allele
      expression in the rootworm and toxin dose in the corn plant were the two most
      important factors affecting resistance development. A dominant resistance allele
      allowed quick evolution of resistance to transgenic corn, whereas a recessive
      allele delayed resistance >99 yr. With high dosages of toxin and additive
      expression, the time required to reach 3% resistance allele frequency ranged from
      13 to >99 yr. With additive expression, lower dosages permitted the resistant
      allele frequency to reach 3% in 2-9 yr with refuges occupying 5-30% of the land.
      The results were sensitive to delays in emergence by susceptible adults and
      configuration of the refuge (row strips versus blocks).

PMID- 11332851
TI  - Variation in susceptibility of Diadegma insulare (Hymenoptera: Ichneumonidae) to
      permethrin.
AB  - Six field populations of the parasitoid Diadegma insulare (Cresson) were
      collected from Mexico and the United States and tested for their susceptibility
      to permethrin by using a glass-vial residue bioassay. Significant differences
      existed in susceptibility, with one population significantly more susceptible
      than the other five. Susceptibility of D. insulare increased when they were
      reared for several generations in the greenhouse in the absence of selection. D.
      insulare was less suceptible to permethrin than the adult stage of its host,
      Plutella xylostella (L.), from a laboratory colony, but more susceptible than
      those hosts collected from a commercial field. Our data suggest that a field
      population of D. insulare appeared to increase its tolerance to permethrin much
      more slowly than P. xylostella.

PMID- 11332852
TI  - Distribution and abundance of insecticide resistant greenbugs (Homoptera:
      Aphididae) and validation of a bioassay to assess resistance.
AB  - Laboratory bioassays were conducted to determine the toxicity of four
      insecticides (ethyl parathion, chlorpyrifos, malathion, and carbofuran) to
      insecticide-susceptible and resistant populations of greenbug, Schizaphis
      graminum (Rondani). These bioassays were used to develop and validate a
      discriminating concentration for assessing insecticide resistance in greenbug
      populations in the field. Samples from wheat and sorghum in two states, Oklahoma
      and Kansas, indicated that insecticide resistance persists in greenbug
      populations over a large area at a low level.

PMID- 11332853
TI  - Fitness consequences of malathion-specific resistance in red flour beetle
      (Coleoptera: Tenebrionidae) and selection for resistance in the absence of
      malathion.
AB  - Malathion resistance in the red flour beetle, Tribolium castaneum (Herbst), is a
      worldwide problem and is very stable once it becomes widespread in natural
      populations. In the absence of insecticide the proportion of resistant phenotypes
      may rapidly decline but the development of resistance does not always involve
      reduced fitness. Malathion-specific resistance in T. castaneum seems not to
      involve any loss of fitness in laboratory or field conditions. Susceptible
      beetles were in competition with resistant beetles at different initial
      frequencies and modifications of susceptible gene frequency were estimated in
      these laboratory populations over 10 generations. A significant decrease in
      susceptible gene frequency was observed in Tribolium populations over time. The
      selection coefficient of the susceptible allele was estimated and the fitness of
      susceptible alleles in all tests was observed to range from 0.89 to 0.93 compared
      with the fitness of resistant genotypes, which was assumed to be 1. Data provided
      evidence that the resistant strains exhibited fitness advantages in the absence
      of malathion. We also compared the biotic potential (fecundity and developmental
      time) of the susceptible strain, the homozygous malathion-specific resistant
      strain, and their hybrids. Malathion-specific resistant strains showed an 8 -23%
      increase in biotic potential relative to the susceptible strain. These findings
      are consistent with those of malathion-specific resistance in T. castaneum; the
      fitness of the insects seems independent of the genetic background and the
      fitness of the resistant insects is not affected by this resistance mechanism.

PMID- 11332854
TI  - Categories of resistance to greenbug (Homoptera: Aphididae) biotype I in Aegilops
      tauschii germplasm.
AB  - Categories of resistance to greenbug, Schizaphisgraminum (Rondani), biotype I,
      were determined in goatgrass, Aegilops tauschii (Coss.) Schmal., accession 1675
      (resistant donor parent), 'Wichita' wheat, Triticum aestivum L., (susceptible
      parent), and an Ae. tauschii-derived resistant line, '97-85-3'. Antibiosis was
      assessed using the intrinsic rate of increase (rm) of greenbugs confined to each
      of the three genotypes. Neither parent nor the resistant progeny expressed
      antibiosis. Mean rm values for greenbug I on Wichita (0.0956), and Ae. tauschii
      (0.10543) were not significantly different. Mean rm values for Wichita and 97-85
      3 were also not significantly different. Antixenosis was determined by allowing
      aphids a choice to feed on plants of each of the three genotypes. Ae. tauschii
      1675 exhibited antixenosis, but this resistance was not inherited and expressed
      in '97-85-3'. In experiments comparing Wichita and Ae. tauschii 1675, greenbug I
      population distributions were not significantly different on Wichita at 24 h, but
      were shifted toward Wichita at 48 h. In the second antixenosis experiment, there
      were no significant differences in greenbug I population distributions on 97-85-3
      or Wichita at 24 or 48 h. When all three lines were compared, there were no
      significant differences in greenbug biotype I populations at 24 or 48 h after
      infestation. Comparisons of proportional dry plant weight loss (DWT) and SPAD
      meter readings were used to determine tolerance to greenbug I feeding. Ae.
      tauschii 1675 and 97-85-3 were highly tolerant compared with Wichita. Infested
      and uninfested Ae. tauschii 1675 DWT was nonsignificant, and infested Wichita
      plants weighed significantly less than uninfested plants. When Wichita and 97-85
      3 were contrasted, DWT of infested and uninfested Wichita plants were
      significantly different, but those of 97-85-3 were not. Mean percent leaf
      chlorophyll losses for the three genotypes, as measured by the SPAD chlorophyll
      meter, were as follows: Wichita = 65%; Ae. tauschii 1675 = 25%; and 97-85-3 =
      39%. Percent leaf chlorophyll losses caused by greenbug feeding was significantly
      different in comparisons between Wichita and Ae. tauschii 1675, and comparisons
      between Wichita and 97-85-3, although feeding damage was not significantly
      different in comparisons between Ae. tauschii 1675 and 97-85-3. These data
      provided further evidence of the expression of tolerance to greenbug feeding in
      Ae. tauschii 1675 and 97-85-3.

PMID- 11332856
TI  - Genotypic variability and mode of action of Colorado potato beetle (Coleoptera:
      Chrysomelidae) resistance in seven Solanum species.
AB  - Accessions from seven wild Solanum species were evaluated in the field for
      resistance to the Colorado potato beetle, Leptinotarsa decemlineata (Say). The
      multivariate insect population density data were analyzed using factor analysis.
      The factors extracted corresponded to relevant phases of the insect's life cycle
      and provided information on the mode of resistance (antixenosis and antibiosis)
      of the plant species. S. berthaultii, S. capsicibaccatum, S. jamesii, S.
      pinnatisectum, and S. trifidum demonstrated both antixenosis and antibiosis but
      expressed different levels of resistance. The mode of resistance of S.
      polyadenium seemed to be antibiosis and that of S. tarijense antixenosis. Genetic
      variability and heritability of insect resistance traits within accessions was
      trivial or inconsistent for all Solanum species studied.

PMID- 11332857
TI  - Sequential sampling plans for western flower thrips (Thysanoptera: Thripidae) on
      greenhouse cucumbers.
AB  - The development of cost-effective and reliable sampling programs for the
      management of western flower thrips, Frankliniella occidentalis (Pergande), on
      greenhouse cucumbers is important for getting growers to adopt economic injury
      levels and economic thresholds. The objectives of this study were to develop two
      sequential sampling plans. A fixed-precision sequential sampling plan was
      designed for estimating F. occidentalis adult density at a fixed-precision level
      on cucumber flowers. Also, a sequential sampling plan for classifying thrips
      population levels as below or above economic thresholds was developed to assist
      in decision making for the timing of pesticide applications. Both sequential
      sampling plans were validated using a resampling simulation technique on nine
      independent data sets ranging in density from 1.25 to 12.95 adults per flower.
      With the fixed-precision sampling plan, average means obtained in 100 repeated
      simulation runs were within the 95% CI of the estimated mean for all data sets.
      Appropriate levels of precision for the different population densities were
      recommended based on the simulation results. With sequential sampling for
      classifying the population levels of thrips in terms of an economic threshold, it
      has the advantage of requiring smaller sample sizes to determine the population
      status when the population densities differ greatly from the critical density
      (i.e., economic threshold). However, this plan needs a great number of samples
      when population density is close to the critical density. In this case, use of a
      combination of both sampling plans is recommended.

PMID- 11332855
TI  - Restriction fragment length polymorphism markers associated with silk maysin,
      antibiosis to corn earworm (Lepidoptera: Noctuidae) larvae, in a dent and sweet
      corn cross.
AB  - Maysin, a C-glycosylflavone in maize silk, has insecticidal activity against corn
      earworm, Helicoverpa zea (Boddie), larvae. Sweet corn, Zea mays L., is a
      vulnerable crop to ear-feeding insects and requires pesticide protection from ear
      damage. This study was conducted to identify maize chromosome regions associated
      with silk maysin concentration and eventually to transfer and develop high silk
      maysin sweet corn lines with marker-assisted selection (MAS). Using an F2
      population derived from SC102 (high maysin dent corn) and B31857 (low maysin sh2
      sweet corn), we detected two major quantitative trait loci (QTL). It was
      estimated that 25.6% of the silk maysin variance was associated with segregation
      in the genomic region of npi286 (flanking to p1) on chromosome 1S. We also
      demonstrated that a1 on chromosome 3L had major contribution to silk maysin
      (accounted for 15.7% of the variance). Locus a1 has a recessive gene action for
      high maysin with the presence of functional p1 allele. Markers umc66a (near c2)
      and umc105a on chromosome 9S also were detected in this analysis with minor
      contribution. A multiple-locus model, which included npi286, a1, csu3 (Bin 1.05),
      umc245 (Bin 7.05), agrr21 (Bin 8.09), umc105a, and the epistatic interactions
      npi286 x a1, a1 x agrr21, csu3 x umc245, and umc105a x umc245, accounted for
      76.3% of the total silk maysin variance. Tester crosses showed that at the a1
      locus, SC102 has functional A1 alleles and B31857 has homozygous recessive a1
      alleles. Individuals of (SC102 x B31857) x B31857 were examined with MAS and
      plants with p1 allele from SC102 and homozygous a1 alleles from B31857 had
      consistent high silk maysin. Marker-assisted selection seems to be a suitable
      method to transfer silk maysin to sweet corn lines to reduce pesticide
      application.

PMID- 11332858
TI  - Life history attributes of Indian meal moth (Lepidoptera: Pyralidae) and
      Angoumois grain moth (Lepidoptera: Gelechiidae) reared on transgenic corn
      kernels.
AB  - The Indian meal moth, Plodia interpunctella (Hubner), and Angoumois grain moth,
      Sitotroga cerealella (Olivier), are two globally distributed stored-grain pests.
      Laboratory experiments were conducted to examine the impact that corn (Zea mays
      L.) kernels (i.e., grain) of some Bacillus thuringiensis Berliner (Bt) corn
      hybrids containing CrylAb Bt delta-endotoxin have on life history attributes of
      Indian meal moth and Angoumois grain moth. Stored grain is at risk to damage from
      Indian meal moth and Angoumois grain moth; therefore, Bt corn may provide a means
      of protecting this commodity from damage. Thus, the objective of this research
      was to quantify the effects of transgenic corn seed containing CrylAb delta
      endotoxin on Indian meal moth and Angoumois grain moth survival, fecundity, and
      duration of development. Experiments with Bt grain, non-Bt isolines, and non-Bt
      grain were conducted in environmental chambers at 27 +/- 1 degrees C and > or =
      60% RH in continuous dark. Fifty eggs were placed in ventilated pint jars
      containing 170 g of cracked or whole corn for the Indian meal moth and Angoumois
      grain moth, respectively. Emergence and fecundity were observed for 5 wk.
      Emergence and fecundity of Indian meal moth and emergence of Angoumois grain moth
      were significantly lower for individuals reared on P33V08 and N6800Bt, MON 810
      and Bt-11 transformed hybrids, respectively, than on their non-Bt transformed
      isolines. Longer developmental times were observed for Indian meal moth reared on
      P33V08 and N6800Bt than their non-Bt-transformed isolines. These results indicate
      that MON 810 and Bt-11 CrylAb delta-endotoxin-containing kernels reduce
      laboratory populations of Indian meal moth and Angoumois grain moth. Thus,
      storing Bt-transformed grain is a management tactic that warrants bin scale
      testing and may effectively reduce Indian meal moth and Angoumois grain moth
      populations in grain without application of synthetic chemicals or pesticides.

PMID- 11332859
TI  - Parasitism rates of Muscidifurax raptorellus and Nasonia vitripennis
      (Hymenoptera: Pteromalidae) after individual and paired releases in New York
      poultry facilities.
AB  - Commercially reared parasitoids were released into three high-rise, caged-layer
      poultry houses; one house received only N. vitripennis Walker, the second house
      received only M. raptorellus Kogan & Legner, and the third house received an
      equal ratio of both species. Overall, house fly parasitism by M. raptorellus was
      never higher than 7% in any house. Most parasitism in the M. raptorellus release
      house was attributed to N. vitripennis. Parasitism of house fly pupae by M.
      raptorellus did not significantly increase during or after the 6-wk release
      period in the house that received both parasitoids. However, a depression in
      total parasitism was not detected when releases of the two species were made in
      this house.

PMID- 11332860
TI  - Cyclic vomiting syndrome: age-old syndrome and new insights.
AB  - Cyclic vomiting is a variant of migraine that is discussed in depth. The
      importance of the diagnostic criteria, differential diagnosis, supportive and
      pharmacologic therapies is stressed.

PMID- 11332861
TI  - Headaches in children and adolescents: update 2001.
AB  - It is now recognized that headaches are frequent in children and even more common
      in adolescents. In this article, the recent significant changes that have taken
      place in the classification, epidemiology, evaluation, and treatment of headaches
      in children and adolescents are reviewed.

PMID- 11332862
TI  - Triptans in childhood and adolescence.
AB  - The triptans are medications that are the most important advance, to date, in the
      treatment of migraine. Their use in adolescents is highlighted, including
      indications, dosages, benefits, and adverse effects.

PMID- 11332863
TI  - Status migrainosus in children and adolescents.
AB  - Data concerning status migrainosus in children and adolescents is sparse. The
      varied clinical presentations, diagnostic evaluation, and treatment modalities
      are discussed.

PMID- 11332864
TI  - Chronic nonprogressive headaches in children and adolescents.
AB  - Chronic nonprogressive headaches (CNPHA) are common in children and increase in
      frequency in adolescents. Features are usually, but not always, distinct from
      those of migraine. CNPHA have also been called chronic daily headaches, tension
      type headaches, muscle contraction headaches, and psychogenic headaches. These
      headaches represent a diagnostic and therapeutic challenge to family physicians,
      pediatricians, and pediatric neurologists. The evaluation is time-consuming and
      the treatment frustrating and often unsuccessful. They are a significant cause of
      school absences. This review addresses the epidemiology classification,
      pathogenesis, clinical characteristics, evaluation, and treatment of this
      disorder.

PMID- 11332865
TI  - Indomethacin-responsive headaches in children and adolescents.
AB  - Headache is a common symptom in childhood and adolescence. Effective therapy for
      this symptom is based on the specific headache syndrome. This article presents
      examples of the four recognized Indomethacin-responsive headache syndromes
      encountered in pediatrics including exertional headache, cyclic-cluster migraine,
      chronic paroxysmal hemicrania, and hemicrania continua. Although uncommon
      conditions, successful treatment depends on recognition of these indomethacin
      responsive headache syndromes.

PMID- 11332866
TI  - Headache in the pediatric emergency department.
AB  - Headache is one of the most common presenting complaints to emergency
      departments. Although the overwhelming majority of these headaches are benign and
      self-limited, headache can be the initial symptom of life-threatening disorders.
      It is therefore essential for physicians to have a rational approach to the
      evaluation of a child or adolescent who presents to the emergency department with
      headache. The purpose of this article is to review the causes, evaluation, and
      appropriate investigations for nontraumatic headache in the pediatric emergency
      department.

PMID- 11332867
TI  - Complicated migraine and migraine variants.
AB  - Complicated migraine and migraine variants are relatively uncommon forms of
      migraine. This article reviews migraines, with special emphasis on diagnosis,
      differential diagnoses, and treatment.

PMID- 11332868
TI  - Opinion paper: statistics is not "bloodless" algebra.

PMID- 11332869
TI  - Alpha-dihydroergocryptine and predictive factors in migraine prophylaxis.
AB  - OBJECTIVE: A double-blind, crossover study was carried out to compare the
      efficacy of alpha-dihydroergocryptine mesylate (10 mg twice daily) vs propranolol
      (40 mg twice daily) in the prophylaxis of migraine without aura, and to identify
      possible predictors of therapeutic response by evaluating the symptomatological
      profile of individual migraine attacks and the autonomic cardiovascular response
      to noradrenergic and dopaminergic (cold pressor, bromocriptine) tests. PATIENTS
      AND METHODS: Forty migraineurs (10 males, 30 females) were randomized according
      to a two-period (3-month), two-treatment, crossover design. Efficacy was assessed
      using quantitative data recorded in the patient's headache diary. Data were
      evaluated using the Wallenstein's method. RESULTS: Both drugs showed a
      significant reduction in all the efficacy variables (headache attacks, days with
      headache, analgesic consumption) with no difference between treatments. Neither a
      bromocriptine test, nor a cold pressor test nor the symptomatological profile of
      individual migraine attacks differed between the two groups of migraine patients.
      Ten patients experienced at least one adverse drug reaction during the first
      period of the crossover design, 5 being treated with alpha-dihydroergocryptine
      and 5 with propranolol. CONCLUSIONS: It is concluded that alpha
      dihydroergocryptine is an effective medication for migraine prophylaxis. The
      biochemical tests and the type of psychological profile cannot be used to predict
      drug response.

PMID- 11332870
TI  - Restitution of alpha-topography by piracetam in post-stroke aphasia.
AB  - OBJECTIVE: Electroencephalographic and clinical effects of piracetam in post
      stroke aphasia were evaluated in a prospective, randomized, double-blind, placebo
      controlled trial. METHODS: In 24 patients with mild to moderate aphasia after
      ischemic stroke, quantitative topographic EEG at rest was studied before and
      after a 6-week treatment period. RESULTS: In the active treatment group, a
      significant shift in the alpha-rhythm from frontal to occipital regions was
      observed which may be due to a restitution of corticothalamic circuits involved
      in the generation of alpha-activity. CONCLUSION: Neuropsychological scores
      improved significantly and markedly in various domains of speech during piracetam
      treatment, whereas improvements were less marked and restricted to a few
      categories in the placebo group.

PMID- 11332871
TI  - Albumin-dependent digoxin transfer in isolated perfused human placenta.
AB  - OBJECTIVE: To determine the effects of albumin (BSA) concentration in perfusion
      medium on digoxin transfer in isolated perfused human placental cotyledon. STUDY
      DESIGN: Isolated placental cotyledons from 13 normal human placentas were dually
      perfused after cannulating artery and vein of the chorionic plate and piercing 4
      catheters through the corresponding basal plate with M199 medium enriched with
      BSA and glucose. Flow rates were 12 and 6 ml/min in the maternal and fetal
      circuits, respectively. Digoxin was added to the maternal reservoir at a final
      concentration of 5.51 +/- 1.00 ng/ml. BSA in maternal and fetal perfusate was
      kept at 3 concentrations: 1, 3 and 5 mg/ml (Groups I, II, III). Transplacental
      passage of digoxin was calculated from repeated fetal and maternal perfusate
      samples collected over 3 hours in the 3 groups. Digoxin levels were measured by
      FPIA (TDx, Abbott). RESULTS: There was no transfer of digoxin from the maternal
      to fetal compartment when the concentration of BSA was 1 mg/ml. Increasing the
      concentration of BSA led to a substantial increase in the transfer of digoxin to
      the fetal compartment. Steady state levels of digoxin in the fetal compartment
      were 0.61 +/- 0.19 ng/ml at 3 mg/ml of BSA. CONCLUSION: Maternal and fetal serum
      concentration of BSA affect digoxin transfer in isolated perfused human
      placentas. Three mg/ml are considered to be the optimal albumin concentration.

PMID- 11332872
TI  - Evaluation of some properties of individual bioequivalence (IBE) from replicate
      design studies.
AB  - BACKGROUND: One of the claimed benefits of the individual bioequivalence (IBE)
      approach has been that the aggregate regulatory model rewards a test formulation
      when it has a within-subject variation smaller than the reference product. Hauck
      et al. [1996] demonstrated that, in the absence of random variations, this
      property of IBE was due to the tradeoff between the difference of the means and
      the deviation between the intrasubject variances of the two formulations. The
      tradeoff was a consequence of the aggregate regulatory model. However,
      calculations of Endrenyi and Hao [1998] showed that, in the presence of random
      variations, not only rewards but also penalties can arise due to chance alone.
      METHODS: A data set of 55 investigations made public by the FDA in 1999 and
      containing replicate crossover designs was analyzed. Two parameters, AUC and
      Cmax, were determined in each investigation. RESULTS: The analyses of the FDA
      data indicate that: rewards and penalties occur at similar frequencies, large
      rewards and penalties are recorded quite often, and the aggregate IBE model is
      rather insensitive to the difference between the estimated means and is
      compatible with the frequent occurrence of large deviations. CONCLUSION: Rewards
      and penalties, apparently arising from random variations, can affect regulatory
      decisions on the acceptance of IBE and can lead to incorrect conclusions.

PMID- 11332873
TI  - Comparative bioavailability of 4 amoxicillin formulations in healthy human
      volunteers after a single dose administration.
AB  - OBJECTIVE: To compare the bioavailability of two amoxicillin oral suspension (250
      mg/5 ml) formulations and two amoxicillin capsule (500 mg) formulations
      (Amoxicilina from Medley S/A Industria Farmaceutica, Brazil, as test formulations
      and Amoxil from SmithKline Beecham Laboratorios Ltda., Brazil, as reference
      formulations) in 48 volunteers of both sexes. MATERIAL AND METHODS: The study was
      conducted open with a randomized two-period crossover design and a one-week
      washout period. Plasma samples were obtained over a 12-hour interval. Amoxicillin
      concentrations were analyzed by combined reversed phase liquid chromatography and
      tandem mass spectrometry (LC-MS-MS) with positive ion electrospray ionization
      using the selected ion monitoring method. From the amoxicillin plasma
      concentration vs. time curves the following pharmacokinetic parameters were
      obtained: AUC(last), AUC(0-infinity) and Cmax. RESULTS: Geometric mean of
      Amoxicilina/Amoxil 250 mg/5 ml individual percent ratio was 103.70% for
      AUC(last), 103.15% for AUC(0-infinity) and 106.79% for Cmax. The 90% confidence
      intervals were 97.82-109.94%, 97.40 to 109.24%, and 96.38-118.33%, respectively.
      Geometric mean of Amoxicilina/Amoxil 500 mg capsule individual percent ratio was
      93.26% for AUC(last), 93.27% for AUC(0-infinity) and 90.74% for Cmax. The 90%
      confidence intervals were 85.0-102.33%, 85.12-102.31%, and 80.14-102.73%,
      respectively. CONCLUSION: Since the 90% CI for both Cmax, AUC(last) and AUC(0
      inifnity) were within the 80-125% interval proposed by the Food and Drug
      Administration, it was concluded that Amoxicilina 250 mg/5 ml oral suspension and
      Amoxicilina 500 mg capsule were bioequivalent to Amoxil 250 mg/5 ml oral
      suspension and to Amoxil capsule 500 mg, respectively, with regard to both the
      rate and extent of absorption.

PMID- 11332874
TI  - Systemic bioavailability of nasally applied chlorphenamine maleate (0.4% nasal
      spray) relative to tablets administered perorally.
AB  - AIM: This study investigated the bioavailability of single doses of 1.12 and 2.24
      mg chlorphenamine maleate applied intranasally (0.4% nasal spray) relative to a
      single peroral dose of 8 mg chlorphenamine maleate (tablets). METHODS: Twenty
      four (24) subjects were treated with single nasal doses of 1.12 mg and 2.24 mg
      chlorphenamine maleate (0.4% nasal spray) and two 4 mg chlorphenamine maleate
      tablets (Piriton) on 3 separate study days according to a 3-way cross-over design
      with a 7-day wash-out between periods. Blood was sampled before and at 0.25,
      0.50, 1.0, 2.0, 3.0, 4.0, 6.0, 8.0, 12, 16 and 24 hours after drug
      administration. Additional blood samples were obtained 36, 48 and 72 hours after
      peroral administration only. All subjects were included in the pharmacokinetic
      analysis. RESULTS: Nasally applied chlorphenamine maleate was readily absorbed,
      reaching peak plasma levels after 0.25 to 3.0 hours. The dose-normalized
      estimated mean Cmax values were 1.24, 1.43 and 1.21 ng/ml for the peroral tablet
      and the 1.12 mg and 2.24 mg nasal dose, respectively. The dose-normalized
      estimated mean AUC(0-infinity) values were 25.91, 26.44 and 25.56 ng x h/ml for
      the tablet and the 1.12 and 2.24 mg nasal dose, respectively. The estimated
      treatment ratios (nasal dose to tablet) of the dose-normalized values for the
      1.12 mg nasal dose were 1.15 (900 CI: 1.0-1.32) and 1.02 (90% CI: 0.88-1.18) for
      Cmax and AUC(0-infinity), respectively, for the 2.24 mg nasal dose they were 0.98
      (90% CI: 0.85-1.13) and 0.99 (90% CI: 0.85-1.13) for Cmax and AUC(0-infinity),
      respectively. The other pharmacokinetic characteristics (tmax, t(1/2), lambda(z),
      AUC(0-tf), MRTtot, CL/f and Vz/f) were comparable across all treatments. These
      data indicate that the disposition of chlorphenamine maleate was independent of
      the route and dose of administration. CONCLUSIONS: Chlorphenamine maleate is
      readily absorbed after nasal application using a 0.4% nasal spray. The nasal
      administration showed that the systemic bioavailability at the two dose levels
      used was comparable to that for the tablet. Maximum concentrations on the low
      dose, however, were higher and those on the high dose were comparable to those
      for the tablet. The nasal application of chlorphenamine maleate does not alter
      the overall systemic exposure compared to the oral route.

PMID- 11332876
TI  - Magnetic resonance imaging (MRI) controlled outcome of side effects caused by
      ionizing radiation, treated with 780 nm-diode laser -- preliminary results.
AB  - BACKGROUND AND OBJECTIVE: Ionizing radiation therapy by way of various beams such
      as electron, photon and neutron is an established method in tumor treatment. The
      side effects caused by this treatment such as ulcer, painful mastitis and delay
      of wound healing are well known, too. Biomodulation by low level laser therapy
      (LLLT) has become popular as a therapeutic modality for the acceleration of wound
      healing and the treatment of inflammation. Evidence for this kind of application,
      however, is not fully understood yet. This study intends to demonstrate the
      response of biomodulative laser treatment on the side effects caused by ionizing
      radiation by means of magnetic resonance imaging (MRI). STUDY DESIGN/PATIENTS AND
      METHODS: Six female patients suffering from painful mastitis after breast
      ionizing irradiation and one man suffering from radiogenic ulcer were treated
      with lambda=780 nm diode laser irradiation at a fluence rate of 5 J/cm2. LLLT was
      performed for a period of 4-6 weeks (mean sessions: 25 per patient, range 19-35).
      The tissue response was determined by means of MRI after laser treatment in
      comparison to MRI prior to the beginning of the LLLT. RESULTS: All patients
      showed complete clinical remission. The time-dependent contrast enhancement curve
      obtained by the evaluation of MR images demonstrated a significant decrease of
      enhancement features typical for inflammation in the affected area. CONCLUSION:
      Biomodulation by LLLT seems to be a promising treatment modality for side effects
      induced by ionizing radiation.

PMID- 11332875
TI  - Bioequivalence of two rimantadine tablet formulations in healthy male volunteers
      after single dose administration.
AB  - AIM: The bioequivalence of two rimantadine tablet formulations was determined.
      METHODS: The study was designed as a randomized, two-period, two-sequence,
      crossover study. Twenty-four healthy male volunteers received a single 100 mg
      dose of rimantadine hydrochloride as test (Rimantadin Lachema 100 tbl. obd.,
      produced by Lachema, a.s., Brno, Czech Republic) and reference formulations
      (Elumadine 100 tbl. obd., produced by Forest Pharmaceuticals, St. Louis, USA).
      The two administrations were separated by 14 days and were performed in the
      fasting state. Blood samples were obtained at 15 time points during the interval
      0-120 h after administration. Rimantadine plasma concentrations were determined
      by gas chromatography with electron-capture detection. RESULTS: The geometric
      mean concentration-time profiles of rimantadine after administration of the two
      formulations were superimposable. The following pharmacokinetic parameters refer
      to the geometric mean [exp(mean +/- SD)] values for the test and reference
      formulations, respectively: Cmax (ng/ml) 70.5 (60.0-82.7) vs. 70.0 (59.9 to
      81.7), AUC(0-infinity) (ng x h/ml) 2872 (2224 to 3707) vs. 2849 (2195-3699),
      AUC(0-120 h) 2744 (2184-3448) vs. 2712 (2138-3441), t(1/2) (h) 25.8 (20.1-33.0)
      vs. 25.7 (20.6 to 32.1). Median (range) tmax (h) values were 4.5 (2.0-8.0) and
      6.0 (2.0-8.0). Parametric 90% confidence intervals for the expected mean
      percentage ratios (test/reference) of the pharmacokinetic variables were within
      the range of 97% to 105%. The median (91.1% confidence interval) difference in
      tmax was -0.3 h (-2.0-0.5). The point and interval estimates were identical when
      truncated AUCs (0-96 h, 0-72 h, 0-48 h and 0-24 h) were used in calculations.
      CONCLUSION: The two rimantadine formulations were equivalent in both the rate and
      extent ofbioavailability and they were also well tolerated. This study confirms
      the findings of other studies showing that for immediate release formulations of
      drugs with long half-lives shortening the duration over which blood samples are
      collected improves the economics, is more ethical and does not impair the quality
      of data.

PMID- 11332877
TI  - Spectral characterization of chlorophyll fluorescence in barley leaves during
      linear heating. Analysis of high-temperature fluorescence rise around 60 degrees
      C.
AB  - The spectral characteristics of chlorophyll fluorescence and absorption during
      linear heating of barley leaves within the range 25-75 degreesC (fluorescence
      temperature curve, FTC) were studied. Leaves with various content of light
      harvesting complexes (green, Chl b-less chlorina f2 and intermittent light grown)
      revealing different types of FTC were used. Differential absorption, emission and
      excitation spectra documented four characteristic phases of the FTC. The initial
      two FTC phases (a rise in the 46-49 degreesC region and a subsequent decrease to
      about 55 degreesC) mostly reflected changes in the fluorescence quantum yield
      peaking at about 685 nm. A steep second fluorescence rise at 55-61 degreesC was
      found to originate from a short-wavelength Chl a spectral form (emission maximum
      at 675 nm) causing a gradual blue shift of the emission spectra. In this
      temperature range, a clear correspondence of the blue shift in the emission and
      absorption spectra was found. We suggest that the second fluorescence rise in FTC
      reflects a weakening of the Chl a-protein interaction in the thylakoid membrane.

PMID- 11332878
TI  - NO-hemoglobin may be a light-sensitive source of nitric oxide both in solution
      and in red blood cells.
AB  - Hemoglobin in solution and inside red blood cells forms a complex with nitric
      oxide exhibiting a specific EPR signal both at room and liquid nitrogen
      temperatures. In the present paper it was shown that the nitrosyl complex of
      hemoglobin (NO-Hb) is photochemically sensitive and hence may serve as a source
      of free NO under He-Cd laser irradiation (441 nm). It was found that at laser
      light radiant power of 3.9 mW, room temperature and in the presence of oxygen,
      50% decrease of NO-Hb EPR signal occurred at doses of 54, 30, and 18 kJ/m2 for NO
      hemoglobin solution, hemolysed and intact erythrocytes, respectively. The
      detection of free NO produced as a result of NO-Hb photolysis was performed by
      means of a spin trap, nitronyl nitroxyl radical NNR, which in the presence of NO
      is transformed into imino nitroxyl radical (INR) showing different EPR signal. In
      isolated hemoglobin solution, 20 mM INR was accumulated under irradiation with
      the maximal dose of 700 kJ/m2. In intact cells the HbFe(2+)-NO photolysis and NO
      release occur with essentially higher efficacy. To produce 100 mM INR, a dose of
      290 kJ/m2 was needed in erythrocyte lysates and 100 kJ/m2 in intact red blood
      cell suspension. Measurements of absorption spectra showed that in all systems
      studied (NO-Hb in solution, intact erythrocytes and hemolysed erythrocytes) NO-Hb
      concentration decreased after irradiation by 14-22% with simultaneous formation
      of methemoglobin. These observations show that NO-Hb may serve as a store of
      nitric oxide from which free NO can be released by intensive illumination.

PMID- 11332879
TI  - Hydrogen peroxide is responsible for UVA-induced DNA damage measured by alkaline
      comet assay in HaCaT keratinocytes.
AB  - We investigated the role of different reactive oxygen species (ROS) in
      ultraviolet A (UVA)-induced DNA damage in a human keratinocyte cell line, HaCaT.
      UVA irradiation increased the intracellular levels of hydrogen peroxide (H2O2),
      detected by a fluorescent probe carboxydichlorodihydrofluorescein, and caused
      oxidative DNA damage, single strand-breaks and alkali-labile sites, measured by
      alkaline single cell gel electrophoresis (comet assay). Superoxide anion (O2*-)
      was a likely substrate for H2O2 production since diethyldithiocarbamate (DDC), a
      superoxide dismutase blocker, decreased the level of intracellular H2O2. Hydrogen
      peroxide was shown to play a central role in DNA damage. Increasing the
      intracellular levels of H2O2 with aminotriazole (AT) (a catalase blocker) and
      buthionine sulfoximine (BSO) (an inhibitor of glutathione synthesis) potentiated
      the UVA-induced DNA damage. Exogenous H2O2 was also able to induce DNA damage.
      Since H2O2 alone is not able to damage DNA directly, we investigated the
      significance of the H2O2-derived hydroxyl radical (*OH). Addition of FeSO4, that
      stimulates *OH formation from H2O2 (Fenton reaction) resulted in a twofold
      increase of DNA-damage. Desferrioxamine, an iron chelator that blocks the Fenton
      reaction, prevented UVA-induced DNA damage. We also employed a panel of less
      specific antioxidants and enzyme modulators. Sodium selenite (Na-Se) present in
      glutathione peroxidase and thioredoxin reductase and addition of glutathione
      (GSH) prevented DNA-damage. Tocopherol potently prevented UVA-and H2O2-induced
      DNA damage and reduced intracellular H2O2 -levels. Ascorbic acid reduced H2O2
      production, but only partly prevented DNA damage. Singlet oxygen (1O2) did not
      seem to play an important role in the UVA-induced DNA-damage since the specific
      1O2 scavenger sodium azide (NaN3) and the less specific 1O2 scavenger beta
      carotene did not markedly prevent either DNA-damage or H2O2 production. In
      conclusion the conversion of H2O2 to *OH appears to be the most important step in
      UVA-induced generation of strand breaks and alkali-labile sites and the bulk H2O2
      appears to originate from O2*- generated by UVA irradiation.

PMID- 11332880
TI  - Carotenoid triplet state lifetimes.
AB  - Carotene and xanthophyll triplet lifetimes are found to depend on the
      concentration of the parent molecule. These results account for some of the
      variations in carotenoid triplet lifetimes reported previously. The rate
      constants obtained for ground state quenching correlate with the number of
      conjugated double bonds, the longer chain systems having higher quenching rate
      constants.

PMID- 11332881
TI  - Fluorescence and photochemical characterization of phytochromes A and B in
      transgenic potato expressing Arabidopsis phytochrome B.
AB  - Phytochrome in etiolated sprouts of wild type (WT) potato and its transgenic
      strains (DARA5 and DARA12) expressing Arabidopsis thaliana phytochrome B (phyB)
      was investigated using low-temperature (85 K) fluorescence spectroscopy and
      photochemistry. Phytochrome content, [Ptot], position of the Pr emission and
      excitation spectra, lambda(max), and extent of the Pr-->lumi-R, gamma1, and Pr-
      >Pfr, gamma2, phototransformations (at 85 and 273 K, respectively) were shown to
      vary in the transgenic lines and WT depending on tissue used (upper vs. lower
      parts of etiolated sprouts) and light-induced phytochrome depletion. Differences
      in the parameters between the transgenic lines and WT were detected which were
      interpreted in terms of the two phenomenological Pr types: a labile Pr' with
      gamma1 approximately 0.5 consisting of a major phytochrome A (phyA) fraction
      (phyA') and a relatively conserved Pr" with gamma1 = 0 comprising a minor phyA
      fraction (phyA") and phyB. Both DARA lines had higher [Pr"] as compared with WT
      in the lower parts of etiolated stems, especially after light-induced phytochrome
      depletion (residual phytochrome in DARA5 and DARA12 made up to one-third of its
      initial level vs. <5% in WT). These differences were associated with the
      expression of Arabidopsis phyB in the DARA lines and its higher light stability
      than that of phyA. Arabidopsis phyB expressed in potato was characterised by
      lambda(max) = 683/669 nm in the emission/excitation (absorption) spectra and
      gamma1 = 0. PhyB also revealed a relatively low gamma2 (approx. 0.5) and its
      early red drop as compared with the gamma2 wavelength dependence for phyA. This
      is believed to contribute to the lower signalling ability of phyB and to confine
      the region (red) of its physiological activity.

PMID- 11332882
TI  - Photoactivity tests of TiO2-based inorganic sunscreens. Part 1: Non-aqueous
      dispersions.
AB  - A new method of measuring photoactivity of a major group of inorganic sunscreens
      (coated titanium dioxide) is presented based on the photobleaching of the radical
      1,1-diphenyl-2-picrylhydrazyl.

PMID- 11332883
TI  - The solid-state E/Z-photoisomerization of 1,2-dibenzoylethene .
AB  - The E/Z-photoisomerization of trans-1,2-dibenzoylethene (DBE) in the confinement
      of its crystal lattice proceeds readily, but not as a single crystal to single
      crystal process which was claimed previously by others. This model for the Z-->E
      isomerization at the 11-12 double bond of the retinal moiety in the crystal-like
      confinement of rhodopsin was investigated in view of the fact that the precise
      geometric features are crucial for a better understanding of the postulated twist
      mechanism. Atomic force microscopy (AFM) monitored long-range anisotropic
      molecular movements if trans-DBE was photoisomerized, but cis-DBE was unreactive
      even at the extreme sensitivity of AFM. The crystal lattices of both isomers
      cannot accommodate a rotational mechanism but at best the twist mechanism with
      the large groups not leaving their planes. The unidirectional solid-state
      photochemistry derives from the crystal packing of cis-DBE which exhibits severe
      3D-interlocking. Thus, trans-DBE molecules are not formed in the cis-lattice,
      because their moving away would be prohibited. Conversely, photochemically formed
      cis-DBE molecules escape the foreign trans-DBE lattice easily along its glide
      planes, as is experimentally observed by AFM. These findings are reminiscent of
      the escape of 11-trans-retinal from the rhodopsin array in the vision cascade.

PMID- 11332884
TI  - Polylysine-porphycene conjugates as efficient photosensitizers for the
      inactivation of microbial pathogens.
AB  - Porphycenes are electronic isomers of porphyrins which, when neutral, display no
      appreciable photosensitizing action towards Gram-negative bacteria. The covalent
      binding of oligomeric polylysine moieties, which are cationic at physiological pH
      values, endows porphycenes with a significant phototoxic activity against Gram
      negative bacteria while retaining their photoefficiency against a variety of
      microbial pathogens, including Gram-positive bacteria, fungi and mycoplasmas. The
      effect of the polylysine moiety is dependent on both the polylysine concentration
      and the degree of oligomerization. A suitable interplay among the various
      parameters opens the possibility to obtain either a broad spectrum of
      antimicrobial activity or a selective action toward a specific pathogen while
      minimizing the damage to human fibroblasts.

PMID- 11332885
TI  - Preparation of a water-soluble fluorinated zinc phthalocyanine and its effect for
      photodynamic therapy.
AB  - An amphiphilic fluorinated phthalocyanine, zinc
      tetracarboxyoctafluorophthalocyanine (ZnC4F8Pc) was synthesized and
      characterized. Its photodynamic efficiency for HeLa cells was compared with
      hydrophilic zinc octacarboxyphthalocyanine (ZnC8Pc) and hydrophobic zinc
      hexadecafluorophthalocyanine (ZnF16Pc). ZnC4F8Pc had a remarkable photodynamic
      effect among the phthalocyanines used. The effect is apparently caused by the
      fact that ZnC4F8Pc is mainly accumulated in the hydrophobic lipid membrane and is
      in the photoactive monomer form in HeLa cells.

PMID- 11332886
TI  - Protein flexibility as revealed by fluorescence resonance energy transfer: an
      extension of the method for systems with multiple labels.
AB  - The temperature profile of the normalized fluorescence resonance energy transfer
      efficiency is capable of monitoring the relative change of flexibility and/or
      conformational state of macromolecules [Biochemistry 23 (1984) 3403]. The method
      described earlier for one donor-one acceptor systems is extended to multiple
      fluorophore systems when the energy transfer occurs between either one donor-m
      acceptors, or n donors-one acceptor or n donors-m acceptors (where n and m are
      integer values). It is shown that the normalized energy transfer efficiency
      obtained for systems containing multiple labels is a linear combination of the
      normalized transfer efficiency assigned to individual donor-acceptor pairs of the
      system, thus its temperature profile is capable of monitoring the change of
      intramolecular flexibility and/or conformational state.

PMID- 11332887
TI  - Laser pretreatment protects cells of broad bean from UV-B radiation damage.
AB  - In order to determine the role of lasers in the stress resistance of broad bean
      (Vicia faba L.) to ultraviolet-B (UV-B) radiation, the embryos in seeds were
      exposed to He-Ne laser or CO2 laser radiation. Afterwards they were cultivated in
      Petri dishes in a constant temperature incubator until the lengths of epicotyls
      were nearly 3 cm. The epicotyls were then exposed to 1.02, 3.03 or 4.52 kJ m(-2)
      UV-B radiation, respectively, under 70 micromol m(-2) s(-1) photosynthetically
      active radiation (PAR) in a growth cabinet. Changes in the concentration of
      malondialdehyde (MDA), ascorbic acid (AsA) and UV-B absorbing compounds
      (absorbance at 300 nm) were measured to test the effects of laser pretreatment.
      The results showed that laser pretreatment of embryos enhanced UV-B stress
      resistance in the epicotyls of the broad bean by decreasing the MDA concentration
      and increasing the content of AsA and UV-B absorbing compounds. We suggest that
      those changes in MDA, AsA and UV-B absorbing compounds were responsible for the
      increase in stress resistance observed in the broad bean. This is the first
      investigation reporting the use of laser pretreatment to protect the cells of the
      broad bean from UV-B-induced damage.

PMID- 11332888
TI  - Tryptophan fluorescence quenching by alkaline earth metal cations in deionized
      bacteriorhodopsin.
AB  - Tryptophan quenching by the addition of alkaline earth metal cations to deionized
      bacteriorhodopsin suspensions was determined. The results show that the addition
      of cation primarily quenches fluorescence from surface tryptophan residues. The
      quenched intensity exhibits a 1/R dependence, where R is the ionic radius of the
      corresponding metal ion. This observation results from a stronger energy transfer
      coupling between the tryptophan and the retinal. The membrane curvature may be
      involved as a result of cations motion and correlated conformational changes.

PMID- 11332889
TI  - Organization of mixed monomolecular layers formed with the xanthophyll pigments
      lutein or zeaxanthin and dipalmitoylphosphatidylcholine at the argon-water
      interface.
AB  - Two-component monomolecular layers were formed with two xanthophyll pigments,
      lutein and zeaxanthin and dipalmitoylphosphatidylcholine (DPPC), at the argon
      water interface. Analysis of the mean molecular area parameters versus molar
      fraction of the xanthophyll component shows large overadditivity (ca. 50 A2 in
      the case of zeaxanthin and 150 A2 in the case of lutein) in the region of low
      molar fractions of carotenoids (maximum at 5 mol% in the case of zeaxanthin and
      at 20 mol% in the case of lutein). The experimental values of a mean molecular
      area are in good agreement with the values expected, based on the additivity rule
      at high molar percentages of the xanthophylls. Absorption spectroscopy of a
      single monolayer at the argon-water interface in the UV-Vis region has also been
      applied to analyze the formation of molecular assemblies of lutein in
      monomolecular films. The differences in the organization of lutein-DPPC and
      zeaxanthin-DPPC monolayers are interpreted in terms of the aggregation of
      xanthophyll pigments in the layers and different orientation of both xanthophylls
      at the interface. The results are discussed in relation to possible physiological
      functions of lutein and zeaxanthin in the membranes of the retina of an eye.

PMID- 11332890
TI  - Photoprotection in tadpoles of the common frog, Rana temporaria.
AB  - The common frog, Rana temporaria, spawning at altitudes up to 2600 m, is
      potentially threatened by UVB radiation. In laboratory experiments we found a
      specifically UVB absorbing substance (UVAS) in the skin of tadpoles with maximum
      absorption between 290 and 300 nm. The production of UVAS is induced by both
      visible light and ultraviolet radiation. The concentrations of UVAS found in
      tadpoles from the field are about as high as those found in tadpoles from
      laboratory experiments with UVB radiation under simulated mid-summer conditions.
      The existence of two powerful sun screen factors (UVAS and melanin pigmentation)
      may explain the high resistance of R. temporaria tadpoles to the intensive UVB
      radiation at high altitudes.

PMID- 11332891
TI  - UV radiation effects on flavocytochrome b2 in dilute aqueous solution.
AB  - A dilute aqueous solution of flavocytochrome b2 when exposed to inactivating
      doses of UV radiation at 280 nm underwent reversible loss in activity both under
      aerated and deaerated conditions. The active site as well as the substrate
      binding sites were found to be modified in the irradiated enzyme. Irradiation of
      the enzyme in the UV-C range resulted in partial unfolding of the polypeptide
      framework. Destruction and/or modification of both tryptophan and tyrosine
      residues as well as heme moieties took place. Preliminary laser flash photolysis
      studies suggest that the initial photo-ionization takes place with tryptophan and
      tyrosine residues with the formation of excited states and radicals, and then
      rapid transfer of electrons takes place to histidyl and cystinyl sites which
      might have eventually been altered in the process.

PMID- 11332892
TI  - Outdoor ultraviolet polychromatic action spectra for growth responses of Bellis
      perennis and Cynosurus cristatus.
AB  - Polychromatic ultraviolet (UV) action spectra for various growth responses of the
      dicotyledon Bellis perennis L. (daisy) and the grass Cynosurus cristatus L.
      (crested dog's-tail) have been measured. The plants were grown in the natural
      environment and ambient daylight was supplemented with five different UV
      irradiances centred at eight different wavelengths (313, 318, 320, 322, 339, 348,
      356 and 377 nm). Destructive growth analysis was performed on B. perennis and C.
      cristatus after 300 and 122 days respectively. Dose response curves were created
      to construct action spectra for individual responses. Different spectral
      responses were observed in these two plant types. B. perennis exhibited a
      substantial action maximum at 313 nm for the inhibition of aerial, root and total
      dry weight; a similar action maximum at 313 nm for the inhibition of leaf
      expansion was observed. Longer wavelengths were relatively ineffective on these
      growth parameters, with the exception of a small but statistically significant (P
      < 0.05) response to 320 nm radiation. By contrast, C. cristatus showed negligible
      response to 313 nm radiation, for inhibition of aerial, root and total dry weight
      but substantial responses to longer wavelengths, especially at 339 and 348 nm.
      These action spectra add weight to suggestions in the literature that UV-A has a
      role to play in responses in this region of the spectrum. The possible
      implications of these observations are discussed.

PMID- 11332893
TI  - Biosynthesis and photodynamic efficacy of protoporphyrin IX (PpIX) generated by 5
      aminolevulinic acid (ALA) or its hexylester (hALA) in rat bladder carcinoma
      cells.
AB  - Hexylester of 5-aminolevulinic acid (hALA) has been considered as an alternative
      to 5-aminolevulinic acid (ALA) for the treatment of malignancies of different
      origin. The present study addresses the ALA and hALA-induced PpIX pharmacokinetic
      profile using rat bladder carcinoma cells (AY27). The total PpIX content measured
      spectrofluorimetrically after extraction procedure at the end of 2 h incubation
      was at least 1.5-fold greater with hALA compared to ALA despite the difference in
      concentration of several orders between the two compounds (1 or 5 mM ALA and 5 or
      10 x 10(-3) mM hALA). Considerable PpIX efflux was detected in the extracellular
      medium at the end of the incubation. With 5 mM ALA and 10 x 10(-3) mM hALA, PpIX
      build-up was continued beyond the incubation period pointing out to enzyme
      saturation in the biosynthetic pathway or/and the constitution of ALA reserve.
      Red laser light (lambda=630 nm) irradiation of AY27 cells after 2 h incubation
      with increasing ALA or hALA concentrations resulted in a nearly equal
      photocytotoxicity.

PMID- 11332894
TI  - The 5-aminolaevulinic acid-based photodynamic effects on nuclei and nucleoli of
      HL-60 leukemic granulocytic precursors.
AB  - To provide more information on the 5-aminolaevulinic acid (ALA)-based
      photodynamic effect (PDE) on nuclei and nucleoli of individual leukemic cells,
      these structures were studied in cultured HL-60 cells which originated from
      leukemic highly immature and less differentiated precursors of granulocytes. The
      nuclear morphology was visualized by panoptic May-Grunwald/Giemsa staining and
      cytochemical method for DNA, nucleoli were visualized by cytochemical methods for
      the demonstration of RNA and silver stainable proteins including those of
      interphase silver stained nucleolus organizer regions (AgNORs). In most cells ALA
      based photodynamic treatment (PDT) produced marked alterations such as formation
      of apoptotic bodies, and large condensation of nuclear chromatin structure but
      without nuclear segmentation. Such changes are in harmony with the apoptotic
      process induced in these cells but without previous terminal differentiation. In
      nucleoli ALA-based PDT produced the reduction and disappearance of nucleolar
      silver stainable particles (SSPs) representing AgNORs which apparently reflected
      the alteration of the nucleolar biosynthetic activity and cell proliferation. The
      latter is also reflected by the disappearance of mitotic divisions. On the other
      hand, a small subpopulation of cells was less sensitive or resistant to the ALA
      based PDE since they did not show mentioned nuclear and nucleolar alterations.

PMID- 11332895
TI  - Fabrication and photoelectric properties of self-assembled bilayer lipid
      membranes on conducting glass.
AB  - Supported bilayer lipid membranes (s-BLMs with and without the doping of
      fullerene C60) self-assembled on indium-tin oxide (ITO) glass were fabricated and
      characterized by cyclic voltammetry and electrochemical impedance spectroscopy
      using a three-electrode system. The photoelectric properties of the ITO supported
      planar lipid bilayers were studied. Light intensity of irradiation, bias voltage,
      and concentration of donors have been found to be limiting factors of the
      transmembrane photocurrent. The facilitation effect of C60 doping in s-BLMs on
      the photoinduced electron transfer across s-BLM is discussed. This novel self
      assembled ITO/s-BLM system may provide a simple and mechanically stable model for
      the study of the photoelectric and photodynamic properties of biomembranes.

PMID- 11332896
TI  - Fluorescence-labelled DNA probes to detect complementary sequences in homogeneous
      media.
AB  - Sensitive, safe and easy-to-use probes for the detection of nucleic acids are
      urgently called for. To this end we are in the process of developing a
      fluorescence-based technique to work in homogeneous assay media. We have examined
      pyrene and fluorescein as fluorescent labels for natural DNA probes. A fraction
      of the cytosine residues of a single-stranded cDNA was randomly labelled with
      either pyrene or fluorescein using the bisulfite-catalyzed diamine reaction. Both
      fluorophores showed fluorescence quenching when the labelled probe was hybridized
      with its complementary strand and we describe the changes in steady-state
      fluorescence intensity that occurred upon hybridization. Our results demonstrate
      that pyrene quenching is more efficient than fluorescein quenching and thus
      pyrene-labelled probes are more sensitive for detecting and quantifying DNA from
      natural sources.

PMID- 11332897
TI  - Mitochondrial localization and photodamage during photodynamic therapy with
      tetraphenylporphines.
AB  - The subcellular localization sites of TPPS4 and TPPS1 and the subsequent cellular
      site damage during photodynamic therapy were investigated in CT-26 colon
      carcinoma cells using spectroscopic and electron microscopy techniques. The
      association of both porphyrins with the mitochondria was investigated and the
      implications of this association on cellular functions were determined.
      Spectrofluorescence measurements showed that TPPS4 favors an aqueous environment,
      while TPPS1 interacts with lipophilic complexes. The subcellular localization
      sites of each sensitizer were determined using spectral imaging. Mitochondrial
      CFP transfected cells treated with porphyrins revealed localization of TPPS1 in
      the peri-nuclear region, while TPPS4 localized in the mitochondria, inducing
      structural damage and swelling upon irradiation, as shown by transmission
      electron microscopy. TPPS4 fluorescence was detected in isolated mitochondria
      following irradiation. The photodamage induced a 38% reduction in mitochondrial
      activity, a 30% decrease in cellular ATP and a reduction in Na(+)/K(+)-ATPase
      activity. As a result, cytosolic concentrations of Na(+) and Ca(2+) increased,
      and the level of K(+) decreased. In contrast, the lipophilic TPPS1 did not affect
      mitochondrial structure or function and ATP content remained unchanged. We
      conclude that TPPS4 induces mitochondrial structural and functional photodamage
      resulting in an altered cytoplasmic ion concentration, while TPPS1 has no effect
      on the mitochondria.

PMID- 11332898
TI  - Antibiotic prescribing practices in a teaching clinic: comparison of resident and
      staff physicians.
AB  - BACKGROUND: The widespread and often inappropriate use of broad spectrum
      antibiotics in the outpatient setting is recognized as a significant contributing
      factor to the spread of bacterial resistance. We hypothesized that residents
      prescribe broader spectrum antibiotics more frequently than staff physicians and
      adopt more appropriate prescribing practices with increasing levels of training.
      METHODS: All patient visits for acute sinusitis in our teaching practice between
      July 1, 1995, and June 30, 1997, were reviewed. Comparisons of antibiotics
      prescribed were made between staff and residents at each level of training.
      RESULTS: First- and second-year residents were more likely to prescribe narrow
      spectrum antibiotics (56%) than third-year residents (35%) or staff (34%).
      CONCLUSIONS: Junior residents in our program are more likely to prescribe narrow
      spectrum antibiotics for the treatment of acute sinusitis than are senior
      residents or staff. With advancement in level of training, prescribing practices
      of residents come to resemble those of their supervising staff physicians.

PMID- 11332899
TI  - Recognizing, reporting, and reducing adverse drug reactions.
AB  - Adverse drug reactions (ADRs) are underreported and consequently are an
      underestimated cause of morbidity and mortality. Recent epidemiologic evidence
      estimates that ADRs represent the fourth to the sixth leading cause of death.
      Public awareness is increasing as reports of ADRs and medication errors become
      more prevalent in the lay press. Reducing the number of ADRs can be accomplished
      by systems changes made at an individual and national level. At the individual
      level, increased diligence should be used with regard to reporting and
      documenting ADRs. At the national level, ADRs can be reduced by expanding the
      role of the arm of the Food and Drug Administration (FDA) responsible for
      postmarketing surveillance.

PMID- 11332900
TI  - Religion in the clinic: the role of physician beliefs.
AB  - BACKGROUND: Although studies have identified physician beliefs that may cause
      them to avoid spiritual topics in the clinic (eg, lack of time), it is unknown to
      what extent these beliefs predict behavior. The purpose of the present study was
      to identify physician beliefs about religion and medicine that predict attention
      to religious issues in the clinic. METHODS: The study was cross-sectional and
      correlational. Seventy-eight physicians completed a self-report survey of
      religious behavior in the clinic and beliefs about religion and medicine.
      RESULTS: Most physicians do not initiate religious discussions with patients,
      though a majority accept a link between religion and health. Physician personal
      discomfort with addressing religious topics was the sole multivariate predictor
      of clinical religious behavior. Time, role definition, health relevance of
      religion, and physician religiousness were not significant predictors.
      CONCLUSIONS: Avoidance of religion in the clinic may be primarily belief-based.
      Future research is needed to examine the role of medical education in creating
      and/or maintaining these beliefs.

PMID- 11332901
TI  - Traumatic pseudoaneurysm of the thyrocervical trunk.
AB  - A case of a pseudoaneurysm of the thyrocervical trunk after a pocketknife stab
      wound to zone I of the neck is reported. The patient was evaluated and treated in
      an emergency department with irrigation of the wound, bandage, and oral
      antibiotics. A large pseudoaneurysm slowly developed over the next 2 months. When
      the patient arrived at our hospital, he was immediately admitted and arteriograms
      were obtained. Arteriograms revealed an active leak of blood into a
      pseudoaneurysm from the thyrocervical trunk. Surgical treatment consisted of
      proximal and distal ligation of the thyrocervical trunk. This is the first case
      of a pseudoaneurysm developing only from the thyrocervical trunk due to a stab
      wound to zone I of the neck. This case and its complication serve to illustrate
      and emphasize the rationale for routinely imaging the great vessels after all
      penetrating trauma to zone I of the neck.

PMID- 11332902
TI  - Open scapulothoracic dissociation.
AB  - Scapulothoracic dissociation refers to the traumatic separation of the shoulder
      from the chest wall. This most commonly occurs as a closed injury. We present a
      case of open scapulothoracic dissociation and emphasize clinical features unique
      to this injury. In both closed and open scapulothoracic dissociation, the force
      necessary to shear the scapula from its thoracic attachments results in vascular
      disruption and neurologic injury to the upper extremity. As a consequence,
      patients have a pulseless, flail upper extremity with a significant chest wall
      hematoma (closed) or active bleeding (open). The first priority is to resuscitate
      and address life-threatening injuries. If the patient has active bleeding,
      immediate vascular control to prevent exsanguination is essential. Patients with
      ischemia and an incomplete injury or unreliable neurologic examination need
      revascularization. Outcome is based on the extent of brachial plexus or cervical
      nerve root avulsion. Patients with loss of neurologic function ultimately benefit
      from amputation at the appropriate level.

PMID- 11332903
TI  - Gray ramus communicans nerve block: novel treatment approach for painful
      osteoporotic vertebral compression fracture.
AB  - BACKGROUND: Osteoporotic vertebral compression fracture (OVCF) is a common
      complication of osteoporosis in the aging population. Refractory chronic pain may
      develop, and few effective treatment options exist. METHODS: We retrospectively
      analyzed 52 cases in which gray ramus communicans nerve block was used for
      painful OVCF after failure of conservative analgesic therapy. All were office
      based, fluoroscopically guided procedures; a combination of 2% lidocaine and 2%
      sterile triamcinolone diacetate (Aristocort) was injected on the gray ramus tract
      of the somatic nerve root corresponding with radiographically documented OVCF.
      Patient-reported and physician-reported pain scores, analgesic medication use,
      and overall patient satisfaction were measured. The average follow-up period was
      9 months. RESULTS: A 1-point improvement in pain scores was reported by 92% of
      patients and 88% of physicians; a 4-point improvement was reported by 63% and
      58%, respectively. No patients reported increased pain scores; physicians
      reported increases in two cases. Decreased analgesic requirement was documented
      in 42%. Patient satisfaction was "high" in 50% and "medium" in 25%. No procedural
      complications occurred. CONCLUSION: Prompt and sustained improvements in all
      parameters, especially pain scores, support widespread clinical application of
      this safe effective and cost-effective therapy.

PMID- 11332904
TI  - Prophylactic and therapeutic fixation of weight-bearing long bones with
      metastatic cancer.
AB  - BACKGROUND: We retrospectively studied the duration of operations and the
      hospitalizations for impending and manifest fractures of weight-bearing long
      bones with metastatic disease, which has rarely been done. METHODS: The duration
      of operative fixation and the hospital stay in patients with an impending (n = 7)
      or actual (n = 15) fracture in a weight-bearing long bone with metastatic tumor
      were assessed, including symptomatic response, posttreatment mobility, and
      survival rate. RESULTS: Most patients had significant relief of pain. More than
      half of patients with impending fracture and 80% with actual fracture were
      ambulatory after therapy; 3-year survival rates were 29% and 13%, respectively.
      Corresponding mean durations for the operations were 175 minutes and 185 minutes,
      respectively; mean durations of hospitalization were 22 days and 16 days,
      respectively. CONCLUSION: Surgical fixation of fractures in weight-bearing long
      bones with metastatic cancer does not require excessive operative time as
      compared with that of impending fractures, does not extend hospitalization, and
      has an acceptable risk-reward ratio.

PMID- 11332905
TI  - Human immunodeficiency virus infection in elderly patients.
AB  - BACKGROUND: The proportion of older individuals infected with the human
      immunodeficiency virus (HIV) is rising. METHODS: We performed a retrospective
      case-control study of 58 patients more than 60 years old at the time of diagnosis
      of HIV infection and compared them with 232 controls (matched by CD4+ lymphocyte
      count). Clinical and demographic data were obtained from the Adult Spectrum of
      Diseases (ASD) database at the Medical Center of Louisiana. RESULTS: Patients in
      the older age group were more likely to be male and African American or Hispanic.
      The most common risk factor for acquisition of HIV infection among the patients
      was homosexual contact (53%). Disease staging was similar in both groups as
      determined by CD4+ lymphocyte counts and history of opportunistic infections.
      There was no difference in the use of antiretroviral therapy. In a Cox
      proportional hazard model and regression models, age > or = 60 years was
      associated with shorter survival. CONCLUSION: Patients who are older than 60
      years at the time of diagnosis of HIV infection have a shorter survival than
      younger patients.

PMID- 11332906
TI  - Prevalence of penicillin-nonsusceptible Streptococcus pneumoniae in
      nasopharyngeal cultures from patients with sickle cell disease.
AB  - BACKGROUND: Prevention of pneumococcal sepsis in children with sickle cell
      disease (SCD) is threatened by the emergence of penicillin-nonsusceptible
      pneumococci. METHODS: In this study, nasopharyngeal colonization with
      Streptococcus pneumoniae and penicillin susceptibility were compared in children
      with SCD and a control group. Nasopharyngeal cultures were obtained from 130
      children with SCD and 123 control children. Penicillin susceptibility was
      determined by Epsilometer test. Compliance with penicillin prophylaxis in SCD
      patients was determined by parent interviews and review of patients' medical and
      pharmacy records. RESULTS: Streptococcus pneumoniae was isolated from 8 (6%) of
      130 SCD patients, and 21 (17%) of 123 control patients. Of the 29 S pneumoniae
      isolates, 6 (21%) were nonsusceptible to penicillin; 4 of 8 (50%) were from the
      SCD group and 2 of 21 (10%) from the control group. CONCLUSIONS: Penicillin
      prophylaxis decreased the rate of S pneumoniae colonization in SCD patients;
      however, it also increased the risk of selective colonization with penicillin
      nonsusceptible S pneumoniae.

PMID- 11332907
TI  - Congenital vascular lesions of the gastrointestinal tract: blue rubber bleb nevus
      and Klippel-Trenaunay syndromes.
AB  - We present two cases of hemangiomatosis of the gastrointestinal tract. The first
      case describes a 59-year-old patient with upper gastrointestinal hemorrhage due
      to the blue rubber bleb nevus syndrome. The second case illustrates a 26-year-old
      patient with recurrent rectal bleeding due to Klippel-Trenaunay syndrome. These
      two syndromes are distinct disorders characterized by cavernous hemangiomas of
      the skin, soft-tissue, bones, and viscera. In addition, we review the available
      literature on the epidemiology, transmission, clinical features, associated
      conditions, diagnosis, and treatment of these two disorders.

PMID- 11332908
TI  - Quality vascular surgical care: the importance of innovation and change in an era
      of dwindling reimbursement.
AB  - BACKGROUND: Reductions in vascular surgery reimbursement emphasize the need to
      decrease cost while maintaining quality. Hospital solvency is essential if we are
      to preserve acceptable levels of nursing/support personnel and acquire new
      diagnostic and treatment programs. METHODS: Care processes for patients
      undergoing carotid, aortic, or dialysis access surgery were retrospectively
      analyzed and new quality- and cost-oriented treatment algorithms and clinical
      pathways were developed and implemented using case management principles.
      Preoperative risk stratification, length of stay, costs, complications, outcomes,
      and patient satisfaction were compared before and after these revisions in the
      care process. Statistical analyses were done using the Wilcoxon Rank sum test and
      Fisher exact test. RESULTS: Significant reductions in length of stay, intensive
      care use, and cost of treatment and diagnosis were achieved without adversely
      affecting morbidity, mortality, or patient satisfaction. CONCLUSION: Use of
      algorithm, clinical pathway, and case management principles resulted in a marked
      improvement in the "bottom line" for vascular surgical procedures in our academic
      medical center.

PMID- 11332909
TI  - Reactive and clonal thrombocytosis: proinflammatory and hematopoietic cytokines
      and acute phase proteins.
AB  - BACKGROUND: We quantitated proinflammatory and thrombopoietic cytokines in
      reactive thrombocytosis (RT) and clonal thrombocytosis (CT) to identify a
      cytokine profile that might aid in the distinction of these two disorders.
      METHODS: Serum levels of cytokines relevant to platelet biology--interleukins 3,
      6, 11, and 1beta; thrombopoietin; tumor necrosis factor alpha; and C-reactive
      protein (CRP)--were measured by enzyme-linked immunosorbent assay in healthy
      subjects and in patients with CT and RT. RESULTS: Interleukin-6 and CRP levels
      were higher in RT patients than in controls or CT patients. Interleukin 1beta
      levels were higher in the RT group than in the CT and control groups.
      CONCLUSIONS: In RT, IL-6, IL-1beta, and CRP levels are elevated. In both RT and
      CT, IL-11 is elevated, but thrombopoietin levels are not.

PMID- 11332910
TI  - Human immunodeficiency virus seroprevalence trends: five hospitals in south
      Georgia, 1993 through 1997.
AB  - BACKGROUND: Human immunodeficiency virus (HIV) seroprevalence surveys help
      determine the extent of HIV and the need for routine HIV counseling and testing.
      We sought to describe trends in five south Georgia hospitals and compare two
      protocols for conducting anonymous HIV surveys. METHODS: From 1993 to 1997, each
      hospital tested approximately 1,400 anonymous, leftover blood specimens per year.
      Two hospitals (C and E) tested all specimens, and three hospitals (A, B, and D)
      excluded blood known to be HIV-related. RESULTS: The mean HIV seroprevalence at
      hospitals C and E was between 2.0% and 2.3% each year. The mean HIV
      seroprevalence at hospitals A, B, and D increased from 0.5% to 1.0% during 1993
      to 1995, then decreased to 0.3% in 1997. CONCLUSIONS: In hospitals C and E, the
      level of HIV disease was constant. In hospitals A, B, and D, the HIV
      seroprevalence decreased to 0.3%, suggesting that routine HIV counseling and
      testing is not currently needed in these hospitals. Hospitals should consider
      conducting periodic anonymous HIV seroprevalence surveys, sampling from all
      patients and distinguishing between specimens known to be HIV-related and those
      that are not.

PMID- 11332911
TI  - Endocarditis due to Salmonella.
AB  - We present a case of endocarditis caused by Salmonella in a patient with newly
      diagnosed diabetes and preexisting rheumatic heart disease. Despite sterilization
      of the blood with a fluoroquinolone and a third-generation cephalosporin, the
      patient required surgical intervention.

PMID- 11332912
TI  - Isolated septic arthritis caused by penicillin-resistant Streptococcus
      pneumoniae.
AB  - Streptococcus pneumoniae is a common cause of infection in the pediatric
      population, as well as an important cause of septic arthritis. The increased
      prevalence of drug-resistant S pneumoniae in North America has renewed interest
      in the use of pneumococcal vaccines. We describe the case of a child with
      isolated acute septic arthritis caused by infection with penicillin-resistant S
      pneumoniae.

PMID- 11332913
TI  - Noonan's syndrome and seminoma of undescended testicle.
AB  - A 26-year-old white man with Noonan's syndrome and a history of lifetime
      lymphedema had had bilateral orchiopexy for undescended testicles at the age of
      12. He noticed increased swelling of the right testicle confirmed by
      ultrasonography as a solid mass. Computed tomography of the abdomen and pelvis
      showed multiple enlarged mesenteric and retroperitoneal lymph nodes. At right
      inguinal orchiectomy, pathologic findings were consistent with seminoma of the
      right testicle. Postoperatively, he was treated with four cycles of cisplatin and
      etoposide. A case of nonseminoma in Noonan's syndrome has been reported
      previously, but this is first case report of seminoma in a patient with Noonan's
      syndrome.

PMID- 11332914
TI  - Soft tissue and cartilage infection by Salmonella oranienburg in a healthy girl.
AB  - Focal extraintestinal infections from nontyphoid salmonellae have increased in
      incidence during the past decade. Typically, they are manifested as either
      osteomyelitis or meningitis as a complication of either bacteremia or enteric
      fever. Isolated salmonellal soft tissue infections, however, are rare and occur
      mostly in adults with chronic underlying conditions such as human
      immunodeficiency virus (HIV) infection, diabetes mellitus, and cell-mediated
      immunity defects. We report a case of an otherwise healthy adolescent who was
      exposed to a guinea pig with a skin mass. She subsequently had an isolated soft
      tissue infection with cartilaginous involvement of the anterior chest wall due to
      Salmonella enterica serogroup C1 (bioserotype oranienburg).

PMID- 11332915
TI  - Rothia dentocariosa endocarditis complicated by multiple intracranial
      hemorrhages.
AB  - Rothia dentocariosa is a gram-positive rod found commonly as part of the normal
      flora of the mouth. It rarely causes clinical disease. Subacute infective
      endocarditis has been the most commonly reported R dentocariosa infection, and
      extracardiac complications occur frequently. Solitary intracranial hemorrhages
      have been reported in two cases. We describe the first case of infective
      endocarditis complicated by the sequential and unusually prolonged development of
      multiple new intracranial hemorrhages.

PMID- 11332917
TI  - Subclavian steal syndrome: a rare but important cause of syncope.
AB  - An elderly woman came to our emergency room for evaluation of a syncopal episode.
      While climbing a flight of stairs, she had turned her head to the left and
      abruptly passed out. Positive physical findings included blood pressure of 141/65
      mm Hg (right arm) and 80/43 mm Hg (left arm), as well as nonpalpable left radial
      and brachial pulses that were detectable only by Doppler ultrasonography. Carotid
      duplex ultrasonography showed reverse flow in the left vertebral artery and an
      abnormal, stenotic distal left subclavian artery. Magnetic resonance angiography
      confirmed complete occlusion of the left subclavian artery with classic
      subclavian steal. The patient had percutaneous transluminal angioplasty with
      stenting of the left subclavian artery and has remained asymptomatic through 2
      years of follow-up with aggressive risk-factor modification.

PMID- 11332916
TI  - Mycotic aortic aneurysm in a patient with Tolosa-Hunt syndrome.
AB  - Mycotic aneurysms have been associated with many clinical conditions. A tender
      pulsatile abdominal mass in association with fever, chills, and unrelenting back
      pain is suggestive of a leaking mycotic aneurysm. However, the extracranial
      manifestations of Tolosa-Hunt syndrome (THS) may mimic several of these symptoms.
      We report the case of a woman who was successfully treated with high-dose
      steroids for THS. Two months later, she was admitted to another hospital with
      rigors and unremitting back and abdominal pain. CT-guided aspiration of an L5-S1
      paravertebral mass was done. The aspirate and blood cultures grew Staphylococcus
      aureus. Intravenous antibiotics and analgesics were administered with good
      relief. A month after discharge from that hospital, she was admitted to our
      hospital with classic signs and symptoms of a leaking mycotic aneurysm. She was
      treated surgically and has remained asymptomatic for 21 months. Tolosa-Hunt
      syndrome associated with mycotic aortic aneurysms has not been previously
      reported.

PMID- 11332918
TI  - CT halo sign in pulmonary metastases from mucinous adenocarcinoma of the
      pancreas.
AB  - The CT halo sign was first described in immunocompromised patients with invasive
      pulmonary aspergillosis. Although the halo sign was originally thought to be
      specific for invasive pulmonary aspergillosis, it has been reported in a wide
      variety of pulmonary abnormalities in both immununocompromised and
      immunocompetent patients. We report a case of mucinous adenocarcinoma of the
      pancreas metastatic to the lungs in which there were multiple pulmonary nodules
      showing the halo sign. This case further illustrates the nonspecific nature of
      the CT halo sign and the need to consider malignancy as a cause in
      immunocompetent patients.

PMID- 11332919
TI  - Androgen-producing, atypically proliferating endometrioid tumor arising in
      endometriosis.
AB  - A case of androgen-secreting borderline endometrioid tumor arising in
      endometriosis of the rectovaginal septum is presented. It occurred 10 years after
      total abdominal hysterectomy and bilateral salpingo-oophorectomy for extensive
      endometriosis of the fallopian tubes and ovaries, adenomyosis, and leiomyomas of
      the uterus. We believe 7 years of unopposed continuous oral estrogen replacement
      therapy contributed to the malignant transformation of the endometriosis.

PMID- 11332920
TI  - Urinary ascariasis in a man with hematuria.
AB  - We present a case believed to be the first reported North American presentation
      of Ascaris lumbricoides within the urogenital tract. A young man came to the
      emergency department because of painless hematuria and having observed a 6-inch
      worm exit his urethra while urinating. The most common site for A lumbricoides
      infection is the gastrointestinal tract, specifically the area of the
      hepatopancreatic ducts. Worldwide, A lumbricoides infections are ubiquitous, but
      infections outside the alimentary tract are extremely rare.

PMID- 11332921
TI  - Role of natriuretic hormones in the diagnosis of patent ductus arteriosus in
      newborn infants.
AB  - Haemodynamically significant patent ductus arteriosus worsens respiratory
      distress by initiating pulmonary congestion and inactivating of surfactant.
      Excepting size of the ductus, several factors influence ductal flow. CONCLUSION:
      Atrial natriuretic hormones provide clinically useful data, especially in serial
      follow-up of the patient.

PMID- 11332922
TI  - Meconium aspiration syndrome: a role for phospholipase A2 in the pathogenesis?
AB  - The pathophysiology of neonatal meconium aspiration syndrome (MAS), often
      resulting in severe respiratory failure, is complex and still largely unclear.
      Factors involved in the propagation of acute lung injury after perinatal
      aspiration of meconium include obstruction of the airways, ventilation/perfusion
      mismatch, increase of the pulmonary vascular resistance and a rapidly developing
      parenchymal and alveolar inflammatory reaction with associated surfactant
      dysfunction. CONCLUSION: Although the early pulmonary inflammatory response is
      believed to play a central pathogenetic role in the meconium-induced acute lung
      damage, its initiating mechanisms are still poorly defined. However, increasing
      evidence indicates a direct toxic effect of meconium.

PMID- 11332923
TI  - Parents' observations of sexual behaviour in pre-school children.
AB  - This commentary on the Larsson and Svedin study of sexual behaviour in pre-school
      children, published in the present issue of Acta Paediatrica, centres around
      three questions: 1. How can normal sexual behaviour in children be distinguished
      from problematic behaviour? 2. What characterizes the sexual development of the
      normal child? 3. Can knowledge about normal and problematic sexual behaviour be
      used to screen for sexual abuse or to confirm cases of sexual victimization? It
      is recommended that the inventory used by the authors be standardized on a
      representative sample of Swedish children, because this would enhance its
      usefulness in distinguishing normal from problematic behaviour. It is further
      recommended that research about sexual development in children be based on person
      oriented rather than on variable-oriented analyses. It is finally argued that
      knowledge about normal and problematic sexual behaviour may not contribute to
      more effective screening or confirmation procedures in suspicions of sexual
      abuse. However, knowledge about normal sexual behaviour is valuable in studies of
      sexual behaviour in different categories of children, e.g. in the developmentally
      delayed or psychosocially deprived. CONCLUSION: By helping to identify
      problematic sexual behaviour in individual children, a standardized inventory
      could guide professionals in detecting possible psychological problems
      accompanying the behaviour.

PMID- 11332924
TI  - Inguinal hernias in premature babies: wait or operate?
AB  - There are several contentious issues in the management of inguinal hernias in
      premature neonates. They include the timing of surgery, the management of
      incarceration, the role of routine contralateral groin exploration and the type
      of anaesthesia. In this article we re-emphasize the importance of delaying
      surgery until the baby is ready for discharge from the neonatal unit. Regular
      examinations and manual reduction of these hernias should be performed in order
      to detect incarcerations early. CONCLUSION: With this approach, it may be
      possible to minimize the morbidity resulting from incarceration, and at the same
      time avoid the respiratory and testicular complications resulting from an early
      surgical/anaesthetic intervention.

PMID- 11332925
TI  - Breast odour as the only maternal stimulus elicits crawling towards the odour
      source.
AB  - In previous studies, newborn infants placed on their mother's chest grasped a
      nipple and sucked without assistance. Furthermore, neonates sucked preferentially
      from an untreated breast rather than the alternative breast that had been washed
      to eliminate its natural odour. This study investigated the influence of breast
      odours per se on orientated physical movement of neonates. In total, 22 babies
      were observed during two trials on a warming bed. In one trial, a pad carrying
      the mother's breast odour was placed 17 cm in front of the baby's nose; in the
      other trial a clean pad was used. More babies moved towards and reached the
      breast pad than the clean pad. CONCLUSION: Natural breast odous unsupported by
      other maternal stimuli therefore appear to be sufficient to attract and guide
      neonates to the odour source.

PMID- 11332927
TI  - Growth tracks in early childhood.
AB  - AIM: Child growth is modulated by numerous factors and, particularly in infancy
      and early childhood, often tends to follow apparently irregular patterns, with
      many centiles crossed before the later growth channels are reached. The aim of
      this study was to visualize the diversity of individual growth. DESIGN: The study
      investigated 333 girls and 329 boys without chronic illnesses from four
      paediatric practices in Kiel, Germany. The children were measured on natural,
      i.e., on various occasions, when they were presented to their doctors for
      preventive care examinations and for minor illnesses, at the age of 0.25 (range
      +/- 0.08) y, 0.5 (range +/- 0.16) y, 0.75 (range +/- 0.16) y, 1.0 (range +/-
      0.25) y, and at the ages of 1.5, 2, 3, 4 and 5 (range +/- 0.25) y. Each
      individual growth curve was converted into a series of height SDS (standard
      deviation scores) using one of the most reputable longitudinal German growth
      studies as background reference. Height SDS was then converted into residual
      height SDS (differences between height SDS of each measurement and average
      personal height SDS of the respective child). Cluster analysis was used to
      identify groups of children (clusters) with similarities in residual height SDS
      patterns (growth tracks). The clusters contained a minimum of at least 10
      children. Single children or small sets of individuals below the minimum number
      were rejected from further analysis. RESULTS: In males, 10 growth tracks were
      identified, each consisting of 11 to 52 boys. Growth in 111 boys was so
      heterogeneous that they could not be assigned to growth tracks. In females, 11
      growth tracks were identified, each consisting of 12 to 48 girls; 112 girls could
      not be assigned. Approximately 7% of boys and 15% of girls showed evidence of a
      mild intermittent growth spurt at the end of infancy. Some growth tracks were
      almost horizontal, or showed declining residual height SDS up to the age of 3 and
      4 y, with no evidence of growth spurts during early childhood. Others showed
      sharply declining growth in early infancy, or irregular patterns. Similar results
      were obtained when using cross-sectional standards as background reference.
      CONCLUSION: Cluster analysis provides evidence that the substantial diversity in
      infant and early child growth, is limited to a small number of narrow but
      characteristic tracks of yet unknown biological significance.

PMID- 11332926
TI  - A randomized controlled clinical trial of zinc, vitamin A or both in
      undernourished children with persistent diarrhea in Bangladesh.
AB  - In a double-blind randomized controlled clinical trial, moderately malnourished
      Bangladeshi children (61-75% of the median weight/age) were studied for the
      effect of zinc and/or vitamin A supplementation on the clinical outcome of
      persistent diarrhea. Children 6 mo to 2 y of age with diarrhea for more than 14 d
      were randomly allocated into 4 groups of 24 receiving a multivitamin syrup and
      (i) zinc (20 mg elemental), (ii) vitamin A, (iii) both zinc and vitamin A, or
      (iv) neither, in 2 doses daily for 7 d. Clinical data on recovery and on stool
      output, consistency and frequency were recorded for 7 d, and weight change from
      day 1 to day 7 was assessed. The baseline characteristics of the four study
      groups were comparable. The mean daily stool outputs from days 2 to 7 of therapy
      were significantly less in the zinc and zinc plus vitamin A groups, but not in
      the vitamin A group, in comparison with the control group. In children receiving
      zinc, the cumulative stool weight in the 7 d was 39% less than in the control
      group (p < 0.001) and 32% less than in the vitamin A group (p = 0.006). The
      cumulative stool weight in the zinc plus vitamin A group was 24% less than in the
      control group (p < 0.001), but the 14% lower output than in the vitamin A group
      was not statistically different. The change in body weight over the 7 d study
      period was significantly different between the group receiving zinc and the
      control group (+111 g vs -90 g, p = 0.045). The rate of clinical recovery of
      children within 7 d was significantly greater in the zinc group (88%) compared
      with the control group (46%, p = 0.002) or vitamin A group (50%, p = 0.005), but
      not statistically different from the zinc plus vitamin A group (67%, p = 0.086).
      CONCLUSION: The results indicate that zinc, but not vitamin A, supplementation in
      persistent diarrhea reduces stool output, prevents weight loss and promotes
      earlier recovery.

PMID- 11332928
TI  - Body mass index, triceps skinfold and waist circumference in screening for
      adiposity in male children and adolescents.
AB  - Simple anthropometric measurements and indices are the most commonly used tools
      for assessing body composition. Only a few papers have examined the sensitivity
      and specificity of the body mass index (BMI) against total body fat percentage
      (TBF%) from underwater weighing in children and adolescents. The objective of the
      study was to evaluate the screening performance of BMI, triceps skinfold
      thickness and waist circumference for excess TBF%. A total of 175 healthy
      volunteer males, aged 7.0-16.9 y, participated in the study. TBF% was measured
      using underwater weighing as the reference method. Receiver operating
      characteristic (ROC) curves were constructed to assess the value of the three
      anthropometric measurements as a screening measure for total adiposity.
      Sensitivity and specificity were calculated at several percentile cut-offs for
      BMI, triceps skinfold and waist circumference. The areas under the ROC curves
      were also calculated, and were 0.86 for BMI, 0.90 for triceps skinfold and 0.88
      for waist circumference. The point on the ROC curve closest to 1 corresponded to
      the 70th percentile for BMI, to the 75th percentile for triceps skinfold, and to
      the 70th percentile for waist circumference. CONCLUSION: BMI, triceps skinfold
      and waist circumference predicted total fat content well in male children and
      adolescents.

PMID- 11332929
TI  - Anticholinergic treatment improves glycaemic control in adolescent girls with
      insulin-dependent diabetes mellitus.
AB  - Metabolic control often deteriorates during puberty in girls with insulin
      dependent diabetes. It is well accepted that there is an abnormality in the
      growth hormone (GH)-insulin-like growth factor-I (lGF-I) axis in these girls,
      resulting in reduced IGF-I levels and elevated GH. As GH antagonizes insulin,
      attempts have previously been made to reduce excess GH secretion through
      anticholinergic treatment. However, most of these studies have been performed on
      adult patients. The aim of the present study was to evaluate the effects of 12 wk
      of oral anticholinergic treatment with Pirenzepine, 100 mg twice daily, in 16
      adolescent girls with diabetes. Serum samples of IGF-I, glycated haemoglobin and
      fasting IGF-binding protein 1 were analysed at initiation and after 3, 8 and 12
      wk of Pirenzepine therapy. Nocturnal urinary GH excretion was also examined.
      Glycated haemoglobin declined significantly after 3 wk of Pirenzepine therapy
      (9.8 +/- 0.18 vs 9.2 +/- 0.17; p < 0.001) and was still improved at the end of
      the study. Unexpectedly, nocturnal urinary GH excretion did not change. Serum IGF
      I continuously increased during the study, while IGF-binding protein 1 levels
      were not significantly altered. CONCLUSION: Anticholinergic treatment with
      Pirenzepine improves glycaemic control in adolescent girls with diabetes.
      Although nocturnal urinary GH excretion was unchanged there may still be changes
      in pituitary GH secretion to explain the improvement. Effects of Pirenzepine on
      gastrointestinal motility can represent other possible mechanisms behind the
      improved metabolic control.

PMID- 11332930
TI  - Current diagnosis, management and morbidity in paediatric inflammatory bowel
      disease.
AB  - In the 1970s several reports highlighted the long delay in diagnosis often
      experienced by children with Crohn's disease. In recent years this disorder has
      attracted much publicity, and many believe that the incidence has increased
      substantially. The aim of this investigation was to determine whether heightened
      awareness had shortened the interval to diagnosis, improved clinical management
      and reduced morbidity. A retrospective study was therefore carried out on 112
      children with inflammatory bowel disease (64 Crohn's disease, 41 ulcerative
      colitis, 7 indeterminate colitis) referred to a paediatric gastroenterology
      department in the UK between 1994 and 1998. In Crohn's disease the median
      interval to diagnosis was 47 wk (maximum 7 y). In those without diarrhoea this
      was longer (66 vs 28 wk; p = 0.005). In ulcerative colitis the median interval
      was 20 wk (maximum 3 y). Even in severe colitis the median interval was 5.5 wk
      (range 3-9 wk) and 4 required urgent colectomy soon after referral. Many with
      unrecognized Crohn's disease had undergone inappropriate treatments, such as
      growth hormone or psychiatric therapy. Nineteen (17%) had undergone endoscopic
      investigations in adult units prior to referral. Malnutrition was equally common
      in Crohn's disease and ulcerative colitis (11%). Short stature was present in 19%
      with Crohn's disease, and 5% with ulcerative colitis, and was severe in 8% with
      Crohn's disease. There was a significant correlation between symptom duration and
      the degree of growth impairment present (r(s) = -0.4; p = 0.004). CONCLUSION:
      This study suggests that late diagnosis and inappropriate investigation and
      management are still significant problems.

PMID- 11332931
TI  - Rare alpha-1-antitrypsin phenotypes and liver-test abnormalities during infancy.
AB  - Over 14 y of neonatal screening 71,675 dried blood samples were examined for the
      alpha-1-antitrypsin (alpha1-AT) alleles by isoelectric focusing in the Province
      of Bozen, Northern Italy. In infants carrying abnormal phenotypes the liver
      enzymes alanine aminotransferase and gamma-glutamyltransferase were determined at
      2, 5 and 12 mo of age. In 17 neonates the PiMV phenotype was found, in 11 PiMF,
      in 11 PiMP, in 5 PiMN, in 3 PiMR, in 3 PiFZ, in 2 PiPZ and in 1 the PiMG
      phenotype was found. Two infants,1 carrying the PiMV and 1 the PiFZ phenotype
      showed at the age of 2 and 5 mo, respectively, elevated values of the liver
      enzyme S-ALAT[CE1]. Only the PiFZ and PiPZ carriers displayed low enough levels
      of alpha1-AT of 0.78 and 0.85 g l(-1) respectively, to be at moderately increased
      risk of pulmonary emphysema. Their early detection through the screening should
      discourage them from dangerous smoking habits. CONCLUSION: Only a neonatal
      screening based on phenotyping can detect these rare carriers early in life.

PMID- 11332932
TI  - Meconium passage in extremely low birthweight infants and its relation to very
      early enteral nutrition.
AB  - The aim of this study was to evaluate the correlation between the timing of the
      first and last meconium and feeding tolerance in the very early enteral nutrition
      of extremely low birthweight (ELBW) infants. Forty-one ELBW infants were fed
      following a standardized protocol (day 3-14). At 48 h of age bolus gavage feeding
      with milk was started (12 ml kg(-1) d(-1) increments, 12 meals per day). Gastric
      residuals up to 2 ml or up to 3 ml were tolerated in infants with a birthweight
      of < or = 750 g or > 750 g, respectively. No enemas or laxatives were given
      during the study. The impact of the time until the passage of the first (M-1) and
      last (M-last) meconium on the feeding volume on day 14 (V14) was evaluated by
      linear regression analysis. Data are presented as median (range). M-1 was 31 h
      (0.5-77 h), M-last was 6 d (1.4-22 d) and V14 was 99 (0-156) ml kg(-1). V14
      increased with decreasing M-last (p < 0.001) but there was no correlation between
      V14 and M-1. V14 was 112 (0-156) ml kg(-1) if M-last was shorter than 6 d and 37
      (0-147) ml kg(-1) if M-last was longer than 6 d. CONCLUSION: Rapid meconium
      evacuation appeared to be a key factor for the feeding tolerance of ELBW infants
      during the first 14 d of life. Further studies needed to investigate whether
      meconium passage can be accelerated and whether acceleration of the meconium
      passage will improve the early feeding tolerance in ELBWW infants.

PMID- 11332933
TI  - Phospholipase A2 is present in meconium and inhibits the activity of pulmonary
      surfactant: an in vitro study.
AB  - Atelectasis, a major contributor to pulmonary dysfunction in meconium aspiration
      syndrome (MAS), is produced by bronchiolar obstruction and surfactant
      inactivation. It has been shown that substances in meconium, e.g. fatty acids,
      inhibit surfactant activity. However, the role of the enzyme phospholipase A2
      (PLA2), which hydrolyses surfactant in adult respiratory distress syndrome
      (ARDS), has not yet been studied. Our objective was to investigate whether PLA2
      is present in meconium and inhibits pulmonary surfactant activity in vitro.
      Therefore, the presence of PLA2 activity in meconium, collected from 10 newborns,
      was measured by the formation of lysophosphatidylcholine after incubation of
      meconium with radioactively labelled dipalmitoylphosphatidylcholine. Meconium was
      fractionated by Sephadex G-100 column chromatography and the fractions were
      assayed for PLA2 activity. Also, their effect on the surface tension of
      surfactant (Curosurf) was measured using a pulsating bubble surfactometer (PBS).
      PLA2 activity was present in all meconium samples. Addition of meconium to
      surfactant significantly increased surface tension (mean +/- SD: 1.7 +/- 1.6 mN/m
      to 24.3 +/- 6.7 mN/m, p = 0.0001) and only the addition of the PLA2 containing
      fraction from meconium to surfactant also significantly increased surface tension
      (mean 1.7 +/- 1.6 mN/m to 19.0 +/- 3.58 mN/m, p < 0.0001). CONCLUSION: PLA2 is
      present in meconium and inhibits the activity of pulmonary surfactant in vitro.
      Therefore, PLA2 in meconium may contribute to surfactant inactivation and
      alveolar atelectasis in MAS.

PMID- 11332934
TI  - Parental reported apnoea, admissions to hospital and sudden infant death
      syndrome.
AB  - Three studies were undertaken: (i) a nation-wide case-control study for sudden
      infant death syndrome (SIDS), with 393 cases and 1592 controls, examined the
      association between parental reported apnoea and SIDS; (ii) a case-cohort study,
      with 84 cases of parental reported apnoea and 1502 controls, aimed to identify
      risk factors for apnoea; and (ii) national hospital admission data for ALTE and
      national SIDS mortality data were compared for the years 1986 to 1994. Parental
      reported apnoea was associated with a significant increased risk of SIDS
      [adjusted odds ratio (OR) 1.86; 95% confidence interval (CI) 1.12, 3.09]. The
      population attributable risk was 8%. There was a significant increased risk for
      parental reported apnoea in infants who did not die after adjustment for
      potential confounders with maternal smokers, short gestation and admission to the
      neonatal unit. There was no association with prone sleeping position, co-sleeping
      and bottle feeding. The mean annual admission rate for ALTE was 9.4/1000 live
      births. This did not change significantly over the study period (1986-1994). In
      contrast, the SIDS mortality rate decreased from over 4/1000 to 2.1/1000.
      Admission rates were higher for Maori infants and boys. CONCLUSION: It may be
      concluded that the relationship between parental reported apnoea and SIDS is
      tenuous.

PMID- 11332935
TI  - Maternal employment and the initiation of breastfeeding.
AB  - This study examines whether planning to be employed postpartum has an effect on
      initiation of breastfeeding. Data were collected from questionnaires completed by
      mothers who were subjects in the prospective, population-based, Avon Longitudinal
      Study of Pregnancy and Childhood. The mothers of 10,530 full-term singleton
      infants gave information during pregnancy on their postpartum employment plans
      and their initial infant feeding methods. Information was also given by 7642 of
      these mothers on the timing of their postpartum employment plans. Adjusted
      logistic regression was performed to identify associations between (a) "any"
      plans to work postpartum and the initiation of breastfeeding, and (b) the timing
      of the commencement of work postpartum, and the initiation of breastfeeding. A
      total of 8316 (79%) of the women initiated breastfeeding. The decision to
      breastfeed was not associated with "any" plans to work postpartum. However, women
      who planned to commence work prior to 6 wk postpartum were significantly less
      likely to initiate breastfeeding compared with those not intending to work
      postpartum. Older, more highly educated women, women who had or were planning to
      attend childbirth classes, women who were breastfed as infants, women who did not
      smoke and women who were giving birth to their first child were significantly
      more likely to initiate breastfeeding. CONCLUSION: Planning to return to
      employment prior to 6 wk postpartum reduces the likelihood of initiating
      breastfeeding. As increasing numbers of mothers are returning to work shortly
      after the birth of their child, this finding could have implications for
      maintaining the current level of breastfeeding.

PMID- 11332937
TI  - Sexual behaviour in Swedish preschool children, as observed by their parents.
AB  - Issues of what constitutes normal and healthy childhood sexual behaviour have
      acquired new implications in the light of child sexual abuse. Increased knowledge
      in this area is therefore of vital importance and studies in different countries
      are needed. In the present study parents of 231 children aged 3-6 y were asked to
      answer questionnaires about their child's behaviour at home. The questionnaire
      consisted of four sections: demographic data, a general behaviour checklist, a
      sexual behaviour inventory, and attitudinal questions to the parents. The results
      showed that children in Sweden exhibit a wide range of sexual behaviour, most of
      them developmentally related. Some behaviour appeared to be very rare in a
      normative sample of preschool children and included behaviours usually referred
      to as sexualized and problematic. Reports on sexual behaviour in the children
      were also related to general behaviour reports, the parent's socioeconomic level,
      parental attitudes towards child sexuality and the openness of family habits.
      CONCLUSION: There is a need for further national studies in different settings,
      to help create a better understanding of what constitutes both normative and
      deviant sexual behaviour in children.

PMID- 11332936
TI  - Sociodemographic differences in patterns of sedentary and physically active
      behavior in older children and adolescents.
AB  - Numerous studies have found that involvement in moderate-intensity and strenuous
      activity has positive effects on health. This study considered the prevalence of
      different aspects of physical activity and sedentary behavior in 11-16-y-olds
      based on a representative national survey of 3270 Icelandic primary
      schoolchildren (91% response rate). All-day sedentary behavior was extremely rare
      (< 1%), and the vast majority (91%) were physically active (> or = 3 times per
      week) during school or leisure time, thanks largely to school physical education.
      Only 39% were physically active (> or = 3 times per week) during leisure time,
      and only 29% engaged in regular (> or = 3 times per week) leisure time strenuous
      exercise. Girls were more sedentary, less leisure time physically active, and
      less involved in leisure time strenuous exercise. Sedentary behavior increased
      and physically active behavior decreased with age, especially after early
      adolescence. However, there were no age differences in strenuous leisure time
      exercise. Upper-class students were less sedentary and more physically active
      during leisure time than working-class students. Finally, rural students were
      more sedentary during leisure time, and less physically active than students from
      urban areas. An interaction was found between age and residence when predicting
      leisure time physical activity, indicating that the inverse age-activity
      relationship in urban areas is partly reversed in rural areas. CONCLUSION:
      Compulsory school physical education frequently failed to translate into
      voluntary physical involvement. Sociodemographic differences in physical activity
      were greater during leisure time, than during school and leisure time combined.

PMID- 11332938
TI  - Comparison of airway pressure and airflow triggering systems using a single type
      of neonatal ventilator.
AB  - The performances of two triggering systems using a single neonatal ventilator
      type (SLE) were compared. Eight infants, gestational age 27-30 wk, were each
      recorded during two 1-h periods of patient-triggered ventilation (PTVs), one with
      airway pressure and one with airflow triggering. The airflow trigger had a
      shorter trigger delay (p < 0.02), higher sensitivity (p < 0.02) and lower
      asynchrony rate (p < 0.02). CONCLUSION: In immature infants with mild respiratory
      distress syndrome using the SLE ventilator with inflation times of 0.3 to 0.36
      sec, airflow triggering is more appropriate than airway pressure triggering.

PMID- 11332939
TI  - Reactive thrombocytosis in children with upper urinary tract infections.
AB  - The relationship between reactive thrombocytosis and the level of urinary tract
      infections was studied in 48 children. Platelets were counted before, during and
      after treatment. Reactive thrombocytosis was noticed in 74% of children with
      upper and in 14% with lower urinary tract infections. A significant rise in the
      platelet count presented in another five children (15%) with upper urinary tract
      infections. CONCLUSION: Reactive thrombocytosis was found almost exclusively in
      the renal parenchymal infections, usually during the recovery phase.

PMID- 11332940
TI  - High proportions of n-6 polyunsaturated fatty acids in mature milk of mothers in
      Ouagadougou, Burkina Faso.
AB  - Milk from 101 mothers living in Ouagadougou (Burkina Faso) showed a mean lipid
      content of 33.42 g/l and a fatty acid composition strongly related to the
      mothers' dietary habits: high proportions of linoleic acid (19.80%), n-6 long
      chain polyunsaturated fatty acids (1.90%), and 8:0-14:0 saturated fatty acids
      (26.94%). CONCLUSION: The proportions of alpha-linolenic acid (0.45%) and n-3
      long-chain polyunsaturated fatty acids (0.44%) were low. The 18:2/18:3 and n-6/n
      3 long-chain polyunsaturated fatty acids ratios (53:1 and 5:1, respectively) were
      well above recommendations.

PMID- 11332941
TI  - Incarcerated inguinal hernia in premature babies--a report of two cases.
AB  - We highlight the morbidity of incarcerated inguinal hernia in very low
      birthweight (VLBW) infants by presenting a report of two cases. Our aim is to
      raise the question of the optimal timing of surgery when this common problem
      presents on the neonatal unit. In each of our cases the hernia was diagnosed but
      surgery was delayed, as per normal policy on the unit, pending growth of the baby
      and improvement in respiratory status. Both babies suffered significant morbidity
      when the hernias subsequently became acutely incarcerated. CONCLUSION: In
      conclusion, we question whether the widespread practice of delayed surgery for
      inguinal hernia in VLBW infants should be reconsidered.

PMID- 11332942
TI  - Fertility in Prader-Willi syndrome: a case report with Angelman syndrome in the
      offspring.
AB  - We report on a 32-y-old woman with Prader-Willi syndrome (PWS) and her daughter
      with Angelman syndrome (AS). PWS in the mother was confirmed as due to a deletion
      of 15q11-q13, and molecular analysis in the neonate indicated an inherited
      maternal deletion of the same region. Features of AS in early infancy, such as
      jerky movements, feeding problems and poor sleep, were observed. At 5 mo of age,
      a triphasic high voltage EEG pattern was reported. CONCLUSIONS: This case
      confirms the non-Mendelian inheritance of PWS and AS and, in addition to previous
      reports, provides evidence of fertility in PWS women. We recommend the provision
      of information regarding fertility in females with PWS to parents, guardians and
      individuals with PWS, and frequent EEG monitoring for early AS diagnosis. Given
      the different genetic aetiologies for PWS and AS, cytogenetic and molecular
      genetic analysis is strongly indicated for counselling and risk estimation.

PMID- 11332943
TI  - Long chain polyunsaturated fatty acids (LC-PUFA) and perinatal development.
AB  - This paper reports on the conclusions of a workshop on the role of long chain
      polyunsaturated fatty acids (LC-PUFA) in maternal and child health. The attending
      investigators involved in the majority of randomized trials examining LC-PUFA
      status and functional outcomes summarize the current knowledge in the field and
      make recommendations for dietary practice. Only studies published in full or in
      abstract form were used as our working knowledge base. CONCLUSIONS: For healthy
      infants we recommend and strongly support breastfeeding as the preferred method
      of feeding, which supplies preformed LC-PUFA. Infant formulas for term infants
      should contain at least 0.2% of total fatty acids as docosahexaenoic acid (DHA)
      and 0.35% as arachidonic acid (AA). Since preterm infants are born with much less
      total body DHA and AA, we suggest that preterm infant formulas should include at
      least 0.35% DHA and 0.4% AA. Higher levels might confer additional benefits and
      should be further investigated because optimal dietary intakes for term and
      preterm infants remain to be defined. For pregnant and lactating women we
      consider it premature to recommend specific LC-PUFA intakes. However, it seems
      prudent for pregnant and lactating women to include some food sources of DHA in
      their diet in view of their assumed increase in LC-PUFA demand and the
      relationship between maternal and foetal DHA status.

PMID- 11332944
TI  - Ibuprofen-lysine for closure of patent ductus arteriosus.

PMID- 11332945
TI  - Influenza vaccination in HIV-infected children.

PMID- 11332946
TI  - Dietary intervention in the first four years prevents abnormal weight gain but
      negatively affects height development in Prader-Willi syndrome.

PMID- 11332947
TI  - Caroli's syndrome and horseshoe kidney: a case report.

PMID- 11332948
TI  - Recent advances in the management and prophylaxis of respiratory syncytial virus
      infection.
AB  - Respiratory syncytial virus (RSV) infection is an important cause of morbidity,
      particularly in prematurely born infants who have had chronic lung disease.
      Current therapy is essentially supportive. Overall, the results of randomized
      trials do not support the use of bronchodilators, corticosteroids or Ribavirin.
      Nitric oxide and exogenous surfactant may improve the respiratory status of those
      infants who require ventilatory support. Nosocomial infection can be reduced by
      appropriate handwashing. There is no safe and effective vaccine for use in
      infants. Immunoprophylaxis reduces hospitalization and requirement for intensive
      care. Palivizumab, a humanized monoclonal antibody, is preferred to RSV immune
      globulin as the immunoprophylactic agent. Immunoprophylaxis should be reserved
      for infants at highest risk of severe respiratory syncytial virus infection, if
      this strategy is to be used most cost-effectively.

PMID- 11332949
TI  - Uncertainties about the use of inhaled nitric oxide in preterm infants.
AB  - Respiratory failure in the premature neonate is frequently complicated by
      pulmonary hypertension. When conventional therapies including administration of
      exogenous surfactant, conventional mechanical ventilation or high-frequency
      oscillatory ventilation using an appropriate high-volume strategy have failed,
      one should assess the pulmonary circulation status with colour-coded Doppler
      echocardiography. There is now considerable evidence that the regulation of
      foetal and postnatal pulmonary circulation occurs via nitric oxide (NO), and that
      persistent pulmonary hypertension of the neonate may be related to a relative
      deficiency in NO release. Low-dose (10-20 ppm), short-duration (1-2 d) inhaled NO
      has generally been shown to improve the oxygenation and relieve pulmonary
      hypertension in premature neonates with severely hypoxaemic respiratory failure.
      Whether this therapy (eventually prolonged >1-3 wk?) would improve survival and
      lessen morbidity (e.g. intracranial haemorrhage and chronic lung disease) remains
      to be proven by appropriately designed controlled trials. Until these issues can
      be clarified, NO therapy for premature neonates should be still considered as an
      experimental drug, and its use restricted to clinical studies.

PMID- 11332950
TI  - Trophic feeding of the preterm infant.
AB  - Trophic feeding is the practice of feeding minute volumes of enteral feeds in
      order to stimulate the development of the immature gastrointestinal tract of the
      preterm infant This paper reviews the randomized controlled studies that have
      examined the physiological and clinical responses to trophic feeding of the
      preterm infant. Trophic feeding alters gastrointestinal disaccharidase activity,
      hormone release, blood flow, motility and microbial flora. Clinical benefits
      appear to include improved milk tolerance, greater postnatal growth, reduced
      systemic sepsis and shorter hospital stay. There is currently no evidence of any
      adverse effects following trophic feeding.

PMID- 11332951
TI  - Patient-triggered ventilation in premature neonates.
AB  - Observed short-term benefits of patient-triggered ventilation include
      improvements in oxygenation and carbon dioxide elimination, reduced cerebral
      blood flow variability, more rapid weaning from ventilation and reduced
      adrenaline levels. The three multicentre randomized controlled trials in which
      longer term outcomes were investigated failed to demonstrate any consistent
      reductions in rates of pneumothorax, chronic lung disease, cranial ultrasound
      changes, duration of ventilation or mortality. Two of these studies were
      conducted wholly or predominantly using the SLE 2000 ventilator, with the Drager
      Babylog 8000 used in a minority of infants. The results therefore reflect only
      the performance of these ventilators, with the ventilation techniques used. As
      the degree to which synchrony was achieved was not measured in any of these
      studies, they provide no evidence for a lack of benefit from achieving
      synchronous ventilation. It is possible that the findings were influenced by the
      use of drugs, especially morphine and theophylline. In one study the pneumothorax
      rate was significantly lower in infants recruited within 3 mo of the first
      patient enrolled at that centre, and was seen with both modes of ventilation.
      This suggests that staff education in ventilation techniques may be important in
      reducing pneumothorax rates.

PMID- 11332952
TI  - Animal-derived or synthetic surfactant for the treatment of neonatal respiratory
      distress syndrome: a review.
AB  - Animal-derived surfactants containing SP-B and SP-C are more effective in vitro
      and in animal models than their synthetic counterparts, but are not as effective
      as unmodified, naturally occurring surfactant. In clinical trials involving
      newborn babies with respiratory distress syndrome (RDS) these short-term
      differences are reflected as improvements in gas exchange and lung function.
      Treatment with animal-derived surfactants results in fewer air leaks and lower
      neonatal mortality. The evidence is now strong enough to recommend routine use of
      animal-derived surfactants in very preterm infants with RDS. The newer generation
      of synthetic surfactants may be important in the future as they have the
      advantages of currently available animal products with the addition of better
      resistance to inactivation.

PMID- 11332953
TI  - Advances in the treatment of the meconium aspiration syndrome.
AB  - Meconium aspiration syndrome (MAS) is a common cause of respiratory distress in
      neonates. In many affected children, the complex nature of meconium aspiration
      syndrome contributes to the apparent lack of response to standard therapies. Over
      the past decade, several new therapies have been suggested to be more effective
      than "conventional" management in treating meconium aspiration syndrome. These
      include: anti-inflammatory drugs, medications to counter the effect of
      prostaglandin-related compounds, high-frequency ventilation, exogenous
      surfactant, inhaled nitric oxide and liquid ventilation. There are, however,
      scant evidence-based data to justify routine use of any of those therapies.
      Additional prospective, well-controlled, randomized trials of diverse therapies
      are needed to elucidate the optimum management of MAS.

PMID- 11332954
TI  - Is oxidative stress involved in the aetiology of pre-eclampsia?
AB  - Pre-eclampsia is one of the major indications for elective premature delivery.
      Several lines of evidence suggest that pre-eclampsia is associated with a state
      of oxidative stress, offering hope of prevention by antioxidant supplementation.
      It was recently shown by the present authors that supplementation with vitamin C
      and E from early in pregnancy leads to a reduction in the incidence of the
      disease in "high-risk" women.

PMID- 11332955
TI  - Twins and cerebral palsy.
AB  - In a national follow-up study of twin births, monozygous compared with dizygous
      twins were at significantly increased for both to die in utero, one to die in
      utero and the co-twin to die in infancy, or both to be livebirths but both die in
      infancy. The prevalence of cerebral palsy among survivors of a co-twin fetal
      death was 80.2 and other cerebral impairment was 107.0 per 1000. Many apparently
      singleton cases of cerebral palsy and impairment may be due to fetal death of a
      twin that has not been recognized or has been recognized but not registered.

PMID- 11332956
TI  - Efficacy of school scoliosis screening.

PMID- 11332957
TI  - Conservative treatment of clubfoot.

PMID- 11332958
TI  - Comparing world health-care systems: does quality translate?

PMID- 11332959
TI  - Radiologic case study. Disk prolapse.

PMID- 11332960
TI  - Midlateral incision for trigger thumb release.

PMID- 11332961
TI  - The role of hip arthroscopy in the evaluation of avascular necrosis.
AB  - This prospective study evaluated the correlation between plain radiographs,
      magnetic resonance imaging (MRI), and diagnostic arthroscopy in the staging of
      avascular necrosis of the femoral head. Fifty-two hips in 46 patients were
      prospectively staged using radiographic and MRI staging systems. Patients
      subsequently underwent hip arthroscopy to visualize the articular surface prior
      to considering salvage of the femoral head and debride delaminated osteochondral
      fragments. Weighted Kappa analysis revealed only moderate correlation between MRI
      and plain radiographs (K=.11), MRI and arthroscopy (K=.21), and plain radiographs
      and arthroscopy (K=.19). Six (46%) of 13 patients with a radiographically
      apparent subchondral fracture demonstrated collapse of the articular surface at
      arthroscopy. Four (24%) of 17 hips with >2 mm of collapse of the femoral head on
      plain radiographs demonstrated fragmentation of the osteochondral surface of the
      femoral head at arthroscopy. In 5 patients with flattening of the femoral head, 3
      patients had delamination of both the femoral and acetabular surfaces. In regard
      to labral pathology, 5 of 22 post-collapse hips also had large bucket handle
      tears of the labrum. Arthroscopy of the hip revealed osteochondral degeneration
      that was not detected by plain radiographs or MRI in 36% of post-collapse femoral
      heads.

PMID- 11332962
TI  - Assessment of the endoscopic semitendinosus/gracilis autograft procedure with
      interference screw fixation for reconstruction of the anterior cruciate ligament.
AB  - The semitendinosus/gracilis autograft procedure with interference screw fixation
      was evaluated for clinical effectiveness of anterior cruciate ligament (ACL)
      reconstruction. Thirty patients underwent the procedure and were evaluated an
      average of 15 months postoperatively. Results revealed 22 (73%) patients had a
      standard knee evaluation form score of normal or nearly normal, and 24 (80%)
      patients returned to strenuous or moderate activity levels. Average Lysholm
      outcome score was 89, and bilateral KT-2000 differences were <3 mm at follow-up.
      Functional knee test symmetry index percentage outcome for the one-legged hop
      test was 92.6% for distance and 98% for time. Length of time (i.e., < or =90 days
      or > or =91 days) between injury and surgery was independent of outcome. These
      findings indicate the semitendinosus/gracilis autograft is a viable procedure for
      reconstruction of the ACL-deficient knee.

PMID- 11332963
TI  - Impending or completed pathologic femur fractures treated with intramedullary hip
      screws.
AB  - This study examined the use of the long intramedullary hip screw in 13
      consecutive patients with metastatic disease of the femur with impending or
      completed fractures. There were 6 impending and 7 completed fractures. Eleven of
      13 patients had unreamed rods placed with an average operative time of 100
      minutes and blood loss of 280 cc. Eleven of 12 patients who were able to ambulate
      preoperatively regained that status postoperatively. Postoperative complications
      included death (1), myocardial infarction (1), and urinary tract infection (2).
      These results indicate the long intramedullary hip screw is a safe and effective
      surgical device for treating metastatic disease of the femur.

PMID- 11332964
TI  - Operative treatment with radial shortening in Kienbock's disease.
AB  - Eighty-eight patients underwent radial shortening for Kienbock's disease.
      Prerequisites for surgery were radiographic studies positive for Kienbock's
      disease without evidence of radiocarpal arthritis and wrist pain unrelieved by
      conservative management. Thirty-nine patients were evaluated by subjective
      questionnaire at a mean postoperative follow-up of 86 months (range: 24-188
      months). Following surgery, a significant decrease was noted in pain severity,
      frequency, and duration. Functional status improved postoperatively, with the
      most significant gains noted in the following activities: opening jars, opening
      car doors, carrying bags, and shoveling. Only 3 of 34 patients employed outside
      the home were unable to return to their original occupations due to their wrist
      problems. Seventy-six patients were evaluated by physical examination at a mean
      postoperative follow-up of 31 months (range: 3-87 months). Objective evaluation
      by physical examination revealed a significant improvement in wrist motion and
      grip strength. Seventy-seven patients underwent radiographic evaluation at a mean
      postoperative follow-up of 31 months (range: 3-180 months). A significant
      progression in Lichtman stage of Kienbock's disease was noted despite the
      favorable subjective findings and high satisfaction ratings. Thirty-six of 39
      patients stated they would undergo the surgery again. The long-term data
      demonstrate radial shortening in patients with stage II-IIIA Kienbock's disease
      provides substantial improvement over preoperative status.

PMID- 11332965
TI  - The effect of freezing and intraosseous fluid on the stiffness behavior of canine
      trabecular bone.
AB  - The effect of disrupting the intraosseous fluid compartment and freezing on the
      mechanical stiffness of trabecular bone in intact canine femoral head specimens
      was investigated. Twenty-four skeletally mature dogs were divided into two
      groups. Twelve paired fresh femora were tested and 12 paired femora were tested
      after freezing at -20 degrees C. The intact femoral head specimens were subjected
      to a load of physiologic magnitude, and then the stiffness of the underlying
      trabecular bone was determined in intact femora, in drilled femora with a
      disrupted intraosseous fluid compartment, and subsequently after refilling the
      compartment with fluid. Drilling of the femoral head and disrupting its bony
      fluid compartment resulted in a 40% decrease in stiffness (P<.001). This effect
      was seen only with fresh specimens and not frozen specimens. Refilling the bony
      compartment with fluid restored the stiffness of the fresh femoral head. These
      results demonstrate the mechanical properties of trabecular bone in canine
      femoral head specimens in vitro are affected by intraosseous fluid and freezing.
      Removal of the intraosseous fluid decreases the mechanical stiffness of canine
      trabecular bone, and freezing the specimens appears to alter the intraosseous
      fluid compartment behavior. It is necessary to gain a better understanding of the
      dynamic mechanical properties of intact bone to improve the existing analytical
      and experimental mechanical bone models. The effect of intraosseous fluid and
      freezing should be considered in these models.

PMID- 11332966
TI  - Comparison of metal versus absorbable implants in tension-band wiring: a
      preliminary study.
AB  - The strength of tension-band wiring using bioabsorbable materials versus metal
      implants was assessed with a rabbit knee fusion model. Ten rabbit knees were
      osteotomized and rigidly fixed using a tension-band technique: five with metal
      implants (2 pins and 24-gauge wire) and five with absorbable implants (2-mm pins
      [Bionx, Blue Bell, Pa] and 1 Maxon [Davis and Geck, Danbury, Conn]).
      Biomechanical testing of the fixation strength was completed using a
      servohydraulic mechanical testing machine and a specifically designed four-point
      bending jig. The parameters assessed were maximal load, relative stiffness,
      displacement, and bending moment of the constructs. Results of the biomechanical
      testing showed no statistical difference between the constructs on any of the
      parameters assessed.

PMID- 11332967
TI  - Unusual penetrating hand injuries due to underwater fishing harpoons.

PMID- 11332968
TI  - Femoral bifurcation associated with tibial hemimelia.

PMID- 11332969
TI  - Tuberculous compartment syndrome of the forearm.

PMID- 11332970
TI  - Proximal tibiofibular arthritis: an unusual cause of lateral knee pain.

PMID- 11332971
TI  - The role of injectable corticosteroids in orthopedics.

PMID- 11332972
TI  - Metabolic studies in older mentally retarded patients: significance of metabolic
      testing and correlation with the clinical phenotype.
AB  - In 471 adult mentally retarded adult patients (mean age 46 years; 92.6% males)
      living in an institution for the mentally retarded, a clinical examination,
      cytogenetic and molecular studies were done. 306 patients were screened for
      metabolic disorders. In 7 additional patients a metabolic disorder
      (phenylketonuria (n = 5), mucopolysaccharidosis type III (Sanfilippo syndrome,
      type A) (n = 1) and mucopolysaccharidosis type VII (Sly syndrome) (n = 1)) was
      diagnosed in the past. The abnormal metabolic findings in this group of 313
      patients were classified in three categories and the clinical findings are
      reported: 1. metabolic disorders as the cause of mental retardation (MR), 2.
      metabolic disorders not explaining the MR, and 3. metabolic abnormalities of
      unknown significance. The first two groups included 16 patients, i.e. 26.2% of
      the group of monogenic disorders and 3.4% of the total population:
      phenylketonuria (PKU) (n = 5), S-sulfocysteinuria (n = 3), mucopolysaccharidosis
      type III (Sanfilippo syndrome, type A) (n = 1) and Gm1-gangliosidosis type 3 (n =
      1) (first group), and mucopolysaccharidosis type VII (Sly syndrome) (n = 1),
      Niemann-Pick syndrome, type B (n = 1), cystinuria (n = 1) and hyperprolinemia
      type 1 (n = 3) (second group). The third group included patients with
      citrullinemia (n = 2), methionine sulphoxide reductase deficiency (n = 1),
      ornithinemia (n = 1), glycinuria (n = 20), neuraminaciduria (n = 8), uraciluria
      (n = 6) and diabetes mellitus (n = 2). Screening for Congenital Disorders of
      Glycosylation (CDG) in 144 patients and for Smith-Lemli-Opitz syndrome (SLO) in a
      selected group of 6 patients was normal. Of the total group of 306 patients
      screened for inborn errors of metabolism, only 5 (1.6%) were found with a true
      metabolic disorder. These 5 patients presented clinical symptoms,
      neurodegenerative or behavioural problems, indicating further metabolic
      screening. The present study illustrates that a selected group of patients with
      mental retardation of unknown origin are candidates for metabolic screening,
      especially if aberrant behaviour, neurodegenerative problems or dysmorphic
      features are present.

PMID- 11332973
TI  - Micro-ablepharon of the upper eyelids and vaginal atresia.

PMID- 11332974
TI  - MCA/MR syndrome with occipital scalp defect and valvular pulmonary stenosis: a
      cryptic 7pter duplication/18qter deficiency.

PMID- 11332975
TI  - Sex chromosome pentasomy (49, XXXXY) presenting with generalized oedema and
      hypogenitalism at 12 weeks.

PMID- 11332976
TI  - Phenotypic variability of Cat-Eye syndrome.
AB  - Cat-Eye syndrome (CES) is a disorder with a variable pattern of multiple
      congenital anomalies of which coloboma of the iris and anal atresia are the best
      known. CES is cytogenetically characterised by the presence of an extra
      bisatellited marker chromosome, which represents an inverted dicentric
      duplication of a part of chromosome 22 (inv dup(22)). We report on three CES
      patients who carry an inv dup(22) diagnosed with FISH studies. They show
      remarkable phenotypic variability. The cause of this variability is unknown.
      Furthermore, we review clinical features of 71 reported patients. Only 41% of the
      CES-patients have the combination of iris coloboma, anal anomalies and pre
      auricular anomalies. Therefore, almost 60% of the CES-patients are hard to
      recognize by their phenotype alone. Mild to moderate mental retardation was found
      in 32% (16/50) of the cases. Mental retardation occurs more frequently in male
      CES-patients. There is no apparent phenotypic difference between mentally
      retarded and mentally normal CES-patients.

PMID- 11332977
TI  - Wolf-Hirschhorn (4P-) syndrome in adults.
AB  - Wolf-Hirschhorn syndrome (WHS) or 4p-deletion syndrome has been extensively
      described in children. Knowledge on adult WHS patients is still limited due to
      the small number of published cases. We present 4 adults and review the
      literature. The phenotype of adult WHS is in general similar to that of childhood
      WHS. Growth retardation, microcephaly and mental retardation are the rule in both
      adults and children. Facial dysmorphism also remains similar. The main difference
      lies in the absence of serious internal (cardiac) abnormalities in adult WHS.
      Mental retardation ranges from moderate to severe. The nosological overlap
      between WHS and Pitt-Rogers-Danks syndrome (PRDS) is discussed. More extensive
      data on adult WHS are needed for appropriate counselling of families with
      affected young children.

PMID- 11332978
TI  - Fuhrmann syndrome associated with cortical dysplasia.
AB  - We describe a male newborn with bilateral angle bowing of femora, absent fibulae,
      aplasia of the fingernails, hypoplastic toenails, malformed thumbs, hypospadias,
      inguinal hernia and cortical dysplasia in a consanguineous Turkish Family. The
      MCA syndrome in the present patient is similar to these reported in 3 affected
      sibling by Fuhrmann et al.

PMID- 11332979
TI  - Attitudes of young patients with Parkinson's disease towards possible
      presymptomatic and prenatal genetic testing.
AB  - OBJECTIVE: To evaluate the opinions and attitudes of young patients with
      Parkinson's disease (PD) towards possible presymptomatic and prenatal genetic
      testing for their illness. BACKGROUND: With progress in understanding of the
      genetic component in the etiology of PD, presymptomatic genetic testing may
      become available in subgroups of patients. METHODS: During a survey on
      sociodemographic and risk factors 111 PD patients (mean age 45 years: mean age at
      PD onset 36 years) were given a questionnaire with six items about possible
      presymptomatic and prenatal genetic testing. RESULTS: Fifty-seven patients (5196)
      had knowledge about presymptomatic and prenatal testing. Eighty patients (72%)
      would take a presymptomatic test, if they had an autosomal dominant form of PD
      and if the test were available. The most Important reasons given for taking the
      test were planning of partnership (40%) and family (48%). When being identified
      as a carrier of a presumed "Parkinson gene", 78 patients (70%) would decide not
      to have children. Sixty-three patients (57%) would choose to have prenatal
      testing. Attitudes were largely independent of sociodemographic and disease
      variables. CONCLUSIONS: When addressed as hypothetical persons at genetic risk,
      young patients with PD support possible presymptomatic genetic testing and, to a
      lesser extent, prenatal testing. Attitudes and reasons to participate in such
      hypothetical testing do not grossly differ from those of at-risk persons in
      established single-gene autosomal dominant disorders of late onset.

PMID- 11332980
TI  - De novo unbalanced t(11q;21q) leading to a partial monosomy 21pter-q22.2 and
      11q24-qter in a patient initially diagnosed as monosomy 21.
AB  - We describe a patient in whom full monosomy 21 was initially assumed from routine
      GTG banded karyotyping. Re-examination with chromosome painting demonstrated an
      unbalanced translocation between the long arms of chromosomes 11 and 21.
      Fluorescence in situ hybridization (FISH) and microsatellite marker analysis
      revealed partial monosomy of chromosome 21 (pter-q22.2) and 11 (q24-qter). The
      patient was prematurely born in the 31st week of gestation and expired 3 days
      after delivery. She showed multiple minor anomalies, a complex cardio-vascular
      malformation, intestinal malrotation and cerebellar hypoplasia.

PMID- 11332982
TI  - Partial distal trisomy 3p. A partial autosomal trisomy without major dysmorphic
      features.
AB  - Whereas in the great majority of autosomal duplications/deficiencies a clinically
      recognizable dysmorphic syndrome is present, distal 3p duplication is not
      associated with major dysmorphic signs. We present the clinical data and
      molecular cytogenetic findings in two non-related patients. Diagnosis was made in
      a female child at the age of 5 months because of psychomotor retardation and
      slight dysmorphism. She also presented hydronefrosis and develops no speech at
      the age of almost 4 years. Her partial trisomy is the result of an inverted
      duplication 3p22-->3pter (dup(3)(pter-->p26::p22(p26::p26-->ter)). An adult woman
      was diagnosed at the of 80 years only on the basis of mental retardation and poor
      speech development, but without evident dysmorphism. In this patient the partial
      3p trisomy is the unbalanced product of a 3p/17p translocation:
      t(3;7)(p253;p133).

PMID- 11332981
TI  - A case of symbrachydactyly with oligodactyly.
AB  - The term symbrachydactyly describes syndactyly accompanied by brachydactyly.
      Brachydactyly is seen in middle phalanges of both hands and feet and very short
      in length or absent. As for syndactyly it is a cutaneous type. It has always been
      observed unilaterally and sporadically. A familial type of this syndrome has also
      been reported. There have been many classifications of symbrachydactyly. Of
      these, Blauth classification is the most favored one. Yet these classifications
      have been inadequate to include many recently discovered other forms of
      symbrachydactyly. A three month old child was brought to the Istanbul University
      Genetic Research Center because of his abnormal hands and feet. He was the second
      child of a couple who had no kinship ties to each other. In the history of the
      family, there was no mention of any anomaly as such. There was a complete
      syndactyly involving the 3rd through the 5th fingers, partial syndactyly between
      the 2nd and 3rd, and the thumb was normal in the right hand. There was only one
      finger in the left hand. There was total syndactyly in four toes of the right
      foot with oligodactyly and absence of the big toe. The left foot had five toes
      with a complete syndactyly between the 2nd and the 3rd. Radiological observation
      indicated that the middle phalanges of both extremities were rudimentary or never
      developed. There was no osseous syndactyly. As observed in this case,
      oligodactylous type that is bilateral and involves both hands and feet together
      is very unusual. The purpose of this study is to present a rare case of this
      anomaly that requires a reassessment of symbrachydactyly and its traditional
      classifications.

PMID- 11332983
TI  - Cystic hygroma colli as the first echographic sign of the fetal akinesia
      sequence.
AB  - We report first trimester cystic hygroma colli with subsequent resolution and
      development of a fetal akinesia deformation sequence. Neuropathological
      examination of the brain showed intra- and extracellular white matter edema while
      spinal cord, peripheral nerves and muscles were normal. Hygroma colli as the
      first echographic sign of subsequent severe fetal akinesia sequence without
      muscular dystrophy as seen in the Lethal Multiple Pterygium syndrome has not been
      previously reported.

PMID- 11332984
TI  - A maternal inherited translocation t(1;22)(q11;p11) in two infertile brothers.
AB  - We report two infertile brothers presenting with azoospermia and oligozoospermia.
      Cytogenetic studies using G-banding and FISH analysis on lymphocyte cultures
      revealed an autosomal balanced reciprocal translocation t(1;22)(q11;p11) in both
      males. The same translocation was found in their mother, but not in a third
      fertile brother and maternal uncle suggesting that this translocation might
      compromise the male but not the female gametogenesis in this family.

PMID- 11332985
TI  - Intramuscular electroporation delivery of IL-12 gene for treatment of squamous
      cell carcinoma located at distant site.
AB  - Gene therapy with IL-12 has been shown to elicit potent systemic antitumor
      response in a variety of tumors. Although direct intratumoral injection is the
      most commonly used delivery route for gene therapy of solid tumors, the skeletal
      muscle has been shown to be an ideal tissue for gene delivery to produce systemic
      gene expression. We have previously demonstrated that electroporation delivery of
      a reporter gene to muscle enhances the transfection efficiency and the level of
      gene expression by two to three logs. We report here that intramuscular (i.m.)
      injection of as little as 10 microg of the IL-12 DNA plasmid followed by
      electroporation prevents squamous cell carcinoma (SCCVII) tumor establishment in
      up to 40% of experimental animals and reduces the volume of established tumors by
      75% compared to controls (P<.05). By comparison, there was no difference in tumor
      growth observed between IL-12 injection alone and injection of empty vector with
      or without electroporation. The induction of antitumor activity by i.m.
      electroporation delivery of the IL-12 gene is associated with an increase in IL
      12 expression in muscle and serum. The level of IL-12 expression in muscle and
      serum was 1500 pg/tibialias muscle and 170 pg/mL serum, respectively, at day 6,
      after the gene was delivered by electroporation. In contrast, the level of IL-12
      when the gene was injected without electroporation was hardly detectable after
      subtracting the background level of IL-12 detected in naive mice. The high level
      of IL-12 expression led to a 170-fold induction of IFN-gamma expression in serum
      at day 6 after i.m. electroporation delivery of IL-12 DNA plasmid, which was
      equal to 1450 pg/mL in the serum. The induction of antitumor activity by i.m.
      electroporation delivery of the IL-12 gene also correlates with increased CD8+ T
      cell population in peripheral blood but not in spleen. Our findings suggest that
      i.m. delivery of IL-12 gene using electroporation is an effective method of
      inducing a systemic antitumor response against SCC.

PMID- 11332986
TI  - Effective infection, apoptotic cell killing and gene transfer of human hepatoma
      cells but not primary hepatocytes by parvovirus H1 and derived vectors.
AB  - Autonomous parvoviruses preferentially replicate in and kill in vitro-transformed
      cells and reduce the incidence of spontaneous and implanted tumors in animals.
      Because of these natural oncotropic and oncolytic properties, parvoviruses
      deserve to be considered as potential antitumor vectors. Here, we assessed
      whether parvovirus H1 is able to kill human hepatoma cells by induction of
      apoptosis but spares primary human liver cells, and whether the former cells can
      efficiently be transduced by H1 virus-based vectors. Cell death, infectivity, and
      transgene transduction were investigated in Hep3B, HepG2, and Huh7 cells and in
      primary human hepatocytes with natural and recombinant H1 virus. All hepatoma
      cells were susceptible to H1 virus-induced cytolyis. Cell death correlated with
      H1 virus DNA replication, nonstructural protein expression, and with
      morphological features of apoptosis. H1 virus-induced apoptosis was more
      pronounced in p53-deleted Hep3B and p53-mutated Huh7 cells than in HepG2 cells
      which express wild-type p53. In Hep3B cells, apoptosis was partially inhibited by
      DEVD-CHO, a caspase-3 inhibitor. In contrast, H1 virus-infected primary
      hepatocytes were neither positive for nonstructural protein expression nor
      susceptible to H1 virus-induced killing. Infection with a recombinant parvovirus
      vector carrying the luciferase gene under control of parvovirus promoter P38 led
      to higher transgene activities in hepatoma cells than in the hepatocytes. Taken
      together, H1 virus kills human hepatoma cells at low virus multiplicity but not
      primary hepatocytes. Thus, recombinant H1 viruses carrying antitumor transgenes
      may be considered as potential therapeutic options for the treatment of
      hepatocellular carcinomas.

PMID- 11332987
TI  - Coxsackievirus-adenovirus receptor expression in ovarian cancer cell lines is
      associated with increased adenovirus transduction efficiency and transgene
      expression.
AB  - The expression of coxsackievirus-adenovirus receptor (CAR) and the integrins
      alpha(v)beta3 and alpha(v)beta5 was analyzed quantitatively (flow cytometry) and
      qualitatively (immunocytochemistry) in five human ovarian cancer cell lines
      (PEO1, PEO4, PEO14, SKOV-3, and OVCAR-3) and three control cell lines (293, HeLa,
      and CHO-K1). The transduction efficiencies were evaluated by adv/rsv-beta-Gal
      transduction followed by X-gal staining. The effects of 17beta-estradiol on cell
      growth, CAR and integrins alpha(v)beta3/5 expression, adenovirus transduction
      efficiency, and cell-killing efficacy of adv/rsv-tk plus ganciclovir were
      determined. The levels of CAR, integrin alpha(v)beta3, and integrin alpha(v)beta5
      showed great variation between the cell lines. Whereas the expression of CAR
      appeared to be essential for and positively correlated with adenovirus
      transduction efficiency, the integrins alpha(v)beta3 and alpha(v)beta5 were not
      absolutely necessary for adenovirus transduction even though their presence may
      facilitate transduction. In PEO4 and PEO1 cells, proliferation was stimulated by
      17beta-estradiol in a dose-dependent manner. In PEO4 cells, and much less
      pronounced in PEO1 cells, this was accompanied by an increase in CAR expression.
      The stimulation of CAR expression was paralleled by an increased transduction
      efficiency resulting in an increased cell-killing efficacy. Our data suggest that
      the expression of CAR is one of the most important prerequisites for successful
      adenovirus-mediated gene therapy of ovarian cancer.

PMID- 11332988
TI  - Kinetic characterization of ribozymes directed against the cisplatin resistance
      associated ABC transporter cMOAT/MRP2/ABCC2.
AB  - The enhanced expression of the human ABC transporter, cMOAT (MRP2/ABCC2), is
      associated with resistance of tumor cells against platinum-containing compounds,
      such as cisplatin. Therefore, cMOAT represents an interesting candidate factor
      for modulation of antineoplastic drug resistance. Two different hammerhead
      ribozymes, which exhibit high catalytic cleavage activities towards specific RNA
      sequences encoding cMOAT, were designed. Cleavage sites of these ribozymes are
      the GUC sites in codons 704 and 708 of the open reading frame in the cMOAT
      specific mRNA molecule. Hammerhead ribozymes were in vitro synthesized using
      bacteriophage T7 RNA polymerase and oligonucleotide primers whereby one primer
      contains a T7 RNA polymerase promoter sequence. cMOAT-encoding substrate RNA
      molecules were created by a reverse transcription polymerase chain reaction using
      RNA prepared from the cisplatin-resistant human ovarian carcinoma cell line
      A2780RCIS overexpressing the cMOAT-encoding transcript. In a cell-free system,
      both anti-cMOAT ribozymes cleaved their substrate in a highly efficient manner at
      a physiologic pH and temperature. The cleavage reaction was dependent on time and
      ribozyme:substrate ratio for determining specific kinetic parameters.

PMID- 11332989
TI  - Selection and characterization of a high-activity ribozyme directed against the
      antineoplastic drug resistance-associated ABC transporter BCRP/MXR/ABCG2.
AB  - Breast cancer resistance protein (BCRP) is a recently identified new member of
      the superfamily of ATP-binding cassette transporters. BCRP is a "half
      transporter" that may homo- or heterodimerize to form an active transport
      complex. A considerable overexpression of BCRP was reported from various atypical
      multidrug-resistant tumor cell lines, in particular from those which were
      established by treatment with mitoxantrone. Thus, BCRP represents a very
      interesting candidate molecule for reversal of a drug-resistant phenotype. Six
      hammerhead ribozymes directed against the BCRP-encoding mRNA were designed and
      tested for their ability to cleave their target molecule. The anti-BCRP ribozymes
      were in vitro synthesized using bacteriophage T7 RNA polymerase and
      oligonucleotide primers whereby one primer contains a T7 RNA polymerase promoter
      sequence. BCRP-encoding substrate RNA molecules were created by a reverse
      transcription polymerase chain reaction using total RNA prepared from the
      atypical multidrug-resistant gastric carcinoma cell line EPG85-257RNOV exhibiting
      a high BCRP mRNA expression level. One anti-BCRP ribozyme was found to show a
      very high endoribonucleolytic cleavage activity at physiologic pH and
      temperature. This ribozyme was characterized in a cell-free system with regard to
      its specific kinetic parameters using large target molecules.

PMID- 11332990
TI  - Regression of primary hepatocarcinoma in cancer-prone transgenic mice by local
      interferon-gamma delivery is associated with macrophages recruitment and nitric
      oxide production.
AB  - The clinical potential of tumor therapies must be evaluated using animal models
      closely resembling human cancers. We investigated the impact of locally delivered
      interferon-gamma (IFN-gamma) on primary hepatocarcinoma spontaneously developed
      by T-SV40 transgenic mice. A single intratumor injection of adenovirus IFN-gamma
      was sufficient enough to induce in vivo production of biologically active IFN
      gamma, as assessed by STAT1 activation. IFN-gamma secretion led to the regression
      of primary tumor, principally by apoptosis of tumor hepatocytes. The lack of T
      cells infiltrates in the liver upon treatment excluded a role of a specific
      immune response. In contrast, indirect pathways may include tumoricidal function
      of macrophages. Indeed, they were massively recruited in the entire liver under
      IFN-gamma treatment; transmigration through hepatic blood vessels could be
      observed and co-localization with damaged hepatocytes was obvious. This
      correlated with nonparenchymal liver cell iNOS expression and high level of NO in
      hepatic extracts. Moreover, in vitro experiments showed that NO releasing agents
      induced cell death of freshly isolated tumor hepatocytes, suggesting that NO
      could be one of the major effector molecules. Altogether, these observations
      defined an important role of IFN-gamma in controlling tumor development in a
      model of primary hepatocarcinoma.

PMID- 11332991
TI  - Improvement of nonviral p53 gene transfer in human carcinoma cells using
      glucosylated polyethylenimine derivatives.
AB  - Polyethylenimine (PEI) derivatives are potent polycationic nonviral vectors for
      gene transfer. The gene transfer efficiency of glucosylated and galactosylated
      PEI derivatives was optimized using green fluorescent protein gene as reporter
      gene in FaDu and PANC3 human carcinoma cell lines. Glucosylated or galactosylated
      PEI derivatives were found to be slightly less cytotoxic than unsubstituted PEI.
      Gene transfer efficiency was found to be related to DNA/cell number ratio and
      optimal gene transfer efficiency was achieved at 4 microg DNA/10(5) cells. PEI
      DNA complexes were found to enter cells rapidly and were detected into
      cytoplasmic vesicles 2 hours post-transfection. Green fluorescent protein gene
      expression was detected 4-6 hours after transfection and reached maximal value 24
      hours post-transfection. The results achieved demonstrated that glucosylated PEI
      yield higher and longer gene transfer efficiency than unsubstituted PEI. Using
      glucosylated PEI allowed to achieve significant gene transfer in more than 10% of
      the total cell population for more than 4 days. These data were then applied to
      p53 gene transfer in PANC3 cells bearing p53 gene deletion and consequently
      unable to initiate apoptosis. Using glucosylated PEI, p53 gene transfer was
      successfully achieved with subsequent recovery of p53 mRNA expression and
      transient P53 protein expression. P53 protein functionality was further
      demonstrated because transfected cells underwent apoptosis.

PMID- 11332992
TI  - Transfection of dendritic cells (DCs) with the CIITA gene: increase in
      immunostimulatory activity of DCs.
AB  - Dendritic cells (DCs) are the major antigen-presenting cells. They are able to
      present tumor antigens to immunologic effector cells. MHC class II molecules on
      DC surfaces play an important role in priming effector cells against tumor cells
      and their antigens. The transactivator CIITA (MHC class II transactivator) is a
      non-DNA-binding transactivator, which regulates the expression of MHC class II,
      HLA-DM, and invariant chain and behaves as a master controller of constitutive
      and inducible MHC class II gene activation. Here, we transfected DCs with the
      CIITA gene using a novel transfection technique. The vector system consisted of a
      plasmid bound to an adenovirus via poly-L-lysine, which is covalently bound to a
      UV-irradiated adenovirus. After transfection, expression of MHC class II on DCs
      increased from 27% to 75% on day 2 after transfection. Transfected DCs were co
      cultured with immunologic effector cells. Cytotoxicity of effector cells against
      tumor cells increased after co-culture with transfected DCs to 63% compared to
      15% with effector cells co-cultured with irrelevantly transfected DCs (P=.037).
      This effect was dependent on the timing and period of co-culture. In conclusion,
      transfection of DCs led to an increase in antitumoral immunostimulatory capacity
      of DCs. We can further conclude that DCs could be efficiently transfected with
      the CIITA gene. Transfection of DCs led to an increase in antitumoral
      immunostimulatory capacity of DCs and may have a major impact on
      immunotherapeutic protocols for patients with cancer.

PMID- 11332993
TI  - Necrotic, rather than apoptotic, cell death caused by cytochrome P450-activated
      ifosfamide.
AB  - Feline kidney cells were transfected with a vector overexpressing cytochrome P450
      2B1 (CYP2B1). Transfected cells acquired a new specific biochemical activity,
      which could be demonstrated by a rapid CYP2B1 detection assay and showed
      selective sensitivity to the antitumorigenic prodrug ifosfamide (IFO). Further,
      the cell-killing effect was also mediated on nonmodified cells like feline kidney
      cells, mouse lymphoma, and human pancreatic cells in the vicinity of the CYP2B1
      expressing cells due to the diffusible nature of the activated IFO metabolites.
      One of these, phosphoramide mustard, causes interstrand DNA cross-linking and it
      has been thought that the inability to repair this damage results in apoptosis.
      Surprisingly, our results clearly demonstrate a necrotic mechanism of IFO-induced
      cell death. This may have important implications for the activation of the immune
      system during CYP2B1/IFO suicide gene therapy of cancer.

PMID- 11332994
TI  - Construction and characterization of recombinant adenoviruses expressing human
      BRCA1 or murine Brca1 genes.
AB  - Recombinant adenoviruses expressing human BRCA1 (AdBRCA1), murine Brca1
      (AdBrca1), three clinically relevant human mutant BRCA1 proteins (t340, C61G, and
      1853Stop), or a murine Brca1 C-terminal deletion mutant were constructed and
      evaluated in vitro. These recombinants were capable of transducing high-level
      transgene expression to a wide variety of cell lines in vitro. Three independent
      methods were utilized to monitor cell growth following transduction with these
      recombinants. High-level expression of either the human or mouse wild-type BRCA1
      protein was incompatible with maximal levels of cell growth. AdBRCA1 transduction
      inhibited the outgrowth of several human breast and ovarian cell lines in colony
      formation assays. Flow cytometric analysis revealed an accumulation of the
      transduced cells in the G0/G1 phase of the cell cycle. This BRCA1-mediated
      accumulation of cells in G0/G1 was accompanied by an increase in the cellular
      level of hypophosphorylated pRB. Ad mutant BRCA1 t340, C61G, and 1853Stop viruses
      were impaired, to varying degrees, in their ability to transduce a growth
      arrested state to the target cells. Using these same three criteria,
      overexpression of murine Brca1 by AdBrca1 was also capable of transducing a
      growth-arrested state to human cells. Deletion of the C-terminus of Brca1
      diminished this activity. This panel of adenoviruses may be useful reagents as
      part of an approach to understand the function of BRCA1/Brca1 in normal breast
      and ovary and help to define the tumor suppressor defect (s) conferred by
      clinical BRCA1 mutations in breast and ovarian cell tumorigenesis.

PMID- 11332995
TI  - Bridging the gap in San Francisco: the process of integrating harm reduction and
      traditional substance abuse services.

PMID- 11332996
TI  - Integrating harm reduction therapy and traditional substance abuse treatment.
AB  - One-size-fits-all therapy has not worked well for a majority of substance users
      seeking help. New approaches to substance abuse treatment are desperately needed.
      Traditional models of service delivery offer little, if any, help to people who
      may not choose abstinence as a goal. To address this concern, the Bridging the
      Gap Conference was sponsored by the San Francisco Department of Public Health.
      The overall goals of the conference were to improve standards of care, develop
      best practice principles for integrating harm reduction approaches into
      traditional substance abuse services, and increase the accessibility of quality
      services to people in need of alcohol and drug treatment. G. Alan Marlatt gave a
      keynote address on the integration of harm reduction therapy into traditional
      treatment services, an expanded version of which is presented in this article.
      Such integration would broaden the scope of services available to a larger group
      of consumers of substance abuse treatment. Furthermore, harm reduction therapy
      would infuse traditional treatment practices with scientifically-based pragmatism
      that pays close attention to individual and community public health needs.
      Because of its tolerance of treatment goals other than abstinence, harm reduction
      therapy offers the greatest hope to expand the availability of substance abuse
      services to people who have not benefited from traditional abstinence-based
      treatment models.

PMID- 11332997
TI  - Strategies for implementation of harm reduction in treatment settings.
AB  - Harm reduction is a set of strategies that we all use everyday to protect us from
      the harms of living in a complex world. Central to the principles of harm
      reduction is the need to respect the client's autonomy and develop a relationship
      of mutual collaboration with the goal of reducing drug- and alcohol-related harm.
      Additional principles stress the need to develop a hierarchy of client needs, a
      list that includes all other services, with the importance for each set by the
      client. Harm reduction implementation includes a range of interventions including
      abstinence. Some interventions are controversial, including needle exchange, but
      most are traditional health promotion activities such as videos, health fairs,
      and drug education. Essential to implementing harm reduction is a recognition
      that, even for those who wish to become abstinent, this goal is difficult to
      achieve and maintain. We must acknowledge this and stop the practice of imposing
      punitive sanctions on clients who use drugs while in treatment. Exclusion or
      expulsion from treatment settings does nothing to reduce drug use and greatly
      increases the harm to the client. In conclusion, just as we need to respect
      diversity among our clients, staff must find a way to respect each others' ideas
      and concerns as we develop new ways to implement harm reduction in our work.

PMID- 11332998
TI  - Treatment of dually diagnosed clients.
AB  - Up to 80% of people with mental and emotional disorders have abused or will abuse
      street drugs or alcohol at some point in their lives. Similarly, over half of
      people with substance use disorders are also diagnosed with a mental disorder at
      some point. In clinical populations and institutional settings, the numbers are
      far higher. The term dual diagnosis (coexisting mental and substance use
      disorders) refers to a large and complex group of people. This article addresses
      general issues regarding the complexities of dual diagnosis--differential
      diagnosis, the difficulty of achieving abstinence for people who perceive
      significant benefits from drug use, and the problems due to the historical split
      between the mental health and substance abuse treatment systems. Harm reduction,
      an approach to treating drug-using clients that focuses on the damage done by
      drugs and alcohol without insisting on abstinence from all psychoactive
      substances, can offer a useful way of conceptualizing treatment of dual
      diagnosis. A treatment group specifically designed for dually diagnosed clients
      is described. This group, inspired by the idea that changes in addictive behavior
      occur in a series of stages and that motivation can be influenced by the quality
      of the relationship with the treatment provider, uses a drop-in structure to
      provide low-threshold access to supportive treatment, to meet clients "where they
      are."

PMID- 11332999
TI  - Substance use management: a harm reduction-principled approach to assisting the
      relief of drug-related problems.
AB  - Disease (particularly HIV) has increased our motivation to reconsider how the
      current help system deals with drug-related problems. A more concrete focus on
      disease prevention as an additional goal has, for many, lead to a reevaluation of
      the goals of drug help work. Such a critical examination shows how much there is
      to improve within the system even in the absence of blood borne disease.
      Integrating the heart of harm reduction--respecting work on any positive change
      as a person defines it for his/herself--into treatment fashions a health
      sensitive alternative to the predominant practice of abstinence-only assistance
      for the relief of drug problems. This new approach is called substance use
      management (SUM), as it no longer requires abstinence but instead focuses on a
      range of options for improvements while still including abstinence among the
      possible self-selected outcomes. SUM is suggested as a framework for change
      within the treatment system that would maximize treatment's constructive impact,
      cost-effectiveness and maturation as a distinct discipline that can appropriately
      attract support and gain stature for making society healthier. This article
      describes a formalized system for applying some of the main principles of harm
      reduction within the treatment system. Viable options for a SUM treatment focus
      are suggested herein as well as a critical process, based on respect and
      collaboration, for use with these options.

PMID- 11333000
TI  - Spiritual and religious support in recovery from addiction among HIV-positive
      injection drug users.
AB  - The current study examined the association between support and comfort derived
      from religion or spirituality and abstinence from illicit drugs in a sample of 43
      HIV-positive injection drug users entering a methadone maintenance program.
      Patients with high ratings of perceived spiritual or religious support were
      abstinent from illicit drugs significantly longer during the first six months of
      methadone maintenance than were patients with lower ratings. Controlling for the
      influence of pretreatment variables (addiction and psychiatric severity, CD4
      count, social support, and optimism), and during-treatment variables (methadone
      dose and attendance at counseling sessions), hierarchical regression analysis
      showed that strength of religious and spiritual support was a significant
      independent predictor of abstinence. These findings suggest that spirituality may
      be an important dimension of patient experience to assess in future addiction
      treatment outcome research.

PMID- 11333001
TI  - Comparison of self-report and hair analysis in detecting cocaine use in a
      homeless/transient sample.
AB  - Detection of current (past 30 days) drug use by analysis of hair was examined
      along with self-reports of current use in a 1994 treatment needs assessment
      survey; the sample was 179 homeless/transient adults in New York state. Results
      of radioimmunoassay of hair (RIAH) were used to evaluate the veracity of self
      reports of current cocaine use. Only 26% of those persons whose hair tested
      positive for cocaine (n=115) admitted to having used cocaine in the past 30 days.
      Subjects eligible for treatment, as indicated by a DSM-III-R diagnosis of cocaine
      dependency, were nearly four times as likely to admit current cocaine use than
      those who were not dependent. These results are consistent with other studies of
      populations at high risk for substance use.

PMID- 11333002
TI  - The impact of substance abuse treatment modality on birth weight and health care
      expenditures.
AB  - During the 1990s, substance abuse treatment programs were developed for pregnant
      women to help improve infant birth outcomes, reduce maternal drug dependency and
      promote positive lifestyle changes. This study compared the relative impact of
      five treatment modalities--residential, outpatient, residential/outpatient,
      methadone and detoxification-only--on infant birth weight and perinatal health
      care expenditures for a sample of 445 Medicaid-eligible pregnant women who
      received treatment in Massachusetts between 1992 and 1997. Costs and outcomes
      were measured using the Addiction Severity Index and data from birth
      certificates, substance abuse treatment records and Medicaid claims. Multiple
      regression was used to control for intake differences between the groups. Results
      showed a near linear relationship between birth weight and amount of treatment
      received. Women who received the most treatment (the residential/outpatient
      group) delivered infants who were 190 grams heavier than those who received the
      least treatment (the detoxification-only group) for an additional cost of
      $17,211. Outpatient programs were the most cost-effective option, increasing
      birth weight by 139 grams over detoxification-only for an investment of only
      $1,788 in additional health care and treatment costs. A second regression using
      five intermediate treatment outcomes--prenatal care, weight gain, relapse,
      tobacco use and infection--suggested that increases in birth weight were due
      primarily to improved nutrition and reduced drug use, behaviors which are perhaps
      more easily influenced in residential settings.

PMID- 11333003
TI  - A case study of employment case management with chronically unemployed methadone
      maintained clients.
AB  - Employment interventions implemented in drug treatment programs have been
      marginally successful, but few interventions have been found to address the needs
      of chronically unemployed clients. Employment case management (ECM) is a
      comprehensive employment intervention strategy designed to motivate chronically
      unemployed persons to engage in work, assist in job placement, and provide post
      employment support through workforce integration, while maintaining progress in
      drug treatment. This clinical case study reports on a convenience sample of 10
      chronically unemployed methadone maintained clients who voluntarily enrolled in
      the ECM project. Clients received individual ECM services for a period of 26
      weeks. Clients were assessed at two- and eight-month follow-up intervals. Nine of
      the 10 clients were employed at the two-month follow-up assessment and six
      maintained employment at the eight-month follow-up. Moreover, three clients were
      able to successfully transition from welfare to competitive private sector
      employment. Preliminary data suggest that ECM may be an effective intervention
      strategy to help chronically unemployed methadone clients obtain and maintain
      employment. Qualitatively, clients reported that post employment intervention
      services such as motivational counseling, problem solving, and employer advocacy
      helped sustain employment.

PMID- 11333004
TI  - Testing Cermak's hypothesis: is dissociation the mediating variable that links
      substance abuse in the family of origin with offspring codependency?
AB  - This is a pilot study of substance abuse in the family of origin and its relation
      to offspring dissociation and offspring codependency. Cermak contends that
      substance abuse in the family of origin exposes offspring to trauma, that
      exposure to trauma in the family of origin engenders offspring dissociation, and
      that dissociation is the process underlying offspring codependency. Assuming that
      substance abuse in the family of origin exposes offspring to trauma, this
      experiment tested the hypothesis that dissociation mediates the relationship
      between substance abuse in the family of origin and offspring codependency.
      Although it was found that substance abuse in the family of origin, offspring
      dissociation, and offspring codependency were associated, no support was found
      for the prediction that dissociation mediates the relationship between substance
      abuse in the family of origin and offspring codependency. Replications are called
      for.

PMID- 11333005
TI  - Psychological distress and substance use by adolescent mothers: associations with
      parenting attitudes and the quality of mother-child interaction.
AB  - This study examines associations between psychological distress and alcohol and
      drug use across the first five years of raising a child and parenting quality at
      child age six for 185 adolescent mothers. Overall, alcohol and other drug use in
      this sample was relatively low, but drug use was associated with more mother
      reported unrealistic expectations of child behavior and more attributions of
      child intent to annoy parent by misbehaving. Maternal psychological distress was
      associated with maternal reports of negative control (yelling, pushing, spanking,
      etc.), and alcohol use moderated the association between psychological distress
      and negative control. At low levels of alcohol use, more maternal distress was
      associated with greater negative control; at higher levels of alcohol use,
      maternal distress was not related to negative control, but the absolute level of
      negative control was similar to that reported by more distressed mothers. Neither
      psychological distress nor alcohol and other drug use were related to maternal
      behavior during an interaction task. Overall, much stronger associations with
      parenting outcomes were found for an index of maternal vocabulary, compared with
      maternal psychological distress or maternal alcohol and other drug use.

PMID- 11333006
TI  - Opening inspiration for "Bridging the gap: integrating traditional substance
      abuse and harm reduction services" (May 3-4, 1999, San Francisco).

PMID- 11333007
TI  - An "accidental" acute psychosis with ecstasy use.
AB  - Over the last 10 years, Europe has witnessed the development of the ecstasy
      phenomenon; this term is used to describe several products sharing more or less
      the same effects. The most widely used and hence the most well known is 3,4 MDMA,
      but MDA, MDEA, MBDB and even 2CB or nexus are available. The psychopathological
      consequences of MDMA use in man are relatively poorly understood. The case
      reported here involves an acute psychotic episode with residual symptoms after
      six months, with a sudden onset at least 12 hours after taking alcohol and
      ecstasy without realising it, in an individual with no previous psychopathology
      other than a moderate anxiety disorder. Twelve cases of acute psychotic episodes
      after taking ecstasy have been reported in the literature; two after taking the
      drug on two occasions and one after a single use. No authors have examined the
      previous mental state or possible previous psychopathology with any precision.
      The present subject had not displayed any previous psychotic behavior when tested
      with a proven standardized interview technique; this was confirmed by his peers
      and his family. He did, however, show signs of social phobia. Although the
      personality of an individual is a factor in taking a drug, and probably in the
      quality of the psychotropic effects experienced, a host of arguments favor the
      appearance of psychotic symptoms de novo, which were probably related to direct
      toxicity by MDMA and/or its metabolites on the serotoninergic neurons.

PMID- 11333008
TI  - Inhibiting renin-angiotensin in the brain: the possible therapeutic implications.
AB  - The renin-angiotensin system (RAS) within the brain is involved in central blood
      pressure regulation. Biochemical and neurophysiological studies suggest that the
      brain system is regulated independently of the peripheral RAS and that the system
      may also contribute to blood pressure control and body fluid homeostasis. In
      addition, circulating angiotensin II can exert some of its actions through the
      stimulation of angiotensin subtype 1 (AT1) and subtype 2 (AT2) receptors within
      the brain. As in peripheral tissues, the AT1 receptor mediates the central
      actions of angiotensin II on osmotic control and blood pressure regulation. The
      AT2 receptor appears to be involved in brain development and neuronal
      regeneration, but may also modulate some effects of central AT1 receptor
      stimulation. Selective non-peptide antagonists of the AT1 receptor have been
      shown to inhibit not only peripheral, but also central AT1 receptors after
      systemic application. In animal models, treatment with AT1 receptor antagonists
      proved to be beneficial with respect to stroke incidence and outcome. Other
      animal studies have shown that the AT1 receptor antagonists enable endogenous
      angiotensin II to stimulate nerve generation via AT2 receptors.

PMID- 11333009
TI  - Renal effects of angiotensin II receptor antagonists.
AB  - Among the many roles that angiotensin II plays in the kidney, one of the most
      important is the direct and indirect regulation of sodium excretion. Angiotensin
      II is produced within the kidney, where concentrations appear to be far in excess
      of those detected in plasma. High levels of angiotensin II subtype 1 receptors
      have been detected on the luminal side of the tubular cells in the proximal
      convoluted tubule, and these have been implicated in the regulation of sodium
      excretion. This portion of the nephron is responsible for the reabsorption of 65%
      of filtered sodium. It is, therefore, reasonable to assume that blockade of these
      receptors, using non-peptide angiotensin II receptor antagonists, will bring
      about an increase in renal excretion of sodium. There is, however, the
      possibility that, if the effect is small, downstream sites will have the capacity
      to reabsorb the increased sodium delivered to the distal nephron. Studies in
      hypertensive animal models have established that angiotensin II subtype 1
      receptor antagonists stimulate natriuresis. However, the studies that have been
      performed to date in humans are deficient in that they have been conducted in
      normotensive subjects. Also, subjects have only been followed up for 6 or 8 h and
      thus these studies did not examine whether the observed short-term natriuresis
      was followed by an enhanced reabsorption of sodium. Another study, designed to
      overcome the deficiencies of previous studies, has investigated the natriuretic
      effect of telmisartan in hypertensive patients.

PMID- 11333010
TI  - The role of angiotensin II receptor antagonists in the management of diabetes.
AB  - Diabetic nephropathy, which develops in about 30% of patients with diabetes, is a
      progressive condition. It is characterized by increased blood pressure, declining
      glomerular filtration rate and albuminuria. Lowering of blood pressure in
      diabetic patients is associated with reduced cardiovascular risk and renal
      protection. Inhibitors of angiotensin-converting enzyme (ACE) are the current
      gold standard treatment for hypertension in patients with type I diabetes
      because, in addition to their blood pressure lowering ability, they are thought
      to oppose the increased intraglomerular pressure that is mediated in part by
      angiotensin II. The angiotensin II receptor antagonists, a more recently
      developed class of antihypertensive agents, appear to be as effective as ACE
      inhibitors in delaying the progression of renal injury in animal models of
      diabetes. They act by selectively blocking the binding of angiotensin II to the
      AT1 receptor and may, therefore, offer a more complete blockade of the renin
      angiotensin system than ACE inhibitors. The renal and antihypertensive effects of
      this class of drug in patients with diabetes are now being investigated in long
      term clinical trials. The multicentre Diabetics Exposed to Telmisartan And
      EnalaprIL (DETAIL) study is a randomized, double-blind, parallel-group comparison
      of the renal and antihypertensive effects of the angiotensin II receptor
      antagonist telmisartan and the ACE inhibitor enalapril in 272 patients with type
      II diabetes. The primary outcome is change in glomerular filtration rate over the
      5 years of the study.

PMID- 11333011
TI  - Ambulatory blood pressure monitoring to assess the comparative efficacy and
      duration of action of a novel new angiotensin II receptor blocker--telmisartan.
AB  - Although a wide range of antihypertensive agents is available, adequate blood
      pressure control is achieved in only about 25% of hypertensive patients. Poor
      control rates are often due to inadequate patient compliance and unacceptable
      side-effects. The importance of once-daily dosing is now fully acknowledged, but
      it is crucial that therapy when given once a day must be effective at the end of
      the dosing interval to order to minimize the likelihood of sudden cardiac death,
      myocardial infarction and stroke. Ambulatory blood pressure monitoring (ABPM)
      provides a thorough assessment of the blood pressure-lowering characteristics of
      an antihypertensive agent throughout the dosing interval and can more accurately
      evaluate differences in the duration of the antihypertensive effect of different
      agents. Telmisartan, a new angiotensin II receptor antagonist, has been
      extensively studied in clinical trials using ABPM. When compared with
      dihydropyridine calcium antagonists, beta-adrenergic blockers, angiotensin
      converting enzyme inhibitors and other angiotensin II receptor antagonists,
      telmisartan has proved superior in diminishing ambulatory blood pressure
      throughout the 24-h period between doses. Telmisartan also has excellent
      tolerability and in clinical trials demonstrates no increase, irrespective of
      dose level, over placebo in the incidence of adverse events. Thus, telmisartan
      given once daily provides high efficacy and tolerability, and will hopefully
      assist in improving both blood pressure control rates and cardiovascular outcomes
      in the future.

PMID- 11333012
TI  - Angiotensin II receptor antagonists: new paradigms in the treatment of
      hypertension. Introduction.

PMID- 11333013
TI  - The comparative pharmacology of angiotensin II receptor antagonists.
AB  - Several orally active non-peptide angiotensin II subtype 1 (AT1) receptor
      antagonists are now available for the treatment of hypertension. These agents
      have a common mechanism of action--blockade of the binding of angiotensin II to
      the subtype 1 receptor--and their binding to this receptor is generally
      insurmountable. There are some pharmacokinetic and pharmacodynamic differences
      between these antagonists, which may reflect in their clinical efficacy,
      especially at the end of the dosing interval. Losartan has an active metabolite
      that prolongs its duration of action, and candesartan cilexetil requires
      conversion to an active form after administration. Telmisartan has the longest
      duration of action, with a terminal elimination half-life of around 24 h in
      comparison with 11-15 h for irbesartan, the agent with the next longest half
      life. The long duration of action and insurmountable binding to the receptor may
      be related to the slow dissociation kinetics of the antagonists from the AT1
      receptor. Comparative clinical studies suggest that at the recommended dose
      losartan, the original drug in this class, has a lower antihypertensive efficacy
      than the newer agents, such as telmisartan. It is possible that these differences
      between angiotensin II receptor antagonists are due to variations in the degree
      and duration of receptor blockade, and may be of clinical significance with
      regard to the cardioprotective and renoprotective effects of this class of
      antihypertensive agents.

PMID- 11333014
TI  - An extended structural signature for the tRNA anticodon loop.
AB  - Anticodon hairpins are structural motifs with contradictory functions. The
      recognition by aminoacyl synthetases implies extended interactions with the
      anticodon base triplet and thus, usually, an unfolding of the anticodon loop. The
      recognition by the ribosome and cognate interaction with a mRNA codon implies, on
      the other hand, the formation of a mini-helix with a canonical anticodon hairpin
      structure as observed by crystallography and NMR. To be able to understand the
      various properties of this motif, a precise description of its structural
      conservation is required. Here, on the basis of phylogenetic, structural, and
      molecular dynamics data, we discuss a conserved interaction established between
      the ribose of the U33 and the base at position 35, either a purine or a
      pyrimidine. This interaction involves the hydrogen bonding donor or acceptor
      potential of the hydroxyl group of U33 and has to be integrated in an extended
      definition of the anticodon hairpin. The extended structural signature provides
      also an explanation for the role played by pseudouridines at position 35.

PMID- 11333015
TI  - Activation of a cryptic 5' splice site by U1 snRNA.
AB  - In the course of analyzing 5' splice site mutations in the second intron of
      Schizosaccharomyces pombe cdc2, we identified a cryptic 5' junction containing a
      nonconsensus nucleotide at position +2. An even more unusual feature of this
      cryptic 5' junction was its pattern of activation. By analyzing the profile of
      splicing products for an extensive series of cdc2 mutants in the presence and
      absence of compensatory U1 alleles, we have obtained evidence that the natural 5'
      splice site participates in activation of the cryptic 5' splice site, and that it
      does so via base pairing to U1 snRNA. Furthermore, the results of follow-up
      experiments strongly suggest that base pairing between U1 snRNA and the cryptic
      5' junction itself plays a dominant role in its activation. Most remarkably, a
      mutant U1 can activate the cryptic 5' splice site even in the presence of a wild
      type sequence at the natural 5' junction, providing unambiguous evidence that
      this snRNA redirects splicing via base pairing. Although previous work has
      demonstrated that U5 and U6 snRNAs can activate cryptic 5' splice sites through
      base pairing interactions, this is the first example in which U1 snRNA has been
      implicated in the final selection of a cryptic 5' junction.

PMID- 11333016
TI  - The evolutionarily conserved region of the U snRNA export mediator PHAX is a
      novel RNA-binding domain that is essential for U snRNA export.
AB  - In metazoa, a subset of spliceosomal U snRNAs are exported from the nucleus after
      transcription. This export occurs in a large complex containing a U snRNA, the
      nuclear cap binding complex (CBC), the leucine-rich nuclear export signal
      receptor CRM1/Xpo1, RanGTP, and the recently identified phosphoprotein PHAX
      (phosphorylated adaptor for RNA export). Previous results indicated that PHAX
      made direct contact with RNA, CBC, and Xpo1 in the U snRNA export complex. We
      have now performed a systematic characterization of the functional domains of
      PHAX. The most evolutionarily conserved region of PHAX is shown to be a novel RNA
      binding domain that is essential for U snRNA export. In addition, PHAX contains
      two major nuclear localization signals (NLSs) that are required for its recycling
      to the nucleus after export. The interaction domain of PHAX with CBC is at least
      partly distinct from the RNA-binding domain and the NLSs. Thus, the different
      interaction domains of PHAX allow it to act as a scaffold for the assembly of U
      snRNA export complexes.

PMID- 11333017
TI  - Basis for regulated RNA cleavage by functional analysis of RNase L and Ire1p.
AB  - RNase L and Ire1p are members of a superfamily of regulated endoribonucleases
      that play essential roles in mediating diverse types of cellular stress
      responses. 2'-5' oligoadenylates, produced in response to interferon treatment
      and viral double-stranded RNA, are necessary to activate RNase L. In contrast,
      unfolded proteins in the endoplasmic reticulum activate Ire1p, a transmembrane
      serine/threonine kinase and endoribonuclease. To probe their similarities and
      differences, molecular properties of wild-type and mutant forms of human RNase L
      and yeast Ire1p were compared. Surprisingly, RNase L and Ire1p showed mutually
      exclusive RNA substrate specificity and partially overlapping but not identical
      requirements for phylogenetically conserved amino acid residues in their nuclease
      domains. A functional model for RNase L was generated based on the comparative
      analysis with Ire1p that assigns novel roles for ankyrin repeats and kinase-like
      domains.

PMID- 11333018
TI  - A mammalian sequence-dependent upstream open reading frame mediates polyamine
      regulated translation in yeast.
AB  - In mammals, control of S-adenosylmethionine decarboxylase (AdoMetDC) translation
      is one component of a feedback network that regulates intracellular levels of the
      polyamines, spermidine, and spermine. AdoMetDC mRNA from mammals contains a
      highly conserved upstream open reading frame (uORF) within its leader sequence
      that confers polyamine-regulated suppression of translation on the associated
      downstream cistron. This regulation is mediated through an interaction that
      depends on the amino acid sequence of the uORF-encoded hexapeptide. It remains to
      be shown whether polyamines participate directly in this interaction or
      indirectly through a specialized signal transduction pathway. We show that
      Saccharomyces cerevisiae does not have a uORF associated with its AdoMetDC gene
      (SPE2) and that ribosome loading on the SPE2 mRNA is not positively influenced by
      polyamine depletion, as it is in mammalian cells. Nevertheless, the mammalian
      AdoMetDC uORF, when introduced into a polyamine auxotroph of yeast, conferred
      polyamine regulation of both translational efficiency and ribosome loading on the
      associated mRNA. This regulatory activity depended on the amino acid sequence
      encoded by the fourth and fifth codons of the uORF, as in mammalian cells. The
      fact that the regulatory properties of this mammalian translational control
      element are quite similar in both mammalian and yeast cells suggests that a
      specialized signal transduction pathway is not required. Rather, it seems likely
      that polyamines may be directly participating in an interaction between the uORF
      encoded peptide and a constitutive component of the translation machinery, which
      leads to inhibition of ribosome activity.

PMID- 11333020
TI  - The effect of cytidine on the structure and function of an RNA ligase ribozyme.
AB  - A cytidine-free ribozyme with RNA ligase activity was obtained by in vitro
      evolution, starting from a pool of random-sequence RNAs that contained only
      guanosine, adenosine, and uridine. This ribozyme contains 74 nt and catalyzes
      formation of a 3',5'-phosphodiester linkage with a catalytic rate of 0.016 min(
      1). The RNA adopts a simple secondary structure based on a three-way junction
      motif, with ligation occurring at the end of a stem region located several
      nucleotides away from the junction. Cytidine was introduced to the cytidine-free
      ribozyme in a combinatorial fashion and additional rounds of in vitro evolution
      were carried out to allow the molecule to adapt to this added component. The
      resulting cytidine-containing ribozyme formed a 3',5' linkage with a catalytic
      rate of 0.32 min(-1). The improved rate of the cytidine-containing ribozyme was
      the result of 12 mutations, including seven added cytidines, that remodeled the
      internal bulge loops located adjacent to the three-way junction and stabilized
      the peripheral stem regions.

PMID- 11333019
TI  - The requirement for eukaryotic initiation factor 4A (elF4A) in translation is in
      direct proportion to the degree of mRNA 5' secondary structure.
AB  - Eukaryotic initiation factor (elF) 4A functions as a subunit of the initiation
      factor complex elF4F, which mediates the binding of mRNA to the ribosome. elF4A
      possesses ATPase and RNA helicase activities and is the prototype for a large
      family of putative RNA helicases (the DEAD box family). It is thought that the
      function of elF4A during translation initiation is to unwind the mRNA secondary
      structure in the 5' UTR to facilitate ribosome binding. However, the evidence to
      support this hypothesis is rather indirect, and it was reported that elF4A is
      also required for the translation of mRNAs possessing minimal 5' UTR secondary
      structure. Were this hypothesis correct, the requirement for elF4A should
      correlate with the degree of mRNA secondary structure. To test this hypothesis,
      the effect of a dominant-negative mutant of mammalian elF4A on translation of
      mRNAs with various degrees of secondary structure was studied in vitro. Here, we
      show that mRNAs containing stable secondary structure in the 5' untranslated
      region are more susceptible to inhibition by the elF4A mutant. The mutant protein
      also strongly inhibits translation from several picornavirus internal ribosome
      entry sites (IRES), although to different extents. UV crosslinking of elF4F
      subunits and elF4B to the mRNA cap structure is dramatically reduced by the elF4A
      mutant and RNA secondary structure. Finally, the elF4A mutant forms a more stable
      complex with elF4G, as compared to the wild-type elF4A, thus explaining the
      mechanism by which substoichiometric amounts of mutant elF4A inhibit translation.

PMID- 11333021
TI  - X-ray crystallographic observation of "in-line" and "adjacent" conformations in a
      bulged self-cleaving RNA/DNA hybrid.
AB  - The RNA strand in an RNA/DNA duplex with unpaired ribonucleotides can undergo
      self-cleavage at bulge sites in the presence of a variety of divalent metal ions
      (Husken et al., Biochemistry, 1996, 35:16591-16600). Transesterification proceeds
      via an in-line mechanism, with the 2'-OH of the bulged nucleotide attacking the
      3'-adjacent phosphate group. The site-specificity of the reaction is most likely
      a consequence of the greater local conformational freedom of the RNA backbone in
      the bulge region. A standard A-form backbone geometry prohibits formation of an
      in-line arrangement between 2'-oxygen and phosphate. However, the backbone in the
      region of an unpaired nucleotide appears to be conducive to an in-line approach.
      Therefore, the bulge-mediated phosphoryl transfer reaction represents one of the
      simplest RNA self-cleavage systems. Here we focus on the conformational features
      of the RNA that underlie site-specific cleavage. The structures of an RNA/DNA
      duplex with single ribo-adenosyl bulges were analyzed in two crystal forms,
      permitting observation of 10 individual conformations of the RNA bulge moiety.
      The bulge geometries cover a range of relative arrangements between the 2'-oxygen
      of the bulged nucleotide and the P-O5' bond (including adjacent and near in-line)
      and give a detailed picture of the conformational changes necessary to line up
      the 2'-OH nucleophile and scissile bond. Although metal ions are of crucial
      importance in the catalysis of analogous cleavage reactions by ribozymes, it is
      clear that local strain or conformational flexibility in the RNA also affect
      cleavage selectivity and rate (Soukup & Breaker, RNA, 1999, 5:1308-1325). The
      geometries of the RNA bulges frozen out in the crystals provide snapshots along
      the reaction pathway prior to the transition state of the phosphoryl transfer
      reaction.

PMID- 11333022
TI  - The sequence complementarity between HIV-1 5' splice site SD4 and U1 snRNA
      determines the steady-state level of an unstable env pre-mRNA.
AB  - HIV-1 env expression from certain subgenomic vectors requires the viral
      regulatory protein Rev, its target sequence RRE, and a 5' splice site upstream of
      the env open reading frame. To determine the role of this splice site in the 5'
      splice-site-dependent Rev-mediated env gene expression, we have subjected the HIV
      1 5' splice site, SD4, to a mutational analysis and have analyzed the effect of
      those mutations on env expression. The results demonstrate that the overall
      strength of hydrogen bonding between the 5' splice site, SD4, and the free 5' end
      of the U1 snRNA correlates with env expression efficiency, as long as env
      expression is suboptimal, and that a continuous stretch of 14 hydrogen bonds can
      lead to full env expression, as a result of stabilizing the pre-mRNA. The U1
      snRNA-mediated stabilization is independent of functional splicing, as a mismatch
      in position +1 of the 5' splice site that led to loss of detectable amounts of
      spliced transcripts did not preclude stabilization and expression of the
      unspliced env mRNA, provided that Rev enables its nuclear export. The nucleotides
      capable of participating in U1 snRNA:pre-mRNA interaction include positions -3 to
      +8 of the 5' splice site and all 11 nt constituting the single-stranded 5' end of
      U1 snRNA. Moreover, env gene expression is significantly decreased upon the
      introduction of point mutations in several upstream GAR nucleotide motifs, which
      are mediating SF2/ASF responsiveness in an in vitro splicing assay. This suggests
      that the GAR sequences may play a role in stabilizing the pre-mRNA by
      sequestering U1 snRNP to SD4.

PMID- 11333023
TI  - Fending off decay: a combinatorial approach in intact cells for identifying mRNA
      stability elements.
AB  - The strategy of systematic evolution, whereby nucleic acid sequences or
      conformers can be selected and amplified from a randomized population, has been
      exploited by many research groups for numerous purposes. It is, however, a
      technique largely performed in vitro, under nonphysiological conditions. We have
      now modified this in vitro approach to accomplish selection in growing cells.
      Here, we report that this new methodology has been used in vivo to select RNA
      elements that confer increased transcript stability. A randomized cassette was
      embedded in a 3'-untranslated region (UTR), downstream from the luciferase
      reporter open reading frame. A heterogeneous population of capped luciferase mRNA
      was then generated by in vitro transcription. Human liver Hep G2 cells were
      electroporated with this population of luciferase mRNA and total cytoplasmic RNA
      was isolated after varying lengths of incubation. Following RT-PCR, the 3' UTR
      was used to reconstruct a new population of luciferase templates, permitting
      subsequent cycles of in vitro transcription, electroporation, RNA isolation, and
      RT-PCR. Increasing the incubation time at each cycle before RNA isolation imposed
      selection for stable transcripts. The functional half-life of the luciferase mRNA
      population increased from 55 to 140 min after four cycles. Subsequent sequencing
      of the selected 3' UTRs revealed G-U rich elements in clones with extended
      chemical and functional half-lives.

PMID- 11333024
TI  - Mammalian heat shock p70 and histone H4 transcripts, which derive from naturally
      intronless genes, are immune to nonsense-mediated decay.
AB  - Nonsense-mediated decay (NMD), also called mRNA surveillance, is an
      evolutionarily conserved pathway that degrades mRNAs that prematurely terminate
      translation. To date, the pathway in mammalian cells has been shown to depend on
      the presence of a cis-acting destabilizing element that usually consists of an
      exon-exon junction generated by the process of pre-mRNA splicing. Whether or not
      mRNAs that derive from naturally intronless genes, that is, mRNAs not formed by
      the process of splicing, are also subject to NMD has yet to be investigated. The
      possibility of NMD is certainly reasonable considering that mRNAs of
      Saccharomyces cerevisiae are subject to NMD even though most derive from
      naturally intronless genes. In fact, mRNAs of S. cerevisiae generally harbor a
      loosely defined splicing-independent destabilizing element that has been proposed
      to function in NMD analogously to the spliced exon-exon junction of mammalian
      mRNAs. Here, we demonstrate that nonsense codons introduced into naturally
      intronless genes encoding mouse heat shock protein 70 or human histone H4 fail to
      elicit NMD. Failure is most likely because each mRNA lacks a cis-acting
      destabilizing element, because insertion of a spliceable intron a sufficient
      distance downstream of a nonsense codon within either gene is sufficient to
      elicit NMD.

PMID- 11333025
TI  - Purification of Drosophila snRNPs and characterization of two populations of
      functional U1 particles.
AB  - U1 snRNP is required at an early stage during assembly of the spliceosome, the
      dynamic ribonucleoprotein (RNP) complex that performs nuclear pre-mRNA splicing.
      Here, we report the purification of U1 snRNP particles from Drosophila nuclear
      extracts and the characterization of their biochemical properties, polypeptide
      contents, and splicing activities. On the basis of their antigenicity, apparent
      molecular weight, and by peptide sequencing, the Drosophila 70K, SNF, B, U1-C,
      D1, D2, D3, E, F, and G proteins are shown to be integral components of these
      particles. Sequence database searches revealed that both the U1-specific and the
      Sm proteins are extensively conserved between human and Drosophila snRNPs.
      Furthermore, both species possess a conserved intrinsic U1-associated kinase
      activity with identical substrate specificity in vitro. Finally, our results
      demonstrate that a second type of functional U1 particle, completely lacking the
      U1/U2-specific protein SNF and the associated protein kinase activity, can be
      isolated from cultured Kc cell or Canton S embryonic nuclear extracts. This work
      describes the first characterization of a purified Drosophila snRNP particle and
      reinforces the view that their activity and composition, with the exception of
      the atypical bifunctional U1-A/U2-B" SNF protein, are highly conserved in
      metazoans.

PMID- 11333026
TI  - Functions of SR proteins in the U12-dependent AT-AC pre-mRNA splicing pathway.
AB  - SR proteins play critical roles in the major pre-mRNA splicing pathway. A second
      pathway processes U12-dependent AT-AC introns. We demonstrate, by biochemical
      complementation, the requirement for SR proteins in splicing of AT-AC introns.
      Whereas SR proteins were sufficient to activate splicing of a P120 AT-AC intron,
      splicing of a sodium channel AT-AC intron required an additional nuclear
      fraction. Individual recombinant SR proteins promoted splicing of both
      substrates, but displayed marked preferences. SR proteins supported basal AT-AC
      splicing, and also splicing stimulation via a downstream enhancer or conventional
      5' splice site. Analysis of chimeric transcripts revealed that information
      dispersed throughout exons and introns dictates SR protein specificity and the
      requirement for the additional nuclear fraction. Thus, SR proteins function in
      both major and minor splicing pathways, and in coordinating the activities of
      both spliceosomes via exon definition. These results suggest that despite the
      substantial differences in intron consensus sequences and in four of the five
      snRNPs in each spliceosome, at least some of the interactions involving SR
      proteins are conserved between the two pathways.

PMID- 11333027
TI  - Translational control by delayed RNA folding: identification of the kinetic trap.
AB  - The maturation or A-protein gene of single-stranded RNA phage MS2 is preceded by
      a 130-nt long untranslated leader. When MS2 RNA folding is at equilibrium, the
      gene is untranslatable because the leader adopts a well-defined cloverleaf
      structure in which the Shine-Dalgarno (SD) sequence of the maturation gene is
      taken up in long-distance base pairing with an upstream complementary sequence
      (UCS). Synthesis of the A-protein takes place transiently while the RNA is
      synthesized from the minus strand. This requires that formation of the inhibitory
      cloverleaf is slow. In vitro, the folding delay was on the order of minutes.
      Here, we present evidence that this postponed folding is caused by the formation
      of a metastable intermediate. This intermediate is a small local hairpin that
      contains the UCS in its loop, thereby preventing or slowing down its pairing with
      the SD sequence. Mutants in which the small hairpin could not be formed made no
      detectable amounts of A-protein and were barely viable. Apparently, here the
      cloverleaf formed quicker than ribosomes could bind. On the other hand, mutants
      in which the small intermediary hairpin was stabilized produced more A-protein
      than wild type and were viable. One hardly growing mutant that could not form the
      metastable hairpin and did not make detectable amounts of A-protein was evolved.
      The emerging pseudo-revertant had selected two second site repressor mutations
      that allowed reconstruction of a variant of the metastable intermediate. The
      pseudo-revertant had also regained the capacity to produce the A-protein.

PMID- 11333028
TI  - Preparation and characterization of biodegradable copolyester-starch based foams.
AB  - Regular (25% amylose) and waxy corn starches blended to various ratios with
      Eastar Bio Copolyester 14766 (EBC) were extruded into loose-fill foams using a
      twin screw extruder. Included in this study were two types of corn starch, three
      levels of EBC content, and three levels of starch moisture content. Waxy starch
      produced foams with greater radial expansions and lower unit and bulk densities
      than regular starch. Regular starch foams had lower water solubility indices
      (WSIs) than waxy starch foams. Foams made of both types of starch possessed
      similar mechanical properties. No differences were observed in compressibilities
      and spring indices of either waxy or regular starch foams. Higher levels of EBC
      addition resulted in less radial expansion and higher unit and bulk densities.
      Foams made with 10% EBC had higher compressibility than foams containing 25% EBC.
      Spring indices of single-piece samples and compressibilities and spring indices
      of bulk samples were not affected by the differences in the level of EBC
      addition. At 19% and 22% of moisture contents, foams had greater radial expansion
      than at 25% moisture content. Unit and bulk densities were not affected by
      variations in moisture content. At 22% moisture content, a lower WSI of 18.5% was
      obtained. At 22% moisture content, softer foams were produced. At all three
      levels of moisture content, no differences were detected in the spring indices.

PMID- 11333029
TI  - Production of glucose oxidase using Aspergillus niger and corn steep liquor.
AB  - Glucose oxidase production was optimized using an isolated strain of Aspergillus
      niger and an economical nutrient source, corn steep liquor (CSL). The culture
      produced 580 +/- 30 units/ml of the enzyme using 70 g/l sucrose as the carbon
      source. Using CSL as the sole nutrient source enzyme synthesis was increased to
      640 +/- 36 units/ml. None of the nitrogen sources (nitrates of calcium, sodium,
      ammonium, potassium and yeast extract, malt extract, and peptone) was beneficial
      to the enzyme synthesis. Aeration and agitation enhanced enzyme synthesis to 850
      +/- 45 units/ml. Glucose oxidase has numerous applications in food industry and
      clinical fields.

PMID- 11333030
TI  - Simulation of low temperature anaerobic digestion of dairy and swine manure.
AB  - The data reported by L.M. Safley, P.W. Westerman [Bioresource Technology 47 (2)
      (1994) 165-171] from the laboratory digestion of dairy and swine manure at
      psychrophilic temperatures (i.e., 10-23 degrees C) have been used to determine
      the response of the latest comprehensive dynamic mathematical model of
      methanogenesis [D.T. Hill, S.A. Cobb, Transactions of the ASAE 39 (2) (1996) 565
      573] in this low temperature range. Extensive performance data from digesters
      using animal waste in this temperature range have been lacking, thus allowing
      limited validation of the comprehensive model. The results of the comprehensive
      model simulations were compared with the actual data reported by Safley and
      Westerman (loc. cit.) and with their empirical regression models. Results
      indicate that the comprehensive model is as accurate as Safley and Westerman's
      models for three of the four cases reported, but shows a great dissimilarity for
      the fourth case.

PMID- 11333031
TI  - Removal of selected metal ions from aqueous solution using modified corncobs.
AB  - The objective of this study was to convert corncobs to metal ion adsorbents for
      wastewater treatment. Ground corncobs were modified with either 0.6 M citric acid
      (CA) or 1.0 M phosphoric acid (PA) to help improve their natural adsorption
      capacity. The effect of a combination of wash and modification treatment was
      tested for corncob adsorption efficiency with five different metal ions (cadmium,
      copper, lead, nickel, zinc) individually or in a mixed solution containing each
      metal at a 20 mM concentration. Results were compared to those of commercial
      resins Amberlite IRC-718, Amberlite 200, Duolite GT-73 and carboxymethylcellulose
      (CMC). Modified corncobs showed the same adsorption efficiency as Duolite GT-73
      for cadmium, copper, nickel and zinc ions and had greater adsorption than CMC for
      nickel and zinc ions. For mixed metals, the modified corncobs exhibited the same
      adsorption efficiency as Duolite GT-73 for cadmium and copper ions and the same
      or higher adsorption than Amberlite IRC-718 for lead ions. Adsorption capacities
      of modified samples were compared to those of Amberlite IRC-718, Amberlite 200
      and Duolite GT-73. Commercial resins generally had higher adsorption capacities
      than modified corncobs. However, the adsorption capacity of modified corncobs for
      copper and lead ions was equivalent to Duolite GT-73, but was lower than for
      Amberlite IRC-718 or Amberlite 200. Depending on the specific metal ion and the
      presence or absence of other metal ions, chemically modified corncobs were at
      least equivalent in adsorption properties to all of the commercial cation
      exchange resins examined in this study.

PMID- 11333032
TI  - In vitro dehalogenation of tetrachloroethylene (PCE) by cell-free extracts of
      Clostridium bifermentans DPH-1.
AB  - Cell-free extracts of Clostridium bifermentans DPH-1 catalyzed
      tetrachloroethylene (PCE) dechlorination. PCE degradation was stimulated by
      addition of a variety of electron donors. Ethanol (0.61 mM) was the most
      effective electron donor for PCE dechlorination. Maximum activity was recorded at
      30 degrees C and pH 7.5. Addition of NADH as a cofactor stimulated enzymatic
      activity but the activity was not stimulated by addition of metal ions. When the
      cell-free enzyme extract was incubated in the presence of titanium citrate as a
      reducing agent, the dehalogenase was rapidly inactivated by propyl iodide (0.5
      mM). The activity of propyliodide-reacted enzyme was restored by illumination
      with a 250 W lamp. The dehalogenase activity was also inhibited by cyanide. The
      substrate spectrum of activity included trichloroethylene (TCE), cis-1,2
      dichloroethylene (cDCE), trans-dichloroethylene, 1,1-dichloroethylene, 1,2
      dichloroethane, and 1,1,2-trichloroethane. The highest rate of degradation of the
      chlorinated aliphatic compounds was achieved with PCE, and PCE was principally
      degraded via TCE to cDCE. Results indicate that the dehalogenase could play a
      vital role in the breakdown of PCE as well as a variety of other chlorinated
      aliphatic compounds.

PMID- 11333033
TI  - The effect of supplementation by different nitrogen sources on the production of
      lactic acid from date juice by Lactobacillus casei subsp. rhamnosus.
AB  - Production of lactic acid from date juice by fermentation has been studied using
      Lactobacillus casei subsp. rhamnosus as the producer organism. The optimum
      substrate concentration, expressed in its glucose content, was 60 g l(-1).
      Various nitrogen sources were compared with yeast extract in terms of their
      efficiency for lactic acid production. None of these nitrogen sources gave lactic
      acid concentrations as high as that obtained with yeast extract. As yeast extract
      supplementation was not economically attractive, different proportions of
      (NH4)2SO4 and yeast extract were used. When the elemental nitrogen ratio
      of(NH4)2SO4 to yeast extract was 4:1, the substrate use and efficiency of lactic
      acid production were the same as in date juice supplemented with 20 g l(-1) yeast
      extract (0:5).

PMID- 11333034
TI  - A further study of the anaerobic biotreatment of malt whisky distillery pot ale
      using an UASB system.
AB  - Pot ale from a pilot-scale malt whisky distillery was treated using a mesophilic
      upflow anaerobic sludge blanket (UASB) digester. Stable operation was observed at
      organic loading rates (OLRs) of 5.46 kg COD/m3 day or less when the pot ale was
      diluted with tap water. Digester failure occurred when undiluted pot ale was
      used, even though OLR was less than 5 kg COD/m3 day. Overall performance was
      worse than that observed previously when UASB digesters were used to treat pot
      ale from a different source supplemented with trace elements. A substantial
      proportion of effluent chemical oxygen demand (COD) was present as volatile fatty
      acids (VFA), particularly during periods of reactor stress, indicating that
      overall performance was limited by the rate of VFA conversion. Wastewater
      alkalinity rose during digestion. The sludge which developed in the reactor was
      flocculent but did not form compact granules.

PMID- 11333035
TI  - Nitrogen budget in Scenedesmus obliquus cultures with artificial wastewater.
AB  - Semicontinuous cultures of Scenedesmus obliquus in artificial wastewater,
      recycled into proteins about 33% and 25% of the dissolved nitrogen missing from
      the medium 24 h after harvesting 50% and 70% of the culture, and replacing the
      volume harvested with fresh medium. The residual dissolved nitrogen
      concentrations were 25% and 43% of the initial, respectively, with an imbalance
      in the mass budget close to 17 and 20 mg N l(-1) d-1. Most or all the nitrogen
      missing was found in an ammonia trap located at the air vent of the closed
      cultures, showing that an important role of microalgae in wastewater treatment is
      that of favouring NH3 stripping due to the photosynthesis-induced pH increases.

PMID- 11333036
TI  - Stable performance of anaerobic digestion in the presence of a high concentration
      of propionic acid.
AB  - An automatically controlled, glucose-fed, anaerobic digester was deliberately
      inhibited by addition of phenol. To overcome the phenol inhibition the feed
      dilution rate was lowered in such a way that the methane yield from glucose was
      kept the same as that under normal conditions. The concentrations of acetic and
      butyric acids remained below 100 mg/l, however, propionic acid accumulated to
      2,750 mg/l. Phenol apparently inhibited all tropic groups of organisms and it was
      shown that the propionic acid was formed from the metabolism of phenol. From the
      nature of the operating strategy, it was deduced that the digester continued to
      convert all the glucose that was supplied to methane showing that propionic acid
      accumulation did not inhibit conversion of glucose to methane. Therefore,
      propionic acid accumulation may be an effect and not a cause of inhibition of the
      anaerobic digestion process.

PMID- 11333037
TI  - Movement of water and heavy metals (Zn, Cu, Pb and Ni) through sand and sandy
      loam amended with biosolids under steady-state hydrological conditions.
AB  - New guidelines for using biosolids in UK agriculture favour the use of enhanced
      treated biosolids, such as dried and composted cakes, due to concerns about the
      potential for transfer of pathogens into the food chain. However, there is a need
      to ensure that their use is environmentally acceptable and does not increase the
      risk to potable water supplies or the food chain from other contaminants such as
      heavy metals and xenobiotic organic chemicals. The objective of this study was to
      determine whether the use of composted and dried mesophilic anaerobically
      digested dewatered (MADD) biosolids would increase the risk of heavy metal
      leaching from cultivated horizons when compared to more conventionally used MADD
      cake. Three biosolids (MADD sewage sludge cake - fresh, dried and composted) were
      mixed with a sand (typic quartzipsamments, %OM = 3.0, pH = 6.5) or a sandy loam
      (typic hapludalf, %OM = 4.8, pH = 7.6) at an application rate equivalent to 250
      kg N/ha/y resulting in loadings of approximately Zn: 6 microg, Cu: 2 microg, Pb:
      5 microg and Ni: 0.2 microg/g of soil dry weight basis. These amended soils were
      repacked into columns (0.4 m by 0.1 m internal diameter) and leaching of Zn, Cu,
      Pb and Ni was investigated following application of two 24 h simulated rainfall
      events of 4.5 mm/h. Water balance data and the use of conservative tracers (Cl-
      and Br ) showed that the hydrological regimes of each core were comparable and,
      thus, unlikely to account for differences in metal leaching observed. Although no
      significant difference (P = 0.05) was observed between biosolid amended and
      control soils, those amended with composted sludge consistently gave higher loss
      of all metals than did the control soils. Total losses of metals from compost
      amended soil over the two rainfall events were in the ranges, Zn:20.5-58.2,
      Cu:9.0-30.5, Pb:24.2-51.2 and Ni:16.0-39.8 microg metal/kg amended soil, compared
      with Zn:16.4-41.1, Cu:6.2-25.3, Pb:16.9-41.7, and Ni:3.7-25.4 microg metal/kg
      soil from the control soils. Losses of Zn, Cu, Pb and Ni from fresh MADD cake
      amended soils (19.8-41.3, 3.2-25.8, 21.6-51.6 and 7.6-36.5 microg metal/kg
      amended soil, respectively) and from dry MADD cake amended soils (10.7-36.7, 1.8
      23.8, 21.2-51.2 and 6.8-39.2 microg metal/kg amended soil, respectively) were
      similar to the controls. Generally, quantities of metals leached followed the
      order Zn = Pb > Cu > Ni, which was consistent with the levels of metals in the
      original sludge/soil mixtures. These results suggest that composting or drying
      MADD biosolids is unlikely to increase the risk of groundwater contamination when
      compared to the use of MADD cake; therefore, the changes in UK sludge use in
      agriculture guidelines are satisfactory in this respect.

PMID- 11333038
TI  - Kinetics of inhibition in the biodegradation of monoaromatic hydrocarbons in
      presence of heavy metals.
AB  - The toxicity and inhibitory effects of heavy metals such as cadmium, nickel and
      zinc on alkylbenzene removal were evaluated with a Bacillus strain. The kinetics
      of alkylbenzene biodegradation with the different heavy metals at various
      concentrations were modeled using the Andrews equation which yielded a good fit
      between model and experimental data. Additional experiments undertaken with a
      Pseudomonas sp. in presence of nickel confirmed a good fit between experimental
      data and the Andrews model for this strain as well. The heavy metals inhibition
      constants (Ki) were calculated for different combinations of volatile organic
      compounds (VOC) and heavy metals. The present approach provides a method for
      evaluating and quantifying the inhibition effect of heavy metals on the
      biodegradtion of pollutants by specific microbial strains.

PMID- 11333039
TI  - Obtaining a protein concentrate from integral defatted sunflower flour.
AB  - Proteins which are found in integral defatted sunflower flour (27% of protein in
      dry weight) allow us to produce a protein concentrate by means of extraction of
      proteins with a basic pH solution, followed by their precipitation with an acid
      pH solution. Once the suitable conditions for pH and temperature were fixed in
      order to carry out these processes, a solid proteic concentrate (71% of protein
      in dry weight) was obtained which was rich in glutamic and aspartic acids, with a
      liquid supernatant very rich in phosphorus and potassium, which might be used as
      an agricultural fertilizer.

PMID- 11333040
TI  - Effects of supplemental methionine and lysine on the nutritional value of
      housefly larvae meal (Musca domestica) fed to rats.
AB  - The performance and blood composition of rats fed housefly larvae meal
      supplemented with, or without, methionine and lysine, or fed at high
      concentration were investigated. Rats fed supplemental methionine alone achieved
      highest body weight gain (P < 0.05). Dietary supplementation of both methionine
      and lysine or high dietary concentration of larvae meal depressed (P < 0.05) rat
      feed intake. The blood composition of rats was superior (P < 0.05) on methionine
      supplemented larvae meal. Additional amino acids from larvae elicited higher (P <
      0.05) serum proteins, cholesterol and triglyceride; however, other blood
      biochemical profiles were lower (P < 0.05) than in the unsupplemented group. In
      conclusion, housefly larvae meal seemed deficient in methionine and it benefited
      the rat tremendously to supplement with this amino acid: however, additional
      lysine and high dietary inclusion of larvae meal as sole protein source appeared
      nutritionally inconsequential.

PMID- 11333041
TI  - The application of kudzu as a medium for the adsorption of heavy metals from
      dilute aqueous wastestreams.
AB  - This study assessed the use of kudzu (Pueraria lobata ohwi) as a medium for the
      capture of copper, cadmium, and zinc from low concentration solutions. The rate
      and extent of uptake was studied using a system of standardized batch adsorbers
      under steady-state and transient-rate conditions. All plant components were
      tested. Residual metals analyses were performed on an ICP-AES/OES (Optima 3000
      DV). The Langmuir, Freundlich, and Redlich-Peterson isotherms were determined;
      the Langmuir isotherm was found to best represent the data for copper and cadmium
      uptake. The Redlich-Peterson best represented the data for zinc. Kudzu was
      determined to be an effective adsorbent for removal of heavy metals. Though its
      capacity for metals removal is less than commercial grade ion exchange resins, it
      could be used at much lower cost, and may find application in the treatment of
      dilute mixed-matrix metal wastestreams, such as urban runoff, where the
      application of resins would be expensive and subject to premature poisoning by
      interfering contaminants.

PMID- 11333042
TI  - Preparation of activated carbons from corn cob catalyzed by potassium salts and
      subsequent gasification with CO2.
AB  - In the present study, granular activated carbons were prepared from agricultural
      waste corn cob by chemical activation with potassium salts and/or physical
      activation with CO2. Under the experimental conditions investigated, potassium
      hydroxide (KOH) and potassium carbonate (K2CO3) were effective activating agents
      for chemical activation during a ramping period of 10 degrees C/min and
      subsequent gasification (i.e., physical activation) at a soaking period of 800
      degrees C. Large BET surface areas (>1,600 m2/g) of activated carbons were thus
      obtained by the combined activation. In addition, this study clearly showed that
      the porosity created in the acid-unwashed carbon products is substantially lower
      than that of acid-washed carbon products due to potassium salts left in the pore
      structure.

PMID- 11333043
TI  - Biotransformation of cholesterol using Lactobacillus bulgaricus in a glucose
      controlled bioreactor.
AB  - A novel single-step microbial transformation process for the production of
      testosterone from cholestrol by Lactobacillus bulgaricus in an aerated fermenter
      was investigated. The metabolism of glucose possibly supplying reducing power as
      NADH was necessary for the reduction of androst-4-en-3,17-dione (AD) to
      testosterone (TS). The growth period for the accumulation of testosterone in
      maximal amount and the residual glucose increased in parallel with the amount of
      glucose supplement in growth cultures. After the glucose in the fermentation
      culture was completely exhausted, most of the testosterone was oxidized to AD.
      Addition of a larger amount of glucose could prevent oxidation of testosterone to
      AD. The biotransformation of cholestrol was significantly increased in the
      presence of cyclodextrin (CD) in the fermenting medium. The addition of 0.1% CD
      to the growth medium facilitated the transport of the steroid substrate through
      the microbial cell wall.

PMID- 11333044
TI  - Enhancement of the thermophilic stage in cattle waste composting by addition of
      tofu residue.
AB  - The microbial degradation and temperature rise during the composting of a cattle
      waste and rice straw mixture blended with tofu (soybean curd) residue was
      investigated using an insulated and unheated in-vessel composter (effective
      volume, 12 1) and a static pile with passive aeration. The addition of 11% (dry
      weight basis) of tofu residue shortened the time required for temperature to
      reach the thermophilic phase and increased the duration of the temperatures above
      55 degrees C significantly, but the maximum temperature was not affected by the
      additive level. As shown by the change in BOD, most of the easily biodegradable
      matter in the tofu residue was consumed during 12 days of composting. The same
      results were observed in the temperature profile of the static pile with passive
      aeration. Tofu residue addition yielded a higher maximum temperature and a nearly
      two times longer duration of temperatures above 55 degrees C in almost all
      locations of the pile. The use of tofu residue as a co-composting material would
      promote thermophilic degradation throughout the entire composting mass.

PMID- 11333045
TI  - The adsorption of Congo red and vacuum pump oil by rice hull ash.
AB  - Rice hull ash (RHA) of large surface area was obtained by acid wash and then
      calcination at 600 degrees C for 4 h. The white ash was then mixed with kaolin
      and starch to make pellet adsorbents with reasonable strength to be utilized in a
      packed column. Both ash and pellet samples showed good adsorption capacities
      toward the organic substances in wastewater. Furthermore, the surface nature of
      the white ash and pellet adsorbent could be modified through either hydration or
      esterification reactions. Corresponding changes in silanol concentrations were
      successfully correlated to changes in adsorption capacity toward either Congo red
      or vacuum pump oil molecules.

PMID- 11333046
TI  - Further evidence of localized posterior interatrial conduction delay in lone
      paroxysmal atrial fibrillation.
AB  - AIMS: Prolongation of interatrial conduction time has been reported in patients
      with paroxysmal atrial fibrillation (PAF). The study objective was to localize
      the region of the conduction delay in patients with lone PAF. METHODS AND
      RESULTS: Twenty-one patients with lone PAF and 23 patients with AV nodal re
      entrant tachycardia ablation without history of PAF (control group) were
      recruited. Endocardial recordings were made during sinus rhythm and programmed
      atrial stimulation. The authors measured the interatrial conduction time, the
      'right-sided' conduction time between the high lateral right atrium and the
      proximal coronary sinus (RA-CSp), and the 'left-sided' conduction time between
      the proximal and the distal coronary sinus (CSp-LA). During sinus rhythm, the
      interatrial conduction time was longer in the PAF group (103 +/- 19 vs 86 +/- 12
      ms, P<0.01) due to delay of right-sided conduction (RA-CSp was 74 +/- 20 vs 56 +/
      10 ms, P<0.01). During programmed stimulation at the distal coronary sinus, the
      maximal RA-CSp time was also longer in the PAF group (110 +/- 47 vs 69 +/- 16 ms,
      P<0.05). No differences in CSp-LA time were observed. CONCLUSION: This study
      supports the role of posterior septal right atrial conduction disturbances in the
      genesis of lone PAF.

PMID- 11333047
TI  - Atrial arrhythmia suppression by atrial overdrive pacing: pacemaker Holter
      assessment.
AB  - The purpose of this study was to assess the efficacy of overdrive, single-site
      right atrial appendage pacing to reduce the burden of atrial fibrillation (AF)
      when compared with a standard lower rate limit of 60 bpm. This was verified by
      using the pacemaker's Holter. Eighteen subjects with a pre-implant history of
      paroxysmal AF and implanted DDDR mode-switching pacemakers were recruited. The
      pacemaker lower rate limit was programmed in random order to 60, 75 or 90 bpm for
      three 2-month periods and the amount of AF quantified. In addition, the exercise
      tolerance (ET), general well being (GWB), functional capacity (FC) and specific
      symptom prevalence (SSP) were assessed. The main finding of the study was that
      when ranked according to the amount of AF, there was no significant difference in
      the amount of AF according to the pacing rate. Six patients failed to tolerate
      pacing at 90 bpm. There were no differences in the ET, GWB, FC and SSP scores. It
      is concluded that those clinicians that manage patients with paroxysmal

PMID- 11333048
TI  - Ventricular tachycardia with QRS configuration similar to that in sinus rhythm
      and a myocardial origin: differential diagnosis with bundle branch reentry.
AB  - INTRODUCTION: Tachycardia with a QRS configuration which resembles that in sinus
      rhythm is usually thought to be supraventricular. Ventricular tachycardia, with a
      similar QRS configuration to that in sinus rhythm on the 12-lead ECG, can occur.
      The mechanisms of this form of ventricular tachycardia have not been previously
      reported. METHODS AND RESULTS: The mechanism of ventricular tachycardia was
      defined during electrophysiological study in five patients. During sinus rhythm,
      all patients had a wide QRS complex (>0.12 s) on the 12-lead ECG. The morphology
      remained grossly unchanged during spontaneous, symptomatic tachycardia. Four of
      the five patients had coronary artery disease and left ventricular dysfunction.
      The remaining patient had idiopathic dilated cardiomyopathy. The relationship
      between the His bundle, deflection, the right bundle branch and the QRS complex
      was evaluated during tachycardia. Atrial and ventricular pacing, and ventricular
      activation mapping were performed during tachycardia to define the tachycardia
      mechanism. The tachycardia induced at electrophysiological testing, which was
      similar to the clinical tachycardia, was proven to be ventricular tachycardia in
      each patient. The morphology of ventricular tachycardia was right bundle branch
      block in two patients and left bundle branch block in three patients. The median
      tachycardia cycle length was 300 ms (range: 260-480 ms). His bundle activation
      occurred in a 1:1 relationship with ventricular activation during tachycardia in
      all patients at least intermittently. The tachycardias were thought initially to
      be bundle branch reentry tachycardia. With further intervention and continued
      observation, it became clear that His bundle activation was passive and was not
      required for the tachycardia to sustain. During tachycardia, His bundle
      activation appeared to precede the local ventricular activation. Instead, the His
      bundle was activated slowly from the previous ventricular beat causing a long
      ventricular-His (VH) interval. This was shown by: (1) activation patterns, (2)
      response to pacing, (3) intermittent VH dissociation, and (4) termination of
      ventricular tachycardia. CONCLUSION: A unique form of ventricular tachycardia is
      described. The QRS complex morphology on the 12-lead ECG during tachycardia was
      grossly similar to that during sinus rhythm. The His bundle activation was
      passive and occurred with a long activation time from the ventricle to the His
      bundle. Although it mimics usual bundle branch reentry, this form of ventricular
      tachycardia appears to be due to a different mechanism in which the His bundle is
      not obligatory for the continuation of the reentrant phenomenon.

PMID- 11333049
TI  - Validation by serial standardized testing of a new rate-responsive pacemaker
      sensor based on variations in myocardial contractility.
AB  - AIMS: Preliminary studies have shown that peak endocardial acceleration (PEA),
      measured by a micro-accelerometer at the right ventricular apex, is highly
      correlated with left ventricular contractility (dp/dt max). Furthermore, changes
      in PEA are closely correlated with sinus node rate changes during exercise and
      during pharmacological interventions. Peak endocardial acceleration has,
      therefore, been used to drive a rate-responsive DDD pacemaker. This study
      compared the chronotropic performance of such devices implanted in 14 patients
      suffering from chronotropic incompetence with that observed in 18 control
      subjects in normal sinus rhythm. METHODS AND RESULTS: Five standardized daily
      life activities (hall walk, climbing up and down stairs, squatting and
      hyperventilation) and two types of exercise (Bruce treadmill protocol and bicycle
      ergometry) were performed in a random order after individual programming of each
      pacemaker. For each test, a correlation coefficient was calculated between
      changes in PEA and variations in paced rate, between instantaneous variations in
      heart rate monitored by telemetry and continuous measurement of heart rate by the
      pacemaker, and between sensor-driven rate in patients and normal sinus rhythm in
      controls. The variations in paced heart rate were closely correlated with those
      observed in subjects with normal sinus rhythm, and proved to be sensitive,
      specific, rapid and independent of the type of exercise. After optimal
      programming of the sensor, PEA modulates the heart rate as expected during normal
      sinus rhythm. CONCLUSIONS: In this study, a single PEA sensor successfully
      restored chronotropic response in a population of paced patients with severe
      chronotropic incompetence. Peak endocardial acceleration can be monitored on a
      beat-to-beat basis, in parallel with heart rate, and the pacemaker can be
      accurately programmed with a single exercise test.

PMID- 11333050
TI  - Indications for dual-chamber cardioverter defibrillators at implant and at 1 year
      follow-up: a retrospective analysis in the single-chamber defibrillator era.
AB  - AIM: This retrospective four-centre study assessed the current indications for
      dual-chamber implantable cardioverter defibrillators (ICDs) at implant and during
      a medium-term follow-up period in a group of patients treated by single-chamber
      ICD in the pre dual-chamber ICD era. METHODS AND RESULTS: The study population
      consisted of 153 consecutive patients (127 males, mean age 58 +/- 6 years)
      treated by single-chamber ICD for ventricular tachycardia and/or ventricular
      fibrillation. Definite indications for having a dual-chamber ICD included the
      presence of sinus node dysfunction and of second- or third-degree
      atrioventricular (AV) block, while possible indications were represented by
      paroxysmal atrial fibrillation or flutter and first-degree AV block. At implant,
      dual-chamber ICD would appear definitely indicated in 10.5% of cases, and
      possibly indicated in an additional 17.5% of cases. During 12 +/- 10 months
      follow-up, such percentages remained stable (11 and 19.5%, respectively).
      Inappropriate ICD intervention was documented in five of 13 patients (38%), with
      episodes of paroxysmal atrial fibrillation or flutter. CONCLUSION: In this non
      selected study population, a dual-chamber ICD would have potentially benefited
      approximately 30% of the patients. During medium-term follow-up, there was no
      progression towards increasing dual-chamber ICD indications. The 15% cumulative
      incidence of paroxysmal atrial tachyarrhythmias justifies the activation of
      dedicated detection algorithms.

PMID- 11333051
TI  - Age and gender differences in basal and isoprenaline protocols for head-up tilt
      table testing.
AB  - AIMS: Syncope is a common occurrence, the prevalence of which increases with age,
      and among the multiple causes of syncope, neurally mediated syncope is thought to
      be a frequent cause in the young and in the elderly. Head-up tilt table testing
      (HUT) has become the diagnostic test of choice for neurally mediated syncope, the
      response to which varies clearly with age. The purpose of this study is to report
      the differences among patients suffering syncope referred for HUT, and the
      influence of age and gender on HUT results (percentage of positive responses and
      response patterns) in two study protocols (basal and isoprenaline). METHODS AND
      RESULTS: One thousand, two hundred and nineteen patients with syncope were
      referred to the authors' Cardiology Department for HUT from September 1990 to
      April 2000; 1061 undergoing basal HUT (Group A) and 158 undergoing isoprenaline
      tilt table testing (Group B). Complications were noted in neither protocol.
      Females were more frequent among young people, and males in the elderly (P<0.05).
      Head-up tilt table testing was abnormal in 259 (24.4%) patients in Group A and in
      85 (53.7%) patients in Group B (P<0.05), and no gender differences were observed.
      The positive rate of tests in men and women significantly declined with age in
      Group A (P<0.05), but not in Group B (P=ns). There were no differences in the
      patterns of haemodynamic collapse in both groups. CONCLUSIONS: In the study of
      syncope, basal HUT has a high positive rate in young people; a decrease in
      positive rate with age suggests, however, the need for using another protocol
      with a similar diagnostic accuracy in the elderly.

PMID- 11333052
TI  - Clinical characteristics of patients with vasovagal reactions presenting as
      unexplained syncope.
AB  - OBJECTIVE: To describe the clinical characteristics of vasovagal syncope (VVS) in
      patients presenting to a tertiary referral centre with unexplained syncope, in
      whom the diagnosis of VVS was confirmed by tilt table testing (HUT) and in whom
      other causes of syncope excluded. DESIGN: Prospective study of 62 consecutive
      patients with more than two episodes of syncope in the past year. SETTING: A
      regional tertiary referral centre for patients with unexplained syncope.
      PATIENTS: Sixty-two patients, mean age 50 +/- 21 years, 39 female, were studied.
      Mean duration of symptoms was 5 years. Average frequency of attacks was one
      episode per week. INTERVENTIONS: Detailed semi-structured questionnaires were
      completed regarding presenting symptoms. RESULTS: In over one-third of patients,
      episodes occurred suddenly, with no prodromal features. In those with prodrome,
      71% had autonomic symptoms, but 27% had palpitations or dyspnoea and 21% had
      chest pain. Eleven percent of patients denied known provocative features. In the
      remainder, the most common were prolonged standing (37%), hot weather (27%) and
      lack of food (23%). One-fifth had symptoms sitting and 5% whilst driving. Seventy
      five percent of patients suffered after effects, the most common being severe
      fatigue. Over half sustained an injury during syncope, and 13% sustained a
      fracture. Unwitnessed episodes occurred in 25%. Pallor was reported in half the
      cases, sweating in 13% and myoclonus in 5%. CONCLUSIONS: Atypical presentations
      of VVS occur in many patients referred to a tertiary referral centre. Knowledge
      of the clinical characteristics of unexplained syncope for which VVS is the
      attributable diagnosis should assist in appropriate management of such patients.

PMID- 11333053
TI  - Wide QRS complex tachycardia during radiofrequency ablation of a concealed
      accessory pathway: what is the tachycardia mechanism?

PMID- 11333054
TI  - A novel use of cardiac pacing to improve cardiac function in patients with heart
      failure and permanent atrial fibrillation.

PMID- 11333056
TI  - The yet unresolved dilemma of syncope in Brugada syndrome.

PMID- 11333055
TI  - An assessment of the optimal ventricular pacing site in patients undergoing
      'ablate and pace' therapy for permanent atrial fibrillation.

PMID- 11333057
TI  - Syncope in pharmacologically unmasked Brugada syndrome: indication for an
      implantable defibrillator or an unresolved dilemma?
AB  - A 30-year-old Caucasian male was referred for evaluation of a 2-year history of
      recurrent post-exertion lightheadedness and near syncopal spells in the setting
      of a family history of unexplained sudden cardiac death. Cardiac evaluation
      demonstrated normal heart structure, but the 12-lead surface ECG was suggestive
      of but not diagnostic of Brugada syndrome. An exercise stress test reproduced the
      patient's usual symptoms during the recovery period, and was consistent with a
      typical vasovagal faint. The same symptoms were observed during a head-up tilt
      table test. However, given the family history and ECG, pharmacological testing
      with procainamide, isoprenaline and metoprolol, as well as programmed ventricular
      stimulation, were undertaken. Pharmacological provocation further supported a
      diagnosis of Brugada syndrome, whereas programmed ventricular stimulation was
      considered non-diagnostic regarding ventricular tachyarrhythmia susceptibility.
      Consequently, despite ECG and pharmacological findings suggestive of Brugada
      syndrome, there appeared to be sufficient evidence to believe that this patient's
      symptoms were the result of neurally mediated syncope and not due to ventricular
      tachyarrhythmias. The patient was treated with midodrine, and has remained
      symptom-free for 16 months. Thus, given the frequency with which vasovagal
      syncope occurs in young patients, its occurrence is not unexpected in individuals
      with concomitant diagnoses such as Brugada syndrome. In as much as current
      recommendations favour implantable defibrillators in symptomatic Brugada
      syndrome, the identification of other causes of syncope in such patients poses an
      uncomfortable, and currently unsettled dilemma.

PMID- 11333058
TI  - Catheter ablation of an epicardial accessory pathway via the middle cardiac vein
      guided by monophasic action potential recordings.
AB  - This report describes a case of permanent junctional reciprocating tachycardia
      (PJRT) that was ablated via the middle cardiac vein, guided by monophasic action
      potential recording. The patient was a 63-year-old woman who had been suffering
      from palpitation for 10 years. ECG during palpitation showed a narrow QRS
      tachycardia with a long RP interval. Electrophysiological study revealed that
      this tachycardia was an orthodromic reciprocating tachycardia, via an accessory
      pathway with a decremental property and a long ventriculoatrial interval (130
      ms): PJRT. The earliest atrial activation during tachycardia was detected at the
      junction of the middle cardiac vein with the coronary sinus. Monophasic action
      potentials were recorded to confirm that the ablation catheter was in contact
      with the epicardium.

PMID- 11333059
TI  - Internal cardioversion. Is it needed? How best to perform it.

PMID- 11333060
TI  - Low-energy internal cardioversion in patients with long-lasting atrial
      fibrillation refractory to external electrical cardioversion: results and long
      term follow-up.
AB  - AIM: Low-energy internal cardioversion is a new electrical treatment for patients
      with persistent atrial fibrillation. This paper evaluates the efficacy and safety
      of low-energy internal cardioversion in patients with long-lasting atrial
      fibrillation refractory to external electrical cardioversion, and the clinical
      outcome of such patients. METHOD AND RESULTS: The study population consisted of
      55 patients [32 male, mean age 65 +/- 10 years, 48 (87%) with underlying heart
      disease] with long-lasting (mean 18 +/- 34 months) atrial fibrillation in whom
      external cardioversion had failed to restore sinus rhythm. Two custom-made
      catheters were used: one positioned in the right atrium and one in the coronary
      sinus or the left pulmonary artery. A standard catheter was inserted into the
      right ventricular apex to provide R wave synchronization. Sinus rhythm was
      restored in 52 patients (95%) with a mean defibrillating energy of 6.9 +/- 2.6 J
      (320 +/- 60 V). No complications were observed. During follow-up (mean 18 +/- 9
      months), 16 patients (31%) suffered early recurrence (< or = 1 week) of atrial
      fibrillation and 20 patients (38%) had late recurrence (> 1 week, mean 3.5 +/-
      3.6 months) of atrial fibrillation. Six patients with a late recurrence again
      underwent cardioversion and five of these maintained sinus rhythm. Therefore, a
      total of 21/52 patients (40%) were in sinus rhythm at the end of follow-up. No
      clinical difference was found between patients with and without recurrences.
      CONCLUSIONS: Low-energy internal cardioversion is a useful means of restoring
      sinus rhythm in patients with long-lasting atrial fibrillation refractory to
      external electrical cardioversion. More than one-third of patients maintained
      sinus rhythm during long-term follow-up.

PMID- 11333061
TI  - External cardioversion of atrial fibrillation: comparison of biphasic vs
      monophasic waveform shocks.
AB  - AIMS: It is well established in transthoracic ventricular defibrillation that
      biphasic truncated waveform shocks are associated with superior defibrillation
      efficacy when compared with damped sine wave monophasic waveform shocks. The aim
      of this study was to explore whether biphasic waveform shocks were superior to
      monophasic waveform shocks for external cardioversion of atrial fibrillation
      (AF). METHODS AND RESULTS: Fifty-seven patients in whom cardioversion of AF was
      indicated were randomized in this prospective study, to transthoracic
      cardioversion with either monophasic damped sine waveform shocks or biphasic
      impedance compensating waveform shocks. In the group randomized to monophasic
      waveform shocks (27 patients), a first shock of 150 J was delivered, followed (if
      necessary) by a 360 J shock. In the biphasic waveform group (30 patients), the
      first shock had an energy of 150 J and (if necessary) a second 150 J was
      delivered. All shocks were delivered in the anterolateral chest pad position.
      Sinus rhythm was restored in 16 patients (51%) with the first monophasic shock
      and in 27 patients (86%) with the first biphasic shock. The difference was
      statistically significant (P=0.02). After the second shock, sinus rhythm was
      obtained in a total of 24 patients (88%) with monophasic shocks and in 28
      patients (93%) with biphasic shocks. No complication was observed in either group
      and cardiac enzymes (CK, CKmb, troponin I, myoglobin) did not show any
      significant changes. CONCLUSION: This study suggests that at the same energy
      level of 150 J, biphasic impedance compensating waveform shocks are superior to
      monophasic damped sine waveform shocks cardioversion of atrial fibrillation.

PMID- 11333062
TI  - Prior stimulant treatment in adolescents with bipolar disorder: association with
      age at onset.
AB  - OBJECTIVES: To compare demographic and clinical characteristics between bipolar
      adolescents with and without a history of stimulant treatment, we hypothesized
      that adolescents treated with stimulants would have an earlier age at onset of
      bipolar disorder, independent of co-occurring attention-deficit-hyperactivity
      disorder (ADHD). METHOD: Thirty-four adolescents hospitalized with mania were
      assessed using the Washington University at St Louis Kiddie Schedule for
      Affective Disorders and Schizophrenia (WASH-U-KSADS). We systematically evaluated
      age at onset of bipolar disorder and pharmacological treatment history. RESULTS:
      Bipolar adolescents with a history of stimulant exposure prior to the onset of
      bipolar disorder had an earlier age at onset of bipolar disorder than those
      without prior stimulant exposure. Additionally, bipolar adolescents treated with
      at least two stimulant medications had a younger age at onset compared with those
      who were treated with one stimulant. There was no difference in age at onset of
      bipolar disorder between bipolar adolescents with and without ADHD. CONCLUSIONS:
      Our results suggest that stimulant treatment, independent of ADHD, is associated
      with younger age at onset of bipolar disorder. A behavioral sensitization model
      is proposed to explain our findings. There are several limitations to our study
      including the small sample size, the retrospective assessment of stimulant
      exposure and age at onset of bipolar disorder, and the inclusion of only
      hospitalized patients, who may be more likely to present with a severe illness.
      Nonetheless, future prospective longitudinal investigations that systematically
      assess the effects of stimulant medications in children with or at genetic risk
      for bipolar disorder are warranted.

PMID- 11333063
TI  - Persistent attentional dysfunction in remitted bipolar disorder.
AB  - OBJECTIVES: Although previous research has shown that attentional dysfunction is
      common during acute mood episodes in individuals with bipolar disorder (BPD), few
      studies have examined whether attentional deficits are evident during periods of
      symptom stability. The goal of this study was to determine whether clinically
      stable individuals with BPD would have attentional disturbances relative to
      healthy subjects. METHODS: Fourteen patients with BPD and 12 healthy comparison
      subjects participated in the study, and were administered the Degraded Stimulus
      Continuous Performance Test (DSCPT), Digit Span Distractibility Test (DSDT) and
      Grooved Pegboard Test (GPT). Psychiatric symptoms were assessed with the Young
      Mania Rating Scale and the Scale for the Assessment of Positive Symptoms.
      Medication side effects were measured with the Simpson Rating Scale. RESULTS: The
      patient group responded significantly more slowly than the control group on the
      DSCPT (z = -2.52, p = 0.01) and the GPT (z = -3.37, p = 0.001). There was a trend
      towards the BPD patients demonstrating impaired perceptual sensitivity on the
      DSCPT (z = 1.68, p = 0.09). The two groups did not differ on the DSDT (z = -1.06,
      p = 0.3). Poor performance on the GPT and DSCPT target reaction time were not
      associated with symptom ratings or medications. CONCLUSION: The findings suggest
      that impairments in fine motor skills and reaction time may be present in
      clinically stable patients with BPD, even after accounting for psychiatric
      symptoms and medication effects. Performance decrements on attentional tasks may
      be in part reflective of motor impairments in patients with BPD.

PMID- 11333064
TI  - The prophylactic effect of long-term lithium administration in bipolar patients
      entering treatment in the 1970s and 1980s.
AB  - OBJECTIVES: The aim of the study was to assess the prophylactic effect of long
      term lithium administration in patients with bipolar mood disorders entering
      treatment in the 1970s and 1980s at the outpatient clinic of the Department of
      Psychiatry, University of Medical Sciences, Poznan, Poland. METHODS: The clinical
      characteristics of two groups of patients before and during lithium therapy were
      compared, namely, the 60 bipolar patients who entered lithium prophylaxis in the
      1970s and 49 patients who entered in the 1980s. Both groups received the drug
      over a 10-year period. RESULTS: The patients who entered lithium in the 1970s had
      fewer previous episodes of depression and more of mania than the patients who
      entered the therapy in the 1980s, although the total number of affective episodes
      was similar in both groups. The overall prophylactic efficacy of lithium over a
      10-year period of administration was similar in both groups, except for a trend
      towards a greater number of depressive episodes in the first year of lithium
      prophylaxis in the 1980s group. The excellent lithium responders constituted 35%
      of the 1970s patients and 27% of those in the 1980s group. The 1970s patients
      were maintained on a higher level of serum lithium compared to the patients in
      the 1980s group and had more lithium-induced side effects. CONCLUSIONS: A
      decrease in lithium prophylactic efficacy in consecutive decades was not
      observed. Small differences between the bipolar patients entering lithium therapy
      in the 2 decades were observed in terms of the previous history of illness and
      during the course of lithium administration.

PMID- 11333065
TI  - A pilot study of rapid lithium administration in the treatment of acute mania.
AB  - OBJECTIVES: The use of rapid lithium dosage administration, a strategy that could
      lead to rapid improvement in mania, has been largely unexamined. In this open
      label, pilot, acute-treatment study, we sought to determine the safety and
      tolerability of lithium administered at 20 mg/ kg/day. A secondary aim was to
      provide preliminary data regarding the efficacy of this strategy in ameliorating
      manic, depressive, and psychotic symptoms. METHODS: Fifteen patients hospitalized
      with DSM-IV bipolar disorder, manic or mixed, and who provided written informed
      consent, received lithium 20 mg/kg/day for up to 10 days. Patients were evaluated
      for adverse effects daily. Lithium levels were obtained on days 2, 3, 4, 5, 7,
      and 10 or at study termination. Electrocardiograms (EKGs) were performed at
      baseline and on days 1-5, 7, and 10 or at study termination. Symptomatic
      improvement was assessed daily using the Young Mania Rating Scale, 24-item
      Hamilton Depression Rating Scale, and the Scale for Assessment of Positive
      Symptoms (SAPS). RESULTS: Five of the 15 patients completed the 10-day study
      period. Two patients dropped out due to adverse events. Seven patients did not
      complete the inpatient trial because of improvement sufficient to allow hospital
      discharge. All patients achieved serum lithium concentrations > or =0.6 mEq/L
      after 1 day of treatment; the mean + SD concentration on day 5 was 1.1 (+/- 0.1)
      mEq/L on day 5. There were significant reductions from baseline to endpoint on
      all rating scales, except the SAPS bizarre behavior subscale. CONCLUSIONS: These
      pilot data suggest that lithium 20 mg/kg/day was well tolerated and that this
      strategy may produce rapid improvement in affective and psychotic symptoms. These
      impressions require confirmation in double-blind, randomized trials.

PMID- 11333066
TI  - Family environment of children and adolescents with bipolar parents.
AB  - OBJECTIVES: The effect of family environment on the development of bipolar
      disorder (BD) in children is not known. We sought to characterize families with
      children at high risk for developing BD in order to better understand the
      contributions of family environment to the development of childhood BD. METHODS:
      We collected demographic data and parental ratings on the Family Environment
      Scale (FES) for 56 children (aged 6-18 years) from 36 families with at least one
      biological parent with BD. The cohort had previously been psychiatrically
      diagnosed according to semistructured interviews. RESULTS: Statistical
      comparisons with normative data indicated that parents' ratings were
      significantly lower on the FES Cohesion and Organization scales and were
      significantly higher on the FES Conflict scale. Multivariate analyses of variance
      indicated that families with both parents having a mood disorder had no
      significantly different FES scores than families with only one parent with a mood
      disorder (BD). Diagnostic data indicated that while 54% of the children in the
      sample had an Axis I disorder and 14% had BD, FES scores did not differ
      significantly for subjects with or without an Axis I disorder, or with or without
      BD. CONCLUSIONS: Families with a bipolar parent differ from the average family in
      having less cohesion and organization, and more conflict. Despite this
      difference, it does not appear that the environment alone of families with a
      bipolar parent determines the outcome of psychopathology in the children, or that
      the psychopathology of the children determines the family environment.

PMID- 11333067
TI  - Electrophysiological and cognitive function in young euthymic patients with
      bipolar affective disorder.
AB  - OBJECTIVES: EEG abnormalities and neurocognitive deficits have been reported in
      patients with bipolar affective disorder. The aim of this study was to ascertain
      whether brain function remains impaired in young bipolar patients who have become
      euthymic in response to treatment. METHODS: Brain function was assessed by
      quantitative electroencephalographic (EEG) power-spectral mapping and by a
      battery of neuropsychological tests. The subjects were 29 euthymic bipolar
      patients aged 18-40 years and 26 healthy volunteers of similar age, IQ and
      socioeconomic status. RESULTS: Grand means of spectral power of the resting EEG
      showed significantly (from p < 0.01 to p < 0.0001) greater power in all wave
      bands (delta, theta, alpha and beta) in patients compared with controls. The most
      marked increases were in right temporal theta and left occipital beta power (with
      eyes open) encompassing brain areas concerned in visuospatial processing.
      Neurocognitive performance was significantly impaired in the patients compared
      with controls in a range of visuospatial tasks. CONCLUSIONS: The findings show
      significant disturbance of EEG activity and deficits in visuospatial processing
      in young bipolar patients despite clinical euthymia. The abnormalities were not
      related to age of onset or duration of illness and do not appear to be
      attributable to medication. The cognitive impairments were associated with the
      number of previous affective episodes.

PMID- 11333068
TI  - Neuropsychological frontal lobe tests indicate that bipolar depressed patients
      are more impaired than unipolar.
AB  - OBJECTIVES: The aim of this study was to compare the neuropsychological
      performance of patients with bipolar or unipolar mood disorders during acute
      episodes of depression using intelligence and frontal lobe tests. METHODS:
      Fifteen patients with bipolar depression (BP) and 30 with unipolar depression
      (UP) were studied. For the neuropsychological assessment, the following tests:
      the Wechsler Adult Intelligence Scale-Revised (WAIS-R), the Trail Making Test
      (TMT), the Stroop test, the verbal fluency test and the Wisconsin Card Sorting
      Test (WCST) were used. RESULTS: The mean intensity of depression and mean
      duration of illness were similar in both groups. Patients in the BP group
      achieved significantly lower levels of performance in the non-verbal part of WAIS
      R, in both parts of the Stroop test, in the verbal fluency test and also showed a
      tendency to achieve poorer results in TMT-B than those in the UP group. Bipolar
      depressed patients also produced significantly poorer results with the WCST as
      they made twice as many perseverative errors and only completed half of the
      correct categories compared with the UP patients. The results of the TMT-A tests,
      which measure psychomotor slowness, were similar in BP and UP patients. No
      differences between the results of male and female patients were noted in either
      group. Deterioration of the results associated with duration of the illness was
      only observed in the UP patients. CONCLUSIONS: A higher degree of cognitive
      dysfunction connected with frontal lobe activity during an acute depressive
      episode was found in bipolar compared with unipolar depressed patients. These
      results may corroborate other findings pointing to pathogenic distinctions
      between bipolar and unipolar affective illness and to some similarities between
      bipolar illness and schizophrenia.

PMID- 11333069
TI  - ECT in bipolar and unipolar depression: differences in speed of response.
AB  - OBJECTIVES: There is sparse evidence for differences in response to
      electroconvulsive therapy (ECT) between patients with bipolar or unipolar major
      depression, with virtually no information on speed of response. We contrasted a
      large sample of bipolar (BP) and unipolar (UP) depressed patients in likelihood
      and rapidity of clinical improvement with ECT. METHODS: Over three double-blind
      treatment protocols, 228 patients met Research Diagnostic Criteria for UP (n =
      162) or BP depression (n = 66). Other than lorazepam PRN (3 mg/day), patients
      were withdrawn from psychotropics prior to the ECT course and until after post
      ECT assessments. Patients were randomized to ECT conditions that differed in
      electrode placement and stimulus intensity. Symptomatic change was evaluated at
      least twice weekly by a blinded evaluation team, which also determined treatment
      length. RESULTS: Patients with BP and UP depression did not differ in rates of
      response or remission following the ECT course, or in response to unilateral or
      bilateral ECT. Degree of improvement in Hamilton Rating Scale for Depression
      scores following completion of ECT was also comparable. However, BP patients
      received significantly fewer ECT treatments than UP patients, and this effect was
      especially marked among bipolar ECT responders. Both BP I and BP II patients
      showed especially rapid response to ECT. CONCLUSIONS: The BP/UP distinction had
      no predictive value in determining ECT outcome. In contrast, there was a large
      effect for BP patients to show more rapid clinical improvement and require fewer
      treatments than unipolar patients. The reasons for this difference are unknown,
      but could reflect a more rapid build up of anticonvulsant effects in BP patients.

PMID- 11333071
TI  - The role of person familiarity in young infants' perception of emotional
      expressions.
AB  - This research investigated the role of person familiarity in the ability of 3.5
      month-old infants to recognize emotional expressions. Infants (N = 72) were
      presented simultaneously with two filmed facial expressions, happy and sad,
      accompanied by a single vocal expression that was concordant with one of the two
      facial expressions. Infants' looking preferences and facial expressions were
      coded. Results indicated that when the emotional expressions were portrayed by
      each infant's own mother, infants looked significantly longer toward the facial
      expressions that were accompanied by affectively matching vocal expressions.
      Infants who were presented with emotional expressions of an unfamiliar woman did
      not. Even when a brief delay was inserted between the presentation of facial and
      vocal expressions, infants who were presented with emotional expressions of their
      own mothers looked longer at the facial expression that was sound specified,
      indicating that some factor other than temporal synchrony guided their looking
      preferences. When infants viewed the films of their own mothers, they were more
      interactive and expressed more positive and less negative affect. Moreover,
      infants produced a greater number of full and bright smiles when the sound
      specified emotion was "happy," and particularly when they viewed the happy
      expressions of their own mothers. The average duration of negative affect was
      significantly longer for infants who observed the unfamiliar woman than for those
      who observed their own mothers. These results show that when more contextual
      information-that is, person familiarity-was available, infants as young as 3.5
      months of age recognized happy and sad expressions. These findings suggest that
      in the early stages of development, infants are sensitive to contextual
      information that potentially facilitates some of the meaning of others' emotional
      expressions.

PMID- 11333070
TI  - Modifying the distribution of attention in infants.
AB  - In three experiments, the distribution and malleability of infant visual
      attention were studied in 5-month-olds (N = 72) while they inspected large
      geometric designs. In Experiment 1, we established that infants maintained their
      distribution of attention from a pretest to a familiarization phase. We also
      replicated and extended our previous findings that infants who examined targets
      with briefer, more numerous looks and shifts-short lookers-had novelty scores
      above chance, whereas long lookers demonstrated chance responding. In Experiment
      2, different portions of the display were successively illuminated with red
      light. This manipulation induced long lookers to scan like short lookers during
      familiarization; they then showed novelty scores well above chance. A third
      experiment ruled out the simple presence of a red light as the source of this
      effect. In sum, then, these results suggest that the distribution of attention is
      malleable, and that a broader distribution of attention, as reflected in briefer
      and more numerous looks and shifts, can improve processing.

PMID- 11333072
TI  - The development of memory for location: what role do spatial prototypes play?
AB  - Two experiments investigated the role of spatial prototypes in estimates of
      location. In Experiment 1 (N = 144), children and adults learned the locations of
      20 objects in an open, square box designed to look like a model house. In two
      conditions, opaque lines or walls divided the house into four regions, and in the
      other condition, no boundaries were present. Following learning, the dots marking
      the locations were removed, and participants attempted to replace the objects.
      Children and adults overestimated distances between target locations in different
      regions. Contrary to Huttenlocher, Hedges, and Duncan's hierarchical theory of
      spatial memory, none of the groups displaced the objects toward the region
      centers. In Experiment 2 (N = 96), boundaries were removed during testing to
      determine whether children and adults were more likely to displace objects toward
      region centers when uncertainty about location increased. Again, all age groups
      overestimated distances between target objects in different regions. In addition,
      adults and 11-year-olds in the most salient boundary condition displaced objects
      toward the region centers. Discussion focuses on the implications of these
      results for understanding how children and adults estimate location.

PMID- 11333073
TI  - Dynamic patterns of time use in adolescence.
AB  - Patterns of time use are tangible representations of individual identity and the
      meaning of age groups in the life course. How do young people allocate their time
      to multiple domains of involvement, including the school, workplace, family, and
      peer group? Drawing on longitudinal data from the Youth Development Study (N =
      1,010), a person-centered analytic strategy was used to describe configurations
      of time use through the high school years. Over half of the students were engaged
      in many domains, although a substantial percentage of students focused their time
      on one or two domains outside the school. Students who were highly engaged in
      multiple domains tended to remain so across grade levels, whereas students
      focused on one or two domains frequently changed their commitments. Plans for
      school, grade point average, future orientations that emphasize marriage and good
      citizenship, and gender significantly predicted time-use patterns. These findings
      elucidate connections among school, work, and other contexts through the high
      school years.

PMID- 11333074
TI  - Infant reactivity and reliance on mother during emotion challenges: prediction of
      cognition and language skills in a low-income sample.
AB  - This investigation considers the association between patterns of emotional
      reactivity and reliance on mother in infancy and cognitive and language
      developments at age 2. Low-income women (N = 518) and their firstborn infants
      participated in (1) a lab-based assessment where emotion challenges were
      presented when the infants were 6 to 9 months old, and (2) an assessment of
      language and cognitive skills at age 2. After controlling for birthweight, early
      sensorimotor delay, and age at testing, infants who displayed a pattern of
      combined high reactivity and high reliance on mother in response to positive,
      anger, and fear emotion challenges had higher cognitive and language skills at
      age 2 compared with infants who displayed patterns of low reactivity and low
      reliance on mother. Children who showed high fearful distress and low reliance on
      mother and whose mothers had low psychological resources had especially poor
      developmental outcomes. The role of maternal availability in the socialization of
      emotion and early communication is discussed.

PMID- 11333075
TI  - Learning words through overhearing.
AB  - Recent research indicates that toddlers can monitor others' conversations,
      raising the possibility that they can acquire vocabulary in this way. Three
      studies examined 2-year-olds' (N = 88) ability to learn novel words when
      overhearing these words used by others. Children aged 2,6 were equally good at
      learning novel words-both object labels and action verbs-when they were
      overhearers as when they were directly addressed. For younger 2-year-olds (2,1),
      this was true for object labels, but the results were less clear for verbs. The
      findings demonstrate that 2-year-olds can acquire novel words from overheard
      speech, and highlight the active role played by toddlers in vocabulary
      acquisition.

PMID- 11333076
TI  - Learning from other people's mistakes: causal understanding in learning to use a
      tool.
AB  - Despite considerable debate about whether nonhuman primates learn to use tools
      via imitation, this type of learning by children has received surprisingly little
      attention. The findings of two studies that go some way toward filling this gap
      are reported here. Study 1 showed that when 2- and 3-year-old children (N = 68)
      were shown a correct solution to a tool-using task (which they could not solve
      spontaneously), all the children in both age groups managed at least a partial
      solution. When children were shown an incorrect solution followed by a correct
      solution, 2-year-olds again produced only a partial solution. By contrast, most 3
      year-olds produced a full solution. Study 2 replicated this age change in a
      separate sample of children (N = 100) with a different tool-using task. Study 2
      also showed that 3-year-olds benefit from observing an incorrect action when it
      can be contrasted with a correct action: they chose the more effective of the two
      actions. Taken together, the two studies indicate that by 3 years of age,
      children do not indiscriminately imitate actions on a tool, but selectively
      reproduce those actions that have a desired causal effect.

PMID- 11333077
TI  - Children's understanding of psychogenic bodily reactions.
AB  - One hundred twenty-eight children in preschool through fifth grade (range = 4,3
      11,4) and 76 adults serving as a comparison group participated in two studies
      that examined how children reason about psychogenic bodily reactions, that is,
      ailments or nonconscious physiological responses with origins in the mind (e.g.,
      stress-induced headache). Psychogenic bodily reactions provide an opportunity to
      study how children integrate knowledge between the domains of bodily response and
      psychology. In Study 1, participants were asked whether various familiar
      psychogenic bodily reactions were possible (e.g., can someone get a tummyache
      from worrying?). In Study 2, participants were presented with a novel domain
      (hypothetical "aliens" from outer space) and were asked whether various
      unfamiliar bodily conditions (e.g., toes swelling) could arise from various
      physical or psychological causes. As predicted, adults typically reported that
      psychogenic bodily reactions were possible, and that unfamiliar bodily conditions
      could result from either psychological or physical causes. In contrast, young
      children typically denied that psychogenic bodily reactions could occur and
      predicted that unfamiliar bodily conditions resulted from physical causes only.
      The results support a developmental path: younger children view psychogenic
      bodily responses as wholly physical, but with age, view them as both physical and
      psychological phenomena.

PMID- 11333078
TI  - The development of an intuitive understanding of entropy.
AB  - Previous studies of the concept of entropy have indicated that before 7 to 9
      years of age, children have difficulty understanding the effects of randomizing
      forces and often predict highly improbable events, such as a return to the
      original ordered state. In the present research, 306 children between 3 and 11
      years of age were asked directly whether undifferentiated forces, such as the
      wind or objects being thrown into the air, could create order or disorder in a
      set of objects. The results showed that even 4-year-olds are sensitive to the
      asymmetrical effects of such events. Older children apply this principle more
      consistently and are able to use it in explaining their answers.

PMID- 11333079
TI  - Emotional development in children with different attachment histories: the first
      three years.
AB  - The development of fear, anger, and joy was examined in 112 children using a
      longitudinal design. Children were observed at 9, 14, 22, and 33 months in
      standard laboratory episodes designed to elicit fear, anger, or joy. At 14
      months, mother-child attachment was assessed in the Strange Situation. The
      attachment groups (avoidant, secure, resistant, and disorganized/unclassifiable)
      differed in the trajectories of emotional development, with the differences first
      apparent at 14 months of age. Resistant children were the most fearful and least
      joyful, and fear was their strongest emotion. More than secure children, they
      responded with distress even in episodes designed to elicit joy. When examined
      longitudinally, over the second and third years, secure children became
      significantly less angry. In contrast, insecure children's negative emotions
      increased: Avoidant children became more fearful, resistant children became less
      joyful, and disorganized/unclassifiable children became more angry. Higher
      attachment security uniquely predicted that at 33 months, children would show
      less fear and anger in episodes designed to elicit fear and anger, and less
      distress in episodes designed to elicit joy, even in conservative regression
      analyses controlling for all the earlier emotion scores.

PMID- 11333080
TI  - "I got some swords and you're dead!": violent fantasy, antisocial behavior,
      friendship, and moral sensibility in young children.
AB  - Relations between an early interest in violent fantasy and children's social
      understanding, antisocial and emotional behavior, and interactions with friends
      were investigated in 40 "hard-to-manage" preschoolers and 40 control children
      matched for gender, age, and school and ethnic background. Children were filmed
      alone in a room with a friend, and tested on a battery of cognitive tests,
      including false-belief, executive function, and emotion understanding tasks.
      Teachers reported on their friendship quality. At age 6 years, the children's
      understanding of the emotional consequences of antisocial and prosocial actions
      was studied. The hard-to-manage group showed higher rates of violent fantasy;
      across both groups combined, violent fantasy was related to poor executive
      control and language ability, frequent antisocial behavior, displays of anger and
      refusal to help a friend, poor communication and coordination of play, more
      conflict with a friend, and less empathic moral sensibility 2 years later. The
      usefulness of a focus on the content of children's pretend play-in particular,
      violent fantasy-as a window on children's preoccupations is considered.

PMID- 11333081
TI  - Social identity and the development of children's group attitudes.
AB  - This study assessed predictions drawn from social identity theory (SIT; Tajfel &
      Turner) concerning the acquisition of young children's intra- and intergroup
      attitudes and cognitions. In a minimal group study, 5- and 8-year-old children (N
      = 258) were arbitrarily assigned to teams that varied in their drawing ability
      (social status). In addition, the study varied the extent to which the children
      believed they could change teams (social mobility) and whether the team had
      additional positive qualities beyond their drawing skill (social change). The
      children subsequently rated their liking for, and similarity to, the ingroup and
      the outgroup and the extent to which they wished to change groups. Consistent
      with SIT and research with adults, the results indicated that children as young
      as 5 years of age were sensitive to the status of their social group, and that
      ingroup status has important implications for both their desire to remain group
      members as well as their perceived similarity to other group members. The extent
      to which the findings provide support for SIT and the intergroup similarities
      between adults and children are discussed.

PMID- 11333082
TI  - Brazilian adolescents' prosocial moral judgment and behavior: relations to
      sympathy, perspective taking, gender-role orientation, and demographic
      characteristics.
AB  - The goal of this study was to examine demographic and individual difference
      variables that predict level of prosocial moral judgment and self-reported
      prosocial behavior and to test mediating or moderating relations among
      predictors. The relations of prosocial moral reasoning and self-reported
      prosocial behavior to perspective taking, sympathy, age, sociometric status, and
      gender-role orientation were examined with a sample of 149 Brazilian adolescents
      who completed a series of questionnaire measures. Prosocial moral judgment was
      expected to be predicted by both sympathy and perspective taking, whereas
      sympathy or prosocial moral judgment was expected to mediate the relations of
      femininity and perspective taking to prosocial behavior. Self-reported
      perspective taking and sympathy interacted when predicting prosocial moral
      judgment; adolescents who were high in either sympathy or perspective taking (or
      both) scored high in prosocial moral reasoning. A feminine orientation predicted
      sympathy and perspective taking, perspective taking predicted prosocial moral
      reasoning and sympathy, and sympathy had both direct and indirect paths (through
      moral judgment) to prosocial behavior. The findings generally were consistent
      with the contention that both the tendency to take others' perspectives and to
      sympathize are related to level of prosocial moral reasoning, which in turn
      motivates prosocial behavior. Moreover, patterns of correlations among variables
      were similar to those found in the United States.

PMID- 11333083
TI  - Hierarchical structure of moral stages assessed by a sorting task.
AB  - Following criticism of Kohlberg's theory of moral judgment, an empirical re
      examination of hierarchical stage structure was desirable. Utilizing Piaget's
      concept of reflective abstraction as a basis, the hierarchical stage structure
      was investigated using a new method. Study participants (553 Dutch university
      students and 196 Russian high school students) sorted statements in terms of
      moral sophistication. These statements were typical for the different stages of
      moral development as defined in Colby and Kohlberg. The rank ordering performed
      by participants confirmed the hypotheses. First, despite large individual
      variation, the ordering of the statements that gave the best fit revealed that
      each consecutive Kohlbergian stage was perceived to be more morally
      sophisticated. Second, the lower the stage as represented by the items, the
      higher the agreement among the participants in their ranking; and the higher the
      stage as represented by the items, the lower the agreement among the participants
      in the rankings. Moreover, the pivotal point depended on the developmental
      characteristics of the sample, which demonstrated a developmental effect: The
      ordering of statements representative of moral stages below one's own current
      stage was straightforward, whereas the ordering of statements above one's own
      stage was difficult. It was concluded that the Piagetian idea of reflective
      abstraction can be used successfully to operationalize and measure the
      hierarchical nature of moral development.

PMID- 11333084
TI  - Developmental pathways from child maltreatment to peer rejection.
AB  - Using a prospective longitudinal design, rejection by peers, aggressive behavior,
      and social withdrawal were examined among a representative community sample of
      107 maltreated children and an equal number of non-maltreated children. Results
      revealed that chronic maltreatment was associated with heightened risk of
      rejection by peers. Chronically maltreated children were more likely to be
      rejected by peers repeatedly across multiple years from childhood to early
      adolescence. Maltreatment chronicity was also associated with higher levels of
      children's aggressive behavior, as reported by peers, teachers, and children
      themselves. Aggressive behavior accounted in large part for the association
      between chronic maltreatment and rejection by peers. Socially withdrawn behavior
      was associated with peer rejection, but did not account for the association
      between chronic maltreatment and peer rejection. These results held for both
      girls and boys, followed from childhood through early adolescence. Moreover, the
      links among chronic maltreatment, aggressive behavior, and peer rejection were
      already established by early school age. Implications of these results for
      developmental theory and intervention are discussed.

PMID- 11333085
TI  - The relations between parental friendships and children's friendships: self
      report and observational analysis.
AB  - The relations between the quality of mothers' and fathers' friendships and that
      of their children's friendships was examined. One hundred twenty-five fourth
      grade children (9 year olds) completed the Friendship Quality Questionnaire.
      Observational measures of the target children playing with their self-selected
      friend were also collected. Mothers and fathers separately completed the
      Friendship Quality Questionnaire about their best friend. Results indicated that
      children's self-reports and observational measures of friendship quality were not
      highly correlated for girls, but were moderately associated for boys. The quality
      of mothers' and fathers' friendships was related to the quality of children's
      friendships, but the nature of the relations with children's friendships differed
      for girls and boys. The implications of these findings for the socialization of
      friendship patterns and the assessment of children's friendships were noted.

PMID- 11333086
TI  - Antecedents and behavior-problem outcomes of parental monitoring and
      psychological control in early adolescence.
AB  - The early childhood antecedents and behavior-problem correlates of monitoring and
      psychological control were examined in this prospective, longitudinal, multi
      informant study. Parenting data were collected during home visit interviews with
      440 mothers and their 13-year-old children. Behavior problems (anxiety/depression
      and delinquent behavior) were assessed via mother, teacher, and/or adolescent
      reports at ages 8 through 10 years and again at ages 13 through 14. Home
      interview data collected at age 5 years were used to measure antecedent parenting
      (harsh/reactive, positive/proactive), family background (e.g., socioeconomic
      status), and mother-rated child behavior problems. Consistent with expectation,
      monitoring was anteceded by a proactive parenting style and by advantageous
      family-ecological characteristics, and psychological control was anteceded by
      harsh parenting and by mothers' earlier reports of child externalizing problems.
      Consistent with prior research, monitoring was associated with fewer delinquent
      behavior problems. Links between psychological control and adjustment were more
      complex: High levels of psychological control were associated with more
      delinquent problems for girls and for teens who were low in preadolescent
      delinquent problems, and with more anxiety/depression for girls and for teens who
      were high in preadolescent anxiety/depression.

PMID- 11333087
TI  - The "test-tube" generation: parent-child relationships and the psychological well
      being of in vitro fertilization children at adolescence.
AB  - The introduction of in vitro fertilization (IVF) at the end of the 20th century
      constituted a fundamental change in the way in which families could be created,
      and by the start of the new millennium an increasing number of children have been
      (and are being) born as a result of this procedure. This article presents
      findings of a longitudinal study of the first cohort of children conceived by IVF
      to reach adolescence. Thirty-four IVF families, 49 adoptive families, and 38
      families with a naturally conceived child were compared on standardized interview
      and questionnaire measures of parent-child relationships and children's
      psychological well-being. The few differences in parent-child relationships that
      were identified appeared to be associated with the experience of infertility
      rather than with IVF per se. The IVF children were found to be functioning well
      and did not differ from the adoptive or naturally conceived children on any of
      the assessments of social or emotional adjustment.

PMID- 11333088
TI  - Longitudinal study of young children's responses to challenging achievement
      situations.
AB  - Three studies were conducted to replicate and extend Dweck's findings regarding
      young children's responses to challenging achievement situations. Dweck's
      dichotomous helplessness classification system (i.e., task choice, task choice
      reason) was replicated with kindergartners, n = 235 (50% male), and first
      graders, n = 70 (46% male). To test whether individual differences in young
      children's responses to challenging situations are stable over time, 1- and 5
      year follow-ups of the kindergartners were conducted. On the basis of children's
      responses on age-appropriate behavioral tasks, a composite of cognitive,
      behavioral, and affective helplessness indices predicted helplessness at 1 and 5
      years later, n = 114 (50% male), above and beyond kindergarten task ability and
      gender, p<.05. Kindergarten helplessness predicted teacher ratings of children's
      helplessness 5 years later as well, p<.05. The implications of these findings for
      early intervention are discussed.

PMID- 11333089
TI  - Early teacher-child relationships and the trajectory of children's school
      outcomes through eighth grade.
AB  - This study followed a sample of 179 children from kindergarten through eighth
      grade to examine the extent to which kindergarten teachers' perceptions of their
      relationships with students predict a range of school outcomes. Kindergarten
      teachers rated children's behavior and the quality of the teacher-child
      relationship. Follow-up data from first through eighth grade were organized by
      epoch and included academic grades, standardized test scores, work-habit ratings,
      and discipline records. Relational Negativity in kindergarten, marked by conflict
      and dependency, was related to academic and behavioral outcomes through eighth
      grade, particularly for children with high levels of behavior problems in
      kindergarten and for boys generally. These associations remained significant
      after controlling for gender, ethnicity, cognitive ability, and behavior ratings.
      The results have implications for theories of the determinants of school success,
      the role of adult-child relationships in development, and a range of early
      intervention and prevention efforts.

PMID- 11333090
TI  - A mediational model for the impact of exposure to community violence on early
      child behavior problems.
AB  - This study examined how maternal distress mediates the link between exposure to
      community violence (CV) and the development of early child behavior problems.
      Research was conducted among 160 children, 3,0 to 5,11 in age, who resided in
      high-crime neighborhoods. Using structural equation modeling, latent variables
      were constructed to identify model components: maternal socioeconomic status
      (SES) and public assistance status, exposure to CV (maternal perceptions of local
      violence, social disorder, and fear of crime; and frequency of child cowitnessing
      violent events), family aggression (partner aggression toward mother and partner
      aggression toward child), maternal distress (global distress and posttraumatic
      stress disorder symptoms), and early child behavior problems (internalizing and
      externalizing). Bivariate correlations indicated that CV, maternal distress, and
      early child behavior problems were significantly intercorrelated. A series of
      structural equation models was specified to estimate the direct and indirect
      effect of CV on early child behavior problems. A direct model indicated a
      significant path from CV to early child behavior problems, after controlling for
      maternal SES and family aggression. The direct CV-early child behavior problems
      path diminished, however, when maternal distress was included in the model, after
      controlling for maternal SES and family aggression. Results are consistent with a
      mediation model of the impact of maternal distress symptoms on the link between
      CV and early child behavior problems.

PMID- 11333091
TI  - Mathematical modeling to define optimum operating room staffing needs for trauma
      centers.
AB  - BACKGROUND: Level II trauma centers may be verified (1999, American College of
      Surgeons Committee on Trauma) with an on-call operating room team if the
      performance-improvement program shows no adverse outcomes. Using queuing and
      simulation methodology, this study attempted to add a volume guideline. STUDY
      DESIGN: Data from 72 previously verified trauma centers identified multiple
      demographic factors, including specific information about the first trauma
      related operation that was done between 11:00 PM and 7:00 AM each month for 12
      consecutive months. RESULTS: The annual admissions averaged 1,477 for 37 Level I
      trauma centers, 802 for 28 Level II trauma centers, 481 for 4 Level III trauma
      centers, and 731 for 3 pediatric trauma centers. The annual admissions correlated
      with the number of operations done between 11:00 PM and 7:00 AM (p < 0.001).
      These 946 operations were performed by general surgery (39%), neurosurgery (8%),
      orthopaedic surgery (33%), another specialty (9%), or multiple services (10%).
      Admission to operation time was within 30 minutes for 12.1% of patients (2.6% for
      blunt and 24.1% for penetrating injuries). The probability of operation within 30
      minutes of arrival varied with the number of admissions and with the percentage
      of penetrating versus blunt injuries. The likely number of operations from 11:00
      PM to 7:00 AM would be 19 for 500 annual admissions, 26 for 750 annual
      admissions, and 34 for 1,000 annual admissions, with 5.83, 7.98, and 10.13
      patients, respectively, going to operation within 30 min. The probability that
      two rooms would be occupied simultaneously was 0.14 and 0.24 for centers
      admitting 500 and 1,000 patients, respectively. CONCLUSIONS: Trauma centers
      performing fewer than six operations between 11:00 PM and 7:00 AM per year could
      conserve resources by using an immediately available on-call team, with responses
      monitored by the performance-improvement program.

PMID- 11333092
TI  - Incidental pregnancy in trauma patients.
AB  - BACKGROUND: The rate of incidental pregnancy in trauma patients and the incidence
      of associated fetal mortality, to our knowledge, have not been previously
      reported. The early diagnosis of pregnancy in trauma patients has become even
      more difficult because rapid pregnancy screens have been eliminated because of
      quality control issues. We determined the rate of incidental pregnancy and the
      sequelae of delayed diagnosis, including fetal radiation exposure and mortality.
      STUDY DESIGN: Data were analyzed retrospectively on all patients in whom
      pregnancy was diagnosed during a trauma admission during a 4-year period (1995 to
      1999). Pregnancy was confirmed by beta-HCG testing and gestational age estimated
      by an obstetrician by ultrasonography. Pregnancy outcomes were determined by a
      prospective telephone survey. RESULTS: One hundred fourteen (2.9%) of the 3,976
      women (age 15 to 40 years) admitted to the trauma center were found to be
      pregnant. Thirteen (11.0%) were incidental pregnancies, of which 9 (8.0%) were
      newly diagnosed. Mean gestational age was significantly lower in the newly
      diagnosed pregnancies (6.9 versus 20.5 weeks, p < 0.0005). Fetal mortality in
      this group was significantly higher (100% versus 25%, p < 0.0005). The mean
      initial radiation exposure of all patients was 4.5 rads. Cumulative radiation
      exposure exceeded 5 rads in 85% of patients. CONCLUSIONS: Trauma patients
      diagnosed with incidental pregnancy are routinely exposed to doses of radiation
      exceeding the recommendations of the American College of Obstetrics and
      Gynecologists. Reinstitution of the rapid pregnancy test should be considered in
      all female trauma victims of childbearing age. This may promote a reduction in
      fetal radiation exposure and perhaps influence a portion of the fetal mortality
      in those patients with newly diagnosed incidental pregnancy.

PMID- 11333093
TI  - Bedside insertion of inferior vena cava filters in the intensive care unit.
AB  - BACKGROUND: Several authors have showed that bedside insertion of inferior vena
      cava filters (IVCF) is feasible and cost effective, with the additional benefit
      of not having to transport a critically ill patient to the operating room or
      radiology department. The objective of this study was to examine our experience
      of 158 IVCF insertions at the bedside in the intensive care unit. STUDY DESIGN: A
      prospective, observational study of bedside IVCF insertion performed by the
      authors from February 1996 through August 2000 was undertaken. RESULTS: One
      hundred fifty-eight patients underwent bedside IVCF insertion in the intensive
      care unit. The mean age was 42.2 years (SD 17.5 years). The mean Injury Severity
      Score of the trauma patients was 27.3 (SD 14.5). The majority of patients (90%)
      had a prophylactic indication for IVCF insertion using our institutional
      guidelines for venous thromboembolic prophylaxis for trauma patients. All IVCF
      insertions were successfully performed at the bedside after iodinated contrast or
      carbon dioxide cavography. The mortality was 11% (n = 18), none attributable to
      the IVCF insertion or cavagram. There was one asymptomatic cava occlusion and one
      postinsertion pulmonary embolus in a patients with a subclavian vein thrombosis.
      CONCLUSIONS: Our results demonstrate the safety and efficacy of IVCF insertion at
      the bedside in the ICU. This method offers less resource use and more safety for
      critically ill patients, avoiding the hazards of intrahospital transport.

PMID- 11333094
TI  - What is the yield of intraoperative ultrasonography during partial hepatectomy
      for malignant disease?
AB  - BACKGROUND: Previous studies have shown that intraoperative ultrasonography
      (IOUS) during hepatic resection for malignancy changes the operative plan or
      identifies occult unresectable disease in a large proportion of patients. This
      study was undertaken to reassess the yield of IOUS in light of recent
      improvements in preoperative staging. STUDY DESIGN: Patients with potentially
      resectable primary or metastatic hepatic malignancies subjected to exploration,
      bimanual palpation of the liver, and IOUS were evaluated prospectively.
      Intraoperative findings were recorded, and preoperative imaging studies were
      reanalyzed by radiologists blinded to the intraoperative findings. The extent of
      disease based on preoperative imaging was compared with the intraoperative
      findings. RESULTS: From October 1997 until November 1998, 111 patients were
      evaluated. At exploration, a total of 77 new findings or findings different than
      suggested on the imaging studies were identified in 61 patients (55%), the most
      common of which was additional hepatic tumors (n = 37). Thirty-five of 77 (45%)
      new findings were identified by IOUS alone and 10 (13%) by palpation alone; the
      remainder were identified by both palpation and IOUS. Forty-seven of 61 patients
      (77%) underwent a complete resection despite new intraoperative findings, with a
      modification (n = 28) or no change (n = 19) in the planned operation. Twenty-one
      patients (19%) had new findings identified only on IOUS. Thirteen of these
      patients underwent resection with no change in the operative plan, six underwent
      a modified resection and two were considered to have unresectable disease based
      solely on the findings of IOUS. CONCLUSIONS: In patients with hepatic
      malignancies submitted to a potentially curative resection, new intraoperative
      findings or findings different than suggested on preoperative imaging studies are
      common. But resection with no change in the operative plan or a modified
      resection is still possible in the majority of patients despite such findings.
      The findings on IOUS alone rarely lead to a change in the operative plan.

PMID- 11333095
TI  - Anorexia and the effect of internal biliary drainage on food intake in patients
      with obstructive jaundice.
AB  - BACKGROUND: Anorexia is a frequent finding in patients with biliary obstruction
      (BO). This study investigates the role of biochemical and hormonal factors in the
      pathogenesis of reduced food intake in BO and the effects of internal biliary
      drainage. STUDY DESIGN: Sixty-two patients with BO were prospectively
      investigated. Transaminases, amylase, cholecystokinin, secretin, bile acids,
      tumor necrosis factor-alpha, and endotoxin were determined at admission. Caloric
      intake was quantified by a controlled diet. In a subset of 27 patients, studies
      were repeated after internal biliary drainage. RESULTS: Sixty-six percent of
      patients had spontaneous food intakes below the estimated caloric requirements.
      Serum bilirubin, alkaline phosphatase, and cholecystokinin plasma levels were
      independent predictor factors for calorie intake (p = 0.0001). After internal
      biliary drainage, cholestasis parameters and cholecystokinin concentrations
      decreased significantly; this was associated with an improvement of spontaneous
      food intake in both benign and malignant biliary obstruction (p < 0.01 and p <
      0.05, respectively). CONCLUSIONS: Decreased food intake in BO was associated with
      the degree of obstruction and with increased cholecystokinin plasma levels.
      Biliary drainage improved biochemical and food intake derangements.

PMID- 11333096
TI  - Fibrin sealant reduces the duration and amount of fluid drainage after axillary
      dissection: a randomized prospective clinical trial.
AB  - BACKGROUND: Patients who have axillary dissections during lumpectomy or modified
      radical mastectomy for breast carcinoma accumulate serosanguinous fluid,
      potentially resulting in a seroma. Currently accepted practice includes insertion
      of one or more drains for fluid evacuation. This multicenter, randomized,
      controlled, phase II study was undertaken to evaluate whether a virally
      inactivated, investigational fibrin sealant is safe and effective when used as a
      sealing agent to reduce the duration and volume of serosanguinous fluid drainage
      and to determine the dose response of this effect. STUDY DESIGN: Patients
      undergoing lumpectomy or modified radical mastectomy were randomized to treatment
      with 4, 8, or 16 mL of fibrin sealant or control (no agent) at the axillary
      dissections site. Patients undergoing modified radical mastectomy also received
      an additional 4 or 8 mL of fibrin sealant at the skin flap site. Efficacy was
      evaluated by the number of days required for wound drainage and the volume of
      fluid drainage compared with control. Safety was confirmed by clinical course,
      the absence of viral seroconversion, and no major complications attributable to
      the sealant. RESULTS: The 4-mL axillary dissection dose of fibrin sealant
      significantly reduced the duration and quantity of fluid drainage from the axilla
      following lumpectomy (p < or = 0.05). In the modified radical mastectomy
      patients, a 16-mL axillary dissection dose combined with an 8-mL skin flap dose
      was significantly effective in reducing the number of days to drain removal (p <
      or = 0.05) and fluid drainage (p < or = 0.01). There were no fibrin sealant
      patient viral seroconversions and no major complications attributable to the
      sealant. A number of wound infections were noted, although this may represent a
      center-specific effect. CONCLUSIONS: Application of fibrin sealant following
      axillary dissection at the time of lumpectomy or modified radical mastectomy can
      significantly decrease the duration and quantity of serosanguinous drainage. The
      viral safety of the product was also supported.

PMID- 11333097
TI  - Surgical treatment of patients with T2 gallbladder carcinoma invading the
      subserosal layer.
AB  - BACKGROUND: Because T2 carcinoma of the gallbladder that invades perimuscular
      connective tissue without extension beyond serosa or into the liver has a hope
      for longterm survival, we attempted to clarify significant prognostic factors
      with respect to tumor- and surgery-related variables. STUDY DESIGN: Of 65
      patients with gallbladder carcinoma who had undergone surgical resection from
      1983 to 1999, 28 had T2 carcinoma histologically proved. The significance of
      variables for survival was examined by the Kaplan-Meier method and log-rank test
      followed by multivariate analyses using Cox's proportional hazard model. RESULTS:
      There were 17 patients with stage II carcinoma (T2 N0 M0), 6 with stage III (T2
      N1 M0), and 5 with stage IVB. Lymph node metastasis was present in 11 patients
      (39%) and it reached to the peripancreatic head region (N2) in 5 of them.
      Lymphatic, venous, and perineural invasions were found in 68%, 57%, and 43%,
      respectively. With respect to tumor factors, the absence of perineural invasion
      (Odds ratio [OR] 16.77, 95% confidence interval [CI] 2.17-129.94, p = 0.0069),
      absence of lymph node metastasis (OR 15.00, 95% CI 2.08-108.33, p = 0.0073), and
      stage II (II versus III and IVB, OR 15.00, 95% CI 2.08-108.33, p = 0.0073) were
      significant factors related to good postoperative survival in the multivariate
      analysis. Surgical procedure (radical resection versus cholecystectomy, OR 4.31,
      95% CI 1.34-13.82, p = 0.0142) and surgical margin (OR 7.41, 95% CI 2.19-25.13, p
      = 0.0013) were significant factors in the univariate analysis. Cancer-free
      surgical margins provided a significantly better survival (5-year survival rate,
      62%); none with cancer-positive surgical margins survived for more than 27
      months. In the multivariate analysis, surgical procedure was significant (OR
      25.49, 95% CI 1.62-400.72, p = 0.021). Radical surgery, including extended
      cholecystectomy (resection of the gallbladder together with the gallbladder bed
      of the liver) and anatomic resection of liver segment 5 and of the lower part of
      segment 4, gave a significantly better 5-year survival rate than cholecystectomy
      (59% versus 17%). The 5-year survival rate after radical resection in patients
      with stage II was 75%; that in patients with stage III and IVB was 33%.
      CONCLUSIONS: Results suggest that radical surgery is the treatment of choice for
      patients with T2 carcinoma of the gallbladder. The presence of lymph node
      metastasis, perineural invasion, or both suggests the necessity of additional
      treatment after radical surgery.

PMID- 11333098
TI  - Asymptomatic carotid stenosis and unrelated operations: should we be more
      aggressive?
AB  - BACKGROUND: Carotid lesions will often remain asymptomatic during the
      perioperative period, so prophylactic carotid endarterectomy (CEA) has not been
      advocated before other operations. The purpose of this study was to characterize
      the clinical manifestations of new neurologic symptoms occurring in patients with
      previously asymptomatic carotid occlusive disease who have undergone recent
      operations. STUDY DESIGN: We performed a retrospective review of patients
      developing neurologic symptoms attributable to carotid occlusive disease after
      unrelated operations. RESULTS: Eleven patients (mean age 68+/-6.4 years, 8 men, 3
      women) developed new neurologic symptoms from previously asymptomatic
      extracranial carotid stenoses after 11 unrelated procedures. Neurologic events
      included hemispheric stroke (n = 10) and amaurosis fugax (n = 1). Two
      intraoperative strokes occurred (one mastectomy, one prostatectomy). Other events
      occurred a mean of 5.8+/-5 (range 1 to 16) days after aortic surgery (n = 2),
      infrainguinal bypass (n = 3), contralateral CEA for symptomatic disease (n = 2),
      incisional herniorrhaphy (n = 1), and prostate surgery (n = 1). Responsible
      internal carotid artery lesions were all stenoses greater than 80%; seven were
      clearly greater than 90%. Those suffering intraoperative stroke or stroke within
      24 hours of operation (n = 3) were not receiving antithrombotic therapy. All
      other events (n = 8) occurred despite the use ofantiplatelet or anticoagulant
      agents. Four underwent emergent CEA. Four had elective CEA performed after
      reaching a neurological recovery plateau. CONCLUSIONS: Critical, asymptomatic
      internal carotid artery stenoses may cause neurologic symptoms after unrelated
      surgical procedures.

PMID- 11333099
TI  - What's new in neurological surgery.

PMID- 11333100
TI  - What's new in surgical oncology.

PMID- 11333101
TI  - Future directions in antithrombotic therapy: emphasis on venous thromboembolism.

PMID- 11333102
TI  - Gastric MALT lymphoma in a Helicobacter pylori-negative patient: a case report
      and review of the literature.

PMID- 11333103
TI  - Meckel's diverticulum.

PMID- 11333104
TI  - Total gastrectomy with jejunal substitute "stomach".

PMID- 11333105
TI  - Horseshoe ischiorectal abscess originating from dorsal intersphincteric
      cryptoglandular abscess.

PMID- 11333106
TI  - Minimally invasive, nonendoscopic thyroid surgery.

PMID- 11333107
TI  - Ethical principles for everyone in health care.

PMID- 11333108
TI  - Ethical principles for everyone in health care.

PMID- 11333109
TI  - Ethical principles for everyone in health care.

PMID- 11333110
TI  - Proton transfer and ferredoxin I: the secrets of redox-driven proton transfer
      between solvent and a buried iron-sulphur cluster.

PMID- 11333111
TI  - Garbage catastrophe theory of aging: imperfect removal of oxidative damage?
AB  - Increasing evidence suggests an important role of oxidant-induced damage in the
      progress of senescent changes, providing support for the free radical theory of
      aging proposed by Harman in 1956. However, considering that biological organisms
      continuously renew their structures, it is not clear why oxidative damage should
      accumulate with age. No strong evidence has been provided in favor of the concept
      of aging as an accumulation of synthetic errors (e.g. Orgel's 'error-catastrophe'
      theory and the somatic mutation theory). Rather, we believe that the process of
      aging may derive from imperfect clearance of oxidatively damaged, relatively
      indigestible material, the accumulation of which further hinders cellular
      catabolic and anabolic functions. From this perspective, it might be predicted
      that: (i) suppression of oxidative damage would enhance longevity; (ii)
      accumulation of incompletely digested material (e.g. lipofuscin pigment) would
      interfere with cellular functions and increase probability of death; (iii)
      rejuvenation during reproduction is mainly provided by dilution of undigested
      material associated with intensive growth of the developing organism; and (iv)
      age-related damage starts to accumulate substantially when development is
      complete, and mainly affects postmitotic, cells and extracellular matrix, not
      proliferating cells. There is abundant support for all these predictions.

PMID- 11333112
TI  - Evaluation of the process for superoxide production by NADPH oxidase in human
      neutrophils: evidence for cytoplasmic origin of superoxide.
AB  - We present an up-to-date insight into the function of NADPH oxidase in human
      neutrophils, the signalling pathways involved in activation of this enzyme and
      the process of association of its components with the cytoskeleton. We also
      discuss the functional implications of morphological studies revealing
      localization of the sites of NADPH oxidase activity. An original model of the
      process of superoxide (O2*-) production in human neutrophils is shown.
      Organization of NADPH oxidase is associated with several components. Upon
      stimulation, tri-phox cytosolic components of NADPH oxidase (p40-phox, p47-phox
      and p67-phox) bind to actin filaments. This process involves other actin-binding
      proteins, such as cofilin and coronin. Activated protein kinase C, translocated
      from the plasma membrane, phosphorylates cytosolic components at a scaffold of
      cytoskeleton. Subsequently, p40-phox, responsible for maintaining the resting
      state of NADPH oxidase, is separated from other two cytosolic phox proteins
      following an attachment of the active form of small GTP-binding protein Rac to
      p67-phox. Cytosolic duo-phox proteins (p47-phox and p67-phox) conjugate with
      membrane components (gp91-phox, p22-phox and Rapla) of NADPH oxidase residing
      within membranes of intracellular compartments. This chain of events triggers
      production of O2*-. Then, oxidant-producing intracellular compartments associate
      with the plasma membrane. Eventually, intracellularly produced O2*- is released
      to the extracellular environment through the orifice formed by fusion of oxidant
      producing compartments with the plasma membrane. Intracellular movement of the
      oxidant-producing compartments may be regulated by myosin light chain kinase. The
      review emphasizes that functional assembly of NADPH oxidase and, therefore,
      generation of O2*- is accomplished essentially within the intracellular
      compartments. Upon neutrophil stimulation, intracellularly generated O2*- is
      transported to the plasma membrane to be released and to ensure host defense
      against infection.

PMID- 11333113
TI  - How much is needed for the C-E bounce?

PMID- 11333114
TI  - Catalase-deficient tobacco plants: tools for in planta studies on the role of
      hydrogen peroxide.
AB  - Adequate responses to environmental changes are crucial for plant growth and
      survival. However, the molecular and biochemical mechanisms involved are poorly
      understood and the signaling networks remain elusive. The accumulation of active
      oxygen species (AOS) is a central theme during plant responses to both biotic and
      abiotic stresses. In both situations, AOS can play two divergent roles: either
      exacerbating damage or activating multiple defense responses, thereby acting as
      signal molecules. Such a dual function was first described in pathogenesis, but
      also recently has been demonstrated during several abiotic stress responses. To
      allow for these different roles, cellular levels of AOS must be tightly
      controlled. This control can be attained through a diverse battery of oxidant
      scavengers. Perturbation of this scavenging capacity can lead to dramatic
      imbalances of AOS concentrations, leading to a modified redox status. Here, we
      summarize mainly the work done on plants that are deficient in catalase activity.
      These plants not only revealed the importance of catalase in coping with
      environmental stress but also provided us with a powerful tool to investigate the
      (multiple) roles of H2O2 in an intact plant system.

PMID- 11333115
TI  - Photochemiluminescent detection of antiradical activity. V. Application in
      combination with the hydrogen peroxide-initiated chemiluminescence of blood
      plasma proteins to evaluate antioxidant homeostasis in humans.
AB  - Disturbance of the steady state between pro- and antioxidants in tissues is an
      important aetiopathogenetic factor. Two method--(i) photosensitized
      chemiluminescence for detection of antiradical activity and (ii) hydrogen
      peroxide-initiated chemiluminescence of plasma proteins (CLP) and erythrocytes
      (CLE)--were tested in 136 healthy donors and 82 patients with untreated breast
      tumours for their applicability to detecting disturbances in antioxidant
      homeostasis in humans. The total antiradical capacity of water-soluble substances
      (ACW) and its urate-independent proportion (ACU) were lower (P <0.05) and CLP
      higher (P <0.001) in smokers in comparison to non-smokers. A significant negative
      correlation was found between the content of ascorbate in plasma and the
      intensity of CLP: r = -0.39, P <0.001. A significant reduction in ACU and
      increased values of CLP and CLE were seen according to the stage of disease in
      breast cancer patients. On the basis of these observations and model experiments
      we suggest that hydrogen peroxide-initiated chemiluminescence can serve as a
      parameter of oxidative modification of blood components and, in combination with
      the antioxidant parameters, can be used to describe the antioxidant homeostasis
      in humans and possibly to have value as a predictor of disease states.

PMID- 11333116
TI  - Fatty acid chlorohydrins and bromohydrins are cytotoxic to human endothelial
      cells.
AB  - Reaction of unsaturated lipids with the hypohalous acids (hypochlorous acid and
      hypobromous acid) results in the addition of the halide (X) across double bonds
      to form halohydrins (-CH2CH(OH)CH(X)CH2-). These modified lipids could be
      potentially destabilising to cell membranes due to their increased polarity. We
      have investigated the effect of pre-formed halohydrins on human umbilical vein
      endothelial cells (HUVEC) by incubating cultured cells with oleic acid micelles
      containing chlorohydrins or bromohydrins. Cell detachment and necrotic death were
      observed with increasing doses of halohydrins, whereas the cells were unaffected
      by equivalent doses of oleic acid. Bromohydrins caused more lysis than did
      chlorohydrins at equivalent doses. Complete lysis was seen with 200 microM fatty
      acid/chlorohydrin micelles and with 50 microM fatty acid/bromohydrin micelles.
      Chlorohydrin uptake was much less than the oleic acid control whereas
      bromohydrins were incorporated into the endothelial cells similarly to oleic
      acid. This difference or the bulkier nature of the bromohydrins could account for
      their increased toxicity. This study has demonstrated the potential toxicity of
      the halohydrins, and implications for their formation in inflammation are
      discussed.

PMID- 11333117
TI  - The new US Dietary Reference Intakes for vitamins C and E.

PMID- 11333118
TI  - Novel cellular defenses against iron and oxidation: ferritin and autophagocytosis
      preserve lysosomal stability in airway epithelium.
AB  - Adsorbed to a variety of particles, iron may be carried to the lungs by
      inhalation thereby contributing to a number of inflammatory lung disorders. Redox
      active iron is a potent catalyst of oxidative processes, but intracellularly it
      is bound primarily to ferritin in a non-reactive form and probably is
      catalytically active largely within the lysosomal compartment. Damage to the
      membranes of these organelles causes the release to the cytosol of a host of
      powerful hydrolytic enzymes, inducing apoptotic or necrotic cell death. The
      results of this study, using cultured BEAS-2B cells, which are adenovirus
      transformed human bronchial epithelial cells, and A549 cells, which have
      characteristics similar to type II alveolar epithelial cells, suggest that the
      varying abilities of different types of lung cells to resist oxidative stress may
      be due to differences in intralysosomal iron chelation. Cellular ferritin and
      iron were assayed by ELISA and atomic absorption, while plasma and lysosomal
      membrane stability were evaluated by the acridine orange uptake and trypan blue
      dye exclusion tests, respectively. Normally, and also after exposure to an iron
      complex, A549 cells contained significantly more ferritin (2.26 +/- 0.60 versus
      0.63 +/- 0.33 ng/microg protein, P <0.001) and less iron (0.96 +/- 0.14 versus
      1.48 +/- 0.21 ng/microg protein, P <0.05) than did BEAS-2B cells. Probably as a
      consequence, iron-exposed A549 cells displayed more stable lysosomes (P <0.05)
      and better survival (P <0.05) following oxidative stress. Following starvation
      induced autophagocytosis, which also enhances resistance to oxidant stress, the
      A549 cells showed a significant reduction in ferritin, and the BEAS-2B cells did
      not. These results suggest that intralysosomal ferritin enhances lysosomal
      stability by iron-chelation, preventing Fenton-type chemistry. This notion was
      further supported by the finding that endocytosis of apoferritin, added to the
      medium, stabilized lysosomes (P <0.001 versus P <0.01) and increased survival (P
      <0.01 versus P <0.05) of iron-loaded A549 and BEAS-2B cells. Assuming that
      primary cell lines of the alveolar and bronchial epithelium behave in a similar
      manner as these respiratory cell lines, intrabronchial instillation of
      apoferritin-containing liposomes may in the future be a treatment for iron
      dependent airway inflammatory processes.

PMID- 11333119
TI  - Detection of invasion-related chromosomal changes in highly and weakly invasive
      melanoma cell clones by a modified comparative genomic hybridization approach.
AB  - Invasion is a key step in the systemic spread of tumour cells. The aim of this
      study was to investigate whether specific chromosomal aberrations in melanoma
      occur during acquisition of a strongly invasive phenotype. We previously selected
      highly and weakly invasive cell clones from the human melanoma cell line Mel Im.
      Both cell clones retained a stable phenotype over more than 40 passages,
      revealing a five-fold difference in their invasive potential in vitro. Direct
      comparative genomic hybridization (CGH) (modified CGH) of the two cell clones was
      used as a powerful tool to screen for different chromosomal aberrations in both
      clones. Standard CGH and fluorescence in situ hybridization (FISH) was performed
      to verify the results of this improved technique. In general, the CGH pattern
      showed a high degree of identity consistent with the fact that the cell lines
      represent subclones of the same cell line. However, a few defined changes between
      the two cell clones were observed, including loss of 1q21-qter, 4q, 11p14-pter,
      19q and 20p in the highly invasive cell clone. Two of the regions (1q and 11p)
      have already been suggested to be involved in melanoma progression, whereas
      changes in the others have not been detected before. In summary, our direct CGH
      approach proved to be suitable for fast and direct comparison of two cell types
      and allowed the identification of two known and three novel chromosomal changes
      involved in the acquisition of a strongly invasive melanoma cell phenotype.

PMID- 11333120
TI  - Association between germ cell tumours, large numbers of naevi, atypical naevi and
      melanoma.
AB  - Identifying groups of subjects at high risk for the development of melanoma is
      crucial for the early diagnosis of curable tumours. In the present study, we
      performed a skin examination in a group of 63 patients followed up after
      treatment of germ cell tumours (GCTs) who were referred to the dermatologist for
      multiple pigmented cutaneous spots. Forty-nine patients bearing a great number of
      naevi or atypical naevi were included in the study. Two thin cutaneous melanomas
      were discovered in two patients. In addition, a third patient had had a
      conjunctival melanoma since treatment of the GCT. Our study confirms the presence
      of atypical naevi in a subgroup of GCT patients, who are shown to be at high risk
      of developing melanoma. Patients harbouring multiple pigmented spots should be
      referred for a skin examination aimed at early detection of curable melanomas,
      and should be advised to protect themselves from sun exposure.

PMID- 11333121
TI  - The body site distribution of melanocytic naevi in 6-7 year old European
      children.
AB  - The number and size of melanocytic naevi are the main predictors of cutaneous
      melanoma. Naevus development per unit of skin surface is greatest during
      childhood. We assessed the body distribution of naevi 2-4.9 mm and > or = 5 mm in
      649 European children aged 6-7 years old from Brussels (Belgium), Bochum
      (Germany), Lyon (France) and Rome (Italy). The numbers of naevi 2-4.9 mm and
      naevi > or = 5 mm were strongly correlated, especially on the trunk. For naevi 2
      4.9 mm, the highest relative densities were found on the face, back, shoulders
      and the external surface of the arms. The lowest relative densities were found on
      the hands, legs, feet and abdomen. The relative density of naevi > or = 5 mm was
      higher on the trunk than on any other body site. Similar body distributions were
      observed in both sexes and at each centre. The body site distribution of naevi 2
      4.9 mm seemed to parallel the usual sun exposure patterns of young European
      children. It is suggested that the development of naevi > or = 5 mm might be a
      marker of the vulnerability of melanocytes to the harmful effects of solar
      radiation. Vulnerability would be maximal on the back, and would decrease from
      proximal to distal skin areas, with melanocytes of the hands and feet having the
      lowest vulnerability. The number of naevi acquired on a specific area of skin
      would result from the combined effects of local vulnerability to solar radiation
      and local sun exposure history. The origin of acquired body site differences in
      the susceptibility of melanocytes to ultraviolet radiation is unknown, although
      it seems to parallel the body site density of sensory innervation.

PMID- 11333122
TI  - A population-based study of familial cutaneous melanoma.
AB  - We studied familial risks in cutaneous melanoma by comparing the occurrence of
      melanoma, or discordant cancer, in two generations, based on the Swedish Family
      Cancer Database of 9.6 million individuals. Offspring were from 0 to 61 years of
      age. Cancers were obtained from the Swedish Cancer Registry for the years 1958 to
      1996. The study was based on 30,170 cases of melanoma. Among these, 196 offspring
      came from families where a parent also presented with melanoma. The overall
      familial hazard ratio (FHR) was 2.47 when a parent had melanoma; an early age of
      onset increased the risk. Multiple primary melanomas in parents increased the FHR
      in offspring, being 2.23 for one, 9.10 for two and up to 83 for more than two
      melanomas in the parent. The number of affected offspring increased the risk of
      melanoma in the parents, from 3.05 when one was affected to 5.12 and 151 when two
      or three offspring were affected, respectively. Melanoma risk to a sibling with
      an affected proband was 3.56. Melanoma in one generation was associated with an
      increased occurrence of squamous cell carcinoma of the skin in the other
      generation. Other weaker associations were found to pancreatic, breast,
      testicular and nervous system cancers and non-Hodgkin lymphomas.

PMID- 11333123
TI  - Under-registration of melanoma in Wales in 1998: use of the capture-recapture
      method to estimate the 'true' incidence.
AB  - Several studies have suggested that melanomas may be significantly under-recorded
      in cancer registries and that smaller, thinner, better prognosis lesions are the
      ones most likely to be missed. A systematic search of three independent sources
      of melanoma data in Wales for 1998 revealed a total of 406 histologically
      confirmed cases, of which only 194 were known to the cancer registry. Eighty-one
      per cent of the total cases were registered on a specialist melanoma register,
      compared with 48% on the cancer registry database. From the cancer registry data
      alone, the world age-standardized incidence rates (WASRs) were 4.3 and 5.8 per
      100,000 for males and females, respectively, but these increased to 8.2 and 10.2
      with the addition of histologically confirmed cases discovered from other
      sources. The capture-recapture method estimated the number of melanomas not
      ascertained by either means to be 140, resulting in a 'true' incidence of 546
      cases for 1998 compared with just 194 cases from the cancer registry data alone.
      The 'true' WASRs are 11.2 and 13.4 per 100,000 for males and females,
      respectively, which are some of the highest in Europe. There was evidence to
      support the hypothesis that smaller, thinner melanomas are more likely to be
      recorded on a specialist melanoma register than on the cancer registry database.

PMID- 11333124
TI  - Non-invasive analysis of melanoma thickness by means of dermoscopy: a
      retrospective study.
AB  - Epiluminescence microscopy (ELM), or dermatoscopy, is a non-invasive technique
      for the diagnosis of cutaneous melanoma that may play a role in the non-invasive,
      preoperative assessment of melanoma thickness. This study investigated the
      correlation between the frequency of appearance of some standard ELM criteria and
      the histological thickness of melanomas. In addition, the possible role of the
      total dermoscopic score (TDS) according to ABCD rule of dermoscopy as a predictor
      of melanoma thickness was analysed. The dermoscopic images of 84 cutaneous
      melanomas were retrospectively investigated to evaluate the presence of 10
      standard ELM criteria, and for each lesion the TDS was established (with
      observers blinded as to the tumour thickness). A statistically significant
      association was found between the presence of an irregular pigment network and
      melanomas with a Breslow index equal to or lower than 0.75 mm (positive
      predictive value of 68%); in contrast, radial streaming, atypical vascular
      pattern and grey-blue areas were associated with melanomas > 0.75 mm (positive
      predictive values of 77%, 65% and 70%, respectively). Of the melanomas thinner
      than 0.76 mm, 82% showed a TDS lower than 6.80 (optimized cut-off point), while
      79% of melanomas thicker than 0.75 mm had a TDS higher than 6.80 (chi2 = 30.815,
      P < 0.001); the positive predictive value of a TDS > 6.80 in the detection of
      lesions thicker than 0.75 mm was 79%. In conclusion, a statistically significant
      correlation does exist between some dermoscopic features and melanoma thickness.
      Both the mostly used dermoscopic methods (standard ELM pattern analysis and the
      ABCD rule of dermatoscopy) may provide useful information in the non-invasive
      assessment of melanoma thickness. However, their diagnostic performance is far
      from 100%; further studies are needed to investigate whether the combination of
      dermoscopy with other non-invasive approaches (e.g. sonometry) may result in an
      overall improvement in the diagnostic performance.

PMID- 11333125
TI  - The dermatoscope: a potential source of nosocomial infection?
AB  - Dermatoscopes are directly placed on the skin of patients and therefore may
      harbour potentially pathogenic bacteria. In this study we assessed bacterial
      contamination of dermatoscopes during routine use and examined the effectiveness
      of isopropyl alcohol and disposable lens covers. Aerobic bacterial cultures were
      performed on randomly selected dermatoscopes after examination of 39 patients. In
      addition, bacterial contamination of dermatoscopes after cleaning with 70%
      isopropyl alcohol and after using a disposable transparent lens cover was tested.
      Bacteria such as Staphylococcus epidermidis, Micrococcus species and
      Corynebacterium species, which are usually present on the skin, were repeatedly
      identified. In addition, rare bacteria such as Moraxella species were found.
      Known nosocomial micro-organisms such as Staphylococcus aureus were recovered
      from hospitalized patients. Disinfection with 70% isopropyl alcohol and the use
      of a disposable lens cover significantly reduced the number of bacteria. Image
      quality was identical with and without the use of a transparent lens cover.
      Dermatoscopes harbour potential pathogens and may be a source of bacterial
      transmission. Isopropyl alcohol is an effective cleaning agent for dermatoscopes.
      Disposable lens covers completely prevented bacterial transmission and are
      therefore recommended for routine dermatoscopy, especially in hospitalized
      patients.

PMID- 11333126
TI  - High collagenase-1 expression correlates with a favourable chemoimmunotherapy
      response in human metastatic melanoma.
AB  - Matrix metalloproteinases (MMPs) are proteolytic enzymes that can degrade
      extracellular matrix and thus enhance metastasis. We have studied the expression
      of two collagenolytic MMPs in 37 samples obtained from 26 patients treated for
      metastatic melanoma. Interestingly, the samples showed a different expression
      pattern of collagenase-1 (MMP-1) and collagenase-3 (MMP-13). The samples with
      high expression levels of MMP-1 (n = 18) were more frequently MMP-13 negative (14
      out of 18), whereas those with low expression levels of MMP-1 (n = 15) were
      predominantly positive for MMP-13 (nine out of 15) (P = 0.027). High expression
      levels of MMP-1 were associated with a favourable response to chemoimmunotherapy.
      Responders (n = 13) frequently had intensively MMP-1-expressing metastases (nine
      out of 13), especially those who achieved a complete response (five out of six).
      Response failures (n = 7) mainly had metastases with a low intensity of MMP-1
      expression (six out of seven) (P = 0.019). There was a tendency towards longer
      survival among patients with intensively MMP-1-expressing tumours (median 14.3
      versus 6.7 months, P = 0.068). The high expression levels of MMP-1 correlated
      with low MIB-1 (to nuclear antigen Ki-67) (P = 0.019) and positivity for MMP-13
      was associated with high MIB-1 expression (P = 0.00048), suggesting that their
      different expression patterns may affect tumour growth and contribute to
      differences in patient survival.

PMID- 11333127
TI  - Metastatic lesions in the joint associated with acute inflammatory arthritis
      after dendritic cell immunotherapy for metastatic melanoma.
AB  - A 47 year old man undergoing immunotherapy for metastatic melanoma with
      autologous dendritic cells pulsed with autologous tumour peptide and hepatitis B
      surface antigen developed acute left ankle arthritis. Gout and acute infection
      were excluded, and an autoimmune aetiology or occult metastasis were considered.
      The arthritis initially subsided with indomethacin, but the symptoms recurred 2
      months later, and magnetic resonance imaging demonstrated metastatic melanoma of
      the left talus. Immunohistochemical staining of a cerebral metastatic deposit
      biopsied 1 week after the onset of arthritis demonstrated T-cell and macrophage
      infiltration of the tumour. In addition, the patient developed melanoma-specific
      delayed type hypersensitivity and cytotoxic T-cell responses after vaccination.
      Thus, the monoarthritis represented an 'appropriate' inflammatory response
      directed against metastatic melanoma.

PMID- 11333128
TI  - Preclinical targeted alpha therapy for subcutaneous melanoma.
AB  - An alpha-emitting immunoconjugate (AIC) against malignant melanoma was prepared
      from the radioisotope bismuth-213 and a melanoma monoclonal antibody, and was
      used to control the growth of subcutaneous melanoma in a nude mouse model.
      Activity tolerances were found to be 8 mCi/kg for intraperitoneal injection of
      the conjugate, and 10 mCi/kg for intralesional injections. Local targeted alpha
      therapy (TAT) via intralesional injections of activities in the range 12.5-200
      microCi shows a very high level of inhibition of tumorigenesis and regression of
      tumours. Results show that isolated cancer cells and preangiogenic cell clusters
      can be eliminated by local TAT, and that intralesional injections of 100 microCi
      of AIC are sufficient to cause complete regression of melanomas with volumes up
      to 300 mm3 without any observed side effects. Systemic TAT was less effective,
      with all tumours experiencing growth delay and limited inhibition of tumour
      growth. These data provide the basis for clinical trials of TAT in recurrent
      subcutaneous melanoma.

PMID- 11333129
TI  - Phase II evaluation of bryostatin-1 in metastatic melanoma.
AB  - In this phase II study we assessed the efficacy of bryostatin-1 (NSC 339555) in
      metastatic melanoma patients when given intravenously either once a week at a
      dose of 25 microg/m2 per day over 24 h for 3 weeks or at 40 microg/m2 per day
      over 72 h every 2 weeks. Treatment courses were repeated every 4 weeks. Patients
      who had received one prior chemotherapy regimen for advanced melanoma, with or
      without biotherapy, were randomized to one or the other bryostatin-1 dose
      schedules until 12 patients were registered to each arm. Because there was one
      confirmed response among the 12 patients who received the 72 h dose schedule, 25
      more patients were added to that arm. No prophylactic medications were given.
      Objective tumour measurements were used to assess the efficacy of the regimen.
      The National Cancer Institutes common toxicity criteria were used to grade
      reactions. In total, 49 patients with metastatic melanoma, none having
      symptomatic brain metastasis, were studied. Of these, 12 patients received the 24
      h bryostatin-1 regimen, while the remaining 37 received the 72 h regimen. One
      patient receiving the 72 h regimen had a partial response lasting over 7 months.
      Muscle pain occurred in over 90% of the patients and was the dose-limiting side
      effect of the 72 h regimen. Grade 3/4 nausea and vomiting were more common on the
      24 h regimen than on the 72 h one (35% versus 5% of patients). There was no
      therapy-related thrombocytopenia. Neutropenia was mild and mainly limited to
      patients receiving the 72 h regimen. Bryostatin-1 has limited activity against
      melanoma when given by 72 h intravenous infusion.

PMID- 11333130
TI  - Phase II randomized study of dacarbazine, carmustine, cisplatin and tamoxifen
      versus dacarbazine alone in advanced melanoma patients.
AB  - This randomized phase II trial was performed to define the activity and toxicity
      of the combination of dacarbazine (DTIC), carmustine (BCNU), cisplatin (DDP) and
      tamoxifen (DBDT regimen) versus DTIC alone in patients with metastatic melanoma.
      Sixty patients with metastatic melanoma were randomly assigned to receive BCNU
      150 mg/m2 intravenously (i.v.) on day 1, cisplatin 25 mg/m2 i.v. daily on days 1
      to 3, DTIC 220 mg/m2 i.v. daily on days 1 to 3 and tamoxifen 160 mg orally daily
      for 7 days prior to chemotherapy (DBDT arm; arm A). Treatment cycles were
      repeated every 28 days, while BCNU was given every two cycles. The DTIC arm (arm
      B) patients received DTIC alone 1200 mg/m2 i.v. on day 1, repeated every 21 days.
      Patients were evaluated every two cycles; responding patients continued the
      treatment for a maximum of 12 cycles. The overall response rate was 26% in the
      DBDT arm and 5% in the DTIC arm. Complete responses were 2.5% for DBDT and 0% for
      DTIC. The median progression-free survival and the median survival were 4 and 9
      months, respectively for DBDT, and 2 and 7 months for DTIC. DBDT was associated
      with significant haematological toxicity: 33% of the patients experienced a grade
      III or IV neutropenia and 28% a grade III or IV thrombocytopenia. In conclusion,
      the overall response rate obtained with DBDT was greater than that obtained with
      DTIC alone; however, this combination increases toxicity with limited impact on
      overall survival.

PMID- 11333131
TI  - Direct antiproliferative effects of melatonin on two metastatic cell sublines of
      mouse melanoma (B16BL6 and PG19).
AB  - The effects of melatonin on the growth of two highly tumorigenic rodent melanoma
      cells were studied in vitro. PG19, an amelanotic mouse melanoma cell line, and
      B16BL6, a melanotic melanoma cell line selected for its invasive potential in
      vitro, were cultured in the presence of different concentrations of melatonin (10
      microM to 0.1 pM). Five days later, viable cells were determined in a
      haemocytometer by the trypan blue exclusion test. Melatonin at concentrations of
      1 nM and 10 pM (within the range of concentrations that correspond to
      physiological night-time and daytime levels in human blood) significantly
      inhibited proliferation in both melanoma cell lines. Subphysiological (0.1 pM) or
      supraphysiological (10 microM to 100 nM) concentrations of melatonin lacked this
      effect. These results support the hypothesis that, at physiological
      concentrations, melatonin exerts a direct inhibitory effect on PG19 and B16BL6
      cells proliferation.

PMID- 11333132
TI  - Hepatocyte growth factor and melanoma: gene transfer studies in human
      melanocytes.
AB  - Hepatocyte growth factor (HGF), a fibroblast-derived protein that affects the
      growth, motility and differentiation of epithelial cells, is a mitogen for human
      melanocytes and has recently been implicated as an important factor for the
      development and dissemination of melanomas. To better define the possible role of
      HGF in the multi-step progression from melanocyte to melanoma cell, we used
      retrovirus-mediated gene transfer to introduce the gene encoding human HGF into
      normal human melanocytes, thus causing these cells to produce a growth factor
      they do not normally express and creating a new autocrine loop as sometimes
      occurs in melanoma cells. Cells were transduced with an efficiency of 6%, and the
      modified cells synthesized and secreted significant levels of HGF (6.6 ng/10(7)
      cells per 24 h) in vitro. Cells expressing HGF had a higher rate of proliferation
      when compared with unmodified cells and formed large, dense, melanin-positive
      colonies on a plastic surface. Immunostaining showed HGF-positive melanocytes
      with varying levels of expression, and HGF protein was detected throughout the
      whole cell. Although proliferation of HGF-expressing melanocytes was enhanced,
      they failed to form colonies in a soft agar assay. These results suggest that
      expression of HGF, by virtue of its ability to enhance proliferation and cell
      clustering, may play a role in the multi-step process of transformation, but an
      autocrine signal of HGF alone is not sufficient for malignant transformation.

PMID- 11333133
TI  - Betulinic acid reduces ultraviolet-C-induced DNA breakage in congenital
      melanocytic naeval cells: evidence for a potential role as a chemopreventive
      agent.
AB  - Melanoma transformation progresses in a multistep fashion from precursor lesions
      such as congenital naevi. Exposure to ultraviolet (UV) light promotes this
      process. Betulinic acid (BA) was identified by our group as a selective inhibitor
      of melanoma that functions by inducing apoptosis. The present study was designed
      to investigate the effect of BA and UV-C (254 nm) on cultured congenital
      melanocytic naevi (CMN) cells, using the single-cell gel electrophoresis (comet)
      assay to detect DNA damage. Exposure to UV light induced a 1.7-fold increase in
      CMN cells (P = 0.008) when compared with controls. When a p53 genetic suppressor
      element that encodes a dominant negative polypeptide (termed GSE56) was
      introduced into the CMN cells, the transfected cells were more sensitive to UV
      induced DNA breakage. This suggests that p53 can protect against UV-induced DNA
      damage and subsequent melanoma transformation. Pretreatment with BA (3 microm)
      for 48 h resulted in a 25.5% reduction in UV-induced DNA breakage in the CMN
      cells (P = 0.023), but no changes were observed in the transfected cells.
      However, Western blot analysis revealed no changes in the p53 or p21 levels in BA
      treated cells, suggesting that BA might mediate its action via a non-p53 pathway.
      These data indicate that BA may have an application as a chemopreventive agent in
      patients with congenital naevi.

PMID- 11333134
TI  - Oral antifungals as prophylaxis in haematological malignancy.
AB  - In the standard treatment of patients with haematological malignancy,
      immunosuppressive therapy produces prolonged periods of neutropenia and
      mucositis, which increase the risk of systemic fungal infection. In allogeneic
      bone marrow transplantation, this risk extends well beyond the period of
      neutropenia when graft-versus-host disease, and its treatment, result in
      prolonged lymphocytopenia. Various agents are used for antifungal prophylaxis and
      treatment but all have limitations: amphotericin B is restricted by the need for
      intravenous infusion and the occurrence of adverse events, fluconazole by its
      narrow spectrum of activity and the emergence of fluconazole-resistant fungi and
      itraconazole capsules by erratic absorption. Oral administration of antifungals
      has clear advantages in prophylaxis and an important current strategy is to
      maximize the extent and reliability of the oral bioavailability of antifungal
      agents. Mucositis is the main obstacle for success of strategies based on oral
      delivery. In this review, the ability of these new oral formulations to deliver
      sufficient antifungal prophylaxis is evaluated.

PMID- 11333135
TI  - Anemia and aging: an overview of clinical, diagnostic and biological issues.
AB  - Anemia, usually mild, is one of the more common problems of the aged, especially
      in men. Although the anemia is often multifactorial, the specific entities can be
      grouped into three broad categories: (a) anemias due to causes more common in the
      elderly; (b) anemias without special predilection for the elderly; (c) anemias of
      unknown cause. The major biological questions concern the third category, which
      accounts for 14-17% of the anemias, and whether senescence itself contributes to
      anemia. Current opinion favors a diminished erythropoietic reserve with aging,
      but the data are inconsistent and the mechanism has not been established. It may
      be that cytokine modulation of erythropoiesis is abnormal. Some findings in
      unexplained anemia bear partial resemblance to the changes of anemia of chronic
      disease, suggesting the possibility that subtle unidentified inflammatory
      responses of unknown origin may be operative in many elderly people. Of the
      anemias of known cause that are especially common in the elderly, anemia of
      chronic disease is an important entity but is sometimes obscured or overlooked
      and its diagnosis rests on crude tests. Cobalamin deficiency is very common also,
      although most cases are mild and not accompanied by anemia. Because the basic
      diagnostic approach to anemia is neither complex nor very invasive and anemia may
      be a marker of poor prognosis, attribution of anemia to senescence is not
      advisable until other causes have been ruled out.

PMID- 11333137
TI  - Acquired thrombophilic syndromes.
AB  - As the biochemical mechanisms of hypercoagulable states are revealed, the
      syndromes of venous thromboembolism have been increasingly associated with
      specific aberrations. Most of these changes involve an increase in procoagulant
      potential, for example, by activation of the coagulation cascade, or by a defect
      or decrease in natural inhibitors of clotting. Similar abnormalities of the
      fibrinolytic pathways may contribute, as can loss of inhibitory mechanisms of
      endothelial cells, as well as changes in vascular anatomy and rheologic patterns
      of blood flow. All of these factors can directly influence thrombus formation
      and/or the physiologic response to the thrombus.(1)

PMID- 11333136
TI  - Genetic diseases of hemoglobin: diagnostic methods for elucidating beta
      thalassemia mutations.

PMID- 11333138
TI  - The detection and significance of chromosomal abnormalities in childhood acute
      lymphoblastic leukaemia.
AB  - In childhood acute lymphoblastic leukaemia (ALL), cytogenetics plays an essential
      role in diagnosis and prediction of outcome. Conventional cytogenetic analysis,
      complemented by fluorescence in situ hybridization (FISH), is highly effective in
      the accurate detection of chromosomal abnormalities. For the precise
      identification of specific genetic changes, molecular techniques may be applied.
      Chromosomal changes in ALL may be of structural or numerical type. A large number
      of established structural chromosomal rearrangements have now been described for
      which the genetic alterations and effect on prognosis are well known. These
      include t(9;22)(q34;q11) and BCR/ABL, rearrangements of 11q23 involving MLL,
      t(12;21)(p13;q22) with the ETV6/AML1 fusion, t(1;19)(q23;p13) with E2A/PBX1,
      t(8;14)(q24;q32) and the immunoglobulin genes. Genetic changes associated with T
      ALL are also known, although their effect on outcome is less pronounced. Rare
      chromosomal abnormalities are continually being discovered in small patient
      subgroups leading to the identification of new ALL associated genetic changes.
      Alterations in chromosome number have a strong impact on outcome in childhood
      ALL. The association of a high hyperdiploid karyotype (51-65 chromosomes) with a
      good prognosis has been known for more than 20 years. Conversely, the loss of
      chromosomes in the near-haploid group (23-28 chromosomes) indicates a poor
      outcome. New methods of cancer classification involving gene expression profiling
      may eventually supercede cytogenetic analysis in the diagnosis and prediction of
      outcome in leukaemia. It is more likely that they will be used in a complementary
      approach alongside cytogenetic, FISH and molecular analysis to guide patient
      management in childhood ALL.

PMID- 11333139
TI  - Influence of tumor necrosis factor-alpha on the ability of monocytes and
      lymphocytes to destroy intraerythrocytic Plasmodium falciparum in vitro.
AB  - It has been shown that administration of TNF-alpha causes an increase of survival
      of plasmodium-infected mice. However, this anti-parasitic effect cannot be
      reproduced in vitro upon direct incubation of the cytokine with the parasite.
      This suggests that TNF-alpha may act through modulation of some plasmodicidal
      mechanism not yet clarified. We evaluated the effect of exogenous TNF-alpha on
      the phagocytosis of Plasmodium falciparum-infected erythrocytes by monocytes and
      its influence on the ability of monocytes and lymphocytes to inhibit parasite
      growth. The capacity of endogenous TNF-alpha to influence the ability of
      monocytes to inhibit the parasite was also verified. We found that addition of 33
      ng TNF-alpha/mL to cultures of human monocytes and P. falciparum-infected
      erythrocytes increased the phagocytic index from 3.8 to 7.8 in the presence of
      serum containing P. falciparum antibody. TNF-alpha increased the capacity of
      monocyte plus lymphocyte to inhibit parasite growth by about 3 times at 0.5 and 5
      ng/mL. Sera from severely ill P. falciparum-infected individuals inhibited the
      parasite growth, but addition of anti-TNF-alpha antibody was unable to modify
      this inhibition. These data show that TNF-alpha can increase the phagocytic
      capacity. This was probably due to an increased expression of Fc receptors on
      monocytes or to the modulation of Fc receptor signaling pathways by signals
      originating from the binding of TNF-alpha to its receptors. TNF-alpha also acted
      on lymphocytes plus monocytes by increasing the inhibition of P. falciparum by a
      mechanism not related to phagocytosis. These findings suggest that TNF-alpha has
      a pleiotropic anti-malaria effect and that this protective effect depends on the
      interplay of different factors, such as monocytes/macrophages, lymphocytes, and
      antibodies, in addition to other cells and molecules.

PMID- 11333140
TI  - Veto activity of activated bone marrow does not require perforin and Fas ligand.
AB  - Veto cells suppress generation of CD8(+) T cell immune responses in an antigen
      specific manner, with specificity dictated by antigens on the veto cell surface.
      Activated bone marrow (ABM) veto cells belong to the NK cell type lineage and
      veto by clonally deleting antigen-specific precursor cytotoxic T cell lymphocyte
      (CTL). In vitro cytotoxicity of ABM depends largely on the perforin/granzyme and
      Fas/Fas ligand pathways. Utilizing perforin-deficient and functional Fas ligand
      deficient gld mice as a source of ABM and functional Fas-deficient lpr mice as a
      source of precursor CTL, we demonstrate in this study that ABM cells utilize a
      perforin- and Fas-independent pathway to veto allogeneic cell-mediated cytotoxic
      responses. We also show that ABM cells mediate perforin- and Fas-independent veto
      activity even in an 8-h clonal deletion assay. We conclude that ABM veto activity
      does not require the two primary pathways of cell-mediated death.

PMID- 11333141
TI  - IL-7 prevents both caspase-dependent and -independent pathways that lead to the
      spontaneous apoptosis of i-IEL.
AB  - Intestinal intraepithelial lymphocytes (i-IEL) readily undergo spontaneous
      apoptosis in vitro through an unclear mechanism. Here we examined the
      relationship between caspases, which plays a major role in apoptosis, and IL-7 in
      the spontaneous apoptosis of i-IEL in vitro. We demonstrated that IL-7 and zVAD
      prevented the spontaneous apoptosis of i-IEL by approximately 50% and 25%
      respectively with no additive protection seen when both are used. IL-7
      preferentially prevented the apoptosis of gammadelta i-IEL, while zVAD equally
      prevented the apoptosis of gammadelta and alphabeta i-IEL. Lastly, we
      demonstrated that the spontaneous apoptosis of i-IEL is associated with a marked
      increase in caspase activity. Caspase activity was completely inhibited by zVAD,
      but only slightly by IL-7. Overall these results suggest that two pathways lead
      to the spontaneous apoptosis of i-IEL, one which is caspase dependent and the
      other which is caspase independent. IL-7 appears to exert its effect on i-IEL
      undergoing spontaneous by partially inhibiting both apoptotic pathways.

PMID- 11333142
TI  - Adhesion of neutrophils to fibronectin: role of the cd66 antigens.
AB  - Adhesion of neutrophils to substrate is initiated by receptor-ligand interactions
      that induce outside-in signaling. Inside-out signals and lateral interactions
      between surface molecules further fine tune the response. This study investigates
      the role of CD66 in adhesion of neutrophils to fibronectin, using domain-mapped
      monoclonal antibodies to CD66. Neutrophils express CD66a, CD66b, and CD66c on
      their surface. The neutrophil surface molecules that bind to fibronectin are the
      alpha(4)beta(1) and alpha(5)beta(1) integrins. Our results show that the
      monoclonal antibody Kat4c, which recognizes the AB domain of CD66a, b, and c and
      the polyclonal anti-CD66 (anti-carcinoembryonic antigen), augments neutrophil
      adhesion to fibronectin, while monoclonal antibodies to the individual CD66
      antigens, the Fab fragment of Kat4c, and a mixture of the individual antibodies
      to CD66 antigens were unable to affect the adhesion. Thus heterodimerization of
      CD66a, b, and c is required for promoting neutrophil adhesion to fibronectin. The
      increased adhesion in presence of Kat4c was inhibited by antibodies to the
      beta(1) and beta(2) integrins. Antibody ligation of CD66 antigens causes their
      clustering and concomitant coclustering of the alpha(M) subunit of the beta(2)
      integrin, thereby activating the integrin. The sugar alpha-methyl mannoside
      inhibited anti-CD66-mediated clustering, indicating that a carbohydrate-lectin
      interaction may exist between CD66 and alpha(M) integrin. It also reduced the
      increased adhesion of neutrophils to fibronectin, suggesting that beta(2)
      integrin activation precedes beta(1) integrin activation. Further, the anti-CD66
      mediated adhesion to fibronectin is accompanied by increased localization of Src
      family kinases (lyn and hck) to the cytoskeleton and an increase in their kinase
      activity. These results suggest that crosslinking of CD66a, CD66b, and CD66c
      promotes activation of the beta(2) integrin and in turn an alteration in the
      affinity of the beta(1) integrin, which enhances the adhesion of neutrophils to
      fibronectin.

PMID- 11333143
TI  - Prevention and reversal of experimental autoimmune myasthenia gravis by a
      monoclonal antibody against acetylcholine receptor-specific T cells.
AB  - We have recently described an algorithm to design, among others, peptides with
      complementarity contour to autoimmune epitopes. Immunization with one such
      peptide resulted in a monoclonal antibody (mAb), termed CTCR8, that specifically
      recognized Vbeta15 containing TCR on acetylcholine receptor (AChR) alpha-chain
      residue 100-116-specific T cells. CTCR8 was found to label the cell surface of
      AChR100-116-specific T cell lines and clones, immunoprecipitate the TCR from such
      cells, and block their proliferative responses to AChRalpha100-116. In the
      present report, we have found that there is a marked reduction in IFN-gamma and
      no effect on IL-10 production in a CTCR8-treated AChRalpha100-116-specific T cell
      line. Interestingly, when AChR100-116-primed, primary T cells were stimulated
      with peptide and treated with CTCR8, there was once again inhibition of IFN-gamma
      but also marked stimulation of IL-10 production. The change in the Th1/Th2
      cytokine profile was paralleled by a reduction in AChR-specific IgG2a and IgM
      with no effect on IgG1. Remarkably, the most profoundly inhibited Ab population
      was that which causes experimental autoimmune myasthenia gravis (EAMG) by
      reaction with the main immunogenic region (alpha61-76) of the AChR. Based on
      these results, CTCR8 was tested for prophylactic and therapeutic effects in EAMG.
      EAMG induced by immunization with purified native Torpedo AChR was both inhibited
      and reversed by CTCR8. These findings suggest a means to produce therapeutic mAb
      for the treatment of autoimmune diseases.

PMID- 11333144
TI  - Regulation of T cell cytokine production by dendritic cells generated in vitro
      from hematopoietic progenitor cells.
AB  - When dendritic cells (DC) present antigens to T cells, reciprocal cellular
      interactions occur that lead to cytokine production. This cytokine response is
      regulated by specific properties of DC, notably their maturation/activation
      status and perhaps their origin. The latter possibility prompted us to determine
      if DC produced along distinct developmental pathways induced distinct T cell
      responses. Hematopoietic progenitor cells with the potential to differentiate
      into multiple lineages of cells were induced to differentiate into DC along two
      pathways. One leads to the formation of lymphoid-related DC but not of monocyte
      derived DC and is induced by culture of CD34(+) cells with flt-3 ligand (F), c
      kit ligand (K), GM-CSF (Gm), IL-1beta ("1"), and IL-7 ("7") (FKGm17). Another
      pathway with distinct molecular requirements supports in part monocyte-derived DC
      and is induced by the cytokines F, K, Gm, TNF-alpha (T), and IL-4 ("4") (FKGmT4).
      DC produced along these two pathways were isolated by flow cytometry and
      compared. They differed only slightly in phenotype and morphology and both
      induced Th1-type cytokine production in MLR (mixed lymphocyte reactions).
      However, on a cell-per-cell basis, FKGm17-DC produced more IL-18 or IL-12 and
      induced more IFN-gamma by T cells in MLR. Such superior properties were not
      intrinsically determined by the origin of the DC but were induced by FKGm17
      cytokines. We conclude that lymphoid-related DC have the potential to induce Th1
      T cell responses but that environmental signals strongly influence T-cell
      stimulating properties of DC.

PMID- 11333145
TI  - Early cellular events in systemic autoimmunity driven by chromatin-reactive T
      cells.
AB  - In vivo exposure of the thymus of normal mice to procainamide-hydroxylamine, a
      lupus-inducing drug, causes development of chromatin-reactive T cells.
      Autoantibodies subsequently appear, but their origin and significance are
      unknown. The current studies were undertaken to determine the specificities of B
      cells that respond to chromatin-reactive T cells at the initiation of this
      autoimmune process. Three days after adoptive transfer of 6 x 10(6) chromatin
      reactive T cells, B cells with the capacity to secrete IgM anti-chromatin
      antibodies were detected in 1/10(6) splenocytes, and these became 10- to 50-fold
      more numerous if either the donor T cells or the recipient had defective Fas due
      to the lpr allele. Five days later these mice developed IgG anti-chromatin
      secreting B cells at a precursor frequency of 3-6 x 10(-5). B cells with dDNA
      binding activity isolated from mice primed in vivo to a complex of methylated
      pigeon cytochrome c and dDNA could stimulate naive, cytochrome c-reactive T cells
      in vitro, demonstrating that B cells can internalize dDNA-bound proteins through
      their dDNA immunoblobulin receptor and can functionally present a T cell epitope.
      However, no capacity of chromatin for binding anti-dDNA antibodies was detected,
      and IgM dDNA-specific B cells did not expand when challenged with chromatin
      reactive T cells in vivo. The rapid and robust expansion of anti-chromatin
      secreting B cells indicates that the normal immune repertoire includes
      nontolerant autoreactive B cells that respond to strong T cell drive and are
      readily manifested if Fas-mediated activation-induced cell death is inhibited.

PMID- 11333146
TI  - Specific immunotherapy of experimental myasthenia gravis in vitro: the "guided
      missile" strategy.
AB  - We describe a strategy for specific immunotherapy of myasthenia gravis (MG) based
      on genetic engineering of antigen presenting cells (APCs) to present the
      autoantigen acetylcholine receptor (AChR) and express the "warhead" Fas ligand
      (FasL). For transduction of APCs we prepared recombinant attenuated vaccinia
      virus vectors carrying the following three gene constructs: (i) AChR fused to
      LAMP1 to present AChR and target AChR-specific T cells; (ii) FasL to eliminate
      the targeted T cells; and (iii) truncated FADD to protect APCs from self
      destruction by FasL. The engineered APCs effectively expressed the genes of
      interest and killed AChR-specific T cells in culture by the Fas/FasL pathway. T
      cells specific for an unrelated antigen were spared. Our in vitro demonstration
      that engineered APCs target and kill antigen-specific T cells represents a
      promising novel strategy for specific immunotherapy of MG and other autoimmune
      diseases.

PMID- 11333147
TI  - DNA methylation and carcinogenesis.
AB  - In the world of easy things truth is opposed to lie; in the world of complicated
      things one profound truth is opposed to another not less profound than the first.
      Neils Bohr The hypothesis of the exclusively genetic origin of cancer ("cancer is
      a disease of genes, a tumor without any damage to the genome does not exist")
      dominated in the oncology until recently. A considerable amount of data
      confirming this hypothesis was accumulated during the last quarter of the last
      century. It was demonstrated that the accumulation of damage of specific genes
      lies at the origin of a tumor and its following progression. The damage gives
      rise to structural changes in the respective proteins and, consequently, to
      inappropriate mitogenic stimulation of cells (activation of oncogenes) or to the
      inactivation of tumor suppressor genes that inhibit cell division, or to the
      combination of both (in most cases). According to an alternative (epigenetic)
      hypothesis that was extremely unpopular until recently, a tumor is caused not by
      a gene damage, but by an inappropriate function of genes ("cancer is a disease of
      gene regulation and differentiation"). However, recent studies led to the
      convergence of these hypotheses that initially seemed to be contradictory. It was
      established that both factors--genetic and epigenetic--lie at the origin of
      carcinogenesis. The relative contribution of each varies significantly in
      different human tumors. Suppressor genes and genes of repair are inactivated in
      tumors due to their damage or methylation of their promoters (in the latter case
      an "epimutation", an epigenetic equivalent of a mutation, occurs, producing the
      same functional consequences). It is becoming evident that not only the mutagens,
      but various factors influencing cell metabolism, notably methylation, should be
      considered as carcinogens.

PMID- 11333148
TI  - 3alpha-Hydroxysteroid dehydrogenase in animal and human tissues.
AB  - This review analyzes data on the biological role of 3alpha-hydroxysteroid
      dehydrogenase (3alpha-HSD) in animal and human tissues and describes its main
      characteristics, mechanism of action, and regulation of activity. Based on
      published data, a scheme for the actions of androgen, progestin, and
      glucocorticoids involving the participation of 3alpha-HSD is proposed. According
      to this scheme, in the mechanism of steroid action 3alpha-HSD not only regulates
      the concentration of the main effector androgen, 5alpha-dihydrotestosterone, in
      target cells, but also switches androgen, progestin, and glucocorticosteroid
      genomic activity to non-genomic activity.

PMID- 11333149
TI  - alpha-Glucosidases.
AB  - This review highlights the main properties of mammalian, plant, and microbial
      alpha-glucosidases. Special attention is given to the classification of these
      enzymes, possible catalytic mechanisms, their tertiary structure, and the
      structure of major inhibitors. Experimental data on the elucidation of amino acid
      residues essential for catalysis are also discussed.

PMID- 11333150
TI  - Luminol-dependent chemiluminescence analysis of chitooligosaccharide-induced
      rapid production of hydrogen peroxide by intact wheat seedlings.
AB  - The feasibility of a luminol-dependent chemiluminescence analysis of hydrogen
      peroxide production by intact wheat seedlings using a KhL-003 chemiluminometer
      was determined. It was shown that the minimal H2O2 concentration that can be
      detected in a 0.5-ml sample with this instrument is 0.125 microM. Analysis of
      biological activity of a mixture of chitooligosaccharides with molecular masses
      from 5 to 10 kD and acetylation degree of 65% demonstrated that, at a
      concentration of 1 microg/ml, they induce rapid overproduction of H2O2 in roots
      of 3-day-old wheat seedlings.

PMID- 11333151
TI  - Chitooligosaccharide-induced activation of o-phenylenediamine oxidation by wheat
      seedlings in the presence of oxalic acid.
AB  - A method for determination of oxidation of phenolic compounds by intact wheat
      seedlings using o-phenylenediamine (OPD) was developed. The reaction is initiated
      by the addition of oxalic acid to the incubation medium. It is suggested that an
      endogenous peroxidase and hydrogen peroxide formed during oxidation of oxalic
      acid by endogenous oxalate oxidase are involved in OPD oxidation. Treatment of
      plants with chitooligosaccharides (1-10 mg/liter) with acetylation degree of 65%
      and molecular masses of 5-10 kD significantly activated OPD oxidation by wheat
      seedlings.

PMID- 11333152
TI  - Impact of MK-886 on H2O2 generation by human neutrophils and cell degranulation.
AB  - Metabolic inhibitors can clearly affect different aspects of the functional
      activity of cells. This property was studied in the present work with respect to
      MK-886, a well-known inhibitor of the 5'-lipoxygenase-activating protein. It was
      found that this inhibitor in a micromolar concentration range (2-20 microM)
      induced in a dose-dependent manner H2O2 generation by human neutrophils and the
      release of lysozyme from the cells. The MK-886-induced activation of neutrophils
      was accompanied by a significant decrease in N-(1-pyrene)maleimide-accessible SH
      groups in the cells. According to its activity, MK-886 can be considered an
      agonist that causes up-regulation of inherent neutrophil functions. In summary,
      the results indicate that during the application of MK-886 as a 5;-lipoxygenase
      inhibitor in neutrophils, the impact of the compound on the functional activity
      of the cells should be taken into consideration.

PMID- 11333153
TI  - Study on conformational changes in hemoglobin protoporphyrin in essential
      hypertension.
AB  - Changes in protoporphyrin conformation, partial pressures of O2 and CO2, and the
      mechanisms responsible for regulation of pCa and pH in erythrocytes were studied
      in essential hypertension (EH). Changes in protoporphyrin conformation in EH were
      accompanied by a decrease in the partial pressure of O2 and an increase in the
      partial pressure of CO2. This was associated with increased activities of Na+/H+
      exchange and Ca2+-dependent K+-channels and with a decreased activity of Ca2+
      ATPase. The changes in protoporphyrin conformation in EH are suggested to
      decrease the efficiency of O2 metabolism in hemoglobin and increase the values of
      intracellular pCa and pH of erythrocytes.

PMID- 11333154
TI  - On the ability of high density lipoproteins to remove phospholipid peroxidation
      products from erythrocyte membranes.
AB  - To study the transfer of oxidized phospholipids from cell membranes to high
      density lipoproteins (HDL), human Cu2+-oxidized erythrocyte membranes were
      incubated with HDL3 subfraction for 17 h at 37 degrees C followed by isolation of
      the supernatant, precipitation from it of HDL3, and determination of lipid
      peroxide products (LPP) in them. The incubation increased the content of lipid
      hydroperoxides in HDL3 significantly (by 32 and 40% calculated per ml of sample
      or mg of protein) and of malondialdehyde (by 27 and 34%, respectively) compared
      to control (incubation of HDL3 alone). The content of conjugated dienes did not
      change significantly. Fluorescence analyses of isolated HDL3 particles showed
      that the content of fluorescent products (lambdaex = 365 nm, lambdaem = 430 nm)
      in them was 2.5 times higher than in control, and the number of binding sites for
      the 1-anilinonaphthalene-8-sulfonic acid probe decreased by 22%. This also
      confirms accumulation of LPP in the lipoprotein subfraction. It seems likely that
      an increase in LPP (at least hydroperoxides) in HDL3 after their incubation with
      oxidized membranes occurs via transport of phospholipids containing LPP from
      erythrocyte membranes to lipoproteins. The data on the ability of HDL3 to accept
      LPP from erythrocyte membranes in vitro suggest that HDL3 may have a protective
      action on cell membranes undergoing oxidation in vivo as well.

PMID- 11333155
TI  - Changes in cytokinin distribution in the ovule and ovary of Taraxacum officinale
      Web. in early stages of embryogenesis.
AB  - Quantitative changes in the hormonal status of the ovules and ovaries were first
      studied in Taraxacum officinale Web. at the early stages of embryogenesis. The
      plant material was analyzed by ELISA using labeled anti-rabbit antibodies. A new
      procedure for differential and quantitative determination of the main endogenous
      cytokinins based on the estimation of the effective zeatin and zeatin riboside
      concentrations from calibration curves constructed using zeatin and zeatin
      riboside as standard antigens was developed. It was shown that, at the three
      initial stages of embryogenesis examined, the concentration of zeatin uniformly
      increased in T. officinale ovules. The concentration of zeatin riboside,
      conversely, uniformly decreased. However, their total concentration changed
      insignificantly. A gradual increase in the concentration of the active and
      storage hormone forms from the ovary to the ovule was shown.

PMID- 11333156
TI  - Experimental and theoretical investigation of arachidonic acid uptake in
      macrophages.
AB  - The kinetics of 3H-labeled arachidonic acid (AA, 10(-10)-10(-5) M) incorporation
      into murine peritoneal macrophages was investigated. During the incorporation of
      AA into the cells, the steady state was reached at 10 h. The level of
      incorporation consisted of 48-50% for nanomolar concentrations and 28-30% for
      micromolar concentrations of AA. Exogenous AA in micromolar but not nanomolar
      concentrations stimulated [3H]AA release from intracellular stores of pre-labeled
      cells. A mathematical model fitting the behavior of the experimental system is
      proposed. The difference in the level of uptake of AA in nanomolar and micromolar
      concentrations is explained by the activation of AA release from intracellular
      stores at high concentrations of exogenous AA.

PMID- 11333157
TI  - Interaction of the bacterial ribonuclease binase with the polypeptide inhibitor
      barstar based on kinetic data on poly(U) hydrolysis.
AB  - The reaction of poly(U) hydrolysis catalyzed by binase while the latter is
      inhibited by barstar has been investigated. The inhibition constant for barstar
      and the apparent Michaelis constants for the inhibition by barstar in the
      presence of ethanol and NaCl have been determined. Both ethanol and NaCl enhance
      the inhibition by barstar. This suggests that the binding of barstar with binase
      is probably due to the interaction of hydrophobic sites rather than by
      electrostatic interaction between amino acid residues.

PMID- 11333158
TI  - Study of the mechanism of action of p-chloromercuribenzoate on endonuclease from
      the bacterium Serratia marcescens.
AB  - The mechanism of action of p-chloromercuribenzoate (PCMB) on Serratia marcescens
      nuclease was investigated. The analysis showed that PCMB forms complexes with
      DNA. Binding of C7H5O2Hg+ to DNA changes the secondary structure of the DNA.
      These changes alter the enzymatic activity of S. marcescens nuclease, which was
      previously found to be sensitive to the secondary structure of the substrates.
      The nuclease activity was either suppressed or stimulated in the presence of PCMB
      depending on the C7H5O2Hg+ to nucleotide equivalent ratio. Binding of C7H5O2Hg+
      to DNA did not form an abortive enzyme-substrate complex. Binding of Mg2+ to the
      C7H5O2Hg-DNA complex caused appropriate changes in secondary structure of the
      substrate. Since Mg2+ and C7H5O2Hg+, though differing in the type of metal
      cation, are similar in their mechanisms of influence on enzymatic activity of S.
      marcescens nuclease, the identity of other metal-containing effectors in their
      mechanism of action on Serratia marcescens nuclease is assumed.

PMID- 11333159
TI  - Allopurinol enhances adenine nucleotide levels and improves myocardial function
      in isolated hypoxic rat heart.
AB  - Allopurinol, a competitive inhibitor of xanthine oxidase, was found to have a
      protective effect on ischemic myocardium. Its mechanism of action is still
      controversial. We used Langendorff isolated rat heart preparation to test the
      hypothesis that allopurinol could maintain a level of the adenine nucleotide pool
      (ATP, ADP, and AMP) that would protect and improve the functional activity of the
      heart during a period of hypoxia. Hearts were initially perfused for 30 min until
      steady state was attained. This was followed by 20 min of experimental perfusion
      divided into 5 min of control perfusion followed by 15 min of hypoxic perfusion
      with or without allopurinol in the perfusate. Hearts were quick-frozen and
      enzymatically analyzed for adenine nucleotides and creatine phosphate at the end
      of the hypoxic period. Left ventricular pressure, heart rate, and coronary flow
      were measured in all preparations. Allopurinol (0.1 mM) treated hearts had
      greater levels of ATP (12.3 +/- 0.8 vs. 9.3 +/- 0.8 micromol/g dry weight; p <
      0.01). This improvement occurred in the presence as well as the absence of
      glucose. Total adenine nucleotides improved from 17 +/- 1 to 20.3 +/- 2.4
      micromol/g dry weight (p < 0.01). This improvement also occurred in the presence
      as well as in the absence of glucose in the perfusate. It also improved cell
      energy state significantly in the presence as well as the absence of glucose.
      There was insignificant change in creatine phosphate. Allopurinol improved left
      ventricular pressure from 38 +/- 7% to 55 +/- 9% (p < 0.002) in the presence of
      glucose and from 8 +/- 3% to 27 +/- 6.3% (p < 0.001) in the absence of glucose.
      Coronary flow improved from 110 +/- 5% to 120 +/- 8% (p < 0.04) in the presence
      of glucose. These results support the suggestion that allopurinol at 0.1 mM
      exerts its protective effect on rat heart during hypoxia by enhancing the adenine
      nucleotide pool.

PMID- 11333160
TI  - Identification of catalytically active groups of Penicillium canescens F-436 beta
      galactosidase.
AB  - The functional groups of Penicillium canescens F-436 beta-galactosidase have been
      identified. The pK values and heats of ionization of these groups and
      photoinactivation of the enzyme with methylene blue indicate that the active site
      contains carboxyl and imidazole groups. A mechanism for the participation of
      these groups in the cleavage of the glycoside bond in lactose is proposed.

PMID- 11333161
TI  - Complexing of basic pancreatic proteinase inhibitor with soybean phospholipid
      multilamellar vesicles.
AB  - The formation of complexes of basic pancreatic proteinase inhibitor (BPTI) with
      multilamellar vesicles (MLV) from six preparations of soybean phospholipids of
      various composition was studied. When BPTI, a non-membrane protein, interacts
      with MLV, the vesicles aggregate, forming a precipitate of protein-lipid
      complexes. The BPTI content in the protein-lipid complexes increases with
      decreasing pH of the medium and on addition of negatively charged components into
      the lipid mixture. The protein-induced aggregation of the phospholipid vesicles
      is suggested to be mainly determined by electrostatic forces. The antiproteinase
      activity of BPTI in the complexes was rather low but increased up to 70% of the
      initial activity on addition of an ionic detergent (sodium deoxycholate).

PMID- 11333162
TI  - A phosphodiesterase from ascites carcinoma Krebs II cells specifically cleaves
      the bond between VPg and RNA of encephalomyocarditis virus.
AB  - The substrate specificity of the "unlinking" enzyme from ascite carcinoma Krebs
      II cells has been investigated. The enzyme specifically splits the interpolymeric
      phosphodiester bond between Kp and the 5;-terminal phosphate group of the
      uridylic acid residue in the Kp-pUpUpGp complex.

PMID- 11333163
TI  - Atrial fibrillation: is rate stabilization a valid clinical strategy?

PMID- 11333164
TI  - The effect of myocardial surgical revascularization on left ventricular late
      potentials.
AB  - BACKGROUND: The presence of ventricular late potentials (LP) is an important
      indicator for the development of ventricular tachyarrhythmias due to ischemic
      heart disease. The effect of myocardial revascularization on LP has remained
      controversial. The purpose of this study was to determine whether complete
      myocardial surgical revascularization (CABG) documented by myocardial perfusion
      scintigraphy might alter the substrate responsible for LP. METHODS:
      Prospectively, enrolled patients undergoing elective CABG were evaluated with
      thallium-201 myocardial perfusion scintigraphy and signal- averaged ECG pre- and
      postoperatively. SAECG recordings were obtained serially: before, 48-72 hours and
      3 months after CABG. LPS were defined as positive if SAECG met at least two of
      Gomes criteria. Scintigraphies were performed pre- and 3 months postoperatively
      for determination of the success of revascularization. Changes observed in SAECG
      recordings after CABG were compared between those with and without successful
      revascularization. RESULTS: CABG resulted in successful revascularization in 23
      patients and was unsuccessful in 17 (no change or deterioration of the perfusion
      defects). Preoperative SAECG values were not different between groups except for
      RMS values. The incidence of LP decreased significantly postoperatively in
      patients with improved myocardial perfusion, whereas there were no changes in
      patients who did not have postoperative perfusion improvement (McNemar test, P <
      0.05). CONCLUSIONS: LPs disappear following the elimination of myocardial
      ischemia by complete surgical revascularization. Persistence of ischemia
      following CABG usually results in the persistence of late potentials. The
      incidence of ventricular arrhythmias is expected to be unchanged in these
      patients and they should be reevaluated for reinterventions.

PMID- 11333165
TI  - Circadian behavior of P-wave duration, P-wave area, and PR interval in healthy
      subjects.
AB  - BACKGROUND: The prolongation of P-wave duration has long been shown to indicate
      the presence of high risk for atrial fibrillation. The circadian variation of P
      wave characteristics and their dynamic adaptation to heart rate changes was not
      tested before. METHODS: To evaluate the diurnal pattern of P-wave duration, P
      area, and PR interval and of their linearly fitted relation with RR interval, 50
      healthy volunteers (25 men, mean age 34 +/- 10 years) underwent 24-hour
      ambulatory electrocardiographic (ECG) recording with digital 12-lead Holter
      recorders. The median P-wave duration, P area, and PR interval were calculated
      from the average 12-lead ECG constructed from each 10-second ECG recording.
      Single harmonic regression analysis was performed to reveal the presence of
      circadian variation in the aforementioned ECG parameters. RESULTS: The P area (P
      < 0.0001, R(2) = 0.78), the PR interval (P < 0.0001, R(2) = 0.92), the P area /
      RR slope (P < 0.0001, R(2) = 0.55), and the PR/RR slope (P < 0.0001, R(2) = 0.42)
      showed a highly significant circadian variation while the periodic nature of P
      wave duration (P = 0.016, R(2) = 0.32) and of the P duration / RR slope (P =
      0.011, R(2) = 0.18) was only indicated by harmonic regression analysis.
      CONCLUSIONS: P-wave duration, P area, and PR interval show a significant
      circadian variation in healthy subjects. The relations between P area/RR,PR/ RR,
      and P duration/RR also demonstrate a significant diurnal pattern.

PMID- 11333166
TI  - Effect of beta-blockade on autonomic modulation of heart rate and neurohormonal
      profile in decompensated heart failure.
AB  - BACKGROUND: One of the putative mechanisms for the salutary effects of beta
      blockers in patients with congestive heart failure (CHF) is their ability to
      improve autonomic dysfunction. However, patients with profound neurohumoral
      abnormalities derive little survival benefit from beta-blockers. The purpose of
      the current study was to evaluate the effect of beta-blockers on heart rate
      variability (HRV) in decompensated CHF. METHODS: Time and frequency domain HRV
      indices were obtained from 24-hour Holter recordings and compared to assess the
      role of beta-blockade in 199 patients (mean age 60 +/- 14 years) with
      decompensated CHF. Neurohormonal differences were assessed by measuring
      norepinephrine, endothelin-1, tumor necrosis factor-alpha, and interleukin-6 in a
      subset of 64 patients. RESULTS: All HRV indices were markedly suppressed but were
      substantially higher in patients who were on beta-blockers. Time domain measures
      of parasympathetic cardiac activity, the percentage of R-R intervals with > 50 ms
      variation (4.9 +/- 0.6 vs 7.7 +/- 1.2%, P = 0.006) and the square root of mean
      squared differences of successive R-R intervals (22.7 +/- 2.0 vs 31.6 +/- 4.1 ms,
      P = 0.004), were higher in the beta-blocker group. Spectral analysis revealed
      that the total power and the ultra-low frequency power were significantly higher
      in patients on beta-blockers (82% and 59%, respectively). The high frequency
      power, a spectral index of parasympathetic modulation, was 41% higher in the beta
      blocker group (121 +/- 25 vs 171 +/- 27 ms(2), P = 0.02). Norepinephrine and
      interleukin-6 levels were substantially lower in patients on beta-blockers (28%
      and 61%, respectively). However, these differences did not reach statistical
      significance. CONCLUSIONS: Beta-blockers improve the impaired cardiac autonomic
      regulation during high sympathetic stress of decompensated CHF. This effect may
      play an important role in protecting the myocardium and preventing arrhythmias
      during transient increases in sympathetic activity.

PMID- 11333168
TI  - Variability in the manifestation of pre-excited atrial fibrillation: its
      quantification, theoretical origin, and diagnostic potential.
AB  - BACKGROUND: Irregular broad complex tachycardia (BCT) may be due to atrial
      fibrillation (AF) occurring in the presence of ventricular pre-excitation (pre
      excited AF) or bundle branch block (BBB-AF). While irregularity is a defining
      characteristic of AF, it is a common subjective impression that greater
      variability in manifestation exists for pre-excited AF than BBB-AF. This
      difference can potentially be exploited for distinguishing the two conditions if
      some means can be found to quantify it. METHODS: For each of 75 ECGs showing
      irregular BCT (41 pre-excited AF and 34 BBB-AF), a random sample of 10 distinct
      QRS complexes were selected for quantitative measurement of variability in
      manifestation, which included the standard deviation (SD) of the width, the SD of
      the axis, and the coefficient of variation (CV) of the amplitude of the QRS
      complex. RESULTS: Pre-excited AF showed statistically significantly greater
      values than BBB-AF with respect to these measures, and receiver-operating
      characteristic curves showed that these differences could be useful for their
      discrimination. For the SD of QRS width, a cut-off value of 8 ms appeared optimal
      (sensitivity 1.00 and specificity 0.79). For the SD of QRS axis, a cut-off value
      of 2.5 degrees appeared optimal (sensitivity 0.84 and specificity 0.56). For the
      CV of QRS amplitude, a cut-off value of 0.10 appeared optimal (sensitivity 0.82
      and specificity 0.76). CONCLUSIONS: Pre-excited AF demonstrated greater
      variability than BBB-AF in manifestation. The measures of variability developed
      can potentially be useful for diagnosing irregular BCT in practice, especially in
      the context of automated computer-aided diagnosis.

PMID- 11333167
TI  - Computerized ST depression analysis improves prediction of all-cause and
      cardiovascular mortality: the strong heart study.
AB  - BACKGROUND: Nonspecific ST depression assessed by standard visual Minnesota
      coding (MC) has been demonstrated to predict risk. Although computer analysis has
      been applied to digital ECGs for MC, the prognostic value of computerized MC and
      computerized ST depression analyses have not been examined in relation to
      standard visual MC. METHODS: The predictive value of nonspecific ST depression as
      determined by visual and computerized MC codes 4.2 or 4.3 was compared with
      computer-measured ST depression >or= 50 microV in 2,127 American Indian
      participants in the first Strong Heart Study examination. Computerized MC and ST
      depression were determined using separate computerized-ECG analysis programs and
      visual MC was performed by an experienced ECG core laboratory. RESULTS: The
      prevalence of MC 4.2 or 4.3 by computer was higher than by visual analysis (6.4
      vs 4.4%, P < 0.001). After mean follow-up of 3.7 +/- 0.9 years, there were 73
      cardiovascular deaths and 227 deaths from all causes. In univariate Cox analyses,
      visual MC (relative risk [RR] 4.8, 95% confidence interval [CI] 2.6-9.1),
      computerized MC (RR 6.0, 95% CI 3.5-10.3), and computer-measured ST depression
      (RR 7.6, 95% CI 4.5-12.9) were all significant predictors of cardiovascular
      death. In separate multivariate Cox regression analyses that included age, sex,
      diabetes, HDL and LDL cholesterol, body mass index, systolic and diastolic blood
      pressure, microalbuminuria, smoking, and the presence of coronary heart disease,
      computerized MC (RR 3.0, 95% CI 1.6-5.6) and computer-measured ST depression (RR
      3.1, 95% CI 1.7-5.7), but not visual MC, remained significant predictors of
      cardiovascular mortality. When both computerized MC and computer-measured ST
      depression were entered into the multivariate Cox regression, each variable
      provided independent risk stratification (RR 2.1, 95% CI 1.0-4.4, and RR 2.1, 95%
      CI 1.0-4.4, respectively). Similarly, computerized MC and computer-measured ST
      depression, but not visual MC, were independent predictors of all-cause mortality
      after controlling for standard risk factors. CONCLUSIONS: Computer analysis of
      the ECG, using computerized MC and computer-measured ST depression, provides
      independent and additive risk stratification for cardiovascular and all-cause
      mortality, and improves risk stratification compared with visual MC. These
      findings support the use of routine computer analysis of ST depression on the
      rest ECG for assessment of risk and suggest that computerized MC can replace
      visual MC for this purpose.

PMID- 11333169
TI  - Optimal target heart rate for exercise-induced T-wave alternans.
AB  - OBJECTIVES: This study was conducted to determine the optimal target heart rate
      (HR) for the use of exercise-induced T-wave alternans (TWA) as an index for risk
      of malignant ventricular tachyarrhythmias. BACKGROUND: Rate-dependent TWA is an
      index of vulnerability to ventricular tachyarrhythmias. However, false positive
      TWA was reported to occur in normal subjects at high HR. METHODS: Two groups were
      evaluated: Group I: 50 patients with malignant ventricular tachyarrhythmias, who
      received an implantable cardioverter-defibrillator (ICD); and Group II: 55 age
      matched normal subjects. In both Groups, TWA was evaluated during symptom-limited
      bicycle exercise test. RESULTS: Peak HR during exercise test was 103 +/- 17
      beats/min in Group I, versus 124 +/- 18 beats/min in Group II (P < 0.001). In
      Group I, 4 patients were excluded from analysis, due to high noise level or
      frequent ectopy during exercise. Out of the remaining 46 patients, TWA was
      present in 28 patients (61%), and absent in 18 (39%). In group II, TWA was
      present in four subjects (7%), and absent in 51 (93%). HR at the onset of TWA was
      91 +/- 11/min in Group I, and 119 +/- 12/min in Group II (P < 0.001). Receiver
      operated characteristics curves demonstrated that a HR of 115 beats/min was the
      cutoff with the best sensitivity and specificity for TWA (100 and 96%,
      respectively). None of the patients in Group I developed TWA at HR > 115
      beats/min, while two out of four in Group II had TWA at HR > 115/minutes.
      However, 13 patients in Group I who had no TWA were unable to exercise to a peak
      HR > 115 beats/min, compared to nine subjects in Group II. CONCLUSIONS: A target
      HR of 115 beats/min was highly sensitive and specific for determination of
      exercise-induced TWA as an index of risk of malignant ventricular
      tachyarrhythmias. However, a significant number of patients may not be able to
      achieve this target HR, resulting in an indeterminate test. The value of
      pharmacologic testing in this group should be assessed.

PMID- 11333170
TI  - An evaluation of the impact of gender and age on QT dispersion in healthy
      subjects.
AB  - OBJECTIVES: To determine if gender, age, and gender per age category, have an
      impact on QT and QTc dispersion in healthy volunteers. METHODS: This study was
      undertaken in 150 patients (50 per age group, 75 males, 75 females). The age
      groups included young (20-40 years), middle-aged (41-69 years) and elderly (> 70
      years) subjects. The QT intervals on a 12 lead ECG were determined and Bazett's
      formula was used to derive the QTc intervals. The QT and QTc dispersion were
      determined by subtracting the shortest QTc interval from the longest on each 12
      lead recording. RESULTS: Males had higher QT dispersion than females (50 +/- 22
      vs 42 +/- 18 ms, P = 0.017) but QTc dispersion was not significantly changed. No
      significant differences were seen among the different age categories for QT or
      QTc dispersion. In elderly subjects, males had higher QT and QTc dispersion than
      females (54 +/- 23 vs 42 +/-15 ms, P = 0.039 and 63 +/- 23.7 vs 48 +/- 21 ms, P =
      0.032, respectively). CONCLUSIONS: When evaluating the effect of gender in
      different age categories, elderly males have significantly greater QT and QTc
      dispersion than elderly female subjects. No other gender differences were noted
      for QT or QTc dispersion in the other two age categories. When evaluating a
      population of healthy volunteers, regardless of age, gender has an impact on QT
      dispersion but no significant interaction with QTc dispersion. Evaluating age
      without dividing the data by gender yields no significant differences in QT or
      QTc dispersion.

PMID- 11333171
TI  - Differences in heart rate dynamics before the spontaneous onset of long and short
      episodes of paroxysmal atrial fibrillation.
AB  - BACKGROUND: Altered heart rate (HR) dynamics precede the spontaneous onset of
      atrial fibrillation (AF), but the factors related to the perpetuation and
      duration of paroxysmal AF episodes are not well established. This study was
      designed to test the hypothesis that HR dynamics preceding the onset of (AF) may
      influence the duration of AF. METHODS: Traditional time and frequency domain HR
      variability indices, along with a short-term fractal scaling exponent (alpha(1))
      and approximate entropy (ApEn), were analyzed in 20-minute intervals before 92
      episodes of spontaneous paroxysmal AF in 22 patients without structural heart
      disease. AF episodes were divided into two groups according to the duration of
      the arrhythmia episodes. RESULTS: The high-frequency (HF) spectral component in
      normalized units (nu) of heart rate variability was higher and low-frequency (LF)
      component lower before long (> 200 s, n = 41) compared to short (< 200 s, n = 51)
      AF episodes (HF nu; 40.1 +/- 14.8 vs 31.5 +/- 16.4, P < 0.0001 and LF nu; 59.9 +/
      14.8 vs 68.5 +/- 16.4, P < 0.0001). Short-term scaling exponent values also were
      lower before long compared to short AF episodes (e.g., alpha(1); 1.12 +/- 0.21 vs
      1.24 +/- 0.23, P < 0.0001). Women had a larger number of long AF episodes than
      men, but the duration of AF was not related to any other clinical or demographic
      features or antiarrhythmic medication. CONCLUSION: Increased HF oscillations and
      decreased short-term correlation properties of R-R intervals, reflecting altered
      sympathovagal balance before the onset of AF, predispose to perpetuation of
      spontaneous arrhythmia episodes in patients with vulnerability to paroxysmal AF
      and without structural heart disease.

PMID- 11333172
TI  - Improving the reproducibility of QT dispersion measures.
AB  - BACKGROUND: The low reproducibility of the QT dispersion (QTD) method is a major
      reason why it is not used in clinics. The purpose of this study was to develop QT
      dispersion parameters with better reproducibility and identification of patients
      with a high risk of ventricular arrhythmia or death. METHODS AND RESULTS: Three
      institutions using different methods for measuring QT intervals provided QT
      databases, which included more than 3500 twelve-lead surface ECGs. The data
      represented low and high risk subjects from the following groups: the normal
      population EpiSet (survivors vs dead from cardiovascular causes), acute
      myocardial infarction patients AmiSet (survivors vs dead) and remote myocardial
      infarction patients ArrSet (with vs without a history of ventricular arrhythmia).
      The EpiSet, AmiSet, and the ArrSet contributed with N = 122, 0, and 110 ECGs for
      reproducibility analysis, and 3244, 446, and 100 ECGs for the analysis of
      prognostic accuracy. The prognostic accuracy was measured as the area under the
      Receiver Operator Curve. The QT intervals were divided into six QT pairs; the
      longest pair consisted of the longest and the shortest QT intervals etc. The QT
      dispersion trend (QTDT) was defined as the slope of the linear regression of the
      N longest QT pairs after estimation of missing QT intervals by interpolation of
      measured QT intervals. The QTMAD and the QTSTD methods were defined as twice the
      mean absolute deviation and the standard deviation of the N longest QT pairs. The
      reproducibility was improved by 27% and 19% in the EpiSet and the ArrSet relative
      to the reproducibility of QTD. The accuracy improved for the EpiSet and the
      ArrSet and was maintained for the AmiSet. CONCLUSIONS: By using the three longest
      and the three shortest QT intervals in QTDT, QTMAD, or QTSTD, the reproducibility
      improved significantly while maintaining or improving the prognostic accuracy
      compared to QTD.

PMID- 11333173
TI  - Normalization of ventricular repolarization with flecainide in long QT syndrome
      patients with SCN5A:DeltaKPQ mutation.
AB  - BACKGROUND: The Long QT Syndrome (LQTS) is a genetic channelopathy with life
      threatening implications. The LQT3 form of this disease is caused by mutations of
      the SCN5A sodium-channel gene. A specific mutation, SCN5A:DeltaKPQ, is associated
      with repetitive reopenings of the sodium channel and prolonged inward current.
      This dominant inward current is manifest on the electrocardiogram as QT
      prolongation. Flecainide is a potent blocker of the open sodium channel. METHODS
      AND RESULTS: The effect of flecainide on the duration of the QT-interval and the
      T-wave morphology was systematically evaluated in five male patients age 2-64
      years having the SCN5A:DeltaKPQ mutation. After baseline electrocardiograms were
      obtained, low-dose oral flecainide was administered for 48 hours. Serial
      electrocardiograms and blood flecainide levels were obtained during flecainide
      therapy. The QTc interval decreased on average by 104 ms, from a baseline value
      of 565 +/- 60 ms to 461 +/- 23 ms (P < 0.04) at a mean flecainide level of 0.28
      +/- 0.08 mg/L, with shortening of the QTonset interval (P < 0.003) and
      normalization of T-wave morphology. The effects of flecainide were compared with
      oral mexiletine in two patients, with flecainide showing greater QTc shortening
      and more complete normalization of repolarization. No adverse side effects or
      proarrhythmia were observed with flecainide in this study. CONCLUSION: Low-dose,
      oral flecainide consistently shortened the QTc interval and normalized the
      repolarization T-wave pattern in five LQT3 patients with SCN5A:DeltaKPQ mutation.
      This preliminary study indicates that low-dose flecainide is a promising
      therapeutic agent for LQTS patients with the SCN5A:DeltaKPQ sodium channel
      mutation.

PMID- 11333174
TI  - P-wave dispersion: a novel predictor of paroxysmal atrial fibrillation.
AB  - BACKGROUND: The prolongation of intraatrial and interatrial conduction time and
      the inhomogeneous propagation of sinus impulses are well known electrophysiologic
      characteristics in patients with paroxysmal atrial fibrillation (AF). Previous
      studies have demonstrated that individuals with a clinical history of paroxysmal
      AF show a significantly increased P-wave duration in 12-lead surface
      electrocardiograms (ECG) and signal-averaged ECG recordings. METHODS: The
      inhomogeneous and discontinuous atrial conduction in patients with paroxysmal AF
      has recently been studied with a new ECG index, P-wave dispersion. P-wave
      dispersion is defined as the difference between the longest and the shortest P
      wave duration recorded from multiple different surface ECG leads. Up to now the
      most extensive clinical evaluation of P-wave dispersion has been performed in the
      assessment of the risk for AF in patients without apparent heart disease, in
      hypertensives, in patients with coronary artery disease and in patients
      undergoing coronary artery bypass surgery. P-wave dispersion has proven to be a
      sensitive and specific ECG predictor of AF in the various clinical settings.
      However, no electrophysiologic study has proven up to now the suspected
      relationship between the dispersion in the atrial conduction times and P-wave
      dispersion. The methodology used for the calculation of P-wave dispersion is not
      standardized and more efforts to improve the reliability and reproducibility of P
      wave dispersion measurements are needed. CONCLUSIONS: P-wave dispersion
      constitutes a recent contribution to the field of noninvasive electrocardiology
      and seems to be quite promising in the field of AF prediction.

PMID- 11333175
TI  - "The auricular wave (P) of the electrocardiogram: clinical observations with
      especial reference to pulmonic and mitral stenoses".

PMID- 11333177
TI  - Issues and practicalities of treating genital warts in the community. Proceedings
      of a round table meeting facilitated by Succinct Communications Limited.

PMID- 11333178
TI  - Solutions to health care waste: life-cycle thinking and "green" purchasing.
AB  - Health care waste treatment is linked to bioaccumulative toxic substances, such
      as mercury and dioxins, which suggests the need for a new approach to product
      selection. To address environmental issues proactively, all stages of the product
      life cycle should be considered during material selection. The purchasing
      mechanism is a promising channel for action that can be used to promote the use
      of environmentally preferable products in the health care industry; health care
      facilities can improve environmental performance and still decrease costs. Tools
      that focus on environmentally preferable purchasing are now emerging for the
      health care industry. These tools can help hospitals select products that create
      the least amount of environmental pollution. Environmental performance should be
      incorporated into the evolving definition of quality for health care.

PMID- 11333179
TI  - Sawmill chemicals and carcinogenesis.
AB  - Workers in wood industries are exposed to variable medleys of chemicals, both
      natural and synthetic. Additional exposures include fungi, bacteria, bark and
      wood dusts, solvents, paints, and various other wood coatings. These individual
      and conglomerate exposures have been associated with diverse occupational
      illnesses and hazards, including cancers. In this commentary, I summarize both
      experimental and epidemiologic carcinogenesis results for several chemicals used
      in the wood industry, as well as for wood dust. Working in the wood industries
      entails excess risks of cancers, among other diseases and workplace injuries. A
      key to preventing occupationally and environmentally associated cancers, as in
      the wood industries, is avoiding exposures to chemicals and wood dusts and, in
      particular, chemicals known to cause cancer in animals or/and humans.

PMID- 11333180
TI  - Metabolites of pyrethroid insecticides in urine specimens: current exposure in an
      urban population in Germany.
AB  - Pyrethroids are important insecticides used in agriculture, forestry,
      horticulture, and in the home. In humans, they are rapidly metabolized and
      renally eliminated. In numerous studies, pyrethroid metabolites have been
      detected in urine after occupational exposure to insecticides. In this study, we
      used a new, reliable, easy, and sensitive analytical method to assess the
      internal pyrethroid exposure of an urban population without exposure to
      pyrethoids at home or at work (children and adults). A total of 1,177 persons
      took part in this investigation, including 331 children under 6 years of age and
      247 children between 6 and 12 years of age. None of them reported exposure to
      pyrethroids at home or at work. Accordingly, the levels of permethrin found in
      household dust from their homes were lower than expected (median < limit of
      detection; 95th percentile, 4.8 mg/kg; maximum value, 19 mg/kg). Urine specimens
      were analyzed for cis-3-(2,2-dibromo-vinyl)-2,2-dimethylcyclo-propanecarboxylic
      acid (Br(2)CA), cis- and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane
      carboxylic acid (cis-Cl(2)CA and trans-Cl(2)CA), and 4-fluoro-3-phenoxybenzoic
      acid (F-PBA) using a gas chromatographic method with mass-selective detection.
      The limit of detection for pyrethroid metabolites was between 0.1 and 0.2
      microg/L. trans-Cl(2)CA was detected in 65% of the urine specimens tested, cis
      Cl(2)CA was detected in 30%, and Br(2)CA and F-PBA were found in 19% and 16%,
      respectively, of the urine specimens. The urinary metabolite levels in children
      did not differ from those in adults, and there was no correlation between the
      levels of metabolites and indoor exposure to permethrin in household dust.
      Moreover, no seasonal correlations could be found. The 95th percentile levels in
      urine specimens were as follows: Br(2)CA, 0.30 microg/L; cis-Cl(2)CA, 0.51
      microg/L; trans-Cl(2)CA, 1.43 microg/L; F-PBA, 0.27 microg/L. Background exposure
      to pyrethroids was found in the general population; it seems to be caused by the
      uptake of pyrethroids with the diet. This hypothesis needs to be tested in
      duplicate diet studies combined with biomonitoring. As long as representative
      data are lacking, however, the rounded 95th percentile values obtained in our
      study may be used as reference values for pyrethroid metabolites in urine samples
      from the population in Germany; 95th percentile values for children and adults
      are as follows: Br(2)CA, 0.3 microg/L; cis-Cl(2)CA, 0.5 microg/L; trans-Cl(2)CA,
      1.5 microg/L; and F-PBA, 0.3 microg/L.

PMID- 11333181
TI  - 1,N(2)-propanodeoxyguanosine adduct formation in aortic DNA following inhalation
      of acrolein.
AB  - Recent reports indicate that many of the cytotoxic and health-threatening
      components of environmental tobacco smoke (ETS) reside in the vapor phase of the
      smoke. We have reported previously that inhalation of 1,3-butadiene, a prominent
      vapor phase component of ETS, accelerates arteriosclerotic plaque development in
      cockerels. In this study we asked whether inhaled acrolein, a reactive aldehyde
      that is also a prominent vapor-phase component of ETS, damages artery-wall DNA
      and accelerates plaque development. Cockerels inhaled 0, 1, or 10 ppm acrolein
      mixed with HEPA-filtered air for 6 hr. Half were killed immediately (day 1 group)
      for detection of the stable, premutagenic 1,N(2)-propanodeoxyguanosine acrolein
      adduct (AdG3) in aortic DNA via a (32)P-postlabeling/HPLC method, and half were
      killed after 10 days (day 10 group) for indirect assessment of adduct repair. In
      the day 1 group, acrolein-DNA adducts were 5 times higher in the 1 and 10 ppm
      groups than in HEPA-filtered air controls. However, in the day 10 group, adduct
      levels in the 1 and 10 ppm acrolein groups were reduced to the control adduct
      level. For the plaque studies, cockerels inhaled 1 ppm acrolein (6 hr/day, 8
      weeks), mixed with the same HEPA-filtered air inhaled by controls. Plaque
      development was measured blind by computerized morphometry. Unlike butadiene
      inhalation, acrolein inhalation did not accelerate plaque development. Thus, even
      though repeated exposure to acrolein alone has no effect on plaque size under the
      exposure conditions described here, a single, brief inhalation exposure to
      acrolein elicits repairable DNA damage to the artery wall. These results suggest
      that frequent exposure to ETS may lead to persistent artery-wall DNA damage and
      thus provide sites on which other ETS plaque accelerants can act.

PMID- 11333182
TI  - Involvement of the glycoproteic Ib-V-IX complex in nickel-induced platelet
      activation.
AB  - We studied the effect of nickel ions on platelet function because hypernickelemia
      has been found in patients with acute myocardial infarction. We previously
      demonstrated that nickel can activate an intracellular pathway leading to
      cytoskeleton reorganization consequent to tyrosine phosphorylation of p60(src) in
      human platelets independently of integrin alpha-IIb-beta(3). Moreover, in von
      Willebrand factor-stimulated platelets, the tyrosine phosphorylation of pp60(c
      src) is closely associated with the activation of phosphatidylinositol 3-kinase
      (PIK), and two adhesion receptors, glycoprotein (Gp)Ib and GpIIb/IIIa(alpha-IIb
      beta(3)), are involved. In our study, 1 and 5 mM nickel in the presence of
      fibrinogen induced platelet aggregation (independently of protein kinase C
      activation) and secretion. The pretreatment with a PIK inhibitor, wortmannin,
      strongly decreased nickel-induced platelet aggregation. Platelet treatment with
      mocarhagin, a cobra venom metalloproteinase that cleaves GpIba, significantly
      reduced aggregation induced by 5 mM without affecting the response to other
      agonists such as adenosine diphosphate (ADP). Moreover, nickel caused PIK
      translocation to the cytoskeleton. Taken together, these observations suggest a
      partial involvement of both integrins alpha-IIb-beta(3) and GpIb-V-IX complex in
      Ni(2+)-induced platelet activation.

PMID- 11333183
TI  - Abnormalities of sexual development in male rats with in utero and lactational
      exposure to the antiandrogenic plasticizer Di(2-ethylhexyl) phthalate.
AB  - Several members of the phthalate ester family have antiandrogenic properties, yet
      little is known about how exposure to these ubiquitous environmental contaminants
      early in development may affect sexual development. We conducted experiments to
      determine effects of in utero and lactational exposure to the most prevalent
      phthalate ester, di(2-ethylhexyl) phthalate (DEHP), on male reproductive system
      development and sexual behavior. Sprague-Dawley rats were dosed with corn oil or
      DEHP (0, 375, 750, or 1,500 mg/kg/day, per os) from gestation day 3 through
      postnatal day (PND) 21. Dose-related effects on male offspring included reduced
      anogenital distance, areola and nipple retention, undescended testes, and
      permanently incomplete preputial separation. Testis, epididymis, glans penis,
      ventral prostate, dorsolateral prostate, anterior prostate, and seminal vesicle
      weights were reduced at PND 21, 63, and/or 105-112. Additional dose-related
      effects included a high incidence of anterior prostate agenesis, a lower
      incidence of partial or complete ventral prostate agenesis, occasional
      dorsolateral prostate and seminal vesicle agenesis, reduced sperm counts, and
      testicular, epididymal, and penile malformations. Many DEHP-exposed males were
      sexually inactive in the presence of receptive control females, but sexual
      inactivity did not correlate with abnormal male reproductive organs. These
      results suggest that in utero and lactational DEHP exposure also inhibited
      sexually dimorphic central nervous system development. No major abnormalities
      were found in any of eight control litters, but DEHP caused severe male
      reproductive system toxicity in five of eight litters at 375 mg/kg/day, seven of
      eight litters at 750 mg/kg/day, and five of five litters at 1,500 mg/kg/day.
      These results demonstrate that the male reproductive system is far more sensitive
      to DEHP early in development than when animals are exposed as juveniles or
      adults. The effects of DEHP on male reproductive organs and sexual behaviors and
      the lack of significant effects on time to vaginal opening and first estrus in
      their littermates demonstrate that DEHP (and/or its metabolites) affects
      development of the male reproductive system primarily by acting as an
      antiandrogen. The pattern of effects of in utero and lactational DEHP exposure
      differed from patterns caused by other phthalate esters, and the preponderance of
      anterior prostate agenesis appears to be unique among all chemicals. These
      results suggest that DEHP acts partly by mechanisms distinct from those of other
      antiandrogens.

PMID- 11333184
TI  - In vitro and in vivo estrogenicity of UV screens.
AB  - Ultraviolet (UV) screens are increasingly used as a result of growing concern
      about UV radiation and skin cancer; they are also added to cosmetics and other
      products for light stability. Recent data on bioaccumulation in wildlife and
      humans point to a need for in-depth analyses of systemic toxicology, in
      particular with respect to reproduction and ontogeny. We examined six frequently
      used UVA and UVB screens for estrogenicity in vitro and in vivo. In MCF-7 breast
      cancer cells, five out of six chemicals, that is, benzophenone-3 (Bp-3),
      homosalate (HMS), 4-methyl-benzylidene camphor (4-MBC), octyl-methoxycinnamate
      (OMC), and octyl-dimethyl-PABA (OD-PABA), increased cell proliferation with
      median effective concentrations (EC(50)) values between 1.56 and 3.73 microM,
      whereas butyl-methoxydibenzoylmethane (B-MDM) was inactive. Further evidence for
      estrogenic activity was the induction of pS2 protein in MCF-7 cells and the
      blockade of the proliferative effect of 4-MBC by the estrogen antagonist ICI
      182,780. In the uterotrophic assay using immature Long-Evans rats that received
      the chemicals for 4 days in powdered feed, uterine weight was dose-dependently
      increased by 4-MBC (ED(50 )309mg/kg/day), OMC (ED(50) 935 mg/kg/day), and weakly
      by Bp-3 (active at 1,525 mg/kg/day). Three compounds were inactive by the oral
      route in the doses tested. Dermal application of 4-MBC to immature hairless
      (hr/hr) rats also increased uterine weight at concentrations of 5 and 7.5% in
      olive oil. Our findings indicate that UV screens should be tested for endocrine
      activity, in view of possible long-term effects in humans and wildlife.

PMID- 11333185
TI  - Arsenic alters the function of the glucocorticoid receptor as a transcription
      factor.
AB  - Chronic human exposure to nonovertly toxic doses of arsenic is associated with an
      increased risk of cancer. Although its carcinogenic mechanism is still unknown,
      arsenic does not directly cause DNA damage or mutations and is therefore thought
      to act principally as a co-mutagen, co-carcinogen, and/or tumor promoter.
      Previous studies in our laboratory demonstrated that effects of low-dose arsenic
      (III) (arsenite) on expression of the hormone-regulated phosphoenolpyruvate
      carboxykinase (PEPCK) gene were strongly associated with the glucocorticoid
      receptor (GR)-mediated regulatory pathway. We therefore examined specifically the
      effects of arsenite on the biochemical function of GR in hormone-responsive H4IIE
      rat hepatoma cells. Completely noncytotoxic arsenite treatments (0.3-3.3 microM)
      significantly decreased dexamethasone-induced expression of transiently
      transfected luciferase constructs containing either an intact hormone-responsive
      promoter from the mammalian PEPCK gene or two tandem glucocorticoid response
      elements (GRE). Western blotting and confocal microscopy of a green fluorescent
      protein-tagged-GR fusion protein demonstrated that arsenite pretreatment did not
      block the normal dexamethasone-induced nuclear translocation of GR. These data
      indicate that nontoxic doses of arsenite can interact directly with GR complexes
      and selectively inhibit GR-mediated transcription, which is associated with
      altered nuclear function rather than a decrease in hormone-induced GR activation
      or nuclear translocation.

PMID- 11333186
TI  - Exposure of rural and urban populations in KwaZulu Natal, South Africa, to
      fumonisin B(1) in maize.
AB  - We surveyed households in rural and urban areas of KwaZulu Natal, South Africa,
      to assess the exposure of the inhabitants to fumonisin B(1) (FB(1)), a mycotoxin
      produced by Fusarium verticillioides. In southern African regions maize, used as
      a staple food by the population, is prone to F. verticillioides infection.
      Furthermore, high levels of FB(1) in maize have been associated with esophageal
      cancer in South Africa. We assessed exposure of the population to FB(1) at three
      levels, namely, by analyzing stored maize, plate-ready food, and feces. The
      positions of participating households in the rural area were recorded using
      geographic information systems (GIS) for ease and accuracy of follow-up. Of the
      50 rural maize samples examined, 32% had levels of FB(1) ranging from 0.1-22.2
      mg/kg, whereas 29% of the 28 cooked maize (phutu) samples contained FB(1) ranging
      from 0.1-0.4 mg/kg. The incidence and levels of FB(1) in feces were 33% and 0.5
      39.0 mg/kg, respectively. Of the 49 urban maize samples analyzed 6.1% had a range
      of 0.2-0.5 mg/kg FB(1), whereas 3 of 44 fecal samples (6%) ranged between 0.6 and
      16.2 mg/kg. No FB(1) was detected in urban phutu samples. Because these levels
      are lower than those published from regions in South Africa with high incidence
      of esophageal cancer, it may be concluded that the risk of esophageal cancer from
      FB(1) exposure is lower in the KwaZulu Natal region.

PMID- 11333187
TI  - Sexual dimorphism of brain aromatase activity in medaka: induction of a female
      phenotype by estradiol.
AB  - In this study we identified sex-dependent dimorphism of brain aromatase in the
      teleost medaka and examined its regulation by sex steriods. We first investigated
      differential distribution of brain aromatase activity in sexually mature male and
      female medaka in serial coronal sections of the brain and identified the
      hypothalamic nuclei contained in each section using the brain atlas of medaka. In
      the brain of male medaka, high levels of activity are localized in sections
      containing the preoptic (POA) and suprachiasmatic nuclei (SC) (63-75 fmol/hr) and
      low levels in the nuclei periventricular dorsalis (HD), ventralis (HV), and
      caudalis (Hc), nuclei diffusus of lobulus inferiores (NDIL), and nuclei tuberi
      anteriores (TA) and posteriores (TP) (< 25 fmol/hr). In the brain of female
      medaka high aromatase activity is localized in sections containing the HD, HV,
      Hc, NDIL, TA, and TP (85-80 fmol/hr) and highly variable levels in the POA and SC
      (23-70 fmol/hr). The concentration and time dependency of the exposure of male
      medaka to estradiol on the total brain aromatase activity and morphologic sex
      characteristics were determined next. Estradiol increased the activity of brain
      aromatase in a concentration-dependent manner at 2.5 and 25 microg/L, but the
      increase was lower at higher concentrations of the hormone. The effect was time
      dependent, gradually increasing up to the fifth day of exposure, after which it
      reached a plateau. Estradiol induction of brain aromatase analyzed using
      Lineweaver-Burke plots of saturation assays revealed a non-first-order reaction.
      The results indicate that a positive feedback mechanism regulates brain aromatase
      and imply that the sexual dimorphic distribution of aromatase may be highly
      sensitive to physiologic cues and environmental perturbations in fish.

PMID- 11333188
TI  - The Belgian PCB and dioxin incident of January-June 1999: exposure data and
      potential impact on health.
AB  - In January 1999, 500 tons of feed contaminated with approximately 50 kg of
      polychlorinated biphenyls (PCBs) and 1 g of dioxins were distributed to animal
      farms in Belgium, and to a lesser extent in the Netherlands, France, and Germany.
      This study was based on 20,491 samples collected in the database of the Belgian
      federal ministries from animal feed, cattle, pork, poultry, eggs, milk, and
      various fat-containing food items analyzed for their PCB and/or dioxin content.
      Dioxin measurements showed a clear predominance of polychlorinated dibenzofuran
      over polychlorinated dibenzodioxin congeners, a dioxin/PCB ratio of approximately
      1:50,000 and a PCB fingerprint resembling that of an Aroclor mixture, thus
      confirming contamination by transformer oil rather than by other environmental
      sources. In this case the PCBs contribute significantly more to toxic equivalents
      (TEQ) than dioxins. The respective means +/- SDs and the maximum concentrations
      of dioxin (expressed in TEQ) and PCB observed per gram of fat in contaminated
      food were 170.3 +/- 487.7 pg, 2613.4 pg, 240.7 +/- 2036.9 ng, and 51059.0 ng in
      chicken; 1.9 +/- 0.8 pg, 4.3 pg, 34.2 +/- 30.5 ng, and 314.0 ng in milk; and 32.0
      +/- 104.4 pg, 713.3 pg, 392.7 +/- 2883.5 ng, and 46000.0 ng in eggs. Assuming
      that as a consequence of this incident between 10 and 15 kg PCBs and from 200 to
      300 mg dioxins were ingested by 10 million Belgians, the mean intake per kilogram
      of body weight is calculated to maximally 25,000 ng PCBs and 500 pg international
      TEQ dioxins. Estimates of the total number of cancers resulting from this
      incident range between 40 and 8,000. Neurotoxic and behavioral effects in
      neonates are also to be expected but cannot be quantified. Because food items
      differed widely (more than 50-fold) in the ratio of PCBs to dioxins, other
      significant sources of contamination and a high background contamination are
      likely to contribute substantially to the exposure of the Belgian population.

PMID- 11333189
TI  - Stimulation of contraction of pregnant rat uterus in vitro by non-dechlorinated
      and microbially dechlorinated mixtures of polychlorinated biphenyls.
AB  - A previous study of six polychlorinated biphenyl (PCB) congeners showed that PCBs
      with four or fewer chlorines and ortho substitution stimulate uterine contraction
      frequency in vitro, whereas congeners with a greater number of chlorines or non
      ortho substitution are inactive in vitro. We tested the hypothesis that PCB
      mixtures stimulate uterine contractions in a manner inversely related to the
      degree of chlorination and the presence of chlorines in the ortho- position of
      the biphenyl constituents of the mixtures. Uterine strips from pregnant rats were
      suspended in standard muscle baths and analyzed for changes in isometric
      contractions in response to in vitro exposure to commercial PCB mixtures
      (Aroclors) and their dechlorinated products after microbial degradation. The PCB
      mixtures Aroclor 1242, 1248, and 1254 significantly stimulated uterine
      contraction frequency, and the least chlorinated mixture, Aroclor 1242, was the
      most potent stimulant. Microbes from Hudson River sediment dechlorinated Aroclor
      1242 and Aroclor 1254 under reducing conditions to produce mixtures with an
      increased proportion of ortho-substituted congeners with one or two chlorine
      substitutions. The PCB mixtures that had undergone microbial reductive
      dechlorination stimulated uterine contraction frequency to a significantly
      greater extent than the parent mixtures. These results show that increased
      uterotonic activity was associated with decreased chlorination and increased
      ortho substitution of the biphenyl constituents of the mixtures.

PMID- 11333190
TI  - Contribution of lead from calcium supplements to blood lead.
AB  - We conducted a case-control study to determine the contribution of lead to blood
      from consumption of calcium supplements approximating the recommended daily
      intakes over a 6-month period. Subjects were males and females ages 21 to 47
      years (geometric mean 32 years) with a geometric mean blood lead concentration of
      2.5 microg/dL. They were subdivided into three groups. One treatment group (n =
      8) was administered a complex calcium supplement (carbonate/phosphate/citrate)
      and the other treatment group (n = 7) calcium carbonate. The control group (n =
      6) received no supplement. The lead isotopic compositions of the supplements were
      completely different from those of the blood of the subjects, allowing us easily
      to estimate contribution from the supplements. The daily lead dose from the
      supplements at 100% compliance was about 3 microg Pb. Three blood samples were
      taken at 2-month intervals before treatment to provide background values, and
      three were taken during treatment. Subjects in the treatment group were thus
      their own controls. Lead isotopic compositions for the complex supplement showed
      minimal change during treatment compared with pretreatment. Lead isotopic
      compositions in blood for the calcium carbonate supplement showed increases of up
      to 0.5% in the (206)Pb/(204)Pb ratio, and for all isotope ratios there was a
      statistically significant difference between baseline and treatment (p < 0.005).
      The change from baseline to treatment for the calcium carbonate supplement
      differed from that for both the control group and the group administered the
      complex supplement. Blood lead concentrations, however, showed minimal changes.
      Variations in blood lead levels over time did not differ significantly between
      groups. Our results are consistent with earlier investigations using radioactive
      and stable lead tracers, which showed minimal gastrointestinal absorption of lead
      in the presence of calcium (+/- phosphorus) in adults. Even though there is no
      discernible increase in blood lead concentration during treatment, there are
      significant changes in the isotopic composition of lead in blood arising from the
      calcium carbonate supplement, indicating a limited input of lead from diet into
      the blood. Because calcium carbonate is overwhelmingly the most popular calcium
      supplement, the changes we have observed merit further investigation. In
      addition, this type of study, combined with a duplicate diet, needs to be
      repeated for children, whose fractional absorption of lead is considerably higher
      than that of adults.

PMID- 11333191
TI  - Chlorophyll derived from Chlorella inhibits dioxin absorption from the
      gastrointestinal tract and accelerates dioxin excretion in rats.
AB  - We investigated the effects of chlorophyll derived from Chlorella on
      gastrointestinal absorption of seven types of polychlorinated dibenzo-p-dioxin
      (PCDD) and 10 types of polychlorinated dibenzofuran (PCDF) in Wistar rats. Twenty
      eight rats were randomly distributed into seven groups (n = 4). After overnight
      food deprivation, rats were given 4 g of the basal diet or 4 g of the chlorophyll
      diet containing 0.01-0.5% chlorophyll one time on day 1; each diet also contained
      0.2 mL PCDD and PCDF standard solutions. The amounts of fecal excretion of PCDD
      and PCDF congeners from days 1 to 5 in the group fed 0.01% chlorophyll were 64.8%
      for 1,2,3,7,8-pentaCDD, 78.6% for 1,2,3,4,7,8-hexaCDD, 73.5% for 1,2,3,6,7,8
      hexaCDD, 58.5% for 1,2,3,7,8,9-hexaCDD, 33.3% for 1,2,3,4,6,7,8-heptaCDD, 85.7%
      for 1,2,3,7,8-pentaCDF, 77.3% for 2,3,4,7,8-pentaCDF, 88.6% for 1,2,3,4,7,8
      hexaCDF, 78.0% for 1,2,3,6,7,8-hexaCDF, 62.5% for 1,2,3,7,8,9-hexaCDF, 84.1% for
      2,3,4,6,7,8-hexaCDF, 41.7% for 1,2,3,4,6,7,8-heptaCDF, and 40.0% for
      1,2,3,4,6,7,8-heptaCDF greater (p < 0.01) than those of the control group,
      respectively. The fecal excretion of PCDD and PCDF congeners was remarkably
      increased along with the increasing dietary chlorophyll. The amounts of PCDD and
      PCDF congeners in rats on day 5 administered dioxin mixtures were lower in the
      0.01% chlorophyll group than in the control group, ranging from 3.5 to 50.0% for
      PCDD congeners and from 3.7 to 41.7% lower for PCDF congeners, except for 2,3,7,8
      tetrachlorodibenzofuran. The amount of PCDD and PCDF congeners in rats was
      remarkably decreased along with the increasing dietary chlorophyll. These
      findings suggest that chlorophyll is effective for preventing dioxin absorption
      via foods.

PMID- 11333192
TI  - Occupational exposure to lead and induction of genetic damage.
AB  - To investigate whether occupational exposure to lead is genotoxic, we evaluated
      data from 103 lead-exposed workers and 78 matched controls. These data correspond
      to three different sampling periods, and we measured genetic damage as increases
      in the frequency of binucleated cells with micronuclei (BNMN) in peripheral blood
      lymphocytes. The levels of exposure were determined according to the lead levels
      in blood. Clearly significant increases in BNMN were observed in the exposed
      groups when compared to the control group. In addition, for the overall
      population (n = 181), we observed a clear relationship between lead levels in
      blood and BNMN (r = 0.497; p < 0.001). When we examined four exposure levels-
      very low exposure (< 1.20 microM/L), low exposure (1.20-1.91 microM/L), high
      exposure (1.92-2.88 microM/L), and very high exposure (> 2.88 microM/L)--we found
      significant differences in the genetic damage induction. We conclude that
      exposure to levels of lead higher than 1.20 microM/L may pose an increase in
      genetic risk. In addition, our data show that blood lead level is a good
      indicator of genetic damage induction.

PMID- 11333193
TI  - Biological monitoring survey of organophosphorus pesticide exposure among pre
      school children in the Seattle metropolitan area.
AB  - In this study we assessed organophosphorus (OP) pesticide exposure among children
      living in two Seattle metropolitan area communities by measuring urinary
      metabolites, and identified possible exposure risk factors through a parental
      interview. We recruited children in clinic and outpatient waiting rooms. We
      obtained spot urine samples in the spring and fall of 1998 from 110 children ages
      2-5 years, from 96 households. We analyzed urine samples for six dialkylphosphate
      (DAP) compounds, the common metabolites of the OP pesticides. Through parental
      interviews we gathered demographic and residential pesticide use data. At least
      one of the DAP metabolites was measured in 99% of the children, and the two
      predominant metabolites (DMTP and DETP) were measured in 70-75% of the children.
      We found no significant differences in DAP concentrations related to season,
      community, sex, age, family income, or housing type. Median concentrations of
      dimethyl and diethyl DAPs were 0.11 and 0.04 micromol/L, respectively (all
      children). Concentrations were significantly higher in children whose parents
      reported pesticide use in the garden (0.19 vs. 0.09 micromol/L for dimethyl
      metabolites, p = 0.05; 0.04 vs. 0.03 micromol/L for diethyl metabolites, p =
      0.02), but were not different based on reported pet treatment or indoor
      residential use. Nearly all children in this study had measurable levels of OP
      pesticide metabolites. Some of this exposure was likely due to diet. Garden
      pesticide use was associated with elevated metabolite levels. It is unlikely that
      these exposure levels would cause acute intoxication, but the long-term health
      effects of such exposures are unknown. We recommend that OP pesticide use be
      avoided in areas where children are likely to play.

PMID- 11333194
TI  - Lung cancer in a nonsmoking underground uranium miner.
AB  - Working in mines is associated with acute and chronic occupational disorders.
      Most of the uranium mining in the United States took place in the Four Corners
      region of the Southwest (Arizona, Colorado, New Mexico, and Utah) and on Native
      American lands. Although the uranium industry collapsed in the late 1980s, the
      industry employed several thousand individuals who continue to be at increased
      risk for developing lung cancers. We present the case of a 72-year-old Navajo
      male who worked for 17 years as an underground uranium miner and who developed
      lung cancer 22 years after leaving the industry. His total occupational exposure
      to radon progeny was estimated at 506 working level months. The miner was a life
      long nonsmoker and had no other significant occupational or environmental
      exposures. On the chest X-ray taken at admission into the hospital, a right lower
      lung zone infiltrate was detected. The patient was treated for community-acquired
      pneumonia and developed respiratory failure requiring mechanical ventilation.
      Respiratory failure worsened and the patient died 19 days after presenting. On
      autopsy, a 2.5 cm squamous cell carcinoma of the right lung arising from the
      lower lobe bronchus, a right broncho-esophageal fistula, and a right lower lung
      abscess were found. Malignant respiratory disease in uranium miners may be from
      several occupational exposures; for example, radon decay products, silica, and
      possibly diesel exhaust are respiratory carcinogens that were commonly
      encountered. In response to a growing number of affected uranium miners, the
      Radiation Exposure Compensation Act (RECA) was passed by the U.S. Congress in
      1990 to make partial restitution to individuals harmed by radiation exposure
      resulting from underground uranium mining and above-ground nuclear tests in
      Nevada.

PMID- 11333195
TI  - Errors in TCE analysis.
AB  - Comments on Wartenberg D, Reyner D, Scott CS's article "richloroethylene and
      cancer: epidemiologic evidence." Environ Health Perspect 108(suppl 2):161-176
      (2000)

PMID- 11333197
TI  - Toward resolution of the divergent effects of estrogens on the prostate gland of
      CF-1 mice.

PMID- 11333198
TI  - Prevalence of headache among handheld cellular telephone users.

PMID- 11333200
TI  - Tobacco in Africa.

PMID- 11333201
TI  - UN takes aim at small arms.

PMID- 11333202
TI  - Working around PD.

PMID- 11333203
TI  - Dioxin in Vietnam: fighting a legacy of war.
AB  - Singapore was the site of an East-West convergence over the week of 27 November-1
      December 2000. At the behest of their respective governments, scientists from the
      United States and Vietnam came together for what promises to be the first of many
      meetings. Their mission: to explore the possibility of launching a joint research
      program to study the human and environmental health effects resulting from
      spraying Agent Orange and other herbicides during the Vietnam War.

PMID- 11333204
TI  - Environmental Florence Nightingales: nursing's new front line.
AB  - Nurses comprise the largest health professional group in terms of number, and
      they can be found in almost every health care setting, including homes, schools,
      work sites, and hospitals. To a large extent, nurses have always been aware of
      environmental factors when doing their job, but the definition of environmental
      health nursing is being expanded. Today, in addition to considering the
      possibility of environmental influences when taking patient health histories,
      evaluating symptoms, and conducting community assessments, nurses may change
      environmental conditions of affected individuals or populations through direct
      care, teaching, advocacy, and public policy initiatives. Nurses are helping
      patients evaluate the relative risks of various types of environmental exposures,
      such as lead. And they are also playing a key role in establishing a national
      tracking system of environmental health as well as in conducting patient
      research.

PMID- 11333205
TI  - Green trees for greenhouse gases: a fair trade-off?
AB  - While forests retain carbon in plants, detritus, and soils, utility companies
      spew it into the air as carbon dioxide, the main greenhouse gas behind global
      warming. Industrial carbon dioxide emissions aren't currently regulated by
      federal law, but a number of companies are trying to address the problem
      voluntarily by launching carbon sequestration programs in heavily forested
      countries, where carbon is contained in so-called sinks. But the November 2000
      meeting of the Kyoto Protocol delegates in The Hague collapsed over the issue of
      the acceptability of carbon sinks as a source of carbon pollution credits,
      delivering what many see as a deathblow to the concept. At issue are a host of
      ecological and statistical questions, differing local land use practices,
      cultural factors, issues of verifiability, and even disagreement over definitions
      of basic terms such as "forest" Kyoto negotiators are gearing up for another
      round of discussions in Bonn in May 2001, and it is likely that the continuing
      debate over carbon sinks will dominate the agenda.

PMID- 11333206
TI  - Smelling in color: a rainbow of possibilities.
AB  - A sensor that detects dangerous odors better than the human nose may be able to
      "smell" dangerous air pollutants, soil contaminants, insecticides, food
      pathogens, biological warfare neurotoxins, and body odors associated with illness
      and disease. Called "smell-seeing" by its inventors, the method relies on color
      changes that occur in an array of vapor-sensitive dyes in response to exposure.
      By measuring the color change pattern, the researchers can identify a contaminant
      both qualitatively and quantitatively. This newest version of an artificial nose
      is simple, fast, and inexpensive. It can also eliminate the subjectivity
      associated with the human sense of smell and the perception of odors.

PMID- 11333207
TI  - Intercellular communication in preimplantation development: the role of gap
      junctions.
AB  - Gap junctions are sites where intercellular membrane channels are clustered that
      allow neighboring cells to pass small molecules directly between them. Gap
      junctional intercellular communication has been implicated in a variety of human
      diseases. Gap junction channels are assembled from a large family of proteins
      called connexins with each type of channel having some unique properties.
      Preimplantation mouse and rat embryos express multiple connexins and thus
      potentially contain many types of gap junction channels. Based on experiments
      focussing on connexin43, gap junction assembly in the mouse begins during
      compaction in the 8-cell stage and is post-translationally regulated. Gene
      targeting has been used to create mice lacking individual connexins that are
      expressed in preimplantation embryos, but none of these experiments has yet
      revealed a necessary role for any single connexin before implantation.
      Experiments with anti-connexin antibodies and pharmacological blockers of gap
      junctional coupling have provided conflicting evidence as to the importance of
      gap junctions for preimplantation development. However, connexin knockouts have
      revealed important roles for gap junctional coupling in early postimplantation
      development. It is proposed that expression of multiple connexins in the
      blastocyst could prepare the implanting conceptus for rapid diversification of
      cell types during gastrulation and development of the placenta.

PMID- 11333208
TI  - The role of EGF-related peptides in tumor growth.
AB  - The epidermal growth factor (EGF) family of peptides encodes several proteins
      that can function as growth factors. The EGF-like peptides, with the exception of
      proteins of the EGF-CFC subfamily, bind and activate tyrosine kinase receptors
      that belong to the erbB family. The EGF-like peptides are overexpressed in a
      majority of human carcinomas as compared with their nontransformed counterpart.
      By using different approaches, it has been shown that several different EGF-like
      peptides function as autocrine growth factors in carcinoma cell lines of
      different histological origin. Direct evidence that the EGF-like growth factors
      might function as transforming genes has been provided by in vitro and in vivo
      studies. In particular, the development of different transgenic mouse lines in
      which EGF-like growth factors have been overexpressed by means of tissue-specific
      or nonspecific promoters has provided invaluable information relating to their
      ability to function as dominantly transforming oncogenes. Cooperation of the EGF
      like peptides with cellular protooncogenes in determining cell transformation has
      been demonstrated by using both in vitro and transgenic mice systems. Taken
      together, these data strongly suggest that the EGF-like peptides are involved in
      the pathogenesis of human carcinomas, and that they might represent suitable
      targets for novel therapeutic approaches.

PMID- 11333209
TI  - Determinants and mechanisms of attentional modulation of neural processing.
AB  - This review contrasts the most-studied variety of attention, visuospatial
      attention, with several types of nonspatial visual attention. We: 1) discuss the
      manner in which spatial and nonspatial varieties of attention are experimentally
      defined, and the ecological validity of the paradigms in which they are studied,
      2) review and compare differing effects of spatial and nonspatial attention on
      neural processing, 3) discuss the manner in which attention operates within the
      framework of an anatomical visual hierarchy, as well as 4) how attention relates
      to the temporal dynamics of visual processing, 5) describe cellular circuits and
      physiological processes that appear to be involved in attention effects, 6)
      discuss the relationship of attentional physiology to the perceptual and
      cognitive effects of attention, and 7) consider the strengths and limitations of
      several current models of selective attention. Throughout, we attempt to
      integrate the findings of monkey and human studies whenever possible. We have
      three main conclusions. First, two models, the Neural Specificity Model of Harter
      and colleagues and the Feature Similarity Gain Model of Treue and colleagues best
      incorporate findings in relation to both spatial and nonspatial varieties of
      attention. Significantly, these models explicitly note that the specific neuronal
      components used in attentional modulation of processing are flexible and
      determined by task demands. Second, current evidence also provides strong bases
      for deriving testable hypotheses about the specific brain mechanisms utilized by
      attention. Cellular processes, brain circuits and neurotransmitter components can
      and should be incorporated into our models of attention. Finally, it is
      increasingly evident that we can and should analyze temporal patterns of
      attentional modulation, both within and across brain areas. These patterns
      provide critical information on the dynamics of attention.

PMID- 11333210
TI  - Regulation of blastocyst formation.
AB  - Preimplantation or pre-attachment development encompasses the "free"-living
      period of mammalian embryogenesis, which directs development of the zygote
      through to the blastocyst stage. Blastocyst formation is essential for
      implantation, establishment of pregnancy and is a principal determinant of embryo
      quality prior to embryo transfer. Cavitation (blastocyst formation) is driven by
      the expression of specific sets of gene products that direct the acquisition of
      cell polarity within the trophectoderm, which is both the first epithelium of
      development and the outer cell layer encircling the inner cell mass of the
      blastocyst. Critical gene families controlling these events include: the E
      cadherin-catenin cell adhesion family, the tight junction gene family, the Na/K
      ATPase gene family and perhaps the aquaporin gene family. This review will update
      the roles of each of these gene families in trophectoderm differentiation and
      blastocyst formation. The current principal hypothesis under investigation is
      that blastocyst formation is mediated by a trans-trophectoderm ion gradient(s)
      established, in part, by Na/K-ATPase, which drives the movement of water through
      aquaporins (AQPs) across the epithelium into the extracellular space of the
      blastocyst to form the fluid-filled blastocoel. The trophectoderm tight
      junctional permeability seal regulates the leakage of blastocoel fluid, and also
      assists in the maintenance of a polarized Na/K-ATPase distribution to the
      basolateral plasma membrane domain of the mural trophectoderm. The cell-to-cell
      adhesion provided by the E-cadherin-catenin gene families is required for the
      establishment of the tight junction seal and the maintenance of the polarized
      Na/K-ATPase distribution. Blastocyst formation is therefore directly linked with
      trophectoderm cell differentiation, which arises through fundamental cell
      biological processes that are associated with the establishment of cell polarity.

PMID- 11333212
TI  - Epidemic hemolytic-uremic syndrome related to bleomycin.

PMID- 11333213
TI  - My road to Ojvind Winge, the father of yeast genetics.

PMID- 11333214
TI  - Recognition and specific degradation of bacteriophage T4 mRNAs.
AB  - Gene 61.5 of bacteriophage T4 has a unique role in gene expression. When this
      gene is mutated, mRNAs of many late genes are rapidly degraded, resulting in late
      gene silencing. Here, we characterize an extragenic suppressor, ssf5, of a gene
      61.5 mutation. ssf5 was found to be an amber mutation in motA, which encodes a
      transcription activator for T4 middle genes. When this gene is mutated, both
      degradation and specific cleavage of late-gene mRNA is induced after a delay, as
      exemplified by soc mRNA. Consequently, partial late-gene expression occurs. In an
      ssf5 genetic background, a gene 61.5 mutation exhibits a novel phenotype: in
      contrast to late-gene mRNA, middle-gene mRNA is stabilized and the expression of
      middle genes is prolonged. This is attributable to an activity of gene 61.5
      specific for degradation of middle-gene mRNA. The degradation of middle-gene mRNA
      in the presence of a normal gene 61.5 appears in parallel with the degradation of
      late-gene mRNA in its absence. This observation suggests that the mRNA-degrading
      activity that silences late genes in cells infected with a gene 61.5 mutant is
      targeted to middle-gene mRNA when gene 61.5 is wild type. These results and the
      results obtained in the presence of a normal motA gene suggest that gene 61.5
      protein functions to discriminate mRNAs for degradation in a stage-dependent
      manner.

PMID- 11333215
TI  - Repair of topoisomerase-mediated DNA damage in bacteriophage T4.
AB  - Type II topoisomerase inhibitors are used to treat both tumors and bacterial
      infections. These inhibitors stabilize covalent DNA-topoisomerase cleavage
      complexes that ultimately cause lethal DNA damage. A functional recombinational
      repair apparatus decreases sensitivity to these drugs, suggesting that
      topoisomerase-mediated DNA damage is amenable to such repair. Using a
      bacteriophage T4 model system, we have developed a novel in vivo plasmid-based
      assay that allows physical analysis of the repair products from one particular
      topoisomerase cleavage site. We show that the antitumor agent 4'-(9
      acridinylamino)methanesulphon-m-anisidide (m-AMSA) stabilizes the T4 type II
      topoisomerase at the strong topoisomerase cleavage site on the plasmid, thereby
      stimulating recombinational repair. The resulting m-AMSA-dependent repair
      products do not form in the absence of functional topoisomerase and appear at
      lower drug concentrations with a drug-hypersensitive topoisomerase mutant. The
      appearance of repair products requires that the plasmid contain a T4 origin of
      replication. Finally, genetic analyses demonstrate that repair product formation
      is absolutely dependent on genes 32 and 46, largely dependent on genes uvsX and
      uvsY, and only partly dependent on gene 49. Very similar genetic requirements are
      observed for repair of endonuclease-generated double-strand breaks, suggesting
      mechanistic similarity between the two repair pathways.

PMID- 11333216
TI  - Role of DNA ligase in the illegitimate recombination that generates lambdabio
      transducing phages in Escherichia coli.
AB  - We studied the role of DNA ligase in illegitimate recombination in Escherichia
      coli. A temperature-sensitive mutation in the lig gene reduced the frequency with
      which lambdabio-transducing phages were generated to 10-14% of that of wild type
      under UV irradiation. Reintroduction of the lig gene into this mutant restored
      the frequency of recombinant phage generation to that of wild type. Furthermore,
      overexpression of DNA ligase enhanced illegitimate recombination by 10-fold with
      or without UV irradiation. In addition, when DNA ligase was present in only
      limited amounts, UV-induced or spontaneous illegitimate recombination occurred
      exclusively at hotspot sites that have relatively long sequences of homology (9
      or 13 bp). However, when DNA ligase was overexpressed, most of the illegitimate
      recombination took place at non-hotspot sites having only short sequences of
      homology (<4 bp). Thus, the level of ligase activity affects the frequency of
      illegitimate recombination, the length of sequence homology at the recombination
      sites, and the preference for recombination at hotspots, at least after UV
      irradiation. These observations support our hypothesis that the illegitimate
      recombination that generates lambdabio-transducing phages is mediated by the DNA
      break-and-join mechanism.

PMID- 11333217
TI  - Comparative gene expression profiles following UV exposure in wild-type and SOS
      deficient Escherichia coli.
AB  - The SOS response in UV-irradiated Escherichia coli includes the upregulation of
      several dozen genes that are negatively regulated by the LexA repressor. Using
      DNA microarrays containing amplified DNA fragments from 95.5% of all open reading
      frames identified on the E. coli chromosome, we have examined the changes in gene
      expression following UV exposure in both wild-type cells and lexA1 mutants, which
      are unable to induce genes under LexA control. We report here the time courses of
      expression of the genes surrounding the 26 documented lexA-regulated regions on
      the E. coli chromosome. We observed 17 additional sites that responded in a lexA
      dependent manner and a large number of genes that were upregulated in a lexA
      independent manner although upregulation in this manner was generally not more
      than twofold. In addition, several transcripts were either downregulated or
      degraded following UV irradiation. These newly identified UV-responsive genes are
      discussed with respect to their possible roles in cellular recovery following
      exposure to UV irradiation.

PMID- 11333218
TI  - Requirement for Msh6, but not for Swi4 (Msh3), in Msh2-dependent repair of base
      base mismatches and mononucleotide loops in Schizosaccharomyces pombe.
AB  - The msh6 mismatch repair gene of Schizosaccharomyces pombe was cloned, sequenced,
      and inactivated. Strains bearing all combinations of inactivated msh6, msh2, and
      swi4 (the S. pombe MSH3 ortholog) alleles were tested for their defects in
      mitotic and meiotic mismatch repair. Mitotic mutation rates were similarly
      increased in msh6 and msh2 mutants, both for reversion of a base-base
      substitution as well as of an insertion of one nucleotide in a mononucleotide
      run. Tetrad analysis and intragenic two-factor crosses revealed that meiotic
      mismatch repair was affected in msh6 to the same extent as in msh2 background. In
      contrast, loss of Swi4 likely did not cause a defect in mismatch repair, but
      rather resulted in reduced recombination frequency. Consistently, a mutated swi4
      caused a two- to threefold reduction of recombinants in intergenic crosses, while
      msh2 and msh6 mutants were not significantly different from wild type. In
      summary, our study showed that Msh6 plays the same important role as Msh2 in the
      major mismatch repair pathway of S. pombe, while Swi4 rather functions in
      recombination.

PMID- 11333219
TI  - Control of GT repeat stability in Schizosaccharomyces pombe by mismatch repair
      factors.
AB  - The mismatch repair (MMR) system ensures genome integrity by removing mispaired
      and unpaired bases that originate during replication. A major source of
      mutational changes is strand slippage in repetitive DNA sequences without
      concomitant repair. We established a genetic assay that allows measuring the
      stability of GT repeats in the ade6 gene of Schizosaccharomyces pombe. In repair
      proficient strains most of the repeat variations were insertions, with addition
      of two nucleotides being the most frequent event. GT repeats were highly
      destabilized in strains defective in msh2 or pms1. In these backgrounds, mainly 2
      bp insertions and 2-bp deletions occurred. Surprisingly, essentially the same
      high mutation rate was found with mutants defective in msh6. In contrast, a
      defect in swi4 (a homologue of Msh3) caused only slight effects, and instability
      was not further increased in msh6 swi4 double mutants. Also inactivation of exo1,
      which encodes an exonuclease that has an MMR-dependent function in repair of base
      base mismatches, caused only slightly increased repeat instability. We conclude
      that Msh2, Msh6, and Pms1 have an important role in preventing tract length
      variations in dinucleotide repeats. Exo1 and Swi4 have a minor function, which is
      at least partially independent of MMR.

PMID- 11333220
TI  - Multiple functions of the nonconserved N-terminal domain of yeast TATA-binding
      protein.
AB  - The TATA-binding protein (TBP) is composed of a highly conserved core domain
      sufficient for TATA-element binding and preinitiation complex formation as well
      as a highly divergent N-terminal region that is dispensable for yeast cell
      viability. In vitro, removal of the N-terminal region domain enhances TBP-TATA
      association and TBP dimerization. Here, we examine the effects of truncation of
      the N-terminal region in the context of yeast TBP mutants with specific defects
      in DNA binding and in interactions with various proteins. For a subset of
      mutations that disrupt DNA binding and the response to transcriptional
      activators, removal of the N-terminal domain rescues their transcriptional
      defects. By contrast, deletion of the N-terminal region is lethal in combination
      with mutations on a limited surface of TBP. Although this surface is important
      for interactions with TFIIA and Brf1, TBP interactions with these two factors do
      not appear to be responsible for this dependence on the N-terminal region. Our
      results suggest that the N-terminal region of TBP has at least two distinct
      functions in vivo. It inhibits the interaction of TBP with TATA elements, and it
      acts positively in combination with a specific region of the TBP core domain that
      presumably interacts with another protein(s).

PMID- 11333221
TI  - Saccharomyces cerevisiae SMT4 encodes an evolutionarily conserved protease with a
      role in chromosome condensation regulation.
AB  - In a search for regulatory genes affecting the targeting of the condensin complex
      to chromatin in Saccharomyces cerevisiae, we identified a member of the
      adenovirus protease family, SMT4. SMT4 overexpression suppresses the temperature
      sensitive conditional lethal phenotype of smc2-6, but not smc2-8 or smc4-1. A
      disruption allele of SMT4 has a prominent chromosome phenotype: impaired
      targeting of Smc4p-GFP to rDNA chromatin. Site-specific mutagenesis of the
      predicted protease active site cysteine and histidine residues of Smt4p abolishes
      the SMT4 function in vivo. The previously uncharacterized SIZ1 (SAP and Miz)
      gene, which encodes a protein containing a predicted DNA-binding SAP module and a
      Miz finger, is identified as a bypass suppressor of the growth defect associated
      with the SMT4 disruption. The SIZ1 gene disruption is synthetically lethal with
      the SIZ2 deletion. We propose that SMT4, SIZ1, and SIZ2 are involved in a novel
      pathway of chromosome maintenance.

PMID- 11333222
TI  - Fidelity of mitotic double-strand-break repair in Saccharomyces cerevisiae: a
      role for SAE2/COM1.
AB  - Errors associated with the repair of DNA double-strand breaks (DSBs) include
      point mutations caused by misincorporation during repair DNA synthesis or novel
      junctions made by nonhomologous end joining (NHEJ). We previously demonstrated
      that DNA synthesis is approximately 100-fold more error prone when associated
      with DSB repair. Here we describe a genetic screen for mutants that affect the
      fidelity of DSB repair. The substrate consists of inverted repeats of the trp1
      and CAN1 genes. Recombinational repair of a site-specific DSB within the repeat
      yields TRP1 recombinants. Errors in the repair process can be detected by the
      production of canavanine-resistant (can1) mutants among the TRP1 recombinants. In
      wild-type cells the recombinational repair process is efficient and fairly
      accurate. Errors resulting in can1 mutations occur in <1% of the TRP1
      recombinants and most appear to be point mutations. We isolated several mutant
      strains with altered fidelity of recombination. Here we characterize one of these
      mutants that revealed an approximately 10-fold elevation in the frequency of can1
      mutants among TRP1 recombinants. The gene was cloned by complementation of a
      coincident sporulation defect and proved to be an allele of SAE2/COM1. Physical
      analysis of the can1 mutants from sae2/com1 strains revealed that many were a
      novel class of chromosome rearrangement that could reflect break-induced
      replication (BIR) and NHEJ. Strains with either the mre11s-H125N or rad50s-K81I
      alleles had phenotypes in this assay that are similar to that of the
      sae2/com1Delta strain. Our data suggest that Sae2p/Com1p plays a role in ensuring
      that both ends of a DSB participate in a recombination event, thus avoiding BIR,
      possibly by regulating the nuclease activity of the Mre11p/Rad50p/Xrs2p complex.

PMID- 11333223
TI  - Minimum requirements for the function of eukaryotic translation initiation factor
      2.
AB  - Eukaryotic translation initiation factor 2 (eIF2) is a G protein heterotrimer
      required for GTP-dependent delivery of initiator tRNA to the ribosome. eIF2B, the
      nucleotide exchange factor for eIF2, is a heteropentamer that, in yeast, is
      encoded by four essential genes and one nonessential gene. We found that
      increased levels of wild-type eIF2, in the presence of sufficient levels of
      initiator tRNA, overcome the requirement for eIF2B in vivo. Consistent with
      bypassing eIF2B, these conditions also suppress the lethal effect of
      overexpressing the mammalian tumor suppressor PKR, an eIF2alpha kinase. The
      effects described are further enhanced in the presence of a mutation in the G
      protein (gamma) subunit of eIF2, gcd11-K250R, which mimics the function of eIF2B
      in vitro. Interestingly, the same conditions that bypass eIF2B also overcome the
      requirement for the normally essential eIF2alpha structural gene (SUI2). Our
      results suggest that the eIF2betagamma complex is capable of carrying out the
      essential function(s) of eIF2 in the absence of eIF2alpha and eIF2B and are
      consistent with the idea that the latter function primarily to regulate the level
      of eIF2.GTP.Met-tRNA(i)(Met) ternary complexes in vivo.

PMID- 11333224
TI  - Rap1p requires Gcr1p and Gcr2p homodimers to activate ribosomal protein and
      glycolytic genes, respectively.
AB  - Efficient transcription of ribosomal protein (RP) and glycolytic genes requires
      the Rap1p/Gcr1p regulatory complex. A third factor, Gcr2p, is required for only
      the glycolytic (specialized) mode of transcriptional activation. It is recruited
      to the complex by Gcr1p and likely mediates a change in the phosphorylation state
      and/or conformation of the latter. We show here that leucine zipper motifs in
      Gcr1p and Gcr2p (1LZ and 2LZ) are each specific to one of the two activation
      mechanisms-mutations in 1LZ and 2LZ impair transcription of RP and glycolytic
      genes, respectively. Although neither class of mutations causes more than a mild
      growth defect, simultaneous impairment of 1LZ and 2LZ results in a severe
      synthetic defect and a reduction in the expression of both sets of genes.
      Intracistronic complementation by point mutations in the charged e and g
      positions confirmed that Gcr1p/Gcr1p and Gcr2p/Gcr2p homodimers are the forms
      required for the different roles of the activator complex. Direct
      heterodimerization between 1LZ and 2LZ apparently does not occur. Dichotomous
      Rap1p activation and its striking requirement for distinct homodimeric subunits
      give cells the capacity to switch between coordinated and uncoupled RP and
      glycolytic gene regulation.

PMID- 11333225
TI  - The Saccharomyces cerevisiae suppressor of choline sensitivity (SCS2) gene is a
      multicopy Suppressor of mec1 telomeric silencing defects.
AB  - Mec1p is a cell cycle checkpoint protein related to the ATM protein kinase
      family. Certain mec1 mutations or overexpression of Mec1p lead to shortened
      telomeres and loss of telomeric silencing. We conducted a multicopy suppressor
      screen for genes that suppress the loss of silencing in strains overexpressing
      Mec1p. We identified SCS2 (suppressor of choline sensitivity), a gene previously
      isolated as a suppressor of defects in inositol synthesis. Deletion of SCS2
      resulted in decreased telomeric silencing, and the scs2 mutation increased the
      rate of cellular senescence observed for mec1-21 tel1 double mutant cells.
      Genetic analysis revealed that Scs2p probably acts through a different telomeric
      silencing pathway from that affected by Mec1p.

PMID- 11333226
TI  - Expansions and contractions in 36-bp minisatellites by gene conversion in yeast.
AB  - The instability of simple tandem repeats, such as human minisatellite loci, has
      been suggested to arise by gene conversions. In Saccharomyces cerevisiae, a
      double-strand break (DSB) was created by the HO endonuclease so that DNA
      polymerases associated with gap repair must traverse an artificial minisatellite
      of perfect 36-bp repeats or a yeast Y' minisatellite containing diverged 36-bp
      repeats. Gene conversions are frequently accompanied by changes in repeat number
      when the template contains perfect repeats. When the ends of the DSB have
      nonhomologous tails of 47 and 70 nucleotides that must be removed before repair
      DNA synthesis can begin, 16% of gene conversions had rearrangements, most of
      which were contractions, almost always in the recipient locus. When efficient
      removal of nonhomologous tails was prevented in rad1 and msh2 strains, repair was
      reduced 10-fold, but among survivors there was a 10-fold reduction in
      contractions. Half the remaining events were expansions. A similar decrease in
      the contraction rate was observed when the template was modified so that DSB ends
      were homologous to the template; and here, too, half of the remaining
      rearrangements were expansions. In this case, efficient repair does not require
      RAD1 and MSH2, consistent with our previous observations. In addition, without
      nonhomologous DSB ends, msh2 and rad1 mutations did not affect the frequency or
      the distribution of rearrangements. We conclude that the presence of
      nonhomologous ends alters the mechanism of DSB repair, likely through early
      recruitment of repair proteins including Msh2p and Rad1p, resulting in more
      frequent contractions of repeated sequences.

PMID- 11333227
TI  - Protosilencers in Saccharomyces cerevisiae subtelomeric regions.
AB  - Saccharomyces cerevisiae subtelomeric repeats contain silencing elements such as
      the core X sequence, which is present at all chromosome ends. When transplaced at
      HML, core X can enhance the action of a distant silencer without acting as a
      silencer on its own, thus fulfilling the functional definition of a
      protosilencer. Here we show that an ACS motif and an Abf1p-binding site
      participate in the silencing capacity of core X and that their effects are
      additive. In addition, in a variety of settings, core X was found to bring about
      substantial gene repression only when a low level of silencing was already
      detectable in its absence. Adjoining an X-STAR sequence, which naturally abuts
      core X in subtelomeric regions, did not improve the silencing capacity of core X.
      We propose that protosilencers play a major role in a variety of silencing
      phenomena, as is the case for core X, which acts as a silencing relay, prolonging
      silencing propagation away from telomeres.

PMID- 11333228
TI  - Identification of a mutant DNA polymerase delta in Saccharomyces cerevisiae with
      an antimutator phenotype for frameshift mutations.
AB  - We propose that a beta-turn-beta structure, which plays a critical role in
      exonucleolytic proofreading in the bacteriophage T4 DNA polymerase, is also
      present in the Saccharomyces cerevisiae DNA pol delta. Site-directed mutagenesis
      was used to test this proposal by introducing a mutation into the yeast POL3 gene
      in the region that encodes the putative beta-turn-beta structure. The mutant DNA
      pol delta has a serine substitution in place of glycine at position 447. DNA
      replication fidelity of the G447S-DNA pol delta was determined in vivo by using
      reversion and forward assays. An antimutator phenotype for frameshift mutations
      in short homopolymeric tracts was observed for the G447S-DNA pol delta in the
      absence of postreplication mismatch repair, which was produced by inactivation of
      the MSH2 gene. Because the G447S substitution reduced frameshift but not base
      substitution mutagenesis, some aspect of DNA polymerase proofreading appears to
      contribute to production of frameshifts. Possible roles of DNA polymerase
      proofreading in frameshift mutagenesis are discussed.

PMID- 11333229
TI  - Multiple functional interactions between components of the Lsm2-Lsm8 complex, U6
      snRNA, and the yeast La protein.
AB  - The U6 small nuclear ribonucleoprotein is a critical component of the eukaryotic
      spliceosome. The first protein that binds the U6 snRNA is the La protein, an
      abundant phosphoprotein that binds the 3' end of many nascent small RNAs. A
      complex of seven Sm-like proteins, Lsm2-Lsm8, also binds the 3' end of U6 snRNA.
      A mutation within the Sm motif of Lsm8p causes Saccharomyces cerevisiae cells to
      require the La protein Lhp1p to stabilize nascent U6 snRNA. Here we describe
      functional interactions between Lhp1p, the Lsm proteins, and U6 snRNA. LSM2 and
      LSM4, but not other LSM genes, act as allele-specific, low-copy suppressors of
      mutations in Lsm8p. Overexpression of LSM2 in the lsm8 mutant strain increases
      the levels of both Lsm8p and U6 snRNPs. In the presence of extra U6 snRNA genes,
      LSM8 becomes dispensable for growth, suggesting that the only essential function
      of LSM8 is in U6 RNA biogenesis or function. Furthermore, deletions of LSM5,
      LSM6, or LSM7 cause LHP1 to become required for growth. Our experiments are
      consistent with a model in which Lsm2p and Lsm4p contact Lsm8p in the Lsm2-Lsm8
      ring and suggest that Lhp1p acts redundantly with the entire Lsm2-Lsm8 complex to
      stabilize nascent U6 snRNA.

PMID- 11333230
TI  - Genes regulating touch cell development in Caenorhabditis elegans.
AB  - To identify genes regulating the development of the six touch receptor neurons,
      we screened the F(2) progeny of mutated animals expressing an integrated mec
      2::gfp transgene that is expressed mainly in these touch cells. From 2638 mutated
      haploid genomes, we obtained 11 mutations representing 11 genes that affected the
      production, migration, or outgrowth of the touch cells. Eight of these mutations
      were in known genes, and 2 defined new genes (mig-21 and vab-15). The mig-21
      mutation is the first known to affect the asymmetry of the migrations of Q
      neuroblasts, the cells that give rise to two of the six touch cells. vab-15 is a
      msh-like homeobox gene that appears to be needed for the proper production of
      touch cell precursors, since vab-15 animals lacked the four more posterior touch
      cells. The remaining touch cells (the ALM cells) were present but mispositioned.
      A similar touch cell phenotype is produced by mutations in lin-32. A more severe
      phenotype; i.e., animals often lacked ALM cells, was seen in lin-32 vab-15 double
      mutants, suggesting that these genes acted redundantly in ALM differentiation. In
      addition to the touch cell abnormalities, vab-15 animals variably exhibit
      embryonic or larval lethality, cell degenerations, malformation of the posterior
      body, uncoordinated movement, and defective egg laying.

PMID- 11333231
TI  - Rules of nonallelic noncomplementation at the synapse in Caenorhabditis elegans.
AB  - Nonallelic noncomplementation occurs when recessive mutations in two different
      loci fail to complement one another, in other words, the double heterozygote
      exhibits a phenotype. We observed that mutations in the genes encoding the
      physically interacting synaptic proteins UNC-13 and syntaxin/UNC-64 failed to
      complement one another in the nematode Caenorhabditis elegans. Noncomplementation
      was not observed between null alleles of these genes and thus this genetic
      interaction does not occur with a simple decrease in dosage at the two loci.
      However, noncomplementation was observed if at least one gene encoded a partially
      functional gene product. Thus, this genetic interaction requires a poisonous gene
      product to sensitize the genetic background. Nonallelic noncomplementation was
      not limited to interacting proteins: Although the strongest effects were observed
      between loci encoding gene products that bind to one another, interactions were
      also observed between proteins that do not directly interact but are members of
      the same complex. We also observed noncomplementation between genes that function
      at distant points in the same pathway, implying that physical interactions are
      not required for nonallelic noncomplementation. Finally, we observed that
      mutations in genes that function in different processes such as neurotransmitter
      synthesis or synaptic development complement one another. Thus, this genetic
      interaction is specific for genes acting in the same pathway, that is, for genes
      acting in synaptic vesicle trafficking.

PMID- 11333232
TI  - The G-protein beta-subunit GPB-2 in Caenorhabditis elegans regulates the
      G(o)alpha-G(q)alpha signaling network through interactions with the regulator of
      G-protein signaling proteins EGL-10 and EAT-16.
AB  - The genome of Caenorhabditis elegans harbors two genes for G-protein beta
      subunits. Here, we describe the characterization of the second G-protein beta
      subunit gene gpb-2. In contrast to gpb-1, gpb-2 is not an essential gene even
      though, like gpb-1, gpb-2 is expressed during development, in the nervous system,
      and in muscle cells. A loss-of-function mutation in gpb-2 produces a variety of
      behavioral defects, including delayed egg laying and reduced pharyngeal pumping.
      Genetic analysis shows that GPB-2 interacts with the GOA-1 (homologue of
      mammalian G(o)alpha) and EGL-30 (homologue of mammalian G(q)alpha) signaling
      pathways. GPB-2 is most similar to the divergent mammalian Gbeta5 subunit, which
      has been shown to mediate a specific interaction with a Ggamma-subunit-like (GGL)
      domain of RGS proteins. We show here that GPB-2 physically and genetically
      interacts with the GGL-containing RGS proteins EGL-10 and EAT-16. Taken together,
      our results suggest that GPB-2 works in concert with the RGS proteins EGL-10 and
      EAT-16 to regulate GOA-1 (G(o)alpha) and EGL-30 (G(q)alpha) signaling.

PMID- 11333233
TI  - Many genomic regions are required for normal embryonic programmed cell death in
      Caenorhabditis elegans.
AB  - To identify genes involved in programmed cell death (PCD) in Caenorhabditis
      elegans, we screened a comprehensive set of chromosomal deficiencies for
      alterations in the pattern of PCD throughout embryonic development. From a set of
      58 deficiencies, which collectively remove approximately 74% of the genome, four
      distinct classes were identified. In class I (20 deficiencies), no significant
      deviation from wild type in the temporal pattern of cell corpses was observed,
      indicating that much of the genome does not contain zygotic genes that perform
      conspicuous roles in embryonic PCD. The class II deficiencies (16 deficiencies
      defining at least 11 distinct genomic regions) led to no or fewer-than-normal
      cell corpses. Some of these cause premature cell division arrest, probably
      explaining the diminution in cell corpse number; however, others have little
      effect on cell proliferation, indicating that the reduced cell corpse number is
      not a direct result of premature embryonic arrest. In class III (18 deficiencies
      defining at least 16 unique regions), an excess of cell corpses was observed. The
      developmental stage at which the extra corpses were observed varied among the
      class III deficiencies, suggesting the existence of genes that perform temporal
      specific functions in PCD. The four deficiencies in class IV (defining at least
      three unique regions), showed unusually large corpses that were, in some cases,
      attributable to extremely premature arrest in cell division without a concomitant
      block in PCD. Deficiencies in this last class suggest that the cell death program
      does not require normal embryonic cell proliferation to be activated and suggest
      that while some genes required for cell division might also be required for cell
      death, others are not. Most of the regions identified by these deficiencies do
      not contain previously identified zygotic cell death genes. There are, therefore,
      a substantial number of as yet unidentified genes required for normal PCD in C.
      elegans.

PMID- 11333234
TI  - Embryonic expression of the divergent Drosophila beta3-tubulin isoform is
      required for larval behavior.
AB  - We have sought to define the developmental and cellular roles played by
      differential expression of distinct beta-tubulins. Drosophila beta3-tubulin
      (beta3) is a structurally divergent isoform transiently expressed during
      midembryogenesis. Severe beta3 mutations cause larval lethality resulting from
      failed gut function and consequent starvation. However, mutant larvae also
      display behavioral abnormalities consistent with defective sensory perception. We
      identified embryonic beta3 expression in several previously undefined sites,
      including different types of sensory organs. We conclude that abnormalities in
      foraging behavior and photoresponsiveness exhibited by prelethal mutant larvae
      reflect defective beta3 function in the embryo during development of chordotonal
      and other mechanosensory organs and of Bolwig's organ and nerve. We show that
      microtubule organization in the cap cells of chordotonal organs is altered in
      mutant larvae. Thus transient zygotic beta3 expression has permanent consequences
      for the architecture of the cap cell microtubule cytoskeleton in the larval
      sensilla, even when beta3 is no longer present. Our data provide a link between
      the microtubule cytoskeleton in embryogenesis and the behavioral phenotype
      manifested as defective proprioreception at the larval stage.

PMID- 11333235
TI  - Partitioning of N-ethylmaleimide-sensitive fusion (NSF) protein function in
      Drosophila melanogaster: dNSF1 is required in the nervous system, and dNSF2 is
      required in mesoderm.
AB  - The N-ethylmaleimide-sensitive fusion protein (NSF) promotes the fusion of
      secretory vesicles with target membranes in both regulated and constitutive
      secretion. While it is thought that a single NSF may perform this function in
      many eukaryotes, previous work has shown that the Drosophila genome contains two
      distinct NSF genes, dNSF1 and dNSF2, raising the possibility that each plays a
      specific secretory role. To explore this possibility, we generated mutations in
      the dNSF2 gene and used these and novel dNSF1 loss-of-function mutations to
      analyze the temporal and spatial requirements and the degree of functional
      redundancy between dNSF1 and dNSF2. Results of this analysis indicate that dNSF1
      function is required in the nervous system beginning at the adult stage of
      development and that dNSF2 function is required in mesoderm beginning at the
      first instar larval stage of development. Additional evidence suggests that dNSF1
      and dNSF2 may play redundant roles during embryonic development and in the larval
      nervous system. Ectopic expression studies demonstrate that the dNSF1 and dNSF2
      gene products can functionally substitute for one another. These results indicate
      that the Drosophila NSF proteins exhibit similar functional properties, but have
      evolved distinct tissue-specific roles.

PMID- 11333236
TI  - Evidence for selection at the fused1 locus of Drosophila americana.
AB  - We analyze genetic variation at fused1, a locus that is close to the centromere
      of the X chromosome-autosome (X/4) fusion in Drosophila americana. In contrast to
      other X-linked and autosomal genes, for which a lack of population subdivision in
      D. americana has been observed at the DNA level, we find strong haplotype
      structure associated with the alternative chromosomal arrangements. There are
      several derived fixed differences at fused1 (including one amino acid
      replacement) between two haplotype classes of this locus. From these results, we
      obtain an estimate of an age of approximately 0.61 million years for the origin
      of the two haplotypes of the fused1 gene. Haplotypes associated with the X/4
      fusion have less DNA sequence variation at fused1 than haplotypes associated with
      the ancestral chromosome arrangement. The X/4 haplotypes also exhibit clinal
      variation for the allele frequencies of the three most common amino acid
      replacement polymorphisms, but not for adjacent silent polymorphisms. These
      patterns of variation are best explained as a result of selection acting on amino
      acid substitutions, with geographic variation in selection pressures.

PMID- 11333239
TI  - Nonclinality of molecular variation implicates selection in maintaining a
      morphological cline of Drosophila melanogaster.
AB  - One general approach for assessing whether phenotypic variation is due to
      selection is to test its correlation with presumably neutral molecular variation.
      Neutral variation is determined by population history, the most likely
      alternative explanation of spatial genetic structure, whereas phenotypic
      variation may be influenced by the spatial pattern of selection pressure. Several
      methods for comparing the spatial apportionment of molecular and morphological
      variation have been used. Here, we present an analysis of variance framework that
      compares the magnitudes of latitudinal effects for molecular and morphological
      variation along a body size cline in Australian Drosophila populations. Explicit
      incorporation of the relevant environmental gradient can result in a simple and
      powerful test of selection. For the Australian cline, our analysis provides
      strong internal evidence that the cline is due to selection.

PMID- 11333238
TI  - Interactions between the inositol 1,4,5-trisphosphate and cyclic AMP signaling
      pathways regulate larval molting in Drosophila.
AB  - Larval molting in Drosophila, as in other insects, is initiated by the
      coordinated release of the steroid hormone ecdysone, in response to neural
      signals, at precise stages during development. In this study we have analyzed,
      using genetic and molecular methods, the roles played by two major signaling
      pathways in the regulation of larval molting in Drosophila. Previous studies have
      shown that mutants for the inositol 1,4,5-trisphosphate receptor gene (itpr) are
      larval lethals. In addition they exhibit delays in molting that can be rescued by
      exogenous feeding of 20-hydroxyecdysone. Here we show that mutants for adenylate
      cyclase (rut) synergize, during larval molting, with itpr mutant alleles,
      indicating that both cAMP and InsP(3) signaling pathways function in this
      process. The two pathways act in parallel to affect molting, as judged by
      phenotypes obtained through expression of dominant negative and dominant active
      forms of protein kinase A (PKA) in tissues that normally express the InsP(3)
      receptor. Furthermore, our studies predict the existence of feedback inhibition
      through protein kinase A on the InsP(3) receptor by increased levels of 20
      hydroxyecdysone.

PMID- 11333237
TI  - Long-range repression by multiple polycomb group (PcG) proteins targeted by
      fusion to a defined DNA-binding domain in Drosophila.
AB  - A tethering assay was developed to study the effects of Polycomb group (PcG)
      proteins on gene expression in vivo. This system employed the Su(Hw) DNA-binding
      domain (ZnF) to direct PcG proteins to transposons that carried the white and
      yellow reporter genes. These reporters constituted naive sensors of PcG effects,
      as bona fide PcG response elements (PREs) were absent from the constructs. To
      assess the effects of different genomic environments, reporter transposons
      integrated at nearly 40 chromosomal sites were analyzed. Three PcG fusion
      proteins, ZnF-PC, ZnF-SCM, and ZnF-ESC, were studied, since biochemical analyses
      place these PcG proteins in distinct complexes. Tethered ZnF-PcG proteins
      repressed white and yellow expression at the majority of sites tested, with each
      fusion protein displaying a characteristic degree of silencing. Repression by ZnF
      PC was stronger than ZnF-SCM, which was stronger than ZnF-ESC, as judged by the
      percentage of insertion lines affected and the magnitude of the conferred
      repression. ZnF-PcG repression was more effective at centric and telomeric
      reporter insertion sites, as compared to euchromatic sites. ZnF-PcG proteins
      tethered as far as 3.0 kb away from the target promoter produced silencing,
      indicating that these effects were long range. Repression by ZnF-SCM required a
      protein interaction domain, the SPM domain, which suggests that this domain is
      not primarily used to direct SCM to chromosomal loci. This targeting system is
      useful for studying protein domains and mechanisms involved in PcG repression in
      vivo.

PMID- 11333240
TI  - Multiple and independent cessation of recombination between avian sex
      chromosomes.
AB  - Birds are characterized by female heterogamety; females carry the Z and W sex
      chromosomes, while males have two copies of the Z chromosome. We suggest here
      that full differentiation of the Z and W sex chromosomes of birds did not take
      place until after the split of major contemporary lineages, in the late
      Cretaceous. The ATP synthase alpha-subunit gene is now present in one copy each
      on the nonrecombining part of the W chromosome (ATP5A1W) and on the Z chromosome
      (ATP5A1Z). This gene seems to have evolved on several independent occasions, in
      different lineages, from a state of free recombination into two sex-specific and
      nonrecombining variants. ATP5A1W and ATP5A1Z are thus more similar within orders,
      relative to what W (or Z) are between orders. Moreover, this cessation of
      recombination apparently took place at different times in different lineages
      (estimated at 13, 40, and 65 million years ago in Ciconiiformes, Galliformes, and
      Anseriformes, respectively). We argue that these observations are the result of
      recent and traceable steps in the process where sex chromosomes gradually cease
      to recombine and become differentiated. Our data demonstrate that this process,
      once initiated, may occur independently in parallel in sister lineages.

PMID- 11333241
TI  - Genetic architecture of testis and seminal vesicle weights in mice.
AB  - Comparisons across 13 inbred strains of laboratory mice for reproductive organ
      (paired seminal vesicles and paired testes) weights indicated a very marked
      contrast between the C57BL/6By and NZB/BINJ mice. Subsequently these strains were
      selected to perform a quantitative genetic analysis and full genome scan for
      seminal vesicle and testis weights. An F(2) population was generated. The
      quantitative genetic analyses indicated that each was linked to several genes.
      Sixty-six short sequences for length polymorphism were used as markers in the
      wide genome scan strategy. For weight of paired testes, heritability was 82.3% of
      the total variance and five QTL contributed to 72.8% of the total variance. Three
      reached a highly significant threshold (>4.5) and were mapped on chromosome X
      (LOD score 9.11), chromosome 4 (LOD score 5.96), chromosome 10 (LOD score 5.81);
      two QTL were suggested: chromosome 13 (LOD score 3.10) and chromosome 18 (LOD
      score 2.80). Heritability for weight of seminal vesicles was 50.7%. One QTL was
      mapped on chromosome 4 (LOD score 9.21) and contributed to 24.2% of the total
      variance. The distance of this QTL to the centromere encompassed the distance of
      the QTL linked with testicular weight on chromosome 4, suggesting common genetic
      mechanisms as expected from correlations in the F(2). Both testis and seminal
      vesicle weights were associated with a reduction in the NZB/BINJ when this strain
      carried the Y(NPAR) from CBA/H whereas the Y(NPAR) from NZB/BINJ in the CBA/H
      strain did not modify reproductive organ weights, indicating that the Y(NPAR)
      interacts with the non-Y(NPAR) genes. The effects generated by this chromosomal
      region were significant but small in size.

PMID- 11333242
TI  - Sequence and chromosomal context effects on variegated expression of keratin
      5/lacZ constructs in stratified epithelia of transgenic mice.
AB  - The expression of transgene loci in mammals often occurs in a heterocellular
      fashion resulting in variegated patterns of expression. We have examined the
      effect of chromosomal integration site, copy number, and transcriptionally
      activating sequences on the variegation of a keratin 5-lacZ (K5Z) construct in
      the stratified epithelia of transgenic mice. lacZ expression in these mice is
      always mosaic, and the beta-gal activity per cell is usually higher in the lines
      with a higher proportion of expressing cells. Similar constructs, in which cDNAs
      were exchanged by lacZ sequences, showed no variegation. Also, when a strongly
      active, nonvariegating construct was coinjected with K5Z, most transgenic lines
      showed an almost homogeneous lacZ expression. The comparison of transgene arrays
      of different copies inserted at the same locus (obtained by using a lox/Cre
      system) showed that the reduction of copy number does not lead to an increase in
      the proportion of cells that express the transgene. Finally, in most of the
      variegating or nonexpressing lines the transgenes were located both at
      intermediate positions and at peritelomeric regions in the long chromosome arms.
      These findings suggest that the probability and efficiency of expression of K5Z
      genes depend on both long range chromosomal influences and on sequences in the
      transgene array.

PMID- 11333243
TI  - Complete replacement of the mitochondrial genotype in a Bos indicus calf
      reconstructed by nuclear transfer to a Bos taurus oocyte.
AB  - Due to the exclusively maternal inheritance of mitochondria, mitochondrial
      genotypes can be coupled to a particular nuclear genotype by continuous mating of
      founder females and their female offspring to males of the desired nuclear
      genotype. However, backcrossing is a gradual procedure that, apart from being
      lengthy, cannot ascertain that genetic and epigenetic changes will modify the
      original nuclear genotype. Animal cloning by nuclear transfer using host ooplasm
      carrying polymorphic mitochondrial genomes allows, among other biotechnology
      applications, the coupling of nuclear and mitochondrial genotypes of diverse
      origin within a single generation. Previous attempts to use Bos taurus oocytes as
      hosts to transfer nuclei from unrelated species led to the development to the
      blastocyst stage but none supported gestation to term. Our aim in this study was
      to determine whether B. taurus oocytes support development of nuclei from the
      closely related B. indicus cattle and to examine the fate of their mitochondrial
      genotypes throughout development. We show that indicus:taurus reconstructed
      oocytes develop to the blastocyst stage and produce live offspring after transfer
      to surrogate cows. We also demonstrate that, in reconstructed embryos, donor cell
      derived mitochondria undergo a stringent genetic drift during early development
      leading, in most cases, to a reduction or complete elimination of B. indicus
      mtDNA. These results demonstrate that cross-subspecies animal cloning is a viable
      approach both for matching diverse nuclear and cytoplasmic genes to create novel
      breeds of cattle and for rescuing closely related endangered cattle.

PMID- 11333244
TI  - Statistical modeling of interlocus interactions in a complex disease: rejection
      of the multiplicative model of epistasis in type 1 diabetes.
AB  - In general, common diseases do not follow a Mendelian inheritance pattern. To
      identify disease mechanisms and etiology, their genetic dissection may be
      assisted by evaluation of linkage in mouse models of human disease. Statistical
      modeling of multiple-locus linkage data from the nonobese diabetic (NOD) mouse
      model of type 1 diabetes has previously provided evidence for epistasis between
      alleles of several Idd (insulin-dependent diabetes) loci. The construction of NOD
      congenic strains containing selected segments of the diabetes-resistant strain
      genome allows analysis of the joint effects of alleles of different loci in
      isolation, without the complication of other segregating Idd loci. In this
      article, we analyze data from congenic strains carrying two chromosome intervals
      (a double congenic strain) for two pairs of loci: Idd3 and Idd10 and Idd3 and
      Idd5. The joint action of both pairs is consistent with models of additivity on
      either the log odds of the penetrance, or the liability scale, rather than with
      the previously proposed multiplicative model of epistasis. For Idd3 and Idd5 we
      would also not reject a model of additivity on the penetrance scale, which might
      indicate a disease model mediated by more than one pathway leading to beta-cell
      destruction and development of diabetes. However, there has been confusion
      between different definitions of interaction or epistasis as used in the
      biological, statistical, epidemiological, and quantitative and human genetics
      fields. The degree to which statistical analyses can elucidate underlying
      biologic mechanisms may be limited and may require prior knowledge of the
      underlying etiology.

PMID- 11333245
TI  - DNA breaks in hypermutating immunoglobulin genes: evidence for a break-and-repair
      pathway of somatic hypermutation.
AB  - To test the hypothesis that immunoglobulin gene hypermutation in vivo employs a
      pathway in which DNA breaks are introduced and subsequently repaired to produce
      mutations, we have used a PCR-based assay to detect and identify single-strand
      DNA breaks in lambda1 genes of actively hypermutating primary murine germinal
      center B cells. We find that there is a two- to threefold excess of breaks in
      lambda1 genes of hypermutating B cells, relative to nonhypermutating B cells, and
      that 1.3% of germinal center B cells contain breaks in the lambda1 gene that are
      associated with hypermutation. Breaks were found in both top and bottom DNA
      strands and were localized to the region of lambda1 that actively hypermutates,
      but duplex breaks accounted for only a subset of breaks identified. Almost half
      of the breaks in hypermutating B cells occurred at hotspots, sites at which two
      or more independent breaks were identified. Breaksite hotspots were associated
      with characteristic sequence motifs: a pyrimidine-rich motif, either RCTYT or
      CCYC; and RGYW, a sequence motif associated with hypermutation hotspots. The
      sequence motifs identified at breaksite hotspots should inform the design of
      substrates for characterization of activities that participate in the
      hypermutation pathway.

PMID- 11333246
TI  - Characterization of the S-locus region of almond (Prunus dulcis): analysis of a
      somaclonal mutant and a cosmid contig for an S haplotype.
AB  - Almond has a self-incompatibility system that is controlled by an S locus
      consisting of the S-RNase gene and an unidentified "pollen S gene." An almond
      cultivar "Jeffries," a somaclonal mutant of "Nonpareil" (S(c)S(d)), has a
      dysfunctional S(c) haplotype both in pistil and pollen. Immunoblot and genomic
      Southern blot analyses detected no S(c) haplotype-specific signal in Jeffries.
      Southern blot showed that Jeffries has an extra copy of the S(d) haplotype. These
      results indicate that at least two mutations had occurred to generate Jeffries:
      (1) deletion of the S(c) haplotype and (2) duplication of the S(d) haplotype. To
      analyze the extent of the deletion in Jeffries and gain insight into the physical
      limit of the S locus region, approximately 200 kbp of a cosmid contig for the
      S(c) haplotype was constructed. Genomic Southern blot analyses showed that the
      deletion in Jeffries extends beyond the region covered by the contig. Most cosmid
      end probes, except those near the S(c)-RNase gene, cross-hybridized with DNA
      fragments from different S haplotypes. This suggests that regions away from the
      S(c)-RNase gene can recombine between different S haplotypes, implying that the
      cosmid contig extends to the borders of the S locus.

PMID- 11333247
TI  - Identification and characterization of a polymorphic receptor kinase gene linked
      to the self-incompatibility locus of Arabidopsis lyrata.
AB  - We study the segregation of variants of a putative self-incompatibility gene in
      Arabidopsis lyrata. This gene encodes a sequence that is homologous to the
      protein encoded by the SRK gene involved in self-incompatibility in Brassica
      species. We show by diallel pollinations of plants in several full-sib families
      that seven different sequences of the gene in A. lyrata are linked to different S
      alleles, and segregation analysis in further sibships shows that four other
      sequences behave as allelic to these. The family data on incompatibility provide
      evidence for dominance classes among the S-alleles, as expected for a sporophytic
      SI system. We observe no division into pollen-dominant and pollen-recessive
      classes of alleles as has been found in Brassica, but our alleles fall into at
      least three dominance classes in both pollen and stigma expression. The diversity
      among sequences of the A. lyrata putative S-alleles is greater than among the
      published Brassica SRK sequences, and, unlike Brassica, the alleles do not
      cluster into groups with similar dominance.

PMID- 11333248
TI  - Sequence diversity in the tetraploid Zea perennis and the closely related diploid
      Z. diploperennis: insights from four nuclear loci.
AB  - Polyploidy has been an extremely common phenomenon in the evolutionary history of
      angiosperms. Despite this there are few data available to evaluate the effects of
      polyploidy on genetic diversity and to compare the relative effects of drift and
      selection in polyploids and related diploids. We investigated DNA sequence
      diversity at four nuclear loci (adh1, glb1, c1, and waxy) from the tetraploid Zea
      perennis and the closely related diploid Z. diploperennis. Contrary to
      expectations, we detected no strong evidence for greater genetic diversity in the
      tetraploid, or for consistent differences in the effects of either drift or
      selection between the tetraploid and the diploid. Our failure to find greater
      genetic diversity in Z. perennis may result from its relatively recent origin or
      demographic factors associated with its origin. In addition to comparing genetic
      diversity in the two species, we constructed genealogies to infer the
      evolutionary origin of Z. perennis. Although these genealogies are equivocal
      regarding the mode of origin, several aspects of these genealogies support an
      autotetraploid origin. Consistent with previous molecular data the genealogies do
      not, however, support the division of Zea into two sections, the section Zea and
      the section Luxuriantes.

PMID- 11333249
TI  - Dissecting the genetic pathway to extreme fruit size in tomato using a cross
      between the small-fruited wild species Lycopersicon pimpinellifolium and L.
      esculentum var. Giant Heirloom.
AB  - In an effort to determine the genetic basis of exceptionally large tomato fruits,
      QTL analysis was performed on a population derived from a cross between the wild
      species Lycopersicon pimpinellifolium (average fruit weight, 1 g) and the L.
      esculentum cultivar var. Giant Heirloom, which bears fruit in excess of 1000 g.
      QTL analysis revealed that the majority (67%) of phenotypic variation in fruit
      size could be attributed to six major loci localized on chromosomes 1-3 and 11.
      None of the QTL map to novel regions of the genome-all have been reported in
      previous studies involving moderately sized tomatoes. This result suggests that
      no major QTL beyond those already reported were involved in the evolution of
      extremely large fruit. However, this is the first time that all six QTL have
      emerged in a single population, suggesting that exceptionally large-fruited
      varieties, such as Giant Heirloom, are the result of a novel combination of
      preexisting QTL alleles. One of the detected QTL, fw2.2, has been cloned and
      exerts its effect on fruit size through global control of cell division early in
      carpel/fruit development. However, the most significant QTL detected in this
      study (fw11.3, lcn11.1) maps to the bottom of chromosome 11 and seems to exert
      its effect on fruit size through control of carpel/locule number. A second major
      locus, also affecting carpel number (and hence fruit size), was mapped to
      chromosome 2 (fw2.1, lcn2.1). We propose that these two carpel number QTL
      correspond to the loci described by early classical geneticists as fasciated (f)
      and locule number (lc), respectively.

PMID- 11333250
TI  - Recombination between paralogues at the Rp1 rust resistance locus in maize.
AB  - Rp1 is a complex rust resistance locus of maize. The HRp1-D haplotype is composed
      of Rp1-D and eight paralogues, seven of which also code for predicted nucleotide
      binding site-leucine rich repeat (NBS-LRR) proteins similar to the Rp1-D gene.
      The paralogues are polymorphic (DNA identities 91-97%), especially in the C
      terminal LRR domain. The remaining family member encodes a truncated protein that
      has no LRR domain. Seven of the nine family members, including the truncated
      gene, are transcribed. Sequence comparisons between paralogues provide evidence
      for past recombination events between paralogues and diversifying selection,
      particularly in the C-terminal half of the LRR domain. Variants selected for
      complete or partial loss of Rp1-D resistance can be explained by unequal crossing
      over that occurred mostly within coding regions. The Rp1-D gene is altered or
      lost in all variants, the recombination breakpoints occur throughout the genes,
      and most recombinant events (9/14 examined) involved the same untranscribed
      paralogue with the Rp1-D gene. One recombinant with a complete LRR from Rp1-D,
      but the amino-terminal portion from another homologue, conferred the Rp1-D
      specificity but with a reduced level of resistance.

PMID- 11333251
TI  - The leucine-rich repeat domain can determine effective interaction between RPS2
      and other host factors in arabidopsis RPS2-mediated disease resistance.
AB  - Like many other plant disease resistance genes, Arabidopsis thaliana RPS2 encodes
      a product with nucleotide-binding site (NBS) and leucine-rich repeat (LRR)
      domains. This study explored the hypothesized interaction of RPS2 with other host
      factors that may be required for perception of Pseudomonas syringae pathogens
      that express avrRpt2 and/or for the subsequent induction of plant defense
      responses. Crosses between Arabidopsis ecotypes Col-0 (resistant) and Po-1
      (susceptible) revealed segregation of more than one gene that controls resistance
      to P. syringae that express avrRpt2. Many F(2) and F(3) progeny exhibited
      intermediate resistance phenotypes. In addition to RPS2, at least one additional
      genetic interval associated with this defense response was identified and mapped
      using quantitative genetic methods. Further genetic and molecular genetic
      complementation experiments with cloned RPS2 alleles revealed that the Po-1
      allele of RPS2 can function in a Col-0 genetic background, but not in a Po-1
      background. The other resistance-determining genes of Po-1 can function, however,
      as they successfully conferred resistance in combination with the Col-0 allele of
      RPS2. Domain-swap experiments revealed that in RPS2, a polymorphism at six amino
      acids in the LRR region is responsible for this allele-specific ability to
      function with other host factors.

PMID- 11333252
TI  - A test for transvection in plants: DNA pairing may lead to trans-activation or
      silencing of complex heteroalleles in tobacco.
AB  - To study whether DNA pairing that influences gene expression can take place in
      somatic plant cells, a system designed to mimic transvection was established in
      transgenic tobacco. Pairing was evaluated by testing whether an enhancerless GUS
      gene on one allele could be activated in trans by an enhancer on the second
      allele. The required heteroalleles were obtained at four genomic locations using
      Cre-lox-mediated recombination. In one transgenic line, elevated GUS activity was
      observed with the heteroallelic combination, suggesting that trans-activation
      occurred. Conversely, when the unaltered allele was homozygous, GUS activity
      dropped to hemizygous levels in a silencing phenomenon resembling dosage
      compensation. Double-stranded GUS RNAs or small GUS RNAs indicative of RNA-based
      silencing mechanisms were not detected in plants displaying reduced GUS activity.
      These results suggested that a transgene locus capable of pairing, as revealed by
      trans-activation, could also become silenced in an RNA-independent manner, thus
      linking DNA pairing and gene silencing. The transgene locus was complex and
      comprised an inverted repeat, which possibly potentiated allelic interactions.
      The locus was unable to trans-activate transgenes at ectopic sites, further
      implicating allelic pairing in the transvection effects.

PMID- 11333253
TI  - Detection of closely linked multiple quantitative trait loci using a genetic
      algorithm.
AB  - The existence of a quantitative trait locus (QTL) is usually tested using the
      likelihood of the quantitative trait on the basis of phenotypic character data
      plus the recombination fraction between QTL and flanking markers. When doing
      this, the likelihood is calculated for all possible locations on the linkage map.
      When multiple QTL are suspected close by, it is impractical to calculate the
      likelihood for all possible combinations of numbers and locations of QTL. Here,
      we propose a genetic algorithm (GA) for the heuristic solution of this problem.
      GA can globally search the optimum by improving the "genotype" with alterations
      called "recombination" and "mutation." The "genotype" of our GA is the number and
      location of QTL. The "fitness" is a function based on the likelihood plus
      Akaike's information criterion (AIC), which helps avoid false-positive QTL. A
      simulation study comparing the new method with existing QTL mapping packages
      shows the advantage of the new GA. The GA reliably distinguishes multiple QTL
      located in a single marker interval.

PMID- 11333254
TI  - Epistasis and the mutation load: a measurement-theoretical approach.
AB  - An approximate solution for the mean fitness in mutation-selection balance with
      arbitrary order of epistatic interaction is derived. The solution is based on the
      assumptions of coupling equilibrium and that the interaction effects are
      multilinear. We find that the effect of m-order epistatic interactions (i.e.,
      interactions among groups of m loci) on the load is dependent on the total
      genomic mutation rate, U, to the mth power. Thus, higher-order gene interactions
      are potentially important if U is large and the interaction density among loci is
      not too low. The solution suggests that synergistic epistasis will decrease the
      mutation load and that variation in epistatic effects will elevate the load. Both
      of these results, however, are strictly true only if they refer to epistatic
      interaction strengths measured in the optimal genotype. If gene interactions are
      measured at mutation-selection equilibrium, only synergistic interactions among
      even numbers of genes will reduce the load. Odd-ordered synergistic interactions
      will then elevate the load. There is no systematic relationship between variation
      in epistasis and load at equilibrium. We argue that empirical estimates of gene
      interaction must pay attention to the genetic background in which the effects are
      measured and that it may be advantageous to refer to average interaction
      intensities as measured in mutation-selection equilibrium. We derive a simple
      criterion for the strength of epistasis that is necessary to overcome the twofold
      disadvantage of sex.

PMID- 11333255
TI  - Rapid agonist-induced desensitization and internalization of the A(2B) adenosine
      receptor is mediated by a serine residue close to the COOH terminus.
AB  - The G(s)-coupled rat A(2B) adenosine receptor (A(2B)-AR) was epitope-tagged at
      the NH(2) terminus with hemagglutinin (HA) and subjected to progressive deletions
      or point mutations of the COOH terminus in order to determine regions of the
      receptor that contribute to agonist-induced desensitization and internalization.
      When expressed stably in Chinese hamster ovary cells, a mutant receptor in which
      the final 2 amino acids were deleted, the Leu(330)-stop mutant, underwent rapid
      agonist-induced desensitization and internalization as did the wild type (WT)
      receptor. However, the Phe(328) and the Gln(325)-stop mutants were resistant to
      rapid agonist-induced desensitization and internalization. Co-expression of
      arrestin-2-green fluorescent protein (arrestin-2-GFP) with WT receptor or
      Leu(330)-stop mutant resulted in rapid translocation of arrestin-2-GFP from
      cytosol to membrane upon agonist addition. On the other hand, agonist activation
      of the Phe(328)-stop or Gln(325)-stop mutant did not result in translocation of
      arrestin-2-GFP from cytosol. A COOH terminus point mutant, S329G, was also unable
      to undergo rapid agonist-induced desensitization and internalization, indicating
      that Ser(329) is a critical residue for these processes. A further deletion
      mutant (Ser(326)-stop) unexpectedly underwent rapid agonist-induced
      desensitization and internalization. However, activation of this mutant did not
      promote translocation of arrestin-2-GFP from cytosol to membrane. In addition,
      whereas WT receptor internalization was markedly inhibited by co-expression of
      dominant negative mutants of arrestin-2 (arrestin-2-(319-418)), dynamin (dynamin
      K44A), or Eps-15 (EDelta95-295), Ser(326)-stop receptor internalization was only
      inhibited by dominant negative mutant dynamin. Taken together these results
      indicate that Ser(329), close to the COOH terminus of the rat A(2B)-AR, is
      critical for the rapid agonist-induced desensitization and internalization of the
      receptor. However, deletion of the COOH terminus also uncovers a motif that is
      able to redirect internalization of the receptor to an arrestin- and clathrin
      independent pathway.

PMID- 11333256
TI  - D-Aspartate is stored in secretory granules and released through a Ca(2+)
      dependent pathway in a subset of rat pheochromocytoma PC12 cells.
AB  - D-Aspartate in mammalian neuronal and neuroendocrine cells is suggested to play a
      regulatory role(s) in the neuroendocrine function. Although D-aspartate is known
      to be released from neuroendocrine cells, the mechanism underlying the release is
      less understood. Rat pheochromocytoma PC12 cells contain an appreciable amount of
      D-aspartate (257 +/- 31 pmol/10(7) cells). Indirect immunofluorescence microscopy
      with specific antibodies against d-aspartate indicated that the amino acid is
      present within a particulate structure, which is co-localized with dopamine and
      chromogranin A, markers for secretory granules, but not with synaptophysin, a
      marker for synaptic-like microvesicles. After sucrose density gradient
      centrifugation of the postnuclear particulate fraction, about 80% of the d
      aspartate was recovered in the secretory granule fraction. Upon the addition of
      KCl, an appreciable amount of D-aspartate (about 40 pmol/10(7) cells at 10 min)
      was released from cultured cells on incubation in the presence of Ca(2+) in the
      medium. The addition of also triggered d-aspartate release. Botulinum neurotoxin
      type E inhibited about 40% of KCl- and Ca(2+)-dependent d-aspartate release
      followed by specific cleavage of 25-kDa synaptosomal-associated protein. alpha
      Latrotoxin increased the intracellular [Ca(2+)] and caused the Ca(2+)-dependent d
      aspartate release. Bafilomycin A1 dissipated the intracellular acidic regions and
      inhibited 40% of the Ca(2+)-dependent D-aspartate release. These properties are
      similar to those of the exocytosis of dopamine. Furthermore, digitonin
      permeabilized cells took up radiolabeled d-aspartate depending on MgATP, which is
      sensitive to bafilomycin A1 or 3,5-di-tert-butyl-4-hydroxybenzylidene
      malononitrile. Taken together, these results strongly suggest that d-aspartate is
      stored in secretory granules and then secreted through a Ca(2+)-dependent
      exocytotic mechanism. Exocytosis of D-aspartate further supports the role(s) of D
      aspartate as a chemical transmitter in neuroendocrine cells.

PMID- 11333257
TI  - Subcellular localization of the human proto-oncogene protein DEK.
AB  - Recent data revealed that DEK associates with splicing complexes through
      interactions mediated by serine/arginine-repeat proteins. However, the DEK
      protein has also been shown to change the topology of DNA in chromatin in vitro.
      This could indicate that the DEK protein resides on cellular chromatin. To
      investigate the in vivo localization of DEK, we performed cell fractionation
      studies, immunolabeling, and micrococcal nuclease digestion analysis. Most of the
      DEK protein was found to be released by DNase treatment of nuclei, and only a
      small amount by treatment with RNase. Furthermore, micrococcal nuclease digestion
      of nuclei followed by glycerol gradient sedimentation revealed that DEK co
      sedimentates with oligonucleosomes, clearly demonstrating that DEK is associated
      with chromatin in vivo. Additional chromatin fractionation studies, based on the
      different accessibilities to micrococcal nuclease, showed that DEK is associated
      both with extended, genetically active and more densely organized, inactive
      chromatin. We found no significant change in the amount and localization of DEK
      in cells that synchronously traversed the cell cycle. In summary these data
      demonstrate that the major portion of DEK is associated with chromatin in vivo
      and suggest that it might play a role in chromatin architecture.

PMID- 11333259
TI  - Apoprotein B degradation is promoted by the molecular chaperones hsp90 and hsp70.
AB  - Apoprotein B (apoB) is the major protein of liver-derived atherogenic
      lipoproteins. The net production of apoB can be regulated by presecretory
      degradation mediated by the ubiquitin-proteasome pathway and cytosolic hsp70. To
      further explore the mechanisms of apoB degradation, we have established a cell
      free system in which degradation can be faithfully recapitulated. Human apoB48
      synthesized in vitro was translocated into microsomes, glycosylated, and
      ubiquitinylated. Subsequent incubation with rat hepatic cytosol led to proteasome
      mediated degradation. To explore whether hsp90 is required for apoB degradation,
      geldanamycin (GA) was added during the degradation assay. GA increased the
      recovery of microsomal apoB48 approximately 3-fold and disrupted the interaction
      between hsp90 and apoB48. Confirming the hsp90 effect in the cell-free system, we
      also found that transfection of hsp90 cDNA into rat hepatoma cells enhanced
      apoB48 degradation. Finally, apoB48 degradation was reconstituted in vitro using
      cytosol prepared from wild type yeast. Notably, degradation was attenuated when
      apoB48-containing microsomes were incubated with cytosol supplemented with GA or
      with cytosol prepared from yeast strains with mutations in the homologues of
      mammalian hsp70 and hsp90. Overall, our data suggest that hsp90 facilitates the
      interaction between endoplasmic reticulum-associated apoB and components of the
      proteasomal pathway, perhaps in cooperation with hsp70.

PMID- 11333258
TI  - Sterol carrier protein-2 expression modulates protein and lipid composition of
      lipid droplets.
AB  - Despite the critical role lipid droplets play in maintaining energy reserves and
      lipid stores for the cell, little is known about the regulation of the lipid or
      protein components within the lipid droplet. Although immunofluorescence of
      intact cells as well as Western analysis of isolated lipid droplets revealed that
      sterol carrier protein-2 (SCP-2) was not associated with lipid droplets, SCP-2
      expression significantly altered the structure of the lipid droplet. First, the
      targeting of fatty acid and cholesterol to the lipid droplets was significantly
      decreased. Second, the content of several proteins important for lipid droplet
      function was differentially increased (perilipin A), reduced severalfold (adipose
      differentiation-related protein (ADRP), vimentin), or almost completely
      eliminated (hormone-sensitive lipase and proteins >93 kDa) in the isolated lipid
      droplet. Third, the distribution of lipids within the lipid droplets was
      significantly altered. Double labeling of cells with 12-(N-methyl)-N-[(7
      nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-octadecanoic acid (NBD-stearic acid) and
      antisera to ADRP showed that 70, 24, and 13% of lipid droplets contained ADRP,
      NBD-stearic acid, or both, respectively. SCP-2 expression decreased the level of
      ADRP in the lipid droplet but increased the proportion wherein ADRP and NBD
      stearic acid colocalized by 3-fold. SCP-2 expression also decreased the lipid
      droplet fatty acid and cholesterol mass (nmol/mg protein) by 5.2- and 6.6-fold,
      respectively. Finally, SCP-2 expression selectively altered the pattern of
      esterified fatty acids in favor of polyunsaturated fatty acids within the lipid
      droplet. Displacement studies showed differential binding affinity of ADRP for
      cholesterol and fatty acids. These data suggested that SCP-2 and ADRP play a
      significant role in regulating fatty acid and cholesterol targeting to lipid
      droplets as well as in determining their lipid and protein components.

PMID- 11333260
TI  - The Escherichia coli heat labile toxin binds to Golgi membranes and alters Golgi
      and cell morphologies using ADP-ribosylation factor-dependent processes.
AB  - The fate of the catalytic subunit of the Escherichia coli heat labile toxin
      (LTA(1)) was studied after expression in mammalian cells to assess the
      requirement for ADP-ribosylation factor (ARF) binding to localization and
      toxicity and ability to compete with endogenous ARF effectors. A progression in
      LTA(1) localization from cytosol to binding Golgi stacks to condensation of Golgi
      membranes was found to correlate with the time and level of LTA(1) expression. At
      the highest levels of LTA(1) expression the staining of LTA and both extrinsic
      and lumenal Golgi markers all became diffuse, in a fashion reminiscent of the
      actions of brefeldin A. Thus, LTA(1) binds to the Golgi and can alter its
      morphology in two distinct ways. However, point mutants of LTA(1) that are
      defective in the ability to bind activated ARF were also unable to bind Golgi
      membranes or modify Golgi morphology. Co-expression of mutants of ARF3 that
      regained binding to these same mutant LTA(1) proteins restored the localization
      and activities of the toxin. Thus, binding to ARF is required both for the
      localization of the toxin to the Golgi and for effects on Golgi membranes. A
      correlation was also seen between the ability of LTA mutants to bind ARF and the
      increase in cellular cAMP levels. These results demonstrate the importance of ARF
      binding to the toxicity and cellular effects of the ADP-ribosylating bacterial
      toxin and reveal that mutants defective in binding ARF retain basal ADP
      ribosylation activity but are the least toxic LTA(1) mutants yet described,
      making them the best candidates for development as mucosal adjuvants.

PMID- 11333261
TI  - Mitochondrial Ca(2+) uptake depends on the spatial and temporal profile of
      cytosolic Ca(2+) signals.
AB  - Using confocal imaging of Rhod-2-loaded HeLa cells, we examined the ability of
      mitochondria to sequester Ca(2+) signals arising from different sources.
      Mitochondrial Ca(2+) (Ca(2+)mit) uptake was stimulated by inositol 1,4,5
      trisphosphate (InsP(3))-evoked Ca(2+) release, capacitative Ca(2+) entry, and
      Ca(2+) leaking from the endoplasmic reticulum. For each Ca(2+) source, the
      relationship between cytosolic Ca(2+) (Ca(2+)cyt) concentration and Ca(2+)mit was
      complex. With Ca(2+)cyt < 300 nm, a slow and persistent Ca(2+)mit uptake was
      observed. If Ca(2+)cyt increased above approximately 400 nm, Ca(2+)mit uptake
      accelerated sharply. For equivalent Ca(2+)cyt increases, the rate of Ca(2+)mit
      rise was greater with InsP(3)-evoked Ca(2+) signals than any other source.
      Spatial variation of the Ca(2+)mit response was observed within individual cells.
      Both the fraction of responsive mitochondria and the amplitude of the Ca(2+)mit
      response were graded in direct proportion to stimulus concentration. Trains of
      repetitive Ca(2+) oscillations did not maintain elevated Ca(2+)mit levels. Only
      low frequency Ca(2+) transients (<1/15 min) evoked repetitive Ca(2+)mit signals.
      Our data indicate that there is a lag between Ca(2+)cyt and Ca(2+)mit increases
      but that mitochondria will accumulate calcium when it is elevated over basal
      levels regardless of its source. Furthermore, in addition to the characteristics
      of Ca(2+) signals, Ca(2+) uniporter desensitization and proximity of mitochondria
      to InsP(3) receptors modulate mitochondrial Ca(2+) responses.

PMID- 11333262
TI  - Fused p47phox and p67phox truncations efficiently reconstitute NADPH oxidase with
      higher activity and stability than the individual components.
AB  - Activation of the neutrophil NADPH oxidase occurs via assembly of the cytosolic
      regulatory proteins p47(phox), p67(phox), and Rac with the membrane-associated
      flavocytochrome b(558). Following cell-free activation, enzymatic activity is
      highly labile (Tamura, M., Takeshita, M., Curnutte, J. T., Uhlinger, D. J., and
      Lambeth, J. D. (1992) J. Biol. Chem. 267, 7529-7538). To try to stabilize the
      activity and investigate the nature of the complex, fusion proteins between p47N
      (1-286) and p67N-(1-210) were constructed. In a cell-free system, a fusion
      protein, p67N-p47N, had an 8-fold higher efficiency and produced a higher
      activity than the individual proteins, and also resulted in an 8-fold improved
      efficiency for Rac and a lowered K(m) for NADPH. O(2) generating activity was
      remarkably stabilized by using p67N-p47N. The cytosolic proteins fused in the
      opposite orientation, p47N-p67N, showed similar activity and stability as
      individual proteins, but with a 4-fold improved efficiency compared with the
      individual cytosolic factors. In the system efficiency for Rac and affinity for
      NADPH were also higher than those with the nonfused components. Interestingly,
      the p67N-p47N showed nearly full activation in the absence of an anionic
      amphifile in a cell-free system containing cytochrome b(558) relipidated with
      phosphatidylinositol- or phosphatidylserine-enriched phospholipid mixtures. From
      the results we consider multiple roles of anionic amphifiles in a cell-free
      activation, which could be substituted by our system. The fact that a fusion
      produces a more stable complex indicates that interactions among components
      determine the longevity of the complex. Based on the findings we propose a model
      for the topology among p47N, p67N, and cytochrome b(558) in the active complex.

PMID- 11333263
TI  - An E-box motif residing in the exon/intron 1 junction regulates both
      transcriptional activation and splicing of the human norepinephrine transporter
      gene.
AB  - The norepinephrine transporter (NET) is responsible for the rapid NaCl-dependent
      uptake of norepinephrine into presynaptic noradrenergic nerve endings. Recently,
      we have characterized the structural organization of the 5' upstream promoter
      region of the human NET (hNET) gene. A new intron of 476 base pairs was found in
      the middle of the 5'-untranslated leader sequence and was shown to robustly
      enhance the promoter activity. Here, we show that the first hNET intron enhances
      both the homologous hNET and the heterologous thymidine kinase promoter
      activities in an orientation- and position-dependent manner. The first hNET
      intron exhibited a similar promoter-enhancing effect in both SK-N-BE(2)C (NET
      positive) and HeLa (NET-negative) cell lines, showing that its function is not
      cell-specific. Transient transfection assays of a series of deletional constructs
      show that the first hNET intron contains subdomains with either positive or
      negative regulatory functions. Furthermore, DNase I footprinting analysis
      demonstrated that the 5' side of the intron, encompassing the splice donor site,
      is prominently protected by nuclear proteins isolated from both SK-N-BE(2)C and
      HeLa cells. The protected nucleotide sequence contains a consensus E-box motif,
      known to regulate diverse eukaryotic genes, which overlaps with the splice donor
      site of the first intron. We demonstrate that two basic helix-loop-helix
      proteins, upstream stimulatory factors 1 and 2, are major proteins interacting at
      this site and that the E-box is at least in part responsible for the promoter
      enhancing activity of the first intron. Furthermore, site-directed mutagenesis of
      the splice donor site of the first intron affects both correct splicing and
      transcriptional activity. Taken together, our results indicate that a cis-element
      residing at the first exon/intron junction, encompassing an E-box motif, has a
      unique dual role in basal transcriptional activation and splicing of hNET mRNA.

PMID- 11333264
TI  - Multistep chromatin assembly on supercoiled plasmid DNA by nucleosome assembly
      protein-1 and ATP-utilizing chromatin assembly and remodeling factor.
AB  - We examine in vitro nucleosome assembly by nucleosome assembly protein-1 (NAP-1)
      and ATP-utilizing chromatin assembly and remodeling factor (ACF). In contrast to
      previous studies that used relaxed, circular plasmids as templates, we have found
      that negatively supercoiled templates reveal the distinct roles of NAP-1 and ACF
      in histone deposition and the formation of an ordered nucleosomal array. NAP-1
      can efficiently deposit histones onto supercoiled plasmids. Furthermore, NAP-1
      exhibits a greater affinity for histones H2A-H2B than does naked DNA, but in the
      presence of H3-H4, H2A-H2B are transferred from NAP-1 to the plasmid templates.
      These observations underscore the importance of a high affinity between H2A-H2B
      and NAP-1 for ordered transfer of core histones onto DNA. In addition,
      recombinant ACF composed of imitation switch and Acf1 can extend closely packed
      nucleosomes, which suggests that recombinant ACF can mobilize nucleosomes. In the
      assembly reaction with a supercoiled template, ACF need not be added
      simultaneously with NAP-1. Regularly spaced nucleosomes are generated even when
      recombinant ACF is added after core histones are transferred completely onto the
      DNA. Atomic force microscopy, however, suggests that NAP-1 alone fails to
      accomplish the formation of fine nucleosomal core particles, which are only
      formed in the presence of ACF. These results suggest a model for the ordered
      deposition of histones and the arrangement of nucleosomes during chromatin
      assembly in vivo.

PMID- 11333265
TI  - Molecular cloning and characterization of a novel human galactose 3-O
      sulfotransferase that transfers sulfate to gal beta 1-->3galNAc residue in O
      glycans.
AB  - We have identified a novel galactose 3-O-sulfotransferase, termed Gal3ST-4, by
      analysis of an expression sequence tag using the amino acid sequence of human
      cerebroside 3'-sulfotransferase (Gal3ST-1). The isolated cDNA contains a single
      open reading frame coding for a protein of 486 amino acids with a type II
      transmembrane topology. The amino acid sequence of Gal3ST-4 revealed 33%, 39%,
      and 30% identity to human Gal3ST-1, Gal beta 1-->3/4GlcNAc:-->3'-sulfotransferase
      (Gal3ST-2) and Gal beta 1-->4GlcNAc:-->3'-sulfotransferase (Gal3ST-3),
      respectively. The Gal3ST-4 gene comprised at least four exons and was located on
      human chromosome 7q22. Expression of Gal3ST-4 in COS-7 cells produced a
      sulfotransferase activity that catalyzes the transfer of [(35)S]sulfate to the C
      3' position of Gal beta 1-->3GalNAc alpha 1-O-Bn. Gal3ST-4 recognizes Gal beta 1-
      >3GalNAc and Gal beta 1-->3(GlcNAc beta 1-->6)GalNAc as good substrates, but not
      Gal beta 1-->3GalNAc(OH) or Gal beta 1-->3/4GlcNAc. Asialofetuin is also a good
      substrate, and the sulfation was found exclusively in O-linked glycans that
      consist of the Gal beta 1-->3GalNAc moiety, suggesting that the enzyme is
      specific for O-linked glycans. Northern blot analysis revealed that 2.5-kilobase
      mRNA for the enzyme is expressed extensively in various tissues. These results
      suggest that Gal3ST-4 is the fourth member of a Gal:-->3-sulfotransferase family
      and that the four members, Gal3ST-1, Gal3ST-2, Gal3ST-3, and Gal3ST-4, are
      responsible for sulfation of different acceptor substrates.

PMID- 11333266
TI  - Anandamide activates vanilloid receptor 1 (VR1) at acidic pH in dorsal root
      ganglia neurons and cells ectopically expressing VR1.
AB  - The vanilloid receptor type 1 (VR1) is a heat-activated ionophore preferentially
      expressed in nociceptive neurons of trigeminal and dorsal root ganglia (DRG).
      VR1, which binds and is activated by capsaicin and other vanilloid compounds, was
      noted to interact with the endocannabinoid anandamide (ANA) and certain
      inflammatory metabolites of arachidonic acid in a pH-dependent manner. At pH < or
      = 6.5 ANA induced (45)Ca(2+) uptake either in primary cultures of DRG neurons or
      cells ectopically expressing C-terminally tagged recombinant forms of VR1 with an
      EC(50) = approximately 10 microm at pH 5.5. Capsazepine, a potent antagonist of
      vanilloids, inhibited ANA-induced Ca(2+) transport in both cell systems.
      Vanilloids displaced [(3)H]ANA in VR1-expressing cells, suggesting competition
      for binding to VR1. Ratiometric determination of intracellular free calcium and
      confocal imaging of the VR1-green fluorescent fusion protein revealed that, at
      low pH (< or =6.5), ANA could induce an elevation of intracellular free Ca(2+)
      and consequent intracellular membrane changes in DRG neurons or transfected cells
      expressing VR1. These actions of ANA were similar to the effects determined
      previously for vanilloids. The ligand-induced changes in Ca(2+) at pH < or = 6.5
      are consistent with the idea that ANA and other eicosanoids act as endogenous
      ligands of VR1 in a conditional fashion in vivo. The pH dependence suggests that
      tissue acidification in inflammation, ischemia, or traumatic injury can sensitize
      VR1 to eicosanoids and transduce pain from the periphery.

PMID- 11333267
TI  - Xenopus rhodopsin promoter. Identification of immediate upstream sequences
      necessary for high level, rod-specific transcription.
AB  - To understand the mechanisms that control the cell-specific visual pigment gene
      transcription, the Xenopus rhodopsin 5' regulatory region has been characterized
      in vivo using transient transfection of Xenopus embryos and transgenesis. The
      principal control sequences were located within -233/+41, a region with
      significant conservation with mammalian rhodopsin genes. DNase footprinting
      indicated seven distinct regions that contain potential cis-acting elements.
      Sequences near the initiation site (-45/+41, basal region) were essential, but
      not sufficient, for rod-specific transcription. Two negative regulatory regions
      were found, one between -233 to -202, with no apparent similarity to known
      elements, and a second Ret-1-like CAAT (-136/-122) motif. Deletion of either
      sequence led to a 2-3-fold increase in expression levels, without a change in rod
      specificity. Sequences between -170 to -146, which contain an E-box motif, were
      necessary for high level expression in transgenic tadpoles but not in transient
      transfections. Sequences between -84 and -58, which contained an NRE-like
      consensus were found to be necessary for high level expression in both assays.
      Although expression levels were modulated by various proximal sequences in the
      rhodopsin promoter, none of the tested sequences were found to be necessary for
      rod specificity. Promoter constructs with a consensus BAT-1 sequence in
      conjunction with an NRE-like element upstream of the basal promoter directed low
      level green fluorescent protein expression in the central nervous system in
      transgenic tadpoles. These results suggest that rod cell-specific expression of
      rhodopsin is controlled by redundant elements in the proximal promoter.

PMID- 11333268
TI  - Structure-based mutagenesis reveals distinct functions for Ras switch 1 and
      switch 2 in Sos-catalyzed guanine nucleotide exchange.
AB  - Ras GTPases function as binary switches in signaling pathways controlling cell
      growth and differentiation. The guanine nucleotide exchange factor Sos mediates
      the activation of Ras in response to extracellular signals. We have previously
      solved the crystal structure of nucleotide-free Ras in complex with the catalytic
      domain of Sos (Boriack-Sjodin, P. A., Margarit, S. M., Bar-Sagi, D., and Kuriyan,
      J. (1998) Nature 394, 337-343). The structure demonstrates that Sos induces
      conformational changes in two loop regions of Ras known as switch 1 and switch 2.
      In this study, we have employed site-directed mutagenesis to investigate the
      functional significance of the conformational changes for the catalytic function
      of Sos. Switch 2 of Ras is held in a very tight embrace by Sos, with almost every
      external side chain coordinated by Sos. Mutagenesis of contact residues at the
      switch 2-Sos interface shows that only a small set of side chains affect binding,
      with the most important contact being mediated by tyrosine 64, which is buried in
      a hydrophobic pocket of Sos in the Ras.Sos complex. Substitutions of Ras and Sos
      side chains that are inserted into the Mg(2+)- and nucleotide phosphate-binding
      site of switch 2 (Ras Ala(59) and Sos Leu(938) and Glu(942)) have no effect on
      the catalytic function of Sos. These results indicate that the interaction of Sos
      with switch 2 is necessary for tight binding, but is not the critical driving
      force for GDP displacement. The structural distortion of switch 1 induced by Sos
      is mediated by a small number of specific contacts between highly conserved
      residues on both Ras and Sos. Mutations of a subset of these residues (Ras
      Tyr(32) and Tyr(40)) result in an increase in the intrinsic rate of nucleotide
      dissociation from Ras and impair the binding of Ras to Sos. Based on this
      analysis, we propose that the interactions of Sos with the switch 1 and switch 2
      regions of Ras have distinct functional consequences: the interaction with switch
      2 mediates the anchoring of Ras to Sos, whereas the interaction with switch 1
      leads to disruption of the nucleotide-binding site and GDP dissociation.

PMID- 11333269
TI  - Essential amino acids of Escherichia coli DnaC protein in an N-terminal domain
      interact with DnaB helicase.
AB  - Escherichia coli DnaC protein bound to ATP forms a complex with DnaB protein. To
      identify the domain of DnaC that interacts with DnaB, a genetic selection was
      used based on the lethal effect of induced dnaC expression and a model that
      inviability arises by the binding of DnaC to DnaB to inhibit replication fork
      movement. The analysis of dnaC alleles that preserved viability under elevated
      expression revealed an N-terminal domain of DnaC involved in binding to DnaB.
      Mutant proteins bearing single amino acid substitutions (R10P, L11Q, L29Q, S41P,
      W32G, and L44P) that reside in regions of predicted secondary structure were
      inert in DNA replication activity because of their inability to bind to DnaB, but
      they retained ATP binding activity, as indicated by UV cross-linking to [alpha
      (32)P]ATP. These alleles also failed to complement a dnaC28 mutant. Other
      selected mutations that map to regions carrying Walker A and B boxes are expected
      to be defective in ATP binding, a required step in DnaB-DnaC complex formation.
      Lastly, we found that the sixth codon from the N terminus encodes aspartate,
      resolving a reported discrepancy between the predicted amino acid sequence based
      on DNA sequencing data and the results from N-terminal amino acid sequencing
      (Nakayama, N., Bond, M. W., Miyajima, A., Kobori, J., and Arai, K. (1987) J.
      Biol. Chem. 262, 10475-10480).

PMID- 11333270
TI  - A signaling pathway from the alpha5beta1 and alpha(v)beta3 integrins that
      elevates bcl-2 transcription.
AB  - Integrin-mediated cell adhesion is necessary for the survival of many cell types,
      and loss of adhesion causes apoptosis. We have previously shown that the
      alpha5beta1 integrin supports cell survival on fibronectin and increases Bcl-2
      protein expression. Here we show that bcl-2 transcription is elevated in cells
      that attach to fibronectin through alpha(v)beta1 or to vitronectin through
      alpha(v)beta3 but is not elevated in cells attaching through the alpha(v)beta1
      integrin. Bcl-2 protein expression and protection from apoptosis under serum-free
      conditions correlated with bcl-2 transcription. This integrin-mediated regulation
      of bcl-2 is Shc- and FAK-dependent, and activation of Ras by FAK is required.
      Furthermore, Ras mediates this up-regulation of bcl-2 by activating the
      phosphatidylinositol 3-kinase-AKT pathway. Mitogen-activated protein kinase did
      not appear to be necessary for the activation of bcl-2 transcription. Therefore,
      our work characterizes the pathway that mediates the effect of integrins on bcl-2
      transcription and cell survival.

PMID- 11333272
TI  - HSP47 binds cooperatively to triple helical type I collagen but has little effect
      on the thermal stability or rate of refolding.
AB  - HSP47, a collagen-specific molecular chaperone, interacts with unfolded and
      folded procollagens. Binding of chicken HSP47 to native bovine type I collagen
      was studied by fluorescence quenching and cooperative binding with a collagen
      concentration at half saturation (K(half)) of 1.4 x 10(-7) m, and a Hill
      coefficient of 4.3 was observed. Similar results are observed for the binding of
      mouse HSP47 recombinantly expressed in Escherichia coli. Chicken HSP47 binds
      equally well to native type II and type III procollagen without the carboxyl
      terminal propeptide (pN type III collagen), but binding to triple helical
      collagen-like peptides is much weaker. Weak binding occurred to both hydroxylated
      and nonhydroxylated collagen-like peptides, and a significant chain length
      dependence was observed. Binding of HSP47 to native type I collagen had no effect
      on the thermal stability of the triple helix. Refolding of type I collagen in the
      presence of HSP47 showed minor changes, but these are probably not biologically
      significant. Binding of HSP47 to bovine pN type III collagen has only minor
      effects on the thermal stability of the triple helix and does not influence the
      refolding kinetics of the triple helix.

PMID- 11333271
TI  - Vascular endothelial growth factor receptor-2 and neuropilin-1 form a receptor
      complex that is responsible for the differential signaling potency of VEGF(165)
      and VEGF(121).
AB  - The two most abundant secreted isoforms of vascular endothelial growth factor A
      (VEGF(165) and VEGF(121)) are formed as a result of differential splicing of the
      VEGF-A gene. VEGF(165) and VEGF(121) share similar affinities at the isolated
      VEGF receptor (VEGFR)-2 but have been previously demonstrated to have
      differential ability to activate VEGFR-2-mediated effects on endothelial cells.
      Herein we investigate whether the recently described VEGF(165) isoform-specific
      receptor neuropilin-1 (Npn-1) is responsible for the difference in potency
      observed for these ligands. We demonstrate that although VEGFR-2 and Npn-1 form a
      complex, this complex does not result in an increase in VEGF(165) binding
      affinity. Therefore, the differential activity of VEGF(165) and VEGF(121) cannot
      be explained by a differential binding affinity for the complex. Using an
      antagonist that competes for VEGF(165) binding at the VEGFR-2.Npn-1 complex, we
      observe specific antagonism of VEGF(165)-meditated phosphorylation of VEGFR-2
      without affecting the VEGF(121) response. These data indicate that the formation
      of the complex is responsible for the increased potency of VEGF(165) versus
      VEGF(121). Taken together, these data suggest a receptor-clustering role for Npn
      1, as opposed to Npn-1 behaving as an affinity-converting subunit.

PMID- 11333273
TI  - Transactivation specificity of glucocorticoid versus progesterone receptors. Role
      of functionally different interactions of transcription factors with amino- and
      carboxyl-terminal receptor domains.
AB  - A major unanswered question of glucocorticoid and progesterone action is how
      different whole cell responses arise when both of the cognate receptors can bind
      to, and activate, the same hormone response elements. We have documented
      previously that the EC(50) of agonist complexes, and the partial agonist activity
      of antagonist complexes, of both glucocorticoid receptors (GRs) and progesterone
      receptors (PRs) are modulated by increased amounts of homologous receptor and of
      coregulators. We now ask whether these components can differentially alter GR and
      PR transcriptional properties. To remove possible cell-specific differences, we
      have examined both receptors in the common environment of a line of mouse mammary
      adenocarcinoma (1470.2) cells. In order to segregate the responses that might be
      due to unequal nucleosome reorganization by the two receptors from those
      reflecting interactions with other components, we chose a transiently transfected
      reporter containing a simple glucocorticoid response element (i.e. GREtkLUC). No
      significant differences are found with elevated levels of either receptor.
      However, major, qualitative differences are seen with the corepressors SMRT and
      NCoR, which afford opposite responses with GR and PR. Studies with chimeric GR/PR
      receptors indicate that no one segment of PR or GR is responsible for these
      properties and that the composite response likely involves interactions with both
      the amino and carboxyl termini of receptors. Collectively, the data suggest that
      GR and PR induction of responsive genes in a given cell can be differentially
      controlled, in part, by unequal interactions of multiple receptor domains with
      assorted nuclear cofactors.

PMID- 11333274
TI  - CYP83b1 is the oxime-metabolizing enzyme in the glucosinolate pathway in
      Arabidopsis.
AB  - CYP83B1 from Arabidopsis thaliana has been identified as the oxime-metabolizing
      enzyme in the biosynthetic pathway of glucosinolates. Biosynthetically active
      microsomes isolated from Sinapis alba converted p-hydroxyphenylacetaldoxime and
      cysteine into S-alkylated p-hydroxyphenylacetothiohydroximate, S-(p
      hydroxyphenylacetohydroximoyl)-l-cysteine, the next proposed intermediate in the
      glucosinolate pathway. The production was shown to be dependent on a cytochrome
      P450 monooxygenase. We searched the genome of A. thaliana for homologues of
      CYP71E1 (P450ox), the only known oxime-metabolizing enzyme in the biosynthetic
      pathway of the evolutionarily related cyanogenic glucosides. By a combined use of
      bioinformatics, published expression data, and knock-out phenotypes, we
      identified the cytochrome P450 CYP83B1 as the oxime-metabolizing enzyme in the
      glucosinolate pathway as evidenced by characterization of the recombinant protein
      expressed in Escherichia coli. The data are consistent with the hypothesis that
      the oxime-metabolizing enzyme in the cyanogenic pathway (P450ox) was mutated into
      a "P450mox" that converted oximes into toxic compounds that the plant detoxified
      into glucosinolates.

PMID- 11333275
TI  - Promoter regulatory elements and DNase I-hypersensitive sites involved in
      serglycin proteoglycan gene expression in human erythroleukemia, CHRF 288-11, and
      HL-60 cells.
AB  - We have compared regulation of the serglycin gene in human erythroleukemia (HEL)
      and CHRF 288-11 cells, which have megakaryocytic characteristics, with
      promyelocytic HL-60 cells. Deletion constructs were prepared from the region 
      1123/+42 to -20/+42, and putative regulatory sites were mutated. In all three
      cell lines, the two major regulatory elements for constitutive expression were
      the (-80)ets site and the cyclic AMP response element (CRE) half-site at -70. A
      protein from HEL and CHRF, but not HL60, nuclear extracts bound to the (-80)ets
      site. Another protein from all three cell lines bound to the (-70)CRE. Phorbol 12
      myristate 13-acetate (PMA) and dibutyryl cyclic AMP (dbcAMP) increased expression
      of the reporter in HEL cells 2.5-3- and 4.5-fold, respectively, from all
      constructs except those with (-70)CRE mutations. PMA virtually eliminated
      expression of serglycin mRNA and promoter constructs, but dbcAMP increased
      expression in HL-60 cells. The effects of PMA and dbcAMP on promoter expression
      correlated with mRNA expression. The strengths of two DNase I-hypersensitive
      sites in the 5'-flanking region and the first intron in all three cells
      correlated with relative endogenous serglycin mRNA expression. An additional
      DNase I-hypersensitive site in HL60 DNA in the first intron may be related to the
      high serglycin expression in HL60 relative to HEL or CHRF cells.

PMID- 11333276
TI  - Inhibition of anti-IgM-induced translocation of protein kinase C beta I inhibits
      ERK2 activation and increases apoptosis.
AB  - Expression of the COOH-terminal residues 179-330 of the LSP1 protein in the
      LSP1(+) B-cell line W10 increases anti-IgM- or ionomycin-induced apoptosis,
      suggesting that expression of this LSP1 truncate (B-LSP1) interferes with a
      Ca(2+)-dependent step in anti-IgM signaling. Here we show that inhibition of
      Ca(2+)-dependent conventional protein kinase C (cPKC) isoforms with Go6976
      increases anti-IgM-induced apoptosis of W10 cells and that expression of B-LSP1
      inhibits translocation of PKCbetaI but not of PKCbetaII or PKCalpha to the plasma
      membrane. The increased anti-IgM-induced apoptosis is partially reversed by
      overexpression of PKCbetaI. This shows that the B-LSP1-mediated inhibition of
      PKCbetaI leads to increased anti-IgM-induced apoptosis. Expression of
      constitutively active PKCbetaI protein in W10 cells activates the mitogen
      activated protein kinase ERK2, whereas expression of B-LSP1 inhibits anti-IgM
      induced activation of ERK2, suggesting that anti-IgM-activated PKCbetaI is
      involved in the activation of ERK2 and that inhibition of ERK2 activation
      contributes to the increased anti-IgM-induced apoptosis. Pull-down assays show
      that LSP1 interacts with PKCbetaI but not with PKCbetaII or PKCalpha in W10 cell
      lysates, while in vitro LSP1 and B-LSP1 bind directly to PKCbetaI. Thus, B-LSP1
      is a unique reagent that binds PKCbetaI and inhibits anti-IgM-induced PKCbetaI
      translocation, leading to inhibition of ERK2 activation and increased apoptosis.

PMID- 11333277
TI  - Tamoxifen: five versus ten years--is the end in sight?

PMID- 11333278
TI  - Promoter hypermethylation--can this change alone ever designate true tumor
      suppressor gene function?

PMID- 11333280
TI  - IOM report calls for improvements in health care system.

PMID- 11333281
TI  - Drop in cotinine levels signals less smoke exposure, experts say.

PMID- 11333279
TI  - p53 in Mammary ductal carcinoma in situ, mutations in high-grade lesions only?

PMID- 11333283
TI  - New Cancer Institute sets out to coordinate, promote research.

PMID- 11333286
TI  - Shared decision-making still evolving in cancer screening.

PMID- 11333287
TI  - Barrett's esophagus: major issues uncertain and unsolved.

PMID- 11333288
TI  - Virtual reality may help children undergoing chemotherapy.

PMID- 11333289
TI  - Recent trends in cutaneous melanoma incidence among whites in the United States.
AB  - BACKGROUND: It is not yet clear whether increasing melanoma incidence is real or
      whether recent incidence trends mainly reflect improved diagnosis. To address
      this question, we examined the most recent melanoma incidence patterns among the
      white population stratified by sex, age, tumor stage, and tumor thickness by use
      of data from the Surveillance, Epidemiology, and End Results Program. METHODS: We
      examined log-transformed age-specific rates for melanoma by 5-year age groups and
      time periods by year of diagnosis and birth cohort. Melanoma trends were further
      examined among broader age groups (<40 years, 40-59 years, and > or =60 years) by
      tumor stage and tumor thickness. Rates were age-adjusted to the 1970 U.S.
      standard population, and trends were tested by use of a two-sided Student's t
      test. RESULTS: Melanoma incidence increased in females born since the 1960s. From
      1974-1975 through 1988-1989, upward trends for the incidence of localized tumors
      and downward trends for the incidence of distant-stage tumors occurred in the age
      group under 40 years. In the more recent time period, 1990-1991 through 1996
      1997, age specific rates among females compared with males generally remained
      stable or declined more for distant-stage tumors and increased less for local
      stage tumors. Thin tumors (<1 mm) increased statistically significantly in all
      age groups (P<.05 for all), except in men under age 40 years. In contrast, rates
      for thick tumors (> or =4 mm) increased statistically significantly (P =.0003)
      only in males aged 60 years and older. CONCLUSION: Melanoma incidence may well
      continue to rise in the United States, at least until the majority of the current
      population in the middle-age groups becomes the oldest population. The recent
      trends may reflect increased sunlight exposure.

PMID- 11333290
TI  - Five versus more than five years of tamoxifen for lymph node-negative breast
      cancer: updated findings from the National Surgical Adjuvant Breast and Bowel
      Project B-14 randomized trial.
AB  - BACKGROUND: Previously reported information from B-14, a National Surgical
      Adjuvant Breast and Bowel Project (NSABP) randomized, placebo-controlled clinical
      trial, demonstrated that patients with estrogen receptor (ER)-positive breast
      cancer and negative axillary lymph nodes experienced a prolonged benefit from 5
      years of tamoxifen therapy. When these women were rerandomized to receive either
      placebo or more prolonged tamoxifen therapy, they obtained no additional
      advantage from tamoxifen through 4 years of follow-up. Because the optimal
      duration of tamoxifen administration continues to be controversial and because
      there have been 3 more years of follow-up and a substantial increase in the
      number of events since our last report, an update of the B-14 study is
      appropriate. METHODS: Patients (n = 1172) who had completed 5 years of tamoxifen
      therapy and who were disease free were rerandomized to receive placebo (n = 579)
      or tamoxifen (n = 593). Survival, disease-free survival (DFS), and relapse-free
      survival (RFS) were estimated by the Kaplan-Meier method; the differences between
      the treatment groups were assessed by the log-rank test. Relative risks of
      failure (with 95% confidence intervals) were determined by the Cox proportional
      hazards model. P values were two-sided. RESULTS: Through 7 years after
      reassignment of tamoxifen-treated patients to either placebo or continued
      tamoxifen therapy, a slight advantage was observed in patients who discontinued
      tamoxifen relative to those who continued to receive it: DFS = 82% versus 78% (P
      =.03), RFS = 94% versus 92% (P =.13), and survival = 94% versus 91% (P =.07),
      respectively. The lack of benefit from additional tamoxifen therapy was
      independent of age or other characteristics. CONCLUSION: Through 7 years of
      follow-up after rerandomization, there continues to be no additional benefit from
      tamoxifen administered beyond 5 years in women with ER-positive breast cancer and
      negative axillary lymph nodes.

PMID- 11333291
TI  - Epigenetic inactivation of RASSF1A in lung and breast cancers and malignant
      phenotype suppression.
AB  - BACKGROUND: The recently identified RASSF1 locus is located within a 120-kilobase
      region of chromosome 3p21.3 that frequently undergoes allele loss in lung and
      breast cancers. We explored the hypothesis that RASSF1 encodes a tumor suppressor
      gene for lung and breast cancers. METHODS: We assessed expression of two RASSF1
      gene products, RASSF1A and RASSF1C, and the methylation status of their
      respective promoters in 27 non-small-cell lung cancer (NSCLC) cell lines, in 107
      resected NSCLCs, in 47 small-cell lung cancer (SCLC) cell lines, in 22 breast
      cancer cell lines, in 39 resected breast cancers, in 104 nonmalignant lung
      samples, and in three breast and lung epithelial cultures. We also transfected a
      lung cancer cell line that lacks RASSF1A expression with vectors containing
      RASSF1A complementary DNA to determine whether exogenous expression of RASSF1A
      would affect in vitro growth and in vivo tumorigenicity of this cell line. All
      statistical tests were two-sided. RESULTS: RASSF1A messenger RNA was expressed in
      nonmalignant epithelial cultures but not in 100% of the SCLC, in 65% of the
      NSCLC, or in 60% of the breast cancer lines. By contrast, RASSF1C was expressed
      in all nonmalignant cell cultures and in nearly all cancer cell lines. RASSF1A
      promoter hypermethylation was detected in 100% of SCLC, in 63% of NSCLC, in 64%
      of breast cancer lines, in 30% of primary NSCLCs, and in 49% of primary breast
      tumors but in none of the nonmalignant lung tissues. RASSF1A promoter
      hypermethylation in resected NSCLCs was associated with impaired patient survival
      (P =.046). Exogenous expression of RASSF1A in a cell line lacking expression
      decreased in vitro colony formation and in vivo tumorigenicity. CONCLUSION:
      RASSF1A is a potential tumor suppressor gene that undergoes epigenetic
      inactivation in lung and breast cancers through hypermethylation of its promoter
      region.

PMID- 11333292
TI  - p53 missense mutations in microdissected high-grade ductal carcinoma in situ of
      the breast.
AB  - BACKGROUND: To understand the role of sporadic mutations in the tumor suppressor
      gene p53 (also known as TP53) in the pathogenesis of breast cancer, it is
      important to identify at which histologic stage such mutations first occur. We
      previously showed that a p53 mutation present in invasive breast cancer was found
      in all surrounding areas of ductal carcinoma in situ (DCIS) but not in areas of
      hyperplasia or normal breast epithelium. In the present investigation, we studied
      patients with DCIS, but without invasive breast cancer, to determine the spectrum
      of DCIS types that can harbor a p53 mutation. METHODS: Formalin-fixed, paraffin
      embedded tissues from 94 patients with DCIS were evaluated histologically for the
      predominant cellular architectural pattern, degree of necrosis, and nuclear
      grade. Each specimen was also assigned an overall histologic grade (with the use
      of the Van Nuys Prognostic Index pathologic classification). Tissue specimens
      were stained immunohistochemically with an anti-p53 antibody. Positively stained
      tissue areas were analyzed for the presence of p53 mutations by single-strand
      conformation polymorphism and direct sequencing. All statistical tests were two
      sided. RESULTS: DCIS from 10 of 94 patients were found to contain p53 missense
      mutations. All 10 were of a solid or a comedo histologic pattern and contained
      cells of nuclear grade 2 or 3 (i.e., more abnormal nuclei). The frequency of p53
      missense mutations was statistically significantly different among the three
      overall histologic grade categories (zero [0%] of 49 with low-grade DCIS, one
      [4.35%] of 23 with intermediate-grade DCIS, and nine [40.9%] of 22 with high
      grade DCIS; df = 2 and P<.0001). CONCLUSION: The DCIS types in patients in this
      series are representative of clinically detected DCIS. Our finding that p53
      mutations can occur before the development of invasive breast cancer,
      particularly in DCIS of high histologic grade, has potentially important
      implications for prevention and treatment.

PMID- 11333293
TI  - Changing relationship between socioeconomic status and prostate cancer incidence.
AB  - BACKGROUND: Understanding the relationship between socioeconomic status (SES) and
      prostate cancer incidence could identify populations that should be targeted for
      intervention and prevention programs. We examined this relationship within the
      major racial/ethnic groups during the period 1972 through 1997, which spans the
      introduction of prostate-specific antigen (PSA) testing. METHODS: We used data
      from the population-based Los Angeles Cancer Surveillance Program to examine age
      adjusted prostate cancer incidence rates in five SES groups over three specific
      calendar periods by racial/ethnic subpopulation (white, black, Asian, and
      Hispanic) and by stage of disease at diagnosis. Linear regression analysis was
      used to test for trends in the age-adjusted incidence rates that were associated
      with increasing levels of SES. All P values were two-sided. RESULTS: For men
      diagnosed with prostate cancer before 1987, when the test for PSA was not widely
      available, we found no association between SES and the incidence of prostate
      cancer in any of four racial/ethnic subpopulations or between SES and the stage
      of disease at diagnosis. In contrast, among men who were diagnosed with prostate
      cancer after 1987, SES was statistically significantly and positively associated
      with prostate cancer incidence in men from all racial/ethnic subpopulations
      except Asians (P =.01 for white men, P =.001 for black men, P =.02 for Hispanic
      men, P =.06 for Asian men, and P =.01 for all men combined). Higher SES was
      statistically significantly associated with cancers of earlier stage (P =.01 for
      localized cancer and P =.00 for regional cancer) for men who were diagnosed with
      prostate cancer after 1987. CONCLUSIONS: The association between SES and prostate
      cancer incidence after 1987 may reflect more prevalent PSA screening in
      populations with higher SES due to their greater access to health care. SES
      should, therefore, be considered an important factor in interpreting variations
      and time trends in prostate cancer incidence.

PMID- 11333294
TI  - Serum hormones and the alcohol-breast cancer association in postmenopausal women.
AB  - BACKGROUND: Alcohol ingestion is associated with an increased risk of breast
      cancer in most epidemiologic studies. Results, however, are heterogeneous at
      lower levels of alcohol intake, and a biologic mechanism for the association has
      not been clearly identified. To determine whether alcohol consumption by
      postmenopausal women elevates serum levels of hormones associated with an
      increased risk of breast cancer, we performed a controlled feeding study.
      METHODS: Participants were 51 healthy postmenopausal women not using hormone
      replacement therapy. Each participant rotated through three 8-week dietary
      periods in which she consumed 15 or 30 g of alcohol per day or an alcohol-free
      placebo beverage. The order of assignment to the three alcohol levels was random.
      During the dietary periods, all food and beverages were supplied by the study,
      and energy intake was adjusted to keep body weight constant. Levels of estradiol,
      estrone, estrone sulfate, testosterone, androstenedione, progesterone,
      dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), and androstenediol were
      measured by radioimmunoassays in serum collected at the end of each dietary
      period. All statistical tests are two-sided. RESULTS: When women consumed 15 or
      30 g of alcohol per day, respectively, estrone sulfate concentrations increased
      by 7.5% (95% confidence interval [CI] = -0.3% to 15.9%; P =.06) and 10.7% (95% CI
      = 2.7% to 19.3%; P =.009) and DHEAS concentrations increased by 5.1% (95% CI =
      1.4% to 9.0%; P =.008) and 7.5% (95% CI = 3.7% to 11.5%; P<.001) relative to
      levels when women consumed placebo. None of the other hormones measured changed
      statistically significantly when women consumed alcohol. CONCLUSIONS: Results
      suggest a possible mechanism by which consumption of one or two alcoholic drinks
      per day by postmenopausal women could increase their risk of breast cancer.

PMID- 11333295
TI  - Re: Characterization of hereditary nonpolyposis colorectal cancer families from a
      population-based series of cases.

PMID- 11333296
TI  - Re: Passive smoking exposure and female breast cancer mortality.

PMID- 11333298
TI  - Re: Passive smoking exposure and female breast cancer mortality.

PMID- 11333300
TI  - A novel method to compensate for different amplification efficiencies between
      patient DNA samples in quantitative real-time PCR.
AB  - Quantification of residual disease by real-time polymerase chain reaction (PCR)
      will become a pivotal tool in the development of patient-directed therapy. In
      recent years, various protocols to quantify minimal residual disease in leukemia
      or lymphoma patients have been developed. These assays assume that PCR
      efficiencies are equal for all samples. Determining t(14;18) and albumin reaction
      efficiencies for sixteen follicular lymphoma patient samples revealed higher
      efficiencies for blood samples than for lymph node samples in general. However,
      within one sample both reactions had equivalent efficiencies. Differences in
      amplification efficiencies between patient samples (low efficiencies) and the
      calibrator in quantitative analyses result in the underestimation of residual
      disease in patient samples whereby the weakest positive patient samples are at
      highest error. Based on these findings for patient samples, the efficiency
      compensation control was developed. This control includes two reference reactions
      in a multiplex setting, specific for the beta-actin and albumin housekeeping
      genes that are present in a constant ratio within DNA templates. The difference
      in threshold cycle values for both reference reactions, ie, the Ct(2) value, is
      dependent on the amplification efficiency, and is used to compensate for
      efficiency differences between patient samples and the calibrator. The beta-actin
      reference reaction is also used to normalize for DNA input. Furthermore, the
      efficiency compensation control facilitates identification of patient samples
      that are so contaminated with PCR inhibitory compounds that different
      amplification reactions are affected to a different extent. Accurate quantitation
      of residual disease in these samples is therefore impossible with the current
      quantitative real-time PCR protocols. Identification and exclusion of these
      inadequate samples will be of utmost importance in quantitative retrospective
      studies, but even more so, in future molecular diagnostic analyses.

PMID- 11333301
TI  - Tissue microdissection and degenerate oligonucleotide primed-polymerase chain
      reaction (DOP-PCR) is an effective method to analyze genetic aberrations in
      invasive tumors.
AB  - We amplified various amounts of DNA derived from frozen SF210 and U251NCI human
      glioblastoma cells, carried out comparative genomic hybridization (CGH) using
      degenerate oligonucleotide primed-PCR (DOP-PCR) products as test probes, and
      compared results to analyses performed with probes prepared by standard nick
      translation. Next we extracted DNA from hematoxylin-eosin (HE)- and methyl green
      (MG)-stained, microdissected sections of formalin-fixed and paraffin-embedded
      U251NCI cells, amplified and labeled it by DOP-PCR, and subjected it to CGH.
      Finally, we used the same methods in multiple samples from a single human mixed
      glioma tissue. DOP-PCR products from 50 pg to 250 ng of DNA were equally
      effective in generating the same CGH profiles as the standard method. DOP-PCR
      products from microdissected pieces of MG-stained cells were effective probes for
      CGH, but HE-stained samples were not desirable. As the proportion of HE-stained
      sample increased, CGH profiles deteriorated. DOP-PCR products from microdissected
      pieces of MG-stained paraffin sections of glioma tissue produced CGH profiles
      compatible with their histological features. CGH performed with DOP-PCR products
      from microdissected paraffin blocks allows for the accurate investigation of the
      cytogenetic characteristics from invasive tumors and of cytogenetic heterogeneity
      within neoplastic tissue.

PMID- 11333302
TI  - Diagnostic impact of fluorescence in situ hybridization in the differentiation of
      hepatocellular adenoma and well-differentiated hepatocellular carcinoma.
AB  - Histopathological differentiation between hepatocellular adenoma and well
      differentiated hepatocellular carcinoma (HCC) may be a difficult task in small
      biopsies and occasionally in resected tumor specimens. Whether the analysis of
      chromosome aberrations can contribute to a more precise discrimination has not
      been analyzed systematically up to now. Therefore, fluorescence in situ
      hybridization was applied to 28 cases of adenoma and well differentiated
      carcinoma, using centromeric probes for chromosomes 1, 6, 7, 8, and X. None of 14
      adenomas revealed an aberrant count in the analyses performed. By contrast, 13/14
      carcinomas demonstrated aberrations for 2-5 chromosomes/case. Chromosome 1 was
      aberrant in 8/12 cases informative for this probe (67%), chromosomes 6 and 7 were
      aberrant in 9/14 cases (64%), chromosome 8 was aberrant in 11/14 cases (79%), and
      chromosome X in 7/14 cases (50%). Taking results for chromosomes 1 and 8
      together, 13/14 HCC revealed aberrations for at least one of these chromosomes.
      Probes for 6, 7, and X revealed no additional aberrant cases.Thus, FISH for
      chromosomes 1 and 8, extended by probes for chromosomes 6, 7 and X, represents a
      promising approach toward a more accurate differentiation between hepatocellular
      adenoma and carcinoma.

PMID- 11333303
TI  - Electronic detection of nucleic acids: a versatile platform for molecular
      diagnostics.
AB  - A novel platform for the electronic detection of nucleic acids on microarrays is
      introduced and shown to perform well as a selective detection system for
      applications in molecular diagnostics. A gold electrode in a printed circuit
      board is coated with a self-assembled monolayer (SAM) containing DNA capture
      probes. Unlabeled nucleic acid targets are immobilized on the surface of the SAM
      through sequence-specific hybridization with the DNA capture probe. A separate
      signaling probe, containing ferrocene-modified nucleotides and complementary to
      the target in the region adjoining the capture probe binding site, is held in
      close proximity to the SAM in a sandwich complex. The SAM allows electron
      transfer between the immobilized ferrocenes and the gold, while insulating the
      electrode from soluble redox species, including unbound signaling probes. Here,
      we demonstrate sequence-specific detection of amplicons after simple dilution of
      the reaction product into hybridization buffer. In addition, single nucleotide
      polymorphism discrimination is shown. A genotyping chip for the C282Y single
      nucleotide polymorphism associated with hereditary hemochromatosis is used to
      confirm the genotype of six patients' DNA. In addition, a gene expression
      monitoring chip is described that surveys five genes that are differentially
      regulated in the cellular apoptosis response. Finally, custom modification of
      individual electrodes through sequence-specific hybridization demonstrates the
      potential of this system for infectious disease diagnostics. The versatility of
      the electronic detection platform makes it suitable for multiple applications in
      diagnostics and pharmacogenetics.

PMID- 11333304
TI  - Characterization of an isoform of rice starch branching enzyme, RBE4, in
      developing seeds.
AB  - cDNA clones encoding an isoform of starch branching enzyme, RBE4, have been
      identified from a developing rice seed cDNA library, using a synthetic
      oligonucleotide probe corresponding to the N-terminal amino acid sequence of
      RBE4. The cDNA-derived amino acid sequence indicated that RBE4 is initially
      produced as a precursor protein of 841 amino acids, including a 53-residue
      transit peptide at the N-terminus. The mature form of RBE4 shared a high degree
      of sequence identity (80%) with mature RBE3, and possessed an N-terminal extra
      sequence, as found in RBE3. Northern blot analysis demonstrated that the RBE4
      gene is expressed in both leaves and developing seeds. The RBE4 gene was
      distinguished from the RBE1 and RBE3 genes by expression at the earlier stages of
      seed development. To examine enzymatic functions of RBE4, recombinant proteins
      were produced in Escherichia coli cells, and purified by two chromatographic
      separations. The branched alpha-glucans produced by the recombinant enzymes from
      potato amylose revealed the different patterns of oligosaccharide chain transfer.
      The peak of major branches of the products by RBE3 or RBE4 was 6 glucose units,
      whereas the peaks of major branches of the products by RBE1 were 6 and 11 glucose
      units. The similar property between RBE3 and RBE4 is supported by high similarity
      of the amino acid sequences between them.

PMID- 11333305
TI  - Mechanosensitive Ca2+ release from intracellular stores in Nitella flexilis.
AB  - We found previously that the cytoplasmic drop isolated from internodal cells of
      Nitella flexilis releases Ca2+ in response to hypotonic treatment and named the
      phenomenon hydration-induced Ca2+ release (HICR). The HICR is assumed to be a
      result of activation of Ca2+ permeable channels in the membrane of Ca2+ stores in
      a stretch-activated manner. To prove this idea, mechanical stimulus was applied
      to the drop by means of shooting isotonic/hypnotic medium or silicon oil into the
      drop, or compressing the drop. All these mechanical stimuli induced a rapid
      increase in the Ca2+ concentration of the drop. The chloroplast fraction isolated
      from the cytoplasmic drop released Ca2+ on compression, while the chloroplast
      free cytoplasm did not. In Chara corallina, the cytoplasmic drop, which shows a
      very weak HICR, also responded weakly to the mechanical stimulus, but the
      chloroplast fraction was inert. When chloroplasts from Chara were added to the
      chloroplast-free cytoplasm of N. flexilis, the cytoplasm recovered the
      mechanoresponse. Starch grains were as effective as chloroplasts. The data
      indicate that Ca2+ permeable channels in the membrane of Ca2+ stores in N.
      flexilis are really mechano-sensitive.

PMID- 11333306
TI  - Electrical perception of "death message" in Chara: involvement of turgor
      pressure.
AB  - Plants show various defense responses upon wounding. Surviving cells must
      perceive a "death message" from killed cells in order to start the signal
      processing that results in defense responses. The initial step in perception of
      the death message by a surviving cell was studied by taking advantage of the
      filamentous morphology of characean algae. A specimen comprising two adjoining
      internodal cells was prepared. One cell (the victim cell) was killed by cutting
      and any changes in the membrane potential of the neighboring cell (the receptor
      cell) were analyzed. Upon cutting the victim cell, at least one of three kinds of
      response were induced in the receptor cell: (1) slow depolarization lasting more
      than 10 min, (2) action potentials and (3) small spikes. The first of these
      response types, slow depolarization, was ubiquitous and is the focus of the
      present study. Two cell properties were essential for generation of this
      depolarization. (1) Presence of high cell turgor pressure was necessary. (2) The
      depolarization was generated only at the nodal end of the receptor cell, not at
      the flank. I concluded that the death message from the killed cell contains the
      information that turgor pressure has been lost. The mechanism by which this is
      translated into the slow depolarization of the receptor cell was discussed.

PMID- 11333307
TI  - Expression of two HOOKLESS genes in peas (Pisum sativum L.).
AB  - The apical hook of dark-grown dicotyledonous plants results from asymmetric
      growth of its inner and outer sides. It is a protective structure that prevents
      damage to the shoot apical meristem and the young leaves as the seedling pushes
      through the soil. Two phytohormones, ethylene and auxin, are thought to be
      involved in regulating apical hook formation. HOOKLESS1 (HLS1) of Arabidopsis was
      recognized as an ethylene-response gene whose product is required for hook
      formation. We cloned two cDNAs from peas, Ps-HLS1 and Ps-HLS2, whose products are
      functional homologs of HLS1. Both Ps-HLS1 and Ps-HLS2 complement the hls1
      mutation in Arabidopsis. Expression of Ps-HLS1 is enhanced by ethylene and by
      IAA. Because the effect of ethylene is counteracted by 2,5-norbornadiene, an
      inhibitor of ethylene action, it appears that the primary factor in apical hook
      formation in peas is ethylene.

PMID- 11333308
TI  - Physiological significance of the regulation of photosystem stoichiometry upon
      high light acclimation of Synechocystis sp. PCC 6803.
AB  - We characterized the photosynthetic properties of the pmgA mutant of
      Synechocystis PCC 6803, which cannot change its photosystem stoichiometry under a
      high-light condition (200 micromol x m(-2) x s(-1)), in order to clarify the
      physiological significance of the regulation of photosystem stoichiometry. We
      found that (1) PSII activity was inhibited more in wild-type cells on the first
      day under the high-light conditions than in mutant cells. (2) The growth of the
      mutants following the initial imposition of high light was faster than that of
      wild-type cells. (3) However, growth was severely inhibited in the mutants after
      the third day of exposure to high light. (4) The growth inhibition in the mutants
      under the extended high-light conditions was reversed by the addition of
      sublethal concentrations of 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU), which
      seemed to mimic photoinhibition of PSII. These results suggest that the main role
      of adjusting the photosystem stoichiometry with respect to light intensity is not
      to maintain efficient photosynthesis, but to down regulate electron transfer.
      Failure to down regulate electron flow leads to cell death under prolonged
      exposure to high light in this cyanobacterium.

PMID- 11333309
TI  - The molecular characterization and in situ expression pattern of pea SCARECROW
      gene.
AB  - Certain mutants of shoot gravitropism were reported to be ascribed to the SCR and
      SHR loci in Arabidopsis thaliana. The SCR gene was known to regulate the
      development of endodermis cells that are responsible for sensing gravity in a
      shoot. With the aim of elucidating the molecular mechanism for gravitropic
      responses in pea seedlings, we have isolated a putative pea SCR ortholog from a
      shoot cDNA library. Analyses of the cDNA clones revealed the structure of a full
      length ORF coding for 819 amino acid residues. A remarkable feature of pea SCR
      protein was the presence of asparagine stretches at the N-terminal
      transcriptional activation domain, which was distinct from the occurrence of
      glutamine or alanine stretches in the Arabidopsis or maize SCR. A Northern blot
      analysis revealed a single 3.2-kb pea SCR transcript in addition to a closely
      related 2.5-kb transcript. Our in situ hybridization data indicated that pea SCR
      mRNA accumulated in the shoot apical meristem, leaf primordia and a root single
      cell layer corresponding to the endodermis. The expression patterns were similar
      to those reported for A. thaliana and Zea mays, suggesting that SCR may be
      functionally conserved among plants and involved in the differentiation of the
      endodermis.

PMID- 11333310
TI  - Involvement of cortical microtubules in plastic extension regulated by
      gibberellin in Lemna minor root.
AB  - We aimed to analyze the rheological characteristics during elongation of the root
      segments in Lemna minor. The elastic component of segment elongation (EC)
      increased for the first 6 h, and then almost stopped. However, the plastic
      component of the segment elongation (PC) began to rapidly increase from 6 h
      onwards. Uniconazole-P, a gibberellin biosynthesis inhibitor, inhibited the total
      elongation of root segments (TE), and this inhibition was mainly caused by
      suppression of the rapid increase in the PC after 6 h. Concomitant with this
      inhibition, the cortical microtubule (CMT) array within root epidermal cells
      became disorganized in the presence of uniconazole-P from 6 h onwards. Adding GA3
      abolished the inhibition of TE by uniconazole-P treatment, and this recovery was
      caused not by the increase in the EC but by an increase in the PC. Furthermore,
      the CMT arrays also recovered their characteristic organization in the presence
      of GA3. These findings suggest that endogenous gibberellin accelerates TE by
      activating the PC via control of CMT arrays. This conclusion is also supported by
      rheological analysis where propyzamide was used to disrupt microtubules. We
      suggest that endogenous gibberellin controls the PC via its influence over the
      transverse arrangement of CMTs.

PMID- 11333312
TI  - The establishment of conditions to efficiently screen photosynthesis-deficient
      mutants of Synechocystis sp. PCC 6803 by nitrofurantoin treatment.
AB  - A method based on the susceptibility of photosynthetic organisms to
      nitrofurantoin under illumination was established to screen mutants of
      Synechocystis sp. PCC 6803 deficient in the function of photosystem II, which
      were created by random PCR mutagenesis targeted to the psbAII gene coding for the
      D1 protein of the photosystem II reaction center. In this method, cyanobacterial
      colonies on a nitrocellulose membrane on a BG11 agar plate were treated with
      nitrofurantoin at 1.0 mM under white light at 40 microE x m(-2 ) x s(-1) for 2 h,
      and then kept under normal conditions without nitrofurantoin so that surviving
      cells could grow. This method was also shown to be useful for screening mutants
      deficient in the function of photosystem I.

PMID- 11333311
TI  - A Brassica oleracea gene expressed in a variety-specific manner may encode a
      novel plant transmembrane receptor.
AB  - The species Brassica oleracea includes several agricultural varieties
      characterized by the proliferation of different types of meristems. Using a
      combination of subtractive hybridization and PCR (polymerase chain reaction)
      techniques we have identified several genes which are expressed in the
      reproductive meristems of the cauliflower curd (B. oleracea var. botrytis) but
      not in the vegetative meristems of Brussels sprouts (B. oleracea var. gemmifera)
      axillary buds. One of the cloned genes, termed CCE1 (CAULIFLOWER CURD EXPRESSION
      1) shows specific expression in the botrytis variety. Preferential expression
      takes place in this variety in the meristems of the curd and in the stem
      throughout the vegetative and reproductive stages of plant growth. CCE1
      transcripts are not detected in any of the organs of other B. oleracea varieties
      analyzed. Based on the nucleotide sequence of a cDNA encompassing the complete
      coding region, we predict that this gene encodes a transmembrane protein, with
      three transmembrane domains. The deduced amino acid sequence includes motifs
      conserved in G-protein-coupled receptors (GPCRs) from yeast and animal species.
      Our results suggest that the cloned gene encodes a protein belonging to a new, so
      far unidentified, family of transmembrane receptors in plants. The expression
      pattern of the gene suggests that the receptor may be involved in the control of
      meristem development/arrest that takes place in cauliflower.

PMID- 11333313
TI  - Engineering variegated floral patterns in tobacco plants using the Arabidopsis
      transposable element Tag1.
AB  - Variegated flower phenotypes were generated using the Arabidopsis transposon Tag1
      and the maize R regulatory gene. Tag1 was inserted between the CaMV 35S promoter
      and the maize R gene and transformed into tobacco plants. In half of the
      transgenic plants, variegated flower patterns were observed. Each line had a
      different pattern, with varying intensities with three lines showing only tiny
      sectors indicative of late excision and one showing large sectors indicative of
      earlier excision.

PMID- 11333314
TI  - Analysis of the phosphorylation level in guard-cell plasma membrane H+-ATPase in
      response to fusicoccin.
AB  - A fungal phytotoxin fusicoccin (FC) causes irreversible opening of stomata by
      activation of the plasma membrane H+-ATPase in guard cells. However, the
      mechanism by which FC activates the H+-ATPase is not fully understood with
      respect to the event of phosphorylation. In this study, we provide quantitative
      evidence that FC-dependent activation of H+-ATPase requires the phosphorylation
      of the C-terminus, and that FC maintains the activated state by preventing the
      dephosphorylation. The plasma membrane H+-ATPase in guard cells was
      phosphorylated on serine and threonine residues in the C-termini of both VHA1 and
      VHA2 by FC, and the phosphorylation level paralleled the rates of H+-pumping and
      ATP hydrolysis. An endogenous 14-3-3 protein was co-precipitated with the H+
      ATPase, and the amount of 14-3-3 protein was proportional to the phosphorylation
      level of H+-ATPASE: The recombinant 14-3-3 protein bound to the C-terminus only
      when it was phosphorylated, even in the presence of FC. The phosphorylated C
      terminus was dephosphorylated by alkaline phosphatase, and the dephosphorylation
      was completely prevented when the C-terminus had been incubated with both FC and
      14-3-3 protein. The results suggest that FC activates the H+-ATPase by
      accumulating the complex of phosphorylated H+-ATPase and 14-3-3 protein through
      inhibition of the dephosphorylation in guard cells.

PMID- 11333315
TI  - Characterization of ascorbate peroxidases from unicellular red alga Galdieria
      partita.
AB  - Galdieria partita, a unicellular red alga isolated from acidic hot springs and
      tolerant to sulfur dioxide, has at least two ascorbate peroxidase (APX) isozymes.
      This was the first report to demonstrate that two isozymes of APX are found in
      algal cells. Two isozymes were separated from each other at the hydrophobic
      chromatography step of purification and named APX-A and APX-B after the elution
      order in the chromatography. APX-B accounted for 85% of the total activity. Both
      isozymes were purified. APXs from Galdieria were monomers whose molecular weights
      were about 28,000, similar to stromal APX of higher plants. APX-A cross-reacted
      with monoclonal antibody raised against APX of Euglena gracilis in
      immunoblotting, but APX-B did not, although the antibody can recognize all other
      APXs tested. The amino-terminal sequences of APX-A and -B from Galdieria had some
      homology with each other but little homology with those from other sources. Their
      Km values for ascorbate and hydrogen peroxide were comparable with those of APX
      from higher plants. Unlike the green algal enzymes, the donor specificities of
      Galdieria APXs were as high as those of plant chloroplastic APX. On the contrary,
      these APXs reduced tertiary-butyl hydroperoxide as an electron acceptor as APXs
      from Euglena and freshwater Chlamydomonas do. The inhibition of APX-A and -B by
      cyanide and azide, and characteristics of their light absorbance spectra
      indicated that they were heme peroxidases.

PMID- 11333316
TI  - In vivo phosphorylation of phosphoenolpyruvate carboxylase in Egeria densa, a
      submersed aquatic species.
AB  - In vivo phosphorylation of PEPC in Egeria densa was studied using plants at high
      temperature and in light, and plants kept at low temperature and in light. The
      isoform induced by high temperature and light was more phosphorylated in the
      light. Changes in kinetic and regulatory properties correlated with changes in
      the phosphorylation state of PEPC.

PMID- 11333317
TI  - Effect of methyl jasmonate on harpin-induced hypersensitive cell death,
      generation of hydrogen peroxide and expression of PAL mRNA in tobacco suspension
      cultured BY-2 cells.
AB  - Methyl jasmonate inhibited the harpin-induced defense responses such as cell
      death, H2O2 generation and gene expression encoding phenylalanine ammonia-lyase
      in tobacco suspension cultured BY-2 cells. These results suggest that MeJA may
      act as an endogenous suppressor for plant defense response including
      hypersensitive reaction.

PMID- 11333318
TI  - Penetrating keratoplasty in eyes treated with conjunctival flaps.
AB  - PURPOSE: To analyze the results of corneal transplants in severely inflamed eyes
      previously treated with conjunctival flaps. METHODS: In the period 1984-1996,
      seven homoplastic penetrating keratoplasties (PKs) and one rotating
      autokeratoplasty were performed on a series of 47 eyes of 46 patients treated
      with partial or total conjunctival flaps. Two of these PKs were combined with an
      extracapsular cataract extraction, and the rotating autograft was combined with
      an extracapsular cataract extraction and intraocular lens implantation. Patient
      ages ranged between 25 and 52 years (three men and five women), and the follow-up
      period was 3 to 15 years. The recipient corneal buttons were studied
      histopathologically. RESULTS: The eight graftings remained transparent; two cases
      developed glaucoma that was controlled with medication, and one had a rejection
      episode, which disappeared with medical treatment. All patients reached a
      postoperative vision between 20/70 and 20/30. CONCLUSION: Therapeutic
      conjunctival flaps improve the conditions of the recipient bed for transplant in
      severely inflamed eyes.

PMID- 11333319
TI  - Outcome of Corneal transplantation rejection.
AB  - PURPOSE: To identify predictive factors for reversibility of corneal graft
      rejection. METHODS: The study design was a prospective cohort study. Among 440
      consecutive penetrating keratoplasties performed at our institution, 79 grafts
      from 79 patients who developed signs of transplant rejection were included.
      Donor, recipient, surgical, and rejection variables were studied, at both
      univariate and multivariate levels. RESULTS: The rate of reversibility was 51%
      (40/79). The average postoperative time of rejection was 10.5 +/- 9.3 months, and
      the average time of visual acuity recovery in patients with reversible rejection
      was 2.4 +/- 2.3 months. In logistic regression, only two variables significantly
      influenced the rate of reversibility. The preoperative diagnosis (p = 0.04)
      influenced the rate of rejection reversibility; patients with bullous keratopathy
      or regraft were more likely to experience irreversible rejection than patients
      with keratoconus or Fuchs' dystrophy. The average graft thickness at the time of
      rejection diagnosis was 774 +/- 129 microm in patients with irreversible
      rejection and 681 +/- 118 microm in patients with reversible rejection (p =
      0.001). CONCLUSION: Rejection was reversible in half of the cases. Rejection was
      more likely to be irreversible in patients with marked increase in graft
      thickness and in patients transplanted for bullous keratopathy or graft failure.
      Donor variables did not influence rejection reversibility.

PMID- 11333320
TI  - Amniotic membrane transplantation after the primary surgical management of band
      keratopathy.
AB  - PURPOSE: To determine the safety and efficacy of amniotic membrane
      transplantation to restore and maintain a stable corneal epithelium and reduce
      ocular surface pain after surgical removal of band keratopathy arising from
      ocular causes. METHODS: Fifteen patients (16 eyes) from two centers with band
      keratopathy secondary to ocular causes underwent amniotic membrane
      transplantation as a graft after surgical removal of calcific deposits with or
      without the use of ethylenediaminetetraacetic acid. In a prospective,
      consecutive, uncontrolled case series, the rate of corneal epithelialization and
      resultant surface stability were recorded over a mean follow-up period of 14.6
      months. RESULTS: Pain from ocular surface instability was the presenting
      complaint in 14 of 15 (93.3%) patients and resolved in all cases after the
      procedure even for those who experienced a recurrence of the calcific deposit.
      Fifteen of 16 eyes (93.7%) achieved epithelialization with a mean time to
      epithelial healing of 15.2 days. The only eye that failed to heal was
      subsequently diagnosed with total limbal stem cell deficiency. Visual acuity
      improved in five of nine (44%) sighted eyes and remained unchanged in four of
      nine (56%). No patient experienced any major surgical or medical complication
      after the procedure. CONCLUSION: Amniotic membrane transplantation represents a
      safe and effective method to restore a stable corneal epithelium in eyes after
      primary surgical removal of band keratopathy arising from ocular causes.

PMID- 11333321
TI  - The detection of bacteria and bacterial biofilms in punctal plug holes.
AB  - PURPOSE: An investigation into bacterial biofilm formation on and in punctal
      plugs. METHODS: The study involved 21 patients with severe dry eye whose puncta
      were occluded by the use of punctal plugs. Of these, 15 had Sjogren's syndrome, 3
      had non-Sjogren's syndrome, 2 had Stevens-Johnson syndrome, and 1 had graft
      versus-host disease. From 17 of the 21 subjects, 18 samples of material were
      extracted from the holes of the punctal plugs (16 unilateral and 1 bilateral) and
      were subjected to enrichment culture. Nineteen punctal plugs were removed and
      processed for electron microscopy: 15 by scanning electron microscopy, and 4 by
      transmission electron microscopy. RESULTS: Positive cultures were found in 8 of
      18 (44%) samples of the material extracted from the holes of punctal plugs. In
      six of these eight cases (75%) the cultured bacterial species was Staphylococcus
      epidermidis, whereas in the other two cases (25%) it was S. aureus. In 8 of the
      15 punctal plugs examined by scanning electron microscopy and in the material
      extracted from 1 plug that was examined by transmission electron microscopy,
      there was clear evidence of bacterial colonization. CONCLUSION: Careful
      observation of patients with punctal plugs is important. If material accumulates
      in or on a punctal plug, it may contain bacteria and may form a bacterial
      biofilm. In these cases, replacement of the plug, clearing of the hole, or an
      alternative treatment should be considered.

PMID- 11333322
TI  - Astigmatism associated with Fuchs' heterochromic iridocyclitis.
AB  - PURPOSE: To determine whether there is inherent corneal astigmatism in patients
      with Fuchs' heterochromic iridocyclitis (FHI). PATIENTS AND METHODS: A case
      controlled study of 48 patients with unilateral FHI was conducted. These patients
      had no history of previous surgery or previous diagnosis of glaucoma or cataract.
      The controls were the fellow eyes of the patients, and the cases were the FHI
      eyes. All eyes were refracted, and the results were analyzed with descriptive and
      parametric statistics. RESULTS: Twenty-one women and 27 men were studied. The
      mean age was 39.5 years. The mean keratometric value for the astigmatism in the
      FHI eye was 2.2 diopters (D) (standard deviation +/-1.19) and 0.96 D (+/- 0.64)
      in the controls (p= 0.000). Refractive astigmatism was 1.44 D (+/-1.45) in FHI
      eyes and 0.38 D (+/-0.62) in the controls (p= 0.000). CONCLUSIONS: Patients with
      unilateral FHI have inherent corneal astigmatism in the disease eye.

PMID- 11333323
TI  - In vivo confocal microscopy of patients with amiodarone-induced keratopathy.
AB  - PURPOSE: To describe the corneal findings in patients with amiodarone-induced
      keratopathy by means of in vivo confocal microscopy. METHODS: Twenty-two eyes of
      11 patients (eight men and three women) receiving amiodarone therapy and 20 eyes
      of 10 healthy sex-and age-matched control subjects were selected for confocal
      microscopic examination. The patients were examined by use of a scanning slit
      corneal confocal microscope (Confoscan 2.0). Five complete scans of the entire
      cornea were performed for each eye with a total examination time of less than 5
      minutes. RESULTS: All patients receiving amiodarone showed the presence of high
      reflective, bright intracellular inclusions in the epithelial layers. These
      findings were more evident within the basal cell layers. In the eyes with
      advanced keratopathy (stages 2 and 3), bright microdots were detectable within
      the anterior and posterior stroma and on the endothelial cell layer. In the
      anterior stroma, the keratocyte density in the treated group was reduced compared
      with values of the control group (p < 0.001), and a markedly irregular aspect of
      the stromal nerve fibers was found. The main characteristic of this nerve
      irregularity was represented by the clew-shaped appearance of the nerve trunks.
      CONCLUSION: Detailed examination of corneal structure by confocal microscopy
      shows that amiodarone keratopathy in long-term treated patients presents some
      findings that are consistent with higher toxicity than was expected and that
      involve the deep corneal layers.

PMID- 11333324
TI  - Morphology of corneal nerves using confocal microscopy.
AB  - PURPOSE: The aim of the current study was to evaluate the distribution and
      morphology of corneal nerves as seen by means of white light confocal microscopy.
      METHODS: This study analyzed images of corneal nerves that were obtained using
      the Tomey Confoscan slit scanning confocal microscope (40x/0.75 objective lens).
      The images were classified according to their location within the cornea. The
      objective and subjective evaluation of the images involved measuring, grading, or
      judging a number of parameters from both individual pictures and from each single
      nerve fiber within any image. RESULTS: The in vivo observations made in this work
      are in agreement with those of previous histologic studies. The general scheme of
      corneal innervation is described as originating from thick and straight stromal
      nerve trunks that extend lateral and anteriorly and give rise to plexiform
      arrangements of progressively thinner nerve fibers at several levels within the
      stroma. From there, nerve fibers perforate Bowman's layer and eventually form a
      dense neural plexus just beneath the basal epithelial cell layer, which is
      characterized by tortuous and thin beaded nerve fibers interconnected by numerous
      nerve elements; nerve fibers from this plexus are known to be responsible for the
      innervation of the epithelium. CONCLUSION: This study provides convincing
      evidence of the suitability of confocal microscopy to image corneal nerves, the
      only drawback being the limited resolution in terms of the differentiation of the
      ultrastructure of nerve bundles.

PMID- 11333325
TI  - Laser in situ keratomileusis versus photorefractive keratectomy in the correction
      of myopic astigmatism.
AB  - PURPOSE: To evaluate retrospectively the effectiveness of astigmatism correction
      in eyes treated with laser in situ keratomileusis (LASIK) and photorefractive
      keratectomy (PRK). METHODS: Patients with low to moderate myopia with astigmatism
      ranging from +0.25 to +4.50 diopters were included in the study. PRK was
      performed on 62 eyes and LASIK on 70 eyes. Six-month data were analyzed with
      regard to astigmatism power, astigmatism axis, spherical equivalent, uncorrected
      visual acuity, vector astigmatism change, and topographic corneal regularity.
      RESULTS: Mean astigmatism magnitude change was 0.54 +/- 0.76 in PRK-treated eyes
      and 0.60 +/- 0.67 in LASIK-treated eyes (61% versus 64% change, respectively, p =
      0.61) at 6 months after surgery. Mean spherical correction change was -2.79 +/-
      1.51 for PRK and -2.90 +/- 1.03 for LASIK (p = 0.63). Mean spherical equivalent
      change was -2.5 +/- 1.57 for PRK and -2.6 +/- 1.23 for LASIK (p = 0.73). Mean
      change in astigmatism axis was 20.8 +/- 73.1 for PRK and 33.8 +/- 81.7 for LASIK
      (p = 0.34). Mean change in uncorrected visual acuity (LogMar) was 0.84 +/- 0.26
      for PRK and 0.89 +/- 0.23 for LASIK (p = 0.21). Mean vector-corrected astigmatism
      change was 0.88 +/- 0.66 for PRK and 0.95 +/- 0.59 for LASIK (p = 0.51). Mean
      vector-corrected astigmatism axis for PRK was 86.9 +/- 59 degrees and for LASIK
      83.8 +/- -47.6 degrees (p = 0.75). CONCLUSION: There was no significant
      difference in astigmatism correction between PRK and LASIK at 6 months after
      surgery.

PMID- 11333326
TI  - Hyperopic laser in situ keratomileusis: primary and secondary treatments are safe
      and effective.
AB  - PURPOSE: To retrospectively analyze the safety and efficacy of hyperopic laser in
      situ keratomileusis (LASIK) treatment of eyes with primary hyperopia and
      consecutive hyperopia after initial myopic treatment. METHODS: Thirty-two eyes of
      19 patients with primary hyperopia (group 1) and 37 eyes of 26 patients with
      consecutive hyperopia after initial myopic LASIK overcorrection (group 2) that
      had LASIK for hyperopia with the Hansatome microkeratome and VISX S2 Smoothscan
      excimer laser with 6 months' follow-up after surgery were analyzed. Uncorrected
      visual acuity, best spectacle-corrected visual acuity, fogged manifest
      refraction, and corneal topography with corneal irregularity measurement (CIM)
      were evaluated 1 month, 3 months, and 6 months after surgery. RESULTS: In group
      1, the mean preoperative cycloplegic spherical equivalent was +4.0 +/- 4.5
      diopters (D) (range, +1.5 to + 8.75 D) and the 6-month postoperative cycloplegic
      spherical equivalent was +0.26 +/- 1.74 D (range, -3.00 to +2.75 D). Fifty-three
      percent of eyes (n= 17) in group 1 were within 1 D of emmetropia. Sixty-six
      percent of eyes (n= 21) had uncorrected visual acuity of at least 20/40. Three
      eyes (9%) lost two lines of best spectacle-corrected visual acuity. Changes in
      uncorrected visual acuity, best spectacle-corrected visual acuity, spherical
      equivalent, and the CIM topographic index 6 months after surgery were
      statistically significant compared with the preoperative values. In group 2, the
      mean preoperative cycloplegic spherical equivalent was +1.58 +/- 0.35 D (range,
      +0.125 to +2.75 D), and the mean postoperative cycloplegic spherical equivalent
      was -0.48 +/- 0.46 (range, -2.75 to +0.38 D). Eighty-six percent of eyes (n= 32)
      were within 1 D of emmetropia. Eighty-four percent of eyes (n= 31) in group 2 had
      uncorrected visual acuity of at least 20/40. One eye (2.7%) lost two lines of
      best spectacle-corrected visual acuity. Complications included an epithelial nest
      that resolved 3 months after surgery in one eye in group 2. CONCLUSIONS: LASIK is
      a relatively safe treatment of primary hyperopia and hyperopia resulting from
      overcorrection after initial LASIK treatment of myopia (consecutive hyperopia).
      Patients with high hyperopia (>5 D) are at risk for loss of two lines of best
      spectacle-corrected visual acuity. A reduction in the level of attempted
      correction appears to be necessary in the treatment of consecutive hyperopia.

PMID- 11333327
TI  - Corneal hydration affects ablation during laser in situ keratomileusis surgery.
AB  - BACKGROUND: Studies in animal eyes indicate that the level of corneal hydration
      affects the ablation rate of laser surgery; the greater the hydration is, the
      less the ablation for a given laser pulse. Our study is an assessment in human
      eyes comparing the effects on ablation by blotting the corneal stromal surface
      under a corneal flap created for laser in situ keratomileusis (LASIK) procedures
      between sets of excimer laser pulses, with ablation depth in eyes not blotted
      between sets of laser pulses. METHODS: We modified the surgical technique for
      LASIK procedures to assess the effects of the level of hydration on excimer laser
      ablation depth per pulse. In group 1, 40 eyes underwent LASIK surgery without any
      modification. Group 2 was composed of 36 eyes having LASIK procedures, but the
      corneal surfaces were kept relatively dry by blotting of the stromal surface
      between sets of laser pulses. RESULTS: Six months after surgery, the mean
      spherical equivalent refractive change was from -8.38 diopters (D) to -1.44 D in
      group 1 and from -7.93 D to -0.09 D in group 2. For predictability, the deviation
      from the target refraction after surgery was assessed. Thirty-three percent (13
      of 40) in group 1 and 25% (9 of 36) in group 2 were within +/-0.5 D. Forty-eight
      percent (19 of 40) in group 1 and 50% (18 of 36) in group 2 were within +/-1 D.
      Six months after surgery, 80% or more in both groups were within +/-2 D. There
      was myopic regression in all patients. Three months after surgery, regression
      averaged -0.71 D in group 1 and -1.15 D in group 2. CONCLUSIONS: Corneal
      hydration levels affect the efficiency of laser ablation in LASIK procedures.
      With less hydrated corneas, ablation effects were greater than for corneas not
      blotted during the procedure, but these patients appear to undergo greater myopic
      regression.

PMID- 11333328
TI  - Indications for lamellar keratoplasty in India.
AB  - PURPOSE: To study the indications for lamellar keratoplasty (LK) in a tertiary
      eye care hospital in northern India. METHODS: A retrospective analysis of 71 eyes
      that had undergone LK between January 1995 and December 1999 was performed. The
      parameters evaluated included demographic data, the diagnosis at admission, the
      laterality of involvement, and the graft size. RESULTS: The mean age of the
      patients was 31 +/- 21.8 years (range, 1-73 years). Forty-one male patients and
      30 female patients underwent LK. Thirty-three patients (47%) lived in rural
      areas, and 38 patients (53%) were urban dwellers. LK was performed for optical
      indications in 63 eyes (88.7%), for tectonic purposes in six eyes (8.4%), and for
      therapeutic purposes in two eyes (2.8%). Chemical injuries (18%) were the most
      common indication for LK and were followed by trachomatous keratopathy (14%) and
      dermoids (14%). CONCLUSION: Chemical injuries, trachomatous keratopathy, and
      dermoids constitute the major indications for LK in India.

PMID- 11333329
TI  - Identifying the origin of single corneal cells by DNA fingerprinting: part I-
      implications for corneal limbal allografting.
AB  - PURPOSE: To demonstrate that the combination of impression cytology and single
      cell DNA fingerprinting represents a powerful tool that is suitable for detecting
      transplanted cells after corneal limbal allografting. METHODS: Fifty single cells
      were obtained by corneal impression cytology from 12 patients undergoing cataract
      surgery. Individual cells were isolated from samples by micromanipulation.
      Polymerase chain reaction and short tandem repeat profiling was used to obtain
      forensic standard "DNA fingerprints" from single cells. Blood samples taken at
      the time of impression cytology provided control "fingerprints." RESULTS:
      Informative DNA fingerprints were obtained from all corneal samples and 66% (33
      of 50 cells) of isolated single cells. Of all fingerprints obtained, most (91%,
      30 of 33 fingerprints) corneal fingerprints matched corresponding blood sample
      fingerprints. At least one corneal fingerprint matched the corresponding blood
      sample fingerprint in 83% (10 of 12 patients) of the patients in the study.
      CONCLUSIONS: This extremely specific single cell DNA fingerprinting system
      permits accurate identification of individual corneal epithelial cells, allowing
      very reliable determination of their origin, which will enable host and donor
      cells to be distinguished from each other after keratolimbal allografting
      procedures, even if the host and donor are the same sex or siblings. These DNA
      fingerprinting methods allow assessment of quality and quantity of donor cell
      survival, as well as survival time. The extreme sensitivity and accuracy of the
      technique means that should contamination occur, it would be identified, thus
      ensuring meaningful results.

PMID- 11333330
TI  - Identifying the origin of single corneal cells by DNA fingerprinting: part II--
      application to limbal allografting.
AB  - PURPOSE: Successful limbal allotransplantation allows regression of limbal stem
      cell deficiency features. Transplant survival is presumed if clinical improvement
      occurs. However, positive proof of surviving transplanted stem cells remains
      difficult. This follow-up study attempted to prove donor cell survival 5 years
      after limbal stem cell allograft in one woman with aniridia. METHODS: Impression
      cytology and single-cell DNA fingerprinting were used to investigate a previously
      studied patient. Corneal epithelial cells were harvested from five sites and
      isolated by micromanipulation. Polymerase chain reaction and short tandem repeat
      profiling were used to obtain forensic standard "DNA fingerprints" from single
      cells. (The technique is described in the preceding article, Part I.) Blood
      samples yielded host and donor DNA for comparison. Negative controls were
      performed for impression cytology and polymerase chain reaction. Simultaneous
      micro-scrape samples were also taken. RESULTS: Impression cytology samples
      permitted informative DNA fingerprints from all corneal sites and represented 76%
      (23/30) of tested cells. Fifty percent (15/30) of the fingerprints were
      "specific" but 83% (19/23) matched the host DNA fingerprint. The remaining 17%
      (4/23) represented contamination from various sources. Specific fingerprints were
      obtained in 55% (10/18) of the cells from micro-scrape samples. All samples
      giving sufficient information matched the host DNA fingerprint. All tested blood
      samples gave specific fingerprints. None of the sampled corneal cells gave a
      donor DNA fingerprint. CONCLUSIONS: In a single patient, no detectable long-term
      donor cell survival exists at 5 years. Positive identification would have
      provided unequivocal proof of donor cell survival. This technique gives useful
      information even if contamination occurs.

PMID- 11333331
TI  - Antiinflammatory effects of amniotic membrane transplantation in ocular surface
      disorders.
AB  - PURPOSE: To determine whether the sequestration of inflammatory cells plays a
      role in the antiinflammatory effects of amniotic membrane transplantation to the
      ocular surface. METHODS: Amniotic membrane grafts were prepared from placental
      tissue procured from mothers undergoing planned Cesarean sections. A detailed
      explanation was given to all donors, and a written consent was obtained before
      processing. Amniotic membrane tissue was dissected into 3- x 3-cm segments,
      rinsed in phosphate buffered saline, and stored in dimethyl sulfoxide solutions
      at -80 degrees C until use. In a clinical series, amniotic membrane patches of
      the ocular surface were performed in 20 eyes of 20 patients with persistent
      corneal epithelial defects, or as a prophylactic measure after corneal limbal
      transplantation. Amniotic membrane patches were harvested after a 1-week
      observation period and were subjected to histopathologic examinations by
      hematoxylin and eosin staining. Inflammatory cells trapped within the amniotic
      membrane were labeled by immunocytochemistry using anti-CD14, CD4, CD8, and CD20
      antibodies. TUNEL (TdT-mediated dUTP nick end labeling) staining was done to
      observe cells undergoing apoptosis. The T cell line Molt 4 was co-cultured with
      amniotic membrane in vitro to observe adhesion of T cells to amniotic membrane.
      RESULTS: Various degrees of inflammatory cell infiltration were observed in all
      clinical samples of amniotic membrane patches. Most of the inflammatory cells
      stained positively with anti-CD14 antibodies, indicating that these cells were of
      monocyte/macrophage lineage. Subsets of T cells included both CD4(+) and CD8(+)
      cells, whereas CD20(+) cells were sparse. TUNEL assays revealed that trapped
      inflammatory cells exhibited characteristics of cells undergoing apoptosis. Molt
      4 invaded within amniotic membrane in an in vitro assay, which was not inhibited
      by blocking antibodies to beta1 and beta2 integrins. CONCLUSION: Amniotic
      membrane attracts and traps inflammatory cells infiltrating the ocular surface,
      which may explain some of the antiinflammatory properties of the fetal tissue.

PMID- 11333332
TI  - Reconstruction of ocular surface with heterologous limbal epithelium and amniotic
      membrane in a rabbit model.
AB  - PURPOSE: To report in vivo reconstruction of the ocular surface using amniotic
      membrane and heterologous transplants of epithelial limbal cells in rabbits with
      chemical burns. METHODS: After severe damage to the ocular surface with n
      heptanol and keratectomy, 15 rabbits developed total limbal deficiency with
      conjunctival epithelialization, vascularization, and chronic inflammation. One
      month later, a complete keratectomy was performed in all eyes: 12 received
      additional transplantation of human amniotic membrane and heterologous limbal
      epithelial cells in a double amniotic membrane layer, 2 received amniotic
      membrane only, and 1 control eye received no procedure. RESULTS: After 1 month of
      follow-up, corneas in eight of the operated eyes presented minimal
      vascularization, without signs of rejection. Corneal surface reconstruction was
      demonstrated with the growth of new corneal-like epithelial phenotype and
      integration of amniotic membrane to the basal corneal surface. A superficial
      amniotic membrane (with the amnion side up as a dressing) peeled off after 7 to
      10 days. The epithelialization with heterologous limbal epithelial cells was
      evident underneath. The other four operated eyes were followed for 6 months; the
      ocular surface was also stable with a corneal-like epithelial phenotype.
      CONCLUSION: Simultaneous transplantation of amniotic membrane and heterologous
      limbal epithelial cells in severe ocular surface disorders could restore ocular
      surface and may be useful in patients with severe bilateral limbal epithelial
      loss, giving new perspectives for the treatment of severe ocular surface
      disorders.

PMID- 11333333
TI  - Clinical, surgical, and histopathologic characteristics of corneal keloid.
AB  - PURPOSE: To describe the cause, diagnosis, and management of a case of bilateral
      corneal keloid. METHODS: We describe a 17-year-old white boy with enlarging
      nontraumatic bilateral corneal scars whose growth was exacerbated by a
      superficial keratectomy. The patient underwent a penetrating keratoplasty (PK) in
      his left eye. Light and electron microscopy of the corneal button were performed.
      RESULTS: The histopathologic and ultrastructural features of the corneal button
      were haphazardly arranged collagen fascicles with activated fibroblasts but no
      inflammatory cells. The clinical outcome was excellent, although there has been
      continuous growth of the outer margin of the initial lesion not included in the
      PK. This growth has not affected vision. The unoperated right corneal lesion
      progressively enlarged during these years. CONCLUSION: A corneal keloid, although
      unusual, should be suspected in cases of enlarging white glistening avascular
      corneal scars regardless of a traumatic antecedent. Light and electron microscopy
      confirmed the diagnosis. Management is by PK when the visual axis is involved and
      carries an excellent prognosis.

PMID- 11333335
TI  - Bilateral conjunctival mucosa-associated lymphoid tissue lymphoma misdiagnosed as
      allergic conjunctivitis.
AB  - PURPOSE: This report aimed to discuss two nearly identical cases of primary
      conjunctival mucosa-associated lymphoid tissue (MALT) lymphoma mimicking allergic
      conjunctivitis. METHODS: Two patients were referred for intractability to
      conventional treatment of initial diagnoses of allergic conjunctivitis. On ocular
      examination, normally pigmented, giant papilla-like lesions were found
      bilaterally in the upper conjunctiva. Excisional biopsies were performed.
      RESULTS: Histopathologic and immunohistochemical examination of the conjunctival
      biopsies indicated MALT lymphoma in both patients. The patients subsequently
      received radiation therapy and achieved complete remission with no evidence of
      recurrence during follow-up periods of 13 and 11 months. CONCLUSION: Conjunctival
      low-grade lymphoma may share similar clinical features with allergic
      conjunctivitis. Ophthalmologists should be concerned that primary conjunctival
      low-grade malignant lymphoma can be misdiagnosed as allergic conjunctivitis

PMID- 11333334
TI  - Photorefractive keratectomy for myopia in the setting of Thygeson's superficial
      punctate keratitis.
AB  - PURPOSE: To describe a patient with Thygeson's superficial punctate keratitis who
      underwent photorefractive keratectomy for the correction of myopia. METHODS: A 49
      year-old woman with unilateral Thygeson's keratitis was examined before and after
      photorefractive keratectomy. RESULTS: A myopic patient underwent photorefractive
      keratectomy in the left eye and gained 20/20 uncorrected visual acuity. Seventeen
      months after surgery, symptomatic Thygeson's keratitis lesions recurred in the
      peripheral but not the central cornea. CONCLUSION: Photorefractive keratectomy
      reliably corrected myopia in a patient with previous Thygeson's keratitis. The
      recurrence of lesions only in the peripheral untreated cornea suggests that the
      inflammatory signal in Thygeson's keratitis may reside in the superficial corneal
      stroma.

PMID- 11333336
TI  - Successful treatment of dry eye in two patients with chronic graft-versus-host
      disease with systemic administration of FK506 and corticosteroids.
AB  - PURPOSE: We present two cases of severe dry eye in patients with chronic graft
      versus-host disease (CGVHD) after hematopoietic stem cell transplantation (SCT)
      who were successfully treated by the systemic administration of FK506 and
      corticosteroids. METHODS AND RESULTS: A 29-year-old man with chronic myelogenous
      leukemia underwent SCT. Oral and lung CGVHD developed on approximately day 130,
      and dry eye associated with CGVHD was diagnosed on day 168. The patient began
      receiving cyclosporin A (150 mg/d) for the treatment of oral and lung CGVHD.
      Treatment with prednisolone (1 mg/kg/d) began on approximately day 300. Oral and
      lung GVHD improved slightly, but worsened again although systemic administration
      of cyclosporin A and prednisolone were continued. Cyclosporin A was discontinued,
      and systemic administration of FK506 was started on day 376. Forty-four days
      later, marked improvement in the ocular surface and other organs was observed.
      However, the dry eye worsened while tapering FK506, with no flare of other
      affected organs. A 43-year-old woman with myelodysplastic syndrome underwent SCT.
      She received FK506 for prophylaxis of CGVHD. She had mild dry eye before SCT.
      Oral and intestinal CGVHD developed, and the dry eye worsened significantly on
      approximately day 150 while tapering FK506. Treatment with prednisolone (1
      mg/kg/d) began, and the dose of FK506 was increased. By day 240, the symptoms of
      dry eye and the findings of the ocular surface markedly improved, and CGVHD in
      other organs was completely resolved. However, the improvement in the dry eye was
      lost when FK506 was tapered for the second time. CONCLUSION: Systemic
      administration of FK506 with corticosteroids is an effective treatment of severe
      dry eye in patients with CGVHD, but long-term administration may be required to
      achieve a lasting response. These cases also suggest that further investigation
      into the use of topical FK506 and prednisolone as a maintenance therapy should be
      pursued.

PMID- 11333337
TI  - Ultrasound biomicroscopy in the management of posttraumatic scleral cyst.

PMID- 11333338
TI  - Corneal marginal infiltration with ulcerative colitis: a case report.

PMID- 11333339
TI  - Propionibacterium acnes as a cause of visually significant corneal ulcers.

PMID- 11333340
TI  - In vitro pharmacodynamics of ofloxacin and ciprofloxacin against common ocular
      pathogens.

PMID- 11333342
TI  - Leflunomide and methotrexate.
AB  - Methotrexate and leflunomide are both effective drugs in the treatment of
      patients with rheumatoid arthritis. Methotrexate has been available for many
      years, whereas leflunomide is a relatively new drug. Several large trials
      describing its efficacy and safety in comparison with both sulfasalazine and
      methotrexate and with placebo have been published recently. It appears that
      leflunomide is approximately equally effective as sulfasalazine and methotrexate.
      New data are also available on the mechanism of action of leflunomide especially.
      This drug probably acts as an immunomodulatory agent by interfering with the de
      novo synthesis of pyrimidines.

PMID- 11333343
TI  - Anti-tumor necrosis factor therapies.
AB  - Recently published studies confirm that the long-term use of biologicals
      targeting tumor necrosis factor-alpha (TNF-alpha) in therapy for rheumatoid
      arthritis (RA) gives rise to sustained improvement in symptoms and signs of
      disease provided the anti-TNF agent is efficacious and of low immunogenicity. The
      current regimens for infliximab 3 or 10 mg/kg infusion in combination with weekly
      oral methotrexate, or of etanercept 25 mg subcutaneously twice per week, appear
      to fulfill these criteria. D2E7, a "human" antibody produced by phage display,
      has also been used for over a year. It has recently emerged that anti-TNF therapy
      protects joints from structural damage. The 1-year data for infliximab and
      methotrexate combination therapy suggest that this regimen reduces disability. In
      early RA, etanercept acts more rapidly than methotrexate to decrease symptoms and
      retard the progression of erosions. In conclusion, for patients with established
      and early RA, anti-TNF therapies set a new standard for symptom control and joint
      protection.

PMID- 11333344
TI  - Anti-interleukin-1 therapy in rheumatic diseases.
AB  - Recent research has shown that in the processes of rheumatoid arthritis (RA),
      interleukin (IL)-1 is one of the pivotal cytokines in initiating disease, and the
      body's natural response, IL-1 receptor antagonist (IL-1Ra), has been shown
      conclusively to block its effects. In laboratory and animal studies inhibition of
      IL-1 by either antibodies to IL-1 or IL-1Ra proved beneficial to the outcome. To
      date, two large well-controlled studies in patients with RA led to the conclusion
      that IL-1Ra is clinically effective and that it slows progression of bone damage
      as measured radiographically. Being a specific, selective inhibitor of the IL-1
      pathway, IL-1Ra could constitute an important new approach to treating patients
      with RA that significantly reduces the signs and symptoms of the disease, reduces
      joint destruction and up to now has proved safe and well tolerated.

PMID- 11333345
TI  - Combination therapy in rheumatoid arthritis.
AB  - It has become clear that early suppression of rheumatoid arthritis disease
      activity is important in preventing progressive joint destruction and functional
      decline. To achieve this goal, many rheumatologists today advocate a more
      aggressive approach, using combinations of classic disease-modifying
      antirheumatic drugs-often including methotrexate-or new drugs. During the last 2
      years, the combination of methotrexate, sulfasalazine, hydroxychloroquine, and
      prednisolone has been demonstrated to be more beneficial than monotherapy in
      patients with early rheumatoid arthritis. In addition, the superior efficacy of
      the combination of new tumor necrosis factor-alpha blocking agents plus
      methotrexate to methotrexate alone in patients with chronic disease is very
      promising. Most studies of combination therapy focus on the efficacy of a
      combination compared with monotherapy, rather than on the efficacy of a treatment
      strategy. Although these studies of combination therapy provide useful
      information about the possible synergistic action of combinations of drugs, many
      questions remain unanswered, and studies evaluating different treatment
      strategies are needed before a new approach can be suggested.

PMID- 11333346
TI  - Autoimmune vestibulo-cochlear disorders.
AB  - Autoimmune vestibulo-cochlear disorders (AVCD) represent a group of syndromes
      with overlapping clinical features, manifesting as sensorineural hearing loss,
      often associated with vertigo, tinnitus, and aural fullness, and believed to be
      caused by an autoimmune mechanism. Although definitive evidence of a classic
      "autoimmune process" is still lacking, substantial indirect evidence has
      accumulated to strongly indicate such a pathogenesis. Rapidly progressing AVCD is
      analogous to rapidly progressive glomerulonephritis in that inner ear
      inflammation progresses to severe, irreversible damage within 3 months of onset
      (and often much more quickly). Thus patients with rapidly progressive AVCD are
      treated with a sense of urgency. Prompt treatment with corticosteroids and other
      antirheumatic/immunosuppressive agents can preserve hearing and vestibular
      functions. We are not aware of any randomized controlled clinical trials
      evaluating the efficacy of antirheumatic/immunosuppressive agents in AVCD. In
      this article we review reports of various therapies that have been tried in this
      condition and our experience of etanercept therapy in AVCD.

PMID- 11333347
TI  - Rheumatoid arthritis.

PMID- 11333348
TI  - Approaches to rheumatoid arthritis in 2000.
AB  - The year 2000 was characterized by euphoria among clinicians based on the
      continued and consolidated success of tumor necrosis factor (TNF) inhibition but
      also by problems caused by the high cost of this therapy. Looking at the risks
      and adverse effects has only begun, and there is so far a remarkable lack of
      publications dealing with this topic. Leflunomide also emerges as an established
      disease-modifying antirheumatic drug (DMARD). Other therapies include the
      cyclooxygenase-2 (Cox-2) inhibitors, which are tolerated better by the
      gastrointestinal system but raise concerns regarding thromboembolism in patients
      at risk. The enthusiasm regarding Cox-2 inhibitors is somewhat tempered by recent
      reports of thromboembolic complications, although those have been rare. The
      advances in research regarding mechanisms of inflammation and pathogenesis
      continue to generate new therapeutic approaches, which, however, remain mostly
      experimental. The complexity of genetics has been emphasized by reports on
      susceptibility and severity relation to TNF, mannose-binding lectin, and gamma
      interferon polymorphism. Epidemiologic studies focusing on prevalence, incidence
      and outcome continue to deliver conflicting messages. One major worry relates to
      chronic inflammation in RA and other rheumatic diseases as putative cause of
      accelerated atherosclerosis.

PMID- 11333349
TI  - Chemokines and angiogenesis.
AB  - Chemokines mediate the ingress of leukocytes, including neutrophils and
      monocytes, into the inflamed synovium. Among the four known chemokine families, C
      X-C and C-C chemokines seem to be of outstanding importance in this process.
      Angiogenesis, the formation of new vessels, is also important in the pathogenesis
      of rheumatoid arthritis. In this review, the authors discuss the role of the most
      important chemokines in the pathogenesis of rheumatoid synovitis. The most
      relevant angiogenic factors and angiogenesis inhibitors involved in rheumatoid
      arthritis are also discussed. Because certain chemokines may also play a role in
      neovascularization, chemokines and the process of angiogenesis are described in
      this context as well. Apart from discussing the pathogenic role of these factors,
      the authors also review the important relevance of chemokines and angiogenesis
      for therapeutic intervention.

PMID- 11333351
TI  - Have the new drugs relieved the burden of the orthopedic surgeon?
AB  - Rheumatoid arthritis (RA) represents a chronic joint inflammation that leads to
      destructive lesions of joint cartilage and periarticular bone. Increased
      understanding of the molecular and cellular mechanisms of RA and recent
      advantages in molecular technology have resulted in new antirheumatic drugs such
      as tumor necrosis factor-alpha blockers, inhibitors of interleukin-1, and novel
      disease-modifying antirheumatic drugs such as leflunomide. This review summarizes
      the important effects of the novel antirheumatic drugs and their potential impact
      on the work of orthopedic surgeons. The ability of these agents not only to
      improve the clinical signs and symptoms of RA but also to prevent progressive
      joint damage promises support to the work of orthopedic surgeons and to the
      interdisciplinary treatment of RA patients. The challenge, however, will be to
      conduct studies that show the concrete way in which the single drugs may best
      relieve the burden of the orthopedic surgeon.

PMID- 11333350
TI  - One-year inhibition of tumor necrosis factor-alpha: a major success or a larger
      puzzle?
AB  - The concept suggesting the involvement of the proinflammatory cytokine tumor
      necrosis factor (TNF)-alpha in the pathogenesis of rheumatoid arthritis (RA) has
      been demonstrated by several clinical trials targeting TNF-alpha. In addition to
      reduction of pain and swelling, a dramatic effect of TNF blocking therapies on
      the progression of joint destruction was shown. Nevertheless, complete remissions
      of the disease are rare even with these powerful therapeutic agents, and the
      optimal doses and dosage intervals of TNF blockers remain to be determined. Some
      insights into the pathogenesis of RA are provided by studying the effects of
      therapeutic TNF blockade on the biology of the disease. The fact that
      inflammation is not completely halted and destruction is ongoing in some patients
      suggests that other mechanisms may also be involved, including other cytokines
      such as interleukin-1 and interleukin-6. In addition to the necessity of
      understanding the pathogenic events proximal to TNF-alpha induction,
      pharmacologic intervention with small molecules in the TNF signaling pathways may
      constitute a promising strategy.

PMID- 11333353
TI  - Calcium crystal-induced inflammation.
AB  - Recent studies have added to our knowledge regarding the mechanisms of calcium
      crystal deposition. Calcium pyrophosphate dihydrate (CPPD) crystal deposition is
      associated with elevated levels of PPi in joints. Cyclic compression of cartilage
      transiently elevated ATP levels in culture media. Extracellular ATP may be
      hydrolyzed by nucleoside triphosphate pyrophosphohydrolase (NTPPPH), yielding an
      elevated PPi concentration. CPPD crystal deposition increases with age. Nitric
      oxide may alter cartilage matrix by interfering with chondrocyte mitochondrial
      function and ATP production. Transglutaminase in adult, but not young, porcine
      articular chondrocytes was able to activate latent transforming growth factor
      beta, a potent stimulus to PPi production. Basic calcium phosphate crystals are
      more likely to form in a milieu of reduced PPi concentration. The ank gene
      mutation results in higher intracellular PPi concentration and lower
      extracellular concentration. The ANK protein is thought to be a transmembrane
      protein necessary for transport of PPi out of cells. A mutation that results in
      reduced synthesis of NTPPPH PC-1 caused infantile wrist and ankle periarticular
      calcification and vascular calcification.

PMID- 11333354
TI  - Familial calcium crystal diseases: what have we learned?
AB  - The spectrum of heterotopic calcification or ossification is expanding because of
      the reports of several kindreds with calcium pyrophosphate deposition disease,
      apatite deposition disease, and others with less common syndromes associated with
      extracellular matrix calcification, such as fibrodysplasia ossificans progressiva
      and related syndromes. Genomic DNA studies in both humans and mice provide a
      shortcut to understanding the genetic basis of promotion and prevention of ECM
      calcification. Mutation in the COL2A1 gene has been identified in one family with
      spondyloepiphyseal dysplasia and calcium pyrophosphate and apatite crystalline
      deposits. In another kindred with precocious osteoarthritis without
      spondyloepiphyseal dysplasia, the phenotype was linked to markers of chromosome
      8. In four other kindreds, the phenotypes were linked to an area of chromosome
      5p. Two genes located in this region, which are expressed in articular cartilage,
      are being investigated as possible calcium pyrophosphate deposition disease
      genes. The results of linkage studies in three kindreds with
      articular/periarticular ADD with the COL2A1 gene were noninformative. Two
      different mouse mutations, the ank/ank and the ttw/ttw mice, are associated with
      intra-articular and ligament apatite deposits caused by a decrease in
      extracellular pyrophosphate concentrations, mimicking human arthritis caused by
      apatite deposition disease. Mutations in the matrix GLA protein, both in mice and
      in humans, are also associated with vascular and articular calcification. These
      mouse mutations provide cutting-edge information in the investigation of the
      mechanisms of apatite deposition in humans.

PMID- 11333355
TI  - Gout: diagnosis, pathogenesis, and clinical manifestations.
AB  - Gout is a common form of arthritis, in which many of the risk factors,
      pathogenetic mechanisms, and clinical features have been recognized for years.
      Nevertheless, new information has become available regarding the normal
      physiologic role of uric acid as an antioxidant, and greater insight has been
      obtained regarding the inflammatory process in acute gout. New studies have
      improved our understanding of the role of genetic and environmental factors
      responsible for hyperuricemia, and we know more about the significance of the
      association of hyperuricemia with other diseases. Clinically, rare complications
      and disease manifestations in new populations continue to be discussed, and
      diagnostic methods continue to be refined.

PMID- 11333356
TI  - Gout: can management be improved?
AB  - Ongoing reviews of Cochrane collaboration show that there is still very little
      reliable information based on randomized controlled trials on which to base
      treatment decisions in acute and chronic gout. Recent studies have stressed that
      avoidance of factors contributing to development of gouty attacks such as
      diuretic therapy, weight gain, and alcohol consumption may lead to a decrease in
      gouty arthritis. Attention to minidose aspirin and its effect on serum uric acid
      levels was addressed. A low carbohydrate, high protein and unsaturated fat diet
      was recommended for gouty patients since they all enhance insulin sensitivity and
      therefore may promote a reduction in serum uric acid levels. Treatment of gout in
      transplant recipients brings into focus some of the issues regarding management
      of gout, because gout is a common problem among transplant patients.

PMID- 11333357
TI  - Astrocyte-specific expression of aquaporin-9 in mouse brain is increased after
      transient focal cerebral ischemia.
AB  - Aquaporin-9 (AQP9) is a new member of the aquaporin family of water-selective
      channels mainly expressed in liver and testis, presenting the characteristic of
      also being permeable to various solutes, particularly lactate. Recent data have
      shown the presence of AQP9 on tanycytes in the rat brain. In the current study,
      the authors show the expression of AQP9 in astrocytes in the mouse brain and
      changes in its expression after cerebral ischemia. Indeed, in control mouse, the
      AQP9 immunolabeling is present on astrocytic processes bordering the subarachnoid
      space and ventricles. The labeling also is observed on astrocytes in the white
      matter, hippocampus, hypothalamus, and lateral septum. After focal transient
      ischemia, an increase of the immunolabeling is detected on astrocytes in
      periinfarct areas. This AQP9 distribution study in mouse brain suggests a role of
      AQP9 in water homeostasis in the central nervous system. Furthermore, the
      overexpression of AQP9 on astrocytes surrounding an ischemic lesion suggests that
      AQP9 may also play a role in the regulation of postischemia edema and, in view of
      its permeability to monocarboxylates, in the clearance of lactate from the
      ischemic focus.

PMID- 11333358
TI  - Differentiation of glucose transport in human brain gray and white matter.
AB  - Localized 1H nuclear magnetic resonance spectroscopy has been applied to
      determine human brain gray matter and white matter glucose transport kinetics by
      measuring the steady-state glucose concentration under normoglycemia and two
      levels of hyperglycemia. Nuclear magnetic resonance spectroscopic measurements
      were simultaneously performed on three 12-mL volumes, containing predominantly
      gray or white matter. The exact volume compositions were determined from
      quantitative T1 relaxation magnetic resonance images. The absolute brain glucose
      concentration as a function of the plasma glucose level was fitted with two
      kinetic transport models, based on standard (irreversible) or reversible
      Michaelis-Menten kinetics. The steady-state brain glucose levels were similar for
      cerebral gray and white matter, although the white matter levels were
      consistently 15% to 20% higher. The ratio of the maximum glucose transport rate,
      V(max), to the cerebral metabolic utilization rate of glucose, CMR(Glc), was 3.2
      +/- 0.10 and 3.9 +/- 0.15 for gray matter and white matter using the standard
      transport model and 1.8 +/- 0.10 and 2.2 +/- 0.12 for gray matter and white
      matter using the reversible transport model. The Michaelis-Menten constant K(m)
      was 6.2 +/- 0.85 and 7.3 +/- 1.1 mmol/L for gray matter and white matter in the
      standard model and 1.1 +/- 0.66 and 1.7 +/- 0.88 mmol/L in the reversible model.
      Taking into account the threefold lower rate of CMR(Glc) in white matter, this
      finding suggests that blood--brain barrier glucose transport activity is lower by
      a similar amount in white matter. The regulation of glucose transport activity at
      the blood--brain barrier may be an important mechanism for maintaining glucose
      homeostasis throughout the cerebral cortex.

PMID- 11333359
TI  - Insulin-like growth factor-1 reduces postischemic white matter injury in fetal
      sheep.
AB  - Insulin-like growth factor-1 (IGF-1) is known to be important for oligodendrocyte
      survival and myelination. In the current study, the authors examined the
      hypothesis that exogenous IGF-1 could reduce postischemic white matter injury.
      Bilateral brain injury was induced in near-term fetal sheep by 30 minutes of
      reversible carotid artery occlusion. Ninety minutes after ischemia, either
      vehicle (n = 8) or a single dose of 3 microg IGF-1 (n = 9) was infused
      intracerebroventricularly over 1 hour. White matter changes were assessed after 4
      days recovery in the parasagittal intragyral white matter and underlying corona
      radiata. Proteolipid protein (PLP) mRNA staining was used to identify bioactive
      oligodendrocytes. Glial fibrillary acidic protein (GFAP) and isolectin B-4
      immunoreactivity were used to label astrocytes and microglia, respectively.
      Myelin basic protein (MBP) density and the area of the intragyral white matter
      tracts were determined by image analysis. Insulin-like growth factor-1 treatment
      was associated with significantly reduced loss of oligodendrocytes in the
      intragyral white matter (P < 0.05), with improved MBP density (P < 0.05), reduced
      tissue swelling, and increased numbers of GFAP and isolectin B-4 positive cells
      compared with vehicle treatment. After ischemia there was a close association of
      PLP mRNA labeled cells with reactive astrocytes and macrophages/microglia. In
      conclusion, IGF-1 can prevent delayed, postischemic oligodendrocyte cell loss and
      associated demyelination.

PMID- 11333360
TI  - Adenosine in relation to calcium homeostasis: comparison between gray and white
      matter ischemia.
AB  - In vitro studies suggest that adenosine may attenuate anoxic white matter damage
      as an intrinsic protective substance. The authors investigated ischemic
      alterations of purines in relation to tissue depolarization and extracellular
      calcium and amino acid concentrations in vivo using microdialysis and ion
      selective electrodes in cortical gray and subcortical white matter of 10 cats
      during 120 minutes of global brain ischemia. Immediately on induction of
      ischemia, regional cerebral blood flow ceased in all cats in both gray and white
      matter. The direct current potential rapidly decreased, the decline being slower
      and shallower in white matter. Extracellular calcium levels decreased in gray
      matter. In contrast, they first increased in white matter and started to decrease
      below control levels only after approximately 30 minutes. Adenosine levels
      transiently increased in both tissue compartments; the peak was delayed by 30
      minutes in white matter. Thereafter, levels declined faster in gray than in white
      matter and remained elevated in the latter tissue compartment. Inosine and
      hypoxanthine elevations were progressive in both regions but smaller in white
      matter. Levels of gamma-aminobutyric acid, another putatively protective agent,
      steadily increased, starting immediately in gray matter and delayed by almost 1
      hour in white matter. The delayed and prolonged accumulation of adenosine
      correlates with a slower adenosine triphosphate breakdown in white matter
      ischemia and may result in protection of white matter by suspending cellular
      calcium influx.

PMID- 11333361
TI  - Dynamic changes in cerebral blood flow, O2 tension, and calculated cerebral
      metabolic rate of O2 during functional activation using oxygen phosphorescence
      quenching.
AB  - Changes in cerebral blood flow (CBF) using laser-Doppler and microvascular O2
      oxygen tension using oxygen-dependent phosphorescence quenching in the rat
      somatosensory cortex were obtained during electrical forepaw stimulation. The
      signal-averaged CBF response resulting from electrical forepaw stimulation
      consisted of an initial peak (t = 3.1 +/- 0.8 seconds after onset of
      stimulation), followed by a plateau phase that was maintained throughout the
      length of the stimulus. In contrast, microvascular O2 tension changes were
      delayed, reached a plateau level (t = 23.5 +/- 1.7 seconds after the onset of
      stimulation) that remained for the length of the stimulus and for several seconds
      after stimulus termination, and then returned to baseline. Using Fick's equation
      and these dynamic measurements, changes in the calculated cerebral metabolic rate
      of oxygen (CMRO2) during functional stimulation were determined. The calculated
      CMRO2 response initially was comparable with the CBF, but with protracted
      stimulation, CMRO2 changes were approximately one-third that of CBF changes.
      These results suggest that a complex relation exists, with comparable changes in
      CBF and CMRO2 initially occurring after stimulation but excessive changes in CBF
      compared with CMRO2 arising with protracted stimulation.

PMID- 11333362
TI  - Systems analysis of functional magnetic resonance imaging data using a
      physiologic model of venous oxygenation.
AB  - The authors revisit a simple mathematical model, presented in previous work, that
      characterizes the response of cerebral venous oxygenation to changes in blood
      flow and oxygen consumption. This physiologically based model can qualitatively
      duplicate the results of several recent empirical studies in which other authors
      have tested the hypothesis of linearity in the functional magnetic resonance
      imaging (fMRI) response to task activation, in that the experimentally found
      nearly linear behavior of the system and also its subtle departures from
      linearity are both predicted by simulations of the model. The model is simple
      enough that its equations can be explicitly solved. Moreover, an amended model
      that incorporates a varying cerebral blood volume parameter is found to have
      similar if not better consistency with the empirical data; indeed, this
      "extended" model is shown to be solvable by the same differential equation as the
      authors' simple one, wherein the volume is fixed as a constant. These
      investigations lend further indirect support to the blood oxygen level-dependent
      hypothesis of venous deoxyhemoglobin as the primary mechanism for fMRI signal
      changes during task activation, as well as for the authors' simple system as a
      useful physiologic model thereof. Although the authors' mathematical model does
      not formally represent a linear system with respect to the flow input, its
      underlying linear character may help partially explain the "nearly" linear
      behavior of the fMRI response.

PMID- 11333363
TI  - Both caspase-dependent and caspase-independent pathways may be involved in
      hippocampal CA1 neuronal death because of loss of cytochrome c From mitochondria
      in a rat forebrain ischemia model.
AB  - In a rat forebrain ischemia model, the authors examined whether loss of
      cytochrome c from mitochondria correlates with ischemic hippocampal CA1 neuronal
      death and how cytochrome c release may shape neuronal death. Forebrain ischemia
      was induced by bilateral common carotid artery occlusion with simultaneous
      hypotension for 10 minutes. After reperfusion, an early rapid depletion of
      mitochondrial cytochrome c and a late phase of diffuse redistribution of
      cytochrome c occurred in the hippocampal CA1 region, but not in the dentate gyrus
      and CA3 regions. Intracerebroventricular administration of Z-DEVD-FMK, a
      relatively selective caspase-3 inhibitor, provided limited but significant
      protection against ischemic neuronal damage on day 7 after reperfusion. Treatment
      with 3 minutes of ischemia (ischemic preconditioning) 48 hours before the 10
      minute ischemia attenuated both the early and late phases of cytochrome c
      redistribution. In another subset of animals treated with cycloheximide, a
      general protein synthesis inhibitor, the late phase of cytochrome c
      redistribution was inhibited, whereas most hippocampal CA1 neurons never regained
      mitochondrial cytochrome c. Examination of neuronal survival revealed that
      ischemic preconditioning prevents, whereas cycloheximide only delays, ischemic
      hippocampal CA1 neuronal death. DNA fragmentation detected by terminal
      deoxytransferase-mediated dUTP-nick end labeling (TUNEL) in situ was largely
      attenuated by ischemic preconditioning and moderately reduced by cycloheximide.
      These results indicate that the loss of cytochrome c from mitochondria correlates
      with hippocampal CA1 neuronal death after transient cerebral ischemia in relation
      to both caspase-dependent and -independent pathways. The amount of mitochondrial
      cytochrome c regained may determine whether ischemic hippocampal CA1 neurons
      survive or succumb to late-phase death.

PMID- 11333364
TI  - Up-regulation of neuropilin-1 in neovasculature after focal cerebral ischemia in
      the adult rat.
AB  - During development, neuropilin-1 is a receptor for semaphorin 3a-mediated axonal
      guidance and for vascular endothelial growth factor (VEGF) promotion of
      angiogenesis. The authors measured neuropilin-1 expression in the adult ischemic
      brain using Northern blot, in situ hybridization, and immunohistochemistry.
      Neuropilin-1 mRNA was significantly up-regulated as early as 2 hours and
      persisted at least 28 days after focal cerebral ischemia. Acute up-regulation of
      neuropilin-1 mRNA primarily localized to the ischemic neurons. A marked increase
      in both mRNA and protein of neuropilin-1 was detected in endothelial cells of
      cerebral blood vessels at the border and in the core of the ischemic lesion 7
      days after ischemia, and neuropilin-1 gene expression persisted on these vessels
      for at least 28 days after ischemia. In these areas, neovascularization was
      detected using three-dimensional reconstructed images obtained from laser
      scanning confocal microscopy. Activated astrocytes also exhibited neuropilin-1
      immunoreactivity during 7 to 28 days of ischemia. Double immunofluorescent
      staining showed colocalization of neuropilin-1 and VEGF to cerebral blood vessels
      and activated astrocytes. These data suggest that in addition to its role in
      axonal growth, up-regulation of neuropilin-1, in concert with VEGF and its
      receptors, may contribute to neovascular formation in the adult ischemic brain.

PMID- 11333366
TI  - Manganese Superoxide Dismutase Affects Cytochrome c Release and Caspase-9
      Activation After Transient Focal Cerebral Ischemia in Mice.
AB  - Release of cytochrome c from mitochondria to cytosol is a critical step in the
      mitochondrial-dependent signaling pathways of apoptosis. The authors have
      reported that manganese superoxide dismutase (Mn-SOD) attenuated cytochrome c
      release and apoptotic cell death after focal cerebral ischemia (FCI). To
      investigate downstream to the cytochrome c-dependent pathway, the authors
      examined caspase-9 activation after transient FCI by immunohistochemistry and
      Western blotting in both wild-type and Sod2 -/+ mice. Mice were subjected to 60
      minutes of middle cerebral artery occlusion followed by 1, 2, 4, or 24 hours of
      reperfusion. Two hours after reperfusion, cytochrome c and caspase-9 were
      observed in the cytosol and significantly increased in Sod2 -/+ mutants compared
      with wild-type mice as shown by Western blotting. Immunofluorescent double
      labeling for cytochrome c and caspase-9 showed cytosolic cytochrome c 1 hour
      after transient FCI. Cleaved caspase-9 first appeared in the cytosol at 2 hours
      and colocalized with cytochrome c. Terminal deoxynucleotidyl transferase-mediated
      uridine 5;-triphosphate-biotin nick and labeling (TUNEL) showed significant
      increase of positive cells in Sod2 -/+ mice compared with the wild-type in the
      cortex, but not in the caudate putamen. The current study revealed Mn-SOD might
      affect cytochrome c translocation and downstream caspase activation in the
      mitochondrial-dependent cell death pathway after transient FCI.

PMID- 11333365
TI  - Early c-Fos induction after cerebral ischemia: a possible neuroprotective role.
AB  - The role of c-Fos in neurodegeneration or neuroprotection after cerebral ischemia
      is controversial. To investigate whether early c-Fos induction after ischemia is
      associated with neuroprotection, rats were subjected to 10 minutes of transient
      forebrain ischemia and c-Fos expression was examined. Resistant dentate granule
      cells and neurons in CA2-4 displayed more robust immunoreactivity than vulnerable
      neurons in the CA1 region of hippocampus during early hours of reperfusion. By 6
      hours after reperfusion, c-Fos immunoreactivity was greatly diminished in all
      areas of the hippocampus. Administration of N-acetyl-O-methyldopamine (NAMDA), a
      compound previously shown to protect CA1 neurons against ischemia, increased c
      Fos immunoreactivity in the CA1 vulnerable region at 6 hours after ischemia and
      protected SK-N-BE(2)C neurons from oxygen glucose deprivation. Further in vitro
      study showed that NAMDA potentiated phorbol-12 myristate-13 acetate (PMA)-induced
      c-Fos expression, AP1 binding activity, and late gene expression determined by
      chloramphenicol acetyltransferase (CAT) activity from AP1 containing tyrosine
      hydroxylase promoter-CAT fusion gene in SK-N-BE(2)C neurons. In vivo and in vitro
      results showed that a neuroprotectant, NAMDA, in concert with another stimulus
      (for example, ischemia or PMA) up-regulates c-Fos expression and suggested that
      the early rise of NAMDA-induced c-Fos expression in vulnerable CA1 neurons may
      account for neuroprotection by means of up-regulating late gene expression for
      survival.

PMID- 11333367
TI  - Hyperglycemia enhances DNA fragmentation after transient cerebral ischemia.
AB  - Previous histopathologic results have suggested that one mechanism whereby
      hyperglycemia (HG) leads to exaggerated ischemic damage involves fragmentation of
      DNA. DNA fragmentation in normoglycemia (NG) and HG rats subjected to 30 minutes
      of forebrain ischemia was studied by terminal deoxynucleotidyl transferase
      mediated DNA nick-labeling (TUNEL) staining, by pulse-field gel electrophoresis
      (PFGE), and by ligation-mediated polymerase chain reaction (LM-PCR). High
      molecular weight DNA fragments were detected by PFGE, whereas low molecular
      weight DNA fragments were detected using LM-PCR techniques. The LM-PCR procedure
      was performed on DNA from test samples with blunt (without Klenow polymerase) and
      3'-recessed ends (with Klenow polymerase). In addition, cytochrome c release and
      caspase-3 activation were studied by immunocytochemistry. Results show that HG
      causes cytochrome c release, activates caspase-3, and exacerbates DNA fragments
      induced by ischemia. Thus, in HG rats, but not in control or NGs, TUNEL-stained
      cells were found in the cingulate cortex, neocortex, thalamus, and dorsolateral
      crest of the striatum, where neuronal death was observed by conventional
      histopathology, and where both cytosolic cytochrome c and active caspase-3 were
      detected by confocal microscopy. In the neocortex, both blunt-ended and stagger
      ended fragments were detected in HG, but not in NG rats. Electron microscopy (EM)
      analysis was performed in the cingulate cortex, where numerous TUNEL-positive
      neurons were observed. Although DNA fragmentation was detected by TUNEL staining
      and electrophoresis techniques, EM analysis failed to indicate apoptotic cell
      death. It is concluded that HG triggers a cell death pathway and exacerbates DNA
      fragmentation induced by ischemia.

PMID- 11333368
TI  - Apparent diffusion coefficient decreases and magnetic resonance imaging perfusion
      parameters are associated in ischemic tissue of acute stroke patients.
AB  - Perfusion-and diffusion-weighted magnetic resonance imaging scans are thought to
      allow the characterization of tissue at risk of infarction. The authors tested
      the hypothesis that the apparent diffusion coefficient (ADC) decrease should be
      associated with the severity of the perfusion deficit in ischemic tissue of acute
      stroke patients. Perfusion-and diffusion-weighted scans were performed in 11
      patients with sudden onset of neurologic deficits within the last 6 hours and T2
      weighted magnetic resonance imaging scans were obtained after 6 days. Parameter
      images of the maximum of the contrast agent concentration, time to peak, relative
      cerebral blood volume, relative cerebral blood flow, and relative mean transit
      time were computed from the perfusion-weighted data. A threshold function was
      used to identify tissue volumes with stepwise ADC decreases. An onionlike
      distribution of successively decreasing ADC values was found, with the lowest ADC
      in the center of the ischemic region. Correspondingly, tissue perfusion decreased
      progressively from the periphery toward the ischemic core. This effect was most
      pronounced in the time-to-peak maps, with a linear association between ADC
      decrease and time-to-peak increase. Apparent diffusion coefficient values
      decreased from the periphery toward the ischemic core, and this distribution of
      ADC values was strongly associated with the severity of the perfusion deficit.

PMID- 11333369
TI  - Inhibition of voltage-dependent sodium channels suppresses the functional
      magnetic resonance imaging response to forepaw somatosensory activation in the
      rodent.
AB  - Results of recent studies suggest that the glutamate-glutamine neurotransmitter
      cycle between neurons and astrocytes plays a major role in the generation of the
      functional imaging signal. In the current study, the authors tested the
      hypothesis that activation of voltage-dependent Na(+) channels is involved in the
      blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging
      (fMRI) responses during somatosensory activation. The BOLD fMRI and cerebral
      blood flow (CBF) experiments were performed at 7 Tesla on alpha-chloralose
      anesthetized rats undergoing forepaw stimulation before and for successive times
      after application of lamotrigine, a neuronal voltage-dependent Na+ channel
      blocker and glutamate release inhibitor. The BOLD fMRI signal changes in response
      to forepaw stimulation decreased in a time-dependent manner from 6.7% +/- 0.7%
      before lamotrigine injection to 3.0% +/- 2.5% between 60 and 105 minutes after
      lamotrigine treatment. After lamotrigine treatment, the fractional increase in
      CBF during forepaw stimulation was an order of magnitude less than that observed
      before the treatment. Lamotrigine had no effect on baseline CBF in the
      somatosensory cortex in the absence of stimulation. These results strongly
      suggest that activation of voltage-dependent Na+ channels is involved in the BOLD
      fMRI responses during somatosensory activation of the rat cortex.

PMID- 11333370
TI  - Within-session and between-session reproducibility of cerebral sensorimotor
      activation: a test--retest effect evidenced with functional magnetic resonance
      imaging.
AB  - The aim of the current study was to assess the reproducibility of functional
      magnetic resonance imaging (fMRI) brain activation signals in a sensorimotor task
      in healthy subjects. Because random or systematic changes are likely to happen
      when movements are repeated over time, the authors searched for time-dependent
      changes in the fMRI signal intensity and the extent of activation within and
      between sessions. Reproducibility was studied on a sensorimotor task called "the
      active task" that includes a motor output and a sensory feedback, and also on a
      sensory stimulation called "the passive task" that assessed the sensory input
      alone. The active task consisted of flexion and extension of the right hand. The
      subjects had performed it several times before fMRI scanning so that it was well
      learned. The passive task consisted of a calibrated passive flexion and extension
      of the right wrist. Tasks were 1 Hz-paced. The control state was rest. Subjects
      naive to the MRI environment and non--MRI-naive subjects were studied. Twelve MRI
      naive subjects underwent 3 fMRI sessions separated by 5 hours and 49 days,
      respectively. During MRI scanning, they performed the active task. Six MRI-naive
      subjects underwent 2 fMRI sessions with the passive task 1 month apart. Three non
      -MRI-naive subjects performed twice an active 2-Hz self-paced task. The data were
      analyzed with SPM96 software. For within-session comparison, for active or
      passive tasks, good reproducibility of fMRI signal activation was found within a
      session (intra-and interrun reproducibility) whether it was the first, second, or
      third session. Therefore, no within-session habituation was found with a passive
      or a well-learned active task. For between-session comparison, for MRI-naive or
      non--MRI-naive subjects, and with the active or the passive task, activation was
      increased in the contralateral premotor cortex and in ispsilateral anterior
      cerebellar cortex but was decreased in the primary sensorimotor cortex, parietal
      cortex, and posterior supplementary motor area at the second session. The lower
      cortical signal was characterized by reduced activated areas with no change in
      maximum peak intensity in most cases. Changes were partially reversed at the
      third session. Part of the test-retest effect may come from habituation of the
      MRI experiment context. Less attention and stress at the second and third
      sessions may be components of the inhibition of cortical activity. Because the
      changes became reversed, the authors suggest that, beyond the habituation
      process, a learning process occurred that had nothing to do with procedural
      learning, because the tasks were well learned or passive. A long-term memory
      representation of the sensorimotor task, not only with its characteristics (for
      example, amplitude, frequency) but also with its context (fMRI), can become
      integrated into the motor system along the sessions. Furthermore, the pattern
      observed in the fMRI signal changes might evoke a consolidation process.

PMID- 11333371
TI  - Changes in human regional cerebral blood flow and cerebral blood volume during
      visual stimulation measured by positron emission tomography.
AB  - The hemodynamic mechanism of increase in cerebral blood flow (CBF) during neural
      activation has not been elucidated in humans. In the current study, changes in
      both regional CBF and cerebral blood volume (CBV) during visual stimulation in
      humans were investigated. Cerebral blood flow and CBV were measured by positron
      emission tomography using H(2)(15)O and (11)CO, respectively, at rest and during
      2-Hz and 8-Hz photic flicker stimulation in each of 10 subjects. Changes in CBF
      in the primary visual cortex were 16% +/- 16% and 68% +/- 20% for the visual
      stimulation of 2 Hz and 8 Hz, respectively. The changes in CBV were 10% +/- 13%
      and 21% +/- 5% for 2-Hz and 8-Hz stimulation, respectively. Significant
      differences between changes in CBF and CBV were observed for visual stimulation
      of 8 Hz. The relation between CBF and CBV values during rest and visual
      stimulation was CBV = 0.88CBF(0.30). This indicates that when the increase in CBF
      during neural activation is great, that increase is caused primarily by the
      increase in vascular blood velocity rather than by the increase in CBV. This
      observation is consistent with reported findings obtained during hypercapnia.

PMID- 11333372
TI  - Absolute quantification by positron emission tomography of the endogenous ligand.
AB  - The results of several recent papers have shown a significant influence of the
      endogenous neurotransmitters on the exogenous ligand kinetics measured by
      positron emission tomography. For example, several groups found that the
      percentage of D2 receptor sites occupied by the endogenous dopamine ranged from
      25% to 40% at basal level. An obvious consequence of this significant occupancy
      is that the ligand-receptor model parameters, usually estimated by a model that
      does not take into account the endogenous ligand (EL) kinetics, can be
      significantly biased. In the current work, the authors studied the biases
      obtained by using the multiinjection approach. The results showed that in the
      classical ligand-receptor model, the receptor concentration is correctly
      estimated and that only the apparent affinity is biased by not taking the EL into
      account. At present, all absolute quantifications of the EL have been obtained
      through pharmacologic manipulation of the endogenous transmitter concentration,
      which is often too invasive a method to be used in patients. A theoretical
      reasoning showed that a noninvasive approach is necessarily based on both the
      apparent affinity measurement and on a multiregion approach. The correlation
      between the receptor concentration and the apparent affinity, previously observed
      with some ligands, verifies these two conditions; thus, the authors suggest that
      this correlation could be the result of the EL effect. To test this assumption
      experimentally, the effect of reserpine-induced dopamine depletion on the
      interactions between the D2 receptor sites and the FLB 457 is studied. With
      untreated baboons, the apparent FLB 457 affinity was smaller in the receptor-rich
      regions (striatum) than in the receptor-poor regions. This discrepancy
      disappeared after dopamine depletion, strongly suggesting that this affinity
      difference was related to the EL effect. Therefore, the purpose of the current
      study was to test the ability to quantify the EL based on the observed
      correlation between the receptor concentration and the apparent affinity. This
      approach offers a method for estimating the percentage of receptor sites occupied
      by the EL and, if its affinity is known, the free EL concentration. From the data
      obtained using FLB 457 with baboons, the authors found that approximately 53% of
      the D2 receptor sites are occupied by dopamine in the striatum and that the free
      dopamine concentration is approximately 120 nmol/L at basal level. This approach
      is transferable to patients, because the experimental data are obtained without
      pharmacologically induced modification of the EL.

PMID- 11333373
TI  - The impact of cancer therapy on reproductive function.

PMID- 11333375
TI  - Pregnancy in transplant recipients.
AB  - A growing number of transplant recipients are women of reproductive age or
      children who will reach reproductive age. Thus, menstrual function and pregnancy
      increasingly are important issues because fertility is restored to women who were
      previously unable to conceive. To date, successful pregnancies have been reported
      in female recipients of kidney, liver, heart, pancreas-liver, bone marrow, and
      lung transplants. Women often become pregnant while being maintained on numerous
      medications, including immunosuppressive agents, and their care providers must be
      able to counsel and care for them. Information to date suggests that
      immunosuppressive medications are safe for use during pregnancy and are important
      in preventing maternal and fetal complications secondary to graft rejection.
      Although no formal guidelines have been established due to limited clinical
      experience, there are a few criteria that are commonly agreed on to improve the
      probability of a successful pregnancy outcome and the maintenance of graft
      function in transplant patients. Successful management of the pregnant transplant
      patient requires a cooperative effort between the obstetrician and transplant
      team.

PMID- 11333376
TI  - Congenital toxoplasmosis: a review.
AB  - Toxoplasmosis is caused by infection with the protozoan parasite Toxoplasma
      gondii. In the United States, approximately 85% of women of childbearing age are
      susceptible to acute infection with T. gondii. Acute infections in pregnant women
      may cause serious health problems when the organism is transmitted to the fetus
      (congenital toxoplasmosis), including mental retardation, seizures, blindness,
      and death. An estimated 400 to 4000 cases of congenital toxoplasmosis occur in
      the U.S. each year. Manifestations of congenital toxoplasmosis may not become
      apparent until the second or third decade of life. Serologic tests are used to
      diagnose acute infection in pregnant women, but false-positive tests occur
      frequently, therefore, serologic diagnosis must be confirmed at a reference
      laboratory before treatment with potentially toxic drugs should be considered.
      Much of congenital toxoplasmosis can be prevented by educating women of
      childbearing age and pregnant women to avoid eating raw or undercooked meat, to
      avoid cross-contamination of other foods with raw or undercooked meat, and to use
      proper cat-litter and soil-related hygiene.

PMID- 11333377
TI  - Vertical transmission of HIV from mother to child in sub-Saharan Africa: modes of
      transmission and methods for prevention.
AB  - The impact of the human immunodeficiency virus (HIV) epidemic in sub-Saharan
      Africa on future mortality rates of infants, children, and mothers, life
      expectancy, and economic growth is profound. Vertical transmission of HIV,
      transmission from mother to child, is a major factor in the increasing rates of
      HIV infection in sub-Saharan Africa. Vertical transmission of HIV occurs in
      utero, intrapartum during labor and delivery, and postpartum during breast
      feeding. Because of the large numbers of HIV-infected mothers in developing
      countries, the majority trials regarding prevention of vertical transmission of
      HIV have been conducted in sub-Saharan Africa. Thus, sub-Saharan Africa has
      become a human laboratory, which demonstrates both the successes and failures of
      preventative methods to reduce vertical transmission of HIV. This review
      summarizes the body of research dedicated to understanding the pathophysiology of
      vertical transmission of HIV and pharmacology of inhibition of vertical
      transmission of HIV. While many debate the ethics of conducting trials in
      developing countries where effective prevention modalities have been slow to be
      implemented for economic, social and political reasons, studies continue and
      researchers continue to discover therapies and preventative methods, which may
      reduce the future devastation of HIV both in sub-Saharan Africa and throughout
      the world.

PMID- 11333379
TI  - The omega-3 story: nutritional prevention of preterm birth and other adverse
      pregnancy outcomes.

PMID- 11333380
TI  - Nemaline myopathy caused by mutations in the muscle alpha-skeletal-actin gene.
AB  - Nemaline myopathy (NM) is a clinically and genetically heterogeneous disorder
      characterized by muscle weakness and the presence of nemaline bodies (rods) in
      skeletal muscle. Disease-causing mutations have been reported in five genes, each
      encoding a protein component of the sarcomeric thin filament. Recently, we
      identified mutations in the muscle alpha-skeletal-actin gene (ACTA1) in a subset
      of patients with NM. In the present study, we evaluated a new series of 35
      patients with NM. We identified five novel missense mutations in ACTA1, which
      suggested that mutations in muscle alpha-skeletal actin account for the disease
      in approximately 15% of patients with NM. The mutations appeared de novo and
      represent new dominant mutations. One proband subsequently had two affected
      children, a result consistent with autosomal dominant transmission. The seven
      patients exhibited marked clinical variability, ranging from severe congenital
      onset weakness, with death from respiratory failure during the 1st year of life,
      to a mild childhood-onset myopathy, with survival into adulthood. There was
      marked variation in both age at onset and clinical severity in the three affected
      members of one family. Common pathological features included abnormal fiber type
      differentiation, glycogen accumulation, myofibrillar disruption, and "whorling"
      of actin thin filaments. The percentage of fibers with rods did not correlate
      with clinical severity; however, the severe, lethal phenotype was associated with
      both severe, generalized disorganization of sarcomeric structure and abnormal
      localization of sarcomeric actin. The marked variability, in clinical phenotype,
      among patients with different mutations in ACTA1 suggests that both the site of
      the mutation and the nature of the amino acid change have differential effects on
      thin-filament formation and protein-protein interactions. The intrafamilial
      variability suggests that alpha-actin genotype is not the sole determinant of
      phenotype.

PMID- 11333382
TI  - [The prevalence of headache in a population of patients with coeliac disease].
AB  - INTRODUCTION: Headache is the commonest clinical symptom during childhood and
      adolescence, from a neurologist s point of view. The pathophysiology of migraine
      and tension headache involve personality and biochemical factors, such as
      serotonin, which are also common in coeliac disease. OBJECTIVE: To establish the
      prevalence of headache in children and adolescents with coeliac disease, and any
      possible relation between these conditions. PATIENTS AND METHODS: We made a
      randomized selection of 86 patients with coeliac disease. All were on gluten-free
      diets and had no current gastroenterological symptoms. They had direct interviews
      and full physical and neurological examinations. The diagnosis of headache was
      based on criteria of the International Headache Society in 1988. RESULTS: The
      average age was 12.71 +/- 4.5 years (range 5-24). Headache occurred in 34 (39.5%)
      of the 86 patients studied. In 18 cases (20.9%) headache was of tension type and
      in 16 (18.6%) of migraine type. Of the latter, 10 cases had auras and 6 did not.
      There was no significant sex difference. CONCLUSIONS: An increased prevalence of
      both migraine and tension headaches was observed in the coeliac patients studied
      as compared with data published in the literature. In the former patients there
      was also a lower frequency in histories of migraine in first degree family
      members. This data is probably related to the personality of the patient or to
      his family or social circumstances in the case of tension headaches. In the case
      of migraine it may be due to biochemical factors such as a lowered plasma
      serotonin, seen both in coeliac disease and in migraine.

PMID- 11333381
TI  - Niemann-Pick C1 disease: correlations between NPC1 mutations, levels of NPC1
      protein, and phenotypes emphasize the functional significance of the putative
      sterol-sensing domain and of the cysteine-rich luminal loop.
AB  - To obtain more information of the functional domains of the NPC1 protein, the
      mutational spectrum and the level of immunoreactive protein were investigated in
      skin fibroblasts from 30 unrelated patients with Niemann-Pick C1 disease. Nine of
      them were characterized by mild alterations of cellular cholesterol transport
      (the "variant" biochemical phenotype). The mutations showed a wide distribution
      to nearly all NPC1 domains, with a cluster (11/32) in a conserved NPC1 cysteine
      rich luminal loop. Homozygous mutations in 14 patients and a phenotypically
      defined allele, combined with a new mutation, in a further 10 patients allowed
      genotype/phenotype correlations. Premature-termination-codon mutations, the three
      missense mutations in the sterol-sensing domain (SSD), and A1054T in the cysteine
      rich luminal loop all occurred in patients with infantile neurological onset and
      "classic" (severe) cholesterol-trafficking alterations. By western blot, NPC1
      protein was undetectable in the SSD missense mutations studied (L724P and Q775P)
      and essentially was absent in the A1054T missense allele. Our results thus
      enhance the functional significance of the SSD and demonstrate a correlation
      between the absence of NPC1 protein and the most severe neurological form. In the
      remaining missense mutations studied, corresponding to other disease
      presentations (including two adults with nonneurological disease), NPC1 protein
      was present in significant amounts of normal size, without clear-cut correlation
      with either the clinical phenotype or the "classic"/"variant" biochemical
      phenotype. Missense mutations in the cysteine-rich luminal loop resulted in a
      wide array of clinical and biochemical phenotypes. Remarkably, all five mutant
      alleles (I943M, V950M, G986S, G992R, and the recurrent P1007A) definitively
      correlated with the "variant" phenotype clustered within this loop, providing new
      insight on the functional complexity of the latter domain.

PMID- 11333383
TI  - [Nemaline congenital myopathy:clinical features and histopathological findings in
      nine patients].
AB  - INTRODUCTION: Nemaline myopathy is a type of congenital myopathy which presents
      with hypotonia, muscle weakness which is predominantly proximal, lax ligaments,
      areflexia and skeletal deformities. It is characterized by the presence of
      intrasarcolemal or intranuclear rods which can be seen with the red color optical
      microscope using the Gomori technique, and a defect in the Z line of the
      sarcomere, detected on electron microscopy (EM). PATIENTS AND METHODS: A
      retrospective study of the cases of nemaline congenital myopathy diagnosed in our
      hospital between 1984 and 1997. All patients had clinical laboratory analysis
      (muscle enzymes), and electromyographic and histopathological (muscle biopsy)
      studies. In 5 cases EM was done. RESULTS: Nine patients, four males and five
      females were studied. Diagnosis was made during the first year of life in 7 cases
      (77.7%), and was characterized by hypotonia, severe areflexia and proximal muscle
      weakness, whilst the remainder were diagnosed in adolescence when they presented
      with a juvenile form of the disorder, with muscle weakness, amyotrophy and
      scoliosis. Muscle biopsy showed nemaline bodies in a variable proportion of
      fibres. Intranuclear rods were not identified in any case. In the 5 cases in
      which ultrastructural studies were done, alterations were detected in the Z line
      of the sarcomere. The immunohistochemical profile of the rods was positive for
      alphaactin. CONCLUSIONS: There are no clinical features which permit distinction
      from other forms of congenital myopathy, so muscle biopsy is necessary for
      diagnosis. There is great phenotype and prognostic variety in this disorder.

PMID- 11333384
TI  - [Localization of the epileptogenic zone by analysis of electroencephalographic
      dipole].
AB  - INTRODUCTION: In partial epilepsy with seizures which are resistant to drug
      treatment, better results may be obtained with surgery. This follows thorough
      assessment to identify the area of the brain responsible for the origin of the
      seizures, or the epileptogenic zone (EZ), and show that surgical operation will
      not cause neurological or cognitive damage which might handicap the patient.
      OBJECTIVE: This study analyses the value in diagnosis of electroencephalographic
      dipoles in delimitation of the EZ in patients with refractory partial epilepsy
      who are candidates for surgical treatment. PATIENTS AND METHODS: In 43 patients
      we made EEG recordings whilst at rest with their eyes shut during 15 minutes. The
      signal was analysed by digital EEG apparatus and a map drawn of cerebral
      electrical activity based on the maximum average amplitude of the epileptic
      spikes. The electric dipole equivalent to epileptiform activity between seizures
      was obtained using the programme for analysis of electroencephalographic sources
      BESA. The localization of the EZ by means of the dipole was compared with the
      results of EEG, MR, SPECT and seizure video-EEG using intracranial electrodes.
      RESULTS: The results of this study show that the dipole model used is highly
      sensitive for localization of EZ, and in cases in which the dipole and MR
      coincided, its sensitivity is similar to that of video-EEG during seizures.
      CONCLUSIONS: The model of dipole used in this study is of great help when
      indicating surgery for patients with drug-resistant epilepsy.

PMID- 11333385
TI  - [Cortico-subcortical electrophysiological study during the effects of
      benzodiazepines in patients with panic disorders].
AB  - INTRODUCTION: Tribute to Robert Heath, M.D. a pioneer in human implanted
      corticosubcortical microelectrodes. OBJECTIVES: We evaluate retrospective
      electroencephalography (EEG), local evoked potentials (LEP) and extracellular
      unitary activity (EUA) of patients with diagnosis of panic disorder in
      association of simple partial seizures. These patients had presences or absence
      of agoraphobia. They received treatment with clonazepam or diazepam. PATIENTS AND
      METHODS: Ten patients with implanted corticosubcortical were divided in two
      groups. The five patients of group A were treated with clonazepam and the five
      patients of group B with diazepam. RESULTS: Panic attacks showed EEG thetha
      activity, increased amplitude of the negative phase of LEP, and an increase in
      the frequency of EUA in cortico-subcortical organizations. This changes occurred
      in all organizations with exception of the inhibitory reticular substance. Panic
      disorder produced abundance of repetitive epileptiform discharges that could
      precipitate convulsive crisis. Both benzodiazepines were efficacious although
      results with clonazepam were observed earlier: at 7 to 14 days. Benzodiazepines
      increased corticosubcortical EEG beta activity, decreased amplitude of negative
      phase of LEP, and diminution in the frequency of EUA. This changes occurred with
      exception on the inhibitory reticular system. We postulate: a) That panic
      disorder hyperexcitability at the cortico-subcortical neuronal level may be the
      result of gabergic dysfunction, or alteration in neuroinhibitory mechanism
      through GABAA receptors, and through GABAB neuromodulator receptors, and b) That
      there is a direct correlation between GABA inhibitory basic mechanism and
      electroencephalographic beta activity. CONCLUSIONS: Panic disorder produces
      neuronal hyperexcitability by gabergic dysfunction both benzodiazepines were
      efficacious in treatment.

PMID- 11333386
TI  - [Association of peripheral facial paralysis in patients with human
      immunodeficiency virus infection].
AB  - INTRODUCTION: Neurological disorders are common in patients infected with the
      human immunodeficiency virus (HIV). The objective of this study is to show the
      possible association of peripheral facial paralysis (PFP) in persons who test
      positive for HIV, which because of the characteristics of outpatient management
      is important in basic medical attention. PATIENTS AND METHODS: The scope of our
      study included all patients observed in 1998 and the first six months of 1999 who
      had PFP, and in whom detailed clinical history, physical examination by a
      neurologist, laboratory tests and HIV serological tests were done. RESULTS: We
      found that 89.1% of the patients with PFP were seropositive. The facial paralysis
      showed similar characteristics to Bell s palsy, with complete recovery after four
      weeks in 66.6% of this group of patients. The seronegative patients also
      recovered completely but took longer to do so. In two cases the PFP was
      associated with obvious features of AIDS. CONCLUSIONS: In the literature reviewed
      we have not found such a large group of patients with PFP associated with HIV+.
      However, it is obvious that there is an increase in facial paralysis which is in
      proportion to the increase in HIV+ persons. The results of our study suggest to
      us that HIV should be tested for in patients with PFP.

PMID- 11333387
TI  - [The fundus oculi in the hemiplegic patient].
AB  - INTRODUCTION AND OBJECTIVE: The fundus oculi is useful for observation of the
      interior of the eye and the retina. This study establishes a relationship between
      patients with established cerebral infarcts and the results observed in their
      fundi. PATIENTS AND METHODS: A retrospective study of the clinical histories of
      177 patients seen in the rehabilitation department over a period of one year.
      RESULTS: The patients were aged between 29 and 85 years. The majority were men;
      101 patients (57.06%) had systolic-diastolic arterial hypertension. On study of
      the fundus oculi there was a predominance of alterations of the blood vessels of
      the retina due to vascular sclerosis (93.1%) but only 24.4% had frank alterations
      caused by arterial hypertension. CONCLUSIONS: We found a slight relation between
      arterial hypertension and the alterations observed in the fundus oculi of these
      patients.

PMID- 11333388
TI  - [Neurological form of onset in haemophagocytic lymphohistiocytosis].
AB  - INTRODUCTION: Haemophagocyte lymphohistiocytosis (HLH) is a hematological
      disorder, autosomal recessive and in which there is benign proliferation of
      histiocytes with intense phagocytic activity of hematopoietic cells. The clinical
      features include fever, pancytopenia, coagulation disorders, liver dysfunction,
      the presence of histiocytes and haemophagocytes in the bone marrow, lymph nodes,
      spleen and liver. The nervous system is always involved and sooner or later
      patients develop a nervous system disorder with variable symptoms which may
      include irritability, disorders of consciousness, convulsions, ataxia, nystagmus
      or signs of intracranial hypertension. CLINICAL CASE: Onset of the disease
      showing purely neurological features is rare. We therefore describe the case of
      an 8 month old baby with HLH with a purely neurological condition involving
      irritability, horizontal rapid eye movements and vertical saccadic movements of
      both eyes and focal convulsive seizures. Initial complementary examinations were
      normal, except for study of the CSF with a lowered protein level and cells
      (monocytes). Finding hepatosplenomegaly and pallor, together with the laboratory
      investigations, made it advisable to do a bone marrow punch biopsy to detect
      haemophagocytes which would be diagnostic of HLH. In spite of chemotherapy there
      was rapid neurological deterioration, with alterations of the white matter and
      hydrocephaly which required insertion of a ventriculo-peritoneal shunt. The
      patient died when he was 10 months old. CONCLUSIONS: The cases of HLH in which
      cerebromeningeal disorders alone precede systemic symptoms are extremely rare.
      Hence the interest in reporting this case, so that it may be borne in mind in
      other cases of acute neurological onset. In this case initially there was
      encephalitis alone, but this was rapidly followed by systemic complications.

PMID- 11333389
TI  - [Repeated strokes in a patient with a basilar artery aneurysm].
AB  - INTRODUCTION: The estimated prevalence of basilar dolichoectasia in the healthy
      general population is 50 per 100,000 inhabitants. The treatment of symptomatic
      cases is controversial. Strokes caused by it may be due to thrombosis of the
      perforating arteries, arterio-arterial emboli or a compressive mechanism.
      CLINICAL CASE: We present the case of a 68 year old woman with repeated stokes in
      which the vertebrobasilar territory was involved. On neuroimaging there was
      basilar dolichoectasia associated with aneurismal dilatation of both internal
      carotid arteries. The patient died of massive subarachnoid hemorrhage after
      starting heparin treatment. At necropsy the aneurysmic dilatation was confirmed
      together with signs of arteriosclerosis of the arteries of the circle of Willis.
      CONCLUSIONS: Since subarachnoid hemorrhage secondary to rupture of a
      dolichoectasia is exceptional, some authors support the use of permanent
      anticoagulation rather than platelet antiaggregation in patients with conditions
      due to ischemia, in which dilatation is limited to the basilar artery. However,
      this is not suitable for cases with associated fusiform aneuryms, or cases such
      as ours in which the dolichoectasia extends beyond the basilar artery, to become
      generalized throughout all the arteries of the circle of Willis.

PMID- 11333390
TI  - [Headache secondary to carbon monoxide poisoning].
AB  - INTRODUCTION: Chronic intoxication due to carbon monoxide (CO) is a condition in
      which the frequency is underestimated since the clinical features are
      nonspecific. It is important since serious neurological sequelae may result: an
      extrapyramidal syndrome, dementia or a vegetative state. The diagnosis is
      established when there are venous blood levels of carboxyhemoglobin greater than
      10%. Early treatment with hyperbaric O2 rapidly improves the symptoms and avoids
      the development of neurological sequelae. CLINICAL CASE: We report the case of a
      30 year old woman who was admitted to hospital for investigation into two
      episodes of loss of consciousness with vomiting and subsequent somnolence not
      accompanied by other neurological sequelae. For the previous eight months she had
      had daily pulsatile biparietal headaches, sometimes accompanied by a fainting
      feeling, nausea and vomiting. During her admission she remained asymptomatic and
      all neurophysiological, cardiological and neuroimaging studies were normal. The
      day after medical discharge she returned with the same clinical condition. A
      woman who lived with her and accompanied her also complained of similar symptoms.
      Venous gasometry showed raised levels of carboxyhemoglobin in both the patient
      (30.4%) and her companion (31.2%). Treatment with hyperbaric 100% O2 reverted the
      symptoms within a few hours. Later studies showed that the domestic gas burner
      was faulty. CONCLUSIONS: Occult CO intoxication causes headache which often
      requires differential diagnosis from psychiatric disorders and episodes of
      migraine. In patients with refractory nonspecific headache, irregular course and
      systemic symptoms, usually in winter, CO intoxication should be considered to be
      a possible cause. Diagnosis is based on finding venous blood levels of
      carboxyhemoglobin of over 10%. Early treatment avoids lesion of the globus
      pallidus and irreversible extrapyramidal sequelae.

PMID- 11333391
TI  - [Benign encephalitis of the brain stem].
AB  - INTRODUCTION: The secondary encephalitis disorders are due to an immunological
      mechanism which causes demyelinating lesions of the central and peripheral
      nervous systems, with very variable clinical features. The pathogenesis and
      localization of benign encephalitis of the brain stem and the Miller Fisher
      syndrome (MFS) are still subject to debate. It is suggested that they may both
      belong to different extremes of the same nosological spectrum known as the
      ophthalmoplegia-ataxia-areflexia syndrome. CLINICAL CASE: We report the case of
      an 11 year old boy with encephalitis of the brain stem who had electromyographic
      alterations compatible with the Guillain-Barre syndrome, and MR images
      characteristic of an acute demyelinating disorder of the brainstem. CONCLUSIONS:
      The encephalitis of the brain stem is an uncommon condition in children which
      leads to diagnostic difficulty at its onset, since this is similar in other
      disorders such as MFS, tumours, cerebrovascular accidents and less often in the
      initial stages of multiple sclerosis. The clinical course is very useful to
      distinguish between these conditions. MR is the imaging technique of choice for
      diagnosis in these patients. Although there is currently no specific treatment
      for post-infectious encephalitis, the use of high doses of immunoglobulins may be
      justified in view of the physiopathological origin of the condition.

PMID- 11333392
TI  - [Antiepileptic drugs and neuropathic pain].
AB  - INTRODUCTION: This article is a bibliographic review of the part currently played
      by antiepileptic drugs in the treatment of neuropathic pain, and knowledge of
      their specific actions according to the different physiopathogenic mechanisms
      suspected of being involved in this type of pain. DEVELOPMENT: Neuropathic pain,
      the result of neurological damage in part of the nerve transmission system for
      pain, is one of the commonest painful syndromes in clinical practice and is a
      challenge for both neurologists and pain specialists. In recent years there has
      been increasing interest in the antiepileptic drugs, which were already used in
      this context in the sixties. Interest has increased with new drugs and better
      understanding of the physiopathogenic mechanisms of pain. The poor, variable
      response of these conditions to different treatments and the complex relationship
      between aetiologies, mechanisms and symptoms make it advisable to modify the
      traditional approach to the treatment of these conditions, passing form the
      aetiology and topographical distribution to the probable mechanisms involved in
      each individual patient, adapting the treatment to the individual concerned.
      CONCLUSIONS: The antiepileptic drugs are one of the most promising approaches to
      the drug treatment of neuropathic pain. Their use as the sole treatment, or in
      combination with other treatment, in individual patients depends on better
      understanding of the mechanisms involved in the genesis and maintenance of
      neuropathic pain and how antiepileptic drugs act on these mechanisms.

PMID- 11333393
TI  - [Prognostic factors in head injuries].
AB  - INTRODUCTION AND OBJECTIVE: Establishment of the prognosis after traumatic brain
      damage is an important question for doctors, patients and their families, as well
      as for health organizations and insurers. The precision of the prognosis varies
      markedly according to the final objective of the prediction (mortality, severity
      and type of residual defects, return to work), apart from consideration of the
      many factors which may affect the clinical course after this type of lesion. Our
      study considers the current state of this question. DEVELOPMENT: We consider the
      main methodological difficulties in carrying out such studies and review the main
      variables affecting the prognosis in head injuries, divided into three general
      groups (severity and type of lesion, characteristics of the individual and
      variables depending on the context). Finally, we make general comments on the
      effect of multidisciplinary rehabilitation in relation to the functional
      prognosis and level of social and employment integration attained by the injured
      persons.

PMID- 11333394
TI  - [Electroencephalographic diagnosis of the idiopathic generalized epilepsies of
      childhood].
AB  - INTRODUCTION: The idiopathic generalized epilepsies of childhood form a
      heterogeneous group of epileptic syndromes, with certain clinical and
      electroencephalographic characteristics in common. From the onset, the seizures
      affect both cerebral hemispheres with generalized clinical expression and from
      the start there are bilateral electroencephalographic patterns during seizures.
      These epilepsies have no known causes, there is a genetic predisposition and
      relation to the age of onset. The electroencephalographic characteristics during
      and between seizures have points in common: the basal electroencephalographic
      activity is normal in all the epilepsies of this group, the paroxystic anomalies
      are generalized, synchronic and symmetrical, and are formed of bilateral
      discharges of spikes, multiple spikes, spikes and waves and multiple spikes and
      waves, with discharges at a frequency of 3 Hz or more. DEVELOPMENT: In this
      article we review the electroencephalographic characteristics during and between
      seizures of the idiopathic generalized epilepsies and epileptic syndromes of
      childhood, with particular emphasis on childhood absences, since we consider this
      to be the commonest and most representative of the idiopathic generalized
      epilepsies of infancy. CONCLUSIONS: We consider that the electroencephalographic
      aspects of epilepsies and the epileptic syndromes make up a factor of great
      importance as a help in confirmation in diagnosis.

PMID- 11333395
TI  - [Learning and memory].
AB  - INTRODUCTION: The paper briefly reviews current knowledge on learning and memory
      processes, considered at the behavioral, cognitive and neural levels.
      DEVELOPMENT: After establishing the distinction between different learning
      processes (behavioral learning, skill acquisition and information acquisition
      processes), the specific learning phenomena belonging to each of these varieties
      are analyzed. Associative learning is described as a behavioral (pavlovian
      conditioning and instrumental learning) and cognitive (predictive learning and
      categorization) process. Also described are the properties of perceptual and
      motor learning, as those of the processes by which cognitive skills (e.g., rule
      learning) are acquired. Then, the distinction between short-term and long-term
      memory is discussed, referring to short-term memory as a working memory system
      that assists the performance of a variety of thinking and reasoning tasks.
      Finally, the two main long-term memory theories are discussed, considering the
      semantic/episodic and implicit/explicit memory dichotomies.

PMID- 11333396
TI  - [Study of brain asymmetry with neurologically normal subjects: visual
      procedures].
AB  - OBJECTIVES: We present a revision of the technique of visual lateralization of
      stimuli as one approach to the study of brain asymmetry with regard to language.
      At the same time, we present a summary of the research carried out by our group
      using these techniques, reflecting not only the main results but also the most
      relevant methodological aspects. DEVELOPMENT: Brain asymmetry is a basic
      characteristic of the organization of the nervous system. In most of the
      principal psychological processes there exists a greater or lesser degree of
      hemispheric differentiation. Among these, language is possibly one of the
      processes most noticeably lateralized. One of the main approaches in this field
      is the study of neurologically normal subjects using techniques of visual
      lateralization of stimuli. Appropriate use of this technique requires a knowledge
      of the basic principles involved and of the methodological requirement, as well
      as the different types of tasks and stimuli, which can be adapted to these
      requirements. CONCLUSIONS: The technique of lateralization of visual stimuli has
      a long tradition as a procedure for the study of cerebral asymmetry for language
      and is within the possibilities of most laboratories. However, ensuring correct
      lateralization requires rigorous controls and this has to be taken into
      consideration in the selection and adaptation of the experimental paradigm to be
      used. Several of these paradigms are used in our research and our results provide
      evidence of the relative character of cerebral asymmetry and of the participation
      of the right hemisphere in lexico-semantic processing.

PMID- 11333397
TI  - [Selective attention deficit in schizophrenia].
AB  - OBJECTIVE: To evaluate the cognitive deficits which have been linked with
      schizophrenia, particularly those related to selective attention from a
      neurocognitive point of view. DEVELOPMENT: We present a concept of attention
      consistent with a system of control of information processing composed of a group
      of neurone networks which carry out specific functions. Some functions are
      related to visual orientation, while others are involved in executive functions
      which are at the root of many cognitive skills. The convergence of data from
      behaviour studies and those made available by neuroimaging techniques have
      facilitated the identification of neuroanatomical areas responsible for these
      functions. Thus, the posterior parietal lobe, superior colliculus and pulvinar
      nucleus of the thalamus are responsible for directing visual attention to
      different spatial locations. The singular cortex, parts of the medial prefrontal
      area and supplementary motor area will be involved in executive functions. The
      question arises as to whether schizophrenia is related to a general attention
      deficit or to specific deficits linked to the different attention neurone
      networks. In the studies reviewed attention tasks for the evaluation of
      facilitatory and inhibitory functions related to the different attention networks
      were used. CONCLUSIONS: The studies showed that schizophrenic patients present
      deficits in inhibitory mechanisms which depend on the executive attention
      network. These results may contribute to a better understanding of the cognitive
      problems which occur in schizophrenia and also to design more effective
      strategies for the treatment of this disorder.

PMID- 11333398
TI  - Regulation of the cycling of timeless (tim) RNA.
AB  - Circadian rhythms in Drosophila depend upon expression of the timeless (tim) and
      period (per) genes, which encode interacting components of the endogenous clock.
      These two clock genes show a robust circadian oscillation in transcription rate
      as well as RNA and protein levels. Transcriptional activation of both genes
      requires the basic helix-loop-helix (bHLH) PAS transcription factors dCLOCK
      (dCLK) and CYCLE (CYC), which bind E-box elements. We investigated the role of E
      box elements in regulating behavioral rhythmicity and tim gene expression. We
      show that mutation of the upstream E-box in the tim gene prevents the rescue by
      tim cDNA sequences of the arrhythmic tim(01) phenotype. RNA encoded by this
      mutated tim transgene fails to cycle and is expressed at low levels. While a tim
      transgene carrying a wild-type E-box restores behavioral rhythms, tim RNA levels
      are intermediate to those of the mutant E-box transgenic lines and wild type, and
      do not display high amplitude cycling. On the other hand, high-amplitude RNA
      cycling was consistently obtained with a tim transgene that contains genomic,
      rather than cDNA, sequences. To identify additional sequences that may be
      required for tim cycling, we investigated the role of an E-box in the first
      intron of the tim gene through cell culture experiments. In these experiments,
      the presence of this intron did not have any effect on the activation of tim
      transcription by dCLK/CYC. As the upstream E-box was implicated in activation by
      dCLK/CYC in cell culture, we assayed sequences containing this E-box for
      association with proteins in fly head extracts. These studies provide the first
      biochemical evidence for an in vivo complex containing dCLK and CYC that binds
      the tim upstream sequence and is detected at all times of day. Together, these
      data highlight molecular mechanisms that are critical for behavioral rhythms.

PMID- 11333399
TI  - Sex differences in progesterone receptor immunoreactivity in neonatal mouse brain
      depend on estrogen receptor alpha expression.
AB  - Around the time of birth, male rats express higher levels of progesterone
      receptors in the medial preoptic nucleus (MPN) than female rats, suggesting that
      the MPN may be differentially sensitive to maternal hormones in developing males
      and females. Preliminary evidence suggests that this sex difference depends on
      the activation of estrogen receptors around birth. To test whether estrogen
      receptor alpha (ER alpha) is involved, we compared progesterone receptor
      immunoreactivity (PRir) in the brains of male and female neonatal mice that
      lacked a functional ER alpha gene or were wild type for the disrupted gene. We
      demonstrate that males express much higher levels of PRir in the MPN and the
      ventromedial nucleus of the neonatal mouse brain than females, and that PRir
      expression is dependent on the expression of ER alpha in these regions. In
      contrast, PRir levels in neocortex are not altered by ER alpha gene disruption.
      The results of this study suggest that the induction of PR via ER alpha may
      render specific regions of the developing male brain more sensitive to
      progesterone than the developing female brain, and may thereby underlie sexual
      differentiation of these regions.

PMID- 11333400
TI  - Conditional ablation of neurones in transgenic mice.
AB  - Conditional targeted ablation of specific cell populations in living transgenic
      animals is a very powerful strategy to determine cell functions in vivo. This
      approach would be of particular value to study the functions of distinct neuronal
      populations; however, the transgene of choice for conditional cell ablation
      studies in mice, the herpes simplex virus thymidine kinase gene, cannot be used
      to ablate neurones as its principal mode of action relies on cell proliferation.
      Here we report that expression of the E.coli nitroreductase gene (Ntr) and
      metabolism of the prodrug CB1954 (5-aziridin-1-yl-2-4-dinitrobenzamide) to its
      cytotoxic derivative can be used to conditionally and acutely ablate specific
      neuronal populations in vivo. As proof of principal, we have ablated olfactory
      and vomeronasal receptor neurones by expressing Ntr under the control of the
      olfactory marker protein (OMP) gene promoter. We demonstrate that following
      CB1954 administration, olfactory and vomeronasal receptor neurones expressing the
      transgene were selectively eliminated from the olfactory epithelium (OE), and
      projections to the olfactory bulb (OB) were lost. The functional efficacy of cell
      ablation was demonstrated using a highly sensitive behavioural test to show that
      ablated mice had lost the olfactory ability to discriminate distinct odors and
      were consequently rendered anosmic. Targeted expression of Ntr to specific
      neuronal populations using conventional transgenes, as described here, or by
      "knock-in" gene targeting using embryonic stem cells may be of significant value
      to address the functions of distinct neuronal populations in vivo.

PMID- 11333401
TI  - Effect of chronic denervation and denervation-reinnervation on cytoplasmic
      creatine kinase transcript accumulation.
AB  - The extensor digitorum longus (EDL) and soleus muscles of adult mice were
      chronically denervated or denervated and allowed to reinnervate. Muscles were
      evaluated 1, 5, 14, 21, and 52 days after sciaticectomy. In terms of weight loss,
      myofiber atrophy, degeneration, and fibrosis, the soleus muscle was more affected
      than the EDL by chronic denervation. Fifty-two days after chronic denervation,
      the number of molecules of MCK/ng total RNA in both muscles (determined with
      competitive PCR) decreased, with the soleus muscle being more affected. At that
      stage, BCK mRNA levels in the denervated soleus were unchanged, but they were
      increased (>50%) in the EDL. Reinnervation restored MCK transcript accumulation
      in the EDL, whereas, in the soleus MCK, transcripts exceeded control values by
      57%, approaching levels in the reinnervated EDL. Despite restoration of MCK mRNA
      levels, the number of molecules of BCK mRNA/ng total RNA was four- to fivefold
      higher in reinnervated versus control muscles, suggesting that the genes encoding
      the CK mRNAs are not coordinately regulated in adult muscle. The role of
      denervation induced, fiber type changes in regulating CK mRNA accumulation has
      been evaluated. Electron microscopic analyses have established that fibrosis is
      not a factor that determines BCK mRNA levels in the chronically denervated or
      denervated-reinnervated muscles. CK isozyme analyses support the hypothesis that
      a greater proportion of BCK mRNA found in 52 day chronically denervated and
      denervated-reinnervated muscles is produced in myofibers vs. nonmuscle cells than
      in control muscles.

PMID- 11333402
TI  - Digger wasp versus cricket: mechanisms underlying the total paralysis caused by
      the predator's venom.
AB  - The data presented here describe neurophysiological experiments addressing the
      question of cellular mechanisms underlying the total paralysis of locomotor
      behavior in crickets occurring after being stung by females of the digger wasp
      species Liris niger. The Liris venom effects have been studied by both in vivo
      recordings from identified neurons of the well-described giant fiber pathway and
      in vitro recordings from cultured neurons isolated from the terminal ganglion of
      crickets. The total paralysis of the prey is characterized by a general block of
      action potential generation as well as by a block of synaptic transmission.
      Intracellular recordings from neurons in intact ganglia under single electrode
      voltage-clamp conditions, as well as whole-cell patch-clamp recordings from
      cultured cricket neurons consistently show that the block of action potential
      generation by the Liris venom is due to a block of voltage-gated sodium inward
      currents in neurons of the stung ganglia. Furthermore, our data provide evidence
      that the Liris venom also blocks calcium currents in identified neurosecretory
      neurons. On the other hand, outward currents are not affected by the Liris venom.
      The in vitro recordings suggest that the Liris venom contains active venom
      components, which, at least for the observed block of inward currents, do not
      require a metabolic modification. Because venom application does not affect the
      ACh-induced EPSPs in giant interneurons, the Liris venom does not seem to
      influence the postsynaptic ACh receptors. The possible pre- and postsynaptic
      sites of venom action and the functional consequences on synaptic transmission
      within the giant fiber system are discussed.

PMID- 11333403
TI  - NMDA receptor regulation of cell death in the rat olfactory bulb.
AB  - Cell death is widespread in the developing nervous system and is under complex
      regulation by numerous intra- and intercellular mechanisms. Blockade of the N
      methyl-D-aspartate (NMDA) subtype of glutamate receptor has been shown to promote
      cell death in the developing brain (Ikonomidou et al., 1999), suggesting that
      afferent functional activation is an important regulator of cell survival. The
      olfactory bulb, the first central relay for olfactory information from the nose,
      is well suited for examining the role of afferent activity in neuronal
      development. Functional deprivation is easily performed by surgical blockade of
      airflow to one side of the nasal passage, which results in dramatic alterations
      in postnatal development of the bulb (Brunjes, 1994), including enhanced neuronal
      loss (Frazier and Brunjes, 1988; Najbauer and Leon, 1995). The present report
      examined the specific role of NMDA receptor activation in regulating cell
      survival within the rat bulb. Pharmacological blockade of receptors with the
      noncompetitive channel blocker MK-801 (3 x 0.5 mg/kg i.p.) resulted in profound
      increases in cell death within 24 h. Furthermore, in contrast to other regions,
      where the effects of receptor blockade were confined to the first 2 postnatal
      weeks (Ikonomidou et al., 1999), enhancement of cell death was seen in the deeper
      granule cell-containing regions of the bulb with injections as late as postnatal
      day 28. In addition, the effects of MK-801 were much more dramatic than those
      seen after unilateral naris closure, suggesting that NMDA receptor activation may
      mediate additional survival pathways in the bulb beyond that provided by first
      nerve input.

PMID- 11333404
TI  - Development of inhibition by ephrin-A5 on outgrowth of embryonic spinal motor
      neurites.
AB  - The spinal motor pool maps systematically onto the surface of muscles. This map
      is detectable in rat embryonic muscles, and is partially restored after
      reinnervation. Recent evidence shows that either overexpression or deletion of
      the ephrin-A5 gene significantly disrupts the map, suggesting that ephrin-A5
      plays a critical role in the formation of this topography. Several studies have
      demonstrated that ephrin-A5 is a repulsive molecule in the nervous system,
      including the neuromuscular system. To examine the development of sensitivity of
      ventral spinal axons to this inhibitory ligand, slices of E11 to E15 embryonic
      rat spinal cords were cocultured with membranes derived from ephrin-A5-expressing
      cell lines. We detected a progressive expression of inhibition by ephrin-A5
      between E11 and E15. By E15, rostral and caudal spinal neurites showed clear
      differences in responsiveness to the ephrin-A5 ligand. Further, we found that at
      this age caudal neurites are more sensitive to changes of ephrin-A5 concentration
      along a gradient. In addition, growth cones of caudal, more than rostral,
      neurites tended to assume a collapsed shape in the presence of the ligand. These
      results demonstrate a progressive development of sensitivity to ephrin-A5, and
      suggest a divergence in this sensitivity between rostral and caudal spinal cord
      neurites. These results provide further insight into how subtle rostrocaudal
      differences in the development of sensitivity to ephrin-A5 may explain, in part,
      neuromuscular topography.

PMID- 11333406
TI  - Respiratory health of automobile workers and exposures to metal-working fluid
      aerosols: lung spirometry.
AB  - BACKGROUND: Despite substantial evidence that workers exposed to metal-working
      fluids (MWF) have increased respiratory morbidity, the few studies of chronic
      effects on lung function have not been conclusive. METHODS: Lung spirometry was
      measured and both current and past exposures to metal-working fluid (MWF)
      aerosols were estimated in this cross-sectional cohort of 1,811 male automobile
      workers. Satisfactory exposure data were available for 1,745 (96%): 239
      assemblers (never-exposed to MWF), 487 assemblers (previously exposed), 352
      machinists currently exposed to straight oils, 441 to soluble oils, and 226 to
      synthetic fluids. Operations were classified as either grinding or non-grinding
      machining. RESULTS: Current exposure was not found to be associated with either
      forced expiratory volume in 1 second (FEV(1)) or forced ventilatory capacity
      (FVC). Nor was past exposure to water-based fluids (soluble or synthetic MWF)
      related to pulmonary function. Past exposure to straight oils, however, was
      significantly associated with FVC. This association was more obvious among older
      workers and among workers who had never transferred from MWF exposed jobs to
      assembly. CONCLUSIONS: The magnitude of the association between FVC and lifetime
      exposure to straight MWF was slightly larger than the estimated cigarette effect,
      suggesting that the impact of an additional year of exposure to 1 mg/m(3) of
      mineral oil particulate in the thoracic particle size range, has the same impact
      on FVC as smoking one pack per day for one more year.

PMID- 11333407
TI  - A prospective study of lung function among boilermaker construction workers
      exposed to combustion particulates.
AB  - BACKGROUND: Given the evidence of both acute cross-shift and short-term
      decrements in lung function in boilermaker construction workers following
      occupational exposure to combustion particulates, we sought to determine whether
      exposure is associated with an annual loss in lung function. METHODS: As part of
      an ongoing investigation, we conducted a 2-year longitudinal study of lung
      function among 118 boilermakers. Exposure was assessed with a work history
      questionnaire. Spirometry measurements were performed annually. RESULTS: We found
      an association between annual FEV(1) and hours worked at a gas-fired plant during
      the previous year, beta = - 9.8 mls/100 hours worked (95% CI: - 16.0, - 3.5)
      after adjustment for age, baseline FEV(1) and cigarette smoking status. The
      adjusted association between FEV(1) and "ever" worked at a gas-fired plant was -
      99.7 mls (95% CI: - 154.8, - 44.5). There was also evidence of a negative
      association between FEV(1) and "ever" worked and hours worked at oil and coal
      fired plants. CONCLUSIONS: These data suggest an association between annual lung
      function loss and working at gas, coal and oil-fired plants. Further follow-up of
      this cohort of boilermakers is in progress.

PMID- 11333408
TI  - Cohort mortality study of Philadelphia firefighters.
AB  - BACKGROUND: Fire fighters are exposed to a wide variety of toxic chemicals.
      Previous studies have reported excess risk of some cancers but have been limited
      by small numbers or little information on employment characteristics. METHODS: We
      conducted a retrospective cohort mortality study among 7,789 Philadelphia
      firefighters employed between 1925 and 1986. For each cause of death, the
      standardized mortality ratios (SMRs) and 95% confidence intervals were estimated.
      We also compared mortality among groups of firefighters defined by the estimated
      number of career runs and potential for diesel exposure. RESULTS: In comparison
      with U.S. white men, the firefighters had similar mortality from all causes of
      death combined (SMR = 0.96) and all cancers (SMR = 1.10). There were
      statistically significant deficits of deaths from nervous system diseases (SMR =
      0.47), cerebrovascular diseases (SMR = 0.83), respiratory diseases (SMR = 0.67),
      genitourinary diseases (SMR = 0.54), all accidents (SMR = 0.72), and suicide (SMR
      = 0.66). Statistically significant excess risks were observed for colon cancer
      (SMR = 1.51) and ischemic heart disease (SMR = 1.09). The risks of mortality from
      colon cancer (SMR = 1.68), kidney cancer (SMR = 2.20), non-Hodgkin's lymphoma
      (SMR = 1.72), multiple myeloma (SMR = 2.31), and benign neoplasms (SMR = 2.54)
      were increased among firefighters with at least 20 years of service. CONCLUSIONS:
      Our study found no significant increase in overall mortality among Philadelphia
      firefighters. However, we observed increased mortality for cancers of the colon
      and kidney, non-Hodgkin's lymphoma and multiple myeloma. There was insufficient
      follow-up since the introduction of diesel equipment to adequately assess risk.

PMID- 11333409
TI  - An application of hierarchical regression in the investigation of multiple
      paternal occupational exposures and neuroblastoma in offspring.
AB  - BACKGROUND: We used hierarchical regression to study the effects of 46 paternal
      occupational exposures on the incidence of neuroblastoma in offspring. METHODS:
      The study population included 405 cases and 302 controls. The effect of each
      exposure was estimated using both conventional maximum likelihood and
      hierarchical regression. RESULTS: Using hierarchical regression, overall
      precision was greatly enhanced compared to the conventional analysis. In
      addition, adjustment of effect estimates based on prespecified prior
      distributions of the true effect parameters allowed a more consistent
      interpretation across the entire panel of exposures. Estimates for several metals
      and solvents were shrunk close to the null value, whereas estimates for several
      thinner solvents, diesel fuel, solders, wood dust, and grain dust remained
      moderately elevated. CONCLUSIONS: Hierarchical regression may mitigate some of
      the problems of the conventional approach by controlling for correlated
      exposures, enhancing the precision of estimates, and providing some adjustment of
      estimates based on prior knowledge.

PMID- 11333410
TI  - Farmworker reports of pesticide safety and sanitation in the work environment.
AB  - BACKGROUND: Migrant and seasonal farmworkers are at risk for occupational
      illnesses from pesticide exposure, and the effectiveness of pesticide safety
      regulations has not been evaluated. It is important to learn from farmworker
      safety experiences to develop effective measures to improve agricultural
      workplace safety. METHODS: Formative research included in-depth interviews with
      farmworkers, farmers, extension agents, and health care providers. Survey
      research included interviews with 270 minority farmworkers during 1998, and 293
      during 1999. RESULTS: Farmworkers and farmers hold different beliefs concerning
      pesticide safety which affect sanitation practices. Farmworkers report in survey
      data that farmers do not adhere to regulations mandating training and basic
      sanitation facilities. CONCLUSIONS: Several points of intervention are available
      to improve pesticide safety and sanitation. Additional regulation by itself is
      not an advantageous starting point. The emphasis for intervention must include
      educating farmers as well as farmworkers.

PMID- 11333411
TI  - Pregnancy outcome following exposure to shortwaves among female physiotherapists
      in Israel.
AB  - BACKGROUND: The findings of the few epidemiological studies on the possible
      association between shortwave diathermy use by pregnant physiotherapists and
      adverse pregnancy outcome are inconsistent. We investigated such an association
      among physiotherapists in Israel. METHODS: Individualized data on exposure to
      shortwaves, ultrasound, and heavy lifting were collected by questionnaires and
      telephone interviews. RESULTS: The 434 studied women included 930 pregnancies:
      175 ended in spontaneous abortions, 45 had fetal malformations, 47 were delivered
      prematurely, and 33 infants had low birth weight. The remaining 630 normal
      pregnancies comprised the control group. Univariate analysis showed that exposure
      to shortwaves was associated with a significantly increased odds ratio (O.R.) for
      congenital malformations (O.R. 2.24, CI 1.27-4.83, P =.006) and low birth weight
      (O.R. 2.99, CI 1.32-6,79, P =.006). This effect increased in a dose-related
      manner. After controlling for potential confounding variables, only low birth
      weight reached statistical significance (O.R. 2.75, CI 1.07-7.04, P =.03). From
      the potentially confounding variables tested, febrile disease during pregnancy
      was found to be significantly associated with low birth weight (O.R. 3.37, CI
      1.38-8.25, P =.01). CONCLUSIONS: The findings of our study suggest that
      shortwaves have potentially harmful effects on pregnancy outcome, specifically
      low birth weight.

PMID- 11333412
TI  - Methyl-tertiary-butyl-ether (MTBE) misclassified.
AB  - Methyl-tertiary-butyl-ether (MTBE) was introduced into motor fuels in 1992 to
      reduce carbon monoxide automotive emissions in areas where the National Ambient
      Air Quality Standards for CO were exceeded. At a meeting of the National
      Toxicology Program's Board of Scientific Counselors (2-3 December 1998), data
      were presented showing that exposure to MTBE caused increased incidence of liver
      tumors, renal adenomas, carcinomas and interstitial cell adenomas of the testes
      in male, and lymphomas and leukemia in female CD1 mice [National Toxicology
      Program, 1998]. Despite this evidence, the NTP Board defeated a motion to list
      MTBE as "Reasonably anticipated to be a human carcinogen" by a vote of 6 to 5.
      This decision directly contravenes rules and procedures previously established by
      NTP for assessing carcinogenicity of chemical compounds. Good public health
      policy dictates that the NTP Board conduct another review of MTBE with proper
      consideration of the criteria that have been established for listing agents as
      carcinogens. Millions of Americans who are exposed daily to this chemical deserve
      an unbiased evaluation of carcinogenic agents being introduced into the
      environment.

PMID- 11333413
TI  - RE: MTBE misclassified.

PMID- 11333414
TI  - Re: MTBE misclassified.

PMID- 11333415
TI  - RE: Mesothelioma and lung tumors attributable to asbestos among petroleum
      workers. Am. J. Ind. Med. 2000. 37:275-282.

PMID- 11333416
TI  - RE: Mesothelioma and lung tumors attributable to asbestos among petroleum
      workers. Am. J. Ind. Med. 2000. 37:275-282.

PMID- 11333419
TI  - RE: Mesothelioma and lung tumors attributable to asbestos among petroleum
      workers. Am. J. Ind. Med. 2000. 37:275-282.

PMID- 11333420
TI  - Acute confusional state in the elderly following hip surgery: incidence, risk
      factors and complications.
AB  - OBJECTIVE: To determine incidence and risk factors for the development of
      postoperative acute confusional state (ACS) in the elderly. DESIGN: A prospective
      cohort study. SETTING: University hospital. PATIENTS: One hundred and five
      consecutive patients without ACS at baseline who underwent hip surgery because of
      hip fracture or elective hip replacement. All patients were 60 years or older.
      MEASUREMENTS: All patients underwent preoperative and daily postoperative
      evaluation by a research psychiatrist. Standardized instruments were used for
      cognitive screening, baseline assessment of depression, screening for alcohol
      abuse, comorbidity, and functional status. ACS was diagnosed by using the
      Confusion Assessment Method (CAM). Additional medical data were taken from
      patients' charts and anaesthetic records. RESULTS: Postoperative ACS developed in
      23.8% of the study sample, in 40.5% of the hip fracture group and in 14.7% of the
      hip joint replacement group. The prevalence was highest between postoperative
      days 2 and 5. Multiple logistic regression analysis demonstrated the following
      risk factors of ACS: higher age (OR = 1.14, 95% CI 1.07-1.22), prior cognitive
      impairment as measured by Mini-Mental State Examination (OR = 1.32 for each point
      less, 95% CI 1.06-1.64), depression (OR = 3.67, 95% CI 1.12-12.02), low
      educational level (OR = 3.59, 95% CI 1.14-11.25), and preoperative abnormal
      sodium (OR = 4.32, 95% CI 1.01-18.38). Other risk factors showing statistically
      significant differences in the univariate analyses were: living in nursing home,
      vision or hearing impairment, higher comorbidity, regular use of psychotropic
      drugs before admission, fracture on admission, preoperative leucocytosis. A
      considerable proportion of patients with ACS showed self-destructive behaviour
      postoperatively, whereas self-destructive behaviour was not observed among non
      delirious patients. CONCLUSIONS: ACS is common among elderly hip surgery
      patients. The occurrence of ACS is influenced by several predisposing and
      precipitating factors. Further knowledge of these risk factors will contribute to
      the early identification of high risk patients and to the development of
      preventive measures.

PMID- 11333421
TI  - Contribution of PTSD/POW history to behavioral disturbances in dementia.
AB  - As many World War II and Korean Conflict veterans suffering from posttraumatic
      stress disorder (PTSD) grow older, increasing numbers will be diagnosed with
      dementia. We retrospectively analyzed patients with dementia, comparing the
      behavioral disturbances of those with PTSD to those without PTSD. We hypothesized
      that due to the additive effect of the neurobiological and behavioral changes
      associated with PTSD and dementia, the dementia with PTSD group would show more
      agitation and disinhibition than the dementia without PTSD group. Sixteen
      patients with diagnoses of dementia and PTSD were matched on age and Mini-Mental
      States Examination (MMSE) scores to 16 patients with dementia without PTSD.
      Demographic characteristics, co-morbid diagnoses, global Assessment of
      Functioning (GAF), Cohen-Mansfield Agitation Inventory (CMAI), and paranoid items
      of Brief Psychiatric Rating Scale (BPRS) and Positive and Negative Syndrome Scale
      for Schizophrenia (PANSS) were assessed. The patients with diagnoses of dementia
      with PTSD did not differ significantly in their clinical presentation, hospital
      course, and condition at discharge from patients with dementia without PTSD. Chi
      square analysis showed that significantly more subjects in the PTSD group were
      prescribed anti-depressants compared to the non-PTSD group. Interestingly, within
      the PTSD group, the subgroup of patients who were former prisoners of war had a
      significantly higher mean score for paranoia and significantly less verbal
      agitation. This pilot study reveals that a diagnosis of PTSD alone is not
      sufficient to influence behavior in veterans with dementia; however, we also
      present provocative results that patients with more severe trauma (POW) do have
      changes in their behavior.

PMID- 11333422
TI  - The association between depressive symptoms and cognitive decline in community
      dwelling elderly persons.
AB  - OBJECTIVE: To investigate whether depressive symptoms predict specific types of
      cognitive decline in order to elucidate the association between late life
      depression and cognitive decline. BACKGROUND: Mechanisms underlying the
      association between late life depression and cognitive decline are still unclear.
      METHOD: Six hundred and forty-one elderly persons of the Longitudinal Aging Study
      Amsterdam (LASA) aged 70-85 were examined by means of two measurement occasions
      over a period of 3 years. Depressive symptoms were assessed by means of the CES
      D. Various cognitive functions were examined using neuropsychological tests.
      RESULTS: Depressive symptoms were associated with decline in speed of information
      processing over a 3-year period, whereas there was no association between
      depression and increasing memory impairment or global mental deterioration.
      CONCLUSION: These findings suggest that depressive symptoms are associated with
      subcortical pathology, most probable white matter lesions.

PMID- 11333423
TI  - Behavioral profile of Alzheimer's disease in Chinese elderly--a validation study
      of the Chinese version of the Alzheimer's disease behavioral pathology rating
      scale.
AB  - OBJECTIVES: This study aims to examine the psychometric properties of the Chinese
      version of the Alzheimer's disease behavioral pathology rating scale (CBehave-AD)
      and the behavioral profile of Chinese patients with AD. METHODS: Seventy-one
      subjects with NINCDS-ADRDA diagnosis of probable and possible AD were assessed
      for validation of the CBehave-AD. A behavioral symptom frequency checklist, the
      Chinese version of the Blessed Roth dementia scale (CDS) and the Cantonese
      version of the Mini-Mental State Examination (CMMSE) were used for comparison. An
      extended sample of 120 AD patients was then evaluated with the CBehave-AD.
      RESULTS: High correlations between the CBehave-AD and checklist scores were found
      (paranoid and delusional ideation, hallucinations, activity disturbances,
      aggressiveness and diurnal rhythm disturbances). The scale also demonstrated
      satisfactory inter-rater and test-retest reliabilities. The mean (SD) CMMSE score
      of the 120 patients was 9.4 (7.1). Among them, 32% have delusions, 15% had
      hallucinations, 54% had activity disturbances, 61% had aggressive behavior, 44%
      had sleep disturbance, 24% had affective disturbances, 19% had anxiety and
      phobias. Delusional ideation was significantly associated with hallucinations,
      aggressiveness, and affective disturbances. Diurnal rhythm disturbances were
      associated with activity disturbances and aggressiveness. CBehave-AD total scores
      were not significantly correlated with severity of AD, but individual symptom
      categories showed different pattern of correlation. Delusions, hallucinations,
      anxiety and phobias were significantly correlated with dementia staging.
      CONCLUSION: The findings suggest that the CBehave-AD is a valid assessment tool
      for behavioral disturbances in patients with AD. Variable associations between
      different symptom categories and dementia staging suggest a need for further
      exploration of the complex interactions between behavioral and cognitive
      disturbances in dementia.

PMID- 11333424
TI  - Delirious mania in the elderly.
AB  - Delirious mania is a clinical syndrome in which the signs and symptoms of
      delirium manifest themselves in the context of a manic episode. Though there have
      been numerous descriptions and case reports of this syndrome, all have described
      mania as the presenting feature, with signs of delirium developing subsequently,
      and none of the vignettes have involved elderly patients. We report two cases of
      elderly individuals with mania who initially presented as in a delirium. Both of
      them experienced clear manic episodes, which were confirmed by their psychiatric
      histories and clinical responses to mood stabilizers. Mania needs to be in the
      differential diagnosis of elderly people presenting with confusion,
      disorientation, and perceptual changes, particularly in those with a history of
      bipolar disorder.

PMID- 11333425
TI  - Temporal patterns of disruptive vocalization in elderly nursing home residents.
AB  - This study used computer-assisted real-time data collection procedures to study
      temporal patterns of disruptive vocalization (DV) in demented nursing home
      residents. Residents (N = 68) were observed from 8 a.m. to 8 p.m. and total mean
      duration of DV within hourly blocks was calculated. Analysis of the temporal
      distribution of DV exhibited by the group of 68 residents indicated a significant
      cubic trend. Exploratory cluster analysis uncovered three distinct temporal
      patterns of DV; although two of the patterns are generally supportive of
      sundowning. Cluster 1 showed a relatively constant pattern of low rate DV.
      Clusters 2 and 3 showed cyclic trends. Peaks in DV were observed during noontime
      and in the evening for Cluster 2. Cluster 3 showed peaks in DV in the early
      morning hours and late afternoon. MANOVA was employed to examine any differences
      among clusters in age, cognitive status, and ADL status. Univariate analyses
      indicated that cognitive status was the only factor that differed significantly
      among clusters, with members of Cluster 1 (constant low rate DV) manifesting
      higher cognitive status scores than Clusters 2 and 3. A step-wise discriminant
      function analysis also showed cognitive status to be the only statistically
      significant predictor of cluster membership. The authors' note that the
      scientific literature on agitation is fraught with contradictory findings and
      assert that inconsistencies may be due to differences across studies in problem
      definition, method of measurement, and sample size. The results are discussed in
      relation to these methodological issues and clinical implications of the
      findings.

PMID- 11333426
TI  - The comparison of burden between caregiving spouses of depressive and demented
      patients.
AB  - BACKGROUND: The opportunities for a depressive or demented elderly patient to
      live at home are dependent on the availability of support. If the spouse is
      alive, her or his resources to care for the patient are an essential option. In
      this study we compared the burden of the spouses of depressive and demented
      elderly patients admitted to the University Psychogeriatric Clinic. METHODS: The
      Zarit Burden Interview was used when comparing the burden between the groups.
      Psychological distress was screened by the 12-item General Health Questionnaire.
      The care and support given by the spouse was assessed by Involvement Evaluation
      Questionnaire. The spouse's stress related to the health state of the patient was
      evaluated by the Pearlin Caregiving Stress Inventory. Twenty-two spouses living
      with a depressive patient and 43 with a demented patient were included in the
      study. RESULTS: The spouses of demented patients as a group were psychologically
      more stressed than the spouses of depressive patients. However, when demented
      patients were divided into two groups, in those admitted mainly for noncognitive
      symptoms related to dementia and in those admitted for memory assessment and
      diagnostic purposes, the burden of the spouses in the former group was higher
      than that of the group of depressive patients' spouses. No difference was found
      between the latter group of demented patient spouses and depressive patients'
      spouses. Both the patients and the spouses in the demented group were older than
      those in the depressive group. However, no correlation was found between stress
      of the spouse and her or his own age or the age of the patient either within the
      depressive or within the demented group. As expected, the function level of
      demented patients was lower than that of depressive patients. A correlation was
      found within both groups between low functional capacity of the patient and the
      stress of the spouse. In both groups the spouses who felt their own mental health
      to be poor were more likely to have high levels of burden. CONCLUSIONS: Among the
      general psychogeriatric patient groups, the caregiving spouses of demented
      patients with noncognitive psychiatric symptoms are the most burdened group.
      However, spouses of depressive patients are as much burdened as those of demented
      patients with mild to moderate memory impairment. More support is needed for
      every spouse group caring for psychogeriatric patients.

PMID- 11333427
TI  - A comparison of five clock scoring methods using ROC (receiver operating
      characteristic) curve analysis.
AB  - OBJECTIVE: To compare the accuracy of five clock scoring methods for detecting
      dementia in English-speaking patients. DESIGN: A prospective cohort study.
      SETTING: A general geriatric outpatient clinic in southwest Sydney, Australia.
      PARTICIPANTS: A total of 127 consecutive new referrals to the clinic, of mean age
      78.2 years. MEASUREMENTS: The clock drawing test was conducted at the beginning
      of each clinic appointment by a blinded observer. Each patient was then assessed
      by a geriatrician, who collected demographic data, administered the modified
      Barthel index, the geriatric depression scale, and the Folstein Mini-Mental State
      Examination, and categorised each patient as demented or not demented, according
      to DSM-4 criteria. Each clock was scored according to the methods of Mendez,
      Shulman, Sunderland, Watson and Wolf-Klein, and evaluated for reliability, and
      predictive accuracy, using receiver operating characteristic (ROC) curve
      analysis. RESULTS: The area under the ROC curve was largest for the Shulman
      (0.79, 95% CI 0.70-0.85) and Mendez (0.78, 95% CI 0.70-0.85) methods. Both
      predicted dementia more accurately than the Sunderland (area = 0.71) and Watson
      (area = 0.65) methods (p < 0.05). The inter-rater (0.81-0.93) and intra-rater
      (0.87-0.96) correlation coefficients were high for all five methods. CONCLUSIONS:
      While substantial differences among the clock scoring methods were evident in our
      sample, the accuracy of each was modest at best. Unless further studies in
      relevant settings suggest otherwise, we caution on the use of clock drawing alone
      to screen for dementia.

PMID- 11333428
TI  - Estimating the costs of informal care for people with Alzheimer's disease:
      methodological and practical challenges.
AB  - Although Alzheimer's disease and related disorders may have a heavy impact on
      informal caregivers, estimates of informal care costs have been neglected and
      when included in cost of illness studies, valuations have been highly variable.
      Although these variations are in part due to differences in samples and the
      difficulty in measuring caregiving time, this illustrates the need to standardise
      the methodology not only for valuing formal, but also informal care costs.
      Methods used for valuing informal care are identified, together with theoretical
      and practical challenges in measurement. In particular the measurement of time
      and it's associated satisfaction or utility is complex and valuations of time
      need to consider aspects of the caregiving experience which influence the
      marginal valuation of the time spent caring. More empirical work is required to
      elicit information on both the positive and negative satisfaction associated with
      caregiving and to incorporate this into valuations of the costs related to
      informal care.

PMID- 11333429
TI  - Development and validation of the Observation List for early signs of Dementia
      (OLD).
AB  - OBJECTIVE: Development and validation of a short Observation List of possible
      early signs of Dementia (OLD) for use in general practice. DESIGN: Stepwise
      development using reviews of publications and expert consensus. Field study for
      evaluation of reliability. Validation study (interviews, family forms) using
      existing valid and reliable measures. Use of data reduction techniques to
      construct a short version. Setting of field study Twenty-two GPs in 19 Dutch
      practices. PARTICIPANTS: The first two patients seen on 15 working days (n = 470)
      were observed. Inclusion: age > 75, without a known diagnosis of dementia.
      Exclusion: psychiatric treatment, severe depression, acute illness with
      confusion. Division of patients into three groups with no, intermediate, and the
      most signs (total of interviewed patients, n = 60; family forms, n = 39). Outcome
      measures Reliability (Cronbach's alpha and factor-analysis). Convergent validity
      using the Cognitive Screening Test (CST), the Word Learning Test (WLT, total and
      retention), the Informant Questionnaire on Cognitive Decline in the Elderly
      (IQCODE), the Groningen Activities Restriction Scale (GARS), and an IADL scale.
      Discriminant validity using the geriatric depression scale (GDS). Construct
      validity using a Principal Component Analysis (PRINCALS). Incremental validity
      using the intuitive opinion of the GP (McNemar test). RESULTS: Reliability in the
      total group 0.88, first factor explained variance 42.5%. Convergent validity (two
      way ANOVA) results: CST (p = 0.00), WLT-total (p = 0.001), WLT retention (p =
      0.00), IQCODE (p = 0.09). No statistically significant differences for GARS and
      IADL. GDS (p = 0.30) not different. PRINCALS first factor explained 48% of
      variance. The OLD added to the GP opinion (McNemar p = 0.00). Reliability short
      version 0.89 (interviewed group), 0.86 (total group). CONCLUSIONS: The OLD is a
      valid and reliable method to detect early signs of dementia in general practice
      that can indicate when it may be useful to employ existing screening instruments.

PMID- 11333430
TI  - Delirium in the non-demented oldest old in the general population: risk factors
      and prognosis.
AB  - BACKGROUND: The oldest old are prone to develop delirium. Studies into risk
      factors for delirium have been carried out predominantly in younger age groups.
      The aim of this population-based follow-up study was to investigate the risk
      factors for delirium requiring medical attention and subsequent prognosis in the
      non-demented general population aged > or = 85 years. METHOD: The study included
      the non-demented subjects in the population-based Vantaa 85+ study. After the 3
      year observation period, 199 subjects (91% of those surviving) were re-examined
      and their medical records were evaluated for episodes of delirium. The subjects
      were followed up with respect to mortality for another 2 years. RESULTS: During
      the 3-year observational period, 20 subjects (10%) had been diagnosed as having
      had an episode of delirium. A Mini-Mental State Examination score of < 24 (odds
      ratio (OR) 3.44, confidence interval (CI = 95%) 1.27-9.32) and high systolic
      blood pressure (OR 3.08, CI 1.08-8.79) were identified as independent risk
      factors for delirium. The association between the delirium episode and a new
      diagnosis of dementia was significant ( p = 0.001). The mortality rate was
      greater among those subjects who experienced delirium than among subjects without
      this syndrome ( p = 0.008). CONCLUSIONS: Mild cognitive impairment and high
      systolic blood pressure were found to be risk factors for delirium requiring
      medical attention in the general non-demented population aged > or = 85 years.
      The study also highlights the significant association between delirium and a new
      dementia diagnosis in this age group.

PMID- 11333431
TI  - Unequal distribution of cognitive deficits in vascular dementia--is this a valid
      criterion in the ICD-10?
AB  - OBJECTIVE: To investigate the appropriateness of the ICD-10 criterion for
      vascular dementia which requires unequal distribution of deficits between
      different domains of cognitive function. DESIGN: Cross-sectional comparative
      study. SETTING: Referrals to a specialist memory clinic in Sheffield and a
      community sample of patients from a general practice population in Melton
      Mowbray. METHOD: The CAMCOG part of the Cambridge mental disorders of the elderly
      examination (CAMDEX) was assessed for 131 Sheffield subjects and 396 Melton
      Mowbray subjects to examine both total variability and differences between
      individual subscale items. Depression was also examined as this was a potential
      confounding factor. RESULTS: After adjustment for age, sex and depression scores,
      there were no significant differences between vascular dementia subjects and
      Alzheimer's disease subjects at either centre for total variability of cognitive
      deficits and little difference between diagnoses for individual subscale items.
      In Sheffield, subjects with vascular dementia had significantly higher depression
      scores compared to those with Alzheimer's disease. CONCLUSIONS: The usefulness of
      the concept of unequal deficits as a diagnostic criterion for vascular dementia
      in routine clinical practice is doubtful.

PMID- 11333432
TI  - Temporal lobe-oriented CT scanning and dementia in Down's syndrome.
AB  - BACKGROUND: Although individuals with Down's syndrome (DS) are uniquely at risk
      of developing Alzheimer's disease, the diagnosis of dementia in DS is problematic
      because of the difficulty in detecting cognitive decline in individuals with pre
      existing learning disability. AIM: To determine if dementia in DS is associated
      with Medial Temporal Lobe (MTL) atrophy as measured by temporal lobe-oriented CT
      scanning. METHOD: Ten individuals with DS who were experiencing functional
      decline had CT scans with temporal lobe-oriented views. All individuals were
      assessed for the presence of dementia according to modified DSM-IIIR criteria.
      The minimal thickness of the MTL, corrected for age-related atrophy was measured
      using a computer calipers at the level of the mid-brainstem by a radiologist
      blind to the dementia diagnosis. RESULTS: All six individuals who met modified
      DSM-IIIR criteria for dementia showed significant MTL atrophy. CONCLUSIONS: The
      utility of temporal lobe-oriented CT scanning as an adjunct to the diagnosis of
      dementia in DS appears promising and warrants further study.

PMID- 11333433
TI  - Validating mini-mental status, cognitive capacity screening and Hamilton
      depression scales utilizing subjects with vascular headaches.
AB  - INTRODUCTION: The Mini-Mental State Examination (MMSE) and Cognitive Capacity
      Screening Examination (CCSE) are easily and rapidly administered tests for
      quantifying the general cognitive status of young as well as geriatric subjects.
      Likewise, the Hamilton Depression Rating Scale (HDRS) is a brief instrument for
      quantifying depression that may confound cognitive test performances. Testing by
      means of all three scales concurrently provides useful information for
      longitudinal research among the elderly. OBJECTIVES: To validate the combined
      longitudinal use of MMSE, CCSE and HDRS among a specific cohort of normal
      subjects with vascular headaches characterized by known well-established
      temporary cognitive decline occurring only during temporary intervals with
      headache. METHODS: The MMSE, CCSE and HDRS were serially tested at 3-12 monthly
      intervals among 196 healthy subjects attending our out-patient headache clinic
      who suffered from migraine or cluster headaches. Stability and specificity of
      MMSE, CCSE and HDRS were evaluated by comparing consecutive normative scores
      during headache-free intervals. Sensitivity of MMSE and CCSE for detecting
      temporary cognitive decline were evaluated by comparing scores during headache
      and headache-free intervals. RESULTS: CCSE, MMSE and HDRS gave stable headache
      free normative values over intervals of 3-10 years among 182 subjects. Among 77
      subjects during headache intervals, temporary cognitive decline were confirmed by
      both CCSE and MMSE (p < 0.0001). When cutoff points for both CCSE and MMSE normal
      scores were placed at >/= 27, specificity for detecting cognitively normal values
      for CCSE and MMSE when headache-free were 92.2 and 89.6%, respectively (p >
      0.05), while sensitivity for detecting cognitively decline during headache
      intervals were 83.7 and 49%, respectively (p < 0.001). Compared with scoring by a
      single rater, reliability estimates for all three rating scales were slightly
      lower when tested by different raters, but these differences were not
      significant. CONCLUSIONS: CCSE is reliable and more sensitive than MMSE for
      detecting cognitive decline.

PMID- 11333434
TI  - Is apolipoprotein e4 associated with cognitive decline in depression?

PMID- 11333436
TI  - Long-term memory correlates negatively with plasma transcobalamin in healthy
      elderly with normal plasma cobalamin levels.

PMID- 11333435
TI  - Apolipoprotein E epsilon4 allele is a risk factor for late-onset Alzheimer's
      disease and vascular dementia in Han Chinese.

PMID- 11333438
TI  - Organic ion imaging of biological tissue with secondary ion mass spectrometry and
      matrix-assisted laser desorption/ionization.
AB  - Organic secondary ion mass spectrometry (SIMS) and matrix-assisted laser
      desorption/ionization (MALDI) mass spectrometry can be used to produce molecular
      images of samples. This is achieved through ionization from a clearly identified
      point on a flat sample, and performing a raster of the sample by moving the point
      of ionization over the sample surface. The unique analytical capabilities of mass
      spectrometry for mapping a variety of biological samples at the tissue level are
      discussed. SIMS provides information on the spatial distribution of the elements
      and low molecular mass compounds as well as molecular structures on these
      compounds, while MALDI yields spatial information about higher molecular mass
      compounds, including their distributions in tissues at very low levels, as well
      as information on the molecular structures of these compounds. Application of
      these methods to analytical problems requires appropriate instrumentation, sample
      preparation methodology, and a data presentation usually in a three-coordinate
      plot where x and y are physical dimensions of the sample and z is the signal
      amplitude. The use of imaging mass spectrometry is illustrated with several
      biological systems.

PMID- 11333439
TI  - Advanced glycation end products: a highly complex set of biologically relevant
      compounds detected by mass spectrometry.
AB  - Structural information on 'AGE-peptides,' a class of substances belonging to
      advanced glycation end products (AGE) and originating by proteolysis of glycated
      proteins, was gained through various analytical approaches on the mixture
      produced by proteinase K digestion of in vitro glycated bovine serum albumin.
      Both matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) and
      high-performance liquid chromatography/electrospray ionization mass spectrometry
      (HPLC/ESI-MS) were employed, and the results were compared with those from
      conventional spectroscopic methods (UV, fluorescence, gel permeation). The data
      acquired by the various techniques all depict the digestion mixtures as highly
      complex, with components exhibiting molecular mass in the range 300-3500 Da. In
      the analysis of HPLC/ESI-MS data, identification of AGE-peptides was facilitated
      by 3D mapping. Structural information was gained by means of multiple mass
      spectrometric experiments.

PMID- 11333440
TI  - Discrimination between pentose oligosaccharides containing D-xylopyranose or L
      arabinofuranose as non-reducing terminal residue using fast atom bombardment mass
      spectrometry.
AB  - Collisional-induced dissociation (CID) mass spectra of the [M + H](+) and [M -
      H](-) ions obtained under fast atom bombardment conditions of a number of methyl
      glycoside di-, tri- and tetrasaccharides, containing D-xylopyranosyl and/or L
      arabinofuranosyl residues at the non-reducing terminus, do not provide
      information about their ring size. This information could only be obtained from a
      careful comparison of the intensity ratio of the [M + Na - 90](+) and [M + Na -
      104](+) ions ((0,2)X(t)/(1,5)X(t)) in the high-energy CID spectra of the sodium
      cationized di-, tri- and probably also tetrasaccharide compounds.

PMID- 11333441
TI  - Mass spectrometric analysis of recombinant adenylate cyclase toxin from
      Bordetella pertussis strain 18323/pHSP9.
AB  - The adenylate cyclase toxin-hemolysin (ACT) is a key virulence factor of the
      whooping cough agent Bordetella pertussis (Bp). The major cytotoxic activity of
      this 1706-residue protein consists of its capacity to invade a variety of
      eukaryotic cells directly across their cytoplasmic membrane and to deliver into
      cells a catalytic adenylate cyclase domain. This causes impairment of immune
      effector cells and apoptosis of lung macrophages by uncontrolled conversion of
      ATP to cAMP. The adenylate cyclase toxin-hemolysin acquires biological activity
      upon post-translational amide-linked palmitoylation of the epsilon-amino group of
      lysine 983 (K983) by the accessory fatty acyltransferase, CyaC. However, an
      additional conserved acylation site can be identified in ACT at lysine 860 (K860)
      and this residue is palmitoylated when recombinant ACT is produced in Escherichia
      coli (r-Ec-ACT). In this paper we report the double acylation of r-Bp-ACT
      secreted by a recombinant Bp strain 18323/pHSP9. This strain overproduces ACT
      from an oligocopy plasmid carrying the entire cya locus of Bordetella pertussis
      18323. Palmitoylation of both conserved lysines (K860 and K983) of r-Bp-ACT
      expressed by this Bp strain was found. In addition, an error in the deduced
      protein sequence was identified, with Leu being the real residue at position 1001
      and not the Val residue given in the published gene sequence. We also discuss
      these results in comparison with those from recombinant ACT expressed in E. coli
      strain K12 XL1-Blue. The analytical approach for characterization of the fatty
      acylation of ACT from strain 18323/pHSP9 consisted of multiple proteolytic
      digestion procedures (trypsin, Asp-N), microcapillary liquid
      chromatography/tandem mass spectrometry and matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry.

PMID- 11333443
TI  - Comparison between solution-phase stability and gas-phase kinetic stability of
      oligodeoxynucleotide duplexes.
AB  - The relative kinetic stabilities of different 16-mer oligonucleotide duplexes
      were investigated by source collision-induced dissociation (CID) in a heated
      capillary electrospray ion source. They were compared with the relative
      stabilities in solution obtained by thermal denaturation monitored by UV
      spectrophotometry. The results clearly show that both hydrogen bonding and base
      stacking interactions that are present in solution are maintained in the gas
      phase. This suggests that the electrospray process preserves the double-helix
      structure of DNA. A step by step opening of the double helix structure is
      proposed for the gas-phase dissociation, competing with the covalent bond
      cleavage of bases. We also draw attention to the fact that by source CID, it is
      the kinetic stability of the complexes that is probed. In particular, this
      implies that only complexes of the same size can be compared.

PMID- 11333444
TI  - Characterization of novel di- and tricarboxylic acids in fine tropical aerosols.
AB  - Three unknown di- and tricarboxylic acids were characterized in the fine size
      fraction of aerosols which were collected during the wet season in the Amazon
      basin (Rondonia, Brazil). For the structural characterization of the methyl
      esters of these unknown compounds, mass spectrometry with electron ionization
      (EI) and tandem mass spectral techniques combined with gas chromatographic (GC)
      separation were employed. Fragment and parent ion spectra were recorded during
      elution of the GC peaks by linked scanning of the B and E sectors in combination
      with high-energy collision-induced dissociation. The fragmentation patterns of
      significant ions in the first-order EI spectra were also obtained for nonanedioic
      acid, which was examined as a model compound. The compounds were tentatively
      identified as 4-acetyloxyheptanedioic acid and cis and trans isomers of 5-hexene
      1,1,6-tricarboxylic acid. Since there were indications of biomass burning during
      the aerosol sampling the di- and tricarboxylic acids characterized in the present
      work could be markers for biomass burning. Furthermore, the characterization of
      di- and tricarboxylic acids in the fine size fraction of atmospheric aerosols may
      be important for assessing the effects of organic aerosols in cloud formation.

PMID- 11333445
TI  - Determination of saccharides in fruit juices by capillary electrophoresis and
      matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.
AB  - A fast method for the detection of cheap sweeteners is presented. Detecting the
      adulteration of foods rich in carbohydrates is complicated by the presence of
      variety of commercial sweeteners that are designed to match exactly the major
      carbohydrate profiles of these foods. Electrophoretic and mass spectrometric
      assays for the determination of fruit juice authenticity were developed.
      Capillary zone electrophoresis with indirect detection was employed to detect
      adulteration of juices demonstrated by the ratio of the concentrations of major
      low molecular mass saccharides (glucose, fructose and sucrose). Traces of
      oligosaccharides, which are not present in the sugar profiles of citrus fruits
      but are present in inexpensive sweeteners, were evaluated as the other group of
      target compounds. The fast determination of oligomeric starch hydrolysates in a
      complex matrix was tested by matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry (MALDI-TOFMS) and applied to orange juice. MALDI-TOFMS
      was shown to be a suitable method for the identification of adulteration of fruit
      juices by starch hydrolysates. The effects of the presence of salts and low
      molecular mass saccharides on the detection of oligosaccharides by MALDI-TOFMS
      were studied. Low molecular mass saccharides and organic acids decrease the
      detectability of oligosaccharides by MALDI-TOFMS, but the concentration of
      maltooligosaccharides present in juices sweetened with starch hydrolysates is
      high enough to be detected with good sensitivity.

PMID- 11333448
TI  - Determination of purine compounds in carotid artery plaque by liquid
      chromatography electrospray ionization tandem mass spectrometry.

PMID- 11333449
TI  - Mass spectrometry for cultural heritage knowledge: gas chromatographic/mass
      spectrometric analysis of organic remains in Neolithic potsherds.

PMID- 11333450
TI  - Current literature in mass spectrometry.

PMID- 11333451
TI  - Infection in the aetiology of spondyloarthropathies.

PMID- 11333453
TI  - Second-line drug therapy for osteoarthritis.

PMID- 11333452
TI  - Tumour necrosis factor blockade in rheumatoid arthritis.

PMID- 11333454
TI  - Medical treatment at the end of life. A position statement.

PMID- 11333455
TI  - The enigma of consent.

PMID- 11333456
TI  - Improving the certification of death and the usefulness of routine mortality
      statistics.

PMID- 11333457
TI  - What is a consultant?

PMID- 11333458
TI  - The good doctor.

PMID- 11333459
TI  - Aspirin: past, present and future.
AB  - Many folk remedies used since pre-historic times have depended upon salicylates
      for their effect. One hundred years ago aspirin was formulated from salicylic and
      acetic acids. It was the first drug to be synthesised and its formulation is
      regarded as the foundation of the modern pharmaceutical industry. The benefit of
      low-dose aspirin as a prophylactic after a thrombotic event was first reported 25
      years ago. Its use after coronary or cerebral thrombosis is virtually mandatory,
      unless there are signs of intolerance. A 'loading dose' of soluble aspirin should
      be given on first contact with a patient who may be suffering from myocardial
      infarction. Patients considered to be at increased risk of a vascular event
      should also be advised to carry their own aspirin and, if they experience sudden
      severe chest pain, to chew and swallow a 300 mg tablet or a soluble preparation
      immediately. The current phase of the aspirin story is, however, not over, and
      its possible value in a variety of conditions, including dementia and certain
      cancers, seems likely to ensure that it will long continue to play a remarkable
      part in clinical practice.

PMID- 11333460
TI  - Genetic and molecular mechanisms of pulmonary hypertension.
AB  - Pulmonary arterial hypertension frequently occurs secondary to common
      cardiopulmonary diseases, and more rarely as a primary condition. Observations in
      animals and man have suggested genetic influences underlying the susceptibility
      to pulmonary hypertension. A gene underlying many cases of familial and
      apparently sporadic cases of primary pulmonary hypertension has now been
      identified, and a genetic approach to hypoxia-induced pulmonary hypertension
      promises to reveal new insights into the unique nature of the pulmonary
      circulation. The exploration of potential candidate genes influencing
      susceptibility and the identification of new genes promise new therapeutic
      approaches to the treatment of pulmonary hypertension.

PMID- 11333461
TI  - HIV/AIDS: a commonwealth emergency; the challenge to medical education.

PMID- 11333462
TI  - Modern doctoring.

PMID- 11333463
TI  - Prevention and treatment of osteoporosis.

PMID- 11333464
TI  - Temporary cardiac pacing and the physicians of tomorrow.

PMID- 11333465
TI  - Bile acid malabsorption and post-infective diarrhoea.

PMID- 11333466
TI  - Understanding illness and medical humanities.

PMID- 11333467
TI  - Choices and conjoint twins: a personal view.

PMID- 11333468
TI  - Whither CPD? Let common sense prevail.

PMID- 11333469
TI  - Core knowledge in rheumatology: what does a general physician need to know?

PMID- 11333470
TI  - [Hyperglycemia in premature newborn infants].

PMID- 11333472
TI  - [Adrenal function in children with sepsis and septic shock].
AB  - OBJECTIVES: To assess adrenal function in children with sepsis and septic shock
      with petechiae and to investigate the possible relationship between adrenal
      hypofunction, sonographic diagnosis of massive bilateral adrenal hemorrhage, and
      other factors available early in this disturbance. PATIENTS AND METHODS:
      Prospective observational study of 24 patients (14 boys, 10 girls), aged 2.9.24
      years, admitted to the pediatric intensive care unit with sepsis and septic shock
      with petechiae during a 1.5-year period. The control group included 26 healthy
      children (13 boys, 13 girls), aged 8.8.6.4.2 years. Plasma cortisol and
      adrenocorticotropic hormone (ACTH) were measured by radioimmunoassay and adrenal
      ultrasonography was performed. RESULTS: Plasma cortisol and ACTH levels were
      243.7 ng/ml and 135.0 pg/ml in the patient group and 145.4 ng/ml and 21.1 pg/ml
      in the control group (p<0.01 in both). Adrenal insufficiency was found in four
      patients. Children with insufficiency more frequently required noradrenaline than
      did those with normal adrenal function (4/4 vs 2/20). Necrotic purpura (2/4 vs
      2/20), massive adrenal hemorrhage (2/3 vs 1/20), lower platelet count (69.500 vs
      212.895/l), lower prothrombin activity (19.0 vs 49.2%), lower fibrinogenemia
      (51.2 vs 304,4 mg/dl), higher pediatric risk of mortality III (PRISM III) scores
      (11.7 vs 2.7) and higher mortality rate (3/4 vs 1/20) were found in children with
      adrenal insufficiency than in those with normal adrenal function. CONCLUSIONS:
      Plasma cortisol and ACTH levels were increased in children with sepsis and septic
      shock. Adrenal insufficiency was uncommon. Adrenal insufficiency was associated
      with severe hemodynamic failure, necrotic purpura, disseminated intravascular
      coagulopathy, massive bilateral adrenal hemorrhage and high mortality rate.

PMID- 11333473
TI  - [Antiphospholipid antibodies in asymptomatic pediatric patients].
AB  - BACKGROUND: Findings of prolonged activated partial thromboplastin time (APTT)
      and lupus anticoagulant are rare in asymptomatic children and are often preceded
      by certain types of surgery. Clinical behaviour is usually favorable. PATIENTS
      AND METHODS: We assessed the biological and clinical features of antiphospholipid
      antibodies found in 13 children diagnosed between January 1996 and September 2000
      (mean age at diagnosis: 5 years). The patients were prospectively followed-up for
      a median of 16 months (range: 15-60). The diagnosis of lupus anticoagulant was
      based on the guidelines of the International Society of Thrombosis and Hematosis
      and included coagulation-based assays as well as enzyme-linked immunosorbent
      assay for anticardiolipin and anti-beta 2 glycoprotein I. RESULTS: In all
      patients lupus anticoagulant was detected after investigation of prolonged APTT
      prior to surgery (adenoidectomy in eight patients, orchidopexy in one and eye
      surgery in one). The antibody was associated with infectious mononucleosis in one
      patient and was detected during routine laboratory investigations in two. All
      antibodies were primary and 53.6% of events were transient. In all patients lupus
      anticoagulant IgG and anti-beta 2 glycoprotein I were negative. Slightly reduced
      factor XII:C plasma concentrations (mean: 38.2 UI/dl) were found in 30.7% of the
      patients. No clinical manifestations of antiphospholipid symptoms were associated
      with the diagnosis of antiphospholipid antibodies and none of the patients
      experienced bleeding after surgery. CONCLUSIONS: Primary antiphospholipid
      antibodies were infrequent in asymptomatic pediatric patients and were typically
      associated with certain types of surgery (adenoidectomy, tonsillectomy) or viral
      infections. They were usually transient and clinically irrelevant. These
      antibodies may be associated with slightly reduced plasma concentrations of
      factor XII and consequently a differential diagnosis with a mild factor XII
      deficiency should be considered.

PMID- 11333474
TI  - [Role of tumor necrosis factor-a, nitric oxide and markers of clinical
      progression in the nutritional status of children with vertically-acquired hiv
      1infection].
AB  - OBJECTIVE: To study the correlation between the immunologic and virologic markers
      of clinical progression and the nutritional status of children with vertically
      acquired HIV-1infection. MATERIAL AND METHODS: We performed an anthropometric
      study in 34 HIV-1infected children. T cell subpopulations were analyzed by flow
      cytometry. Viral load (VL) was quantified by a standard commercial molecular
      assay. Tumor necrosis factor (TNF-) and nitric oxide (NO) concentrations were
      quantified by enzyme immunoassay. RESULTS: Z-weight, Z-height, Z-Quetelet index,
      Z-tricipital pleat, Z-arm perimeter, Z-cephalic perimeter, and McLaren's
      nutritional index were negatively correlated with VL. These anthropometric
      parameters were positively correlated with the percentage of CD4T lymphocytes but
      the correlation between these parameters and VL was lower. HIV-1infected children
      with a VL> 5 log 10 showed higher TNF- and NO concentrations and lower
      anthropometric scores. TNF- and NO concentrations were significantly higher in
      HIV-1infected children with a VL>5 log 10 than in those with a VL<5 log 10. TNF-
      and NO concentrations were significantly lower in HIV-1infected children
      undergoing antiretroviral treatment than in untreated HIV-1infected children. TNF
      and NO concentrations were significantly higher in the HIV-1infected children
      than in the control group. CONCLUSIONS: Our data suggest an association between
      anthropometric characteristics indicating the nutritional status of HIV-1infected
      children and immunologic and virologic markers of clinical progression
      (percentage of CD 4T lymphocytes and VL). Moreover, TNF- and NO play a
      significant role in the nutritional status and neurological alterations of these
      children.

PMID- 11333475
TI  - [Study of renal function in infants diagnosed with renal pyelectasis in the first
      year of life].
AB  - OBJECTIVE: To evaluate glomerular and tubular function in a group of infants
      diagnosed with pyelectasis. PATIENTS AND METHODS: We studied 14 patients
      diagnosed with renal pelvis dilatation in-utero or during the first year of life.
      Creatinine concentrations, urinary excretion of calcium, citrate, oxalate, N
      acetyl-D-glucosaminidase (NAG), microalbumin and maximum urine osmolality after
      administration of intranasal desmopressin were determined. The latter three
      variables were determined at diagnosis and at the end of follow-up. RESULTS: In
      all patients creatinine levels were normal. In six patients (42.9%) maximum urine
      osmolality values were abnormal. In four patients NAG/creatinine concentrations
      were elevated and in another four patients (28.6%) albumin urinary excretion was
      elevated. These anomalies tended to return to normal but, at the end of the
      study, three patients (21.4%) showed increased albuminuria and one (7.1%) showed
      persistently defective renal concentrating capacity. Ten patients showed
      metabolic urinary anomalies, potentially leading to the formation of stones
      (isolated hypercalciuria in five [35,7%], hyperoxaluria in two and hypocitraturia
      in one, and hypercalciuria associated with hyperoxaluria in two). CONCLUSIONS:
      All patients showed normal glomerular function. Some patients presented increased
      albuminuria and moderate tubular function abnormalities, both of which tended to
      return to normal. Although studies with greater numbers of patients are needed,
      we propose that pyelectasis maybe a predictor of risk for lithiasis at later
      stages of life.

PMID- 11333476
TI  - [Long and medium-term neuropsychological sequelae of bone marrow transplantation
      in pediatric patients with hematological disease].
AB  - BACKGROUND: Few studies exist on the neuropsychological sequelae of bone marrow
      transplantation (BMT) in pediatric patients. Published results show considerable
      discrepancies although studies of children with acute lymphoblastic leukemia
      undergoing high doses of cranial radiotherapy report short- and long-term loss of
      cognitive ability. OBJECTIVES: To determine the effects of BMT and the effect of
      anxiety on the pre-BMT assessment in a group of children with severe
      hematological disease treated in our center. METHODS: We performed a descriptive,
      prospective, longitudinal study of 54 children, aged 4-15 years, who were treated
      between 1987 and 1995. Twenty-two children were evaluated before and after BMT by
      means of the Weschler Intelligence Scale. To control for the effect of anxiety on
      the pre-BMT scores, the patients were divided into two groups according to the
      scores obtained in this test (group 1: IQ score 100; group 1: IQ100). RESULTS:
      Comparison of pre- and post-BMT scores for both groups revealed no significant
      differences. However, comparison of the results between groups revealed that
      group I scored lower in the post-BMT test than in the pre-BMT test while group I
      scored higher in the post-BMT test than in the pre-BMT test. CONCLUSIONS:
      Although comparison between the pre- and post-BMT results obtained from the whole
      sample showed no differences that indicated post-treatment sequelae, treatment
      induced anxiety may have influenced the pre-BMT score.

PMID- 11333477
TI  - [Auxological study of contemporary and historical samples of the population of
      madrid].
AB  - OBJECTIVES: To describe statural growth in a sample of both sexes using the
      Preece-Baines model 1 (PB1) in order to obtain smoothed percentiles for use in
      reference growth charts. To apply the PB1to several historical samples, with
      different age ranges, obtained from the literature (1896-1983) in order to study
      secular changes in stature. MATERIAL AND METHODS: The sample consisted of 1,525
      schoolchildren, aged 6-18 years. The PB1was fitted to the percentile curves,
      which were corrected for deviation from normal distribution by the LMS model. The
      PB1was applied to the historical samples and the variables describing growth
      spurt and adult height were compared. RESULTS: The age of peak height velocity
      (PHV) was 13.73 years in males and 11.02 years in females. Estimated adult
      height, in this model, was 176.22 cm for males and 163.53 cm for females. Mean
      velocity of secular change in males was estimated as 1.2 cm/decade. The age at
      PHV increased by 0.2 years/decade. CONCLUSIONS: The PB1did not achieve smoothed
      percentile curves for use in reference growth charts. Right skewness of the
      distribution was corrected by application of the LMS method. However, the PB1is
      useful for studying secular trends in statural growth.

PMID- 11333478
TI  - [Melanocyte nevus in childhood].
AB  - Melanocytic nevi are due to benign melanocyte proliferation. Most melanocytic
      nevi develop during childhood and adolescence and give an stabilization in middle
      age (already 25 years old). About 1% of newborns presents congenital nevi.
      Removal of nevi is not usually required except in cases of giant congenital nevi
      and clinically atypical nevi. The aim of this study was to review the different
      types of nevi, their possible associations and prevention of risk factors. Sun
      exposure, atypical or numerous nevi, phenotypical risk of nevi and familial
      antecedents of melanoma are predisposing factors for melanoma. Epidemiological
      studies confirm an increasing epidemic of melanoma in adults and evidence exists
      that this worldwide epidemic is also affecting the teenage population.
      Pediatricians play an important role in the prevention and early diagnosis of
      these lesions. They can also educate parents and children on adequate sun
      screening, which includes the use of sunscreens against ultraviolet A and B
      radiation, the wearing of protective clothing and the avoidance of overexposure
      to sunlight.

PMID- 11333479
TI  - [Diets in pre-school, school and adolescent age groups. Special situations:
      vegetarian diets and physical exercise].

PMID- 11333480
TI  - [Persistent hyperglycemia and hyperinsulinemia in a newborn infant].
AB  - Management of neonatal hyperglycemia is complex, especially in immature newborns.
      Etiology is diverse, the most frequent cause being iatrogeny. Neonatal diabetes
      mellitus is a rare cause of hyperglycemia during the first days of life. Insulin
      treatment is sometimes required to control the condition. When insulin
      requirements exceed 2I U/kg/day insulin resistance syndrome should be suspected.
      We present the case of a newborn infant with Donohue syndrome, or leprechaunism,
      which is a rare, genetically determined dysmorphic syndrome leading to
      significant insulin resistance.

PMID- 11333481
TI  - [Permanent neonatal diabetes associated with other anomalies].
AB  - Neonatal diabetes mellitus is defined as hyperglycemia detected in the first
      month of life of more than 2 weeks' duration, requiring insulin treatment. It is
      extremely uncommon (1/500,000 neonates) and is permanent in only 30% of cases.
      Several hypotheses concerning its etiology have been postulated, such as
      pancreatic immaturity, paternal uniparental isidisomy of chromosome 6, and the
      existence of a gene located in the 6 q 22-23 chromosome region subjected to
      imprinting and exclusively of paternal expression. The management of these
      patients is usually difficult. These neonates are underweight for their
      gestational age, and neither anti-insulin antibodies nor anti-islets are
      detected. We studied a neonate hospitalized because of low weight for his
      gestational age with dimorphic features and hyperglycemia since the 17 th day of
      life. Clinical and anatomical follow-up has been periodically performed to the
      present date. The child presents permanent neonatal diabetes with negative
      antibodies. Although various insulin patterns have been used since the onset of
      the syndrome, management remains difficult. The child presents hypothyroidism,
      bilateral neurosensory deafness, bilateral congenital cataract, myopia, dimorphic
      features, congenital stridor and slow weight-stature curve. The results of muscle
      biopsy and metabolic studies were normal. Wolfram's syndrome and mitochondrial
      diabetes were ruled out. This is an exceptional case of permanent neonatal
      diabetes associated with other malformations corresponding to no known syndromic
      patterns.

PMID- 11333482
TI  - [Childhood cutaneous polyarteritis nodosa].
AB  - Cutaneous polyarteritis nodosa is a form of polyarteritis nodosa. It is a rare
      disease in children and is characterized by its benign and chronic course. There
      is no evidence of hypertension or organ dysfunction. The aim of this study was to
      present a case of cutaneous polyarteritis nodosa and to review the literature. We
      describe the case of a 3-year-old male child with multiple, red, painful,
      edematous nodules of the extremities and trunk. Dermatologic findings were
      accompanied by fever and arthritis. Laboratory findings showed an acute phase
      response associated with raised antistreptolysin titer. Diagnosis was based on
      biopsy of the affected skin lesion in which necrotizing arteritis of the lower
      dermis with neutrophilic and eosinophilic infiltrates was found. The patient
      responded well to corticosteroid therapy. The evaluation of children with
      cutaneous polyarteritis nodosa should include laboratory studies to detect
      streptococcal infection.

PMID- 11333483
TI  - [Reactive arthritis shortly after Streptococcus b-hemolyticus type A and
      Salmonella type B infection].
AB  - We report the case of a girl aged 2 years and 8 months with monoarticular
      arthritis of the knee. Onset and outcome were slow. The child had suffered
      uncomplicated pharyngitis and a diarrheal process 1 and 2 weeks respectively
      prior to developing the disease. Additional data suggested the presence of
      reactive arthritis after Streptococcus infection. Salmonella was also detected in
      the feces. Unlike rheumatic fever, post-streptococcus reactive arthritis does not
      follow Jones' criteria and the clinical course is slow. Because gastrointestinal
      infection with both Streptococcus and Salmonella occurred simultaneously, the
      interaction between both agents, each of which alone can cause reactive
      arthritis, might have produced a synergic action in our patient.

PMID- 11333484
TI  - [Primary ciliary dyskinesia. report of three cases].
AB  - Primary ciliary dyskinesia is an autosomal recessive disorder, characterized by
      total or partial dysfunction of the ciliary or flagellated cells. It is
      clinically expressed by sinusitis and/or bronchiectasis occasionally associated
      with sterility in males. We report three cases of immotile cilia syndrome with
      chronic respiratory symptoms (sinusitis, bronchitis, otitis). The syndrome was
      associated with bronchiectasis in two cases and by half lobe atelectasis in the
      third. Diagnosis was established by ultrastructural study of samples from the
      nasal mucosa, in which the absence of the dynein arms and/or the anomalous
      disposition of the microtubules was observed. In all three patients great
      clinical improvement and symptom control were achieved, thereby improving the
      prognosis of these children. Although the syndrome cannot be cured, as in other
      chronic pneumopathies, early diagnosis and appropriate treatment can considerably
      reduce morbidity.

PMID- 11333485
TI  - [Acute infectious lymphocytosis associated to Giardia lamblia and Blastocystis
      hominis coinfection].
AB  - Acute infectious lymphocytosis is characterized by marked peripheral blood
      lymphocytosis, often associated with a mild, nonspecific febrile illness. We
      present a 4-year-old girl with acute infectious lymphocytosis associated with
      Giardia lamblia and Blastocystis hominis coinfection. Analysis of peripheral
      lymphocyte markers showed overall proliferation of B and T cells with a reduction
      in the proportion of T cells, especially in the CD4T cell subpopulation.
      Hematologic values returned to normal after treatment with metronidazole.

PMID- 11333486
TI  - [Soft tissue cranial tumor].

PMID- 11333487
TI  - [Diagnostic yield of bacilloscopy and gastric juice culture in childhood
      tuberculosis].

PMID- 11333489
TI  - [Chemoprophylaxis of meningococcal disease with azithromycin and ciprofloxacin].

PMID- 11333491
TI  - [Reference values of interleukin-6 and tumor necrosis factor-alpha in healthy
      newborn infants].

PMID- 11333492
TI  - [Apropos of anti-reflux formulas].

PMID- 11333512
TI  - [Cognitive deficit and schizophrenia].
AB  - INTRODUCTION: In the present paper, the results of a number of different studies
      that have tried to establish the characteristics of the cognitive deficit in
      schizophrenia are discussed. The principal objective of this study was to
      ascertain whether exist statistically significative differences in such deficit
      in schizophrenic patients in relation with their preponderant symptomathology
      (positive symptoms, negative symptoms, and disorganization) or their degree of
      defectual symptoms. METHODOLOGY: Sixty three schizophrenic patients under
      treatment in a Day Hospital were divided in groups using the dimensions of Liddie
      and the Scale for assessing the Deficit Syndrome in Schizophrenia. Cognitive
      deficit was assessed by the Wisconsin Card Sorting Test (WCST). RESULTS: Our
      results show that education and gender has no relation with the cognitive deficit
      exhibited, whereas there is a direct relation with age and years suffering the
      illness. Patients who exhibited preponderant disorganization symptoms and those
      describes as defectual syndrome schizophrenics showed more cognitive deficit in
      the WCST. The number of preservations in the WCST seems to be the main deficit.
      CONCLUSIONS: The concept of planning in suggested as a schizophrenic marker in
      the frame of theories that claim there is a failure in the neurodevelopment of
      these patients.

PMID- 11333513
TI  - [Factors associated to the development of Posttraumatic Stress Disorder].
AB  - INTRODUCTION: Motor vehicle accidents appear to increase the risk of severe
      psychiatric morbidity in survivors. MATERIAL AND METHODS: We have studied
      retrospectively a population of 2,885 people who suffered an automobile accident
      in the city of Sabadell (Spain) in 1998. From these, we randomly selected a
      sample of fifty people who had developed PTSD, and a control group including the
      same amount of people. RESULTS: We reviewed the clinical and demographic
      differences in both samples and we found out that female gender and previous
      psychiatric morbidity are strongly related to the onset and course of PTSD.

PMID- 11333514
TI  - [Personality factors and psychiatry specialty attraction].
AB  - INTRODUCTION: In this article, we analyse the possible rapport between the
      determined trends of personality and the Psychiatry Specialty and we try
      determinate the existence of certain Profiles of Personality in the students who
      feel attracted by this specialty. MATERIAL AND METHOD: We analyse 1484 students
      of second year of Medicine Faculty's of the Valencia University (Spain). An
      anonymity interview about the sociodemographics characteristic and vocational
      interests of the students has done. We determinate their personality profile with
      the Test of personality 16 PF of Cattell. We analyse the dates with an t-Student
      Test. RESULTS AND CONCLUSIONS: The population analyses was of predominantly
      feminine (62.7%) and with an age medium of 20 years. The Psychiatry specialty was
      chose by the 8.06% of the students. These students tend be in reference with the
      another students sensitive, immature emotionally, insure. (I+) and unstable,
      impulsive, untidy (Q3-). The bibliographic revision tend to confirm this
      tendency.

PMID- 11333515
TI  - [Visuo-perceptual processing in patients with schizophrenia treated with typical
      or atypical antipsychotics].
AB  - OBJECTIVE: This is a pilot study exploring the possible association between a
      particular antipsychotic (AP) medication regime and both clinical and visuo
      perceptual features. SUBJECTS AND METHOD: A series of 32 patients (25 males; mean
      age+/- SD = 28.1+/- 5.1 years, range 20-39) suffering from schizophrenia for at
      least two years (mean+/- SD duration of illness = 6.0+/- 3.6 years), and
      maintained on the same antipsychotic medication for at least one year, were
      divided into four groups according to their maintenance medication. Their
      assessment included the Positive and Negative Syndrome Scale (PANSS), the Rey's
      Complex Figure test (visual perception and memory), and Leff's BELS scale (skills
      of daily living). RESULTS: There were not significant differences in demographic
      features or daily living skills. The patients on oral classical APs scored
      significantly higher on the disorganization factor than those on clozapine. In
      general, patients on atypical APs did better on the visual perception and memory
      tasks, with those on fluphenazine decanoate being the poorest. In the whole
      series of the 32 patients, the copy time increased with age, with higher scores
      on the negative and the depressive factors, and with lower scores in visual
      memory. On multiple linear regression, only visual memory score and age remained
      significant. CONCLUSIONS: In spite of the small sample size, patients on atypical
      APs seem to be in a better condition, both in symptoms and in visuo-spatial
      abilities. Visual reproduction is influenced by both visual memory and age.

PMID- 11333516
TI  - [Incidence of extrapyramidal symptoms during treatment with olanzapine,
      haloperidol and risperidone: results of an observational study].
AB  - OBJECTIVES: To analyze the incidence of extrapyramidal symptoms (EPS) and the
      concomitant use of anticholinergic drugs in outpatients diagnosed of
      schizophrenia treated with olanzapine (OLZ) in comparison with haloperidol (HAL)
      and risperidone (RIS) under routine clinical practice conditions. MATERIAL AND
      METHODS: The analysis was carried out on the basis of the information obtained in
      the EFESO study, an observational, prospective study carried out in outpatients
      diagnosed of schizophrenia and treated with olanzapine compared to other
      antipsychotic agents used in the clinical practice. The incidence of EPS in the
      OLZ treated group compared to the haloperidol and risperidone treatment groups in
      which over 100 patients were included is analyzed in the present work. The study
      duration was 6 months and the data were collected by 293 psychiatrists from
      mental health care areas. RESULTS: The percentage of patients who presented at
      least one adverse event (AE) (p 3/4 0.001) was less in the OLZ groups (47.8%)
      compared to those of the HAL (79.8%) and RIS (57.2%) subgroups. A lower
      percentage of patients treated with OLZ (36.9%) presented EPS in comparison to
      the RIS (49.6%) and HAL (76%) subgroups (p 3/4 0.001). A lower rate of patients
      from the OLZ group (10.2%) received anticholinergic treatments compared to the
      RIS (19.9%) and HAL (44%) subgroups (p< 0.001 in both cases). CONCLUSIONS: OLZ
      treated patients presented a lower incidence of EPS and required less
      anticholinergic treatment than the HAL and RIS treated patients. These results,
      obtained in naturalistic conditions, coincide with the conclusions reached in
      randomized clinical trials carried out prior to the marketing of OLZ.

PMID- 11333517
TI  - [Refusal of treatment].
AB  - The 25-50% of the outpatients who ask for medical assistance give up the
      treatment before the end for several reasons. The immediate consequences are the
      waste of economic and assistance resources, professional insatisfaction,
      phenomena like revolving door and bad results in prescribed treatments. These
      patients usually come back in the medium or long term. The authors considered to
      review the material published between 1992-1998 on the variables associated to
      the phenomena of noncompliance and dropout, as well as the strategies proposed by
      the different authors to face this problem. METHOD: A search was performed for
      original and review articles on the issue in the Medline database between 1992
      1997. The key words used were: dropout, appointments, schedules, non attendance,
      premature termination, non compliance, medication compliance and their links with
      the key words: psychiatry, psychotherapy and mental disorder. The bibliographic
      references were classified according to the type of article, author, country of
      origin, journal and year. In relation with the contents, one classification has
      been carried out according to approach strategies, and another according to
      variables associated to dropout and non compliance. RESULTS: 144 bibliographic
      references were identified after the search on the Medline database. The
      selection for revision included 24 original articles, 5 review articles and a
      letter to the editor as a comment to a previous article. The total number of
      different journals was 27, and the authors were from 6 different nationalities.

PMID- 11333518
TI  - [Antipsychotic treatment in childhood and adolescence: a bibliographical review].
AB  - The use of antipsychotic or neuroleptic drugs in childhood and adolescence is a
      controversal issue because of its ethical involvements and because of the
      difficult to fixing clinical guidelines. In this article, I'm looking over the
      literature about indications and adverse effects of these drugs. I'll specially
      insist in the new features of atypical neuroleptic drugs.

PMID- 11333519
TI  - [Sociocultural aspects of the genesis of personality disorders].
AB  - The prevalence of personality disorders seems to be increasing in the last
      decades. Many sociologists and historians believe that since the end of World War
      II, we have seen important changes, social, cultural and economic, which could
      indicate that we are entering a new age. The Postmodern Age, after nearly 500
      years of Modern Age. Postmodernits is characterized by an increase of the speed
      in all realms of life, permanent changes, materialism, dominance of capitalism as
      economic model, changes of roles, etc. We speculate about the posibility that the
      characteristics of postmodern society may be contributing to the increase of
      prevalence of personality disorders in general and some of them in particular.

PMID- 11333520
TI  - [Personality disorders and substance abuse disorders. Psychosocial strategies].
AB  - The article begin with a review of the high prevalence of concurrent mental
      illness and substance abuse disorders among general and clinical populations,
      highlighting the need for development of appropriate services to treat these
      persons. Several studies have revealed a significant adverse impact of comorbid
      personality disorders on treatment tenure and outcome in substance abuse
      populations and vice versa. We review findings on the longitudinal course of dual
      disorders in traditional treatment systems, which provide separate mental health
      and substance abuse programs, and describe new programs that integrate both types
      of treatment at the clinical level. This is followed by a description of main
      difficulties to do with outcome and treatment retention. Finally, we review the
      effectiveness of several specific treatments programs within psychiatric care for
      patients who have a dual diagnosis of a severe personality disorder and a
      substance abuse disorder. Such programs include, brief integrated programs based
      on the disease-and-recovery model or on the cognitive-behavioral model,
      comprehensive integrated assertive programs and intensive partial hospitalization
      programs. We conclude, that although several program features appear to be
      associated with effectiveness, there is no clear evidence supporting an advantage
      of any type of program when co-occurring substance abuse with severe personality
      disorder. Implementation of new specialized services for dual disorders should be
      within the context of simple, well designed controlled studies.

PMID- 11333521
TI  - [Clinical perspective in the folie a trois: a case report].
AB  - Induced psychotic disorder is infrequent. We report a case in which three members
      of the same family were affected. We analyzed certain etiological factors, family
      relationship and social and environmental conditions.

PMID- 11333522
TI  - [Capgras syndrome].
AB  - The authors report a case of Capgras' syndrome in a 16-years-old child, who had
      been hospitalized for psychotic disorder. A review of the literature is
      performed. Most authors state that Capgras' syndrome would represent a symptom of
      underlying medical o functional disorders, although the term syndrome is used.
      The main etiopathogenic hypothesis of this syndrome are put forward
      (psychodynamic, disconnection, neuropsychological and medical).

PMID- 11333524
TI  - [Prevalence of depressive disorders in consultation-liaison psychiatry].
AB  - INTRODUCTION: Depressive disorders are more frequently seen in medically ill
      patients, especially in those who are hospitalized, than in the general
      population. The aim of this study was to assess the magnitude of this problem in
      Spanish hospitals, determining the prevalence of depressive disorders in
      hospitalized patients with medical illnesses, as well as the sociodemographic and
      medical-psychiatric characteristics related with the development of depression in
      these patients. METHODOLOGY: A transversal study was performed in 13 Spanish
      public hospitals with a sample of 1.003 patients selected from the list of
      patients registered in medical services at each hospital on November 6, 1995.
      Each patient was evaluated on psycho-social stress level as well as quality of
      life (Karnofsky scale). Following that, the Hospital Anxiety and Depression Scale
      was applied and all patients with a score >= 11 were evaluated by a psychiatrist.
      Data on psychiatric consultation of these patients were also recorded when
      conducted. RESULTS: 18.9% of patients hospitalized for medical illnesses showed
      depressive symptoms. The presence of depressive disorders was more often seen in
      women, patients unable to work, patients with psychiatric history, patients with
      previous psychopharmacological treatments, patients with high level of
      psychosocial stress and patients with a low quality of life. Psychiatric
      consultations were requested in just 13.7% of these patients. CONCLUSION: A very
      high number of hospitalized patients require a psychiatric evaluation for
      depression, but this is not requested.

PMID- 11333525
TI  - [Olanzapine and cognitive-behavioural group therapy in borderline personality
      disorder].
AB  - INTRODUCTION: Borderline Personality Disorder (BPD) is considered one of the most
      difficult psychiatric conditions to treat, neither psychological nor
      pharmacological treatments have been shown to be particularly effective. We
      present a proposal for the treatment of patients diagnosed with BPD which uses an
      atypical neuroleptic, olanzapine, and cognitive-behavioural group therapy aimed
      at dealing with the following problems: Interpersonal Conflict, Affective
      Instability, Impulsiveness, and Confused Identity. METHODS: Six patients
      diagnosed with BPD using the International Personality Disorder Evaluation (IPDE)
      were treated during 6 months with olanzapine (at dosages of 5-20mg/day) and
      dialectical behaviour therapy, with weekly 2-hour sessions. RESULTS: All of these
      patients followed the programme during the first 2 months, and 3 of the 6
      completed it, showing an improvement in their behavioural disorder, as indicated
      by a decrease in parasuicidal episodes (i.e. suicide attempts and self-mutilative
      acts) and fewer visits to the emergency department. One of the patients dropped
      out due to side effects. DISCUSSION: The possibility of using a combined
      therapeutic approach enables us to project controlled clinical trials over a
      longer period of time, thus making it possible to assess behavioural changes
      which are difficult to observe in conventional clinical trials.

PMID- 11333526
TI  - [Anxiety and depression among renal transplantation candidates: impact of donor
      availability].
AB  - BACKGROUND: Among the kidney transplantation candidates, regardless if they
      already have a living related donor (LRD) or if they are waiting for a cadaveric
      donor (CD), the transplantation process is highly stressful, and the stress
      intensity is proportioned to the waiting time for surgery. The patients waiting
      for a CD have no certainty about receiving a kidney in time for surviving, or,
      when the patient's relatives refused the donation, they may feel rejected by
      their family. In chronic diseases, psychiatric comorbidity affects the disease
      evolution, dampering the treatment efficacy, leading to long-term
      hospitalizations and a more severe emotional stress. OBJECTIVE: To calculate the
      difference of anxiety and depression levels between LRD and CD patients. METHODS:
      The Hospital Anxiety and Depression scale (HAD) was applied to the kidney
      transplantation candidates who attended their first psychiatric evaluation along
      a year, they were grouped according to their kind of donor (LRD= 31, CD= 12).
      Statistical analysis was performed by means of Fisher and Mann-Whitney tests.
      RESULTS: 33.33% of the LRD patients were anxious (6.60+/- 2.65 points) and 40%
      were depressed (5.9+/- 3.29); 75% of the CD patients were anxious (p= 0.005)
      (10.17+/- 2.48, p< 0.001) and 90% were depressed (p= 0.088) (12.0+/- 9.33, p=
      0.005). CONCLUSIONS: The CD patients have a greater risk for anxiety and more
      severe depressive disorders than the LRD patients. Comparing this sample against
      100 patients with chronic diseases, we found no differences with CD patients, but
      they have a higher risk for anxiety and depression than LRD patients, this may
      suggest that the last mentioned patients may overestimate the prognosis of their
      disease.

PMID- 11333527
TI  - [Factorial variance of the SCL-90-R in a Spanish out-patient psychiatric sample].
AB  - OBJECTIVE: To test the consistency of the proposed structure for the SCL-90R.
      METHOD: 598 first appointments of a Mental Health Centre were evaluated. 352 of
      these patients completed the SCL-90-R during their first appointment and also 6
      and 12 months later. The structure of this questionnaire from the first
      appointment as well as from follow-up observations is analysed separately in men
      and women by exploratory factor analysis. Moreover, confirmatory factor analysis
      have been applied in order to compare the relative adjustment with the data
      observed during the first appointment in the original model of Derogatis et al.,
      as well as in 3 other factor models. RESULTS: Exploratory factor analysis
      rendered a different factor structure with all other contrasted models, that were
      rejected by confirmatory factor analysis as well, in men and women. Only a
      relative temporal stability in factor structure, different for men and women, was
      found. CONCLUSION: It seems that this tool may be rather more useful as a unitary
      measure for global distress. In addition, our results suggest that the factor
      structure of the SCL-90-R may vary in the same sample depending on the gender and
      also possibly varying throughout the time of observation. According to this, the
      benefit of the SCL-90-R for descriptive and monitoring studies throughout the
      time is questionable for this type of samples.

PMID- 11333528
TI  - [Insight and use of health resources in patients with schizophrenia].
AB  - INTRODUCTION: The objective of this work is to study the insight level of
      patients with schizophrenia and how the insight is related to sociodemographic,
      clinical and compliance variables. Besides, we evaluated the influence of insight
      level in the utilization services. PATIENTS AND METHODS: Sixty nine patients
      meeting schizophrenia criteria were selected. They were evaluated with a
      sociodemographic questionnaire, clinical and social adjustament scales (SCAN,
      GAF, PANSS, DAS), a services and cost questionnaire (CECE) and the insight scale
      of Amador (SUMD). RESULTS: The results were that gender, degree of education,
      type of residence and some clinical and disability variables were related to
      insight level. On the other hand, patients with a lower insight level attented
      more to emergencies and less to mental health centers. CONCLUSION: Insight level
      is an important determinant of adequate health service use in schizophrenia.

PMID- 11333529
TI  - [Decline in the diagnosis of schizophrenia in the last decades].
AB  - Important declines in the diagnosis of schizophrenia have been demonstrated in
      different countries and continents over the past few decades. Is still not clear
      if this findings reflects a true decrease in the incidence or is simply an
      artefact. The administrative rates are influenced by factors such as changes in
      the illness behavior of the patients, changes in diagnostic habits,
      administrative inaccuracies, changes in the organisation and delivery of
      psychiatric services, or changes the underlying pupulation structure.

PMID- 11333530
TI  - [Epileptic psychosis: the neuropsychiatric bridge].
AB  - The aim of this work is the review of the relationship between epilepsy and
      psychosis, considering the historic evolution, the classification, the treatment
      and the present situation of the ethiological aspects. Pointing up interictal and
      postictal psychosis due to their ethiological interest.

PMID- 11333531
TI  - [Treatment of schizophrenia in subjects with substance use disorders: A review].
AB  - BACKGROUND: Schizophrenic patients have a high comorbidity with substance use
      disorders. However, there are few studies on the efficacy of antipsychotics on
      psychopathology and on their repercutions on substance abuse. METHODS: All
      studies about pharmacological treatment of schizophrenic patients with substance
      abuse, included in Medline over the last ten years were analyzed. RESULTS: Of the
      17 studies reviewed, most were prospective with small samples (< 30 patients, 5
      studies) or case reports (7 studies). Objectives were to assess the efficacy on
      schizophrenic symptoms and the effect of the treatment on substance use. Atypical
      antipsychotics were the most studied. These pharmacological agents were effective
      at reducing symptoms and had few side effects. They also managed lo reduce
      substance abuse in 66-75% of patients. CONCLUSIONS: In spite of underlyng
      methodological problems of these studies, the findings suggest that atypical
      antipsychatics could be the treatment of choice in these patients.

PMID- 11333532
TI  - [Genetic dysfunction of the serotonin receptor 5-HT2A in psychiatric disorders].
AB  - So far, there is increasing evidence of the active role of molecular biology in
      the psychiatric nosology as well as in the identification of psychiatric
      fenotypes. In this respect, the neurotransmitter serotonin (5-HT) has been
      involved in the etiopathogeny of multiple psychiatry conditions, such as
      affective disorder, schizophrenia, panic disorder, obsessive-compulsive disorder,
      alcoholism, eating disorder and personality disorder. The 5-HT2 receptor family
      includes the subtype 5-HT2A, a G protein coupled receptor whose activation leads
      to the stimulation of the enzyme phospholipase C and to the subsequent hydrolysis
      of the membrane located phosphoinositides, with the synthesis of the second
      messengers inositol triphosphate and diacylglicerol. This paper includes a review
      of the main findings concerning the polymorphism of the 5-HT2A in psychiatric
      disorders.

PMID- 11333533
TI  - [Craniopharyngioma and eating disorders: report of two cases].
AB  - Two patients are described in whom surgical removal of craniopharyngioma was
      followed by severe hyperphagia and morbid obesity. Similarities and differences
      are analysed, consequences for outcome of surgery and prognosis. Some biological
      ethiological factors implied in hyperphagia are commented and their relationship
      with bulimia are reviewed.

PMID- 11333534
TI  - [Good news about pulmonary hypertension].

PMID- 11333535
TI  - [Metabolic activity of the external intercostal muscle of patients with COPD].
AB  - INTRODUCTION: The external intercostal muscle is a relevant contributor to
      ventilatory work in situations of overloading. Like other respiratory muscles,
      the external intercostal muscle seems to undergo a process of structural
      remodeling to adapt to a situation of functional disadvantage. However, findings
      from published studies of morphology have differed to a certain degree. On the
      one hand, the proportion of fibers involved in anaerobic metabolism increases; on
      the other hand, the number of capillaries also increases, an occurrence that
      would facilitate aerobic metabolism. OBJECTIVE: This study was designed to
      analyze the activity of several key enzymes involved in the principal metabolic
      pathways in the external intercostal muscles of patients with COPD. METHODOLOGY:
      We studied 6 patients with COPD (65 +/- 8 years, BMI 23 +/- 3 kg/m2, FEV1 51 +/-
      9% ref, RV 184 +/- 38% ref, PaO2 81 +/- 10 mmHg) and 6 control subjects matched
      for age and anthropometric variables but with normal lung function. External
      intercostal muscle samples were taken from each patient (fifth intercostal space,
      non-dominant side). The samples were treated by conventional spectrophotometry to
      determine enzyme activity as follows: citrate synthase (CS, Krebs cycle),
      phosphofructokinase (PFK, by common glycolysis), lactate dehydrogenase (LDH,
      anaerobic glycolysis) and creatine phosphokinase (CPK, use of energy reserves).
      RESULTS: Patients with COPD showed greater PFK enzyme activity (93 +/- 25 versus
      44 +/- 9 micromol/min/g of fresh weight; p = 0.001) and LDH (308 +/- 42 versus
      231 +/- 29 micromol/min/g; p < 0.01) than did control subjects. However, CS and
      CPK activity was similar in both groups (82 +/- 31 versus 90 +/- 20
      micromol/min/g and 4017 +/- 1734 versus 3048 +/- 464 micromol/min/g,
      respectively), although the latter displayed noteworthy dispersion of values
      among COPD patients, with levels in some patients being three-fold greater than
      in controls. RV was directly related to glycolytic enzyme activity (with PFK, r =
      0.716, p < 0.01; with LDH r = 0.697, p < 0.05) and PFK and LDH also correlated
      with each other (r = 0.737, p < 0.01). CONCLUSIONS: Based on the enzyme activity
      studied, oxidative activity seems to be conserved in the external intercostal
      muscle of patients with COPD. Activity in the glycolytic pathway seems to
      increase and the increase is proportional to the severity of COPD. These findings
      are probably the expression of a combination of adaptive structural factors.

PMID- 11333536
TI  - [The self-efficacy of school principals and their influence on smoking prevention
      at school].
AB  - INTRODUCTION: Self-efficacy is a psychological variable that has scarcely been
      taken into account in approaches to smoking prevention among young people. The
      self-efficacy of school principals may play a role in schools that truly comply
      with their mission of preventing or limiting the influence of smoking among
      students. OBJECTIVE: To know the degree to which self-efficacy of school
      principals influences behavior toward smoking in their schools, assessed as
      attitude of students toward smoking, the degree of compliance with official anti
      smoking laws and the content of anti-smoking campaigns undertaken. MATERIAL AND
      METHODS: A questionnaire was designed and sent to 3050 school principals to
      assess their level of self-efficacy in reducing the percentage of smoking
      students, the behavior of students and teachers with regard to smoking, the
      degree of compliance at school with anti-smoking laws and the content of anti
      smoking campaigns undertaken. The data were codified and analyzed using
      appropriate statistical tests for each type of variable. RESULTS: Mean self
      efficacy scores of the school principals for reducing the prevalence of smoking
      in their centers was 38.7 (SD 30.86) points on a scale of 100. The score was
      40.18 (SD 30.8) where anti-smoking campaigns were undertaken and 34.31 (SD 30.43)
      where they were not. The mean score was 40.09 (SD 30.8) where anti-smoking
      posters were visible and 36.68 (SD 30.75) where no posters were hung(p < 0.05).
      The mean score of centers whose principals reported requiring compliance with
      anti-smoking laws was 39.78 (SD 30.8) and for schools where the law was not
      followed the score was 36.12 (SD 30.9) (p < 0.05). CONCLUSIONS: Schools whose
      principals have higher levels of self-efficacy display better general levels of
      functioning and a higher level of compliance with law and anti-smoking curricula.
      It seems necessary to direct efforts toward strategies to improve principals'
      self-efficacy for the prevention of smoking.

PMID- 11333537
TI  - [Surgical treatment of non-small cell lung cancer with mediastinal node invasion.
      A retrospective study].
AB  - OBJECTIVE: To analyze the survival of patients classified as N2M0 (N2 by
      cytohistology) with non-small cell lung cancer treated by surgical resection of
      the primary tumor and lymphadenectomy. PATIENTS AND METHODS: Among 1043
      consecutive patients with lung cancer who were considered for surgery between
      1990 and 2000, 155 were classified N2M0 by histology. Surgical exeresis of the
      primarily pulmonary tumor and lymphadenectomy were performed in 116 patients of
      the 130 patients who underwent thoracotomy. Among the 116 N2M0 patients
      undergoing surgical resection, 23 were diagnosed N2c(C3) by mediastinoscopy
      and/or mediastinotomy and were given induction chemotherapy (ChT)
      (mitomycin/ifosfami-de/cisplatin, 3 cycles) and 93 were diagnosed N2pM0 based on
      samples obtained from mediastinal lymph tissue during thoracotomy. Nineteen of
      the latter had previously been classified negative during surgical exploration.
      The patients diagnosed N2p after thoracotomy were given adjuvant ChT,
      radiotherapy or both. N2p patients who received induction therapy were given
      radiotherapy. Those found negative after lymphadenectomy and patients with severe
      disease were given no adjuvant treatment. RESULTS: Mean survival was 18 months
      for resected patients diagnosed N2 by mediastinoscopy/mediastinotomy and with
      induction ChT and survival at one, two and five years was 80%, 45% and 30%,
      respectively. No postoperative mortality was recorded in this group. One patient
      suffered bronchopleural fistula. Nine patients showed no residual mediastinal
      node disease after lymphadenectomy. The mean survival of resected patients
      diagnosed N2p by thoracotomy was 13 months, and one, two and five year survival
      rates were 56%, 31% and 19%, respectively. Fourteen patients died within 30 days
      of surgery. Nine patients developed a bronchopleural fistula. The difference in
      survival of the two groups was not significant. CONCLUSIONS: The prognosis after
      cytohistologic confirmation of N2 disease can be considered poor. Standard,
      complete surgery plus induction therapy in screened patients improved survival
      for those diagnosed N2 by thoracotomy, with no statistically significant
      differences.

PMID- 11333538
TI  - [The physician and the patient in the decision to quit smoking. Effect of the
      initiative on the result of the intervention].
AB  - INTRODUCTION: The results obtained from treatment of smoking addiction are not
      all that might be desired, such that continued investigation of the various
      factors that determine treatment success or failure are necessary. The aim of
      this study was to know the influence of health care providers in the smoking
      cessation process. MATERIAL AND METHODS: We performed a prospective, longitudinal
      study of patients at a primary care facility and a specialized unit. Two types of
      intervention were performed: minimal intervention with patients with a low level
      of dependence and nicotine patch substitution treatment (Nicotinell) (NST) in
      patients with moderate-to-high dependence. RESULTS: The total number of smokers
      enrolled was 427: 206 at the primary care facility (87 who requested treatment
      and 119 to whom enrollment was recommended) and 21 at the respiratory medicine
      unit (79 who requested treatment and 142 to whom enrollment was recommended). One
      year after minimal intervention, abstinence was 36.8% (27.2%-47.4%) at the
      primary care center and 41.8% (31.9%-52.2%) at the specialized unit (p > 0.05).
      Abstinence in the NST group at each center was 35.3% (24.1%-47.8%) and 35.5%
      (25.8%-46.1%), respectively (p > 0.05). With minimal intervention, 40% (16.3%
      67.7%) of those who had requested enrollment had quit smoking one year after
      starting, versus 36.3% (32.1%-46.9%) of those to whom it had been recommended (p
      > 0.05); in the NST group, the percentages were 33.3% (24.4%-43.2%) and 39.3%
      (26.5%-53.2%) (p > 0.05). The percentage of abstinence among smokers in pre
      contemplation phase was 28.4% (18.5%-40.1%) one year after starting; among those
      in the contemplation phase, abstinence at one year was 49.2% (36.6%-61.9%) (p <
      0.05). The patients whose enrollment was the result of physician recommendation
      had better outcomes (odds ratio of 0.244 [95% CI: 0.097-0.616]). CONCLUSIONS:
      Intervention among smokers should be as strong among those who ask for help as
      among those who have not yet contemplated quitting; progress to another phase in
      the abandonment process, so that efforts to achieve total cessation can be
      approached at a later time, should be considered a therapeutic success.

PMID- 11333539
TI  - [The role of peripheral muscles on exercise tolerance in patients with COPD].

PMID- 11333540
TI  - [Guidelines for domiciliary mechanical ventilation. Working Group on Home
      Mechanical Ventilation].

PMID- 11333541
TI  - [Bronchial carcinoid tumor: diagnosis by fiberoptic bronchoscopy].

PMID- 11333542
TI  - [Do primary care physicians really treat superimposed infections well in the
      context of COPD?].

PMID- 11333544
TI  - [Osteoarticular tuberculosis of the right shoulder].

PMID- 11333545
TI  - [Bronchodilator testing in patients with stable COPD].

PMID- 11333546
TI  - [Chylothorax complicating Waldenstrom macroglobulinemia].

PMID- 11333547
TI  - [Ten minutes, less!].

PMID- 11333548
TI  - [Accuracy and precision in blood pressure measurement. Comparative study of home
      self-measurement with measurement in the clinic and out-patient monitoring].
AB  - OBJECTIVE: To compare accuracy and precision of self-measurement blood pressure
      (SMBP) at home, as a diagnosis method of hypertension, with mercury measurement
      in office and ambulatory blood pressure monitoring (ABPM). DESIGN: A comparison
      study of diagnosis methods.Setting.Hypertension Unit in the Hospital General de
      Albacete. PATIENTS: By means of a non-probabilistic sample, selected from
      consecutive cases that went to the unit, a 64 pharmacologically untreated
      hypertensive sample older than 18 has been selected. METHODS: All subjects were
      taken 3 measurements with mercury from a validated nurse in office, and were also
      taught to make 20 self-measurements of blood pressure in the morning at the
      office and 20 self-measurements in the evening at home with an automatic device
      Omron 705-CP, during the same day they were set a Takeda TM-2420 device
      programmed to measure their blood pressure for 24 hours. All proceedings were
      repeated 4 weeks later. Mean blood pressure values have been compared with every
      diagnosis method and sensitivity, specificity, positive and negative predictive
      value have been studied in every method reproducibility in every method has been
      analyzed. RESULTS: Subjects were 29 men and 35 women with a mean of 53 years old.
      The mean values of office blood pressure (OBP) have been higher than SMBP and
      ABPM in the two periods of the study. SMBP has had a higher specificity and
      predictive value than OBP. Reproducibility of repeated SMBP in standardized
      conditions is similar to ABPM. CONCLUSIONS: With a minimum program self
      measurements at home, in standardized conditions, they can be considered as an
      accurate technique in the diagnosis of hypertension.

PMID- 11333549
TI  - [Validity of an indicator of the quality of pharmacological prescription in
      patients with hyperlipemia].
AB  - OBJECTIVES: The computer system for billing prescriptions (SIFAR in Spanish)
      enables indicators to be extracted for the study and follow-up of the use of
      medicines in the INSALUD primary care areas. Concretely, we studied the indicator
      referring to pensioners consumption of lipid-lowering drugs (PCLL), not
      validated, and whose value is expected to drop as quality increases. The
      objective was to calculate the correlation of the indicator of prescription of
      lipid-lowering drugs on the SIFAR with the proportion of lipid-lowerers
      prescribed correctly for pensioners (PCP). DESIGN: A descriptive study of
      correlation between two indicators of drug prescription. SETTING: Four health
      districts in Madrid. PARTICIPANTS: The prescriptions of 49 general practitioners,
      chosen at random on the basis of three strata defined by the value of the
      indicator, were studied. Each doctor filled out a protocol of data for each
      pensioner patient to whom he/she prescribed a lipid-lowerer during the study
      period. MEASUREMENTS AND MAIN RESULTS: The PCLL and PCP indicators were compared
      through the correlation of Spearman. 6,779 prescriptions for 1,125 patients were
      collected from the 49 participating doctors. The mean percentage of lipid
      lowerers correctly prescribed was 31.9%, figure that rose to 77.5% when the LDL
      value was not specified. The correlation between the PCLL and the PCP was near
      zero. CONCLUSIONS: The PCLL indicator of the SIFAR does not discriminate quality
      in lipid-lowering drug prescription to people over 64.

PMID- 11333550
TI  - [Prevalence and factors associated with burnout in a health area].
AB  - OBJECTIVES: The main objective was to determine the prevalence of the burnout
      syndrome among health workers and its distribution by social, demographic and
      work variables. The secondary aim was to detect potentially modifiable causes.
      DESIGN: Descriptive cross-sectional study. SETTING: Primary care. PARTICIPANTS:
      All the 354 doctors, nurses and clinical auxiliaries belonging to the 22 primary
      care teams of Area VI, Madrid. MEASUREMENTS AND MAIN RESULTS: A self
      administered, anonymous questionnaire was sent out by internal mail. This had
      three instruments: a questionnaire on social and demographic variables, the
      validated questionnaire known as the Maslach Burnout Inventory and an open
      opinion section. High levels of burnout were detected: 30.6% in the high range on
      the emotional tiredness sub-scale, with higher scores among men (p = 0.026).
      There were also more paediatric staff affected in personal achievements. There
      was scant relationship of the syndrome to social variables. 43.9% thought they
      suffered or had suffered from some kind of physical or psychological disorder
      directly related to exercising their profession. 38.3% associated directly their
      burnout with the excess demand habitually experienced in clinics. CONCLUSIONS: We
      detected worryingly high levels of this syndrome among our professionals, similar
      to other surveys in Spain. The subjects of the survey linked their unease with
      certain work factors that could easily be modified. The training received in
      techniques of self-control and stress management is clearly insufficient.

PMID- 11333551
TI  - [Mortality attributable to alcohol in Catalonia and its provinces].
AB  - OBJECTIVES: To calculate the contribution of alcohol consumption to mortality in
      Catalonia in 1997, and its impact on premature mortality. To evaluate whether
      inter-provincial differences exist. DESIGN: Descriptive ecological study.
      SETTING: Catalonia. PATIENTS: Deaths of residents of Catalonia in 1997 for a
      cause related to excess alcohol consumption. MEASUREMENTS AND MAIN RESULTS: The
      data on the causes of death in Catalonia in 1997 were provided by the Catalonia
      Death Register. The population fractions attributable to alcohol used were those
      recommended by the United States Centers for Disease Control in 1987. Mortality
      attributable to alcohol and the potential years of life lost were calculated for
      Catalonia as a whole and province by province. 4.8% of mortality in Catalonia in
      1997 was related to excessive alcohol consumption. Mortality was higher in men
      (6.0%) than in women (3.5%). By diagnostic groups, malignant neoplasms (29.9%)
      contributed to the greatest number of deaths attributable to alcohol, whereas non
      intentional accidents was the greatest cause of premature death (50.9%). As a
      specific cause, the greatest number of potential years of life lost was due to
      motor vehicle accidents. The highest mortality rate due to alcohol in non
      intentional accidents and the lowest risk of death from digestive diseases were
      in all the provinces rather than in Barcelona. CONCLUSION: This study highlighted
      the importance of alcohol in the mortality figures, its contribution to premature
      death and the existence of major differences depending on the province of
      residence, especially in non-intentional accidents.

PMID- 11333552
TI  - [Family medicine: the Cinderella of undergraduate studies? Study of the views of
      medical students about the speciality of family and community medicine].
AB  - OBJECTIVE: To find the views of students doing the last year of medicine on the
      specialty of family and community medicine (FCM). DESIGN: Cross-sectional study
      through self-administered questionnaire. SETTING: Medical faculties of the
      Universities of Oviedo and Cantabria. PARTICIPANTS: Sixth-year medical students
      with possibilities of completing their degrees in the year 2000.Interventions. 22
      question multiple-choice questionnaire, including assessment of undergraduate FCM
      training and view of its inclusion as a subject, choice of specialty in the next
      residents (MIR) exam, status of FCM, choice of professional to treat common
      pathologies in primary care, and knowledge of an activity (management of short
      term time off) of GPs. MAIN RESULTS: 73% of the 94 medical students polled had no
      theoretical training in FCM, but 89% were in favour of including it in the degree
      programme. 6% wanted to work as GPs. 77% thought that the status of FCM was
      comparable to that of other specialties. The rest thought it was inferior,
      although its status would rise for half of these if the FCM residency lasted 4
      years. 50% would not choose FM to treat common pathologies in primary care. 55%
      identified the GP as the person empowered to issue sick notes for common illness.
      CONCLUSIONS: Lack of undergraduate training in FCM is the cause of lack of
      interest in this specialty among medical students, its lack of status and
      students' lack of knowledge.

PMID- 11333553
TI  - [Domestic violence: prevalence of suspected ill treatment of the elderly].
AB  - OBJECTIVE: To determine the prevalence of suspected ill treatment of the elderly
      (ITE) in the population cared for in a health district and to analyse the
      associated variables. DESIGN: Cross-sectional study.Setting. Les Planes (Sant
      Joan Despi, Barcelona). Urban Health District. PATIENTS: 307 patients over 70
      years old seen in the Health District. The study had 39 losses, 31 exclusions
      because of cognitive disorder and 18 because it was impossible to hold the
      interview. 219 completed the study. MEASUREMENTS AND RESULTS: The Pfeiffer test
      was administered through an interview, social and demographic variables were
      collected, a questionnaire on ill treatment was filled in (a positive reply was
      considered ITE), and physical dependence was evaluated (Katz index). Prevalence
      of ITE was 26 people or 11.9% (95% CI, 7.6-16.2), breaking down into 6 physically
      ill-treated, 20 psychologically, one sexually, 3 by negligence and 3 by neglect.
      Nine people suffered more than one kind of ill treatment. Significant associated
      variables were: being a woman 18% (p < 0.01), receiving social assistance 46% (p
      < 0.001), being a widow/widower 21% (p < 0.01), not having had paid employment
      20% (p < 0.04) and having a rotating residence 28% (p < 0.003). On application of
      multivariate analysis, being a woman (OR 4.99) and receiving social assistance
      (OR 7.55) maintained their significance. The presumed perpetrators were
      son/daughter (57%), spouse (8%), son/daughter-in-law (23%). 19% of these were
      drug-dependent and 15% suffered psychiatric disorders. CONCLUSIONS: The high
      prevalence of ITE is clear. These results should alert doctors to a previously
      under-rated health problem.

PMID- 11333554
TI  - [Economic impact of the introduction of a minor surgery program in primary care].
AB  - OBJECTIVE: To value the economic impact of implantation (establishment) of a
      minor surgery programme within health area of primary care in Albacete (Spain).
      SETTING: Primary care (PC). DESIGN: Observational, cross-sectional and
      retrospective study. Interventions and measurements. It has been recorded some
      patients operated on subsidiary minor surgery pathologies in the three health
      centers of Albacete area that participated in pilot experience from 1 November
      1997 to 30 October 1998. It has been calculated the fixed costs corresponding to
      sanitary staff and the repayment of chirurgical area daily. As well, it were
      calculated the costs corresponding to disposable and not disposable equipment. It
      were analysed costs in function of intervention and the total cost were compared
      with the cost it would have supposed if it would carried out in specialized
      private centers according to up to dated fees of 1998 insurance companies. MAIN
      RESULTS: During the study interval were operated on 185 patients with an average
      age of 64,5 years (SD +/- 21,4) with a slight predominance of women. All
      pathologies treated were benign, 39 cases were abscess, 38 were nail pathology,
      and 35 were foreign bodies removed.Cost were calculated on the basis of time of
      one year. Total cost of minor surgery programme were 1.234.440 Pts (7715 Euros)
      whereas if it would have carried out at specialized level it supposed between
      2621450 Pts (15755.23 Euros) and 4440000 Pts (26684.94 Euros). CONCLUSION: In our
      study, the minor surgery programme in primary care diminish the cost in
      comparison with private specialized level, at the same time as reducing standby
      list in specialities like surgery or dermatology.

PMID- 11333555
TI  - [Is the portfolio of services a useful instrument for allocating pharmaceutical
      resources in primary care?].
AB  - OBJECTIVE: To find whether in certain primary care teams an association exists
      between the level of coverage in determined services and expenditure on drugs for
      pathologies included in these services. DESIGN: Retrospective descriptive study.
      SETTING: Primary care, INSALUD, Area 1, Huesca. MEASUREMENTS AND MAIN RESULTS:
      Using the data on coverage of the service portfolio in 1999 and pharmacy
      expenditure by therapeutic sub-groups during January-October of the same year,
      the following was analysed:- The service caring for chronic patients:
      Hypercholesterolaemia and comparison with expenditure in sub-group B04A (lipid
      lowerers/ anti-atheroma drugs).- The service caring for chronic patients:
      Diabetes and comparison with expenditure in sub-groups A10A (insulin) and A10B
      (oral antidiabetic drugs). Expenditure was expressed as cost adjusted per 100
      insured persons, using the INSALUD coefficients for the adjustment (active person
      coefficient: 0.732; pensioner coefficient: 0.268). The relationship between the
      two variables was represented graphically by a cloud of dots. Association between
      them was measured by Pearson's correlation coefficient. No statistically
      significant correlation was found between coverage and pharmacy expenditure in
      these sub-groups. Hypercholesterolaemia/lipid-lowerers: Pearson's coefficient =
      0.334, 95% CI (-0.115 to 0.669). Diabetes/oral diabetic drugs and insulin:
      Pearson's coefficient < 0.1. CONCLUSIONS: The differences in coverage of the
      services analysed bear no direct relationship to pharmacy expenditure. The
      portfolio of services is not a good method of allocation of pharmaceutical
      resources.

PMID- 11333556
TI  - [Agendas to be enjoyed. 10 minutes per patient in flexible agendas].

PMID- 11333557
TI  - [Home pages for primary care].

PMID- 11333559
TI  - [Do we take care of glaucoma from primary care?].

PMID- 11333558
TI  - [The COMBO project. Criteria and guidelines for combined therapy of type 2
      diabetes. Consensus document (and II)].

PMID- 11333560
TI  - [What does olanzapine give us?].

PMID- 11333561
TI  - [After levonorgestrel, will mifepristone (RU486) be the next day-after pill?].

PMID- 11333563
TI  - [Is an adequate control of tuberculosis important?].

PMID- 11333562
TI  - [Neisseria gonorrhoeae infection in an area of Madrid: 1997-1999].

PMID- 11333564
TI  - [Hypertransaminasemia: the most frequent is more frequent than the infrequent].

PMID- 11333566
TI  - [Is rapid and specific virological detection of influenza really necessary?].

PMID- 11333567
TI  - [Helicobacter pylori infections: antigen detection in stool samples].
AB  - BACKGROUND: The aim of this study is to evaluate a new diagnostic test to detect
      Helicobacter pylori antigen in stool samples (HpSA), and compare the results with
      those obtained by standard techniques (rapid urease test,culture, histological
      examination of gastric biopsy specimens,13C-urea breath test and serology), in a
      paediatric population with gastrointestinal symptomatology. PATIENTS AND METHODS:
      Sixty patients with dyspeptic symptoms (37 females and 23 males;mean age 10.9
      years) attending the Gastroenterology Service were included in the study.
      Exclusion criterium was previous treatment with proton pump inhibitors, bismuth
      compounds or antibiotics. Rapid urease test, culture and histologic study of
      gastric biopsies,13C-urea breath test and serology, as well as HpSA, were
      performed to all patients. RESULTS: Forty seven patients were considered infected
      by H.pylori on the basis of bacterium isolation and 13C-urea breath test
      positivity. HpSAwas detected in 45 of the 47 H.pylori positive patients(95.7%).
      There were no HpSA false positive. CONCLUSION: Our results show that this new
      test is highly sensitive (95%) and specific(100%) for detection of H. pylori
      infection. It has some advantages over other non invasive techniques: it is easy
      to perform,requires no blood samples and its cost is lower than that of 13C-urea
      breath test.

PMID- 11333568
TI  - [Clinical evaluation of the Amplified Mycobacterium Tuberculosis Direct 2 test].
AB  - OBJECTIVE: To evaluate the performance of the Amplified Mycobacterium
      tuberculosis Direct Test 2- Gen Probe (AMTD- 2) for direct detection of
      Mycobacterium tuberculosis in smear-negative samples. PATIENTS AND METHODS: From
      January to December 1999, 683 specimens, 333 respiratory and 350 non-respiratory
      ones collected from 457 patients, were included in the study. All the samples of
      HIV-positive patients, the respiratory samples from patients suspected of having
      pulmonary tuberculosis (at least two by patient) and all non-respiratory samples
      were included. As diagnosis method of reference, the culture isolation was
      considered. Clinical data were analyzed in case of discrepant results and
      clinical diagnosis was considered the reference criteria. The technique was
      performed once a week. RESULTS: The sensitivity, specificity, and positive and
      negative predictive values of this assay were 58.9%, 93.9%, 37.1% and 97.4%
      respectively related to the standard culture. When referred to clinical diagnosis
      of active tuberculosis, these values improved to 70.4%, 97.7%, 73.1% and 96.8%
      respectively (in respiratory samples were 67.6%, 98.6%, 86.2% and 95.9% and in
      nonrespiratory ones 76.5%, 96.9%, 56.5% and 98.7% respectively). The mean time of
      diagnosis by culture and by AMTD-2 were 20.3 days (range 10-63) and 5.7 days
      (range 2-20) respectively. DISCUSSION: It is concluded that AMTD-2 is a rapid
      diagnosis method when clinical data are sugestive with active tuberculosis.
      However, due to the low positive predictive value, it would be convenient to
      obtain successive samples to confirm the result in patients without clinical
      evidence of tuberculosis.

PMID- 11333569
TI  - [Outbreak of Q fever and seroprevalence in a rural population from Soria
      Province].
AB  - BACKGROUND: The aim of this study was to describe an outbreak of acute fever in a
      rural town from Soria (Spain) in the spring of 1998 and to know the prevalence of
      IgG antibodies to Coxiella burnetii in this population. METHODS: 1. Outbreak of Q
      fever: epidemiological, clinical and analytical data were obtained by
      standardised questionnaire and the clinical records from all clinical cases.
      These cases were confirmed by complement fixation test.2. Seroprevalence: 253
      sera were chosen by not probabilistic sampling of convenience of sera samples
      collected between 1 September 1996 and 28 February 1999. Were regarded as
      positive anti-phase II C. burnetii IgG titles by indirect inmunoflourescence
      assay equal or higher to 1/80. RESULTS: 1. A total of 14 cases of Q fever with a
      mean age of 21.5 +/-3.1 years were confirmed. 64% presented pneumonia and in 36%
      the symptoms were nonspecific. No patient had direct contact with animals but
      near to the town there were 4 flocks with 2,614 sheeps overall. 2. The
      seroprevalence was 60% (95% confidence interval: 54-66). The seroprevalence was
      not increased with the outbreak (p > 0.05). CONCLUSION: The high prevalence of
      antibodies to C. burnetii in this population shows that this area is hyperendemic
      for such infection, but generally is asymptomatic or clinical signs are extremely
      mild because no cases of Q fever had been reported in the years before. Probably
      indirect exposure to flocks of sheep was the source of infection and transmission
      mechanism airborne.

PMID- 11333571
TI  - [Virology information in the Internet].

PMID- 11333570
TI  - [C reactive protein as marker of infection among patients with severe closed
      trauma].
AB  - BACKGROUND: Injury and infection are characterized by the activation of the acute
      phase proteins response. C-reactive protein (CRP), an acute phase protein, has
      been mentioned as an useful indicator of infection and sepsis in critically ill
      patients. OBJECTIVE: To study the evolution of serum CRP in patients with severe
      blunt trauma and to ascertain its ability as a biological marker of infection
      during the first seven days after injury. METHODS: We prospectively studied 54
      patients with blunt trauma (injury severity score>=16) age>14 years and length of
      the Intensive Care Unit (ICU) estay>= 7 days, over a 4-month period. Culture
      proven infections were collected and serum CRP was determinated every day, during
      the first week after ICU admission. RESULTS: Twenty-eight patients (51.8%)
      developed an infection during the first week, and the median day of diagnosis of
      infection was day 6. Pneumonia was the most common infection (50%) and Gram
      negative bacilli (63.3%) were the most common microorganisms recovered. Serum CRP
      levels were significantly higher in the infected patients group after day 4,
      showing a median value higher than 170 mg/l. Based on the receiver operating
      characteristic (ROC) curve analysis, a cutoff value of 109.5 mg/l for CRP gives a
      sensitivity of 78.6% and a specifity of 73.1% in predicting the presence of
      infection. CONCLUSIONS: The course of serum CRP levels is different in the group
      of patients with severe blunt trauma and infection, compared with the non
      infected group during the first week after injury and it could be an useful
      supplementary marker for infection after postinjury day 4. A value of 110 mg/l or
      higher for CRP should suggest an underlying infectious complication.

PMID- 11333572
TI  - [Recurrent abscesses in a renal transplant recipient].

PMID- 11333573
TI  - [Syncope and acute anemia in a young woman with fever and lymph node
      enlargement].

PMID- 11333575
TI  - [Risk factors for fecal colonization with glycopeptide-resistant Enterococcus
      spp. in an adult hospital].

PMID- 11333574
TI  - [Fever and pain in the inguinal-pubic area of five month's duration].

PMID- 11333576
TI  - [Encephalitis caused by primary infection with human immunodeficiency virus as a
      cause of acute confusional syndrome in an emergency department].

PMID- 11333577
TI  - [Disseminated disease by Mycobacterium kansasii resistant to isoniazid and
      rifampin in patients] with AIDS].

PMID- 11333578
TI  - [Rhabdomyolysis during a case of streptococcal toxic shock syndrome].

PMID- 11333579
TI  - [Exudative scalp lesion produced by Staphylococcus schleiferi].

PMID- 11333580
TI  - [Neisseria meningitidis meningitis after head trauma].

PMID- 11333581
TI  - [Causes of mortality among patients infected with the human immunodeficiency
      virus in the era of highly active antiretroviral therapy].

PMID- 11333582
TI  - [Nasopharyngeal myasis by third stage larvae of Oestrus ovis].

PMID- 11333583
TI  - [Paradoxical response to antitubercular treatment in patients with human
      immunodeficiency virus infection].

PMID- 11333584
TI  - [Antibiotic resistance for the year 2000].

PMID- 11333585
TI  - [Plasmatic concentrations of fibronectin as marker of clinical course among
      septic patients].
AB  - INTRODUCTION: It is difficult to follow up the patients with sepsis because of
      the underlying pathology or the presence of complications. The attending
      physician needs to know as soon as possible the response to the antibiotic
      therapy. Is therefore necessary to find real time biological markers that will
      help to understand the clinical situation of the infected patient. It has been
      demonstrated that fibronectin (Fn) is an early marker of sepsis, so it seemed
      plausible its use in the clinical monitoring of the septic patient. MATERIAL: We
      have used plasmatic concentrations of Fn in the follow up of sepic patients
      admitted to the Hospital de Segovia from February to August, 1995. There were two
      control groups: one of healthy volunteers and another of varied pathology.
      RESULTS: We have applied the multiple comparison rule of Bonferroni to
      demonstrate that plasma Fn is a negative acute phase reactant, with almost
      undetectable levels while the patient is in critical condition. An effective
      treatment prompts plasma Fn to rise significantly within two days. DISCUSSION:
      Plasma Fn concentration by itself or in an score system could help in the follow
      up of the septic patients.

PMID- 11333586
TI  - [Microbiologic profile in symptomatic pregnant women's genital secretions in Gran
      Buenos Aires, Argentina].
AB  - BACKGROUND: Establish the prevalence of microorganisms associated with genital
      colonization in symptomatic pregnant women. In order to review the evolution of
      frequent pathogens ecology and adjust the laboratory design, in a population
      attended at the public health Hospital, in the Great Buenos Aires. METHODS:
      Vaginal and endocervical samples, were explored for specific detection of
      Chlamydia trachomatis, Neisseria gonorrhoeae, Streptococcus agalactie,
      Trichomonas vaginalis, Candida spp., Mycoplasma hominis, Ureaplasma urealyticum
      and bacterial vaginosis (VB).Direct methods, culture, inmunodetection and PCR,
      were employed. In 1999; 198 women, with genital discharge, were studied. Age in
      the group range from 16 to 42 years old (Median 27 years old). RESULTS: In 51
      cases (25.7%) none of the above microorganisms or bacterial vaginosis were
      detected. In 30 cases (15.1%) bacterial vaginosis was diagnosed. Frequency of
      detection was: Ureaplasma urealyticum, 49,5%; Candida spp., 34,3%; Mycoplasma
      hominis, 14.1%; Streptococcus agalactie, 4.5%; Trichomonas vaginalis, 3.5%;
      Chlamydia trachomatis, 2.5%. No detection of Neisseria gonorrhoeae was
      demonstrated. CONCLUSIONS: There is a relevant frequency of bacterial vaginosis.
      On the other hand, lower prevalence of the Trichomonas vaginalis and Chlamydia
      trachomatis and also the absence of Neisseria gonorrhoeae was demonstrated.
      Culture for Streptococcus agalactie (at birth) and detection of Chlamydia
      trachomatis. must be extended to all pregnant women. Study of species and drug
      sensitivity of Candida spp., and detection of Ureaplasma urealyticum, Mycoplasma
      hominis and Neisseria gonorrhoeae, have to be explored under specific clinical
      requirement.

PMID- 11333587
TI  - [Significant bacteremias by Corynebacterium amycolatum: an emergent pathogen].
AB  - BACKGROUND: Corynebacterium sp. is an extremely varied genus which includes
      little known species and of which only Corynebacterium diphteriae,
      Corynebacterium urealyticum and Corynebacterium jeikeium are considered
      indisputable pathogens. Other species, such as C. amycolatum are at present being
      reconsidered as causative agents in infectious pathologies, partly on account of
      our greater aquaintance and improved identification techniques for these
      microorganisms and partly on account of the growing number of immunocompromised
      patients in whom all their pathogenic capacity is usually able to develope. We
      present 3 cases of significant bacteremia by C. amycolatum. METHODS: Bacterial
      isoliations from blood culture were obtained using the Vital Systems.
      Identification was performed by means of Gran stain, colony morphology, the
      results of numerous biochemical tests (including the Api Coryne systems), the
      behaviour of the strains against the vibriostatic agent O/129 and the antibiotic
      susceptibility pattern obtained with the E-test. RESULTS: The three isolates of
      C. amycolatum were obtained from patients after a lenghtly hospitalization, multi
      instrumentation and who had severe underlying disease. All three presented with
      concomitant isolates of C. amycolatum from other sites: sputum, wound and
      catheter respectively, which could explain the origin of the bacteremia. Colony
      morphology, antibiotic susceptibility patterns, resistance to the vibriostatic
      agent O/129 and the results of the biochemical test carried out were similar to
      those previously describe in the literature. CONCLUSIONS: C. amycolatum should be
      born in mind as a agent responsable for significant and severe pathology in this
      type of patient. In addition, it as certain specific characteristics which assits
      in its identification in the normal micr

PMID- 11333588
TI  - [Antibiotic prophylaxis and hernia repair. Systematic quantitative review
      results].
AB  - BACKGROUND: The usefulness of the antibiotic prophylaxis in hernia repair is
      currently a controversial subject. Comparative studies have shown disparate
      results, and that is why it is difficult to have a clear idea of its utility. The
      purpose of the present study is to make a systematic quantitative review or meta
      analysis of the published controlled studies on antibiotic prophylaxis in hernia
      repair, to give the best possible evidence as to the effectiveness of this
      prophylaxis. METHODS: The described steps for the realization of a systematic
      quantitative review, based on the practice of evidence based medicine, have been
      followed. The steps are these: formulation of a relevant question (is antibiotic
      prophylaxis useful in open inguinal hernia repair in the prevention of post
      operative infection of surgical wound?), search of the best available evidence,
      selection criteria of those trials found, analysis of each one of them,
      combination of the results (Yusuf and Peto method) and conclusions.Results.
      Twelve studies were found, of which eight fulfilled the inclusion criteria for
      the meta-analysis. Our results show that antibiotic prophylaxis in hernia repair,
      whether prosthetic material is used or not, diminishes the rate of infection by
      42%, 61% and 48% in herniorraphies, hernioplasties and the two combined,
      respectively. The number of patients to whom prophylaxis was administered in
      order to avoid a post-operative infection was 42 for herniorraphies, 37 for
      hernioplasties and 40 for general hernia repair.Conclusions. Antibiotic
      prophylaxis in hernia repair is useful in preventing wound infection.
      Nevertheless, this does not imply its indiscriminate administration, rather it is
      necessary to base it on the local rate of wound infection and on the analysis of
      the patients' risk factors in order to avoid its administration when the possible
      benefit is considered to be limited.

PMID- 11333589
TI  - [Trichomonas vaginalis: treatment and resistance to nitroimidazoles].

PMID- 11333590
TI  - [Infection of the surgical wound in a transplanted patient].

PMID- 11333591
TI  - [Torpid infection on a polycystic lung].

PMID- 11333592
TI  - [Acanthamoeba sp. keratitis in a patient not wearing contact lenses].

PMID- 11333593
TI  - [CDC EF-4 bacteremia].

PMID- 11333594
TI  - [Acute symptomatic lymphocytic meningitis due to varicella-zoster virus].

PMID- 11333595
TI  - [Pulmonary embolism in a patient with Q fever. Are the anticardiolipin antibodies
      the origin?].

PMID- 11333596
TI  - [Predominance of Campylobacter jejuni in cases of bacterial gastroenteritis in
      the adult].

PMID- 11333597
TI  - [Response of multiorganic hydatdosis to combined therapy with albendazoleand
      praziquantel].

PMID- 11333598
TI  - [Suppurative Haemophilus influenzae thyroiditis].

PMID- 11333599
TI  - [What should we know about Aspergillus?].

PMID- 11333600
TI  - [Telemedicine, e-Salud and infectious diseases].

PMID- 11333601
TI  - [Contribution to the early diagnosis of bacteremia: microbial growth detection in
      liquid culture media by ultrasound].
AB  - Nosocomial infection is an important problem because the number of patients daily
      affected in big hospitals. A big effort exists to develop techniques able to
      early detect the micro-organisms which cause the infection. The ultrasound is a
      mechanical radiology technique widely used in Medicine for diagnosis and therapy.
      It is also well known that this radiation can be used to control relative changes
      of several physico-chemical parameters in liquids. As an example, the velocity an
      attenuation of acoustic waves coming through a liquid can be accurately measured.
      The developed technique consists of an ultrasonic chamber immersed into a
      thermostatized water bath with two transducers operating in through-transmission.
      Different culture bottles were placed in between the transducers to live the
      ultrasound to come across the sample. Several micro-organisms with controlled
      concentrations, chosen between the most common in sepsis clinical, were used to
      inoculate each bottle. In the case of aerobic metabolism, the carbon dioxide gas
      produced by bacteria introduce elastic changes into the liquid which modify both
      the propagation velocity and the attenuation of the ultrasound. The continuous
      monitoring of the time-of-flight and the amplitude of an ultrasonic pulse coming
      through the sample give us a clear indication of the metabolism process. The
      signatures observed permits the identification of algorithms to early define the
      positive cases. The developed technique is faster than other commercial systems.
      The intrinsically non-invasive characteristic of the ultrasound and the relative
      cheapness of the technique open new attractive possibilities in microbiological
      diagnosis.

PMID- 11333602
TI  - [Aeromonas spp bacteremia: study of 12 cases and review of the literature].
AB  - Twelve cases of Aeromonas spp. bacteremia are here reviewed in adult patients
      occurred at our institution during a 6-year period. Three cases corresponded to
      patients with hematological disease and four had a solid neoplasm. The source of
      infection in seven patients was extra-nosocomial; infections in the five
      remaining patients were considered to be acquired in the hospital. In seven
      patients, potential portals of entry were found. The usual clinical presentation
      was febrile syndrome in all cases and only in two patients did the clinical
      picture evolve to fulminant septic shock. Speciation of microorganisms was
      determined in only four cases: 2 A. hydrophilia, 1 A. caviae, and 1 A. veronii.
      Most isolates were susceptible to aminoglycosides, cotrimozazol, phosphomycin,
      and quinolonos, and resistant to ampicillin. Three patients (25%) died as a
      result of the infection. Aeromonas spp. bacteremia represented 0.12% of blood
      cultures in our hospital and occurs in immunosuppressed patients although it may
      be reported in previously healthy individuals.

PMID- 11333604
TI  - [The elimination of leprosy in the year 2000: what will be the fate of Antonio
      and Bajamut].

PMID- 11333605
TI  - [Hyperhidrosis and multiple nodules in the hairs of the axilla].

PMID- 11333603
TI  - [Importance of the bacterium-host interaction in coagulase-negative staphylococci
      isolated from neonates].
AB  - OBJECTIVE: Neonates represent a high risk population for infections by coagulase
      negative staphylococci (CNS). To have a better understanding of these process our
      purpose was to compare the expected result of the bacterium-host interaction
      given by the neonates' risks factors and the micro-organisms' virulence factors
      with the condition of infecting or colonising strain that emerge from the
      diagnosis on the basis of the clinical symptoms. METHODS: We studied 24 neonates
      who were submitted to an epidemiological control establishing as risk factors:
      catheters, vesicle sounds, previous surgery and immunodepressed conditions. In
      the CNS recovered from clinical samples we determined the following virulence
      factors: synergistic hemolysis, slime production, adherence to Teflon catheters
      and hydrophobicity. RESULTS: We found correlation between the clinical diagnosis
      and the expected result of the bacterium-host interaction in 21 patients (87.5%).
      Among them, in 8 patients infection didn't occurred in spite of having the micro
      organisms 3 from 4 virulence factors since the patients didn't have risk factors.
      CONCLUSIONS: A microbiological study based entirely on identification and
      treatment can alter the biological context. It is necessary to understand the
      bacterium-host interaction for an appropriate comprehension of the bacterial
      diseases.

PMID- 11333606
TI  - [Fever of unknown origin and retroperitoneal adenopathies in an immunocompetent
      woman].

PMID- 11333607
TI  - [Fever and skin lesion in 70 year old men with Hodgkin's lymphoma].

PMID- 11333608
TI  - [Training of non-medical professionals to practice clinical microbiology].

PMID- 11333609
TI  - [Paraneoplastic Clostridium septicum bacteremia].

PMID- 11333610
TI  - [On the pathogenicity of Enterococcus spp].

PMID- 11333611
TI  - [Evaluation of three methods of diagnosis of Clostridium difficile infection].

PMID- 11333612
TI  - [Streptococcus suis meningitis. Report of two cases and literature review].

PMID- 11333613
TI  - [Neisseria meningitidis pneumoniae in a 47 year old woman with systemic lupus].

PMID- 11333614
TI  - [Bacteremia due to Campylobacter jejuni: report of two cases].

PMID- 11333615
TI  - [Pleural empyema due to Gemella morbillorum].

PMID- 11333616
TI  - [Resistance and therapy of Streptococcus pneumoniae].

PMID- 11333617
TI  - [The new European health strategy: an opportunity for Spanish public health].

PMID- 11333619
TI  - [Socio-economic factors associated with preterm delivery. Results of the European
      project in Spain].
AB  - OBJECTIVES: The objectives of this paper were to analyse the effect of social,
      personal and medical risk factors on preterm birth (moderate versus very preterm)
      or on two preterm birth groups (spontaneous versus indicated). METHODS: Results
      from the Spanish collaborating centre of the European multicentre case-control
      study EUROPOP (European Program of Occupational Risks and Pregnancy Outcome) are
      presented. All preterm births (529) between 22 and 36 completed weeks of
      amenorrhea and 788 births of 37 or more completed weeks of amenorrhea (control
      group) are included. Explicative variables are divided in social, personal and
      medical factors. A univariate and multivariate analysis by means of a logistic
      regression were carried out. RESULTS: Very preterm birth risk was higher for
      women over 34 years, adjusted OR: 2.53 (1.42-4.52), with lower educational level,
      adjusted OR: 1.79 (1.07-2.98), for primigravid women or multigravid women with
      only first trimestre abortion, adjusted OR: 1.86 (1.13-3.04), and for multigravid
      women with previous preterm birth or second trimestre abortion, adjusted OR: 5.53
      (2.97-10.35). A similar trend was observed for moderate preterm birth.
      Probability of spontaneous preterm birth was higher for mother over 34 years,
      adjusted OR: 1.51 (1.01-2.26), with lower income, adjusted OR: 1.75 (1.07-2.88)
      and for multigravid women with previous preterm birth or second trimestre
      abortion, adjusted OR: 2.96 (1.86-4.71). Results were similar for indicated
      preterm birth. CONCLUSION: Social differences were found to be related to
      moderate and very preterm birth. No differences were observed between risk
      factors and kind of preterm birth: spontaneous or indicated.

PMID- 11333620
TI  - [Evolution of childhood hospitalization in Spain. Variation among autonomous
      communities].
AB  - BACKGROUND: To describe trends in children hospitalization in Spain during 1985
      1994 and its variability among regions. METHODS: Description between 1985 and
      1994, by autonomous regions, of the evolution in the rates of available beds,
      discharges, stays and visits and average length of stay, from data provided by
      the health care centres with inpatient statistics. RESULTS: The average length of
      stay decreased 23.9%, but there was a 4.5% increase in bed availability, a 39.5%
      increase in the discharges rate and 36.8% in the visits rate. Regions showed
      large differences in all indicators, that trends to converge in beds availability
      and discharges, but not in length of stay and visits rate. CONCLUSIONS: There has
      been an increase in hospital performance with strong variation among regions.
      Differences tends to reduce in some indicators but not in others.

PMID- 11333621
TI  - [Quality of life in patients with eating disorders].
AB  - OBJECTIVE: To evaluate the quality of life of ambulatory patients with eating
      disorders in relation to the severity of their symptomatology and in comparison
      with other psychiatric disorders and general population values. METHODS: Cross
      sectional descriptive study of the quality of life of 180 patients recruited at
      an eating disorders unit. In order to study different aspects of their Health
      Related Quality of Life, the SF-36, the EAT and the HAD questionnaires were used.
      The results of the SF-36 were compared to population values of the same gender
      and age, and to other studies of psychiatric disorders where the SF-36
      questionnaire was used. RESULTS: Patients with eating disorders presented worse
      quality of life than the general population of the same gender and age, and
      similar to patients with other psychiatric diagnoses, as schizophrenia,
      depression or panic disorder. No significant differences were found between
      patients with diagnoses of restrictive anorexia, purgative anorexia and bulimia.
      Mental health, rol emotional and vitality were the most affected areas of the SF
      36. CONCLUSIONS: This study shows the severity of these disorders, which have a
      special incidence in young active women. This fact is becoming an important
      public health problem and raises the need of specialised assistance.

PMID- 11333622
TI  - [Assessment of quality of life in lung cancer patients].
AB  - OBJETIVES: The aim of this study was to describe lung cancer patients' quality of
      life, measuring physical, psychological and social parameters, and general and
      specific symptoms of the disease using different questionnaires. METHODS: 103
      primary lung cancer patients who were between 20 and 80 years old and recruited
      during one year were included. All patients fulfilled the generic health related
      quality of life (HRQoL) questionnaire SF-36 and the specific EORTC-C30. Also
      sociodemographic and clinical important data were collected. Differences in
      aspects of perceived quality of life by diagnostic group and stage were analysed.
      RESULTS: The results indicate that the patients with a higher disease stage had
      worse perception of their quality of life in comparison with patients in a lower
      stage of the disease. Likewise, small cell lung cancer patients, overall, showed
      a worse perception of their quality of life than non-small cell lung cancer
      patients. These differences were shown either by generic and the specific
      questionnaire scores. CONCLUSIONS: The results obtained in the study show that
      the SF-36 and EORTC capture the differences in the perceived quality of life in
      patients by diagnosis and evolution stage of the disease. All quality of life
      areas were already affected at the moment of the diagnosis of the disease. The
      scores of both questionnaires are coherent with clinical evaluation, based on the
      clinical stage, which support the discriminative validity of those instruments.

PMID- 11333623
TI  - [Drug expenditure in primary care: associated variables and allocation of drug
      budgets according to health district].
AB  - OBJECTIVES: Identify factors explaining variability in prescribing costs after
      reviewing ecological data related to costs and socio-demographic characteristics
      of the health care zones in the autonomous region of Valencia, and explore the
      usefulness of using the model to set prescribing budgets in basic healthcare
      zones. MATERIALS AND METHODS: An ecological analysis of the value socio
      demographic characteristics and use of healthcare services to explain prescribing
      costs in 1997. Development of a prediction model based on multiple linear
      regression in data for prescribing costs in 1997 and validation in data for 1998.
      RESULTS: Factors that correlated positively with prescribing costs were the
      percentage of inhabitants over the age of 80, the death rate, the percentage of
      inhabitants with only primary education or less, the percentage of inhabitants
      between the ages of 65 and 79 and the distance from the capital city. A
      multivariate model including the death rate, the percentage of inhabitants 80
      years of age and older, the number of cars per 100 inhabitants and number of
      visits per inhabitant accounted for 44.5% of the variations in prescribing costs
      in 1997 and 32% in 1998. CONCLUSIONS: Socio-demographic factors and certain
      variables associated with health care utilization can be applied, within certain
      limitations, to set prescribing budgets in basic healthcare zones.

PMID- 11333624
TI  - [HIV/AIDS prevention in prisons: experience of participatory planning].
AB  - OBJECTIVE: To describe the application of participatory methodology in the prison
      setting for the determination of the most appropiate contents and methods of a
      HIV/AIDS prevention program. METHODS: Community study in the Centro de
      Cumplimiento del Establecimiento Penitenciario in Valencia (1250 inmates) in
      Spain. The study was carried out in two phases: identification of key informants
      and collection of information. In the second phase, a community forum composed of
      the center's male and female inmates was created, personal interviews with
      convicted female prisoners were carried out and a self-administered questionnaire
      was distributed to the center's health professionals and management as well as to
      health promotion experts. RESULTS: Community forum. The following proposals for
      HIV/AIDS prevention were made by the male and female prisoners: a) those directed
      at the prisoners themselves: increasing preventive mesures in material used in
      injection and in sexual relationships; b) those directed at the prison
      management: increased distribution of condoms, safety razors and bleach and the
      introduction of sterile injection material. In the personal interviews, agreement
      on a future prevention program was high among the female inmates and the other
      key informants. Preferred measures were the acquisition of information on the
      mechanisms of HIV transmission and prevention and on the differences between HIV
      carriers and those suffering from AIDS and the acquisition of skills for
      disinfecting material used for drug injection and in negotiating the use of
      condoms with partners. The preferred methodology was based on groups that would
      allow for an interchange of experience and would deal with the difficulties of
      putting preventive measures into practice. CONCLUSIONS: The participation of the
      prison's inmates and staff supplied information that facilitated the design
      (choice of aims, measures, methods and resources) of an HIV prevention program
      adapted to the needs and preferences of all the interested parties.

PMID- 11333625
TI  - [Chlorination of drinking water in Spain and bladder cancer].
AB  - OBJECTIVES: Drinking water chlorination generates trihalomethanes and other by
      products with mutagenic and carcinogenic properties in animal experiments.
      Epidemiological studies have associated trihalomethanes to an increased risk of
      bladder cancer. We evaluate trihalomethane levels in four Spanish areas and
      calculate the bladder cancer risk attributable to this exposure. METHODS:
      Trihalomethanes have been analysed in 111 drinking water samples from four
      Spanish areas using gas chromatography. Water utilities were contacted and
      information on drinking water consumption in Spain has been collected. We
      reviewed the epidemiological studies that assess the association between bladder
      cancer risk and exposure to chlorination by-products. Attributable risk was
      calculated on the basis of these levels, mortality data per area and risk
      estimates obtained from the literature. RESULTS: Mediterranean areas present the
      highest levels of trihalomethanes with 81, 80, 61 and 52 ug/l in Sabadell,
      Alicante, Barcelona and Manresa respectively. Lower levels are found in Tenerife
      and Asturias with 7 and 20 ug/l respectively. The bladder cancer attributable
      risk in high trihalomethane exposure areas may be, on average, around 20%.
      CONCLUSIONS: The trihalomethane levels found are high compared to those of other
      European Union countries. In the high exposure areas, drinking water chlorination
      may generate a considerable number of bladder cancer cases. These estimations
      have to be carefully interpreted and verified with more extensive studies.

PMID- 11333626
TI  - [Health status and gender in Catalonia. An approach using the information sources
      available].
AB  - OBJECTIVE: To present health status differences between men and women in
      Catalonia across the main available data sources. METHODS: The main institutional
      health data sources of the Catalan population are presented. Mortality and
      morbidity differences by gender are studied. RESULTS: Men die before than women
      and present more frequently pathologies that require hospitalary care. Unhealthy
      behaviours are more frequent in men than in women. Women in general, in all
      social classes, present more frequently chronic disorders and disabilities and
      declare worse perception of health status than men of the same social class.
      CONCLUSIONS: Institutional sources of data available in Catalonia allow the
      description of gender differences in health, nevertheless new variables should be
      included to improve gender perspective analyse.

PMID- 11333627
TI  - [Population attributable fraction: estimation and interpretation].
AB  - The goal of this paper is to revise the concept, estimation methods, and
      interpretations of the population attributable fraction. From the usual formula
      of the population attributable fraction: (Ip - I0) / Ip, where Ip is the
      cumulative incidence in the overall population, and I0 is the cumulative
      incidence in the non-exposed group, other formulae are presented for use in
      exposures with more than two levels, and in the presence of confounding factors.
      Differences in estimation methods between cohort and case-control studies are
      discussed, and equations to estimate confidence intervals are displayed. Finally,
      some interpretations --including the concepts of "etiologic case" and "case in
      excess", suggested by Greenland and Robbins--, and some habitual errors are
      discussed.

PMID- 11333628
TI  - Applying economics in a hostile environment: the health sector.
AB  - In this paper we state that health economics is now amongst the leaders in a
      "paradigm shift" in economics that needs to spread as quickly as possible into
      the rest of the subject. This conclusion is obtained from considering that
      economics can be applied to topics that do not appear superficially to be
      economic topics such as what is the best treatment for a national health service
      to offer to a patient with a particular disease.

PMID- 11333629
TI  - [GLOBAlink: an international network for the prevention and control of smoking].

PMID- 11333632
TI  - [Complex sampling designs].

PMID- 11333634
TI  - [Legionella: a problem of public health and a problem for public health].

PMID- 11333635
TI  - [Prevalence of obesity in the population assisted at primary health care services
      in Girona, 1995-1999].
AB  - OBJECTIVES: To estimate the prevalence of obesity and overweight in the
      population of Girona (Spain) between 1995 and 1999 and to divide the prevalences
      in geographical areas according to age and sex. METHODS: Height and weight were
      directly measures in 24,554 health care consumers older than 14 years (10,595 men
      and 13,959 women) treated in four primary health care areas: Girona 1, Girona 4,
      Salt and Camprodon and in one primary health care center in the province of
      Girona. Body mas index (BMI) was calcuted by dividing weight in kilograms bye
      height in meters squared. Obesity was defined as grades II and III of Garrow's
      index (BMI >= 30 kg/m2) and overweight as degree I (25 kg/m2 >= BMI < 30 kg/m2).
      Because the sample was not randomized, the prevalences were adequately weighted.
      The comparison between prevalences in two different primary health care areas for
      each sex (in the same Garrow's index and age group) was carried out using a
      parametric test of differences in proportions (Student's t-test). A hierarchical
      logistic regression was used to compare prevalences in the same grade Garrow's
      index, controlling for age and sex. RESULTS: The prevalence of obesity was
      estimated as 15.6% in men aged from 20-74 years (from 14.0% in Girona 1 to 22.4%
      in Camprodon) and 17.5% for women (15.6% in Girona 1, 22.7% in Camprodon). The
      weighted mean was 16.7%. The prevalence of overweight was 44% in men and 33% in
      women and the weighted mean was 37.8%. The prevalence of obesity was graduated
      with statistically significant differences between Girona 1, Salt, Girona 4,
      Camprodon and Sils. CONCLUSIONS: The estimates of the prevalences of obesity and
      overweight obtained in this study were closer to those of other studies in
      similar populations than previously believed. Indeed, the prevalences may be
      similar to those of the European Union and, in some age groups, to those of the
      United States.

PMID- 11333636
TI  - [Prevalence and duration of breastfeeding in Asturias].
AB  - OBJECTIVE: To estimate the prevalence and duration of breastfeeding, and factors
      associated with them, in Asturias (Spain). METHODS: A cross-sectional study was
      carried out. A stratified random sample of 453 infants was drawn on a population
      of 4,326 infants aged 0-8 months at the time of the study. Sociodemographic data,
      and information on pre- and perinatal care were obtained through a telephone
      survey in which mothers were also asked whether they were breastfeeding on the
      day of the telephone call. A univariate logistic regression model was used to
      estimate the prevalence curve of breastfeeding according to infant age, and
      multiple logistic regression was used to determine the associations between the
      prevalence and covariates. The discontinuity index (DI) and the cumulative
      breastfeeding index (CBI) were also estimated as indicators of duration. RESULTS:
      A total of 418 telephone calls were made. The prevalence of initial exclusive
      breastfeeding was 51.4% (95% CI: 46.6-56.2%) which decreased to 14.9% at day 90
      and to 8.7% at day 120. The DIs were 28.6% at day 30 and 71% at day 90. In the
      multivariate analysis the prevalence of exclusive breastfeeding was higher among
      mothers living in a rural or suburban area (OR = 5.69 and OR = 3.55,
      respectively), than among those living in urban areas. The prevalence was also
      higher among mothers with a university degree (OR = 3.90; 95% CI: 1.77-8.58), and
      among those who had been seen by a midwife during pregnancy (OR = 2.13; 95% CI:
      1.04-4.38). A negative correlation was found between exclusive breastfeeding and
      the newborn having received food supplements during the first hours after birth
      (OR = 0.43; 95% CI: 0.20-0.95). CONCLUSIONS: The prevalence of breastfeeding in
      Asturias, and especially its duration, is much lower than that recommended by the
      World Health Organization. Mothers living in urban areas do not follow the most
      appropriate patterns of breastfeeding.

PMID- 11333637
TI  - [Risk factors associated with nosocomial bacteremia in low birth weight neonates.
      Grady Memorial Hospital, Atlanta].
AB  - BACKGROUND: Nosocomial bloodstream infections occur frequently in Neonatal
      Intensive Care Units and are associated with recognized and unrecognized risk
      factors. Little has been published regarding risk factors for bloodstream
      infections in low birth weight neonates. OBJECTIVE: To investigate risk factors
      for bloodstream infection in neonates < 1,500 g admitted at a Neonatal Intensive
      Care Unit. METHODS: A prospective study was undertaken in low birth weight
      neonates (< 1,500g) during a 22 months period. Bivariant, and logistic regresion
      (stepwise procedure) analysis was used to determine the significance association
      of bloodstream infection and perinatal and nosocomial risk factors. RESULTS: A
      total of 72 patiens with nosocomial bacteriemia and 147 non bacteriemic patients
      were studied. Independent risk factors associated with bloodstream infection were
      birth weight, persistence of umbilical catheter > 7 days and persistence of
      peripheral arterial catheter > 1 day. CONCLUSIONS: The uses of umbilical catheter
      > 7 days, peripheral arterial catheter > 1 day and birth weight < 1,500 g were
      significant determinants of nosocomial bloodstream infection risk. Because of the
      importance of invasive procedures as a source of nosocomial bloodstream
      infections, the lines duration needs to be reviewed with the aim of reducing the
      incidence of blood stream infection.

PMID- 11333638
TI  - [Variability in preventive activities among primary care teams in Catalonia.
      Application of a multilevel analysis].
AB  - OBJECTIVES: To determine whether variability exists among primary care teams
      (PCTs) in Catalonia in opportunistic screening activities (screening for smoking,
      drinking, hypertension and tetanus vaccination) and to analyze the explanatory
      factors in the individual characteristics of the population treated and the
      characteristics of the PCT. METHODS: A multilevel analysis with individual and
      PCT explanatory variables was performed. The data were draw from a sample of
      3,000 clinical histories from the adult population treated in 1995 in 30 PCTs
      from the restructured primary care network in Catalonia and from PCT
      characteristics. RESULTS: The recording of preventive activities in the clinical
      histories increased with the number of risk factors and/or diseases diagnosed,
      the number of other preventive activities recorded, and age. Recording of
      arterial pressure was more frequent in women while the remaining preventive
      activities were more frequent in men. Workload impeded opportunistic detection.
      Greater recording of antitetanus vaccination was associated with the number of
      years that the PCT had been functioning and with wider geographical area.
      Recording of smoking was higher in urban areas. CONCLUSIONS: Variability in
      opportunistic detection exists among PCTs in Catalonia. The characteristics of
      the PCT and the population treated that explain part of this variability are
      identified. Lower workload favors preventive activities in primary care.

PMID- 11333639
TI  - [Hospitalizations due to ambulatory care sensitive conditions: selection of
      diagnostic codes for Spain].
AB  - BACKGROUND: Hospitalisations due to Ambulatory Care Sensitive Conditions (ACSC)
      are considered an indicator to measure the use of hospital services because of
      health conditions that could have been prevented and controlled by primary health
      care. The objective of this study is to select the list of diagnostic codes to
      assess the performance of primary health care in Spain. METHODS: The five
      criteria proposed by Weissman and Solberg, to select an appropriate indicator,
      were applied to a first list of 87 ACSC diagnostic codes identified through
      bibliographic search. Information on two main criteria-whether care for a health
      condition was a primary health care role and whether hospitalisation was needed
      once the health problem occurred was obtained by means of the Delphi technique. A
      group of 44 experts gathered together for the study. For the remaining criteria,
      information came from the results of the Pilot study on hospitalisations due to
      ACSC in Catalonia, Spain. Meeting the five criteria was the criterion selected to
      evaluate the solving ability of primary health care. RESULTS: a) from the Delphi
      group: 42 (95.4%) participants completed the three rounds. The question on
      whether the care of the selected health conditions was responsibility of primary
      health care reached a high level of consensus (between 86.1 and 100%). The
      consensus on the need for hospitalisation was lower, from 75.7 to 88.6%,
      moreover, 5 diagnostic codes did not reach the established consensus, and b) from
      the ACSC selection process: five diagnostic codes did not meet the criteria and
      were excluded. Out of the remaining 82, all them were considered as health
      problems to be cared for at primary level and in 37 cases hospitalisation was
      considered always as necessary. Thirty-five diagnostic codes, that met the five
      criteria, represented the set of ACSC diagnostic codes in our setting.
      CONCLUSIONS: A set of 35 diagnostic codes of ACSC, adapted to our setting, is
      proposed to evaluate primary health care performance. The selected codes reduce
      significantly the limitations that stem from hospital admission criteria due to
      patient clinical characteristics, variations in hospital medical practice, and
      hospital admission policies.

PMID- 11333640
TI  - [Validation of the Job Content Questionnaire in hospital nursing staff].
AB  - OBJECTIVE: The aim of this study was to determine the reliability and construct
      validity of the three dimensions of the Job Content Questionnaire (JCQ): demand,
      control and job support among hospital nursing staff. METHODS: The minimun
      reduced version of the JCQ was used, which include three dimensions:
      psychological demands (9 items), job control (9 items) and job support (11
      items). Validity was assessed in a random sample of 330 nursing staff from two
      general hospitals in the province of Alicante (Spain). The reliability of the
      questionnaire was evaluated after re-interviewing a subsample of 50 nurses 15
      days after the first interview. Construct validity was evaluated by calculating
      correlations between the three dimensions of the JCQ obtained after factorial
      analysis with the burnout scale and six dimensions of the 36-item short-form
      health survey (SF-36) questionnaire. RESULTS: Factorial analysis revealed that
      the version of the JCQ validated in this study had the same factorial structure
      as the original questionnaire. The intraclass correlation between the first and
      second interview was high for each of the three dimensions (between 0.83 and
      0.87). Cronbach's alpha was also high (between 0.74 and 0.88). A moderate but
      significant correlation was found between the three JCQ dimensions and the
      burnout scale: (-0,27 for job support, 0.31 for psychological demands and -0.12
      for job control). A moderate correlation was also found for some SF-36
      dimensions. CONCLUSION: The factorial structure of the JCQ was similar to that
      proposed by the author in the context of Spanish culture. The reliability and
      internal consistency of each of the three dimensions was high while construct
      validity was moderate.

PMID- 11333641
TI  - [Housework, gender and health in the working population].
AB  - OBJECTIVE: To analyse the relation between domestic workload and self-perceived
      health status among workers and to examine whether there are gender inequalities.
      METHODS: The selected population were the 215 men and 106 women younger than 65
      years interviewed in the Terrassa Health Survey, 1998 who had a paid work and
      were married or cohabiting. Adjusted odds ratios (aOR) by domestic workload, age
      and occupational social class with their 95% confidence intervals (CI) were
      calculated. RESULTS: Whereas among men domestic workload was not associated with
      health status, among women poor self-perceived health status was positively
      related to household size (aOR = 3.65; 95% IC = 1.06-12.54) and to lack of a
      person for doing domestic tasks (aOR = 4.43; 95% CI = 1.05-18.62). CONCLUSION:
      Both household characteristics and having a support for facing domestic tasks
      play an important role in gender health inequalities.

PMID- 11333642
TI  - [Effects of population aging on health care expenditure: myths and facts].
AB  - Over the last 30 years, the elderly population of developed countries has shown
      an unprecedented increase. This process has raised alarm about the future
      affordability of health care systems. In this context, we consider the effects of
      population aging on health care expenditure within a process involving several
      elements: the increasing number of elderly persons, variations in the health
      status of the elderly and the evolution of the cost of medical treatment. The
      main conclusion is that only a small part of the increase in expenditure is due
      to population aging. Furthermore, because the average health status of the
      elderly has improved with greater longevity, we suggest that most of the increase
      in health care expenditure can be attributed to the evolution of non-demographic
      factors. Such as health services utilization, treatment cost and the development
      of new medical technology. Unlike populations aging, these factors can be
      subjected to future regulation and consequently, can to a large extent be
      controlled.

PMID- 11333643
TI  - [Public health functions, activities and structures: the role of large and middle
      sized municipalities].
AB  - OBJECTIVE: The aim of this paper was to analyze how public health functions are
      covered in large or medium-sized cities in Catalonia (Spain) by assessing the
      role, activities and structure of local services. METHODS: Data were collected
      through a questionnaire with items on public health functions and activities and
      on the structure of municipal services. The study population comprised the 43
      cities of Catalonia with a population above 25,000 (3% of towns and 70% of the
      population). Answers were obtained from 28 cities (65%), covering 60% of the
      population of Catalonia and all towns with a population above 50,000 inhabitants.
      RESULTS: The public health function in which local governments were least active
      was need assessment while they were more active in policy development and service
      delivery assurance. For public health activities, the role of local governments
      was relatively greater in health protection while few municipal services were
      active in epidemiological surveillance and substance abuse. Municipal public
      health expenditure per resident/year was estimated at 1,063 pesetas
      (approximately 6 Euros). Among the public health personnel, 72% worked full-time
      while the remaining (mainly members of the corps of health officers serving local
      administration) worked part-time. Local governments often mixed within the same
      structure public health services and services, mainly consumer affairs,
      environmental or social services. CONCLUSIONS: Local governments showed
      significant activity in public health. The volume of resources involved and
      management capacity were considerable. In some cities, some public health
      activities were perceived as not covered.

PMID- 11333644
TI  - [Public hospital payment system in Spain: the experience of Catalonia and
      Andalusia].
AB  - Since the mid-1990s, the introduction of new public hospital payment systems to
      improve the efficiency of Spanish hospitals within the context of managed
      competition has been debated. Blended systems, which recognize the importance of
      the activity performed, as well as the role of the hospital in the public health
      system, have emerged as the best-matched tools both in risk assignment and in
      efficiency-economic feasibility dialectic. In this article, the payment method
      used in Catalonia since 1997 is analyzed and contrasted with that introduced in
      Andalusia in 1998. The evaluation focuses on the instruments used to incorporate
      the mixed model in the two different settings. On the one hand, the capacity of
      diagnosis related groups (DRGs) to define hospital product cost is limited.
      Furthermore, DRGs require numerous adjustments before introduction into Spain. On
      the other hand, structural level can be defined through the Grade of Memberships
      in Catalonia and the Basic Centers in Andalusia. We also analyze the introduction
      of the different methods into Spain and their adaptation to the Catalan and
      Andalusian environments. The transition periods seem not to have led to a
      definitive solution and have served to highlight the fragility of the instruments
      used and of the use that has been made of them. We conclude that the introduction
      of new tools to improve hospital efficiency through payment systems was
      precipitate and, to a certain extent, naive. Public hospital payment systems can
      be considered to be effective when they manage to allocate resources over a
      period of time. Ensuring the efficiency of public hospitals implies daily work on
      the part of each hospital and the information systems generated by regional
      health systems and will not be achieved through external financial tools poorly
      adapted to the setting in which they are applied.

PMID- 11333650
TI  - ?

PMID- 11333645
TI  - [Poliomyelitis eradication in areas with armed conflict: the case of
      Afghanistan].
AB  - The aim of this study was to describe fieldwork to erradicate poliomyelitis from
      Afghanistan and particularly from the Mazar Region. From 1997-1999, 365 cases of
      acute flaccid paralysis were detected. Of these, 216 cases (59.2%) were
      classified as poliomyelitis. The rate of acute flaccid paralysis improved from
      0.1 in 1997 to 0.8 in 1999. Fieldwork in the Mazar region revealed under
      notification and the need to improve surveillance methods. However, massive use
      of the services of traditional healers and extreme transport difficulties reduced
      the efficacy of the interventions. The case of Afghanistan suggests that
      epidemiological surveillance systems are feasible in countries with armed
      conflict, although such systems require considerable resources.

PMID- 11333652
TI  - ?

PMID- 11333651
TI  - ?

PMID- 11333653
TI  - [Informed consent in gastrointestinal endoscopy. Who should inform?]

PMID- 11333654
TI  - [Why are not all patients with chronic liver disease associated with hepatitis C
      virus treated?].
AB  - AIMS: To analyze the prevalence of patients with chronic liver disease associated
      with hepatitis C virus (HCV) not undergoing antiviral treatment and the reasons
      for which this treatment was not indicated. PATIENTS AND METHODS: 718 patients
      with HCV infection referred for therapeutic evaluation between January 1990 and
      January 1998. Demographic, clinical, biological and histological variables were
      prospectively analyzed. The patients were divided into two groups: treated and
      untreated. RESULTS: 393 patients were treated and in 325 patients antiviral
      treatment was not considered to be indicated. The most frequent reasons for not
      starting therapy were advanced age, the presence of decompensated cirrhosis and
      the patients' refusal to undergo antiviral treatment. CONCLUSIONS: A broad
      subgroup of patients with chronic liver disease associated with HCV do not
      receive antiviral treatment. This is related with: a) patients' advanced age at
      diagnosis, b) diagnosis at the advanced stages of the disease, and c) patients'
      refusal to undergo such treatment after being informed of its potential risks and
      benefits.

PMID- 11333655
TI  - [Infectious complications associated with liver transplantation: analysis of 104
      patients].
AB  - OBJECTIVE: Infectious complications are the main cause of morbidity and mortality
      during the first year after liver transplantation. The aim of the present study
      was to determine the incidence, microorganisms and factors associated with the
      development of infectious complications. PATIENTS AND METHOD: Retrospective
      analysis of infectious episodes during the first year after transplantation in
      104 patients undergoing transplantation between April 1995 and December 1996. The
      various clinical variables related to the pre-transplant disease, the surgical
      intervention and post-transplant evolution were evaluated with the aim of
      identifying predictive factors for the development of bacterial infectious
      complications. RESULTS: During the first year, 51 patients (49%) presented 111
      infectious episodes. The most frequent infections were bacterial (66%); 21% were
      cytomegalovirus infections and 22% were fungal. The incidence of bacterial
      infections was highest during the first month (80% of all infectious episodes in
      this period). Two variables were independently associated with the development of
      bacterial infections in the first month following transplantation: prolonged
      ischemia of the graft (p = 0.002) and length of stay in the intensive care unit
      (p = 0.002). Infectious complications caused 8 of the 11 deaths that occurred
      during the 1-year follow-up. Mortality associated with invasive fungal infections
      was 100%. CONCLUSIONS: Although the overall incidence of infections and
      associated mortality has decreased, it remains the main cause of mortality and
      morbidity in the first year after transplantation.

PMID- 11333656
TI  - [Upper gastrointestinal tract injury caused by ingestion of caustic substances].
AB  - BACKGROUND: To determine the distribution, extension and severity of injuries
      produced by the ingestion of caustic substances in the upper gastrointestinal
      tract, and to assess the relationship of these factors with the type of caustic
      substance ingested, whether intake was accidental or deliberate and the
      appearance of strictures or death. PATIENTS AND METHOD: Between 1993 and 1999,
      138 patients (74 males and 84 females) who underwent upper gastrointestinal
      endoscopy in our unit within the first 24 hours after ingestion of caustic
      substances were included in the study. Mean age was 47 years (14-97 years). The
      severity of caustic injury was evaluated using the classification of Showkat et
      al. RESULTS: The type of caustic substance ingested was as follows: lye in 84
      patients (53%), nitric acid in 21 (13%), different caustic mixtures in 43 (27%)
      and unknown in 10 patients (6%). Lesions were grade I in 51 patients(32%), grade
      II in 33 (21%) and grade III in 20 (13%). No lesions were seen in 54 patients
      (34%). Of the 158 patients, gastric injury was found in 91 (57.5%), esophageal
      burn in 72 (45.5%) and duodenal injury in 28 (18%). Ingestion was accidental in
      80 patients (51%) and voluntary in 62 (39%); the reasons for ingestion were
      unclear in 16 patients (10%). Voluntary ingestion and acid use were associated
      with greater severity of lesions (p < 0.0005). Eight patients (5.0%) died, 10
      patients (6.3%) required emergency surgery, and 7 (4.4%) developed esophageal
      gastric strictures that required surgery or endoscopic treatment. CONCLUSIONS:
      The most common type of caustic substance ingested was lye. In 66% of the
      patients, lesions were absent or superficial. The more severe injuries, producing
      strictures and higher mortality, were related to voluntary and nitric acid
      ingestion. The part of the digestive tract most frequently affected after lye and
      acid ingestion was the stomach.

PMID- 11333657
TI  - [Good response to colchicine in amyloidosis secondary to inflammatory bowel
      disease].
AB  - Acquired systemic amyloidosis may develop during the course of a number of
      chronic inflammatory diseases, including inflammatory bowel disease. Amyloidosis,
      although rare, is life-threatening, especially when it involves the kidneys. It
      is important to recognize this complication, especially since colchicine has been
      proposed as a possible treatment.We present a 25-year-old female diagnosed at the
      age of 13 years with Crohn's disease with involvement of the terminal ileum and
      right colon. Surgery was performed because of inflammatory activity unresponsive
      to corticosteroid and immunosuppressive drugs. She subsequently presented
      nephrotic syndrome due to secondary amyloidosis, which responded well to
      colchicine treatment.

PMID- 11333658
TI  - [Treatment of non-parasitic splenic cyst with percutaneous injection of alcohol].
AB  - We report a case of a 12-years-old girl treated by percuta-neous injection of a
      splenic epithelial cyst. Indication was due to the gradual cyst's growth and pain
      in left hypocondrium. A percutaneous drainage under ultrasonographic view was
      performed with direct puncture technique, inserting a pigtail catheter into the
      cyst. After the total aspiration of the contrast, we injected sterile absolute
      alcohol for 20 minutes. Subsecuently, it was aspirated and the catheter was
      pulled-out. After a follow up period of more than 4 years, the cyst remains
      collapsed. There were no complications.

PMID- 11333659
TI  - [Gastritis caused by Helicobacter heilmannii (Gastrospirillum hominis). Report of
      3 cases].
AB  - Helicobacter heilmannii infection is rare. Its clinical picture is rather
      different from that caused by Helicobacter pylori: alterations in the gastric
      mucosa are milder and mainly located in the gastric antrum, and the frequency of
      erosions and ulcers is lower. It has been described in association with
      conditions similar to those related to H. pylori: peptic ulcer, chronic
      gastritis, gastric adenocarcinoma, intestinal metaplasia and MALT (mucose
      associated lymphoid tissue) lymphoma, although the incidence is lower. We
      describe three cases of gastritis caused by H. heilmannii, which we consider to
      be of interest because of the absence of cases published in Spain. One of the
      cases is especially unusual because of its association with a duodenal ulcer. We
      also describe the main features of H.r heilmannii. Its clinical treatment is
      similar to that used in H. pylori, with demonstrated morphological improvement of
      the lesions after eradication of the infectious agent.

PMID- 11333660
TI  - [Aquaporins and renal water metabolism. Role in the physiopathology of water
      retention in cirrhosis].

PMID- 11333661
TI  - [Complementary and alternative treatment to surgery in liver metastases of
      colorectal cancer].

PMID- 11333662
TI  - [Hirsutism, flutamide and hepatotoxicity].

PMID- 11333663
TI  - [Citrobacter freundii: a rare cause of spontaneous bacterial peritonitis].

PMID- 11333664
TI  - [Nimesulide-induced acute hepatitis].

PMID- 11333665
TI  - [Duodenal erosion as a complication of a Kehr T tube].

PMID- 11333668
TI  - [Long-term prognosis of childhood IgA nephropathy in adult life].
AB  - BACKGROUND: To evaluate long-term prognosis in a group of children with IgA
      nephropathy and to analyse which clinical factors were associated with
      progression to chronic renal failure in adulthood. PATIENTS AND METHOD:
      Retrospective study. 58 young adults with IgA nephropathy diagnosed at 10.6(SD
      2.9) years old and studied after a follow-up of 11.8 (SD 2.9) years. RESULTS:
      Relapses of macroscopic hematuria and proteinuria were the most frequent symptoms
      at onset (75.9%). In 25.9% of patients high plasmatic IgA levels were also
      detected. Most cases had grade I (44.8%)or grade II (44.8%) histological lesions
      at diagnosis. At the last control, clinical remision was observed in 21 patients
      (36.2%) and 50% of the whole group remained with abnormal urine. 8
      patients(13.8%) reached terminal renal failure. Mean renal survival (defined as
      glomerular filtration rate above 50 ml/min/1.73 m2)was 100, 93.3 and 81.1% at 5,
      10 and 15 years of evolution, respectively. CONCLUSIONS: About 14% of children
      with IgA nephropathy had long-term renal bad prognosis. Hypertension at onset,
      plasma creatinine elevation and proteinuria during adolescence were significant
      risk factors associated with chronic renal failure during adulthood. Minimal
      lesions at IgA nephropathy diagnosis in children did not exclude long-term poor
      prognosis.

PMID- 11333669
TI  - [Early diagnosis of retinoblastoma: usefulness of searching for RB1 gene
      mutations].
AB  - BACKGROUND: Retinoblastoma, the intraocular malignancy most common in
      children,occurs in both familial and sporadic (bilateral or unilateral).
      Hereditary predisposition is caused by a germ-line mutation while non-hereditary
      is due to two somatic mutations in a retinal cell. This work was carried out in
      order to analyse genetically, the high number of families with some affected
      member and to go deep into the molecular mechanisms responsible of this
      pathology. PATIENTS AND METHOD: 59 families with one or more affected members
      were analysed. Cytogenetics and with polymorphic markers studies were carried out
      and a search for mutations was performed in DNA from white cells and from
      available tumoral tissue. RESULTS: In four of the 5 familial cases, the
      responsible mutation was established,the same as in 9 of the 13 bilateral
      sporadic. In the 7% of the unilateral sporadic cases, mutation was found in
      leucocytary DNA. Lost of heterozygosity as a second mutational event was mainly
      due to mitotic recombination. CONCLUSIONS: Among the mutations of our series, a
      higher frequency of punctual mutations,responsible of the first mutational event,
      was observed at constitutional level. Lost of heterozygosity was the mechanism
      observed in the majority of the tumours.

PMID- 11333670
TI  - [IgA nephropathy].

PMID- 11333671
TI  - [Smoke blinds your mind].

PMID- 11333673
TI  - [Breast cancer in the Rubens and Rembrandt paints].

PMID- 11333672
TI  - [Sequential liver transplantation: description of the first three patients in
      Spain].
AB  - BACKGROUND: Domino or sequential liver transplantation (DTXL) is a kind of living
      donor transplant, which was proposed in 1993 and performed for the first time in
      1995; later on, more than 45 have been reported. The liver from a patient with
      familial amyloidotic polyneuropathy(FAP) is used to another patient aged more
      than 60 with hepatic disease generally cancer, because FAP livers are
      anatomically and functionally normal except for the synthesis of the systemic TTR
      variant which only could generate FAP in the recipient after more than 8 years.
      PATIENTS AND METHOD: The three first cases of DTXL performed in Spain are
      presented. The donors were FAPTTRMet30 patients from the Major can focus. The
      first recipient showed severe hyperinsulinism due to metastatic liver from
      malignant insulinoma; the others had hepatocellular carcinoma on a cirrhotic
      liver. RESULTS: During the post operatory period liver function of recipients was
      perfect,and hyperinsulinism disappeared in the first; this patient died after 10
      days by sepsis whereas the others showed normal liver function, no recurrent
      cancer nor onset of FAP. The donors outcome was normal with perfect liver
      function. CONCLUSIONS: Based on our results, in agreement with previous reports,
      we conclude that DTXH is valid procedure for a selected patient group. In
      addition they increase the pool of liver donors and therefore diminish the
      overloaded waiting lists.

PMID- 11333674
TI  - [Prenatal screening of congenital toxoplasmosis].

PMID- 11333675
TI  - [Current and future use of hemopoietic growth factors].

PMID- 11333676
TI  - [Reference values of body composition by bioelectrical impedance. Methodological
      remarks].

PMID- 11333677
TI  - [Treatment of visceral Leismaniasis in HIV patients with a new regimen of
      liposomal amphotericin].

PMID- 11333678
TI  - [On the likelihood ratio].

PMID- 11333681
TI  - [Antilipemic agents and evidence based medicine].

PMID- 11333683
TI  - [Risk factors for type 2 diabetes mellitus].

PMID- 11333686
TI  - [The prevalence of dementia and its main subtypes in subjects older than 65
      years: impact of occupation and education. The Toledo Study].
AB  - BACKGROUND: To assess the prevalence of dementia and its subtypes in a population
      with a low level of education, and to determine whether there is any association
      between occupation, education and dementia. SUBJECTS AND METHOD: Cross-section
      study of the population, with a sample of 3,214 individuals representative of the
      population of Toledo, Spain, aged 65 years and older. The Mini-Mental State
      Examination (MMSE) was used in the first phase of the study to detect those
      individuals with cognitive deterioration. The second phase consisted of a semi
      structured clinical interview and neuropsychological evaluation. Dementia and sub
      types of dementia were determined using well-established diagnostic criteria. The
      process was applied using an algorithm to optimise diagnostic agreement. RESULTS:
      The overall prevalence of dementia, Alzheimer's disease and vascular dementia
      amounted to 7.6, 4.6 and 1.8%, respectively. A direct relationship was detected
      between these three entities and age. The prevalence of dementia was greater in
      women, illiterate persons and occupations which require less skill. Once
      adjustment had been made for other socio-demographic variables, only age was
      associated with the presence of dementia. CONCLUSIONS: The overall prevalence of
      dementia, Alzheimer's type dementia and vascular dementia increases with age. No
      clear association was found between education, occupation and dementia.

PMID- 11333687
TI  - [Comparison of two models of education for asthmatic patients].
AB  - BACKGROUND: The education programs have demonstrated to be an important point in
      the management of asthmatic patients. The aim of the present study was to assess
      if an intensive group asthma education program was able to improve a simplified
      and individual asthma education program, both with a self-management plan
      included. PATIENTS AND METHOD: A prospective randomised controlled trial was
      conducted over 12 months and 73 moderate-severe asthmatic patients were included.
      Patients were randomly assigned to control or study group. Patients in control
      group received individual and simplified education with a self-management plan
      and patients in study group attended an <<asthma school>> in small groups where
      they received a three hours education program in three weeks.The outcome measures
      were: number of hospital admissions, observation unit admissions, emergency
      visits and unscheduled general practice consultations. Knowledge, adherence to
      treatment, ability with inhaler devices, airway function, environmental control
      measures and quality of life. They were assessed at the beginning and the end of
      the study. RESULTS: At the end of the study period the outcome of morbidity had
      improved in both groups but the number of observation unit admissions (p = 0.028)
      and unscheduled general practice consultations (p = 0.022) was substantially
      lower in study group. This group also demonstrated improvement in environmental
      control measures and better inhaler technique and knowledge (p = 0.007). In
      adherence, lung function or quality of life there were no differences between
      groups. CONCLUSIONS: In patients with asthma better results can be obtained with
      an intensive group asthma education program than with the individual and
      simplified program.

PMID- 11333688
TI  - [The impact of the implementation of staying in the United Kingdom for six months
      or more as donor exclusion criteria on the donor base of the Basque Country].
AB  - BACKGROUND: To reduce the risk of new variant Creutzfeldt-Jakob disease by blood
      products some countries exclude persons who have spent six months or more
      cumulatively in the United Kingdom as blood donors. METHOD: We asked our donors
      about this selection criteria to evaluate the loss of blood donors and donations
      in case of implementation of this measure. RESULTS: 11,681 donors and 1,648
      refused persons were analyzed. 123 (1.05%) and 11 (0.66%) respectively fulfilled
      this criteria. CONCLUSIONS: In case of implementation of this selection criteria
      1% of blood donors and 1.77% blood donations would be lost.

PMID- 11333689
TI  - [Prescription of generic pharmaceutic specialties in discharge reports at a
      university hospital].
AB  - BACKGROUND: The use of generic pharmaceutic specialities (GPS) has risen lately
      as a necessary tool in the control of sanitary expenses. This use is becoming of
      high importance, even in the non-medical media. Our aim was to stablish its use
      profile in patients discharged from a University Hospital. MATERIAL AND METHOD:
      To analyse the use of GPS in 256 discharge reports, randomly chosen from the
      Clinical Documentation Service, belonging to eight different Units for two months
      (June-July 2000). RESULTS: A total of 1233 prescriptions were reported. Among
      them, there was an equivalent generic drug to the medication prescribed in 220
      cases (18%), but only in five ocasions one of them was indicated (2.2%). The cost
      of the drugs with an equivalent form in GPS was calculated in 707,521 pts. This
      cost could have been reduced to 505,865 pts. taking into account the average
      price of the GPS. In case of indicating the cheapest one, the cost could have
      been 479,672 pts. CONCLUSIONS: There is an important proportion of GPS to
      indicate as an alternative to the usual medicaments prescribed. However,
      nowadays, the GPS prescription is not a usual practice among the hospital
      physicians.

PMID- 11333690
TI  - [Education, brain reserve, and risk factors for dementia and Alzheimer disease].

PMID- 11333691
TI  - [Prions and blood donation].

PMID- 11333692
TI  - [Is it possible to reduce the cost of clinical research of new drugs? Cooperation
      between the pharmaceutical industry and health care authorities].

PMID- 11333693
TI  - [A 33-year-old male infected by the human immunodeficiency virus with vomiting
      and abdominal pain of 15 days of duration].

PMID- 11333694
TI  - [Spontaneous bacterial peritonitis caused by Hafnia alvei].

PMID- 11333695
TI  - [Gynecomastia associated with the simultaneous use of cisapride and
      lansoprazole].

PMID- 11333696
TI  - [The evaluation process in the Fund of Health Research].

PMID- 11333697
TI  - [Confidentiality of family history].

PMID- 11333698
TI  - [Fatal infection by cytomegalovirus in a patient after splenectomy and
      transfusion following trauma].

PMID- 11333700
TI  - [Subclinical carotid atherosclerosis in patients with coronary disease].
AB  - BACKGROUND: B-mode ultrasonography is a simple and valid method to evaluate
      subclinical atherosclerosis of the major superficial arteries. The aim of this
      study was toknow by this technique the prevalence of carotid atherosclerosisin
      patients with coronary disease and related factors. PATIENTS AND METHOD: In
      232patients (205 men and 27 women; age: mean [standard deviation]59 [8] years)
      with coronary disease, intima-media thickness (IMT),presence and number of
      atheroma plaques in carotid arteries wereevaluated by B-mode ultrasonography.
      Controls were 50 healthy subjects whose age was not different from patients.
      Carotid atherosclerosis was considered when IMT was higher than mean plus two
      standarddeviations of control values, and/or existence of atheroma plaques.
      RESULTS: Carotid IMT wasincreased in patients compared to controls 0.82 [0.22] vs
      0.62[0.12] mm; p < 0.001) and there were more patients with plaques(67 vs 20%; p
      < 0.001). Carotid atherosclerosis was found in170 patients and 11 controls (73 vs
      22%; p < 0.001). By multivariate analysis, carotid atherosclerosis was associated
      with age (oddsratio: 1.05; 95% confidence interval [CI], 1.01-1.09) and
      smoking(odds ratio, 2.11; 95% CI: 1.04-4.26). The presence of more thanone plaque
      was associated with levels of low-density-lipoprotein(LDL)-cholesterol (odds
      ratio, 1.01; 95% CI, 1.00-1.02). CONCLUSIONS: In the patients with coronary
      disease, prevalence of subclinical carotid atherosclerosisis very high (73%), and
      it is associated with age and smoking. The advanced stage of atherosclerosis,
      evaluated by the existence of more than one plaque, is correlated with LDL
      cholesterol levels.

PMID- 11333701
TI  - [Protein-calorie malnutrition and lymphocytopenia as predictors of hospital
      infection in the elderly].
AB  - BACKGROUND: Clinical and epidemiological studies have established that
      malnutritionis a risk factor for infection in patients being submitted to
      surgery. To date no study has been carried out to establish the association
      between the nutritional condition and the incidence of hospital-acquired
      infections in patients in the medical area. We study the incidence of hospital
      acquired infections in the elderly in an attempt to determine the rate of this
      infection and its association with protein-calorie malnutrition. Another aim of
      this study has been to determine the predictive value of the parameters used to
      evaluate the patient's state of nutrition and immunity. PATIENTS AND METHOD: We
      included 240 patients over 64 years old, 118 males and 122 females, admitted to
      the medical area of a general hospital. The nutritional and immunity condition of
      the patients was evaluated through determinations of weight, height, body mass
      index, hypoalbuminemia and total lymphocyte count. The psichophisical degree of
      dependence was evaluated through of Norton scale. The details on the hospital
      infections came from a clinical and microbiological follow-up of patients, in
      accordance with the criteria of the Centers for Disease Control of Atlanta.
      RESULTS: The frequency of protein-calorie malnutrition was 12.5% and the
      accumulated incidence of hospital-acquired infections was 19.6%. Functional
      incapacity of the elderly prior to hospitalization (odds ratio,4.70; 95% CI: 1.1
      19.0) as well as the presence of certain extrinsicrisk factors (odds ratio, 2.35;
      95% CI: 1.1-5.1) were, in addition to hypoalbuminemia (odds ratio, 3.60; 95% CI:
      1.3-10.2) and lymphocytopenia(odds ratio, 2.67; 95% CI: 1.3-5.7), the independent
      variables that showed the most significant association with the incidence of
      hospital-acquired infections. CONCLUSIONS: The nutritional parameters associated
      with the immune system determinedgreater risk of hospital-acquired infections
      among elderly patients admitted to the medical area of a hospital. The initial
      evaluation of elderly patients hospitalitzed in accordance whit the
      psychophysical degree of dependence based on the Norton scale is useful to
      evaluate those patients who were at greater risk for hospital infections.

PMID- 11333702
TI  - [Smoking and subjective health in Spain].
AB  - BACKGROUND: To examine the relationship between smoking and subjective health in
      Spain. MATERIAL AND METHOD: Datacome from the 1993 National Health Survey.
      Analyses were performed with logistic regression, adjusting for the main
      confounding factors. RESULTS: Among those less than 25 years, there is a dose
      response relationship (p = 0.0001)between cigarette consumption and suboptimal
      health (fair, pooror very poor health). CONCLUSIONS: Smoking controlactivities
      should inform on the worse subjective health of youngsmokers, for whom other
      effects of tobacco smoking are less relevant because they appear to happen in the
      distant future.

PMID- 11333703
TI  - [Nephropathy, nycthemeral variability and pulse pressure in patients with type 2
      diabetes mellitus].
AB  - BACKGROUND: The loss of the blood pressure nictemeral rhythm and the elevated
      pulse pressure are considered independent cardiovascular risk factors that can be
      related with the microvascular damage of patients with type 2 diabetes mellitus.
      PATIENTS AND METHOD: We carried out an observational, tranverse study, of a
      population of patients with type 2 diabetes mellitus. The variables are
      calculated by means of 24 hour ambulatory registry of blood pressure. The results
      are compared with the diverse degrees ofnephropathy. RESULTS: A total of 61
      patients is studied; 31 have a behavior "non dipper". The "non dipper" proportion
      increased with the urinary albumin excretion (p = 0.024). The pulse pressure was
      higher inpatients with macroalbuminuria (p = 0.004). CONCLUSIONS: Theresults
      demonstrate a more frequent loss of the nictemeral rhythm and higher pulse
      pressure among the patients with type 2 diabetes mellitus and nephropathy.

PMID- 11333704
TI  - [Regarding the diagnosis of vitamin B 12 deficiency].

PMID- 11333705
TI  - [Knowledge, skills and aptitudes in healthcare management].

PMID- 11333706
TI  - [Cyclosporiasis: a clinical and epidemiological study in travellers with imported
      Cyclospora cayetanensis infection].
AB  - BACKGROUND: To assess the clinical and epidemiological characteristics of the
      enteritis produced by Cyclospora cayetanensis. PATIENTS AND METHOD: A
      microbiological, epidemiological and clinical protocol in travelers to tropical
      and temperate areas affected by travelers diarrhea (TD). RESULTS: C.
      cayetanenesis was isolated from 55 patients. 96% of them suffered TD. Persistent
      diarrhea (> 2 weeks) was present in 69% and weight loss > or = 3 kg in 38%. In
      36% of cases, TD began after returning from the trip. Although C. cayetanensis
      has a cosmopolitan distribution, it was mostly isolated from travellers to Latin
      America, the Indian subcontinent and South East Asia. In only five cases a
      potential risk factor was detected: strawberries (3), buffalo's milk (1) and
      marinated fish "ceviche" (1). CONCLUSIONS: C. cayetanensis is an emerging
      enteropathogen, isolated in 2-4% of Spanish travellers suffering from TD, and
      should be considered in the diferential diagnosis of this clinical entity.

PMID- 11333707
TI  - [New drugs of year 2000: the challenges of the clinic and the manager].

PMID- 11333708
TI  - [Treatment of lipodystrophy in patients with human immunodeficiency virus
      infection].

PMID- 11333709
TI  - [Impact of oral prophylaxis with quinolones on microbial agents isolated from
      blood cultures during febrile episodes in hematologic patients].

PMID- 11333710
TI  - [Incidence of diabetes mellitus among high-risk Spanish individuals].

PMID- 11333711
TI  - [Helicobacter pylori eradication: comments from the consensus].

PMID- 11333713
TI  - [Intestinal stenosis secondary to intestinal endometriosis].

PMID- 11333714
TI  - [Cutaneous adverse events related to simultaneous nevirapine treatment and
      pneumococcal vaccination in HIV-infected patients].

PMID- 11333716
TI  - [Clinical manifestations and prevalence of hypercoagulable states in patients
      with venous thromboembolic disease].
AB  - BACKGROUND: Blood flow stasis, an alteration in the coagulation process or
      endothelium injury the most common mechanisms involved in venous thromboembolic
      diseases (TED) and constitute the so-called hypercoagulable states (HS). The HS
      have been classified into two groups: primary and secondary and several of them
      can be measured. Our purpose was to investigate the prevalence in Spain of
      measurable HS in patients with venous TED and to know the clinical picture of
      pulmonary embolism in these patients. PATIENTS AND METHOD: Sixty of 175
      consecutive patients diagnosed with deep venous thrombosis and pulmonary embolism
      fulfilled criteria to study a HS. The study was performed 1 month after
      anticoagulant therapy was finished. RESULTS: Seventeen (28%) of the 60 patients
      had one HS that was a primary disorder in 14 and a secondary one in 3. The
      increase of PAI-1 level was the most common; recurrence of thrombotic events and
      familial history were frequent in these selected patients. CONCLUSIONS: The
      prevalence of hypercoagulable states in venous thromboembolic disease was high in
      this series. The clinical picture was similar to those to be expected and PAI-1
      was the most frequent marker of hypercoagulable states.

PMID- 11333717
TI  - [Influence of menopausal status in homocysteine plasma levels].
AB  - BACKGROUND: Some studies have found that postmenopausal women have increased
      plasma homocysteine levels while others do not. The aim of this study was to know
      if homocysteine levels are increased in Spanish postmenopausal women. PATIENTS
      AND METHODS: In 100 postmenopausal women (age: mean [SD] 56 [6] years)
      homocysteine, creatinine, folic acid, vitamin B12 and lipoproteins were
      determined. Controls were 50 premenopausal women (age: 29 [6] years), 50 men with
      similar age to postmenopausal women, and 50 men with similar age to premenopausal
      women. All the subjects of the study were healthy. RESULTS: Homocysteine
      concentrations were higher in postmenopausal compared with premenopausal women
      (8.6 [2.1]; 95% confidence interval [CI], 8.2-9.1 vs 7.7 [1.6]; 95% CI, 7.2-8.1
      micromol/l; p < 0.05), but were not different between both men groups.
      Hyperhomocysteinemia was found in 9 postmenopausal but in any premenopausal women
      (9% vs 0%; p = 0.03). Low density lipoprotein cholesterol values were higher (155
      [32]; 95% CI, 148-161 vs 111 [32]; 95% CI, 101-120 mg/dl; p < 0.05), and high
      density lipoprotein cholesterol lower (54 [12]; 95% CI, 52-57 vs 64 [18]; 95% CI,
      59-69 mg/dl; p < 0.05) in postmenopausal than premenopausal women. In
      postmenopausal women homocysteine levels were negatively associated with folic
      acid and positively associated with creatinine levels, but there was not
      association with age, vitamin B12 serum levels and lipoproteins. CONCLUSION: In
      postmenopausal women increased homocysteine concentrations, together with
      hypercholesterolemia, could contribute to the raise of their cardiovascular risk.

PMID- 11333718
TI  - [A population-based study of need for changes and continuing rates of
      antihypertensive drugs].
AB  - BACKGROUND: Antihypertensive drugs are frequently changed because of inefficacy
      and adverse effects. The aim of this study was to compare the incidence of
      changes of the new classes of drugs from the classical beta-blockers and
      diuretics. We also have calculated the probability of continuing with each class
      of drug. MATERIAL AND METHOD: Clinical reports of hypertensive patients of a
      general practice centre were examined. All changes of treatment and their causes
      were registered between october 1997 and september 1999. The incidences for
      global changes and also for intolerance and inefficacy changes were calculated
      for each drug. Relative risks for beta-blockers, diuretics, ACE inhibitors of
      anhidride carbonic enzyme and angiotensine II-receptor-antagonists were analized.
      The cumulated probability for continuing therapy was also studied. RESULTS: 27.6%
      out of 786 courses of treatment were changed, 51.4% due to intolerance and 29,8%
      due to inefficacy. The probability for continuing was 88% after 3 months, 81%
      after 6 months, 71% after one year and 54% after 2 years. The probability for
      discontinuing because of intolerance was higher in the first 3 months (51%), but
      afterwards it remained stable along the time. CONCLUSIONS: Antihypertensive drugs
      are discontinued more frequently than what it would be desirable and their
      continuing rates are low. Differences observed among each class of drugs are not
      argument enough for changing the general recommendation of using beta-blockers
      and diuretics as first choice drugs for initial treatment of hypertension.

PMID- 11333719
TI  - [Conversion to clinically definite multiple sclerosis after isolated spinal cord
      syndrome: value of brain and spinal MRI].
AB  - BACKGROUND: Isolated spinal cord syndrome might be due to a first episode of
      multiple sclerosis. The aim of the study was to determine the clinical usefulness
      and paraclinical characteristics and of spinal and brain MR imaging predicting
      conversion to clinically definite multiple sclerosis (CDMS) in patients with an
      isolated spinal cord syndrome. PATIENTS AND METHODS: We have evaluate thirty
      eight patients with isolated spinal cord syndrome. A clinical protocol, lumbar
      puncture, evoked potential and brain-spinal cord MRI were performed. RESULTS:
      Twenty two percent of the patients fulfilling brain MRI Paty criteria (p < 0.01),
      54.5% Fazekas (p = 0.007) and 80% of patients fulfilling Barkhof criteria (p =
      0.009) presented CDMS. The spinal MR imaging from CDMS patients was always
      abnormal, showing cervical and marginal location with a diameter < 2 cm.
      CONCLUSION: Brain MRI is strongly predictive of the risk of developing CDMS and
      spinal cord MRI may increase the sensitivity to detect conversion to CDMS.

PMID- 11333720
TI  - [Skin cancer in patients submitted to organ transplantation: a growing problem].

PMID- 11333721
TI  - [Katayama fever in Spanish tourists: analysis of 25 cases].
AB  - BACKGROUND: Awareness about the clinical presentation and the clinical and
      terapeutical management of acute schistosomiasis in the non immune traveller.
      PATIENTS AND METHOD: Febrile patients with epidemiological history of swimming in
      endemic areas. Prospective protocol 1984-1999. RESULTS: 21% of patients with a
      diagnosis of schistosomiasis developed the Katayamna syndrome. Nine patients had
      also a clinical picture of swimmer's itch dermatitis. Diagnosis was suspected on
      the basis of epidemiology, fever and eosinophilia. Diagnostic confirmation was
      established through serology in 10 cases and parasitology in 11. In 2 cases both
      methods were positive. CONCLUSIONS: Fever and eosinophilia after being exposed to
      infested waters should rise alarm on the syndrome. Availability of serological
      tests with an earlier positivization and badly needed at present. In Spain two
      trips, to Mali (Dogon country) and Uganda, are responsible for 75% of the
      infections. The subject should be introduced routinely in our travellers clinics.

PMID- 11333722
TI  - [Is chemoprophylaxis a good strategy for tuberculosis control?].

PMID- 11333723
TI  - [Clinical use and indications of endoscopic ultrasonography].

PMID- 11333724
TI  - [Infectious arthritis by Mycobacterium kansasii in a patient with human
      immunodeficiency virus].

PMID- 11333725
TI  - [Femoral aneurysm infected by Campylobacter fetus].

PMID- 11333726
TI  - [Endocarditis by Bartonella in a patient with human immunodeficiency virus
      infection].

PMID- 11333727
TI  - [Hyperinsulinemic hypoglycemia and nesidioblastosis in adults. An exceptional
      disease].

PMID- 11333728
TI  - [Therapeutic strategies in Helicobacter pylori infection].

PMID- 11333730
TI  - [Therapeutic control and quality of life in coronary artery bypass surgery
      patients].
AB  - BACKGROUND: Description of measures of secondary prevention and of health related
      quality of life one year after the intervention in patients undergoing coronary
      artery bypass surgery. PATIENTS AND METHOD: One year follow up prospective study
      in patients undergoing first coronary bypass surgery without associated
      procedures and aged less than 80 in public and private hospitals in Cataluna,
      Spain. RESULTS: 710 patients were included, 85.4% were men, and mean age was of
      63 years. When compared women and men, 74.8 vs 48.7% patients were diagnosed of
      hypertension, 70.2 vs 55% of hypercholesterolemia, and 42.3 vs 28.7% of diabetes
      (p < 0.01); on the other hand, 31.2% of men and 2.9% of women were active smokers
      (p < 0.01). After a year of follow-up, 7% of the total population remained
      smokers; a significant reduction of anti-anginal treatments and a significant
      improvement in health related quality of life were observed. Cholesterol lowering
      treatment in patients previously diagnosed of hypercholesterolemia increased
      significantly between hospital admission and one year after hospital discharged
      (from 44% at the beginning to a 58% at the year of follow up; p < 0.01).
      CONCLUSIONS: Patients undergoing coronary artery bypass surgery clinically
      improved one year after the intervention, improving also their health related
      quality of life. However, the percentage of smokers and the level of
      antihypertensive and lowering cholesterol treatment at the end of follow up
      suggest a suboptimal control of risk factor

PMID- 11333731
TI  - [Two-month results are predictors of outcome in a smoking cessation program].
AB  - BACKGROUND: The supportive smoking cessation counseling (SSCC) and nicotine
      replacement therapy (NRT) have been proved to be an effective aid to smoking
      cessation. The aim of this study was to determine whether the results obtained in
      a two-month treatment program to helping smokers quit by means of supporting
      smoking cessation counseling or nicotine replacement therapy included in the
      routine medical care, can be considered as predictors of success in the long term
      (one year). SUBJECTS AND METHOD: A longitudinal and prospective study has been
      carried out, being included in the program all smoker patients who went a primary
      or specialist unit (n = 357) during a six-month term. The SSCC was carried out in
      those patients with a low nicotine dependence (Fagerstrom test < 7) or those who
      had not got a preparation stage yet. The NRT was tested in those patients with
      high nicotine dependence (Fagerstrom >= 7). RESULTS: 32 patients (9%) of the 357
      did not turn up to the established controls,being thus considered as hopeless
      cases. The one-year study was completed by 177 patients in the SSCC group and 148
      in the NRTgroup. Abstinence had been achieved by 39.2% of the SSCC group and by
      36.2% of theNRT group 12 months later. Previously, in the SSCC group the observed
      abstinence after two months that the beginning of the program was 34% (27.4-40.7)
      and in the NRT group was 52.1% (44.5-59.8). The patients who were abstinents
      after two months of the beginning of the program were 19 times more likely to
      remain abstinent after a year (odds ratio, 19.4), showing in the SSCC group a
      sensitivity of 72.4% and a specificity of 90.7%, and in the NRT group the
      sensitivity was 93.2% and the specificity of 71.2%. CONCLUSIONS: The results
      observed after two months of the beginning of the program are predictors of
      outcome and can allow modify the therapeutic attitude with the aim of achieve
      best rates of success.

PMID- 11333732
TI  - [Evolution of white coat hypertension to sustained hypertension. One year follow
      up by ambulatory blood pressure monitoring].
AB  - BACKGROUND: To analyse the evolution of the white coat hypertension (WCH) to
      sustained hypertension, by means of ambulatory blood pressure monitoring (ABPM)
      during the first year after its diagnosis. SUBJECTS AND METHOD: A prospective
      study of cohorts was designed in La Orden Health Center of Huelva, Spain. 86
      individuals divided in two groups: a) group not exposed (GNE): 43 voluntary
      normotensives, and b) group exposed (GE): 43 individuals with WCH, defined as the
      blood pressure was superior or above 140 and/or 90 mmHg, respectively, with a
      mean diurnal ABPM below 135 and 85 mmHg in both cases. A ABPM was performed
      (Spacelabs 90207) at the beginning of the study, after 6 months and after 12
      months. The clinical and ambulatory blood pressure and the incidence of sustained
      hypertension by ABPM in the two groups were compared. Sustained hypertension was
      considered when the diurnal blood pressure was superior to 135 and/or 85 mmHg for
      SBP and DBP. RESULTS: At the end of the study, 82 patients were evaluate. The
      incidence of hypertension at 6 months of follow-up was of 4,76% (CI, 0-26.9) in
      GNE and 19.04% (95% CI, 0-42,6) in GE (RR: 3.8; 95% CI, 0.86-16.9) (p = 0.052).
      At one year of follow-up the incidence of hypertension in GNE was of 9.8% (95%
      CI, 0.31-1) as opposed to 46.3% (95% CI, 20.5-72.1) in GE (RR: 4.63; CI, 1.7
      12.4) (p = 0.001). CONCLUSIONS: The patients with WCH present a higher incidence
      of hypertension as compared to the normotensives, after 12 months of our follow
      up.

PMID- 11333734
TI  - [Smoking cessation: is it possible?].

PMID- 11333733
TI  - [Reduction of hematogenous infection in HIV positive patients following highly
      active antiretroviral therapy].
AB  - BACKGROUND: Bloodstream infections have probably decreased in HIV patients since
      highly active antiretroviral therapy (HAART) usage. PATIENTS AND METHOD:
      Hematogenous infections, including mycobacteria and fungi in HIV patients,
      stratified into two periods (I: 1995-1996 and II: 1997-1998) were included to
      evaluate changes attributable to HAART. RESULTS: 226 episodes were attended
      (incidence: 38.8 in period I and 15.3 in period II; p < 0.01). A significant
      decrease was observed in immunosuppression related microorganisms. HAART usage
      increased from 6.4% in period I to 31.2% in period II. Immunological parameters
      of HIV patients significantly improved in period II. CONCLUSIONS: Hematogenous
      infections have significantly decreased in HIV patients since the use of HAART.

PMID- 11333737
TI  - [Evidence-based clinical practice guidelines development. From the bottom, to the
      top].

PMID- 11333735
TI  - [Neurocysticercosis: an imported disease?].
AB  - BACKGROUND: Neurocysticercosis is the CNS involvement caused by Taenia solium
      larvae and the most frequent cerebral parasitation. It has a cosmopolitan
      distribution but endemic in the low income countries. The paper analizes the
      geographic origin, clinical characteristics of patients and the diagnostic and
      therapeutic modalities. PATIENTS AND METHOD: Retrospective revision of clinical
      files in patients with the diagnosis of neurocysticercosis between the period
      January 1990 to March 2000. RESULTS: Ten patients were included of which only one
      was of Spanish nationality. The others were immigrants or travellers to
      Central/South America (7), Africa (1) and South East Asia (1). Nine patients
      presented with convulsive crisis, generalized in 7 and 3 cases suffered
      headaches. The diagnosis was obtained through biopsy technique (3 cases) and the
      rest through CT scan or MR and serology. ELISA specific serology was positive in
      60% of cases. Eight patients were treated with praziquantel or albendazol solely
      with good clinical evolution. CONCLUSIONS: Neurocysticercosis is prevalent among
      the immigrant population and in our case imported mostly from Latin America.
      Diagnosis is reached through imaging and serological techniques. Treatment with
      praziquantel or albendazol improves the clinical picture and controls the
      convulsive crisis.

PMID- 11333738
TI  - [Recommendations on the multidisciplinary management in patients with malignant
      glioma].

PMID- 11333739
TI  - [Limitations of vital dye in selective biopsy of sentinel lymph node for
      melanoma].

PMID- 11333740
TI  - [Psoas abscess by Streptococcus agalactiae secondary to lumbar spondylodiscitis].

PMID- 11333741
TI  - [Intense muscle fatigue: an undesirable effect of beta blockers use in morbid
      obesity].

PMID- 11333742
TI  - [Spontaneous dissection of the cervical carotid artery].

PMID- 11333743
TI  - [Failure in the treatment of pulmonary hemorrhage associated with systemic lupus
      erythematosus].

PMID- 11333745
TI  - [Incidence and causes of sudden death in persons less than 36 years of age].
AB  - BACKGROUND: Epidemiological, clinical and pathological study of sudden death in
      children and young adults under 36 years old. SUBJECTS, MATERIAL AND METHOD:
      Sudden deaths between 1 and 35 years that occurred in Bizkaia (North of Spain)
      from 1991 to 1998 were analyzed. In all cases a complete forensic autopsy
      including histopathological, toxicological and occasionally microbiological
      studies were performed. Also, pathological antecedents were investigated.
      RESULTS: 107 sudden death cases between 1 and 35 years occurred, being the
      mortality rate of 2.4/100,000/year. Males were threefold at risk of sudden death
      than females. Mortality rate was higher in youngs than children. 4.5% of natural
      deaths were sudden deaths.43% were sudden cardiac deaths, and atheromatous
      coronary disease was the most frequent over 30 years. Myocardial diseases and
      conduction system abnormalities were common between 15 and 29 years. 39% were
      extracardiac sudden deaths. Infections were frequent in children, and epilepsy
      and asthma between 15 and 29 years. Intracraneal hemorrhage was also frequent. In
      19 cases (18%), specially in children, the cause of death was unexplained. Cause
      of death was different according to gender and age. CONCLUSIONS: Sudden death is
      infrequent in children and youngs, and causes are numerous. This study supports
      the importance of complete forensic autopsies in order to encourage
      epidemiological and preventive studies on sudden death.

PMID- 11333746
TI  - [Evaluation of dipstick for diagnosis of urinary tract infection in children and
      adults].
AB  - BACKGROUND: Dipstick is used as a first test for screening urinary tract
      infection. MATERIAL AND METHOD: 1087 urine samples from paediatric and adult
      patients were processed with dipstick and direct microscopic observation of
      pellet as well as of a Gram stain. A culture was also performed in all of them
      and was considered as the reference method in order to evaluate all other tests.
      RESULTS: Sensitivity of dipstick and of Gram stain was higher in urines from
      adults than in those from children, but direct examination of pellet was better
      in paediatrics. Specificity of the three screening tests previous to culture
      presented few variations in both groups. Predictive positive value of dipstick
      and direct pellet was slightly better in children's urines; on the contrary, Gram
      stain was better in adults. Negative predictive value was similar for the three
      parameters. CONCLUSIONS: The dipstick here evaluated is a good method for
      screening of urinary tract infection, though its positivity obliges to a
      bacteriologic follow up in order to get a certainty diagnosis. Nevertheless, in
      children less than 2 year old we recommend universal urine culture.

PMID- 11333747
TI  - [The effects of dust inhalation in slate industry workers].
AB  - BACKGROUND: Slate industries involve the risk of causing silicosis; these
      industries are now on the increase, which implies an increasing number of workers
      too. The effects of this type of mining on respiratory health are not yet known.
      SUBJECTS AND METHOD: A cross section study of active workers. Radiological and
      functional alterations, and their relation to risk factors, were assessed.
      RESULTS: A prevalence of 2.1% simple pneumoconiosis was found. The value of the
      FEV1 probed to be significantly related to smoking and to existence of nodulation
      of a 1/0 or higher profusion; these risk factors, when multiple regression is
      applied, work independently. CONCLUSION: Slate industry involves a risk of
      pneumoconiosis and other respiratory alterations.

PMID- 11333748
TI  - [Analysis of mutations A3243G, C3256T and mitochondrial deletions in 41 diabetic
      patients].
AB  - BACKGROUND: Mutations or deletions of mitochondrial DNA (mtDNA) define a new
      diabetes subtype. PATIENTS AND METHOD: The A3243G and C3256T mutations and mtDNA
      deletions were studied in 41 diabetic patients with maternally inherited diabetes
      mellitus or deafness. RESULTS: The A3243G mutation was found in one out of forty
      one diabetic patients (2.4%). Neither the C3256T mutation nor mtDNA deletions
      were detected. CONCLUSIONS: The search of A3243G mutation has to be considered in
      a diabetic patient with deafness and/or maternal history of diabetes.

PMID- 11333749
TI  - [Sudden death in young people].

PMID- 11333750
TI  - [Paradoxes in decision making at the end of life].

PMID- 11333751
TI  - [The ethics of prescriptions. Conflicts of the physician and the patient, the
      management entity and the pharmaceutical industry].

PMID- 11333752
TI  - [Sarcoidosis].

PMID- 11333753
TI  - [Sleep apnea syndrome as cause and consequence of congestive heart failure].

PMID- 11333754
TI  - [Ehrlichiosis infection prevalence in Spain or cross reactions].

PMID- 11333755
TI  - [Risk behaviours among intravenous drug users under methadone treatment].

PMID- 11333756
TI  - [Cytokines: how to translate into Spanish language?].

PMID- 11333757
TI  - [Hallucinatory delirium and psychomotor agitation as paradoxal manifestations of
      acute propoxyphene poisoning].

PMID- 11333758
TI  - ["Impoverished" research: cancer in NATO soldiers].

PMID- 11333759
TI  - [Osteitis fibrosa cystica].

PMID- 11333760
TI  - [Hormonal alterations on young morbid obese women].
AB  - BACKGROUND: Human obesity is a widespread disease with considerable variability
      as to its severity, metabolic and endocrine manifestations and etiology. In the
      present study we have determined whether the alterations of uncomplicated severe
      obesity in adult young women affect with different intensity the circulating
      levels of hormones that have been postulated to intervene in the development and
      maintenance of obesity. SUBJECTS AND METHOD: Age-matched 20 morbidly obese (BMI
      52.6 [8.3 SD] kg/m2) and 10 normal-weight control women (BMI 19.9 [2.1 SD]
      kg/m2)were studied and determined the basal circulating levels of hormones and
      proteins related with the control of body weight. RESULTS: Obese women showed
      higher concentrations of insulin and leptin, and lower of cortisol and cortisol
      binding globulin (CBG). No significant differences were appreciated for free
      thyroxine, TSH, free and acylestrone and dehydroepiandrosterone-sulphate.
      CONCLUSIONS: The results suggest that morbid obesity implies the alteration of
      the main hormonal systems controlling the availability of energy and the response
      to external challenges, with the noteworthy exception of the thyroid. There were
      clear alterations of insulin and leptin,but cortisol changes could be more
      related to factors other than obesity. The lower than expected levels of
      acylestrone point to a possible deficit of this ponderostat signal in obese
      women. The relatively young age of the women in the study may account for the
      relative shallowness of the hormonal changes observed.

PMID- 11333761
TI  - [Factors related to psychotropic drugs consumption among the Spanish adult
      population. Data from the Spanish National Health Surveys for 1993, 1995 and
      1997].
AB  - BACKGROUND: In this study, the aim is the identification of the factor associated
      with psychotropic drug use among the Spanish adult population. MATERIALS AND
      METHOD: A descriptive and cross-sectional survey is carried out using data from
      the Spanish National Health Surveys from 1993, 1995 and 1997. As subjects of the
      study we have chosen the spanish adult population (aged 16 plus). INDEPENDENT
      VARIABLES: socio-demographic factors and health profile. Dependent variables are
      the overall consumption of psychotropic drug, both prescribed and no prescribed.
      RESULTS: Prevalence of psychotropic drug consumption is higher among women (6.9%
      in 1993; 9.9% in 1995, and 9.7% in 1997) than among men (3.1% in 1993; 4.8% in
      1995, and 4.7% in 1997). According to multivariance analysis, alcohol consumption
      have negative association, anxiety or sleep disorder and depression seem to be
      strongly associated (OR = 22.44; CI 95%, 13.06-38.56 women, and OR = 42.97; CI
      95%, 17.69-104.40 men). CONCLUSIONS: Prevalence of psychotropic drug consumption
      is higher in women than in men. The most strongly associated variable is nervous
      or sleep disorder and depression.

PMID- 11333763
TI  - [Prevalence of hepatitis C virus infection in patients with non-Hodgkin's
      lymphoma].
AB  - BACKGROUND: To know the prevalence of HCV infection in patients diagnosed with B
      NHL in our area. PATIENTS AND METHOD: A group of patients diagnosed with B-NHL
      between 1998-99 were carefully reviewed (serological tests, HCV RNA, laboratory
      studies, toxicity, response to treatment and evolution) in a transversal study.
      RESULTS: Overall 9/77 (11.68%) of patients tested positive for HCV. Of the 9
      patients HCV(+) showed abnormal elevated trans aminases in opposition with 10.3%
      of patients that tested seronegative. CONCLUSION: Compared with normal
      individuals, we have seen a higher prevalence of HCV in our B-NHL patients. It
      may be possible that HCV play a role in that lymphoma's pathogenesis.

PMID- 11333762
TI  - [Prevalence of chronic hidden infections in a cohort of patients in substitutive
      treatment with methadone].
AB  - BACKGROUND: To analyse prevalence of hidden hepatitis B infection (HBV),
      hepatitis C virus (HCV), human immunodeficiency virus (HIV), and tuberculosis
      infection in drug users (DU) in a maintenance programme with methadone (MPM).
      PATIENTS AND METHOD: 189 DU were tested for HBV, HCV, HIV and tuberculin test.
      Drug addition history and route of administration were evaluated. RESULTS:
      Prevalence of HIV, HCV, and tuberculous infection was 29.2%, 75.9% and 59.3%
      respectively. Intravenous route, early use of heroin and delay to enter in MPM
      were significatively associated with HIV and HCV infections. CONCLUSIONS: There
      is a high prevalence of tuberculous and HCV infections in DU. Early access to MPM
      could decrease prevalence of those infections.

PMID- 11333764
TI  - [A "happy world"].

PMID- 11333765
TI  - [Non-Hodgkin's lymphoma and hepatitis C virus].

PMID- 11333766
TI  - [Results of treatment with 2-chlorodeoxyadenosine in refractory or relapsed
      Langerhans cell histiocytosis. Study of 9 patients].
AB  - BACKGROUND: To analyse the results of the treatment with 2-chlorodeoxyadenosine
      (2CdA) in 9 patients with refractory or relapsed Langerhans cell histiocytosis
      (LCH) tracted in 8 Spanish hospitals between 1993 and 1999. PATIENTS AND METHOD:
      In the 9 patients the following data were recorded: age, sex, organ involvement
      by LCH, first treatment and response, dose, number of cycles and schedule of
      administration 2CdA, response to 2CdA treatment, toxicity, disease-free survival
      (DFS) and overall survival (OS). RESULTS: Median age was 25 years (range, 6-63).
      All patients had multiorganic involvement by LCH, with severe organ dysfunction
      in 4. 2CdA was administered as second line treatment in 7 cases and as third line
      in 2. The 2CdA dose was 0.1 mg/kg per day during 5 days in the majority of
      patients, and interval between cycles was 4 weeks. In 2 cases a complete
      remission (CR) was achieved and 4 cases attained a partial remission (PR)
      (overall response rate 66%). The main toxicity was hematologic, with neutropenia
      grade > 2 in 5 cases and thrombocytopenia > 2 in 5. Four patients had infections,
      with fatal evolution in one of them. After a median follow-up of 8 months (range
      2-17), 2 patients remained in CR (12 months both), 4 in PR (range 2-12 months)
      and one had active disease (17 months). The other two died due to progressive
      disease and Aspergillus spp. sepsis, respectively. The actuarial probabilities of
      DFS and OS were 58% (95% CI, 38-78%) and 71% (95% CI, 54-88%), respectively.
      CONCLUSIONS: 2CdA is an active drug for patients with refractory or relapsed LCH,
      and its main toxicity is myelosuppression. The usefulness of 2CdA, isolated or in
      combination with other drugs, in patients with refractory or relapsed LCH must be
      assessed in controlled studies.

PMID- 11333767
TI  - [Limitations of evidence-based medicine: the case of stroke].

PMID- 11333768
TI  - [Allergic conjunctivitis: clinical types and therapy].

PMID- 11333769
TI  - [Occupational asthma caused by persulphates: limited usefulness of the
      measurement of peak respiratory flow at the work place].

PMID- 11333770
TI  - [Familial isolated hyperparathyroidism].

PMID- 11333771
TI  - [Non reversible lithium neurotoxicity: a case report].

PMID- 11333772
TI  - [Primary thyroid lymphoma with bone marrow and central nervous system
      infiltration at presentation].

PMID- 11333773
TI  - [Inflammatory pseudotumor of the liver presenting as fever of unknown origin].

PMID- 11333774
TI  - [Extrinsic allergic alveolitis due to exposure to esparto dust].

PMID- 11333776
TI  - ?

PMID- 11333777
TI  - [In memoriam. Jean Lapresle].

PMID- 11333778
TI  - Molecular and anatomical studies in Alzheimer's disease.
AB  - This chapter builds on the themes developed during the last 10 years of studying
      the neuroanatomical basis of Alzheimer's disease (AD) from a neural systems
      perspective. Indirect evidence suggests that Abeta deposits are a dynamic lesion,
      and that a subset of Abeta deposits that stain for thioflavine S (thioS) are a
      critical lesion in terms of effects on neurons and their processes. Parallel
      studies in transgenic mice point to the same conclusion. Finally, we will discuss
      recent studies, using a remarkable microscropy tool that we have developed -an
      application of multiphoton microscopy- for in vivo histology, and in vivo
      functional imaging in living, anesthetized transgenic mice. Resolution is well
      below a micrometer, and cortical depths up to approximately 300 microns beneath
      the skull can be imaged; the mice recover uneventfully and can be reimaged days
      to months later. With this new technique, we can, for the first time, study
      dynamic processes of A beta deposition and resolution in a living brain.

PMID- 11333779
TI  - [Neuroimaging study with morphometric analysis of hereditary and idiopathic
      ataxia].
AB  - BACKGROUND: Hereditary and idiopathic ataxias are neurodegenerative disorders
      affecting diverse neuronal systems, particularly the cerebellum and its tracts.
      They are currently classified according to clinical and genetic criteria.
      Neuroimaging is a useful tool to help diagnosis but studies using quantitative
      methodology are scarce. OBJECTIVE: To apply digital morphometry to cerebral MRI
      and define objective patterns for clinical evaluation and follow up. PATIENTS AND
      METHODS: The study was carried out on 48 patients of whom 17 were Friedreich
      ataxia (FA), 6 non-Friedreich early onset spinocerebellar ataxia (EOCA), 9
      autosomal dominant cerebellar ataxia type 1 (ADCA 1), 7 ADCA 3 and 9 idiopathic
      late onset cerebellar ataxia (ILOCA); 35 controls were grouped on early (< 30
      years-old) and late age. Morphometric measures were done on previously selected
      MRI planes by image analyser digital software. RESULTS: Six out of 21
      measurements and 3 ratios were significantly discriminant. By categories, the
      structures mainly involved were as follows: atrophy of cervical spinal cord (p =
      0.001), cerebellum (p = 0.038) and protuberance (p = 0.002) in FA; atrophy of
      spinal cord (p = 0.009), cerebellum (p = 0.035) and widening of IV ventricle (p =
      0.044) in EOCA; shrinkage of protuberance (p = 0.009), middle cerebellar
      peduncles (p = 0.004) and spinal cord atrophy (p = 0.001) in ADCA 1; cerebellar
      atrophy (p = 0.041) in ADCA 3; and cerebellar atrophy (p = 0.041) and shortening
      of middle cerebellar peduncles (p = 0.038) in ILOCA. CONCLUSIONS: This
      quantitative morphometric study confirms the existence of different pattern of
      cerebral involvement that is closely related with the distints clinical forms of
      hereditary and idiopathic ataxias. Only a few measurements can be used to obtain
      a morphometric profile for diagnostic and follow up purposes.

PMID- 11333780
TI  - [Neurologic complications of herpes zoster. A retrospective study in 100
      patients].
AB  - INTRODUCTION AND OBJECTIVES: The neurologic complications associated with herpes
      zoster are infrequent except for postherpetic neuralgia. The aim of this study
      was to review the clinical profile and the distribution of these complications in
      a retrospective series of patients. PATIENTS AND METHOD: A retrospective analysis
      of the last 100 patients admitted with the diagnosis of herpes zoster with
      neurologic complications to our center from 1992 to 1999 by the Departments of
      Internal Medicine and Neurology was performed. The characteristics of the
      complications other than postherpetic neuralgia are reported. RESULTS: Aside from
      the 88 patients with postherpetic neuralgia, the 12 remaining patients presented
      other complications: seven different peripheral neuropathies, including three
      with Ramsay-Hunt syndrome, two meningitis, one encephalitis and one myelitis. In
      addition, one patient had ophthalmic herpes zoster with cerebral vasculopathy as
      ipsilateral Wallenberg's syndrome. Nine patients (75%) were males, four (25%)
      were under the age of 20 years and seven older than 60 years and only three were
      immunodepressed. The CSF was abnormal in six out of the eight patients in whom it
      was studied with lymphocytic pleocytosis being shown on analysis without
      qualitative or quantitative alteration in intrathecal synthesis of IgG. In the
      immunosuppressed patients the serology in the CSF of the varicela zoster virus
      was negative. All patients demonstrated regressive evolution following treatment
      with acyclovir. CONCLUSIONS: Neurologic complications other than postherpetic
      neuralgia occurred in 12% of the patients of this series, there was male
      predominance and peripheral neuropathies were the most frequent complications.
      Serology of the varicela zoster virus in immunosuppressed patients may be
      negative. In this series the prognosis was mainly satisfactory.

PMID- 11333781
TI  - Santiago Ramon y Cajal.
AB  - We carry out a brief review of Santiago Ramon y Cajal's life. Cajal was born on 1
      May 1852 in Petilla de Aragon (Spain) and died on 17 October 1934 in Madrid. He
      graduated in medicine at the University of Saragossa in 1873 and successively
      occupied the chair of Anatomy in Valencia (1884-1887), and Histology and
      Pathology in Barcelona (1888-1891) and Madrid (1892-1922). Starting from the
      modified Golgi staining method applied to embrions or young animals, Cajal
      published a monumental histology of the nervous system creating the revolutionary
      concept of the neuron doctrine and dynamic polarization of the neuron. He also
      introduced new staining methods including reduced silver nitrate, formol-urano
      and sublimate gold. He then procceded to study the process of degeneration and
      regeneration of the nervous system and the fine texture of the neuron and
      neuroglia. Together with Golgi, Cajal was awarded the Nobel prize for Physiology
      and Medicine in 1906. Don Santiago was also an excellent teacher, painter,
      photographer and writer. He is the greatest of all Spanish scientists, the most
      cited classical scientist and the chief architect of the neuron theory.

PMID- 11333782
TI  - [Oncolytic adenovirus for the treatment of cerebral tumors: past, present and
      future].
AB  - The transfer of genetic material as a therapy (gene therapy) is one of the
      experimental treatments being considered in patients with brain tumors resistant
      to any conventional treatment. Several clinical trials have proved that the
      intratumoral administration of genes is fairly safe for patients, however the
      anti-tumor effect of these strategies remains suboptimal. One of the main
      problems in cancer gene therapy is the failure of current vectors to achieve
      enough tumor transduction in a suficient number of cells. This is even true for
      vectors derived from viruses with high infectivity ability such as adenovirus.
      For that reason, current strategies explore the use of adenoviruses able to
      replicate and spread throughout the tumor. The local, intratumoral injection of
      adenovirus is an especially suitable strategy for gliomas because these tumors,
      although infiltrative, rarely metastasize. Two approaches have been used to
      generate tumor-selective replicative adenoviruses: use of tumor-specific
      promoters to regulate the expression of viral genes, and the deletion of the
      viral functions required for the activation of the cell cycle. Since normal cells
      surrounding giomas are quiescent, the second strategy is particularly attractive
      to develop new treatments for brain tumors.

PMID- 11333783
TI  - [Carcinomatous encephalitis or intracerebral miliary metastasis].

PMID- 11333784
TI  - [Kinesigenic paroxysmal choreoathetosis: contribution of SPECT].
AB  - We report two unrelated patients affected of kinesigenic paroxysmal
      choreoathetosis (CPC), during a symptomatic period. Routine complementary exams
      were normal. The 99mTc-HMPAO cerebral SPECT showed hyperactivation in the basal
      ganglia opposite to the choreoathetosic symptoms and reduced untake in the near
      parietal and subcortical zones in one case. These observations suggest that
      abnormal hyperactivity of contralateral basal ganglia may cause choreathetotic
      movements in patients with CPC.

PMID- 11333785
TI  - [Peripheral neuropathy associated with intestinal inflammatory disease].
AB  - The association of outlying peripheral neuropathy and inflammatory bowel disease
      is a rare fact leaving aside factors like the deficit of intestinal absorption of
      vitamins or the neurotoxicity of drugs employed for the treatment of the
      inflammatory bowel disease. We presented a series of four patients with this
      association, to whom a retrospective study was carried out. In all cases
      polineuropathy followed a course parallel to the inflammatory bowel disease,
      being acute and reversible in two cases. The polyneuropathy could be attributed
      to a deficit of vitamin B12 in one case and to metronidazole neurotoxicity in the
      other; in the remaining two cases the polineuropathy was chronic and no
      etiological factor could be found except for the own activity of the inflammatory
      bowel disease. We think that the neuropathy can represent a rare extraintestinal
      manifestation of the illness with a common autoimmune pathogenic mechanism. In
      one of our cases, the nerve biopsy demonstrated an axonal neuropathy with an
      alteration of the epineural vessels which showed a healed aspect.

PMID- 11333786
TI  - [Adult polyglucosan body disease: report of one case].
AB  - Adult polyglucosan body disease is a recently established clinicopathological
      entity, with few cases reported in the literature. In this paper we describe a
      case of a 46-year-old man who had died to a pancreatic cancer whose
      neuropathological study revealed a massive accumulation of polyglucosan bodies in
      the cerebral white matter, brainstem, cerebellum and spinal cord consistent with
      the adult polyglucosan body disease. We also discuss the pathological criteria
      used to differentiate this disease from others in which polyglucosan bodies may
      accumulate in the nervous system.

PMID- 11333787
TI  - [Hypoglossal nerve paralysis secondary to metastatic hepatoma].

PMID- 11333788
TI  - [Peripheral neuropathy in POEMS syndrome. Prognosis implications of an early
      diagnosis].

PMID- 11333791
TI  - ?

PMID- 11333792
TI  - [Perioperative transfusion medicine].

PMID- 11333793
TI  - [Expected versus real impact factors of publications from Spanish departments of
      anesthesiology (1991-1996)].
AB  - OBJECTIVE: To identify publications by Spanish anesthesiologists in journals
      indexed by Journal Citation Report from 1991 through 1996; to count the number of
      citations received and compare the results with the impact factor (IF) of the
      journals in which they were published. MATERIAL AND METHODS: Articles for which
      the first author was a member of a Spanish anesthesiology department were
      searched for in MEDLINE, Science Citation Index and EMBASE. Only publications for
      which the IF was known were included for analysis. We then counted the number of
      citations each article received over the two years following publication,
      recording the source journal in which the citation appeared and country of origin
      of each citing author. We then calculated the real IF (RIF) of each article, the
      RIF of all the Spanish articles, and the mean RIF. Also calculated for each
      article was the expected IF (EIF), based on the IF of the source journal, the
      overall EIF and the mean EIF. RESULTS: One hundred seventy-two articles were
      published; 49 of them were letters to the editors. Specialist anesthesiology
      journals published 72.7%. A total of 186 citations were received. American
      authors cited the articles more often than did other Spanish authors. Thirty
      seven citations (19.9%) were self-citations. Ninety-two articles (53.5%) were
      never cited. With letters to the editor excluded, the RIF was 85.48 and the
      global EIF was 213.28; the mean EIF was 1.734 and the RIF was 0.695. Therefore,
      the rate of citation of the Spanish authors in the period studied was only 40% of
      the citation rate of the entire population of authors from all countries. The
      authors of the published articles worked mainly in hospitals in Barcelona,
      Madrid, La Coruna, Valencia, Cantabria and Murcia. Hospital Germans Trias i Pujol
      (Badalona, Barcelona) had the largest number of publications and the highest EIF
      (39.41). Hospital del Mar (Barcelona) had the highest mean RIF and the highest
      global RIF.A gradual increase in the annual productivity of Spanish scientists
      can be discerned in a progressive increase in the number of publications as well
      as their EIF and RIF. CONCLUSIONS: Research by Spanish anesthesiologists is
      concentrated in only a few hospitals. Although the number of publications is
      increasing, their international repercussion has still not reached the desired
      level.

PMID- 11333794
TI  - [Spinal anesthesia: a protective factor in thromboembolic disease. A
      retrospective cohort study of 484 arthroplasties].
AB  - OBJECTIVES: To compare general and spinal anesthesia in the context of
      thromboembolic disease after orthopedic surgery in patients receiving
      prophylactic therapy with low molecular weight heparins. PATIENTS AND METHOD: Of
      the 484 arthroplasties studied retrospectively, 209 involved total hip
      prostheses, 111 partial hip prostheses and 164 total knee prostheses. Spinal
      anesthesia (epidural or subarachnoid) was provided in 328 cases and general
      anesthesia in 156. Thromboembolic disease was diagnosed if the patient presented
      a compatible clinical picture or if there was confirmation by Doppler
      ultrasonography and/or venography for deep venous thrombosis or by scintigraphy
      for pulmonary embolism. Related factors studied were age; weight; prior fractures
      of the lower extremity; a history of thromboembolism, diabetes, high blood
      pressure or heart disease; and medication. RESULTS: Twenty-one patients
      experienced thromboembolic complications, 12 after general anesthesia and 9 after
      spinal anesthesia, the incidence in the latter being significantly lower (p <
      0.01, odds ratio 3.23, 95% CI). Multivariant analysis also showed a significant
      increase in thromboembolic disease (p = 0.05) among patients over 70 years of age
      (odds ratio 2.67, 95% CI). CONCLUSIONS: Spinal anesthesia provides some
      protection against thromboembolic disease in arthroplasty. Age is a risk factor.

PMID- 11333795
TI  - [The effect of anesthetic technique on recovery from neuromuscular blockade with
      cisatracurium].
AB  - OBJECTIVES: To assess the effect of four anesthetic techniques on recovery after
      a single dose of 0.2 mg/kg of cisatracurium. PATIENTS AND METHOD: After giving
      informed consent, 96 patients of both sexes, ASA I-III, were enrolled. Anesthesia
      was induced with fentanyl, propofol O2-N2O (FiO2 40%) after which the patients
      were randomly assigned to four groups according to maintenance technique:
      propofol by infusion, sevoflurane, desflurane or isoflurane at 1.3 MAC.
      Neuromuscular block was monitored (electromyographic recording of the pollicis
      adductor). Variables recorded were time of maximum block, duration of action of
      1% and 25%, and recovery indices at T0-TR75 andT25%-T75%. ANOVA was performed ( =
      0.05 and beta = 0.1). RESULTS: The groups were homogeneous. Time until recovery
      of 25% of baseline amplitude of the first response to a train of four (TOF) (T1)
      was longer in the desflurane group (68.4 +/- 11.1 min) than in the propofol group
      (60.2 +/- 9.4 min; p < 0.05). Time until recovery of 75% of the TOF-ratio was
      longer in the sevoflurane (96.8 +/- 13.1 min), desflurane (101.5 +/- 14.4 min)
      and isoflurane (94.1 +/- 13.9 min) groups than in the propofol group (83.7 +/-
      1.3 min) (p < 0.0001). Times until recovery of T1 up to 1% were not statistically
      different: 45.8 +/- 10.7 (propofol), 50.6 +/- 11.0 (sevoflurane), 51.3 +/- 11.5
      (desflurane) and 46.5 +/- 11.2 min (isoflurane). The 25% - 75% recovery index was
      also similar at 19.0 +/- 9.3 (propofol), 20.0 +/- 5.1 (sevoflurane), 25.7 +/-
      12.4 (desflurane) and 20.9 +/- 7.9 (isoflurane). CONCLUSIONS: The inhaled
      anesthetics studied prolong the duration of clinical effect of cisatracurium more
      than does propofol.

PMID- 11333796
TI  - [Autotransfusion after cardiac surgery. Hematological, biochemical and
      immunological properties of shed mediastinal blood].
AB  - OBJECTIVE: Although it is well documented that the reinfusion of unwashed shed
      blood reduces postoperative homologous blood requirements after cardiac surgery,
      the efficacy and safety of the technique has been questioned on the basis of
      several possible adverse effects. We therefore aimed to evaluate the extent of
      mediastinal shed blood damage by cardiopulmonary bypass (CPB) and extravasation.
      PATIENTS AND METHOD: Five perioperative blood samples were obtained from each of
      the 20 patients undergoing cardiac surgery: by venipuncture, during the induction
      of anesthesia (sample 1), at the end of CPB (sample 2), and one hour after
      mediastinal shed blood reinfusion (sample 5), and from the cardiotomy reservoir
      at the first and sixth postoperative hours (samples 3 and 4). Hematological,
      biochemical and immunological parameters, and the metabolic and functional status
      of shed erythrocytes were studied in each sample. RESULTS: Hematological and
      biochemical values were lower at the end of CPB and in shed blood, but not after
      reinfusion. Inversely, plasma free hemoglobin levels and echinocyte formation
      were elevated after CPB and in shed blood, the latter correlating with the
      decrease in serum albumin levels due to hemodilution. No alterations were
      detected in erythrocyte median corpuscular fragility, D-glucose, L-phenylalanine
      and L-serine uptakes or 2,3-bisphosphoglycerate content. Plasma IL-10 levels were
      elevated at the end of CPB, whereas shed blood showed increased levels of IL
      1beta, IL-6 and IL-10. Shed blood retrieval did not modify the pattern of
      circulating cytokines found at the end of CPB. CONCLUSIONS: Shed mediastinal
      blood salvaged after cardiac surgery seems to be an excellent source of red
      cells, which conserve functional and metabolic status; once reinfused, shed blood
      does not modify the inflammatory response of the patient to CPB.

PMID- 11333797
TI  - [Autotransfusion after orthopedic surgery. Analysis of quality, safety and
      efficacy of salvaged shed blood].
AB  - A series of immunosuppressant mechanisms can manifest during surgical procedures,
      mediated by immune system cells or by humoral factors, to which the
      immunosuppressant effects of anesthesia or blood transfusion may be added,
      possibly further prejudicing the patient's immunological status, having important
      clinical repercussions such as increased incidence of postoperative infection or
      tumor reappearance. Autotransfusion of various types is an effective alternative
      to homologous transfusion as the former avoids immunodepressant effects.
      Preoperative autotransfusion [preoperative donation of autologous blood (PTAB)]
      has been shown to be one of the safest and most effective techniques and is the
      gold standard for autotransfusion. Problems of over collection, anemia and over
      transfusion that sometimes occur with PTAB can be solved with better screening
      procedures. Intraoperative autotransfusion (IAT) and postoperative
      autotransfusion (PAT) avoid such problems completely. However, IAT is only cost
      effective in certain procedures (bleeding > 1,000-1,500 mL) and is not applicable
      in others, such as knee arthroplasty. PAT, on the other hand, in addition to
      being a good complement to other autotransfusion methods, may be the technique of
      choice in some procedures, such as knee arthroplasty, particularly if PTAB is
      contraindicated or if it is logistically difficult for a hospital to
      provide.However, in spite of its demonstrated efficacy, PAT of filtered blood has
      many critics, who warn of possible side effects and recommend the use of washed
      blood, which would make the procedure enormously more expensive unless it is
      performed with the same equipment used for IAT. Therefore, this review will
      analyze the hematologic characteristics of filtered blood, including metabolic
      status and survival of red blood cells, the components of the hemostatic system
      and inflammatory mediators, the content of fat particles and the possibility of
      their clearance, the incidence of infections and the dissemination of tumor
      cells. This analysis can reach the conclusion that salvaged filtered blood is a
      source of red blood cells of sufficient quality to be safely reinfused and that
      their reinfusion contributes significantly to reduce the need for homologous
      blood.

PMID- 11333798
TI  - [Systemic lupus erythematosus in the pregnant patient. Implications for
      anesthesia].
AB  - A 28-year-old woman with systemic lupus erythematosus and a history of aseptic
      meningitis, digestive bleeding due to thrombopenia and deep venous thrombosis
      underwent elective cesarean for transverse presentation at 35 weeks. Preoperative
      blood work-up showed an antinuclear antibody titre that was slightly positive and
      steroid treatment was started. Surgery operation was performed with general
      anesthesia. The outcome was satisfactory even though serious complications can
      develop during the management of anesthesia in such patients. Systemic lupus
      erythematosus is a chronic, multisystemic disease that mainly affects women of
      childbearing age. Antibodies and immunocomplexes play a fundamental role. Given
      the multiorgan involvement in this disease, preoperative study of the lupus
      patient should assess all such involvement, including maternal-fetal risk, as
      well as consider the drug and anesthetic management to be applied. Among the
      clinical signs that can affect management of anesthesia are the following:
      aseptic meningitis, high blood pressure, pericarditis, pneumonitis and recurrent
      venous thrombosis. Anemia, thrombopenia and significantly altered coagulation
      events are common.

PMID- 11333799
TI  - [Reimplantation edema in the transplanted lung. Reperfusion-ischemia or
      hydrostatic edema?].
AB  - The development of non cardiogenic pulmonary edema or pulmonary reimplantation
      response after lung transplantation has been well described. The cause is
      ischemic vascular injury of the allograft, results in increased permeability of
      the lung after reperfusion, in turn leading to interstitial and alveolar edema.
      We report two cases of pulmonary reimplantation response after bilateral
      sequential lung transplantation. Massive pink frothy fluid was noted in the
      orifice of the double-lumen endobronchial tube. Blood and endobronchial fluid
      samples were collected for protein electrophoresis. We conclude that, in spite of
      the severity of reimplantation response, this complication can be resolved early
      when the cause is mainly hydrostatic.

PMID- 11333800
TI  - [Tension pneumothorax during removal of a foreign body from the esophagus].
AB  - Extracting foreign bodies from the esophagus is a common procedure in emergency
      rooms. We report the case of an 82-year-old man who came to the emergency room
      after swallowing a clam shell. After three successive examinations by fiberoptic
      endoscopy, the last of which was performed with general anesthesia, the patient
      suffered pneumomediastinum and pneumothorax first on the right side and then,
      within a few hours, on the left. After extraction of the foreign body, bilateral
      pleural drainage and emergency repair of esophageal perforation were required.
      Episodes of pneumothorax have been described after endoscopic procedures on the
      digestive tract such as esophagoscopy. The cause of esophageal perforation
      described may be iatrogenic, produced during esophageal manipulations or it may
      be caused by the foreign body itself, by an awake patient's performance of
      Valsalva maneuvers during esophagoscopy, or the entrance of air in the pleural
      cavity through esophageal perforation; any of these would explain the
      presentation of pneumothorax in this case. In the presence of sudden
      cardiorespiratory deterioration in a patient undergoing an endoscopic procedure,
      a diagnosis of tension pneumothorax must be considered.

PMID- 11333801
TI  - [Epiglottitis after tracheal intubation in an immunosuppressed patient].

PMID- 11333802
TI  - [Decreasing iatrogenic complications during internal jugular vein catheterization
      by using a shorter guide needle].

PMID- 11333803
TI  - [General anesthesia in a pregnant patient with Friedreich's ataxia].

PMID- 11333804
TI  - [Utility of diagnostic protocols in perioperative allergic reactions].

PMID- 11333805
TI  - [Reflections on consultation in anesthesiology].

PMID- 11333806
TI  - [Factors affecting postoperative pain].
AB  - OBJECTIVE: To determine the influence on the intensity of postoperative pain of
      the following variables: sex, age, type of surgery, surgical approach, anesthetic
      technique and analgesia administered. PATIENTS AND METHODS: Six hundred twenty
      three hospitalized patients were enrolled from the units of general and digestive
      surgery, gynecology and obstetrics, ophthalmology, otorhinolaryngology,
      traumatology and orthopedics, and urology. Pain intensity was measured on a
      visual analog scale (VAS) when the patient left the post-anesthesia recovery ward
      (PARU) and 24 and 48 h after surgery, and on a verbal evaluation scale (VES)
      during the first and second days after surgery. RESULTS: Gynecology is the
      department where the most pain is reported, both when the patient leaves the PARU
      (>= 4 for 56.6% of patients) and during the first day on the ward (71.3% of
      patients suffer pain of moderate or high intensity). The correlation of pain with
      duration of procedure was strongest in the urology and surgery units, with common
      variances of 32.3% and 23.4%, respectively. More pain is felt during open
      procedures in the traumatology and urology units, which is not the case in
      gynecology and surgery. Patients receiving general anesthesia leave the PARU with
      pain at 3.4 +/- 1.8 cm on the VAS scale, versus 1.3 +/- 1.6 cm for patients
      receiving locoregional anesthesia. Patients who received only ketorolac for pain
      in the PARU generally experienced less intense pain (2.5 +/- 2.0 cm) than did
      those who received metamizol (3.3 +/- 1.5 cm), morphine (4.0 +/- 1.8 cm) or
      tramadol (4.5 +/- 1.8 cm). CONCLUSIONS: Surgical department, surgical approach,
      anesthetic technique and, finally, analgesic administered are the factors that
      determine the intensity of postoperative pain. These factors should therefore be
      taken into account when establishing treatment protocols to assure adequate
      control of postoperative pain. Neither sex nor age were determining factors for
      the intensity of postoperative pain.

PMID- 11333807
TI  - [Changes in chest wall and lung compliance during laparoscopic cholecystectomy].
AB  - INTRODUCTION: The performance of laparoscopic cholecystectomy leads to
      hemodynamic and gasometric changes as well as to mechanical changes in
      respiration. The last phenomenon has been less studied in spite of its impact on
      the patient during surgery. OBJECTIVE: To study changes in chest wall compliance
      (Ccw) and lung compliance (CL) during laparoscopic cholecystectomy. Material and
      methods. Nine patients scheduled for laparoscopic cholecystectomy were enrolled.
      Tidal volume, plateau pressure (Pt) and esophageal (Pes) were measured and the
      data were used to calculate respiratory system compliance (Crs), Ccw and CL.
      Measurements were taken at three moments: T1, with the patients in supine
      decubitus position; T2, in anti-Trendelenburg position with pneumoperitoneum; T3,
      after withdrawal of pneumoperitoneum with the patient in supine decubitus
      position. RESULTS: Pt was seen to increase 57%, with a 100% increase in Pes when
      the patient was placed in anti-Trendelenburg position and pneumoperitoneum was
      established. Crs changed 44%, with a greater increase taking place in Ccw (52%)
      than in CL (32%). Baseline values for both pressure and compliance were recovered
      by T3. CONCLUSIONS: Reduced respiratory compliance occurs during laparoscopic
      cholecystectomy mainly at the chest wall, with much less reduction taking place
      in the lung. Thus, intrathoracic pressure increases will be greater than
      transpulmonary pressure increases.

PMID- 11333808
TI  - [Ventricular assist support of the failing heart after surgery with
      extracorporeal circulation].
AB  - OBJECTIVE: To communicate our experience implanting ventricular assist devices;
      we report the incidence of refractory heart failure after extracorporeal
      circulatory support and discuss clinical course after support. PATIENTS AND
      METHOD: Retrospective study of 14 cases of ventricular assistance required when
      refractory heart failure developed after extracorporeal circulation. The patients
      were 10 males and 4 females aged between 12 and 70 years. Four underwent coronary
      revascularization, 2 required valve replacement, and 8 received heart
      transplants. Two left, 2 right and 6 bilateral ventricular assist devices were
      implanted. RESULTS: The incidence of refractory heart failure after
      extracorporeal mechanical circulation requiring ventricular assist devices among
      our patients was 0.48%, with left ventricular failure occurring in 21.42%, right
      ventricular failure in 42.85% and biventricular failure in 35.71%. The main
      complications were infection, renal insufficiency, coagulation disorder,
      hemorrhage with repeated surgery. One patient received a second transplant. The
      device was successfully withdrawn from 35.7% of the patients. Survival upon
      discharge was 7.1%. CONCLUSION: Refractory heart failure after extracorporeal
      circulation is a life-threatening event requiring rapid response and resolution.
      The decision to implant a ventricular assist device is a difficult one, requiring
      immediate assessment of the causes of heart failure, its reversibility and the
      possibility of performing a heart transplant. The study of large series of
      patients experiencing this event and implanted with ventricular assist devices
      would facilitate decision making.

PMID- 11333809
TI  - [General principles for the clinical organization and management of a surgical
      unit].
AB  - Because health-care costs and demand for services are both rising, appropriate
      management of resources is yet another essential consideration in efficient
      clinical practice. Surgical units, with their special features, are a particular
      focus of attention. Although it is possible to study the circumstances of each
      hospital individually, in fact surgical units often share the same management
      concerns. Currently, surgical units are often reorganized and provided with an
      Operating Room Committee, a Medical director or coordinator and operational
      protocols, such that the unit is considered a system rather than a sum of its
      individual parts. Work is goal-oriented, with starting and ending points,
      flexibility in use of surgical theaters, reserve capacity for unscheduled
      surgery, low cancellation rates and good output; the use of time indicators is
      considered essential. Other factors to bear in mind when managing a surgical unit
      are the universalization of information, which should be accurate and up to date,
      the involvement of teams such as that of anesthesia and recovery, scheduling that
      is realistic and tight, the appropriate design and use of circuits, and the use
      of techniques for continuous improvement and problem solving. Some programs, such
      as that of major outpatient surgery, orthopedic surgery and others may have
      special needs.

PMID- 11333810
TI  - [Pulmonary atelectasis during anesthesia in a boy with upper respiratory tract
      infection].
AB  - A 6-year-old boy was scheduled for adenoidectomy and bilateral myringotomy. The
      main features of his case history were chronic otitis media, bronchial asthma and
      signs and symptoms of upper respiratory tract infection (persistent runny nose
      and cough, occasionally with fever). Immediately after tracheal intubation we
      observed that the right side of the chest failed to rise with inspiration;
      breathing sounds were absent on the right and hypoxemia developed. A chest film
      taken in the operating room revealed upper right lobe atelectasis. Surgery was
      postponed and tracheobronchial lavage was performed with fiberoptic bronchoscopy
      and aspiration of mucous plugs. Upper airway infections are a common problem in
      children and increase the risk of respiratory complications during anesthesia.
      Patients with upper respiratory tract symptoms present a dilemma, and consensus
      about how to deal with such situations is lacking. We review the literature,
      discuss the anesthetic implications of upper airway infections, and suggest a two
      phase approach for cases such as we report: first myringotomy using general
      anesthesia and a face mask, and second, once the upper airway infection has
      resolved, adenoidectomy with general anesthesia and tracheal intubation.

PMID- 11333811
TI  - [Cerebrospinal fluid drainage and deep systemic hypothermia with total absence of
      circulation for spinal cord protection during surgery on the thoracic aorta].
AB  - A 53-yearold man with a dissecting aneurysm of Stanford's type-B or Crawford's
      type I measuring 8.5 cm in diameter underwent replacement of the distal
      descending aorta and the thoracic aorta using techniques for spinal cord
      protection involving deep hypothermia at 17 degrees C and lasting 38 minutes with
      total absence of circulation. A subarachnoid catheter was inserted at the lumbar
      level to monitor spinal fluid pressure as well as to provide drainage if pressure
      exceeded 10 mm Hg. During surgery 60 ml was drained, followed by 95 ml after
      surgery on the same day and 325, 262 and 169 ml on the following three days. No
      signs of neurological deficit were observed during the postoperative period.
      Clinical course was good until hypovolemic shock developed 27 days after the
      operation due to upper digestive tract bleeding caused by two duodenal ulcers
      that perforated the gastroduodenal artery. Emergency antrectomy and vagotomy were
      performed. The patient died from multiple organ failure. Spinal cord injury
      continues to be one of the most feared complications after excision of thoracic
      and thoracoabdominal aorta aneurysm. Currently, various ways of protecting the
      spinal cord are practiced, including drainage of cerebrospinal fluid, partial
      bypass of the femoral artery, intercostal artery reimplantation, drug therapy and
      local spinal and/or systemic hypothermia. These methods, together with shorter
      clamping time have achieved a reduction in the incidence of spinal cord injuries.

PMID- 11333812
TI  - [Subarachnoid anesthesia in a case of mitochondrial myopathy].

PMID- 11333813
TI  - [Anesthesia for major scoliosis in Prader-Willi syndrome].

PMID- 11333814
TI  - [Comment on the article "Use of EMLA cream and ropivacaine
      indacryocystorhinostomy with locoregional anesthesia and sedation"].

PMID- 11333815
TI  - [Neurological diagnosis of death].

PMID- 11333816
TI  - [Prognostic value of cardiac perfusion scintigraphy associated with the
      dobutamine test in acute coronary syndromes].
AB  - OBJECTIVES: This study aimed to establish the value of myocardial ischemia
      induced by the dobutamine infusion test associated to 99m technetium isonitrile
      single photon emission computed tomography in patients with unstable angina or
      non Q-wave infarction during the first days in the Coronary Care Unit. METHODS:
      Fifty three patients with unstable coronary syndromes and common medical
      treatment were studied with a moderate-dose dobutamine test (5 to 20
      microgram/Kg/min) using a 99mTc-MIBI SPECT. The results were correlated with the
      incidence of recurrent angina, infarction, death or revascularization. RESULTS:
      The dobutamine test induced a reversible perfusion defect in 36 patients (68%)
      and angina in 12 of them (12/36, 33%). However, the patients who had a positive
      test had a similar incidence of events as those with a negative test (58% vs
      59%). Thus, while the sensitivity of the dobutamine test to identify patients at
      risk was relatively high (68%), its specificity (32%) and its negative predictive
      value (41%) were low. The patients with dobutamine-induced angina, however, had a
      higher scintigraphy score (3.0 +/- 1,7 vs 1.6 +/- 1.8, p < 0.02) and a higher
      incidence of recurrent angina (8/12, 67% vs 13/41, 31%, p < 0.04) than those
      without, at a comparable double product. CONCLUSIONS: In conventionally treated
      patients with unstable coronary syndromes, the specificity of the inducible
      scintigraphic ischemia with moderate dose of dobutamine performed during the
      first days is too low to be used as a marker for in-hospital events. However,
      inducible angina with dobutamine suggests an extensive jeopardized area and/or a
      particularly reduced ischemic threshold.

PMID- 11333817
TI  - [Utility of SPECT with 99m Tc-tetrofosmin and stimulus with dipyridamole in
      patients with permanent ventricular pacemakers].
AB  - BACKGROUND AND OBJECTIVE: Patients with permanent ventricular pacemakers (PP) are
      a difficult subgroup to assess in the study of coronary artery disease. The
      objective of this study was to evaluate the diagnostic value of the myocardial
      perfusion scintigraphy with 99mTC-Tetrofosmin (Tc-Tf) and stimulus with
      dipyridamole in patients with PP and suspected coronary artery disease. PATIENTS
      AND METHODS: Fourteen patients with suspected coronary artery disease and without
      structural cardiopathy, who underwent Tc-Tf and cardiac catheterization, were
      studied retrospectively. Sensitivity, specificity, predictive values and Kappa
      index were calculated for the diagnosis of coronary artery disease, multivessel
      disease, and for each one of the coronary arteries (left anterior descending,
      right coronary, and circumflex). In addition, the correlation between the number
      of territories with perfusion defects and the number of diseased vessels was
      studied. RESULTS: In regards to the diagnosis of coronary artery disease,
      sensitivity, specificity, positive predictive value, negative predictive value
      and the Kappa index were 100%, 50%, 83%, 100% and 0.55, respectively. For multi
      vessel disease, these values were 83%, 64%, 64%, 83% and 0.43 respectively. The
      correlation coefficient between the number of territories with perfusion defects
      and the number of diseased vessels was 0.61 (p = 0.02). In the diagnosis of
      anterior descending disease, sensitivity and specificity were 83% and 88%
      respectively. For the right coronary artery, these values were 100% and 44% and
      for the circumflex artery 38% and 83%, respectively. CONCLUSION: In patients with
      PP and suspected coronary artery disease, myocardial perfusion scintigraphy with
      Tc-Tf and stimulus with dipyridamole is of great value in the diagnosis of
      coronary artery disease and in the assessment of its extension.

PMID- 11333818
TI  - [Tomographic studies of myocardial perfusion normality with 99m Tc-Tetrofosmin.
      Spanish multicenter study].
AB  - As a first phase in a nationwide multicenter study to obtain myocardial perfusion
      normality patterns, this work presents the study design and quality control
      methodology used to guarantee that the gammacameras fulfilled some minimum
      quality requirements. The following aspects were considered in the study design
      in order to guarantee the homogeneity and interchangeability of the results:
      creation and structure of the work group, data interchange system, data selection
      and acquisition, centralized archiving and processing, assessment system, study
      acceptance criteria and distribution of the results. To carry out the
      instrumental quality control, three phantom studies were established, one to
      control the rotation center, another to verify tomographic uniformity and a third
      to simulate the shape and orientation of the left ventricle. The three phantoms
      circulated through all of the 18 participating centers in this project, which
      corresponded to 19 gammacameras. Very strict guidelines had to be followed in the
      acquisition and processing of these phantom studies. If any camera and/or center
      did not fulfill the criteria established, it was advised of the problem detected
      in order to correct it. Once the defect was repaired, all the phantoms were sent
      again for verification. Uniformity of the rotation center was quantified by means
      of the eccentricity of a 360 degrees orbit, admitting up to a maximum of 10%.
      Tomographic uniformity was visually assessed, taking in account the number of
      slices with rings and their contrast and finally no artifacts could be present in
      the reconstructed study of the ventricle. The center of rotation was within
      limits in all the cameras except one case while the tomographic uniformity was
      incorrect in 6 cases. All the departments, except one, corrected the defects
      detected, and passed the acceptance test. The results made it possible to
      guarantee adequate homogeneity and instrumental quality in this multicenter
      study.

PMID- 11333820
TI  - [Welcome the multicenter studies].

PMID- 11333819
TI  - [Tomographic studies of myocardial perfusion normality with 99m Tc-Tetrofosmin.
      Spanish multicenter study].
AB  - This objective of this study was to obtain a pool of Myocardial Perfusion SPECTs
      with a 99mTetrofosmin stress/rest one day protocol in normal volunteers having a
      less than or equal to 5% likelihood of coronary artery disease that represents
      normalcy in the Spanish population. A total of 169 volunteers from 15 hospitals
      were studied. The volunteers were divided into 5 groups: Groups 1, 2 or 3
      corresponding to men < 30 years (n = 33), men between 30 and 50 years (n = 32),
      or men > 50 years (n = 31); Groups 4 or 5: premenopausal (n = 38) or
      postmenopausal women (n = 35). A clinical history, physical examination, clinical
      laboratory parameters, echocardiography and a symptom limited exercise stress
      test were performed in all of them and had to be normal. The mean likelihood of
      coronary artery disease was 1.15 +/- 1.07%.Twenty-four segments were analyzed in
      each study and were classified into 5 grades of uptake (1 = normal, 2, 3, 4 =
      mild, moderate or severe defect and 5 = no uptake). Defects were then analyzed
      according to sex and location. Considering the stress and rest studies separately
      (8,112 segments), only 19 moderate and 75 mild defects were found, these
      corresponding to 16 volunteers, with more inferior defects in men and anterior
      defects in women. These data validate the normalcy of our population. A pool of
      Myocardial Perfusion SPECTs with a 99mTetrofosmin stress/rest one day protocol in
      normal volunteers that represents Spanish normal values was obtained.

PMID- 11333821
TI  - [Association of thyroid hemiagenesis and Graves disease].
AB  - Thyroid hemiagenesis is a very infrequent abnormality. We present a case of
      Graves disease associated to a congenital hemiagenesis of the thyroid gland. The
      thyroid scintigraphy, ultrasonography and laboratory analysis (that showed the
      existence of thyroid hyperfunction and the present of thyroid stimulating
      antibodies) were decisive in the diagnosis.

PMID- 11333822
TI  - Positive imaging of an inflammatory process at an arteriovenous access site with
      111 Indium-labeled platelets.
AB  - Complications associated with the vascular access for hemodialysis represent one
      of the most important causes of morbidity among patients with renal replacement
      therapy. Early detection of arteriovenous fistula (AVF) dysfunction is of great
      interest. We present the case of a 70 year old woman who underwent 111In-oxine
      labeled-platelet scintigraphy to evaluate thrombogenicity at 3 weeks and 3 months
      after surgery of a new AVF. In the first post-operative scintigraphy 4 hours
      after reinjection of autologous 111In-labeled platelets, enhanced focal activity
      was visible in the AVF projection which could not be detected after 24 hours.
      Since early platelet accumulation may reflect hyperemia in inflammation, this
      diagnosis was verified by anti-granulocyte antibody scintigraphy. The platelet
      scintigraphy performed 3 months later was negative, with persistence of
      sufficient AVF function. These data show an intense early accumulation of 111In
      oxine-labeled-platelets in unspecific inflammation of an AVF.

PMID- 11333823
TI  - [Role of nuclear medicine in the diagnosis of brain death].

PMID- 11333824
TI  - [Detection of relapse in ovarian cancer by PET-FDG].

PMID- 11333825
TI  - [153Sm-EDTMP in a patient suffering from colon cancer with bone metastasis].

PMID- 11333826
TI  - [The bone scintigraphy in the diagnosis and assessment of sports related
      injuries].

PMID- 11333827
TI  - [Human gonadotrophic hormone (HCG) in benign breast cyst fluid. Association
      between type I and type II biological activities].

PMID- 11333828
TI  - [Second International Sentinel Node Congress].

PMID- 11333830
TI  - Quantitative trait loci (QTLs) mapping for growth traits in the mouse: a review.
AB  - The attainment of a specific mature body size is one of the most fundamental
      differences among species of mammals. Moreover, body size seems to be the central
      factor underlying differences in traits such as growth rate, energy metabolism
      and body composition. An important proportion of this variability is of genetic
      origin. The goal of the genetic analysis of animal growth is to understand its
      "genetic architecture", that is the number and position of loci affecting the
      trait, the magnitude of their effects, allele frequencies and types of gene
      action. In this review, the different strategies developed to identify and
      characterize genes involved in the regulation of growth in the mouse are
      described, with emphasis on the methods developed to map loci contributing to the
      regulation of quantitative traits (QTLs).

PMID- 11333831
TI  - Bayes factors for detection of quantitative trait loci.
AB  - A fundamental issue in quantitative trait locus (QTL) mapping is to determine the
      plausibility of the presence of a QTL at a given genome location. Bayesian
      analysis offers an attractive way of testing alternative models (here, QTL vs. no
      QTL) via the Bayes factor. There have been several numerical approaches to
      computing the Bayes factor, mostly based on Markov Chain Monte Carlo (MCMC), but
      these strategies are subject to numerical or stability problems. We propose a
      simple and stable approach to calculating the Bayes factor between nested models.
      The procedure is based on a reparameterization of a variance component model in
      terms of intra-class correlation. The Bayes factor can then be easily calculated
      from the output of a MCMC scheme by averaging conditional densities at the null
      intra-class correlation. We studied the performance of the method using
      simulation. We applied this approach to QTL analysis in an outbred population. We
      also compared it with the Likelihood Ratio Test and we analyzed its stability.
      Simulation results were very similar to the simulated parameters. The posterior
      probability of the QTL model increases as the QTL effect does. The location of
      the QTL was also correctly obtained. The use of meta-analysis is suggested from
      the properties of the Bayes factor.

PMID- 11333832
TI  - A rapid method for computing the inverse of the gametic covariance matrix between
      relatives for a marked quantitative trait locus.
AB  - The inverse of the gametic covariance matrix between relatives, G(-1), for a
      marked quantitative trait locus (QTL) is required in best linear unbiased
      prediction (BLUP) of breeding values if marker data are available on a QTL. A
      rapid method for computing the inverse of a gametic relationship matrix for a
      marked QTL without building G itself is presented. The algorithm is particularly
      useful due to the approach taken in computing inbreeding coefficients by having
      to compute only few elements of G. Numerical techniques for determining, storing,
      and computing the required elements of G and the nonzero elements of the inverse
      are discussed. We show that the subset of G required for computing the inbreeding
      coefficients and hence the inverse is a tiny proportion of the whole matrix and
      can be easily stored in computer memory using sparse matrix storage techniques.
      We also introduce an algorithm to determine the maximum set of nonzero elements
      that can be found in G(-1) and a strategy to efficiently store and access them.
      Finally, we demonstrate that the inverse can be efficiently built using the
      present techniques for very large and inbred populations.

PMID- 11333833
TI  - Genetic parameters of eventing horse competition in France.
AB  - Genetic parameters of eventing horse competitions were estimated. About 13 000
      horses, 30 000 annual results during 17 years and 110 000 starts in eventing
      competitions during 8 years were recorded. The measures of performance were
      logarithmic transformations of annual earnings, annual earnings per start, and
      annual earnings per place, and underlying variables responsible for ranks in each
      competition. Heritabilities were low (0.11 / 0.17 for annual results, 0.07 for
      ranks). Genetic correlations between criteria were high (greater than 0.90)
      except between ranks and earnings per place (0.58) or per start (0.67). Genetic
      correlations between ages (from 5 to 10 years old) were also high (more than
      0.85) and allow selection on early performances. The genetic correlation between
      the results in different levels of competition (high/international and
      low/amateur) was near 1. Genetic correlations of eventing with other disciplines,
      which included partial aptitude needed for eventing, were very low for
      steeplechase races (0.18) and moderate with sport: jumping (0.45), dressage
      (0.58). The results suggest that selection on jumping performance will lead to
      some positive correlated response for eventing performance, but much more
      response could be obtained if a specific breeding objective and selection
      criteria were developed for eventing.

PMID- 11333834
TI  - Development and assignment of bovine-specific PCR systems for the Texas
      nomenclature marker genes and isolation of homologous BAC probes.
AB  - In 1996, Popescu et al. published the Texas standard nomenclature of the bovine
      karyotype in which 31 marker genes, already mapped in man, were chosen to permit
      unambiguous identification and numbering of each bovine chromosome. However,
      specific PCR systems were not available for each marker gene thus preventing the
      assignment of part of these markers by somatic cell hybrid analysis. In addition,
      some difficulties remained with the nomenclature of BTA25, BTA27 and BTA29. In
      this work, specific PCR systems were developed for each of the marker genes
      except VIL1 (see results), from either existing bovine or human sequences, and a
      bovine BAC library was screened to obtain the corresponding BAC clones. These PCR
      systems were used successfully to confirm the assignment of each marker gene
      (except for LDHA, see results) by analysis on the INRA hamster-bovine somatic
      cell hybrid panel. The difficulties observed for LDHA and VIL1 are probably due
      to the fact that these genes belong to large gene families and therefore suggest
      that they may not be the most appropriate markers for a standardisation effort.
      This panel of BACs is available to the scientific community and has served as a
      basis for the establishment of a revised standard nomenclature of bovine
      chromosomes.

PMID- 11333835
TI  - "Appropriate technology" for vitamin A field research.

PMID- 11333836
TI  - Body composition and anorexia nervosa: does physiology explain psychology?

PMID- 11333837
TI  - Nutritional skin care: health effects of micronutrients and fatty acids.
AB  - Human skin is continuously exposed to internal and external influences that may
      alter its condition and functioning. As a consequence, the skin may undergo
      alterations leading to photoaging, inflammation, immune dysfunction, imbalanced
      epidermal homeostasis, or other skin disorders. Modern nutritional science is
      developing new insights into the relation between food intake and health, and
      effects of food ingredients may prove to be biologically relevant for optimal
      skin condition. The objective of this review was to evaluate the present
      knowledge about the interrelation of nutrients and skin, particularly the
      photoprotective effects of nutrients, the influences of nutrients on cutaneous
      immune responses, and therapeutic actions of nutrients in skin disorders. The
      nutrients of focus were vitamins, carotenoids, and polyunsaturated fatty acids.
      Supplementation with these nutrients was shown to provide protection against
      ultraviolet light, although the sun-protection factor was relatively small
      compared with that of topical sunscreens. An increase in delayed-type
      hypersensitivity skin responses after supplementation with nutrients has proven
      beneficial, especially in elderly people, and may boost cell-mediated immunity.
      Dietary consumption of certain plants or fish oil is known to modulate the
      balance of lipid inflammatory mediators and, therefore, is valuable in the
      treatment of inflammatory skin disorders. It was concluded that nutritional
      factors exert promising actions on the skin, but information on the effects of
      low-to-moderate doses of nutrients consumed long term by healthy individuals is
      obviously lacking, as are data on direct effects on basal skin properties,
      including hydration, sebum production, and elasticity.

PMID- 11333838
TI  - Changes in regional fat redistribution and the effects of estrogen during
      spontaneous weight gain in women with anorexia nervosa.
AB  - BACKGROUND: Anorexia nervosa is a disease of severe acquired undernutrition with
      a high and increasing prevalence among young women in the United States.
      OBJECTIVE: The objective was to investigate the effects of spontaneous outpatient
      weight recovery and estrogen administration on fat distribution in patients with
      anorexia nervosa. DESIGN: Twenty-seven amenorrheic women aged 26.6 +/- 1.2 y with
      anorexia nervosa were identified through an outpatient study of bone loss and
      were randomly assigned to receive or not receive estrogen without any dietary
      intervention other than calcium and multivitamin supplements. Body composition
      was measured at baseline and at 6 and 9 mo and was compared with cross-sectional
      values obtained in 20 healthy, eumenorrheic, age-matched (25.4 +/- 0.5 y) control
      subjects. RESULTS: Twenty of the 27 patients with anorexia aged 27.0 +/- 1.3 y
      spontaneously gained weight (4.1 +/- 0.9 kg); body mass index (in kg/m(2))
      increased from 16.1 +/- 0.3 to 17.5 +/- 0.4. Fat mass and lean mass accounted for
      68% and 32% of the gain in total body mass, respectively. With spontaneous weight
      gain, there was a significant increase in the percentage of trunk fat from 32.4
      +/- 1.3% at baseline to 36.5 +/- 1.0% at 9 mo (P = 0.03), which correlated with
      urinary free cortisol (r = 0.66, P = 0.003). Estrogen treatment was not
      protective against the gain in trunk fat with spontaneous weight gain.
      CONCLUSIONS: In women with anorexia nervosa, spontaneous weight gain is
      associated with a significant increase in trunk adiposity, and estrogen
      administration may not protect against the accumulation of central fat with
      weight gain.

PMID- 11333839
TI  - Dietary cholesterol is secreted in intestinally derived chylomicrons during
      several subsequent postprandial phases in healthy humans.
AB  - BACKGROUND: The process of intestinal absorption and chylomicron resecretion of
      dietary cholesterol in humans is poorly understood. OBJECTIVE: The present study
      aimed to test the hypothesis that dietary cholesterol ingested during a given
      meal is resecreted into chylomicrons (and plasma) during several subsequent
      postprandial periods. DESIGN: Seven healthy subjects ingested 3 comparable mixed
      test meals (at 0, 8, and 24 h) containing a given amount of fat (49 g) and
      cholesterol (157 mg); blood samples were taken 3 and 6 h after each test meal and
      48 and 72 h after the beginning of the experiment. Heptadeuterated dietary
      cholesterol was present in the first test meal only, enabling its specific
      determination with use of gas chromatography-mass spectrometry. Chylomicrons,
      LDL, and HDL were isolated and lipids were quantified. RESULTS: In apolipoprotein
      B-48-containing chylomicrons, deuterated cholesterol concentrations were moderate
      after the first meal (1.3 x 10(-4) mmol/L), reached a maximum after the second
      meal (2.4 x 10(-4) mmol/L), and were still elevated after the third meal (1.7 x
      10(-4) mmol/L). In plasma, LDL and HDL cholesterol enrichment in deuterated
      cholesterol was lower than in chylomicrons and plateaued after 24--48 h.
      Estimates of newly secreted exogenous deuterated cholesterol in chylomicrons
      indicate that 30.7%, 55.2%, and 14.1% of the total was secreted after the first,
      second, and third meals, respectively. CONCLUSION: Ingested dietary cholesterol
      is secreted by the small intestine in chylomicrons into the circulation during >
      or =3 subsequent postprandial periods in healthy humans. This likely results from
      a complex multistep intestinal processing of cholesterol with dietary fat as a
      driving force.

PMID- 11333840
TI  - Effects of isoenergetic high-carbohydrate compared with high-fat diets on human
      cholesterol synthesis and expression of key regulatory genes of cholesterol
      metabolism.
AB  - BACKGROUND: High-carbohydrate diets improve plasma cholesterol concentrations but
      increase triacylglycerol concentrations; the latter effect increases the risk of
      cardiovascular disease (CVD). Triacylglycerol concentrations increase only during
      very-high-carbohydrate diets consisting mainly of simple sugars. OBJECTIVE: We
      compared the CVD risk profile, cholesterol metabolism, and glucose tolerance of 7
      healthy subjects during 2 isoenergetic diets: a high-fat, low-carbohydrate diet
      (HF diet) and a moderately high-carbohydrate, low-fat diet (HC diet). DESIGN: In
      a randomized crossover study, we measured the effects of the HF diet [40%
      carbohydrate and 45% fat (15% saturated, 15% monounsaturated, and 15%
      polyunsaturated)] and HC diet [55% carbohydrate (mainly complex) and 30% fat (10%
      saturated, 10% monounsaturated, and 10% polyunsaturated)] (3 wk each) on plasma
      lipid concentrations, oral glucose tolerance, cholesterol synthesis rate, and the
      messenger RNA (mRNA) concentrations of beta-hydroxy-beta-methylglutaryl coenzyme
      A (HMG-CoA) reductase, the LDL receptor, and the LDL-receptor-related protein
      (LRP). RESULTS: Compared with the HF diet, the HC diet lowered total, LDL, and
      HDL cholesterol (P < 0.05 for all) without modifying the ratio of LDL to HDL
      cholesterol; triacylglycerol concentrations were unchanged. Lower cholesterol
      concentrations occurred despite a higher cholesterol synthesis rate (P < 0.05)
      and higher HMG-CoA reductase mRNA concentrations (P < 0.05). LDL receptor mRNA
      concentrations were unchanged, LRP mRNA concentrations were lower (P < 0.01), and
      oral glucose tolerance was better (P < 0.05) with the HC diet. CONCLUSION: The
      beneficial effects of the HC diet on glucose tolerance and plasma cholesterol
      concentrations without increases in triacylglycerol show that this diet had
      favorable effects on both insulin sensitivity and the plasma lipid profile.

PMID- 11333841
TI  - Dietary cholesterol from eggs increases the ratio of total cholesterol to high
      density lipoprotein cholesterol in humans: a meta-analysis.
AB  - BACKGROUND: Several epidemiologic studies found no effect of egg consumption on
      the risk of coronary heart disease. It is possible that the adverse effect of
      eggs on LDL-cholesterol is offset by their favorable effect on HDL cholesterol.
      OBJECTIVE: The objective was to review the effect of dietary cholesterol on the
      ratio of total to HDL cholesterol. DESIGN: Studies were identified by MEDLINE and
      Biological Abstracts searches (from 1974 to June 1999) and by reviewing reference
      lists. In addition, we included data from a more recently published study.
      Studies were included if they had a crossover or parallel design with a control
      group, if the experimental diets differed only in the amount of dietary
      cholesterol or number of eggs and were fed for > or =14 d, and if HDL-cholesterol
      concentrations were reported. Of the 222 studies identified, 17 studies involving
      556 subjects met these criteria. RESULTS: The addition of 100 mg dietary
      cholesterol/d increased the ratio of total to HDL cholesterol by 0.020 units (95%
      CI: 0.010, 0.030), total cholesterol concentrations by 0.056 mmol/L (2.2 mg/dL)
      (95% CI: 0.046, 0.065 mmol/L; 1.8, 2.5 mg/dL), and HDL-cholesterol concentrations
      by 0.008 mmol/L (0.3 mg/dL) (95% CI: 0.005, 0.010 mmol/L; 0.2, 0.4 mg/dL).
      CONCLUSIONS: Dietary cholesterol raises the ratio of total to HDL cholesterol
      and, therefore, adversely affects the cholesterol profile. The advice to limit
      cholesterol intake by reducing consumption of eggs and other cholesterol-rich
      foods may therefore still be valid.

PMID- 11333842
TI  - Mechanism for the increase in plasma triacylglycerol concentrations after
      consumption of short-term, high-carbohydrate diets.
AB  - BACKGROUND: High-carbohydrate (HC) diets are recommended for lowering the risk of
      coronary heart disease because they decrease plasma LDL-cholesterol
      concentrations. However, an unfavorable effect of HC diets is an increase in
      plasma triacylglycerol concentrations. The underlying mechanisms of this effect
      are still unclear. OBJECTIVE: We examined the effect of diet composition on VLDL
      triacylglycerol metabolism using in vivo isotopically labeled VLDL
      triacylglycerol tracers. DESIGN: Six healthy subjects were studied on 2
      occasions: after 2 wk of an HC diet (75% carbohydrates, 10% fat, and 15% protein)
      and after 2 wk of an isoenergetic high-fat (HF) diet (30% carbohydrates, 55% fat,
      and 15% protein). RESULTS: The plasma VLDL-triacylglycerol concentration was
      higher after the HC diet than after the HF diet (690 +/- 186 compared with 287 +/
      104 micromol/L; P < 0.05) because of higher rates of VLDL-triacylglycerol
      production (0.76 +/- 0.12 compared with 0.45 +/- 0.15 micromol x kg(-1) x min(
      1); P < 0.05) rather than diminished VLDL-triacylglycerol clearance (1.5 +/- 0.5
      compared with 1.7 +/- 0.5 mL x kg(-1) x min(-1) after the HC diet than after the
      HF diet, respectively). The increase in VLDL-triacylglycerol production was
      probably mediated by a decrease in hepatic fatty acid oxidation after the HC diet
      (0.13 +/- 0.02 compared with 0.69 +/- 0.24 micromol x kg(-1) x min(-1); P <
      0.05), which presumably increased hepatic fatty acid availability for
      triacylglycerol synthesis. CONCLUSIONS: The increase in fasting plasma
      triacylglycerol concentrations in response to short-term HC diets is due to
      accelerated VLDL-triacylglycerol secretion. Increased hepatic fatty acid
      availability, resulting from reduced hepatic fatty acid oxidation, is most likely
      responsible for the observed increase in VLDL-triacylglycerol secretion.

PMID- 11333844
TI  - Amino acid kinetics in patients with sepsis.
AB  - BACKGROUND: In patients with sepsis and systemic inflammatory response syndrome,
      amino acid extraction by the liver is enhanced, resulting in decreased plasma
      amino acid concentrations. Systematic investigations of the elimination of
      intravenously infused amino acids have not been performed. OBJECTIVE: The
      objective of this study was to compare the elimination of 17 amino acids in
      patients with sepsis and in healthy control subjects. DESIGN: Elimination of
      amino acids was evaluated in 9 patients with sepsis and in 8 healthy control
      subjects by using a combined loading and maintenance infusion of 375 mg amino
      acids/kg body wt for 60 min. Pharmacokinetic variables were analyzed from plasma
      curves. RESULTS: With the exception of lysine, methionine, glutamate, ornithine,
      phenylalanine, and tyrosine, plasma concentrations of amino acids were lower in
      the patients with sepsis than in the control subjects; phenylalanine was the only
      amino acid whose plasma concentration increased (P < 0.001). In patients with
      sepsis, whole-body clearance (Cl(tot)) of total amino acids was 74% higher than
      in control subjects (x +/- SEM: 13,161 +/- 1659 and 7566 +/- 91 mL/min,
      respectively; P < 0.01), the Cl(tot) of essential amino acids was 64% higher (P <
      0.02), that of nonessential amino acids was 82% higher (P < 0.01), and that of
      both branched-chain amino acids and glucogenic amino acids was 97% higher (P <
      0.001). With the exception of phenylalanine, ornithine, proline, and glutamate,
      the Cl(tot) of all amino acids was elevated. The Cl(tot) of phenylalanine and
      ornithine decreased slightly (NS). CONCLUSIONS: In patients with sepsis, plasma
      concentrations of most amino acids are greatly decreased and the elimination of
      amino acids from the intravascular space during intravenous infusion is greatly
      enhanced.

PMID- 11333843
TI  - Lysine requirements of healthy adult Indian subjects, measured by an indicator
      amino acid balance technique.
AB  - BACKGROUND: In an earlier study, using a modification of the indicator amino acid
      oxidation approach, we concluded that the 1985 FAO/WHO/UNU-proposed lysine
      requirement of 12 mg x kg(-1) x d(-1) is likely inadequate to maintain body amino
      acid homeostasis in apparently healthy south Asian subjects and that our proposed
      requirement of 30 mg x kg(-1) x d(-1) is more appropriate. OBJECTIVE: We assessed
      the lysine requirement in a similar population by using 4 test lysine intakes
      (12, 20, 28, and 36 mg x kg(-1) x d(-1)) with an indicator amino acid balance
      approach. DESIGN: Sixteen healthy male Indians were studied during each of 2
      randomly assigned 8-d L-amino acid diets that supplied either 12 and 28 or 20 and
      36 mg lysine. At 1800 on day 8, a 24-h intravenous [(13)C]leucine tracer-infusion
      protocol was conducted to assess leucine oxidation and daily leucine balance at
      each lysine intake. RESULTS: Mean 24-h leucine oxidation rates decreased
      significantly (P = 0.005) across different lysine intakes and were 104.1, 97.8,
      87.3, and 87.3 mg x kg(-1) x d(-1) at intakes of 12, 20, 28, and 36 mg x kg(-1) x
      d(-1), respectively; mean 24-h leucine balances were 3.3, 9.1, 19.7, and 20.7 mg
      x kg(-1) x d(-1), respectively (P = 0.015, mixed-model analysis of variance).
      Oxidation and balances differed significantly between the lower and higher lysine
      intakes but were not significantly different between the 12- and 20-mg and 28-
      and 36-mg test intakes. Two-phase regression analysis indicated a mean breakpoint
      at 29 mg lysine x kg(-1) x d(-1) in the relation between lysine intake and
      leucine oxidation or balance. CONCLUSION: We propose a mean lysine requirement of
      30 mg x kg(-1) x d(-1) for healthy Indian adults, which is the same amount we
      proposed previously for Western populations.

PMID- 11333845
TI  - Extent of thermal processing of infant formula affects copper status in infant
      rhesus monkeys.
AB  - BACKGROUND: Infant rhesus monkeys are excellent models in which to study the
      effect of infant formulas on trace element absorption and status. Infants fed
      powdered formula from birth exhibit normal growth and have blood variables
      similar to those of breast-fed infants. OBJECTIVES: The objectives were to
      evaluate the effects of feeding ready-to-feed (RTF) formulas exposed to different
      heat treatments to infant monkeys, and, for one of these formulas, to compare the
      effect of fortification with 2 iron concentrations. DESIGN: From birth to age 5
      mo, infant monkeys (n = 6/group) were fed one of the following formulas
      exclusively: 1) 12 mg Fe/L processed in cans (RTF-12), 2) formula in glass
      bottles with 12 mg Fe/L and manufactured by an ultrahigh-temperature (UHT)
      process (UHT-12), or 3) formula manufactured by a standard thermal process (STP),
      containing either 8 (STP-8) or 12 (STP-12) mg Fe/L. All formulas had similar
      copper concentrations (0.6 mg Cu/L). Anthropometric measures and venous blood
      samples were taken monthly. RESULTS: Weight and length gain did not differ among
      groups; however, the STP-12 group weighed less than the UHT-12 group at ages 2,
      4, and 5 mo. Hemoglobin values were significantly lower in the RTF-12 group than
      in all other groups at ages 4 and 5 mo and serum ferritin was lower in the RTF-12
      group than in the STP-12 group at age 5 mo. Copper status was lower in STP-12
      infants than in STP-8 infants. There was a progressive and significant decline in
      plasma copper, ceruloplasmin, and Cu/Zn superoxide dismutase activity in infants
      fed canned formula (RTF-12). Furthermore, coat color changed from normal brown to
      silver. These outcomes suggest that the canned formula induced copper deficiency
      in infant monkeys. CONCLUSIONS: Excessive heat treatment of formula can have a
      pronounced negative effect on copper status. High iron concentrations did not
      improve iron status but may adversely affect copper status.

PMID- 11333846
TI  - Anthocyanins are absorbed in glycated forms in elderly women: a pharmacokinetic
      study.
AB  - BACKGROUND: Anthocyanins are potent antioxidants that are widely distributed in
      fruit, vegetables, and red wines. Anthocyanin products are also prescribed as
      medicines in many countries for treating various diseases. However, the
      pharmacokinetics of dietary anthocyanins are not known in humans because these
      glycosides were long considered nonabsorbable. OBJECTIVE: The objective of this
      study was to determine whether anthocyanins can be absorbed as glycosides and to
      evaluate their pharmacokinetics in humans. DESIGN: Four healthy elderly women
      consumed 720 mg anthocyanins. A series of blood and urine samples were collected
      before and after consumption of the anthocyanins. Anthocyanins were measured in
      plasma and urine by combining an octadecylsilane solid-phase extraction for
      sample preparation and an HPLC system with diode array for anthocyanin separation
      and detection. The structures of anthocyanins as glycosides in plasma and urine
      were further confirmed by using liquid chromatography-mass spectrometry. RESULTS:
      Anthocyanins were detected as glycosides in plasma and urine. The maximum plasma
      concentration of total anthocyanins varied from 55.3 to 168.3 nmol/L, with an
      average of 97.4 nmol/L, and was reached within 71.3 min. The elimination of
      plasma anthocyanins appeared to follow first-order kinetics. The elimination half
      life of plasma total anthocyanins was calculated to be 132.6 min. Most
      anthocyanin compounds were excreted in urine during the first 4 h. The excretion
      rate of total anthocyanins was 77 microg/h during the first 4 h and 13 microg/h
      during the second 4 h. CONCLUSION: Anthocyanins are absorbed in their unchanged
      glycated forms in elderly women.

PMID- 11333847
TI  - Hyperhomocysteinemia associated with poor recall in the third National Health and
      Nutrition Examination Survey.
AB  - BACKGROUND: High circulating total homocysteine (tHcy) concentrations are
      associated with stroke, which is a major cause of cognitive dysfunction. Blood
      homocysteine concentrations are inversely correlated with performance on some
      cognitive-function tests and a relation was recently shown between
      hyperhomocysteinemia and Alzheimer disease. OBJECTIVE: The objective was to
      evaluate the relation between serum tHcy concentrations and performance on short
      delayed-recall tests of elderly men and women participating in the third National
      Health and Nutrition Examination Survey, phase 2 (1991--1994). DESIGN: Subjects
      were aged > or =60 y. Subjects reported no previous stroke, completed > or =8 y
      of education, and took a test of delayed recall of story ideas (n = 1200) or
      words (n = 1270). RESULTS: After adjustment for sex, age, race-ethnicity, income,
      years of education, and serum creatinine concentration, subjects in the upper
      half of the folate distribution recalled, on average, >4 of 6 story ideas;
      subjects with lower folate status recalled significantly fewer ideas (P < 0.001).
      Of the subjects with low folate status, story recall was significantly poorer in
      those with serum tHcy concentrations above the 80th percentile of the
      distribution (13.7 micromol/L) than in those with lower tHcy concentrations (P <
      0.03). The odds ratio relating hyperhomocysteinemia to recall of > or =1 of 3
      previously learned words was 0.3 (95% CI: 0.2, 0.7) after adjustment for the 5
      demographic factors alone and was 0.4 (0.2, 0.9) after further adjustment for
      serum folate concentration. CONCLUSION: Hyperhomocysteinemia is related to poor
      recall and this association was partially independent of folate status.

PMID- 11333848
TI  - Serum retinyl esters are not associated with biochemical markers of liver
      dysfunction in adult participants in the third National Health and Nutrition
      Examination Survey (NHANES III), 1988--1994.
AB  - BACKGROUND: Serum retinyl ester concentrations are elevated in hypervitaminosis
      A. It was suggested that retinyl esters >10% of total serum vitamin A indicate
      potential hypervitaminosis, but this cutoff was derived from small clinical
      samples that may not be representative of the general population. OBJECTIVE: We
      sought to examine the distribution of serum retinyl ester concentrations and
      associations between retinyl ester concentrations and biochemical markers of
      liver dysfunction in a nationally representative sample. DESIGN: We assessed the
      associations between serum retinyl ester concentrations and 5 biochemical indexes
      of liver dysfunction by using multivariate linear and multiple logistic
      regression techniques and controlling for age, sex, use of supplements containing
      vitamin A, alcohol consumption, smoking status, and use of exogenous estrogens in
      6547 adults aged > or =18 y in the third National Health and Nutrition
      Examination Survey (NHANES III), 1988--1994. RESULTS: Thirty-seven percent of the
      sample had serum retinyl ester concentrations >10% of total serum vitamin A and
      10% of the sample had serum retinyl esters >15% of total vitamin A. We found no
      associations between serum retinyl ester concentrations and 1) concentrations of
      any biochemical variable (multiple linear regression) or 2) risk of having
      biochemical variables above the reference range (multiple logistic regression).
      We did not find a serum retinyl ester value with statistically significant
      sensitivity and specificity for predicting increases in biochemical indexes of
      liver dysfunction. CONCLUSIONS: The prevalence of serum retinyl ester
      concentrations >10% of the total vitamin A concentration in the NHANES III sample
      was substantially higher than expected but elevated retinyl ester concentrations
      were not associated with abnormal liver function.

PMID- 11333849
TI  - Effect of plasma metabolites of (+)-catechin and quercetin on monocyte adhesion
      to human aortic endothelial cells.
AB  - BACKGROUND: Flavonoids may exert their health benefit in cardiovascular disease
      by modulating monocyte adhesion in the inflammatory process of atherosclerosis.
      Most in vitro studies used forms of flavonoids present in food rather than forms
      that appear in plasma after ingestion. OBJECTIVES: We tested the effects of
      plasma metabolites of (+)-catechin and quercetin on the modulation of monocyte
      adhesion to human aortic endothelial cells (HAEC) and on the production of
      reactive oxygen species (ROS). DESIGN: Plasma extracts of flavonoid metabolites
      were prepared after intragastric administration of pure compounds to rats. The
      plasma preparations contained sulfate or glucuronide conjugates or both and
      methylated forms. We measured adhesion of U937 monocytic cells to HAEC and the
      production of ROS in HAEC when cells were pretreated with either pure compounds
      or plasma extracts from control or treated rats. Adhesion assays were performed
      with HAEC stimulated with interleukin (IL)-1 beta or U937 cells activated with
      phorbol myristyl acetate; ROS were measured after challenging HAEC with IL-1 beta
      or hydrogen peroxide. RESULTS: Pretreatment of HAEC with (+)-catechin metabolites
      inhibited U937 cell adhesion to IL-1 beta-stimulated cells, whereas pretreatment
      with intact (+)-catechin had no effect. Generation of ROS in hydrogen peroxide
      stimulated HAEC was inhibited by (+)-catechin, its metabolites, and control
      plasma extract, whereas ROS generation in IL-1 beta-stimulated HAEC was inhibited
      by (+)-catechin metabolites only. In contrast, quercetin inhibited U937 cell
      adhesion to IL-1 beta-stimulated HAEC, whereas its metabolites were not
      effective. CONCLUSIONS: Metabolic conversion of flavonoids such as (+)-catechin
      and quercetin modifies the flavonoids' biological activity. Metabolites of
      flavonoids, rather than their intact forms, may contribute to the reported
      effects of flavonoids on reducing the risk of cardiovascular disease.

PMID- 11333850
TI  - Bioefficacy of beta-carotene dissolved in oil studied in children in Indonesia.
AB  - BACKGROUND: More information on the bioefficacy of carotenoids in foods ingested
      by humans is needed. OBJECTIVE: We aimed to measure the time required for
      isotopic enrichment of beta-carotene and retinol in serum to reach a plateau, the
      extent of conversion of beta-carotene dissolved in oil with use of beta-carotene
      and retinol specifically labeled with 10 (13)C atoms, and the intraindividual
      variation in response. DESIGN: Indonesian children aged 8--11 y (n = 35) consumed
      2 capsules/d, 7 d/wk, for < or =10 wk. Each capsule contained 80 microg
      [12,13,14,15,20,12',13',14',15',20'-(13)C(10)]beta-carotene and 80 microg
      [8,9,10,11,12,13,14,15,19,20-(13)C(10)]retinyl palmitate. Three blood samples
      were drawn per child over a period of < or =10 wk. HPLC coupled with atmospheric
      pressure chemical ionization liquid chromatography-mass spectrometry was used to
      measure the isotopic enrichment in serum of retinol with [(13)C(5)]retinol and
      [(13)C(10)]retinol and of beta-carotene with [(13)C(10)]beta-carotene. The beta
      carotene in the capsules used had a cis-trans ratio of 3:1. RESULTS: Plateau
      isotopic enrichment was reached by day 21. The amount of beta-carotene in oil
      required to form 1 microg retinol was 2.4 microg (95% CI: 2.1, 2.7). The amount
      of all-trans-beta-carotene required to form 1 microg retinol may be lower.
      CONCLUSIONS: The efficiency of conversion of this beta-carotene in oil was 27%
      better than that estimated previously (1.0 microg retinol from 3.3 microg beta
      carotene with an unknown cis-trans ratio). The method described can be extended
      to measure the bioefficacy of carotenoids in foods with high precision, requiring
      fewer subjects than other methods.

PMID- 11333851
TI  - Breast-feeding is associated with improved growth in length, but not weight, in
      rural Senegalese toddlers.
AB  - BACKGROUND: Prolonged breast-feeding is frequently associated with malnutrition
      in less-developed countries, even after adjustment for socioeconomic confounders.
      However, in rural Senegal, breast-feeding is prolonged when the child is stunted.
      OBJECTIVE: We aimed to test whether the lower height-for-age of children weaned
      late is explained by their height before weaning or whether prolonged breast
      feeding is associated with impaired growth. DESIGN: A cohort of 443 Senegalese
      children recruited from dispensaries at 2 mo of age were visited in their homes
      at 6-mo intervals when they were approximately 1.5 to 3 y of age. Weight, length,
      arm circumference, and triceps skinfold thickness were measured. Six-month
      increments were analyzed in relation to breast-feeding (breast-fed compared with
      weaned children or breast-feeding duration), season, and maternal housing with
      use of multiple linear regression. RESULTS: The mean duration of breast-feeding
      was 24.1 mo (quartiles 1 and 3: 21.9 and 26.4). Height-for-age at the age of 3 y
      was negatively associated with age at weaning (P < 0.01), but this association
      disappeared after adjustment for height-for-age in infancy. Length increments
      were significantly greater in both the second and third years of life in children
      breast-fed for longer durations (P < 0.05) and tended to be greater in breast-fed
      than in weaned children in the second year of life (P = 0.05). In the third year
      of life, breast-fed children had greater length increments than did weaned
      children in the subgroup with poor housing (P for interaction < 0.05). Growth in
      weight did not differ significantly according to breast-feeding. CONCLUSION:
      Prolonged breast-feeding improved linear growth, and the negative relation
      between height-for-age and duration of breast-feeding was due to reverse
      causality.

PMID- 11333852
TI  - Community-based controlled trial of dietary management of children with
      persistent diarrhea: sustained beneficial effect on ponderal and linear growth.
AB  - BACKGROUND: Uncontrolled hospital-based studies in developing countries have
      reported promising results of dietary rehabilitation of children with persistent
      diarrhea. OBJECTIVE: The objective was to determine the immediate and long-term
      effects of a dietary supplement and micronutrients given to children with
      persistent diarrhea during the episode and for 1 wk during convalescence. DESIGN:
      The study was open, controlled, and community-based and was conducted in a
      periurban area in Guinea-BISSAU: Children <3 y of age with persistent diarrhea
      were identified during weekly household visits. The children randomly assigned to
      the treatment and control groups were examined by a physician and all medical
      conditions were treated. The children in the treatment group were offered home
      based dietary treatment consisting of locally available foods and micronutrient
      supplements. RESULTS: There were 141 episodes of persistent diarrhea during the
      study: 70 in the treatment group (in 58 children) and 71 in the control group (in
      62 children). During the intervention period (median: 17 d), weight gain in the
      treatment group exceeded that of the control group by 61.5 g/wk (95% CI: 49.2,
      73.8), whereas there was no significant difference in linear growth on the basis
      of knee-heel length. At a median follow-up period of 6.6 mo after the
      intervention was stopped, weight gain in the treatment group exceeded that of the
      control group by 12.5 g/wk (95% CI: 7.7, 17.3); knee-heel length was 7.5 mm/y
      (4.8, 10.2) greater and total length was 0.65 cm/y (0.11, 1.19) greater in the
      treatment group. CONCLUSION: Therapeutic feeding and micronutrient
      supplementation had an immediate and sustained beneficial effect on growth in
      children with persistent diarrhea.

PMID- 11333853
TI  - Effect of hypoenergetic feeding and refeeding on muscle and mononuclear cell
      activities of mitochondrial complexes I--IV in enterally fed rats.
AB  - BACKGROUND: Previous studies suggested that cell energetics are altered by
      malnutrition. OBJECTIVE: We hypothesized that nutritional manipulations influence
      mitochondrial enzyme activities of the electron transport chain in both skeletal
      muscle and blood mononuclear cells. DESIGN: After a gastrostomy tube was
      inserted, 44 rats were randomly assigned to 1 of 4 experimental groups: control
      fed (CF; 364 kJ/d for 7 d), hypoenergetic fed (HF; 92 kJ/d for 7 d),
      hypoenergetic protein refed (HPR; 92 kJ/d for 7 d and then 129 kJ/d for 1 d), and
      hypoenergetic glucose refed (HGR; 92 kJ/d for 7 d and then 129 kJ/d for 1 d). The
      protein and glucose contents of the liquid formulas were different for the HPR
      and HGR groups. After mitochondria were isolated from the soleus muscle, the
      activities of complexes I--IV were measured spectrophotometrically. Because of
      the lack of available tissue, only the activity of complex I was measured in the
      mononuclear cell extract. RESULTS: The recovery of complex activities in the CF
      and HF groups was not significantly different in the mitochondrial fraction of
      the soleus muscle. Compared with that in the CF group, the activities of
      complexes I--III in the mitochondrial fraction of the soleus muscle and the
      activity of complex I in mononuclear cells were significantly lower in the HF
      group. The activities of complexes I--III in the mitochondrial fraction of the
      soleus muscle and the activity of complex I in mononuclear cells were
      significantly higher in the HPR than in the HF group. The activity of complex IV
      was generally not affected by nutritional manipulations. CONCLUSION: Malnutrition
      decreases activities of mitochondrial complexes, which are restored by protein
      but not glucose refeeding.

PMID- 11333854
TI  - Purification and quantification of lactoperoxidase in human milk with use of
      immunoadsorbents with antibodies against recombinant human lactoperoxidase.
AB  - BACKGROUND: Two heme-containing peroxidases, secretory lactoperoxidase and
      leukocyte-derived myeloperoxidase, which play host defense roles through
      antimicrobial activity, were previously identified in human colostrum. Within
      several days after the start of lactation, the relative contribution of
      myeloperoxidase to the peroxidase activity in milk was shown to decline as the
      number of milk leukocytes decreased. OBJECTIVE: Our knowledge of lactoperoxidase
      in human milk is still limited. The objective of this study was to use specific
      antibodies as a means of simplifying the purification and quantification of
      lactoperoxidase. DESIGN: Polyclonal antibodies were raised against recombinant
      human lactoperoxidase. Immunoglobulin G (IgG) was isolated by means of a protein
      A column and was characterized by immunoblotting. For the purification of
      lactoperoxidase from whey, a cation-exchange column and an immunoaffinity column
      with coupled IgG were used. The concentration of lactoperoxidase was determined
      by a sandwich enzyme-linked immunosorbent assay by using purified native
      lactoperoxidase as a standard. Native and biotinylated IgG were used as capture
      and detector antibodies, respectively. RESULTS: Two bands with molecular masses
      of approximately 80 and 100 kDa were detected in an immunoblot of human whey.
      Similar heterogeneity was observed in the sodium dodecyl sulfate-polyacrylamide
      gel electophoresis profile of purified lactoperoxidase. The mean (+/-SD)
      concentration of lactoperoxidase in 26 whey samples was estimated to be 0.77 +/-
      0.38 mg/L. The concentrations were positively correlated with the peroxidase
      activity detected in these samples. CONCLUSION: Lactoperoxidase is commonly
      present in human milk throughout the lactation period and is likely to contribute
      to the protective effects of milk.

PMID- 11333855
TI  - Dietary protein and intestinal calcium absorption.

PMID- 11333857
TI  - Hyperhomocysteinemia and cardiovascular disease.

PMID- 11333858
TI  - Predictive equations for skeletal muscle mass.

PMID- 11333865
TI  - A novel acropectoral syndrome maps to chromosome 7q36.
AB  - F syndrome (acropectorovertebral syndrome) is a dominantly inherited skeletal
      dysplasia affecting the hands, feet, sternum, and lumbosacral spine, which has
      previously been described in only two families. Here we report a six generation
      Turkish family with a related but distinct dominantly inherited acropectoral
      syndrome. All 22 affected subjects have soft tissue syndactyly of all fingers and
      all toes and 14 also have preaxial polydactyly of the hands and/or feet. In
      addition, 14 have a prominent upper sternum and/or a blind ending, inverted U
      shaped sinus in the anterior chest wall. Linkage studies and haplotype analysis
      carried out in 16 affected and nine unaffected members of this family showed that
      the underlying locus maps to a 6.4 cM interval on chromosome 7q36, between EN2
      and D7S2423, a region to which a locus for preaxial polydactyly and triphalangeal
      thumb-polysyndactyly has previously been mapped. Our findings expand the range of
      phenotypes associated with this locus to include total soft tissue syndactyly and
      sternal deformity, and suggest that F syndrome may be another manifestation of
      the same genetic entity. In mice, ectopic expression of the gene Sonic hedgehog
      (Shh) in limb buds and lateral plate mesoderm during development causes preaxial
      polydactyly and sternal defects respectively, suggesting that misregulation of
      SHH may underlie the unusual combination of abnormalities in this family. A
      recently proposed candidate gene for 7q36 linked preaxial polydactyly is LMBR1,
      encoding a novel transmembrane receptor which may be an upstream regulator of
      SHH.

PMID- 11333866
TI  - The mannose binding lectin gene influences the severity of chronic liver disease
      in cystic fibrosis.
AB  - Chronic liver disease is a major complication of cystic fibrosis. Its incidence
      and severity show marked heterogeneity, even among the homogeneous group of
      homozygous DeltaF508 patients, suggesting that environmental or genetic factors
      other than the deletion DeltaF508 may influence the development of cystic
      fibrosis related liver disease. We investigated whether the allelic variants of
      mannose binding lectin, an important protein of the immune system, could be
      associated with the presence of cirrhosis in a population of 216 homogeneous
      homozygous DeltaF508 patients. Analysis of the data shows that the presence of
      cirrhosis in cystic fibrosis patients is significantly associated with a mutated
      mannose binding lectin genotype (homozygous or compound heterozygous for mannose
      binding lectin variants). The modulating role of mannose binding lectin in the
      occurrence of cirrhosis in cystic fibrosis could be explained by the fact that
      hepatotoxic damage from viruses or bacteria might be increased by the
      immunodeficiency associated with mannose binding lectin variants and might
      facilitate the degradation of liver status. These data highlight the crucial role
      of mannose binding lectin in the clinical outcome of cystic fibrosis, as it has
      recently been shown that the mannose binding lectin gene is a modulating gene of
      the respiratory involvement in cystic fibrosis patients.

PMID- 11333867
TI  - Heterogeneous tissue distribution of a mitochondrial DNA polymorphism in
      heteroplasmic subjects without mitochondrial disorders.
AB  - CONTEXT: Several maternally inherited point mutations of the mitochondrial genome
      cause mitochondrial disorders, but the correlation between genotype and phenotype
      remains obscure in many cases. The same mutation may cause various diseases,
      probably because of a different tissue distribution. OBJECTIVE: To assess the
      role of random somatic segregation in generating interperson differences by
      analysis of an apparently neutral polymorphism. DESIGN: Screening of 81 brain
      samples from subjects without mitochondrial disorders and selection of five
      necropsy cases showing a high level of heteroplasmy for the polymorphism. MAIN
      OUTCOME MEASURES: A proportion of various distinct genotypes in the mtDNA pool of
      the tissues, identified by fluorescent PCR products, representing a short
      polycytosine tract of variable length in the mitochondrial displacement loop.
      RESULTS: Differences were found between organs or groups of organs within
      subjects, pointing towards somatic segregation of mtDNA. In addition, marked
      differences of this organ distribution occurred between subjects, which cannot be
      explained by tissue specific selection. CONCLUSIONS: The observed interperson
      differences can be explained by somatic segregation, which occurs randomly at
      various developmental stages. Besides tissue specific selection, this process
      might participate in the distribution of pathogenic mtDNA mutations.

PMID- 11333868
TI  - Atypical HNPCC owing to MSH6 germline mutations: analysis of a large Dutch
      pedigree.
AB  - Hereditary non-polyposis colorectal cancer (HNPCC) is the most common genetic
      susceptibility syndrome for colorectal cancer. HNPCC is most frequently caused by
      germline mutations in the DNA mismatch repair (MMR) genes MSH2 and MLH1.
      Recently, mutations in another MMR gene, MSH6 (also known as GTBP), have also
      been shown to result in HNPCC. Preliminary data indicate that the phenotype
      related to MSH6 mutations may differ from the classical HNPCC caused by defects
      in MSH2 and MLH1. Here, we describe an extended Dutch HNPCC family not fulfilling
      the Amsterdam criteria II and resulting from a MSH6 mutation. Overall, the
      penetrance of colorectal cancer appears to be significantly decreased (p<0.001)
      among the MSH6 mutation carriers in this family when compared with MSH2 and MLH1
      carriers (32% by the age of 80 v >80%). Endometrial cancer is a frequent
      manifestation among female carriers (six out of 13 malignant tumours).
      Transitional cell carcinoma of the urinary tract is also relatively common in
      both male and female carriers (10% of the carriers). Moreover, the mean age of
      onset of both colorectal cancer (MSH6 v MSH2/MLH1 = 55 years v 44/41 years) and
      endometrial carcinomas (MSH6 v MSH2/MLH1 = 55 years v 49/48 years) is delayed. As
      previously reported, we confirm that the pattern of microsatellite instability,
      in combination with immunohistochemical analysis, can predict the presence of a
      MSH6 germline defect. The detailed characterisation of the clinical phenotype of
      this kindred contributes to the establishment of genotype-phenotype correlations
      in HNPCC owing to mutations in specific mismatch repair genes.

PMID- 11333870
TI  - Does Bardet-Biedl syndrome have a characteristic face?

PMID- 11333869
TI  - A cysteine substitution in the zona pellucida domain of alpha-tectorin results in
      autosomal dominant, postlingual, progressive, mid frequency hearing loss in a
      Spanish family.

PMID- 11333864
TI  - Methylation matters.
AB  - DNA methylation is not just for basic scientists any more. There is a growing
      awareness in the medical field that having the correct pattern of genomic
      methylation is essential for healthy cells and organs. If methylation patterns
      are not properly established or maintained, disorders as diverse as mental
      retardation, immune deficiency, and sporadic or inherited cancers may follow.
      Through inappropriate silencing of growth regulating genes and simultaneous
      destabilisation of whole chromosomes, methylation defects help create a chaotic
      state from which cancer cells evolve. Methylation defects are present in cells
      before the onset of obvious malignancy and therefore cannot be explained simply
      as a consequence of a deregulated cancer cell. Researchers are now able to detect
      with exquisite sensitivity the cells harbouring methylation defects, sometimes
      months or years before the time when cancer is clinically detectable.
      Furthermore, aberrant methylation of specific genes has been directly linked with
      the tumour response to chemotherapy and patient survival. Advances in our ability
      to observe the methylation status of the entire cancer cell genome have led us to
      the unmistakable conclusion that methylation abnormalities are far more prevalent
      than expected. This methylomics approach permits the integration of an ever
      growing repertoire of methylation defects with the genetic alterations catalogued
      from tumours over the past two decades. Here we discuss the current knowledge of
      DNA methylation in normal cells and disease states, and how this relates directly
      to our current understanding of the mechanisms by which tumours arise.

PMID- 11333871
TI  - Multiple metachromatic leucodystrophy alleles in an unaffected subject: a case of
      dispermic chimaerism.

PMID- 11333872
TI  - The importance of good images in using hair to screen for breast cancer.

PMID- 11333874
TI  - Kinetics of murine gammaherpesvirus 68 gene expression following infection of
      murine cells in culture and in mice.
AB  - A model system to study the pathogenesis of gammaherpesvirus infections is the
      infection of mice with murine gammaherpesvirus 68 (MHV-68). To define the
      kinetics of infection, we developed an RNase protection assay to quantitate gene
      expression from lytic (K3, Rta, M8, DNA polymerase [DNA pol], and gB) and
      candidate latency (M2, M3, M9, M11, ORF73, and ORF74) genes. All candidate
      latency genes were expressed during lytic infection of 3T3 cells. Four kinetic
      classes of transcripts were observed following infection of 3T3 cells: immediate
      early (K3, Rta, M8, and ORF73), early (DNA pol), early-late (M3, M11, and ORF74),
      and late (M2, M9, and gB). To assess the kinetics of viral gene expression in
      vivo, lungs, spleens, and mediastinal lymph nodes (MLN) were harvested from MHV
      68-infected mice. All transcripts were expressed between 3 and 6 days
      postinfection (dpi) in the lungs. In the spleen, K3, M3, M8, and M9 transcripts
      were expressed between 10 and 16 dpi when latency is established. The K3, M3, M8,
      M9, and M11 transcripts were detected in the MLN from 2 through 16 dpi. This is
      the first demonstration of MHV-68 gene expression in the MLN. Importantly, our
      data showed that MHV-68 has different kinetics of gene expression at different
      sites of infection. Furthermore, we demonstrated that K3, a gene recently shown
      to encode a protein that downregulates major histocompatibility complex class I
      on the surface of cells, is expressed during latency, which argues for a role of
      K3 in immune evasion during latent infection.

PMID- 11333875
TI  - Construction and analysis of an infectious human Immunodeficiency virus type 1
      subtype C molecular clone.
AB  - Human immunodeficiency virus type 1 (HIV-1) subtype C is now the predominant
      subtype in the global epidemic. This subtype is encountered in southern Africa
      and parts of Asia, where the epidemic is rapidly spreading. One possible
      explanation for these epidemiological observations is that this subtype has
      genetic characteristics that may contribute to its spread and/or pathogenic
      potential. In this report, we describe the construction of MJ4, an infectious
      chimeric molecular clone of HIV-1 subtype C that replicates in donor peripheral
      blood mononuclear cells and macrophages. We also tested this clone for its
      ability to use the chemokine receptors CCR1, CCR2b, CCR3, CXCR4, and CCR5 and
      found that the clone utilizes only CCR5 as the coreceptor for cell entry. The MJ4
      clone will be useful in further biological and virological characterization of
      HIV-1 subtype C and will be an important tool in the continuing efforts to
      understand what may constitute protective immunity in HIV-1. The clone may also
      be used in experimental design of vaccine candidates that may be directed against
      HIV-1 subtype C.

PMID- 11333876
TI  - Adaptation of chimeric retroviruses in vitro and in vivo: isolation of avian
      retroviral vectors with extended host range.
AB  - We have designed and characterized two new replication-competent avian
      sarcoma/leukosis virus-based retroviral vectors with amphotropic and ecotropic
      host ranges. The amphotropic vector RCASBP-M2C(797-8), was obtained by passaging
      the chimeric retroviral vector RCASBP-M2C(4070A) (6) in chicken embryos. The
      ecotropic vector, RCASBP(Eco), was created by replacing the env-coding region in
      the retroviral vector RCASBP(A) with the env region from an ecotropic murine
      leukemia virus. It replicates efficiently in avian DFJ8 cells that express murine
      ecotropic receptor. For both vectors, permanent cell lines that produce viral
      stocks with titers of about 5 x 10(6) CFU/ml on mammalian cells can be easily
      established by passaging transfected avian cells. Some chimeric viruses, for
      example, RCASBP(Eco), replicate efficiently without modifications. For those
      chimeric viruses that do require modification, adaptation by passage in vitro or
      in vivo is a general strategy. This strategy has been used to prepare vectors
      with altered host range and could potentially be used to develop vectors that
      would be useful for targeted gene delivery.

PMID- 11333877
TI  - Kinetic analysis of the effect of poliovirus receptor on viral uncoating: the
      receptor as a catalyst.
AB  - We examined the role of soluble poliovirus receptor on the transition of native
      poliovirus (160S or N particle) to an infectious intermediate (135S or A
      particle). The viral receptor behaves as a classic transition state theory
      catalyst, facilitating the N-to-A conversion by lowering the activation energy
      for the process by 50 kcal/mol. In contrast to earlier studies which demonstrated
      that capsid-binding drugs inhibit thermally mediated N-to-A conversion through
      entropic stabilization alone, capsid-binding drugs are shown to inhibit receptor
      mediated N-to-A conversion through a combination of enthalpic and entropic
      effects.

PMID- 11333878
TI  - Identification of crucial hydrogen-bonding residues for the interaction of herpes
      simplex virus DNA polymerase subunits via peptide display, mutational, and
      calorimetric approaches.
AB  - The catalytic subunit, Pol, of herpes simplex virus DNA polymerase interacts via
      its extreme C terminus with the processivity subunit, UL42. This interaction is
      critical for viral replication and thus a potential target for antiviral drug
      action. To investigate the Pol-binding region on UL42, we engineered UL42
      mutations but also used random peptide display to identify artificial ligands of
      the Pol C terminus. The latter approach selected ligands with homology to
      residues 171 to 176 of UL42. Substitution of glutamine 171 with alanine greatly
      impaired binding to Pol and stimulation of long-chain DNA synthesis by Pol,
      identifying this residue as crucial for subunit interactions. To study these
      interactions quantitatively, we used isothermal titration calorimetry and wild
      type and mutant forms of Pol-derived peptides and UL42. Each of three peptides
      corresponding to either the last 36, 27, or 18 residues of Pol bound specifically
      to UL42 in a 1:1 complex with a dissociation constant of 1 to 2 microM. Thus, the
      last 18 residues suffice for most of the binding energy, which was due mainly to
      a change in enthalpy. Substitutions at positions corresponding to Pol residue
      1228 or 1229 or at UL42 residue 171 abolished or greatly reduced binding. These
      residues participate in hydrogen bonds observed in the crystal structure of the C
      terminus of Pol bound to UL42. Thus, interruption of these few bonds is
      sufficient to disrupt the interaction, suggesting that small molecules targeting
      the relevant side chains could interfere with Pol-UL42 binding.

PMID- 11333879
TI  - Genotypic correlates of phenotypic resistance to efavirenz in virus isolates from
      patients failing nonnucleoside reverse transcriptase inhibitor therapy.
AB  - Efavirenz (also known as DMP 266 or SUSTIVA) is a potent nonnucleoside inhibitor
      of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT)
      activity and of HIV-1 replication in vitro and in vivo. Most patients on
      efavirenz-containing regimens have sustained antiviral responses; however,
      rebounds in plasma viral load have been observed in some patients in association
      with the emergence of mutant strains of HIV-1. Virus isolates from the peripheral
      blood mononuclear cells (PBMCs) of patients with such treatment failures, as well
      as recombinant viruses incorporating viral sequences derived from patient plasma,
      show reduced in vitro susceptibility to efavirenz in association with mutations
      in the RT gene encoding K103N, Y188L, or G190S/E substitutions. Patterns of RT
      gene mutations and in vitro susceptibility were similar in plasma virus and in
      viruses isolated from PBMCs. Variant strains of HIV-1 constructed by site
      directed mutagenesis confirmed the role of K103N, G190S, and Y188L substitutions
      in reduced susceptibility to efavirenz. Further, certain secondary mutations
      (V106I, V108I, Y181C, Y188H, P225H, and F227L) conferred little resistance to
      efavirenz as single mutations but enhanced the level of resistance of viruses
      carrying these mutations in combination with K103N or Y188L. Viruses with K103N
      or Y188L mutations, regardless of the initial selecting nonnucleoside RT
      inhibitor (NNRTI), exhibited cross-resistance to all of the presently available
      NNRTIs (efavirenz, nevirapine, and delavirdine). Some virus isolates from
      nevirapine or delavirdine treatment failures that lacked K103N or Y188L mutations
      remained susceptible to efavirenz in vitro, although the clinical significance of
      this finding is presently unclear.

PMID- 11333880
TI  - Heterogeneous nuclear ribonucleoprotein a1 binds to the 3'-untranslated region
      and mediates potential 5'-3'-end cross talks of mouse hepatitis virus RNA.
AB  - The 3'-untranslated region (3'-UTR) of mouse hepatitis virus (MHV) RNA regulates
      the replication of and transcription from the viral RNA. Several host cell
      proteins have previously been shown to interact with this regulatory region. By
      immunoprecipitation of UV-cross-linked cellular proteins and in vitro binding of
      the recombinant protein, we have identified the major RNA-binding protein species
      as heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1). A strong hnRNP A1
      binding site was located 90 to 170 nucleotides from the 3' end of MHV RNA, and a
      weak binding site was mapped at nucleotides 260 to 350 from the 3' end. These
      binding sites are complementary to the sites on the negative-strand RNA that bind
      another cellular protein, polypyrimidine tract-binding protein (PTB). Mutations
      that affect PTB binding to the negative strand of the 3'-UTR also inhibited hnRNP
      A1 binding on the positive strand, indicating a possible relationship between
      these two proteins. Defective-interfering RNAs containing a mutated hnRNP A1
      binding site have reduced RNA transcription and replication activities.
      Furthermore, hnRNP A1 and PTB, both of which also bind to the complementary
      strands at the 5' end of MHV RNA, together mediate the formation of an RNP
      complex involving the 5'- and 3'-end fragments of MHV RNA in vitro. These studies
      suggest that hnRNP A1-PTB interactions provide a molecular mechanism for
      potential 5'-3' cross talks in MHV RNA, which may be important for RNA
      replication and transcription.

PMID- 11333881
TI  - Infectious entry by amphotropic as well as ecotropic murine leukemia viruses
      occurs through an endocytic pathway.
AB  - Infectious entry of enveloped viruses is thought to proceed by one of two
      mechanisms. pH-dependent viruses enter the cells by receptor-mediated endocytosis
      and are inhibited by transient treatment with agents that prevent acidification
      of vesicles in the endocytic pathway, while pH-independent viruses are not
      inhibited by such agents and are thought to enter the cell by direct fusion with
      the plasma membrane. Nearly all retroviruses, including amphotropic murine
      leukemia virus (MuLV) and human immunodeficiency virus type 1, are classified as
      pH independent. However, ecotropic MuLV is considered to be a pH-dependent virus.
      We have examined the infectious entry of ecotropic and amphotropic MuLVs and
      found that they were equally inhibited by NH4Cl and bafilomycin A. These agents
      inhibited both viruses only partially over the course of the experiments. Agents
      that block the acidification of endocytic vesicles also arrest vesicular
      trafficking. Thus, partial inhibition of the MuLVs could be the result of virus
      inactivation during arrest in this pathway. In support of this contention, we
      found that that the loss of infectivity of the MuLVs during treatment of target
      cells with the drugs closely corresponded to the loss of activity due to
      spontaneous inactivation at 37 degrees C in the same period of time. Furthermore,
      the drugs had no effect on the efficiency of infection under conditions in which
      the duration of infection was held to a very short period to minimize the effects
      of spontaneous inactivation. These results indicate that the infectious processes
      of both ecotropic and amphotropic MuLVs were arrested rather than aborted by
      transient treatment of the cells with the drugs. We also found that infectious
      viruses were efficiently internalized during treatment. This indicated that the
      arrest occurred in an intracellular compartment and that the infectious process
      of both the amphotropic and ecotropic MuLVs very likely involved endocytosis. An
      important aspect of this study pertains to the interpretation of experiments in
      which agents that block endocytic acidification inhibit infectivity. As we have
      found with the MuLVs, inhibition of infectivity may be secondary to the block of
      endocytic acidification. While this strongly suggests the involvement of an
      endocytic pathway, it does not necessarily indicate a requirement for an acidic
      compartment during the infectious process. Likewise, a lack of inhibition during
      transient treatment with the drugs would not preclude an endocytic pathway for
      viruses that are stable during the course of the treatment.

PMID- 11333882
TI  - Avian reovirus major mu-class outer capsid protein influences efficiency of
      productive macrophage infection in a virus strain-specific manner.
AB  - We determined that the highly pathogenic avian reovirus strain 176 (ARV-176)
      possesses an enhanced ability to establish productive infections in HD-11 avian
      macrophages compared to avian fibroblasts. Conversely, the weakly pathogenic
      strain ARV-138 shows no such macrophagotropic tendency. The macrophage infection
      capability of the two viruses did not reflect differences in the ability to
      either induce or inhibit nitric oxide production. Moderate increases in the ARV
      138 multiplicity of infection resulted in a concomitant increase in macrophage
      infection, and under such conditions the kinetics and extent of the ARV-138
      replication cycle were equivalent to those of the highly infectious ARV-176
      strain. These results indicated that both viruses are apparently equally capable
      of replicating in an infected macrophage, but they differ in the ability to
      establish productive infections in these cells. Using a genetic reassortant
      approach, we determined that the macrophagotropic property of ARV-176 reflects a
      post-receptor-binding step in the virus replication cycle and that the ARV-176 M2
      genome segment is required for efficient infection of HD-11 cells. The M2 genome
      segment encodes the major mu-class outer capsid protein (muB) of the virus, which
      is involved in virus entry and transcriptase activation, suggesting that a host
      specific influence on ARV entry and/or uncoating may affect the likelihood of the
      virus establishing a productive infection in a macrophage cell.

PMID- 11333883
TI  - Coadministration of gamma interferon with DNA vaccine expressing woodchuck
      hepatitis virus (WHV) core antigen enhances the specific immune response and
      protects against WHV infection.
AB  - DNA vaccinations are able to induce strong cellular immune responses in mice and
      confer protection against infectious agents. However, DNA vaccination of large
      animals appears to be less effective and requires repeated injections of large
      amounts of plasmid DNA. Enhancement of the efficiency of DNA vaccines may be
      achieved by coapplication of cytokine-expressing plasmids. Here we investigated,
      with woodchucks, whether coadministration of an expression plasmid for woodchuck
      gamma interferon (IFN-gamma), pWIFN-gamma, can improve DNA vaccination with
      woodchuck hepatitis virus core antigen (WHcAg). Animals were immunized with
      pWHcIm (a plasmid expressing WHcAg) alone or with a combination of pWHcIm and
      pWIFN-gamma using a gene gun. Six weeks postimmunization, all animals were
      challenged with 10(5) genome equivalents of woodchuck hepatitis virus (WHV). The
      antibody and lymphoproliferative immune responses to WHV proteins were determined
      after immunization and after challenge. Vaccination with pWHcIm and pWIFN-gamma
      led to a pronounced lymphoproliferative response to WHcAg and protected
      woodchucks against subsequent virus challenge. Two of three animals vaccinated
      with pWHcIm alone did not show a detectable lymphoproliferative response to
      WHcAg. A low-level WHV infection occurred in these woodchucks after challenge, as
      WHV DNA was detectable in the serum by PCR. None of the pWHcIm-vaccinated animals
      showed an anti-WHcAg antibody response after DNA vaccination or an anamnestic
      response after virus challenge. Our results indicate that coadministration of the
      WIFN-gamma gene with pWHcIm enhanced the specific cellular immune response and
      improved the protective efficacy of WHV-specific DNA vaccines.

PMID- 11333884
TI  - Incorporation of lysyl-tRNA synthetase into human immunodeficiency virus type 1.
AB  - During human immunodeficiency virus type 1 (HIV-1) assembly, tRNA(Lys)
      isoacceptors are selectively incorporated into virions and tRNA(Lys)3 is used as
      the primer for reverse transcription. We show herein that the tRNA(Lys)-binding
      protein, lysyl-tRNA synthetase (LysRS), is also selectively packaged into HIV-1.
      The viral precursor protein Pr55gag alone will package LysRS into Pr55gag
      particles, independently of tRNA(Lys). With the additional presence of the viral
      precursor protein Pr160gag-pol, tRNA(Lys) and LysRS are both packaged into the
      particle. While the predominant cytoplasmic LysRS has an apparent M(r) of 70,000,
      viral LysRS associated with tRNA(Lys) packaging is shorter, with an apparent M(r)
      of 63,000. The truncation occurs independently of viral protease and might be
      required to facilitate interactions involved in the selective packaging and
      genomic placement of primer tRNA.

PMID- 11333885
TI  - Virological properties and nucleotide sequences of Cas-E-type endogenous
      ecotropic murine leukemia viruses in South Asian wild mice, Mus musculus
      castaneus.
AB  - Two types of endogenous ecotropic murine leukemia viruses (MuLVs), termed AKV-
      and Cas-E-type MuLVs, differ in nucleotide sequence and distribution in wild
      mouse subspecies. In contrast to AKV-type MuLV, Cas-E-type MuLV is not carried by
      common laboratory mice. Wild mice of Mus musculus (M. m.) castaneus carry
      multiple copies of Cas-E-type endogenous MuLV, including the Fv-4(r) gene that is
      a truncated form of integrated MuLV and functions as a host's resistance gene
      against ecotropic MuLV infection. Our genetic cross experiments showed that only
      the Fv-4(r) gene was associated with resistance to ecotropic F-MuLV infection.
      Because the spontaneous expression of infectious virus was not detected in M. m.
      castaneus, we generated mice that did not carry the Fv-4(r) gene but did carry a
      single or a few endogenous MuLV loci. In mice not carrying the Fv-4(r) gene,
      infectious MuLVs were isolated in association with three of six Cas-E-type
      endogenous MuLV loci. The isolated viruses showed a weak syncytium-forming
      activity for XC cells, an interfering property of ecotropic MuLV, and a slight
      antigenic variation. Two genomic DNAs containing endogenous Cas-E-type MuLV were
      cloned and partially sequenced. All of the Cas-E-type endogenous MuLVs were
      closely related, hybrid-type viruses with an ecotropic env gene and a xenotropic
      long terminal repeat. Duplications and a deletion were found in a restricted
      region of the hypervariable proline-rich region of Env glycoprotein.

PMID- 11333886
TI  - Activation of TRAF5 and TRAF6 signal cascades negatively regulates the latent
      replication origin of Epstein-Barr virus through p38 mitogen-activated protein
      kinase.
AB  - Latent Epstein-Barr virus (EBV) is maintained by the virus replication origin
      oriP that initiates DNA replication with the viral oriP-binding factor EBNA1.
      However, it is not known whether oriP's replicator activity is regulated by virus
      proteins or extracellular signals. By using a transient replication assay, we
      found that a low level of expression of viral signal transduction activator
      latent membrane protein 1 (LMP1) suppressed oriP activity. The binding site of
      the tumor necrosis factor receptor-associated factor (TRAF) of LMP1 was essential
      for this suppressive effect. Activation of the TRAF signal cascade by
      overexpression of TRAF5 and/or TRAF6 also suppressed oriP activity. Conversely,
      blocking of TRAF signaling with dominant negative mutants of TRAF5 and TRAF6, as
      well as inhibition of a downstream signal mediator p38 MAPK, released the LMP1
      induced oriP suppression. Furthermore, activation of TRAF6 signal cascade by
      lipopolysaccharides (LPS) resulted in loss of EBV from Burkitt's lymphoma cell
      line Akata, and inhibition of p38 MAPK abolished the suppressive effect of LPS.
      These results suggested that the level of oriP activity is regulated by LMP1 and
      extracellular signals through TRAF5- and TRAF6-mediated signal cascades.

PMID- 11333887
TI  - Herpes simplex virus type 1 corneal infection results in periocular disease by
      zosteriform spread.
AB  - In humans and animal models of herpes simplex virus infection, zosteriform skin
      lesions have been described which result from anterograde spread of the virus
      following invasion of the nervous system. Such routes of viral spread have not
      been fully examined following corneal infection, and the possible pathologic
      consequences of such spread are unknown. To investigate this, recombinant viruses
      expressing reporter genes were generated to quantify and correlate gene
      expression with replication in eyes, trigeminal ganglia, and periocular tissue.
      Reporter activity peaked in eyes 24 h postinfection and rapidly fell to
      background levels by 48 h despite the continued presence of viral titers.
      Reporter activity rose in the trigeminal ganglia at 60 h and peaked at 72 h,
      concomitant with the appearance and persistence of infectious virus. Virus was
      present in the periocular skin from 24 h despite the lack of significant reporter
      activity until 84 h postinfection. This detection of reporter activity was
      followed by the onset of periocular disease on day 4. Corneal infection with a
      thymidine kinase-deleted reporter virus displayed a similar profile of reporter
      activity and viral titer in the eyes, but little or no detectable activity was
      observed in trigeminal ganglia or periocular tissue. In addition, no periocular
      disease symptoms were observed. These findings demonstrate that viral infection
      of periocular tissue and subsequent disease development occurs by zosteriform
      spread from the cornea to the periocular tissue via the trigeminal ganglion
      rather than by direct spread from cornea to the periocular skin. Furthermore,
      clinical evidence is discussed suggesting that a similar mode of spreading and
      disease occurs in humans following primary ocular infection.

PMID- 11333888
TI  - Rat cytomegalovirus major immediate-early enhancer switching results in altered
      growth characteristics.
AB  - It has been hypothesized that the major immediate-early (MIE) enhancer of
      cytomegalovirus (CMV) is important in determining virus tropism and latency
      because of its essential role in initiating the cascade of early gene expression
      necessary for virus replication. Although rat CMV (RCMV) and murine CMV (MCMV)
      exhibit extreme species specificity in vivo, they differ in their ability to
      replicate in tissue culture. MCMV can replicate in a rat embryo fibroblast (REF)
      cell line while RCMV does not grow in murine fibroblasts. The tropism is not due
      to a block in virus entry into the cell. We have constructed a recombinant RCMV
      in which the RCMV MIE enhancer has been replaced with that of MCMV. Growth of the
      recombinant virus in tissue culture remains restricted to rat cells, suggesting
      that other viral and/or host factors are more important in determining in vitro
      tropism. Unlike findings using recombinant MCMV in which the human CMV (HCMV) MIE
      enhancer substitutes for the native one (A. Angulo, M. Messerle, U. H.
      Koszinowski, and P. Ghazal, J. Virol. 72:8502-8509, 1998), infection with our
      recombinant virus at a low multiplicity of infection resulted in a substantial
      decrease in virus replication. This occurred despite comparable or increased MIE
      transcription from the recombinant virus. In vivo experiments showed that the
      recombinant virus replicates normally in the spleen during acute infection.
      Notably, the recombinant virus appears to be deficient in spreading to the
      salivary gland, suggesting a role for the MIE enhancer in tropism for certain
      tissues involved in virus dissemination. Four months after infection, recombinant
      virus with the foreign MIE enhancer was reactivated from spleen explants.

PMID- 11333889
TI  - Efficient infection of primary tupaia hepatocytes with purified human and woolly
      monkey hepatitis B virus.
AB  - The Asian tree shrew, Tupaia belangeri, has been proposed as a novel animal model
      for studying hepatitis B virus (HBV) infection. Here, we describe a protocol for
      efficient and reproducible infection of primary tupaia hepatocytes with HBV. We
      report that human serum interferes with HBV binding to the hepatocytes, thus
      limiting the maximum multiplicity of infection. Purification of HBV virions by
      gradient sedimentation greatly enhances virus binding and infectivity. Covalently
      closed circular DNA was clearly detectable by Southern blot analysis and newly
      synthesized single-stranded HBV DNA was visible 2 weeks postinoculation. Primary
      tupaia hepatocytes are also susceptible to infection with the recently discovered
      woolly monkey hepatitis B virus (WMHBV) but not to woodchuck hepatitis virus
      infection. Compared to HBV, WMHBV replicated at a higher rate with single
      stranded DNA detectable within the first week postinoculation. Primary tupaia
      hepatocytes should represent a useful system for studying early steps of HBV and
      WMHBV infection.

PMID- 11333890
TI  - Regulation of mRNA translation and cellular signaling by hepatitis C virus
      nonstructural protein NS5A.
AB  - The NS5A nonstructural protein of hepatitis C virus (HCV) has been shown to
      inhibit the cellular interferon (IFN)-induced protein kinase R (PKR). PKR
      mediates the host IFN-induced antiviral response at least in part by inhibiting
      mRNA translation initiation through phosphorylation of the alpha subunit of
      eukaryotic initiation factor 2 (eIF2alpha). We thus examined the effect of NS5A
      inhibition of PKR on mRNA translation within the context of virus infection by
      using a recombinant vaccinia virus (VV)-based assay. The VV E3L protein is a
      potent inhibitor of PKR. Accordingly, infection of IFN-pretreated HeLa S3 cells
      with an E3L-deficient VV (VVDeltaE3L) resulted in increased phosphorylation
      levels of both PKR and eIF2alpha. IFN-pretreated cells infected with VV in which
      the E3L locus was replaced with the NS5A gene (VVNS5A) displayed diminished
      phosphorylation of PKR and eIF2alpha in a transient manner. We also observed an
      increase in activation of p38 mitogen-activated protein kinase in IFN-pretreated
      cells infected with VVDeltaE3L, consistent with reports that p38 lies downstream
      of the PKR pathway. Furthermore, these cells exhibited increased phosphorylation
      of the cap-binding initiation factor 4E (eIF4E), which is downstream of the p38
      pathway. Importantly, these effects were reduced in cells infected with VVNS5A.
      NS5A was also found to inhibit activation of the p38-eIF4E pathway in epidermal
      growth factor-treated cells stably expressing NS5A. NS5A-induced inhibition of
      eIF2alpha and eIF4E phosphorylation may exert counteracting effects on mRNA
      translation. Indeed, IFN-pretreated cells infected with VVNS5A exhibited a
      partial and transient restoration of cellular and viral mRNA translation compared
      with IFN-pretreated cells infected with VVDeltaE3L. Taken together, these results
      support the role of NS5A as a PKR inhibitor and suggest a potential mechanism by
      which HCV might maintain global mRNA translation rate during early virus
      infection while favoring cap-independent translation of HCV mRNA during late
      infection.

PMID- 11333891
TI  - In vivo selection of a lymphocytic choriomeningitis virus variant that affects
      recognition of the GP33-43 epitope by H-2Db but not H-2Kb.
AB  - CD8 T cells drive the protective immune response to lymphocytic choriomeningitis
      virus (LCMV) infection and are thus a determining force in the selection of viral
      variants. To examine how escape mutations affect the presentation and recognition
      of overlapping T-cell epitopes, we isolated an LCMV variant that is not
      recognized by T-cell receptor (TCR)-transgenic H-2Db-restricted LCMV GP33-41
      specific cytotoxic T lymphocytes (CTL). The variant virus carried a single-amino
      acid substitution (valine to alanine) at position 35 of the viral glycoprotein.
      This region of the LCMV glycoprotein encodes both the Db-restricted GP33-43
      epitope and a second epitope (GP34-42) presented by the Kb molecule. We
      determined that the V-to-A CTL escape mutant failed to induce a Db GP33-43
      specific CTL response and that Db-restricted GP33-43-specific CTL induced by the
      wild-type LCMV strain were unable to kill target cells infected with the variant
      LCMV strain. In contrast, the Kb-restricted response was much less affected. We
      found that the V-to-A substitution severely impaired peptide binding to Db but
      not to Kb molecules. Strikingly, the V-to-A mutation did not change any of the
      anchor residues, and the dramatic effect on binding was therefore unexpected. The
      strong decrease in Db binding explains why the variant virus escapes the Db GP33
      43-specific response but still elicits the Kb-restricted response. These findings
      also illustrate that mutations within regions encoding overlapping T-cell
      epitopes can differentially affect the presentation and recognition of individual
      epitopes.

PMID- 11333892
TI  - Transfer of hepatitis B virus genome by adenovirus vectors into cultured cells
      and mice: crossing the species barrier.
AB  - For the study of hepatitis B virus infection, no permissive cell line or small
      animal is available. Stably transfected cell lines and transgenic mice which
      contain hepadnavirus genomes produce virus, but--unlike in natural infection-
      from an integrated viral transcription template. To transfer hepadnavirus genomes
      across the species barrier, we developed adenovirus vectors in which 1.3-fold
      overlength human and duck hepatitis B virus genomes were inserted. The adenovirus
      mediated genome transfer efficiently initiated hepadnavirus replication from an
      extrachromosomal template in established cell lines, in primary hepatocytes from
      various species, and in the livers of mice. Following the transfer, hepatitis B
      virus proteins, genomic RNA, and all replicative DNA intermediates were detected.
      Detection of covalently closed circular DNA in hepatoma cell lines and in primary
      hepatocytes indicated that an intracellular replication cycle independent from
      the transferred linear viral genome was established. High-titer hepatitis B
      virions were released into the culture medium of hepatoma cells and the various
      primary hepatocytes. In addition, infectious virions were secreted into the sera
      of mice. In conclusion, adenovirus-mediated genome transfer initiated efficient
      hepatitis B virus replication in cultured liver cells and in the experimental
      animals from an extrachromosomal template. This will allow development of small
      animal systems of hepatitis B virus infection and will facilitate study of
      pathogenicity of wild-type and mutant viruses as well as of virus-host
      interaction and new therapeutic approaches.

PMID- 11333893
TI  - Identification of major phosphorylation sites of Epstein-Barr virus nuclear
      antigen leader protein (EBNA-LP): ability of EBNA-LP to induce latent membrane
      protein 1 cooperatively with EBNA-2 is regulated by phosphorylation.
AB  - Epstein-Barr virus (EBV) nuclear antigen leader protein (EBNA-LP) is a
      phosphoprotein suggested to play important roles in EBV-induced immortalization
      of B cells. One of the potential functions of EBNA-LP is a cooperative induction
      with EBNA-2 of viral and cellular gene expression, including that of the genes
      for viral latent membrane protein 1 (LMP-1) and cellular cyclin D2. We report
      here that the phosphorylation of EBNA-LP by cellular kinase(s) is critical to its
      ability to cooperate with EBNA-2 in up-regulating the expression of LMP-1 in a B
      lymphoma cell line. Our conclusion is based on the following observations. (i)
      Mass-spectrometric analysis of purified EBNA-LP and mutational analyses of EBNA
      LP revealed that the serine residue at position 35 in the W2 repeat domain is the
      major phosphorylation site of EBNA-LP in vivo. (ii) Substitutions of this site in
      each W2 repeat domain with alanine markedly reduced the ability of the protein to
      induce LMP-1 expression in combination with EBNA-2 in Akata cells. (iii)
      Replacement at the major phosphorylation sites with glutamic acids restored the
      wild-type phenotype. It is well established that this substitution mimics
      constitutive phosphorylation. These results indicated that the coactivator
      function of EBNA-LP is regulated by phosphorylation.

PMID- 11333894
TI  - Primate and feline lentivirus vector RNA packaging and propagation by
      heterologous lentivirus virions.
AB  - Development of safe and effective gene transfer systems is critical to the
      success of gene therapy protocols for human diseases. Currently, several primate
      lentivirus-based gene transfer systems, such as those based on human and simian
      immunodeficiency viruses (HIV/SIV), are being tested; however, their use in
      humans raises safety concerns, such as the generation of replication-competent
      viruses through recombination with related endogenous retroviruses or retrovirus
      like elements. Due to the greater phylogenetic distance from primate
      lentiviruses, feline immunodeficiency virus (FIV) is becoming the lentivirus of
      choice for human gene transfer systems. However, the safety of FIV-based vector
      systems has not been tested experimentally. Since lentiviruses such as HIV-1 and
      SIV have been shown to cross-package their RNA genomes, we tested the ability of
      FIV RNA to get cross-packaged into primate lentivirus particles such as HIV-1 and
      SIV, as well as a nonlentiviral retrovirus such as Mason-Pfizer monkey virus
      (MPMV), and vice versa. Our results reveal that FIV RNA can be cross-packaged by
      primate lentivirus particles such as HIV-1 and SIV and vice versa; however, a
      nonlentivirus particle such as MPMV is unable to package FIV RNA. Interestingly,
      FIV particles can package MPMV RNA but cannot propagate the vector RNA further
      for other steps of the retrovirus life cycle. These findings reveal that diverse
      retroviruses are functionally more similar than originally thought and suggest
      that upon coinfection of the same host, cross- or copackaging may allow distinct
      retroviruses to generate chimeric variants with unknown pathogenic potential.

PMID- 11333895
TI  - Mucosal delivery of inactivated influenza vaccine induces B-cell-dependent
      heterosubtypic cross-protection against lethal influenza A H5N1 virus infection.
AB  - Influenza vaccines that induce greater cross-reactive or heterosubtypic immunity
      (Het-I) may overcome limitations in vaccine efficacy imposed by the antigenic
      variability of influenza A viruses. We have compared mucosal versus traditional
      parenteral administration of inactivated influenza vaccine for the ability to
      induce Het-I in BALB/c mice and evaluated a modified Escherichia coli heat-labile
      enterotoxin adjuvant, LT(R192G), for augmentation of Het-I. Mice that received
      three intranasal (i.n.) immunizations of H3N2 vaccine in the presence of
      LT(R192G) were completely protected against lethal challenge with a highly
      pathogenic human H5N1 virus and had nasal and lung viral titers that were at
      least 2,500-fold lower than those of control mice receiving LT(R192G) alone. In
      contrast, mice that received three vaccinations of H3N2 vaccine subcutaneously in
      the presence or absence of LT(R192G) or incomplete Freund's adjuvant were not
      protected against lethal challenge and had no significant reductions in tissue
      virus titers observed on day 5 post-H5N1 virus challenge. Mice that were i.n.
      administered H3N2 vaccine alone, without LT(R192G), displayed partial protection
      against heterosubtypic challenge. The immune mediators of Het-I were
      investigated. The functional role of B and CD8+ T cells in Het-I were evaluated
      by using gene-targeted B-cell (IgH-6(-/-))- or beta2-microglobulin (beta2m(-/-))
      deficient mice, respectively. beta2m(-/-) but not IgH-6(-/-) vaccinated mice were
      protected by Het-I and survived a lethal infection with H5N1, suggesting that B
      cells, but not CD8+ T cells, were vital for protection of mice against
      heterosubtypic challenge. Nevertheless, CD8+ T cells contributed to viral
      clearance in the lungs and brain tissues of heterotypically immune mice. Mucosal
      but not parenteral vaccination induced subtype cross-reactive lung immunoglobulin
      G (IgG), IgA, and serum IgG anti-hemagglutinin antibodies, suggesting the
      presence of a common cross-reactive epitope in the hemagglutinins of H3 and H5.
      These results suggest a strategy of mucosal vaccination that stimulates cross
      protection against multiple influenza virus subtypes, including viruses with
      pandemic potential.

PMID- 11333896
TI  - Reduction of simian-human immunodeficiency virus 89.6P viremia in rhesus monkeys
      by recombinant modified vaccinia virus Ankara vaccination.
AB  - Since cytotoxic T lymphocytes (CTLs) are critical for controlling human
      immunodeficiency virus type 1 (HIV-1) replication in infected individuals,
      candidate HIV-1 vaccines should elicit virus-specific CTL responses. In this
      report, we study the immune responses elicited in rhesus monkeys by a recombinant
      poxvirus vaccine and the degree of protection afforded against a pathogenic
      simian-human immunodeficiency virus SHIV-89.6P challenge. Immunization with
      recombinant modified vaccinia virus Ankara (MVA) vectors expressing SIVmac239 gag
      pol and HIV-1 89.6 env elicited potent Gag-specific CTL responses but no
      detectable SHIV-specific neutralizing antibody (NAb) responses. Following
      intravenous SHIV-89.6P challenge, sham-vaccinated monkeys developed low-frequency
      CTL responses, low-titer NAb responses, rapid loss of CD4+ T lymphocytes, high
      setpoint viral RNA levels, and significant clinical disease progression and death
      in half of the animals by day 168 postchallenge. In contrast, the recombinant MVA
      vaccinated monkeys demonstrated high-frequency secondary CTL responses, high
      titer secondary SHIV-89.6-specific NAb responses, rapid emergence of SHIV-89.6P
      specific NAb responses, partial preservation of CD4+ T lymphocytes, reduced
      setpoint viral RNA levels, and no evidence of clinical disease or mortality by
      day 168 postchallenge. There was a statistically significant correlation between
      levels of vaccine-elicited CTL responses prior to challenge and the control of
      viremia following challenge. These results demonstrate that immune responses
      elicited by live recombinant vectors, although unable to provide sterilizing
      immunity, can control viremia and prevent disease progression following a highly
      pathogenic AIDS virus challenge.

PMID- 11333897
TI  - Marek's disease virus (MDV) encodes an interleukin-8 homolog (vIL-8):
      characterization of the vIL-8 protein and a vIL-8 deletion mutant MDV.
AB  - Chemokines induce chemotaxis, cell migration, and inflammatory responses. We
      report the identification of an interleukin-8 (IL-8) homolog, termed vIL-8,
      encoded within the genome of Marek's disease virus (MDV). The 134-amino-acid vIL
      8 shares closest homology to mammalian and avian IL-8, molecules representing the
      prototype CXC chemokine. The gene for vIL-8 consists of three exons which map to
      the BamHI-L fragment within the repeats flanking the unique long region of the
      MDV genome. A 0.7-kb transcript encoding vIL-8 was detected in an n-butyrate
      treated, MDV-transformed T-lymphoblastoid cell line, MSB-1. This induction is
      essentially abolished by cycloheximide and herpesvirus DNA polymerase inhibitor
      phosphonoacetate, indicating that vIL-8 is expressed with true late (gamma2)
      kinetics. Baculovirus-expressed vIL-8 was found to be secreted into the medium
      and shown to be functional as a chemoattractant for chicken peripheral blood
      mononuclear cells but not for heterophils. To characterize the function of vIL-8
      with respect to MDV infection in vivo, a recombinant MDV was constructed with a
      deletion of all three exons and a soluble-modified green fluorescent protein
      (smGFP) expression cassette inserted at the site of deletion. In two in vivo
      experiments, the vIL-8 deletion mutant (RB1BvIL-8DeltasmGFP) showed a decreased
      level of lytic infection in comparison to its parent virus, an equal-passage
      level parent virus, and to another recombinant MDV containing the insertion of a
      GFP expression cassette at the nonessential US2 gene. RB1BvIL-8DeltasmGFP
      retained oncogenicity, albeit at a greatly reduced level. Nonetheless, we have
      been able to establish a lymphoblastoid cell line from an RB1BvIL-8DeltasmGFP
      induced ovarian lymphoma (MDCC-UA20) and verify the presence of a latent MDV
      genome lacking vIL-8. Taken together, these data describe the identification and
      characterization of a chemokine homolog encoded within the MDV genome that is
      dispensable for transformation but may affect the level of MDV in vivo lytic
      infection.

PMID- 11333898
TI  - Reduced expression of HLA class II molecules and Iinterleukin-10- and
      transforming growth factor beta1-independent suppression of T-cell proliferation
      in human cytomegalovirus-infected macrophage cultures.
AB  - After a primary infection, human cytomegalovirus (HCMV) establishes lifelong
      latency in myeloid lineage cells, and the virus has developed several mechanisms
      to avoid immune recognition and destruction of infected cells. In this study, we
      show that HCMV utilizes two different strategies to reduce the constitutive
      expression of HLA-DR, -DP, and -DQ on infected macrophages and that infected
      macrophages are unable to stimulate a specific CD4+ T-cell response.
      Downregulation of the HLA class II molecules was observed in 90% of the donor
      samples and occurred in two phases: at an early (1 day postinfection [dpi]) time
      point postinfection and at a late (4 dpi) time point postinfection. The early
      inhibition of HLA class II expression and antigen presentation was not dependent
      on active virus replication, since UV-inactivated virus induced downregulation of
      HLA-DR and inhibition of T-cell proliferation at 1 dpi. In contrast, the late
      effect required virus replication and was dependent on the expression of the HCMV
      unique short (US) genes US1 to -9 or US11 in 77% of the samples. HCMV-treated
      macrophages were completely devoid of T-cell stimulation capacity at 1 and 4 dpi.
      However, while downregulation of HLA class II expression was rather mild, a 66 to
      90% reduction in proliferative T-cell response was observed. This discrepancy was
      due to undefined soluble factors produced in HCMV-infected cell cultures, which
      did not include interleukin-10 and transforming growth factor beta1. These
      results suggest that HCMV reduces expression of HLA class II molecules on HCMV
      infected macrophages and inhibits T-cell proliferation by different distinct
      pathways.

PMID- 11333899
TI  - Identification of the regions of Fv1 necessary for murine leukemia virus
      restriction.
AB  - The Fv1 gene restricts murine leukemia virus replication via an interaction with
      the viral capsid protein. To study this interaction, a number of mutations,
      including a series of N-terminal and C-terminal deletions, internal deletions,
      and a number of single-amino-acid substitutions, were introduced into the n and b
      alleles of the Fv1 gene and the effects of these changes on virus restriction
      were measured. A significant fraction of the Fv1 protein was not required for
      restriction; however, retention of an intact major homology region as well as of
      domains toward the N and C termini was essential. Binding specificity appeared to
      be a combinatorial property of a number of residues within the C-terminal portion
      of Fv1.

PMID- 11333900
TI  - A herpes simplex virus type 1 gamma34.5 second-site suppressor mutant that
      exhibits enhanced growth in cultured glioblastoma cells is severely attenuated in
      animals.
AB  - We describe here the neurovirulence properties of a herpes simplex virus type 1
      gamma34.5 second-site suppressor mutant. gamma34.5 mutants are nonneurovirulent
      in animals and fail to grow in a variety of cultured cells due to a block at the
      level of protein synthesis. Extragenic suppressors with restored capacity to
      replicate in cells that normally do not support the growth of the parental
      gamma34.5 deletion mutant have been isolated. Although the suppressor virus
      reacquires the ability to grow in nonpermissive cultured cells, it remains
      severely attenuated in mice and is indistinguishable from the mutant gamma34.5
      parent virus at the doses investigated. Repairing the gamma34.5 mutation in the
      suppressor mutant restores neurovirulence to wild-type levels. These studies
      illustrate that (i) the protein synthesis and neurovirulence defects observed in
      gamma34.5 mutant viruses can be genetically separated by an extragenic mutation
      at another site in the viral chromosome; (ii) the extragenic suppressor mutation
      does not affect neurovirulence; and (iii) the attenuated gamma34.5 mutant, which
      replicates poorly in many cell types, can be modified by genetic selection to
      generate a nonpathogenic variant that regains the ability to grow robustly in a
      nonpermissive glioblastoma cell line. As this gamma34.5 second-site suppressor
      variant is attenuated and replicates vigorously in neoplastic cells, it may have
      potential as a replication-competent, viral antitumor agent.

PMID- 11333901
TI  - Human cytomegalovirus US2 endoplasmic reticulum-lumenal domain dictates
      association with major histocompatibility complex class I in a locus-specific
      manner.
AB  - The human cytomegalovirus-encoded US2 glycoprotein targets endoplasmic reticulum
      resident major histocompatibility complex (MHC) class I heavy chains for rapid
      degradation by the proteasome. We demonstrate that the endoplasmic reticulum
      lumenal domain of US2 allows tight interaction with class I molecules encoded by
      the HLA-A locus. Recombinant soluble US2 binds properly folded, peptide
      containing recombinant HLA-A2 molecules in a peptide sequence-independent manner,
      consistent with US2's ability to broadly downregulate class I molecules. The
      physicochemical properties of the US2/MHC class I complex suggest a 1:1
      stoichiometry. These results demonstrate that US2 does not require additional
      cellular proteins to specifically interact with soluble class I molecules.
      Binding of US2 does not significantly alter the conformation of class I
      molecules, as a soluble T-cell receptor can simultaneously recognize class I
      molecules associated with US2. The lumenal domain of US2 can differentiate
      between the products of distinct class I loci, as US2 binds several HLA-A locus
      products while being unable to bind recombinant HLA-B7, HLA-B27, HLA-Cw4, or HLA
      E. We did not observe interaction between soluble US2 and either recombinant HLA
      DR1 or recombinant HLA-DM. The substrate specificity of US2 may help explain the
      presence in human cytomegalovirus of multiple strategies for downregulation of
      MHC class I molecules.

PMID- 11333902
TI  - Ebola virus VP40-induced particle formation and association with the lipid
      bilayer.
AB  - Viral protein 40 (VP40) of Ebola virus appears equivalent to matrix proteins of
      other viruses, yet little is known about its role in the viral life cycle. To
      elucidate the functions of VP40, we investigated its ability to induce the
      formation of membrane-bound particles when it was expressed apart from other
      viral proteins. We found that VP40 is indeed able to induce particle formation
      when it is expressed in mammalian cells, and this process appeared to rely on a
      conserved N-terminal PPXY motif, as mutation or loss of this motif resulted in
      markedly reduced particle formation. These findings demonstrate that VP40 alone
      possesses the information necessary to induce particle formation, and this
      process most likely requires cellular WW domain-containing proteins that interact
      with the PPXY motif of VP40. The ability of VP40 to bind cellular membranes was
      also studied. Flotation gradient analysis indicated that VP40 binds to membranes
      in a hydrophobic manner, as NaCl at 1 M did not release the protein from the
      lipid bilayer. Triton X-114 phase-partitioning analysis suggested that VP40
      possesses only minor features of an integral membrane protein. We confirmed
      previous findings that truncation of the 50 C-terminal amino acids of VP40
      results in decreased association with cellular membranes and demonstrated that
      this deletion disrupts hydrophobic interactions of VP40 with the lipid bilayer,
      as well as abolishing particle formation. Truncation of the 150 C-terminal amino
      acids or 100 N-terminal amino acids of VP40 enhanced the protein's hydrophobic
      association with cellular membranes. These data suggest that VP40 binds the lipid
      bilayer in an efficient yet structurally complex fashion.

PMID- 11333903
TI  - Enhancement of adenovirus vector entry into CD70-positive B-cell Lines by using a
      bispecific CD70-adenovirus fiber antibody.
AB  - Although many recombinant adenovirus vectors (rAd) have been developed,
      especially by using group C adenoviruses, to transfer and express genes, such rAd
      do not readily infect B-cell lines due to the lack of the coxsackievirus
      adenovirus receptor. Bispecific antibodies have been used in different cell
      systems to facilitate entry of rAd into otherwise nonpermissive cells. Bispecific
      antibody is synthesized by covalently linking two monoclonal antibodies with
      distinct specificities. It has been shown that lymphoproliferative tumors
      commonly express the cell surface protein CD70, while this receptor is normally
      expressed on only a small subset of highly activated B cells and T cells. We
      therefore investigated whether a bispecific antibody with specificities for the
      adenovirus fiber protein and CD70 can facilitate rAd entry and subsequent
      expression of rAd-encoded genes in CD70-positive B cells. We found high CD70
      expression on Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines
      (LCLs), as well as some, but not all, Burkitt lymphoma (BL) lines. We show here
      that rAd encoding green fluorescent protein (Ad-GFP) infects EBV-transformed LCLs
      and a CD70-positive BL line 10- to 20-fold more efficiently in the presence of
      the CD70-fiber bispecific antibody. In contrast, the bispecific antibody does not
      enhance Ad-GFP infection in CD70-deficient BL cells. Using the CD70-fiber
      bispecific antibody, we increased the ability of rAd vectors encoding the EBV
      immediate-early proteins BZLF1 and BRLF1 to induce the lytic form of EBV
      infection in LCLs. These results indicate that the CD70-fiber bispecific antibody
      can enhance rAd infection of CD70-positive B cells and suggest the use of this
      vector to explore EBV-positive LCLs.

PMID- 11333904
TI  - Biology of E1-deleted adenovirus vectors in nonhuman primate muscle.
AB  - Adenovirus vectors have been studied as vehicles for gene transfer to skeletal
      muscle, an attractive target for gene therapies for inherited and acquired
      diseases. In this setting, immune responses to viral proteins and/or transgene
      products cause inflammation and lead to loss of transgene expression. A few
      studies in murine models have suggested that the destructive cell-mediated immune
      response to virally encoded proteins of E1-deleted adenovirus may not contribute
      to the elimination of transgene-expressing cells. However, the impact of immune
      responses following intramuscular administration of adenovirus vectors on
      transgene stability has not been elucidated in larger animal models such as
      nonhuman primates. Here we demonstrate that intramuscular administration of E1
      deleted adenovirus vector expressing rhesus monkey erythropoietin or growth
      hormone to rhesus monkeys results in generation of a Th1-dependent cytotoxic T
      cell response to adenovirus proteins. Transgene expression dropped significantly
      over time but was still detectable in some animals after 6 months. Systemic
      levels of adenovirus-specific neutralizing antibodies were generated, which
      blocked vector readministration. These studies indicate that the cellular and
      humoral immune response generated to adenovirus proteins, in the context of
      transgenes encoding self-proteins, hinders long-term transgene expression and
      readministration with first-generation vectors.

PMID- 11333905
TI  - Relationships between CD4 independence, neutralization sensitivity, and exposure
      of a CD4-induced epitope in a human immunodeficiency virus type 1 envelope
      protein.
AB  - A CD4-independent version of the X4 human immunodeficiency virus type 1 (HIV-1)
      HXBc2 envelope (Env) protein, termed 8x, mediates infection of CD4-negative,
      CXCR4-positive cells, binds directly to CXCR4 in the absence of CD4 due to
      constitutive exposure of a conserved coreceptor binding site in the gp120
      subunit, and is more sensitive to antibody-mediated neutralization. To study the
      relationships between CD4 independence, neutralization sensitivity, and exposure
      of CD4-induced epitopes associated with the coreceptor binding site, we generated
      a large panel of Env mutants and chimeras between 8x and its CD4-dependent
      parent, HXBc2. We found that a frameshift mutation just proximal to the gp41
      cytoplasmic domain in 8x Env was necessary but not sufficient for CD4
      independence and led to increased exposure of the coreceptor binding site. In the
      presence of this altered cytoplasmic domain, single amino acid changes in either
      the 8x V3 (V320I) or V4/C4 (N386K) regions imparted CD4 independence, with other
      changes playing a modulatory role. The N386K mutation resulted in loss of an N
      linked glycosylation site, but additional mutagenesis showed that it was the
      presence of a lysine rather than loss of the glycosylation site that contributed
      to CD4 independence. However, loss of the glycosylation site alone was sufficient
      to render Env neutralization sensitive, providing additional evidence that
      carbohydrate structures shield important neutralization determinants. Exposure of
      the CD4-induced epitope recognized by monoclonal antibody 17b and which overlaps
      the coreceptor binding site was highly sensitive to an R298K mutation at the base
      of the V3 loop and was often but not always associated with CD4 independence.
      Finally, while not all neutralization-sensitive Envs were CD4 independent, all
      CD4-independent Envs exhibited enhanced sensitivity to neutralization by HIV-1
      positive human sera, indicating that the humoral immune response can exert strong
      selective pressure against the CD4-independent phenotype in vivo. Whether this
      can be used to advantage in designing more effective immunogens remains to be
      seen.

PMID- 11333906
TI  - Autostimulation of the Epstein-Barr virus BRLF1 promoter is mediated through
      consensus Sp1 and Sp3 binding sites.
AB  - As an essential step in the lytic cascade, the Rta homologues of
      gammaherpesviruses all activate their own expression. Consistent with this
      biologic function, the Epstein-Barr virus (EBV) Rta protein powerfully stimulates
      the promoter of its own gene, Rp, in EBV-positive B cells in transient
      transfection reporter-based assays. We analyzed the activity of RpCAT in response
      to Rta by deletional and site-directed mutagenesis. Two cognate Sp1 binding sites
      located at -279 and -45 relative to the transcriptional start site proved crucial
      for Rta-mediated activation. Previously described binding sites for the cellular
      transcription factor Zif268 and the viral transactivator ZEBRA were found to be
      dispensable for activation of RpCAT by Rta. Gel shift analysis, using extracts of
      B cells in latency or induced into the lytic cycle, identified Sp1 and Sp3 as the
      predominant cellular proteins bound to Rp near -45. During the lytic cycle, ZEBRA
      bound Rp near the Sp1/Sp3 site. The binding of Sp1 and Sp3 to Rp correlated with
      the reporter activities in the mutagenesis study, establishing a direct link
      between transcriptional activation of Rp by Rta and DNA binding by Sp1 and/or
      Sp3. The relative abundance or functional state of the cellular Sp1 and Sp3
      transcription factors may be altered in response to stimuli that induce the BRLF1
      promoter and thereby contribute to the activation of the viral lytic cycle.

PMID- 11333907
TI  - Tracking the spread of a lacZ-tagged herpes simplex virus type 1 between the eye
      and the nervous system of the mouse: comparison of primary and recurrent
      infection.
AB  - The spread of herpes simplex virus type 1 (HSV-1) during primary ocular infection
      and after reactivation of latent infection in the trigeminal ganglion (TG) was
      examined in the mouse using a genetically modified virus containing the lacZ
      reporter gene under the control of the immediate-early 110 promoter. Whole tissue
      mounts of the eye and lids, their sensory nerves, and TG with the attached dorsal
      root entry zone (DRE) into the central nervous system (CNS) were stained for beta
      galactosidase. Sixteen hours after inoculation of the cornea by scarification,
      staining was found in the scarified epithelium of the cornea and in the
      unscarified conjunctiva. By 24 h, staining was also seen in a few TG neurons and
      by 96 h their number had greatly increased and their distribution was more
      widespread. Stained cells (identified as Schwann cells by their staining for
      glial fibrillary acidic protein [GFAP] or S-100) in the TG were first seen close
      to stained neurons at 40 h, and by 48 h lines of such cells extended partway
      toward the periphery and toward the DRE. By 72 h, these lines had reached the
      periphery and the DRE where the adjacent CNS was also stained. In the cornea,
      stained cells with the morphology and arrangement of Schwann cells were seen from
      40 to 120 h. After reactivation of latent infection, 10 of 22 samples had
      positively stained neurons. In eight samples, corneal and lid epithelial cells
      were stained. No stained Schwann cells were seen in the TG; however, branched
      networks of such cells were present in the cornea and the lids. This detailed
      sequential analysis has provided new information on the involvement of Schwann
      cells in the pathogenesis of primary and recurrent HSV-1 disease in the TG and
      the cornea.

PMID- 11333909
TI  - The NH2-terminal domain of the human T-cell leukemia virus type 1 capsid protein
      is involved in particle formation.
AB  - The human immunodeficiency virus type 1 (HIV-1) and human T-cell leukemia virus
      type 1 (HTLV-1) capsid proteins (CA) display similar structures formed by two
      independently folded N-terminal (NTD) and C-terminal (CTD) domains. To
      characterize the functions harbored by the HTLV-1 CA domains in particle
      formation, 12 sites scattered throughout the protein were mutated. The effects of
      the mutations on Gag membrane binding, proteolytic processing, and virus-like
      particle secretion were analyzed. It appears that the NTD is the major partner of
      indirect or direct Gag-Gag interactions. In particular, most of the NTD mutations
      impaired virion morphogenesis, and no mutation located in the NTD could be fully
      rescued by coexpression of wild-type Gag. In contrast, the CTD seems not to be
      involved in Gag-Gag interactions. Nevertheless, an unknown function required for
      particle formation is located in the CTD. Thus, despite an overall structural
      similarity between the HIV-1 and HTLV-1 CA proteins, their NTDs and CTDs exhibit
      different functions.

PMID- 11333908
TI  - Identification of two sequences in the cytoplasmic tail of the human
      immunodeficiency virus type 1 envelope glycoprotein that inhibit cell surface
      expression.
AB  - During synthesis and export of protein, the majority of the human
      immunodeficiency virus type 1 (HIV-1) Env glycoprotein gp160 is retained in the
      endoplasmic reticulum (ER) and subsequently ubiquitinated and degraded by
      proteasomes. Only a small fraction of gp160 appears to be correctly folded and
      processed and is transported to the cell surface, which makes it difficult to
      identify negative sequence elements regulating steady-state surface expression of
      Env at the post-ER level. Moreover, poorly localized mRNA retention sequences
      inhibiting the nucleocytoplasmic transport of viral transcripts interfere with
      the identification of these sequence elements. Using two heterologous systems
      with CD4 or immunoglobulin extracellular/transmembrane domains in combination
      with the gp160 cytoplasmic domain, we were able to identify two membrane-distal,
      neighboring motifs, is1 (amino acids 750 to 763) and is2 (amino acids 764 to
      785), which inhibited surface expression and induced Golgi localization of the
      chimeric proteins. To prove that these two elements act similarly in the
      homologous context of the Env glycoprotein, we generated a synthetic gp160 gene
      with synonymous codons, the transcripts of which are not retained within the
      nucleus. In accordance with the results in heterologous systems, an internal
      deletion of both elements considerably increased surface expression of gp160.

PMID- 11333910
TI  - Construction of avian adenovirus CELO recombinants in cosmids.
AB  - The avian adenovirus CELO is a promising vector for gene transfer applications.
      In order to study this potentiality, we developed an improved method for
      construction of adenovirus vectors in cosmids that was used to engineer the CELO
      genome. For all the recombinant viruses constructed by this method, the ability
      to produce infectious particles and the stability of the genome were evaluated in
      a chicken hepatocarcinoma cell line (LMH cell line). Our aim was to develop a
      replication-competent vector for vaccination of chickens, so we first generated
      knockout point mutations into 16 of the 22 unassigned CELO open reading frames
      (ORFs) to determine if they were essential for virus replication. As the 16
      independent mutant viruses replicated in our cellular system, we constructed CELO
      genomes with various deletions in the regions of these nonessential ORFs. An
      expression cassette coding for the enhanced green fluorescent protein (eGFP) was
      inserted in place of these deletions to easily follow expression of the transgene
      and propagation of the vector in cell monolayers. Height-distinct GFP-expressing
      CELO vectors were produced that were all replication competent in our system. We
      then retained the vector backbone with the largest deletion (i.e., 3.6 kb) for
      the construction of vectors carrying cDNA encoding infectious bursal disease
      virus proteins. These CELO vectors could be useful for vaccination in the chicken
      species.

PMID- 11333911
TI  - Polyomavirus small t antigen prevents retinoic acid-induced retinoblastoma
      protein hypophosphorylation and redirects retinoic acid-induced G0 arrest and
      differentiation to apoptosis.
AB  - Polyomavirus small t antigen (ST) impedes late features of retinoic acid (RA)
      induced HL-60 myeloid differentiation as well as growth arrest, causing apoptosis
      instead. HL-60 cells were stably transfected with ST. ST slowed the cell cycle,
      retarding G2/M in particular. Treated with RA, the ST transfectants continued to
      proliferate and underwent apoptosis. ST also impeded the normally RA-induced
      hypophosphorylation of the retinoblastoma tumor suppressor protein consistent
      with failure of the cells to arrest growth. The RA-treated transfectants
      expressed CD11b, an early cell surface differentiation marker, but inducible
      oxidative metabolism, a later and more mature functional differentiation marker,
      was largely inhibited. Instead, the cells underwent apoptosis. ST affected
      significant known components of RA signaling that result in G0 growth arrest and
      differentiation in wild-type HL-60. ST increased the basal amount of activated
      ERK2, which normally increases when wild-type cells are treated with RA. ST
      caused increased RARalpha expression, which is normally down regulated in RA
      treated wild-type cells. The effects of ST on RA-induced myeloid differentiation
      did not extend to monocytic differentiation and G0 arrest induced by 1,25
      dihydroxy vitamin D3, whose receptor is also a member of the steroid-thyroid
      hormone superfamily. In this case, ST abolished the usually induced G0 arrest and
      retarded, but did not block, differentiation without inducing apoptosis, thus
      uncoupling growth arrest and differentiation. In sum, the data show that ST
      disrupted the normal RA-induced program of G0 arrest and differentiation, causing
      the cells to abort differentiation and undergo apoptosis.

PMID- 11333912
TI  - Analysis of a novel strain of murine gammaherpesvirus reveals a genomic locus
      important for acute pathogenesis.
AB  - Infection of mice by murine gammaherpesvirus 68 (MHV-68) is an excellent small
      animal model of gammaherpesvirus pathogenesis in a natural host. We have carried
      out comparative studies of another herpesvirus, murine herpesvirus 76 (MHV-76),
      which was isolated at the same time as MHV-68 but from a different murid host,
      the yellow-necked mouse (Apodemus flavicollis). Molecular analyses revealed that
      the MHV-76 genome is essentially identical to that of MHV-68, except for deletion
      of 9,538 bp at the left end of the unique region. MHV-76 is therefore a deletion
      mutant that lacks four genes unique to MHV-68 (M1, M2, M3, and M4) as well as the
      eight viral tRNA-like genes. Replication of MHV-76 in cell culture was identical
      to that of MHV-68. However, following infection of mice, MHV-76 was cleared more
      rapidly from the lungs. In line with this, there was an increased inflammatory
      response in lungs with MHV-76. Splenomegaly was also significantly reduced
      following MHV-76 infection, and much less latent MHV-76 was detected in the
      spleen. Nevertheless, MHV-76 maintained long-term latency in the lungs and
      spleen. We utilized a cosmid containing the left end of the MHV-68 genome to
      reinsert the deleted sequence into MHV-76 by recombination in infected cells, and
      we isolated a rescuant virus designated MHV-76(cA8+)4 which was ostensibly
      genetically identical to MHV-68. The growth properties of the rescuant in
      infected mice were identical to those of MHV-68. These results demonstrate that
      genetic elements at the left end of the unique region of the MHV-68 genome play
      vital roles in host evasion and are critical to the development of splenic
      pathology.

PMID- 11333913
TI  - Efficient transmission of two different sheep scrapie isolates in transgenic mice
      expressing the ovine PrP gene.
AB  - We produced transgenic mice expressing the sheep prion protein to obtain a
      sensitive model for sheep spongiform encephalopathies (scrapie). The complete
      open reading frame, with alanine, arginine, and glutamine at susceptibility
      codons 136, 154, and 171, respectively, was inserted downstream from the neuron
      specific enolase promoter. A mouse line, Tg(OvPrP4), devoid of the murine PrP
      gene, was obtained by crossing with PrP knockout mice. Tg(OvPrP4) mice were shown
      to selectively express sheep PrP in their brains, as demonstrated in mRNA and
      protein analysis. We showed that these mice were susceptible to infection by
      sheep scrapie following intracerebral inoculation with two natural sheep scrapie
      isolates, as demonstrated not only by the occurrence of neurological signs but
      also by the presence of the spongiform changes and abnormal prion protein
      accumulation in their brains. Mean times to death of 238 and 290 days were
      observed with these isolates, but the clinical course of the disease was
      strikingly different in the two cases. One isolate led to a very early onset of
      neurological signs which could last for prolonged periods before death.
      Independently of the incubation periods, some of the mice inoculated with this
      isolate showed low or undetectable levels of PrPsc, as detected by both Western
      blotting and immunohistochemistry. The development of experimental scrapie in
      these mice following inoculation of the scrapie infectious agent further confirms
      that neuronal expression of the PrP open reading frame alone is sufficient to
      mediate susceptibility to spongiform encephalopathies. More importantly, these
      mice provide a new and promising tool for studying the infectious agents in sheep
      spongiform encephalopathies.

PMID- 11333915
TI  - Hepatitis B virus large envelope protein interacts with gamma2-adaptin, a
      clathrin adaptor-related protein.
AB  - For the outcome of a hepatitis B virus (HBV) infection, the viral L envelope
      protein with its pre-S domain performs pivotal functions by mediating attachment
      of HBV to liver cells, envelopment of viral capsids, release of (sub)viral
      particles, regulation of supercoiled DNA amplification, and transcriptional
      transactivation. To assess its multiple functions and host-protein assistance
      involved, we initiated a two-hybrid screen using the L-specific pre-S1 domain as
      bait. With this approach, we have identified gamma2-adaptin, a putative member of
      the clathrin adaptor proteins responsible for protein sorting and trafficking, as
      a specific binding partner of L protein. Evidence for a physical interaction
      between L protein and gamma2-adaptin was also demonstrated by affinity
      chromatography and coimmunoprecipitation, and the binding sites were mapped to
      the L-specific pre-S1 domain and the gamma2-adaptin-specific ear domain. The
      specificity of the interaction was further sustained by the failure of gamma1
      adaptin, a closely related gamma2-adaptin homologue, to associate with L protein.
      Analysis of an L mutant protein indicates that the L-gamma2-adaptin interaction
      strictly depends on the pre-S1 domain of transmembrane L protein oriented to the
      cytosol and thus appears to occur in the cytosolic environment. Interestingly,
      coexpression of the two interacting partners in transfected cells resulted in
      recruitment of gamma2-adaptin by L protein onto cis-Golgi-like structures,
      strongly indicating that the association is physiologically relevant. Together,
      the results suggest a role for gamma2-adaptin in L-mediated processes of viral
      biogenesis and/or pathogenesis, such as facilitating and guiding HBV assembly.

PMID- 11333914
TI  - Complete in vitro assembly of the reovirus outer capsid produces highly
      infectious particles suitable for genetic studies of the receptor-binding
      protein.
AB  - Mammalian reoviruses, prototype members of the Reoviridae family of nonenveloped
      double-stranded RNA viruses, use at least three proteins--sigma1, mu1, and sigma3
      -to enter host cells. sigma1, a major determinant of cell tropism, mediates viral
      attachment to cellular receptors. Studies of sigma1 functions in reovirus entry
      have been restricted by the lack of methodologies to produce infectious virions
      containing engineered mutations in viral proteins. To mitigate this problem, we
      produced virion-like particles by "recoating" genome-containing core particles
      that lacked sigma1, mu1, and sigma3 with recombinant forms of these proteins in
      vitro. Image reconstructions from cryoelectron micrographs of the recoated
      particles revealed that they closely resembled native virions in three
      dimensional structure, including features attributable to sigma1. The recoated
      particles bound to and infected cultured cells in a sigma1-dependent manner and
      were approximately 1 million times as infectious as cores and 0.5 times as
      infectious as native virions. Experiments with recoated particles containing
      recombinant sigma1 from either of two different reovirus strains confirmed that
      differences in cell attachment and infectivity previously observed between those
      strains are determined by the sigma1 protein. Additional experiments showed that
      recoated particles containing sigma1 proteins with engineered mutations can be
      used to analyze the effects of such mutations on the roles of particle-bound
      sigma1 in infection. The results demonstrate a powerful new system for molecular
      genetic dissections of sigma1 with respect to its structure, assembly into
      particles, and roles in entry.

PMID- 11333916
TI  - Characterization of the infectious salmon anemia virus genomic segment that
      encodes the putative hemagglutinin.
AB  - The genomic segment encoding the putative hemagglutinin of infectious salmon
      anemia virus (ISAV) is described. Expression of the putative hemagglutinin in a
      salmon cell line demonstrated hemadsorptive properties of the protein for salmon
      erythrocytes. The polypeptide was recognized by an ISAV-specific monoclonal
      antibody. Nucleotide sequencing indicated the occurrence of a variable region in
      the hemagglutinin gene.

PMID- 11333917
TI  - Alphaherpesvirus proteins related to herpes simplex virus type 1 ICP0 induce the
      formation of colocalizing, conjugated ubiquitin.
AB  - Herpes simplex virus type 1 immediate early protein ICP0 influences virus
      infection by inducing the degradation of specific cellular proteins via a
      mechanism requiring its RING finger and the ubiquitin-proteasome pathway. Many
      RING finger proteins, by virtue of their RING finger domain, interact with E2
      ubiquitin-conjugating enzymes and act as a component of an E3 ubiquitin ligase.
      We have recently shown that ICP0 induces the accumulation of colocalizing,
      conjugated ubiquitin, suggesting that ICP0 can act as or contribute to an E3
      ubiquitin ligase. In this report we demonstrate that the ICP0-related RING finger
      proteins encoded by other alphaherpesviruses also induce colocalizing, conjugated
      ubiquitin, thereby suggesting that they act by similar biochemical mechanisms.

PMID- 11333918
TI  - Deletion of the cytoplasmic tail of the fusion protein of the paramyxovirus
      simian virus 5 affects fusion pore enlargement.
AB  - The fusion (F) protein of the paramxyovirus simian parainfluenza virus 5 (SV5)
      promotes virus-cell and cell-cell membrane fusion. Previous work had indicated
      that removal of the SV5 F protein cytoplasmic tail (F Tail- or FDelta19) caused a
      block in fusion promotion at the hemifusion stage. Further examination has shown
      that although the F Tail- mutant is severely debilitated in promotion of fusion
      as measured by using two reporter gene assays and is debilitated in the formation
      of syncytia relative to the wild-type F protein, the F Tail- mutant is capable of
      promoting the transfer of small aqueous dyes. These data indicate that F Tail- is
      fully capable of promoting formation of small fusion pores. However, enlargement
      of fusion pores is debilitated, suggesting that either the cytoplasmic tail of
      the F protein plays a direct role in pore expansion or that it interacts with
      other components which control pore growth.

PMID- 11333919
TI  - Active and selective transcytosis of cell-free human immunodeficiency virus
      through a tight polarized monolayer of human endometrial cells.
AB  - We report that both primary and laboratory-adapted infectious human
      immunodeficiency virus type 1 (HIV-1) isolates in a cell-free form are capable of
      transcytosis through a tight and polarized monolayer of human endometrial cells.
      Trancytosis of cell-free HIV occurs in a strain-selective fashion and appears to
      be dependent on interactions between HIV envelope glycoproteins and lectins on
      the apical membrane of the epithelial cells. These findings provide new insights
      into the initial events occurring during heterosexual transmission of the virus.

PMID- 11333920
TI  - Structural analysis of a fiber-pseudotyped adenovirus with ocular tropism
      suggests differential modes of cell receptor interactions.
AB  - Adenovirus (Ad) entry into cells is initiated by the binding of the fiber knob to
      a cell surface receptor. The coxsackie- and adenovirus receptor (CAR) functions
      as the attachment receptor for many, but not all, Ad serotypes. Ad type 37
      (Ad37), a subgroup D virus that causes keratoconjunctivitis in humans, does not
      infect cells via CAR despite demonstrated binding of the Ad37 knob to CAR. We
      have pseudotyped a fiber deletion Ad5 vector with the Ad37 fiber (Ad37f), and
      this vector retains the ocular tropism of Ad37. Here we present a cryo-electron
      microscopy reconstruction of Ad37f that shows the entire Ad37 fiber, including
      the shaft and knob domains. We have previously proposed that Ad37 may not utilize
      CAR for cell entry because of the geometric constraints imposed by a rigid fiber
      (E. Wu, J. Fernandez, S. K. Fleck, D. Von Seggern, S. Huang, and G. R. Nemerow,
      Virology 279:78-89, 2001). Consistent with this hypothesis, our structural
      results show that the Ad37 fiber is straight and rigid. Modeling of the
      interaction between Ad37f and host cell receptors indicates that fiber
      flexibility or rigidity, as well as length, can affect receptor usage and
      cellular tropism.

PMID- 11333921
TI  - Biophysical analysis of natural variants of the multimerization region of Epstein
      Barr virus lytic-switch protein BZLF1.
AB  - BZLF1 plays a key role in the induction of Epstein-Barr virus (EBV) replication.
      On the basis of limited sequence homology and mutagenesis experiments, BZLF1 has
      been described as a member of the bZip family of transcription factors, but this
      prospect has not been rigorously tested to date. Here, we present biophysical
      analysis of the multimerization domain of BZLF1, from three natural variants of
      EBV, and demonstrate for the first time that the region between amino acids 196
      and 227 is sufficient to direct folding as a coiled-coil dimer in vitro.

PMID- 11333922
TI  - The C terminus of brome mosaic virus coat protein controls viral cell-to-cell and
      long-distance movement.
AB  - To investigate the functional domains of the coat protein (CP; 189 amino acids)
      of Brome mosaic virus, a plant RNA virus, 19 alanine-scanning mutants were
      constructed and tested for their infectivity in barley and Nicotiana benthamiana.
      Despite its apparent normal replicative competence and CP production, the C
      terminal mutant F184A produced no virions. Furthermore, virion-forming C-terminal
      mutants P178A and D182A failed to move from cell to cell in both plant species,
      and mutants D181A and V187A showed host-specific movement. These results indicate
      that the C-terminal region of CP plays some important roles in virus movement and
      encapsidation. The specificity of certain mutations for viral movement in two
      different plant species is evidence for the involvement of host-specific factors.

PMID- 11333924
TI  - Residue 627 of PB2 is a determinant of cold sensitivity in RNA replication of
      avian influenza viruses.
AB  - Human influenza A viruses replicate in the upper respiratory tract at a
      temperature of about 33 degrees C, whereas avian viruses replicate in the
      intestinal tract at a temperature close to 41 degrees C. In the present study, we
      analyzed the influence of low temperature (33 degrees C) on RNA replication of
      avian and human viruses in cultured cells. The kinetics of replication of the NP
      segment were similar at 33 and 37 degrees C for the human A/Puerto-Rico/8/34 and
      A/Sydney/5/97 viruses, whereas replication was delayed at 33 degrees C compared
      to 37 degrees C for the avian A/FPV/Rostock/34 and A/Mallard/NY/6750/78 viruses.
      Making use of a genetic system for the in vivo reconstitution of functional
      ribonucleoproteins, we observed that the polymerase complexes derived from avian
      viruses but not human viruses exhibited cold sensitivity in mammalian cells,
      which was determined mostly by residue 627 of PB2. Our results suggest that a
      reduced ability of the polymerase complex of avian viruses to ensure replication
      of the viral genome at 33 degrees C could contribute to their inability to grow
      efficiently in humans.

PMID- 11333923
TI  - Viral and cellular factors that target the promyelocytic leukemia oncogenic
      domains strongly activate a glucocorticoid-responsive promoter.
AB  - Promyelocytic leukemia (PML) oncogenic domains (PODs) accumulate the
      transcriptional cofactor named CREB binding protein (CBP) and have been suggested
      to function as centers of transcription. Transcriptional activation by nuclear
      hormones, such as glucocorticoids, is augmented by the key constituent of PODs,
      the PML protein, and decreased by the POD-associated Tax protein of human T-cell
      leukemia virus type 1 (HTLV-1). This led to the hypothesis that intact PODs might
      play a positive role in the activation of these promoters. We report here that
      transiently expressed E4orf3 protein of adenovirus type 5, immediate-early
      protein 1 of human cytomegalovirus, and the PML-retinoic acid receptor fusion
      protein from leukemia cells each redistribute CBP within the nucleus. However,
      unlike the Tax protein of HTLV-1, these factors did not inhibit a glucocorticoid
      inducible promoter but strongly enhanced its activity. Thus, at least
      glucocorticoid-induced transcription does not depend on POD integrity.

PMID- 11333925
TI  - Integrin alpha(v)beta1 is an adenovirus coreceptor.
AB  - The human embryonic kidney (HEK293) cell line, commonly used for recombinant
      adenovirus (Ad) propagation, does not express the Ad coreceptor alpha(v)beta3 or
      alpha(v)beta5 integrins, yet these cells are efficiently infected by Ad vectors.
      Here we demonstrate that Ad binds to HEK293 cells via the fiber receptor CAR and
      is subsequently internalized via interaction with integrin alpha(v)beta1.
      Function-blocking antibodies directed against alpha(v) or beta1, but not beta3,
      beta5, or alpha5, integrin subunits block Ad infection and viral endocytosis.
      Therefore, alpha(v)beta1 serves as a coreceptor for Ad infection, and the lack of
      beta3 and/or beta5 but the relatively high expression of alpha(v)beta1 integrins
      on certain tumor cell types may explain why these cells are readily transduced by
      Ad vectors.

PMID- 11333926
TI  - Sequences in influenza A virus PB2 protein that determine productive infection
      for an avian influenza virus in mouse and human cell lines.
AB  - Reverse genetics was used to analyze the host range of two avian influenza
      viruses which differ in their ability to replicate in mouse and human cells in
      culture. Engineered viruses carrying sequences encoding amino acids 362 to 581 of
      PB2 from a host range variant productively infect mouse and human cells.

PMID- 11333927
TI  - Nasal-associated lymphoid tissue is a site of long-term virus-specific antibody
      production following respiratory virus infection of mice.
AB  - Nasal immunoglobulin A provides an initial defense against inhaled respiratory
      pathogens. However, it is not known whether the nasal-associated lymphoid tissues
      (NALT) are able to mount an effective long-lasting pathogen-specific immune
      response, nor is it known whether functional differences exist between the
      organized NALT (O-NALT) and the diffuse NALT lining the nasal passages (D-NALT).
      Here we show that although both the O-NALT and the D-NALT are capable of
      producing virus-specific antibody in response to influenza virus infection, the
      frequency of specific antibody-forming cells in the D-NALT is much greater than
      the frequency observed in the O-NALT. Furthermore, we show that the D-NALT but
      not the O-NALT is the site of long-term virus-specific humoral immunity which
      lasts for the life of the animal. These results indicate that the D-NALT is not
      only the major effector site of the NALT but also the site of local long-term
      specific antibody production.

PMID- 11333928
TI  - Immunoglobulin G (IgG) and IgA, but also nonantibody factors, account for in
      vitro neutralization of human immunodeficiency virus (HIV) type 1 primary
      isolates by serum and plasma of HIV-infected patients.
AB  - The factors present in serum and plasma samples of human immunodeficiency virus
      (HIV)-infected patients that are responsible for the neutralization of four HIV
      type 1 (HIV-1) primary isolates in vitro have been analyzed. Purification of
      immunoglobulins (Ig) by affinity chromatography showed that the activities were
      mostly attributable to IgG and less frequently to IgA. For two samples, we have
      shown that the high-level and broad-spectrum inhibitory activity was essentially
      caused by non-Ig factors interfering with the measurement of antibody-specific
      neutralizing activity.

PMID- 11333929
TI  - Determination of essential amino acids involved in the CD4-independent tropism of
      the X4 human immunodeficiency virus type 1 m7NDK isolate: role of potential N
      glycosylations in the C2 and V3 regions of gp120.
AB  - Seven mutations in the C2, V3, and C3 regions of gp120 are implicated in the
      tropism of the first CD4-independent human immunodeficiency virus type 1 isolate,
      m7NDK. Site-directed mutagenesis revealed that three amino acids are essential to
      maintain this tropism, one in the C2 region and two in the V3 loop. Two mutations
      implied N glycosylation modifications.

PMID- 11333930
TI  - Defective interfering RNAs of a satellite virus.
AB  - Panicum mosaic virus (PMV) is a recently molecularly characterized RNA virus with
      the unique feature of supporting the replication of two subviral RNAs in a few
      species of the family Gramineae. The subviral agents include a satellite RNA
      (satRNA) that is devoid of a coding region and the unrelated satellite panicum
      mosaic virus (SPMV) that encodes its own capsid protein. Here we report the
      association of this complex with a new entity in the RNA world, a defective
      interfering RNA (DI) of a satellite virus. The specificity of interactions
      governing this four-component viral system is illustrated by the ability of the
      SPMV DIs to strongly interfere with the accumulation of the parental SPMV. The
      SPMV DIs do not interfere with PMV satRNA, but they do slightly enhance the rate
      of spread and titer of PMV. The SPMV-derived DIs provide an additional avenue by
      which to investigate fundamental biological questions, including the evolution
      and interactions of infectious RNAs.

PMID- 11333932
TI  - Make the most of palaeodata.

PMID- 11333933
TI  - Learning to speak and write.

PMID- 11333931
TI  - Feline immunodeficiency virus cell entry.
AB  - The process of feline immunodeficiency virus (FIV) cell entry was examined using
      assays for virus replication intermediates. FIV subtype B was found to utilize
      the chemokine receptor CXCR4, but not CCR5, as a cellular receptor. Zidovudine
      blocked formation of late viral replication products most effectively, including
      circular DNA genome intermediates. Our findings extend the role of CXCR4 as a
      primary receptor for CD4-independent cell entry by FIV.

PMID- 11333934
TI  - Study says authors are averse to declaring conflicts of interest.

PMID- 11333935
TI  - Bills threaten total US ban on human cloning.

PMID- 11333936
TI  - Pasteur turns to biotech firms in bid to revitalize research.

PMID- 11333937
TI  - Congress hints at brighter outlook for physical science.

PMID- 11333938
TI  - Dispute over digital music muzzles academic.

PMID- 11333941
TI  - Professors facing power cuts in German university reforms.

PMID- 11333942
TI  - Researchers strike back in animal-rights row.

PMID- 11333943
TI  - Fungus fingered as dogwood disappears from forests.

PMID- 11333945
TI  - On the trail of the neutrino.

PMID- 11333946
TI  - The youth team.

PMID- 11333947
TI  - Who will fill the gap by making nucleic synthesizers now?

PMID- 11333948
TI  - Outbreak needs lab tests and clinical diagnosis.

PMID- 11333949
TI  - Fossil hunters in dispute over Ethiopian sites.

PMID- 11333955
TI  - Newton in Japan.

PMID- 11333950
TI  - What is 'dangerous' climate change?

PMID- 11333956
TI  - Here be no dragons.

PMID- 11333957
TI  - Wiping out dirty displays.

PMID- 11333958
TI  - Protein interactions. Unspinning the web.

PMID- 11333959
TI  - Astronomy. A new twist on neutron stars.

PMID- 11333960
TI  - Cell biology. Asymmetry in action.

PMID- 11333961
TI  - Evolutionary biology. Hybrid costs avoided.

PMID- 11333962
TI  - Neurobiology. Dopamine receptors get a boost.

PMID- 11333964
TI  - Earth science. Hard-cored continents.

PMID- 11333965
TI  - Fundamental physics. Resistance of a perfect wire.

PMID- 11333967
TI  - Lethality and centrality in protein networks.

PMID- 11333968
TI  - Cell culture. Progenitor cells from human brain after death.

PMID- 11333969
TI  - Boundary effects. Refraction of a particle beam.

PMID- 11333970
TI  - Protein function. Chaperonin turned insect toxin.

PMID- 11333971
TI  - Hybridization and adaptive mate choice in flycatchers.
AB  - Hybridization in natural populations is strongly selected against when hybrid
      offspring have reduced fitness. Here we show that, paradoxically, pairing with
      another species may offer the best fitness return for an individual, despite
      reduced fitness of hybrid offspring. Two mechanisms reduce the costs to female
      collared flycatchers of pairing with male pied flycatchers. A large proportion of
      young are sired by conspecific male collared flycatchers through extra-pair
      copulations, and there is a bias in favour of male offspring (which, unlike
      females, are fertile) within hybrid pairs. In combination with temporal variation
      in breeding success, these cost-reducing mechanisms yield quantitative
      predictions about when female collared flycatchers should accept a male pied
      flycatcher as a mate; empirical data agree with these predictions. Apparent
      hybridization may thus represent adaptive mate choice under some circumstances.

PMID- 11333972
TI  - Four-terminal resistance of a ballistic quantum wire.
AB  - The electrical resistance of a conductor is intimately related to the relaxation
      of the momentum of charge carriers. In a simple model, the accelerating force
      exerted on electrons by an applied electric field is balanced by a frictional
      force arising from their frequent collisions with obstacles such as impurities,
      grain boundaries or other deviations from a perfect crystalline order. Thus, in
      the absence of any scattering, the electrical resistance should vanish
      altogether. Here, we observe such vanishing four-terminal resistance in a single
      mode ballistic quantum wire. This result contrasts the value of the standard two
      probe resistance measurements of h/2e2 approximately 13 kOmega. The measurements
      are conducted in the highly controlled geometry afforded by epitaxial growth onto
      the cleaved edge of a high-quality GaAs/AlGaAs heterostructure. Two weakly
      invasive voltage probes are attached to the central section of a ballistic
      quantum wire to measure the inherent resistance of this clean one-dimensional
      conductor.

PMID- 11333973
TI  - Superconductivity in the non-oxide perovskite MgCNi3.
AB  - The interplay of magnetic interactions, the dimensionality of the crystal
      structure and electronic correlations in producing superconductivity is one of
      the dominant themes in the study of the electronic properties of complex
      materials. Although magnetic interactions and two-dimensional structures were
      long thought to be detrimental to the formation of a superconducting state, they
      are actually common features of both the high transition-temperature (Tc) copper
      oxides and low-Tc material Sr2RuO4, where they appear to be essential
      contributors to the exotic electronic states of these materials. Here we report
      that the perovskite-structured compound MgCNi3 is superconducting with a critical
      temperature of 8 K. This material is the three-dimensional analogue of the
      LnNi2B2C family of superconductors, which have critical temperatures up to 16 K
      (ref. 2). The itinerant electrons in both families of materials arise from the
      partial filling of the nickel d-states, which generally leads to ferromagnetism
      as is the case in metallic Ni. The high relative proportion of Ni in MgCNi3
      suggests that magnetic interactions are important, and the lower Tc of this three
      dimensional compound-when compared to the LnNi2B2C family-contrasts with
      conventional ideas regarding the origins of superconductivity.

PMID- 11333974
TI  - Atomic-beam alignment of inorganic materials for liquid-crystal displays.
AB  - The technique used to align liquid crystals-rubbing the surface of a substrate on
      which a liquid crystal is subsequently deposited-has been perfected by the
      multibillion-dollar liquid-crystal display industry. However, it is widely
      recognized that a non-contact alignment technique would be highly desirable for
      future generations of large, high-resolution liquid-crystal displays. A number of
      alternative alignment techniques have been reported, but none of these have so
      far been implemented in large-scale manufacturing. Here, we report a non-contact
      alignment process, which uses low-energy ion beams impinging at a glancing angle
      on amorphous inorganic films, such as diamond-like carbon. Using this approach,
      we have produced both laptop and desktop displays in pilot-line manufacturing,
      and found that displays of higher quality and reliability could be made at a
      lower cost than the rubbing technique. The mechanism of alignment is explained by
      adopting a random network model of atomic arrangement in the inorganic films.
      Order is induced by exposure to an ion beam because unfavourably oriented rings
      of atoms are selectively destroyed. The planes of the remaining rings are
      predominantly parallel to the direction of the ion beam.

PMID- 11333975
TI  - Size-dependent control of the binding of biotinylated proteins to streptavidin
      using a polymer shield.
AB  - Many medical and biotechnological processes rely on controlling and manipulating
      the molecular-recognition capabilities of proteins. This can be achieved using
      small molecules capable of competing for protein binding or by changing
      environmental parameters that affect protein structure and hence binding. An
      alternative is provided by stimuli-responsive polymers that change reversibly
      from a water-soluble expanded coil to a water-insoluble collapsed globule upon
      small changes in temperature, pH or light intensity: when attached to proteins in
      the vicinity of their binding sites, they reversibly block and release small
      ligands. Here we show how this approach can be extended to achieve size-selective
      binding of large, macromolecular ligands. We use the thermally responsive polymer
      poly(N,N-diethylacrylamide) (PDEAAm), and attach it to the protein streptavidin
      approximately 20 A from the binding site for biotinylated proteins. Below the
      lower critical solution temperature of PDEAAm, the polymer is in its extended
      state and acts as a 'shield' to block the binding of large biotinylated proteins;
      above this temperature, it collapses and exposes the binding site, thereby
      allowing binding. We find that the degree of shielding depends on both the size
      of the biotinylated protein and the size of PDEAAm, suggesting that 'smart'
      polymer shields could be tailored to achieve a wide range of size-dependent
      ligand discrimination for use in affinity separations, biosensors and diagnostics
      technologies.

PMID- 11333976
TI  - Evolution of Asian monsoons and phased uplift of the Himalaya-Tibetan plateau
      since Late Miocene times.
AB  - The climates of Asia are affected significantly by the extent and height of the
      Himalayan mountains and the Tibetan plateau. Uplift of this region began about 50
      Myr ago, and further significant increases in altitude of the Tibetan plateau are
      thought to have occurred about 10-8 Myr ago, or more recently. However, the
      climatic consequences of this uplift remain unclear. Here we use records of
      aeolian sediments from China and marine sediments from the Indian and North
      Pacific oceans to identify three stages of evolution of Asian climates: first,
      enhanced aridity in the Asian interior and onset of the Indian and east Asian
      monsoons, about 9-8 Myr ago; next, continued intensification of the east Asian
      summer and winter monsoons, together with increased dust transport to the North
      Pacific Ocean, about 3.6-2.6 Myr ago; and last, increased variability and
      possible weakening of the Indian and east Asian summer monsoons and continued
      strengthening of the east Asian winter monsoon since about 2.6 Myr ago. The
      results of a numerical climate-model experiment, using idealized stepwise
      increases of mountain-plateau elevation, support the argument that the stages in
      evolution of Asian monsoons are linked to phases of Himalaya-Tibetan plateau
      uplift and to Northern Hemisphere glaciation.

PMID- 11333977
TI  - Phosphorus limitation of nitrogen fixation by Trichodesmium in the central
      Atlantic Ocean.
AB  - Marine fixation of atmospheric nitrogen is believed to be an important source of
      biologically useful nitrogen to ocean surface waters, stimulating productivity of
      phytoplankton and so influencing the global carbon cycle. The majority of
      nitrogen fixation in tropical waters is carried out by the marine cyanobacterium
      Trichodesmium, which supplies more than half of the new nitrogen used for primary
      production. Although the factors controlling marine nitrogen fixation remain
      poorly understood, it has been thought that nitrogen fixation is limited by iron
      availability in the ocean. This was inferred from the high iron requirement
      estimated for growth of nitrogen fixing organisms and the higher apparent
      densities of Trichodesmium where aeolian iron inputs are plentiful. Here we
      report that nitrogen fixation rates in the central Atlantic appear to be
      independent of both dissolved iron levels in sea water and iron content in
      Trichodesmium colonies. Nitrogen fixation was, instead, highly correlated to the
      phosphorus content of Trichodesmium and was enhanced at higher irradiance.
      Furthermore, our calculations suggest that the structural iron requirement for
      the growth of nitrogen-fixing organisms is much lower than previously calculated.
      Although iron deficiency could still potentially limit growth of nitrogen-fixing
      organisms in regions of low iron availability-for example, in the subtropical
      North Pacific Ocean-our observations suggest that marine nitrogen fixation is not
      solely regulated by iron supply.

PMID- 11333978
TI  - Preservation of ancient and fertile lithospheric mantle beneath the southwestern
      United States.
AB  - Stable continental regions, free from tectonic activity, are generally found only
      within ancient cratons-the centres of continents which formed in the Archaean
      era, 4.0-2.5 Gyr ago. But in the Cordilleran mountain belt of western North
      America some younger (middle Proterozoic) regions have remained stable, whereas
      some older (late Archaean) regions have been tectonically disturbed, suggesting
      that age alone does not determine lithospheric strength and crustal stability.
      Here we report rhenium-osmium isotope and mineral compositions of peridotite
      xenoliths from two regions of the Cordilleran mountain belt. We found that the
      younger, undeformed Colorado plateau is underlain by lithospheric mantle that is
      'depleted' (deficient in minerals extracted by partial melting of the rock),
      whereas the older (Archaean), yet deformed, southern Basin and Range province is
      underlain by 'fertile' lithospheric mantle (not depleted by melt extraction). We
      suggest that the apparent relationship between composition and lithospheric
      strength, inferred from different degrees of crustal deformation, occurs because
      depleted mantle is intrinsically less dense than fertile mantle (due to iron
      having been lost when melt was extracted from the rock). This allows the depleted
      mantle to form a thicker thermal boundary layer between the deep convecting
      mantle and the crust, thus reducing tectonic activity at the surface. The
      inference that not all Archaean crust developed a strong and thick thermal
      boundary layer leads to the possibility that such ancient crust may have been
      overlooked because of its intensive reworking or lost from the geological record
      owing to preferential recycling.

PMID- 11333979
TI  - Consistent patterns and the idiosyncratic effects of biodiversity in marine
      ecosystems.
AB  - Revealing the consequences of species extinctions for ecosystem function has been
      a chief research goal and has been accompanied by enthusiastic debate. Studies
      carried out predominantly in terrestrial grassland and soil ecosystems have
      demonstrated that as the number of species in assembled communities increases, so
      too do certain ecosystem processes, such as productivity, whereas others such as
      decomposition can remain unaffected. Diversity can influence aspects of ecosystem
      function, but questions remain as to how generic the patterns observed are, and
      whether they are the product of diversity, as such, or of the functional roles
      and traits that characterize species in ecological systems. Here we demonstrate
      variable diversity effects for species representative of marine coastal systems
      at both global and regional scales. We provide evidence for an increase in
      complementary resource use as diversity increases and show strong evidence for
      diversity effects in naturally assembled communities at a regional scale. The
      variability among individual species responses is consistent with a positive but
      idiosyncratic pattern of ecosystem function with increased diversity.

PMID- 11333980
TI  - Larval dispersal potential of the tubeworm Riftia pachyptila at deep-sea
      hydrothermal vents.
AB  - Hydrothermal vents are ephemeral because of frequent volcanic and tectonic
      activities associated with crust formation. Although the larvae of hydrothermal
      vent fauna can rapidly colonize new vent sites separated by tens to hundreds of
      kilometres, the mechanisms by which these larvae disperse and recruit are not
      understood. Here we integrate physiological, developmental and hydrodynamic data
      to estimate the dispersal potential of larvae of the giant tubeworm Riftia
      pachyptila. At in situ temperatures and pressures (2 degrees C and 250 atm), we
      estimate that the metabolic lifespan for a larva of R. pachyptila averages 38
      days. In the measured flow regime at a fast-spreading ridge axis (9 degrees 50'
      N; East Pacific Rise), this lifespan results in potential along-ridge dispersal
      distances that rarely exceed 100 km. This limited dispersal results not from the
      physiological performance of the embryos and larvae, but instead from transport
      limitations imposed by periodic reversals in along-ridge flows and sustained
      episodes of across-ridge flow. The lifespan presented for these larvae can now be
      used to predict dispersal under current regimes at other hydrothermal vent sites.

PMID- 11333981
TI  - Foci of orientation plasticity in visual cortex.
AB  - Cortical areas are generally assumed to be uniform in their capacity for adaptive
      changes or plasticity. Here we demonstrate, however, that neurons in the cat
      striate cortex (V1) show pronounced adaptation-induced short-term plasticity of
      orientation tuning primarily at specific foci. V1 neurons are clustered according
      to their orientation preference in iso-orientation domains that converge at
      singularities or pinwheel centres. Although neurons in pinwheel centres have
      similar orientation tuning and responses to those in iso-orientation domains, we
      find that they differ markedly in their capacity for adaptive changes. Adaptation
      with an oriented drifting grating stimulus alters responses of neurons located at
      and near pinwheel centres to a broad range of orientations, causing repulsive
      shifts in orientation preference and changes in response magnitude. In contrast,
      neurons located in iso-orientation domains show minimal changes in their tuning
      properties after adaptation. The anisotropy of adaptation-induced orientation
      plasticity is probably mediated by inhomogeneities in local intracortical
      interactions that are overlaid on the map of orientation preference in V1.

PMID- 11333982
TI  - BDNF controls dopamine D3 receptor expression and triggers behavioural
      sensitization.
AB  - Brain-derived neurotrophic factor (BDNF), like other neurotrophins, is a
      polypeptidic factor initially regarded to be responsible for neuron
      proliferation, differentiation and survival, through its uptake at nerve
      terminals and retrograde transport to the cell body. A more diverse role for BDNF
      has emerged progressively from observations showing that it is also transported
      anterogradely, is released on neuron depolarization, and triggers rapid
      intracellular signals and action potentials in central neurons. Here we report
      that BDNF elicits long-term neuronal adaptations by controlling the
      responsiveness of its target neurons to the important neurotransmitter, dopamine.
      Using lesions and gene-targeted mice lacking BDNF, we show that BDNF from
      dopamine neurons is responsible for inducing normal expression of the dopamine D3
      receptor in nucleus accumbens both during development and in adulthood. BDNF from
      corticostriatal neurons also induces behavioural sensitization, by triggering
      overexpression of the D3 receptor in striatum of hemiparkinsonian rats. Our
      results suggest that BDNF may be an important determinant of pathophysiological
      conditions such as drug addiction, schizophrenia or Parkinson's disease, in which
      D3 receptor expression is abnormal.

PMID- 11333983
TI  - Membrane protein diffusion sets the speed of rod phototransduction.
AB  - Retinal rods signal the activation of a single receptor molecule by a photon. To
      ensure efficient photon capture, rods maintain about 109 copies of rhodopsin
      densely packed into membranous disks. But a high packing density of rhodopsin may
      impede other steps in phototransduction that take place on the disk membrane, by
      restricting the lateral movement of, and hence the rate of encounters between,
      the molecules involved. Although it has been suggested that lateral diffusion of
      proteins on the membrane sets the rate of onset of the photoresponse, it was
      later argued that the subsequent processing of the complexes was the main
      determinant of this rate. The effects of protein density on response shut-off
      have not been reported. Here we show that a roughly 50% reduction in protein
      crowding achieved by the hemizygous knockout of rhodopsin in transgenic mice
      accelerates the rising phases and recoveries of flash responses by about 1.7-fold
      in vivo. Thus, in rods the rates of both response onset and recovery are set by
      the diffusional encounter frequency between proteins on the disk membrane.

PMID- 11333984
TI  - Translational repression determines a neuronal potential in Drosophila asymmetric
      cell division.
AB  - Asymmetric cell division is a fundamental strategy for generating cellular
      diversity during animal development. Daughter cells manifest asymmetry in their
      differential gene expression. Transcriptional regulation of this process has been
      the focus of many studies, whereas cell-type-specific 'translational' regulation
      has been considered to have a more minor role. During sensory organ development
      in Drosophila, Notch signalling directs the asymmetry between neuronal and non
      neuronal lineages, and a zinc-finger transcriptional repressor Tramtrack69
      (TTK69) acts downstream of Notch as a determinant of non-neuronal identity. Here
      we show that repression of TTK69 protein expression in the neuronal lineage
      occurs translationally rather than transcriptionally. This translational
      repression is achieved by a direct interaction between cis-acting sequences in
      the 3' untranslated region of ttk69 messenger RNA and its trans-acting repressor,
      the RNA-binding protein Musashi (MSI). Although msi can act downstream of Notch,
      Notch signalling does not affect MSI expression. Thus, Notch signalling is likely
      to regulate MSI activity rather than its expression. Our results define cell-type
      specific translational control of ttk69 by MSI as a downstream event of Notch
      signalling in asymmetric cell division.

PMID- 11333985
TI  - Exploitation of syndecan-1 shedding by Pseudomonas aeruginosa enhances virulence.
AB  - Cell-surface heparan sulphate proteoglycans (HSPGs) are ubiquitous and abundant
      receptors/co-receptors of extracellular ligands, including many microbes. Their
      role in microbial infections is poorly defined, however, because no cell-surface
      HSPG has been clearly connected to the pathogenesis of a particular microbe. We
      have previously shown that Pseudomonas aeruginosa, through its virulence factor
      LasA, enhances the in vitro shedding of syndecan-1-the predominant cell-surface
      HSPG of epithelia. Here we show that shedding of syndecan-1 is also activated by
      P. aeruginosa in vivo, and that the resulting syndecan-1 ectodomains enhance
      bacterial virulence in newborn mice. Newborn mice deficient in syndecan-1 resist
      P. aeruginosa lung infection but become susceptible when given purified syndecan
      1 ectodomains or heparin, but not when given ectodomain core protein, indicating
      that the ectodomain's heparan sulphate chains are the effectors. In wild-type
      newborn mice, inhibition of syndecan-1 shedding or inactivation of the shed
      ectodomain's heparan sulphate chains prevents lung infection. Our findings
      uncover a pathogenetic mechanism in which a host response to tissue injury
      syndecan-1 shedding-is exploited to enhance microbial virulence apparently by
      modulating host defences.

PMID- 11333986
TI  - Initiation of a G2/M checkpoint after ultraviolet radiation requires p38 kinase.
AB  - Response to genotoxic stress can be considered as a multistage process involving
      initiation of cell-cycle arrest and maintenance of arrest during DNA repair.
      Although maintenance of G2/M checkpoints is known to involve Chk1, Chk2/Rad53 and
      upstream components, the mechanisms involved in its initiation are less well
      defined. Here we report that p38 kinase has a critical role in the initiation of
      a G2 delay after ultraviolet radiation. Inhibition of p38 blocks the rapid
      initiation of this checkpoint in both human and murine cells after ultraviolet
      radiation. In vitro, p38 binds and phosphorylates Cdc25B at serines 309 and 361,
      and Cdc25C at serine 216; phosphorylation of these residues is required for
      binding to 14-3-3 proteins. In vivo, inhibition of p38 prevents both
      phosphorylation of Cdc25B at serine 309 and 14-3-3 binding after ultraviolet
      radiation, and mutation of this site is sufficient to inhibit the checkpoint
      initiation. In contrast, in vivo Cdc25C binding to 14-3-3 is not affected by p38
      inhibition after ultraviolet radiation. We propose that regulation of Cdc25B
      phosphorylation by p38 is a critical event for initiating the G2/M checkpoint
      after ultraviolet radiation.

PMID- 11333987
TI  - Microarrays of cells expressing defined cDNAs.
AB  - Genome and expressed sequence tag projects are rapidly cataloguing and cloning
      the genes of higher organisms, including humans. An emerging challenge is to
      rapidly uncover the functions of genes and to identify gene products with desired
      properties. We have developed a microarray-driven gene expression system for the
      functional analysis of many gene products in parallel. Mammalian cells are
      cultured on a glass slide printed in defined locations with different DNAs. Cells
      growing on the printed areas take up the DNA, creating spots of localized
      transfection within a lawn of non-transfected cells. By printing sets of
      complementary DNAs cloned in expression vectors, we make microarrays whose
      features are clusters of live cells that express a defined cDNA at each location.
      Here we demonstrate two uses for our approach: as an alternative to protein
      microarrays for the identification of drug targets, and as an expression cloning
      system for the discovery of gene products that alter cellular physiology. By
      screening transfected cell microarrays expressing 192 different cDNAs, we
      identified proteins involved in tyrosine kinase signalling, apoptosis and cell
      adhesion, and with distinct subcellular distributions.

PMID- 11333988
TI  - An aminoacyl tRNA synthetase whose sequence fits into neither of the two known
      classes.
AB  - Aminoacyl transfer RNA synthetases catalyse the first step of protein synthesis
      and establish the rules of the genetic code through the aminoacylation of tRNAs.
      There is a distinct synthetase for each of the 20 amino acids and throughout
      evolution these enzymes have been divided into two classes of ten enzymes each.
      These classes are defined by the distinct architectures of their active sites,
      which are associated with specific and universal sequence motifs. Because the
      synthesis of aminoacyl-tRNAs containing each of the twenty amino acids is a
      universally conserved, essential reaction, the absence of a recognizable gene for
      cysteinyl tRNA synthetase in the genomes of Archae such as Methanococcus
      jannaschii and Methanobacterium thermoautotrophicum has been difficult to
      interpret. Here we describe a different cysteinyl-tRNA synthetase from M.
      jannaschii and Deinococcus radiodurans and its characterization in vitro and in
      vivo. This protein lacks the characteristic sequence motifs seen in the more than
      700 known members of the two canonical classes of tRNA synthetase and may be of
      ancient origin. The existence of this protein contrasts with proposals that
      aminoacylation with cysteine in M. jannaschii is an auxiliary function of a
      canonical prolyl-tRNA synthetase.

PMID- 11333990
TI  - Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects
      with impaired glucose tolerance.
AB  - BACKGROUND: Type 2 diabetes mellitus is increasingly common, primarily because of
      increases in the prevalence of a sedentary lifestyle and obesity. Whether type 2
      diabetes can be prevented by interventions that affect the lifestyles of subjects
      at high risk for the disease is not known. METHODS: We randomly assigned 522
      middle-aged, overweight subjects (172 men and 350 women; mean age, 55 years; mean
      body-mass index [weight in kilograms divided by the square of the height in
      meters], 31) with impaired glucose tolerance to either the intervention group or
      the control group. Each subject in the intervention group received individualized
      counseling aimed at reducing weight, total intake of fat, and intake of saturated
      fat and increasing intake of fiber and physical activity. An oral glucose
      tolerance test was performed annually; the diagnosis of diabetes was confirmed by
      a second test. The mean duration of follow-up was 3.2 years. RESULTS: The mean
      (+/-SD) amount of weight lost between base line and the end of year 1 was 4.2+/
      5.1 kg in the intervention group and 0.8+/-3.7 kg in the control group; the net
      loss by the end of year 2 was 3.5+/-5.5 kg in the intervention group and 0.8+/
      4.4 kg in the control group (P<0.001 for both comparisons between the groups).
      The cumulative incidence of diabetes after four years was 11 percent (95 percent
      confidence interval, 6 to 15 percent) in the intervention group and 23 percent
      (95 percent confidence interval, 17 to 29 percent) in the control group. During
      the trial, the risk of diabetes was reduced by 58 percent (P<0.001) in the
      intervention group. The reduction in the incidence of diabetes was directly
      associated with changes in lifestyle. CONCLUSIONS: Type 2 diabetes can be
      prevented by changes in the lifestyles of high-risk subjects.

PMID- 11333991
TI  - Lesser response to angiotensin-converting-enzyme inhibitor therapy in black as
      compared with white patients with left ventricular dysfunction.
AB  - BACKGROUND: Black patients with heart failure have a poorer prognosis than white
      patients, a difference that has not been adequately explained. Whether racial
      differences in the response to drug treatment contribute to differences in
      outcome is unclear. To address this issue, we pooled and analyzed data from the
      Studies of Left Ventricular Dysfunction (SOLVD) prevention and treatment trials,
      two large, randomized trials comparing enalapril with placebo in patients with
      left ventricular dysfunction. METHODS: We used a matched-cohort design in which
      up to four white patients were matched with each black patient according to
      trial, treatment assignment, sex, left ventricular ejection fraction, and age. A
      total of 1196 white patients (580 from the prevention trial and 616 from the
      treatment trial) were matched with 800 black patients (404 from the prevention
      trial and 396 from the treatment trial). The average duration of follow-up was 35
      months in the prevention trial and 33 months in the treatment trial. RESULTS: The
      black patients and the matched white patients had similar demographic and
      clinical characteristics, but the black patients had higher rates of death from
      any cause (12.2 vs. 9.7 per 100 person-years) and of hospitalization for heart
      failure (13.2 vs. 7.7 per 100 person-years). Despite similar doses of drug in the
      two groups, enalapril therapy, as compared with placebo, was associated with a 44
      percent reduction (95 percent confidence interval, 27 to 57 percent) in the risk
      of hospitalization for heart failure among the white patients (P<0.001) but with
      no significant reduction among black patients (P=0.74). At one year, enalapril
      therapy was associated with significant reductions from base line in systolic
      blood pressure (by a mean [+/-SD] of 5.0+/-17.1 mm Hg) and diastolic blood
      pressure (3.6+/-10.6 mm Hg) among the white patients, but not among the black
      patients. No significant change in the risk of death was observed in association
      with enalapril therapy in either group. CONCLUSIONS: Enalapril therapy is
      associated with a significant reduction in the risk of hospitalization for heart
      failure among white patients with left ventricular dysfunction, but not among
      similar black patients. This finding underscores the need for additional research
      on the efficacy of therapies for heart failure in black patients.

PMID- 11333992
TI  - Race and the response to adrenergic blockade with carvedilol in patients with
      chronic heart failure.
AB  - BACKGROUND: The benefits of angiotensin-converting-enzyme inhibitors and beta
      blockers may be smaller in black patients than in patients of other races, but it
      is unknown whether race influences the response to carvedilol in patients with
      chronic heart failure. METHODS: In the U.S. Carvedilol Heart Failure Trials
      Program, 217 black and 877 nonblack patients (in New York Heart Association class
      II, III, or IV and with a left ventricular ejection fraction of no more than
      0.35) were randomly assigned to receive placebo or carvedilol (at doses of 6.25
      to 50 mg twice daily) for up to 15 months. The effects of carvedilol on ejection
      fraction, clinical status, and major clinical events were retrospectively
      compared between black and nonblack patients. RESULTS: As compared with placebo,
      carvedilol lowered the risk of death from any cause or hospitalization for any
      reason by 48 percent in black patients and by 30 percent in nonblack patients.
      Carvedilol reduced the risk of worsening heart failure (heart failure leading to
      death, hospitalization, or a sustained increase in medication) by 54 percent in
      black patients and by 51 percent in nonblack patients. The ratios of the relative
      risks associated with carvedilol for these two outcome variables in black as
      compared with nonblack patients were 0.74 (95 percent confidence interval, 0.42
      to 1.34) and 0.94 (95 percent confidence interval, 0.43 to 2.05), respectively.
      Carvedilol also improved functional class, ejection fraction, and the patients'
      and physicians' global assessments in both the black patients and the nonblack
      patients. For all these measures of outcome and clinical status, carvedilol was
      superior to placebo within each racial cohort (P<0.05 in all analyses), and there
      was no significant interaction between race and treatment (P> 0.05 in all
      analyses). CONCLUSIONS: The benefit of carvedilol was apparent and of similar
      magnitude in both black and nonblack patients with heart failure.

PMID- 11333993
TI  - Intrauterine transmission of cytomegalovirus to infants of women with
      preconceptional immunity.
AB  - BACKGROUND: Preconceptional immunity against cytomegalovirus (CMV) provides only
      partial protection against intrauterine transmission of the virus. Whether
      congenital CMV infection in the offspring of women who are seropositive for CMV
      can occur after maternal reinfection with a different strain of CMV is unknown.
      METHODS: Serum specimens from 46 women with preconceptional immunity against CMV
      that were obtained during the previous pregnancy and the current pregnancy were
      analyzed for antibodies against the strain-specific epitopes of CMV glycoprotein
      H. Virus-neutralizing activity in maternal serum samples was measured against the
      AD169 laboratory strain of CMV and the CMV isolates available from seven infected
      infants. In addition, the nucleotide sequences of the glycoprotein H gene from
      the seven CMV isolates were determined. RESULTS: Eleven of the 16 mothers with
      infected infants (69 percent) had antibodies against the glycoprotein H epitopes
      present on two laboratory strains of CMV, AD169 and Towne. Ten of the 16 mothers
      with infected children (62 percent) acquired new antibody specificities against
      glycoprotein H, as compared with only 4 of the 30 mothers of uninfected infants
      (13 percent, P<0.001). The samples obtained at the time of the current delivery
      from four of the seven mothers contained at least twice as many neutralizing
      antibodies against the CMV isolated from their infants as were present in the
      samples obtained at the previous delivery. The specificity of the newly acquired
      maternal antibodies reflected the amino acid sequence of the glycoprotein H
      epitope of CMV from these four infants. CONCLUSIONS: In women who are
      seropositive for CMV, reinfection with a different strain of CMV can lead to
      intrauterine transmission and symptomatic congenital infection.

PMID- 11333994
TI  - Images in clinical medicine. Waterhouse-Friderichsen syndrome.

PMID- 11333995
TI  - Clinical practice. Prostate-specific-antigen testing for early diagnosis of
      prostate cancer.

PMID- 11333996
TI  - Meningococcal disease.

PMID- 11333998
TI  - Changing habits to delay diabetes.

PMID- 11333999
TI  - Racial profiling in medical research.

PMID- 11334002
TI  - [Recent trends and developments in the military medicine engineering].

PMID- 11334003
TI  - [Scientific problems of medical support of the Air Forces staff].
AB  - The authors consider three leading directions of aeromedical investigations
      oriented at: creation of scientific fundamentals to provide a human factor in
      development of new air to complexes for protection of aviation specialists from
      flight effects and for their labour means humanisation, improvement of
      psychophysiological selection, development of methods and technical means to form
      professionally important qualities and psychophysiological training of air force
      staff, health condition medical control, methods and means of condition
      correction, serviceability restoration and combat-capability increase. The most
      urgent scientific problems are characterized within the given trends. The
      examples of practical effectiveness of the investigations carried out are
      described.

PMID- 11334004
TI  - [Development of preventive and emergency therapy means for poisonous and highly
      toxic substances].
AB  - Threat of accident development at the chemical industry objects, as well as tasks
      of medical support in chemical weapon destruction necessitate improvement of the
      toxicant biological indication methods, creation of protective-decontaminating
      prescriptions to protect open areas of skin, and also development of etiotropic
      and pathogenetic therapy agents for poisonings The Scientific-Research-Test
      Center (Medicobiologic Protection) studies of every of the above trends have
      allowed to create and introduce into table medical support of the RF Armed Forces
      some new indication-means samples, antichemical packets, antidotes and means of
      pathogenetic therapy for convulsive and bronchospastic syndromes, to motivate use
      of pharmacological agents to stop toxic pulmonary edema and cardio-vascular
      failure.

PMID- 11334005
TI  - [Modern means for surgical treatment of focal hepatic lesions].

PMID- 11334006
TI  - [Comparative efficacy of remeron (mirtazapine) and amitriptyline in treatment of
      patients with depression of moderate intensity].

PMID- 11334007
TI  - [The most important results and prospects of the scientific research in the
      protection of Army and Navy Forces against adverse biological factors].

PMID- 11334008
TI  - [Epidemiologic efficacy of vaccine Influvac in the immune prophylaxis of
      influenza in organized groups of workers].

PMID- 11334009
TI  - [The State Scientific Research Testing Institute of Military Medicine of the
      Ministry of Defense of the Russian Federation: history landmarks].

PMID- 11334010
TI  - The spastic paraplegia SPG10 locus: narrowing of critical region and exclusion of
      sodium channel gene SCN8A as a candidate.

PMID- 11334011
TI  - Cytogenetic and molecular study of a jumping translocation in a baby with Dandy
      Walker malformation.

PMID- 11334012
TI  - Clinical and cytogenetic characterisation of a patient with Down syndrome
      resulting from a 21q22.1-->qter duplication.

PMID- 11334013
TI  - Bilateral malformative glaucoma associated with cataract: 36 years of follow-up.

PMID- 11334014
TI  - Evaluation of frequency doubling perimetry in ocular hypertone.

PMID- 11334016
TI  - [Concerning "Toothpicks: be careful!"].

PMID- 11334015
TI  - Latanoprost and the ibopamine test: a year's experience.
AB  - We report here the results obtained in a group of 52 eyes affected by open-angle
      Glaucoma (OAG), whose intraocular pressure (IOP) was inadequately controlled by
      two drugs of different pharmacological categories, into which there was
      introduced Latanoprost, both in place of one of the two drugs and in addition to
      the preceding therapy. The ocular hypotensive effect was good (21.74%). The
      ibopamine provocative test, carried out before the Latanoprost administration,
      and at 3 and 6 months into treatment gave evidence that outflow pathway
      compromission was uninfluenced by the drug.

PMID- 11334017
TI  - The origin of isocortical development.

PMID- 11334019
TI  - Glia-neuronal culture models--do we need to change the paradigms?

PMID- 11334018
TI  - Time-variant processing in V1: from microscopic (single cell) to mesoscopic
      (population) levels.

PMID- 11334020
TI  - Viktor Hamburger at 100: eight decades of neuroembryological research, 1920-
      2000.

PMID- 11334021
TI  - Viktor Hamburger, a tribute.

PMID- 11334022
TI  - Bibliography of Viktor Hamburger (1925--1999).

PMID- 11334024
TI  - Mucosal antigen presentation and the control of tolerance and immunity.

PMID- 11334023
TI  - Antioxidant status and oxidative stress in elite alpine ski racers.
AB  - The goal of this study was to access antioxidant status and markers of oxidative
      damage in elite alpine ski racers during routine training. Subjects included 12
      members of the U.S. Men's Alpine Ski Team attending a 10-day summer training
      camp. Blood draws were collected at rest and after exercise: (a) prior to
      training, (b) following 2 days of dry land training, and (c) after 4 days of on
      snow skiing. Seven measures of antioxidant status were determined using
      colorimetric and HPLC methods (Trolox equivalent antioxidant capacity, uric
      oxidase, alpha-tocopherol, total glutathione, cytosolic glutathione peroxidase,
      and superoxide dismutase). Oxidative stress was assessed using 2 markers of lipid
      oxidation (malondialdehyde and lipid hydroperoxides) and 2 markers of protein
      oxidation (carbonylated total proteins and carbonylated hemoglobin). The results
      of this study suggest that antioxidant status of elite alpine skiers may decline
      over a period of intense training. However, elevations in markers of oxidative
      stress were not evident.

PMID- 11334025
TI  - Ly-6 ligands remain elusive.

PMID- 11334026
TI  - TNF is here to stay--revisited.

PMID- 11334027
TI  - Targeting of vasculature in cancer and other angiogenic diseases.

PMID- 11334028
TI  - Gene diagnosis-introduction of new technology: the tenth international symposium
      of the Hiroshoma cancer seminar, October 2000.

PMID- 11334029
TI  - Alternative strategies other than growth hormone for the treatment of immune
      diseases.

PMID- 11334030
TI  - Inflammatory joint diseases: the province of rheumatologists.

PMID- 11334031
TI  - Immune fate decided by dendritic cell provocateurs.

PMID- 11334032
TI  - Second stroke.

PMID- 11334033
TI  - Dental hygienists are key in spotting domestic violence.

PMID- 11334034
TI  - Welsh assembly scraps prescription charges for under 25s.

PMID- 11334035
TI  - Partnership between NHS and pharmaceutical sector is needed.

PMID- 11334036
TI  - Medical journals are socially responsible about war.

PMID- 11334037
TI  - Is general practice losing its way? The job needs to be split in two.

PMID- 11334038
TI  - Is general practice losing its way? Patients' needs should be put first.

PMID- 11334039
TI  - Study of walk-in centres was flawed.

PMID- 11334040
TI  - Apples and oranges have previously been shown to be remarkably similar.

PMID- 11334041
TI  - [What is it? Right segmental colonic lipomatosis].

PMID- 11334042
TI  - [General radiology: first and ultimate justification for the mastery of imaging
      by radiologists?].

PMID- 11334043
TI  - Back to which basics?

PMID- 11334044
TI  - Vision, mission work wonders.

PMID- 11334045
TI  - Staffing watch.

PMID- 11334046
TI  - Perils of mandatory OT (overtime).

PMID- 11334047
TI  - 1Q[3a] Did the most recent IOM report hit or miss the mark?

PMID- 11334048
TI  - Medication safety issue brief. Using a system-wide approach. Part 4.
AB  - The meat and potatoes of error reduction is in the root cause analysis of
      mistakes and near-misses, and the identification of new, safer ways to carry out
      tasks. This is also the most technical part of patient safety. But hospital
      leaders find that their staffs can learn from mistakes using home-grown expertise
      and wisdom, and that it works best if everyone is willing to open up their daily
      work lives to some well-intentioned scrutiny.

PMID- 11334049
TI  - Profile of U.S. hospitals.

PMID- 11334050
TI  - A challenging agenda.

PMID- 11334051
TI  - Weekly cisplatin/low-dose gemcitabine combination for advanced and recurrent
      cervical carcinoma.
AB  - The aim of this study was to evaluate the activity and safety of the weekly
      cisplatin/low-dose gemcitabine combination in advanced or recurrent cervix
      cancer. Fourteen patients were treated with weekly chemotherapy consisting of
      gemcitabine 100 mg/m2 and cisplatin 33 mg/m2 for a maximum of 18 courses (6
      months). The response rate and survival was evaluated. The mean age of patients
      was 43.4 years, 13 out of 14 had pelvic disease, and most of them received
      previous irradiation. Eleven patients were evaluated for response and all for
      toxicity. The mean number of courses delivered was 9.7. Four patients (36%)
      achieved a partial response and four had stable disease. The most frequent
      toxicity was nausea/vomiting;myelosuppression was mild and uncommon. At a maximum
      follow-up of 15 months the median survival was 6 months. This is an active and
      well-tolerated combination devoid of myelotoxic effects which allows its
      administration without delays.

PMID- 11334052
TI  - The effect of glucocorticosteroid treatment on dentine formation in the Lewis
      rat, a histological study.
AB  - Glucocorticosteroids are widely used in the treatment of chronic illnesses and
      have been reported to cause premature obliteration of the pulp space. During the
      active stages of dentinogenesis, odontoblasts are growth hormone receptor (GHr)
      positive. The aims of this study were to determine if the glucocorticosteroid,
      prednisone, affected the rate of dentine deposition and odontoblast expression of
      GHr in the rat molar. Following subcutaneous injection of 0.05 mg/kg, 1.0 mg/kg
      or 5.0 mg/kg prednisone for 20 days, immature and mature molars from rats aged 3
      and 6 weeks respectively, were examined histologically. Distribution of GHr
      expression was determined immunohistochemically. No morphological differences
      were observed in molars from prednisone treated animals. Prednisone did not
      appear to enhance dentine deposition in immature molars but in mature molars
      significantly increased dentine deposition on the roof of the pulp chamber at a
      dosage of 5.0 mg/kg (p < 0.001). In all immature molars, odontoblasts and pulp
      cells expressed GHr immunoreactivity. In mature molars, odontoblasts and pulpal
      cells from controls did not show GHr immunoreactivity. However, odontoblasts and
      pulp cells were GHr immunoreactive in mature molars from animals treated with
      prednisone.

PMID- 11334053
TI  - Identification of an alternatively spliced mRNA transcript of human betacellulin
      lacking the C-loop of the EGF motif and the transmembrane domain.
AB  - This paper describes the cloning and characterization of a novel cDNA encoding a
      short form of betacellulin (BTC-beta), and reports the expression of this mRNA in
      a variety of human tissues and cell types. BTC-beta is likely the result of
      alternative splicing. This splicing event leads to the generation of an mRNA
      encoding an unusual BTC precursor in which the C-loop of the EGF domain and the
      transmembrane domain are deleted while the remainder of the mature molecule is
      fused in-frame to the C-terminal cytoplasmic tail.

PMID- 11334054
TI  - The 3T3-L1 fibroblast to adipocyte conversion is accompanied by increased
      expression of angiopoietin-1, a ligand for tie2.
AB  - The tie2 receptor tyrosine kinase plays a key role in angiogenesis, and the
      remodeling and maturation of blood vessels. In this study we have used a factor
      dependent cell line (Ba/F3) expressing a chimeric receptor containing the
      extracellular domain of mouse tie2 and the transmembrane and cytoplasmic domain
      of the erythropoietin receptor to identify specific binding activity associated
      with an adipogenic sub-line of 3T3 fibroblasts (3T3-L1). 3T3-L1 fibroblasts are
      capable of undergoing differentiation to adipocytes under specific culture
      conditions. When compared to 3T3-L1 cells, the adipocyte differentiated cultures,
      which contain both pre-adipocytes and adipocytes, exhibited a significantly
      increased ability to support the growth of Ba/F3 cells expressing the chimeric
      receptor. Using probes specific for two recently described ligands for tie2, Ang
      1 and Ang-2, we have shown that mRNA encoding Ang-1 is upregulated when 3T3-L1
      fibroblasts are differentiated to adipocytes. These results suggest that the
      levels of Ang-1 protein and mRNA in 3T3-L1 cells can be regulated by cellular
      differentiation in adipose development.

PMID- 11334055
TI  - Neurotrophin and neurotrophin receptor expression in alveolar macrophages: an
      immunocytochemical study.
AB  - Alveolar macrophages play a crucial role in regulating lung immune responses and
      in maintaining the integrity of the respiratory tract. Neurotrophins (NTs),
      besides to their neurotrophic activities, exhibit physiological effects in the
      immune system. In this study, nerve growth factor (NGF), brain derived
      neurotrophic factor (BDNF), NT-3 and low- (p75) and high affinity (Trks) NT
      receptors were investigated by immunocytochemistry in cytospin centrifuged
      preparations of human alveolar macrophages. Approximately 2.5% alveolar
      macrophages were immunoreactive for NGF, whereas no macrophages displaying
      immunoreactivity for BDNF or NT-3 were observed. A 3.5% macrophages displayed
      immunoreactivity for TrkA-receptor protein, 10% for TrkB-receptor protein (full
      length isoform), and 2% for TrkC-receptor protein. No low-affinity p75 NT and
      TrkB[-] truncated isoform receptor immunoreactive macrophages were found. These
      findings support the hypothesis that NTs and the corresponding receptors may play
      a role in regulating immunological and functional activity of alveolar
      macrophages via paracrine/autocrine mechanisms.

PMID- 11334056
TI  - Cloning of rat betacellulin and characterization of its expression in the
      gastrointestinal tract.
AB  - Betacellulin (BTC) is relatively a more recently discovered member of the EGF
      family of growth factors. As a prelude to its expression and functional studies
      in rat models of gut damage/repair, we have cloned rat BTC and examined its
      expression in the gastrointestinal tract. Rat BTC was found to be nearly
      identical to mouse betacellulin. A single 3 kb mRNA species was detected by
      Northern blotting, and ribonuclease protection analysis showed that its
      expression was ubiquitous but low in abundance throughout the gut. BTC mRNA and
      protein were found expressed in the gastric surface and upper pit epithelium as
      well as in some cells of gastric glands. In the jejunum, BTC mRNA and protein
      were localised to the crypt epithelium and in villous goblet cells. In the colon,
      BTC mRNA and protein were found produced in crypt and surface epithelium as well
      as in goblet cells. Taken together, the wide spread expression in the gut
      epithelium and in mucous cells in particular suggests an important and unique
      role for BTC in the gastrointestinal tract.

PMID- 11334057
TI  - Pharmacokinetic analysis of pegylated megakaryocyte growth and development factor
      in humans.
AB  - Phase I studies with pegylated megakaryocyte growth and development factor (PEG
      rHuMGDF), a c-Mpl ligand that stimulates megakaryopoiesis, have demonstrated that
      PEG-rHuMGDF is biologically active alone and causes a dose-related enhancement of
      platelet recovery when administered after chemotherapy. Here we report the dose
      ranging pharmacokinetics of PEG-rHuMGDF. Pre-injection blood samples were drawn
      daily for pharmacokinetic studies on 43 patients. An ELISA, established using PEG
      rHuMGDF as the standard, was able to quantitate Mpl ligand at concentrations >
      0.02 ng/mL. Over the dose range 0.03 to 5.0 microg/kg/day, subcutaneous
      administration produced linear increases in steady-state serum levels. Maximum
      levels of PEG-rHuMGDF attained after 5.0 microg/kg/day were 5.88 to 10.9 ng/mL.
      After discontinuation of PEG-rHuMGDF, concentrations of Mpl ligand returned to
      baseline within 5 days. The pharmacokinetics were best described by a one
      compartment model with first-order absorption, an absorption delay, and non
      linear clearance over the first 48 hours. The mean terminal half-life was 33.3 +
      16.7 hours, and the average apparent at steady state was 27.7 + 14.0 mL/h/kg;
      both were independent of administered dose. The apparent clearance of PEG-rHuMGDF
      was not predicted by platelet count. Administration of chemotherapy and
      Filgrastim did not alter the pharmacokinetics of PEG-rHuMGDF.

PMID- 11334058
TI  - Etiology of obesity: methodological examination of the set-point theory.

PMID- 11334059
TI  - The A.S.P.E.N. 2000 Research Workshop: Nutrition Support in Transplantation.

PMID- 11334060
TI  - Weight gain and cardiovascular risk after organ transplantation.
AB  - Organ transplantation has become a common and effective approach to the
      management of patients with organ failure. The improvement in long-term survival
      has resulted in the emergence of cardiovascular disease as the primary cause of
      death in renal transplant patients and a significant complication in other organ
      recipients. A number of factors explain this trend, including a high incidence of
      hypertension, posttransplant diabetes, hyperlipidemia, and obesity-risk factors
      that are mediated by direct effects of immunosuppressive medications. Weight gain
      posttransplant affects approximately 50% of patients and represents a significant
      problem because of the potential synergism between obesity and immunosuppressive
      medication-induced effects on cardiovascular disease risk factor development.
      This review discusses the incidence and implications of cardiovascular disease
      risk factors in organ transplant recipients, strategies for clinical management,
      and future research directions.

PMID- 11334061
TI  - Nutrition assessment and support of organ transplant recipients.
AB  - Timely nutrition assessment and intervention in organ transplant recipients may
      improve outcomes surrounding transplantation. A pretransplant nutrition
      assessment should include a variety of parameters including physical assessment,
      history, anthropometric measurements, and laboratory tests. Malnutrition
      compromises posttransplant survival; prolonged waiting times worsen outcomes when
      patients are already malnourished. Severe obesity may decrease graft function and
      survival in kidney transplant recipients. In the pretransplant phase, nutritional
      goals include optimization of nutritional status and treatment of nutrition
      related symptoms induced by organ failure. Enteral tube feeding is indicated for
      patients with functional gastrointestinal tracts who are not eating adequately.
      Parenteral nutrition is rarely needed pretransplant except in cases of intestinal
      failure. When determining pretransplant nutrient requirements, nutritional
      status, weight, age, gender, metabolic state, stage and type of organ failure,
      malabsorption, induced losses, goals, and comorbid conditions must be considered.
      During the acute posttransplant phase, adequate nutrition is required to help
      prevent infection, promote wound healing, support metabolic demands, replenish
      lost stores, and perhaps mediate the immune response. Nutrient recommendations
      reflect posttransplant metabolic changes. The appropriateness of posttransplant
      nutrition support depends on the prevalence of malnutrition among patients with a
      specific type of organ failure and the benefits when nutrition support is given.
      Organ transplantation complications including rejection, infection, wound
      healing, renal insufficiency, hyperglycemia, and surgical complications require
      specific nutritional requirements and therapies. Many potential applications of
      nutrition in the pre- and posttransplant phases exist and require further study.

PMID- 11334062
TI  - Drug-nutrient interactions in transplant recipients.
AB  - Drug-nutrient interaction refers to an alteration of kinetics or dynamics of a
      drug or a nutritional element, or a compromise in nutritional status as a result
      of the addition of a drug. The potentials for drug-nutrient interaction increase
      with the number of drugs taken by the patient. Organ transplant recipients are
      therefore at high risk for drug-nutrient interactions because multiple
      medications are used to manage graft rejection, opportunistic infections, and
      other associated complications. Unrecognized or unmanaged drug-nutrient
      interactions in this patient population can have an adverse impact on their
      outcomes. This paper reviews the importance of recognizing drug-nutrient
      interaction when using cyclosporine-based regimens.

PMID- 11334064
TI  - Influence of tacrolimus and prednisone on serum lipids after liver
      transplantation.
AB  - BACKGROUND: Hyperlipidemia after orthotopic liver transplant is thought to be the
      result of the immunosuppression therapy given postoperatively. The purpose of
      this study was to evaluate serum lipid levels pretransplant, 4 months, and 12
      months posttransplant. METHODS: A retrospective chart review of 50 patients after
      liver transplantation was completed. Pretransplant serum lipid levels
      (triglyceride, cholesterol, and high-density lipoprotein [HDL]) were compared
      with values at 4 months and 12 months posttransplantation. Pretransplant serum
      lipid levels were compared using one factor analysis of variance (ANOVA) model.
      Values between the viral, alcohol, and cholestatic groups were compared using two
      factor ANOVA model. RESULTS: Of the 50 patients (22 females, 28 males) with a
      mean age of 52 years (range, 16 to 69 years), all 50 had completed their 12-month
      follow-up at the time of this study. The etiology of liver disease included:
      viral hepatitis (21), alcohol (8), primary biliary cirrhosis and sclerosing
      cholangitis (7), and others (14). The protocol for immunosuppression included
      tacrolimus and prednisone. Mean serum triglyceride levels included: 134 mg/dL
      pretransplant, 155 mg/dL at 4 months, and 169 mg/dL at 12 months posttransplant
      (p = .117). Mean total serum cholesterol levels included: 174 mg/dL
      pretransplant, 165 mg/dL at 4 months, and 163 mg/dL at 12 months posttransplant
      (p = .654). Mean HDL levels included: 39 mg/dL pretransplant, 45 mg/dL at 4
      months and 44 mg/dL at 12 months posttransplant (p = .032). There was not a
      significant difference in serum lipids between the different categories of liver
      diseases. CONCLUSIONS: Although a significant positive effect was observed with
      HDL, the present data show that total serum cholesterol and triglyceride did not
      change significantly over time after orthotopic transplantation. This is most
      likely related to the type of immunosuppressive therapy given posthepatic
      transplantation.

PMID- 11334063
TI  - Protective role of the L-arginine-nitric oxide synthase pathway on preservation
      injury after rat liver transplantation.
AB  - BACKGROUND: A major problem complicating liver transplantation is the
      preservation injury that results from cold storage and subsequent
      ischemia/reperfusion injury after organ revascularization. The L-arginine-nitric
      oxide (NO) pathway has been recognized to play critical roles during infection,
      inflammation, organ injury, and transplant rejection. Recent data indicates that
      NO synthesis has beneficial effects in several models of liver injury. The
      purpose of this study is to examine the role of the L-arginine-NO pathway on
      preservation injury in an experimental model of rat liver transplantation.
      METHODS: Orthotopic liver transplantation was performed in syngeneic (LEW to LEW)
      rats. Liver preservation injury was determined by measuring serum liver function
      tests 6 to 48 hours after transplantation. In some experiments, rats received L
      arginine supplementation 0 to 24 hours after transplantation. In other
      experiments, NO synthase inhibitors (L-NAME or L-NIL) were injected at the time
      of isograft revascularization. RESULTS: L-Arginine supplementation decreased
      hepatic transaminase levels at all time points examined (6-48 hours). L-Arginine
      produced a significant improvement in liver preservation injury by 12 hours after
      reperfusion. The NO synthase inhibitor L-NAME caused a significant increase in
      liver injury 24 hours after injection. The inducible NO synthase (iNOS)-specific
      inhibitor L-NIL had no significant effect on liver injury. CONCLUSIONS: The
      results show that L-arginine supplementation and NO synthesis improve hepatic
      injury and have a protective role in the transplanted liver graft. The protective
      effect may be mediated by low-level cNOS-derived NO.

PMID- 11334065
TI  - A comparison of renal phosphorus regulation in thermally injured and multiple
      trauma patients receiving specialized nutrition support.
AB  - To compare phosphorus intake and renal phosphorus regulation between thermally
      injured patients and multiple trauma patients, 40 consecutive critically ill
      patients, 20 with thermal injury and 20 with multiple trauma, who required
      enteral tube feeding were evaluated. Phosphorus intakes were recorded for 14 days
      from the initiation of tube feeding which was started 1 to 3 days postinjury.
      Serum for determination of phosphorus concentrations was collected at days 1, 3,
      7, and 14 of the study period. A 24-hour urine collection was obtained during the
      first and second weeks of nutrition support for urinary phosphorus excretion,
      fractional excretion of phosphorus, renal threshold phosphate concentration, and
      phosphorus clearance. Average total daily phosphorus intake during the 14-day
      study for thermally injured patients and multiple trauma patients was 0.99+/-0.26
      mmol/kg/d vs 0.58+/-0.21 mmol/kg/d, respectively, p < .001. Serum phosphorus
      concentration on the third day of observation was significantly lower in the
      thermally injured group than those with multiple trauma (1.9+/-0.8 mg/dL vs 3.0+/
      0.8 mg/dL, p < or = .01). A trend toward hypophosphatemia in the thermally
      injured group persisted by the seventh day of feeding (2.7+/-1.2 mg/dL vs 3.3+/
      0.6 mg/dL, p < or = .04). Differences in urinary phosphorus excretion was not
      statistically significant between the thermally injured and multiple trauma
      groups (271+/-213 mg/d vs 171+/-181 mg/d for week 1, and 320+/-289 mg/d vs 258+/
      184 mg/d for week 2, respectively). Urinary phosphorus clearance, fractional
      excretion of phosphorus, or renal threshold phosphate concentrations were also
      not significantly different between thermally injured and multiple trauma
      patients. During nutrition support, serum phosphorus concentrations are lower in
      thermally injured patients compared with multiple trauma patients despite
      receiving a significantly greater intake of phosphorus. Renal phosphorus
      regulation does not significantly contribute to the profound hypophosphatemia
      observed in thermally injured patients when compared with multiple trauma
      patients during nutrition support.

PMID- 11334066
TI  - Efficacy of erythromycin for postpyloric placement of feeding tubes in critically
      ill children: a randomized, double-blind, placebo controlled study.
AB  - BACKGROUND: Erythromycin enhances gastric emptying and has been suggested to
      facilitate nasoenteric feeding tube placement in adults. Our primary objective
      was to evaluate the effect of erythromycin on the transpyloric passage of feeding
      tubes in critically ill children, and second, to evaluate the effect of
      erythromycin on the distal migration of duodenal feeding tubes. METHODS: Seventy
      four children were randomly assigned to receive erythromycin lactobionate (10
      mg/kg) IV or equal volume of saline placebo 60 minutes before passage of a
      flexible weighted tip feeding tube. Abdominal radiographs were obtained 4 hours
      later to assess tube placement. If the tube was proximal to the third part of the
      duodenum, two additional doses of erythromycin/placebo were administered 6 hours
      apart. Those receiving additional doses had repeat radiographs 14 to 18 hours
      after tube placement. RESULTS: The number of postpyloric feeding tubes was
      similar in the erythromycin and placebo treated groups 4 hours after tube
      insertion (23/37 vs 27/37, p = .5). Of those with prepyloric tubes at 4 hours,
      none in the erythromycin group and 3 in the placebo group had the tube migrate to
      the postpyloric position by 14 to 18 hours (p < .05). Of those with postpyloric
      tubes proximal to the third part of the duodenum at 4 hours, additional doses of
      erythromycin did not cause more tubes to advance further into the intestine than
      did placebo (p = .6). CONCLUSIONS: Erythromycin does not facilitate transpyloric
      passage of feeding tubes in critically ill children. The distal migration of
      duodenal tubes further into the small bowel is also not enhanced by erythromycin.

PMID- 11334067
TI  - Comments on "Small bowel segment reversal induces intestinal hyperplasia but
      reduces whole-body growth in massive bowel resected rats".

PMID- 11334068
TI  - Comments on "Comparison of gastrointestinal tolerance feeding proctocols in
      critically ill patients: a prospective, randomized controlled clinical trial".

PMID- 11334069
TI  - FMD: chief scientist expresses 'cautious optimism' that the controls are working.

PMID- 11334070
TI  - Foot-and-mouth disease makes an impact at BSAVA congress.

PMID- 11334071
TI  - Kidney transplants in cats: where to next?

PMID- 11334072
TI  - Correlation between the clinical course of granulomatous meningoencephalomyelitis
      in dogs and the extent of mast cell infiltration.
AB  - The data from 20 dogs with histopathologically confirmed granulomatous
      meningoencephalomyelitis were reviewed in an attempt to identify clinical signs
      and morphological and cellular parameters, particularly the infiltration of mast
      cells, which might be associated with the clinical course of the disease.
      Thirteen of the dogs had the acute form of the disease and seven had the chronic
      form. Young to middle-aged, small breed female dogs were over-represented.
      Central vestibular signs were observed in six of the dogs with the acute disease.
      Analyses of cerebrospinal fluid revealed moderate to severe pleocytosis and high
      protein concentrations in all cases. Histopathological investigations revealed
      disseminated perivascular cuffs, large confluent granulomata, tissue necrosis,
      infiltration with neutrophils and a large number of mitotic cells in the dogs
      with either of the clinical forms of the disease. Tryptase-positive mast cells
      were observed in all the cases, but there were significantly larger numbers in
      the dogs with the acute form.

PMID- 11334073
TI  - Protection of pigs against challenge with virulent Streptococcus suis serotype 2
      strains by a muramidase-released protein and extracellular factor vaccine.
AB  - The efficacy of a muramidase-released protein (MRP) and extracellular factor (EF)
      vaccine in preventing infection and disease in pigs challenged either with a
      homologous or a heterologous Streptococcus suis serotype 2 strain (MRP+EF+) was
      compared with the efficacy of a vaccine containing formalin-killed bacterin of S.
      suis serotype 2 (MRP+EF+). The enhancement of the immune response by different
      adjuvants (a water-in-oil emulsion [WO] and an aluminium hydroxide-based adjuvant
      [AH]) and their side effects were also studied. The MRP and EF were purified by
      affinity chromatography. Pigs were vaccinated twice at three weeks and six weeks
      of age and challenged intravenously with virulent S. suis serotype 2 strains
      (MRP+EF+) at eight weeks of age. At challenge, the pigs vaccinated with MRP+EF/WO
      had high anti-MRP and anti-EF titres and were protected as effectively as pigs
      vaccinated with WO-formulated vaccines with bacterin. Eight of the nine pigs
      survived the challenge and almost no clinical signs of disease were observed. The
      titres obtained with the MRP+EF/AH vaccine were low and only two of the five pigs
      were protected. Pigs vaccinated with either MRP or EF were less well protected;
      three of the four pigs died after challenge but the clinical signs of disease
      were significantly less severe than those observed in the placebo-vaccinated
      pigs. The protective capacity of the bacterin/AH vaccine was very low, and the
      mortality among these pigs was as high as in the placebo-vaccinated pigs (80 per
      cent). Postmortem histological examination revealed meningitis, polyserositis and
      arthritis in the clinically affected pigs. The results demonstrate that a subunit
      vaccine containing both MRP and EF, formulated with the WO adjuvant, protected
      pigs against challenge with virulent S. suis type 2 strains.

PMID- 11334074
TI  - Prevention and treatment of Encephalitozoon cuniculi infection in rabbits with
      fenbendazole.
AB  - The efficacy of fenbendazole for preventing an experimental infection of
      Encephalitozoon cuniculi and for eliminating the spores from the central nervous
      system of naturally infected rabbits was investigated. Fenbendazole (20 mg/kg
      bodyweight daily) was administered from seven days before until two or 21 days
      after rabbits had been infected orally with 10(6) spores of E. cuniculi. Both
      regimens were effective in preventing the establishment of the parasites, as
      demonstrated by negative parasitic-specific serology and by the failure to
      isolate the parasite from brain tissue. In naturally infected, seropositive
      rabbits, parasites were successfully isolated from seven of nine untreated
      animals, but not from the brain tissue of eight animals treated with fenbendazole
      medicated pellets for four weeks.

PMID- 11334075
TI  - Equine Borna disease in Japan.

PMID- 11334076
TI  - Dual infection with PCV-2 and porcine epidemic diarrhoea virus in neonatal
      piglets.

PMID- 11334078
TI  - Supervision of slaughter.

PMID- 11334077
TI  - Morphometric evaluation of the small intestines and caeca of pheasants infected
      with Hexamita and Trichomonas species.

PMID- 11334079
TI  - Diagnosis of the first two outbreaks of FMD in Ireland.

PMID- 11334080
TI  - TVI provision for FMD control.

PMID- 11334081
TI  - Breeding difficulties.

PMID- 11334082
TI  - Breeding difficulties.

PMID- 11334084
TI  - Congenital stationary night blindness in briards in the UK.

PMID- 11334085
TI  - Glaucoma in the Newfoundland dog.

PMID- 11334086
TI  - VN training scheme.

PMID- 11334087
TI  - Lack of reduction in hospitalizations and emergency department visits for
      varicella in the first 2 years post-vaccine licensure.
AB  - OBJECTIVES: To describe and compare the incidence and spectrum of complications
      of varicella pre-vaccine and post-vaccine licensure. METHODS: We performed a
      retrospective chart review of children under age 21 years either treated in the
      emergency department (ED) or admitted to the hospital with varicella at
      Children's Hospital, Boston, from January to December 1994 (pre-licensure) and
      from January 1996 to December 1997 (post-licensure). RESULTS: We identified 937
      children who made a visit to the ED for varicella and 270 children hospitalized
      for varicella during the 3-year study period. The ratio of varicella-related
      visits to the ED to total visits (0.67%) did not vary significantly from the post
      vaccine ratio (0.60%). The most common reasons for a visit were cellulitis in
      immunocompetent patients and treatment with varicella zoster immune globulin
      (VZIG) in children with immunosuppression. Similarly, the ratio of varicella
      related hospitalizations to total hospitalizations did not vary in the pre
      vaccine (0.53%) and post-vaccine (0.47%) eras. The most common complications in
      hospitalized patients were cellulitis in previously healthy children (37%) and
      uncomplicated varicella in immunocompromised patients (36%). The distribution of
      diagnoses in the ED and complications among hospitalized children did not differ
      significantly in the pre-vaccine and post-vaccine eras. CONCLUSIONS: Despite
      licensure of the varicella vaccine, varicella-related hospitalizations and ED
      visits have not changed significantly. Further efforts are needed to increase
      utilization of the varicella vaccine.

PMID- 11334088
TI  - Bupropion overdose in an adolescent.
AB  - Bupropion is a relatively new monocyclic antidepressant whose mechanism of action
      remains unknown. In addition to its use as an antidepressant, it has also been
      suggested to be effective in children with attention deficit hyperactive disorder
      and more recently as an aid in the cessation of cigarette smoking. The latter
      indication has resulted in an increase in its use and therefore an increased
      availability in households. To date, reports of overdoses in pediatric patients
      are limited. We report a 14-year-old boy who ingested 1.5 to 3 g of bupropion in
      a suicide attempt. Previous reports of bupropion ingestions and its management
      are discussed.

PMID- 11334089
TI  - An unusual presentation of shock in a previously healthy child.
AB  - A previously healthy, 7-year-old African-American male presented to the emergency
      department with a high fever and signs of compensated shock. With this case
      presentation, we review the clinical evaluation of a child in shock and discuss
      the importance of early recognition and treatment. Additionally, the varied
      etiologies of shock in a previously healthy individual are discussed.

PMID- 11334090
TI  - Baclofen overdose in two siblings.
AB  - Baclofen is a muscle relaxant used in both adults and children with neuromuscular
      disorders to control spasticity. In children, relatively few cases of overdose
      have been previously reported. We report two cases of baclofen overdose occurring
      in two siblings. One sibling with cerebral palsy was being treated with baclofen
      at the time of overdose. Both cases presented with severe respiratory depression
      requiring mechanical ventilation. Serum baclofen concentrations from both
      children were significantly elevated. We also review the published literature on
      baclofen overdose in children and adolescents. These cases emphasize the
      importance of warning parents about the potential toxicity of baclofen when
      prescribing the drug to a family member.

PMID- 11334091
TI  - Vaginal laceration and perforation resulting from first coitus.
AB  - Vaginal laceration resulting from coitus is not uncommon and is well described.
      Perforation of the vagina during coitus is a very rare occurrence, and there is
      scant literature reporting it. This is a case of a 14-year-old female who
      suffered both laceration and perforation of the vagina as a result of her first
      coitus, which was consensual. The characteristics of vaginal laceration and
      perforation, presentation, treatment, complications, as well as predisposing
      factors, are discussed.

PMID- 11334092
TI  - Management of acute pain and anxiety in children undergoing procedures in the
      emergency department.

PMID- 11334093
TI  - When to start and when to stop.

PMID- 11334094
TI  - Transillumination of the palm for venipuncture in infants.
AB  - AIM: To assess the efficacy of transillumination of the palm of the hand in
      establishing venous access in small infants. METHODS: One hundred infants aged 2
      to 36 months were considered for venipuncture under transillumination following
      failure to find an accessible vein or a failed venipuncture attempt. RESULTS: In
      40 of the 100 infants, a vein was visible with transillumination. In 22 of these
      children, previous attempts to achieve a venous line failed (mean number of
      failed venipunctures 2.11 +/- 0.6) and in 18 infants, no vein could be
      identified. Using transillumination, venous access was established with just one
      venipuncture in 39 of the 40 patients. CONCLUSIONS: Transillumination of the palm
      can aid in establishing venous access in infants. This can be easily carried out
      using a common otoscope.

PMID- 11334095
TI  - Pediatric emergency medicine: legal briefs.

PMID- 11334096
TI  - Facial injury with drooling.

PMID- 11334097
TI  - The effects of core and peripheral warming methods on temperature and physiologic
      variables in injured children.
AB  - INTRODUCTION: Injured children are at risk for thermoregulatory compromise, where
      temperature maintenance mechanisms are overwhelmed by severe injury,
      environmental exposure, and resuscitation measures. Adequate thermoregulation can
      be maintained, and heat loss can be prevented, by core (administration of warmed
      intravenous fluid) and peripheral (application of convective air warming)
      methods. It is not known which warming method is better to maintain
      thermoregulation and prevent heat loss in injured children during their trauma
      resuscitations. The purpose of this feasibility study was to compare the effects
      of core and peripheral warming measures on body temperature and physiologic
      changes in a small sample of injured children during their initial emergency
      department (ED) treatment. METHODS: A prospective, randomized experimental design
      was used. Eight injured children aged 3 to 14 years (mean = 6.87, SD = 3.44 )
      treated in the ED of Children's Hospital of Pittsburgh were enrolled. Physiologic
      responses (eg, heart rate, blood pressure, respiratory rate, arterial oxygen
      saturation, core, peripheral temperatures) and level of consciousness were
      continuously measured and recorded every 5 minutes to detect early
      thermoregulatory compromise and to determine the child's response to warming.
      Data were collected throughout the resuscitation period, including transport to
      CT scan, the inpatient nursing unit, intensive care unit, operating room or
      discharge to home. Core warming was accomplished with the Hotline Fluid Warmer
      (Sims Level 1, Inc., Rockland, MA), and peripheral warming was accomplished with
      the Snuggle Warm Convective Warming System (Sins Level 1, Inc., Rockland, MA).
      Data were analyzed using descriptive and inferential statistics. RESULTS: There
      were no statistically significant differences between the two groups on age (t = 
      0.485, P = 0.645); weight (t = -0.005, P = 0.996); amount of prehospital
      intravenous (IV) fluid (t = 0314, P = 0.766); temperature on ED arrival (t =
      0.287, P = 0.784); total amount of infused IV fluid (t = -0.21, P = 0.8); and
      length of time from ED admission to hospital admission (t = -0.613, P = 0.56).
      There were no statistically significant differences between the two groups on RTS
      (t = -0.516, P = 0.633). When comparing the mean differences in temperature upon
      hospital admission, no statistically significant differences were found (t = 
      1.572, P = 0.167). There were no statistically significant differences between
      the two groups in tympanic [F(15) = 0.71, P = 0.44] and skin [F(15) = 0.06, P =
      0.81] temperature measurements over time. CONCLUSION: Core and peripheral warming
      methods appeared to e effective in preventing heat loss in this stable patient
      population. A reasonable next step would be to continue this trial in a larger
      sample of patients who are at greater risk for heat loss and subsequent
      hypothermia and to use a control group.

PMID- 11334098
TI  - Iatrogenic metoclopramide toxicity in an infant presenting to a pediatric
      emergency department.

PMID- 11334099
TI  - Management of febrile infants and children by pediatric emergency medicine and
      emergency medicine: comparison with practice guidelines.
AB  - OBJECTIVES: Management of febrile infants and children remains controversial
      despite the 1993 publication in Pediatrics and Annals of Emergency Medicine of
      practice guidelines. Our aim was to determine the management of febrile infants
      and children by pediatric emergency medicine (PEM) fellowship directors and
      emergency medicine (EM) residency directors and compare their approach with the
      published practice guidelines. METHODS: Four case scenarios were sent to 64 PEM
      directors and 100 EM directors in the United States and Canada, describing four
      febrile, nontoxic infants and children aged 25 days (case 1), 7 weeks (case 2), 5
      months (case 3), and 22 months (case 4). Respondents were asked to select which
      laboratory tests and radiographs they would obtain and to decide on treatment and
      disposition for each hypothetical case. RESULTS: Ninety-two percent (53/64) of
      PEM directors and 64% (64/100) of EM directors responded (overall response rate
      74%). Compliance with the guidelines (PEM/EM) was 54%/16% for case 1, 31%/6% for
      case 2, 35%/19% for case 3, and 20%/11% for case 4. Only 11% of PEM and 2% of EM
      directors followed the guidelines for all four cases. Overall, directors
      performed fewer laboratory tests, ordered more chest radiographs and treated
      fewer patients with antibiotics than the expert panel suggested. EM directors
      ordered more chest radiographs (cases 1-4) and admitted more patients (case 2)
      than PEM directors. CONCLUSIONS: There is poor compliance with published practice
      guidelines in the management of febrile infants and children among PEM and EM
      directors.

PMID- 11334100
TI  - Clinical significance of scalp abnormalities in asymptomatic head-injured
      infants.
AB  - OBJECTIVES: 1) To identify clinical features indicating a high risk of skull
      fracture (SF) and associated intracranial injury (ICI) in asymptomatic head
      injured infants. 2) To develop a clinical decision rule to determine which
      asymptomatic head-injured infants require head imaging. METHODS: We performed a
      prospective cohort study of all asymptomatic head-injured infants 0-24 months of
      age presenting to the emergency department of an urban children's hospital.
      Infants were considered asymptomatic if they had no clinical signs of brain
      injury, or of basilar or depressed SF. Among subjects who had head imaging, we
      assessed the utility of age, scalp hematoma size, and scalp hematoma location for
      predicting SF and ICI. RESULTS: Of 422 study patients, 45 (11 %) were diagnosed
      with SF and 13 (3%) with ICI. In the 172 subjects who had head imaging, there was
      a stepwise relationship between hematoma size and likelihood of SF. Parietal and
      temporal hematomas were highly associated with SF; frontal hematomas were not.
      There was a trend toward higher rates of SF in younger patients. Both large scalp
      hematoma and parietal hematoma were associated with ICI. Using these data, we
      developed a clinical decision rule to determine which asymptomatic infants need
      head imaging. In our study population, this rule has a sensitivity of 0.98 and
      specificity of 0.49 for SF, and it detects all 13 cases of ICI. The clinical rule
      calls for imaging in 146/422 (35%) study subjects. CONCLUSIONS: Among
      asymptomatic head-injured infants, the risk of SF and associated ICI is
      correlated with scalp hematoma size, hematoma location, and weakly with patient
      age. We propose a clinical decision rule that could identify most cases of SF and
      ICI while not requiring head imaging for most patients. This decision rule should
      be validated in other study populations.

PMID- 11334101
TI  - Foster parents of medically fragile children can improve their BLS scores:
      results of a demonstration project.
AB  - OBJECTIVES: 1) To assess performance and comfort level with cardiopulmonary
      resuscitation (CPR), foreign body removal (FBR), and seizure management in foster
      parents of medically fragile children; 2) To determine if the parents'
      performance and comfort levels increase with an individual teaching session with
      a medical professional to review CPR and FBR. METHODS: In this single cohort
      pilot study, 18 foster parents of medically fragile children were asked to rate
      their comfort level with pediatric CPR and FBR on a 5-point scale (1 = very
      uncomfortable, 5 = very comfortable). They then underwent five mock code
      scenarios and were evaluated using a 5-point scale (1 = poor performance, 5 =
      outstanding performance). A 6-month follow-up evaluation using similar scenarios
      was conducted. RESULTS: At visit 1, the percentage of parents demonstrating
      adequate performance of CPR, FBR, and seizure management was: 1) CPR: infant
      (78%); child (78%); 2) Foreign body removal: age <1 year (17%); age >1 year
      (65%); 3) Seizures (94%). At visit 2, performance improved in all areas,
      especially FBR, where the percentage of parents demonstrating adequate
      performance increased to 71% for children <1 year and 82% for children >1 year.
      As measured by the 5-point scales, CPR and FBR performance and parent comfort
      level with CPR improved significantly (Wilcoxon signed-ranks test, P < 0.004),
      but parent comfort level with FBR did not (P = 0.12). CONCLUSIONS: Based on this
      pilot study, foster parents of medically fragile children benefit from an
      individual teaching session by a medical professional. CPR instruction for this
      group of foster parents should include adequate review and assessment of foreign
      body removal procedures.

PMID- 11334102
TI  - Effectiveness of a pediatric trauma team protocol.
AB  - OBJECTIVE: To determine the effectiveness of a pediatric trauma triage system and
      resource allocation for emergency medicine and trauma services. TRAUMA SYSTEM:
      Two-tier trauma team activation system that triages patients into Level 1 and
      Level 2 trauma alert categories based on information provided by pre-hospital
      providers to pediatric emergency physicians at an American College of Surgeons'
      Level 1 pediatric trauma center in Columbus, Ohio. METHODS: Using the hospital
      trauma registry database and patient medical records, a retrospective chart
      review was conducted on all (n = 542) admitted pediatric trauma patients from
      January 1995 through December 1996. RESULTS: Level 1 patients had a higher median
      injury severity score and shorter emergency department (ED) length of stay time
      than Level 2 patients. Level 1 patients were more likely to be admitted to the
      pediatric intensive care unit and remain for more than 24 hours when compared to
      Level 2 patients. In addition, Level 1 patients were more likely to have
      procedures performed (eg, intubation, tube thoracostomy, thoracotomy, diagnostic
      peritoneal lavage) than Level 2 patients. The mortality rate was significantly
      higher for Level 1 patients and all ED deaths had been triaged to the Level 1
      category. CONCLUSIONS: This pediatric trauma triage system effectively predicts
      which patients will be more likely to have serious injury. By using a two-tier
      system, select patients may be managed by a smaller trauma team, thus improving
      staff utilization and possibly reducing costs while ensuring favorable outcomes.

PMID- 11334103
TI  - A nanosecond molecular dynamics study of antiparallel d(G)7 quadruplex
      structures: effect of the coordinated cations.
AB  - Nanosecond scale molecular dynamics simulations have been performed on
      antiparallel Greek key type d(G7) quadruplex structures with different
      coordinated ions, namely Na+ and K+ ion, water and Na+ counter ions, using the
      AMBER force field and Particle Mesh Ewald technique for electrostatic
      interactions. Antiparallel structures are stable during the simulation, with root
      mean square deviation values of approximately 1.5 A from the initial structures.
      Hydrogen bonding patterns within the G-tetrads depend on the nature of the
      coordinated ion, with the G-tetrad undergoing local structural variation to
      accommodate different cations. However, alternating syn-anti arrangement of bases
      along a chain as well as in a quartet is maintained through out the MD
      simulation. Coordinated Na+ ions, within the quadruplex cavity are quite mobile
      within the central channel and can even enter or exit from the quadruplex core,
      whereas coordinated K+ ions are quite immobile. MD studies at 400K indicate that
      K+ ion cannot come out from the quadruplex core without breaking the terminal G
      tetrads. Smaller grooves in antiparallel structures are better binding sites for
      hydrated counter ions, while a string of hydrogen bonded water molecules are
      observed within both the small and large grooves. The hydration free energy for
      the K+ ion coordinated structure is more favourable than that for the Na+ ion
      coordinated antiparallel quadruplex structure.

PMID- 11334104
TI  - Structure-function relationship of three triple-helical nucleic acids.
AB  - The nucleic acid triplexes poly d(T) x poly d(A) x poly d(T), poly (U) x poly (A)
      x poly (U), and poly (I) x poly (A) x poly (I) display a sort of continuity
      between each other. However, their morphologies present their own individuality
      which, considering those of their parent duplexes, are quite unexpected. This
      comparison helps to understand triplex structure-function relationship. While
      helical parameters are functions of the sugar pucker, low values of WC and
      Hoogsteen base-pair propellers is commonplace for triplexes and the Hoogsteen
      base-pair geometry monitors the effects of the interstrand phosphates charge
      charge repulsion.

PMID- 11334105
TI  - Interactions of meso-tetra-(4-N-oxyethylpyridyl) porphyrin, its 3-N analog and
      their metallocomplexes with duplex DNA.
AB  - Interactions of meso-tetra-(4-N-oxyethylpyridyl) porphyrin (TOEPyP(4)), its 3-N
      analog (TOEPyP(3)) and their Co, Cu, Ni, Zn metallocomplexes with duplex DNA have
      been investigated by uv/visible absorbance and circular dichrosim spectroscopies.
      Results reveal the interactions of these complexes with duplex DNA are of two
      types. (1) External binding of duplex DNA by metalloporphyrins containing Zn and
      Co, and (2) Binding of duplex DNA both externally and internally (by
      intercalation) by porphyrins not containing metals, and metalloporphyrins
      containing Cu and Ni. Results indicate that (4N-oxyethylpyridyl) porphyrins
      intercalate more preferably in the structure of duplex DNA and have weaker
      external binding than 3N-porphyrins.

PMID- 11334106
TI  - Binding of bis-linked netropsin derivatives in the parallel-stranded hairpin form
      to DNA.
AB  - Cis-diammine Pt(II)- bridged bis-netropsin and oligomethylene-bridged bis
      netropsin in which two monomers are linked in a tail-to-tail manner bind to the
      DNA oligomer with the sequence 5'-CCTATATCC-3' in a parallel-stranded hairpin
      form with a stoichiometry 1:1. The difference circular dichroism (CD) spectra
      characteristic of binding of these ligands in the hairpin form are similar. They
      differ from CD patterns obtained for binding to the same duplex of another bis
      netropsin in which two netropsin moieties were linked in a head-to-tail manner.
      This reflects the fact that tail-to-tail and head-to-tail bis-netropsins use
      parallel and antiparallel side-by-side motifs, respectively, for binding to DNA
      in the hairpin forms. The binding affinity of cis-diammine Pt(II)-bridged bis
      netropsin in the hairpin form to DNA oligomers with nucleotide sequences 5'
      CCTATATCC-3' (I), 5'-CCTTAATCC-3' (II), 5'-CCTTATTCC-3' (III), 5'-CCTTTTTCC-3'
      (IV) and 5'-CCAATTTCC-3' (V) decreases in the order I = II > III > IV > V . The
      binding of oligomethylene-bridged bis-netropsin in the hairpin form follows a
      similar hierarchy. An opposite order of sequence preferences is observed for
      partially bonded monodentate binding mode of the synthetic ligand.

PMID- 11334107
TI  - Mixed mode of ligand-DNA binding results in S-shaped binding curves.
AB  - S-shaped binding curves often characterize interactions of ligands with nucleic
      acid molecules as analyzed by different physico-chemical and biophysical
      techniques. S-shaped experimental binding curves are usually interpreted as
      indicative of the positive cooperative interactions between the bound ligand
      molecules. This paper demonstrates that S-shaped binding curves may occur as a
      result of the "mixed mode" of DNA binding by the same ligand molecule. Mixed mode
      of the ligand-DNA binding can occur, for example, due to 1) isomerization or
      dimerization of the ligands in solution or on the DNA lattice, 2) their ability
      to intercalate the DNA and to bind it within the minor groove in different
      orientations. DNA-ligand complexes are characterized by the length of the ligand
      binding site on the DNA lattice (so-called "multiple-contact" model). We show
      here that if two or more complexes with different lengths of the ligand binding
      sites could be produced by the same ligand, the dependence of the concentration
      of the complex with the shorter length of binding site on the total concentration
      of ligand should be S-shaped. Our theoretical model is confirmed by comparison of
      the calculated and experimental CD binding curves for bis-netropsin binding to
      poly(dA-dT) poly(dA-dT). Bis-netropsin forms two types of DNA complexes due to
      its ability to interact with the DNA as monomers and trimers. Experimental S
      shaped bis-netropsin-DNA binding curve is shown to be in good correlation with
      those calculated on the basis of our theoretical model. The present work provides
      new insight into the analysis of ligand-DNA binding curves.

PMID- 11334108
TI  - From RNA world to protein: an eagle's eye view of the role of guanosine in
      tracing the antiquity of the intron.

PMID- 11334109
TI  - Conformational dynamics of subtilisin-chymotrypsin inhibitor 2 complex by coarse
      grained simulations.
AB  - An off-lattice dynamic Monte Carlo (MC) method is used to investigate the
      conformational dynamics of chymotrypsin inhibitor 2 (CI2) and subtilisin in both
      free and complex forms over two time windows, referring to short and long time
      scales. The conformational dynamics of backbone bonds analysed from several
      independent trajectories reveal that: Both the inhibitor and the enzyme are
      restricted in their bond rotations, excluding a few bonds, upon binding; the
      effect being greatest for the loop regions, and for the inhibitor. A
      cooperativity in the near-neighbor bond rotations are observed on both time
      scales, whereas the cooperative rotations of the bonds far along the sequence
      appear only in the long time window, and the latter time window is where most of
      the interactions between the inhibitor and the enzyme are observed. Upon binding,
      the cooperatively rotating parts of the inhibitor and the enzyme are readjusted
      compared to their free forms, and new correlations appear. The binding loop,
      although it is the closest contact region, is not the only part of the inhibitor
      involved in the interactions with the enzyme. Loops 3 and 8 and the helices F and
      G in bound enzyme and the binding loop of the inhibitor contribute at the most to
      the collective motions of whole structure on the slow time scale and are
      apparently important for enzyme-inhibitor interactions and function. The results
      in general provide evidence for the contribution of the loops with cooperative
      motions to the extensive communication network of the complex.

PMID- 11334110
TI  - Conformational space comparison of GnRH and lGnRH-III using molecular dynamics,
      cluster analysis and Monte Carlo thermodynamic integration.
AB  - The conformational space available to GnRH and lGnRH-III was compared using 5.2
      ns constant temperature and pressure molecular dynamics simulations with explicit
      TIP3P solvation and the AMBER v. 5.0 force field. Cluster analysis of both
      trajectories resulted in two groups of conformations. Results of free energy
      calculations, in agreement with previous experimental data, indicate that a
      conformation with a turn from residues 5 through 8 is preferred for GnRH in an
      aqueous environment. By contrast, a conformation with a helix from residues 2
      through 7 with a bend from residues 6 through 10 is preferred for lGnRH-III in an
      aqueous environment. The side chains of His2 and Trp3 in lGnRH-III occupy
      different regions of phase space and participate in weakly polar interactions
      different from those in GnRH. The unique conformational properties of lGnRH-III
      may account for its specific anti cancer activity.

PMID- 11334111
TI  - Substrate specificity plays an important role in uncoupling the catalytic and
      scaffolding activities of rat testis DNA topoisomerase IIalpha.
AB  - Topoisomerase II (topo II) is a dyadic enzyme found in all eukaryotic cells. Topo
      II is involved in a number of cellular processes related to DNA metabolism,
      including DNA replication, recombination and the maintenance of genomic
      stability. We discovered a correlation between the development of postnatal
      testis and increased binding of topo IIalpha to the chromatin fraction. We used
      this observation to characterize DNA-binding specificity and catalytic properties
      of purified testis topo IIalpha. The results indicate that topo IIalpha binds a
      substrate containing the preferred site with greater affinity and, consequently,
      catalyzes the conversion of form I to form IV DNA more efficiently in contrast to
      substrates lacking such a site. Interestingly, topo IIalpha displayed high
      affinity and cooperativity in binding to the scaffold associated region. In
      contrast to the preferred site, however, high-affinity binding of topo IIalpha to
      the scaffold-associated region failed to result in enhanced catalytic activity.
      Intriguingly, competition assays involving scaffold-associated region revealed an
      additional DNA-binding site within the dyadic topo IIalpha. These results
      implicate a dual role for topo IIalpha in vivo consistent with the notion that
      its sequestration to the chromatin might play a role in chromosome condensation
      and decondensation during spermatogenesis.

PMID- 11334112
TI  - Structure and stability of the insulin dimer investigated by molecular dynamics
      simulation.
AB  - Molecular dynamics simulation indicates that the dynamical behaviour of the
      insulin dimer is asymmetric. Atomic level knowledge of the interaction modes and
      protein conformation in the solvation state identifies dynamical structures, held
      by hydrogen bonds that stabilize, mainly in one monomer, the interaction between
      the chains. Dynamic cross-correlation analysis shows that the two insulin
      monomers behave asymmetrically and are almost independent. Solvation energy,
      calculated to evaluate the contribute of each interface residue to the dimer
      association pattern, well compares with the experimental association state found
      in protein mutants indicating that this parameter is an important factor to
      explain the association properties of mutated insulin dimers.

PMID- 11334113
TI  - Solution structure of an immunoactive peptide fragment of Staphylococcal protein
      A.
AB  - Staphylococcal protein-A (SpA) is known to bind the Fc fragment of immunoglobin G
      in vitro and induce a myriad of immunogenic responses in vivo. The latter is
      ascribed to be due to the interaction of Fc and SpA. It has also been proposed
      that in vivo proteolytically cleaved fragments of SpA may be functioning in the
      same manner. One such fragment (EQQNAFYEILHLPNLNEEQR), fragment 8-27 of the B
      domain (SpA-B), was recently shown to exhibit in vivo immunogenic response
      [Sinha, P., Sengupta, J., and Ray, P. K. (1999) Biochem. Biophys. Res. Commun.
      258, 141-147]. As a first step towards understanding the mode of interaction of
      this peptide with the Fc fragment, we have studied the solution conformation of
      this isolated peptide by CD and NMR. The peptide, with 7 contact residues in the
      crystal structure of the SpA-B/Fc complex and comprising of mostly helixI and
      part of helixII of the 3-helix bundle of SpA-B, was found to be present
      predominantly in extended structure. However it showed nascent turn/helix like
      conformations around F14 & Y15. These two residues are known to play a vital role
      in SpA-B/Fc interaction as deciphered from crystal structure and NMR studies of
      SpA-B/Fc complex and mutational studies. The implications of our results,
      especially the nascent conformations found around F14 & Y15, in design of SpA-B
      mimetic small molecules are discussed.

PMID- 11334114
TI  - International consensus statement on idiopathic pulmonary fibrosis.

PMID- 11334115
TI  - In defence of the carbon monoxide transfer coefficient Kco (TL/VA).
AB  - The carbon monoxide transfer factor (TL,co) is the product of the two primary
      measurements during breath-holding, the CO transfer coefficient (Kco) and the
      alveolar volume (VA). Kco is essentially the rate constant for alveolar CO uptake
      (Krogh's kco), and in healthy subjects, increases when VA is reduced by
      submaximal inflation, or when pulmonary blood flow increases. Recently, new
      reference values were proposed for clinical use which included the observed VA at
      full inflation; this was claimed to "eliminate the need for Kco". In this
      commentary, some mechanisms e.g. respiratory muscle weakness, lung resection,
      diffuse alveolar damage and airflow obstruction, which decrease or increase total
      lung capacity (TLC) are reviewed. Even when alveolar structure and function are
      normal, the change in Kco at a given VA varies according to the underlying
      pathophysiological mechanism. The advantages and disadvantages of normalizing Kco
      and TL,co to predisease predicted TLC or to the patient's actual VA (using lack
      of expansion or loss of alveolar units models) are considered. Examination of
      carbon monoxide transfer coefficient and alveolar volume separately provides
      information on disease pathophysiology which cannot be obtained from their
      product, the carbon monoxide transfer factor.

PMID- 11334116
TI  - High short-term mortality following lung biopsy for usual interstitial pneumonia.
AB  - Usual interstitial pneumonia (UIP) is a specific histological pattern of
      interstitial pneumonia most often associated with the clinical syndrome of
      idiopathic pulmonary fibrosis (IPF). There is controversy regarding the use of
      surgical lung biopsy in the diagnosis of UIP, and the risk of lung biopsy in
      these patients is largely unknown. This study investigated the 30 day surgical
      mortality rate in patients undergoing surgical lung biopsy for UIP. Patients
      undergoing surgical lung biopsy over a 10-yr period from 1986-1995 with the
      ultimate diagnosis of UIP (with or without underlying connective tissue disease)
      were identified. Pathology, computed tomography, medical records, and survival
      were assessed. Ten of sixty patients with usual interstitial pneumonia were found
      to be dead within 30 days of surgical biopsy. All of these were patients with
      idiopathic UIP, unassociated with connective tissue disease (clinical condition
      of IPF). In conclusion, patients with usual interstitial pneumonia of the
      idiopathic type, who present with atypical features, may be at higher risk for
      death following surgical biopsy than patients presenting with more typical
      features or patients with other interstitial illnesses.

PMID- 11334117
TI  - Upregulation of Fas-signalling molecules in lung epithelial cells from patients
      with idiopathic pulmonary fibrosis.
AB  - The caspase cascade is an executioner of apoptosis, mediated by Fas. Fas
      associating protein with death domain (FADD) interacts with Fas and initiates
      apoptosis through activating caspase-8. It has previously been demonstrated that
      the Fas-Fas ligand pathway may be involved in the pathophysiology of idiopathic
      pulmonary fibrosis (IPF). The aim of this study was to investigate Fas-signalling
      molecules in epithelial cells in IPF. The immunohistochemistry for FADD and
      caspase-1 and -3 and terminal deoxynucleotidyl transferase-mediated
      deoxyuridinetriphosphate nick endlabelling (TUNEL) methods were performed in lung
      tissues from 10 patients with IPF obtained by thoracoscopic biopsy and in seven
      normal lung parenchyma specimens. The induction of caspases expression and
      activation by Fas-ligation on lung epithelial cell line A549 was also
      investigated. The immunoreactivity grade for FADD and caspase-1 and -3, and
      positive signals for TUNEL were significantly increased in epithelial cells of
      IPF compared with controls. Fas-ligation induced upregulation of caspase-1 and -3
      expression in the nucleus and cytoplasm in A549 cells. Procaspase-1, -3, and -8
      were activated in apoptotic cells, but not in viable cells. Although direct
      measurement of the caspase activity in lung epithelial cells of idiopathic
      pulmonary fibrosis could not be made, these results suggest that the Fas
      signalling pathway is upregulated in lung epithelial cells of idiopathic
      pulmonary fibrosis.

PMID- 11334118
TI  - Apoptotic response of eosinophils in chronic eosinophilic pneumonia.
AB  - To clarify the pathogenesis of chronic eosinophilic pneumonia (CEP), the
      apoptosis of eosinophils from bronchoalveolar lavage (BAL-Eos) was compared with
      that of eosinophils from peripheral blood (PB-Eos) in six cases of CEP. The
      survival rate of eosinophils and the percentage of apoptotic cells of both types
      of eosinophils were examined, and the effects of interleukin 5 (IL-5) were
      evaluated. The role of Fas expression in apoptosis of these eosinophils was also
      studied. The survival rate of BAL-Eos on the third day of culture was
      significantly higher than that of PB-Eos (p < 0.01). This was associated with a
      lower proportion of apoptotic cells in BAL-Eos than in PB-Eos; the percentages of
      apoptotic cells in PB-Eos and BAL-Eos after 24 h of incubation were 21.7 +/- 3.4%
      and 10.6 +/- 1.7% respectively. IL-5 suppressed apoptosis and increased the
      survival rate of both PB-Eos and BAL-Eos. It was found that the apoptotic
      character of BAL-Eos differed from that of PB-Eos in at least three ways.
      Firstly, the positive rate of Fas expression on PB-Eos was increased after 24 h
      of incubation, whereas that on BAL-Eos did not change. Secondly, the expression
      of Fas on PB-Eos was suppressed by IL-5 (18.5 +/- 4.2% - 8.3 +/- 3.2%, p < 0.05),
      whereas IL-5 failed to suppress Fas expression on BAL-Eos (3.3 +/- 1.6% - 3.6 +/-
      1.0%). Lastly, binding of antibody to Fas antigen induced apoptosis of PB-Eos,
      but not of BAL-Eos. These data suggested that Fas seemed to be involved in the
      apoptosis of PB-Eos, whereas BAL-Eos were Fas-resistant in chronic eosinophilic
      pneumonia. In conclusion, apoptosis of eosinophils might be suppressed by
      proinflammatory cytokines such as IL-5 leading to their accumulation in the lung.
      Chronic stimulation of eosinophils in the alveolar space with IL-5 may play a
      crucial role chronic eosinophilic disorders.

PMID- 11334119
TI  - Hypertonic saline alters ion transport across the human airway epithelium.
AB  - Aerosolized hypertonic saline is currently being investigated as a new agent for
      the treatment of impaired mucociliary clearance which occurs in many respiratory
      diseases. Mannitol aerosols, in particular dry powder inhalers, have been
      proposed as an alternative treatment to saline, offering the same osmotic load
      with other benefits. However, the effects of these hypertonic aerosols on airway
      epithelial ion transport processes have not been tested in human subjects in
      vivo. This report examines the effect of these solutions on airway ion transport
      using the nasal potential difference (PD) technique. Seven healthy nonsmoking
      adult volunteers were studied. On different days, a dose-response curve was
      constructed for the saline added to Krebs N-[2-hydroxyethyl] piperazine-N'-[2
      ethanesulphonic acid] (HEPES) diluent. The reversibility of this saline effect
      was measured, and the response to additional saline (500 mM) and mannitol (1 M)
      compared. Hypertonic saline decreased nasal PD in a dose-related manner, with
      mean (SEM) decreases in PD (less negative) of 6.6 (1.5), 7.6 (1.6), 10.0 (2.0),
      13.1 (2.9) and 14.8 (3.2) mV (n =4) for addition of 150 mM, 250 mM, 500 mM, 1,200
      mM and 2,000 mM NaCl to the Krebs HEPES diluent, respectively. The effect of
      hypertonic saline was fully reversible with washout for 3 min (presaline 15.9
      (0.5) mV, postwashout 15.8 (1.1) mV, (n=4)). The hypertonic saline response was
      rapid in onset, sustained for at least 4 min, and decreased PD from 13.7 (1.7) mV
      to 5.1 (1.3) mV (n = 7, p < 0.001). In contrast, addition of mannitol to the
      perfusate did not significantly alter nasal PD, with a nonsignificant trend
      towards an increase (more negative) in the PD, (premannitol 13.9 (1.6) mV,
      postmannitol 15.3 (2.0) mV, n=7). As the osmotic stimulus of the 1 M mannitol is
      similar to that of the 500 mM sodium chloride, the divergent nasal potential
      difference responses suggest that the response to the saline was specific to the
      sodium chloride itself and not the simultaneous change in osmolarity. This
      demonstrates that the human airway epithelium in vivo can respond to topical
      hypertonic saline independent of the altered osmolarity.

PMID- 11334120
TI  - Defining prognostic factors in the elderly with community acquired pneumonia: a
      case controlled study of  patients aged > or = 75 yrs.
AB  - Severity assessment in the elderly with community acquired pneumonia (CAP) may be
      different compared with younger patients. In particular, age per se may not be of
      prognostic significance in older patients. A case-control study in 158 patients
      aged > or = 75 yrs with CAP was conducted to determine the factors associated
      with in-hospital mortality. Cases were drawn from all patients aged > or = 75 yrs
      with CAP who died in 1997 in five hospitals in the mid-Trent region of the UK
      (Nottingham City Hospital, University Hospital Nottingham, Derby Royal Infirmary,
      Derby City General Hospital and Kings Hill Hospital). Controls were randomly
      selected from survivors also aged > or = 75 yrs. Factors associated with
      mortality were identified following a review of the medical casenotes and the
      contribution of these factors to mortality was determined using multivariate
      analysis. Absence of fever, tachycardia and chest radiograph features of
      bilateral involvement or an effusion were independently associated with mortality
      on multivariate analysis. The British Thoracic Society (BTS) severity rule was
      50% sensitive and 64% specific in predicting death while the modified BTS rule
      displayed 67% sensitivity and 58% specificity. Age was not significantly
      associated with mortality in this group of patients aged > or = 75 yrs.
      Similarly, the clinical features employed in the British Thoracic Society rule,
      namely respiratory rate, diastolic blood pressure and blood urea, were not of
      prognostic significance and the rule itself performed poorly. The modified
      British Thoracic Society rule performed better.

PMID- 11334121
TI  - Cost-effectiveness of self-management in asthmatics: a 1-yr follow-up randomized,
      controlled trial.
AB  - Patient education in asthma can improve outcome but cost-effectiveness has not
      been widely assessed. The aim of the present study was to carry out a cost
      effectiveness analysis of patient education in asthmatics in a 12-month follow
      up. The authors randomly allocated 78 asthmatics to a control or intervention
      group after they had received ordinary outpatient consultation care. Intervention
      consisted of two 2-h group sessions followed by 1-2 individual sessions
      administered by a nurse and a physiotherapist. Self-management was emphasized.
      Effectiveness was expressed in terms of quality of life and forced expiratory
      volume in one second (FEV1). Doctor visits, days off work, dispensed
      pharmaceuticals, hospital admissions, travel costs, time costs and educational
      costs were recorded. The control and intervention groups induced mean total costs
      of Norwegian Krone (NOK) 16,000 and 10,500 per patient, respectively. A 10-unit
      improvement in St. George's Respiratory Questionnaire total score and a 5%
      improvement in FEV1 in the intervention group were associated with a saving of
      NOK 3,400 and 4,500, respectively, compared to the control group. The number
      needed to educate (NNE) to make one person symptom free was associated with a
      saving of NOK 12,200. The results were robust to realistic changes in the
      assumptions upon which they were based. It could be concluded from this study
      that patient education in asthmatics in a 12-month follow-up improved patient
      outcomes and reduced costs.

PMID- 11334122
TI  - Clinical diagnosis of current asthma: predictive value of respiratory symptoms in
      the SAPALDIA study. Swiss  Study on Air Pollution and Lung Diseases in Adults.
AB  - Bronchial asthma is a very common disease which often remains underdiagnosed. The
      aim of this study was to determine the predictive value of the most common
      respiratory symptoms and to explore the best symptom combinations to predict
      diagnosis of asthma. A questionnaire comprising common respiratory symptoms was
      submitted to 9,651 subjects aged 18-60 yrs, randomly selected from the Swiss
      population, of whom 225 subjects (2.3%) had current asthma as confirmed by their
      general practitioner. Based on these data the authors calculated the predictive
      values of single symptoms and symptom combinations to diagnose asthma. Wheezing
      was the most sensitive single symptom (sensitivity 75%). Simple symptoms such as
      wheezing with dyspnoea, chronic phlegm or chronic cough had specificity greater
      than 95%. Wheezing with dyspnoea (WD) or nocturnal dyspnoea (ND) had the best
      positive predictive value (PPV) as isolated symptoms (24% and 21%, respectively).
      When combining symptoms, wheezing associated with daily dyspnoea at rest or
      nocturnal dyspnoea showed the best PPV (42% and 39%, respectively), almost double
      single symptoms such as WD or ND. Wheezing associated with at least two of the
      three nocturnal symptoms (nocturnal dyspnoea, nocturnal cough or nocturnal chest
      tightness) had a sensitivity of 80% to diagnose asthma. In conclusion,
      respiratory symptoms obtained by medical history are reliable predictors of
      asthma. The findings suggest that particular combinations of symptoms are
      clinically useful in the differential diagnosis of asthma.

PMID- 11334123
TI  - Correlation of airway obstruction and patient-reported endpoints in clinical
      studies.
AB  - To establish the correlation among asthma efficacy parameters over a long period,
      data from over 1,500 patients in two one-year asthma clinical trials with
      montelukast, a Cys-LT1 antagonist, were analysed. Airway obstruction
      measurements, forced expiratory volume in one second (FEV1) and peak expiratory
      flow (PEF), were measured at clinic visits. Patients recorded daytime symptom
      score, "as-needed" beta-agonist use, and PEF on a daily basis. Relationships
      among these parameters at baseline and during the one-year treatment period were
      established by correlation analyses. Multiple correlations between the airway
      obstruction (FEV1 and PEF) and patient-reported measurements were evaluated by
      canonical correlation analysis. Pairwise correlations of the efficacy parameters
      over a one-year time period were stable. Canonical correlation between the airway
      obstruction and patient-reported asthma efficacy endpoints was low, indicating
      that each category of endpoints measures a distinctively different aspect of the
      disease. It appears that at least one endpoint from each category should be used
      in asthma clinical studies.

PMID- 11334124
TI  - Improved delivery of fenoterol plus ipratropium bromide using Respimat compared
      with a conventional metered dose inhaler.
AB  - Asthma can be effectively treated by the use of bronchodilator therapies
      administered by inhalation. The objective of this study was to describe the dose
      response relationship of combined doses of fenoterol hydrobromide (F) and
      ipratropium bromide (I) (F/I) delivered via Respimat, a soft mist inhaler, and to
      establish the Respimat dose which is as efficacious and as safe as the standard
      marketed dose of F/I (100/40 microg) which is delivered via a conventional
      metered dose inhaler (MDI). In a double-blind (within device) cross-over study
      with a balanced incomplete block design, 62 patients with stable bronchial asthma
      (mean forced expiratory volume in one second (FEV1) 63% predicted) were
      randomized at five study centres to receive five out of eight possible
      treatments: placebo, F/I 12.5/5, 25/10, 50/20, 100/40 or 200/80 microg delivered
      via Respimat; F/I 50/20 or 100/40 microg delivered via MDI. Pulmonary function
      results were based on the per-protocol dataset, comprising 47 patients. All F/I
      doses produced greater increases in FEV1 than placebo. A log-linear dose-response
      was obtained for the average increase in FEV1 up to 6 h (AUC0-6 h) and peak FEV1
      across the dose range administered by Respimat. Statistically, therapeutic
      equivalence was not demonstrated between any F/I dose administered by Respimat
      compared with the MDI. However 12.5/5 and 25/10 microg F/I administered via
      Respimat were closest (slightly superior) to the F/I dose of 100/40 microg
      delivered via MDI. Pharmacokinetic data from 34 patients indicated a two-fold
      greater systemic availability of both drugs following inhalation by Respimat
      compared to MDI. In general, the active treatments were well tolerated and safe
      with regard to vital signs, electrocardiography, laboratory parameters and
      adverse events. In conclusion, combined administration of fenoterol hydrobromide
      and ipratropium bromide via Respimat, is as effective and as safe as higher doses
      given via a metered dose inhaler.

PMID- 11334125
TI  - Beta agonists, inhaled steroids, and the risk of intensive care unit admission
      for asthma.
AB  - Although inhaled corticosteroid (ICS) use is associated with a decreased risk of
      hospitalization for asthma, the impact of ICS on the risk of life-threatening
      asthma exacerbation is less clear. The effect of ICS and inhaled beta agonist
      (IBA) dispensing on the risk of intensive care unit admission for asthma, a
      surrogate for life-threatening exacerbation, is evaluated. Using computerized
      International classification of diseases (ICD)-9 discharge diagnoses, a cohort of
      all 2,344 adult Northern California members of a health maintenance organization
      hospitalized for asthma over a 2-yr period were identified. Computerized pharmacy
      data was used to ascertain asthma medications dispensed during the 3-,6-, and 12
      month intervals preceding index hospitalization for asthma. During the 3-months
      preceding hospitalization, a minority of subjects had no IBA units dispensed
      (34%), with 14% receiving low level (1 unit), 20% medium level (2-3 units), and
      32% high level (> or = 4 units) therapy. A substantial proportion received no ICS
      units (55%), whereas 13% had low, 16% medium, and 15% high level therapy. In
      multiple logistic regression analysis, high level IBA use was associated with a
      greater risk of intensive care unit (ICU) admission for asthma after controlling
      for asthma severity. There was no relationship, however, between low or medium
      level IBA use and ICU admission. Conversely, medium level and high level ICS use
      were associated with a reduced risk of ICU admission. Analysing 6- and 12-month
      medication dispensing data, similar risk patterns were observed. Inhaled
      corticosteroid dispensing was associated with reduced risk of intensive care unit
      admission among adults hospitalized for asthma, whereas the opposite applied for
      high dose beta agonist usage. This suggests that ICS prescription to adults with
      moderate-to-severe asthma could reduce the risk of life-threatening exacerbation.

PMID- 11334126
TI  - Mycoplasma pneumoniae and Chlamydia pneumoniae infections in children with
      pneumonia. Mowgli Study Group.
AB  - The most common clinical signs, host responses and radiographic patterns were
      studied in 203 Italian children hospitalized for community-acquired pneumonia in
      order to clarify the role of clinical and radiological characteristics in the
      diagnosis of Mycoplasma pneumoniae and/or Chlamydia pneumoniae infections.
      Antibody measurements in paired sera and polymerase chain reaction on
      nasopharyngeal aspirates were used to establish the diagnoses of acute M.
      pneumoniae and C. pneumoniae infection, and the aetiologic data were correlated
      with the clinical, laboratory and radiographic data obtained on admission. No
      significant association was observed between evidence of M. pneumoniae and/or C.
      pneumoniae infection and periods of episode during the year, mean age of the
      study subjects, individual symptoms, physical findings or laboratory test
      results. Furthermore, no significant correlation was observed in relation to the
      radiological findings and M. pneumoniae and/or C. pneumoniae infection. This
      study shows that neither clinical findings nor laboratory parameters
      distinguished Mycoplasma pneumoniae and/or Chlamydia pneumoniae infection in
      children with pneumonia. Radiological findings also have a limited capacity to
      differentiate aetiologic agents. The priorities for future research include the
      development of rapid, easily accessible and cost-effective diagnostic tests
      useful for each episode of pneumonia in children.

PMID- 11334127
TI  - Histamine challenges discriminate between symptomatic and asymptomatic children.
      MAS-Study Group. Multicentre Allergy Study.
AB  - The aims of this study were to investigate a threshold value for bronchial
      responsiveness in children aged 7 yrs, which discriminates between symptomatic
      and asymptomatic children, and to identify determinants of this responsiveness.
      Titrated bronchial histamine challenges using the reservoir method were performed
      in 645 children aged 7 yrs, from the birth cohort Multicentre Allergy Study
      (MAS). When defining a reference population of healthy children within the MAS
      cohort, the 95th percentile of the provocative concentration causing a 20% fall
      in forced expired volume in one second PC20 among these asymptomatic study
      subjects amounted to 0.60 mg x mL(-1). This resulted in a specificity of 93.0%
      and a sensitivity of 45.9%, for discriminating between "current wheezers" and
      "non-current wheezers". Determinants of airway responsiveness at this age were
      pulmonary function, sensitization to indoor allergens, total immunoglobulin E and
      current wheeze. The results indicate that a very low cut-off provocative
      concentration causing a 20% fall in forced expired volume in one second (<1.0 mg
      x mL(-1)) defines airway hyperresponsiveness in children aged 7 yrs using the
      reservoir method. Provocation protocols for histamine challenges in this age
      group should therefore start with concentrations markedly below 1.0 mg x mL(-1).

PMID- 11334129
TI  - Leak compensation in positive pressure ventilators: a lung model study.
AB  - Leak compensating abilities of six different positive pressure ventilators
      commonly used to deliver noninvasive positive pressure ventilation, including the
      bilevel positive airway pressure (BiPAP) S/T-D and Quantum (Respironics Inc,
      Murrysville, PA, USA), 335 and O'NYX (Mallinckrodt Inc, St Louis, MO, USA), PLV
      102 (Respironics), and Siemens Servo 900C (Siemens Inc, Danvers, MA, USA). Using
      a test lung model, compensatory capabilities of the ventilators were tested for
      smaller and larger leaks using the assist/control or timed modes. Back-up rate
      was 20 min(-1), inspiratory pressure was 18 cmH2O, and expiratory pressure was 5
      cmH2O. It was found that even in the absence of air leaking, delivered tidal
      volume differed substantially between the ventilators during use of pressure
      targeted modes, depending on inspiratory flows, inaccuracies in set versus
      delivered pressures, and inspiratory duration. Also during pressure-targeted
      ventilation, increasing the tI/ttot up to, but not beyond, 0.5 improved
      compensation by lengthening inspiratory duration, whereas use of a sensitive flow
      trigger setting tended to cause autocycling during leaking, interfering with
      compensation. Leaking interfered with cycling of the BiPAP S/T, inverting the I:E
      ratio, shortening expiratory time, and reducing delivered tidal volume. Volume
      targeted modes achieved limited compensation for small air leaks, but compensated
      poorly for large leaks. To conclude, leak-compensating capabilities differ
      markedly between ventilators but pressure-targeted ventilators are preferred for
      noninvasive positive pressure ventilation in patients with substantial air
      leaking. Adequate inspiratory flows and durations should be used, triggering
      sensitivity should be adjusted to prevent autocycling, and a mechanism should be
      available to limit inspiratory time and avoid I:E ratio inversion.

PMID- 11334128
TI  - Parents' quality of life and respiratory symptoms in young children with mild
      wheeze. EASE Study Group.
AB  - The Paediatric Asthma Caregiver's Quality of Life Questionnaire (PACQLQ),
      measures the impact of child asthma symptoms on family activity (CGAct) and
      parental anxiety (CGEmot). It has not been validated for families of children <7
      yrs, with wheezing illness. This study assessed the sensitivity of the PACQLQ to
      symptom change in 62 preschool children with wheezing illness. The median age of
      children was 3 yrs (range 0.8-6 yrs). At entry and 3-month follow-up, parents
      recorded child respiratory symptoms in a 1-month diary and completed the PACQLQ.
      On average, children in the study had 7 symptomatic days per month. On entry,
      mothers < or = 30 yrs had worse scores than those > 30 (p < 0.02), and mothers in
      less affluent socioeconomic groups had worse scores than those in higher groups
      (p = 0.05). Change in symptom scores and symptom free days between entry and
      follow-up was associated with change in PACQLQ scores (r = 0.54-0.57, p <0.001).
      Thirty-three parents had absolute change in PACQLQ of <0.5 over three months
      (which has been previously defined as not being clinically significant). Compared
      to parents with higher PACQLQ change, parents with PACQLQ scores <0.5, did not
      differ in frequency of child symptoms or in social-demographic factors, but had
      better quality of life scores on entry to the study (p<0.01). It is concluded
      that the Paediatric Asthma Caregiver's Quality of Life Questionnaire is sensitive
      to group measures of child symptom change over 3 months, among preschool
      children, and this supports its use as an outcome measure in clinical trials. The
      absolute impact of child symptoms on parent quality of life varies among parents.

PMID- 11334130
TI  - Functional differences in bi-level pressure preset ventilators.
AB  - The performance of four bilevel positive pressure preset ventilators was
      compared. The ventilators tested were; BiPAP ST30 (Respironics); Nippy2 (B + D
      Electrical); Quantum PSV (Healthdyne); and Sullivan VPAP H ST (Resmed). A patient
      simulator was used to determine the sensitivity of the triggering mechanisms and
      the responses to a leak within the patient circuit, and to changes in patient
      effort. Significant differences (p <0.05) between the devices were seen in the
      trigger delay time and inspiratory trigger pressure. When a leak was introduced
      into the patient circuit, the fall in tidal volume (VT) was less than ten per
      cent for each ventilator. The addition of patient effort produced a number of
      changes in the ventilation delivered. Patient efforts of 0.25 s induced a
      variable fall in VT. An increase in VT was seen with some ventilators with
      patient efforts of 1 s but the effect was variable. Trigger failures and
      subsequent falls in minute volume were seen with the BiPAP and the Nippy2 at the
      highest respiratory frequency. Differences in the responses of the ventilators
      are demonstrated that may influence the selection of a ventilator, particularly
      in the treatment of breathless patients with ventilatory failure.

PMID- 11334131
TI  - Systemic inflammatory response after bronchoalveolar lavage in critically ill
      patients.
AB  - Bronchoscopic bronchoalveolar lavage (BAL) may be followed by a systemic
      inflammatory response. Previous reports have suggested pneumonia as a
      predisposing condition and systemic cytokines as possible mediators. To test this
      hypothesis, systemic levels of interleukin (IL)-1beta, IL-6 and tumour necrosis
      factor-alpha (TNF-alpha) were studied before and at 12 h and 24 h after
      bronchoscopically guided BAL in 30 mechanically ventilated patients (median age
      67 (range 54-76) yrs, simplified acute physiology score II (SAPS II) 33 (12-56)),
      20 of whom had pneumonia and 10 of whom were control patients without pneumonia.
      Arterial oxygen partial pressure to inspired oxygen fraction ratio (Pa,O2/FI,O2),
      body temperature, mean arterial pressure, and cardiac frequency were recorded.
      The majority of patients (28/30, 93%) received antibiotic treatment prior to the
      procedure. Pa,O2/FI,O2 ratio was lower at 12 h compared to baseline in patients
      with pneumonia (baseline median 192 (range 65-256); 12 h 160 (66-190) mmHg,
      p<0.001) and ventilated controls (baseline 293 (205-473); 12 h 226 (153-330) mm
      Hg p=0.011), but returned to baseline levels at 24 h (pneumonia: 194 (92-312),
      p=0.991; controls: 309 (173-487) mmHg, p=0.785). No changes in other clinical
      variables were observed. Systemic TNF-alpha levels before BAL (pneumonia: 35 (10
      88); controls: 17 (0-33) pg x mL(-1)) did not increase at 12 h (pneumonia: 35 (0
      64); p=0.735; controls: 16 (0-21) pg x mL(-1), p=0.123 comparison to baseline) or
      24 h (pneumonia: 31 (0-36), p=0.464; controls: 19 (0-43) pg x mL(-1), p=0.358).
      No changes of IL-1beta (baseline: pneumonia 0 (0-13); controls 1 (0-32) pg x mL(
      1)) or IL-6 (baseline: pneumonia, 226 (9-4300); controls, 53 (0-346) pg x mL(-1))
      were detected. No deterioration of clinical variables and no increase in systemic
      cytokine release has been observed after bronchoalveolar lavage, in critically
      ill patients. The potential cytokine increase is probably too small, in relation
      to the pre-existing inflammatory response, to yield clinical significance in this
      population otherwise antibiotic therapy may have been protective.

PMID- 11334132
TI  - Interlobar differences in bronchoalveolar lavage fluid from children with cystic
      fibrosis.
AB  - Bronchoalveolar lavage (BAL) performed in specialist centres has improved the
      understanding of infant cystic fibrosis (CF) lung disease. As most researchers
      sample from a single lobe, it was determined whether BAL results could be
      generalized to other lung segments. Thirty-three CF children, aged 1.5-57 months,
      underwent in random order sequential BAL of their right middle and lingula lobes.
      Specimens from each lobe had separate quantitative bacteriology, cytology and
      cytokine analysis. Bacterial counts > or = 1 x 10(5) colony forming units (cfu) x
      mL(-1) were observed in nine (27%) subjects, including six involving only the
      right middle lobe. These six children had similar inflammatory indices in their
      right middle and lingula lobes, and interleukin (IL)-8 concentrations in the
      latter were significantly higher than that observed within the lingula lobes of
      the 24 CF children with bacterial counts < 1 x 10(5) cfu x mL(-1). Lingula
      neutrophil and IL-8 levels correlated best with right middle lobe bacteria
      numbers. This observational study in cystic fibrosis children suggests that while
      inflammation is detected in both lungs, bacterial distribution may be more
      inhomogeneous. Bronchoalveolar lavage microbiological findings from a single lobe
      may therefore, not be generalized to other lung segments. When performing
      bronchoalveolar lavage in cystic fibrosis children, it is important to sample
      from multiple sites.

PMID- 11334133
TI  - Inhaled corticosteroids reduce growth. Or do they?
AB  - The class label warning in the United States for inhaled corticosteroids (ICS's)
      states that these drugs may reduce growth velocity in children. In this paper,
      the evidence for this warning is reviewed from a clinical point of view. Children
      with asthma tend to grow slower than their healthy peers during the prepubertal
      years because they go into puberty at a later age. However, asthmatic children do
      achieve a (near) normal adult height. In randomized controlled clinical trials,
      the use of inhaled beclomethasone, budesonide and fluticasone is associated with
      a reduced growth during the first months of therapy, in the order of magnitude of
      approximately 0.5-1.5 cm x yr(-1). It is, however, unlikely that such an effect
      continues or persists because accumulating evidence shows that asthmatic
      children, even when they have been treated with ICS for years, attain normal
      adult height. Individual rare cases have been reported, however, where ICS use
      was associated with clinically relevant growth suppression. Inhaled
      corticosteroids are the most effective therapy available for maintenance
      treatment of childhood asthma. Fear of reduced growth velocity is based on
      exceptional cases and not on group data. It should, therefore, not be a reason to
      withhold or withdraw such highly effective treatment in children with asthma.

PMID- 11334134
TI  - Burkholderia cepacia: current clinical issues, environmental controversies and
      ethical dilemmas.
AB  - Burkholderia cepacia is a plant phytogen and is known as a hardy and versatile
      organism. Over the past two decades it has emerged as a pathogen in the cystic
      fibrosis (CF) community, with devastating effects. Pulmonary colonisation can
      lead to an accelerated decline in lung function. In some cases, it causes a rapid
      and progressive pneumonic illness termed "cepacia syndrome", which is untreatable
      and fatal. B. cepacia is inherently resistant to multiple antibiotics and highly
      transmissible and virulent strains have been identified. CF patients colonised
      with the organism have to be segregated from their peers to try to prevent cross
      infection. However, the pathogenicity of B. cepacia is not limited to CF. Other
      groups, such as individuals with chronic granulomatous disease and
      immunocompromised patients are vulnerable and it has caused disease in healthy
      individuals. However, the agricultural and petrochemical industries are
      attempting to exploit properties of B. cepacia for use as a biopesticide and
      biodegradation agent. This article provides an up to date review of clinically
      based literature on the Burkholderia cepacia complex, highlighting clinical
      management issues for both cystic fibrosis and non-cystic fibrosis patients. The
      article also addresses the potential conflict between medicine and agriculture on
      plans to reintroduce strains of Burkholderia cepacia back into the environment.

PMID- 11334135
TI  - Plethysmographic measurements of lung volume and airway resistance. ERS/ATS Task
      Force on Standards for Infant Respiratory Function Testing. European Respiratory
      Society/ American Thoracic Society.
AB  - Functional residual capacity (FRC) is the only static lung volume that can be
      measured routinely in infants. It is important for interpreting volume-dependent
      pulmonary mechanics such as airway resistance or forced expiratory flows, and for
      defining normal lung growth. Despite requiring complex equipment, the
      plethysmographic method for measuring FRC is very simple to apply and, unlike the
      gas dilution techniques, enables repeat measures of lung volume to be obtained
      within a few minutes. This method has the further advantage that with suitable
      adaptations to the equipment, simultaneous measurements of airway resistance can
      also be obtained. The aim of this paper is to provide recommendations pertaining
      to equipment requirements, study procedures and reporting of data for
      plethysmographic measurements in infants. Implementation of these recommendations
      should help to ensure that such measurements are as accurate as possible and that
      meaningful comparisons can be made between data collected in different centres or
      with different equipment. These guidelines cover numerous aspects including
      terminology and definitions, equipment, data acquisition and analysis and
      reporting of results and also highlight areas where further research is needed
      before consensus can be reached.

PMID- 11334136
TI  - Acute psychosis after CPAP treatment in a schizophrenic patient with sleep apnoea
      hypopnoea syndrome.
AB  - A 52-yr-old man with a residual phase of schizophrenia developed sleep apnoea
      hypopnoea syndrome (SAHS). After five days of continuous positive airway pressure
      (CPAP) treatment, the patient developed an aggressive mood with incoherence,
      prominent hallucinations and agitation, and attempted to hit his relatives. He
      was finally admitted to the hospital with an acute psychotic episode. Withdrawal
      of CPAP, and neuroleptic treatment controlled the episode, and clinical symptoms
      of SAHS reappeared 10 days later. Schizophrenia associated to sleep apnoea
      hypopnoea syndrome has rarely been reported, but, to the authors' knowledge, the
      induction of a psychotic episode by continuous positive airway pressure treatment
      in a patient with sleep apnoea-hypopnoea syndrome and coexisting schizophrenia
      has never been previously reported.

PMID- 11334137
TI  - Vascular smooth muscle cell phenotypes in primary pulmonary hypertension.
AB  - Primary pulmonary hypertension (PPH) is associated with specific structural
      alterations, including cellular intimal thickening, intimal fibrosis, and
      plexiform lesions. To determine the phenotypes of smooth muscle cells (SMCs) in
      such lesions, the authors conducted an immunohistochemical analysis of lung
      tissues from two patients with PPH, using two antimuscle actin antibodies, HHF35
      and CGA7, and two anti-SMC myosin heavy chain markers, anti-SM1 and anti-SM2
      antibodies and related antibodies. Cells that stained positive (+) with HHF35,
      CGA7, anti-SM1, and anti-SM2 were considered to be SMCs of a mature state.
      Conversely, those that stained positive with HHF35 and anti-SM1, but weakly
      positive (+/-) or negative (-) with CGA7 and anti-SM2, were considered to be SMCs
      exhibiting an immature state. Cellular intimal thickening was composed of SMCs of
      an immature phenotype (HHF35+, CGA7+/-, SM1+, SM2+/-), accompanied by the
      expression of fibronectin and the presence of macrophages; intimal fibrosis
      contained mature SMCs (HHF35+, CGA7+, SM1+, SM2+); and plexiform lesion consisted
      of proliferative endothelial cells (von Willebrand factor-positive cells,
      proliferating cell nuclear antigen-positive cells) and underlying immature SMCs
      (HHF35+, CGA7-, SM1+, SM2-) associated with fibronectin expression and macrophage
      infiltration. These findings suggest that smooth muscle cells with specific
      phenotypes may contribute to the development of specific vascular lesions in
      primary pulmonary hypertension.

PMID- 11334138
TI  - IFN-gamma response and IL-8 plasma levels in neonates with respiratory syncytial
      virus bronchiolitis.

PMID- 11334139
TI  - ADAM17 but not ADAM10 mediates tumor necrosis factor-alpha and L-selectin
      shedding from leukocyte membranes.
AB  - The release of tumor necrosis factor-alpha (TNF-alpha) from cellular membranes
      has been shown by different laboratories to be controlled by a disintegrin and
      metalloprotease, ADAM10 or ADAM17. In contrast, only ADAM17 has shown to be
      involved in L-selectin shedding. To determine the specific roles of ADAM10 and
      ADAM17 in the processing of TNF-alpha and L-selectin shedding, antisense
      oligonucleotides (ASO) targeting both ADAM10 and ADAM17 were identified. We show
      that ISIS 16337 reduces ADAM17 mRNA and ISIS 100750 reduces ADAM10 mRNA in a
      sequence-specific and dose-dependent manner in both Jurkat and THP-1 cells. The
      ADAM17 ASO (ISIS 16337) inhibited both TNF-alpha secretion in THP-1 cells and L
      selectin shedding in Jurkat cells, whereas the ADAM10 ASO (ISIS 100750) did not
      significantly inhibit release of either protein. These results suggest that
      ADAM17 is one of the major metalloproteases involved in L-selectin shedding as
      well as TNF-alpha processing. The biologic substrates for ADAM10 in Jurkat and
      THP-1 cells remain to be elucidated.

PMID- 11334140
TI  - Propynylated phosphodiester oligonucleotides inhibit ICAM-1 expression in A549
      cells on electroporation.
AB  - Oligodeoxynucleotides (ODN) are used largely as either primers, antisense, or
      triplex-forming units. Phosphodiester ODN (PO-ODN), which are very rapidly
      degraded by exonucleases, must be protected at their ends. Even so, their life
      span inside cells is quite short. Phosphorothioate ODN (PS-ODN) are less
      sensitive to nucleases and are extensively used as antisense. Unfortunately,
      unlike PO-ODN, they interact with a number of molecules, including proteins, in
      addition to their specific nucleic acid targets. Their affinity for their target
      is lower than that of PO-ODN. PS-ODN containing propyne groups on C5 of
      pyrimidine have been shown to have a higher affinity toward their nucleic acid
      target. Here, we show that propynylated PO-ODN are more stable and much more
      efficient than their propyne-free counterparts. They are not efficient when they
      are used as lipoplexes, but they act as specific antisense on electroporation.

PMID- 11334141
TI  - Increased UV light sensitivity in transgenic Drosophila expressing the antisense
      XPD homolog.
AB  - The XPD gene is required for excision repair of UV-damaged DNA and is an
      important component of nucleotide excision repair (NER). Mutations in the XPD
      gene generate the cancer-prone syndrome xeroderma pigmentosum, Cockayne's
      syndrome, and trichothiodystrophy. XPD is a component of the TFIIH transcription
      factor, which is essential for RNA polymerase II elongation. In this work, we
      report the construction of transgenic flies overexpressing the antisense RNA of
      the Drosophila melanogaster XPD homolog (DmXPD). These flies show an increased
      sensitivity to UV radiation compared with the wild-type. This is an expected
      phenotype if the XPD function is affected and indicates that the antisense
      approach may be an alternative in the study of TFIIH functions in Drosophila.

PMID- 11334142
TI  - Optimization of hammerhead ribozymes for the cleavage of S100A4 (CAPL) mRNA.
AB  - Previously, suppression of the S100A4 mRNA by an endogenously expressed ribozyme
      in osteosarcoma cells was shown to inhibit their metastasis in rats. As a prelude
      to performing similar studies with exogenous, synthetic ribozymes, we compared a
      series of hammerhead ribozymes targeted against different sites in the mRNA. The
      ribozymes differed only in the 7-base flanking sequences complementary to the
      substrate and were protected against nucleases by chemical modification. Cleavage
      efficiency varied widely and was not obviously related to the predicted secondary
      structure of the target RNA. The most active ribozyme of the series was chosen
      for further optimization. Lengthening its flanking sequences was
      counterproductive and reduced cleavage even when using excess ribozyme. Using
      excess substrate (multiple-turnover kinetics), cleavage was fastest with the
      (6+8) ribozyme having 6 nucleotides (nt) in stem III and 8 nt in stem I. Although
      these stems strongly influence ribozyme performance, their optimization is still
      empirical. Faster cleavage was obtained by adding facilitator oligonucleotides to
      ribozymes with shorter stems of (6+6) and (5+5) nt. Stimulation was particularly
      strong in the case of the (5+5) ribozyme, which was poorly active by itself. The
      enhancement caused by different facilitator oligonucleotides paralleled their
      expected ability to hybridize to RNA as a function of length and chemical
      modification.

PMID- 11334143
TI  - Nuclease resistance and RNase H sensitivity of oligonucleotides bridged by
      oligomethylenediol and oligoethylene glycol linkers.
AB  - The properties of new chimeric oligodeoxynucleotides made of short sequences
      (tetramers, pentamers, octamers, and decamers) bridged by hexamethylenediol and
      hexaethylene glycol linkers have been investigated. These chimeric
      oligonucleotides showed an improved resistance toward snake venom 3'
      phosphodiesterase, with an increased stability when a terminal 3'-3'
      internucleotide phosphodiester bond is present. It also has been demonstrated
      that the hybrid complexes formed by bridged oligonucleotides and a complementary
      20-mer RNA are able to elicit the activity of ribonuclease H (RNase H) from
      Escherichia coli. The substrate properties of chimeric oligonucleotides depend on
      the length of the oligonucleotide fragments bridged by linkers. Introduction of a
      nonnucleotide spacer into the native oligonucleotide only slightly hampers the
      extent of the RNA hydrolysis in the hybrid complexes, whereas a modification of
      the site of reaction is observed as a possible consequence of the steric
      disturbance due to the aliphatic linkers. Hence, these new chimeric
      oligonucleotides, namely, short oligonucleotide fragments bridged by
      nonnucleotide linkers, demonstrate a favorable combination of exonuclease
      resistance and high substrate activity toward RNase H. As a consequence, these
      chimeric oligonucleotides could be proposed as new, promising analogs to be used
      in the antisense strategy.

PMID- 11334144
TI  - Evidence for higher-order structure formation by the c-myb 18-mer
      phosphorothioate antisense (codons 2-7) oligodeoxynucleotide: potential
      relationship to antisense c-myb inhibition.
AB  - We have demonstrated the formation of higher-order structures (presumably
      tetraplexes) by an 18-mer phosphorothioate antisense c-myb
      oligodeoxyribonucleotide that has been shown to have activity in the treatment of
      leukemia xenograft models. Although not observable by conventionally employed
      techniques, such as PAGE and dimethyl sulfate (DMS) protection, the formation of
      such higher-order structures by this oligonucleotide was revealed by several
      techniques. These included capillary gel electrophoresis (CGE), which
      demonstrated the presence of molecules with greatly increased retention time
      compared with the monomer; magnetic circular dichroism spectroscopy, which
      demonstrated a band at 290 nm, a characteristic of antiparallel tetraplexes; and
      fluorescence energy transfer measurements. For the last, the 18-mer
      phosphorothioate oligonucleotide was synthesized with a 5'-fluorescein group.
      Similar to the molecular beacon model, its fluorescence was quenched when
      combined in solution with tetraplex-forming oligomers that contained a 3'-Dabcyl
      moiety. 7-Deazaguanosine inhibits the formation of tetraplexes by eliminated
      Hoogsteen base pair interactions. The wild-type and 7-deazaguanosine-substituted
      antisense c-myb oligomers differentially downregulated the expression of the c
      myb proto-oncogene in K562 and HL60 cells, with the wild-type oligomer being the
      least active. The 18-mer c-myb molecule can, therefore, form highly complex
      structures, whose analysis in solution cannot be limited to examination of slab
      gel electrophoresis results alone.

PMID- 11334145
TI  - Safety of intracoronary administration of c-myc antisense oligomers after
      percutaneous transluminal coronary angioplasty (PTCA).
AB  - We wished to assess the clinical safety and pharmacokinetics of ascending doses
      of a synthetic oligodeoxynucleotide (LR-3280) administered after coronary
      angioplasty. Antisense oligodeoxynucleotides designed to hybridize with target
      messenger ribonucleic acid (mRNA) in a complementary fashion to inhibit the
      expression of corresponding protein also have the ability to bind to
      extracellular growth factors. LR-3280 has been shown to reduce c-myc expression,
      inhibit growth and collagen biosynthesis in human vascular cells, and reduce
      neointimal formation in animal models of vascular injury. After successful
      percutaneous transluminal coronary angioplasty (PTCA), 78 patients were
      randomized to receive either standard care (n = 26) or standard care and
      escalating doses of LR-3280 (n = 52) (doses from 1 to 24 mg), administered into
      target vessel through a guiding catheter. Overall safety was evaluated by
      clinical adverse events, laboratory tests, and electrocardiograms. Patency was
      evaluated by quantitative coronary angiography. There were no clinically
      significant differences between treated and control patients. No adverse effects
      of LR-3280 on the patency of dilated coronary arteries were observed.
      Pharmacokinetic data revealed that peak plasma concentrations of LR-3280 occurred
      at 1 minute over the studied dose range and rapidly decreased after
      approximately1 hour, with little LR-3280 detected in the urine between 0-6 hours
      and 12-24 hours. The intracoronary administration of LR-3280 is well tolerated at
      doses up to 24 mg and produces no adverse effects in dilated coronary arteries.
      These results provide the basis for the evaluation of local delivery of this
      phosphorothioate oligodeoxynucleotide for the prevention of human
      vasculoproliferative disease.

PMID- 11334146
TI  - The 18 kDa antigen of Theileria equi is a specific but less abundant protein also
      expressed by parasites cultured in vitro.
AB  - A universally applicable test has not yet been developed for the reliable
      diagnosis of equine theileriosis, mainly because of the paucity of specific
      antigens and antigenic variation between different isolates. In this study, we
      used Theileria equi parasites cultured in vitro to identify potential diagnostic
      antigens. Using preparative isoelectric focusing to resolve the proteins in a
      lysate of infected erythrocytes, we identified an 18 kDa component of the
      parasite as a specific but poorly expressed antigen. This antigen also appears to
      have conserved epitope(s) between the isolates from the New and the Old World, as
      positive sera from both European and South American horses recognize it. The
      recombinant replica of this antigen might be a valuable tool for inclusion in the
      development strategy for a diagnostic test.

PMID- 11334147
TI  - Effect of vaccination in the field with the Theileria annulata (Hisar) cell
      culture vaccine on young calves born during the winter season.
AB  - The responses were monitored of young crossbred calves vaccinated against
      tropical theileriosis during the winter against a field tick challenge in the
      disease season. Thirty-eight calves below 2 months of age, born after the end of
      the disease season, were selected at an organized farm. Twenty-five animals were
      vaccinated with Theileria annulata (Hisar) cell culture vaccine (developed at CCS
      HAU Hisar laboratory) after the end of the disease season and 13 calves were kept
      as non-vaccinated controls. These calves were observed for their susceptibility
      to theileriosis in the new disease season. There was an increase in antibody
      titre in 18 of the 25 vaccinated animals one month after vaccination. The
      antibody titre then declined gradually, but remained higher than those of the non
      vaccinated animals at month 0. No fever or other clinical signs of tropical
      theileriosis were observed in any of the vaccinated animals. Nine out of 25 (36%)
      vaccinated calves showed occasional piroplasms (<0.5%) in blood smears. All the
      vaccinated animals withstood the field tick challenge. On the other hand, 9 of
      the 13 (69%) unvaccinated calves exhibited occasional piroplasms, and included
      three clinical cases of tropical theileriosis. These observations suggest that
      young crossbred calves vaccinated with the T. annulata (Hisar) cell culture
      vaccine at the end of the disease season were relatively resistant during the
      next disease season.

PMID- 11334148
TI  - Congenital cerebellar cortical degeneration in Holstein cattle in Southern
      Brazil.
AB  - A congenital progressive cerebellar disorder is described in Holstein calves. The
      clinical signs were progressive and were characterized by ataxia, hypermetria, a
      wide stance and fine head tremors. When the affected cattle were forced to run,
      the signs were exacerbated, leading to epileptiform attacks. Histological lesions
      consisted of a very selective cerebellar cortical degeneration, almost
      exclusively affecting the Purkinje cells. The disease affected 6 out of 200
      Holstein calves from the same bull. However, results of mating tests of the bull
      with his daughters and granddaughters suggested that it was not hereditary (p =
      0.0062) although an environmental-genetic interaction could not be ruled out.

PMID- 11334149
TI  - Pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin after
      intramuscular administration of enrofloxacin in goats.
AB  - The pharmacokinetics of enrofloxacin and its active metabolite ciprofloxacin were
      investigated in goats after a single intramuscular administration of enrofloxacin
      at 2.5 mg/kg body weight. The plasma concentrations of enrofloxacin and
      ciprofloxacin were determined simultaneously by a HPLC method. The peak
      concentrations (Cmax) of enrofloxacin (1.13 microg/ml) and ciprofloxacin (0.24
      microg/ml) were observed at 0.8 and 1.2 h, respectively. The elimination half
      life (t1/2beta), volume of distribution (Vd(area)), total body clearance (Cl(B))
      and mean residence time (MRT) of enrofloxacin were 0.74 h, 1.42 L/kg, 1329 ml/h
      per kg and 1.54 h, respectively. The t1/2beta, area under the plasma
      concentration-time curve (AUC) and the MRT of ciprofloxacin were 1.38 h, 0.74
      microg h/ml and 2.73 h, respectively. The metabolic conversion of enrofloxacin to
      ciprofloxacin was appreciable (36%) and the sum of the plasma concentrations of
      enrofloxacin and ciprofloxacin was maintained at or above 0.1 microg/ml for up to
      4 h. Enrofloxacin appears to be useful for the treatment of goat diseases
      associated with pathogens sensitive to this drug.

PMID- 11334150
TI  - Experimental mycotoxic nephropathy in pigs provoked by a diet containing
      ochratoxin A and penicillic acid.
AB  - Mycotoxic nephropathy was induced in 18 young pigs by diets contaminated with
      strains of Aspergillus ochraceus containing ochratoxin A (OTA) and penicillic
      acid (PA) at levels corresponding to those naturally encountered in animal feeds
      in Bulgaria. Haematological and biochemical parameters, as well as the
      morphological and ultrastructural changes in various internal organs, and
      especially in the kidneys, were examined at different stages of development of
      the disease. A mottled surface of the kidneys was only seen in pigs exposed to a
      mouldy diet containing 180 ppb OTA for 3 months, but microscopic lesions, as well
      as changes in various haematological and biochemical parameters, were observed in
      all groups exposed to the same mouldy diet containing only 90 or 180 ppb OTA.
      Histological examination showed two types of change: degenerative changes
      affecting the epithelial cells of the proximal tubules, which predominated at the
      initial stage, and proliferative changes in the interstitium, which predominated
      at the later stage of the disease. Telangiectasis and lymph stasis were also
      seen, as well as degenerative changes in the capillary endothelium. The
      characteristic renal lesions were similar to those observed in spontaneous cases
      of mycotoxic porcine nephropathy in Bulgaria, but they were a little different
      from the classic Danish porcine nephropathy. The enhanced toxicity of OTA in our
      study may be due to a synergistic effect between OTA and PA or to some other
      unknown metabolites produced by the same ochratoxinogenic strains of A.
      ochraceus.

PMID- 11334151
TI  - Ovine metabolism of saponins: evaluation of a method for estimating the ovine
      uptake of steroidal saponins from Narthecium ossifragum.
AB  - A sheep was dosed three times per day over six consecutive days with 70 g
      Narthecium ossifragum, and once on the seventh day with 70 g N. ossifragum.
      Additionally, it was dosed once on days 1-7 with 20 mg of [20,23,23
      2H3]sarsasapogenin. After 7 days, the sheep was killed and GC-MS analysis of the
      free and conjugated sapogenin content in bile, urine, rumen, duodenum, jejunum,
      colon and rectum samples collected from the sheep, faecal samples collected on
      days 4-7, and dosed plant material was performed. The N. ossifragum contained
      mainly sarsasapogenin and smilagenin. Only neglible levels of deuterium-labelled
      sarsasapogenins were detected in the samples from the animal. Ingested saponins
      were quickly hydrolysed in the rumen to free sapogenins and, in part, epimerized
      at C-3 to afford episapogenins. The absorption of free sapogenins appeared to
      occur in the jejunum. The concentration of sapogenins in faeces reached a plateau
      108 h after dosing started.

PMID- 11334152
TI  - Preliminary report on a single-tube, non-interrupted reverse transcription
      polymerase chain reaction for the detection of rabies virus in brain tissue.
AB  - A simple method for the rapid detection of rabies virus was developed employing a
      single-tube reverse transcription polymerase chain reaction (RT-PCR). The method
      utilized a single buffer system for both RT and PCR and was performed without
      interruption as a single thermal cycling programme. Two primer sets within the
      genes coding for rabies nucleoprotein and glycoprotein were used to amplify a 533
      bp and a 406 bp amplicon, respectively. The amplified products were detected with
      a challenge virus strain (CVS) of rabies. There was no amplified product with
      uninfected mouse or dog brain. The method was applied to detect rabies virus in
      10 mouse inoculation test (MIT)-positive and three MIT-negative brain tissue
      samples. The amplified product was found only in the MIT-positive samples. The
      amplified product was confirmed by restriction endonuclease analysis using Hinf1.
      The results from RT-PCR correlated well with the results from MIT. This indicates
      that the single-tube RT-PCR may be a useful method for detecting rabies virus in
      brain tissue samples from suspected cases of rabies.

PMID- 11334153
TI  - The environment in the provincial plan of Cremona, Italy.
AB  - Recent Italian laws mandate the consideration of environmental factors in local
      plans, especially at the provincial level of government. The plan for the
      province of Cremona in northern Italy illustrates the integration of the
      environment in provincial-level planning. The Cremona plan was developed through
      an ecological planning approach that occurred from 1994 to 1998. As part of this
      process, the planning team designed an environmental sustainability index. This
      index was integrated with an environmental capability analysis. To improve the
      quality of the Cremona landscape, the planning team developed an ecological
      network. This network seeks to weave together the natural areas of the province,
      especially by connecting provincial parks to regional river parks throughout
      Lombardy. The experience of the Cremona provincial plan has implications for
      environmental management elsewhere in Italy, Europe, and abroad.

PMID- 11334154
TI  - Turning scientific approaches into practical conservation actions: the case of
      Comunidad Indigena de Nuevo San Juan Parangaricutiro, Mexico.
AB  - Optimum natural resource management and biodiversity conservation are desirable
      goals. These, however, often exclude each other, since maximum economic benefits
      have promoted drastic reductions in biodiversity throughout the world. This
      dilemma confronts local stakeholders, who usually go for maximizing economic
      inputs, whereas other social (e.g., academic) sectors are favor conservation
      practices. In this paper we describe the way two scientific approaches--landscape
      and participatory research--were used to develop sound and durable land use
      scenarios. These two approaches included expert knowledge of both social and
      environmental conditions in indigenous communities. Our major emphasis was given
      to detect spatially explicit land use scenarios and capacity building in order to
      construct a decision support system operated by stakeholders of the Comunidad
      Indigena de Nuevo San Juan Parangaricutiro in Mexico. The system for decision
      making was fed with data from inventories of both abiotic and biotic biodiversity
      components. All research, implementation, and monitoring activities were
      conducted in close collaboration with members of the indigenous community. As a
      major result we obtained a number of forest alternative uses that favor emerging
      markets and make this indigenous community less dependent on a single market.
      Furthermore, skilled members of the community are now running the automated
      system for decision-making. In conclusion, our results were better expressed as
      products with direct benefits in local livelihoods rather than pure academic
      outputs.

PMID- 11334155
TI  - Changing approaches to mountain watersheds management in mainland South and
      Southeast Asia.
AB  - Mountain watersheds, comprising a substantial proportion of national territories
      of countries in mainland South and Southeast Asia, are biophysical and
      socioeconomic entities, regulating the hydrological cycle, sequestrating carbon
      dioxide, and providing natural resources for the benefit of people living in and
      outside the watersheds. A review of the literature reveals that watersheds are
      undergoing degradation at varying rates caused by a myriad of factors ranging
      from national policies to farmers' socioeconomic conditions. Many agencies-
      governmental and private--have tried to address the problem in selected
      watersheds. Against the backdrop of the many causes of degradation, this study
      examines the evolving approaches to watershed management and development. Until
      the early 1990s, watershed management planning and implementation followed a
      highly centralized approach focused on heavily subsidized structural measures of
      soil conservation, planned and implemented without any consultation with the
      mainstream development agencies and local people. Watershed management was either
      the sole responsibility of specially created line agencies or a project authority
      established by external donors. As a consequence, the initiatives could not be
      continued or contribute to effective conservation of watersheds. Cognizant of
      this, emphasis has been laid on integrated, participatory approaches since the
      early 1990s. Based on an evaluation of experiences in mainland South and
      Southeast Asia, this study finds not much change in the way that management plans
      are being prepared and executed. The emergence of a multitude of independent
      watershed management agencies, with their own organizational structures and
      objectives and planning and implementation systems has resulted in watershed
      management endeavors that have been in complete disarray. Consistent with the
      principle of sustainable development, a real integrated, participatory approach
      requires area-specific conservation programs that are well incorporated into
      integrated socioeconomic development plans prepared and implemented by local line
      agencies in cooperation with nongovernment organizations (NGOs) and concerned
      people.

PMID- 11334156
TI  - Golf course development in a major tourist destination: implications for planning
      and management.
AB  - The planning and design of golf course developments is influenced by many
      factors. This paper focuses on the environmental ramifications of insufficient or
      lack of compliance with standard environmental and economic planning practices.
      Specifically, it looks at a tourist destination location that was under the
      influence of extensive land development and investment speculation. The Gold
      Coast in Australia was the focal point for large overseas investment due to
      changes in government legislation regarding foreign investment. Due to the
      economic climate in the second half of the 1980s many golf course resort
      developments were built, approved, or planned. Many of these circumvented normal
      business and environment planning processes. The result has been a dangerous
      concentration of golf facilities in environmentally sensitive areas and an
      oversupply of golf facilities. Both of these matters are discussed in terms of
      the general planning process and the potential economic and environmental impacts
      to the Gold Coast and similar destinations in other parts of the world.

PMID- 11334157
TI  - Solid waste treatment as a high-priority and low-cost alternative for greenhouse
      gas mitigation.
AB  - The increased concern about environmental problems caused by inadequate waste
      management, as well as the concern about global warming, promotes actions toward
      a sustainable management of the organic fraction of the waste. Landfills, the
      most common means to dispose of municipal solid waste (MSW), lead to the
      conversion of the organic waste to biogas, containing about 50% methane, a very
      active greenhouse gas (GHG). One unit of methane has a global warming potential
      of 21 computed for a 100-year horizon or 56 computed for 20 years. The waste
      sector in Israel contributes 13% of total greenhouse gases (GHG) emissions for a
      time horizon of 100 years (for a time horizon of 20 years, the waste sector
      contribution equals to more than 25% of total GHG emissions). The ultimate goal
      is to minimize the amount of methane (CH4) by converting it to CO2. This can be
      achieved by physicochemical means (e.g., landfill gas flare, incineration) or by
      biological processes (e.g., composting, anaerobic digestion). Since the waste in
      Israel has a high organic material content, it was found that the most cost
      effective means to treat the degradable organic components is by aerobic
      composting (investment of less than US$ 10 to reduce emission of one ton CO2
      equivalent per year). Another benefit of this technology is the ability to
      implement it within a short period. The suggested approach, which should be
      implemented especially in developing countries, could reduce a significant amount
      of GHG at relatively low cost and short time. The development of a national
      policy for proper waste treatment can be a significant means to abate GHG
      emissions in the short term, enabling a gain in time to develop other means for
      the long run. In addition, the use of CO2 quotas will credit the waste sector and
      will promote profitable proper waste management.

PMID- 11334158
TI  - Print media framing of the environmental movement in a Canadian forestry debate.
AB  - In a recent paper, it was suggested that one of the reasons behind the decline in
      public regard toward British Columbia's environmental movement was an
      increasingly negative portrayal of them by the print media. To investigate this
      suggestion, we undertook a content analysis of print media reporting of forestry
      and environmental activities in the province's most widely read newspaper, the
      Vancouver Sun, during 1993 and 1997. We hypothesized that if the print media did
      contribute to the decline in public regard toward the environmental movement, we
      would find increasingly negative coverage of the environmental movement over the
      periods studied. We also hypothesized that this would be accompanied by a
      decrease in the frequency of articles dealing with issues consistent with the
      agenda of the environmental movement. We were not able to provide support for our
      initial hypothesis, nor did we observe a decrease in coverage emphasizing the
      environmental issues. We did, however, observe an increase in coverage of
      articles emphasizing typically proindustry issues with many more articles written
      with a proforestry slant in 1997 than articles written in 1993. This suggests
      that there had been an agenda shift from environmentally oriented concerns in
      British Columbia to those associated with the forest industry. As an explanation
      for the agenda shift, we point to changes in the management and reporting
      philosophy at the Vancouver Sun, the emergence of an organized, proindustry
      counterframing strategy by the BC Forest Alliance, and the implementation of
      several government policies aimed at regulating the activities of the forest
      industry.

PMID- 11334159
TI  - Building the capacity of grassroots conservation organizations to conduct
      participatory evaluation.
AB  - Stakeholder participation has become a key factor in the success of grassroots
      conservation and natural resource management programs. Yet the majority of
      program evaluations are conducted by external consultants for the purposes of
      accountability, rather than program improvement. Too often, systematic
      evaluations of conservation programs are not conducted at all. The objective of
      this study was to build the capacity of a grassroots conservation organization to
      conduct participatory evaluation, involving project stakeholders in the design,
      implementation, and use of evaluation. The study applied a conceptual model for
      participatory evaluation to the Wildlife Clubs of Kenya (WCK), the largest
      grassroots conservation program for youth in Africa, involving more than one
      million youth since 1968. Seven trainings in participatory evaluation were
      conducted with WCK staff, teachers, and community members. The 120 participants,
      representing nine WCK regions with 800 clubs, showed a significant increase in
      attitudes and knowledge regarding evaluation, as reflected by mean test scores
      before and after training. To institutionalize evaluation at WCK, existing
      organizational practices were assessed and used as a foundation for developing an
      evaluation system. Based on club competitions, a new evaluation initiative was
      launched called the WCK Incentive Program. Participants in all seven workshops
      identified indicators and sources of evidence for this evaluation system, which
      now serves as a basis for rewarding outstanding performance in WCK. This study
      revealed the importance of incentives for evaluation, the need to build on
      existing structures to promote organizational learning, and the necessity for the
      conservation community to commit resources to capacity building in participatory
      evaluation.

PMID- 11334160
TI  - Environmental impact evaluation model for industrial processes.
AB  - This paper proposes a model to evaluate the environmental impact of manufacturing
      processes. This model uses the potency factor approach to classify environmental
      impacts into five ecological health impact groups and uses their toxicological,
      cancer, and physical effects as the bases to rate the seven groups of human
      health impacts. The environmental impacts in each impact group are reported, and
      their hazard scores on ecological and human health are determined. The model also
      generates a single score for the overall environmental impacts of a process. This
      single score system helps to identify, among all the viable processes, which is
      the most environmentally friendly process. This model can serve as a tool to
      highlight the potential environmental hazards of process operations and to
      provide information about environmental performance for decision making. The
      model has been developed into a computer software program, Environmental Impact
      Evaluation System, and is demonstrated by using the processes employed for the
      manufacture of paper bags.

PMID- 11334161
TI  - Evaluation of a collaborative model: a case study analysis of watershed planning
      in the Intermountain West.
AB  - Collaborative planning processes have become increasingly popular for addressing
      environmental planning issues, resulting in a number of conceptual models for
      collaboration. A model proposed by Selin and Chavez suggests that collaboration
      emerges from a series of antecedents and then proceeds sequentially through
      problem-setting, direction-setting, implementation, and monitoring and evaluation
      phases. This paper summarizes an empirical study to evaluate if the Selin and
      Chavez model encompasses the range of factors important for the establishment and
      operation of collaboration in watershed planning from the perspective of the
      planning coordinator. Analysis of three case studies of watershed based planning
      efforts in the Intermountain West suggests the model realistically describes some
      of the fundamental collaborative elements in watershed planning. Particularly
      important factors include the involvement of stakeholders in data collection and
      analysis and the establishment of measurable objectives. Informal face-to-face
      dialog and watershed field tours were considered critical for identifying issues
      and establishing trust among stakeholders. Group organizational structure also
      seems to play a key role in facilitating collaboration. From this analysis,
      suggestions for refining the model are proposed.

PMID- 11334162
TI  - Testing the basic assumption of the hydrogeomorphic approach to assessing wetland
      functions.
AB  - The hydrogeomorphic (HGM) approach for developing "rapid" wetland function
      assessment methods stipulates that the variables used are to be scaled based on
      data collected at sites judged to be the best at performing the wetland functions
      (reference standard sites). A critical step in the process is to choose the least
      altered wetlands in a hydrogeomorphic subclass to use as a reference standard
      against which other wetlands are compared. The basic assumption made in this
      approach is that wetlands judged to have had the least human impact have the
      highest level of sustainable performance for all functions. The levels at which
      functions are performed in these least altered wetlands are assumed to be
      "characteristic" for the subclass and "sustainable." Results from data collected
      in wetlands in the lowlands of western Washington suggest that the assumption may
      not be appropriate for this region. Teams developing methods for assessing
      wetland functions did not find that the least altered wetlands in a subclass had
      a range of performance levels that could be identified as "characteristic" or
      "sustainable." Forty-four wetlands in four hydrogeomorphic subclasses (two
      depressional subclasses and two riverine subclasses) were rated by teams of
      experts on the severity of their human alterations and on the level of
      performance of 15 wetland functions. An ordinal scale of 1-5 was used to quantify
      alterations in water regime, soils, vegetation, buffers, and contributing basin.
      Performance of functions was judged on an ordinal scale of 1-7. Relatively
      unaltered wetlands were judged to perform individual functions at levels that
      spanned all of the seven possible ratings in all four subclasses. The basic
      assumption of the HGM approach, that the least altered wetlands represent
      "characteristic" and "sustainable" levels of functioning that are different from
      those found in altered wetlands, was not confirmed. Although the intent of the
      HGM approach is to use level of functioning as a metric to assess the ecological
      integrity or "health" of the wetland ecosystem, the metric does not seem to work
      in western Washington for that purpose.

PMID- 11334163
TI  - Mapping disturbances in a mangrove forest using multi-date landsat TM imagery.
AB  - To evaluate the accounts of local fishermen, Landsat TM images (1986, 1993, 1999)
      were examined to assess potential losses in the mangrove forests of the Teacapan
      Agua Brava lagoon system, Mexico. A binary change mask derived from image
      differencing of a band 4/3 ratio was employed to calculate any changes within
      this forested wetland. The results indicate that by 1986 approximately 18% (or 86
      km2) of the mangrove area under study was either dead or in poor condition. The
      majority of this damage had occurred in the eastern section of the Agua Brava
      basin, which coincides, with the reports of the elderly fishermen. Examination of
      aerial photographs from 1970 revealed no adverse impacts in this area and would
      suggest, as postulated by the fishermen and other scientists, that modifications
      in environmental conditions following the opening of a canal, Cuautla canal, in
      1972 may have initiated the large-scale mortality. Although these areas of impact
      are still developing, the results from the satellite data indicate that the
      majority of the more recent changes are occurring elsewhere in the system.
      Obvious in the 1999 satellite data, but not so in the 1993, are large areas of
      mangrove degradation in the northern section of the Teacapan region. In the Agua
      Brava basin, the more recent transformations are appearing on the western side of
      the basin. Since long-term records of environmental conditions are absent, it is
      difficult to determine why these latest changes are occurring or even if the
      earlier losses were the result of the canal. Potential agents of change that have
      recently been observed include a hurricane, a second canal, and the uncontrolled
      expansion of the Cuautla canal since 1994.

PMID- 11334164
TI  - Strul--a method for 3D alignment of single-particle projections based on common
      line correlation in Fourier space.
AB  - A central problem of 3D reconstruction in single-particle electron microscopy is
      the determination of relative orientations of the individual projections
      contributing to the reconstruction. This article describes an implementation of
      the method of common lines correlation in Fourier space that allows generation of
      common lines between an arbitrary number of projections which might posses an
      arbitrary point group symmetry. Based on this method, it is possible to optimize
      rotational and translational alignment parameters for individual single-particle
      projections. The underlying philosophy and details of implementation are
      discussed, and as an illustration a 3D reconstruction in ice of peroxisomal
      alcohol oxidase from Pichia pastoris, an octameric assembly with 422-symmetry and
      a molecular weight of 592 kDa is presented.

PMID- 11334165
TI  - An accurate analytical approach to electron crystallography.
AB  - A much more accurate analytical expression of dynamical electron diffraction than
      the phase object approximation (POA) formula has been derived in this paper which
      decreases the restriction of sample thickness up to almost one order of magnitude
      compared to POA theory. The importance of the new expression is twofold. First, a
      sample with such a thickness that new expression remains valid can be prepared
      experimentally. Second, the new expression reveals a clear and straightforward
      relationship between the wave function and crystal potential. In the expression,
      the effect of dynamical diffraction on wave function can be simply attributed to
      two factors TP(D) = (sin(lambda pi zg2))/(4pi2g2) and TA(D) = [1 - cos(lambda pi
      zg2)]/4pi2g2. Compared to the effect of transfer functions of an electron
      microscope on wave function, we found that TP(d) and TA(d) play the same role as
      transfer function but are independent of the instrument. For this reason, we here
      call the former as "extrinsic transfer functions" and the latter as "intrinsic"
      ones. In principle, one should correct not only extrinsic transfer functions but
      also intrinsic ones if one desires to achieve higher resolution.

PMID- 11334166
TI  - Correspondence analysis of sinogram lines. Sinogram trajectories in factor space
      replace raw images in the orientation of projections of macromolecular
      assemblies.
AB  - The lines of a large group of sinograms of projections with random orientation
      can be submitted to correspondence analysis. Since the number of samples per line
      is small, a small matrix is accumulated which is quick to orthogonalise. In the
      eigenvector space, the lines of a sinogram are represented by points describing a
      closed trajectory. Two trajectories of different sinograms intersect in the
      position of their common line. Determining where two trajectories cross each
      other is a problem of minimum chi2 distance in the space of 5-7 eigenvectors. An
      algorithm to determine common lines has been implemented and tested with phantom
      projections oriented at random, and corrupted with noise. The images were
      simulating a set collected with the two exposures technique, already proposed by
      the authors for three dimensional reconstruction from random projections. The
      preliminary models obtained with the new algorithm have been refined by a
      projection matching based on trajectories. This step requires determining which
      trajectory, in a set representing computed projections, matches at best with that
      of an experimental projection. This is a problem of minimum distance in a space
      with low dimensionality. The present algorithms, based on chi2 distances, run
      much faster than those based on correlation analysis and the quality of the
      reconstructed phantoms looks satisfactory.

PMID- 11334167
TI  - Imaging conditions for reliable measurement of displacement and strain in high
      resolution electron microscopy.
AB  - We analyse the degree to which the lattice fringe displacements in an image
      correspond to displacements of the atomic planes in the specimen using lens
      transfer theory. Our basic assumption is that the exit wave function faithfully
      reproduces the displacements of the projected atomic structure. The way this
      information is imaged by the objective lens is then developed analytically. We
      observe an interchange of amplitude and phase information between the original
      and the reconstructed wave function. For symmetry-related reflections, we show
      that in the absence of beam amplitude variations, the displacements are imaged
      perfectly by the objective lens. The theoretical results are confirmed using one
      dimensional simulations. For the more complicated case of non-centrosymmetric
      structures, beam tilts and crystal tilts, we study the implications for slowly
      varying displacement fields. Errors are found to be minimised in areas where the
      contrast of the lattice fringes is highest. Finally, we deduce from these
      theoretical results a number of practical rules.

PMID- 11334168
TI  - Applications of fluorescence microscopy to studies of dental hard tissue.
AB  - In this review we describe applications of fluorescence microscopy to
      investigations of dental hard tissue. Many studies have shown that human teeth
      show autofluorescence and several applications of fluorescence microscopy have
      been reported, although the chemical nature of autofluorescence remains unknown.
      However, most applications are based on a static measurement mode, which has
      inherent limitations. These limitations can be overcome by the use of time
      resolved fluorescence microscopy. Therefore, we attempted to combine ordinary and
      time-resolved fluorescence microscopy to study human dentine. Using stationary
      measurements, blue fluorescence with a peak of 440 +/- 10 nm and a width of
      approximately 100 nm was observed. Increases in fluorescence intensity were found
      to be dependent upon age and temperature, regardless of tooth type or gender. The
      results suggest that the aging mechanism for crown dentine differs from that for
      root dentine and that the observed increase in fluorescence intensity is
      partially due to a temperature-dependent physicochemical mechanism. We speculate
      that fluorescence microscopy will become a useful tool for analysis of dental
      hard tissue in several fields.

PMID- 11334169
TI  - Integrated approach of an artificial neural network and numerical analysis to
      multiple equivalent current dipole source localization.
AB  - The authors have developed a PC-based multichannel electroencephalogram (EEG)
      measurement and analysis system. This system enables us (1) to simultaneously
      record a maximum of 64 channels of EEG data, (2) to measure three-dimensional
      positions of the recording electrodes, (3) to rapidly and precisely localize
      equivalent current dipoles (ECDs) responsible for the EEG data, and (4) to
      superimpose the localization results on magnetic resonance images. A new neural
      network and numerical analysis (NNN) approach to ECD localization is described
      which integrates a feedforward artificial neural network (ANN) and a numerical
      optimization (Powell's hybrid) method. It was shown that the ANN method has the
      advantages of high-speed localization and noise robustness, because in this
      approach: (1) ECD parameters are immediately initialized from the recorded EEG
      data by the ANN and (2) ECD parameters are accurately refined by the hybrid
      method. Our multiple ECD localization method was applied to sensory evoked
      potentials and event-related potentials using the present system.

PMID- 11334171
TI  - Selective stimulation of smaller nerve fibers using biphasic rectangular pulses.
AB  - Based on the F-H model, a simulation system to study the excitation properties of
      myelinated nerve fibers was developed. In order to minimize electrochemical
      damage of nerve tissue, three selective stimulation methods employing biphasic
      rectangular pulses were studied, which use single, double and triple electrodes,
      respectively. The simulation results prove that all of the three methods are
      effective in selective stimulation of smaller nerve fibers in a compound nerve
      trunk under certain conditions. The feasibility of these methods is also verified
      by animal experiments on the sciatic nerve trunks of toads. The amplitude and
      delay of compound action potential and the results of collision experiments
      proved that the methods are valid. These methods will be very useful in
      functional neuromuscular stimulation.

PMID- 11334170
TI  - Control of arterial partial pressure of oxygen in patients with respiratory
      abnormalities using an adaptive observer.
AB  - A system for controlling the arterial partial pressure of oxygen in patients on
      long-term oxygen therapy is proposed. After performing a parameter estimation of
      the model of pulmonary system, an adaptive observer is applied to perform the
      control task. The observer considers the model uncertainties as disturbances and
      rejects their impact on the system. As a result of this, the quality of the
      control can be drastically improved. The presented simulation and experimental
      results show the effectiveness of the proposed scheme. The proposed control
      scheme is applicable without preliminary adjustment of the control parameters.

PMID- 11334172
TI  - Analysis of heart rate variability of an anencephalic fetus using a new method to
      determine a fractal dimension of non-stationary time-serial data.
AB  - Human fetal heart rate (HR) variabilities were analyzed using the QIS-A, which we
      devised to determine a fractal dimension of non-stationary time series. Fifteen
      10-min HR data of an anencephalic fetus at 23 weeks and 3 days of gestation and
      those of 10 normal fetuses at the same weeks of gestation were obtained by
      ultrasonic cardiography. The anencephalus preserved the spinal cord, medulla and
      partial anterior hypothalamus. The fractal scaling exponent alpha of the
      anencephalus was compared with that of each normal fetus by Student's t-test. In
      results, the scaling relationship in each case had a crossover pattern
      characterized by alpha(s) and alpha(l), which were slopes above and below a
      crossover point, respectively. Differences in mean alpha(s) and mean alpha(l)
      between the anencephalus and each normal fetus were significant (P < 0.01): mean
      alpha(s), 1.0 +/- 0.1 (+/-SD) (1/f fluctuation) and 1.6 +/- 0.2 (+/-SEM); mean
      alpha(l), 1.6 +/- 0.2 (+/-SD) and 1.4 +/- 0.1 (+/-SEM). There were six
      significant differences in mean crossover point between the anencephalus and each
      normal fetus: 13.8 +/- 5.7 s (+/-SD) and 15.3 +/- 5.6 s (+/-SEM). These results
      reveal the relationship between fractal structure of fetal HR variability and the
      developing central nervous system (CNS). In particular, the 1/f fluctuation of HR
      variability in an anencephalic fetus from the 1.25 to 13.8 s time scale might
      have a strong relation to the defect of the CNS.

PMID- 11334173
TI  - Characteristics of acoustic noise in echo-planar imaging.
AB  - Characteristics of the acoustic noise generated by magnetic resonance imagers of
      different systems and performance levels were studied when operating in echo
      planar imaging (EPI) sequence. Continuous equivalent A-weighted sound pressure
      levels (Leq) and peak impulse sound pressure levels (Lpeak) during EPI were
      measured in 12 clinical super-conducting MRI systems (0.5-1.5 T). Sound pressure
      levels and frequency spectra of EPI were compared with those of nine different
      pulse sequences. EPI sound pressure levels differed among institutions (Leq =
      94.2 +/- 2.7 dBA. Lpeak = 109.1 +/- 3.5 dB), but these were within permissible
      noise exposure levels. Sound pressure levels during EPI were not significantly
      different from those during other pulse sequences. However, compared to other
      pulse sequences. EPI had a significantly greater proportion of acoustic noise in
      the high octave-frequency band. Single-shot EPI had relatively higher frequency
      noise and greater Leq than multishot EPI, but the difference in Leq decreased
      when the number of slices in multishot EPI was increased.

PMID- 11334174
TI  - Evaluation of the sharpness of concentric needle electrodes by a penetration
      test.
AB  - This paper deals with a method to evaluate the sharpness of the concentric needle
      electrode (CNE) and the consistency of sharpness on repeated penetration. An
      aluminum foil of standard thickness and properties was used as the penetration
      medium. A load profile was obtained as a function of time, and has been
      correlated with the shape and quality of grinding of the tip of the CNE. This
      load profile can be used as a quality evaluation method. This method is utilized
      for the assessment of the impairment of the needle tip on repeated penetration
      and hence for comparison of different needle electrode models.

PMID- 11334175
TI  - Human genomic research promoted by industry consortium.

PMID- 11334176
TI  - Firms targeting the growing nursing care business.

PMID- 11334177
TI  - Health Ministry denies fault on Creutzfeldt Jacob disease-linked dura mater
      transplants.

PMID- 11334178
TI  - Detecting binocular 3D motion in static 3D noise: no effect of viewing distance.
AB  - Relative binocular disparity cannot tell us the absolute 3D shape of an object,
      nor the 3D trajectory of its motion, unless the visual system has independent
      access to how far away the object is at any moment. Indeed, as the viewing
      distance is changed, the same disparate retinal motions will correspond to very
      different real 3D trajectories. In this paper we were interested in whether
      binocular 3D motion detection is affected by viewing distance. A visual search
      task was used, in which the observer is asked to detect a target dot, moving in
      3D, amidst 3D stationary distractor dots. We found that distance does not affect
      detection performance. Motion-in-depth is consistently harder to detect than the
      equivalent lateral motion, for all viewing distances. For a constant retinal
      motion with both lateral and motion-in-depth components, detection performance is
      constant despite variations in viewing distance that produce large changes in the
      direction of the 3D trajectory. We conclude that binocular 3D motion detection
      relies on retinal, not absolute, visual signals.

PMID- 11334179
TI  - An implicit measure of undetected change.
AB  - Several paradigms (e.g. change blindness, inattentional blindness, transsaccadic
      integration) indicate that observers are often very poor at reporting changes to
      their visual environment. Such evidence has been used to suggest that the spatio
      temporal coherence needed to represent change can only occur in the presence of
      focused attention. However, those studies almost always rely on explicit reports.
      It remains a possibility that the visual system can implicitly detect change, but
      that in the absence of focused attention, the change does not reach awareness and
      consequently is not reported. To test this possibility, we used a simple change
      detection paradigm coupled with a speeded orientation discrimination task. Even
      when observers reported being unaware of a change in an item's orientation, its
      final orientation effectively biased their response in the orientation
      discrimination task. Both in aware and unaware trials, errors were most frequent
      when the changed item and the probe had incongruent orientations. These results
      demonstrate that the nature of the change can be represented in the absence of
      awareness.

PMID- 11334180
TI  - Visual field asymmetries in attention and learning.
AB  - It has been suggested that attentional resolution is greater in the lower than in
      the upper visual field. As there is no corresponding asymmetry between the areas
      in the primary visual cortex where the input from upper and lower visual fields
      is processed, an 'attentional filter' has been proposed to act in one or more
      higher visual cortical areas in order to constrict the availability of visual
      information to the level of awareness. To investigate this, a visual search array
      was presented to the entire visual field and reaction times from upper and lower
      visual fields compared. In a second experiment, subjects were trained in
      detecting targets in different visual fields. There was no significant difference
      between reaction times for targets presented in either upper or lower visual
      fields when the array was presented to the entire visual field. However, when the
      array was restricted to either the upper or lower visual fields, reaction times
      were significantly slower for detection in the upper visual field.

PMID- 11334181
TI  - The effects of dot density and motion coherence on perceptual fading of a target
      in noise.
AB  - A peripherally presented target embedded in dynamic texture perceptually
      disappears (or 'fills-in') after around 10 s of steady fixation. This phenomenon
      was investigated for a target containing moving dots. The effects of manipulating
      the coherence of the motion within the target and the density of dots across the
      whole screen were explored. Coherence thresholds for the detection of a target at
      different dot densities were recorded for comparison. Fading occurred faster as
      either motion coherence or dot density was reduced. Coherence thresholds for
      target detection were unaffected by manipulations of dot density. There appeared
      to be no relationship between the stimulus exposure time needed for fading and
      the coherence threshold for detection of a target. The results suggest that the
      time taken for a target to fade is not a simple function of its motion detection
      threshold.

PMID- 11334182
TI  - On the manifestations of memory in visual search.
AB  - Evidence is presented supporting the thesis that performance in visual search
      tasks is affected by the contribution of memory processes. Three levels of
      analysis, corresponding to the various time scales present in a typical search
      experiment, are discussed. Perceptual learning involves the task and stimulus
      specific improvement seen across blocks of training. Trial-to-trial priming has
      an influence which extends over 5-8 trials and lasts on the order of 30 s. Within
      trial tagging prevents the re-inspection of already attended (or fixated) items.
      Also at the within-trial level of analysis, parallel accumulation of evidence for
      target presence/absence or target location inherently involves memory mechanisms.
      Organizing the various phenomena in this way makes it apparent that the various
      mechanisms may interact in a causal way. Within-trial tagging may contribute to
      priming which may contribute to perceptual learning. Recent proposals that visual
      search is memoryless (amnesic) are discussed and dismissed.

PMID- 11334183
TI  - Selective attention, ideal observer theory and 'early' visual channels.

PMID- 11334184
TI  - Co-adsorbed fibrinogen and von Willebrand factor augment platelet procoagulant
      activity and spreading.
AB  - Previously we observed that platelets adherent to surfaces preadsorbed with blood
      plasma exhibited 1.3 to 2.4 times greater procoagulant activity than platelets on
      surfaces adsorbed with fibrinogen (Fg) only. These observations suggested that
      the adhesion proteins adsorbed from plasma may activate platelets in a
      cooperative, or synergistic manner. In the present study, polystyrene surfaces
      adsorbed with both Fg and vWF induced up to three times greater procoagulant
      activity than surfaces adsorbed with Fg or vWF only. The amounts of Fg and vWF
      adsorbed from binary mixtures that resulted in increased procoagulant activity
      were found to be similar to the amounts that adsorbed to PS from 100% plasma. The
      effect of adsorbed adhesion proteins on platelet spreading was also investigated.
      The proportion of fully spread platelets increased, depending on the adhesion
      protein preadsorbed to the surface, in the following order: vWF < Fg < Fn < (vWF
      + Fg) < Vn < plasma.

PMID- 11334185
TI  - Scaffold design and fabrication technologies for engineering tissues--state of
      the art and future perspectives.
AB  - Today, tissue engineers are attempting to engineer virtually every human tissue.
      Potential tissue-engineered products include cartilage, bone, heart valves,
      nerves, muscle, bladder, liver, etc. Tissue engineering techniques generally
      require the use of a porous scaffold, which serves as a three-dimensional
      template for initial cell attachment and subsequent tissue formation both in
      vitro and in vivo. The scaffold provides the necessary support for cells to
      attach, proliferate, and maintain their differentiated function. Its architecture
      defines the ultimate shape of the new grown soft or hard tissue. In the early
      days of tissue engineering, clinically established materials such as collagen and
      polyglycolide were primarily considered as the material of choice for scaffolds.
      The challenge for more advanced scaffold systems is to arrange cells/tissue in an
      appropriate 3D configuration and present molecular signals in an appropriate
      spatial and temporal fashion so that the individual cells will grow and form the
      desired tissue structures--and do so in a way that can be carried out
      reproducibly, economically, and on a large scale. This paper is not intended to
      provide a general review of tissue engineering, but specifically concentrate on
      the design and processing of synthetic polymeric scaffolds. The material
      properties and design requirements are discussed. An overview of the various
      fabrication techniques of scaffolds is presented, beginning with the basic and
      conventional techniques to the more recent, novel methods that combine both
      scaffold design and fabrication capabilities.

PMID- 11334186
TI  - Polyamide 6 composite membranes: properties and in vitro biocompatibility
      evaluation.
AB  - The aim of the present study was to develop polyamide 6 membrane blended with
      gelatin and chondroitin sulfate using the phase precipitation method and evaluate
      its in vitro biocompatibility. Morphology of membranes was studied by laser
      scanning confocal microscopy which allowed the nondestructive visualization of
      internal bulk morphology of membranes. Membranes exhibited porous morphology with
      pores spanning across the membrane width with interconnections at various depths.
      Membranes showed adequate mechanical properties with tensile strengths of 20.10
      +/- 0.64 MPa, % strain of 3.01+/-0.07, and modulus of 1082.50+/-23.50 MPa. In
      vitro biocompatibility of membranes by direct contact test did not show
      degenerative effects on NIH3T3 cells and also its leach-out products (LOP), as
      determined by tetrazolium (MTT) and neutral red uptake (NRU) assay. Mouse
      peritoneal macrophage cultured in contact with membranes and PTFE control showed
      comparable expression of activation markers such as CD11b/CD18, CD45, CD14, and
      CD86 suggesting the membranes' non-activating nature. Membrane LOP did not induce
      excessive proliferation of mouse splenocytes suggesting its non-antigenic nature.
      Preliminary blood compatibility of membranes was observed with no detectable
      hemolysis in static incubation assay. Taken collectively, the present data
      demonstrate that polyamide 6 composite membranes are biocompatible and
      prospective candidates for tissue engineering applications.

PMID- 11334187
TI  - Synthesis, characterization, biodegradation, and drug delivery application of
      biodegradable lactic/glycolic acid polymers. Part II: biodegradation.
AB  - A series of previously-synthesized lactic/glycolic acid polymers (PLGA) with
      various molar ratios of lactic to glycolic acid and various molecular weights
      were further studied with regard to their biodegradation behavior, and in
      particular, the factors affecting the biodegradation rate. The biodegradation of
      PLGA is affected by many factors including polymer composition, molecular weight,
      and nature of the incubating media. The biodegradation rate of PLGA containing
      higher content of lactic acid moiety is lower than those containing a lower
      content of lactic acid moiety. PLGAs with a higher molecular weight, degrade
      faster than those with a lower molecular weight, i.e. the molecular weight
      decreases more rapidly for higher molecular weight PLGAs than their lower
      molecular weight counterparts. Nature or properties of the hydrolysis/incubating
      media may have an effect on the biodegradation of PLGAs. A basic medium may slow
      down the biodegradation of PLGA in comparison with samples in an acidic medium.
      The rate of pH reduction for the incubating medium can be divided into three
      deferent phases, giving an inverted S-type pH profile for the non-buffered
      incubating media.

PMID- 11334189
TI  - Poly(ethylene terephthalate) yarn with antibacterial properties.
AB  - Poly(ethylene terephthalate) (PET) yarn with grafted poly(acrylic acid)
      (poly(AA)) was loaded with [6R-[6alpha,7beta(Z)]]-7-[[2-amino-4
      thiazolyl)(methoxy-imino)acetyl]aminol-8-oxo-3-[[(1,2,5,6-tetrahydro-2-methyl-5,6
      dioxo-1,2,4-triazin-3-yl)thio]-methyl]-5-thia-1-azabicyclo[4.2.0] oct-2-ene-2
      carboxylic acid (Lendacin), a cephalosporin-type antibiotic. Immobilization of
      Lendacin was due to ionic interactions. Drug loading was varied from 0.61 to
      5.29% wt/wt. The release of Lendacin from the modified PET fibers to water was
      monitored for 550 h. Variations of Lendacin concentration in water were
      approximated with a double exponential equation (CL = Cinfinity[a[1 - exp(
      k1tau)] + b[1 - exp(-k2tau)]]) describing fast initial burst followed by slow
      release of Lendacin. In vitro studies revealed that the drug loaded fibers were
      bioactive against Staphylococcus auras, Escherichia coli, and Pseudomonas
      aureginosa.

PMID- 11334188
TI  - Copolymers of trimethylene carbonate and epsilon-caprolactone for porous nerve
      guides: synthesis and properties.
AB  - Copolymers of trimethylene carbonate and epsilon-caprolactone were synthesized
      and characterized with the aim of assessing their potential in the development of
      a flexible and slowly degrading artificial nerve guide for the bridging of large
      nerve defects. The effect of the monomer ratio on the physical properties of the
      polymers and its influence on the processability of the materials was
      investigated. Under the applied polymerization conditions (130 degrees C, 3 days
      using stannous octoate as a catalyst) high molecular weight polymers (Mn above 93
      000) were obtained. All copolymers had glass transition temperatures below room
      temperature. At trimethylene carbonate contents higher than 25 mol% no
      crystallinity was detected. A decrease in crystallinity resulted in the loss of
      strength and decrease in toughness, as well as in an increased polymer
      wettability. Amorphous poly(trimethylene carbonate), however, showed excellent
      ultimate mechanical properties due to strain-induced crystallization (Tm = 36
      degrees C). Low crystallinity copolymers could be processed into dimensionally
      stable porous structures by means of immersion precipitation and by combination
      of this technique with the use of porosifying agents. Porous membranes of
      poly(trimethylene carbonate) could be prepared when blended with small amounts of
      high molecular weight poly(ethylene oxide). Poly(trimethylene carbonate) and
      poly(trimethylene carbonate-co-epsilon-caprolactone) copolymers with high epsilon
      caprolactone content possess good physical properties and are processable into
      porous structures. These materials are most suitable for the preparation of
      porous artificial nerve guides.

PMID- 11334190
TI  - Analytical characterization of collagen- and/or hydroxyapatite-modified
      polypyrrole films electrosynthesized on Ti-substrates for the development of new
      bioactive surfaces.
AB  - The design and development of new bioactive surfaces on titanium-based materials
      employed in orthopedic implants is described. The new biosurfaces consist of thin
      polypyrrole films, directly grown on implant materials and modified by the
      inclusion of hydroxyapatite and/or collagen during the polymer electrodeposition
      step. The experimental procedure has been optimized in terms of loading and
      distribution of the bioactive components. X-ray photoelectron spectroscopy (XPS)
      and scanning electron microscopy (SEM) investigations have been performed in
      order to control the effectiveness of film modifications. In particular, XPS has
      been used to check the presence of biocompounds in the surface and sub-surface
      region of the polymer film, which is a critical requisite for a positive
      interface interaction between the biomaterial and the surrounding tissue.

PMID- 11334192
TI  - Quantum mechanical quantitative structure activity relationships to avoid
      mutagenicity in dental monomers.
AB  - The objective of this study was to identify through quantum mechanical
      quantitative structure activity relationships (Q-QSARs) chemical structures in
      dental monomers that influence their mutagenicity. AMPAC, a semiempirical
      computer program that provides quantum mechanical information for chemical
      structures, was applied to three series of reference chemicals: a set of
      methacrylates, a set of aromatic and a set of aliphatic epoxy compounds. QSAR
      models were developed using this chemical information together with mutagenicity
      data (Salmonella TA 100, Ames Test). CODESSA, a QSAR program that calculates
      quantum chemical descriptors from information generated by AMPAC and
      statistically matches these descriptors with observed biological properties was
      used. QSARs were developed which had r2 values exceeding 0.90 for each study
      series. These QSARs were used to accurately predict the mutagenicity of BISGMA. a
      monomer commonly used in dentistry, and two epoxy monomers with developing use in
      dentistry, GY-281 and UVR-6105. The Q-QSAR quantum mechanical descriptors
      correctly predicted the level of mutagenicity for all three compounds. The
      descriptors in the correlation equation pointed to components of structure that
      may contribute to mutagenesis. The QSARs also provided 'dose windows' for testing
      mutagenicity, circumventing the need for extensive dose exploration in the
      laboratory. The Q-QSAR method promises an approach for biomaterials scientists to
      predict and avoid mutagenicity from the chemicals used in new biomaterial
      designs.

PMID- 11334191
TI  - Controlled release of growth factors based on biodegradation of gelatin hydrogel.
AB  - To develop a carrier for the controlled release of biologically-active growth
      factors, biodegradable hydrogels were prepared through glutaraldehyde cross
      linking of gelatin with isoelectric points (IEP) of 5.0 and 9.0, i.e. 'acidic'
      and 'basic' gelatins, respectively. Radioiodinated growth factors were used to
      investigate their sorption and desorption from the hydrogel of both types of
      gelatin. Basic fibroblast growth factor (bFGF) and transforming growth factor
      beta1 (TGF-beta1) were well sorbed with time to the acidic gelatin hydrogel,
      while less sorption was observed for the basic gelatin hydrogel. This could be
      explained in terms of the electrostatic interaction between the growth factors
      and the acidic gelatin. However, bone morphogenetic protein-2 (BMP-2) and
      vascular endothelial growth factor (VEGF), though their IEPs are higher than 7.0,
      were sorbed to the acidic gelatin hydrogel to a smaller extent than the two other
      growth factors. Under in vitro non-degradation conditions, approximately 20% of
      the incorporated bFGF and TGF-beta1 was desorbed from the hydrogels within the
      initial 40 min, followed by no further substantial desorption, whereas large
      initial desorption was observed for BMP-2 and VEGF. When implanted in the back
      subcutis of mice, gelatin hydrogels were degraded over time. Each growth factor
      was retained in vivo being incorporated in the acidic gelatin hydrogel: the
      smaller the in vitro desorption amount from the hydrogel, the longer the in vivo
      retention time. The in vivo profile of bFGF and TGF-beta1 retention was in good
      accordance with that of the hydrogel. These findings indicate that the growth
      factor immobilized to the acidic gelatin hydrogel through ionic interaction was
      released in vivo as a result of hydrogel degradation.

PMID- 11334193
TI  - Cardiac surgical patients exposed to heparin-bonded circuits develop less
      postoperative cerebral dysfunction than patients exposed to non-heparin-bonded
      circuits.
AB  - A prospective randomized trial was used to study the incidence of cerebral
      dysfunction in patients undergoing cardiopulmonary bypass (CPB) with heparin
      bonded vs non-heparin-bonded circuits. Although the etiology of postoperative
      cerebral dysfunction is controversial, activation of the systemic inflammatory
      response may play a role. After institutional approval and informed written
      consent, 39 elective coronary artery bypass (CABG) patients were studied. A
      battery of neuropsychometric tests (NPMTs) was performed preoperatively, and 5
      days and 6 weeks postoperatively. Significant change in NPMT performance was
      defined as a 25% or greater decrease in postoperative performance, compared to
      baseline. The number of abnormal tests per patient was calculated. Analysis using
      the Mann-Whitney rank test was performed for the first follow-up. Patients
      randomized to heparin-bonded circuits had fewer abnormal NPMTs (>1 abnormal test)
      on postoperative day 5 (58 vs 70%, n=19 and 20) than patients randomized to non
      heparin-bonded circuits. Patients exposed to heparin-bonded circuits had fewer
      abnormal tests (>1 abnormal test) at 6 weeks (36 vs 63%, n=14 and 16). Results
      suggested that the attenuation of systemic inflammation by heparin-bonded CPB
      circuits may lower the incidence of cerebral injury in cardiac surgical patients.

PMID- 11334194
TI  - Treatment of sepsis in cardiac surgery: role of immunoglobulins.
AB  - Cardiopulmonary bypass (CPB) is associated with an injury that may cause
      pathophysiological changes such as systemic inflammatory response syndrome,
      multiple organ dysfunction syndrome, and mediator-induced multiorgan failure.
      Systemic endotoxinaemia, release of proinflammatory cytokines, and interactions
      between neutrophils and endothelium have been reported to correlate with a high
      incidence of organ dysfunction, infection and sepsis following cardiac surgery.
      This review discusses the dysregulation of the immune response as a major reason
      for the higher susceptibility to infections following cardiac surgery, various
      treatment strategies to reduce CPB-induced inflammation, and especially the
      prophylactic use of immunoglobulins in cardiac surgery.

PMID- 11334195
TI  - The side-effects of cardiopulmonary bypass on the lungs: changes in
      bronchoalveolar lavage fluids.
AB  - Although technical refinements have improved the safety of cardiac operations,
      postoperative dysfunction of lung and other organs occurs frequently after
      cardiopulmonary bypass (CPB). The aim of the present study was to search the
      aetiopathogenesis of pulmonary complications due to CBP. Ten patients with stable
      coronary artery disease, undergoing coronary artery bypass grafting (CABG)
      surgery, were included in the study. Forty bronchoalveolar lavage (BAL) fluid
      samplings were performed in the 10 patients. Samples were obtained at the
      following time periods: (1) preoperatively; (2) at the end of the first hour
      after anaesthetic induction; (3) at the conclusion of 30 min of crossclamp on
      CPB; and (4) at the conclusion of 20 h after the end of CPB, postoperatively.
      Cell contents of bronchoalveolar lavage fluid, alveolar macrophage viability,
      eosinophil cationic protein (ECP) levels and myeloperoxidase (MPO) concentrations
      were analysed in each bronchoalveolar lavage fluids. While the percentage of
      preoperative macrophages was 85.90% and the percentage of preoperative
      neutrophils was 2.40%, they were 77.00% and 11.30% in the postoperative samples,
      respectively. Mean alveolar macrophage viability was 96.20% preoperatively and
      90.40% in the postoperative period. Preoperative eosinophil cationic protein mean
      concentration was < 2 microg/l and mean response value (RV) was 28.80.
      Preoperative mean myeloperoxidase concentration was 7.66 ng/ml. Postoperative
      eosinophil cationic protein mean response value was 63.40 and mean
      myeloperoxidase concentration was 59.25 ng/ml. There were significant differences
      between third and final samples with regard to both neutrophil percentages (p =
      0.028) and MPO levels (p = 0.005). While the preoperative mean PaO2 value was
      89.39 mmHg and mean SaO2 value was 97.12%, they were calculated in the
      postoperative arterial blood specimens of patients, without inhaling O2, as 65.31
      mmHg and 93.84%. These changes between blood gas analyses reflect the impairment
      of the lungs (p = 0.009 and p = 0.007, respectively). Neither alveolar macrophage
      viability nor ECP levels changed significantly between consecutive periods.
      However, when the results of the first and fourth samples were compared, we saw
      the cumulative effects of CPB, in that alveolar macrophages lost their viability
      and ECP mean RVs rose. These changes were statistically significant (p = 0.027
      and p = 0.013, respectively). However, postoperative ECP levels were not like
      those found in a patient with asthma. Also, changes between alveolar macrophage
      percentages (p = 0.028), between neutrophil percentages (p = 0.036) and between
      MPO concentrations (p = 0.005) were statistically significant. Again, changes in
      neutrophil percentages between first and final samples correlated with changes in
      MPO levels between same periods (r = 0.657, p = 0.039).

PMID- 11334196
TI  - Albumin in the pump prime: its effect on postoperative weight gain.
AB  - An investigation was conducted to determine whether adding albumin to the prime
      of the cardiopulmonary bypass circuit had any effect on postoperative weight
      gain. Patients undergoing non-emergency myocardial revascularization for coronary
      artery disease were divided into two groups. Group I (albumin) received 250 ml of
      5% human albumin in their pump prime, whereas group II (control) served as
      controls. The same surgeon, anesthesia technique, perfusion circuit and conduct,
      and postoperative management were employed for all patients in the study. No
      statistically significant differences could be found between the groups for any
      of the variables studied, including fluid intake during surgery and the first 24
      h postoperation, urine output, fluid balance and postoperative weight gain. The
      authors conclude from this investigation that adding 250 ml of 5% human albumin
      to the pump prime has no effect on postoperative weight gain. The next step could
      be to examine the effect of using larger amounts of albumin or plasma volume
      expanders in the pump prime.

PMID- 11334197
TI  - Is compartment pressure related to plasma colloid osmotic pressure, in patients
      during and after cardiac surgery?
AB  - Haemodilution is always considerable during cardiopulmonary bypass (CPB). If this
      extra fluid sits in the muscle compartments then a corresponding rise in the
      compartment pressure (CP) is to be expected. The aim of this study was to measure
      pressure changes in a body compartment with new equipment, the MTC
      (Microtransducer). Changes in plasma colloid osmotic pressure (COP) were also
      measured during and after CPB to find a connection, if any, between CP and plasma
      COP. Ten elective consecutive CPB patients were studied. A 3-French (3-F)
      catheter-size electronic MTC was inserted in an anterior tibial compartment
      before CPB. The CP was monitored for 48 h. Plasma COP was also measured before,
      during and after CPB. CP increased significantly during and after CPB in all
      patients (p=0.01). COP decreased significantly in all patients (p=0.005), but no
      correlation was found between changes in COP and CP values in this study. Most of
      the patients reached their highest CP just after weaning off bypass. The CP
      remained elevated for 48 h, even though it then tended to decrease again. None of
      the patients reached the starting value within 48 h. COP decreased rapidly after
      going on bypass, but returned towards its starting value approximately 6 h after
      bypass. It is concluded that CP increases considerably during and after CPB and
      stays increased for at least 2 days after CPB. COP decreases during CPB, but
      reaches normal values 6 h after the CPB. No correlation was found between changes
      in CP and COP The MTC is a safe and easy way to measure intracompartment
      pressure.

PMID- 11334198
TI  - Evaluation of a new point of care heparin test for cardiopulmonary bypass: the
      TAS heparin management test.
AB  - Patients undergoing cardiopulmonary bypass (CPB) require anticoagulation with
      heparin to avoid thrombosis within the bypass circuit. The common method used to
      monitor the degree of anticoagulation is the activated clotting time (ACT). We
      evaluated a novel point of care device, the TAS (Pharmanetics, Raleigh, NC, USA)
      heparin management test (HMT), for its suitability in monitoring anticoagulation
      during CPB. In vitro analysis showed a dose-response (r2=0.988) of the HMT from
      0.078-10.0 U/ml heparin, covering the range of heparin used during cardiac
      surgery (2-5 U/ml). Fifty randomly selected patients undergoing CPB were studied.
      Preheparin clotting times for these patients were 143+/-32 s for the HMT and
      146+/-18 s for the ACT; 435+/-60 s HMT and 438+/-39 s ACT during CPB; 145+/-50 s
      HMT and 128+/-14 s ACT post-protamine (r2=0.797). epsilon-Aminocaproic acid
      treatment for inhibition of fibrinolysis did not affect the HMT. We conclude that
      the HMT correlates well with the ACT and may be useful for monitoring heparin
      during CPB. Advantages of the HMT are small sample volume and good sensitivity to
      heparin.

PMID- 11334199
TI  - Transventricular cannulation of the aorta: a useful technique in acute aortic
      dissection.
AB  - A 39-year-old morbidly obese man suffered type-A acute aortic dissection. At
      operation, both external iliac and common femoral arteries were thrombosed.
      Transventricular cannulation of the ascending aorta provided the only means of
      maintaining adequate flow on cardiopulmonary bypass (CPB) to support an unusually
      high body mass index. This method of arterial cannulation for CPB was initially
      described in paediatric patients. We review the application of this technique in
      the adult population.

PMID- 11334200
TI  - Emergency redo mitral valve replacement in a 27-year-old pregnant female with a
      clotted prosthetic mitral valve, preoperative fetal demise and postoperative
      ventricular assist device: a case report.
AB  - A 27-year-old Laotian woman with a St Jude mechanical mitral valve became
      pregnant, requiring a change in her anticoagulant after the first trimester when
      her warfarin sodium (coumadin) was replaced with enoxaparin sodium (lovenox). Her
      prosthetic valve clotted and became dysfunctional. She was 16 weeks pregnant and
      was taken to the operating room for emergency surgery for replacement of the
      valve. The fetus had not been viable for 1-2 weeks, but still remained in utero.
      The clotted valve was replaced with another St Jude valve of a slightly smaller
      diameter (27 mm). The patient could not be weaned from bypass so a right
      ventricular assist device (RVAD) was inserted. The patient was weaned from the
      RVAD after 2 days of support. Two days following removal of the RVAD the fetus
      spontaneously aborted. The patient had a long, complicated hospital course and
      was discharged 3 months later. She subsequently died 4 months after discharge of
      a cerebral hemorrhage from excessive anticoagulation.

PMID- 11334201
TI  - Clinical evaluation of nine hollow-fibre membrane oxygenators.
AB  - In a comparative study we investigated the performance characteristics of nine
      hollow-fibre oxygenators. In a clinical setting, 10 units of each type of
      oxygenator were tested for oxygen exchange, transoxygenator pressure drop, heat
      exchanger performance and blood trauma. The oxygenators included are Maxima PRF
      Plus, Affinity, Forte, Affinity NT, Quantum, Optima, Capiox 1.8, Hilite and
      Quadrox. Ninety patients scheduled for elective coronary bypass surgery were
      enrolled in the study. Cardiotomy suction blood was not allowed to mix with the
      circulating blood. Samples were taken preoperatively (t1), immediately after
      cooling and crossclamping of the aorta (t2), during rewarming (t3), and
      postoperatively (t4). The results showed that under clinical conditions all of
      the tested oxygenators are well capable of meeting the normal and above-normal
      oxygen needs. The Quantum and Affinity NT are the best performing oxygenators
      with respect to oxygen transfer. The Quantum oxygenator with a small membrane
      surface area of 1.9 m2 has also the highest oxygen transfer per square metre. A
      direct relationship between shunt fraction and blood flow could not be
      established in all oxygenators. The lowest shunt fraction at 4 litres blood flow
      was seen in the Maxima, Quantum and Affinity NT groups (15%). At near
      physiological PaO2-values, we noticed a negative influence on the shunt fraction.
      Large differences exist in pressure drop between the oxygenators under
      standardized conditions with circulating priming, as well as during bypass. The
      lowest pressure drop was noticed in the Quadrox and Affinity NT, the highest in
      the Quantum, Capiox and Optima. However, we did not measure any differences in
      pressure drop after cooling and during re-warming. Differences exist between the
      heat exchanger performances. The Quadrox oxygenator is the most efficient, while
      the Maxima has the smallest performance factor. It was not possible to calculate
      heat exchanger performance for the Hilite due to incorrect temperature
      measurement. The high pressure gradients in some of the devices did not result in
      higher haemolysis. Plasma free haemoglobin values were low in each oxygenator.
      There are no differences in platelet drop postoperatively. The influence on blood
      trauma of the higher pressure drop in some of the tested devices, in combination
      with the higher centrifugal pump revolutions needed to overcome this gradient,
      has to be studied with longer perfusion times.

PMID- 11334202
TI  - Systemic leukocyte filtration during cardiopulmonary bypass.
AB  - Cardiopulmonary bypass (CPB) induces a whole body inflammatory response leading
      to postoperative lung dysfunction. Activated leukocytes may play a role in the
      pathogenesis of pulmonary dysfunction. We evaluated postoperative lung function
      after the use of leukocyte-depleting filters incorporated in the extracorporeal
      circuit during CPB. From November 1997 to March 2000, 40 patients underwent
      isolated coronary artery bypass grafting. Patients were randomly allocated to the
      leukocyte-depletion group (group F, 20 patients) or to the control group (group
      C, 20 patients). There was no significant difference between the two groups with
      respect to age, sex, weight, height, body surface area, haemoglobin and
      haematocrit levels, preoperative left ventricular ejection fraction, cooling
      temperature, aortic crossclamping and CBP duration. Blood samples were drawn
      preoperatively, at aortic declamping, 60 min after CPB, after arriving at the
      intensive care unit (ICU) and 24 h after the operation. We analysed blood cell
      count, elastase, interleukin-8 (IL-8) and tumour necrosis factor (TNF-alpha)
      levels and continuous monitoring of arterial blood gases in the intensive care
      unit (ICU). The analysis of total circulating white blood cells (WBCs) showed a
      significant reduction of WBCs in both groups soon after aortic declamping [from
      the right atrium: 6.4 x 10(9)/l +/- 1.4 x 10(9)/l in group F vs 10.3 +/- 1.8 x
      10(9)/l in group C (p<0.05); from the left atrium: 5.8 +/- 1.3 x 10(9)/l in group
      F vs 8.4 +/- 1.9 x 10(9)/l in group C (p<0.05)] and after 60 min of CPB [7.1 +/-
      2.2 x 10(9)/l in group F vs 10.4 +/- 1.8 x 10(9)/l in group C (p<0.05)]. The
      analysis of circulating neutrophils showed similar findings in both groups.
      Elastase levels increased during CPB in both groups with a peak at the end of CPB
      without significant difference between the two groups (group C: 260 +/- 148
      microg/l vs group F: 371 +/- 68 microg/l). The decrease of plasmatic elestase
      levels was observed, for both groups, in the 24 h after CPB. There was no
      difference in intubation time between the two groups (16.4 h for group C vs 11.2
      h for group F). Pulmonary function tested by pulmonary respiratory index [RI =
      partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2 x 100)] did not
      show significant difference between the two groups, either arriving in the ICU
      (group C RI 265 vs group F RI 322), or after 3 h (group RI 304 vs group F RI 305)
      or after 6 h (group C RI 292 vs group F RI 319). Leukocyte-depleting filters
      reduce with blood cells count during CPB, but, in this study, WBC depletion did
      not significantly improve clinical conditions or laboratory finding.

PMID- 11334203
TI  - Hypoxia, reoxygenation and the role of systemic leukodepletion in pediatric heart
      surgery.
AB  - As cardiopulmonary bypass (CPB) in infants and neonates is becoming more
      frequent, the technical performance of these operations for congenital heart
      disease has made significant progress. However, little research has been carried
      out into the conduct of CBP in producing myocardial and pulmonary dysfunction.
      Postoperative organ dysfunction is a problem, particularly for cyanotic infants.
      This paper examines the experimental and clinical experience of injury brought
      about by abrupt reoxygenation of the hypoxic, or cyanotic, heart. The modalities
      of gradual reoxygenation and leukodepletion in limiting this injury are examined,
      leading to the conclusion that injury can be reduced and possibly ameliorated by
      changes in intraoperative management during CBP in children with cyanotic
      disease.

PMID- 11334204
TI  - Timing of leukocyte filtration during cardiopulmonary bypass.
AB  - The effects of leukocyte filtration on the outcome of cardiac surgery with
      cardiopulmonary bypass (CPB) have been shown by numerous investigators. In the
      majority of cases a leukocyte filter is placed in the arterial line instead of a
      standard arterial line filter and used throughout CPB. However, protocols to
      optimize onset and duration of leukocyte filtration have not been sufficiently
      evaluated to date. In this paper, current efforts to improve such protocols are
      demonstrated and discussed. These efforts are based on studies of leukocyte
      pathogenicity during cardiac surgery. A first study (double-blind randomized) was
      performed in routine coronary artery bypass graft (CABG) patients to evaluate
      whether short-term leukocyte filtration during reperfusion by release of the
      aortic crossclamp would reduce reperfusion-associated myocardial damage. Further
      data compare the efficacy of three different filtration concepts to reduce CPB-
      and/or reperfusion-associated leukocyte pathogenicity. Clinical endpoints,
      standard laboratory variables and functional in vitro assays are provided and
      discussed.

PMID- 11334205
TI  - Conditioned blood reperfusion during angioplasty (CoBRA) treatment of acute
      myocardial infarction.
AB  - Acute myocardial infarct (MI) results in ischemia distal to lesions which puts
      heart muscle at risk for reperfusion injury (RI). Neutrophils, platelets and
      complement are putative mediators of RI. Recent advances in filtration technology
      provide integrated neutrophil and platelet removal together with complement
      attenuating properties in a single blood-conditioning device. The present study
      characterizes the properties of a blood-conditioning filter and describes its
      clinical effect when used in conjunction with active hemoperfusion for acute MI.
      The filter reduces leukocytes by 99.9998 +/- 0.0002% (p<0.0001) and platelets by
      99.9934 +/- 0.0069% (p<0.0001). Human plasma, derived from heparinized blood that
      was 'conditioned' by filtration, was studied using the Langendorff isolated
      rabbit heart preparation. The deposition of membrane attack complex and the
      resultant functional myocardial impairments [reflected in hemodynamic and
      biochemical measurements, including developed pressure, coronary blood flow,
      lymph-derived myocardial creatine kinase (CK)] are significantly attenuated by
      blood conditioning. Integration of the blood-conditioning filter into an active
      hemoperfusion system during primary percutaneous transluminal coronary
      angioplasty (PTCA) for acute MI (n=8) did not delay the procedure or cause any
      complications. Reperfusion of occluded coronary arteries with 300 cm3 of
      conditioned blood led to significant improvement in echocardiographic global wall
      motion scores (in standard deviations) following treatment (-1.64 +/- 0.18 to 
      1.45 +/- 0.15, p=0.02). Initial reperfusion of totally occluded coronary arteries
      with conditioned blood leads to acutely improved ventricular function.
      Collectively, these data provide a strong indication for continued investigation
      of conditioned blood reperfusion in angioplasty following acute MI for the long
      term effect upon recovery of salvagable myocardium.

PMID- 11334207
TI  - Filtration of malignant cells: tumour cell depletion in an ex vivo model using a
      leukocyte adhesion filter.
AB  - The clinical use of leukocyte adhesion filters is based on differentiated
      depletion of blood cells, although most of the mechanisms of filtration are still
      unclear. There is also evidence that leukocyte adhesion filters can remove
      disseminated tumour cells from patients' blood. The following proves this
      observation and consists of three parts: in the first part we analysed the
      depletion capacity of the LeucotrapWB filter medium (Pall) in an employed small
      scale model for the cell line HT29 (colorectal origin) in phosphate-buffered
      saline (PBS) solution. A depletion rate of more than 99.6% for HT29 cells was
      seen. In the second part of the study, samples of whole blood were spiked with
      HT29 cells in a similar setting, showing comparable results. In the last part,
      defined cell suspensions of various human primary tumours were admixed to whole
      blood samples and afterwards filtrated in a scale-up model. Again, a nearly
      complete tumour cell reduction was seen after filtration. Results show a
      significant tumour cell reduction and, for most cases, a complete depletion of
      tumour cells independently from quality and origin of the tumour tissue. These
      experiments and further investigation are supposed to help to reduce the risk of
      dissemination of tumour cells in patients undergoing oncological surgery.

PMID- 11334206
TI  - Leukodepletion and aprotinin improve clinical outcome after extracorporeal
      circulation.
AB  - Most cardiac operations involve the use of extracorporeal circulation with its
      attendant systemic inflammatory response syndrome. Many anti-inflammatory
      strategies hold promise for reducing the associated morbidity of cardiopulmonary
      bypass. The application of pharmacological and mechanical strategies to control
      this inflammatory response now has demonstrable clinical benefit. The additional
      costs of these successful strategies are offset by the economic savings and
      improved quality of care.

PMID- 11334208
TI  - Effects of leukocyte depletion of blood transfusions on postoperative
      complications.
AB  - Postoperative complications associated with blood transfusions are frequently
      reported to be a result of the transfused leukocytes. This paper examines the
      effects of leukocyte depletion. Leukocyte depletion by filtration which can
      reduce leukocyte presence by more than 99.9%. The implications of this are
      postulated in terms of the results that may be obtained.

PMID- 11334209
TI  - Cell salvage and leucodepletion.
AB  - Cell salvage has been used as a method of blood conservation for more than three
      decades. Although the principles and development of the Latham bowl had occurred
      in the 1960s, it was not until the early 1970s that washing of the concentrated
      red cells was introduced and a product that was universally acceptable was
      obtained. The last 25 years have seen little in the way of development of cell
      salvage, although significant refinement has taken place. Although the simple
      picture of cell salvage involves removal of the buffy coat, including platelets
      and leucocytes, in practice there are reports of great variation in the removal
      of these cells. Most recent studies suggest that there is very little removal of
      leucocytes by cell salvage. The leucocytes that remain in the red cell suspension
      following cell salvage have undergone significant morphological changes and the
      surface expression of leucocyte adhesion receptors increases dramatically during
      the process. There is little evidence that removal of these activated leucocytes
      has any significant clinical benefit. Although leucofiltration of blood before
      storage has been shown to be an extremely safe process, 'bedside
      leucofiltration', including leucofiltration of cell salvage blood, may not be
      without problems. Reports of hypotensive events while receiving blood products
      through a bedside leucocyte reduction filter have emerged during the last few
      years. This may be due to bradykinin production following platelet exposure to
      negatively charged leucocyte filters.

PMID- 11334210
TI  - The effects of leucodepletion in patients who develop the systemic inflammatory
      response syndrome following cardiopulmonary bypass.
AB  - The development of the systemic inflammatory response syndrome (SIRS) is
      associated with increased morbidity and mortality. Numerous anticytokine trials
      have failed to demonstrate any outcome benefit and there has been little evidence
      of improvement in the prognosis of this condition over the past 20 years. This
      study examines the effect of using a white cell filter designed to remove
      polymorphonuclear cells (PMNs) in patients who developed SIRS 36 h after
      cardiopulmonary bypass (CPB). Twenty-four patients were randomized to receive
      either leucofiltration (LF) or control therapy (CT). The two groups were well
      matched at study entry in terms of age, severity of illness and length of time on
      CPB. LF patients received 60 min filtration periods using a venovenous
      extracorporeal circuit at a flow rate of 200 ml/min with the cycle repeated every
      12 h while SIRS and other entry criteria were met. CT patients received standard
      therapy. LF patients received an average of 4.2 cycles (range 1-8) and, after 15
      min filtration, the total leucocyte count had fallen from 16.2 +/- 5.3 to 10.4 +/
      3.3 x 10(9)/l and PMN from 14.4 +/- 5.2 to 8.3 +/- 4.2 x 10(9)/l. The mean
      platelet count changed from 127 +/- 87 to 117 +/- 82 x 10(9)/l. No adverse
      effects related to leucodepletion were observed. There was no difference between
      the groups in either mortality or length of stay at the intensive care unit or at
      hospital discharge. Organ function was assessed regularly during the study period
      and significant changes occurred only in respiratory and renal function. In the
      LF patients, respiratory function assessed by change in hypoxaemia index from
      baseline and renal function assessed by serum creatinine showed significant
      treatment effects compared to CT patients (p < 0.01, < 0.01 respectively); three
      CT patients, but no LF patients, received haemofiltration during the study
      period. Leucofiltration safely and effectively removes circulating PMNs from
      patients with SIRS following CPB. This may result in improved pulmonary and renal
      function in these patients. Further studies are required of the kinetics and
      phenotypic characteristics of PMN removal by leucofiltration and a larger
      multicentre study will be necessary to determine whether this novel therapy has a
      significant outcome benefit in critically ill patients with SIRS.

PMID- 11334211
TI  - Leucodepletion and the interaction of polymorphonuclear cells with endothelium in
      systemic inflammatory response syndrome.
AB  - The abnormal interaction of polymorphonuclear cells (PMNs) with blood vessel
      walls is considered to underlie the multiple organ failure of systemic
      inflammatory response syndrome (SIRS). This consideration is supported by the
      present finding that PMNs from patients with SIRS are activated, as assessed by
      an increased distribution of cells bearing CD64, enhanced expression of CD11b and
      decreased expression of CD62L, and are highly adhesive to endothelial monolayers.
      Passage of SIRS blood through leucodepletion filters in a laboratory-designed
      extracorporeal circuit resulted in a marked depletion of PMNs. Of the PMNs that
      remained in the blood, far fewer cells bound to cultured endothelial cells in
      comparison with PMNs prior to leucofiltration. We propose that leucofiltration of
      SIRS blood will limit the number of PMNs available for binding to blood vessel
      walls and, hence, reduce the pathological manifestations associated with this
      disorder.

PMID- 11334212
TI  - Comprehension of signs by dolphins (Tursiops truncatus).
AB  - The authors assessed the ability of 6 captive dolphins (Tursiops truncatus) to
      comprehend without explicit training 3 human communicative signs (pointing,
      directed gaze, and replica). Pointing consisted of indicating the target item
      with the index finger and a fully extended arm. Directed gaze consisted of
      orienting the head and eyes toward the target item while the rest of the body
      remained stationary. The replica signal consisted of holding up an exact
      duplicate of the target item. On the initial series of 12 trials for each
      condition, 3 dolphins performed above chance on pointing, 2 on gaze, and none for
      replica. With additional trials, above chance performance increased to 4 dolphins
      for pointing, 6 for gazing, and 2 for replica. The replica sign seemed to be the
      most taxing for them (only 2 dolphins achieved results significantly above
      chance). Taken together, these results indicate that dolphins are able to
      interpret untrained communicative signs successfully.

PMID- 11334213
TI  - Size matters: impact of item size and quantity on array choice by chimpanzees
      (Pan troglodytes).
AB  - The authors previously reported that chimpanzees (Pan troglodytes) showed a
      striking bias to select the larger of 2 candy arrays, despite a reversed reward
      contingency in which the animals received the smaller, nonselected array as a
      reward, except when Arabic numerals were used as stimuli. A perceptual or
      incentive-based interference occurred that was overcome by symbolic stimuli. The
      authors of the present study examined the impact of element size in choice
      arrays, using 1 to 5 large and small candies. Five test-sophisticated chimpanzees
      selected an array from the 2 presented during each trial. Their responses were
      not optimal, as animals generally selected arrays with larger total mass; thus,
      they received the smaller remaining array as a reward. When choice stimuli
      differed in size and quantity, element size was more heavily weighted, although
      choices reflected total candy mass. These results replicate previous findings
      showing chimpanzees' difficulties with quantity judgments under reverse reward
      contingencies and also show that individual item size exerts a more powerful
      interference effect.

PMID- 11334214
TI  - Food stealing by young Norway rats (Rattus norvegicus).
AB  - Six experiments were undertaken to explore factors affecting young rats' (Rattus
      norvegicus) frequencies of stealing food from conspecifics when identical food is
      available in surplus. It was found that (a) rats would walk across a bed of
      pellets to steal the particular pellet a peer was eating, (b) frequency of
      stealing within a pair did not decrease over days, (c) rats stole unfamiliar
      foods more frequently than familiar foods, (d) younger rats stole from older rats
      more frequently than older rats stole from younger ones, (e) hungry rats stole
      more frequently than replete rats, and (f) rats that had stolen a pellet of
      unfamiliar food from an anesthetized conspecific subsequently exhibited an
      enhanced preference for that food. Results suggest that food stealing is a mode
      of active seeking of information about what foods to eat.

PMID- 11334215
TI  - Individual differences in response to a stranger: social impulsivity as a
      dimension of temperament in vervet monkeys (Cercopithecus aethiops sabaeus).
AB  - Social impulsivity in response to a stranger was assessed in male vervet monkeys
      (Cercopithecus aethiops sabaeus) using the Intruder Challenge Test. Vervets (N =
      128, ages 3-18 years) were presented with an unfamiliar adult male at the
      periphery of the home enclosure. An index of impulsivity reflecting variation in
      the tendency to rapidly approach, engage, and challenge the intruder was derived
      from factor analysis of behavioral responses. Scale reliability (alpha = .84) and
      test-retest consistency (intraclass correlation = .83) were high, indicating that
      this index reliably and efficiently measures a stable aspect of temperament from
      impulsive to inhibited. Impulsivity scores peaked at age 4, when vervet males
      typically emigrate from the natal group. The highest ranking males in each group
      were more likely to score in the moderate range, whereas lower ranking males were
      more likely to score in the highest (impulsive) or lowest (inhibited) quartiles.

PMID- 11334216
TI  - Do big-brained animals play more? Comparative analyses of play and relative brain
      size in mammals.
AB  - It has been hypothesized that play is more likely to be present in larger brained
      species. We tested this hypothesis in mammals using independent contrasts, a
      method that controls for phylogenetic relatedness. Comparisons across 15 orders
      revealed that the prevalence and complexity of play was significantly correlated
      with brain size, with larger brained orders having more playful species. Three
      orders, Rodentia, Marsupialia, and Primates, were used for within-order
      comparisons among species and, where possible, among families. The comparisons
      were not significant for rodents or primates, and those for marsupials yielded
      inconsistent results. Therefore, although a strong relationship is present at the
      highest taxonomic level of comparison, it diminishes or evaporates at lower level
      comparisons.

PMID- 11334217
TI  - Menstrual-cycle synchrony: problems and new directions for research.
AB  - Since M. K. McClintock (1971) published the 1st study on menstrual synchrony
      among women, a number of other studies have also reported synchrony using a
      variety of methods. The most recent reports of synchrony come from A. Weller, L.
      Weller, and colleagues, and their findings of synchrony have been getting
      stronger (by their own account). In this article, the author analyzes their new
      methodology and presents 2 simulation studies that demonstrate how biases and
      errors can produce synchrony as an artifact. Two mutually reinforcing categories
      of errors are identified: (a) errors in calculating the expected mean onset
      difference between cycles when there is cycle variability and (b) errors that may
      result from allowing participants to fill out menstrual-cycle-onset calendars,
      including recall biases and the mutual exchange of information. It is suggested
      that synchrony may be a biological state to be avoided and that cycle variability
      may facilitate female mate choice.

PMID- 11334218
TI  - Same-different conceptualization by baboons (Papio papio): the role of entropy.
AB  - The authors trained 6 baboons (Papio papio) to make 1 of 2 report responses 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, the baboons discriminated the
      same arrays from the different arrays, and they transferred their discriminative
      responding to arrays of novel icons. In Experiments 2 and 3, the baboons
      exhibited strong sensitivity to the degree of display variability when they were
      shown mixed arrays that comprised some same and some different items. The
      information theoretic measure "entropy" systematically described these results
      and outperformed several rival metrics. Finally, in Experiments 4 and 5, the
      baboons' responses to displays that contained jittered and blurred icons
      suggested that their same-different conceptual behavior was not based on the
      spatial orderliness of the visual arrays.

PMID- 11334219
TI  - Social influences on parental and nonparental responses toward pups in virgin
      female prairie voles (Microtus ochrogaster).
AB  - Pair-bonded prairie voles (Microtus ochrogaster) are biparental after the birth
      of pups. However, whereas most adult virgin males are parental, most virgin
      females are not. In 6 experiments, influences on the parental behavior of virgin
      female prairie voles were examined. It was found that (a) young virgin females
      were more maternal than older females, (b) the postweaning sex ratio of cage
      mates did not affect females' responses to pups, (c) females raised to adulthood
      with their parents and younger siblings present were highly parental, (d) 48-hr
      exposure to pups beginning at weaning increased some aspects of later maternal
      responding, (e) rearing to adulthood with the parents even in the absence of
      younger siblings also increased females' maternal responding, and (f) the
      increase was seen only if both parents were present. Continued parental presence
      promotes alloparental behavior, possibly important if daughters do not disperse
      from the natal nest.

PMID- 11334220
TI  - Imitative learning in Japanese quail (Coturnix japonica) depends on the
      motivational state of the observer quail at the time of observation.
AB  - The 2-action method was used to examine whether imitative learning in Japanese
      quail (Coturnix japonica) depends on the motivational state of the observer quail
      at the time of observation of the demonstrated behavior. Two groups of observers
      were fed before observation (satiated groups), whereas 2 other groups of
      observers were deprived of food before observation (hungry groups). Quail were
      tested either immediately following observation or after a 30-min delay. Results
      indicated that quail in the hungry groups imitated, whereas those in the satiated
      groups did not, regardless of whether their test was immediate or delayed. The
      results suggest that observer quail may not learn (through observation) behavior
      that leads to a reinforcer for which they are unmotivated at the time of test. In
      addition, the results show that quail are able to delay the performance of a
      response acquired through observation (i.e., they show deferred imitation).

PMID- 11334221
TI  - Habituation as a mechanism of reduced aggression between neighboring territorial
      male bullfrogs (Rana catesbeiana).
AB  - Territorial animals often exhibit relatively lower levels of aggression toward
      familiar territorial neighbors than toward strangers. Habituation to a neighbor
      or its communication signals has been proposed to account for this reduced
      aggression between adjacent territorial neighbors. The authors asked whether
      discrimination between neighbors and strangers by territorial male bullfrogs
      (Rana catesbeiana) could result from habituation of the aggressive response to
      repeated presentations of the acoustic communication signals of a simulated new
      neighbor calling from an adjacent territory. In 3 field playback experiments, the
      authors found evidence for 5 response characteristics that operationally define
      habituation. Moreover, aggressive response decrements persisted between nights of
      chorusing and were specific to an individually distinct property of male
      advertisement calls. The authors suggest that reduced aggression between
      neighboring territorial male bullfrogs could result from long-term, stimulus
      specific habituation to the advertisement calls of a new neighbor.

PMID- 11334222
TI  - Pigeons (Columba livia) learn to link numerosities with symbols.
AB  - After responding to each element in varying, successive numerosity displays,
      pigeons (Columba livia) had to choose, out of an array of symbols, the symbol
      designated to correspond to the preceding number of elements. After extensive
      training, 5 pigeons responded with significant accuracy to the numerosities 1 to
      4, and 2 pigeons to the numerosities 1 to 5. Several tests showed that feedback
      tones accompanying element pecks, the familiarity of element configurations, and
      the shape of the elements were not crucial to this performance. One test,
      however, indicated that the number of pecks issued to the elements was important
      for numerosities above 2. An additional test confirmed that the birds chose the
      symbol that corresponded to a particular numerosity rather than the positions
      that the symbols had held during training.

PMID- 11334223
TI  - Human (Homo sapiens) facial attractiveness in relation to skin texture and color.
AB  - The notion that surface texture may provide important information about the
      geometry of visible surfaces has attracted considerable attention for a long
      time. The present study shows that skin texture plays a significant role in the
      judgment of female facial beauty. Following research in clinical dermatology, the
      authors developed a computer program that implemented an algorithm based on co
      occurrence matrices for the analysis of facial skin texture. Homogeneity and
      contrast features as well as color parameters were extracted out of stimulus
      faces. Attractiveness ratings of the images made by male participants relate
      positively to parameters of skin homogeneity. The authors propose that skin
      texture is a cue to fertility and health. In contrast to some previous studies,
      the authors found that dark skin, not light skin, was rated as most attractive.

PMID- 11334224
TI  - Antidepressant drugs attenuate 7-OH-DPAT-induced hypoactivity in rats.
AB  - Various antidepressant drugs given repeatedly induce the supersensitivity of
      postsynaptic dopamine D2 and D3 receptors. Several reports have also suggested
      the subsensitivity of presynaptic dopamine D2 receptors. The aim of the present
      study was to investigate the effect of two antidepressant drugs with different
      pharmacological profile, i.e. imipramine and citalopram, administered repeatedly,
      on the hypoactivity induced by low dose (0.05 mg/kg sc) of (+/-)7-hydroxy
      dipropylaminotetralin (7-OH-DPAT), a dopamine D3 receptor preferring agonist.
      Male Wistar rats were treated with antidepressant drugs (10 mg/kg po) either
      acutely (single dose) or repeatedly (twice daily for 14 days). Two or 24 h after
      the last dose of antidepressant drug, the locomotor activity induced by (+/-)7-OH
      DPAT was measured in photoresistor actometers. Additionally, the influence of
      nafadotride (0.2 or 1 mg/kg ip), a dopamine D3 preferring antagonist, on the (+/
      )7-OH-DPAT-induced changes in locomotor activity was studied. Low dose of (+/-)7
      OH-DPAT induced the locomotor hypoactivity, however, this effect was not
      modulated by nafadotride. Antidepressant drugs given repeatedly, but not acutely,
      reversed the effect of (+/-)7-OH-DPAT, and this effect of antidepressants was
      antagonized by nafadotride. The obtained results indicate that the sensitivity of
      dopamine D3 receptors might be altered by the repeated treatment with
      antidepressant drugs.

PMID- 11334225
TI  - Influence of antiepileptics on efficacy of antidepressant drugs in forced
      swimming test.
AB  - Antidepressant medications are indicated in a variety of sustained mood
      disorders, including depression, and in epileptic patients. On the other hand,
      some antiepileptics are also used in the treatment of affective disorders.
      Therefore, some interactions may appear between antiepileptics and antidepressant
      drugs. The aim of the present study was to investigate the influence of the
      treatment with antiepileptic drugs on the antidepressants' activity in mice
      (forced swimming test or assessment of locomotor activity). The animals received
      intraperitoneally (ip) antiepileptics: phenytoin (PHT) at 6 or 12 mg/kg,
      valproate (VAL) at 50, 100, 200 or 300 mg/kg, carbamazepine (CBZ) at 4, 6 or 9
      mg/kg, vigabatrin (VGB) at 50, 100, 200 or 300 mg/kg or lamotrigine (LTG) at 12.5
      or 25 mg/kg, 30, 60 or 90 min before the injection of antidepressants: imipramine
      (IMI, 20 mg/kg) amitriptyline (AMI, 10 mg/kg), maprotiline (MAP, 10 mg/kg),
      mianserin (MIA, 15 mg/kg), fluoxetine (FLX, 40 mg/kg) or fluvoxamine (FLV, 20
      mg/kg). It was shown that the acute administration of antidepressant drugs
      significantly reduced the immobility time in forced swimming test in mice.
      Antiepileptics, given in a single dose, caused did not change the behavior of
      mice in this test, however, they abolished the characteristic effect of
      antidepressant drugs. Each antidepressant, given at a single dose, shortening the
      immobility time in forced swimming test and reduced the locomotor activity of
      mice. This sedative effect of antidepressants was intensified by antiepileptics.
      The present results suggest that antiepileptics can reduce the activating effect
      of antidepressant drugs of different groups.

PMID- 11334226
TI  - Two essential amino acids, L-lysine and L-histidine, in five types of
      experimental seizures.
AB  - L-Lysine (250-2,000 mg/kg) and L-histidine (1,000-2,000 mg/kg) significantly
      raised the electroconvulsive threshold. D-Histidine (1,000 mg/kg) was completely
      ineffective in this regard. Both amino acids were generally inactive in
      pentetrazole-, picrotoxin- and aminophylline-induced seizures, though L-histidine
      (2,500 mg/kg) significantly reduced the number of mice with clonic convulsions in
      the pentetrazole test. Also, L-lysine (2,500 and 3,000 mg/kg) significantly
      diminished mortality rate in aminophylline-induced seizures. In addition, L
      lysine (2,500-3,000 mg/kg) and L-histidine (2,000-2,500 mg/kg) delayed the onset
      of aminophylline- and picrotoxin-evoked convulsions. L-Lysine and L-histidine
      (both up to 1,000 mg/kg) did not affect amygdala-kindled seizures in rats. The
      results indicate that some of indispensable amino acids may play a role in the
      inhibitory transmission in the central nervous system. A possibility arises that
      appropriate diet may be an important supportive factor in the treatment of some
      epileptic patients, probably suffering from generalized tonic-clonic seizures.

PMID- 11334227
TI  - Possible involvement of mGluR1 together with group II and III mGluRs in ibotenate
      stimulated cAMP formation in the rat brain cortical slices.
AB  - The mechanism of adenylyl cyclase activation by the stimulation of metabotropic
      glutamate receptors (mGluRs) is still unknown. Our previous studies have shown
      that mGluR agonist, ibotenic acid, produced a significant increase in cAMP
      accumulation. The aim of the present studies was to investigate the mechanism of
      ibotenate-stimulated cAMP formation in cortical slices of adult rats. Antagonists
      of all groups of mGluRs were examined to establish their effects on the
      stimulation of cAMP production by ibotenic acid. The obtained results indicate
      that ibotenate-stimulated cAMP accumulation in the rat brain cortical slices
      depends on the activation of mGluR1, but not on mGluR5. Moreover, activation of
      group II and group III mGluRs also influences ibotenate-stimulated cAMP
      formation.

PMID- 11334228
TI  - Effects of some centrally active drugs on the allopregnanolone synthesis in rat
      brain.
AB  - Effects of antidepressants (desipramine, amitriptyline), anticonvulsants
      (phenytoin, diazepam, carbamazepine) and addictive drugs (amphetamine, morphine),
      used at a concentration of 100 microM on the conversion of [14C]-progesterone to
      5alpha-pregnane-3,20-dione and allopregnanolone in slices of the frontal cortex
      and olfactory bulb from rat brain were studied. The synthesis of 5alpha-pregnane
      3,20-dione and allopregnanolone was stronger in the olfactory bulb than in the
      frontal cortex. The biosynthesis of allopregnanolone in the frontal cortex was
      higher by 74, 109 and 187% when stimulated by amitriptyline, desipramine and
      carbamazepine, respectively, and, to a lesser degree, by phenytoin and morphine.
      Desipramine and morphine decreased the concentration of 5alpha-pregnane-3,20
      dione. In the olfactory bulb, only carbamazepine enhanced allopregnanolone
      production, but none of the tested drugs had any effect on 5alpha-pregnane-3,20
      dione synthesis. It is concluded that some psychotropic drugs may increase
      allopregnanolone synthesis by stimulating the activity of the enzyme, 3alpha
      hydroxysteroid dehydrogenase, in the frontal cortex, and that this neurosteroid
      may be partly involved in the mechanism of action of the drugs under study.

PMID- 11334229
TI  - Influence of nitric oxide on the cardiovascular action of secretin in intact
      rats. Part A. Does nitric oxide influence the effect of secretin on arterial
      blood pressure?
AB  - The present study aimed to determine the influence of nitric oxide (NO) on the
      action of secretin in the cardiovascular system in intact rats. The studies
      involved the in vivo measurements of the systolic (SBP) and diastolic (DBP) blood
      pressure. The measurements were conducted when NO was absent, which was attained
      by the use of NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME),
      and when NO was in excess which was obtained by the administration of L-arginine
      (L-arg), the substrate for NO synthase or exogenous donor of NO, sodium
      nitroprusside (SNP). Secretin given at the following three doses: 0.75, 1.5 and
      3.0 micromoles/kg iv increased SBP and DBP. L-NAME inhibited the slight
      hypertensive effect of secretin. L-arg abolished the hypertensive effect of the
      peptide given at the smallest dose, did not change the effect of secretin
      administered at the medium dose (which did not raise the pressure) and preserved
      the action of the highest secretin dose. SNP abolished the hypertensive effect of
      all doses of the peptide. In conclusion, the study has shown that both the lack
      and excess of NO change the in vivo effect of secretin in intact rats.

PMID- 11334230
TI  - Influence of nitric oxide on the cardiovascular action of secretin in intact
      rats. Part B. Does nitric oxide influence the effect of secretin on isolated
      heart function?
AB  - The present study was designed to examine the effect of absence or excess of NO
      on secretin-mediated responses in the isolated heart. This problem was
      investigated using the modified Langendorff's method. Secretin administered at
      two higher doses increased the cardiac contraction amplitude (p < 0.05), but did
      not change the heart rate and coronary outflow. NO was depleted from experimental
      system by perfusion of the isolated heart with NO synthase inhibitor L-NAME (NG
      nitro-L-arginine methyl ester) at 10 microM. It caused a significant decrease in
      coronary outflow (p < 0.01) and the tendency to bradycardia (p > 0.05) with no
      change in cardiac contraction amplitude. L-NAME abolished the positive inotropic
      effect of the medium secretin dose and preserved the inotropic effect of the
      highest dose of the peptide. It reversed the tendency to decrease coronary
      outflow induced by secretin (and L-NAME) given separately. To study the effect of
      NO excess, we applied the substrate for NO synthesis, amino acid L-arginine (L
      arg) (100 microM) or exogenous donor of NO--sodium nitroprusside (SNP) (100
      microM). Both substances did not affect the isolated heart function. L-arg did
      not change the effect of secretin, however it abolished non significant decrease
      in coronary outflow evoked by the highest dose of secretin. SNP preserved the
      positive inotropic action of the peptide and expressively reversed the negative
      values of coronary outflow observed after its co-administration with the highest
      dose of secretin. These results indicate that both the absence and excess of NO
      change the cardiac effect of secretin in the same direction.

PMID- 11334232
TI  - Inter- and intra-individual variability of ethanol pharmacokinetics over a long
      period of time.
AB  - In most research, the inter- and intra-individual variability of time profiles of
      ethanol concentration has been studied over a relatively short period of time. We
      present a study of inter- and intra-individual variability of ethanol
      pharmacokinetics in five healthy volunteers (social drinkers) over a period of
      around eight years. The volunteers received a dose of 0.7 g/kg (men) and 0.6 g/kg
      (women) of ethanol in the form of vodka diluted with mineral water. The blood
      ethanol concentrations in a series of samples were measured by gas
      chromatography. For pharmacokinetic calculations, a model with first-order
      absorption and Michaelis-Menten elimination was applied. A linear regression
      technique was used to calculate Widmark's coefficient. The area under the
      concentration-time curve (AUC) was calculated by trapezoid rule. A tendency for
      pharmacokinetic parameters to alter during the study time was observed, however,
      these changes were random and did not correlate with the duration of the study.
      The highest inter- and intra-subject variability of the half time of absorption
      was observed. The maximal elimination velocity and Michaelis-Menten constant were
      also very unstable; coefficients of variation were 55.8% and 79.0%, respectively.
      Other calculated pharmacokinetic parameters (AUC, beta60, V/F, Cmax) were
      characterized by a lower variability with a coefficient of variation around 36%.
      Back extrapolation of plasma ethanol concentration using mean value of beta60 for
      each subject showed that results could be underestimated up to 26% or
      overestimated up to 102%.

PMID- 11334231
TI  - Different mechanisms of positive chronotropic actions of isoprenaline and
      noradrenaline on isolated guinea pig right atria revealed by pretreatment with
      rilmakalim.
AB  - In this study we tested the influence of activation of ATP-sensitive K+ channels
      (KATP) on the changes in automatism induced by isoprenaline, noradrenaline and
      phenylephrine. Experiments were performed on the spontaneously beating right
      atria isolated from guinea pig. The rate of spontaneously beating preparations
      was measured under different experimental conditions. Rilmakalim (formerly HOE
      234) was used as an activator of KATP channels. Isoprenaline induced significant,
      concentration-dependent positive inotropic action. This effect was strongly
      attenuated only in the presence of selective blockers of beta1- (metoprolol), but
      not beta2-adrenoceptor subtype (ICI 11855). Pretreatment with 4 microM rilmakalim
      resulted in a significant increase in the described effects of isoprenaline on
      automatism of isolated right atria. Phenylephrine (1 to 100 microM) in the
      presence of 1 microM propranolol, did not cause any changes in automatism of
      guinea pig right atria. Slight but significant positive chronotropic action
      induced by noradrenaline at lower concentrations (0.1 to 10 microM) in the
      presence of 1 microM propranolol was significantly decreased by pretreatment with
      rilmakalim. However, the effects obtained at higher concentrations (30 and 100
      microM) of noradrenaline were enhanced. Interactions mentioned above were
      prevented by addition of 3 microM glibenclamide. The results imply that positive
      chronotropic effect of noradrenaline in the presence of propranolol is mediated
      by adrenoceptor subtype different from alpha1-, beta1- and beta2-adrenoceptors.

PMID- 11334233
TI  - An opioid receptor antagonist, naltrexone, does not alter taste and smell
      responses in humans.
AB  - Several studies have shown that an opioid receptor antagonist, naltrexone,
      decreases palatable food consumption. Naltrexone has also been reported to reduce
      ethanol intake in alcohol-preferring rodents and human alcoholics. The aim of the
      present study was to assess the effects of naltrexone on taste and smell
      responses in healthy male volunteers. Naltrexone did not alter intensity and
      pleasantness of sucrose, quinine, citric acid, sodium chloride, and ethanol
      taste. Similarly, ratings of olfactory stimuli (orange extract and ethanol) and
      Coca-Cola flavor were not influenced by the opioid antagonist. Our findings may
      indicate that: (i) naltrexone exerts marginal, if any, effects on gustatory and
      olfactory responses in humans; (ii) the drug does not alter orosensory responses
      to ethanol.

PMID- 11334234
TI  - Zinc exhibits an antidepressant-like effect in the forced swimming test in mice.
AB  - The effects of zinc, the NMDA receptor inhibitor, were studied in the forced
      swimming (Porsolt's) test in mice. Zinc (ZnSO4) at a dose of 30 mg/kg (but not at
      a dose of 10 mg/kg), similarly to imipramine (30 mg/kg), reduced the immobility
      time in that test. Moreover, zinc at both doses reduced the locomotor activity.
      The obtained results indicate that zinc induces an antidepressant-like effect in
      the forced swimming test. Since zinc reduces the locomotor activity, this
      antidepressant-like effect is not related to the alteration of general activity.

PMID- 11334235
TI  - Effects of corticosterone and its synthesis blockade on the cocaine-induced
      discriminative stimulus effects in rats.
AB  - Several studies have argued that the hypothalamo-pituitary-adrenal (HPA) axis is
      of significance to behavioral effects evoked by drugs of abuse (e.g. cocaine).
      The role of the HPA axis in the subjective effects of cocaine was investigated in
      rats trained to discriminate cocaine (10 mg/kg, ip, -15 min) from saline (ip, -15
      min) in a two-choice, water-reinforced fixed ratio (FR) 20 drug discrimination
      paradigm. In substitution tests, neither the exposure to a novel environment nor
      the social defeat stress, applied to rats after a dose of cocaine (2.5 mg/kg)
      which induced a ca. 42% drug-appropriate responding, influenced cocaine
      discrimination. Given alone, corticosterone (20 and 40 mg/kg, sc, -60 min)
      elicited a ca. 7% drug-appropriate responding. Combined injections of
      corticosterone and cocaine (0.625-5 mg/kg) did not affect the dose-response curve
      for cocaine. Surgical adrenalectomy did not modify the effects of cocaine; using
      a cumulative dosing procedure in the drug discrimination paradigm we found, that
      the dose-response curves for cocaine in adrenalectomized rats and sham-operated
      controls practically did not differ. Ketoconazole (an inhibitor of
      adrenocorticosteroid synthesis; 50 mg/kg, ip) given acutely (60 min) did not
      affect cocaine discrimination. Given subacutely (24, 16 and 1 h before tests),
      ketoconazole (50 mg/kg) produced a left-ward shift in the dose-response curve for
      cocaine and decreased its ED50 value. Another inhibitor of corticosterone
      secretion, metyrapone (50 mg/kg, sc), given acutely (120 min) did not affect the
      dose-response curve for cocaine. However, repeated injections (24, 16 and 2 h
      before tests) of metyrapone (50 mg/kg) with different doses of cocaine resulted
      in a rightward shift in the dose-response curve for cocaine and an increase in
      its ED50 value. The obtained results seem to exclude any role of the HPA axis in
      mediating subjective effects of cocaine, since neither corticosterone and stress
      nor adrenalectomy modified the discriminative stimulus effects of cocaine in
      rats. The reduction and potentiation of cocaine discrimination following subacute
      metyrapone and ketoconazole, respectively, may depend on changes in the levels of
      intermediate neurosteroids "upstream" from corticosterone in its biosynthesis
      pathway.

PMID- 11334236
TI  - Influence of adenosine receptor agonists and antagonists on amphetamine-induced
      stereotypy in rats.
AB  - The influence of adenosine receptor agonists and antagonists on amphetamine
      induced stereotypy was examined in male Wistar rats. Adenosine A2 receptor
      agonists CGS 21680 (0.5-2 mg/kg ip) and a non-specific A2/A1 receptor agonist
      NECA (0.05-0.1 mg/kg ip) attenuated in a dose dependent manner amphetamine
      induced stereotypy (2 mg/kg sc). CPA as specific agonist of adenosine A1
      receptors counteracted this stereotypy, but only in a narrow range of doses (0.1
      0.2 mg/kg ip). Adenosine A2A receptor antagonist, DMPX (3 and 6 mg/kg ip)
      potentiated stereotypy induced by either subthreshold dose of amphetamine 0.5
      mg/kg or a high one 2 mg/kg. A non-selective adenosine receptor antagonist,
      caffeine (10 mg/kg ip) potentiated effect of low dose of amphetamine, but only in
      a dose of 20 mg/kg ip increased stereotypy induced by 2 mg/kg ip of amphetamine.
      A selective adenosine A1 receptor antagonist CPT (1 and 3 mg/kg ip) was
      ineffective in reversing amphetamine-induced stereotypy. These results confirm
      the existence of adenosine-dopamine interactions in the brain, and the
      suggestions that A2 adenosine receptor agonists may have antipsychotic
      properties.

PMID- 11334237
TI  - Effect of acute and chronic administration of citalopram on glutamate and
      aspartate release in the rat prefrontal cortex.
AB  - The present study was designed to determine whether peripheral administration of
      the selective serotonin reuptake inhibitor (SSRI) citalopram influenced glutamate
      and aspartate release in the rat prefrontal cortex using in vivo microdialysis.
      Citalopram was given acutely at doses of 10 and 20 mg/kg or chronically at a dose
      of 10 mg/kg daily for two weeks, in both cases by intraperitoneal (ip) route.
      Citalopram given at a single dose of 20 mg/kg, but not 10 mg/kg, significantly
      inhibited release of glutamate and aspartate induced by sodium channel activator,
      veratridine (100 microM). Glutamate and aspartate release was also diminished in
      animals treated chronically with citalopram. Citalopram did not affect
      extracellular level of 5-hydroxytryptamine (5-HT) after acute doses, but
      increased it after chronic administration. On the other hand, single and repeated
      doses of the drug inhibited veratridine-evoked 5-HT release. Neither single nor
      chronic treatment with citalopram influenced spontaneous and evoked dopamine (DA)
      release. The results suggest that in the presence of depolarizing agent, e.g.
      under conditions resembling a disturbed homeostasis of neuronal network,
      antidepressant drugs with profile of SSRI may influence excitatory systems in the
      brain. This effect does not seem to be dependent on the interaction with 5-HT or
      DA neurotransmission, but rather some inhibitory modulators stimulated in stress
      situations may contribute to the observed results.

PMID- 11334238
TI  - Distribution interactions between perazine and antidepressant drugs. In vivo
      studies.
AB  - Perazine belongs to the most frequently chosen neuroleptics for a combination
      with antidepressants in the therapy of complex or "treatment-resistant"
      psychiatric illnesses. The aim of the present study was to investigate the effect
      of the distribution interaction between perazine and antidepressants in vivo.
      Experiments were carried out on male Wistar rats. Animals received perazine and
      an antidepressant drug (imipramine or fluoxetine), separately or jointly, at a
      dose of 10 mg/kg ip. Concentrations of perazine, imipramine, fluoxetine and their
      metabolites in the blood plasma and tissues were measured at 1 h after
      administration of the drugs (HPLC). Effects of distribution interactions were
      estimated on the basis of the calculated tissue/plasma and lysosome-poor/lysosome
      rich tissue concentration ratios, considering the heart and muscles as lysosome
      poor and the lungs, liver and kidneys as lysosome-rich ones. Both imipramine and
      fluoxetine diminished the tissue/plasma concentration ratios of perazine for the
      lungs and kidneys (not for the liver), but elevated those ratios for the brain,
      muscles and heart. On the other hand, perazine lowered the lungs/plasma
      concentration ratio of both antidepressants and the liver/plasma concentration
      ratio of imipramine. Simultaneously, perazine elevated the brain/plasma and
      heart/plasma concentration ratios of both antidepressants. Consequently, the
      perazine concentration ratios of lysosome-poor/lysosome-rich tissue significantly
      increased in the presence of the investigated antidepressants, with an exception
      of the muscles/liver concentration ratio. At the same time, perazine raised the
      heart/lysosome-rich tissue concentration ratios of imipramine and fluoxetine, not
      changing significantly the muscles/lysosome-rich concentration ratios of the
      antidepressants. In conclusion, the presented results provide evidence that the
      observed in vitro distributive interactions between perazine and the
      antidepressants occur also in vivo, leading to a shift of the drugs from organs
      rich in lysosomes to those poor in these organella, in particular to the heart.
      Perazine and the antidepressants mutually increased the drug concentration ratios
      of heart/plasma and heart/lysosome-rich tissue, i.e. the heart/lung, heart/liver
      and heart/kidneys ratios. Similar results were obtained with lysosome-poor
      muscles in the case ofperazine. Moreover, the obtained results indicate that,
      apart from the lysosome density in the investigated tissues, the potential
      metabolic interactions in the liver and the order of drug circulation in a body
      have an important impact on the calculated drug concentration ratios.

PMID- 11334239
TI  - Anxiolytic-like effect of nafadotride and PNU 99194A, dopamine D3 receptor
      antagonists in animal models.
AB  - The obtained results indicate that dopamine D3 receptor antagonists, nafadotride
      and PNU 99194A, produced anxiolytic-like effect in animal models, which suggests
      a putative role of these drugs in the therapy of anxiety.

PMID- 11334240
TI  - Anxiolytic-like effects of group I metabotropic glutamate antagonist 2-methyl-6
      (phenylethynyl)-pyridine (MPEP) in rats.
AB  - We examined the anxiolytic-like activity of2-methyl-6-(phenylethynyl)-pyridine
      (MPEP) using the conflict drinking Vogel test in rats as a model. MPEP is a
      selective and brain-penetrable mGlu5 receptor antagonist, the most potent
      compound described so far. The results indicate that MPEP produced a dose
      dependent anticonflict effect in rats. These data suggest that selective mGlu5
      receptor antagonists may become a new class of anxiolytics.

PMID- 11334241
TI  - Effects of neuropeptides of the secretin/VIP/PACAP family on cyclic AMP formation
      in the chick hypothalamus and cerebral cortex.
AB  - Six neuropeptides: short and long form of the pituitary adenylate cyclase
      activating polypeptide (PACAP), i.e. PACAP27 and PACAP38, vasoactive intestinal
      peptide (VIP), peptide histidine-isoleucine (PHI), secretin and glucagon, members
      of the secretin/VIP/PACAP superfamily ofpolypeptides, were tested for their
      ability to stimulate cyclic AMP formation in [3H]adenine-prelabeled slices of the
      chick hypothalamus and cerebral cortex. Of the tested peptides, only PACAP evoked
      pronounced and significant responses in the two analyzed brain structures.
      Although magnitude of the responses varied in different experiments, the effects
      of both forms of PACAP were usually larger in the cerebral cortex than in the
      hypothalamus. Glucagon, PHI (both used at concentrations 0.01-1 microM) and VIP
      (0.1-3 microM) induced concentration-dependent yet comparatively small effects
      that did not reach statistical significance, while secretin (0.1-3 microM) had no
      effect.

PMID- 11334242
TI  - Influence of chronic imipramine administration on the CaM-KII activity in
      postsynaptic densities and synaptosomal plasma membrane fraction isolated from
      the rat frontal cortex and hippocampus.
AB  - CaM-KII exhibits broad distribution within neurons and discrete localization
      inside the cell, and it is highly abundant in the postsynaptic densities. The aim
      of the present study was to investigate the influence of chronic imipramine
      administration on the CaM-KII activity in postsynaptic densities and synaptosomal
      plasma membrane fraction isolated from the rat frontal cortex and hippocampus. In
      the present study, we showed that chronic imipramine administration did not
      affect the CaM-KII activity localized postsynaptically. Moreover, our results
      indicated that chronic imipramine treatment evoked a large (300%) increase in CaM
      KII activity in synaptosomal plasma membranes fraction isolated from frontal
      cortex.

PMID- 11334243
TI  - Kynurenic acid does not protect against nicotine-induced seizures in mice.
AB  - Kynurenic acid, an antagonist of glutamatergic ionotropic receptors and alpha7
      nicotinic cholinergic receptors failed to affect nicotine-induced convulsions in
      mice which may indicate that alpha7 nicotinic receptor-mediated events play no
      role in seizure activity produced by nicotine.

PMID- 11334244
TI  - Suppressive effect of TRH and imipramine on human interferon-gamma and
      interleukin-10 production in vitro.
AB  - It has been established that thyrotropin-releasing hormone (TRH) affects several
      aspects of immunoreactivity, e.g. production of pro-inflammatory cytokines, and
      enhances therapeutic efficiency of classic tricyclic antidepressants. On the
      other hand, it has been suggested that pro-inflammatory cytokines play a role in
      the etiology of depression, whereas the therapeutic efficacy of antidepressants
      is related to their negative immunoregulatory effect. In order to verify the
      hypothesis that the TRH-induced increase in the therapeutic efficiency of classic
      tricyclic antidepressants results from synergistic inhibitory effects of those
      two agents on the secretion of pro-inflammatory cytokines, we studied the effect
      of imipramine appliedjointly with TRH on the production of IFN-gamma and IL-10 by
      human whole blood cells stimulated in vitro by mitogens. A significant decrease
      in the production of IFN-gamma and IL-10 cytokines, by 36% and 34%, respectively,
      was observed in cells stimulated with mitogens and co-incubated with imipramine
      and TRH (either given at a dose of 10(-5) M). Under the same conditions, TRH
      alone did not change the production of those cytokines. Furthermore, imipramine
      alone decreased, not statistically significantly, though, the production of IFN
      gamma. Hence our data only partly support the above-mentioned hypothesis, since
      TRH and imipramine applied jointly suppress the production of both the pro
      inflammatory IFN-gamma and the anti-inflammatory IL-10 cytokines.

PMID- 11334245
TI  - Worrisome news from Mexico: drug resistance and DNA fingerprinting.

PMID- 11334246
TI  - They have given us the ammunition--we should use it.

PMID- 11334247
TI  - The responsibility of the tobacco industry for the tobacco pandemic.

PMID- 11334248
TI  - Socio-demographic determinants of smoking among low-income women in Aleppo,
      Syria.
AB  - OBJECTIVES: To determine the spread and sociodemographic correlates of smoking
      among low-income women in Aleppo, Syria. METHODS: A sample of 412 women was
      recruited from eight randomly selected primary care centres (total number 22) in
      Aleppo. The response rate was 97.2%, the mean age of participants was 28 (+/-
      8.4) years, and married women constituted 88.3% of those studied. A special
      questionnaire was prepared for study purposes, and interviews were conducted in
      an anonymous, one-to-one fashion. RESULTS: Current smoking and daily smoking were
      found among respectively 16.5% and 7.5% of those investigated. Smokers were
      older, economically better off and came from smaller households (P < 0.05 for
      all) than non-smokers. They also were more likely to be non-Arabs, Christians,
      and city residents than nonsmokers (P < 0.05 for all). Mental morbidity and
      physical abuse were both associated with smoking among those investigated (P < or
      = 0.05). Smokers among married women were more likely to marry later, to marry a
      nonrelative, to be older at the birth of their first child, and were less likely
      to live with members of their husband's family (P < 0.05 for all). Multivariate
      predictors of smoking status among married women were race, residence, household,
      consanguinity, working, mental morbidity and physical abuse. CONCLUSIONS: Our
      data show that the level of smoking among poor women in this society is still low
      compared to that of men, but it is higher than that of women in other social
      strata studied. Women's smoking is found to be associated with a less tradition
      oriented social profile.

PMID- 11334249
TI  - A clinic-based molecular epidemiologic study of tuberculosis in Monterrey,
      Mexico.
AB  - SETTING: A tuberculosis clinic associated with a university hospital in
      Monterrey, Mexico, an urban community with high tuberculosis incidence.
      OBJECTIVE: To determine the diversity of DNA fingerprint patterns and the extent
      of drug resistance of Mycobacterium tuberculosis isolates from patients who
      attended the clinic. DESIGN: Isolates of M. tuberculosis obtained from 186
      patients during the period from 31 January 1996 to 31 March 1998 were tested for
      susceptibility to isoniazid, rifampicin, ethambutol and streptomycin. Demographic
      data and the social history of each patient were obtained prospectively by
      interview. The IS6110 DNA fingerprints were obtained for 166 of the 186 isolates.
      Secondary typing was carried out on isolates with fewer than six copies of
      IS6110. RESULTS: Thirty-two per cent of the tested isolates (60/ 186) were drug
      resistant, and 18% (33/186) were multidrug-resistant. Approximately 55% of the
      resistant isolates (33/60) were attributed to acquired resistance. A total of 106
      different IS6110 fingerprint patterns were observed among the 166 fingerprinted
      isolates. Based on both IS6110 and pTBN12 fingerprinting, 65 (39%) of the 166
      isolates were part of 22 DNA fingerprint clusters. Various drug susceptibility
      patterns were seen in most clusters. CONCLUSION: Fingerprint clustering indicates
      extensive recent transmission of tuberculosis in patients attending the clinic.
      The prevalence of drug-resistant tuberculosis is high.

PMID- 11334250
TI  - Infection and disease among household contacts of patients with multidrug
      resistant tuberculosis.
AB  - SETTING: Urban public teaching and referral hospital in Espirito Santo, Brazil.
      OBJECTIVE: To assess whether rates of infection and progression to active
      tuberculosis (TB) differed between household contacts of patients with multidrug
      resistant (MDR) and drug susceptible (DS) pulmonary tuberculosis. DESIGN:
      Household contacts were assessed for evidence of TB infection and disease by
      purified protein derivative (PPD) skin testing, physical examination, chest X
      ray, and sputum smear and culture. RESULTS: Among 133 close contacts of patients
      with MDR-TB, 44% were PPD-positive (> or =10 mm) compared to 37% of 231 contacts
      of the DS-TB cases (P = 0.18, chi2 test, OR 1.2, 95%CI 0.8-2). In a multivariate
      logistic regression analysis, after allowance for between-household variation in
      PPD responses, PPD positivity among household contacts of patients with MDR-TB
      remained comparable to PPD positivity in contacts of patients with DS-TB (OR 2.1,
      95%CI 0.7-6.5). Respectively six (4%) and 11 (4%) contacts of the MDR- and DS-TB
      cases were found to have active TB at the time of initial evaluation or during
      follow-up (P = 0.78, chi2 test). Five of six contacts of MDR-TB cases and nine of
      nine contacts of DS-TB cases who developed TB, and for whom drug susceptibility
      test results were available, had the same bacterial susceptibility profiles as
      their index cases. DNA fingerprinting analysis of Mycobacterium tuberculosis
      isolates was identical between household contacts with active TB and the index
      MDR or DS-TB case for all 14 pairs compared. CONCLUSION: Our data suggest that
      the prevalence of tuberculous infection and progression to active TB among
      household contacts exposed to DS and MDR-TB cases is comparable, despite a longer
      duration of exposure of contacts to the index case in patients with MDR-TB.

PMID- 11334251
TI  - Evaluation of tuberculosis control by periodic or routine susceptibility testing
      in previously treated cases.
AB  - SETTING: A national tuberculosis control programme (NTP) disposing of baseline
      drug resistance rates and using 2EHRZ/6TH in the treatment of new cases.
      OBJECTIVE: To estimate the extent of drug resistance created by the NTP. DESIGN:
      Resistance rates in 2EHRZ/6TH failure and relapse cases were compared to
      baseline, and resistance profiles of repeat isolates were checked. Numbers of
      observed resistant failures were compared to numbers expected due to pre-existing
      resistance. Trends of resistance in combined new and previously treated cases
      were extrapolated. RESULTS: High drug resistance rates were observed. Changes in
      resistance to streptomycin, the virtual absence of documented acquired resistance
      and a close match of observed with expected resistant failures all indicated
      accumulation of primary drug resistance as the main mechanism. Resistance in
      relapse/failure cases showed a significantly declining trend, and estimated
      combined drug resistance decreased rapidly. CONCLUSIONS: Drug resistance in
      previously treated cases seems to consist of passed-on primary rather than true
      acquired resistance. A one-time survey is thus confusing, but continuous routine
      testing may constitute the best drug resistance monitoring method. Cases
      previously treated with short-course chemotherapy may show drug resistance much
      more frequently than generally assumed, and all should receive a re-treatment
      regimen. The 2EHRZ/6TH regimen proved very safe under field conditions, causing
      no 'amplification' towards multidrug resistance and almost no acquired isoniazid
      resistance. Implementation of this regimen, together with a standardised re
      treatment regimen, seemed to rapidly reduce isoniazid as well as multidrug
      resistance levels, despite the fact that directly observed treatment was not
      strictly applied.

PMID- 11334252
TI  - Heteroresistance in Mycobacterium tuberculosis.
AB  - SETTING: Drug resistance in Mycobacterium tuberculosis is often linked to
      specific mutations in a limited number of resistance genes. Detection of these
      mutations in a cultured isolate can predict the resistant phenotype. Genotypic
      analysis of the mycobacteria directly in a clinical specimen would result in
      considerable time saving for resistance prediction. OBJECTIVE: To find out
      whether resistance-predicting genotypes of mycobacteria found after cultivation
      always give a good reflection of those in the original clinical sample. DESIGN:
      Restriction fragment length polymorphisms of repetitive polymerase chain reaction
      (PCR) amplification and cloning of PCR products were used as nonintegrative
      methods to describe the composition of katG, rpsL and embB genotypes involved in
      resistance to isoniazid, streptomycin and ethambutol, respectively, in the
      original sample. This result was then compared to the phenotypic resistance
      profile after cultivation. RESULTS: Using both methods, mixed, heteroresistant
      populations could be detected in almost every fifth analyzed sample (katG: 5 of
      16; rpsL: 3 of 17; embB: 1 of 21). Direct sequencing, a widely used integrative
      method, repeatedly failed to detect heteroresistance. CONCLUSION:
      Heteroresistance is a valid phenomenon in clinical tuberculosis. It is not rare
      and not restricted to a particular resistance gene, and is obscured by
      cultivation as well as by some, not all, culture-independent resistance
      prediction tests.

PMID- 11334253
TI  - Incidence of pulmonary tuberculosis in Korean civil servants: second study, 1992
      1994.
AB  - SETTING: A survey based on biennial medical examinations for civil servants,
      including school teachers. OBJECTIVE: To estimate the incidence of pulmonary
      tuberculosis (PTB) for the general population from a sample survey, and to
      compare it with the previous results from 1988-1990. DESIGN: A retrospective
      follow-up study which started in April 1996 and ended in December 1997.
      Development of PTB among all South Korean civil servants who were tuberculosis
      free in the 1992 biennial medical examination was followed up to the 1994 medical
      examination. The survey was based on newly-developed cases by 1) the findings of
      the biennial medical examination, 2) scrutiny of the medical records of all those
      claiming health insurance for tuberculosis, and 3) checking of the TB registers
      in all health centres during the period. Civil servants constituted 2.6% of the
      Korean population aged 20 to 64. RESULTS: Of 958137 subjects who were found to be
      TB-free in the 1992 medical examination, 957216 were eligible for the study.
      Radiologically active PTB was found in 4146 cases over the 2-year period of the
      study. Bacteriological examinations were performed in 3306 patients: there were
      1551 bacteriologically proven cases (46.9%), including 1049 smear-positives
      (31.7%) and 502 smear-negative culture-positives (15.2%). The age-sex adjusted
      incidence rate for the general population was 202/100000 in radiologically active
      PTB, 81/100000 in bacteriologically proven PTB, and 54/100000 in smear-positive
      PTB. Overall PTB incidence rates were higher in males (240/100000) than in
      females (163/100000), and in the age group 20-24 years (280/ 100 000) than in the
      other age groups. CONCLUSION: Comparing the 1992-1994 PTB incidence with that
      observed in the 1988-1990 survey, the highest incidence was observed among young
      adults in both surveys, and it had not changed over time.

PMID- 11334254
TI  - Public-private partnership in tuberculosis control: experience in Hyderabad,
      India.
AB  - SETTING: Hyderabad, India. OBJECTIVE: To determine whether private practitioners
      and the government can collaborate with a nongovernmental intermediary to
      implement DOTS effectively. DESIGN: A non-profit hospital provided DOTS services
      to a population of 100000 for 3 years, then expanded coverage to 500000 in
      October 1998. A hospital physician visited all private practitioners, encouraged
      them to refer patients, and gave feedback on each patient referred. After
      diagnosis, patients received directly observed treatment free of charge at the
      trust hospital or at 30 conveniently located small hospitals operated by local
      private practitioners. No financial incentives were used to encourage physicians
      to refer patients or to provide treatment observation. Diagnosis, treatment, and
      case and outcome definitions were performed as per DOTS policies; medicines and
      laboratory reagents were provided by the government. RESULTS: All 244 allopathic
      and 114 non-allopathic physicians practising in the area agreed to participate;
      59% referred at least one patient. Of 2244 persons referred, 969 (43%) had
      tuberculosis. Physicians had obtained chest radiographs on 80% of patients before
      referral for sputum microscopy. The detection rate increased from 50 to
      200/100000 over the first 2-3 years of the project, and has increased gradually
      since expansion; 90% of new smear-positive patients and 77% of re-treatment
      patients were successfully treated. Compared with those treated at a neighbouring
      government DOTS centre, patients in this project paid less for diagnosis ($5 vs.
      $20) and treatment ($1 vs. $11), largely due to lower transport costs.
      CONCLUSIONS: Collaborative efforts between private practitioners and the
      government can achieve moderate-high rates of case detection and high rates of
      treatment success. Public-private services appeared to be more convenient to
      patients, who paid less for care and were less likely to miss work in order to
      participate in DOTS. Clearly defined roles and expectations and frequent
      communication are essential to success. An institution such as a non-profit
      hospital can serve as an effective intermediary between the government DOTS
      programme and private practitioners.

PMID- 11334255
TI  - Under-diagnosis of smear-positive pulmonary tuberculosis in Nairobi, Kenya.
AB  - SETTING: Nairobi City Council Chest Clinic, Nairobi, Kenya. OBJECTIVE: To
      determine if under-reading of sputum smears is a contributing factor in the
      disproportionate increase in smear-negative tuberculosis in Nairobi, Kenya.
      METHODOLOGY: Between October 1997 and November 1998, patients fulfilling the
      local programme definition of smear-negative presumed pulmonary tuberculosis were
      enrolled in the study. Two further sputum specimens were collected for
      examination in a research laboratory by fluorescence microscopy. RESULTS: Of 163
      adult subjects enrolled, 55% were seropositive for the human immunodeficiency
      virus type 1 (HIV-1). One hundred subjects had had two pre-study sputum smears
      assessed before recruitment and produced two further sputum specimens for re
      examination in the research laboratory; of these 19 (19%) were sputum smear
      positive on re-examination and a further seven (7%) became smear-positive on
      second re-examination. CONCLUSIONS: Of those patients with smear-negative
      presumed pulmonary tuberculosis by the local programme definition, 26% were smear
      positive when reexamined carefully with two repeat sputum smears. This suggests
      that the high rates of smear-negative tuberculosis being seen may in part be due
      to under-reading. This is probably as a result of the overwhelming burden of
      tuberculosis leading to over rapid and inaccurate sputum examination. Retraining
      of existing technicians and training of more technicians is likely to reduce
      underreading and increase the yield of smear-positive tuberculosis. This finding
      also stresses the need for regular quality assurance.

PMID- 11334256
TI  - Utility of nucleic acid amplification techniques for the diagnosis of pulmonary
      tuberculosis in sub-Saharan Africa.
AB  - SETTING: Lusaka, Zambia. OBJECTIVES: To investigate the utility of nucleic
      amplification tests for the diagnosis of pulmonary tuberculosis in a resource
      poor setting with a high incidence of human immunodeficiency virus (HIV). DESIGN:
      Sputum specimens from suspects attending a referral chest clinic were examined by
      low-cost 'in-house' one-tube nested polymerase chain reaction (PCR), the enhanced
      Gen-Probe Amplified Mycobacterium Direct Test (AMTD), auramine smear and
      Lowenstein-Jensen culture. RESULTS: PCR and AMTD detected respectively 80% and
      92% of smear-positive specimens and 40% and 60% of smear-negative, culture
      positive specimens. AMTD was positive for 18 culture-negative suspects;
      subsequent investigation indicated these to be six confirmed tuberculosis
      patients, nine judged from radiological data and clinical follow-up studies to
      have pulmonary tuberculosis, and three non-tuberculosis patients. Sensitivity for
      smear, culture, PCR and AMTD, when compared to a gold standard incorporating both
      microbiological and clinical data, was respectively 29%, 69%, 55% and 81%.
      CONCLUSION: In this setting, the sensitivity of the low-cost PCR proved
      insufficient for its effective use as a tool for diagnosing pulmonary
      tuberculosis, while AMTD performed considerably better than the current
      laboratory methods for diagnosis of pulmonary tuberculosis. However, the high
      cost of this technology may limit its application in the public sector of low
      income countries.

PMID- 11334257
TI  - Paradoxical tuberculous reactions in HIV-infected patients.
AB  - OBJECTIVE: To report the occurrence of paradoxical tuberculous reactions in two
      patients co-infected with HIV/AIDS, and to review the literature on this subject.
      PATIENTS: Two HIV-infected patients with miliary tuberculosis who developed
      expansion of tuberculous disease at a new site following initiation of anti
      tuberculosis treatment, with or without antiretroviral treatment, and an
      additional 29 literature cases of HIV infection with paradoxical tuberculous
      reaction. RESULTS: Index episodes of tuberculosis included pulmonary, nodal,
      cutaneous and miliary forms. Types of paradoxical reactions included enlargement
      of lymph nodes or appearance of new lymphadenopathy, radiographic worsening of
      pulmonary infiltrates or appearance of miliary infiltrates or pleural effusions,
      peritonitis, tenosynovitis, worsening or development of new soft tissue lesions,
      and appearance of new contrast-enhancing intracranial tuberculomas. The
      occurrence of paradoxical reactions appears more temporally related to
      antiretroviral than to anti-tuberculosis therapy. CONCLUSIONS: It is important
      for clinicians to recognise paradoxical tuberculous reactions as inflammatory
      responses to treatment, and to understand that they do not necessarily indicate
      drug resistance or an inadequate response to therapy. Anti-tuberculosis and
      antiretroviral drug regimens need not be altered or discontinued, although a
      short course of corticosteroids may be useful in reducing inflammation.

PMID- 11334258
TI  - A unified treatment regimen for new cases of tuberculosis in resource-poor
      countries: a study in a rural district in Malawi.
AB  - An oral ambulatory unified treatment regimen was introduced in Ntcheu District,
      Malawi, between April 1996 and June 1997 for all new patients (600) with
      tuberculosis (TB). There was no change in the case finding pattern compared with
      the previous 5 years; 65% of new smear-positive pulmonary tuberculosis (PTB)
      patients completed treatment, not significantly different compared with the
      previous 3 years. Treatment completion was significantly lower in patients with
      smear-negative PTB and extra-pulmonary tuberculosis, due mainly to high mortality
      rates (40% and 41% respectively). In a rural district with high human
      immunodeficiency virus sero-prevalence rates in TB patients, case finding and end
      of treatment outcome of the oral unified regimen were comparable to those of
      previous regimens.

PMID- 11334259
TI  - Utility of PCR assays for rapid diagnosis of BCG infection in children.
AB  - We report Mycobacterium bovis BCG infection in two children vaccinated with BCG
      (Tokyo strain) on the first day of life. Their diagnoses were made by biopsy of
      skin lesions and pus from an anterior chest wall abscess, respectively, yielding
      a positive culture of mycobacteria fully susceptible to rifampicin, isoniazid and
      ethambutol, but resistant to pyrazinamide. M. bovis BCG was identified by a
      negative niacin test, absence of nitrate reductase and resistance to pyrazinamide
      and cycloserine. The diagnoses were further confirmed by a combination of an
      allele-specific polymerase chain reaction ated strain of Mycobacterium bovis, is
      the only available vaccine for the prevention of tuberculosis. Although
      complications are rare after BCG vaccination and the outcome is usually
      favourable, serious BCG infections can occur. We report two cases of M. bovis BCG
      infection in children, a 4-year-old immunocompetent girl and an 8-month-old
      immunodeficient boy. To our knowledge, this is the first report of BCG
      complications in children in which two recently developed polymerase chain
      reaction (PCR) based methods were used for rapid identification of M. bovis BCG
      infection. (PCR) and a multiplex PCR method. Based on the drug susceptibility
      results, treatment with rifampicin, isoniazid and ethambutol was instituted. One
      patient (Case 1) improved clinically and is well after treatment. However, the
      other patient with severe combined immunodeficiency died of disseminated BCG
      infection in spite of intensive anti-tuberculosis therapy. Although BCG is
      considered to be a safe vaccine, it should be kept in mind that complications
      related to BCG do occur.

PMID- 11334260
TI  - Higher activity of morphazinamide over pyrazinamide against intracellular.

PMID- 11334261
TI  - More on periphery to centre quality control of sputum smear microscopy and 'rapid
      fading' of Ziehi-Neelsen staining.

PMID- 11334262
TI  - Inhibition of drug metabolism in human liver microsomes by nizatidine, cimetidine
      and omeprazole.
AB  - 1. The inhibitory effects of cimetidine, nizatidine and omeprazole on the
      metabolic activity of CYP2C9, 2C19, 2D6 and 3A were investigated in human liver
      microsomes. Both cimetidine and omeprazole inhibited each of the CYP subfamily
      enzymes; in particular, omeprazole extensively inhibited the hydroxylation of S
      mephenytoin (CYP2C19, Ki = 7.1 microM). Nizatidine exhibited no inhibition of any
      of the CYP isoforms examined. 2. Cimetidine inhibited the hydroxylation of
      tolbutamide but not of diclofenac, whereas omeprazole inhibited the hydroxylation
      of diclofenac but not that of tolbutamide. The ability to inhibit CYP2C9 varied
      with incubation time, as measured by the metabolic rate constant for the
      substrates. Therefore, suitable substrates and incubation times must be selected
      in inhibition studies examining metabolic clearance and the mechanism of
      inhibition of these drugs. 3. Nizatidine did not inhibit the metabolism of
      cisapride, glibenclamide, benidipine and simvastatin. Omeprazole inhibited the
      metabolism of cisapride (Ki = 0.4 microM), glibenclamide (11.7 microM) and
      benidipine (6.5 microM), whereas cimetidine inhibited the metabolism of
      glibenclamide (11.6 microM). To avoid drug-drug interactions, care needs to be
      taken to select suitable medicines for co-administration with anti-ulcer drugs.

PMID- 11334263
TI  - Non-enzymatic reduction of aliphatic tertiary amine N-oxides mediated by the haem
      moiety of cytochrome P450.
AB  - 1. The mechanism of reduction of aliphatic tertiary amine N-oxides to tertiary
      amines in liver microsomes was examined and a novel type of reduction by
      cytochrome P450 was found. 2. Rat liver microsomes exhibited a significant N
      oxide reductase activity toward brucine N-oxide and imipramine N-oxide in the
      presence of both NAD(P)H and FAD under anaerobic conditions. These N-oxide
      reductase activities were inhibited by carbon monoxide or air. However, the
      activities were not abolished by boiling the microsomes; indeed, in the case of
      brucine N-oxide, the activity was enhanced. 3. The activity toward brucine N
      oxide was also observed after the conversion of cytochrome P450 to cytochrome
      P420. Cytochrome P4502B1 alone exhibited the reductase activity in the presence
      of both NAD(P)H and FAD. After the removal of haem from cytochrome P4502B1, the
      activity was observed in the haem moiety, but not in the cytochrome P450
      apoprotein. 4. Photochemically reduced FAD was effective in the reduction in
      place of NAD(P)H and FAD. 5. The N-oxide reduction appears to proceed non
      enzymatically, catalysed by the haem group of cytochrome P450 in the presence of
      a reduced flavin.

PMID- 11334264
TI  - Lack of interaction between bropirimine and 5-fluorouracil on human
      dihydropyrimidine dehydrogenase.
AB  - 1. Bropirimine (2-amino-5-bromo-6-phenyl-4-pyrimidinone) is a member of a class
      of antineoplastic agents that are administered concomitantly or sequentially with
      anticancer 5-fluorouracil (5-FU) prodrugs in clinical patients. Interactions
      between bropirimine and 5-fluorouracil (5-FU) were investigated on
      dihydropyrimidine dehydrogenase (DPD) activity, the rate-limiting enzyme of 5-FU
      metabolism, in human liver cytosol. Apparent DPD activity was determined by
      measuring the recovery of [14C]5-FU by HPLC. 2. The apparent activity of 5-FU
      metabolism (2.1-100 microM) showed a linear relationship in the Eadie-Hofstee
      plot in the pooled cytosol, suggesting that a single enzyme is responsible for
      apparent 5-FU metabolism. Km and Vmax were estimated to be 23 microM and 0.32
      nmol min(-1) mg(-1) protein, respectively. Apparent DPD activity for 5-FU (25
      microM) in the cytosol from 12 individual donors ranged from 0.017 to 0.39 (0.16
      +/- 0.12) nmol min(-1) mg(-1) protein, indicating a large intersubject variance.
      3. The suicidal inactivators of the DPD enzyme, (E)-5-(2-bromovinyl)uracil and 5
      bromouracil (6.3-50 microM), illustrated concentration-dependent inhibition on
      DPD activity. Isocytosine (6.3-100 microM), used as a negative control, did not
      affect DPD activity. Bropirimine (6.3-100 microM) also did not show any
      inhibition of DPD activity. Therefore, bropirimine is unlikely to cause increases
      in 5-FU levels in clinical patients after co-administration of bropirimine with 5
      FU prodrugs.

PMID- 11334265
TI  - Pharmacokinetics and system linearity of tea catechins in rat.
AB  - 1. The pharmacokinetics and dose proportionality of three tea catechins were
      assessed. 2. Male Sprague-Dawley rats (210-230 g) received intravenous (i.v.)
      doses (50, 100, 200 and 300 mg kg(-1)) of a decaffeinated tea fraction containing
      (-)-epicatechin (EC: 5%), (-)-epigallocatechin gallate (EGCG: 50%) and (-)
      epicatechin gallate (ECG: 13%). 3. Catechins in plasma, urine and faeces were
      quantitated by HPLC. 4. A two-compartment model was utilized to describe the bi
      exponential disposition exhibited by the three catechins. 5. Over this dose
      range, the central distribution volume (Vc) for these catechins increased
      significantly (p < 0.05) from 0.17-0.34 to 0.42-0.66 l kg(-1). 6. A concentration
      dependent increase in the plasma free fraction of catechins that mirrored the
      increases in Vc was observed. 7. The estimates of steady-state volume of
      distribution (Vss) were between 0.68 and 2.08 l kg(-1) at the lowest dose, and
      tended to increase with dose. 8. Appreciable amount of catechins partitioned into
      red blood cells (range 9-43%) and was apparently independent of concentration. 9.
      The mean elimination half-life (t(1/2,beta)) for EC, EGCG and ECG across doses
      were 43, 124, and 222 min respectively, and were invariant with dose. 10.
      Parallel to Vc, a 2-3-fold dose-dependent increase (p < 0.05) in systemic
      clearance (CL) was observed for the three catechins. 11. Urinary recovery was
      highest (21-31%) for EC, while those for EGCG and ECG was only approximately 3
      5%. 12. Faecal recoveries of the catechins were between 0.5 and 5%. 13. In
      conclusion, the pharmacokinetics of the catechins appeared to be non-linear; dose
      dependent changes in xenobiotic distribution might contribute to this
      observation.

PMID- 11334266
TI  - The influence of apolipoprotein E genotype on outcome after spontaneous
      subarachnoid hemorrhage: a preliminary study.
AB  - OBJECTIVE: Possession of an apolipoprotein E (APOE)epsilon4 allele has been shown
      to be associated with a poor outcome after closed head injury and spontaneous
      intracerebral hemorrhage but not after ischemic stroke. This study assessed the
      influence of the APOE genotype on outcome in patients admitted to a neurosurgical
      unit with spontaneous subarachnoid hemorrhage. METHODS: A total of 100 patients
      with spontaneous subarachnoid hemorrhage were studied. Four patients were
      excluded because the diagnosis of subarachnoid hemorrhage was not confirmed. The
      incidence of rehemorrhage and delayed ischemia and the outcome at 6 months were
      determined using the Glasgow Outcome Scale. APOE genotypes were determined by
      polymerase chain reaction and restriction enzyme digestion. RESULTS: Allele
      frequencies in this patient group were 0.04 for epsilon2, 0.86 for epsilon3, and
      0.1 for epsilon4. Of 96 patients, 72 had an aneurysmal hemorrhage and 1 had a
      hemorrhage from an arteriovenous malformation. In 14 patients, the results of
      angiography were negative, and in 9, no angiogram was performed. Of the 96
      patients, 20 had one or more epsilon4 allele. Outcome at 6 months was no worse in
      patients with one or more epsilon4 allele than in those with no epsilon4 allele
      (odds ratio, 0.98; 95% confidence interval, 0.35-2.74). None of the 12 patients
      who experienced delayed ischemic deterioration had an epsilon4 allele. Of the 20
      patients with an epsilon4 allele, 3 had a rehemorrhage, as compared with 6 of 76
      patients without an epsilon4 allele. CONCLUSION: There was underrepresentation of
      the epsilon4 allele in this group when compared with previously studied cases of
      subarachnoid hemorrhage with a fatal outcome and with the general population.
      This suggests that patients with the epsilon4 allele who have a subarachnoid
      hemorrhage are less likely to be admitted to a neurosurgical unit. This study
      does not support an association between possession of an epsilon4 allele and poor
      outcome in patients admitted to a neurosurgical unit with spontaneous
      subarachnoid hemorrhage, although the wide confidence interval does not preclude
      a clinically relevant association between APOE genotype and outcome. The findings
      indicate that an association between genotype and the development of delayed
      ischemic complications after subarachnoid hemorrhage may be possible.

PMID- 11334267
TI  - Surgical management of clinoidal meningiomas.
AB  - OBJECTIVE: Surgical outcome has been less than desirable in the management of
      patients with clinoidal meningiomas in the past, and little attention has been
      directed at improving their visual function. The purpose of this article is to
      advocate an available cranial base technique for removing these difficult tumors
      and to delineate the technique's advantages that aid in achieving an improved
      extent of tumor resection and enhancing the patients' overall outcome,
      particularly their visual outcome. METHODS: A retrospective analysis was
      performed on 15 consecutive patients with clinoidal meningiomas (including a
      patient with hemangiopericytoma) who underwent surgical resection at the
      Cleveland Clinic Foundation between June 1995 and January 2000. A cranial base
      technique consisting of extradural anterior clinoidectomy, coupled with optic
      canal unroofing and optic sheath opening, was used in 13 patients, and standard
      pterional craniotomy was used in 2. Eight of 15 patients had significant visual
      deficits preoperatively. All patients had thorough preoperative and postoperative
      ophthalmological evaluations. The follow-up period ranged from 6 to 60 months
      (mean, 37.2 mo). RESULTS: Total resection was achieved in 13 (86.7%) of the 15
      patients in this series, and the majority of the patients with preoperative
      visual impairment experienced significant improvement (6 of 8 patients; 75%).
      CONCLUSION: In the majority of patients with clinoidal meningiomas, total
      resection may be achieved with minimal complications. For large tumors encasing
      the optic nerve and internal carotid artery, or for those tumors causing
      preoperative visual impairment, use of the cranial base technique delineated in
      this study may lead to significant improvement in the patients' visual and
      overall outcomes.

PMID- 11334268
TI  - Radiosurgical management of benign cavernous sinus tumors: dose profiles and
      acute complications.
AB  - OBJECTIVE: Radiosurgery has emerged as an alternative treatment modality for
      cranial base tumors in patients deemed not suited for primary surgical
      extirpation, patients with recurrent or residual tumor after open surgery, or
      patients who refuse surgical treatment. We review our short-term experience with
      radiosurgical management of cavernous sinus region tumors with the Leksell gamma
      knife. METHODS: From August 1994 to February 1999, 69 patients with cavernous
      sinus lesions were treated in 72 separate treatment sessions. The tumor type
      distribution was 29 pituitary adenomas, 35 meningiomas, 4 schwannomas, and 1
      paraganglioma. The median follow-up was 122 weeks. Lesions were stratified
      according to a five-level surgical grade. The grade distribution of the tumors
      was as follows: Grade I, 13; Grade II, 21; Grade III, 19; Grade IV, 12; Grade V,
      4. Median tumor volume was 4.7 cm3. The median radiation dose was 15 Gy to the
      50% isodose line. Median maximal radiation dose was 30 Gy. RESULTS: Analysis of
      tumor characteristics and radiation dose to optic nerve and pontine structures
      revealed a significant correlation between distance and dose. Much lower
      correlation coefficients were found between tumor volume and dose. One lesion in
      this series had evidence of transient progression and later regression on follow
      up radiographic studies. No other lesions in this series were demonstrated to
      have exhibited progression. Complications after radiosurgical treatment were
      uncommon. Two patients had cranial nerve deficits after treatment. One patient
      with a surgical Grade III pituitary adenoma had VIth cranial nerve palsy 25
      months after radiosurgical treatment that spontaneously resolved 10 months later.
      A patient with a bilateral pituitary adenoma experienced bilateral VIth cranial
      nerve palsy 3 months after treatment that had not resolved at 35 months after
      treatment. Six patients with preoperative cranial nerve deficits experienced
      resolution or improvement of their deficits after treatment. One patient with a
      prolactin-secreting adenoma experienced normalization of endocrine function with
      return of menses. CONCLUSION: Radiosurgical treatment represents an important
      advance in the management of cavernous sinus tumors, with low risk of
      neurological deficit in comparison with open surgical treatment, even in patients
      with high surgical grades.

PMID- 11334269
TI  - Association of total dose intensity of chemotherapy in primary central nervous
      system lymphoma (human non-acquired immunodeficiency syndrome) and survival.
AB  - OBJECTIVE: The importance of enhanced drug delivery in patients with central
      nervous system (CNS) malignancies has not yet been demonstrated conclusively.
      Intra-arterial chemotherapy in combination with osmotic bloodbrain barrier
      disruption (BBBD) increases drug delivery to tumor by 2- to 5-fold and to
      surrounding brain tissue by 10- to 100-fold as compared with intravenous
      administration of chemotherapy. Primary CNS lymphoma (PCNSL) is an excellent
      model for studying dose intensity because PCNSL is a highly infiltrative,
      chemosensitive, primary CNS malignancy in which the integrity of the blood-brain
      barrier is highly variable. METHODS: Survival time was assessed in 74 non
      acquired immunodeficiency syndrome patients with PCNSL who underwent a total of
      1047 BBBD procedures. Total dose intensity is estimated by using the number of
      intraarterial infusions or a cumulative degree of BBBD score. RESULTS: Using
      proportional hazards multivariable analyses to adjust for baseline
      characteristics, survival was significantly associated with the total intensity
      of BBBD (P < 0.05). Additional statistical analyses demonstrate that survival
      bias does not fully explain these associations. Even when only patients who
      attained a complete response are considered, increased dose intensity resulted in
      increased survival. CONCLUSION: In patients with PCNSL, a chemotherapy-responsive
      tumor type, survival time is highly associated with total drug dose delivered,
      even in analyses designed to control for potential survival biases. These results
      probably constitute the strongest evidence to date of the importance of total
      dose intensity in treating CNS malignancies.

PMID- 11334270
TI  - Spontaneous intraparenchymal hemorrhage in full-term neonates.
AB  - OBJECTIVE: Spontaneous intraparenchymal hemorrhage is extremely rare in full-term
      newborns. Reports to date have been limited to descriptions of individual cases,
      small groups within larger studies of intracranial hemorrhage, and one series of
      four patients. Structural lesions are rarely identified, and the majority of
      patients described have been managed without surgical intervention. METHODS:
      Analysis of a computerized database of pediatric neurosurgical patients from
      January 1960 to February 2000 identified full-term newborns younger than 3 months
      of age with nontraumatic intraparenchymal hemorrhages. Prenatal histories, labor
      and delivery histories, clinical presentations, imaging studies, management, and
      outcomes were reviewed. RESULTS: Eleven full-term newborns with spontaneous
      intraparenchymal hemorrhages were identified. The majority had normal prenatal
      courses. Most presented within the first 2 days of life (6 of 11 patients), and
      the most common presenting sign was seizure (7 of 11 patients). No cause was
      identified in 6 of 11 patients; the remainder were attributed to coagulopathy (n
      = 3), ruptured intracranial aneurysm (n = 1), or hemorrhagic infarction (n = 1).
      Eight patients underwent surgical hematoma evacuation on the basis of
      radiographic evidence of significant mass effect, evidence of signs of elevated
      intracranial pressure, or both. Three patients did not receive surgical
      intervention. There were no subsequent hemorrhages or deaths during a mean follow
      up period of 4.5 years (range, 1-16 yr). Four patients had normal neurological
      outcomes, four had motor deficits (one of whom additionally demonstrated
      cognitive delay), and three had delayed speech. CONCLUSION: No cause is
      identified in most newborns with spontaneous intraparenchymal hemorrhage.
      Radiographic evidence of mass effect or signs of elevated intracranial pressure
      may necessitate surgical hematoma evacuation. Outcome varies widely and may be
      normal, even in patients with sizeable intraparenchymal hemorrhages.

PMID- 11334271
TI  - Analysis of the posterior fossa in children with the Chiari 0 malformation.
AB  - OBJECTIVE: We previously reported the resolution of syringohydromyelia without
      cerebellar tonsillar ectopia in five patients after posterior fossa decompression
      of the so-called Chiari 0 malformation. A sixth patient is described. In this
      study, the anatomy of the posterior fossa is analyzed using radiological imaging,
      enabling features of the posterior fossa in this uncommon subgroup of children to
      be characterized. METHODS: Multiple measurements were made on magnetic resonance
      imaging studies in six children with Chiari 0 malformation to determine the
      position of the brainstem relative to the foramen magnum. Fifty children with
      normal magnetic resonance imaging studies of the brain were used as controls.
      RESULTS: All children with a Chiari 0 malformation were found to have the
      following positive results: obices that were located more than 2 standard
      deviations below normal, an increase in the anteroposterior midsagittal distance
      of the spinomedullary junction at the level of the foramen magnum, an increase in
      the angle between the floor of the fourth ventricle and clivus, and an increase
      in the anteroposterior midsagittal distance of the foramen magnum. CONCLUSION:
      The findings of this study suggest that the contents of the posterior fossa are
      indeed compromised and/or distorted in patients with syringohydromyelia but no
      tonsillar ectopia. In this group, the brainstem was caudally displaced more than
      3 standard deviations below normal.

PMID- 11334272
TI  - Spinal cord stimulation for nonspecific limb pain versus neuropathic pain and
      spontaneous versus evoked pain.
AB  - OBJECTIVE: To compare the outcome of spinal cord stimulation (SCS) in patients
      with nonspecific limb pain versus patients with neuropathic pain syndromes and in
      patients with spontaneous versus evoked pain. METHODS: A retrospective review of
      122 patients accepted for treatment with SCS between January 1990 and December
      1998 was conducted. All patients first underwent a trial of SCS with a monopolar
      epidural electrode. Seventy-four patients had a successful trial and underwent
      permanent implantation of the monopolar electrode used for the trial (19
      patients), or a quadripolar electrode (53 patients), or a Resume quadripolar
      electrode via laminotomy (2 patients). RESULTS: Of the 74 patients, 60.7%
      underwent implantation of a permanent device and were followed for an average of
      3.9 years (range, 0.3-9 yr). Early failure (within 1 yr) occurred in 20.3% of
      patients, and late failure (after 1 yr) occurred in 33.8% of patients. Overall,
      45.9% of patients were still receiving SCS at latest follow-up. Successful SCS
      (>50% reduction in pain for 1 yr) occurred in 83.3% of patients with nonspecific
      leg pain, 89.5% of patients with limb pain associated with root injury, and 73.9%
      of patients with nerve neuropathic pain. SCS was less effective for the control
      of allodynia or hyperpathia than for spontaneous pain associated with neuropathic
      pain syndromes. Third-party involvement did not influence outcome. There was a
      lesser incidence of surgical revisions when quadripolar leads were used than with
      monopolar electrodes. CONCLUSION: SCS is as effective for treating nonspecific
      limb pain as it is for treating neuropathic pain, including limb pain associated
      with root damage.

PMID- 11334273
TI  - Assessment of acutely unsuccessful attempts at detachable coiling in intracranial
      aneurysms.
AB  - OBJECTIVE: Guglielmi detachable coiling (GDC) has quickly become the most common
      endovascular method for the treatment of intracranial aneurysms. Although several
      published case series describe various authors' successful experiences or
      complications, few have elaborated on failed attempts. We examined our experience
      with GDC, and we analyzed all failed attempts at coiling. METHODS: Patients who
      underwent endovascular procedures from September 1995 through July 1999 were
      identified using endovascular case logs and billing records. Patient charts were
      then reviewed retrospectively for failed attempts at GDC. A treatment failure was
      defined as an inability to place coils into an aneurysm, a GDC procedure-related
      complication resulting in death, or an acute rehemorrhage from a coiled aneurysm
      that indicated a failure of coils to prevent rerupture. Thromboembolic events and
      other nonfatal sources of morbidity that did not preclude coiling of the aneurysm
      were analyzed only to the extent that they prevented successful coiling of the
      aneurysm. RESULTS: From September 1995 to June 1999, 241 patients underwent GDC
      embolizations or attempts. In these patients, 35 procedures were unsuccessful,
      including 7 deaths from intraoperative or postoperative aneurysmal rerupture.
      Sixteen aneurysms could not be microcatheterized, nine of which were anterior
      communicating artery aneurysms. Coils from 13 wide-necked aneurysms (average
      fundus-to-neck ratio, <2) prolapsed into the parent vessel. Three procedures were
      abandoned when the aneurysms were found to have normal branches filling from the
      dome, and three additional procedures were abandoned for technical reasons. Five
      deaths resulted from intraoperative aneurysm rupture, and two patients died
      postoperatively from rerupture. CONCLUSION: The number of successful coiling
      procedures has increased with experience and improved technology. The procedure
      still involves risks, however, primarily for patients with subarachnoid
      hemorrhage.

PMID- 11334274
TI  - Transcranial electrical motor evoked potential monitoring for brain tumor
      resection.
AB  - OBJECTIVE: This study was designed to examine whether transcranial electrical
      motor evoked potential (MEP) monitoring is safe, feasible, and valuable for brain
      tumor surgery. METHODS: Fifty consecutive patients undergoing brain tumor
      resection were studied, using nitrous oxide/propofol anesthesia. MEPs were
      continuously recorded throughout surgery, using a Sentinel 4 evoked potential
      system (Axon Systems, Inc., Hauppauge, NY). The MEPs were elicited by
      transcranial electrical stimulation (train of 5; stimulation rate, 0.5-2 Hz;
      square wave pulse with a time constant of 0.5 ms; stimulation intensity, 40-160
      mA) through spiral electrodes placed over the primary motor cortex and were
      recorded by needle electrodes inserted into the contralateral orbicularis oris,
      biceps, abductor pollicis brevis, and anterior tibialis muscles. When MEP
      amplitudes decreased by more than 50%, MEP stimulation was repeated, with
      increased stimulation intensity, and MEP changes were reported to the surgeon.
      The motor function of each patient was examined before and after surgery, using a
      reproducible scale. The relationship between MEP amplitude decreases and
      worsening motor status was analyzed using linear regression. RESULTS:
      Preoperative neurological examinations revealed mild to moderate motor deficits
      (2/5 to 4/5) for 38% of patients (19 of 50 patients). Most of the patients (96%)
      exhibited recordable baseline MEPs. Persistent MEP decreases of more than 50%
      were noted for eight patients (16%) (11 muscles). The MEPs were completely
      abolished in two patients (three muscles). The degree of postoperative worsening
      of motor status was correlated with the degree of intraoperative MEP amplitude
      reduction (r = -0.864; P < 0.001). CONCLUSION: Persistent intraoperative MEP
      reductions of more than 50% were associated with postoperative motor deficits.
      The degree of MEP amplitude reduction was correlated with postoperative worsening
      of motor status. Transcranial electrical MEP monitoring is feasible, safe, and
      valuable for brain tumor surgery.

PMID- 11334275
TI  - Intraoperative magnetic resonance imaging combined with neuronavigation: a new
      concept.
AB  - OBJECTIVE: Intraoperative image data may be used not only to evaluate the extent
      of a tumor resection but also to update neuronavigation, compensating for brain
      shift. To date, however, intraoperative magnetic resonance imaging (MRI) can be
      combined only with navigation microscopes that are separated from the magnetic
      field, thus requiring time-consuming intraoperative patient transport. To help
      solve this problem, we investigated whether a new navigation microscope can be
      used within the fringe field of the MRI scanner. METHODS: The navigation
      microscope was placed at the 5-G line of a 0.2 MRI device. Patients were
      positioned lying down directly on the table of the scanner, with their heads
      placed approximately 1.5 m from the center of the magnet, fixed in an MRI
      compatible ceramic head holder. Standard operating instruments were used. For
      intraoperative imaging, we slid the table into the center of the magnet in less
      than 30 seconds. RESULTS: By use of this setup, we operated on 22 patients. In
      all patients, anatomic neuronavigation could be used in combination with
      intraoperative MRI. In addition, in 12 patients, functional data from
      magnetoencephalographic or functional MRI studies were integrated, resulting in
      functional neuronavigation. We did not encounter adverse effects of the low
      magnetic field during navigation. Moreover, intraoperative imaging was not
      disturbed by the navigation microscope and vice versa. CONCLUSION: Functional
      neuronavigation and intraoperative MRI can be used essentially simultaneously
      without the need for lengthy intraoperative patient transport. The combination of
      intraoperative imaging with functional neuronavigation offers the opportunity for
      more radical resections and fewer complications.

PMID- 11334276
TI  - A phantom study of the geometric accuracy of computed tomographic and magnetic
      resonance imaging stereotactic localization with the Leksell stereotactic system.
AB  - OBJECTIVE: To assess the spatial accuracy of magnetic resonance imaging (MRI) and
      computed tomographic stereotactic localization with the Leksell stereotactic
      system. METHODS: The phantom was constructed in the shape of a box, 164 mm in
      each dimension, with three perpendicular arrays of solid acrylic rod, 5 mm in
      diameter and spaced 30 mm apart within the phantom. In this study, images from
      two different MRI scanners and a computed tomographic scanner were obtained using
      the same Leksell (Elekta Instruments, Stockholm, Sweden) head frame placement.
      The coordinates of the rod images in the three principal planes were measured by
      using a tool provided with Leksell GammaPlan software (Elekta Instruments,
      Norcross, GA) and were compared with the physical phantom measurements. RESULTS:
      The greatest distortion was found around the periphery, and the least distortion
      (<1.5 mm) was present in the middle and most other areas of the phantom. In the
      phantom study using computed tomography, the mean values of the maximum errors
      for the x, y, and z axes were 1.0 mm (range, 0.2-1.3 mm), 0.4 mm (range, 0.1-0.8
      mm), and 3.8 mm (range, 1.9-5.1 mm), respectively. The mean values of the maximum
      errors when using the Philips MRI scanner (Philips Medical Systems, Shelton, CT)
      were 0.9 mm (range, 0.4-1.7 mm), 0.2 mm (range, 0.0-0.7 mm), and 1.9 mm (range,
      1.3-2.3 mm), respectively. Using the Siemens MRI scanner (Siemens Medical
      Systems, New York, NY), these values were 0.4 mm (range, 0.0-0.7 mm), 0.6 mm
      (range, 0.0-1.0 mm), and 1.6 mm (range, 0.8-2.0 mm), respectively. The geometric
      accuracy of the MRI scans when using the Siemens scanner was greatly improved
      after the implementation of a new software patch provided by the manufacturer.
      The accuracy also varied with the direction of phase encoding. CONCLUSION: The
      accuracy of target localization for most intracranial lesions during stereotactic
      radiosurgery can be achieved within the size of a voxel, especially by using the
      Siemens MRI scanner at current specifications and with a new software patch.
      However, caution is warranted when imaging peripheral lesions, where the
      distortion is greatest.

PMID- 11334277
TI  - Novel magnetic technology for intraoperative intracranial frameless navigation:
      in vivo and in vitro results.
AB  - OBJECTIVE: To characterize the accuracy of the Magellan electromagnetic
      navigation system (Biosense Webster, Tirat HaCarmel, Israel) and to demonstrate
      the feasibility of its use in image-guided neurosurgical applications.
      DESCRIPTION OF INSTRUMENTATION: The Magellan system was developed to provide real
      time tracking of the distal tips of flexible catheters, steerable endoscopes, and
      other surgical instruments, using ultra-low electromagnetic fields and a novel
      miniature position sensor for image-correlated intraoperative navigation and
      mapping applications. METHODS: An image registration procedure was performed, and
      static and qualitative accuracies were assessed in a series of phantom, animal,
      and human neurosurgical studies. EXPERIENCE AND RESULTS: During the human study
      phase, an accuracy error of up to 5 mm was deemed acceptable. Results
      demonstrated that this degree of accuracy was maintained throughout all
      procedures. All anatomic landmarks were reached with precision and were
      accurately viewed on the display screen. Navigation that relied on the system was
      also successful. No interference with operating room equipment was noted. The
      accuracy of the system was maintained during regular surgical procedures, using
      standard surgical tools. CONCLUSION: The system provides precise lesion
      localization without limiting the line of vision, the mobility of the surgeon, or
      the flexibility of instruments. Electromagnetic navigation promises new advances
      in neuronavigation and frameless stereotactic surgery.

PMID- 11334278
TI  - Treating stroke as a medical emergency: a survey of resident physicians'
      attitudes toward "brain attack" and carotid endarterectomy.
AB  - OBJECTIVE: A major impetus of the "brain attack" campaign is the early
      recognition and treatment of acute stroke. Critical to this goal is the education
      of physicians during their residency training. METHODS: Resident physicians in
      Los Angeles who were in family practice (18%), internal medicine (51%), emergency
      medicine (20%), and neurology (11%) and had already completed their first year of
      training responded to a questionnaire on stroke and the treatment of carotid
      stenosis. RESULTS: Of the 266 respondents, 76% had heard of the "brain attack"
      campaign, 22% did not identify dysarthria as a symptom of stroke, and 21% did not
      identify obtundation as a presentation of stroke. Twenty-eight percent chose not
      to use tissue plasminogen activator for acute ischemic stroke, and 60% recognized
      the need to begin treatment within 3 hours. More than 90% of respondents were
      able to identify correct screening tests for patients with suspected carotid
      stenosis. However, 56% responded that they would not advocate operating on
      patients with asymptomatic severe stenosis (>70%) until stenosis reached a
      critical value (85%). Conversely, 45% would recommend operative treatment for
      symptomatic patients who had less than 60% stenosis. Sixty-eight percent would
      refer patients to vascular surgeons, 14% to neurosurgeons, and 17% to both for
      carotid endarterectomy. CONCLUSION: Recognition of stroke as a medical emergency
      is improving. However, significant progress can still be made in the recognition
      of stroke symptoms. Primary care and neurology residents remain skeptical about
      carotid endarterectomy for asymptomatic patients, whereas there is enthusiasm for
      treating stroke survivors. Education by members of the surgical community could
      promote the aggressive treatment of asymptomatic patients to prevent stroke.

PMID- 11334279
TI  - The effect of groups II and III metabotropic glutamate receptor activation on
      neuronal injury in a rodent model of traumatic brain injury.
AB  - OBJECTIVE: The role of metabotropic glutamate receptor activation after traumatic
      brain injury (TBI) is not well understood. In vitro studies suggest that
      activation of Groups II and III metabotropic glutamate receptors may provide some
      degree of neuroprotection and may be potential targets for the development of
      therapeutic strategies. Thus, we examined the effects of Group II and Group III
      selective agonists on neuronal degeneration after in vivo TBI. METHODS: Fifty
      male Sprague-Dawley rats were subjected to lateral fluid percussion brain injury
      immediately followed by an intracranial injection of 2-(2',3')
      dicarboxycyclopropylglycine (DCG-IV) (Group II) or (R,S)-4-phosphonophenylglycine
      (Group III) in the CA2 and CA3 areas of the hippocampus. DCG-IV was injected at
      doses of 20 fmol, 100 fmol, and 500 fmol, and (R,S)-4-phosphonophenylglycine was
      injected at 8 nmol, 40 nmol, and 200 nmol. Vehicle injection control groups were
      used for comparison with each drug group. All animals were killed 24 hours after
      TBI was induced. Four 50-microm brain sections were obtained from each animal and
      stained for degenerating neurons with the fluorochrome Fluoro-Jade. Two
      independent, blinded investigators counted the number of degenerating (Fluoro
      Jade-positive) neurons in the CA2 and CA3 areas of the hippocampus of each brain
      section. RESULTS: Compared with vehicle, the 500-fmol dose of DCG-IV
      significantly reduced the number of Fluoro-Jade-positive degenerating neurons (P
      < 0.001). Lower doses of DCG-IV were associated with a decreased but not
      statistically significant number of Fluoro-Jade-positive neurons. In contrast,
      (R,S)-4-phosphonophenylglycine had no significant effect on the number of
      degenerating neurons. CONCLUSION: Administration of selective Group II
      metabotropic glutamate receptor agonists protects neurons against in vivo TBI.
      These receptors may thus be a promising target for future neuroprotective drugs.

PMID- 11334280
TI  - Effect of moderate hypothermia on experimental severe subarachnoid hemorrhage, as
      evaluated by apparent diffusion coefficient changes.
AB  - OBJECTIVE: The aims of this study were to investigate the early changes in the
      mean apparent diffusion coefficient (ADC) after severe subarachnoid hemorrhage
      (SAH), as a marker of ischemic damage, and to examine the effects of moderate
      hypothermia, induced at various time points, on ADC changes. METHODS: ADC maps
      were calculated from diffusion-weighted, blipped-epi, spin echo, magnetic
      resonance imaging sequences (2.35-T BIOSPEC 24/40 scanner; Bruker Medizin Technik
      GmbH, Karlsruhe, Germany) for 21 anesthetized (0.45-1% halothane, temperature
      adjusted/30% oxygen/69% nitrogen) and ventilated Wistar rats. After baseline
      scanning, bolus injection of 0.5 ml of autologous arterial blood or artificial
      cerebrospinal fluid (control group), into the cisterna magna, was performed.
      Serial scanning was performed for 3 hours after injection, using normothermic or
      hypothermic (32 degrees C) rats. In an additional series of experiments,
      hypothermia was initiated either immediately or 60 minutes after normothermic
      SAH. The water contents of the removed brains were calculated using the wet/dry
      weight method. RESULTS: The ADC values did not change in the control group but
      decreased to 88.6+/-5.2% (P < 0.05 versus baseline) after SAH and remained
      significantly decreased throughout the experiment in normothermia. An injection
      of blood during hypothermia caused an initial decrease in ADC to 96.1+/-5.6% (P <
      0.05 versus baseline); values continuously increased and reached normal levels
      within 60 minutes. Delayed hypothermia also normalized ADC values within the
      observation period. The brain water content in the control group was 80.3+/-0.1%,
      that after SAH in normothermia was 81.1+/-0.7%, and that after SAH in hypothermia
      was 79.3+/-0.5%. CONCLUSION: This model of severe SAH in rats causes significant
      ADC changes, which are reversible by application of moderate hypothermia even
      when it is induced after a 60-minute delay. These findings support the concept of
      moderate hypothermia exerting a neuroprotective effect in severe SAH.

PMID- 11334281
TI  - Ultrasound accelerates functional recovery after peripheral nerve damage.
AB  - OBJECTIVE: Axonal injury in the peripheral nervous system is common, and often it
      is associated with severe long-term personal and societal costs. The objective of
      this study is to use an animal model to demonstrate that transcutaneous
      ultrasound can accelerate recovery from an axonotmetic injury. METHODS: The
      sciatic nerve of adult male Lewis rats was crushed in the right midthigh to cause
      complete distal degeneration of axons yet maintain continuity of the nerve.
      Beginning 3 days after surgery, various transcutaneous ultrasound treatments or
      sham treatments were applied 3 days per week for 30 days to the crush site of
      rats that were randomly assigned to two groups. In the preliminary experiments,
      there were three animals in each ultrasound group and two control animals. In the
      final experiment, there were 22 animals in the ultrasound group and 20 animals in
      the control group. Recovery was assessed by use of a toe spread assay to quantify
      a return to normal foot function in the injured leg. Equipment included a hand
      held transducer that emitted continuous-wave ultrasound. The most successful
      ultrasound protocol had a spatial peak, time-averaged intensity of 0.25 W/cm2
      operated at 2.25 MHz for 1 minute per application. RESULTS: Rats subjected to the
      most successful ultrasound protocol showed a statistically significant
      acceleration of foot function recovery starting 14 days after injury versus 18
      days for the control group. Full recovery by the ultrasound group occurred before
      full recovery by the control group. CONCLUSION: Transcutaneous ultrasound applied
      to an animal model of axonotmetic injury accelerated recovery. Future studies
      should focus on identification of the mechanism(s) by which ultrasound creates
      this effect, as a prelude to optimization of the protocol, demonstration of its
      safety, and its eventual application to humans.

PMID- 11334282
TI  - Olfaction preservation in anterior cranial base approaches: an anatomic study.
AB  - OBJECTIVE: To study the anatomic basis for olfaction-sparing anterior cranial
      base approaches. METHODS: The medial anterior skull base containing the olfactory
      unit and delimited by the inner table of the frontal sinus, the lesser wing of
      the sphenoid bone, and the medial orbital walls was removed from six cadaveric
      specimens. Histological methods were used to investigate the location,
      distribution, and depth of penetration of olfactory nerves. Hematoxylin and eosin
      and Gomori trichrome staining were used to visualize landmarks and architecture.
      S-100 neurofilament protein immunostaining was used to identify nerve fascicles
      and axons. In three cadaveric head specimens, olfaction-sparing craniofacial
      approaches were performed and the excised olfactory units were evaluated
      histologically. RESULTS: Bundles of olfactory nerves were identified primarily in
      the nasal septum; relatively fewer bundles could be identified in the middle
      turbinate. Olfactory nerve endings were identified up to 20 mm below the
      cribriform plate (range, 7-20 mm). The superior and middle nasal meatus were most
      innervated; olfactory innervation was virtually absent in the inferior nasal
      meatus. Histological evaluation of the olfactory unit elevated during olfaction
      sparing techniques routinely revealed transection of olfactory nerves that exited
      the skull base. CONCLUSION: In olfaction-sparing anterior cranial base
      approaches, the olfactory nerves are inevitably transected. The clinical
      significance of olfactory nerve transection for postoperative functional recovery
      of olfaction remains to be analyzed.

PMID- 11334283
TI  - Superficial siderosis associated with multiple cavernous malformations: report of
      three cases.
AB  - OBJECTIVE AND IMPORTANCE: Superficial siderosis is a rare but potentially
      devastating syndrome caused by recurrent subarachnoid hemorrhage. We present
      three cases of superficial siderosis associated with multiple cavernous
      malformations, and we review previous reports of superficial siderosis
      attributable to vascular malformations. CLINICAL PRESENTATION: Patients most
      commonly present with progressive sensorineural hearing loss, cerebellar ataxia,
      and pyramidal signs. Magnetic resonance imaging diagnosis may precede symptom
      development, however. In two of our cases, superficial siderosis was identified
      on magnetic resonance imaging scans in the absence of clinical symptoms.
      INTERVENTION: Magnetic resonance imaging studies revealed hemosiderin deposition,
      characteristic of superficial siderosis, and multiple cavernous malformations in
      all three cases. Surgical intervention was not pursued. CONCLUSION: We conclude
      that patients with multiple cavernous malformations and those with
      perisubarachnoid lesions are at risk for the development of superficial
      siderosis. Clinicians should recognize the radiographic appearance of superficial
      siderosis and its clinical presentation in patients with vascular malformations.

PMID- 11334284
TI  - Mycotic aneurysm of the carotid bifurcation in the neck: case report and review
      of the literature.
AB  - OBJECTIVE AND IMPORTANCE: Mycotic aneurysms of the extracranial carotid artery
      are rare and difficult to diagnose. A search of the world literature published
      since 1966 reveals at least six cases of mycotic carotid aneurysms due to a
      Salmonella septicemia. We present an exceptional case of mycotic pseudoaneurysm
      of the bifurcation of the carotid artery due to Salmonella septicemia and discuss
      the pathogenesis as well as various aspects of the diagnosis and surgical
      management. CLINICAL PRESENTATION: A 68-year-old man presented in Poland with
      Salmonella sepsis; 1 month later, he was admitted to the emergency department of
      the Sir Mortimer B. Davis-Jewish General Hospital in Montreal with a bulky and
      pulsatile right cervical mass. An angiogram and a computed tomographic scan
      revealed a voluminous and partially thrombosed aneurysm the size of a tangerine
      originating from the posterior aspect of the carotid junction. INTERVENTION:
      Balloon trapping was attempted at the Montreal Neurological Hospital.
      Subsequently, the patient developed a significant neurological deficit, which was
      quickly reversed by the administration of hypertensive, hypervolemic, and
      hemodilution therapy. Thereafter, the pseudoaneurysm was resected surgically, and
      the internal and external carotid arteries were sacrificed. Pathological
      examination of the excised specimen of the carotid junction revealed a
      pseudoaneurysm. Bacterial culture of the lesion showed growth of Salmonella.
      CONCLUSION: The postoperative course was satisfactory except for laryngeal
      paralysis due to involvement of the vagus nerve. Four months later, a computed
      tomographic scan showed only small lacunae in both centra semiovale.

PMID- 11334285
TI  - Clinical and neurophysiological observations after superior petrosal vein
      obstruction during surgery of the cerebellopontine angle: case report.
AB  - IMPORTANCE: Preservation of venous drainage during surgery of the
      cerebellopontine angle has received little attention. CLINICAL PRESENTATION: We
      describe changes in brainstem auditory evoked potentials after temporary
      obstruction of the superior petrosal vein during surgical resection of a small
      meningioma at the petrous apex via a standard suboccipital-lateral approach.
      Temporary clipping of the petrosal vein resulted in deterioration of the
      brainstem auditory evoked potentials. The tumor was removed with preservation of
      the superior petrosal vein. CONCLUSION: A transient postoperative cochlear nerve
      deficit emphasizes the importance of venous drainage and its preservation during
      surgery for small lesions of the cerebellopontine angle that do not distort
      normal anatomic structures.

PMID- 11334286
TI  - Adenocarcinoma of the salivary gland metastatic to the pituitary gland: case
      report.
AB  - OBJECTIVE AND IMPORTANCE: A case of metastasis to the pituitary gland from a
      ductal adenocarcinoma of the salivary gland is presented. Metastasis to this site
      is rare, and a salivary gland source has never previously been described.
      CLINICAL PRESENTATION: This patient presented with hypopituitarism, including
      diabetes insipidus. INTERVENTION: A craniotomy was performed to alleviate visual
      loss. The histological features of the sellar tumor were identical to those of a
      tumor removed from the parotid gland 18 months earlier. CONCLUSION: Although
      intrasellar tumors originating from embryonic rests of salivary gland tissue have
      been reported, metastasis from a malignant neoplasm arising within a true
      salivary gland is also possible and should not be excluded from consideration for
      patients in whom a salivary gland-like tumor is discovered in the sella turcica.

PMID- 11334287
TI  - Epithelioid hemangioendothelioma of the spine presenting as cervical myelopathy:
      case report.
AB  - OBJECTIVE AND IMPORTANCE: We report the first case in the literature of cervical
      myelopathy caused by progressive cord compression as a result of epithelioid
      hemangioendothelioma of the cervical vertebra. CLINICAL PRESENTATION: A 58-year
      old man presented with progressive cervical myelopathy. Imaging revealed a
      vascular, expansile lesion of contiguous cervical vertebrae causing cord
      compression. The surgical pathology revealed epithelioid hemangioendothelioma, a
      rare tumor not previously reported to present in such a fashion. INTERVENTION:
      Preoperative embolization and a two-stage anterior and posterior surgical
      decompression and fusion procedure were performed. The high vascularity of this
      lesion makes surgery a formidable surgical challenge. Adjuvant radiotherapy was
      administered to the residual tumor because of its potential for low-grade
      malignancy. CONCLUSION: The diagnosis relied on accurate histopathological
      assessment. The general principles of achieving cord decompression and tumor
      control are important. The literature on epithelioid hemangioendothelioma
      involving the spine is reviewed, and the tumor biology and the role of adjuvant
      therapy are discussed.

PMID- 11334288
TI  - Tophaceous gout of the spine mimicking epidural infection: case report and review
      of the literature.
AB  - OBJECTIVE AND IMPORTANCE: Tophaceous gout uncommonly affects the axial skeleton.
      The clinical presentations of gout of the spine range from back pain to
      quadriplegia. Gout that presents as back pain and fever may be difficult to
      distinguish from spinal infection. We present a case of a patient with tophaceous
      gout of the lumbar spine who was initially diagnosed with and treated for an
      epidural infection. The clinical and diagnostic features of tophaceous gout of
      the spine are reviewed. CLINICAL PRESENTATION: A 70-year-old man presented with a
      2-day history of fever and back pain. A physical examination revealed that he had
      flank tenderness and evidence of polyarthritis affecting the elbows, knees, and
      right first metatarsophalangeal joint. A magnetic resonance imaging scan of the
      patient's lumbar spine showed an extensive area of abnormal gadolinium
      enhancement of the paramedian posterior soft tissues from L3 to S1 with an area
      of focal enhancement extending into the right L4-L5 facet joint. INTERVENTION: A
      laminectomy was performed at L4-L5, and a chalky white material in the facet
      joint was found eroding into the adjacent pars intra-articularis. Light and
      polarizing microscopy confirmed the presence of gouty tophus. No evidence of
      infection was found. CONCLUSION: Gouty arthritis of the spine is rare. Thirty
      seven previous cases have been reported. When the clinical presentation includes
      acute back pain and fever, differentiation of spinal gout from spinal infection
      may be difficult. The clinical suspicion of spinal gout may lead to the correct
      diagnosis by a less invasive approach than exploration and laminectomy.

PMID- 11334289
TI  - Carotid endarterectomy with external shunt: a new device and indication for use:
      technical note.
AB  - OBJECTIVE: We designed a new external shunt system and evaluated its indications
      and efficacy in patients undergoing carotid endarterectomy (CEA). METHODS: In 8
      of 332 CEA procedures, external shunts were placed between the common carotid
      artery and the internal carotid artery (ICA). This procedure was implemented for
      one of two indications: 1) a change in electroencephalographic and/or
      somatosensory evoked potential readings immediately after ICA occlusion, or 2)
      elongation of the ICA made safe insertion of an internal shunt impossible. In
      addition, a shunt was placed between the common carotid artery and the external
      carotid artery to establish collateral circulation from the external carotid
      artery to the intracranial circulation, which is essential during ICA occlusion.
      RESULTS: All external shunts were functional, and electroencephalography and
      somatosensory evoked potentials demonstrated no significant abnormalities during
      the CEAs. All patients awoke from surgery without manifestation of new
      neurological deficits. CONCLUSION: Our new external shunt device proved safe and
      efficacious in cases that did not permit the placement of an internal shunt.

PMID- 11334291
TI  - Microcatheterization of the cervical epidural space via lumbar puncture:
      technical note.
AB  - OBJECTIVE: Deposition of opiates, corticosteroids, or local anesthetics into the
      epidural space is useful for the management of painful maladies of the cervical
      and thoracic spine. We describe a novel technique for epidural medication
      delivery via an angiographic microcatheter inserted at or below the conus and
      advanced cephalad under fluoroscopic guidance. Unlike commercial kits used by
      anesthesiologists, this method uses a radiopaque catheter that can be precisely
      targeted to the levels of interest. The hazards of direct puncture, such as "wet
      tap" or injury to the cervical cord, are minimized. METHODS: An 18-gauge Tuohy
      needle is inserted into the lumbar epidural space. A 2.3-French microcatheter and
      a 0.018-inch steerable guidewire are then introduced through the lumen of the
      needle. The catheter is fluoroscopically advanced to the cervical epidural space,
      where Depo-Medrol (Pharmacia & Upjohn, Kalamazoo, MI) is administered. As the
      catheter is withdrawn, additional corticosteroid can be delivered to the thoracic
      epidural space, together with long-acting morphine compounds or local
      anesthetics. Regional pressures within the epidural space and other physiological
      parameters can be measured, and the local microenvironment can be sampled.
      RESULTS: To date, we have performed 16 procedures for 13 patients. All patients
      reported improvement, of varying extent and duration. There have been no
      complications. CONCLUSION: Our system of accessing the epidural space has many
      advantages, compared with direct puncture and commercially available kits. It
      provides a safe means of delivering epidural medication to multiple spinal levels
      and permits measurement of physiological variables that may be useful in the
      diagnosis and treatment of cervical and thoracic spine disease.

PMID- 11334290
TI  - Multimodal cranial neuronavigation: direct integration of functional magnetic
      resonance imaging and positron emission tomography data: technical note.
AB  - OBJECTIVE: This is the first report of the direct integration of functional
      magnetic resonance imaging (fMRI) and positron emission tomography (PET) data
      into cranial neuronavigation. METHODS: In a patient with a left precentral
      oligodendroglioma (World Health Organization Grade III), the Zeiss MKM system
      (Carl Zeiss Co., Oberkochen, Germany) was used for navigation based on thin
      slice, T1-weighted, contrast-enhanced magnetic resonance imaging (MRI) scans.
      fMRI and methionine PET data were integrated by landmark matching, with reference
      to skin fiducials. RESULTS: The inaccuracy of the image fusion between fMRI and
      T1-weighted MRI data was 1.7 mm, that between PET and T1-weighted MRI data was
      4.3 mm, and that for the subsequent registration of the navigation was 1.2 mm.
      The correct fMRI localization of the precentral gyrus was intraoperatively
      verified by cortical somatosensory evoked potential (phase-reversal) monitoring.
      Although the tumor was not clearly defined in the MRI scans, [11C]methionine PET
      demonstrated a clear tumor border, enabling us to achieve gross total tumor
      removal without postoperative functional deficits. CONCLUSION: Functional
      neuronavigation permits observation and preservation of relevant brain areas.
      Other functional areas (such as short-term memory areas) that can be detected
      only by fMRI might also warrant future monitoring. The simultaneous integration
      of fMRI and PET data adds a new dimension to cranial neuronavigation, enabling
      the observation of tumors in relation to functional cortical areas (in our case,
      the motor strip).

PMID- 11334292
TI  - Scalp marking for a craniotomy using a laser pointer during preoperative computed
      tomographic imaging: technical note.

PMID- 11334293
TI  - Scalp marking for a craniotomy using a laser pointer during preoperative computed
      tomographic imaging: technical note.

PMID- 11334294
TI  - Modern neurosurgery for psychiatric disorders.

PMID- 11334295
TI  - Effects of the "special bomb": recollections of a neurosurgeon in Hiroshima,
      August 8-15, 1945.

PMID- 11334296
TI  - Effects of the "special bomb": recollections of a neurosurgeon in Hiroshima,
      August 8-15, 1945.

PMID- 11334297
TI  - The posterior cranial fossa: microsurgical anatomy and surgical approaches.

PMID- 11334298
TI  - Lower cognitive performance of older football players possessing apolipoprotein E
      epsilon4.

PMID- 11334299
TI  - Cerebral arteriovenous malformations: comparison of novel magnetic resonance
      angiographic techniques and conventional catheter angiography.
AB  - OBJECTIVE: To investigate the potential of novel magnetic resonance (MR)
      angiographic techniques for the assessment of cerebral arteriovenous
      malformations. METHODS: Forty patients who were about to undergo stereotactic
      radiosurgery were prospectively recruited. Three-dimensional, sliding-slab
      interleaved ky (SLINKY), time-of-flight acquisition was performed, as was a
      dynamic MR digital subtraction angiography (DSA) procedure in which single thick
      slices (6-10 cm) were obtained using a radiofrequency spoiled Fourier-acquired
      steady-state sequence (1 image/s). Sixty images were acquired, in two or three
      projections, during passage of a 6- to 10-ml bolus of gadolinium chelate.
      Subtraction and postprocessing were performed, and images were viewed in an
      inverted cine mode. SLINKY time-of-flight acquisition was repeated after the
      administration of gadolinium. Routine stereotactic conventional catheter
      angiography was performed after MR imaging. All images were assessed (in a
      blinded randomized manner) for Spetzler-Martin grading and determination of
      associated vascular pathological features. RESULTS: Forty-one arteriovenous
      malformations were assessed in 40 patients. Contrast-enhanced (CE) SLINKY MR
      angiography was the most consistent MR imaging technique, yielding a 95%
      correlation with the Spetzler-Martin classification defined by conventional
      catheter angiography; MR DSA exhibited 90% agreement, and SLINKY MR angiography
      exhibited 81% agreement. CE SLINKY MR angiography provided improved nidus
      delineation, compared with non-CE SLINKY MR angiography. Dynamic information from
      MR DSA significantly improved the observation of early-draining veins and
      associated aneurysms. CONCLUSION: CE SLINKY MR angiographic assessment of
      cerebral arteriovenous malformations offers significant advantages, compared with
      the use of non-CE SLINKY MR angiography, including improved nidus demonstration.
      MR DSA shows promise as a noninvasive method for dynamic angiography but is
      presently restricted by limitations in both temporal and spatial resolution.

PMID- 11334300
TI  - Embolization of arteriovenous malformations with Onyx: clinicopathological
      experience in 23 patients.
AB  - OBJECTIVE: To report our experience in treatment of arteriovenous malformations
      (AVMs) using a new liquid embolic agent, Onyx (Micro Therapeutics, Inc., Irvine,
      CA). METHODS: Between January 1998 and May 1999, 23 patients (8 men and 15 women)
      were treated. The patients' average age was 40 years, with seizure being the most
      common presenting symptom (39%). The average Spetzler-Martin grade on
      presentation was 3. The average AVM volume before embolization was 14.5 cm3.
      RESULTS: We observed an average 63% reduction in AVM volume after 129 arterial
      feeders were embolized. There were four adverse events. Two patients experienced
      ischemia because of inadvertent occlusion of an arterial feeder. One of these
      patients made a full recovery, but the other patient had a permanent deficit. Two
      other patients experienced transient neurological deficits that resolved within 1
      week of embolization. Permanent morbidity was thus 4% (1 of 23 patients). There
      were no deaths. Twelve patients underwent subsequent radiosurgery, and 11
      patients had surgery that resulted in complete resection of their AVMs.
      Histopathological examinations showed mild acute inflammation in specimens
      resected 1 day after embolization. Chronic inflammatory changes were observed in
      specimens resected more than 4 days after embolization. In two patients,
      angionecrosis of the embolized vessels was noted. No evidence of parenchymal
      hemorrhage was observed in these patients, and vessel wall integrity was
      maintained as well. CONCLUSION: Onyx is a new nonadhesive liquid embolic agent
      that has been used to treat 23 patients at our institution with good results. Its
      nonadhesive nature and ease of use make it a promising agent in the future
      treatment of AVMs.

PMID- 11334302
TI  - Year's comments for 2000.

PMID- 11334301
TI  - Open-label phase I clinical study to assess the safety of intravenous
      eptifibatide in patients undergoing internal carotid artery angioplasty and stent
      placement.
AB  - OBJECTIVE: Eptifibatide, a competitive platelet glycoprotein IIb-IIIa receptor
      inhibitor with high selectivity and a short half-life, has been demonstrated to
      reduce the risk of ischemic events associated with coronary interventions.
      However, its role in neurointerventional procedures needs to be analyzed. We
      report the results of an open-label Phase I study to evaluate the safety of the
      use of eptifibatide during carotid angioplasty and stent placement. METHODS: Each
      study patient received eptifibatide administered intravenously as a 135-microg/kg
      single-dose bolus, then a 0.5-microg/kg/min infusion for 20 to 24 hours during
      carotid angioplasty and stent placement. The primary efficacy end point was the
      30-day composite occurrence of death, cerebral infarction, transient ischemic
      attack, and unplanned or urgent surgical intervention, thrombolysis, or
      subsequent percutaneous revascularization. The primary safety end point was
      bleeding. Bleeding complications were classified as major (hemoglobin decrease >5
      g/dl), minor (hemoglobin decrease 3-5 g/dl), or insignificant. RESULTS: Ten
      patients (mean age, 73 yr; four men) were treated by use of the study protocol.
      One patient developed a minor stroke postprocedurally (National Institutes of
      Health Stroke Scale score of 21 at 24 h that improved to 1 at 7 d). Three
      patients underwent scheduled coronary artery bypass graft surgery 4 to 12 days
      after undergoing carotid angioplasty and stent placement. At 1-month follow-up,
      no new ischemic events were observed. Major or minor bleeding was not observed in
      any patient. Insignificant bleeding was observed in two patients. CONCLUSION: The
      use of eptifibatide as an adjunct to carotid angioplasty and stent placement
      seems to be safe. Further studies are required to analyze the effectiveness and
      role of eptifibatide in neurointerventional procedures.

PMID- 11334303
TI  - Developments in aquatic microbiology.
AB  - Major discoveries in marine microbiology over the past 4-5 decades have resulted
      in the recognition of bacteria as a major biomass component of marine food webs.
      Such discoveries include chemosynthetic activities in deep-ocean ecosystems,
      survival processes in oligotrophic waters, and the role of microorganisms in food
      webs coupled with symbiotic relationships and energy flow. Many discoveries can
      be attributed to innovative methodologies, including radioisotopes,
      immunofluorescent-epifluorescent analysis, and flow cytometry. The latter has
      shown the key role of marine viruses in marine system energetics. Studies of the
      components of the "microbial loop" have shown the significance of various
      phagotrophic processes involved in grazing by microinvertebrates. Microbial
      activities and dissolved organic carbon are closely coupled with the dynamics of
      fluctuating water masses. New biotechnological approaches and the use of
      molecular biology techniques still provide new and relevant information on the
      role of microorganisms in oceanic and estuarine environments. International
      interdisciplinary studies have explored ecological aspects of marine
      microorganisms and their significance in biocomplexity. Studies on the origins of
      both life and ecosystems now focus on microbiological processes in the marine
      environment. This paper describes earlier and recent discoveries in marine
      (aquatic) microbiology and the trends for future work, emphasizing improvements
      in methodology as major catalysts for the progress of this broadly-based field.

PMID- 11334304
TI  - Canaleparolina darwiniensis, gen. nov., sp. nov., and other pillotinaceous
      spirochetes from insects.
AB  - We describe two new pillotinaceous spirochetes (Canaleparolina darwiniensis,
      Diplocalyx cryptotermitidis) and identify for the first time Hollandina
      pterotermitidis from both the subterranean termite Cryptotermes cavifrons and the
      wood-eating cockroach Cryptocercus punctulatus based on morphometric analysis of
      transmission electron micrographic thin sections. C. darwiniensis, gen. nov., sp.
      nov., limited to near Darwin, Australia, invariably is present on the surface of
      the treponeme-studded trichomonad Mixotricha paradoxa, a consistent inhabitant of
      the hindgut of healthy termite Mastotermes darwiniensis. The spirochete both
      attached to the surface of protists and free-swimming in the paunch (hindgut)
      lumen of the insect has 16 periplasmic flagella (16:32:16) and imbricated wall
      structures that resemble flattened crenulations of Pillotina. The flagella
      surround half the protoplasmic cylinder. C. darwiniensis is the largest (0.5
      microm diameter x 25 microm length) of the three epibiotic bacteria (two
      spirochetes, one rod) that comprise the complex cortex of its host Mixotricha
      paradoxa. Several criteria distinguish Diplocalyx cryptotermitidis sp. nov.
      isolated from Cryptotermes cavifrons intestine: smaller diameter, fewer flagella,
      absence of inner and outer coats of the outer membrane, wider angle subtended by
      its flagella and, most notably, cytoplasmic tubule-associated centers, which are
      periodic electron dense spheres within the protoplasmic cylinder from which
      emanate cytoplasmic tubules up to 24 nm in diameter. This is also the first
      report of abundant populations of Hollandina in Cryptotermes cavifrons (those
      populations belong to the species H. pterotermitidis). Morphometric analysis of
      the first thin sections of any spirochetes (published nearly 40 years ago by A.V.
      Grimstone) permits us to identify the large (0.9 microm diameter) free-swimming
      intestinal symbiont of Cryptocercus punctulatus also as Hollandina
      pterotermitidis.

PMID- 11334305
TI  - Detection of Salmonella in food samples by the combination of immunomagnetic
      separation and PCR assay.
AB  - A combination of immunomagnetic separation and polymerase chain reaction (IMS
      PCR) was used to detect Salmonella in food samples. Pre-enrichment of samples was
      combined with filtration through a membrane for the removal of food debris. The
      IMS-PCR assay combines selective extraction of bacteria by specific antibodies
      with primer specific PCR amplification that enables to detect Salmonella in non
      fatty food samples in 24 h. In comparison with conventional cultural methods, the
      IMS-PCR is a rapid and specific method. Combined with filtration bags, it
      partially reduces the negative effects of the food matrix and allows the quick
      detection of Salmonella cells. The shortened protocols for Salmonella spp.
      detection described here can improve considerably current methodologies.

PMID- 11334306
TI  - Extracellular cyanobacterial substances inhibit microbial growth.
AB  - Cyanobacteria are able to produce extracellular substances with different
      biological activities and behaviors. The marine cyanobacteria Anabaena sp. strain
      Hi 26 and Oscillatoria subtilissima strain Bo 62 cause significant color changes
      in their growth media, while viscosity of the medium is influenced by Rivularia
      sp. strain Bo 85 and Oscillatoria limnetica strain Flo 1. Sterile-filtered media,
      pregrown with the organisms mentioned above, were used to study the influence of
      changes in media bioactivity induced by "excreted substances" on the growth
      and/or morphological development of five related filamentous cyanobacterial
      species and on selected heterotrophic microorganisms. Cell lysis, empty sheaths,
      different lengths of filaments, or even single cells and a decrease in
      chlorophyll a and protein content were the characteristic changes obtained by
      such a "cyanobacterial assay." The use of a "precultured" medium, as demonstrated
      in an "agar diffusion assay," affects in varying degrees the growth of gram
      positive and gram-negative heterotrophic bacteria, as well as of the yeast
      Saccharomyces cerevisiae.

PMID- 11334307
TI  - Rapid and low-level toxic PCR-based method for routine identification of
      Flavobacterium psychrophilum.
AB  - We describe a rapid, low-toxicity and simple method for the detection of the
      bacterial fish pathogen Flavobacterium psychrophilum. The method, based on the
      polymerase chain reaction (PCR), combined the electrophoresis of PCR products in
      a vertical agarose gel and a modified methylene blue stain. DNA was amplified
      directly either from bacterial suspensions or from tissues experimentally
      infected with F. psychrophilum, using different non-toxic commercial DNA
      extraction kits. The protocol allowed to detect 15 to 150 cells of the pathogen
      in bacterial suspension, without prior DNA extraction, and 7500 to 75,000 cells
      in seeded spleen tissue and ovarian fluid using Dynabeads DNA DIRECT extraction
      system. This method, which has the advantage of not using hazardous products, is
      proposed as a fast tool for routine identification of F. psychrophilum.

PMID- 11334308
TI  - The purified colicin S8 is a multimeric protein.
AB  - Bacteriocins have been isolated both as simple proteins and as proteins in
      association with carbohydrates, lipids, etc. Colicins are commonly inducible and
      extracellular. Their molecular masses range from 30 to 90 kDa. Pure colicin S8
      was obtained in three steps from supernatant of induced cells: (i) Ammonium
      sulfate precipitation; (ii) anion exchange chromatography; and (iii) phenyl
      Sepharose hydrophobic chromatography, either by preparative or fast performance
      liquid chromatography (FPLC) analytical purification procedure. In our hands,
      purified colicin S8 was an aggregation of extremely related polypeptides.
      Composition of those active fractions was the same: five polypeptides of
      molecular weight around 55 kDa. Behavior on molecular filtration indicated a
      molecular weight higher than 200 kDa. Similar results were obtained when
      purification was carried out through FPLC. Producing strains contain a single
      plasmid that encodes colicin S8; in minicells, this plasmid was shown to specify
      a 60 kDa polypeptide. We conclude that more than one form of colicin S8 exists.
      The forms are structurally related and can be recognized by antibodies raised
      against one of the polypeptides. Consistent with this conclusion, comparison of
      peptides produced after hydrolysis with chlorosuccinamide indicated that the
      active proteins contained both shared and unique components.

PMID- 11334309
TI  - Candida albicans molecular biology reaches its maturity.

PMID- 11334310
TI  - Help for editors: EASE makes things easier. European Association of Science
      Editors.

PMID- 11334311
TI  - Elevated vascular endothelial growth factor levels in the urine of patients with
      minimal-change nephrotic syndrome.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) is a selective endothelial
      mitogen and vascular permeability factor (VPF), that is mainly produced by
      activated monocytes/macrophages and T cells. To our knowledge, very little is
      known about the involvement of VEGF in minimal-change nephrotic syndrome (MCNS).
      The aim here was to define further the involvement of VEGF in MCNS. PATIENTS AND
      METHODS: Urine samples were obtained from 20 MCNS patients. The disease controls
      included 20 patients with IgA nephropathy (IgAN). The samples were assayed for
      VEGF protein by a sandwich enzyme-linked immunosorbent assay (ELISA). RESULTS:
      Compared with normal controls, markedly increased urinary levels of VEGF were
      detected in both MCNS and IgAN patients with the nephrotic syndrome (NS). The
      urinary VEGF (uVEGF) levels correlated with the degree ofproteinuria in MCNS and
      IgAN patients. Moreover, when individual MCNS patients were followed through
      their clinical illness, uVEGF levels were increased during the active phase and
      decreased as the patients went into remission. Our main concern is to distinguish
      between two possibilities: Increases in uVEGF excretion might indeed relate to
      specific glomerular pathology and thus have a pathophysiological role.
      Alternatively, uVEGF may be derived from the circulation and as such may be
      nothing more than an assay for proteinuria. In fact, given the strict correlation
      between uVEGF excretion and the amount of proteinuria, the second possibility
      appears quite conceivable. CONCLUSION: Therefore, this may be a coincidental
      finding which has no bearing on the pathophysiology of MCNS.

PMID- 11334312
TI  - Evaluation of prognostic factors for myeloperoxidase anti-neutrophil cytoplasmic
      antibody- (MPO-ANCA) associated glomerulonephritis.
AB  - AIMS: To identify prognostic factors for myeloperoxidase anti-neutrophil
      cytoplasmic antibody- (MPO-ANCA) associated glomerulonephritis. MATERIALS: We
      analyzed the relations between the clinical and histological features of MPO-ANCA
      associated glomerulonephritis and clinical outcome in 14 patients with the
      disease. The patients were divided into two groups: group 1 consisted of 5
      patients with progressive deterioration of renal function leading to end-stage
      renal disease or chronic dialysis, group 2 consisted of 9 patients in whom the
      initial deterioration of renal function had improved by the time of the final
      examination. RESULTS: Creatinine clearance at the time of biopsy was
      significantly lower in group 1 than in group 2, and urinary protein was higher.
      The mean interval between onset of symptoms and biopsy in both groups was almost
      the same. Recovery of renal function was correlated with the percentage of global
      sclerosis, but patients who had severe crescent formation did not always have a
      poor response to steroid therapy. There was no statistical difference between the
      two groups in treatment regimens. Four patients required hemodialysis at the time
      of biopsy (3 in group 1 and 1 in group 2). Plasmapheresis was performed in 5
      patients (1 in group 1 and 4 in group 2). CONCLUSIONS: Degree of proteinuria and
      renal dysfunction are indicators of a poor prognosis in MPO-ANCA-associated
      glomerulonephritis. Global sclerosis is a histological feature that is an
      indicator of a poor prognosis, whereas cellular crescent formation is a predictor
      of a good response to steroid therapy.

PMID- 11334313
TI  - Diffuse alveolar hemorrhage in lupus nephritis.
AB  - AIM: Diffuse alveolar hemorrhage (DAH) is a rare and catastrophic event in
      systemic lupus erythematosus (SLE) with a high mortality rate, and little
      information is available about the degree of renal involvement in this condition.
      PATIENTS AND METHODS: To evaluate the effects of renal impairment on the course
      of DAH, the hospital records of 7 patients (9 episodes) with DAH and SLE between
      1988 and 1998 at Seoul National University Hospital were reviewed. A diagnosis of
      DAH was established when the patient had an acute pulmonary syndrome including
      either hemoptysis, new alveolar infiltrates on the chest radiograph, the presence
      of a falling hematocrit or hemorrhagic BAL. All patients were women and their
      median age was 26 years ranging between 23 and 39. All patients had concurrent
      lupus nephritis and 4 of them were classified as WHO class IV with renal
      pathology. RESULTS: Their median serum creatinine level at the time of DAH was
      4.6 mg/dl (0.8 - 13.6), and the median daily proteinuria amount was 778 mg (436 -
      6200). All of the patients received corticosteroid therapy, and intravenous
      cyclophosphamide was given to 3 cases. Hemodialysis was done in 3 cases, and 4 of
      the 7 patients died during an acute event. We reviewed five series about the
      clinical parameters, including the serum creatinine level, treatment and hospital
      outcome. From the results of the analysis, it was determined that concomitant
      infection (RR 4.2) and the use of mechanical ventilation (RR 6.1) were associated
      with the increased risk of mortality, but azotemia (sCr > 3.0 mg/dl) (RR 1.5) or
      hemodialysis therapy (RR 1.3) was not shown to have a significant association.
      CONCLUSION: It could be suggested that even though renal failure is combined with
      DAH in SLE patients, the same aggressive treatment results in a comparable
      outcome as patients with normal renal function.

PMID- 11334314
TI  - Glomerular growth under cyclosporine treatment in childhood nephrotic syndrome.
AB  - BACKGROUND: Glomerular hypertrophy is important in children with idiopathic
      nephrotic syndrome in regard to diagnosis and pathogenesis. Moreover, glomerular
      growth may be altered by cyclosporine (CsA) treatment in these patients. METHODS:
      Bowman's area (BA) and the glomerular tuft area (GA) of pre- and post-treatment
      biopsies was measured by morphometry in 47 children with idiopathic nephrotic
      syndrome (39 MCD and 8 FSGS) treated with CsA and low-dose prednisolone for up to
      2 years. RESULTS: BA and GA increased with age. The mean BA and GA were 1.2 times
      larger in FSGS than in MCD and the proportional increase was similar in both
      diseases after treatment. BA and GA decreased in 48.9% and 40.4% of cases after
      treatment, respectively, whereas tubulointerstitial lesion (TIL) developed in
      27.7%. BA and GA decreased to 10.4% and 8.3%, respectively in children who
      developed TIL after treatment and the values were largely unchanged in those
      treated for more than 16 months. CONCLUSIONS: Glomerular growth is hampered by
      CsA nephrotoxicity, which is a more common complication than TIL. The impairment
      of glomerular growth is related to the duration of treatment and the development
      of TIL, but not to age or diagnosis.

PMID- 11334315
TI  - Isolated sarcoid granulomatous interstitial nephritis: review of five cases at
      one center.
AB  - AIMS: To identify any clinical or biochemical parameters which determine
      prognostic outcome in isolated sarcoid granulomatous interstitial nephritis
      presenting with renal failure. METHODS: A review of five cases of renal failure
      due to isolated sarcoid granulomatous interstitial nephritis, which presented to
      Hope Hospital over the 7-year period 1994 to 2000. Follow-up averaged 35 months
      with a range of 11 to 73 months. RESULTS: Only one patient had an elevated serum
      ACE at presentation, reflecting the suboptimal sensitivity of this test as a
      marker in sarcoidosis and the limited extent of disease in these patients. Four
      of the five cases had a marked improvement in creatinine clearance within 10 days
      of starting oral prednisolone. Two patients required acute hemodialysis on
      presentation. Their renal failure responded to treatment with steroids, enabling
      withdrawal of dialysis within 10 days. All patients remained dialysis-independent
      although serum creatinine levels rose during follow-up. One patient experienced a
      relapse that responded to an increased dose of steroid. CONCLUSIONS: Serum ACE is
      not reliable in the diagnosis of renal failure due to sarcoid interstitial
      nephritis and the diagnosis can only be made on renal biopsy. First-line
      treatment with oral prednisolone results in a rapid improvement in creatinine
      clearance although prolonged treatment may be needed to prevent a relapse.

PMID- 11334316
TI  - Arterial distensibility and pulse wave velocity in patients with primary
      hyperparathyroidism before and after parathyroidectomy.
AB  - AIMS: There is evidence that secondary hyperparathyroidism alters arterial vessel
      wall properties. However, it is unclear whether effects of parathyroid hormone
      (PTH) on the vascular wall are direct or permissive and related to hypertension
      and renal failure. To assess early direct effects of PTH on large artery wall
      properties isobaric distensibility (DC), pulse wave velocity (PWV) and intima
      media thickness (IMT) were studied before and after parathyroidectomy (Ptx) in
      patients with primary hyperparathyroidism (pHPT). METHODS: DC and IMT of the
      brachial and carotid artery were measured by echo-tracking and tonometry, PWV by
      the automatic Complior-device at baseline and 6 months after Ptx in 20 patients
      with pHPT (data mean +/- SEM, age 45+/-5 years, PTH 240+/-61 ng/l).
      Cardiovascular risk factors like diabetes, hypertension, renal insufficiency and
      hypercholesterolemia were excluded. Twenty healthy volunteers matched for age,
      sex and blood pressure served as controls. RESULTS: Six months after Ptx, PTH
      decreased to normal; however, blood pressure levels and vessel wall parameter
      remained unchanged. At baseline, there were no significant differences in
      brachial and carotid IMT (0.48+/-0.04 and 0.62+/-0.04 mm vs. 0.47+/-0.06 and
      0.61+/-0.06 mm), radial and aortic PWV (9.1+/-0.4 and 9.9+/-0.7 m/s vs. 9.2+/-0.5
      and 10.0+/-0.6 m/s), brachial and isobaric carotid DC (10.1+/-1.4 and 19.5+/-3.4
      10(-3)/kPa vs. 9.1+/-0.9 and 20.4+/-3.2 10(-3)/kPa) or artery diameter between
      patients and controls. CONCLUSIONS: Structural and viscoelastic properties of
      large arteries are not disturbed and not influenced by parathyroidectomy in
      patients with early pHPT devoid of hypertension and renal disease. We conclude
      that increased PTH levels per se are not associated with alterations of
      mechanical arteriall wall properties; permissive factors like renal insufficiency
      may be necessary to mediate vessel wall alterations in patients with
      hyperparathyroidism.

PMID- 11334317
TI  - Living related renal transplantation--the use of advanced age donors.
AB  - AIM: Efforts to increase the donor pool and available organs included some
      unconventional kidney transplantation. One of these was including elderly donors
      for both, living and cadaver kidney transplantation. The aim of the study was to
      review our single centre experience with living donor transplants from elderly
      advanced age donors. PATIENTS AND METHODS: During a period of 7 years, 71 living
      related renal transplantations were performed. Twenty-six of them were over 65
      (mean 69+/-4, range 65 to 81), but 10 were over 70 years of age. The survival
      rate was compared with 45 transplants from younger donors (mean age 51+/-6, range
      24 to 59). The cold and warm ischemia time, the preservation procedure and blood
      vessels anastomosis time were comparable in both donor groups. The
      immunosuppression included sequental quadruple protocol with ATG, PRED, AZA and
      CyA replacing ATG after 7 days. The triple drug (AZA, PRED, CyA) maintenance
      therapy was applied to all recipients. RESULTS: Kaplan-Meier 1-, 3- and 5-year
      graft survival was 88.0%, 79.2% and 68%, respectively, for advanced donor age
      group and 90.2%, 82.4% and 74%, respectively, for younger donor group. The
      difference was slightly statistically significant (p < 0.05). In 6 patients who
      received graft from elderly donors, a delayed graft function was observed,
      whereas only in one in the younger donor group. CONCLUSION: Despite the worse
      results in the elderly donors' transplants, we consider the advanced age donors
      as an important source of kidneys contributing to solving the actual organ
      shortage, especially in our region.

PMID- 11334318
TI  - Homocysteine, vitamin B12, serum and erythrocyte folate in peritoneal dialysis
      patients.
AB  - Plasma homocysteine (tHcy) is an important risk factor for atherosclerosis in
      dialysis patients. Few data were reported on the prevalence and severity of
      hyperhomocysteinemia in peritoneal dialysis (PD) patients. In addition, little
      attention was paid to the search of factors possibly involved in the pathogenesis
      of hyperhomocysteinemia in these patients. A cross-sectional study was performed
      in 107 stable PD patients. None of them was given folate or vitamin B12
      supplementation before or during the study. Plasma tHcy, serum vitamin B12, serum
      and erythrocyte folate were measured by immunoenzymatic methods. Genetic analysis
      of the methylentetrahydrofolate-reductase thermolabile mutation (tMTHFR) was
      performed in 61 patients. 97% of patients had tHcy levels higher than normal.
      tHcy was not different between men and women, patients with or without
      malnutrition, with or without clinically evident atherosclerotic vasculopathy,
      with or without anemia. tHcy levels were significantly higher in homozygotes for
      the tMTHFR mutation than in patients carrying the wild type form. Significant
      univariate correlation was found between hyperhomocysteinemia and time since the
      start of dialysis, serum and erythrocyte folate and vitamin B12. The best fitted
      model equation was log tHcy = 108.53 + 0.1606 (duration of dialysis) -1.1053 (s
      F) -0.7980 (age) 0.0215 (vitamin B12). Our results agree with those reported by
      other authors in hemodialysis patients. Despite the large number of PD patients
      with normal serum vitamin B12 and folate status, the relation between tHcy and
      vitamin B12 or folate suggests that the supplementation of these vitamins could
      be useful irrespective of their serum levels, especially in younger patients or
      in those treated for a long period of time with peritoneal dialysis.

PMID- 11334319
TI  - Mycophenolate mofetil therapy for children with lupus nephritis refractory to
      both intravenous cyclosphosphamide and cyclosporine.
AB  - We describe mycophenolate mofetil (MMF), a new immunosuppressive agent, to be a
      therapy of two children with lupus nephritis which were refractory to both
      cyclophosphamide (CyP) and cyclosporine (CsA). After 11- to 12-month course of
      MMF treatment, all clinical symptoms of lupus disappeared and serum antibodies
      became negative. MMF might be a promising curative for cyclophosphamide-resistant
      lupus nephritis in children. Cyclophosphamide intravenous bolus therapy is
      generally considered to be the treatment for patients with lupus nephritis.
      However, there is little guidance about what to do if such therapy fails.
      Recently, a new immunosuppressive agent, mycophenolate mofetil (MMF), has been
      used to treat cyclophosphamide-resistant lupus nephritis [Dooley et al. 1999,
      Gaubitz et al. 1999, Glicklich and Acharga 1998] in adults and has been
      recognized as a promising curative for lupus nephritis. Up to now, MMF has been
      adopted widely with solid organ transplantation to prevent or reverse acute
      rejection [Mathew 1998, Morris-Stiff and Jurewicz 1998] and has been used
      successfully to treat for rheumatoid arthritis refractory to a variety of other
      drugs. But there is no report about MMF treatment in children with
      cyclophosphamide-resistant lupus nephritis. We describe our experience with MMF
      treatment in two Chinese children with lupus nephritis that were refractory not
      only to cyclophosphamide but also to cyclosporine.

PMID- 11334320
TI  - Renovascular hypertension associated with neurofibromatosis: two cases and review
      of the literature.
AB  - The authors report two cases of renovascular hypertension associated with
      neurofibromatosis. A 19-year-old woman was admitted to our hospital with a
      complaint of abdominal pain and blood pressure of 180/120 mmHg. Examination
      revealed cafe-au-lait spots over her chest and extremities. Peripheral plasma
      renin activity (PRA) under basal conditions was 2.8 ng/ml/h and increased to 12.6
      ng/ml/h after administration of 50 mg captopril. Plasma and urinary
      catecholamines were normal. Selective renal angiography showed left aneurysmal
      dilatation of the segmentary branch and right renal artery stenosis with multiple
      aneurysmal affecting different branches. Blood pressure was controlled by
      multiple drugs, including beta-blockers and angiotensin-converting enzyme
      inhibitor. Another patient, a 20-year-old woman, was admitted because of severe
      arterial hypertension, numerous cafe-au-lait spots, scoliosis, and mass over the
      right arm. PRA from the right renal vein was extremely elevated, and selective
      angiography demonstrated bilateral renal artery stenosis. Aortorenal bypass was
      performed successfully.

PMID- 11334321
TI  - Hypercalcemia and human nature.
AB  - Patients on hemodialysis may develop severe and symptomatic hypercalcemia if
      skeletal buffering is ineffective. We report a case of persistent hypercalcemia
      with apparent extrarenal vitamin D synthesis. Associated aluminium intoxication
      was suggested on desferrioxamine challenge and adynamic uremic osteodystrophy
      confirmed on bone biopsy. Plasma calcitriol did not suppress with corticosteroids
      but did with ketoconazole. No other evidence for underlying granulomatous disease
      was found. We discuss our approach to less usual causes of hypercalcemia, and
      emphasise the pitfalls associated with factitious disorders.

PMID- 11334322
TI  - Right-sided non-bacterial thrombotic endocarditis in a chronic hemodialysis
      patient with Muir-Torre syndrome.
AB  - Endocarditis is a recognised complication ofhemodialysis. This is generally only
      thought of in terms of infective vegetations. We present a case of right-sided
      NBTE in a patient with an indwelling venous catheter who also had advanced pelvic
      malignancy. The unusual side of this patient's endocarditic lesions implicates a
      role for the venous catheter in determining the site of non-bacterial thrombus
      formation. It is also a reminder that endocarditis is always a risk when using
      central venous catheters, even after appropriate sterile precautions have been
      taken.

PMID- 11334323
TI  - Prevalence of transfusion-transmitted virus (TTV) in patients with primary
      glomerulopathies.

PMID- 11334324
TI  - Rhabdomyolysis due to carbon monoxide poisoning.

PMID- 11334325
TI  - Myeloperoxidase anti-neutrophil cytoplasmic autoantibodies (MPO-ANCA)-related
      rapidly progressive glomerulonephritis (RPGN) and pulmonary fibrosis (PF) with
      dissociated evolution.

PMID- 11334326
TI  - Interaction between cyclosporine and acenocoumarol in a patient with nephrotic
      syndrome.

PMID- 11334328
TI  - RPA position on the role of non-physician medical personnel in delivering
      nephrologic care. Part 2 of 3.

PMID- 11334327
TI  - Unilateral renal agenesis and hypogonadotropic hypogonadism: an interesting
      coincidence.

PMID- 11334329
TI  - Sensitive determination of vinorelbine and its metabolites in human serum using
      liquid chromatography-electrospray mass spectrometry.
AB  - A liquid chromatography-electrospray mass spectrometry method was developed for
      the quantitation of vinorelbine (VNB) and two metabolites, vinorelbine N-oxide
      (VNO) and deacetyl vinorelbine (DAV) in human serum. The limits of quantitation
      (LOQ) reached 0.5 ng/ml for both VNB and VNO and 1 ng/ml for DAV. The method was
      proved linear in the range of LOQs up to 1000 ng/ml, and extraction recovery was
      80% on average for the three compounds. It was applied to the pharmacokinetic
      monitoring of vinorelbine and, for the first time, to the detection of VNO in the
      serum of patients suffering from non-small-cell lung cancer.

PMID- 11334330
TI  - Measurement of nicotine in hair by reversed-phase high-performance liquid
      chromatography with electrochemical detection.
AB  - We have developed an assay for nicotine in hair based on reversed-phase HPLC with
      electrochemical detection. The method uses a low-metal, high-purity silica
      reversed-phase column. We have investigated the washing, digestion and extraction
      procedures and discuss the important points in the HPLC method development. The
      assay is presented as an application in a population of exposed and non-exposed
      children. Analytical parameters are satisfactory with linearity, recoveries,
      limit of quantitation and precision all suitable for epidemiological studies
      involving environmental tobacco smoke exposure assessment.

PMID- 11334331
TI  - Identification and quantification of five macrolide antibiotics in several
      tissues, eggs and milk by liquid chromatography-electrospray tandem mass
      spectrometry.
AB  - We present an electrospray high-performance liquid chromatographic tandem mass
      spectrometric (HPLC-MS-MS) method capable of determining in several tissues
      (muscle, kidney, liver), eggs and milk the following five macrolides: tylosin,
      tilmicosin, spiramycin, josamycin, erythromycin. Roxithromycin was used as an
      internal standard. The method uses extraction in a Tris buffer at pH 10.5,
      followed by protein precipitation with sodium tungstate and clean-up on an Oasis
      solid-phase extraction column. The HPLC separation was performed on a Purospher
      C18 column (125 x 3 mm I.D.) protected by a guard column, with a gradient of
      aqueous 0.1 M ammonium acetate-acetonitrile as the mobile phase at a flow-rate of
      0.7 ml min(-1). Protonated molecules served as precursor ions for electrospray
      ionisation in the positive ion mode and four product ions were chosen for each
      analyte for multiple reaction monitoring (MRM). A validation study was conducted
      to confirm the five macrolides by MRM HPLC-MS-MS analysis of a negative control
      and fortified samples. All of the samples analysed were confirmed with four ions.
      The ion ratio reproducibility limit ranged from 2.4 to 15%. All compounds could
      be detected and quantified at half-maximum residue limits (MRLs). The method is
      specific, quantitative and reproducible enough to conform to European Union
      recommendations within the concentration range 0.5 MRL-2 MRL (accuracy: 80 to
      110%, relative standard deviation: 2 to 13%). This whole method allows extraction
      and analysis of up to 50 samples per day.

PMID- 11334332
TI  - Internal standard high-performance liquid chromatography method for the
      determination of obidoxime in urine of organophosphate-poisoned patients.
AB  - Obidoxime is an antidote approved for reactivation of inhibited
      acetylcholinesterase in organophosphate poisoning. HPLC methods were described
      for its determination in blood or aqueous solutions but not for the determination
      in urine. Since data for renal obidoxime excretion ranged from 2.2 to 84% of
      administered dose in healthy volunteers depending on the route of administration
      and little is known about pharmacokinetics of obidoxime in severely intoxicated
      patients we developed an internal standard (HI 6) reversed-phase HPLC method for
      determining obidoxime in urine. The mobile phase consisted of methanol, the
      counter ion 1-heptane sulfonic acid and tetrabutylammonium phosphate, the
      stationary phase involved a 5 microm reversed-phase column (125x4 mm). Obidoxime
      was detected spectrophotometrically at 288 nm. The limit of quantification (LOQ)
      was 1 microM, the limit of detection (LOD) 0.5 microM. Linear calibration curves
      were obtained in a concentration range from 1 to 1000 microM. Intra- and inter
      day precision C.V.s were below 4%. Accuracy was 95.9% in the LOQ range. Using
      this method, we were able to quantify obidoxime in urine of an organophosphate
      poisoned patient. Based on this data we calculated that 58% of the administered
      dose was excreted in the urine.

PMID- 11334333
TI  - Application of 2-aminopyridine fluorescence labeling in the analysis of in vivo
      and in vitro metabolism of dextran sulfate sodium by size-exclusion high
      performance liquid chromatography.
AB  - The present study describes a size-exclusion high-performance liquid
      chromatographic method for the separation and quantification of sulfated
      polysaccharides, such as dextran sulfate sodium (DSS). Pyridylamination of DSS
      was achieved without difficulty using 2-aminopyridine as a fluorometric label. In
      addition, 0.1-0.2 M phosphate buffer (pH 3.0) was found to be the mobile phase
      which produced the best separation. In vitro enzymatic degradation of the
      pyridylamino-DSS (PA-DSS5000, Mr 5000) using alpha-amylase and the in vivo
      metabolism in the rat feces after oral administration of PA-DSS5000 were then
      evaluated. Two small peaks of approximately Mr 380 and 600 appeared after co
      incubation with alpha-amylase, indicating PA-DSS5000 may be considerably
      depolymerized. In vivo, however, PA-DSS5000 excreted in the feces was mainly of
      PA-DSS5000 polymer. No peaks of less than Mr 5000 were not clearly detectable in
      the feces because of background fluorescence attributable to gut lumen contents.
      This method of fluorometric analysis allows fairly selective detection of
      sulfated polysaccharides in biological materials.

PMID- 11334334
TI  - Accelerated solvent extraction and liquid chromatography-tandem mass spectrometry
      quantitation of corticosteroid residues in bovine liver.
AB  - A new method for the rapid extraction and unequivocal confirmation of two highly
      potent fluorinated synthetic corticosteroids, dexamethasone and its beta-epimer
      betamethasone, in bovine liver was developed. Flumethasone was used as internal
      standard. An extraction procedure using an accelerated solvent extraction system
      was employed for the isolation of the analytes in liver samples. The procedure
      was highly automated, including defatting and extraction steps, sequentially
      carried out under 1.0 x 10(4) kPa in about 35 min. The extracts were then
      directly analysed by tandem mass spectrometry with on-line liquid chromatography.
      The analytes were ionised in a heated nebulizer interface operating in the
      negative ion mode where the molecular related ions [M-H-CH2O]- were generated for
      each analyte, at m/z 361 for betamethasone and dexamethasone and at m/z 379 for
      flumethasone. They served as precursor ions for collision-induced dissociation
      and three diagnostic product ions for the drugs were identified to carry out
      analyte confirmation by selected reaction monitoring. Assessment of recovery,
      specificity and precision for betamethasone, dexamethasone and flumethasone
      proved the method suitable for confirmatory purposes. The limit of quantification
      of betamethasone and dexamethasone in liver tissue was 1.0 microg/kg.

PMID- 11334335
TI  - Biopartitioning micellar chromatography: an in vitro technique for predicting
      human drug absorption.
AB  - The main oral drug absorption barriers are fluid cell membranes and generally
      drugs are absorbed by a passive diffusion mechanism. Biopartitioning micellar
      chromatography (BMC) is a mode of micellar liquid chromatography that uses
      micellar mobile phases of Brij35 under adequate experimental conditions and can
      be useful to mimic the drug partitioning process in biological systems. In this
      paper the usefulness of BMC for predicting oral drug absorption in humans is
      demonstrated. A hyperbolic model has been obtained using the retention data of a
      heterogeneous set of 74 compounds, which shows predictive ability for drugs
      absorbed by passive diffusion. The model obtained in BMC is compared with those
      obtained using the well-known systems (Caco-2 and TC-7) that use intestinal
      epithelium cell lines. The use of BMC is simple, reproducible and can provide key
      information about the transport properties of new compounds during the drug
      discovery process.

PMID- 11334336
TI  - Identification of quercetin glucuronides in human plasma by high-performance
      liquid chromatography-tandem mass spectrometry.
AB  - After intake of food or herbal medicinal products containing quercetin
      glycosides, the systemic availability of the genuine glycoside, as well as the
      systemic occurrence of the aglycone or conjugates of this polyphenol has been a
      matter of dispute. Consequently, we designed this study to develop a reliable
      method for determination of quercetin and its metabolites. Following consumption
      of fried onions five different glucuronides of quercetin could be identified in
      human plasma samples by means of HPLC-UV-MS/MS. Selective determination of the
      target compounds was achieved by simultaneous UV (254 nm) and MS/MS detection
      with selected reaction monitoring experiments using positive mode electrospray
      ionisation. In contrast, neither the free flavonol nor the genuine glycoside
      could be detected in plasma. Identification of the quercetin glucuronides
      detected in vivo was confirmed by comparison with authentic reference compounds
      synthesised enzymatically using glucuronyl transferase from rabbit liver.

PMID- 11334337
TI  - Purification and characterization of murine beta-nerve growth factor.
AB  - Beta-nerve growth factor (beta-NGF) is a trophic factor in the nervous system. We
      aimed to isolate and characterize this protein in view of its potential
      therapeutic use in neurodegenerative diseases. For purification a two-step ion
      exchange procedure was followed. The characterization was performed using
      separation and immunological techniques, as well as a biological assay. These
      studies showed that the obtained protein consisted of a mixture of beta-NGF
      molecules, intact at their NH2-terminal extreme, and molecules which have lost
      the NH2-terminal octapeptide and exhibit modifications increasing its
      hydrophobicity. All these molecular species were recognized immunologically and
      showed biological activity.

PMID- 11334338
TI  - Determination of formaldehyde in blood plasma by high-performance liquid
      chromatography with fluorescence detection.
AB  - An HPLC method was developed for the determination of formaldehyde in human blood
      plasma. The method was based on the determination of the fluorescent product of
      the chemical reaction between formaldehyde and ampicillin. A 0.2-ml aliquot of
      blood plasma was reacted directly with ampicillin under acidic and heating
      conditions. The reaction product was extracted from the matrix with diethyl ether
      and analyzed by reversed-phase HPLC with fluorescence detection. Recoveries of
      spiked formaldehyde at the low ppm (microg/ml) level were between 93% and 102%
      with relative standard deviations less than 8%. The limits of detection and
      quantitation of formaldehyde in blood plasma samples were 0.46 microg/ml and 0.87
      microg/ml, respectively.

PMID- 11334339
TI  - Headspace solid-phase microextraction profiling of volatile compounds in urine:
      application to metabolic investigations.
AB  - Volatile compounds contribute substantially to the metabolic pool in man. Their
      analysis in body fluids is problematic. We investigated headspace solid-phase
      microextraction (HS-SPME) with Carboxen-polydimethylsiloxane fibres and gas
      chromatography-mass spectrometry for profiling urinary volatile components. These
      fibres were more sensitive for very volatile and sulfur compounds than three
      other phases tested. We detected a wide range of compounds in normal urine at
      acid and alkaline pH. Profiles presented for five individuals with metabolic
      disturbances demonstrate abnormal accumulation of sulfur compounds, fatty acids
      and plasticisers. HS-SPME can complement profiling of non-volatile compounds in
      metabolic investigations and could be a useful extension of the diagnostic
      repertoire.

PMID- 11334340
TI  - Method for reducing endotoxin in Moraxella catarrhalis UspA2 protein
      preparations.
AB  - The UspA2 protein from the bacterium Moraxella catarrhalis is a potential vaccine
      candidate for preventing human diseases caused by this organism. Before a vaccine
      can be administered parentally, the level of endotoxin must be reduced as much as
      possible. However, in this case the endotoxin was very tightly complexed with the
      UspA2 protein and could not be dissociated with Triton X-100. It was found that
      it dissociated from the protein with the zwitterionic detergents Zwittergent 3-12
      and Zwittergent 3-14. The endotoxin could then be separated from the protein by
      either ion-exchange or gel filtration chromatography. Using the limulus
      amoebocyte lysate assay for quantitation, the endotoxin was reduced approximately
      20,000-fold. The removal of residual endotoxin from UspA2 preparations had no
      detrimental effect on the immunological properties of the protein. Mouse antisera
      raised against UspA2 prior to, and following endotoxin reduction exhibited
      comparable antibody and bactericidal titers against the tested strains. Further,
      mice immunized with both preparations, followed by pulmonary challenge with
      either a homologous or a heterologous isolate, exhibited comparable levels of
      clearance.

PMID- 11334341
TI  - Polymer versus monomer as displacer in immobilized metal affinity chromatography.
AB  - Successful immobilized metal affinity chromatography (IMAC) of proteins on Cu2+
      iminodiacetic acid Sepharose has been carried out in a displacement mode using a
      synthetic copolymer of vinyl imidazole and vinyl caprolactam [poly(VI-VCL)] as a
      displacer. Vinyl caprolactam renders the co-polymer with the thermosensitivity,
      e.g., property of the co-polymer to precipitate nearly quantitatively from
      aqueous solution on increase of the temperature to 48 degrees C. A thermostable
      lactate dehydrogenase from the thermophilic bacterium Bacillus stearothermophilus
      modified with a (His)6-tag [(His)6-LDH] has been purified using an IMAC column.
      For the first time it was clearly demonstrated that a polymeric displacer
      [poly(VI-VCL)] was more efficient compared to a monomeric displacer (imidazole)
      of the same chemical nature, probably due to the multipoint interaction of
      imidazole groups within the same macromolecule with one Cu2+ ion. Complete
      elution of bound (His)6-LDH has been achieved at 3.7 mM concentration of
      imidazole units of the co-polymer (5 mg/ml), while this concentration of free
      imidazole was sufficient to elute only weakly bound proteins. Complete elution of
      (His)6-LDH by the free imidazole was achieved only at concentrations as high as
      160 mM. Thus, it was clearly demonstrated, that the efficiency of low-molecular
      mass displacer could be improved significantly by converting it into a polymeric
      displacer having interacting groups of the same chemical nature.

PMID- 11334342
TI  - Determination of biological thiols by high-performance liquid chromatography
      following derivatization by ThioGlo maleimide reagents.
AB  - The importance of thiols has stimulated the development of a number of methods
      for determining glutathione and other biologically significant thiols. Methods
      that are currently available, however have some limitations, such as being time
      consuming and complex. In the present study, a new high-performance liquid
      chromatography (HPLC) method for determining biological thiols was developed by
      using 9-Acetoxy-2-(4-(2,5-dihydro-2,5-dioxo-1H-pyrrol-1-yl)phenyl)-3-oxo-3H
      naphtho[2,1-b]pyran (ThioGlo3) as a derivatizing agent. ThioGlo reacts
      selectively and rapidly with the thiols to yield fluorescent adducts which can be
      detected fluorimetrically (lambda(ex) = 365 nm, lambda(em) = 445 nm). The within
      run coefficient of variation for glutathione (GSH) by this method ranges from
      1.08 to 2.94% whereas the between-run coefficient of variation for GSH is 4.31
      8.61%. For GSH, the detection limit is around 50 fmol and the GSH derivatives
      remain stable for 1 month, if kept at 4 degrees C. Results for GSSG and cysteine
      are also included. The ThioGlo method is compared to our previous method in which
      N-(1-pyrenyl)maleimide (NPM) is used to derivatize thiol-containing compounds.
      The present method offers various advantages over the currently accepted
      techniques, including speed and sensitivity.

PMID- 11334343
TI  - Quantification of BNP7787 (dimesna) and its metabolite mesna in human plasma and
      urine by high-performance liquid chromatography with electrochemical detection.
AB  - A sensitive and accurate assay was developed and validated to determine BNP7787
      (dimesna), a new protector against cisplatin-induced toxicities, and its
      metabolite mesna in plasma and urine of patients. Both analytes were measured as
      mesna in deproteinized plasma or in urine diluted with mobile phase using high
      performance liquid chromatography with an electrochemical detector provided with
      a wall-jet gold electrode. The assays for BNP7787 and mesna in deproteinized
      plasma were linear over the range of 1.6-500 microM and 0.63-320 microM,
      respectively. In plasma, the mean recovery of BNP7787 over the whole
      concentration range was 100.6% and of mesna 94.6%. The lower limits of
      quantitation (LLQs) of BNP7787 and mesna in deproteinized plasma were 1.6 microM
      and 0.63 microM, respectively. For both compounds the within- and between-day
      accuracy and precision of the assay was better than 12%. The assays for BNP7787
      and mesna in urine were linear over the range of 0.8-1200 microM and 0.63-250
      microM, respectively. In urine, the mean recovery of BNP7787 over the whole
      concentration range was 94.1% and of mesna 93.1%. The LLQ of BNP7787 in urine was
      0.8 microM and of mesna 1.6 microM. The within- and between-day accuracy and
      precision of the assay for BNP7787 and mesna was lower than 15%. The stability of
      mesna in urine increased with an increasing concentration of mesna, lower
      temperature and addition of EDTA (1 g/l) and hydrochloric acid (0.2 M). BNP7787
      in urine was stable for at least 24 h at temperatures in the range of -20 degrees
      C up to 37 degrees C and independent of the concentration. The developed assays
      are currently applied for samples of patients with solid tumors participating in
      a phase I trial of BNP7787 in combination with cisplatin.

PMID- 11334344
TI  - High-performance liquid chromatographic assay for acetaminophen glucuronide in
      human liver microsomes.
AB  - A rapid and specific high-performance liquid chromatographic assay was developed
      for the determination of acetaminophen glucuronide formed by human liver
      microsomes. In addition, incubation conditions were systematically evaluated.
      Conditions that yielded the optimal rate of acetaminophen glucuronide formation
      over various concentrations of acetaminophen (0.15-30 mM) consisted of the
      following: 0.1 M potassium phosphate buffer, 1 mM magnesium chloride, 30
      microg/mg alamethicin, 4 mM uridine 5'-diphosphoglucuronic acid at a pH of 7.1.
      Alamethicin produced higher and more consistent APAPG formation rates compared to
      Brij-58. Adding saccharolactone to the incubation medium reduced the velocity of
      the reaction. Acetaminophen glucuronide, acetaminophen, and the internal standard
      (paraxanthine), were analyzed on a C18 column with UV detection at 250 nm. The
      mean correlation coefficient (r2) of the standard curves for acetaminophen
      glucuronide was >0.99 over the range of 0.1-25 nmol. The intra- and inter-day
      coefficients of variation were <4%. This method is suitable for in vitro studies
      using acetaminophen glucuronide formation as an index reaction for UGT activity.

PMID- 11334345
TI  - Simultaneous determination of byak-angelicin and oxypeucedanin hydrate in rat
      plasma by column-switching high-performance liquid chromatography with
      ultraviolet detection.
AB  - A simple and sensitive column-switching HPLC method was developed for the
      simultaneous determination of two furocoumarin compounds, byak-angelicin and
      oxypeucedanin hydrate, which are the main components of hot water extract of
      Angelica dahurica root (AE), in rat plasma. Plasma sample was simply
      deproteinated with perchloric acid. After centrifugation, the supernatant was
      injected into a column-switching HPLC system consisting of a clean-up column
      (Symmetry Shield RP 8, 20x3.9 mm I.D.) and analytical column (Symmetry C18,
      75x4.6 mm I.D.) which were connected with a six-port switching valve. The flow
      rate of the mobile phase (acetonitrile-water, 20:80) was maintained at 1 ml/min.
      Detection was carried out at wavelength 260 nm with a UV detector. The column
      temperature was maintained at 40 degrees C. The calibration curves of byak
      angelicin and oxypeucedanin hydrate were linear over the ranges 19.6 to 980 ng/ml
      (r2>0.997). The accuracy of these analytes was less than 4.4%. The intra- and
      inter-day relative standard deviations of byak-angelicin and oxypeucedanin
      hydrate were within 12.0% and 12.7%, respectively. The present method was applied
      for the analysis of plasma concentration from rats after administration of AE.

PMID- 11334346
TI  - Rapid and simultaneous determination of mycophenolic acid and its glucuronide
      conjugate in human plasma by ion-pair reversed-phase high-performance liquid
      chromatography using isocratic elution.
AB  - A high-performance liquid chromatographic method has been developed for the
      simultaneous determination of mycophenolic acid (MPA) and its glucuronide
      conjugate (MPAG) in human plasma. The method involves protein precipitation with
      acetonitrile, followed by ion-pair reversed-phase chromatography on C18 column,
      with a 40 mM tetrabutyl ammonium bromide (TBA)-acetonitrile (65:35, v/v) mobile
      phase. A 20-microl volume of clear supernatant was injected after centrifugation,
      and the eluent was monitored at 304 nm. No interference was found either with
      endogenous substances or with many concurrently used drugs, indicating a good
      selectivity for the procedure. Calibration curves were linear over a
      concentration range of 0.5-20.0 microg/ml for MPA and 5-200 microg/ml for MPAG.
      The accuracy of the method is good, that is, the relative error is below 5%. The
      intra- and inter-day reproducibility of the analytical method is adequate with
      relative statistical deviations of 6% or below. The limits of quantification for
      MPA and MPAG were lower than 0.5 and 5.0 microg/ml, respectively, using 50 microl
      of plasma. The method was used to determine the pharmacokinetic parameters of MPA
      and MPAG following oral administration in a patient with renal transplantation.

PMID- 11334347
TI  - High-throughput cytochrome P450 (CYP) inhibition screening via cassette probe
      dosing strategy. II. Validation of a direct injection/on-line guard cartridge
      extraction-tandem mass spectrometry method for CYP2D6 inhibition assessment.
AB  - A highly efficient direct injection/on-line guard cartridge extraction-tandem
      mass spectrometry (DI/GCE-MS-MS) method has been validated for high-throughput
      evaluation of cytochrome P450 (CYP) 2D6 inhibition potential using human hepatic
      microsomes and 96-well microtiter plates. Microsomal incubations were terminated
      with formic acid, centrifuged, and the resulting supernatants were injected for
      DI/GCE-MS-MS analysis. Due to the novel use of an extremely short C18 guard
      cartridge, this method exhibits several advantages, such as no sample
      preparation, excellent on-line extraction, short run time (2.5 min), and
      minimized source contamination and performance deterioration. The DI/GCE-MS-MS
      method demonstrates acceptable accuracy and precision for the quantification of
      dextrorphan, a marker metabolite of dextromethorphan mediated by CYP2D6, in
      microsomal incubations. The CYP2D6 inhibition assay has been validated using
      quinidine as a known selective inhibitor of the isoform. The IC50 value (0.20
      microM) measured by the new method is in good agreement with the literature value
      (0.22 microM).

PMID- 11334348
TI  - From receptor recognition mechanisms to bioinspired mimetic antagonists in HIV
      1/cell docking.
AB  - Understanding the ways in which two or more proteins interact may give insight
      into underlying binding and activation mechanisms in biology, methods for protein
      separation and structure-based antagonism. This review describes ways in which
      protein recognition has been explored in our laboratory for the HIV-1/cell entry
      process. Initial contact between an HIV-1 virion particle and a human cell occurs
      between gp120 (an HIV-1 envelope protein) and CD4 (a human extracellular
      signaling protein). This interaction leads to a sequence of events which includes
      a conformational change in gp120, fusion of the HIV-1 and cellular membranes and
      eventual infection of the cell. Using an optical biosensor and a reporter
      antibody, we have been able to measure the conformational change in gp120 that
      occurs upon CD4 binding. We also have used this biosensor system to characterize
      CD4 mimetics, obtained by peptide synthesis in miniprotein scaffolds. Phage
      display techniques have been employed to identify novel miniprotein sequences.
      The combination of biosensor interaction kinetics analysis and phage display
      provides a useful approach for understanding the recognition mechanisms involved
      in the HIV/cell docking process. This approach may also be useful in
      investigating other protein complexes of importance in health and disease.

PMID- 11334349
TI  - Determination of opipramol in human plasma by high-performance liquid
      chromatography with photometric detection using a cyanopropyl column.
AB  - A high-performance liquid chromatographic method is described for the
      determination of opipramol in human plasma. Opipramol was extracted into tert.
      butylmethyl ether, separated on a cyanopropyl silica column and detected at 254
      nm. Imipramine was used as internal standard. The limit of quantitation was 250
      pg/ml using 1.5 ml plasma. Precision was better than 9%, inaccuracy less than 8%.
      The assay is more sensitive than previously published methods, and it has been
      applied to the analysis of plasma samples from a pharmacokinetic study.

PMID- 11334351
TI  - Determination of lysophosphatidic acids by capillary electrophoresis with
      indirect ultraviolet detection.
AB  - Lysophosphatidic acid (LPA) is the simplest form of lysophospholipid. Molecular
      species of LPA have been identified as the potent components in the ovarian
      cancer activation factor. The elevated plasma LPAs may be used as potential
      biomarkers for the early detection of ovarian cancer. This paper is the first
      report on the quantitative analysis of molecular species of LPA using capillary
      electrophoresis. In this work, the separation of LPAs was achieved within 14 min
      in an adenosine monophosphate-borate-methanol-water solution, and the measurement
      was accomplished by indirect UV detection. With LPA (D) as internal standard, the
      method had linear calibration ranges for LPAs from 2.8 to 75 microM. The
      detection limits for various molecular species of LPA were from 1.2 to 2.3 microM
      by the pressure injection at 3.45 kPa for 5 s. The method had been applied to
      serum fortified with LPA (S), LPA (O), LPA (P), and LPA (M) and the recoveries
      ranged from 83 to 112%.

PMID- 11334350
TI  - High-performance liquid chromatographic-tandem mass spectrometric method for the
      determination of ethionamide in human plasma, bronchoalveolar lavage fluid and
      alveolar cells.
AB  - We have developed and validated an accurate, sensitive, and rapid high
      performance liquid chromatographic-tandem mass spectrometric method (HPLC-MS-MS)
      for the determination of ethionamide in plasma, bronchoalveolar fluid (BAL) and
      alveolar cells (AC). The retention times for ethionamide, clemastine fumarate
      (internal standard for plasma), promethazine (internal standard for plasma) and
      propranolol (internal standard for BAL and AC) were approximately 2.62, 1.21,
      2.14, and 2.22 min, respectively, with a total run time of 3.2 min. Ethionamide
      detection for plasma was carried out on a PE Sciex API III (Perkin-Elmer, Foster
      City, CA, USA). BAL and cell pellets and some plasma specimens were analyzed on a
      Micromass Quattro LC (Micromass Co., Manchester, UK). The detection limits for
      ethionamide were 0.05 microg/ml for plasma, and 0.005 microg/ml for BAL
      supernatants and alveolar cell suspensions.

PMID- 11334352
TI  - On-line extraction using an alkyl-diol silica precolumn for racemic citalopram
      and its metabolites in plasma. Results compared with solid-phase extraction
      methodology.
AB  - Sample preparation is usually the most critical and time consuming step when
      using HPLC for drug analysis in biological matrixes. Sample extracts have to be
      clean considering both chromatographic interferences and column maintenance. To
      meet some of these criteria a fully automated on-line extraction (OLE) analysis
      method was developed for the antidepressant drug citalopram and its two
      demethylated metabolites, using an RP-C4-ADS extraction column. A comparison
      between the new OLE method and an off-line solid-phase extraction method showed
      that the two methodologies were equal in analytical precision but that the OLE
      method was faster and therefore superior in sample capacity per day.

PMID- 11334353
TI  - Determination of inhibitors' potency (IC50) by a direct high-performance liquid
      chromatographic method on an immobilised acetylcholinesterase column.
AB  - An immobilised acetylcholinesterase (AChE) stationary phase was prepared by using
      an in situ AChE immobilisation procedure. A stainless steel column packed with
      epoxide silica was connected to the HPLC system and the enzyme solution at pH 5.8
      was recycled through the column at a flow-rate of 0.5 ml/min for 24 h. The
      activity of the immobilised AChE was determined by injecting the substrate
      acetylthiocholine, using as mobile phase 0.1 M phosphate buffer (pH 7.4)
      containing Ellman's reagent [5,5'-dithio-bis(2-nitrobenzoic acid)] and measuring
      the area of the obtained peak with UV detection at 412 nm. The effect of AChE
      inhibitors tacrine, edrophonium and donepezil were evaluated by the simultaneous
      injection of each inhibitor with the substrate. The resulting decrease in the
      AChE activity, as expressed by the decrease of the peak area detected at 412 nm,
      was related to the concentration and potency of the solutes. The obtained IC50
      values were compared with those derived by the conventional spectrophotometric
      method. This immobilized enzyme reactor, included in a chromatographic system,
      can be used for the rapid screening for new inhibitors allowing for the on-line
      determination of a compound's inhibitory potency. The advantages over the
      conventional methods are the increased enzyme stability and system automation
      which allows a large number of compounds to be analysed continuously.

PMID- 11334354
TI  - Simultaneous high-performance liquid chromatographic determination of urinary
      mandelic and phenylglyoxylic acids as indirect evaluation of styrene exposure.
AB  - Styrene is rapidly metabolised to mandelic acid (MA) and phenylglyoxylic acid
      (PGA), which are excreted in urine. In this work, we have developed a simple,
      sensitive and specific high-performance liquid chromatographic method with minor
      sample preparation procedures for the simultaneous determination of MA and PGA in
      urine of workers exposed to styrene. Moreover, urine samples from workers of two
      plastic factories were analysed, styrene exposure levels of the workers were
      estimated and data obtained from the two factories were compared.

PMID- 11334355
TI  - Liquid chromatographic determination of ketoconazole, a potent inhibitor of
      CYP3A4-mediated metabolism.
AB  - A high-performance liquid chromatographic assay with UV detection has been
      developed for the determination of ketoconazole in human plasma. Quantitative
      extraction was achieved by a single solvent extraction involving a mixture of
      acetonitrile-n-butyl chloride (1:4, v/v). Ketoconazole and the internal standard
      (clotrimazole) were separated on a column packed with Inertsil ODS-80A material
      and a mobile phase composed of water-acetonitrile-tetrahydrofuran-ammonium
      hydroxide-triethylamine (45:50.2:2.5:0.1:0.1, v/v). The column effluent was
      monitored at a wavelength of 206 nm with a detector range set at 0.5. The
      calibration graph was linear in the range of 20-2000 ng/ml, with a lower limit of
      quantitation of 20.0 ng/ml. The extraction recoveries for ketoconazole and
      clotrimazole in human plasma were 93+/-9.7% and 83+/-10.0%, respectively. The
      developed method has been successfully applied to a clinical study to examine the
      pharmacokinetics of ketoconazole in a cancer patient.

PMID- 11334356
TI  - Liquid chromatographic-mass spectrometric determination of celecoxib in plasma
      using single-ion monitoring and its use in clinical pharmacokinetics.
AB  - Celecoxib is a cyclooxygenase-2 specific inhibitor, that has been recently and
      intensively prescribed as an anti-inflammatory drug in rheumatic osteoarthritis.
      A robust, highly reliable and reproducible liquid chromatographic-mass
      spectrometric assay is developed for the determination of celecoxib in human
      plasma using sulindac as an internal standard. The run cycle-time is <4 min. The
      assay method involved extraction of the analytes from plasma samples at pH 5 with
      ethyl acetate and evaporation of the organic layer. The reconstituted solution of
      the residue was injected onto a Shim Pack GLC-CN, C18 column and chromatographed
      with a mobile phase comprised of acetonitrile-1% acetic acid solution (4:1) at a
      flow-rate of 1 ml/min. The mass spectrometer (LCQ Finnigan Mat) was programmed in
      the positive single-ion monitoring mode to permit the detection and quantitation
      of the molecular ions of celecoxib and sulindac at m/z 382 and 357, respectively.
      The peak area ratio of celecoxib/sulindac and concentration are linear (r2>0.994)
      over the concentration range 50-1000 ng/ml with a lowest detection limit of 20
      ng/ml of celecoxib. Within- and between-day precision are within 1.58-4.0%
      relative standard deviation and the accuracy is 99.4-107.3% deviation of the
      nominal concentrations. The relative recoveries of celecoxib from human plasma
      ranged from 102.4 to 103.3% indicating the suitability of the method for the
      extraction of celecoxib and I.S. from plasma samples. The validated LC-MS method
      has been utilized to establish various pharmacokinetic parameters of celecoxib
      following a single oral dose administration of celecoxib capsules in two selected
      volunteers.

PMID- 11334357
TI  - Application of microcolumn ion chromatography using anion exchangers modified
      with dextran sulfate for the determination of alkali and alkaline-earth metal
      ions.
AB  - Microcolumn ion chromatography using anion exchangers modified with dextran
      sulfate has been applied to the determination of alkali and alkaline-earth metal
      ions contained in guinea pig serum and bovine serum. These serums contained Na+,
      NH4+, K+, Mg2+ and Ca2+ and they were indirectly detected at 200 nm. The
      determination was done without any pretreatment procedure other than dilution.

PMID- 11334358
TI  - Oxalic acid stabilizes dopamine, serotonin, and their metabolites in automated
      liquid chromatography with electrochemical detection.
AB  - Use of antioxidative agents is required in automated LC assay of microdialysis
      samples, due to rapid degradation of the monoamine neurotransmitters and their
      metabolites. Addition of oxalic acid prevented degradation of dopamine,
      serotonin, 3,4-dihydroxyphenylacetic acid, homovanillic acid and 5
      hydroxyindoleacetic acid efficiently: after a 24-h incubation at room temperature
      the decreases in peak heights were less than 10%. The long-term stability of the
      analytes, however, was still enhanced when acetic acid and L-cysteine were
      included in the solution. Using this antioxidative solution, the monoamine
      neurotransmitters and their metabolites could be determined with an automated LC
      assay even at room temperature.

PMID- 11334359
TI  - Small blood volumes from children for quantitative sotalol determination using
      high-performance liquid chromatography.
AB  - A sensitive high-performance liquid chromatographic method using fluorescence
      detection has been developed for sotalol determination in small plasma samples of
      children and newborns with limited blood volume. In sample sizes of 100 microl of
      plasma, sotalol was extracted using an internal standard and solid-phase
      extraction columns. Chromatographic separation was performed on a Spherisorb C6
      column of 150x4.6 mm I.D. and 5 microm particle size at ambient temperature. The
      mobile phase consisted of acetonitrile-15 mM potassium phosphate buffer (pH 3.0)
      (70:30, v/v). The excitation wavelength was set at 235 nm, emission at 300 nm.
      The flow-rate was 1 ml/min. Sotalol and the internal standard atenolol showed
      recoveries of 107+/-8.9 and 97+/-8.1%, respectively. The linearity range for
      sotalol was between 0.07 and 5.75 microg/ml, the limit of quantitation 0.09
      microg/ml. Precision values expressed as percent relative standard deviation of
      intra-assay varied between 0.6 and 13.6%, that of inter-assay between 2.4 and
      14.4%. Accuracy varied between 86.1 and 109.8% (intra-assay) and 95.4 and 103.3%
      (inter-assay). Other clinically used antiarrhythmic drugs did not interfere. As
      an application of the assay, sotalol plasma concentrations in a 6-year-old child
      with supraventricular tachycardia treated with oral sotalol (3.2 mg/kg per day)
      are reported.

PMID- 11334360
TI  - Plasma L-arginine is markedly reduced in pregnant women affected by preeclampsia.
AB  - The objective of this study was to determine the concentration of free L-amino
      acids and in particular of L-arginine in the plasma of pregnant women affected by
      preeclampsia compared to healthy pregnant women in order to know if an alteration
      in the concentrations of these amino acids occurs in preeclamspia. Twelve
      pregnant women affected by preeclampsia and twelve pregnant control women, ages
      28-35 years old and at the 35-36 weeks of pregnancy were studied. The blood
      analysis of free amino acids was carried out by using a high performance liquid
      chromatographic (HPLC) fluorometric method and OPA-NAC as derivatizing agent for
      the amino acid determination. In the blood of women affected by preeclampsia L
      arginine is markedly reduced compared to controls (about five-fold lower,
      P<0.01). The other amino acids also are significantly reduced, but to lesser
      extents (about 1.5 times lower, P<0.05). Thus, the determination of L-arginine in
      the blood of pregnant women could potentially constitute an additional marker for
      the early diagnosis of preeclampsia.

PMID- 11334361
TI  - Unique organoprotective properties of a novel IH636 grape seed proanthocyanidin
      extract on cadmium chloride-induced nephrotoxicity, dimethylnitrosamine (DMN)
      induced splenotoxicity and mocap-induced neurotoxicity in mice.
AB  - Several observations, both in humans and laboratory animals, have suggested that
      proanthocyanidins exhibit a broad spectrum of pharmacological, therapeutic and
      chemoprotective properties. Specifically, some of our earlier studies have shown
      that IH636 grape seed proanthocyanidin extract (GSPE, commercially known as
      ActiVin) provides excellent concentration- and dose-dependent protection against
      toxicities induced by diverse agents, such as acetaminophen, hydrogen peroxide,
      12-O-tetradecanoylphorbol-13-acetate (TPA), smokeless-tobacco extract, idarubicin
      and 4-hydroxyperoxycyclophosphamide in both in vitro and in vivo models. In some
      models, GSPE proved to be a better cytoprotectant than vitamins C, E and beta
      carotene. The purpose of this investigation was three fold: (i) to indirectly
      assess the bioavailability of GSPE in multiple target organs, (ii) quantify
      GSPE's capacity to avert cadmium chloride (CdCl2)-induced nephrotoxicity,
      dimethylnitrosamine (DMN)-induced splenotoxicity and O-ethyl-S,S-dipropyl
      phosphorodithioate (MOCAP)-induced neurotoxicity, and lastly (iii) to evaluate
      possible mechanisms of protection in mice. In order to determine all these, three
      separate experiments were designed and each experiment consisted of four groups,
      such as vehicle control, GSPE alone, toxicant alone and GSPE + toxicant. GSPE was
      administered orally (100 mg/Kg) for 7-8 days prior to the toxicant exposure.
      Parameters of the analyses included evaluation of serum chemistry changes (ALT,
      BUN and CK), histopathology and integrity of genomic DNA, both quantitatively and
      qualitatively. Results indicate that GSPE preexposure prior to cadmium chloride
      and DMN provided near complete protection in terms of serum chemistry changes
      (ALT, BUN and CK) and inhibition of both forms of cell death. e.g., apoptosis and
      necrosis. DNA damage, a common denominator usually associated with both apoptosis
      and necrosis was significantly reduced by GSPE treatment. Histopathological
      examination of organs correlated strongly with the changes in serum chemistry and
      the DNA modification data. Surprisingly, MOCAP exposure showed symptoms of
      neurotoxicity coupled with serum chemistry changes in the absence of any
      significant genomic DNA damage or brain pathology. Although, GSPE appeared to
      partially protect the neural tissue, it powerfully antagonized MOCAP-induced
      mortality. Taken together, this study suggests that in vivo GSPE-preexposure may
      protect multiple target organs from a variety of toxic assaults induced by
      diverse chemical entities.

PMID- 11334362
TI  - Increased polyploid incidence is associated with abnormal copper accumulation in
      the liver of LEC mutant rat.
AB  - Long-Evans Cinnamon (LEC) rats are deleted at the p-type copper transport ATPase
      gene (Atp7b), so that they exhibit abnormal hepatic copper concentration. In this
      study, it was confirmed that LEC rat liver possesses a feature of increase in
      polyploid. Furthermore, a segregation analysis using backcrosses between LEC and
      F344 normal rats showed that the increased polyploid incidence is strongly
      associated with excessive copper content in their liver. These results should
      demonstrate that copper cytotoxicity leads to the impairment of mitotic
      progression, resulting in the increase of polyploid in the liver of LEC rats.

PMID- 11334363
TI  - Trauma patients with positive cultures have higher levels of circulating
      macrophage migration inhibitory factor (MIF).
AB  - Macrophage migration inhibitory factor (MIF) is a pituitary "stress" hormone that
      plays a critical role in the host immune response. The aims of the study were to
      determine whether MIF was detectable in the circulation of trauma patients, to
      assess whether MIF levels were associated with injury severity, days post injury,
      infection, and to examine concentrations of other pro-inflammatory cytokines in
      circulation. We collected plasma samples from 35 trauma (multiple injury)
      patients and 18 healthy controls. Concentrations of MIF, TNF-alpha, IL-1beta, and
      IL-6 were measured by ELISA. Average MIF concentration in plasma of trauma
      patients was 14 fold higher than that of healthy controls (19,439+/-2,615 pg/ml
      in trauma vs 1,337+/-286 pg/ml in control; p=0.0002). There was no correlation
      between MIF values and injury severity score or days post injury. Average level
      of IL-6 in trauma patients was 587+/-85 pg/ml but was not correlated with MIF
      concentration. TNF-alpha and IL-1beta were not detectable in trauma patients or
      healthy controls. Higher MIF levels were associated with positive cultures
      (blood, urine, sputum, wound). These data suggest that MIF may be a possible
      indicator of infection in trauma patients.

PMID- 11334364
TI  - In vivo protection of dna damage associated apoptotic and necrotic cell deaths
      during acetaminophen-induced nephrotoxicity, amiodarone-induced lung toxicity and
      doxorubicin-induced cardiotoxicity by a novel IH636 grape seed proanthocyanidin
      extract.
AB  - Grape seed extract, primarily a mixture of proanthocyanidins, has been shown to
      modulate a wide-range of biological, pharmacological and toxicological effects
      which are mainly cytoprotective. This study assessed the ability of IH636 grape
      seed proanthocyanidin extract (GSPE) to prevent acetaminophen (AAP)-induced
      nephrotoxicity, amiodarone (AMI)-induced lung toxicity, and doxorubicin (DOX)
      induced cardiotoxicity in mice. Experimental design consisted of four groups:
      control (vehicle alone), GSPE alone, drug alone and GSPE+drug. For the
      cytoprotection study, animals were orally gavaged 100 mg/Kg GSPE for 7-10 days
      followed by i.p. injections of organ specific three drugs (AAP: 500 mg/Kg for 24
      h; AMI: 50 mg/Kg/day for four days; DOX: 20 mg/Kg for 48 h). Parameters of study
      included analysis of serum chemistry (ALT, BUN and CPK), and orderly
      fragmentation of genomic DNA (both endonuclease-dependent and independent) in
      addition to microscopic evaluation of damage and/or protection in corresponding
      PAS stained tissues. Results indicate that GSPE preexposure prior to AAP, AMI and
      DOX, provided near complete protection in terms of serum chemistry changes (ALT,
      BUN and CPK), and significantly reduced DNA fragmentation. Histopathological
      examination of kidney, heart and lung sections revealed moderate to massive
      tissue damage with a variety of morphological aberrations by all the three drugs
      in the absence of GSPE preexposure than in its presence. GSPE+drug exposed
      tissues exhibited minor residual damage or near total recovery. Additionally,
      histopathological alterations mirrored both serum chemistry changes and the
      pattern of DNA fragmentation. Interestingly, all the drugs, such as, AAP, AMI and
      DOX induced apoptotic death in addition to necrosis in the respective organs
      which was very effectively blocked by GSPE. Since AAP, AMI and DOX undergo
      biotransformation and are known to produce damaging radicals in vivo, the
      protection by GSPE may be linked to both inhibition of metabolism and/or
      detoxification of cytotoxic radicals. In addition, its' presumed contribution to
      DNA repair may be another important attribute, which played a role in the
      chemoprevention process. Additionally, this may have been the first report on AMI
      induced apoptotic death in the lung tissue. Taken together, these events
      undoubtedly establish GSPE's abundant bioavailability, and the power to defend
      multiple target organs from toxic assaults induced by structurally diverse and
      functionally different entities in vivo.

PMID- 11334365
TI  - Binding of alkyl- and alkoxy-substituted simple phenolic compounds to human serum
      proteins.
AB  - Wood creosote, primarily a mixture of simple alkyl- and/or alkoxy-substituted
      phenolic compounds with closely related structures, has long been used as an oral
      antidiarrheal agent. The use of wood creosote as a parenteral antidiarrheal agent
      was investigated, and for basic pharmacokinetic data we measured the extent of
      equilibrium binding of its six major constituent phenolic compounds to human
      serum proteins using an ultrafiltration method. The percent binding of these
      major constituent phenolic compounds, namely phenol, guaiacol, p-cresol, o
      cresol, creosol and 4-ethylguaiacol, bound to 40-mg/ml human serum albumin was
      15.5+/-0.9, 28.0+/-1.5, 37.2+/-0.7, 52.3+/-5.3, 36.8+/-2.0 and 56.7+/-2.4%,
      respectively, while percent binding to human serum (68 mg protein/ml) was 41.3+/
      0.7, 42.6+/-0.5, 64.8+/-0.4, 70.1+/-1.6, 65.7+/-0.2 and 83.1+/-0.1% (mean +/-
      standard deviation, n = 4), respectively, when tested individually at a
      concentration of 500 micromol/l. Saturation of binding was not observed for the
      phenolic compounds up to a concentration of 50 mmol/l. Phenolic compounds with a
      lipophilic substituent showed higher percent binding to proteins than those
      without it. We conclude that simple phenolic compounds having alkyl- and/or
      alkoxy-substituents bind to serum proteins to a considerable extent and that the
      binding is hydrophobic and nonspecific.

PMID- 11334366
TI  - Detection of restricted specificity of endonucleases by non-poisson analysis of
      their enzymatic digestion products.
AB  - Endonucleases, enzymes of the hydrolase class that cleave DNA or RNA within the
      substrate molecule, play numerous critical roles in molecular biologic,
      pharmacologic, and pathologic events as well as constitute invaluable tools used
      in genetic analysis, gene cloning and DNA sequencing. These enzymes have two
      critical parameters, activity and site specificity. The former is easily measured
      in commonly used assays, but the latter must be analyzed by more complex,
      indirect assays that are often not even carried out. We now show how both
      parameters can be measured directly and simultaneously in the same assay, which
      is not significantly more labor intensive than the commonly used activity assay.
      The effectiveness and accuracy of this assay was tested on a series of five
      bacterial restriction enzymes which recognized, respectively, 1, 2, 3, 4, and a
      large number (26) of reactive sites on a small, uniform DNA substrate molecule.
      We found that the distributions of the reaction products of all five enzymes
      precisely followed that predicted by the Binominal and Poisson distributions for
      the number of sites recognized by each enzyme, and that these distributions could
      be used to determine this number experimentally. In this way a measure of site
      specificity can be made for each enzyme as well as its activity. This new assay
      should be used routinely in a number of laboratories that now employ conventional
      assays for endonuclease activity.

PMID- 11334367
TI  - Telomerase activity in patients with chronic myeloid leukemia and lymphoma.
AB  - Telomeres are repeated DNA sequences, positioned at the ends of chromosomes and
      are essential for the stable maintenance of chromosomes. The telomere length
      serves as a mitotic clock determining the remaining replicative capacity of the
      cell. Telomeric sequences are lost during each cell division, leading to a
      process thought to contribute to senescence and cell death. The enzyme telomerase
      adds 5'-TTAGGG-3' repeats to the mammalian telomeres and maintains the telomere
      length. Telomerase is normally inactive in most somatic cells but telomerase
      activity is observed in malignancies. In this study telomerase activity was
      analyzed in patients with chronic myeloid leukemia (CML) and lymphoma by PCR and
      ELISA. This approach combines highly specific amplification of the telomerase
      mediated elongation products with nonradioactive detection in a highly sensitive
      photometric ELISA. The PCR products were also analyzed by Southern blotting. The
      telomerase-specific PCR products were seperated by electrophoresis and
      transferred to a nylon membrane with subsequent detection of the biotinylated
      amplificates. High activity levels were detected in 17 CML ( 34%) patients. On
      the other hand, no activity was observed in lymphoma patients. An increase in the
      shorter telomeric bands was observed in CML patients who displayed a high level
      of telomerase activity. In contrast to the low enzyme activity, evidence of
      telomeric repeats were also found in some lymphoma patients by Southern blotting.
      This may indicate that lymphoma cells may make use of different pathways for
      maintaining the length of their telomeres.

PMID- 11334368
TI  - Findings on nuclear staining using hoechst dye in cleaved unfertilized eggs
      obtained by repeated superovulation with gonadotrophin.
AB  - Unfertilized eggs showing abnormal cleavage are ovulated with repeated induction
      of super-ovulation. In this study, the presence or absence of the nucleus was
      examined in segmented blastomeres of these unfertilized eggs using Hoechst dye.
      Unfertilized eggs showing a morula stage-like cleavage obtained by repeated
      superovulation 4 times using PMSG/hCG were collected from mice oviducts. The
      collected eggs were nuclear-stained using Hoechst dye and examined by
      fluorescence microscope. No positive staining of the nucleus was observed in any
      of the blastomeres, and only diffuse fluorescence was noted in the cytoplasm.
      Therefore, we concluded that no nucleus was present in these blastomeres and that
      cleavage was a degenerative change.

PMID- 11334369
TI  - Quantitative determination of urinary 8-hydroxydeoxyguanosine (8-OH-dg) by using
      ELISA.
AB  - In order to establish a quantitative assay for 8-OHdG concentrations in urine, we
      examined the precision of a test for the recovery of 8-OHdG in urine by using an
      ELISA method. The coefficient of variation (CV) for assay with incubation in
      water or air ranged between 7.0% and 8.4% and between 19.2% and 30.6%,
      respectively. The data by using incubation in water gave higher accuracy than
      those in air. The recovery rates of 8-OHdG in urine sample ranged from 95 - 114%.
      Our results indicated that the excellent sensitivity of this ELISA kit by using
      incubation in water makes its use possible for the determination in urine with a
      good reproducibility and recovery of 8-OHdG-spiked samples.

PMID- 11334370
TI  - Cerebral artery selective inhibition of protein kinase c-mediated contraction by
      hns-32, a novel azulene-1-carboxamidine derivative.
AB  - The vasorelaxant actions of a novel azulene-1-carboxamidine derivative, HNS-32,
      were investigated on the tension development evoked by phorbol 12, 13 dibutyrate
      (PDBu) in cerebral and femoral arteries isolated from the dogs. In basilar
      artery, HNS-32 inhibited almost completely PDBu-induced contraction in a
      concentration-dependent manner with potency about 10 times stronger than that of
      fasudil, a protein kinase inhibitor. In contrast, in femoral artery, HNS-32
      failed to suppress the tension development in response to PDBu whereas fasudil
      inhibited it with a similar potency as in basilar artery. These findings indicate
      that HNS-32 selectively suppresses cerebral artery contraction mediated via an
      activation of protein kinase C.

PMID- 11334371
TI  - Serum leptin correlates with serum uric acid but not serum testosterone in non
      obese male adolescents.
AB  - To identify the serum factors that affect circulating leptin levels, we measured
      the serum concentrations of leptin, testosterone (T), estradiol (E), serum
      alanine aminotransferase, total cholesterol and uric acid (UA) in healthy male
      adolescents (age, 18.3 +/- 0.1 years, n=96). We also measured body mass index
      (BMI), percent body fat and thickness of skin fold to assess the effect of body
      constitution on serum leptin level. Since serum concentration of leptin
      significantly correlated with BMI (r=0.820, p<0.001), we analyzed the relation
      ship between leptin/BMI ratio (L/BMI) and serum parameters. Analysis of data of
      subjects with normal serum T level showed a significant inverse correlation
      between L/BMI and serum T levels (n=96, r=-0.294, p<0.005), but no such
      correlation was present among non-obese subjects (n=70) with BMI of +/-20% of
      normal (22 kg/m2). There was no correlation between L/BMI and serum E level.
      Serum UA level significantly correlated with L/BMI in both the test group (n=96,
      r=0.520, p<0.001) and non-obese subjects (r=0.369, p<0.005). Stepwise multiple
      regression analysis showed that UA independently and significantly influenced
      serum leptin levels in both the test and control groups. Our results demonstrate
      that T weakly influences serum leptin concentration, and that UA concentrations
      strongly influences serum leptin in healthy male adolescents independent of their
      obesity level.

PMID- 11334372
TI  - Rates of gluconeogenesis in perfused liver of alloxan-diabetic fed rats.
AB  - The maximal capacity of the liver to produce glucose was examined using a
      technique, which permited to investigate gluconeogenesis in diabetic fed rats.
      Diabetes was obtained with an iv injection of alloxan (40 mg/kg). Livers from
      diabetic fed rats were perfused in situ and gluconeogenesis from different
      glucose precursors were measured one week after alloxan injection. Hepatic
      gluconeogenesis from L-alanine (5 mM) was absent. However, increased urea,
      pyruvate and L-lactate production was observed during L-alanine infusion.
      Differently of L-alanine, alloxan-diabetic fed rats showed increased hepatic
      glucose production from pyruvate (5 mM), L-lactate (2 mM) and D-frutose (5 mM).
      Additionally, increased L-lactate production from pyruvate and pyruvate
      production from L-lactate were observed. However, pyruvate production from L
      lactate was lower in the diabetic group when compared with control group.
      Moreover similar tendency were observed for L-alanine and D-frutose. Taken
      together our results demonstrate influence of the cytosolic redox potential
      (NADH/NAD+ ratio) in the metabolic fate L-alanine. Additionally, in contrast to L
      alanine, diabetic rats not only showed increased rate of glucose production from
      L-glutamine (5 mM) but also higher values than control rats.

PMID- 11334373
TI  - Dissociation of epistatic effects involved in fasting and postprandial
      hyperglycemia.
AB  - The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is an animal model for obese
      type non-insulin-dependent diabetes mellitus (NIDDM) in humans. Our previous
      study has identified four epistatic interactions between Niddel (chromosome 7)
      and 2/of (chromosome 14), Niddel and 3/of (chromosome 15), Nidde2 and 4/of
      (chromosome 15), and Nidde2 and 5/of (chromosome 17), which exerted effects on
      NIDDM, by performing least squares analysis of variance of all pairs of
      informative markers in 160 F2 progenies bred from the OLETF rat. In the present
      study, we found that the four interactions affect postprandial glucose
      metabolism, but not glucose levels during fasting states. In addition, we
      identified novel interactions between Nidde6 (chromosome 1) and 7/of (chromosome
      13), and Nidde8 (chromosome 5) and 9/of (chromosome 19), which is involved in
      fasting glucose levels but not postprandial glucose levels. These findings
      demonstrate that distinction between genetic bases of fasting hyperglycemia and
      postprandial hyperglycemia is made by not only single main effect but also
      epistatic interaction effect of NIDDM loci.

PMID- 11334374
TI  - Angiotensin II activates a bumetanide sensitive increase in 86RB+ efflux in the
      rat heart.
AB  - We previously reported that alpha-adrenoceptor (AR) stimulation of the isolated
      perfused rat heart increased the efflux of 42K+ and the K+ analogue 86Rb+. The
      main part of this increase was bumetanide sensitive, indicating an activation of
      the Na+/K+/2Cl- cotransporter. The purpose of the present study was to
      investigate the effects of angiotensin II (1-100 nmol/l) and the protein kinase C
      (PKC) activator PMA (phorbol-12-myristate-13-acetate, 1-1000 nmol/l) on 86Rb+
      efflux from isolated rat hearts and to compare the effects with the effect of the
      alpha1- AR agonist phenylephrine (30 micromol/l) in the presence of a beta-AR
      antagonist. Phenylephrine increased the 86Rb+ efflux rate by 47+/-4.1% (n=5,
      p<0.001). Angiotensin II induced a maximal increase in 86Rb+ efflux rate of 13+/
      1.6% (n=12, p<0.0001). The effect of angiotensin II was totally eliminated by
      bumetanide (50 micromol/l). PMA decreased the 86Rb+ efflux rate by 23+/-7.0 %
      (n=7, p=0.02) and this effect of PMA was not sensitive to bumetanide. Pre
      treatment of the hearts with PMA for 30 min did not influence the response to
      phenylephrine. In conclusion, angiotensin II stimulation, but not PKC activation
      by PMA increased the 86Rb+ efflux rate in isolated rat hearts, but the effect was
      smaller than that of alpha1- AR stimulation. The effect of angiotensin II was
      completely abolished by bumetanide indicating an activation of the Na+/K+/2Cl- 
      cotransporter.

PMID- 11334375
TI  - Embodiment: an introduction.

PMID- 11334376
TI  - The 'medical body' as philosophy's arena.
AB  - Medicine, as Byron Good argues, reconstitutes the human body of our daily
      experience as a "medical body," unfamiliar outside medicine. This reconstitution
      can be seen in two ways: (i) as a salutary reminder of the extent to which the
      reality even of the human body is constructed; and (ii) as an arena for what
      Stephen Toulmin distinguishes as the "intersection" of natural science and
      history, in which many of philosophy's traditional (and traditionally abstract)
      questions are given concrete and urgent form. This paper begins by examining a
      number of dualities between the medical body and the body familiar in daily
      experience. Toulmin's epistemological analysis of clinical medicine as combining
      both universal and existential knowledge is then considered. Their expression, in
      terms of attention, respectively, to natural science and to personal history, is
      explored through the epistemological contrasts between the medical body and the
      familiar body, noting the traditional philosophical questions which they in turn
      illustrate.

PMID- 11334377
TI  - The diving bell meets the butterfly: identity lost and re-membered.
AB  - Jean Dominique Bauby, former editor of Elle, suffered a stroke to his brain stem
      that left him with locked-in syndrome. Subsequently, through blinking his left
      eye, he writes his memoir of this experience, The Diving Bell and the Butterfly.
      This paper explores the meaning of embodiment, especially as one's body bears
      upon one's personal identity. It explores the various challenges and threats to
      selfhood that result from Bauby's experience and recounts how Bauby rises to the
      challenge through his memory and imagination.

PMID- 11334378
TI  - The embodiment of birth.
AB  - This paper rejects dualism between mind and body to view the self as an embodied
      biological entity. Rather than seeing the body operating by passive mechanisms as
      Descartes argues, it holds it actively moves in and even defines its world.
      Carrying this perspective to medicine presents an attempt to incorporate or work
      with internal processes of the body; it is sensitive to how patients identify
      with their bodies. The current discussion over the extent to which women should
      try to have natural childbirths provides a concrete example of the differences
      between mechanistic and embodied approaches to medicine.

PMID- 11334379
TI  - The dance: essence of embodiment.
AB  - An analysis of movement, and particularly of dance, helps us to see in an
      extraordinarily effective way the meaning of embodiment. This paper then looks
      through the eyes of dance theorists and at philosophers who consider dance and
      movement and their meaning of embodiment. A study of movement and dance
      encompasses the fullest meaning of embodiment: that the embodied way of being-in
      the-world is also an embedded way of being in a world of others. Dance has
      critically important social ramifications. In our own and other cultures, dance
      plays an important role in healing and in health enhancement.

PMID- 11334380
TI  - Chinese herbs nephropathy: a variant form in Japan.

PMID- 11334381
TI  - Systemic manifestations in Sjogren's syndrome.

PMID- 11334382
TI  - Enigma of alpha1-antitrypsin: alpha1-antitrypsin deficiency reveals a puzzling
      physiological function.

PMID- 11334383
TI  - Diabetic amyotrophy or proximal diabetic neuropathy an immune-mediated condition?

PMID- 11334384
TI  - Apoptosis in autoimmune diseases.
AB  - Over the past decade, our understanding of apoptosis, or programmed cell death,
      has increased greatly, with the identification of some of the major components of
      the apoptotic program and the processes regulating their activation. Although
      apoptosis is an intrinsic process present in all cells, it can be regulated by
      extrinsic factors, including growth factors, cell surface receptors, cellular
      stress and hormones. Apoptotis plays an important role in autoimmune diseases.
      Normal thyrocytes could induce apoptosis of infiltrating activated T cells and
      protect against attack by such cells, i.e., the normal thyroid tissues act as an
      immune privileged site. In Hashimoto's thyroiditis (HT), Fas-mediated apoptosis
      of thyrocytes in a section of tissues is due to at least two separate mechanisms,
      the first by infiltrating activated T cells, and the other by FasL-positive
      thyrocytes in a suicidal or fratricidal fashion. A common feature of autoimmune
      diseases such as systemic lupus erythematosus (SLE) is the breakdown of tolerance
      of self antigens, a consequence of which is the production of autoantibodies
      reactive with multiple self proteins. Evidence is accumulating that modifications
      of autoantigens during apoptosis lead to the development of autoantibodies by
      bypassing the normal mechanisms of tolerance. Tissue homeostasis is maintained
      through a balance between cell proliferation and apoptotic cell death. Rheumatoid
      arthritis (RA) is characterized by pronounced hyperplasia of the synovial tissue,
      cell infiltration and periarticular osteoporosis. Enhanced Bcl-2 expression and
      NF-kappaB nuclear translocation of synovial cells are induced by inflammatory
      cytokines and/or growth factors. These synovial cells become resistant toward
      apoptosis triggered by various stimuli. The infiltrated cells which are defect in
      activation-induced cell death can cause autoimmunity by allowing the survival of
      autoreactive T and B cells. These data suggest that apoptosis might be implicated
      with the pathogenesis of autoimmunity, whereas the mechanisms might be distinct
      in each autoimmune disease.

PMID- 11334385
TI  - Endothelin in renal diseases and cardiovascular remodeling in renal failure.
AB  - The pathogenetic mechanisms leading to progression of renal failure are only
      partly understood. Several studies in immune- and non-immune-mediated models of
      renal damage have recently implicated the endothelin (ET) system as a major
      player in these processes. In animal models, ET receptor antagonists have been
      shown to be highly effective in abrogating the progression of renal failure.
      Furthermore, cardiac structural alterations seen in hypertension and/or renal
      insufficiency, e.g. left ventricular hypertrophy, thickening of intramyocardial
      arterioles, and the increase in non-vascular interstitial tissue, are largely
      prevented by ET receptor antagonists. In this context it is of interest that
      these beneficial renal and cardiac effects are, at least in most studies,
      independent of systemic blood pressure. In addition to the specific
      pharmacological blockade of the renin-angiotensin system [ACE inhibitors,
      angiotensin II receptor (AT1) antagonists], blockade of ET receptors or ET
      converting enzyme (ECE) may be a new tool to interfere with progression of renal
      failure and cardiovascular remodeling in humans.

PMID- 11334386
TI  - Evaluation of recurrence in 36 subacute thyroiditis patients managed with
      prednisolone.
AB  - OBJECTIVE: The incidence of subacute thyroiditis (SAT) is low and there are a few
      reports of recurrence of subacute thyroiditis. Current treatment protocols for
      SAT are not uniform. Prednisolone (PSL) is chosen more often for treatment than
      nonsteroidal anti-inflammatory drugs. This study was undertaken to confirm the
      recurrence rate of SAT managed by PSL, and to compare the initial laboratory data
      between the recurrent and the non-recurrent groups. METHODS: After diagnosis, all
      patients were treated with PSL (starting at 30 mg or 25 mg per day, tapered by 5
      mg per week) for 5 or 6 weeks. We evaluated data and symptoms at the first visit
      and during the therapy. PATIENTS: Thirty-six patients who received only PSL for
      SAT at our hospital between January 1997 and December 1998 were referred. These
      patients asked to visit every 2 weeks for the monitoring of symptoms and
      laboratory data. RESULTS: SAT symptoms recurred in eight patients (22%), most
      upon cessation of PSL. There was no difference in initial serum sialic acid,
      erythrocyte sedimentation rate, C-reactive protein, thyroglobulin, serum free
      thyroxine and free triiodothyronine before PSL treatment between the recurrent
      and non-recurrent patient populations. CONCLUSIONS: The recurrence rate of SAT
      with treated PSL is about 20%. There was no difference in the laboratory data
      before starting the therapy between recurrent and non-recurrent groups.
      Therefore, a modified protocol of PSL administration may be needed to decrease
      the early recurrent rate of SAT.

PMID- 11334387
TI  - Outbreak of Chinese herb nephropathy in Japan: are there any differences from
      Belgium?
AB  - OBJECTIVE: The purpose of this article was to study and clarify the features of
      Chinese herb nephropathy (CHN) in Japan. PATIENTS AND METHODS: The subjects
      consisted of patients diagnosed as having CHN in Saiseikai Nakatsu Hospital and
      of those reported in the literature in Japan. We investigated the clinical and
      histological features of CHN patients in Japan and compared them with the Belgian
      cases. RESULTS: The remarkable differences were as follows: (1) high prevalence
      in males compared with Belgian cases, (2) Fanconi syndrome was found in most
      cases, (3) no patients had malignant tumors in the urinary tract. In addition,
      the ascribed Chinese medicines in Japan were divided into three groups: 'Tenshin
      toki-shigyaku-ka-gosyuyu-syokyo-to', 'Boui-ougi-to', and others. CONCLUSION: CHN
      in Japan has some characteristics distinguished from Belgian nephropathy. One
      hypothesis is a susceptibility to aristolochic acids (AAs), which is considered
      to be a causative agent, may be different among races. Another is that there
      could be some other toxic substances affecting the clinical findings although
      they are not identified at present. Further studies must be undertaken to clarify
      these differences.

PMID- 11334388
TI  - Gastrointestinal stromal tumor with a novel mutation of KIT proto-oncogene.
AB  - The majority of human gastrointestinal mesenchymal tumors are gastrointestinal
      stromal tumors (GISTs). Recent reports have shown the existence of gain-of
      function mutations in the juxta-membrane domain of receptor tyrosine kinase (KIT)
      in GISTs. We present a 77-year-old woman with GIST diagnosed by positive
      immunostaining of cluster designation (CD) 34 and KIT. This case had a novel
      mutation at codon 576 located in the juxta-membrane domain of KIT. Our results
      indicate the importance of mutations in this KIT region and suggest the
      possibility of the existence of other types of mutations in this region in GISTs.

PMID- 11334389
TI  - Anorexia nervosa with ischemic necrosis of the segmental ileum and cecum.
AB  - A 41-year-old woman with long-standing anorexia nervosa showed paralytic ileus
      and serum creatine kinase elevation. Surgical treatment showed necrosis of the
      segmental ileum and cecum with perforation. She died of septic shock 3 days after
      the operation. Postmortem examination revealed no occlusion of the superior
      mesenteric artery or its main branches, and no arteriosclerotic changes.
      Histological examinations confirmed non-occlusive mesenteric infarction. This
      case suggested that necrosis of bowels might have been caused by poor blood
      supply due to severe malnutrition and dehydration for many years, which could be
      one of the fatal complications of anorexia nervosa.

PMID- 11334390
TI  - Autoimmune hepatitis concomitant with hypergammaglobulinemic purpura, immune
      thrombocytopenia, and Sjogren's syndrome.
AB  - Sjogren's syndrome occurs as an occasional complication of autoimmune hepatitis,
      and purpura or thrombocytopenia develops in some patients with this syndrome.
      This report describes a 62-year-old woman with a 6-year history of autoimmune
      hepatitis who concurrently had hypergammaglobulinemic purpura, immune
      thrombocytopenia and Sjogren's syndrome. Treatment with prednisolone resulted in
      marked improvement of biochemical, hematological and dermatological
      abnormalities. This case emphasizes the manifestation of purpura or
      thrombocytopenia as an associated disorder during the course of autoimmune
      hepatitis concomitant with Sjogren's syndrome.

PMID- 11334391
TI  - Extensive myocardial stunning showing transient regression of prolonged T wave
      inversion and prolonged sympathetic denervation.
AB  - A 69-year-old woman was admitted to the hospital with palpitations. Although left
      ventriculography showed extensive akinesis except in the basal hyperkinetic
      segment, coronary angiography showed normal coronary arteries. 123I
      metaiodobenzylguanidine (MIBG) accumulation was obviously reduced in the
      anteroseptal, apical and inferior areas. Inverted T waves developed on day 3 and
      disappeared on day 104 after transient regression. Echocardiography showed normal
      left ventricular motion two weeks later. Ergonovine provocation test showed no
      vasospasm and thallium-201 showed no perfusion defect on day 46.
      Electrocardiography and MIBG returned to normal on day 216. These findings
      suggest prolonged sympathetic nerve injury in extensive myocardial stunning.

PMID- 11334392
TI  - Acute gastric dilatation accompanied by diabetes mellitus.
AB  - A 72-year-old man with diabetic triopathy was hospitalized with methicillin
      resistant staphylococcus aureus pneumonia. Six hours after the admission, his
      abdomen was fully expanded. An abdominal X-ray showed gastric dilatation. After
      insertion of a gastric tube to extract gastric air, his abdomen was flat and
      gastric dilatation improved. A positive Schellong test and decreased coefficient
      of RR interval in electrocardiogram variation indicated autonomic neuropathy,
      which may explain the reason for gastric hypomotility. Acute gastric dilatation
      in this patient may have occurred due to gastric hypomotility as a result of
      diabetic autonomic neuropathy in addition to gastric motility inhibition
      resulting from gastric autonomic nerve stimulation by bacterial toxin.

PMID- 11334393
TI  - Insulin and somatostatin releasing islet cell tumor caused hypoglycemia.
AB  - We report a hypoglycemic case with normal insulin levels, which was caused by an
      islet cell tumor that was releasing insulin and somatostatin. A fasting test
      suggested the over secretion of insulin. Moreover, this hypoglycemia was enhanced
      by the inhibitory effect of somatostatin on the secretion of insulin counter
      regulatory hormones, such as glucagon, in addition to the autonomous secretion of
      insulin from the tumor. In cases of hypoglycemia with apparently normal insulin
      levels, the measurement of somatostatin and various provocative tests are
      recommended. Arterial stimulation venous sampling (ASVS) was useful to detect the
      location of this functioning islet cell tumor.

PMID- 11334394
TI  - Allopurinol hypersensitivity syndrome associated with systemic cytomegalovirus
      infection and systemic bacteremia.
AB  - A 43-year-old man developed fever, skin rash, eosinophillia, and severe renal and
      liver dysfunction following treatment with allopurinol. The patient died after 3
      months of hospitalization. Autopsy revealed systemic cytomegalovirus infection
      and bacteremia.

PMID- 11334395
TI  - Compound heterozygosity for alpha-1-antitrypsin (S(iiyama) and QO(clayton)) in an
      Oriental patient.
AB  - Alpha-1-antitrypsin (alpha1AT) deficiency is extremely rare among Orientals. We
      treated a 37-year-old man with severe pulmonary emphysema associated with a low
      serum concentration of alpha1AT. Mutation analysis of the alpha1AT gene was
      performed using a reverse transcription-polymerase chain reaction followed by
      sequencing. The patient proved to be a compound heterozygote carrying a S(iiyama)
      deficient allele and a QO(clayton) null allele. This is the first Japanese case
      of alpha1AT deficiency to arise from such compound heterozygosity in a family
      with no apparent consanguineous marriage, suggesting that the gene frequency for
      deficient alleles might be somewhat higher than previously estimated.

PMID- 11334398
TI  - Intravenous immunoglobulin therapy for diabetic amyotrophy.
AB  - A 49-year-old woman with diabetes mellitus developed progressive weakness and
      atrophy of both thighs rendering her wheelchair-bound within two months. The
      neurological findings and electrophysiological test results were compatible with
      diabetic amyotrophy (DA). Immediately after intravenous immunoglobulin (IVIg)
      therapy (20 g x 3 days), she became able to walk with a cane. After the next
      course of the therapy, she could walk without assistance. This dramatic effect of
      IVIg therapy together with the recent observation of vasculitic neuropathy in DA
      indicates an inflammatory process in this condition, and gives support to this
      treatment for DA.

PMID- 11334396
TI  - Hypoglycemia induced by secretion of high molecular weight insulin-like growth
      factor-II from a malignant solitary fibrous tumor of the pleura.
AB  - A 49-year-old woman with a malignant solitary fibrous tumor of the pleura
      presented with hypoglycemia. Most of the serum insulin-like growth factor II (IGF
      II) existed as high molecular weight IGF-II. Furthermore, there were larger
      amounts of high molecular weight IGF-II found in the tumor cystic fluid than in
      the serum. After surgical resection of the tumor, high molecular weight IGF-II
      was not detected in the serum and the hypoglycemia resolved.
      Immunohistochemically, IGF-II was localized in the so-called Golgi area of the
      tumor cell. These findings suggest that hypoglycemia in this patient was caused
      by the high molecular weight IGF-II produced by the tumor.

PMID- 11334397
TI  - Fulminant Mycoplasma pneumoniae pneumonia.
AB  - A 64-year-old woman, who was previously in good health was admitted because of
      progressive respiratory distress. Her chest radiograph revealed bilateral
      widespread alveolar infiltrates. She was given a diagnosis of pneumonia caused by
      Mycoplasma pneumoniae serologically, acute respiratory distress syndrome, and
      disseminated intravascular coagulation. She died of multiple organ failure
      despite intensive therapy with mechanical ventilation, intravenous erythromycin
      and corticosteroids, continuous hemodiafiltration, and plasma exchange. Although
      Mycoplasma pneumoniae infection is usually a benign self-limited disease, this
      case emphasizes its potentially serious nature even in normal healthy
      individuals.

PMID- 11334399
TI  - Development of severe longitudinal atrophy of thoracic spinal cord following
      lupus-related myelitis.
AB  - A 26-year-old woman suffered from acute myelitis at Th 6 level associated with
      systemic lupus erythematosus. Methyl-prednisolone pulse therapy, intravenous high
      dose immunoglobulin administration and plasmapheresis were not effective. Her
      neurological signs had persisted in spite of subsequent administration of oral
      prednisolone and azathiopurine. Magnetic resonance imaging (MRI) of spinal cord
      at the onset showed a marked swelling with intramedullary high intensity signals
      on T2WI along the whole thoracic cord. Three years later, MRI demonstrated a
      severe longitudinal and segmental atrophy of the mid to low thoracic cord which
      resulted in transverse spinal signs.

PMID- 11334400
TI  - Multiple sclerosis with caudate lesions on MRI.
AB  - A 31-year-old woman displayed sleepiness and impairment of recent memory. T2
      weighted MRI revealed high signal intensity lesions in the bilateral basal
      ganglia, thalamus, and brainstem. Although remission was achieved with
      corticosteroid therapy, she again displayed memory dysfunction and emotional
      disturbance one year later, at which time MRI disclosed new lesions in the right
      caudate nucleus and left frontal white matter. Corticosteroid therapy lead to
      improvement, and she suffered no recurrence on maintenance steroid therapy. These
      findings suggest that caudate lesions do occur in multiple sclerosis, the
      manifestations of which can be abulia and memory dysfunction, as in the present
      case.

PMID- 11334401
TI  - Mixed connective tissue disease associated with von Recklinghausen's
      neurofibromatosis.
AB  - We report a 42-year-old Japanese woman with Recklinghausen's neurofibromatosis 1
      (NF1) who developed mixed connective tissue disease (MCTD). Previously
      experiencing good health without an increase in subcutaneous nodules, she
      presented with Raynaud's phenomenon, swollen hands and polyarthralgia Clinical
      examination revealed a high titer of anti-RNP antibody, and she was thus
      diagnosed as having MCTD. She was treated with oral prednisolone (10 mg/day) and
      her symptoms improved rapidly. Since the association of MCTD and NF1 has not been
      reported previously, we concluded that this association is rare. We also
      discussed the association of NF1 and autoimmune diseases including MCTD.

PMID- 11334402
TI  - Defective glucose-dependent insulinotropic polypeptide receptor expression in
      diabetic fatty Zucker rats.
AB  - Glucose-dependent insulinotropic polypeptide (GIP) is a peptide hormone that is
      released postprandially from the small intestine and acts in concert with
      glucagon-like peptide (GLP)-1 to potentiate glucose-induced insulin secretion
      from the pancreatic beta-cell. In type 2 diabetes, there is a decreased
      responsiveness of the pancreas to GIP; however, the insulin response to GLP-1
      remains intact. The literature suggests that the ineffectiveness of GIP in type 2
      diabetes may be a result of chronic homologous desensitization of the GIP
      receptor. Yet, there has been no conclusive evidence suggesting that GIP levels
      are elevated in diabetes. The hypothesis of the present study is that one cause
      of decreased responsiveness to GIP in type 2 diabetes is an inappropriate
      expression of the GIP receptor in the pancreatic islet. This hypothesis was
      tested using a strain of diabetic fatty Zucker rats. The obese rats displayed
      basal GIP levels similar to the control animals; however, they were unresponsive
      to a GIP infusion (4 pmol.min(-1). kg(-1)), whereas the lean animals displayed a
      significant reduction in blood glucose (GIP levels, 50% control after 60 min, P <
      0.05) as well as a significant increase in circulating insulin. GIP also potently
      stimulated first-phase insulin secretion from isolated perifused islets (10.3 +/-
      3.0 x basal), and GIP and GLP-1 potentiated insulin secretion from the perfused
      pancreas (6 x control area under the curve [AUC]) from lean animals. GIP yielded
      no significant effect in the Vancouver diabetic fatty Zucker (VDF) rat
      pancreases, whereas GLP-1 elicited an eightfold increase of insulin secretion
      from the perfused VDF pancreas. Islets from lean animals subjected to static
      incubations with GIP showed a 2.2-fold increase in cAMP, whereas GIP failed to
      increase islet cAMP in the VDF islets. Finally, the expression of both GIP
      receptor mRNA and protein was decreased in islets from VDF rats. These data
      suggest that the decreased effectiveness of GIP in the VDF rat and in type 2
      diabetes may be a result of a decreased receptor expression in the islet.

PMID- 11334403
TI  - Ca2+-dependent exocytosis of L-glutamate by alphaTC6, clonal mouse pancreatic
      alpha-cells.
AB  - Pancreatic islet cells express receptors and transporters for L-glutamate and are
      thus believed to use L-glutamate as an intercellular signaling molecule. However,
      the mechanism by which L-glutamate appears in the islets is unknown. In the
      present study, we investigated whether L-glutamate is secreted through exocytosis
      by alphaTC6 cells (clonal mouse pancreatic alpha-cells). An appreciable amount of
      L-glutamate was released from cultured cells after the addition of KCl or A23187
      in the presence of Ca2+ and 10 mmol/l glucose in the medium. The KCl-induced
      glutamate release was significantly reduced when assayed in the absence of Ca2+
      or when the cells were pretreated with EGTA-AM. The KCl-induced Ca2+-dependent
      glutamate release was inhibited approximately 40% by voltage-gated Ca2+ channel
      blockers, such as nifedipine at 20 micromol/l. The degree of KCl-induced Ca2+
      dependent glutamate release was correlated with an increase in intracellular
      [Ca2+], as monitored by fura-2 fluorescence. Botulinum neurotoxin type E
      inhibited 55% of the KCl-induced Ca2+-dependent glutamate release, followed by
      specific cleavage of 25 kDa synaptosomal-associated protein. Furthermore,
      bafilomycin A1, a specific inhibitor of vacuolar H+-ATPase, inhibited 40% of the
      KCl-induced Ca2+-dependent glutamate release. Immunoelectronmicroscopy with
      antibodies against synaptophysin, a marker for neuronal synaptic vesicles and
      endocrine synaptic-like microvesicles, revealed a large number of synaptophysin
      positive clear vesicles in cells. Digitonin-permeabilized cells took up L
      glutamate only in the presence of MgATP, which is sensitive to bafilomycin A1 or
      3,5-di-tert-butyl-4-hydroxybenzylidene-malononitrile (a proton conductor) but
      insensitive to either oligomycin or vanadate. From these results, it was
      concluded that alphaTC6 cells accumulate L-glutamate in the synaptophysin
      containing vesicles in an ATP-dependent manner and secrete it through a Ca2+
      dependent exocytic mechanism. The Ca2+-dependent glutamate release was also
      triggered when cells were transferred in the medium containing 1 mmol/l glucose,
      suggesting that low glucose treatment stimulates the release of glutamate. Our
      results are consistent with the idea that L-glutamate is secreted by alpha-cells
      through Ca2+-dependent regulated exocytosis.

PMID- 11334404
TI  - Beta-cell mass dynamics in Zucker diabetic fatty rats. Rosiglitazone prevents the
      rise in net cell death.
AB  - The evolution of diabetes in the male leptin receptor-deficient (fa/fa) Zucker
      diabetic fatty (ZDF) rat is associated with disruption of normal islet
      architecture, beta-cell degranulation, and increased beta-cell death. It is
      unknown whether these changes precede or develop as a result of the increasing
      plasma glucose, or whether the increased beta-cell death can be prevented. Early
      intervention with thiazolidinediones prevents disruption of the islet
      architecture. To determine the specific effects of rosiglitazone (RSG) on beta
      cell mass dynamics, male fa/fa (obese) and +/fa or +/+ (lean) rats age 6 weeks
      were fed either chow (control group [CN]) or chow mixed with rosiglitazone (RSG
      group) at a dosage of 10 micromol. kg(-1) body wt.day(-1). Rats were killed after
      0, 2, 4, 6, or 10 weeks of treatment (at age 6, 8, 10, 12, or 16 weeks). Plasma
      glucose increased from 8.9 +/- 0.4 mmol/l at 0 weeks to 34.2 +/- 1.8 mmol/l (P =
      0.0001) at 6 weeks of treatment in obese CN rats and fell from 8.0 +/- 0.3 to 6.3
      +/- 0.4 mmol/l in obese RSG rats (P = 0.02). beta-cell mass fell by 51% from 2 to
      6 weeks of treatment (ages 8-12 weeks) in obese CN rats (6.9 +/- 0.9 to 3.4 +/-
      0.5 mg; P < 0.05), whereas beta-cell mass was unchanged in obese RSG rats. At 10
      weeks of treatment (age 16 weeks), beta-cell mass in obese CN rats was only 56%
      of that of obese RSG rats (4.4 +/- 0.4 vs. 7.8 +/- 0.3 mg, respectively; P =
      0.0001). The beta-cell replication rate fell from a baseline value of 0.95 +/-
      0.12% in lean rats and 0.94 +/- 0.07% in obese rats (at 0 weeks) to approximately
      0.3-0.5% in all groups by 6 weeks of treatment (age 12 weeks). After 10 weeks of
      treatment, beta-cell replication was higher in obese RSG rats than in CN rats
      (0.59 +/- 0.14 vs. 0.28 +/- 0.05%, respectively; P < 0.02). Application of our
      mass balance model of beta-cell turnover indicated that net beta-cell death was
      fivefold higher in obese CN rats as compared with RSG rats after 6 weeks of
      treatment (age 12 weeks). The increase in beta-cell death in obese CN rats during
      the 6-week observation period was well correlated with the increase in plasma
      glucose (r2 = 0.90, P < 0.0001). These results suggest that the development of
      hyperglycemia in ZDF rats is concomitant with increasing net beta-cell death.
      beta-cell proliferation compensates for the increased beta-cell loss at a time
      when plasma glucose is moderately elevated, but compensation ultimately fails and
      the plasma glucose levels increase beyond approximately 20 mmol/l. Treatment with
      rosiglitazone, previously shown to reduce insulin resistance, prevents the loss
      of beta-cell mass in obese ZDF rats by maintaining beta-cell proliferation and
      preventing increased net beta-cell death.

PMID- 11334405
TI  - The cephalic insulin response to meal ingestion in humans is dependent on both
      cholinergic and noncholinergic mechanisms and is important for postprandial
      glycemia.
AB  - We studied the mechanisms and physiological relevance of the cephalic insulin
      response to meal ingestion in 12 healthy women (age 63 +/- 0.4 years; BMI 27.7 +/
      1.7 kg/m2). The ganglionic antagonist, trimethaphan, which impairs
      neurotransmission across parasympathetic and sympathetic autonomic ganglia, or
      atropine or saline was given intravenously during the first 15 min after
      ingestion of a standard meal (350 kcal). During saline infusion, insulin levels
      increased during the first 10 min after meal ingestion, whereas the first
      increase in glucose was evident at 15 min. The preabsorptive 10-min insulin
      response was reduced by 73 +/- 11% by trimethaphan (P = 0.009), accompanied by
      impaired reduction of glucose levels from 25 to 60 min after meal ingestion
      (deltaglucose = -1.27 +/- 0.5 [with saline] vs. 0.1 +/- 0.4 mmol/l [with
      trimethaphan]; P = 0.008). This reduction at 25-60 min in glucose levels
      correlated significantly to the 10-min insulin response (r = 0.65, P = 0.024).
      The 10-min insulin response to meal ingestion was also reduced by atropine, but
      only by 20 +/- 9% (P = 0.045), which was lower than the reduction with
      trimethaphan (P = 0.004). The preabsorptive insulin response was not accompanied
      by any increase in circulating levels of gastric inhibitory polypeptide (GIP) or
      glucagon-like peptide 1 (GLP-1). In conclusion, 1) the early preabsorptive
      insulin response to meal ingestion in humans can be largely attributed to
      autonomic activation mediated by noncholinergic and cholinergic mechanisms, 2)
      this cephalic insulin response is required for a normal postprandial glucose
      tolerance, and 3) GIP and GLP-1 do not contribute to the preabsorptive cephalic
      phase insulin response to meal ingestion.

PMID- 11334406
TI  - Increased intracellular calcium is required for spreading of rat islet beta-cells
      on extracellular matrix.
AB  - Rat islet beta-cells spread in response to glucose when attached on the matrix
      produced by a rat bladder carcinoma cell line (804G). Furthermore, in a mixed
      population of cells, it has been observed previously that spread cells secrete
      more insulin acutely in response to glucose, compared with cells that remain
      rounded. These results suggest bi-directional signaling between the islet beta
      cell and the extracellular matrix. In the present study, the role of increased
      intracellular free Ca2+ concentration [Ca2+]i as an intracellular step linking
      glucose stimulation and beta-cell spreading (inside-out signaling) was
      investigated. Purified rat beta-cells were attached to this matrix and incubated
      under various conditions known to affect [Ca2+]i. The effect of glucose on beta
      cell spreading was mimicked by 25 mmol/l KCl (which induces calcium influx) and
      inhibited by diazoxide (which impairs depolarization and calcium entry) and by
      the L-type Ca2+ channel blocker SR-7037. When a 24-h incubation at 16.7 glucose
      was followed by 24 h at 2.8 mmol/l, beta-cells that had first spread regained a
      round phenotype. In the presence of thapsigargin, spreading progressed throughout
      the experiment, suggesting that capture of calcium by the endoplasmic reticulum
      is involved in the reversibility of spreading previously induced by glucose.
      Spreading was still observed in degranulated beta-cells and in botulinum
      neurotoxin E-expressing beta-cells when exocytosis was prevented. In summary, the
      results indicate that increased [Ca2+]i is required for the glucose-induced
      spreading of beta-cells on 804G matrix and that it is not a consequence of
      exocytotic processes that follow elevation of [Ca2+]i.

PMID- 11334407
TI  - Tissue inhibitor of metalloproteinase-1 prevents cytokine-mediated dysfunction
      and cytotoxicity in pancreatic islets and beta-cells.
AB  - In addition to inhibiting matrix metalloproteinase-2 and matrix metalloproteinase
      9 activity, recent studies suggest that tissue inhibitor of metalloproteinase
      (TIMP)-1 may inhibit apoptosis in various cell lines. To address this question in
      pancreatic islets and beta-cells, we treated rat pancreatic islets and INS-1
      cells with a high-dose combination of the cytokines interleukin (IL)-1beta, tumor
      necrosis factor-alpha, and interferon-gamma with or without the addition of TIMP
      1 and TIMP-2 protein. Using flow cytometry, we quantitated DNA fragmentation to
      assess cellular apoptosis and confirmed these observations with DNA laddering
      experiments. Next, we transfected the mouse TIMP-1 gene into INS-1 cells and
      performed Western immunoblotting to demonstrate expression of TIMP-1 protein. We
      treated TIMP-1-expressing INS-1 cells with high-dose cytokines and again used
      flow cytometry to assess DNA fragmentation. We also evaluated the effect of TIMP
      1 on IL-1beta-induced inhibition of glucose-stimulated insulin secretion (GSIS)
      in freshly isolated rat pancreatic islets. Finally, we evaluated the effect of
      TIMP-1 on inducible nitric oxide synthase (iNOS) gene expression and nuclear
      factor (NF)-kappaB activity in INS-1 cells stimulated with high-dose cytokines.
      TIMP-1 but not TIMP-2 prevented cytokine-induced apoptosis and cytokine-mediated
      inhibition of GSIS in rat islets and beta-cells. TIMP-1 mediated these effects by
      inhibiting cytokine activation of NF-kappaB, but it did not affect nitric oxide
      production or iNOS gene expression. Therefore, TIMP-1 may be an ideal gene to
      prevent cytokine-mediated beta-cell destruction and dysfunction in models of type
      1 diabetes and islet transplantation rejection.

PMID- 11334408
TI  - Proteome analysis of interleukin-1beta--induced changes in protein expression in
      rat islets of Langerhans.
AB  - The intracellular molecular events involved in the beta-cell death process are
      complex but poorly understood. Cytokines, e.g., interleukin (IL)-1beta, may play
      a crucial role in inducing this process. Protein synthesis is necessary for the
      deleterious effect of IL-1, and induction of both protective and deleterious
      proteins has been described. To characterize the rather complex pattern of islet
      protein expression in rat islets in response to IL-1, we have attempted to
      identify proteins of altered expression level after IL-1 exposure by 2D gel
      electrophoresis and mass spectrometry. Of 105 significantly changed (i.e., up- or
      downregulated or de novo-induced) protein spots, we obtained positive protein
      identification for 60 protein spots. The 60 identifications corresponded to 57
      different proteins. Of these, 10 proteins were present in two to four spots,
      suggesting that posttranslatory modifications had occurred. In addition, 11 spots
      contained more than one protein. The proteins could be classified according to
      their function into the following groups: 1) energy transduction; 2) glycolytic
      pathway; 3) protein synthesis, chaperones, and protein folding; and 4) signal
      transduction, regulation, differentiation, and apoptosis. In conclusion, valuable
      information about the molecular mechanisms involved in cytokine-mediated beta
      cell destruction was obtained by this approach.

PMID- 11334409
TI  - Overexpressing human lipoprotein lipase in mouse skeletal muscle is associated
      with insulin resistance.
AB  - Lipoprotein lipase (LPL) plays a rate-limiting role in triglyceride-rich
      lipoprotein metabolism and is expressed in most tissues. Overexpression of LPL in
      skeletal muscle has been linked with higher plasma glucose levels suggesting
      insulin resistance (Jensen et al., Am J Physiol 273:R683-R689, 1997). The aim of
      our study was to ascertain whether the overexpression of human LPL in skeletal
      muscle leads to insulin resistance and to investigate the mechanism. Respiratory
      quotient measurements in both transgenic (MCKhLPL) and nontransgenic mice on a
      high-carbohydrate diet were conducted and showed a shift in fuel usage in
      transgenic mice when fasting but not when actively feeding. An increase in
      citrate and glucose 6-phosphate levels in fasted MCKhLPL mice further supports
      this preferential use of lipids. When challenged with an intraperitoneal
      injection of glucose (1 g/kg), MCKhLPL mice had a higher plasma glycemic
      excursion than nontransgenic mice. No differences in insulin response were
      observed between the two groups. Further investigation using hyperinsulinemic
      euglycemic clamps revealed insulin resistance in MCKhLPL mice. Despite signs of
      insulin resistance, there was no associated increase in free fatty acids,
      hypertriglyceridemia, or hyperinsulinemia in MCKhLPL mice. In conclusion, MCKhLPL
      mice are insulin resistant, presumably due to increased delivery of lipoprotein
      derived fatty acids to muscle.

PMID- 11334410
TI  - Altered nephrogenesis due to maternal diabetes is associated with increased
      expression of IGF-II/mannose-6-phosphate receptor in the fetal kidney.
AB  - We have recently demonstrated that the exposure to hyperglycemia in utero impairs
      nephrogenesis in rat fetuses (Amri K et al., Diabetes 48:2240-2245, 1999).
      Diabetic pregnancy is commonly associated with alterations in the IGF system in
      fetal tissues. It has also been shown that both IGF-I and IGF-II are produced
      within developing metanephros and promote renal organogenesis. Therefore, we
      investigated the effect of maternal diabetes on IGFs and their receptors in
      developing fetal rat kidney. Diabetes was induced in pregnant rats by a single
      injection of streptozotocin on day 0 of gestation. We measured the amounts of IGF
      and their receptors, both proteins and mRNAs, in the metanephroi of fetuses
      issued from diabetic subjects and in age-matched fetuses from control subjects
      (14-20 days of gestation). IGF-II was produced throughout fetal nephrogenesis,
      whereas IGF-I protein was not detected, suggesting a critical role of IGF-II in
      kidney development. Fetal exposure to maternal diabetes caused no change in IGF
      production in the early stages of nephrogenesis. Similarly, the amounts of IGF-I
      receptor and insulin receptor were not altered. By contrast, there was an
      increase in production of IGF-II/mannose-6-phosphate receptor throughout
      nephrogenesis. Because this receptor plays an essential role in regulating the
      action of IGF-II, the altered nephrogenesis in fetuses exposed to maternal
      diabetes may be linked to a decrease in IGF-II bioavailability.

PMID- 11334411
TI  - Effect of 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside infusion on in
      vivo glucose and lipid metabolism in lean and obese Zucker rats.
AB  - Activation of AMP-activated protein kinase (AMPK) with 5-aminoimidazole-4
      carboxamide-1-beta-D-ribofurano-side (AICAR) increases glucose transport in
      skeletal muscle via an insulin-independent pathway. To examine the effects of
      AMPK activation on skeletal muscle glucose transport activity and whole-body
      carbohydrate and lipid metabolism in an insulin-resistant rat model, awake obese
      Zuckerfa/fa rats (n = 26) and their lean (n = 23) littermates were infused for 90
      min with AICAR, insulin, or saline. The insulin infusion rate (4 mU.kg(-1).min(
      1)) was selected to match the glucose requirements during AICAR (bolus, 100
      mg/kg; constant, 10 mg.kg(-1).min(-1)) isoglycemic clamps in the lean rats. The
      effects of these identical AICAR and insulin infusion rates were then examined in
      the obese Zucker rats. AICAR infusion increased muscle AMPK activity more than
      fivefold (P < 0.01 vs. control and insulin) in both lean and obese rats. Plasma
      triglycerides, fatty acid concentrations, and glycerol turnover, as assessed by
      [2-13C]glycerol, were all decreased in both lean and obese rats infused with
      AICAR (P < 0.05 vs. basal), whereas insulin had no effect on these parameters in
      the obese rats. Endogenous glucose production rates, measured by [U-13C]glucose,
      were suppressed by >50% during AICAR and insulin infusions in both lean and obese
      rats (P < 0.05 vs. basal). In lean rats, rates of whole-body glucose disposal
      increased by more than two-fold (P < 0.05 vs. basal) during both AICAR and
      insulin infusion; [3H]2-deoxy-D-glucose transport activity increased to a similar
      extent, by >2.2-fold (both P < 0.05 vs. control), in both soleus and red
      gastrocnemius muscles of lean rats infused with either AICAR or insulin. In the
      obese Zucker rats, neither AICAR nor insulin stimulated whole-body glucose
      disposal or soleus muscle glucose transport activity. However, AICAR increased
      glucose transport activity by approximately 2.4-fold (P < 0.05 vs. control) in
      the red gastrocnemius from obese rats, whereas insulin had no effect. In summary,
      acute infusion of AICAR in an insulin-resistant rat model activates skeletal
      muscle AMPK and increases glucose transport activity in red gastrocnemius muscle
      while suppressing endogenous glucose production and lipolysis. Because type 2
      diabetes is characterized by diminished rates of insulin-stimulated glucose
      uptake as well as increased basal rates of endogenous glucose production and
      lipolysis, these results suggest that AICAR-related compounds may represent a new
      class of antidiabetic agents.

PMID- 11334412
TI  - Pioglitazone ameliorates tumor necrosis factor-alpha-induced insulin resistance
      by a mechanism independent of adipogenic activity of peroxisome proliferator-
      activated receptor-gamma.
AB  - Tumor necrosis factor (TNF)-alpha is one of the candidate mediators of insulin
      resistance associated with obesity, a major risk factor for the development of
      type 2 diabetes. The insulin resistance induced by TNF-alpha is antagonized by
      thiazolidinediones (TZDs), a new class of insulin-sensitizing drugs. The aim of
      the current study was to dissect the mechanism whereby pioglitazone, one of the
      TZDs, ameliorates TNF-alpha-induced insulin resistance in 3T3-L1 adipocytes.
      Pioglitazone restored insulin-stimulated 2-deoxyglucose (DOG) uptake, which was
      reduced by TNF-alpha, with concomitant restorations in tyrosine phosphorylation
      and protein levels of insulin receptor (IR) and insulin receptor substrate (IRS)
      1, as well as association of the p85 regulatory subunit of phosphatidylinositol
      (PI) 3-kinase with IRS-1 and PI 3-kinase activity. Adenovirus-mediated gene
      transfer of either wild-type human peroxisome proliferator-activated receptor
      (PPAR)-gamma2 or a mutant carrying a replacement at the consensus mitogen
      activated protein kinase phosphorylation site (hPPAR-gamma2-S112A) promoted
      adipogenesis of 3T3-L1 fibroblasts and restored TNF-alpha-induced decrease of
      triglyceride in adipocytes as effectively as pioglitazone. Overexpression of the
      PPAR-gamma proteins in TNF-alpha-treated adipocytes restored protein levels of
      IR/IRS-1, but did not improve insulin-stimulated tyrosine phosphorylation of
      IR/IRS-1 or insulin-stimulated 2-DOG uptake. These results indicate that the
      ability of pioglitazone to restore insulin-stimulated tyrosine phosphorylation of
      IR/IRS-1, which is necessary for amelioration of TNF-alpha-induced insulin
      resistance, may be independent of the adipogenic activity of PPAR-gamma that
      regulates protein levels of IR/IRS-1.

PMID- 11334413
TI  - Troglitazone induces GLUT4 translocation in L6 myotubes.
AB  - A number of studies have demonstrated that insulin resistance in the skeletal
      muscle plays a pivotal role in the insulin resistance associated with obesity and
      type 2 diabetes. A decrease in GLUT4 translocation from the intracellular pool to
      the plasma membranes in skeletal muscles has been implicated as a possible cause
      of insulin resistance. Herein, we examined the effects of an insulin-sensitizing
      drug, troglitazone (TGZ), on glucose uptake and the translocation of GLUT4 in L6
      myotubes. The prolonged exposure (24 h) of L6 myotubes to TGZ (10(-5) mol/l)
      caused a substantial increase in the 2-deoxy-[3H]D-glucose (2-DG) uptake without
      changing the total amount of the glucose transporters GLUT4, GLUT1, and GLUT3.
      The TGZ-induced 2-DG uptake was completely abolished by cytochalasin-B (10
      micromol/l). The ability of TGZ to translocate GLUT4 from light microsomes to the
      crude plasma membranes was greater than that of insulin. Both cycloheximide
      treatment (3.5 x 10(-6) mol/l) and the removal of TGZ by washing reversed the 2
      DG uptake to the basal level. Moreover, insulin did not enhance the TGZ-induced 2
      DG uptake additively. The TGZ-induced 2-DG uptake was only partially reversed by
      wortmannin to 80%, and TGZ did not change the expression and the phosphorylation
      of protein kinase B; the expression of protein kinase C (PKC)-lambda, PKC-beta2,
      and PKC-zeta; or 5'AMP-activated protein kinase activity. a-Tocopherol, which has
      a molecular structure similar to that of TGZ, did not increase 2-DG uptake. We
      conclude that the glucose transport in L6 myotubes exposed to TGZ for 24 h is the
      result of an increased translocation of GLUT4. The present results imply that the
      effects of troglitazone on GLUT4 translocation may include a new mechanism for
      improving glucose transport in skeletal muscle.

PMID- 11334414
TI  - Effects of tumor necrosis factor-alpha on insulin action in cultured human muscle
      cells.
AB  - Reported discrepancies in the effects of tumor necrosis factor (TNF)-alpha in
      modulating insulin sensitivity of cultured cells may relate both to cell types
      studied and to the time course of exposure to the cytokine. Additionally, the
      relationship of effects on glucose metabolism to changes in the insulin signaling
      pathway cannot be assumed. For in vitro study, the cell type most relevant to
      insulin resistance in humans is the cultured human muscle cell. In the present
      study, TNF brought about no change in the rate of glycogen synthesis in cultured
      human muscle cells unless present during differentiation. The presence of TNF (5
      ng/ml) during the process of differentiation of myoblasts into mature myotubes
      diminished the response of glycogen synthesis to acute insulin stimulation. This
      finding was associated with an impairment of differentiation-dependent increases
      in total cellular glycogen synthase (GS) activity. Under the same conditions of
      TNF exposure, there was no effect on the response to acute insulin stimulation of
      the fractional activity of GS. Similarly, there was no effect on the insulin
      stimulation of protein kinase B (PKB) and inhibition of glycogen synthase kinase
      3 (GSK-3). Acute insulin stimulation brought about a 4.08 +/- 0.44-fold
      stimulation of activity of PKB in the absence of TNF, with 4.81 +/- 0.70-fold
      stimulation in cells exposed to TNF. GSK-3 activity decreased to 74.0 +/- 5.8% of
      basal after insulin stimulation without TNF and 78.3 +/- 5.0% after TNF exposure.
      However, differentiation of myocytes, as defined by an increase in the
      acetylcholine receptor, myogenin, and mature creatine kinase isoform expression,
      was impaired in TNF-treated cells. These studies demonstrate that TNF, if present
      during differentiation, decreases insulin-stimulated rates of storage of glucose
      as glycogen and total GS activity but does not downregulate the insulin-signaling
      system to GS. More generally, TNF also inhibits differentiation of human muscle
      cells in culture.

PMID- 11334415
TI  - Liver-specific igf-1 gene deletion leads to muscle insulin insensitivity.
AB  - Insulin and insulin-like growth factors (IGFs) mediate a variety of signals
      involved in mammalian development and metabolism. To study the metabolic
      consequences of IGF-I deficiency, we used the liver IGF-I-deficient (LID) mouse
      model. The LID mice show a marked reduction (approximately 75%) in circulating
      IGF-I and elevated growth hormone (GH) levels. Interestingly, LID mice show a
      fourfold increase in serum insulin levels (2.2 vs. 0.6 ng/ml in control mice) and
      abnormal glucose clearance after insulin injection. Fasting blood glucose levels
      and those after a glucose tolerance test were similar between the LID mice and
      their control littermates. Thus, the high levels of circulating insulin enable
      the LID mice to maintain normoglycemia in the presence of apparent insulin
      insensitivity. Insulin-induced autophosphorylation of the insulin receptor and
      tyrosine phosphorylation of insulin receptor substrate (IRS)-1 were absent in
      muscle, but were normal in liver and white adipose tissue of the LID mice. In
      contrast, IGF-I-induced autophosphorylation of its cognate receptor and
      phosphorylation of IRS-1 were normal in muscle of LID mice. Thus, the insulin
      insensitivity seen in the LID mice is muscle specific. Recombinant human IGF-I
      treatment of the LID mice caused a reduction in insulin levels and an increase in
      insulin sensitivity. Treatment of the LID mice with GH-releasing hormone
      antagonist, which reduces GH levels, also increased insulin sensitivity. These
      data provide evidence of the role of circulating IGF-I as an important component
      of overall insulin action in peripheral tissues.

PMID- 11334416
TI  - Effect of acute and antecedent hypoglycemia on sympathetic neural activity and
      catecholamine responsiveness in normal rats.
AB  - Adrenergic responsiveness to acute hypoglycemia is impaired after prior episodes
      of hypoglycemia. Although circulating epinephrine responses are blunted,
      associated alterations in adrenal sympathetic nerve activity (SNA) have not been
      reported. We examined adrenal nerve traffic in normal conscious rats exposed to
      acute insulin-induced hypoglycemia compared with insulin with (clamped)
      euglycemia. We also examined adrenal SNA and catecholamine responses to insulin
      induced hypoglycemia in normal conscious rats after two antecedent episodes of
      hypoglycemia (days -2 and -1) compared with prior episodes of sham treatment.
      Acute insulin-induced hypoglycemia increased adrenal sympathetic nerve traffic
      compared with insulin administration with clamped euglycemia (165 +/- 12 vs. 118
      +/- 21 spikes/s [P < 0.05]; or to 138 +/- 8 vs. 114 +/- 10% of baseline [P <
      0.05]). In additional experiments, 2 days of antecedent hypoglycemia (days -2 and
      -1) compared with sham treatment significantly enhanced baseline adrenal SNA
      measured immediately before subsequent acute hypoglycemia on day 0 (180 +/- 11
      vs. 130 +/- 12 spikes/s, respectively; P < 0.005) and during subsequent acute
      hypoglycemia (229 +/- 17 vs. 171 +/- 16 spikes/s; P < 0.05). However, antecedent
      hypoglycemia resulted in a nonsignificant reduction in hypoglycemic
      responsiveness of adrenal SNA when expressed as percent increase over baseline
      (127 +/- 5% vs. 140 +/- 14% of baseline). Antecedent hypoglycemia, compared with
      sham treatment, resulted in diminished epinephrine responsiveness to subsequent
      hypoglycemia. Norepinephrine responses to hypoglycemia were not significantly
      altered by antecedent hypoglycemia. In summary, prior hypoglycemia in normal rats
      increased adrenal sympathetic tone, but impaired epinephrine responsiveness to
      acute hypoglycemia. Hence, these data raise the intriguing possibility that
      increased sympathetic tone resulting from antecedent hypoglycemia downregulates
      subsequent epinephrine responsiveness to hypoglycemia. Alternatively, it is
      possible that the decrease in epinephrine responsiveness after antecedent
      hypoglycemia could be the result of reduced adrenal sympathetic nerve
      responsiveness.

PMID- 11334417
TI  - Circulating  concentrations of the adipocyte protein adiponectin are decreased in
      parallel with reduced insulin sensitivity  during the progression to type 2
      diabetes in rhesus monkeys.
AB  - Adiponectin is an adipose-specific plasma protein whose plasma concentrations are
      decreased in obese subjects and type 2 diabetic patients. This protein possesses
      putative antiatherogenic and anti-inflammatory properties. In the current study,
      we have analyzed the relationship between adiponectin and insulin resistance in
      rhesus monkeys (Macaca mulatta), which spontaneously develop obesity and which
      subsequently frequently progress to overt type 2 diabetes. The plasma levels of
      adiponectin were decreased in obese and diabetic monkeys as in humans.
      Prospective longitudinal studies revealed that the plasma levels of adiponectin
      declined at an early phase of obesity and remained decreased after the
      development of type 2 diabetes. Hyperinsulinemic-euglycemic clamp studies
      revealed that the obese monkeys with lower plasma adiponectin showed
      significantly lower insulin-stimulated peripheral glucose uptake (M rate). The
      plasma levels of adiponectin were significantly correlated to M rate (r = 0.66, P
      < 0.001). Longitudinally, the plasma adiponectin decreased in parallel to the
      progression of insulin resistance. No clear association was found between the
      plasma levels of adiponectin and its mRNA levels in adipose tissue. These results
      suggest that reduction in circulating adiponectin may be related to the
      development of insulin resistance.

PMID- 11334418
TI  - Regulation by insulin of gene expression in human skeletal muscle and adipose
      tissue. Evidence for specific defects in type 2 diabetes.
AB  - Defective regulation of gene expression may be involved in the pathogenesis of
      type 2 diabetes. We have characterized the concerted regulation by insulin (3-h
      hyperinsulinemic clamp) of the expression of 10 genes related to insulin action
      in skeletal muscle and in subcutaneous adipose tissue, and we have verified
      whether a defective regulation of some of them could be specifically encountered
      in tissues of type 2 diabetic patients. Basal mRNA levels (determined by reverse
      transcriptase-competitive polymerase chain reaction) of insulin receptor, insulin
      receptor substrate-1, p85alpha phosphatidylinositol 3-kinase (PI3K),
      p110alphaPI3K, p110betaPI3K, GLUT4, glycogen synthase, and sterol regulatory
      element-binding protein-1c (SREBP-1c) were similar in muscle of control (n = 17),
      type 2 diabetic (n = 9), type 1 diabetic (n = 9), and nondiabetic obese (n = 9)
      subjects. In muscle, the expression of hexokinase II was decreased in type 2
      diabetic patients (P < 0.01). In adipose tissue, SREBP-1c (P < 0.01) mRNA
      expression was reduced in obese (nondiabetic and type 2 diabetic) subjects and
      was negatively correlated with the BMI of the subjects (r = -0.63, P = 0.02).
      Insulin (+/-1,000 pmol/l) induced a two- to threefold increase (P < 0.05) in
      hexokinase II, p85alphaPI3K, and SREBP-1c mRNA levels in muscle and in adipose
      tissue in control subjects, in insulin-resistant nondiabetic obese patients, and
      in hyperglycemic type 1 diabetic subjects. Upregulation of these genes was
      completely blunted in type 2 diabetic patients. This study thus provides evidence
      for a specific defect in the regulation of a group of important genes in response
      to insulin in peripheral tissues of type 2 diabetic patients.

PMID- 11334419
TI  - Effect of experimental elevation of free fatty acids on insulin secretion and
      insulin sensitivity in healthy carriers of the Pro12Ala polymorphism of the
      peroxisome proliferator--activated receptor-gamma2 gene.
AB  - The transcription of many genes involved in lipid metabolism is regulated by the
      peroxisome proliferator-activated receptor-gamma (PPAR-gamma). The Pro12Ala
      polymorphism in the PPAR-gamma2 gene has been associated with reduced
      transcriptional activity in vitro and increased insulin sensitivity in vivo.
      Although PPAR-gamma has been demonstrated in human beta-cells, it is unknown
      whether the Pro12Ala polymorphism plays a role in insulin secretion. Moreover, it
      is also unknown if and how the effect of free fatty acids (FFAs) on insulin
      secretion and insulin sensitivity is modulated by the presence of this
      polymorphism. We therefore performed hyperglycemic clamps (8 mmol/l, 140 min, 5 g
      arginine bolus at min 120) in 10 healthy subjects with the (X/Ala) polymorphism
      and in 10 subjects without the polymorphism (Pro/Pro) basally and after 5 h
      infusion of Intralipid plus heparin. FFA concentrations increased from 473 +/- 61
      micromol/l to 1,732 +/- 163 micromol/l in the Pro/Pro and from 372 +/- 46
      micromol/l to 1,630 +/- 96 micromol/l in the X/Ala group (P = 0.68). Basally,
      neither insulin sensitivity nor insulin secretion were significantly different
      between the two groups. During infusion of Intralipid, first-phase insulin
      secretion remained unchanged in both groups (P = 0.21). In the Pro/Pro group,
      second-phase insulin secretion remained unchanged (444 +/- 67 vs. 471 +/- 93
      pmol/min) and the response to arginine increased from 5,007 +/- 41 to 6,072 +/-
      732 pmol/min. In contrast, in the X/Ala group, there was a decrease of both
      second-phase insulin secretion (533 +/- 58 to 427 +/- 48 pmol/min, P = 0.02 vs.
      Pro/Pro) and in the response to arginine (from 7,518 +/- 1,306 to 6,458 +/- 1,040
      pmol/min, P = 0.014 vs. Pro/Pro). The insulin sensitivity index decreased
      comparably in Pro/Pro and X/Ala (to 71 +/- 8 vs. 74 +/- 9% of basal, P = 0.8). In
      conclusion, these results provide evidence that the Pro12Ala polymorphism in the
      PPAR-gamma2 gene might be involved in a differential regulation of insulin
      secretion in response to increased FFAs in humans.

PMID- 11334420
TI  - Isomer-specific antidiabetic properties of conjugated linoleic acid. Improved
      glucose tolerance, skeletal muscle insulin action, and UCP-2 gene expression.
AB  - Conjugated linoleic acid (CLA) isomers have a number of beneficial health
      effects, as shown in biomedical studies with animal models. Previously, we
      reported that a mixture of CLA isomers improved glucose tolerance in ZDF rats and
      activated peroxisome proliferator-activated receptor (PPAR)-gamma response
      elements in vitro. Here, our aim was to elucidate the effect(s) of specific CLA
      isomers on whole-body glucose tolerance, insulin action in skeletal muscle, and
      expression of genes important in glucose and lipid metabolism. ZDF rats were fed
      either a control diet (CON), one of two CLA supplemented diets (1.5% CLA)
      containing differing isoforms of CLA (47% c9,t11; 47.9% c10,t12, 50:50; or 91%
      c9,t11, c9,t11 isomers), or were pair-fed CON diet to match the intake of 50:50.
      The 50:50 diet reduced adiposity and improved glucose tolerance compared with all
      other ZDF treatments. Insulin-stimulated glucose transport and glycogen synthase
      activity in skeletal muscle were improved with 50:50 compared with all other
      treatments. Neither phosphatidlyinositol 3-kinase activity nor Akt activity in
      muscle was affected by treatment. Uncoupling protein 2 in muscle and adipose
      tissue was upregulated by c9,t11 and 50:50 compared with ZDF controls. PPAR-gamma
      mRNA was downregulated in liver of c9,t11 and pair-fed ZDF rats. Thus, the
      improved glucose tolerance in 50:50 rats is attributable to, at least in part,
      improved insulin action in muscle, and CLA effects cannot be explained simply by
      reduced food intake.

PMID- 11334421
TI  - Thiazolidinediones increase plasma-adipose tissue FFA exchange capacity and
      enhance insulin-mediated control of systemic FFA availability.
AB  - We studied the effects of thiazolidinedione treatment (rosiglitazone 1 or 10
      micromol.kg(-1).day(-1) or darglitazone 1.3 micromol.kg(-1).day(-1) for 3 weeks)
      on lipid metabolism in obese Zucker rats. In the basal 7-h fasted state,
      rosiglitazone (10 micromol.kg(-1).day(-1)) and darglitazone corrected the
      hypertriglyceridemia by increasing plasma triglyceride (TG) clearance and
      decreasing hepatic TG production, as assessed using Triton WR 1339. Free fatty
      acid (FFA) metabolism was assessed using 3H-palmitate tracer by estimating rates
      of plasma FFA appearance (Ra), whole-body FFA oxidation (Rox), and tissue
      specific nonoxidative FFA disposal (Rfs). Basal Ra, plasma FFA levels, and
      clearance were increased by both thiazolidinediones. Detailed studies were
      conducted with darglitazone, which under basal conditions increased Ra (+114%),
      Rox (+51%), and Rfs in adipose tissues. During euglycemic clamps performed at
      insulin levels corresponding to those observed postprandially, darglitazone
      increased the glucose infusion rate from 4.7 to 13.3 mg.min(-1) and, in contrast
      to the basal state, it decreased Ra (-67%), Rox (-84%), and Rfs in adipose
      tissue, muscle, and liver. We concluded that thiazolidinediones 1) ameliorate
      hypertriglyceridemia by lowered hepatic TG production and augmented TG clearance
      (two separate kinetic effects), 2) enhance insulin-mediated suppression of
      systemic FFA mobilization while increasing the capacity to mobilize FFA during
      fasting, 3) increase FFA trafficking into adipose tissue by increasing the
      ability of adipose tissue to take up and store FFA, and 4) enhance metabolic
      flexibility by improving glucoregulation under hyperinsulinemic conditions
      (possibly involving reduced skeletal muscle and liver exposure to fatty acids)
      and augmenting the capacity to utilize FFAs during fasting.

PMID- 11334422
TI  - Troglitazone treatment increases plasma vascular endothelial growth factor in
      diabetic patients and its mRNA in 3T3-L1 adipocytes.
AB  - Troglitazone is one of the thiazolidinediones, a new class of oral antidiabetic
      compounds that are ligands of peroxisome proliferator-activated receptor-gamma.
      This study on vascular endothelial growth factor (VEGF), also known as vascular
      permeability factor, was prompted by our clinical observation that the
      characteristics of troglitazone-induced edema were very similar to those caused
      by vascular hyperpermeability. When Japanese diabetic patients were screened for
      plasma VEGF, we found levels to be significantly (P < 0.001) increased in
      troglitazone-treated subjects (120.1 +/- 135.0 pg/ml, n = 30) compared with those
      treated with diet alone (29.2 +/- 36.1 pg/ml, n = 10), sulfonylurea (25.8 +/-
      22.2 pg/ml, n = 10), or insulin (24.6 +/- 19.0 pg/ml, n = 10). Involvement of
      troglitazone in increased VEGF levels was further supported by the plasma VEGF
      levels in five patients before treatment (20.2 +/- 7.0 pg/ml), after 3 months of
      troglitazone treatment (83.6 +/- 65.9 pg/ml), and 3 months after discontinuation
      (28.0 +/- 11.6 pg/ml). We further demonstrated that troglitazone, as well as
      rosiglitazone, at the plasma concentrations observed in patients, increased VEGF
      mRNA levels in 3T3-L1 adipocytes. VEGF is an angiogenic and mitogenic factor and
      is currently considered the most likely cause of neovascularization and
      hyperpermeability in diabetic proliferative retinopathy. Although increased VEGF
      may be beneficial for subjects with macroangiopathy and troglitazone is currently
      not available for clinical use, vascular complications, especially diabetic
      retinopathy, must be followed with great caution in subjects treated with
      thiazolidinediones.

PMID- 11334424
TI  - Impairment of coronary microvascular dilation in response to cold pressor-
      induced sympathetic stimulation in type 2 diabetic patients with abnormal stress
      thallium imaging.
AB  - Coronary microcirculation dysfunction may be associated with myocardial perfusion
      defects on thallium imaging in diabetic patients without coronary artery
      stenosis. Microvascular coronary adaptation to increased myocardial oxygen demand
      in response to sympathetic stimulation evoked by the cold pressor test was
      examined in 22 type 2 diabetic patients with thallium imaging defects and in 15
      control subjects. Both the diabetic patients and control subjects had
      angiographically normal coronary arteries and no other risk factors. Despite a
      similar increase in the rate-pressure product in the two groups (22.6 +/- 12.4%
      in diabetic patients and 31.8 +/- 8.2% in control subjects, NS), coronary blood
      flow increase in the left anterior descending artery (mean flow velocity measured
      by intracoronary Doppler multiplied by the cross-sectional area measured by
      digital angiography) was significantly lower in diabetic patients than in control
      subjects (14.7 +/- 19.8 vs. 75.5 +/- 13.5%, respectively; P = 0.0001). In
      addition, when there was a positive correlation between the two parameters in
      control subjects (r = 0.651, P < 0.01), there was no relationship in diabetic
      patients (r = 0.054). In conclusion, vasodilation of the coronary
      microcirculation in response to sympathetic stimulation evoked by the cold
      pressor test is impaired in type 2 diabetic patients without epicardial artery
      lesions. This microvascular impairment during sympathetic stimulation may explain
      exercise-induced myocardial perfusion abnormalities observed in these patients
      and may impair microcirculatory coronary vasodilation during current life stress
      episodes such as exercise, mental stress, or cold exposition.

PMID- 11334423
TI  - Upregulation of glucose metabolism during intimal lesion formation is coupled to
      the inhibition of vascular smooth muscle cell apoptosis. Role of GSK3beta.
AB  - The purpose of this study was to define the role of metabolic regulatory genes in
      the pathogenesis of vascular lesions. The glucose transporter isoform, GLUT1, was
      significantly increased in the neointima after balloon injury. To define the role
      of GLUT1 in vascular biology, we established cultured vascular smooth muscle
      cells (VSMCs) with constitutive upregulation of GLUT1, which led to a threefold
      increase in glucose uptake as well as significant increases in both nonoxidative
      and oxidative glucose metabolism as assessed by 13C-nuclear magnetic resonance
      spectroscopy. We hypothesized that the differential enhancement of glucose
      metabolism in the neointima contributed to formation of lesions by increasing the
      resistance of VSMCs to apoptosis. Indeed, upregulation of GLUT1 significantly
      inhibited apoptosis induced by serum withdrawal (control 20 +/- 1% vs. GLUT1 11
      +/- 1%, P < 0.0005) as well as Fas-ligand (control 12 +/- 1% vs. GLUT1 6 +/-
      1.0%, P < 0.0005). Provocatively, the enhanced glucose metabolism in GLUT1
      overexpressing VSMC as well as neointimal tissue correlated with the inactivation
      of the proapoptotic kinase, glycogen synthase kinase 3beta (GSK3beta). Transient
      overexpression of GSK3beta was sufficient to induce apoptosis (control 7 +/- 1%
      vs. GSK3beta 28 +/- 2%, P < 0.0001). GSK3beta-induced apoptosis was significantly
      attenuated by GLUT1 overexpression (GSK3beta 29 +/- 3% vs. GLUT1 + GSK3beta 6 +/-
      1%, n = 12, P < 0.001), suggesting that the antiapoptotic effect of enhanced
      glucose metabolism is linked to the inactivation of GSK3beta. Taken together,
      upregulation of glucose metabolism during intimal lesion formation promotes an
      antiapoptotic signaling pathway that is linked to the inactivation of GSK3beta.

PMID- 11334425
TI  - Cardiomyocyte dysfunction in sucrose-fed rats is associated with insulin
      resistance.
AB  - Diabetes is associated with impaired cardiac dysfunction in both humans and
      animals. Specific phenotypic changes-prolonged action potentials, slowed
      cytosolic Ca2+ clearing, and slowed relaxation-that contribute to this whole
      heart dysfunction occur in isolated ventricular myocytes. The present study was
      designed to determine whether cardiomyocyte abnormalities occur early in the
      development of type 2 diabetes (in this case, insulin resistance) and whether an
      insulin-sensitizing drug (metformin) is cardioprotective. In the study, high
      sucrose feeding was used to induce whole-body insulin resistance. Wistar rats
      were maintained for 7-10 weeks on a starch (ST) diet, sucrose (SU) diet, or diet
      supplemented with metformin (SU + MET). Whole-body insulin resistance was
      measured in SU and SU + MET rats by performing euglycemic-hyperinsulinemic
      clamps. Mechanical properties of isolated ventricular myocytes were measured by
      high-speed video edge detection, and [Ca2+]i transients were evaluated with Fura
      2 AM. Untreated SU rats were insulin-resistant (glucose infusion rate [GIR] =
      14.5 +/- 1.1 mg.kg(-1).min(-1)); metformin treatment in SU + MET rats prevented
      this metabolic abnormality (GIR = 20.0 +/- 2.2 mg.kg(-1).min(-1)). Indexes of
      myocyte shortening and relengthening were significantly longer in SU rats (area
      under the relaxation phase [AR/peak] = 103 +/- 3 msec) when compared to ST and SU
      + MET rats (AR/peak = 73 +/- 2 and 80 +/- 1 msec, respectively). The rate of
      intracellular Ca2+ decay and the integral of the Ca2+ transient through the
      entire contractile cycle were significantly longer in myocytes from SU than from
      ST rats (Ca2+ signal normalized to peak amplitude = 152 +/- 8 vs. 135 +/- 5 msec,
      respectively). Collectively, our data showed the presence of cardiomyocyte
      abnormalities in an insulin-resistant stage that precedes frank type 2 diabetes.
      Furthermore, metformin prevented the development of sucrose-induced insulin
      resistance and the consequent cardiomyocyte dysfunction.

PMID- 11334426
TI  - Diabetic embryopathy in C57BL/6J mice. Altered fetal sex ratio and impact of the
      splotch allele.
AB  - Maternal diabetes (types 1 and 2) induces a broad array of congenital
      malformations, including neural tube defects (NTDs), in humans. One of the
      difficulties associated with studying diabetic embryopathy is the rarity of
      individual malformations. In an attempt to develop a sensitive animal model for
      maternal diabetes-induced NTDs, the present study uses chemically induced
      diabetes in an inbred mouse model with or without the splotch (Sp) mutation, a
      putatively nonfunctional allele of Pax3. Pax3 deficiency has been associated with
      an increase in NTDs. Female C57BL/6J mice, either with or without the Sp allele,
      were injected intravenously with alloxan (100 mg/kg), and plasma glucose was
      measured 3 days later. A wide range of hyperglycemia was induced, and these
      diabetic mice were bred to C57BL/6J males, some carrying the Sp allele.
      Gestational-day-18 fetuses were examined for developmental malformations. Fetuses
      from matings in which either parent carried the Sp allele were genotyped by
      polymerase chain reaction. Maternal diabetes significantly decreased fetal weight
      and increased the number of resorptions and malformations, including NTDs. A
      significant correlation was found between the level of maternal hyperglycemia and
      the malformation rate. The sex ratio for live fetuses in diabetic litters was
      significantly skewed toward male fetuses. Matings involving the Sp allele yielded
      litters with significantly higher percentages of maternal diabetes-induced spina
      bifida aperta but not exencephaly, and this increase was shown to be associated
      with the presence of a single copy of the Sp allele in affected fetuses. Thus,
      Pax3 haploinsufficiency in this murine model of diabetic embryopathy is
      associated with caudal but not cranial NTDs.

PMID- 11334427
TI  - The HLA-DPB1--associated component of the IDDM1 and its relationship to the major
      loci HLA-DQB1, -DQA1, and -DRB1.
AB  - The major histocompatibility complex (MHC) HLA region on chromosome 6p21 contains
      the major locus of type 1 diabetes (IDDM1). Common allelic variants at the class
      II HLA-DRB1, -DQA1, and -DQB1 loci account for the major part of IDDM1. Previous
      studies suggested that other MHC loci are likely to contribute to IDDM1, but
      determination of their relative contributions and identities is difficult because
      of strong linkage disequilibrium between MHC loci. One prime candidate is the
      polymorphic HLA-DPB1 locus, which (with the DPA1 locus) encodes the third class
      II antigen-presenting molecule. However, the results obtained in previous studies
      appear to be contradictory. Therefore, we have analyzed 408 white European
      families (200 from Sardinia and 208 from the U.K.) using a combination of
      association tests designed to directly compare the effect of DPB1 variation on
      the relative predisposition of DR-DQ haplotypes, taking into account linkage
      disequilibrium between DPB1 and the DRB1, DQA1, and DQB1 loci. In these
      populations, the overall contribution of DPB1 to IDDM1 is small. The main
      component of the DPB1 contribution to IDDM1 in these populations appears to be
      the protection associated with DPB1*0402 on DR4-negative haplotypes. We suggest
      that the HLA-DP molecule itself contributes to IDDM1.

PMID- 11334428
TI  - Modest overexpression of neuropeptide Y in the brain leads to obesity after high
      sucrose feeding.
AB  - Neuropeptide Y (NPY), one of the most abundant peptide transmitters in the
      mammalian brain, is assumed to play an important role in feeding and body weight
      regulation. However, there is little genetic evidence that overexpression or
      knockout of the NPY gene leads to altered body weight regulation. Previously, we
      developed NPY-overexpressing mice by using the Thy-1 promoter, which restricts
      NPY expression strictly within neurons in the central nervous system, but we
      failed to observe the obese phenotype in the heterozygote. Here we report that in
      the homozygous mice, overexpression of NPY leads to an obese phenotype, but only
      after appropriate dietary exposure. NPY-overexpressing mice exhibited
      significantly increased body weight gain with transiently increased food intake
      after 50% sucrose--loaded diet, and later they developed hyperglycemia and
      hyperinsulinemia without altered glucose excursion during 1 year of our
      observation period.

PMID- 11334429
TI  - A common stromal cell-derived factor-1 chemokine gene variant is associated with
      the early onset of type 1 diabetes.
AB  - Type 1 diabetes results from the autoimmune destruction of pancreatic beta-cells.
      Although the disease shows a strong association with HLA class II alleles, other
      genes may influence the initiation or the rate of progression of the autoimmune
      process. The recruitment of mononuclear cells within the islets of Langerhans is
      a critical step in the pathogenesis of the disease. Because chemokines are
      cytokines that promote migration of mononuclear cells, we hypothesized that
      polymorphisms in chemokine receptor or chemokine genes, CCR5 and SDF1, may be
      involved in susceptibility to or clinical expression of type 1 diabetes. The
      frequencies of the CCR5-delta32 and SDF1-3'A (801G-->A in the 3' untranslated
      region) variants were similar in 208 unrelated Caucasian patients with type 1
      diabetes and in 120 Caucasian control subjects. They were not modified after
      stratification for the predisposing HLA-DR3 and -DR4 haplotypes. However, the
      SDF1-3'A variant was strongly associated with early onset (< 15 years) of the
      disease (odds ratio 2.6, P = 0.0019). On average, the presence of the SDF1-3'A
      allele was associated with a 5-year reduction in the age at onset of diabetes (P
      = 0.0067). Our results suggest that stromal cell-derived factor-1 may be
      implicated in the aggressiveness of the autoimmune process leading to type 1
      diabetes. These preliminary data require replication in other populations.

PMID- 11334430
TI  - Polymorphism screening of four genes encoding advanced glycation end-product
      putative receptors. Association study with nephropathy in type 1 diabetic
      patients.
AB  - Advanced glycation end-products (AGEs) may play an important role in the
      pathogenesis and progression of cardiovascular and renal complications of
      diabetes. Four putative AGE receptors (RAGEs), AGE-R1, AGE-R2, and AGE-R3 have
      been described. In this study, we scanned the sequence of the genes encoding
      these AGE receptors in 48 patients with type 1 diabetes and investigated the
      identified polymorphisms (n = 19) in 199 type 1 diabetic patients with
      nephropathy and 193 type 1 diabetic patients without nephropathy. Overall, none
      of the polymorphisms was strongly associated with nephropathy. The minor allele
      of a polymorphism located in the promoter region of the RAGE gene (C-1152A)
      conferred a weak protective effect (P < 0.05) and was associated with a longer
      duration of nephropathy-free diabetes (P = 0.08).

PMID- 11334431
TI  - No evidence for linkage or for diabetes-associated mutations in the activin type
      2B receptor gene (ACVR2B) in French patients with mature-onset diabetes of the
      young or type 2 diabetes.
AB  - Activins are members of the transforming growth factor-beta superfamily. They
      have a wide range of biological effects on cell growth and differentiation. For
      transmembrane signaling, activins bind directly to activin receptor type 2A
      (ACVR2A) or 2B (ACVR2B). Transgenic and knock-out mice for the ACVR2B gene
      display various endocrine pancreas-related abnormalities, including islet
      hypoplasia and glucose intolerance, demonstrating the crucial role of ACVR2B in
      the regulation of pancreas development. We have thus examined the contribution of
      this factor to the development of mature-onset diabetes of the young (MODY) and
      type 2 diabetes. No evidence of linkage at the ACVR2B locus has been detected in
      MODY families with unknown etiology for diabetes or found in affected sib pairs
      from families with type 2 diabetes. Mutation screening of the coding sequence in
      MODY probands and in a family with severe type 2 diabetes, including a case of
      pancreatic agenesis, showed single nucleotide polymorphisms that did not
      cosegregate with MODY and were not associated with type 2 diabetes. Our results
      indicate that ACVR2B does not represent a common cause of either MODY or type 2
      diabetes in the French Caucasian population.

PMID- 11334432
TI  - Status of research funded by the American Diabetes Association: year 2.

PMID- 11334433
TI  - Identification of novel cytokine-induced genes in pancreatic beta-cells by high
      density oligonucleotide arrays.
AB  - Type 1 diabetes is an autoimmune disease resulting from the selective destruction
      of insulin-producing beta-cells. Cytokines may contribute to pancreatic beta-cell
      death in type 1 diabetes. beta-cell exposure to interleukin (IL)-1beta induces
      functional impairment, whereas beta-cell culture for 6-9 days in the presence of
      IL-1beta and interferon (INF)-gamma leads to apoptosis. To clarify the mechanisms
      involved in these effects of cytokines, we studied the general pattern of
      cytokine-induced gene expression in beta-cells. Primary rat beta-cells were
      fluorescence-activated cell sorter-purified and exposed for 6 or 24 h to control
      condition, IL-1beta + INF-gamma, or IL-1beta alone (24 h only). Gene expression
      profile was analyzed in duplicate by oligonucleotide arrays. Nearly 3,000
      transcripts were detected in controls and cytokine-treated beta-cells. Of these,
      96 and 147 displayed changes in expression after 6 and 24 h, respectively, of
      exposure to IL-1beta + INF-gamma, whereas 105 transcripts were modified after a
      24-h exposure to IL-1beta. The cytokine-responsive genes were clustered according
      to their biological functions. The major clusters observed were metabolism,
      signal transduction, transcription factors, protein synthesis/ processing,
      hormones, and related receptors. These modifications in gene expression may
      explain some of the cytokine effects in beta-cells, such as decreased protein
      biosynthesis and insulin release. In addition, there was induction of diverse
      cytokines and chemokines; this suggests that beta-cells may contribute to
      mononuclear cell homing during insulitis. Several of the cytokine-induced genes
      are potentially regulated by the transcription factor NF-kappaB. Clarification of
      the function of the identified cytokine-induced gene patterns may unveil some of
      the mechanisms involved in beta-cell damage and repair in type 1 diabetes.

PMID- 11334434
TI  - AMP-activated protein kinase (AMPK) is activated in muscle of subjects with type
      2 diabetes during exercise.
AB  - Insulin-stimulated GLUT4 translocation is impaired in people with type 2
      diabetes. In contrast, exercise results in a normal increase in GLUT4
      translocation and glucose uptake in these patients. Several groups have recently
      hypothesized that exercise increases glucose uptake via an insulin-independent
      mechanism mediated by the activation of AMP-activated protein kinase (AMPK). If
      this hypothesis is correct, people with type 2 diabetes should have normal AMPK
      activation in response to exercise. Seven subjects with type 2 diabetes and eight
      matched control subjects exercised on a cycle ergometer for 45 min at 70% of
      maximum workload. Biopsies of vastus lateralis muscle were taken before exercise,
      after 20 and 45 min of exercise, and at 30 min postexercise. Blood glucose
      concentrations decreased from 7.6 to 4.77 mmol/l with 45 min of exercise in the
      diabetic group and did not change in the control group. Exercise significantly
      increased AMPK alpha2 activity 2.7-fold over basal at 20 min in both groups and
      remained elevated throughout the protocol, but there was no effect of exercise on
      AMPK alpha1 activity. Subjects with type 2 diabetes had similar protein
      expression of AMPK alpha1, alpha2, and beta1 in muscle compared with control
      subjects. AMPK alpha2 was shown to represent approximately two-thirds of the
      total alpha mRNA in the muscle from both groups. In conclusion, people with type
      2 diabetes have normal exercise-induced AMPK alpha2 activity and normal
      expression of the alpha1, alpha2 and beta1 isoforms. Pharmacological activation
      of AMPK may be an attractive target for the treatment of type 2 diabetes.

PMID- 11334435
TI  - Regulation of the pancreatic pro-endocrine gene neurogenin3.
AB  - Neurogenin3 (ngn3), a basic helix-loop-helix (bHLH) transcription factor,
      functions as a pro-endocrine factor in the developing pancreas: by itself, it is
      sufficient to force undifferentiated pancreatic epithelial cells to become islet
      cells. Because ngn3 expression determines which precursor cells will
      differentiate into islet cells, the signals that regulate ngn3 expression control
      islet cell formation. To investigate the factors that control ngn3 gene
      expression, we mapped the human and mouse ngn3 promoters and delineated
      transcriptionally active sequences within the human promoter. Surprisingly, the
      human ngn3 promoter drives transcription in all cell lines tested, including
      fibroblast cell lines. In contrast, in transgenic animals the promoter drives
      expression specifically in regions of ngn3 expression in the developing pancreas
      and gut; and the addition of distal sequences greatly enhances transgene
      expression. Within the distal enhancer, binding sites for several pancreatic
      transcription factors, including hepatocyte nuclear factor (HNF)-1 and HNF-3,
      form a tight cluster. HES1, an inhibitory bHLH factor activated by Notch
      signaling, binds to the proximal promoter and specifically blocks promoter
      activity. Together with previous genetic data, these results suggest a model in
      which the ngn3 gene is activated by the coordinated activities of several
      pancreatic transcription factors and inhibited by Notch signaling through HES1.

PMID- 11334436
TI  - Inhibition of GSK-3 selectively reduces glucose-6-phosphatase and phosphatase and
      phosphoenolypyruvate carboxykinase gene expression.
AB  - A major action of insulin is to regulate the transcription rate of specific
      genes. The expression of these genes is dramatically altered in type 2 diabetes.
      For example, the expression of two hepatic genes, glucose-6-phosphatase and
      PEPCK, is normally inhibited by insulin, but in type 2 diabetes, their expression
      is insensitive to insulin. An agent that mimics the effect of insulin on the
      expression of these genes would reduce gluconeogenesis and hepatic glucose
      output, even in the presence of insulin resistance. The repressive actions of
      insulin on these genes are dependent on phosphatidylinositol (PI) 3-kinase.
      However, the molecules that lie between this lipid kinase and the two gene
      promoters are unknown. Glycogen synthase kinase-3 (GSK-3) is inhibited following
      activation of PI 3-kinase and protein kinase B. In hepatoma cells, we find that
      selectively reducing GSK-3 activity strongly reduces the expression of both
      gluconeogenic genes. The effect is at the level of transcription and is observed
      with induced or basal gene expression. In addition, GSK-3 inhibition does not
      result in the subsequent activation of protein kinase B or inhibition of the
      transcription factor FKHR, which are candidate regulatory molecules for these
      promoters. Thus, GSK-3 activity is required for basal activity of each promoter.
      Inhibitors of GSK-3 should therefore reduce hepatic glucose output, as well as
      increase the synthesis of glycogen from L-glucose. These findings indicate that
      GSK-3 inhibitors may have greater therapeutic potential for lowering blood
      glucose levels and treating type 2 diabetes than previously realized.

PMID- 11334437
TI  - Insulin's effect on synthesis rates of liver proteins. A swine model comparing
      various precursors of protein synthesis.
AB  - Insulin's effect on the synthesis of liver proteins remains to be fully defined.
      Previous studies using various surrogate measures of amino acyl-tRNA have
      reported variable results of insulin's effect on liver protein synthesis. We
      determined the effect of insulin with or without amino acid supplementation on
      the synthesis rates of liver proteins (tissue, albumin, and fibrinogen) using L
      [1-13C]Leu as a tracer in 24 male miniature swine. In addition, we compared the
      isotopic enrichment of different precursors of liver proteins with that of amino
      acyl-tRNA using L-[1-13C]Leu and L-[15N]Phe as tracers. Although liver tissue
      fluid enrichment of [13C]Leu and [15N]Phe and that of plasma
      [13C]ketoisocaproatic acid (KIC) were very similar to that of tRNA, plasma
      isotopic enrichment of both Leu and Phe were substantially higher (P < 0.01) and
      VLDL apolipoprotein-B100 enrichment was lower (P < 0.01) than the respective
      amino acyl-tRNA enrichment. Plasma KIC enrichment most accurately predicted
      leucyl-tRNA enrichment, whereas plasma Leu enrichment was best correlated with
      that of tRNA. Neither insulin alone nor insulin plus amino acid infusion had an
      effect on liver tissue protein synthesis. In contrast, insulin alone decreased
      the albumin synthesis rate, and insulin with amino acids maintained the albumin
      synthesis rate. Insulin with or without amino acids inhibited the fibrinogen
      synthesis rate. These results, based on synthetic rates using amino acyl-tRNA,
      were consistent with those obtained using KIC or tissue fluid Leu or Phe as
      precursor pools. These studies demonstrated that plasma KIC enrichment is a
      convenient and reliable surrogate measure of leucyl-tRNA in liver. We also
      concluded that insulin has differential effects on the synthesis rates of liver
      proteins. Whereas insulin with or without amino acid supplement has no acute
      effect on the synthesis of liver tissue protein, insulin has a substantial
      inhibitory effect on fibrinogen synthesis. In contrast, insulin administration
      along with amino supplement is necessary to maintain albumin synthesis rate.

PMID- 11334438
TI  - Insulin and leptin acutely regulate cholesterol ester metabolism in macrophages
      by novel signaling pathways.
AB  - Leptin is produced in adipose tissue and acts in the hypothalamus to regulate
      food intake. However, recent evidence also indicates a potential for direct roles
      for leptin in peripheral tissues, including those of the immune system. In this
      study, we provide direct evidence that macrophages are a target tissue for
      leptin. We found that J774.2 macrophages express the functional long form of the
      leptin receptor (ObRb) and that this becomes tyrosine-phosphorylated after
      stimulation with low doses of leptin. Leptin also stimulates both
      phosphoinositide 3-kinase (PI 3-kinase) activity and tyrosine phosphorylation of
      JAK2 and STAT3 in these cells. We investigated the effects of leptin on hormone
      sensitive lipase (HSL), which acts as a neutral cholesterol esterase in
      macrophages and is a rate-limiting step in cholesterol ester breakdown. Leptin
      significantly increased HSL activity in J774.2 macrophages, and these effects
      were additive with the effects of cAMP and were blocked by PI 3-kinase
      inhibitors. Conversely, insulin inhibited HSL in macrophages, but unlike
      adipocytes, this effect did not require PI 3-kinase. These results indicate that
      leptin and insulin regulate cholesterol-ester homeostasis in macrophages and,
      therefore, defects in this process caused by leptin and/or insulin resistance
      could contribute to the increased incidence of atherosclerosis found associated
      with obesity and type 2 diabetes.

PMID- 11334439
TI  - The transplanted fetal endocrine pancreas undergoes an inherent sequential
      differentiation similar to that in the native pancreas. An ultrastructural study
      in the pig-to-mouse model.
AB  - This study examines, at the ultrastructural level, whether the fetal porcine
      endocrine pancreas (insulin, glucagon, somatostatin, and pancreatic polypeptide
      [PP]- and islet amyloid polypeptide [IAPP]-containing cells) develops normally
      after transplantation under the kidney capsule in athymic mice. We have thus used
      an in vivo pig-to-mouse model for the differentiation of the endocrine pancreas
      removed from its normal milieu. Islet-like cell clusters (ICCs) were prepared
      from the fetal porcine pancreas as previously described and transplanted under
      the renal capsule of athymic mice. At various times after transplantation, the
      endocrine pancreas was removed and the level of differentiation was compared with
      the native pancreas of the same biological age. At the ultrastructural level,
      several sequential steps could be identified based on the morphology and hormone
      content of the secretory granules of the endocrine cell examined. Applying this
      approach, we could demonstrate that the ontogeny of the transplanted fetal pig
      pancreas follows the same sequential differentiation as the native pancreas. The
      process seems to be under stringent control, apparently directly related to the
      biological age of the tissue, and independent not only of the new environment
      under the kidney capsule but also of the adult and xenogeneic milieu provided
      after transplantation to the athymic nude mouse. Therefore, all four major
      hormone-producing cells seem to develop normally after transplantation when
      compared with the development in the native pancreas. IAPP was produced by the
      pluripotent fetal endocrine cells as well as the adult alpha-, beta-, and delta
      cell granules in the native pancreas; however, in the transplanted pancreas, IAPP
      expression was demonstrated only in beta-cells, delta-cells, and PP cells. No
      IAPP was found in granules of the alpha-cell lineage. The results suggest a
      sequential differentiation of all four major types of islet cells from a common
      pluripotent progenitor cell, which seems to be located in the pancreatic ducts.
      Therefore, the results presented strongly suggest that the ontogeny of the four
      major endocrine islet cells is determined by genetic information carried by the
      progenitor cells and not by the systemic or local environment.

PMID- 11334440
TI  - BB rat thymocytes cultured in the presence of islets lose their ability to
      transfer autoimmune diabetes.
AB  - Thymocytes from adult BB rats can adoptively transfer autoimmune diabetes to
      athymic recipients. It is also known that the development of BB rat T-cells is
      recapitulated in adult thymus organ cultures (ATOCs). Based on these
      observations, we tested the hypothesis that cells capable of the adoptive
      transfer of diabetes would be present in long-term ATOCs but could be rendered
      nondiabetogenic by co-culture with appropriate antigens. We observed that cells
      recovered from adult diabetes-resistant BB (BBDR) rat thymi cultured for up to 14
      days can adoptively transfer disease to athymic WAG-rnu/rnu rats treated with
      polyinosinic: polycytidylic acid and a monoclonal antibody to preclude
      development of ART2a+ regulatory T-cells. Co-culture of adult BBDR thymi in the
      presence of BBDR thyrocytes had no effect on the ability of recovered cells to
      induce diabetes in 70-80% of adoptive recipients. In contrast, co-culture in the
      presence of islets prevented transfer of diabetes, on average, in >90% of
      recipients. Fresh islets, frozen islets, and islets pretreated with
      streptozotocin to deplete insulin were equally effective in preventing diabetes,
      but none prevented insulitis in nondiabetic recipients. Co-culture in the
      presence of islets was not associated with detectable alterations in phenotype or
      in the secretion of gamma-interferon or interleukin-4, either in cultures or in
      cells recovered from adoptive recipients. We conclude that islet antigens
      involved in the initiation of autoimmune diabetes in BB rats may be absent or
      deficient in BB rat thymi. Exposure of ATOCs to exogenous islets may lead to
      deletion or anergy of diabetogenic T-cells or to the positive selection of
      regulatory T-cells.

PMID- 11334441
TI  - Adenovirus early region 3(E3) immunomodulatory genes decrease the incidence of
      autoimmune diabetes in NOD mice.
AB  - The early three (E3) region of the adenovirus (Ad) encodes a number of
      immunomodulatory proteins that interfere with class I major histocompatibility
      mediated antigen presentation and confer resistance to cytokine-induced apoptosis
      in cells infected by the virus. Transgenic expression of Ad E3 genes under the
      rat insulin II promoter (RIP-E3) in beta-cells in nonobese diabetic (NOD) mice
      decreases the incidence and delays the onset of autoimmune diabetes. The immune
      effector cells of RIP-E3/NOD mice maintain the ability to infiltrate the islets
      and transfer diabetes into NOD-scid recipients, although at a significantly
      reduced rate compared with wild-type littermates. The islets of RIP-E3/ NOD mice
      can be destroyed by adoptive transfer of splenocytes from wild-type NOD mice;
      however, the time to onset of hyperglycemia is delayed significantly, and 40% of
      these recipients were not diabetic at the end of the experiment. These findings
      suggest that expression of E3 genes in beta-cells affects both the activation of
      immune effector cells and the intrinsic resistance of beta-cells to autoimmune
      destruction.

PMID- 11334442
TI  - Human anti-CD38 autoantibodies raise intracellular calcium and stimulate insulin
      release in human pancreatic islets.
AB  - CD38 is involved in transmembrane signaling in many cell types; anti-CD38
      autoantibodies have been described in diabetic patients. We tested whether human
      anti-CD38 antibodies possess signaling properties by measuring their ability to
      raise intracellular calcium ([Ca2+]i) using the fluo-3-acetoxymethyl ester method
      in a human-derived T-cell line (Jurkat T-cells, expressing high levels of surface
      CD38) and in dispersed human islet cells from normal donors. In Jurkat T-cells,
      11 of 19 anti-CD38-positive sera raised [Ca2+]i (by > or =20% of baseline),
      whereas no [Ca2+]i-mobilizing activity was found in 27 anti-CD38-negative sera
      (chi2 = 20.5, P < 0.0001). In dispersed human islet cells, 5 of 11 anti-CD38
      positive sera (and none of three anti-CD38-negative sera) raised [Ca2+]i
      significantly. When preincubated with Staphylococcus aureus protein A to remove
      IgG, anti-CD38-positive sera showed a 70 +/- 5% reduction in [Ca2+]i-mobilizing
      activity. Preincubation with CD38-transfected NIH-3T3 fibroblasts, but not with
      mock-transfected NIH-3T3 cells, abolished [Ca2+]i mobilization. In blocking
      experiments, preincubation with nonagonistic anti-CD38 monoclonal antibodies also
      prevented [Ca2+]i mobilization. In cultured human islets, anti-CD38-positive sera
      exhibiting [Ca2+]i-mobilizing activity in Jurkat T-cells (n = 6) significantly
      stimulated insulin release at 3.3 mmol/l glucose (median [interquartile range]
      738 microU/ml [234], P = 0.0001 vs. 320 [52] microU/ml of control), whereas 6
      anti-CD38-positive sera without [Ca2+]i-mobilizing activity and 10 anti-CD38
      negative did not. In further incubations, the five anti-CD38-positive sera
      displaying [Ca2+]i-mobilizing activity in dispersed islet cells significantly
      stimulated insulin release at both 3.3 mmol/l glucose (2.2 +/- 0.3% of insulin
      islet content, P < 0.002 vs. 1.2 +/- 0.1% of control) and 16.7 mmol/l glucose
      (3.7 +/- 0.3 vs. 2.3 +/- 0.3%, P < 0.002). We conclude that human anti-CD38
      autoantibodies with agonistic properties on the CD38 effector system occur in
      nature; in human islets, their [Ca2+]i-mobilizing activity is coupled with the
      ability to stimulate insulin release.

PMID- 11334443
TI  - Chloride channels regulate HIT cell volume but cannot fully account for swelling
      induced insulin secretion.
AB  - Insulin-secreting pancreatic islet beta-cells possess anion-permeable Cl-
      channels (I(Cl,islet)) that are swelling-activated, but the role of these
      channels in the cells is unclear. The Cl- channel blockers 4,4'
      diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) and niflumic acid were
      evaluated for their ability to inhibit I(Cl,islet) in clonal beta-cells (HIT
      cells). Both drugs blocked the channel, but the blockade due to niflumic acid was
      less voltage-dependent than the blockade due to DIDS. HIT cell volume initially
      increased in hypotonic solution and was followed by a regulatory volume decrease
      (RVD). The addition of niflumic acid and, to a lesser extent, DIDS to the
      hypotonic solution potentiated swelling and blocked the RVD. In isotonic
      solution, niflumic acid produced swelling, suggesting that islet Cl- channels are
      activated under basal conditions. The channel blockers glyburide, gadolinium, or
      tetraethylammonium-Cl did not alter hypotonic-induced swelling or volume
      regulation. The Na/K/2Cl transport blocker furosemide produced cell shrinkage in
      isotonic solution and blocked cell swelling normally induced by hypotonic
      solution. Perifused HIT cells secreted insulin when challenged with hypotonic
      solutions. However, this could not be completely attributed to I(Cl,islet)
      mediated depolarization, because secretion persisted even when Cl- channels were
      fully blocked. To test whether blocker-resistant secretion occurred via a distal
      pathway, distal secretion was isolated using 50 mmol/l potassium and diazoxide.
      Under these conditions, glucose-dependent secretion was blunted, but
      hypotonically induced secretion persisted, even with Cl- channel blockers
      present. These results suggest that beta-cell swelling stimulates insulin
      secretion primarily via a distal I(Cl,islet)-independent mechanism, as has been
      proposed for K(ATP)-independent glucose- and sulfonylurea-stimulated insulin
      secretion. Reverse transcriptase-polymerase chain reaction of HIT cell mRNA
      identified a CLC-3 transcript in HIT cells. In other systems, CLC-3 is believed
      to mediate swelling-induced outwardly rectifying Cl- channels. This suggests that
      the proximal effects of swelling to regulate cell volume may be mediated by CLC-3
      or a closely related Cl- channel.

PMID- 11334444
TI  - Prevention and control of influenza. Recommendations of the Advisory Committee on
      Immunization Practices (ACIP).
AB  - This report updates the 2000 recommendations by the Advisory Committee on
      Immunization Practices (ACIP) on the use of influenza vaccine and antiviral
      agents (MMWR 2000;49[No. RR-3]:1-38). The 2001 recommendations include new or
      updated information regarding a) the cost-effectiveness of influenza vaccination;
      b) the influenza vaccine supply; c) neuraminidase-inhibitor antiviral drugs; d)
      the 2001-2002 trivalent vaccine virus strains, which are A/Moscow/10/99 (H3N2)
      like, A/New Caledonia/20/99 (H1N1)-like, and B/Sichuan/379/99-like strains; and
      e) extension of the optimal time period for vaccination through November. A link
      to this report and other information regarding influenza can be accessed at the
      website for the Influenza Branch, Division of Viral and Rickettsial Diseases,
      National Center for Infectious Diseases, CDC at
      <http://www.cdc.gov/ncidod/diseases/flu/fluvirus.htm>.

PMID- 11334445
TI  - Testing bioassessment metrics: macroinvertebrate, sculpin, and salmonid responses
      to stream habitat, sediment, and metals.
AB  - The purpose of this article is to report on the testing of responses of
      multimetric macroinvertebrate and habitat indices to common disturbances to
      streams: stream habitat alteration, excessive sediment, and elevated metals
      concentrations. Seven macroinvertebrate community metrics were combined into a
      macroinvertebrate biotic index (MBI), and 11 channel morphology, riparian, and
      substrate features were combined into a habitat index. Indices were evaluated by
      comparing the habitat results to fish population surveys and comparing the
      macroinvertebrate results to habitat ratings, percent fine sediments measured by
      Wolman pebble counts, and copper concentrations. Macroinvertebrate scores
      decreased with increasing percentages of fine sediments measured either across
      the bankfull or instream channel widths. Macroinvertebrate scores decreased with
      increasing copper. One metric, richness of Ephemeroptera, Plecoptera, and
      Trichoptera (EPT) taxa, was more responsive to both copper and sediment than was
      the multimetric MBI. Habitat scores corresponded well with the age class
      structure of salmonids, but not with that of benthic sculpins. Both salmonid and
      sculpin age classes declined with increasing percentages of fine sediments. The
      decline was graded with the sculpin age classes, whether fine sediments were
      measured across the instream or bankfull channel, whereas salmonids consistently
      responded only to the instream fine sediments.

PMID- 11334446
TI  - Assessment of ground water vulnerability and its application to the development
      of protection strategy for the water supply aquifer in Owerri, Southeastern
      Nigeria.
AB  - Pollution vulnerability of the Owerri regional water supply aquifer was evaluated
      as a basis for developing appropriate protection strategy for the groundwater
      resource. The assessment was accomplished using Legrand, GOD, Siga and DRASTIC
      models. Techniques of the models generally involved parameters rating and point
      count systems, which are based on the evaluation of various parameter in relation
      to their capacity for enhancing or attenuating contaminants in the groundwater
      system. Field and laboratory evaluations of the parameters indicate that the
      Owerri area generally occupies a nearly, flat topography with a relatively high
      groundwater recharge. The area is underlain by predominantly sandy facies in the
      Northern area which grades into gravelly sequences towards the southwest. The
      Southeastern area is distinguished by thick clayey facies that thin westwards
      towards the Owerri metropolis. Effective hydraulic conductivity (Kz) in the
      downward direction ranges from 1.44 x 10(-3) to 5.6 x 10(-9) m s(-1); with the
      upper limits reflecting coarse sands and gravelly units. The amount of clay and
      clay-size particles in the sandy and gravelly units is negligible, suggesting
      that the sorptive capacity of the units is low. Depth to water table decreases
      southwards while hydraulic head gradients vary between 0.09 and 0.22. Groundwater
      occurs in unconfined conditions in most places except in the southeastern zone
      where it is semi-confined due to the presence of a clayey unit. The groundwater
      vulnerability map developed on the basis of the models and several other thematic
      maps shows that the Owerri metropolis and the southwest area of Owerri have high
      vulnerability, indicating groundwater pollution. The existing waste disposal
      sites in these sub-areas should be abandoned and rehabilitated to forstall
      further pollution of the groundwater system. Areas to the North and Southeast of
      Owerri have moderate and low vulnerabilities, respectively, indicating the
      relatively lower sensitivity of the groundwater system in the sub-areas to
      contamination. The lower sensitivity could further be matched with properly
      engineered sanitary landfills in the event of choice of sites, as an additional
      protective strategy for the groundwater system.

PMID- 11334447
TI  - Response of the ascorbate-peroxidase of Selenastrum capricornutum to copper and
      lead in stormwaters.
AB  - The green alga Selenastrum capricornutum expresses a unique ascorbate peroxidase,
      that responds to copper and lead. Attempts were made to test if this peroxidase
      could be used to monitor the levels of copper and lead in natural waters. When S.
      capricornutum was exposed to a stormwater sample, the specific activity of the
      peroxidase in the cell extract was commensurate with the combined copper and lead
      contents in the sample. The peroxidase responses were also correlated with the 96
      hr biomass toxicity assay of S. capricornutum. However, unlike the biomass
      toxicity assay, the peroxidase activity was not affected by the anions in the
      samples. The use of this peroxidase can be used as a marker for testing heavy
      metal toxicity in the water.

PMID- 11334448
TI  - Urban noise--a need for acoustic planning.
AB  - The noise status of growing urban centres of the country are very much required
      to develop acoustic design and planning guidelines for various land use
      classification. An attempt in this direction has been made by measuring noise
      equivalent levels for cities like Delhi, Jamshedpur, Dehradun and Nagpur. The
      choice of Ldn (Day-Night noise level) which is a better descriptor of noise
      quality provides an interesting status of noise in these urban centres. It has
      been observed that maximum percentage of areas in Delhi and Jamshedpur fall under
      moderately severe to very severe noisy conditions as compared to Dehradun and
      Nagpur on the noise rating scale. Ways and means are also considered for
      mitigation of noise.

PMID- 11334449
TI  - Care of older patients.

PMID- 11334450
TI  - A novel approach to knee kinematics.
AB  - We describe our experience with in vivo dynamic fluoroscopy that uses simple 2
      plane video fluoroscopy of subjects performing maneuvers such as deep knee-bends,
      gait, and stair climbing after total knee arthroplasty (TKA). Kinematic analysis
      has evolved from 2-dimensional vector calculations to automated 3-dimensional
      computer-assisted design matching techniques that are accurate to 0.75-mm
      translation and 0.75 degrees rotation and that allow simultaneous determination
      of medial and lateral condyle contact positions. TKAs that retain the posterior
      cruciate ligament (PCL) have consistently shown posterior contact in extension
      and anterior translation with flexion with a large variability among subjects.
      PCL-stabilized implants and mobile bearings with high conformity have posterior
      femoral rollback more consistent with normal knees--which is a function of
      prosthetic geometry. Condylar liftoff and screw-home rotation are typical
      kinematic features of all TKAs.

PMID- 11334451
TI  - The use of modularity in revision total hip replacement.
AB  - A study was undertaken to establish the pattern of components revised in recent
      years during total hip revision to establish how often a modular feature of a
      retained component was used. All total hip revisions performed by the total joint
      service of the University Hospital between 1991 and 1995 were reviewed. Revisions
      involving a surface replacement, endoprosthesis, bipolar stem, or infection were
      excluded because retention of components is not an option in these cases. This
      left 158 cases for review. If a modular femoral or acetabular component was
      retained, it was determined whether a different length of modular head or
      different liner type was replanted, thus using a modular feature of the
      component. The most common pattern of component revision was to revise all
      components, which was done in 77 of 158 cases (48.7%). The second most common
      pattern was to revise a socket and leave the stem in place (53/158, 33.5%). The
      third most common was to revise the stem and leave the socket in place (22/158,
      13.9%). The least common was to retain both the stem and socket and exchange the
      head and liner (6/158, 3.8%). Of the 59 cases in which the stem was retained, a
      modular head of a different length was used in 52 (88%). Of the 28 cases in which
      a socket was retained, a different liner type was used in 14 (50%). The modular
      aspect of the retained component was a valuable asset at the time of revision in
      a high percentage of cases (66/158, 41.8%).

PMID- 11334452
TI  - Role of knee aspiration after resection of the infected total knee arthroplasty.
AB  - Recognizing persistent infection after resection arthroplasty and implantation of
      cement spacers in the infected total knee arthroplasty is often difficult. The
      purpose of this study was to determine whether aspiration of the knee after
      resection arthroplasty is valuable for determining the presence of ongoing
      infection. Thirty-four previously infected knees that were aspirated and cultured
      after resection arthroplasty, implantation of cement spacers, and intravenous
      antibiotics for an average of 6.3 weeks were identified. There were 8 cases of
      persistent infection-none identified on preoperative aspiration. Two preoperative
      cultures were false positive for Staphylococcus epidermidis. Preoperative
      cultures were negative in 32 knees, with 8 false-negative results. The antibiotic
      free interval among all cases averaged 20 days; the cases with false-negative
      results from aspiration had an antibiotic-free interval averaging 11.5 days,
      compared with an average of 26 days among all other cases. Aspiration of knees
      after resection arthroplasty had sensitivity of 0%, positive predictive value of
      0%, and accuracy of 71%. Specificity was 92%, and negative predictive value was
      75%. A negative result from joint aspiration after resection arthroplasty does
      not necessarily rule out the presence of ongoing infection. False-negative
      results may be observed if joint aspiration is not delayed more than 2 to 3
      weeks.

PMID- 11334453
TI  - Failure of bipolar hemiarthroplasty: a retrospective review of 31 consecutive
      bipolar prostheses converted to total hip arthroplasty.
AB  - Bipolar hemiarthroplasty has been widely used for the treatment of femoral neck
      fractures in elderly patients. Outcome studies show excellent results with near
      preoperative ambulation and lasting, painless hip function. However, what has
      only recently been considered is that, in some cases, failure of bipolar
      hemiarthroplasty may be due to wear of the thin, ultra-high-molecular weight
      polyethylene (UHMWPE) insert between the inner and outer bearings of the
      prosthesis with subsequent generation of particulate debris, periprosthetic
      osteolysis, and stem loos ening. We reviewed 31 consecutive bipolar
      hemiarthroplasties converted to total hip arthroplasties by a single surgeon
      between 1986 and 1994. The average time to failure was 38 months. Fifty-six
      percent of the cases showed radiographic evidence of osteolysis around the stem.
      Radiographic migration of the bipolar head of more than 1 mm into the pelvis,
      suggestive of cartilage wear, occurred in 67% of the cases. Among the patients
      with radiographic osteolysis and a loose stem at the time of revision, 92% showed
      a characteristic histiocytic and giant cell reaction to polyethylene particles in
      tissue obtained during surgery. The UHMWPE liners from the retrieved outer shells
      showed an average wear rate of 0.7 mm per year. Recent studies comparing bipolar
      to unipolar hemiarthroplasty show little difference between the two with regard
      to morbidity, mortality, or functional outcome. In light of our findings, it
      might be prudent to reconsider the design and indications for bipolar
      hemiarthroplasty.

PMID- 11334454
TI  - Bending stiffness, torsional stability, and insertion force of cementless femoral
      stems.
AB  - In cementless total hip arthroplasty, increased femoral stem flexibility and
      decreased fracture propensity are desirable characteristics. The slotting and
      tapering of the stem have been introduced to achieve this. These features should
      not, however, be allowed to interfere with the ability of the distal stem to
      provide initial mechanical stability, especially under rotation. This study was
      done to investigate the ability of slotted and tapered stem designs to reduce
      stiffness and insertion force while still maintaining adequate torsional
      strength. The torsional strength, maximum insertion force, and insertional work
      of straight, slotted, and taper stems were measured by inserting each type into
      rigid polyurethane foam and torque testing to failure. Bending stiffness of each
      stem design was calculated using numerical methods. When compared to a straight
      stem, a unislot stem has similar torsional strength, maximum insertional force,
      and work of insertion. The bending stiffness is decreased by 19% to 82% depending
      on the bending direction. A trislot design decreased torque strength by 29%,
      maximal insertion force by 36%, and work by 11%. Bending stiffness was decreased
      by 74% and was not dependent on bending direction. A 0.5-mm taper decreased
      torque strength by 11% and insertional work by 14%. No difference was seen in
      maximum insertional force. We conclude that the design features studied (slots
      and taper) are effective in decreasing stem stiffness and reducing fracture
      propensity.

PMID- 11334455
TI  - Mesenchymal chondrosarcoma of soft tissues of the calf.
AB  - Mesenchymal chondrosarcomas are distinct from conventional and dedifferentiated
      chondrosarcomas and are quite rare, making up less than 2% of all
      chondrosarcomas. We describe a mesenchymal chondrosarcoma of the soft tissues of
      the calf and review the differential diagnosis of this poorly understood entity.

PMID- 11334456
TI  - Two cases of surgically treated hand tendon xanthomas.
AB  - Two cases of sugically treated hand tendon xanthomas are presented. On surgical
      exploration, these xanthomas were found to be intertwined within the extensor
      mechanism. Total excision was not possible because it risked loss of integrity of
      the extensor mechanism. Both patients regained full range of motion and
      experienced no progressive tumor growth at a minimum of 1-year follow-up.

PMID- 11334457
TI  - Bilateral fracture of the tibial shaft with intact fibulae.
AB  - We report the case history, treatment, and follow-up of a 16-year-old girl who
      sustained symmetrical fractures of the right and left tibia without fractures of
      the fibulae. Although a fracture of the tibia with an intact fibula is not an
      uncommon fracture pattern, a bilateral fracture of this type is quite rare, and
      we have been unable to find such a reported case in our review of the literature.
      The management of a fracture of the tibia with an intact fibula is controversial,
      with potential complications of delayed union and varus malunion. For this
      reason, as well as the bilateral nature of the injury, we felt operative
      treatment to be indicated.

PMID- 11334458
TI  - Results of decompression and rotator cuff repair in patients 65 years old and
      older: 6- to 14-year follow-up.
AB  - At an average of 9.2 years after surgery, 47 patients with 51 shoulders who had
      undergone rotator cuff repair and subacromial decompression through an open
      Rockwood 2-stage acromioplasty-type approach were reviewed. All patients were 65
      years or older at the time of their initial index procedure. Results were rated
      by patient satisfaction, the Constant's score, American Shoulder and Elbow
      Surgeons (ASES) Evaluation, and Neer rating. Subjectively, the patients were
      highly satisfied, with a 94.1 overall satisfaction rate. Objectively, the average
      Constant's score was 82 when normalized to the opposite shoulder and age.
      According to the Neer rating scale, there were 20 (39%) excellent, 26 (51%)
      satisfactory, and 5 (10%) unsatisfactory results. When assessing the ASES
      Evaluation, the patients who had undergone an extensile deltotrapezial takedown
      had increased strength in their lateral deltoid as compared with a cohort of
      individuals who had undergone the VY exposure. There was no statistically
      significant difference in subjective or objective results. For the most part,
      open rotator cuff repair and subacromial decompression in older patients has a
      high level of success with respect to pain relief, independent living, and when
      desired, reasonable sports participation.

PMID- 11334459
TI  - Osteitis condensans ilii.

PMID- 11334460
TI  - Erosive oral lichen planus and salivary cortisol.
AB  - Patients with oral lichen planus (OLP) often relate the onset and aggravation of
      oral symptoms to increased levels of stress. Under normal conditions, stress
      induces increased cortisol secretion that counteracts inflammatory reactions. The
      objective of the present study was to assess whether patients with OLP have an
      impaired capacity to elevate their cortisol concentrations as a response to
      stress. Saliva samples were collected for cortisol analysis from 10 OLP patients
      once every 15 min during a 2-h test period. In order to induce stress during a
      part of this test period, the patients were confronted with a computerised device
      specifically developed for the induction of transient stress. A visual analogue
      scale (VAS) and a mood adjective check list (MACL) were used to estimate the
      degree of permanent stress. A control group of patients was matched for age and
      sex. The OLP patients did not present with different stress scores when a
      psychometric test (MACL) was used. No statistically significant correlation
      between cortisol concentration and stress level was observed. Thus, no support
      for an impaired capacity of OLP patients to suppress an immune response through
      cortisol induction in conjunction with experimental stress was revealed.

PMID- 11334461
TI  - Serum antioxidant micronutrient levels in oral lichen planus.
AB  - The aim of this study was to elucidate any association between oral lichen planus
      (OLP) and serum antioxidant micronutrients by a population-based case-control
      study. A total of 9536 subjects were examined, and 62 (58 reticular, 4 atrophic
      and erosive) diagnosed with OLP at referral facilities were compared with four
      controls per case (n=248) selected among disease-free subjects matched for age
      and sex. Serum levels of micronutrients (retinol, alpha-tocopherol,
      zeaxanthin/lutein and cryptoxanthin, lycopene, alpha-carotene and beta-carotene)
      were estimated by the high performance liquid chromatography (HPLC) method. Among
      cases, mean serum retinol level (2.820+/-0.849 micromol/l) was significantly
      higher compared with that of controls (2.562+/-0.735 micromol/l) (P<0.05). No
      significant differences were noted in carotenoid levels examined in this study,
      except for a lower level of lycopene found in atrophic/erosive OLP cases. The
      results of this study suggest that low serum retinol or carotenoid levels are not
      risk factors for occurrence of lichen planus, and any specific benefits of
      antioxidant micronutrients cannot be claimed for this inflammatory disorder.

PMID- 11334462
TI  - Catenin dislocation in oral pemphigus vulgaris.
AB  - Cell-to-cell adhesion is mediated by cadherins (integral membrane proteins),
      which form a complex with catenins (cytoplasmatic proteins). While E-cadherin
      expression has been extensively studied in many human skin diseases, less is
      known about the expression levels of catenins in oral blistering diseases. The
      purpose of this study was to evaluate the role of these proteins in the
      pathogenesis of acantholysis in oral pemphigus vulgaris. We evaluated by
      immunohistochemistry beta- and gamma-catenin expression in 7 cases of oral
      pemphigus vulgaris (PV) at various stages of the disease and, as controls, in 18
      healthy patients. Healthy cases showed, as reported in the literature, a strong
      reactivity with both beta- and gamma-catenins, with the intensity of staining
      progressively decreasing from the spinous to the keratinised layers of
      epithelium, which had a prevalent cellular membrane expression. In PV patients,
      we detected a loss of membrane expression of these molecules with a progressive
      displacement of the signal toward the cytosol and, for gamma-catenin, nuclear
      dislocation, particularly in areas with intense acantholysis.

PMID- 11334463
TI  - Natural immunity in recurrent aphthous ulceration.
AB  - In the present study we investigated immunophenotypes of peripheral blood
      lymphocytes, natural killer (NK) cell activity as well as spontaneous migration,
      ingestion, digestion and antibody-dependent cell-mediated cytotoxicity (ADCC) as
      effector functions of polymorphonuclear neutrophil granulocytes (PMNs) in 51
      patients with acute stage recurrent aphthous ulceration (RAU), during remission,
      and 47 age-matched healthy individuals. Statistically significant lower B
      lymphocyte (CD19) values were found between patients with acute RAU, and those
      during the remission period (P<0.001), when compared with those of the controls.
      Total T-lymphocyte (CD3) percentages were lower in patients with RAU, and also
      during the remission period, when compared with the controls (P<0.001). The
      percentages of CD4 lymphocytes were significantly lower in patients with RAU in
      comparison with those of the controls (P<0.001). T-suppressor cells (CD8) were
      unchanged in all three groups of participants. Significantly lower spontaneous
      migration and ingestion values were found in patients with acute RAU, when
      compared with those of the controls, and during the remission period (P<0.001).
      Digestion values differed insignificantly between the patients with acute RAU and
      during the remission period. During the remission period, digestion values were
      significantly elevated when compared with those of the controls (P<0.05). ADCC
      values were lower during the remission period (P<0.001), when compared with the
      values during acute RAU and with those of the controls. Significantly depressed
      NK activity (P<0.001) was observed in patients with acute RAU, when compared with
      that of the controls. During the remission period, values of NK activity were
      also lower (P<0.001) when compared with those of the controls. These results
      suggest either a specific or nonspecific immunological disorder in patients with
      RAU.

PMID- 11334464
TI  - TGF-beta isoforms and TGF-beta receptors in drug-induced and hereditary gingival
      overgrowth.
AB  - Drug therapy and hereditary factors are two of the main causes of gingival
      overgrowth (GO). Both of these forms of GO are associated with increased
      extracellular matrix production by fibroblasts. Transforming growth factor beta
      (TGF-beta) is an important mediator of wound healing and tissue regeneration,
      which stimulates fibroblasts to produce extracellular matrix materials. The aim
      of this immunohistochemical study was to determine whether there is any altered
      expression of TGF-beta isoforms or its receptors in tissue from patients with
      drug-induced GO (DIGO; n=10) and hereditary gingival fibromatosis (n=10) when
      compared to non-overgrowth tissue (n=10). Compared to control tissues,
      significantly more fibroblasts expressed TGF-beta1 in both DIGO and hereditary
      gingival fibromatosis tissues (P<0.03). Cells expressing TGF-beta2 were present
      at control levels in DIGO but were significantly reduced in hereditary gingival
      fibromatosis (P<0.02). By contrast, the number of TGF-beta3-positive cells was
      the same in overgrowth tissues and controls. However, because of differences in
      total fibroblast densities between groups, there was a proportional increase in
      TGF-beta3 as well as TGF-beta1 expressing cells within both overgrowth
      populations (P<0.0001). Furthermore, representation of the TGF-beta2-positive
      phenotype was reduced in hereditary gingival fibromatosis (P<0.01) but increased
      in DIGO (P<0.005) compared to controls. Absorbance measurements of the positive
      cell populations showed that the level of expression was significantly higher for
      TGF-beta1 in hereditary gingival fibromatosis (P<0.002) and significantly lower
      for TGF-beta3 in DIGO (P<0.03). No significant differences in the numbers of TGF
      betaRI- or RII-positive cells were detected between overgrowth tissues and
      controls. However, there were increases in the proportion of receptor-positive
      cells in the total cell population analysed in overgrowth tissues (P<0.0001).
      These results indicate qualitative and quantitative differences in TGF-beta
      isoform and receptor expression by fibroblasts in gingival overgrowth that may
      contribute to disease pathogenesis.

PMID- 11334465
TI  - Growth factors, extracellular matrix components and cell adhesion molecules
      Warthin's tumor.
AB  - We studied expressions of various growth factors, their receptors, cell adhesion
      molecules and extracellular matrix components in Warthin's tumor of the salivary
      gland with immunohistochemistry and reverse transcriptase-polymerase chain
      reaction (RT-PCR). Various growth factors and their receptors, such as
      transforming growth factor-alpha (TGF-alpha), heparin-binding epidermal growth
      factor-like growth factor (HB-EGF), TGF-beta2, TG-beta3, insulin-like growth
      factor (IGF)-I and -II, vascular endothelial growth factor (VEGF), EGF receptor
      (EGFR), erb-B4, TGF-betaRI and II, Flt and Flk-1 and IGF receptor Ibeta, were
      found in epithelial cells and/or in some lymphoid cells. Fibronectin, laminin,
      collagen type IV and tenascin were found in stroma of the lymphoid tissue.
      Integrins such as alpha3beta1 and beta3, Thy-1, CD44 and VCAM-1 were also
      expressed in epithelial and/or lymphoid cells. These various proteins may
      interact and regulate the proliferation and cell attachment of both epithelial
      and lymphoid components in this unique tumor.

PMID- 11334466
TI  - Establishment of gingival epithelial cell lines from transgenic mice harboring
      temperature sensitive simian virus 40 large T-antigen gene.
AB  - We established two gingival epithelial cell lines (GE1 and GE6), originating from
      transgenic mice harboring the temperature-sensitive simian virus 40 large T
      antigen gene. GE1 and GE6 grew at a permissive temperature (33 degrees C) in a
      pavement arrangement and solely formed multilayers that exhibited morphological
      features similar to those of the stratified oral epithelium, with neither the use
      of stromal equivalents nor feeder layers. Both GE cells underwent apoptosis at a
      non-permissive temperature (39 degrees C). Characteristic keratin peptides,
      keratin 4 and 13, for mucosal epithelium were obviously expressed in the
      suprabasal cells, and keratohyalin granules and involucrin were present in the
      surface flat cells in the multilayered culture. Keratin 10 (one of the markers
      for higher keratinized gingival epithelium) was rarely found in some uppermost
      cells, and filaggrin (a component of keratohyalin granules) appeared sparsely in
      uppermost desquamating cells in the older cultures. These observations indicated
      that GE1 and GE6 cells exhibited the phenotype characterizing nonkeratinized
      sulcular epithelium, which possessed the potency undergoing keratinization in
      such highly stratified cultures as oral gingival epithelium. GE cells increased
      the expression levels of mRNA of interleukin-1beta and tumor necrosis factor
      alpha by the stimulation of lipopolysaccharide and extracellular substances of
      oral streptococci. The GE cell lines thus could serve as an excellent
      experimental system for further studies on the physiology of gingival epithelium
      and corresponding diseases, such as periodontal disease, epithelial hyperplasia,
      and gingival tumors.

PMID- 11334467
TI  - Expression of hMSH2 and hMLH1 proteins of the human DNA mismatch repair system in
      ameloblastoma.
AB  - The human DNA mismatch repair (hMMR) system plays an important role in reducing
      mutation and maintaining genomic stability. The MMR system in human cells is
      composed of at least six genes (hMSH2, hMLH1, hMSH3, hPMS1, hPMS2 and
      GTBP/hMSH6). In particular, hMSH2 and hMLH1 are expressed in human cells that are
      undergoing rapid renewal; their reduced expression has been reported in several
      tumors. We examined the protein expression pattern of hMSH2 and hMLH1 by
      immunohistochemistry in 25 ameloblastomas. All ameloblastomas expressed hMSH2 and
      hMLH1 proteins in the outer layer of epithelial cells. The localization of the
      staining was exclusively nuclear. These data suggest that the development and
      progression of these tumors do not depend on a defect in the hMMR system.

PMID- 11334468
TI  - Detection of cell cycle-related factors in ameloblastomas.
AB  - To determine whether cell cycle regulation or alteration plays a role in
      oncogenesis and cytodifferentiation of odontogenic epithelium, cell cycle-related
      factors, including cyclin D1, p16INK4a, p21(WAF1/Cip1) and p27Kip1 proteins, DNA
      topoisomerase IIalpha and histone H3 mRNA, were examined in 8 tooth germs and 31
      ameloblastomas. Cyclin D1 was expressed in epithelial cells near the basement
      membrane in tooth germs and ameloblastomas, suggesting that this protein
      participates in cell proliferation in odontogenic epithelium. Immunoreactivity
      for p16 protein was observed in most epithelial cells in tooth germs and
      ameloblastomas. Expression of p21 protein was detected in most epithelial cells
      in tooth germs and ameloblastomas, but not in keratinizing or granular cells in
      variants of ameloblastomas. Expression of p27 protein was chiefly found in
      central polyhedral cells and keratinizing cells in tooth germs and
      ameloblastomas. These cyclin-dependent kinase inhibitors were well preserved in
      ameloblastomas as compared with tooth germs, suggesting that the odontogenic
      epithelium is strictly regulated by these factors. The cell cycle phase/cellular
      proliferation markers, DNA topoisomerase IIalpha and histone H3 mRNA, were
      localized in scattered epithelial cells attached to the basement membrane in
      tooth germs and ameloblastomas.

PMID- 11334469
TI  - Ameloblastic fibrosarcoma of the mandible: report of two cases and review of the
      literature.
AB  - Ameloblastic fibrosarcoma (AFS) is a rare malignant odontogenic tumour. To date,
      60 well-documented cases have been published in the English-language literature.
      Two additional cases located in the posterior region of the mandible are
      reported. The relevant clinicopathological features of these cases, as well as
      those previously reported are discussed. Approximately two-thirds of AFS are
      malignant tumors de novo, with an average age of the affected patients being 22.9
      years. This age is lower than the one observed in AFS developing from a pre
      existent benign lesion (mean 33 years). Although regional and distant metastases
      are very infrequent, AFS is a locally aggressive lesion, with 23 (37%) of the
      reported cases having at least one recurrence; 12 patients (19.3%) died of the
      disease. Wide surgical excision with long-term follow-up remains the treatment of
      choice for this neoplasm.

PMID- 11334470
TI  - Family planning in grand multiparous women in Diyarbakir, Turkey, 1998: the
      factors affecting contraceptive use and choice of method.
AB  - Family planning is an important service for preventing maternal deaths. A 3-year
      project on children and maternal health was conducted in suburban areas of the
      Diyarbakir province of Turkey. In this project, volunteer women told women
      resident in the area about family planning as well as other maternal and child
      health-related subjects. Within 3 years, all women were visited at least five
      times and changes in contraceptive use were recorded. A cross-sectional study was
      planned to understand the factors affecting contraceptive use in grand
      multiparous women. A total of 200 grand multiparous women were selected from
      visit cards and various characteristics of these women were evaluated. Odds
      ratios and 95% confidence intervals were calculated using logistic regression
      analyses. The use of contraceptives had increased from 33.5% to 59.5% by the end
      of the 3 years in the 200 women. The main factors affecting contraceptive use
      were misconceptions and concerns about health-related risks, having a child
      younger than 14 years working outside the home to contribute to the household
      income, religious opposition, a gap between the desired and actual number of
      sons, number of previous deaths of children and discussion with the husband about
      family planning.

PMID- 11334471
TI  - Detection of Chlamydia trachomatis in semen and urethral specimens from male
      members of infertile couples in Tunisia.
AB  - The sequelae to infection with Chlamydia trachomatis in women are an established
      cause of tubal infertility. However, little is known about chlamydial infection
      and male infertility. The main objective of this study was to evaluate the
      presence of asymptomatic C. trachomatis infections in urethral and semen
      specimens from the male members of infertile couples by means of four different
      methods: the direct fluorescence antibodies assay, cell culture, the Roche Cobas
      Amplicor polymerase chain reaction, and the presence of chlamydial local IgA
      antibodies by the recombinant antibody-enzyme-linked immunosorbent assay. One or
      more chlamydial infection markers were detected in 42 (45.7%) of the 92 examined
      urethral and semen specimens from the male partners of infertile couples. C.
      trachomatis was detected in 23.9% (22/92) of urethral specimens and in 35.9%
      (33/92) of semen specimens. Although there was a significant correlation between
      the detection of one or more chlamydial infection markers in urethral and semen
      specimens (p = 0.01), no significant correlation was found between the detection
      of C. trachomatis DNA in these samples. Furthermore, no significant association
      was found between the presence of chlamydial local IgA antibodies and the
      detection of C. trachomatis. The discrepancies in positive results found between
      some techniques for the detection of C. trachomatis in urethral and semen
      specimens might be explained by variations in the sensitivities and specificities
      of the tests carried out and the use of specimens from different anatomical
      locations. Our findings suggest that C. trachomatis seems to be widespread among
      the male partners of infertile couples in Tunisia. The detection of C.
      trachomatis in urethral or semen specimens can serve as a marker for the presence
      of this organism in the genital tract, which is not necessarily the cause of male
      infertility. The study of the correlation between the detection of chlamydial
      infection markers and the parameters of male fertility seems to be necessary in
      order to determine the direct link between chlamydial infection and male
      infertility and to choose the most efficient technique and most suitable specimen
      with which to diagnose C. trachomatis-associated male infertility.

PMID- 11334472
TI  - Knowledge of emergency contraception among pharmacists and doctors in Durban,
      South Africa.
AB  - OBJECTIVE: To determine the level of knowledge of emergency contraception among
      private-sector pharmacists and doctors. METHOD: This hand-delivered, confidential
      questionnaire survey was undertaken in North and South Central Durban, Kwazulu
      Natal, South Africa. The main outcome measures were frequency of demand for
      emergency contraception and knowledge of its dosing schedule, side-effects and
      contraindications. RESULTS: Ninety-six per cent of pharmacists and 93% of doctors
      had received requests for emergency contraceptive pills within the past year.
      Thirty-two per cent of pharmacists and 28% of doctors prescribed the Yuzpe
      regimen correctly. Only 23 (27%) doctors and 25 (22%) pharmacists were able to
      identify three common side-effects associated with emergency contraceptive pills.
      Forty-six per cent of pharmacists and 49% of doctors correctly indicated that
      there are no absolute contraindications to emergency contraceptive pills other
      than a contraindication to contraceptive pills. Fifty-four per cent of
      pharmacists and 35% of doctors agreed that the multiple use of emergency
      contraceptive pills is risky. CONCLUSION: There is an urgent need to improve the
      knowledge of health-care workers regarding emergency contraception, which forms
      an important back-up method when existing contraception fails or is not used.

PMID- 11334473
TI  - Practices of prescribing oral contraceptives in Poland.
AB  - We developed and performed a survey on practices of prescribing oral
      contraceptives in Poland. The survey was carried out in Warsaw, the capital city
      of Poland and one of the most important areas of the country (approximately 4
      million inhabitants). The main aim of the study was to recognize the rationale
      and practices of prescribing oral contraceptives by gynecologists in Poland (oral
      contraceptives are prescribed mostly by gynecologists, not by general
      practitioners or midwives). The questions were sent to all members of Warsaw's
      Association of Gynecologists, but we have received back only 276 answers (79% of
      the total number of members) and the responses are presented here. The responses
      revealed that the most popular oral contraceptives are those modern formulations
      combining low doses of ethinylestradiol and progestogens such as norgestimate,
      desogestrel, gestodene and levonorgestrel. For gynecologists, the most important
      factors in the selection of an oral contraceptive were the dose of hormones
      (20.3%), the formulation (18.5%), tolerance by patients (23.5%) and past clinical
      experience with the formulation (9.4%). The price was most important for 3.7%,
      and good marketing practices were most important for 8.3% of the gynecologists.

PMID- 11334474
TI  - Experience of the first pelvic examination.
AB  - OBJECTIVES: To analyze women's experiences of the first pelvic examination and
      identify positive and negative components. To learn lessons, and build on and
      incorporate the positive components into a model of good clinical practice.
      METHOD: The open, cross-sectional study was carried out in community family
      planning and young persons clinics. A self-administered questionnaire was offered
      to all women under 25 years of age who attended a family planning or young
      persons clinic during the study period. The questionnaire was constructed to
      determine how experience compared with expectations and which components showed a
      significant trend towards a positive or negative effect. It also aimed to find
      what women considered to be important aspects of an internal examination.
      RESULTS: A total of 167 evaluable questionnaires were completed in which
      experience of the first pelvic examination was reported from family planning
      clinics (41%), general practice (39%) and hospital/genitourinary medicine
      faculties (20%). These first pelvic examinations occurred at a mean age of 17.3
      years (range 11-23 years). Significant trends of a positive experience were found
      when the examination was conducted by a female doctor (p = 0.02), when it was
      conducted in a family planning clinic as opposed to general practice (p = 0.04),
      after permission was sought (p = 0.001) and with increasing age at first
      examination (Mann-Whitney, p = 0.003). There were no significant differences in
      outcome with offer of, or presence of, a chaperone. CONCLUSIONS: A friendly,
      female doctor who seeks permission before the examination, which should be
      uninterrupted, were considered to be important aspects for an internal
      examination.

PMID- 11334475
TI  - Misoprostol for abortion at 9-12 weeks' gestation in adolescents.
AB  - The objectives of the present clinical study were to evaluate the safety and
      efficacy of misoprostol (Cytotec), self-administered into the vagina for medical
      abortion, in adolescents under 18 years ofage. A group of 150 adolescents with
      gestations between 63 and 84 days, with previous written consent from the patient
      and parents or guardians, received 800 microg of vaginal misoprostol every 24 h,
      up to a maximum of three main doses, for abortion. Outcomes assessed included
      successful abortion (complete abortion without surgery), side-effects, decrease
      in hemoglobin, mean time of vaginal bleeding, mean expulsion time and mean time
      for the return of menses. Complete abortion occurred in 126/150 (84.0%, 95%
      confidence interval 77-89) patients. The frequencies of nausea and vomiting were
      statistically significantly higher when compared to those obtained for adult
      females. Vaginal bleeding lasted for 13.2 +/- 3.8 days (median 13 days, range 1
      22 days). The mean expulsion time was 8.0 +/- 3.4 h (median 8 h, range 1-14 h)
      for all subjects who aborted after the first misoprostol dose. The mean drop in
      hemoglobin was statistically significant (p = 0.001), but without clinical
      relevance. From the high abortion rate obtained, we concluded that misoprostol
      alone is a valid method for terminating unwanted pregnancies at 10-13 weeks'
      gestation in adolescents under 18 years of age in the absence of mifepristone.

PMID- 11334477
TI  - A two-stage increase in the dose of misoprostol improves the efficacy of medical
      abortion with mifepristone and prostaglandins.

PMID- 11334476
TI  - Comparison of the effect on acne with a combiphasic desogestrel-containing oral
      contraceptive and a preparation containing cyproterone acetate.
AB  - OBJECTIVE: To investigate the effect of a combiphasic oral contraceptive
      containing ethinylestradiol and desogestrel (combiphasic EE/DSG) on acne,
      compared with a preparation containing ethinylestradiol and cyproterone acetate
      (EE35/CPA). METHODS: An open, randomized, group-comparative, multicenter study
      was carried out, with 172 women randomized to treatment with either combiphasic
      EE/DSG (25 microg desogestrel and 40 microg ethinylestradiol for 7 days followed
      by 125 microg desogestrel and 30 microg ethinylestradiol for 15 days) or EE35/CPA
      (2.0 mg cyproterone acetate and 35 microg ethinylestradiol for 21 days).
      Assessments were performed at pretreatment and after cycles 3 and 6. RESULTS: The
      number of comedones, papules, pustules and nodules significantly decreased in
      both groups over the 6-month study. Compared with pretreatment (= 100%), the
      relative numbers of comedones, papules, pustules and nodules at cycle 6
      significantly decreased to 37%, 38%, 19% and 12.5% in the combiphasic EE/DSG
      group and to 24%, 36%, 17% and 1% in the EE35/CPA group, respectively. All
      reductions were statistically significant (p < or = 0.003) at both cycles 3 and
      6, except for nodules at cycle 6 with combiphasic EE/DSG, which probably resulted
      from differences between the treatment groups at baseline. There were no
      statistically significant differences between the two treatments. In both groups,
      the majority of women with severe acne shifted to a less severe acne category.
      CONCLUSIONS: Combiphasic EE/DSG progressively reduced the number and severity of
      acne lesions during the six cycles of treatment. The reduction in acne with the
      combiphasic oral contraceptive was comparable to a preparation containing the
      antiandrogen cyproterone acetate.

PMID- 11334478
TI  - Diagnostic suspicion and referral bias in studies of venous thromboembolism and
      oral contraceptive use.

PMID- 11334479
TI  - Preferential prescribing of type of combined oral contraceptive pill by general
      practitioners to teenagers with acne.
AB  - OBJECTIVES: To determine the oral contraceptive prescribing patterns of general
      practitioners for teenagers in the UK and any preferential prescribing for those
      with acne. METHOD: The General Practice Research Database was used in a
      retrospective observational study. Records of females aged 13-19 years were
      examined for the years 1994 and 1997. RESULTS: In 1994, third-generation pills
      were widely prescribed, whereas, in 1997, levonorgestrel pills were most commonly
      prescribed. In those with a recent history of acne, the most commonly prescribed
      single product was one containing cyproterone acetate. CONCLUSION: General
      practitioners appear to favor cyproterone acetate-containing pills for those with
      acne; this proclivity became more pronounced after the pill scare. General
      practitioners had all but ceased using third-generation pills in 1997, even when
      there was a therapeutic indication.

PMID- 11334481
TI  - From infection to autoimmunity.
AB  - We have investigated two models of virally-induced autoimmune myocarditis in mice
      using widely different infectious agents. Infection of susceptible BALB/c mice
      with either Coxsackievirus or murine cytomegalovirus results in the development
      of acute myocarditis from day 7-14 after infection, and chronic myocarditis from
      day 28 onwards. The chronic phase of myocarditis is associated with mononuclear
      infiltration of the myocardium and the production of autoantibodies to cardiac
      myosin, although infectious virus cannot be detected past day 14 of infection. T
      cells and autoantibodies have been shown to be important for the development of
      autoimmune myocarditis. Many researchers have investigated the role of molecular
      mimicry in the development of myocarditis after viral infection. This review
      explores the 'adjuvant' effect of infection on the innate immune response and how
      this determines the progression to autoimmune disease. We show that NK cells
      protect against the development of disease, while complement and complement
      receptors are involved in the development of autoimmune myocarditis induced by
      inoculation with virus or cardiac myosin, respectively. Our results suggest that
      the innate immune response to viral and self-antigens may determine whether
      susceptible strains of mice progress to chronic autoimmune disease. These
      findings have broad implications for understanding the role of infection in
      inducing autoimmune disease.

PMID- 11334482
TI  - Molecular mimicry and antigen-specific T cell responses in multiple sclerosis and
      chronic CNS Lyme disease.
AB  - The concept of molecular mimicry provides and elegant framework as to how cross
      reactivity between antigens from a foreign agent with self proteins may trigger
      autoimmune diseases. While it was previously thought that sequence and structural
      homology between foreign and self proteins or the sharing of T cell receptor
      (TCR) and MHC-binding motifs are required for molecular mimicry to occur, we have
      shown that even completely unrelated peptide sequences may lead to cross
      recognition by T cells. The use of synthetic combinatorial peptide libraries in
      the positional scanning format (PS-SCL) together with novel biometric prediction
      approaches has allowed us to describe the recognition profiles of individual
      autoreactive T cell clones (TCC) with unprecedented accuracy. Through studies of
      myelin-specific TCC as well as clones from the nervous system of patients
      suffering from chronic central nervous (CNS) Lyme disease it has become clear
      that at least some T cells are more degenerate than previously anticipated. These
      data will not only help us to redefine what constitutes specific T cell
      recognition, but also allow us to study in more detail the biological role of
      molecular mimicry. A recent clinical trial with an altered peptide ligand (APL)
      of one of the candidate myelin basic protein (MBP) epitopes in MS (amino acids 83
      99) has shown that such a modified MBP peptide may not only have therapeutic
      efficacy, but also bears the potential to exacerbate disease. Thus, we provide
      firm evidence that the basic principles of cross-recognition and their
      pathogenetic significance are relevant in MS.

PMID- 11334483
TI  - Tolerance induction with agonist peptides recognized by autoaggressive
      lymphocytes is transient: therapeutic potential for type 1 diabetes is limited
      and depends on time-point of administration, choice of epitope and adjuvant.
AB  - Immunization with agonist peptides recognized by autoaggressive lymphocytes has
      been used successfully in several animal models for type 1 diabetes (T1D) or
      multiple sclerosis (MS) to prevent disease. Depending on the timing of
      immunization, use of adjuvant and route of administration either elimination of
      autoaggressive T cells or induction of regulation reflected by cytokine shifts
      were described. Since it was also reported that such agonist peptides could
      enhance autoimmunity by activating aggressive lymphocytes, our goal was to re
      evaluate their efficacy in an antigen-specific model of virally-induced T1D that
      allowed us to precisely track the autoaggressive response. We find that rather
      than the route of administration (oral versus sc) the precise timing is important
      for inducing tolerance to self-antigens. Tolerance is transient and only
      immunization during a susceptible phase 10 to 20 days prior to the induction of
      disease but not in prediabetic mice resulted in protection. Further, use of a
      stronger adjuvant (CFA) compared to IFA enhanced the protective effect.
      Mechanistically, a transient loss of autoaggressive T cells was responsible for
      preventing disease, the effect was quantitative and no regulatory lymphocytes or
      cytokine shifts were induced by any of our treatments. Thus, MHC class I
      restricted agonist peptides might only find a limited use in treating autoimmune
      disorders, because tolerance induction is transient and treatment has to be given
      very early, ideally prior to activation of the aggressive response.

PMID- 11334484
TI  - Self-reactive T cells and degeneracy of T cell recognition: evolving concepts
      from sequence homology to shape mimicry and TCR flexibility.

PMID- 11334485
TI  - Requirements for viral-mediated autoimmune diabetes: beta-cell damage and immune
      infiltration.
AB  - The induction of autoimmunity by viruses has been attributed to numerous
      mechanisms. Coxsackievirus B4 (CB4) induces insulin-dependent diabetes mellitus
      (IDDM) in mice resembling the final step of disease progression in humans.
      Following viral infection, autoreactive lymphocytes are activated through
      exposure to damaged islets consequently precipitating IDDM. However, the viral
      and host requirements leading up to this final step have yet to be elucidated. We
      provide evidence that disease induction requires a pre-existing accumulation of
      beta-cell specific autoreactive T cells within the pancreas, as well as the
      infection of islet beta-cells. Therefore, the primary role of CB4 in the
      development of IDDM is to infect tissue, resulting in the presentation of
      sequestered islet antigen, the stimulation of preexisting autoreactive T cells,
      and the initiation of disease.

PMID- 11334486
TI  - Multiple pathways to induction of virus-induced autoimmune demyelination: lessons
      from Theiler's virus infection.
AB  - Infection of SJL mice with wild-type BeAn strain of Theiler's murine
      encephalomyelitis virus (TMEV) leads to CD4(+)T cell-mediated CNS demyelination
      characterized by the development of anti-myelin epitope autoimmune responses via
      epitope spreading during the chronic stage of disease. To exmine the feasibility
      of virus-encoded mimic epitopes to initiate CNS autoimmunity, we recently
      developed a molecular mimicry model of virus-induced demyelinating disease
      wherein a non-pathogenic variant strain of TMEV was engineered to encode a 30-mer
      peptide encompassing the immunodominant myelin proteolipid protein, PLP139-151,
      epitope. SJL mice infected intracerebrally with TMEV encoding either the native
      PLP139-151 determinant or various peptide mimics of the epitope develop an early
      onset demyelinating disease mediated by activated PLP139-151-specific Th1 cells.
      The autoimmune nature of this early-onset demyelinating disease is shown by the
      fact that induction of tolerance to the PLP139-151 peptide prevents clinical
      disease and associated PLP139-151-specific T cell responses without affecting T
      cell reactivity to virus epitopes. Most significantly, TMEV encoding a molecular
      mimic peptide derived from the Haemophilus influenzae bacteria, homologous at
      only six out of thirteen of the core amino acids, led to CNS disease. These
      studies provide conclusive evidence that virus-induced myelin-specific
      autoreactive T cells can be induced by molecular mimicry and provide a useful
      model to study the disease inducing ability of viruses encoding human-disease
      related mimicry peptides.

PMID- 11334487
TI  - Can virus infections trigger autoimmune disease?

PMID- 11334488
TI  - Bcg and autoimmunity: another two-edged sword.
AB  - BCG immunotherapy for bladder carcinoma has been a long-standing treatment
      modality that has proved itself efficient and safe. Most of the side-effects of
      this treatment are minor and of short duration. There have been, nevertheless,
      several reports regarding more severe and long-term complications of BCG therapy
      namely inflammatory arthritis, and occasionally systemic autoimmune
      manifestations. Here, we present four cases of patients who received intravesical
      instillation with BCG for bladder carcinoma and developed long-standing
      inflammatory arthritis. One of these patients developed Reiter's syndrome. We
      also refer to the possible immune mechanisms by which BCG can trigger arthritis,
      as well as to the link between mycobacterial infection, BCG immunotherapy and
      autoimmunity.

PMID- 11334489
TI  - Molecular mimicry in Campylobacter jejuni and Helicobacter pylori
      lipopolysaccharides: contribution of gastrointestinal infections to autoimmunity.
AB  - Molecular mimicry of host structures by the saccharide portion of
      lipopolysaccharides (LPS) of the gastrointestinal pathogens Campylobacter jejuni
      and Helicobacter pylori is thought to be associated with the development of
      autoimmune sequelae. C. jejuni, a leading cause of gastroenteritis, is the most
      common antecedent infection in Guillain-Barre syndrome (GBS), an inflammatory
      neuropathy. Chemical analyses of the core oligosaccharides of neuropathy
      associated C. jejuni strains have revealed structural homology with human
      gangliosides. Serum antibodies against gangliosides are found in one third of GBS
      patients but are generally absent in enteritis cases. Collective data suggest
      that the antibodies are induced by antecedent infection with C. jejuni, and
      subsequently react with nerve tissue causing damage. The O-chains of most H.
      pylori strains express Lewis blood group antigens which are thought to have a
      role in camouflage of the bacterium as these antigens are also present on human
      gastric epithelial cells. In chronic H. pylori infections, bacterial expression
      of Lewis antigens is suggested to be involved in the induction of autoantibodies
      against the Lewis antigen-expressing gastric proton pump. Many aspects of the
      autoimmune mechanisms in C. jejuni -associated GBS and H. pylori -induced
      atrophic gastritis remain unclear, such as the involvement of T cells and the
      role of host factors.

PMID- 11334490
TI  - The mimicry of human glycolipids and glycosphingolipids by the
      lipooligosaccharides of pathogenic neisseria and haemophilus.
AB  - It has been known for many years that bacteria can induce autoimmune responses in
      humans resulting in serious disease. Recent work has shown that a number of
      bacteria that colonize human mucosal surfaces exclusively express antigens on
      their surfaces which are molecular mimics of glycosphingolipids found on human
      cells. These structures are important in the pathogenesis of Neisseria and
      Haemophilus species for both immune evasion and in the adherence and invasion of
      human cells. There is no evidence that colonization or infections by these
      bacterial species is associated with autoimmune disease.

PMID- 11334491
TI  - Autoimmune mechanisms in antibiotic treatment-resistant lyme arthritis.
AB  - In about 10% of patients with Lyme arthritis in the United States, joint
      inflammation persists for months or even several years after the apparent
      eradication of the spirochete, Borrelia burgdorferi, from the joint with
      antibiotic treatment. We propose a model of molecular mimicry affecting
      genetically susceptible individuals to explain this treatment-resistant course.
      The majority of patients with treatment-resistant Lyme arthritis have HLA
      DRB1*0401 or related alleles, and the severity and duration of their arthritis
      correlate with cellular and humoral immune responses to outer-surface protein A
      OspA) of the spirochete. Using an algorithm, the immunodominant epitope of OspA
      presented by the DRB1*0401 molecule was predicted to be located at aa 165-173. In
      a search of the Genetics Computer Group gene bank, only one human protein was
      identified, lymphocyte function associated antigen-1 (hLFA-1), that had sequence
      homology with OspA(165-173)and predicted binding in the DRB1*0401 molecule.
      Synovial fluid T cells from most patients with treatment-resistant arthritis
      responded to both OspA and hLFA-1, whereas those from patients with other forms
      of chronic inflammatory arthritis did not. Molecular mimicry between a dominant T
      cell epitope of OspA and hLFA-1 may be an important factor in the persistence of
      joint inflammation in genetically susceptible patients with treatment-resistant
      Lyme arthritis.

PMID- 11334492
TI  - Polyarteritis nodosa and extrahepatic manifestations of HBV infection: the case
      against autoimmune intervention in pathogenesis.
AB  - Numerous extrahepatic manifestations have been reported in patients with both
      acute and chronic hepatitis B (arthralgias or arthritis, skin rashes,
      glomerulonephritis and neuritis), all of which are present in polyarteritis
      nodosa (PAN) which is the most unique and spectacular extrahepatic manifestation.
      In the 1970s, the frequency of PAN due to the hepatitis B (HBV) reached 30%.
      Immunization programs explain the decrease and it is now down to 7%. PAN usually
      occurs within 6 months of infection. Clinical manifestations reflect this most
      classic form of PAN, Hepatic manifestations including, ALT/AST elevations are
      mild and usually overlooked. Besides HBV, other viruses may be responsible for
      cases of vasculitides including PAN, HIV, Parvovirus B19, and EBV. Different
      pathogenic mechanisms have been identified but immune complexes are mainly
      thought to be responsible. In glomerulonephritis, detailed immunostaining and
      ultrastructural findings indicate that HBe antigen (Ag) is more likely to be the
      responsible antigen. In PAN, fewer reports are available and early studies with
      poorly defined antibodies need to be revisited. Interestingly almost all cases of
      HBV/PAN are associated with wild-type HBV infection, characterised by HBe
      antigenemia and high HBV replication, supporting the concept that lesions could
      result from the deposit of viral Ag/Ab complexes soluble in Ag excess, possibly
      involving HBe Ag. The recent observation of PAN cases associated with precore
      mutation which abrogates the formation of HBe Ag challenges this view. It may
      suggest that other, still undefined, circulating HBV-related Ag(s) distinct from
      HBe Ag could be involved. Remarkably, none of the HBV/PAN cases or
      glomerulonephritis exhibit antineutrophil cycoplasmic antibodies (ANCA)
      reactivity. Viral PAN can now be completely separated from other form of
      vasculitis mostly autoimmune in nature. Based on the efficacy of antiviral agents
      in chronic hepatitis B and of plasma exchanges in PAN we combined both therapies
      to treat HBV PAN. This was associated with swift recovery, even in the most
      severe forms. The perfect time correlation between inhibition of virus
      replication and resolution of all bioclinical signs suggest a direct pathogenic
      role of the virus possibly via immune complexes. Traditional immunosuppressive
      and steroid therapy should no longer be used for HBV PAN cases.

PMID- 11334493
TI  - Hepatitis C and D, retroviruses and autoimmune manifestations.
AB  - Chronic infections with hepatitis C virus (HCV) are associated with various
      autoimmune manifestations, i.e. mixed cryoglobulinemia, membranoproliferative
      glomerulonephritis, autoimmune thyroid diseases, sporadic porphyria cutanea tarda
      and B cell lymphoma. Since exacerbation of hepatitis occurs in 5-10% of HCV
      patients receiving interferon-alpha treatment and may be successfully treated by
      immunosuppression afterwards, hepatitis C was also suspected to be associated
      with autoimmune hepatitis. LKM3 autoantibodies in chronic hepatitis D virus (HDV)
      infection and epitope recognition are discussed. Lately, endogenous and exogenous
      retroviruses have been investigated for the induction of autoimmune diseases.
      Human A type retroviral particles (HIAP), reverse transcriptase activity and anti
      HIAP autoantibodies were detected in patients with Sjogren's syndrome. Anti-HIAP
      and anti-HIV p24 autoantibodies are seen in systemic lupus erythematosus, primary
      biliary cirrhosis and multiple sclerosis. Multiple sclerosis was even associated
      with a new human retrovirus called multiple sclerosis associated retrovirus
      (MSRV). In diabetes long terminal repeats (LTR) were detected in the HLA DQB1
      locus, which was shown to associate with an increased risk of diabetes. A second
      retrovirus called IDDMK(1,2)22 was reported to code for a superantigen, which was
      implicated as a potential cause of diabetes. This hypothesis, however, was
      challenged repeatedly. Until now it is unknown whether endogenous retroviruses
      are aetiological agents of autoimmune diseases or an epiphenomenon, induced by
      coinfecting viruses (e.g. herpes viruses) and inflammatory processes.

PMID- 11334494
TI  - AIDS: an immune response against the immune system. Role of a precise
      tridimensional molecular mimicry.
AB  - This study describes some of the expected autoimmune consequences of a recently
      described virus-host molecular mimicry in patients infected with human
      immunodeficiency virus (HIV). Some physical and structural analogies have been
      recently identified between some precise antigenic sites of the trimeric
      ectodomain of the transmembrane envelope protein of AIDS-associated lentiviruses
      (HIV, Simian immunodeficiency virus and feline immunodeficiency virus) and some
      precise and crucial interleukin 2 (IL-2) antigenic sites of the corresponding
      infected species (man, monkey, cat). As expected, HIV-positive sera recognize
      human IL-2, and a cross-reactivity was found between the structurally and
      physically analogous antigenic sites of GP41 (HIV1) and human IL-2. The possible
      impact on AIDS-associated disorders of this tridimensional GP41 (HIV1)/human IL-2
      molecular mimicry is suggested.

PMID- 11334496
TI  - Antigen-presenting cell activation: a link between infection and autoimmunity?
AB  - The onset of autoimmune diseases such as type I diabetes and multiple sclerosis
      is often thought to be associated with infection. This has led to studies of
      molecular mimicry between infectious agents and the self-antigens associated with
      autoimmunity. Despite many claims, however, a single causative infectious agent
      for autoimmunity has not been found. An alternative possibility is that many
      infectious agents are capable of non-specifically enhancing the likelihood of an
      autoimmune attack. Here we show how infectious agents may activate antigen
      presenting cells leading to the activation of autoreactive T cells by otherwise
      innocuous antigens. The mechanism of activation involves upregulation of co
      stimulatory molecules on the antigen-presenting cell resulting in a lowering of
      the threshold required for activation. These results help explain how diverse
      infectious agents could cause autoimmune disease in susceptible individuals.

PMID- 11334495
TI  - Structural basis of molecular mimicry.
AB  - Infectious agents are thought to play an important role in the development of
      autoimmune diseases. Sequence similarity between infectious agents and self
      proteins (molecular mimicry) has been proposed as a mechanism for the induction
      of autoimmunity [1]. However, it has been difficult to identify microbial
      peptides that activate autoreactive T cells using conventional sequence
      alignments. This chapter reviews progress made in the identification of such
      microbial peptides based on the analysis of structural features that are
      important for TCR recognition of MHC-bound peptides [2].

PMID- 11334497
TI  - Epidemiology of autoimmune reactions induced by vaccination.
AB  - In order for vaccinations to 'work', the immune system must be stimulated. The
      concern that immunizations may lead to the development of autoimmune disease
      (AID) has been questioned. Since AID occur in the absence of immunizations, it is
      unlikely that immunizations are a major cause of AID. Epidemiological studies are
      needed, however, to assess whether immunizations may increase the risk in some
      susceptible individuals. This paper discusses the evidence for and against
      vaccination as a risk factor for AID. Evidence for immunizations leading to AID
      come from several sources including animal studies, single and multiple case
      reports, and ecologic association. However more rigorous investigation has failed
      to confirm most of the allegations. Unfortunately the question remains difficult
      to address because for most AIDs, there is limited knowledge of the etiology,
      background incidence and other risk factors for their development. This
      information is necessary, in the absence of experimental evidence derived from
      controlled studies, for any sort of adequate causality assessment using the
      limited data that are available. Several illustrative examples are discussed to
      highlight what is known and what remains to be explored, and the type of
      epidemiological evidence that would be required to better address the issues.
      Examples include the possible association of immunization and multiple sclerosis
      (and other demyelinating diseases), type 1 diabetes mellitus, Guillain-Barre
      Syndrome, idiopathic thrombocytopenic purpura, and rheumatoid arthritis.

PMID- 11334498
TI  - Induction of autoimmunity through bystander effects. Lessons from immunological
      disorders induced by heavy metals.
AB  - Autoreactive T cells exist in healthy individuals and represent a potential
      reservoir of pathogenic effectors which, when stimulated by microbial adjuvants,
      could trigger an autoimmune disease. Experimental studies have indicated that
      xenobiotics, well defined from a chemical point of view, could promote the
      differentiation of autoreactive T cells towards a pathogenic pathway. It is
      therefore theoretically possible that compounds present in vaccines such as
      thiomersal or aluminium hydroxyde can trigger autoimmune reactions through
      bystander effects. Mercury and gold in rodents can induce immunological disorders
      with autoimmune reactions. In vitro, both activate signal transduction pathways
      that result in the expression of cytokines, particularly of IL-4 and IFNgamma. In
      a suitable microenvironment heavy metals could therefore favour the activation of
      autoreactive T cells. In that respect, genetic background is of major importance.
      Genome-wide searches in the rat have shown that overlapping chromosomal regions
      control the immunological disorders induced by gold salt treatment, the
      development of experimental autoimmune encephalomyelitis and the
      CD45RC(high)/CD45RC(low)CD4(+)T cells balance. The identification and functional
      characterization of genes controlling these phenotypes may shed light on key
      regulatory mechanisms of immune responses. This should help to improve efficacy
      and safety of vaccines.

PMID- 11334499
TI  - From autoimmune responses to autoimmune disease: what is needed?

PMID- 11334500
TI  - Modelling the effects of genetic and environmental factors on the risk of
      autoimmune disease.
AB  - The presence or absence of autoimmune disease is a qualitative outcome resulting
      from the combined influences of genetic, environmental and stochastic factors
      that interact in complex ways. Because of the nature of these interactions, the
      effects of risk factors that contribute to the aetiology of disease cannot be
      adequately assessed individually. Here, I propose an approach to multiparameter
      modelling of autoimmune disease that incorporates Falconer's concept of liability
      in a generalized linear model. Specifically, a logistic model, allied to that
      used to assess the influence of genetic risk factors, is suggested. The limits of
      modelling autoimmune disease and the requirements for data collection are also
      briefly discussed.

PMID- 11334501
TI  - Antigenic mimicry, clonal selection and autoimmunity.
AB  - The triggering of autoimmunity by infection or immunization is often blamed on
      antigenic mimicry. But the concept of antigen mimicry impinges on our
      understanding of adaptive immunity in general, and not only on autoimmunity. Here
      are some thoughts about the consequences of immune mimicry.

PMID- 11334502
TI  - On the relationship between viral infection and autoimmunity.

PMID- 11334503
TI  - Protective role of infections and vaccinations on autoimmune diseases.
AB  - Infectious agents may induce autoimmune disease through several mechanisms,
      notably antigen mimicry and inflammation of the target organ; conversely,
      infections may protect from autoimmune diseases. This paradoxical effect has been
      demonstrated for a number of bacteria, viruses and parasites on a variety of
      spontaneous or experimentally induced animal models of autoimmune diseases (e.g.
      experimental allergic encephalomyelitis, lupus mice, non-obese diabetic mice).
      The mechanisms of the protection are still ill-defined, and probably vary
      according to models. Stimulation of immunoregulatory CD4 T cells has been shown
      to play a central role in several major models. The role of superantigens is also
      important, like that of Toll-like receptors. Antigen competition is another major
      mechanism, itself open to several interpretations. Epidemiological data support a
      protective role of infections on human allergic and autoimmune diseases. These
      diseases are much more common in countries with high socio-economic development
      (typically Northern countries in Europe). The reason for this cannot be fully
      explained by genetic differences because migrating populations develop these
      diseases with the same incidence of the adoptive country rather than that of the
      country of origin. It is interesting that the frequency of these diseases has
      been increasing in developed countries over the last 20 years but not in
      undeveloped ones.

PMID- 11334504
TI  - Type 1A diabetes induced by infection and immunization.
AB  - Type 1A diabetes is an immune mediated disorder that results from progressive
      destruction of the islet beta-cells in the setting of genetic susceptibility.
      Both MHC and non-MHC genes contribute to disease with class II HLA molecules
      major determinants of susceptibility or protection. The presence of multiple anti
      islet autoantibodies is associated with a high risk of disease progression, and
      the first anti-islet autoantibodies may appear as early as the first year of
      life. Congenital rubella is the only infection clearly associated with the
      development of type 1A diabetes. With the ability to detect children in the first
      year of life activating autoimmunity, prospective studies may in the future
      document additional environmental factors either increasing or decreasing
      diabetes risk.

PMID- 11334505
TI  - Heart-directed autoimmunity: the case of rheumatic fever.
AB  - Molecular mimicry was proposed as a potential mechanism for streptococcal
      sequelae leading to rheumatic fever (RF) and rheumatic heart disease (RHD).
      CD4(+)infiltrating T cells are able to recognize streptococcal M peptides and
      heart tissue proteins. We analyzed the M5 peptide- and heart-specific responses,
      cytokine profile and T cell receptor (TCR) BV usage from peripheral and heart
      infiltrating T cell lines and clones from patients across the clinical spectrum
      of ARF/RHD. The patient with ARF displayed a higher frequency of mitral valve
      infiltrating T cell clones reactive against M5: 1-25, 81-103 and 163-177 regions
      and several valve-derived proteins than the post-RF and chronic RHD patient (67%;
      20% and 27%, respectively). The presence of oligoclonal BV families indicative of
      oligoclonal T cell expansion among mitral valve-derived T cell lines was
      increased in the chronic RHD patient. Furthermore, mitral valve T cell lines from
      all patients produced significant amounts of inflammatory cytokines interferon
      gamma (IFN-gamma) and tumour necrosis factor-alpha (TNFalpha) in response to
      M5(81-96) peptide, with the highest production attained by the chronic RHD
      patient. These data are consistent with an important role for M5 peptide and host
      antigen-driven, T1-type CD4(+)T cells in the pathogenesis of RHD and heart lesion
      progression after recurrence of the streptococcal infection.

PMID- 11334506
TI  - From reactive arthritis to rheumatoid arthritis.
AB  - Reactive arthritis was initially described as a sterile synovitis, without
      microbial components present in the joint tissue. It has, however, become evident
      that bacterial degradation products, and even bacterial DNA, are present in the
      synovium of patients with this disease. Since intestinal pathogens are important
      causes of reactive arthritis, and since cellular homing allows transport of
      bacterial products from the gut to synovium, we have approached the etiology of
      rheumatoid arthritis from this point of view. A series of observations has led to
      a hypothesis that patients with rheumatoid arthritis might favour, for genetic
      reasons, intestinal bacteria which are capable of inducing arthritis. In the long
      run, with continuous seeding of bacterial products from the gut, the synovial
      inflammation is followed by erosion, exposition of cartilage antigens, and
      autoimmunity.

PMID- 11334507
TI  - Chemical Interaction between Nonionic Surfactants and an Acid Dye.
AB  - Complexation of the dye Direct Red 1 with a series of laurylamine surfactants
      with varying number of ethylene oxide units has been studied by voltammetry. From
      the measurement of the cathodic current of both dye and surfactant, the stability
      constants of the established equilibrium between the dye D, the surfactant S, and
      the dye-surfactant complex D-S can be calculated. The values of the stability
      constant K at 25 degrees C calculated for a defined dye-surfactant stoichiometry
      depend on the number of ethylene oxide units incorporated by the surfactant.
      These constants decrease by one order of magnitude at 60 degrees C maintaining
      the dependence on the number of ethylene oxide units. Copyright 2001 Academic
      Press. 

PMID- 11334508
TI  - An Enthalpic Analysis on the Aggregation of Colloidal Particles Studied by
      Microcalorimetry.
AB  - There are different theories concerning the stability of colloidal suspensions.
      Most of them arise from the well-known DLVO theory which relates colloidal
      stability to intermolecular forces between particles. Experimental corroboration
      of these theories has been obtained mainly by using different optical techniques
      that analyze changes in the optical properties of the solution while particles
      aggregate. However, no attention has been paid to studying the aggregation
      process thermodynamically. This is why we have focussed on studying the heat
      released during the agglutination of polystyrene particles. The enthalpy change
      in this aggregation process was detected by using a highly sensitive and modern
      technique called isothermal titration calorimetry. In addition, some results
      about repeptization, that is, reversibility in the aggregation process, are also
      shown. Copyright 2001 Academic Press. 

PMID- 11334509
TI  - Determination of Low Interfacial Tension with a Laser Light Scattering Technique
      and a Comparative Analysis with Drop Shape Methods.
AB  - A comparative analysis of laser light scattering and drop shape techniques for
      measuring low interfacial tension is provided with particular reference to the
      gas condensate systems in petroleum reservoirs. Measurements of interfacial
      tensions for two real reservoir gas condensate samples were undertaken at
      elevated pressure and temperature reservoir conditions with the laser light
      scattering technique. The purposes of this study are (a) to clarify some existing
      confusion on the usefulness of three major interfacial tension measurement
      methods, pendant drop, spinning drop, and laser light scattering; and (b) to show
      the applicability of the laser light scattering technique to real reservoir gas
      condensate interfaces at low interfacial tensions. The laser light scattering
      technique has appeared to be the most suitable approach for the determination of
      low gas condensate interfacial tensions at reservoir conditions in terms of
      precision and operation. Copyright 2001 Academic Press. 

PMID- 11334510
TI  - Synthesis and Characterization of a Novel Addition-Fragmentation Reactive
      Surfactant (TRANSURF) for Use in Free-Radical Emulsion Polymerizations.
AB  - The synthesis and characterization of a new type of chain-transfer-active
      surfactant (i.e., TRANSURF) is reported. The compound was designed on the basis
      of the chemistry of macromers, which undergo free-radical chain-transfer addition
      fragmentation reactions. In effect this allows incorporation of the surfactant
      molecule into the polymer backbone, and thus reduces the influence of surfactant
      migration during film formation. Surfactants of this type, containing two
      hydrophilic head groups, can have a marked influence on the polymer and latex
      properties (e.g., molecular weight distributions and particle size).
      Characterization of the physical properties of this surfactant was therefore
      carried out using surface tension, conductivity, and fluorescence techniques.
      Because of the surfactant's unusual "bolaform" (alpha, omega) (Zana, R., in
      "Structure-Performance Relationships in Surfactants" (K. Esumi and M. Ueno,
      Eds.), Surfactant Science Series 70, Dekker, New York, 1997) structure the
      micelle formation process has been found to be quite different from that of the
      conventional surfactant, sodium dodecyl sulfate (SDS). From the surface tension
      data a flat molecular conformation was evident at 1x10(-3) mol dm(-3) (131 A(2)
      surface area), which we assumed to correspond to the low aggregation number of
      premicellar aggregates. There is evidence to suggest formation of a larger volume
      of the microdomains in these micelles compared to that in SDS. At higher TRANSURF
      concentrations, however, we find no clear indication of a switch to a "wicket"
      type conformation, although such conformational changes cannot be ruled out.
      Copyright 2001 Academic Press. 

PMID- 11334511
TI  - Formation of Small Silica Aggregates by Turbulent Aggregation.
AB  - Aggregation of silica powder in water has been experimentally studied by
      turbidimetry. Aggregation was carried out in a stirred tank under physicochemical
      conditions corresponding to attractive interparticle forces. The effects of
      different primary particle sizes and stirring rates on aggregation dynamics have
      been studied. The scattering cross sections of silica aggregates were calculated
      in the framework of the anomalous diffraction approximation of light scattering
      theory. Aggregation has been studied by using Kusters's and Brakalov's
      approaches. By comparison between experimental and theoretical turbidity changes
      with time it has been shown that aggregates are small and slightly porous. The
      aggregation process is characterized by a weak fractal dimension D(wf) and an
      aggregate limit size L.D(wf) is found in the range 2.4-2.5. D(wf) (respectively
      L) is a weakly increasing (respectively decreasing) function of the stirring rate
      or of the shear rate. Copyright 2001 Academic Press. 

PMID- 11334512
TI  - Chemical Modifications on Human Hair Studied by Means of Contact Angle
      Determination.
AB  - Wetting properties of a solid surface can change as a consequence of chemical
      treatment. There is a relationship between the molecular structure of a surface
      and the macroscopic properties of this surface such as wetting and adhesion.
      Information on the surface energy of a solid was obtained by calculating polar
      and dispersion force contributions by means of contact angle determination. The
      superficial modification undergone by human hair treatments with or without
      hydrogen peroxide at alkaline pH was studied by means of wetting force
      measurements. The wetting increase in treated human hair fibers was analyzed
      following the Huttinger method using contact angle data, taking into account the
      acid-base and dispersion components of the total wetting adhesion work. The
      hydrogen peroxide treatment at alkaline pH leads to a partial removal of
      hydrocarbon chains and to the formation of ionic groups (cysteic acid residues)
      on the outer scale cell surface. The latter phenomenon was observed by means of
      an increase in the acid-base adhesion work versus water wetting liquid at
      alkaline pH. Copyright 2001 Academic Press. 

PMID- 11334513
TI  - Preparation and Characterization of Metal Sulfides in Ethylenediamine under
      Ambient Conditions through a gamma-Irradiation Route.
AB  - The gamma-irradiation technique has been extended to irradiate liquid
      ethylenediamine containing metal ions and sulfur powder, and a series of uniform
      metal sulfide particles including CdS, PbS, Cu(2)S, and Ag(2)S have been prepared
      at room temperature. X-ray powder diffraction, transmission electron microscopy,
      X-ray photoelectron spectroscopy, and UV-visible spectra have been used to
      characterize the products. In addition, the discussion shows that ethylenediamine
      and solvated electrons formed in ethylenediamine play crucial roles during the
      synthetic process. The stability constants of the metal chelates with
      ethylenediamine, the solubility product constants of the metal sulfides, and the
      standard electrode potentials of the metal ions also directly control the
      formation of metal sulfides. Copyright 2001 Academic Press. 

PMID- 11334514
TI  - Atomic Force Microscopy Study of the Adhesion of Saccharomyces cerevisiae.
AB  - An atomic force microscope (AFM) has been used to quantify directly the adhesion
      of metabolically active Saccharomyces cerevisiae cells at a hydrophilic mica
      surface, a mica surface with a hydrophobic coating, and a protein-coated mica
      surface in an aqueous environment. The measurements used "cell probes"
      constructed by immobilizing a single cell at the apex of a tipless AFM
      cantilever. Adhesion was quantified from force-distance data for the retraction
      of the cell from the surface. The data indicated stretching and sequential bond
      breaking as the cell probe was retracted from all of the surfaces. Detailed
      studies were made for physiologically active cells, which were shown to have
      different adhesion properties to glutaraldehyde-treated cells. Greatest cell
      adhesion was measured at the hydrophobic surface. Prior adsorption of a bovine
      serum albumin protein layer at the hydrophilic surface did not significantly
      affect cell adhesion. Changes in yeast surface hydrophobicity and zeta-potential
      with yeast cell age were correlated with differences in adhesion. Cells from the
      stationary phase adhered most strongly to a mica surface. Time of surface contact
      was demonstrated to be important. Both the force needed to detach a cell from a
      hydrophilic mica surface and the length of the adhesive interaction increased
      after 5 min contact. The AFM cell probe technique gives unique insights into
      primary colonization events in biofilm formation. It will continue to aid both
      fundamental studies and the assessment of new procedures that are designed to
      lower cell adhesion at surfaces relevant to biotechnology, medicine, and
      dentistry Copyright 2001 Academic Press. 

PMID- 11334515
TI  - Identification of Skim Milk Electroacidification Fouling: A Microscopic Approach.
AB  - Bipolar membrane electroacidification (BMEA) was used to produce high-purity
      bovine milk casein isolates. However, a deposit suggested to be a mix of calcium
      and magnesium salts was observed on the cation-exchange membrane (CEM) side in
      contact with the base. The aim of the present study was to complete the
      identification of the deposit formed on CMX membrane during bipolar membrane
      electroacidification of skim milk, and to characterize its physical structure at
      the interfaces of CEM. The results showed that a calcium deposit was found on
      both sides of the membranes as well as inside the membrane. This fouling was
      identified as calcium carbonate, but was likely a mix between calcium carbonate
      and hydroxyde. Copyright 2001 Academic Press. 

PMID- 11334516
TI  - Electrophoretic Mobility Study of the Adsorption of Alkyl Xanthate Ions on Galena
      and Sphalerite.
AB  - The adsorption of ethyl and amyl xanthate ions on galena and sphalerite fines has
      been studied using electrophoretic light-scattering (ELS) measurements. It was
      performed on galena and sphalerite (<2&mgr;m) in aqueous solution at different
      potassium ethyl xanthate (PEX) and potassium amyl xanthate (PAX) concentrations.
      It has been observed that the presence of PEX or PAX caused the isoelectric
      points (IEP) of galena and sphalerite fines to shift and the electrophoretic
      mobility to reverse in sign, indicating that the xanthate ions chemisorbed on
      galena and sphalerite surfaces. This adsorption markedly broadened the
      electrophoretic mobility distribution of the mineral fines, suggesting that the
      populations of the particles have quite different adsorption densities of
      xanthate ions, and therefore the particle hydrophobicity was different. This
      phenomenon might be attributable to the effect of the hemimicelle adsorption of
      the xanthate ions on the minerals, the nonuniform distribution of active sites
      and their degree of activity, the effect of particle size and shape, etc. The
      nonuniform adsorption has been found to increase with increasing PEX or PAX
      concentration, reaching a maximum at a medium concentration followed by a
      decline. Also, experimental results have demonstrated that the nonuniform
      adsorption of the xanthate ions is much stronger on sphalerite than on galena,
      which may explain why sphalerite has a worse flotation response than galena when
      alkyl xanthates are used as collectors in flotation systems. Copyright 2001
      Academic Press. 

PMID- 11334517
TI  - Effect of Dodecyl Alcohol on the Potentiometric Response of an Isopropyl Xanthate
      Ion-Selective Electrode.
AB  - An isopropyl xanthate ion-selective electrode was constructed using as a carrier
      the complex trioctylmethylammonium-isopropyl xanthate. Two kinds of plastic
      membranes were built, with dioctyl phthalate (DOA) and dioctyl adipate as
      plasticizers. In both cases, the electrical responses were linear in a wide range
      of xanthate concentrations, with the limit of detection between 10(-4) and 10(-5)
      M. The electrical response was improved by adding only 3 &mgr;mol of dodecyl
      alcohol per membrane. This fact seems to indicate not only that the fluidity is
      relevant but also that the surface polarity of the plastic membrane plays an
      important role. The analysis of some added salts shows that isobutyl xanthate is
      a strong interfering agent for the DOA electrode. Nitrate interferes weakly,
      whereas chloride, acetate, and carbonate do not affect the electrical response of
      both kinds of electrodes. Copyright 2001 Academic Press. 

PMID- 11334519
TI  - Interfacial Characteristics and Fracture Toughness of Electrolytically Ni-Plated
      Carbon Fiber-Reinforced Phenolic Resin Matrix Composites.
AB  - The electrolytic plating of metallic nickel on a carbon fiber surface has been
      carried out in order to improve the interfacial adhesion and the mechanical
      properties in carbon fiber/phenolic matrix composite systems. The surface and the
      mechanical interfacial properties of composites are characterized by X-ray
      photoelectron spectrometry (XPS), surface free energy, and the critical stress
      intensity factor (K(IC)). From the experimental results, it is clearly revealed
      that the oxygen functional groups and the metallic nickel on fibers largely
      affect the mechanical interfacial behavior of the composites, resulting in
      increased surface polarity, whereas the nitrogen functional groups have no
      effect. Also, a good correlation between surface oxygen functional groups and
      mechanical interfacial properties and between wettability and K(IC) is
      established and it is found that a 10 A m(-2) current density is the optimum
      condition for this system. Copyright 2001 Academic Press. 

PMID- 11334518
TI  - Interfacial Aspects of Electrodeposited Conductive Fibers/Epoxy Composites using
      Electro-Micromechanical Technique and Nondestructive Evaluation.
AB  - Interfacial adhesion and nondestructive behavior of the electrodeposited (ED)
      carbon fiber reinforced composites were evaluated using the electro
      micromechanical technique and acoustic emission (AE). Interfacial shear strength
      (IFSS) of the ED carbon fiber/epoxy composites was higher than that of the
      untreated case. This might be expected because of the possible chemical and
      hydrogen bonding based on an electrically adsorbed polymeric interlayer.
      Logarithmic electrical resistivity of the untreated single-carbon fiber composite
      increased suddenly to infinity when the fiber fracture occurred, whereas that of
      the ED composite increased relatively broadly up to infinity. This may be due to
      the retarded fracture time as a result of the enhanced IFSS. In single- and 10
      carbon fiber composites, the number of AE signals coming from the interlayer
      failure of the ED carbon fiber composite was much larger than that of the
      untreated composite. As the number of each first fiber fracture increased in the
      10-carbon fiber composite, the electrical resistivity increased stepwise, and the
      slope of logarithmic electrical resistance increased. In the three-graphite
      filament composite with a narrow 1 time inter-filament distance, the total
      numbers of the filament fracture and the IFSS were smaller than those of the
      wider 5 times case. This might be because the interacting fracture energy caused
      by a filament break could affect the adjacent filaments. Copyright 2001 Academic
      Press. 

PMID- 11334520
TI  - Thermodynamic Analysis of Proteins Adsorbed on Silica Particles: Electrostatic
      Effects.
AB  - Electrostatic effects on protein adsorption were investigated using differential
      scanning calorimetry (DSC) and adsorption isotherms. The thermal denaturation of
      lysozyme, ribonuclease A (RNase), and alpha-lactalbumin in solution and adsorbed
      onto silica nanoparticles was examined at three concentrations of cations: 10 and
      100 mM of sodium and 100 mM of sodium to which 10 mM of calcium was added. The
      parameters investigated were the denaturation enthalpy (DeltaH), the temperature
      at which the denaturation transition was half-completed (T(m)), and the
      temperature range of the denaturation transition. For lysozyme and RNase,
      adsorption isotherms depend strongly on the ionic strength. At low ionic strength
      both proteins have a high affinity for the silica particles and adsorption is
      accompanied by a 15-25% reduction in DeltaH and a 3-6 degrees C decrease in T(m),
      indicating that the adsorbed state of the proteins is destabilized. Also, an
      increase in the width of the denaturation transition is observed, signifying a
      larger conformational heterogeneity of the surface bound proteins. At higher
      ionic strengths, both with and without the addition of calcium, no significant
      adsorption-induced alteration in DeltaH was observed for all three proteins. The
      addition of calcium, however, decreases the width of the denaturation transition
      for lysozyme and RNase in the adsorbed state. Copyright 2001 Academic Press. 

PMID- 11334521
TI  - Desorption of Low-Charge-Density Polyelectrolyte Adlayers in Aqueous Sodium n
      Dodecyl Sulfate Solution.
AB  - The association between low-charge-density polyelectrolytes adsorbed onto
      negatively charged surfaces (mica and silica) and an anionic surfactant, sodium
      dodecyl sulfate (SDS), has been investigated using surface force measurements,
      ellipsometry, and XPS. All three techniques show that the polyelectrolyte desorbs
      when the SDS concentration is high enough. The XPS study indicates that
      desorption starts at a SDS concentration of ca. 0.1 unit of cmc (8x10(-4) M) and
      that the desorption proceeds progressively as the SDS concentration is increased.
      Surface force measurements show that for the polyelectrolyte studied here, having
      1% of the segments charged, the desorption proceeds without any swelling of the
      adsorbed layer. This behavior differs from that observed when polyelectrolytes of
      greater charge density are used. Copyright 2001 Academic Press. 

PMID- 11334522
TI  - Tetrakis(octadecylthio)Tetrathiafulvalene: Influence of Long Alkyl Chains on the
      Architecture and Electrochemical Properties of LB Films.
AB  - We present here a study of a tetrathiafulvalene derivative,
      tetrakis(octadecylthio)tetrathiafulvalene (TTFH), arranged in LB films together
      with a detailed characterization process by means of UV-vis, IR, SEM, and X-ray
      diffraction that has allowed us to propose a packing model. These films were
      exposed to iodine vapor and this doping process was carefully followed using UV
      vis and IR spectroscopy. The redox properties of the TTFH were studied in both
      organic solution and LB films. The results have been interpreted in terms of the
      molecular structure and the LB film architecture. Copyright 2001 Academic Press. 

PMID- 11334524
TI  - Transport of Acids through Polyether-Sulfone Anion-Exchange Membrane.
AB  - Diffusion dialysis of sulfuric acid and hydrochloric acid into water with a
      polyether-sulfone anion-exchange membrane was studied. Transport of sulfuric acid
      and hydrochloric acid through the membrane has been quantified by diffusion
      coefficients and mass transfer coefficients. The mass transfer coefficients were
      investigated as a function of the rotational speed of the stirring rate of both
      sides of the membrane and with different pH ranges. It was observed that the
      diffusion dialysis seems to be dependent on the rotational speed of the stirrer;
      in contrast, the membrane mass transfer coefficients are independent of
      rotational speed, but they are slightly affected by the initial acid
      concentration in donor phase. Copyright 2001 Academic Press. 

PMID- 11334523
TI  - Aqueous Suspensions of Poly(ethylene Glycol)/Pyrocarbon/Fumed Silica.
AB  - Aqueous suspensions of fumed silica and pyrocarbon/silica (CS) in the presence of
      dissolved poly(ethylene glycol) (PEG) were studied using (1)H NMR spectroscopy
      with freezing-out of bulk water and quantum chemical computations of the chemical
      shifts. The freezing effect for PEG/water is akin to that for low-molecular
      organics, as formation of solid phases of water (ice) and PEG occurs, and their
      mixture forms at the eutectic temperature. In the aqueous suspensions of fumed
      silica or CS, PEG molecules are localized at the solid-liquid interfaces and do
      not form the bulk solution even at large concentrations; however, the amount of
      bulk undisturbed water rises due to formation of the immobilized PEG layer. For
      such suspensions of silica or CS at a low amount of pyrocarbon (C(C)=4 wt%),
      there is a portion of the graph of the surface free energy (gamma(S)) increasing
      nearly linearly with the PEG concentration (C(PEG)); however, in the case of
      large C(C)=40 wt% in CS, a similar effect is not observed, as gamma(S) is maximal
      at low C(PEG)=0.1 wt%. Copyright 2001 Academic Press. 

PMID- 11334525
TI  - Preparation of Nanosized Crystalline CdS Particles by the Hydrothermal Treatment.
AB  - We report studies of the effect of hydrothermal treatment on physical properties
      such as crystalline phase, size, and morphology of nanosized cadmium sulfide
      (CdS) particles. CdS precipitates have been synthesized by the reaction of
      Cd(NO(3))(2) with Na(2)S at room temperature. These CdS precipitates have been
      hydrothermally treated in the range 120-240 degrees C with variation of the
      treatment time. The effects of acid catalysts and other additives were also
      investigated. The particles prepared were characterized by XRD, TEM, and BET
      methods. With increased hydrothermal treatment temperature and time,
      crystallization from amorphous to crystalline form, cubic or hexagonal, and an
      increase of particle size occurred. CdS particles of well-developed hexagonal
      form were obtained at a hydrothermal treatment temperature of 240 degrees C; the
      primary hexagonal grain size was on the order of 20-30 nm. The addition of an
      acid catalyst, HCl, or of Cd(NO(3))(2) into the precipitate sol promoted crystal
      growth and phase transformation during the hydrothermal treatment, but another
      additive, Na(2)S, showed the opposite trend. It appears that hydrothermal
      treatment combined with proper additives could be an effective method for
      preparation of nanosize crystalline CdS particles. Copyright 2001 Academic Press.

PMID- 11334526
TI  - Precipitation and Solubility of Calcium Soaps in Basic Aqueous Media.
AB  - Measurements of the surface tension of aqueous media containing calcium salts of
      different fatty acids, whose structure only varied by the number of C=C
      unsaturations along their aliphatic chains, showed that their solubility
      increased as a function of this parameter going from near zero for calcium
      stearate to 4x10(-4) mol l(-1) for the linolenate homologue. The solubility
      product of the calcium soap corresponding to each tested fatty acid was estimated
      by using the anionic fatty acids adsorption isotherms in order to obtain the
      amount of dissolved ionic fatty acid at increasing concentration of calcium ions.
      These findings are discussed in terms of their serious repercussions on the
      operations related to flotation deinking in waste paper recycling. Copyright 2001
      Academic Press. 

PMID- 11334527
TI  - Wettability of Nematic Liquid Crystals.
AB  - Organic liquids such as nematic liquid crystals should wet solids with high
      surface energies like mica, yet they generally do not. In the model proposed
      here, the affinity to wet the solid in form of Hamaker forces is opposed by
      elastic effects due to nematic order. Results predict correctly that such liquids
      show small contact angles and the formation of ultrathin liquid films ahead of
      the bulk drops. Copyright 2001 Academic Press. 

PMID- 11334528
TI  - Zeta Potential of Highly Charged Thin Double-Layer Systems.
AB  - Electrophoretic measurements under d.c. conditions involve a fundamental
      ambiguity for particles with a high zeta potential; two very different values of
      zeta potential can be ascribed to the same mobility. In the case of a polystyrene
      sulfate latex studied previously, selecting the higher (absolute) value gave a
      more consistent picture of the interface and also removed an anomaly in the
      electrokinetic behavior as a function of indifferent electrolyte concentration.
      Confirmation that the higher value is the correct one, however, was still needed.
      The ambiguity is resolved unequivocally here by the use of high-frequency
      mobility measurements using electroacoustics, since the mobility spectra for the
      high and low zeta potentials are very different. The interpretation is supported
      by the dielectric relaxation spectra of this material in the megahertz region.
      Copyright 2001 Academic Press. 

PMID- 11334529
TI  - Effect of Collision Efficiency on the Evolution of the Surface of Diffusion
      Limited Deposits.
AB  - The effect of the collision efficiency of particles deposited onto a rough
      substrate and the evolution of the deposit profile were investigated using 2D on
      lattice Monte Carlo simulations. The case of a diffusive long-range transport
      regime as representative of the colloidal deposition from the suspended phase was
      considered. The initial profile of the substrate was modeled as a sinusoidal
      wave. The decay of the initial profile in the course of deposition was monitored
      by a decrease in the Fourier amplitude A(w) corresponding to the wavelength of
      the initial roughness. The best "memory" of the deposit, i.e., the slowest decay
      of A(w), was found to correspond to intermediate values ( approximately 0.1) of
      the collision efficiency. Copyright 2001 Academic Press. 

PMID- 11334530
TI  - Interactions of Methyl Orange with Cyclodextrin/Sodium-Montmorillonite Systems
      Probed by UV-Visible Spectroscopy.
AB  - Clay mineral colloids play important roles in the adsorption of polar organic
      contaminants in the environment. Similarly, cyclodextrins (CD) can entrap poorly
      water-soluble organic compounds. A combination of CDs and clay minerals affords
      great opportunities to investigate simultaneously complexation and adsorption
      processes involving organic contaminants. In this work, we investigated in situ
      the extent of adsorption and/or complexation of a molecular probe, methyl orange
      (MO), in CD/sodium montmorillonite systems using UV-visible spectroscopy. The
      anion form of MO interacts with the clay surface via cationic bridges, whereas
      the cation form is weakly adsorbed by a cation-exchange mechanism. Further, in
      acidic media, there is a local competition between MO and the montmorillonite
      surface for H(+) ions. This inhibits protonation of MO in the immediate vicinity
      of the clay. The presence of CDs, however, perturbs the favored process of proton
      scavenging by the clay. In particular, in betaCD-clay systems, betaCD-complexed
      MO can compete successfully with the clay for H(+) ions. The shielding effect of
      betaCD appears to play a key role in preventing the deprotonation of complexed
      MO. Copyright 2001 Academic Press. 

PMID- 11334531
TI  - Effect of Bulk and Interfacial Rheological Properties on Bubble Dissolution.
AB  - This paper describes theoretical calculations of the combined effect of bulk and
      interfacial rheological properties on dissolution behavior of a bubble in an
      infinite medium at saturated conditions. Either bulk or interfacial elasticity
      can stop the bubble dissolution process, and stability criteria are defined for
      the elastic cases. In the case of an elastic interface with dilation modulus E(d)
      and a bubble with an initial radius R(0) and initial interfacial tension
      sigma(0), the bubble is stabilized as it has shrunk to a relative radius of
      varepsilon=R/R(0)=exp(-sigma(0)/2E(d))). In case of an elastic bulk with modulus
      G a bubble will shrink until GR(0)=4sigma(0)varepsilon(3)/(1
      5varepsilon(4)+4varepsilon(3)) is fulfilled. Bulk and interfacial viscosity can
      retard the dissolution process if their magnitude exceeds a certain critical
      value but will never completely stop bubble dissolution. Copyright 2001 Academic
      Press. 

PMID- 11334532
TI  - Thermodynamics of
AB  - Formation of cobalt(II)-thiocyanato complexes in nonionic surfactant solutions of
      poly(ethylene oxide) type with varying poly(ethylene oxide) chain lengths of 7.5
      (Triton X-114), 30 (Triton X-305), and 40 (Triton X-405) has been studied by
      titration spectrophotometry and calorimetry at 298 K. Data were analyzed by
      assuming formation of a series of ternary complexes Co(NCS)(n)Y(m)((2-n)+)
      (Y=surfactant) with an overall formation constant beta(nm). In all the surfactant
      systems examined, data obtained can be explained well in terms of formation of
      Co(NCS)(+) and Co(NCS)(2) in an aqueous phase (aq), and Co(NCS)(4)Y(2-) in
      micelles, and their formation constants, enthalpies, and entropies have been
      determined. The beta(41)/beta(20) ratio increases and the corresponding enthalpy
      becomes significantly less negative with an increasing number of ethylene oxide
      groups. This suggests that micelles of these nonionic surfactants have a
      heterogeneous inner structure consisting of ethylene oxide and octylphenyl
      moieties. Indeed, on the basis of molar volumes of ethylene oxide and octylphenyl
      groups, intrinsic thermodynamic parameters have been extracted for the reaction
      Co(NCS)(2)(aq)+2NCS(-)(aq)=Co(NCS)(4)Y(2-) (Delta(r)G degrees, Delta(r)H degrees,
      and Delta(r)S degrees ) at each moiety. The Delta(r)G degrees, Delta(r)H degrees,
      and Delta(r)S degrees values are -16 kJ mol(-1), -15 kJ mol(-1), and 3 J K(-1)
      mol(-1), respectively, for the ethylene oxide moiety, and -15 kJ mol(-1), -70 kJ
      mol(-1), and -183 J K(-1) mol(-1) for octylphenyl. Significantly less negative
      Delta(r)H degrees and Delta(r)S degrees values for ethylene oxide imply that the
      hydrogen-bonded network structure of water is extensively formed at the ethylene
      oxide moiety, and the structure is thus broken around the Co(NCS)(4)(2-) complex
      with weak hydrogen-bonding ability. Copyright 2001 Academic Press. 

PMID- 11334533
TI  - Molecular Simulation of Interlayer Structure and Dynamics in 12.4 A Cs-Smectite
      Hydrates.
AB  - A detailed understanding of hydrated Cs-smectites is necessary to predict the
      permeability of clay liners to radiocesium cations at nuclear waste containment
      facilities. Monte Carlo (MC) and molecular dynamics (MD) modeling techniques were
      applied to three representative Cs-smectites to interpret a variety of
      experimental data on interlayer structure and dynamics. Spectroscopic and surface
      chemistry methods that attempt to differentiate interlayer water from water
      residing in micropores have provided data suggesting that, in stable 12.4 A Cs
      smectite hydrates, the interlamellar water content is less than one-half
      monolayer. Convergence profiles in MC simulations predicted stable hydrates at
      interlayer water contents of 1/3 or possibly 2/3 water monolayer. Radial
      distribution functions and coordination number data illustrated the ability of
      Cs(+) to organize water molecules into partial hydration shells and displayed the
      distortions of water structure induced by the clay surface. Molecular dynamics
      simulations of the MC-stable Cs-smectites revealed interlayer Cs(+) to be
      strongly bound as innersphere surface complexes, in agreement with published bulk
      diffusion coefficients. The strongly adsorbed Cs(+) can be associated with one of
      the species identified in (133)Cs NMR spectroscopic studies of hydrated Cs
      smectites. These cations typically exhibited jump diffusion, whereas continuous
      diffusion of H(2)O occurred. Copyright 2001 Academic Press. 

PMID- 11334534
TI  - Determination of Surface Dilational Viscosity Using the Oscillating Bubble
      Method.
AB  - A new version of the oscillating bubble method enables us to determine the
      dilational modulus of fluid surfaces in the frequency range 1 Hz</=f</=500 Hz.
      The frequency behavior of this complex modulus exhibits the influence of various
      physical effects which requires explanation in the framework of an appropriate
      theoretical model. For the evaluation of our measurements a theoretical modulus
      is used which includes compositional and intrinsic viscous effects. The
      compositional effects are described by the established model of dynamic surface
      tension. However, a modified interpretation is required to explain the values of
      the involved parameters which deviate strongly from the values calculated using
      equilibrium data. In addition, several experiments demonstrate the influence of
      an intrinsic surface dilational viscosity. This can be interpreted as the effect
      of molecular exchange at the surface in a nonequilibrium state. For the
      investigation of such processes we have compared the surface dilational moduli of
      solutions of alkyldimethylphosphine oxides with various chain lengths. The
      theoretical model was tested using these experimental results. It was possible to
      determine the parameters of the model. The parameters characterize the elastic
      and viscous properties of the surface as well as molecular exchange processes
      between surface and bulk. Their values mark scales for the influence of
      compositional effects, intrinsic effects, and molecular kinetics on the
      dilational properties of the surface. Copyright 2001 Academic Press. 

PMID- 11334535
TI  - The Level of Hydrophobic Substitution and the Molecular Weight of Amphiphilic
      Poly-L-lysine-Based Polymers Strongly Affects Their Assembly into Polymeric
      Bilayer Vesicles.
AB  - With the aim of producing new materials for drug and gene delivery, the variables
      associated with the preparation of poly-L-lysine-based vesicles were
      investigated. Amphiphilic poly-L-lysine graft copolymers with varying levels of
      grafted methoxypolyethylene glycol (mPEG) and palmitic acid were synthesized
      using two-step grafting reactions of the macromonomer, mPEG-p-nitrophenyl
      carbonate (mPEG, MW=5,000), and palmitic acid N-hydroxysuccinimide ester onto
      poly-L-lysine hydrobromide (MW=4,000 and 19,600). Polymers were characterized by
      gel permeation chromatography/light scattering. (1)H NMR, and an assay for
      unreacted varepsilon-amino groups. Polymeric unilamellar vesicles were produced
      by probe sonication of the amphiphilic poly-L-lysine-based polymers in the
      presence of cholesterol. Vesicles were characterized by electron microscopy and
      photon correlation spectroscopy. Vesicle formation was favored by a low molecular
      weight and a low level of palmitoyl substitution. A vesicle formation index has
      been derived, F ~ H/L DP, where H is the %molar level of unreacted L-lysine
      units, L is the %molar level of substituted palmitoyl units, and DP is the square
      root of the degree of polymerization of the polymer. Additionally, the size of
      these vesicles may be controlled by controlling the initial molecular weight of
      the parent poly-L-lysine/resulting amphiphilic polymer. Hence, amphiphilic poly-L
      lysine-based polymers of molecular weight=89,000 and 25,000 produced polymeric
      vesicles of z-average mean diameter 570 nm and 252 nm, respectively. Vesicle
      encapsulation efficiency for the hydrophilic macromolecule, fluorescein
      isothiocyanate-dextran (MW=4,400), increased with vesicle size. Copyright 2001
      Academic Press. 

PMID- 11334536
TI  - Microflotation Suppression and Enhancement Caused by Particle/Bubble
      Electrostatic Interaction.
AB  - The processes of attachment and detachment of small or medium-sized particles to
      relatively large bubbles during microflotation are considered in terms of the
      heterocoagulation theory. Calculations are made for the conditions that the
      surface potentials are of similar sign and constant, that one of the surface
      potentials is small, that hydrophobic attraction is absent, and that there are no
      surface deformations. Under these conditions bubble-particle aggregates may form
      as a result of an electrostatic attraction which exceeds the repulsive van der
      Waals force at intermediate distances. Next to electrostatic and van der Waals
      forces, hydrodynamic and gravitational forces are considered. These forces may
      overcome the electrostatic repulsion at large distances and promote particle
      bubble attachment. Strong electrostatic attraction at small distances, arising at
      a large difference of the surface potentials of the bubble and the particle and
      of low electrolyte concentrations, can prevent subsequent detachment by
      hydrodynamic and gravitational forces. With increasing electrolyte concentration
      the electrostatic barrier increases and the attractive electrostatic force
      diminishes. As a result, a critical electrolyte concentration for microflotation
      exists. Above this concentration attachment may still occur but it is followed by
      detachment. At lower electrolyte concentrations the electrostatic attractive
      force prevents the detachment. The dependence of the critical electrolyte
      concentration on the values of the bubble and particle potentials and the Hamaker
      constant is calculated. The critical concentration does not depend on particle or
      bubble size if the absolute values of the total detachment force and the total
      pressing force coincide, which is the case for Stokes and potential flow. For
      every electrolyte concentration lower than the critical value there are two
      critical particle sizes that limit the flotation possibility. For small particle
      sizes attachment is impossible because the pressing force is smaller than the
      electrostatic barrier. For large particle sizes detachment cannot be prevented
      because the detachment force exceeds the maximum electrostatic attraction. A
      microflotation domain of intermediate particle sizes exists in which irreversible
      heterocoagulation occurs. Copyright 2001 Academic Press. 

PMID- 11334537
TI  - Occurrence of an Intermediate Relaxation Process in Water-in-Oil Microemulsions
      below Percolation: The Electrical Modulus Formalism.
AB  - The dielectric and conductometric spectra of water-in-oil microemulsions below
      percolation in the frequency range from 1 MHz to 1.8 GHz have been analyzed on
      the basis of the electrical modulus formalism. In the frequency range
      investigated, this approach clearly evidences the presence of a particular
      polarization mechanism, resulting in a well-defined dielectric dispersion,
      located between that due to the orientational polarization of the bulk aqueous
      phase and that due to the ionic structure of the interface, usually occurring in
      heterogeneous systems. This polarization mechanism has been attributed to the "in
      phase" correlation displacement of surfactant polar head groups surrounding each
      water droplet dispersed in the oil phase. This mechanism differs from the usual
      interfacial Maxwell-Wagner effect. The advantage of the electrical modulus
      formalism, in comparison with the analysis of the directly measured quantities,
      the permittivity epsilon'(omega), and the total electrical conductivity
      sigma(omega), are briefly discussed. Copyright 2001 Academic Press. 

PMID- 11334538
TI  - Theoretical Study of Aerosol Filtration by Nucleopore Filters: The Intermediate
      Crossover Regime of Brownian Diffusion and Direct Interception.
AB  - We study the problem of aerosol filtration by formulating a unified approach that
      incorporates the dominant mechanisms of particle capture in cylindrical pores.
      The theoretical approach presented here takes into account the effects of flow
      slip at the pore wall and predicts an enhanced efficiency in the intermediate
      crossover regime between Brownian diffusion and direct interception. We also
      suggest how the results obtained for cylindrical pores can be used to estimate
      the efficiency of granular ceramic filters in the region of the most penetrating
      particle size, where the enhanced efficiency effects are strongly amplified by
      the large number of pores, or more generally unit bed elements, acting in series.
      Copyright 2001 Academic Press. 

PMID- 11334539
TI  - Production of Oil-in-Water Microspheres Using a Stainless Steel Microchannel.
AB  - From the point of view of practical application of the microchannel (MC)
      emulsification technique, which can be used to produce super-monodispersed
      microspheres (MS), we fabricated a stainless steel MC and investigated the
      production and characterization of oil-in-water (O/W) MS using a stainless steel
      MC instead of a silicon MC plate. We discovered that a stainless steel MC could
      not be fabricated precisely at a 1-&mgr;m scale; because of its multicrystal
      property, it can only be processed mechanically on a 10-&mgr;m scale. O/W-MS
      ranging from 20 to 210 &mgr;m in average diameter were produced using a stainless
      steel MC with 10 to 80 &mgr;m in equivalent diameter. The MS produced were
      monodispersed with a coefficient of variation lower than 3% for each individual
      channel. This value is smaller than that of normal emulsions obtained by the
      conventional emulsification techniques by 1 order of magnitude. The average
      diameter of the MS produced at breakthrough pressure was about 2.6 times the
      stainless steel MC equivalent diameter. The operation pressure affects the MS
      formation, causing a size-stable zone, size-expanding zone, and outflow zone
      observed. Larger stainless steel MC demonstrated difficulties in stably producing
      monodispersed O/W-MS. The breakthrough pressure was approximately inversely
      proportional to the MC equivalent diameter. Copyright 2001 Academic Press. 

PMID- 11334540
TI  - Origins of the Non-DLVO Force between Glass Surfaces in Aqueous Solution.
AB  - Direct measurement of surface forces has revealed that silica surfaces seem to
      have a short-range repulsion that is not accounted for in classical DLVO theory.
      The two leading hypotheses for the origin of the non-DLVO force are (i)
      structuring of water at the silica interface or (ii) water penetration into the
      surface resulting in a gel layer. In this article, the interaction of silica
      surfaces will be reviewed from the perspective of the non-DLVO force origin. In
      an attempt to more accurately describe the behavior of silica and glass surfaces,
      alternative models of how surfaces with gel layers should interact are proposed.
      It is suggested that a lessened van der Waals attraction originating from a thin
      gel layer may explain both the additional stability and the coagulation behavior
      of silica. It is important to understand the mechanisms underlying the existence
      of the non-DLVO force which is likely to have a major influence on the adsorption
      of polymers and surfactants used to modify the silica surface for practical
      applications in the ceramic, mineral, and microelectronic industries. Copyright
      2001 Academic Press. 

PMID- 11334541
TI  - Spontaneous Emulsification Produced by Chemical Reactions.
AB  - Spontaneous emulsification of small oil droplets was produced in three different
      systems by chemical reactions which converted lipophilic surfactants initially
      dissolved in the oil phase to hydrophilic surfactants. The resulting reversal of
      spontaneous curvature from a water-in-oil to an oil-in-water configuration
      reduced the solubilization capacity for oil to such an extent that
      supersaturation occurred, leading to nucleation of oil droplets. In one case a
      dilute solution of phenylboronic acid in water diffused into an oil phase
      containing a monoglyceride. The reaction converted the monoglyceride to an
      anionic surfactant. In another case a dilute aqueous solution of the sodium salt
      of EDTA diffused into an oil phase containing a calcium sulfonate surfactant. The
      EDTA complexed calcium ions, releasing sodium ions which formed the more
      hydrophilic sodium salt of the sulfonate. Finally, an enzyme was used to split a
      double-chain phospholipid into a lysolecithin and a fatty acid. Copyright 2001
      Academic Press. 

PMID- 11334542
TI  - The Role of Viscoelastic Adhesive Contact in the Sintering of Polymeric
      Particles.
AB  - The sintering of polymeric particles is analyzed by considering the growth of
      contact between viscoelastic spheres driven by adhesive intersurface forces. This
      process is dominant during the initial phase of sintering and is succeeded by a
      viscous sintering step that is driven by surface tension and accommodated by
      viscous flow. The intersurface forces in this work are described by a cohesive
      zone model. A new formulation of adhesive contact that does not require the
      cohesive zone to be smaller than the contact radius, together with finite element
      simulations is used to study the growth of contact. The results of this paper
      establish conditions that determine the dominant mechanism of contact growth
      during sintering. These conditions are described using a "deformation map". For a
      Maxwell material, if particle radius R(max),</=20delta(c), where delta(c) is a
      characteristic separation in the Dugdale-Barenblatt model, then the coalescence
      is driven by adhesive intersurface forces. Copyright 2001 Academic Press. 

PMID- 11334543
TI  - Streaming Potential and Streaming Current Methods for Characterizing
      Heterogeneous Solid Surfaces.
AB  - By monitoring changes in electrokinetic parameters, the streaming potential
      technique has been used as a method of characterizing heterogeneous surfaces, for
      example, due to protein adsorption. In general it is assumed that the change in
      the streaming potential is proportional to the degree of heterogeneity. In this
      study a simple model of the electrokinetic flow through heterogeneous slit
      channels has been developed with the goal of comparing the streaming potential
      and streaming current techniques and determining under what conditions the
      aforementioned proportionality assumption will produce erroneous results. The
      flow simulations have shown that, when the streaming potential induces
      significant flow impedance, a severe deviation from the linear assumption is
      observed. Since streaming current measurements are unaffected by electrokinetic
      flow effects, more consistent results are predicted and they are preferred for
      measurements made in small channels. Additionally it has been shown that the
      distribution of the heterogeneous coverage has a negligible effect on both the
      streaming potential and the streaming current in cases where the double-layer
      overlap is not significant. Copyright 2001 Academic Press. 

PMID- 11334544
TI  - Pt- (and Co-) Promoted Molybdena-Alumina Catalysts: Analysis of the Impregnation
      Steps.
AB  - The equilibrium parameters for the adsorption of Mo(VI) on gamma-Al(2)O(3) and of
      Co(II) and Pt(IV) on MoO(3)/gamma-Al(2)O(3) were determined. The adsorption
      isotherms were performed from aqueous solutions of the corresponding precursors
      on two different alumina supports. According to the classification given by
      Giles, L-type-shaped, subgroup 2, adsorption curves were found for the system Mo
      on gamma-Al(2)O(3), L-type, subgroup 1, for the Pt on MoO(3)/gamma-Al(2)O(3), and
      S-type for Co on the MoO(3)/gamma-Al(2)O(3) system. Numerical calculations were
      carried out for all the isotherms to find the equilibrium parameters. These
      constants are being used to model the development of Pt, Co, and Mo profiles on
      MoO(3)/gamma-Al(2)O(3) or gamma-Al(2)O(3) extrudates, respectively, which belong
      to the new generation of noble-metal-MoO(3)/gamma-Al(2)O(3)-supported catalysts
      to be used in oil-refining processes. Copyright 2001 Academic Press. 

PMID- 11334545
TI  - Diffusion-Controlled Adsorption at the Liquid-Air Interface: The Long-Time Limit.
AB  - The applicability of the Hansen and Joos long-time limits for the dynamic surface
      tension of solutions is investigated by regressing diffusion coefficients from
      numerical solutions to the Ward and Tordai equation. The Hansen limit is found to
      correctly describe the dynamic surface tension evolutions at long times. However,
      both the surfactant concentration and the adsorption time affect the accuracy of
      the long-time limit. The study also indicates that, because the reduction in
      surface tension (at long times) may be smaller than can be measured by current
      tensiometry methods, the application of the Hansen limit to long-time data may
      not always be feasible. Copyright 2001 Academic Press. 

PMID- 11334546
TI  - Oxide Surface Behavior in Aqueous Electrolytes: An Example of Inconsistent
      Modeling.
AB  - A recent article by N. Marmier and F. Fromage (2000, J. Colloid. Interface Sci.
      223, 83) predicts the sorption of Cs onto mixtures of silica and magnetite.
      Despite experimental confirmation of their prediction, the underlying theoretical
      model is inconsistent both with the authors' previous theoretical model and with
      other experimental data. Copyright 2001 Academic Press. 

PMID- 11334547
TI  - Using CCM for the Prediction of Sorption Curves under Varying Ionic Strength
      Conditions: Reply to Some Comments.
AB  - In response to the comments of J. Lutzenkirchen (237, 297 (2001), J. Colloid
      Interface Science), it is pointed out that the criticized model is not intended
      to provide a complete description of the system studied (Cs on silica-magnetite).
      Rather, it is a simplification of a complex natural system. The accuracy of the
      obtained predictions requires further investigation. Copyright 2001 Academic
      Press. 

PMID- 11334548
TI  - Role of gamma-linolenic acid in counteracting doxorubicin-induced damage in
      cultured rat cardiomyocytes.
AB  - The clinical usefulness of doxorubicin is limited by cardiotoxicity. We have
      demonstrated that doxorubicin has a dual negative effect on myocardial lipids,
      acting against highly unsaturated fatty acids (HUFAs) directly and
      desaturating/elongating enzymes required for their biosynthesis, thus decreasing
      linoleic and alpha -linolenic conversion to higher metabolites. Primary cultures
      of rat cardiomyocytes were challenged with different doxorubicin concentrations
      and doxorubicin exposure was followed by a 24-h recovery period in the absence or
      presence of serum, and of gamma -linolenic acid. Serum in the recovery medium did
      not appear to be essential for the restoration of the desaturating/elongating
      activities, and gamma -linolenic acid supplementation influenced only alpha 
      linolenic acid conversion. Serum, and particularly gamma-linolenic acid, were
      very important in increasing HUFA levels behind the pure biosynthesis. HUFA
      biosynthesis plays a role in counteracting doxorubicin toxicity, but it cannot
      completely overcome the depletion of these fatty acids; serum and exogenous gamma
      linolenate are critical in filling the decreased HUFA pool.

PMID- 11334549
TI  - Modulation of intestinal vitamin D receptor availability and calcium ATPase
      activity by essential fatty acids.
AB  - The physiological mechanisms by which essential fatty acids (EFAs) affect calcium
      (Ca(2+)) retention is not clear, but suggestions have included changes in
      membrane fluidity, receptor modulation and induction of second messengers. The
      vitamin D receptor (VDR) is essential for the functioning of 1,25(OH)(2)D(3)which
      increases Ca(2+)absorption. Activity of the intestinal basolateral membrane (BLM)
      Ca(2+)ATPase correlates with the degree of Ca(2+)absorption. Therefore, changes
      in ATPase activity and VDR availability due to EFAs may influence calcium
      retention. We have investigated the effect of long-term dietary supplementation
      with EFAs on Ca(2+)ATPase activity (measured colourimetrically) and VDR
      availability (measured with the ELISA technique) after the loss of oestrogen
      induced by ovariectomy (OVX) in female Sprague Dawley rats. Control animals
      underwent anaesthesia and a surgical procedure but the ovaries were left intact
      (sham). Ca(2+)ATPase activity was significantly lower in OVX animals than in the
      intact animals (P<0.05) and following supplementation with EFAs, was
      significantly higher than in sham controls (P<0.05). A higher number of VDR was
      measured after OVX and declined due to EFA supplementation; these differences in
      activity of the ATPase and number of receptors could be ascribed to membrane
      changes due to EFA supplementation, feedback control by serum calcium or the
      direct influence of the EFAs.

PMID- 11334550
TI  - Dietary polyunsatured fatty acids (PUFA) differentially modulate melamine-induced
      preneoplastic urothelial proliferation and apoptosis in mice.
AB  - A number of experimental and epidemiological studies indicate that dietary
      polyunsaturated fatty acids (PUFA) play a modulatory role in the development of
      several cancers. However, literature on the importance of dietary PUFA in urinary
      tract tumourigenesis is scarce, and even contradictory. Therefore, our purpose
      was to evaluate comparatively, several urothelial cellular parameters linked to
      neoplasia when 180 BALB/c mice were initiated with the tumourigenic agent
      melamine and fed with two amounts of different PUFA. In experiment 1, mice were
      fed with 6% of fish oil (enriched in n-3 PUFA, FO), corn oil (enriched in n-6,
      CO) and olein (enriched in n-9, an EFA deficiency inducer) formulae plus two chow
      fed control lots with (CM) and without (C) melamine treatment. In experiment 2,
      each of the three varieties of PUFA were offered at 10%. Following 18-22 weeks of
      melamine treatment, animals were autopsied. The liver fatty acid profile showed a
      close correlation with the dietary sources, exhibiting in the O group macroscopic
      and biochemical EFA-deficient (EFAD) characteristics. The frequency of simple
      urothelial hyperplasias (H) and dysplasia/carcinoma in situ (D/CIS) was
      significantly lower in the FO group, whereas both types of lesions increased in
      the CO and O groups, compared to the C and CM mice. Increased proliferation and
      abnormal luminal localized mitosis were more frequently recorded in EFAD mice,
      whereas abnormal apoptotic/mitosis ratio increased in both olein- and corn-oil
      fed animals. This study shows that dietary PUFA modulate differentially normal
      and pre-neoplastic proliferation when induced by the tumorigenic agent melamine.
      Fish oil, rich in n-3 fatty acids, exhibits a clear antipromoting activity,
      whereas the role of n-6 and n-9 PUFA derivatives needs further research.

PMID- 11334551
TI  - Transcardiac 8-iso-prostaglandin F(2 alpha)generation from acute myocardial
      infarction heart: insight into abrupt reperfusion and oxidant stress.
AB  - 8-iso-prostaglandin F(2 alpha)(8-iso-PGF(2 alpha)), a representative isoprostane,
      has been reported to be a reliable marker for oxidant stress in vivo. To examine
      if 8-iso-PGF(2 alpha)is generated in patients with acute myocardial infarction
      (AMI), we measured the level of immunoreactive 8-iso PGF(2 alpha)in the great
      cardiac vein as well as classical eicosanoids, 6-keto-prostaglandin F(1 alpha)(6
      keto-PGF(1 alpha)) and thromboxane B(2)(TXB(2)) in the process of urgent coronary
      balloon angioplasty. Fourteen patients with anterior AMI were divided into two
      groups: the totally occluded (n=7) and the already perfused groups (n=7). In the
      former, transient elevation of 8-iso-PGF(2 alpha)was observed immediately after
      the angioplasty, i.e. the ratio of post-angioplasty level to pre-level was
      approximately 2.4 for 8-iso-PGF(2 alpha), 14 for 6-keto-PGF(1 alpha), and 5 for
      TXB(2). In the already perfused group, the levels of these eicosanoids were
      unchanged. In the totally occluded group, peak creatine phosphokinase in a
      peripheral vein was correlated with the level of 8-iso-PGF(2 alpha)(r(2)=0.841,
      P<0.01), but not with those of the other two eicosanoids. In conclusion,
      transcardiac 8-iso-PGF(2 alpha)generation is a reliable marker for the size of
      myocardium exposed to oxidant stress.

PMID- 11334552
TI  - 6-oxo-PGF(1 alpha)and 8-epi-PGF(2 alpha)in the arterial wall layers of various
      species: a comparison between intact and atherosclerotic areas.
AB  - PGI(2)and 8-epi-prostaglandin(PG)F(2 alpha)are antagonizing compounds. For both a
      key role in vascular pathology has been hypothesized. The isoprostane 8-epi-PGF(2
      alpha)and the stable derivative of PGI(2), 6-oxo-PGF(1 alpha)were determined
      immunologically in the arterial wall of various species including humans. Human
      arterial tissue contained the highest amounts of 8-epi-PGF(2 alpha)and
      synthesized the lowest PGI(2). A significant negative correlation between 8-epi
      PGF(2 alpha)and 6-oxo-PGF(1 alpha)was observed. Atherosclerotic segments showed
      significantly higher 8-epi-PGF(2 alpha)and lower 6-oxo-PGF(1 alpha). 8-epi-PGF(2
      alpha)in the intima was higher than in the media, the highest amounts being found
      in foam-cell rich areas. Synthetic (activated) smooth muscle cells were
      associated with an enhanced 8-epi-PGF(2 alpha)as well as 6-oxo-PGF(1 alpha).
      Tissue samples derived from smokers contained more 8-epi-PGF(2 alpha)and produced
      less PGI(2). The by far highest 8-epi-PGF(2 alpha)/6-oxo-PGF(1 alpha)ratio was
      found in foam cell rich areas. Similar findings were obtained in rabbit and in
      minipig arteries. The total 8-epi-PGF(2 alpha)/6-oxo-PGF(1 alpha)ratio is low in
      normal tissue, increases significantly in an active atherosclerotic process and
      seems to be even further increased in an inactive atherosclerotic process. These
      findings are providing an information on the extent of oxidation injury at
      various sites of different types of atherosclerotic process.

PMID- 11334553
TI  - Could platelet activating factor play a role in developmental dyslexia?
AB  - Post-mortem studies by Galaburda and colleagues on the brains of developmental
      dyslexics found characteristic neuronal abnormalities: ectopias, microgyria, and
      fewer large-soma cells in sensory thalamus. An association between dyslexia and
      immune dysfunction has also been proposed. We describe a mechanism which may
      explain these observations. Platelet-activating factor (PAF) is a pro
      inflammatory lipid implicated in neurological disorders. We propose that PAF may
      also be involved in dyslexia.

PMID- 11334554
TI  - The effect of dietary polyunsaturated fatty acid on insulin sensitivity and lipid
      metabolism in Otsuka Long-Evans Tokushima Fatty (OLETF) rats.
AB  - The effects of insulin sensitivity and lipid metabolism of dietary lard,
      eicosapentaenoic acid-rich oil (EPA oil) or arachidonic acid oil (AA oil) in
      Otsuka Long-Evans Tokushima Fatty (OLETF) rats were examined. Blood glucose was
      not different in each group at 30, 60, 120 min on an oral glucose tolerance test.
      Fasting blood glucose levels were lower in lard and AA oil groups than in
      controls. Hepatic triglyceride concentration and liver histochemistry revealed
      that the fat content was higher in the lard group and the AA oil group than in
      controls. The EPA oil group showed TG levels as high as the control group. Serum
      total cholesterol in the EPA oil group was lower, while the level in the AA oil
      group was higher than in the lard and control groups. HDL cholesterol was 1.5
      fold higher in the AA oil group than in controls. Dietary EPA oil or AA oil
      supplementation showed different effects on lipid metabolism in this model.

PMID- 11334555
TI  - Brain and hippocampus fatty acid composition in phospholipid classes of aged
      relative cognitive deficit rats.
AB  - The aim of this work was to study the composition of long chain fatty acids and
      the n-6 and n-3 fatty acid ratios in aged and young Wistar rats in brain and
      hippocampus, related to relative cognitive deficits. The aged animals showed
      cognitive deficits during acquisition of a memory task (delayed alternation). In
      brain, results showed a decrease in palmitoleic and palmitic acid percentages in
      all the studied phospholipid classes and in the phosphatidylserine and
      phosphatidylcholine classes, respectively, in old rats, compared to the young
      ones. There was also an increase in oleic and stearic acid amounts in the
      sphingomyelin, phosphatidylserine and phosphatidylinositol classes and in the
      phosphatidylserine and phosphatidylcholine classes, respectively. Arachidonic
      acid amount was decreased in old rats, compared to the young ones, in the
      phosphatidylserine and phosphatidylinositol classes. Total n-6 and n-3 fatty acid
      amounts were both decreased in all phospholipid classes, with a stable n-6/n-3
      ratio. Our results confirm that arachidonic acid concentration is decreased in
      aged rats and that this reduction, more significant in phosphatidylserine and
      phosphatidylinositol classes, should be related to the fact that low
      concentrations of arachidonic acid are observed during activation of glutamate
      receptor.

PMID- 11334556
TI  - Comparative effects of beraprost, a stable analogue of prostacyclin, with PGE(1),
      nitroglycerin and nifedipine on canine model of vasoconstrictive pulmonary
      hypertension.
AB  - Acute hemodynamic effects of beraprost sodium were tested in a canine
      vasoconstrictive pulmonary hypertension model induced by the continuous infusion
      of U-46619, a thromboxane A(2)mimetic. The effects of beraprost were compared
      with those of prostaglandin E(1), nitroglycerin and nifedipine. Beraprost and
      nitroglycerin decreased pulmonary arterial pressure. On the other hand,
      prostaglandin E(1)and nifedipine increased pulmonary arterial pressure. All drugs
      except nitroglycerin increased cardiac output and decreased pulmonary vascular
      resistance. Beraprost was selective to pulmonary circulation, while
      nitroglycerin, prostaglandin E(1), and nifedipine showed poor selectivity for the
      pulmonary vasculature. These results suggest that the vasodilative effect of
      beraprost is the most selective for the pulmonary circulation among these four
      vasodilators.

PMID- 11334557
TI  - Characterization of the prostaglandin receptors in human osteoblasts in culture.
AB  - Prostaglandins have complex actions on bone metabolism that depend on
      interactions with different types and subtypes of receptors. Our objective was to
      characterize the prostaglandins receptors present in primary cultures of human
      osteoblasts. RT-PCR analysis revealed the presence of DP, EP(4), IP, FP and TP
      receptor mRNA in primary cultures of human osteoblasts. FP receptor mRNA was
      detected only after 3 weeks of confluency, all the others were detected at every
      culture time tested. To verify the functionality of these receptors we challenged
      the cells with the prostanoids and synthetic analogues and determined the
      intracellular levels of cAMP. All receptors found by RT-PCR were coupled to
      second messengers except for the DP subtype. These results clearly show the
      presence of functional EP(4), IP, FP and TP receptors in human osteoblasts in
      culture.

PMID- 11334558
TI  - Highly selective and potent neuropeptide Y (NPY) Y1 receptor antagonists based on
      [Pro(30), Tyr(32), Leu(34)]NPY(28-36)-NH2 (BW1911U90).

PMID- 11334559
TI  - Flexible alignment of small molecules.
AB  - A method is presented for flexibly aligning small molecules. The method accepts a
      collection of small molecules with 3D coordinates as input and computes a
      collection of alignments. Each alignment is given a score, which quantifies the
      quality of the alignment both in terms of internal strain and overlap of
      molecular features. The results of several computational experiments on pairs of
      compounds with known binding conformations are used to systematically and
      objectively tune the parameters for the method. The results indicate the method's
      utility for the elucidation of pharmacophores and comparative field analysis.

PMID- 11334560
TI  - Design, synthesis, and proposed active site binding analysis of monocyclic 2
      azetidinone inhibitors of prostate specific antigen.
AB  - A homology derived molecular model of prostate specific antigen (PSA) was created
      and refined. The active site region was investigated for specific interacting
      functionality and a binding model postulated for the novel 2-azetidinone acyl
      enzyme inhibitor 1 (IC(50) = 8.98 +/- 0.90 microM) which was used as a lead
      compound in this study. A single low energy conformation structure II (Figure 2)
      was adopted as most likely to represent binding after minimization and dynamics
      calculations. Systematic analysis of the binding importance of all three side
      chains appended to the 2-azetidinone was conducted by the synthesis of several
      analogues. A proposed salt bridge to Lys-145 with 4 (IC(50) = 5.84 +/- 0.92
      microM) gave improved inhibition, but generally the binding of the N-1 side chain
      in a specific secondary aromatic binding site did not tolerate much structural
      alteration. A hydrophobic interaction of the C-4 side chain afforded inhibitor 6
      (IC(50) = 1.43 +/- 0.19 microM), and polar functionality could also be added in a
      proposed interaction with Gln-166 in 5 (IC(50) = 1.34 +/- 0.05 microM). Reversal
      of the C-4 ester connectivity furnished inhibitors 7 (IC(50) = 1.59 +/- 0.15
      microM), 11 (IC(50) = 3.08 +/- 0.41 microM), and 13 (IC(50) = 2.19 +/- 0.36
      microM) which were perceived to bind to PSA by a rotation of 180 degrees relative
      to the C-4 ester of normal connectivity. Incorporation of hydroxyl functionality
      into the C-3 side chain provided 16 (IC(50) = 348 +/- 50 nM) with the greatest
      increase in PSA inhibition by a single modification. Multiple copy simultaneous
      search (MCSS) analysis of the PSA active site further supported our model and
      suggested that 18 would bind strongly. Asymmetric synthesis yielded 18 (IC(50) =
      226 +/- 10 nM) as the most potent inhibitor of PSA reported to date. It is
      concluded that our design approach has been successful in developing PSA
      inhibitors and could also be applied to the inhibition of other enzymes,
      especially in the absence of crystallographic information.

PMID- 11334561
TI  - Synthesis of 2beta-acyl-3beta-(substituted naphthyl)-8-azabicyclo[3.2.1]octanes
      and their binding affinities at dopamine and serotonin transport sites.
AB  - A series of 3beta-naphthyltropane derivatives were synthesized and found to show
      high affinity at both the dopamine and serotonin transporter sites, leading to
      some of the most potent inhibitors known based on the tropane structure.
      Comparative molecular field analysis (CoMFA) models were developed for both
      dopamine and serotonin transporter binding data. These models provide insights
      into those factors that influence binding at the two transporters.

PMID- 11334562
TI  - Design, synthesis, SAR, and biological evaluation of highly potent benzimidazole
      spaced phosphono-alpha-amino acid competitive NMDA antagonists of the AP-6 type.
AB  - A series of 2-amino-(phosphonoalkyl)-1H-benzimidazole-2-alkanoic acids was
      synthesized and evaluated for NMDA receptor affinity using a [3H]CPP binding
      assay. Functional antagonism of the NMDA receptor complex was evaluated in vitro
      using a stimulated [3H]TCP binding assay and in vivo by employing an NMDA-induced
      seizure model. Several compounds of the AP-6 type demonstrated potent and
      selective NMDA antagonistic activity both in vitro and in vivo. In particular,
      [R(-)]-2-amino-3-(5-chloro-1-phosphonomethyl-1H-benzoimidazol-2-yl)-propionic
      acid (1) displayed an IC(50) value of 7.1 nM in the [3H]CPP binding assay and an
      ED(50) value of 0.13 mg/kg (ip) in the NMDA lethality model. Compound 1, when
      administered intravenously as a single bolus dose of 3 mg/kg following permanent
      occlusion of the middle cerebral artery in the rat, reduced the volume of
      infarcted brain tissue by 45%. These results support a promising therapeutic
      potential for compound 1 as a neuroprotective agent.

PMID- 11334563
TI  - Computational analysis of PKA-balanol interactions.
AB  - Protein kinases are important targets for designing therapeutic drugs. This paper
      illustrates a computational approach to extend the usefulness of a single protein
      inhibitor structure in aiding the design of protein kinase inhibitors. Using the
      complex structure of the catalytic subunit of PKA (cPKA) and balanol as a guide,
      we have analyzed and compared the distribution of amino acid types near the
      protein-ligand interface for nearly 400 kinases. This analysis has identified a
      number of sites that are more variable in amino acid types among the kinases
      analyzed, and these are useful sites to consider in designing specific protein
      kinase inhibitors. On the other hand, we have found kinases whose protein-ligand
      interfaces are similar to that of the cPKA-balanol complex and balanol can be a
      useful lead compound for developing effective inhibitors for these kinases.
      Generally, this approach can help us discover new drug targets for an existing
      class of compounds that have already been well characterized pharmacologically.
      The relative significance of the charge/polarity of residues at the protein
      ligand interface has been quantified by carrying out computational sensitivity
      analysis in which the charge/polarity of an atom or functional group was turned
      off/on, and the resulting effects on binding affinity have been examined. The
      binding affinity was estimated by using an implicit-solvent model in which the
      electrostatic contributions were obtained by solving the Poisson equation and the
      hydrophobic effects were accounted for by using surface-area dependent terms. The
      same sensitivity analysis approach was applied to the ligand balanol to develop a
      pharmacophoric model for searching new drug leads from small-molecule libraries.
      To help evaluate the binding affinity of designed inhibitors before they are
      made, we have developed a semiempirical approach to improve the predictive
      reliability of the implicit-solvent binding model.

PMID- 11334564
TI  - Synthesis, photophysical properties, tumor uptake, and preliminary in vivo
      photosensitizing efficacy of a homologous series of 3-(1'-alkyloxy)ethyl-3
      devinylpurpurin-18-N-alkylimides with variable lipophilicity.
AB  - Starting from methylpheophorbide-a, a homologous series of purpurinimides
      containing alkyl substituents at two different positions [as 3-(1(1)-O-alkyl) and
      13(2)-N-alkyl] were synthesized. These compounds with variable lipophilicity (log
      P 5.32-16.44) exhibit long wavelength absorption near lambda(max)700 nm (epsilon:
      45 000 in dichloromethane) with singlet oxygen ((1)O2) production in the range of
      57-60%. The shifts in in vivo absorptions and tumor/skin uptake of these
      compounds were determined in C3H mice bearing RIF tumors by in vivo reflectance
      spectroscopy. The results obtained from a set of photosensitizers with similar
      lipophilicity (log P 10.68-10.88) indicate that besides the overall
      lipophilicity, the presence and position of the alkyl groups (O-alkyl vs N-alkyl)
      in a molecule play an important role in tumor uptake, tumor selectivity, and in
      vivo PDT efficacy. At present, all purpurinimide analogues are being evaluated at
      various doses, and experiments are underway to establish a quantitative structure
      activity relationship on a limited set of compounds. The 1D and 2D NMR and mass
      spectrometry analyses confirmed the structures of the desired purpurinimides and
      the byproducts formed during various reaction conditions. The mechanisms of the
      formation of the unexpected 12-formyl- and 12-(hydroxymethyl)purpurinimides under
      certain reaction conditions are also discussed.

PMID- 11334565
TI  - Antimycobacterial activity of substituted isosteres of pyridine- and
      pyrazinecarboxylic acids. 2.
AB  - Pyridines and pyrazines substituted with 1,2,4-oxadiazole-5-ones, 1,2,4
      oxadiazole-5-thiones, and 1,3,4-oxathiazoline-2-ones were synthesized and tested
      against Mycobacterium tuberculosis. The two former ring systems were documented
      in the literature to act as carboxylic acid isosteres. The latter series was
      synthesized as possible synthetic intermediates to 1,2,4-thiadiazole-3-ones and
      was included in this study due to their interesting activity. Pivaloyloxymethyl
      derivatives of the isosteres were also prepared in order to increase their
      lipophilicity and therefore improve their cellular permeability. The derivatized
      isosteres were expected to be biotransformed by esterases to the active species
      after penetration of the mycobacterial cell wall. Biological properties of the
      compounds were compared with the unmodified polar isosteres of pyrazinoic and
      nicotinic acids. The majority of the compounds exhibited activities ranging from
      0.5 to 16 times the potency of pyrazinamide.

PMID- 11334566
TI  - Mining the chemical quarry with joint chemical probes: an application of latent
      semantic structure indexing (LaSSI) and TOPOSIM (Dice) to chemical database
      mining.
AB  - In this study we use a novel similarity search technique called latent semantic
      structure indexing (LaSSI) with joint chemical probes as queries to mine the MDL
      drug data report database. LaSSI is based on latent semantic indexing developed
      for searching textual databases. We use atom pair and topological torsion
      descriptors in our calculations. The results obtained with LaSSI are compared
      with another in-house similarity search technique TOPOSIM. The results from the
      similarity searches using joint chemical probes are significantly better than
      searches using single chemical probes for both LaSSI and TOPOSIM. The selected
      molecules are closely related in activity to their queries and are ranked among
      the top 300 scoring molecules of the 82 860 entries in the database. Our
      implementation of LaSSI is very fast and efficient in finding active compounds.
      The results also show that LaSSI consistently retrieves more diverse chemical
      structures representative of the joint chemical probes in comparison to TOPOSIM.
      The use of multimolecule topological probes to identify compounds complements the
      use of searching databases with 3D pharmacophore hypotheses.

PMID- 11334567
TI  - Synthesis and NMR-driven conformational analysis of taxol analogues
      conformationally constrained on the C13 side chain.
AB  - Analogues of Taxol (paclitaxel) with the side chain conformationally restricted
      by insertion of a carbon linker between the 2'-carbon and the ortho-position of
      the 3'-phenyl ring were synthesized. Biological evaluation of these new taxoids
      showed that activity was dependent on the length of the linker and the
      configuration at C2' and C3'. Two analogues in the homo series, 9a and 24a,
      showed tubulin binding and cytotoxicity comparable to that of Taxol. NAMFIS (NMR
      analysis of molecular flexibility in solution) deconvolution of the averaged 2-D
      NMR spectra for 9a yields seven conformations. Within the latter set, the
      hydrophobically collapsed "nonpolar" and "polar" classes are represented by one
      conformation each with predicted populations of 12-15%. The five remaining
      conformers, however, are extended, two of which correspond to the T-conformation
      (47% of the total population). The latter superimpose well with the recently
      proposed T-Taxol binding conformer in beta-tubulin. The results provide evidence
      for the existence of two previously unrecognized structural features that support
      Taxol-like activity: (1) a reduced torsion angle between C2' and C3' and (2) an
      orthogonal arrangement of the mean plane through C1', C2' and the 2'-hydroxyl and
      the 3'-phenyl plane, the latter ring bisected by the former plane. By contrast,
      epimerization at 2',3' and homologation of the tether to CH2-CH2 were both
      detrimental for activity. The decreased activity of these analogues is apparently
      due to configurational and steric factors, respectively.

PMID- 11334568
TI  - Synthesis and biological evaluation of pyrrolinic isosteres of rilmenidine.
      Discovery of cis-/trans-dicyclopropylmethyl-(4,5-dimethyl-4,5-dihydro-3H-pyrrol-2
      yl)-amine (LNP 509), an I1 imidazoline receptor selective ligand with hypotensive
      activity.
AB  - To find new compounds selective for purported I1 imidazoline receptors (I1Rs)
      over I2 imidazoline binding sites (I2BS) and alpha2-adrenoceptors (alpha2ARs), a
      series of pyrrolinic isosteres of rilmenidine has been prepared and their
      biological activity at I1Rs, I2BS, and alpha2ARs evaluated. This isosteric
      replacement provided us with compounds which still bound to I1Rs but not to I2BS
      nor to alpha2ARs. A limited structure-affinity relationship was generated around
      the heterocyclic moiety of these ligands. One compound in this series, LNP 509
      (1e) [cis-/trans-dicyclopropylmethyl-(4,5-dimethyl-4,5-dihydro-3H-pyrrol-2-yl)
      amine], had no detectable affinity at alpha2ARs yet was capable of lowering blood
      pressure after central administration. These pyrrolinic analogues constitute a
      new chemical class of imidazoline related compounds with high selectivity for the
      I1Rs. They could be used as new tools in the study of I1Rs and in the conception
      of new centrally acting hypotensive drugs.

PMID- 11334569
TI  - Synthesis and biological evaluation of novel A-ring modified hexacyclic
      camptothecin analogues.
AB  - Eleven A-ring modified hexacyclic analogues of camptothecin (CPT) containing a
      1,4-oxazine ring were synthesized from 10-hydroxycamptothecin (11a) and 7-ethyl
      10-hydroxycamptothecin (3) (SN-38) in four to five steps and were subjected to
      the biological tests such as cytotoxicity, topoisomerase I (Topo I) inhibitory
      activity, acetylcholinesterase (AChE) inhibition, and stability in human plasma.
      Four compounds 15a, 15b, 16a, and 16c were about 2-fold more potent than
      topotecan and as potent as CPT toward human cancer cell lines A549, H128, WiDr,
      MKN45, SK-OV-3, and SK-BR-3 in vitro, even though the most active compound 15b
      was slightly less potent than SN-38. The potency of Topo I inhibition of these
      compounds showed relatively good correlation with their cytotoxicity. Most of the
      compounds exhibited AChE inhibitory activity weaker (9 +/- 2 to 20 +/- 3%) than
      CPT (23 +/- 5%) or topotecan (20 +/- 4%) and similar to SN-38 (13 +/- 2%),
      indicating that they might have little effect on causing early diarrhea. The
      stability of lactone forms of these compounds in human plasma seemed to be much
      higher than that of CPT and similar to that of topotecan but lower than that of
      SN-38. Among the new hexacyclic CPT analogues, compound 15b showed higher
      antitumor activity against human tumor xenograft, WiDr, in nude mice compared to
      that of SN-38. The most promising compound 15b has been selected for further
      development.

PMID- 11334570
TI  - 3-(4-Fluoropiperidin-3-yl)-2-phenylindoles as high affinity, selective, and
      orally bioavailable h5-HT(2A) receptor antagonists.
AB  - The development of very high affinity, selective, and bioavailable h5-HT(2A)
      receptor antagonists is described. By investigation of the optimal position for
      the basic nitrogen in a series of 2-phenyl-3-piperidylindoles, it was found that
      with the basic nitrogen at the 3-position of the piperidine it was not necessary
      to further substitute the piperidine in order to obtain good binding at h5-HT(2A)
      receptors. This meant the compounds no longer had high affinity at the IKr
      potassium channel, an issue with previous series of 2-aryl-3-(4
      piperidyl)indoles. Improvements could be made to oral bioavailability in this
      series by reduction of the pK(a) of the basic nitrogen, by adding a fluorine atom
      to the piperidine ring, leading to 3-(4-fluoropiperidin-3-yl)-2-phenyl-1H-indole
      (17). Metabolic studies with this compound identified oxidation at the 6-position
      of the indole as a major route in vitro and in vivo in rats. Blocking this
      position with a fluorine atom led to 6-fluoro-3-(4-fluoropiperidin-3-yl)-2-phenyl
      1H-indole (22), an antagonist with 0.06 nM affinity for h5-HT(2A) receptors, with
      bioavailability of 80% and half-life of 12 h in rats.

PMID- 11334571
TI  - Pharmacological and behavioral analysis of the effects of some bivalent ligand
      based monoamine reuptake inhibitors.
AB  - Novel piperidine-based bivalent ligands were prepared in enantiomerically pure
      form and evaluated for their ability to inhibit reuptake of dopamine (DA),
      serotonin (5-HT), and norepinephrine (NE) into rat brain nerve endings
      (synaptosomes). In this study, we have succeeded in using (1) the length of the
      linking chain connecting the two piperidine-based monomer units and (2) the
      absolute configuration of the piperidine monomer as a means to tailor activity
      and selectivity at the three monoamine transporters tested. In this series, the
      bivalent ligand 16, comprised of two (+)-trans-piperidine units linked by a
      pentamethylene spacer, exhibits a combination of high DA transporter (DAT) and 5
      HT transporter (SERT) activity (K(i) = 39 nM and 7 nM, respectively). Piperidine
      16 is capable of reducing cocaine's locomotor effects in mice while not having
      any effect on locomotion when tested alone. Additionally, compound 16 (1-10
      mg/kg) does not substitute for cocaine in drug discrimination studies in rats.
      However, the analogous bivalent ligand 15 comprised of two (-)-trans-piperidine
      units, which is SERT selective, was less effective in antagonizing cocaine's
      locomotor stimulant activity. The piperidine-based bivalent inhibitors described
      herein constitute a new class of monoamine reuptake inhibitors that exhibit
      varying levels of monoamine transporter activity and selectivity, and these
      ligands may serve as lead candidates in the discovery of new therapeutics to
      treat a range of neurological disorders including cocaine addiction.

PMID- 11334573
TI  - [Clinical units in the primary care teams of Andalusia].

PMID- 11334572
TI  - Combinatorial lead optimization of a neuropeptide FF antagonist.
AB  - The tripeptide Pro-Gln-Arg-NH2, derivatized at the secondary amino group of the
      proline residue with 5-(dimethylamino)-1-naphthalenesulfonyl (dansyl-PQR-NH2),
      antagonizes the central anti-opioid action of neuropeptide FF in animals after
      systemic administration and, therefore, is a therapeutic lead to treat opiate
      withdrawal. For a combinatorial optimization to improve potency, libraries
      focused on the possible replacement of the proline and glutamine residues of this
      lead compound were obtained by a solid-phase split-and-mix method using coded
      amino acids (excluding cysteine) as building blocks. After screening for
      competitive binding against a radioiodinated neuropeptide FF analogue, 5
      (dimethylamino)-1-naphthalenesulfonyl-Gly-Ser-Arg-NH2 (dansyl-GSR-NH2) has
      emerged as one of the compounds in the library with high affinity to the NPFF
      receptor and even with a moderate increase compared to dansyl-PQR-NH2 in its
      predicted ability to penetrate the central nervous system.

PMID- 11334574
TI  - [Qualitative approach to the attitudes and expectations of doctors during the
      process of computerising primary care].
AB  - OBJECTIVE: To find the attitudes and expectations of doctors during the process
      of computerising primary care (PC). DESIGN: Qualitative investigation through
      discussion groups. PARTICIPANTS: Thirty-one doctors from the two PC regions of
      Gipuzkoa. METHOD: Intentional stratified sampling by regions and by experience in
      using a computer in the consulting-room. Five discussion groups with recording
      and transcription of the contents with prior authorisation and guarantee of
      confidentiality. Qualitative analysis of the notes and transcriptions with the
      help of computer back-up. Validation through sending of results to participants
      and discussion between the authors. RESULTS: Introducing computers into PC
      consulting-rooms had repercussions both on the ordering and contents of the
      information recorded. The effort <<to know what is being done>> was not
      accompanied by subsequent evaluation. Notable deficiencies in management of the
      computerising process were perceived. Computer use created additional symbolic
      effects for both patients and doctors. CONCLUSIONS: Computerising PC is a process
      whose repercussions on medical care are far from neutral and so require rigorous
      discussion and evaluation. Defining step-by-step and measurable objectives,
      transparency in management and the promotion of evaluative research would all
      favour the effective development of projects to computerise PC.

PMID- 11334575
TI  - [Direct costs to primary care of chronic bronchitis. Analysis of a prospective
      study].
AB  - OBJECTIVE: To evaluate the consumption of the direct health resources of primary
      care (PC) in Spain by a cohort of patients with chronic bronchial pathology:
      chronic bronchitis (CB) and chronic obstructive pulmonary disease (COPD). DESIGN:
      Prospective cohort study of patients with CB and COPD monitored in PC in Spain.
      The first 10 adult patients who attended at random each researcher's clinic and
      who were diagnosed as suffering an exacerbation of their chronic bronchial
      pathology were included. Scheduled follow-up visits for a year evaluated the
      cohort's consumption of health resources. Direct health costs were analysed.
      RESULTS: 268 doctors, with 2414 patients, took part. 1510 patients completed the
      12 months follow-up (62.6%). All the patients received pharmacological treatment
      for their pulmonary disease. The most common complementary investigations
      performed were: general blood analysis (1.5 per patient/year), chest x-ray (1.2)
      and ECG (0.9), followed by spirometry (0.5) and arterial gasometry (0.4). Mean
      number of exacerbations per year were 1.9; and admissions, 0.2. Overall cost,
      including tests, medical visits, hospital expenditure and pharmacological
      treatment, was 420,264,000 pesetas for the entire cohort. The direct annual cost
      per patient ran at 278,321 pesetas. The cost caused by patients treated with
      Cefixime on the first exacerbations was 77,365 pesetas less, which was mostly due
      to less hospital expense. CONCLUSIONS: The direct annual cost per patient with CB
      or COPD is high, above the cost of other chronic respiratory pathologies such as
      bronchial asthma. There are notably greater hospital costs for CB and COPD,
      explained by these patients' mean greater age and the non-reversible and
      progressive deterioration of their respiratory function.

PMID- 11334576
TI  - [Usefulness of patients' reports in monitoring rational use of medicines].
AB  - OBJECTIVES: To determine the usefulness of patients' reports in constructing
      indicators of the rational use of medicines and to analyse these reports'
      benefits and limitations in comparison with the medical records. DESIGN: Cross
      sectional multi-centred study. SETTING: Eight primary care health centres.
      PATIENTS: For each centre a randomised sample, stratified by medical list, was
      selected of 125 subjects over 18 who had attended on some occasion the medical
      clinic in the previous 12 months (1000 subjects in all). MEASUREMENTS AND MAIN
      RESULTS: A <<report-type>> questionnaire was designed and distributed (with
      questions referring to objective concrete experiences), in which information was
      gathered on various aspects of the use of medicines. In addition, these data were
      checked against the medical records of the subjects who answered the
      questionnaire. The reply rate was 43.7% for the questionnaire as a whole. It
      fluctuated between 92.0% and 46.0% in different specific items. The age of the
      patient, the number of consultations and suffering a chronic illness all affected
      the level of response to the questionnaire. Nevertheless, the users provided
      between 2 and 5 times more information than the medical record, with moderate-to
      high reliability. Concordance between what was reported and what was recorded
      varied between 72.0% and 82.0%. CONCLUSIONS: The user's report can be useful, as
      a substitute for and as a complement to other sources of information, to
      construct indicators of the rational use of medication from an integrated
      perspective.

PMID- 11334577
TI  - [Evaluation of medical reports received from the second level of care].
AB  - OBJECTIVES: To quantify the monthly inter-clinic rate (MIR), the medical reports
      received, their quality and the period of delay until the first second-level
      consultation. DESIGN: Cross-sectional, descriptive study. SETTING: Rural health
      centre. SAMPLE: 498 first consultations requested of the second level by three
      family medicine lists between June and November 1999. 132 were excluded for
      presenting a criterion of exclusion (consultations within the second level, check
      ups, appointments missed by the patient and consultations that could not be
      recorded), which left a sample size of 366. MEASUREMENTS AND RESULTS: Mean MIR
      was 34 . Ophthalmology (21.9%), gynaecology (15.3%) and traumatology (13.9%) were
      the most commonly requested services. 69 reports (18.8%) were received, leaving
      297 (81.2%) not received. Pneumology (100%) and internal medicine (81.8%)
      services sent through most reports, whereas haematology and rehabilitation (0%)
      sent through least. The mean score on the reports was 8 +/- 2 out of a maximum of
      10. Mean delay was 73 +/- 46 days. CONCLUSION: The monthly inter-clinic rate
      found was within the figures cited in the literature. The percentage of reports
      received was way below what was found in the literature, but their quality was
      good.

PMID- 11334578
TI  - [Is there awareness of pharmaceutical expenditure in the reformed primary care
      system?].
AB  - OBJECTIVE: To evaluate the effectiveness of feeding information on pharmacy back
      to primary care doctors in order to create awareness (knowledge) of
      pharmaceutical expenditure (PE). DESIGN: Retrospective cross-sectional study,
      through personal interview. SETTING: Reformed PC, Sabadell, Barcelona.
      PARTICIPANTS: The 80 PC doctors working with primary care teams. INTERVENTIONS:
      As the personal feed-back on PE, each doctor was asked for the PE generated
      during 1997 and the mean cost of prescriptions to active and pensioner patients.
      The statistical test used was the t test to compare means for paired data, with p
      < 0.05 the required level of significance. RESULTS: Out of the total doctors
      interviewed (80), 71 replies were obtained for the annual PE and 76 for the mean
      cost of prescriptions, for both active and pensioner patients. Significant
      differences were found between the annual PE in reality and doctors' estimates:
      around twelve million pesetas. The differences between the real mean costs of
      prescription and the estimates were also significant. CONCLUSIONS: In view of the
      results, it is concluded that there is no awareness of PE among the doctors in
      the reformed PC in our area. This poses a question over the efficacy of feed-back
      of pharmacy information in order to create this awareness. This information needs
      to be more frequent and richer in content, and to be complemented by other
      measures.

PMID- 11334579
TI  - [Use of levofloxacine in primary care for outbreaks in COPD].
AB  - OBJECTIVE: To find scientific evidence to support the indication for treating
      outbreaks in COPD patients on an out-patient basis with levofloxacine, as against
      conventional treatments. DESIGN: Standardised review, following the criteria of
      medicine based on the evidence. A bibliographic search of the MEDLINE data base
      from 1966 to June 2000 was the basis for an analysis of the evidence found.
      SETTING: Non-hospital treatment. PATIENTS AND OTHER PARTICIPANTS: COPD patients
      suffering a light outbreak of probable bacterial origin, according to the
      Anthonisen criteria. INTERVENTIONS: The intervention analysed was treatment with
      500 mg/day of levofloxacine taken orally. An attempt was made to compare this
      with conventional treatments such as amoxycillin-clavulanic acid and acetyl
      cefuroxime. The indicators of results analysed were reduction in mortality or in
      the number of hospital admissions. MEASUREMENTS AND MAIN RESULTS: No clinical
      trial was found that compared levofloxacine and amoxycillin-clavulanic acid. Two
      clinical trials were found that compared levofloxacine and acetyl cefuroxime.
      These found no significant differences between the group treated with
      levofloxacine and the group treated with cefuroxime. CONCLUSIONS: No scientific
      evidence demonstrating advantages of levofloxacine treatment over amoxycillin
      clavulanic acid was found, or over acetyl cefuroxime as empirical PC first-choice
      treatment for patients with outbreaks of COPD.

PMID- 11334580
TI  - [Effect on plasma fibrinogen of hypercholesterolaemia treatment with
      pravastatin].
AB  - OBJECTIVE: To determine whether hypercholesterolaemia treatment with pravastatin
      causes modifications in plasma fibrinogen. DESIGN: Descriptive, prospective
      pharmacological intervention study, with two transversal cuts, one at the start
      and one after 6 months pravastatin treatment. SETTING: Health area located in the
      suburbs of Valencia. PATIENTS: Hypercholesterolaemia cases diagnosed de novo and
      treated with pravastatin for 6 months. Sample size was calculated for paired data
      with an alpha error of 0.05 and a beta error of 20%. The fibrinogen difference
      thought relevant was set at 40 mg/dl. Variability was deduced from a mini-sample
      of 15 cases, obtaining a total of 57 patients. Sex, age, height, weight, BMI,
      count, formula, globular sedimentation rate (GSR), glucaemia, total, HDL and LDL
      cholesterol, and triglycerides were recorded. MEASUREMENTS AND MAIN RESULTS: Mean
      age was 55.9, height 161.9 cm and initial weight 73.9 kg (mean BMI 28.1 kg/m(2)).
      After six months pravastatin treatment (10/20 mg/day) we found no significant
      differences in glucaemia, GSR or leukocytes. There were differences in weight,
      that fell by 1.5 kg (0.6 kg/m(2)), systolic pressure (4.3 mmHg) and diastolic
      pressure (2.7 mmHg) on average. We found the following differences for lipids:
      42.3 mg/dl (15.2%) drop in mean total cholesterol, 27 mg/dl (14.5%) in LDL
      cholesterol, and 36.2 mg/dl (21.9%) in triglycerides. We found a mean increase in
      HDL cholesterol of 4.4 mg/dl. There was a mean drop of 43.7 mg/dl (11.9%) in
      fibrinogen. CONCLUSIONS: We found an 11.9% drop of plasma fibrinogen in patients
      with hypercholesterolaemia treated with pravastatin.

PMID- 11334581
TI  - [Cost-benefit analysis in health care].

PMID- 11334582
TI  - [Primary prevention of eating disorders in adolescence: role of the primary care
      specialist].

PMID- 11334583
TI  - [Peer review in scientific journals].

PMID- 11334584
TI  - [Concerning the pharmaceutical industry's financing of post-graduate courses].

PMID- 11334586
TI  - [Unnoticed hypothyroidism and myopathy due to lipid-lowering drugs].

PMID- 11334587
TI  - [Aneurysms of the abdominal aorta in a primary care clinic].

PMID- 11334588
TI  - [Domestic violence].

PMID- 11334589
TI  - [Adverse cutaneous side-effect of codeine administration].

PMID- 11334590
TI  - [The International Conference on Communication and Health of Barcelona 2000. One
      more step in the right direction].

PMID- 11334591
TI  - [Research into communication and health. A Spanish and international perspective
      through bibliometric analysis].
AB  - OBJECTIVES: 1. To find the scientific output on communication and health both in
      Spain and internationally. 2. To compare the two outputs according to the type of
      articles published and the design of the research. DESIGN: Descriptive and
      bibliometric study. MATERIAL: The data bases MEDLINE (1995-2000) and IME (1990
      2000) and the books summarising papers from semFYC Congresses (1995-2000) were
      used. MEASUREMENTS: The number of articles on MEDLINE published and indexed with
      the description <<physician-patient relationships>>, plus a series of subject
      describers that could be included under the heading <<communication and health>>,
      were counted. On the IME and in the semFYC congress summaries the describers
      <<communication, clinical interview, doctor-patient relationship, doctor-sick
      person communication and doctor-patient communication>> were used. The articles
      indexed on MEDLINE-IME were compared for their classification as original
      articles, clinical practice guidelines, review, editorial or letter to the
      editor. Original articles were classified in randomised and non-randomised
      trials, meta-analysis and observation studies. MAIN RESULTS: 6766 articles were
      found on MEDLINE, 42 on the IME (0.046% of the total indexed) and 34 summaries
      from semFYC congresses (1.47% of the total). Among the most commonly studied
      questions were found patients' information and education, professional stress and
      psychological interviews; among the least studied were difficult and aggressive
      patients, negotiation and people accompanying patients. The original articles on
      MEDLINE and IME were 70% and 37%; and review articles, 11% and 44%. 1.4% of
      MEDLINE articles were randomised trials; and 0.08%, meta-analysis. CONCLUSIONS:
      Communication and health research is a young field that still requires
      descriptive studies. There is little scientific output in this area in Spain,
      with few original papers and too many reviews.

PMID- 11334592
TI  - [Personality traits and burnout in family doctors].
AB  - OBJECTIVE: With this research we try to study personality traits that could be
      associated with high punctuation at burnout scales (Maslach Burnout Inventory) in
      primary care physicians. DESIGN: Observational, descriptive, transversal. STUDY
      SETTING: 93 primary care centres in Barcelona-city and the northern province's
      region: Valles Oriental, Valles Occidental, Maresme, Osona, Bages and Bergueda
      (centre sanitary region). METHOD: Individual or collective direct interview to
      528 primary care physicians. Three questionnaires were administrated: a
      sociodemographic item one, the Maslach Burnout Inventory (MBI), and the Cattell
      personality test 16-PF. RESULTS: The 40% of the interviewed physicians had some
      burnout symptoms without any difference between sexes. 12.4% of these showed very
      high burnout levels. Those subjects with burnout criteria punctuated different at
      stability, tension and vigilance traits and anxiety dimension. CONCLUSION: Some
      personality traits like low stability, the tension and the anxiety are associated
      with high punctuation of burnout.

PMID- 11334593
TI  - [Validity and reliability of an instrument to assess the clinical interviews of
      residents in family and community medicine: the GATHA-RES questionnaire].
AB  - OBJECTIVE: To check the validity of content, the internal consistency and the
      intra-observer reliability of a questionnaire to evaluate the doctor-patient
      communication of family medicine residents. DESIGN: Observation study, to
      validate a measurement instrument. SETTING: Primary care. Family and community
      medicine teaching units. STUDY POPULATION: For the validity analysis: 25 family
      and community medicine residents. For the reliability analysis: 48 doctors in the
      same speciality. MEASUREMENTS AND INTERVENTIONS: The questionnaire was
      constructed on the basis of a version (GATHA-BASE) composed of 42 items selected
      by a panel of 60 general practitioners. For content validity, 68 clinical
      encounters with simulated patients, video-recorded and evaluated, were used. The
      questionnaire's validity content was studied through a factorial analysis. To
      measure its internal consistency, Cronbach's alpha coefficients were calculated.
      Intra-observer reliability of the GATHA-RES version was evaluated through the
      kappa indexes and the intra-class correlation coefficients. RESULTS: We obtained
      a version of the GATHA-RES with 27 items. The factorial analysis revealed that
      there were 9 factors (<<empathy>>, <<anamnesis>>, <<two-way communication>>,
      <<negotiation>>, <<information>>, <<miscellaneous 1>>, <<miscellaneous 2>> and
      <<patient-focused>>) which showed close correlation with the theoretical and
      formal contents of the original questionnaire (originally grouped in three
      sections: attitudes, communication tasks and skills). All the intraclass
      correlation coefficients had figures > or = 0.90. CONCLUSIONS: The GATHA-RES
      questionnaire is a valid and reliable instrument that can be used for evaluating
      the communication skills of general practitioners in training.

PMID- 11334594
TI  - [Pre-hospital care in acute coronary syndromes. Experience of the ARIAM group].
AB  - OBJECTIVE: The advance in the treatment of the acute coronary syndromes tries to
      configure an integral attendance, not only of accelerating the fibrinolytic
      therapy. The objective of the present work is to evaluate basic measures of the
      patients' out of hospital attendance with acute coronary syndromes. DESIGN:
      Descriptive study. SETTING: Hospital center. PATIENTS: Diagnosed patients of
      myocardial infarction or unstable angina derived to intensive care units of 70
      hospitals (ARIAM registry). The patients are classified depending on their
      previous coronary antecedents and to the system that you/they go first. The
      attention is evaluated by means of an specific score, with special attention in
      basic measures: administration of acetylsalicylic acid and nitroglycerin and
      realization of ECG. MEASUREMENTS AND MAIN RESULTS: Among 30746 patients, of those
      that 70.4% was myocardial infarction and 29.6% unstable angina, with 3:1 of
      relationship male/female, the half score of out of hospital attention reaches 1
      point. 48.5% goes for its means, making it the rest for devices of urgent
      attention. It was administered nitroglycerin to 36.7% and acetylsalicylic acid to
      13.1%. Among the patients with antecedents, these proportions remain. Among the
      devices the presence of antecedents seems neither to determine a different
      attitude. The temporal evolution has not suffered spectacular changes and the
      tendency to the observed rise, they are more marked for the less established
      measures. CONCLUSIONS: Inside the evaluation of the out of hospital attendance to
      the acute coronary syndromes exist numerous opportunities of improvement that it
      is necessary to develop to several fronts and where all the sanitary services
      involved will be implied.

PMID- 11334595
TI  - [Prevalence of depression in patients over 65 years of age. Profile of the
      elderly at risk].
AB  - OBJECTIVES: To calculate the prevalence of emotional disorders in primary care,
      using a screening test--the Yesavage--and the association of emotional disorders
      with other variables, with the aim of identifying the profile of an elderly
      person most likely to be depressed at some juncture of his/her life. DESIGN:
      Cross-sectional, descriptive study. SETTING: Urban health care. PATIENTS AND
      OTHER PARTICIPANTS: Sample of 173 patients over 64 years old. MEASUREMENTS AND
      RESULTS: An integrated geriatric assessment was conducted. The complete version
      of the Yesavage scale was used (30 items). 16% prevalence of depression (score
      over 15) was established. The following variables were associated with depression
      in a statistically significant way: feminine sex (p = 0.000009), age > or = 75 (p
      = 0.04), illiteracy or completion of only primary education (p = 0.01),
      dependence in one or more activities of daily life according to the Katz index (p
      = 0.0000006), personal history of depression (p = 0.01), current treatment for
      depression (p = 0.0002), daily consumption of three or more drugs (p = 0.0009)
      and social isolation (p = 0.00006). Multivariate analysis revealed that low
      educational level (p = 0.006), dependence in one or more activities of daily life
      (p = 0.008) and social isolation (p = 0.0008) are the variables most associated
      with depression. CONCLUSIONS: The association between low educational level and
      depression may be due to difficulty in understanding certain questions. A
      therapeutic intervention into established undiagnosed depressions took place. The
      Yesavage geriatric scale was useful in primary care for identifying undetected
      cases of emotional disorder.

PMID- 11334596
TI  - [Referral to endocrinology because of thyroid pathology. Quality and
      justification].
AB  - OBJECTIVES: To describe the content of the form for referring patients to
      endocrinology because of thyroid pathology, to compare this form with the
      specialist report and to analyse the justification for the referral and its
      association with its origin. DESIGN: Descriptive. SETTING: Primary/specialist
      care. PARTICIPANTS: All the patients (412) referred to 4 endocrinology clinics
      for undefined thyroid pathology. RESULTS: 81% of the 273 cases without history on
      the form had this history in the report. The symptoms were recorded more often in
      the report than on the form except for local compression (23 cases, of which the
      endocrinologist confirmed 5). 59.3% of the forms included the analysis results,
      and 31% the physical examination of the thyroid. Consistency, size and nodularity
      of the goitre were only indicated in a minority of forms. Diagnostic concordance
      was low (kappa = 31%). 15.2% were cases of simple goitre. Cases whose referral
      according to an established protocol was justified amounted to 51% when the
      reason was taken into account, and 39% when the diagnosis was taken into account.
      These figures bore no relation to the zone or centre originating the referral.
      Most patients, including those whose referral was not necessary, had further
      tests (PAAF, echography, gammagraphy). CONCLUSIONS: Compliance with the form is
      insufficient, although it is difficult to decide if this implies incorrect
      handling of the patient. Physical examination of the thyroid needs to be
      improved. The referral of many patients is not justifiable, although the
      pathology that predominates is one that may pose diagnostic difficulties without
      the specific examinations that are in fact requested in the specialist clinics.

PMID- 11334597
TI  - [Evaluation of continuous education: from the satisfaction to the impact. With
      regard to a formative programme in minor surgery in a health area].
AB  - OBJECTIVE: To compare the evaluation of reaction of an activity of continuous
      education (CE) in minor surgery (MS), with the impact in the realization of MS in
      a health area. DESIGN: Observational cross-sectional study. Setting. 27 centers
      in a health area that offer MS between their services. MEASUREMENTS: The
      valuation was studied in a scale from 1 to 10, of 9 theoretical-practical
      activities of CE in MS and the consideration of its utility. The number of
      activities of MS (NMS) carried out in all the units, was picked up during one
      year, and a model of lineal regression was built. The independent variable was
      the NMS, and the explanatory ones the assistance pressure (AP), the postgraduate
      formation (PF), the staff of the unit, the equipment (E), and the carried out CE.
      RESULTS: The valuation of the CE had a median of 8 (with interquartile range 1),
      85.1% of the people who realized CE in MS said that this would be of utility.
      However in the explanatory regression model the PF was the only significant
      variable (beta = 6.7; 95% CI, 0.12-12.22). Neither the CE, nor the AP, nor the E,
      explained the variability among the NMS. CONCLUSION: The CE in MS with
      conventional methodology has a very positive reaction evaluation, but its impact
      in the later realization of MS is not significant.

PMID- 11334598
TI  - [A training program in clinical interview techniques: the COMCORD project].

PMID- 11334599
TI  - [Communication, burnout and clinical results: more questions than answers].

PMID- 11334600
TI  - [Brief family psychotherapy. How to facilitate therapy compliance through patient
      cooperation].

PMID- 11334601
TI  - [Appropriate sample for the evaluation of a diagnostic test?].

PMID- 11334603
TI  - [Comments to underevaluation of the ADA criteria with respect to the prevalence
      of diabetes in a high-risk Spanish population].

PMID- 11334605
TI  - [The future of the teaching structure of the specialty of family and community
      medicine].

PMID- 11334607
TI  - [Research and advertisement. Differences in the effectiveness of alendronate
      according to risk groups].

PMID- 11334609
TI  - Prader-Willi syndrome and polygonosomal abnormalities in males:about a Prader
      Willi/47,XYY patient.
AB  - We herein report a male patient known as having a XYY karyotype. At the age of 26
      years a Prader-Willi syndrome (PWS) was diagnosed. Before that time the whole
      symptomatology was ascribed to the XYY syndrome. This is the first reported
      association of PWS and polygonosomal abnormality in a male adult (whose height is
      above average).

PMID- 11334610
TI  - A case of ambiguous genitalia presenting with a
      45,X/46,Xr(Y)(p11.2;q11.23)/47,X,idic(Y)(p11.2),idic(Y)(p11.2) karyotype.
AB  - An infant with ambiguous genitalia was found to have a karyotype
      45,X/46,X,r(Y)(p11.2;q11.23)/47,X,idic(Y)(p11.2),idic(Y)(p11.2) using G-banding,
      C-banding and FISH. Examination of the genitalia revealed a phallus measuring 1.5
      cm in length and 0.5 cm wide with perineal orifice. Subtle phenotypic features
      consistent with Turner syndrome were not present. Genital ultrasonography
      revealed the presence of an infantile uterus. Endoscopy of the vagina, uterus and
      cervix appeared normal.

PMID- 11334611
TI  - Complex chromosome abnormality mimicking t(8;21)in an acute myeloblastic
      leukemia.
AB  - A patient with acute myeloblastic leukemia (AML) and karyotypic abnormality
      mimicking t(8;21) is reported. Because of the uncommon morphology of blasts for
      AML with t(8;21), and absence of AML1-ETO fusion in the RT-PCR analysis,
      fluorescence in situ hybridization (FISH) was applied to precise the abnormality.
      FISH revealed a complex rearrangement involving chromosomes 7, 21 and 8, and
      involvement of the AML1 gene without evidence of AML1-ETO fusion. This case of
      unusual AML illustrates the necessity of collecting all hematologic, cytogenetic,
      and eventual FISH and RT-PCR data to analyse genetic rearrangements in leukemic
      patients.

PMID- 11334612
TI  - Microdissection and reverse painting reveals a microdeletion 6(q26qter) in a de
      novo r(6) chromosome.
AB  - Ring chromosomes 6 are rare constitutional abnormalities with inconsistent
      phenotypic and clinical features. One of the reasons for this variability is the
      cytogenetically undetectable loss of chromosomal material from the telomeric
      segments at 6p or 6q. We have therefore used fluorescence in situ hybridization
      (FISH) to analyse a ring chromosome 6 that was detected in a newborn boy with
      dysmorphic features. Reverse painting of the microdissected ring chromosome onto
      normal metaphase spreads revealed a small deletion of the terminal region of the
      long arm, 6(q26qter). Moreover, the simple all-telomeric sequence (TTAGG)n was
      lost, whereas the p-specific subtelomeric sequence was still present. Our
      findings confirm that microdeletions occur during the formation of r(6)
      chromosomes and, therefore, are an important determinator of the associated
      phenotype.

PMID- 11334613
TI  - On the symmetry of limb deficiencies among children with multiple congenital
      anomalies.
AB  - In humans, unpaired organs are placed in a highly ordered pattern along the left
      right axis. As indicated by animal studies, a cascade of signaling molecules
      establish left-right asymmetry in the developing embryo. Some of the same genes
      are involved also in limb patterning. To provide a better insight into the
      connection between these processes in humans, we analysed the symmetry of limb
      deficiencies among infants with multiple congenital anomalies. The study was
      based on data collected by the International Clearinghouse for Birth Defects
      Monitoring Systems (ICBDMS). Registries of the ICBDMS provided information on
      infants who, in addition to a limb deficiency, also had at least one major
      congenital anomaly in other organ systems. We reviewed 815 such cases of which
      149 cases (18.3 %) were syndromic and 666 (81.7 %) were nonsyndromic. The
      comparisons were made within the associated limb deficiencies, considering the
      information on symmetry, using a comparison group with malformations associated
      not involved in the index association. Among the non-syndromic cases, the left
      right distribution of limb deficiencies did not differ appreciably between limb
      deficiency subtypes (e.g., preaxial, transverse, longitudinal). The left-right
      distribution of limb anomalies did not differ among most types of non-limb
      anomalies, though a predominance of left-sided limb deficiencies was observed in
      the presence of severe genital defects - odds ratio [OR], 2.6; 95 % CI, 1.1-6.4).
      Limb deficiencies (LDs) were more often unilateral than bilateral when
      accompanied by gastroschisis (OR, 0.1) or axial skeletal defects (OR, 0.5). On
      the contrary, LDs were more often bilateral than unilateral when associated with
      cleft lip with or without cleft palate (OR, 3.9) or micrognathia (OR, 2.6).
      Specifically, we found an association between bilateral preaxial deficiencies and
      cleft lip, bilateral amelia with gastroschisis and urinary tract anomalies, and
      bilateral transverse deficiencies and gastroschisis and axial skeleton defects.
      Of 149 syndromic cases, 62 (41.6 %) were diagnosed as trisomy 18. Out of the 30
      cases of trisomy 18 with known laterality, 20 cases were bilateral. In the
      remainder the right and left sides were equally affected. Also, in most cases
      (74.4 %) only the upper limbs were involved. In conclusion the left-right
      distribution of limb deficiencies among some non-limb anomalies may suggest a
      relationship between the development of the limb and the left-right axis of the
      embryo.

PMID- 11334614
TI  - Lipoprotein lipase (LPL) deficiency: a new patient homozygote for the
      preponderant mutation Gly188Glu in the human LPL gene and review of reported
      mutations: 75 % are clustered in exons 5 and 6.
AB  - We have investigated the lipoprotein lipase (LPL) gene of a 2-year-old patient
      presenting classical features of the familial LPL deficiency including
      undetectable LPL activity. DNA sequence analysis of exon 5 identified the patient
      as a homozygote for the Gly188Glu mutation, frequently involved in this disease.
      A review of cases of LPL deficiency with molecular study of the LPL gene showed a
      total number of 221 reported mutations involved in this disease. Gly188Glu was
      involved in 23.5 % of cases and 74.6 % of mutations were clustered in exons 5 and
      6. Based on these observations, we propose a method of screening for mutations in
      this gene.

PMID- 11334615
TI  - Joint effect of G1691A factor V point mutation and factor VII Arg/Gln(353) gene
      polymorphism on the risk of premature coronary artery disease.
AB  - The study sought an association between the G1691A factor V point mutation and
      factor VII Arg/Gln(353) gene polymorphism and premature coronary artery disease
      (CAD), and the interactive effect on CAD risk between the G1691A factor V point
      mutation and factor VII Arg/Gln(353) gene polymorphism as well as between tested
      polymorphisms and traditional risk factors. 167 patients with CAD younger than 55
      years were compared with 132 healthy subjects. The frequency of factor V point
      mutation was 7.8 % among Slovene patients with premature CAD, and 4.5 % among
      controls. No association was found between either the factor V point mutation (AG
      genotype) or M1M1 genotype of factor VII Arg/Gln(353) gene polymorphism and the
      risk of CAD in Slovenia using univariate analysis (factor V point mutation: OR =
      1.8, 95% CI = 0.7-4.9; p = 0.25; factor VII Arg/Gln(353) gene polymorphism: OR =
      1, 95 % CI = 0.6-1.7; p = 0.9). However, a joint effect on the risk of CAD was
      found between factor V point mutation (AG genotype) and M1M1 genotype (OR = 3.6,
      95 % CI = 1-12.9; p = 0.03). Additionally, an interactive effect on CAD risk was
      found between AG genotype and metabolic risk factors (OR = 3.8, 95% CI = 1.1
      13.6; p = 0.03). In conclusion, we provide evidence for a joint effect on CAD
      risk between G1691A factor V point mutation and factor VII Arg/Gln(353) gene
      polymorphism as well as between factor V point mutation and metabolic risk
      factors.

PMID- 11334616
TI  - Mosaic unbalanced structural abnormalities confirmed using FISH on buccal mucosal
      cells.
AB  - Three rare mosaic unbalanced structural rearrangements found in routine
      peripheral blood analysis were confirmed in buccal mucosal cells using interphase
      FISH. Case 1 had a de novo mosaic triplication for 13q22q33 found in 22.5 %
      lymphocytes. D13S585 probe that maps to 13q32q33 confirmed the mosaicism in 41 %
      of buccal mucosal cells. Case 2 had additional material on a 3q derived from
      14q31qter in 83 % of lymphocytes. The 14q-subtelomeric probe was used on buccal
      smear cells: 86 % had three signals and 14 % had two signals. Case 3 was a mosaic
      de novo add(5) in 32 % lymphocytes. The additional material was from 3p26pter.
      The 3p-subtelomere probe confirmed the mosaicism in 40 % buccal epithelial cells.
      This study shows the applicability of interphase FISH to confirm mosaic
      unbalanced rearrangements in a second tissue such as buccal mucosal cells.

PMID- 11334617
TI  - Origin of uniparental disomy 6: presentation of a new case and review on the
      literature.
AB  - Paternal uniparental disomy (UPD) of chromosome 6 has been reported several times
      in patients with (transient) neonatal diabetes mellitus ((T)NDM). Here we present
      our short tandem repeat typing results in a new patient with NDM, revealing a
      paternal isodisomy (UPiD). Summarising these data with those published previously
      on complete paternal (n=13) and maternal (n=2) UPD6, all cases show isodisomy. In
      general, several modes of UPD formation have been suggested: While a meiotic
      origin of UPD mainly results in a uniparental heterodisomy (UPhD), UPiD is
      probably the result of a post-zygotic mitotic error. This mode of formation
      consists of a mitotic nondisjunction in a disomic zygote, followed by either a
      trisomic rescue or a reduplication. Endoduplication in a monosomic zygote is
      another possible but less probable mechanism, taking into consideration that
      monosomic zygotes are not viable. The exclusive finding of isodisomy in case of
      chromosome 6 therefore gives strong evidence that segregational errors of this
      chromosome are mainly influenced by postzygotic factors. This hypothesis is
      supported by the observation of two cases with partial paternal UPiD6 originating
      from mitotic recombination events. The influence of mitotic segregational errors
      in UPD6 formation is in agreement with the results in trisomy/UPD of other
      chromosomes of the C group (7 and 8), and is in remarkable contrast to the
      findings in studies on the origin of the frequent aneuploidies. Multiple factors
      ensure normal segregation and we speculate that they vary in importance for each
      chromosome.

PMID- 11334618
TI  - The clinical phenotype in institutionalised adult males with X-linked mental
      retardation (XLMR).
AB  - In an institutionalised population of 471 mentally retarded adult residents (436
      males and 35 females), 22 males (i.e. 5 % of the male population) had XLMR,
      accounting for 36.1 % of the residents diagnosed with a monogenic disorder (n =
      61). Fragile X syndrome (FRAXA) was diagnosed in 16 residents, X-linked mental
      retardation with marfanoid habitus (Lujan-Fryns syndrome) in 2, and non-specific
      X-linked mental retardation (MRX) in 4 males. The 4 MRX-patients included 3 male
      sibs of a family, carrying a mutation in the IL-1 receptor accessory protein-like
      gene, and one male patient member of the MRX-44 family (linkage with LOD-score of
      2.90). In the group of 215 males with idiopathic mental retardation (MR), family
      histories and pedigree data were compatible with XLMR in 35 males (35/215 = 16.3
      %) from 32 families. Of these 35 males, 5.7 % were microcephalic with dysmorphic
      features and 5.7 % macrocephalic; micro-orchidism and macro-orchidism were each
      found in 11.4 %. One macrocephalic male had also macro-orchidism and dysmorphic
      features. In this study, the diagnosis of XLMR could thus be proposed in 57 males
      i.e. 13.1 % of the total male population. The clinical phenotype, behavioural
      problems and follow-up data in these different subgroups of XLMR are presented.

PMID- 11334619
TI  - Amino acid distributions in integral membrane protein structures.
AB  - Advances in structure determination of membrane proteins enable analysis of the
      propensities of amino acids in extramembrane versus transmembrane locations to be
      performed on the basis of structure rather than of sequence and predicted
      topology. Using 29 available structures of integral membrane proteins with
      resolutions better than 4 A the distributions of amino acids in the transmembrane
      domains were calculated. The results were compared to analysis based on just the
      sequences of the same transmembrane alpha-helices and significant differences
      were found. The distribution of residues between transmembrane alpha-helices and
      beta-strands was also compared. Large hydrophobic (Phe, Leu, Ile, Val) residues
      showed a clear preference for the protein surfaces facing the lipids for beta
      barrels, but in alpha-helical proteins no such preference was seen, with these
      residues equally distributed between the interior and the surface of the protein.
      A notable exception to this was alanine, which showed a slight preference for the
      interior of alpha-helical membrane proteins. Aromatic residues were found to
      follow saddle-like distributions preferring to be located in the lipid/water
      interfaces. The resultant 'aromatic belts' were spaced more closely for beta
      barrel than for alpha-helical membrane proteins. Charged residues could be shown
      to generally avoid surfaces facing the bilayer although they were found to occur
      frequently in the transmembrane region of beta-barrels. Indeed detailed
      comparison between alpha-helical and beta-barrel proteins showed many qualitative
      differences in residue distributions. This suggests that there may be subtle
      differences in the factors stabilising beta-barrels in bacterial outer membranes
      and alpha-helix bundles in all other membranes.

PMID- 11334620
TI  - Involvement of transporter recruitment as well as gene expression in the
      substrate-induced adaptive regulation of amino acid transport system A.
AB  - We investigated the molecular mechanism involved in the adaptive regulation of
      the amino acid transport system A, a process in which amino acid starvation
      induces the transport activity. These studies were done with rat C6 glioma cells.
      System A activity in these cells is mediated exclusively by the system A subtype,
      amino acid transporter A2 (ATA2). The other two known system A subtypes, ATA1 and
      ATA3, are not expressed in these cells. Exposure of these cells to an amino acid
      free medium induces system A activity. This process consists of an acute phase
      and a chronic phase. Laser-scanning confocal microscopic immunolocalization of
      ATA2 reveals that the acute phase is associated with recruitment of preformed
      ATA2 from an intracellular pool to the plasma membrane. In contrast, the chronic
      phase is associated with an induction of ata2 gene expression as evidenced from
      the increase in the steady-state levels of ATA2 mRNA, restoration of the
      intracellular pool of ATA2 protein, and blockade of the induction by
      cycloheximide and actinomycin D. The increase in system A activity induced by
      amino acid starvation is blocked specifically by system A substrates, including
      the non-metabolizable alpha-(methylamino)isobutyric acid.

PMID- 11334621
TI  - Interaction of N-myristoyldimyristoylphosphatidylethanolamine with
      dimyristoylphosphatidylcholine investigated by differential scanning calorimetry:
      binary phase diagram.
AB  - The temperature-composition phase diagram was derived for hydrated, binary
      mixtures of N-myristoyldimyristoylphosphatidylethanolamine (N-14 DMPE) and
      dimyristoylphosphatidylcholine by high sensitivity differential scanning
      calorimetry. Gel phase immiscibility was detected in mixtures containing up to 20
      mol% N-14 DMPE and there was no evidence for compound formation between the two
      components. In the fluid phase nearly complete miscibility is indicated by the
      calorimetric data. These results are relevant to understanding the role of N
      acylphosphatidylethanolamines in the stress combating responses of organisms and
      in their application to developing liposome-based drug delivery systems.

PMID- 11334622
TI  - Phospholipid-cationic lipid interactions: influences on membrane and vesicle
      properties.
AB  - Liposomes composed of synthetic dialkyl cationic lipids and zwitterionic
      phospholipids such as dioleoylphosphatidylethanolamine have been studied
      extensively as vehicles for gene delivery, but the broader potentials of these
      cationic liposomes for drug delivery have not. An understanding of phospholipid
      cationic lipid interactions is essential for rational development of this
      potential. We evaluated the effect of the cationic lipid DOTAP (N-[1-(2,3
      dioleoyloxy)propyl]-N,N,N-trimethylammonium) on liposome physical properties such
      as size and membrane domain structure. DSC (differential scanning calorimetry)
      showed progressive decrease and broadening of the phase transition temperature of
      dipalmitoylphosphatidylcholine (DPPC) with increasing fraction of DOTAP, in the
      range of 0.4-20 mol%. Laurdan (6-dodecanolyldimethylamino-naphthalene), a
      fluorescent probe of membrane domain structure, showed that DOTAP and DPPC
      remained miscible at all ratios tested. DOTAP reduced the size of spontaneously
      forming PC-containing liposomes, regardless of the acyl chain length and degree
      of saturation. The anionic lipid DOPG (dioleoylphosphatidylglycerol) had similar
      effects on DPPC membrane fluidity and size. However, DOTAP/DOPC (50/50) vesicles
      were taken up avidly by OVCAR-3 human ovarian tumor cells, in contrast to
      DOPG/DOPC (50/50) liposomes. Overall, DOTAP exerts potent effects on bilayer
      physical properties, and may provide advantages for drug delivery.

PMID- 11334623
TI  - Bilayer thickness and lipid interface area in unilamellar extruded 1,2
      diacylphosphatidylcholine liposomes: a small-angle neutron scattering study.
AB  - Small-angle neutron scattering (SANS) experiments have been performed on large
      unilamellar liposomes prepared from 1,2-dilauroylphosphatidylcholine (DLPC), 1,2
      dimyristoyl-phosphatidylcholine (DMPC) and 1,2-distearoylphosphatidylcholine
      (DSPC) in heavy water by extrusion through polycarbonate filters with 500 A
      pores. The neutron scattering intensity I(Q) in the region of scattering vectors
      Q corresponding to 0.0015 A(-2) < or = Q(2) < or = 0.0115 A(-2) was fitted using
      a step function model of bilayer neutron scattering length density and supposing
      that the liposomes are spherical and have a Gaussian distribution of radii. Using
      the lipid volumetric data, and supposing that the thickness of bilayer polar
      region equals to d(H) = 9+/-1 A and the water molecular volume intercalated in
      the bilayer polar region is the same as in the aqueous bulk aqueous phase, the
      steric bilayer thickness d(L), the lipid surface area A(L) and the number of
      water molecules per lipid molecule N intercalated in the bilayer polar region
      were obtained: d(L) = 41.58+/-1.93 A, A(L) = 57.18+/-1.00 A(2) and N = 6.53+/
      1.93 in DLPC at 20 degrees C, d(L) = 44.26+/-1.42 A, A(L) = 60.01+/-0.75 A(2) and
      N = 7.37+/-1.94 in DMPC at 36 degrees C, and d(L) = 49.77+/-1.52 A, A(L) =
      64.78+/-0.46 A(2) and N = 8.67+/-1.97 in DSPC at 60 degrees C. After correcting
      for area thermal expansivity alpha approximately 0.00417 K(-1), the lipid surface
      area shows a decrease with the lipid acyl chain length at 60 degrees C: A(L) =
      67.56+/-1.18 A(2) in DLPC, A(L) = 66.33+/-0.83 A(2) in DMPC and A(L) = 64.78+/
      0.46 A(2) in DSPC. It is also shown that a joint evaluation of SANS and small
      angle X-ray scattering on unilamellar liposomes can be used to obtain the value
      of d(H) and the distance of the lipid phosphate group from the bilayer
      hydrocarbon region d(H1).

PMID- 11334624
TI  - Lumen geometry of ion channels formed by Vibrio cholerae EL Tor cytolysin
      elucidated by nonelectrolyte exclusion.
AB  - Vibrio cholerae EL Tor cytolysin, a water-soluble protein with a molecular mass
      of 63 kDa, forms small pores in target cell membranes. In this communication,
      planar lipid bilayers under voltage clamp conditions were used to investigate the
      geometric properties of the pores. It was established that all cytolysin channels
      were inserted into membranes with the same orientation. Sharp asymmetry in the I
      V curve of fully open cytolysin channels persisting at high electrolyte
      concentrations indicated asymmetry in the geometry of the channel lumen. Using
      the nonelectrolyte exclusion method, evidence was obtained that the cis opening
      of the channel had a larger diameter (< or = 1.9 nm) than the trans opening (< or
      = 1.6 nm). The channel lumen appeared constricted, with a diameter of < or = 1.2
      nm. Cup-shaped lumen geometry was deduced for both channel openings, which
      appeared to be connected to each other via a central narrow part. The latter
      contributed significantly to the total electrical resistance and determined the
      discontinuous character of channel filling with nonelectrolytes. Comparisons of
      the properties of pores formed by cytolysins of two V. cholerae biotypes (EL Tor
      and non-O1) indicated that the two ion channels possessed a similar geometry.

PMID- 11334625
TI  - Analysis of antimicrobial peptide interactions with hybrid bilayer membrane
      systems using surface plasmon resonance.
AB  - The lipid binding behaviour of the antimicrobial peptides magainin 1, melittin
      and the C-terminally truncated analogue of melittin (21Q) was studied with a
      hybrid bilayer membrane system using surface plasmon resonance. In particular,
      the hydrophobic association chip was used which is composed of long chain
      alkanethiol molecules upon which liposomes adsorb spontaneously to create a
      hybrid bilayer membrane surface. Multiple sets of sensorgrams with different
      peptide concentrations were generated. Linearisation analysis and curve fitting
      using numerical integration analysis were performed to derive estimates for the
      association (k(a)) and dissociation (k(d)) rate constants. The results
      demonstrated that magainin 1 preferentially interacted with negatively charged
      dimyristoyl-L-alpha-phosphatidyl-DL-glycerol (DMPG), while melittin interacted
      with both zwitterionic dimyristoyl-L-alpha-phosphatidylcholine and anionic DMPG.
      In contrast, the C-terminally truncated melittin analogue, 21Q, exhibited lower
      binding affinity for both lipids, showing that the positively charged C-terminus
      of melittin greatly influences its membrane binding properties. Furthermore the
      results also demonstrated that these antimicrobial peptides bind to the lipids
      initially via electrostatic interactions which then enhances the subsequent
      hydrophobic binding. The biosensor results were correlated with the conformation
      of the peptides determined by circular dichroism analysis, which indicated that
      high alpha-helicity was associated with high binding affinity. Overall, the
      results demonstrated that biosensor technology provides a new experimental
      approach to the study of peptide-membrane interactions through the rapid
      determination of the binding affinity of bioactive peptides for phospholipids.

PMID- 11334626
TI  - Interaction and structure induction of cell-penetrating peptides in the presence
      of phospholipid vesicles.
AB  - Certain short peptides, which are able to translocate across cell membranes with
      a low lytic activity, can be useful as carriers (vectors) for hydrophilic
      molecules. We have studied three such cell penetrating peptides: pAntp
      ('penetratin'), pIsl and transportan. pAntp and pIsl originate from the third
      helix of homeodomain proteins (Antennapedia and Isl-1, respectively). Transportan
      is a synthetic chimera (galanin and mastoparan). The peptides in the presence of
      various phospholipid vesicles (neutral and charged) and SDS micelles have been
      characterized by spectroscopic methods (fluorescence, EPR and CD). The dynamics
      of pAntp were monitored using an N-terminal spin label. In aqueous solution, the
      CD spectra of the three peptides show secondary structures dominated by random
      coil. With phospholipid vesicles, neutral as well as negatively charged,
      transportan gives up to 60% alpha-helix. pAntp and pIsl bind significantly only
      to negatively charged vesicles with an induction of around 60% beta-sheet-like
      secondary structure. With all three peptides, SDS micelles stabilize a high
      degree of alpha-helical structure. We conclude that the exact nature of any
      secondary structure induced by the membrane model systems is not directly
      correlated with the common transport property of these translocating peptides.

PMID- 11334627
TI  - Protein kinase C-induced phosphorylation modulates the Na(+)-ATPase activity from
      proximal tubules.
AB  - This study describes the modulation of the ouabain-insensitive Na(+)-ATPase
      activity from renal proximal tubule basolateral membranes (BLM) by protein kinase
      C (PKC). Two PKC isoforms were identified in BLM, one of 75 kDa and the other of
      135 kDa. The former correlates with the PKC isoforms described in the literature
      but the latter seems to be a novel isoform, not yet identified. Both PKC isoforms
      of BLM are functional since a protein kinase C activator, TPA, increased the
      total hydroxylamine-resistant 32P(i) incorporation from [gamma-32P]ATP into the
      BLM. In parallel, TPA stimulated the Na(+)-ATPase activity from BLM in a dose
      dependent manner, the effect being reversed by the PKC inhibitor sphingosine. The
      stimulatory effect of TPA on Na(+)-ATPase involved an increase in the V(max)
      (from 13.4+/-0.6 nmol P(i) mg(-1) min(-1) to 25.2+/-1.4 nmol P(i) mg(-1) min(-1),
      in the presence of TPA, P<0.05) but did not change the apparent affinity for
      Na(+) (K(0.5)=14.5+/-2.1 mM in control and 10.0+/-2.1 mM in the presence of TPA,
      P>0.07). PKC involvement was further confirmed by stimulation of the Na(+)-ATPase
      activity by the catalytic subunit of PKC (PKC-M). Finally, the phosphorylation of
      an approx. 100 kDa protein in the BLM (the suggested molecular mass of Na(+)
      ATPase [1]) was induced by TPA. Taken together, these findings indicate that PKCs
      resident in BLM stimulate Na(+)-ATPase activity which could represent an
      important mechanism of regulation of proximal tubule Na(+) reabsorption.

PMID- 11334628
TI  - Influence of plant terpenoids on the permeability of mitochondria and lipid
      bilayers.
AB  - Five sesquiterpene alcohol esters of the carotane series, from plants of the
      genus Ferula, were investigated with regard to their capacity to modify the ion
      permeability of both planar lipid bilayers and mitochondria. These compounds are
      subdivided into two structural groups that differ in their effects on membrane
      permeability. Complex esters of sesquiterpene alcohols with aliphatic acids,
      which constituted the first group (lapidin and lapiferin), do not possess
      ionophoric properties. The second group comprised complex esters of sesquiterpene
      alcohols with aromatic acids (ferutinin, tenuferidin and ferutidin), all of which
      increase cation permeability of lipid bilayers and mitochondria in a dose
      dependent manner. A pronounced selectivity of the terpenoid-modified membranes
      for divalent cations versus monovalent cations was found. Evidence of a carrier
      mechanism for terpenoid-induced ion transport is demonstrated. A tentative
      complex composed of a divalent cation with two molecules of membrane-active
      terpenoid is proposed.

PMID- 11334629
TI  - Molecular cloning and functional expression of Xenopus laevis oocyte ATP
      activated P2X4 channels.
AB  - All cells contain mechanosensitive ion channels, yet the molecular identities of
      most are unknown. The purpose of our study was to determine what encodes the
      Xenopus oocyte's mechanosensitive cation channel. Based on the idea that
      homologues to known channels might contribute to the stretch channels, we
      screened a Xenopus oocyte cDNA library with cation channel probes. Whereas other
      screens were negative, P2X probes identified six isoforms of the P2X4 subtype of
      ATP-gated channels. From RNase protection assays and RT-PCR, we demonstrated that
      Xenopus oocytes express P2X4 mRNA. In expression studies, four isoforms produced
      functional ATP-gated ion channels; however, one, xP2X4c, had a conserved cysteine
      replaced by a tyrosine and failed to give rise to functional channels. By
      changing the tyrosine to a cysteine, we showed that this cysteine was crucial for
      function. We raised antibodies against a Xenopus P2X4 C-terminal peptide to
      investigate xP2X4 protein expression. This affinity purified anti-xP2X4 antibody
      recognized a 56 kDa glycosylated Xenopus P2X4 protein expressed in stably
      transfected HEK-293 cells and in P2X4 cDNA injected oocytes overexpressing the
      cloned P2X4 channels; however, it failed to recognize proteins in control,
      uninjected oocytes. This suggests that P2X4 channels and mechanosensitive cation
      channels are not linked. Instead, oocyte P2X4 mRNA may be part of the stored pool
      of stable maternal mRNA that remains untranslated until later developmental
      stages.

PMID- 11334630
TI  - Effect of trehalose in low concentration on the binding and transport of
      porphyrins in liposome-human serum albumin system.
AB  - The influence of trehalose on the interaction of liposomes with porphyrins and
      with human serum albumin (HSA) was studied. Small unilamellar liposomes were
      prepared from 1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine (DMPC) and from
      DMPC/1,2-dimyristoyl-sn-glycero-3-phosphatidylglycerol (DMPG) 19:1 w/w% and
      incorporated with mesoporphyrin IX (MP) or magnesium mesoporphyrin (MgMP). The
      fluorescence intensity and anisotropy of porphyrins were measured within the
      temperature range of 15-33 degrees C, in the presence and in the absence of 3x10(
      2) M trehalose, to study the location of the porphyrins inside the liposomes and
      their partition between the liposomes and HSA. Based on the presented data and
      our earlier results (I. Bardos-Nagy, R. Galantai, A.D. Kaposi, J. Fidy, Int. J.
      Pharm. 175 (1998) 255-267) we conclude that trehalose - even at this relatively
      low concentration - interacts with the head groups of the liposomes and that the
      presence of DMPG enhances the effect. This effect seems to hinder the binding of
      HSA to the liposome surface and influences the location of MgMP within the
      liposomes. In the case of MP, the porphyrin partition between the liposomes and
      HSA was affected by trehalose, while for MgMP, trehalose changed the structural
      conditions of porphyrin binding to the liposomes. The amount of trehalose used
      did not have a general trend to modify the association constants of porphyrin
      derivatives either to liposomes or to HSA.

PMID- 11334631
TI  - Functional properties of a truncated recombinant GIRK5 potassium channel.
AB  - Xenopus laevis oocytes codify a G-protein-activated inward rectifier potassium
      channel (GIRK5 or Kir3.5). Coinjection of other GIRKs, the muscarinic m2
      receptor, or Gbetagamma protein cRNAs is required to observe functional GIRKx
      GIRK5 heteromultimers in oocytes. Studies with GIRK2 isoforms have shown that the
      size of the amino or carboxyl terminus plays a crucial role on giving functional
      K(+) channels. In this work we studied the properties of a GIRK5 with 25 amino
      acids deleted toward its amino-terminal domain. Injection of GIRK5-Delta25 cRNA
      alone displayed large basal and transient inward rectifying currents in oocytes.
      The instantaneous currents reached a stationary level after a long duration
      voltage pulse (10 s). For this relaxation, fast (tau(1)) and slow (tau(2)) time
      constants were estimated at different voltages. Recovery from inactivation
      followed a monoexponential function (tau=0.95+/-0.07 s). By contrast with other
      inward rectifier channels, blockade of GIRK5-Delta25 by extracellular Ba(2+) was
      voltage-independent (K(d)=102+/-2 microM), suggesting the presence of a Ba(2+)
      site at the external channel vestibule. To confirm this hypothesis, the Ba(2+)
      sensitivity of two charged mutants GIRK5-Delta25(N129E) and GIRK5-Delta25(K157E)
      at each of the external loops was determined. GIRK5-Delta25(N129E) and GIRK5
      Delta25(K157E) showed a 100-fold and 2-fold higher affinity to Ba(2+),
      respectively, supporting the existence of this Ba(2+) binding site.

PMID- 11334632
TI  - Magnetic resonance imaging and cerebral volumic evaluation: comparison of four
      post-processing techniques.
AB  - Four different MRI techniques of volumetric evaluation were applied in 10 healthy
      females and compared. The results have shown that not all techniques were
      interchangeable, but that the results of two groups of methods are not
      statistically different.

PMID- 11334633
TI  - Determination of aorta failure with the application of FFT, AR and wavelet
      methods to Doppler technique.
AB  - In this study, Doppler signals recorded from the output of aorta valve of 24
      patients were transferred to a personal computer (PC) by using a 16-bit sound
      card. Doppler difference frequencies were recorded from each of the patients, and
      then analyzed using fast Fourier transform, autoregressive and wavelet transform
      analyzer to obtain their sonograms. These sonograms are then used to compare with
      the applied methods in terms of medical evaluation.

PMID- 11334634
TI  - Analysis of the imputed female urinary incontinence data for the evaluation of
      expert system parameters.
AB  - We evaluated parameters for an expert system which will be designed to aid the
      differential diagnosis of female urinary incontinence by using knowledge
      discovered from data. To allow the statistical analysis, we applied means,
      regression and Expectation-Maximization (EM) imputation methods to fill in
      missing values. In addition, complete-case analysis was performed. Logistic
      regression results from the imputed data were reasonable. The significant
      parameters were mostly those that are important in the diagnostic work-up.
      Moreover, directions of relations between the parameters and the stress, mixed
      and sensory urge diagnoses were as expected. Analysis with the complete reduced
      data set gave clearly insufficient results. Imputed values had a moderate
      agreement, but odds ratios and classification accuracies of logistic regression
      equations were similar. Results suggest that with these data, simpler methods may
      be used to allow multivariate analysis and knowledge discovery, when better
      methods, such as EM imputation, are unavailable. Cluster analysis detected
      clusters corresponding to the small normal class, but was unable to clearly
      separate the larger incontinence classes.

PMID- 11334635
TI  - ANTHEPROT: an integrated protein sequence analysis software with client/server
      capabilities.
AB  - Programs devoted to the analysis of protein sequences exist either as stand-alone
      programs or as Web servers. However, stand-alone programs can hardly accommodate
      for the analysis that involves comparisons on databanks, which require regular
      updates. Moreover, Web servers cannot be as efficient as stand-alone programs
      when dealing with real-time graphic display. We describe here a stand-alone
      software program called ANTHEPROT, which is intended to perform protein sequence
      analysis with a high integration level and clients/server capabilities. It is an
      interactive program with a graphical user interface that allows handling of
      protein sequence and data in a very interactive and convenient manner. It
      provides many methods and tools, which are integrated into a graphical user
      interface. ANTHEPROT is available for Windows-based systems. It is able to
      connect to a Web server in order to perform large-scale sequence comparison on up
      to-date databanks. ANTHEPROT is freely available to academic users and may be
      downloaded at http://pbil.ibcp.fr/ANTHEPROT.

PMID- 11334636
TI  - Java-based graphical user interface for MRUI, a software package for quantitation
      of in vivo/medical magnetic resonance spectroscopy signals.
AB  - This article describes a Java-based graphical user interface for the magnetic
      resonance user interface (MRUI) quantitation package. This package allows MR
      spectroscopists to easily perform time-domain analysis of in vivo/medical MR
      spectroscopy data. We have found that the Java programming language is very well
      suited for developing highly interactive graphical software applications such as
      the MRUI system. We also have established that MR quantitation algorithms,
      programmed in the past in other languages, can easily be embedded into the Java
      based MRUI by using the Java native interface (JNI).

PMID- 11334642
TI  - The role of the dura in conditioned taste avoidance induced by cooling the area
      postrema of male rats.
AB  - Experiments were designed to assess the contribution of the dura mater to the
      formation of conditioned taste avoidance induced by cooling the area postrema.
      The results of the first experiment verified that the temperature of the dura
      showed a temperature gradient at various distances from the tip of the cold
      probe. In the second and third experiments, a circle of dura was cut away so that
      different amounts of the area postrema could be cooled without cooling the
      overlying dura. Cooling the dura plus the area postrema did not produce a
      stronger avoidance than just cooling the area postrema. In the fourth experiment,
      the cerebellar cortex was cooled with and without cooling the dura. Cooling the
      cerebellar cortex produced conditioned taste avoidance, and cooling the dura plus
      the cerebellar cortex did not produce a stronger avoidance. Taken together, these
      results suggest that cooling the dura mater does not contribute to the
      conditioned taste avoidance induced by cooling the area postrema. The results of
      the fifth experiment showed that cooling the area postrema produced a stronger
      conditioned taste avoidance than cooling the cerebellar cortex. It is suggested
      that the avoidance induced by cooling both of these structures is the result of
      physiological changes occurring when neurons in these structures are inactivated
      and when the subdural meninges are cooled. Furthermore, these changes are more
      severe when the area postrema is cooled.

PMID- 11334643
TI  - Effects of dentate nucleus lesions on spatial and postural sensorimotor learning
      in rats.
AB  - The role of the dentate nucleus on spatial orientation, assessed by the Morris
      water maze test, and on postural sensorimotor performance, assessed by vertical
      grid, suspended wire, and rotorod tests, was investigated. Bilateral electrolytic
      lesions of the dentate nucleus slowed down the acquisition of the hidden platform
      task of the Morris water maze, without affecting long-term retention, the probe
      trial, and the visuomotor guidance necessary for swimming toward a visible goal.
      In addition, reversal learning was impaired in the submerged platform condition.
      The lesions did not affect any of the motor performance scores. The selective
      impairment seen during acquisition of the hidden platform task is similar to that
      previously reported in rats with combined lesions of the cerebellar hemispheres
      and dentate, indicating a specific role for this region in spatial orientation.

PMID- 11334644
TI  - Time-dependent effects of pyramidotomy in the operantly conditioned rats.
AB  - The effect of unilateral transection of bulbar pyramid on operantly conditioning
      in rats, have been shown to be in direct relationship with the time of its
      execution. Stable instrumental reflexes reappeared on average 3.9 days after the
      transection of the bulbar pyramid. However, preliminary transection of the
      pyramid led to the prolongation of stabilization of operant conditioning after an
      average of 16.5 days. These findings are considered to be in view of the
      mechanisms of switching of descending influences of corticospinal and cortico-
      rubrospinal systems.

PMID- 11334645
TI  - Patterns of transfer of adaptation among body segments.
AB  - Two experiments were conducted in order to determine the patterns of transfer of
      visuomotor adaptation between arm and head pointing. An altered gain of display
      of pointing movements was used to induce a conflict between visual and
      somatosensory representations. Two subject groups participated in Experiment 1:
      group 1 adapted shoulder pointing movements, and group 2 adapted wrist pointing
      movements to a 0.5 gain of display. Following the adaptation regimen, subjects
      performed a transfer test in which the shoulder group performed wrist movements
      and the wrist group performed shoulder movements. The results demonstrated that
      both groups displayed typical adaptation curves, initially undershooting the
      target followed by a return to baseline performance. Transfer tests revealed that
      both groups had high transfer of the acquired adaptation to the other joint.
      Experiment 2 followed a similar design except that group 1 adapted head pointing
      movements and group 2 adapted arm pointing movements. The arm adaptation had high
      transfer to head pointing while the head adaptation had very little transfer to
      arm pointing. These results imply that, while the arm segments may share a common
      target representation for goal-directed actions, individual but functionally
      dependent target representations may exist for the control of head and arm
      movements.

PMID- 11334646
TI  - Prior test experience compromises the anxiolytic efficacy of chlordiazepoxide in
      the mouse light/dark exploration test.
AB  - It is now well established that prior test experience can alter behavioural
      baselines and attenuate/abolish the anxiolytic efficacy of benzodiazepines in the
      elevated plus-maze paradigm. In view of evidence that different models of anxiety
      measure qualitatively distinct forms of anxiety-like behaviour, it is important
      to establish whether the effects of prior experience extend to other widely-used
      tests. The present study assessed the behavioural and pharmacological sequelae of
      a single undrugged prior exposure to the light/dark exploration (L/D) test in
      mice, using ethological scoring methods. One group of adult male Swiss-Webster
      mice was given a single undrugged exposure to the L/D test 24 h prior to drug
      testing, while another group was completely naive to the apparatus. On test day,
      half the animals in each experiential condition were treated with saline and half
      with an anxiolytic dose (10 mg/kg) of chlordiazepoxide (CDP). When administered
      to test-naive animals, CDP induced a clear reduction in anxiety-like behaviour as
      evidenced by significant increases in exploration of the light compartment (line
      crossings, % line crossings, and % time) as well as reductions in stretched
      attend postures (SAPs) and the proportion of SAPs displayed toward the light
      compartment. The behavioural specificity of these effects was confirmed by the
      absence of a drug effect on line crossings in the dark compartment, total rearing
      and grooming. In complete contrast, with the sole exception of a decrease in
      total SAPs, CDP was without significant behavioural effect in test-experienced
      mice. As prior test experience did not significantly alter behavioural baselines
      in the L/D test, a second experiment was designed to investigate the possibility
      that handling/intraperitoneal injection may have precluded detection of
      experientially-induced changes in baseline behaviour. Results showed that
      handling/injection had no effect upon L/D behavioural profiles in either test
      naive or test-experienced subjects, and confirmed that prior experience itself
      did not modify the primary indices of anxiety in this test. Present data indicate
      that prior test experience seriously compromises the anxiolytic efficacy of CDP
      (10 mg/kg) in the mouse L/D test and, together with recent findings in the four
      plate test, appear to confirm that an experientially-induced reduction in
      sensitivity to the anxiolytic effects of benzodiazepines is by no means unique to
      the elevated plus-maze.

PMID- 11334647
TI  - Vibrissal sense is not the main sensory modality in rat exploratory behavior in
      the elevated plus-maze.
AB  - Four groups of male Wistar rats were submitted to acute bilateral removal of
      mystacial vibrissae at different lengths from the follicle. Each group was
      divided into two subgroups, tested under high (150 Lux) and low environmental
      illumination (2 Lux). All the subjects were allowed to freely explore an elevated
      plus-maze for 5 min. Results indicated that rats tested under low illumination
      tended to explore the open arms more frequently and longer then rats tested under
      high illumination. When tested under low illumination, rats in the group that
      suffered whole vibrissa removal stayed longer in the open arms than those in the
      other groups but did not differ in the number of entries. The average increase in
      the length of open arm entries, rather than a decrease in aversion to the open
      arms, may be due to the need of more time to obtain information about the
      environment since there is no light and the vibrissae were removed. This effect
      was not seen with rats tested under high illumination, possibly because vision
      could be used to obtain relevant information.

PMID- 11334648
TI  - Differential effect of thalamic and cortical lesions on memory systems in the
      rat.
AB  - The behavioral effects of lesions of anterior thalamic and medio-dorsal thalamic
      nuclei, posterior cingulate (retrosplenial) and posterior parietal associative
      cortex were studied in rats performing a eight-arm radial maze, in which
      three/eight arms were baited. Lesions were made after rats reached a training
      criterion. Rats were tested 2 weeks later, in the same experimental apparatus. In
      the first experiment, performance was assessed by number of errors and time per
      trial, retention by comparing performance during training with retraining
      sessions (using specific scores for reference and working memory) and by an
      evaluation of the 'reminiscence' defined as daily improvement in performance.
      After the reacquisition of the task, the rats were tested in experiment II, in
      modified situations for an evaluation of flexible aspects of memory processing in
      this spatial task. Results showed dissociation between the effects of the
      different lesions, according to the specific demands of the different tasks.
      Posterior parietal lesions produced significant, but relatively mild deficits, in
      all situations, in accordance with the well-established function of this cortical
      region in spatial tasks. In contrast, after cortical lesion in the retrosplenial
      region, performance deficit was only observed on priming and attention to
      contextual change. Lesions of the thalamic associative nuclei also induced task
      specific deficits. Medio-dorsal lesions induced mild and reversible deficits in
      complex tasks only, with preservation of working memory, of priming effect, and
      of a novel acquisition. Rats with anterior thalamic lesions had massive deficits
      across tasks, probably due to basic difficulties with reference and working
      memory, demonstrated no benefit from a priming session but considerable
      interference from the previous training to a new one. These results are discussed
      within framework of the specificity of different cerebral regions for behavioural
      adaptation and plasticity.

PMID- 11334649
TI  - Dopamine mediation of the feeding response to violations of spatial and temporal
      expectancies.
AB  - The present studies were aimed at further characterizing the role of DA in
      motivation. Rats, conditioned to expect food in one environment and no food in
      another, all received food on the test night. Those in the environment in which
      food was unexpected ate four times as much as those eating where food was
      expected. The overeating was eliminated by administration of the D2 antagonist
      raclopride. Another expectancy, timing of light offset in rats entrained to a
      fixed light--dark cycle, was violated by unexpectedly turning the lights off 1 h
      early. This provoked an elevation in food intake, which was also eliminated by
      the administration of raclopride. Feeding in two other situations not involving
      violation of expectancies (food deprivation; normal light offset) was unaffected
      by DA antagonism. These findings support the idea that DA signals errors in
      expectancy and that DA signaling is necessary for certain behavioral responses to
      unexpected events.

PMID- 11334650
TI  - Learning and memory in streptozotocin-induced diabetic rats in a novel
      spatial/object discrimination task.
AB  - Diabetes mellitus is associated with disturbances of cognitive functioning. The
      aim of this study was to examine cognitive functioning in diabetic rats using the
      'Can test', a novel spatial/object learning and memory task, without the use of
      aversive stimuli. Rats were trained to select a single rewarded can from seven
      cans. Mild water deprivation provided the motivation to obtain the reward (0.3 ml
      of water). After 5 days of baseline training, in which the rewarded can was
      marked by its surface and position in an open field, the animals were divided
      into two groups. Diabetes was induced in one group, by an intravenous injection
      of streptozotocin. Retention of baseline training was tested at 2-weekly
      intervals for 10 weeks. Next, two adapted versions of the task were used, with 4
      days of training in each version. The rewarded can was a soft-drink can with
      coloured print. In a 'simple visual task' the soft-drink can was placed among six
      white cans, whereas in a 'complex visual task' it was placed among six soft-drink
      cans from different brands with distinct prints. In diabetic rats the number of
      correct responses was lower and number of reference and working memory errors
      higher than in controls in the various versions of the test. Switches between
      tasks and increases in task complexity accentuated the performance deficits,
      which may reflect an inability of diabetic rats to adapt behavioural strategies
      to the demands of the tasks.

PMID- 11334651
TI  - Cross-modal integration and conceptual categorization in baboons.
AB  - This study investigates concept formation and cross-modal integration in baboons.
      Response times were recorded in a categorical task involving discrimination
      between human and baboon vocalizations. We show that a brief presentation of
      human or baboon prime pictures conceptually related to the target sound shortened
      response speed of one baboon. Cross-modal priming effects were replicated with
      degraded pictures, and were also found in a sample of humans. Cross-modal priming
      demonstrates that this baboon had formed amodal abstract concepts of the human
      and baboon categories.

PMID- 11334652
TI  - Motor discoordination in mutant mice heterozygous for the type 1 inositol 1,4,5
      trisphosphate receptor.
AB  - In the brain, the type 1 inositol 1,4,5-trisphosphate receptor (IP3R1) is a major
      subtype of receptors for inositol 1,4,5-trisphosphate, which mediates the release
      of calcium from intracellular stores. The motor function of knockout mice
      heterozygous for IP3R1 (IP3R1+/-) was assessed. An impairment of motor
      coordination was observed in IP3R1+/- mice in the rotating rod test. There was no
      observable difference between genotypes in spontaneous motor activity, grip
      strength, the hanging test, or walking pattern. These results suggest that IP3R1
      plays a substantial role in motor coordination.

PMID- 11334653
TI  - CAPRICORN: a story of alpha allocation and beta-blockers in left ventricular
      dysfunction post-MI.
AB  - Beta-blocker therapy is beneficial both after myocardial infarction and in mild,
      moderate and severe chronic heart failure. Recent sub-group analysis of the
      Goteborg Metoprolol Trial and the AIRE study confirm that patients receiving beta
      blockers in the setting of post-MI heart failure fare better than patients not
      receiving this therapy. For all these reasons the CAPRICORN trial of carvedilol
      in post-MI LV dysfunction was an important and eagerly awaited trial. The results
      were presented for the first time at The American College of Cardiology on March
      20 2001. CAPRICORN randomised 984 patients to placebo and 975 to carvedilol
      between 3 and 21 days (mean 10) after a confirmed MI. Patients had to have
      evidence of a left ventricular ejection fraction 40% or less. All patients had
      received ACEI therapy for at least 48 hours prior to randomisation. The mean
      ejection fraction of the patients recruited was 32.7% in the placebo group and
      32.9% in the carvedilol group. Follow-up was for a mean of 15 months (maximum 2.7
      years). All cause mortality was 15.3% (151 deaths) in the placebo group and 11.9%
      (116 deaths) in the carvedilol group, giving a hazard ratio of 0.77 (0.60-0.98)
      and a significance of p = 0.031. And yet this agent will probably not be given a
      licence for this indication in the European Union and the USA. The reason is one
      of trial design and statistical declarations. Some way into the trial the
      Steering Committee decided to change the primary end-point form all-cause
      mortality to two co-primary end-points and to allocate their alpha power of 0.05
      unevenly between the combined end-points of all cause mortality and
      cardiovascular hospitalisation (alpha 0.045) and all cause mortality (alpha
      0.005). In the end neither was achieved, one because of the large number of non
      specific hospitalisations for chest pain and the mortality effect because it was
      allocated a punitive and unachievable target of p < 0.005. The trial is thus
      officially neutral despite showing convincing clinical benefit. Clearly arcane
      matters of statistical plans do matter and steering committees should think very
      carefully before changing the primary end-points of major trials.

PMID- 11334654
TI  - Tissue factor/tissue factor pathway inhibitor system and long-term prognosis
      after acute myocardial infarction.
AB  - The tissue factor and tissue factor pathway inhibitor (TFPI) system has been
      studied in the acute phase of coronary disease but its prognostic importance has
      been less well assessed. We evaluated its association with recurrent coronary
      events during long-term follow-up after a myocardial infarction. METHODS: We
      studied 55 consecutive patients with the following criteria for inclusion: (1)
      first myocardial infarct; (2) aged < 70 years; (3) non-complicated infarct; (4)
      low risk effort-test. Blood samples were taken 60-80 days after infarction.
      Tissue factor, total and free-TFPI were measured. A 4-year follow-up was carried
      out. Death, unstable angina and new myocardial infarction were considered as poor
      prognosis. RESULTS: There were no statistical differences in tissue factor/TFPI
      levels between patients and controls. Total-TFPI showed statistical correlation
      with total cholesterol (r = 0.59), triglycerides (r = 0.34), LDL-cholesterol (r =
      40) and Lipoprotein(a) (r = 0.48). Patients with high levels of cholesterol, LDL
      cholesterol and triglycerides showed elevated levels of total-TFPI with no
      differences in free-TFPI. During follow-up, 8 patients showed poor prognosis.
      There were no statistical associations between tissue factor/TFPI levels and
      prognosis. CONCLUSIONS: After acute myocardial infarction, we did not find any
      differences in the tissue factor/TFPI system between controls and patients. The
      tissue factor/TFPI system showed little value as a prognostic factor.

PMID- 11334655
TI  - Assessment of left atrial appendage function and its relationship to pulmonary
      venous flow pattern by transesophageal echocardiography.
AB  - We evaluated left atrial appendage function and its relationship to pulmonary
      venous flow in 53 patients divided into four groups. Group 1 consisted of 10
      normal subjects. Group 2 included 15 patients with significant pure mitral
      stenosis in sinus rhythm. In group 3, there were 13 patients with pure
      significant mitral stenosis and atrial fibrillation. Group 4 consisted of 15
      patients with normal mitral valve and atrial fibrilltion. We found significant
      decrease in left atrial appendage ejection fraction and maximum emptying flow
      velocity, velocity time integral of systolic pulmonary venous flow in Groups 2, 3
      and 4 in comparison with normal subjects. Systolic pulmonary venous flow velocity
      was significantly decreased in Groups 3 and 4. There was significant correlation
      between left atrial appendage ejection fraction and peak emptying flow velocity
      (r = 0.62, P < 0,001). Systolic peak pulmonary venous flow velocity was
      significantly correlated with left atrial appendage ejection fraction and maximum
      emptying flow velocity (r = 0.67, P = 0,01; r = 0.58, P < 0,001, respectively).
      There was also significant correlation between systolic pulmonary venous flow
      velocity time integral and left atrial appendage ejection fraction (r = 0.66, P =
      0.001). When normals were excluded from analysis, all the correlations were still
      significant. We concluded that left atrial appendage is a contractile structure,
      and that systolic pulmonary venous flow velocity is influenced by left atrial
      appendage dysfunction. Therefore left atrial appendage function needs to be
      considered when interpreting Doppler transmitral and systolic pulmonary venous
      flow patterns.

PMID- 11334656
TI  - Inoue balloon mitral valvotomy in patients with atrial septal aneurysm.
AB  - Atrial septal aneurysms (ASA) are not uncommonly detected in patients with
      rheumatic mitral stenosis and pose problems during transeptal puncture in
      patients undergoing balloon mitral valvotomy. From a period of August 1995 to May
      1998, we performed a total of 680 Inoue Balloon Mitral Valvotomy (IBMV)
      procedures with ASA noted in 30 patients, 13 of diffuse and 17 localized type.
      Transesophageal echocardiography (TOE) was used in all patients with suspected
      aneurysm on transthoracic echo (TTE) for exact three-dimensional delineation of
      the location and extent of the aneurysm. The localized type of aneurysms were
      further subcategorized into five types viz. antero-superior and leftwards (6),
      postero-superior and rightwards (2), antero-inferior and leftwards (2), postero
      inferior and rightwards (5), and central (2), depending on their location in the
      atrial septum. The site for transeptal puncture was decided after this
      localization and the remainder of the IBMV procedure was as usual. In the set of
      thirteen patients with diffuse type of atrial septal aneurysms all but one case
      had a successful transeptal puncture using standard technique except for a
      somewhat inferior puncture site so as to be perpendicular to the plane of atrial
      septum and a successful mitral valve dilatation was possible at first attempt. In
      the set of 17 patients with localized type of aneurysms, all had a successful
      transeptal puncture except one. In patients with aneurysms localized antero
      superiorly and leftwards the septal puncture was done in a slightly inferior
      location with transeptal needle pointing some what more posterior, i.e. 5 or 6
      o'clock position and in patients with aneurysms localized postero-inferiorly the
      puncture was done more cephalic with needle directed somewhat anterior, i.e. 3-2
      o'clock position. In the two patients with Atrial septal aneurysms located
      postero-superiorly and to the right the puncture was done slightly inferior but
      with transeptal needle pointing to about 3 or 2 o'clock position and in the
      single patient with antero-inferior location the puncture was done in slightly
      higher but with a more posterior directed needle, i.e. 5-6 o'clock position. The
      two patients with centrally located localized type of aneurysms had successful
      transeptal puncture with standard needle direction (4 o'clock) but at a slightly
      inferior location. We conclude that a good localization of atrial septal
      aneurysms using transesophageal echocardiography and our technique of transeptal
      puncture leads to a successful outcome in majority of cases undergoing Inoue
      balloon mitral valvotomy with associated atrial septal aneurysms.

PMID- 11334657
TI  - The outcome of idiopathic dilated cardiomyopathy and myocarditis in children from
      the west of Scotland.
AB  - We analysed retrospectively all infants and children with idiopathic dilated
      cardiomyopathy (IDC) and myocarditis at the Regional Cardiac Centre of the Royal
      Hospital for Sick Children, Glasgow, during 1980-1997. Among the 39 patients with
      IDC, 25 (64%) were infants aged < 1 year, eight (20.5%) had wheezing as the
      presenting symptom, and only six (15%) had a significant cardiac murmur. Thirty
      eight of thirty-nine patients diagnosed in life were followed-up for 1 day to 15
      years (median 3 years). Twelve of the thirty-nine (31%) died, six deaths were
      within a week of presentation and the rest within a year. The survival at 1 year
      and at 12 years was 0.69 (95% CI 0.54 to 0.84). Fourteen patients had
      histologically proven myocarditis, and all 9/14 (64%) detected at post-mortem and
      one of the five diagnosed in life died. Patients with myocarditis exhibited an
      actuarial survival of 0.29 (95% CI 0.04 to 0.53) at 1 year and at 9 years,
      significantly lower than IDC patients (log rank 9.8, P < 0.01). There was no
      difference in the outcome for patients with positive or negative Coxsackie titres
      or who presented in the 1980s and in the 1990s. No risk factor that independently
      influenced the outcome or survival could be identified in either group. Thus our
      study from a relatively well-defined population of the west of Scotland showed
      that a significant proportion of children with IDC and myocarditis died in the
      first week of illness and that patients with myocarditis had shorter survival.

PMID- 11334658
TI  - Exercise-induced myocardial ischemia in patients with coronary artery ectasia
      without obstructive coronary artery disease.
AB  - BACKGROUND: Aetiology, clinical significance and treatment options for coronary
      artery ectasia/aneurysm is not clear. OBJECTIVE: We sought to determine whether
      exercise can induce coronary ischemia in patients with coronary artery
      ectasia/aneurysm without significant coronary stenosis. METHODS: Coronary artery
      ectasia was defined as 1.5-2-fold, aneurysm as >2-fold luminal dilatation of the
      adjacent normal segment. The study patients could have irregularities with
      ectatic coronaries but they did not have stenotic lesions >50% with visual
      assessment of two blinded observers. Patients having coronary artery ectasia or
      aneurysm with prior myocardial infarction, dilated cardiomyopathy, valvular heart
      disease, bundle branch block, significant ST-T changes were excluded. The control
      group was formed from a well matched population of 32 patients with normal
      coronary arteries who have not performed a treadmill test before coronary
      angiography. The study group underwent a symptom limited treadmill test if they
      did not have one before coronary angiogram, all control patients underwent
      treadmill test. RESULTS: Thirty-three patients with coronary artery
      ectasia/aneurysm (ranging from one to three vessels) but without significant
      stenosis were derived from 4470 cardiac catheterization procedures between
      January 1998 and July 2000. In the study group, 17 of the patients had positive
      treadmill tests with respect to five patients in the control group (P = 0.004).
      In subgroup analysis, diffuse ectasia/aneurysm (involving 2-3 vessels) was found
      to be strongly related with ischemia (P = 0.005) with respect to local disease.
      CONCLUSION: Coronary artery ectasia/aneurysm may lead to exercise induced
      ischemia, especially in the diffuse form.

PMID- 11334659
TI  - The response of the myocardial metabolism to atrial pacing in patients with
      coronary slow flow.
AB  - The pathophysiology of angina pectoris is not precisely known yet in patients who
      have no coronary lesion but slow coronary flow by angiography. In this study we
      aim to display metabolic ischemia via atrial pacing to determine the difference
      of lactate production and arterio-venous O2 content difference (AVO2). Thirty
      four patients with slow coronary flow detected by coronary angiography via the
      TIMI 'frame count' method were included in this study. The resting and stress
      images from the patients undergoing myocardial perfusion tomography were
      recorded, pre and postpacing lactate extraction and AVO2 content difference
      values were calculated. Patients were classified according to their metabolic
      responses to atrial pacing stress. Group I consisted of 28 patients (18 male, 10
      female, mean age 54.42 +/- 9.61) who did not demonstrate metabolic ischemia and
      group II consisted of six patients (four male, two female, mean age 60 +/- 5.76)
      who had metabolic ischemia after the procedure. There was no statistically
      significant difference between prepacing AVO2 content difference in group I
      (57.38+/-2.05%) and group II (58.23 +/- 2.11%) (P = NS). However postpacing AVO2
      content difference of group I and group II was statistically significant
      (respectively, 57.96+/-2.65 vs. 68.35 +/- 2.15%, P < 0.001). In other words,
      postpacing AVO2 content difference was unchanged from the basal AVO2 content
      difference level in group I (respectively, 57.38 +/- 2.05 vs. 57.96 +/- 2.65%; P
      = NS) in contrast to the postpacing AVO2 content difference which increased
      significantly in group II (58.23 +/- 2.11 vs. 68.35 +/- 2.15%; P < 0.028).
      Although basal lactate extraction rates were similar in groups I and II
      (respectively, 0.24 +/- 0.1 vs. 0.23 +/- 0.18; P = NS), postpacing lactate
      extraction rates were decreased significantly in the two groups, prominently in
      group II (0.154 +/- 0.15 vs. -0.471 +/- 0.27; P < 0.0001) which indicated that
      lactate extraction converted to lactate production. Metabolic ischemia was
      detected in only 17.6% of patients included in this study and 83.4% of these six
      patients with proven metabolic ischemia had perfusion defects in scintigraphy.
      Our data confirmed that angina pectoris was not originated from myocardial
      ischemia in most of the patients with slow coronary flow. We conclude that
      perfusion scintigraphy is a reliable and accurate method for detection of true
      ischemia in this group of patients.

PMID- 11334660
TI  - Assessment of chemoreflex sensitivity in free breathing young subjects by
      correction for respiratory influence.
AB  - BACKGROUND: The assessment of autonomic function is an important tool for risk
      stratification in critically ill patients. Peripheral cardiac chemoreflex
      sensitivity has been considered a marker for increased risk of sudden cardiac
      death. In normals, the evaluation of peripheral cardiac chemoreflex sensitivity
      is performed under controlled breathing conditions during inhalation of hypoxic
      gas. Since this is poorly tolerated by patients, they are commonly studied under
      hyperoxic conditions, which are not physiological. METHODS: We studied 20 healthy
      volunteers who underwent free and controlled breathing of a hypoxic gas mixture
      (10% O2 in N2) over 5 min. Values of peripheral cardiac chemoreflex sensitivity,
      corrected for respiratory influence, were compared with the results obtained
      experimentally under controlled breathing conditions in the same subjects.
      RESULTS: We found a substantial difference between values obtained during free
      and controlled breathing (3.64 +/- 0.81 vs. 1.53 +/- 0.32 ms/mmHg, respectively;
      P < 0.05). After application of a respiratory correction, described and validated
      in this article, no significant difference was seen for these values (0.89 +/
      0.91 vs. 1.53 +/- 0.32 ms/mmHg, P = 0.46). CONCLUSIONS: This approach allows the
      evaluation of peripheral cardiac chemoreflex sensitivity in free breathing
      subjects. This correction could improve the assessment of cardiac chemoreflex
      sensitivity in patients with cardiorespiratory disorders, who find it difficult
      to control their breathing according to an experimental protocol.

PMID- 11334661
TI  - ECG criteria in diagnosis of acute myocardial infarction in the presence of left
      bundle branch block.
AB  - BACKGROUND: The diagnosis of acute myocardial infarction in the presence of left
      bundle branch block is difficult. Recently a diagnostic ECG scoring system was
      suggested, showing good diagnostic abilities. This scoring system has never been
      tested in a prospective manner; we have done so and investigated if it might bear
      prognostic information. METHODS: A prospective multi-centre study. Consecutive
      patients with left bundle branch block and suspicion of acute myocardial
      infarction, admitted to 14 Swedish coronary care units. Recruitment from March
      1996 to December 1997. ECG registered on admission and after 12-24 h. RESULTS:
      One hundred and fifty-eight patients were included, mean age 74.9 years. Seventy
      six patients (48%) had an acute myocardial infarction. The proposed cut-off total
      score of > or = 3 of the ECG scoring system for the diagnosis of acute myocardial
      infarction had a sensitivity of 17.1% (95% CI 8.6-25.6%) and specificity of 94.0%
      (95% CI 88.9-99.1%). Clinical judgement of acute myocardial infarction resulted
      in a sensitivity of 15.8% (95% CI 7.6-24%) and specificity of 96.0% (CI 92.3
      100%). No difference was seen in 3-month or 1-year survival between those with
      total ECG score > or = 3 versus total score < 3. CONCLUSION: The diagnostic
      abilities of the proposed ECG criteria are low and not better than the clinical
      judgement. The criteria are therefore not suitable for screening patients with
      suspicion of acute myocardial infarction in the presence of left bundle branch
      block, nor do they seem to identify high risk patients.

PMID- 11334662
TI  - Infective endocarditis in children--incidence, pattern, diagnosis and management
      in a developing country.
AB  - BACKGROUND: In developing countries, patients with infective endocarditis are
      referred late, there is low yield of blood cultures and incidence of rheumatic
      heart disease is still high. OBJECTIVE: Evaluate clinical pattern, assess
      diagnostic criteria in our settings and determine outcome. SETTING: A tertiary
      referral center for paediatric and adult cardiology. PATIENTS AND METHODS: All
      children with infective endocarditis admitted to a single center from April 1997
      to March 2000 were analysed. The diagnosis was based on Duke's criteria, which
      proposed two major and six minor criteria. Minor criteria were expanded to
      include raised acute phase reactants and presence of newly diagnosed or
      increasing splenomegally. The patients were stratified as definite, possible and
      rejected cases. RESULTS: Of 1402 hospital admissions, 45 patients fulfilled the
      diagnostic criteria for infective endocarditis giving an incidence of 32 per 1000
      hospital admissions. The mean age was 7.9 +/- 4 years (4 months to 16 years) with
      only two patients under 1 year of age. Rheumatic heart disease was the underlying
      lesion in 24 patients (53%) while congenital heart lesions occurred in 20
      patients (45%). Previous antibiotic treatment was given in 26 patients (58%)
      definitely. Blood cultures were positive in 21 patients (47%); Streptococcus
      Viridans being the most common organism, while vegetations on echocardiography
      were present in 32 patients (71%). Surgery was undertaken in four patients and
      five patients left against medical advise. Of 10 patients with aortic valve
      involvement, there were three deaths (30%) and overall mortality was 13% (six
      patients). CONCLUSIONS: The incidence of infective endocarditis is 32 per 1000
      (3.2%) hospital admissions in a tertiary paediatric cardiology referral center.
      Rheumatic heart disease is still the most common underlying heart lesion. Blood
      cultures are positive in less than 50% of cases and echocardiography in expert
      hands is a more sensitive tool in our set up. Mortality is still high and aortic
      valve involvement in particular, carried poor prognosis.

PMID- 11334663
TI  - Enzymatic synthesis of isoamyl acetate using immobilized lipase from Rhizomucor
      miehei.
AB  - The effects of important reaction parameters for enhancing isoamyl acetate
      formation through lipase-catalyzed esterification of isoamyl alcohol were
      investigated in this study. Increase in substrate (acid) concentration led to
      decrease in conversions. A critical enzyme concentration of 3 g l(-1) was
      detected for a substrate concentration of 0.06 M (each of alcohol and acid).
      Solvents with partition coefficient higher than 1000 (log P>3.0) supported enzyme
      activity to give high conversions. Acetic acid at higher concentrations could not
      be esterified easily probably owing to its role in lowering the microaqueous pH
      of the enzyme. Extraneous water/buffer addition decreased the isoamyl acetate
      yields slightly ( approximately 10%) at 0.005-0.01% v/v of the reaction mixture
      and drastically (>40%) at above 0.01% v/v. Buffer saturation of the organic
      solvent employed improved esterification (upto two-fold), particularly at
      moderately higher substrate concentrations (>0.18 M). Employing acetic anhydride
      instead of acetic acid resulted in a two-fold increase in the yields (at 0.25 M
      substrate). Use of excess nucleophile (alcohol) concentration by increasing the
      alcohol/acid molar ratio resulted in higher conversions in shorter duration (upto
      eight-fold even at 1.5 M acetic acid). Yields above 80% were achieved with
      substrate concentrations as high as 1.5 M and more than 150 g l(-1) isoamyl
      acetate concentrations were obtained employing a relatively low enzyme
      concentration of 10 g l(-1). The operational stability of lipase was also
      observed to be reasonably high enabling ten reuses of the biocatalyst.

PMID- 11334664
TI  - Improvement of the optimum temperature of lipase activity for Rhizopus niveus by
      random mutagenesis and its structural interpretation.
AB  - Random mutagenesis was used to improve the optimum temperature for Rhizopus
      niveus lipase (RNL) activity. The lipase gene was mutated using the error-prone
      PCR technique. One desirable mutant was isolated, and three amino acids were
      substituted in this mutant (P18H, A36T and E218V). The wild-type and this
      randomly mutated lipase were both purified and characterized. The specific
      activity of the mutant lipase was 80% that of the wild-type. The optimum
      temperature of the mutant lipase was higher by 15 degrees C than that of the wild
      type. To confirm which substitution contributed to enhancing the optimum
      temperature for enzymic activity, two chimeric lipases from the wild-type and
      randomly mutated gene were constructed: chimeric lipase 1 (CL-1; P18H and A36T)
      and chimeric lipase 2 (CL-2; E218V). Each of the chimeric enzymes was purified,
      and the optimum temperature for lipase activity was measured. CL-1 had a similar
      optimum temperature to that of the wild-type, and CL-2 had a higher temperature
      like the randomly mutated lipase. The mutational effect is interpreted in terms
      of a three-dimensional structure for the wild-type lipase.

PMID- 11334665
TI  - Mathematical model for evaluation of mass transfer limitations in phenol
      biodegradation by immobilized Pseudomonas putida.
AB  - A mathematical model is proposed to analyze the mass transfer limitations in
      phenol biodegradation using Pseudomonas putida immobilized in calcium alginate.
      The model takes into account internal and external mass transfer limitations,
      substrate inhibition kinetics and the dependence of the effective diffusivity of
      phenol in alginate gel on cell concentration. The model is validated with the
      experimental data from batch fermentation. The effect of various operating
      conditions such as initial phenol concentration, initial cell loading, alginate
      gel loading on the biodegradation of phenol is experimentally demonstrated.
      Phenol degradation time is found to decrease initially and reach stationary value
      with increase in cell loading as well as gel loading. The model predicts these
      trends reasonably well and shows the presence of external mass transfer
      limitations. A new concept of effectiveness factor is introduced to analyze the
      overall performance of batch fermentation.

PMID- 11334666
TI  - Engineering the pH-optimum of a triglyceride lipase: from predictions based on
      electrostatic computations to experimental results.
AB  - The optimisation of enzymes for particular purposes or conditions remains an
      important target in virtually all protein engineering endeavours. Here, we
      present a successful strategy for altering the pH-optimum of the triglyceride
      lipase cutinase from Fusarium solani pisi. The computed electrostatic pH
      dependent potentials in the active site environment are correlated with the
      experimentally observed enzymatic activities. At pH-optimum a distinct negative
      potential is present in all the lipases and esterases that we studied so far.
      This has prompted us to propose the "The Electrostatic Catapult Model" as a model
      for product release after cleavage of the ester bond. The origin of the negative
      potential is associated with the titration status of specific residues in the
      vicinity of the active site cleft. In the case of cutinase, the role of Glu44 was
      systematically investigated by mutations into Ala and Lys. Also, the neighbouring
      Thr45 was mutated into Proline, with the aim of shifting the spatial location of
      Glu44. All the charge mutants displayed altered titration behaviour of active
      site electrostatic potentials. Typically, the substitution of the residue Glu44
      pushes the onset of the active site negative potential towards more alkaline
      conditions. We, therefore, predicted more alkaline pH optima, and this was indeed
      the experimentally observed. Finally, it was found that the pH-dependent computed
      Coulombic energy displayed a strong correlation with the observed melting
      temperatures of native cutinase.

PMID- 11334667
TI  - Stability of an extreme halophilic alkaline phosphatase from Halobacterium
      salinarium in non-conventional medium.
AB  - Alkaline p-nitrophenylphosphate phosphatase from the halophilic archaeon
      Halobacterium salinarum (earlier halobium) was solubilised in organic medium
      using reversed micelles of hexadecyltrimethylammonium bromide in cyclohexane,
      with 1-butanol as co-surfactant. The stability of alkaline p-nitrophenylphosphate
      phosphatase in this system was studied at different conditions, w(0)
      ([H(2)O]/[surfactant]), salt concentration, with and without Mn(+2). At all the
      conditions assayed, alkaline p-nitrophenylphosphate phosphatase was more stable
      in reversed micelles than in bulk aqueous solution (at 25 degrees C). The
      stabilisation effect of the reversed micelles was dramatic when the enzyme was
      dialysed against Mn(+2)-free buffer since the enzyme lost all the activity within
      90 min in aqueous medium, but it retained approximately 72% of the initial
      enzymatic activity for 90 min in reversed micelles.

PMID- 11334668
TI  - Purification of lactonic sophorolipids by crystallization.
AB  - Various experimental methods for purifying lactonic sophorolipids (SLs) via
      crystallization were studied. The commonly used solvent, ethanol, was found to
      have much higher solubility of the lactonic SLs than the acid SLs. Consequently,
      for purification of lactonic SLs, ethanol not only lacked the selectivity in
      removing acidic SLs but also resulted in significant loss of desired products.
      Aqueous buffers were subsequently studied as the solvent, based on the rationale
      that acidic SLs, having the free carboxylic acid group(s), are more hydrophilic
      than the lactonic SLs, especially at higher pH. Both phthalate and phosphate
      buffers were found more suitable for purifying lactonic SLs than ethanol. A
      practical and effective method for purifying lactonic SLs to about 99% purity
      using phosphate buffers was developed. The FTIR spectra also showed significantly
      less SL components with free acid groups in the purified SLs than in the crude
      SLs, confirming the removal of acidic SLs in the purification.

PMID- 11334669
TI  - Bioadsorption of lead(II) from aqueous solution by fungal biomass of Aspergillus
      niger.
AB  - The removal of lead by waste fungal biomass of Aspergillus niger, originated from
      citric acid fermentation industry, was investigated. The experimental results
      indicated that the bioadsorption achieved equilibrium within 4 h. The kinetic
      analysis of lead adsorption onto the fungal biomass revealed that the
      bioadsorption process followed the first-order reaction kinetics. The adsorption
      isotherm can be simulated by Freundlich model, which gave a correlation
      coefficient equal to 0.93. The lead-loaded biomass can be effectively regenerated
      by 0.1 M nitric acid. This research demonstrated that the waste biomass of A.
      niger is a potential bioadsorbent for the removal of lead from aqueous solution.

PMID- 11334670
TI  - Human xenospecific T suppressor cells inhibit T helper cell proliferation to
      porcine aortic endothelial cells, and NF-kappaB activity in porcine APC.
AB  - Human T suppressor cells (Ts), capable of preventing autologous T helper cells
      (Th) from reacting against xenogeneic pig endothelial cells and pig APC can be
      generated in vitro. Ts derive from a population of CD3(+)CD8(+)CD28(-) T
      lymphocytes and specifically recognize the MHC class I antigens of the APC used
      for in vitro immunization. To study the mechanism that underlies suppression, we
      investigated whether Ts inhibit the expression of costimulatory molecules in
      xenogeneic professional and semiprofessional APC. We found that Ts down-regulate
      Th-induced expression of CD86 in pig APC, and that this effect occurs at the
      level of transcription, as indicated by nuclear run-on and Northern blot assays.
      EMSA results revealed that inhibition of CD86 expression is mediated by
      inactivation of transcription factor NF-kappaB. Furthermore, transfection of pig
      APC with a vector expressing NF-kappaB p65 partially rescued Th-induced
      expression of the CD86 molecule. These results strongly support the concept that
      xenospecific Ts inhibit the APC function of xenogeneic cells by preventing
      activation of NF-kappaB.

PMID- 11334671
TI  - Phenotypic and functional analysis of T-cell recovery after anti-CD3 immunotoxin
      treatment for tolerance induction in rhesus macaques.
AB  - T-cell reduction utilizing specific antibody has been widely used in human
      transplantation, and is a cornerstone of several tolerance induction strategies
      in nonhuman primates. We have established a population of long-term tolerant
      rhesus macaques induced with an anti-CD3epsilon immunotoxin (IT). This treatment
      effects transient, specific and profound ablation of T cells in blood and
      lymphoid tissues. In most instances the IT was used in combination with the NF
      kappaB inhibitor, 15-Deoxyspergualin. This 2-week long protocol produces a
      "window of opportunity" for tolerization in which the animal exhibits an enduring
      quiescent state of unresponsiveness to the allograft, all accomplished without
      maintenance immunosuppressive drugs. During this induction period, the treated
      immune system bears some resemblance to that of the neonate, in that T cell
      numbers are abnormally low and antigen presentation by dendritic cells is
      precluded by an arrest in their NF-kappaB dependant maturation. In addition, IL-4
      production is prominent during and after the tolerance induction interval. For
      this study we focused on measuring the monkey's ability to repopulate T cells
      with particular emphasis on the memory T-cell phenotype. Three "memory"
      phenotypes were utilized; CD3(+)CD45RO(+), CD3(+)CRTH2(+), and
      CD3(+)CD4(+)CD8(+). All three phenotypes exhibited different patterns of
      recovery, all of which included transient bursts in their numbers during
      repopulation. We also estimated thymic activity after T-cell ablation with the
      use of a newly-described RTE or recent thymic emigre phenotype (a naive
      CD8(+)CD103(+) T cell). This marker revealed production of RTE cells including
      supranormal levels at approximately 6 months post-transplant, implicating thymic
      function in the repopulation of T-cells. Finally, we measured antibody responses
      to a panel of antigens (vaccines, environmental antigen, and foreign proteins)
      that indicated there was no apparent loss of immunologic function during or after
      the tolerance induction period. Results of studies of T-cell receptor repertoire
      expression suggest preservation of the pretreatment repertoire, which is
      consistent with rapid recovery of immune competence to the test antigens. Taken
      together, these results suggest that while aggressive, this tolerance induction
      protocol does not appear to incur a prolonged immunologically-compromised state,
      if at all.

PMID- 11334672
TI  - T-cell receptor repertoire in hereditary hemochromatosis: a study of 32
      hemochromatosis patients and 274 healthy subjects.
AB  - Low CD8(+) T lymphocyte numbers have contributed to deciphering the
      genotype/phenotype discrepancies found in hereditary hemochromatosis (HH)
      patients genotyped for the Hfe mutations, C282Y and H63D. In this study, we
      extend the analysis of T lymphocytes in HH to the T cell receptor (TcR)
      repertoire. Thirty-two HH patients (C282Y homozygous) and 274 Hfe genotyped
      healthy subjects were studied. The following TcR chains were analyzed: Valpha2.3,
      Vbeta5.1, Vbeta5.2, Vbeta5.3, Vbeta6.7, Vbeta8, and Vbeta12 among the CD4(+) and
      CD8(+) populations. Lymphopenias and absence of expansions of the Vbeta5.2 and
      Vbeta12 chains in the CD8(+) pool were seen in controls heterozygous for the
      C282Y mutation. Expansions in the control group were seen within the CD8(+) pool
      and were rare/absent within the CD4(+) pool. TcR expansions were found more
      frequent in patients with iron overload related pathology than in patients
      without pathology. 9/16 of the patients with pathology have at least one
      expansion among the CD8(+) pool a number significantly higher compared with
      patients without pathology (1/16). These findings suggest that Hfe has an effect
      in the shaping of T-cell populations either directly, as indicated by the
      lymphopenia seen in the two chains in C282Y heterozygous without iron overload,
      or indirectly by contributing to iron overload pathology.

PMID- 11334673
TI  - Immune reconstitution after hematopoietic stem cell transplantation: gaining
      experience without losing naivety.
AB  - In addition to lymphocyte phenotyping and functional assays, new tools are now
      available to monitor specific aspects of the immune response in the follow-up of
      hematopoietic stem cell transplantation: reconstitution of T-cell diversity
      (spectratyping or immunoscope), ex vivo thymic function by measuring "T-cell
      receptor rearrangement excision DNA circles" and antigen-specific T-cell
      responses (HLA tetramers). Combining these methods should contribute to improve
      our current knowledge of how the immune system is reconstituted in different
      settings of hematopoietic stem cell transplantation and how we could improve this
      recovery process.

PMID- 11334675
TI  - Association analysis of HLA-class II and class III gene polymorphisms in the
      susceptibility to mediterranean visceral leishmaniasis.
AB  - HLA-DRB1, -DQB1, TNFalpha, TNFbeta, HSP70-2 and HSP70-hom genetic polymorphisms
      were analyzed in 156 unrelated patients who developed mediterranean visceral
      leishmaniasis (MVL) due to Leishmania infantum, and 154 unrelated healthy
      controls, who have got asymptomatic infection with this parasite and were
      selected on the basis of a positive leishmanin skin test (LST). A significantly
      reduced frequency of HLA-DR2 was observed among MVL patients (16.1%), compared
      with controls (26.3%) (relative risk = 0.54; p = 0.04). HLA-DR2/DR13 as well as
      HLA-DQB1*0201/- genotype frequencies were significantly lower in patients vs
      controls (relapse rate = 0.17 and 0.46, respectively; p < 0.05). However, using
      Bonferroni correction, none of these associations remained significant. No
      association was found, between either the -308 base pair TNFalpha gene
      polymorphism or the NcoI polymorphism in the first intron of the TNFbeta gene and
      susceptibility to MVL. Analysis of PstI and NcoI polymorphisms in the coding
      region of HSP70-2 and HSP70-hom genes, respectively, revealed a significantly
      higher frequency of homozygotes for the HSP70-2/PstI negative allele, among
      patients (21.8%) vs controls (12.6%) (relapse rate = 1.94; p = 0.04). Again, this
      result was not significant after using Bonferroni correction. These results do
      not support association between susceptibility to MVL and the MHC class II and
      class III loci analyzed in this study.

PMID- 11334674
TI  - Absence of in vivo DNA-protein interactions in the DQA2 and DQB2 promoter
      regions.
AB  - The DQ subregion of the human major histocompatibility complex (HLA) contains two
      pairs of loci: the DQA1/B1 genes (hereafter called DQ1), coding for the DQ
      molecules, and the DQA2/B2 pseudogenes (hereafter called DQ2). These pseudogenes
      are highly homologous to the functional DQ1 genes and they have no apparent
      abnormal features in their sequences that could prevent their activity. Only
      recently a low expression of the DQA2 gene has been observed whereas the DQB2
      transcript was never found. The comparison between the DQ1 and DQ2 regulatory
      sequences revealed several differences in their W, X, and Y cis-acting elements.
      To examine the DNA/protein interactions in the DQ promoter regions, we performed
      in vivo footprinting experiments. Whereas the functional DQ1 loci showed a series
      of DNA-protein contact points in the X and Y boxes, the promoters of the DQ2
      pseudogenes displayed an unoccupied phenotype. These findings suggest that the
      very low level of DQA2 expression and the apparent lack of DQB2 activity are
      caused by the reduced binding affinity of specific transcription factors.

PMID- 11334677
TI  - Protection against severe disease is conferred by DERAA-bearing HLA-DRB1 alleles
      among HLA-DQ3 and HLA-DQ5 positive rheumatoid arthritis patients.
AB  - Experimental studies in transgenic mice have suggested that HLA-DQ predisposes to
      rheumatoid arthritis (RA), but could also modulate disease severity by presenting
      peptides derived from self-DR molecules. In particular, a short amino acid
      sequence, (70)DERAA(74), in the third hypervariable region of HLA-DRB1 confers
      protection for the disease, while particular HLA-DQ [DQB1*0501/DQA1*01 (DQ5) and
      DQB1*03/DQA1*03 (DQ3)] molecules predispose to the disease. We have therefore
      analyzed the allelic distribution of HLA-DRB1, DQA1, and DQB1 and the presence of
      rheumatoid factor and nodules among 199 German RA patients and 196 healthy
      controls. Our results show that HLA-DQB1*03/DQA1*03 (or DRB1*04) predisposes to
      RA more than HLA-DQB1*0501/DQA1*01 (i.e., DRB1*01 and DRB1*10). Homozygosity for
      DQ3 confers the strongest genetic risk for RA (OR = 19.79 compared to OR = 10.05
      for two doses of shared epitope (SE) positive HLA-DRB1 alleles). Furthermore,
      patients carrying both predisposing DQ and (70)DERAA(74)-positive HLA-DRB1
      alleles are more often rheumatoid factor (RF) negative than patients carrying
      predisposing DQ alleles alone. Only one out of 14 patients (7%) with a protective
      combination (DQ3/(70)DERAA(74) and DQ5/(70)DERAA(74)) had rheumatoid nodules
      compared to 67 out of 144 patients (46.5%) with predisposing DQ alleles alone (OR
      = 0.12, 95% CI: 0.02-0.72, p = 0.004). These results demonstrate a protective
      role of (70)DERAA(74)-positive DRB1 alleles against disease severity among RA
      patients.

PMID- 11334676
TI  - Polymorphism in gene for islet autoantigen, IA-2, and type 1 diabetes in Japanese
      subjects.
AB  - Autoantibodies against IA-2 have been detected in up to 86% of newly diagnosed
      patients with type 1 diabetes and appear to identify a subgroup of prediabetic
      subjects who rapidly progress to type 1 diabetes. We examined the association of
      IA-2 gene polymorphism with type 1 diabetes in Japanese subjects. A total of 276
      Japanese subjects were studied for disease association and, in addition, another
      53 patients were studied for association with the autoantibody status to IA-2. A
      microsatellite marker D2S1753E, located in the intron of the IA-2 gene, was used
      as a genetic marker in this study. In Japanese, two alleles (161mu and 165mu)
      were more frequent, and the 163mu allele was less frequent than in Caucasians (p
      = 0.0001). There was no significant difference in frequencies of alleles between
      diabetic patients and control subjects. The frequency of IA-2 gene polymorphism
      was not significantly different between patients stratified by age-at-onset, or
      between patients with and without susceptible HLA, DRB1*0405, DRB1*0802 and
      DRB1*0901. There was no significant difference in allele frequency of the IA-2
      gene polymorphism between patients with and without autoantibody to IA-2. In
      conclusion, IA-2 gene polymorphism is not associated with either susceptibility
      to, or heterogeneity in type 1 diabetes in Japanese subjects.

PMID- 11334678
TI  - Evolution of the CCR5 Delta32 mutation based on haplotype variation in Jewish and
      Northern European population samples.
AB  - The chemokine receptor 5 (CCR5) serves as a fusion cofactor for macrophage-tropic
      strains of HIV-1. In addition, CCR5 has been shown to mediate the entry of
      poxviruses into target cells. Individuals homozygous for the Delta32 deletion
      mutation have no surface expression of CCR5 and are highly protected against HIV
      1 infection. To gain insights into the evolution of the mutation in modern
      populations, the relatively high frequency of the Delta32-ccr5 allele in some
      European and Jewish populations is explored here by examining haplotypes of
      3p21.3 constructed of five polymorphic marker loci surrounding CCR5. By sampling
      Ashkenazi, non-Ashkenazi and non-Jewish populations, we utilize the natural
      experiment that occurred as a consequence of the Jewish Diaspora, and demonstrate
      that a single mutation was responsible for all copies of Delta32. This mutation
      must have moved from Northern European populations to the Ashkenazi Jews where
      evidence suggests that Delta32 carriers of both groups were favored by repeated
      occurrence of epidemic small pox beginning in the 8th century AD.

PMID- 11334679
TI  - Towards the MHC-peptide combinatorics.
AB  - The exponentially increased sequence information on major histocompatibility
      complex (MHC) alleles points to the existence of a high degree of polymorphism
      within them. To understand the functional consequences of MHC alleles, 36
      nonredundant MHC-peptide complexes in the protein data bank (PDB) were examined.
      Induced fit molecular recognition patterns such as those in MHC-peptide complexes
      are governed by numerous rules. The 36 complexes were clustered into 19 subgroups
      based on allele specificity and peptide length. The subgroups were further
      analyzed for identifying common features in MHC-peptide binding pattern. The four
      major observations made during the investigation were: (1) the positional
      preference of peptide residues defined by percentage burial upon complex
      formation is shown for all the 19 subgroups and the burial profiles within
      entries in a given subgroup are found to be similar; (2) in class I specific 8-
      and 9-mer peptides, the fourth residue is consistently solvent exposed, however
      this observation is not consistent in class I specific 10-mer peptides; (3) an
      anchor-shift in positional preference is observed towards the C terminal as the
      peptide length increases in class II specific peptides; and (4) peptide backbone
      atoms are proportionately dominant at the MHC-peptide interface.

PMID- 11334680
TI  - The abdominal compartment syndrome: a complication with many faces.
AB  - BACKGROUND: Lately renewed attention has been given to the abdominal compartment
      syndrome. Despite of this there still remain a lot of controversies with regard
      to the pathophysiological mechanisms underlying this syndrome and the therapeutic
      options. METHODS: Two cases of patients with this syndrome are described and the
      data from animal and human trials concerning the abdominal compartment syndrome
      are presented and discussed. RESULTS: A variety of clinical disorders may lead to
      the abdominal compartment syndrome. It mainly affects the cardiovascular,
      pulmonary and renal organ systems. Although some clinical effects are clearly
      described, the exact mechanisms underlying these changes in humans are
      incompletely understood. It is still unclear why some patients develop abdominal
      compartment syndrome and others do not. The intra-abdominal pressure can easily
      be assessed by measuring the urine bladder pressure, which correlates well with
      the actual intra-abdominal pressure. All authors agree that a decompression of
      the abdomen by means of a laparotomy is the treatment of choice for the abdominal
      compartment syndrome. Which parameters should determine the indication however,
      remains controversial, since the correlation between clinical signs and pressure
      is not straightforward. CONCLUSIONS: The abdominal compartment syndrome is a well
      recognised disease entity related to acutely increased abdominal pressure. Urgent
      laparotomy can be lifesaving in some cases. However no single threshold of
      abdominal pressure can be applied universally. Pending further clinical trials
      the best therapeutic option seems to be to decompress the abdomen surgically if
      the intravesical pressure is 25 mmHg or higher in patients with refractory
      hypotension, acute renal failure or respiratory failure due to abdominal
      distension.

PMID- 11334681
TI  - Intravascular hemolysis by IgA red cell autoantibodies.
AB  - A 66-year-old male patient with severe intravascular hemolysis is presented.
      Laboratory investigation revealed initially a negative direct antiglobulin test
      (DAT), suggesting a Coombs-negative hemolytic anemia. Additional testing with
      monospecific anti-IgA was strongly positive. IgA autoantibodies with anti-e
      specificity and nonspecific IgA autoantibodies were identified. A diagnosis of
      IgA-only-associated warm AIHA was made. Treatment included transfusion of
      multiple e-negative typed red cell concentrates and administration of high-dose
      prednisone. The pathophysiologic mechanism of the rare IgA-induced warm AIHA is
      discussed.

PMID- 11334682
TI  - Malabsorption syndrome in a patient of Mediterranean origin; immunoproliferative
      small intestinal disease.
AB  - We describe a 30-year-old woman of Turkish descent presenting with abdominal pain
      and signs of malabsorption. The cause of her complaints turned out to be
      immunoproliferative small intestinal disease which is a very uncommon disorder in
      our geographical region. We discuss the differential diagnosis of this disease
      and the therapeutical options.

PMID- 11334685
TI  - John Snow and resuscitation.

PMID- 11334686
TI  - Patient outcomes following defibrillation with a low energy biphasic truncated
      exponential waveform in out-of-hospital cardiac arrest.
AB  - PRIMARY OBJECTIVE: To determine the outcome of patients with out-of-hospital
      cardiac arrest and ventricular fibrillation as the presenting rhythm while using
      automated external defibrillators (AEDs) that delivered non-escalating, impedance
      compensated low-energy (150 J) shocks. MATERIALS AND METHODS: AEDs delivering low
      energy biphasic truncated exponential (BTE) shocks were employed in an emergency
      medical services (EMS) system in which first-arriving personnel - police,
      firefighters or paramedics - delivered the initial shocks. Patients were
      classified according to their response to shocks: restoration of sustained
      spontaneous circulation (ROSC) without need for epinephrine and other advanced
      life support (ALS) interventions; and ALS, those requiring epinephrine in all
      instances. The primary end-point was neurologically-intact discharge survival.
      Secondary end-points were ROSC with shocks only and the call-to-shock time
      interval. RESULTS: Of 42 patients with VF arrest treated with BTE shocks, 35 were
      bystander-witnessed. Of these 35, 14 (38%) regained a sustained ROSC on-scene
      with shocks only, needing no epinephrine for ROSC. All 14 survived to discharge
      home. Of the remaining 21 patients needing ALS intervention, only two (9.5%)
      survived to discharge. Overall, 16/35 patients (46%) survived to discharge home,
      an outcome comparable to our experience with patients treated with escalating
      high-energy monophasic waveform shocks. CONCLUSIONS: Low-energy (150 J) non
      escalating biphasic truncated exponential waveform shocks terminate VF in out-of
      hospital cardiac arrest with high efficacy; patient outcome is comparable with
      that observed with escalating high-energy monophasic shocks. Low-energy shocks,
      in addition to high efficacy, may confer the advantage of less shock-induced
      myocardial dysfunction, though this will be difficult to define in the clinical
      circumstance of long-duration VF provoked by a pre-existing diseased myocardial
      substrate.

PMID- 11334687
TI  - Is there a difference between women and men in characteristics and outcome after
      in hospital cardiac arrest?
AB  - AIM: To describe the characteristics and outcome among patients suffering from an
      in-hospital cardiac arrest in women and men. METHODS: All patients who suffered
      an in-hospital cardiac arrest during a 4 year period in Sahlgrenska Hospital
      Goteborg, Sweden, where the cardiopulmonary resuscitation (CPR) team was called,
      were recorded and described prospectively in terms of characteristics and
      outcome. RESULTS: There were 557 patients suffering in-hospital cardiac arrest in
      whom the CPR-team was alerted. Among them, 217 (39%) were women. Women differed
      from men having a lower prevalence of earlier myocardial infarction, angina
      pectoris, renal disease and a higher prevalence of rheumatic disease. In terms of
      aetiology of the cardiac arrest, 47% men and 48% women were judged to have had a
      confirmed or possible AMI. More men than women were found in ventricular
      fibrillation/ventricular tachycardia (VF/VT) (57 vs. 41%; P<0.001), whereas more
      women were found in pulseless electrical activity (30 vs. 15%; P<0.0001).
      Cerebral performance categories (CPC)-score at discharge did not differ between
      men and women. Among women, 36.4% survived to discharge as compared with 38.0%
      among men (NS). Survival from VF/VT was 64.3% in women and 52.7% in men (NS).
      When correcting for dissimilarities at baseline, the adjusted odd ratio for being
      discharged alive from hospital among women as compared with men was 1.66 (95%
      confidence limit 1.06-2.62; P=0.028). CONCLUSION: Thirty nine percent of patients
      suffering in-hospital cardiac arrest for whom the CPR-team was alerted, were
      women. Women were less frequently found in VF/VT than men. After correcting for
      dissimilarities at baseline, female gender was associated with a small
      improvement in survival.

PMID- 11334688
TI  - Chain of survival: differences in early access and early CPR between policemen
      and high-school students.
AB  - Immediate activation of the emergency medical service (EMS) and cardiopulmonary
      resuscitation (CPR) increases the incidence of return of spontaneous circulation
      and the number discharged from hospital. The American Heart Association (AHA) and
      the European Resuscitation Council describe CPR as an ordinate sequence of eight
      steps. The objectives of this study were to assess the general knowledge of EMS
      and CPR and to analyse the retention of the CPR steps 2 months after a Basic Life
      Support (BLS)-course conducted according to AHA standards. We studied two
      populations from the same geographical area, law enforcement agents (LEA), since
      they are often the first to intervene, and high school students (HSS) since they
      are more likely to participate in such courses. HSS were more responsive and
      receptive than LEA. In order to increase the retention of the sequence of CPR
      steps, the number of steps should be reduced and refresher courses should be
      included in training programmes. Early access and early CPR are still not
      completely effective in the geographical area studied.

PMID- 11334689
TI  - Developing leaders for advanced life support: evaluation of a training programme.
AB  - AIM: To evaluate the effectiveness of a leadership development seminar introduced
      into the Resuscitation Council (UK) Advanced Life Support (ALS) Provider course.
      METHODS: Observational assessments of leadership performance during cardiac
      arrest scenarios before and after a leadership seminar. RESULTS: The leadership
      training programme significantly improved candidates leadership performance in
      the training situation. CONCLUSION: A formal leadership development programme
      should be introduced into advanced life support courses.

PMID- 11334690
TI  - Team performance in the emergency room: assessment of inter-disciplinary
      attitudes.
AB  - In-hospital emergency medicine in central Europe relies on inter-disciplinary co
      operation. To improve team performance in the emergency room (ER), a
      questionnaire for assessment of attitudes and judgements in resuscitation
      procedures was developed. A total of 43 items were evaluated according to a five
      point Likert scale. With a response rate of 81%, 143 questionnaires were
      evaluated. Assessment of data was performed with regard to professional
      speciality and level in the medical hierarchy. Factorial analysis identified four
      main factors: Assessment of 'quality of performance' (F1), 'importance of
      structure' (F2), 'quality of team culture' (F3), and 'importance of hierarchy'
      (F4). Influences from the categories 'speciality' and 'hierarchy' and from the
      covariate 'gender' on these main factors were evaluated by two-factorial analysis
      of variance. For all four factors, 'speciality' produced significant differences.
      Surgeons accorded high values to F1 and low values to F2, whereas
      anaesthesiologists accorded low values to F1 and high values to F2. F3 showed a
      low ranking from within the ER nursing staff and the residents in internal
      medicine, whereas F4 received high scores by medical residents and staff members.
      For F1 and F3, there was a tendency towards hierarchy dependency, whereas no
      factor was influenced by gender. In conclusion, team performance in the ER is
      mainly influenced by different perceptions and attitudes of the different
      disciplines involved in the resuscitation process.

PMID- 11334691
TI  - Usefulness of two-dimensional echocardiography and myocardial perfusion imaging
      for immediate evaluation of chest pain in the emergency department.
AB  - BACKGROUND: Accurate identification of patients in the emergency department at
      high risk of acute coronary syndrome with possible myocardial ischaemia and a
      nonischaemic electrocardiogram is problematic. Both two-dimensional
      echocardiography and myocardial perfusion imaging with technetium-99m-sestamibi
      can identify patients at low and high risk, however comparative studies are
      lacking. METHODS AND RESULTS: We studied 655 consecutively patients considered at
      low or moderate risk for myocardial ischaemia in our Emergency Department (ED).
      On the basis of the presenting history, physical examination, and
      electrocardiogram they underwent both echocardiography and myocardial perfusion
      imaging within 4 h of ED presentation. End points included myocardial infarction,
      percutaneous transluminal coronary angioplasty (PTCA) and positive stress
      perfusion imaging. Both imaging procedures were performed in the ED on 470
      patients. Overall agreement between the two techniques was high (concordance 90%)
      in the patients who had myocardial infarction or underwent coronary angiography.
      CONCLUSIONS: Agreement between the two imaging techniques is high when used in
      patients with possible myocardial ischaemia. Both techniques identified patients
      at high risk who required admission and those who could be safely discharged
      directly from the ED.

PMID- 11334692
TI  - The effect of single-handed cricoid pressure on cervical spine movement after
      applying manual in-line stabilisation -- a cadaver study.
AB  - Six adult cadavers had 40 N cricoid pressure applied using a cricoid 'yoke'
      whilst maintaining manual in-line stabilisation of the cervical spine. No other
      spinal supports were used. Lateral radiographs were taken before and after
      applying pressure to the cricoid cartilage and the degree of cervical spine
      movement accurately determined. The median vertical displacements measured from
      the body of C5 and two other reference points (A and B) on the cervical spine
      were 0.5 mm (range 0-1.5 mm) and 0.5 mm (range 0-3 mm), respectively. There was
      no disruption to the lines formed by the anterior or posterior borders of the
      cervical bodies. We have been unable to demonstrate that single-handed cricoid
      pressure causes clinically significant displacement of the cervical spine in a
      cadaver model. This conflicts with previous studies.

PMID- 11334693
TI  - Differences in the pharmacodynamics of epinephrine and vasopressin during and
      after experimental cardiopulmonary resuscitation.
AB  - Vasopressin has been investigated as a possible alternative to epinephrine during
      cardiopulmonary resuscitation (CPR). We tested the hypothesis that vasopressin,
      in comparison with epinephrine, would improve cerebral blood flow and metabolism
      during CPR as well as after restoration of spontaneous circulation (ROSC). A
      total of 22 anaesthetised piglets were subjected to 5 min of ventricular
      fibrillation followed by 8 min of closed-chest CPR. The piglets were randomly
      allocated to receive repeated boluses of either 45 microg/kg epinephrine or 0.4
      U/kg vasopressin IV. Haemodynamic parameters, cerebral cortical blood flow and
      cerebral tissue pH and PCO(2) were continuously monitored during CPR and up to 4
      h after ROSC. Cerebral oxygen extraction ratio was calculated. Cerebral cortical
      blood flow increased transiently after each bolus of epinephrine, while only the
      first bolus of vasopressin resulted in a sustained increase. The peak in cerebral
      cortical blood flow was reached approximately 30 s later with vasopressin. During
      the initial 5 min following ROSC, cerebral cortical blood flow was greater in the
      vasopressin group. In conclusion, there is a difference between epinephrine and
      vasopressin in the time from injection to maximal clinical response and the
      duration of their effect, but their overall effects on blood pressures and
      cerebral perfusion do not differ significantly during CPR. In contrast,
      vasopressin results in a greater cerebral cortical blood flow during a transient
      period after ROSC.

PMID- 11334694
TI  - The effect of mild hypothermia and induced hypertension on long term survival
      rate and neurological outcome after asphyxial cardiac arrest in rats.
AB  - STUDY OBJECTIVE: we studied the long-term effect of a combined treatment with
      resuscitative mild hypothermia and induced hypertension on survival rate and
      neurological outcome after asphyxial cardiac arrest (CA) in rats. METHODS: 36
      male Wistar rats, were randomised into three groups: Group I (n=10):
      anaesthetised with halothane and N(2)O/O(2) (70/30%) had vessel cannulation but
      no asphyxial CA; mechanical ventilation was continued to 1 h. Group II (n=13):
      under the same anaesthetic conditions and vessel cannulation, was subjected to
      asphyxial CA of 8 min, reversed by brief external heart massage and followed by
      mechanical ventilation to 1 h post restoration of spontaneous circulation (ROSC).
      Group III (n=13): received the same insult and resuscitation as described in
      group II, but in contrast to the previous group, a combination treatment of
      hypothermia (34 degrees C) and induced hypertension was started immediately after
      ROSC and maintained for 60 min ROSC. Survival rate and neurological deficit (ND)
      scores were determined before arrest, at 2 and 24 h, and each 24-h up to 4 weeks
      after ROSC. RESULTS: Baseline variables were the same in the three groups.
      Comparison of the asphyxial CA groups (groups II and III), showed an increased,
      although not statistically significant, survival rate at 72 h after ROSC in group
      III, and it became highly significant at 4 weeks after ROSC. The ND scores were
      the same in both asphyxial CA groups (groups II and III). CONCLUSIONS:
      Resuscitative mild hypothermia and induced hypertension after asphyxial CA in
      rats is associated with a better survival rate. This beneficial effect persisted
      for 4 weeks after ROSC.

PMID- 11334695
TI  - Thiopental and phenytoin by aortic arch flush for cerebral preservation during
      exsanguination cardiac arrest of 20 minutes in dogs. An exploratory study.
AB  - We are systematically exploring in our exsanguination cardiac arrest (CA) outcome
      model in dogs suspended animation (SA), i.e. immediate preservation of brain and
      heart for resuscitative surgery during CA, with delayed resuscitation. We have
      shown in dogs that inducing moderate cerebral hypothermia with an aortic arch
      flush of 500 ml normal saline solution of 4 degrees C, at start of CA 20 min no
      flow, leads to normal functional outcome. We hypothesized that, using the same
      model, adding thiopental (or even better thiopental plus phenytoin) to the flush
      at ambient temperature (24 degrees C), which would be more readily available in
      the field, will also achieve normal functional outcome. Thirty dogs (20-28 kg)
      were exsanguinated over 5 min to CA of 20 min no-flow, and resuscitated by closed
      chest cardiopulmonary bypass. They received assisted circulation to 2 h, 34
      degrees C post-CA to 12 h, controlled ventilation to 20 h, and intensive care to
      72 h. At CA 2 min, the dogs received an aortic arch flush of 500 ml saline at 24
      degrees C by a balloon-tipped catheter, inserted through the femoral artery
      (control group 1, n=14). In group 2 (n=9), thiopental (variable total doses of 15
      120 mg/kg) was added to the flush and given with reperfusion. In group 3 (n=7),
      thiopental (15 or 45 mg/kg) plus phenytoin (10, 20, or 30 mg/kg) was given by
      flush and with reperfusion. Outcome was assessed in terms of overall performance
      categories (OPC 1, normal; 2, moderate disability; 3, severe disability; 4, coma;
      5, brain death), neurologic deficit scores (NDS 0-10%, normal; 100%, brain
      death), and histologic deficit scores (HDS, total and regional). The flush
      reduced tympanic temperature to about 36 degrees C in all groups. In control
      group 1, one dog achieved OPC 1, three OPC 2, six OPC 3, and four OPC 4. In
      thiopental group 2, two dogs achieved OPC 1, two OPC 3, and five OPC 4. In
      thiopental/phenytoin group 3, one dog achieved OPC 1, two OPC 3, and four OPC 4
      (p=0.5). Median NDS were 36% (IQR 22-62%) in group 1; 51% (IQR 22-56%) in group
      2; and 55% (IQR 38-59%) in group 3 (p=0.7). Median total HDS were 67 (IQR 56-127)
      in group 1; 60 (IQR 52-138) in group 2; and 76 (IQR 48-132) in group 3 (p=1.0).
      Thiopental and thiopental/phenytoin dogs achieved significantly lower HDS only in
      the putamen. Thiopental in large doses caused side effects. We conclude that
      neither thiopental alone nor thiopental plus phenytoin by flush, with or without
      additional intravenous infusion, can consistently provide 'clinically
      significant' cerebral preservation for 20 min no-flow. Other drugs and drug
      combinations should be tested with this model in search for a breakthrough
      effect.

PMID- 11334696
TI  - CPR in terminally ill patients?
AB  - While limiting and foregoing therapy at the end of life is now accepted on
      medical, ethical, moral and legal grounds, many Americans continue to die with
      heroic measures being taken to prevent their death. When the patient does
      eventually die, attempts are frequently made to revive the patient by performing
      cardiopulmonary resuscitation (CPR). While CPR may result in the establishment of
      a perfusing pressure, in almost all instances, the patient succumbs despite
      advanced life support technology. The widespread adoption of do-not-resuscitate
      (DNR) protocols has not prevented CPR from being performed on patients, who are
      unlikely to survive. We present two cases, which highlight the modern American
      way of dying. We submit that poor end-of-life care may result from physicians
      discomfort with death, their poor communication skills and their failure to fully
      comprehend the benefits and limitations of advanced life support technology.
      Furthermore, we maintain that CPR should only be performed on patients, who are
      likely to derive benefit from this intervention.

PMID- 11334697
TI  - PaCO(2)/ETCO(2) gradient: early indicator of thrombolysis efficacy in a massive
      pulmonary embolism.
AB  - End tidal CO(2) measurement may be helpful in detecting the efficacy of
      thrombolysis after a massive pulmonary embolism. We report the case of a 76-year
      old man with a massive pulmonary embolism, who required early intubation and
      mechanical ventilation. Thrombolysis with rtpA (total dosage: 60 mg) was
      initiated. During this procedure, clinical data, arterial blood gases and end
      tidal CO(2) with a capnograph were recorded. Before thrombolysis the P(a-ET)CO(2)
      gradient was raised to 25 mmHg. During thrombolysis, the clinical data improved
      and the P(a-ET) gradient fell to 14 mmHg. We postulate that the P(a-ET)CO(2)
      gradient seems to be a reasonable indicator of efficacy of thrombolysis in this
      setting. However, the gradient did not return to normal values (4-5 mmHg). The
      possible reasons for this may be that during mechanical ventilation there was a
      large ventilation-perfusion ratio and the cardiac output may have still reduced.
      With these limitations, we conclude that the P(a-ET)CO(2) gradient should be
      evaluated as an indicator of pulmonary reperfusion in massive pulmonary embolism.

PMID- 11334698
TI  - Prepulse effects as a function of cortical projection system.
AB  - A putative gating mechanism reduces startle blink, midline scalp potentials
      beginning with P50, and perceived loudness of startling stimuli. Tactile
      prestimuli were paired with auditory startle stimuli to determine if: (1) P50
      inhibition is due to an extrinsic mechanism, (2) pairing differentially affects
      potentials reflecting modality specific and nonspecific system activity, and (3)
      crossmodal pairing modifies perceptual magnitudes of both pair members. Stimuli
      were presented alone and in pairs separated by 60 or 360 ms. Event-related
      potentials (ERPs) were recorded from midline and lateral sites; EMG was recorded
      from several facial and scalp muscles. Pairing reduced blink, and midline P50,
      N100 and P200 amplitudes; reductions were greater at the longer interval. P30 was
      largely unaffected by pairing. Pairing also differentially affected lateral N100
      components reflecting later activity in specific and nonspecific systems. Results
      show that prestimulus inhibition of ERPs is not due to intrinsic refractoriness
      and that pairing differentially affects ERPs associated with modality specific
      and nonspecific projection systems.

PMID- 11334700
TI  - Analysis of twenty-four hour heart rate variability in patients with panic
      disorder.
AB  - Growing evidence suggests that alterations in autonomic function contribute to
      the pathophysiology of panic disorder (PD). This retrospective study employed 24
      h heart rate variability (HRV) analysis of Holter records to compare autonomic
      function in PD patients (n = 38) with healthy, age- and gender-matched controls.
      Both time and frequency domain measures were calculated, and a circadian rhythm
      analysis was performed. The SDNN index, 5-min total power, very low frequency
      (VLF) and low frequency (LF) power were significantly lower in panic patients
      relative to controls over the 24-h period. Hourly means were significantly lower
      during some of the waking hours as well as the latter part of the sleep cycle. In
      contrast, the mean RR interval, RMSSD and high frequency (HF) power were
      comparable in patients and controls. Results suggest that sympathetic activity is
      depressed in PD patients under usual life conditions, leading to a relative
      predominance of vagal tone. Findings of low HRV in PD patients are consistent
      with the high rate of cardiovascular morbidity and mortality in this population,
      as well as with the emerging view of panic as a disorder involving reduced
      flexibility and adaptability across biological, affective and behavioral
      dimensions.

PMID- 11334699
TI  - Attentional selection in the processing of hierarchical patterns: an ERP study.
AB  - The current study aimed to investigate the effect of attentional selection of
      distinctive local elements on the processing of hierarchically organized
      patterns. Event-related brain potentials (ERPs) were recorded from subjects
      during identifications of global or local shapes of hierarchical patterns where
      either all local elements were identical (homogeneous stimulus) or a local
      element closest to fixation was distinguished by color from others (pop-out
      stimulus). One group of subjects was presented with the homogeneous stimuli and
      required to identify global or local shapes in separate blocks of trials. The
      other group was presented with the pop-out stimuli and asked to attend to the
      unique local item in the local task. A global precedence effect was observed in
      behavioral data. ERPs showed enlarged posterior P1 and N2 amplitudes in the local
      relative to global conditions. Top-down attention to the pop-out item resulted in
      increased frontal/central N2 amplitudes in the local condition but eliminated the
      temporal/occipital N2 enhancement in the local relative to global conditions. Top
      down attention to the pop-out item also increased local-to-global interference in
      reaction times and frontal N2 latencies. The results suggest that a frontal
      mechanism is involved in directing top-down attention to a specific local item
      whereas a temporal/occipital mechanism is engaged in an attentional filtering
      process in the identification of local shapes in hierarchical analysis.

PMID- 11334701
TI  - Evidence for the application of rules in Pavlovian electrodermal conditioning
      with humans.
AB  - Two Pavlovian SCR conditioning experiments investigated interference effects in
      sequential training of positive and negative patterning discriminations in
      humans. In Experiment 1, positive patterning (A-, B-, AB+) was trained in Phase
      1, immediately followed by a negative patterning schedule (C+, D+, CD-). We
      predicted that human participants would learn a specific numerosity rule in
      positive patterning, which interferes with the subsequent negative patterning
      schedule. In Experiment 2, negative patterning (C+, D+, CD-) was trained in Phase
      1, followed by a positive patterning schedule (A-, B-, AB+) in Phase 2. Because
      human participants would learn an abstract 'separate-versus-together'- or
      'opposite'-rule to solve the negative patterning discrimination in Phase 1, there
      should be less interference in positive patterning in Phase 2 where the
      separate/together-rule could be applied, too. In both experiments, the initial
      patterning discriminations were acquired successfully. In Experiment 1, human
      participants totally failed to solve the Phase 2 discrimination, while in
      Experiment 2 appropriate response differentiation developed in Phase 2. Thus,
      without pre-experience human participants seem to utilize a specific numerosity
      rule in positive patterning and a separate/together-rule in negative patterning.

PMID- 11334702
TI  - Further evidence of joint time-place control of rats' behavior: results from an
      'open hopper' test.
AB  - Rats were trained on an interval time-place task. Food was intermittently
      available on each of four levers for 4 min in a 16-min session. After baseline
      training the rats received 'open hopper' sessions in which food was available on
      all levers for all of the 16-min sessions. Despite the absence of any
      contingencies for doing so, the rats continued to press the levers in the
      'correct' sequence, for roughly the 'correct' amount of time. This confirms that
      the rat behavior was controlled, in part, by a representation of an elapsed
      interval of time. The rats responding was more variable in 'open hopper' sessions
      and error increased (in an exponential fashion) as the session proceeded. This
      finding suggests that the rats may have used shifts in the location of food
      availability to minimize the accumulation of error throughout baseline sessions.

PMID- 11334703
TI  - Exploratory patterns of rats on a complex maze provide evidence for topological
      coding.
AB  - Rats' exploratory patterns on a complex elevated maze were analyzed in both light
      and dark conditions. Rats were less active in the light than in the dark. In the
      light, they spent more time exploring the outer areas of the maze than the inner
      areas whereas exploration of both regions was similar in the dark. In both light
      and dark, rats spent more time investigating choice points (which provided
      multiple directions for movements) than runways that allowed only simple
      movements. In addition, choice points that provided more connections with other
      distant places were associated with more exploration. While such effects might be
      the result of stimulus-seeking of distant information in the light, increased
      exploration times in the dark presumably reflect the processing of local
      information associated with the maze connectivity. These results suggest that
      exploratory patterns in the dark reflect processing of the topological structure
      of the maze.

PMID- 11334704
TI  - Superstitious responding and reinforcement rate under concurrent variable
      interval extinction schedules.
AB  - To examine superstitious responding, four pigeons key pecked under multiple
      concurrent variable-interval 45 s variable-interval 90 s concurrent variable
      interval 90 s variable-interval 180 s schedules in the absence of a changeover
      delay. The two variable-interval 90 s schedules then were replaced by extinction,
      and key-peck responding during extinction was examined as a function of the
      prevailing reinforcement rate. During the first several sessions, extinction-key
      responding was maintained closer to baseline levels in the presence of the higher
      reinforcement rate, and this effect dissipated or even reversed with continued
      exposure to extinction. Although extinction-key responding generally decreased to
      near-zero levels after several sessions, in a few instances, it continued for 30
      and 45 sessions. These results demonstrate how concurrent variable-interval
      extinction schedules can be used to investigate what often has been labeled
      superstitious responding.

PMID- 11334705
TI  - Transitional choice behavior in concurrent-chain schedules.
AB  - The choice responses of four pigeons were examined in 20 periods of transition in
      a concurrent-chain procedure with variable-interval schedules as initial links
      and fixed delays to reinforcement as terminal links. In some conditions, the
      delays to reinforcement were different for the two terminal links, and changes in
      preference were recorded after the delays for the two response keys were
      switched. In other conditions, the reinforcer delays were equal for the two keys,
      but which key delivered 80% of the reinforcers was periodically switched. Choice
      proportions changed more quickly after a switch in reinforcement percentages than
      after a switch in the delays, thereby contradicting the hypothesis that faster
      changes would occur when the switch in conditions was easier to discriminate.
      Analyses of response sequences showed that the effects of individual reinforcers
      were larger and lasted longer in conditions with changing reinforcement
      percentages than in conditions with changing terminal-link delays. Rates of
      change in choice behavior do not appear to be limited by the unpredictability of
      variable reinforcement schedules, because the changes in behavior were slow and
      gradual even when there was a large and sudden change in reinforcer delays.

PMID- 11334706
TI  - Mirror image processing in three marine mammal species: killer whales (Orcinus
      orca), false killer whales (Pseudorca crassidens) and California sea lions
      (Zalophus californianus).
AB  - Dolphins (Tursiops truncatus) and their relatives might be expected to show
      mirror-induced contingency checking, a prerequisite to self-recognition, because
      of their high brain development, their complex social life and their demonstrated
      abilities in bodily imitation. A study of killer whales'(Orcinus orca) behaviour
      in front of a mirror is presented, including a mark test. Shorter investigations
      of mirror behaviour are also described in false killer whales (Pseudorca
      crassidens) and California sea lions (Zalophus californianus). Contingency
      checking was present in killer whales and possibly also in false killer whales,
      but no clear contingency checking was observed in sea lions. The mark test on
      killer whales suggested that the marked animal anticipated that its image would
      look different. This study shows that killer whales and false killer whales, like
      bottlenose dolphins, appear to possess the cognitive abilities required for self
      recognition.

PMID- 11334707
TI  - Acquisition of discriminations involving ambiguous or non-ambiguous features: an
      evaluation of two configural learning models.
AB  - The present rat experiment evaluated the validity of two formal accounts of
      configural learning in the framework of discrimination tasks involving the serial
      presentation of feature and target stimuli: Rescorla's (1973) modification of the
      Rescorla-Wagner model (1972) and the Pearce model (1987). The first, ambiguous
      feature task was of the form X-->A+, Y-->A-, X-->B-, Y-->B+, in which X and Y
      represent visual features, '-->' signifies a serial arrangement, A and B are
      auditory target stimuli, and '+' and '-' symbolise food-reinforcement and non
      reinforcement, respectively. The second, non-ambiguous feature task was of the
      form: X-->A+, Y-->A-, X-->B+, Y-->B-. The former task was much more difficult to
      solve than was the latter task. The Rescorla model is able to account for the
      observed differences between the two tasks in learning rates and in the
      associative strength of feature X with more plausible parameter values than is
      the Pearce model. It is suggested that models acknowledging a role for both
      elemental and configural learning can better account for discrimination learning
      in discrimination tasks of the sort presented in this study than do models that
      exclusively allow for configural learning.

PMID- 11334708
TI  - Maternal selectivity suppression through peripheral anosmia affects neither
      overall nursing frequency and duration, nor lactation performance in ewes.
AB  - The effects of prepartum peripheral anosmia on nursing activity, milk production
      and growth of the lambs, were assessed by comparing intact (n=10) and anosmic
      (n=10) multiparous Columbia and Rambouillet ewes and their single lamb during the
      first 2 months of lactation. Intact mothers only nursed their own lamb (98%)
      while most of the nursing activity in anosmic mothers concerned alien lambs
      (78%). On the other hand, the total duration and the frequencies of nursing did
      not differ significantly between groups (P>0.05). Nevertheless, the total
      percentage of nursing of own lamb by anosmic mothers (22%) was higher than
      expected at random (10%). Milk production or lambs' weights did not differ
      between groups. We conclude that prepartum anosmia resulted in the failure of
      ewes to develop true selective nursing up to the 8th week of lactation, although
      some preferential mother-young relationship yet developed. On the other hand, it
      did not affect significantly overall nursing activity.

PMID- 11334709
TI  - Synthesis and structural organization of zonular fibers during development and
      aging.
AB  - Zonular fibers are a specific form of extracellular matrix composed mainly of
      fibrillins. The purpose of this study was to determine which cells secrete
      fibrillin-1 during development and aging. A specific guinea pig fibrillin-1 mRNA
      probe was designed and cloned in order to identify fibrillin-secreting cells in
      guinea pig eye, using in situ hybridization. Immunofluorescence, with a specific
      guinea pig monoclonal antibody, was used to compare protein levels at different
      stages from birth to 35 months of age. Electron microscopy and immunolabeling
      were used to investigate the organization of zonular microfibril bundles. We
      identified the cells of non-pigmented epithelium of the ciliary body as the main
      source of fibrillin secreted into the zonule. Moreover, while mRNA expression
      decreased during aging, there was no decrease in fibrillin immunoreactivity, as
      previously described in human aorta. These data indicate a very slow turnover of
      the zonular microfibrils which can be correlated with the appearance during aging
      of a new periodic fibrillar structure. This new structure may reflect an
      increased cross-linking in the long-lived zonular microfibrillar bundles.

PMID- 11334710
TI  - Metalloproteinase activity in growth plate chondrocyte cultures is regulated by
      1,25-(OH)(2)D(3) and 24,25-(OH)(2)D(3) and mediated through protein kinase C.
AB  - During endochondral development, growth plate chondrocytes must remodel their
      matrix in a number of ways as they differentiate and mature. In previous studies,
      we have shown that matrix metalloproteinases (MMPs) extracted from matrix
      vesicles can extensively degrade aggrecan and that this is modulated by vitamin D
      metabolites in a manner involving protein kinase C (PKC). Matrix vesicles
      represent only a small component of the extracellular matrix, however, and it is
      unknown if the total metalloproteinase complement, including the MMPs and
      aggrecanases in the culture, is also regulated in a similar way. This study
      tested the hypothesis that vitamin D metabolites regulate the level of
      metalloproteinase activity in growth plate chondrocytes via a PKC-dependent
      mechanism and play a role in partitioning this proteinase activity between the
      media and cell layer (cells+matrix) in these cultures. To do this, resting zone
      cells (RC) were treated with 10(-9)-10(-7) M 24R,25-(OH)(2)D(3), while growth
      zone cells (GC) were treated with 10(-10)-10(-8) M 1alpha,25-(OH)(2)D(3).
      Cultures of both cell types were also treated with the PKC inhibitor
      chelerythrine in the presence and absence of vitamin D metabolites. At harvest,
      the media were either left untreated or treated to destroy metalloproteinase
      inhibitors, while enzyme activity in the cell layers was extracted with buffered
      guanidine and then treated like the media to destroy metalloproteinase
      inhibitors. Neutral metalloproteinase (aggrecan-degrading activity) activity was
      assayed on aggrecan-containing polyacrylamide gel beads and collagenase activity
      was measured on telopeptide-free type I collagen. Neutral metalloproteinase
      activity was found primarily in the cell layer of both cell types; however,
      activity was greater in extracts of GC cell layers. No collagenase activity could
      be detected in RC extracts until the metalloproteinase inhibitors were destroyed.
      In contrast, extracts of GC cell layers contained measurable activity without
      removing the inhibitors, and destroying the inhibitors resulted in a greater than
      two-fold increase in activity. No collagenase activity was found in the media of
      either cell type. 24,25-(OH)(2)D(3) caused a dose-dependent increase in neutral
      metalloproteinase activity in extracts of RC cells, but had no effect on
      collagenase activity. In contrast, 1,25-(OH)(2)D(3) caused a dose-dependent
      decrease in collagenase activity in extracts of GC cells, but had no effect on
      neutral metalloproteinase activity. In both cases, the effect of the vitamin D
      metabolite was mediated through the activation of PKC. These results support the
      hypothesis that metalloproteinases are involved in regulating the bulk turnover
      of collagen and aggrecan in growth plate chondrocytes and that the amount of
      metalloproteinase activity found is a function of the cell maturation state.
      Furthermore, 83-93% of neutral metalloproteinase activity and 100% of collagenase
      activity is localized to the cell layer. Moreover, the regulation of
      metalloproteinase activity by 1,25-(OH)(2)D(3) and 24,25-(OH)(2)D(3) involves a
      PKC-dependent pathway that is controlled by the target cell-specific vitamin D
      metabolite.

PMID- 11334711
TI  - Vitamin C-sulfate inhibits mineralization in chondrocyte cultures: a caveat.
AB  - Differentiating chick limb-bud mesenchymal cell micro-mass cultures routinely
      mineralize in the presence of 10% fetal calf serum, antibiotics, 4 mM inorganic
      phosphate (or 2.5 mM beta-glycerophosphate), 0.3 mg/ml glutamine and either 25
      microg/ml vitamin C or 5-12 microg/ml vitamin C-sulfate. The failure of these
      cultures to produce a mineralized matrix (assessed by electron microscopy, 45Ca
      uptake and Fourier transform infrared microscopy) led to the evaluation of each
      of these additives. We report here that the "stable" vitamin C-sulfate (ascorbic
      acid-2-sulfate) causes increased sulfate incorporation into the cartilage matrix.
      Furthermore, the release of sulfate from the vitamin C derivative appears to be
      responsible for the inhibition of mineral deposition, as demonstrated in cultures
      with equimolar amounts of vitamin C and sodium sulfate.

PMID- 11334712
TI  - Extracellular matrix in development of the intervertebral disc.
AB  - Intervertebral discs allow bending and twisting of the spine whilst resisting
      compression from gravity and muscle action, and are composite structures of the
      peripheral annulus fibrosus enclosing the nucleus pulposus. Their development is
      complex, involving several different connective tissue types, yet little is known
      of the developing extracellular matrix (ECM). We report the ECM composition of
      foetal rat discs from their first appearance to birth. The earliest collagen
      detected was type III, which was subsequently replaced by type II in the
      cartilaginous inner annulus and joined by type I in the fibrous outer annulus.
      Type IV collagen appeared in outer annulus, associated with myofibroblast-like
      cells of the orienting collagenous lamellae. Laminin and fibronectin co
      distributed here in later stages, although overall they had a wider distribution.
      Aggrecan occurred in early nucleus pulposus and then appeared in the inner
      annulus, in association with cartilage differentiation. Versican appeared later
      in the inner annulus, and also in the dorsal region of the outer annulus.
      Comparisons of glycosaminoglycan and proteoglycan label allowed extrapolations to
      be made as to likely glycosaminoglycan components of the large proteoglycans, and
      of other proteoglycans that may be present - thus differential distribution of
      aggrecan and keratan sulfate label suggested the presence of fibromodulin and/or
      lumican. Functionally aggrecan would confer compression resistance to
      cartilaginous structures. Versican may also contribute, but along with the small
      proteoglycans is likely to be associated with various stages of control of cell
      differentiation, tissue morphogenesis and collagen fibre formation in the
      assembly of the annulus fibrosus.

PMID- 11334713
TI  - Induction of periosteal callus formation by bone morphogenetic protein-2
      employing adenovirus-mediated gene delivery.
AB  - Although the chondrogenic response of periosteum is well established in healing
      fractures, the mechanisms mediating the proliferation and differentiation of
      periosteal chondroprogenitor cells are poorly understood. In the present study we
      demonstrate that bone morphogenetic protein-2 (BMP-2), introduced by adenovirus
      mediated gene transfer, alone is capable of inducing callus formation at the site
      of periosteal injection. Both immunohistochemistry and Northern analysis
      demonstrated activation of type II collagen production between days 4 and 7 after
      the injection, followed by activation of type X collagen expression. The
      activation of chondrogenesis was associated with increased expression of L-Sox5
      and Sox9, suggesting that the BMP-2 effect is mediated via Sox proteins. This
      capacity of adenovirus-mediated overproduction of BMP-2 to induce chondrogenesis
      (and subsequent endochondral ossification) should be useful for tissue
      engineering of cartilage and bone.

PMID- 11334714
TI  - Renomedullary interstitial cells in culture; the osmolality and oxygen tension
      influence the extracellular amounts of hyaluronan and cellular expression of
      CD44.
AB  - Our previous studies have suggested a role for renomedullary interstitial cells
      (RMICs) and renal medullary hyaluronan (HA) in water homeostasis. In the present
      study, cultured rat RMICs were used to examine the relationship of osmolality and
      oxygen tension on the extracellular amount of HA in the culture and to the
      cellular immunoreactivity to CD44, a HA binding protein. Under isotonic (330
      mOsm(.)kg(-1) H(2)O), normoxic (20% O(2)) conditions, supernatant from sub
      confluent RMICs contained 120+/-37 pg 10(4) cells(-1) 24 h(-1) of HA. Under
      hyperosmotic conditions (630 mOsm kg(-1) H(2)O), HA in the supernatant was
      decreased by 42% and under hypoosmotic conditions (230 mOsm kg(-1) H(2)O) it was
      doubled. Under hypoxic, iso-osmolar conditions (5% and 1% O(2), 330 mOsm kg(-1)
      H(2)O) this HA content was decreased by 56 and 48%, respectively, compared with
      normoxic, iso-osmolal conditions. Expression of CD44 on sub-confluent cells
      increased with increasing osmolality, as shown by immunostaining and flow
      cytometric analysis. The increases in CD44 from 330 to 630, 930 and 1230 mOsm kg(
      1) H(2)O amounted to 5, 142 and 212%, respectively. Low oxygen tension (5% O(2))
      decreased the intensity of CD44 immunofluorescence by 31%. Cell viability was
      similar at all conditions studied. In summary, these data indicate that cultured
      RMICs produce HA and are immunoreactive to CD44. In the supernatant of RMICs, the
      HA content decreases under hyperosmotic, hypoxic conditions. Conversely, CD44
      immunoreactivity increases under hyperosmotic conditions. These results may
      explain our previous in vivo findings of a decreased renal papillary HA content
      during anti-diuresis and an increased content during water diuresis. The results
      support the concept that RMICs play an important role in renal water handling.

PMID- 11334715
TI  - Complete genomic structure of mouse lysyl hydroxylase 2 and lysyl hydroxylase
      3/collagen glucosyltransferase.
AB  - Lysyl hydroxylase is an enzyme involved in collagen biosynthesis, catalyzing the
      hydroxylation of lysyl residues as a post-translational event. Three isoforms
      have been characterized so far (LH1, LH2, LH3). Our recent findings indicate that
      LH3 possesses, not only lysyl hydroxylase activity, but also
      galactosylhydroxylysyl glucosyltransferase activity [Heikkinen et al., J. Biol.
      Chem. 275 (2000) 36158-36163]. We report here the characterization of mouse LH2
      (Plod2) and LH3/glucosyltransferase (Plod3) genes. Plod2 spans approximately 50
      kb of the genomic DNA, and is organized in 20 exons, one of the exons being
      alternatively spliced in the RNA processing. Plod3 spans approximately 10 kb of
      the genomic DNA, and contains 19 exons. Analysis of the 5' flanking region with
      many transcription start sites reveals the lack of a TATAA box in both genes.
      Sequence analysis indicated many retroposon-like elements within the Plod3 gene.
      A comparison was carried out among the LH1, LH2 and LH3 gene structures
      characterized so far from different species.

PMID- 11334716
TI  - Expression of frizzled genes in mouse costochondral chondrocytes.
AB  - Protein products of frizzled genes are cell membrane receptors for Wnt proteins
      that play multiple roles during development. We examined the expression of nine
      frizzled genes in mouse chondrocytes, and detected transcripts of six of the nine
      genes. We also cloned the entire cDNA of mouse frizzled-1 and compared its cDNA
      sequence and the cysteine-rich and transmembrane domains of its translated
      product to sequences of frizzled-1 from C. elegans, Drosophila, chicken and
      human. We used the T31 Mouse/Hamster radiation hybrid panel to map the mouse
      frizzled-1 to mouse chromosome 5 (5 cM from the centromere), and frizzled-9 to
      mouse chromosome 5 (74 cM from the centromere).

PMID- 11334717
TI  - Cloning and characterization of a human lysyl oxidase-like 3 gene (hLOXL3).
AB  - Using the PCR primers generated from human expressed sequence tag (EST), the cDNA
      of lysyl oxidase-like gene 3 (LOXL3), a new member of human lysyl oxidases gene
      family, was cloned from the human fetal brain mRNA. The predicted amino acid
      sequence of the hLOXL3 gene was highly homologous to mLOR2. Bioinformatics
      analysis shows that hLOXL3 protein is also a member of the scavenger receptor
      cysteine-rich family, which contains a 25 amino acids signal peptide. The hLOXL3
      gene was mapped to human 2p13 locus by BLAST search and at least 14 exons were
      found. Expression of the hLOXL3 gene was detected in several human tissues and
      especially high in spleen and testis.

PMID- 11334718
TI  - Thyroid cancer following Chernobyl.

PMID- 11334719
TI  - Diet and cancer prevention.
AB  - Research from several sources provides strong evidence that vegetables, fruits,
      and whole grains, dietary fibre, certain micronutrients, some fatty acids and
      physical activity protect against some cancers. In contrast, other factors, such
      as obesity, alcohol, some fatty acids and food preparation methods may increase
      risks. Unravelling the multitude of plausible mechanisms for the effects of
      dietary factors on cancer risk will likely necessitate that nutrition research
      moves beyond traditional epidemiological and metabolic studies. Nutritional
      sciences must build on recent advances in molecular biology and genetics to move
      the discipline from being largely 'observational' to focusing on 'cause and
      effect'. Such basic research is fundamental to cancer prevention strategies that
      incorporate effective dietary interventions for target populations.

PMID- 11334720
TI  - Development of an EORTC disease-specific quality of life module for use in
      patients with gastric cancer.
AB  - Quality of life (QL) is an important outcome in clinical trials in oncology.
      There is currently no valid international QL measure for gastric cancer. This
      paper describes the development of a QL module for gastric cancer to supplement
      the European Organization for Research and Treatment of Cancer (EORTC) Quality of
      life (QLQ-C30) questionnaire. Phases I to III of module development were
      conducted in the United Kingdom, France, Germany and Spain according to EORTC QL
      Group guidelines. Twenty relevant QL issues were generated from the literature
      and interviews with health professionals (n=24) and patients (n=58). This
      produced a 24 item provisional module. Further testing in 115 patients resulted
      in the QLQ-STO22, containing 22 questions, conceptualised into five scales and
      four single items, related to disease symptoms, treatment side-effects and
      emotional issues specific to gastric cancer. The use of the QLQ-C30 supplemented
      by the QLQ-STO22 will provide a comprehensive QL measure for international trials
      in gastric cancer.

PMID- 11334721
TI  - Gemcitabine and vinorelbine as second-line therapy in non-small-cell lung cancer
      after prior treatment with taxane+platinum-based regimens.
AB  - Treatment options in patients with recurrent non-small-cell lung cancer (NSCLC)
      remain limited as a result of the poor activity of older agents after platinum
      based therapy. The present phase II study aimed to evaluate the combination of
      gemcitabine and vinorelbine in patients with relapsed NSCLC after pretreatment
      with taxane+platinum-based regimens, since gemcitabine has demonstrated activity
      in that setting and the combination has been well tolerated in previous phase
      I/II studies. Patients with advanced NSCLC (stages III/IV), World Health
      Organization (WHO), Performance Status (PS) < or = 2, prior platinum+taxane-based
      chemotherapy and unimpaired haematopoietic and organ function were eligible.
      Chemotherapy was administered as follows: vinorelbine 25 mg/m(2) followed by
      gemcitabine 1000 mg/m(2), both administered on days 1 and 8, recycled every 3
      weeks. 40 patients were entered and 39 were evaluable for response and all 40 for
      toxicity: median age was 61 years (range 50-72 years), median PS=1 (range 0-2),
      gender ratio=37 males/3 females, stages at initial diagnoses were IIIA=2,
      IIIB=14, IV=24. Metastatic sites included: lymph nodes: 23, bone: 4, liver: 5,
      brain: 4, lung nodules: 9, adrenals: 8, pleural effusion: 4. 22 patients had
      prior paclitaxel/ifosfamide/cisplatin treatment. Objective responses were;
      partial response (PR): 9/40 (22.5%), stable disease (SD): 13/40 (32.5%) and
      progressive disease (PD) 18/40 (45%). The median time-to-progression (TTP) was
      4.5 months (range 1-17 months) and median survival 7 months (range 2-17+ months).
      1-year survival was 17%. Grade 3 neutropenia was seen in 33% of patients. There
      was no grade 4 neutropenia and no episodes of febrile neutropenia. No grade 3/4
      thrombocytopenia or grade 3/4 other non-haematological toxicities were observed.
      The combination of gemcitabine/vinorelbine is active and well tolerated in
      patients with advanced NSCLC failing prior taxane/platinum therapy. This regimen
      represents a tolerable and effective combination to apply in the palliative
      treatment of relapsed NSCLC.

PMID- 11334722
TI  - Extensive cytoreductive surgery followed by intra-operative hyperthermic
      intraperitoneal chemotherapy with mitomycin-C in patients with peritoneal
      carcinomatosis of colorectal origin.
AB  - Peritoneal seeding from colorectal cancer has a very poor prognosis and is
      relatively resistant to systemic chemotherapy. We performed a phase I/II trial to
      investigate the feasibility and effectiveness of extensive cytoreductive surgery
      in combination with intra-operative hyperthermic intraperitoneal chemotherapy
      (HIPEC) in these patients. 29 patients with peritoneal carcinomatosis of
      colorectal origin without evidence of distant metastases underwent cytoreductive
      surgery and intra-operative HIPEC with mitomycin-C (MMC), followed by systemic
      chemotherapy with 5-fluorouracil (5-FU)/leucovorin. Surgical complications
      occurred in 11 patients (38%). One patient died directly related to the
      treatment, resulting in a mortality rate of 3%. MMC toxicity existed mainly of
      leucocytopenia (in 15 patients; 52%). After a median follow-up of 38 months
      (range 26-52 months) we found a 2- and 3-year survival rate (Kaplan-Meier) of 45
      and 23%, respectively. Extensive cytoreductive surgery and HIPEC is feasible in
      patients with peritoneal seeding of colorectal cancer. First results suggest that
      a higher median survival could be achieved compared with conventional palliative
      surgery and systemic chemotherapy, therefore a randomised phase III study is now
      being conducted.

PMID- 11334723
TI  - Value and cost evaluation of routine follow-up for patients with clinical stage
      I/II endometrial cancer.
AB  - The aim of the study was to determine the value and the costs of routine follow
      up for the detection of recurrences in patients treated for endometrial cancer.
      Between 1986 and 1995, 390 women with clinical stage I/II endometrial carcinoma
      were treated with combined surgery-radiation therapy. After treatment, follow-up
      was based on the clinical examination, a systematic Papanicolaou (Pap) smear and
      radiography (chest X-ray and abdomino-pelvic ultrasonography). 27 patients
      relapsed: 22 patients had symptoms and 5 were asymptomatic. None of the patients
      had recurrence detected on the routine Pap smear nor on the systematic chest X
      ray. In conclusion, the follow-up of patients treated for endometrial cancer
      based on routine Pap smears and systematic radiography does not permit earlier
      detection of recurrences. Follow-up should simply include a clinical examination
      whose frequency should be based on prognostic factors. Approximately two-thirds
      of this cost was due to systematic examinations (Pap smears and radiography). Our
      results indicate that such expenditure could be avoided.

PMID- 11334724
TI  - Risk, severity and predictors of physical and psychological morbidity after
      axillary lymph node dissection for breast cancer.
AB  - The aim of this study was to investigate the nature and severity of the arm
      complaints among breast cancer patients after axillary lymph node dissection
      (ALND) and to study the effects of this treatment-related morbidity on daily life
      and well-being. 400 women, who underwent ALND as part of breast cancer surgery,
      filled out a treatment-specific quality of life questionnaire. The mean time
      since ALND was 4.7 years (range 0.3-28 years). More than 20% of patients reported
      pain, numbness, or loss of strength and 9% reported severe oedema. None of the
      complaints appeared to diminish over time. Irradiation of the axilla and
      supraclavicular irradiation were associated with a 3.57-fold higher risk of
      oedema (odds ratio (OR) 3.57; 95% confidence interval (CI) 1.66-7.69) causing
      many patients to give up leisure activities or sport. Women who underwent
      irradiation of the breast or chest wall more often reported to have a sensitive
      scar than women who did not receive radiotherapy. Women <45 years of age had an
      approximately 6 times higher risk of numbness of the arm (OR 6.49; 95% CI 2.58
      16.38) compared with those > or = 65 years of age; they also encountered more
      problems doing their household chores. The results of the present study support
      the introduction of less invasive techniques for the staging of the axilla,
      sentinel node biopsy being the most promising.

PMID- 11334725
TI  - High-dose intensity oxaliplatin added to the simplified bimonthly leucovorin and
      5-fluorouracil regimen as second-line therapy for metastatic colorectal cancer
      (FOLFOX 7).
AB  - This phase II study examined a regimen (FOLFOX7) of leucovorin (LV), high-dose
      intensity oxaliplatin, and 5-fluorouracil (5-FU), as second-line therapy for
      metastatic colorectal cancer. 48 patients were enrolled - 36 refractory and 12
      resistant to prior therapy with LV-5-FU. Oxaliplatin (130 mg/m2) was infused with
      LV (400 mg/m2) over 2 h on day 1, followed by bolus 400 mg/m2 and a 46-h infusion
      (2400 g/m2) of 5-FU, every 2 weeks. Patients who responded or were stable
      received eight cycles. Patients were evaluated every 2 months. 20 patients (42%)
      had partial responses (95% confidence interval (CI): 28-56%), 19 (40%) had stable
      disease and 9 (19%) progressed. Median progression-free survival (PFS) was 6
      months and median survival 16.1 months. Toxic effects of National Cancer
      Institute-Common Toxicity Criteria (NCI-CTC) grade 3/4 were: peripheral
      neuropathy 15%, nausea 8%, diarrhoea 11%, neutropenia 9%, thrombocytopenia 11%.
      Overall, 38% of patients experienced grade 3/4 toxicities, and 64% received 90%
      or more of the scheduled oxaliplatin dose intensity during the first four cycles.
      FOLFOX7 was highly active, with good tolerability, in pretreated patients
      resistant to LV-5-FU [corrected].

PMID- 11334726
TI  - A randomised phase II study of oxaliplatin alone versus oxaliplatin combined with
      5-fluorouracil and folinic acid (Mayo Clinic regimen) in previously untreated
      metastatic colorectal cancer patients.
AB  - The aim of this study was to examine the efficacy and safety of both oxaliplatin
      as a single agent and oxaliplatin in combination with dailyx5 bolus 5
      fluorouracil and folinic acid (5-FU/FA, Mayo clinic regimen) in the first-line
      treatment of metastatic colorectal cancer (CRC) patients. 73 advanced CRC
      patients were randomised to receive either oxaliplatin 85 mg/m(2) every 2 weeks
      (35 patients), or the same treatment combined with 5-FU 425 mg/m(2)/day and FA 20
      mg/m(2)/dayx5 days every 4 weeks (38 patients). Treatment was continued until
      disease progression or unacceptable toxicity. All patients had documented
      inoperable disease and no previous chemotherapy for advanced disease. Based on
      the investigators' assessment of best response, objective response rate was 9%
      (95% confidence interval (CI) 2-24%) in the oxaliplatin arm, and 45% (95% CI 27
      64%) in the oxaliplatin+5-FU/FA arm. Median progression-free survival (PFS) was 2
      months (95% CI 1.7-2.4 months) in the oxaliplatin arm and 3.9 months (95% CI 2.9
      5 months) in the oxaliplatin+5-FU/FA arm. Severe neutropenia was seen in 23% of
      patients in the oxaliplatin+5-FU/FA arm, and none in the oxaliplatin arm. There
      were two treatment-related deaths, both in the oxaliplatin+5-FU/FA arm. In the
      oxaliplatin+5-FU/FA arm, severe diarrhoea, vomiting and stomatitis were seen in
      34, 14 and 14% of the patients, respectively. In conclusion, oxaliplatin at a
      dose of 85 mg/m(2) given every 2 weeks was well tolerated and has limited
      activity in metastatic CRC, while the combination of this treatment with the full
      dose Mayo clinic regimen (5-FU bolus 425 mg/m(2)/day+FA 20 mg/m(2)/dayx5 days
      every 4 weeks), although active, was unfeasible due to a high level of
      myelosuppression and gastrointestinal toxicity. Alternative lower dosing or other
      regimens are to be explored to ascertain the value of bolus 5-FU/FA combined with
      oxaliplatin.

PMID- 11334727
TI  - Antitumour activity of somatostatin analogues in progressive metastatic
      neuroendocrine tumours.
AB  - A few studies have suggested an antitumour activity of somatostatin analogues in
      neuroendocrine tumours (NET). The aim of this study was to evaluate the
      antitumour efficacy of somatostatin analogues in patients with documented
      progressive tumours. 35 consecutive patients with documented tumour progression
      were treated with somatostatin analogues. Patients were classified into two
      groups. In Group 1, tumours were progressing rapidly (an increase of 50% or more
      in the lesion surface area in 3 months) and in Group 2, tumours were progressing
      more slowly (an increase of less than 50% in the lesion surface area in 3 months
      but greater than 25% in 6 months). Treatment consisted of subcutaneous (s.c.)
      octreotide, 100 microg thrice daily for 17 patients, intramuscular lanreotide, 30
      mg/every 14 days for 11 patients and for 7 patients both somatostatin analogues
      were used successively during the follow-up. Primary tumour sites were the small
      intestine (n=12), pancreas (n=13), lungs (n=5), and other sites (n=5). 18
      patients had the carcinoid syndrome with flushing and/or diarrhoea. The median
      duration of treatment was 7 months. Treatment was discontinued in 3 patients due
      to side-effects. One patient (3%) achieved a partial response and the disease was
      stabilised in 20 patients (57%) for a median duration of 11 months (6-48 months).
      Stabilisation of patients in Group 1 was significantly less frequent at 6 months
      than that of patients in Group 2 (4/12 and 13/17 respectively, P<0.02).
      Somatostatin analogue treatment resulted in one partial response (3%) and 20
      cases of stabilisation (57%) in 35 patients with progressive NET. A slow tumour
      growth rate before treatment is predictive of a good response to somatostatin
      analogues which could be considered an option for first-line treatment.

PMID- 11334728
TI  - Thyroid cancer in children and young adults in the North of England. Is
      increasing incidence related to the Chernobyl accident?
AB  - Population-based data on thyroid carcinomas was obtained from the Northern Region
      Young Person's Malignant Disease Registry to analyse the incidence of thyroid
      cancers in young people (<25 years) in the North of England for the period 1968
      and 1997 and to assess if changes in incidence were consistent with the spatial
      and temporal distribution of the fallout from the Chernobyl nuclear accident. We
      compared incidence rates for differentiated (papillary or follicular) thyroid
      carcinomas 1968-1986 with those for 1987-1997. There were 75 cases of thyroid
      carcinoma diagnosed over the study period, of which 63 were differentiated
      carcinoma and 12 were medullary carcinoma. There were 26 young adults (15-24
      years) diagnosed with differentiated thyroid carcinoma in the 19-year period 1968
      1986 and 30 in the subsequent 11 years 1987-1997, Age standardised rate (ASR) 3.0
      versus 6.5, respectively (rate ratio 2.2, 95% confidence interval (CI): 1.3-3.6).
      There were three children (aged <15 years) diagnosed with differentiated
      carcinoma in the period 1968-1986 and four in the period 1987-1997, ASR 0.2
      versus 0.6 (rate ratio 2.7, 95% CI: 0.6-12.1). Regression models showed a
      significant increase in the incidence of thyroid cancer after the Chernobyl
      accident (P=0.002). In Cumbria, the area receiving the heaviest fallout in the
      UK, the increase in incidence was much greater (rate ratio 12.19, 95% CI 1.5
      101.2). These temporal and spatial changes in incidence are consistent with a
      causal association with the Chernobyl accident although a greater effect in the
      younger rather than the older age group would have been anticipated. However,
      factors including improvements in ascertainment and earlier detection of tumours
      may also have contributed to the increasing incidence. Further collaborative
      international studies are needed to investigate changes in the incidence of
      thyroid cancer in children and young adults.

PMID- 11334729
TI  - The BRCA1 syndrome and other inherited breast or breast-ovarian cancers in a
      Norwegian prospective series.
AB  - Inherited breast cancer is a heterogenous group of diseases. We examined this
      heterogeneity in a prospective series of inherited breast and ovarian cancers,
      previously demonstrated to include 84% of inherited cancers. Ninety-two tumours
      (65 breast and 27 ovarian) in 82 patients from 70 kindreds were prospectively
      diagnosed. Fifteen of the breast cancers were in situ, 50 were infiltrating. 40
      (49%) of the 82 women carried a BRCA1 mutation, whereas no mutation in BRCA2 was
      found. Approximately, two-thirds of the BRCA1 mutation carriers had one of the
      four most frequent Norwegian founder mutations. Ninety-five per cent of the
      epithelial ovarian cancers occurred in BRCA1 mutation carrying women versus 38%
      of infiltrating breast cancers and 7% of carcinoma in situ of the breast. The
      BRCA1 syndrome was phenotypically distinct with invasive, high grade, oestrogen
      receptor-negative breast cancers and epithelial ovarian cancers. Non-BRCA1/2
      inherited breast cancers included carcinoma in situ and lobular carcinoma and
      were frequently bilateral. Non-BRCA1/2 inherited breast cancer is not associated
      with epithelial ovarian cancer and in breast cancers has distinct biological
      characteristics, indicating that the different subgroups of inherited breast
      cancer may need different healthcare services.

PMID- 11334730
TI  - Expression of urokinase plasminogen activator and receptor in conjunction with
      the ets family and AP-1 complex transcription factors in high grade prostate
      cancers.
AB  - Expression of the urokinase plasminogen activator (uPA) and its receptor (uPAR)
      correlates with tumour cell invasiveness and helps to determine the prognosis of
      prostate and other cancers. The purpose of this study was to establish in
      prostate cancer, the ets family and AP-1 complex transcription factors that might
      activate the inducible AP-1 and AP-1/PEA3 elements of the uPA enhancer. uPA and
      uPAR were expressed preferentially in adenocarcinoma cells, but not the stroma of
      high grade prostate cancers. The ets family paralogues Fli-1 and Elf-1 were also
      highly expressed in adenocarcinoma cells of the majority of cancers, while Erg
      1,2 and Ets-2 were expressed in a minority of cancers and Elk-1, PEA3 and PU.1
      were minimally expressed. A minority of cancers expressed high levels of
      cytoplasmic and/or nuclear c-Jun and c-Fos transcription factors. We speculate as
      to the molecular basis for such expression.

PMID- 11334731
TI  - Selection with melphalan or paclitaxel (Taxol) yields variants with different
      patterns of multidrug resistance, integrin expression and in vitro invasiveness.
AB  - A melphalan-resistant variant (Roswell Park Memorial Institute (RPMI)-2650Ml) and
      a paclitaxel-resistant variant (RPMI-2650Tx) of the drug-sensitive human nasal
      carcinoma cell line, RPMI-2650, were established. The multidrug resistance (MDR)
      phenotype in the RPMI-2650Tx appeared to be P-glycoprotein (PgP)-mediated.
      Overexpression of multidrug resistant protein (MRP) family members was observed
      in the RPMI-2650Ml cells, which were also much more invasive in vitro than the
      parental cell line or the paclitaxel-resistant variant. Increased expression of
      alpha(2), alpha(5), alpha(6), beta(1) and beta(4) integrin subunits, decreased
      expression of alpha(4) integrin subunit, stronger adhesion to collagen type IV,
      laminin, fibronectin and matrigel, increased expression of MMP-2 and MMP-9 and
      significant motility compared with the parental cells were observed, along with a
      high invasiveness in the RPMI-2650Ml cells. Decreased expression of the alpha(2)
      integrin subunit, decreased attachment to collagen type IV, absence of
      cytokeratin 18 expression, no detectable expression of gelatin-degrading
      proteases and poor motility may be associated with the non-invasiveness of the
      RPMI-2650Tx variant. These results suggest that melphalan exposure can result in
      not only a MDR phenotype, but could also make cancer cells more invasive, whereas
      paclitaxel exposure resulted in MDR without increasing the in vitro invasiveness
      in the RPMI-2650 cells.

PMID- 11334732
TI  - A combination of interleukin-2 and 60 nm cationic supramolecular biovectors for
      the treatment of established tumours by subcutaneous or intranasal
      administration.
AB  - The Supramolecular Biovector (SMBV) KY is a drug delivery nanocarrier which
      consists of a discretely sized, ionically charged, cross-linked polysaccharide
      core surrounded by a lipid membrane. We used the non-immunogenic spontaneous
      mammary adenocarcinoma TS/A tumour to test the efficacy on tumour growth of low
      (10(4) IU) or ultra-low (10(3) IU) doses of interleukin-2 (IL-2) adsorbed to
      these 60 nm cationic synthetic particles. In comparison with the progressive
      growth of TS/A cells in syngeneic mice, KY/IL-2 particles coinjected with TS/A
      cells or administered at a distance from the tumour, inhibited tumour growth
      while free IL-2, even at 10-100 times the dose used in the KY/IL-2 formulations,
      had no effect. Studies performed on implanted tumours (treatment at day 6 (D6))
      showed that KY/IL-2 administered subcutaneously (s.c.) at five sites distant from
      the tumour (10(3) IL-2 IU per site) induced rejection of the implanted tumours.
      Six out of 10 mice were cured while the other four had residual tumours only. In
      the same experiment, free IL-2 induced only tumoral growth reduction. Protection
      induced by KY/IL-2 administered s.c. at five sites involved recruitment of a
      CD8(+) T cell response since nu/nu mice and CD8-depleted mice did not reject the
      tumours. Mice cured were protected significantly to completely against a
      rechallenge with TS/A tumour cells, and a systemic tumour-specific CTL activity
      was induced. Finally, we showed that repeated intranasal (i.n.) administration of
      KY/IL-2 (low-dose) also led to complete regression of pre-established tumours and
      partial protection from tumour rechallenge. We therefore suggest that, in
      contrast to free IL-2, a KY/IL-2 formulation could be used as a systemic
      immunostimulant leading to the eradication of non-immunogenic, established
      tumours.

PMID- 11334733
TI  - Chromatin condensation and sensitivity of DNA in situ to denaturation during cell
      cycle and apoptosis--a confocal microscopy study.
AB  - The goal of this study was to construct high resolution 3D confocal images of
      regions of condensed and extended chromatin in cell nuclei and individual
      chromosomes. It has been shown previously that sensitivity of DNA in situ to
      denaturation correlates with chromatin condensation and varies during cell cycle
      and apoptosis. Thus, detection of DNA which was partially denatured in situ
      provided a means to image areas of condensed chromatin. DNA denaturation was
      detected using a metachromatic dye acridine orange (AO) which differentially
      stains single stranded (ss) and double-stranded (ds) DNA sections. Early studies
      of denaturability of cellular DNA utilized flow cytometry and standard
      fluorescence microscopy. These techniques could not reveal small local
      differences in DNA denaturability within cell nucleus or in individual
      chromosomes. For instance, it was not possible to detect the initial points of
      chromosome condensation in G2-phase of the division cycle or in apoptosis. In
      order to achieve this goal we have recently extended these studies by applying
      confocal microscopy. We investigated DNA denaturability in normal human
      fibroblasts and HL-60 leukemic cells, at different stages of cell cycle and
      apoptosis. Following removal of RNA and partial denaturation of DNA with acid
      cells were stained with AO. Green (530 nm) and red (640 nm) fluorescence (exc.
      457 nm) of non-denatured and denatured DNA was imaged by confocal microscopy.
      Blind deconvolution was used to further improve the quality of 3D images.
      Photobleaching of AO fluorescence was minimized and a correction for chromatic
      aberration and register shift was implemented. Nuclei of interphase cells
      exhibited predominantly green fluorescence representing AO binding to ds DNA.
      Punctuate areas of red fluorescence representing AO binding to denatured DNA and
      most likely associated with local regions of condensed chromatin were also
      present in all interphase nuclei. The proportion of denatured DNA increased in
      cells entering mitosis. In prophase individual condensing chromosomes exhibited
      varied proportions of green and red fluorescence indicating different content of
      denatured chromatin. In some chromosomes bands of denatured and denaturation
      resistant chromatin were clearly resolved. In metaphase and anaphase chromosomes
      exhibited red fluorescence along all length of their arms indicating the highest
      and uniform susceptibility to denaturation. In telophase chromosomes contained
      predominantly denaturation-resistant DNA again and denaturated regions were
      significantly less abundant. At cytokinesis some decondensing chromosomes were
      still resolved. At this stage almost all regions of denatured DNA were located
      close to nuclear envelope. These regions may correspond to pockets of
      heterochromatin reforming at nuclear periphery. In early apoptosis condensation
      of chromatin appeared to commence in several distinct regions within nucleus.
      Some apoptotic bodies contained condensed chromatin surrounding central regions
      of extended chromatin. At late stages of apoptosis the whole volume of apoptotic
      bodies was occupied by condensed chromatin.

PMID- 11334734
TI  - Visualisation of mitochondria in living neurons with single- and two-photon
      fluorescence laser microscopy.
AB  - In this work we investigated the relative merits of conventional single-photon
      confocal laser scanning fluorescence microscopy (CLSM) and two-photon laser
      scanning fluorescence microscopy (2p-LSM) for the study of mitochondria in living
      neurons. Dorsal root ganglion neurons were loaded with the mitochondrion-specific
      fluorescent dye JC-1, the ratio between red (J-aggregates) and green (monomer)
      fluorescence of which reflects mitochondrial membrane potential. Cells were
      illuminated at 488 nm for single-photon excitation or at 870 nm for two-photon
      excitation. In both modalities we found that mitochondria showed: (i) similar
      appearance; (ii) similar fluorescence ratio values over both whole cell bodies
      and individual mitochondria; and (iii) similar responses to mitochondrial
      uncoupler, which dropped the ratio values by 50%. However, 2p-LSM exhibited
      several advantages over CLSM: (i) better signal/noise ratio in the green emission
      channel; (ii) less phototoxicity upon repetitive scanning in the focal plane; and
      (iii) no significant loss of image quality upon repetitive scans in the z
      direction. We conclude that, while both techniques enable visualisation of
      individual mitochondria in living cells, 2p-LSM has significant advantages for
      physiological work requiring time-lapse experiments or four-dimensional
      reconstructions of mitochondria.

PMID- 11334735
TI  - Multi-photon fluorescence microscopy--the response of plant cells to high
      intensity illumination.
AB  - Multi-photon fluorescence microscopy has been cited for its advantage in
      increased depth penetration due to low linear absorption and scattering
      coefficient of biological specimen in the near infrared (NIR) range. Because of
      the need of high peak power for efficiently exciting two-photon fluorescence, the
      relationship between cell damage and peak power has become an interesting and
      much debated topic in the applications of multi-photon fluorescence microscopy.
      It is conceivable that at high illumination intensity, non-linear photochemical
      processes have impacts on cell physiology and viability in ways much different
      from low illumination in the linear domain. In this article, we discuss some of
      the issues in two-photon fluorescence microscopy, including the degree of
      transparency of the specimen, a comparison of single- and two-photon excited
      fluorescence spectra, and the cell damage under high intensity illumination,
      using plant cells as a model.

PMID- 11334736
TI  - A gamma-tubulin antibody against a plant peptide sequence localises to cell
      division-specific microtubule arrays and organelles in plants.
AB  - Gamma tubulin (gamma-tubulin) is involved in microtubule initiation in the
      eukaryotes. In animal cells it is localised to centrosomes and to other, non
      centrosomal sites of microtubule initiation. In addition, cytoplasmic complexes
      containing gamma-tubulin (gamma-TuRCs; gamma-somes) have been described, which
      are multiprotein complexes involved in microtubule initiation. Most localisations
      of gamma-tubulin in plants have previously been achieved using an antibody
      directed towards a conserved peptide sequence found in animal cells, showing co
      localisation with all microtubule arrays throughout the cell cycle. Because
      different antibodies may give various patterns of subcellular localisation, in
      the present study we raised a polyclonal antibody ('Hayley') to the plant peptide
      sequence EDFATQGGDRKDVFFY (bold letters indicate plant-specific amino acids) to
      further investigate the subcellular distribution in plants. Immunoblotting using
      wheat root tip protein extracts revealed a 58 kDagamma-tubulin-like peptide as
      has been described before. Immunofluorescence microscopy of wheat root-tip cells,
      however, revealed localisation of gamma-tubulin to a subset of mitotic
      microtubule arrays and the cytokinetic phragmoplast, but not to interphase
      cortical arrays or the preprophase band of microtubules. This lack of labelling
      may be caused by a restriction of antibody access during interphase, but more
      likely by a cell division-specific conformational change in the gamma-tubulin
      molecule. Our antibody also gave an organelle-like labelling, not described
      before, which may represent storage forms or precursors of gamma-tubulin, perhaps
      related to plastid-based microtubule initiation in hepatics and hornworts.

PMID- 11334737
TI  - Visualization of meiotic events in intact living anthers by means of two-photon
      microscopy.
AB  - In this paper we describe the application of two-photon microscopy (2 PM) to the
      study of meiosis in plants. Fresh, unfixed anthers of Agapanthus umbelatus were
      briefly incubated on a minimal medium containing the DNA fluorophore DAPI. DAPI
      incorporation took place in about 30 min and nuclei and other DNA-containing
      organelles kept their fluorescence for more than 24 h. Using PM it was possible
      to optically section the whole, unfixed anthers to a depth of approximately 200
      microm. This was up to the mid sagital section and into the sporogenic tissue.
      Several meiotic figures were observed with unparalleled resolution. Sequences of
      nuclear dynamics and division were occasionally observed in the surrounding
      tissues and epidermal layer of cells. However we could not optimize the
      procedures up to the level of observing the dynamics of division on the meiotic
      nuclei as well. We hypothesize that either (1) meiotic cells are sensitive to the
      reasonably high excitation levels of infrared light needed to attain such
      penetration in the tissue, or (2) that our incubation procedures are not
      sufficiently non-invasive for meiosis to remain unperturbed. To the best of our
      knowledge this is the first report on direct observation of living meiotic cells
      in plants and establishes the potential of 2 PM for intact organ research.

PMID- 11334738
TI  - Simultaneous multichannel nonlinear imaging: combined two-photon excited
      fluorescence and second-harmonic generation microscopy.
AB  - Simultaneous two-photon excited fluorescence (TPF) and second-harmonic generation
      (SHG) imaging is demonstrated using a single femtosecond laser and a scanning
      microscope. This composite nonlinear microscopic technique was applied to imaging
      DNA and chromosomes, and it was shown that the two different interaction
      mechanisms provide complementary information on the structure and nonlinear
      properties of these biological materials, beyond that achievable using either TPF
      or SHG imaging alone. The use of separate modes of detection, in reflection and
      transmission respectively, and the simultaneous nature of the acquisition of the
      two images allows pure TPF and SHG images in precise registration to be obtained.

PMID- 11334739
TI  - Optimization of second-harmonic generation microscopy.
AB  - We describe the principles and characteristics of second-harmonic generation
      imaging (SHGI) and explore various methods for optimization of the technique.
      Second-harmonic imaging is optimized for ultrashort laser pulses, high numerical
      aperture microscope objectives, a highly sensitive non-descanned large area
      detector, pseudo-phase-matching, and specimens with large second-order non
      linearity or which exhibit surface plasmon enhanced phenomena. We also compare
      and contrast the techniques of SHGI and two-photon excited fluorescence imaging.

PMID- 11334740
TI  - Measurement of thin coatings in the confocal microscope.
AB  - The use of the confocal microscope for measurement of the thickness of thin
      transparent coatings, such as the varnish layer on compact discs, is described.
      The relationship between true and apparent thickness varies in a non-linear
      fashion, but intensity profiles show a good correspondence with calculated
      profiles. This provides the basis of a nomogram for prediction of coating
      thickness.

PMID- 11334742
TI  - Differential activation of NF-kappa B subunits in dendritic cells in response to
      Gram-negative bacteria and to lipopolysaccharide.
AB  - Dendritic cell (DC) maturation is essential for the initiation of T-dependent
      immune responses. Nuclear factor kappa B/Rel (NF kappa B/Rel) transcription
      factors are ubiquitously expressed signalling molecules, known to regulate the
      transcription of a large number of genes involved in immune responses, including
      cytokines such as IL-1, IL-6, TNF-alpha and cell surface molecules (MHC class I
      and II, B7.2). In this study, we have compared the activation of five members of
      the NF-kappa B family, p65, c-Rel, p50, RelB and p52, during DC maturation in
      response to lipopolysaccharide (LPS) and to Salmonella typhimurium. We have shown
      that although the translocation of NF-kappa B occurred very early, 30 min after
      treatment with both S. typhimurium and LPS, bacteria-induced NF-kappa B
      activation was more pronounced. Four out of five members, i.e. p65, c-Rel, p50
      and RelB, were similarly activated upon the two stimuli but with different
      kinetics. Indeed, we have observed that p65, c-Rel and p50 were translocated
      early, whereas RelB was translocated later in DC activation. This differential
      regulation suggests that the various members of NF-kappa B family can mediate
      distinct functions of DC physiology.

PMID- 11334743
TI  - Immunomodulation by exogenous surfactant: effect on TNF-alpha secretion and
      luminol-enhanced chemiluminescence activity by murine macrophages stimulated with
      group B streptococci.
AB  - Group B streptococci (GBS) are important pathogens in neonatal sepsis and
      pneumonia. GBS stimulate alveolar macrophages to produce inflammatory cytokines
      and free oxygen radicals, which can damage the lungs. In several studies, use of
      exogenous surfactant in term babies has improved outcome related to sepsis and
      respiratory failure. The role(s) of exogenous surfactant in modulating the
      inflammatory response produced by this microbe was examined. Tumor necrosis
      factor alpha (TNF-alpha) production and luminol-enhanced chemiluminescence (LCL),
      a measure of respiratory burst, were investigated. For measuring TNF-alpha
      release, RAW 264.7 murine macrophages were pre-incubated with bovine surfactant
      and stimulated with either lipopolysaccharide, live or heat-killed GBS type Ia.
      LCL was measured after macrophages were pre-incubated with or without surfactant
      overnight, then stimulated with GBS or phorbol myristate acetate.
      Lipopolysaccharide and GBS stimulated TNF-alpha secretion from macrophages that
      was suppressed by exogenous surfactant in a dose-dependent fashion. GBS and
      phorbol myristate acetate also increased LCL from macrophages, which was
      significantly suppressed by pre-incubation of macrophages with exogenous
      surfactant. We conclude that GBS type Ia stimulates TNF-alpha release and LCL
      from RAW 264.7 cells and that these responses are suppressed by surfactant.
      Suppression of inflammatory mediators by exogenous surfactant might improve
      respiratory disease associated with GBS.

PMID- 11334744
TI  - Introduction to Current focus on Hendra and Nipah viruses.

PMID- 11334745
TI  - Molecular biology of Hendra and Nipah viruses.
AB  - The structure and genetic organization of Hendra and Nipah viruses places them in
      the subfamily Paramyxovirinae. However, low homology with other subfamily members
      and several novel biological and molecular features such as genome length and F(0
      )cleavage site suggest classification in a new genus within the Paramyxovirinae.

PMID- 11334746
TI  - Laboratory diagnosis of Nipah and Hendra virus infections.
AB  - Although Hendra and Nipah viruses emerged to cause novel zoonotic infections only
      recently, there now exists a strong but poorly documented diagnostic capability
      for both. This review gives an overview of the development of the tests, the
      tests currently recommended, their shortcomings and the perceived priorities for
      needed test improvements.

PMID- 11334747
TI  - Ultrastructure of Hendra virus and Nipah virus within cultured cells and host
      animals.
AB  - The ultrastructure of Hendra and Nipah viruses is described in cultured cells,
      pigs, horses and humans. Differences in ultrastructure between the viruses are
      evident within infected cell cultures and lungs from infected amplifier hosts.
      These differences are important in viral identification and differentiation and
      understanding the pathogenesis of disease.

PMID- 11334749
TI  - Comparative pathology of the diseases caused by Hendra and Nipah viruses.
AB  - Information on the pathogenesis and transmissibility of Hendra and Nipah viruses
      was obtained by comparing their histopathology. Both viruses induced syncytial
      cells in vascular tissues and they were primarily vasotropic and/or neurotropic,
      generating interstitial pneumonia or encephalitis. Nipah virus in pigs was also
      epitheliotropic in respiratory epithelium and thus contagious.

PMID- 11334748
TI  - The natural history of Hendra and Nipah viruses.
AB  - Pteropid bats (flying foxes), species of which are the probable natural host of
      both Hendra and Nipah viruses, occur in overlapping populations from India to
      Australia. Ecological changes associated with land use and with animal husbandry
      practices appear most likely to be associated with the emergence of these two
      agents.

PMID- 11334750
TI  - Is antigen presentation the primary function of HLA-G?
AB  - Human histocompatibility leukocyte antigen (HLA)-G is an antigen-presenting
      molecule. This review discusses the possibility that this might not be its
      primary function. HLA-G indeed modulates innate immunity by interacting with
      immunoglobulin-like receptors and by regulating HLA-E expression and its
      subsequent interaction with CD94/NKG2 receptors. HLA-G also down-modulates both
      CD8(+) and CD4(+) T-cell responsiveness.

PMID- 11334751
TI  - Molecular pathogenesis of Citrobacter rodentium and transmissible murine colonic
      hyperplasia.
AB  - Here we review the history, clinical significance, pathology and molecular
      pathogenesis of Citrobacter rodentium, the causative agent of transmissible
      murine colonic hyperplasia. C. rodentium serves as an important model pathogen
      for investigating the mechanisms controlling attaching and effacing pathology,
      epithelial hyperproliferation, and tumor promotion in the distal colon of the
      mouse.

PMID- 11334752
TI  - Xenografts: are the risks so great that we should not proceed?
AB  - Animal organs could save patients needing transplants, but further research is
      necessary to resolve remaining problems with organ rejection. Furthermore,
      xenotransplantation risks transmitting animal pathogens to patients and to the
      general population. It would be unethical to proceed with clinical trials before
      principles and procedures for dealing with this risk are in place.

PMID- 11334753
TI  - Development of a lightweight and adaptable multiple-axis hand prosthesis.
AB  - The last few decades have produced significant improvements in the design of
      upper limb prostheses through the increasing use of technology. However the
      limited function exhibited by these devices remains rooted in their single degree
      of freedom format. Commercial myoelectric hand prostheses warrant high grip
      forces to ensure stable prehension due to a planar pincer movement. Hence precise
      and conscious effort is required on the part of the user to ensure optimum grip.
      Consumers have shown dissatisfaction with the status quo due to the excessive
      weight and poor function of existing artificial hands. Increasing the number of
      grasping patterns and improving the visual feedback from an object in the hand
      are cited as key objectives. This paper outlines the development of the six-axis
      Southampton-Remedi hand prosthesis that addresses these design issues by
      maintaining stable prehension with minimal grip force. Constraints such as
      modularity, anthropomorphism, and low weight and power consumption are factors
      that have been adhered to throughout the design process.

PMID- 11334754
TI  - The effects of drilling force on cortical temperatures and their duration: an in
      vitro study.
AB  - Bone loss due to thermonecrosis may weaken the purchase of surgically placed
      screws and pins, causing them to loosen post-operatively. The goal of this study
      was to determine how differences in applied drilling forces affect the
      temperature of cortical tissue near the drilling site. Results from thermocouples
      placed into fresh cortical bone indicate that increasing the applied drilling
      force resulted in a significant decrease (P=0.001) of maximum cortical
      temperatures. Furthermore, increasing the drilling force resulted in a
      significant decrease (P=0.001) in the average duration of temperature elevations
      above 50 degrees C. The results of the current study demonstrate that by the
      application of a larger force to the drill, both maximum cortical temperatures
      and their duration above 50 degrees C may be effectively reduced, decreasing the
      potential for thermal necrosis in the neighboring cortical bone.

PMID- 11334755
TI  - Parametric studies on the phase shift method to measure the blood perfusion of
      biological bodies.
AB  - To better understand the phase shift method to non-invasively measure the blood
      perfusion of living tissues in vivo, the dual reciprocity boundary element method
      (DRBEM) was applied to numerically solve the transient and non-linear two
      dimensional bio-heat transfer in biological bodies subject to a sinusoidal heat
      flux at the skin surface. The influences of the heating flux, the heating
      oscillation magnitude, the heating frequency, the blood vessel underneath the
      skin, and the space or temperature dependent blood perfusion to the temperature
      response and the phase shift between the heat flux and the temperature response
      at the skin surface were comprehensively examined. The effects of the heating
      area to the temperature response were also investigated. And a better
      understanding on the heat transfer behavior of biological bodies under sinusoidal
      heating was thus obtained. These results are expected to be valuable for
      constructing the practical instrumentation to non-invasively measure the blood
      perfusion of biological bodies.

PMID- 11334756
TI  - Principal component analysis of the power developed in the flexion/extension
      muscles of the hip in able-bodied gait.
AB  - This study was undertaken to demonstrate how principal component analysis (PCA)
      can be used: (a) to detect the main functional structure of actions taken by hip
      extensors and flexors during two consecutive gait cycles of able-bodied subjects,
      and (b) to determine whether or not symmetrical behaviour exists between right
      and left hip muscle power activity. Twenty young, healthy male subjects walked
      along a 13 m path at a freely-chosen speed. Applying curve structure detection
      methods such as PCA to walking patterns can provide insight into the functional
      tasks accomplished by the lower limbs of able-bodied and disabled subjects. PCA
      was applied as a classification and curve structure detection method to hip
      sagittal muscle power calculated for the right and left lower limbs. Over 70% of
      the information provided by the first four principal components (PCs) was chosen
      for further biomechanical interpretation. PC1 for both right and left sides
      mainly described the action taken by the hip extensors/flexors corresponding to
      the vertical component of ground force on the respective limbs during mid-stance.
      Propulsion and limb preparation were identified as the second and third tasks
      attributed to right hip muscle power, while between limb co-ordination was
      recognised as the second and third functional tasks of the left hip
      extensors/flexors. Balance was identified as the fourth main functional
      contribution of the hip extensors/flexors at the right limb while for the left
      limb, these muscles were mainly responsible for preparing the limb to enter into
      new gait cycle. PCA was able to identify the four main functional contributions
      of hip sagittal muscle power during able-bodied gait. PCA was also able to
      examine the existence of functional asymmetry in gait by highlighting different
      task priorities at the hip level for the right and left lower limbs.

PMID- 11334757
TI  - A model of an electro-goniometer and its calibration for biomechanical
      applications.
AB  - The paper describes a detailed model of an electro-goniometer based on a elastic
      beam connecting two 'bases' whose relative orientation should be measured. This
      kind of device, which has been developed for the analysis of human motion, is
      also suitable for different applications even when one or more rotations around
      moving axes occur. After a theoretical analysis of the device working principles,
      experimental verifications of the model are presented. The paper analyses the
      characteristics of the device and shows how the goniometer outputs can be
      converted into more familiar angular conventions avoiding cross-talk and other
      artifacts.

PMID- 11334758
TI  - A new ankle laxity tester and its use in the measurement of the effectiveness of
      taping.
AB  - Damage to the lateral ligaments of the ankle, namely the anterior talofibular
      (ATFL) and the calcaneofibular (CFL) ligaments, is a frequently reported sports
      injury. The anterior drawer test is generally used to evaluate whether the ATFL
      has been torn, while the talar tilt test is used to determine if the CFL has been
      injured. Although these two manual tests are often utilized for quick diagnosis,
      they have been criticized because of their subjective nature and their inability
      to produce quantitative and reproducible results. A prototype ankle tester was
      manufactured that could measure the input force and torque, as well as the linear
      and angular deprivations for the anterior drawer test and the talar tilt test,
      respectively. This device was used to take readings on 10 human volunteers of a
      mean age of 21.6 years. This device was X-ray compatible, adjustable for varying
      patient sizes, relatively small, portable, and easy to operate. Testing was
      performed to determine how the stiffness of the ankle would respond to taping,
      and the effect of walking on the taped ankle. The overall mean anterior drawer
      was 5.93 mm and the mean talar tilt was 51.6 degrees for bare ankles using a
      force of 111 N (25 lbs) for the drawer and a torque of 16 N m for the tilt.
      Taping provided an average increase in stiffness of 11.3%, demonstrating that it
      did provide increased stability. However, statistically significant (P<0.05)
      decreases in the stiffness subsequent to taping were observed between the
      initially taped ankles and after 20 min of walking, when it was shown that talar
      tilt had increased. The prototype ankle tester produced repeatable measurements,
      and results show that the increase in stiffness due to taping did decrease after
      a short period of time.

PMID- 11334759
TI  - Stability of Fourier coefficients in relation to changes in respiratory air flow
      patterns.
AB  - The characterization of respiratory air flow patterns is a subject of continuous
      interest. The pattern of the air flow curve is an individual characteristic which
      remains constant over long periods of time. Basically two different approaches
      have been proposed to determine the individual parameters of the respiratory
      flow, namely the graphical characterization, which originated from visual indices
      and subsequently led to harmonic analysis, and the optimal control modeling
      approach. It has been suggested that respiratory personality can be accurately
      characterized by the Fourier coefficients of the air flow curve. The first four
      Fourier sine components should reproduce the shape of the cycle and remain
      constant in different environmental conditions for one individual. This paper
      evaluates the possibilities of the Fourier approximation approach to characterize
      the respiratory personality. The Fourier sine coefficients which were assumed to
      be invariable were found to be very sensitive to changes in respiratory times.
      Both the amplitude and the angle of the Fourier sine transformation varied when
      duration of inspiration and expiration changed.

PMID- 11334760
TI  - Measurement of thermal conductivity of bovine cortical bone.
AB  - The thermal conductivity of cortical bone was characterized experimentally.
      Specimens were taken from the mid-diaphysis of bovine femora, and the rate of
      heat transfer was measured in three orthogonal directions. The conductivity was
      found to be 0.58+/-0.018 W/mK in the longitudinal direction, 0.53+/-0.030 W/mK in
      the circumferential direction, and 0.54+/-0.020 W/mK in the radial direction.
      Because the directional differences are small, it is concluded that bovine
      cortical bone can be treated as thermally isotropic.

PMID- 11334761
TI  - Pressure, platelets, and plaque: the central role of angiotensin II in
      cardiovascular pathology. Introduction.

PMID- 11334762
TI  - Experimental and clinical evidence that angiotensin II is an independent risk
      factor for cardiovascular disease.
AB  - The role of the renin-angiotensin system in the regulation of normal blood
      pressure and in the pathogenesis of hypertension has long been appreciated.
      Angiotensin II (Ang II) was originally thought to only influence blood pressure,
      but the results of many preclinical and clinical studies now suggest that Ang II
      has an important and distinct role in other cardiovascular pathologies. Drugs
      that interfere with the renin-angiotensin system, such as angiotensin-converting
      enzyme (ACE) inhibitors, are now widely accepted for the treatment of chronic
      renal failure and heart failure. Recent studies have shown that Ang II acts
      directly on the myocardium to cause ventricular hypertrophy, a response that can
      be prevented or reversed by selective Ang II type 1 receptor antagonists. The
      utility of angiotensin receptor antagonists in the treatment of chronic renal
      failure has been demonstrated, and the results of ongoing clinical trials can be
      expected to prove their benefit in other cardiovascular pathologies.

PMID- 11334763
TI  - Angiotensin II and the pathophysiology of cardiovascular remodeling.
AB  - Hypertension is associated with a number of adverse morphologic and functional
      changes in the cardiovascular system. These include remodeling of the left
      ventricle, alterations in the morphology and mechanical properties of the
      vasculature, and the development of endothelial dysfunction. Recent studies have
      shown that angiotensin II is capable of mediating these changes via its
      interaction with the angiotensin II type 1 receptor. These nonhemodynamic effects
      of angiotensin II are independent of its effect on blood pressure. Thus, elevated
      levels of angiotensin II may lead directly to many hypertension-associated
      pathologies. Recent evidence that mechanical strain, oxidized low-density
      lipoprotein cholesterol, and aldosterone can cause upregulation of angiotensin II
      type 1 receptors indicates that activation of the renin-angiotensin system is not
      necessary for the actions of angiotensin II to be amplified. Because the strain
      on the vessel wall may be increased under conditions of hypertension, increased
      arterial pressure may amplify the actions of angiotensin II without a discernible
      increase in plasma angiotensin II levels. In both the myocardium and the
      peripheral vasculature, fibrosis is a major component of the remodeling that
      occurs in hypertension. There is substantial evidence that transforming growth
      factor beta-1 (TGF-beta(1)) mediates angiotensin-II-induced fibrosis in patients
      with hypertension and in those with a variety of nephropathies. Mechanical strain
      also induces fibrosis in a mechanism mediated by TGF-beta(1). This cytokine thus
      represents a common pathway by which angiotensin II and increased arterial
      pressure may induce cardiovascular fibrosis.

PMID- 11334764
TI  - Angiotensin, fibrinolysis, and vascular homeostasis.
AB  - There is strong evidence that imbalance of the fibrinolytic system is involved in
      the pathogenesis of ischemic cardiovascular events. A reduction in fibrinolytic
      function may also mediate part of the adverse response of the vasculature to
      conditions of low nitric oxide production. Because reduced nitric oxide activity
      predisposes to the development of atherosclerosis, imbalance of the fibrinolytic
      system is heavily implicated in the development of cardiovascular pathology. The
      renin-angiotensin system exerts substantial control over the fibrinolytic system,
      and pharmacologic interventions that reduce the activity of angiotensin II also
      have favorable effects on fibrinolytic balance and on the incidence of adverse
      cardiovascular events. This review summarizes the evidence for a link between
      activation of the renin-angiotensin system, fibrinolytic imbalance, and
      cardiovascular pathology.

PMID- 11334765
TI  - Angiotensin II and atherosclerosis.
AB  - Numerous clinical and laboratory data are now available supporting the hypothesis
      that the renin-angiotensin system is mechanistically relevant in the pathogenesis
      of atherosclerosis. The traditional role of the renin-angiotensin system in the
      context of blood pressure regulation has been modified to incorporate the concept
      that angiotensin II (Ang II) is a potent proinflammatory agent. In vascular
      cells, Ang II is a potent stimulus for the generation of reactive oxygen species.
      As a result, Ang II upregulates the expression of many redox-sensitive cytokines,
      chemokines, and growth factors that have been implicated in the pathogenesis of
      atherosclerosis. Extensive data now confirm that inhibition of the renin
      angiotensin system inhibits atherosclerosis in animal models as well as in
      humans. These studies provide mechanistic insights into the precise role of Ang
      II in atherosclerosis and suggest that pharmacologic interventions involving the
      renin-angiotensin system may be of fundamental importance in the treatment and
      prevention of atherosclerosis.

PMID- 11334766
TI  - New pharmacologic aspects of CS-866, the newest angiotensin II receptor
      antagonist.
AB  - CS-866 is a new angiotensin II receptor blocker that has demonstrated
      effectiveness for lowering blood pressure in animal models of hypertension. Given
      the proposed involvement of the renin-angiotensin system in diabetic nephropathy
      and atherosclerosis, we have tested CS-866 in animal models of these conditions.
      The renal protective properties of CS-866 were examined in the Zucker diabetic
      fatty (ZDF) rat, a model of type 2 diabetes that develops progressive
      hyperglycemia, glomerulosclerosis, and proteinuria. Treatment of ZDF rats with CS
      866 in the diet for 19 weeks resulted in a dose-dependent reduction in urinary
      protein excretion compared with vehicle-treated control rats, which was
      independent of changes in blood pressure and glycemic state. The
      antiatherosclerotic properties of CS-866 were tested in 2 animal models. In the
      first study, cynomolgus monkeys were fed a high-cholesterol diet for 6 months
      while receiving CS-866 or vehicle. At the end of this period, CS-866-treated
      animals had 64% less plaque area in the aorta than controls. CS-866 was also
      tested in the Watanabe heritable hyperlipidemic (WHHL) rabbit model of
      atherosclerosis. WHHL rabbits were treated for 32 weeks with CS-866 (1 mg/kg),
      pravastatin (50 mg/kg), a combination of the 2 drugs, or vehicle. CS-866 had no
      effect on plasma cholesterol levels and reduced blood pressures minimally.
      Pravastatin alone reduced serum cholesterol but had no effect on blood pressure
      or lesion area. In contrast, treatment with CS-866 resulted in a 40% reduction in
      lesion area compared with vehicle-treated control when given alone and a 50%
      reduction in combination with pravastatin. On the basis of results from animal
      models, CS-866 may be a useful treatment for diabetic nephropathy and
      atherosclerosis.

PMID- 11334767
TI  - Clinical studies of CS-866, the newest angiotensin II receptor antagonist.
AB  - Angiotensin II receptor blockers have shown widespread efficacy as
      antihypertensive medications. These agents bind selectively to angiotensin II
      type 1 (AT(1)) receptors, specifically blocking the renin-angiotensin system at
      the last step in its cascade. CS-866 is the most recently introduced drug in this
      class. This article presents integrated safety and efficacy data from 7
      randomized, double-blind, placebo-controlled, parallel group studies in which
      once-daily CS-866 monotherapy was used in the treatment of patients with
      essential hypertension (sitting diastolic blood pressure > or =100 mm Hg and < or
      =115 mm Hg). Data from a total of 2,145 CS-866-treated patients were included in
      the efficacy analysis. Safety data were available from 2,540 CS-866-treated
      patients, with a cumulative exposure of 5,888 patient-months. The
      antihypertensive efficacy of the drug was assessed using both cuff blood pressure
      measurements and 24-hour ambulatory blood pressure monitoring. The data show that
      CS-866 is effective and safe for the treatment of hypertension. Dose-dependent
      reductions in both diastolic and systolic blood pressures occurred within 1 week
      of initiating treatment, and the response was almost maximal within 2 weeks.
      There was no difference in efficacy between younger (<65 years) and older (> or
      =65 years) groups of patients. Trough-to-peak ratios showed that CS-866 retains
      the majority of its peak effect 24 hours after treatment, and is therefore
      suitable for once-daily dosing. Dizziness was the only treatment-emergent adverse
      event with which CS-866 was associated.

PMID- 11334768
TI  - Pressure, platelets, and plaque: the central role of angiotensin II in
      cardiovascular pathology. Concluding comment.

PMID- 11334769
TI  - Introduction and overview: beta-blocker therapy in the management of chronic
      heart failure.

PMID- 11334770
TI  - New epidemiologic perspectives concerning mild-to-moderate heart failure.
AB  - Heart failure is emerging as a major component of the public health problem of
      cardiovascular disease as we move into the twenty-first century. Current
      statistics indicate 4.9 million US citizens are afflicted with direct treatment
      costs estimated to be $18.8 billion per year. These figures are expected to
      worsen substantially as the prevalence of heart failure continues to increase.
      Epidemiologic studies also point to important increases in morbidity and have
      identified risk factors that aid in prognosis and that may contribute to our
      mechanistic understanding of heart failure pathophysiology. In addition,
      epidemiologic results indicate that many patients with mild-to-moderate clinical
      heart failure are still at substantial risk for morbidity and mortality during
      follow-up periods of only a few years. These data highlight the importance of
      enhancing physician and public awareness of heart failure. New methods of
      molecular epidemiology will point toward better and earlier detection of this
      common and frequently fatal condition.

PMID- 11334772
TI  - Prognosis determination in heart failure.

PMID- 11334774
TI  - Pathophysiology of chronic heart failure.
AB  - Heart failure is a changing paradigm. The hemodynamic model, which served our
      needs well from the 1950s through the early 1980s, has now been largely
      abandoned, except for the management of decompensated patients in the hospital.
      The pathophysiology is exceedingly complex and involves structural changes, such
      as loss of myofilaments, apoptosis and disorganization of the cytoskeleton, as
      well as disturbances in Ca(2+) homeostasis, alteration in receptor density,
      signal transduction, and collagen synthesis. A more contemporary working
      hypothesis is that heart failure is a progressive disorder of left ventricular
      remodeling, usually resulting from an index event, that culminates in a clinical
      syndrome characterized by impaired cardiac function and circulatory congestion.
      This change in the framework of our understanding of the pathophysiology of heart
      failure is predicated on the results of numerous clinical trials conducted during
      the past 20 years. New therapies are now evolving that are designed to inhibit
      neuroendocrine and cytokine activation, whereas drugs specifically designed to
      heighten cardiac contractility and "unload" the left ventricle have proven to be
      unhelpful in long-term management of patients with chronic heart failure.
      However, the hemodynamic model is still relevant for patients in the hospital
      with decompensated heart failure, where positive inotropic drugs and vasodilators
      are still widely used. The modern treatment of chronic heart failure is now
      largely based on the neurohormonal hypothesis, which states that neuroendocrine
      activation is important in the progression of heart failure and that inhibition
      of neurohormones is likely to have long-term benefit with regard to morbidity and
      mortality. Thus, the evolution of treatment for chronic heart failure as a result
      of clinical trials has provided much enlightenment for our understanding of the
      fundamental biology of the disorder, a reversal of the usual flow of information
      from basic science to clinical investigation.

PMID- 11334776
TI  - Medical management of mild-to-moderate heart failure before the advent of beta
      blockers.
AB  - Clinical trials of beta blockers in heart failure have generally required that
      patients be receiving optimal drug therapy before randomization to the study
      medication. Therefore, because beta blockers are used in addition to conventional
      drug therapy, review of the standard drug therapy of mild-to-moderate heart
      failure before the advent of beta blockade is essential to understanding the role
      of beta blockers in the treatment of heart failure. The conventional medical
      management of systolic heart failure includes angiotensin-converting enzyme (ACE)
      inhibitors, which should be used as first-line therapy; diuretics, for the
      management of body fluid-volume excess; digoxin; and some other vasodilators.
      These therapies have been evaluated in large-scale, randomized, controlled
      trials. ACE inhibitors have been shown to significantly attenuate disease
      progression and improve outcome (ie, morbidity and mortality) in patients with
      mild-to-moderate systolic heart failure. Controversial or unproven therapies
      include nonglycoside inotropic agents, angiotensin II receptor antagonists,
      antiarrhythmic agents, anticoagulants, and calcium channel blockers. The
      pharmacologic management of diastolic heart failure is largely empirical and is
      directed at reducing symptoms. Symptoms caused by increased ventricular filling
      pressures may be treated with diuretics and long-acting nitrates. Some calcium
      channel blockers and most beta blockers prolong diastolic filling time by slowing
      heart rate, thereby potentially improving the symptoms of diastolic heart
      failure. Calcium antagonists, beta blockers, diuretics, and ACE inhibitors may
      also promote regression of left ventricular hypertrophy and thus improve
      ventricular compliance, possibly preventing the development of diastolic
      dysfunction. Because randomized controlled trials of diastolic heart failure are
      lacking, this review focuses on the conventional management of mild-to-moderate
      systolic heart failure before the advent of beta blockade.

PMID- 11334778
TI  - Risks and benefits of a multidrug approach to mild-to-moderate heart failure.
AB  - Multidrug therapy offers several advantages in the management of mild-to-moderate
      heart failure. Treatment with a combination of agents, such as diuretics,
      digoxin, angiotensin-converting enzyme inhibitors, and beta blockers, can provide
      relief of symptoms while also addressing specific pathophysiologic factors. By
      allowing therapy to be tailored to the individual, the multidrug approach can
      slow progression of the disease, reduce or prevent the need for hospitalization,
      and decrease health-care costs. Evidence of the benefit of the multidrug approach
      has come from numerous trials in which newer treatments for heart failure have
      been evaluated in the context of the background therapy considered standard at
      the time of the trial. Compliance may be a challenge with multidrug therapy,
      particularly for patients who generally feel well and do not experience symptoms
      that interfere with normal daily function. The clinician must ensure that
      patients understand the need to comply with the prescribed regimen to prevent
      more serious problems in the future. Multidrug therapy may also require that
      patients be more closely monitored so that dosages of the individual medications
      can be adjusted to provide maximum benefit with a minimum of side effects.

PMID- 11334780
TI  - Practical aspects of using beta-adrenergic blockade in systolic heart failure.
AB  - Heart failure exacts a severe human and public health toll. In the United States,
      heart failure afflicts approximately 5 million patients and is responsible for or
      contributes to 3 million hospitalizations and 300,000 deaths yearly. Physicians
      can have a major impact on this disease by using effective agents for the
      treatment of heart failure (particularly angiotensin-converting enzyme [ACE]
      inhibitors and beta blockers), yet the actual clinical use of these drugs
      (especially the use of beta blockers by primary physicians) is disappointingly
      low. Many physicians appear to be reluctant to prescribe beta blockers for two
      reasons. First, they are concerned about the potential interference of beta
      blockers with important compensatory mechanisms that support the failing heart
      and fear that such interference may lead to clinical deterioration. Second, they
      fail to identify patients with heart failure (especially those with mild or
      moderate symptoms) or regard such patients as being too well to require
      additional treatment. These reasons should no longer be used as excuses to avoid
      the use of these drugs, given the persuasive evidence that beta blockers can
      improve symptoms and prolong life in patients with heart failure. Instead,
      physicians must recognize that long-term activation of the sympathetic nervous
      system primarily exerts deleterious (rather than compensatory) effects in
      patients with heart failure and that these actions can be antagonized effectively
      and safely by the appropriate use of beta-blocking drugs.

PMID- 11334781
TI  - Economic impact of beta blockade in heart failure.
AB  - We reviewed the literature on clinical trials of beta-adrenergic blockade for
      treatment of heart failure, seeking evidence of reductions in hospital
      admissions. To analyze the economic implications of six clinical trials, we
      developed a stochastic cost model to generate estimates of total medical costs
      resulting from heart failure and related causes. The model includes inpatient,
      outpatient, and professional cost estimates based on Medicare claims data, and it
      is driven by traditional endpoint statistics reported in the clinical trial
      literature. It provides a common framework for comparing cost effectiveness
      across clinical trials in the absence of detailed cost information collected in
      the trial. The incremental expected cost per year of life saved is $3,300 for
      bisoprolol, $2,500 for metoprolol, and $6,700 for carvedilol. The cost per year
      of life saved for each compound is well below accepted standards for cost
      effectiveness. These results are sensitive to the cost of drug therapy and the
      relative mortality rate for the experimental group. For example, if the relative
      mortality rate of the experimental group were to increase from the reported 40%
      to 82%, and if the annual cost of the drug were to decrease from $2,000 to $500,
      then we estimate that carvedilol would break even and the cost per year of life
      saved would drop to zero. Whether beta-blocker therapy, as assumed, sustains its
      differential effectiveness in terms of relative mortality risk beyond the study
      duration has not been demonstrated.

PMID- 11334782
TI  - Current role of beta-adrenergic blockers in the management of chronic heart
      failure.
AB  - Long-term activation of the sympathetic nervous system exerts adverse biologic
      effects that are mediated through alpha(1), beta(1) and beta(2) receptors and
      that contribute importantly to the progression of heart failure. As a result,
      beta blockers are no longer considered to be contraindicated for use in these
      patients but instead now play a critical role in the successful management of
      chronic heart failure. Beta blockers have been evaluated in >15,000 patients with
      heart failure who have participated in placebo-controlled trials. The results of
      these studies indicate that, like angiotensin-converting enzyme (ACE) inhibitors,
      long-term treatment with beta blockers can lessen symptoms and improve clinical
      status and can reduce the risk of death as well as the combined risk of death or
      hospitalization. The database supporting the use of beta blockers is now as
      persuasive (and arguably more persuasive) than the database supporting the use of
      ACE inhibitors in heart failure (which comprises about 7,000 patients). Yet, the
      benefits of beta blockers are seen in patients already receiving ACE inhibitors,
      suggesting that combined blockade of two neurohormonal systems (renin-angiotensin
      system and sympathetic nervous system) can produce additive effects.

PMID- 11334783
TI  - Proton transfer in Azotobacter vinelandii ferredoxin I: entatic Lys84 operates as
      elastic counterbalance for the proton-carrying Asp15.
AB  - In ferredoxin I from Azotobacter vinelandii, the reduction of a [3Fe-4S] iron
      sulphur cluster is coupled with the protonation of the mu2S sulphur atom that is
      approx. 6 A away from the protein boundary. The recent study of the site-specific
      mutants of ferredoxin I led to the conclusion that a particular surface aspartic
      residue (Asp15) is solely responsible for the proton transfer to the mu2S atom by
      'rapid penetrative excursions' (K. Chen, J. Hirst, R. Camba, C.A. Bonagura, C.D.
      Stout, B.K. Burgess, F.A. Armstrong, Nature 405 (2000) 814-817). In the same
      paper it has been reported that the replacement of Asp15 by glutamate led to the
      blockage of the enzyme, although glutamate, with its longer and more flexible
      side chain, should apparently do even better as a mobile proton carrier than
      aspartate. We tackled this puzzling incompetence of Glu15 by molecular dynamics
      simulations. It was revealed that the conformational alterations of Asp15 are
      energetically balanced by the straining of the nearby Lys84 side chain in wild
      type ferredoxin I but not in the Asp15-->Glu mutant. Lys84 in ferredoxin I of A.
      vinelandii seems to represent the first case where the strained (entatic)
      conformation of a particular amino acid side chain could be directly identified
      in the ground state of an enzyme and assigned to a distinct mechanism of energy
      balance during the catalytic transition.

PMID- 11334784
TI  - A novel scenario for the evolution of haem-copper oxygen reductases.
AB  - The increasing sequence information on oxygen reductases of the haem-copper
      superfamily, together with the available three-dimensional structures, allows a
      clear identification of their common, functionally important features. Taking
      into consideration both the overall amino acid sequences of the core subunits and
      key residues involved in proton transfer, a novel hypothesis for the molecular
      evolution of these enzymes is proposed. Three main families of oxygen reductases
      are identified on the basis of common features of the core subunits, constituting
      three lines of evolution: (i) type A (mitochondrial-like oxidases), (ii) type B
      (ba3-like oxidases) and (iii) type C (cbb3-type oxidases). The first group can be
      further divided into two subfamilies, according to the helix VI residues at the
      hydrophobic end of one of the proton pathways (the so-called D-channel): (i) type
      A1, comprising the enzymes with a glutamate residue in the motif -XGHPEV-, and
      (ii) type A2, enzymes having instead a tyrosine and a serine in the alternative
      motif -YSHPXV-. This second subfamily of oxidases is shown to be ancestor to the
      one containing the glutamate residue, which in the Bacteria domain is only
      present in oxidases from Gram-positive or purple bacteria. It is further proposed
      that the Archaea domain acquired terminal oxidases by gene transfer from the Gram
      positive bacteria, implying that these enzymes were not present in the last
      common ancestor before the divergence between Archaea and Bacteria. In fact, most
      oxidases from archaea have a higher amino acid sequence identity and similarity
      with those from bacteria, mainly from the Gram-positive group, than with oxidases
      from other archaea. Finally, a possible relation between the dihaemic subunit
      (FixP) of the cbb3 oxidases and subunit II of caa3 oxidases is discussed. As the
      families of haem-copper oxidases can also be identified by their subunit II, a
      parallel evolution of subunits I and II is suggested.

PMID- 11334785
TI  - Heterologous expression and properties of the gamma-subunit of the Fe-only
      hydrogenase from Thermotoga maritima.
AB  - Thermotoga maritima is a hyperthermophilic bacterium that contains a complex,
      heterotrimeric (alpha(beta)gamma) Fe-only hydrogenase. Sequence analysis
      indicates that the gene encoding the smallest subunit (gamma), hydC, contains a
      predicted iron-sulfur cluster binding motif. However, characterization of the
      native gamma-subunit has been hampered by interference from and the inability to
      separate intact gamma-subunit from the other two subunits (alpha and beta). To
      investigate the function and properties of the isolated gamma-subunit, the gene
      encoding HydG was expressed in Escherichia coli. Two forms of the recombinant
      protein were obtained with molecular masses of 10 and 18 kDa, respectively. Both
      contained a single [2Fe-2S] cluster based on metal analysis, EPR and UV-visible
      spectroscopy. NH2-terminal sequencing revealed that the 10 kDa protein is a
      truncated form of the intact gamma-subunit and lacks the first 65 amino acid
      residues. The midpoint potential of the 18 kDa form was -356 mV at pH 7.0 and 25
      degrees C, as measured by direct electrochemistry, and was pH dependent with a
      pK(ox) of 7.5 and a pK(red) of 7.7. The oxidized, recombinant gamma-subunit was
      stable at 80 degrees C under anaerobic conditions with a half-life greater than
      24 h, as judged by the UV-visible spectrum of the [2Fe-2S] cluster. In the
      presence of air the protein was less stable and denatured with a half-life of
      approx. 2.5 h. The recombinant gamma-subunit was electron transfer competent and
      was efficiently reduced by pyruvate ferredoxin oxidoreductase from Pyrococcus
      furiosus, with a Km of 5microM and a Vmax of 9 U/mg. In contrast, native T.
      maritima hydrogenase holoenzyme and its separated alpha-subunit were much less
      effective electron donors for the gamma-subunit, with a V(max) of 0.01 U/mg and
      0.1 U/mg, respectively.

PMID- 11334786
TI  - What controls the outer mitochondrial membrane permeability for ADP: facts for
      and against the role of oncotic pressure.
AB  - In our study 10% of bovine serum albumin was added to the physiological
      incubation medium to mimic the oncotic pressure of the cellular cytoplasm and to
      test for its effect on the respiration of isolated rat heart mitochondria,
      saponin- or saponin plus crude collagenase (type IV)-treated heart muscle fibers
      and saponin-treated rat quadriceps muscle fibers. Pyruvate and malate were used
      as substrates. We found that albumin slightly decreased the maximal ADP
      stimulated respiration rate only for saponin-treated heart muscle fibers. The
      apparent Km ADP of oxidative phosphorylation increased significantly, by 70-100%,
      for isolated heart mitochondria, saponin plus collagenase-treated heart muscle
      fibers and for saponin-treated quadriceps muscle fibers but remained unchanged
      for saponin-treated heart muscle fibers. The saponin-treated heart muscle fibers
      were characterized by a very high control apparent Km ADP value (234+/-24 microM
      ADP) compared with other preparations (14-28 microM ADP). The results suggest
      that in vivo the oncotic pressure is not the relevant factor causing the low
      outer mitochondrial membrane permeability for ADP in cardiomyocytes, in contrast
      to quadriceps muscle cells. It is likely that the outer mitochondrial membrane
      bound protein(s) which is supposed to remain in saponin-treated heart muscle
      fibers is responsible for this property of the membrane.

PMID- 11334787
TI  - Mitochondrial membrane potential in density-separated trout erythrocytes exposed
      to oxidative stress in vitro.
AB  - Previous literature reports have demonstrated that nucleated trout erythrocytes
      in condition of oxidative stress are subjected to DNA and membrane damage, and
      inactivation of glutathione peroxidase. The present study was undertaken to
      investigate if mitochondrial membrane potential in stressed conditions was also
      influenced. Density-separated trout erythrocyte fractions, obtained using a
      discontinuous Percoll gradient, were submitted to stress conditions and the
      mitochondrial membrane potential was determined by means of cytofluorimetric
      analysis after incubation of each subfraction with JC-1, a mitochondrial specific
      fluorescent probe. The results clearly show that the mitochondrial membrane
      potential decreased significantly in all erythrocyte fractions, also if the
      oxidative effect on mitochondria is more severe with increased density (age) of
      the cell. Ebselen was very effective in preventing mitochondrial depolarization
      in young as well as in old erythrocytes.

PMID- 11334788
TI  - Site specific labeling of Rhodobacter sphaeroides reaction centers with dye
      probes for surface pH measurements.
AB  - Covalently bound pH sensitive dyes are an important tool for characterizing the
      proteolytic reactions of protein complexes that play key roles in biological
      energy transduction. Here we demonstrate the feasibility of this method for
      photosynthetic reaction centers (RCs) for the first time, by the highly selective
      attachment of two thiol reactive derivatives of fluorescein to the two H subunit
      cysteines of the photosynthetic RC from Rhodobacter sphaeroides R-26 The pK(a)
      shifts of the dyes upon binding to the protein and in response to high salt were
      measured, and interpreted based on the structure of the RC. 2-[(5
      fluoresceinyl)aminocarbonyl]ethyl-methanethiosulfonate was attached to Cys H156
      and fluorescein-5-maleimide to Cys H234. By following the absorption changes of
      bound fluorescein (500 nm), and those of the hydrophilic pH indicator 8
      hydroxypyrene-1,3,6-tris-sulfonic acid (468 nm), the surface and bulk pH were
      monitored separately with less than 5% crosstalk. Flash-induced proton uptake and
      external calibrations by mixing with aliquots of acid were measured in different
      redox states of the RCs. The results indicate that the charge in the quinone
      acceptor complex after flash activation (primary quinone acceptor (Q(A))- or
      secondary quinone acceptor (Q(B))-) has no effect on the surface pH and potential
      in the vicinity of these two attachment sites, between pH 6.5 and 9. Application
      of the method to other surface locations is discussed.

PMID- 11334789
TI  - Photosystem stoichiometry and state transitions in a mutant of the cyanobacterium
      Synechococcus sp. PCC 7002 lacking phycocyanin.
AB  - Phycobilisomes (PBS) function as light-harvesting antenna complexes in
      cyanobacteria, red algae and cyanelles. They are composed of two substructures:
      the core and peripheral rods. Interposon mutagenesis of the cpcBA genes of
      Synechococcus sp. PCC 7002 resulted in a strain (PR6008) lacking phycocyanin and
      thus the ability to form peripheral rods. Difference absorption spectroscopy of
      whole cells showed that intact PBS cores were assembled in vivo in the cpcBA
      mutant strain PR6008. Fluorescence induction measurements demonstrated that the
      PBS cores are able to deliver absorbed light energy to photosystem (PS) II, and
      fluorescence induction transients in the presence of DCMU showed that PR6008
      cells could perform a state 2 to state 1 transition with similar kinetics to that
      of the wild-type cells. Thus, PBS core assembly, light-harvesting functions and
      energy transfer to PS I were not dependent upon the assembly of the peripheral
      rods. The ratio of PS II:PS I in the PR6008 cells was significantly increased,
      nearly twice that of the wild-type cells, possibly a result of long-term
      adaptation to compensate for the reduced antenna size of PS II. However, the
      ratio of PBS cores:chlorophyll remained unchanged. This result indicates that
      approximately half of the PS II reaction centers in the PR6008 cells had no
      closely associated PBS cores.

PMID- 11334790
TI  - Lack of dystrophin is associated with altered integration of the mitochondria and
      ATPases in slow-twitch muscle cells of MDX mice.
AB  - The potential role of dystrophin-mediated control of systems integrating
      mitochondria with ATPases was assessed in muscle cells. Mitochondrial
      distribution and function in skinned cardiac and skeletal muscle fibers from
      dystrophin-deficient (MDX) and wild-type mice were compared. Laser confocal
      microscopy revealed disorganized mitochondrial arrays in m. gastrocnemius in MDX
      mice, whereas the other muscles appeared normal in this group. Irrespective of
      muscle type, the absence of dystrophin had no effect on the maximal capacity of
      oxidative phosphorylation, nor on coupling between oxidation and phosphorylation.
      However, in the myocardium and m. soleus, the coupling of mitochondrial creatine
      kinase to adenine nucleotide translocase was attenuated as evidenced by the
      decreased effect of creatine on the Km for ADP in the reactions of oxidative
      phosphorylation. In m. soleus, a low Km for ADP compared to the wild-type
      counterpart was found, which implies increased permeability for that nucleotide
      across the mitochondrial outer membrane. In normal cardiac fibers 35% of the ADP
      flux generated by ATPases was not accessible to the external pyruvate kinase
      phosphoenolpyruvate system, which suggests the compartmentalized (direct)
      channeling of that fraction of ADP to mitochondria. Compared to control, the
      direct ADP transfer was increased in MDX ventricles. In conclusion, our data
      indicate that in slow-twitch muscle cells, the absence of dystrophin is
      associated with the rearrangement of the intracellular energy and feedback signal
      transfer systems between mitochondria and ATPases. As the mechanisms mediated by
      creatine kinases become ineffective, the role of diffusion of adenine nucleotides
      increases due to the higher permeability of the mitochondrial outer membrane for
      ADP and enhanced compartmentalization of ADP flux.

PMID- 11334791
TI  - Cold-induced changes in the energy coupling and the UCP3 level in rodent skeletal
      muscles.
AB  - The mechanism of thermoregulatory uncoupling of respiration and phosphorylation
      in skeletal muscles has been studied. It is found that 24 h cold exposure results
      in (i) a 3-fold increase in the amount of UCP3 protein in rat skeletal muscle
      mitochondria, and (ii) pronounced lowering of the membrane potential in isolated
      rat or mouse skeletal muscle mitochondria. The decrease in membrane potential is
      reversed by adding bovine serum albumin. Cold exposure is also found to sensitize
      the membrane potential to the uncoupling action of added fatty acid (laurate).
      After laurate addition, the recoupling effects of GDP and carboxyatractylate
      decrease whereas that of albumin increases in mitochondria from cold-treated rats
      or mice. Changes similar to those induced by cold can be initiated by the in vivo
      addition of thyroxine. Cold exposure does not affect energy coupling in liver
      mitochondria. The possible involvement of UCP3 isoforms in nucleotide-sensitive
      and -insensitive uncoupling is discussed.

PMID- 11334792
TI  - Proton uptake associated with the reduction of the primary quinone Q(A)
      influences the binding site of the secondary quinone Q(B) in Rhodopseudomonas
      viridis photosynthetic reaction centers.
AB  - Previously, two binding sites for the secondary quinone Q(B) in the
      photosynthetic reaction center (RC) from Rhodopseudomonas viridis were identified
      by X-ray crystallography, a 'proximal' binding site close to the non-heme iron,
      and a 'distal' site, displaced by 4.2 A along the path of the isoprenoid tail
      [C.R.D. Lancaster and H. Michel, Structure 5 (1997) 1339-1359]. The quinone ring
      planes in the two sites differ by roughly a 180 degrees rotation around the
      isoprenoid tail. Here we present molecular dynamics simulations, which support
      the theory of a spontaneous transfer of Q(B) between the distal site and the
      proximal site. In contrast to earlier computational studies on RCs, the molecular
      dynamics simulations of Q(B) migration resulted in a proximal Q(B) binding
      pattern identical to that of the crystallographic findings. Also, we demonstrate
      that the preference towards the proximal Q(B) location is not necessarily
      attributed to reduction of Q(B) to the semiquinone, but already to the preceding
      reduction of the primary quinone Q(A) and resulting protonation changes in the
      protein. Energy mapping of the Q(B) binding pocket indicates that the quinone
      ring rotation required for completion of the transfer between the two sites is
      improbable at the distal or proximal binding sites due to high potential
      barriers, but may be possible at a newly identified position near the distal
      binding site.

PMID- 11334793
TI  - The effects of the Na(+)/Ca(++) exchange blocker on osmotic blood-brain barrier
      disruption.
AB  - Osmotic disruption of the blood-brain barrier (BBB) by mannitol is currently
      being used to enhance drug delivery in human brains. Despite clinical and
      experimental interest, to date the time course in the early phase of disruption
      has not been accurately identified. The mechanism in barrier closure also remains
      elusive. We first studied the rapid change in cerebrovascular permeability after
      BBB disruption in rats, and then demonstrated that the Na(+)/Ca(++) exchange
      blocker (KB-R7943) prolongs osmotic disruption. Osmotic BBB disruption was
      attained by using intra-arterial infusion of hypertonic mannitol in Sprague
      Dawley (SD) rats. To measure the changes in cerebrovascular permeability,
      perfusate containing [14C]-sucrose was infused intra-arterially at different time
      points following osmotic stress. Cerebrovascular permeability was then measured
      with the in situ brain perfusion technique. This is the first in vivo study
      demonstrating that osmotic disruption is prolonged by the Na(+)/Ca(++) exchange
      blocker, which did not affect the peak level of BBB disruption. The exact time
      course of cerebrovascular reversibility was studied and the earliest BBB
      disruption was seen to occur 5 min after osmotic stress. Histopathological
      examination after osmotic disruption with the Na(+)/Ca(++) exchange blocker
      showed no neuronal damage in rat brains. Our findings represent important
      experimental information regarding pharmacological manipulation of BBB
      disruption. The possibility of prolonging the transient opening of the BBB has
      major clinical implications.

PMID- 11334794
TI  - Chronic estrogen treatment replaces striatal dopaminergic function in
      ovariectomized rats.
AB  - Eight-week-old female Sprague-Dawley rats were divided into three groups:
      ovariectomized rats (OVX); ovariectomized rats treated with estradiol valerate
      (E2), 20 microg subcutaneously (s.c.) twice weekly for 12 weeks (OVX+E2 group);
      and sham-operated control rats treated with vehicle alone (controls). Spontaneous
      locomotor activity was measured for 24 h, and then again after the administration
      of methamphetamine (1 mg/kg, i.p.). In addition, striatal contents of dopamine
      (DA) and its metabolites were measured. Using an in vivo microdialysis technique,
      changes in extracellular striatal dopamine concentration were studied in a
      separate set of similarly treated rats after the administration of
      methamphetamine (0.2 mg/kg, i.p.). Spontaneous locomotor activity decreased in
      the OVX group, and estradiol replacement reversed this decreased activity. No
      significant differences were observed in the contents of DA and its metabolites
      at the striatum among the three groups. The basal output of DA at the striatum
      was lower in the OVX group than in those of the other two groups. Extracellular
      DA concentration following methamphetamine administration was also lower in the
      rats of OVX group. These results indicate that ovariectomy decreases spontaneous
      locomotor activity, response to methamphetamine, and striatal DA release in the
      female rats. Chronic replacement of estrogen reversed spontaneous locomotor
      activity and DA release by the striatum. These results suggest that chronic
      administration of estrogen may be beneficial in the treatment of female
      menopausal patients with Parkinson's disease.

PMID- 11334795
TI  - Long-term activation of adenosine A(2a) receptors blocks glutamate excitotoxicity
      in cultures of avian retinal neurons.
AB  - Previous work showed the presence of adenosine receptors as well as adenosine
      uptake and release mechanisms in developing chick retinal neurons in culture. In
      the present work we show that exogenous glutamate or kainate promotes extensive
      cell death in these cultures which is blocked when the cultures are previously
      incubated with adenosine. Addition of glutamate or kainate to purified cultures
      of retinal neurons and photoreceptors induced massive death of cultured cells
      which was inhibited in both cases by preincubation with MK801, an NMDA
      antagonist, or DNQX, an AMPA/kainate antagonist. Cell death was also greatly
      attenuated by preincubation with adenosine plus EHNA, an adenosine deaminase
      inhibitor, NBI, an adenosine uptake blocker, the permeable cAMP analogs 8-Br cAMP
      and Sp cAMP and the A(2a) agonists CGS 21680 and DPMA, but not with the A(1)
      receptor agonist CHA. Kinetic studies performed determining the intracellular LDH
      activity showed that maximal death was observed after 8 h and in concentrations
      of glutamate as low as 50 microM. We also observed a time-dependent protective
      effect of adenosine beginning after 1 h of preincubation and reaching a maximal
      effect after 24 h, indicating its association with changes in cellular metabolism
      induced by long-term exposure of cells to the nucleoside. The results show that
      adenosine inhibits glutamate toxicity in retinal neurons through a long-term
      activation of A(2a) receptors and elevation of intracellular cyclic AMP levels.

PMID- 11334796
TI  - Corticotropin-releasing factor (CRF) or CRF binding-protein ligand inhibitor
      administration suppresses food intake in mice and elevates body temperature in
      rats.
AB  - Corticotropin-releasing factor (CRF) receptor agonist and CRF binding-protein
      (CRF-BP) ligand inhibitor peptides both activate CRF systems but exert very
      distinct functional profiles in animal models of arousal, energy balance and
      emotionality. The present studies were designed to extend the dissimilar efficacy
      profiles of central administration of a CRF agonist, r/h CRF(1-41), versus a CRF
      BP ligand inhibitor, r/h CRF(6-33), into mouse and rat models of energy balance
      in order to further explore in vivo efficacy of these ligands in two separate
      animal species. In CD-1 mice, food intake was significantly attenuated 3 h after
      acute administration of CRF(1-41) (0.007-0.2 nmol), but not CRF(6-33). In obese
      Ob/Ob mice, both CRF(1-41) (0.007-0.2 nmol) and CRF(6-33) (0.02-2.3 nmol)
      significantly attenuated basal feeding over 3 h following acute peptide
      administration. In rats, CRF(1-41) (1 nmol) and CRF(6-33) (1.5-7.7 nmol) infusion
      significantly increased rectal temperature. In studies employing a telemetry
      apparatus, core temperature was also increased by CRF(1-41) (1 nmol) and CRF(6
      33) (1.5 nmol), whereas only CRF(1-41) increased locomotor activity and heart
      rate. These results suggest that CRF receptor agonist administration is capable
      of producing a global profile of negative energy balance by reducing food intake
      in mice and increasing energy expenditure in rats. In contrast, CRF-BP ligand
      inhibitor administration appears to suppress food intake in a mouse strain
      selective manner and to elevate rectal and core temperature in rats without
      accompanying cardiovascular activation.

PMID- 11334797
TI  - Further evidence that extracellular serotonin in the rostral ventrolateral
      medulla modulates 5-HT(1A) receptor-mediated attenuation of exercise pressor
      reflex.
AB  - We determined changes in extracellular levels of glutamate, serotonin (5-HT),
      norepinephrine (NE), and dopamine (DA) within rostral ventrolateral medulla
      (RVLM) during 5-HT(1A)-receptor stimulation-mediated inhibition of cardiovascular
      responses to static muscle contraction using anesthetized rats. In ten rats,
      muscle contraction significantly increased (P<0.01) mean arterial pressure (MAP)
      by 29+/-4 mm Hg, heart rate (HR) by 25+/-3 bpm, and glutamate levels by 4.5+/-0.8
      ng/5 microl. Microdialysis of a 5-HT(1A) receptor agonist, 8-OH-DPAT (10 mM),
      into the RVLM for 30 min attenuated cardiovascular responses to muscle
      contraction and had no effect on glutamate levels. A subsequent administration of
      10 mM WAY100635, a 5-HT(1A) antagonist, into the RVLM antagonized the attenuating
      effects of 8-OH-DPAT. In another ten rats, muscle contraction significantly
      increased (P<0.01) MAP and HR by 20+/-2 mmHg and 25+/-8 bpm, respectively. In
      addition, levels of 5-HT, NE, and DA in the RVLM significantly increased (P<0.01)
      by 3.6+/-0.3, 3.2+/-0.3, and 3.3+/-0.4 pg/10 microl, respectively. Administration
      of 8-OH-DPAT (10 mM) into the RVLM for 30 min attenuated cardiovascular responses
      to muscle contraction and had no effects on NE and DA levels. However, the drug
      significantly attenuated 5-HT levels following a muscle contraction.
      Microdialysis of 10 mM WAY100635 into the RVLM reversed both cardiovascular and 5
      HT changes. These results suggest that stimulation of 5-HT(1A)-receptors within
      the RVLM attenuates cardiovascular responses to static exercise via a reduction
      of extracellular 5-HT concentration and most likely not through changes in
      glutamate, NE or DA levels.

PMID- 11334798
TI  - Morphometric multivariate analysis of GABAergic neurons containing calretinin and
      neuronal nitric oxide synthase in the mouse hippocampus.
AB  - Several studies reported the morphology of calretinin-positive (CR+) neurons and
      nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) labeled or
      neuronal nitric oxide synthase-positive (nNOS+) neurons in the rodent
      hippocampus, where these neurons showed similar morphological features. In
      addition, a previous study reported the frequent colocalization of CR and NADPH-d
      in the rat hippocampus. In this study, we aimed to examine whether CR+ neurons
      and nNOS+ neurons belong to a same morphological subpopulation of GABAergic
      neurons in the mouse hippocampus. Neurons were immunocytochemically classified
      into three groups, i.e., CR+/nNOS-, CR-/nNOS+ and CR+/nNOS+ groups. The present
      morphometric analysis was performed in the mouse Ammon's horn, because CR+/nNOS+
      neurons were rarely found in the mouse dentate gyrus. We selected three
      morphometric parameters, i.e., soma area, soma form factor (FF) and number of
      primary dendrites. Dunnett's post-hoc analysis revealed that soma area, soma FF
      and number of primary dendrites were significantly larger in CR-/nNOS+ group than
      in CR+/nNOS- and CR+/nNOS+ groups. The morphometric data of CR+/nNOS+ group were
      quite similar to those of CR+/nNOS- group. The morphometric multivariate logistic
      regression analysis revealed that these three morphometric parameters were
      independent significant variables to discriminate between CR+/nNOS- and CR-/nNOS+
      groups, and the majority of CR+/nNOS- and CR-/nNOS+ groups were correctly
      classified from the morphometric features. The present results clearly indicate
      that CR+/nNOS- neurons and CR-/nNOS+ neurons belong to different morphological
      subpopulations, and lead us to speculate that they might play different
      functional roles in the hippocampal circuit. The further application of
      morphometric multivariate analysis would be valuable to understand the functional
      roles of chemically defined neurons in the various brain regions.

PMID- 11334799
TI  - Epithelial adhesion complexes and organ culture of the human cornea.
AB  - The effects of extended organ culture of human cornea on the structural
      integrity, particularly adhesion complexes, of the epithelium were determined.
      Human corneas were placed in organ culture using an immersion method. The
      structure of the cornea prior to culture (0 h) and at 7, 14, and 18 days in
      culture was evaluated by staining with hematoxylin/eosin, and by ultrastructural
      analysis that included a morphometric study of the type and number of adhesion
      complexes. Human corneas prepared immediately (0 h) and those in culture after 7
      days showed similar structural organization and anatomical features. In contrast
      to 0 h specimens, the corneal epithelium at 14 days in culture exhibited signs of
      deterioration, with increases in cellular contraction, extracellular space,
      electron density of the cytoplasm, nuclear invaginations, and nucleoplasmic
      opacity, as well as aggregations of junctional complexes between cells. At 18
      days in culture, the ocular surface epithelium was markedly reduced in thickness
      and consisted of no more than 2-3 cell layers; a distinct basal layer was not
      detected, and the morphology of the suprabasal and basal layers were similar. The
      basement membrane was disorganized, and anchoring complexes composed of
      hemidesmosomes were often absent. The number and type of the anchoring complexes
      associated with the basal epithelium and Bowman's membrane were comparable until
      14 days of age, although the total number of hemidesmosomes per microm of
      epithelial plasmalemma was subnormal. After 2 weeks in culture, there were 38-72%
      fewer anchoring complexes and a decrease of 44% in the number of
      hemidesmosomes/microm of membrane from samples prepared immediately and after 7
      days in culture. These results indicate that the structural integrity of human
      corneal epithelium in organ culture is compromised after 14 days in vitro using
      an immersion system of tissue culture. Thus, long-term use of cultures to define
      homeostasis and wound healing of the ocular surface epithelium, which
      necessitates normal architecture including anchoring complexes between epithelium
      and Bowman's membrane, may not be appropriate and requires careful monitoring
      both qualitatively and quantitatively at the electron microscopic level of
      resolution.

PMID- 11334800
TI  - Effects of olfactory bulbectomy on NMDA receptor density in the rat brain:.
AB  - Olfactory bulbectomy (OBX) transects the glutamatergic efferents from the
      olfactory bulbs, and the changes of glutamatergic N-methyl-D-aspartate (NMDA)
      receptor-mediated function are though to be involved in the behavioral deficits
      seen in OBX rats. In the present study, irritability scores in OBX male Wistar
      rats were correlated with discrete regional effects on NMDA receptor function
      measured using a [3H] MK-801 binding assay. Irritability scores, measured before
      and for 2 weeks after OBX, showed a gradual increase in irritability after OBX. A
      reduction of the NMDA receptor density was observed in the cerebral cortex and
      amygdala 16 days after OBX, but not in the striatum, olfactory tubercle,
      entorhinal cortex, and hippocampus. These results demonstrate that OBX causes
      changes in the NMDA receptor system in certain brain regions and suggest that
      these changes may be responsible for the behavioral deficits of OBX rats.

PMID- 11334801
TI  - Ethanol-induced swelling in neonatal rat primary astrocyte cultures.
AB  - We tested the hypothesis that astrocytes swell in response to ethanol (EtOH)
      exposure. The experimental approach consisted of an electrical impedance method
      designed to measure cell volume. In chronic experiments, EtOH (100 mM) was added
      to the culture media for 1, 3, or 7 days. The cells were subsequently exposed for
      15 min to isotonic buffer (122 mM NaCl) also containing 100 mM EtOH.
      Subsequently, the cells were washed and exposed to hypotonic buffer (112 mM NaCl)
      containing 100 mM mannitol. Chronic exposure to EtOH led to a marked increase in
      cell volume compared with control cells. Specific anion cotransport blockers,
      such as SITS, DIDS, furosemide, or bumetanide, when simultaneously added with
      EtOH to hyponatremic buffer, failed to reverse the EtOH-induced effect on
      swelling. In acute experiments, confluent neonatal rat primary astrocyte cultures
      were exposed to isotonic media (122 mM NaCl) for 15 min, followed by 45-min
      exposure to hypotonic media (112 mM NaCl, mimicking in vivo hyponatremic
      conditions associated with EtOH withdrawal) in the presence of 0-100 mM EtOH.
      This exposure led to a concentration-dependent increase in cell volume. Combined,
      these studies suggest that astrocytes exposed to EtOH accumulate compensatory
      organic solutes to maintain cell volume, and that in response to hyponatremia and
      EtOH withdrawal their volume increases to a greater extent than in cells exposed
      to hyponatremia alone. Furthermore, the changes associated with EtOH are osmotic
      in nature, and they are not reversed by anion cotransport blockers.

PMID- 11334802
TI  - Increased sensitivity to seizures in repeated exposures to hyperbaric oxygen:
      role of NOS activation.
AB  - Nitric oxide is involved in the mechanism of hyperbaric oxygen (HBO(2)) brain
      toxicity as nitric oxide synthase (NOS) inhibitors delay latent time before the
      onset of seizures. The purpose of this study was to investigate if seizures
      affect sensitivity to convulsions during subsequent exposure to HBO(2) and to
      determine if NOS activity and expression is changed after HBO(2) seizures. Rats
      were exposed to 5 atm (gauge pressure) 100% O(2) until seizures recorded by
      electroencephalograph (EEG) and reexposed 1, 2, or 6 days later. Latency to
      seizures was significantly shorter (P<0.05) in animals reexposed 1 or 2 days
      after the first exposure. Activity of calcium-dependent NOS activity in cortex
      was significantly higher 1 and 2 days after seizures compared with controls
      (P<0.05), while calcium-independent NOS activity was not changed during the 6-day
      post-seizure interval. The expression of neuronal NOS (nNOS) protein determined
      by Western blot was higher 1 and 2 days after seizures (P<0.05), while the
      expression of endothelial (eNOS) and inducible (iNOS) remained unchanged. nNOS
      upregulation 1 and 2 days after seizures and protection against HBO(2) seizures
      by nNOS-specific inhibitor 7-nitroindazole (7-NI) suggest possible involvement of
      NO in the mechanism of increased sensitivity to HBO(2) in reexposures.

PMID- 11334803
TI  - Modulation of pain by [1DMe]NPYF, a stable analogue of neuropeptide FF, in
      neuropathic rats.
AB  - The pain modulatory effects of (D-Tyr)L(Me-Phe)QPQRF-amide ([1DMe]NPYF), a stable
      analogue of neuropeptide FF were studied in rats with a chronic neuropathy
      induced by unilateral ligation of two spinal nerves. According to behavioral
      assessments, intrathecal (i.t.) administration of [1DMe]NPYF induced mechanical
      antiallodynic and thermal antinociceptive effects in a parallel and dose
      dependent fashion, whereas following administration in the periaqueductal gray
      (PAG) it produced only mechanical antiallodynia. I.t. or PAG administration of
      FLFQPQRF, a non-amidated form of NPFF, or intraplantar injection of [1DMe]NPYF
      into the neuropathic paw had no effects. Electrophysiological results indicated
      that administration of [1DMe]NPYF suppressed responses of nociceptive spinal
      dorsal horn neurons in a submodality selective way and without an effect on their
      spontaneous activity; PAG administration predominantly suppressed brush-evoked
      responses and i.t. administration heat-evoked responses. The descending
      inhibitory effect by conditioning electrical stimulation of the PAG was enhanced
      by i.t. administration of [1DMe]NPYF. The reversibility of [1DMe]NPYF-induced
      effects by naloxone (1 mg/kg subcutaneously) depended on the submodality of test
      stimulation and the route of drug administration. The amplitude of the innocuous
      H-reflex was not changed by [1DMe]NPYF administered i.t. in control rats. The
      present results indicate that [1DMe]NPYF produces a selective attenuation of pain
      in neuropathic animals due to naloxone-sensitive or -insensitive central
      mechanisms depending on the submodality of pain and route of drug administration.
      The amide-group is essential for the [1DMe]NPYF-induced attenuation of pain.

PMID- 11334804
TI  - Marked elevation in cortical urate and xanthine oxidoreductase activity in
      experimental bacterial meningitis.
AB  - Experimental bacterial meningitis due to Streptococcus pneumoniae in infant rats
      was associated with a time-dependent increase in CSF and cortical urate that was
      approximately 30-fold elevated at 22 h after infection compared to baseline. This
      increase was mirrored by a 20-fold rise in cortical xanthine oxidoreductase
      activity. The relative proportion of the oxidant-producing xanthine oxidase to
      total activity did not increase, however. Blood plasma levels of urate also
      increased during infection, but part of this was as a consequence of dehydration,
      as reflected by elevated ascorbate concentrations in the plasma. Administration
      of the radical scavenger alpha-phenyl-tert-butyl nitrone, previously shown to be
      neuroprotective in the present model, did not significantly affect either
      xanthine dehydrogenase or xanthine oxidase activity, and increased even further
      cortical accumulation of urate. Treatment with the xanthine oxidoreductase
      inhibitor allopurinol inhibited CSF urate levels earlier than those in blood
      plasma, supporting the notion that urate was produced within the brain. However,
      this treatment did not prevent the loss of ascorbate and reduced glutathione in
      the cortex and CSF. Together with data from the literature, the results strongly
      suggest that xanthine oxidase is not a major cause of oxidative stress in
      bacterial meningitis and that urate formation due to induction of xanthine
      oxidoreductase in the brain may in fact represent a protective response.

PMID- 11334805
TI  - Evidence for the ability of hippocampal neurons to develop acute tolerance to
      ethanol in behaving rats.
AB  - BACKGROUND: The cellular mechanisms underlying acute tolerance to alcohol are
      unclear. This study aimed to determine whether hippocampal neurons have the
      ability to develop acute tolerance to alcohol in behaving rats. METHODS:
      Intrahippocampal microdialysis was performed in freely behaving rats, and the
      firing of single neurons in the dialysis area was recorded. The control
      microdialysis fluid, artificial cerebrospinal fluid (ACSF), was replaced with 1 M
      ethanol in ACSF for a 30 min period. One hour later, the ethanol perfusion was
      repeated. To test the functional integrity of the microdialysis probe in situ,
      each microdialysis session was completed with recording the effect of a 10-20 min
      perfusion of 500 microM N-methyl-D-aspartate (NMDA). The extracellular
      concentration profile of ethanol during intrahippocampal microdialysis with 1 M
      ethanol was estimated in a separate study in anesthetized rats. The ethanol
      content was measured in tissue slices surrounding the probe with gas
      chromatography (GC), and the generated data were analyzed with a mathematical
      model for microdialysis to estimate the concentration of ethanol at the recording
      site. RESULTS: The predominant effect of the first intrahippocampal microdialysis
      with ethanol was a decrease in firing rate in both pyramidal cells and
      interneurons. In contrast, such firing rate decrease did not develop during the
      second ethanol perfusion. Subsequent NMDA perfusion still induced robust changes
      in the electrical activity of the neurons. The estimated extracellular ethanol
      concentration at the recording site was 45-70 mM. CONCLUSION: This study revealed
      that hippocampal neurons have the ability to develop acute tolerance to a single
      exposure of clinically relevant concentrations of ethanol in behaving rats,
      without influences from the rest of the body.

PMID- 11334806
TI  - Effects of rapid eye movement (REM) sleep deprivation on pain sensitivity in the
      rat.
AB  - The relationship between pain and sleep seems to be reciprocal: if pain may
      interrupt or disturb sleep, poor sleep can also influence pain perception.
      However the influence of sleep disturbances on pain sensitivity remain poorly
      investigated. The aim of this study was to assess the effect of REM sleep
      deprivation on the reaction of rats subjected to different noxious stimuli. In
      each experiment 16 Wistar male rats were randomly assigned to two groups:
      controls (n=8), and REM sleep deprived rats (n=8). REM sleep deprivation was
      elicited using the 'inverted flower pot' technique. Four different experiments
      were performed to assess the sensitivity to mechanical (vocalization threshold in
      paw pressure), thermal (tail withdrawal latency in hot water immersion),
      electrical (envelope of 2nd peep in tail shock test) and chemical (analgesic
      behavior in formalin test) noxious stimuli. All experiments were performed over a
      5-day period with baseline (day 1, day 2) in a dry environment and REM sleep
      deprivation (day 3, day 4 and day 5) in a wet environment. Under wet conditions,
      vocalization threshold in the paw pressure test (-20%, P=0.005), and tail
      withdrawal latency in the hot water immersion test (-21%, P=0.006) were
      significantly lower, and the envelope of 2nd peep in the tail electrical shock
      was significantly greater (+78%, P=0.009), in REM sleep deprived rats compared to
      controls. However, under wet conditions the mean duration of nociceptive
      behaviors in the formalin test did not differ between the two groups. In
      conclusion, REM sleep deprivation induces a significant increase in the
      behavioral responses to noxious mechanical, thermal and electrical stimuli in
      rats.

PMID- 11334807
TI  - Trophic factor secreting kidney cell lines: in vitro characterization and
      functional effects following transplantation in ischemic rats.
AB  - Several kidney cell lines were investigated for their ability to produce glial
      cell line-derived neurotrophic factor (GDNF). Cell line-conditioned medium was
      analyzed using ELISA and two cell lines were identified which produce GDNF in
      physiologically active concentrations. ELISA analyses revealed that conditioned
      medium from these two cell lines also contained PDGF, bFGF, TGFbeta1 and
      TGFbeta2. Both of these cell lines were then transplanted into the striatal
      penumbra of rats, 1 h following middle cerebral artery occlusion. Behavioral
      testing revealed that both cell lines reduced the deficit associated with
      cerebral ischemia and reduced the infarct volume relative to controls. Reduction
      of infarct volume was likely achieved by the action of GDNF and/or other growth
      factors produced by the cells.

PMID- 11334808
TI  - Dependence of the acid-sensitive ion channel, ASIC1a, on extracellular Ca(2+)
      ions.
AB  - The early H(+)-induced current in the embryonic spinal cord neurone depends on
      extracellular Ca(2+) for its function. We have studied the Ca(2+)-dependence of
      homo- and heteromultimeric acid-sensing ion channels (ASICs) expressed in Cos
      cells. It was found that single-channel conductance of both the ASIC2a and the
      ASIC1a channel is reduced at membrane potentials more negative than -40 mV by
      elevated extracellular Ca(2+). Due to this effect on unitary currents, the
      macroscopic ASIC2a peak current at -60 mV decreases gradually with rising
      extracellular Ca(2+) concentration. In addition, the macroscopic ASIC1a current
      is very small at low extracellular Ca(2+) and increases with rising Ca(2+) up to
      5 mM before decreasing again at still higher concentrations of extracellular
      Ca(2+).

PMID- 11334809
TI  - Phasic modulation of corticomotor excitability during passive movement of the
      upper limb: effects of movement frequency and muscle specificity.
AB  - Modulations in the excitability of spinal reflex pathways during passive rhythmic
      movements of the lower limb have been demonstrated by a number of previous
      studies [4]. Less emphasis has been placed on the role of supraspinal pathways
      during passive movement, and on tasks involving the upper limb. In the present
      study, transcranial magnetic stimulation (TMS) was delivered to subjects while
      undergoing passive flexion-extension movements of the contralateral wrist. Motor
      evoked potentials (MEPs) of flexor carpi radialis (FCR) and abductor pollicus
      brevis (APB) muscles were recorded. Stimuli were delivered in eight phases of the
      movement cycle during three different frequencies of movement. Evidence of marked
      modulations in pathway excitability was found in the MEP amplitudes of the FCR
      muscle, with responses inhibited and facilitated from static values in the
      extension and flexion phases, respectively. The results indicated that at higher
      frequencies of movement there was greater modulation in pathway excitability.
      Paired-pulse TMS (sub-threshold conditioning) at short interstimulus intervals
      revealed modulations in the extent of inhibition in MEP amplitude at high
      movement frequencies. In the APB muscle, there was some evidence of phasic
      modulations of response amplitude, although the effects were less marked than
      those observed in FCR. It is speculated that these modulatory effects are
      mediated via Ia afferent pathways and arise as a consequence of the induced
      forearm muscle shortening and lengthening. Although the level at which this input
      influences the corticomotoneuronal pathway is difficult to discern, a
      contribution from cortical regions is suggested.

PMID- 11334810
TI  - Distribution of somatostatin (SS) immunoreactivity using specific rabbit
      antibodies in preoptic-anterior hypothalamus (PO-AH) of female rat brain.
AB  - Distribution of somatostatin (SS) immunoreactivity was observed in the preoptic
      anterior hypothalamus (PO-AH) of the female rat brain. Six specific rabbit
      antibodies A (SS-14), B (SS-28), C (SS-28 complete), D (SS 14 and SS-28 both), E
      (SS preprohormone) and F (GHRH) were used for immunostaining using Avidin-Biotin
      Complex (ABC) method (Hsu et al., 1981). Immunostaining was observed with all the
      six antibodies, in the serial sections passing through various bregma levels (
      0.3 to -3.3 mm) of preoptic-anterior hypothalamic (PO-AH) region including median
      eminence (ME). In conclusion, the present study suggests that immunoreactive
      nerve terminals for both SS-14 and SS-28 are present in internal (IZ) and
      external zones (EZ) of ME. High intensity of SS-14 and SS-28 containing terminals
      in EZ suggests that both SS fractions are involved in regulating GH secretion in
      anterior pituitary. This is a first report on comparative distribution of
      immunoreactivities of four different fractions of SS, SS-preprohormone and GHRH
      in PO-AH.

PMID- 11334811
TI  - The discharge of a subset of serotonergic raphe magnus cells is influenced by
      baroreceptor input.
AB  - In order to determine whether serotonergic cells in the medullary raphe magnus
      (RM) receive baroreceptor input, cells were tested for their responses to
      descending aortic occlusion, aortic nerve stimulation, or systemic phenylephrine
      administration in the lightly anesthetized rat. Serotonergic cells were
      identified physiologically by a quantitative analysis of their slow and steady
      discharge. Greater than 40% of the serotonergic RM cells tested responded to
      brief occlusion of the descending aorta at the level of the coeliac arteries, a
      stimulus that elevated blood pressure by about 30 mmHg. Similarly, about 40% of
      the serotonergic RM cells responded to stimulation of the aortic nerve, a nerve
      that contains primarily baroreceptor afferents from the aortic arch. Greater than
      70% of RM serotonergic cells responded to phenylephrine administration which
      elevated blood pressure by an average of 50 mmHg. Serotonergic cell responses to
      all methods of baroreceptor activation were small in magnitude and were largely
      restricted in time to the stimulus duration. The results indicate that a subset
      of serotonergic cells in RM are influenced by baroreceptor activity.

PMID- 11334812
TI  - Immunohistochemical localization of a 40-kDa catecholamine regulated protein in
      the nigrostriatal pathway.
AB  - The 40 kDa catecholamine regulated protein (CRP40) has been shown to covalently
      bind catcholamines in vitro. In this report we provide evidence for CRP40
      localization in the dopaminergic nigrostriatal pathway. Using double labeling
      immunohistochemistry, CRP40 was detected in the majority of substantia nigra pars
      compacta and striatal neurons. In addition, CRP40 was also present in tyrosine
      hydroxylase immunonegative neurons. Subcellular localization of CRP40 shows a
      predominant nuclear presence in striatal neurons while distinct outlining of the
      nucleus and cell body staining were seen more readily in nigral neurons. These
      findings suggest that CRP40 may have multiple functions in a variety of neurons
      in the central nervous system.

PMID- 11334813
TI  - Baclofen inhibition of dorsal root-evoked inhibitory postsynaptic currents in
      substantia gelatinosa neurons of rat spinal cord slice.
AB  - We investigated the action of baclofen, an agonist for GABA(B) receptor, on the
      dorsal root-evoked inhibitory postsynaptic currents (IPSCs) in substantia
      gelatinosa (SG) neurons in the adult rat spinal cord slice. Most of the dorsal
      root-evoked IPSCs in SG were mediated by Adelta fibers. Baclofen (10 microM)
      reduced the amplitude of Adelta fiber-evoked glycine receptor-mediated IPSCs to
      20.9+/-3.0% (n=13), and GABA(A) receptor-mediated IPSCs to 18.6+/-3.4% (n=12) of
      the controls, respectively. The results further suggest modulatory role of
      GABA(B) receptor in spinal dorsal horn.

PMID- 11334814
TI  - Effect of long-term ethanol feeding on brainstem alpha(2)-receptor binding in
      Wistar-Kyoto and spontaneously hypertensive rats.
AB  - Our previous studies have shown that ethanol attenuates baroreflex function in
      Wistar-Kyoto (WKY) but not in spontaneously hypertensive rats (SHRs). The present
      study determined the effects of chronic ethanol administration on alpha(2)
      binding sites in brainstem areas that modulate baroreflexes. In vitro
      autoradiography was utilized to evaluate the effect of a 3-month ethanol feeding
      on the density (B(max)) and affinity (K(D)) of alpha(2)-adrenoceptors in the
      middle (mNTS) and rostral (rNTS) portions of the nucleus tractus solitarius of
      SHRs and WKY rats. Autoradiographic examination of brainstem sections
      preincubated with [125I]p-iodoclonidine revealed no inter-strain differences in
      alpha(2)-binding in control rats. Ethanol feeding caused strain-dependent changes
      in alpha(2)-binding activity, which comprised significant (P<0.05) decreases in
      the density of alpha(2)-binding sites in both areas of the NTS in SHRs versus no
      effect in WKY rats. These findings do not favor a role for brainstem alpha(2)
      adrenoceptors in ethanol-induced attenuation of baroreflexes. Interestingly, the
      ethanol-evoked reduction in the NTS alpha(2)-receptor density in SHRs may explain
      reported findings that ethanol abolishes the hypotensive effect of the alpha(2)
      adrenoceptor agonist clonidine in this rat model.

PMID- 11334815
TI  - Synthesis of leukemia inhibitory factor in injured peripheral nerves and their
      cells.
AB  - The time and site of induction of leukemia inhibitory factor mRNA in injured rat
      sciatic nerves and its regulation in Schwann cells and fibroblasts from neonatal
      rat nerves were investigated. Leukemia inhibitory factor mRNA is induced at the
      lesion site within 6 h of sciatic nerve transection but only after 24 h in the
      more distal segments. In vitro, interleukin-1beta increases the concentration of
      leukemia inhibitory mRNA in nerve fibroblasts but not in Schwann cells. Changes
      in leukemia inhibitory factor mRNA concentration in injured nerves and peripheral
      nerve cells are similar to those for nerve growth factor mRNA.

PMID- 11334816
TI  - Expression of GAP-43 in the retina of rats following protracted illumination.
AB  - Distribution of GAP-43 was studied in the retinas of rats after continuous
      illumination followed by different darkness periods. GAP-43 immunoreactivity was
      maximum in regenerating outer photoreceptor segments of rats kept in total
      darkness for 10 days, while in the inner plexiform layer, immunoreactivity was
      maximum immediately after illumination. Changes in GAP-43 expression could
      participate in retinal repair/regeneration after light-induced damage.

PMID- 11334817
TI  - Nucleus basalis magnocellularis electrical stimulation facilitates two-way active
      avoidance retention, in rats.
AB  - We studied the effects of post-training intracranial electrical stimulation of
      the nucleus basalis magnocellularis on two-way active avoidance retention. After
      the acquisition, rats were stimulated for 20 min, and they were tested again
      after 24 h or 11 days. The treatment improved memory consolidation, especially in
      animals with a low initial learning ability. These facilitative effects could be
      attributed to an enhancement of cortical and/or amygdala activation, leading to
      an improvement in associative processes and/or cortical plasticity.

PMID- 11334819
TI  - Distribution and immunohistochemical characterization of torsinA immunoreactivity
      in rat brain.
AB  - A mutation of the DYT1 gene on chromosome 9q34 has recently been identified as
      the cause of one form of autosomal-dominantly inherited dystonia. TorsinA, the
      protein product of this gene, has homology with the family of heat shock
      proteins, and is found in many peripheral tissues and brain regions. We used a
      polyclonal antibody to torsinA, developed in our laboratory, to systematically
      examine the regional distribution of torsinA in rat brain. We find that neurons
      in all examined structures are immunoreactive for this protein. There is intense
      immunoreactivity in most neuronal nuclei, with slightly less labeling of
      cytoplasm and proximal processes. Terminals also are labeled, especially in
      striatum, neocortex and hippocampus. Double-labeling fluorescence
      immunohistochemistry using antibodies to neurotransmitters and other
      neurochemical markers demonstrated that the majority of neurons of all studied
      neurochemical types are immunoreactive for torsinA. Our findings indicate that
      torsinA is widely distributed in the central nervous system implicating
      additional, localized factors, perhaps within the basal ganglia, in the
      development of dystonia. Many other proteins have a similar widespread
      distribution, including some which have been implicated in other movement
      disorders and neurodegenerative processes, such as parkin, alpha-synuclein,
      ubiquitin and huntingtin. The distribution of torsinA in rat brain as
      demonstrated by immunohistochemistry contrasts with the results of in situ
      hybridization studies of torsinA mRNA in human postmortem brain in which a more
      limited distribution was found.

PMID- 11334818
TI  - Activation-induced cell death of rat astrocytes.
AB  - Inflammatory activation of astrocytes has been implicated in various
      neurodegenerative diseases. The elimination of activated astrocytes by apoptosis
      or the deactivation may be the mechanisms for auto-regulation of activated
      astrocytes. To test the possibility of apoptotic elimination of activated
      astrocytes, we examined a potential correlation between activation state of
      astrocytes and their viability using C6 rat glial cells and rat primary astrocyte
      cultures exposed to a variety of inflammatory stimuli such as lipopolysaccharide,
      interferon-gamma, and tumor necrosis factor-alpha. Nitric oxide production was
      measured to evaluate inflammatory activation of astrocytes. We found that: (i)
      the activation of astrocytes by the combination of lipopolysaccharide and
      inflammatory cytokines, but not by either alone, led to nitric oxide production
      followed by apoptotic cell death; (ii) the amount of nitric oxide produced by
      activated astrocytes was inversely proportional to the viability of the cells;
      (iii) inhibition of nitric oxide synthase by N-monomethyl L-arginine blocked
      death of activated astrocytes; and (iv) nitric oxide donors induced apoptosis of
      astrocytes in a caspase-dependent manner. Taken collectively, our results suggest
      that activated astrocytes produce nitric oxide as an autocrine mediator of
      caspase-dependent apoptosis, and this type of programmed cell death of astrocytes
      may be the underlying mechanism for the auto-regulation of inflammatory
      activation of astrocytes.

PMID- 11334821
TI  - Opportunities for sudden death prevention: directions for new clinical and basic
      research.
AB  - Sudden cardiac death (SCD) represents an enormous public health problem in all
      developed countries of the world, yet its magnitude and precise incidence in
      different populations and disease subgroups remains unclear. There also remain
      major questions and research challenges in establishing the sensitive and
      specific markers of SCD risk needed for optimizing therapeutic strategies and
      allocation of resources, such as implantable defibrillators. In the past, risk
      factors for coronary artery disease (CAD) have been heavily relied on to identify
      risk for SCD. However, although a majority of SCD events continue to occur in the
      context of this disease etiology, risk factors for CAD appear to have relatively
      limited ability to predict risk in specific individuals and subgroups with
      enhanced progressive or inherited susceptibility to lethal arrhythmias. This
      commentary is intended to assess potentials for progress in developing improved
      approaches to SCD prediction and prevention through new clinical and basic
      research on the fundamental causes of ventricular arrhythmias, the development of
      new markers of electrical instability, and better understanding of the role of
      genetic variability in their origin.

PMID- 11334822
TI  - Risk stratifiers for sudden cardiac death (SCD) in the community: primary
      prevention of SCD.

PMID- 11334823
TI  - Reducing mortality from sudden cardiac death in the community: lessons from
      epidemiology and clinical applications research.
AB  - The reduction of mortality from sudden cardiac death (SCD) in the community
      remains a challenge. Clinical-epidemiologic studies have identified a range of
      factors that are associated with an increased risk of SCD. While of potential
      etiologic and prognostic importance, these factors have limited sensitivity and a
      low positive predictive value for SCD. On the other hand, clinical trials have
      suggested that a variety of interventions, including risk factor reduction,
      nutritional interventions, drug therapies, cardiac procedures, and new
      technologies, have the potential to reduce mortality from SCD. In this review, we
      examine what is known about the epidemiology and clinical application of
      interventions to reduce mortality from SCD; and, we consider the impact of both
      prevention and clinical interventions on mortality from SCD from a community
      perspective. There is mounting evidence that supports both public health and
      clinical efforts to prevent the occurrence of SCD. There also is evidence
      suggesting that new technologies, such as automated external defibrillators, have
      the potential to reduce case-fatality from SCD. Further progress will depend on
      improved methods to identify persons-at-risk, reduction of risk factors, and
      application of techniques -- both simple and advanced -- to improve survival in
      victims of SCD.

PMID- 11334824
TI  - Sudden cardiac death: role of heart rate variability to identify patients at
      risk.

PMID- 11334825
TI  - Concealed arrhythmogenic syndromes: the hidden substrate of idiopathic
      ventricular fibrillation?
AB  - In approximately 6--10% of survivors of cardiac arrest no cardiac abnormality can
      be identified despite extensive clinical evaluation. Autopsy data confirm that in
      a similar percentage of victims of sudden death no structural heart disease can
      be identified at post mortem evaluation. Occurrence of cardiac arrest in the
      absence of a substrate is defined 'idiopathic ventricular fibrillation' thus
      admitting that the cause for the arrhythmic event has remained unknown. We
      present data supporting the hypothesis that incompletely penetrant genetic
      defects may underlie at least some of these unexplained deaths.

PMID- 11334826
TI  - Pharmacogenetics and drug-induced arrhythmias.
AB  - Drugs are widely recognized to vary in the beneficial and undesirable effects
      they produce in human subjects. The understanding that variants (polymorphisms
      and mutations) in the human genome are common and may well modulate both disease
      and its response to drugs, is a critical new concept in understanding mechanisms
      of drug action and their variability in human subjects. Variability can arise
      because of variability in genes encoding molecules of drug disposition, in genes
      encoding molecules that drugs target, or in genes that modulate the overall
      activity of the complex biological systems within which drugs act. The evolving
      understanding of the genetic basis of variability in response to drugs used in
      the treatment of sudden cardiac death has important implications not only for the
      treatment of patients who have survived an episode, but also for helping
      formulate a framework for further understanding mechanisms of drug action at the
      genetic level.

PMID- 11334827
TI  - What do implantable cardioverter/defibrillators teach us about the mechanisms of
      sudden cardiac death?
AB  - Almost two decades of experience with the ICD have resulted in a better
      understanding of the nature of life-threatening ventricular tachyarrhythmias. The
      most pertinent achievements in this respect stem from clinical follow-up
      observations in patients with important clinical entities such as dilated
      cardiomyopathy or the Brugada syndrome. For instance, patients with dilated
      cardiomyopathy presenting with syncope and a negative electrophysiological study
      have been shown to have a high incidence of appropriate usage of their ICD. On
      the other hand, relative little has been gained from the extensive electrogram
      storage capabilities of third and fourth generation ICDs. Basically, careful
      evaluation of these electrograms has confirmed previous anecdotal data obtained
      from analysis of Holter recordings of patients who died suddenly while wearing
      the ECG recorder. In most instances, VT/VF episodes are triggered by relatively
      late-coupled premature beats whereas short--long--short sequences have been
      observed only in few patients. One future research avenue concerns the more
      detailed analysis of changes in cardiac autonomic tone preceding the occurrence
      of sustained ventricular tachyarrhythmias which can be assessed from the
      electrogram storage of the ICD.

PMID- 11334828
TI  - Mechanisms underlying ventricular tachycardia and its transition to ventricular
      fibrillation in the structurally normal heart.
AB  - Reentrant ventricular tachycardia (VT) is the most common sustained arrhythmia
      leading to ventricular fibrillation (VF). However, despite more than a century of
      research, the mechanism(s) of the conversion from reentrant VT to VF have not
      been elucidated. Based on their different electrocardiographic appearance,
      reentrant VT and VF have traditionally been thought of as resulting from two
      widely different mechanisms. Whereas VT is seen as a rapid but well organized
      process whereby the excitation wave rotates about a single well-defined circuit,
      fibrillation has been described as turbulent cardiac electrical activity,
      resulting from the random and aperiodic propagation of multiple independent
      wavelets throughout the cardiac muscle. Recently, the application of concepts
      derived from the theory of non-linear dynamics to the problem of wave propagation
      in the heart and the advent of modern high-resolution mapping techniques, have
      led some investigators to view VT and VF in terms of a single mechanism, whereby
      the self-organization of electrical waves forms 'rotors' that give rise to
      rapidly rotating spiral waves and results in either VT or VF, depending on the
      frequency of rotation and on the interaction of wave fronts with the cardiac
      muscle. As such, monomorphic VT is thought to result from a stationary rotor,
      whose frequency of rotation is within a range that allows 1:1 excitation of both
      ventricles. On the other hand, VF is thought to result from either a single
      rapidly drifting rotor, or a stationary rotor whose frequency of excitation is
      exceedingly high, thus resulting in multiple areas of intermittent block and
      giving rise to complex patterns of propagation with both deterministic and
      stochastic components. This article reviews the prevailing theories for the
      maintenance of VF, and discusses recently proposed mechanisms underlying
      transitions between VT and VF.

PMID- 11334829
TI  - Cellular mechanism of reentry induced by a strong electrical stimulus:
      implications for fibrillation and defibrillation.
AB  - The objective of this review article is to describe the graded response
      hypothesis of reentry induced by a strong single electrical stimulus in the
      normal canine ventricular myocardium. It is shown that the graded responses
      (subthreshold depolarization during phase 3 of the action potential) induced at a
      site distant (S2) from the regular S1--S1 pacing site, propagate slowly over
      short distances (approximately 5 mm) and initiate a regenerative action
      potentials in recovered cells near the S1 site. Activation wave then blocks near
      the S2 site (unidirectional block) but reenters when the S2 site recovers it
      excitability. Super strong S2 currents do not induce reentry (upper limit of
      vulnerability). Since similar activation sequence and properties are shown to
      exist in intact canine hearts during induction of ventricular fibrillation with a
      similar S2 stimulus, the graded response hypothesis may have relevance to
      vulnerability to fibrillation. Furthermore, since the upper limit of
      vulnerability is closely related to defibrillation threshold, the graded response
      hypothesis might also be relevant to defibrillation mechanism. Other proposed
      mechanisms of fibrillation and defibrillation (critical point hypothesis, the
      progressive depolarization hypothesis and the hypothesis of phase singularity of
      defibrillation failure) are also discussed in this review paper and compared to
      the graded response hypothesis.

PMID- 11334830
TI  - The role of altered intercellular coupling in arrhythmias induced by acute
      myocardial ischemia.

PMID- 11334831
TI  - Mechanoelectric contributions to sudden cardiac death.

PMID- 11334832
TI  - Sudden cardiac death by Commotio cordis: role of mechano-electric feedback.
AB  - Moderate pre-cordial mechanical impact can cause sudden cardiac death, even in
      the absence of morphological damage to the heart. This is the most severe
      expression of a condition termed, in the 19th century, Commotio cordis.
      Experimental studies performed in the early 1930s showed that sudden cardiac
      death after chest impact is brought about by an intrinsic cardiac response to the
      mechanical stimulus. The precise (sub-)cellular mechanisms of this response are
      still poorly understood. This article summarises experimental findings on the
      condition and relates them to the more recently established concept of cardiac
      mechano-electric feedback. As a result, an explanation of the mechanisms that
      give rise to sudden cardiac death by Commotio cordis and targets for further
      research are suggested.

PMID- 11334833
TI  - Postmortem diagnosis in sudden cardiac death victims: macroscopic, microscopic
      and molecular findings.

PMID- 11334834
TI  - Cellular consequences of HERG mutations in the long QT syndrome: precursors to
      sudden cardiac death.
AB  - BACKGROUND: A variety of mutations in HERG, the major subunit of the rapidly
      activating component of the cardiac delayed rectifier I(Kr), have been found to
      underlie the congenital Long-QT syndrome, LQT2. LQT2 may give rise to severe
      arrhythmogenic phenotypes leading to sudden cardiac death. OBJECTIVE: We attempt
      to elucidate the mechanisms by which heterogeneous LQT2 genotypes can lead to
      prolongation of the action potential duration (APD) and consequently the QT
      interval on the ECG. METHODS: We develop Markovian models of wild-type (WT) and
      mutant I(Kr) channels and incorporate these models into a comprehensive model of
      the cardiac ventricular cell. RESULTS: Using this virtual transgenic cell model,
      we describe the effects of HERG mutations on the cardiac ventricular action
      potential (AP) and provide insight into the mechanism by which each defect
      results in a net loss of repolarizing current and prolongation of APD.
      CONCLUSIONS: This study demonstrates which mutations can prolong APD sufficiently
      to generate early afterdepolarizations (EADs), which may trigger life-threatening
      arrhythmias. The severity of the phenotype is shown to depend on the specific
      kinetic changes and how they affect I(Kr) during the time course of the action
      potential. Clarifying how defects in HERG can lead to impaired cellular
      electrophysiology can improve our understanding of the link between channel
      structure and cellular function.

PMID- 11334835
TI  - Transgenic mice overexpressing human KvLQT1 dominant-negative isoform. Part I:
      Phenotypic characterisation.
AB  - OBJECTIVES: The KCNQ1 gene encodes the KvLQT1 potassium channel, which generates
      in the human heart the slow component of the cardiac delayed rectifier current,
      I(Ks). Mutations in KCNQ1 are the most frequent cause of the congenital long QT
      syndrome. We have previously cloned a cardiac KCNQ1 human isoform, which exerts a
      strong dominant-negative effect on KvLQT1 channels. We took advantage of this
      dominant-negative isoform to engineer an in vivo model of KvLQT1 disruption,
      obtained by overexpressing the dominant-negative subunit under the control of the
      alpha-myosin heavy chain promoter. RESULTS: Three different transgenic lines
      demonstrated a phenotype with increasing severity. Functional suppression of
      KvLQT1 in transgenic mice led to a markedly prolonged QT interval associated with
      sinus node dysfunction. Transgenic mice also demonstrated atrio-ventricular block
      leading to occasional Wenckebach phenomenon. The atrio-ventricular block was
      associated with prolonged AH but normal HV interval in His recordings. Prolonged
      QT interval correlated with prolonged action potential duration and with reduced
      K(+) current density in patch-clamp experiments. RNase protection assay revealed
      remodeling of K(+) channel expression in transgenic mice. CONCLUSIONS: Our
      transgenic mouse model suggests a role for KvLQT1 channels not only in the mouse
      cardiac repolarisation but also in the sinus node automaticity and in the
      propagation of the impulse through the AV node.

PMID- 11334836
TI  - Transgenic mice overexpressing human KvLQT1 dominant-negative isoform. Part II:
      Pharmacological profile.
AB  - OBJECTIVE: The acquired long QT syndrome results most often from the action of
      I(Kr) blocking-drugs on cardiac repolarization. We have evaluated a transgenic
      (TG) mouse (FVB) overexpressing a dominant-negative KvLQT1 isoform, as an in vivo
      screening model for I(Kr) blocking drugs. RESULTS: In TG mice, six-lead ECGs
      demonstrated sinus bradycardia, atrioventricular block, and QTc prolongation.
      Various drugs were injected intraperitoneally after blockade of the autonomic
      nervous system and serial ECGs were recorded. The end of the initial rapid phase
      of the T wave corrected for heart rate using a formula for mouse heart (QTrc),
      was used as a surrogate for the QT interval. Dofetilide, a specific I(Kr)
      blocker, did not prolong the QTrc interval either in TG or in wild-type (WT) mice
      but dose-dependently lengthened the sinus period in TG mice but not in WT mice.
      Other I(Kr) blockers including E 4031, haloperidol, sultopride, astemizole,
      cisapride and terikalant behaved similarly to dofetilide. Tedisamil, a blocker of
      the transient outward current, dose-dependently prolonged the QTrc in WT mice but
      not in TG mice and also reduced the sinus rhythm in both WT and TG mice.
      Lidocaine dose-dependently shortened the QTrc interval in TG mice and also
      lengthened the P wave duration. Nicardipine dose-dependently shortened QTrc and
      also produced sinus arrest in both WT and TG mice. CONCLUSIONS: We conclude that
      KvLQT1-invalidated TG mice discriminates in vivo drugs that blocks I(Kr) from
      drugs that block the transient outward current, the sodium current or the calcium
      current.

PMID- 11334837
TI  - Interactions between antiarrhythmic drugs and cardiac memory.
AB  - OBJECTIVE: Ventricular pacing or arrhythmias can induce cardiac memory (CM). We
      hypothesized that clinically administered antiarrhythmic drugs alter the
      expression of CM, and that the repolarization changes characteristic of CM can
      modulate the effects of antiarrhythmic drugs. METHODS: We studied conscious,
      chronically-instrumented dogs paced for two 1-h periods to study the effects of
      drugs on the evolution of memory (protocol 1) or for 21 days (protocol 2) to
      observe the effects of steady-state memory on drug actions. Dogs were treated in
      both settings with quinidine, lidocaine or E4031, in random order, and within
      therapeutic serum concentration ranges. RESULTS: Pacing, alone, for 2 h
      significantly prolonged ERP only near the left ventricular pacing site, whereas
      pacing alone for 21 days prolonged ERP at all sites (P<0.05). Quinidine and
      E4031, but not lidocaine, prolonged repolarization and ERP and suppressed
      evolution of CM in protocol 1. However, quinidine's effect in prolonging
      repolarization was diminished in both protocols, while its effect in prolonging
      ERP was diminished in the 21-day protocol only. In contrast, the effects of E4031
      were additive to those of CM, prolonging repolarization and ERP in both
      protocols, while lidocaine showed no changes in effect at all. CONCLUSIONS:
      Pacing to induce CM significantly affects ventricular repolarization and
      refractoriness, and there are interactions between CM, quinidine and E4031.
      Depending on the specific drug, these interactions have the potential to be anti-
      or proarrhythmic, and may impact importantly on the clinical efficacy of drugs as
      well as on electrophysiologic testing of drug actions.

PMID- 11334838
TI  - Phase 2 prolongation, in the absence of instability and triangulation,
      antagonizes class III proarrhythmia.
AB  - OBJECTIVE: To evaluate whether prolongation of the plateau of the action
      potential duration, in the absence of instability and triangulation, can reverse
      the proarrhythmia elicited by a class III antiarrhythmic agent. METHODS: The
      effects of almokalant, erythromycin and their combination, on cardiac
      electrophysiological parameters (action potential duration (APD), instability,
      triangulation and ectopics) were evaluated in isolated hearts from female albino
      rabbits. In this study, proarrhythmia was estimated quantitatively by number of
      ectopic beats. RESULTS: Erythromycin lengthened the APD primarily by a
      prolongation of the plateau, while having only minor effects upon phase 3
      repolarization. The prolongation did not induce much instability, triangulation
      or reverse use dependence and, as expected, erythromycin did not induce
      significant proarrhythmia. Almokalant also lengthened APD, but it did not
      lengthen the plateau; instead, it prolonged phase 3 repolarization. The
      prolongation markedly triangulated the action potential, elicited much
      instability and marked reverse use dependence. This combination of effects
      induced very marked proarrhythmia. When almokalant and erythromycin were
      combined, their effects upon APD appeared additive: both the plateau and the
      repolarization phase were prolonged. However, the larger prolongation of APD did
      not lead to more proarrhythmia; this suggests that a prolongation of APD is not
      proarrhythmic per se. On the contrary, proarrhythmia as a function of APD
      prolongation was reduced in the presence of erythromycin (P<0.05). CONCLUSION:
      Instability plus triangulation consistently lead to serious proarrhythmia
      especially when combined with reverse use dependence, but prolongation of APD in
      itself is not necessarily proarrhythmic. In fact, APD prolongation in the absence
      of instability and triangulation can be antiarrhythmic.

PMID- 11334839
TI  - Electrophysiological parameters indicative of sudden cardiac death in the dog
      with chronic complete AV-block.
AB  - BACKGROUND: The dog model of chronic complete AV-block (CAVB) demonstrates a
      considerable incidence of (witnessed) sudden death (16/117 dogs). In this study
      we tried to: (1) elucidate the mechanisms of sudden death using an ECG telemetry
      device and (2) identify retrospectively the risk parameters indicative of this
      arrhythmogenic death. METHODS: Between 1994 and 1998, 78 anesthetized dogs
      underwent an extensive electrophysiological study including: (1) left- (LV) and
      right ventricular (RV) monophasic action potential (MAP) recordings to assess
      Delta MAPD (LV APD minus RV APD) and (2) pacing protocols (PES) to induce torsade
      de pointes arrhythmias (TdP) at 4--6 weeks CAVB. Eight animals experienced sudden
      cardiac death (SCD) during the follow-up period (mean 7+/-3 weeks CAVB). Since
      the response of the CAVB dog to class III drugs is not uniform we also made
      comparisons among the SCD group, TdP drug responders and non-responders. For this
      purpose we selected all animals which (1) received almokalant (n=15, 0.12 mg/kg/5
      min) or ibutilide (n=9, 0.025 mg/kg/5 min) as an additional challenge to induce
      TdP and (2) had a follow-up period of at least 4 weeks. RESULTS: Six out of eight
      SCD dogs showed inducible TdP at baseline. Two of eight dogs had telemetric ECG
      surveillance and both revealed polymorphic VT as the cause of SCD. Baseline Delta
      MAPD of the SCD (90+/-15 ms) was significantly higher than the non-SCD group
      (n=70, 60+/-30 ms). Of the 24 dogs which received class III drugs, 12 belonged to
      the TdP responder group. Delta MAPD of the TdP responder group (80+/-15 ms) was
      similar to the SCD group and significantly higher compared to the non-responder
      group (n=12, 40+/-25 ms). QT-time and cycle length of idioventricular rhythm were
      not different. CONCLUSION: In the CAVB dog model, SCD is (1) most probably
      related to TdP while (2) inducible TdP and the measure of Delta MAPD at baseline
      indicate susceptibility to SCD.

PMID- 11334840
TI  - Late ventricular arrhythmias during acute regional ischemia in the isolated blood
      perfused pig heart. Role of electrical cellular coupling.
AB  - OBJECTIVE: Acute ischemia comes with two phases of life-threatening arrhythmias,
      early (within 10 minutes, 1A) and late (after about 15 minutes, 1B). The
      mechanism of the latter is unknown and in this paper, we test the hypothesis that
      a phase of intermediate coupling between surviving epicardium and inexcitable
      midmyocardium underlies 1B arrhythmias. METHODS: Pig hearts (n=26) were
      retrogradely perfused with a blood Tyrode's mixture. The left anterior descending
      artery was occluded. We investigated (1) inducibility of ventricular fibrillation
      (VF) with programmed stimulation, (2) tissue impedance (Rt) heterogeneity within
      the ischemic zone, (3) multiple subepicardial and midmyocardial electrograms, (4)
      subepicardial lactate dehydrogenase (LDH) and glycogen content. RESULTS: In nine
      of ten hearts, one--three premature stimuli caused VF between 14 and 53 min of
      ischemia. This typically happened when the Rt of the ischemic zone had increased
      up to 40% of its final value. More uncoupling terminated the period of VF
      inducibility. The excitability of the surviving subepicardial layer was depressed
      during the same period with partial uncoupling, but recovered when the uncoupling
      from the midmyocardium had progressed further. CONCLUSIONS: We show that 1B-VF
      can be induced within a distinct time window and coincides with a distinct range
      of Rt rise. Subepicardium is electrically depressed, presumably through coupling
      with midmyocardium, complete uncoupling causes subepicardial recovery and
      terminates the substrate for 1B-VF. Hence, we suggest that the substrate for 1B
      VF consists of intermediate coupling of subepicardium and midmyocardium.

PMID- 11334841
TI  - Resting heart rate as a predictive risk factor for sudden death in middle-aged
      men.
AB  - OBJECTIVE: A relative hyperadrenergic tone related to abnormalities of the
      autonomic nervous system is suspected in the mechanisms of sudden death.
      Therefore, we assessed the role of an elevated basal heart rate in the occurrence
      of sudden death in a long-term cohort study. METHODS: 7746 subjects aged 42--53
      years, underwent ECG and physical examination conducted by a physician under
      standardized conditions, provided blood samples for laboratory tests, and
      answered questionnaires administered by trained interviewers. The vital status
      was obtained from specific inquiries up to the time of retirement and then by
      death certificates. Men with known ischemic heart disease were further excluded
      from analysis which was conducted on the 7079 remaining subjects. RESULTS: After
      an average follow-up period of 23 years, there were 2083 deaths, among which were
      603 cardiovascular deaths including 118 sudden deaths and 192 following
      myocardial infarction. The crude risk of sudden death increased linearly with the
      level of resting heart rate and the risk in men in the highest quintile of heart
      rate was 3.8 fold than in those in the lowest quintile, whereas rates were
      approximatively twice higher for fatal myocardial infarction, cardiovascular and
      total mortality (all P<0.01). When age, body mass index, systolic blood pressure,
      tobacco consumption, parental history of myocardial infarction and parental
      history of sudden death, cholesterol level, diabetic status, and sport activity
      were simultaneously entered into the survival model, resting heart rate remained
      an independent risk factor for sudden death (P=0.03) but not for fatal myocardial
      infarction. CONCLUSION: An elevated heart rate at rest was confirmed as an
      independent risk factor for sudden death in middle-aged men.

PMID- 11334842
TI  - Increased QT dispersion in patients with Prinzmetal's variant angina and cardiac
      arrest.
AB  - OBJECTIVES: We sought to compare QT dispersion in patients presenting with
      Prinzmetal's variant angina complicated by cardiac arrest or syncope and patients
      with uncomplicated variant angina. BACKGROUND: Despite the usually benign course
      of treated Prinzmetal's variant angina, a proportion of vasospastic angina
      patients develop ventricular arrhythmias and sudden death in association with
      coronary spasm. Increased QT dispersion has been suggested to increase
      susceptibility to ventricular arrhythmias in patients with coronary artery spasm.
      METHODS: We studied 25 consecutive patients (mean age 58 years; 14 men) with
      classical Prinzmetal's variant angina and documented coronary artery spasm. None
      of the patients had coronary artery stenoses < or =40%. Five patients had
      suffered a documented cardiac arrest, two had recurrent syncope and 18 had no
      arrhythmic events or syncopal episodes. In all patients QT dispersion (QT maximum
      QT minimum in every ECG lead) was measured on the baseline 12-lead
      electrocardiogram at study entry using a digitising board. RESULTS: Mean (+/
      S.D.) QT dispersion of study patients was 62.3+/-19.5 ms. QT dispersion in
      patients with cardiac arrest and syncope (79.4+/-17.3 ms) was significantly
      higher compared to patients with no such events (56.3+/-16.9 ms), (95% CI 7.5
      38.8, P=0.005). No significant clinical, biochemical or angiographic differences
      were found between patients with and those without cardiac arrest or syncope.
      CONCLUSION: QT dispersion is increased in patients with Prinzmetal's variant
      angina complicated by cardiac arrest and syncope compared to patients without
      such events. Increased QT dispersion may be both a substrate for sudden cardiac
      death and a marker of risk in patients with Prinzmetal's variant angina.

PMID- 11334843
TI  - Non-invasive testing of acquired long QT syndrome: evidence for multiple
      arrhythmogenic substrates.
AB  - BACKGROUND: Although well-defined clinically and electrocardiographically,
      Acquired Long QT Syndrome (LQTS) remains elusive from a pathophysiologic point of
      view. An increasingly accepted hypothesis is that it represents an attenuated
      form of Congenital Long QT Syndrome. To test this hypothesis further, we
      investigated patients with Acquired LQTS, using various investigations that are
      known to give information in patients with Congenital LQTS. METHODS: All the
      investigations were performed in patients with a history of Acquired Long QT
      Syndrome, defined by marked transient QT lengthening (QT>600 ms) and/or torsades
      de pointes. Measurement of the QT interval dispersion, the interlead difference
      for the QT interval on a 12-lead ECG, was performed in 18 patients and compared
      with 18 controls, matched for age and sex. To assess sympathetic myocardial
      innervation, I-123 Meta-iodobenzylguanidine (I-123-MIBG) scintigraphy was
      performed in 12 patients, together with Thallium scintigraphy, to rule out
      abnormal myocardial perfusion. Time-frequency analysis of a high-resolution ECG
      using a wavelet technique, was made for nine patients and compared with 38
      healthy controls. Finally, genetic studies were performed prospectively in 16
      consecutive patients, to look for HERG, KCNE1, KCNE2 and KCNQ1 mutations. The
      functional profile of a mutated HERG protein was performed using the patch-clamp
      technique. RESULTS: Compared with the control group, a significant increase in QT
      dispersion was observed in the patients with a history of Acquired LQTS (55+/-15
      vs. 33+/-9 ms, P<0.001). In another group of patients with Acquired LQTS, 123 I
      MIBG tomoscintigraphy demonstrated a decrease in the sympathetic myocardial
      innervation. Time--frequency analysis using wavelet transform, demonstrated an
      abnormal frequency content within the QRS complexes, in the patients with
      Acquired LQTS, similar to that found in Congenital LQTS patients. Molecular
      screening in 16 consecutive patients, identified one patient with a missense
      mutation on HERG, one of the LQTS genes. Expression of the mutated HERG protein
      led to altered K(+) channel function. CONCLUSION: Our results suggest that
      Acquired and Congenital Long QT Syndromes have some common features. They allow
      the mechanism of the clinical heterogeneity, found in both syndromes, to be
      understood. Further multi-facet approaches are needed to decipher the complex
      interplay between the main determinants of these arrhythmogenic diseases.

PMID- 11334844
TI  - Sudden cardiac death in young people with apparently normal heart.
AB  - OBJECTIVE: The aim of the present study was to assess the prevalence of subtle
      morphologic substrates, clinically unrecognizable, underlying sudden cardiac
      death (SCD) in young people with apparently normal heart. METHODS: In the time
      interval 1979--1998, 273 consecutive cases of SCD in young people (< or =35
      years) which occurred in the Veneto Region of Italy were prospectively studied.
      Following exclusion of extracardiac causes of sudden death, the heart was
      examined according to a detailed morphologic protocol consisting of macroscopic
      and histologic examination, including study of the specialized conduction system
      by serial sections. RESULTS: At macroscopic examination, 197 SCD victims (72%)
      had an overt underlying structural heart disease such as cardiomyopathy in 56,
      obstructive coronary atherosclerosis in 54, valve disease in 32, non
      atherosclerotic coronary artery disease in 28, aortic rupture in 13,
      postoperative congenital heart disease in five, and other disease in nine. The
      remaining 76 cases (28%) (50 males and 26 females, aged 4-35 years, mean 23+/-5
      years) had a macroscopically normal heart. A total of 28 of them (37%) had
      experienced one or more of the following prodroma: syncope, palpitations or both
      in 20, ECG abnormalities in 18 and arrhythmias in ten. In 79% of them, histologic
      examination disclosed concealed pathologic substrates consisting of focal
      myocarditis in 27 cases, regional arrhythmogenic right ventricular
      cardiomyopathy, mostly localized to RV outflow tract, in nine, and conduction
      system abnormalities in 24 (leading to ventricular preexcitation in 18 and heart
      block in six). In 16 hearts (6%) there was no evidence of structural heart
      disease even after histologic study. CONCLUSION: Macroscopic heart features were
      normal in nearly one-third of young SCD victims. In 79% of them, however,
      histologic study unmasked concealed pathologic substrates such as focal
      myocarditis or cardiomyopathy and conduction system diseases. A total of 16
      victims (6%) had no evidence of structural heart disease and the mechanism of
      their SCD remained unexplained.

PMID- 11334845
TI  - Sympathetic nerve sprouting, electrical remodeling and the mechanisms of sudden
      cardiac death.
AB  - The purpose of this article is to review the nerve sprouting hypothesis of sudden
      cardiac death. It is known that sympathetic stimulation is important in the
      generation of sudden cardiac death. For example, there is a diurnal variation of
      sudden death rate in patients with myocardial infarction. Beta blockers, or drugs
      with beta blocking effects, are known to prevent sudden cardiac death. It was
      unclear if the cardiac nerves in the heart play only a passive role in the
      mechanisms of sudden death. To determine if nerve sprouting and neural remodeling
      occur after myocardial infarction, we performed immunocytochemical studies of
      cardiac nerves in explanted native hearts of transplant recipients. We found that
      there was a positive correlation between nerve density and a clinical history of
      ventricular arrhythmia. Encouraged by these results, we performed a study in dogs
      to determine whether or not nerve growth factor (NGF) infusion to the left
      stellate ganglion can facilitate the development of ventricular tachycardia (VT),
      ventricular fibrillation (VF), and sudden cardiac death (SCD). The results showed
      that augmented myocardial sympathetic nerve sprouting through NGF infusion plus
      atrioventricular (AV) block and MI result in a 44% incidence (four of nine dogs)
      of SCD and a high incidence of VT in the chronic phase of MI. In contrast, none
      of the six dogs (with AV block and MI) without NGF infusion died suddenly or had
      frequent VT episodes. Based on these findings, we propose the nerve sprouting
      hypothesis of ventricular arrhythmia and SCD. The hypothesis states that MI
      results in nerve injury, followed by sympathetic nerve sprouting and regional
      (heterogeneous) myocardial hyperinnervation. The coupling between augmented
      sympathetic nerve sprouting with electrically remodeled myocardium results in VT,
      VF and SCD. Modification of nerve sprouting after MI may provide a novel
      opportunity for arrhythmia control.

PMID- 11334846
TI  - Use of A-192621 to provide evidence for involvement of endothelin ET(B)-receptors
      in endothelin-1-mediated cardiomyocyte hypertrophy.
AB  - Increased plasma levels of endothelin-1 correlate with the severity of left
      ventricular hypertrophy in vivo. The aim of the study was to determine the
      relative contribution of stimulation of endothelin ET(A) and endothelin ET(B)
      receptors, and the associated activation of protein kinase C, to the hypertrophic
      response initiated by endothelin-1 in adult rat ventricular cardiomyocytes
      maintained in culture (24 h). Endothelin-1 (10(-7) M) increased the total mass of
      protein and the incorporation of [14C] phenylalanine into protein to 26% and 25%
      greater (P<0.05) than respective basal values. The total content of RNA and the
      incorporation of 2-[14C] uridine into RNA were increased by 23% and 21%,
      respectively, by endothelin-1 (10(-8) M). Actinomycin D (5x10(-6) M), an
      inhibitor of transcription, abolished the incorporation of [14C] phenylalanine
      and the increased protein mass elicited by endothelin-1 (10(-8) M). The selective
      agonists at the endothelin ET(B) receptor, sarafotoxin 6c (10(-7) M) and
      endothelin-3 (10(-7) M), increased the incorporation of [14C] phenylalanine to
      13% and 13% greater than respective basal values. The incorporation of
      [14C]phenylalanine in response to endothelin-1 (10(-7) M) was reduced by 50%
      (P<0.05) by the selective antagonist at endothelin ET(A) receptors, ABT-627 (10(
      9) M), while the response to sarafotoxin 6c was not attenuated. The selective
      antagonist at endothelin ET(B) receptors, A192621 (10(-10) M), abolished the
      response to sarafotoxin 6c (10(-7) M) and attenuated the response to endothelin-1
      (10(-7) M) by 43% (P<0.05). The selective inhibitor of protein kinase C,
      bisindolylmaleimide (5x10(-6) M) attenuated the response to sarafotoxin 6c (10(
      7) M) by 78% and that to endothelin-1 (10(-7) M), elicited in the presence of
      A192621 (10(-10) M), by 52%. In conclusion, these data implicate endothelin ET(B)
      receptors, in addition to endothelin ET(A) receptors, in endothelin-1-mediated
      cardiomyocyte hypertrophy and provide evidence for the involvement of protein
      kinase C, at least in part, in the hypertrophic signalling pathways associated
      with activation of each receptor subpopulation.

PMID- 11334847
TI  - Uptake mechanism of valproic acid in human placental choriocarcinoma cell line
      (BeWo).
AB  - Valproic acid is an anticonvulsant widely used for the treatment of epilepsy.
      However, valproic acid is known to show fetal toxicity, including teratogenicity.
      In the present study, to elucidate the mechanisms of valproic acid transport
      across the blood-placental barrier, we carried out transcellular transport and
      uptake experiments with human placental choriocarcinoma epithelial cells (BeWo
      cells) in culture. The permeability coefficient of [3H]valproic acid in BeWo
      cells for the apical-to-basolateral flux was greater than that for the opposite
      flux, suggesting a higher unidirectional transport in the fetal direction. The
      uptake of [3H]valproic acid from the apical side was temperature-dependent and
      enhanced under acidic pH. In the presence of 50 microM carbonyl cyanide p
      trifluoromethoxylhydrazone, the uptake of [3H]valproic acid was significantly
      reduced. A metabolic inhibitor, 10 mM sodium azide, also significantly reduced
      the uptake of [3H]valproic acid. Therefore, valproic acid is actively transported
      in a pH-dependent manner on the brush-border membrane of BeWo cells. Kinetic
      analysis of valproic acid uptake revealed the involvement of a non-saturable
      component and a saturable component. The Michaelis constant for the saturable
      transport (K(t)) was smaller under acidic pH, suggesting a proton-linked active
      transport mechanism for valproic acid in BeWo cells. In the inhibitory
      experiments, some short-chain fatty acids, such as acetic acid, lactic acid,
      propanoic acid and butyric acid, and medium-chain fatty acids, such as hexanoic
      acid and octanoic acid, inhibited the uptake of [3H]valproic acid. The uptake of
      [3H]valproic acid was also significantly decreased in the presence of 4,4'
      diisothiocyanatostilbene-2,2'-disulfonic acid, salicylic acid and furosemide,
      which are well-known inhibitors of the anion exchange system. Moreover, p
      aminohippuric acid significantly reduced the uptake of [3H]valproic acid. These
      results suggest that an active transport mechanism for valproic acid exists on
      the brush-border membrane of placental trophoblast cells and operates in a proton
      linked manner.

PMID- 11334848
TI  - Pharmacological characterization of homobaclofen on wild type and mutant
      GABA(B)1b receptors coexpressed with the GABA(B)2 receptor.
AB  - Homobaclofen (5-amino-3-(4-chlorophenyl) pentanoic acid) is a homologue of the
      classical GABA(B) receptor agonist baclofen. In a recent study, the two
      enantiomers of this compound were tested in a GABA(B) receptor selective
      [3H]gamma-aminobutyric acid ([3H]GABA) binding assay using rat brain homogenate
      and in an assay of electrically induced contractions of guinea pig ileum. The
      results from the two tissues did, however, not correlate very well, and in order
      to further investigate these discrepancies, we have pharmacologically
      characterized these enantiomers on recombinant wild type and mutant rat GABA(B)1b
      receptors coexpressed with rat GABA(B)2 receptors. The results from this study
      correlate nicely with the binding data from rat brain. (R)-Homobaclofen was shown
      to act like (R)-baclofen albeit with 20-fold less potency, and (S)-homobaclofen
      was inactive on the receptor. The discrepancies between the data obtained in this
      study and those from the guinea pig ileum model could be ascribed to differences
      in amino acid sequence or receptor splicing of GABA(B) receptors between the two
      species. Another explanation for the observation is the possible existence of a
      novel yet uncloned GABA(B) receptor in guinea pig ileum.

PMID- 11334849
TI  - Cell death with atypical features induced by the novel antitumoral drug CHS 828,
      in human U-937 GTB cells.
AB  - N-(6-(4-chlorophenoxy)hexyl)-N'-cyano-N"-4-pyridylguanidine (CHS 828), with
      promising antitumoral effects in vitro and in vivo, is currently in clinical
      Phase I and II studies. Its exact mechanism of action is unclear, but previous
      studies indicate that CHS 828 induces a controlled, delayed mode of cell death.
      The characteristics of the cell death process were investigated in vitro in the
      apoptosis-prone cell line U-937 GTB. Mitochondria showed hyperpolarization at 24
      to 32 h and a subsequent late disruption of mitochondria membrane potential
      (Deltapsi(m)). Between 44 and 72 h of CHS 828 exposure, there was an increasing
      frequency of terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end
      labeling (TUNEL) positive cells indicative of apoptosis, but caspase-3 was only
      modestly increased and caspases-8 and -9 showed no activation upon CHS 828
      exposure. Furthermore, the morphology of exposed cells did not conform to
      classical apoptosis, and viability and morphology were unaffected by inhibition
      of caspases. Thus, CHS 828 induces several unexpected features in this system,
      suggesting a potentially novel mechanism of action.

PMID- 11334850
TI  - M100907, a selective 5-HT(2A) receptor antagonist, attenuates phencyclidine
      induced Fos expression in discrete regions of rat brain.
AB  - 5-HT and dopamine receptor antagonists have become widely used as atypical
      antipsychotics. Although 5-HT(2A) receptor antagonistic activity is thought to
      contribute to the atypical aspects of these agents, the precise mechanism remains
      unknown. M100907 (R(+)-alpha(2,3-dimethoxyphenyl)-1-[2(4-fluorophenyl)ethyl)]-4
      piperidine -methanol), a selective 5-HT(2A) receptor antagonist, is reported to
      attenuate phencyclidine (PCP)-induced locomotion in rodents. For the purpose of
      identifying regions in which M100907 exerts its effect, we investigated the
      effects of M100907 on PCP-induced Fos expression in rat brain. PCP (5 mg/kg,
      subcutaneously, s.c.) induced Fos expression in the cingulate cortex area 3, the
      agranular insular cortex, the piriform cortex, the nucleus accumbens, the
      anterior paraventricular thalamic nucleus and the ventral lateral septal nucleus.
      Pretreatment with M100907 (0.5 mg/kg, s.c.) attenuated Fos expression induced by
      PCP in the nucleus accumbens core, the shell, the agranular insular cortex and
      the piriform cortex. M100907 did not induce Fos expression in any of the regions
      investigated including the dorsolateral caudate/putamen when given alone. These
      results indicate that 5-HT(2A) receptor antagonism attenuates Fos expression in a
      regionally specific manner in rat brain in the PCP model of psychosis.

PMID- 11334851
TI  - A61603-induced vasoconstriction in porcine carotid vasculature: involvement of a
      non-adrenergic mechanism.
AB  - It has recently been shown that the pharmacological profile of alpha(1)
      adrenoceptors mediating constriction of porcine carotid arteriovenous anastomoses
      resembles that of alpha(1A)- and alpha(1B)-adrenoceptor subtypes. In an attempt
      to verify the involvement of alpha(1A)-adrenoceptors, we used the potent
      alpha(1A)-adrenoceptor agonist N-[5-(4,5-dihydro-1H-imidazol-2yl)-2-hydroxy
      5,6,7,8-tetrahydro-naphthalen-1-yl]methane sulphonamide (A61603) and found that
      intracarotid (i.c.) administration of A61603 (0.3-10 microg kg(-1)) dose
      dependently decreased porcine carotid blood flow and vascular conductance. This
      decrease was exclusively due to a constriction of carotid arteriovenous
      anastomoses; the capillary blood flow and conductance remained unchanged.
      Surprisingly, the responses to A61603 were little modified by prior i.v.
      treatment with 5-methylurapidil (1000 microg kg(-1)), prazosin (100 microg kg(
      1)) or a combination of prazosin and rauwolscine (100 and 300 microg kg(-1),
      respectively). The 5-HT(1B/1D) receptor antagonist 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 monohydrate (GR127935; 500 microg kg(-1)) and
      ketanserin (500 microg kg(-1)) also failed to modify carotid vascular responses
      to A61603, but, interestingly, methiothepin (3000 microg kg(-1)) proved to be an
      effective antagonist. Taken together, the present results show that A61603 is a
      relatively poor agonist at the alpha(1A)-adrenoceptor in anaesthetised pigs and
      that the carotid vasoconstriction produced by A61603 is mediated by a novel non
      adrenergic mechanism.

PMID- 11334852
TI  - Evidence for a K(ATP) ion channel link in the inhibition of hypercapnic dilation
      of pial arterioles by 7-nitroindazole and tetrodotoxin.
AB  - 7-Nitroindazole, an inhibitor of neuronal nitric oxide synthase, reportedly
      inhibits hypercapnic dilation, but tetrodotoxin, an inhibitor of neuronal
      transmission, reportedly does not. Thus, evidence does not uniformly support the
      hypothesis of a neurogenic link to the hypercapnic response. Others suggest the
      hypercapnic response is mediated by a K(ATP) ion channel. In the following
      studies, we observed that topically administered tetrodotoxin inhibited dilations
      produced by hypercapnia. In addition, topical tetrodotoxin and either topical or
      intraperitoneal 7-nitroindazole, inhibited dilations produced by the K(ATP)
      channel openers, cromakalim and pinacidil. Inhibition of hypercapnic dilation and
      inhibition of dilation by the openers of the K(ATP) channel was immediately
      reversed by either L-lysine or L-arginine, amino acids previously shown to
      facilitate opening of the channel. The data strongly supports the previous
      conclusion that there is a K(ATP) ion channel link in the response of pial
      arterioles to hypercapnia. The location of the channel is not established by
      these data, nor is it known whether the action of tetrodotoxin on the channel was
      direct or indirect.

PMID- 11334853
TI  - Thromboxane A(2) synthase inhibitor enhanced antithrombotic efficacy of GPIIb
      IIIa receptor antagonist without increasing bleeding.
AB  - The advantage of platelet integrin GPIIb-IIIa receptor antagonists in the
      prevention of thrombotic occlusion was clearly proven in patients who underwent
      interventional treatment of the coronary artery, but its value in cerebral
      ischemia is still under investigation. The expectation of intracranial hemorrhage
      on strong inhibition of platelet function restricts its application in cerebral
      ischemia. To minimize bleeding while keeping antithrombotic activity, we have
      tried to find an appropriate approach using a combination of platelet integrin
      GPIIb-IIIa receptor antagonist and some other antithrombotic agents. The time to
      thrombotic occlusion was measured using a photothrombotic occlusion model of
      guinea pig middle cerebral artery. A platelet integrin GPIIb-IIIa receptor
      antagonist, ME3277 (sodium hydrogen [4-[(4,5,6,7-tetrahydrothieno [3,2-c] pyridin
      2-yl) carbonylamino] acetyl-o-phenylene] dioxydiacetate), delayed occlusion time
      from 7.3 min in vehicle to 15.0, 20.6 and 25.9 min (P<0.05) at 0.1, 0.3 and 1
      mg/kg, respectively. ME3277 profoundly inhibited ex vivo platelet aggregation and
      the highest dose of ME3277 prolonged (3.5 folds, P<0.01) the bleeding time
      measured in the hind paw. A thromboxane A(2) synthase inhibitor, sodium ozagrel,
      significantly delayed occlusion time to 19.5 min at 30 mg/kg (P<0.05) while it
      did not affect bleeding time or platelet aggregation. ME3277 (0.1 mg/kg) in
      combination with 10 mg/kg sodium ozagrel synergistically delayed occlusion time
      (sodium ozagrel alone; 7.9 min, combination; 26.1 min, P<0.05 vs. ME3277 alone).
      Sodium ozagrel did not affect ex vivo platelet aggregation or bleeding time when
      combined with 0.1 mg/kg of ME3277. This synergy was cancelled by combination with
      30 mg/kg aspirin (14.7 min). A thromboxane A(2) receptor antagonist, vapiprost
      (0.1 mg/kg), did not enhance the antithrombotic efficacy of ME3277. These results
      imply that local prostacyclin production enhances the in vivo antithrombotic
      effect of the platelet integrin GPIIb-IIIa receptor antagonist. Therefore, the
      thromboxane A(2) synthase inhibitor allowed a reduction in the dose level of the
      platelet integrin GPIIb-IIIa receptor antagonist for cerebral thrombosis, which
      resulted in a reduced risk of bleeding.

PMID- 11334854
TI  - Neurovascular interactions between aldose reductase and angiotensin-converting
      enzyme inhibition in diabetic rats.
AB  - Increased polyol pathway flux has been linked to nerve complications in diabetic
      rats, which are attenuated by aldose reductase inhibitors, defective nitric oxide
      mediated vasodilation being a particular target. Diabetes also elevates the
      endothelial angiotensin system, increasing vasa nervorum vasoconstriction. The
      aim was to assess whether promotion of vasodilation by treatment with the aldose
      reductase inhibitor, ZD5522 (3',5'-dimethyl-4'-nitromethylsulphonyl-2-(2
      tolyl)acetanilide), coupled with reduced vasoconstriction using the angiotensin
      converting enzyme inhibitor, lisinopril, interacted positively to improve
      neurovascular function. After 8 weeks of streptozotocin-induced diabetes, sciatic
      nerve blood flow and motor conduction velocity were 51% and 21% reduced,
      respectively. Two weeks of lisinopril treatment dose-dependently corrected the
      conduction deficit (ED(50) approximately 0.9 mg kg(-1)). Low-dose lisinopril (0.3
      mg kg(-1)) or ZD5522 (0.25 mg kg(-1)) had modest corrective (10-20%) effects on
      nerve conduction and perfusion. However, when combined, blood flow and conduction
      velocity reached the nondiabetic range. The ZD5522 dose used gave a approximately
      45% nerve sorbitol reduction but had no significant effect on fructose content;
      lisinopril co-treatment did not alter ZD5522 action on polyols. Thus, there was a
      marked neurovascular synergistic interaction between angiotensin-converting
      enzyme and aldose reductase inhibition in diabetic rats. This points to a
      potential therapeutic benefit, which requires evaluation in clinical trials.

PMID- 11334855
TI  - Action of glucocorticoids to antagonise cisplatin-induced acute and delayed
      emesis in the ferret.
AB  - Cisplatin 5 mg/kg, i.p. induced an acute (day 1) and delayed (days 2 and 3)
      emetic response in the ferret that was used to investigate the potential anti
      emetic activity of several glucocorticoids. Betamethasone (0.3-3 mg/kg, i.p.)
      reduced the emesis occurring during the initial 0-24-h period by 71.1-99.5%
      (P<0.05). The action of methylprednisolone (1.0-10.0 mg/kg, i.p.) and
      hydrocortisone (1.0-30.0 mg/kg, i.p.) could not be assessed because the controls
      exhibited weak emetic responses and dexamethasone produced a non-significant
      64.0% reduction at 0.3 mg/kg (P>0.05). However, all glucocorticoids dose
      dependently reduced retching+vomiting during the subsequent 24-56-h period. The
      rank order of anti-emetic potency was betamethasone (ID(80)<0.3
      mg/kg)>/=dexamethasone (ID(80)=0.32 mg/kg)>methylprednisolone (ID(80)=0.66
      mg/kg)&z.Gt;hydrocortisone (ID(80)>30 mg/kg). Dexamethasone was ineffective to
      antagonise the retching+vomiting response during the 24-56-h period when the
      administration was delayed until 24 h post-cisplatin injection. None of the
      glucocorticoids reduced the retching+vomiting response occurring during the 56-72
      h period. In conclusion, the rank order of anti-emetic potency suggests that
      inflammation, or mediators of inflammation, contribute to the retching+vomiting
      response induced by cisplatin.

PMID- 11334856
TI  - Cyclooxygenase-2 protein and prostaglandin E(2) production are up-regulated in a
      rat bladder inflammation model.
AB  - Cyclooxygenase-1 and cyclooxygenase-2 mRNAs and proteins and prostaglandin E(2)
      production are evaluated in a rat model of inflammation in which Escherichia coli
      lipopolysaccharide is intraperitoneally injected or intravesically instilled into
      the bladder. While cyclooxygenase-1 mRNA and protein and cyclooxygenase-2 mRNA do
      not change in bladders treated with lipopolysaccharide, cyclooxygenase-2 protein
      is elevated in bladders from rats intravesically instilled with
      lipopolysaccharide or phosphate buffered saline (PBS) or intraperitoneally
      injected with lipopolysaccharide. Urinary prostaglandin E(2) levels and
      prostaglandin E(2) synthesis in bladder particulates are elevated by intravesical
      instillation and intraperitoneal injection of lipopolysaccharide. The nitric
      oxide donor, S-nitroso-N-acetyl-D,L-penicillamine, increases prostaglandin E(2)
      synthesis in bladders from lipopolysaccharide intravesically instilled and
      intraperitoneally injected rats. Lipopolysaccharide increases prostaglandin E(2)
      synthesis by increasing cyclooxygenase-2 protein levels in rat bladder and
      prostaglandin E(2) synthesis may be further elevated by increases in nitric oxide
      caused by an up-regulation of inducible nitric oxide synthase (iNOS).

PMID- 11334857
TI  - In vitro metabolism of gestodene in target organs: formation of A-ring reduced
      derivatives with oestrogenic activity.
AB  - Gestodene (13beta-ethyl-17alpha-ethynyl-17beta-hydroxy-4,5-gonadien-3-one), the
      most potent progestin ever synthesized, stimulates breast cancer cell growth
      through an oestrogen receptor-mediated mechanism, and its use in hormonal
      contraception has been associated with side effects attributable to oestrogenic
      actions. These observations have remained controversial, since gestodene does not
      bind to the oestrogen receptor or exert oestrogen-like activities. Recently, we
      have demonstrated that non-phenolic gestodene derivatives interact with oestrogen
      receptors and induce oestrogenic effects in cell expression systems. To assess
      whether gestodene is biotransformed to metabolites with intrinsic oestrogenic
      potency, [3H]- and [14C]-labelled gestodene were incubated in vitro with rat
      anterior pituitary, hypothalamus and ventral prostate homogenates under different
      experimental conditions. The most remarkable finding was the isolation and
      identification of 3beta,5alpha-tetrahydrogestodene and 3alpha,5alpha
      tetrahydrogestodene as metabolic conversion products of gestodene, presumably
      with 5alpha-dihydrogestodene as intermediate. The overall results seem to
      indicate that the weak oestrogenic effects attributable to gestodene could be
      mediated by its tetrahydro metabolites.

PMID- 11334858
TI  - Involvement of K(+)-Cl(-)-cotransport in the apoptosis induced by N
      ethylmaleimide in HepG2 human hepatoblastoma cells.
AB  - The role of K(+)-Cl(-)-cotransport in apoptosis in human cancer cells was
      investigated. N-Ethylmaleimide, a K(+)-Cl(-)-cotransport activator, induced
      apoptosis in a dose-dependent manner in HepG2 human hepatoblastoma cells. N
      Ethylmaleimide induced Cl(-)-dependent K(+) efflux, indicating that K(+)-Cl(-)
      cotransport is functionally present in HepG2 cells. Calyculin-A and genistein,
      inhibitors of K(+)-Cl(-)-cotransport, significantly prevented both K(+)-Cl(-)
      cotransport activation and apoptosis induced by N-ethylmaleimide. These results
      demonstrate, for the first time, a novel role for K(+)-Cl(-)-cotransport in
      apoptosis in human hepatoma cells. These results further suggest that K(+)-Cl(-)
      cotransport may be a valuable target for therapeutic interventions for human
      hepatoma.

PMID- 11334859
TI  - Effects of azelastine on contractility, action potentials and L-type Ca(2+)
      current in guinea pig cardiac preparations.
AB  - Azelastine is used for symptomatic relief of allergic rhinitis and asthma
      bronchiale. In vitro studies in smooth muscle cells from guinea pig trachea and
      ileum demonstrate that the drug blocks L-type Ca(2+) current (I(Ca, L)). However,
      for safety reasons, it is important to know whether azelastine also affects
      cardiac I(Ca, L) in therapeutically relevant concentrations. We have therefore
      studied the effects of azelastine on I(Ca, L) in guinea pig ventricular myocytes
      using standard whole-cell patch-clamp technique. Force of contraction and action
      potentials from isolated papillary muscles of the same species were also
      investigated at physiological temperature (36 degrees C). Azelastine (30 microM)
      significantly reduced force of contraction, shortened action potential duration,
      and depressed maximum upstroke velocity. I(Ca, L) was elicited by 200-ms-long
      clamp steps from -100 to 0 mV (one pulse every 3 s). Azelastine blocked I(Ca, L)
      reversibly and concentration-dependently with an IC(50) of 20.2+/-1.3 microM and
      a Hill coefficient of 1.1. At 10 microM, azelastine shifted steady-state
      inactivation by 5 mV (n=7) to more negative potentials. The time course of I(Ca,
      L) inactivation could be described by a double exponential function. Azelastine
      (10 microM) significantly shortened the slow inactivation time constant (tau(s))
      from 54.2+/-2.8 ms under control conditions to 38.7+/-2.9 ms (n=16) in the
      presence of drug. Azelastine also reduced low-voltage-activated Ca(2+) currents
      with a similar IC(50) value (24 microM, at -35 mV). Since the therapeutic plasma
      concentrations are in the order of 10-100 nM, we conclude that azelastine does
      indeed affect also cardiac I(Ca, L), but the concentrations required are at least
      two orders of magnitude larger than those obtained during drug therapy.

PMID- 11334861
TI  - Expression of 74-kDa histidine decarboxylase protein in a macrophage-like cell
      line RAW 264.7 and inhibition by dexamethasone.
AB  - Stimulation of RAW 264.7 cells with the Ca(2+)-ATPase inhibitor thapsigargin
      increased histamine production. Immunoblot analyses revealed that thapsigargin
      increased the expression of 74-kDa histidine decarboxylase protein although rat
      mast cell line RBL-2H3 cells express both 74- and 53-kDa histidine decarboxylase
      proteins. The inhibition of histamine production by the mitogen-activated protein
      kinase-extracellular signal-regulated kinase kinase (MEK) inhibitors PD98059 (2'
      amino-3'-methoxyflavone) and U0126 (1,4-diamino-2,3-dicyano-1,4-bis(2
      aminophenylthio)butadiene) and by the p38 mitogen-activated protein (MAP) kinase
      inhibitor SB203580 (4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H
      imidazole) was correlated with the inhibition of the expression of thapsigargin
      induced 74-kDa histidine decarboxylase protein. The synthetic glucocorticoid
      dexamethasone inhibited thapsigargin-induced histamine production and 74-kDa
      histidine decarboxylase protein expression. The thapsigargin-induced activation
      of p42/p44 MAP kinase and p38 MAP kinase was also inhibited by dexamethasone.
      These findings indicate that the induction of histamine production by
      thapsigargin in RAW 264.7 cells is due to the increased expression of 74-kDa
      histidine decarboxylase protein and that dexamethasone inhibits thapsigargin
      induced histidine decarboxylase protein expression and histamine production via
      inhibition of MAP kinase activation.

PMID- 11334862
TI  - Changes in [(3)H]glibenclamide binding to mouse forebrain membranes during
      morphine tolerance.
AB  - The characteristics of specific binding of the ATP-sensitive K(+) (K(ATP))
      channel blocker [3H]glibenclamide to forebrain membranes (P(2) fraction, 4
      degrees C) obtained from morphine-naive and -tolerant mice were evaluated.
      Morphine tolerance was induced by osmotic minipumps that released 45 mg/kg/day of
      morphine subcutaneously for 6 days. This treatment enhanced the antinociceptive
      ED(50) of morphine without changing its E(max). In morphine-naive animals, (1)
      both the association and the dissociation of [3H]glibenclamide were biphasic; (2)
      [3H]glibenclamide was displaced by other sulfonylureas (order of potency:
      glibenclamide>glipizide&z.Gt;tolbutamide) with pseudo-Hill coefficients lower
      than unity and biphasic Hofstee plots; and (3) Scatchard plots of saturation
      experiments were curvilinear, showed a Hill coefficient of 0.81+/-0.04 and
      suggested the presence of two binding sites with a K(D) of 0.13 and 3.17 nM and a
      B(max) of 12.30 and 84.47 fmol/mg protein, respectively. By contrast, in
      membranes obtained from morphine-tolerant animals, (1) the Scatchard plots showed
      only one population of binding sites with a K(D) of 0.87 nM and a B(max) of 77.99
      fmol/mg protein, and the Hill coefficient was very close to unity (0.96+/-0.1);
      (2) competition experiments (using glibenclamide as displacer) showed a pseudo
      Hill coefficient of 0.99+/-0.04; and (3) dissociation experiments showed only one
      phase of dissociation. These results suggest that [3H]glibenclamide binds to two
      different sites in membranes obtained from morphine-naive animals, but to only
      one site in morphine-tolerant animals. Consequently, it seems that morphine
      tolerance in mice involves adaptive changes in K(ATP) channels.

PMID- 11334860
TI  - 5-Lipoxygenase is required for proliferation of immature cerebellar granule
      neurons in vitro.
AB  - Primary cultures of rat cerebellar granule neurons express 5-lipoxygenase, an
      enzyme from the inflammatory pathway of arachidonic acid. Outside the central
      nervous system (CNS) 5-lipoxygenase participates in cell proliferation. We
      hypothesized that 5-lipoxygenase is needed for proliferation of immature
      cerebellar granule neurons. Using cultures prepared from 7-day-old rat pups, we
      confirmed in vitro neurogenesis by immunocytolabeling with 2-bromo-5-deoxyuridine
      and beta-tubulin isotype III and quantified the rate of cell proliferation by
      assaying [3H]thymidine incorporation. We found that immature cerebellar granule
      neurons express large amounts of 5-lipoxygenase, and that treatment with a 5
      lipoxygenase antisense, to reduce expression of this gene, decreased
      significantly (by 60%) the content of 5-lipoxygenase protein and effectively
      reduced cell proliferation. [3H]thymidine incorporation was significantly reduced
      by each of the three 5-lipoxygenase inhibitors we tested: AA-861 [2-(12
      hydroxydodeca-5, 10-diynyl)-3,5,6-trimethyl-1,4-benzoquinone], MK-886
      (C(27)H(33)ClNO(2)S.Na), and L-655,238 [alpha-penyl-3-(2-quinolinylmethoxy)
      benzenemethanol]. Their anti-proliferative effect was reversible. We propose that
      neuronal expression of 5-lipoxygenase is crucial for neurogenesis in vitro, and
      possibly also in vivo.

PMID- 11334863
TI  - Cellular pharmacodynamics of the cytotoxic guanidino-containing drug CHS 828.
      Comparison with methylglyoxal-bis(guanylhydrazone).
AB  - N-(6-(4-chlorophenoxy)hexyl)-N'-cyano-N"-4-pyridylguanidine (CHS 828) is a new
      guanidino-containing compound with antitumoral activity both in vitro and in
      vivo. Its activity profile differs from those of standard cytotoxic drugs but the
      mechanism of action is not yet fully understood. CHS 828 is presently in early
      phase I and II clinical trials. In the present study, the pharmacodynamic effects
      at the cellular level of CHS 828 was compared to another compound containing two
      guanidino groups, methylglyoxal-bis(guanylhydrazone) (MGBG). MGBG is known to
      inhibit the synthesis of polyamines, which are important in, e.g., proliferation
      and macromolecular synthesis. The concentration-response relationship of CHS 828
      closely resembled that of MGBG and the drugs were similar with respect to
      inhibition of DNA and protein synthesis. On the other hand, CHS 828 induced a
      significant increase in cellular metabolism while MGBG did not. The cytotoxic
      effect of MGBG was reversed by the addition of exogenous polyamines, while that
      of CHS 828 was unaffected. Unlike MGBG, there was also no effect of CHS 828 on
      the levels of decarboxylating enzymes in the polyamine biosynthesis. In
      conclusion, CHS 828 does not appear to share any major mechanisms of action with
      the polyamine synthesis inhibitor MGBG. Further studies will be required to
      define the exact mechanism of action of CHS 828.

PMID- 11334864
TI  - Topographical assessment and pharmacological characterization of orofacial
      movements in mice: dopamine D(1)-like vs. D(2)-like receptor regulation.
AB  - A novel procedure for the assessment of orofacial movement topographies in mice
      was used to study, for the first time, the individual and interactive involvement
      of dopamine D(1)-like vs. D(2)-like receptors in their regulation. The dopamine
      D(1)-like receptor agonists A 68930 ([1R,3S]-1-aminomethyl-5,6-dihydroxy-3-phenyl
      isochroman) and SK&F 83959 (3-methyl-6-chloro-7,8-dihydroxy-1-[3-methyl-phenyl]
      2,3,4,5-tetrahydro-1H-3-benzazepine) each induced vertical jaw movements with
      tongue protrusions and incisor chattering. The dopamine D(1)-like receptor
      antagonists SCH 23390 ([R]-3-methyl-7-chloro-8-hydroxy-1-phenyl-2,3,4,5
      tetrahydro-1H-3-benzazepine) and BW 737C ([S]-6-chloro-1-[2,5-dimethoxy-4
      propylbenzyl]-7-hydroxy-2-methyl-1,2,3,4-tetrahydroisoquinoline) antagonised
      these responses, while the dopamine D(2)-like receptor antagonist YM 09151-2 (cis
      N-[1-benzyl-2-methyl-pyrrolidin-3-yl]-5-chloro-2-methoxy-4-methylaminobenzamide)
      attenuated those to SK&F 83959 and released horizontal jaw movements. These
      findings suggest some role for a dopamine D(1)-like receptor that is coupled to a
      transduction system other than/additional to adenylyl cyclase, and for dopamine
      D(1)-like:D(2)-like receptor interactions, in the regulation of individual
      orofacial movement topographies in the mouse. This methodology will allow the use
      of knockout mice to clarify the roles of individual dopamine receptor subtypes in
      their regulation.

PMID- 11334866
TI  - beta-Phenylethylamine modulates acetylcholine release in the rat striatum:
      involvement of a dopamine D(2) receptor mechanism.
AB  - We examined the effects of beta-phenylethylamine on striatal acetylcholine
      release in freely moving rats using in vivo microdialysis. beta-Phenylethylamine
      at 12.5 mg/kg, i.p. did not affect acetylcholine release in the striatum, whereas
      25 and 50 mg/kg, i.p. immediately induced an increase in acetylcholine release in
      the striatum at 15-45 min. This increase following intraperitoneal administration
      of beta-phenylethylamine (25 mg/kg) was not affected by locally applied SCH-23390
      (R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine,
      10 microM), a dopamine D(1) receptor antagonist, nor by raclopride (10 microM), a
      dopamine D(2) receptor antagonist. The increased release of acetylcholine induced
      by beta-phenylethylamine was suppressed by local infusion of tetrodotoxin (1
      microM). In contrast, the extracellular acetylcholine level in the striatum was
      significantly decreased by local application of beta-phenylethylamine (10 and 100
      microM) in the striatum via a microdialysis probe. The decrease was completely
      blocked by local co-application of raclopride (10 microM). The beta
      phenylethylamine-induced decrease in striatal acetylcholine release was not
      affected by co-perfusion with SCH-23390 (10 microM). These results indicate that
      systemic administration of beta-phenylethylamine increases acetylcholine release,
      whereas locally applied beta-phenylethylamine decreases striatal acetylcholine
      release in freely moving rats. Furthermore, the dopaminergic system, through the
      dopamine D(2) receptor, is involved in the locally applied beta-phenylethylamine
      induced decrease in acetylcholine in the striatum.

PMID- 11334865
TI  - Activation of 5-HT(1B/1D) receptors in the mesolimbic dopamine system increases
      dopamine release from the nucleus accumbens: a microdialysis study.
AB  - This study was designed to investigate the role of 5-hydroxytryptamine (5-HT)(1B)
      receptors located in the ventral tegmental area and nucleus accumbens in the
      modulation of accumbal dopaminergic transmission. The selective 5-HT(1B) receptor
      agonist CP 93129 [3-(1,2,5,6-tetrahydro-4-pyridyl)pyrrolo[3,2-b]pyrid-5-one] was
      administered into the ventral tegmental area or nucleus accumbens of freely
      moving Sprague-Dawley rats via retrograde microdialysis. The effects of intra
      accumbal and intra-tegmental CP 93129 on extracellular dopamine levels in the
      nucleus accumbens were measured using one- and dual-probe microdialysis,
      respectively. For dual-probe microdialysis, one probe was in the ventral
      tegmental area for drug administration and the other in the ipsilateral nucleus
      accumbens for dopamine measurement. The results show that infusion of CP 93129
      (2, 5 and 10 microM) into the nucleus accumbens increased local dopamine levels
      in a concentration-related manner. Infusion of CP 93129 (10 and 20 microM) into
      the ventral tegmental area also increased dopamine levels in the ipsilateral
      nucleus accumbens. The increased dopamine release in the nucleus accumbens
      produced by intra-accumbal or intra-tegmental CP 93129 was antagonized by co
      infusion of cyanopindolol (5 microM), a 5-HT(1B/1A) receptor antagonist, but not
      by WAY-100635 [N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-2-pyridinyl
      cyclohexanecarboxamide] (5 microM), a highly selective 5-HT(1A) receptor
      antagonist. In addition, augmentations of dopamine release in the nucleus
      accumbens induced by intra-accumbal CP 93129 were sensitive to Na(+) channel
      blockade with tetrodotoxin. These results are not in opposition to the concept
      that 5-HT(1B) receptors within the ventral tegmental area and nucleus accumbens
      are all involved in the modulation of dopamine release in the terminal area of
      the mesolimbic dopamine system.

PMID- 11334867
TI  - Effects of dopaminergic agents on carrageenan hyperalgesia after intrathecal
      administration to rats.
AB  - The present study explored the role of dopaminergic transmission in spinal cord
      in a model of carrageenan-induced inflammatory pain by examining the effects of
      selective agonists and antagonists of dopamine receptors. The results were as
      follows: (1) trans-(-)-4aR-4,4a,5,6,7,8,8a,9-octahydro-5-propyl-1H-pyrazolo[3,4
      g] quinoline hydrochloride (LY171555), a dopamine D(2) receptor agonist, produced
      anti-hyperalgesia (150 and 300 nmol) or hypoalgesia (300 nmol) in the inflamed
      hindpaws and non-inflamed hindpaws, respectively; spiperone hydrochloride (8-[4
      (4-fluorophenyl)-4-oxobutyl]-1-phenyl-1,3,8-triazaspiro[4,5]decan-4-one
      hydrochloride), a dopamine D(2) receptor antagonist, decreased the pain threshold
      of non-inflamed hindpaws (300 nmol). (2) (+/-)-SKF38393 hydrochloride ((+/-)-1
      phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol hydrochloride), a dopamine
      D(1) receptor agonist, had no effect on either hindpaw, even at a higher dose
      (300 nmol); R(+)-7-Chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3
      benzazepine hydrochloride (R(+)-SCH23390 hydrochloride), a dopamine D(1) receptor
      antagonist, induced anti-hyperalgesia in the inflamed hindpaws (300 nmol). The
      present results suggest that the dopaminergic system in the spinal cord is
      involved in the central modulation of inflammatory hyperalgesia, and that the
      different effects are probably induced by different receptors.

PMID- 11334868
TI  - Spinal delta-opioid receptors mediate suppression of systemic SNC80 on
      excitability of the flexor reflex in normal and inflamed rat.
AB  - Due to low central nervous system (CNS) bioavailability of delta-opioid peptides,
      little is known about the effect of systemic administration of delta-opioid
      receptor ligands. The present study examined the effect of non-peptidergic delta
      opioid receptor agonists, (+)-4-[(alphaR)-alpha-((2R,5R)-4-Allyl-2,5-dimethyl-1
      piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide (SNC80) and (-)dibenzoyl-L
      tartaric acid salt (SNC86), on the activity of alpha-motoneurons in decerebrate
      spinal rats. The flexor reflex was facilitated by C-afferent conditioning inputs,
      shown by a decrease in mechanical threshold and increase in touch- and pinch
      evoked responses. Systemic administration of SNC80 (10 micromol/kg) prevented and
      reversed the neuronal hyperactivity. We further examined the effect of this
      agonist on the hypersensitivity of the flexor reflex induced by intraplantar
      injection of Freund's adjuvant. SNC80 dose-dependently (1, 3, 5 and 10
      micromol/kg) increased the mechanical threshold and decreased touch-, pinch- and
      Abeta-afferent inputs-evoked responses. Similar effects were seen with SNC86 (5
      micromol/kg). Pretreatment with either naloxone (20 micromol/kg, i.p.) or
      (Cyclopropylmethyl)-6,7-dehydro-4,5alpha-epoxy-14beta-ethoxy-5beta-methylindolo
      [2',3':6',7']morphinan-3-ol hydrochloride (SH378; 5 micromol/kg, intraarterially
      (i.a.)), a novel selective delta-opioid receptor antagonist, completely abolished
      the anti-hypersensitivity effect of SNC80. The effect of SNC80 remained following
      intrathecal administration of mu-opioid receptor antagonist D-Phe-Cys-Tyr-D-Trp
      Orn-Thr-Pen-Thr-NH(2) (CTOP; 1.5 nmol). These results indicate that systemic
      injection of SNC80 exerted antihypersensitivity in models of both acute and tonic
      nociception and these effects are mediated mainly through a spinal delta-opioid
      mechanism.

PMID- 11334869
TI  - Late preconditioning in rat retina: involvement of adenosine and ATP-sensitive
      K(+) channel.
AB  - To determine whether stimulation of adenosine receptors and opening of ATP
      sensitive K(+) channels were involved in the protective effect of late
      preconditioning in the rat retina, rats were subjected to 60 min of retinal
      ischemia, and ischemic preconditioning was achieved by applying 5 min of ischemia
      24 h before 60 min of ischemia. In non-preconditioned rats, cell loss in the
      ganglion cell layer and thinning of the inner plexiform and inner nuclear layer
      were observed 7 days after 60 min of ischemia. Ischemic preconditioning
      completely prevented the retinal tissue damage and 8-phenyltheophylline or 5
      hydroxydecanoate reduced the protective effect of ischemic preconditioning.
      Therefore, stimulation of adenosine receptors and opening of ATP-sensitive K(+)
      channels might be involved in the mechanism of histological protection by late
      preconditioning in the retina.

PMID- 11334870
TI  - Pharmacology of H 394/84, a dihydropyridine neuropeptide Y Y(1) receptor
      antagonist, in vivo.
AB  - The object of the present paper was to investigate the in vivo pharmacological
      profile of the dihydropyridine neuropeptide Y Y(1) receptor antagonist 1,4
      Dihydro-4-[3-[[[[3-[spiro(indene-4,1'-piperidin-1
      yl)]propyl]amino]carbonyl]amino]phenyl]-2,6-dimethyl-3,5-pyridine dicarboxylic
      acid, dimethylester (H 394/84). The renal vasoconstrictor response to
      neuropeptide Y in anaesthetized rats was dose-dependently antagonized by H 394/84
      (ID(50) value=41+/-4 nmol/kg/min), whereas the renal vascular responses to
      noradrenaline and angiotensin II were only slightly affected by H 394/84 (500
      nmol/kg/min). In pigs pretreated with reserpine and transection of sympathetic
      nerves (depleted of noradrenaline), H 394/84 dose-dependently antagonized renal
      and femoral vasoconstrictor responses evoked by sympathetic nerve activation
      (neuronally released neuropeptide Y) and exogenous neuropeptide Y. Significant
      inhibition was seen already at 1.0 nmol/kg/min, when plasma levels of the
      antagonist reached 29+/-4 nM. Around 70% of the antagonism remained 90 min after
      H 394/84 was given. The disposition of H 394/84 fits a biexponential model with
      initial and terminal half-lives of 2.6 and 48 min, respectively. H 394/84 (100
      nmol/kg/min) did not inhibit vascular responses to neuropeptide Y Y(2) receptor-,
      alpha-adrenoceptor- or purinoceptor-activation in the pig in vivo. It is
      concluded that H 394/84 is a potent neuropeptide Y Y(1) receptor antagonist with
      rather long duration of action in vivo. The selectivity and specificity in vivo
      is more than 100-fold, and H 394/84 antagonizes vascular responses to exogenous
      and endogenous, neuronally released, neuropeptide Y with similar potency.

PMID- 11334871
TI  - Ranolazine, a partial fatty acid oxidation inhibitor, reduces myocardial infarct
      size and cardiac troponin T release in the rat.
AB  - Ranolazine reduces cellular acetyl-CoA content via inhibition of fatty acid beta
      oxidation and activates pyruvate dehydrogenase. This metabolic switch increases
      ATP production per mole of oxygen consumed, reduces the rise in lactic acid and
      acidosis, and maintains myocardial function under conditions of reduced
      myocardial oxygen delivery. It is still unclear whether ranolazine causes a
      reduction of (i) infarct size and (ii) cardiac troponin T release, in a male
      Wistar rat model of left anterior descending coronary artery occlusion (25 min)
      and reperfusion (2 h). Rats were subjected to saline infusion (n=12) or
      ranolazine (bolus injection: 10 mg/kg plus infusion: 9.6 mg/kg/h, n=12), 30 min
      prior to left anterior descending coronary artery occlusion-reperfusion,
      respectively. Ranolazine caused a significant reduction in myocardial infarct
      size of approximately 33% compared to saline control (P<0.05). In addition,
      infusion of ranolazine significantly attenuated the release of cardiac troponin T
      into the plasma from 65+/-14 (controls) to 12+/-2 ng/ml. This study demonstrates
      for the first time that ranolazine significantly reduces (i) infarct size and
      (ii) cardiac troponin T release in rats subjected to left anterior descending
      coronary artery occlusion-reperfusion.

PMID- 11334872
TI  - SQ22536 and W-7 inhibit forskolin-induced cAMP elevation but not relaxation in
      newborn ovine pulmonary veins.
AB  - The role of cAMP in forskolin-induced relaxation was studied in isolated
      pulmonary veins of newborn lambs (7-12 days). In vessels preconstricted with
      endothelin-1, forskolin at concentrations < or =10(-7) M had no effect on cAMP
      content and adenylyl cyclase activity but caused up to 50% relaxation. At higher
      concentrations, forskolin markedly elevated cAMP content and adenylyl cyclase
      activity and caused a further relaxation. SQ22536 [9-(tetrahydro-2-furanyl)-9H
      purin-6-amine; an adenylyl cyclase inhibitor] and W-7 [N-(6-aminohexyl)-5-chloro
      1-naphthalensulfonamide; a calmodulin-dependent adenylyl cyclase inhibitor] had
      no significant effect on forskolin-induced relaxation but markedly inhibited the
      elevation of cAMP content and adenylyl cyclase activity caused by forskolin. Rp-8
      CPT-cAMPS [8-(4-chlorophenylthio)-adenosine-3',5'-cyclic monophosphorothioate; an
      inhibitor of cAMP-dependent protein kinases] and Rp-8-Br-PET-cGMPS (beta-phenyl
      1, N(2)-etheno-8-bromoguanosine-3',5'-cyclic monophosphorothioate; an inhibitor
      of cGMP-dependent protein kinases) attenuated the relaxation caused by a cAMP
      analog but not that caused by forskolin. These results suggest that cAMP may not
      play a major role in forskolin-induced relaxation of pulmonary veins of newborn
      lambs.

PMID- 11334874
TI  - Chronic cyclosporine administration induces renal P-glycoprotein in rats.
AB  - The effect of cyclosporine doses on renal P-glycoprotein expression was examined.
      Rats were given cyclosporine orally at 2, 10, 30 mg/kg/day or subcutaneously at
      1, 5, 15 mg/kg/day for 28 days with or without 14 days of additional vehicle
      dosing. Following cyclosporine dosing, renal function and P-glycoprotein
      expression were measured. Renal function was reduced in rats receiving oral
      cyclosporine and the highest subcutaneous dose, 15 mg/kg/day. Western blot
      analysis showed that cyclosporine administered orally at 10 and 30 mg/kg/day and
      subcutaneously at 15 mg/kg/day induced significantly renal P-glycoprotein
      expression. After discontinuation of cyclosporine, renal P-glycoprotein returned
      to pre-dosing levels in oral groups, whereas the return was incomplete in
      subcutaneous groups. These results indicate that cyclosporine induces renal P
      glycoprotein overexpression a dose-dependent manner.

PMID- 11334873
TI  - Cannabinoid inhibition of capsaicin-sensitive sensory neurotransmission in the
      rat mesenteric arterial bed.
AB  - The present study investigated whether cannabinoids can modulate
      neurotransmission mediated by capsaicin-sensitive sensory nerves in the rat
      isolated mesenteric arterial bed. Sensory neurogenic vasorelaxation mediated by
      electrical field stimulation was concentration-dependently attenuated by HU210
      (0.1-3 microM), a cannabinoid receptor agonist (from 62+/-8.3% to 6+/-2.1% at 3
      microM HU210). HU210 had no effect on relaxation to exogenous calcitonin gene
      related peptide, indicating a prejunctional action. The action of HU210 (1
      microM) was not affected by LY320135 (1 microM) or SR144528 (1 microM),
      cannabinoid CB(1) and CB(2) receptor antagonists, respectively. SR141716A (0.01-1
      microM), a cannabinoid CB(1) receptor antagonist, concentration-dependently
      augmented vasorelaxation to electrical field stimulation, but had no effect on
      responses to calcitonin gene-related peptide and capsaicin, indicating a possible
      role of endogenous cannabinoids in sensory neurotransmission in rat mesenteric
      arteries. These data show that the cannabinoid receptor agonist HU210 inhibits
      prejunctionally sensory neurotransmission in rat mesenteric arteries and that
      this action is independent of cannabinoid CB(1)- or CB(2)-like receptors.

PMID- 11334875
TI  - Inhibition of the expression of inducible nitric oxide synthase and
      cyclooxygenase-2 in macrophages by 7HQ derivatives: involvement of IkappaB-alpha
      stabilization.
AB  - Nitric oxide is an important biological mediator associated with multiple
      pathophysiological phenomena, such as platelet aggregation, vasodilation, septic
      shock, and autoimmune diseases. Prostaglandins, derived from cyclooxygenases,
      play prominent roles in homeostasis and inflammation. In this study, we
      characterized the effects of 7HQ derivatives (7-[(4-methylene-5-oxo-2-R-2
      tetrahydrofuranyl) methoxy]-3,4-dihydrocarbostyril, where R is methyl, phenyl, p
      fluorophenyl and p-phenylphenyl; 7HQ-1,-2,-3 and-4, respectively) in murine RAW
      264.7 cells, a macrophage-like cell line. Lipopolysaccharide, the active
      component of endotoxin, significantly induced the expression of inducible nitric
      oxide synthase and cyclooxygenase-2, leading to the accumulation of nitrite and
      prostaglandin E(2), respectively. These actions of lipopolysaccharide were
      inhibited by 7HQ derivatives; additionally, the inhibition of the expression,
      rather than the activity, of inducible nitric oxide synthase correlated well with
      that of nitric oxide formation. Western blotting and electrophoretic mobility
      shift assay results demonstrated that the 7HQ derivatives could effectively
      inhibit IkappaB-alpha degradation and nuclear factor kappaB (NF-kappaB)
      translocation. At higher concentrations, 7HQ derivatives also inhibited
      cyclooxygenase-2 enzyme activity. These results suggest that 7HQ derivatives
      exhibit inhibitory effects on lipopolysaccharide-induced nitric oxide production
      and expression of inducible nitric oxide synthase and cyclooxygenase-2 through
      inhibition of IkappaB-alpha degradation and NF-kappaB activation.

PMID- 11334876
TI  - Norbinaltorphimine, a selective kappa-opioid receptor antagonist, induces an itch
      associated response in mice.
AB  - We examined the possibility that scratching induced by norbinaltorphimine, a
      selective kappa-opioid receptor antagonist, is due to an itch sensation, using
      compound 48/80 as control pruritogenic agent. When norbinaltorphimine was
      injected s.c. into the rostral back, mice scratched the skin around the injection
      site with their hind paws. Although the intensity of the scratching could not be
      compared because the dose and injection route were different, the character and
      time course of the scratching behavior induced by compound 48/80 injected i.d.
      were similar to those with norbinaltorphimine. The scratching behavior induced by
      norbinaltorphimine was dose-dependently and significantly inhibited by
      pretreatment with chlorpheniramine. Compound 48/80-induced scratching was also
      dose-dependently and significantly inhibited by p.o. pretreatment with
      chlorpheniramine. The scratching behavior induced by norbinaltorphimine was dose
      dependently and significantly inhibited by pretreatment with U-50,488H (trans-(+/
      )-2-(3,4-dichlorophenyl)-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl] acetamide
      methansulfonate), a kappa-opioid receptor agonist. Unexpectedly, the scratching
      behavior induced by compound 48/80 was also dose-dependently and significantly
      reduced by pretreatment with U-50,488H. These results suggest that the injection
      of norbinaltorphimine into the rostral back of the mouse elicited scratching,
      which may be an itch-associated response. Furthermore, the scratching behavior
      produced by norbinaltorphimine may be due in part to the release of histamine
      followed by antagonism of kappa-opioid receptors.

PMID- 11334877
TI  - Methylenedioxymethamphetamine-induced suppression of interleukin-1beta and tumour
      necrosis factor-alpha is not mediated by serotonin.
AB  - The purpose of the present study was to examine the role of serotonin release in
      methylenedioxymethamphetamine (MDMA)-induced immunosuppression in rats. We
      examined the effect of pretreatment with the selective serotonin reuptake
      inhibitor paroxetine, and the tryptophan hydroxylase inhibitor para
      chlorophenylalanine on MDMA-induced suppression of interleukin-1beta and tumour
      necrosis factor (TNF)-alpha secretion following an in vivo lipopolysaccharide
      challenge. Although paroxetine blocked MDMA-induced serotonin depletion in the
      cortex and hypothalamus, it failed to alter the suppressive effect of MDMA on
      lipopolysaccharide-induced TNF-alpha secretion. Similarly, although para
      chlorophenylalanine caused a 90% depletion in cortical and hypothalamic serotonin
      content, it failed to alter the suppressive effect of MDMA on lipopolysaccharide
      induced interleukin-1beta or TNF-alpha secretion. In conclusion, although MDMA is
      a potent releaser of serotonin, the suppressive effects of MDMA on
      lipopolysaccharide-induced proinflammatory cytokine secretion cannot be
      attributed to its serotonin-releasing properties.

PMID- 11334878
TI  - Effect of 2',4'-dichlorobenzamil hydrochloride, a Na(+)-Ca(2+) exchange
      inhibitor, on human spermatozoa.
AB  - The present study is aimed to investigate the contact spermicidal efficacy of
      2',4'-dichlorobenzamil hydrochloride (DBZ), a Na(+)-Ca(2+) exchange inhibitor, on
      ejaculated human spermatozoa. The drug produced a dose- and time-dependent
      spermicidal action on human spermatozoa. A concentration of 4 mM produced total
      loss of sperm viability within 1 min of addition to total semen. On the other
      hand, a similar action on spermatozoa separated from semen was noted at 0.5 mM
      concentration. The loss of spermatozoal viability was accompanied with an
      increase in intracellular Ca(2+). Sperm revival testing with glucose suggested a
      spermicidal rather than a spermiostatic action.

PMID- 11334879
TI  - 12-Hydroxyeicosatetraenoic acid potentiates angiotensin II-induced pressor
      response in rats.
AB  - We studied whether 12-hydroxyeicosatetraenoic acid (HETE) affected the
      angiotensin II-induced pressor response in rats. After intravenous administration
      of 1 and 3 microg/kg 12-HETE, the angiotensin II-induced pressor response was not
      potentiated. However, 10, 20 and 30 min after the administration of 10 microg/kg
      12-HETE, the angiotensin II-induced pressor responses were increased by 7.5, 6.8
      and 4.8 mm Hg, respectively. The significant pressor response was observed at 10
      and 20 min after the administration. In this study, we clearly demonstrated that
      12-HETE potentiated the angiotensin II-induced pressor response.

PMID- 11334880
TI  - Mitochondrial uncoupling proteins and phylogenesis--UCP4 as the ancestral
      uncoupling protein.
AB  - We searched for the previously defined uncoupling protein (UCP) signatures
      [Jezek, P. and Urbankova, E. (2000) IUBMB Life 49, 63-70] in genomes of
      Drosophila melanogaster, Caenorhabditis elegans, Dictyostelium discoideum, and
      Arabidopsis thaliana. We identified four UCPs in Drosophila and one in
      Caenorhabditis or Dictyostelium as close relatives of human UCP4 (BMCP), but
      distant from UCP1, UCP2, UCP3, and two plant UCPs of Arabidopsis. But the third
      Arabidopsis UCP is the closest UCP4 relative. This suggests that UCP4 represents
      the ancestral UCP from which other mammalian and plant UCPs diverged.
      Speculations on UCP4 participation in apoptosis are thus supported by its early
      phylogenetic occurrence.

PMID- 11334881
TI  - Inhibition of cytokine-induced vascular cell adhesion molecule-1 expression;
      possible mechanism for anti-atherogenic effect of Agastache rugosa.
AB  - Adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1) play an
      important role during the early stages of atherogenesis. Agastache rugosa has an
      anti-atherogenic effect in low density lipoprotein receptor -/- mice. Moreover,
      A. rugosa reduced macrophage infiltration and VCAM-1 expression has been
      localized in aortic endothelium that overlies early foam cell lesions. This study
      ascertained that tilianin (100 microM), a major component of A. rugosa, inhibits
      the tumor necrotic factor-alpha (TNF-alpha)-induced expression of VCAM-1 by 74%
      in cultured human umbilical vein endothelial cells (HUVECs). Also, tilianin (100
      microM) reduced TNF-alpha-induced activation of nuclear factor-kappaB in HUVECs.

PMID- 11334882
TI  - A yeast two-hybrid study of human p97/Gab2 interactions with its SH2 domain
      containing binding partners.
AB  - p97/Gab2 is a recently characterized member of a large family of scaffold
      proteins that play essential roles in signal transduction. Gab2 becomes tyrosine
      phosphorylated in response to a variety of growth factors and forms
      multimolecular complexes with SH2 domain-containing signaling molecules such as
      the p85-regulatory subunit of the phosphoinositide-3-kinase (p85-PI3K), the
      tyrosine phosphatase SHP-2 and the adapter protein CrkL. To characterize the
      interactions between Gab2 and its SH2-containing binding partners, we designed a
      modified yeast two-hybrid system in which the Lyn tyrosine kinase is expressed in
      a regulated manner in yeast. Using this assay, we demonstrated that p97/Gab2
      specifically interacts with the SH2 domains of PI3K, SHP-2 and CrkL. Interaction
      with p85-PI3K is mediated by tyrosine residues Y452, Y476 and Y584 of Gab2, while
      interaction with SHP-2 depends exclusively on tyrosine Y614. CrkL interaction is
      mediated by its SH2 domain recognizing Y266 and Y293, despite the latter being in
      a non-consensus (YTFK) environment.

PMID- 11334883
TI  - Conventional protein kinase C isoforms and cross-activation of protein kinase A
      regulate cardiac Na+ current.
AB  - We tested the hypothesis that specific isoforms of protein kinase C (PKC) are
      responsible for modulation of Na+ current (I(Na)) derived from the human cardiac
      Na+ channel using activators and inhibitors selective for specific PKCs.
      Experimental results demonstrated that I(Na) suppression was mediated by
      activation of conventional PKCs (cPKCs) and possibly resulted from channel
      internalization. In the presence of cPKC inhibition, phorbol ester application
      unexpectedly increased Na+ current, an effect eliminated by inhibition of protein
      kinase A. These findings demonstrate complex modulation of cardiac I(Na) by
      protein kinases and provide further evidence that PKC isoforms have distinct
      protein targets.

PMID- 11334885
TI  - Modulation of ribosomal recruitment to 5'-terminal start codons by translation
      initiation factors IF2 and IF3.
AB  - Sequence determinants and structural features of the RNA govern mRNA-ribosome
      interaction in bacteria. However, ribosomal recruitment to leaderless mRNAs,
      which start directly with the AUG start codon and do not bear a Shine-Dalgarno
      sequence like canonical mRNAs, does not appear to rely on 16S rRNA-mRNA
      interactions. Here, we have studied the effects of translation initiation factors
      IF2 and IF3 on 30S initiation at a 5'-terminal AUG and at a competing downstream
      canonical ribosome binding site. We show that IF2 affects the forward kinetics of
      30S initiation complex formation at the 5'-terminal AUG as well as the stability
      of these complexes. Moreover, the IF2:IF3 molar ratio was found to play a
      decisive role in translation initiation of a leaderless mRNA both in vitro and in
      vivo indicating that the translational efficiency of an mRNA is not only
      intrinsically determined but can be altered depending on the availability of
      components of the translational machinery.

PMID- 11334886
TI  - Tyrosine 331 and phenylalanine 334 in Clostridium perfringens alpha-toxin are
      essential for cytotoxic activity.
AB  - Differences in the biological properties of the Clostridium perfringens
      phospholipase C (alpha-toxin) and the C. bifermentans phospholipase C (Cbp) have
      been attributed to differences in their carboxy-terminal domains. Three residues
      in the carboxy-terminal domain of alpha-toxin, which have been proposed to play a
      role in membrane recognition (D269, Y331 and F334), are not conserved in Cbp (Y,
      L and I respectively). We have characterised D269Y, Y331L and F334I variant forms
      of alpha-toxin. Variant D269Y had reduced phospholipase C activity towards
      aggregated egg yolk phospholipid but increased haemolytic and cytotoxic activity.
      Variants Y331L and F334I showed a reduction in phospholipase C, haemolytic and
      cytotoxic activities indicating that these substitutions contribute to the
      reduced haemolytic and cytotoxic activity of Cbp.

PMID- 11334884
TI  - Inhibition of endothelial cell migration by cerivastatin, an HMG-CoA reductase
      inhibitor: contribution to its anti-angiogenic effect.
AB  - Recent studies have suggested that inhibitors of 3-hydroxy-3-methyl-glutaryl
      coenzyme A reductase (statins) can play a role in protection against vascular
      risk, which is independent of cholesterol reduction. It could act by inhibiting
      the synthesis of isoprenoids (farnesylpyrophosphate (FPP) and
      geranylgeranylpyrophosphate (GGPP)), which are respectively essential for
      membrane attachment and biological activity of GTPases Ras and RhoA. This study
      demonstrates that a statin (cerivastatin) inhibits angiogenesis. This effect was
      due to a decrease in endothelial cell locomotion which was reversed by GGPP. It
      was mainly related to delocalization of RhoA from cell membrane to cytoplasm,
      responsible for the disorganization of actin stress fibers. Furthermore, a
      decrease in MMP-2 secretion, involved in cell invasion, was also observed. This
      effect is rather due to Ras inhibition as it was reversed by FPP. This anti
      angiogenic activity could explain the beneficial effect of statins on
      atherosclerosis and on cancer prevention as shown by clinical studies.

PMID- 11334887
TI  - Evolution and function of the neisserial dam-replacing gene.
AB  - Phase variation through slippage-like mechanisms involving homopolymeric tracts
      depends in part on the absence of Dam-methylase in several pathogenic isolates of
      Neisseria meningitidis. In Dam-defective strains drg (dam-replacing gene),
      flanked by pseudo-transposable small repeated elements (SREs), replaced dam. We
      demonstrate that drg encodes a restriction endonuclease (NmeBII) that cleaves 5'
      GmeATC-3'. drg is also present in 50% of Neisseria lactamica strains, but in most
      of them it is inactive because of the absence of an SRE-providing promoter. This
      is associated with the presence of GATmeC, suggesting an alternative restriction
      modification system (RM) specific for 5'-GATC-3', similar to Sau3AI-RM of
      Staphylococcus aureus 3A, Lactococcus lactis KR2 and Listeria monocytogenes.

PMID- 11334888
TI  - Amyloid fibril formation by a helical cytochrome.
AB  - The substitution of alanines for the two cysteines which form thioether linkages
      to the haem group in cytochrome c(552) from Hydogenobacter thermophilus
      destabilises the native protein fold. The holo form of this variant slowly
      converts into a partially folded apo state that over prolonged periods of time
      aggregates into fibrillar structures. Characterisation of these structures by
      electron microscopy and thioflavin-T binding assays shows that they are amyloid
      fibrils. The data demonstrate that when the native state of this cytochrome is
      destabilised by loss of haem, even this highly alpha-helical protein can form
      beta-sheet structures of the type most commonly associated with protein
      deposition diseases.

PMID- 11334889
TI  - Superoxide dismutases enhance H2O2-induced DNA damage and alter its site
      specificity.
AB  - Superoxide dismutases (SODs) are involved in the protection of cells from oxygen
      toxicity. However, several papers have reported that the overexpression of CuZn
      SOD causes oxidative damage to cells. We investigated a mechanism by which an
      excess of SODs accelerates oxidative stress. The presence of CuZn-SOD, Mn-SOD or
      Mn(II) enhanced the frequency of DNA damage induced by hydrogen peroxide (H2O2)
      and Cu(II), and altered the site specificity of the latter: H2O2 induced Cu(II)
      dependent DNA damage with high frequency at the 5'-guanine of poly G sequences;
      when SODs were added, the frequency of cleavages at thymine and cytosine residues
      increased. SODs also enhanced the formation of 8-oxo-7,8-dihydro-2'
      deoxyguanosine by H2O2 and Cu(II). We conclude that SODs may increase
      carcinogenic risks, e.g. of tumors in Down syndrome.

PMID- 11334890
TI  - Mechanisms of tetraethylammonium ion block in the KcsA potassium channel.
AB  - We report results from automated docking and microscopic molecular dynamics
      simulations of the tetraethylammonium (TEA) complexes with KcsA. Binding modes
      and energies for TEA binding at the external and internal sides of the channel
      pore are examined utilising the linear interaction energy method. Effects of the
      channel ion occupancy (based on our previous results for the ion permeation
      mechanisms) on the binding energies are considered. Calculations show that TEA
      forms stable complexes at both the external and internal entrances of the
      selectivity filter. Furthermore, the effects of the Y82V mutation are evaluated
      and the results show, in agreement with experimental data, that the mutant has a
      significantly reduced binding affinity for TEA at the external binding site,
      which is attributed to stabilising hydrophobic interactions between the ligand
      and the tyrosines.

PMID- 11334891
TI  - Angiotensin II type 1 receptor expression in human pancreatic cancer and growth
      inhibition by angiotensin II type 1 receptor antagonist.
AB  - We investigated the expression of angiotensin II type 1 receptor (AT1) in
      pancreatic cancer. Both AT1 mRNA and protein were expressed in human pancreatic
      cancer tissues and cell lines. Binding assays showed that pancreatic cancer cells
      have specific binding sites for angiotensin II and that binding could be
      eliminated by treatment with a selective AT1 antagonist in a dose-dependent
      fashion. Surprisingly, the growth of cancer cells was significantly suppressed by
      treatment with antagonist, also in a dose-dependent manner. These observations
      suggest AT1 plays an important role in pancreatic cancer growth. Furthermore,
      ligand-induced inhibition of AT1 may be a useful therapeutic strategy.

PMID- 11334892
TI  - Human immunodeficiency virus and assisted reproduction: reconsidering evidence,
      reframing ethics.
AB  - OBJECTIVE: To review the advances in the treatment of human immunodeficiency
      virus (HIV) infection and revisit the medical, ethical, and legal issues
      surrounding infertility management in HIV-infected couples. DESIGN: Analytic
      review. RESULTS(S): HIV infection continues to be a serious public health and
      reproductive issue. However, present policies which allow for the categorical
      exclusion of HIV-infected individuals from infertility services should be
      reconsidered in light of improvements in the prognosis of infected individuals
      and a dramatic decrease in the risk of vertical transmission. An analysis of the
      ethical cogency of the arguments against the provision of services does not
      substantiate the exclusion of HIV-infected individuals; rather, the principle of
      justice requires that HIV-infected women be treated the same way as a woman who
      might have an increased risk of conceiving a child with a disability or a may
      have a decreased life expectancy due to a chronic illness such as diabetes.
      Ethical disagreement notwithstanding, with the precedents recently established by
      the Americans with Disabilities Act (ADA), discrimination based on HIV status
      would also likely be unlawful under most circumstances. CONCLUSIONS(S): With
      advances in the treatment of HIV infection, contextualized counseling and a
      respect for patients' decisions regarding infertility treatment should be adopted
      as public policy. It is neither ethically nor legally justifiable to
      categorically exclude individuals from infertility services on the basis of HIV
      infection.

PMID- 11334893
TI  - Using metaphor to deal with human immunodeficiency infection and infertility.

PMID- 11334894
TI  - Preconception gender selection for nonmedical reasons.

PMID- 11334895
TI  - Use of the novel combined contraceptive vaginal ring NuvaRing for ovulation
      inhibition.
AB  - OBJECTIVE: To assess the effects of the combined contraceptive vaginal ring
      NuvaRing on ovarian function. DESIGN: Randomized, open-label, crossover study.
      SETTING: Clinical pharmacology unit. PARTICIPANT(S): Sixteen healthy female
      volunteers. INTERVENTION(S): Group 1: one cycle of combined oral contraceptive
      containing desogestrel (150 microg) and ethinyl estradiol (30 microg)
      (desogestrel/EE COC), followed by a NuvaRing treatment period. Group 2: NuvaRing
      treatment period followed by a cycle of desogestrel/EE COC. MAIN OUTCOME
      MEASURE(S): Follicular diameter, serum hormone concentrations (follicle
      stimulating hormone, 17beta estradiol, luteinizing hormone, and progesterone),
      and endometrial thickness. RESULT(S): NuvaRing use for the recommended period of
      3 weeks resulted in complete inhibition of ovulation, as assessed by vaginal
      ultrasound (follicular diameter) and by serum luteinizing hormone and
      progesterone concentrations. Inhibition of ovulation was maintained for an
      additional 2 weeks of NuvaRing use. Ovarian suppression between the groups was
      comparable. Furthermore, ovarian suppression after 3 weeks of NuvaRing use was
      comparable to that on day 21 of DGS/EE COC intake. NuvaRing was well tolerated.
      CONCLUSION(S): NuvaRing completely inhibited ovulation throughout the normal 3
      week period and the extended period of use. Ovarian suppression was comparable to
      that with desogestrel/EE COC.

PMID- 11334896
TI  - Magnitude and variability of sequential estradiol and progesterone concentrations
      in women using depot medroxyprogesterone acetate for contraception.
AB  - OBJECTIVE: To describe the magnitude and variability of sequential serum
      estradiol and progesterone concentrations throughout one depot
      medroxyprogesterone (DMPA) injection interval. DESIGN: Prospective study.
      SETTING: Family planning and women's health clinics. PATIENT(S): Thirty-one
      women, ages 19 to 46, using DMPA for contraception. INTERVENTION(S): Serum for
      estrogen and progesterone was collected weekly throughout one DMPA injection
      interval. MAIN OUTCOME MEASURE(S): Serum estradiol and progesterone
      concentrations; estradiol patterns produced from data plotted across the entire
      DMPA injection interval. RESULT(S): The average daily estradiol concentrations
      ranged from 7.9 to 69.1 pg/mL, with a mean of 18.9 +/- 12.9 and a median of 15.4
      pg/mL. Average daily progesterone concentrations ranged from 0.14 to 1.1 ng/mL,
      with a mean of 0.40 +/- 0.19 ng/mL and a median of 0.36 ng/mL. Two general
      patterns of estradiol concentrations were identified. One pattern, observed in
      approximately one third of the participants, reflected estradiol concentrations
      that were extremely low (mean, 12.7 +/- 3.6 pg/mL; median, 13.4 pg/mL) and
      consistently flat across the DMPA injection interval. The second pattern, seen in
      the remaining participants, reflected estradiol concentrations that were higher
      (mean, 22.2 +/- 14.9 pg/mL; median, 17.3 pg/mL) and quite variable.
      CONCLUSION(S): This study demonstrated that estradiol concentrations were lower
      than the 40 to 50 pg/mL reported in most studies and, for the majority of women,
      varied substantially across the DMPA injection interval.

PMID- 11334897
TI  - Apolipoprotein E alleles in women with polycystic ovary syndrome.
AB  - OBJECTIVE: To investigate the frequency of apoE alleles among women with
      polycystic ovary syndrome. DESIGN: Retrospective case-control study. SETTING:
      University-based endocrinology/infertility clinic. PATIENT(S): Healthy fertile
      women (n = 91) and women with a diagnosis of polycystic ovary syndrome (n = 58).
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The presence of the three most
      common apoE alleles (epsilon2, epsilon3, and epsilon4) determined by polymerase
      chain reaction-restriction fragment length polymorphism in the two groups and in
      the general population in our area. RESULT(S): The frequency of the apo epsilon4
      allele was 17.2% among women with polycystic ovary syndrome and was 18.7% among
      healthy fertile women, which is close to the rate in the general population in
      our area (19%). None of the apoE genotypes (Fisher's exact test; P=.71) or
      alleles (P=.78) was significantly overrepresented, and the homozygous genotype
      epsilon4 was not associated with the clinical disease. CONCLUSION(S): The
      observed profiles of allele and genotype frequencies confirm the equilibrium
      state between apoE polymorphism and polycystic ovary syndrome and suggest that
      apoE does not play a major role in the development of hyperlipidemia in the group
      of women with polycystic ovary syndrome.

PMID- 11334898
TI  - Dynamics of bioactive follicle-stimulating hormone secretion in women with
      polycystic ovary syndrome: effects of estradiol and progesterone.
AB  - OBJECTIVE: To determine the nature of bioactive FSH secretion in anovulatory
      women with polycystic ovary syndrome (PCOS) and its modulation by luteal levels
      of E2 and P. DESIGN: Interventional and observational study. SETTING: Academic
      clinical research center. PATIENT(S): Five patients with PCOS. INTERVENTION(S):
      Treatment for 21 days with luteal levels of E2 and P. MAIN OUTCOME MEASURES:
      Serum levels of immunoreactive LH, immunoreactive FSH, bioreactive FSH, and the
      FSH isoform distribution pattern. Blood was sampled frequently and GnRH testing
      was done on day 0 (before treatment), days 10 and 20 (during treatment), and day
      28 (7 days after treatment). RESULT(S): Treatment with E2 and P suppressed
      circulating immunoreactive LH and immunoreactive FSH but not bioreactive FSH.
      Anovulatory women with PCOS showed a predominantly acidic pattern of FSH isoform
      distribution. Treatment with E2 and P shifted the distribution profile of FSH
      isoforms to the less acidic. After cessation of E2-P treatment, FSH reverted to
      its pretreatment pattern of distribution. CONCLUSION(S): Resumption of follicular
      growth after luteal replacement of E2 and P in anovulatory women with PCOS may be
      related to the reduction in the elevated LH/FSH ratio and accompanying changes in
      the FSH signal.

PMID- 11334899
TI  - Hyperandrogenemia in patients presenting with acne.
AB  - OBJECTIVE: To determine whether acne is associated with hyperandrogenemia,
      regardless of age of presentation. DESIGN: Prospective controlled study. SETTING:
      Tertiary-care medical center. PATIENT(S): Thirty consecutive unselected women
      presenting with acne and no hirsutism and 24 eumenorrheic healthy controls.
      INTERVENTION(S): Serum samples was taken in all patients, and an acute 60-minute
      ACTH-(1-24) test was performed in 19 patients. MAIN OUTCOME MEASURE(S): Total and
      free T, sex hormone-binding globulin (SHBG), and DHEAS levels in basal samples,
      and ACTH-stimulated 17-hydroxyprogesterone (17-HP) response to exclude 21
      hydroxylase (21-OH)-deficient nonclassic adrenal hyperplasia (NCAH) were
      determined. RESULT(S): Nonhirsute patients with acne demonstrated significantly
      lower levels of SHBG and higher free-T and DHEAS levels than controls. Nineteen
      (63%) acneic patients had at least one androgen value above the 95% of controls.
      In patients aged 12-18 years, 7/8 (88%) had at least one increased androgen
      value, compared with 12/22 (55%) patients aged 19-43 years. One patient (5.3%)
      was found to have 21-OH-deficient NCAH. CONCLUSION(S): Hyperandrogenemia was
      evident in a majority of nonhirsute acneic patients studied, regardless of age.
      These data suggest that androgen suppression may be useful in treating acne in
      many of these patients.

PMID- 11334900
TI  - How do patients choose private in vitro fertilization treatment? A customer
      survey in a tertiary fertility center in the United Kingdom.
AB  - OBJECTIVE: To assess the relevant factors affecting patients' decision when
      choosing a clinic for private, self-funded IVF treatment. DESIGN: Prospective
      anonymous closed questionnaires. SETTING: Single tertiary-care private IVF
      center. PATIENT(S): New patients attending primary consultation in a period of 7
      months from September 1999 to March 2000. INTERVENTION(S): None. MAIN OUTCOME
      MEASURE(S): Primary knowledge about the clinic, source of referral, knowledge of,
      availability of information pack, and familiarity with the clinic's success rates
      and treatment's price. The last question assessed the relative importance of each
      factor in the decision-making process according to the SERVQUAL model, modified
      version. All items were measured as perceptions on a 5-point Likert scale. 1 =
      not important, 3 = neutral, and 5 = very important. RESULTS(S): One hundred
      seventy-five patients completed the questionnaire. They were well informed and
      investigated the market before making their final choice. Patients collect
      information from many sources, including new channels such as the Internet. Up to
      one third of patients do not consult their doctor before treatment. By far the
      most relevant factor in decision making is the success rate (i.e., delivery
      rates) of the clinic, followed by recommendation by general practitioner (GP) or
      consultant (respectively, Likert scale score, 4.6; 95% confidence interval [CI],
      4.5-4.7; and Likert scale score, 4.0; 95% CI, 3.9-4.2; P<.01). Other factors,
      such as cost of the treatment, friends and relatives' opinions, and distance from
      home were not relevant. CONCLUSION(S): Units that wish to thrive and increase
      their market share should deliver high-quality service and concentrate their
      efforts on excelling in performance.

PMID- 11334901
TI  - Effects of postmenopausal hormone replacement therapy on lipid, lipoprotein, and
      apolipoprotein (a) concentrations: analysis of studies published from 1974-2000.
AB  - OBJECTIVE: To establish reference estimates of the effects of different hormone
      replacement therapy (HRT) regimens on lipid and lipoprotein levels. DESIGN:
      Review and pooled analysis of prospective studies published up until the year
      2000. SETTING: Clinical trials centers, hospitals, menopause clinics. PATIENT(S):
      Healthy postmenopausal women. INTERVENTION(S): Estrogen alone, estrogen plus
      progestogen, tibolone, or raloxifene in the treatment of menopausal symptoms.
      MAIN OUTCOME MEASURE(S): Serum high- and low-density lipoprotein (HDL and LDL)
      cholesterol, total cholesterol, triglycerides, and lipoprotein (a). RESULT(S):
      Two-hundred forty-eight studies provided information on the effects of 42
      different HRT regimens. All estrogen alone regimens raised HDL cholesterol and
      lowered LDL and total cholesterol. Oral estrogens raised triglycerides.
      Transdermal estradiol 17-beta lowered triglycerides. Progestogens had little
      effect on estrogen-induced reductions in LDL and total cholesterol. Estrogen
      induced increases in HDL and triglycerides were opposed according to type of
      progestogen, in the order from least to greatest effect: dydrogesterone and
      medrogestone, progesterone, cyproterone acetate, medroxyprogesterone acetate,
      transdermal norethindrone acetate, norgestrel, and oral norethindrone acetate.
      Tibolone decreased HDL cholesterol and triglyceride levels. Raloxifene reduced
      LDL cholesterol levels. In 41 studies of 20 different formulations, HRT generally
      lowered lipoprotein (a). CONCLUSION(S): Route of estrogen administration and type
      of progestogen determined differential effects of HRT on lipid and lipoprotein
      levels. Future work will focus on the interpretation of the clinical significance
      of these changes.

PMID- 11334902
TI  - Factor XII but not protein C, protein S, antithrombin III, or factor XIII is a
      predictor of recurrent miscarriage.
AB  - OBJECTIVE: To investigate whether a decrease in the values of protein C (PC),
      protein S (PS), antithrombin III (ATIII), factor XII (FXII), or factor XIII
      (FXIII) has predictive value for subsequent miscarriages. DESIGN: Prospective
      study. SETTING: Nagoya City University Medical School. PATIENT(S): A total of 536
      patients with a history of two or more first-trimester miscarriages.
      INTERVENTION(S): One hundred and twelve patients treated with low-dose aspirin
      were excluded from the analysis. MAIN OUTCOME MEASURE(S): The subsequent
      pregnancy outcome of 424 patients was compared for abnormal and normal levels of
      each parameter. RESULT(S): There were no differences in the subsequent
      miscarriage rates between abnormal and normal values of PC, PS, ATIII, and FXIII.
      However, the rate with abnormal FXII is significantly higher than that with
      normal FXII. CONCLUSION(S): A decrease in FXII (but not in PC, PS, ATIII, or
      FXIII) predicts subsequent miscarriage in patients with a history of first
      trimester recurrent miscarriages.

PMID- 11334903
TI  - Clinical experience with recombinant follicle-stimulating hormone (FSH) and
      urinary FSH: a retrospective case- controlled analysis.
AB  - OBJECTIVE: To compare the efficacy and efficiency of recombinant FSH (rFSH) and
      urinary FSH (uFSH). DESIGN: Retrospective case controlled analysis. SETTING: An
      assisted reproduction unit at a university center. PATIENT(S): 1388 patients
      undergoing long protocol in vitro fertilization/embryo transfer (IVF-ET) using
      buserelin acetate from day 2 of the cycle and either rFSH (follitropin beta) (n =
      694) or uFSH (n = 694) with equal number of ampules started (rFSH: 50 IU, uFSH:
      75 IU). INTERVENTION(S): Patients were included in the two groups of treatment
      after matching for similarity in age and type of treatment (IVF or
      intracytoplasmic sperm injection). MAIN OUTCOME MEASURE(S): Total dose of FSH,
      ovarian response, and IVF outcome. RESULT(S): Patients who received uFSH
      experienced a shorter period of stimulation, and a higher number of oocytes were
      collected. The total FSH used was lower in the rFSH group, and they required a
      lower FSH dose per oocyte retrieved. The implantation and pregnancy rates were
      similar between the uFSH and rFSH groups. In both groups implantation and
      pregnancy rates were higher when intracytoplasmic sperm injection was performed
      as compared with IVF. CONCLUSION(S): The implantation and pregnancy rates are
      similar when either rFSH or uFSH is used (when compared on an ampule-to-ampule
      basis, rFSH: 50 IU, and uFSH: 75 IU). However, a significantly lower total FSH
      dose was used in the rFSH group with a lower FSH dose per oocyte collected.

PMID- 11334904
TI  - Endocrine and chronobiological effects of fasting in women.
AB  - OBJECTIVE: To determine whether fasting in women would suppress GnRH/LH drive in
      a high- versus low-gonadal steroid milieu. DESIGN: Case-control study. SETTING:
      Academic clinical research center. PATIENT(S): Eleven eumenorrheic women and
      eleven women taking combined oral contraceptives. INTERVENTION(S): Seven of the
      eleven women in each group underwent an acute 72-hour fast. Blood samples were
      obtained at 15-minute intervals for 24 hours before the fast and during the last
      24 hours of fasting. MAIN OUTCOME MEASURE(S): Twenty-four-hour profiles of LH,
      cortisol, and melatonin were assessed. Ovarian activity was tracked with
      estradiol and progesterone levels, and metabolic responses were gauged by
      measuring thyroid hormone and beta-hydroxy-butyric acid levels. RESULT(S):
      Fasting increased beta-hydroxy-butyric acid and reduced free thyronine. Fasting
      in the midfollicular phase had no effect on LH pulsatility or on FSH, estradiol,
      or subsequent luteal-phase progesterone levels. However, fasting elevated
      cortisol and resulted in a phase advance in melatonin secretion of 81 minutes in
      both the midfollicular and luteal phases. CONCLUSION(S): Fasting in women
      elicited expected metabolic responses and apparently advanced the central
      circadian clock without compromising reproductive function.

PMID- 11334906
TI  - Regulation of human oviductin mRNA expression in vivo.
AB  - OBJECTIVE: To examine changes in oviductin mRNA expression in oviductal mucosal
      tissue from fertile women throughout an ovulatory cycle. DESIGN: Semiquantitative
      reverse-transcriptase-polymerase chain reaction (RT-PCR) analysis of oviductin
      mRNA. SETTING: University-based obstetrics and gynecology department. SUBJECT(S):
      Twenty women undergoing laparoscopy for tubal sterilization or hysterectomy for
      uterine fibroids. INTERVENTION(S): The mucosal layer was isolated from the
      oviduct tissue, and semiquantitative RT-PCR was performed. MAIN OUTCOME
      MEASURE(S): The relationship between serum estradiol, luteinizing hormone, and
      progesterone concentrations and the expression of oviductin mRNA. RESULT(S):
      There was a significant positive correlation between serum estradiol and
      luteinizing hormone concentrations and oviductin mRNA expression. There was a
      significant inverse correlation between serum progesterone concentrations and
      oviductin mRNA expression. CONCLUSION(S): Little is known about the regulation of
      human oviductin. This study was the first to examine the relationship between
      oviductin mRNA expression and serum estradiol and luteinizing hormone and
      progesterone concentrations in fertile women. Estradiol and luteinizing hormone
      both have a stimulatory effect on oviductin mRNA in humans, however, it is
      difficult to determine whether the effects are independent of one another, as the
      luteinizing hormone surge is dependent on the estradiol increase. Progesterone
      shows a clear inhibitory effect on oviductin mRNA.

PMID- 11334905
TI  - Altered osmotic thresholds for arginine vasopressin secretion and thirst during
      superovulation and in the ovarian hyperstimulation syndrome (OHSS): relevance to
      the pathophysiology of OHSS.
AB  - OBJECTIVE: To test the hypothesis that decreases in and maintenance of a new
      steady state in plasma osmolality and sodium level in ovarian hyperstimulation
      syndrome (OHSS) are due to altered osmoregulation of arginine vasopressin
      secretion and thirst. DESIGN: Prospective study. SETTING: IVF-ET program in a
      university-based assisted reproductive treatment center. PATIENT(S): Eight women
      undergoing superovulation for IVF-ET and five women with normal menstrual cycles.
      INTERVENTION(S): Two-hour infusion of 5% saline on day 3 or 4 after hCG
      administration in patients undergoing IVF or in the early luteal phase in
      controls. A 5% saline infusion test was done on day 10 after hCG administration
      in one patient with OHSS and one patient without OHSS, both of whom were
      undergoing IVF. MAIN OUTCOME MEASURE(S): Comparison of changes in thresholds for
      thirst and plasma vasopressin to plasma osmolality. Changes in urine osmolality,
      plasma electrolytes, hemoglobin level, and hematocrit were assessed at baseline
      and during infusion of 5% saline. RESULT(S): The sensitivity of the changes in
      arginine vasopressin secretion and thirst after 5% saline infusion was similar in
      IVF patients on day 3 or 4 after hCG and controls. However, the osmotic threshold
      was significantly lower by 6 mOsm/kg in IVF patients. By day 10 after hCG, the
      lower osmotic thresholds for arginine vasopressin secretion and thirst persisted
      in OHSS, although the sensitivity to arginine vasopressin secretion was markedly
      reduced. CONCLUSION(S): The osmotic thresholds for arginine vasopressin secretion
      and thirst are reset to lower plasma osmolality during superovulation for IVF-ET.
      This new lower body tonicity is maintained until at least day 10 after hCG in
      OHSS. Decreases in plasma osmolality and plasma sodium levels in OHSS are due to
      altered osmoregulation rather than electrolyte losses; correction of apparent
      "electrolyte imbalance" in OHSS is therefore inappropriate.

PMID- 11334907
TI  - Application of complementary DNA microarray (DNA chip) technology in the study of
      gene expression profiles during folliculogenesis.
AB  - OBJECTIVE: Using oligonucleotide microarray (DNA chip)-based hybridization
      analysis to gain a comprehensive view of gene expression and regulation involved
      in folliculogenesis. DESIGN: Prospective randomized study. SETTING: Academic
      institution. ANIMAL(S): B6D2F1 female mice. INTERVENTION(S): Superovulation. MAIN
      OUTCOME MEASURE(S): Preantral follicles isolated from day 14 B6D2F-1 mice were
      stimulated in vitro to form Graafian follicles. Total RNA extracted from the
      mouse preantral and Graafian follicles were reverse transcribed, labeled with
      digoxigenin-11-dUTP, and then hybridized with Clontech Atlas mouse cDNA
      expression arrays for comparison. RESULT(S): Of 588 known studied genes, 39 and
      61 were detected in preantral follicles and in Graafian follicles, respectively,
      and 17 were highly expressed consistently in both preantral and Graafian
      follicles. Performing clustering analysis, we found that 15 detected genes were
      down-regulated and 46 were up-regulated as the follicles advanced to mature
      stages. CONCLUSION(S): We have successfully developed a sensitive DNA chip
      technology that is able to simultaneously and quantitatively study gene
      expression profiles in a small number of follicles (1.5-15 follicles). Several
      folliculogenesis-related genes have been identified. Some of these genes were
      expressed, indicating that they may be essential for follicle growth and
      maturation, whereas others were up-regulated only during late follicular
      development, indicating stage-specific roles.

PMID- 11334908
TI  - Expression of the cyclin-dependent kinase inhibitor p27Kip1 in eutopic
      endometrium and peritoneal endometriosis.
AB  - OBJECTIVE: This study was undertaken to evaluate the immunohistochemical
      expression of the cell cycle inhibitor p27Kip1 and proliferation marker Ki67 in
      peritoneal endometriosis and eutopic endometrium. DESIGN: Prospective study.
      SETTING: University hospital. PATIENT(S): Thirty-one patients with peritoneal
      endometriosis. INTERVENTION(S): During laparoscopy, 25 samples of predominantly
      red peritoneal lesions and 27 samples of predominantly black peritoneal lesions
      were collected from 31 patients with endometriosis. Eutopic endometrium from 25
      patients with endometriosis was collected by curettage during laparoscopy or just
      after surgery. MAIN OUTCOME MEASURE(S): The percentage of glandular and stromal
      cells exhibiting positive staining for p27Kip1 and Ki67 (labeling index, LI) was
      determined. RESULT(S): The LI of stromal cells in red peritoneal lesions for both
      p27Kip1 and Ki67 was similar to that of proliferative eutopic endometrium.
      Although the LI of glandular epithelial cells for Ki67 in red lesions was
      comparable to that of proliferative eutopic endometrium, the LI for p27Kip1 was
      significantly higher. Furthermore, we detected a significantly higher LI of
      glandular epithelial and stromal cells for p27Kip1 in black lesions compared with
      red lesions. CONCLUSION(S): Our results suggest that expression of the cyclin
      kinase inhibitor p27Kip1 is involved in the natural history and progression of
      peritoneal endometriosis.

PMID- 11334909
TI  - Determination of the ultrastructural pathology of human sperm by atomic force
      microscopy.
AB  - OBJECTIVE: To investigate ultrastructural changes, particularly at the surface,
      that occur in pathological spermatozoa by using atomic force microscopy (AFM) and
      to examine the morphological alterations responsible for infertile sperm. DESIGN:
      Normal fertile and pathological spermatozoa were examined by using a conventional
      AFM in a noncontact mode. SETTING: Andrology clinic at Los Andes University
      Hospital. PATIENT(S): Sperm of patients with oligoasthenoteratozoospermia (OAT)
      and asthenozoospermia were obtained from the Los Andes University Hospital,
      Merida, Venezuela. INTERVENTION(S):  MAIN OUTCOME MEASURE(S): Morphological
      details, topological information, and three-dimensional images of the head, neck,
      and flagellum are presented for both normal and pathological sperm. RESULT(S):
      The obtained images clearly show dramatic alterations in the morphology of the
      head, neck, and flagellum of pathological sperm. Even the ultrastructure at the
      top of the flagellum and the region of the acrosome cap are clearly
      distinguishable. CONCLUSION(S): This study has significant importance not only
      for identifying spermatozoa alterations but also for understanding morphological
      defects and their effects on infertility. If properly exploited, this technique
      could be an important research tool.

PMID- 11334910
TI  - Presence of a 31-kD protein band in human cumulus--corona radiata--conditioned
      media and pregnancy outcome.
AB  - OBJECTIVE: To investigate relationships between cumulus-oocyte complex (COC)
      morphology, protein patterns of cumulus-corona (CC) cell-conditioned media, and
      pregnancy outcome in IVF-ET cycles. DESIGN: Retrospective study. SETTING: Private
      university IVF center. PATIENT(S): One hundred twenty infertile women who
      underwent IVF-ET procedures. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): COC
      grading, analysis of CC cell morphology and conditioned media, and pregnancy rate
      (PR). RESULT(S): After IVF and embryo transfer, cultured CC cells were classified
      as high (HA) or low (LA) on the basis of their adhesive properties. Neither
      adhesion activity nor fertilization rates and embryo quality were correlated with
      COC grading. PR in cycles with HA cells was 38%, but 14% of cycles showing LA
      activity also had positive outcome. To find more meaningful parameters of CC
      cells useful to predict fertilization and pregnancy, the electrophoretic protein
      patterns of media conditioned by HA or LA cells were studied. Retrospective
      analysis showed that all cycles in which replaced embryos were associated with
      the presence of a 31-kD band in conditioned media failed implantation, whereas
      83% of cycles lacking this band resulted in positive, ongoing pregnancy.
      CONCLUSION(S): Pregnancy prediction cannot rely simply on CC cell morphological
      analysis. Screening of conditioned media may provide more reliable parameters.

PMID- 11334911
TI  - Hepatocyte growth factor and stem cell factor involvement in paracrine interplays
      of theca and granulosa cells in the human ovary.
AB  - OBJECTIVE: To examine gene expression of hepatocyte growth factor (HGF), the
      receptor for HGF, c-met, and the receptor for stem cell factor (SCF), c-kit, in
      the human ovary and to investigate the effects of HGF and SCF on the
      proliferation and function of granulosa and theca cells. DESIGN: Prospective
      study. SETTING: University hospital. PATIENT(S): Six premenopausal women.
      INTERVENTION(S): Follicular fluid and granulosa cells were collected during IVF
      cycles. Ovarian tissues were obtained from women who underwent surgery. MAIN
      OUTCOME MEASURE(S): Gene expression of HGF, c-met, and c-kit in the human ovary
      was determined. RESULT(S): Reverse-transcription polymerase chain reaction showed
      the presence of HGF and c-kit mRNA in the theca and stroma cells of the ovary,
      whereas c-met mRNA was observed in the granulosa, theca, and stroma cells. HGF
      increased the expression of SCF gene in granulosa cells, and SCF reciprocally
      increased the expression of HGF gene in theca cells. SCF stimulated the
      proliferation of theca cells. HGF stimulated progesterone production in granulosa
      cells. CONCLUSION(S): A positive feedback loop between theca cells and granulosa
      cells was identified that is mediated by HGF and SCF. HGF and SCF modulate the
      interplay between theca and granulosa cells by promoting cell proliferation and
      steroid hormone production.

PMID- 11334912
TI  - Glucocorticoid hormone can suppress apoptosis of rat testicular germ cells
      induced by testicular ischemia.
AB  - OBJECTIVE: To evaluate the effect of dexamethasone, a potent synthetic
      glucocorticoid hormone, on apoptosis of testicular germ cells and vascular
      neutrophil adhesion after repair of testicular torsion in rats. DESIGN:
      Controlled laboratory study. SETTING: Department of Urology, Yamagata University
      School of Medicine, Yamagata, Japan. ANIMAL(S): Fifty-one male Sprague-Dawley
      rats. INTERVENTION(S): Dexamethasone, 10 mg/kg of body weight. MAIN OUTCOME
      MEASURE(S): Testicular germ-cell apoptosis (percentages of apoptotic tubules and
      apoptotic cells) and vascular neutrophil adhesion were assessed by using DNA nick
      end labeling and the endothelial-neutrophil adhesion score, respectively.
      RESULT(S): Intravenous administration of dexamethasone at repair of 90-minute
      testicular torsion significantly inhibited testicular germ-cell apoptosis and
      vascular neutrophil adhesion. This inhibition was suppressed by intravenous
      injection of mifepristone, a glucocorticoid-receptor antagonist. CONCLUSION(S):
      Glucocorticoids can be administered for torsion in addition to conventional
      torsion repair.

PMID- 11334913
TI  - The incidence of cytoplasmic fragmentation in mouse embryos in vitro is not
      affected by inhibition of caspase activity.
AB  - OBJECTIVE: To investigate the relationship between cytoplasmic fragmentation and
      caspase activity in the mouse embryo. DESIGN: Experimental laboratory study.
      SETTING: University gynacology unit. ANIMAL(S): One-cell zygote of mouse (MF1 x
      BALB/c). INTERVENTION(S): Mouse embryos were treated with caspase inhibitors:
      benzyloxycarbonyl-Val-Ala-Asp fluoromethylketone (z-VAD-fmk) and
      benzyloxycarbonyl-Asp-glu-Val-Asp-fluoromethyl ketone (Z-DEVD-fmk). MAIN OUTCOME
      MEASURE(S): Morphological development of the embryo, proportion of fragmented
      embryos, caspase-3-like activity, DNA breakage, and phosphatidylserine exposure
      in blastomeres. RESULT(S): The proportion of embryo reaching two-cell, three- to
      four-cell, and morula stage at 48, 72, and 96 hours after hCG administration,
      respectively, were comparable between the control embryos and those treated with
      either z-VAD-fmk or z-DEVD-fmk, at three concentrations (10 microM, 50 microM,
      and 200 microM). Although the inhibitors suppressed the caspase-3-like activity
      in the embryo fragment before compaction and decreased DNA breakages, there was
      no statistically significant difference in the percentage of fragmented embryo
      between the control and those treated with caspase inhibitors. The inhibitors did
      not affect the incidence of phosphatidylserine exposure in the blastomere of the
      treated embryos. CONCLUSION(S): Cytoplasmic fragmentation in precompaction mouse
      embryos is not a consequence of caspase-related apoptosis.

PMID- 11334914
TI  - Localization of interferon regulatory factor-1 in human endometrium throughout
      the menstrual cycle.
AB  - OBJECTIVE: To determine the expression and localization of IRF-1 in human
      endometrium throughout the menstrual cycle. DESIGN: A comparative study. SETTING:
      Department of Obstetrics and Gynecology, Kyoto Prefectural University of
      Medicine. PATIENTS: Thirty-eight women aged 33 to 46 years, with regular
      menstrual cycles and nonpathological endometrium, undergoing hysterectomy.
      INTERVENTION(S): Endometrial tissues were obtained from operative samples. MAIN
      OUTCOME MEASURE(S): Expression of IRF-1 mRNA throughout the menstrual cycle was
      investigated using semiquantitative reverse transcription-polymerase chain
      reaction. Localization of IRF-1 protein was determined using
      immunohistochemistry. RESULT(S): IRF-1 mRNA was expressed in the human
      endometrium at each phase of the menstrual cycle. The immunoreactivity for IRF-1
      was observed in the extranuclear compartment of the surface and glandular
      epithelial cells, both during the proliferative and secretory phases, as well as
      in the gland secretion during the secretory phase. In contrast, stromal cells
      were nearly unstained. CONCLUSION(S): IRF-1 was localized in the human
      endometrium, implying that this nuclear protein plays some role other than as a
      transcription factor.

PMID- 11334915
TI  - Differential effects of insulin-like growth factor-I and gonadotropins on the
      proliferative activity of two subgroups of granulosa cells: cumulus oophorus and
      mural granulosa cells.
AB  - OBJECTIVE: To evaluate the physiological role of insulin-like growth factor-I
      (IGFI) and its interaction with gonadotropins in cell replication of two types of
      granulosa cells (cumulus oophorus, CC) and mural granulosa cells (MGC). DESIGN:
      Controlled randomized study of the action and interaction of gonadotropins and
      IGFI on granulosa cell replication in the rat. SETTING: A university reproductive
      biology laboratory. INTERVENTION(S): The study examined the in vivo treatment
      with gonadotropins or an analogue of IGFI, long Arg3-insulin-like growth factor
      (LR3-IGFI), which does not bind to IGFI-binding proteins. MAIN OUTCOME
      MEASURE(S): Granulosa cell replication was evaluated by the use of 3H-thymidine
      incorporation. RESULT(S): It was noted that the CC replicate much faster than the
      MGC. These two types of granulosa cells have very different dose response curves
      to IGFI. Differential responses were seen in animal cells exposed to long Arg3
      insulin-like growth factor in vivo and then exposed to FSH and LH in vitro.
      CONCLUSION(S): Although murine granulosa cells show proliferative activity when
      they are exposed to IGFI, the two types, CC and MGC, respond differently. IGFI is
      not the sole mediator of the action of FSH, and these two chemicals may act
      independently or in concert.

PMID- 11334916
TI  - Hydrosalpinx fluid affects murine embryonic development in a coculture system
      with epithelial endometrial cells.
AB  - OBJECTIVE: The aim of the present investigation was to assess whether a coculture
      system protects from the effect of hydrosalpinx fluid (HF) on murine embryo
      development, evaluated through blastocyst cell number. DESIGN: Controlled
      prospective study. SETTING: Academic research center. PATIENT(S): Endometrium and
      HF from six patients and endometrium from six normal patients. INTERVENTION(S):
      Murine embryos were exposed to the absence or presence of different
      concentrations of human HF: 0% HF (control), 50% HF, 70% HF in human tubal fluid,
      and 100% HF, in a simple culture system (SCS), epithelial coculture system (ECS),
      and hydrosalpinx epithelial coculture system (HECS). MAIN OUTCOME MEASURE(S):
      Embryonic development at 72 hours and blastocyst cell number determined by the
      Tarcowsky method. RESULT(S): In SCS, 91.9% of the embryos reached the blastocyst
      stage, and no significant differences were shown in the presence of HF. However,
      significant differences were observed in the blastocyst cell number. Of the
      embryos cultured in ECS, 97.1% reached the blastocyst stage, and high
      concentrations of HF caused a decrease in embryonic development. A significant
      difference was observed between ECS and HECS in embryo development without HF.
      When HF was added, a significant decrease in blastocyst cell number was seen in
      embryos exposed to HECS compared with ECS. CONCLUSION(S): Our data suggest that
      normal and hydrosalpinx endometria do not protect from the deleterious effect of
      HF on embryo development at the concentrations evaluated. This effect is dose
      dependent and was determined through the blastocyst cell number.

PMID- 11334917
TI  - Transvaginal hydrolaparoscopy but not standard laparoscopy reveals subtle
      endometriotic adhesions of the ovary.
AB  - OBJECTIVE: To determine whether transvaginal hydrolaparoscopy is superior to
      standard laparoscopy for detection of subtle endometriotic adhesions of the
      ovary. DESIGN: Videotapes of standard laparoscopy and transvaginal
      hydrolaparoscopy were viewed by an independent observer in random order and in a
      blinded manner. SETTING: Tertiary referral centers for infertility. PATIENT(S):
      Patients with minimal or mild endometriosis (n = 11) and unexplained infertility
      (n = 10) on standard laparoscopy from a group of 43 patients with infertility who
      were undergoing both studies. INTERVENTION(S): Transvaginal hydrolaparoscopy
      followed by standard laparoscopy. MAIN OUTCOME MEASURE(S): Detection of
      unexplained ovarian adhesions. RESULT(S): Patients with minimal and mild
      endometriosis and unexplained infertility had significantly more ovarian
      adhesions on transvaginal hydrolaparoscopy than on standard laparoscopy. The
      subtle adhesions seen on transvaginal hydrolaparoscopy but not on standard
      laparoscopy were filmy, microvascularized, and nonconnecting. CONCLUSION(S):
      Unexplained ovarian adhesions are frequently detected on transvaginal
      hydrolaparoscopy but not on standard laparoscopy in infertile patients with
      minimal and mild endometriosis and unexplained infertility.

PMID- 11334918
TI  - Microsurgical varicocelectomy in the era of assisted reproductive technology:
      influence of initial semen quality on pregnancy rates.
AB  - OBJECTIVE: To evaluate the natural history of infertile couples in whom the man
      underwent varicocelectomy. DESIGN: Retrospective study. SETTING: University
      infertility clinic. PATIENT(S): 159 infertile couples. INTERVENTION(S):
      Microsurgical varicocelectomy. MAIN OUTCOME MEASURE(S): Standard semen parameters
      and pregnancy rates (assisted and unassisted). RESULT(S): Postoperative sperm
      concentration and motility increased significantly compared to before the
      varicocelectomy (28.9 +/- 3.0 vs. 22.5 +/- 2.1 x 10(6)/mL and 33.9 +/- 1.9 vs.
      22.1 +/- 1.3%, respectively). Overall, 48% (76/159) of the couples achieved a
      spontaneous pregnancy at the mean of 30 months' follow-up. An additional 10%
      (16/159) and 11% (18/159) of couples achieved a pregnancy following intrauterine
      insemination and in vitro fertilization/intracytoplasmic sperm injection,
      respectively. Significantly higher spontaneous pregnancy rates were observed in
      couples in whom the man's initial sperm concentration was greater than or equal
      to 5 million sperm per milliliter compared to those in whom the man's initial
      sperm concentration was less than 5 million sperm per milliliter (61% vs. 8%,
      respectively). CONCLUSION(S): Our data demonstrate that, in couples in whom the
      man undergoes varicocelectomy for treatment of varicocele, close to 70% achieve a
      pregnancy. The initial sperm concentration is predictive of unassisted pregnancy
      outcome in this population.

PMID- 11334919
TI  - Hydrosalpinx treated with extended doxycycline does not compromise the success of
      in vitro fertilization.
AB  - OBJECTIVE: To determine if extended treatment with doxycycline before and after
      an in vitro fertilization (IVF) procedure can minimize the detrimental effect of
      a hydrosalpinx. DESIGN: Retrospective analysis. SETTING: University IVF program.
      PATIENT(S): Patients undergoing IVF, including 17 with a hydrosalpinx, 25 with
      adhesions or proximal tubal occlusion, and 22 with endometriosis or unexplained
      infertility. INTERVENTION(S): Women with a documented hydrosalpinx were
      prescribed doxycycline 100 mg twice daily starting 1 week before expected
      retrieval and continued until 6 days after retrieval. No antibiotics were
      prescribed in the other groups. MAIN OUTCOME MEASURE(S): Implantation rates and
      IVF outcomes. RESULT(S): Implantation rates were 30% for the doxycycline-treated
      group of patients with a hydrosalpinx, 27% for the group with tubal
      occlusion/adhesion, and 24% for the group with endometriosis or unexplained
      infertility. Eight (47%) of 17 patients with a hydrosalpinx had a live birth,
      compared with 11 (44%) of 25 for the group with tubal occlusion/adhesion and 12
      (55%) of 22 for the group with endometriosis/unexplained infertility. There were
      no differences between the groups in patient age, number of oocytes retrieved,
      fertilization rate, or number of blastomeres of the transferred embryos.
      CONCLUSION(S): No detrimental effect of a hydrosalpinx was evident for patients
      treated with extended doxycycline. Tremendous cost savings can be realized if
      treatment with 2 weeks of an inexpensive antibiotic provides outcomes comparable
      to surgical correction of a hydrosalpinx before IVF.

PMID- 11334920
TI  - Role of the follistatin gene in women with polycystic ovary syndrome.
AB  - OBJECTIVE: To search for mutations in the coding exons of the follistatin gene of
      women diagnosed with polycystic ovary syndrome (PCOS). DESIGN: Controlled
      clinical study. SETTING: Tertiary institutional hospital. PATIENT(S): Thirty-four
      women diagnosed with PCOS and 15 healthy control women. INTERVENTION(S): Whole
      blood and serum samples were collected during the follicular phase of the
      menstrual cycle. MAIN OUTCOME MEASURE(S): Circulating total testosterone (T), sex
      hormone-binding globulin (SHBG), calculated free T (FT), androstenedione (A),
      dehydroepiandrosterone-sulfate (DHEAS), LH, FSH, E2, and basal and
      adenocorticotropic hormone (ACTH)-stimulated 17-hydroxyprogesterone (17-OHP) were
      determined. Insulin resistance was estimated from fasting glucose and insulin
      levels, using the homeostasis model assessment. The coding regions of the
      follistatin gene were studied by heteroduplex analysis after polymerase chain
      reaction amplification. RESULT(S): Women with PCOS presented with higher body
      mass index, insulin resistance, T, FT, A, and ACTH-stimulated 17-OHP serum
      concentrations and lower SHBG serum levels, as compared with controls. No
      differences were observed among the groups in serum DHEAS, basal 17-OHP, E(2),
      LH, and FSH. No mutations were found in coding regions of the follistatin gene,
      with the exception of a G to A change at cDNA position 951, resulting in a silent
      mutation. This change was present in 2 (5.9%) of 34 patients and 1 (6.7%) of 15
      controls. CONCLUSION(S): Mutations in the coding regions of the follistatin gene
      do not appear to be related to PCOS.

PMID- 11334921
TI  - A prospective randomized trial comparing clomiphene citrate with tamoxifen
      citrate for ovulation induction.
AB  - OBJECTIVE: To compare the rates of ovulation and pregnancy after tamoxifen
      citrate (TMX) or clomiphene citrate (CC) among anovulatory women with
      infertility. DESIGN: Prospective randomized trial. SETTING: Infertility clinic in
      a university teaching hospital. PATIENT(S): Eighty-six anovulatory women under 40
      years of age undergoing ovulation induction. INTERVENTION(S): The women were
      assigned randomly to receive either TMX or CC on cycle days 5-9. MAIN OUTCOME
      MEASURE(S): Rates of ovulation and pregnancy for the two treatment modalities.
      RESULTS(S): The overall rate of ovulation in the TMX group was 50 of 113 (44.2%)
      and in the CC group, 41 of 91 (45.1%). There were 10 pregnancies in the TMX group
      and 6 pregnancies in the CC group. The cycle fecundity per ovulatory cycle was
      20.0% in the TMX group and 14.6% in the CC group. CONCLUSION(S): The overall rate
      of ovulation and pregnancy were similar with TMX and CC. TMX is a suitable
      alternative agent to CC in the management of anovulatory infertility.

PMID- 11334922
TI  - Birth of a healthy baby following vitrification of human blastocysts.
AB  - OBJECTIVE: To assess vitrification of human blastocysts. DESIGN: Retrospective
      study of blastocyst vitrification. SETTING: A private clinic. PATIENT(S): Twenty
      couples with different types of infertility. INTERVENTION(S): Blastocysts were
      frozen with rapid vitrification and then transferred after thawing. We vitrified
      blastocysts using a modification of Ishimori's vitrification solution of ethylene
      glycol and dimethyl sulfoxide (VSED). MAIN OUTCOME MEASURE(S): After thawing,
      survival was defined by the embryo's development morphology after 6 hours or
      overnight culture. RESULT(S): Eighteen of 20 patients underwent treatment. Of 45
      vitrified blastocysts, 36 survived, for a survival rate of 80% (36 of 45). The
      implantation rate was 21.9% (7 of 32), and the pregnancy rate (per embryo
      transfer cycle) was 33.3% (6 of 18). One of the pregnancies resulted in the
      delivery of a healthy baby. CONCLUSION(S): Supernumerary embryos were grown in
      culture to blastocysts, and the survival rate of vitrified-thawed blastocysts was
      the same as that for slow freezing of early stage embryos. Blastocyst
      vitrification should prove effective for clinical treatment. The present results
      strongly suggest that this rapid and successful vitrification procedure will
      replace conventional cryopreservation in the future.

PMID- 11334923
TI  - Heterotopic cervical pregnancy successfully treated with transvaginal ultrasound
      guided aspiration and cervical-stay sutures.
AB  - OBJECTIVE: To present a case of a heterotopic cervical pregnancy successfully
      treated with transvaginal ultrasound-guided aspiration and cervical-stay sutures.
      DESIGN: Case report. SETTING: Tertiary academic IVF program. PATIENT(S): A 35
      year-old woman who conceived from IVF-ET treatment at 5.5 weeks of gestation.
      INTERVENTION(S): Transvaginal ultrasound-guided aspiration of the cervical
      pregnancy followed by cervical-stay sutures to control hemorrhage after
      aspiration. MAIN OUTCOME MEASURE(S): Recovery of the patient, preservation of the
      intrauterine pregnancy, and sequelae. RESULTS(S): The cervical pregnancy was
      successfully aborted, and the intrauterine pregnancy progressed to term.
      CONCLUSION(S): Transvaginal ultrasound-guided aspiration in combination with
      hemostatic cervical-stay sutures can be safely used to manage heterotopic
      cervical pregnancies.

PMID- 11334924
TI  - Anonymous oocyte donation: a follow-up questionnaire.

PMID- 11334925
TI  - Insulin-like growth factors and their receptors in human fallopian tube in
      reproductive-age women.

PMID- 11334926
TI  - African trypanosomes in the 21st century: what is their future in science and in
      health?
AB  - The African trypanosomes remain well recognised for their role as an interesting
      model eukaryote for basic science, but are loosing ground in their ability to
      contribute to understanding common cellular mechanisms. At the same time, the
      diseases they cause remain as prevalent as ever, but appear increasingly
      irrelevant in their wider medical, social, economic and political context. What
      can be done to keep trypanosome biology relevant and vigorous in the 21st
      century?

PMID- 11334927
TI  - African trypanosomiasis research: 100 years of progress, but questions and
      problems still remain.
AB  - Past and present progress in our understanding of African trypanosomiasis is
      briefly reviewed. Although tremendous scientific strides have been achieved, an
      epidemic of the disease is currently underway. Three areas of research which are
      believed necessary for the control of African trypanosomiasis are discussed. It
      is suggested that a better understanding of the host-parasite relationship is
      essential; more emphasis and a broader approach to drug development is required;
      and finally, further research into the socio-economic aspects of African
      trypanosomiasis is urgently needed before the human disease can again be
      controlled.

PMID- 11334928
TI  - The biology of kinetoplastid parasites: insights and challenges from genomics and
      post-genomics.
AB  - Kinetoplastid parasites exhibit a rich and diverse biology which mirrors many of
      the most interesting topics of current interest and study in the broader
      biological sciences. These evolutionarily ancient organisms possess intriguing
      mechanisms for control of gene expression, and exhibit complex patterns of cell
      morphogenesis orchestrated by an internal cytoskeleton. Their cell shapes change
      during a set of complex cell type differentiations in their life cycles. These
      differentiations are intimately linked to interactions with mammalian hosts or
      insect vectors, and often, these differentiations appear central to the
      successful transfer of the parasite between vector and host, and host and vector.
      The basics of this rich and complex cell and life cycle biology were described
      (with often rather forgotten clarity and prescience) in the early period of the
      last century. The last 30 years have seen major developments in our understanding
      of this biology. Ultrastructural differences in the various cells of the life
      cycle stages of Trypanosoma brucei, Trypanosoma cruzi and the various Leishmania
      species have been documented, and such studies have proven highly informative in
      defining important aspects of parasite adaptation. They have also proven to be a
      rich source of information for defining unusual aspects of parasite cell biology,
      novel organelles and cell architecture. This ultrastructural cell biology has
      been mirrored in a set of biochemical explanations defining unusual aspects of
      metabolism, surface molecules, and organelles. Finally, the application of
      molecular biology to these parasites revealed fascinating layers of complexity in
      the control of gene expression. These molecular studies have given us particular
      insights into polycistronic transcription, trans-splicing, RNA editing and gene
      rearrangements during antigenic variation. In contrast to other microbial
      systems, these cell biological, biochemical and molecular studies have not been
      greatly aided by insights gained from genetics--the diploid nature of the genome
      has discouraged the application of selectional genetics, mutant isolation and
      analysis. This is an important fact, since in general, it means that we have only
      recently started to analyse the phenotypes of mutants produced in the context of
      reverse genetics. In the following, I will argue that this lack of investment in
      the analysis of mutant phenotype is just one of the challenges that will need to
      be met if we are to gain the expected added value from the parasite genome
      projects. In this presentation, I will use some of the current areas of interest
      in the biology of T. brucei, T. cruzi and the Leishmania species to rehearse some
      of the insights and challenges that are likely to stem from the application of
      genomics and post-genomic studies to the kinetoplastid parasites. In some cases,
      I will exemplify points by illustrations from my laboratory's work, interests and
      hypotheses. The presentation slants therefore towards T. brucei biology, however,
      in each case the reader will, no doubt, see the generalities of application to
      other kinetoplastid parasites.

PMID- 11334929
TI  - Replication of kinetoplast DNA: an update for the new millennium.
AB  - In this review we will describe the replication of kinetoplast DNA, a subject
      that our lab has studied for many years. Our knowledge of kinetoplast DNA
      replication has depended mostly upon the investigation of the biochemical
      properties and intramitochondrial localisation of replication proteins and
      enzymes as well as a study of the structure and dynamics of kinetoplast DNA
      replication intermediates. We will first review the properties of the
      characterised kinetoplast DNA replication proteins and then describe our current
      model for kinetoplast DNA replication.

PMID- 11334930
TI  - Phloem-restricted trypanosomatids form a clearly characterised monophyletic group
      among trypanosomatids isolated from plants.
AB  - Although only one genus name has been proposed as yet for all plant trypanosomes,
      'Phytomonas', it is clear that they can differ from one another in terms of both
      their biological properties and their effects. Recent serological and molecular
      studies have confirmed the substantial heterogeneity of these trypanosomatids,
      which the use of a single genus name does not even hint at. We set out to show in
      this paper that there is at least one homogeneous group of plant trypanosomes
      that can be defined explicitly by a single genus and species name and that
      differs substantially from all the other clusters that may be identified by one
      technique or another: the phloem-restricted trypanosomatids found in Latin
      America.

PMID- 11334931
TI  - The surface structure of trypanosomes in relation to their molecular phylogeny.
AB  - Molecular phylogenetic analysis using genes coding for ribosomal RNA and proteins
      suggests that trypanosomes are monophyletic. Salivarian trypanosomes showing
      antigenic variation of the variant surface glycoprotein (VSG) diverged from non
      Salivarian trypanosomes some 200-300 million years ago. Representatives of the
      non-Salivarian group, the mammalian parasite, Trypanosoma cruzi, and the fresh
      water fish trypanosome, T. carassii, are characterised by surfaces dominated by
      carbohydrate-rich mucin-like glycoproteins, which are not subject to antigenetic
      variation. It is suggested that this latter surface structure is typical for non
      Salivarian trypanosomes as well as members of the other Kinetoplastid suborder,
      the Bodonina. This would imply that at some point in time in the evolution of the
      Salivaria the highly abundant and comparatively poorly immunogenetic mucin-like
      molecules must have been replaced for equally abundant but highly immunogenic VSG
      like molecules. While the selective advantage for such a unique transition is
      difficult to imagine, the subsequent diversification of VSG genes/molecules may
      have been comparatively straightforward because even the most limited form of
      antigenic variation would have extended the duration of infection in the
      vertebrate and thus would have increased the chance for transfer to the vector.

PMID- 11334932
TI  - The life cycle of Trypanosoma cruzi revisited.
AB  - The basic features of the life cycle of Trypanosoma cruzi have been known for
      nearly a century. Various aspects of the life cycle, however, have been
      elucidated only recently, whilst others remain either controversial or unstudied.
      Here, we present a revised life cycle influenced by recent findings and specific
      questions that remain unresolved.

PMID- 11334933
TI  - Enzymes of carbohydrate metabolism as potential drug targets.
AB  - The potential for chemotherapeutic exploitation of carbohydrate metabolism in the
      Trypanosomatidae is reviewed. This review is based largely on discussions held at
      a meeting of the COST B9 Action, entitled 'Bioenergetics of Protozoan Parasites'.
      The major questions posed were: which enzymes are the best to target; what
      further information is required to allow their use for rational drug development;
      what compounds would constitute the best inhibitors and which of the enzymes of
      the pentose-phosphate pathway are present inside the glycosomes, as well? Only
      partial answers could be obtained in many cases, but the interactive discussion
      between the multidisciplinary group of participants, comprising chemists,
      biochemists and molecular biologists, provided thought-provoking ideas and will
      help direct future research.

PMID- 11334934
TI  - cAMP signalling in Trypanosoma brucei.
AB  - Cyclic AMP was the first second messenger to be identified. After five decades of
      research, much is currently known about its biological functions and clinical
      implications. Several components of the cAMP signalling pathways, such as the G
      protein coupled receptors and the phosphodiesterases, have become sensitive and
      specific drug targets for a host of clinical applications. Surprisingly, very
      little effort has been invested so far into the study of cAMP signalling in
      parasites, and its significance in host/parasite interaction. Our laboratory has
      embarked on a study of cAMP signalling in Trypanosoma brucei. A newly identified
      adenylyl cyclase, GRESAG4.4B, a member of a small family of closely related
      genes, is being used as a model molecule for investigating the mechanisms which
      control cyclase activity in the T. brucei cell. On the other hand, a number of
      genes for different families of cAMP-specific phosphodiesterases have been
      identified and characterised. One enzyme, TbPDE1, is coded for by a single-copy
      gene. Knock-outs of this gene display an almost normal phenotype in culture,
      indicating that TbPDE1 is not an essential enzyme under culture conditions. A
      second phosphodiesterase which is being studied in detail, TbPDE2A, is clearly
      different from TbPDE1, and it is coded for by a member of a small gene family
      containing about six similar, but non-identical genes. TbPDE2A, as TbPDE1, is
      specific for cAMP. In its N-terminal, it contains a GAF domain which may
      represent an allosteric cGMP-binding site. The other members of the TbPDE2 family
      all exhibit strongly conserved catalytic domains, but vary widely in their N
      terminal regulatory domains. With regard to downstream signalling by the cAMP
      generated through the interplay of adenylyl cyclases and phosphodiesterases, we
      have recently identified a single-copy gene (TbRSU1) which codes for a putative
      regulatory subunit of the cAMP-regulated protein kinase A. This protein exhibits
      considerable similarity with its mammalian counterparts. Immunoprecipitation co
      precipitates a protein kinase activity with the characteristics of protein kinase
      A.

PMID- 11334935
TI  - The role of endothelin in the pathogenesis of Chagas' disease.
AB  - Infection with Trypanosoma cruzi causes a generalised vasculitis of several
      vascular beds. This vasculopathy is manifested by vasospasm, reduced blood flow,
      focal ischaemia, platelet thrombi, increased platelet aggregation and elevated
      plasma levels of thromboxane A(2) and endothelin-1. In the myocardium of infected
      mice, myonecrosis and a vasculitis of the aorta, coronary artery, smaller
      myocardial vessels and the endocardial endothelium are observed.
      Immunohistochemistry studies employing anti-endothelin-1 antibody revealed
      increased expression of endothelin-1, most intense in the endocardial and
      vascular endothelium. Elevated levels of mRNA for prepro endothelin-1, endothelin
      converting enzyme and endothelin-1 were observed in the infected myocardium. When
      T. cruzi-infected mice were treated with phosphoramidon, an inhibitor of
      endothelin converting enzyme, there was a decrease in heart size and severity of
      pathology. Mitogen-activated protein kinases and the transcription factor
      activator-protein-1 regulate the expression of endothelin-1. Therefore, we
      examined the activation of mitogen-activated protein kinases in the myocardium by
      T. cruzi. Western blot demonstrated an extracellular signal regulated kinase. In
      addition, the activator-protein-1 DNA binding activity, as determined by
      electrophoretic mobility shift assay, was increased. Increased expression of
      cyclins A and cyclin D1 was observed in the myocardium, and immunohistochemistry
      studies revealed that interstitial cells and vascular and endocardial endothelial
      cells stained intensely with antibodies to these cyclins. These data demonstrate
      that T. cruzi infection of the myocardium activates extracellular signal
      regulated kinase, activator-protein-1, endothelin-1, and cyclins. The activation
      of these pathways is likely to contribute to the pathogenesis of chagasic heart
      disease. These experimental observations suggest that the vasculature plays a
      role in the pathogenesis of chagasic cardiomyopathy. Additionally, the
      identification of these pathways provides possible targets for therapeutic
      interventions to ameliorate or prevent the development of cardiomyopathy during
      T. cruzi infection.

PMID- 11334936
TI  - Transporters in African trypanosomes: role in drug action and resistance.
AB  - Sleeping sickness is an increasing problem in many parts of sub-Saharan Africa.
      The problems are compounded by the lack of new medication, and the increasing
      resistance against traditional drugs such as melarsoprol, berenil and
      isometamidium. Over the last few years, much progress has been made in
      understanding how drug action, and the development of resistance, is related to
      the mechanisms by which the parasite ingests the drugs. In some cases novel
      transporters have been identified. In other cases, transporters do not appear to
      be involved in drug uptake, and selectivity must lie with other parasite
      features, such as a specific target or activation of the drug. Lessons learned
      from studying the uptake of drugs currently in use may assist the design of a
      much needed new generation of trypanocides.

PMID- 11334937
TI  - Control and function of the bloodstream variant surface glycoprotein expression
      sites in Trypanosoma brucei.
AB  - African trypanosomes escape the host immune response through a periodical change
      of their surface coat made of one major type of protein, the variant surface
      glycoprotein. From a repertoire of a thousand variant surface glycoprotein genes
      available, only one is expressed at a time, and this takes place in a specialised
      expression site itself selected from a collection of an estimated 20-30 sites. As
      the specialised expression sites are long polycistronic transcription units, the
      variant surface glycoprotein is co-transcribed with several other genes termed
      expression site-associated genes. How do the trypanosomes only use a single
      specialised expression site at a time? Why are there two dozen specialised
      expression sites? What are the functions of the other genes of these
      transcription units? We review the currently available answers to these
      questions.

PMID- 11334938
TI  - Parasite genome initiatives.
AB  - During 1993-1994, scientists from developing and developed countries planned and
      initiated a number of parasite genome projects and several consortiums for the
      mapping and sequencing of these medium-sized genomes were established, often
      based on already ongoing scientific collaborations. Financial and other support
      came from WHO/TDR, Wellcome Trust and other funding agencies. Thus, the genomes
      of Plasmodium falciparum, Schistosoma mansoni, Trypanosoma cruzi, Leishmania
      major, Trypanosoma brucei, Brugia malayi and other pathogenic nematodes are now
      under study. From an initial phase of network formation, mapping efforts and
      resource building (EST, GSS, phage, cosmid, BAC and YAC library constructions),
      sequencing was initiated in gene discovery projects but soon also on a small
      chromosome, and now on a fully fledged genome scale. Proteomics, functional
      analysis, genetic manipulation and microarray analysis are ongoing to different
      degrees in the respective genome initiatives, and as the funding for the whole
      genome sequencing becomes secured, most of the participating laboratories, apart
      from larger sequencing centres, become oriented to post-genomics. Bioinformatics
      networks are being expanded, including in developing countries, for data mining,
      annotation and in-depth analysis.

PMID- 11334939
TI  - Cellular trafficking in trypanosomatids: a new target for therapies?
AB  - Pathogenic trypanosomatids cause a plethora of diseases marked by the lack of
      efficient vaccines and therapies. As a consequence, studies are being conducted
      that are geared towards the understanding of basic mechanisms and various
      biological aspects of these parasites that might be used as targets for new
      developments in these areas. One such aspect is the understanding of specific
      cellular trafficking mechanisms that might be attacked with the intention of
      disease control. In this paper, we give an overview of our current knowledge of
      cellular targeting mechanisms in trypanosomatids, with special emphasis on our
      data related to lysosomal targeting of cysteine proteinases in Leishmania.

PMID- 11334940
TI  - The Leptomonas seymouri spliced leader RNA promoter requires a novel
      transcription factor.
AB  - The spliced leader RNA gene promoter in Leptomonas seymouri requires three
      promoter elements for efficient and accurate transcription of the spliced leader
      RNA. The upstream most element appears to have a functional homolog in Leishmania
      species and in the African trypanosomes. The protein factor, promoter binding
      protein-1, interacts with the upstream element and appears to function as a basal
      transcription factor. Promoter binding protein-1 has three subunits; 36, 41 and
      57 kDa. Using microsequencing techniques, we have obtained peptide sequence from
      each subunit. These data have enabled us to recently identify the Leptomonas gene
      that encodes the 41 kDa subunit. The 41 kDa subunit, comprised of 381 amino
      acids, is a founding member of a new class of transcription factors since
      extensive database searches revealed no homology to any known protein. This
      subunit, encoded by a single copy gene, has a potential nuclear localisation
      signal at amino acid positions 71-76. There are also multiple dileucine repeats
      with unknown function. Anti-41 kDa protein polyclonal antibodies are being
      employed to test the function of the 41 kDa subunit in PBP-1 activities.

PMID- 11334941
TI  - Parasite persistence in the aetiology of Chagas disease.
AB  - Two primary hypotheses are proposed to account for pathogenesis in chronic
      Trypanosoma cruzi infections: that the persistence of T. cruzi at specific sites
      in the infected host results in chronic inflammatory reactivity and that T. cruzi
      infection induces immune responses which are targetted at self tissues. The data
      supporting parasite persistence as the primary cause of disease in T. cruzi
      infection have been recently reviewed and the reader is referred to this review
      for extensive documentation of most of the arguments outlined herein. This
      manuscript will briefly reiterate the main points of this previous review, adding
      additional data that have been presented since its publication. Then,
      philosophical and practical arguments on why Chagas disease should be
      investigated and treated as a parasitic infection and not as an autoimmune
      disease are presented. This is admittedly an 'opinion piece' and not a balanced
      review of the literature on Chagas disease. There are substantial data other than
      those reviewed here, which have been presented in support of the autoimmunity
      hypothesis. It is left to others to review that body of literature.

PMID- 11334942
TI  - Autoimmunity in Chagas heart disease.
AB  - The possibility that cardiac autoimmunity contributes to the pathogenesis of
      Chagas heart disease is controversial. In this paper, we address the following
      questions regarding the genesis of autoimmunity in Chagas heart disease: (i) What
      mechanism(s) are potentially responsible for the generation of self-directed
      antibodies and lymphocytes? (ii) What is the evidence that any of these
      mechanisms actually can occur? (iii) What are the implications of the presence of
      autoimmunity for other mechanisms of cardiac inflammation?

PMID- 11334943
TI  - Innate and acquired control of trypanosome parasitaemia in Cape buffalo.
AB  - The review discusses the roles of serum xanthine oxidase, serum catalase and
      trypanosome-specific immune responses in the regulation of the level of
      trypanosome parasitaemic waves in Cape buffalo.

PMID- 11334944
TI  - Cryptobiosis and its control in North American fishes.
AB  - Cryptobiosis is caused by the haemoflagellates Cryptobia bullocki and Cryptobia
      salmositica. These parasites infect food fishes (e.g. flounders, salmon) on both
      the Atlantic and Pacific coasts of North America and clinical signs of the
      disease include anaemia, and abdominal distention with ascites. The virulent
      factor in salmonid cryptobiosis, caused by C. salmositica, is a secretory
      metalloprotease (200 kDa). Fish mortality may be up to 100% in the absence of
      treatment, consequently strategies have been developed to protect them from
      disease/mortality. A single dose of a live vaccine protects fish for at least 2
      years, and it is via the production of complement-fixing antibodies, enhanced
      phagocytosis and cell-mediated cytotoxicity. Inhibition of the parasite's
      cysteine protease by a monoclonal antibody reduces multiplication, infectivity
      and survival of the parasite. Consequently, the recombinant cysteine protease (49
      kDa) of the parasite will be tested as a potential vaccine. The trypanocidal
      drug, isometamidium chloride (1.0 mg/kg), is effective (therapeutic and
      prophylactic) against C. salmositica in chinook salmon. Its efficacy is
      significantly enhanced if it is conjugated either to a monoclonal antibody or to
      polyclonal antibodies from immune fish. Selective breeding of Cryptobia-resistant
      brook charr (innate resistance to infection) is possible, and the resistant
      factor(s) is controlled by a dominant Mendelian locus. In these resistant charr
      the parasite is lysed via the alternate pathway of complement activation (innate
      immunity to infection). There are also Cryptobia-tolerant charr, fish that are
      susceptible to infection but have no clinical disease (innate resistance to
      disease). In these fish, one of the natural anti-proteases, alpha2-macroglobulin,
      neutralises the metalloprotease secreted by C. salmositica. Production of
      transgenic Cryptobia-tolerant salmon is an option to vaccination and or
      chemotherapy. Also, transgenic pathogen-tolerant animals may be an alternate
      strategy against other pathogens where the disease mechanism is similar to
      cryptobiosis.

PMID- 11334945
TI  - Alternative versus classical macrophage activation during experimental African
      trypanosomosis.
AB  - African trypanosomes are extracellular parasites causing sleeping sickness to
      human or nagana to livestock in sub-Saharan Africa. To gain insight into factors
      governing resistance/susceptibility to these parasites, the immune responses in
      mice infected with a Trypanosoma brucei phospholipase C null mutant (PLC(-/-)) or
      its wild type counterpart (WT) were compared. We found that the T. b. brucei
      mutant inducing a chronic infection triggers the production of type I cytokines
      during the early stage of infection, followed by the secretion of type II
      cytokines in the late/chronic phase of the disease. In contrast, WT-infected mice
      are killed within 5 weeks and remain locked in a type I cytokine response. The
      type I/type II cytokine balance may influence the development of different
      subsets of suppressive macrophages, i.e. classically activated macrophages (type
      I) versus alternatively activated macrophages (type II) that are antagonistically
      regulated. Therefore, the phenotype and accessory cell function of macrophages
      elicited during WT and PLC(-/-) T. b. brucei infections were addressed. Results
      indicate that classically activated macrophages develop in a type I cytokine
      environment in the early phase of both WT and PLC(-/-) trypanosome infections. In
      the late stage of infection, only PLC(-/-)-infected mice resisting the infection
      develop type II cytokine-associated alternative macrophages. In parallel, we
      found that mice susceptible to Trypanosoma congolense infection, showing an
      exponential parasite growth until they die, have a higher level of type II
      cytokines in the early stage of infection than resistant animals controlling the
      first peak of parasitaemia. The levels of type I cytokines were comparable in
      both T. congolense-resistant and -susceptible mice. On the basis of these
      results, we propose that survival to African trypanosome infection requires a
      type I cytokine environment and classical macrophage activation in the early
      stage of infection, enabling mice to control the first peak of parasitaemia.
      Thereafter, a switch to type II cytokine environment triggering alternative
      macrophage activation is required to enable progression of the disease into the
      chronic phase. The possible role of the sequential activation of alternative
      macrophages in the late/chronic stage of infection in the increased resistance of
      mice to PLC(-/-) T. b. brucei will be discussed.

PMID- 11334946
TI  - Parasite polyclonal activators: new targets for vaccination approaches?
AB  - Taking into consideration that the immune response following infection promotes
      the expansion of lymphocyte clones that are essentially non-specific, ensuring
      both parasite evasion and persistence inside the host, what would be the major
      consequences of this polyclonal response to the development of immunopathology?
      We favor the hypothesis that the polyclonal B cell responses triggered by the
      infection is responsible of the host susceptibility and is a major contributor to
      the maintenance of a progressive disease. In particular, the activation of B
      cells by parasite mitogens would contribute to the class determination of T cell
      responses and to the inhibition of macrophages - target cells for parasite
      multiplication and also responsible for parasite clearance. We also envisage that
      the activation of T cells by parasite 'superantigens', and the ensuing energy and
      deletion of these cells, processes that are frequently observed, would contribute
      for the immunosuppression as well as to parasite escape and persistence in the
      host. We had concentrated our efforts on the study of the non-specific aspects of
      the immune response following Trypanosoma cruzi infection. We aimed at finding
      new strategies to modulate and control the mechanisms leading to both the
      immunosuppression and the development of chronic auto-immunity leading to
      rational vaccine approaches against parasite infection and immunopathology.

PMID- 11334947
TI  - Some general aspects of the distribution and epidemiology of bovine
      trypanosomosis in southern Africa.
AB  - Bovine trypanosomosis occurs in vast areas of southern Africa. Its epidemiology
      and impact on cattle production is determined largely by the level of interaction
      between tsetse and cattle. Four situations can be distinguished. First, areas
      where cattle are absent. Second, zones where cattle have been introduced in game
      areas but where game is still abundant and constitutes the major source of food
      for tsetse. Third, areas where, often because of human interference, the density
      of game animals is low and cattle constitute the main source of food and finally,
      areas where cattle occur at the edge of tsetse-infested zones. In southern
      Africa, the impact of the disease on cattle production varies according to the
      epidemiological circumstances. The disease has an epidemic character with
      significant impacts on production in areas where cattle have been introduced
      recently or along the interface between tsetse-infested game areas and tsetse
      free cultivated areas. Bovine trypanosomosis has an endemic character, with
      little impact on production, in areas where tsetse mainly feed on cattle and
      where the invasion of tsetse is low. Options for the control of bovine
      trypanosomosis will vary according to the epidemiological circumstance. In
      particular, the control of tsetse with insecticide-treated cattle will only be
      effective when a large proportion of feeds are taken from cattle over a large
      area and when the invasion of tsetse can be reduced sufficiently.

PMID- 11334948
TI  - Use of mobile genetic elements as tools for molecular epidemiology.
AB  - Trypanosomiasis is a complex zoonotic disease where human-infective and non-human
      infective strains of Trypanosoma brucei interact in the same transmission cycles.
      Differentiating these strains is paramount to understanding disease epidemiology.
      Restriction fragment length polymorphism analysis of repetitive DNA has provided
      such a method for distinguishing human and non-human isolates. Unfortunately,
      this approach requires large amounts of material and a more rapid approach is
      required. We have developed a novel technique, mobile genetic element-PCR, for
      assaying for positional variation of the mobile genetic element, RIME. The
      trypanosome genome contains up to 400 copies of RIME. Using this approach we have
      observed considerable variation between strains of T. brucei. Such a technique
      may offer potential as a method for differentiating non-human- and human
      infective trypanosomes and shows promise as a rapid sensitive tool for
      investigating the epidemiology of sleeping sickness.

PMID- 11334949
TI  - Comparing apples and oranges--model-based assessment of different tsetse
      transmitted trypanosomosis control strategies.
AB  - The current control strategies for tsetse-transmitted trypanosomosis in cattle
      (trypanocidal drugs, tsetse control and trypanotolerant cattle) are briefly
      reviewed and their adoption rates in different geographic regions of sub-Saharan
      Africa are presented. The impact of these control strategies and the potential
      use of vaccines, should they be developed, on trypanosomosis transmission were
      compared using a mathematical model. The relative trypanosomosis prevalence
      compared with no control was estimated across a range of control coverages (from
      none to complete control coverage) by varying the change in specific model
      parameters influenced by individual control measures. Based on this comparison,
      the relative rankings of the effect of control strategies on reducing disease
      prevalence were: vector control, vaccination, and drug use, in that order. In
      this model, trypanotolerance was assumed to decrease disease prevalence, but not
      to influence transmission. Differences in the predicted impact of control
      measures on the transmission of human sleeping sickness are discussed. Finally,
      the role of transmission model outputs as inputs for economic models to guide
      investment decisions for trypanosomosis control is emphasised.

PMID- 11334950
TI  - Detection and identification of Trypanosoma of African livestock through a single
      PCR based on internal transcribed spacer 1 of rDNA.
AB  - Primers hybridising with the rDNA cistron have previously been evaluated for PCR
      diagnosis specific for kinetoplastids, and shown to detect and differentiate the
      Trypanosoma brucei complex and Trypanosoma cruzi. Kin1 and Kin2 primers,
      amplifying internal transcribed spacer 1, were subsequently evaluated for the
      diagnosis of African livestock trypanosomosis. Based on the size of the PCR
      products obtained, Kin primers allowed detection and identification of three
      Trypanosoma congolense types (savannah, forest and Kenya Coast), with distinction
      among themselves and from the subgenus Trypanozoon (T. brucei spp., Trypanosoma
      evansi and Trypanosoma equiperdum), Trypanosoma vivax, Trypanosoma simiae and
      Trypanosoma theileri. These primers were shown to be suitable for the sensitive
      and type-specific diagnosis of African livestock trypanosome isolates through a
      single PCR even in the case of multi-taxa samples. With field samples (buffy-coat
      from cattle blood) sensitivity was close to the sensitivity observed in single
      reactions with the classical specific primers for the Trypanozoon subgenus and T.
      congolense-type savannah, but was lower for detection of T. vivax. Additional
      reaction, improvement of DNA preparation, and/or new primers design are necessary
      to improve the sensitivity for detection of T. vivax in field samples. However,
      these primers are suitable for isolate typing through a single PCR.

PMID- 11334951
TI  - Trypanosomiasis control.
AB  - In July 2000, Heads of State of the 36th Session of the Organisation for African
      Unity signed a potentially important declaration on African trypanosomiasis,
      urging member states "to act collectively to rise to the challenge of eliminating
      the problem through concerted efforts in mobilising the necessary human,
      financial and material resources required to render Africa tsetse-free within the
      shortest time possible". To many, such an ambitious dream is received with some
      scepticism, recalling the doubts that surrounded a similar declaration signed in
      Brasilia in 1991, which paved the way for the Southern Cone Initiative against
      American trypanosomiasis (Chagas disease). True, the two diseases are quite
      different. But the operational challenges are quite similar, and there are
      sufficient biological parallels to suggest that the Latin American experience in
      controlling Chagas disease may provide a useful model for the control of African
      trypanosomiasis.

PMID- 11334952
TI  - Bacterial symbiosis and paratransgenic control of vector-borne Chagas disease.
AB  - The triatomine vectors of Chagas disease are obligate haematophagous insects,
      feeding on vertebrate blood throughout their entire developmental cycle. As a
      result of obtaining their nutrition from a single food source, their diet is
      devoid of certain vitamins and nutrients. Consequently, these insects harbour
      populations of bacterial symbionts within their intestinal tract, which provide
      the required nutrients that are lacking from their diet. We have isolated and
      characterised symbiont cultures from various triatomine species and developed a
      method for genetically transforming them. We can then reintroduce them into their
      original host species, thereby producing stable paratransgenic insects in which
      we are able to express heterologous gene products. Using this methodology, we
      have generated paratransgenic Rhodnius prolixus that are refractory for infection
      with Trypanosoma cruzi. Two examples of potentially refractory genes are
      currently being expressed in paratransgenic insects. These include the insect
      immune peptide cecropin A and active single chain antibody fragments. We have
      also developed an approach that would allow introduction of genetically modified
      bacterial symbionts into natural populations of Chagas disease vectors. This
      approach utilises the coprophagic behaviour of these insects, which is the way in
      which the symbionts are transmitted among bug populations in nature. The
      production and ultimate release of transgenic or paratransgenic insects for
      public health applications is potentially very promising but also worthy of much
      careful consideration with respect to environmental, political, and human safety
      concerns.

PMID- 11334953
TI  - The endosymbionts of tsetse flies: manipulating host-parasite interactions.
AB  - Through understanding the mechanisms by which tsetse endosymbionts potentiate
      trypanosome susceptibility in tsetse, it may be possible to engineer modified
      endosymbionts which, when introduced into tsetse, render these insects incapable
      of transmitting parasites. In this study we have assayed the effect of three
      different antibiotics on the endosymbiotic microflora of tsetse (Glossina
      morsitans morsitans). We showed that the broad-spectrum antibiotics, ampicillin
      and tetracycline, have a dramatic impact on tsetse fecundity and pupal emergence,
      effectively rendering these insects sterile. This results from the loss of the
      tsetse primary endosymbiont, Wigglesworthia glossinidia, which is eradicated by
      ampicillin and tetracycline treatment. Using the sugar analogue and antibiotic,
      streptozotocin, we demonstrated specific elimination of the tsetse secondary
      endosymbiont, Sodalis glossinidius, with no observed detrimental effect upon W.
      glossinidia. The specific eradication of S. glossinidius had a negligible effect
      upon the reproductive capability of tsetse but did effect a significant reduction
      in fly longevity. Furthermore, elimination of S. glossinidius resulted in
      increased refractoriness to trypanosome infection in tsetse, providing further
      evidence that S. glossinidius plays an important role in potentiating trypanosome
      susceptibility in this important disease vector. In the light of these findings,
      we highlight progress made towards developing recombinant Sodalis strains
      engineered to avoid potentiating trypanosome susceptibility in tsetse. In
      particular, we focus on the chitinase/N-acetyl-D-glucosamine catabolic machinery
      of Sodalis which has previously been implicated in causing immune inhibition in
      tsetse.

PMID- 11334954
TI  - Differential susceptibility of triatomines of the genus Rhodnius to Trypanosoma
      rangeli strains from different geographical origins.
AB  - The susceptibility of four Rhodnius species to different Trypanosoma rangeli
      strains was evaluated using both intracoelomic inoculation and oral infection.
      Rhodnius prolixus, Rhodnius domesticus, Rhodnius neglectus and Rhodnius nasutus
      were infected with Trypanosoma rangeli Macias (Venezuela), Choachi (Colombia) and
      SC-58 (Brazil) strains, revealing distinct haemolymph and salivary glands
      infection rates. The obtained infection rates were revealed to be dependent on
      the method of infection and the triatomine species. Our results suggest the
      existence of a high adaptation between the strain and the local vector.

PMID- 11334955
TI  - New molecular markers for phlebotomine sand flies.
AB  - Using degenerate-primers PCR we isolated and sequenced fragments from the sand
      fly Lutzomyia longipalpis homologous to two behavioural genes in Drosophila,
      cacophony and period. In addition we identified a number of other gene fragments
      that show homology to genes previously cloned in Drosophila. A codon usage table
      for L. longipalpis based on these and other genes was calculated. These new
      molecular markers will be useful in population genetics and evolutionary studies
      in phlebotomine sand flies and in establishing a preliminary genetic map in these
      important leishmaniasis vectors.

PMID- 11334956
TI  - Some current problems in the systematics of Trypanosomatids.
AB  - Trypanosomatids have been traditionally allocated to a number of genera that were
      described based on morphological features and host range. Recently molecular
      studies have provided new data that has allowed a reexamination of the genera.
      While in some cases the molecular data has been in agreement with the
      morphological characters they have also reinforced existing doubts about some
      current generic divisions as well as raising new concerns. A revision of the
      trypanosomatid genera is required. Suggested features of such a revision would
      include: (1) The possible division of Trypanosoma into new genera to reflect the
      wide genetic diversity of this group; (2) The inclusion of Leishmania,
      Sauroleishmania and Endotrypanum within a single genus given their high genetic
      affinity; (3) The complete revision of the monogenetic typanosomatid genera to
      reflect monophyletic groups; (4) A more precise redescription of Phytomonas so as
      to only include the monophyletic plant flagellates.

PMID- 11334957
TI  - Sex and evolution in trypanosomes.
AB  - Trypanosoma brucei is still the only kinetoplastid known to undergo genetic
      exchange, but it seems unreasonable to suppose that it evolved this process all
      by itself. The position of T. brucei on a molecular phylogenetic tree constructed
      from 18S ribosomal RNA gene sequences offers no clues to the likely existence of
      genetic exchange in trypanosome species other than the Salivaria, because this
      group of trypanosomes appears to have diverged from the rest a very long time
      ago. Antigenic variation is one characteristic shared by the Salivaria, which has
      been particularly well-studied in T. brucei. The large proportion of the genome
      devoted to variant antigen genes and related sequences in T. brucei, suggests a
      possible role for genetic exchange in enhancing the diversity of the repertoire.
      Alternatively, genetic exchange may counter potential excessive double-strand DNA
      damage brought about by the DNA rearrangements associated with antigenic
      variation. The remarkable biparental inheritance of organelle DNA (=kinetoplast
      DNA) in T. brucei is without precedent in other eukaryotes. The result of genetic
      exchange is to enhance the heterogeneity of the kinetoplast DNA minicircles.

PMID- 11334958
TI  - The more insect trypanosomatids under study-the more diverse Trypanosomatidae
      appears.
AB  - From 10 trypanosomatids genera six comprise monogenetic parasites of insects and
      for the rest of four genera insects may serve as vectors. The invertebrate host
      is an essential element of trypanosomatids life cycle, but from more than 900
      recognised vertebrate hosts only about 500 species of insects have been
      discovered to be the hosts of homoxenous trypanosomatids. Nothing or very little
      is known about insect trypanosomatids in many extensive areas such as South East
      Asia, Australia, Japan and some others. Each new region explored brings many new
      findings. Recently flagellates were found in new insect species and families. The
      border of parasites distribution was expanded till Central Asia, Far East and
      North over the Polar Circle. As paleogeographical events are now under
      contemplating in trypanosomatids phylogeny researches so northern insect
      trypanosomatids may attract some attention as the elements of postglacial fauna
      which is definitely young. Very broad host specificity of insect trypanosomatids
      and high probability to isolate non-specific parasite show causes that only the
      investigation of a culture may solve the question 'what parasite was really
      isolated?'. Examination of cell morphotypes in the host has clearly demonstrated
      that they are not sufficient for classification and may lead us to be mistaken.
      The number of insect trypanosomatid cultures is inadequate for characterisation
      of the diversity of insects trypanosomatids. Trypanosoma is actually the only
      trypanosomatid genus which is out of questions. Insect trypanosomatids comprise
      the most diversified part of trypanosomatids evolutionary tree. Recent ssrRNA
      phylogenetic analysis and morphological data show that three insect isolates
      represent new lineages on trypanosomatid evolutionary tree, as well as
      dendrograms derived from PCR data demonstrated some new groups of isolates.
      Therefore, the more insect trypanosomatids are involved in laboratory
      investigations--the more new clusters or/and new lineages are appearing on the
      tree.

PMID- 11334959
TI  - Proceedings of the Third Internet Conference on Salivarian Trypanosomes and
      Trypanosomatids.

PMID- 11334960
TI  - Inhibition of human NK cell-mediated cytotoxicity by exposure to ammonium
      chloride.
AB  - Ammonium-chloride-containing solutions (AC) are routinely used to lyse red blood
      cells during preparation of PBMC. Although exposure to AC has been described to
      affect the ultrastructural appearance of large granular lymphocytes and to
      temporarily inhibit cytolytic activity of PBMC preparations, the cellular basis
      of this phenomenon has not been studied. Here, the inhibitory effect of AC on
      human CTL and NK-mediated cytotoxicity has been analyzed in 4-h 51Cr-release
      assays. The results show that NK killing of K562 leukemia cells and xenogeneic
      endothelial cells is inhibited by AC exposure. The effect is dose-dependent and
      reversible, because recovery of cytotoxicity is observed within 15 h of re
      culturing. AC does not reduce the viability of NK cells and the inhibitory effect
      is not mediated by the exhaustive release of granzymes upon AC treatment. In
      contrast, antigen-specific CTL killing of EBV-transformed B-lymphoblastoid cell
      lines and xenogeneic PHA lymphoblasts was less sensitive to AC and data are
      presented suggesting that FasL-induced apoptosis is not inhibited by AC. In
      conclusion, perforin-mediated NK killing is AC-sensitive whereas CTL killing and
      FasL-mediated killing appear to be AC-resistant. Therefore, AC represents a
      powerful tool to study different mechanisms of cell-mediated cytotoxicity and may
      be helpful in assessing antigen-specific CTL cytotoxicity without the influence
      of NK cell-mediated background killing.

PMID- 11334961
TI  - Isolation and characterization of rhesus blood dendritic cells using flow
      cytometry.
AB  - Recognition of dendritic cells (DCs) as initiators and modulators of immune
      responses and growing use of rhesus monkeys for the preclinical optimization of
      vaccine formulations prompted characterization of the phenotype and function of
      isolated rhesus peripheral blood DCs. We developed a flow cytometric method to
      directly identify and isolate DCs from rhesus peripheral blood whereby a T cell
      depleted population negative for CD3, CD14, CD16 and CD20 but positive for CD83
      yielded a cell population with surface markers, morphology, and a cytokine
      profile similar to human myeloid DCs. Rhesus blood DCs were more effective than
      monocytes and B cells in mixed lymphocyte reactions and in the presentation of
      recombinant malaria blood stage antigen MSP-1((42)) to autologous T cells. The
      ability to isolate rhesus blood DC from peripheral blood should be a useful tool
      for immunological investigations.

PMID- 11334962
TI  - Development of an ELISA to measure soluble CD163 in biological fluids.
AB  - CD163 is a monocyte/macrophage restricted transmembrane glycoprotein and a member
      of the scavenger receptor cysteine-rich (SRCR) family of proteins. SRCR proteins
      are typically associated with the immune system. The regulation of CD163 by
      cytokines and glucocorticoids suggests that it plays a role in inflammatory
      processes. While CD163 is expressed as a membrane-bound protein, it has been
      shown to be actively shed from the surface of monocytes in a protease-dependent
      fashion when cells are stimulated with a phorbol ester. To better elucidate the
      function and biological importance of CD163, we have developed a solid-phase
      sandwich enzyme linked immunosorbant assay (ELISA) for the detection of soluble
      CD163 in biological fluids. This assay has good repeatability both within and
      between runs (coefficients of variation (CVs) of 3.2% and 7.1% or better,
      respectively). While detection of CD163 was inhibited by ethylenediamine
      tetraacetic acid (EDTA), CD163 immunoreactivity was not altered by the addition
      of heparin or hemoglobin. This report details the development of this novel assay
      for soluble CD163 and provides the first evidence of CD163 immunoreactivity in
      normal plasma and serum samples.

PMID- 11334963
TI  - Flow cytometry-based phagocytosis assay for sensitive detection of opsonic
      activity of pneumococcal capsular polysaccharide antibodies in human sera.
AB  - The development of efficient vaccines against Streptococcus pneumoniae is of
      major importance for public health. The efficacy of pneumococcal vaccination and
      induced protection are thought to be reflected by the opsonic antibody titers in
      sera from vaccines. We describe a novel two-color flow cytometry technique for
      quantification of antibody-mediated pneumococcal phagocytosis. Serum-opsonised
      fluorescein-isothiocyanate (FITC)-labelled S. pneumoniae were allowed to attach
      to neutrophils, split into two aliquots and further incubated either at 4 degrees
      C (to avoid phagocytosis) or 37 degrees C (to allow phagocytosis). Cell-surface
      residual opsonic IgG was detected by phycoerythrin (PE)-conjugated anti-human IgG
      in both samples. The fraction of FITC-labelled bacteria phagocytosed via antibody
      (F(i)) could be estimated from FITC and PE labels, and reflected the opsonic
      activity of sera. The technique displayed high sensitivity for the detection of
      opsonic antibodies, as shown by experiments using pre- and post-immune sera,
      which documented significantly increased phagocytosis after vaccination, and the
      observed increase in phagocytosis rates at higher antibody levels. The intrinsic
      variation of the assay was low, and could be further reduced by the use of
      effector cells from donors with similar IgG receptor (FcgammaR) allotypes. The
      method described in this study should be generally applicable to test vaccine
      efficacy, to evaluate the interaction of bacteria and phagocytes, and to
      discriminate between antibody-mediated and antibody-independent interactions
      between bacteria and phagocytes.

PMID- 11334964
TI  - Flow cytometric evaluation of apoptosis, necrosis and recovery when culturing
      monocytes.
AB  - After developing and applying a method for cryopreserving monocytes, we found a
      substantial cell loss when culturing these cells. Monocytes were isolated from
      blood donors by density gradient centrifugation, purified by elutriation and
      cryopreserved. Thawed cells were cultured in ultra low attachment wells and
      studied with Annexin V, Propidium iodide, Dihexyloxacarbocyanine (DiOC(6)(3)),
      bromolated deoxyuridine triphosphate nucleotides (Br-dUTP), DNA ploidy and DNA
      ladder methodologies. The main cell loss was within the first 24 h and recovery
      on day 7 was 35-40%. The first 2-6 h of culture were found to be crucial for
      determining which cells survive. Initially (2-4 h), apoptosis was the main
      feature but after 6 h, necrosis dominated. Two populations of cells developed
      after 24 h: "A" consisting of larger cells with low levels of apoptosis and
      necrosis signals and population "B" comprising smaller cells with a high
      expression of necrotic but low levels of apoptotic signals. Signs of DNA
      fragmentation were slight. These early, dynamic changes may be important for the
      interpretation of experimental results when investigating monocytes in culture.

PMID- 11334965
TI  - An investigation into the suitability of silica beads for cell separations based
      on density perturbation.
AB  - This study has investigated possible alternative types of beads for fractionating
      cells on the basis of density perturbation. It is well known that uniform
      magnetic beads can be extremely important tools for separating cells by both
      magnetic separation techniques and density perturbation. However, because of the
      inherent expense associated with the use of magnetic beads, it was decided to
      study the possible use of inexpensive silica beads for density perturbation in
      terms of their attachment and modification of density of cells and to compare
      them with uniform Dynabeads. Silica beads were analyzed to determine their size
      and effect on the density of cells. Differentiated HL60 cells were used as a
      model system. As differentiation occurs, different levels of antigens are
      expressed on the cell surface and this results in different numbers of beads
      binding to cells. DMSO-differentiated HL60 cells were mixed with anti-CD11b
      coated beads at a ratio of 20:1 (beads/cell), and gentle mixing was carried out
      at 20 degrees C on the end-over-end mixer. The binding of antibody-coated silica
      beads and Dynabeads to partially differentiated HL60 cells were compared. The
      conclusions reached on the basis of these experiments are that antibody-coated
      silica beads (Ab-coated silica) can be used as alternative beads for some cell
      fractionations. However, compared with Dynabeads, there are more beads that are
      only transiently associated with cells, possibly indicating that higher levels of
      detachment of beads from cells occur when silica beads are used. In addition,
      silica beads are usually heterogeneous in size and this would make it difficult
      to use these beads for the isolation of purified subpopulations of differentiated
      cells.

PMID- 11334966
TI  - Cytolytic peptides induce biphasic permeability changes in mammalian cell
      membranes.
AB  - The cytolytic peptides melittin and gramicidin S are naturally occurring agents
      that provide a comparative model for studies of complement, immunotoxin and cell
      mediated membrane permeability. Most attempts to characterize cytolytic peptides
      have used model membrane systems including phospholipid vesicles or erythrocytes.
      Membrane vesicles permit the use of self-quenching concentrations of fluorescent
      permeability markers, while erythrocytes release measurable hemoglobin. Attempts
      at measuring early membrane permeability changes in nucleated mammalian cells
      have been limited. To measure the kinetics of mammalian cell membrane
      permeability changes induced by cytolytic peptides, we developed a 96-well
      fluorescence cytolysis assay using the cytoplasmic fluorescent dye calcein as the
      membrane permeability marker. To facilitate rapid assessment of membrane
      permeability, trypan blue was added to the assay solution to quench (a) released
      fluorescence and (b) retained intracellular fluorescence. Trypan blue also
      provided a complementary visual assessment of cell viability. Using this assay, a
      detailed kinetic analysis demonstrated permeability of the cell membranes within
      seconds of exposure to the cytolytic peptides. The rapid permeabilization of the
      cell membranes was confirmed by flow cytometry using the calcium indicator dye
      fluo-3. The assay also demonstrated a second slower phase of marker release over
      the next several hours. The fluorescence cytolysis assay was able to reliably
      detect the biphasic permeability changes associated with the melittin and
      gramicidin S peptides suggesting the potential utility of this assay in the
      assessment of other cytolytic agents.

PMID- 11334967
TI  - Monoclonal anti-acid-labile subunit oligopeptide antibodies and their use in a
      two-site immunoassay for ALS measurement in humans.
AB  - Quantification of the acid-labile subunit (ALS) has to date been restricted to
      immunoassays utilizing polyclonal antibodies. By immunization with N-terminal and
      C-terminal specific ALS oligopeptides, we generated monoclonal antibodies (mAbs)
      that target ALS-specific sequences outside the nonspecific leucine-rich repeats
      in the ALS molecule. For mAb selection, a special screening method was developed.
      Monoclonal antibody 5C9, which targets the N-terminus of ALS, is immobilized and
      the anti-ALS mAb 7H3, directed against the C-terminus, is biotinylated and used
      as tracer Ab. Due to the extreme pH-lability of ALS, changes in immunorecognition
      of ALS were investigated after acidification for protein unfolding in different
      pH ranges and in a time-dependent manner. It was determined that acidification of
      the serum samples to pH 2.7 for 30 min, followed by neutralization and dilution
      to 1:100 was the optimal acid-neutralization method. For standardization
      purposes, a serum pool derived from healthy volunteers was assigned the value 1
      U/ml ALS. The sandwich assay has a working range with a linear dose-response
      curve in a log/log system between 0.005 and 10 U/ml. ALS levels in seven
      acromegalic patients ranged from 2.0 to 4.2 U/ml, and in 12 untreated growth
      hormone deficient patients from 0.036 to 0.986 U/ml (mean=0.45 U/ml). After 12
      months of growth hormone therapy, ALS levels increased significantly to 1.18+/
      0.45 U/ml (mean+/-SD; p<0.0006). The increase ranged from 0.48 to 1.4 U/ml. The
      change in ALS with growth hormone (GH) therapy correlated closer with the change
      in IGF-I (r=0.798, p=0.0057; Spearman rank correlation) than with the change in
      insulin-like growth factor binding protein (IGFBP3; r=0.549, p=0.057). This
      specific sandwich assay for the measurement of ALS provides a potentially
      valuable indicator of growth hormone secretory status. With this mAb-based
      immunofluorometric assay, the nonspecific detection of other proteins containing
      leucine-rich repeat sequences can be excluded.

PMID- 11334968
TI  - Development of a novel flow cytometric cell-mediated cytotoxicity assay using the
      fluorophores PKH-26 and TO-PRO-3 iodide.
AB  - A flow cytometric (FCM) assay has been developed for the determination of cell
      mediated cytotoxicity (CMC). In the assay, the target tumour cell population was
      labelled with a membrane dye, PKH-26, prior to incubation with splenocyte
      effector cells. Cell death within the target population was assessed by the
      addition of the viability probe TO-PRO-3 iodide (TP3) and analysed by flow
      cytometry. The extent of cytotoxicity was determined by the relative number of
      live target cells labelled with PKH-26 only and dead, permeabilised cells
      labelled with both PKH-26 and TP3. This CMC method allows the analysis to be
      conducted on a single cell basis and overcomes the need for radiochemicals. This
      communication indicates that the FCM assay is an accurate and reproducible
      experimental system capable of analysing natural killer (NK) cell and antibody
      dependent cell-mediated cytotoxicity. The procedure is comparable to the chromium
      release assay. We believe that this is one of the first demonstrations of an FCM
      based antibody-dependent cell-mediated cytotoxicity (ADCC) assay.

PMID- 11334969
TI  - Generation of large numbers of human dendritic cells from whole blood passaged
      through leukocyte removal filters: an alternative to standard buffy coats.
AB  - Many blood banks now use whole blood inline filtration to produce leukocyte
      depleted blood products. As a result, a common source of large numbers of human
      dendritic cells (DC) for research purposes, namely standard buffy coats, has been
      lost. Therefore, we have adapted our conventional method for growing DC from
      CD14(+) precursors in order to make use of these filter units. A dextran solution
      containing human serum albumin was used to flush back the filters. After
      pelleting, mononuclear cells were obtained by standard density gradient
      centrifugation (Lymphoprep). To eliminate T cells, we used rosetting with sheep
      red blood cells. In addition to the classical PBMC, the cell population obtained
      after Lymphoprep centrifugation was found to contain high numbers of CD14(+)
      granulocytes which could be depleted by separation on an additional Percoll
      gradient. At this stage, FACS analysis revealed a cell population that resembled
      the CD14(+) monocyte-enriched population, obtained from traditional buffy coat
      preparations after Lymphoprep centrifugation and T cell elimination. Culture of
      the cells and the induction of maturation was identical to the previously
      described procedures, except that the culture time was reduced from 7 to 5 days
      and the maturation time from 3 to 2 days. Analyses of the major molecules
      indicative of DC maturation (CD83, CD86, CD208/DC-LAMP) and functional analyses
      of the T cell-stimulatory capacity of the DC population (using the MLR assay with
      normal peripheral T cells and naive T cells) revealed no major differences from
      buffy coat-derived DC preparations.

PMID- 11334970
TI  - Optimisation of an ELISA for the serodiagnosis of visceral leishmaniasis using in
      vitro derived promastigote antigens.
AB  - An antibody detection ELISA was developed for diagnosis of visceral
      leishmaniasis. Antigens released by Leishmania donovani promastigotes into a
      protein-free medium were used. SDS-PAGE analysis has indicated that Ld-ESM
      contain several protein antigens. Titration and chequer-board analyses were
      performed to optimise the assay protocol. Optimal results were obtained when
      antigen (50 microg/ml) was coated with PBS-methyl glyoxal buffer, and wells
      blocked with 0.5% casein. A serum dilution of 1:500 in antigen-coated wells,
      blocked with 0.5% casein, generated lowest absorbance with Ref-ve sera and higher
      absorbance with Ref+ve sera. All steps of the ELISA were performed at room
      temperature. The S/N ratio, the differential absorbance between the negative
      sample vs. the test or Ref+ve sample, was used to quantify the specific antigen
      and antibody reactions. An anti-human monoclonal antibody conjugated with HRP
      (MAb-conjugate) outperformed a commercially available anti-human polyclonal
      antibody conjugate (PAb-conjugate). The MAb-conjugate gave minimal background
      reactions with endemic sera. Optimised final assay steps mentioned below were
      used to evaluate sera samples from field trials. ELISA wells were coated with 50
      microg/ml Ld-ESM mixed in PBS-methyl glyoxal overnight, and after removing the
      antigen, blocked with 0.5% casein for 1 h at RT. Patient sera along with control
      sera, diluted to 1:500 in PBS/T, were reacted for 1 h at RT. After washing the
      plate with PBS/T, wells were reacted with MAb-conjugate for 40 min at RT, and
      after washing, binding of antibodies was visualized by using TMB as a chromogen
      substrate. The relative specific binding was quantified by the S/N ratio. A batch
      of n=22 endemic sera from North Africa were evaluated and resulted with 100%
      specificity and sensitivity, 99.99% PPV and 95.45% NPV. The specificity and
      sensitivity of this assay will be further evaluated in planned retrospective and
      prospective multi-site trials.

PMID- 11334971
TI  - Strategies to generate antibodies capable of distinguishing between proteins with
      >90% amino acid identity.
AB  - Protein engineering is a common strategy for the generation of protein variants
      with new properties. The engineered variants often have a high degree of
      similarity with the wild-type progenitor protein, necessitating a tool (e.g.,
      antibody) to distinguish the wild-type and variant protein forms. As part of an
      overall effort to understand the process of incorporation of amino acids into
      storage proteins during seed fill in soybean, we have engineered a variant of
      soybean vegetative storage protein beta (VSPbeta) that is 91.8% identical in
      amino acid sequence to the wild-type protein, but contains 10% methionine
      (VSPbeta-Met, unpublished results). Thus, it would be desirable to have
      antibodies that specifically recognize VSPbeta-Met over the endogenously
      expressed wild-type protein in transgenic plants. To this end, we compared three
      strategies for the isolation of VSPbeta-Met-specific antibodies: (1) hybridoma
      production using VSPbeta-Met protein as the antigen, (2) polyclonal antibody
      production in rabbits using a peptide antigen corresponding to a methionine-rich
      region of VSPbeta-Met, and (3) subtractive immunization in mice using VSPbeta-WT
      as the tolerogen, cyclophosphamide for immunosuppression and VSPbeta-Met as the
      immunogen. While the first strategy generated antibodies cross-reactive to both
      antigens, the second strategy generated polyclonal antibodies that preferentially
      recognized the variant protein in immunoblots. However, using subtractive
      immunization, we were able to generate mouse polyclonal antibodies that exhibited
      10-fold greater reactivity with VSPbeta-Met than VSPbeta-WT in an ELISA.

PMID- 11334972
TI  - Monitoring of cell viability and cell growth in a hollow-fiber bioreactor by use
      of the dye Alamar Blue.
AB  - We describe a method for monitoring cell proliferation in a small-scale hollow
      fiber bioreactor (culture volume: 1 ml) by use of the Alamar Blue dye. Alamar
      Blue is a non-fluorescent compound, which yields a fluorescent product after
      reduction, e.g. by living cells. In contrast to the MTT-assay, the Alamar Blue
      assay does not lead to cell death. However, when not removed from the cells, the
      Alamar Blue dye shows a reversible, time- and concentration-dependent growth
      inhibition as observed for the leukemic cell lines CCRF-CEM, HL-60 and REH. When
      applied in the medium compartment of a hollow-fiber bioreactor system, the dye is
      delivered to the cells across the hollow-fiber membrane, reduced by the cells and
      released from the cell into the medium compartment back again. Thus, fluorescence
      intensity can be measured in medium samples reflecting growth of the cells in the
      cell compartment. This procedure offers several advantages. First, exposure of
      the cells to the dye can be reduced compared to conventional culture in plates.
      Second, handling steps are minimized since no sample of the cells needs to be
      taken for readout. Moreover, for the exchange of medium, a centrifugation step
      can be avoided and the cells can be cultivated further. Third, the method allows
      discriminating between cell densities of 10(5), 10(6) and 10(7) of proliferating
      HL-60 cells cultivated in the cell compartment of the bioreactor. Measurement of
      fluorescence in the medium compartment is more sensitive compared to glucose or
      lactate measurement for cell counts below 10(6) cells/ml, in particular. We
      conclude that the Alamar Blue-assay combined with a hollow-fiber bioreactor
      offers distinct advantages for the non-invasive monitoring of cell viability and
      proliferation in a closed system.

PMID- 11334973
TI  - Assessment by flow cytometry of peripheral blood leukocyte enzymatic activities
      in HIV patients.
AB  - Leukocyte enzymatic activities are important in non-specific protection against
      bacterial infections, but traditional methods for the detection of intracellular
      enzymatic activities rely on cumbersome and complex assays. The development of
      specific substrates, which become fluorescent upon degradation of the biomolecule
      after its passive entry into intact cells, permits a simplified evaluation of
      leukocyte enzymatic activities. We have used this method to assess intracellular
      elastase, collagenase and cathepsin D activities of peripheral blood leukocytes
      using flow cytometry in a series of HIV patients and healthy controls. Monocytes
      displayed the highest enzymatic activities for the three proteases tested. In HIV
      infected patients, the collagenase and cathepsin D activities of monocytes were
      significantly lower, whereas the elastase and cathepsin D activities of
      polymorphonuclear cells were elevated. Slightly higher elastase activity was
      detected in the lymphocytes of patients. This study demonstrates the feasibility
      of this new method for the study of intracytoplasmic enzymatic activities.
      Significant variations were observed in the peripheral blood of HIV-infected
      patients and different patterns were especially evident in monocytes and
      polymorphonuclear cells.

PMID- 11334974
TI  - A new multiplex PCR strategy for the simultaneous determination of four genetic
      polymorphisms affecting HIV-1 disease progression.
AB  - The CCR5 Delta32, CCR2 64I, SDF1 3'A, and CCR5 promoter 59029 polymorphisms have
      been suggested to influence HIV-1 disease progression. Furthermore, the CCR5
      Delta32 and the CCR2 64I polymorphisms have been associated with various other
      diseases. The purpose of the present study was to develop a multiplex assay for
      the simultaneous determination of these four polymorphisms. Results obtained with
      the multiplex assay were compared to results obtained by conventional RFLP-PCR
      and no differences were observed. The multiplex assay offers a quick tool for the
      determination of the CCR5 Delta32, CCR2 64I, SDF1 3'A, and CCR5 promoter 59029
      A/G polymorphisms.

PMID- 11334975
TI  - Development of an enzyme-linked immunoassay for the quantification of YKL-40
      (cartilage gp-39) in guinea pig serum using hen egg yolk antibodies.
AB  - An indirect competition immunoassay for the quantification of YKL-40 (cartilage
      gp-39, Chondrex) in guinea pig serum has been developed using egg yolk antibodies
      (IgY). The immune response of hens to YKL-40 was verified by immunoblot analyses.
      Highly specific antibodies were obtained 30 days after the first injection. The
      ELISA was developed in 96-well microtiter plates with quadruplicate
      determinations for each point. The assay was based on the ability of YKL-40
      present in serum to displace the binding of antibodies to the coated antigen. An
      inhibition mixture containing standard YKL-40 or guinea pig serum, diluted 1/5,
      and primary antibodies, diluted 1/5000, was allowed to equilibrate for 2 h at
      room temperature and dispensed for 16 h at 4 degrees C in wells coated with 1
      microg/ml of YKL-40. Detection was achieved by the addition of rabbit anti
      chicken antibodies conjugated to peroxidase followed by tetramethylbenzidine.
      Specificity was assessed by parallelism between a dilution curve of serum and
      standard YKL-40. The sensitivity of detection was 10 ng/ml. Intra- and interassay
      coefficients of variation were both 8.7%. The analytical recovery was 101.5+/
      5.4% (mean+/-standard deviation (SD), n=9). The YKL-40 concentration in serum
      from 12 adult guinea pigs was 330+/-216 ng/ml (mean+/-SD) with a lower value of
      164 ng/ml and an upper value of 982 ng/ml. In contrast to the rat, a dilution
      curve of rabbit serum gave parallelism with the guinea pig standard, suggesting
      recognition of a similar epitope. Possible applications of the assay in the
      guinea pig include disease models where YKL-40 is overexpressed and could be used
      as a marker, i.e. osteoarthritis, rheumatoid arthritis, cancer, liver fibrosis,
      atherosclerosis and more generally, pathologies with increased tissue remodeling.

PMID- 11334976
TI  - Influence of a transiently transfected gene on apoptosis, measurements guided by
      cotransfected GFP.
AB  - A rapid and quantitative flow cytometric method simultaneously identifying cells
      that incorporated a gene of interest in a transient electroporation and
      discriminating between dead, live and apoptotic states in a single measurement is
      presented. An expression vector encoding the gene of interest was cotransfected
      with a plasmid carrying the green fluorescent protein (GFP). Subsequently, the
      cultured cells were stained with 7-amino-actinomycin D (7-AAD) without fixation
      and were subjected to a multivariate analysis. The value of the method and its
      high reproducibility were demonstrated on Jurkat cells. Those cells were
      transiently transfected with a construct expressing a short C-terminal fragment
      of presenilin 1 (PS1-f) known to show anti-apoptotic properties. The PS1-f gene
      was under the control of the tetracycline-responsive transactivator.

PMID- 11334977
TI  - Biotinylation of protein complexes may lead to aggregation as well as to loss of
      subunits as revealed by Blue Native PAGE.
AB  - Blue Native polyacrylamide gel electrophoresis (BN-PAGE) is a high-resolution
      method for studying native protein complexes. Here, the migration behaviour of
      the B cell antigen receptor (BCR) in BN-PAGE with and without prior biotinylation
      of the cell surface, from which the complexes were purified, are compared. Non
      biotinylated complexes appear as a single band, whereas biotinylated complexes
      display several bands, indicating that biotinylation leads to aggregation of
      complexes as well as to loss of subunits. Thus, BN-PAGE has limitations in
      studying multiprotein complexes. These results are used to gain insight into the
      stoichiometry of the complex.

PMID- 11334978
TI  - Profiling of gene expression in individual hematopoietic cells by global mRNA
      amplification and slot blot analysis.
AB  - The pattern of expressed genes defines the structure and functional status of
      cells. Currently, most methods used in gene expression studies depend on large
      numbers of cells. Thus, their application may be hampered by the heterogeneity of
      cell populations, and by the low numbers of cells obtainable from in vivo
      sources. Such drawbacks may be overcome by methods suitable for the profiling of
      gene expression at the single cell level. We studied whether polymerase chain
      reaction (PCR) products synthesized from individual cells by global amplification
      of messenger RNA (mRNA) were suitable as probes for gene expression analysis. For
      this purpose, cells were subjected to reverse transcription and PCR using
      sequence independent primers (SIP RT-PCR). The resultant cDNA products were
      radiolabeled and hybridized to cDNA clones arrayed on a nylon membrane by vacuum
      slot blotting (a method referred to as slot blot analysis). The SIP RT-PCR
      procedure was reproducible and allowed the detection of twofold changes in input
      RNA copies per cell (range: 80-10.000 copies of an in vitro transcribed poly(A)
      tailed RNA/cell). Analysis of total RNA and amplified cDNA, obtained from
      neutrophil granulocytes and the promyelocytic HL-60 cell line, demonstrated
      comparable gene expression profiles as measured by Northern blot and slot blot
      analysis. Slot blot analysis of HL-60 cells indicated that individual cells from
      an apparently homogenous population have varying expression of specific
      transcripts, which all contribute to the mRNA phenotype of their population.
      Interestingly, the genes that were detected in some but not all individual HL-60
      cells were those found to peak within 2 days of retinoic acid-induced
      granulocytic differentiation. This study demonstrates the potential of cDNA,
      synthesized from individual cells by global amplification of mRNA, as probes for
      cDNA arrays.

PMID- 11334979
TI  - Specific oligobodies against ERK-2 that recognize both the native and the
      denatured state of the protein.
AB  - Oligonucleotide aptamer(s), obtained by using the SELEX procedure, has been used
      as reagents to recognize different molecules with high affinity and specificity.
      However, until recently, it was not possible to obtain oligonucleotide-based
      reagents able to recognize proteins with high specificity in assays typical of
      antibodies, such as immunohistochemistry, Western blotting and
      immunoprecipitations. Here, we show the results obtained by applying the strategy
      of "target switching" to obtain specific polyclonal and monoclonal oligobodies
      against the protein ERK2. We were able to develop highly specific polyclonal
      oligobodies by using only one selection step with a temporary target and one
      selection step with the final target (ERK2). Since only two selection steps were
      required, these results demonstrate that it is possible to obtain specific
      reagents against a protein without a need for an "in vitro evolution" using many
      selection steps, or error-prone polymerases. After one additional selection step,
      the polyclonal oligobodies were cloned to obtain a highly specific monoclonal
      oligobody.

PMID- 11334980
TI  - High level expression of a human rabies virus-neutralizing monoclonal antibody by
      a rhabdovirus-based vector.
AB  - Humans exposed to rabies virus must be promptly treated by passive immunization
      with anti-rabies antibody and active immunization with rabies vaccine. Currently,
      antibody prepared from pooled human serum or from immunized horses is utilized.
      However, neither of these reagents are readily available, entirely safe, or
      consistent in their biological activity. An ideal reagent would consist of a
      panel of human monoclonal antibodies. Such antibodies are now available, their
      only drawback being the cost of production. Using recombinant technology, we
      constructed a rabies virus-based vector which expresses high levels
      (approximately 60 pg/cell) of rabies virus-neutralizing human monoclonal
      antibody. The vector is a modified vaccine strain of rabies virus in which the
      rabies virus glycoprotein has been replaced with a chimeric vesicular stomatitis
      virus glycoprotein, and both heavy and light chain genes encoding a human
      monoclonal antibody have been inserted. This recombinant virus can infect a
      variety of mammalian cell lines and is non-cytolytic, allowing the use of cell
      culture technology routinely employed to produce rabies vaccines.

PMID- 11334981
TI  - ELISPOT assay to measure antigen-specific murine CD8(+) T cell responses.
AB  - The enzyme-linked immunospot technique (ELISPOT) relies on the visualization of
      cytokine secretion by individual T cells following in vitro stimulation with
      antigen. This assay has been developed and standardized for the quantitative
      detection of antigen-specific CD8(+) T cells in mice subjected to different
      immunization protocols [J. Immunol. Methods 181 (1995) 45]. We have identified
      important variables that affect the efficacy of the ELISPOT assay and in this
      protocol we describe this methodology in detail. As a model, we used the
      production of interferon-gamma by CD8(+) T cells from peripheral blood, spleen
      and liver of mice immunized with malaria sporozoites expressing the H-2K(d)
      restricted SYVPSAEQI. This protocol has also been used successfully to detect Th1
      and Th2 epitope specific CD4(+) T cells.

PMID- 11334983
TI  - Introduction to the supplement.

PMID- 11334984
TI  - The role of non-conventional MR techniques to study multiple sclerosis patients.
AB  - Conventional magnetic resonance imaging (MRI) lacks pathological specificity to
      the heterogeneous substrates of multiple sclerosis (MS) lesions and is not able
      to detect subtle, disease-related changes in the normal-appearing white matter
      (NAWM). As a consequence, the correlation between MRI findings and the long-term
      evolution of MS is moderate at best. To overcome the limitations of conventional
      MRI, new quantitative magnetic resonance (MR) techniques, such as cell-specific
      imaging, magnetization transfer imaging (MTI), proton magnetic resonance
      spectroscopy (MRS), diffusion-weighted imaging (DWI) and functional MR imaging
      (fMRI) have all been recently applied to the study of MS. These techniques should
      provide more accurate and pathologically specific estimates of the MS lesion
      burden than conventional MR and should improve our understanding of the
      mechanisms leading to MS-related irreversible disability.

PMID- 11334985
TI  - The physical basis of diffusion-weighted MRI.
AB  - Diffusion-weighted (DW) magnetic resonance imaging (MRI) is the only technique
      that permits a non-invasive in vivo assessment of water molecular diffusion,
      which reflects tissue configuration at a microscopic level. Therefore, this
      technique appears to be particularly useful in monitoring brain abnormalities.
      However, the quantitative measurement of diffusion is not without problems, which
      may limit the widespread use of diffusion-weighted MRI. In this report, the
      phenomenon of diffusion is described, together with its effect on the nuclear
      magnetic resonance signal. The concepts of diffusion anisotropy and diffusion
      tensor are also introduced, and the technical and hardware requirements are
      discussed.

PMID- 11334986
TI  - Acute and chronic changes of the apparent diffusion coefficient in neurological
      disorders--biophysical mechanisms and possible underlying histopathology.
AB  - Diffusion-weighted imaging (DWI) of the brain has become a valuable tool for the
      reliable detection and diagnosis of several neurological disorders. Although DWI
      is in wide use in daily practice, the underlying biophysical mechanisms that
      contribute to changes in the apparent diffusion coefficient (ADC) are still under
      discussion. Alterations in the apparent water diffusion rate reflect pathological
      changes in the brain tissue state, via changes in the diffusion characteristics
      of the intra- and extra-cellular water compartments including restricted
      diffusion, water exchange across permeable boundaries, the concept of the extra
      cellular tortuosity and the intra- and extra-cellular volume fraction. A
      reduction of the ADC has been detected in acute neurological diseases, while
      disease states associated with dominant acute vasogenic edema formation or
      chronic tissue destruction usually show elevations of the ADC. Compromise of
      energy metabolism is likely to contribute to a reduction of the ADC while already
      minor structural disintegration may contribute to elevations of the ADC.

PMID- 11334987
TI  - Applications of DWI in clinical neurology.
AB  - Echo planar diffusion-weighted imaging (EP DWI) provides information about the
      physiologic state of the brain that is not available on conventional magnetic
      resonance (MR) images. Specifically, it provides signal proportional to the
      molecular diffusion of water molecules. It has proven highly sensitive in the
      detection of acute infarction and it is reliable in differentiating acute stroke
      from other diseases that mimic acute stroke clinically and on conventional MR
      images. With perfusion imaging, diffusion-weighted imaging is useful in
      predicting final infarct size and patient outcome. Diffusion MR is also becoming
      increasingly useful in the evaluation of a wide variety of other disease
      processes including neoplasms, intracranial infections and traumatic brain
      injury. Because acute stroke is common in the differential diagnosis of the
      majority of patients who present with acute neurologic deficits, diffusion
      weighted imaging has become an essential sequence.

PMID- 11334988
TI  - Overview of diffusion-weighted magnetic resonance studies in multiple sclerosis.
AB  - Diffusion-weighted magnetic resonance imaging (DW-MRI) provides a unique form of
      MR contrast that enables the diffusional motion of water molecules to be
      quantitatively measured. As a consequence, DW-MRI provides information about the
      size, shape, integrity, and orientation of brain structures. Pathological
      processes able to alter tissue integrity by removing or modifying some of the
      structural barriers that normally restrict water molecular motion in biological
      tissues cause changes in water diffusion characteristics, which can be measured
      in-vivo using DW-MRI. Although DW-MRI has been shown to be of great clinical
      utility in the assessment of patients with cerebral ischemia, it is also
      increasingly being used to quantify in-vivo the extent and severity of multiple
      sclerosis (MS) pathology. The pathological elements of MS have the potential to
      alter the permeability or geometry of structural barriers to water molecular
      motion in the brain, optic nerve and spinal cord. The present review outlines the
      major contributions given by DW-MRI for the quantification of MS-related damage
      and for the understanding of MS pathophysiology.

PMID- 11334989
TI  - Diffusion-weighted imaging of the spinal cord and optic nerve.
AB  - The optic nerve and spinal cord are technically challenging to investigate with
      any magnetic resonance imaging (MRI) technique due to the effect of the
      surrounding cerebrospinal fluid and lipid, and the presence of nearby bony
      structures. Motion and the relatively small cross-section of the structures make
      diffusion-weighted imaging even harder. With careful choice of pulse sequence and
      parameters, however, apparent diffusion coefficient (ADC) measurements are now
      possible in the optic nerve, and both ADC and diffusion tensor imaging (DTI)
      measurements are becoming available in the spinal cord.

PMID- 11334990
TI  - Using diffusion-weighted MRI in multicenter clinical trials for multiple
      sclerosis.
AB  - This paper reviews the current state of knowledge about the use of diffusion
      weighted MRI in the field of multiple sclerosis (MS) research. The contribution
      that diffusion-weighted imaging has made to our understanding of MS is critically
      appraised, and pointers are given to the sort of work that needs to be done
      before diffusion-weighted MRI could be recommended for inclusion in a clinical
      trial. The types of procedures that would be needed for quality assurance of
      diffusion data, and the data collection schemes that would lead to reliable data,
      are then reviewed. The quantitative nature of diffusion MRI makes it an
      attractive proposition for inclusion in clinical trials for MS therapeutic
      agents, but without further validation work with clinical correlates cannot be
      recommended at present.

PMID- 11334991
TI  - Future applications of DWI in MS.
AB  - Diffusion imaging is a noninvasive technique for measuring the movement of water
      molecules. Although it has had its greatest impact thus far in the area of stroke
      imaging, the information garnered from diffusion experiments can provide an
      indication of myelin injury and perhaps axonal integrity. In this paper, we
      describe some current and potential future applications of diffusion imaging in
      multiple sclerosis. These include the use of global indices such as diffusion
      trace and anisotropy, as well as implementation of axonal fiber tracking
      methodologies for assessment of axonal integrity and connectivity between
      cortical regions.

PMID- 11334992
TI  - Dendritic cell vaccination protects mice against lethality caused by genital
      herpes simplex virus type 2 infection.
AB  - We have evaluated the ability of antigen pulsed bone-marrow derived dendritic
      cells (bmDC), to induce protective immunity against a genital tract infection
      with herpes simplex virus type 2 (HSV-2) in mice. Intravenous but not vaginal
      administrations of bmDC pulsed in vitro with UV-inactivated HSV-2, or with
      purified HSV-2 envelope glycoproteins gave rise to complete protection against
      disease, as well as death caused by genital herpes infection. Protection was
      dependent on the antigens being presented by the bmDC as neither the antigens
      alone, nor the mock-pulsed bmDC prevented disease. Immunity was associated with
      HSV-2 specific IFN-gamma and antibody production, and was shown to be dependent
      on CD4(+) cells secreting IFN-gamma. Thus, ex vivo antigen-pulsed bmDC represents
      a powerful tool for the study of protective immunity to genital herpes infection,
      and for the identification of protective antigens. These findings might also have
      an impact on the design of vaccines against other sexually transmitted viral
      diseases.

PMID- 11334993
TI  - Murine ectoplacental cone-derived trophoblast cells express chemokine receptors.
AB  - Chemokine receptors (CCRs) have been shown to regulate T cell migration and
      differentiation as well as the establishment of Th1/Th2 bias. Furthermore, T
      cells and T cell products are essential to trophoblast development. Thus,
      postulating that chemokines as well as their receptors may be expressed by
      trophoblast to move T cells into an interaction with the feto-placental unit, we
      examined whether CCRs are expressed during the early stages of ectoplacental cone
      (EPC) formation. For this, murine EPC-derived trophoblast were examined for their
      ability to express CCRs constitutively or inducible by interferon-gamma (IFN
      gamma). Immunofluorescence experiments on EPC-derived trophoblast cells showed
      that CCR3, CXCR4 and CCR5 are significantly expressed. IFN-gamma accelerated the
      mobilization of intracellular pools of CCR molecules during early cell culture
      periods (2-6 h) and, in most cases, increased their expression on EPC-derived
      trophoblast cells. CCR activity could be detected in the culture supernatants of
      these cells, inversely proportional to cell surface expression, suggesting the
      existence of rapid endocytosis and recycling mechanisms. This finding indicates
      that the level of intracellular CCRs may partly be determined in the
      extracellular matrix, an event that could play an important role towards
      neutralization of specific T cell/trophoblast interactions during early stages of
      pregnancy and protect the fetus against harmful maternal immune responses.

PMID- 11334994
TI  - Neonatal ingestion of IgG-containing milk increases the survival of adoptively
      transferred B-lineage cells in B cell-deficient mice.
AB  - This study shows that neonatal ingestion of immunoglobulin-containing milk
      increases the survival of adoptively transferred B-lineage cells in non
      irradiated B cell-deficient (mu-/-) mice. Neonatal mu-/- mice were either
      transferred to lactating mu+/+ foster dams, allowing them to suckle IgG
      containing milk, or were kept with their mu-) dams, without IgG in the milk.
      After adoptive transfer of spleen cells as adults, serum-IgG levels, numbers of
      plasma cells, T and B cells in spleen and bone marrow were determined. The
      results showed that the mice which had received milk-IgG had significantly higher
      levels of serum-IgG and splenic B cells, as well as a higher number of Ig
      secreting cells in spleen and bone marrow. This indicates that the mice might
      have been tolerised against IgG as neonates, if allowed to ingest Ig-containing
      milk. There is, however, a possibility that B cells in the milk may also
      contribute to the observed tolerising effect. In summary, the results suggest
      that 'cross-fostering' could be a suitable method to facilitate the long-term
      reconstitution of B- and plasma cell numbers in non-irradiated B cell-deficient
      mice.

PMID- 11334995
TI  - Identification of rat prostatic steroid binding protein (PSBP) as an
      immunosuppressive factor.
AB  - Prostatic steroid binding protein (PSBP) is the major protein produced (
      approximately 20% of the total cytosolic protein) and secreted into the seminal
      fluid by the rat ventral prostate but its physiological function has not been
      elucidated yet. Since PSBP is secreted into the seminal fluid (which is itself a
      potent immunosuppressor) and has strong homology with uteroglobin (which possess
      an important anti-inflammatory function) our aim was to determine what effect, if
      any, PSBP would have on the immune system. With that purpose in mind we performed
      mononuclear cell cultures in the presence or absence of purified PSBP and
      analysed the effect of this protein on different functional parameters. PSBP
      inhibits the mitogen-induced proliferation of normal rat spleen mononuclear cells
      (MNC) specifically and in a dose-dependent manner. It reduces the production of
      IL-2 and the expression of its receptor (analysed by flow cytometry) which are
      important events for lymphocyte proliferation. Also, PSBP was able to inhibit OVA
      specific proliferation of lymph node cells from previously primed animals. The
      immunosuppressive effect of PSBP is not due to an inherent toxic effect to the
      cells, since the cell viability was kept intact at the different times of culture
      studied. We also analysed the effect of rat PSBP on mitogen-induced proliferation
      of mouse spleen and human blood MNC. The proliferation was strongly abolished in
      a dose-dependent and non-species specific fashion. Moreover, PSBP strongly
      inhibits the human mixed lymphocyte reaction. Taken together, the present data
      support evidence for a new type of function for PSBP. We report that PSBP is a
      potent immunosuppressor factor and we describe its effect on the immune function
      in vitro. Here, we discuss the possible implications of these findings in the
      protection of sperm from immunologic damage in the feminine reproductive tract.

PMID- 11334996
TI  - Influence of menstrual cycle on NK activity.
AB  - Natural killer (NK) cells are CD3- CD56+ and/or CD16+ cytotoxic lymphocytes that
      mediate first-line defense against various types of target cells without prior
      immunization. To assess the effect of the menstrual cycle and gender on NK
      activity we evaluated 30 healthy women (mean age 28.1 years, range 21-39) in
      follicular and luteal phases, 29 postmenopausal women (mean age 58.8 years, range
      42-72) and 48 healthy men (mean age 31.6 years, range 21-40). In a flow
      cytometric test of NK activity, peripheral blood mononuclear effector cells were
      mixed with K562 targets cells labeled with DiO (3,3'-dioctadecyloxacarbocyanine
      perchlorate) at effector:target cell ratios of 40, 20, 10 and 5:1. Dead cells
      were stained with propidium iodide and results were expressed as lytic units per
      10(7) cells. In addition, progesterone levels were determined in the luteal phase
      of the menstrual cycle of healthy women by a chemiluminescence assay. Our results
      showed that (1) NK cytotoxicity was higher in the follicular than in the luteal
      phase of the menstrual cycle (P < 0.0001); (2) postmenopausal women and men
      showed NK activity similar to women in the follicular phase but higher than women
      in the luteal phase of the menstrual cycle (P < 0.05); and (3) there was no
      correlation between NK activity and levels of progesterone. The data suggest that
      progesterone does not influence NK activity directly and that other factors may
      explain the reduction of NK activity in the luteal phase of the menstrual cycle.

PMID- 11334997
TI  - Increased extracellular magnesium modulates proliferation in fetal neural cells
      in culture.
AB  - Retrospective studies have shown that antenatal magnesium may decrease the risk
      of cerebral injury in preterm infants, leading to several ongoing trials of
      tocolytic magnesium as a neuroprotective agent. However, other studies have
      indicated that antenatal magnesium actually increases neonatal mortality, leaving
      it unclear if magnesium is protective or dangerous to preterm infants. This
      controversy may be secondary to our limited understanding about the mechanisms of
      magnesium's action on the fetal brain. We therefore investigated the effect of
      increasing extracellular magnesium on cultures of neurons from embryonic day 6
      telencephalon. Conversion of MTT (3-(4,5-dimethyl, thiazol-2-yl)-2,5
      diphenyltetrazolium bromide) by intact mitochondria was taken as a measure of
      cell viability. Nuclear incorporation of BrdU (5-bromo-2'-deoxyuridine) was taken
      as a measure of cell proliferation. Exposure of cultures for 24 h to a 4-fold
      increase in magnesium (3.3 mM) increased both overall cell viability (P<0.002)
      and proliferation (P<0.02) by approximately 50%. Proliferating cells showed
      characteristics of glial cell precursors but magnesium had no effect on mature
      astrocyte proliferation. Increased Akt activation was observed following
      magnesium treatment, comparable to that observed with the growth factor insulin,
      suggesting one mechanism for proliferation. However, when apoptosis was induced
      in these cultures with the phosphatidylinositol-3-kinase inhibitor wortmannin,
      magnesium significantly enhanced cell death. Thus under normal conditions in the
      fetus, magnesium may be a positive factor but during stress it may exacerbate
      cell injury. This is the first time increased extracellular magnesium has been
      shown to increase cell proliferation in neural cells in culture or suggested to
      induce Akt activation.

PMID- 11334998
TI  - Parallel induction of the formation of dopamine and its metabolites with
      induction of tyrosine hydroxylase expression in foetal rat and human cerebral
      cortical cells by brain-derived neurotrophic factor and glial-cell derived
      neurotrophic factor.
AB  - Brain-derived neurotrophic factor (BDNF; 50 ng/ml), dopamine (DA; 10 microM) and
      forskolin (Fsk; 10 microM) have previously been shown by this and other
      laboratories to induce the tyrosine hydroxylase (TH) enzyme in foetal human and
      rat cerebral cortex during specified sensitive developmental periods. In the
      present study, these findings were extended for human and rat cells by showing
      that the induced TH+ cells also produce dopamine and its metabolite 3,4
      dihydroxyphenylacetic acid (DOPAC). In addition to this, TH induction and DA plus
      DOPAC production was observed in foetal human and rat cerebral cortex by using
      glial-cell derived neurotrophic factor (GDNF) in place of BDNF. The degree of
      induction by GDNF (1-10 ng/ml) was similar to that produced by BDNF and did not
      increase further when the two neurotrophic factors were used together. The time
      course of induction in human cultures was followed: GDNF was found to cause a
      more rapid induction process than BDNF during the first 2 weeks. However the
      degree of induction after 3 weeks was the same for both neurotrophic factors.
      Inhibitors of transcription (actinomycin D) or of translation (cycloheximide)
      eliminated all the increase in DA+DOPAC contents elicited by these compounds,
      indicating that de novo transcription and translation were required for increased
      expression of the TH and other related enzymes. The intracellular pathways by
      which these molecules exert this dopaminergic phenotype induction effect are
      discussed. This study indicates a new source of dopaminergic brain tissue for use
      as transplants to neurosurgically treat Parkinson's disease patients.

PMID- 11335000
TI  - Sources and sink of retinoic acid in the embryonic chick retina: distribution of
      aldehyde dehydrogenase activities, CRABP-I, and sites of retinoic acid
      inactivation.
AB  - Previous experiments in mice and zebrafish led to the hypothesis that an
      asymmetric distribution of the transcriptional activator retinoic acid (RA)
      causes ventral-dorsal polarity in the vertebrate eye anlage. A high concentration
      of RA in the ventral retinal neuroepithelium has been suggested to induce
      developmental events that finally establish topographic order in the retinotectal
      projection along the vertical eye axis. In the present study we have investigated
      potential sources and sinks of RA during embryonic development of the chick
      retina. At embryonic day (E)1 to E2, when the spatial determination of the eye
      primordia takes place, no RA synthesis by aldehyde dehydrogenases was detectable,
      and neither immunoreactivity for retinaldehyde dehydrogenase RALDH-2 nor for
      cellular retinoic acid binding protein CRABP-I was observed. These components of
      RA signal transduction appeared in the eye between E3 and E5. At later stages, RA
      measurements with a reporter cell line showed highest synthesis in the retinal
      pigment epithelium (RPE) and at the ventral and dorsal poles of the retina. RA
      degradation occurred mostly in a horizontal region in the middle of the retina
      with only small differences along the nasal-temporal axis. CRABP-I
      immunoreactivity appeared first in differentiating retinal ganglion cells with no
      indication of a spatial gradient across the ventral-dorsal eye axis. RA
      production depended on three NAD+-dependent enzyme activities, which could be
      competitively inhibited by citral. One enzyme, located in the dorsal retina
      (corresponding to mouse RALDH-1), and one enzyme in the RPE (RALDH-2) were
      aldehyde dehydrogenases of the same molecular weight (monomers about 55 kDa) but
      with different isoelectric points (6.5-6.9; 4.9-5.4). The third RA-synthesizing
      activity (pI 6.0-6.3) was limited to the ventral retina, and likely corresponded
      to mouse RALDH-3. The restricted localization of retinoid-metabolizing activities
      along the dorsal-ventral axis of the embryonic chick retina does support the idea
      that RA is involved in dorsal-ventral eye patterning. However, the late time of
      appearance of aldehyde dehydrogenase activities and CRABP-I points to functions
      in cellular differentiation that are distinct from the initiation of the dorsal
      ventral polarity.

PMID- 11334999
TI  - Ontogeny of ionotropic glutamate receptor expression in human fetal brain.
AB  - Glutamate receptors have multiple roles in the central nervous system. Recent
      evidence suggests that the iontropic glutamate receptors are critical during
      brain development, particularly for corticogenesis, neuronal migration, and
      synaptogenesis. In this study, we examined subunit mRNA expression and binding
      sites of the NMDA, AMPA, and kainate receptors from gestational weeks 8-20 in
      human fetal brain. Expression of glutamate receptors was high during several
      periods in these brains. Different levels of expression of each NMDA, AMPA, and
      kainate receptor subunit transcripts were present during development, with a
      greater abundance of NR1, NR2B, NR2D, GluR7, and KA1 mRNA at most gestational
      ages. Binding sites for NMDA, AMPA, and kainate receptors were all detected, but
      each had a unique pattern of expression. These results demonstrate that glutamate
      receptors are expressed early in human brain development, and undergo complex
      changes over time consistent with their role in normal development.

PMID- 11335001
TI  - Developmental impairment of auditory evoked N1/P2 component in rats
      undernourished in utero: its relation to brain serotonin activity.
AB  - In utero undernourishment produces an elevation of L-tryptophan and serotonin in
      the brain, including the auditory cortex (A1), such changes seem to be related to
      an increase in the free fraction (FFT) of plasma L-tryptophan that is transported
      into the brain through the blood-brain barrier, where it is taken up by
      serotonergic neurons for serotonin synthesis. Our observations support that FFT
      has a positive correlation with L-tryptophan (L-Trp) and serotonin levels in the
      auditory cortex (r=0.95 and 0.82, respectively). Interestingly, a decreased
      intensity dependence of the auditory evoked N1/P2 component was found in
      gestationally undernourished animals during their postnatal development. The
      N1/P2 component had a negative correlation (r=0.81) with A1 serotonin, such that
      it reflects changes in the neurotransmitter concentration. The present
      observations suggest a relevant role of serotonin in modulating the activity of
      the auditory cortex. Since the N1/P2 component is mainly associated with the
      activity of A1 neurons, it may well be that perception of auditory information is
      impaired during this developmental period, in the early undernourished animals,
      possibly affecting cognitive processes. This may be relevant to humans since low
      birth weight babies that also suffered gestational undernourishment (fetal
      placental insufficiency) present an increase in plasma FFT from birth up to 3
      months of age. These findings support that the plasma FFT and the intensity
      dependence of the auditory evoked N1/P2 component relate one another and may be
      markers of changes of the brain serotonergic activity.

PMID- 11335002
TI  - Morphology of CA3 non-pyramidal cells in the developing rat hippocampus.
AB  - Although several investigations have shown that the local GABAergic circuit in
      the rat hippocampus is functional very early in development, this result has not
      been yet completed by the investigation of the full dendritic and axonal
      arborization of the neonatal interneurones. In the present study, intracellular
      injection of biocytin was used to assess the branching pattern of interneurones
      in the hippocampal CA3 region of rat between 2 and 6 days of age. Based on their
      dendritic morphology, the biocytin-filled interneurones were divided into four
      classes: bipolar, stellate, pyramidal-like and fusiform interneurones. About half
      of the biocytin-filled neonatal interneurones exhibited dendritic or somatic
      filopodial processes. The axonal arbors of the filled-interneurones were widely
      spread into the CA3 region, and in four out of nine cases extended beyond the CA3
      region to branch into the CA1 region. These results show that, despite immature
      features, the filopodial processes, the hippocampal interneurones are well
      developed early in development at a time when their target cells, the pyramidal
      neurones, are still developing. These observations are consistent with a trophic
      role that GABA may play early in development.

PMID- 11335003
TI  - A comparative study of Purkinje cells in two RORalpha gene mutant mice: staggerer
      and RORalpha(-/-).
AB  - The staggerer (Rora(sg/sg)) mutation is a deletion in the RORalpha gene, one
      member of a family of nuclear receptor genes related to the retinoic acid
      receptor. Recently Steinmayr et al. (Proc. Natl. Acad. Sci. USA 95 (1998) 3960)
      generated a RORalpha null-mutant mouse (Rora(-/-)) by using a targeting vector in
      which a beta-Gal gene replaces the second finger of the DNA-binding domain of
      RORalpha. The Rora(-/-) cerebellum is qualitatively a phenocopy of the
      Rora(sg/sg) one, but the two strains differ slightly in their motor skills. To
      address the question whether the morphological defects in the Rora(-/-)
      cerebellum are identical to the Rora(sg/sg) one, we compared number and size of
      Purkinje cells in both staggerer and RORalpha null-mutant mice, using calbindin
      (CaBP) immunohistochemistry and revelation of beta-Gal activity. Compared to
      control cerebella the Rora(sg/sg) cerebellum has 82% fewer CaBP-positive cells.
      In Rora(-/-) mouse, all the the beta-Gal-positive Purkinje cells also expressed
      CaBP, but the cerebellum contained 78% less CaBP-positive cells than control, a
      deficit not different from the one observed in Rora(sg/sg). We show similar
      mediolateral compartments in Purkinje cell number and cytological abnormality in
      Rora(sg/sg) and Rora(-/-) mice. These results provide quantitative support for
      the hypothesis that the cerebellar phenotype in the homozygous Rora(sg/sg) is due
      to the lack of function of the RORalpha gene.

PMID- 11335004
TI  - Developmental patterns of NF-kappaB activation during acute hypoxia in the caudal
      brainstem of the rat.
AB  - NF-kappaB, an ubiquitous transcription factor which plays a major role in the
      regulation of stress-related genes, is activated during environmental hypoxia in
      the dorsocaudal brainstem of adult rats. To examine the developmental pattern of
      NF-kappaB basal activity in the brainstem and the response to hypoxia,
      electromobility shift assays and immunohistochemical staining for the P65 subunit
      of NF-kappaB were performed in caudal brainstem samples of rats at 2, 5, 10, 15,
      and 60 days postnatal age, following normoxic or hypoxic (1 h in 10% O2)
      exposures. In addition, the expression of IkappaB-alpha, and IkappaB kinases
      (ikk)-alpha and -beta was also examined using Western blots. Basal NF-kappaB
      nuclear activity and nuclear P65 immunoreactivity increased with maturation. In
      contrast, hypoxia induced enhanced activation of NF-kappaB and nuclear
      translocation of P65 in youngest animals. Expression of both IkappaB-alpha and
      ikk-alpha was highest in the more immature rats, and decreased with postnatal
      age. In contrast, ikk-beta expression was unchanged over time. We conclude that
      NF-kappaB activity in caudal brainstem is developmentally regulated, and that
      hypoxia-induced NF-kappaB activation is more prominent in youngest rats. We
      postulate that postnatal regulation of NF-kappaB complex expression and function
      may underlie fundamental genomic processes mediating developmental changes in
      neuronal hypoxic tolerance.

PMID- 11335005
TI  - Rat retinal progenitor cells and a retinal pigment epithelial factor.
AB  - Retinal progenitor cells were isolated from explants of neonatal rat retinas and
      characterized by transmission electron microscopy and reverse transcriptase
      polymerase chain reaction and by their response to an isolated retinal pigment
      epithelial cell cell factor. The isolated progenitor cells demonstrated nuclei
      with abundant euchromatin typical of progenitor cells and showed the presence of
      nestin and opsin message. A protein ( approximately 67 kDa) isolated from
      conditioned media of cultured rat RPE cells promoted the survival of isolated
      retinal progenitor cells.

PMID- 11335006
TI  - Hemorrhage following pediatric tonsillectomy before puberty.
AB  - OBJECTIVE: Control of postoperative bleeding, considered as the major
      complication following tonsillectomy, serves as a landmark for the safety of the
      operation. There is a constant decrease of the concentration of hemoglobin during
      childhood with lowest values around 6 years of age with normal values at the
      beginning of puberty accompanied by a constant decrease of the number of
      platelets after birth. Dehydration, poor oral intake and airway problems are
      predominant complications in early childhood. A retrospective study was
      undertaken to evaluate if the incidence of bleeding is associated with certain
      age groups in pediatric patients. We assessed if there is a questionable higher
      risk for blood transfusions due to the age-specific lower hemoglobin
      concentration in children. METHODS: Between January 1988 and August 2000, 2330
      patients under 12 years of age underwent tonsillectomy, with or without
      adenoidectomy, in St. Anna Hospital, Duisburg. Group A (age<6 years) consisted of
      1467 patients of whom 59.6% were male. Group B (aged 6-12 years) consisted of 863
      patients, of whom 48.1% were male. RESULTS: Postoperative bleeding from the
      tonsillar fossae requiring treatment under general anesthesia occurred in group A
      (1%) and B (2.3%). Bleeding from the adenoidectomy site was treated in group A
      (0.3%) and B (0.3%). Primary bleeding occurred in the majority of patients in
      both groups group A (55%) and group B (75%). The latest bleeding was observed 6
      days (group A) and 10 days (group B) following surgery, due to statistical
      analysis the difference was found to be significant (P<0.025). In group A there
      was one 42-month-old boy who died due to massive bleeding despite ligature of the
      external carotid artery and blood transfusions. Statistical evaluation shows a
      significant increase of postoperative bleeding with age (P=0.024). No blood
      transfusion was required in other patients. CONCLUSION: Tonsillectomy can be
      safely performed in children under 6 years of age with no increased risk of
      postoperative bleeding or risk of receiving blood transfusion. Rare cases of
      secondary hemorrhage seem to occur more frequently in younger children and should
      be treated immediately under general anesthesia to avoid severe complications.

PMID- 11335007
TI  - Hearing loss in speech-language delayed children.
AB  - An infant begins to communicate with his/her environment from the first months of
      life. However, true words do not appear until the age of 12-15 months, following
      a rather predictable sequence. Delay or failure of normal language development is
      not a rare situation in childhood and may be due to a variety of reasons. Among
      these, hearing undoubtedly plays a leading part in the language acquisition
      process. The purpose of this study was to assess the percentage of hearing
      impaired children in a group of phenotypically healthy children presenting with
      speech-language delay. Between March 1993 and March 1999, 726 speech-language
      delayed children were examined in our department. In 72 of them, various diseases
      or syndromes had already been diagnosed and so they were excluded from the study.
      The remaining 654 apparently healthy children entered the study and underwent a
      thorough audiological assessment for determination of their hearing thresholds.
      Eighty-seven children (13.3%) showed various degrees of hearing loss. Most of
      them (55 children, 8.4%) suffered from sensorineural hearing impairment, while in
      32 children (4.9%) a conductive hearing loss was discovered. The increased
      prevalence of hearing impairment found in our population mandates a thorough
      hearing evaluation for every case of speech-language delay, even for those
      children who show no evidence of other handicaps. This will help in the early
      diagnosis of hearing loss, allowing proper management to be instituted as early
      as possible.

PMID- 11335008
TI  - The nasal mucosa of children with nocturnal enuresis before and after treatment
      with 1-deamino 8-D-arginine vasopressin spray.
AB  - Intranasal administration of 1-deamino 8-D-arginine vasopressin (DDVAP) used for
      treatment of nocturnal enuresis (NE), might be expected to have various effects
      on the nasal mucosa, e.g. altering the clearance by the mucociliary apparatus. We
      evaluated two samples (brushes) of epithelial surface cells from the nasal
      mucosa, one from each nostril, of 18 children (ten males and eight females) with
      a mean age of 7.7 years (range: 5-13 years) who were affected by primary NE.
      Samples were taken before and 1 and 6 months after administration of DDVAP spray.
      No qualitative changes in the epithelial surface cells from nasal mucosa were
      recognized and only non-statistically significant increases in percentages of
      goblet, ciliated, basal and unciliated cells at 1 and 6 months after therapy were
      observed. Thus, it appears that DDVAP spray can be used for at least 6 months in
      children without apparent risk of damage to the epithelial surface cells from the
      nasal mucosa.

PMID- 11335009
TI  - Temporal bone imaging findings in Waardenburg's syndrome.
AB  - OBJECTIVE: (a) To report computed tomography findings of eight new cases with
      Waardenburg's syndrome (WS) type I and review reported temporal bone radiographic
      and histopathological findings in WS with hearing loss; (b) To determine the
      frequency of inner ear pathologies that may contraindicate cochlear implantation.
      METHODS: A review of 1166 pediatric patients with sensorineural hearing loss
      revealed 12 cases (1%) with WS, whose family screenings disclosed additional 12
      subjects with the same disorder. Among these 24 cases, eight had WS type I and
      were subjected to computed tomography scanning of temporal bone. Imaging findings
      of 28 cases reported previously in English literature were evaluated together
      with our eight patients. RESULTS: Malformation of the inner ear was found in none
      of the nine WS type I cases evaluated here, while the frequency of internal
      acoustic canal malformation was 11%. Regardless of the subtypes of the syndrome,
      6 of 36 cases (17%) had radiological abnormality of the inner ear. Malformation
      and/or absence of the semicircular canals were the most common congenital
      abnormality of the inner ear. Hypoplasia of the cochlea was present in 3 of 36
      cases (8%). CONCLUSIONS: Abnormality of bony labyrinth in WS with congenital
      deafness is not a frequent finding, particularly in WS type I. Therefore, the
      otologist and audiologist must keep in mind that most of these cases are suitable
      for cochlear implantation regarding inner ear anatomy.

PMID- 11335010
TI  - Can nasal endoscopy be used to predict residual symptoms after adenoidectomy for
      nasal obstruction?
AB  - BACKGROUND: the efficacy of adenoidectomy in relieving nasal symptoms has been
      questioned. Although enlarged adenoids are often blamed for nasal obstruction,
      other causes can be missed if examination is not thorough. We suggest that
      endoscopy at the time of adenoidectomy may be useful to confirm large adenoids
      and exclude other causes, and the findings may help predict residual symptoms 2
      years after adenoidectomy. METHOD: a prospective study of a consecutive series of
      children undergoing adenoidectomy for nasal obstruction was performed. All
      underwent endoscopy with a 4-mm rigid endoscope without decongestants under GA
      immediately prior to adenoidectomy. Two years later a postal symptom
      questionnaire was sent, with telephone follow up for non-responders. The findings
      on endoscopy were compared with residual symptoms at 2 years. RESULTS: Forty
      eight children aged 2-9 (mean 4) years were enrolled, 26 of them female. At 2
      years follow up, data were available for 34 children (71%). Complete obstruction
      of the posterior choanae of the nose by adenoids was seen in 21 (62%). Additional
      findings (e.g. septal deviation, hypertrophic mucosa on the turbinates) were
      present in 22 (65%). Of them 9 (26%) had residual nasal symptoms. Of the children
      with less than occlusive adenoids, six (50%) out of 12 had residual symptoms,
      compared with three (14%) out of 21 with occlusive adenoids (chi(2)=4.91,
      P<0.05). Although residual symptoms were more common in those with additional
      findings on the original endoscopy (32 vs. 17%), this did not reach statistical
      significance. CONCLUSIONS: residual nasal symptoms are common when children are
      followed up in the medium term. The findings on endoscopy may predict the success
      of adenoidectomy in relieving the symptoms, and may help to guide further
      treatment.

PMID- 11335011
TI  - Laryngeal oedema caused by accidental ingestion of Oil of Wintergreen.
AB  - Oil of Wintergreen (methyl salicylate) is a common ingredient for liniments,
      ointments and essential oils used in self-treatment of musculoskeletal pain. Its
      pleasant smell also encourages its use to flavour confectionery. The toxic
      potential of this preparation is not always fully appreciated by the general
      public and physicians. To appreciate the danger of this oil it can be compared to
      aspirin tablets (325 mg dose): one teaspoon (5 ml) of Oil of Wintergreen is
      equivalent to approximately 7000 mg of salicylate or 21.7 adult aspirin tablets.
      Ingestion of as little as 4 ml in a child can be fatal. Prevention of accidental
      ingestion of methyl salicylate containing products can be achieved by keeping the
      products out of reach of children, using child resistant bottles, restricting the
      size of the openings of the bottles, appropriate labeling on products and
      reducing the salicylate content. Immediate action should be taken to treat a
      patient with accidental poisoning and hospitalisation is needed for monitoring
      and treatment. The danger of this product should be fully appreciated by both
      physicians and the general public. We present a case of Oil of Wintergreen
      poisoning with development of laryngeal oedema as a complication, general
      information and management issues will also be discussed.

PMID- 11335012
TI  - Recurrent respiratory papillomatosis with esophageal involvement.
AB  - OBJECTIVE: To report a case of recurrent respiratory papillomatosis with diffuse
      involvement of the esophagus in a child. DESIGN: Retrospective case report and
      literature review. SETTING: Tertiary Children's Hospital. CONCLUSION: Endoscopy
      is recommended for detection of esophageal papillomas, especially in patients
      with significant laryngeal lesions or post-cricoid involvement.

PMID- 11335013
TI  - Pyogenic granuloma (lobular capillary hemangioma) of the tongue.
AB  - A patient with a pyogenic granuloma which occurred in an unusual location and at
      an earlier age is presented. Pyogenic granuloma is not an uncommon entity which
      may occur on oral mucosa, face and fingers. The most frequent location
      encountered for oral cavity pyogenic granuloma is the gingiva and the tongue is a
      rare location for its occurrence. These lesions are usually seen between 11 and
      40 years age. Surgical excision and removal of etiological factors are needed for
      treatment.

PMID- 11335014
TI  - Unusual neck mass in an adolescent: benign basal cell adenoma of the minor
      salivary glands of the piriform sinus.
AB  - With an incidence of less than 3%, salivary gland tumors are rare in the head and
      neck. The percentage of basal cell adenomas within the group of salivary gland
      tumors is even less (0.2-2%). Salivary gland tumors occur very rarely in
      adolescents. The basal cell adenoma commonly affects older persons and occurs
      most frequently in the major salivary glands. We present the unusual case of a
      benign basal cell adenoma of the minor salivary glands of the piriform sinus in a
      14 year old male patient. Unusual are the age of the patient, the histological
      type, size and localisation of the tumor.

PMID- 11335015
TI  - Auditory brainstem response and temporal bone pathology findings in a brain-dead
      infant.
AB  - The criteria for assessing adult brain death have been already established, but
      those for infant brain death have not been yet established in Japan. We report
      auditory brainstem response (ABR) and postmortem pathology of the temporal bone
      and brain of a brain-dead 9-month-old female. During the comatose state, her ABR
      showed only waves I and II bilaterally. Autopsy revealed the presence of a left
      cerebellar astrocytoma, herniation and anoxic encephalopathy. The pathological
      examination of the temporal bone revealed the destruction of the inner ear
      particularly on the left side. In the auditory pathway of brain-dead patients,
      degeneration occurs first in the cerebrum, followed by the cochlear nerve. Thus,
      ABR is one of the useful means to assess brain death even in infants.

PMID- 11335016
TI  - Acute airway obstruction from a laryngeal lymphangioma in a child.
AB  - Lymphangiomas present commonly in the head and neck region with over 90% of
      lesions diagnosed before 2 years of age. These lesions have rarely been reported
      as a cause of acute upper airway obstruction and to date, there are very few
      reports in the literature documenting the presence of lymphangiomas in the
      larynx. We present the case of a previously asymptomatic 13-year-old girl with
      Joubert's syndrome, who presented with acute airway obstruction while undergoing
      extubation for a routine dental procedure. Near-complete obstruction of her
      supraglottis from a lymphangioma necessitated tracheotomy to secure the airway.
      The diagnostic work-up and management of this patient and her post-operative
      course are discussed. This case illustrates the insidious presentation of a
      laryngeal lymphangioma and emphasizes the management options for such patients.

PMID- 11335017
TI  - If you would live long, choose your parents well.
AB  - Human longevity appears to have a modest but significant heritable component. A
      recent study in Iceland has added to this evidence by making a unique assessment
      based on records for an entire population. Although the evidence for inheritance
      of human lifespans appears robust, there remains considerable uncertainty about
      the extent of the genetic versus the nongenetic contribution and about the
      importance of gene-environment interactions. Sex-specific patterns of
      transmission of lifespan between parents and offspring might provide clues to the
      basis of lifespan heritability, but the reported patterns are neither conclusive
      nor consistent.

PMID- 11335018
TI  - Plagiarized bacterial genes in the human book of life.
AB  - The initial analysis of the human genome draft sequence reveals that our 'book of
      life' is multi-authored. A small but significant proportion of our genes owes
      their heritage not to antecedent eukaryotes but instead to bacteria. The publicly
      funded Human Genome Project study indicates that about 0.5% of all human genes
      were copied into the genome from bacterial sources. Detailed sequence analyses
      point to these 'horizontal gene transfer' events having occurred relatively
      recently. So how did the human 'book of life' evolve to be a chimaera, part
      animal and part bacterium? And what was the probable evolutionary impact of such
      gene plagiarism?

PMID- 11335019
TI  - Birth and death of duplicated genes in completely sequenced eukaryotes.
AB  - Gene and genome duplications are commonly regarded as being of major evolutionary
      significance. But how often does gene duplication occur? And, once duplicated,
      what are the fates of duplicated genes? How do they contribute to evolution? In a
      recent article, Lynch and Conery analyze divergence between duplicate genes from
      six eukaryotic genomes. They estimate the rate of gene duplication, the rate of
      gene loss after duplication and the strength of selection experienced by
      duplicate genes. They conclude that although the rate of gene duplications is
      high, so is the rate of gene loss, and they argue that gene duplications could be
      a major factor in speciation.

PMID- 11335020
TI  - Bakers yeast rises to the challenge: reconstitution of mammalian steroid receptor
      signalling in S. cerevisiae.
AB  - Steroid hormones are an important class of signalling molecule, regulating a
      diverse range of processes in metazoan eukaryotes. The actions of these hormones
      are mediated by intracellular receptor proteins that act as ligand-activated
      transcription factors. The ability to reconstitute steroid receptor signalling in
      the budding yeast, Saccharomyces cerevisiae, provides a genetically tractable
      model system in which to investigate steroid receptor structure and function.
      Through targeted disruption and genetic screening, an increasing number of genes
      have been identified that are likely to have a role in steroid receptor action.

PMID- 11335021
TI  - Epigenetic analysis of kinetochore assembly on variant human centromeres.
AB  - Human centromere formation involves the assembly of the mitotic kinetochore onto
      chromosomal locations that contain the interphase prekinetochore.
      Immunofluorescent analysis of two functionally converse human centromere
      variants, neocentromeres and inactive centromeres, has been used to evaluate the
      functional significance of over 24 CENTROMERE proteins, providing important
      insight into the epigenetics of centromere formation and kinetochore assembly.

PMID- 11335034
TI  - Purifying selection on silent sites -- a constraint from splicing regulation?

PMID- 11335035
TI  - Genes, models and Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder that is claiming an
      increasing number of victims as the world population ages. The identification of
      gene mutations and polymorphisms that either cause AD or significantly increase
      the risk for developing it enabled the creation of a whole generation of
      realistic rodent models of the disease. Animals expressing mutated human amyloid
      precursor protein and presenilin 1 show dramatic parallels to AD, although none
      of the models appear to capture the full range of pathologies that characterize
      the human disease. Increased refinement of these models will enhance the already
      tantalizing possibility of treatment.

PMID- 11335036
TI  - Molecular phylogenetics: state-of-the-art methods for looking into the past.
AB  - As the amount of molecular sequence data in the public domain grows, so does the
      range of biological topics that it influences through evolutionary
      considerations. In recent years, a number of developments have enabled molecular
      phylogenetic methodology to keep pace. Likelihood-based inferential techniques,
      although controversial in the past, lie at the heart of these new methods and are
      producing the promised advances in the understanding of sequence evolution. They
      allow both a wide variety of phylogenetic inferences from sequence data and
      robust statistical assessment of all results. It cannot remain acceptable to use
      outdated data analysis techniques when superior alternatives exist. Here, we
      discuss the most important and exciting methods currently available to the
      molecular phylogeneticist.

PMID- 11335037
TI  - Establishment of a cellular axis in fission yeast.
AB  - Recent studies in fission yeast Schizosaccharomyces pombe reveal how cells
      establish a cellular axis that specifies domains as the functional 'ends' and
      'middle' of the cell. During interphase, dynamic microtubules position the
      nucleus at the middle of the cell and orientate microtubule 'plus' ends towards
      the ends of the cell. At the cell ends, the microtubule plus ends might establish
      a zone of polarized cell growth and actin assembly by depositing factors such as
      Tea1p. At the cell middle, the nucleus might specify the position of the actin
      contractile ring and the future cell division site by positioning cytokinesis
      factors such as Mid1p.

PMID- 11335038
TI  - Trichothiodystrophy, a transcription syndrome.
AB  - Trichothiodystrophy (TTD) is a rare genetic disorder characterized by a hair
      dysplasia and associated with numerous symptoms affecting mainly organs derived
      from the neuroectoderm. About half of TTD patients exhibit photosensitivity
      because their nucleotide-excision repair pathway (NER) does not remove UV-induced
      DNA lesions efficiently. However, they do not present the skin cancer
      susceptibility expected from such an NER disorder. Their deficiencies result from
      phenotype-specific mutations in either XPB or XPD. These genes encode the
      helicase subunits of TFIIH, a DNA repair factor that is also required for
      transcription of class II genes. Thus, time- and tissue-specific impairments of
      transcription might explain the developmental and neurological symptoms of TTD.
      In a third group of photosensitive patients, TTD-A, no mutation has been
      identified, although TFIIH amount is reduced.

PMID- 11335039
TI  - Chronicles of a switch hunt: gcm genes in development.
AB  - Co-conservation of sequence and function is an important principle during
      evolution. As a consequence, sequence-related genes often have similar functions
      in evolutionarily distant species. Enter the 'glial cells missing' (gcm) genes.
      They code for a small family of novel transcription factors that share DNA
      binding properties and domain structure. However, no evolutionarily conserved
      function is apparent as yet. The prototypical gcm from Drosophila dominates
      nervous system development as a fate switch and master regulator of gliogenesis,
      whereas mammalian gcm genes have roles in placental morphogenesis and development
      of the parathyroid gland. Apparently, structure and function sometimes can go
      separate ways.

PMID- 11335040
TI  - Comparison of source localization of interictal epileptic spike potentials in
      patients estimated by the dipole tracing method with the focus directly recorded
      by the depth electrodes.
AB  - The purpose of the study was to investigate the accuracy of location of
      equivalent current dipoles estimated by the dipole tracing method (DT) utilizing
      a realistic 3-shell (scalp-skull-brain) head model (SSB-DT). Three patients with
      intractable complex partial seizures, diagnosed as having typical temporal
      seizures were investigated. We recorded the interictal spike potentials with
      surface electrodes (International 10/20 system) and with intracerebral depth
      electrodes simultaneously. We compared the location of dipoles of the spikes
      estimated by the SSB-DT with the focus of the spikes determined by the recording
      from the depth electrodes. We found that the location of the dipoles estimated by
      SSB-DT corresponded to the location of the depth electrodes, which could record
      the epileptic spikes. This finding proved that SSB-DT is reliable and valid for
      estimating neural activity in deep locations such as the limbic system.

PMID- 11335041
TI  - Delayed functional recovery by vincristine after sciatic nerve crush injury: a
      mouse model of vincristine neurotoxicity.
AB  - Neuropathy is the dose-limiting side effect of vincristine (VCR) in cancer
      therapy. However, no simple experimental model has yet been reported. Here, we
      present a simple experimental model of VCR neurotoxicity using a mouse sciatic
      nerve crush model, which allows evaluation within a few weeks. VCR administered
      intravenously once on the day after the crush lesion caused a dose-dependent
      delay of the recovery of motor and sensory functions. The minimal dose required
      to cause the delay was 0.25 mg/kg, which corresponded to five times the usual
      clinical dose for man and was far less than the reported doses required to cause
      functional impairment in intact animals. The model would be useful not only for
      the development of new drugs but also for the estimation of the drug interactions
      in combination cancer therapy.

PMID- 11335042
TI  - Increased density of glutamate/N-methyl-D-aspartate receptors in superior
      temporal cortex in schizophrenia.
AB  - Saturable radioligand binding of [(3)H]L-689,560 to the glycine site of the N
      methyl-D-aspartate (NMDA) receptor was determined bilaterally in superior
      temporal cortex (BA22) and prefrontal cortex (BA10) taken post mortem from
      patients with schizophrenia and matched control subjects. A significant increase
      in NMDA receptor density above control values was found bilaterally in BA22 in
      schizophrenia, but not in BA10. The effect was greatest in those patients
      described as primarily type II, in whom the effect was significantly lateralized,
      with a greater elevation in the left hemisphere. A significant decrease in NMDA
      receptor density was found in rat frontal cortex following chronic antipsychotic
      drug administration, indicating that prior drug treatment was unlikely to have
      contributed to the differences in schizophrenia.

PMID- 11335043
TI  - A comparison of the effects of lamotrigine on neuroma-induced action potential
      firing and normal behaviour in rat: implications for establishing a pre-clinical
      'therapeutic index'.
AB  - The effects of lamotrigine on rat neuroma and behavioural paradigms were
      evaluated to determine a pre-clinical therapeutic index. Lamotrigine blocked
      neuroma-induced burst pattern firing at a free plasma concentration of 13.7+/-1.7
      microM (n=5). Oral dosing of lamotrigine (50-200 mg/kg) had no significant
      effects on behaviour but measurements of plasma concentrations of free drug
      showed non-linear oral absorption and lower than predicted drug levels (5-27
      microM). Given intravenously (10-100 mg/kg), lamotrigine did affect behaviour at
      a free plasma concentration of 42.0 microM (n=2). By comparing free plasma
      concentrations, a therapeutic index of 3 was calculated, which is lower than
      published data based on comparing oral doses. We propose that a therapeutic index
      should only be derived with reference to plasma drug concentrations to prevent
      non-linear or incomplete drug absorption from confounding accurate estimation.

PMID- 11335044
TI  - Hypermetabolism in the ventrolateral thalamus in unilateral Parkinsonian resting
      tremor: a positron emission tomography study.
AB  - Tremorogenesis in Parkinson's disease (PD) is assumed to involve a cerebral
      network including the thalamus. An imaging study was performed on eight PD
      patients with strictly unilateral resting tremor using fluorodeoxyglucose
      positron emission tomography coregistered to 3-dimensional magnetic resonance
      imaging. Increased metabolic activity of high statistical significance (P<0.001)
      was found in the anterior ventrolateral nuclear group of the thalamus located
      contralateral to the tremor side. The metabolic changes significantly covaried
      with tremor amplitudes. For the first time, it could be demonstrated that
      thalamic metabolic changes associated with tremor in PD are localized in the
      ventral lateral anterior nucleus (VLa). The results are discussed with respect to
      previous studies on tremor generation.

PMID- 11335045
TI  - Effects of hypothermic deep-anaesthesia on energy metabolism at brain and
      peripheral levels: a multi-probe microdialysis study in free-moving rat.
AB  - Reduction of central energy metabolism is a strategy to protect brain against
      neurotoxic events. The aim of this microdialysis study in rats is to evaluate
      changes in energy metabolite levels at central level (striatum) comparatively to
      peripheral level (subcutaneous adipose tissue) during hypothermic barbituric deep
      anaesthesia (sodium pentobarbital 60 mg/kg intraperitoneally). At brain level,
      extracellular glucose increases (+14.9%) while lactate decreases (-16.6%);
      opposite results were observed at subcutaneous level (-29.2% for glucose and
      +68.3% for lactate). Lactate/pyruvate ratio remains unchanged at brain level, but
      increases at subcutaneous level (+73.5%). In light of previous studies on the
      effects of pentobarbital on regional blood flow and tissue glucose consumption,
      our data correlates the fact that pentobarbital reduces preferentially brain
      energetic metabolism. We suggest that those regional effects are explained, at
      least for a part, by the fact that central isoform glucose transporters (Glut1
      and Glut3) are known to be more sensitive to pentobarbital than peripheral
      isoforms. Such facts can be involved in the protection of brain tissue against
      ischemic risk due to decreased cerebral blood flow decrease.

PMID- 11335046
TI  - Increased response to visual feedback of drug-induced dyskinetic movements in
      advanced Parkinson's disease.
AB  - To investigate the response to visual feedback of involuntary movements which
      have a frequency composition similar to cerebellar tremor but are not caused by
      cerebellar damage, we have tested six advanced Parkinson's disease (PD) patients
      with drug-induced dyskinetic movements using visually guided wrist tracking
      tasks. Tracking performance was assessed under three visual conditions: (1) both
      guiding target and movement cursor were displayed continuously; (2) the target
      display was turned off for the second half of each trial; or (3) the cursor
      display, but not the target, was turned off for the second half of each trial.
      The response to visual feedback of drug-induced dyskinetic movements at 1-5 Hz in
      these advanced PD patients were significantly increased than in normal controls.
      This suggests that increased response to visual feedback might be a common
      feature of low frequency involuntary movements and not directly caused by
      cerebellar damages.

PMID- 11335047
TI  - A narrow window for rescuing cells by the inhibition of calcium influx and the
      importance of influx route in rat cortical neuronal cell death induced by
      glutamate.
AB  - A rescue window for glutamate-insulted cells with regard to Ca(2+) influx was
      first investigated. The addition of EGTA, an impermeable calcium chelator to the
      culture within 5 min after the beginning of glutamate stimulation potently
      suppressed the neuronal cell death examined at 22 h. The effect of EGTA on
      rescuing cells decreased with the time delay of its addition to the system. MK
      801, an antagonist of N-methyl-D-asparate (NMDA) receptor channels also inhibited
      the neuronal cell death in a similar manner to EGTA, suggesting Ca(2+) influx up
      to 5 min after the insult determined the fate of cells. But we also demonstrated
      that the elevated intracellular Ca(2+) did not always induce neurotoxicity. High
      concentration of potassium chloride plus FPL64176, an agonist of L-type Ca(2+)
      channels did not induce neuronal cell death, even though their combination
      elicited equal elevation of intracellular Ca(2+) to that by toxic concentration
      of glutamate, demonstrating that locally elevated intracellular Ca(2+) around
      NMDA receptors is important in the induction of neuronal cell death.

PMID- 11335048
TI  - Acute response of aortic nerve activity to free drop-induced microgravity in
      anesthetized rats.
AB  - To test the hypothesis that arterial baroreflex was stimulated during
      microgravity (microG), arterial pressure (AP), intrathoracic pressure (ITP), and
      aortic nerve activity (ANA) were measured in anesthetized rats during 4.5 s of
      microG produced by free drop. A smooth and immediate reduction in G occurred
      during free drop, microG being achieved 100 ms after the start of the drop. Acute
      microG elicited an immediate and striking, but transient, increase in ANA, with
      no significant change in the AP, but a significant decrease in the end-expiratory
      ITP. The calculated transmural pressure of the aorta increased by 6.9 mmHg 2 s
      after the start of the drop. The increase in ANA lasted 2 s, then ANA returned to
      the control level, despite the calculated end-expiratory transmural pressure
      still being high. These results suggest that microG conditions stimulate the
      aortic baroreceptor by increasing transmural pressure by reducing the ITP.
      However, this effect is only transient, probably due to the high-pass property of
      the baroreceptors.

PMID- 11335049
TI  - Acute and chronic effects of morphine and naloxone on the phosphorylation of
      neurofilament-H proteins in the rat brain.
AB  - Increased amounts of phosphorylated neurofilaments (pNF-H and pNF-M) are found in
      postmortem brains of opioid addicts. Because of the potential relevance of
      aberrant pNF in opioid addiction (alterations of neuronal cytoskeleton and
      associated functions), the effects of opiate drugs on pNF-H were investigated in
      rat brain. Acute morphine (30 mg/kg, 2 h) induced a marked increase in the
      immunodensity of pNF-H in the cerebral cortex (93%). Chronic morphine (10-100
      mg/kg for 5 days) followed by opiate withdrawal resulted in a time-dependent
      decline in pNF-H (induction of tolerance). Thus, 2 h after the last dose of
      morphine, the abundance of pNF-H was still increased (27%), which was followed (6
      24 h) by down-regulation of pNF-H (5% increase at 6 h; 5% decrease at 12 h, and
      29% decrease at 24 h). The acute (10 mg/kg for 2 h) and chronic (2 x 10 mg/kg for
      14 days) treatments with naloxone, an opioid receptor antagonist, did not alter
      pNF-H in the cerebral cortex, suggesting that the opioid receptors (probably the
      mu-type) modulating the phosphorylation state of NF-H are not tonically activated
      by endogenous opioids. The results indicate that morphine addiction is associated
      with an aberrant hyperphophorylation of NF-H in the rat brain.

PMID- 11335050
TI  - Studies on single-strand scissions to cell-free plasmid DNA by the dopaminergic
      neurotoxin 'TaClo' (1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline).
AB  - The DNA-damaging effect of the potent dopaminergic neurotoxin 'TaClo' (1
      trichloromethyl-1,2,3,4-tetrahydro-beta-carboline) is reported. After irradiation
      (300 nm, 350 nm) of cell-free pBR322 DNA in the presence of TaClo, single-strand
      breaks were observed by gel electrophoresis. It seems likely that TaClo undergoes
      a light-induced formation of reactive species (probably radicals). In comparison
      with TaClo, the bromo derivative exhibits an increased toxic action while the
      fluoro derivative shows a weaker effect towards DNA. In the presence of Cu(II) at
      37 degrees C in the dark, DNA strand scissions were found to occur, too. The
      formation of Cu(I), as detected by UV-absorption at 480 nm using the Cu(I)
      complexing ligand BCS, hints at the formation of a reactive species by a
      Cu(II)/Cu(I) mediated redox cycle. Until now, the chemical nature of this
      reactive species has not been elucidated.

PMID- 11335051
TI  - Exercise-induced inflammatory reaction affects electromyographic changes in
      skeletal muscle during dynamic contractions in humans.
AB  - In order to assess the role of exercise-induced inflammatory reactions on
      electromyographic (EMG) changes in humans, we have recorded, during a 3-min
      dynamic handgrip exercise at a high strength (112 w), the surface EMG and the
      compound evoked muscle action potential (M-wave) in control conditions, and this
      after ingestion of a well known cyclooxygenase blocker i.e. acetylsalicylic acid
      (ASA), either as a single dose treatment (10 mg/kg) and as a 3-day treatment (30
      mg/kg per day). The power spectrum density function of EMG allowed us to compute
      both the median frequency (MF) and the energies in a low- and a high-frequency
      band. We estimated the lactic acid concentration from blood samples drawn from an
      antecubital vein and we noted that its production was not affected by ASA (single
      dose or 3-day treatment). We observed at the end of exercise that no change in M
      wave duration and conduction time occurred though the median frequency always
      fell. However, we noted that the slope of the MF vs. time regression line was
      halved after the 3-day ASA treatment which may indicate that inflammatory
      reactions are elicited by exhausting contractions and affect the EMG changes.

PMID- 11335052
TI  - Temporal facilitation of the flexor reflex induced by C-fiber activity:
      comparison between adult and aged rats.
AB  - We investigated the wind-up phenomenon of the flexor reflex in adult and aged
      rats. The sural nerve was stimulated at C-fiber strength and reflex activity was
      recorded from the semitendinosus muscle. The wind-up rate, the increment rate of
      the C-fiber response (i.e. activity from 100 to 600 ms after stimulation) by
      successive stimuli (five train pulses), was decreased exponentially with
      increasing stimulus intervals from 3 to 20 s. The time constant of the decay for
      the aged rats was 9.2+/-3.2 s (mean+/-SD), which was significantly longer than
      for the adult rats (6.4+/-2.9 s). The findings indicate that the effects of C
      fiber activation on the spinal nociceptive pathways attenuate more slowly in aged
      rats as compared with adult rats.

PMID- 11335053
TI  - Reorganization of the uncrossed visual pathways as revealed by Fos-like
      immunoreactivity in rats with neonatal monocular enucleation.
AB  - To elucidate the neuronal characteristics of the functional expansion in the
      uncrossed visual pathways (UXVPs), resulting from early monocular enucleation in
      rats, the feasibility of stimulus-dependent induction of the immediate early gene
      c-fos was examined immunohistochemically. In the UXVPs of rats with monocular
      enucleation at birth, patterned visual stimuli induced Fos-like immunoreactive
      (FLI) neurons much more densely in wide areas of the superficial layer throughout
      the superior colliculus (SC), and in the striate and extrastriate areas of the
      visual cortex (VC). In the UXVPs of rats monocularly enucleated after maturity,
      however, only a few stimulus-dependent FLI neurons were scattered in the
      restricted portions of the SC and the VC.

PMID- 11335054
TI  - Sex differences in the cerebral blood flow response after brief hypercapnia in
      the rat.
AB  - Hypercapnia primarily affects cerebral blood flow (CBF) and not cerebral
      metabolism. We compared the CBF responses due to electrical forepaw stimulation
      before and after brief hypercapnia in male, non-ovarectomized female, and
      ovarectomized female rats. Prior to hypercapnia the CBF responses were similar
      for all three groups. Seven minutes after brief hypercapnic exposure the CBF
      responses to forepaw stimulation were augmented in all groups. However, both 30
      and 60 min after hypercapnia, the magnitude of the CBF responses to forepaw
      stimulation remained elevated for males and ovarectomized females, but not for
      non-ovarectomized females. These results suggest that estrogen may modulate the
      upregulation of the CBF response observed after transient hypercapnia.

PMID- 11335055
TI  - Modulation of pain and hyperalgesia from the urinary tract by algogenic
      conditions of the reproductive organs in women.
AB  - This study investigated the impact of algogenic conditions of the reproductive
      organs upon urinary pain perception in women. A 5-year survey was conducted among
      69 fertile women with calculosis of one upper urinary tract via an ad-hoc
      questionnaire. At both retrospective (3 years) and prospective (2 years)
      investigation, dysmenorrheic women (D) reported more colics than non
      dysmenorrheic women (ND) (P<0.001) and women with previous dysmenorrhea treated
      with estroprogestins (DH)(P<0.05). Pain thresholds (electrical stimulation) of
      the oblique musculature ipsilateral to the stone (L1, site of referred
      hyperalgesia from upper urinary tract) were lower in D than in ND (P<0.01) and DH
      (P<0.05). Calculosis women with asymptomatic endometriosis / ovarian cysts also
      reported more colics (6-month prospective study) and greater threshold lowering
      (P<0.05) than women with calculosis alone. The results show enhancement of
      urinary pain / hyperalgesia by both manifest and latent algogenic conditions of
      the female reproductive organs. This enhancement could derive from neuronal
      sensitization in spinal segments of common projection of the two visceral
      districts (T10-L1).

PMID- 11335056
TI  - The relationship between Abeta-associated free radical generation and Abeta
      fibril formation revealed by negative stain electron microscopy and thioflavine-T
      fluorometric assay.
AB  - In the present study, we investigated whether or not the Abeta peptide itself
      spontaneously generates free radicals using electron spin resonance (ESR)
      spectroscopy while also observing the Abeta fibril formation by negative stain
      electron microscopy. The present results demonstrated a four-line spectrum in the
      presence of Abeta(1-40) with N-tert-butyl-alpha-phenylnitrone (PBN) but not in
      the presence of PBN alone in phosphate-buffered saline. Negative stain electron
      microscopy has shown that Abeta peptides after 96 h of incubation showed more
      amyloid-like fibrils than those after 72 h of incubation while the four-line
      spectrum obtained by ESR spectroscopy attained a maximum intensity after 72 h of
      incubation and thereafter its intensity immediately decreased during the 4-day
      incubation period. These results were also supported by a thioflavine-T (Th-T)
      fluorometric assay. In conclusion, the present results suggest that Abeta
      associated free radical generation is correlated with Abeta fibril formation
      while its generation is only observed transiently during the process of Abeta
      fibril formation.

PMID- 11335057
TI  - Morphine decreases the levels of the gene transcripts of growth hormone receptor
      and growth hormone binding protein in the male rat hippocampus and spinal cord.
AB  - In this study we have characterized the nucleotide sequence of the cDNA for the
      growth hormone receptor (GHR) and examined the effects of morphine on the gene
      transcripts for GHR as well as GH binding protein (GHBP) in the male rat
      hippocampus and spinal cord. Using reverse transcription-polymerase chain
      reaction followed by cloning and sequencing, we found that the entire coding
      region of the GHR mRNA in the spinal cord is identical to that previously
      described in liver. A similar observation was made for the partially sequenced
      GHR cDNA from hippocampus. Northern blot analysis showed that in both tissues the
      levels of the transcripts for both GHR and GHBP were significantly decreased 4 h
      after a single dose of morphine. After 24 h the level of both transcripts did not
      significantly differ from that of control animals. This result indicates that the
      opiate does not only affect the receptor protein as shown earlier by binding
      studies, but also reduces the expression or turnover of the GHR as well as GHBP
      at the transcription level.

PMID- 11335058
TI  - Exposure to bisphenol A during the fetal and suckling periods disrupts sexual
      differentiation of the locus coeruleus and of behavior in the rat.
AB  - This study tested the effect of exposure to bisphenol A (BPA) early in life on
      the sexual differentiation in the brain and behavior in Wistar rats. We
      administered BPA only to mother rats during pregnancy and lactation at a dosage
      of approximately 1.5 mg/kg per day far less than the no-observed-adverse-effect
      level (NOAEL; 50 mg/kg per day). Control female offspring showed a higher
      activity, a lower avoidance memory, and larger locus coeruleus than the male
      controls, while the BPA-exposed group did not show any sexual dimorphism. BPA did
      not affect the reproductive organs or sex hormones. Our results suggest that the
      current methods to determine the NOAEL of artificial industrial chemicals may not
      be sufficient to detect a disruption of the sexual differentiation in the brain.

PMID- 11335059
TI  - Evidence for increased extracellular K(+) as an important mechanism for dorsal
      root induced alternating rhythmic activity in the neonatal rat spinal cord in
      vitro.
AB  - Intracellular recording from rat lumbar motoneurones showed that patterned
      electrical stimulation of one dorsal root induced alternating patterns typical of
      fictive locomotion, accompanied by a reduction in the antidromic spike
      afterhyperpolarization (AHP). Since the AHP depended linearly on extracellular
      K(+) ([K(+)](o)), from the AHP fall we calculated that [K(+)](o) rose to 7.9+/
      0.4 mM, a value within the 7-10 mM range known to elicit fictive locomotion. To
      confirm the specificity of this approach we also tested concentrations of N
      methyl-D-aspartate (2 microM) below threshold for fictive locomotion, and we
      observed that, despite strong excitation, the estimated [K(+)](o) was 6 mM, i.e.
      outside the range for fictive locomotion. We suggest that synaptic activity
      induced by a certain pattern of electrical stimulation of afferent fibres evoked
      persistent elevation in [K(+)](o) which triggered the locomotor network to
      generate rhythmic patterns.

PMID- 11335060
TI  - Differential palmitoylation of two mouse glutamate receptor interacting protein 1
      forms with different N-terminal sequences.
AB  - Glutamate receptor interacting protein (GRIP) is a member of the PDZ domain
      containing protein family that is localized in the postsynaptic density area.
      This protein has been reported to interact specifically with the C-termini of
      AMPA-selective glutamate receptor channel subunits, GluRalpha2 and GluRalpha3
      through its PDZ domains. To clarify the physiological functions of GRIP, we
      cloned mouse GRIP1, and found that there are three sites for alternative splicing
      and two putative translational start codons by characterizing GRIP1 cDNA clones
      and reverse transcription-polymerase chain reaction products. Metabolic labeling
      of COS-7 cells expressing two N-terminal GRIP1 proteins demonstrated that these
      proteins differed in their pattern of palmitoylation. These findings suggested
      that the molecular diversity of GRIP1 underlies the localization and functional
      heterogeneity of this protein.

PMID- 11335061
TI  - Recurrent subthreshold electrical activities of rat neocortical neurons progress
      during long-term culture.
AB  - The properties of neocortical neurons during long-term culture on monolayers of
      astrocytes were examined using whole-cell recording and immunocytochemical
      techniques. The soma size of neocortical neurons became larger and most neurites
      reached neighboring neurons within 2 weeks. Recurrent subthreshold electrical
      activities mediated by synaptic activation were observed at 10 days of culture
      and became more frequent as the neurons grew. Their frequency reached to about 1
      Hz at 4 weeks. While the total number of neurons decreased during culture, the
      ratio of gammaaminobutyric acid (GABA) positive to total (MAP2 positive) neurons
      increased. These results suggest that neurons grown on astrocytes become mature
      during cultivation, and that recurrent subthreshold electrical activities may be
      related to the development of GABAergic inputs.

PMID- 11335062
TI  - Hippocampal damage in rats disrupts decrements in the processing of an intramaze
      landmark in a spatial task.
AB  - Using a four-arm plus-shaped maze, rats with neurotoxic lesions in the dorsal
      hippocampus were trained in a spatial reference memory task in which both the
      extramaze constellation of stimuli and an intramaze landmark (a piece of
      sandpaper covering the floor of the goal) indicated the location of the goal arm.
      After reaching criterion, animals were given two transfer tests in order to
      investigate how much they had learned about the intra and extramaze cues. Results
      showed that during the intramaze transfer, based exclusively on the intramaze
      cue, hippocampal rats produced a performance clearly superior to that of the
      controls. Importantly, the average percentage of correct responses recorded in
      the hippocampal group during the extra versus the intramaze transfer test was
      similar. Thus, no decremental processing of the intramaze cue was detected in the
      lesioned group. In contrast, control rats showed a decremental processing of the
      intramaze landmark performing worse during the intramaze transfer as compared
      with the extramaze transfer. These results support the view that the hippocampus
      regulates decremental changes in the processing of normally irrelevant stimuli,
      extending this claim into a spatial domain.

PMID- 11335063
TI  - Unbiased stereological quantification of neurons in the human spiral ganglion.
AB  - We applied an unbiased stereological technique, the optical fractionator, on five
      human archival temporal bone specimens to estimate the total number of spiral
      ganglion neurons. Available archival human temporal bone specimen has been
      serially sectioned at 20 microm and every tenth section was stained. All the
      stained sections passing through the spiral ganglion were used for the analysis.
      From each section sampled, the counting areas were systematically randomly
      sampled within the sectional area of the spiral ganglion. The neurons within the
      counting areas sampled were counted with the optical disector technique. The
      total number of the human spiral ganglion neurons was estimated by multiplying
      the number of neurons counted by the reciprocal of the aggregate sampling
      fraction. We found an average of 41700 neurons with a coefficient of variation of
      0.14, which is a significant departure from the previously published data
      obtained with the assumption-based methods. The mean coefficient of error for the
      stereological estimates of the total number of human spiral ganglion neurons was
      0.078. The present report presents unbiased stereological sampling and counting
      strategies for the future quantitative studies on the spiral ganglion neurons.
      The result of the present study provides the first unbiased baseline value of the
      human spiral ganglion neurons.

PMID- 11335064
TI  - Nicotinic acetylcholine receptor ligands differently affect cytochrome oxidase in
      the Honeybee brain.
AB  - The objective of this study was to determine if nicotinic receptor antagonists
      known for their ability to impair memory in the honeybee could induce changes in
      brain metabolism. We tested the effect of antagonists [hexamethonium,
      mecamylamine, alpha-bungarotoxin (alpha-BTX)] and agonist (nicotine) brain
      injections on cytochrome oxidase (CO) histochemistry. Within as little as 30 min
      following nicotine injection, an increase of the staining was observed in almost
      all the structures analyzed. The increase was limited to the alpha-lobe after
      alpha-BTX injection. In contrast, the antagonists hexamethonium and mecamylamine
      reduced CO staining in this structure that seems to be involved in information
      retrieval. These results suggest that the decrease of metabolism in the alpha
      lobe obtained with hexamethonium and mecamylamine injections could be related to
      the impairment of retrieval processes previously observed with these drugs.

PMID- 11335065
TI  - Amyloid beta protein 1-40 and 1-42 levels in matched cerebrospinal fluid and
      plasma from patients with Alzheimer disease.
AB  - We quantitated amyloid beta proteins 1-40 (Abeta40) and 1-42 (Abeta42), and
      alpha1- antichymotrypsin (ACT) in matched cerebrospinal fluid (CSF) and plasma of
      50 patients with probable Alzheimer disease, and analyzed the relationships with
      age, sex, Mini-Mental State Examination (MMSE), and apolipoprotein E phenotype.
      There was no relation between CSF Abeta40 and Abeta42 levels with those of
      plasma. CSF and plasma Abeta40 and Abeta42 levels showed no association with age,
      sex, and MMSE score. There was a significant correlation between CSF ACT and
      plasma ACT levels. The data suggest that plasma ACT crosses the blood-brain
      barrier. However, a lack of correlation between CSF Abeta40 and Abeta42 levels
      with those of plasma suggests that Abeta in CSF and plasma originates from
      different sources.

PMID- 11335066
TI  - Polyamines in the basal ganglia of human brain. Influence of aging and
      degenerative movement disorders.
AB  - The distribution of polyamines in the human basal ganglia was examined, using
      dansyl-derivatives and high pressure liquid chromatography with fluorimetric
      detection. A heterogeneous distribution of putrescine, spermidine (SD) and
      spermine (SM) was observed in control brains. A consistent negative correlation
      between SD and SM content and age was found in different brain areas. These
      results suggest an involvement of polyamines in age-related changes occurring in
      white-matter. When the influence of degenerative movement disorders -Parkinson's
      disease, Huntington's disease (HD) and progressive supranuclear palsy- was
      analyzed, significant changes were observed only in HD, where a decrease in the
      concentration of SM was found in the putamen. These results suggest that in
      advanced stages of neurodegenerative processes, polyamines maintain their
      regulation. Only in the presence of severe atrophy, SM concentration is reduced.

PMID- 11335067
TI  - Real-time multisite observation of glutamate release in rat hippocampal slices.
AB  - A multichannel glutamate sensor was fabricated that consists of enzyme modified
      electrodes and has a high sensitivity and selectivity to glutamate. We placed a
      rat hippocampal slice on the sensor and monitored the current at four electrodes
      resulting from the stimulation with muscimol, a gamma-aminobutyric acid(A)
      (GABA(A)) receptor agonist. We obtained different glutamate concentration
      increases at the different positions, suppressed by bicuculline, a GABA(A)
      receptor antagonist. This demonstrated that the sensor can monitor the glutamate
      released via GABA(A) receptors pathways, and the difference in the concentrations
      may indicate differences in the distribution of GABA(A) receptor as well as
      diverse receptor functions. This multichannel sensor may be useful for non
      invasive, real-time monitoring of glutamate distribution, which would make it a
      valuable tool for pharmacological analysis.

PMID- 11335068
TI  - Attention-deficit disorder in adults with or without hyperactivity: where is the
      difference? A study in humans using short echo (1)H-magnetic resonance
      spectroscopy.
AB  - The DSM-IV distinguishes three subtypes of attention deficit hyperactivity
      disorder: The predominantly inattentive subtype (ADD), the hyperactive-impulsive
      subtype (ADHD) and the combined subtype. We used short echo time (1)H-magnetic
      resonance spectroscopy (TE=30 ms, TR=3000 ms) for absolute quantification of
      neurometabolites using the LC model algorithm to investigate a possible metabolic
      neuropathology in adult patients with ADD and ADHD and compared their spectra
      with healthy controls (n=5 in each group). Spectra were acquired in the left
      dorsolateral prefrontal cortex and the left striatum. There was a significant
      group difference in N-acetylaspartate (NAA) concentration in the left
      dorsolateral prefrontal cortex distinguishing patients with the ADHD from
      patients with pure ADD and healthy controls. The absolute NAA concentration was
      significantly reduced only in the ADHD group. Since NAA-depletion reflects a
      state of neuronal dysfunction, this finding indicates evidence of subtle left
      prefrontal neuropathology in ADHD in adults.

PMID- 11335069
TI  - Adaptive changes in withdrawal reflexes after noxious stimulation at the heel and
      the toes in the decerebrated rabbit.
AB  - In decerebrated rabbits, reflexes evoked by electrical stimulation of the toes in
      the ankle flexor tibialis anterior were enhanced for > 30 min after application
      of 20% mustard oil to the base of the toes, whereas responses of the ankle
      extensor medial gastrocnemius to stimulation of the heel were depressed for > 20
      min by the same stimulus. Applied to the heel, mustard oil had inconsistent
      effects on the flexor reflex but potentiated the extensor response for
      approximately 1 h. Intrathecal co-administration of naloxone (25 microg) with the
      selective alpha(2)-adrenoceptor antagonist RX 821002 (200 microg) enhanced both
      reflexes to more than twice pre-drug values and reduced or abolished all effects
      of mustard oil. These data confirm that the location of a noxious stimulus is an
      important determinant of the subsequent adaptive changes in reflexes, and
      indicate roles for endogenous opioids and noradrenaline in these processes.

PMID- 11335070
TI  - Glufosinate ammonium induces convulsion through N-methyl-D-aspartate receptors in
      mice.
AB  - Glufosinate ammonium, a broad-spectrum herbicide, causes convulsion in rodents
      and humans. Because of the structural similarities between glufosinate and
      glutamate, the convulsion induced by glufosinate ammonium may be ascribed to
      glutamate receptor activation. Three N-methyl-D-asparate (NMDA) receptor
      antagonists, dizocilpine, LY235959, and Compound 40, and an alpha-amino-3-hydroxy
      5-methylisoxazole-4-propionic acid (AMPA)/kainate receptor antagonist, NBQX, were
      coadministrated with glufosinate ammonium (80 mg/kg, intraperitoneally) in mice.
      Statistical analyses showed that the NMDA receptor antagonists markedly inhibited
      the convulsions, while the AMPA/kainate receptor antagonist had no effect on the
      convulsion. These results suggest that the convulsion caused by glufosinate
      ammonium is mediated through NMDA receptors.

PMID- 11335071
TI  - Differential vulnerability of basal and apical hair cells is based on intrinsic
      susceptibility to free radicals.
AB  - The base of the cochlea is more vulnerable to trauma than the apex as seen in the
      pattern of hair cell damage by cisplatin or aminoglycosides. The differential
      vulnerability is maintained in organotypic cultures exposed directly to these
      drugs, suggesting there may be an intrinsic difference in sensitivity to damage
      along the cochlear spiral. We therefore investigated the survival capacity of
      isolated outer hair cells and strips dissected from different turns of the guinea
      pig organ of Corti in short-term culture. Cells were stained with fluorescent
      indicators of viable or dead cells, calcein-AM and ethidium homodimer. After 5 h
      at room temperature, up to 90% of outer hair cells from the apex survived, but
      less than 30% from the base. In contrast, basal inner hair cells remained viable,
      and supporting cells survived for at least 20 h. The difference in survival
      capacity between basal and apical outer hair cells coincided with a significantly
      lower level of the antioxidant glutathione in basal outer hair cells compared
      with apical outer hair cells. This suggested that basal outer hair cells may be
      more vulnerable to free-radical damage than apical outer hair cells. The survival
      of basal outer hair cells was significantly improved by addition of the radical
      scavengers n-acetyl cysteine, p-phenylenediamine, glutathione, mannitol or
      salicylate. The protection by antioxidants implies that the accelerated death of
      basal outer hair cells is due to free-radical damage. The results support an
      intrinsic susceptibility to free radicals that differs among cochlear cell
      populations. This differential provides a rational explanation for base-to-apex
      gradients observed in various forms of cochlear pathology.

PMID- 11335073
TI  - Amplitude of distortion product otoacoustic emissions in the guinea pig in f(1)-
      and f(2)-sweep paradigms.
AB  - The amplitude versus frequency relations of distortion product otoacoustic
      emissions (DPOAEs) were studied in the guinea pig, using both the f(1)- and the
      f(2)-sweep paradigms to vary the primary frequency separation. The amplitude of
      the DPOAEs 2f(1)-f(2), 3f(1)-2f(2), 4f(1)-3f(2), and 2f(2)-f(1), plotted as a
      function of DP frequency, exhibited a bandpass structure. The separation of the
      primaries for which the DPOAE level is maximum is referred to as the optimum
      ratio f(2)/f(1). For the lower sideband DPOAEs (f(dp)<f(1), f(2)), the optimum
      ratio varies non-monotonically with the primary frequency region. At an f(2)
      around 4.4 kHz, the optimum ratio for 2f(1)-f(2) reaches a maximum of about 1.46
      while elsewhere it is in the more commonly found 1.2-1.3 range. The width of the
      amplitude profiles was studied by determining their Q(10 dB). The f(2)-sweep
      yielded significantly larger Q(10 dB) than f(1)-sweep, for the lower sideband
      DPOAEs. The amplitude versus frequency functions of the lower sideband DPOAEs
      approximately line up. Upon closer inspection, however, with f(1)-sweep the 2f(1)
      f(2) DPOAE has its maximum at a slightly smaller DP frequency than the higher
      order DPOAEs. With f(2)-sweep, on the contrary, the 2f(1)-f(2) tends to peak at a
      higher DP frequency than the other lower sideband distortion products. When the
      amplitude is considered as a function of the ratio between f(dp) and f(2), the
      difference between f(1)- and f(2)-sweep with respect to the width and the
      alignment of the amplitude functions disappears. The amplitude profiles of the
      lower sideband DPOAEs are a function of the DPOAE frequency f(dp) relative to
      f(2).

PMID- 11335072
TI  - Aldosterone and prednisolone control of cochlear function in MRL/MpJ-Fas(lpr)
      autoimmune mice.
AB  - Recently this laboratory showed aldosterone, a mineralocorticoid that only
      enhances sodium transport, was as effective as the glucocorticoid prednisolone in
      restoring cochlear function in autoimmune mice. To further test this relationship
      between sodium transport and autoimmune hearing loss, dosage comparisons were
      made of prednisolone and aldosterone control of the auditory dysfunction in
      autoimmune MRL/MpJ-Fas(lpr) mice. Mice were tested at 2 months of age to
      establish baseline auditory brainstem response (ABR) thresholds, hematocrit,
      serum immune complexes, and anti-nuclear antibodies. Mice were then given
      different doses of prednisolone or aldosterone in their drinking water for 2
      months. After the treatment period, most untreated water controls showed
      elevation of ABR thresholds due to the ongoing autoimmune disease. However, the
      steroid groups had significantly more mice with improved or unchanged thresholds.
      Both steroids improved stria vascularis morphology, although aldosterone appeared
      to be more effective. The immune suppressive prednisolone caused a dose-related
      improvement in levels of serum immune complexes and hematocrit, hallmarks of
      systemic autoimmune disease. Aldosterone, which has no immune suppressive
      function, did not alter systemic disease. The comparable efficacy of prednisolone
      and aldosterone in restoring auditory function suggests steroid reversal of
      autoimmune hearing loss in mice is due to increasing stria vascularis sodium
      transport and not suppression of systemic autoimmune reactions.

PMID- 11335074
TI  - Susceptibility to noise exposure during postnatal development in rats.
AB  - Susceptibility to noise-induced hearing loss was studied during maturation in 20
      female pigmented rats (strain Long-Evans). Young rats, 3, 4, 5 and 6-7 weeks old,
      were exposed for 1 h to a broad-band noise with an intensity of 120 dB SPL. The
      thresholds and amplitudes of middle latency responses (MLR) recorded from
      electrodes implanted on the surface of the auditory cortex were analyzed before
      and after noise exposure. The results were compared with data from our previous
      study, in which the effects of broad-band noise exposure on MLR were investigated
      in adult rats [Syka, J. and Rybalko, N. (2000) Hear. Res. 139, 59-68]. The
      hearing thresholds of 3-7 week old rats before noise exposure were within the
      normal adult range. Noise exposure in young rats produced an adult-like pattern
      with an elevation of hearing thresholds. One-two weeks post-exposure a recovery
      of MLR thresholds was observed, though full recovery only occurred in the low
      frequency range. Recovery of hearing thresholds in the high frequency range
      depended on the age of the animal at the time of exposure. In all animals aged
      less that 6-7 weeks, exposure resulted in a permanent threshold shift in the
      range of 4-32 kHz. The mean values of permanent threshold shifts at 16 kHz (the
      frequency of maximal hearing loss) were 53.0+/-4.5, 47.6+/-9.6, 37.5+/-7.5 and
      27+/-10 dB for rats exposed at 3, 4, 5 and 6-7 weeks of age, respectively.
      Similar to adult rats, young rats exposed to noise exhibited an enhancement of
      MLR amplitudes. This amplitude enhancement was more pronounced in the high
      frequency range. In several rats exposed at 3-5 weeks of age, the recovery period
      to normal amplitudes was substantially prolonged and lasted 4-8 weeks in
      comparison with 1-2 weeks in adult rats. These results demonstrate a greater
      susceptibility to noise exposure in rats during the first 5 postnatal weeks.

PMID- 11335075
TI  - The influence of external and internal noise on the detection of increments and
      decrements in the level of sinusoids.
AB  - This paper examines the influence of external and internal noise on the detection
      of increments and decrements in the level of sinusoidal pedestals. In experiment
      1, the pedestals were presented either 18 dB above the masked threshold in
      broadband noise (condition 18-Masked) or 18 dB above the absolute threshold
      (condition 18-Abs). Pedestal frequencies were 250, 1000 or 4000 Hz, and
      increment/decrement durations ranged from 5 to 200 ms. For condition 18-Masked,
      thresholds decreased with increasing pedestal frequency, while for condition 18
      Abs, thresholds did not change significantly with pedestal frequency. These
      results are consistent with the idea that, in condition 18-Masked, thresholds
      were influenced by the inherent fluctuations produced by the background noise at
      the output of the auditory filter centred at the pedestal frequency. These
      fluctuations would decrease in rate with decreasing centre frequency, and this
      might have a greater deleterious effect on performance. In contrast, the
      characteristics of the internal noise that presumably limited performance in
      condition 18-Abs do not appear to vary with pedestal frequency. In experiment 2,
      a 4000 Hz pedestal was used. It was presented either in quiet or in the presence
      of narrowband noise centred at 4000, or 7000 Hz, or both. The noise bandwidth
      ranged from 50 to 400 Hz. The increment/decrement duration ranged from 5 to 100
      ms. The noise centred at 7000 Hz produced only a small deterioration in
      performance relative to that measured in quiet. The noise centred at 4000 Hz had
      a larger effect, and the effect increased with decreasing noise bandwidth. This
      is consistent with the idea that slow fluctuations at the output of the auditory
      filter impair increment and decrement detection more than rapid fluctuations. A
      model is proposed to account for the results, based on a simulated auditory
      filter, a compressive non-linearity, a sliding temporal integrator, a logarithmic
      transform and a template mechanism. Analysis using the model suggests that the
      effect of centre frequency observed in experiment 1, when background noise was
      present, cannot be explained entirely in terms of the fluctuations produced by
      the background noise at the output of the auditory filter centred at the pedestal
      frequency.

PMID- 11335076
TI  - The expression of fibroblast growth factors and their receptors in the embryonic
      and neonatal mouse inner ear.
AB  - Four different fibroblast growth factor receptors (FGFR) are known, three of
      which have splice variants (known as the b and c variants) in the FGF-binding
      domain, to give different patterns of sensitivity to the different FGFs. The
      expression of the b and c variants of the FGF receptors, together with the
      expression of the ligands FGF1, FGF2, FGF3, FGF7, FGF8b and FGF8c, was determined
      by quantitative reverse transcription-polymerase chain reaction in developing
      whole mouse inner ears, and in dissected components of the postnatal mouse inner
      ear. At embryonic age (E)10.5 days, when the otocyst is a simple closed sac, the
      receptor most heavily expressed was FGFR2b, relative to the postnatal day 0
      level. Over the period E10.5-E12.5, during which the structures of the inner ear
      start to form, the expression of the different FGF receptors increased 10(2)
      10(4) fold per unit of tissue, and there was a gradual switch towards expression
      of the 'c' splice variants of FGFR2 and FGFR3 rather than the 'b' variants. At
      E10.5, the ligands most heavily expressed, relative to the postnatal day 0 level,
      were FGF3, FGF8b and FGF8c. In the postnatal inner ear, the patterns of
      expression of receptors and ligands tended to be correlated, such that receptor
      variants were expressed in the same regions as the ligands that are known to
      activate them effectively. The neural/sensory region expressed high levels of
      FGFR3c, and high levels of the ligand FGF8b. The same area also expressed high
      levels of FGFR1b and FGFR2b, and high levels of FGF3. The lateral wall of the
      cochlea (including the stria vascularis and the spiral ligament) expressed high
      levels of FGFR1c and FGF2. It is suggested that the different FGF receptors and
      ligands are expressed in a spatially coordinated pattern, to selectively program
      cochlear development.

PMID- 11335077
TI  - Psychophysics of a prototype peri-modiolar cochlear implant electrode array.
AB  - Psychophysical measurements were performed in three hearing-impaired adult
      subjects implanted with a CI22 cochlear prosthesis (Cochlear Ltd.) fitted with a
      developmental peri-modiolar electrode array. The array was manufactured with a
      curvature approximating that of the inner wall of the scala tympani but, after
      straightening and insertion, lay on average about half way between the inner and
      outer walls of the scala. All subjects were tested with bipolar stimulation; two
      were also tested with monopolar, employing the most basal electrode as the
      return. Maximum comfortable level and threshold reduced with decreasing distance
      of electrode from the modiolus, whereas dynamic range increased. The linearity of
      the loudness growth function did not vary significantly with electrode position
      but the function was more non-linear for lower maximum comfortable levels.
      Current level discrimination, normalized with respect to dynamic range, improved
      with decreasing distance of electrode from the modiolus in two subjects. Pitch
      varied regularly with insertion depth of the stimulated electrode for bipolar
      stimulation in two subjects and also for monopolar stimulation in one subject.
      Electrode discrimination was enhanced by closeness to the modiolus. Whereas the
      forward masking patterns for bipolar stimulation of electrodes close to the
      modiolus had a sharp double-peaked structure, those for monopolar stimulation
      were flatter and had a single peak.

PMID- 11335078
TI  - Genetic basis for susceptibility to noise-induced hearing loss in mice.
AB  - The C57BL/6J (B6) and DBA/2J (D2) inbred strains of mice exhibit an age-related
      hearing loss (AHL) due to a recessive gene (Ahl) that maps to Chromosome 10. The
      Ahl gene is also implicated in the susceptibility to noise-induced hearing loss
      (NIHL). The B6 mice (Ahl/Ahl) are more susceptible to NIHL than the CBA/CaJ (CB)
      mice (+(Ahl)). The B6xD2.F(1) hybrid mice (Ahl/Ahl) are more susceptible to NIHL
      than the CBxB6.F(1) mice (+/Ahl) [Erway et al., 1996. Hear. Res. 93, 181-187].
      These genetic effects implicate the Ahl gene as contributing to NIHL
      susceptibility. The present study demonstrates segregation for the putative Ahl
      gene and mapping of such a gene to Chromosome 10, consistent with other
      independent mapping of Ahl for AHL in 10 strains of mice [Johnson et al., 2000.
      Genomics 70, 171-180]. The present study was based on a conventional cross
      between two inbred strains, CBxB6.F(1) backcrossed to B6 with segregation for the
      putative +/Ahl:Ahl/Ahl. These backcross progeny were exposed to 110 dB SPL noise
      for 8 h. All of the progeny were tested for auditory evoked brainstem responses
      and analyzed for any significant permanent threshold shift of NIHL. Cluster
      analyses were used to distinguish the two putative genotypes, the least affected
      with NIHL (+/Ahl) and most affected with PTS (Ahl/Ahl). Approximately 1/2 of the
      backcross progeny exhibited PTS, particularly at 16 kHz. These mice were
      genotyped for two D10Mit markers. Quantitative trait loci analyses (log of the
      odds=15) indicated association of the genetic factor within a few centiMorgan of
      the best evidence for Ahl [Johnson et al., 2000. Genomics 70, 171-180]. All of
      the available evidence supports a role for the Ahl gene in both AHL and NIHL
      among these strains of mice.

PMID- 11335079
TI  - Cochlear nerve acoustic envelope response detection is improved by the addition
      of random-phased tonal stimuli.
AB  - We test Lowenstein's dc bias hypothesis as an alternative mechanism for the
      phenomenon sometimes called 'stochastic resonance'. Probe stimuli consisting of
      paired phase-locked tones at frequencies f(1) and f(2) (where f(2)-f(1)=800 Hz,
      f(1)>4.5 kHz) and at equal intensity were used to generate synchronous 800 Hz
      cochlear nerve activity (envelope responses). When a background tone of the same
      intensity, with a frequency halfway between f(1) and f(2), is presented
      simultaneously with the probe stimulus, the envelope response amplitude typically
      decreases. Consistent with Lowenstein's hypothesis, however, when the intensities
      of the probe and background tone are near the detection threshold of the envelope
      response (approximately 0-20 dB sound pressure level), the simultaneous presence
      of the background tone often increases the amplitude of the envelope response. At
      these same intensity levels, when the background tone precedes the probe
      stimulus, it decreases the amplitude of the response to the probe stimulus. The
      effects of simultaneous presentation of the probe and the background tone are
      frequency-dependent, becoming less pronounced or reversing as the frequency of
      the background tone departs from those of the probe stimuli.

PMID- 11335080
TI  - Three-dimensional and ultrastructural relationships between intermediate cells
      and capillaries in the gerbil stria vascularis.
AB  - Structural relationships between intermediate cells and capillaries in the stria
      vascularis of gerbils were examined by confocal laser microscopy and electron
      microscopy. Immunostaining for an inward rectifier K(+) channel (Kir4.1), which
      was localized to intermediate cells, was used to determine the three-dimensional
      distribution of intermediate cells. These cells constituted a honeycomb-like
      network, and their dendritic processes surrounded not only capillaries but also
      the basolateral surface of epithelial marginal cells. On the basis of the above
      finding and the large K(+) conductance in intermediate cells, we propose that the
      network composed of intermediate cells has a spatial K(+) buffering function.
      Transmission electron microscopy revealed the absence of the basal lamina in some
      regions and the presence of a gap junction-like membrane association between
      intermediate cells and pericytes and/or endothelial cells. This result supported
      our previous finding that intermediate cells were dye-coupled with pericytes and
      endothelial cells. The presence of gap junctions between intermediate cells and
      pericytes and/or endothelial cells suggests that endothelial cells and pericytes
      may play roles other than forming a structural route for blood circulation.

PMID- 11335081
TI  - Frequency organization and cellular lamination in the medial geniculate body of
      the rabbit.
AB  - Cellular laminae within the tonotopically organized ventral division of the
      medial geniculate body (MGV) of the cat have been proposed as the anatomical
      substrate for physiologically defined isofrequency contours. In most species, the
      laminae are not visible with routine Nissl stains, but are defined by the
      dendritic fields of principal cells and the terminal arbors of afferents arising
      from the inferior colliculus. In the present study, we have used the rabbit to
      directly examine the relationship between the laminar and tonotopic organization
      of the MGV. Best frequency maps of the MGV in anesthetized adult New Zealand
      white rabbits were generated from cluster responses recorded at 30-100 microm
      intervals to randomly presented tone bursts. Parallel vertical penetrations,
      roughly perpendicular to the laminae, revealed a low-to-high frequency gradient
      within the MGV. Non-laminated regions of the ventral division, generally found at
      the rostral or caudal poles, did not demonstrate a systematic frequency gradient.
      In contrast to a predicted smooth gradient, best frequencies shifted in discrete
      steps across the axis of the laminae. A similar step-wise frequency gradient has
      been shown in the central nucleus of the inferior colliculus of the cat. It is
      proposed that the central laminated core of the MGV represents an efficient
      architecture for creating narrow frequency filters involved in fine spectral
      analysis.

PMID- 11335082
TI  - Effects of conductive hearing loss on gerbil central auditory system activity in
      silence.
AB  - Animal models of conductive hearing loss (CHL) show altered structure and
      function in the central auditory system (CAS), particularly following unilateral
      deprivation. Assessment of neuronal activity as measured by 2-deoxyglucose (2-DG)
      uptake following CHL has been reported by two groups of investigators, with
      different findings. Woolf and colleagues [Brain Res. 274 (1983) 119] found that 2
      DG uptake increased in the cochlear nucleus ipsilateral to the CHL, while Tucci
      et al. [Laryngoscope 109 (1999) 1359] found a decrease in 2-DG uptake in the
      ipsilateral cochlear nucleus. One significant difference between the protocols in
      the two studies was that, in the first study, animals were maintained in silence
      following 2-DG injection, whereas in the Tucci et al. study, animals were exposed
      to sound. The current study was designed to replicate the protocol used by Woolf
      et al. Young adult gerbils underwent unilateral malleus removal with bilateral
      canal ligation (n=6) or a sham procedure (n=7) 48 h prior to 2-DG administration
      and sacrifice. Optical density measurements were made from CAS nuclei. 2-DG
      uptake decreased in the ipsilateral cochlear nucleus and contralateral inferior
      colliculus, and in nuclei of the superior olivary complex bilaterally, supporting
      the finding that CHL is associated with a decrease in CAS neuronal activity.

PMID- 11335083
TI  - Sensitivity of unanesthetized chinchilla auditory system to noise burst onset,
      and the effects of carboplatin.
AB  - The gross near-field responses of the auditory nerve and inferior colliculus to
      noise burst stimuli were recorded through intracranially implanted electrodes in
      six unanesthetized chinchillas. Responses were studied as a function of stimulus
      plateau amplitude and rise time, both before and after a systemic dose of 75
      mg/kg of carboplatin. Both recording sites showed sensitivity to stimulus level
      and rise time. Increases in stimulus level and decreases in stimulus rise time
      each produced increases in the response magnitude, and decreases in response
      latency. When the stimuli were re-specified as rate of pressure change at sound
      onset (Pa/s), the amplitude and latency of responses at each site were found to
      be a direct function of rate of sound pressure change. These data provide the
      first confirmation in unanesthetized animals of previous single unit observations
      in barbiturate-anesthetized cats. Carboplatin treatment resulted in a 20-80% loss
      of inner hair cells, a modest threshold elevation, and a 50-75% reduction in peak
      response amplitudes. The general patterns of sensitivity to stimulus level and
      rise time were not markedly affected by carboplatin, nor was the fashion in which
      response parameters (amplitude and latency) were ruled by rate of pressure change
      at sound onset.

PMID- 11335084
TI  - Glial cell line-derived neurotrophic factor (GDNF) and its receptor complex are
      expressed in the auditory nerve of the mature rat cochlea.
AB  - Glial cell line-derived neurotrophic factor (GDNF) is a survival factor for many
      neuronal cell types which signals through a heterodimer receptor consisting of
      GDNF-family receptor alpha 1 (GFRalpha-1) and Ret (rearranged during
      transformation). GDNF expression has previously been reported in the inner hair
      cells of the rat cochlea, with expression of GFRalpha-1 but not Ret in the cell
      bodies of the auditory nerve (spiral ganglion cells), using in situ
      hybridization. The present study used reverse transcription-polymerase chain
      reaction (RT-PCR), and immunocytochemistry to examine GDNF, GFRalpha-1 and Ret in
      the adult rat auditory nerve. Semi-quantitative RT-PCR showed expression of GDNF
      and the two receptor components, GFRalpha-1 and Ret, in the modiolar subfraction
      of the cochlea containing spiral ganglion cells. A shorter mRNA splice variant
      for GDNF was also detected. Immunocytochemistry showed immunostaining in the
      modiolus for GDNF, GFRalpha-1 and Ret that was confined to spiral ganglion cells.
      When RT-PCR expression levels were compared to the expression in the substantia
      nigra, GFRalpha-1 expression levels were similar, Ret mRNA was lower in the
      modiolus and GDNF expression was higher in the modiolus. However, when GDNF was
      further assessed using Western blot, while GDNF protein was found in the modiolus
      it was at lower levels than in substantia nigra tissue. These results demonstrate
      that GDNF and both of its receptor components are found in spiral ganglion cells
      of the adult rat cochlea. Along with the previous report of GDNF in inner hair
      cells, these new results provide a basis for the role of GDNF as a survival
      factor for the auditory nerve, as suggested by previous studies.

PMID- 11335085
TI  - Co-existence of tyrosine hydroxylase and calcitonin gene-related peptide in
      cochlear spiral modiolar artery of guinea pigs.
AB  - The distribution of tyrosine hydroxylase (TH) and calcitonin gene-related peptide
      (CGRP) on the cochlear spiral modiolar artery (SMA) was investigated in the
      guinea pig. The SMA was dissected from the modiolus so that the entire length of
      the vessel and many of its branches could be observed. Immunohistochemical
      labeling and double immunofluorescence were employed to localize each compound
      and to determine whether the TH and CGRP co-exist in neurons of the SMA.
      Microscopic examination of whole vessel preparations revealed numerous TH- and
      CGRP-positive neural networks innervating the SMA and its branches. The labeled
      neurons showed distinct arborization, varicosities and overlap, and were of
      different diameters. Confocal immunofluorescence microscopy of double-labeled TH
      and CGRP neurons showed that a number of the TH- and CGRP-positive neurons were
      co-labeled. Thus, TH and CGRP partially co-exist within the neuronal innervation
      of SMA. These findings support a hypothesis that specific neuropeptide and
      adrenergic neurons regulate cochlear blood flow.

PMID- 11335086
TI  - Expression of mRNA encoding extracellular matrix glycoproteins SPARC and SC1 is
      temporally and spatially regulated in the developing cochlea of the rat inner
      ear.
AB  - SPARC is a multifunctional extracellular matrix (ECM) glycoprotein that shares
      partial sequence homology with SC1/hevin. These ECM molecules exhibit calcium
      binding properties and modulate cellular interactions. This study examines the
      expression of SC1 and SPARC mRNA in the developing cochlea of the rat inner ear
      prior to and after the onset of hearing. At all ages examined, SC1 mRNA is highly
      expressed in neurons of the spiral ganglion. In contrast, SPARC transcripts are
      not detected in the spiral ganglion but are enriched in the temporal bone and
      cartilaginous otic capsule surrounding the cochlea. Both SC1 and SPARC mRNA are
      expressed in connective tissue elements involved in maintaining ionic homeostasis
      of cochlear fluids. SC1 mRNA is localized to type III fibrocytes of the spiral
      ligament (slg) and marginal cells of the stria vascularis, while SPARC mRNA is
      apparent in the spiral limbus and type I fibrocytes of the slg. At postnatal day
      10, SPARC mRNA shows a dramatic change in expression. High levels of SPARC
      transcripts are induced in Deiters cells (dc) of the organ of Corti.
      Interestingly, this induction of SPARC mRNA correlates with the onset of hearing.
      This suggests that SPARC may play a role in calcium regulation in dc when
      functional maturation of the cochlea is attained and rapid changes in calcium
      levels are required.

PMID- 11335087
TI  - Immunohistochemical detection of vascular endothelial growth factor (VEGF) and
      VEGF receptors Flt-1 and KDR/Flk-1 in the cochlea of guinea pigs.
AB  - Vascular endothelial growth factor (VEGF) is known as an endothelial cell
      specific mitogen. There are no reports concerning the presence of VEGF in the
      inner ear. To gain information, immunohistochemical analysis using specific
      antibodies to VEGF and to both known VEGF receptors Flt-1 and KDR/Flk-1 was
      performed on paraffin-sectioned temporal bones from five guinea pigs.
      Immunoreactivity of VEGF, Flt-1 and KDR/Flk-1 was detectable in spiral ganglion
      cells. VEGF could also be found in the endothelium of blood vessels, in the
      spiral ligament and in the organ of Corti. Flt-1 was found in the limbus
      epithelium, in all supporting cells of the organ of Corti, in Claudius cells,
      cells of the sulcus and in the spiral ligament. Flk-1 could be detected in some
      supporting cells of the organ of Corti (inner pillar cells and Deiters' cells).
      Immunoreactivity to Flk-1 was also found in endothelium of blood vessels and in
      the spiral ligament. Hair cells showed VEGF immunostaining, but did not contain
      staining to Flt-1 nor Flk-1. In the stria vascularis any immunoreactivity to all
      used VEGF and VEGF receptor antibodies could not be detected. The findings were
      supported by Western blot analysis on inner ear tissues and ovaries from guinea
      pigs. We may conclude that the growth factor VEGF and both receptors participate
      in cochlear physiology.

PMID- 11335090
TI  - MR imaging of pancreatic diseases.
AB  - This article presents current MR imaging techniques for the pancreas, and review
      a spectrum of MR imaging features of various pancreatic diseases. These include:
      1) congenital anomalies such as anomalous union of pancreatobiliary ducts,
      divisum, and annular pancreas, 2) inflammatory diseases, including acute or
      chronic pancreatitis with complications, groove pancreatitis, and autoimmune
      pancreatitis, tumor-forming pancreatitis, 3) pancreatic neoplasms, including
      adenocarcinoma, islet cell tumors, and cystic neoplasms (microcystic adenoma,
      mucinous cystic neoplasms, and intraductal mucin-producing pancreatic tumor).
      Particular attention is paid to technical advances in MR imaging of the pancreas
      such as fat-suppression, MR pancreatography (single- or multi-slice HASTE), and
      thin-section 3D multiphasic contrast-enhanced dynamic sequences. Imaging
      characteristics that may lead to a specific diagnosis or narrow the differential
      diagnosis are also discussed.

PMID- 11335091
TI  - Pancreas: imaging diagnosis with color/power Doppler ultrasonography, endoscopic
      ultrasonography, and intraductal ultrasonography.
AB  - Recent advances of ultrasound imaging have made possible to depict various
      diseases and conditions of the pancreas. Color/power Doppler ultrasonography,
      endoscopic ultrasonography, and intraductal ultrasonography are feasible to show
      vascular abnormalities, differentiate the solid and cystic tumors, decide tumor
      extent, and help to perform interventional treatments of the pancreatic diseases.
      Those techniques will contribute to the more precise and easier diagnosis and to
      prompt decision of the treatments of the pancreatic disorders. Radiologists
      should recognize the diagnostic feasibility and limitations of those techniques
      in order to avoid unnecessary examinations on the patients, and obtain precise
      diagnostic images.

PMID- 11335092
TI  - Radiologic diagnosis and staging of pancreatic ductal adenocarcinoma.
AB  - This article presents imaging modalities in the diagnosis and staging of
      pancreatic ductal adenocarcinoma. Magnetic resonance imaging (MRI) and endoscopic
      ultrasonography (EUS) have the highest accuracy in detection of pancreatic
      cancer. MRI and EUS have similar accuracy in determining the local extent of
      pancreatic cancer. Angiography, computed tomography (CT) angiography and EUS are
      similarly accurate in evaluating peripancreatic vascular involvement. MRI is the
      superior method for detecting liver metastases and peritoneal implants of
      pancreatic ductal adenocarcinoma. Endoscopic retrograde cholangiopancreatography
      (ERCP) and magnetic resonance cholangiopancreatography (MRCP) are used to assess
      the biliary tract of patients with pancreatic cancer. Positron emission
      tomography (PET) is useful in distinguishing pancreatic cancer from focal
      pancreatic inflammation.

PMID- 11335093
TI  - Radiologic features of cystic, endocrine and other pancreatic neoplasms.
AB  - This article presents imaging features of cystic, endocrine and other pancreatic
      neoplasms. Microcystic adenoma which is composed of small cysts (<2 cm), its
      macrocystic subgroup contains solitary cyst. Multiple cysts larger than 2 cm are
      associated with mucinous cystic neoplasm. Swiss cheese appearence with central
      calcification is characteristic for microcystic adenomas. Septal and mural
      enhancement as well as larger size (>2 cm) are accounted for mucinous cystic
      neoplasms, its variant along pancreatic duct is ductectatic mucinous cystic
      neolasm. Endocrine tumors of pancreas are hypervascular and can be depicted on
      early dynamic enhanced crosssectional imaging modalities or on angiography when
      they are <1 cm. Pancreatic metastases and lymphomas are rare neoplasms which
      should also be included in differential diagnosis for pancreatic masses.

PMID- 11335094
TI  - The role of diagnostic radiology in pancreatitis.
AB  - Acute pancreatitis is a frequent inflammatory and necrotic process of pancreas
      and peripancreatic field. To detect the presence of infected or sterile necrotic
      components and hemorrhage of the pancreatic paranchyma is important for
      therapeutic approach. Chronic pancreatitis is characterized by irreversible
      exocrine dysfunction, progressive loss of pancreatic tissue and morphological
      changes of the pancreatic canal. Imaging modalities play a primary role in the
      management of both acute and cronic pancreatitis. CT and MR imaging confirm the
      diagnosis and detect the severity of disease. In chronic pancreatitis, MRCP after
      Secretin administration, Spiral CT and endoscopic US seems to replace diagnostic
      ERCP. However differentiation of pseudotumor of chronic pancreatitis from the
      pancreatic carcinoma is difficult with either imaging modalities.

PMID- 11335095
TI  - Interventional radiology in inflammatory pancreatic disease.
AB  - This article presents a review of the interventional radiological procedures in
      inflammatory pancreatic diseases including imaging guided biopsy, percutaneous
      aspiration and drainage, and transcatheter embolization of ruptured
      pseudoaneurysms.

PMID- 11335096
TI  - Pancreatic carcinoma and fast MR imaging: technical considerations for signal
      intensity difference measurements.
AB  - The aim of the study was to find the fast magnetic resonance imaging (MRI)
      sequence with the best conspicuity of pancreatic lesions at 1.0 T and 1.5 T. A
      total of 51 patients were studied. At 1.0 T, 22 patients with verified malignant
      pancreatic lesions were studied using the T1-weighted breath-hold spoiled
      Gradient Echo 2D FLASH(75) or FLASH(80) sequences, both non-enhanced and enhanced
      with gadolinium. The relative signal intensity difference (SIDR) between lesion
      and pancreas was measured. At 1.5 T, 20 patients with primary malignant lesions
      of the pancreas, and nine patients with 13 benign cystic lesions were examined
      with the breath-hold T2-weighted TrueFISP, HASTE, T1-weighted 2D FLASH(80) and
      FLASH(50) fat saturation sequences, the latter also enhanced. The signal
      intensity (SI) values of the pancreas and lesions as well as the pancreatic
      standard deviation (S.D.) were assessed, and the contrast-to-noise ratio (C/N)
      was determined. Statistical significances were calculated using an analysis of
      variance. No statistically significant difference between the sequences used in
      the conspicuity of cancer was found, either at 1.0 T or at 1.5 T. At 1.5 T, the
      T2-weighted TrueFISP and HASTE sequences could differentiate benign, cystic
      lesions from malignant lesions.

PMID- 11335097
TI  - Pancreatic adenocarcinoma: detection and staging with dynamic MR imaging.
AB  - OBJECTIVE: To compare the efficacy of dynamic contrast-enhanced MR imaging and
      spin-echo T1-weighted with and without fat-saturated MR imaging in the detection
      and staging of pancreatic adenocarcinoma. METHODS AND MATERIAL: Spin-echo T1
      weighted, fat-saturated T1-weighted and dynamic breath-hold 2D-FLASH MR imaging
      were performed in 25 patients with pancreatic adenocarcinoma. MR images were
      analysed by calculating the CNR between tumor and normal portion of the pancreas.
      The CNRs calculated at each sequences were compared. A total of 16 out of 25
      patients underwent surgery. Preoperative staging according to TNM classification
      was also done in patients undergoing surgery. RESULTS: The CNR was significantly
      different (P<0.05) in the arterial phase of dynamic MR images. The accuracy of
      'T' staging was 75% for SE T1-W, fat-saturated T1-W and arterial phase of dynamic
      MR images. CONCLUSION: The CNRs between pancreatic carcinoma and normal pancreas
      is significantly higher in dynamic MR sequences than the SE T1-W, fat-saturated
      T1-W sequences. However, the accuracy of tumor staging according to TNM is
      equivocal to SE T1-W and fat-saturated T1-W images.

PMID- 11335098
TI  - Pancreatic carcinoma: MR, MR angiography and dynamic helical CT in the evaluation
      of vascular invasion.
AB  - OBJECTIVE: To assess the value of MR angiography in combination with contrast
      enhanced MR imaging, and to compare MR imaging including MR angiography with
      dynamic contrast-enhanced dual phase helical CT in the preoperative assessment of
      vascular invasion in patients with suspected pancreatic carcinoma. METHODS AND
      MATERIAL: MR imaging only, MR imaging including MR angiography and dynamic
      contrast-enhanced dual phase helical CT images of 48 patients who were operated
      due to suspicion of pancreas cancer were correlated with the surgery results in
      terms of vascular invasion. Pathologic diagnosis were pancreatic adenocarcinoma
      in 31 patients of which nine had surgically confirmed vascular invasion.
      Sensitivity, specificity, predictive values (including 95% confidence intervals)
      and accuracy of MR imaging only, MR imaging including MR angiography and helical
      CT were calculated. RESULTS: Sensitivity, specificity, positive and negative
      predictive values and accuracy were 56, 100, 100, 85, 87%; 67, 100, 100, 88, 90%
      and 67, 100, 100, 88, 90%, respectively, for MR imaging only, MR imaging
      including MR angiography and helical CT in the adenocarcinoma group. The
      corresponding figures in the overall study group were 56, 97, 83, 90, 90%; 67,
      97, 86, 93, 92% and 67, 97, 86, 93, 92%. Confidence intervals (95%) showed that
      the differences in the diagnostic efficacy of the techniques were not
      statistically significant in the overall study group, but the confidence
      intervals were undefined in the adenocarcinoma group due to the small sample
      size. CONCLUSION: Diagnostic efficacy of MR imaging when combined with MR
      angiography is equal to that of dynamic contrast-enhanced dual phase helical CT
      in the assessment of vascular invasion of pancreatic tumors.

PMID- 11335100
TI  - Androgen induced cell death in SHSY5Y neuroblastoma cells expressing wild-type
      and spinal bulbar muscular atrophy mutant androgen receptors.
AB  - Spinal bulbar muscular atrophy (SBMA) is one of a family of inherited
      neurodegenerative diseases caused by expansion of CAG encoding polyglutamine
      repeats; in SBMA the affected gene is the androgen receptor. To understand
      further the mechanisms that lead to neuronal cell death in SBMA, we generated
      SHSY5Y neuroblastoma cell lines that stably express identical levels of wild-type
      (19 polyglutamine repeat) or SBMA (52 polyglutamine repeat) androgen receptor.
      Parental SHSY5Y cells do not express detectable levels of the androgen receptor.
      In the absence of androgen, the transfected cell lines have similar phenotypes
      and growth characteristics to parental SHSY5Y cells. However, upon treatment with
      androgen, both cell lines undergo a marked dose-dependent loss of viability; this
      loss was significantly greater in cells expressing the SBMA receptor.
      Morphological analyses of the androgen treated cells revealed that cell death
      bore hallmarks of apoptosis involving altered nuclear morphology and cleavage of
      poly(ADP-ribose) polymerase and of caspase 3 in both wild-type and SBMA cell
      lines. The caspase inhibitor VAD-fmk was able to decrease loss of viability of
      both cell lines on exposure to androgen.

PMID- 11335099
TI  - Enhanced expression of mRNAs of antisecretory factor-1, gp96, DAD1 and CDC34 in
      human hepatocellular carcinomas.
AB  - To identify differentially expressed genes in hepatocarcinogenesis, we performed
      differential display analysis using surgically resected hepatocellular carcinoma
      (HCC) and adjacent non-tumorous liver tissues. We identified four cDNA fragments
      upregulated in HCC samples, encoding antisecretory factor-1 (AF), gp96, DAD1 and
      CDC34. Northern blot analysis demonstrated that these mRNAs were expressed
      preferentially in HCCs compared with adjacent non-tumorous liver tissues or
      normal liver tissues from non-HCC patients. The expression of these mRNAs was
      increased along with the histological grading of HCC tissues. These mRNA levels
      were also high in three human HCC cell lines (HuH-7, HepG2 and HLF), irrespective
      of the growth state. We also demonstrate that sodium butyrate, an inducer of
      differentiation, downregulated the expression of AF and gp96 mRNAs, supporting in
      part our pathological observation. Immunohistochemical analysis revealed that
      gp96 and CDC34 proteins were preferentially accumulated in cytoplasm and nuclei
      of HCC cells, respectively. Overexpression of these genes could be an important
      manifestation of HCC phenotypes and should provide clues to understand the
      molecular basis of hepatocellular carcinogenesis.

PMID- 11335101
TI  - Xanthine oxidase-derived reactive oxygen metabolites contribute to liver
      necrosis: protection by 4-hydroxypyrazolo[3,4-d]pyrimidine.
AB  - Xanthine oxidase (XO) generates reactive oxygen metabolites (ROM) as a by-product
      while catalyzing their reaction. The present study implicates these ROM in the
      pathogenesis of liver necrosis produced in rats by the intraperitoneal
      administration of thioacetamide (TAA; 400 mg/kg b.wt.). After 16 h of TAA
      administration, the activity of rat liver XO increased significantly compared to
      that of the control group. At the same time, the level of serum marker enzymes of
      liver necrosis (aminotransferases and alkaline phosphatase) and tissue
      malondialdehyde content also increased in TAA treated rats. Tissue
      malondialdehyde concentration is an indicator of lipid peroxidation and acts as a
      useful marker of oxidative damage. Pretreatment of rats with XO inhibitor (4
      hydroxypyrazolo[3,4-d]pyrimidine; allopurinol (AP)) followed by TAA could lower
      the hepatotoxin-mediated rise in malondialdehyde level as well as the level of
      marker enzymes associated with liver necrosis. The survival rate also increased
      in rats given AP followed by the lethal dose of TAA. In either case, the effect
      of AP was dose-dependent. Results presented in the paper indicate that increased
      production of XO-derived ROM contributes to liver necrosis, which can be
      protected by AP.

PMID- 11335102
TI  - Nuclear cathepsin B-like protease cleaves transcription factor YY1 in
      differentiated cells.
AB  - Differentiation of pluripotent cells into differentiated cell types involves
      changes in many aspects of cellular biochemistry. Many of these changes result in
      alterations of gene expression, which may occur by changing the activity of
      transcription factors. The cell line NTERA-2 (NT2) can be differentiated into
      various cell types by incubation with retinoic acid. The differentiated cell type
      is also permissive for infection with the human herpesvirus cytomegalovirus
      (CMV). The transcription factor YY1 has been shown to regulate the immediate
      early promoter of CMV in a differentiation specific manner by binding to one site
      at -958 to -950 and to at least two sites in the enhancer. It is demonstrated
      here that there is a second YY1 site in the modulator between -995 and -987.
      Levels of YY1 DNA binding activity and protein decrease in NT2 cells as they are
      differentiated with retinoic acid. This decrease in protein is due to the
      degradation of YY1 by a cathepsin B-like activity found in nuclear extracts. The
      cleavage products of YY1 include the intact C-terminal half of the protein, which
      contains the zinc fingers and the DNA binding activity. This suggests a mechanism
      that allows expression of the CMV immediate-early promoter in differentiated
      cells.

PMID- 11335103
TI  - Iron and gallium increase iron uptake from transferrin by human melanoma cells:
      further examination of the ferric ammonium citrate-activated iron uptake process.
AB  - Previously we showed that preincubation of cells with ferric ammonium citrate
      (FAC) resulted in a marked increase in Fe uptake from both (59)Fe-transferrin
      (Tf) and (59)Fe-citrate (D.R. Richardson, E. Baker, J. Biol. Chem. 267 (1992)
      13972-13979; D.R. Richardson, P. Ponka, Biochim. Biophys. Acta 1269 (1995) 105
      114). This Fe uptake process was independent of the transferrin receptor and
      appeared to be activated by free radicals generated via the iron-catalysed Haber
      Weiss reaction. To further understand this process, the present investigation was
      performed. In these experiments, cells were preincubated for 3 h at 37 degrees C
      with FAC or metal ion solutions and then labelled for 3 h at 37 degrees C with
      (59)Fe-Tf. Exposure of cells to FAC resulted in Fe uptake from (59)Fe-citrate
      that became saturated at an Fe concentration of 2.5 microM, while FAC-activated
      Fe uptake from Tf was not saturable up to 25 microM. In addition, the extent of
      FAC-activated Fe uptake from citrate was far greater than that from Tf. These
      results suggest a mechanism where FAC-activated Fe uptake from citrate may result
      from direct interaction with the transporter, while Fe uptake from Tf appears
      indirect and less efficient. Preincubation of cells with FAC at 4 degrees C
      instead of 37 degrees C prevented its effect at stimulating (59)Fe uptake from
      (59)Fe-Tf, suggesting that an active process was involved. Previous studies by
      others have shown that FAC can increase ferrireductase activity that may enhance
      (59)Fe uptake from (59)Fe-Tf. However, there was no difference in the ability of
      FAC-treated cells compared to controls to reduce ferricyanide to ferrocyanide,
      suggesting no change in oxidoreductase activity. To examine if activation of this
      Fe uptake mechanism could occur by incubation with a range of metal ions, cells
      were preincubated with either FAC, ferric chloride, ferrous sulphate, ferrous
      ammonium sulphate, gallium nitrate, copper chloride, zinc chloride, or cobalt
      chloride. Stimulation of (59)Fe uptake from Tf was shown (in order of potency)
      with ferric chloride, ferrous sulphate, ferrous ammonium sulphate, and gallium
      nitrate. The other metal ions examined decreased (59)Fe uptake from Tf. The fact
      that redox-active Cu(II) ion did not stimulate Fe uptake while redox-inactive
      Ga(III) did, suggests a mechanism of transporter activation not solely dependent
      on free radical generation. Indeed, the activation of Fe uptake appears dependent
      on the presence of the Fe atom itself or a metal ion with atomic similarities to
      Fe (e.g. Ga).

PMID- 11335104
TI  - Effect of fluvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A
      reductase, on nitric oxide-induced hydroxyl radical generation in the rat heart.
AB  - We examined the effect of fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A
      (HMG-CoA) reductase inhibitor, on the production of hydroxyl radical (*OH)
      generation via nitric oxide synthase (NOS) activation by an in vivo microdialysis
      technique. The microdialysis probe was implanted in the left ventricular
      myocardium of anesthetized rats and tissue was perfused with Ringer's solution
      through the microdialysis probe at a rate of 1 microl/min. Sodium salicylate in
      Ringer's solution (0.5 nmol/microl/min) was infused directly through a
      microdialysis probe to detect the generation of *OH. Induction of [K(+)](o) (70
      mM) or tyramine (1 mM), significantly increased the formation of *OH trapped as
      2,3-dihydroxybenzoic acid (DHBA). The application of N(G)-nitro-L-arginine methyl
      ester (L-NAME), a NOS inhibitor, significantly decreased the K(+) depolarization
      induced *OH formation, but the effect of tyramine significantly increased the
      level of 2,3-DHBA. When fluvastatin (100 microM), an inhibitor of low-density
      lipoprotein (LDL) oxidation, was administered to L-NAME-pretreated animals, both
      KCl and tyramine failed to increase the level of 2,3-DHBA formation. The effect
      of fluvastatin may be unrelated to K(+) depolarization-induced *OH generation. To
      examine the effect of fluvastatin on ischemic/reperfused rat myocardium, the
      heart was subjected to myocardial ischemia for 15 min by occlusion of the left
      anterior descending coronary artery (LAD). When the heart was reperfused, a
      marked elevation of the level of 2,3-DHBA was observed. However, in the presence
      of fluvastatin (100 microM), the elevation of 2,3-DHBA was not observed in
      ischemia/reperfused rat heart. Fluvastatin, orally at a dose of 3 mg/kg/day for 4
      weeks, significantly blunted the rise of serum creatine phosphokinase and
      improved the electrocardiogram 2 h after coronary occlusion. These results
      suggest that fluvastatin is associated with a cardioprotective effect due to the
      suppression of noradrenaline-induced *OH generation by inhibiting LDL oxidation
      in the heart.

PMID- 11335105
TI  - Glycation decreases calmodulin binding to lens transmembrane protein, MIP.
AB  - Channels of the major intrinsic protein (MIP) of the lens transport water, thus
      playing an important role in lens fiber cell homeostasis. Calmodulin (CAM)
      interacts with MIP and possibly regulates MIP channel permeability. Protein
      glycation has been implicated in lens opacification. We previously identified
      sites of glycation of MIP, which are in close proximity to the putative CAM
      binding site. This study is aimed to show the effect of in vitro and in vivo
      glycation on CAM binding to MIP. Our results show that MIP and MP20 are the major
      CAM binding proteins of the lens membrane. In vitro incubation of lens membranes
      with 1 M glucose decreased CAM binding by 38% (P<0.001). Similarly, there was a
      progressive decrease in CAM binding to diabetic lens membranes compared to age
      matched controls (up to 30% decrease, P<0.01). Mutation of K228 and K238 as well
      as a triple K mutation (K228N, K238N, K259N) of MIP resulted in a decrease in CAM
      binding. Thus, post-translational protein modifications of MIP influence CAM
      binding. Since CAM is the ubiquitous Ca(2+) receptor, decreases in CAM binding to
      the target protein will affect the Ca(2+)-mediated cellular processes leading to
      lens opacification in diabetic and aging lenses.

PMID- 11335106
TI  - Possible participation of a JAK2 signaling pathway in recombinant rat interleukin
      5-induced prolongation of rat eosinophil survival.
AB  - Recombinant rat interleukin (IL)-5-induced prolongation of rat eosinophil
      survival in culture was inhibited in a concentration-dependent manner by the
      protein synthesis inhibitor cycloheximide, the DNA-dependent RNA synthesis
      inhibitor actinomycin D, and the tyrosine kinase inhibitor herbimycin A when
      examined 96 h after incubation. The MEK-1 inhibitor PD98059 inhibited IL-5
      induced phosphorylation of both p44 and p42 MAP kinases, but the IL-5-induced
      prolongation of eosinophil survival was not inhibited. In contrast, the JAK2
      inhibitor AG490 inhibited the IL-5-induced prolongation of eosinophil survival.
      Treatment of eosinophils with IL-5 resulted in phosphorylation of STAT5 but not
      STAT1, and the IL-5-induced phosphorylation of STAT5 was inhibited by AG490.
      These findings suggest that the activation of JAK2 tyrosine kinase and protein
      synthesis are required for the prolongation of rat eosinophil survival induced by
      recombinant rat IL-5. STAT5 phosphorylation might also participate in the IL-5
      induced survival of rat eosinophils.

PMID- 11335107
TI  - The Drosophila castor gene is involved in postembryonic brain development.
AB  - castor (cas) encodes a zink finger protein expressed in a subset of Drosophila
      embryonic neuroglioblasts where it controls neuronal differentiation. We show
      here that cas is expressed at larval and pupal stages in brain cell clusters
      where it participates in the elaboration of the adult structures. In particular
      using the MARCM system (mosaic analysis with a repressible cell marker), we show
      that cas is required postembryonically for correct axon pathfinding of the
      central complex (CX) and mushroom body (MB) neurons. The linotte (lio) gene
      encodes a transmembrane protein expressed at larval/pupal stage in a glial
      structure, the TIFR, and interacts with the no-bridge (nob) gene. We show that
      cas interacts genetically with lio and nob. These interactions do not involve
      direct transcription regulation but probably cellular communication processes.

PMID- 11335108
TI  - cis-acting DNA regulatory elements, including the retinoic acid response element,
      are required for tissue specific laminin B1 promoter/lacZ expression in
      transgenic mice.
AB  - The LAMB1 gene encodes the laminin beta1 subunit of laminin, an extracellular
      matrix protein. Using several transgenic mouse lines containing various lengths
      of the LAMB1 promoter driving lacZ reporter gene expression, regions of LAMB1
      promoter that contain cis-acting DNA regulatory element(s) have been identified.
      The 3.9LAMB1betagal transgene is expressed in various tissues during development.
      LAMB1 transgene expression is observed in a selective set of nephrons of the
      neonatal and adult kidneys. The cis-acting DNA regulatory elements responsible
      for LAMB1 transgene expression in ovaries and in juvenile kidneys are present
      between -'1.4 and -0.7 kb relative to the transcription start site, while those
      of adult kidneys are located between -2.5 and -1.4 kb. The LAMB1 transgene is
      also expressed in the epididymis of 1 week old transgenic mice. Mutation of the
      retinoic acid response element (RARE) in the context of the 3.9LAMB1betagal
      transgene results in loss of LAMB1 transgene expression in all tissues. Thus,
      sequences between -2.5 and -0.7 kb plus the RARE are required for appropriate
      expression of the LAMB1 transgene in mice.

PMID- 11335109
TI  - Wnt-3a is required for somite specification along the anteroposterior axis of the
      mouse embryo and for regulation of cdx-1 expression.
AB  - In vertebrates, each vertebra along the anteroposterior axis has a characteristic
      structure. It has recently been shown that several transcription factors and cell
      signaling molecules expressed in the primitive streak ectoderm and/or the tailbud
      play essential roles in establishing the correct anteroposterior specification of
      vertebrae during mouse development. Here, we report that Wnt-3a mutants exhibit
      homeotic transformations in the vertebrae along their entire body axis. In
      addition, reduced expression of cdx-1, the mutation of which results in an
      anterior transformation, as occurs in Wnt-3a mutants, was observed in the
      primitive streak and tail bud region of Wnt-3a mutant embryos. These results
      indicate that Wnt-3a is necessary for correct anteroposterior patterning of
      vertebra, and that cdx-1 may be one of the mediator genes of Wnt-3a signaling in
      this process.

PMID- 11335110
TI  - Epigenetic targeting in the mouse zygote marks DNA for later methylation: a
      mechanism for maternal effects in development.
AB  - The transgenic sequences in the mouse line TKZ751 are demethylated on a DBA/2
      inbred strain background but become highly methylated at postimplantation stages
      in offspring of a cross with a BALB/c female. In the reciprocal cross the
      transgene remains demethylated suggesting that imprinted BALB/c methylation
      modifiers or egg cytoplasmic factors are responsible for this striking maternal
      effect on de novo methylation. Reciprocal pronuclear transplantation experiments
      were carried out to distinguish between these mechanisms. The results indicate
      that a maternally-derived oocyte cytoplasmic factor from BALB/c marks the TKZ751
      sequences at fertilization; this mark and postzygotic BALB/c modifiers are both
      required for de novo methylation of the target sequences at postimplantation
      stages. Using genetic linkage analyses we mapped the maternal effect to a locus
      on chromosome 17. Moreover, seven postzygotic modifier loci were identified that
      increase the postimplantation level of methylation. Analysis of interactions
      between the maternal and the postzygotic loci shows that both are needed for de
      novo methylation in the offspring. The combined experiments thus reveal a novel
      epigenetic marking process at fertilization which targets DNA for later
      methylation in the foetus. The most significant consequence is that the genotype
      of the mother can influence the epigenotype of the offspring by this marking
      process. A number of parental and imprinting effects may be explained by this
      epigenetic marking.

PMID- 11335111
TI  - Characterisation of Wnt gene expression during the differentiation of murine
      embryonic stem cells in vitro: role of Wnt3 in enhancing haematopoietic
      differentiation.
AB  - The first haematopoietic stem cells in mammalian and non-mammalian vertebrates
      are derived from mesoderm, therefore genes that are important in mesoderm
      patterning and formation might also play an essential role in haematopoietic stem
      cell commitment and differentiation. Several members of the Wnt gene family are
      expressed in very specific patterns in embryonic mesoderm and have previously
      been shown to act as haematopoietic growth factors. In order to investigate in
      detail the role that such secreted proteins play in the biology of early
      haematopoietic commitment we have used in vitro differentiation of murine
      embryonal stem (ES) as a model system. Using reverse-transcriptase polymerase
      chain reaction analysis we identified several candidate Wnt genes whose
      expression pattern was consistent with a role in generation, maintenance and/or
      differentiation of early haematopoietic progenitor cells including three genes
      previously shown to have a role in haematopoiesis (Wnt5a, Wnt2b and Wnt10b). The
      most interesting candidate was Wnt3, because of its strong and regulated
      expression during in vitro differentiation of murine ES cells as well as its
      early embryonic expression in mesoderm. Overexpression of Wnt3 was sufficient to
      cause a consistent increase in the number of embryoid bodies committing to
      haematopoiesis further strengthening the evidence that this protein can enhance
      haematopoietic commitment during in vitro differentiation of ES cells. In
      addition, overexpression of Wnt3 caused a marked upregulation of Brachyury
      expression, thus providing some evidence that Brachyury may be one of the target
      genes for the Wnt3 signalling pathway.

PMID- 11335112
TI  - Misexpression of Xsiah-2 induces a small eye phenotype in Xenopus.
AB  - Recent data demonstrate a structural and functional conservation of factors
      crucial for the development of the insect and the vertebrate eye. We isolated
      Xenopus siah-2, a protein with 67% identity to Drosophila sina (seven in
      absentia) and 85% identity to the mouse and human siah-2 proteins. Sina is
      required in Drosophila for the R7 photoreceptor cell formation during eye
      development, because it down regulates proteins that inhibit R7 differentiation
      via the ubiquitin/proteasome pathway. Nothing is known about the developmental
      function of the siah protein in vertebrates. We show that in Xenopus siah-2 is
      expressed maternally and is later restricted to the brain, spinal cord and the
      developing and mature eye. To demonstrate that the vertebrate factor participates
      in the process of eye formation we over expressed Xsiah-2 during Xenopus
      development and observed the formation of a small eye phenotype. The vertebrate
      counterpart of a C-terminal loss of function sina mutant, that causes a
      deficiency of the R7 photoreceptor cells in Drosophila, induces in Xenopus also
      smaller eyes. The small eyes are characterized by a reduced size of the lens, the
      retina and the pigmented epithelium. As this phenotype has been also described
      for flies expressing sina ectopically, the data demonstrate the functional and
      structural conservation of Xsiah-2 and sina in metazoan eye development.

PMID- 11335113
TI  - Differential expression and function of the Drosophila Pax6 genes eyeless and
      twin of eyeless in embryonic central nervous system development.
AB  - We analyzed the expression and function of eyeless (ey) and twin of eyeless (toy)
      in the embryonic central nervous system (CNS) of Drosophila. Both genes are
      differentially expressed in specific neuronal subsets (but not in glia) in every
      CNS neuromere, and in the brain, specific cell populations co-expressing both
      proteins define a longitudinal domain which is intercalated between broad
      exclusive expression domains of ey and toy. Studies of genetic null alleles and
      dsRNA interference did not reveal any gross neuroanatomical effects of ey, toy,
      or ey/toy elimination in the embryonic CNS. In contrast, targeted misexpression
      of ey, but not of toy, resulted in profound axonal abnormalities in the embryonic
      ventral nerve cord and brain.

PMID- 11335114
TI  - Identification of a new gene family specifically expressed in chicken embryonic
      stem cells and early embryo.
AB  - Chicken embryonic stem (CES) cells are pluripotent cells derived from chicken
      early blastoderm. In order to identify new genes specifically expressed in these
      pluripotent cells, we have used a gene trap strategy and cloned a novel gene
      family called cENS for chicken Embryonic Normal Stem cell gene. The cENS genes
      expression decreases after induction of CES cells differentiation in culture and
      is restricted in vivo to the very early embryo. We have characterized three
      different cENS genes. One, cENS-1, is composed of an open reading frame inserted
      between two terminal direct repeats which are the common point of the cENS genes.
      cENS-1 encodes a protein identical to cERNI, a recently described protein. cENS-2
      is a truncated form of cENS-1. cENS-3 presents two adjacent open reading frames
      coding respectively for env and pol related proteins. The presence of conserved
      direct repeats, of retrovirus related genes and the absence of introns argue in
      favor of a retroviral origin of the cENS genes. In the cENS we identified a
      promoter region whose activity is strong in CES cells and decreases after induced
      differentiation showing a highly specific transcriptional activity specific of
      undifferentiated chicken embryonic stem cells.

PMID- 11335115
TI  - Overexpression of the transcriptional repressor FoxD3 prevents neural crest
      formation in Xenopus embryos.
AB  - Xenopus FoxD3 (XFD-6) is an intron-less gene initially expressed within the
      Spemann organizer and later in premigratory neural crest cells. Based upon
      sequence and expression pattern comparisons, it represents the Xenopus orthologue
      to zebrafish fkd6, chicken CWH-3 and mammalian HFH-2 (genesis). Early expression
      of FoxD3 is activated by the Wnt-pathway and inhibited by BMP signalling. Ectopic
      overexpression of FoxD3 leads to an enlargement of the neural plate concomitant
      with a failure in neural crest formation, loss of anterior structures, lack of
      closure of the neural tube and severe defects in somitogenesis. Phenotypic
      variation is accompanied by down-regulation of neural crest markers, including
      Xslug, Xtwist and Xcadherin-11. FoxD3 also inhibits its own expression, thereby
      acting in a negative autoregulatory loop. By injections of VP16 and engrailed
      fusions we can demonstrate that FoxD3 acts as a negative transcriptional
      regulator; this repressive function strictly requires the presence of the winged
      helix domain. Transplantation experiments show that FoxD3 overexpressing cells
      from the prospective neural crest do neither differentiate nor migrate.

PMID- 11335116
TI  - The orphan nuclear receptor BmHR3A of Bombyx mori: hormonal control, ovarian
      expression and functional properties.
AB  - Ovarian development in the domesticated silkmoth, Bombyx mori, is induced by the
      molting hormone 20-hydroxy-ecdysone (20E) shortly after larval-pupal ecdysis.
      Studies of the ecdysone response in Drosophila and other insects have shown that
      20E exerts its effects initially by the induction of a small number of early
      genes, including the orphan nuclear receptors HR3, that transduce and amplify the
      hormone signal. Here we show that the silkmoth orphan receptor BmHR3A acts in the
      20E-induced regulatory cascade in the ovary during pupal and pharate adult
      development in a manner different than that observed in the classical ecdysone
      regulatory hierarchy in Drosophila salivary glands at the end of the third
      instar. While other isoforms of BmHR3 are induced as early gene products in the
      ecdysone response, BmHR3A is induced 2 days after 20E administration in the
      silkmoth ovary and, thus, behaves as late product. The period of accumulation of
      BmHR3A in ovarian follicular cells occurs during vitellogenesis and coincides
      with the period of transcriptional expression of the ESP (egg-specific protein)
      gene, whose product constitutes a major component of the egg yolk, while it is
      reciprocal to the period of expression of BmGATAbeta, a gene encoding a regulator
      of late chorion gene expression. Bandshift experiments demonstrate that BmHR3A
      binds specifically to RORE (Retinoic acid-related Orphan receptor Response
      Element)-like sequences in the promoters of both genes, thus suggesting a direct
      role for BmHR3A in regulating the expression of BmGATAbeta and ESP genes during
      vitellogenesis. Finally, we show that BmHR3A functions as a constitutive
      transcriptional activator in a B. mori derived cell line. We propose that BmHR3A
      may function as a regulator of vitellogenesis in the silkmoth ovary.

PMID- 11335117
TI  - Expression of DWnt6, DWnt10, and DFz4 during Drosophila development.
AB  - Members of the Wnt gene family encode secreted proteins that signal through the
      Frizzled family of receptors to function in many aspects of development. In this
      study, we have analyzed the expression of two Wnt genes and one Frizzled family
      member that were recently identified through the Drosophila genome sequencing
      project. We show that DWnt6 is only weakly expressed in developing embryos, with
      transcripts faintly detected in the gut. By late third instar however, this gene
      is expressed in a pattern that is identical to that of wingless (wg) in the
      imaginal discs. DWnt10 is expressed in the embryonic mesoderm, central nervous
      system and gut, whereas its expression is below the levels of our detection in
      third instar imaginal discs. We find that DFz4 is also expressed in a dynamic
      pattern in the mesoderm, gut, and central nervous system.

PMID- 11335118
TI  - Developmental expression of myotilin, a gene mutated in limb-girdle muscular
      dystrophy type 1A.
AB  - We analyzed developmental expression of myotilin, a novel sarcomeric component
      mutated in limb-girdle muscular dystrophy 1A (LGMD1A). In situ hybridization and
      immunostaining of embryonic mouse tissues revealed expression of myotilin
      initially (E9-10) in heart, somites and neuroepithelium. At E13 myotilin was
      expressed in a variety of tissues, including the nervous system, lung, liver and
      kidney, but upon organ differentiation expression became more restricted. The
      level of expression during early development is comparable between mouse and
      human, indicating that the mouse may provide a model for further studying the
      functions of myotilin and the pathogenesis of LGMD1A.

PMID- 11335119
TI  - Pbx4, a new Pbx family member on mouse chromosome 8, is expressed during
      spermatogenesis.
AB  - Members of the Pbx family are involved in a diverse range of developmental
      processes including axial patterning and organogenesis. Pbx functions are in part
      mediated by the interaction of Pbx proteins with members of the Hox and Meis/Prep
      families. We have identified a fourth mammalian Pbx family member. Pbx4 in the
      mouse and PBX4 in humans are located on chromosome 8 and chromosome 19,
      respectively. Pbx4 expression is confined to the testis, especially to
      spermatocytes in the pachytene stage of the first meiotic prophase.

PMID- 11335120
TI  - Xenopus frizzled-5: a frizzled family member expressed exclusively in the neural
      retina of the developing eye.
AB  - We have isolated a new Wnt receptor frizzled family member from Xenopus laevis,
      Xenopus frizzled-5 (Xfz5), a likely ortholog of human frizzled-5. Based on
      Northern and whole-mount in situ hybridization data, Xfz5 is first detected at
      the late neurula stage in retinal primordia. Throughout the tailbud stage Xfz5 is
      expressed exclusively in the neural retina within the optic vesicles. During
      tadpole stage Xfz5 expression becomes restricted to the ciliary marginal zone.
      This highly restrictive expression pattern makes Xfz5 an excellent marker for
      neural retinal tissue.

PMID- 11335121
TI  - Developmental analysis of ceruloplasmin gene and liver formation in zebrafish.
AB  - Formation of the liver in zebrafish has been analyzed during normal embryogenesis
      using ceruloplasmin (Cp) as a specific marker. The asymmetric expression of Cp
      has been detected in dorsal endoderm at 16 hpf and later in the early hepatic
      cells in the yolk sac. The liver primordium can be detected after 32 hpf. In oep
      /- mutant, which lacks dorsal endoderm, the liver fails to form. In the
      notochordless flh-/- mutant, the asymmetry of the liver has been lost. Therefore
      the notochord, dorsal endoderm and endoderm of the yolk sac play a role in liver
      formation in zebrafish.

PMID- 11335122
TI  - Gcm2 and Foxn1 mark early parathyroid- and thymus-specific domains in the
      developing third pharyngeal pouch.
AB  - The thymus and parathyroids originate from a common primordium that develops from
      the third pharyngeal pouch in mice and humans. The molecular mechanism that
      specifies this primordium into distinct organ domains is not known. The Gcm2 and
      Foxn1 transcription factors are required for development of the parathyroid and
      thymus respectively, and are attractive candidates for this role. However, their
      embryonic expression patterns during pharyngeal pouch development and early
      thymus and parathyroid organogenesis have not been described. Here we report that
      Gcm2 is expressed specifically in the developing second and third pharyngeal
      pouches at E9.5, and is further confined to a small domain of the third pouch
      endoderm by E10.5. In contrast, Foxn1 is not expressed until after the common
      primordium is formed, beginning at E11.25. Our results show that Gcm2 and Foxn1
      expression mark two complementary domains that prefigure parathyroid and thymus
      regions within the common primordium before morphological distinctions are
      present.

PMID- 11335123
TI  - Developmental expression patterns of the signaling adapters FRS-2 and FRS-3
      during early embryogenesis.
AB  - Two fibroblast growth factor (FGF) receptor substrates (FRS2 and FRS3) are
      involved in downstream signaling from activated FGF receptors and neurotrophin
      activated Trk receptors. Despite the importance of signaling from these factors
      in embryogenesis, FRS2 and FRS3 expression patterns during development are
      unknown. In this study we characterize the expression of FRS2 and FRS3 from E7 to
      parturition and in adult murine tissues. Both are first detected in whole E8.5
      CD1 mouse embryos. FRS2 is detected as early as E7 in the developing
      syncytiotrophoblast, later in the neural tube (NT) and in many adult and fetal
      tissues. FRS3 is more restricted in location than FRS2 (fetal NT, heart, stomach,
      liver and some adult tissues), and is expressed predominantly in the ventricular
      layer of the developing NT and brains of murine embryos.

PMID- 11335124
TI  - Expression of Klf9 and Klf13 in mouse development.
AB  - Klf9 and Klf13 are members of the C(2)H(2) zinc finger family of transcription
      factors that are thought to be involved in regulating basal transcription. The
      mRNA localization of Klf9 and Klf13 during development was determined by in situ
      hybridization of mouse E8, E11, E13 and E16 embryo sections. The data showed that
      Klf9 and Klf13 are widely expressed at all the mouse embryo stages examined.
      Whilst the expression patterns of the two genes largely overlap there are
      differences in the localization or level of expression in some tissues. At E11,
      both genes are expressed in high levels in the cephalic mesenchyme whilst Klf13
      and not Klf9 is expressed at high levels in the developing heart at E8 and E11.
      In the gut and bladder at E16, Klf13 is expressed in the epithelial cell layer
      whereas Klf9 is expressed in both the muscle and epithelial layers. Both Klf9 and
      Klf13 are expressed at high levels in the epidermis at E11, E13 and E16.

PMID- 11335126
TI  - Drosophila regulatory factor X is an embryonic type I sensory neuron marker also
      expressed in spermatids and in the brain of Drosophila.
AB  - We report the expression pattern of a Drosophila transcription factor, Drosophila
      regulatory factor X (dRFX), which belongs to the RFX winged-helix transcription
      factor family. dRFX is distributed in type I sensory neuron lineage of the
      peripheral nervous system throughout Drosophila development and thus represents
      the first described type I lineage characteristic marker in Drosophila. In
      addition, dRFX is also detected in the brain throughout development and in
      spermatids in adult flies.

PMID- 11335125
TI  - Gene expression in the embryonic Xenopus liver.
AB  - In recent years, significant progress has been made in uncovering the molecular
      basis of endoderm specification in Xenopus. Much less is understood, however,
      about endodermal patterning and how endoderm-derived organs such as the liver are
      formed. Progress has been hampered by the lack of good molecular markers of
      presumptive liver tissue. Here, we have examined the embryonic expression of a
      number of marker genes during liver organogenesis, including the transcription
      factors hex, sox17alpha, and hnf3beta, as well as a number of proteins specific
      to the adult liver. Interestingly, sox17alpha appears to specifically mark the
      gall bladder precursors. At 7 days of development expression of the liver
      differentiation markers albumin, alpha1-microglobulin/bikunin precursor,
      fibrinogen, transferrin and transthyretin is restricted to the differentiating
      liver bud. Surprisingly, however, at 3 days of development most of these genes
      have a more widespread endodermal expression pattern. In addition to expression
      in the undifferentiated liver bud they were expressed extensively throughout the
      presumptive intestinal tissue, which may reflect some general feature of how the
      hepatic gene program is developmentally regulated.

PMID- 11335127
TI  - Preferential expression of Mdm2 oncogene during the development of neural crest
      and its derivatives in mouse early embryogenesis.
AB  - The Mdm2 oncoprotein acts as the principal negative regulator of p53 activities
      and is essential for its control during mouse early development, at least before
      implantation. We analyzed Mdm2 expression between 7.5 and 9 days post-coitum
      (dpc) by whole-mount in situ hybridization and report here a novel expression
      pattern during neural crest development. At 7.5 dpc Mdm2 becomes preferentially
      expressed at the top of the neural folds. Between 8 and 9 dpc, this preferential
      expression is also observed in neural crest cells migrating from the closing
      brain towards craniofacial regions and the first three branchial arches. It
      persists in the craniofacial mesenchyme and the first branchial arch in 9 dpc
      embryos. Migrating neural crest cells in the tail region are also preferentially
      labeled at this stage. At day 9.5 Mdm2 becomes more ubiquitously expressed
      throughout the embryo as reported before.

PMID- 11335128
TI  - Wnt receptors and Wnt inhibitors are expressed in gradients in the developing
      telencephalon.
AB  - The caudomedial margin of the medial pallium, known as the cortical hem,
      expresses several Wnt genes that have been shown to be crucial for cortical
      development. We examined the expression of members of the Frizzled (mFz) family
      of Wnt receptors and the Secreted Frizzled Related Protein (SFRP) family of Wnt
      inhibitors during telencephalic development. We found that mFz-5 and mFz-8 are
      specifically expressed in the neocortical neuroepithelium and excluded from the
      hippocampal neuroepithelium in early telencephalic development, whereas mFz-9 and
      mFz-10 have expression domains confined to the medial pallium. In addition, SFRP
      1 and SFRP-3 are expressed in opposing anterolateral to caudomedial gradients
      within the telencephalic ventricular zone throughout corticogenesis.

PMID- 11335129
TI  - Localization of the netrin guidance receptor, DCC, in the developing peripheral
      and enteric nervous systems.
AB  - Over recent years the secreted guidance cue, netrin-1, and its receptor, DCC,
      have been shown to be an essential guidance system driving axon pathfinding
      within the developing vertebrate central nervous system (CNS). Mice lacking DCC
      exhibit severe defects in commissural axon extension towards the floor plate
      demonstrating that the DCC-netrin guidance system is largely responsible for
      directing axonal projections toward the ventral midline in the developing spinal
      cord (Fazeli et al., Nature 386 (1997) 796). In addition, these mutants lack
      several major commissures within the forebrain, including the corpus callosum and
      the hippocampal commissure. In contrast to the CNS, the role of the DCC guidance
      receptor in the development of the mammalian peripheral and enteric nervous
      systems (PNS and ENS) has not been investigated. Here we demonstrate using
      immunohistochemical analysis that the DCC receptor is present in the developing
      mouse PNS where it is found on spinal, segmental, and sciatic nerves, and in
      developing sensory ganglia and their associated axonal projections. In addition,
      DCC is present in the ENS throughout the early developmental phase.

PMID- 11335130
TI  - Tissue-specific expression of the transcriptionally regulated serum and
      glucocorticoid-inducible protein kinase (Sgk) during mouse embryogenesis.
AB  - In situ hybridization of mouse embryo whole mounts and sagittal sections revealed
      a tissue- and stage-specific expression pattern of the transcriptionally
      regulated serum and glucocorticoid-inducible protein kinase (sgk) during
      embryogenesis. Sgk expression is first observed at embryonic day 8.5 (E8.5) in
      the decidua and yolk sac, and then during developmental stages E9.5 through E12.5
      this kinase is highly localized in the heart chamber, otic vesicle, blood vessels
      surrounding the somites, and lung buds. At the later stages of mouse
      embryogenesis, E13.5 through E16.5, sgk expression becomes highly concentrated in
      brain (choroid plexus), distal epithelium and the terminal bronchi/bronchioles,
      adrenal gland, liver, thymus and intestines, remains high in heart tissue, and is
      expressed at a low level in the other embryonic tissues.

PMID- 11335131
TI  - Periostin (an osteoblast-specific factor) is expressed within the embryonic mouse
      heart during valve formation.
AB  - Periostin was originally isolated as a osteoblast-specific factor that functions
      as a cell adhesion molecule for preosteoblasts and is thought to be involved in
      osteoblast recruitment, attachment and spreading. Additionally, periostin
      expression has previously been shown to be significantly increased by both
      transforming growth factor beta-1(TGFbeta1) and bone morphogenetic protein (BMP)
      2. Likewise the endocardial cushions that form within embryonic heart tube
      (embryonic day (E)10-13) are formed by the recruitment, attachment and spreading
      of endocardial cells into the overlying extracellular matrix, in response to
      secreted growth factors of the TGFbeta and BMP families. In order to determine
      whether periostin is similarly involved in heart morphogenesis, in situ
      hybridization and reverse transcription-polymerase chain reaction were used to
      detect periostin mRNA expression in the developing mouse heart. We show for the
      first time that periostin mRNA is expressed in the developing mouse embryonic and
      fetal heart, and that it is localized to the endocardial cushions that ultimately
      divide the primitive heart tube into a four-chambered heart.

PMID- 11335132
TI  - Xenopus Eya1 demarcates all neurogenic placodes as well as migrating hypaxial
      muscle precursors.
AB  - We cloned two isoforms of the Xenopus Eya1 orthologue. They show identical
      patterns of expression that closely resemble the previously described expression
      of XSix1, but partly differ from the expression of Eya1 in other vertebrates.
      XEya1 is expressed in the somites and hypaxial muscle precursors, but not in the
      pronephros. Moreover, all ectodermal placodes except the lens placode strongly
      express XEya1. At neural plate stages, ectodermal XEya1 expression starts in two
      domains, the anterior neural folds and a domain lateral to the neural folds. At
      tailbud stages, XEya1 expression continues in the adenohypophysis, all neurogenic
      placodes and placodally-derived structures including cranial ganglia, the otic
      vesicle and lateral line primordia.

PMID- 11335133
TI  - Expression of Irx6 during mouse morphogenesis.
AB  - Iroquois (Irx) proteins comprise a family of homeodomain-containing transcription
      factors involved in patterning and regionalization of embryonic tissues in both
      vertebrates and invertebrates. The six murine Irx genes are organized in two
      clusters, each consisting of three genes. Irx1, Irx2 and Irx4 belong to the IrxA
      cluster on chromosome 13, whereas Irx3, Irx5 and Irx6, comprising the IrxB
      cluster, are located on chromosome 8 (Peters et al., Genome Res. 10 (2000) 1453).
      Developmental expression patterns have so far only been reported for five Irx
      genes. Here, we investigated the expression pattern of Irx6 during mouse
      morphogenesis and early organogenesis. The pattern was found to be much more
      restricted compared to the other five Irx genes, and its level of expression was
      much lower.

PMID- 11335134
TI  - Protein kinase C isoenzyme: selective expression pattern of protein kinase C
      &theta; during mouse development.
AB  - Protein kinase C (PKC)-&theta;, a serine/threonine protein kinase and novel PKC
      subfamily member, has been recently identified as an essential component of the T
      cell synapse which activates the NF-kB signaling cascade leading to expression of
      the IL-2 gene during T cell activation. By RNA in situ hybridization to whole
      body embryo sections it is shown that the murine PKC&theta; is specifically
      expressed in tissues with hematopoietic and lymphopoietic activity. Expression is
      also evident in skeletal muscle. A further highly specific expression was
      observed in the peripheral and central nervous system which is described in
      detail. Expression in the brain persists up to adult stages.

PMID- 11335135
TI  - Flow cytometric analysis of the localization of Helicobacter pylori antigens
      during different growth phases.
AB  - Previous studies on the localization of several different Helicobacter pylori
      antigens have been contradictory. We have therefore examined by using both one-
      and two-color flow cytometry (FCM), immunofluorescence (IF), and immunoelectron
      microscopy (IEM), the possible surface localization of some H. pylori antigens
      that may be important virulence factors. All four methods detected the
      lipopolysaccharide and the N-acetyl-neuroaminyllactose-binding hemagglutinin
      protein (HpaA) as surface-exposed, while the urease enzyme was not detected at
      all and the neutrophil activating protein only in low concentration on the
      surface of the H. pylori bacteria during culture of H. pylori in liquid broth for
      11 days. The FCM analysis was found to be quite sensitive and specific and also
      extremely fast compared with IF and IEM, and therefore the preferred method for
      detection of surface-localized antigens of H. pylori.

PMID- 11335136
TI  - Cytotoxic factor-autoantibodies: possible role in the pathogenesis of dengue
      haemorrhagic fever.
AB  - During dengue virus infection a unique cytokine, cytotoxic factor (hCF), is
      produced that is pathogenesis-related and plays a key role in the development of
      dengue haemorrhagic fever (DHF). However, what regulates the adverse effects of
      hCF is not known. We have previously shown that anti-hCF antibodies raised in
      mice, neutralise the pathogenic effects of hCF. In this study we have
      investigated the presence and levels of hCF-autoantibodies in sera of patients
      with various severity of dengue illness (n=136) and normal healthy controls
      (n=50). The highest levels of hCF-autoantibodies (mean+/-S.D.=36+/-20 U ml(-1))
      were seen in patients with mild illness, the dengue fever (DF), and 48 out of 50
      (96%) of the sera were positive. On the other hand the hCF-autoantibody levels
      declined sharply with the development of DHF and the levels were lowest in
      patients with DHF grade IV (mean+/-S.D.=5+/-2 U ml(-1); P=<0.001 as compared to
      DF). Only one of the 13 DHF grade IV patients had an antibody level above the
      'cut-off' value (mean plus 3 S.D. of the control sera). The analysis of data with
      respect to different days of illness further showed that the highest levels of
      hCF-autoantibodies were present in DF patients at >9 days of illness. Moreover,
      the DF patients at all time points, i.e. 1-4, 5-8 and >9 days of illness had
      significantly higher levels of hCF-autoantibodies (P<0.001) than patients with
      DHF grade I, II, III and IV. In addition DHF grade I and grade II patients had
      significantly more positive specimens than DHF grade III and grade IV patients at
      all time points. These results suggest that elevated levels of hCF-autoantibodies
      protect the patients against the development of severe forms of DHF and,
      therefore, it may be useful as a prognostic indicator.

PMID- 11335137
TI  - Helicobacter felis does not stimulate human neutrophil oxidative burst in
      contrast to 'Gastrospirillum hominis' and Helicobacter pylori.
AB  - Helicobacter pylori is a human pathogen, whereas the natural hosts for
      'Gastrospirillum hominis' and Helicobacter felis are animals. 'G. hominis' is
      occasionally found to cause infection in humans, whereas H. felis only rarely
      infects humans. The pathogenesis of H. pylori infection is not completely
      understood and in order to reveal differences in immune response to the three
      Helicobacter species, the upregulation of adherence molecule CD11b/CD18,
      chemotactic activity and oxidative burst response of neutrophils after
      stimulation with H. pylori, 'G. hominis' and H. felis sonicates, were compared.
      Like H. pylori, 'G. hominis' and H. felis induced upregulation of CD11b/CD18 and
      chemotaxis of neutrophils. 'G. hominis' demonstrated a more pronounced
      upregulation of CD11b/CD18, whereas H. felis was the strongest stimulant of
      neutrophil chemotaxis. H. felis was unable to stimulate neutrophils to oxidative
      burst response, whereas 'G. hominis' activated neutrophils in a dose-dependent
      way similar to H. pylori. 'G. hominis' and H. felis were both able to prime
      neutrophils for oxidative burst response similar to H. pylori. In conclusion, we
      observed clear differences in neutrophil responses to different Helicobacter
      species, which indicates that bacterial virulence factors may be important for
      the diversity in the pathogenetic outcome of Helicobacter infections.

PMID- 11335138
TI  - Pathogenesis of herpes simplex virus type 2 experimental genital infection in
      pregnant mice.
AB  - The progression of herpes simplex-2 genital infection in pregnant mice was
      studied by detection of viral antigens using immunoperoxidase in tissue sections,
      electron microscopy and virus isolation. The majority of mice (66.66%) died at 8
      9 days post-inoculation. Abortions were observed in 69.23% of the infected mice
      along with impairment of labor and delivery. Herpes antigens were detected in
      most of the autonomic nerves of the uterus, including those surrounding small
      arterioles in the myometrium and the Auerbach and Meissner plexa of the large
      bowel, but not in the abortions or placentas. The infection of uterine autonomic
      fibers and myometrial cells could explain the delivery impairment and could have
      provoked a decrease in blood flow leading to abortions.

PMID- 11335139
TI  - Flagellin expressed by live Salmonella vaccine strains induces distinct antibody
      responses following delivery via systemic or mucosal immunization routes.
AB  - Salmonella flagellin, expressed as flagella in live attenuated vaccine strains,
      elicits distinct systemic (IgG) and secreted (IgA) antibody responses in mice
      following delivery via mucosal (nasal/oral) or parenteral (intraperitoneal
      (i.p.)) immunization routes. Reduced flagellin-specific antibodies were detected
      either systemically or locally following delivery of flagellated derivatives of
      aroA Salmonella enterica serovar Dublin SL1438 via the nasal route, the most
      effective mucosal site for activation of immune responses in mice. In contrast,
      flagellin represents the most potent Salmonella antigen for the generation of
      specific serum antibody (IgG) responses following i.p. inoculations. The distinct
      immunogenic properties of Salmonella flagellin could not be ascribed to deficient
      colonization, reduced invasive ability or loss of the flagellin expression by the
      flagellated vaccine strains.

PMID- 11335140
TI  - Basic streptococcal superantigens (SPEX/SMEZ or SPEC) are responsible for the
      mitogenic activity of the so-called mitogenic factor (MF).
AB  - The mitogenic factor (MF) of group A streptococci has been reported to be a
      superantigen stimulating human T cells carrying Vbeta2, 4 and 8 and has been
      designated streptococcal pyrogenic exotoxin F (SPEF). MF was also shown to
      possess DNase activity. Here we have purified MF from culture supernatants of
      different Streptococcus pyogenes strains. Surprisingly, the MF preparations from
      different strains showed different Vbeta specificities depending on the
      expression of SPEC or SMEZ3 by the producing strain. Their mitogenic activity
      decreased upon further purification. In addition, the mitogenic activity could be
      only neutralized by antibodies against the basic streptococcal superantigens SPEC
      or SPEX (SMEZ3) but not by antibodies against MF itself although the latter were
      able to neutralize completely the DNase activity of MF. We found that
      streptodornase type B (SDB) was expressed in two molecular forms (SDBI and
      SDBII), differing only by one additional N-terminal arginine at SDBI. MF was
      found identical to the enzyme SDBII but is devoid of superantigenic properties
      and should no longer be called a superantigen or a pyrogenic exotoxin.

PMID- 11335141
TI  - Differences in the gut bacterial flora of healthy and milk-hypersensitive adults,
      as measured by fluorescence in situ hybridization.
AB  - We enumerated the predominant gut genera from fecal samples of nine healthy and
      eight milk-hypersensitive adults both before and after 4 weeks Lactobacillus
      rhamnosus GG (LGG) supplementation. The anaerobic intestinal microflora of milk
      hypersensitive adults was found to resemble that of healthy adults. LGG
      consumption resulted in a significant increase in the number of bifidobacteria in
      healthy but not in milk-hypersensitive subjects, as well as a general increase in
      bacterial numbers in all other bacterial genera tested in both groups. In
      conclusion, the composition of the gut microbiota in milk-hypersensitive adults
      appears to be normal. LGG may have potential in reinforcing the endogenous flora.

PMID- 11335142
TI  - Structural and serological studies on Hafnia alvei O-specific polysaccharide of
      alpha-D-mannan type isolated from the lipopolysaccharide of strain PCM 1223.
AB  - On the basis of chemical and methylation analyses, one- and two-dimensional (1)H-
      and (13)C-NMR spectroscopy, including COSY, TOCSY, NOESY and (1)H, (13)C HSQC
      experiments, a neutral O-specific polysaccharide isolated from Hafnia alvei
      strain PCM 1223 lipopolysaccharide (LPS) was found to be an alpha-mannan composed
      of pentasaccharide repeating units having the following structure:-->3)-alpha-D
      Manp-(1-->3)-alpha-D-Manp-(1-->2)-alpha-D-Manp-(1-->2)-alpha-D-Manp-(1-->2)-alpha
      D-Manp-(1-->. Immunoblotting showed a strong cross-reactivity between anti-H.
      alvei PCM 1223 serum and LPSs of Escherichia coli O9 and Klebsiella pneumoniae
      O3. The serological relationship of the LPSs of these bacteria is due to the
      structural identity of their O-specific polysaccharides, though the LPSs differ
      in their core regions.

PMID- 11335143
TI  - Elevated levels of interleukin-13 and IL-18 in patients with dengue hemorrhagic
      fever.
AB  - Interleukin (IL)-13 is produced by T helper 2 (Th2)-type cells and inhibits the
      production of proinflammatory cytokines by activated monocytes, while IL-18 is a
      pleiotropic cytokine that induces interferon-gamma and plays an important role in
      the development of Th1-type cells. Role of the shift from a Th1-type response to
      Th2-type has been suggested in the pathogenesis of dengue hemorrhagic fever
      (DHF). This study was undertaken to investigate the possible
      protective/pathogenic role of IL-13 and IL-18 in patients with DHF. Sera were
      collected from a total of 84 patients with various grades of dengue illness and
      21 normal healthy controls and tested for IL-13 and IL-18 levels using commercial
      enzyme-linked immunosorbent assay kits. The results showed that very low levels
      of IL-13 (4+/-3 pg ml(-1)) and IL-18 (15+/-4 pg ml(-1)) were detected in the sera
      of healthy controls. In dengue patients, the levels of IL-13 and IL-18 were the
      highest in the patients with DHF grade IV (205+/-103 pg ml(-1) and 366+/-155 pg
      ml(-1), respectively) and the lowest in patients with dengue fever (22+/-12 pg
      ml(-1) and 76+/-50 pg ml(-1), respectively). Both the cytokines appeared (IL
      13=20+/-11 pg ml(-1) and IL-18=70+/-45 pg ml(-1)) during the first 4 days of
      illness and reached peak levels (IL-13=204+/-96 pg ml(-1) and IL-18=360+/-148 pg
      ml(-1)) by day 9 onwards. The presence of high levels of IL-13 and IL-18 during
      severe illness and late phases of the disease suggests that both of these
      cytokines may contribute to the shift from a Th1- to Th2-type response and thus
      to the pathogenesis of DHF.

PMID- 11335144
TI  - Usage of Aplysia lectin interactions with T antigen and poly-N-acetyllactosamine
      for screening of E. coli strains which bear glycoforms cross-reacting with cancer
      associated antigens.
AB  - Aplysia gonad lectin (AGL), which strongly agglutinates cancer cells, was found,
      in the present study, to bind to erythrocyte T antigen, in addition to its
      affinity to Ii system antigens. These antigens were reported to be overexpressed
      and to contribute to tumor progression and invasion. In healthy human sera, there
      are antibodies against them, stimulated by the normal intestinal microflora,
      which bear similar glycoforms. Since the levels of these antibodies were reported
      to be lower in most cancer patients' sera, we have examined the applicability of
      AGL to isolation of enteric commensal Escherichia coli strains which bear
      glycoforms cross-reacting with the cancer-associated antigens. Among 30 E. coli
      isolates examined, two were agglutinated by AGL. One of them was also
      agglutinated by certain related galactophilic lectins, which bind to the T and Tn
      antigens. The agglutination of the two bacteria by healthy human sera, as a
      group, was stronger than that displayed by the cancer patients' sera. These
      results indicate that AGL might be useful for identification of the desired
      bacteria, which could potentially serve for cancer diagnosis and therapy.

PMID- 11335145
TI  - Priming of immune responses to hepatitis B surface antigen in young mice
      immunized in the presence of maternally derived antibodies.
AB  - Early vaccination is necessary to protect infants from various infectious
      diseases. However, this is often unsuccessful largely due to the immaturity of
      the neonatal immune system. Furthermore, maternally derived antibodies can
      interfere with active immunization. We have previously shown in young mice that
      immune responses against several different antigens can be improved by the
      addition of oligodeoxynucleotides containing immunostimulatory CpG motifs (CpG
      ODN). In this study we have evaluated immunization of newborn (1-7-day-old)
      BALB/c mice against hepatitis B surface antigen (HBsAg), with alum and/or CpG
      ODN, in the presence of high levels of maternal antibody against HBsAg (anti
      HBs). Seroconversion rates and anti-HBs titers were compared to those induced by
      a HBsAg-expressing plasmid, since other studies had suggested DNA vaccines to be
      superior to protein vaccines in young mice with maternal antibody. HBsAg/alum/CpG
      ODN was superior to DNA vaccine in inducing HBsAg-specific CTL responses in young
      mice in the presence of maternally transferred anti-HBs antibodies. However, B
      cell responses to both HBsAg/alum/CpG ODN and DNA vaccines remained weak in the
      presence of maternally transferred anti-HBs antibodies.

PMID- 11335146
TI  - The immunomodulatory effects of gentamicin, imipenem, piperacillin and
      amphotericin B on LAK effector function in vitro.
AB  - An understanding of the immunomodulating effects of anti-microbial regimens on
      recombinant interleukin-2 (rIL-2) induced peripheral leukocyte function, i.e.
      lymphokine-activated killer (LAK)-cell efficacy, would be clinically useful in
      the selection of commonly employed bone marrow transplantation (BMT) antibiotics
      to avoid post-transplant complications and optimize anti-microbial, anti-viral,
      anti-tumor therapies. In this report we evaluated the modulatory effects of a
      number of antibiotics used in BMT on LAK-cell cytotoxicities, in vitro. Our data
      showed that, even at serum trough titer, amphotericin B was significantly (P < or
      =0.05) immunostimulatory, whereas gentamicin, imipenem, and piperacillin,
      individually, were significantly (P < or =0.05) immunosuppressive. Statistical
      analysis detected no modulation due to aztreonam, amikacin, cotrimoxazole, or
      ceftazidime, or any of the six cephalosporins tested at molar equivalent
      concentration. We conclude that certain antibiotics may be more suitable for
      infection prone BMT hosts.

PMID- 11335147
TI  - EMG signal decomposition: how can it be accomplished and used?
AB  - Electromyographic (EMG) signals are composed of the superposition of the activity
      of individual motor units. Techniques exist for the decomposition of an EMG
      signal into its constituent components. Following is a review and explanation of
      the techniques that have been used to decompose EMG signals. Before describing
      the decomposition techniques, the fundamental composition of EMG signals is
      explained and after, potential sources of information from and various uses of
      decomposed EMG signals are described.

PMID- 11335148
TI  - Evaluation of intra-muscular EMG signal decomposition algorithms.
AB  - We propose and test a tool to evaluate and compare EMG signal decomposition
      algorithms. A model for the generation of synthetic intra-muscular EMG signals,
      previously described, has been used to obtain reference decomposition results. In
      order to evaluate the performance of decomposition algorithms it is necessary to
      define indexes which give a compact but complete indication about the quality of
      the decomposition. The indexes given by traditional detection theory are in this
      paper adapted to the multi-class EMG problem. Moreover, indexes related to model
      parameters are also introduced. It is possible in this way to compare the
      sensitivity of an algorithm to different signal features. An example application
      of the technique is presented by comparing the results obtained from a set of
      synthetic signals decomposed by expert operators having no information about the
      signal features using two different algorithms. The technique seems to be
      appropriate for evaluating decomposition performance and constitutes a useful
      tool for EMG signal researchers to identify the algorithm most appropriate for
      their needs.

PMID- 11335149
TI  - Human motor unit recruitment and derecruitment during long lasting intermittent
      contractions.
AB  - Seven healthy subjects were investigated in cyclic ramp-and-hold long lasting
      isometric contractions. Wire branched electrodes were used for selective
      recording of single motor unit (MU) potentials from m. biceps brachii. MU
      behaviour was defined in terms of recruitment/derecruitment thresholds (RT and
      DT) and the duration of interspike intervals (ISI). A total of 63 MUs was
      investigated: 40 units were active from the beginning of the task performance and
      another 23 were recruited later. There were no changes in the recruitment pattern
      of MUs with fatigue development - a short first ISI followed by a very long
      second one and an almost constant firing rate after this transient phase. The
      tendency of RT to gradually decrease dominates the results. Thus, the required
      constant rate of force increase with fatigue development was maintained mostly by
      the mechanisms of space coding (i.e., decrease of RT and recruitment of
      additional MUs). Oppositely, the time behaviour of the DT changes was not uniform
      and rate coding was an essential mechanism in the adaptation of MU activity to
      muscle fatigue during relaxation phases. The recruitment pattern and fatigue
      related behaviour of the additionally recruited MUs were similar to those of MUs
      active from the first cycle of the motor task performance.

PMID- 11335150
TI  - Motor unit activity during stereotyped finger tasks and computer mouse work.
AB  - Motor unit (MU) activity pattern was examined in the right-hand extensor
      digitorum communis muscle (EDC) during standardised finger movements simulating
      actual computer mouse tasks. Intramuscular recordings were performed with a
      quadripolar needle electrode. Nine women performed four lifts of their right-hand
      index finger, middle finger or both as well as a number of double clicks.
      Additionally, the subjects performed contra lateral activity with their left-hand
      fingers and for three subjects recordings were also obtained during an interview
      with no physical activity. Besides the expected close coupling of MU activity
      with finger movement, activity was observed in three different situations with no
      physical requirements. Attention related activity was found before or after
      performance of the finger movement task, contra lateral activity in right EDC
      during left-hand finger tasks, and activity during mental activity without any
      finger movements involved. A relatively large number of doublet occurrences
      suggest they are a natural part of the activation pattern during performance of
      the rapid finger movement required to perform an efficient double click on the
      computer mouse.

PMID- 11335151
TI  - Motor unit recruitment in the trapezius muscle with special reference to coarse
      arm movements.
AB  - Chronic shoulder pain is common in a variety of occupations. The "Cinderella
      hypothesis" suggests that the pain originates from damaged type I muscle fibres
      driven into degenerative processes as a result of too long activation and too
      short recovery time. The main purpose of this study was to investigate if the
      same motor units are active during all phases of coarse arm movements. Eight
      healthy volunteers participated in the study. Intramuscular electromyographic
      signals were picked up with a four-lead fine wire electrode, during a unilateral
      straight arm movement. The movement started with either (part 1) an abduction or
      a flexion, then (2) a movement in the horizontal plane from the sagittal to the
      frontal plane or vice versa, and finally (3) an adduction or an extension to the
      start position. The movement cycle was performed in three different speeds, slow,
      medium, and high, with one, two or five cycles per 20 s, respectively. On an
      average, the motor unit action potentials (MUAPs) of 6 motor units (range, 1-15)
      were identified per trail. In total 94% of the MUAP trains that were identified
      showed firings in all 3 parts of the movements. The findings support the
      Cinderella hypothesis, although there is a need to further investigate the
      temporal pattern of long-term motor unit activity.

PMID- 11335152
TI  - The role of motor unit rate modulation versus recruitment in repeated submaximal
      voluntary contractions performed by control and spinal cord injured subjects.
AB  - The relative roles of motor unit firing rate modulation and recruitment were
      evaluated when individuals with cervical spinal cord injury (SCI) and able-bodied
      controls performed a brief (6 s), 50% maximal voluntary contraction (50% MVC;
      target contraction) of triceps brachii every 10 s until it required maximal
      effort to achieve the target force. Mean (+/-SD) endurance times for SCI and
      control subjects were 34+/-26 and 15+/-5 min, respectively, at which point
      significant reductions in maximal triceps force had occurred. Twitch occlusion
      analysis in controls indicated that force declines resulted largely from
      peripheral contractile failure. In SCI subjects, triceps surface EMG and motor
      unit potential amplitude declined in parallel suggesting failure at axon branch
      points and/or alterations in muscle membrane properties. The force of low
      threshold units, measured by spike-triggered averaging, declined in SCI but not
      control subjects, suggesting that higher threshold units fatigued in controls.
      Central fatigue was also obvious after SCI. Mean (+/-SD) MVC motor unit firing
      rates declined significantly with fatigue for control (24.6+/-7.1 to 17.3+/
      5.1Hz), but not SCI subjects (25.9+/-12.7 to 20.1+/-9.7Hz). Unit firing rates
      were unchanged during target contractions for each subject group, but with the
      MVC rate decreases, units of SCI and control subjects were activated intensely at
      endurance time (88% and 99% MVC rates, respectively). New unit recruitment also
      maintained the target contractions although it was limited after SCI because many
      descending inputs to triceps motoneurons were disrupted. This resulted in sparse
      EMG, even during MVCs, but allowed the same unit to be recorded throughout. These
      EMG data showed that both unit recruitment and rate modulation were important for
      maintaining force during repeated submaximal intermittent contractions of triceps
      brachii muscles performed by SCI subjects. Similar results were found for control
      subjects. Muscles weakened by SCI may therefore provide a useful model in which
      to directly study motor unit rate modulation and recruitment during weak or
      strong voluntary contractions.

PMID- 11335153
TI  - Auxin and phyllotaxis.
AB  - Our understanding of phyllotaxis is still largely based on surgical and
      pharmacological experiments carried out before 1970. Recent experiments implicate
      the plant hormone auxin in the regulation of phyllotaxis. A recent paper shows
      how the polar auxin transport mutant, pin1-1, which fails to make flowers,
      affects the expression of well known meristem genes. This work opens the door for
      the genetic analysis of phyllotaxis.

PMID- 11335171
TI  - Enhancing photosynthesis with sugar signals.
AB  - Photosynthesis has long been a target in the quest to maximize crop productivity
      to feed burgeoning populations. Recent evidence suggests that improved
      photosynthetic performance can be most easily achieved by modifying sugar
      signalling mechanisms that control the expression of genes for whole pathways and
      processes that determine photosynthetic capacity and source-sink balance, rather
      than by directly targeting individual 'key' enzymes. Here, we highlight recent
      progress and support for the hypothesis that genetic modification of trehalose
      metabolism through its interaction with sugar-signalling pathways can enhance
      photosynthetic capacity.

PMID- 11335172
TI  - The apicoplast: a new member of the plastid family.
AB  - Protozoan parasites of the phylum Apicomplexa include pathogens such as
      Plasmodium, Toxoplasma and Cryptosporidium. They have been shown to contain a
      vestigial nonphotosynthetic plastid, the apicoplast, which might have arisen by
      secondary endosymbiosis. Little is known about the function of the apicoplast but
      the parasites exhibit delayed cell death when their apicoplast is impaired. The
      discovery of the apicoplast opens an unexpected opportunity to link current
      fundamental research on plant and algal plastids to the physiology of
      apicomplexans. For example, the apicoplast might provide new targets for
      innovative drugs that act as herbicides and do not affect the mammalian host.

PMID- 11335173
TI  - Vacuolar H(+) pyrophosphatases: from the evolutionary backwaters into the
      mainstream.
AB  - Vacuolar-type H(+)-translocating inorganic pyrophosphatases have long been
      considered to be restricted to plants and to a few species of phototrophic
      bacteria. However, in recent investigations, these pyrophosphatases have been
      found in organisms as disparate as thermophilic Archaea and parasitic protists,
      and have resulted in the definition of a novel subclass in plants themselves.
      Among the many evolutionary and practical implications of these findings is the
      possibility that this research will spawn new approaches to the treatment of
      several prolific and debilitating parasite-mediated infections.

PMID- 11335174
TI  - ORCAnization of jasmonate-responsive gene expression in alkaloid metabolism.
AB  - Jasmonic acid is an important plant stress signalling molecule. It induces the
      biosynthesis of defence proteins and protective secondary metabolites. In
      alkaloid metabolism, jasmonate acts by coordinate activation of the expression of
      multiple biosynthesis genes. In terpenoid indole alkaloid metabolism and primary
      precursor pathways, jasmonate induces gene expression and metabolism via ORCAs,
      which are members of the AP2/ERF-domain family of plant transcription factors.
      Other jasmonate-regulated (secondary) metabolic pathways might also be controlled
      by ORCA-like AP2/ERF-domain transcription factors. If so, such regulators could
      be used to improve plant fitness or metabolite productivity of plants or cell
      cultures.

PMID- 11335176
TI  - Phosphatidic acid: an emerging plant lipid second messenger.
AB  - Evidence is accumulating that phosphatidic acid is a second messenger. Its level
      increases within minutes of a wide variety of stress treatments including
      ethylene, wounding, pathogen elicitors, osmotic and oxidative stress, and
      abscisic acid. Enhanced signal levels are rapidly attenuated by phosphorylating
      phosphatidic acid to diacylglycerol pyrophosphate. Phosphatidic acid is the
      product of two signalling pathways, those of phospholipases C and D, the former
      in combination with diacylglycerol kinase. Families of these genes are now being
      cloned from plants. Several downstream targets of phosphatidic acid have been
      identified, including protein kinases and ion channels.

PMID- 11335175
TI  - Medical molecular farming: production of antibodies, biopharmaceuticals and
      edible vaccines in plants.
AB  - The use of plants for medicinal purposes dates back thousands of years but
      genetic engineering of plants to produce desired biopharmaceuticals is much more
      recent. As the demand for biopharmaceuticals is expected to increase, it would be
      wise to ensure that they will be available in significantly larger amounts, on a
      cost-effective basis. Currently, the cost of biopharmaceuticals limits their
      availability. Plant-derived biopharmaceuticals are cheap to produce and store,
      easy to scale up for mass production, and safer than those derived from animals.
      Here, we discuss recent developments in this field and possible environmental
      concerns.

PMID- 11335177
TI  - Influence of exposure concentration or dose on the distribution of particulate
      material in rat and human lungs.
AB  - Differences among species in the anatomic sites of particle retention could
      influence responses to inhaled particles. In this study, we used morphometric
      techniques to examine the influence of exposure concentration on particle
      retention in histologic sections from rats and humans. The rats had been exposed
      for 24 months to diesel exhaust at 0.35, 3.5, or 7.0 mg soot/m(3). The human
      subjects were nonsmokers who did not work as miners, nonsmoking coal miners who
      worked under the current standard of 2 mg dust/m(3) for 10-20 years (mean = 14
      years), and nonsmoking coal miners who worked under the former standard of < 10
      mg dust/m(3) for 33-50 years (mean = 40 years). The distribution of retained
      particles within the lung compartments was markedly different between species. In
      all three groups of rats, 82-85% of the retained particulate material was located
      in the alveolar and alveolar duct lumens, primarily in macrophages. In humans,
      57, 68, and 91% of the retained particulate material was located in the
      interstitium of the lung in the non-miners, coal miners under the current
      standard, and coal miners under the former standard, respectively. These results
      show that chronically inhaled diesel soot is retained predominantly in the
      airspaces of rats over a wide range of exposures, whereas in humans, chronically
      inhaled particulate material is retained primarily in the interstitium. In
      humans, the percentage of particles in the interstitium is increased with
      increased dose (exposure concentration, years of exposure, and/or lung burden).
      This difference in distribution may bring different lung cells into contact with
      the retained particles or particle-containing macrophages in rats and humans and
      may account for differences in species response to inhaled particles.

PMID- 11335178
TI  - Number concentration and size of particles in urban air: effects on spirometric
      lung function in adult asthmatic subjects.
AB  - Daily variations in ambient particulate air pollution are associated with
      variations in respiratory lung function. It has been suggested that the effects
      of particulate matter may be due to particles in the ultrafine (0.01-0.1 microm)
      size range. Because previous studies on ultrafine particles only used self
      monitored peak expiratory flow rate (PEFR), we assessed the associations between
      particle mass and number concentrations in several size ranges measured at a
      central site and measured (biweekly) spirometric lung function among a group of
      54 adult asthmatics (n = 495 measurements). We also compared results to daily
      morning, afternoon, and evening PEFR measurements done at home (n = 7,672-8,110
      measurements). The median (maximum) 24 hr number concentrations were 14,500/cm(3)
      (46,500/cm(3)) ultrafine particles and 800/cm(3) (2,800/cm(3)) accumulation mode
      (0.1-1 microm) particles. The median (maximum) mass concentration of PM(2.5)
      (particulate matter < 2.5 microm) and PM(10) (particulate matter < 10 microm in
      aerodynamic diameter) were 8.4 microg/m(3) (38.3 microg/m(3)) and 13.5
      microg/m(3) (73.7 microg/m(3)), respectively. The number of accumulation mode
      particles was consistently inversely associated with PEFR in spirometry. Inverse,
      but nonsignificant, associations were observed with ultrafine particles, and no
      associations were observed with large particles (PM(10)). Compared to the effect
      estimates for self-monitored PEFR, the effect estimates for spirometric PEFR
      tended to be larger. The standard errors were also larger, probably due to the
      lower number of spirometric measurements. The present results support the need to
      monitor the particle number and size distributions in urban air in addition to
      mass.

PMID- 11335179
TI  - Air quality in postunification Erfurt, East Germany: associating changes in
      pollutant concentrations with changes in emissions.
AB  - The unification of East and West Germany in 1990 resulted in sharp decreases in
      emissions of major air pollutants. This change in air quality has provided an
      opportunity for a natural experiment to evaluate the health impacts of air
      pollution. We evaluated airborne particle size distribution and gaseous co
      pollutant data collected in Erfurt, Germany, throughout the 1990s and assessed
      the extent to which the observed changes are associated with changes in the two
      major emission sources: coal burning for power production and residential
      heating, and motor vehicles. Continuous data for sulfur dioxide, total suspended
      particulates (TSP), nitric oxide, carbon monoxide, and meteorologic parameters
      were available for 1990-1999, and size-selective particle number and mass
      concentration measurements were made during winters of 1991 and 1998. We used
      hourly profiles of pollutants and linear regression analyses, stratified by year,
      weekday/weekend, and hour, using NO and SO(2) as markers of traffic- and heating
      related combustion sources, respectively, to study the patterns of various
      particle size fractions. Supplementary data on traffic and heating-related
      sources were gathered to support hypotheses linking these sources with observed
      changes in ambient air pollution levels. Substantially decreased (19-91%)
      concentrations were observed for all pollutants, with the exception of particles
      in the 0.01-0.03 microm size range (representing the smallest ultrafine particles
      that were measured). The number concentration for these particles increased by
      115% between 1991 and 1998. The ratio of these ultrafine particles to TSP also
      increased by more than 500%, indicating a dramatic change in the size
      distribution of airborne particles. Analysis of hourly concentration patterns
      indicated that in 1991, concentrations of SO(2) and larger particle sizes were
      related to residential heating with coal. These peaks were no longer evident in
      1998 due to decreases in coal consumption and consequent decreased emissions of
      SO(2) and larger particles. These decreases in coal combustion and the decreased
      concentrations of SO(2) and particles of larger size classes may have led to
      decreased particle scavenging and may be partially responsible for the observed
      increases in ultrafine particles. Traffic-related changes, such as increased
      numbers of trucks and increased use of diesel vehicles in Erfurt, were also
      associated with increased number concentrations of ultrafine particles. Morning
      particle peaks of all sizes were associated with NO and CO (markers for traffic)
      in both the 1991 and 1998 periods. There were significant differences in the
      ultrafine particle levels for morning hours between 1991 and 1998, suggesting
      that traffic was the cause of this increase.

PMID- 11335180
TI  - Effect of air pollution on daily mortality in Hong Kong.
AB  - In different weather conditions, constituents and concentrations of pollutants,
      personal exposure, and biologic responses to air pollution may vary. In this
      study we assessed the effects of four air pollutants on mortality in both cool
      and warm seasons in Hong Kong, a subtropical city. Daily counts of mortality, due
      to all nonaccidental causes, and cardiovascular and respiratory diseases were
      modeled with daily pollutant concentrations [24-hr means for nitrogen dioxide,
      sulfur dioxide, and particulate matter < 10 microm in aerodynamic diameter
      (PM(10)); 8-hr mean for ozone]. using Poisson regression. We controlled for
      confounding factors by fitting the terms in models, in line with those
      recommended by the APHEA (Air Pollution and Health: a European Approach)
      protocol. Exposure-response relationships in warm and cool seasons were examined
      using generalized additive modeling. During the cool season, for a linear
      extrapolation of 10th-90th percentiles in the pollutant concentrations of all
      oxidant pollutants, NO(2), SO(2), and O(3), we found significant effects on all
      the mortality outcomes under study, with relative risks (RR) of 1.04-1.10 (p <
      0.038, except p = 0.079 for SO(2) on respiratory mortality). We observed
      consistent positive exposure-response relationships during the cool season but
      not during the warm season. The effects of PM(10) were marginally significant (RR
      = 1.06; p = 0.054) for respiratory mortality but not for the other outcomes (p >
      0.135). In this subtropical city, local air quality objectives should take into
      account that air pollution has stronger health effects during the cool rather
      than warm season and that oxidant pollutants are more important indicators of
      health effects than particulates.

PMID- 11335181
TI  - Fine particulate matter and polycyclic aromatic hydrocarbon concentration
      patterns in Roxbury, Massachusetts: a community-based GIS analysis.
AB  - Given an elevated prevalence of respiratory disease and density of pollution
      sources, residents of Roxbury, Massachusetts, have been interested in better
      understanding their exposures to air pollution. To determine whether local
      transportation sources contribute significantly to exposures, we conducted a
      community-based pilot investigation to measure concentrations of fine particulate
      matter (particulate matter < 2.5 microm; PM(2.5)) and particle-bound polycyclic
      aromatic hydrocarbons (PAHs) in Roxbury in the summer of 1999. Community members
      carried portable monitors on the streets in a 1-mile radius around a large bus
      terminal to create a geographic information system (GIS) map of concentrations
      and gathered data on site characteristics that could predict ambient
      concentrations. Both PM(2.5) and PAH concentrations were greater during morning
      rush hours and on weekdays. In linear mixed-effects regressions controlling for
      temporal autocorrelation, PAH concentrations were significantly higher with
      closer proximity to the bus terminal (p < 0.05), and both pollutants were
      elevated, but not statistically significantly so, on bus routes. Regressions on a
      subset of measurements for which detailed site characteristics were gathered
      showed higher concentrations of both pollutants on roads reported to have heavy
      bus traffic. Although a more comprehensive monitoring protocol would be needed to
      develop robust predictive functions for air pollution, our study demonstrates
      that pollution patterns in an urban area can be characterized with limited
      monitoring equipment and that university-community partnerships can yield
      relevant exposure information.

PMID- 11335182
TI  - Investigating regional differences in short-term effects of air pollution on
      daily mortality in the APHEA project: a sensitivity analysis for controlling long
      term trends and seasonality.
AB  - Short-term effects of air pollution on daily mortality in eight western and five
      central-eastern European countries have been reported previously, as part of the
      APHEA project. One intriguing finding was that the effects were lower in central
      eastern European cities. The analysis used sinusoidal terms for seasonal control
      and polynomial terms for meteorologic variables, but this is a more rigid
      approach than the currently accepted method, which uses generalized additive
      models (GAM). We therefore reanalyzed the original data to examine the
      sensitivity of the results to the statistical model. The data were identical to
      those used in the earlier analyses. The outcome was the daily total number of
      deaths, and the pollutants analyzed were black smoke (BS) and sulfur dioxide
      (SO(2)). The analyses were restricted to days with pollutant concentration < 200
      microg/m(3) and < 150 microg/m(3) alternately. We used Poisson regression in a
      GAM model, and combined individual city regression coefficients using fixed and
      random-effect models. An increase in BS by 50 microg/m(3) was associated with a
      2.2% and 3.1% increase in mortality when analysis was restricted to days < 200
      microg/m(3) and < 150 microg/m(3), respectively. The corresponding figures were
      5.0% and 5.6% for a similar increase in SO(2). These estimates are larger than
      the ones published previously: by 69% for BS and 55% for SO(2). The increase
      occurred only in central-eastern European cities. The ratio of western to central
      eastern cities for estimates was reduced to 1.3 for BS (previously 4.8) and 2.6
      for SO(2) (previously 4.4). We conclude that part of the heterogeneity in the
      estimates of air pollution effects between western and central-eastern cities
      reported in previous publications was caused by the statistical approach used and
      the inclusion of days with pollutant levels above 150 microg/m(3). However, these
      results must be investigated further.

PMID- 11335183
TI  - Effects of temperature and air pollutants on cardiovascular and respiratory
      diseases for males and females older than 65 years of age in Tokyo, July and
      August 1980-1995.
AB  - We studied exposures to higher daily maximum temperatures and concentrations of
      air pollutants in Tokyo during the summer months of July and August from 1980 to
      1995 and their effects on hospital emergency transports for cardiovascular and
      respiratory diseases for males and females > 65 years of age. Cardiovascular
      diseases were angina, cardiac insufficiency, hypertension, and myocardial
      infarction. Respiratory diseases were asthma, acute and chronic bronchitis, and
      pneumonia. Except for pneumonia, daily maximum temperatures were not associated
      with hospital emergency transports. Increasing daily maximum temperatures,
      however, were associated with decreased hospital emergency transports for
      hypertension. Concentrations of nitrogen dioxide or particulate matter < or = 10
      microm, however, were associated with daily hospital emergency transports for
      angina, cardiac insufficiency, myocardial infarction, asthma, acute and chronic
      bronchitis, and pneumonia. For cardiac insufficiency, hypertension, myocardial
      infarction, asthma, chronic bronchitis, and pneumonia, the expected daily number
      of emergency transports per million were greater for males than for females. For
      angina and acute bronchitis, there were no differences for the expected daily
      numbers of emergency transports per million between males and females.

PMID- 11335184
TI  - Characterization of toxicokinetics and toxicodynamics with linear systems theory:
      application to lead-associated cognitive decline.
AB  - We present a theoretical approach to analysis of toxicokinetics and
      toxicodynamics using linear systems theory. In our approach, we define two
      impulse response functions that characterize the kinetic behavior of an
      environmental agent in the body and the dynamic time-course behavior of its
      effect on the body. This approach provides a formalism for understanding the
      relation among exposure, dose, and cumulative biologically effective dose and for
      understanding the implications of an effect time-course on cross-sectional and
      longitudinal data analyses. We use lead-associated cognitive decline as a
      specific example where the approach may be applied.

PMID- 11335186
TI  - The red tide toxin, brevetoxin, induces embryo toxicity and developmental
      abnormalities.
AB  - Brevetoxins are lipophilic polyether toxins produced by the red tide
      dinoflagellate Gymnodinium breve, and their neurotoxic effects on adult animals
      have been documented. In this study, we characterized adverse developmental
      effects of brevetoxin-1 (PbTx-1) using an exposure paradigm that parallels the
      maternal oocyte transfer of toxin. Medaka fish (Oryzias latipes) embryos were
      exposed to PbTx-1 via microinjection of toxin reconstituted in a triolein oil
      droplet. Embryos microinjected with doses of 0.1-8.0 ng/egg (ppm) of brevetoxin-1
      exhibited pronounced muscular activity (hyperkinesis) after embryonic day 4. Upon
      hatching, morphologic abnormalities were commonly found in embryos at the
      following lowest adverse effect levels: 1.0-3.0 ppm, lateral curvature of the
      spinal column; 3.1-3.4 ppm, herniation of brain meninges through defects in the
      skull; and 3.4-4.0 ppm, malpositioned eye. Hatching abnormalities were also
      commonly observed at brevetoxin doses of 2.0 ppm and higher with head-first, as
      opposed to the normal tail-first, hatching, and doses > 4.1 ng/egg produced
      embryos that developed but failed to hatch. Given the similarity of developmental
      processes found between higher and lower vertebrates, teratogenic effects of
      brevetoxins have the potential to occur among different phylogenetic classes. The
      observation of developmental abnormalities after PbTx-1 exposure identifies a new
      spectrum of adverse effects that may be expected to occur following exposure to
      G. breve red tide events.

PMID- 11335185
TI  - Pharmacogenetic profile of xenobiotic enzyme metabolism in survivors of the
      Spanish toxic oil syndrome.
AB  - In 1981, the Spanish toxic oil syndrome (TOS) affected more than 20,000 people,
      and over 300 deaths were registered. Assessment of genetic polymorphisms on
      xenobiotic metabolism would indicate the potential metabolic capacity of the
      victims at the time of the disaster. Thus, impaired metabolic pathways may have
      contributed to the clearance of the toxicant(s) leading to a low detoxification
      or accumulation of toxic metabolites contributing to the disease. We conducted a
      matched case-control study using 72 cases (54 females, 18 males) registered in
      the Official Census of Affected Patients maintained by the Spanish government.
      Controls were nonaffected siblings (n =72) living in the same household in 1981
      and nonaffected nonrelatives (n = 70) living in the neighborhood at that time,
      with no ties to TOS. Genotype analyses were performed to assess the metabolic
      capacity of phase I [cytochrome P450 1A1 (CYP1A1), CYP2D6] and phase II
      [arylamine N-acetyltransferase-2 (NAT2), GSTM1 (glutathione S-transferase M1) and
      GSTT1] enzyme polymorphisms. The degree of association of the five metabolic
      pathways was estimated by calculating their odds ratios (ORs) using conditional
      logistic regression analysis. In the final model, cases compared with siblings
      (72 pairs) showed no differences either in CYP2D6 or CYP1A1 polymorphisms, or in
      conjugation enzyme polymorphisms, whereas cases compared with the unrelated
      controls (70 pairs) showed an increase in NAT2 defective alleles [OR = 6.96, 95%
      confidence interval (CI), 1.46-33.20] adjusted by age and sex. Glutathione
      transferase genetic polymorphisms (GSTM1, GSTT1) showed no association with cases
      compared with their siblings or unrelated controls. These findings suggest a
      possible role of impaired acetylation mediating susceptibility in TOS.

PMID- 11335187
TI  - Associations of blood pressure and hypertension with lead dose measures and
      polymorphisms in the vitamin D receptor and delta-aminolevulinic acid dehydratase
      genes.
AB  - Evidence suggests that lead and selected genes known to modify the toxicokinetics
      of lead--namely, those for the vitamin D receptor (VDR) and delta-aminolevulinic
      acid dehydratase (ALAD)--may independently influence blood pressure and
      hypertension risk. We report the relations among ALAD and VDR genotypes, three
      lead dose measures, and blood pressure and hypertension status in 798 Korean lead
      workers and 135 controls without occupational exposure to lead. Lead dose was
      assessed by blood lead, tibia lead measured by X-ray fluorescence, and
      dimercaptosuccinic acid (DMSA)-chelatable lead. Among lead workers, 9.9% (n = 79)
      were heterozygous for the ALAD(2) allele, and there were no ALAD(2) homozygotes;
      11.2% (n = 89) had at least one copy of the VDR B allele, and 0.5% (n = 4) had
      the BB genotype. In linear regression models to control for covariates, VDR
      genotype (BB and Bb vs. bb), blood lead, tibia lead, and DMSA-chelatable lead
      were all positive predictors of systolic blood pressure. On average, lead workers
      with the VDR B allele, mainly heterozygotes, had systolic blood pressures that
      were 2.7-3.7 mm Hg higher than did workers with the bb genotype. VDR genotype was
      also associated with diastolic blood pressure; on average, lead workers with the
      VDR B allele had diastolic blood pressures that were 1.9-2.5 mm Hg higher than
      did lead workers with the VDR bb genotype (p = 0.04). VDR genotype modified the
      relation of age with systolic blood pressure; compared to lead workers with the
      VDR bb genotype, workers with the VDR B allele had larger elevations in blood
      pressure with increasing age. Lead workers with the VDR B allele also had a
      higher prevalence of hypertension compared to lead workers with the bb genotype
      [adjusted odds ratio (95% confidence interval) = 2.1 (1.0, 4.4), p = 0.05]. None
      of the lead biomarkers was associated with diastolic blood pressure, and tibia
      lead was the only lead dose measure that was a significant predictor of
      hypertension status. In contrast to VDR, ALAD genotype was not associated with
      the blood pressure measures and did not modify associations of the lead dose
      measures with any of the blood pressure measures. To our knowledge, these are the
      first data to suggest that the common genetic polymorphism in the VDR is
      associated with blood pressure and hypertension risk. We speculate that the BsmI
      polymorphism may be in linkage disequilibrium with another functional variant at
      the VDR locus or with a nearby gene.

PMID- 11335188
TI  - Mixtures of four organochlorines enhance human breast cancer cell proliferation.
AB  - In view of the large differences between the concentrations of estrogenic
      chemicals needed to elicit effects in in vitro assays and their levels in human
      tissues, it is hard to explain possible health risks in terms of exposure to
      individual compounds. Human populations, however, are exposed to mixtures of
      estrogenic and estrogen-like agents and it is necessary to consider the impact of
      combined effects. We assessed the combined effects of 1-(o-chlorophenyl)-1-(p
      chlorophenyl)-2,2,2-trichloroethane (o,p'-DDT), 2,2-bis(p-chlorophenyl)-1,1
      dichloroethylene (p,p'-DDE), beta-hexachlorocyclohexane (beta-HCH), and 1,1-bis(p
      chlorophenyl)-2,2,2-trichloroethane (p,p'-DDT) on the induction of cell
      proliferation in MCF-7 cells. All four compounds are persistent organochlorines
      that can be found in human tissues. We performed extensive concentration-response
      analyses with the single agents to predict the effects of two mixtures of all
      four compounds with different mixture ratios. We calculated the predictions by
      using the pharmacologically well-founded models of concentration addition and
      independent action and then tested them experimentally. o,p'-DDT, p,p'-DDE, beta
      HCH, and p,p'-DDT acted together to produce proliferative effects in MCF-7 cells.
      The combined effect of the four agents could be predicted on the basis of data
      about single agent concentration-response relationships. Regression analysis
      demonstrated that there were combination effects even when each mixture component
      was present at levels at or below its individual no-observed-effect
      concentration. We assessed combination effects in two ways: First, evaluations in
      relation to the proliferative responses induced by single mixture components
      revealed that the combination effects were stronger than the effects of the most
      potent constituent. Thus, according to this method of evaluation, the combined
      effects may be termed synergistic. Second, comparisons with the expected effects,
      as predicted by concentration addition and independent action, showed excellent
      agreement between prediction and observation. With this approach, the combined
      effect of all four compounds can be termed additive.

PMID- 11335190
TI  - Annoyance from transportation noise: relationships with exposure metrics DNL and
      DENL and their confidence intervals.
AB  - We present a model of the distribution of noise annoyance with the mean varying
      as a function of the noise exposure. Day-night level (DNL) and day-evening-night
      level (DENL) were used as noise descriptors. Because the entire annoyance
      distribution has been modeled, any annoyance measure that summarizes this
      distribution can be calculated from the model. We fitted the model to data from
      noise annoyance studies for aircraft, road traffic, and railways separately.
      Polynomial approximations of relationships implied by the model for the
      combinations of the following exposure and annoyance measures are presented: DNL
      or DENL, and percentage "highly annoyed" (cutoff at 72 on a scale of 0-100),
      percentage "annoyed" (cutoff at 50 on a scale of 0-100), or percentage (at least)
      "a little annoyed" (cutoff at 28 on a scale of 0-100). These approximations are
      very good, and they are easier to use for practical calculations than the model
      itself, because the model involves a normal distribution. Our results are based
      on the same data set that was used earlier to establish relationships between DNL
      and percentage highly annoyed. In this paper we provide better estimates of the
      confidence intervals due to the improved model of the relationship between
      annoyance and noise exposure. Moreover, relationships using descriptors other
      than DNL and percentage highly annoyed, which are presented here, have not been
      established earlier on the basis of a large dataset.

PMID- 11335189
TI  - In vitro estrogenicity of polybrominated diphenyl ethers, hydroxylated PDBEs, and
      polybrominated bisphenol A compounds.
AB  - Polybrominated diphenyl ethers (PBDEs) are used in large quantities as additive
      flame retardants in plastics and textile materials. PBDEs are persistent
      compounds and have been detected in wildlife and in human adipose tissue and
      plasma samples. In this study, we investigated the (anti)estrogenic potencies of
      several PBDE congeners, three hydroxylated PBDEs (HO-PBDEs), and differently
      brominated bisphenol A compounds in three different cell line assays based on
      estrogen receptor (ER)-dependent luciferase reporter gene expression. In human
      T47D breast cancer cells stably transfected with an estrogen-responsive
      luciferase reporter gene construct (pEREtata-Luc), 11 PBDEs showed estrogenic
      potencies, with concentrations leading to 50% induction (EC(50)) varying from 2.5
      to 7.3 microM. The luciferase induction of the most potent HO-PBDE [2-bromo-4
      (2,4,6-tribromophenoxy)phenol] exceeded that of estradiol (E(2)), though at
      concentrations 50,000 times higher. As expected, brominated bisphenol A compounds
      with the lowest degree of bromination showed highest estrogenic potencies (EC(50)
      values of 0.5 microM for 3-monobromobisphenol A). In an ER alpha-specific, stably
      transfected human embryonic kidney cell line (293-ER alpha-Luc), the HO-PBDE 4
      (2,4,6-tribromophenoxy)phenol was a highly potent estrogen with an EC(50) < 0.1
      microM and a maximum 35- to 40-fold induction, which was similar to E(2). In an
      analogous ER beta-specific 293-ER betas-Luc cell line, the agonistic potency of
      the 4-(2,4,6-tribromophenoxy)phenol was much lower (maximum 50% induction
      compared to E(2)), but EC(50) values were comparable. These results indicate that
      several pure PBDE congeners, but especially HO-PBDEs and brominated bisphenol A
      analogs, are agonists of both ER alpha and ER beta receptors, thus stimulating ER
      mediated luciferase induction in vitro. These data also suggest that in vivo
      metabolism of PBDEs may produce more potent pseudoestrogens.

PMID- 11335192
TI  - The virtual body workshop: current and future application of human biology models
      in environmental health research.

PMID- 11335191
TI  - Measurement of organophosphate metabolites in postpartum meconium as a potential
      biomarker of prenatal exposure: a validation study.
AB  - Experimental data have linked exposure to prenatal organophosphates to adverse
      neurocognitive sequalae. However, epidemiologic research has been hampered by
      lack of reliable dosimeters. Existing biomarkers reflect short-term exposure
      only. Measurements of pesticides in postpartum meconium may yield a longer-term
      dosimeter of prenatal exposure. As the initial step in biomarker validation, this
      research determined background levels, detection limits, and stabilities of six
      organophosphate metabolites in meconium: diethylphosphate (DEP),
      diethylthiophosphate (DETP), diethyldithiophosphate (DEDTP), dimethylphosphate
      (DMP), dimethylthiophosphate (DMTP), and dimethyldithiophosphate (DMDTP).
      Calibration curves were also constructed. The meconium was collected from 20
      newborns at New York Presbyterian Hospital; analyses were undertaken at the
      Centers for Disease Control and Prevention (CDC). DEP was detected in 19/20
      samples (range 0.8-3.2 microg/g) and DETP was detected in 20/20 (range 2.0-5.6
      microg/g). DMP and DEDTP were each detected in 1/20 (at 16 and 1.8 microg/g,
      respectively). DMTP and DMDTP were not detected. Detection limits were comparable
      to or lower than those in urine; levels were similar to those seen in adult urine
      in population-based research. Metabolites were stable at room temperature over 12
      hr. Calibration curves were linear over the range tested (0.5-400 microg/g);
      recoveries ranged from 18% to 66%. Using isotope dilution, recoveries of each
      analyte in individual samples can be corrected automatically based on the
      recovery of the respective stable isotope-labeled analogue, making this method
      fully quantitative. Results indicate that measurements of organophosphate
      metabolites in meconium have promise as biomarkers of prenatal exposure. Further
      research is needed to determine the time frame of exposure represented by
      pesticide levels in meconium and to evaluate the dose-response relationship.

PMID- 11335193
TI  - International conference on environmental and occupational lung diseases.

PMID- 11335194
TI  - Lead poisoning from homemade wine: a case study.
AB  - A 66-year-old man suffered the symptoms of severe lead poisoning for 2 years
      before diagnosis. The man had a blood lead level (PbB) on admission to hospital
      of 98 microg/dL. A detailed investigation revealed that the poisoning occurred as
      a result of drinking a homemade red wine, for which analyses showed a lead
      concentration up to 14 mg/L--70 times the Australian maximum limit for lead in
      wine. The source of the lead was a highly corroded enamel bathtub in which grape
      crushings and juice were stored for a week prior to bottling. The corrosion of
      the enamel surface of the bathtub had resulted in pitted patches up to 1 mm in
      depth along the side of the bathtub. Powdering of the tub surface was evident
      below a level where wine had been in contact with the sides of the tub. The
      homemade wine had a pH of 3.8, which would have greatly contributed to the
      solubilization of metals from the glaze. We conducted a test in which commercial
      red wine of similar pH and containing < 0.2 mg/L lead was placed in this tub for
      7 days. Subsequent testing revealed a lead level of 310 mg/L. This high lead
      concentration is consistent with the surface area of enamel on the bathtub being
      in contact with a small liquid volume as in the case of the leaching test using
      commercial red wine. This case study highlights the importance of the use of food
      grade materials for the preparation and storage of homemade beverages or food.

PMID- 11335195
TI  - Cold war, hot nukes: legacy of an era.

PMID- 11335196
TI  - Rededication of service to developing countries.

PMID- 11335197
TI  - OPs cause bad trips?

PMID- 11335198
TI  - Hot new report on climate change.

PMID- 11335199
TI  - Australia cuts cadmium in food.

PMID- 11335200
TI  - The future of fresh water.

PMID- 11335201
TI  - A wave of momentum for toxic algae study.

PMID- 11335202
TI  - Stopping the scourge: tobacco control goes global.

PMID- 11335203
TI  - Titanium dioxide: environmental white knight?

PMID- 11335204
TI  - A model of spirituality for psychotherapy and other fields of mind-body medicine.
AB  - The spiritual revolution that has permeated our culture challenges
      psychotherapists and other health practitioners to address the spiritual concerns
      of their clients and themselves. This challenge is particularly critical in view
      of the confused, meaningless, and faulty so-called "spiritual" ideas that affect
      some clients in ways that are toxic to their psychological (and possibly
      physical) health. However, given the nonspiritual tradition of professional
      psychology and medicine as a whole, practitioners as a group have no clear and
      cogent concept or standards with which to acknowledge and address these concerns.
      The aim of this article is to formulate a concept of spirituality that allows
      practitioners to include spirituality in their work in a clear, sound, and
      meaningful way.

PMID- 11335205
TI  - Should a doctor ask about a patient's spiritual beliefs?

PMID- 11335207
TI  - Social relationships and health: challenges for measurement and intervention.

PMID- 11335208
TI  - "The courage to change and the serenity to accept"--Further comments on fighting
      spirit and breast cancer.

PMID- 11335210
TI  - A challenge to the mind-body health movement.

PMID- 11335212
TI  - Emergency medicine research--a time to celebrate, contemplate, and propagate.

PMID- 11335213
TI  - Growing pains.

PMID- 11335689
TI  - Double agents and breakdown of integrity at the neuromuscular junction in Miller
      Fisher syndrome.

PMID- 11335690
TI  - Frontal lobes and human memory: insights from functional neuroimaging.
AB  - The new functional neuroimaging techniques, PET and functional MRI (fMRI), offer
      sufficient experimental flexibility and spatial resolution to explore the
      functional neuroanatomical bases of different memory stages and processes. They
      have had a particular impact on our understanding of the role of the frontal
      cortex in memory processing. We review the insights that have been gained, and
      attempt a synthesis of the findings from functional imaging studies of working
      memory, encoding in episodic memory and retrieval from episodic memory. Though
      these different aspects of memory have usually been studied in isolation, we
      suggest that there is sufficient convergence with respect to frontal activations
      to make such a synthesis worthwhile. We concentrate in particular on three
      regions of the lateral frontal cortex--ventrolateral, dorsolateral and anterior-
      that are consistently activated in these studies, and attribute these activations
      to the updating/maintenance of information, the selection/manipulation/monitoring
      of that information, and the selection of processes/subgoals, respectively. We
      also acknowledge a number of empirical inconsistencies associated with this
      synthesis, and suggest possible reasons for these. More generally, we predict
      that the resolution of questions concerning the functional neuroanatomical
      subdivisions of the frontal cortex will ultimately depend on a fuller cognitive
      psychological fractionation of memory control processes, an enterprise that will
      be guided and tested by experimentation. We expect that the neuroimaging
      techniques will provide an important part of this enterprise.

PMID- 11335691
TI  - Neuropathological abnormalities in schizophrenia: evidence from magnetization
      transfer imaging.
AB  - Post-mortem and structural brain imaging studies in schizophrenia have reported
      macroscopic changes such as global and regional cortical volume reductions, but
      it has been more difficult to characterize the histopathological changes that
      underlie these abnormalities. Magnetization transfer imaging (MTI), a novel MRI
      technique, more sensitive to subtle or early neuropathological changes than
      conventional MRI, provides a quantitative measure of macromolecular structural
      integrity represented by the magnetization transfer ratio (MTR). In this study,
      we used MTI to examine 25 patients with schizophrenia compared with 30 age
      matched controls. A voxel-based analysis of the MTR maps revealed widespread MTR
      reductions in the cortex unrelated to volume reduction, predominantly in the
      frontal and temporal regions, in the schizophrenic patients when compared with
      controls. MTR reductions in bilateral parieto-occipital cortex and the genu of
      the corpus callosum were associated with the severity of negative symptoms in the
      schizophrenic patients. However, MTR changes were not related to other clinical
      variables of age, duration of illness and current dose of antipsychotic
      medication. This study demonstrates that MTR abnormalities in the cortex can be
      detected in chronic schizophrenia that may reflect subtle neuropathological
      changes involving neurones or neuronal processes. Longitudinal studies are needed
      to determine whether these abnormalities are related to disease progression or
      other disease manifestations such as cognitive changes.

PMID- 11335692
TI  - Anti-GQ1b ganglioside antibodies mediate complement-dependent destruction of the
      motor nerve terminal.
AB  - Miller-Fisher syndrome is an autoimmune neuropathy characterized by ataxia,
      areflexia and ophthalmoplegia, and in the majority of cases the presence of high
      titres of anti-GQ1b ganglioside antibodies. In an ex vivo model, human and mouse
      anti-GQ1b antibodies have been shown previously to induce a complement-dependent
      alpha-latrotoxin-like effect on the murine motor endplate, i.e. they bring about
      massive quantal release of acetylcholine and eventually block neuromuscular
      transmission. Using immunofluorescence microscopy with image analysis, we show
      here that the late stages of this electrophysiological effect temporally coincide
      with the loss of heavy neurofilament (200 kDa) and type III beta-tubulin
      immunostaining and structural breakdown of the nerve terminal, as demonstrated by
      electron microscopy. Ultrastructurally, axon terminals were disorganized,
      depleted of vesicles, and subdivided by the infiltrating processes of capping
      Schwann cells. These findings provide clear pathological evidence to support a
      role for anti-ganglioside antibodies in mediating nerve terminal injury and
      further advance the view that this site may be of importance as a target in some
      human neuropathies.

PMID- 11335693
TI  - Mutations in the 5' region of the myotubularin-related protein 2 (MTMR2) gene in
      autosomal recessive hereditary neuropathy with focally folded myelin.
AB  - Focally folded myelin has been recognized as a distinctive feature in some
      individuals with severe inherited demyelinating neuropathy, with an onset in
      childhood. Such cases have been shown to be genetically heterogeneous.
      Alterations in the myotubularin-related protein 2 (MTMR2) gene on chromosome
      11q22 have recently been shown to give rise to this phenotype. Mutations have
      been identified in the 3' region of the MTMR2 gene in four unrelated families, in
      two of whom the disorder had been mapped to chromosome 11q22 by genetic linkage
      analysis. We have sequenced the entire coding region and flanking intronic
      regions of the MTMR2 gene in eight families with early onset autosomal recessive
      neuropathies. Two novel mutations were identified in exon 4 at the 5' end of the
      MTMR2 gene in an English and an Indian family. The clinical phenotype and sural
      nerve pathology in these two families differs in severity, with the proband in
      the English family having an earlier onset and more severe neuropathy with
      prominent cranial nerve involvement. This is probably due to mutation type and
      possible involvement of small nucleotide polymorphisms in phenotype modulation.
      Detailed sural nerve pathology is presented in both cases. Mutations in the MTMR2
      gene are thus an important cause of autosomal recessive demyelinating neuropathy.
      Identifying further mutations and defining their phenotype will help to clarify
      the genetic classification of this group of disorders.

PMID- 11335694
TI  - Cortical activation by tactile and painful stimuli in hemispherectomized
      patients.
AB  - Hemispherectomized patients are able to perceive tactile and painful stimuli on
      their nonparetic as well as paretic body halves. We have used functional MRI to
      study the cortical mechanisms underlying this preserved somatosensory capacity.
      Nonpainful brushing and painful heat were applied to the skin of the legs in four
      hemispherectomized patients and, for comparison, in four normal subjects.
      Cortical activation was studied with a 1.5 T scanner using a BOLD (blood oxygen
      level dependent) protocol. All patients rated both the brushing and the heat pain
      as almost equally intense on each leg and the ratings were similar to those in
      normals. Brushing on the nonparetic leg activated primary and secondary
      somatosensory cortices (S1 and S2) in all patients, similar to findings in
      normals. Brushing on the paretic leg activated S1 in two patients and S2 in one
      of these patients. Heat pain activated S2, insular cortex and anterior cingulate
      cortex to a similar degree for both legs, but the activation was weaker in the
      patients than in the normals. For the individual patient, there was generally no
      obvious correlation between cortical activation as studied with the BOLD
      technique and psychophysical performance. The findings from tactile stimulation
      of the nonparetic leg, that the activation was similar to the contralateral
      activation in normals, suggest that tactile information processing in the
      hemisphere contralateral to the stimulation is independent of the corpus
      callosum. In contrast, the pain activation for the nonparetic leg was weaker than
      in normals, suggesting that pain activation in the hemisphere contralateral to
      the stimulation is dependent on transcallosal information processing. The latter
      finding was corroborated by a subnormal capacity for pain localization on the
      nonparetic foot in two of the patients. The findings from stimulation of the
      paretic leg show that areas typically involved in the processing of tactile and
      painful stimuli can be activated by ipsilateral pathways directly from the
      periphery. The tactile-evoked ipsilateral S1 activation may be due to subcortical
      reorganization, since it was not observed in the normal subjects.

PMID- 11335695
TI  - Cortical deafness to dissonance.
AB  - Ordinary listeners, including infants, easily distinguish consonant from
      dissonant pitch combinations and consider the former more pleasant than the
      latter. The preference for consonance over dissonance was tested in a patient,
      I.R., who suffers from music perception and memory disorders as a result of
      bilateral lesions to the auditory cortex. In Experiment 1, I.R. was found to be
      unable to distinguish consonant from dissonant versions of musical excerpts taken
      from the classical repertoire by rating their pleasantness. I.R.'s indifference
      to dissonance was not due to a loss of all affective responses to music, however,
      since she rated the same excerpts as happy or sad, as normal controls do. In
      Experiment 2, I.R.'s lack of responsiveness to varying degrees of dissonance was
      replicated with chord sequences which had been used in a previous study using
      PET, in examining emotional responses to dissonance. A CT scan of I.R.'s brain
      was co-registered with the PET activation data from normal volunteers. Comparison
      of I.R.'s scan with the PET data revealed that the damaged areas overlapped with
      the regions identified to be involved in the perceptual analysis of the musical
      input, but not with the paralimbic regions involved in affective responses. Taken
      together, the findings suggest that dissonance may be computed bilaterally in the
      superior temporal gyri by specialized mechanisms prior to its emotional
      interpretation.

PMID- 11335696
TI  - Impaired spatial working memory across saccades contributes to abnormal search in
      parietal neglect.
AB  - Visual neglect of left space following right parietal damage in humans involves a
      lateral bias in attention, apparent in many search tasks. We hypothesized that
      parietal neglect may also involve a failure to remember which locations have
      already been examined during visual search: an impairment in retaining searched
      locations across saccades. Using a new paradigm, we monitored gaze during search,
      while simultaneously probing whether observers judged they had found a new
      target, or judged instead that they were re-fixating a previously examined
      target. A patient with left neglect following focal right parietal infarction
      repeatedly re-fixated right locations. Critically, he often failed to remember
      that these locations had already been searched, treating old targets as new
      discoveries at an abnormal rate. In comparison, healthy age-matched control
      subjects rarely re-fixated targets, and mistook old targets as new targets even
      more rarely. The frequency of such mistakes in the parietal patient, for
      different conditions, correlated with the severity of his neglect. Control
      experiments indicated no perceptual localization deficit in non-search tasks.
      These results suggest a deficit in retaining searched locations across saccades
      in parietal neglect, in addition to the lateral spatial bias. Moreover, the
      former deficit exacerbates the latter, such that patients do not realize that the
      rightward locations favoured by their bias have already been examined during
      previous fixations and, for this reason, they saccade back to them repeatedly.
      The combination of the two deficits (a lateral bias plus a deficit in retaining
      locations already searched) may thus explain the pathological pattern of search
      that characterizes parietal neglect: why stimuli on the right are re-examined
      recursively, as if being searched for the first time, and hence why stimuli on
      the left continue to be ignored even with unlimited viewing time. These proposals
      accord with recent electrophysiological and functional imaging data,
      demonstrating posterior parietal involvement in the retention of target locations
      across saccades.

PMID- 11335697
TI  - Proton MR spectroscopy with metabolite-nulling reveals elevated macromolecules in
      acute multiple sclerosis.
AB  - Proton magnetic resonance spectroscopy has shown elevated signals in the spectral
      region of lipids in acute multiple sclerosis lesions. The metabolite-nulling
      technique allows the separation of macromolecules from other metabolites, such as
      lactate, N-acetyl-aspartate, creatine, choline and myo-inositol. Using this
      technique in studies on multiple sclerosis patients, we were able to
      differentiate macromolecules biochemically in acute and chronic multiple
      sclerosis lesions. Ten patients with acute, contrast-enhancing multiple sclerosis
      lesions, 10 patients with chronic lesions and 10 healthy control subjects were
      investigated with a 1.5 T whole body system, using a stimulated echo acquisition
      mode (STEAM) sequence with metabolite-nulling and outer volume saturation.
      Metabolites and macromolecules were quantitated absolutely. The 0.9 and 1.3 parts
      per million (p.p.m.) resonances of the macromolecules were significantly elevated
      in acute lesions compared with chronic lesions and healthy controls (P < 0.001
      for 0.9 p.p.m., P < 0.05 for 1.3 p.p.m.). The macromolecular resonances at 2.1
      and 3.0 p.p.m. in acute and chronic lesions were normal. N-acetyl-aspartate was
      significantly reduced in acute and chronic lesions compared with controls (P <
      0.05 and P < 0.01, respectively). Choline was significantly elevated in acute
      lesions compared with controls (P < 0.05). Up to now, elevated resonances at 0.9
      and 1.3 p.p.m. in acute lesions have been interpreted as lipids. In metabolite
      nulled spectra, the macromolecular resonances did not fit those of lipids and
      might have been due to proteins or polypeptides containing the amino acids
      alanine, threonine, valine, leucine and isoleucine. These account for
      approximately 40% of the amino acids of myelin proteolipid protein and for
      approximately 20% of myelin basic protein. The increased macromolecular
      resonances at 0.9 and 1.3 p.p.m. may be interpreted as biochemical markers of
      myelin fragments and may be used as reliable markers of acute multiple sclerosis
      lesions as they provide clear discrimination among acute and chronic lesions and
      controls.

PMID- 11335698
TI  - The Multiple Sclerosis Impact Scale (MSIS-29): a new patient-based outcome
      measure.
AB  - Changes in health policy have underlined the importance of evidence-based
      clinical practice and rigorous evaluation of patient-based outcomes. As patient
      based outcome measurement is particularly important in treatment trials of
      multiple sclerosis, a number of disease-specific instruments have been developed
      recently. One limitation of these instruments is that none was developed using
      the standard psychometric approach of reducing a large item pool generated from
      people with multiple sclerosis. Consequently, an outcome measure for clinical
      trials of multiple sclerosis that is disease specific and combines patient
      perspective with rigorous psychometric methods will complement existing
      instruments. The aim of this study was to develop such a measure. Standard
      psychometric methods were used. A pool of 129 questionnaire items was generated
      from interviews with 30 people with multiple sclerosis, expert opinion and
      literature review. The questionnaire was administered by postal survey to 1530
      people selected randomly from the Multiple Sclerosis Society membership database.
      Redundant items and those with limited measurement properties were removed. The
      remaining items (n = 41) were grouped into scales using factor analysis, and then
      refined to form the Multiple Sclerosis Impact Scale (MSIS-29), an instrument
      measuring the physical (20 items) and psychological (nine items) impact of
      multiple sclerosis. Five psychometric properties of the MSIS-29 (data quality,
      scaling assumptions, acceptability, reliability and validity) were examined in a
      separate postal survey of 1250 Multiple Sclerosis Society members. A preliminary
      responsiveness study of the MSIS-29 was undertaken in 55 people admitted for
      rehabilitation and intravenous steroid treatment of relapses. The MSIS-29
      satisfied all psychometric criteria. Data quality was excellent, missing data
      were low (maximum 3.9%), item test-re-test reliability was high (r = 0.65-0.90)
      and scale scores could be generated for >98% of respondents. Item descriptive
      statistics, item convergent and discriminant validity, and factor analysis
      indicated that it was legitimate to generate scores for MSIS-29 scales by summing
      items. MSIS-29 scales showed good variability, small floor and ceiling effects,
      high internal consistency (Cronbach's alpha <or=0.91) and high test-re-test
      reliability (intraclass correlation <or=0.87). Correlations with other measures
      and the analysis of group differences provided evidence that the MSIS-29 measures
      the physical and psychological impact of multiple sclerosis. Effect sizes
      (physical scale = 0.82, psychological scale = 0.66) demonstrated preliminary
      evidence of good responsiveness. These results indicate the MSIS-29 is a
      clinically useful and scientifically sound patient-based outcome measure of the
      impact of multiple sclerosis suitable for clinical trials and epidemiological
      studies.

PMID- 11335699
TI  - Central nervous system disease in patients with macrophagic myofasciitis.
AB  - Macrophagic myofasciitis (MMF), a condition newly recognized in France, is
      manifested by diffuse myalgias and characterized by highly specific
      myopathological alterations which have recently been shown to represent an
      unusually persistent local reaction to intramuscular injections of aluminium
      containing vaccines. Among 92 MMF patients recognized so far, eight of them,
      which included the seven patients reported here, had a symptomatic demyelinating
      CNS disorder. CNS manifestations included hemisensory or sensorimotor symptoms
      (four out of seven), bilateral pyramidal signs (six out of seven), cerebellar
      signs (four out of seven), visual loss (two out of seven), cognitive and
      behavioural disorders (one out of seven) and bladder dysfunction (one out of
      seven). Brain T(2)-weighted MRI showed single (two out of seven) or multiple
      (four out of seven) supratentorial white matter hyperintense signals and corpus
      callosum atrophy (one out of seven). Evoked potentials were abnormal in four out
      of six patients and CSF in four out of seven. According to Poser's criteria for
      multiple sclerosis, the diagnosis was clinically definite (five out of seven) or
      clinically probable multiple sclerosis (two out of seven). Six out of seven
      patients had diffuse myalgias. Deltoid muscle biopsy showed stereotypical
      accumulations of PAS (periodic acid-Schiff)-positive macrophages, sparse CD8+ T
      cells and minimal myofibre damage. Aluminium-containing vaccines had been
      administered 3-78 months (median = 33 months) before muscle biopsy (hepatitis B
      virus: four out of seven, tetanus toxoid: one out of seven, both hepatitis B
      virus and tetanus toxoid: two out of seven). The association between MMF and
      multiple sclerosis-like disorders may give new insights into the controversial
      issues surrounding vaccinations and demyelinating CNS disorders. Deltoid muscle
      biopsy searching for myopathological alterations of MMF should be performed in
      multiple sclerosis patients with diffuse myalgias.

PMID- 11335700
TI  - Mitochondrial DNA transfer RNA gene sequence variations in patients with
      mitochondrial disorders.
AB  - Many different pathogenic mutations in the mitochondrial (mt) transfer RNA (tRNA)
      genes have been reported for patients with mitochondrial encephalomyopathy.
      Although some of them are recurrent, most have only been described once and
      appear to be restricted to one patient or to one family. The incidence of mt tRNA
      gene alterations is not known, even though the frequency of some recurrent
      mutations has been analysed both in patients and in the general population. In
      this study, we describe the results of stepwise screening for sequence variations
      in the mt tRNA genes of 166 patients selected according to several criteria.
      Extensive sequence analysis of the tRNA genes was performed using denaturing
      gradient gel electrophoresis. A total of 31 patients (19%) were found to harbour
      significant levels of a pathogenic mutation, thus confirming the importance of mt
      tRNA mutations in human pathology. Forty-three different sequence variations were
      found, illustrating the great diversity of the mtDNA sequence in humans. The
      functional assessment of all these sequence variations represented a difficult
      task; it was mostly based on indirect data, such as the phylogenetic conservation
      of modified nucleotides and the proportions of variant species in different
      tissues of the index case or in blood of maternal relatives. Direct demonstration
      of a correlation between the proportion of heteroplasmic sequence variations and
      the cytochrome c oxidase defect was performed at the single muscle-fibre level.
      Eleven heteroplasmic sequence variations were found, six of which are new
      mutations. One is a known Caucasian polymorphism but the other 10 are pathogenic.
      Two of them are the well-known pathogenic MELAS (mitochondrial myopathy,
      encephalopathy, lactic acidosis and stroke-like episodes) (A3243G) and MERRF
      (myoclonic epilepsy with ragged-red fibres) (A8344G) point mutations. They were
      found in 23 patients. The eight other mutations were restricted to one patient.
      The pathogenic nature of these mutations was demonstrated directly for five of
      them and hypothesized from indirect arguments for the other three. Thirty-two
      homoplasmic sequence variations were found. Twenty-nine were considered to be
      polymorphisms, even though 15 of these were found for the first time in our
      patients and two others had been reported previously as pathogenic. The
      pathogenic nature of three homoplasmic variants remains questionable.

PMID- 11335701
TI  - Behavioural profiles of children and adolescents after pre- or perinatal
      unilateral brain damage.
AB  - Recent case reports of individuals with early-onset damage to the prefrontal
      cortex have suggested that such early insults could result in severely impaired
      social behaviour in later childhood and adolescence. The investigators speculated
      that the acquisition of complex social conventions and moral rules had been
      impaired. In a large cohort of children, we sought to determine whether early
      focal brain insults might result in clinically significant behavioural or
      emotional problems. This study reports on 39 children with pre- or perinatal
      onset unilateral brain damage (focal lesion) from cerebral infarction or
      intraparenchymal haemorrhage, using the Achenbach Child Behavior Checklist to
      assess the presence or absence of behavioural and emotional difficulties. Two
      thirds of the subjects had left hemisphere (LH) lesions and one-third had right
      hemisphere (RH) lesions. Age range was 4.0-15.4 years at the time of
      questionnaire completion. Their results were compared with those of 54 control
      children. Analyses were conducted on focal lesion versus controls, RH versus LH
      lesion, frontal versus non-frontal lesion, and seizure versus non-seizure groups.
      When the effect of IQ was partialled out, there were no significant differences
      on the nine Behavior Problem scales, the Internalizing-Externalizing dichotomy or
      the Total Problem score for any of the group comparisons. Our subjects showed no
      evidence of clinically significant behavioural or emotional problems, even when
      the frontal lobe was involved. Individuals with more extensive and bilateral
      damage may be at higher risk of significant behavioural and emotional dysfunction
      than were those in our study population. In future studies of brain-behaviour
      relationships in developing children, all potential causes for any observed
      behavioural abnormalities, such as genetic and environmental factors and toxin
      exposure, must be considered before concluding that specific anatomical lesions
      are causally related to specific behavioural outcomes.

PMID- 11335702
TI  - Brain activity during biofeedback relaxation: a functional neuroimaging
      investigation.
AB  - The mechanisms by which cognitive processes influence states of bodily arousal
      are important for understanding the pathogenesis and maintenance of stress
      related morbidity. We used PET to investigate cerebral activity relating to the
      cognitively driven modulation of sympathetic activity. Subjects were trained to
      perform a biofeedback relaxation exercise that reflected electrodermal activity
      and were subsequently scanned performing repetitions of four tasks: biofeedback
      relaxation, relaxation without biofeedback and two corresponding control
      conditions in which the subjects were instructed not to relax. Relaxation was
      associated with significant increases in left anterior cingulate and globus
      pallidus activity, whereas no significant increases in activity were associated
      with biofeedback compared with random feedback. The interaction between
      biofeedback and relaxation, highlighting activity unique to biofeedback
      relaxation, was associated with enhanced anterior cingulate and cerebellar vermal
      activity. These data implicate the anterior cingulate cortex in the intentional
      modulation of bodily arousal and suggest a functional neuroanatomy of how
      cognitive states are integrated with bodily responses. The findings have
      potential implications for a mechanistic account of how therapeutic
      interventions, such as relaxation training in stress-related disorders, mediate
      their effects.

PMID- 11335703
TI  - Sporadic cerebellar ataxia associated with gluten sensitivity.
AB  - A total of 104 patients with sporadic cerebellar ataxia were tested for
      antigliadin and antiendomysium antibodies. Twelve individuals (11.5%) with gluten
      sensitivity underwent duodenal biopsy and extensive clinical,
      electrophysiological, neuropsychological, radiological and laboratory
      investigations including human leucocyte antigen (HLA) typing. Two patients
      showed typical changes of gluten-sensitive enteropathy with crypt hyperplasia and
      mucosal flattening. In five patients, the intraepithelial lymphocyte count was
      elevated. Sporadic ataxia with gluten sensitivity was found to be tightly linked
      to the HLA DQB1*0201 haplotype (70%). Neurological symptoms were not related to
      hypovitaminosis or inflammatory CSF changes. The clinical syndrome was dominated
      by progressive cerebellar ataxia with ataxia of stance and gait (100%),
      dysarthria (100%) and limb ataxia (97%). Oculomotor abnormalities were gaze
      evoked nystagmus (66.7%), spontaneous nystagmus (33.3%), saccade slowing (25%)
      and upward gaze palsy (16.7%). Extracerebellar features also included deep
      sensory loss (58.3%), bladder dysfunction (33.3%) and reduced ankle reflexes
      (33.3%). In accordance with clinical findings, electrophysiological
      investigations revealed prominent axonal neuropathy with reduced amplitudes (50%)
      and abnormal evoked potentials (58.3%). On neuropsychological testing, patients
      presented with moderate verbal memory and executive dysfunction. All patients had
      evidence of cerebellar atrophy on MRI. We conclude that sporadic ataxia may be
      associated with positive antibodies against gliadin. Nevertheless, mucosal
      pathology does not represent an obligatory condition of ataxia with gluten
      sensitivity. The fact that the disease is strongly associated with the same HLA
      haplotypes found in coeliac disease not only demonstrates coeliac disease and
      ataxia with gluten sensitivity to be part of the same disease entity but supports
      the hypothesis of an immunological pathogenesis of cerebellar degeneration.

PMID- 11335704
TI  - The role of the striatum and hippocampus in planning: a PET activation study in
      Parkinson's disease.
AB  - Previous work has identified the prefrontal cortex (PFC) and striatum as
      participating in the planning and selection of movements. We compared the brain
      activation patterns during planning in Parkinson's disease patients and age
      matched controls using H(2)(15)O-PET and the Tower of London (TOL) task. In this
      study, our mildly affected Parkinson's disease group performed as well as the
      control group but showed a different pattern of neuronal activation. In the two
      groups, overlapping areas of the PFC were activated but, whereas the right
      caudate nucleus was activated in the control group, this was not evident in the
      Parkinson's disease patients. This suggests that normal normal frontal lobe
      activation can occur in Parkinson's disease despite abnormal processing within
      the basal ganglia. Moreover, right hippocampus activity was suppressed in the
      controls and enhanced in the Parkinson's disease patients. This could represent a
      shift to the declarative memory system in Parkinson's disease during performance
      of the TOL task, possibly resulting from insufficient working memory capacity
      within the frontostriatal system.

PMID- 11335705
TI  - Elevated cerebrospinal fluid quinolinic acid levels are associated with region
      specific cerebral volume loss in HIV infection.
AB  - Neuronal injury, dendritic loss and brain atrophy are frequent complications of
      infection with human immunodeficiency virus (HIV) type 1. Activated brain
      macrophages and microglia can release quinolinic acid, a neurotoxin and NMDA (N
      methyl-D-aspartate) receptor agonist, which we hypothesize contributes to
      neuronal injury and cerebral volume loss. In the present cross-sectional study of
      94 HIV-1-infected patients, elevated CSF quinolinic acid concentrations
      correlated with worsening brain atrophy, quantified by MRI, in regions vulnerable
      to excitotoxic injury (the striatum and limbic cortex) but not in regions
      relatively resistant to excitotoxicity (the non-limbic cortex, thalamus and white
      matter). Increased CSF quinolinic acid concentrations also correlated with higher
      CSF HIV-1 RNA levels. In support of the specificity of these associations, blood
      levels of quinolinic acid were unrelated to striatal and limbic volumes, and CSF
      levels of beta(2)-microglobulin, a non-specific and non-excitotoxic marker of
      immune activation, were unrelated to regional brain volume loss. These results
      are consistent with the hypothesis that quinolinic acid accumulation in brain
      tissue contributes to atrophy in vulnerable brain regions in HIV infection and
      that virus replication is a significant driver of local quinolinic acid
      biosynthesis.

PMID- 11335706
TI  - Stroke after bone marrow transplantation: frequency, aetiology and outcome.
AB  - Few data exist on the frequency, aetiology and outcome of cerebrovascular
      complications of bone marrow transplantation (BMT). We reviewed all patients
      undergoing BMT at the Fred Hutchinson Cancer Research Center, Seattle, Wash., USA
      (a large referral institution) over 3 years. We reviewed ICD-9 (International
      Classification of Diseases) codes for ischaemic stroke, seizure, intracranial
      haemorrhage and brain infection. Using standardized forms, we paid detailed
      attention to clinical features and demographics, oncological diagnosis,
      conditioning regimens, neurological history, comorbidities, time from BMT to
      ictus, stroke subtype, radiological and pathological features, and outcomes. We
      identified 36 patients with stroke from 1245 patients who had BMT (2.9%) over 3
      years. These patients' median age was 35 (range 5-60, interquartile range 25-45)
      years. The most common causes of stroke were intracranial haemorrhage related to
      thrombocytopenia (38.9%) and infarction or haemorrhage secondary to fungal
      infection (30.6%). Twenty-five patients (69.4%) died from their stroke; none
      survived without disability. Using a logistic regression model, we found that
      neither demographic (e.g. age, gender) nor clinical (e.g. oncological diagnosis,
      type of BMT, time of stroke after BMT) factors predicted outcome. Stroke occurs
      relatively frequently (incidence almost 3%) after BMT, has a relatively high
      frequency of infection-triggered events, has a neurological outcome not easily
      predicted from available data and is often fatal.

PMID- 11335707
TI  - MRI and assessment of treatment in multiple sclerosis.

PMID- 11335709
TI  - Mutation analysis of membrane type-1 matrix metalloproteinase (MT1-MMP). The role
      of the cytoplasmic tail Cys(574), the active site Glu(240), and furin cleavage
      motifs in oligomerization, processing, and self-proteolysis of MT1-MMP expressed
      in breast carcinoma cells.
AB  - Membrane type-1 matrix metalloproteinase (MT1-MMP) is a key enzyme in the
      activation pathway of matrix prometalloproteinase-2 (pro-MMP-2). Both activation
      and autocatalytic maturation of pro-MMP-2 in trans suggest that MT1-MMP should
      exist as oligomers on the cell surface. To better understand the functions of MT1
      MMP, we designed mutants with substitutions in the active site (E240A), the
      cytoplasmic tail (C574A), and the RRXR furin cleavage motifs (R89A, ARAA, and
      R89A/ARAA) of the enzyme. The mutants were expressed in MCF7 breast carcinoma
      cells that are deficient in both MMP-2 and MT1-MMP. Our results supported the
      existence of MT1-MMP oligomers and demonstrated that a disulfide bridge involving
      the Cys(574) of the enzyme's cytoplasmic tail covalently links MT1-MMP monomers
      on the MCF7 cell surface. The presence of MT1-MMP oligomers also was shown for
      the enzyme naturally expressed in HT1080 fibrosarcoma cells. The single (R89A and
      ARAA) and double (R89A/ARAA) furin cleavage site mutants of MT1-MMP were
      processed in MCF7 cells into the mature proteinase capable of activating pro-MMP
      2 and stimulating cell locomotion. This suggested that furin cleavage is not a
      prerequisite for the conversion of pro-MT1-MMP into the functionally active
      enzyme. A hydroxamate class inhibitor (GM6001, or Ilomastat) blocked activation
      of MT1-MMP in MCF7 cells but not in HT1080 cells. This implied that a matrixin
      like proteinase sensitive to hydroxamates could be involved in a furin
      independent, alternative pathway of MT1-MMP activation in breast carcinoma cells.
      The expression of the wild type MT1-MMP enhanced cell invasion and migration,
      indicating a direct involvement of this enzyme in cell locomotion. In contrast,
      both the C574A and E240A mutations render MT1-MMP inefficient in stimulating cell
      migration and invasion. In addition, the C574A mutation negatively affected cell
      adhesion, thereby indicating critical interactions involving the cytosolic part
      of MT1-MMP and the intracellular milieu.

PMID- 11335710
TI  - Phosphoinositide 3-kinase-dependent regulation of interleukin-3-induced
      proliferation: involvement of mitogen-activated protein kinases, SHP2 and Gab2.
AB  - We have demonstrated previously that class I(A) phosphoinositide 3-kinases play a
      major role in regulation of interleukin-3 (IL)-3-dependent proliferation.
      Investigations into the downstream targets involved have identified the MAPK
      cascade as a target. Expression of Deltap85 and incubation with LY294002 both
      inhibited IL-3-induced activation of Mek, Erk1, and Erk2. This was most
      pronounced during the initial phase of Erk activation. The Mek inhibitor,
      PD98059, blocked IL-3-driven proliferation, an effect enhanced by Deltap85
      expression, suggesting that inhibition of Mek and Erks by Deltap85 contributes to
      the decrease in IL-3-induced proliferation in these cells but that additional
      pathways may also be involved. To investigate the mechanism leading to decreased
      activation of Erks, we investigated effects on SHP2 and Gab2, both implicated in
      IL-3 regulation of Erk activation. Expression of Deltap85 led to a reduction in
      SHP2 tyrosine phosphorylation and its ability to interact with Grb2 and Gab2 but
      increased overall tyrosine phosphorylation of Gab2. LY294002 did not perturb SHP2
      interactions, potentially related to differences in the effects of these
      inhibitors on levels of phosphoinositides. These results imply that the
      regulation of Erks by class I(A) phosphoinositide 3-kinase may contribute to IL-3
      driven proliferation and that both SHP2 and Gab2 are possibly involved in this
      regulation.

PMID- 11335711
TI  - Sequential activation of Rac-1, SEK-1/MKK-4, and protein kinase Cdelta is
      required for interleukin-6-induced STAT3 Ser-727 phosphorylation and
      transactivation.
AB  - Activation of signal transducer and activator of transcription 3 (STAT3) by
      interleukin-6 (IL-6) involves phosphorylation of Tyr-705 and Ser-727, both of
      which are critical for STAT3 transactivation. Here, we demonstrate that IL-6
      activates Rac-1 and SEK-1/MKK-4 of the stress-activated protein kinase pathway,
      as well as protein kinase Cdelta (PKCdelta), as indicated by PKCdelta Thr-505
      phosphorylation. However, JNK-1, the end point kinase of the stress-activated
      protein kinase pathway signal transduction cascade, is not activated by IL-6.
      PKCdelta was found to be associated with SEK-1/MKK-4 in unstimulated HepG2 cells
      but rapidly dissociates from SEK-1/MKK-4 upon IL-6 stimulation to become
      associated with STAT3. Inhibition of PKCdelta using rottlerin (6 microm) or by
      overexpression of dominant negative PKCdelta demonstrates that PKCdelta kinase
      activity is required for STAT3 Ser-727 phosphorylation and transactivation but
      not for STAT3 Tyr-705 phosphorylation or nuclear import. PKCdelta signals
      downstream of Rac-1 and SEK-1/MKK-4, because enhanced STAT3 transactivation
      induced by overexpression of constitutive active RacV12 was strongly abrogated by
      rottlerin, whereas IL-6-induced SEK-1/MKK-4 Thr-223 phosphorylation was not
      affected under these conditions. Studying the kinetics of STAT3 and PKCdelta
      phosphorylation in cytoplasmic and nuclear fractions revealed that STAT3 Tyr-705
      phosphorylation and nuclear translocation precedes PKCdelta Thr-505 and STAT3 Ser
      727 phosphorylation. Furthermore, the IL-6-induced PKCdelta Thr-505 and STAT3 Ser
      727 phosphorylation were only observed in nuclear fractions of HepG2 cells. These
      results demonstrate that IL-6-induced STAT3 transactivation involves the
      sequential activation of Rac-1 and SEK-1/MKK-4, which leads to nuclear
      translocation of PKCdelta by release from a SEK-1/MKK-4-containing complex. Our
      results further indicate that PKCdelta-mediated STAT3 Ser-727 phosphorylation is
      mainly a nuclear event.

PMID- 11335712
TI  - Mechanisms of estrogen receptor action in the myocardium. Rapid gene activation
      via the ERK1/2 pathway and serum response elements.
AB  - We have previously shown that the myocardium is a target tissue for estrogen.
      Here, we have identified rapid non-nuclear estrogen effects on the expression of
      the early growth response gene-1 (Egr-1) in cardiomyocytes. Egr-1 mRNA and
      protein were rapidly and strongly induced by estrogen in an estrogen receptor
      dependent manner via the extracellular signal-regulated kinase, ERK1/2. A
      promoter analysis study of a 1.2-kilobase Egr-1 promoter fragment revealed that
      the serum response elements (SREs) but not the estrogen response elements or AP-1
      sites are responsible for Egr-1 induction by estrogen, identifying a novel
      mechanism of estrogen receptor-dependent gene activation in the myocardium. Both
      estrogen receptor-alpha and -beta induced the Egr-1 promoter via the SREs as well
      as an artificial promoter consisting of only five SREs in cardiomyocytes.
      Electrophoretic mobility shift assays showed that a protein complex containing
      serum response factor or an antigenically related protein was recruited to the
      SREs by estrogen treatment of primary cardiomyocytes. The recruitment of the
      protein complex was inhibited by the specific estrogen receptor antagonist ICI
      182,780 as well as the MEK inhibitor PD 98059. Taken together, these results
      identify SREs as important promoter control elements for an estrogen receptor
      dependent mechanism of gene activation in the myocardium.

PMID- 11335713
TI  - Consecutive steps of phosphorylation affect conformation and DNA binding of the
      chironomus high mobility group A protein.
AB  - The high mobility group (HMG) proteins of the AT-hook family (HMGA) lie
      downstream in regulatory networks with protein kinase C, Cdc2 kinase, MAP kinase,
      and casein kinase 2 (CK2) as final effectors. In the cells of the midge
      Chironomus, almost all of the HMGA protein (cHMGA) is phosphorylated by CK2 at
      two adjacent sites. 40% of the protein population is additionally modified by MAP
      kinase. Using spectroscopic and protein footprinting techniques, we analyzed how
      individual and consecutive steps of phosphorylation change the conformation of an
      HMGA protein and affect its contacts with poly(dA-dT).poly(dA-dT) and a fragment
      of the interferon-beta promoter. We demonstrate that phosphorylation of cHMGA by
      CK2 alters its conformation and modulates its DNA binding properties such that a
      subsequent phosphorylation by Cdc2 kinase changes the organization of the protein
      DNA complex. In contrast, consecutive phosphorylation by MAP kinase, which
      results in a dramatic change in cHMGA conformation, has no direct effect on the
      complex. Because the phosphorylation of the HMGA proteins attenuates binding
      affinity and reduces the extent of contacts between the DNA and protein, it is
      likely that this process mirrors the dynamics and diversity of regulatory
      processes in chromatin.

PMID- 11335714
TI  - Role of ceramide in mediating the inhibition of telomerase activity in A549 human
      lung adenocarcinoma cells.
AB  - This study was designed to analyze whether ceramide, a bioeffector of growth
      suppression, plays a role in the regulation of telomerase activity in A549 cells.
      Telomerase activity was inhibited significantly by exogenous C(6)-ceramide, but
      not by the biologically inactive analog dihydro-C(6)-ceramide, in a time- and
      dose-dependent manner, with 85% inhibition produced by 20 microm C(6)-ceramide at
      24 h. Moreover, analysis of phosphatidylserine translocation from the inner to
      the outer plasma membrane by flow cytometry and of poly(ADP-ribose) polymerase
      degradation by Western blotting showed that ceramide treatment (20 microm for 24
      h) had no apoptotic effects. Trypan blue exclusion, [(3)H]thymidine
      incorporation, and cell cycle analyses, coupled with clonogenic cell survival
      assay on soft agar, showed that ceramide treatment with a 20 microm concentration
      at 24 h resulted in the cell cycle arrest of the majority of the cell population
      at G(0)/G(1) with no detectable cell death. These results suggest that the
      inhibition of telomerase by ceramide is not a consequence of cell death but is
      correlated with growth arrest. Next, to determine the role of endogenous ceramide
      in telomerase modulation, A549 cells were transiently transfected with an
      expression vector containing the full-length bacterial sphingomyelinase cDNA (b
      SMase). The overexpression of b-SMase, but not exogenously applied purified b
      SMase enzyme, resulted in significantly decreased telomerase activity compared
      with controls, showing that the increased endogenous ceramide is sufficient for
      telomerase inhibition. Moreover, treatment of A549 cells with daunorubicin at 1
      microm for 6 h resulted in the inhibition of telomerase, which correlated with
      the elevation of endogenous ceramide levels and growth arrest. Finally, stable
      overexpression of human glucosylceramide synthase, which attenuates ceramide
      levels by converting ceramide to glucosylceramide, prevented the inhibitory
      effects of C(6)-ceramide and daunorubicin on telomerase. Therefore, these results
      provide novel data showing for the first time that ceramide is a candidate
      upstream regulator of telomerase.

PMID- 11335715
TI  - Endostatin binds tropomyosin. A potential modulator of the antitumor activity of
      endostatin.
AB  - The mechanism of action of Endostatin, an endogenous inhibitor of angiogenesis
      and tumor growth, remains unknown. We utilized phage-display technology to
      identify polypeptides that mimic the binding domains of proteins with which
      Endostatin interacts. A conformed peptide (E37) was identified that shares an
      epitope with human tropomyosin implicating tropomyosin as an Endostatin-binding
      protein. We show that recombinant human Endostatin binds tropomyosin in vitro and
      to tropomyosin-associated microfilaments in a variety of endothelial cell types.
      The most compelling evidence that tropomyosin modulates the activity of
      Endostatin was demonstrated when E37 blocked greater than 84% of the tumor-growth
      inhibitory activity of Endostatin in the B16-BL6 metastatic melanoma model. We
      conclude that the E37 peptide mimics the Endostatin-binding epitope of
      tropomyosin and blocks the antitumor activity of Endostatin by competing for
      Endostatin binding. We postulate that the Endostatin interaction with tropomyosin
      results in disruption of microfilament integrity leading to inhibition of cell
      motility, induction of apoptosis, and ultimately inhibition of tumor growth.

PMID- 11335716
TI  - Optimal design features of camelized human single-domain antibody libraries.
AB  - We have constructed a human V(H) library based on a camelized V(H) sequence. The
      library was constructed with complete randomization of 19 of the 23 CDR3 residues
      and was panned against two monoclonal antibody targets to generate V(H) sequences
      for determination of the antigen contact residue positions. Furthermore, the
      feasibility and desirability of introducing a disulfide bridge between CDR1 and
      CDR3 was investigated. Sequences derived from the library showed a bias toward
      the use of C-terminal CDR3 residues as antigen contact residues. Mass
      spectrometric analyses indicated that CDR1-CDR3 disulfide formation was
      universal. However, surface plasmon resonance and NMR data showed that the CDR3
      constraint imposed by the disulfide bridge was not always desirable. Very high
      yields of soluble protein products and lack of protein aggregation, as
      demonstrated by the quality of the (1)H-(15)N HSQC spectra, indicated that the
      V(H) sequence for library construction was a good choice. These results should be
      useful in the design of V(H) libraries with optimal features.

PMID- 11335717
TI  - Interaction of the Arabidopsis receptor protein kinase Wak1 with a glycine-rich
      protein, AtGRP-3.
AB  - The Arabidopsis wall-associated receptor kinase, Wak1, is a member of the Wak
      family (Wak1-5) that links the plasma membrane to the extracellular matrix. By
      the yeast two-hybrid screen, we found that a glycine-rich extracellular protein,
      AtGRP-3, binds to the extracellular domain of Wak1. Further in vitro binding
      studies indicated that AtGRP-3 is the only isoform among the six tested AtGRPs
      that specifically interacts with Waks, and the cysteine-rich carboxyl terminus of
      AtGRP-3 is essential for its binding to Wak1. We also show that Wak1 and AtGRP-3
      form a complex with a molecular size of approximately 500 kDa in vivo in
      conjunction with the kinase-associated protein phosphatase, KAPP, that has been
      shown to interact with a number of plant receptor-like kinases. Binding of AtGRP
      3 to Wak1 is shown to be crucial for the integrity of the complex. Wak1 and AtGRP
      3 are both induced by salicylic acid treatment. Moreover, exogenously added AtGRP
      3 up-regulates the expression of Wak1, AtGRP-3, and PR-1 (for pathogenesis
      related) in protoplasts. Taken together, our data suggest that AtGRP-3 regulates
      Wak1 function through binding to the cell wall domain of Wak1 and that the
      interaction of Wak1 with AtGRP-3 occurs in a pathogenesis-related process in
      planta.

PMID- 11335718
TI  - Orphan G protein-coupled receptor, GPR41, induces apoptosis via a p53/Bax pathway
      during ischemic hypoxia and reoxygenation.
AB  - Orphan receptors that couple to G protein without known ligands are considered to
      relate directly to drug discovery. Here, we examine the expression of various
      orphan receptors in H9c2 cells during ischemic hypoxia and reoxygenation. Among
      orphan receptors examined, the level of G protein-coupled receptor 41 (GPR41)
      mRNA increases significantly, with a peak at 2 h after reoxygenation, and
      recovers to the control level by 3 h after reoxygenation. The level of
      glyceraldehyde-3-phosphate dehydrogenase mRNA used as an internal control remains
      almost constant. The levels of c-fos and c-jun mRNA increase significantly with
      ischemic hypoxia and reoxygenation. The transfection of GPR41 into H9c2 cells
      results in a significant decrease in cell number, with DNA fragmentation observed
      by in vitro and in situ assay. The amount of p53 protein increases significantly
      in the nuclei of cells expressing GPR41, accompanying an increase in the
      transcriptional activity of p53. Consistent with the activation of p53, the level
      of bax mRNA is significantly increased, which leads to an increase in Bax
      protein. Furthermore, the expression of a deletion mutant of a GPR41, which lacks
      the G protein binding site and shows an attenuation of intracellular
      phosphorylation signals to H9c2 cells, inhibits cell death and the increase in
      p53 protein within 24 h after reoxygenation. These observations demonstrate that
      GPR41 is a novel receptor that activates p53 leading to apoptosis during
      reoxygenation after ischemic hypoxia in H9c2 cells. We have designated GPR41 as
      the hypoxia-induced apoptosis receptor, HIA-R.

PMID- 11335719
TI  - Serratia ATP-binding cassette protein exporter, Lip, recognizes a protein region
      upstream of the C terminus for specific secretion.
AB  - Serratia marcescens ATP-binding cassette (ABC) exporter, the Lip system, secretes
      lipase (LipA(SM)), metalloproteases, and a cell surface layer protein homologue
      but not a heme acquisition protein, HasA (HasA(SM)). Secretion of HasA(SM) is
      limited to the Has(SM) system. However, HasA proteins from Pseudomonas
      fluorescens (HasA(PF)) and Pseudomonas aeruginosa were exported through the Lip
      and Has(SM) systems. To investigate the specificity in Lip exporter-mediated
      secretion, secretion analysis was performed using chimeras containing the
      HasA(PF) and HasA(SM) sequences. The segment Val-Ala-Leu (designated R1 to R3
      sites), which is present close to the C terminus of HasA(PF) but not HasA(SM),
      was revealed to be involved in the substrate specificity of the Lip exporter.
      Introduction of amino acid substitutions into the R1-R5 region demonstrated that
      R1, R3, R4, and R5 sites require some specific amino acid residues for Lip
      mediated secretion. The amino acid sequence of the region was conserved
      considerably among the proteins secreted by the Lip exporter. On the contrary,
      the region was not related to HasA secretion through the Has(SM) system.
      Interestingly, a typical C-terminal motif, so far regarded as a secretion signal,
      was not necessary for secretion through either the Lip or the Has(SM) exporter.
      In LipA(SM) secretion via the Lip system, the typical C-terminal motif was not
      essential either, but the presence of a sequence similar to Val-Ala-Leu and its
      location from the C terminus greatly affect the secretion level. Secretion
      analyses using hybrid exporters and competitors exhibited that the R1-R5 region
      was recognized by an ABC protein of the Lip exporter, LipB, and that the
      mutations aborting Lip-mediated secretion in the region resulted in a loss of the
      affinity to LipB. Thus, a determinant within the secretory protein for Lip
      mediated secretion was fully defined.

PMID- 11335720
TI  - Prenylated Rab acceptor protein is a receptor for prenylated small GTPases.
AB  - Localization of Ras and Ras-like proteins to the correct subcellular compartment
      is essential for these proteins to mediate their biological effects. Many members
      of the Ras superfamily (Ha-Ras, N-Ras, TC21, and RhoA) are prenylated in the
      cytoplasm and then transit through the endomembrane system on their way to the
      plasma membrane. The proteins that aid in the trafficking of the small GTPases
      have not been well characterized. We report here that prenylated Rab acceptor
      protein (PRA1), which others previously identified as a prenylation-dependent
      receptor for Rab proteins, also interacts with Ha-Ras, RhoA, TC21, and Rap1a. The
      interaction of these small GTPases with PRA1 requires their post-translational
      modification by prenylation. The prenylation-dependent association of PRA1 with
      multiple GTPases is conserved in evolution; the yeast PRA1 protein associates
      with both Ha-Ras and RhoA. Earlier studies reported the presence of PRA1 in the
      Golgi, and we show here that PRA1 co-localizes with Ha-Ras and RhoA in the Golgi
      compartment. We suggest that PRA1 acts as an escort protein for small GTPases by
      binding to the hydrophobic isoprenoid moieties of the small GTPases and
      facilitates their trafficking through the endomembrane system.

PMID- 11335721
TI  - Crystallographic approach to identification of cyclin-dependent kinase 4 (CDK4)
      specific inhibitors by using CDK4 mimic CDK2 protein.
AB  - Genetic alteration of one or more components of the p16(INK4A)-CDK4,6/cyclin D
      retinoblastoma pathway is found in more than half of all human cancers.
      Therefore, CDK4 is an attractive target for the development of a novel anticancer
      agent. However, it is difficult to make CDK4-specific inhibitors that do not
      possess activity for other kinases, especially CDK2, because the CDK family has
      high structural homology. The three-dimensional structure of CDK2, particularly
      that bound with the inhibitor, has provided useful information for the synthesis
      of CDK2-specific inhibitors. The same approach used to make CDK4-specific
      inhibitors was hindered by the failure to obtain a crystal structure of CDK4. To
      overcome this problem, we synthesized a CDK4 mimic CDK2 protein in which the ATP
      binding pocket of CDK2 was replaced with that of CDK4. This CDK4 mimic CDK2 was
      crystallized both in the free and inhibitor-bound form. The structural
      information thus obtained was found to be useful for synthesis of a CDK4-specific
      inhibitor that does not have substantial CDK2 activity. Namely, the data suggest
      that CDK4 has additional space that will accommodate a large substituent such as
      the CDK4 selective inhibitor. Inhibitors designed to bind into this large cavity
      should be selective for CDK4 without having substantial CDK2 activity. This
      design principle was confirmed in the x-ray crystal structure of the CDK4 mimic
      CDK2 with a new CDK4 selective inhibitor bound.

PMID- 11335722
TI  - Rapamycin blocks sexual development in fission yeast through inhibition of the
      cellular function of an FKBP12 homolog.
AB  - FKBP12 is a ubiquitous and a highly conserved prolyl isomerase that binds the
      immunosuppressive drugs FK506 and rapamycin. Members of the FKBP12 family have
      been implicated in many processes that include intracellular protein folding,
      transport, and assembly. In the budding yeast Saccharomyces cerevisiae and in
      human T cells, rapamycin forms a complex with FKBP12 that inhibits cell cycle
      progression by inhibition of the TOR kinases. We reported previously that
      rapamycin does not inhibit the vegetative growth of the fission yeast
      Schizosaccharomyces pombe; however, it specifically inhibits its sexual
      development. Here we show that disruption of the S. pombe FKBP12 homolog,
      fkh1(+), at its chromosomal locus results in a mating-deficient phenotype that is
      highly similar to that obtained by treatment of wild type cells with rapamycin. A
      screen for fkh1 mutants that can confer rapamycin resistance identified five
      amino acids in Fkh1 that are critical for the effect of rapamycin in S. pombe.
      All five amino acids are located in the putative rapamycin binding pocket.
      Together, our findings indicate that Fkh1 has an important role in sexual
      development and serves as the target for rapamycin action in S. pombe.

PMID- 11335723
TI  - Evaluation of the substrate specificity of human mast cell tryptase beta I and
      demonstration of its importance in bacterial infections of the lung.
AB  - Human pulmonary mast cells (MCs) express tryptases alpha and beta I, and both
      granule serine proteases are exocytosed during inflammatory events. Recombinant
      forms of these tryptases were generated for the first time to evaluate their
      substrate specificities at the biochemical level and then to address their
      physiologic roles in pulmonary inflammation. Analysis of a tryptase-specific,
      phage display peptide library revealed that tryptase beta I prefers to cleave
      peptides with 1 or more Pro residues flanked by 2 positively charged residues.
      Although recombinant tryptase beta I was unable to activate cultured cells that
      express different types of protease-activated receptors, the numbers of
      neutrophils increased >100-fold when enzymatically active tryptase beta I was
      instilled into the lungs of mice. In contrast, the numbers of lymphocytes and
      eosinophils in the airspaces did not change significantly. More important, the
      tryptase beta I-treated mice exhibited normal airway responsiveness. Neutrophils
      did not extravasate into the lungs of tryptase alpha-treated mice. Thus, this is
      the first study to demonstrate that the two nearly identical human MC tryptases
      are functionally distinct in vivo. When MC-deficient W/W(v) mice were given
      enzymatically active tryptase beta I or its inactive zymogen before pulmonary
      infection with Klebsiella pneumoniae, tryptase beta I-treated W/W(v) mice had
      fewer viable bacteria in their lungs relative to zymogen-treated W/W(v) mice.
      Because neutrophils are required to combat bacterial infections, human tryptase
      beta I plays a critical role in the antibacterial host defenses of the lung by
      recruiting neutrophils in a manner that does not alter airway reactivity.

PMID- 11335724
TI  - The amino acid residue at sequence position 5 in the conantokin peptides
      partially governs subunit-selective antagonism of recombinant N-methyl-D
      aspartate receptors.
AB  - Whole cell voltage clamp recordings were performed to assess the ability of
      conantokin-G (con-G), conantokin-T (con-T), and a 17-residue truncated form of
      conantokin-R (con-R[1-17]) to inhibit N-methyl-d-aspartate (NMDA)-evoked currents
      in human embryonic kidney 293 cells transiently expressing various combinations
      of NR1a, NR1b, NR2A, and NR2B receptor subunits. Con-T and con-R[1-17] attenuated
      ion currents in cells expressing NR1a/NR2A or NR1a/NR2B. Con-G did not affect
      NMDA-evoked ionic currents in cells expressing NR1a/NR2A, but it showed
      inhibitory activity in cells expressing NR1a/NR2B receptors and the
      triheteromeric combination of NR1a/NR2A/NR2B. An Ala-rich con-G analog, con
      G[Q6G/gamma7K/N8A/gamma10A/gamma14A/K15A/S16A/N17A] (Ala/con-G, where gamma is
      Gla), in which all nonessential amino acids were altered to Ala residues,
      manifested subunit specificity similar to that of con-G, suggesting that the
      replaced residues are not responsible for selectivity in the con-G framework. A
      sarcosine-containing con-T truncation analog, con-T[1-9/G1Src/Q6G], inhibited
      currents in NR1a/NR2A and NR1a/NR2B receptors, eliminating residues 10-21 as
      mediators of the broad subunit selectivity of con-T. In contrast to the null
      effects of con-G and Ala/con-G at a NR1a/NR2A-containing receptor, some
      inhibition ( approximately 40%) of NMDA-evoked currents was effected by these
      peptides in cells expressing NR1b/NR2A. This finding suggests that the presence
      of exon 5 in NR1b plays a role in the activity of the conantokins. Analysis of
      various conantokin analogs demonstrated that Leu(5) of con-G is an important
      determinant of conantokin selectivity. Taken as a whole, these results suggest
      that the important molecular determinants on conantokins responsible for NMDA
      receptor activity and specificity are discretely housed in specific residues of
      these peptides, thus allowing molecular manipulation of the NMDA receptor
      inhibitory properties of the conantokins.

PMID- 11335725
TI  - Tyrosine-phosphorylated plakoglobin is associated with desmogleins but not
      desmoplakin after epidermal growth factor receptor activation.
AB  - Tyrosine phosphorylation of junctional components has been proposed as a
      mechanism for modulating cell-cell adhesion. Although a correlation exists
      between the tyrosine phosphorylation of the adherens junction protein beta
      catenin and loss of classical cadherin-mediated adhesion, the effects of tyrosine
      phosphorylation on the function of the adherens junction and desmosome-associated
      protein plakoglobin is unknown. In the present study, we investigated the effects
      of epidermal growth factor receptor (EGFR) tyrosine kinase activation on the
      subcellular distribution of plakoglobin and its association with its junctional
      binding partners. Long term epidermal growth factor (EGF) treatment of A431 cells
      revealed a modest decrease in the cytoskeleton-associated pool of plakoglobin
      (Pg) and a corresponding increase in the cytosolic pool of Pg. After short term
      EGF treatment, plakoglobin was rapidly phosphorylated, and tyrosine
      phosphorylated Pg was distributed predominantly in a membrane-associated Triton X
      100-soluble pool, along with a co-precipitating high molecular weight tyrosine
      phosphorylated protein identified as desmoglein 2. Analysis of deletion and point
      mutants defined the primary EGFR-dependent targets as one or more of three C
      terminal tyrosine residues. Whereas phosphorylated Pg remained associated with
      the desmoglein tail after both short and long term EGFR activation, no
      phosphorylated Pg was found associated with the N-terminal Pg-binding domain
      (DPNTP) of the intermediate filament-associated protein, desmoplakin. Together
      these results are consistent with the possibility that EGF-dependent tyrosine
      phosphorylation of Pg may modulate cell-cell adhesion by compromising the link
      between desmosomal cadherins and the intermediate filament cytoskeleton.

PMID- 11335726
TI  - The crystallographic structure of the mannitol 2-dehydrogenase NADP+ binary
      complex from Agaricus bisporus.
AB  - Mannitol, an acyclic six-carbon polyol, is one of the most abundant sugar
      alcohols occurring in nature. In the button mushroom, Agaricus bisporus, it is
      synthesized from fructose by the enzyme mannitol 2-dehydrogenase (MtDH; EC )
      using NADPH as a cofactor. Mannitol serves as the main storage carbon (up to 50%
      of the fruit body dry weight) and plays a critical role in growth, fruit body
      development, osmoregulation, and salt tolerance. Furthermore, mannitol
      dehydrogenases are being evaluated for commercial mannitol production as
      alternatives to the less efficient chemical reduction of fructose. Given the
      importance of mannitol metabolism and mannitol dehydrogenases, MtDH was cloned
      into the pET28 expression system and overexpressed in Escherichia coli. Kinetic
      and physicochemical properties of the recombinant enzyme are indistinguishable
      from the natural enzyme. The crystal structure of its binary complex with NADP
      was solved at 1.5-A resolution and refined to an R value of 19.3%. It shows MtDH
      to be a tetramer and a member of the short chain dehydrogenase/reductase family
      of enzymes. The catalytic residues forming the so-called catalytic triad can be
      assigned to Ser(149), Tyr(169), and Lys(173).

PMID- 11335727
TI  - Vascular endothelial cell growth factor activates CRE-binding protein by
      signaling through the KDR receptor tyrosine kinase.
AB  - Vascular endothelial cell growth factor (VEGF) plays a crucial role in the
      development of the cardiovascular system and in promoting angiogenesis associated
      with physiological and pathological processes. Although a great deal is known of
      the cytoplasmic signaling pathways activated by VEGF, much less is known of the
      mechanisms through which VEGF communicates with the nucleus and alters the
      activity of transcription factors. Binding of VEGF to the KDR/Flk1 receptor
      tyrosine kinase induces phosphorylation of the CRE-binding protein (CREB)
      transcription factor on serine 133 and increases CREB DNA binding and
      transactivation. p38 MAPK/MSK-1 and protein kinase C/p90RSK pathways mediate CREB
      phosphorylation. Confocal microscopy shows that VEGF-induced phosphorylation of
      nuclear CREB is blocked by pharmacological inhibition of protein kinase C and p38
      mitogen-activated protein kinase signaling. Thus, KDR/Flk1 uses multiple pathways
      to transmit signals into the nucleus where CREB becomes activated. These results
      suggest that CREB may play a role in alterations of gene expression important to
      angiogenesis.

PMID- 11335728
TI  - A conserved 3'-untranslated element mediates growth regulation of DNA
      methyltransferase 1 and inhibits its transforming activity.
AB  - Ectopic expression of DNA methyltransferase 1 (DNMT1) has been proposed to play
      an important role in cancer. dnmt1 mRNA is undetectable in growth-arrested cells
      but is induced upon entrance into the S phase of the cell cycle, and until now,
      the mechanisms responsible for this regulation were unknown. In this report, we
      demonstrate that the 3'-untranslated region (3'-UTR) of the dnmt1 mRNA can confer
      a growth-dependent regulation on its own message as well as a heterologous beta
      globin mRNA. Our results indicate that a 54-nucleotide highly conserved element
      within the 3'-UTR is necessary and sufficient to mediate this regulation. Cell
      free mRNA decay experiments demonstrate that this element increases mRNA turnover
      rates and does so to a greater extent in the presence of extracts prepared from
      arrested cells. A specific RNA-protein complex is formed with the 3'-UTR only in
      growth-arrested cells, and a UV cross-linking analysis revealed a 40-kDa protein
      (p40), the binding of which is dramatically increased in growth-arrested cells
      and is inversely correlated with dnmt1 mRNA levels as cells are induced into the
      cell cycle. Although ectopic expression of human DNMT1 lacking the 3'-UTR can
      transform NIH-3T3 cells, inclusion of the 3'-UTR prevents transformation. These
      results support the hypothesis that deregulated expression of DNMT1 with the cell
      cycle is important for cellular transformation.

PMID- 11335729
TI  - Conformation of the Drosophila motor protein non-claret disjunctional in solution
      from X-ray and neutron scattering.
AB  - The quaternary structures of monomeric and dimeric Drosophila non-claret
      disjunctional (ncd) constructs were investigated using synchrotron x-ray and
      neutron solution scattering, and their low resolution shapes were restored ab
      initio from the scattering data. The experimental curves were further compared
      with those computed from crystallographic models of one monomeric and three
      available dimeric ncd structures in the microtubule-independent ADP-bound state.
      These comparisons indicate that accounting for the missing parts in the crystal
      structures for all these constructs is indispensable to obtain reasonable fits to
      the scattering patterns. A ncd construct (MC6) lacking the coiled-coil region is
      monomeric in solution, but the calculated scattering from the crystallographic
      monomer yields a poor fit to the data. A tentative configuration of the missing C
      terminal residues in the form of an antiparallel beta-sheet was found that
      significantly improves the fit. The atomic model of a short dimeric ncd construct
      (MC5) without 2-fold symmetry is found to fit the data better than the symmetric
      models. Addition of the C-terminal residues to both head domains gives an
      excellent fit to the x-ray and neutron experimental data, although the
      orientation of the beta-sheet differs from that of the monomer. The solution
      structure of the long ncd construct (MC1) including complete N-terminal coiled
      coil and motor domains is modeled by adding a straight coiled-coil section to the
      model of MC5.

PMID- 11335730
TI  - Domain structure and mutational analysis of T4 polynucleotide kinase.
AB  - T4 polynucleotide kinase (Pnk) is the founding member of a family of 5'-kinase/3'
      phosphatase enzymes that heal broken termini in RNA or DNA by converting 3'
      PO(4)/5'-OH ends into 3'-OH/5'-PO(4) ends, which are then suitable for sealing by
      RNA or DNA ligases. Here we employed site-directed mutagenesis and biochemical
      methods to dissect the domain structure of the homotetrameric T4 Pnk protein and
      to localize essential constituents of the apparently separate active sites for
      the 5'-kinase and 3'-phosphatase activities. We characterized deletion mutants
      Pnk(42-301) and Pnk(1-181), which correspond to domains defined by proteolysis
      with chymotrypsin. Pnk(1-181) is a monomer with no 3'-phosphatase and low
      residual 5'-kinase activity. Pnk(42-301) is a dimer with no 5'-kinase and low
      residual 3'-phosphatase activity. Four classes of missense mutational effects
      were observed. (i) Mutations K15A, S16A, and D35A inactivated the 5'-kinase but
      did not affect the 3'-phosphatase or the tetrameric quaternary structure of T4
      Pnk. 5'-kinase activity was ablated by the conservative mutations K15R, K15Q, and
      D35N; however, kinase activity was restored by the S16T change. (ii) Mutation
      D167A inactivated the 3'-phosphatase without affecting the 5'-kinase or
      tetramerization. (iii) Mutation D85A caused a severe decrement in 5'-kinase
      activity and only a modest effect on the 3'-phosphatase; the nearby N87A mutation
      resulted in a significantly reduced 3'-phosphatase activity and slightly reduced
      5'-kinase activity. D85A and N87A both affected the quaternary structure,
      resulting in a mixed population of tetramer and dimer species. (iv) Alanine
      mutations at 11 other conserved positions had no significant effect on either 5'
      kinase or 3'-phosphatase activity.

PMID- 11335731
TI  - Lack of mitochondrial anionic phospholipids causes an inhibition of translation
      of protein components of the electron transport chain. A yeast genetic model
      system for the study of anionic phospholipid function in mitochondria.
AB  - Reduction of mitochondrial cardiolipin (CL) levels has been postulated to
      compromise directly the function of several essential enzymes and processes of
      the mitochondria. There is limited genetic evidence for the critical roles with
      which CL and its precursor phosphatidylglycerol (PG) have been associated. A null
      allele of the PGS1 gene from Saccharomyces cerevisiae, which encodes the enzyme
      responsible for the synthesis of the CL precursor PG phosphate, was created in a
      yeast strain in which PGS1 expression is exogenously regulated by doxycycline.
      The addition of increasing concentrations of doxycycline to the growth medium
      causes a proportional decrease to undetectable levels of PGS1 transcript, PG
      phosphate synthase activity, and PG plus CL. The doubling time of this strain
      with increasing doxycycline increases to senescence in non-fermentable carbon
      sources or at high temperatures, conditions that do not support growth of the
      pgs1Delta strain. Doxycycline addition also causes mitochondrial abnormalities as
      observed by fluorescence microscopy. Products of four mitochondrial encoded genes
      (COX1, COX2, COX3, and COB) and one nuclear encoded gene (COX4) associated with
      the mitochondrial inner membrane are not present when PGS1 expression is fully
      repressed. No translation of these proteins can be detected in cells lacking the
      PGS1 gene product, although transcription and splicing appear unaffected. Protein
      import of other nuclear encoded proteins remains unaffected. The remaining
      proteins encoded by mitochondrial DNA are expressed and translated normally.
      Thus, the molecular basis for the lack of mitochondrial function in pgs1Delta
      cells is the failure to translate gene products essential to the electron
      transport chain.

PMID- 11335732
TI  - Multicenter, randomized, double-blind clinical trial to evaluate the efficacy and
      safety of a reduced osmolarity oral rehydration salts solution in children with
      acute watery diarrhea.
AB  - OBJECTIVE: To compare the efficacy of a reduced osmolarity oral rehydration salts
      (ORS) solution (75 mmol/L of sodium [Na], 20 mmol/L of potassium [K], 65 mmol/L
      of chloride, 10 mmol/L of citrate, and 75 mmol/L of glucose; osmolarity, 245
      mosm/L) with that of the standard World Health Organization (WHO) ORS solution.
      DESIGN: A multicenter, double-blind, randomized, controlled clinical trial
      conducted in children with acute diarrhea in 5 developing countries to measure
      mean stool output in the 24 hours after randomization, proportion of children who
      required unscheduled intravenous therapy, proportion of children who vomited in
      the first 24 hours, and diarrhea duration after randomization. RESULTS: A total
      of 675 children who ranged in age from 1 to 24 months and who had acute diarrhea
      and dehydration were enrolled in the trial; 341 were randomized to receive
      reduced osmolarity ORS solution, and 334 were randomized to receive the WHO ORS
      solution. The mean (SE) stool output (g/kg) in the first 24 hours (reduced
      osmolarity ORS solution vs WHO ORS solution = 114 [4] vs 125 [5]) and during the
      total study period (reduced osmolarity ORS solution vs WHO ORS solution = 320
      [18] vs 331 [18]) were comparable. The proportion of children who vomited in the
      first 24 hours (reduced osmolarity ORS solution vs WHO ORS solution = 58% vs 62%)
      and the diarrhea duration in the 2 treatment groups, compared by log rank test,
      were similar. The proportion of children who required unscheduled intravenous
      therapy was significantly lower in children who received reduced osmolarity ORS
      solution (10%) as compared with those who received the WHO ORS solution (15%;
      odds ratio = 0.6, 95% confidence interval = 0.4-1.0). There was no significant
      difference in the incidence of hyponatremia (serum Na <130 mmol/L) at 24 hours
      between the 2 treatment groups (11% in reduced osmolarity ORS solution group vs
      9% in the WHO ORS solution group; odds ratio = 1.3; 95% confidence interval = 0.8
      2.2). The frequency of patients with serum Na <125 mmol/L at 24 hours was 13 of
      341 (4%) in children who were treated with reduced osmolarity ORS solution versus
      7 of 334 (2%) in children who received the WHO ORS solution. CONCLUSIONS:
      Treatment with reduced osmolarity ORS solution was associated with a 33%
      reduction in the need for unscheduled intravenous therapy and had no apparent
      effect on stool output and illness duration when compared with treatment with the
      standard WHO ORS solution. Children with acute diarrhea, therefore, may benefit
      from a reduced osmolarity ORS solution. The results of trials that examine the
      efficacy and safety of reduced osmolarity ORS solution in adult patients with
      cholera have to be taken into consideration before consensus on composition of
      oral rehydration formulation can be reached.

PMID- 11335733
TI  - A randomized, placebo-controlled trial of antimicrobial treatment for children
      with clinically diagnosed acute sinusitis.
AB  - OBJECTIVE: Although antimicrobial treatment for children with acute sinusitis is
      used commonly, it is unclear whether it offers significant clinical benefit. The
      purpose of this study was to evaluate the effectiveness of antimicrobial
      treatments for acute sinusitis as they are used in community pediatric practice.
      METHODS: We conducted a randomized, placebo-controlled trial in 3 community
      pediatric practices in St Louis, Missouri. A total of 188 patients who were
      between the ages of 1 and 18 years and who had had 10 to 28 days of persistent
      sinus symptoms and a clinical diagnosis of acute sinusitis were randomized to
      receive 14 days of amoxicillin (40 mg/kg/d in 3 daily doses), amoxicillin
      clavulanate (amoxicillin 45 mg/kg/d in 2 daily doses), or placebo. Change in
      sinus symptoms was assessed both by a quantitative symptom score (the S5 score)
      and subjectively by the parent. Secondary outcomes included adverse effects of
      treatment and recurrence or relapse of sinus symptoms. Outcomes were assessed by
      telephone interviews over a 2-month period. RESULTS: Of the 161 patients who were
      included in the analysis, 58 received amoxicillin, 48 received amoxicillin
      clavulanate, and 55 received placebo. Day 14 improvement rates were 79%, 81%, and
      79%, respectively. There were no differences in the 14-day change in S5 score
      among treatment groups. The rates of adverse events (amoxicillin, 19%;
      amoxicillin-clavulanate, 11%; placebo, 10%), relapse (amoxicillin, 12%;
      amoxicillin-clavulanate, 13%; placebo, 13%), and recurrence (amoxicillin, 9%;
      amoxicillin-clavulanate, 13%; placebo, 13%) of sinus symptoms were similar among
      treatment groups. CONCLUSION: Neither amoxicillin nor amoxicillin-clavulanate
      offered any clinical benefit compared with placebo for children with clinically
      diagnosed acute sinusitis.

PMID- 11335734
TI  - A randomized trial of alternative two- and three-dose hepatitis B vaccination
      regimens in adolescents: antibody responses, safety, and immunologic memory.
AB  - OBJECTIVES: Hoping to increase hepatitis B (HB) vaccination of adolescents, we
      did the following: 1) studied if modified regimens of the recombinant HB vaccine,
      Recombivax HB (2 or 3 doses of 5 or 10 microg given over 4 or 6 months), induce
      protective anti-hepatitis B surface antibody [anti-HBsAb] levels (>/=10 mIU/mL)
      comparable to the recommended regimen (5 microg at 0 and 1, and 6 months); 2)
      measured early antibody response after a single dose; and 3) assessed immunologic
      memory after 2- and 3-dose regimens. DESIGN: One thousand twenty-six adolescents
      were randomized to 1 of 5 treatment groups (10 microg at 0 and 4 or 0 and 6
      months; 5 microg at 0 and 6 or 0, 2, and 4 or 0, 1, and 6 months) in an open
      trial. Anti-HBsAb was measured in all participants just before and 1 month after
      the last dose, and at several other times in a subset of vaccinees. Anti-HBsAb
      response to a booster dose 2 years later was examined to assess immunologic
      memory in participants vaccinated with 5 microg at 0 and 6 or 0, 1, and 6 months.
      RESULTS: All regimens induced >/=10 mIU/mL of anti-HBs in >/=95% of vaccinees.
      Geometric mean titers ranged from 674.8 to 3049.4 mIU/mL. Geometric mean titers
      were higher with regimens using the following: 1) 10 versus 5 microg; 2) 3 versus
      2 doses; and 3) vaccination intervals of 6 versus 4 months. After 6 months, 63.8%
      of vaccinees given one 10-microg dose had >/=10 mIU/mL of anti-HBsAb versus 41.6%
      after one 5-microg dose. Participants vaccinated with either two or three 5
      microg doses retained robust immunologic memory. CONCLUSIONS: . The results of
      this study show that a 2-dose regimen of Recombivax HB is as immunogenic and
      induces immunologic memory as effectively as the recommended 3-dose regimen. A
      regimen of two 10-microg doses may be of significant benefit for vaccinees who
      are poorly compliant or deviate from the intended vaccination schedule.

PMID- 11335735
TI  - A population-based study of crashes involving 16- and 17-year-old drivers: the
      potential benefit of graduated driver licensing restrictions.
AB  - OBJECTIVE: To evaluate the potential effectiveness of graduated driver licensing
      programs using population-based linked data for motor vehicle crashes (MVCs) that
      involved teenaged drivers (TDs). METHODS: Utah crash, inpatient hospital
      discharge, and emergency department databases were analyzed and probabilistically
      linked. We computed hospital charges and compared violations, contributing
      factors, seatbelt use, and passengers for TDs (16-17 years old) relative to adult
      drivers (18-59 years old). RESULTS: TDs comprised 5.8% of the study population,
      but were involved in 19.0% of MVCs. TD crashes resulted in $11 million in
      inpatient hospital charges and 158 fatalities. TD crashes were 1.70 times (95%
      confidence interval [CI]: 1.34, 2.04) less likely to result in fatal injury to
      drivers than were crashes that involved adult drivers, but TDs were 2.20 times
      (95% CI: 1.96, 2.47) more likely to receive citations. The following were
      findings of the study: 1) 11% of all TD crashes but 19% of fatal TD crashes
      occurred between 2200 and 0600 hours; 2) TDs used seatbelts less often than did
      adult drivers (79.1% vs 84.4%) and less often with passengers present (81.9% vs
      75.0%; 3) TDs were 1.72 times (95% CI: 1.38, 2.14) more likely to be involved in
      crashes that resulted in seriously or fatally injured occupants when driving with
      passengers than when driving alone. CONCLUSIONS: TDs are overrepresented in MVCs.
      TD crashes have a higher fatality rate at night, and TDs wear seatbelts less
      often than do adult drivers. Passengers affect TD crash characteristics.
      Graduated driver licensing programs that target state-specific characteristics of
      TDs may decrease morbidity and mortality.

PMID- 11335736
TI  - Randomized trial of nasal synchronized intermittent mandatory ventilation
      compared with continuous positive airway pressure after extubation of very low
      birth weight infants.
AB  - OBJECTIVE: To determine whether noninvasive, nasal synchronized intermittent
      mandatory ventilation (nSIMV) improves the likelihood that very low birth weight
      infants will be successfully extubated. METHODS: Infants of <1251-g birth weight
      who were due to be extubated before 6 weeks of age were eligible once they were
      receiving <35% oxygen and were on a ventilator rate of <18 breaths per minute
      (bpm). Extubation was performed following intravenous loading with aminophylline,
      after a successful trial of 12 hours of endotracheal synchronized intermittent
      mandatory ventilation at a rate of 8. Infants were randomized to either nasal
      continuous positive airway pressure (nCPAP) at 6 cm H(2)O or nSIMV after
      extubation. nSIMV was commenced at a rate of 12 bpm with pressure on the
      ventilator set to achieve a delivered pressure of at least 12 cm H(2)O and a peak
      end expiratory pressure of 6 cm H(2)O. Continuous recording for diagnosis of
      apnea was performed for 72 hours after extubation. Objective criteria for failure
      of extubation were as follows: a PaCO(2) >70; FIO(2) >0.7; or severe recurrent
      apnea (>2 apneas requiring intermittent positive-pressure ventilation in 24 hours
      or >6 apneas >20 seconds per day). The study ended after 72 hours postextubation
      or when infants satisfied failure criteria. A sample size of 54 was determined by
      power analysis. RESULTS: Mean birth weight (831 standard deviation [SD]: 193 g)
      and gestation (26.3 SD: 1.8 weeks) did not differ between groups. Mean age at
      extubation was 7.6 (SD: 9.7) days, range 1 to 40 days. The nSIMV group had a
      lower incidence of failed extubation 4/27 compared with the continuous positive
      airway pressure group, 12/27. This was attributable to both a decreased incidence
      of apnea and a decreased incidence of hypercarbia. There was no increase in the
      incidence of abdominal distension or feeding intolerance. DISCUSSION: nSIMV is
      effective in preventing extubation failure in very low birth weight infants in
      the first 72 hours after extubation. Noninvasive ventilation may have other roles
      in the care of the very low birth weight infant.

PMID- 11335737
TI  - Resuscitation with room air instead of 100% oxygen prevents oxidative stress in
      moderately asphyxiated term neonates.
AB  - BACKGROUND: Traditionally, asphyxiated newborn infants have been ventilated using
      100% oxygen. However, a recent multinational trial has shown that the use of room
      air was just as efficient as pure oxygen in securing the survival of severely
      asphyxiated newborn infants. Oxidative stress markers in moderately asphyxiated
      term newborn infants resuscitated with either 100% oxygen or room air have been
      studied for the first time in this work. METHODS: Eligible term neonates with
      perinatal asphyxia were randomly resuscitated with either room air or 100%
      oxygen. The clinical parameters recorded were those of the Apgar score at 1, 5,
      and 10 minutes, the time of onset of the first cry, and the time of onset of the
      sustained pattern of respiration. In addition, reduced and oxidized glutathione
      concentrations and antioxidant enzyme activities (superoxide dismutase, catalase,
      and glutathione peroxidase) were determined in blood from the umbilical artery
      during delivery and in peripheral blood at 72 hours and at 4 weeks' postnatal
      age. RESULTS: Our results show that the room-air resuscitated (RAR) group needed
      significantly less time to first cry than the group resuscitated with 100% oxygen
      (1.2 +/- 0.6 minutes vs 1.7 +/- 0.5). Moreover, the RAR group needed less time
      undergoing ventilation to achieve a sustained respiratory pattern than the group
      resuscitated with pure oxygen (4.6 +/- 0.7 vs 7.5 +/- 1.8 minutes). The reduced
      to-oxidized-glutathione ratio, which is an accurate index of oxidative stress, of
      the RAR group (53 +/- 9) at 28 days of postnatal life showed no differences with
      the control nonasphyxiated group (50 +/- 12). However, the reduced-to-oxidized
      glutathione ratio of the 100% oxygen-resuscitated group (OxR) (15 +/- 5) was
      significantly lower and revealed protracted oxidative stress. Furthermore, the
      activities of superoxide dismutase and catalase in erythrocytes were 69% and 78%
      higher, respectively, in the OxR group than in the control group at 28 days of
      postnatal life. Thus, this shows that these antioxidant enzymes, although higher
      than in controls, could not cope with the ongoing generation of free radicals in
      the OxR group. However, there were no differences in antioxidant enzyme
      activities between the RAR group and the control group at this stage.
      CONCLUSIONS: There are no apparent clinical disadvantages in using room air for
      ventilation of asphyxiated neonates rather than 100% oxygen. Furthermore, RAR
      infants recover more quickly as assessed by Apgar scores, time to the first cry,
      and the sustained pattern of respiration. In addition, neonates resuscitated with
      100% oxygen exhibit biochemical findings reflecting prolonged oxidative stress
      present even after 4 weeks of postnatal life, which do not appear in the RAR
      group. Thus, the current accepted recommendations for using 100% oxygen in the
      resuscitation of asphyxiated newborn infants should be further discussed and
      investigated.

PMID- 11335738
TI  - Effect of a statewide neonatal resuscitation training program on Apgar scores
      among high-risk neonates in Illinois.
AB  - OBJECTIVE: The national Neonatal Resuscitation Program (NRP), started in 1987,
      provided training to hospital delivery room personnel to standardize knowledge
      and skills to reduce neonatal morbidity and mortality and increase successful
      resuscitation during the first few critical minutes after birth. The Apgar score
      continues to be used as the best established index of immediate postnatal health.
      The purpose of this study was to evaluate the impact of the NRP instruction in
      Illinois hospitals by examining Apgar scores among high-risk infants who are
      likely to benefit from the NRP. METHODS: A retrospective 3-time period cohort
      design was used (before the introduction of the NRP, 1985-1988; transition when
      NRP training occurred, 1989-1990; and after NRP training was completed at least
      once for some delivery room personnel in each Illinois hospital, 1991-1995).
      Illinois computerized birth certificate files on a selected group of 636 429 high
      risk neonates provided information on Apgar scores and maternal characteristics.
      The American Academy of Pediatrics provided instructor lists to determine when
      NRP training started and when it was fully implemented in Illinois. Illinois
      Department of Public Health provided data to categorize hospitals into levels
      based on type and intensity of neonatal services (Level I, II, II+, III). High
      risk neonates were defined as meeting 1 of the following criteria: maternal age
      <20 years old or >35 years old, birth weight <2500 g or >4000 g, presence of a
      maternal medical risk factor, and no prenatal care or prenatal care started after
      the first trimester. Several exclusion criteria were applied including the
      following: birth records with missing data, multiple birth or congenital anomaly,
      and hospital information that indicate no birth deliveries in 1 of the 11 study
      years or delivery outside of a hospital. One-minute and 5-minute Apgar scores
      were divided into categories for analysis (0-3, 4-6, 7-10). No change or a
      decrease in a low (0-6) 1-minute Apgar when compared with the 5-minute Apgar was
      a primary measure to evaluate effect of NRP resuscitation. Variables examined
      included the following: race/ethnicity, maternal age, level of education,
      presence of maternal medical risk factor, trimester started prenatal care,
      complications of labor and delivery, and a low birth weight. Analysis consisted
      of chi(2) tests, relative risk calculations, and logistic regression to reveal
      independent associations with no change in low 1-minute Apgar score or continued
      low (0-6) 5-minute Apgar. RESULTS: A total of 636 429 high-risk birth records was
      selected for detailed analyses out of 2 077 533 births in Illinois between 1985
      and 1995 for 193 hospitals. The number of active NRP instructors in Illinois
      changed dramatically during the study period; for example, 1 to 6 between 1987
      and 1988 to 1096 to 1242 between 1991 and 1995. The percentage of neonates
      reported to have low (<7) 1-minute Apgar score decreased in 1991 to 1995 overall
      and for each of 4 hospital levels. Overall and by hospital level, there was a
      statistically significant lower proportion of high-risk newborns who showed a
      decrease or no change in their 5-minute Apgar scores after the NRP instruction.
      After adjusting for several maternal characteristics, logistic regression
      analysis revealed that high-risk newborns with a low 1-minute Apgar were more
      likely to increase their 5-minute Apgar after the NRP instruction in 1991 to
      1995. Additional analyses indicated that very low birth weight and low birth
      weight newborns benefited the most from NRP instruction. CONCLUSION: Although
      previous research has shown that the NRP instruction improves knowledge and skill
      among health care personnel in the delivery room, both short-term and long-term,
      there has been little evidence to demonstrate NRP impact on infant morbidity.
      Several strategies were used in this study to control for bias and to adjust for
      secular trends in decreased infant morbidity during the study period. This study
      demonstrated sufficient support for the hypothesis that a significant improvement
      occurred among neonates in their Apgar score after the NRP instruction in
      Illinois. Empirical support is provided for the clinical effectiveness of NRP
      instruction.

PMID- 11335739
TI  - Screening guidelines for retinopathy of prematurity: the need for revision in
      extremely low birth weight infants.
AB  - OBJECTIVE: To determine whether significant retinopathy of prematurity (ROP) can
      be detected before 31 to 33 weeks' postmenstrual age (PMA) in extremely low birth
      weight (ELBW) infants. METHODS: Medical records of all ELBW infants (<1000 g at
      birth) admitted to our regional perinatal center between April 1995 and January
      1999 were reviewed retrospectively. Screening examinations for ROP were routinely
      performed at 4 to 6 weeks' chronological age (CA) from birth and followed at
      least every other week. Data were collected for infants who developed ROP. We
      determined the PMA at which the first screening eye examination demonstrated
      prethreshold disease and the subsequent examination that showed threshold disease
      (if it occurred). The percentages of infants who developed prethreshold ROP
      diagnosed at </=31 weeks' PMA and of those who progressed to threshold ROP before
      34 weeks' PMA were determined. RESULTS: All 258 ELBW infants were screened for
      ROP. Seventy-eight infants (30%) were diagnosed with prethreshold ROP. Twenty
      seven of these infants (35%) progressed to threshold ROP. Ten infants who
      progressed to threshold ROP were <34 weeks' PMA at the time of this diagnosis. Of
      these 10 infants, 3 were diagnosed at 31 weeks' PMA, 4 at 32 weeks', and 3 at 33
      weeks'. CONCLUSION: More than 80% of ELBW infants who developed prethreshold
      disease in this cohort were </=33 weeks' PMA. The joint statement screening
      option of independently using 31 to 33 weeks' PMA for the first eye examination
      would have led to a diagnosis of threshold ROP on first examination in as many as
      13% (10/78) of our patients. Early identification of prethreshold ROP is
      important for providing timely intervention in this rapidly progressive disease.
      Therefore, ELBW infants should receive initial ROP screening using the CA
      guideline of 4 to 6 weeks rather than the 31- to 33-week postconceptional age
      guideline.

PMID- 11335740
TI  - Effect of caffeine on oxygen consumption and metabolic rate in very low birth
      weight infants with idiopathic apnea.
AB  - OBJECTIVE: Methylxanthines are among the most commonly prescribed drugs in
      neonatal intensive care. This study evaluates the effect of caffeine on oxygen
      consumption and metabolic rate in premature infants with idiopathic apnea.
      METHODS: Eighteen preterm infants at gestational ages from 28 to 33 weeks and
      birth weights of 890 to 1680 g were enrolled in the study. Nine preterm infants
      received caffeine therapy, and 9 served as a control group. Oxygen consumption
      and energy expenditure were examined before, during, and after caffeine
      treatment. RESULTS: Oxygen consumption increased significantly from 7.0 +/- 0.9
      before caffeine to 8.8 +/- 0.7 mL/kg/min after 48 hours of caffeine therapy, and
      energy expenditure increased from 2.1 +/- 0.3 to 3.0 +/- 0.2 kcal/kg/hour. During
      the observation period of 4 weeks of caffeine treatment, oxygen consumption
      increased significantly in the caffeine group compared with the control patients.
      In the caffeine group, a lower environmental temperature was sufficient to
      maintain a normal body temperature. With similar caloric intake in both groups
      during the study period, daily weight gain in the control group was significantly
      higher (21 +/- 4 vs 42 +/- 2 g/d). None of the other parameters recorded changed
      during caffeine therapy. CONCLUSION: Long-term administration of caffeine in
      preterm infants is associated with an increase in oxygen consumption and with a
      reduction of weight gain. This may have implications for clinical practice as
      nutritional regimens need to be adjusted during this therapy.

PMID- 11335741
TI  - Bilirubin and serial auditory brainstem responses in premature infants.
AB  - OBJECTIVES: To determine the usefulness of the bilirubin-albumin (B:A) molar
      ratio (MR) and unbound bilirubin (UB) as compared with serum total bilirubin (TB)
      in predicting bilirubin encephalopathy as assessed by auditory brainstem
      responses (ABR) in infants of 28 to 32 weeks' gestational age. STUDY DESIGN:
      During a 2-year period, serial ABRs were obtained on 143 infants of 28 to 32
      weeks' gestational age during the first postnatal week. Waveforms were
      categorized on the basis of response replicability and the presence of waves III
      and V. Wave V latencies were also serially analyzed when measurable for
      individual infants. Maturation of the ABR was defined as abnormal when the
      waveform category worsened and/or latency increased during the study interval.
      Serum albumin was analyzed at 48 to 72 hours of age in all patients. Serum TB was
      analyzed as clinically indicated. Aliquots of the same samples were also analyzed
      for UB in a subset of infants. RESULTS: The mean peak TB concentration (10.1 +/-
      1.7 mg/dL) for the 71 infants with normal ABR maturation was not significantly
      different from the mean peak TB (10.2 +/- 2.1 mg/dL) in the 24-hour period
      preceding the ABR's first showing abnormal maturation in the other 55 infants.
      However, in infants with UB analyzed, the mean peak UB (0.62 +/- 0.20 vs 0.40 +/-
      0.15 microg/dL) was significantly higher in the infants with abnormal maturation
      (n = 25) than in infants with normal maturation (n = 20). The B:A MR results were
      equivocal. In the entire study population, there was no difference in B:A MR
      between infants with normal versus abnormal ABR maturation. However, in the
      subset of infants in whom UB was measured, although TB was not different, there
      was a significant difference in B:A MR. Based on receiver-operating
      characteristic curves, a UB level of 0.5 microg/dL was the best discriminator
      with a sensitivity of 70% and a specificity of 75%. The proportion of infants who
      had UB >0.5 microg/dL and UB </=0.5 microg/dL and who had abnormal ABR,
      maturation was 0.81 and 0.33, respectively, with a significant difference in the
      incidence of transient bilirubin encephalopathy among these 2 groups. The
      relative risk of abnormal ABR maturation with UB >0.5 microg/dL compared with UB
      </=0.05 microg/dL was 2.45 (95% confidence interval: 1.33-4.49). CONCLUSIONS: UB
      is a more sensitive predictor than either serum bilirubin or B:A MR of abnormal
      ABR maturation, and hence transient bilirubin encephalopathy in premature
      newborns with hyperbilirubinemia.

PMID- 11335742
TI  - Impact of the change in polio vaccination schedule on immunization coverage
      rates: a study in two large health maintenance organizations.
AB  - OBJECTIVE: In January 1997, one of the most significant changes to United States
      vaccine policy occurred when polio immunization guidelines changed to recommend a
      schedule containing inactivated polio vaccine (IPV). There were concerns that
      parent or physician reluctance to accept IPV into the routine childhood
      immunization schedule would lead to lowered coverage. We determined whether
      adoption of an IPV schedule had a negative impact on immunization coverage.
      DESIGN: A cohort study of 2 large health maintenance organizations (HMOs), Group
      Health Cooperative and Kaiser Permanente Northern California, was conducted. For
      analysis at 12 months of age, children who were born between October 1, 1996, and
      December 31, 1997, and were commercially insured and covered by Medicaid were
      continuously enrolled; for analysis at 24 months of age, children who were born
      between October 1, 1996, and June 30, 1997, and were commercially insured and
      covered by Medicaid were continuously enrolled. The 3 measures of immunization
      status at 12 and 24 months of age were up-to-date status, cumulative time spent
      up-to-date, and the number of missed opportunity visits. RESULTS: At both HMOs,
      children who received IPV were as likely to be up to date at 12 months as were
      children who received oral poliovirus vaccine (OPV), whereas at Group Health,
      children who received IPV were slightly more likely to be up to date at 24 months
      (relative risk: 1.12; 95% confidence interval [CI]: 1.05, 1.19). These findings
      were consistent for children who were covered by Medicaid. At Kaiser Permanente,
      children who received IPV spent ~3 fewer days up to date in the first year of
      life, but this difference did not persist at 2 years of age. At Group Health,
      children who received IPV were no different from those who received OPV in terms
      of days spent up to date by 1 or 2 years of age. At Group Health, children who
      received IPV were less likely to have a missed opportunity by 12 months old (odds
      ratio [OR] 0.46; 95% CI: 0.31, 0.70), but this finding did not persist at 24
      months of age. At Kaiser Permanente, children who received IPV were more likely
      to have a missed opportunity by 12 months (OR 2.06; 95% CI: 1.84, 2.30), and 24
      months of age (OR 1.50; 95% CI: 1.36, 1.67). CONCLUSIONS: The changeover from an
      all-OPV schedule to one containing IPV had little if any negative impact on
      vaccine coverage. Use of IPV was associated with a small increase in the
      likelihood of being up to date at 2 years of age at one of the HMOs and
      conversely was associated with a small increase in the likelihood of having a
      missed-opportunity visit in the other HMO.polio, poliomyelitis, vaccination,
      immunization coverage.

PMID- 11335743
TI  - Continuation of the decline in prevalence of anemia in low-income infants and
      children in five states.
AB  - OBJECTIVE: To examine whether there is a continuation of the decline in
      prevalence of anemia among low-income infants and children 6.0 to 59.9 months old
      from the early 1980s to the mid-1990s. STUDY DESIGN: Cross-sectional trend
      analysis of data from the Centers for Disease Control and Prevention's Pediatric
      Nutrition Surveillance System from the 5 states (Colorado, New Mexico, Oklahoma,
      Utah, and Vermont) that have been using the same laboratory method for anemia
      screening since 1984 or earlier. RESULTS: The overall prevalence of anemia
      decreased substantially in each state from the early 1980s to the mid-1990s as
      follows: Colorado by 52%; New Mexico by 75%; Oklahoma by 67%; Utah by 57%; and
      Vermont by 48%. In each state, the prevalence of anemia declined for children of
      different age groups, birth weights, genders, type of pediatric care visit
      (screening or follow-up), and most race/ethnic groups. CONCLUSIONS: The decline
      in the prevalence of anemia initially observed in the 1980s continued well into
      the 1990s. This decline is likely attributable to better iron nutrition related
      to greater usage of iron-fortified products and possibly better iron
      bioavailability in some of the food products.

PMID- 11335744
TI  - Growth of preterm infants fed nutrient-enriched or term formula after hospital
      discharge.
AB  - OBJECTIVE: At hospital discharge, preterm infants may have low body stores of
      nutrients, deficient bone mineralization, and an accumulated energy deficit. This
      double-blind, randomized study evaluated the growth of premature infants with
      birth weights <1800 g who were fed a 22 kcal/fl oz nutrient-enriched
      postdischarge formula (PDF) or a 20 kcal/fl oz term-infant formula (TF) from
      hospital discharge to 12 months' corrected age (CA). METHODS: Infants were
      randomized to PDF or TF a few days before hospital discharge with stratification
      by gender and birth weight (<1250 g or >/=1250 g). The formulas were fed to 12
      months' CA. Growth was evaluated using analysis of variance controlling for site,
      feeding, gender, and birth weight group. Interaction effects were also assessed.
      Secondary analyses included a repeated measures analysis and growth modeling.
      RESULTS: One hundred twenty-five infants were randomized; 74 completed to 6
      months' CA and 53 to 12 months' CA. PDF-fed infants weighed more than TF-fed
      infants at 1 and 2 months' CA, gained more weight from study day 1 to 1 and 2
      months' CA, and were longer at 3 months' CA. There were significant interactions
      between feeding and birth weight group-among infants with birth weights <1250 g,
      those fed PDF weighed more at 6 months' CA, were longer at 6 months' CA, had
      larger head circumferences at term 1, 3, 6, and 12 months' CA, and gained more in
      head circumference from study day 1 to term and to 1 month CA. The repeated
      measures and growth modeling analyses confirmed the analysis of variance results.
      The PDF formula seemed to be of particular benefit for the growth of male
      infants. Infants fed the PDF consumed less formula and had higher protein intakes
      at several time points. Energy intakes, however, were not different. CONCLUSIONS:
      Growth was improved in preterm infants fed a nutrient-enriched postdischarge
      formula after hospital discharge to 12 months' CA. Beneficial effects were most
      evident among infants with birth weights <1250 g, particularly for head
      circumference measurements.

PMID- 11335746
TI  - Thermal stress in sudden infant death: Is there an ambiguity with the rebreathing
      hypothesis?
AB  - OBJECTIVE: To assess the role of thermal stress in the cause of sudden infant
      death syndrome (SIDS), and to compare risk factors with those of rebreathing.
      METHODOLOGY: Analysis of publications concerning the epidemiology and physiology
      of thermal stress in SIDS. RESULTS: A strong association between thermal
      regulation and ventilatory control was found, specifically for prolonged apnea.
      Infections, excessive room heat and insulation, and prone sleeping produce
      significantly increased odds ratios for SIDS. Although some of the risk factors
      for rebreathing could be explained by the effects of thermal stress, several
      factors for thermal stress could not reasonably be explained by the rebreathing
      hypothesis. CONCLUSIONS: Although the risk of thermal stress is widely accepted
      abroad, it has received relatively little attention in the United States. The
      incidence of SIDS in the United States can likely be further reduced by educating
      the public against the dangers of overheating, as an integral part of the back-to
      sleep campaign.

PMID- 11335745
TI  - Serotonin transporter gene variation is a risk factor for sudden infant death
      syndrome in the Japanese population.
AB  - OBJECTIVE: Serotonin (5-HT) in the nervous system is a major factor in
      facilitation of the brain center for respiration. Variations in the promoter
      region of the 5-HT transporter (5-HTT) gene have been shown to potentially
      regulate 5-HT activity in the brain. Therefore, we aimed to identify the
      possibility that specific allele variants of the 5-HTT gene can be found as a
      genetic background for sudden infant death syndrome (SIDS). METHODS:
      Polymorphisms in the 5' regulatory region of the 5-HTT gene were determined in
      genomic DNA obtained from 27 SIDS victims and 115 age-matched health control
      participants. RESULTS: There were significant differences in genotype
      distribution and allele frequency of the 5-HTT promoter gene between SIDS victims
      and age-matched control participants. The L and XL alleles were more frequently
      found in SIDS victims than in age-matched control participants. CONCLUSION:
      Efficiency in the transportation of 5-HTT with the L allele is known to be higher
      than that with the S allele. The excitatory function by 5-HT is considered to be
      lower in the respiratory center of individuals with the L allele compared with
      those with S allele. The XL allele variant has shown another novel biological
      risk factor for SIDS.

PMID- 11335747
TI  - Genetic counseling and neonatal screening for cystic fibrosis: an assessment of
      the communication process.
AB  - OBJECTIVE: To assess the effectiveness of communication between health care
      providers (physicians, nurses, genetic counselors) in Wisconsin and parents of
      children identified as heterozygote carriers for cystic fibrosis (CF) in the
      routine Wisconsin Newborn Screening Program that was implemented using
      trypsinogen/DNA testing. METHODS: Routine CF neonatal screening, implemented in
      July 1994, involved a statewide system that recommended but did not mandate
      follow-up sweat tests at 1 of the Wisconsin's 2 certified CF centers. The
      Wisconsin Division of Health sent requests to participate to the parents of 483
      infants identified as CF carriers between July 1994 and December 1997. Of the 483
      parents, 183 agreed to participate and were asked to complete a questionnaire
      assessing their CF newborn screening experiences and their knowledge of CF
      genetics and any changes they made in their reproductive behavior as a result of
      this knowledge. Follow-up telephone interviews by a genetic counselor were
      attempted within 1 year for those completing the questionnaire. RESULTS: Within 4
      months after the mailing, 138 of 183 (75%) parents completed the questionnaire.
      Subsequently, 123 of the 138 responders (89%) were contacted and interviewed by
      telephone. We learned that 67.6% of parents recalled receiving genetic
      counseling, but 32.4% of parents apparently did not participate in a risk
      communication session. When asked, "Who performed the genetic counseling?"
      parents indicated that their communication was with physicians in 8% of cases,
      nurses in 12.4%, and certified genetic counselors in 32.8% of cases; 17.5% of
      parents did not recall who performed the genetic counseling and 29.2% of parents
      indicated they did not receive genetic counseling. Based on the 138 responses, it
      was found that 88.3% of parents understood that their child was a carrier for CF,
      but 15.4% of parents were unsure whether being a carrier could cause illness. In
      addition, 12.4% of parents were unsure whether at least 1 of them (parents) was a
      carrier of the CF gene. Only 57% of parents knew there was a 1 in 4 chance that
      their child could have a child with CF if he or she reproduced with another
      carrier of the CF gene. Statistically significant differences were noted when
      comparing the frequency of correct responses between parents who received genetic
      counseling and parents who had not. The frequency of accurate responses did not
      depend on which health care professional provided the genetic counseling.
      Comparing responses of parents who were seen at a certified CF center with
      parents seen at other community hospitals and clinics revealed significant
      differences in the frequency of correct responses, with the former group showing
      a higher percentage of correct responses. Telephone interviews revealed that
      11.4% of parents were unaware that their child was a carrier for CF and that
      54.5% wished they had more information made available to them at the time of the
      initial positive newborn screen result, before the definitive sweat test. Also,
      13.8% of parents recommended that community physicians be better informed of the
      details and implications of positive screening results for CF. CONCLUSION:
      Genetic counseling is imperative for the success of newborn screening for CF and
      other congenital diseases. With the completion of the Human Genome Project, more
      molecular screening for childhood disease is bound to enter the clinical arena.
      Based on our findings, efforts must be made to ensure that newborn screening
      programs have the means and the methods to communicate newborn screening results
      effectively to families. In addition, both the general public and community
      health providers must be better informed of the implications of all newborn
      screening results. Additional research is needed to determine whether there are
      communication styles and approaches that are better suited to counseling parents
      regarding newborn screening results.

PMID- 11335748
TI  - Impact of inhaled antiinflammatory therapy on hospitalization and emergency
      department visits for children with asthma.
AB  - OBJECTIVE: Although the efficacy of inhaled antiinflammatory therapy in improving
      symptoms and lung function in childhood asthma has been shown in clinical trials,
      the effectiveness of these medications in real-world practice settings in
      reducing acute health care use has not been well-evaluated. This study examined
      the effect of inhaled antiinflammatory therapy on hospitalizations and emergency
      department (ED) visits by children for asthma. DESIGN: Defined population cohort
      study over 1 year. Setting. Three managed care organizations (MCOs) in Seattle,
      Boston, and Chicago participating in the Pediatric Asthma Care-Patient Outcome
      Research and Treatment II trial. Participants. All 11 195 children, between 3 to
      15 years old, with a diagnosis of asthma who were enrolled in the 3 MCOs between
      July 1996 and June 1997. OUTCOME MEASURES: We identified children with 1 or more
      asthma diagnoses using automated encounter data. Medication dispensings were
      identified from automated pharmacy data. Multivariate logistic regression
      analysis was used to calculate effects of inhaled antiinflammatory therapy on the
      adjusted relative risk (RR) for hospitalization and ED visits for asthma.
      RESULTS: Over 12 months, 217 (1.9%) of children had an asthma hospitalization,
      and 757 (6.8%) had an ED visit. After adjustment for age, gender, MCO, and
      reliever dispensing, compared with children who did not receive controllers, the
      adjusted RRs for an ED visit were: children with any (>/=1) dispensing of
      cromolyn, 0.4 (95% confidence interval [CI]: 0.3, 0.5); any inhaled
      corticosteroid (ICS), 0.5 (95% CI: 0.4, 0.6); any cromolyn or ICS combined (any
      controller), 0.4 (95% CI: 0.3, 0.5). For hospitalization, the adjusted RR for
      cromolyn was 0.6 (95% CI: 0.4, 0.9), for ICS 0.4 (95% CI: 0.3, 0.7), and for any
      controller 0.4 (95% CI: 0.3, 0.6). A significant protective effect for both
      events was seen among children with 1 to 5 and with >5 antiinflammatory
      dispensings. When the analysis was stratified by frequency of reliever
      dispensing, there was a significant protective effect for controllers on ED
      visits for children with 1 to 5 and with >5 reliever dispensings and on the risk
      of hospitalization for children with >5 reliever dispensings. CONCLUSIONS:
      Inhaled antiinflammatory therapy is associated with a significant protective
      effect on the risk for hospitalization and ED visits in children with asthma.
      Cromolyn and ICSs were associated with similar effects on risks.asthma drug
      therapy, inhaled antiinflammatory agents, health maintenance organizations,
      hospitalization, emergency department.

PMID- 11335749
TI  - Neonatal thyroxine supplementation in very preterm children: developmental
      outcome evaluated at early school age.
AB  - OBJECTIVE: Transient hypothyroxinemia in very premature infants is associated
      with developmental problems. A randomized, placebo-controlled trial of thyroxine
      (T(4)) supplementation was conducted in a group of 200 infants <30 weeks'
      gestation. T(4) supplementation improved mental outcome at 2 years old in
      children of 25/26 weeks' gestation only. The effect of T(4) supplementation
      beyond 2 years of age is unknown. We present the effects of neonatal T(4)
      supplementation on outcome at early school age. METHODS: Standardized
      measurements were used to assess cognitive, behavioral, and motor outcome, as
      well as a qualitative assessment of neurologic functioning. Survivors of the T(4)
      trial were assessed at the age of 5.7 years. RESULTS: Ninety-nine percent of the
      157 survivors participated. Outcome on all domains was comparable between the
      T(4) group and placebo group. In children <27 weeks' gestation, a 10 IQ point
      difference was found in favor of the T(4) group, whereas in children of 29 weeks'
      gestation, a difference of 15 IQ points was found in favor of the placebo group.
      Teachers' reports showed less behavioral problems in the T(4)-treated children of
      25/26 weeks' gestation, but more behavioral problems in the T(4)-treated children
      of 27 weeks' gestation. Differences in motor outcome and neurologic outcome were
      in favor of the T(4)-treated children <29 weeks' gestation, but not of the T(4)
      treated children of 29 weeks' gestation. CONCLUSIONS: We found benefits of T(4)
      supplementation for children <29 weeks' gestation, and especially in children of
      25/26 weeks' gestation. However, in children of 29 weeks' gestation T(4)
      supplementation is associated with more developmental problems.

PMID- 11335750
TI  - Comparison of findings on cranial ultrasound and magnetic resonance imaging in
      preterm infants.
AB  - OBJECTIVE: To compare findings on hard copies of cranial ultrasound (US) and
      magnetic resonance imaging (MRI) obtained between birth and term in a group of
      preterm infants. PARTICIPANTS AND METHODS: Infants born at or below a gestational
      age of 30 weeks who underwent cranial US scan and MRI on the same day were
      eligible for this study. Infants underwent, whenever possible, 3 scans between
      birth and term. We calculated the predictive probability (PP) of US findings as a
      predictor of findings on MRI. RESULTS: Sixty-two paired MRI and US studies were
      performed between birth and term in 32 infants born at a median gestational age
      of 27 (range: 23-30) weeks and a median birth weight of 918 (530-1710) grams. US
      predicted some MRI findings accurately: germinal layer hemorrhage (GLH) on US had
      a PP of 0.8 with a 95% confidence interval of (0.70-0.90) for the presence of GLH
      on MRI, intraventricular hemorrhage (IVH) on US had a PP of 0.85 (0.76-0.94) for
      the presence of IVH on MRI, and severe white matter (WM) echogenicity on US had a
      PP of 0.96 (0.92-1.0) for the presence of WM hemorrhagic parenchymal infarction
      on MRI. Other MRI changes were less well-predicted: mild or no WM echogenicity on
      US had a PP of 0.54 (0.41-0.66) for the presence of normal WM signal intensity on
      MRI, and moderate or severe WM echogenicity on US had a PP of 0.54 (0.42-0.66)
      for the presence of small petechial WM hemorrhage and/or diffuse excessive high
      signal intensity (DEHSI) in the WM on T2-weighted images on MRI. However,
      mild/moderate or severe WM echogenicity on US scans performed at >/=7 days after
      birth had a PP of 0.72 (0.58-0.87) for the presence of WM hemorrhage and/or DEHSI
      on MRI. There were no cases of cystic periventricular leukomalacia. CONCLUSION:
      US accurately predicted the presence of GLH, IVH, and hemorrhagic parenchymal
      infarction on MRI. However, its ability to predict the presence of DEHSI and
      small petechial hemorrhages in the WM on T2 weighted images is not as good, but
      improves on scans performed at >/=7 days after birth. In addition, normal WM
      echogenicity on US is not a good predictor of normal WM signal intensity on MRI.

PMID- 11335751
TI  - Type and timing of mothers' victimization: effects on mothers and children.
AB  - OBJECTIVES: There is mounting concern about how mothers' own victimization
      experiences affect their children. This study examines the effects of mothers'
      victimization on their own mental health and parenting and on their children's
      behavior, development, and health. The effects of both timing and type of
      victimization are assessed. A related objective was to determine if there was a
      cumulative risk effect produced by victimization during both childhood and
      adulthood, or both physical and sexual. SETTING: Urban families in an eastern
      state and urban and rural families in a southern state. PARTICIPANTS: A total of
      419 mothers and their children 6 to 7 years old were identified from 2 sites. The
      eastern sample was recruited in the first 2 years of life from 3 pediatric
      clinics: 1 for children at high risk for human immunodeficiency virus disease, 1
      for children with failure to thrive, and a third providing pediatric primary
      care. The southern sample was derived from a cohort of children at risk for
      adverse health or developmental outcomes, plus a systematic sampling of controls,
      recruited from area hospitals. At age 4, a random sample of children from the
      original cohort who had been maltreated along with a matched comparison group of
      nonmaltreated children were selected. RESULTS: In general, mothers victimized
      during both childhood and adulthood had poorer outcomes than mothers victimized
      during either childhood/adolescence or adulthood who in turn had worse outcomes
      than mothers with no history of victimization. This manifested as more maternal
      depressive symptoms, harsher parenting, and more externalizing and internalizing
      behavior problems in their children. There were no significant differences in
      maternal functioning or child outcomes between those abused in childhood and
      those abused in adulthood. These findings were similar for type of victimization.
      Mothers' depression and harsh parenting were directly associated with their
      children's internalizing and externalizing behavior problems. CONCLUSIONS:
      Maternal victimization appears to be a highly prevalent problem in high-risk
      samples and is associated with harmful implications for mental health and
      parenting, as well as for the offspring. Pediatricians need to consider past and
      current victimization of mothers. Routine screening for these problems, followed
      by appropriate evaluation and intervention may reduce maternal depression,
      improve parenting, and reduce the incidence of behavior problems in children.

PMID- 11335752
TI  - Impact of the Oregon Health Plan on children with special health care needs.
AB  - OBJECTIVE: Although an increasing number of Medicaid children are enrolled in
      Medicaid managed care plans, little is known about how children with special
      health care needs fare under such programs. Of particular concern is the ability
      of such children to navigate a managed care system and gain access to specialty
      and other services. This study compares the managed care experiences of children
      with and without special care needs in the Oregon Health Plan. METHODOLOGY:
      Telephone surveys were conducted with a sample of parents of children enrolled in
      the Oregon Health Plan. Three groups of children were sampled: Supplemental
      Security Income (SSI) children with disabilities, children with asthma, and
      children without special health care needs. Descriptive and multivariate analyses
      were conducted to determine the impact of Medicaid managed care on access and
      satisfaction. RESULTS: Children with disabilities in managed care plans did not
      experience any more difficulty accessing needed specialty care than did those
      without special health care needs. Children with asthma, however, reported higher
      levels of unmet need. There were no differences in access between children with
      disabilities enrolled in managed care and those children with disabilities
      remaining in fee-for-service. CONCLUSIONS: Unlike SSI children with disabilities,
      children who were not SSI-eligible but had asthma seemed to have difficulty
      obtaining some services. These children were not eligible for the same consumer
      protections afforded SSI children by Oregon. If states want to enroll all
      children with special health care needs into managed care programs, they must
      develop mechanisms for identifying such children and ensuring that they receive
      medically necessary services.

PMID- 11335753
TI  - Evaluation of growth and hormonal status in patients referred to the
      International Fanconi Anemia Registry.
AB  - OBJECTIVES: 1) To determine the extent of short stature in patients with Fanconi
      anemia (FA); 2) to determine the extent and nature of endocrinopathy in FA; 3) to
      assess the impact on height of any endocrinopathies in these patients; and 4) to
      study the correlation, if any, between height, endocrinopathy, and FA
      complementation group. STUDY DESIGN: Fifty-four patients with FA, 30 males and 24
      females from 47 unrelated families, were prospectively evaluated in a Pediatric
      Clinical Research Center. The patients ranged in age from 0.1-31.9 years, with
      the mean age at assessment 8.6 years. RESULTS: Endocrine abnormalities were found
      in 44 of the 54 FA patients tested (81%), including short stature, growth hormone
      (GH) insufficiency, hypothyroidism, glucose intolerance, hyperinsulinism, and/or
      overt diabetes mellitus. Twenty-one of 48 (44%) participants had a subnormal
      response to GH stimulation; 19 of 53 (36%) had overt or compensated
      hypothyroidism, while 8 of 40 participants had reduced thyroid-hormone binding.
      Two patients were diabetic at the time of study; impaired glucose tolerance was
      found in 8 of 40 patients (25%), but most surprisingly, hyperinsulinemia was
      present in 28 of 39 (72%) participants tested. Significantly, spontaneous
      overnight GH secretion was abnormal in all patients tested (n = 13). In addition,
      participants demonstrated a tendency toward primary hypothyroidism with serum
      tetraiodothyronine levels at the lower range of normal, while also having
      thyrotropin (thyroid-stimulating hormone) levels at the high end of normal.
      Sixteen patients were assigned to FA complementation group A, (FA-A), 12 to FA-C,
      and 5 to FA-G; 10 of the 12 participants in FA-C were homozygous for a mutation
      in the intron-4 donor splice site of the FANCC gene. Patients in groups FA-A and
      FA-G were relatively taller than the group as a whole (but still below the mean
      for the general population), whereas those in FA-C had a significantly reduced
      height for age. GH response to stimulation testing was most consistently normal
      in participants from FA-G, but this did not reach statistical significance. The
      tendency toward hypothyroidism was more pronounced in participants belonging to
      complementation groups FA-C and FA-G, whereas insulin resistance was most evident
      in patients in FA-G, and least evident in those in FA-C. Short stature was a very
      common finding among the patients with a mean height >2 standard deviations below
      the reference mean (standard deviation score: -2.35 +/- 0.28). Patients with
      subnormal GH response and those with overt or compensated hypothyroidism were
      shorter than the group with no endocrinopathies. The heights of those
      participants with glucose or insulin abnormalities were less severely affected
      than those of normoglycemic, normoinsulinemic participants, although all were
      significantly below the normal mean. The mean height standard deviation score of
      patients with entirely normal endocrine function was also >2 standard deviations
      below the normal mean, demonstrating that short stature is an inherent feature of
      FA. CONCLUSION: Endocrinopathies are a common feature of FA, primarily
      manifesting as glucose/insulin abnormalities, GH insufficiency, and
      hypothyroidism. Although short stature is a well-recognized feature of FA, 23
      patients (43%) were within 2 standard deviations, and 5 of these (9% of the
      total) were actually above the mean for height for the general population. Those
      patients with endocrine dysfunction are more likely to have short stature. These
      data indicate that short stature is an integral feature of FA, but that
      superimposed endocrinopathies further impact on growth. The demonstration of
      abnormal endogenous GH secretion may demonstrate an underlying hypothalamic
      pituitary dysfunction that results in poor growth.

PMID- 11335755
TI  - Celiac disease: the past, the present, the future.

PMID- 11335754
TI  - Impact of the Joint Statement by the American Academy of Pediatrics/US Public
      Health Service on thimerosal in vaccines on hospital infant hepatitis B
      vaccination practices.
AB  - OBJECTIVE: To determine the impact of the American Academy of Pediatrics/US
      Public Health Service (AAP/USPHS) joint statement on thimerosal in vaccines on
      hospital infant hepatitis B vaccination policies in Wisconsin. METHODS: The nurse
      managers of hospital newborn nurseries (n = 110) were surveyed by mail.
      Nonresponders were resurveyed. Twelve hospitals no longer provided obstetric
      services. Of the remaining 98 hospitals, 84 (86%) responded to the initial
      mailing and 14 (14%) responded to the second mailing. The number of hospitals
      that offered hepatitis B vaccine to infants before July 1999 was compared with
      that in March 2000. The number of hospitals that had policies in place to
      vaccinate infants whose mothers' hepatitis B surface antigen status (HBsAg) was
      positive or unknown during the thimerosal alert (July 1999 through November 1999)
      was compared with that in March 2000. RESULTS: Before July 1999, 81% of the
      hospitals representing 84% of reported Wisconsin births routinely offered
      hepatitis B vaccine to all infants. By March 2000, 50% of hospitals, representing
      43% of births, had resumed routine infant hepatitis B vaccination. Physician
      decision to use a combination Haemophilus influenzae type b hepatitis B vaccine
      was the most frequently given reason for not reinstituting infant hepatitis B
      vaccination. During the thimerosal alert, 23% of hospitals did not have policies
      to vaccinate infants whose mothers were HBsAg-positive and 51% did not have
      policies to vaccinate infants whose mothers' HBsAg status was unknown. By March
      2000, 6% of hospitals still did not have policies to vaccinate infants whose
      mothers were HBsAg-positive and 24% did not have policies to vaccinate infants
      whose mothers' HBsAg status was unknown. CONCLUSION: The AAP/USPHS joint
      statement on thimerosal in vaccines has resulted in a 38% decrease in the number
      of hospitals routinely offering infants hepatitis B vaccine. Although thimerosal
      free hepatitis B vaccine is now available, some hospitals still do not have
      appropriate policies in place for vaccinating infants whose mothers' HBsAg status
      is positive or unknown. In the future, policymakers should include anticipated
      consequences that may result from changes in immunization policy in their
      recommendations.

PMID- 11335756
TI  - Adolescent hepatitis B immunization: making it simpler.

PMID- 11335757
TI  - Guidelines for preparedness of emergency departments that care for children: a
      call to action.

PMID- 11335758
TI  - Bacteremic infection with Pediococcus: vancomycin-resistant opportunist.
AB  - Pediococci are recently recognized Gram-positive human pathogens, resistant to
      vancomycin and generally susceptible to penicillin. Infection in adults has been
      seen in patients with chronic underlying conditions as well as those with
      previous abdominal surgery. Two previous infants with congenital gastrointestinal
      malformations requiring surgical correction have been reported with sepsis
      attributable to Pediococcus sp. We report a third infant born with gastroschisis
      who developed Pediococcus bacteremia and meningitis 3 months after surgery, and
      speculate regarding the role of probiotics in the pathogenesis of this infection.

PMID- 11335759
TI  - Care of children in the emergency department: guidelines for preparedness.
AB  - Children requiring emergency care have unique and special needs. This is
      especially so for those with serious and life-threatening emergencies. There are
      a variety of components of the emergency care system that provide emergency care
      to children that are not limited to children. With regard to hospitals, most
      children are brought to community hospital emergency departments (EDs) by virtue
      of their availability rather than to facilities designed and operated solely for
      children. Emergency medical services (EMS) agencies, similarly, provide the bulk
      of out-of-hospital emergency care to children. It is imperative that all hospital
      EDs and EMS agencies have the appropriate equipment, staff, and policies to
      provide high quality care for children. This statement provides guidelines for
      necessary resources to ensure that children receive quality emergency care and to
      facilitate, after stabilization, timely transfer to a facility with specialized
      pediatric services when appropriate. It is important to realize that some
      hospitals and local EMS systems will have difficulty in meeting these guidelines,
      and others will develop more comprehensive guidelines based on local resources.
      It is hoped, however, that hospital ED staff and administrators and local EMS
      systems administrators will seek to meet these guidelines to best ensure that
      their facilities or systems provide the resources necessary for the care of
      children. This statement has been reviewed by and is supported in concept by the
      Ambulatory Pediatric Association, American Association of Poison Control Centers,
      American College of Surgeons, American Hospital Association, American Medical
      Association, American Pediatric Surgical Association, American Trauma Society,
      Brain Injury Association Inc, Emergency Nurses Association, Joint Commission on
      Accreditation of Healthcare Organizations, National Association of Children's
      Hospitals and Related Institutions, National Association of EMS Physicians,
      National Association of EMTs, National Association of School Nurses, National
      Association of State EMS Directors, National Committee for Quality Assurance, and
      Society for Academic Emergency Medicine.

PMID- 11335760
TI  - American Academy of Pediatrics: Risk of injury from baseball and softball in
      children.
AB  - This statement updates the 1994 American Academy of Pediatrics policy statement
      on baseball and softball injuries in children. Current studies on acute, overuse,
      and catastrophic injuries are reviewed with emphasis on the causes and mechanisms
      of injury. This information serves as a basis for recommending safe training
      practices and the appropriate use of protective equipment.

PMID- 11335761
TI  - American Academy of Pediatrics: Financing graduate medical education to meet
      pediatric workforce needs.
AB  - This statement reviews the current system of funding for graduate medical
      education (GME) in the United States and evaluates the potential of alternative
      GME funding mechanisms, including a portable authorization system, to meet future
      pediatric workforce needs. It addresses key issues relating to the financing of
      GME: Medicare direct medical education (DME) and indirect medical education
      adjustment (IMEA) payments, an all-payer GME trust fund, and a market mechanism
      to distribute GME funds for both core pediatric and pediatric subspecialty
      education. In a concluding series of recommendations, the statement calls for
      changes to the current system of GME funding to ensure the production of a
      pediatrician workforce that will be able to meet the future needs of infants,
      children, adolescents, and young adults.

PMID- 11335762
TI  - American Academy of Pediatrics: The continued importance of Supplemental Security
      Income (SSI) for children and adolescents with disabilities.
AB  - In 1996, as part of the Personal Responsibility and Work Opportunity
      Reconciliation (Welfare Reform) Act, Congress redefined the Supplemental Security
      Income (SSI) definition of disability for children and removed the individual
      functional assessment (IFA) step from the disability determination process. As a
      result, an estimated 100 000 SSI child beneficiaries have lost or will lose their
      SSI benefits. The publicity associated with this Congressionally mandated change
      might also have reduced the number of families applying for SSI benefits on
      behalf of their children because of a widely held belief that the eligibility
      criteria for disability benefits are now so restrictive that almost no children
      are determined to be eligible. The purpose of this statement is to provide
      updated information about the SSI Program's disability and financial eligibility
      criteria and disability determination process. This statement also discusses how
      pediatricians can help to ensure that all eligible children receive the SSI
      monies and associated benefits to which they are entitled.

PMID- 11335763
TI  - American Academy of Pediatrics: Tobacco's toll: implications for the
      pediatrician.
AB  - The disease of tobacco addiction, which is pervasive in the United States, begins
      in childhood and adolescence. Twenty-five percent of the population regularly
      uses tobacco, despite evidence that such use is the leading preventable cause of
      death in the United States. Tobacco use reportedly kills 2.5 times as many people
      each year as alcohol and drug abuse combined. According to 1998 data from the
      World Health Organization, there were 1.1 billion smokers worldwide and 10 000
      tobacco-related deaths per day. Furthermore, in the United States, 43% of
      children aged 2 to 11 years are exposed to environmental tobacco smoke, which has
      been implicated in sudden infant death syndrome, low birth weight, asthma, middle
      ear disease, pneumonia, cough, and upper respiratory infection. Pediatricians
      play a crucial role in reducing both tobacco use (by children, adolescents, and
      their parents) and exposure to tobacco smoke and should rank this among their
      highest health prevention priorities.

PMID- 11335764
TI  - American Academy of Pediatrics: Health care for children and adolescents in the
      juvenile correctional care system.
AB  - Over the past decade, there has been a dramatic increase in the population of
      juvenile offenders in the United States. Juveniles detained or confined in
      correctional care facilities have been shown to have numerous health problems.
      Such conditions may have existed before incarceration; may be closely associated
      with legal problems; may have resulted from parental neglect, mental health
      disorders, or physical, drug, or sexual abuse; or may develop within the
      institutional environment. Delinquent youths are often disenfranchised from
      traditional health care services in the community. For these adolescents, health
      care provided through correctional services may be their major source of health
      services. Pediatricians and correctional health care systems have an opportunity
      and responsibility to help improve the health of this underserved and vulnerable
      group of adolescents.

PMID- 11335765
TI  - Commercialism in classrooms.
AB  - Opinions expressed in commentaries are those of the authors and not necessarily
      those of the American Academy of Pediatrics or its Committees. Commentaries are
      not peer-reviewed.

PMID- 11335766
TI  - Nutritional rickets in Georgia.
AB  - Opinions expressed in commentaries are those of the authors and not necessarily
      those of the American Academy of Pediatrics or its Committees. Commentaries are
      not peer-reviewed.

PMID- 11335767
TI  - Severe nutritional deficiencies in toddlers resulting from health food milk
      alternatives.
AB  - It is widely appreciated that health food beverages are not appropriate for
      infants. Because of continued growth, children beyond infancy remain susceptible
      to nutritional disorders. We report on 2 cases of severe nutritional deficiency
      caused by consumption of health food beverages. In both cases, the parents were
      well-educated, appeared conscientious, and their children received regular
      medical care. Diagnoses were delayed by a low index of suspicion. In addition,
      nutritional deficiencies are uncommon in the United States and as a result, US
      physicians may be unfamiliar with their clinical features. Case 1, a 22-month-old
      male child, was admitted with severe kwashiorkor. He was breastfed until 13
      months of age. Because of a history of chronic eczema and perceived milk
      intolerance, he was started on a rice beverage after weaning. On average, he
      consumed 1.5 L of this drink daily. Intake of solid foods was very poor. As this
      rice beverage, which was fallaciously referred to as rice milk, is extremely low
      in protein content, the resulting daily protein intake of 0.3 g/kg/day was only
      25% of the recommended dietary allowance. In contrast, caloric intake was 72% of
      the recommended energy intake, so the dietary protein to energy ratio was very
      low. A photograph of the patient after admission illustrates the typical features
      of kwashiorkor: generalized edema, hyperpigmented and hypopigmented skin lesions,
      abdominal distention, irritability, and thin, sparse hair. Because of fluid
      retention, the weight was on the 10th percentile and he had a rotund sugar baby
      appearance. Laboratory evaluation was remarkable for a serum albumin of 1.0 g/dL
      (10 g/L), urea nitrogen <0.5 mg/dL (<0.2 mmol/L), and a normocytic anemia with
      marked anisocytosis. Evaluation for other causes of hypoalbuminemia was negative.
      Therapy for kwashiorkor was instituted, including gradual refeeding, initially
      via a nasogastric tube because of severe anorexia. Supplements of potassium,
      phosphorus, multivitamins, zinc, and folic acid were provided. The patient
      responded dramatically to refeeding with a rising serum albumin and total
      resolution of the edema within 3 weeks. At follow-up 1 year later he continued to
      do well on a regular diet supplemented with a milk-based pediatric nutritional
      supplement. The mortality of kwashiorkor remains high, because of complications
      such as infection (kwashiorkor impairs cellular immune defenses) and electrolyte
      imbalances with ongoing diarrhea. Children in industrialized countries have
      developed kwashiorkor resulting from the use of a nondairy creamer as a milk
      alternative, but we were unable to find previous reports of kwashiorkor caused by
      a health food milk alternative. We suspect that cases have been overlooked. Case
      2, a 17-month-old black male, was diagnosed with rickets. He was full-term at
      birth and was breastfed until 10 months of age, when he was weaned to a soy
      health food beverage, which was not fortified with vitamin D or calcium. Intake
      of solid foods was good, but included no animal products. Total daily caloric
      intake was 114% of the recommended dietary allowance. Dietary vitamin D intake
      was essentially absent because of the lack of vitamin D-fortified milk. The
      patient lived in a sunny, warm climate, but because of parental career demands,
      he had limited sun exposure. His dark complexion further reduced ultraviolet
      light-induced endogenous skin synthesis of vitamin D. The patient grew and
      developed normally until after his 9-month check-up, when he had an almost
      complete growth arrest of both height and weight. The parents reported regression
      in gross motor milestones. On admission the patient was unable to crawl or roll
      over. He could maintain a sitting position precariously when so placed.
      Conversely, his language, fine motor-adaptive, and personal-social skills were
      well-preserved. Generalized hypotonia, weakness, and decreased muscle bulk were
      present. Clinical features of rickets present on examination included: frontal
      bossing, an obvious rachitic rosary (photographed), genu varus, flaring of the
      wrists, and lumbar kyphoscoliosis. The serum alkaline phosphatase was markedly
      elevated (1879 U/L), phosphorus was low (1.7 mg/dL), and calcium was low normal
      (8.9 mg/dL). The 25-hydroxy-vitamin D level was low (7.7 pg/mL) and the
      parathyroid hormone level was markedly elevated (114 pg/mL). The published
      radiographs are diagnostic of advanced rickets, showing diffuse osteopenia,
      frayed metaphyses, widened epiphyseal plates, and a pathologic fracture of the
      ulna. The patient was treated with ergocalciferol and calcium supplements. The
      published growth chart demonstrates the dramatic response to therapy. Gross motor
      milestones were fully regained within 6 months. The prominent neuromuscular
      manifestations shown by this patient serve as a reminder that rickets should be
      considered in the differential diagnosis of motor delay. (ABSTRACT TRUNCATED)

PMID- 11335768
TI  - Recurrent Mycobacterium avium osteomyelitis associated with a novel dominant
      interferon gamma receptor mutation.
AB  - Mycobacterium avium causes infections in immunocompromised individuals. Recurrent
      infection with this organism has been associated with a deletion at the 818
      residue of the interferon-gamma receptor (IFN-gammaR). This mutation produces a
      truncated receptor without an intracytoplasmic tail, resulting in diminished
      signaling. We describe a substitution at the 832 residue of the IFN-gammaR
      causing a similar truncated receptor in a 7-year-old girl with recurrent M avium
      osteomyelitis.

PMID- 11335769
TI  - High levels of interferon gamma in the plasma of children with complete
      interferon gamma receptor deficiency.
AB  - We have found that children with complete interferon gamma (IFNgamma) receptor
      deficiency, unlike patients with other genetic defects predisposing them to
      mycobacterial diseases, have very high levels of IFNgamma in their plasma. This
      unexpected observation provides a simple and accurate diagnostic method for
      complete IFNgamma receptor deficiency in children with clinical disease caused by
      bacille Calmette-Guerin vaccines or environmental nontuberculous mycobacteria.

PMID- 11335770
TI  - Variation in clinician recommendations for multiple injections during adoption of
      inactivated polio vaccine.
AB  - OBJECTIVES: To describe variation in clinician recommendations for multiple
      injections during the adoption of inactivated poliovirus vaccine (IPV) in 2 large
      health maintenance organizations (HMOs), and to test the hypothesis that
      variation in recommendations would be associated with variation in immunization
      coverage rates. DESIGN: Cross-sectional study based on a survey of clinician
      practices 1 year after IPV was recommended and computerized immunization data
      from these clinicians' patients. STUDY SETTINGS: Two large West Coast HMOs:
      Kaiser Permanente in Northern California and Group Health Cooperative of Puget
      Sound. OUTCOME MEASURES: Immunization status of 8-month-olds and 24-month-olds
      cared for by the clinicians during the study. RESULTS: More clinicians at Group
      Health (82%), where a central guideline was issued, had adopted the IPV/oral
      poliovirus vaccine (OPV) sequential schedule than at Kaiser (65%), where no
      central guideline was issued. Clinicians at both HMOs said that if multiple
      injections fell due at a visit and they elected to defer some vaccines, they
      would be most likely to defer the hepatitis B vaccine (HBV) for infants (40%). At
      Kaiser, IPV users were more likely than OPV users to recommend the first HBV at
      birth (64% vs 28%) or if they did not, to defer the third HBV to 8 months or
      later (62% vs 39%). In multivariate analyses, patients whose clinicians used IPV
      were as likely to be fully immunized at 8 months old as those whose clinicians
      used all OPV. At Kaiser, where there was variability in the maximum number of
      injections clinicians recommended at infant visits, providers who routinely
      recommended 3 or 4 injections at a visit had similar immunization coverage rates
      as those who recommended 1 or 2. At both HMOs, clinicians who strongly
      recommended all possible injections at a visit had higher immunization coverage
      rates at 8 months than those who offered parents the choice of deferring some
      vaccines to a subsequent visit (at Kaiser, odds ratio [OR]: 1.2; 95% confidence
      interval [CI]: 1.0-1.5; at Group Health, OR: 1.8; 95% CI: 1.1-2.8). CONCLUSIONS:
      Neither IPV adoption nor the use of multiple injections at infant visits were
      associated with reductions in immunization coverage. However, at the HMO without
      centralized immunization guidelines, IPV adoption was associated with changes in
      the timing of the first and third HBV. Clinical policymakers should continue to
      monitor practice variation as future vaccines are added to the infant
      immunization schedule.

PMID- 11335771
TI  - Effectiveness of a high school smoking cessation program.
AB  - OBJECTIVE: To evaluate the impact of a school-based smoking cessation program
      targeting adolescents interested in quitting. DESIGN: Randomized clinical trial
      over one school year. SETTING: Large public high school. PARTICIPANTS: Students
      interested in quitting smoking. INTERVENTION: Seventy-four students were
      randomized to receive either: 1) a 6-week, 8-session, classroom-based, smoking
      cessation curriculum designed for adolescents (n = 35) or 2) an informational
      pamphlet on how to quit smoking with promise of the classroom curriculum in 3
      months (n = 39). OUTCOME MEASURES: Change in smoking behavior measured by: 1)
      self-reported smoking cessation and exhaled carbon monoxide <6 parts per million
      (smoke-free); 2) self-reported quit attempts; and 3) change in cigarettes per day
      (cpd) at the end of the 6-week curriculum and then 4, 10, and 20 weeks later.
      Saliva cotinine was also measured at these points to validate these outcome
      measures. Analysis. Intention-to-treat. RESULTS: Participants in the classroom
      group attended an average of 4.4 sessions. At the end of the curriculum, the
      classroom group was significantly more likely to be smoke-free (59% vs 17%), to
      have tried to quit smoking (82% vs 54%), and to reduce mean cpd (7.0 vs 1.0).
      Four weeks later, these differences persisted: smoke-free (52% vs 20%), quit
      attempt (85% vs 60%), and reduction in mean cpd (6.6 vs 1.6). Changes in saliva
      cotinine were consistent with reported outcome measures; those who were smoke
      free had a significant reduction in saliva cotinine at the end of the
      intervention, and at 4 weeks. At 10 and 20 weeks after the curriculum, 41% and
      31%, respectively, of the classroom group remained smoke-free. Once participants
      in the pamphlet group underwent the classroom intervention (average attendance of
      2.2 sessions) their cessation rates were similar to the initial group: 31% at the
      end of the curriculum and 27% 10 weeks later. CONCLUSION: A school-based
      curriculum for adolescent smoking cessation is more effective than an
      informational pamphlet alone and reduces cigarette use by adolescents. More
      research is needed to test the reproducibility, sustainability, and
      generalizability of this curriculum to offer more smoking cessation options to
      teenagers.

PMID- 11335772
TI  - Development and evaluation of a method for evaluating pediatric residents'
      knowledge and skill in performing physical examinations of the ankle and knee.
AB  - BACKGROUND: Pediatric residents need the knowledge and physical examination
      skills to evaluate common musculoskeletal injuries. The ankle and the knee are
      the 2 most common sites of musculoskeletal injury in young athletes. Methods for
      evaluating pediatric residents' knowledge and skills in examining the ankle and
      knee are needed. OBJECTIVES: 1) To describe the development of a method for
      evaluating pediatric residents' knowledge and skill in performing physical
      examinations of the ankle and knee, and 2) to report the reliability of this
      method. METHODS: A written test and a Clinical Skills Assessment Examination
      (CSAE) with a rating index were developed by the investigators to evaluate
      pediatric residents' knowledge and skills in examining the ankle and knee. Fifty
      eight pediatric residents completed the written test and examined the ankle and
      knee of one standardized patient at the beginning of a required 1-month
      adolescent medicine rotation. Forty-eight residents repeated the evaluation at
      the end of the month. The investigators rated the residents' performance of the
      CSAE and then assessed interrater reliability using Cronbach's alpha. Test-retest
      correlation was calculated to assess the reliability of the written test.
      RESULTS: Test-retest correlation for the written test was 0.72, establishing its
      reliability. Interrater reliability for rating the CSAE of the ankle and knee was
      0.98 and 0.90, respectively. CONCLUSION: Pediatric residents' knowledge and
      skills in examining the ankle and knee can be reliably evaluated using the
      written test and CSAE described in this article. These could be used to assess
      the effectiveness of current curricula in improving pediatric residents'
      knowledge and skill in evaluating ankle and knee complaints and to assist in the
      design of future curricula. musculoskeletal, evaluation methods, resident
      curriculum.

PMID- 11335773
TI  - Pediatric residents' performance of ankle and knee examinations after an
      educational intervention.
AB  - BACKGROUND: Pediatric residents have the need for additional training in the care
      of common musculoskeletal injuries. OBJECTIVES: To implement and evaluate the
      effects of a teaching intervention on pediatric residents' knowledge and skills
      in performing the physical examination of the ankle and knee. STUDY DESIGN:
      Prospective, intervention, single-sample study design. METHODS: Pediatric
      residents (n = 58) on a 1-month adolescent medicine rotation received a teaching
      intervention after a baseline evaluation of their knowledge and skills. The
      teaching intervention was designed to improve their knowledge about and skills in
      performing physical examinations of the ankle and knee. The intervention included
      watching a videotape, followed by observation of the attending physician
      demonstrating the techniques on a standardized patient, followed by correct
      demonstration of the techniques by the resident. The residents' knowledge and
      skills were assessed at the end of the rotation and 9 months later. Knowledge was
      assessed using a written examination. Skills assessment was performed using a
      Clinical Skills Assessment Examination. RESULTS: At baseline, the residents
      performed 37% of the ankle and 18% of the knee physical examination techniques
      correctly. At 1 and 9 months, the residents' knowledge of ankle and knee
      examinations was greater than at baseline. The residents performed 77% of the
      techniques correctly at 1 month and 67% at 9 months. The residents performed 55%
      of the knee examination techniques correctly at 1 month and 47% at 9 months. The
      teaching intervention was rated highly by the residents. CONCLUSIONS: The
      residents' performance of ankle and knee examinations was suboptimal at baseline
      and improved significantly after the teaching intervention. Observed improvements
      persisted for a mean of 35 weeks. The teaching intervention described in this
      study could meet the need for improved ankle and knee examination skills, the 2
      most common sites of skeletal injury in young athletes. The teaching model is
      novel in that it couples videotape and skills-based teaching methods with
      reliable evaluation methods. This model teaching method could be adapted for use
      in other pediatric residency training programs and other content areas.
      musculoskeletal, physical examination, resident curriculum.

PMID- 11335774
TI  - Hypovitaminosis D in healthy schoolchildren.
AB  - BACKGROUND: Vitamin D is essential for skeletal growth, but there are currently
      no guidelines for vitamin D supplementation after infancy. This study
      investigates vitamin D insufficiency in healthy children. METHODS: Children ages
      10 to 16 years from 3 private schools in Beirut, Lebanon, with differing
      socioeconomic status (SES) were studied: 169 in the spring of 1999 and 177 in the
      following fall; 83 students participated in both study phases. They had a
      physical examination, answered a dietary questionnaire, and blood was drawn for
      calciotropic hormones and indices of bone turnover. RESULTS: Overall, 52% of the
      students were vitamin D-insufficient; the proportion of insufficiency was 65% in
      the winter and 40% at the end of the summer. During both seasons, girls had lower
      vitamin D levels than did boys; those who followed the dress code of covered
      head, arms, and legs had the lowest levels. Students in the mid-SES school had
      lower 25-hydroxyvitamin D (25-OHD) levels than did the ones from the high-SES
      school. After adjusting for confounders, gender, SES, and body mass index
      remained the significant predictors of vitamin D levels in both seasons (R(2) =
      0.53, for spring and 0.28 for fall). There was a significant inverse correlation
      between 25-OHD levels and parathyroid hormone levels that was best fitted by a
      curvilinear model (R(2) = 0.19). CONCLUSION: Even in a sunny country,
      hypovitaminosis D is common in schoolchildren, more so in the winter. Girls,
      especially those with a lower SES, are at particular risk. The inverse changes in
      parathyroid hormone suggest that insufficient vitamin D levels may deleteriously
      affect skeletal metabolism in healthy adolescents. Vitamin D insufficiency may be
      prevalent in many other countries where supplementation of milk with vitamin D is
      not mandatory. Our results call to a reconsideration of vitamin D supplementation
      in high-risk adolescents to further optimize skeletal health. vitamin D
      insufficiency, bone metabolism, nutrition, gender, socioeconomic status.

PMID- 11335775
TI  - Targeted testing of children for tuberculosis: validation of a risk assessment
      questionnaire.
AB  - OBJECTIVE: Given the directive of the American Academy of Pediatrics to test
      children for tuberculosis (TB) only if they are at high risk for the disease, we
      sought to determine how well a risk assessment questionnaire can predict a
      positive tuberculin skin test (TST) result among children seen in a medical
      office setting. METHODS: In a prospective observational study, we identified 31
      926 children who received well-child care in 18 pediatric offices of the Kaiser
      Permanente Northern California Region from August 1996 through November 1998 and
      who were due to receive a routine TST (Mantoux method) as part of universal
      screening. Parents were asked to complete a questionnaire about risk factors for
      TB infection that included demographic information. The TST result at 48 to 72
      hours was compared with questionnaire responses to identify responses that were
      most highly associated with a positive TST result at both the 10-mm and 15-mm
      cutoffs. A concurrent study was conducted to determine whether parents can
      recognize induration. RESULTS: This population was diverse in age (range: 0-18
      years), race/ethnicity (white: 37%; Hispanic: 26.4%; Asian: 15.0%; black: 11.8%;
      other: 8.4%; not stated by parent: 1.6%), and household annual income (range: $10
      524-$175 282). Overall incidence of positive TST results was 1.0% at the 10-mm
      cutoff and 0.5% at the 15-mm cutoff. Positive predictive value of selected
      individual risk factors at the 10-mm cutoff were: child born outside the United
      States, 10.4%; history of receiving bacille Calmette-Guerin vaccine, 5.5%; and
      child having lived outside the United States, 5.3%. Using multivariate analysis,
      we selected a subset of risk factors that were independently and significantly
      associated with a positive TST result >/=10 mm: history of receiving bacille
      Calmette-Guerin vaccine (odds ratio [OR]: 2.31; 95% confidence interval [CI]:
      1.70-3.13); household member with history of positive TST result or TB disease
      (OR: 1.53; 95% CI: 1.14-2.04); child born outside the United States (OR: 8.63;
      95% CI: 6.16-12.09); child having lived outside the United States (OR: 2.06; 95%
      CI: 1.49-2.85); and race/ethnicity reported by parent as Asian (OR: 2.28; 95% CI:
      1.59-3.27) or Hispanic (OR: 1.57; 95% CI: 1.09-2.26). Several factors were not
      statistically significant predictors of a positive TST result: age, sex,
      household annual income, household member infected with human immunodeficiency
      virus or who had stayed in a homeless shelter, and being an adopted or foster
      child. Overall sensitivity of the 9 main items on the questionnaire was 80.9%;
      when a subset of 4 of these questions plus the race/ethnicity questions were
      used, sensitivity of responses was 83.5%. Parents failed to recognize positive
      TST results at a rate of 9.9% (for the 10-mm cutoff) and 5.9% (at the 15-mm
      cutoff). CONCLUSION: A 5-question risk assessment questionnaire completed by
      parents can be used to accurately identify risk factors associated with TB
      infection in children. In our population, some risk factors suggested by the
      American Academy of Pediatrics could not be validated. Parents cannot be relied
      on to read TST results accurately. Screening for TB can be enabled by using a
      standardized, validated questionnaire to identify children who should be given
      tuberculin skin testing.

PMID- 11335776
TI  - The effects of metformin on body mass index and glucose tolerance in obese
      adolescents with fasting hyperinsulinemia and a family history of type 2
      diabetes.
AB  - OBJECTIVES: The prevalence of type 2 diabetes in American adolescents has
      increased markedly during the past generation. Although the factors that
      contribute to the development of type 2 diabetes are complex and not wholly
      elucidated, the triad of severe obesity, hyperinsulinemia, and a family history
      of type 2 diabetes places a child at an increased risk for development of the
      disease. Current approaches to the prevention of type 2 diabetes, including
      dietary counseling and exercise, have had limited success. We reasoned that drugs
      that increase glucose tolerance in diabetic patients might prove useful in
      preventing the progression to glucose intolerance in high-risk patients. To that
      end, we conducted a double-blind, placebo-controlled study of the effects of
      metformin on body mass index (BMI), serum leptin, glucose tolerance, and serum
      lipids in obese adolescents with fasting hyperinsulinemia and a family history of
      type 2 diabetes. METHODS: The study population consisted of 29 white and black
      adolescents aged 12 to 19 years. All had BMIs exceeding 30 kg/m(2). Criteria for
      enrollment included: 1) a fasting insulin concentration exceeding 15 microU/mL;
      and 2) at least 1 first- or second-degree relative with type 2 diabetes. All
      patients had fasting plasma glucose concentrations <110 mg% and hemoglobin A1c
      concentrations </=6.0%. All had normal linear growth and sexual development for
      age, with no marked hirsutism, severe acne, or menstrual irregularities
      characteristic of polycystic ovary syndrome. Eight participants had acanthosis
      nigricans. After baseline laboratory studies including a rapidly sampled
      intravenous glucose tolerance test, patients were randomized to receive metformin
      (500 mg twice daily) or a placebo for a total of 6 months. The effects of
      metformin on BMI standard deviation score, serum leptin, glucose tolerance, and
      serum lipids were analyzed. The study was double-blinded and included no specific
      dietary restrictions. RESULTS: Metformin caused a decline of 0.12 standard
      deviation in BMI in study participants (-1.3% from baseline), and a 5.5%
      reduction in serum leptin in girls. In contrast, BMI and serum leptin rose 0.23
      standard deviation (2.3%) and 16.2%, respectively, in the placebo group during
      the treatment period. Metformin caused a progressive decline in fasting blood
      glucose (from a mean of 84.9 to 75.1 mg%) and a reduction in fasting insulin
      levels (from 31.3 to 19.3 microU/mL). In contrast, fasting glucose levels in the
      placebo group rose slightly from 77.2 to 82.3 mg%, and fasting insulin levels did
      not change. Insulin sensitivity, as assessed by the ratio of fasting insulin to
      glucose concentrations and the quantitative insulin sensitivity check index
      (1/[log fasting insulin + log fasting glucose]) and homeostasis model assessment
      insulin resistance index (fasting insulin x fasting glucose/22.5) indices,
      increased slightly in the metformin-treated participants. However, the insulin
      sensitivity measured using Bergman's minimal model did not change. There were
      also no significant changes in glucose effectiveness, hemoglobin A1c, serum
      lipids, or serum lactate in the metformin or placebo groups. Metformin was
      tolerated well by the majority of patients. Transient abdominal discomfort or
      diarrhea occurred in 40% of treated participants; there were no episodes of
      vomiting or lactic acidosis. CONCLUSIONS: The treatment of obesity and insulin
      resistance in adults often proves ineffective because the vicious cycle leading
      to type 2 diabetes may have become entrenched and, to some extent, may be
      irreversible. Early detection and therapy of the obese adolescent with a family
      history of type 2 diabetes may interrupt the cycle of weight gain and insulin
      resistance that leads to glucose intolerance in adulthood. Through its ability to
      reduce fasting blood glucose and insulin concentrations and to moderate weight
      gain, metformin might complement the effects of dietary and exercise counseling
      and reduce the risk of type 2 diabetes in selected patients.

PMID- 11335777
TI  - The effect of plasma human immunodeficiency virus RNA and CD4(+) T lymphocytes on
      growth measurements of hemophilic boys and adolescents.
AB  - OBJECTIVE: The investigation examined the associations of plasma human
      immunodeficiency virus (HIV) RNA and CD4(+) T lymphocytes with height, weight,
      skeletal maturation, testosterone levels, and height velocity for hemophilic
      children and adolescents with HIV infection in the Hemophilia Growth and
      Development Study. STUDY DESIGN: Two hundred seven participants were evaluated
      over 7 years. RESULTS: A threefold increment in baseline plasma HIV RNA was
      associated with a 0.98-cm decrease in height and a 1.67-kg decrease in weight;
      100-cells/microL decrements in baseline CD4(+) were associated with a 2.51-cm
      decrease in height and a 3.83-kg decrease in weight. Participants with high
      plasma HIV RNA (>3125 copies/mL) experienced significant delay in achieving
      maximum height velocity and lower maximum velocity compared with those with low
      viral load. The high CD4(+) (>243)/low plasma HIV RNA group had earlier age at
      maximum height velocity compared with the other 3 groups and higher maximum
      height velocity compared with the low CD4(+)/high plasma HIV RNA and low
      CD4(+)/low plasma HIV RNA groups. Decrements in CD4(+) were associated with
      decreases in bone age and testosterone level. CONCLUSIONS: CD4(+) and HIV RNA
      were important in predicting growth outcomes.

PMID- 11335778
TI  - Short-term hyperthyroidism followed by transient pituitary hypothyroidism in a
      very low birth weight infant born to a mother with uncontrolled Graves' disease.
AB  - Transient hypothyroxinemia in infants born to mothers with poorly controlled
      Graves' disease was first reported in 1988. We report that short-term
      hyperthyroidism followed by hypothyroidism with low basal thyroid-stimulating
      hormone (TSH) levels developed in a very low birth weight infant born at 27 weeks
      of gestation to a noncompliant mother with thyrotoxicosis attributable to Graves'
      disease. We performed serial thyrotropin-releasing hormone (TRH) tests in this
      infant and demonstrated that TSH unresponsiveness to TRH disappeared at 6.5
      months of age. The maternal thyroid function was free triiodothyronine (FT(3)),
      21.1 pg/mL; free thyroxine (FT(4)), 8.1 ng/dL; TSH, <0.03 microU/mL; thyroid
      stimulating hormone receptor antibody, 52% (normal: <15%); thyroid-stimulating
      antibody, 294% (normal: <180%); and thyroid-stimulation blocking antibody, 9%
      (normal: <25%) on the day of delivery. A nonstress test revealed fetal
      tachycardia >200 beats per minute, and a male infant weighing 1152 g was born by
      emergency cesarean section. Thyroid-stimulating hormone receptor antibody was 16%
      and thyroid-stimulating antibody was 370% in the cord blood. We administered 10
      mg/kg per day of oral propylthiouracil from day 1. Tachycardia along with
      elevated FT(4) and FT(3) levels in the infant decreased from 200/minute to
      170/minute, 4.7 ng/dL to 2.9 ng/dL, 7.0 pg/mL to 4.8 pg/mL, respectively, in the
      first 33 hours. At 5 days, FT(4) and FT(3) were 1.1 ng/dL and 2.9 pg/mL,
      respectively, and we stopped propylthiouracil administration. Although FT(4)
      decreased to 0.4 ng/dL, TSH was quite low and did not respond to intravenous TRH
      by 14 days of age. We began daily levothyroxine 5-micro/kg supplementation. The
      responsiveness of TSH to TRH did not become significant until 4 months old and
      normalized at 6.5 months old. At this time, levothyroxine was stopped. We
      conclude that placental transfer of thyroid hormones may cause hyperthyroidism in
      the fetal and early neonatal periods and lead to transient pituitary
      hypothyroidism in an infant born to a mother with uncontrolled Graves' disease.

PMID- 11335779
TI  - Cisapride decreases gastroesophageal reflux in preterm infants.
AB  - OBJECTIVE: Gastrointestinal prokinetic agents, such as cisapride, are commonly
      used in pediatric practice to improve gastric emptying, to decrease emesis, to
      improve lower esophageal sphincter tone, and to improve irritability and feeding
      aversion associated with gastroesophageal reflux (GER). Although cisapride seems
      to be effective in infants from 2 months to 14 years old, data for younger and
      preterm infants are not available. Whether reflux is a significant cause of
      reflex apnea or feeding intolerance in the preterm infant is controversial. The
      objective of this 1-year prospective study, started in 1998, was to determine the
      efficacy of cisapride for treatment of reflux and reflux-associated apnea (RAAP)
      in preterm infants. Before this study, the diagnosis of reflux was often made
      clinically and the effect of therapy on reflux or the decision to increase the
      dose of cisapride was made empirically. The clinical bias was that persistent
      apnea, not responding to caffeine, was caused by GER. We reasoned that a
      systematic approach to the diagnosis and treatment of reflux would improve the
      care of preterm infants and reduce the risk of toxicity, especially if an
      increased dose of cisapride showed no improvement in reflux or apnea. STUDY
      DESIGN: Twenty-four preterm infants (24-36 weeks' gestational age) had clinical
      apnea/pH studies when they were referred by the attending neonatologist for
      suspected GER. These infants were born at 28.8 +/- 3.1 weeks with birth weight of
      1169 +/- 387 g (range: 631-2263 g). Each infant was studied before and 8 days
      after starting cisapride treatment. Cisapride dose was 0.09 to 0.25 mg/kg every 6
      hours enterally. Treatment decisions regarding dose of cisapride were the
      responsibility of the attending neonatologist. The pH was recorded continuously
      for 24 hours at 0.25 Hz and was analyzed using EsopHogram software. A single
      sensor pH catheter was inserted to ~2 cm above the esophageal gastric junction.
      GER was defined as a drop in esophageal pH below 4.0 for a least 5 seconds, or
      pathologic GER was defined as a reflux index (RI) >2 standard deviation (SD) from
      the mean based on published norms for term infants. The following parameters were
      calculated from the pH recording: number of reflux events per 24 hours, duration
      of the longest episode, number of episodes >5 minutes per 24 hours, and RI, ie,
      percentage of time with pH <4.0. Each study had a combined time-lapse video
      recording and multichannel digital recording. Recorded parameters were:
      continuous pulse oximetry, electrocardiogram, respiratory effort (piezo sensor),
      and airflow (temperature sensor at nostrils and mouth). The recording was scored
      for central apneas of 10 to 14 seconds and >/=15 seconds (prolonged) and >/=10
      seconds for obstructive and mixed apneas. RAAP was scored when an apnea
      (irrespective of the type) occurred within 1 minute of a GER event. Baseline,
      after cisapride, and follow-up electrocardiograms were performed because of
      concern about prolonged QTc and cardiac arrhythmias. The infants were 35.6 +/-
      4.5 weeks postconceptional age when first studied. Twelve infants (mean birth
      weight: 1821 +/- 749 g; gestational age: 32 +/- 2 weeks; postconceptional age:
      35.6 +/- 2.6 weeks) were identified retrospectively as controls because their
      baseline GER parameters were within the normal range using Vandenplas' criteria.
      RESULTS: Overall, cisapride treatment significantly improved the RI from 16.6 +/-
      15.2 to 9.1 +/- 8.4 SD. The number of reflux episodes >/=5 minutes was reduced
      from 7.1 +/- 5.8 to 4.3 +/- 4.4 SD. No significant effect was seen on the total
      number of refluxes (/24 hours). Eight infants (33%) had no decrease in the RI
      after a week of treatment. Three of these infants improved after cisapride dose
      was increased from 0.09 to 0.25 mg/kg/dose every 6 hours. Although 0.09 mg/kg/day
      is the minimum effective dose, 67% of our infants did respond to this low dose.
      Cisapride was discontinued in 3 infants because of prolonged QTc >/=0.450 seconds
      (0.473 in 1 and 0.470 in 2). More data about the effect of cisapride on QTc
      interval are reported in Pediatrics in a separate article. Only 1 infant showed
      no improvement with increased dose. Caffeine treatment had no effect on the
      baseline or follow-up GER values. Although apnea indexes for central and
      obstructive apnea were similar before and after cisapride, mixed apnea was less
      during treatment. There was a significant decrease (0.32 +/- 0.40 to 0.12 +/-
      0.17/hour) in RAAP when the one infant who had increased reflux on increased dose
      of cisapride was excluded as an outlier. The statistical difference, before and
      after cisapride, for the group is significant with the outlier omitted. The
      clinical significance is unclear because ~50% of the infants had minimal changes
      in their apnea indexes. Furthermore, ~40% of infants did not have RAAP. (ABSTRACT
      TRUNCATED)

PMID- 11335780
TI  - Size at birth predicts age at menarche.
AB  - OBJECTIVE: This study examines the relationship of intrauterine growth, measured
      by size and maturity at birth, to age at menarche, while also considering a wide
      range of other factors that may affect maturation. The research is motivated by
      the current debate about the importance of the prenatal environment as a
      determinant of later disease risk. METHODS: Data were collected during the Cebu
      Longitudinal Health and Nutrition Survey. This community-based study has followed
      a cohort of several thousand Filipino infants since their birth in 1983 to 1984.
      Participants live in urban and rural communities of Metro Cebu, the second
      largest metropolitan area of the Philippines. The analysis sample includes 997
      girls 14 to 15 years of age. The main outcome measure is age at menarche,
      determined from girls' self-report of the month and year of first menses. Factors
      that influenced age at menarche were identified using Weibull parametric survival
      time models. The main exposure variables of interest included weight and length
      (measured by trained field staff) and gestational age (assessed from mother's
      reported date of last menstrual period, augmented by clinical assessments at
      birth). The analysis also takes into account a wide range of other factors that
      are likely to affect age at menarche. These include the girls' early postnatal
      growth rates, premenarcheal body composition (body mass index and skinfold
      thicknesses measured at 8 years), current diet (measured by two 24-hour dietary
      recalls), and socioeconomic conditions of the household in which they live. We
      also assessed the contribution of maternal characteristics, including age at
      menarche, height, and nutritional status while pregnant with the study child.
      RESULTS: The median age at menarche calculated from the hazard model is 13.1
      years, with 50% of girls attaining menarche between 12.4 and 13.9 years. Earlier
      menarche is characteristic of girls who live in urban, higher socioeconomic
      status households, as indicated by higher maternal education, better housing
      quality, and possession of assets, such as a TV or refrigerator. Age at menarche
      is significantly associated with birth characteristics. Although birth weight
      alone was not significantly related to age at menarche, girls who were relatively
      long and thin at birth (>49 cm, <3 kg) attained menarche ~6 months earlier than
      did girls who were short and light (<49 cm, <3 kg). This effect of thinness at
      birth is most pronounced among girls with greater than average growth increments
      in 6 months of life. The effects of birth size are not modified when body mass
      index and skinfold thicknesses at 8 years are taken into account. Effects of
      birth size on age at menarche also remain significant when maternal nutritional
      status during pregnancy and the girl's current diet and socioeconomic indicators
      are taken into account. CONCLUSIONS: The study provides additional evidence of
      fetal programming of later health outcomes by showing that future growth and
      maturation trajectories are established in utero. Furthermore, rapid postnatal
      growth potentiates the effects of size at birth and is related independently to
      earlier pubertal maturation.

PMID- 11335781
TI  - Sleep and behavior problems in school-aged children.
AB  - OBJECTIVES: The primary purposes of the present study were to survey the
      prevalence of sleep problems in school-aged children and to examine these
      associations with parental perception of sleep problems, medical history, and
      childhood psychopathology. METHODS: Sleep and medical history questionnaires and
      the Child Behavior Checklist were administered to the parents of 472 children
      between ages 4 and 12 years receiving routine pediatric care from urban, rural,
      and suburban pediatric practices. RESULTS: Although sleep problems were reported
      for 10.8% of the sample during the past 6 months, less than one half of the
      parents who identified sleep problems reported that they had discussed sleep with
      their child's pediatrician. The best predictor of current sleep problems was a
      history of sleep problems before age 2 years. Sleep problems such as snoring,
      tiredness during the day, and taking excessive time to fall asleep were very
      common, occurring at least 1 night per week in over 20% of the total sample.
      Factor analysis of the sleep problems questionnaire resulted in 5 sleep problem
      factors that accounted for 58.7% of the variance. Specific sleep problem factors
      include: parasomnias, enuresis/gags, tiredness, noisy sleep, and insomnia. Sleep
      problem factor scores were differentially associated with medical history
      variables and measures of childhood psychopathology. Children rated highly on
      parasomnias were more likely to have frequent falls and to display pica.
      Parasomnias and noisy sleep were inversely associated with socioeconomic status
      (SES). Children from lower SES families were rated higher on these factors than
      children from higher SES families. Enuresis/gags was the only sleep problem
      factor associated with age. Younger children scored higher on this factor.
      Duration of naps was highly correlated with age and with bed times during the
      week and weekends. As expected, younger children were more likely to nap for
      longer periods and to have earlier bed times. In addition, higher tiredness
      factor scores were associated with napping and with later bed times during the
      week and weekend. Boys were much more likely than were girls to have higher
      scores on enuresis/gags, and higher enuresis/gags scores were associated with an
      increased prevalence of trauma and falls. Bed times were not associated with any
      other sleep problem factor score. Children rated highly on tiredness were more
      likely to have a history of hospitalizations. Tiredness factor scores were
      strongly associated with the sleep practice of sharing a bed but not with sharing
      a room. Sharing a room was not associated with any sleep problem factor score.
      High scores on noisy sleep were associated with allergies, falls frequently, and
      with sharing a bed. Children with high scores on the insomnias were also more
      likely to display an increased prevalence of allergies. CONCLUSIONS: Parental
      perception of global sleep problems was surprisingly common in school-aged
      children receiving routine pediatric care. Parental reports of their children's
      sleep problems may be a red flag for specific sleep problems and psychiatric,
      social, or medical problems. Sleep problems should be queried about during
      pediatric visits for school-aged children.

PMID- 11335782
TI  - Shortening the questionnaire for identifying children with chronic conditions:
      what is the consequence?
AB  - OBJECTIVE: To determine whether a reduced item set can identify children who have
      chronic conditions with a level of at least 90% accuracy compared with the
      complete Questionnaire for Identifying Children With Chronic Conditions (QuICCC).
      BACKGROUND: The QuICCC was developed to operationalize a conceptually based,
      noncategorical definition of chronic conditions developed by Stein et al. It
      contains 39 item sequences administered to a parent that assess 3 types of
      consequences: functional limitations; reliance on compensatory mechanisms or
      assistance; and service use or need above usual for age. The QuICCC has been
      validated and widely adopted as a means of identifying children without using a
      diagnosis checklist, but there is considerable interest in shortening it.
      DESIGN/METHODS: Through secondary analyses of 3 data sets (Ns = 1265, 1388, and
      4831), we identified a short list of items that identified >90% of children who
      were identified by the 39-item QuICCC. We administered these 16 items to 2 new
      samples of parents. In Study 1 we administered the 16 items in the shortened
      version first, followed by the other 23 items, and compared the results on the
      short and reordered long versions. In Study 2, the 39- and 16-item versions were
      each administered, one in person and the other by phone, in random order to the
      same respondent within a 2-week period. These data were analyzed to compare the
      short and longer versions at the 2 time points and within the single, longer 39
      item format (simultaneous data). RESULTS: In Study 1 (N = 630) only 4 children
      were missed by the 16-item version who were identified by the longer version
      (sensitivity 98.6%; specificity 100%; positive predictive value 100%; negative
      predictive value 98.8% kappa 0.987). In Study 2 (N = 552), no children were
      missed by the 16-item subset of the 39 items when looking at the simultaneous
      data. When the two forms were administered 2 weeks apart, the 16-item version had
      a sensitivity of 87%, specificity of 90%, positive predictive value of 93%,
      negative predictive value of 82%, and kappa of 0.78 compared with the longer
      QuICCC. These results correspond exactly to the data obtained in a 2-week test
      retest study for the QuICCC itself. The new form (the QuICCC-R) takes <2 minutes
      to administer on average (range 1-4 minutes) compared with 7 to 8 minutes for the
      full QuICCC. CONCLUSIONS: The results met our criteria for agreement, and we
      conclude that the QuICCC-R is a satisfactory alternative for screening
      populations. However, the full QuICCC has other applications beyond screening
      that may not apply to the QuICCC-R, the shorter version.

PMID- 11335783
TI  - Tolerability and effectiveness of prochlorperazine for intractable migraine in
      children.
AB  - OBJECTIVE: To study the effectiveness of prochlorperazine in aborting severe,
      intractable migraines in children. STUDY DESIGN: Patients for this study were
      drawn from the population seen and evaluated in the Headache Center at Cincinnati
      Children's Hospital Medical Center. All patients were diagnosed with migraine
      headache by both clinical and International Headache Society criteria. The
      effectiveness of intravenous prochlorperazine in 20 consecutive patients referred
      to the emergency department for severe, prolonged migraines was retrospectively
      reviewed. RESULTS: Patients evaluated in this study presented with a mean
      headache severity of 8.4 on a 0- to 10-point scale and an average duration of 54
      hours. At 1 hour, 90% of the patients reported feeling better with 50% becoming
      pain-free. A 50% or greater reduction in severity occurred in 75% of patients at
      1 hour and in 95% at 3 hours. At 3 hours, 95% of the patients reported feeling
      better, and 60% were pain-free. Only 1 patient failed to respond to
      prochlorperazine. CONCLUSION: Prochlorperzaine was shown to be highly effective
      in aborting intractable migraines in children. It was well tolerated with no
      significant side effects. Additional large, double-blinded, randomized, placebo
      controlled studies are needed to further investigate its effectiveness.

PMID- 11335784
TI  - Prenatal, perinatal, and neonatal factors in autism, pervasive developmental
      disorder-not otherwise specified, and the general population.
AB  - OBJECTIVES: To examine various pre-, peri-, and neonatal factors in autistic
      participants and in pervasive developmental disorder-not otherwise specified (PDD
      NOS) participants and to compare the incidence of each factor to that of the
      normal population. METHODS: Seventy-four participants (66 males, 8 females) were
      diagnosed with autism at 2.5 through 4 years of age using the most accurate and
      up-to-date methods, including the Diagnostic and Statistical Manual of Mental
      Disorders and the Autism Diagnostic Interview-Revised. At age 5, all participants
      were reevaluated using the Diagnostic and Statistical Manual of Mental Disorders,
      the Autism Diagnostic Interview-Revised, the Childhood Autism Rating Scale, and
      the Autism Diagnostic Observation Schedule-Revised, resulting in 61 autistic and
      13 PDD-NOS participants. Twenty-eight pre-, peri-, and neonatal factors were
      examined in these 2 groups using both medical records and parental interviews.
      Incidences were compared with those of the US population as reported in the
      Report of Final Natality Statistics, 1995. This grand scale population group was
      used to closely approximate comparison to a normal, unbiased population. Results
      were analyzed using the binomial probability test, with a P value of <.05,
      constituting a significant difference in incidence. A Bonferroni correction was
      applied to the data to adjust for the number of factors investigated. RESULTS:
      Although most of the factors showed comparable incidences between the index and
      control groups, several factors showed statistically significant differences.
      Following the Bonferroni correction, the autism group was found to have a
      significantly higher incidence of uterine bleeding, a lower incidence of maternal
      vaginal infection, and less maternal use of contraceptives during conception when
      compared with the general population. Similarly, the PDD-NOS group showed a
      higher incidence of hyperbilirubinemia when compared with the general population.
      CONCLUSIONS: The results of this study support previous findings suggesting a
      consistent association of unfavorable events in pregnancy, delivery, and the
      neonatal phase and the pervasive developmental disorders. However, interpretation
      of the meaningfulness of these results is difficult, as the specific
      complications that carried the highest risk of autism and PDD-NOS represented
      various forms of pathologic processes with no presently apparent unifying
      feature. Additional studies are needed to corroborate and strengthen these
      associations, as well as to determine the possibility of an underlying unifying
      pathological process. This study's analysis of obstetric and neonatal
      complications in combination with the use of participants diagnosed at an early
      age provides some interesting concepts to consider. Perhaps future research will
      confirm certain pre-, peri-, and neonatal associations that could be used to
      generate a high-risk historical profile with which to use in conjunction with
      currently employed diagnostic tools. This may, in turn, help to determine the
      reliability of a diagnosis of autism in younger children, leading to earlier
      intervention and assistance for an improved outcome in long-term functionality
      and quality of life.

PMID- 11335785
TI  - Non-viral vectors in cancer gene therapy: principles and progress.
AB  - This review focuses on the use of synthetic (non-viral) delivery systems for
      cancer gene therapy. Therapeutic strategies such as gene replacement/mutation
      correction, immune modulation and molecular therapy/'suicide' gene therapy type
      approaches potentially offer unique and novel ways of fighting cancer, some of
      which have already shown promise in early clinical trials. However, the specific
      and efficient delivery of the genetic material to remote tumors/metastases
      remains a challenge, which is being addressed using a variety of viral and non
      viral systems. Each of these disparate systems has distinct advantages and
      disadvantages, which need to be taken into account when a specific therapeutic
      gene is being used. The review concentrates on particulate gene delivery systems,
      which are formed through non-covalent complexation of cationic carrier molecules
      (e.g. lipids or polymers) and the negatively charged plasmid DNA. Such systems
      tend to be comparatively less efficient than viral systems, but have the inherent
      advantage of flexibility and safety. The DNA-carrier complex acts as a protective
      package, and needs to be inert and stable while in circulation. Once the remote
      site has been reached the complex needs to efficiently transfect the targeted
      (tumor) cells. In order to improve overall transfection specificity and
      efficiency it is necessary to optimize intracellular trafficking of the DNA
      complex as well as the performance after systemic administration. Common
      principles and specific advantages or disadvantages of the individual synthetic
      gene delivery systems are discussed, and their interaction with tumor-specific
      and generic biological barriers are examined in order to identify potential
      strategies to overcome them.

PMID- 11335786
TI  - A new prodrug of paclitaxel: synthesis of Protaxel.
AB  - 2' and 7 Polyol carbonates of paclitaxel were synthesized and screened as
      potential paclitaxel prodrugs. Paclitaxel is released from 7-(2",3"
      dihydroxypropylcarbonato) paclitaxel (Protaxel) at rates inversely proportional
      to pH, by an intramolecular cyclization. Compared to paclitaxel, maximum
      tolerated i.v. or i.p. doses (MTD) of Protaxel are about 2.5- to 3-fold higher;
      its efficacy is substantially higher in human cancer line xenografts in athymic
      mice, especially in prostate PC-3, breast MDA-MB 468 and ovary OVCAR-1.

PMID- 11335787
TI  - Phase I clinical and pharmacokinetic study of PNU166945, a novel water-soluble
      polymer-conjugated prodrug of paclitaxel.
AB  - Intravenous administration of paclitaxel is hindered by poor water solubility of
      the drug. Currently, paclitaxel is dissolved in a mixture of ethanol and
      Cremophor EL; however, this formulation (Taxol) is associated with significant
      side effects, which are considered to be related to the pharmaceutical vehicle. A
      new polymer-conjugated derivative of paclitaxel, PNU166945, was investigated in a
      dose-finding phase I study to document toxicity and pharmacokinetics. A clinical
      phase I study was initiated in patients with refractory solid tumors. PNU16645
      was administered as a 1-h infusion every 3 weeks at a starting dose of 80
      mg/m(2), as paclitaxel equivalents. Pharmacokinetics of polymer-bound and
      released paclitaxel were determined during the first course. Twelve patients in
      total were enrolled in the study. The highest dose level was 196 mg/m(2), at
      which we did not observe any dose-limiting toxicities. Hematologic toxicity of
      PNU166945 was mild and dose independent. One patient developed a grade 3
      neurotoxicity. A partial response was observed in one patient with advanced
      breast cancer. PNU166945 displayed a linear pharmacokinetic behavior for the
      bound fraction as well as for released paclitaxel. The study was discontinued
      prematurely due to severe neurotoxicity observed in additional rat studies. The
      presented phase I study with PNU166945, a water-soluble polymeric drug conjugate
      of paclitaxel, shows an alteration in pharmacokinetic behavior when paclitaxel is
      administered as a polymer-bound drug. Consequently, the safety profile may differ
      significantly from standard paclitaxel.

PMID- 11335788
TI  - Increased sensitivity to cytosine arabinoside in human leukemia by c-raf-1
      antisense oligonucleotides.
AB  - c-raf-1, a cytoplasmic serine/threonine protein kinase, plays an important role
      in mitogen- and damage-responsive cellular signal transduction pathways.
      Expression of c-raf-1 modifies cell growth, proliferation and survival. Although
      expression of c-raf-1 has been studied in several tumors, the role of c-raf-1 in
      leukemia is so far unclear. We examined the expression of c-raf-1 in the human
      leukemia cell lines U937 and K562, and in a cytosine arabinoside (Ara-C)
      resistant cell line (K562AC) derived from K562. Expression of c-raf-1 was
      increased in U937 and in Ara-C-resistant K562AC cells compared with the parental
      cells. We then investigated whether inhibition of c-raf-1 expression by antisense
      oligonucleotides increases the sensitivity to Ara-C in U937 and K562AC cells.
      Antisense oligonucleotides for c-raf-1 inhibited expression of c-raf-1 mRNA, but
      did not affect cell growth and increased sensitivity to Ara-C but not to other
      drugs such as adriamycin, VP-16 or vincristine. These results suggest that c-raf
      1 is one of the factors involved in Ara-C resistance in leukemia and lend weight
      to the case for development of anti-cancer therapeutics involving oncogene
      targeted antisense oligonucleotides.

PMID- 11335789
TI  - Intra-arterial plus i.v. chemotherapy for advanced bulky squamous cell carcinoma
      of the buccal mucosa.
AB  - From July 1994 to December 1996, 41 patients with previously untreated, advanced
      bulky squamous cell carcinoma arising from the buccal mucosa (BSCC) were
      enrolled. All patients were males with a median age of 47 years (range 29-72).
      The tumor extent was stage III/IV: three of 38, T4: 85%, N2-3: 20%. Patients were
      initially scheduled to receive intra-arterial (i.a.) chemotherapy, followed by
      i.v. chemotherapy and regional therapy. The i.a. chemotherapy catheter was
      properly placed by external carotid artery angiography via the femoral artery.
      The i.a. chemotherapy consisted of cisplatin (P) 100 mg/m(2) day 1 plus 5
      fluorouracil (F) 1000 mg/m(2) day 1-4, and the i.v. chemotherapy consisted of PF
      (10 patients) or PF plus methotrexate 200 mg/m(2) day 15 and 22 (31 patients).
      All chemotherapy regimens were administered at 4-week intervals. The response
      rate of i.a. plus i.v. chemotherapy for the primary site was 85% (35 of 41) with
      29% complete remission (CR) (12 of 41). The response and CR rates of neck nodes
      were 82% (14 of 17) and 41% (seven of 17), respectively. The combined overall
      response rate was 80% (33 of 41) with a 29% CR (12 of 41). Major toxicity from
      i.a. chemotherapy of WHO grade > or = 3 included: mucositis of infusion area
      (76%), hemialopecia (56%) and leukopenia (5%). Three neurologic complications of
      i.a. chemotherapy including one hemiparesis occurred. The median follow-up time
      was 47 months (range 36-66 months), and the overall survival and disease-free
      survival were both 34% (14 of 41). Four patients were cured with chemotherapy
      alone and eight patients (19.5%) were cured without surgical intervention. Using
      i.a. chemotherapy as a cytoreductive therapy followed by subsequent i.v.
      chemotherapy produces a high response rate and an encouraging degree of complete
      response rate in advanced bulky BSCC. However, toxicity management and catheter
      placement will need to be improved in order to better define the role of this
      therapy in advanced BSCC.

PMID- 11335790
TI  - Mitomycin C with weekly 24-h infusion of high-dose 5-fluorouracil and leucovorin
      in patients with biliary tract and periampullar carcinomas.
AB  - We have reported a 33% partial response rate with acceptable toxicity using
      weekly 24-h infusion of high-dose 5-fluorouracil (5-FU) and leucovorin (LV) in
      patients with far advanced biliary tract cancers (BTC). In this study, we added
      mitomycin (MMC) to 5-FU and LV in an attempt to improve the response rate and
      survival. From July 1997 to September 1999, 25 chemotherapy-naive patients with
      pathology-proven far advanced BTC and periampullar cancers were enrolled. The
      regimen consisted of MMC 10 mg/m(2) every 8 weeks combined with 5-FU 2600 mg/m(2)
      and LV 150 mg at a schedule of 24-h infusion weekly for 6 weeks followed by a 2
      week break. There were 10 males and 15 females with a median age of 57 years
      (range 40-76). The sites of primary tumor were 15 intrahepatic
      cholangiocarcinomas (CC), one perihilar CCs, three distal BTC, three gallbladder
      cancers (GB) and three periampullar cancers. A total of 148 sessions of
      chemotherapy were given with a mean of 8 (range 2-18). Nineteen patients were
      evaluable for response. The response rate was: 26% (five of 19) partial response,
      42% (eight of 19) stable disease and 32% (six of 19) progressive disease. All of
      the patients were evaluable for toxicity. Toxicities more than grade III-IV were
      thrombocytopenia 16% (four of 25), leukopenia 12% (three of 25) and vomiting 4%
      (one of 25). There were four treatment-related deaths. The median time to disease
      progression was 3 months. The median survival was 6 months. A combination of MMC
      with weekly high-dose 5-FU and LV in patients with BTC did not improve the
      response rate, but produced more toxicity than weekly high-dose 5-FU and LV
      alone.

PMID- 11335791
TI  - Tolerability of the cytoprotective agent amifostine in elderly patients receiving
      chemotherapy: a comparative study.
AB  - In order to determine if age and comorbidity influence the tolerability of the
      cytoprotective agent amifostine, we compared side effects related to amifostine
      in patients > or = 70 years (group I) with patients < 70 years (group II). We
      evaluated 268 consecutive administrations of amifostine (119 in group I and 149
      in group II, respectively), given i.v. at a dose of 740 mg/m(2) just before
      platinum-, taxol- or cyclophosphamide-based chemotherapy. Transient hypotension
      was the most common side effect occurring in association with amifostine.
      Decreases in systolic blood pressure > 20 mmHg were of similar frequency in both
      groups (27.1 versus 28.8% of amifostine infusions in group I and II,
      respectively). Hypotension did not result in medical sequelae in any of the
      patients. The amifostine infusion was interrupted 16 times in group I and 8 times
      in group II, respectively, mainly due to hypotension, but could be restarted
      after a few minutes in all patients except for three cases in group I. Patients
      in group II more often suffered from nausea/vomiting than in group II (20.8
      versus 10.0% in group I). Other subjective symptoms (e.g. warmed, flushed
      sensation, sneezing, metallic taste, mouth dryness, dizziness and sleepiness) and
      hypocalcemia occurred with a similar frequency in both groups. Adverse effects
      associated with amifostine were not observed more frequently in elderly patients
      than in younger ones, although more elderly patients had a comorbidity than the
      younger ones.

PMID- 11335792
TI  - The effect of different doses of cyclosporin A on the systemic exposure of orally
      administered paclitaxel.
AB  - The objective of this study was to define the minimally effective dose of
      cyclosporin A (CsA) that would result in a maximal increase of the systemic
      exposure to oral paclitaxel. Six evaluable patients participated in this
      randomized cross-over study in which they received at two occasions two doses of
      90 mg/m(2) oral paclitaxel 7 h apart in combination with 10 or 5 mg/kg CsA. Dose
      reduction of CsA from 10 to 5 mg/kg resulted in a statistically significant
      decrease in the area under the plasma concentration-time curve (AUC) and time
      above the threshold concentrations of 0.1 microM (T>0.1 microM) of oral
      paclitaxel. The mean (+/-SD) AUC and T>0.1 microM values of oral paclitaxel with
      CsA 10 mg/kg were 4.29+/-0.88 microM x h and 12.0+/-2.1 h, respectively. With CsA
      5 mg/kg these values were 2.75+/-0.63 microM x h and 7.0+/-2.1 h, respectively
      (p=0.028 for both parameters). In conclusion, dose reduction of CsA from 10 to 5
      mg/kg resulted in a significant decrease in the AUC and T>0.1 microM values of
      oral paclitaxel. Because CsA 10 mg/kg resulted in similar paclitaxel AUC and
      T>0.1 microM values compared to CsA 15 mg/kg (data which we have published
      previously), the minimally effective dose of CsA is determined at 10 mg/kg.

PMID- 11335794
TI  - Vanadocenes as potent anti-proliferative agents disrupting mitotic spindle
      formation in cancer cells.
AB  - We present experimental data which establish the organometallic compounds
      vanadocene dichloride (VDC) and vanadocene acetylacetonate (VDacac) as potent
      anti-proliferative agents. We first examined the effects of VDC and VDacac on the
      rapid embryonic cell division and development of Zebrafish. Both compounds were
      capable of causing cell division block at the 8-16 cell stage of embryonic
      development followed by total cell fusion and developmental arrest. We next
      examined the effect of VDC and VDacac on proliferation of human breast cancer and
      glioblastoma cell lines using MTT assays. VDC inhibited the proliferation of the
      breast cancer cell line BT-20 as well as the glioblastoma cell line U373 in a
      concentration-dependent fashion with IC50 values of 11.0, 14.9 and 18.6 microM,
      respectively. VDacac inhibited cellular proliferation with IC50 values of 9.1,
      26.9 and 35.5 microM, respectively. Whereas in vehicle-treated control cancer
      cells mitotic spindles were organized as a bipolar microtubule array and the DNA
      was organized on a metaphase plate, vanadocene-treated cancer cells had aberrant
      monopolar mitotic structures where microtubules were detected only on one side of
      the chromosomes and the chromosomes were arranged in a circular pattern. In
      contrast to control cells which showed a single focus of gamma-tubulin at each
      pole of the bipolar mitotic spindle, VDC- or VDacac-treated cells had two foci of
      gamma-tubulin on the same side of the chromosomes resulting in a broad centrosome
      at one pole. All monopolar spindles examined had two foci of gamma-tubulin
      labeling consistent with a mechanism in which the centrosomes duplicate but do
      not separate properly to form a bipolar spindle. These results provide
      unprecedented evidence that organometallic compounds can block cell division in
      human cancer cells by disrupting bipolar spindle formation. In accordance with
      these results vanadocene treatment caused an arrest at the G2/M phase of the cell
      cycle. This unique mechanism of anti-mitotic function warrants further
      development of vanadocene complexes as anti-cancer drugs.

PMID- 11335795
TI  - Prevention of growth of human lung carcinoma cells and induction of apoptosis by
      a novel phenoxazinone, 2-amino-4,4alpha-dihydro-4alpha,7-dimethyl-3H-phenoxazine
      3-one.
AB  - Anti-tumor effects of a novel phenoxazinone, 2-amino-4,4-dihydro-4alpha,7
      dimethyl-3H-phenoxazine-3-one (Phx), which was synthesized by the reaction of 2
      amino-5-methylphenol with bovine hemoglobin, were studied in terms of suppression
      of the proliferation of human lung carcinoma cells and apoptosis induction. When
      Phx was added to cultures of the human lung carcinoma cell lines A549
      (adenocarcinoma) and H226 (squamous carcinoma), it caused the growth inhibition
      and the death of these cells. Phx also fragmented the DNA of these cells to
      oligonucleosomal-sized fragments, which is characteristic of the apoptosis,
      dependent on the dose and exposure time. The cellular death caused by the
      administration of Phx was partially reversed by the addition of Z-VAD-fmk, a
      caspase family inhibitor. Present results suggest that Phx demonstrates anti
      cancer activity against human lung carcinoma cell lines A549 and H226, by
      inhibiting growth and inducing apoptosis.

PMID- 11335793
TI  - Antitumor activity of XR5944, a novel and potent topoisomerase poison.
AB  - Inhibitors of topoisomerases are widely used in the treatment of cancer,
      including inhibitors of topoisomerase I (camptothecin analogs such as irinotecan
      and topotecan) and topoisomerase II (etoposide and doxorubicin). The novel bis
      phenazine, XR5944, is a joint inhibitor of topoisomerase I and II as shown by the
      stabilization of topoisomerase-dependent cleavable complexes. XR5944 demonstrated
      exceptional activity against human and murine tumor cells in vitro and in vivo.
      In a range of cell lines XR5944 (IC50 0.04-0.4 nM) was significantly more potent
      than TAS-103, originally proposed as a joint topoisomerase I and II inhibitor, as
      well as agents specific for topoisomerase I or II (topotecan, doxorubicin and
      etoposide). In addition, XR5944 was unaffected by atypical drug resistance and
      retained significant activity in cells overexpressing P-glycoprotein or multidrug
      resistance-associated protein. Antitumor efficacy of XR5944 was demonstrated in
      human carcinoma xenograft models (H69 small cell lung cancer and HT29 colon). In
      the HT29 model, which is relatively unresponsive to chemotherapy, XR5944 (15
      mg/kg i.v., q4dx3) induced tumor regression in the majority of animals (six of
      eight), whereas TAS-103, dosed at its maximum tolerated dose (45 mg/kg i.v.,
      q7dx3), only induced a delay in tumor growth compared with control animals. In
      the H69 model, low doses of XR5944 (5 mg/kg i.v., qdx5/week for 2 weeks or 10-15
      mg/kg i.v., q4dx3), induced complete tumor regression in the majority of animals.
      In contrast, topotecan (20 mg/kg i.v., q4dx3) or etoposide (30 mg/kg i.v., q5dx5)
      only slowed the tumor growth rate. These studies show that XR5944 is a highly
      active novel anticancer agent that is well tolerated at efficacious doses.

PMID- 11335796
TI  - Incidence of thrombocytopenia with gemcitabine-based therapy and influence of
      dosing and schedule.

PMID- 11335797
TI  - Differential expression of fibroblast growth factor receptors in human digital
      development suggests common pathogenesis in complex acrosyndactyly and
      craniosynostosis.
AB  - The Apert hand is characterized by metaphyseal fusions of the metacarpals and
      distal phalanges, symphalangism, and soft-tissue syndactyly. More subtle skeletal
      anomalies of the limb characterize Pfeiffer and Crouzon syndromes. Different
      mutations in the fibroblast growth factor receptor 2 (FGFR2) gene cause these
      syndromes, and offer the opportunity to relate genotype to phenotype. The
      expression of FGFR1 and of the Bek and KGFR isoforms of FGFR2 has, therefore,
      been studied in human hand development at 12 weeks by in situ hybridization.
      FGFRs are differentially expressed in the mesenchyme and skeletal elements during
      endochondral ossification of the developing human hand. KGFR expression
      characterizes the metaphyseal periosteum and interphalangeal joints. FGFR1 is
      preferentially expressed in the diaphyses, whereas FGFR2-Bek expression
      characterizes metaphyseal and diaphyseal elements, and the interdigital
      mesenchyme. Apert metaphyseal synostosis and symphalangism reflect KGFR
      expression, which has independently been quantitatively related ex vivo to the
      severity of clinical digital presentations in these syndromes. Studies in avian
      development implicate FGF signaling in preventing interdigital apoptosis and
      maintaining the interdigital mesenchyme. Herein is proposed that in human FGFR
      syndromes the balance of signaling by means of KGFR and Bek in digital
      development determines the clinical severity of soft-tissue and bony syndactyly.

PMID- 11335798
TI  - Reconstructive management of cranial base defects after tumor ablation.
AB  - Successful reconstruction after cranial base tumor ablation is paramount in
      preventing potentially life-threatening complications. The purpose of this study
      was to evaluate experiences of cranial base reconstruction and to identify
      reconstructive management principles that may assist in achieving successful
      cranial base reconstruction. All cranial base reconstructions performed by the
      Department of Plastic Surgery at the University of Texas M. D. Anderson Cancer
      Center between January of 1993 and September of 1999 were reviewed. Analyses were
      performed to assess the impact of location of defect, type of reconstruction,
      type of dural repair, and history of preoperative radiation and chemotherapy on
      rates of complications, and patient survival. The 77 patients who underwent
      cranial base reconstruction after tumor ablation during the study period had a
      mean age of 52 years (6 to 84 years). The mean follow-up period was 28.7 months
      (1 to 76 months). Squamous cell carcinoma, the most common histopathologic type,
      was present in 24 patients (31 percent), and 35 patients (45 percent) presented
      with recurrent disease. Location of defects involved region I (anterior) in 31
      patients (40 percent), region II (anterior-lateral) in 18 (23 percent), region
      III (lateral-posterior) in six (8 percent), and more than one region in 22 (29
      percent). Reconstructive methods included free flaps in 52 patients (68 percent),
      temporalis muscle flaps in 14 (18 percent), pericranial flaps in eight (10
      percent), and other local flaps (two galeal, one scalp) in three (4 percent). Of
      the 52 free flaps, 18 (35 percent) were used in region I, 14 (27 percent) in
      region II, six (12 percent) in region III, and 14 (27 percent) in defects
      involving more than one region. Of the 14 temporalis muscle flaps, 13 (93
      percent) were used for defects involving regions I or II and one (7 percent) was
      used for a defect involving region III. Of the 11 pericranial and other local
      flaps, nine (82 percent) were used in region I, one (9 percent) in region II, and
      one (9 percent) in a combination of regions II and III. Complications occurred in
      21 patients (27 percent): three total flap losses (4 percent), three partial flap
      losses (4 percent), two cerebrospinal fluid leaks (3 percent), two cases of
      meningitis (3 percent), two abscesses (3 percent), five cases of delayed wound
      healing (6 percent), two hematomas (3 percent), one wound infection (1 percent),
      and one cerebrovascular accident (1 percent). Overall survival was 77 percent at
      2 years and 58 percent at 4 years. The type of reconstruction, location of
      defect, type of dural repair, and history of preoperative radiation and
      chemotherapy had no significant association with the incidence of complications.
      Neither the type of reconstruction nor the location of defect showed a
      significant effect on patient survival. In this experience, local flaps, such as
      pericranial or temporalis muscle flaps, are good choices for reconstruction of
      smaller anterior or lateral cranial base defects. For defects that require larger
      amounts of soft tissue, free flaps are appropriate. With proper patient
      selection, successful cranial base reconstruction can be performed with either
      local or free flaps with a low incidence of complications.

PMID- 11335800
TI  - Reconstruction of large nasal defects with a combination of local flaps based on
      the aesthetic subunit principle.
AB  - Herein is described a technique that uses a combination of local flaps to
      reconstruct large defects involving the nasal dorsum and cheek. The flaps used
      are a transposition flap elevated from the area adjoining the defect and
      bilateral cheek advancement flaps. This technique leaves all suture wounds at
      borders of the aesthetic subunits that have been described previously. Color and
      texture matches were good and symmetrical. The transposition flap can be modified
      according to whether the defect includes the nasal tip. After raising the cheek
      advancement flap, it is also possible to use a dog-ear on the nasolabial region
      for any alar defects. Nine patients were treated using this procedure. The
      technique is very reliable (no complications such as congestion and skin necrosis
      in our series) and is easy to perform. One patient had palpebral ectropion after
      the operation and underwent secondary repair. In this series, defects measuring
      45 x 30 mm in maximum diameter and including the nasal dorsum, nasal tip, ala,
      and cheek were treated.

PMID- 11335801
TI  - The fate of free flaps used to reconstruct defects in recurrent head and neck
      cancers.
AB  - The purpose of this study was to assess free-flap viability in patients treated
      for recurrent head and neck cancers. A 10-year retrospective review identified
      121 patients who had had prior head and neck cancers extirpated for cure, who
      subsequently presented with documented recurrent cancers that were removed, and
      who then underwent reconstruction with free flaps. The charts of these patients
      were reviewed for patient demographics, tumor types, location, flaps used for
      reconstruction, size of area requiring reconstruction, length of operation,
      previous radiation, and all postoperative morbidity and mortality. The time to
      recurrence ranged from 21/2 months to 21 years. The majority of tumors treated
      were squamous cell carcinomas (n = 82). Most of them were located intraorally (n
      = 75). Radiation therapy had been delivered to 88 patients before their free-flap
      reconstructions. In this series, 31 percent of all patients required additional
      surgery for complications, 14 percent of free flaps were lost, and 4 percent of
      patients died within 30 days of their operation. The significant findings were
      that a flap that was >4 cm in diameter was related to flap loss (p = 0.03 by the
      chi2 method) and that flap loss was related to operative times greater than 11
      hours (p = 0.03 by the chi2 method). It was concluded that recurrent head and
      neck cancers with large postextirpation defects that required prolonged operative
      times yielded a significantly high tendency toward flap failure.

PMID- 11335803
TI  - Prospective comparison of panoramic tomography (zonography) and helical computed
      tomography in the diagnosis and operative management of mandibular fractures.
AB  - This prospective study compared the sensitivity of panoramic tomography
      (zonography) and helical computed tomography (CT) in diagnosing 73 mandibular
      fractures in 42 consecutive patients and correlated the results with known
      surgical findings. The purpose of the study was to determine the optimal
      radiologic examination for the diagnosis and operative management of mandibular
      fractures. The attending surgeons' interpretations of panoramic tomograms and
      helical CT images in the axial plane were compared with the patients' known
      surgical findings. A series of questions assessed the relative contribution of
      these two radiologic examinations in formulating an optimal operative plan for
      each patient. In the 42 patients studied, the sensitivity of helical CT was 100
      percent in diagnosing mandibular fractures; this compared with 86 percent (36 of
      42) for panoramic tomography, in which significantly more fractures were missed
      (p = 0.0412). In the six patients with fractures not visualized, the operative
      management was altered because of the new fracture visualized on helical CT. Of
      the seven missed fractures, six were in the posterior portion of the mandible.
      Comparing fracture detection by region, seven fractures found on helical CT were
      not visualized on panoramic tomography. Helical CT improved the understanding of
      the nature of mandibular fractures by providing additional information regarding
      fracture displacement and comminution and by locating injuries missed using
      panoramic tomography. This study suggests that helical CT alone may be more
      diagnostic than panoramic tomography alone in evaluating mandibular fractures.
      Helical CT sufficiently demonstrated details of fractures in 41 of 42 patients;
      in one patient, the nature of a dental root fracture was better delineated by
      panoramic tomography.

PMID- 11335804
TI  - Treatment of poikiloderma of Civatte on the neck with an intense pulsed light
      source.
AB  - Effective treatment of poikiloderma of Civatte is difficult. The ideal treatment
      combines elimination of both the vascular and pigmented components
      simultaneously. Treatment with a broad-spectrum noncoherent intense pulsed light
      source delivers multiple wavelengths with software-controlled pulse durations and
      sequencing that permit treatment of both vascular and pigmented lesions
      simultaneously. The objective of this study was to determine the response and
      side effects of treating this condition with intense pulsed light. In the study,
      66 patients with typical changes of poikiloderma of Civatte on the neck were
      treated with intense pulsed light at various settings every 4 weeks until the
      desired improvement occurred. A 50 to 75 percent improvement in the extent of
      telangiectasias and hyperpigmentation was observed after an average of 2.8
      treatments. The incidence of hypopigmentation was 5 percent. It was concluded
      that intense pulsed light is an effective mode of therapy for poikiloderma of
      Civatte. It seems to offer a reduction in both pigmentation and telangiectasia
      associated erythema, with minimal side effects.

PMID- 11335805
TI  - Extended V-Y latissimus dorsi musculocutaneous flap for anterior chest wall
      reconstruction.
AB  - Patients presenting advanced breast tumors are usually subject to major
      resections of the anterior chest wall tissue. Flaps taken from the abdominal
      wall, such as the TRAM, the external oblique flap, and the thoracoabdominal flap
      are frequently used for closure of this type of lesion. In this study, a
      different shape was planned for the skin island from the latissimus dorsi
      musculocutaneous flap with primary closure in V-Y for the correction of major
      lesions in the anterior chest wall after mastectomies occasioned by advanced
      breast cancer. The technique was used on eight female patients, between November
      of 1998 and July of 1999, victims of advanced breast cancer, who had been
      submitted to radical mastectomies with major resections of the cutaneous
      tegument. It was possible to make primary closure of lesions in the anterior
      chest wall, the preoperative areas of which varied between 15 x 15 and 29 x 14 cm
      (vertical x horizontal). This technical variant permitted use of the flap without
      the need to create tunnels for its advancement and rotation. It also proved to be
      easy to perform and presented a low morbidity rate, with three patients
      presenting minor complications that did not require correction through any
      further surgical intervention. Closure was obtained in the donor and recipient
      sites without the use of skin grafts or other more major procedures. According to
      the authors, this procedure is a viable alternative in repairing large defects in
      the anterior chest wall.

PMID- 11335807
TI  - Breast implants and cancer: causation, delayed detection, and survival.
AB  - Concern for many women with breast implants has been focused on three topics:
      cancer (both breast and other cancers), delayed detection of breast cancer, and
      increased breast cancer recurrence or decreased length of survival. In this
      study, a qualitative review of the literature on these subjects was conducted,
      coupled with a meta-analysis of the risk for breast cancer or other cancers
      (excluding that of the breast). Researchers have consistently found no persuasive
      evidence of a causal association between breast implants and any type of cancer.
      The meta-analysis results obtained by combining the epidemiology studies support
      the overall conclusion that breast implants do not pose any additional risk for
      breast cancer (relative risk, 0.72; 95% confidence interval, 0.61 to 0.85) or for
      other cancers (relative risk, 1.03; 95% confidence interval, 0.87 to 1.24). This
      analysis suggests that breast implants may confer a protective effect against
      breast cancer. Women with implants should be reassured by the consistency of
      scientific studies which have uniformly determined that, compared with women
      without implants, they are not at increased risk for cancer, are not diagnosed
      with later-stage breast malignancies, are not at increased risk for breast cancer
      recurrence, and do not have a decreased length of survival.

PMID- 11335808
TI  - Immediate breast reconstruction with saline-filled implants: no interference with
      the oncologic outcome?
AB  - The possible adverse effects on cancer control due to immediate breast
      reconstruction have been addressed recently for both silicone-filled implants and
      flap reconstruction. To evaluate those possible effects after immediate breast
      reconstruction with saline-filled implants, 49 patients reconstructed with saline
      filled breast implants at the Jules Bordet Cancer Institute were studied.
      Selection was only based on the possibility to find a matched patient. These
      patients were matched with a control group of 49 matched women with breast cancer
      treated in the same center by mastectomy without any type of breast
      reconstruction. The two groups were comparable according to age at diagnosis
      (within 3 years), year of diagnosis (same year), stage of the tumor, histology,
      and nodal status. The only difference between the two groups was that radiation
      therapy was applied to some of the patients who were not reconstructed (due to
      tumor location). The results show, in terms of local recurrences, distant
      metastasis, and deaths, no significant difference between the two groups, even
      for the irradiated patients, within a mean follow-up period of 72 months (range,
      24 to 108) months.

PMID- 11335809
TI  - Comparison of cost for DIEP and free TRAM flap breast reconstructions.
AB  - A recent article by Kaplan and Allen suggested that deep inferior epigastric
      perforator (DIEP) flap breast reconstruction was less expensive than
      reconstruction performed with free transverse rectus abdominis musculocutaneous
      (TRAM) flaps. To test that hypothesis, a series of patients who had undergone
      unilateral breast-mound reconstruction by the first author using DIEP or free
      TRAM flaps between November 1, 1996, and March 30, 2000, were reviewed. Bilateral
      reconstructions and reconstructions performed by other surgeons in the department
      were excluded to eliminate all variables except the choice of flap. All hours in
      the operating room and days in the hospital until discharge were included. Early
      readmissions for the treatment of complications were included, as were the costs
      of the mastectomy in the case of immediate reconstructions, but late revisions
      and nipple reconstructions were not. The totals were then converted into resource
      costs in 1999 dollars, and the DIEP and free TRAM flap groups compared. There
      were 21 DIEP flaps and 24 free TRAM flaps in the series. In this series, there
      was no significant difference between the cost of DIEP and free TRAM flap breast
      reconstruction.

PMID- 11335811
TI  - Clinical outcome following nerve allograft transplantation.
AB  - The clinical outcome of seven patients who underwent reconstruction of long upper
      and lower-extremity peripheral nerve gaps with interposition peripheral nerve
      allografts is reported. Patients were selected for transplantation when the nerve
      gaps exceeded the length that could be reconstructed with available autograft
      tissue. Before transplantation, cadaveric allografts were harvested and preserved
      for 7 days in University of Wisconsin Cold Storage Solution at 5 degrees C. In
      the interim, patients were started on an immunosuppressive regimen consisting of
      either cyclosporin A or tacrolimus (FK506), azathioprine, and prednisone.
      Immunosuppression was discontinued 6 months after regeneration across the
      allograft(s) was evident. Six patients demonstrated return of motor function and
      sensation in the affected limb, and one patient experienced rejection of the
      allograft secondary to subtherapeutic immunosuppression. In addition to providing
      the ability to restore nerve continuity in severe extremity injuries, successful
      nerve allografting protocols have direct applicability to composite tissue
      transplantation.

PMID- 11335812
TI  - Osteomuscular latissimus dorsi scapula flap to repair chronic, posttraumatic
      osteomyelitis of the lower leg.
AB  - Fractures of the lower leg with soft-tissue loss may be complicated by
      osteomyelitis. Many treatment plans offered in the past have included the use of
      vascularized bone, but the soft tissue that accompanied the bone was sometimes
      less than ideal in quality as well as quantity. This study presents a one-step
      method for the surgical treatment of chronic, posttraumatic osteomyelitis that
      includes (1) radical debridement of the area affected by osteomyelitis, (2) use
      of revascularized bone for stabilization of the affected area, and (3) well
      vascularized soft-tissue cover for the defect. The use of an osteomuscular
      latissimus dorsi scapula flap is described and illustrated by descriptions of
      five operations performed by the authors' department in Salzburg, Austria. The
      resultant healing of the bone was comparable to the primary healing of a
      fracture.

PMID- 11335814
TI  - Free-tissue transfer for limb salvage in Purpura fulminans.
AB  - A series of 13 patients is described to demonstrate the experience of the authors
      with free-tissue transfer for limb salvage in patients with purpura fulminans. A
      total of seven free-flap procedures were performed, with a loss of flap in one
      patient. The flaps were used for lower-extremity salvage in six patients and for
      upper-extremity salvage in one. Purpura fulminans is a devastating illness caused
      by endotoxin-producing bacteria such as meningococcus and pneumococcus. Clotting
      derangements and systemic vasculitis often lead to widespread tissue necrosis in
      the extremities. Local tissue is usually not available to cover vital structures
      in these complex wounds. In these situations, free-tissue transfer is necessary
      to achieve limb salvage. Microsurgical reconstruction in patients with purpura
      fulminans is a formidable challenge. Because of high platelet counts and systemic
      vasculitis, successful microvascular anastomosis is difficult. Abnormally high
      platelet counts persist well into the subacute and chronic phases of the illness.
      Pretreatment with antiplatelet agents before microvascular surgery may be
      beneficial. The systemic nature of the vascular injury does not permit
      microvascular anastomosis to be performed outside the "zone of injury." Extensive
      vascular exposure, even at a great distance from the wound, does not reveal a
      disease-free vessel. The friable intima is difficult to manage with a standard
      end-to-side anastomosis, but conversion to end-to-end anastomosis may salvage
      free-tissue transfers in cases in which intimal damage is too severe to sustain a
      patent anastomosis. Patients often have peripheral neuropathies caused by the
      underlying disease; however, this resolves with time and is not a
      contraindication to limb salvage.

PMID- 11335815
TI  - The distally pedicled peroneus brevis muscle flap: a new flap for the lower leg.
AB  - Defects of the skin and soft tissue in the region of the lateral malleolus of the
      ankle and the Achilles tendon, resulting in exposed bone, tendons, or
      osteosynthetic material, cannot be covered with free skin transplants. Local or
      free flaps must be employed. The authors present the construction of a peroneus
      brevis muscle flap with a distal pedicle as a useful alternative. Between 1993
      and 1999, distal pedicled peroneus brevis muscle flaps were used in 19 patients
      with various types of defects. During construction of the flap, both the long
      peroneal muscle and the peroneal artery remained intact. In the region of the
      distal third of the fibula, consistently arranged branches run from the artery
      into the muscle, and these form the distal pedicle. The proximal portion of the
      muscle can be transposed distally and easily extends to the tip of the fibula and
      the attachment of the Achilles tendon to the calcaneus. Primary healing occurred
      in 16 patients undergoing flap construction. Donor-site morbidity was mostly
      limited to the donor-site scar. The distally pedicled peroneus brevis muscle flap
      is a reliable means for covering defects in the lower leg. This form of muscle
      flap has not yet been described in the known literature. In the authors' opinion,
      this flap constitutes a logical and valuable extension of local flap procedures
      for plastic surgery in the distal leg region.

PMID- 11335816
TI  - Ulnar polydactyly.
AB  - A retrospective review of 148 patients with ulnar polydactyly was conducted to
      analyze the types, patterns of involvement, associated anomalies, treatments, and
      outcomes of this malformation. The hands only were involved in 123 patients, both
      hands and feet in 20 patients, and five patients had mixed radial and ulnar
      polydactyly. Ulnar polydactyly was more prevalent among males. Among African
      Americans, the condition was often bilateral. When unilateral, ulnar polydactyly
      occurred more often on the left side. The racial distribution was 103 African
      Americans (70 percent), 37 Caucasians (25 percent), four Native Americans, three
      Latin Americans, and one Asian. Five types were encountered: type I cutaneous
      nubbin, type II pedunculated digit, type III articulating digit with fifth
      metacarpal, type IV fully developed digit with sixth metacarpal, and type V
      polysyndactyly. The distribution of types in order of frequency was type II, III,
      V, I, and IV. Types I and II ulnar polydactyly combined were more prevalent (82
      percent) than types III, IV, and V (18 percent). Types I and II were more common
      among African Americans. Types III, IV, and V ulnar polydactyly occurred more
      frequently among Caucasians, but these were slightly less prevalent than types I
      and II in this racial group. Five patients were syndromic; four were Caucasians,
      and one Asian. Most cases of ulnar polydactyly of the hand were treated by
      ligation (71 percent) in the nursery, whereas polydactyly of the foot was more
      often referred to a specialist to be treated by surgical ablation (92 percent).
      Treatment complications occurred more frequently in the hands than in the feet.
      The complication rate after ligation of ulnar polydactyly of the hand was 23.5
      percent. The two main complications were tender or unacceptable nubbins and
      infections.

PMID- 11335818
TI  - Correction of first web space deficiency in congenital deformities of the hand
      with the pseudokite flap.
AB  - The authors describe a new flap to enlarge or create a first web in patients with
      congenital deficiencies of the hand. This lozenge-shaped flap is harvested from
      the dorsoradial aspect of the index finger based on a narrow proximal skin bridge
      protecting its axial vascularization. A dorsal skin graft of the donor site is
      avoided by closure using a rhomboid flap. Procedures in 16 patients were
      performed and reviewed; the only complication was insertion of a small split
      thickness graft in five patients to avoid tension at the metacarpophalangeal
      joint level. The flap lengthened the web fold an average of 3.2 cm without
      "pseudolengthening" the thumb.

PMID- 11335819
TI  - Comparison of carpal canal pressure in paraplegic and nonparaplegic subjects:
      clinical implications.
AB  - The purpose of this study was to evaluate the pressure within the carpal tunnel
      that was generated with certain tasks in paraplegic versus nonparaplegic
      subjects. Four groups of subjects were evaluated: 10 wrists in six paraplegic
      subjects with carpal tunnel syndrome, 11 wrists in six paraplegics without the
      syndrome, 12 wrists in nine nonparaplegics with the syndrome, and 17 wrists in 11
      nonparaplegics without the syndrome. Carpal canal pressures were measured in the
      wrists in three positions (neutral, 45-degree flexion, 45-degree extension) and
      during two dynamic tasks [wheelchair propulsion and RAISE (relief of anatomic
      ischial skin embarrassment) maneuver]. External force resistors were placed over
      the carpal canal and correlated with internal tunnel pressures. At each wrist
      position, paraplegics with carpal tunnel syndrome consistently had higher carpal
      canal pressure than did the other groups at the corresponding wrist position;
      statistical significance was evident with regard to the neutral wrist position (p
      < 0.05). Within each group of subjects, wrist extension and wrist flexion
      produced a statistically significant increase in carpal canal pressure (p <
      0.05), compared with the neutral wrist position. Dynamic tasks (wheelchair
      propulsion and the RAISE maneuver) significantly elevated the carpal canal
      pressure in paraplegics with carpal tunnel syndrome, compared with the other
      groups (p < 0.05). Lastly, there is a linear positive correlation between carpal
      canal pressure and external force resistance.

PMID- 11335821
TI  - Flap surgery to cover olecranon pressure ulcers in spinal cord injury patients.
AB  - In the quadriplegic patient, the periolecranon region is subjected to continuous
      and permanent mechanical shearing and pressure forces. As the sensation of this
      region is partially impaired secondary to the level of the spinal cord injury,
      this anatomical area is prone to develop bursitis and then a chronic open
      draining wound. This type of wound is refractory to conservative measures.
      Surgical closure of this functional area can represent a challenge to the plastic
      and reconstructive surgeon because not all of the surgical options available are
      suitable for spinal cord injury patients. Therefore, we describe our clinical
      experience, which consists of seven patients with traumatic complete quadriplegia
      treated between 1989 and 1998 (all patients were male) who presented with an open
      olecranon ulcer, septic bursitis, or aseptic bursitis, and who underwent surgical
      closure by direct closure, local arm fasciocutaneous flap, or cross-chest flap to
      cover the periolecranon soft-tissue defects. The follow-up period ranged from 3
      months to 8 years (mean, 44 months). All types of flaps achieved wound closure
      without losing range of motion at the elbow; however, at 10 to 12 months after
      surgery, an olecranon pressure ulcer or septic bursitis recurred in three of
      seven patients. These three patients required surgical revision. The local
      fasciocutaneous rotational flap was found to be effective for closing
      periolecranon soft-tissue defects and can be reused in instances of recurrence.
      Patient education is essential to prevent re-ulceration in that functional area
      in the spinal cord injury patient.

PMID- 11335822
TI  - Tolerance to limb tissue allografts between swine matched for major
      histocompatibility complex antigens.
AB  - Transplantation of limb tissue allografts would greatly expand the realm of
      reconstructive surgery. However, the toxicity of chronic immunosuppression has
      adversely tilted the risk-benefit balance for clinical transplant. In this study,
      a procedure was sought to achieve host tolerance to limb tissue allografts
      through matching of the major histocompatibility complex (MHC) antigens between
      donor and host swine using only a 12-day course of cyclosporine. Massachusetts
      General Hospital (MGH) miniature swine were used as a large animal model with
      defined MHC, and musculoskeletal grafts from the donor hind limb were
      transplanted heterotopically to the recipient femoral vessels. Allografts from
      MHC-mismatched donors treated with cyclosporine (n = 4) were rejected in less
      than 6 weeks by gross inspection and histologic sections. Allografts from MHC
      matched, minor antigen mismatched donors not treated with cyclosporine (n = 4)
      were rejected between 9 and 12 weeks. Allografts from similarly matched donors
      treated with 12 days of cyclosporine (n = 7) showed no evidence of rejection
      until sacrifice between 25 and 47 weeks. Thus allograft tolerance was achieved
      between MHC-matched swine using a limited course of cyclosporine. Demonstration
      of limb tissue allograft survival in a large animal model without long-term
      immunosuppression represents an important step toward clinical transplantation.

PMID- 11335824
TI  - Pseudoangiomatous tumor of the breast.

PMID- 11335825
TI  - "Reverse turnover" transfer of a latissimus dorsi muscle flap to a large lumbar
      defect.

PMID- 11335826
TI  - Reconstruction of achilles tendon and skin defects using peroneal
      cutaneotendinous flaps.

PMID- 11335827
TI  - A potential murine model for flap-related investigations.

PMID- 11335828
TI  - Progress toward understanding vascular malformations.

PMID- 11335832
TI  - Getting a life.

PMID- 11335829
TI  - Upper extremity microsurgery.
AB  - LEARNING OBJECTIVES: After studying this article, the participant should be able
      to: 1. Understand the indications for free flap coverage of the upper extremity.
      2. Know the advantages and disadvantages of the flaps discussed. 3. Have a basic
      understanding of the anatomy of the flaps discussed. 4. Have a variety of options
      for free tissue transfer.The application of microsurgical tissue transfer to
      reconstruction of the upper extremity allows repair of significant bone and soft
      tissue defects. Through the years the approach has changed from one of simply
      getting the wound covered to primary reconstruction to preserve or regain
      function. A wide variety of free flaps offers the potential to reconstruct nearly
      any defect of the arm and hand. Vascularized bone transfer can be utilized to
      repair large bony defects, while innervated free muscle transfer can replace
      missing muscle function. The total array of flaps and their indications is beyond
      the scope of a single discussion, but this article focuses on a few flaps that
      have found application for coverage and functional restoration in the hand and
      upper extremity.

PMID- 11335833
TI  - Surgery of the superficial musculoaponeurotic system: principles of release,
      vectors, and fixation.
AB  - The SMAS was described more than 25 years ago, yet its full potential in face
      lift surgery has become appreciated only more recently. A reappraisal of the
      various aspects of SMAS surgery is now appropriate. These include aspects of its
      release from the deep fascia, the several considerations underlying the vectors
      of flap redistribution, and the rationale underlying the methods of flap
      fixation. These are unique, compared with the traditional considerations in
      subcutaneous face lifts and en bloc subperiosteal lifts.

PMID- 11335837
TI  - The zones of adherence: role in minimizing and preventing contour deformities in
      liposuction.
AB  - True body sculpting demands a three-dimensional artistic understanding of the
      anatomic and surgical adipose layers of the central trunk when performing
      circumferential liposuction. This is essential in preventing complications from
      both ultrasound-assisted and suction-assisted lipoplasty. The authors describe
      five zones of adherence that should be avoided to prevent contour deformities in
      the central trunk area when performing circumferential liposuction. The anatomy
      of the subcutaneous tissue of these five anatomic zones is reviewed and
      correlated radiographically with magnetic resonance imaging studies. Aesthetic
      and technical considerations required to properly liposculpt the central trunk
      are demonstrated by case analysis of primary and secon-dary liposuction patients.
      These cases also delineate how to prevent and/or minimize deformities after
      liposuction.

PMID- 11335838
TI  - Deep venous thrombosis and pulmonary embolus after face lift: a study of
      incidence and prophylaxis.
AB  - Deep venous thrombosis and pulmonary embolus are known risks of surgery. However,
      the incidence of these conditions in face lift is unknown. In this study, the
      incidence of deep venous thrombosis/pulmonary embolus after face lift is studied
      and factors associated with thromboembolic complications are evaluated. One-third
      of the active members of the American Society for Aesthetic Plastic Surgery were
      randomly selected. Participating surgeons completed a one-page survey providing
      information on face-lift procedures during a 12-month study period. A response
      rate of 80 percent was achieved, with 273 of the 342 surgeons responding to the
      survey. A total of 9937 face-lift procedures were reported in the 1-year study
      period. There were 35 patients with deep venous thrombosis (0.35 percent), 14
      patients with pulmonary embolus (0.14 percent), and 1 patient death in the
      series. Although 43.5 percent of patients underwent face lift under general
      anesthesia, 83.7 percent of deep venous thrombosis/pulmonary embolus events
      occurred with general anesthesia. For prophylaxis for deep venous
      thrombosis/pulmonary embolus, 19.7 percent of the surgeons used intermittent
      compression devices, 19.6 percent used thromboembolic disease hose or Ace wraps,
      and 60.7 percent used no prophylaxis. Of patients developing deep venous
      thrombosis/pulmonary embolus, 4.1 percent were treated prophylactically with
      intermittent compression devices, 36.7 percent with thromboembolic disease
      hose/Ace wraps, and 59.2 percent with no prophylaxis. It was found that deep
      venous thrombosis/pulmonary embolus after face lift is a measurable complication
      experienced by one of nine surgeons surveyed. Deep venous thrombosis/pulmonary
      embolus is more likely to occur when the procedure is performed under general
      anesthesia. The majority of plastic surgeons surveyed used no prophylaxis for
      deep venous thrombosis when performing face-lift procedures. Intermittent
      compression devices were associated with significantly fewer thromboembolic
      complications, whereas Ace wrap/thromboembolic disease hose afforded no
      protection against deep venous thrombosis/pulmonary embolus when used alone. In
      conclusion, aesthetic surgeons should consider adopting intermittent compression
      devices when performing face lift under general anesthesia.

PMID- 11335840
TI  - The long-term durability of plication of the anterior rectus sheath assessed by
      ultrasonography.
AB  - The purpose of this study was to assess the long-term durability of a standard
      vertical plication of the anterior rectus sheath. For this purpose, 70 women who
      had undergone this procedure as part of an abdominoplasty were sent a
      questionnaire, their records were studied, and they were invited back to the
      clinic for an examination using ultrasound. A total of 63 patients returned the
      questionnaire, and 40 were willing to attend a follow-up consultation and
      ultrasound investigation. The presence of rectus diastasis was assessed by
      ultrasound (a real time scanner with a 7.5-MHz linear probe). The study showed
      that after a follow-up of 32 to 109 months (mean, 64 months), standard plication
      of the abdominal wall with absorbable material led to residual or recurrent
      diastasis in 40 percent of the patients. It also confirmed that vertical
      plication only is not enough to improve the waistline and may eventually lead to
      epigastric bulging.

PMID- 11335841
TI  - Infraorbital rim augmentation.
AB  - In patients with recessive infraorbital rims, alloplastic augmentation of the
      infraorbital rims makes the eyes appear less prominent and improves appearance.
      Ten patients (seven women and three men) with an average age of 30 years (range,
      23 to 45 years) underwent augmentation of the infraorbital rim with alloplastic
      implants over a 9-year period. With an average follow-up of 3 years (range, 6
      months to 6 years), reconstructions have remained stable and satisfactory, with
      no incidence of infection, infraorbital nerve damage, or palpebral fissure
      distortion. One patient underwent additional surgery to correct contour
      irregularities, and one patient requested implant removal 1 month after surgery.

PMID- 11335843
TI  - The suborbicularis oculi fat pad: an anatomic and clinical study.

PMID- 11335845
TI  - Surgical training.

PMID- 11335849
TI  - Medicare physician payment for practice expense: is it refined? Part 1. Office
      visit reevaluations.
AB  - OBJECTIVES: To analyze the Medicare physician fee schedule practice expense
      payments, focusing on the 2001 changes for office visits, and to estimate the
      impact of these changes. METHODS: We analyzed the source data posted on the
      Health Care Financing Administration Web site to quantitate the changes in the
      office visit payments, the impact on Medicare payments by specialty, and the
      details of the office visit direct cost input changes. RESULTS: The 2001 office
      visit changes result in a redistribution of $600 million per year in Medicare
      payments away from cognitive services. Specialties that depend on such services
      for major portions of their incomes are adversely affected. Family physicians
      lose about $65 million per year and internists about $74 million per year in
      Medicare income alone. CONCLUSIONS: This substantial physician income
      redistribution was made with little advance notice, raising questions about its
      lawfulness. The volume of data needed to understand the practice expense changes
      and the rapidity with which changes are implemented highlights the usefulness of
      the Internet in disseminating information about these activities that critically
      affect physician practice.

PMID- 11335851
TI  - In response - case control study on radiology work, medical X-ray investigations
      and use of cellular phones as risk factors for brain tumors.

PMID- 11335854
TI  - When criminals are shot -- a response.

PMID- 11335855
TI  - Computers, doctors, and toilet training.

PMID- 11335856
TI  - Autopsies.

PMID- 11335860
TI  - From the Art Director's Desk.

PMID- 11335858
TI  - Words that are not spoken: an inside look at the African AIDS crisis.

PMID- 11335861
TI  - From Andrew Herxheimer's Desk. FROM THE LAND OF THE SICK: Doctors as patients.

PMID- 11335862
TI  - Effect of estradiol 17-beta on LH subunits and prolactin mRNAs expression in the
      pituitary of old female rats.
AB  - OBJECTIVES: The aim of the study was to examine susceptibility of the pituitary
      gland to estrogenic impulse in old, noncycling rats by measurement of steady
      state level of mRNAs encoding LH subunits a and b and mRNA for PRL. METHODS: 22
      month-old rats were ovariectomized and after one week they were subcutaneously
      implanted with silastic tubing filled with oil or with estradiol 17-beta.
      Pituitary alpha, LHbeta and PRL mRNAs content and serum LH and PRL concentration
      was determined. RESULTS: The effect of E (2)treatment was manifested by the
      significant increase in the weight of the uterus and pituitary gland as well as
      by elevation of total pituitary RNA (109%, 60% and 78%, respectively; p<0.001).
      No significant changes (p>0.05) in serum LH concentration were observed, while
      levels of mRNAs encoding alpha and LH-beta subunits were lowered by 54% (p<0.05)
      and 96% (p<0.01), respectively, in the rats subjected to E(2) stimuli. No direct
      correlation between synthesis and release of LH in E(2) treated old rats was
      observed. The blood PRL concentration and the pituitary level of PRL mRNA
      increased up to 2,000% and 1,300%, respectively (p<0.001). Spontaneous pituitary
      adenoma was observed in about 30% of the rats, irrespective of treatment.
      CONCLUSIONS: These data show that in old rats estrogenic stimulus can effectively
      diminish both pituitary LH subunits mRNAs as well as stimulate pituitary PRL mRNA
      level indicating that the E(2)-dependent processes involved in the regulation of
      corresponding genes are still functional.

PMID- 11335863
TI  - Melatonin concentrations in patients with large goiter before and after surgery.
AB  - OBJECTIVES: Surgical removal of a very large goiter may traumatize adjacent
      anatomical structures. The manipulations that involve superior cervical ganglia
      may alter melatonin secretion. To test this hypothesis we decided to study
      diurnal serum melatonin profiles in patients with a very large goiter before and
      after the surgery. MATERIAL AND METHODS:The study was performed on 10 women (mean
      age-46.5+/-1.6 years; mean+/-SEM; range 39-54 years) with very large non-toxic
      nodular goiter (mean thyroid volume-125.8+/-25.9 cm (3); mean+/-SEM; range 82.6
      326.7 cm(3)). Diurnal serum melatonin profiles were estimated two days before the
      operation and 10 days after the surgery. Blood samples were collected at 08:00,
      12:00, 16:00, 20:00, 22:00, 24:00, 02:00, 04:00, 06:00 and 08:00 h. Melatonin
      concentration was measured using RIA kit. RESULTS: Nocturnal serum melatonin
      concentrations (at 24, 02, and 04 hours) were significantly higher after the
      surgery than before the operation. CONCLUSIONS: Very large goiter may compress
      the superior cervical ganglia altering indirectly the melatonin synthesis. It
      cannot be excluded, however, that the presence of the large goiter in some other
      way affects melatonin secretion.

PMID- 11335864
TI  - Effect of aproteic diet and fasting on insulin, pancreatic noradrenaline and
      luteinizing hormone. Changes after 24-hour refeeding.
AB  - OBJECTIVE AND DESIGN: the objective of this study performed in adult male rats
      was to determine the alteration in glycemic, insulin and gonadotrophin
      luteinizing hormone secretion, and noradrenaline pancreatic concentration caused
      by fasting (F) and aproteic diet (Ap) during 7 and 21 days respectively, as well
      as the recovery after 24-hour refeeding with control diet (Co). RESULTS: a
      significant decrease in glycemic levels was only achieved through fasting (F: 86
      +/- 5.1 mg %), when compared with controls (Co: 107 +/- 5 mg %). In spite of the
      high levels of carbohydrates (89%) present in the aproteic diet, the animals fed
      with this diet showed no differences in glycemic levels (Ap: 120.3 +/- 12.2 mg
      %), compared with controls. As a result of fasting and aproteic diet, there was a
      significant decrease in insulin (F: 8.67 +/- 1.36; Ap: 5.7 +/- 0.67; Co: 31 +/-
      3.4 uU/ml) and LH levels (F: 10.175 +/- 1.74; Ap: 13.7 +/- 4; Co: 29.83 +/- 4.91
      ng/ml). The refed recovered insulin (FR: 50.57 +/- 6.63; ApR: 43.5 +/- 6.85
      uU/ml), but not LH levels (FR: 14.25 +/- 3.54; ApR: 13.03 +/- 4.25 ng/ml). A
      significant increase was observed in the pancreatic noradrenaline concentration
      (P<0.001) of rats receiving aproteic diet (889.9 +/- 34.65 ng/mg tissue) and
      fasting during 7 days (827.5 +/- 55.7 ng/mg tissue), compared with controls
      (531.1 +/- 48.6 ng/mg tissue). CONCLUSIONS: fasting and aproteic diets altered
      gonadal and metabolic control. When returning to a normal nutritional condition,
      only the metabolic control, not the reproductive function, could be recovered in
      the first 24 hours of refeeding. Malnutrition-induced hypoinsulinemia would be
      caused by an increase in a specific noradrenergic tone.

PMID- 11335865
TI  - Neither gynecomastia nor galactorrhea is a common side effect of neuroleptics in
      male patients.
AB  - OBJECTIVE: Gynecomastia is known to be a side effect of neuroleptics. The authors
      investigated the prevalence of gynecomastia and galactorrhea in a group of
      regularly neuroleptic-treated male patients. METHODS: Gynecomastia was defined as
      a palpable, discrete button of firm subareolar tissue measuring at least 2 cm in
      diameter. The subjects were 100 male patients who were taking neuroleptic
      treatment regularly. Each patient gave informed consent for the research involved
      in this study. RESULTS: (1) Palpable gynecomastia was present in 2% of the
      patient group, but not at all in the normal group. (2) Galactorrhea was not
      present in either patient or normal group. (3) The mean level of the serum
      prolactin in the group of patients without gynecomastia (n = 53) was
      significantly higher than that in the normal group (n = 35), but there was no
      significant difference in blood luteinizing hormone, follicle-stimulating
      hormone, testosterone (T), estradiol (E(2)) or T/E(2) ratio between the groups.
      (4) The mean level of the T/E(2) ratio in the patients with gynecomastia tended
      to be higher than that in the group of patients without gynecomastia.
      CONCLUSIONS: Overall, these results seem to indicate that (i) gynecomastia is not
      common in the Japanese population, and (ii) in male patients neither palpable
      gynecomastia nor galactorrhea is a common side effect of neuroleptics. To clarify
      the relation between gynecomastia and neuroleptic treatment, large prospective
      studies are required.

PMID- 11335866
TI  - Thymidine kinase and adenosine kinase activities in homogenates of thyroid lobes
      in hemithyroidectomized rats; effects of melatonin in vitro.
AB  - OBJECTIVES: Thymidine kinase (TK, EC 2.7.1.21) is a part of the pyrimidine
      salvage pathway, involved in DNA synthesis. In turn, adenosine kinase (AK, EC
      2.7.1.20) functions as a part of the purine metabolic pathway, involved in DNA
      synthesis. Melatonin (Mel) is an indoleamine which is known to inhibit growth
      processes in the thyroid gland and also in other endocrine and non-endocrine
      tissues. The aim of our study was to examine TK and AK activities in homogenates
      of the rat thyroid lobes remaining after contralateral hemithyroidectomy
      (hemiTx); additionally, incubations with Mel (10(-6), 10(-9), and 10(-12) M) were
      performed. METHODS: The experiment was performed on young male Wistar rats (6
      week old). The enzyme activities were measured by ascending chromatography and
      expressed as the amounts of radioactive reaction products of the phosphorylation
      of dThd (for TK) and of dAdo (for AK). RESULTS: 1. HemiTx increased TK activity
      in homogenates of the remaining thyroid lobe; 2. Mel increased TK activity in all
      the groups (intact, sham-operated- and hemiTx-rats), except for the
      concentrations of 10(-9) and 10(-12) M in the hemiTx-rats, in which the
      increasing effects of Mel on TK activity reached the borderline statistical
      significance only; 3. Mel increased the AK activity in intact and in shamTx
      animals; 4. No statistically significant changes were found in AK activity
      following Mel in vitro in the incubated remaining thyroid lobes, collected from
      hemiTx-rats.

PMID- 11335867
TI  - Melatonin protects against oxidative stress induced by the kidney carcinogen
      KBrO(3).
AB  - OBJECTIVES: Free radical scavengers can protect against the genotoxicity induced
      by chemical carcinogens by decreasing oxidative stress. The protective effect of
      the antioxidant melatonin was studied in the kidney and liver of rats treated
      with the kidney-specific carcinogen potassium bromate (KBrO(3)). The major
      endpoint of oxidative damage measured in this report was lipid peroxidation.
      METHODS: Four groups of male rats (controls, melatonin-injected [10 mg/kg x4],
      KBrO(3)-injected [100 mg/kg], and melatonin+-KBrO(3)) were used in the current
      study. The concentrations of malondialdehyde (MDA) were assayed as an index of
      oxidatively damaged lipid in the kidney and liver. RESULTS: Twenty-four hours
      after KBrO(3) administration, MDA levels were significantly increased in the
      kidney while the increase in the liver was not statistically significant compared
      to levels in control rats. The percentage increases in lipid peroxidation
      products were 32.8% and 12.6% for the kidney and liver, respectively. In rats
      given melatonin 30 minutes before KBrO(3), and three more times after KBrO(3)
      (i.e., every 6 hours), the increase in MDA levels was reduced in the kidney.
      Histopathological examination demonstrated marked changes in the structure of the
      kidney and slight changes in the liver. In the kidney, microscopic examination
      revealed atypical tubules, atypical hyperplasia, hyaline droplet degeneration,
      necrotic changes and stratified squamous cell metaplasia. Again, melatonin
      treatment inhibited the tissue damage associated with KBrO(3) administration.
      CONCLUSION: These results show that melatonin as an antioxidant and free radical
      scavenger can prevent oxidative stress induced by the carcinogen KBrO(3).

PMID- 11335868
TI  - Birthweight - is it linked to minor illness in adulthood? 
AB  - OBJECTIVE: The Barker's hypothesis states that poor nutrition in vitro is linked
      to low birthweight and major illness, in particular cardiovascular disease, in
      later life. Reported here is an investigation to establish links with birthweight
      and minor illness. METHODS: 78 participants whose birthweight ranged from 1.93 kg
      to 4.88 kg with a mean to 3.31 kg completed a symptom checklist. RESULTS:
      Analysis of variance indicates that those with a higher birthweight experience
      less minor illness. Regression analysis indicates that birthweight is
      significantly predictive of levels of some minor illnesses. CONCLUSION: This
      investigation adds a new dimension to Barker's hypothesis and shows that early
      environment can also affect levels of minor illness. It is suggested that
      susceptibility to minor illness may be explained by coactions between structure,
      function and environment prior to birth.

PMID- 11335869
TI  - Short Communication: Prolactogenic effects of etizolam.

PMID- 11335870
TI  - The Ethological Approach to the Study of Human Behavior.
AB  - Human ethology, which was established on the basis of classical zooethology, can
      be an inspirational contribution to the study of human behavior. The study of
      behavior in natural conditions is stimulating as well as the primary interest of
      ethologists in such behavioral patterns showing evolutionary success and benefits
      and which are called inborn or innate. The extensive area of human behavior,
      nonverbal communication, can be investigated also with the application of some
      ethological knowledge. Human ethology can bring significant insight to the
      evaluation of the pathology of human behavior in various medical disciplines. An
      important task of medical prediction (prognosis) can be made more reliable by
      considering the ethology. A specific attribute of the species Homo sapiens, his
      culture, is acknowledged and discussed through human ethology.

PMID- 11335873
TI  - The use in obstetrics of quantum theory as well as modern technology to decrease
      the morbidity and mortality of newborns and mothers during iatrogenic induced
      delivery.

PMID- 11335874
TI  - Effects of pineal peptide preparation Epithalamin on free-radical processes in
      humans and animals.
AB  - OBJECTIVES: The review on our own data on the effect of the pineal peptide
      preparation Epithalamin on free radical processes in rodents and humans is
      presented in this paper. RESULTS: The activity of Cu, Zn-superoxide dismutase
      (SOD) was found decreased in the brain of aged rats (30 months old) by 46.8% as
      compared to young animals. Concentration of Schiff's bases in the brain also went
      down with age (by 13.6%), while the level of dien conjugates (DC) and protein
      peroxidation (PPO) remained unchanged. General antioxidation activity (AOA) in
      the brain also remained stable with age. The liver of aged rats showed
      significant increase of Schiff's bases (by 27.1%) and PPO products (by 109.2%)
      and considerable decrease of SOD activity. The level of DC and general AOA in the
      liver remained unchanged with age. Considerable elevation of protein and lipid
      peroxidation products contents was registered in the blood serum of aged rats. At
      the same time, general AOA and SOD activity remarkably decreased. The results
      obtained evidence from both significant age-related alterations in the activity
      of free radical processes in animal organism and organic peculiarities of their
      dynamics. Application of peptide drug epithalamin suppressed significantly the
      intensity of peroxide chemoluminescence in the blood serum (2.8-fold) and lipid
      peroxide oxidation (LPO) expressed in the considerably decreased DC contents (4,1
      fold). The contents of Schiff's bases showed only a tendency towards decrease (by
      14.4%, p > 0.05) and PPO level remained unchanged. Epithalamin administration was
      followed by considerable (by 36.6%, p < 0.01) increase of general AOA and
      increased SOD activity (by 19.7%) in males. Epithalamin decreased significantly
      the contents of conjugated hydroperoxides and ketodienes in tissues of
      D.melanogaster females, increased catalase activity in drosophila males and
      females, and increased SOD activity in males of D.melanogaster by 41%. Humans
      reveal significant age-related decrease of antioxidation defence indices.
      CONCLUSION: Epithalamin administration to patients with age-related pathology
      eliminates imbalance in prooxidation and antioxidation systems.

PMID- 11335875
TI  - The changes in the ultrastructure of the cerebrovascular junction after traumatic
      injury of the cerebral cortex in rats.
AB  - OBJECTIVES: The effect of the traumatic injury of the cerebral cortex on the
      ultrastructure of the cerebrovascular junction was studied in rats. The aim of
      the present study is to describe the ultrastructural alterations in the
      cerebrovascular junction in rat cerebral cortex after traumatic injury. We were
      particularly interested in the alterations in endothelium, pericytes and the
      differentiated population of cerebral macrophages. MATERIAL AND METHODS: The
      observations were conducted four days (group I-five animals) and seven days
      (group II-five animals) after induction of cortical trauma. Traumatic injury was
      induced in the fronto-temporal region of cerebral cortex in general anesthesia
      with 20 mg/kg ketamine hydrochloride. RESULTS: In the first group we found the
      features of damage of the blood-brain barrier and migration of the morphological
      blood components to the perivascular space. The trauma caused necrosis and
      apoptosis within brain tissue. An important observation was the presence of
      numerous brain macrophages that participated in phagocytosis of damaged cellular
      elements. Additionally, we found an increase in the connective tissue ground
      substance around brain capillaries. In the second experimental group we noted an
      increased number of pericytes (1-3) near capillary walls. In some instances, the
      basement membrane surrounding the pericytes was interrupted and these cells were
      also located beyond the rim of the vessel wall. Some pericytes showed numerous
      phagolysosomes indicating that these cells belonged to perivascular macrophages.
      Moreover, we observed a population of phagocytes residing in close contact with
      neurons. These cells were different from the typical perivascular macrophages.
      CONCLUSIONS: These observations indicate that the traumatic injury of the brain
      results in mobilization of a heterogeneous population of brain macrophages. This
      study indicates that different subpopulations of macrophages emerge in the region
      of traumatic brain damage, and that the morphology and dynamics of these
      phagocytes changes and depends on the time elapsed after the initial traumatic
      incident.

PMID- 11335876
TI  - Efficacy of monochemotherapy with docetaxel (taxotere) in relation to prolactin
      secretion in heavily pretreated metastatic breast cancer.
AB  - OBJECTIVES: Recent data have suggested that the efficacy of cancer chemotherapy
      does not depend only on tumor-related characteristics, but also on patient
      biological status, namely immune and endocrine functions. In particular, it has
      been shown that prolactin (PRL) is a growth factor for breast cancer, and
      abnormally high blood levels of PRL have been described in metastatic breast
      cancer patients. The present study was performed to evaluate the efficacy of
      chemotherapy with taxanes in relation to PRL blood levels in metastatic breast
      cancer. MATERIAL & METHODS: The study included 20 metastatic breast cancer
      patients, who were treated with taxotere (100 mg/mq I.V. every 21 days) for at
      least 3 consecutive cycles. Serum levels of PRL were measured by RIA before the
      onset of treatment and at 21-days intervals. RESULTS: The clinical response
      consisted of partial response (PR) in 6, stable disease (SD) in 7 and progressive
      disease (PD) in the remaining 7 patients. Abnormally high pre-treatment levels of
      PRL were seen in 7/20 patients. The percent of patients who had PD in response to
      chemotherapy was significantly high in patients with pre-treatment
      hyperprolactinemia than in those with normal blood levels of PRL before therapy.
      CONCLUSIONS: This study shows that the evidence of abnormally high serum levels
      of PRL correlates with resistance to chemotherapy with taxanes in metastatic
      breast cancer. Therefore, a concomitant administration of anti-prolactinemic
      agents, such as bromocriptine, could enhance the efficacy of chemotherapy itself.

PMID- 11335877
TI  - Gestational progesterone suppresses embryotoxic action of the complement system
      to chick embryo.
AB  - OBJECTIVE: In this paper the relation between progesterone levels and embryotoxic
      effect of serum complement was studied. DESIGN: The aim of this study was to
      validate hypothesis that progesterone is strong inhibitor of complement
      embryotoxic action. SETTING: We used chick embryo like an experimental model for
      evidence of our hypothesis. We treated chick embryos by sera acquired from
      healthy pregnant woman with physiologically elevated levels of progesterone and
      normal complement activity. We investigated embryotoxicity of these sera. RESULT:
      We noticed a significant decrease of sera embryotoxicity inversely related to
      serum levels of progesterone. The main finding: The embryotoxicity of sera is
      reversally dependent on progesterone level. CONCLUSIONS: These findings bring a
      new knowledge to the role of progesterone and complement system mainly in initial
      stages of pregnancy and in some cases of spontaneous abortions.

PMID- 11335878
TI  - Incidence of autoimmune thyroiditis in interferon-alpha treated and untreated
      patients with chronic hepatitis C virus infection.
AB  - OBJECTIVES: To clarify the relationship between interferon-alpha (IFN-alpha)
      therapy and autoimmune thyroiditis in chronic hepatitis C virus (HCV) infection,
      we investigated a selected number of patients without basal thyroid dysfunctions.
      MATERIALS AND METHODS: 130 patients (average age: 20-70), with chronic HCV
      infection and without basal clinical and laboratory signs of autoimmune
      thyroiditis were divided into two groups: IFN-alpha treated (A) and untreated (B)
      patients. Group A received IFN-alpha (three million U.I./3 times a week) for six
      months; group B was followed for the same period. Thyroid peroxidase and
      thyroglobulin autoantibodies were measured by radioimmunoassay; thyroid function
      was measured by radioimmunoassay (free thyroxine and triiodothyronine) and
      immunoradiometric assay (thyroid stimulating hormone). RESULTS: After a 6-month
      period, thyroid autoantibodies positivity was documented in 21.1% of group A and
      in 10.3% of group B patients, both statistically relevant (p<0.001 and p<0.011,
      respectively). The comparison between the two groups was not statistically
      relevant (p=0.142). CONCLUSIONS: Our study showed a prevalence of de novo thyroid
      autoimmunity in chronic HCV patients treated with IFN-alpha, confirming previous
      data in literature. The lack of a significant difference between treated and
      untreated patients strongly suggests that the anti-thyroid autoimmune response is
      linked to the HCV infection itself. Moreover, IFN-alpha therapy probably does not
      represent a risk factor in renewing the autoimmune processes of the thyroid
      gland. Thyroid function and autoantibodies must be systematically monitored in
      patients with HCV infection, especially in female and IFN-alpha treated
      population, not only to verify the possible thyroid abnormalities but also to
      rule out concomitant autoimmune diseases.

PMID- 11335879
TI  - Anti-angiogenic activity of melatonin in advanced cancer patients.
AB  - OBJECTIVES: The anticancer activity of the indole melatonin has been explained to
      be due to its immunomodulatory, anti-prolferative and anti-oxidant effects,
      whereas at present no data are available about its possible influence on the
      angiogenesis, which has been shown to be one of the main biological mechanisms
      responsible for tumor dissemination. Vascular endothelial growth factor (VEGF) is
      the most active angiogenic factor, and the evidence of abnormally high blood
      levels or VEGF has been proven to be associated with poor prognosis in cancer
      patients. To investigate the influence of melatonin on angiogenesis, in this
      preliminary study we have evaluated the effects of melatonin therapy on VEGF
      blood levels in advanced cancer patients. MATERIAL & METHODS: The study included
      20 metastatic patients, who progressed on previous conventional antitumor
      therapies and for whom no other effective treatment was available. Melatonin was
      given orally at 20 mg/day in the evening for at least 2 months. Serum levels of
      VEGF were measured by an enzyme immunoassay on venous blood samples collected at
      15-day intervals. RESULTS: The clinical response consisted of minor response (MR)
      in 2, stable disease (SD) in 6 and progressive disease (PD) in the remaining 12
      patients. VEGF mean levels decreased on therapy, without, however, statistical
      differences with respect to the pre-treatment values. In contrast, by evaluating
      changes in VEGF levels in relation to the clinical response, non-progressing
      patients (MR + SD) showed a significant decline in VEGF mean concentrations,
      whereas no effect was achieved in progressing patients. CONCLUSIONS: This study,
      by showing that melatonin-induced control or the neoplastic growth is associated
      with a decline in VEGF secretion, would suggest that the pineal hormone may
      control tumor growth at least in part by acting as a natural anti-angiogenic
      molecule, with a following opposition or angiogenesis-dependent cancer
      proliferation.

PMID- 11335880
TI  - Hashimoto's disease during interferon-alpha therapy in a patient with pre
      treatment negative anti-thyroid autoantibodies and with the specific genetic
      susceptibility to the thyroid disease.
AB  - OBJECTIVES: The authors described a case of Hashimoto's disease during interferon
      alpha (IFN-alpha) treatment for chronic viral C hepatitis in a patient with the
      specific genetic susceptibility associated with the thyroid disease. RESULTS: A
      60-year-old woman with chronic active viral C hepatitis (HCV genotype = 3a)
      started IFN-alpha therapy in November '96. Before treatment thyroid function
      tests were normal and anti-thyroid (anti-thyroglobulin and anti-thyroid
      peroxidase) Abs were negative. During IFN therapy, serum aminotransferases fell
      within the normal range and viremia (serum HCV-RNA) became negative after one
      year. After 20 months, the patient presented clinical features of primary
      hypothyroidism. Anti-thyroid Abs were found positive. Hormonal, ultrasonographic,
      radioiodine scanning and fine needle aspiration findings were consistent with the
      diagnosis of Hashimoto's thyroiditis. The tissutal typing of the patient showed
      the presence of Human Leukocyte Antigen (HLA) DRB1*11 gene (corresponding to DR5
      antigen). IFN-alpha therapy was suspended and a treatment with l-T4 started.
      Chronic viral infection relapsed after the suspension of the IFN-alpha therapy.
      CONCLUSIONS: This case report showed that the clinical appearance of Hashimoto's
      disease after IFN-alpha therapy for chronic C hepatitis in our patient was
      associated with a specific genetic predisposition (DR5) for this pathology.
      Further studies are necessary to evaluate whether the study of HLA antigens may
      be a very useful tool to detect the patients with a predisposition to develop
      autoimmune thyroiditis, in order to make a early diagnosis of thyroid disorders
      during the IFN-alpha treatment.

PMID- 11335883
TI  - Focal ischemia in the cerebral cortex has an effect on the neurohypophysis. I.
      Ultrastructural changes in capillary vessels of the neurohypophysis after focal
      ischemia of the cerebral cortex.
AB  - OBJECTIVES: In our investigations we have reported that photochemical reaction
      leading to brain ischemia can also be precipitated with visible light from a non
      coherent light source. It was revealed that focal cerebral ischemia after
      photochemical reaction cause the alterations in the capillaries ultrastructure
      and perivascular spaces of the barrier-competent regions of the brain. The
      purpose of this study is to first characterize the ultrastructural morphological
      consequences of photochemically induced ischemia in the cerebral cortex on the
      capillaries of neurohypophysis as the barrier-free region of the brain. METHOD:
      We used a model of ischemic brain damage due to obliteration of microvessels
      following the photochemical reaction. Rats were treated with an intravenous
      injection of rose bengal and irradiated from a halogen lamp source through an
      intact cranium to precipitate microvascular damage. Material for electron
      microscopic studies were sampled from the neurohypophysis 1 and 4 days after
      irradiation (4 animals in each group) in experimental group and 1 and 4 days
      after a rose bengal injection in control group. RESULTS: Investigations in
      transmission electron microscopy revealed platelet aggregation on the endothelium
      preceded by its early ultrastructural damage. In the capillaries of the
      neurohypophysis, one and four days after irradiation, numerous microthrombi
      adhering to the damaged endothelium were present. The capillary vessels contained
      a continuous, rather than a fenestrated endothelium. The basement membrane was
      thickened, blurred and locally multiplicated. CONCLUSION: Our results show that
      experimentally-induced thrombosis of cortical microvessels leads to alterations
      in the capillaries of neurohypophysis.

PMID- 11335884
TI  - Focal ischemia in the cerebral cortex has an effect on the neurohypophysis. II.
      Angiogenesis in the neurohypophysis is a consequence of the focal ischemia in the
      cerebral cortex.
AB  - OBJECTIVES: Focal ischemia in the cerebral cortex has an effect on
      neurohypophysis. The morphological changes of microvessels of neurohypophysis
      were evaluated in a model of the cerebral infarction initiated by a photochemical
      reaction in the cerebral cortex. After photochemically induced platelet
      aggregation, we observed the morphological features of angiogenesis. METHOD: The
      model of photochemically-induced cerebral ischemia was used. Seven days after
      intravenous injection of rose bengal and irradiation from a halogen lamp source
      through an intact cranium, the sampled material from neurohypophysis is processed
      for transmission electron microscopy using standard procedures. RESULTS: We
      observed morphological features of the new vessel formation: the alterations in
      the endothelium and extracellular matrix during separation of the endothelial
      cell from each other in a "mother" vessel, the migration of the endothelial cells
      in the extracellular matrix, the communication of the lumen of the new and the
      "mother" vessels. CONCLUSION: We observed development of the angiogenic phenotype
      in the neurohypophysis after focal ischemia in the cerebral cortex. The
      endothelium, basement membrane and extracellular matrix undergo morphological
      alterations which lead to new blood vessel formation.

PMID- 11335885
TI  - Quantitative study on the effects of chronic ethanol administration on the testis
      of adult male rat.
AB  - OBJECTIVES: Considering the possibility that alcoholism induces gonadal
      dysfunction, the present work was designed to investigate the morphophysiology of
      rat testes submitted to experimental alcoholism. METHODS: Male Sprague-Dawley
      rats weighing 150+/-5 gm were chronically given 40% ethanol solution at a dose of
      3 g/kg body weight for 30 days. (3)H-thymidine autoradiographic investigations
      and histological studies were carried out to determine the proliferative activity
      and/or different stages of spermatogenesis in the seminiferous tubule cycle and
      Leydig cells. RESULTS: The 3H-thymidine autoradigraphic investigation revealed
      that there was a significant inhibition in the proliferative activity of the
      spermatogonia in all stages of the seminiferous tubule cycle in the alcohol
      treated rats versus controls as indicated by the values of (3)H-labelling
      indices. The histological and numerical investigations indicated that the alcohol
      treated rats presented testicular lesions including a significant decrease in the
      diameter of the seminiferous tubules, the number of different germ cells in all
      stages of the seminiferous tubule cycle and the presence of degenerative germ
      cells. In addition, there was a significant decrease in the number of Leydig
      cells. CONCLUSION: The present work suggests the deleterious effects of alcohol
      on the testes. These effects may be due to the effect of alcohol on the
      gonadotrophic cells of the pituitary gland and/or directly on the seminiferous
      tubules and Leydig cells.

PMID- 11335886
TI  - Protective role of melatonin against MPTP-induced mouse brain cell DNA
      fragmentation and apoptosis in vivo.
AB  - OBJECTIVES: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin
      that induces a Parkinsonian-type syndrome in animals which is similar to
      Parkinson's disease in humans. MPTP toxicity partially depends on the production
      of free radicals which in turn play a key role in the apoptotic death of neurons.
      In the present study melatonin, a potent free radical scavenger with
      antiapoptotic properties, was given to determine whether it would reduce
      oxidative stress in mice treated with MPTP. MATERIALS AND METHODS: Male mice were
      given MPTP with or without melatonin and the brain was studied either 6h, 24h, 7
      days or 15 days after the last MPTP injection. RESULTS: The results show that
      melatonin counteracted in vivo MPTP-induced apoptosis in midbrain neurons at 6
      and 24 h after MPTP treatment, and partially prevented apoptosis at 7 and 15 days
      after MPTP administration. MPTP treatment also produced time-dependent cell
      damage, whereas melatonin reduced the percentage of damaged cells at all time
      points, the effect being most evident at 15 days after treatment. Moreover,
      melatonin counteracted MPTP-dependent DNA fragmentation in the midbrain and
      striatum at 7 and 15 days after drug administration. CONCLUSION: These results
      support a role for melatonin in protecting neurons against MPTP toxicity in vivo,
      and suggest that its antiapoptotic action is one of the mechanisms by which
      melatonin protects neuronal cells from neurotoxic insults.

PMID- 11335887
TI  - Melatonin production in patients with duodenal ulcer.
AB  - OBJECTIVES. This work was designed to study melatonin (M) production levels in
      duodenal ulcer (DU) patients in the exacerbation and remission stages and in DU
      patients with a different course of DU in the exacerbation and remission stages.
      METHODS: DU patients (15 men aged 20 to 45, mean age 34,2 +/- 1,1 years) were
      studied. The control group included 11 healthy volunteers (men aged 20-45, mean
      age 32,5 +/- 1,4 years). M was measured by RIA-method using H(3)-labeled M in
      daily urine collected at 3-hour intervals (8 portions per day). Mathematical
      processing was carried out using ANOVA, Student's t-test, and cosinor analysis.
      Differences at p< or = 0,05 were considered to be significant. RESULTS: A strong
      disturbance of M secretion in DU patients both in the exacerbation and remission
      stages and a direct correlation between the degree of M production disturbance
      and severity of clinical course of DU were revealed. CONCLUSION: The obtained
      results suggest that circadian rhythms of M production are altered in DU
      patients. M was supposed to be involved in the pathogenesis of DU.

PMID- 11335888
TI  - Assessment of the relationship between circadian variations of salivary melatonin
      levels and type I collagen metabolism in postmenopausal obese women.
AB  - BACKGROUND: Few experimental and clinical studies show that melatonin (MEL) can
      play a significant part to modulate circadian bone metabolism. On this basis it
      was suggested that MEL secretion which altered during 24-h in obese women could
      be of importance to regulate bony mass defect after menopause. OBJECTIVE: The aim
      of the study was to prove if there were any connection between changes in 24-h
      profile of serum MEL levels and circadian metabolism of type I collagen in
      postmenopausal women with visceral obesity. METHODS: The relationship of 24-h
      profile of salivary MEL and circadian metabolism of type I collagen (as assessed
      by measuring saliva concentrations of carboxyterminal propeptide of type I
      procollagen--PICP and cross-linked carboxyterminal telopeptide of type I collagen
      -ICTP) was investigated in 26 women with visceral obesity (33.5 < BMI < 42.1
      kg/m(2)) and 18 healthy volunteers with correct body mass (21 < BMI < 24.5
      kg/m(2); 0.73 < WHR < 0.76). The specimens were collected at subjects' home at 3
      h intervals during a 24 h span. The age range of all subjects was 52-60 years.
      RESULTS: In all the obese women studied a tendency to suppress circadian levels
      of tested biochemical markers of bone metabolism was observed (especially
      regarding ICTP); those alterations were accompanied by substantial increment in
      MEL concentrations during the day. Significant and negative correlation was found
      between values of acrophase MEL and PICP rhythms and both amplitude and acrophase
      of MEL and ICTP rhythms. CONCLUSION: Our results confirm hypothesis that
      alterations in MEL concentrations might have a protective effect against
      postmenopausal loss of bone mass.

PMID- 11335889
TI  - Assessment of the relationship between dynamic pattern of nighttime levels of
      melatonin and chosen biochemical markers of bone metabolism in a rat model of
      postmenopausal osteoporosis.
AB  - BACKGROUND: Lately, there have been suggestions that bone mass changes occurring
      in postmenopausal women may remain related to melatonin. OBJECTIVE: To assess the
      relationship between the dynamic pattern of nighttime levels of melatonin and
      chosen biochemical markers of bone metabolism in ovariectomized rats--a model of
      postmenopausal osteoporosis. METHODS: Mature Wistar female rats were either
      ovariectomozed or underwent a sham operation. Following this they were killed at
      02:00AM at weekly intervals for 8 weeks after surgery. Serum levels of MEL at
      death related to the chosen biochemical markers of bone formation (alkaline
      phosphatase--ALP; carboxyterminal propeptide of type I procollagen--PICP, both in
      serum) and resorption (cross-linked carboxyterminal telopeptide of type I
      collagen--ICTP in serum; hydroxyproline--HYP and total calcium--Ca, both excreted
      in urine). RESULTS: In all ovariectomized rats changes of examined indices of
      bone tissue metabolism were found to be dynamic and statistically significant
      relative to the control group; however the changes were more pronounced regarding
      resorption markers. Following ovariectomy, the increase in ALP and PICP values
      was found to begin at the 4th and the 1st week, while that in ICTP, HYP and Ca at
      the 2nd, the 1st and the 1st week, respectively. The ALP and PICP values remained
      at a similar level until the end of observation, whereas ICTP, HYP and Ca
      gradually decreased. MEL levels were decreased during the 2nd week following
      surgery and slightly increased 2 weeks later. The serum MEL levels in the
      ovariectomized group were significantly and negatively correlated with serum ICTP
      and both urinary HYP and Ca levels. CONCLUSION: Our findings in rats seem to
      corroborate the concept of secondary changes in MEL levels co-participating in
      the development of bone mass changes characteristic for postmenopausal
      osteoporosis.

PMID- 11335890
TI  - A study of light/dark rhythm of melatonin in relation to cortisol and prolactin
      secretion in schizophrenia.
AB  - OBJECTIVES: Recent studies have suggested the involvement of the pineal gland and
      its main hormone melatonin (MLT) in the pathogenesis of psychiatric disturbances,
      namely the depressive syndrome. In contrast, the behavior of MLT secretion in
      schizophrenia is still controversial. MATERIAL & METHODS: The present study was
      carried out to analyze light/dark rhythm of MLT secretion in relation to that of
      cortisol and prolactin (PRL) in schizophrenic patients. The study included 13
      schizophrenic patients, 8 of whom were untreated, while the other 5 patients were
      on neuroleptic therapy. Serum levels of MLT, PRL and cortisol were measured by
      RIA on venous blood samples collected at 8 A.M., 12 A.M., 8 P.M. and 1 A.M. The
      control group consisted of 20 age-matched healthy subjects. RESULTS: A
      physiological nocturnal increase in MLT levels occurred in 6/13 patients, whereas
      the other 7 patients showed an abnormally low MLT peak during the night.
      Moreover, both light and night mean levels of MLT were significantly lower in
      patients than in controls. In addition, mean nocturnal levels of MLT were
      significantly lower in chronic patients than in those evaluated at the onset of
      disease. Cortisol rhythm was normal in 11/13 patients, whereas PRL levels were
      abnormally high in 10/13 patients. CONCLUSIONS: This preliminary study would
      suggest that schizophrenia may be associated with a diminished secretion of MLT
      from the pineal gland, and pineal deficiency would be more evident in the chronic
      disease. Finally, pineal alterations have appeared to be associated with an
      altered secretion of PRL and cortisol, by suggesting that the schizophrenic
      disease may be characterized by marked neuroendocrine disturbances, whose physio
      pathological and prognostic significance needs to be established by successive
      clinical investigations.

PMID- 11335891
TI  - Effects of 5' regulatory-region polymorphisms on paraoxonase-gene (PON1)
      expression.
AB  - Human HDL-associated paraoxonase (PON1) hydrolyzes a number of toxic
      organophosphorous compounds and reduces oxidation of LDLs and HDLs. These
      properties of PON1 account for its ability to protect against pesticide
      poisonings and atherosclerosis. PON1 also hydrolyzes a number of lactone and
      cyclic-carbonate drugs. Among individuals in a population, PON1 levels vary
      widely. We previously identified three polymorphisms in the PON1 regulatory
      region that affect expression levels in cultured human hepatocytes. In this
      study, we determined the genotypes of three regulatory-region polymorphisms for
      376 white individuals and examined their effect on plasma-PON1 levels, determined
      by rates of phenylacetate hydrolysis. The -108 polymorphism had a significant
      effect on PON1-activity level, whereas the -162 polymorphism had a lesser effect.
      The -909 polymorphism, which is in linkage disequilibrium with the other sites,
      appears to have little or no independent effect on PON1-activity level in vivo.
      Other studies have found that the L55M polymorphism in the PON1-coding region is
      associated with differences in both PON1-mRNA and PON1-activity levels. The
      results presented here indicate that the L55M effect of lowered activity is not
      due to the amino acid change but is, rather, largely due to linkage
      disequilibrium with the -108 regulatory-region polymorphism. The codon 55
      polymorphism marginally appeared to account for 15.3% of the variance in PON1
      activity, but this dropped to 5% after adjustments for the effects of the -108
      and Q192R polymorphisms were made. The -108C/T polymorphism accounted for 22.8%
      of the observed variability in PON1-expression levels, which was much greater
      than that attributable to the other PON1 polymorphisms. We also identified four
      sequence differences in the 3' UTR of the PON1 mRNA.

PMID- 11335892
TI  - Concordance between the CC chemokine receptor 5 genetic determinants that alter
      risks of transmission and disease progression in children exposed perinatally to
      human immunodeficiency virus.
AB  - If CC chemokine receptor 5 (CCR5)-dependent mechanisms at the time of initial
      virus exposure are important determinants of virus entry and disease outcome,
      then the polymorphisms in CCR5 that influence risk of transmission and disease
      progression should be similar; this hypothesis was tested in a cohort of 649
      Argentinean children exposed perinatally to human immunodeficiency virus type 1
      (HIV-1). Two lines of evidence support this hypothesis. First, CCR5 haplotype
      pairs associated with enhanced risk of transmission were the chief predictors of
      a faster disease course. Second, some of the haplotype pairs associated with
      altered rates of transmission and disease progression in children were similar to
      those that we previously found influenced outcome in European American adults.
      This concordance suggests that CCR5 haplotypes may serve as genetic rheostats
      that influence events occurring shortly after initial virus exposure, dictating
      not only virus entry but, by extension, also the extent of early viral
      replication.

PMID- 11335893
TI  - The life-sparing potential of mammographic screening.

PMID- 11335894
TI  - Translocation t(17;18)(q10;q10): a new nonrandom chromosomal translocation of
      clonal evolution in chronic myeloid leukemia.

PMID- 11335895
TI  - Estimating the effect of an intensive surveillance program on stage of breast
      carcinoma at diagnosis: a propensity score analysis.
AB  - BACKGROUND: The authors used propensity score adjustment to investigate the
      impact of intensive screening on stage of breast carcinoma at diagnosis in women
      who were at elevated risk for breast carcinoma. METHODS: The authors compared 58
      women participating in a surveillance program at the Columbia Presbyterian
      Medical Center of New York Presbyterian Hospital who developed breast carcinoma
      with 3022 nonparticipating breast carcinoma patients. A propensity score was
      constructed for each woman by using important background covariates, and
      multivariable regression modeling was used to estimate the association of program
      membership with disease stage after adjusting for the propensity score. RESULTS:
      Before propensity score adjustment, nine baseline covariates significantly
      differed between the two groups (number of pregnancies, number of births, age at
      first delivery, race, how the tumor was discovered, history of prior breast
      disease, breast carcinoma in mother, breast carcinoma in maternal aunt, and
      breast carcinoma in sister), and there was a significant difference in stage at
      diagnosis. After adjustment, no significant differences remained. Program
      participants were more likely to have lower stage tumors at diagnosis than
      nonparticipants, but this association did not reach statistical significance
      (odds ratio, 1.52; 95% confidence interval, 0.94--2.46). CONCLUSIONS: Propensity
      score methods can remove bias in treatment comparisons in observational studies.
      An intensive surveillance program at a major cancer center may have had some
      effect on improving stage at diagnosis, but this effect was not statistically
      significant.

PMID- 11335896
TI  - Mammography utilization after a benign breast biopsy among Hispanic and non
      Hispanic women.
AB  - BACKGROUND: In spite of the effectiveness of mammography screening for early
      detection of breast carcinoma, the use of screening mammography varies widely
      across racial and ethnic groups. Recently, concerns have been raised about the
      potential adverse effect a benign breast biopsy may have on subsequent
      mammography utilization, including subsequent use among minority women. METHODS:
      Computerized health care claims data for 1991 through 1997 from a managed care
      organization were used to compare mammography use among Hispanic and non-Hispanic
      women who had had a mammogram followed by an incisional or excisional benign
      breast biopsy to women who had had a mammogram and no biopsy. Through survival
      analysis methods, the time-to-next mammogram was compared among these three
      groups. RESULTS: The sample included 693 (3.2%) and 289 (1.3%) women who had had
      a mammogram followed by an incisional biopsy or an excisional biopsy,
      respectively, and 20,540 (95.4%) women who had had a mammogram and no biopsy.
      Both Hispanic and non-Hispanic women with a biopsy returned sooner for subsequent
      mammograms than women without a biopsy (P < 0.0001). Hispanic women without a
      biopsy returned later than non-Hispanic women without a biopsy (P < 0.0001).
      However, Hispanic women with an excisional biopsy returned sooner than non
      Hispanic women (P < 0.05). CONCLUSIONS: Within a managed care organization, both
      Hispanic and non-Hispanic women who had had a mammogram followed by a benign
      breast biopsy returned sooner for a subsequent mammogram than women who had had a
      mammogram and no biopsy. However, ethnic differences in time-to-next mammogram
      were observed for women without a biopsy and those with an excisional biopsy.
      Hispanic women without a biopsy returned later for a subsequent mammogram than
      non-Hispanic women in similar groups, but those with an excisional biopsy
      returned sooner.

PMID- 11335897
TI  - Beyond randomized controlled trials: organized mammographic screening
      substantially reduces breast carcinoma mortality.
AB  - BACKGROUND: The efficacy of mammographic screening in the reduction of breast
      carcinoma mortality has been demonstrated in randomized controlled trials.
      However, the evaluation of organized screening outside of research settings (so
      called "service screening") faces unique methodologic and conceptual challenges.
      The current study describes the evaluation of organized mammography screening in
      a clinical setting and demonstrates the benefit obtained from service screening
      in two Swedish counties. METHODS: In the group of subjects ages 20--69 years,
      there were 6807 women diagnosed with breast carcinoma over a 29-year period in 2
      counties in Sweden and 1863 breast carcinoma deaths. All patients were classified
      from patient charts based on their screening status (i.e., whether they had been
      invited to undergo screening and whether they actually had undergone screening).
      The number of women who lived in the 2 counties during the 29-year study period
      was provided by the Central Bureau of Statistics. Breast carcinoma-specific
      mortality was compared across three time periods: 1) 1968--1977, when no
      screening was taking place because mammography had not been introduced; 2) 1978-
      1987, the approximate period of the Two-County randomized controlled trial of
      screening in women ages 40--74 years; and 3) 1988--1996, when all women in the 2
      counties ages 40--69 years were invited to undergo screening (service screening).
      When comparing breast carcinoma mortality in screened women with that in women
      diagnosed before screening was introduced, a correction for self-selection bias
      was incorporated to prevent overestimation of the benefit of screening. RESULTS:
      The mortality from incident breast carcinoma diagnosed in women ages 40-69 years
      who actually were screened during the service screening period (1988--1996)
      declined significantly by 63% (relative risk [RR] = 0.37; 95% CI, 0.30--0.46)
      compared with breast carcinoma mortality during the time period when no screening
      was available (1968--1977). The mortality decline was 50% (RR = 0.50; 95% CI,
      0.41--0.60) when breast carcinoma mortality among all women who were invited to
      undergo screening (nonattendees included) was compared with breast cancer
      mortality during the time period when no screening was available (1968--1977).
      The reduction in mortality observed during the service screening period, adjusted
      for selection bias, was 48% (RR = 0.52; 95% CI, 0.43--0.63). No significant
      change in breast carcinoma mortality was observed over the three time periods in
      women who did not undergo screening. This group included women ages 20--39 years
      because these individuals were never invited to undergo screening, and women ages
      40--69 years who did not undergo screening (not invited during the randomized
      trial or invited during the second and third time periods but declined).
      CONCLUSIONS: Regular mammographic screening resulted in a 63% reduction in breast
      carcinoma death among women who actually underwent screening. The policy of
      invitation to organized screening with mammography appears to have reduced breast
      carcinoma mortality by 50% in these 2 counties.

PMID- 11335898
TI  - Gastric carcinoma after surgical treatment of peptic ulcer: an analysis of
      morphologic features and a comparison with cancer in the nonoperated stomach.
AB  - BACKGROUND: Surgery for peptic ulcer is associated with an increased risk of
      later development of gastric carcinoma. This risk applies to cancer occurring in
      the distal stomach, not at the cardia. Mucosal alterations occurring in the
      nonneoplastic mucosa, adjacent to postgastrectomy carcinomas, are currently
      poorly defined. METHODS: Between 1975 and 1995, the authors collected records of
      76 patients with gastric carcinoma developing after previous ulcer surgery.
      Thirty-three gastrectomy specimens were available for study and were compared
      with a control series of gastric carcinomas occurring in the intact stomach.
      Morphologic features studied were macroscopic findings, tumor type, extent of
      inflammation, atrophy, intestinal metaplasia, reactive gastropathy, and presence
      of Helicobacter pylori. When possible, a semiquantitative grading system (Sydney
      system) was used. RESULTS: The 33 patients with resected carcinoma after ulcer
      surgery were representative of the total 76 patients. There were no differences
      between the seven postulcer surgery cardia carcinomas and the control cardia
      carcinomas. The 18 distal carcinomas occurring after prior gastrectomy had
      significantly less intestinal metaplasia and Helicobacter pylori in the
      nonneoplastic mucosa than did the controls. Eight distal carcinomas occurring
      after a vagotomy and pyloroplasty had adjacent mucosa with findings intermediate
      between the gastrectomy carcinomas and the controls. CONCLUSIONS: The differences
      shown suggest that for distally located postgastrectomy carcinomas Helicobacter
      pylori infection with extensive intestinal metaplasia may be relatively less
      important in pathogenesis and that intestinal reflux with reactive gastropathy
      more important. There was no evidence to support a different mechanism of
      pathogenesis for postsurgical carcinomas occurring at the cardia from that of
      control cardia carcinomas.

PMID- 11335899
TI  - Intratumoral concentrations of tissue inhibitor of matrix metalloproteinase 1 in
      patients with gastric carcinoma a new biomartker for invasion and its impact on
      survival.
AB  - BACKGROUND: Previously, the authors clarified that the plasma concentration of
      tissue inhibitor of matrix metalloproteinase 1 (TIMP-1) in patients with gastric
      carcinoma was a significant predictor of tumor invasiveness and metastasis.
      METHODS: To further clarify the clinical significance of TIMP-1, the authors used
      an enzyme-linked immunoassay to assess TIMP-1 protein concentrations in samples
      of tumor tissue from 86 patients who underwent primary resection for gastric
      carcinoma. Concentrations in samples of normal gastric mucosa from 73 of these
      patients also were assessed. RESULTS: Tissue TIMP-1 concentrations were
      significantly greater in gastric tumors than in normal gastric mucosa and were
      associated significantly with a variety of pathologic factors, including
      macroscopic type, depth of tumor invasion in the gastric wall, presence of
      lymphatic vessel invasion, pattern of tumor infiltration into the surrounding
      tissue, and disease stage. Significantly greater TIMP-1 concentrations were found
      in tumors that were exposed to the serosal surface compared with tumors that were
      limited to the submucosal layer. TIMP-1 protein was significantly greater in
      tumors with lymphatic vessel invasion, an infiltrative pattern into the
      surrounding tissue (INF-gamma), and in tumors from patients with Stage III
      disease. Survival was significantly poorer in patients with TIMP-1 concentrations
      > or = 10.0 ng/mg total protein. When patients were stratified by disease stage,
      survival was significantly different in patients with Stage III disease.
      Multivariate analysis demonstrated that intratumoral concentrations of TIMP-1
      were the most significant independent factor for survival. CONCLUSIONS: These
      findings suggest that the intratumoral concentration of TIMP-1 protein may be a
      good indicator of tumor aggressiveness and can serve as a significant independent
      predictor of survival in patients with gastric carcinoma.

PMID- 11335900
TI  - Inverse relation between levels of p27(Kip1) and of its ubiquitin ligase subunit
      Skp2 in colorectal carcinomas.
AB  - BACKGROUND: Previous studies have shown that low levels of p27(Kip1), an
      inhibitor of G1 cyclin-dependent kinases, are associated with high aggressiveness
      and poor prognosis in a variety of cancers. Decreased levels of p27 are caused,
      at least in part, by acceleration of the rate of its ubiquitin-mediated
      degradation. In cultured cells and cell-free biochemical systems, it has been
      shown that p27 is targeted for degradation by a ubiquitin ligase complex that
      contains Skp2 (S-phase kinase-associated protein 2) as the specific substrate
      recognizing and rate-limiting subunit. This investigation was undertaken to
      examine the possible relation between levels of p27 and of its specific ubiquitin
      ligase subunit Skp2 in human cancers. METHODS: Quick-frozen colorectal tumor
      samples from 20 patients were homogenized at 0 degrees C in buffer containing a
      mixture of protease inhibitors. Samples were separated by electrophoresis on
      sodium dodecyl sulfate-polyacrylamide gels, transferred to nitrocellulose, and
      probed with highly specific monoclonal antibodies directed against Skp2 and p27.
      The expression of Skp2 also was examined by immunohistochemistry using formalin
      fixed, paraffin embedded tissue sections from the same cases. RESULTS: A strongly
      significant inverse correlation was found between levels of Skp2 and p27 (r = 
      0.812; P < 0.0001). Thus, decreased levels of p27 were associated with strongly
      increased levels of Skp2, whereas high levels of p27 coincided with low levels of
      Skp2. Immunohistochemical examination of Skp2 expression agreed with immunoblot
      analysis in 89% of cases. CONCLUSIONS: The results are compatible with the notion
      that increased expression of Skp2 may have a causative role in decreasing the
      levels of p27 in aggressive colorectal carcinomas.

PMID- 11335901
TI  - Tumor growth pattern and thymidine phosphorylase expression are related with the
      risk of hematogenous metastasis in patients with Astler Coller B1/B2 colorectal
      carcinoma.
AB  - BACKGROUND: The benefit of adjuvant chemotherapy appears to be limited for
      patients with Astler Coller B1/B2 colorectal carcinoma but may be better in a
      subgroup of patients with a high recurrence risk. In the current case-control
      analysis, the authors evaluated whether patients with a high risk of hematogenous
      metastasis could be identified by means of a thorough histologic and
      immunohistochemical examination of the resection specimens. METHODS: A database
      was built for all patients treated in a general teaching hospital for colorectal
      carcinoma between 1985 and 1995. From this database, all patients with an Astler
      Coller B1 or B2 tumor who subsequently had developed hematogenous metastases were
      taken as cases. For each case, three matched controls (age, Astler Coller, year
      of diagnosis) without metachronous metastases were selected. The resection
      specimens of cases and controls were blindly examined by two observers for the
      following: World Health Organization (WHO) classification; differentiation grade;
      growth pattern; lymphocytic, fibroblastic, and eosinophilic reaction;
      angioinvasion; number of lymph nodes examined; expression of E-cadherin, vascular
      endothelial growth factor and thymidine phosphorylase (TP); P53; microvessel
      density. RESULTS: Twenty-two cases and 65 controls were included in the analysis.
      Tumor growth pattern and tumor TP expression both independently contributed to
      recurrence risk. With these 2 variables, 4 subgroups could be identified with a
      recurrence risk ranging from 0% to 42%. CONCLUSIONS: Tumor growth pattern and
      degree of TP expression both appear to be related to the recurrence risk.
      Prospective trials should point out whether these variables can be implemented in
      the decision making concerning adjuvant chemotherapy.

PMID- 11335902
TI  - Surrogate endpoint biomarkers and their modulation in cervical chemoprevention
      trials.
AB  - BACKGROUND: Surrogate endpoint biomarkers (SEBs) are used as intermediate
      indicators of a reduction in cancer incidence in chemoprevention studies. SEBs
      should be expressed differentially in normal and high risk tissue; appear at a
      well defined stage of carcinogenesis; be studied with reasonable sensitivity,
      specificity, and accuracy; and be modulated in chemoprevention trials. The
      concept of SEBs may be useful in the trials of many new therapies. METHODS: The
      current review includes a comprehensive review of the literature. Many SEBs have
      been the subject of intense study and include quantitative histopathology and
      cytology, proliferation markers, regulation markers, differentiation markers,
      general genomic instability markers, and tissue maintenance markers. Because of
      the critical biologic and epidemiologic role of the human papillomavirus (HPV) in
      cervical carcinogenesis, the relation between these markers and HPV should be
      considered. In addition, biomarkers of HPV infection and its regression should be
      sought. RESULTS: Several chemoprevention trials have been published that have
      included the use of SEBs. The biomarkers that appear most promising in these
      clinical trials can be measured quantitatively and reproducibly: quantitative
      histology and cytology, proliferating cell nuclear antigen (PCNA), MIB-1, MPM-2,
      HPV viral load, epidermal growth factor receptor, polyamines, and ploidy. The
      markers that have been demonstrated to be modulated in chemoprevention trials in
      the literature are quantitative histology and cytology, PCNA, MPM-2, HPV viral
      load, and polyamines. CONCLUSIONS: The surrogate endpoint biomarkers of most
      interest in future research should correlate well with HPV infection, be
      modulated by several therapeutic agents, and have limited variability and ease in
      measurement.

PMID- 11335903
TI  - Significance of perivascular lymphocytic infiltrates in endometrial carcinoma.
AB  - BACKGROUND: The objective of this study was to clarify the significance of
      perivascular lymphocytic infiltrates (PLI) in endometrial carcinoma. METHODS: The
      pathologic records of 127 patients with endometrioid type adenocarcinoma confined
      to the uterus were reviewed retrospectively. The patients were divided into 4
      groups based on the presence or absence of vascular invasion (VI) and PLI: VI-PLI
      (n = 87), VI-PLI+ (n = 7), VI+PLI+ (n = 22), and VI+PLI- (n = 11). Pathologic
      features including tumor grade, myometrial invasion, cervical involvement,
      vascular invasion-associated changes (VIAC; VI and/or PLI), tumor size, ovarian
      metastasis, and pelvic lymph node metastasis were assessed statistically.
      RESULTS: Selective pelvic lymphadenectomy was performed in 108 patients, and
      metastasis was identified in 6 cases (5.6%). Lymph node metastasis was the only
      independent variable related to recurrence (Cox regression analysis, P = 0.0008).
      Perivascular lymphocytic infiltrates correlated closely with VI (Fisher exact
      test, P < 0.0001). Vascular invasion-associated changes was the best predictor of
      lymph node metastasis (logistic regression analysis, P = 0.039), but among the
      three categories of VIAC, only the VI+PLI- group was significantly associated
      with lymph node metastasis (P = 0.0045). The odds ratios of VI+PLI- and VI+PLI+
      cases for lymph node metastasis were 64.54 and 3.24, respectively. CONCLUSIONS:
      Although VIAC is the best predictor of lymph node metastasis, the presence of PLI
      is associated with a lower risk of lymph node metastasis among VIAC groups.

PMID- 11335904
TI  - Enteral nutrition during the treatment of head and neck carcinoma: is a
      percutaneous endoscopic gastrostomy tube preferable to a nasogastric tube?
AB  - BACKGROUND: Multimodality treatments for patients with squamous cell head and
      neck carcinoma often produce significant mucositis and dysphagia, mandating
      enteral nutritional support. Patient preference has resulted in the increasing
      use of percutaneous endoscopic gastrostomy (PEG) tubes rather than nasogastric
      (NG) tubes. Anecdotal observations of prolonged PEG dependence and of a need for
      pharyngoesophageal dilatation in PEG patients prompted a retrospective review of
      the use of both types of feeding tubes. METHODS: Patients who were treated on
      clinical trials of radiotherapy or chemoradiotherapy for squamous cell head and
      neck carcinoma between 1989 and 1997 were reviewed retrospectively. Data were
      gathered regarding demographics, primary tumor site, T and N classifications, and
      the need for feeding tube placement. In patients requiring feeding tubes, the
      type and duration of the feeding tube, the need for tracheostomy, the need for
      pharyngoesophageal dilatation, and the degree of mucositis and dysphagia at
      baseline and at 1 month, 3 months, 6 months, and 12 months after beginning
      treatment were recorded. Comparisons were then made between the NG and the PEG
      groups. RESULTS: Ninety-one feeding tubes were placed in 158 patients over the 8
      year interval. A hypopharyngeal primary site, female gender, a T4 primary tumor,
      and treatment with chemoradiotherapy were predictive of a need for feeding tube
      placement. NG tubes were placed in 29 patients, and PEG tubes were placed in 62
      patients. PEG patients had more dysphagia at 3 months (59% vs. 30%, respectively;
      P = 0.015) and at 6 months (30% vs. 8%, respectively; P = 0.029) than NG
      patients. The median tube duration was 28 weeks for PEG patients compared with 8
      weeks for NG patients, (P < 0.001). Twenty-three percent of PEG patients needed
      pharyngoesophageal dilatation compared with 4% of NG patients (P = 0.022). These
      end points could not be correlated with age, stage, primary tumor site, or
      tracheostomy placement. CONCLUSIONS: Although patients treated for head and neck
      carcinoma find that the PEG tube is a more acceptable route for enteral nutrition
      than the NG tube, in the authors' experience, a PEG tube was required for longer
      periods of time and was associated with more persistent dysphagia and an
      increased need for pharyngoesophageal dilatation. A randomized prospective trial
      is needed to test these observations.

PMID- 11335905
TI  - Interstitial photodynamic therapy with rotating and reciprocating optical fibers.
AB  - BACKGROUND: Photodynamic therapy (PDT) is an effective treatment modality that
      allows selective destruction of malignant tumor cells. However, because of the
      difficulty in exposing deeper areas of tumors, the modality has strictly limited
      indications. In this study, the authors introduce a new method for delivering
      laser light to a three-dimensional, wide area with the purpose of improving the
      therapeutic value of PDT. METHODS: Three patients with squamous cell carcinoma of
      the tongue were treated with the present course. After administering porfimer
      sodium, laser-proof tubes were inserted through the tumor, and optical fibers
      were passed through the tubes. Pulse laser was emitted from the obliquely
      prepared fiber tip and distributed toward the target area while rotating and
      reciprocating the optical fiber. RESULTS: Two patients achieved a complete
      response without any complications or functional disabilities. The third patient,
      however, had a partial response and required surgery. CONCLUSIONS: The results
      indicate the capability of distributing laser light to an entire area of solid
      tumor. However, the ideal dose of laser light for the treatment of tumors remains
      unknown. Interstitial PDT will be more efficacious and reliable after the
      dosimetry is established.

PMID- 11335906
TI  - Current approaches and perspectives in the therapy of medullary thyroid
      carcinoma.
AB  - BACKGROUND: Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor derived
      from parafollicular cells. At present, surgery is the most important treatment
      for MTC. METHODS: We describe the current approaches of MTC treatment (surgery,
      chemotherapy, radiation therapy, and biologic therapy). RESULTS: MTC is currently
      approached surgically in the main part through total thyroidectomy and
      compartment-oriented microdissection of cervicomediastinal lymph nodes.
      Substitutive l-thyroxine administration together with close clinical monitoring
      and the measurement of basal and stimulated serum calcitonin are subsequently
      performed. Radiotherapy and chemotherapy play a marginal role in advanced MTC.
      Recently, it has been found that somatostatin analogs and type I interferon are
      able to control the neuroendocrine symptoms induced by advanced MTC and that they
      provide clinical benefit by improving the lifestyle of these patients.
      CONCLUSION: Although these agents are poorly active in inducing a shrinkage in
      tumor mass, the combined use of different biologic agents and cytotoxic drugs
      needs to be explored in advanced MTC. However, at present, surgery is the only
      curative treatment for MTC.

PMID- 11335907
TI  - Long term response in a patient with neoplastic meningitis secondary to melanoma
      treated with (131)I-radiolabeled antichondroitin proteoglycan sulfate Mel-14
      F(ab')(2): a case study.
AB  - Even with novel chemotherapeutic agents and external beam radiation therapy, the
      prognosis of neoplastic meningitis secondary to malignant melanoma is still
      dismal. The authors report a case study of a 46-year-old white female who
      presented with progressive hearing loss, severe headaches, nausea, vomiting, and
      a rapid decline in neurologic status. She was referred to Duke University Medical
      Center after conventional chemotherapy for malignant melanoma failed. She was
      enrolled in a Phase I trial of (131)I-labeled monoclonal antibody Mel-14
      F(ab')(2) fragment administered intrathecally. Within a year after her treatment,
      she recovered, having a normal neurologic exam except for residual bilateral
      hearing loss. The authors discuss dosimetry, preclinical, and clinical studies
      conducted with Mel-14 F(ab')(2) and introduce a potentially promising therapy
      option in the treatment of neoplastic meningitis in patients with malignant
      melanoma. Currently, the patient remains neurologically normal except for a mild
      bilateral hearing loss more than 4 years after treatment and has no radiographic
      evidence of neoplastic meningitis.

PMID- 11335908
TI  - Burden of illness associated with metastatic melanoma: an audit of 100
      consecutive referral center cases.
AB  - BACKGROUND: Although long-term survival in patients with metastatic melanoma (MM)
      is infrequent, response to a variety of cytotoxic and immunotherapies occurs and
      survival varies based on the site of metastases. Because different patterns of
      care of MM are likely to vary substantially in their intensity and resource use,
      the authors audited care at a regional referral center. METHODS: The records of
      100 consecutive new patients with MM who presented at the University of
      Pittsburgh Cancer Institute (UPCI) after January 1997 were audited. Demographics,
      disease sites, and treatment prior to presentation at UPCI as well as the
      diagnostic and therapeutic methods undertaken at UPCI were tracked monthly with
      regard to inpatient and outpatient activity. RESULTS: The median age of the
      patient cohort was 51 years was a median 2.2 years after the time of initial
      diagnosis. Eighty-two percent of the patients had died and only 8% had been lost
      to long-term follow-up. Eighty-seven percent of patients had been referred to
      UPCI and 28% had received some treatment prior to presenting at UPCI. The median
      survival was 9.0 months. The lung was the most common symptomatic site and 38% of
      patients developed central nervous system (CNS) metastases. Eighty-four percent
      of patients initially were treated on a research protocol 30% of whom were part
      of a Phase III study. Twenty-nine percent of the patients were never
      hospitalized. The most common reason for hospitalization was elective treatment
      with high-dose interleukin-2. Lifetime hospital days averaged only 7.3 days.
      Therapeutic actions (if ever given) by category type were surgery in 23% of
      patients, radiation therapy in 44%, immunotherapy in 75%, and chemotherapy in
      51%. Using assigned values for the identified resources used, the approximate
      cost per patient averaged $59,400. CONCLUSIONS: The current audit of MM patients
      demonstrated that lung and CNS metastases dominate a broad variety of
      complications, that clinical trial participation was the norm, that
      hospitalizations occurred relatively infrequently, and that the direct health
      care costs of current treatment patterns are among the highest for all
      malignancies. Medical auditing of contemporary American cancer care provides
      meaningful insights into its patterns of care.

PMID- 11335909
TI  - Clinical and histologic features of level 2 cutaneous malignant melanoma
      associated with metastasis.
AB  - BACKGROUND: Metastatic melanoma developing in patients with a level 2 primary
      cutaneous malignant melanoma (CMM) is rare but has been reported in studies with
      follow-up periods ranging up to 15 years. The objective of this study was to
      investigate level 2 CMM associated with metastasis in a population-based
      retrospective study. METHODS: In this retrospective population-based study, all
      level 2 CMMs associated with metastases were identified in Western Australia
      during 1982-1989 and were followed up to the end of 1996. RESULTS: Pathology
      reports of 2834 patients were examined. Of these, 1716 had a CMM of maximum tumor
      thickness 1 mm or less recorded on the pathology report. Of these, 67 had a
      metastatic melanoma reported on follow-up. Histologic review of these 67 cases
      under blind conditions identified 5 cases with a level 2 primary CMM followed by
      metastasis without another primary CMM. All these level 2 CMM showed established
      regression. Eight other patients were identified with a level 2 CMM, metastatic
      melanoma, and another primary CMM of at least level 3 invasion. These subsequent
      primaries occurred before the metastasis had been reported. CONCLUSIONS: These
      findings suggest that metastasis from level 2 CMM without regression is very
      rare, if it occurs at all.

PMID- 11335910
TI  - Phase I and pharmacokinetic study of a stable, polyethylene-glycolated liposomal
      doxorubicin in patients with solid tumors: the relation between pharmacokinetic
      property and toxicity.
AB  - BACKGROUND: Compared with free drug, sterically stabilized liposomal drug has
      prolonged circulation time and, thereby, higher tumor selectivity and antitumor
      activity. The stability in plasma is an important consideration in the
      formulation of clinically useful liposomal drug. A Phase I study of a stable
      liposomal doxorubicin with polyethylene glycol (PEG) coating and phospholipid
      component of distearoyl phosphatidylcholine (DSPC) was performed to characterize
      its pharmacokinetic properties, toxicity profile, and maximal tolerated dose.
      METHODS: The starting dose was 30 mg/m(2) every 3 weeks with an increment of 10
      mg/m(2) for each level. A cohort of at least three patients was entered for each
      level. Dose escalation stopped when more than one-third of patients had dose
      limiting toxicity (DLT), which was equal to or more than Grade 3 nonhematologic
      toxicity. Blood was sampled immediately before and at 5 minutes, 2 hours, 4
      hours, 10 hours, 24 hours, 48 hours, 72 hours, and 168 hours after the completion
      of PEGylated liposomal doxorubicin (PLD) infusion. Plasma level of doxorubicin
      was determined with fluorometry, and the pharmacokinetic properties were
      analyzed. RESULTS: Twenty-six patients were entered, and 101 courses were
      studied. This DSPC PLD had a steady-state distribution volume (Vss) of 2.4 +/-
      0.9 liters (mean +/- standard deviation), a clearance of 0.027 +/- 0.010 liters
      per hour, and a beta half-life of 65.0 +/- 17.8 per hour. These characteristics
      were dose independent, and the Vss and clearance were smaller than those of a
      well characterized PLD comprised of hydrogenated soybean phosphatidylcholine
      (HSPC). At the dose level of 50 mg/m(2), its plasma area under the concentration
      time curve was approximately twice that of HSPC PLD. Attenuation of acute
      toxicity, such as nausea, emesis, and alopecia, was noted in all dose levels.
      However, stomatitis was common from the dose level of 30 mg/m(2), and its
      incidence and severity increased with dosage and became dose limiting at 50
      mg/m(2). A dose of 45 mg/m(2) every 3 weeks was then given in eight patients, and
      the side effects were acceptable. This dose was recommended for Phase II clinical
      trials. Fourteen of 17 patients with a dose level > or = 40 mg/m(2) were
      evaluable for response, but none achieved partial remission. CONCLUSIONS: This
      DSPC PLD had the characteristics of second-generation liposomal drug
      pharmacokinetically and toxicologically. The incidence of severe stomatitis was
      higher than that of HSPC PLD, corresponding to the difference in
      pharmacokinetics. Only limited antitumor activity was observed, although defining
      its therapeutic application will need further Phase II studies. Further
      prolongation of plasma stability of PLD may not be clinically beneficial
      considering the increased stomatitis and the reduced achievable dose intensity.

PMID- 11335911
TI  - Impact of breast carcinoma on African-American women: the Detroit experience.
AB  - BACKGROUND: National and regional population-based data have demonstrated
      substantially worse outcome in African-American patients with breast carcinoma
      when compared with white patients, as well as a younger age distribution among
      African-American patients with breast carcinoma. The extent to which various
      socioeconomic, environmental, lifestyle, and genetic factors interact to account
      for this ethnicity-related disparity in survival is poorly understood. Greater
      than one-half of the inner-city population of Detroit, Michigan is African
      American, and greater metropolitan Detroit has been one of the contributing
      registries for the Surveillance, Epidemiology, and End Results (SEER) program
      since its inception in 1973. The impact of breast carcinoma on African Americans
      in the Detroit area is therefore well documented and provides significant insight
      into the history, epidemiology, and biology of this major public health care
      problem. METHODS: A review of the medical literature published over the past 20
      years regarding African-American patients with breast carcinoma was performed.
      The pertinent findings were summarized in the context of advances made in breast
      carcinoma screening, treatment, and risk reduction during that period. RESULTS:
      The large African-American population of Detroit is a major factor contributing
      to the excessive breast carcinoma mortality rate reported for this city, which is
      one of the highest in the United States. Improvements in early detection of
      breast carcinoma by using screening mammography have been apparent in the earlier
      stage distributions of breast carcinoma observed in both white and African
      American patients; however, progress has lagged substantially for the latter
      group. Detroit SEER registry data also have shown a younger age distribution of
      African-American patients with breast carcinoma and higher rates of estrogen
      receptor negative tumors. Finally, preliminary data from health maintenance
      organizations have suggested improved breast carcinoma outcome for African
      Americans who possess greater socioeconomic benefits, but disparities in disease
      stage at presentation persist. CONCLUSIONS: The diverse Detroit community is
      ideally suited for breast carcinoma screening programs and clinical
      investigations that seek to address and overcome ethnicity-related survival
      disparities and barriers to health care. Findings from these studies can be
      correlated with results from similar projects in other geographic areas.

PMID- 11335912
TI  - Homologies of process and modular elements of embryonic construction.
AB  - There are several signal transduction pathways that integrate embryonic
      development. We find that both within species and between species, these pathways
      constitute homologous modules. The processes, themselves, can be considered
      homologous, just as structures can be considered homologous. Just like vertebrate
      limbs, these pathways are composed of homologous parts (in this case, the
      proteins of the pathway) that are organized in homologous ways. These pathways
      are conserved through evolutionary time, and they undergo descent with
      modification. Such homologies of processes become critical to the discussion of
      evolution and development when we consider (1) that evolution depends on
      heritable changes in development, (2) that development is modular such that
      different modules can change without affecting other modules, (3) that modules
      can be co-opted into new functions, and (4) that modules depend on intercellular
      communication.

PMID- 11335913
TI  - Homology and evolutionary novelty in the deployment of extracellular matrix
      molecules during pigment pattern formation in the salamanders Taricha torosa and
      T. rivularis (Salamandridae).
AB  - Salamander larvae exhibit a diverse array of pigment patterns shortly after
      hatching. Previous studies have identified roles for the extracellular matrix and
      lateral line sensory system in promoting the development of a phylogenetically
      common pattern of horizontal melanophore stripes. In contrast, salamanders in the
      genus Taricha exhibit evolutionarily derived pigment patterns and pattern-forming
      mechanisms. Taricha torosa larvae exhibit compact melanophore stripes that
      develop via redundant, lateral line-independent mechanisms, whereas T. rivularis
      larvae lack stripes and instead have melanophores uniformly distributed over the
      flank. In this study, I test roles for candidate patterning molecules of the
      extracellular matrix in promoting the development of species-specific pigment
      patterns in Taricha. I show that tenascin deposition is negatively correlated
      with melanophore distributions both intraspecifically and interspecifically: this
      matrix molecule is present where melanophores do not localize in T. torosa and is
      absent from these same regions where melanophores are abundant in T. rivularis.
      Embryological manipulations further indicate that transient expression of
      tenascin in a prospective interstripe region of T. torosa reflects a
      phylogenetically conserved effect of lateral line development. Finally, anti
      laminin immunoreactivity is negatively correlated with melanophore distributions
      in T. torosa, and this species exhibits a general retardation of extracellular
      matrix development that may allow persistent, evolutionarily novel melanophore
      motility in this species. Together these findings identify tenascin and laminin,
      or molecules co-regulated with these matrix components, as candidates for
      promoting early larval pigment pattern development in Taricha.

PMID- 11335914
TI  - Alloimmune memory is absent in the Red Sea hydrocoral Millepora dichotoma.
AB  - When two allogeneic colonies of the Red Sea hydrocoral Millepora dichotoma
      (Cnidaria, Hydrozoa) come into tissue contact, one of the genotypes is usually
      overgrown by the other. The directionality and pace of this alloresponse are
      thought to be genetically determined. We established tissue contacts between
      allogeneic colonies in situ in order to elucidate a possible memory component in
      this response. First-set interactions were established from all possible pairwise
      combinations between three colonies in eight replicates per combination.
      Interactions were followed up for 8 weeks. Thereafter, interacting pairs were
      detached and either regrafted near the original contact area to form second-set
      assays or challenged by third party grafts. Additional delayed first-set assays
      was also established. Overgrowth of delayed first-set, second-set, and third
      party grafts was followed again for 8 weeks. The mean overgrowths recorded in the
      second set of the interactions were indistinguishable from the first sets in all
      three colony combinations. A specific alloimmune memory has not been found in
      this cnidarian system as opposed to other cases within the phylum.

PMID- 11335915
TI  - Theory of the growth and evolution of feather shape.
AB  - We present the first explicit theory of the growth of feather shape, defined as
      the outline of a pennaceous feather vane. Based on a reanalysis of data from the
      literature, we propose that the absolute growth rate of the barbs and rachis
      ridges, not the vertical growth rate, is uniform throughout the follicle. The
      growth of feathers is simulated with a mathematical model based on six growth
      parameters: (1) absolute barb and rachis ridge growth rate, (2) angle of helical
      growth of barb ridges, (3) initial barb ridge number, (4) new barb ridge addition
      rate, (5) barb ridge diameter, and (6) the angle of barb ramus expansion
      following emergence from the sheath. The model simulates growth by cell division
      in the follicle collar and, except for the sixth parameter, does not account for
      growth by differentiation in cell size and shape during later keratinization. The
      model can simulate a diversity of feather shapes that correspond closely in shape
      to real feathers, including various contour feathers, asymmetrical feathers, and
      even emarginate primaries. Simulations of feather growth under different
      parameter values demonstrate that each parameter can have substantial,
      independent effects on feather shape. Many parameters also have complex and
      redundant effects on feather shape through their influence on the diameter of the
      follicle, the barb ridge fusion rate, and the internodal distance. Simulated
      isochrones-the loci, or sets, of feather cells of the same age-have the same
      oblique chevron-shaped position in the mature feather as fault bars, which are
      isochronic defects in the barbules created by a disruptions during development.
      Accurate simulation of fault bar shape and position confirms the uniform absolute
      growth rate hypothesis and the general realism of the model. The theory defines a
      six-parameter feather morphospace, and provides many predictions about the
      developmental determination of feather shape that can be tested with detailed
      observations and experiments on developing feathers. This theory also provides
      testable predictions about the changes in developmental mechanisms required to
      evolve different feather shapes to accomplish various functions.

PMID- 11335916
TI  - Lipovitellins derived from two forms of vitellogenin are differentially processed
      during oocyte maturation in haddock (Melanogrammus aeglefinus).
AB  - In the process of cloning vitellogenin (Vtg) cDNAs from haddock (Melanogrammus
      aeglefinus), two related, but distinct, mRNAs were identified. Full-length cDNA
      sequences were determined for both Vtg types (Had1 and Had2), and the deduced
      amino acid sequences were found to be 54% identical to each other and 48-58%
      identical to other teleost Vtgs. To investigate the expression of the two Vtg
      mRNAs, proteins from prehydrated oocytes and fertilized eggs were separated on
      SDS-polyacrylamide gels. Only a single lipovitellin I band was detected in each
      sample, and the egg lipovitellin I was smaller (97 vs. 110 kDa) than the oocyte
      protein, indicative of proteolytic processing during oocyte hydration. Mass
      spectrometric (MALDI-TOFMS and tandem mass spectrometry) analyses of tryptic
      fragments from the haddock oocyte and egg lipovitellin I revealed that the
      lipovitellin I from prehydrated oocytes contained tryptic fragments that matched
      the sequences of both types of Vtg, suggesting that there were two proteins in
      this band, while the egg lipovitellin I contained tryptic fragments that only
      matched the Had1 cDNA sequence, indicating that the Had2 lipovitellin had been
      degraded during hydration. Physiological data from haddock oocytes and eggs
      demonstrate that, as in other marine fish that spawn pelagic eggs, the free amino
      acid content increases during oocyte hydration and apparently contributes to
      hydration by driving the osmotic uptake of water. The correlation of the
      disappearance of one lipovitellin I with the increase of free amino acids in the
      oocyte suggests that this protein is a major source of the free amino acids for
      oocyte hydration.

PMID- 11335918
TI  - Characterisation and expression of Sox9 in the Leopard gecko, Eublepharis
      macularius.
AB  - Since the discovery of the sex-determining gene, Sry, a number of genes have been
      identified which are involved in sex determination and gonadogenesis in mammals.
      Although Sry is known to be the testis-determining factor in mammals, this is not
      the case in non-mammalian vertebrates. Sox9 is another gene that has been shown
      to have a male-specific role in sex determination, but, unlike Sry, Sox9 has been
      shown to be involved in sex determination in mammals, birds, and reptiles. This
      is the first gene to be described that has a conserved role in sex determination
      in species with either chromosomal or environmental sex-determining mechanisms.
      Many reptiles do not have sex chromosomes but exhibit temperature-dependent sex
      determination (TSD). Sox9 has been shown to be expressed in both turtle and
      alligator during gonadogenesis. To determine if Sox9 also has a role in a gecko
      species with TSD, we studied gonadal expression of Sox9 during embryonic
      development of the Leopard gecko (Eublepharis macularius). Gecko Sox9 was found
      to be highly conserved at the nucleotide level when compared to other vertebrate
      species including human, chick, alligator, and turtle. Sox9 was found to be
      expressed in embryos incubated at the male-producing temperature (32.5 degrees C)
      as well as in embryos incubated at the female-producing temperatures (26 and 34
      degrees C), Northern blot analysis showed that Sox9 was expressed at both
      temperatures from morphological stages 31 to 37. mRNA in situ hybridisation on
      isolated urogenital systems showed expression at both female- and male-producing
      temperatures up to stage 36. After this stage, no expression was seen in the
      female gonads but expression remained in the male. These data provide further
      evidence that Sox9 is an essential component of a testis-determining pathway that
      is conserved in species with differing sex-determining mechanisms.

PMID- 11335917
TI  - Isolation of Dlx and Emx gene cognates in an agnathan species, Lampetra japonica,
      and their expression patterns during embryonic and larval development: conserved
      and diversified regulatory patterns of homeobox genes in vertebrate head
      evolution.
AB  - Agnathan cognates of vertebrate homeobox genes, Emx and Dlx, were isolated from
      embryonic cDNA of a Japanese marine lamprey, Lampetra japonica. Analyses of amino
      acid sequences indicated that the Dlx cognate was closely related to the common
      ancestor of gnathostome Dlx1 and Dlx6 groups and termed LjDlx1/6. Southern blot
      analyses could not rule out the possibility that L. japonica possesses more than
      one paralog for both LjDlx1/6 and LjEmx, the lamprey cognate of Emx. Expression
      of LjDlx1/6 was regulated spatially as well as developmentally, and its
      transcripts were mainly found in the craniofacial and pharyngeal mesenchyme and
      in the forebrain. The expression pattern of LjEmx changed dramatically during
      embryogenesis; expression was seen initially in the entire neural tube and
      mesoderm, which were secondarily downregulated, and secondarily in cranial nerve
      ganglia and in the craniofacial mesenchyme. No specific expression of LjEmx was
      seen in the telencephalon. Comparisons of Dlx and Otx gene expression patterns
      suggested a shared neuromeric pattern of the vertebrate brain. Absence of Emx
      expression implied that the patterning of the lamprey telencephalon is not based
      on the tripartite plan that has been presumed in gnathostomes. Expression domains
      of LjDlx1/6 in the upper lip and of LjEmx in the craniofacial mesenchyme were
      peculiar features that have not been known in gnathostomes. Such differences in
      expression pattern may underlie distinct morphogenetic pathway of the mandibular
      arch between the agnathans and gnathostomes.

PMID- 11335932
TI  - Characterization of a novel gene expressed in neuromuscular tissues and
      centrosomes in Caenorhabditis elegans.
AB  - The nematode Caenorhabditis elegans has many advantages for studying gene
      function at the organism level. In particular, completion of the genome
      sequencing has made it feasible to study gene structure and function of both
      known and novel proteins. As a result of a database search for muscle-specific
      genes, a gene F43D9.1 was found which showed muscle-specific expression as
      revealed by the in situ hybridization pattern from the Expressed Sequence Tag
      (EST) database. A homology search of F43D9.1 protein sequences showed no
      significant homology with other known proteins, except that it showed very weak
      sequence similarity with the band 4.1 protein superfamily. Northern blot analysis
      reveals a single transcript 3.7 kb in size which is consistent with the predicted
      gene structure. The expression pattern of F43D9.1 was investigated using the gfp
      reporter gene, and it has shown to be expressed in neuronal cells including
      sensory neurons and interneurons in the head region. To further characterize
      F43D9.1, whole-mount immunostaining was performed with anti-F43D9.1 antibody,
      which showed specific signals in head neurons, body-wall muscle cells, some other
      unidentified neuronal cells, and centrosomes of the dividing cells during
      embryogenesis. Taken together with its predicted membrane topology, we speculate
      that the F43D9.1 gene, which encodes a novel transmembrane protein and contains a
      band 4.1-like domain, may function in neuromuscular cells, and may play an
      important role during cell division in C. elegans.

PMID- 11335933
TI  - Influence of oxidation and crosslinking on oxygen binding properties of mouse
      erythrocytes.
AB  - Different chemical treatments for mouse erythrocyte modification has been used.
      Oxidation treatments with Ascorbate/Fe(3+), a system able to react with
      intracellular proteins, produced a displacement of the O(2) binding equilibrium
      curve to a higher affinity behaviour with loss of the haemoglobin cooperativity
      for oxygen binding. Incubation of mouse erythrocytes with diamide showed that at
      low reagent concentration (0.8 mM) no modification on oxygen binding equilibrium
      curves was observed. At higher reagent concentration (2.0 mM), an increased
      affinity and a disappearance of the cooperative behaviour can be observed.
      Additionally, crosslinking reactions on mouse erythrocytes with band 3
      crosslinkers seemed to affect oxygen binding properties when used at a
      crosslinker concentration of 5 mM. Oxyhaemoglobin levels in crosslinked and
      diamide-treated erythrocytes are similar to those found in control cells. In
      contrast, ascorbate/Fe(3+) treatments produced an increment in the proportion of
      methaemoglobin, decreasing the oxyhaemoglobin levels in these oxidized
      erythrocytes.

PMID- 11335934
TI  - Eicosapentaenoic acid and docosahexaenoic acid effects on tumour mitochondrial
      metabolism, acyl CoA metabolism and cell proliferation.
AB  - In order to investigate the effects of high-fat diets rich in eicosapentaenoic
      acid (EPA) and docosahexaenoic acid (DHA), Wistar rats bearing subcutaneous
      implants of the Walker 256 tumour were fed pelleted chow containing low DHA/EPA
      or high DHA/EPA. The presence of n-3 polyunsaturated fatty acids (PUFAs) led to a
      marked suppression (35-46%) of tumour growth over a 12 day period. Both the whole
      tumour homogenate and the Percoll-purified mitochondrial fraction presented
      significant changes in fatty acid composition. The levels of EPA increased in
      both n-3 dietary groups while the levels of DHA increased only in the high
      DHA/EPA group, in comparison with the control chow-fed group. The presence of n-3
      PUFAs led to an increase in mitochondrial acyl CoA synthetase activity, but
      neither the cytoplasmic acyl CoA content nor the n-3 fatty acid composition of
      the cytoplasmic acyl CoAs was altered by the diet. The content of thiobarbituric
      acid-reactive substances (TBARS) was increased in the low DHA/EPA group but was
      unchanged in the high DHA/EPA group. In vitro studies with the Walker 256 cell
      line showed a 46% decrease in cell growth in the presence of either EPA or DHA
      which was accompanied by a large decrease in the measured mitochondrial membrane
      potential. The TBARS content was increased only in the EPA-exposed cells. Cell
      cycle analysis identified a decrease in G0-G1 phase cells and an increase in G2-M
      phase cells and apoptotic cells, for both EPA and DHA-exposed cells. The data
      show that the presence of n-3 PUFAs in the diet is able to significantly after
      the growth rate of the Walker 256 tumour. The involvement of changes in
      mitochondrial membrane composition and membrane potential have been indicated for
      both EPA and DHA, while changes in lipid peroxidation have been identified in the
      presence of EPA but not of DHA.

PMID- 11335935
TI  - Pancreatic fate of a (125)I-labelled mouse monoclonal antibody directed against
      pancreatic B-cell surface ganglioside(s) in control and diabetic rats.
AB  - The possible use of a mouse monoclonal antibody directed against rat pancreatic B
      cell surface ganglioside(s) and labelled with radioactive iodine for selective
      imaging of the endocrine pancreas by a non-invasive procedure was investigated by
      following its pancreatic fate in experiments conducted either in vitro by
      incubation of rat isolated pancreatic islets, acinar tissue and pancreatic pieces
      or in vivo after intravenous injection of the (125)I-labelled antibodies
      ([(125)I]gamma-G). Although the binding of [(125)I]gamma-G per microg protein was
      about one order of magnitude higher in isolated islets than in acinar tissue, no
      significant difference was detected when comparing pancreatic pieces or isolated
      islets from control animals and rats rendered diabetic by one or two prior
      administrations of streptozotocin (STZ rats). Likewise, except in one set of
      experiments, no significant difference was found between control animals and STZ
      rats, when measuring the radioactive content of the pancreatic gland, relative to
      that of plasma, 1-4 days after the intravenous injection of [(125)I]gamma-G.
      These findings indicate that under the present experimental conditions, the mouse
      monoclonal antibody labelled with radioactive iodine does not appear to be a
      promising tool for selective imaging of the endocrine pancreas, e.g. by single
      photon emission computerized tomography.

PMID- 11335936
TI  - The uncoupling effect of the nonsteroidal anti-inflammatory drug nimesulide in
      liver mitochondria from adjuvant-induced arthritic rats.
AB  - The aim of the present study was to evaluate the changes caused by adjuvant
      induced arthritis in liver mitochondria and to investigate the effects of the
      nonsteroidal anti-inflammatory drug nimesulide. The main alterations observed in
      liver mitochondria from arthritic rats were: higher rates of state IV and state
      III respiration with beta-hydroxybutyrate as substrate; reduced respiratory
      control ratio and impaired capacity for swelling dependent on beta
      hydroxybutyrate oxidation. No alterations were found in the activities of NADH
      oxidase and ATPase. Nimesulide produced: (1) stimulation of state IV respiration;
      (2) decrease in the ADP/O ratio and in the respiratory control ratio; (3)
      stimulation of ATPase activity of intact mitochondria; (4) inhibition of swelling
      driven by the oxidation of beta-hydroxybutyrate; (5) induction of passive
      swelling due to NH(3)/NH(4)+ redistribution. The activity of NADH oxidase was
      insensitive to nimesulide. Mitochondria from arthritic rats showed higher
      sensitivity to nimesulide regarding respiratory activity. The results of this
      work allow us to conclude that adjuvant-induced arthritis leads to quantitative
      changes in some mitochondrial functions and in the sensitivity to nimesulide.
      Direct evidence that nimesulide acts as an uncoupler was also presented. Since
      nimesulide was active in liver mitochondria at therapeutic levels, the impairment
      of energy metabolism could lead to disturbances in the liver responses to
      inflammation, a fact that should be considered in therapeutic intervention.

PMID- 11335937
TI  - The effects of some antioxidant vitamin- and trace element-supplemented diets on
      activities of SOD, CAT, GSH-Px and LPO levels in chicken tissues.
AB  - The effect of diets containing antioxidant vitamins and trace elements on chicken
      tissue activities of SOD, CAT, GSH-Px and of LPO levels was investigated.
      Chickens, 45 weeks of age were divided into six groups: control group, Cu group
      (13.2 mg Cu kg(-1) diet); Se group (0.07 mg Se kg(-l) diet); vitamin E group (70
      mg DL-alpha-tocopherol acetate kg(-1) diet) and a constant level vitamin C, 200
      mg kg(-1) diet); vitamin A group (240 mg retinol acetate kg(-1) diet) and vitamin
      C group (500 mg ascorbic acid kg(-1) diet). Significant variation of these
      antioxidant enzyme activities and LPO levels according to gender was demonstrated
      statistically. In the Cu group, CuZnSOD activity in the liver, erythrocyte,
      kidney and heart significantly increased by 75, 40, 12, 12% respectively
      (P<0.05). MnSOD activity in the heart, liver, kidney and brain of the vitamin C
      and in the heart of Cu group were found to be increased by approximately 15%,
      while in liver tissue of the Cu group it was reduced by 19% (P<0.05). GSH-Px
      activities in the Se, vitamin E and C groups were significantly increased,
      conversely LPO levels decreased (P<0.001). CAT activities in the liver and heart
      of the vitamin C group were significantly decreased (by 32%), but in kidney
      tissue only that of the Cu group was increased from 30.2 +/- 4.767 to 144.49 +/-
      6.93 U mg(-1) P<0.001. The resistance to stress of the vitamin E and C groups,
      which had significantly increased activities of antioxidant enzymes and decreased
      lipid peroxide levels, were determined in 60% moisture medium at 45 degrees C.

PMID- 11335938
TI  - New methods for the isolation of skeletal muscle sarcolemma and sarcoplasmic
      reticulum allowing a comparison between the mammalian and amphibian beta(2)
      adrenergic receptors and calcium pumps.
AB  - New methods were established for the rapid and simultaneous isolation of multiple
      sarcolemmal and sarcoplasmic reticular fractions from very small amounts (0.25
      2.0 g) of skeletal muscle. Thebeta(2)-adrenergic receptor and calcium transport
      systems were used as indices of purity and functional integrity as well as being
      the focal points of the study. These methods were found to be suitable for the
      special needs of small tissue samples, allowed rapid preparation and were
      appropriate for skeletal muscle from various species, frogs to mammals. The
      sarcolemmalbeta(2)-adrenergic receptor was expressed in frogs and mammals at
      similar levels of expression (336-454 fmol. x mg(-1)). The calcium pump was also
      present in sarcolemmal and sarcoplasmic reticular fractions in all species but
      notable species differences were found. In sarcolemmal fractions, while calcium
      binding was uniformly low (<1 nmol. x mg(-1)), oxalate stimulation was variable:
      low in frogs ( approximately 1.05-fold) high in mammals (120-450-fold). In
      sarcoplasmic reticular fractions, calcium binding was low in frogs (4-9 nmol. x
      mg(-1)) and much higher in mammals (322-383 nmol. x mg(-1)); oxalate stimulated
      calcium transport to a much greater extent in frogs (<70-fold) than in mammals
      (1.6-2-fold). It is concluded that thebeta(2)-adrenergic receptor appears to be
      strongly conserved in skeletal muscle while the use of calcium pumps evolves from
      reliance in Amphibia on the sarcoplasmic reticular calcium pump to the use in
      Mammalia of calcium pumps from both the sarcoplasmic reticulum and the plasma
      membrane.

PMID- 11335939
TI  - Characterization of sarcolemma and sarcoplasmic reticulum isolated from skeletal
      muscle of the freeze tolerant wood frog, Rana sylvatica: the beta(2)-adrenergic
      receptor and calcium transport systems in control, frozen and thawed states.
AB  - In freeze tolerant wood frog Rana sylvatica, the freeze-induced liberation of
      glucose plays a critical role in survival in response to sub-zero temperature
      exposure. We have shown that the glycaemic response is linked to selective
      changes in the expression of hepatic adrenergic receptors through which
      catecholamines act to produce their hepatic glycogenolytic effects. The purpose
      of the present study was to determine if skeletal muscle, another catecholamine
      sensitive tissue with glycogenolytic potential, displayed similar or different
      changes. In order to achieve these objectives, skeletal muscle derived from Rana
      sylvatica was studied in control, frozen and thawed states. In isolated
      sarcolemmal fractions, freezing effected an 88% decrease in beta(2)-adrenergic
      receptor expression but was without effect on the calcium pump; while thawing
      resulted in a recovery of the beta(2)-adrenergic receptor to 60% of control
      levels and a 2.4-fold increase in calcium transport. In isolated sarcoplasmic
      reticular fractions, freezing effected a 52% decrease in calcium binding and a
      92% decrease in oxalate-stimulated calcium uptake; while thawing elicited partial
      normalization to control levels to 70% with respect to calcium binding and to 47%
      with respect to calcium uptake. Freezing and thawing were associated with
      increases and decreases, receptively, in blood glucose levels but were without
      effect on skeletal muscle glycogen content. Thus these muscle changes in Rana
      sylvatica in freezing and thawing are not linked to glycogen breakdown, are
      different from those previously seen in liver, and may provide a role in recovery
      of muscle function during thawing by protecting glycogen stores for contraction
      and maximizing extracellular calcium for excitation-contraction coupling in the
      frozen state. The involvement of thyroid hormone in triggering these muscle
      changes is discussed.

PMID- 11335940
TI  - Stage-dependent and alternative splicing of sGnRH messengers in rainbow trout
      testis during spermatogenesis.
AB  - The gonadotropin releasing hormone (GnRH) has long been considered as a
      neuropeptide involved in the control of the reproductive cycle. However, the
      presence of GnRH and its receptors in various tissues, including ovary and
      testis, suggests a role as autocrine/paracrine factor. In the present study, we
      report the expression of the sGnRH-1 and sGnRH-2 genes encoding salmon GnRH in
      rainbow trout testis throughout testicular development and spermatogenesis. We
      demonstrate that both sGnRH mRNA are expressed prior of sexual differentiation.
      In adult, northern blot analysis indicates that sGnRH-2 transcripts are expressed
      in the testis at higher levels than sGnRH-1 messengers. Moreover, we observed
      that the expression of sGnRH-2, and not sGnRH-1, messengers was stage-dependent.
      sGnRH-2 mRNA expression decreases at the onset and progressively rebounds at the
      end of spermatogenesis. In addition, we demonstrate that a complex stage
      dependent and differential splicing of the sGnRH-2 messengers occurs throughout
      spermatogenesis. We isolated five transcripts corresponding to sGnRH-2
      messengers. Two of them may encode a novel and shortened GnRH-associated peptide
      containing 18 residues instead of 46. Our data provide new insight in the
      putative role of GnRH and GAP peptides as autocrine/paracrine factors of
      spermatogenesis.

PMID- 11335941
TI  - Novel alternatively spliced mRNA (1c) of the protein kinase A RI&alpha; subunit
      is implicated in haploid germ cell specific expression.
AB  - By using 5' RACE on rat testis cDNA we identified three alternatively spliced
      mRNAs of the RIalpha subunit of cAMP-dependent protein kinase that differed in
      their 5' untranslated regions. Two of these 5'-regions showed similarity with the
      human RIalpha exons 1a and 1b, while the third (1c) constituted a novel mRNA
      splice variant. Northern blot analysis showed that the 1c mRNA was specifically
      expressed in testis and only in postmeiotic germ cells. In contrast, the RIalpha
      1b and RIalpha 1a mRNAs were present both in premeiotic germ cells and somatic
      cells of the testis, and the expression of both RIalpha 1a and 1b mRNAs were
      stimulated by cAMP in Sertoli cells. In sperm, the RIalpha protein was expressed
      after meiosis, and targeted to various subcellular structures via anchoring
      proteins. The RIalpha 1c haploid-specific mRNA, therefore, may be important for
      the regulation of RIalpha expression in sperm.

PMID- 11335942
TI  - Involving AP-2 transcription factor in connexin 26 up-regulation during pregnancy
      and lactation.
AB  - Gap junction connexin 26 (Cx26) is up-regulated in mammary epithelial cells
      during pregnancy and lactation. To understand the transcriptional regulation of
      Cx26, we identified a protected DNase I footprint region (-140 to -113) in the
      rat Cx26 promoter. This rCx26 Promoter Footprinting Region, or CPFR, contains an
      Sp binding site (CCGCCC) overlapping with an AP-2 binding site (GCCCGCGGC), and
      is evolutionarily conserved. Nuclear extracts from rat mammary glands and human
      MCF-10 mammary epithelial cells formed protein-DNA complexes with the labeled
      CPFR probe in the electrophoretic mobility shift assay (EMSA), and these
      complexes were markedly enhanced during pregnancy and lactation. Antibody
      supershift analysis further identified the presence of Sp1, Sp3, and AP-2 in
      these binding complexes. Human mammary epithelial MCF-10A and MCF-12A cells were
      transiently transfected with chimeric mutant rCx26 promoter/luciferase reporter
      constructs, and luciferase activities measured. Mutations along the CPFR fragment
      drastically reduced the promoter activity, specially at the Sp/AP-2 overlapping
      site. Cotransfection of AP-2 with rCx26 promoter/reporter constructs into MCF-10
      cells markedly induced the reporter activity. These data infer that AP-2, along
      with previously reported Sp transcription factors, is involved in the up
      regulation of Cx26 gene during pregnancy and lactation.

PMID- 11335943
TI  - Germ cell specific promoter drives ectopic transgene expression during
      embryogenesis.
AB  - In this study, we used the male germ cell-specific phosphoglycerate kinase 2
      (Pgk2) promoter to generate Pgk2Cre transgenic mice to allow investigation of
      genes critically involved in meiosis. The Pgk2 promoter had been used previously
      to target transgene expression to spermatocytes and spermatids in several
      laboratories including ours. In several Cre targeting experiments using other
      promoters, ectopic Cre expression had been observed, but the timing and extent of
      this expression was not analyzed. We demonstrate that in adult mice the Pgk2Cre
      transgene is expressed specifically in spermatocytes and spermatids, as expected.
      However, in offspring from matings of Pgk2Cre mice and an H19loxP indicator
      strain, we discovered that recombination events had occurred in several, but not
      all, tissues to varying extents. The lacZ-loxP transgenic indicator strain was
      next used to uncover ectopic Cre expression even in single cells, which indicated
      that the Pgk2Cre transgene is expressed between days 11 and 15 during
      embryogenesis in several tissues and organs. Using an RT PCR assay we were unable
      to detect endogenous Pgk2 mRNA during embryogenesis or in adult tissues other
      than testis. In conclusion, the Pgk2 promoter is a valid choice for targeting
      gene expression to meiotic male germ cells, since transient ectopic expression is
      unlikely to have a discernable effect in most studies, but it may be
      inappropriate for utilization with Cre recombinase.

PMID- 11335944
TI  - Assessment of metabolism of equine morulae and blastocysts.
AB  - Nutrient uptakes and metabolite production by equine morula and blastocyst stage
      embryos were determined by non-invasive microfluorometry. Equine morula took up
      equal amounts of both pyruvate and glucose. However, at the early blastocyst
      there was a small increase in glucose uptake and, by the expanded blastocyst
      stage, glucose was the predominant nutrient. Expanded blastocysts took up five
      times more glucose than pyruvate. Expanded blastocysts exhibited an exponential
      increase in glucose uptake and lactate production with respect to both diameter
      and surface area. As less than 50% of the glucose was accounted for by lactate
      production, the equine blastocyst appears to have a significant capacity to
      oxidize glucose. Embryos with a higher morphological grade consumed more
      nutrients than those with a poorer morphology. However, there was a large range
      in nutrient consumption within the highest grade blastocysts. This suggests that
      nutrient uptake may be useful as a viability marker of equine blastocysts.

PMID- 11335945
TI  - Full term development of rabbit oocytes fertilized by intracytoplasmic sperm
      injection.
AB  - Intracytoplasmic sperm injection (ICSI) has been applied successfully in the
      treatment of male infertility in humans and in fertilization research in mice.
      However, the technique has had limited success in producing offspring in other
      species including the rabbit. The aim of this research was to test the in vitro
      and in vivo developmental of rabbit oocytes after ICSI. Sperm used for ICSI were
      collected from mature Dutch Belted buck and washed 2-3 times with PBS +0.1%
      polyvinyl alcohol (PVA) and then mixed with 10% polyvinyl pyrrolidone (PVP) prior
      to microinjection. Oocytes were collected from superovulated does 14-15 hr after
      hCG injection and were fertilized by microinjection of a single sperm into the
      ooplasm of each oocyte without additional activation treatment. After ICSI, the
      presumed zygotes were either cultured in KSOM +0.3% BSA for 4 days or transferred
      into oviducts of recipient does at the pronuclear or 2-cell stage. A high
      percentage of fertilization (78%, n = 114) and blastocyst development (39%) was
      obtained after ICSI. Control oocytes, receiving a sham injection, exhibited a
      lower activation rate (31%, n = 51) and were unable to develop to the blastocyst
      stage, suggesting that the blastocysts developed following ICSI were derived from
      successful fertilization rather than parthenogenetic development. A total of 113
      embryos were transferred to six recipient does. Two recipients became pregnant
      and delivered seven live young. Our results demonstrated that rabbit oocytes can
      be successfully fertilized and activated by ICSI and can result in the birth of
      live offspring.

PMID- 11335946
TI  - Protection against reactive oxygen species during mouse preimplantation embryo
      development: role of EDTA, oxygen tension, catalase, superoxide dismutase and
      pyruvate.
AB  - Oxidative damage due to the production of reactive oxygen species (ROS) is one of
      a number of culture-induced stresses which may compromise preimplantation embryo
      development in vitro. Ethylenediaminetetraacetic acid (EDTA), reduced oxygen
      tension, superoxide dismutase (SOD) and catalase (CAT) offer protection against
      oxidative stress, but few attempts have been made to determine which of these
      agents, or which combination, is the most effective. In particular, no systematic
      investigation of their actions and interactions has been made using a
      multifactorial experimental design. Murine zygotes were cultured in the presence
      or absence of 10 miccroM EDTA, SOD (100-7,000 U/ml) and CAT (50-100 U/ml) at
      atmospheric (20%) and reduced (5%) oxygen tensions. Blastocyst formation and
      hatching rates (at various time points), and cell numbers were recorded, whilst
      parallel groups of embryos had their consumption of pyruvate, a hydrogen peroxide
      scavenger, measured. All parameters interacted significantly and affected
      blastocyst formation, hatching rate and cell numbers but the effect of EDTA was
      the most pronounced. There were beneficial effects of 5% O2, CAT and SOD, while
      20% O2 had a deleterious effect on development. EDTA improved blastocyst
      formation and hatching rates but paradoxically led to a reduction in cell number.
      5% O2 was the next most significant parameter to enhance embryo development and
      also increased cell numbers. No differences in pyruvate uptake were apparent
      between the various treatment groups. The results suggest that embryo culture in
      EDTA-free medium under 5% O2 provides the most practical and physiological
      conditions for in vitro murine embryo culture.

PMID- 11335947
TI  - Biogenesis of lysosomes in marshall cells and in cells of the male reproductive
      system.
AB  - The mechanism of plasma membrane trafficking and degradation is still poorly
      understood. This investigation deals with the biogenesis of lysosomes during
      endocytic flow in Marshall cells and in various cell types of the male
      reproductive system. Marshall cells were exposed to ammonium chloride (NH4Cl) and
      leupeptin after labeling with cationic ferritin. In some experiments, the treated
      cells were immunogold labeled with anti-prosaposin antibody. NH4Cl and leupeptin
      are lysosomotropic agents that affect the endosomal-lysosomal progression.
      Testes, efferent ducts and epididymis from mouse mutants with defects affecting
      plasma membrane degradation were also used to analyze this process. NH4Cl
      produced a retention of cationic ferritin in endosomes and hindered the
      endosomal/lysosomal progression. Leupeptin did not affect this process. NH4Cl
      decreased the labeling of prosaposin in endosomes and lysosomes, while leupeptin
      increased the labeling of prosaposin in lysosomes. The number of lysosomes per
      cytoplasmic area was higher in treated cells than in controls. These findings
      suggest that leupeptin affected lysosomes whereas NH4Cl affected both endosomes
      and lysosomes. The endosomal and lysosomal accumulation of prosaposin induced by
      the treatment with NH4Cl and leupeptin indicated that the site of entry of
      prosaposinwas both the lysosome and endosome. Electron microscopy (EM) of tissues
      from mouse mutants with defects affecting plasma membrane degradation
      substantiated these observations. The EM analysis revealed a selective
      accumulation of multivesicular bodies (MVBs) and the disappearance of lysosomes,
      in testicular fibroblasts, nonciliated cells of the efferent ducts and principal
      cells of the epididymis, suggesting that MVBs are precursors of lysosomes. IN
      CONCLUSION: (1) endosomes and MVBs are a required steps for degradation of
      membranes; (2) endosomes and MVBs are precursors of lysosomes; and (3) endosomes,
      MVBs, and lysosomes appear to be transient organelles.

PMID- 11335948
TI  - Synaptic pattern of sex complements and sperm head malformation in X-autosome
      translocation carrier bulls.
AB  - Testicular activity and semen characteristics of bulls carrying an X-autosome
      translocation t(Xp +;23q-) revealed all stages of spermatogenesis although their
      semen consisted of few and, exclusively, of malformed spermatozoa. Chromosome
      painting on metaphase spreads of their mother and synaptonemal complex analysis
      on these and normal bulls were carried out to test whether the location and
      meiotic pairing behaviour of the rearranged segments could have contributed to
      the sperm head malformation and oligospermia in our X-autosome translocation (X
      AT) carrier bulls. Spermatocytes of X-AT carriers displayed the rearranged
      chromosomes in a univalent-trivalent association, with 23q- always remaining as a
      univalent and Xp + in synapsis with normal chromosome 23 and the Y chromosome.
      Chromosome painting studies to test whether the total absence of meiocytes
      showing a quadrivalent is due to the non-reciprocal nature of this translocation,
      identified Xp sequence homology with the distal end of 23q- confirming its
      relocation to the terminal segment of 23q-. Our synaptonemal complex analyses
      also confirmed that the bovine pseudo-autosomal region (PAR) is at the distal
      ends of Xq and Yp and further revealed that over 85% of spermatocytes of X-AT
      carriers (and up to 13% of spermatocytes of normal bulls) sustain a Y-axis break
      adjacent to the PAR. Although the exact cause of a Y-axis break in bovine
      spermatocytes is not known at present, we believe that the break and possible
      loss of Yq in such high proportions of spermatocytes of X-AT carriers could have
      contributed to the sperm head malformation and oligospermia in our X-AT carrier
      bulls.

PMID- 11335949
TI  - p62/p56 are cortical granule proteins that contribute to formation of the
      cortical granule envelope and play a role in mammalian preimplantation
      development.
AB  - The purpose of this study was to identify specific cortical granule protein(s)
      that form the cortical granule envelope and examine their role(s) in
      fertilization and preimplantation development. The polyclonal antibody A-BL2 was
      used to show that the cortical granules of mice, rats, hamsters, cows, and pigs
      contain a pair of proteins designated p62/p56. These proteins are released from
      hamster cortical granules at fertilization and contribute to formation of the
      cortical granule envelope, an extracellular matrix present in the perivitelline
      space of fertilized mammalian oocytes. P62/p56 were present in the cortical
      granule envelope throughout preimplantation development and were found in
      blastomere cortices of 4-cell to blastocyst stage embryos. Hamster oocytes
      fertilized in vivo in the presence of A-BL2 were all monospermic, suggesting that
      p62/p56 do not function in blocking polyspermy. Likewise treatment of morula to
      blastocyst stage hamster embryos with A-BL2 had no effect on the implantation of
      blastocysts. However, cleavage divisions were inhibited in vivo in a dose
      dependent manner when fertilized oocytes or 2-cell embryos were treated with A
      BL2. Inhibition of cell division was more pronounced in 2-cell embryos than in
      fertilized oocytes. This study identifies p62/p56 as cortical granule proteins
      that contribute to the formation of the cortical granule envelope and further
      supports the idea that after their release at fertilization, p62/p56 function in
      regulating preimplantation development at the level of oocyte and blastomere
      cleavage.

PMID- 11335950
TI  - Comparison by restriction fragment differential display RT-PCR of gene expression
      pattern in bovine oocytes matured in the presence or absence of fetal calf serum.
AB  - A novel restriction fragment differential display (RFDD) RT-PCR has been used to
      compare patterns of mRNA expression in bovine oocytes matured in vitro in the
      presence (10%) or absence of fetal calf serum (FCS). Total RNA extracted from
      matured and denuded oocytes was processed using display Profile kit (Display
      System Biotech). RFDD RT-PCR products were separated on 6% polyacrylamide gel and
      analyzed using a Storm 860 scanner. Selected bands representing potentially
      differentially expressed fragments were excised from the gel and re-amplified. Re
      amplified fragments with size matched to the original fragment were cloned into
      the TA vector and sequenced. Initially, 10 and 15 differentially expressed
      fragments were isolated from oocytes matured in the presence and absence of FCS,
      respectively. Eight out of 10 and 10 out of 15 fragments were re-amplified
      successfully as evidenced by size similarity to the original fragments. Finally,
      the size of six inserts sequenced from each group matched the size of
      corresponding original as well as re-amplified fragments. Sequence comparison
      search revealed similarity of some isolated fragments to 18s ribosomal RNA,
      bovine apolipoprotein A-I, bovine mitochondrion DNA, human CGI-79 mRNA, human Ab1
      interactor protein, and bovine satellite DNA. The other sequenced fragments may
      represent novel genes. We showed that RFDD RT-PCR can be effectively applied to
      contrast gene expression pattern in bovine oocytes and that presence or absence
      of FCS during maturation interval affects gene expression pattern in matured
      bovine oocytes.

PMID- 11335951
TI  - Progesterone induces activation in Octopus vulgaris spermatozoa.
AB  - The purpose of the present study was to determine whether Octopus vulgaris
      spermatozoa are activated by progesterone stimulation. Spermatozoa were collected
      from the spermatophores in the Needham's sac of the male (MS) and from the
      spermathecae of oviducal glands of the female (FS). We used transmission (TEM)
      and scanning (SEM) electron microscopy to study the morphology of untreated, Ca2+
      ionophore A23187 and progesterone-treated MS spermatozoa, and untreated FS
      spermatozoa. We showed that ionophore and progesterone stimulation of MS
      spermatozoa induce breakdown of the membranes overlapping the acrosomal region,
      exposing the spiralized acrosome. These modifications resemble the acrosome
      reaction observed in other species. FS stored in the spermathecae did not show
      the membranes covering the acrosomal region present in the MS spermatozoa. When
      ionophore and progesterone treatments were performed in Ca2+-free artificial sea
      water, no changes were observed, suggesting the role of external calcium in
      modifying membrane morphology. Lectin studies showed a different fluorescence
      distribution and membrane arrangement of FS-untreated spermatozoa with respect to
      the MS, suggesting that spermatozoa transferred in the female genital tract after
      mating, are stored in a pre-activated state. The plasma membrane of the untreated
      MS and FS spermatozoa was labelled with Progesterone-BSA-FITC, indicating the
      presence of plasma membrane progesterone receptor. Taken together these data
      suggest that progesterone induces an acrosome- like reaction in MS spermatozoa
      similar to that induced by calcium elevation. In addition progesterone may play a
      role in the pre-activation of spermatozoa stored in the female tract, further
      supporting the hypothesized parallelism between cephalopods and vertebrates.

PMID- 11335952
TI  - Mitogen activated protein kinase plays a significant role in metaphase II arrest,
      spindle morphology, and maintenance of maturation promoting factor activity in
      bovine oocytes.
AB  - Mammalian oocytes are arrested at the G2/M transition of the first meiotic
      division from which, after reaching full size and subsequent to an LH surge, they
      undergo final maturation. Oocyte maturation, which involves germinal vesicle
      breakdown, progression through metaphase I (MI), and arrest at MII, is triggered
      and regulated by the coordinated action of two kinases, maturation promoting
      factor (MPF) and mitogen activated protein kinase (MAPK). The importance of the
      role of MPF in mammalian oocyte maturation is well established, while the role of
      MAPK, although well understood in mouse oocytes, has not been fully elucidated in
      oocytes of large domestic species, especially bovine oocytes. Here we show that
      injection of MKP-1 mRNA, which encodes a dual specificity MAPK phosphatase, into
      germinal vesicle stage bovine oocytes prevents the activation of MAPK during
      maturation. Despite the lack of MAPK activity, MKP-1-injected oocytes resume and
      progress through meiosis, although they are unable to arrest at MII stage and, by
      22-26-hour post-maturation, exhibit decondensed pronucleus-like chromatin, a
      clear sign of parthenogenetic activation. MKP-1-injected bovine oocytes exhibit
      normal activation of MPF activity; however, by 18-hour post-maturation, MPF
      activity starts to decline and by 22-26 hr MPF activity is absent. MKP-1-injected
      oocytes also show disorganized MII spindles with poorly aligned chromosomes. In
      summary, our results demonstrate that in bovine oocytes MAPK activity is required
      for MII arrest, maintenance of MPF activity, and spindle organization.

PMID- 11335953
TI  - Prostasome-like particles are involved in the transfer of P25b from the bovine
      epididymal fluid to the sperm surface.
AB  - In bulls, P25b is a sperm protein associated with the plasma membrane covering
      the acrosome. The amount of P25b bound to a constant number of spermatozoa varies
      from one individual to the other, low levels being associated with bull
      subfertility. In this study, we describe the epididymal origin of P25b using
      Western blot analysis. Whereas P25b was undetectable on caput spermatozoa, the
      amount of P25b associated to a constant number of spermatozoa increases from the
      corpus to the cauda. Prostasome-like particles were prepared by
      ultracentrifugation of epididymal fluid. P25b appears to be also associated with
      those membranous vesicles in increasing amounts along the epididymis. P25b is
      anchored to the plasma membrane of spermatozoa through glycosylphosphatidyl
      inositol as shown by the ability of phospholipase C. but not of high salt
      treatment, to release P25b. Coincubation experiments revealed that prostasome
      like particles are able to transfer P25b to spermatozoa, this process being more
      efficient at slightly acidic pH. P25b thus appears to be a marker of sperm
      epididymal maturation in bulls.

PMID- 11335954
TI  - Accuracy evaluation of a CAS system: laboratory protocol and results with 6D
      localizers, and clinical experiences in otorhinolaryngology.
AB  - OBJECTIVES: The objective of the study reported in this article was to evaluate
      (1) localizer inaccuracies, one of the major sources of errors in Computer
      Assisted Surgery (CAS) systems, and (2) the final errors obtained using surface
      based registration in ear, nose, and throat (ENT) surgery. These objectives were
      met through (1) a technical evaluation of the accuracy and usability of several
      optical localizers under laboratory test conditions, and (2) a clinical measure
      of the global errors obtained when using a CAS system including one of the
      standard localizer systems (Flashpoint 5000) in Functional Endoscopic Sinus
      Surgery (FESS). PATIENTS AND METHODS: The technical evaluation of localizers
      consisted of series of geometric tests on four commercial systems. Clinical
      evaluation included the development of a laboratory CAS system using a
      markerless, skin surface registration method. This was based on a standard
      optical digitizing system (Flashpoint 5000), which eliminates the need for the
      second CT scan, which is normally performed specifically to process the position
      of the fiducial markers. Global accuracy was then evaluated on 20 patients by
      subjective and visual comparison when placing a calibrated pointer on anatomical
      landmarks. RESULTS: The results of the technical study indicate that the four
      commercial systems tested have levels of inaccuracy deemed acceptable for most
      CAS applications, including ENT surgery. The clinical study obtained a
      registration and calibration accuracy of less than 1.5 mm in 89.2% (SD = 0.20 mm)
      of the cases studied. Our markerless skin surface points registration method is
      reliable, and allows patient head movements during the procedure. The accuracy
      tests performed show that this type of system can be used for ENT surgery with
      satisfaction. CONCLUSION: CAS systems enable the surgeon to have a more thorough
      understanding of the complicated anatomy of paranasal sinuses, and may be
      especially helpful in revision surgery when normal anatomic landmarks are
      lacking. Further studies are necessary in FESS to improve the CAS systems that
      are currently available, and to determine whether these systems can minimize the
      overall risk of complications.

PMID- 11335955
TI  - Prostate biopsy protocols: 3D visualization-based evaluation and clinical
      correlation.
AB  - OBJECTIVES: Systematic needle core biopsy is commonly used for the diagnosis of
      prostate cancer by urologists worldwide. As accurate and early diagnosis will
      result in more and better options for treatment, it is critical that the best
      possible protocols for biopsy be used clinically. In this study, we develop three
      dimensional (3D) modeling and simulation technologies to evaluate most of the
      biopsy protocols in current clinical use, and correlate the results with those
      from clinical cases. MATERIALS AND METHODS: Using deformable modeling techniques,
      3D computerized prostate surface models were reconstructed from step-sectioned,
      whole-mounted radical prostatectomy specimens with localized prostate cancer. A
      3D computer simulation system was developed to accurately depict the anatomy of
      the prostate and all individual tumor foci. A user-friendly interface was
      developed in the system so that a physician can easily and interactively use it
      for prostate needle core biopsy. A total of 281 prostate models were
      reconstructed, and 18 biopsies were performed by a urologist on each model to
      determine the detection rates of seven different biopsy protocols. Clinical
      biopsies from 35 patient cases were also reviewed and correlated with the
      simulation results. RESULTS: The most commonly used sextant biopsy had only a
      71.5% detection rate, while rates for the 10-pattern and 12-pattern protocols
      were much higher (96.4% and 97.2%, respectively). Even the lateral 4-pattern
      protocol performed better than the sextant protocol, with a detection rate of
      89.3%. The lateral sextant biopsy protocol (using sites similar to, but more
      lateral than, those in the sextant protocol) achieved a rate of 92.5%. Although
      the rate of the 14-pattern biopsy was a little higher (97.5%), it used four more
      biopsies to achieve this increase, which, according to McNemar's test, is not
      statistically significant when compared to results with the 10-pattern protocol.
      The 5-region protocol, which uses 12 biopsies, had a detection rate of 89.7%.
      Transition zone and seminal vesicle biopsies did not result in a significantly
      increased detection rate when added to the patterns above. The clinical
      correlation also confirmed that the 10-pattern protocol was significantly
      superior to the traditional sextant biopsy pattern. CONCLUSIONS: The 10-pattern
      biopsy protocol was the most optimized among all the protocols evaluated. This
      protocol supplemented the sextant biopsy protocol with four more lateral biopsies
      in the mid and apical sites on both sides.

PMID- 11335956
TI  - Interactive navigation system for shock wave applications.
AB  - The latest generation of shock wave lithotripters, with therapy heads mounted on
      articulated arms, have found widespread application in the treatment of
      orthopedic diseases. Currently, integration of an ultrasound probe in the therapy
      head is the dominant modality for positioning the shock wave focus on the
      treatment area. For orthopedic applications, however, X-ray imaging is often
      preferred. This article describes a new method to locate the therapy head of a
      lithotripter. In the first step, the surgeon positions the tissue to be treated
      at the isocenter of a C-arc. This is achieved using AP and 30-degree lateral
      projections, with corresponding horizontal and vertical movements of the patient
      under fluoroscopic guidance. These movements register the anatomic location in
      the coordinate system of the C-arc. In the second step, the therapy head is
      navigated to align the shock wave focus with the isocenter. Position data are
      reported from an optical tracker mounted on the X-ray system, which tracks an
      array of infrared LEDs on the therapy head. The accuracy of the tracking system
      was determined on a test bench, and was calculated to be 1.55 mm (RMS) for an
      angular movement of +/-15 degrees around a calibrated position. Free-hand
      navigation and precise alignment are performed with a single virtual reality
      display. The display is calculated by a computer system in real time, and uses
      graphical symbols to represent the shock wave path and isocenter. In an
      interactive process, the physician observes the display while navigating the
      therapy head towards the isocenter. Precise alignment is achieved by displaying
      an enlarged view of the intersecting graphical symbols. Results from the first
      tests on 100 patients demonstrate the feasibility of this approach in a clinical
      environment.

PMID- 11335957
TI  - Final report of the meeting "modeling & simulation in medicine: towards an
      integrated framework". July 20-21, 2000, National Library of Medicine, National
      Institutes of Health, Bethesda, Maryland, USA.

PMID- 11335958
TI  - Clinical utility of flow cytometry in body fluid cytology: to flow or not to
      flow? That is the question.

PMID- 11335960
TI  - Utility of fine-needle aspiration cytology in the classification of leprosy.
AB  - The role of fine-needle aspiration cytology (FNAC) in the diagnosis of benign
      skin lesions has been restricted primarily to the evaluation of bacteriologic and
      morphologic indices in leprosy. This study was undertaken to evaluate the
      efficacy of FNAC in the diagnosis and classification of lepromatous lesions.
      Aspirates of 94 newly diagnosed cases of leprosy were studied, and the bacterial
      load was determined by modified Ziehl-Neelsen (ZN) stain. A skin biopsy was taken
      from the same site at the same sitting. Frozen and paraffin sections stained with
      hematoxylin-eosin (H&E) and ZN stains were examined from the biopsy specimen. In
      61 of 94 cases (64.9%), the aspirates were satisfactory. Both diagnosis and
      classification of leprosy were possible in 40 of these 61 cases; the rest of the
      aspirates showed nonspecific chronic inflammation. The 39 cases of leprosy where
      a biopsy was available from the same site were classified on FNAC into
      tuberculoid (TT and BT), lepromatous (LL and BL), and midborderline (BB)
      subtypes. Taking the histologic diagnosis and Ridley-Jopling classification to be
      the gold standard, a strong concordance in tuberculoid leprosy cases (18 of 20
      cases, 90%) and in lepromatous cases (15 of 16 cases, 93.7%) was observed.
      Midborderline cases of leprosy posed a problem, and a correct cytohistological
      correlation was observed in only one of the three cases.

PMID- 11335959
TI  - Subgrouping and grading of soft-tissue sarcomas by fine-needle aspiration
      cytology: a histopathologic correlation study.
AB  - To evaluate the accuracy and reproducibility of subgrouping and grading soft
      tissue sarcomas by fine-needle aspiration biopsy (FNAB), a blind review was
      conducted of 84 FNAB specimens from 77 malignant and 7 benign soft-tissue
      lesions. Cytomorphologic subgroups included 31 spindle-cell, 24 pleomorphic, 11
      myxoid, 7 epithelioid/polygonal, 3 small round cell, and 8 nondiagnostic cases.
      Malignancies included one lymphoma and 41 primary, 15 recurrent, and 20
      metastatic soft-tissue sarcomas. Adequacy was defined as a majority of slides
      with at least 5 clusters of 10 unobscured cells. Five originally false-negative
      cases were considered nondiagnostic on review. Sarcoma was recognized in 59 of 64
      adequate cases (92%) with available histology; however, the specific
      histopathologic subtype was identified in only 9 cases (14%). Benign myxoid and
      spindle-cell lesions were difficult to separate from low-grade sarcomas in 4
      cases, and a B-cell lymphoma with sclerosis mimicked a low-grade myxoid sarcoma.
      The assigned cytologic grade accurately reflected the histologic grade in 90% of
      sarcomas when segregated into high and low grades. Pleomorphic, small round cell,
      and epithelioid/polygonal subgroups corresponded to high-grade sarcomas in all
      cases with only minor noncorrelations. Major grading noncorrelations occurred in
      50% of myxoid and 9% of spindle-cell sarcomas. Therefore, attention should be
      given to specimen adequacy, and caution should be exercised when attempting to
      grade myxoid and spindle-cell sarcomas by FNAB.

PMID- 11335961
TI  - Changing clinical course of patients with malignant mesothelioma: implications
      for FNA cytology and utility of immunocytochemical staining.
AB  - The diagnosis of both local recurrences and distant metastases of mesothelioma
      can be accomplished by fine-needle aspiration (FNA) biopsy. Although the previous
      history of mesothelioma provides strong support for recurrent/metastatic
      mesothelioma, other diagnostic possibilities (particularly adenocarcinoma) may
      require exclusion via special stains in some cases. In this study, we report on
      the morphologic findings in 13 cases of mesothelioma which underwent FNA (7
      metastatic lesions, 6 local recurrences). In addition, immunohistochemical
      staining results for 7 cases with available material using antibodies directed
      against cytokeratin AE 1/3 and two antibodies reported to show consistently
      positive results in mesothelioma (calretinin and cytokeratin 5/6) are reported
      and compared to results seen for 10 cases of adenocarcinoma. All cases of
      mesothelioma and adenocarcinoma showed strong staining with cytokeratin AE 1/3.
      Three of 7 cases of mesothelioma showed strong staining with calretinin, while
      only focal staining was detected in 3 additional cases; only one case showed
      positive staining with cytokeratin 5/6. One of 10 cases of adenocarcinoma showed
      calretinin positivity; however, at least focal staining with cytokeratin 5/6 was
      seen in 4 cases. These results suggest that cytokeratin 5/6 is neither a
      sensitive nor specific stain for the diagnosis of mesothelioma in cytology
      material. Calretinin appears to be more specific for mesothelioma but showed
      disappointing sensitivity for this tumor, potentially limiting its diagnostic
      utility in FNA material.

PMID- 11335962
TI  - Detection of loss of heterozygosity at chromosome 3p25-26 in primary and
      metastatic ovarian clear-cell carcinoma: utilization of microdissection and
      polymerase chain reaction in archival tissues.
AB  - Loss of heterozygosity (LOH) at the 3p region is found in up to 50% of epithelial
      ovarian neoplasms. The von Hippel-Lindau (VHL) gene at the 3p25 locus is one of
      the tumor-suppressor genes located at 3p. The role, if any, of the VHL gene locus
      is not clear in ovarian carcinogenesis. We analyzed primary and metastatic
      ovarian clear-cell carcinomas (OCCC) for LOH at 3p25 to determine its frequency
      and its diagnostic utility as an adjunctive tool in the differential diagnosis of
      metastatic clear-cell carcinomas. Microdissection followed by single-step DNA
      extraction and polymerase chain reaction (PCR) amplification, using two
      polymorphic markers flanking the VHL gene locus, was done on archival histology
      and cytology samples from 9 patients with metastatic OCCC. Of the informative
      cases, 43% of the metastatic and 50% of the primary OCCC showed LOH. LOH at the
      VHL gene locus is not uncommon in clear-cell ovarian carcinoma. LOH at 3p25 in
      cytologic specimens may be a valuable adjunct in the diagnosis of OCCC metastasis
      in cytologically equivocal cases. OCCC should enter the differential in clear
      cell carcinomas of unknown primary that show LOH at 3p25. Published 2001 Wiley
      Liss, Inc.

PMID- 11335963
TI  - Fine-needle aspiration cytology of postvaccinial disseminated bacillus Calmette
      Guerin infection.
AB  - Nine patients with primary immunodeficiency who received bacillus Calmette-Guerin
      (BCG) vaccine at birth developed disseminated BCG lesions and presented
      clinically with generalized skin rash and skin nodules. Fine-needle aspiration
      biopsy of the skin nodules and/or enlarged lymph nodes was performed in all
      patients. The most common cytologic pattern encountered was cellular smears
      showing a large number of histiocytes with abundant streaked cytoplasm in a
      background of neutrophils and debris. No granulomas were noted. Ziehl-Neelsen
      (ZN) stain for acid-fast bacilli showed a large number of these bacilli within
      the cytoplasm of the histiocytes, and extracellularly. This pattern was seen in 6
      patients. The cytologic smears from 3 patients showed epithelioid granulomas in a
      background of neutrophils and debris. ZN stain for acid-fast bacilli showed fewer
      numbers of these bacilli compared to the first cytologic pattern. In conclusion,
      the most common cytologic pattern of postvaccinial disseminated BCG lesions in
      immunocompromised patients is a large number of histiocytes with abundant
      streaked cytoplasm in a background of neutrophils and debris. No epithelioid
      granulomas are seen in this pattern. A less frequent pattern is also encountered
      which shows epithelioid granuloma in a neutrophilic background. In both cytologic
      patterns, ZN stain for acid-fast bacilli is positive. However, in the first and
      most common pattern, the number of acid-fast bacilli is much larger than that
      seen in the second pattern. The different cytologic patterns might be related to
      the status of immunity of patients at the time of biopsy.

PMID- 11335965
TI  - Fine-needle aspiration biopsy of a glomus tumor of the stomach.
AB  - A glomus tumor of the stomach was found as an incidental finding on routine
      ultrasound in a 72-yr-old asymptomatic woman. A fine-needle aspiration biopsy
      (FNAB) was performed and was initially interpreted as a well-differentiated
      neuroendocrine neoplasm, possibly a carcinoid tumor. The aspirate revealed
      tightly packed nests or clusters of uniform, small, round to polygonal cells with
      scanty, faintly eosinophilic or clear cytoplasm and ill-defined cell borders. The
      nuclei were uniform, and round to oval, and contained a granular chromatin
      pattern and inconspicuous nucleoli. Very occasional intranuclear cytoplasmic
      inclusions were seen. Laparotomy and a wedge resection of the stomach were
      performed. The surgical pathology findings revealed a glomus tumor which was
      confirmed by immunohistochemical stains and ultrastructural studies. Since glomus
      tumors of the stomach are essentially benign and are amenable to conservative
      excision, it is important to separate them, preoperatively, from more aggressive
      gastric neoplasms. FNAB offers a rapid, cost-effective method of diagnosing this
      entity. We present the cytological, histological, ultrastructural, and
      immunocytochemical features of this particular gastric neoplasm, along with
      differential diagnoses.

PMID- 11335964
TI  - Calcifying aponeurotic fibroma features seen on fine-needle aspiration biopsy:
      case report and brief review of the literature.
AB  - Calcifying aponeurotic fibroma is a rare benign soft tissue proliferation, which
      occurs in the distal extremities in children. We describe a case of calcifying
      aponeurotic fibroma of the hand in a 9 year-old male diagnosed by FNA. Clinically
      and radiographically this mass was felt to be suspicious for sarcoma, likely
      alveolar rhabdomyosarcoma. Cytologic examination revealed benign appearing
      spindled cells, chondroid cells, multinucleated giant cells and calcific debris.
      These features recapitulate the classic histologic features of calcifying
      aponeurotic fibroma. Conservative excision was performed and histologic exam
      confirmed the diagnosis. To the authors' knowledge, this is the first description
      of the cytologic features of this entity.

PMID- 11335966
TI  - Ascitic fluid cytology of adenosarcoma of the ovary: a case report.
AB  - Extrauterine adenosarcoma is very rare and originates in the ovary, adnexa, or
      myometrium. Cytologic study of ascites is very important to determine clinical
      staging of malignant ovarian tumors and provide adequate therapy for recurrence.
      The cytomorphologic features of adenosarcoma have been only rarely described. A
      77-yr-old woman visited a hospital with a complaint of lower abdominal pain for 1
      mo. A tumor originating from the right adnexa in the pelvis, and involving the
      rectum, was found in surgery. In the ascitic fluid cytology, a few dispersed
      tumor cells with large cytoplasm and nuclei were oval-shaped, with nuclear
      invagination. The chromatin was finely granular; one or two nucleoli were
      conspicuous. To our knowledge, this is the fifteenth reported case of
      adenosarcoma of the ovary, and there have been no prior reports describing the
      cytological features of ascitic fluid cells in adenosarcoma of the ovary.

PMID- 11335967
TI  - Fine-needle aspiration cytology and core biopsy of malignant peripheral nerve
      sheath tumor of the uterus: a case report.
AB  - Malignant peripheral nerve sheath tumor (MPNST) is an uncommon mesenchymal
      neoplasm of neural origin. MPNST arising in the uterus is extremely rare. Its
      histologic appearance on this anatomical location has been only rarely reported.
      A 62-yr-old woman with a previous history of partial hysterectomy presented with
      a large pelvic mass in the uterine stump. Fine-needle aspiration (FNA) and core
      biopsy were obtained under ultrasonographic guidance, and the diagnosis of MPNST
      was established. The cytologic and histologic findings were consistent with a
      spindle-cell neoplasm suggestive of MPNST. The tumor cells were focally positive
      for S-100 protein immunostain, thus providing further support for the neoplasm's
      nerve sheath differentiation. The patient had no history of von Recklinghausen's
      disease. Resection of the mass confirmed the diagnosis of MPNST. To our
      knowledge, the FNA cytology of MPNST in this unusual location has not been
      previously reported. FNA cytology, along with core biopsy and immunochemistry, is
      a reliable tool in the diagnosis of MPNST.

PMID- 11335969
TI  - Carcinoma of temporal bone, base of the skull: diagnosis by needle aspiration
      cytology.
AB  - We report on a 68-yr-old male with a destructive bone lesion involving the
      temporal bone at the skull base extending to surrounding osseous structures and
      the infratemporal fossa, defined by needle aspiration cytology as carcinoma in
      association with inflammatory reaction, bacterial type, and bone destruction. The
      technique of the aspiration, which was performed by a cytopathologist directing a
      spinal needle into the region of the destroyed temporal bone as outlined in the
      radiographs of prior magnetic resonance imaging (MRI), is discussed. The
      application of this technique in the cytologic sampling of deeper lesions usually
      of soft or osseous tissues not accessible to ordinary fine-needle aspiration is
      presented. There is also a brief discussion of neoplastic lesions involving the
      temporal bone at the skull base and the anatomic concerns in sampling lesions in
      this difficult-to-approach region of the body.

PMID- 11335968
TI  - Pulmonary parenchymal splenosis.
AB  - We describe the cytologic findings of a case of pulmonary parenchymal splenosis,
      a rare condition that follows lacerating trauma to the spleen, and may masquerade
      as a metastatic neoplasm. Approximately 24 cases of thoracic splenosis have so
      far been reported, the vast majority presenting as pleural-based nodules, and the
      cytological features of only two cases, both belonging to the latter group, have
      been described. We believe our case report to be the first to describe the
      cytological features of an intrapulmonary splenosis, and its features differ from
      the prior cases by having a mixed inflammatory cell infiltrate, with a
      predominance of lymphocytes, plus pulmonary macrophages and occasional
      endothelial cells. This condition has variable cytological features, but the
      correct diagnosis can be made in the presence of appropriate history and
      radiographic findings. Confirmation may require biopsy or radionucleide imaging.

PMID- 11335970
TI  - Fine-needle aspiration diagnosis of medulloblastoma metastatic to the pelvis.
AB  - A 25-yr-old male presented with a cerebellar mass, underwent a suboccipital
      craniotomy, and was diagnosed with medulloblastoma. Six months later he developed
      a large mass in the right iliac crest. Fine-needle aspiration biopsy (FNAB)
      confirmed the diagnosis of metastatic medulloblastoma. The diagnosis of
      metastatic medulloblastoma is usually suspected clinically or radiographically,
      and is uncommonly confirmed by cytologic evaluation. Here we report on a rare
      case of FNAB used to diagnose metastatic medulloblastoma.

PMID- 11335971
TI  - Adenocarcinoma in colonic brushing cytology: High-grade dysplasia as a diagnostic
      pitfall.
AB  - Cytologic evaluation of brushing specimens obtained from the colon may be useful
      in the diagnosis of neoplastic and inflammatory lesions, as previous studies have
      reported favorable sensitivity and specificity figures for this procedure. In
      this study, we report our experience with 80 colonic brushings examined over a 5
      yr period. Thirty cases received an atypical or malignant cytologic diagnosis.
      Nineteen of 20 cases diagnosed cytologically as adenocarcinoma revealed
      adenocarcinoma on biopsy; one case showed only adenomatous epithelium on biopsy
      and subsequent resection. Cases diagnosed cytologically as "atypical" or
      "adenomatous" showed adenocarcinoma, adenoma, and inflammatory conditions upon
      biopsy. Slides from 30 atypical/malignant cases were retrospectively reviewed for
      a number of cytomorphologic features and were correlated with the histologic
      diagnosis. Cases from histologically confirmed adenocarcinoma tended to show
      greater degrees of altered nuclear polarity, nuclear pleomorphism, membrane
      irregularities, and chromatin pattern alterations than those from histologically
      proven adenomatous or inflammatory lesions. The most likely cause of a false
      positive diagnosis in this setting is sampling of an adenoma with high-grade
      dysplasia which fails to meet histologic criteria for adenocarcinoma (invasion of
      the underlying muscularis mucosae). Thus, in the second part of the study, we
      examined histologic sections from surgically excised adenomas to determine the
      frequency with which profound nuclear atypia is at least focally present,
      potentially resulting in a false-positive cytology diagnosis upon brushing.
      Slides from 51 cases were reviewed; cytologic atypia beyond that typically
      observed in adenomas was not observed in 43% of cases. However, profound nuclear
      atypia was present in 6% of cases; cytologic evaluation of a brushing specimen
      from these lesions may have resulted in a false-positive diagnosis of
      adenocarcinoma, despite the histologic diagnosis of adenoma with severe
      dysplasia. The remaining cases demonstrated intermediate degrees of atypia. These
      findings serve to quantitate the frequency with which cytohistologic
      discrepancies might be expected for mass lesions of the colon.

PMID- 11335972
TI  - Cytological findings of adenocarcinomas metastatic to the breast.

PMID- 11335976
TI  - [Rationale for psychophysiological requirements for aircraft display information
      systems].

PMID- 11335975
TI  - [Modern concepts and methodology of means, methods of protection, and safety
      measures for servicemen affected by nonionizing radiation].
AB  - The given information classifies the protection means and methods containing the
      known for today and prospective decisions, as well as process elements of
      development, creation and testing of these means Presented as whole, these
      protection group comprise all the possible aspects of the service-men safety
      problem in operation of military equipment objects, being the source of non
      ionizing radiation.

PMID- 11335977
TI  - [Trends in providing the medical support for safety of high altitude flights].
AB  - The article has analyzed the main development and improvement stages of medical
      support of high-altitude flight safety. Test results of a full-scale model of the
      on-board active flight-safety system [symbol: see text]-2 have been given. There
      have been formulated prospective trends of further studies of the complex system
      development of crew-life support, widespread use of computer-aided technologies,
      as well as practical introduction of rehabilitating hypoxy-based trainings in
      order to increase in the pilot organism functional reserves.

PMID- 11335978
TI  - [Medical support and psychophysiological training of pilots for aircraft with
      high maneuverability].

PMID- 11335979
TI  - [Improvement in carried medical kits].

PMID- 11335980
TI  - [Technical and economic potentialities of magnetic resonance tomography].

PMID- 11335981
TI  - [Establishment and development of domestic aviation ergonomics].

PMID- 11335982
TI  - [Memorial assay about G. P. Rudnev by his student].

PMID- 11335983
TI  - [Directions from head of the General Department of Military Medicine of the
      Ministry of Defence of the Russian Federation].

PMID- 11335985
TI  - Current Perspectives and Future Directions in Medical Statistics. Proceedings of
      a conference. 15-16 April 1999. London, United Kingdom.

PMID- 11335986
TI  - Minimally invasive or conventional valve surgery: operations prevailing in 2020-
      the middle ground.

PMID- 11335984
TI  - Stable non-Robertsonian dicentric chromosomes: four new cases and a review.

PMID- 11335987
TI  - Bibliography.

PMID- 11335989
TI  - 12th International Hypoxia Symposium. March 10-14, 2001. Jasper, Alberta, Canada.
      Abstracts.

PMID- 11335988
TI  - Geneva Biology of Ageing Workshop 2000: phagocytes, inflammation, and ageing.

PMID- 11335990
TI  - Selected papers from the 3rd International Conference on Bipolar Disorder.
      Pittsburgh, Pennsylvania, USA. June 1999.

PMID- 11335992
TI  - The biotechnology industry's Frankensteinian creation.

PMID- 11335993
TI  - Experiments in the rat pentylenetetrazole infusion threshold model of the
      ketogenic diet.

PMID- 11335994
TI  - [Music as symbol of freedom: 100th anniversary of Giuseppe Verdi].

PMID- 11335995
TI  - [Legal aspects of endoscopy].

PMID- 11335996
TI  - [Internist--primary care].

PMID- 11335997
TI  - [Introduction to the story of the Psychosomatic Department at the Medical Clinics
      of the Ludwig-Maximilians University, Munich].

PMID- 11335998
TI  - [Prevention of osteoporotic vertebral fractures].

PMID- 11335999
TI  - [Hygiene for flexible endoscopy].

PMID- 11336000
TI  - [Evidence-based medicine in clinical practice, more economics in patient care?
      Presented at the 21st Forum Niedersachsen, September 25th, 1999].

PMID- 11336001
TI  - Asthma from diisocyanates is not mediated through a Type IV, patch-test-positive
      mechanism.
AB  - The mechanism of occupational asthma from diisocyanates (DI)(1-10)(Fig. 1) is not
      fully known; only about 10%-30% of such patients have specific IgE antibodies to
      DI (3, 11, 12). A T-cell mediated response has been considered to be involved in
      DI asthma (13) and we therefore wondered whether patch testing might be of any
      help in its diagnosis.

PMID- 11336003
TI  - Role of methylchloroisothiazolinone/methylisothiazolinone (Kathon CG) in
      poikiloderma of Civatte.

PMID- 11336002
TI  - "Lucky Luke" contact dermatitis from diapers: a new allergen?
AB  - "Lucky Luke" contact dermatitis is a particular pattern of diaper dermatitis,
      reminiscent of a cowboy's gunbelt holsters (1).

PMID- 11336004
TI  - Allergic contact cheilitis due to shellac.

PMID- 11336005
TI  - Consort contact urticaria due to amoxycillin.

PMID- 11336006
TI  - Compositae mix: what is the optimum concentration for patch testing?

PMID- 11336007
TI  - Oral symptoms due to zinc as a minor component of dental amalgam.

PMID- 11336008
TI  - Keyboard wrist pad.

PMID- 11336009
TI  - Fixed drug eruption from quinolones with a positive lesional patch test to
      ciprofloxacin.

PMID- 11336010
TI  - Contact dermatitis from Solvent Yellow 146 in a permanent marker.

PMID- 11336011
TI  - Sensitivity to adipic acid used in polyester synthesis.

PMID- 11336012
TI  - Allergic contact dermatitis caused by palladium on titanium spectacle frames.

PMID- 11336013
TI  - Report from the register of occupational skin diseases in northern Bavaria (BKH
      N).

PMID- 11336014
TI  - The usefulness of patch testing on the previously most severely affected site in
      a cutaneous adverse drug reaction to tetrazepam.

PMID- 11336015
TI  - Systemic contact dermatitis from cinchocaine.

PMID- 11336016
TI  - The dental face mask--the most common cause of work-related face dermatitis in
      dental nurses.

PMID- 11336017
TI  - Protein contact dermatitis in a fisherman using maggots of a flesh fly as bait.

PMID- 11336018
TI  - Seat-belt dermatitis from Disperse Blue dyes.

PMID- 11336019
TI  - [Colorectal Cancer. Proceedings of the IV National Conference of the Italian
      Association of Medical Oncology. Bologna, 4-6 March 2001].

PMID- 11336020
TI  - Multidrug-resistant Streptococcus pneumoniae.

PMID- 11336021
TI  - Multidrug-resistant Streptococcus pneumoniae.

PMID- 11336022
TI  - Multidrug-resistant Streptococcus pneumoniae.

PMID- 11336023
TI  - Cellular telephones and brain tumors.

PMID- 11336024
TI  - Cellular telephones and brain tumors.

PMID- 11336025
TI  - Cellular telephones and brain tumors.

PMID- 11336026
TI  - Allergy and IgE antibodies.

PMID- 11336027
TI  - Coexistence of hypertrophic cardiomyopathy and fibromuscular dysplasia of the
      superior mesenteric artery.

PMID- 11336028
TI  - Beginning to do research. Tips for literature search and reference collection.

PMID- 11336029
TI  - Grading system for inflammation in ulcerative colitis.

PMID- 11336030
TI  - Insulin and gall stones.

PMID- 11336031
TI  - Heparin as an anti-inflammatory agent: it's no GAG to forget about chemokines.

PMID- 11336032
TI  - Management of variceal haemorrhage in cirrhotic patients.

PMID- 11336033
TI  - Long term follow up of interferon responder children with chronic hepatitis B.

PMID- 11336034
TI  - Renal sodium handling in preascitic cirrhosis.

PMID- 11336035
TI  - Posterior alexia after right occipitotemporal infarction.

PMID- 11336036
TI  - De novo partial duplication of 17p associated with Charcot-Marie-Tooth disease
      type 1A.

PMID- 11336037
TI  - Bilateral vestibular failure as a unique presenting sign in carcinomatous
      meningitis: case report.

PMID- 11336038
TI  - Loss of silent reading in frontotemporal dementia: unmasking the inner speech.

PMID- 11336039
TI  - Anti-Jo-1 positive inclusion body myositis with a marked and sustained clinical
      improvement after oral prednisone.

PMID- 11336040
TI  - Upholsterer's PIN.

PMID- 11336041
TI  - Neurocysticercosis and epilepsy in developing countries.

PMID- 11336042
TI  - High psychiatric morbidity in patients with medically unexplained symptoms.

PMID- 11336043
TI  - The psychoses of epilepsy.

PMID- 11336044
TI  - Diagnostic criteria of multiple system atrophy.

PMID- 11336045
TI  - From the Centers for Disease Control and Prevention. Tuberculosis treatment
      interruptions--Ivanovo Oblast, Russian Federation, 1999.

PMID- 11336046
TI  - From the Centers for Disease Control and Prevention. Evaluation of a directly
      observed therapy short-course strategy for treating tuberculosis--Orel Oblast,
      Russian Federation, 1999-2000.

PMID- 11336047
TI  - From the Centers for Disease Control and Prevention. Update: Assessment of risk
      for meningococcal disease associated with the Hajj 2001.

PMID- 11336048
TI  - JAMA patient page. Alcohol use and heart disease.

PMID- 11336049
TI  - Epidermodysplasia verruciformis defines a subset of cutaneous human
      papillomaviruses.

PMID- 11336050
TI  - How I remove a spontaneous cerebellar hematoma in a deteriorating patient.

PMID- 11336051
TI  - Being positive about the smear.

PMID- 11336052
TI  - Churg-Strauss syndrome with montelukast.

PMID- 11336053
TI  - Malignant mesothelioma.

PMID- 11336054
TI  - Assisted discharge for patients with exacerbations of COPD.

PMID- 11336055
TI  - Racial differences in the response to drugs--pointers to genetic differences.

PMID- 11336056
TI  - Upper gastrointestinal toxicity of rofecoxib and naproxen.

PMID- 11336057
TI  - Upper gastrointestinal toxicity of rofecoxib and naproxen.

PMID- 11336058
TI  - Nasal carriage of Staphylococcus aureus.

PMID- 11336059
TI  - Nasal carriage of Staphylococcus aureus.

PMID- 11336060
TI  - Nasal carriage of Staphylococcus aureus.

PMID- 11336061
TI  - Nasal carriage of Staphylococcus aureus.

PMID- 11336062
TI  - Diastolic dysfunction and hypertension.

PMID- 11336063
TI  - Diastolic dysfunction and hypertension.

PMID- 11336064
TI  - Diastolic dysfunction and hypertension.

PMID- 11336065
TI  - Long-term outcomes after treatment for refractory immune thrombocytopenic
      purpura.

PMID- 11336066
TI  - [The effects of Vitreoscilla hemoglobin expression on growth and antibiotic
      production in Streptomyces cinnamonensis].
AB  - Streptomyces cinnamonensis A-10 is a monensin ? producing strain. pHZ1252 is an
      E. coli-Streptomyces shuttle vector for expressing VHb, in which vhb structural
      gene is controlled by thiostrepton-inducible promoter PtipA. pHZ1252 was unstable
      in S. cinnamonensis, occurring deletion recombination. The deletion DNA fragment
      of pHZ1252 included not only part of E. coli plasmid but also vhb gene. However,
      plasmid pHZ1252 isolated from S. avermitilis transformants, which lost part of E.
      coli plasmid but still contained vhb gene and PtipA was stable in S.
      cinnamonensis and expressed VHb with biological activity after thiostrepton
      induction. Shake flask fermentation experiments showed that the presence of VHb
      in S. cinnamonensis efficiently enhanced cell growth and improved antibiotic
      production under aeration-poor conditions.

PMID- 11336067
TI  - The somatic components of disease. 1956.

PMID- 11336068
TI  - Functional technic in osteopathic manipulative treatment. 1956.

PMID- 11336069
TI  - Lucio's phenomenon: clinical and therapeutic aspects.
AB  - We report four cases of necrotizing reactions of the Lucio's phenomenon type, an
      entity rarely observed in Brazil despite the high prevalence of leprosy.
      Clinical, histopathological and therapeutic aspects are described and compared to
      those reported in the literature for cases classified as diffuse, non-nodular
      lepromatous leprosy with Lucio's phenomenon.

PMID- 11336070
TI  - Vertical induction of the inclusion body hepatitis/hydropericardium syndrome with
      fowl adenovirus and chicken anemia virus.
AB  - The hypothesis that fowl adenovirus (FAV) and chicken anemia virus (CAV),
      transmitted vertically and simultaneously, induce the inclusion body hepatitis
      (IBH)/hydropericardium (HP) syndrome in progeny chickens was tested. Thus, 35-wk
      old light brown layer breeders, showing absence of antibodies against FAV and
      variable titers against CAV, were intramuscularly singly infected with the FAV
      serotype 4 isolate 341 or dually infected with CAV (isolate 10343) and FAV. All
      hens (groups A [FAV alone], B [FAV + CAV], and C [noninfected]) were clinically
      healthy throughout the experimental period. Both infectious viruses FAV and CAV
      were isolated from progenies obtained as early as 5 days after infection of their
      breeders. Hematocrit, serum proteins, and aspartate-aminotransferase values
      showed a few statistical differences between the progeny groups. Most of these
      differences were detected in the progeny chickens of group B. However, almost all
      values met reference values for the species. The pathologic findings showed that
      progeny chickens obtained from both singly and dually infected breeders developed
      macroscopic and histopathologic changes of IBH/HP. The pathologic findings shown
      by progeny chickens of group A (FAV) were not expected because neither synergism
      nor prior immunodepression by CAV was concurrent. Chickens of group B (CAV + FAV)
      also developed IBH/HP. Although not many differences in the evaluated parameters
      between groups A and B were statistically significant, most pathologic findings
      of group B indicated a more severe manifestation of the disease. However, because
      FAV alone did reproduce the syndrome, the results shown by group B would not
      allow a definitive confirmation of the hypothesis that the association of FAV and
      CAV is necessary for the successful induction of the IBH/HP syndrome in chickens
      when transmitted vertically.

PMID- 11336071
TI  - Multicenter study of the efficacy and safety of fexofenadine 60 mg. twice daily
      in 108 Thai patients with chronic idiopathic urticaria.
AB  - Fexofenadine is a non-sedating antihistamine indicated for relieving symptoms
      from allergic conditions with a rapid onset of action without cardiotoxic risks.
      Controlled studies showed that fexofenadine 180 mg daily provides significant
      relief of symptoms of chronic idiopathic urticaria (CIU). The purpose of this
      study was to demonstrate the efficacy and safety of fexofenadine 60 mg twice
      daily in Thai patients with CIU in a multicenter trial. Patients were assigned to
      receive twice daily doses of fexofenadine 60 mg for 6 weeks. Patients rated
      symptom severity every night, investigators rated patients' signs and symptoms at
      recruitment and at 1, 3 and 6 weeks. Ninety eight out of 108 patient (90.7%)
      completed the study. The patients reported 95 per cent improvement and, of those,
      91 per cent had very favorable responses (excellent 15%, very good 42%, good 30%,
      fair 8%). The objective assessment by their physicians paralleled those
      responses. Fexofenadine provided a rapid clinical response that was significantly
      superior to before treatment in relieving symptoms of CIU (p < 0.001). Adverse
      events occurred in 20 cases (18.5%), mostly mild headache and drowsiness.
      Fexofenadine 60 mg twice daily provides effective relief of the symptoms of CIU
      with minimal adverse events.

PMID- 11336072
TI  - Nosocomial bloodstream infection in pediatric patients: Siriraj Hospital,
      Bangkok; 1996-1999.
AB  - A retrospective study on nosocomial bloodstream infection (NBSI) in pediatric
      patients hospitalized at Siriraj Hospital from January 1996 to December 1999 was
      performed. Of the 18,087 blood specimens sent for culture, 533 (3%) were positive
      for organisms after 72 hours of hospitalization and were defined as NBSI. The
      rate of NBSI detected in blood culture specimens was highest among neonates
      (5.2%). Gram-positive cocci and gram-negative rods caused NBSI in an equal
      proportion (46% and 44% respectively) and Candida caused 10 per cent of NBSI.
      Coagulase-negative staphylococci was the most common pathogen followed by K.
      pneumoniae and Enterobacter. Antibiogram showed that 15 of the 35 (43%) S. aureus
      identified were methicillin-resistant. Only 35-38 per cent of Enterobacteriaceae
      were sensitive to cefotaxime or ceftazidime. Cefoxitin was still effective
      against 95 per cent of K. pneumoniae. Compared with other third generation
      cephalosporins, combination of cefoperazone and betalactamase-inhibitor
      (sulbactam) possessed an increased in vitro efficacy against K. pneumoniae,
      Enterobacter, E. coli, Acinetobacter and non-fermentative gram-negative rods.
      Resistant rate of amikacin among all gram negative rods was 25-69 per cent.
      Ciprofloxacin sensitivity varied from 62-100 per cent among all gram-negative
      rods. Imipenem was excellent against all gram-negative rods with the sensitivity
      of 80-100 per cent. Epidemiological data of this study is important for the
      decision of the appropriate empirical antimicrobial treatment in our hospital.

PMID- 11336073
TI  - Reproductive outcome following hysteroscopic treatment of the septate uterus: a
      result of 28 cases at Ramathibodi Hospital.
AB  - We reported the reproductive outcome of 28 patients with septate uterus who
      underwent hysteroscopic metroplasty between August 1994 and October 1999 at
      Ramathibodi Hospital. The majority of septa were partial. Most of the patients
      had recurrent pregnancy losses. Division of the septum was performed with
      scissors in 7, a new device of Versapoint bipolar electrode in 10, and by means
      of resectoscope in 11 patients. The operating time varied from 45 to 70 minutes
      with an average time of 50+/-5.5 minutes which included the time for laparoscopy.
      The blood loss during the operation was minimal. All 28 patients were discharged
      a few hours after the operation. There were no serious complications attributed
      to this study. Most of the patients had minor spotting but no significant
      bleeding for a few days after hysteroscopic surgery. Of the 28 patients, 4
      patients have not tried to conceive because of personal reasons, and the other 5
      patients were lost to follow-up. Fifteen patients who had postoperative
      hysterosalpingograms, demonstrated a normal uterine cavity. There were a total of
      20 pregnancies after a mean period of 24+/-1.4 (range 6-42) months following
      hysteroscopic treatment, of which 15(75.0%) were carried to term, 3(15.0%) were
      spontaneous abortions, and 2(10.0%) are in progress. The rate of pregnancy
      wastage in the post-treatment group was 15 per cent compared with 96.3 per cent
      in the pretreatment group.

PMID- 11336074
TI  - Botulinum toxin treatment of the sixth nerve palsy: an experience of 5-year
      duration in Thailand.
AB  - Forty-five patients (48 eyes) with sixth nerve palsy were treated with botulinum
      toxin injection to antagonist medial rectus muscle at Siriraj Hospital from
      October 1995 to September 2000. The common causes of palsy were ischemia, trauma
      and inflammation. Thirty-eight patients (group I) had an interval to treatment of
      less than 24 weeks (average, 8.7 weeks) and seven patients (group II), longer
      than 24 weeks. The mean pre-injection esodeviation and extent of abduction in
      group I were 28.1 prism diopters (PD) and 28.4 per cent, and in group II were 38
      PD and 8.1 per cent respectively. After a mean follow-up of 12.2 months, twenty
      seven (71.1%) patients in group I recovered completely after the first injection
      and three (7.9%), after the second injection with a mean interval to recovery of
      8.1 weeks. One (14.3%) of 7 patients of group II obtained complete recovery
      without fusion. Twenty-six (83.9%) of 31 patients with complete resolution
      achieved binocular function. We conclude that botulinum toxin treatment is a safe
      and effective alternative to traditional surgery of acute onset sixth nerve
      palsy.

PMID- 11336075
TI  - Accuracy of hysteroscopic diagnosis of endometrial polyps.
AB  - OBJECTIVE: To evaluate the diagnostic accuracy of endometrial polyps by
      hysteroscopy. MATERIAL AND METHOD: One hundred and sixty five women undergoing
      diagnostic hysteroscopy between January 1996 and December 1998 at the Gynecologic
      Endoscopy Unit, King Chulalongkorn Memorial Hospital were recruited in this
      study. The hysteroscopic diagnosis was compared with the histopathology by
      endometrial curettages performed after hysteroscopy. RESULTS: Endometrial polyps
      were diagnosed by hysteroscopy in 54 patients (32.73%). When compared to tissue
      pathology, we found an accuracy of 81.21 per cent, sensitivity of 92.59 per cent,
      specificity of 78.98 per cent, positive predictive value of 46.29 per cent,
      negative predictive value of 98.19 per cent, false positive of 17.57 per cent and
      false negative of 1.21 per cent. CONCLUSION: For endometrial polyps, diagnostic
      hysteroscopy yields a high accuracy but low positive predictive value. Therefore,
      endometrial biopsy is necessary to confirm diagnosis of endometrial polyps by
      hysteroscopy.

PMID- 11336076
TI  - Experience of ApoE study in Thai elderly.
AB  - The association between ApoE E4 and dementia is reported in Alzheimer's disease
      and other dementia such as in multi-infarct dementia. OBJECTIVES: To examine the
      association between apolipoprotein E genotype (ApoE) and dementia in Thai elderly
      and patients to examine the alleles frequencies of ApoE in a Thai population.
      MATERIAL AND METHOD: Seventy-eight cases and ninety-four controls from a
      community based population were recruited. Their ages were all over 50 years.
      Dementia was diagnosed by DSM IV criteria. Blood was taken and stored for DNA
      extraction and for restriction enzyme analysis of ApoE genotype. Descriptive
      analysis and odds ratios from SPSS 9.0 program were used in this study. RESULTS:
      Alleles frequencies of ApoE E2, E, E4 in normal controls were 0.03, 0.80, 0.17
      and alleles frequencies of ApoE E3, E4 in dementia subjects were 0.71 and 0.29,
      respectively. Odds ratios for dementia risk of apolipoprotein genes were as
      follows: 0.62 for ApoE E3 and 1.98 for ApoE E4. In this study, forty-two dementia
      subjects had Alzheimer's disease. Fifty nine point five per cent of Alzheimer's
      disease subjects carried ApoE E4 (positive predictive value is 0.60). CONCLUSION:
      Thai elderly carry ApoE genotype distribution similar to that reported in other
      ethnic groups. Bearing ApoE E4 gene increases the risk of developing dementia.
      The use of ApoE genotyping can only be a diagnostic adjunct for Alzheimer's
      disease.

PMID- 11336077
TI  - Adrenocortical tumors in children.
AB  - Adrenocortical tumors are very rare in children. The records of seven patients
      (four boys and three girls) who attended Srinagarind Hospital between January
      1986 and September 2000 were retrospectively reviewed. Virilization and
      hypertension were found in four patients, two of whom had untreated congenital
      adrenal hyperplasia. Hypertension or virilization was the single manifestation
      found in two other patients. Only one patient showed clinical symptoms of
      Cushing's syndrome and another nonfunctioning tumor in Down's syndrome. Abdominal
      ultrasonography was helpful in locating the tumors. Unilateral tumors were found
      in all of the patients and surgical exploration was done in six of them.
      Pathological examination revealed four adrenocortical carcinomas, one adrenal
      gland hyperplasia and one lipoma. The two patients in which the cancer
      metastasized to the liver and lungs died 1 and 1 1/2 months after diagnosis,
      respectively. The authors concluded that virilization and hypertension remain the
      primary diagnostic symptoms of adrenocortical tumors in children. Early detection
      and adrenalectomies prolonged the survival time in these patients.

PMID- 11336078
TI  - Randomized double blind, placebo-controlled study of pilocarpine administered
      during head and neck irradiation to reduce xerostomia.
AB  - PURPOSE: Pilocarpine hydrochloride administered during head and neck irradiation
      was evaluated for its ability to relieve xerostomia and its adverse effects.
      MATERIAL AND METHOD: A total of 60 head and neck cancer patients were enrolled in
      a randomized, double blind, placebo-controlled trial. Each patient had both
      parotid glands treated with a radiation dose of at least 50 Gy. Patients received
      jelly containing pilocarpine or placebo 5.0 mg (1 cc.) tid at meal times during
      radiation. Pilocarpine was administered beginning on the first day of radiation
      and continued until radiation was completed. Patients were evaluated for
      symptomatic relief by responding to questionnaires using a Visual Analogue Scale
      (VAS). Questionnaires measured relief of oral dryness, oral discomfort,
      difficulty in chewing and swallowing, speaking, and sleeping. Evaluation was
      conducted preradiation as a baseline, weekly during radiation and monthly until 6
      months after radiation was completed. RESULTS: The baseline characteristics,
      disease and radiation technique including field arrangement and total dose, were
      not significantly different between the two groups. There was no statistically
      significant subjective difference in xerostomia, including oral dryness, oral
      discomfort, inability to chew and swallow, speak and sleep, during and
      postradiation between the two groups. The adverse effects were non-specific
      symptoms such as nausea, vomitting, dizziness, urinary frequency, palpitation,
      sweating and tearing. The adverse effects during radiation and postradiation were
      not significantly different between the two groups. CONCLUSION: It was concluded
      that pilocarpine hydrochloride administered during head and neck irradiation
      produced subjectively insignificant benefit in relieving xerostomia with
      acceptable side effects.

PMID- 11336079
TI  - The risks of lymph node metastasis and the prognostic factors in carcinoma of the
      penis: analysis of 50 patients treated with bilateral ilioinguinal
      lymphadenectomy.
AB  - OBJECTIVE: To determine the risks of inguinal and pelvic lymph node metastasis as
      well as the prognostic factors in carcinoma of the penis. METHOD: Fifty patients
      with squamous cell carcinoma of the penis who consecutively underwent immediate
      bilateral ilioinguinal lymphadenectomy after treatment of the primary tumor.
      Clinical features were evaluated to determine the risk of inguinal and pelvic
      lymph node metastasis as well as prognostic factors. RESULTS: Patients with
      palpable inguinal lymph node had a high risk of inguinal lymph node metastasis
      compared with patients with a non palpable inguinal lymph node (p = 0.002).
      Patients with poor differentiated tumors had a high risk of pelvic lymph node
      metastasis compared with patients with well or moderately differentiated tumors
      (p = 0.021). Prognostic factors significantly related to survival were the
      clinical status of the inguinal lymph node, histological grade and the status of
      lymph node metastasis (N stage). None of the patients with stage N0 and N1 died
      with the longest follow-up at 85 and 67 months, respectively. Cumulative
      survivals were 0.6 at follow-up at 36 months for the patients with stage N2 and
      0.5 at follow-up at 18 months for patients with stage N3. CONCLUSION: The
      clinical status of inguinal lymph node was related to the risk of inguinal lymph
      node metastasis. Histological grade was related to the risk of pelvic lymph node
      metastasis. The clinical status of the inguinal lymph node, histological grade
      and pathological N stage were the important factors affecting the prognosis.

PMID- 11336080
TI  - The observation of immunosuppressor(s) derived from cultured tumor cells and its
      partial neutralization with OK-432.
AB  - Malignant tumors such as brain tumors have been reported to be associated with
      immunosuppression caused by certain tumor-secreted cytokines. The reversion of
      tumor-derived immunosuppression has not been described. The use of OK-432, an
      immunomodulatory agent prepared from Su-strain of Streptococcus pyogenes A3, to
      activate peripheral blood mononuclear cells from a patient with glioblastoma
      multiforme has demonstrated a sharp rise in proliferative response. This
      proliferative response was compromised in the presence of living and irradiated
      autogeneic cancer cells. The conditioned media from cultured cells of
      glioblastoma multiforme, astrocytoma, and cholangiocarcinoma were tested for
      immunosuppressive ability. We found that conditioned media from 3 of 4 cases of
      glioblastoma, all 3 cases of astrocytoma, and 1 case of cholangiocarcinoma
      exhibited immunosuppressive activity toward the proliferative response of
      allogeneic peripheral blood mononuclear cells to phytohemagglutinin. This is the
      first report that cholangiocarcinoma produces soluble immunosuppressor(s). Our
      finding suggested that soluble substance(s) as well as direct cell-cell contact
      between tumor cells and mononuclear cells play roles in the observed tumor
      derived immunosuppression.

PMID- 11336081
TI  - Evaluation of forearm bone mineral density: comparison of dominant and non
      dominant forearms.
AB  - For evaluation of forearm bone mineral density (BMD), (1) BMD of corresponding
      sites of dominant and non-dominant forearms were compared and (2) characteristics
      of each of the 4 regions of interest (ROIs) including supradistal, distal 1/10,
      distal 1/6 and distal 1/3 along the long bone of both forearms were analyzed. One
      hundred and forty one women (79 normal and 62 osteoporotic) were recruited by
      randomized selection from the department of Nuclear Medicine of Phramongkutklao
      Hospital. Both dominant and non-dominant forearms of each subject were scanned by
      Panasonic (DXA-70) dual energy X-ray absorptiometry (DEXA) on the same day.
      Lumbar spine BMD was also measured by Hologic DEXA (QDR-4500) and WHO criteria
      for diagnosis of osteoporosis was applied for identifying osteoporosis and normal
      groups. The results showed that none of the corresponding sites of BMD of both
      forearms were significantly different (p>0.05 for all). The BMD from distal to
      proximal of each long bone (radius and ulna) of both forearms was gradually
      increased in osteoporosis and normal groups. Further distal sites of the forearms
      and lower BMD were found. Comparison between mean BMD at corresponding sites in
      normal and osteoporotic groups, had significantly different BMD at both radii for
      all ROIs (p<0.05). While BMD at corresponding sites of both ulna in the 2 groups
      was not significantly different (p>0.05). A great percentage change of mean BMD
      in the osteoporotic group was seen at supradistal and distal 1/10 of both
      forearms when using BMD in the normal group as control. We suggest that both
      distal radii especially at supradistal and distal 1/10 sites should be scanned in
      routine practice. The distal location of the forearms had a relatively smaller
      amount of surrounding soft tissue than the proximal.

PMID- 11336082
TI  - The Amatsu tracheoesophageal shunt operation for voice restoration after total
      laryngectomy.
AB  - Vocal rehabilitation after total laryngectomy using tracheoesophageal shunt with
      sphincter mechanism or Amatsu's operation was performed in 12 patients at the
      department of Otolaryngology, Chiang Mai University from January 1993 to December
      1998. Serviceable voice was attained within 10-14 days postoperatively. The
      success rate of voice restoration was 75 per cent with a good maximum phonatory
      time of 8 seconds. Tracheal aspiration which was found in 4 patients was managed
      conservatively without complication. The Amatsu tracheoesophageal shunt is a
      single stage operation which provides the patients with a good success rate of
      voice restoration, few complications, easy learning, and prosthesis free.

PMID- 11336083
TI  - Effects on urinary albumin excretion and renal function changes by delapril and
      manidipine in normotensive type 2 diabetic patients with microalbuminuria.
AB  - This study was designed to investigate the effect of delapril, an ACE inhibitor,
      and manidipine, a long action calcium antagonist, on persistent microalbuminuria
      in normotensive type 2 diabetic patients. Sixty type 2 diabetic patients were
      randomized to take delapril 30 mg/day or manidipine 10 mg/day for 48 weeks, in an
      open label design. Twenty eight of thirty subjects in the delapril group and
      twenty nine of thirty in the manidipine group completed the study. Urine albumin
      excretion as measured by the urinary albumin creatinine ratio decreased
      significantly in both groups (112.0+/-60.9 to 95.3+/-64.9 mg/g and 108.5+/-51.0
      to 96.4+/-53.5 mg/g in the delapril and manidipine group respectively, p < 0.05,
      by paired t-test). Systolic and diastolic blood pressure were not significantly
      changed after treatment in the delapril group but significantly decreased in the
      manidipine group (130.9+/-7.1/80.2+/-6.1 to 127.2+/-7.1/78.0+/-5.3 mm/Hg, p <
      0.05, by student's paired t-test). After 48 weeks of treatment, two patients in
      the delapril group and one patient in the manidipine group converted to
      normoalbuminuria (urinary albumin:creatinine ratio < 30 mg/g) and one patient in
      each group progressed to overt nephropathy (urinary albumin:creatinine ratio >
      300 mg/g). There were no significant changes in fasting plasma glucose, HbA1c,
      serum fructosamine, creatinine, potassium and lipid profiles after 48 weeks of
      treatment in both groups. Two cases in the delapril group were withdrawn during
      the study because of an intolerable cough and one case in the manidipine group
      because of intolerable dizziness and headache. In conclusion, both delapril and
      manidipine are effective in the reduction of microalbuminuria in normotensive
      type 2 diabetic patients with persistent microalbuminuria.

PMID- 11336084
TI  - False-negative meniscal tear in MR imaging using non fat-suppressed techniques.
AB  - Magnetic resonance (MR) imaging of menisci has a diagnostic accuracy of more than
      90 per cent when the images are properly obtained. Errors in the interpretation
      of MR images may be related to many problems, resulting in false positive or
      false negative readings. We conducted this study to evaluate the prevalence of
      false negative results, using arthroscopy as gold standard. Matched MR imaging
      (performed before July 1997) and arthroscopic findings of the menisci in 63
      consecutive patients were retrospectively reviewed separately by imaging planes
      and sequences used, by the site of tear, and by the site of meniscus (medial or
      lateral meniscus). The number and percentage of false-negative results were
      recorded. We found that with non fat-suppressed MR techniques, missed tear (false
      negative reading) of both menisci occurred predominantly in the meniscal body.
      The prevalence depends on imaging plane and sequence used. Among the techniques
      reviewed, sagittal T2-weighted (T2W) sequence had the highest prevalence of
      undetected meniscal tear.

PMID- 11336085
TI  - The pregnancy rates--a retrospective comparison of tubal and uterine embryo
      transfers.
AB  - Tubal embryo transfer (TET), which involves an embryo transfer via the uterine
      tube, has a possible advantage over uterine embryo transfer (UET) due to more
      natural timing of embryo exposure to the uterine cavity. This study was carried
      out to evaluate the pregnancy rate of TET versus UET. Eight hundred and ninety
      seven consecutive patients who underwent embryo transfers from July 1997 to June
      1999 in Bielefelder Institut fuer Fortpflanzungsmedizin (BIF.), Germany were
      included in this study. Two hundred and eighty-six pregnancies were achieved in
      167 cases (31.4%) after TET and 119 cases (24.6%) after UET. The abortion rate of
      the TET group was 12.0 per cent while that of the UET group was 23.3 per cent.
      Our results showed that TET has a significantly increased clinical pregnancy rate
      and significantly decreased abortion rate. There is an advantage in transferring
      embryos to the fallopian tube in infertile couples with male factor infertility
      and unexplained infertility. We recommend TET as the first choice for embryo
      transfer in infertile couples with patent fallopian tubes and with no evidence of
      pelvic adhesion and/or endometriosis.

PMID- 11336086
TI  - Occupational lumbar disc herniation among Thai workers claimed for compensation.
AB  - The study was conducted at the Medical Committee Office to the Compensation Fund,
      from March to August 2000, the documents and medical records of 37 claimants of
      Thai workers who were diagnosed with occupational lumbar disc herniation were
      analyzed, 78.4 per cent were male. The most common age was between 26-35 years.
      About half of the workers had a monthly salary of less than 6,150 baht and had
      worked for less than 5 years. The most common risk factor was lifting, which
      accounted for 64.9 per cent and the chance of severity was twice that of other
      types of work. Ergonomic intervention should be properly implemented.

PMID- 11336087
TI  - Reversibility of tachycardiomyopathy after successful radiofrequency catheter
      ablation: intermediate results.
AB  - Left ventricular function in patients with tachycardia induced cardiomypopathy
      can improve after cessation of the arrhythmia. We reported the intermediate
      results of 10 patients, 6 men and 4 women, with tachycardiomyopathy who
      successfully underwent radiofrequency catheter ablation (RFCA) for incessant
      tachycardia. Three had right atrial tachycardia, 5 ventricular tachycardia (2 and
      3 from the right and left ventricles, respectively), 1 atrial flutter and 1 right
      accessory pathway. During the mean follow-up period of 19 months (range 11-38
      months), one patient, right atrial tachycardia, had recurrence and reablation was
      successfully done without recurrence. Left ventricular ejection fraction,
      endsystolic and diastolic diameters from echocardiography gradually improved from
      35 per cent, 51 and 61 mm to 58 per cent, 36 and 52 mm, respectively (p<0.001).
      The mean duration of reversibility was 7 months (range 1-15 months). There was no
      recurrence of tachycardiomyopathy after the return of left ventricular function.
      Conclusion, RFCA can terminate tachyarrhythmia and lead to significant
      improvement of left ventricular diameters and systolic function in patients with
      tachycardia induced cardiomyopathy.

PMID- 11336088
TI  - Sacrococcygeal teratoma: 25 year experience.
AB  - We retrospectively studied all thirty-five children (M 6, F 29) with
      sacrococcygeal teratomas admitted to Siriraj Hospital between 1974 and 1999.
      Although an abdominal delivery is recommended for lesions greater than 5 cm to
      avoid dystocia, the average diameter of masses which required interventions from
      dystocia (n = 3) was not different from vaginal delivery (n = 27). All except two
      first presented with sacral masses recognized at birth. One patient presented
      with an abdominal mass and the last one was diagnosed after suffering from
      difficulty in urination. Ninety-seven per cent of cases were completely excised
      initially (32 sacral, 2 abdomino-sacral approaches), however, six patients
      required other treatment for recurrent diseases. One mature teratoma recurrence
      was resected. Two patients who had malignant recurrences following complete
      benign excisions, died from advanced malignancy. Four presented with malignancy
      initially. Wound infection, bladder atony and UTI were the most common
      complications postoperatively. Advanced malignancy was the major cause of death.
      No patient died directly from the procedure.

PMID- 11336089
TI  - Prenatal sonographic markers of trisomy 21.
AB  - OBJECTIVE: To describe the sonographic characteristics of fetuses with trisomy
      21. DESIGN: A prospective descriptive analysis. SETTING: Department of Obstetrics
      and Gynecology, Faculty of Medicine, Maharaj Nakorn Chiang Mai Hospital, Chiang
      Mai University. SUBJECTS: Pregnancies at risk of trisomy 21 between 14-27 weeks'
      gestation. RESULTS: Thirty-six fetuses with subsequently proven trisomy 21 were
      prenatally evaluated by ultrasound in the second trimester. The main indications
      for detailed ultrasound examinations were advanced maternal age and abnormal
      findings on routine ultrasound. All of them had chromosome analysis by
      amniocentesis or cordocentesis. Nineteen (52.78%) had one or more abnormal
      findings. The common sonographic findings included thickened nuchal fold
      (33.33%), short femur (19.44%), and mild pyelectasis (22.22%). The other uncommon
      abnormalities included major anomalies (cardiac malformations, ventriculomegaly,
      duodenal atresia, esophageal atresia), hyperechoic bowel, echogenic intracardiac
      foci, abnormalities of extremities. In this study, rare minor markers but more
      specific markers including sandal gap, clinodactyly and mid-phalanx hypoplasia of
      the fifth finger were demonstrated. CONCLUSION: About half of the fetuses with
      trisomy 21 had abnormal sonographic findings in the second trimester. The most
      common marker was thickened nuchal fold. Although prenatal ultrasound can not
      permit a definite diagnosis of trisomy 21, about half of them have sonographic
      markers, warranting cytogenetic testing.

PMID- 11336090
TI  - Pregnancy in amniotic band scarred woman.
AB  - Amniotic band syndrome is an uncommon syndrome. The incidence is 1:1,200-1:15,000
      live births. This syndrome is variable malformation. Amniotic band scar of the
      abdomen seen in adulthood is rare. We managed a case of a 23 year-old pregnant
      woman who had suspected amniotic band scar of the abdomen since birth. The uterus
      could expand until term pregnancy despite no intervention. The healthy female
      baby was delivered by cesarean section because of obstetric indication. Both
      mother and baby were in good condition. She and her baby were well at six weeks
      follow-up. We know of no other reported case of maternal abdominal amniotic band
      scar who could continue pregnancy until term with good outcome.

PMID- 11336091
TI  - Malignant peripheral nerve sheath tumor with neurofibromatosis type 1: a 2-case
      report and review of the literature.
AB  - Malignant peripheral nerve sheath tumor is a very rare soft tissue tumor in the
      general population but there is an increased incidence in patients with
      neurofibromatosis type 1. Two cases of malignant peripheral nerve sheath tumor
      associated with neurofibromatosis type 1 whom we were able to follow-up long term
      are presented. Although wide excision was performed successfully in these
      patients, they suffered from local recurrence of the tumors shortly after surgery
      and died with distant metastases. The literature concerning the natural history
      and the management of this specific condition was reviewed.

PMID- 11336092
TI  - Upper aerodigestive tract burn: a case report of firework injury.
AB  - The case of a 46 year-old German man with upper aerodigestive burn by firework
      was reported. He presented with the symptoms and signs of upper airway
      obstruction. Tracheostomy was done and direct laryngoscopy with microscopic
      examination revealed swelling and denudation of the mucosa of the oral cavity and
      supraglottic area. Intravenous steroids and antibiotics were administrated for
      treatment. It is suggested that proper management needs an understanding of the
      mechanism and effect of the corrosive agent. Careful airway management resulted
      in a good outcome in this patient.

PMID- 11336094
TI  - Ethics.

PMID- 11336093
TI  - Midazolam for the treatment of phantom limb pain exacerbation: preliminary
      reports.
AB  - Phantom pain is one of the most difficult intractable pains to manage. The pain
      may result from the imbalance of self-sustaining neural activity that exceeds the
      inhibitory control. The management of acute severe exacerbation of phantom pain
      is extremely difficult. Midazolam acts by potentiation of gamma aminobutyric acid
      (GABA) and enhance the inhibitory action of glycine receptor at spinal neurons.
      We describe two preliminary reports of complete pain relief of severe phantom
      pain exacerbation by intravenous midazolam 3-5 mg.

PMID- 11336095
TI  - Conceptualizing quality of life for elderly people with stroke.
AB  - PURPOSE: Despite increased interest in quality of life (QOL) as an outcome
      measure and as a means of identifying client needs in health care, its
      conceptualisation and the identification of its constituents have been poorly
      researched for elderly people with stroke in Hong Kong. METHOD: This article
      analysed the literature to identify components relevant to the QOL of Chinese
      elderly people with stroke living in the community in Hong Kong. RESULTS: While
      common components of QOL for elderly people with and without stroke and
      regardless of cultural background were identified, a number were specific to an
      elderly Chinese stroke population. CONCLUSION: Recommendations for future
      research have been made with reference to further exploring and validating these
      components for the target population. A clear understanding of these aspects is
      essential for the development of sensitive QOL measures to guide and evaluate
      service delivery to this population.

PMID- 11336096
TI  - A long-term review of severely disabled spina bifida patients using a reciprocal
      walking system.
AB  - PURPOSE: The purpose of the study was to establish long-term compliance of
      paediatric spina bifida patients using a reciprocal walking orthosis, prescribed
      to enhance function and long-term therapeutic benefit. METHODS: Data from current
      clinical notes of 28 spina bifida patients prescribed with the Parawalker
      reciprocal walking orthosis between 1973 and 1984 were compared with those
      established for the purposes of research at the time of original prescription.
      Patients were supplied via an on-going treatment regime by a specialist multi
      disciplinary team. Regular follow-up was an essential element of the clinical
      policy. This enabled effective monitoring of patient performance and
      requirements. It also ensured that accurate data was maintained. Clinical and
      walking performance details were recorded at the time of supply. Current clinical
      notes from routine follow-up reviews for patients in the study were scrutinized
      to establish present status, ambulation performance and medical history. RESULTS:
      Fourteen patients had thoracic lesions the remainder having high, mid lumbar or
      variably diagnosed lesions. The period of use ranged from 4.6 to 18.1 years
      (average = 9.71 years) The orthosis was first prescribed at 3.6 years to 13.9
      years. Discontinuation occurred at between 11.2 and 23.9 years. None of the
      patients suffered a pressure sore or bone fracture. CONCLUSIONS: Long-term
      continuation of reciprocal walking within a controlled treatment regime was
      established. This enabled confirmation that comprehensive health care systems can
      achieve improvements in patient function, together with overall cost savings
      because of the reductions in pressure sores and bone fractures identified for
      such activity.

PMID- 11336097
TI  - Measuring health status of people who are wheelchair-dependent: validity of the
      Sickness Impact Profile 68 and the Nottingham Health Profile.
AB  - PURPOSE: Several questionnaires measuring health status are available, but their
      validity and correspondence between them in people with severe physical
      disabilities is not well known. In this study, the equivalence of the Nottingham
      Health Profile (NHP) and the Sickness Impact Profile 68 (SIP68) was examined.
      METHODS: Patients were 111 people who were wheelchair-bound due to spinal cord
      injuries (45%), rheumatic diseases (27%) or other causes (28%). Internal
      consistency, associations between scales of both questionnaires and with
      criterion variables (reflecting upper and lower extremity function, perceived
      health, social functioning and well-being) were examined. RESULTS: Both the NHP
      and the SIP68 were of acceptable clinimetric quality (Cronbach's alpha 0.53
      0.85). Agreement between scales of both questionnaires was moderate for scales
      reflecting emotional health (0.56) and for scales reflecting physical (0.22-0.68)
      and social functioning (0.28-0.35). CONCLUSION: The NHP reflects perceived
      health, whereas the SIP68 reflects functional health status. In rehabilitation
      research, a careful choice between available health status measures must be made.

PMID- 11336098
TI  - Physiotherapy based on the Bobath concept in stroke rehabilitation: a survey
      within the UK.
AB  - PURPOSE: The Bobath concept is one of the most widely used approaches in stroke
      rehabilitation within Europe. This survey aimed to provide an expert consensus
      view of the theoretical beliefs underlying current Bobath practise in the UK.
      METHOD: Questionnaires (with sections related to: therapist background,
      physiotherapy management, theoretical beliefs and gait re-education strategies
      used) were posted to all senior level physiotherapists working in stroke care (n
      = 1,022). RESULTS: The majority of respondents had more than 10 year's experience
      overall and at least 5 years experience in stroke care. The Bobath concept was
      the preferred approach (n = 67%) followed by an 'eclectic' approach (n = 31%).
      Despite a high level of consensus between groups, there were 13 significant
      differences highlighted between Bobath and 'eclectic' groups related to recovery,
      control of tone, the analysis and facilitation of normal movement and function.
      In summary. Bobath therapists considered that patients needed to have normal tone
      and use normal movement patterns in order to perform functional tasks. They would
      delay patients from performing tasks independently if abnormal tone and movement
      would be reinforced by task practice. They were not opposed to the use of walking
      aids and orthotics. CONCLUSIONS: This survey has raised several issues for debate
      within physiotherapy such as the automatic translation of movement into function,
      carry over outside therapy, and the way in which tasks should be practiced. The
      dominance of the Bobath concept needs to be justified by establishing that it is
      both effective and efficient at achieving its treatment aims of: normalizing
      tone, improving intrinsic recovery of the affected side and function within
      everyday tasks.

PMID- 11336099
TI  - The Catz-Itzkovich SCIM: a revised version of the Spinal Cord Independence
      Measure.
AB  - PURPOSE: To examine the suitability of the revised Spinal Cord Independence
      Measure, the Catz-ltzkovich SCIM, for evaluation of patients with spinal cord
      lesions, as compared to the original SCIM and to the Functional Independence
      Measure (FIM). METHOD: The revised SCIM was applied by paired independent teams
      of occupational therapists, physiotherapists and nurses and the FIM by a single
      nurse. The examiners assigned scores to the functional capabilities of 28
      patients with spinal cord lesions. The scores by the revised SCIM were analysed
      for reproducibility as between the two teams of examiners (interrater
      reliability) and for their correlation with the FIM scores. RESULTS: The
      frequency of identical scoring by two independent examiners (total agreement) was
      80% or higher for 13/18 individual functions listed in the revised SCIM. In the
      self-care category it was 80-99%, as compared to 75-87% before revision. In
      neither bowel management nor bed mobility was there an increase over the original
      SCIM in the frequency of identical scores, despite rephrasing and restructuring
      of the scoring criteria. A high correlation was noted between the paired scores
      for all functions listed as well as for those comprising each of the four
      functional categories (r = 0.90-0.96, p <0.001). The total revised-SCIM scores
      were significantly correlated with those derived by the FIM (r = 0.835, p <
      0.001). CONCLUSIONS: The findings indicate that the newly revised SCIM (Catz
      Itzkovich) is a valid and highly reproducible measure of daily function in
      patients with spinal cord lesions, and is superior to the original SCIM. We
      recommend that it supersede the original SCIM.

PMID- 11336100
TI  - Effects of the aminopeptidase P inhibitor apstatin on bradykinin-induced inositol
      1,4,5-triphosphate in neonatal rat cardiomyocytes.
AB  - We investigated the effect of apstatin (an aminopeptidase P inhibitor) on
      bradykinin-induced inositol 1,4,5-triphosphate (IP3) formation and glucose uptake
      in isolated neonatal rat cardiomyocytes. Apstatin enhanced bradykinin-induced IP3
      formation in a dose-dependent manner. We found that 1 microM Hoe 140 (a
      bradykinin B2-receptor antagonist) significantly decreased the potentiation of
      bradykinin-induced IP3 production by 5 microM apstatin from 781.8+/-67.2 to
      127.4+/-33.0 pmol/mg protein; 5 microM apstatin increased bradykinin-induced
      glucose uptake from 197.0+/-25.5 to 297.3+/-64.0 pmol/h per milligram of protein.
      The stimulation of glucose uptake with apstatin was blocked to 132.5+/-26.2
      pmol/h per milligram of protein by 1 microM Hoe 140. We conclude that apstatin
      stimulates bradykinin-induced IP3 formation and glucose uptake by preventing the
      degradation of bradykinin.

PMID- 11336101
TI  - Safety, tolerability, and pharmacokinetics of an extended-release formulation of
      fluvastatin administered once daily to patients with primary
      hypercholesterolemia.
AB  - Fluvastatin sodium (Lescol, Novartis Pharmaceutical Corp., East Hanover, NJ,
      U.S.A.), a potent 3-hydroxy-3-methylglutaryl coenzyme A (HMG Co-A) reductase
      inhibitor that limits cholesterol biosynthesis, is available as a 40-mg immediate
      release formulation capsule. An extended-release formulation for once-daily
      administration has been developed for patients with primary hypercholesterolemia
      who may benefit from doses higher than 40 mg/day. This phase I study evaluated
      the safety, tolerability, and pharmacokinetics of a new fluvastatin extended
      release formulation at doses ranging from 80-640 mg/day in 40
      hypercholesterolemic patients. After a 2-week dietary stabilization phase,
      patients (Fredrickson type IIa/IIb), 18-55 years of age, were randomly assigned
      to four groups to receive oral fluvastatin extended-release (80, 160, 320, or 640
      mg) or matching placebo once daily for 13 days. Fluvastatin extended-release was
      generally safe and well tolerated at doses of 80-320 mg/day. Within this dose
      range, linear pharmacokinetics was observed after single and multiple dosing. At
      640 mg, fluvastatin extended-release was not well tolerated. Six of the seven
      actively treated patients at this dose experienced adverse events, including
      diarrhea, headache, and clinically relevant elevations in serum transaminase
      concentrations. In addition, nonlinear pharmacokinetics, possibly due to
      saturation of first-pass metabolism, was observed at this dose, causing higher
      than expected serum drug concentrations. Once-daily administration of fluvastatin
      extended-release at doses of 80-320 mg/day was generally safe and well tolerated
      in patients with primary hypercholesterolemia over a 13-day dosing period.

PMID- 11336102
TI  - Reversal of pathophysiologic changes with long-term lisinopril treatment in
      isolated systolic hypertension.
AB  - The purpose of this study was to evaluate in a prospective, double-blind, placebo
      controlled study the effect of long-term (2-year) lisinopril treatment on
      cardiovascular end-organ damage in patients with previously untreated isolated
      systolic hypertension (ISH). All patients with ISH were derived from a population
      screening program. End-organ damage measurements, done initially and after 6 and
      24 months of treatment, included measurements of aortic distensibility and
      echocardiographic left ventricular mass index (LVMI) and diastolic function.
      Blood pressure was measured by office and ambulatory measurements. Of the 97
      subjects with ISH selected from the screening, 62 (30 lisinopril) completed the
      study according to protocol. Office blood pressure decreased in both groups, but
      ambulatory results significantly decreased with lisinopril-treatment only. Aortic
      distensibility increased significantly with lisinopril, as opposed to a decrease
      in placebo-treated subjects. The main effect of increased distensibility occurred
      between 6 and 24 months, whereas ambulatory blood pressure changed mainly in the
      first 6 months of treatment. LVMI decreased in both treatment groups, with a
      significantly higher reduction in lisinopril-treated subjects. Left ventricular
      diastolic function showed no significant changes in either group. The vascular
      pathophysiologic alterations of ISH-a decreased aortic distensibility-can be
      improved with long-term lisinopril treatment, whereas values deteriorate further
      in placebo-treated subjects. These results, in one of the first studies including
      subjects with previously untreated ISH only, indicate that lisinopril treatment
      might favorably influence the cardiovascular risk of ISH.

PMID- 11336103
TI  - Modulation by nucleotides of binding sites for [3H]glibenclamide in rat aorta and
      cardiac ventricular membranes.
AB  - Radioligand binding techniques were employed to determine the modulation by
      nucleotides of the specific [3H]glibenclamide (Gli) binding to rat aortic and
      cardiac ventricular preparations. Saturation analysis revealed a single binding
      site with K(D) value of 31.3 nM and Bmax of 180 fmol/mg wet weight in aortic
      preparations. We also observed that [3H]Gli bound reversibly and specifically to
      cardiac membranes. Unlabeled glibenclamide displaced [3H]Gli-specific binding of
      cardiac membranes completely with K(I) of 54.4 nM. In cardiac membranes,
      adenosine triphosphate (ATP), adenosine diphosphate (ADP), and uridine
      diphosphate (UDP) (from 0.01-5 mM) concentration dependently inhibited [3H]Gli
      binding independent of Mg2+. The values of K(I) were 0.47, 0.22, and 0.58 mM,
      respectively. However, in aortic preparations, [3H]Gli-specific binding was
      increased by ATP of 5 and 10 mM and showed a biphasic response to ADP. At
      concentrations to 1 mM, ADP inhibited binding; above 5 mM, the specific [3H]Gli
      binding was increased. UDP did not alter the binding up to 5 mM. In the presence
      of Mg2+ (20 mM), the inhibitory effects of ATP (0.01-1 mM) or ADP (0.01-5 mM) on
      the binding in cardiac membranes were abolished, whereas the facilitatory effects
      of ATP or ADP in aortic preparations were strengthened. Analysis of kinetics
      showed that the time of [3H]Gli association and dissociation in cardiac and
      aortic preparations was monophasic. The association was delayed with dissociation
      unchanged by ATP, ADP, and UDP of 1 mM, respectively, in cardiac membranes. In
      aorta, however, at the same concentration ATP accelerated association and
      retarded dissociation and vice versa for ADP. Association and dissociation were
      not changed by UDP of 5 mM. We conclude that ATP, ADP, and UDP are all major
      allosteric modulators of K(ATP) channels and they affect the antagonist binding
      to heart (sulfonylurea receptor 2A) and aorta (sulfonylurea receptor 2B)
      differently.

PMID- 11336105
TI  - Effects of canrenone on aorta and right ventricle of the rat.
AB  - Canrenone is a major active metabolite of spironolactone and, in addition to the
      antimineralocorticoid effect, shares with the parent compound the action as a
      partial agonist with respect to ouabain on the Na+-K+ ATPase. We have
      investigated whether canrenone, through its action on Na+-K+ ATPase, reverses rat
      aorta contractions induced by ouabain and has vasorelaxant properties unrelated
      to its interaction with ouabain. Contractile responses of endothelium-deprived
      aorta to 1 mM ouabain, 0.1 microM phenylephrine, 10 microM serotonin, and 60 mM
      K+ were relaxed by canrenone (50-250 microM), with maximum inhibitions of 85.3%,
      55.3%, 56.7%, and 64.2%, respectively. Canrenone shifted to the right the
      concentration-response curve for Ca2+ in depolarized aorta and did not affect the
      response to 10 mM caffeine. In rat right ventricular strips driven at 0.1 Hz,
      canrenone exerted negative inotropic effect. The relaxation of ouabain-induced
      contraction may be due, at least in part, to an interaction between canrenone and
      ouabain on the Na+-K+ ATPase. Inhibition of calcium entry through calcium
      channels either in aorta or ventricles is the most parsimonious hypothesis of
      mechanism underlying the effect of canrenone on contractile responses of rat
      aorta to agonists and high K+ and the negative inotropic effect on ventricular
      strips.

PMID- 11336104
TI  - Doxazosin inhibits monocyte chemotactic protein 1-directed migration of human
      monocytes.
AB  - Monocyte chemotactic protein 1 (MCP-1)-directed transendothelial migration of
      monocytes plays a key role in the early development of atherosclerosis. Migration
      of monocytes requires degradation of extracellular matrices, a process that
      involves matrix metalloproteinases (MMP) and tissue inhibitors of MMPs (TIMP).
      Recent studies suggest that the alpha1-adrenergic receptor antagonist doxazosin
      (Dox) might have antiatherosclerotic effects, although the underlying mechanisms
      are poorly understood. The purpose of the present study was to determine the
      effects of Dox on MCP-1-directed monocyte migration, MMP-9 activity, and TIMP-1
      expression. MCP-1 (50 ng/ml) stimulated migration of human peripheral blood
      monocytes (HPBM) 2.7+/-0.42-fold and THP-1 human monocytes 5.9+/-0.83-fold
      compared with unstimulated control. Dox inhibited MCP-1-induced migration in a
      dose-dependent manner, with a maximal reduction at 10 microM of 69.5+/-5.9% in
      HPBM and 72.2+/-3.2% in THP-1 cells. Dox blocked migration even after
      pretreatment with phenoxybenzamine, an irreversible alpha1-adrenergic receptor
      antagonist (HPBM: phenoxybenzamine 1 microM + Dox 10 microM, 71.9+/-2.2%
      inhibition; THP-1 cells: phenoxybenzamine 1 microM + Dox 10 microM: 78+/-7.7%
      inhibition), suggesting that the antimigratory activity of Dox is mediated
      through a novel mechanism unrelated to its blocking of the alpha1-adrenergic
      receptor. Dox (10 microM) inhibited MMP-9 activity by 67.6+/-10.5%, whereas MMP-9
      protein levels were not affected. Also, Dox increased PMA-induced-tissue
      inhibitor of MMPs-1 (TIMP-1) expression by 134.4+/-6.6%. Dox 10 microM. The
      present study demonstrates a potential novel antiatherosclerotic action of Dox by
      blocking MCP-1-directed monocyte migration, which might be partly mediated by
      inhibition of MMP-9 activity.

PMID- 11336106
TI  - Cardiovascular sympathomimetic amine interactions in rats treated with monoamine
      oxidase inhibitors and the novel oxazolidinone antibiotic linezolid.
AB  - Linezolid (PNU-100766) is a new gram-positive oxazolidinone antibiotic that is
      effective at in vitro concentrations < or =4 microg/ml and in vivo doses < or =10
      mg/kg. Because linezolid also competitively inhibits human monoamine oxidase-A
      (MAO-A; Ki = 55 microM), we monitored its effects on the cardiovascular responses
      to tyramine and amine cold remedies in comparison with standard MAO inhibitors.
      In anesthetized rats, the pressor response to 16 microg i.v. tyramine was
      potentiated by the MAO-A inhibitors clorgyline (0.1-1.0 mg/kg i.v.) and
      moclobemide (5.0-50 mg/kg p.o.), but not by the MAO-B inhibitor selegiline (0.15
      15 mg/kg p.o.). Fifteen milligrams per kilogram intravenous linezolid weakly
      potentiated i.v. tyramine independent of changes in alpha-adrenoceptor
      reactivity, but this effect was not enhanced chronically (90-100 mg/kg/day). In
      conscious rats, 30 mg/kg/day oral linezolid (8 microg/ml plasma concentration)
      minimally affected the pressor response to 20 mg/kg oral tyramine, whereas 100
      mg/kg/day linezolid (20 microg/ml plasma concentration) moderately potentiated
      this response similar to 3 mg/kg per day moclobemide. Linezolid's tyramine
      potentiation was reversible, attenuated by food, and independent of
      pseudoephedrine, phenylpropanolamine, and dextromethorphan interactions. These
      studies demonstrate that high-dose linezolid only moderately potentiates the
      cardiovascular effects of tyramine and validate these models for evaluating such
      MAO inhibitory interactions.

PMID- 11336107
TI  - Acute effects of vitamin C on platelet responsiveness to nitric oxide donors and
      endothelial function in patients with chronic heart failure.
AB  - Chronic heart failure (CHF) is characterized by a prothrombotic state, which may
      relate to increased platelet aggregability, endothelial dysfunction, and
      increased oxidative stress. We investigated the effect of vitamin C in CHF on ex
      vivo platelet aggregation and platelet responsiveness to the anti-aggregatory
      effects of the nitric oxide (NO) donors glyceryl trinitrate (GTN) and sodium
      nitroprusside (SNP). We also examined parameters of oxidative stress and
      endothelial function in patients. In this double-blind, randomized, crossover
      study vitamin C (2 g) or placebo was given intravenously to 10 patients with CHF.
      We measured adenosine 5-diphosphate (ADP)-induced platelet aggregation, flow
      mediated dilatation (FMD) in the brachial artery using ultrasonic wall-tracking,
      and plasma levels of lipid-derived free radicals using electron paramagnetic
      resonance spectroscopy. Vitamin C did not affect ex vivo platelet aggregability
      but enhanced the inhibition of platelet aggregation by SNP (62.7+/-10.2 to 82.7+/
      4.8%, p = 0.03) and tended to increase responses to GTN (40.5+/-9.0 to 53.4+/
      7.3, p = 0.06). The effect of vitamin C on platelet responsiveness to the
      antiaggregatory effects of SNP was inversely related to basal response to SNP (r
      = -0.9, p < 0.01); a similar trend was observed with GTN (r = -0.6, p = 0.1).
      Vitamin C also increased FMD (1.9+/-0.6 to 5.8+/-1.5%, p = 0.02) and reduced
      plasma lipid-derived free radicals by 49+/-19% (p < 0.05). In patients with CHF
      acute intravenous administration of vitamin C enhances platelet responsiveness to
      the anti-aggregatory effects of NO donors and improves endothelial function,
      suggesting a potential role for vitamin C as a therapeutic agent in CHF.

PMID- 11336108
TI  - Coronary vasomotor and cardiac electrophysiologic effects of diadenosine
      polyphosphates and nonhydrolyzable analogs in the guinea pig.
AB  - Platelet activation in heart disease is important owing to the effects of
      platelet-derived compounds on myocardial perfusion and cardiac electrophysiology.
      Diadenosine polyphosphates are secreted from platelets and present in the
      myocardium, but their electrophysiologic and vasomotor effects are incompletely
      understood. We used isolated guinea-pig hearts to study the effects of
      diadenosine triphosphate (Ap3A), tetraphosphate (Ap4A), pentaphosphate (Ap5A),
      and hexaphosphate (Ap6A) (10 pM-0.1 mM), comparing their actions to those of
      adenosine, adenosine triphosphate, and non-hydrolyzable Ap4A and Ap5A analogs.
      Diadenosine polyphosphates (0.1 nM-0.1 microM) transiently reduced coronary
      perfusion pressure, which recovered during the continued presence of the
      compounds. At concentrations greater than 0.1 microM effects were maximal and
      sustained (perfusion pressure decreased from 36.5+/-3.4 to 18.6+/-2.5 mm Hg, p <
      0.001, with 1 microM Ap4A). The changes in action potential duration and
      refractory period developed slowly but were maintained (0.1 nM-1 microM). With 1
      nM Ap4A, action potential duration increased from 170.6+/-2.6 to 187.3+/-3.8 ms,
      p < 0.05, and refractory period increased from 138.5+/-1.6 to 147.9+/-2.0 ms, p <
      0.05. Ap4A and its analog reduced QRS duration (from 24.7+/-1.1 to 13.9+/-1.6 ms
      with 1 microM Ap4A, p < 0.05). P2-purinergic (adenosine triphosphate) receptor
      antagonism (suramin) reduced perfusion pressure but was without
      electrophysiologic effect. Other changes in coronary perfusion pressure and
      electrophysiologic variables associated with Ap4A were not seen in the presence
      of suramin. P1-(adenosine) antagonism (8-[p-sulfophenyl]theophylline) attenuated
      the electrophysiologic effects only. Diadenosine polyphosphates have potent
      cardiac electrophysiologic and coronary vasomotor effects via purinergic
      receptors, suggesting an important role during platelet activation in acute
      coronary syndromes.

PMID- 11336109
TI  - Mechanisms of relaxation induced by angiotensin II in isolated canine and human
      uterine arteries.
AB  - The present study aimed to determine the action of angiotensin II and to
      pharmacologically analyze mechanisms of their action in isolated uterine
      arteries. Canine and human uterine artery strips were suspended in Ringer-Locke
      solutions for isometric tension recording. Canine and human uterine arteries
      responded to angiotensin II with transient contraction followed by relaxation,
      which were abolished by losartan, an AT1 receptor subtype antagonist.
      Cyclooxygenase inhibitors augmented the contraction and abolished the relaxation.
      The relaxation was also abolished or suppressed by tranylcypromine, a
      prostaglandin I2 synthesis inhibitor. The relaxant response of dog uterine
      arteries to angiotensin II was partially suppressed by endothelium denudation but
      was not influenced by nitric oxide synthase inhibitor. Conversely, the response
      of human uterine arteries to the peptide was unaffected by endothelium
      denudation. The antagonists used and endothelium denudation did not inhibit the
      relaxation caused by a prostaglandin I2 analogue. It appears that the angiotensin
      II-induced relaxation is mediated by vasodilator prostaglandins, possibly
      prostaglandin I2, released from both endothelium and subendothelial tissues in
      dog uterine arteries. In human uterine arteries, the vasodilator prostaglandin is
      released from subendothelial tissues due to AT1 receptor stimulation by the
      peptide.

PMID- 11336110
TI  - Vasorelaxant effects of cardamonin and alpinetin from Alpinia henryi K. Schum.
AB  - The vascular effects of cardamonin and alpinetin from Alpinia henryi K. Schum.
      were examined in the rat isolated mesenteric arteries. 1H and 13C nuclear
      magnetic resonance spectra showed that cardamonin is present in trans-form, and
      single-crystal radiographic structure revealed that alpinetin is present in S
      configuration. Both cardamonin and alpinetin produced a rightward shift in the
      concentration-response curve for phenylephrine in a noncompetitive manner, and
      they induced relaxation of phenylephrine-preconstricted arteries with respective
      mean inhibitory concentrations (IC50) of 9.3+/-0.6 microM and 27.5+/-2.8 microM.
      Both compounds also relaxed arteries preconstricted by endothelin I or U46619.
      Their relaxant effects were decreased in endothelium-removed rings. Pretreatment
      with N(G)-nitro-L-arginine methyl ester or methylene blue inhibited relaxation
      induced by both agents, and pretreatment with L-arginine reversed the effect of
      N(G)-nitro-L-arginine methyl ester on cardamonin-induced endothelium-dependent
      relaxation. The relaxant effects of cardamonin and alpinetin were unaffected by
      indomethacin (3 microM). Cardamonin and alpinetin inhibited 60 mM K+-induced
      contraction with respective IC50 of 11.5+/-0.3 microM and 37.9+/-3.6 microM. In
      addition, both agents inhibited the transient contraction induced by 3 microM
      phenylephrine or by 10 mM caffeine in Ca2+-free Krebs solution. Finally, these
      two agents also concentration dependently relax the arteries preconstricted by 1
      microM phorbol 12,13-diacetate in Ca2+-free Krebs solution. These results
      indicate that purified cardamonin and alpinetin from A. henryi K. Schum. relaxed
      rat mesenteric arteries through multiple mechanisms. They induced both
      endothelium-dependent and -independent relaxation; the former is likely mediated
      by nitric oxide whereas the latter is probably mediated through nonselective
      inhibition of Ca2+ influx and intracellular Ca2+ release and inhibition of the
      protein kinase C-dependent contractile mechanism.

PMID- 11336112
TI  - A peptide analogue of thrombin receptor-activating peptide inhibits thrombin and
      thrombin-receptor-activating peptide-induced vascular smooth muscle cell
      proliferation.
AB  - The serine protease thrombin, in addition to its pivotal role in the coagulation
      cascade, plays an important role in the development of atherosclerosis and
      restenosis by inducing smooth cell proliferation. Thrombin exerts its cellular
      effects mainly by cleaving its own receptor, leaving a new NH2-terminus that can
      act as a tethered ligand to activate the thrombin receptor. Peptides derived from
      the new NH2-terminus are able to fully activate thrombin receptor and mimic
      cellular effects of thrombin. Peptides with structural similarities to the
      tethered ligand have been tested for their ability to prevent thrombin- and
      tethered ligand-induced platelet aggregation and thrombus formation. We
      synthesized a peptide with multiple alanine substitutions in both critical and
      noncritical residues of tethered ligand that specifically inhibited platelet
      aggregation induced by thrombin and thrombin receptor-activating peptide and
      prevented thrombus formation in a rabbit thrombosis model. In the present study
      we demonstrate that this peptide inhibited only thrombin- and tethered ligand
      induced human vascular smooth muscle cell proliferation as determined by (3H)
      thymidine incorporation and has no effect on platelet-derived growth factor and
      serum-induced smooth muscle cell proliferation. The inhibitory effect of this
      peptide is dependent on the concentration of the antagonist used and length of
      preincubation time. The possible mechanism by which this peptide exerts its
      inhibitory effect may by desensitizing the thrombin receptor. The results of the
      present study suggest that apart from being antithrombotic, tethered ligand
      antagonist peptides can also act as antiatherosclerotic or antirestenotic agents.

PMID- 11336111
TI  - The canine Purkinje fiber: an in vitro model system for acquired long QT syndrome
      and drug-induced arrhythmogenesis.
AB  - Torsade de pointes is a rare but potentially fatal ventricular arrhythmia
      associated with drug-induced delayed repolarization and prolongation of the QT
      interval. To determine if the arrhythmogenic potential of noncardiac drugs can be
      assessed in vitro, we evaluated the effects of 12 drugs on the action potential
      duration (APD) of cardiac Purkinje fibers and compared results with clinical
      observations. APD changes in canine and porcine fibers were evaluated under
      physiologic conditions (37 degrees C, [K+]0 = 4 mM) using standard microelectrode
      techniques. Six of seven drugs associated with QT prolongation or torsade de
      pointes in man (cisapride, erythromycin, grepafloxacin, moxifloxacin, sertindole,
      and sotalol) affected concentration-dependent prolongation of the APD in canine
      fibers during slow stimulation (2-s basic cycle length), attaining greater than
      15% prolongation at high concentrations (> or = 10-fold clinically encountered
      plasma levels). Each of five drugs not linked clinically to QT prolongation and
      torsade de pointes (azithromycin, enalaprilat, fluoxetine, indomethacin, and
      pinacidil) failed to attain 15% prolongation, with fluoxetine, indomethacin, and
      pinacidil abbreviating the APD. Drugs eliciting the greatest prolongation also
      demonstrated prominent reverse rate-dependent effects. The antihistamine
      terfenadine (linked to dose-dependent QT prolongation and torsade de pointes
      clinically) only minimally prolonged the APD in canine and porcine fibers (and
      exerted no effect on midmyocardial fibers from left ventricular free wall) at
      supratherapeutic concentrations. On the basis of concentration-dependent APD
      prolongation and reverse rate-dependent effects, this Purkinje fiber model
      detects six of seven drugs linked clinically to acquired long QT syndrome and
      torsade de pointes, and clears each of five drugs not associated with
      repolarization abnormalities (overall 92% accuracy), validating the utility of
      this Purkinje fiber model in the preclinical evaluation of QT prolongation and
      proarrhythmic risk by noncardiac drugs.

PMID- 11336113
TI  - Influence of endothelium in dose-dependent inhibition and potentiation by
      isoniazid of isosorbide dinitrate relaxation of rat aorta.
AB  - The influence of in vivo administration of isoniazid on the relaxant effect of
      isosorbide dinitrate was determined by pretreating rats with various doses of
      isoniazid and obtaining concentration-response curves to isosorbide dinitrate in
      aortic rings from these animals. In rings with endothelium, isoniazid potentiated
      responses to isosorbide dinitrate at doses of 10, 30, and 100 mg/kg; 3 and 300
      mg/kg were without effect. In endothelium-denuded preparations, potentiation was
      present only at 10 mg/kg; 3 and 300 mg/kg inhibited relaxation. Other experiments
      indicated that isoniazid potentiation was prevented by pyridoxine, was reproduced
      with theophylline, and did not occur with 3-morpholinosydnonimine or papaverine.
      These results were deemed compatible with the hypothesis that isoniazid inhibits
      transsulfuration of homocysteine and causes its accumulation in vascular smooth
      muscle and endothelial cells, where it functions as a thiol intermediate and
      leads to enhanced bioactivation of isosorbide dinitrate. Potentiation appeared to
      occur only with moderate increases of homocysteine.

PMID- 11336114
TI  - Introduction: Tobacco, human disease, and the role of the dental profession.

PMID- 11336115
TI  - Tobacco use and oral disease.
AB  - Tobacco use is a risk factor for oral cancer, oral mucosal lesions, periodontal
      disease and impaired healing after periodontal treatment, gingival recession, and
      coronal and root caries. Available evidence suggests that the risks of oral
      diseases increase with greater use of tobacco and that quitting smoking can
      result in decreased risk. The magnitude of the effect of tobacco on the
      occurrence of oral diseases is high, with users having many times the risk of non
      users. There is a clear benefit to quitting tobacco use. The risks of oral cancer
      and periodontal disease decline as time from cessation increases, and some oral
      mucosal lesions may resolve with cessation of smokeless tobacco use. Smoking
      accounts for half of periodontal disease and three-fourths of oral cancers in the
      United States. Because tobacco accounts for such a high proportion of these
      diseases, comprehensive tobacco control policies are required to make progress in
      reducing the burden of tobacco-related oral diseases. Effective treatments to
      prevent tobacco use and increase cessation are available and need greater
      implementation. Dental practices may provide a uniquely effective setting for
      tobacco prevention and cessation.

PMID- 11336116
TI  - Impact of tobacco use on periodontal status.
AB  - This article reviews the effects of smoked and smokeless tobacco on periodontal
      status, including the impact of smoking on periodontal therapy and potential
      mechanisms for the adverse effects of tobacco on the periodontium. Approximately
      half of periodontitis cases have been attributed to either current or former
      smoking. Both cigar and cigarette smokers have significantly greater loss of bone
      height than nonsmokers, and there is a trend for pipe smokers to have more bone
      loss than nonsmokers. Unlike smokers, who experience widespread periodontal
      destruction, the most prevalent effects of smokeless tobacco are localized to the
      site of placement, in the form of gingival recession and white mucosal lesions.
      Smoking has an adverse effect on all forms of periodontal therapy, and up to 90
      percent of refractory periodontitis patients are smokers. The pathogenesis of
      smoking-related periodontal destruction has been attributed to alterations in the
      microflora and/or host response. Some data indicates that smoking may increase
      levels of certain periodontal pathogens, but there is more evidence that smoking
      has a negative effect on host response, such as neutrophil function and antibody
      production. An encouraging finding is that periodontal disease progression slows
      in patients who quit smoking and that these individuals have a similar response
      to periodontal therapy as nonsmokers. The facts presented in this paper will
      assist dental health professionals in treatment-planning decisions and provide
      them with important information to share with patients who use tobacco products.

PMID- 11336117
TI  - Tobacco use and oral leukoplakia.
AB  - The increase in cancer mortality throughout the world justifies the study of its
      causes and development. Hungary has the highest mortality rate from oropharyngeal
      cancer out of forty-six countries. Tobacco use is implicated in the development
      of oral cancer, and oral leukoplakia as well. The aim of the study was to give an
      overview of the connection between tobacco use and oral leukoplakia, considering
      the epidemiologic patterns of tobacco habits, the prevalence of smoking in oral
      leukoplakia, and the effect of smoking on clinically healthy oral mucosa with
      special respect to central Europe and Hungary. In the data, strong evidence has
      been found for the role of smoking in the development of both oral cancer and
      oral leukoplakia. Epidemiologic patterns of cigarette smoking show a steep
      increase in central European countries. Cross-sectional studies show a higher
      prevalence rate of leukoplakia among smokers, with a dose-response relationship
      between tobacco use and oral leukoplakia, and intervention studies show a
      regression of the lesion after stopping the smoking habit.

PMID- 11336118
TI  - Tobacco use and oral cancer: a global perspective.
AB  - For both genders, cancer of the mouth and pharynx ranks sixth overall in the
      world; it is also the third most common site among males in developing countries.
      In industrialized countries, men are affected two to three times as often as
      women, largely due to higher use of alcohol and tobacco. Ethnicity strongly
      influences prevalence due to social and cultural practices, as well as
      socioeconomic differences. In population terms, survival rates around the world
      show little improvement. In terms of etiology, the effects of tobacco use, heavy
      alcohol consumption, and poor diet together explain over 90 percent of cases of
      head and neck cancer. All forms of tobacco represent risk factors for oral
      cancer, but on present evidence, snuff habits as they exist in Scandinavia and
      probably in the United States carry lower risks of serious health hazards,
      including oral cancer. Alcohol synergizes with tobacco as a risk factor for all
      upper aerodigestive tract SCC: this is super-multiplicative for the mouth,
      additive for the larynx, and between additive and multiplicative for the
      esophagus. The increase in oral cancer in the Western world has been related to
      rising alcohol use.

PMID- 11336119
TI  - Hypnosis, behavioral theory, and smoking cessation.
AB  - Although nicotine replacement and other pharmacological treatments head the list
      of popular interventions for smoking cessation, approaches based on psychology
      can also assist smokers. Hypnosis, suggestion, and behavior therapies have been
      offered to patients and studied experimentally for several decades. Although no
      single psychological approach has been found to be superior to others,
      psychological interventions contribute significantly to successful treatment
      outcome in smoking cessation. This article describes common hypnotic and
      behavioral approaches to smoking cessation and critically reviews some of the
      findings from clinical and experimental research studies. The authors also offer
      suggestions regarding treatment and future research.

PMID- 11336121
TI  - Tobacco cessation through dental office settings.
AB  - There is increasing interest in broadly inclusive public health interventions
      that involve low-cost, self-help materials and minimal support from
      professionals. Dental health care workers (DHCWs) are a largely untapped resource
      for providing advice and brief counseling to tobacco-using patients, and there
      are good reasons to believe that they can be effective in this role. The results
      of our randomized clinical trials have shown that a brief dental office-based
      intervention can be effective in helping smokeless tobacco users to quit and
      smokers to reduce their use and become more ready to quit. A third clinical trial
      tested the effectiveness of two methods of disseminating the smokeless tobacco
      intervention to DHCWs throughout the western United States. Workshops were more
      effective than self-study in effecting behavior change, although our analyses
      indicate that self-study was more cost-efficient. These studies have demonstrated
      the viability of using dentists and dental hygienists to provide brief cessation
      advice and supportive materials in the context of regular oral health visits to
      encourage their patients to quit. The results of these studies also support the
      timeliness of further dissemination and diffusion of this program to
      practitioners, dental schools, and dental hygiene programs.

PMID- 11336120
TI  - The feasibility and efficacy of tobacco use prevention in orthodontics.
AB  - SMILES PLUS was the first study to extend the clinician-delivered logic model to
      prevention of tobacco use among adolescents. This multi-site trial with 154
      participating offices, based on social learning theory and a behavioral
      ecological model, was designed to test whether orthodontists can prevent preteens
      from initiating smoking. The study found that orthodontists do not automatically
      adhere to anti-tobacco prevention services. Social learning variables can enhance
      both adherence to counseling guidelines and content of counseling to increase
      prevention effects. Providing financial incentives, tracking prescriptions,
      prompting positive feedback from patients, and adopting anti-tobacco counseling
      models in the office are likely to enhance anti-tobacco preventive services.
      Training orthodontists to be comfortable when advising nonsmoking youth not to
      start and to use social consequences to justify youth avoidance of tobacco might
      increase adherence to protocols and make their counseling more powerful.
      Adolescent smokers prior to intervention were more likely to start other risky
      behaviors later. Preventing tobacco use may halt additional risk behaviors and
      thereby reduce morbidity/mortality even more than expected from tobacco control
      alone. New and refined clinical trials should be conducted to determine the most
      effective interventions for adolescent tobacco control by clinicians.

PMID- 11336122
TI  - The question of cost: reimbursement and remuneration.
AB  - Dentists and the dental team have been encouraged to become an important part of
      the effort to curb tobacco use. Many health insurance policies, however, do not
      cover tobacco cessation programs, especially by dentists. The generosity of
      insurance for tobacco cessation has been found to influence the use of these
      programs. The dental profession can help by: 1) training more dental students,
      dental hygienists, and dental practitioners to provide tobacco cessation
      counseling; 2) increasing the number of practices routinely monitoring tobacco
      use and providing tobacco cessation programs; 3) increasing the utilization of
      the available procedure codes for tobacco cessation, whether it is a covered
      service or not; and 4) stimulating demand for more tobacco cessation coverage by
      employees.

PMID- 11336123
TI  - Tobacco cessation, the dental profession, and the role of dental education.
AB  - This article describes the development of a comprehensive, interdisciplinary,
      tobacco cessation program based on twenty years of experience at the Indiana
      University (IU) School of Dentistry. It reviews the relationship between tobacco
      use and oral health, the nature of nicotine addiction and cessation approaches
      involving nicotine replacement therapy. In the early 1980s, tobacco control
      curriculum and cessation guidelines were introduced at the IU School of Dentistry
      and cooperative efforts initiated with other U.S. and Canadian dental schools.
      During the past decade, an interdisciplinary Nicotine Dependence Program has been
      developed to serve outpatients receiving treatment at all hospitals on the IU
      Medical Center campus. It is hoped that the models described here will be of
      value to other dental schools developing educational curricula and tobacco
      control and cessation programs.

PMID- 11336124
TI  - Tobacco prevention and control in dental practice: the future.
AB  - Tobacco use adversely affects oral health and dental care. Globally, the health
      consequences of tobacco use are worsening, particularly those caused by cigarette
      smoking. Concerned government and nongovernmental organizations are attempting to
      contain the transnational tobacco companies' promotion of tobacco use and its
      disregard for the serious health consequences. Dependence prevents most tobacco
      users from easily breaking free from their high-risk behavior. Evidence-based
      clinical treatment methods that substantially increase quit rates are available
      in the Public Health Service clinical practice guideline, Treating Tobacco Use
      and Dependence. Guideline recommendations are as useful to dental clinicians as
      to other health care disciplines. Dental educators have a strategic role in
      ensuring that clinicians are well informed and are skilled in and committed to
      providing tobacco prevention and cessation services to their patients. Dental
      organizations must identify and overcome perceived and real clinician and
      practice barriers to adopting essential cessation services. The dental profession
      is in an excellent position to play a major role in several emerging issues, such
      as helping the public and policymakers understand the chronic nature of tobacco
      dependence and supporting cessation services for all people, particularly
      pregnant women and youths. Such messages should be presented in terms that
      resonate with the public because tobacco industry activities and products
      continue to undermine well-being, the health economy, and individual self
      directed behavior of choice.

PMID- 11336125
TI  - Psychiatric morbidity in a community sample of Arab children with asthma.
AB  - To determine the extent of psychiatric morbidity among Arab schoolchildren with
      asthma in the United Arab Emirates, we surveyed a stratified community sample of
      schoolchildren (6-13 years) using the Rutter questionnaire (teachers' and
      parents' versions). Comparisons were made between children with asthma and
      controls matched for age, sex, and school. About 16 per cent of children with
      asthma were simultaneously reported by parents and teachers to show significant
      psychopathology. Rates of disturbance were significantly higher in asthmatics
      than controls. Unexpectedly, the psychopathology was predominantly of the
      behavioral type. Cultural factors may account for this unconventional feature.

PMID- 11336126
TI  - Outcome of cardiopulmonary resuscitation in hospitalized African children.
AB  - The outcome of cardiopulmonary resuscitation at the research ward of the Kenya
      Medical Research Institute is reviewed. The outcome for respiratory arrest was 15
      per cent (95 per cent CI 6.6-27) to discharge, and worse for cardiorespiratory
      arrest with no survival. The illnesses leading to cardiopulmonary arrest and
      causes for the disappointing outcome are discussed.

PMID- 11336127
TI  - Heterogeneity of the cystic fibrosis phenotype in a large kindred family in Qatar
      with cystic fibrosis mutation (I1234V).
AB  - Twenty-nine subjects (17 families) with cystic fibrosis belonging to the same
      Bedouin tribe were screened for cystic fibrosis transmembrane regulator gene
      mutations (CFTR). Homozygous I1234V mutation in exon 19 was identified in all
      families with a relatively high rate of consanguinity (96.6 per cent). The
      homozygous I1234V mutation tended to present with a variable degree of pulmonary
      disease, pancreatic insufficiency and electrolyte imbalance. Homozygous I1234V
      was found to be a common mutation in the studied Bedouin tribe in Qatar.

PMID- 11336128
TI  - Transient pseudohypoparathyroidism and neonatal seizure.
AB  - The case of a neonate is presented who had late onset seizure associated with
      hypocalcemia, hyperphosphatemia, and raised parathyroid hormone. The infant did
      not have any stigmata of pseudohypoparathyroidism. The hypocalcemia was initially
      resistant to calcium therapy, but responded to vitamin D analog therapy. The
      diagnosis of 'transient neonatal pseudohypoparathyroidism' was entertained, as
      the infant remained stable and seizure-free with normal serum biochemistry during
      8 months of follow-up.

PMID- 11336129
TI  - Type II Gaucher disease: compound heterozygote with RecNciI and L444P mutations.
AB  - We report the phenotype and genotype of an Indonesian Chinese boy with type II
      Gaucher disease. He had a unique presentation of recurrent cyanosis from
      laryngospasm. He was compound heterozygous for L444P/L444P + A456P + V460V. There
      have been few reports of this heterozygosity and its phenoptype. This genotype
      phenotype correlation will be important for physicians in genetic counselling.
      Type II Gaucher disease in Southeast Asia may not be as rare as was perceived,
      but may be a condition that is under-reported. The success of our technique
      together with the results have made it possible for us to perform prenatal
      diagnosis and carrier detection for the family.

PMID- 11336130
TI  - Partial exchange transfusion as an adjunct to the treatment of severe falciparum
      malaria in children.

PMID- 11336131
TI  - HIV seroprevalence by ELISA in high risk Indian children and their presentation.

PMID- 11336132
TI  - Serum interleukin-2 and interleukin-6 levels in zinc deficiency.

PMID- 11336133
TI  - Plasma zinc levels in patients with iron-deficiency anemia.

PMID- 11336134
TI  - Helicobacter pylori seropositivity in children with diabetes mellitus type 1.

PMID- 11336135
TI  - Screening of hemoglobinopathies in Kahramanmaras Province (Turkey) situated in a
      high prevalence area.

PMID- 11336136
TI  - Clinical audit and the measurement of blood glucose.

PMID- 11336137
TI  - Impact of beta-carotene supplementation through red palm.
AB  - A 10-month long feeding trial was conducted to assess the impact of beta-carotene
      supplementation through red palm oil (RPO) with the focus on vitamin A status,
      morbidity status and acceptability of an RPO-incorporated noon-meal as a dietary
      supplement among two cohorts of 409 (experimental) and 346 (control) preschool
      children in two southern districts of rural Tamil Nadu, selected by stratified
      random sampling. Information was gathered on ocular symptoms of vitamin A
      deficiency and anthropometry, and blood samples were drawn at baseline and final
      rounds for estimation of serum beta-carotene, retinol and tocopherol. Data about
      Socioeconomic Status (SES) were collected once during the study period, while
      information on attendance, consumption and morbidity was recorded by preschool
      teachers. The results showed the following. 1. Significant improvement in the
      vitamin A status of children in terms of disappearance of Bitot's spots (50.0 per
      cent) in the experimental group vs. 28.0 per cent in the control group. 2. After
      feeding of RPO, incidence rate of new Bitot's spots cases was low at 2.13 in the
      experimental children vs. 4.78 in control children. 3. Marked improvement in the
      serum beta-carotene levels after 10 months of feeding. 4. RPO is acceptable to
      children as an edible grade oil as there is no perceptible difference in the
      consumption pattern between experimental and control children.

PMID- 11336138
TI  - Echocardiographic characteristics of patients with sickle cell anaemia in
      Sergipe, Brazil.
AB  - This study describes the cardiac size and function of patients with sickle cell
      anaemia, in Segipe, Brazil, and its association to the clinical severity,
      duration of illness and haemoglobin levels. Heart measurements were obtained by
      echocardiography from 38 children and adolescents and compared to international
      reference values. Sickle cell patients had increased left atrial and ventricular
      dimensions in systole and an increased end diastolic septal and left ventricular
      free wall thickness. These findings correlated with age. There were no
      abnormalities in the ejection or shortening fractions. These results suggest
      early haemodynamic changes with progressive cardiac chamber dilation and
      diastolic dysfunction that become increasingly abnormal with growth.

PMID- 11336140
TI  - Determination of heavy metal contents in human colostrum samples by
      electrothermal atomic absorption spectrophotometry.
AB  - Determination of lead, cadmium, nickel, chromium, manganese and copper levels in
      colostrum samples (n = 30), collected from middle-class mothers, was carried out
      by electrothermal atomic absorption spectrophotometer (ETAAS) with Zeeman effect
      background correction using a tungsten-palladium-citric acid chemical modifier
      mixture. A wet-ashing procedure was applied to dissolve the samples and to remove
      the fat. The graphite furnace temperature programme for analytes determined by
      ETAAS was studied, and the optimum pyrolysis temperatures of Pb, Cd, Ni, Cr, Mn
      and Cu were determined in the presence of the modifier mixture. Detection limits
      of Pb, Cd, Cu, Mn and Cr were determined using a modifier mixture solution. Zinc
      and iron levels were determined by Zeeman flame atomic absorption spectrometer (F
      AAS). Heavy metal levels (mean values) found in colostrum samples were 14.6
      microg/l of Pb, 2.8 microg/l of Cd, 27.8 microg/l of Ni, 8.6 microg/l of Cr, 43.2
      microg/l of Mn, 278 microg/l of Cu, 12.9 mg/l of Zn, and 3.5 mg/l of Fe. These
      metal levels were compared with results from other studies in different
      countries.

PMID- 11336139
TI  - Endoscopic and histopathological evaluation of preschool children with chronic
      diarrhoea.
AB  - Fifty-seven children with chronic diarrhoea, aged 1-5 years, were studied.
      Protein-energy malnutrition was present in 49 (85.9 per cent) children. Anaemia
      (89.5 per cent), presence of mucus and blood in stool (66.6 per cent), abdominal
      distension (52.6 per cent), and abdominal pain (28.1 per cent) were the common
      clinical findings at admission. The enteropathogens isolated from the stool of
      68.4 per cent of patients were Escherichia coli (19.3 per cent), Candida albicans
      (12.3 per cent), E. histolytica (8.8 per cent), and Giardia lamblia (7 per cent).
      Secondary lactose intolerance was present in 21 per cent of children, endoscopic
      appearance was abnormal in 23.3 per cent of children and the commonest finding
      was chronic duodenitis (16.7 per cent). Abnormal histopathology was observed in
      73.3 per cent of cases and villous atrophy with mononuclear cell infiltration
      (56.7 per cent) was the most common abnormality detected. The mean duration of
      diarrhoea had no impact on endoscopic appearance but it significantly affected
      the histopathological changes. However, no correlation was found in endoscopic
      and histopathological lesions in relation to malnutrition and aetiological
      agents.

PMID- 11336141
TI  - Risk factors associated with death in children admitted to a paediatric intensive
      care unit.
AB  - The aim of this study was to identify fatal risk factors for children admitted to
      the paediatric intensive care unit of the Instituto Materno Infantil de
      Pernambuco, a referral hospital in Recife, a city in the north-east of Brazil. A
      survey was performed from June 1996 to January 1997. Risk was quantified by the
      crude and adjusted odds ratio. The 95 per cent confidence interval, likelihood
      ratio statistics, and the probability (p < 0.05) value were used to test for
      statistical significance. An association was established between death in
      children admitted to the paediatric intensive care unit and: (1) age below 2
      years old; (2) use of mechanical ventilation and central venous catheter; (3)
      presence of hospital-acquired infection; (4) length of hospital stay of 2 days or
      less; and (5) Class 4 clinical severity, according to the Clinical Classification
      System (CCS). These results allow the identification of the children with a
      greater risk of death and may contribute to improvements in handling groups of
      patients with poor prognosis.

PMID- 11336142
TI  - Bioelectrical impedance analysis of the body composition of Nigerian children
      with calcium-deficiency rickets.
AB  - Children with calcium-deficiency rickets experience increased urinary excretion
      of both essential and non-essential amino acids compared to non-rachitic children
      of the same age. Chronic wastage of amino acids into the urine could lead to a
      deficit in fat-free mass (FFM) in rachitic children. We therefore determined the
      FFM of children with calcium-deficiency rickets in northern Nigeria using
      bioelectrical impedance analysis. Because of the leg deformities present in the
      rachitic subjects, we calculated a 'corrected' height for each rachitic subject
      using the relationship between arm length and height in non-rachitic subjects
      over the same age range (r = 0.94). A total of 28 children (4 male and 24
      female), 2-9 years of age with calcium-deficiency rickets and an equal number of
      age- and gender-matched controls were recruited into the study. Resistance and
      reactance measurements were obtained for all subjects and the total body water
      was calculated using age-specific equations. FFM was then calculated using age-
      and gender-specific hydration constants. No significant differences were found in
      the weights or FFM between the rachitic subjects and the controls (8.41 kg +/-
      2.19 vs. 8.85 kg +/- 1.90, respectively). We conclude that chronic urinary
      wastage of amino acids by rachitic children does not result in a deficit in FFM.

PMID- 11336143
TI  - Neonatal morbidity and care-seeking behaviour in rural Bangladesh.
AB  - The present study was undertaken to assess the pattern of reported neonatal
      morbidity and the care-seeking behaviour for neonates in rural Bangladesh. Data
      were collected from 1511 women who had live births during January 1996-August
      1998 in four rural subdistricts, which are the field sites of the Operations
      Research Project of the International Centre for Diarrhoeal Disease Research,
      Bangladesh. A structured questionnaire was used to collect information from the
      mothers who were interviewed in their homes. Forty-nine per cent of the neonates
      were reported to have suffered from some kind of morbidity. Fever was the most
      common morbidity reported in the study population (21 per cent), followed by
      breathing difficulty (11 per cent). Birth order, complications during pregnancy,
      and/or delivery and death of a sibling were found to be significantly associated
      with reported neonatal morbidity. Eighty-seven per cent of the mothers sought
      care for their newborns. Some were taken to several different providers, the
      commonest being homeopaths (38 per cent) and village doctors (37 per cent).
      Seventeen per cent were taken to trained providers, and only 5 per cent to
      government health facilities. Seeking care from trained providers was found to be
      associated with the gender of the neonate, birth order, antenatal care of the
      mother from trained providers, father's education and monthly expenditure of the
      family. The results of this study suggest that efforts should be made to raise
      community awareness regarding neonatal morbidity, the importance of seeking care
      from trained personnel and the availability of services for these conditions.

PMID- 11336144
TI  - Radial forearm fasciocutaneous free-tissue transfer in ankle and foot
      reconstruction: review of 17 cases.
AB  - Seventeen patients who underwent soft-tissue reconstruction of various anatomic
      regions of the foot and ankle, using the radial forearm fasciocutaneous free
      flap, are reported. The procedures were performed between January, 1992 and
      December, 1998. Indications for reconstruction included diabetes and/or vascular
      insufficiency (four patients), soft-tissue defects (six patients), and chronic
      osteomyelitis (seven patients). The weight-bearing surface of the foot was
      involved in 16 patients. Defects ranged in size from 35 to 206 cm2 (mean: 86.2
      cm2). At a mean follow-up of 3.8 years, the radial forearm flap was successful in
      all cases (100 percent). Flap complications included superficial infection (three
      patients), and minor wound dehiscence at the flap-leg-skin interface (two
      patients). Recurrent ulceration occurred in two patients; both were diabetics
      with weight-bearing flaps. Donor-site complications included partial skin graft
      loss with tendon exposure in one patient, which healed with conservative
      management. Recurrent or persistent osteomyelitis was not demonstrated in any of
      the patients. Of the 16 patients with weight-bearing flaps, 12 were ambulatory,
      three had limited ambulation, and one was non-ambulatory. Three patients required
      modified shoes. No debulking of the transferred flaps was necessary. The radial
      forearm flap is one of the preferred flaps for reconstruction of moderate-sized
      ankle and foot defects, for weight-bearing surfaces, and in the treatment of
      osteomyelitic and diabetic wounds. It meets most of the anatomic prerequisites
      for an ideal foot coverage; it also facilitates the restoration of normal foot
      contour, allowing patients to wear ordinary shoes. The flap provides a durable
      and stable weight-bearing plantar surface during ambulation, and achieves
      excellent aesthetic results; when used as a neurosensory flap, it permits
      adequate reinnervation.

PMID- 11336145
TI  - One-bone forearm formation using vascularized fibula graft for massive bone
      defect of the forearm with infection: case report.
AB  - Massive long-bone defects of greater than 6 cm are difficult to treat with
      conventional bone grafts, and other methods are sometimes recommended, such as
      vascularized bone grafts or bone transport using the Ilizarov external fixator.
      The combination of local infection with a massive bone defect exacerbates the
      problem, and provides an even more negative prognosis. The authors treated a
      large bone defect of the forearm with local infection, using a one-bone forearm
      formation with a large vascularized fibula graft. They attached an adequate
      amount of muscle fascia to the vascularized fibula, which was useful not only for
      coverage of the skin defect, but also for treatment of the local infection.
      Twenty months after surgery, elbow and hand functions were maintained, and the
      patient had no disturbance of hand function in daily activities, although
      rotation of the forearm was sacrificed.

PMID- 11336146
TI  - Cross-leg free flap for emergency extremity salvage: case report.
AB  - The use of a cross-leg free flap and consequent limb salvage was successfully
      performed in a 10-year-old boy with a compound open fracture of the tibia,
      involving extensive skin and soft-tissue loss. This method should be kept in
      mind, as it may sometimes, in an emergency situation, lead to lower-extremity
      salvage, as in the case reported.

PMID- 11336147
TI  - Evaluation of blood flow in free microvascular flaps.
AB  - Free flap surgery is routine today, yet little is known of its pathophysiology.
      In this study, the authors evaluated the hemodynamics in different types of free
      microvascular flaps, by measuring intraoperative transit-time flow. Eighty-six
      free transplants--21 free TRAM flaps for breast reconstruction, 18 radial forearm
      flaps for head and neck reconstructions, and 47 muscle flaps for head and neck,
      trunk and lower extremity reconstructions--were studied. Donor artery flow was
      highest in the radial artery (mean: 57.5 +/- 50 (SD) ml/min) but dropped (p <
      0.001) to one tenth (6.1 +/- 2 ml/min) after anastomosis. The flow was lowest
      (4.9 +/- 3 ml/min) in the recipient artery of the TRAM flap but, after
      anastomosis, increased significantly (13.7 +/- 5 ml/min) to the level of the flow
      in the donor artery. The donor-artery flow in muscle flaps had a mean of 15.9 +/-
      11 ml/min, and it significantly increased after anastomosing (23.9 +/- 12
      ml/min). Weight-related intake of blood was highest in the radial forearm flap
      (18.5 +/- 6 ml/ min/100g) and lowest in the TRAM flap (2.5 +/- 1 ml/min/100g).
      The study showed that blood flow through a free microvascular flap does not
      depend on recipient artery flow. Even low-flow arteries can be used as
      recipients, because the flow increases according to free-flap requirements. The
      blood flow through a free microvascular flap depends on the specific tissue
      components of the flap.

PMID- 11336148
TI  - Jean Joseph Emile Letievant: a review of his contributions to surgery and
      rehabilitation.
AB  - The life, education, and contributions of E. Letievant are reviewed. He first
      observed esthesiography, protopathic sensibility, and the "tingling sign" in
      peripheral-nerve lesions toward the end of the 19th century. His thoughts and
      language still remain familiar to us, and his work conveys a poignant freshness.

PMID- 11336149
TI  - Reconstruction of ureteral defects with microvascular vein grafts in a rat model.
AB  - This study was undertaken to test the performance of an autologous vein graft as
      a ureteral replacement in the rat model. Twenty-six rats were divided into three
      groups. In Group 1 (n = 10), the animals had a 3-mm segment of the ipsilateral
      ureter excised and the ureteral defect repaired, using a superficial epigastric
      vein graft. In Group 2 (n = 10), the same ureteral defect was created and again
      repaired, using a superficial epigastric vein graft, with the addition of a
      Silastic stent. The control, Group 3 (n = 6), had the ureter transected and
      repaired solely by means of primary anastomosis. Animals from each group
      underwent urography and were sacrificed for histology at three different
      postoperative intervals: 1, 4, and 12 weeks. Postoperative urography results
      showed normal renal function in the animals with ureteral reconstruction using
      vein grafting aided by a stent, as well as in those with primary ureteral
      anastomosis. No renal function return was seen in the animals with ureteral
      reconstruction by vein grafting alone, without stent support. Histologically, a
      progressive loss of the vascular endothelium, and replacement with the urothelium
      typical of the ureter, was seen in the stented vein grafts. Severe ureteral
      obstruction at the proximal site of the graft and hydronephrosis were seen in the
      vein-graft group without stenting. This study demonstrates that autologous vein
      grafts can be used successfully to correct a ureteral deficit, contingent on
      accurate microsurgical technique and immediate stenting.

PMID- 11336150
TI  - Rat-strain differences in recovery following peripheral-nerve
      allotransplantation.
AB  - The rat model is commonly utilized in peripheral nerve research. Due to the short
      length of the rat limb and the animal's inherent neuroregenerative capacity, the
      timing of assessment of nerve regeneration is critical, and significant
      differences between groups can be lost if assessment is done too late.
      Additionally, the comparison of data from different rat-strain combinations has
      been questioned. This study better defines the time course of recovery after
      peripheral nerve grafting, and examines differences between Buffalo (BUF), Lewis
      (LEW), and ACI rats. Tibial-nerve isografts and allografts were performed and
      harvested at 6, 8, 10, or 14 weeks. Histomorphometry documented a statistically
      significant difference in the ACI/LEW and LEW/LEW combination at 10 weeks. No
      strain differences in graft rejection were noted. The optimal time to assess for
      histomorphometric differences in the ACI/LEW and LEW/LEW combination is at 10
      weeks postoperatively.

PMID- 11336151
TI  - 2-octylcyanoacrylate-assisted microvascular anastomosis: comparison with a
      conventional suture technique in rat femoral arteries.
AB  - Standard microvascular anastomosis using only sutures is a well-established and
      successful technique; however, it is time-consuming and may cause vessel
      narrowing, needle trauma, and tissue reaction. The authors' hypothesis was that 2
      octylcyanoacrylate could simplify microvascular anastomosis and reduce wall
      trauma and reaction. End-to-end anastomoses of the femoral arteries were
      performed in 20 adult rats. Each animal served as its own control. The time taken
      for each anastomosis (from first stitch to release of clamps) was noted, and the
      patency assessed. At day 7, the anastomoses were reassessed for patency, and the
      vessels evaluated histologically. 2-octylcyanoacrylate reduced the need to insert
      more sutures. Anastomotic time in the study group was statistically significantly
      shorter (p < 0.001), and the patency rate was 90 percent, compared to 85 percent
      with the standard suture technique. There was also less intense inflammatory
      reaction, with fewer foreign-body granulomata. This is the first report on the
      use of 2-octylcyanocrylate, currently approved for cutaneous use, for vessel
      anastomosis. Further work on the biomechanics and long-term histologic effects
      will be carried out. 2-octylcyanoacrylate has the potential for simplifying and
      improving the patency rates of arterial microanastomosis.

PMID- 11336152
TI  - Viability of ischemia/reperfused bone determined at the gene expression level.
AB  - Rat bone viability was evaluated, using a bone viability index (BVI) that
      reflects mRNA degradation. To evaluate ischemic injury of the bone, 28 amputated
      hind limbs of Fischer rats (ischemic insult group: four subgroups, each
      containing seven limbs) were preserved at normothermia for 1, 3, 6 and 9 hr and
      the tibiae were harvested. To investigate ischemia/reperfusion injury, another 42
      amputated limbs were transplanted to recipient Fischer rats after ischemia at
      normothermia for 1, 3 and 6 hr, respectively. The tibiae from the transplanted
      limbs were harvested on day 3 and day 7 after the transplantation
      (ischemia/reperfusion group). Seven fresh tibiae were also harvested and used as
      controls (control group). The total RNA isolated from the tibia of each group was
      fractionated by electrophoresis and hybridized with 32P-labelled cDNA of
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and the radioactivity of intact
      and degraded GAPDH mRNA was measured. BVI was calculated as follows: BVI = [A/(A
      + B)] x 100, where A and B represent the radioactivities corresponding to the
      intact GAPDH and degraded GAPDH mRNA band, respectively. In the 1-hr and 3-hr
      ischemia groups, the BVIs of the ischemia/reperfused group were comparable to
      those of controls, although the indexes of the ischemic insult group were
      significantly lower than controls. However, in the 6-hr ischemia group, indexes
      of both the ischemic insult and ischemia/reperfusion groups were significantly
      lower than controls. These results demonstrated that bone damage was detected
      with ischemia at normothermia even after 1 hr; however, this tissue damage was
      overcome by reperfusion. There was no recovery from damage in bones that had been
      preserved for more than 6 hr, resulting in irreversible degeneration. Therefore,
      in clinical vascularized bone grafts, it appears that transplantation should be
      done within a 3-hr ischemic period for it to be successful.

PMID- 11336153
TI  - Microsurgical flap models in the rat.
AB  - Microsurgical flaps have been widely used in clinical reconstructive surgery.
      Although these procedures have achieved great clinical success, utilization of
      microsurgical flap techniques have also led to a number of basic questions that
      researchers must now attempt to answer. The rat has been the source of many flap
      models in these investigations. This article provides a condensed description of
      the procedures, anatomic data, and research applications for skin, muscle,
      myocutaneous, bone, osteomuscular, and osteomyocutaneous microsurgical flap
      models in the rat.

PMID- 11336154
TI  - Update in the pharmacological management of peptic ulcer haemorrhage.
AB  - The management of peptic ulcer haemorrhage still poses questions and
      controversies and this applies to the pharmacological mode. This review suggests
      that high-dose acid suppression is beneficial in reducing rebleeding and surgery
      rates. The choice of acid suppressant is far from conclusive, but emerging
      evidence suggests that proton pump inhibitors may be more effective than H2
      antagonists. The only other drug which may be useful in selected patients is
      octreotide, but its universal use cannot be recommended.

PMID- 11336155
TI  - The effect of jejunal meal feeding on gastroesophageal reflux.
AB  - BACKGROUND: Postprandial gastric distention is frequently associated with
      transient lower esophageal sphincter relaxation and gastroesophageal reflux
      (GER). Since the role of nutrient perfusion into the jejunum in inducing GER is
      not well understood, we studied the effect of jejunal feeding on GER through a
      percutaneous gastrojejunal tube in patients with and without reflux esophagitis.
      METHODS: Nine stroke patients with reflux esophagitis were fed through a
      percutaneous gastrojejunal tube with either a liquid meal (2 kcal/2 ml/min) or
      saline for 2 h randomly on 2 separate days. An esophageal pH probe was placed 5
      cm above the gastroesophageal junction to detect acid reflux. Six stroke patients
      without esophagitis were enrolled as controls. RESULTS: In both the patients with
      esophagitis and the controls, esophageal acid exposure (15.3% (4.9%-28.2%) versus
      2.7% (0.0%-10.8%), P=0.003; 5.9% (0.5%-6.7%) versus 0.0% (0.0%-1.5%), P = 0.01)
      and events of acid reflux (5 (1-16) versus 2 (0-8), P = 0.02; 12 (3-17) versus 1
      (0-4), P = 0.02) were significantly greater during jejunal meal feeding than
      during saline infusion. Furthermore, in the reflux patients, but not in the
      controls, acid clearance time was also greater during jejunal meal feeding than
      during saline infusion (2.9 min (0.5-9.6 min) versus 0.7 min (0.0-4.3 min), P =
      0.04). CONCLUSIONS: We therefore conclude that jejunal nutrient infusion without
      gastric distention can induce GER in both patients with reflux esophagitis and
      controls. This implies that GER induced by jejununal nutrients may in part
      explain the incapability of jejunal tube feeding to prevent gastropulmonary
      aspiration in patients at risk.

PMID- 11336156
TI  - Intragastric nitric oxide/nitrite in Helicobacter pylori-infected subjects.
AB  - BACKGROUND: Nitrite (NO2-) in swallowed saliva is reduced to nitric oxide (NO)
      and other nitrogen oxides by the intragastric acidity. This mechanism is probably
      important for the intragastric clearance of ingested micro-organisms and
      nitrosating compounds. The study examines the balance between intragastric NO and
      NO2- in relation to endogenous acid production and infection with Helicobacter
      pylori. METHODS: Six healthy H. pylori-negative and six H. pylori-positive
      volunteers with no known gastroduodenal pathology were examined after an
      overnight fast. Gastric NO was measured using a chemiluminescence technique and
      pH as well as NO2- were analysed in gastric aspirates. RESULTS: Gastric NO was
      slightly lower in H. pylori-positive subjects (1560 +/- 211 ppb) than in
      uninfected controls (2112 +/- 430 ppb; P > 0.05) during basal conditions, whereas
      both pH and NO2- concentration were similar in the two groups. During inhibition
      of acid secretion (omeprazole 20 mg b.i.d. over 5 days) median pH and mean NO2-
      concentration in gastric aspirates were significantly higher in H. pylori
      positives than in the controls. Furthermore, during omeprazole treatment the
      intragastric NO levels were almost absent in H. pylori positives, whereas
      approximately 50% remained in H. pylori-negative individuals. CONCLUSION: Proton
      pump inhibition in H. pylori-infected individuals abolishes the intragastric
      chemical reduction of swallowed NO2- in the fasting stomach.

PMID- 11336157
TI  - Functional dyspepsia is associated with cagA-positive Helicobacter pylori
      strains.
AB  - BACKGROUND: The antigen CagA can be used as a marker for virulence of
      Helicobacter pylori. It is tempting to assume that H. pylori strains positive for
      cytotoxin-associated gene A (cagA) could be responsible for functional dyspepsia.
      A cross-sectional study was performed in patients presenting with functional
      dyspepsia to correlate the clinical presentation with the presence of cagA
      positive and -negative H. pylori strains. METHODS: Consecutive patients referred
      for endoscopy were studied. An inclusion criterion was the absence of any
      endoscopic abnormality. Biopsy specimens were obtained from the gastric antrum
      for HE and immunoperoxidase stain, rapid urease test, and culture. A serum sample
      was taken for detection of IgG antibodies against H. pylori as well as CagA. A
      validated questionnaire of 14 questions regarding the upper gastrointestinal
      tract was used for assessment of the clinical presentation. Nine questions were
      scored on a 5-point Likert scale. RESULTS: 422 patients were included, 222 were
      H. pylori-positive, the remaining 200 were H. pylori-negative. Mean symptom score
      in patients with cagA-positive strains was significantly higher than in patients
      with cagA-negative strains. No difference was present if cagA-negative patients
      were compared with H. pylori-negative dyspeptics. Four different complaints were
      more prevalent in the cagA-positive patients compared with cagA-negatives. When
      cagA-positive patients were compared with H. pylori-negative dyspeptics, seven
      complaints were significantly more prevalent in cagA-positives; when cagA
      negatives were compared this number was only two. CONCLUSIONS: Functional
      dyspeptics with cagA-positive H. pylori strains have more dyspeptic symptoms and
      higher symptom scores than patients with cagA-negative H. pylori strains as well
      as H. pylori-negative functional dyspeptics.

PMID- 11336158
TI  - Transforming growth factor-alpha delays gastric emptying and small intestinal
      transit in suckling rats.
AB  - Transforming growth factor-alpha (TGF-alpha) is a biologically potent polypeptide
      detected in the gastrointestinal tract in suckling rats. The major goal of the
      present study was to test the hypothesis that the administration of TGF-alpha
      affects gastric emptying and small intestinal transit in suckling rats. Suckling
      (12-day-old) rats fasted 16 h received rat TGF-alpha subcutaneously (s.c.) or
      orogastrically in varying doses (0, 0.5, 1.0 microg/rat in 0.1% BSA). Control
      animals received 0.1% BSA only. Poly R-478 dye was used as a motility marker.
      Rats were decapitated 45 min after marker administration and the amount of dye in
      the stomach and the small intestine was measured by spectrophotometry.
      Subcutaneous administration of TGF-alpha significantly delayed stomach
      evacuation. In controls, the stomach contained 21.4 +/- 1.4% (mean +/- s(x)) of
      the Poly R-478 marker, whereas in TGF-alpha treated rats the stomach contained
      37.2 +/- 2.8% of the total Poly R-478 dye given to animals. The delaying effect
      of TGF-alpha was time- and dose-dependent. Small intestinal transit was also
      significantly delayed. The proximal jejunum of TGF-alpha treated rats contained a
      1.4-fold higher amount of marker in comparison with control rats. Orogastrically
      administered rTGF-alpha did not affect gastric emptying or intestinal transit. In
      conclusion, s.c. administration of rat TGF-alpha significantly delayed the
      gastrointestinal motility in vivo in suckling rats.

PMID- 11336159
TI  - Role of cholecystokinin in relaxation of the proximal stomach.
AB  - Ingestion of a meal causes proximal gastric relaxation (accommodation). The
      magnitude of accommodation is related to the fat content of the meal. A role for
      cholecystokinin (CCK) has been suggested. However, under fasting conditions
      intravenous CCK to postprandial levels does not induce a similar accommodation.
      This study further explores the role of CCK in accommodation. A gastric barostat
      was used in eight healthy persons to study accommodation in response to a
      carbohydrate meal with intravenous CCK (CH-CCK), carbohydrate meal with
      intravenous placebo (CH-placebo) and a fat rich meal with intravenous placebo
      (FAT). VAS scores for satiety and plasma CCK levels were obtained. In the first
      postprandial hour the FAT meal induced a relaxation of 112 +/- 29 ml, the CH-CCK
      meal 49 +/- 36 ml and the CH-placebo meal 12 +/- 32 ml (FAT versus CH-placebo P =
      0.03; FAT versus CH-CCK P = 0.09). In the second postprandial hour, intragastric
      bag volume returned to baseline with all meals. The FAT meal had the most
      pronounced effect with respect to satiety, CH-placebo the least. In the first
      postprandial hour, plasma CCK levels increased with the CH-CCK and FAT meals but
      not with the CH-placebo meal; in the second postprandial hour, levels remained
      elevated with the CH-CCK meal. It is concluded that a carbohydrate meal with
      exogenous CCK does not induce fundic relaxation, whereas a fat-rich meal
      (endogenous CCK) does, despite similar plasma CCK levels.

PMID- 11336160
TI  - Fructose malabsorption is associated with decreased plasma tryptophan.
AB  - BACKGROUND: Fructose malabsorption is characterized by the inability to absorb
      fructose efficiently. As a consequence fructose reaches the colon where it is
      broken down by bacteria to short fatty acids, CO2, H2, CH4 and lactic acid.
      Bloating, cramps, osmotic diarrhea and other symptoms of irritable bowel syndrome
      are the consequence and can be seen in about 50% of fructose malabsorbers.
      Recently it was found that fructose malabsorption was associated with early signs
      of depressive disorders. Therefore, it was investigated whether fructose
      malabsorption is associated with abnormal tryptophan metabolism. METHODS: Fifty
      adults (16 men, 34 women) with gastrointestinal discomfort were analyzed by
      measuring breath hydrogen concentrations after an oral dose of 50 g fructose
      after an overnight fast. They were classified as normals or fructose malabsorbers
      according to their breath H2 concentrations. All patients filled out a Beck
      depression inventory questionnaire. Blood samples were taken for plasma
      tryptophan and kynurenine measurements. RESULTS: Fructose malabsorption (breath
      deltaH2 production >20 ppm) was detected in 35 of 50 individuals (70%). Subjects
      with fructose malabsorption showed significantly lower plasma tryptophan
      concentrations and significantly higher scores in the Beck depression inventory
      compared to those with normal fructose absorption. CONCLUSIONS: Fructose
      malabsorption is associated with lower tryptophan levels that may play a role in
      the development of depressive disorders. High intestinal fructose concentration
      seems to interfere with L-tryptophan metabolism, and it may reduce availability
      of tryptophan for the biosynthesis of serotonin (5-hydroxytryptamine). Fructose
      malabsorption should be considered in patients with symptoms of depression and
      disturbances of tryptophan metabolism.

PMID- 11336161
TI  - Candidate gene region 15q26 and genetic susceptibility to coeliac disease in
      Finnish families.
AB  - BACKGROUND: Studies in the Irish and British populations have indicated that
      chromosome region 15q26 could include a novel non-HLA-linked locus conferring
      genetic susceptibility to coeliac disease. The locus is of particular interest,
      since a type I diabetes risk locus, IDDM3, maps to the same position. It was
      tested whether this locus shows evidence for genetic linkage to coeliac disease
      in Finland. METHODS: Ninety-nine Finnish families with at least one affected
      sibpair were studied. Five microsatellite markers mapped within approximately 20
      cM region on chromosome 15q26 were typed. Non-parametric linkage (NPL) scores and
      allelic transmission (TDT) were studied. RESULTS: No evidence for genetic linkage
      could be obtained by the NPL scores calculated by the Genehunter program.
      However, transmission/disequilibrium analysis (TDT) revealed that haplotype
      D15S107*1-D15S120*6 was statistically significantly more frequently transmitted
      to affected than expected by chance (TDT chi2 9.0; P = 0.003). The subgroup of
      families having this haplotype, however, did not differ from the others,
      regarding to disease manifestation, HLA status, or geographical origin.
      CONCLUSION: The 15q26 region appears not to be a major non-HLA susceptibility
      locus for gluten sensitivity in Finland, but a particular haplotype which may
      harbour a susceptibility gene was identified.

PMID- 11336162
TI  - Impaired health-related quality of life in inflammatory bowel diseases:
      psychosocial impact and coping styles in a national German sample.
AB  - BACKGROUND: The purpose of this study is to give a detailed survey of the disease
      specific and generic quality of life (HRQOL) of adult patients suffering from
      inflammatory bowel disease (IBD) in Germany. METHODS: 1322 patients suffering
      from IBD were examined in a cross-sectional study. A questionnaire assessing
      disease-specific and generic quality of life, coping, and hopelessness was sent
      to members of the German Crohn/Colitis association. RESULTS: Compared to the
      general population, the generic HRQOL in IBD patients is significantly reduced.
      Active coping has a negative influence on patients' generic physical HRQOL during
      an active phase (beta = -0.31), while this association is not present in the case
      of patients in remission (beta = -0.02, interaction: P = 0.0003). Depressive
      coping is strongly and negatively associated with assessment of the physical
      (beta = -0.39, P < 0.0001) and mental (beta = -0.66, P < 0.0001) HRQOL. Disease
      specific burdens are mainly reported in the physical dimension. CONCLUSION: The
      pattern of psychosocial impact of disease in German IBD patients is largely
      congruent with the one observed in the USA and Canada, but shows some specific
      differences. The a priori unexpected finding that active coping was associated
      with poor HRQOL in active IBD status illustrates the importance of considering
      different determinants of HRQOL in terms of their mutual interaction.

PMID- 11336163
TI  - Does adjuvant nutritional support diminish steroid dependency in Crohn disease?
AB  - BACKGROUND: Nutritional therapy plays an important role in the management of
      Crohn disease, particularly during the acute phase. Nutritional supplementation
      may also prevent relapses during the quiescent phase of Crohn disease, though
      this aspect has not been widely explored. METHODS: Thirty-three patients with
      Crohn disease in remission were studied. All had steroid-dependent disease.
      Patients were randomized to receive either elemental diet (n = 19, EO28 Extra) or
      polymeric diet (Forticips, n = 14). The supplement was given orally in addition
      to normal food in an amount to provide 35%-50% of pre-trial total calorie intake.
      Prednisolone was withdrawn gradually. Patients were followed up for 12 months.
      Failure was defined as increase in CDAI by 100 points from baseline to >200,
      inability to withdraw chronic steroid therapy completely, need for surgery or
      steroid therapy. RESULTS: The nutritional supplement was successful in 14 (43%)
      patients who remained in remission for 12 months with complete withdrawal of
      steroids. The response to elemental diet (42%) was similar to that of polymeric
      diet (43%). Nutrition supplement failed in 13 (39%). Six (18%) patients were
      intolerant to enteral feeding because of smell and taste problems. Per-protocol
      analysis of data indicated that the success rate of nutrition supplement in
      steroid-dependent patients was 52% (14 out of 27 patients). No disease or patient
      related factors helped predict the response to nutrition supplement. CONCLUSION:
      Nutritional supplementation with either an elemental or polymeric diet may
      provide a safe and effective alternative to chronic steroid therapy in patients
      with steroid-dependent Crohn disease.

PMID- 11336164
TI  - Differential activation of cytokine secretion in primary human colonic
      fibroblast/myofibroblast cultures.
AB  - BACKGROUND: Fibroblasts and myofibroblasts are known to secrete a wide spectrum
      of cytokines, but the individual spectrum is tissue-specific. We investigated the
      effect of cell activation on cytokine secretion of isolated human colonic
      fibroblasts/myofibroblasts from control patients and patients with mucosal
      inflammation. METHODS: Primary cultures of human colonic submucosal
      fibroblasts/myofibroblasts were incubated with IL-1alpha (100 U/ml), IL-Ibeta (10
      ng/ml), IL-10 (10 ng/ml), TNF (10 ng/ml), PMA (10 ng/ml), LPS (50 ng/ml), IL-4
      (10 ng/ml), or a combination of IL-1 and TNF. Secreted cytokines were determined
      by ELISA. NF-kappaB activation was demonstrated by electrophoretic mobility-shift
      assays (EMSA). RESULTS: Incubation of colonic fibroblasts/myofibroblasts with IL
      1, LPS, TNF and PMA induced secretion of IL-6, IL-8, M-CSF and GM-CSF. IL-8 and
      IL-6 secretion could be stimulated by IL-1alpha, IL-1beta, TNF, PMA and LPS
      within 6 h of incubation. IL-6 secretion was stimulated from 0.5 +/- 0.01 pg/h x
      microg fibroblast protein to 18.5 +/- 2.6 pg/h x microg fibroblast protein with
      IL-1beta (P < 0.01). IL-8 secretion was stimulated from 1.0 +/- 0.1 pg/h x microg
      fibroblast protein to 41.1 +/- 3.6 pg/h x microg (P < 0.005). IL-4 and IL-10 did
      not change cytokine secretion significantly. No significant differences between
      cultures from normal and inflamed mucosa were observed. TNF and IL-1 induced NF
      kappaB activation. ALLN, a proteasome and NF-kappaB activation inhibitor, reduced
      TNF-mediated IL-8, GM-CSF and M-CSF induction significantly, whereas induction of
      IL-6 secretion remained unchanged. CONCLUSION: Human colonic myofibroblasts can
      secrete large amounts of IL-6, IL-8, M-CSF and GM-CSF upon stimulation. The
      induction of IL-8, M-CSF and GM-CSF, but not of IL-6 secretion, is mediated
      mainly by NF-kappaB activation. The cytokine profile and the total amounts of
      cytokines released suggest that colonic myofibroblasts can play a role in
      leukocyte recruitment and during mucosal inflammation. They therefore have to be
      regarded as an important part of the mucosal immune system.

PMID- 11336165
TI  - Biological implications of circulating soluble intercellular adhesion molecule-1
      in colorectal cancer patients.
AB  - BACKGROUND: Intercellular adhesion molecule-1 (ICAM-1) is assumed to play a role
      in cell-cell and cell-extracellular matrix interactions. We evaluated the
      relationship between local expression of ICAM-1 and the circulating level of
      sICAM-1, and clarified its biological implications. METHODS: Serum concentrations
      of sICAM-1 in 94 colorectal cancer patients were determined. Tissue
      concentrations of sICAM-1 in the tumor, colorectal adenoma, and the normal mucosa
      were also determined. The expression of ICAM-1 in the tumor was evaluated
      immunohistochemically. RESULTS: The serum concentration of sICAM-1 in the
      patients was significantly higher than that in the controls, and the tumor size
      was the independent pathological factor that was associated with the serum ICAM-1
      level. ICAM-1 immunoreactivity was seen intensively in the stromal cells in the
      tumor. The tissue concentration of sICAM-1 in the normal mucosa was significantly
      lower than that in the adenoma and the early carcinoma. The tissue concentration
      of sICAM-1 in the advanced carcinoma significantly decreased in association with
      the increase in tumor size. This fluctuation of ICAM-1 expression in the tumor
      was also associated with the metastatic potential even at an early stage of the
      disease. CONCLUSIONS: The tissue concentration of sICAM-1 increased during
      tumorigenesis and at an early stage of carcinoma, and decreased in association
      with progression of the disease. Serum sICAM-1 level reflected the fluctuation of
      ICAM-1 expression in the tumor. Evaluation of serum concentration of sICAM-1 may
      be associated with tumor load and can reflect disease progression in colorectal
      cancer patients.

PMID- 11336166
TI  - Allelic loss of chromosome 2p21-16.3 is associated with reduced survival in
      sporadic colorectal cancer.
AB  - BACKGROUND: Since allelic loss of genes involved in the development of colorectal
      cancer could serve as prognostic markers, we examined the correlation between
      loss of markers linked to the hMSH2/hMSH6 (2p21-16.3), hMLH1 (3p21.3), APC (5q21
      22), p53 (17p13.1) and DCC (18q21.3) loci and survival in a series of 64
      consecutively collected colorectal cancers. METHODS: The association between
      allelic loss and survival was analysed by univariate and multivariate tests to
      identify independent variables of survival. RESULTS: Loss of chromosome 2p21-16.3
      reduced the overall 5-year survival from 52% to 15% (P = 0.0003). The prognostic
      significance was evident in patients with Dukes' A + B as well as Dukes' C
      tumours. A multivariate analysis comparing Dukes' staging, age at diagnosis,
      tumour localization, sex, loss of chromosome 2p21-16.3, 3p21.3, 5q21-22, 17p13.1
      or 18q21.3 and microsatellite instability showed that only Dukes' staging (hazard
      ratio 3.0; 1.4-6.5 with 95% confidence interval, P = 0.0065) and loss of 2p21
      16.3 (hazard ratio 6.2; 2.3-16.8 with 95% confidence interval, P = 0.0006) were
      independent variables of survival. Loss of 2p21-16.3 was, moreover, associated
      with increased loss of the other tumour suppressor loci (P = 0.012). CONCLUSIONS:
      The results show that loss of 2p21-16.3 is an independent indicator of survival
      in patients with colorectal cancer.

PMID- 11336167
TI  - Kinetics of urinary trypsin inhibitor in patients undergoing partial hepatectomy.
AB  - BACKGROUND: The kinetics and role of urinary trypsin inhibitor (UTI) in liver
      surgery are unclear. We investigated the effects of preoperative liver function
      and the extent of liver resection on postoperative UTI synthesis in the liver
      after partial hepatectomy. METHODS: Sixty-one consecutive patients who underwent
      liver resection were the subjects of the study. Plasma and urine UTI, plasma C
      reactive protein (CRP) and plasma and urine creatinine were measured
      perioperatively. RESULTS: Although the average plasma UTI level did not change
      significantly, the average urine UTI level per day showed a change similar to
      that of the average plasma CRP level, reaching a maximum of approximately eight
      times the preoperative level on the second postoperative day (86,610 +/- 53,109
      U/day). The maximum postoperative increase in urine UTI excretion per day (delta
      uUTImax) correlated significantly with the maximum increase in CRP and the
      increase in creatinine clearance. Multiple regression analysis revealed that
      delta-uUTImax was significantly and positively correlated with the indocyanine
      green plasma disappearance rate and operation duration, and negatively correlated
      with the resection rate. CONCLUSIONS: The postoperative urine UTI level may
      reflect preoperative liver function and the extent of liver resection after
      partial hepatectomy.

PMID- 11336168
TI  - Orthotopic liver transplantation for idiopathic portal hypertension: indications
      and outcome.
AB  - BACKGROUND: Idiopathic portal hypertension is a rare clinical syndrome which may
      be associated with a spectrum of histological lesions, including nodular
      regenerative hyperplasia and incomplete septal cirrhosis. Here, we report eight
      adult patients with idiopathic portal hypertension who experienced an unusually
      severe clinical evolution characterized by the development of progressive hepatic
      failure requiring orthotopic liver transplantation. Our aims are: (a) to stress
      the distinctive clinical presentation of these patients, (b) to describe their
      biological and histopathological features, and (c) to evaluate the results of
      orthotopic liver transplantation in this rare indication. METHODS: Complete
      clinical charts and histological data were available in all patients. All
      patients were male. Their age at diagnosis ranged from 17 to 59 years.
      Complications of portal hypertension revealed the disease in all cases. Medical
      treatment was performed in all patients and portosystemic shunt in three.
      RESULTS: The development of progressive hepatic failure led to the indication of
      liver transplantation after a delay ranging from 3 to 10 years. Explanted livers
      showed pure nodular regenerative hyperplasia in three patients and incomplete
      septal cirrhosis in five. Recovery was uneventful. All patients are alive,
      without recurrence of the disease. CONCLUSIONS: This report points to the
      existence of severe cases of idiopathic portal hypertension occurring without
      underlying or associated systemic disease and characterized by a poor clinical
      course and requiring liver transplantation.

PMID- 11336169
TI  - Ammonia and endogenous benzodiazepine-like compounds in the pathogenesis of
      hepatic encephalopathy.
AB  - BACKGROUND: Ammonia and endogenous benzodiazepines (BDZs) are two of the most
      important agents among those taken into consideration in the pathogenesis of
      hepatic encephalopathy (HE). METHODS: Venous ammonia and endogenous BDZs sera
      levels were assayed in 58 liver cirrhosis patients (34 male, 24 female) free of
      commercial BDZs. Endogenous BDZs were measured by binding assay after high
      performance liquid chromatography purification. Ammonia was assessed by
      colorimetric test. RESULTS: Endogenous BDZs and ammonia were significantly higher
      in Child-Pugh class C than in class B and class A (P < 0.05), correlating to the
      severity of the liver dysfunction but not with the degree of HE. A significant
      difference, in fact, was noted between degree 0 (no HE) versus III-IV of HE (P <
      0.05), but not between degrees I-II versus III-IV. Regression analysis performed
      to find a correlation between the ammonia and BDZ levels in HE resulted negative.
      CONCLUSION: Clinical evidence is provided in cirrhotic patients that ammonia and
      endogenous BDZ levels do not correlate with each other in the outcome of HE.

PMID- 11336170
TI  - Hepatitis C and the leptin system: bound leptin levels are elevated in patients
      with hepatitis C and decrease during antiviral therapy.
AB  - BACKGROUND: Serum leptin levels are elevated in alcoholic liver cirrhosis and
      thus might be involved in the anorexia and hypermetabolism often seen in those
      patients. We hypothesized that the leptin system is modulated in patients with
      hepatitis C and might be affected by antiviral therapy. The aim of this study was
      to investigate the different leptin components in serum of patients with
      hepatitis C before, during and after interferon alpha and ribavirin therapy and
      in controls. METHODS: 25 patients (11 female, 14 male) with chronic hepatitis C
      were compared with body mass index, gender and age-matched controls (n = 25).
      Patients were treated with interferon alpha alone (3 MU tiw) or in combination
      with ribavirin for 6-12 months. Free leptin and bound leptin levels were measured
      using specific radioimmunoassays before interferon therapy, at 12 weeks of
      therapy and after 3 months of follow-up. RESULTS: Free leptin levels were higher
      in female than in male subjects, both for patients (P < 0.01) and controls (P <
      0.05). Bound leptin levels were elevated in both female (P < 0.05) and male (P <
      0.001) patients compared to controls. No alteration of free leptin levels was
      found during therapy, whereas bound leptin levels decreased after 3 months of
      therapy (P < 0.005) and re-increased to the baseline levels 3 months after
      therapy was stopped. Responder but not non-responder had decreased bound leptin
      levels (P < 0.01) comparing pre- and posttreatment levels. However, no
      significant correlations were determined between any of the leptin components to
      virus load, ALT, TNF alpha receptor levels (sTNFR-75, sTNFR-55) and
      histopathology at any time point. CONCLUSION: Since no correlation was found
      between the different leptin components and any of the inflammatory markers, the
      decrease in bound leptin levels during antiviral therapy suggests either a direct
      interferon-dependent effect on the leptin system or an alteration of other leptin
      secretagogues.

PMID- 11336171
TI  - Do we need a computed tomography examination in all patients with acute
      pancreatitis within 72 h after admission to hospital for the detection of
      pancreatic necrosis?
AB  - BACKGROUND: The aim of this prospective study was to define the role of an
      initial contrast-enhanced computed tomography (CT) obtained within 72 h after
      admission to hospital for determining the prognosis of acute pancreatitis and to
      investigate whether CT scans can be replaced by conventional prognostic
      parameters. METHODS: The study involves 231 patients admitted to the Luneburg
      clinic with a first attack of acute pancreatitis from 1988 to 1995. In all of
      them, a contrast-enhanced CT was performed within 72 h of admission and scored
      according to Balthazar. The results were compared with the Ranson and Imrie
      laboratory prognostic scores and with parameters of the severity of the disease:
      the initial organ failure according to the Atlanta classification; days spent on
      intensive care unit or altogether in hospital; indication for artificial
      ventilation, dialysis and surgical intervention (necrosectomy); development of
      pancreatic pseudocysts; and mortality. RESULTS: Although there was a good
      statistical correlation between Ranson, Imrie, and Balthazar scores with the
      severity of the disease (P < 0.001 to P = 0.03), low and moderately raised Ranson
      (0-2, 0-5 points) and Imrie scores (0-1.0-3 points) failed to identify all
      patients with pancreatic necrosis with sufficient sensitivity rates (31.7; 78.0
      and 39.0; 78.0%), positive (32.6; 25.3 and 75.0; 45.0%) and negative (91.0; 87.9
      and 85.4; 84.8%) predictive values. CONCLUSIONS: A contrast-enhanced CT on
      admission correlates significantly with the severity of the disease and cannot be
      replaced by conventional laboratory prognostic scores. The decision to use a CT
      cannot depend on the results of the Ranson/Imrie scores.

PMID- 11336172
TI  - How useful is selection based on alarm symptoms in requesting gastroscopy? An
      evaluation of diagnostic determinants for gastro-oesophageal malignancy.
AB  - OBJECTIVE: To derive and evaluate diagnostic determinants of gastro-oesophageal
      malignancy as a means of helping family physicians select patients for 'open
      access' gastroscopy. In this multicenter study, 861 consecutive patients were
      investigated with first-time gastroscopy (study population). Another 1153
      patients were studied during the next 6 years (validation population). General
      practitioners registered symptoms relevant to malignancy and patient histories;
      the results of gastroscopies were received from the endoscopists. METHODS:
      Univariate and multivariate analyses resulted in four relevant symptoms that were
      then compared with 'alarm symptoms' previously published in the literature.
      Receiver-operating characteristic analysis was used to evaluate the probability
      of finding malignancy using these two sets of symptoms. RESULTS: Positive answers
      regarding the symptoms, weight loss and dysphagia, together with negative answers
      on pain during the night and heartburn, predicted malignancy in the study
      population with an AUC (area under the curve) of 0.90. 'Alarm symptoms' performed
      less well in the study population (AUC 0.85), although reproducibility was better
      in the validation population (0.71 versus 0.63). If exclusion of malignancy had
      been chosen as the only valid reason for requesting gastroscopy, then pre
      selection with the help of these symptoms would have reduced the number of
      requests by 10%. CONCLUSION: Thorough evaluation of 'classical' alarm symptoms in
      dyspeptic patients might help minimize unnecessary gastroscopy requests by GPs
      seeking a safe treatment decision.

PMID- 11336173
TI  - Common bile duct obstruction due to candidiasis.
AB  - Biliary obstruction with its wide range of potential causes (e.g. neoplastic
      lesions, gallstones and inflammatory processes) is a common disease in
      gastroenterology. Although infections with Candida and other fungal species have
      increasingly been recognized in patients with certain predispositions, fungal
      involvement of the biliary tract is extremely rare. We report the case of a male
      patient with a past history of long-time mechanical ventilation and who was
      referred to our department with cholangitis. Endoscopic retrograde cholangio
      pancreatography (ERCP) of the septic patient revealed a high-degree stenosis of
      the distal common bile duct with a prestenotic dilation which was strongly
      suspicious of an underlying malignancy. Control ERCP revealed a beads-like
      deformation of the intra- and extrahepatic bile duct system which was compatible
      with chronic secondary sclerosing cholangitis. Examining the bile duct system
      with a balloon catheter, a long tubular. filamentous structure with several
      branches at its sides could be extracted and was assessed histologically to be a
      Candida conglomerate. Candida colonization of the bile duct was confirmed by
      microbiological analysis of aspirated bile.

PMID- 11336174
TI  - Elevated plasma (1-->3)-beta-D-glucan, a fungal cell wall constituent, in a
      subgroup of Crohn disease.

PMID- 11336175
TI  - Laragh's lessons in pathophysiology and clinical pearls for treating
      hypertension.

PMID- 11336176
TI  - Differential salt-sensitivity in the pathogenesis of renal damage in SHR and
      stroke prone SHR.
AB  - The spontaneously hypertensive rat (SHR) and the stroke prone SHR (SHRsp) display
      contrasting susceptibilities to the development of the severe hypertensive
      lesions of malignant nephrosclerosis, both with aging and after the provision of
      a high salt intake on the background of a Japanese style "stroke prone" rodent
      diet. The SHR is relatively resistant, whereas the SHRsp is markedly susceptible.
      The responsible mechanisms remain controversial. Blood pressure (BP)
      radiotelemetry was used to investigate the interrelationship between salt intake,
      systolic BP, and renal damage in 8- to 12-week-old male SHR and SHRsp given a
      standard North American style diet for 6 weeks, a standard diet plus 1% NaCl as
      drinking water for 6 weeks, or an 8% NaCl diet plus tap water for 4 weeks. After
      4 weeks, BP was significantly greater in the SHRsp compared to the SHR and was
      significantly more sensitive to supplemental salt in the SHRsp than in SHR.
      Average systolic pressures during week 5 (after 4 weeks on standard diet plus tap
      water, standard diet plus 1% NaCl, and 8% NaCl diet plus tap water) were 188.0 +/
      3.0 mm Hg, 207.3 +/- 5.6 mm Hg, and 226 +/- 9.4 mm Hg in SHRsp compared with
      171.4 +/- 3.8 mm Hg, 180.6 +/- 3.8 mm Hg, and 190.3 +/- 5.0 mm Hg in SHR. In the
      absence of supplemental NaCl, both strains exhibited minimal evidence of
      hypertensive renal damage until about 16 weeks of age. A high salt intake
      resulted in the development of lesions of malignant nephrosclerosis (fibrinoid
      necrosis and thrombosis of small vessels and glomeruli) in the SHRsp but not in
      the SHR; semiquantitative histologic renal damage scores in SHRsp versus SHR
      being 10.4 +/- 2.0 versus 0.7 +/- 0.2 after 6 weeks of standard diet plus 1%
      NaCl, and 32.1 +/- 2.5 versus 0.7 +/- 0.4 after 4 weeks of 8% NaCl diet plus tap
      water; P < .001 for both comparisons. The development of more severe hypertension
      in salt-supplemented SHRsp could only partly account for the severity of renal
      damage in SHRsp, the increase in which was disproportionate to the increase in
      absolute BP. However, the rate of increase of BP was greater in the SHRsp and
      this might have contributed to the greater renal damage observed in the SHRsp.
      These data indicate that the contrasting genetic susceptibility to renal damage
      between SHR and SHRsp is mediated, at least in part, by a differential BP salt
      sensitivity.

PMID- 11336177
TI  - Effects of quinapril on expression of eNOS, ACE, and AT1 receptor in
      deoxycorticosterone acetate-salt hypertensive rats.
AB  - Angiotensin II and nitric oxide (NO) may play a role in hypertensive
      cardiovascular remodeling. We evaluated the effects of long-term treatment with
      quinapril, an angiotensin converting enzyme (ACE) inhibitor, on expression of
      endothelial NO synthase (eNOS), ACE, and angiotensin II type 1 (AT1) receptor in
      the left ventricle and evaluated these relations to myocardial remodeling in
      deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Deoxycorticosterone
      acetate-salt rats were induced with weekly injections of DOCA (30 mg/kg) and 1%
      saline in drinking water after right nephrectomy. Quinapril (DOCA-QUI, 10
      mg/kg/day, subdepressor dose) or AT1 receptor antagonist TCV-116 (DOCA-TCV, 5
      mg/kg/day, subdepressor dose) or vehicle (DOCA-V) were given after induction of
      DOCA-salt hypertension for 5 weeks, and age-matched sham-operated rats (ShC)
      served as a control group. The eNOS expression in the left ventricle were
      significantly decreased in DOCA-V compared with ShC, and were significantly
      increased in DOCA-QUI and DOCA-TCV compared with ShC and DOCA-V. The gene
      expression of ACE, AT1 receptor, and type I collagen mRNA were significantly
      increased in DOCA-V compared with ShC, and significantly suppressed in DOCA-QUI
      compared with DOCA-V. The DOCA-V rats demonstrated a significant increase of the
      wall-to-lumen ratio, perivascular fibrosis, and myocardial fibrosis, with all
      these parameters being significantly improved by quinapril. Myocardial remodeling
      in DOCA-salt hypertensive rats was significantly ameliorated by a subdepressor
      dose of quinapril, which may be due to an increase in eNOS mRNA and protein
      expression and a decrease in ACE and AT1 receptor mRNA expression in the left
      ventricle.

PMID- 11336178
TI  - Morphology of renal afferent arterioles and glomeruli, heart weight, and blood
      pressure in primates.
AB  - In a Caribbean outbred population of African green monkeys (Cercopithecus
      aethiops), 5 to 10% of feral adults have elevated blood pressure (BP). We have
      investigated whether the increased pressure is associated with abnormal renal
      afferent arteriole structure or glomerular number. In seven young adult (aged 7
      to 13 years) male monkeys with consistently high BP (mean BP, 111 mm Hg; ketamine
      anesthesia) and seven controls (mean BP, 81 mm Hg), the morphology of the renal
      vasculature has been analyzed in three cortical zones. In each animal, the left
      kidney vasculature was fixed while relaxed and at known intravascular pressure,
      and afferent arteriolar diameter and media cross-sectional area were estimated.
      The right kidney was perfusion-fixed and prepared for unbiased stereologic
      estimation of glomerular number and size. No difference was found in afferent
      arteriole lumen diameter or media cross-sectional area, or in glomerular number
      or size, between the high BP group and controls. There was no difference in heart
      weight between the two groups, but there was a negative correlation between left
      ventricle heart weight and afferent arteriole diameter (controls: r = -0.81, P =
      .025; all animals: r = -0.70, P = .005, slope about 3.5% reduction in lumen
      diameter for 10% increase in heart weight). The results suggest that cardiac mass
      and renal afferent arteriole structure may be controlled by a common mechanism
      unrelated to BP measured in anesthesia. However, the lack of conscious
      measurements prevents conclusions as to whether this mechanism involves
      ambulatory BP.

PMID- 11336179
TI  - Association between albumin:creatinine ratio and 24-hour ambulatory blood
      pressure in essential hypertension.
AB  - Microalbuminuria (MAU) is often found in essential hypertension (EH) and
      represents a sign of renal and cardiovascular damage. In the present study, we
      aimed to look at the association between ambulatory blood pressure (BP) and
      urinary albumin excretion (UAE). We studied 140 patients aged 50.1 +/- 11.6 years
      referred for 24-h ambulatory blood pressure monitoring (ABPM) and, separately, 46
      untreated subjects with newly diagnosed EH. Urinary albumin excretion was
      evaluated by determination of the albumin-to-creatinine ratio (ACR) in the first
      voided morning urine sample taken the same day as the ABPM was started. According
      to the ACR, patients were categorized as having normoalbuminuria (ACR < 1.5
      mg/mmol), borderline MAU (1.5 < or = ACR < 3.0 mg/mmol), and overt MAU (ACR > or
      = 3.0 mg/mmol). Mean ACR was significantly higher in hypertensive than
      normotensive individuals (2.17 +/- 2.67 mg/mmol and 1.72 +/- 2.97 mg/mmol,
      respectively, P = .012). Average 24-h, daytime and nighttime systolic BP and
      diastolic BP were lower in patients with normoalbuminuria than in the other two
      groups and did not differ among the two microalbuminuric groups. Univariate
      regression analysis showed a close relationship between ACR and ambulatory BP.
      Strong correlation between BP and ACR in the normoalbuminuric and borderline
      microalbuminuric range was also obtained in the group of 46 newly diagnosed
      hypertensive patients. In conclusion, the threshold level of ACR > or = 3.0
      mg/mmol currently used to define microalbuminuria may be not applicable to EH.
      Instead, a threshold level of ACR > or = 1. 5 mg/mmol may be more appropriate.

PMID- 11336180
TI  - Rapid adjustment of antihypertensive drugs produces a durable improvement in
      blood pressure.
AB  - Antihypertensive drugs are often initiated and adjusted over a period of weeks to
      months. It is not clear whether the time and inconvenience of this approach is
      necessary. We studied whether or not drug adjustment over several days in the
      context of a physician-nurse team could produce a durable blood pressure benefit
      according to home blood pressure measurements. Sixty-eight patients (aged 65 +/-
      1 years, 47% men) were referred for management of hypertension. Indications for
      referral were new hypertension (13%), known/controlled hypertension (30%), or
      known/uncontrolled hypertension (57%). Patients had one to three brief nurse
      visits/day and were provided with an accurate semiautomated device for self-blood
      pressure (BP) measurement. Sixty patients provided follow-up data. Group 1 (n =
      16) required no change in their preexisting drug regimen during clinic visits,
      whereas group 2 (n = 44) had drug therapy initiated or adjusted over 4 +/- 1
      days. Patients were evaluated at baseline, at dismissal from the clinic, and at
      latest follow-up (mailed-in report of 42 readings taken over 7 days at 1- to 3
      month intervals). Mean follow-up was 11 +/- 0.5 months. Mean BP at baseline,
      dismissal, and latest follow-up for group 1 were 132 +/- 4/73 +/- 2, 130 +/- 6/70
      +/- 2, and 125 +/- 3/73 +/- 3 mm Hg (P = not significant). Mean BP for group 2 at
      the same intervals were 150 +/- 4/80 +/- 2, 139 +/- 3 (P < .01 v baseline)/75 +/-
      2, 133 +/- 2 (P < .01 v baseline and < .05 v dismissal)/74 +/- 1 (P < .01 v
      baseline). The BP control rate (blood pressures less than 140/90 mm Hg) was 75%
      in group 2. Drug number/dose remained the same or lower in 87% and 91% of
      patients during follow-up in groups 1 and 2, respectively. These results suggest
      that a clinically significant lowering of blood pressure can often be achieved
      over several days and maintained for up to 1 year. Increased use of rapid drug
      titration, a physician-nurse team approach, and self-BP measurement at prescribed
      intervals have the potential to improve BP control rates and reduce the expense
      and inconvenience associated with the treatment of hypertension.

PMID- 11336181
TI  - Family history of hypertension and left ventricular mass in youth: possible
      mediating parameters.
AB  - Whether positive family history (FH) of essential hypertension (EH) in
      normotensive youth is associated with increased left ventricular mass (LVM) and
      hemodynamic, anthropometric, and demographic parameters previously associated
      with increased LVM in adults is unknown. To examine these issues, 323 healthy
      youth (mean age, 13.6 +/- 1.3 years), 194 with positive FH of EH (61% African
      Americans, 39% whites) and 129 with negative FH of EH (33% African Americans, 67%
      whites) were evaluated. Hemodynamics were measured at rest and during four
      stressors (ie, postural change, car driving simulation, video game, forehead
      cold). Echocardiographic-derived measures of LVM were indexed separately to body
      surface area and height(2.7). Controlling for age and race differences (ie, 74%
      of African Americans v 47% of whites had positive FH), the positive FH group
      exhibited greater LVM/height(2.7), LVM/body surface area, higher systolic (SBP)
      and diastolic blood pressures (DBP), and total peripheral resistance index (TPRI)
      and lower cardiac index at rest (P < .05 for all). The positive FH group also
      displayed higher peak SBP or DBP and higher TPRI increases to each stressor and
      came from lower socioeconomic status backgrounds (P < .05 for all). Regression
      analyses indicated that FH of EH was not a significant determinant of
      LVM/height(2.7) after accounting for contributions of gender (greater in men),
      general adiposity, resting cardiac index and blood pressure (BP), and TPRI
      responsivity to video game and cold stimulation (P < .05 for all). Thus, greater
      LVM index in positive FH of EH youth appears in part related to their greater BP
      and TPRI at rest and during stress.

PMID- 11336182
TI  - Familial dyslipidemic hypertension syndrome: familial combined hyperlipidemia,
      and the role of abdominal fat mass.
AB  - Familial combined hyperlipidemia (FCHL) is the most frequent genetic lipid
      abnormality in humans, with a 5- to 10-fold increased risk of early myocardial
      infarction. Familial combined hyperlipidemia has been proposed as the leading
      cause of dyslipidemia in familial dyslipidemic hypertension (FDH). It was the
      objective of this study to quantify and analyze the simultaneous occurrence of
      hypertension and hyperlipidemia in FCHL families. We assessed blood pressure (BP)
      and hyperlipidemia in 27 families with FCHL (235 relatives and 140 spouses, aged
      30 to 60 years). Hypertension was defined as a BP more than 140/90 mm Hg, or the
      use of antihypertensive medication. Multiple backward linear regression analysis
      was used to derive a biological formula describing BP in FCHL families. One-third
      of 27 FCHL families were diagnosed with FDH. Sixty-four of 235 (27.2%) relatives
      had dyslipidemic hypertension (DH), compared to 20 of 140 (14.3%) spouses (P =
      .005); odds ratio = 2.25 (95% confidence interval 1.29-3.91). Multiple linear
      regression analysis showed that age, FCHL status, and waist circumference
      significantly contributed to systolic blood pressure (SBP) in female FCHL
      relatives. In conclusion, in FCHL we defined age, waist circumference, and
      hyperlipidemia as predictors of SBP. This study indicates that visceral adipose
      tissue strongly contributes to the high prevalence of DH in FCHL families.
      Reduction of visceral fat should be tested as a potential therapeutic
      intervention for hyperlipidemia and hypertension in FCHL individuals.

PMID- 11336183
TI  - Angiotensin II AT1 receptor gene polymorphism and microalbuminuria in essential
      hypertension.
AB  - The objective of this study was to analyze the relationship of polymorphisms of
      the angiotensin II AT1 receptor gene with microalbuminuria in a group of young
      adults with essential hypertension. Essential hypertensives, less than 50 years
      old, never previously treated with antihypertensive drugs, and in absence of
      diabetes mellitus were included. Office blood pressure (BP), 24-h ambulatory BP
      monitoring, urinary albumin excretion (UAE) measurements, and DNA analysis were
      performed. Polymorphisms of the angiotensin II AT1-receptor gene (A1166C and
      C573T) were studied by polymerase chain reaction and single-strand conformation
      polymorphism techniques. One hundred eighty-three patients, 49 (27%)
      microalbuminurics, were included. Office and ambulatory BP values were
      significantly higher in the microalbuminuria group. No differences in the
      presence of microalbuminuria were observed among the genotypes of either A1166C
      or C573T polymorphisms of the angiotensin II receptor AT1 gene, or in the allele
      frequency of the A1166C or the C573T polymorphism. LogUAE was significantly
      different among genotypes of the C573T polymorphism [CC 1.30(1.15-1.45), CT
      1.14(1.00-1.28), and TT 0.94(0.68-1.20), P < .05]. Both office and ambulatory
      blood pressure and the TT/C573T genotype were independently related to logUAE,
      and, at the same BP values, UAE was lower in subjects with this genotype. We have
      found that the C573T polymorphism is on linkage disequilibrium with A1166C, as
      the 573T allele is closely linked to the presence of the 1166A allele, but not
      vice versa. Haplotype analysis among subjects with the AA genotype for the A1166C
      polymorphism confirms the influence of the TT genotype of the C573T polymorphism
      on the UAE in hypertensives. The C573T polymorphism of the angiotensin II
      receptor AT1 gene seems to be a genetic protective factor for UAE in a population
      of essential hypertensives.

PMID- 11336184
TI  - 5,10-Methylenetetrahydrofolate reductase polymorphism and early organ damage in
      primary hypertension.
AB  - Hyperhomocyst(e)inemia is a known risk factor for the development of
      atherosclerotic vascular damage. Plasma homocyst(e)ine levels are influenced by
      nutritional and hereditary factors. A point mutation (cytosine to thymidine
      substitution; C677T) in the gene encoding 5,10-methylenetetrahydrofolate
      reductase (MTHFR) makes the enzyme thermolabile and has been associated with
      elevated homocyst(e)ine levels in homozygous carriers (TT genotypes). We
      evaluated the relationship between the T allele encoding for the thermolabile
      variant of MTHFR and several biochemical risk factors and early signs of
      hypertensive and atherosclerotic organ damage in 206 untreated patients with
      primary hypertension. The MTHFR genotype was evaluated by polymerase chain
      reaction. Albuminuria was measured as albumin-to-creatinine ratio in three
      nonconsecutive first morning urine samples (negative urine culture). Persistent
      Mi (Alb+) was defined as an average albumin-to-creatinine ratio between 2.38 and
      19 (men) and 2.96 and 20 (women). Left ventricular (LV) mass index (LVMI) was
      assessed by M-B mode echocardiography (LV hypertrophy, LVH = LVMI > or = 125
      g/m2), carotid geometry by high-resolution ultrasound scan, and retinal vascular
      changes by direct ophthalmoscopy (Keith-Wagener classification). The prevalence
      of Mi, LVH, and retinopathy was 14%, 45%, and 42%, respectively. The prevalence
      of carotid plaque was 25%. Allele frequencies for C (wild-type allele) and T
      allele (mutant allele) were 56% and 44%, respectively. Genotype frequencies were
      CC 29%, CT 54%, TT 17% according to Hardy Weinberg equilibrium. There were no
      differences as for age, sex, body mass index, blood pressure levels, lipid
      profile, smoking habits, and alcohol intake, and LVMI and urinary albumin
      excretion on the basis of MTHFR genotype. Patients with TT polymorphism showed a
      higher prevalence of retinal vascular changes (TT, 61% v CT + CC, 38%; P < .02)
      and carotid plaque (TT, 42% v CT + CC, 21%; P < .05) compared to patients with CC
      and CT polymorphism. Moreover, patients with T allele showed increased carotid
      artery size as demonstrated by intima plus media thickness (IT, 0.79 +/- 0.05 mm
      v CT + CC, 0.67 +/- 0.02 mm; P < .02), relative wall thickness (TT, 0.23 +/- 0.01
      mm v CT + CC, 0.20 +/- 0.005 mm; P < .02), and surface area (TT, 19 +/- 1.9 mm2 v
      CT + CC, 15 +/- 0.55 mm2; P < .05). Multiple linear regression analysis
      demonstrated that MTHFR genotype and systolic blood pressure independently
      influence intima-media thickness and together account for about 11% of its
      variations (r2 = 0.11, F = 9.7, dF = 1-205, P < .0001). Homozygosity for the T
      allele of the MTHFR gene is an independent risk factor for the development of
      early atherosclerotic organ damage in hypertensive patients.

PMID- 11336185
TI  - The effects of allicin and enalapril in fructose-induced hyperinsulinemic
      hyperlipidemic hypertensive rats.
AB  - The effects of a synthetic preparation of an active constituent of garlic,
      allicin, were studied on blood pressure (BP), triglycerides, and insulin levels
      in Sprague-Dawley rats in which high fructose feeding elicited hyperinsulinemia,
      hypertension, and hypertriglyceridemia. Results were compared with those of the
      antihypertensive drug enalapril. Three groups of male Sprague-Dawley rats were
      fed a fructose-enriched diet for 5 weeks. During the last 2 weeks 10 animals
      received only fructose, 10 received allicin, and 10 received enalapril. Blood
      pressure, insulin level, and triglyceride levels were measured at the beginning
      of the experiment and after 3 and 5 weeks on the fructose diet, fructose/allicin
      diet, or fructose/enalapril diet. Allicin lowered BP from the maximal level
      (after 3 weeks of fructose) of 153.4 +/- 8 mm Hg to 139.7 +/- 12 mm Hg after 2
      weeks on allicin; insulin from 11.7 +/- 3.7 ng/mL on fructose diet to 6.92 +/-
      3.3 ng/mL on allicin; and triglycerides from 132.8 +/- 18 mg/dL on fructose to
      59.6 +/- 27 mg/dL on allicin. The similar effect of allicin and enalapril on BP,
      insulin, and triglycerides reinforces the trend toward combining the
      nonpharmacologic approach with drug therapy.

PMID- 11336186
TI  - Decreased nitric oxide levels and increased calcium content in platelets of
      hypertensive patients.
AB  - Decreased levels of nitric oxide (NO) may contribute to impaired endothelium
      dependent vasodilatation in essential hypertension. Moreover, in hypertension,
      major platelets aggregation and endothelial adhesion, and increased atherogenetic
      risks are also present. Nitric oxide produced by platelet NO synthase, which is
      similar to endothelial NO synthase, inhibits platelets aggregation by increasing
      cytoplasmic cyclic GMP levels and contributes in a major way to the
      antithrombogenic properties of endothelium. The aim of this study was to
      investigate platelet NO production and cytosolic Ca2+ levels in patients with
      essential hypertension and in healthy subjects. We studied NO production in 36
      subjects (21 patients had essential hypertension and 15 subjects were
      normotensive); NO synthase activity was evaluated by measuring nitrite levels by
      the Griess reaction in the supernatant of sonicated platelets. Cytosolic Ca2+
      levels were measured in intact platelets using the fluorescent probe Fura 2-AM.
      Nitric oxide levels in platelets were found higher in normotensive than in
      hypertensive patients (P < .0001). Nitric oxide levels in hypertensive women were
      significantly higher than in hypertensive men (P < .001). Hypertensive women and
      men had lower levels of nitrite than normotensive women and men (P < .001 and P <
      .002, respectively). Platelet cytosolic Ca2+ levels were higher in hypertensive
      patients than in normotensive subjects (P < .001). An inverse correlation was
      found between platelet cytosolic Ca2+ and NO levels (r = 0.74, P < .002). These
      data confirm the link between hypertension and altered platelets function and
      suggest a role for NO in cardiovascular events. Moreover, the higher levels of
      nitric oxide in child-bearing age women than in men further support the
      protective effect of estrogens on cardiovascular diseases.

PMID- 11336187
TI  - Decreased influence of nitric oxide on deoxycorticosterone acetate (DOCA)-salt
      hypertension.
AB  - The response to exogenous administration of acetylcholine and the effects of
      nitric oxide (NO) synthesis blockade were assessed for small arterioles in the
      cremaster muscle of deoxycorticosterone acetate (DOCA)-salt hypertensive and
      normotensive rats using intravital microscopy. The NO synthesis inhibitor N omega
      L-nitro-arginine methyl ester (L-NAME) produced significantly less constriction
      in the arterioles of DOCA-salt hypertensive rats. Exposure to increasing
      concentrations of acetylcholine (10(-10) to 10(-5) mol/L) or sodium nitroprusside
      (10(-10) to 10(-5) mol/L) produced similar arteriolar dilation in both groups.
      These results suggest that attenuated basal release of NO by arterioles may play
      a role in the development of increased peripheral resistance observed in DOCA
      salt hypertension.

PMID- 11336189
TI  - Classic images in hypertension. Aortic dissection in a hypertensive patient.

PMID- 11336188
TI  - Dimensions of the left ventricle, atrium, and aortic root in pregnancy-induced
      hypertension.
AB  - Chronic hypertension induces changes in the structure of the left ventricle,
      atrium, and aortic root. However, the effects of transient hypertension are
      unclear. Pregnancy-induced hypertension (PIH) offers a natural and spontaneous
      model of this condition. Using M-mode echocardiography, we studied 95 consecutive
      patients with PIH, who were compared with 83 normal pregnant women (NPW). We
      evaluated diastolic diameter (DD), systolic diameter (SD), septal thickness (ST),
      posterior wall thickness (PWT), shortening fraction (SF), relative wall thickness
      (RWT), left ventricular mass index (LVMI), left atrial dimension (LAD), and
      aortic root dimension (ARD). Patients with PIH had higher ST (9.98 +/- 1.47 mm v
      8.96 +/- 1.43 mm, P < .000), PWT (9.28 +/- 1.48 mm v 8.55 +/- 1.35 mm, P < .000),
      LVMI (107.65 +/- 27.87 g/m2 v 92.38 +/- 17.99 g/m2, P < .000), and RWT (0.406 +/-
      0.06 v 0.377 +/- 0.06 mm, P < .002). There were no significant differences in DD,
      SD, SF, LAD, and ARD. In conclusion, PIH increases the LVMI due to an increase in
      the ST and PWT. The dimensions of the left ventricle, left atrium, and aortic
      root do not change.

PMID- 11336190
TI  - Angiotensin II antagonists for hypertension: there are differences in efficacy.

PMID- 11336191
TI  - The mesenteric hemodynamic response to circulatory shock: an overview.
AB  - The mesenteric hemodynamic response to circulatory shock is characteristic and
      profound; this vasoconstrictive response disproportionately affects both the
      mesenteric organs and the organism as a whole. Vasoconstriction of post-capillary
      mesenteric venules and veins, mediated largely by the alpha-adrenergic receptors
      of the sympathetic nervous system, can effect an "autotransfusion" of up to 30%
      of the total circulating blood volume, supporting cardiac filling pressures
      ("preload"), and thereby sustaining cardiac output at virtually no cost in
      nutrient flow to the mesenteric organs. Under conditions of decreased cardiac
      output caused by cardiogenic or hypovolemic shock, selective vasoconstriction of
      the afferent mesenteric arterioles serves to sustain total systemic vascular
      resistance ("afterload"), thereby maintaining systemic arterial pressure and
      sustaining the perfusion of non-mesenteric organs at the expense of mesenteric
      organ perfusion (Cannon's "flight or fight" response). This markedly
      disproportionate response of the mesenteric resistance vessels is largely
      independent of the sympathetic nervous system and variably related to
      vasopressin, but mediated primarily by the renin-angiotensin axis. The extreme of
      this response can lead to gastric stress erosions, nonocclusive mesenteric
      ischemia, ischemic colitis, ischemic hepatitis, ischemic cholecystitis, and/or
      ischemic pancreatitis. Septic shock can produce decreased or increased mesenteric
      perfusion, but is characterized by an increased oxygen consumption that exceeds
      the capacity of mesenteric oxygen delivery, resulting in net ischemia and
      consequent tissue injury. Mesenteric organ injury from ischemia/reperfusion due
      to any form of shock can lead to a triggering of systemic inflammatory response
      syndrome, and ultimately to multiple organ dysfunction syndrome. The mesenteric
      vasculature is therefore a major target and a primary determinant of the systemic
      response to circulatory shock.

PMID- 11336192
TI  - Trauma severity-dependent changes in AT III activity.
AB  - Trauma may cause a relevant reduction in antithrombin (AT) III activity, which is
      associated with adverse events. The very early changes in AT III activity after
      accident trauma are still unclear and possible relations with Interleukin (IL)-6,
      which is known to interact with AT III, have not been investigated so far. Upon
      approval of the IRB/IEC, 30 patients were enrolled with multiple injuries (ISS 9
      75). Groups were performed according to injury severity, IL-6 concentration, and
      survivors versus non-survivors. Blood samples were collected at the scene of
      accident then at 2, 4, 6, 12, and 24 h and at day 3, 5, 10 and 15. No patient
      received AT III concentrates. In all groups a reduction in AT III activity
      occurred, which was most pronounced in very severe injuries. The activity re
      increased spontaneously and steadily in all groups regardless of the IL-6
      concentration. There was no clear impact of the AT III activity on survival.

PMID- 11336193
TI  - Characterization of multiple organ dysfunction syndrome in very low birthweight
      infants: a new sequential scoring system.
AB  - To define multiple organ dysfunction in newborns, we established a sequential
      scoring system NEOMOD (Neonatal Multiple Organ Dysfunction Score). It was
      developed to describe the process of increasing physiologic derangement in
      critically ill newborns. It provides, during the first 28 days of life,
      information concerning function of organ systems having a primary influence on
      mortality in very low birth weight (VLBW) infants. Our scoring system has been
      used in 142 VLBW infants. It evaluates moderate (1 point) or severe dysfunction
      (2 points) in 7 organ systems (central nervous system, cardiovascular, renal,
      respiratory, and gastrointestinal systems, and hemocoagulation and acid-base
      balance) in 24-h intervals from day 1 to 28 of life. Maximum possible value of
      NEOMOD was 14 points. Receiver operating characteristic curve was used for
      assessing predictive accuracy of maximum NEOMOD score obtained by daily scoring
      for mortality rate. AUC (area under curve) attained by NEOMOD was 0.95 for
      mortality within the first 28 days and 0.91 for hospital mortality, respectively.
      In the study group, NEOMOD score of > or = 9 was associated with 100% mortality.
      An analysis of specific organ dysfunctions in the non-survivors group (n = 16)
      disclosed, in all patients, dysfunction of more than two organ systems 24 h
      before death. Similar to critically ill adults, secondary multiple organ
      dysfunction can be described also in a majority of critically ill VLBW infants.
      NEOMOD scores may help to evaluate daily the severity of the syndrome and risk of
      death.

PMID- 11336194
TI  - Effects of hypertonic saline solution on mesenteric microcirculation.
AB  - We evaluated systemic and microvascular effects of hypertonic NaCl solution on
      normovolemic and hemorrhaged animals. Forty-three Wistar rats (186 +/- 4 g, mean
      +/- SEM) were anesthetized with pentobarbital and cannulated for mean arterial
      pressure (MAP), heart rate (HR), and mean pulse pressure (MPP) monitoring and
      blood withdrawal. Diameters of 126 arterioles and 88 venules of the exteriorized
      mesentery were studied by using intravital microscopy. Microvascular blood flow
      was calculated from diameter and red blood cell velocity measurements. The
      protocol consisted of 15 min control, 30 min hypotension (MAP = 52.9 +/- 0.9
      mmHg, hemorrhaged vol. = 17.1 +/- 0.7 mL/kg) and 60 min post-infusion of either
      normal (0.9%) or hypertonic saline (7.5%, 4 mL/kg). Normovolemic animals showed
      no systemic or microvascular effects of hypertonic saline. Hemorrhagic
      hypotension resulted in HR fall that was not changed after infusions. Hypertonic
      infusion reversed MPP decrease during hypotension but only partially restored MAP
      and microvascular blood flow. Venules did not change diameter during protocols.
      During hypotension, 24% of arterioles displayed vasomotion (38% of the rats) with
      low- and high-frequency components present in 74% and 87% of arterioles,
      respectively. Arterioles with vasomotion during hypotension had larger control
      diameters (28.9 +/- 2.0 microm) and contracted more (30.8 +/- 4.1%) than
      arterioles without vasomotion (18.7 +/- 1.2 microm and 8.1 +/- 1.5%,
      respectively). Mean arteriolar diameter did not change after infusions. After
      hypertonic solution, the number of vessels showing vasomotion increased 80%,
      frequency of vasomotion was unchanged, and amplitude increased. These findings
      may help to explain some of the mechanisms underlying resuscitation effects of
      hypertonic infusions during hemorrhagic hypotension.

PMID- 11336195
TI  - Monitoring gastrointestinal intraluminal PCO2: problems with airflow methods.
AB  - Gastrointestinal intraluminal PCO2 (PiCO2) information is used to assess the
      adequacy of trauma patient resuscitation and to assist in choosing resuscitative
      interventions. Therefore, determining the limitations and potential caveats of
      different PiCO2 monitoring systems is clinically important. This study compared
      two PCO2 monitoring systems. The airflow device adds and then removes air samples
      to quantitate PCO2, whereas the fiber-optic device does not. METHODS: Airflow
      (TRIP Tonometer/Tonocap) and fiber-optic (Neotrend) systems were used. In vitro
      they were compared with each other and to two end-tidal CO2 monitors measuring
      the PCO2 of humidified air containing 5% and then 10% CO2. In vivo the two
      systems' catheters were surgically juxtaposed in 15 dogs' stomachs; paired PiCO2
      readings were taken throughout hemorrhage and resuscitation. RESULTS: In vitro,
      paired PCO2 values from the airflow and fiber-optic devices correlated with each
      other (r = 0.99) and with end-tidal values (r = 0.99 with airflow, r = 0.95 with
      fiber-optic). In vivo, paired values differed significantly (P < 0.0001),
      correlating poorly for two devices simultaneously measuring the same variable (r
      = 0.61). Fiber-optic PiCO2 values were higher than airflow values (mmHg +/- SEM):
      69.3 +/- 4.8 vs. 61.3 +/- 5.6 at the start of hemorrhage, 141.3 +/- 12.9 vs. 87.7
      +/- 7.9 by end of hemorrhage, and 104.3 +/- 9.6 vs. 82.8 +/- 7.0 by end of
      resuscitation for fiber-optic and airflow, respectively. CONCLUSIONS: Despite
      agreement in vitro, airflow methods can influence PiCO2 values obtained in vivo.
      Passive sensing methods used to monitor PiCO2, such as fiber-optic methods, are
      preferable because they neither deliver O2 to, nor remove CO2 from the local
      microenvironment.

PMID- 11336196
TI  - Organ specific formation of nitrosyl complexes under intestinal
      ischemia/reperfusion in rats involves NOS-independent mechanism(s).
AB  - Intestinal ischemia/reperfusion may lead to local and distant organ damage
      involving nitric oxide (NO). NO rapidly reacts with heme/non-heme-iron-yielding
      nitrosyl complexes, which can be determined directly by electron paramagnetic
      resonance spectroscopy. The aim of the present study was to characterize
      nitrosylation reactions induced by transient intestinal ischemia in blood and
      tissues. We used electron paramagnetic resonance spectroscopy and reverse
      transcription polymerase chain reaction analyses to estimate nitrosyl complex
      levels and inducible NO synthase mRNA expression in rats subjected to superior
      mesenteric artery occlusion for 60 min followed by the reperfusion. Nitrosyl
      hemoglobin concentrations in circulating blood were significantly increased
      during ischemia and reperfusion. Nitrosyl hemoglobin complexes were detected in
      ischemic intestine, but not in normoxic lung and liver or reperfused intestine.
      Administration of N-G-monomethyl-L-arginine, a non-specific NO synthase
      inhibitor, did not affect the formation of circulating nitrosyl complexes.
      Moreover, inducible NO synthase mRNA was not found in intestinal tissues at 30
      min of reperfusion. Our data suggest an organ-specific NO formation indicated by
      the increased nitrosylation reaction in ischemic intestinal tissue, but not in
      the distant normoxic organs, in spite of high circulating nitrosyl hemoglobin
      levels. NO involved in nitrosylation under intestinal ischemia/reperfusion is
      probably formed by NO synthase-independent mechanism(s).

PMID- 11336197
TI  - Influence of temperature during cardiopulmonary bypass on leukocyte activation,
      cytokine balance, and post-operative organ damage.
AB  - This study examined the hypothesis that core temperature (T(o)) during
      cardiopulmonary bypass (CPB) influences the perioperative systemic inflammatory
      response and post-operative organ damage. Twenty-four pigs were assigned to a
      T(o) regimen during CPB: normothermia (T(o) 37 degrees C; n = 8), moderate
      hypothermia (T(o) 28 degrees C; n = 8), or deep hypothermia (T(o) 20 degrees C; n
      = 8). Perioperative leukocyte activation, endotoxin release, and production of
      tumor necrosis factor-alpha (TNFalpha) and interleukin-10 (IL10) were examined
      with regard to post-operative organ damage, which was scored at histological
      examination of tissue probes of heart, lungs, liver, kidney, and ileum, taken 6 h
      after CPB. Total blood leukocyte count and TNFalpha plasma levels during CPB were
      significantly lower and IL10 levels were significantly higher in the moderate
      hypothermic group than in both other groups. Elastase activity, leukotriene B4-,
      and endotoxin levels were not affected by T(o) regimen. Moderate hypothermia was
      associated with the lowest histological organ damage score and normothermia with
      the highest. In all animals organ damage score for heart, lungs, and kidneys
      correlated significantly with TNFalpha levels at the end of CPB. Our data
      demonstrate a clear relationship between TNFalpha production during cardiac
      operations and post-operative multiple-organ damage. Moderate hypothermia, by
      stimulating IL10 synthesis and suppressing TNFalpha production during CPB, might
      provide organ protection.

PMID- 11336198
TI  - Effects of nucleoside transport inhibition on hepatosplanchnic perfusion, oxygen
      extraction capabilities, and TNF release during acute endotoxic shock.
AB  - We explored the effects of the nucleoside transport inhibitor draflazine on
      regional blood flow, O2 extraction capabilities, and tumor necrosis factor (TNF)
      release in acute endotoxic shock. Fourteen anesthetized and mechanically
      ventilated dogs received 2 mg/kg of Escherichia coli endotoxin and were divided
      into two groups. Seven dogs received 0.1 mg/kg of draflazine 30 min before
      endotoxin, and 7 dogs served as a control group. Draflazine decreased arterial
      pressure without influencing cardiac index. Mesenteric and portal blood flow and
      ileum mucosal perfusion increased, but renal blood flow dramatically decreased.
      After endotoxemia, the draflazine-treated dogs had a lesser fall in cardiac
      index, filling pressures, and left ventricular stroke work index, and a lesser
      increase in pulmonary vascular resistance. After fluid resuscitation, they had a
      consistently lower renal blood flow and ileum mucosal perfusion, but a higher
      mixed venous and hepatic oxygen saturation and arterial pH than the control
      group. When cardiac index was reduced by tamponade to study the O2 extraction
      capabilities, renal blood flow and ileum mucosal perfusion remained lower in the
      draflazine group. Draflazine did not influence whole-body O2 extraction
      capabilities, but it delayed the occurrence of liver O2 supply dependency as
      indicated by a significantly lower liver DO2crit (27.7 +/- 3.9 vs. 43.3 +/- 10.8
      mL/min) and a higher O2ERcrit (62.7 +/- 9.5 vs. 42.5 +/- 7.1%) than controls
      (both P< 0.05). On the other hand, draflazine increased intestinal DO2crit (42.4
      +/- 15.4 vs. 27.7 +/- 6.5 mL/min, P < 0.05) compared to the control group. TNF
      levels remained higher in the draflazine group than in the control group,
      particularly 3 and 4 h after endotoxin administration. We conclude that
      nucleoside transport inhibition with draflazine does not alter global and
      hepatosplanchnic hemodynamics but may decrease gut mucosal perfusion and renal
      blood flow. However, this intervention can improve liver O2 extraction
      capabilities in acute endotoxic shock.

PMID- 11336199
TI  - Endotoxin impairs agonist-stimulated intracellular free calcium (Ca(i)) responses
      in freshly dispersed aortic endothelial cells.
AB  - Impairment in endothelial cell intracellular free calcium (Ca(i)) mobilization
      mechanisms may contribute to decreased nitric oxide (NO) biosynthesis and
      impaired vasorelaxation responses of endotoxemic guinea pigs to endothelium
      dependent vasodilators. We tested this hypothesis using fura-2 microfluorometry
      to compare agonist-stimulated Ca(i) responses of aortic endothelial cells freshly
      dispersed from guinea pigs 16 h after intraperitoneal injection of Escherichia
      coli endotoxin (lipopolysaccharide, LPS; 4 mg/kg) or saline (CON). In the
      presence of normal extracellular Ca2+ (2 mmol/L), basal (non-stimulated)
      endothelial Ca(i) (340/380 nm fluorescence ratio, R) was not different between
      CON and LPS cells (1.1 +/- 0.03 and 1.1 +/- 0.03, respectively). However,
      exposure to ADP (10 micromol/L) produced a biphasic increase in Ca(i) that was
      markedly decreased in cells from LPS-treated animals (P < 0.0001). Peak ADP
      stimulated Ca(i) responses averaged 2.2 +/- 0.21 in CON cells and 1.5 +/- 0.11 (P
      < 0.01) in cells dispersed from LPS-treated animals. Exposure to acetylcholine
      (ACh; 10 micromol/L) produced sustained increases in Ca(i) (R = 1.4 +/- 0.13) in
      CON cells; however, LPS abolished Ca(i) responses to ACh. Exposure of endothelial
      cells to substance P (100 nmol/L) produced a biphasic increase in Ca(i) that was
      not different between groups. In the absence of extracellular Ca2+ (plus 10
      micromol/L EGTA), exposure to ADP (10 micromol/L) produced transient increases in
      Ca(i) (Ca2+ release) that were decreased in cells from LPS-treated versus CON
      animals. Exposure to ACh in zero Ca2+ (10 micromol/L) produced smaller increases
      in Ca(i) (peak R = 1.3 +/- 0.12) in CON cells (when compared to ADP); however,
      Ca(i) responses to ACh remained absent in cells from LPS-treated animals. Re
      exposure to Ca2+ produced sustained ACh-induced Ca(i) responses (Ca2+ influx) in
      cells from CON, but not LPS-treated animals; LPS markedly impaired (P< 0.05) ADP
      induced sustained Ca(i) responses. Our data demonstrate that in vivo LPS exposure
      elicits decreased agonist-stimulated endothelial Ca(i) responses primarily
      involving impaired Ca2+ influx mechanisms. Known dependence of endothelial
      agonist-stimulated NO synthesis on Ca(i) suggests that defects in cell Ca2+
      mobilization may contribute to LPS-induced impaired NO biosynthesis and decreased
      endothelium-dependent relaxation.

PMID- 11336200
TI  - Near-infrared and nuclear magnetic resonance spectroscopic assessment of tissue
      energetics in an isolated, perfused canine hind limb model of dysoxia.
AB  - This controlled laboratory study examined the efficacy of near-infrared
      spectroscopy (NIRS) and 31P-nuclear magnetic resonance (NMR) spectroscopy in
      measuring regional tissue oxygenation in a isolated, perfused hind limb model of
      tissue dysoxia. Isolated hind limb perfusion was carried out in 20 mongrel dogs
      and oxygen delivery was varied by manipulating either hemoglobin concentration,
      oxygen saturation, or flow. Hind limbs from anesthetized mongrel dogs (n = 20)
      were separated and isolated perfusion performed. NIRS probes for recording
      relative O2 saturation of tissue hemoglobin (HbO2) and cytochrome a,a3 and NMR
      probes for measuring 31P-high energy phosphates were placed over the limb.
      Measurements of physiologic parameters, blood gases, lactate, NIRS values for
      HbO2 and cytochrome a,a3 redox state, and 31P-phosphate levels were recorded at
      set intervals throughout the experiment. Measures of tissue oxygen consumption
      (VO2) correlated with tissue oxygenation as measured by HbO2 and cytochrome a,a3
      redox state (NIRS), as well as by 31P-high energy phosphate levels (NMR)
      throughout the experiment. Delivery-dependent tissue oxygenation was detected at
      a higher DO2 by NIRS than by VO2 or NMR. Tissue oxygenation as measured by NIRS
      and NMR shows excellent correlation with oxygen delivery in an isolated, perfused
      model of shock. NIRS may allow early detection of tissue dysoxia using rapid non
      invasive techniques.

PMID- 11336201
TI  - Decreases in mesenteric blood flow associated with increases in sublingual PCO2
      during hemorrhagic shock.
AB  - We investigated relationships between visceral blood flow, intestinal wall carbon
      dioxide tension (PCO2), and sublingual PCO2 during hemorrhagic shock. In five
      pigs, cardiac output declined 81% and superior mesenteric blood flow 77% during
      hemorrhage. Duodenal PCO2 increased from an average of 50 to 121 mmHg and
      sublingual PCO2 concurrently increased from an average of 46 to 101 mmHg. Within
      60 min after reinfusion of shed blood, duodenal and sublingual PCO2 returned to
      baseline values. Decreases in mesenteric blood flow were correlated with
      increases in sublingual (r = 0.91; P < 0.001) and duodenal (r = 0.89; P < 0.001)
      tissue PCO2. In five randomized "sham hemorrhage" control animals, neither
      decreases in cardiac output or mesenteric blood flow nor increases in duodenal or
      sublingual PCO2 were observed. Decreases in mesenteric blood flow during
      hemorrhage were therefore associated with early and comparable increases in
      tissue PCO2 in both visceral and sublingual sites.

PMID- 11336202
TI  - Alteration in Kupffer cell function after mild hemorrhagic shock.
AB  - Functional changes in Kupffer cells occur after profound hemorrhagic shock. This
      study was performed to demonstrate if Kupffer cell changes also occur after mild
      hemorrhagic shock. Sprague-Dawley rats were bled to a systolic blood pressure of
      60 to 70 mmHg and resuscitated with Lactated Ringers solution (twice the shed
      blood volume) after 30 min. Resuscitation produced immediate recovery of blood
      pressure and allowed long-term recovery of the animals. Sham animals received
      anesthesia and monitoring only. Thirty minutes after resuscitation, Kupffer cells
      were isolated by centrifugal elutriation and cultured for 48 h. In Kupffer cells
      isolated from shocked animals, phorbol ester-stimulated superoxide production
      increased 7-fold and lipopolysaccharide- (LPS) stimulated prostaglandin E2 (PGE2)
      production increased 4-fold. Tumor necrosis factor-alpha (TNFalpha) production,
      on the other hand, was decreased by 50%. A non-significant trend toward increased
      phagocytosis was also observed, whereas LPS-stimulated nitric oxide production
      was unchanged. In conclusion, mild hemorrhagic shock produced increases in
      superoxide and PGE2 production, and decreases in TNFalpha production by Kupffer
      cells, changes that may be appropriate to defend against the infectious
      challenges that often follows trauma and hemorrhage.

PMID- 11336203
TI  - Effect of rotation and translation on the expected benefit of an ideal method to
      correct the eye's higher-order aberrations.
AB  - An ideal correcting method, such as a customized contact lens, laser refractive
      surgery, or adaptive optics, that corrects higher-order aberrations as well as
      defocus and astigmatism could improve vision. The benefit achieved with this
      ideal method will be limited by decentration. To estimate the significance of
      this potential limitation we studied the effect on image quality expected when an
      ideal correcting method translates or rotates with respect to the eye's pupil.
      Actual wave aberrations were obtained from ten human eyes for a 7.3-mm pupil with
      a Shack-Hartmann sensor. We computed the residual aberrations that appear as a
      result of translation or rotation of an otherwise ideal correction. The model is
      valid for adaptive optics, contact lenses, and phase plates, but it constitutes
      only a first approximation to the laser refractive surgery case where tissue
      removal occurs. Calculations suggest that the typical decentrations will reduce
      only slightly the optical benefits expected from an ideal correcting method. For
      typical decentrations the ideal correcting method offers a benefit in modulation
      2-4 times higher (1.5-2 times in white light) than with a standard correction of
      defocus and astigmatism. We obtained analytical expressions that show the impact
      of translation and rotation on individual Zernike terms. These calculations also
      reveal which aberrations are most beneficial to correct. We provided practical
      rules to implement a selective correction depending on the amount of
      decentration. An experimental study was performed with an aberrated artificial
      eye corrected with an adaptive optics system, validating the theoretical
      predictions. The results in a keratoconic subject, also corrected with adaptive
      optics, showed that important benefits are obtained despite decentrations in
      highly aberrated eyes.

PMID- 11336204
TI  - Information limit on the spatial integration of local orientation signals.
AB  - Channel-based models of human spatial vision require that the output of spatial
      filters be pooled across space. This pooling yields global estimates of local
      feature attributes such as orientation that are useful in situations in which
      that attribute may be locally variable, as is the case for visual texture. The
      spatial characteristics of orientation summation are considered in the study. By
      assessing the effect of orientation variability on observers' ability to estimate
      the mean orientation of spatially unstructured textures, one can determine both
      the internal noise on each orientation sample and the number of samples being
      pooled. By a combination of fixing and covarying the size of textured regions and
      the number of elements constituting them, one can then assess the effects of the
      texture's size, density, and numerosity (the number of elements present) on the
      internal noise and the sampling density. Results indicate that internal noise
      shows a primary dependence on texture density but that, counterintuitively,
      subjects rely on a sample size approximately equal to a fixed power of the number
      of samples present, regardless of their spatial arrangement. Orientation pooling
      is entirely flexible with respect to the position of input features.

PMID- 11336205
TI  - Multicriterion cross-entropy minimization approach to positron emission
      tomographic imaging.
AB  - A multicriterion cross-entropy minimization approach to positron emission
      tomographic (PET) imaging is described. An unexplored multicriterion cross
      entropy optimization algorithm based on weighted-sum scalarization is used to
      solve this problem. The efficacy of the algorithm is compared with that of the
      single-criterion optimization algorithm and the convolution backprojection method
      for image reconstruction from computer-generated projection data and Siemens PET
      scanner data. The algorithms described have been implemented on a PIII/686
      microcomputer.

PMID- 11336206
TI  - Iterative algorithm with a constraint condition for numerical reconstruction of a
      three-dimensional object from its hologram.
AB  - A novel method to obtain the three-dimensional mathematical model of a
      transparent object from its hologram is presented. The proposed method can
      numerically extract the object information from the fringe pattern of the
      hologram. Then an iterative algorithm is used to imitate an imaging system by
      focusing on different layers of the object; and by operating in both the spatial
      domain and the frequency domain, the algorithm produces a series of two
      dimensional layer images. The object is finally reconstructed layer by layer. A
      constraint condition should be satisfied, and the noise distribution can be
      rearranged in different reconstruction cycles so as to get better reconstruction
      quality. Numerical simulations have proved the effectiveness of the proposed
      method.

PMID- 11336207
TI  - Integer ambiguity resolution in phase closure imaging.
AB  - Phase calibration is the key operation of phase closure imaging. In the case of
      nonredundant arrays, the related problem amounts to finding the node of a Z
      lattice closest to the end of a vector, the components of which are the
      differences between the closure phases of the data and those of the model. The
      aim of the paper is to show that this integer ambiguity problem can be solved in
      a very efficient manner. Its potential instabilities can also be well identified.
      The corresponding approach, which can be extended to redundant arrays, revisits
      and completes the analysis presented in a recent paper entitled "Phase
      calibration on interferometric graphs" [J. Opt. Soc. Am. A 16, 443 (1999)]. The
      procedures of self-calibration must be modified accordingly. The spinoffs of this
      approach also concern the integer ambiguity problems encountered in the global
      positioning system.

PMID- 11336208
TI  - Flatland optics. II. Basic experiments.
AB  - In "Flatland optics: fundamentals" [J. Opt. Soc. Am. A 17, 1755 (2000)] we
      described the basic principles of two-dimensional (2D) optics and showed that a
      wavelength lambda in three-dimensional (3D) space (x,y,z) may appear in Flatland
      (x,z) as a wave with another wavelength, lambda = lambda/cosalpha. The tilt angle
      alpha can be modified by a 3D (Spaceland) individual who then is able to
      influence the 2D optics in a way that must appear to be magical to 2D Flatland
      individuals-in the spirit of E. A. Abbott's science fiction story [Flatland, a
      Romance of Many Dimensions, 6th ed. (Dover, New York, 1952)] of 1884. We now want
      to establish the reality or objectivity of the 2D wavelength lambda by some basic
      experiments similar to those that demonstrated roughly 200 years ago the wave
      nature of light. Specifically, we describe how to measure the 2D wavelength
      lambda by mean of five different arrangements that involve Young's biprism
      configuration, Talbot's self-imaging effect, measuring the focal length of a
      Fresnel zone plate, and letting light be diffracted by a double slit and by a
      grating. We also performed experiments with most of these arrangements. The
      results reveal that the theoretical wavelength, as predicted by our Flatland
      optics theory, does indeed coincide with the wavelength lambda as measured by
      Flatland experiments. Finally, we present an alternative way to understand
      Flatland optics in the spatial frequency domains of Flatland and Spaceland.

PMID- 11336209
TI  - Fast maximum-likelihood image-restoration algorithms for three-dimensional
      fluorescence microscopy.
AB  - We have evaluated three constrained, iterative restoration algorithms to find a
      fast, reliable algorithm for maximum-likelihood estimation of fluorescence
      microscopic images. Two algorithms used a Gaussian approximation to Poisson
      statistics, with variances computed assuming Poisson noise for the images. The
      third method used Csiszar's information-divergence (I-divergence) discrepancy
      measure. Each method included a nonnegativity constraint and a penalty term for
      regularization; optimization was performed with a conjugate gradient method.
      Performance of the methods was analyzed with simulated as well as biological
      images and the results compared with those obtained with the expectation
      maximization-maximum-likelihood (EM-ML) algorithm. The I-divergence-based
      algorithm converged fastest and produced images similar to those restored by EM
      ML as measured by several metrics. For a noiseless simulated specimen, the number
      of iterations required for the EM-ML method to reach a given log-likelihood value
      was approximately the square of the number required for the I-divergence-based
      method to reach the same value.

PMID- 11336210
TI  - Ultrashort pulse propagation in near-field periodic diffractive structures by use
      of rigorous coupled-wave analysis.
AB  - We present a method for near-field analysis of ultrashort optical pulse
      propagation in periodic structures-including subwavelength and resonant grating
      structures-based on the integration of Fourier spectrum decomposition and
      rigorous coupled-wave analysis (RCWA). We discuss the spectral decomposition,
      including considerations for computational efficiency, the application of the
      RCWA method to compute the internal and external fields of the structure, and the
      synthesis of the resulting fields to obtain the time-domain solution. We apply
      this tool to the analysis of two photonic structures: (1) a nanostructured
      polarization-selective mirror that exhibits the desired broadband performance
      characteristics when operated at the design wavelength but yields strongly
      diminished polarization selectivity and modulation of the pulse envelope at an
      offset wave-length and (2) a two-mode coupled waveguide structure that produces
      from one incident pulse two transmitted pulses whose temporal separation depends
      on the waveguide geometry. In both examples, we apply our new modeling tool to
      investigate the near fields and find that near-field effects are critical in
      determining the performance characteristics of nanostructured devices.
      Furthermore, detailed observation and understanding of near-field phenomena in
      nanostructures may be applied to the design of novel photonic devices.

PMID- 11336211
TI  - Wavelength-multiplexing diffractive phase elements: design, fabrication, and
      performance evaluation.
AB  - We report on the wavelength-multiplexing diffractive phase element (WMDPE)
      capable of generating independent spot patterns for different wavelengths. The
      iterative method proposed by Bengtsson [Appl. Opt. 37, 1998] for designing a
      kinoform that produces different patterns for two wavelengths is extended to the
      WMDPE for multiple wavelengths (more than two wavelengths). Effectiveness of the
      design algorithm is verified by design and computer simulations on the WMDPE's
      for four and nine wavelengths. The WMDPE for three wavelengths (441.6, 543.5, and
      633 nm) is designed with five phase levels and is fabricated by electron-beam
      lithography. We observed that the individual spot patterns are reconstructed for
      the design wavelengths correctly. Performance of the WMDPE is evaluated by
      computer simulations on the uniformity error, the light efficiency, and the
      contrast. On the basis of the results, the characteristics of the WMDPE's are
      discussed in terms of various conditions of fabrication and usage.

PMID- 11336212
TI  - Numerical feasibility study of the fabrication of subwavelength structure by mask
      lithography.
AB  - Electromagnetic diffraction of a light wave by a single aperture of subwavelength
      width and subsequent propagation in a lossy medium are numerically investigated.
      This diffraction problem simulates exposure of a resist with an amplitude mask.
      It is found that there is the possibility of fabricating a lambda/2 structure on
      a resist of lambda/4 thickness, where lambda is the wavelength of the exposing
      light in vacuum, by conventional contact or by proximity lithography. It is also
      found that an air gap between a mask and a resist of up to lambda/2 does not have
      a significant effect on resolution. This approach permits easy and cost-effective
      fabrication of subwavelength structures and leads to wide availability of
      diffractive optical elements in the nonscalar domain.

PMID- 11336213
TI  - Electromagnetic wave scattering from conducting self-affine surfaces: an analytic
      and numerical study.
AB  - We derive an analytical expression for the scattering of an s-polarized plane
      wave from a perfectly conducting self-affine one-dimensional surface in the
      framework of the Kirchhoff approximation. We show that most of the results can be
      recovered by means of a scaling analysis. We identify the typical slope taken
      over one wavelength as the relevant parameter controlling the scattering process.
      We compare our predictions with direct numerical simulations performed on
      surfaces of varying roughness parameters and confirm the broad range of
      applicability of our description up to very large roughness. Finally we verify
      that a nonzero electrical resistivity, provided that it is small, does not
      invalidate our results.

PMID- 11336214
TI  - Geometrical renormalization approach to calculating optical properties of fractal
      carbonaceous soot.
AB  - We develop a theoretical approach to calculating optical properties of
      carbonaceous soot in the long-wavelength limit. Our method is based on
      geometrical renormalization of clusters; it avoids both the inaccuracy of the
      dipole approximation in its pure form and the numerical complexity of rigorous
      direct methods of solving the EM boundary problem. The results are verified by
      comparison with the experimental measurements for specific extinction of diesel
      soot in the spectral region from 0.488 microm to 0.857 cm that were performed by
      Bruce et al. [Appl. Opt. 30, 1537 (1991)]. The theory leads to analytical
      expressions that are applicable to different soots, with various geometrical
      properties and optical constants. We show that the functional form of the long
      wavelength asymptote of the specific extinction can depend critically on a
      parameter characterizing the sample geometry, and we identify the critical value
      of this parameter.

PMID- 11336215
TI  - Nonreciprocal effects in the double passage of light through a random diffuser
      and a birefringent crystal.
AB  - We present a theoretical and experimental study of the scattering of light by
      double passage through a system that consists of a strong diffuser, a piece of
      birefringent crystal, and a plane mirror. We show that this arrangement can
      produce not only enhanced backscattering and satellite peaks but also satellite
      dips in the angular distribution of the mean intensity. The experiments are in
      agreement with theoretical results based on scalar diffraction theory in the
      paraxial approximation.

PMID- 11336216
TI  - Using rays better. I. Theory for smoothly varying media.
AB  - We present a method for computing ray-based approximations to optical fields that
      not only offers unprecedented accuracy but is also accompanied by accessible
      error estimates. The basic elements of propagation through smooth media,
      refraction and reflection at interfaces, and diffraction by obstacles give the
      foundations for the new framework, and the first of these is treated here. The
      key in each case is that the wave field and any relevant derivatives are
      expressed consistently as a superposition of delocalized ray contributions. In
      this way, the mysteries surrounding the sometimes perplexing tenaciousness of ray
      based estimates are clearly resolved. Further, an essential degree of freedom in
      this approach offers an attractive resolution of part of the apparent conflict of
      particle/wave duality.

PMID- 11336217
TI  - Using rays better. II. Ray families to match prescribed wave fields.
AB  - A key step in any ray-based method for propagating waves is the choice of a
      family of rays to be associated with the initial wave field. We develop some
      basic prescriptions for constructing initial ray families to match two particular
      types of waves. Various Gaussian and Bessel beams are separately given special
      treatment because of their general interest. These ideas are directly useful for
      a newly developed method for ray-based wave modeling. The new method expresses
      the wave as a superposition of ray contributions that is independent of the width
      of the field element associated with each ray. This insensitivity is investigated
      here even when the elemental width varies from ray to ray. The results increase
      the applicability of the new wave-modeling scheme.

PMID- 11336218
TI  - Resonant scattering and mode coupling in two-dimensional textured planar
      waveguides.
AB  - A heuristic formalism is developed for efficiently determining the specular
      reflectivity spectrum of two-dimensionally textured planar waveguides. The
      formalism is based on a Green's function approach wherein the electric fields are
      assumed to vary little over the thickness of the textured part of the waveguide.
      Its accuracy, when the thickness of the textured region is much smaller than the
      wavelength of relevant radiation, is verified by comparison with a much less
      efficient, exact finite difference solution of Maxwell's equations. In addition
      to its numerical efficiency, the formalism provides an intuitive explanation of
      Fano-like features evident in the specular reflectivity spectrum when the
      incident radiation is phase matched to excite leaky electromagnetic modes
      attached to the waveguide. By associating various Fourier components of the
      scattered field with bare slab modes, the dispersion, unique polarization
      properties, and lifetimes of these Fano-like features are explained in terms of
      photonic eigenmodes that reveal the renormalization of the slab modes due to
      interaction with the two-dimensional grating. An application of the formalism, in
      the analysis of polarization-insensitive notch filters, is also discussed.

PMID- 11336219
TI  - Theory and measurement of Young's modulus radial profiles of bent single-mode
      optical fibers with the multiple-beam interference technique.
AB  - Multiple-beam Fizeau fringes in transmission have been applied to the study of
      the nonlinear stress-strain relationship due to bending in the cladding of single
      mode optical fibers. The present study yields a relation between the variation of
      refractive indices of bent single-mode fibers, represented by the fringe shift,
      and the nonlinear radial change of Young's modulus along the fiber cross section.
      Experimentally, the study confirms the nonlinear asymmetric stress-strain
      relation across the fiber cross section. This relation is due to the asymmetric
      distribution of the compression and tensile stresses over the fiber cross section
      rather than to the shift in the centroid (neutral axis).

PMID- 11336220
TI  - Fiber mode conversion with tilted gratings in an optical fiber.
AB  - The mode coupling in double-sided tilted gratings between the LP01 and LP11 modes
      is analyzed for three different excitation conditions. It is found that a number
      of modes, including various LP11q modes with different polarization states and
      TE01, TM01, and HE21 modes, can be formed through the mode conversion process in
      the gratings and with a linear combination of four different LP11 modes.
      Efficient single-sided and double-sided tilted gratings are demonstrated. The
      tilted gratings presented exhibit LP01-to-LP11 mode coupling over a spectral
      width as wide as 160 nm. The transmission spectra of the tilted fiber gratings
      agree well with the spectrum predicted by the coupled-mode analysis.

PMID- 11336221
TI  - Characterization of alpha-phase soft proton-exchanged LiNbO3 optical waveguides.
AB  - Waveguides in LiNbO3 are realized by a soft proton exchange (SPE) process with
      use of a melt of stearic acid highly diluted by lithium stearate. No phase
      transitions are formed when alpha-phase waveguides are obtained by SPE. The alpha
      phase presents the same crystalline structure as that of pure LiNbO3 crystal, and
      it maintains the excellent nonlinear and electro-optical properties of the bulk
      material. The kinetics of the SPE method is studied by the use of secondary-ion
      mass spectrometry and prism-coupling techniques. The hydrogen effective diffusion
      coefficient as well as the self-diffusion coefficients of H+ and Li+ ions are
      determined as a function of the proton-exchange temperature for X-cut LiNbO3.

PMID- 11336222
TI  - Luminance spatial scale facilitates stereoscopic depth segmentation.
AB  - Are differences in luminance spatial frequency between surfaces that overlap in
      depth useful for surface segmentation? We examined this question, using a novel
      stimulus termed a dual-surface disparity grating. The dual-surface grating was
      made from Gabor micropatterns and consisted of two superimposed sinusoidal
      disparity gratings of identical disparity-modulation spatial frequency and
      orientation but of opposite spatial phase. Corrugation amplitude thresholds for
      discrimination of the orientation of the dual-surface grating were obtained as a
      function of the difference in Gabor (luminance) spatial frequency between the two
      surfaces. When the Gabor micropatterns on the two surfaces were identical in
      spatial frequency, thresholds were very high and in some instances impossible to
      obtain. However, with as little as a 1-octave difference in spatial frequency
      between the surfaces, thresholds fell sharply to near-asymptotic levels. The fall
      in thresholds paralleled a change in the appearance of the stimulus from one of
      irregular depth to stereo transparency. The most parsimonious explanation for
      this finding is that the introduction of a between-surface luminance spatial
      frequency difference reduces the number of spurious cross-surface binocular
      matches, thus helping to reveal the three-dimensional structure of the stimulus.

PMID- 11336223
TI  - Expressed sequence tags for the chicken genome from a normalized 10-day-old White
      Leghorn whole embryo cDNA library: 1. DNA sequence characterization and linkage
      analysis.
AB  - Expressed sequence tags (ESTs) provide a rapid and reliable method for gene
      discovery as well as a resource for the large-scale analysis of gene expression
      of known and unknown genes. Here we describe a normalized cDNA library developed
      from a 10-day-old White Leghorn chicken whole embryo. The utility of the library
      was evaluated by partial sequencing of 99 randomly selected insert-containing
      clones and the analysis of EST-targeted genomic regions for single nucleotide
      polymorphisms (SNPs) in the East Lansing chicken reference DNA mapping panel.
      Using stringent match criteria of percent identity of 80 or higher across a
      length of 50 or more bases, 46 ESTs matched database sequences including
      previously reported Gallus gallus genes. Thirty-seven of the 50 primer pairs
      developed from 50 unique ESTs amplified a single fragment. The size of the 37
      amplicons ranged from 276 to 693 bp for a total of 17,508 and an average of 473.
      About 70% of the SNPs detected were either G-->A or C-->T transition. The number
      of SNPs detected within the amplicons from EST-targeted genomic regions ranged
      from 0 to 4 for a total of 65 and a frequency of about 1 every 470 bases. About
      35% of the amplicons contained only 1 SNP, while 19% had 4 SNPs. Using the SNPs
      that were informative in the East Lansing reference panel, 17 ESTs were mapped on
      the East Lansing chicken genetic map. The ESTs described, as well as the
      nucleotide variants identified within the EST-targeted genomic regions, represent
      significant resources for genome analysis in the chicken.

PMID- 11336224
TI  - Composite interval mapping reveals a major locus influencing embryonic
      development rate in rainbow trout (Oncorhynchus mykiss).
AB  - Little is known about the genetics controlling the rate of embryonic development
      in salmonids, despite the fact that this trait plays an important role in the
      life history of wild and cultured stocks. We investigated the genetics of
      embryonic development rate by performing an analysis of quantitative trait loci
      (QTL) on two families of androgenetically derived doubled haploid rainbow trout
      produced from a hybrid of two clonal lines with divergent embryonic development
      rates. A total of 170 doubled haploid individuals were genotyped at 222 marker
      loci [219 amplified fragment length polymorphism (AFLP) markers, 2
      microsatellites, and p53]. A genetic linkage analysis resulted in a map
      consisting of 27 linkage groups with 21 of the markers remaining unlinked at a
      minimum LOD of 3.0 and maximum theta of 0.40. Eight of these linkage groups were
      matched to published rainbow trout linkage groups. Composite interval mapping
      (CIM) revealed evidence for two QTL influencing time to hatch, and suggestive
      evidence for a third. These QTL accounted for a total of 24.6% of the variation
      in time to hatch. One of these QTL had a large effect on development rate,
      especially in one family of doubled haploids, in which it explained 25.6% of the
      variance in time to hatch. QTL influencing embryonic length and weight at the
      commencement of exogenous feeding were also identified. The QTL with the
      strongest effect on embryonic length (lenR13) mapped to the same position as the
      QTL with the strongest effect on time to hatch (tthR13), suggesting a single QTL
      may have a pleiotropic effect on both these traits. These results suggest that
      the use of clonal lines with a doubled haploid crossing design is an effective
      way of analyzing the genetic basis of complex traits in salmonids.

PMID- 11336225
TI  - Developmental stability in house mice heterozygous for single Robertsonian
      fusions.
AB  - Fluctuating asymmetry (FA) of tooth traits has been reported to be increased in
      Down syndrome patients as well as hybrids between chromosomal races of the house
      mouse differing in several Robertsonian (Rb) fusions. Developmental stability,
      assessed by FA, is thus thought to be impaired by spontaneous chromosomal
      abnormality or by chromosomal heterozygosity. Although the effect of a single
      fusion on developmental stability could theoretically be expected, it has never
      been documented. Crosses involving two chromosomal races of the house mouse
      diverging for one Rb fusion were performed to assess developmental stability in
      parental homozygous races as well as in their hybrids. Moreover, the occurrence
      of a spontaneous chromosomal mutation (WART type-b) allowed us to study the
      instantaneous effect of such a translocation on developmental stability. No
      difference in fluctuating asymmetry levels was detected among the groups
      considered in this study. This result suggested that a single stable or
      spontaneous balanced structural rearrangement did not inherently disturb
      developmental stability. In addition, the differential effect on developmental
      stability of one versus many heterozygous Rb fusions highlights the role of their
      quantitative accumulation in the disruption of coadaptation in chromosomal
      hybrids.

PMID- 11336226
TI  - Age-specific fitness components in hybrid females of Drosophila pseudoobscura and
      D. persimilis.
AB  - Most models of hybridization assume that hybrids are less fit than their parental
      taxa. In contrast, some researchers have explored the possibility that hybrid
      individuals may actually have higher fitness and so play an important role in the
      generation of new species or adaptations. By estimating age-specific fitness
      components, we can determine not only how hybrid fitness differs from parental
      taxa, but also whether the fitness of hybrids relative to parental taxa changes
      with age. Here we describe an analysis of age-specific fitness traits in two
      species of Drosophila, D. pseudoobscura and D. persimilis, and their F1 hybrids.
      At early ages, hybrid females lay as many eggs as parental individuals, on
      average, but produce far fewer offspring. By late ages, in contrast, parental
      taxa show a steep decline in production not seen in hybrids, such that hybrids
      produce more offspring, on average, than parental taxa. Furthermore, egg-adult
      survival in hybrids is negatively correlated with egg density, whereas these
      traits are only weakly correlated in parental taxa. The results are limited
      somewhat by the fact that we analyze only two strains, and that these may be
      partially inbred. Nonetheless, the results are certainly illustrative, pointing
      out not only that at least some hybrid individuals may be as fit or fitter than
      parental taxa, but also that the difference between hybrids and parental taxa
      varies with age.

PMID- 11336227
TI  - Identification of wild and cultivated sunflower for breeding purposes by AFLP
      markers.
AB  - Amplified fragment length polymorphisms (AFLPs) represent one of the most
      powerful polymerase chain reaction (PCR)-based markers which enables one to
      discriminate single plants by DNA analysis. To date this technique has only been
      applied in cultivated sunflower to detect genetic diversity among oilseed inbred
      lines. In this article we report the use of AFLP markers to investigate the level
      of diversity within and between populations of Helianthus argophyllus collected
      in the Maputo area, Mozambique, both for taxonomic and breeding purposes. Three
      primer combinations gave the best results with 92 polymorphic fragments and were
      able to discriminate these wild endemic populations from H. annuus and from one
      of its interspecific hybrids. Most of the variation (71%) observed was within
      population, and the dendrogram based on shared fragments did not divide the H.
      argophyllus genotypes into distinct groups resembling different populations.
      Moreover the hybrid genotypes formed distinguishable subgroups with the
      cultivated sunflower genotype, confirming the suitability of this technique for
      taxonomic and phylogenetic studies. From a breeding point of view, although the
      12 populations of H. argophyllus represent a new valuable genetic resource, only
      two of them possessed most of the variation observed, suggesting that they can be
      the most promising material for crossing with cultivated sunflower.

PMID- 11336228
TI  - Genetic analysis of mutations at loci controlling leaf form in cowpea (Vigna
      unguiculata.
AB  - Mutations affecting leaflet number and shape occurred at high frequencies in some
      cowpea crosses. Mutant plants were nonpetiolate and unifoliolate as opposed to
      normal plants which were petiolate and trifoliolate. Two types of unifoliolate
      mutants were distinguishable on the basis of leaf shape which was ovate in one
      mutant and orbicular in the other. The nonpetiolate and the unifoliolate traits
      in the two mutants are each controlled by single recessive genes, but the genes
      controlling the traits in the different mutants were nonallelic. The orbicular
      leaf shape was also under the control of a single recessive gene. In the F2 and
      subsequent generations of the cross IBS 2497 x IBS 2625, orbicular-shaped
      unifoliolate leaf mutants were regularly produced, although the two parents
      involved in the cross were both trifoliolate. Linkage tests showed that the genes
      pt-1 for nonpetiolate trait, un-2 for unifoliolate leaf, and orb for orbicular
      leaf shape in one of the mutants were located on the same chromosome, while the
      genes pt-3 and un-3 in the other were also linked on a different chromosome. The
      results of this study provide further evidence indicating the involvement of
      transposable elements in the mutations observed in the cowpea lines used in this
      study.

PMID- 11336229
TI  - Inheritance and allelism tests of Raiden soybean for resistance to soybean mosaic
      virus.
AB  - The gene symbol Rsv2 was previously assigned to the gene in the soybean [Glycine
      max (L.) Merr.] line OX670 for resistance to soybean mosaic virus (SMV). The Rsv2
      gene was reported to be derived from the Raiden soybean (PI 360844) and to be
      independent of Rsv1. Accumulated data from our genetic experiments were in
      disagreement with this conclusion. In this study, Raiden and L88-8431, a Williams
      BC5 isoline with SMV resistance derived from Raiden, were crossed with two SMV
      susceptible cultivars to investigate the mode of inheritance of SMV resistance in
      Raiden. They were also crossed with five resistant cultivars to examine the
      allelomorphic relationships of the Raiden gene with other reported genes at the
      Rsv1 locus. F1 plants, F2 populations, and F2-derived F3 (F2:3) lines were tested
      with SMV strains G1 or G7 in the greenhouse or in the field. The individual plant
      reactions were classified as resistant (R, symptomless), necrotic (N, systemic
      necrosis), or susceptible (S, mosaic). The F2 populations from R x S crosses
      segregated in a ratio of 3 (R + N):1 S and the F2:3 lines from Lee 68 (S) x
      Raiden (R) exhibited a segregation pattern of 1 (all R):2 segregating:1 (all S).
      The F2 populations and F2:3 progenies from all R x R crosses did not show any
      segregation for susceptibility. These results demonstrate that the resistance to
      SMV in Raiden and L88-8431 is controlled by a single dominant gene and the gene
      is allelic to Rsv1. The heterozygous plants from R x S and R x N crosses
      exhibited systemic necrosis when inoculated with SMV G7, indicating a partial
      dominance nature of the resistance gene. Raiden and L88-8431 are both resistant
      to SMV G1-G4 and G7, but necrotic to G5, G6, and G7A. Since the resistance gene
      in Raiden is clearly an allele at the Rsv1 locus and it exhibits a unique
      reaction to the SMV strain groups, assignment of a new gene symbol, Rsv1-r, to
      replace Rsv2 would seem appropriate. Further research is ongoing to investigate
      the possible existence of the Rsv2 locus in OX670 and its relatives.

PMID- 11336230
TI  - Anther culture-derived regenerants of durum wheat and their cytological
      characterization.
AB  - Anther culture is being increasingly used in cereal crop improvement both as a
      source of haploids and for inducing new genetic variation. We studied the
      androgenetic ability and regenerability of 10 cultivars of durum wheat (Triticum
      turgidum L., 2n = 4x = 28; AABB), using three different growth conditions and
      four media. From a total of 86,400 anthers cultured, 324 plants were obtained:
      248 green and 76 albino. Genotype, growth condition, and media significantly
      affected anther response and callus production; interactions were also
      significant. Green plant regeneration was influenced significantly by genotype
      and growth condition, as well as by genotype and growth condition interactions.
      Albino plant regeneration was significantly affected only by growth condition.
      Regenerants showed gametoclonal/somaclonal variation. Differences in morphology,
      growth habit, adult plant height, spike size, and development of spikes at nodes
      were observed. Mitotic and meiotic chromosomes were studied by conventional
      staining and fluorescent genomic in situ hybridization techniques. Chromosome
      numbers of the regenerants ranged from 14 to 70. All 76 haploid plantlets (2n =
      2x = 14; AB) were albino. Some of the 28-chromosome regenerants were also albino.
      Chromosome number in the green plantlets ranged from 28 to 70. Chromosome number
      also varied in regenerants originating from the same callus. Both intergenomic
      and intragenomic multivalents were observed. An interesting feature was the
      preferential multiplication of B-genome chromosomes, which formed multivalents
      (trivalents, quadrivalents, and hexavalents). We observed several chromosomal
      abnormalities, which seemed to increase with the level of polyploidy.
      Translocations, dicentric chromosomes, chromatid exchanges, and Robertsonian
      translocations involving the A- and B-genome chromosomes were observed.
      Chromosome breakages resulting in centric and acentric fragments, and
      telocentrics were observed. Chromosome multiplication and structural aberrations
      induced during culture may constitute the bases of gametoclonal and somaclonal
      variations.

PMID- 11336231
TI  - Allozyme variation of Cyclobalanopsis championii (Fagaceae), a narrowly
      distributed species in southern Taiwan.
AB  - Allozyme genetic variability in five natural populations of Cyclobalanopsis
      championii (Fagaceae) in Taiwan was investigated using 12 loci from 9 enzyme
      systems. The average values of parameters describing within-population variation,
      expected heterozygosity (He = 0.151), the percentage of polymorphic loci per
      individual (P = 50%), the average number of alleles per locus (A = 1.7),
      effective number of alleles per locus (Ae = 1.25), and the average number of
      alleles per polymorphic loci (AP = 2.2) are comparable to those of other long
      lived woody plants. The overall fixation index (Fis = 0.208) indicates a
      significant deficiency of heterozygotes at the population level. Allelic
      frequency deviation from Hardy-Weinberg equilibrium was found for different loci
      in different populations. An exact test for population differentiation using the
      Tools for Population Genetic Analyses program also indicates that allelic
      frequencies among populations are significantly different (P < .001). Among
      population variation, Gst, accounted for 9.2% of the total heterozygosity. The
      population at Shouchia and the southernmost population Nanjenshan had higher
      inbreeding coefficients (0.177 and 0.153, respectively) than did the northern
      populations. Genetic drift is supported by the observations of the variance
      components of linkage disequilibrium and a large proportion of loci in Nanjenshan
      and Shouchia that show pairwise locus disequilibrium. We believe continuous
      genetic drift in the southern populations will increase genetic divergence among
      populations of C. championii in Taiwan. Significant correlation was found between
      elevation and expected heterozygosity. We therefore inferred that temperature is
      the most important ecological factor to influence the genetic diversity of C.
      championii.

PMID- 11336232
TI  - Low microsatellite variation in laboratory gerbrils.
AB  - The Mongolian gerbil has become a model organism of increasing importance for the
      understanding of aging, epilepsy, the process of domestication or sociobiological
      questions. We report the development and characterization of the first nine
      polymorphic dinucleotide repeat loci in this species. Average observed
      heterozygosity and allele number of laboratory animals measured 0.136 (SE = +/
      0.065) and 1.78 (SE = +/-0.278) compared to 0.761 (SE = +/-0.025) and 9.2 (SE =
      +/-0.57) found for a reference group of wild gerbils. The extreme low genetic
      variation observed in laboratory animals is caused by several severe population
      size bottlenecks due to the initial founder event and the later establishment of
      subpopulations. Reduced levels of allelic polymorphism in experimental animals
      hamper genetic mapping or parental studies. Therefore experiments relying on
      kinship analyses have to be carried out on wild animals. Estimates of genetic
      identity and parental exclusion were calculated as Pid = 2.8 x 10(-12) and Pex >
      0.999 in wild gerbils. Laboratory gerbil strains show the expected high degree of
      genetic similarity. However, significant allele frequency differences (P < .001)
      between American and European gerbils at some microsatellite loci may still allow
      discrimination between breeding lines.

PMID- 11336233
TI  - A second acromelanistic allelomorph at the albino locus of the Mongolian gerbil
      (Meriones unguiculatus).
AB  - A new autosomal recessive coat color mutant in the Mongolian gerbil (Meriones
      unguiculatus) is described: chinchilla medium (symbol c(chm)). The mutant has
      typical acromelanistic features similar to those of several acromelanistic c
      locus mutants of other species of mammals. Previously a more severe form of
      acromelanism (c(h)c(h)) has been described in the Mongolian gerbil. The new
      allele shows to be allelic with this form. On a nonagouti background compound
      heterozygotes (aac(chm)c(h)) show an intermediate phenotype that is very similar
      to that of the Siamese mouse (Mus musculus) and rat (Rattus norvegicus).
      Homozygotes (aac(chm)c(chm)) display a very dark acromelanistic phenotype
      reminiscent of that of the sable rabbit (Oryctolagus cuniculus). The gray
      phenotype (gg) in the Mongolian gerbil resembles the albino locus phenotype
      chinchilla (c(ch)c(ch)) in mice. We show that the new mutant is not allelic with
      gray. Fertility and viability of the new mutant are within normal range.

PMID- 11336234
TI  - A linkage map for CRINKLED PETAL: a homeotic gene of Clarkia tembloriensis
      (Onagraceae).
AB  - Homeotic mutations in flowers lead to the development of floral organs in
      abnormal locations. In most laboratory-induced examples of this type of mutation,
      two adjacent whorls of organs are affected, resulting in two whorls of abnormal
      organ formation. However, the crinkled petal mutant of Clarkia tembloriensis is
      interesting because it is a naturally occurring mutation and it affects only the
      second whorl of organs, producing sepaloid petals. In this study one wild-type
      population (Cantua Creek-2) and one crinkled petal mutant population (Red Rocks)
      were compared using 181 different primers in random amplified polymorphic DNA
      (RAPD) analysis. Bulk DNA from each parent population and their subsequent
      crosses were used to compare the genetic differences between the two populations
      and to search for molecular markers linked with the CRINKLED PETAL locus. A
      linkage map was developed for the CRINKLED PETAL gene, and markers were
      discovered which flanked both sides of the locus.

PMID- 11336235
TI  - Production of wheat doubled haploids by pollination with Job's tears (Coix
      lachryma-jobi. L.).
AB  - Wheat (Triticum aestivum L.) haploids were produced by crossing with Job's tears
      (Coix lachryma-jobi L.) as the pollen parent. Pollination was followed by 2,4-D
      treatment, detached tiller culture, and embryo culture, as described for maize
      pollination. The frequency of embryo formation was similar to that obtained by
      crossing wheat with maize pollen. Job's tears is a perennial plant which forms
      several stalks and its pollen can be collected throughout the year when the plant
      is maintained in a controlled environment. Our results indicate that Job's tears
      can be used as the pollen parent for wheat crosses for haploid production without
      requiring synchronization of flowering dates.

PMID- 11336236
TI  - A recessive allele inhibiting saponin synthesis in two lines of Bolivian quinoa
      (Chenopodium quinoa Willd.).
AB  - Quinoa cultivars currently grown in North America and Europe require removal of
      bitter-tasting saponins from the grain prior to human consumption. This need for
      postharvest processing is a barrier to expanding production of the crop outside
      its Andean area of origin. Grain saponin content in quinoa shows continuous
      variation and is considered to be a quantitative trait. However, segregation for
      the presence or absence of grain saponin in F2 generations derived from crosses
      between high- and low-saponin parents indicates a major gene effect, with plants
      homozygous for a recessive allele spl having no detectable grain saponin.
      Variation in saponin levels among F2 plants with detectable grain saponin was
      consistent with polygenic inheritance. It appears that grain saponin level in
      quinoa is both qualitatively and quantitatively controlled, with saponin
      production requiring at least one dominant allele at the Sp locus and the amount
      of grain saponin being determined by an unknown number of additional quantitative
      loci. Introgression of sp1 into day-neutral lines will facilitate the development
      of short-season "sweet" quinoa cultivars which do not require postharvest
      processing to remove grain saponin.

PMID- 11336237
TI  - Parental effects in the inheritance of nonnodulation in peanut.
AB  - A nonnodulating line (M4-2) and three normal nodulating lines (UF 487A, PI
      262090, and Florunner) of peanut (Arachis hypogaea L.) were crossed in full
      diallel to investigate the inheritance of nodulation. Data from F1, F2, F3,
      F1BC1, and F2BC1 generations indicated that three genes control nodulation at
      three independent loci, with nodulation being a product of two genes and
      inhibited by a third gene when it is dominant and the others are homozygous
      recessive. A genetic model has been proposed that describes the nonnodulated
      genotypes as n1n1n2n2N3N3 or n1n1n2n2N3n3 and all other genotypes as normally
      nodulated except n1n1N2n2N3-, which has reduced nodulation when the n1n2N3 male
      gamete unites with the n1N2- female gamete or when the n1n2n3 male gamete unites
      with the n1N2N3 female gamete.

PMID- 11336238
TI  - Genetic and linkage analysis of cleistogamy in soybean.
AB  - Early maturing cultivars of soybean [Glycine max (L.) Merr.] native to the shores
      of the Sea of Okhotsk (Sakhalin and Kuril Islands) and eastern Hokkaido (northern
      Japan) have been used in breeding for chilling tolerance. These cultivars have a
      strong tendency to produce cleistogamous flowers throughout their blooming
      period. This study was conducted to determine the genetic basis of cleistogamy in
      an early maturing cultivar, Karafuto-1, introduced from Sakhalin. Genetic
      analysis was performed using F1 plants, the F2 population, and 50 F3 families
      produced by crossing between Karafuto-1 and a chasmogamous cultivar, Toyosuzu. F2
      plants had chasmogamous flowers, indicating that chasmogamy was dominant to
      cleistogamy. Analysis of F2 populations and F3 families generated segregation
      data that was close to a two-gene model with epistatic interactions, although a
      portion of the pooled F3 data on the frequency of chasmogamous segregants from
      cleistogamous families significantly deviated from the model. The results
      suggested that a minimum of two genes with epistatic effects were involved in the
      genetic control of cleistogamy. Furthermore, cleistogamy was associated with
      early flowering in the F2 and F3 populations. A gene for cleistogamy was linked
      to one of the recessive genes responsible for insensitivity to incandescent long
      daylength.

PMID- 11336240
TI  - MSTRAT: an algorithm for building germ plasm core collections by maximizing
      allelic or phenotypic richness.

PMID- 11336239
TI  - Genetic distinctiveness of endangered dwarf blue sheep (Pseudois nayaur
      schaeferi): evidence from mitochondrial control region and Y-linked ZFY intron
      sequences.
AB  - To elucidate the controversial systematic relationship of blue sheep (Pseudois
      nayaur) and endangered dwarf blue sheep, we sequenced part of the mtDNA control
      region and Y-linked ZFY intron, and carried out phylogenetic analyses.
      Mitochondrial results revealed that the dwarf blue sheep is a strongly supported
      monophyletic group, with an average of 12.21% sequence divergence from the blue
      sheep. This is the first genetic evidence for the distinctness of the dwarf blue
      sheep. ZFY intron results showed an average of 0.51% sequence divergence, and one
      shared haplotype between the dwarf blue sheep and blue sheep. By analyzing an
      expanded data set that incorporated ZFY intron sequences of two additional Ovis
      (sheep) species-O. nivicola and O. ammon--we demonstrated that ZFY intron
      provides good resolution at the species and genus levels. The ZFY intron sequence
      divergence between dwarf blue sheep and blue sheep was comparable to that within
      the two Ovis species. Moreover, we found intraspecific sequence variation in ZFY
      intron for all three species examined. We propose that dwarf blue sheep be
      designated as a subspecies of blue sheep, P. n. schaeferi.

PMID- 11336241
TI  - Biomedical and psychosocial determinants of psychiatric morbidity among
      postoperative ambulatory breast cancer patients.
AB  - There has been much interest in the psychosocial issues faced by breast cancer
      patients because of the high prevalence of the disease and the severe
      psychological impact of the cancer itself, as well as its treatment. The
      objective of our study was to investigate the determinants of psychiatric
      morbidity among postoperative ambulatory breast cancer patients. The variables
      examined included the patients' biomedical characteristics, demographic
      characteristics, current concerns, coping responses and social support factors.
      Patients completed the Hospital Anxiety and Depression Scale (HADS) and the
      Mental Adjustment to Cancer scale (MAC scale), and information pertaining to
      demographic variables, current concerns and social support factors was obtained
      by a specially designed questionnaire. Available data were obtained from 148
      randomly selected postoperative ambulatory breast cancer patients. The prevalence
      of psychiatric morbidity (including clinical anxiety and depression) evaluated by
      using the HADS cut-off point was 23%. The results of univariate analyses
      indicated that pain, dyspnea, having children with health problems, various other
      concerns (about children, other family members, the patients' own health and
      future treatment) and poor coping responses (low fighting spirit, high anxious
      preoccupation, high fatalism and high helplessness/hopelessness) were significant
      determinants of the patients' psychiatric morbidity. Additionally, in the
      logistic regression analysis, having children with health problems and having a
      low fighting spirit and a high helplessness/hopelessness were final significant
      determinants. Postoperative ambulatory breast cancer patients with these problems
      should be given careful attention, and psychosocial intervention may be
      beneficial for them.

PMID- 11336242
TI  - Angiogenesis and blood vessel invasion as prognostic indicators for node-negative
      breast cancer.
AB  - This study was undertaken to determine the value of angiogenesis and blood vessel
      invasion (BVI) using both Factor VIII-related antigen and elastica van Gieson
      staining in predicting 20-year relapse-free survival (RFS) and 20-year overall
      survival (OS) rates in Japanese patients with node-negative breast cancer. Two
      hundred and sixty patients were studied. We investigated nine factors, including
      angiogenesis (average microvessel count (AMC)), BVI, proliferating cell nuclear
      antigen (PCNA), p53, c-erbB-2, clinical tumor size (T), histological grade, tumor
      necrosis, and lymphatic vessel invasion (LVI). Twenty-five patients (9.6%) had
      recurrence and 17 patients (6.5%) died of breast cancer. Univariate analysis
      showed that BVI, AMC, T, histological grade, PCNA, p53, and tumor necrosis were
      significantly predictive of RFS or OS. Multivariate analysis showed that AMC,
      BVI, and T were significant independent factors for RFS or OS. Moreover, the
      combination of AMC/BVI was an especially significant factor for RFS or OS (P <
      0.0001, P = 0.0003, respectively). When stratified by T, a significant impact of
      AMC or BVI on RFS was seen in patients with T1, T2, and T3 carcinomas.
      Multivariate analysis in patients with T2 carcinoma showed that both AMC and BVI
      were significant independent factors for RFS (P = 0.0231, P = 0.0388,
      respectively) and OS (P = 0.0331 and P = 0.0479, respectively). AMC, BVI, and T
      were independent prognostic indicators. As the combined impact of AMC/BVI is
      especially strong, AMC/BVI is useful in selecting high-risk node-negative breast
      cancer patients who may be eligible to receive aggressive adjuvant chemotherapy.

PMID- 11336243
TI  - Premenopausal status accelerates relapse in node positive breast cancer:
      hypothesis links angiogenesis, screening controversy.
AB  - Much attention has been given to determining the benefit of mammographic
      screening to reduce breast cancer mortality. Eight randomized clinical trials
      have been conducted in four countries: the US, Canada, Scotland and Sweden.
      Trials report an early and stable 30% reduction in breast cancer mortality for
      women aged 50-59. For women under 50, unexpectedly, the early years of screening
      produce a disadvantage to the screened population. Only in later years does an
      advantage appear. To help understand this, we studied relapse patterns using a
      breast cancer database of 1,173 pre- and postmenopausal, node negative and
      positive patients treated with surgery only and having 16-20 years of follow-up.
      This approach is relevant since at least five of the eight screening trials began
      before the widespread use of adjuvant chemotherapy in the 1980s. Surgical cure
      rates were independent of menopausal status. However, a major difference in early
      relapse rate was found. In premenopausal and node positive patients, 27% of all
      distant relapses occurred within the first 10 months following resection. This is
      twice the early relapse frequency of any other clinical group. Using computer
      simulation, we interpret that these early relapses probably result from a
      disadvantage induced at surgery. A disinhibition or surgery/wounding induced
      angiogenic surge might be responsible. Disinhibition is known to occur in animal
      models such as Lewis lung where lung metastases are avascular and dormant until
      the primary is removed. Sudden outgrowth of tumor after wounding has been
      observed for a century. According to the simulation, in breast cancer this
      induction apparently accelerates inevitable relapses by a median of two years.
      This is offset in later years with a balancing reduction in relapses. These data
      suggest that the angiogenic switch may be upregulated more frequently among
      premenopausal women, perhaps depending upon the sex hormones. The acceleration
      would cause 0.11 deaths per 1,000 screened aged 40-49 subjects in years 2-3, a
      value comparable to the early year excess mortality in trials of a significant
      0.15 deaths per 1,000 subjects. Equal screening advantage is predicted for node
      negative (but not node positive) pre- and postmenopausal patients. The
      acceleration of relapse after surgery may explain the paradoxical effect of
      mammographic screening for women under 50.

PMID- 11336244
TI  - Genetic alterations of the p14ARF -hdm2-p53 regulatory pathway in breast
      carcinoma.
AB  - TP53 is the most commonly mutated tumor suppressor gene in human cancers. The
      amplification and overexpression of HDM2 plays a role in tumorigenesis via
      inactivation of p53-dependent cell cycle arrest. p14ARF, an alternate transcript
      of the INK4A tumor suppressor locus, prevents hdm2-induced transcriptional
      silencing of p53 by binding hdm2. The role of this p14ARF-hdm2-p53 regulatory
      pathway in breast carcinoma is unknown. We hypothesized that p14ARF mutations and
      HDM2 gene amplification may be alternative mechanisms of p53 inactivation in
      breast cancer. Mutational analysis of TP53 (exons 5-9) and exon 1beta of pl4ARF
      was performed by PCR-SSCP and putative mutations were confirmed by sequencing.
      p14ARF mRNA expression was evaluated by RT-PCR and the presence of HDM2 gene
      amplification by differential PCR. Among the cell lines, 7/14 (50%) harbored TP53
      mutations and 2/14 (14%) had a deletion ofp14ARF exon 1beta with no detectable
      p14ARF mRNA. None demonstrated HDM2 gene amplification. TP53 mutations were
      identified in 7/36 (19%) breast tumors and HDM2 amplification in 2/30 (7%)
      tumors. All the tumors contained an intact p14ARF exon 1beta with corresponding
      expression of the mRNA. Alterations in the various components of this regulatory
      pathway were identified in nine (64%) cell lines and 25% of the 36 breast cancers
      with TP53 mutation being the predominant aberration. Although p14ARF mutations
      and HDM2 gene amplification appear to be uncommon events in breast carcinoma,
      deregulation of this pathway may occur via alternative mechanisms in breast
      carcinogenesis.

PMID- 11336245
TI  - Health system costs of metastatic breast cancer.
AB  - To assess the costs of treating patients with incurable breast cancer, all health
      system costs during the interval from diagnosis of first recurrence or metastasis
      until death for 75 female subjects randomly selected from those known to have
      died of breast cancer in British Columbia, Canada between July 1, 1995 and
      December 31, 1996, were identified. Costs were determined from several databases
      within the British Columbia (BC) Ministry of Health, as well as from BC Cancer
      Agency patient charts. The mean total cost to the health system was CDN
      $36,474.33 (95% confidence interval $29,752-$43,196) per subject. The mean costs
      were highest for the youngest age group and lowest for the middle age group, but
      these only differed by $2,300. Inpatient costs accounted for the greatest
      proportion of the total, over 50% in all age groups. This data may be valuable in
      assessing the cost-effectiveness of interventions that are known to affect
      mortality due to breast cancer.

PMID- 11336246
TI  - Relationship of estrogen and progesterone receptor protein levels in
      carcinomatous and adjacent non-neoplastic epithelium of the breast: a
      histopathologic and image cytometric study.
AB  - BACKGROUND: Results of a previous study demonstrating a correlation between
      steroid hormone receptor concentrations in benign and tumor tissue in patients
      with breast carcinoma suggest that receptor levels in breast epithelium
      undergoing malignant transformation may play a role in determining the receptor
      levels in the resulting carcinoma. Data used in that study were derived from
      ligand binding assays and may reflect shortcomings inherent in this methodology,
      particularly the dilution of receptor proteins from benign and malignant
      epithelial cells by stromal components. METHODS: We performed a correlation study
      of steroid hormone receptor expression in benign and malignant breast epithelial
      cells using computerized image cytometry and histologic sections stained for
      estrogen (ER) and progesterone receptor (PR), avoiding the problems of
      contribution of stromal cells to the measurements and uncertainty about the
      histologic composition of the sample. Sections which contained both tumor and non
      neoplastic breast elements were obtained from surgical specimens from 50 patients
      with breast carcinoma. RESULTS: Positive area (PA) scores for ER in benign and
      malignant epithelium showed direct correlation that was significant (r = 0.46, p
      < 0.001), whereas those for PR, although trended in the same direction, did not
      (r = 0.17, p > 0.2). PA levels for both receptor proteins were higher in benign
      breast epithelium with proliferative features, compared to non-proliferative
      benign epithelium, and in tumors when the associated benign tissue had
      proliferative changes, but neither of these differences were statistically
      significant, suggesting that the correlation of ER levels in benign and malignant
      epithelium was not simply a function of proliferative change. CONCLUSION: Our
      results provide support for the concept that ER expression in breast carcinoma
      depends partially on epithelial cell receptor levels in the breast in which it
      arises, but not for the analogous hypothesis for PR. When costs and benefits of
      tamoxifen chemoprevention are weighed for a patient at risk for breast carcinoma,
      and when cyto- or histopathologic breast tissue specimens are available, it may
      be reasonable to include breast epithelial ER levels among the factors considered
      in making the treatment decision.

PMID- 11336248
TI  - Percentage of blocks with DCIS.

PMID- 11336247
TI  - Three-dimensional helical CT of the breast: accuracy for measuring extent of
      breast cancer candidates for breast conserving surgery.
AB  - OBJECTIVE: To evaluate the accuracy of three-dimensional (3D) helical computed
      tomography (CT) for assessing the extent of breast cancer of candidates for
      breast conserving surgery. METHODS: Results of helical CT were studied in 144
      lesions of 144 patients with breast cancer before breast-conserving surgery. A
      lesion was defined as positive if focal enhancement was detected by CT within 100
      s after contrast material administration. After resection, tumors were
      histopathologically mapped and correlated with the extent of 3D images. RESULTS:
      Helical CT enabled detection of 143 tumors but not of one ductal carcinoma in
      situ (DCIS). The median deviation of the tumor extension revealed by 3D helical
      CT images from pathological assessment was 7.7 mm (range 0-60 mm). The extent of
      tumors was significantly correlated with CT measurements (r = 0.714, p < 0.0001).
      By multivariate analysis, the presence of invasive tumors with intraductal
      extensions beyond the edge of the invasive tumor and histologic type (DCIS) were
      significant risk factors for deviation of the tumor extension revealed by 3D
      helical CT images from pathological assessment. CONCLUSION: Three dimensional
      helical CT of the breast is an accurate preoperative imaging modality for
      assessing the extent of breast cancer candidates for breast conserving surgery.

PMID- 11336249
TI  - A serine endopeptidase from the fruits of Melothria japonica (Thunb.) maxim.
AB  - An endopeptidase from the fruits of Melothria japonica (Thunb.) Maxim. has been
      purified by DEAE-Sepharose chromatography and gel-filtration by a Sephacryl S
      300. The enzyme has Mr of 61 kDa. The optimum pH of the enzyme was 8. The enzyme
      activity was inhibited by diisopropyl fluorophosphate and
      phenylmethanesulfonylfluoride, but not by EDTA. Casein was a poor substrate, but
      angiotensin I was cleaved by the enzyme within 30 min at four different sites.
      These results indicated that the enzyme was a serine oligopeptidase of broad
      substrate specificity.

PMID- 11336250
TI  - A sesquiterpene drimane with antinociceptive activity from Drimys winteri bark.
AB  - Along with three known drimanes, polygodial. 1-beta-(p-methoxycinnamoyl)
      polygodial and mukaadial, the sesquiterpene drimane named drimanial was isolated
      from the bark of Drimys winteri (Winteraceae). Its structure was elucidated based
      on spectroscopic evidence. Drimanial exhibited antinociceptive action against
      acetic acid induced pain, being about 3-fold less active than polygodial.

PMID- 11336251
TI  - Allelopathic sesquiterpenoids from rhizomes of Petasites japonicus ssp. giganteus
      Kitam.
AB  - Four sesquiterpenoids were isolated from Petasites japonicus (Siebold and Zucc.)
      Maxim. ssp. giganteus (F. Schmidt ex Trautv.) Kitam. (Compositae, Japanese name:
      Akitabuki) as allelochemicals. Their structures were elucidated on the basis of
      spectroscopic methods and their allelopathic effects were assessed.

PMID- 11336252
TI  - Cuticular waxes on eceriferum mutants of Arabidopsis thaliana.
AB  - We present cuticular wax chemical profiles for the leaves and stems of
      Arabidopsis wildtype Landsberg erecta and eleven isogenic eceriferum mutants:
      cer5, cer10 to cer15, and cer17 to cer20. These cer mutants have wax profiles
      that are different from those of wildtype in chemical chain length distribution,
      amount per chemical class, and/or total wax load. Analyses of detailed leaf and
      stem wax profiles for these cer mutants have allowed us to place some of these
      mutants at specific steps in wax production. The cer13 gene is predicted to
      affect release of the 30 carbon fatty acid from the elongation complex or the
      reduction of C30 fatty acid to C30 aldehyde. The CER19 gene product is predicted
      to be involved in C28 to C30 fatty acyl-CoA elongation. The CER20 gene is
      predicted to affect the oxidation of C29 alkane to C29 secondary alcohol. Several
      predicted gene products affect only stem specific steps in the wax pathway.

PMID- 11336253
TI  - Melampolides from Enydra anagallis.
AB  - The investigation of an Argentine collection of Enydra anagallis afforded
      sesquiterpene lactones of the melampolide type two of which were previously
      known. Their structures were elucidated by spectroscopic methods.

PMID- 11336254
TI  - ent-Pimarane derivatives from Dysoxylum hainanense.
AB  - Four ent-pimarene diterpenoids. ent-18-acetoxy-8(14)-pimarene-15S, 16-diol, ent
      18-acetoxy-16-hydroxy-8(14)-pimaren-15-one, ent-16,18-dihydroxy-8(14)-pimaren-15
      one and ent-19-nor-4,16,18-trihydroxy-8(14)-pimaren-15-one, together with three
      known damarane triterpenoids, richenoic acid, eichleriainic acid and shoreic acid
      were isolated from the bark of Dysoxyhum hainanense Merr. Their structures were
      elucidated on the basis of spectroscopic techniques. The absolute configurations
      of four diterpenoids were assigned as ent-pimarene type by chemical
      transformation and by co-occurrence in the plant as well as by negative optical
      rotations for four compounds.

PMID- 11336255
TI  - Terpenoids and gamma-pyrone derivatives from Prangos tschimganica.
AB  - The methanol extract of the dried aerial parts of Prangos tschimganica afforded
      seven monoterpenoids and four gamma-pyrone derivatives. Their structures were
      established on the basis of chemical and spectroscopic evidence.

PMID- 11336256
TI  - Seasonal variation in the content of hydrolysable tannins in leaves of Betula
      pubescens.
AB  - The contents of 13 hydrolysable tannins in the leaves of white birch (Betula
      pubescens L.) trees were analysed at twelve stages throughout the growing season.
      All individual galloylglucoses, from 1-O-galloyl-beta-D-glucopyranose to
      1,2,3,4,6-penta-O-galloyl-beta-D-glucopyranose, accumulated in young leaves,
      while ellagitannins showed significantly variable seasonal trends. The major
      ellagitannin during the whole growing season was pedunculagin while 2,3-(S)-HHDP
      glucopyranose. the end product of the proposed ellagitannin pathway, accumulated
      in mature leaves. Relationships between the characteristics of seasonal variation
      in the contents of individual ellagitannins and their chemical structures were
      used to unravel the biogenesis of ellagitannins in birch leaves. Evidence of
      degradation of ellagitannins through hydrolysis during leaf growth and
      development is presented and implications for herbivory are discussed.

PMID- 11336257
TI  - The biosynthesis of benzoic acid glucosinolate esters in Arabidopsis thaliana.
AB  - The siliques and seeds of Arabidopsis thaliana accumulate a series of
      glucosinolates containing an alkyl side chain of varying length with a terminal
      benzoate ester function. The biosynthesis of these unusual nitrogen- and sulfur
      containing natural products was investigated by feeding isotopically-labeled
      precursors to detached flowering stems. Glucosinolates were extracted, purified
      and analyzed by tandem mass spectrometry. Phenylalanine and benzoic acid were
      incorporated into the benzoate ester function, and methionine and acetate were
      incorporated into the aliphatic portion of the side chain in a position-specific
      manner. The labeling patterns observed were consistent with the chain extension
      of methionine by a three-step elongation cycle which begins with the condensation
      of acetyl-CoA with a 2-oxo acid derived from methionine and ends with an
      oxidative decarboxylation forming a new 2-oxo acid with an additional methylene
      group. Incorporation of desulfo-4-methylthiobutyl glucosinolate into 4
      benzoyloxybutyl olucosinolate suggested chain-extended methionine derivatives are
      first converted to their corresponding methylthioalkyl glucosinolates with
      further side chain modification occurring later. Transformation of the
      methylthiol function to a hydroxyl group is followed by esterification with
      benzoic acid. The siliques appear to possess the complete machinery for carrying
      out all of the reactions in the biosyntheis of these complex glucosinolates.

PMID- 11336258
TI  - Tracer studies with 13C-labeled carbohydrates in cultured plant cells.
      Retrobiosynthetic analysis of chelidonic acid biosynthesis.
AB  - The biosynthesis of chelidonic acid was studied in cell suspension cultures of
      Leucojum aestivum. Cell cultures were supplied with [U-13C]glucose, [l
      13C]glucose or [U-13Cs]ribose/ribulose in standard medium containing unlabeled
      glucose. 13C labeling patterns of amino acids obtained by hydrolysis of biomass
      were determined by NMR spectroscopy and compared to the labeling pattern of
      chelidonic acid. The data document the incorporation of a contiguous 4-carbon
      fragment derived from the pentose phosphate pool into chelidonic acid. This
      suggests a biosynthetic pathway involving the condensation of phosphoenolpyruvate
      with a pentose phosphate followed by dehydration, dehydrogenation, ring closure
      and decarboxylation conducive to the loss of C-5 of the pentose precursor.

PMID- 11336259
TI  - Equilibrium between basic nitrogen compounds in lupin seeds with differentiated
      alkaloid content.
AB  - The results of studies on the content of the nitrogen basic compounds, viz.
      quinolizidine alkaloids, biogenic polyamines and basic amino acids in lupin seeds
      are presented. The investigations concerned three lupin species (Lupinus
      angustifolius L., Lupinus albus L. and Lupinus luteus L.) and 10 bitter and sweet
      cultivated varieties. Content of quinolizidine alkaloids in L. angustifolus
      ranged from 11.4 to 19.6 microg mg(-1) dw (bitter cultivars), from 0.18 to 0.47
      microg mg(-1) dw (sweet), in L. albus from 0.58 microg mg(-1) dw (sweet) to 29.6
      microg mg(-1) dw (bitter) and in L. luteus from 0.59 (sweet) to 14.7 microg mg(
      1) dw (bitter). Total biogenic polyamine content ranged in L. angustifolius from
      2,773.9 to 3,180.2 pmol mg(-1) dw (bitter) and from 315.0 to 599.0 pmol mg(-1) dw
      (sweet), in L. albus from 432.6 pmol mg(-1) dw (sweet) to 1,832.0 pmol mg(-1) dw
      (bitter) and in L. luteus from 506.9 pmol mg(-1) dw (sweet) to 2,091.8 pmol mg(
      1) dw (bitter). Total basic amino acids varied in L. angustifolus from 1,034.3 to
      1,704.6 pmol mg(-1) dw (bitter) and from 1,761.9 to 2,101.9 pmol mg(-1) dw
      (sweet), in L. albus from 696.9 pmol mg(-1) dw (bitter) to 1,269.2 pmol mg(-1) dw
      (sweet) and in L. luteus from 927.6 pmol mg(-1) dw (bitter) to 1,598.3 pmol mg(
      1) dw (sweet). We found a close dependence between alkaloid content and level of
      biogenic polyamines and basic amino acids in all three lupin species tested. All
      bitter lupin seeds also contain high level of biogenic polyamines but a low
      content of basic amino acids. The reverse relationship in sweet lupin seeds was
      found. The findings demonstrate that lupin nitrogen basic compounds are in steady
      equilibrium and that change of content in one compound leads to corresponding
      change in the content of another.

PMID- 11336260
TI  - Transformation of naturally-occurring 1,9-trans-9,5-cis sweroside to all trans
      sweroside during acetylation of sweroside aglycone.
AB  - From the rootstock of Scabiosa columbria L. loganin and sweroside were isolated.
      Sweroside showed moderate antibacterial activity. Pure sweroside was converted to
      the sweroside aglycone 1-acetoxy derivative (DABCO/Ac2O) after hydrolysis of the
      glucose unit. X-ray crystallography of the monoacetate showed unambiguously that
      it had been transformed to a new seco-iridoid having the novel trans diaxial
      configuration for the protons on C-1, C-9 and C-5. The mechanism for the
      rearrangement is discussed.

PMID- 11336261
TI  - Insecticidal flavaglines and other compounds from Fijian Aglaia species.
AB  - Bioassays with lipophilic crude extracts of four Fijian Aglaia species against
      Spodoptera littoralis displayed strong insecticidal activity for A. basiphylla
      and A. gracilis, whereas A. archboldiana and A. vitiensis did not have any
      significant effects. The insect toxicity of A. basiphylla was caused by the well
      known benzofuran flavaglines rocaglamide, desmethylrocaglamide and aglafoline. In
      contrast, A. gracilis contained four related pyrimidinone derivatives in the root
      and stem bark, including two new congeners named marikarin and 3'
      hydroxymarikarin. Moreover, two new putrescine bisamides, secoodorine and
      secopiriferine, a new benzopyran flavagline. desacetylaglain A. and a new
      norsesquiterpene were isolated from the leaves together with three known
      bisamides and 3-hydroxy-5,7,4'-trimethoxyflavone. The structures of the new
      compounds were elucidated by spectroscopic methods. Comparative feeding assays
      within the active pyrimidinone flavaglines showed that the free hydroxy group in
      aromatic ring A of marikarin diminishes insecticidal activity.

PMID- 11336262
TI  - The essential oil of Origanum vulgare L. ssp. vulgare growing wild in vilnius
      district (Lithuania).
AB  - The plants of wild Origanum vulgare L. ssp. vulgare were collected in 10
      localities of Vilnius district (Lithuania) in 1995-1999. The main constituents of
      the essential oils from 8 localities were beta-ocimene (14.9-21.6%), germacrene D
      (10.0-16.2), beta-caryophyllene (10.8- 15.7%) and sabinene (6.6- 4.2%). The
      essential oils from two localities contained only three above compounds as major
      components: germacrene D, beta-ocimene and sabinene or beta-caryophyllene, beta
      ocimene and germacrene D. Three chemotypes of essential oils were identified. The
      main chemotype was beta-ocimene germacrene D-beta-caryophyllene. The terpenic
      hydrocarbons made up 52.8-80.6% of the essential oils. The 42 identified
      components made up 85.6-98.0% of the essential oil.

PMID- 11336263
TI  - Biosynthesis of the hemi- and monoterpene moieties of isoprenyl phenyl ethers
      from the liverwort Trichocolea tomentella.
AB  - The incorporation of 13C labelled glucose into trichocolein, deoxytomentellin,
      trans-phytol and stigmasterol has been studied in axenic cultures of the
      liverwort Trichocolea tomentella. Quantitative 13C NMR spectroscopic analysis of
      the resulting labelling patterns showed that the isoprene units of the hemi- and
      monoterpenoid moieties and the diterpene phytol are derived from the
      methylerythritol phosphate pathway, whereas the isoprene units of stigmasterol
      are built up via the mevalonic acid pathway. These results indicate the
      involvement of both IPP biosynthetic pathways in different cellular compartments.
      A new, hydroperoxy geranyl phenyl ether derivative is also described.

PMID- 11336264
TI  - Variability of essential oils of Satureja montana L. and Satureja kitaibelii
      wierzb. ex Heuff. from the central part of the balkan peninsula.
AB  - The results of the essential oil composition confirm that there are differences
      between populations within the same subspecies (Satureja montana ssp. montana,
      between the subspecies (Satureja montana ssp. montana and Satureja montana ssp.
      pisidica) and the species (Satureja montana and S. kitabelii). The essential oil
      composition of S. montana ssp. montana is more related to the Satureja montana
      ssp. pisidica than S. kitaibelii which separates as a whole species.

PMID- 11336265
TI  - Prenylated flavonoids from Deguelia hatschbachii and their systematic
      significance in Deguelia.
AB  - Chemical investigation of dichloromethane and petrol extracts from the roots of
      D. hatshbachii A. M. G. Azevedo furnished thirteen compounds from which five are
      described for the first time and their structures were determined to be 3-(4'
      hydroxyphenyl)-5-methoxy-6-( 3,3-dimethylallyl)-2"2"-dimethylchromene-(5",6":8,7)
      3-(propyl-2-one)-4H-1-benzo-2,3-dihydropyran-2,4-dione; 6,4'-dihydroxy-3-(3,3
      dimethylallyl)-2",2"-dimethylchromene (5",6":5,4)-2-methoxy deoxybenzoin; 6.4'
      dihydroxy-3-(3,3-dimethylallyl)-2",2"-dimethylchromene (5",6":5,4)-2-methoxy-8
      (propyl-2-one) deoxybenzon; 6-(3,3-dimethylallyl)-2",2"-dimethylchromene
      (5",6":4.5)-4'-hydroxy-3-methoxy stilbene and 3,5-dimethoxy-4'-hydroxy-4-(3,3
      dimethylallyl) stilbene by spectral analysis (UV, IR, MS and ID- and 2D- NMR
      experiments). The root extracts and some isolated compounds were bioactive, as
      revealed by bioautography and brine shrimp lethality assays.

PMID- 11336266
TI  - Effect of (+)-pulegone and other oil components of Mentha x Piperita on cucumber
      respiration.
AB  - Peppermint (Mentha x piperita L.) essential oil and main components were assessed
      for their ability to interfere with plant respiratory functions. Tests were
      conducted on both root segments and mitochondria isolated by etiolated seedlings
      of cucumber (Cucumis sativus L.). Total essential oil inhibited 50% of root and
      mitochondrial respiration (IC50) when used at 324 and 593 ppm, respectively. (+)
      Pulegone was the most toxic compound, with a 0.08 and 0.12 mM IC50 for root and
      mitochondrial respiration, respectively. (-)-Menthone. followed (+)-pulegone in
      its inhibitory action (IC50 values of 1.11 and 2.30 mM for root and mitochondrial
      respiration respectively), whereas (-)-menthol was the less inhibitory compound
      (IC50 values of 1.85 and 3.80 mM respectively). A positive correlation was found
      for (+)-pulegone, (-)-menthone and (-)-menthol between water solubility and
      respiratory inhibition. The uncoupling agent. carbonyl-cyanide-m-chlorophenyl
      hydrazone (CCCP), lowered (-)-menthol and (-)menthone inhibition and annulled (+)
      pulegone inhibition of mitochondrial respiration, whereas salicyl-hydroxamic acid
      (SHAM) 2-hydroxybenzohydroxamic acid, the alternative oxidase (AO) inhibitor,
      increased (-)-menthone inhibition and annulled both (+)-pulegone and (-)-menthol
      inhibitory activity. The possible interaction of (-)-pulegone and (-)-menthol
      with AO and the mechanism of action of(+)-pulegone, (-)-menthone and (-)-menthol
      on mitochondrial respiration are discussed.

PMID- 11336267
TI  - Antifungal activity of the essential oil of flowerheads of garland chrysanthemum
      (Chrysanthemum coronarium) against agricultural pathogens.
AB  - The antifungal activity of Chrysamthemum coronarium was evaluated against 12
      agricultural pathogens. Flowerhead oil was active both in contact and headspace
      in vitro assays producing hyphal growth inhibition, although there was less
      activity on faster growing fungi. The main compounds identified in the oil were
      camphor (29.2%), alpha-pinene (14.8%), beta-pinene (9.5%) and lyratyl acetate
      (9.8%). The blue color of the oil was due to the presence of chamazulene (0.5%).

PMID- 11336268
TI  - Prevalence and annual risk of tuberculosis infection in Laos.
AB  - SETTING: Laos, where the implementation of a national tuberculosis program
      started in 1995. OBJECTIVE: To estimate the prevalence (P) and annual risk of
      tuberculosis infection (ARTI) and relate this to case rates in the tuberculosis
      program. METHODS: Tuberculin survey in schools in Vientiane municipality and
      three provinces. Sampling was not representative, but included schools in
      accessible districts in provinces with different characteristics. A group of 150
      tuberculosis patients were tested for comparison. RESULTS: An intra-dermal
      tuberculin test (PPD RT23/ Tween80) was applied to 11237 children; 9968 reactions
      were read, 4035 among first and second grade children with no BCG scar: 818 in
      Vientiane (mean age 8.4), 803 in Savannakhet (8.9), 1563 in Xiengkhuang (8.4),
      and 851 in Luangprabang (7.9). If reactions of > or =10 mm are counted, ARTI is
      estimated as 1.1% for the areas included in the survey with a strong variation by
      province (Vientiane 1.3%; Savannakhet 1.4%; Luangprabang 0.6%; Xiengkhuang 0.1%).
      The difference in ARTI is in accordance with differences in reported case rates
      in the provinces. The ARTI varied from 0.5% to 1.2%, depending on the method used
      for calculating P (Vientiane 0.6%-1.4%; Savannakhet 0.5-1.5%; Xiengkhuang 0.1%
      0.2%; Luangprabang 0.4%-0.9%). CONCLUSIONS: The ARTI is unequally distributed
      geographically and/or by ethnic group. It is generally higher in south and lower
      in central and north Laos. Improved methods are needed for estimating the
      prevalence of infection.

PMID- 11336269
TI  - Tuberculosis prevalence in an urban jail: 1994 and 1998.
AB  - SETTING: Despite a continuing decline in tuberculosis (TB) in the US, jails
      remain a high-risk setting for the identification of active and latent TB
      infection (LTBI). OBJECTIVE: The purpose of this study was to document the change
      in TB prevalence in the San Francisco City and County Jail. DESIGN: Two period
      prevalence analyses were done, for 1994 and 1998. The sample included all persons
      booked into jail during the two years. The rates of inmates screened and the
      prevalence of active TB and LTBI by sex and ethnicity were compared using
      computerized records. RESULTS: Prevalence of active TB was 72.1 per 100000 jail
      population for 1998, and did not change significantly from 1994. In 1998 one
      third of active TB cases were found through jail screening. Latinos represented
      respectively 20.1% and 17.7% of those booked in 1994 and 1998, but 43.0% and
      41.7% of inmates with LTBI. In 1998, being Latino (odds ratio 2.9) and male (odds
      ratio 1.6) were most strongly associated with LTBI. CONCLUSION: Screening for TB
      among jail inmates is an increasingly valuable clinical and epidemiological tool
      for case-finding and for identifying persons who would benefit from preventive
      therapy.

PMID- 11336271
TI  - Risk factors for nosocomial transmission of multidrug-resistant tuberculosis due
      to Mycobacterium bovis among HIV-infected patients.
AB  - OBJECTIVE: To identify risk factors for transmission of multidrug-resistant
      tuberculosis (MDR-TB) among hospitalized human immunodeficiency virus (HIV)
      infected patients exposed during a nosocomial outbreak. DESIGN: Case control
      study. Cases were HIV-infected patients with MDR-TB due to Mycobacterium bovis
      (MDR-TBMb) who acquired the disease after exposure to an MDR-TBMb patient in an
      hospital ward. Controls were HIV-infected patients exposed to a case of MDR-TBMb
      in an hospital ward but who did not develop MDR-TBMb during the follow-up.
      RESULTS: Nineteen cases and 31 controls were included. CD4 cell counts were
      significantly lower among cases. Exposure in the infectious diseases ward or
      exposure to the index patient were associated with development of MDR-TBMb, while
      exposure during a single-room hospital stay and exposure in the respiratory
      isolation ward were associated with non-development of MDR-TBMb. A multiple
      regression logistic model showed that only a CD4 cell count below 50/microL and
      exposure to the index patient increased the risk of developing MDR-TBMb (P <
      0.05). Hospitalization in a single room seemed to protect HIV-infected patients
      from developing nosocomial MDR-TBMb (P = 0.052). CONCLUSIONS: Over classic risk
      factors, such as length of exposure or sharing a room with a case, severe
      immunosuppression independently increases the risk of MDR-TB transmission in the
      context of a nosocomial MDR-TB outbreak among HIV-infected patients. This
      information must be considered in the management of tuberculosis outbreaks.
      Patients with CD4 cell counts below 50/microL should be the principal group
      targeted for prevention strategies in nosocomial outbreaks.

PMID- 11336270
TI  - Trend in HIV prevalence among tuberculosis patients in Tanzania, 1991-1998.
AB  - OBJECTIVE: To determine the trend in human immunodeficiency virus (HIV)
      prevalence among tuberculosis patients in Tanzania and estimate what proportion
      of the increase in notification rates between the surveys was directly
      attributable to HIV infection. METHODS: Consecutive tuberculosis patients were
      enrolled over 6-month periods in most regions. Demographic and clinical data were
      collected on standard forms and a single HIV ELISA test performed. Trends in
      tuberculosis incidence were estimated from regional notification data. RESULTS:
      Of 10612 eligible tuberculosis patients, 44% had HIV infection, compared with 32%
      in the previous survey. The largest increase was observed in the youngest birth
      cohorts, suggesting active HIV transmission. Approximately 60% of the increase in
      notification rates of smear-positive tuberculosis between surveys was directly
      attributable to HIV infection. CONCLUSION: The HIV epidemic has had a strong
      influence on tuberculosis incidence. However, since 1995, tuberculosis
      notification data have increased less steeply, AIDS notifications have gone down,
      and HIV prevalence in blood donors has not increased a great deal. Another survey
      among tuberculosis patients in 5 years' time may show whether the HIV epidemic in
      Tanzania has reached a maximum or steady state.

PMID- 11336272
TI  - Screening for pulmonary tuberculosis among immigrants: estimated effect on
      severity of disease and duration of infectiousness.
AB  - OBJECTIVE: To estimate the effect of tuberculosis screening among recent
      immigrants on the severity of disease at diagnosis and on the duration of the
      infectious period. DESIGN: Comparison of pulmonary tuberculosis cases among
      immigrants detected through screening with those detected passively, using
      information from the Netherlands Tuberculosis Register. PARTICIPANTS: Immigrants
      from highly endemic countries diagnosed with culture-positive pulmonary
      tuberculosis within 30 months after arrival in The Netherlands, 1993 through
      1998. OUTCOME MEASURES: Severity of disease (smear-positive disease,
      hospitalisation, case fatality) and duration of symptomatic period. RESULTS: A
      total of 882 bacteriologically confirmed tuberculosis patients from highly
      endemic countries had been in The Netherlands less than 30 months, and were
      detected through screening (454), or passively (368). Compared with patients
      detected passively, patients found through screening were less often sputum smear
      positive (OR 0.5, 95%CI 0.3-0.8) and less often hospitalised (OR 0.2, 95%CI 0.1
      0.2). Those detected through screening had a shorter symptomatic period.
      Screening is estimated to have reduced the infectious period by approximately
      33%. CONCLUSION: The screening programme detected cases earlier, resulting in
      fewer hospital admissions, shorter duration of symptoms and therefore probably
      reduced tuberculosis transmission.

PMID- 11336273
TI  - Family outbreaks of tuberculosis in South Moravia, a low incidence area of the
      Czech Republic.
AB  - OBJECTIVES: To identify suspected family outbreaks of tuberculosis in South
      Moravia, an area with the lowest notification rates in the Czech Republic.
      METHOD: The insertion sequence IS6110-based RFLP analysis of Mycobacterium
      tuberculosis was applied in isolates collected from 17 indigenous excretors
      giving the same family name and/or domicile. The fingerprints were matched with a
      database of 184 RFLP profiles of Czech M. tuberculosis isolates originating from
      remote localities. RESULTS: The RFLP analysis revealed uniform fingerprints in
      each of six indigenous outbreaks consisting of two to six family members or
      relatives. In three of them no matching case has been found in the Czech
      fingerprint database. The remaining three clusters showed identical patterns with
      RFLP profiles of 13 Czech M. tuberculosis strains originating from remote areas:
      five were from patients living in the immediate vicinity and eight were from
      distant regions. CONCLUSION: Different clustered genotypes of M. tuberculosis
      were identified in epidemiologically linked family outbreaks of tuberculosis,
      half of them indigenous and half matching fingerprints of strains from remote
      areas. It seems that family outbreaks may contribute to the continued occurrence
      of tuberculosis in South Moravia, which reports the lowest notification values in
      the Czech Republic.

PMID- 11336274
TI  - Proposing indicators for evaluation of tuberculosis control programmes in large
      cities based on the experience of Barcelona.
AB  - OBJECTIVE: To evaluate the effectiveness of the Barcelona Tuberculosis (TB)
      Control Programme and to propose evaluation indicators. MATERIALS AND METHODS:
      Using quantitative indicators, the results and impact of the programme over the
      period 1987 to 1999 were evaluated. Statistical analysis was based on a
      description of indicators, including tests for trends, and on the evolution of
      the incidence. RESULTS: The incidence of tuberculosis rose between 1987 and 1991
      (P = 0.10), and fell between 1991 and 1999 (P < 0.001). During the study period
      statistically significant improvements were observed in the percentage of cases
      notified by the medical profession, adherence to treatment and the percentage of
      cases on directly observed treatment (DOT), and meningitis among children aged 0
      to 4 years fell notably. However, diagnostic delay in smear-positive cases and
      the percentage of cases whose contacts were examined did not vary significantly.
      The evaluation indicated an average annual decline in tuberculosis incidence of
      6.7%, and rates of adherence to treatment (94.5% among smear-positive cases)
      achieved their objectives. The average median diagnostic delay (36 days) and the
      percentage of cases with contacts examined (mean 59.8%) were rather less
      optimistic. CONCLUSIONS: The results of the evaluation were in general positive.
      Decline in incidence, meningitis in children, treatment adherence rates,
      diagnostic delay and percentage of cases with studied contacts were considered
      the best indicators for evaluation of TB programmes.

PMID- 11336275
TI  - Cooking with biomass stoves and tuberculosis: a case control study.
AB  - OBJECTIVE: To search for an association between tuberculosis and use of biomass
      stoves found recently in a cross sectional study. DESIGN: In a case-control study
      based in a chest referral hospital, the cases were 288 patients with active smear
      positive or culture-positive tuberculosis, and the controls were 545 patients
      with ear nose and throat ailments with no evidence of chest disease studied at
      the same time as the cases. Exposure to present or previous biomass smoke by
      history of cooking with traditional wood stoves was assessed by positive or
      negative response. RESULTS: Exposure to biomass smoke was significantly higher in
      cases than in controls. Crude odds ratios for tuberculosis and biomass smoke
      exposure were 5.2 (95%CI 3.1-8.9) for current exposure, 3.4 (95%CI 2.4-5.0) for
      past or present exposure and 1.8 (95%CI 1.1-3.0) for past exposure. The
      association was observed only for patients living in Metropolitan Mexico City and
      urban or suburban areas in the center of Mexico providing most cases and
      controls. For rural areas, the power of the study was low and the origin of the
      patients heterogeneous. Odds ratio for Mexico City Metropolitan area and the
      center of Mexico was 2.4 (95%CI 1.04-5.6), adjusted for age, sex, level of
      education, crowding, smoking, socio-economic level, zone of residence and state
      of birth. In the same model smoking had an OR of 1.5 (95%CI 1.0-2.3) for
      tuberculosis. CONCLUSION: Our results support a causal role of current domestic
      biomass smoke exposure in tuberculosis.

PMID- 11336276
TI  - Substandard tuberculosis drugs on the global market and their simple detection.
AB  - SETTING: The prevalence of substandard anti-tuberculosis drugs is unknown. To
      maximize the effectiveness of tuberculosis (TB) control efforts, simple,
      inexpensive drug quality screening methods are needed. DESIGN: Isoniazid (INH)
      and rifampin (RMP) single- and fixed-dose combination (FDC) formulations were
      collected from selected TB programs and pharmacies in Colombia, Estonia, India,
      Latvia, Russia and Vietnam. Samples were screened using a recently developed thin
      layer chromatography (TLC) kit. All abnormal samples and a 40% random sample of
      normal formulations were further analyzed using confirmatory techniques. Samples
      outside of 85% to 115% of stated content, and/or containing compounds other than
      the stated drug, were defined as being substandard. RESULTS: Overall, 10% (4/40)
      of all samples, including 13% (4/30) RMP samples, contained <85% of stated
      content. More FDCs (5/24, 21%) than single-drug samples (2/16, 13%) were
      substandard. A comparison of TLC with the confirmatory analysis for RMP analysis
      showed a sensitivity of 100% (4/4), a specificity of 92% (24/26), a positive
      predictive value (PPV) of 67% (4/6), and a negative predictive value (NPV) of
      100% (24/24). An analysis of INH showed a specificity of 90% (9/10). However,
      sensitivity, PPV, and NVP could not be determined. CONCLUSION: A substantial
      number of anti-tuberculosis drugs from several countries, in particular FDCs,
      were found to be substandard. Such drugs may contribute to the creation of drug
      resistant TB. TLC is an effective, convenient, and inexpensive method for the
      detection of substandard drugs.

PMID- 11336277
TI  - Atypical radiological images of pulmonary tuberculosis in 192 diabetic patients:
      a comparative study.
AB  - SETTING: Comparative studies of pulmonary tuberculosis images in diabetics have
      yielded conflicting results. OBJECTIVE: To assess radiological images of
      pulmonary tuberculosis in a large population of diabetic patients. DESIGN:
      Radiographs from in-patients admitted with pulmonary tuberculosis and diabetes
      (TBDM group, n = 192) were reviewed and compared with a control group of patients
      with pulmonary tuberculosis alone (TB group, n = 130). RESULTS: Both groups had a
      similar evolution time of tuberculosis (approximately 2 years). Statistical
      differences were observed as follows: TBDM patients were older (51.3+/-0.9 vs. TB
      group 44.9+/-1.8 years, mean +/- SEM), and had a decreased frequency of upper
      (17% vs. 56%), and an increased frequency of lower (19% vs. 7%) and upper + lower
      (64% vs. 36%) lung field lesions. More TBDM patients developed cavitations (82%
      vs. 59%) more often in the lower lung fields (29% vs. 3%). More multiple cavities
      were seen in TBDM patients (25% vs. 2%). TBDM group had a lower total leukocyte
      count (8836.7+/-219.5 vs. 10013.1+/-345.2 cells/mm3), mainly due to a lower
      number of non-lymphocyte cells (6815.8+/-221.8 vs. 8095.7+/-321.9 cells/mm3).
      Multiple logistic regression showed that being a diabetic patient was the most
      important factor determining lower lung field lesions and cavities. CONCLUSIONS:
      This study in a large number of diabetics with pulmonary tuberculosis confirmed
      that their chest X-ray images significantly depart from the typical presentation.
      Clinicians must keep this in mind to avoid misdiagnosis.

PMID- 11336278
TI  - Performance of whole blood IFN-gamma test for tuberculosis diagnosis based on PPD
      or the specific antigens ESAT-6 and CFP-10.
AB  - OBJECTIVE: To evaluate the QuantiFERON-TB test in BCG-vaccinated, non-BCG
      vaccinated and tuberculosis (TB) patient donor groups, and to compare its
      diagnostic performance with that of a blood test based on the Mycobacterium
      tuberculosis specific antigens ESAT-6 and CFP-10. DESIGN: Analysis of the IFN
      gamma responses of whole blood cells from BCG-vaccinated or non-BCG-vaccinated
      donors or patients with tuberculosis, stimulated with PPD, ESAT-6 or CFP-10
      antigens, and evaluation of the specificity and sensitivity of the test. RESULTS:
      None of the non-vaccinated donors showed positive responses to M. tuberculosis
      PPD, ESAT-6 or CFP-10. In BCG-vaccinated donors, 9/19 (47%) donors responded to
      the QuantiFERON-TB test based on M. tuberculosis-PPD, whereas 2/19 (10.5%)
      responded to either ESAT-6 or CFP-10. Comparable levels of sensitivity were
      obtained with the QuantiFERON-TB test based on M. tuberculosis-PPD (79%) and ESAT
      6 or CFP-10 antigens (72%). CONCLUSION: Our results demonstrate that the whole
      blood test based on M. tuberculosis-PPD did not efficiently distinguish BCG
      vaccinated donors from individuals with disease due to M. tuberculosis. The
      introduction of new recombinant antigens specific for M. tuberculosis, such as
      ESAT-6 or CFP-10, should increase the specificity of the whole blood test and
      enable discrimination between TB infection, atypical mycobacterial reactivity and
      reactivity due to BCG vaccination. Such a test would provide a quantum
      improvement over the current practice of using the tuberculin skin test for TB
      control and elimination.

PMID- 11336279
TI  - Asthma symptoms in relation to building dampness and odour in older multifamily
      houses in Stockholm.
AB  - SETTING: Respiratory symptoms and hay fever in adults in relation to the indoor
      environment. OBJECTIVES: To study relationships between reports on respiratory
      symptoms and hay fever and building dampness and odours in older multifamily
      dwellings. DESIGN: A questionnaire study in a random sample of 231 multifamily
      buildings built before 1961, which included 4224 apartments. The response rate
      was 77% (n = 3241). Information on building characteristics was gathered from
      building owners and the central building register in Stockholm. Multiple logistic
      regression analysis was applied, adjusting for age, sex, current smoking,
      population density, type of ventilation and ownership. RESULTS: In total, 22%
      reported at least one sign of dampness, and 32% reported odour in the dwelling.
      All types of odours were more common in damp buildings. Reports on dampness and
      odours were related to asthma symptoms and current cough, even when adjusting for
      potential confounders. A combination of odour and signs of high air humidity was
      related to an increase in asthma symptoms (OR = 2.82; 95%CI 2.70-2.95) and
      current cough (OR = 5.29; 95%CI 4.99-5.62). Similar findings were observed for a
      combination of odour and history of water leakage in the last 5 years, with an
      increase in asthma symptoms (OR = 3.59; 95%CI 3.37-3.82) and current cough (OR =
      2.86; 95%CI 2.61-3.14). There was a dose-response relationship between
      respiratory symptoms and the number of signs of dampness. An association was also
      observed between dampness and a history of pollen allergy. CONCLUSIONS: Signs of
      high indoor air humidity, water leakage and odours were common, and related to
      respiratory symptoms. Exposure to odorous compounds from building dampness may be
      significant with respect to respiratory symptoms and possibly atopic
      sensitisation.

PMID- 11336280
TI  - Chest radiography in the diagnosis of pneumoconiosis.
AB  - SETTING: Report of a workshop on Occupational Lung Diseases, IUATLD Respiratory
      Disease Section, Bangkok 1998. OBJECTIVE: To describe the role of chest
      radiography in the diagnosis of pneumoconiosis in clinical practice. MATERIALS
      AND METHODS: Pneumoconiosis, defined as the accumulation of dust in the lung and
      tissue reaction to its presence, is diagnosed and monitored by X-ray techniques.
      The International Labour Organization (ILO) developed a descriptive system of the
      radiographic appearances of pneumoconiosis using standard chest radiographs to
      classify the type and category of profusion of small opacities seen in the lung
      fields, as well as the width and extent of pleural changes and other
      abnormalities of a more general nature. RESULTS: The pertinence of the ILO
      classification has been demonstrated by studying the correlation between anatomic
      lesions and chest X-ray features. Other imaging techniques have been proposed
      over the past few years, including computed tomography and magnetic resonance
      imaging. However, until now they have remained essentially complementary to
      verify an unclear aspect of particular features of a given radiograph, rather
      than as the standard method of diagnosis. CONCLUSION: Chest radiography remains
      the principal tool in the diagnosis of pneumoconiosis, and has the advantages of
      the large number of units in service throughout the world, their relatively low
      cost, and the widely-accepted ILO classification.

PMID- 11336281
TI  - Is oral intermittent initial phase anti-tuberculosis treatment associated with
      higher mortality in high HIV-prevalent areas in sub-Saharan Africa?
AB  - The Malawi Tuberculosis Programme has evaluated an oral ambulatory treatment
      regimen (2R3H3Z3E3/6HE) in five districts, and observed a mortality rate of 23%
      in 2671 new patients with smear-positive pulmonary tuberculosis (PTB). Three
      studies were performed comparing treatment outcomes between patients treated with
      2R3H3Z3E3/6HE and 2SRHZ/6HE using historical data in the same districts and
      concurrent data in different districts. Using historical comparisons, mortality
      was significantly higher with 2R3H3Z3E3/6HE than 2SRHZ/6HE. Using concurrent
      comparisons, mortality was similar, although there was a higher death rate in the
      first month with the intermittent regimen. The intermittent regimen may be
      inferior to the established regimen.

PMID- 11336282
TI  - Why tuberculosis control in an unstable country is essential: desperate TB
      patients embrace DOTS in Angola.
AB  - After decades of war, the tuberculosis situation in Angola is alarming. The
      author describes his experiences with the implementation of a DOTS TB programme
      adapted to the difficult circumstances in a town partly inhabited by displaced
      people. The high motivation of both patients and health care workers is an
      important factor for its successful implementation. The need for international
      support of tuberculosis control programmes also in war-ridden countries is
      stressed.

PMID- 11336283
TI  - HIV-associated tuberculosis in the era of highly active antiretroviral therapy.

PMID- 11336284
TI  - Local anti-tuberculosis association (TB mahibers) and tuberculosis control in a
      rural district in Ethiopia.

PMID- 11336285
TI  - Triterpenoids.

PMID- 11336286
TI  - Beta-phenylethylamines and the isoquinoline alkaloids.

PMID- 11336287
TI  - Biotransformation of organic sulfides.

PMID- 11336288
TI  - Biochemistry of natural rubber, a vital raw material, emphasizing biosynthetic
      rate, molecular weight and compartmentalization, in evolutionarily divergent
      plant species.

PMID- 11336289
TI  - Type I polyketide biosynthesis in bacteria (Part A--erythromycin biosynthesis).

PMID- 11336290
TI  - Hot off the press.

PMID- 11336291
TI  - In vitro biocompatibility of biodegradable dextran-based hydrogels tested with
      human fibroblasts.
AB  - The cytotoxicity of dextran T40, methacrylated dextran (dex-MA) and hydroxyethyl
      methacrylated dextran (dex-HEMA), dextran-based hydrogel discs and microspheres,
      and their degradation products, was studied by measuring the cell proliferation
      inhibition index (CPII) on human fibroblasts in vitro. In addition, during the 72
      h incubation period light-microscopic observations were performed daily. After 24
      h of incubation with dextran and dex-HEMA polymers, the cells showed elongated or
      spider-like forms, some lipid droplets and intracellular granula, indicative of
      pinocytosis and internalization of the polymers. During the next two days, the
      fibroblasts' appearance did not change. Methacrylic acid (MAA), formed by
      hydrolysis of dex-HEMA, did not influence the cell morphology. Dex-HEMA polymer
      solutions with a low and high degree of substitution (DS) at 100 mg/ml caused a
      CPII of 30-40% after 72 h. This is less than 10% growth inhibition per cell cycle
      and statistically not different from the CPII induced by 100 mg/ml dextran T40.
      Growth inhibition induced by MAA was also low. The various dex-MA hydrogel discs
      caused similar low growth inhibition. Interestingly, hydrogel microspheres of dex
      MA and dex-(lactate-)HEMA caused a CPII of only 0-20% after 72 h. The results
      presented in this study demonstrate that methacrylate-derivatized dextran
      hydrogels show good biocompatibility in vitro making these degradable
      biomaterials promising systems for drug delivery purposes.

PMID- 11336292
TI  - Preparation of porous composite implant materials by in situ polymerization of
      porous apatite containing epsilon-caprolactone or methyl methacrylate.
AB  - Biodegradable and biostable composite foams were formed from porous apatite
      cement infiltrated with epsilon-caprolactone (CL) or methylmethacrylate (MMA)
      using a high over vacuum. For CL composites in situ polymerization was induced
      using trace water as an initiator and heating at 120 degrees C for up to 10 days
      or at 80 degrees C for 60 days. MMA composites were polymerized using AIBN
      initiator at 70 degrees C for 8 h. CL preparations gave composites with a
      polycaprolactone (PCL) number average of molecular weight (Mn) up to the maximum
      of 7.1 x 10(3) g/mol after 10 days and 16.8 x 10(3) g/mol after 60 days. The PCL
      and PMMA contents were close to 50 and 40 wt%, respectively, polymer was present
      as a thin coating on the apatite crystal plates and was evenly distributed
      throughout the samples. Re-evacuation of apatite saturated with monomer during
      preparation ensured that the upwards of 200 nm microchannels within the apatite
      cement were largely free of polymer, and the overall macroporous structure of the
      apatite foams was partly retained. Maximum compressive strengths increased from 9
      MPa to 37 and 64 MPa for PCL and PMMA composites, respectively. The water drop
      contact angle of the PCL composite was 64 degrees, and therefore suitable for
      cell attachment. PMMA composite surfaces were more hydrophobic. Composites were
      subjected to corona discharge to induce suitable moderate hydrophilicity at the
      surface.

PMID- 11336293
TI  - Intact microglia are cultured and non-invasively harvested without pathological
      activation using a novel cultured cell recovery method.
AB  - Because spontaneous host regeneration of damaged tissues is limited, novel
      therapeutics utilizing cultured cells with the aid of tissue engineering methods
      are promising alternatives for tissue replacement. One critical shortcoming is
      current requirement for invasive cell harvest from culture to fabricate cell
      based devices. Although microglia that secrete neurotrophic factors are
      attractive candidates for novel cell transplantation therapy for damaged central
      nervous system tissue, the intact harvest of cultured microglia is presently not
      achievable. Therefore, primary microglia were plated onto culture surfaces
      grafted with the temperature-responsive polymer, poly(N-isopropylacrylamide)
      (PIPAAm). This surface undergoes rapid, reversible temperature-dependent changes
      in its hydration state and surface hydrophilicity. Microglia attached and
      proliferated on PIPAAm-grafted dishes at 37 degrees C. By reducing culture
      temperature, more than 90% of the cells spontaneously detached from the dishes
      within several minutes without trypsin or EDTA treatment. Recovered and replated
      microglia exhibited phenotypic properties comparable to those of primary
      microglia freshly isolated from brain. By contrast, less than 60% of the cells
      were harvested by trypsin digestion, and exhibited significant alteration of
      characteristic cellular properties as monitored by pathological states in vivo.
      This new technology exhibits utility for the preparation of cell sources required
      for cell transplantation as well as microglial function analysis.

PMID- 11336294
TI  - Processing of HA-coated Ti-6Al-4V by a ceramic slurry approach: an in vitro
      study.
AB  - Hydroxyapatite-coated titanium alloy composite powders (Ti-6Al-4V/HA) was
      produced by a ceramic slurry approach. The aim was to evaluate the stability of
      the coating when subjected to a physiological medium simulated body fluid (SBF).
      Three consolidation conditions (700 degrees C for 5 h, 700 degrees C for 8 h and
      700 degrees C for 11 h) were used in the production of the Ti-6Al-4V/HA composite
      powders. Results showed that biodissolution followed by apatite precipitation had
      taken place after soaking in SBF. In addition, it was found that consolidation at
      700 degrees C for 5 h resulted in a weak mechanical locking of calcium phosphate
      on the Ti-6Al-4V surfaces; and the formation of small crystallites, which would
      increase the dissolution rate.

PMID- 11336295
TI  - In vitro fatigue behaviour of vacuum plasma and detonation gun sprayed
      hydroxyapatite coatings.
AB  - The fatigue behaviour of vacuum plasma sprayed (VPS) and detonation gun sprayed
      (DGUN) hydroxyapatite coatings on titanium substrates has been compared in air
      and in buffered Ringer's solution. There was an increase in the surface
      microcracking and bulk porosity of both types of coating tested in air. After 1
      million cycles in Ringer's solution the VPS coatings had completely delaminated
      from their substrates. In contrast the DGUN coatings retained their integrity
      when tested up to 10 million cycles but were beginning to show signs of
      delamination at the interface.

PMID- 11336296
TI  - Effect of surface roughness of the titanium alloy Ti-6Al-4V on human bone marrow
      cell response and on protein adsorption.
AB  - The effect of surface roughness of the titanium alloy Ti-6Al-4V (Ti alloy) on the
      short- and long-term response of human bone marrow cells in vitro and on protein
      adsorption was investigated. Three different values in a narrow range of surface
      roughness were used for the substrata (R(alpha): 0.320, 0.490 and 0.874 microm).
      Cell attachment, cell proliferation and differentiation (alkaline phosphatase
      specific activity) were determined past various incubation periods. The protein
      adsorption of bovine serum albumin and fibronectin, from single protein
      solutions, on rough and smooth Ti alloy surfaces was examined with two methods, X
      ray photoelectron spectroscopy (XPS) and radiolabeling. Cell attachment and
      proliferation were surface roughness sensitive and increased as the roughness of
      Ti alloy increased. No statistically significant difference was observed in the
      expression of ALP activity on all three Ti alloy surfaces and culture plastic.
      Both methods, XPS and protein radiolabeling, showed that human serum albumin was
      adsorbed preferentially onto the smooth substratum. XPS technique showed that the
      rough substratum bound a higher amount of total protein (from culture medium
      supplied with 10% serum) and fibronectin (10-fold) than did the smooth one. The
      cell attachment may be explained by the differential adsorption of the two
      proteins onto smooth and rough Ti alloy surfaces.

PMID- 11336297
TI  - Biocompatibility and osteogenesis of refractory metal implants, titanium,
      hafnium, niobium, tantalum and rhenium.
AB  - To evaluate the biocompatibility of refractory metals, titanium, hafnium,
      niobium, tantalum and rhenium were implanted in rats, and histological
      observation and elemental mapping were performed by X-ray scanning analytical
      microscope (XSAM) and electron probe microanalyzer (EPMA). The titanium, hafnium,
      niobium, tantalum and rhenium wires were implanted in the subcutaneous tissue of
      the abdominal region and in femoral bone marrow of rats for either 2 or 4 weeks.
      No inflammatory response was observed around the implants, and all the implants
      were encapsulated with thin fibrous connective tissue. No dissolution of these
      metals was detected by XSAM in the soft tissue. Histological examination of the
      hard tissue showed that the amount of new bone formation decreased slightly from
      the second to the fourth week after implantation, and that the percentage of bone
      in contact with the implant increased markedly over the same period. No
      dissolution of these metals was detected by EPMA in the hard tissue. The Ca and P
      intensities in the mapping images of newly formed bone were higher after 4 weeks
      than those after 2 weeks, which suggests that the newly formed bone continued to
      mature from 2 to 4 weeks after implantation. These results indicate that
      titanium, hafnium, niobium, tantalum and rhenium have good biocompatibility and
      osteoconductivity.

PMID- 11336298
TI  - Oriented Schwann cell growth on micropatterned biodegradable polymer substrates.
AB  - This paper investigates the influence of substrate-mediated chemical and physical
      guidance on the growth and alignment of Schwann cells in vitro. Novel techniques
      were developed to fabricate microgrooves with adsorbed proteins on biodegradable
      polymer substrates made of poly(D,L-lactic acid). Compression molding and solvent
      casting were used to transfer micropatterns from quartz and silicon substrates
      onto biodegradable polymer films. Laminin was selectively adsorbed onto the
      grooves and rat sciatic Schwann cells were seeded on the substrates. Laminin was
      found to improve adhesion of Schwann cells on the substrates. The microgrooves
      were found to cause the Schwann cells to align along the direction of the
      grooves. The groove width influenced Schwann cell alignment the most, while
      groove depth did not seem to play a significant role. The degradation of the
      grooves in the solvent cast films was much slower than those in the compression
      molded films, making them the preferred substrates for Schwann cell culture.

PMID- 11336299
TI  - Poly(lactide-co-glycolide)/hydroxyapatite delivery of BMP-2-producing cells: a
      regional gene therapy approach to bone regeneration.
AB  - Currently, functional treatment of fracture non-unions and bone loss remains a
      significant challenge in the field of orthopaedic surgery. Tissue engineering of
      bone has emerged as a new treatment alternative in bone repair and regeneration.
      Our approach is to combine a polymeric matrix with a cellular vehicle for
      delivery of bone morphogenetic protein-2 (BMP-2), constructed through retroviral
      gene transfer. The objective of this study is to develop an osteoinductive,
      tissue-engineered bone replacement system by culturing BMP-2-producing cells on
      an osteoconductive, biodegradable, polymeric-ceramic matrix. The hypothesis is
      that retroviral gene transfer can be used effectively in combination with a
      biodegradable matrix to promote bone formation. First, we examined the in vitro
      attachment and growth of transfected BMP-producing cells on a PLAGA-HA scaffold.
      Second, the bioactivity of the produced BMP in vitro was evaluated using a mouse
      model. It was found that the polymer-ceramic scaffold supported BMP-2 production,
      allowing the attachment and growth of retroviral transfected, BMP-2-producing
      cells. In vivo, the scaffold successfully functioned as a delivery vehicle for
      bioactive BMP-2, as it induced heterotopic bone formation in a SCID mouse model.

PMID- 11336300
TI  - Effect of convection on osteoblastic cell growth and function in biodegradable
      polymer foam scaffolds.
AB  - Culture of seeded osteoblastic cells in three-dimensional osteoconductive
      scaffolds in vitro is a promising approach to produce an osteoinductive material
      for repair of bone defects. However, culture of cells in scaffolds sufficiently
      large to bridge critical-sized defects is a challenge for tissue engineers.
      Diffusion may not be sufficient to supply nutrients into large scaffolds and
      consequently cells may grow preferentially at the periphery under static culture
      conditions. Three alternative culturing schemes that convect media were
      considered: a spinner flask, a rotary vessel, and a perfusion flow system.
      Poly(DL-lactic-co-glycolic acid) (PLGA) foam discs (12.7 mm diameter, 6.0 mm
      thick, 78.8% porous) were seeded with osteoblastic marrow stromal cells and
      cultured in the presence of dexamethasone and L-ascorbic acid for 7 and 14 days.
      Cell numbers per foam were found to be similar with all culturing schemes
      indicating that cell growth could not be enhanced by convection, but histological
      analysis indicated that the rotary vessel and flow system produced a more uniform
      distribution of cells throughout the foams. Alkaline phosphatase (ALP) activity
      per cell was higher with culture in the flow system and spinner flask after 7
      days, while no differences in osteocalcin (OC) activity per cell were observed
      among culturing methods after 14 days in culture. Based on the higher ALP
      activity and better cell uniformity throughout the cultured foams, the flow
      system appears to be the superior culturing method, although equally important is
      the fact that in none of the tests did any of the alternative culturing
      techniques underperform the static controls. Thus, this study demonstrates that
      culturing techniques that utilize fluid flow, and in particular the flow
      perfusion system, improve the properties of the seeded cells over those
      maintained in static culture.

PMID- 11336301
TI  - Surface characterization of porous, biocompatible protein polymer thin films.
AB  - Genetically engineered protein polymer coatings are intended to improve the
      performance of implantable neural prosthetic devices. To facilitate device
      integration with tissue, three-dimensionally structured protein polymer films
      were deposited on the devices using electrostatic atomization and gas-evolution
      foaming. Periodic features and the length-scale dependence of the surface
      roughness were identified in topographic data collected using scanning probe
      microscopy. Using the power spectral density of surface data, the influence of
      process parameters on the surface roughness of protein polymer thin films was
      examined. Details of surface topography are known to influence biological
      behavior, and the method presented was capable of quantifying the evolution of
      surface features at biologically relevant length scales. This study provides a
      means for the quantitative exploration of the effects of topography on the
      performance of these devices and on biocompatibility in general.

PMID- 11336302
TI  - The effects of alginate composition on encapsulated betaTC3 cells.
AB  - The effects of alginate composition on the growth of murine insulinoma betaTC3
      cells encapsulated in alginate/poly-L-lysine/alginate (APA) beads, and on the
      overall metabolic and secretory characteristics of the encapsulated cell system,
      were investigated for four different types of alginate. Two of the alginates used
      had a high guluronic acid content (73% in guluronic acid residues) with varying
      molecular weight, while the other two had a high mannuronic acid content (68% in
      mannuronic acid residues) with varying molecular weight. Each composition was
      tested using two different polymer concentrations. Our data show that betaTC3
      cells encapsulated in alginates with a high guluronic acid content experienced a
      transient hindrance in their metabolic and secretory activity because of growth
      inhibition. Conversely, betaTC3 cells encapsulated in alginates with a high
      mannuronic acid content experienced a rapid increase in metabolic and secretory
      activity as a result of rapid cell growth. Our data also demonstrate that an
      increase in either molecular weight or concentration of high mannuronic acid
      alginates did not alter the behavior of the encapsulated betaTC3 cells.
      Conversely, an increase in molecular weight and concentration of high guluronic
      acid alginates prolonged the hindrance of glucose metabolism, insulin secretion
      and cell growth. These observations can be best interpreted by changes in the
      microstructure of the alginate matrix, i.e., interaction between the contiguous
      guluronic acid residues and the Ca2+ ions, as a result of the different
      compositions.

PMID- 11336303
TI  - Chemically coupled hydroxyapatite-polyethylene composites: structure and
      properties.
AB  - Silanation of hydroxyapatite and acrylic acid grafting of polyethylene were
      employed to improve bonding between hydroxyapatite and polyethylene. The
      structure and properties of chemically coupled hydroxyapatite reinforced high
      density polyethylene (HA/HDPE) composites were subsequently investigated using
      various techniques. It was shown that there existed a silicon-containing
      interphase between the hydroxyapatite particle and the polyethylene matrix. The
      silane coupling agent used promoted chemical adhesion between hydroxyapatite
      particles and the polymer. The use of the silane coupling agent also facilitated
      the penetration of polymer into cavities in individual ceramic particles, which
      resulted in enhanced mechanical interlocking at the matrix-reinforcement
      interface. With a strong bond (both mechanical and chemical) being formed between
      hydroxyapatite and polyethylene, chemically coupled HA/HDPE composites possessed
      improved mechanical properties and fracture behaviour.

PMID- 11336304
TI  - Evaluation of the effect of seven acrylic bone cements on erythrocytes and
      plasmatic phase of coagulation.
AB  - The haemolytic activity and the effect on the plasmatic phase of coagulation of
      seven bone cements were evaluated (Sulfix-60 from Sulzer Orthopedic Inc., a bone
      cement at low viscosity from Zimmer, a bone cement dough-type from Zimmer,
      Palacos R from Merck, CMW1, CMW2 and CMW3 from DePuy International Ltd.).
      Haemolytic activity was tested by adding the cement extracts in phosphate
      buffered saline to a suspension of erythrocytes. After 4 h incubation at 37
      degrees C, the haemoglobin concentration was determined on the supernatants by
      colorimetric method. The effect on the plasmatic phase of coagulation was tested
      by adding the cement extracts in saline to human plasma. After 30 min incubation
      at room temperature activated partial thromboplastin time (APTT) was determined.
      All extracts induced non-significant variations of haemoglobin concentration and
      APTT. It was concluded that the tested cement extracts do not induce haemolysis
      and do not activate the intrinsic pathway of coagulation, at least in the tests
      that were performed.

PMID- 11336305
TI  - Enhanced osteoclast-like cell functions on nanophase ceramics.
AB  - Synthesis of tartrate-resistant acid phosphatase (TRAP) and formation of
      resorption pits by osteoclast-like cells, the bone-resorbing cells, on nanophase
      (that is, material formulations with grain sizes less than 100nm) alumina and
      hydroxyapatite (HA) were investigated in the present in vitro study. Compared to
      conventional (that is, grain sizes larger than 100 nm) ceramics, synthesis of
      TRAP was significantly greater in osteoclast-like cells cultured on nanophase
      alumina and on nanophase HA after 10 and 13 days, respectively. In addition,
      compared to conventional ceramics, formation of resorption pits was significantly
      greater by osteoclast-like cells cultured on nanophase alumina and on nanophase
      HA after 7, 10, and 13 days, respectively. The present study, therefore,
      demonstrated, for the first time, enhanced osteoclast-like cell function on
      ceramic surfaces with nanometer-size surface topography.

PMID- 11336306
TI  - Poly n-butyl cyanoacrylate nanoparticles: a mechanistic study of polymerisation
      and particle formation.
AB  - Poly n-butyl cyanoacrylate has been used in the synthesis of nanoparticles by
      dispersion polymerisation in aqueous media. Following establishment of a
      thermometric procedure for assessment of monomer reactivity, the relationships
      between monomer-polymer conversion reactions and particle development at various
      pH values was investigated. Particle size was measured during the synthesis
      process using a laser diffraction technique and final particle character was
      assessed by scanning electron microscopy. Optimum conditions for particle
      production were a dispersion medium of pH 2.5 at a temperature of 65 degrees C,
      with dextran 70 used as a steric stabiliser. In the presence of dextran,
      following a period of equilibration, colloidally stable particles form, but in
      the absence of dextran particles are colloidally unstable and rapidly coalesce.
      Measurement of molecular weight changes through the synthesis process show an
      upward shift consistent with the initial formation of oligomers, which then
      further polymerise through a re-initiation re-polymerisation process until an
      equilibrium molecular weight is reached.

PMID- 11336307
TI  - EGF containing gelatin-based wound dressings.
AB  - In case of bulk loss of tissue or non-healing wounds such as burns, trauma,
      diabetic, decubitus and venous stasis ulcers, a proper wound dressing is needed
      to cover the wound area, protect the damaged tissue, and if possible to activate
      the cell proliferation and stimulate the healing process. In this study,
      synthesis of a novel polymeric bilayer wound dressing containing epidermal growth
      factor (EGF) -loaded microspheres was aimed. For this purpose, a natural,
      nontoxic and biocompatible material, gelatin, was chosen as the underlying layer
      and various porous matrices in sponge form were prepared from gelatin by freeze
      drying technique. As the external layer, elastomeric polyurethane membranes were
      used. Two different doses of EGF was added into the prepared gelatin sponges (1
      and 15 microg/cm2) to activate cell proliferation. EGF addition was carried out
      either in free form or within microspheres to achieve prolonged release of EGF
      for higher efficiency. The prepared systems were tested in in vivo experiments on
      full-thickness skin defects created on rabbits. At certain intervals, wound areas
      were measured and tissues from wound areas were biopsied and processed for
      histological examinations. The wound areas decreased upon low-dose EGF
      application but the difference between the affects of free EGF and microsphere
      loaded EGF was not so distinct. Upon increasing the dose of EGF by a factor of
      15, it was observed that controlled release of EGF from microspheres provided a
      higher degree of reduction in the wound areas. Histological investigations showed
      that the prepared dressings were biocompatible and did not cause any mononuclear
      cell infiltration or foreign body reaction. The structure of the newly formed
      dermis was almost the same as that of the normal skin.

PMID- 11336308
TI  - Elastic and plastic behavior of plasma-sprayed hydroxyapatite coatings on a Ti
      6Al-4V substrate.
AB  - A novel approach that combines the indentation tests with nonlinear finite
      element modeling (FEM) is proposed to estimate the elastic/plastic constitutive
      relation of plasma-sprayed hydroxyapatite (HA) coatings on a Ti-6Al-4V substrate.
      The Ramberg-Osgood constitutive equation can well describe the deformation
      behavior of plasma-sprayed HA coating on Ti-6Al-4V. A reasonable estimation for
      the elastic modulus of the HA coatings is given, based on the fact that the
      coating consists of a crystalline phase, an amorphous phase and pores. The
      Ramberg-Osgood equations of the coatings indicate that the post-treatment
      increases both resistance to elastic and plastic deformation, but no effect on
      strain hardening behavior. The post-treatment, however, could reduce the
      resistance to coating/substrate separation. The influence of titanium substrate
      becomes more significant with decreasing coating thickness and increasing
      indentation load because the plasma-sprayed HA coatings exhibit much less
      resistance to indentation deformation than does Ti-6Al-4V.

PMID- 11336309
TI  - Porosity-graded hydroxyapatite ceramics to replace natural bone.
AB  - Porous hydroxyapatite HA bodies were prepared with an aim to simulate bone tissue
      morphology. By varying the characteristics of starting HA powders and the
      impregnation strategy of cellulosic sponges with rheologically optimized
      slurries, a wide range of physico-chemical and mechanical properties of the
      porous ceramics can be obtained. The samples were characterized
      microstructurally, by density and porosimetry and by mechanical strength.
      Cylindrical specimens exhibiting a porosity gradient showed a promising behaviour
      after implantation in rabbits' femur: newly formed bone grew in tight contact
      with the ceramic in a very short time, no modified cells are induced and bone
      tissue fills even the inner pores.

PMID- 11336310
TI  - Biodegradable microspheres of novel segmented poly(ether-ester-amide)s based on
      poly(epsilon-caprolactone) for the delivery of bioactive compounds.
AB  - A novel class of multiblock poly(epsilon-caprolactone)-based polymers containing
      hydrophilic trioxyethylene segments and potentially relevant to the delivery of
      drugs is described in this work. L-phenylalanine residues may also be inserted
      into the hydrophilic blocks to generate peptide bonds susceptible to enzymatic
      attack. The investigated polymers were poly(ether-ester-amide)s (PEEAs) obtained
      by a two-step polymerization procedure from OH-end capped low molecular weight
      poly(epsilon-caprolactone), sebacoyl chloride and either 4,7,10-trioxa-1,13
      tridecanediamine (PEEA1) or 1,13-di(L-phenylalaninamido)-4,7,10-trioxatridecane
      (PEEA2). PEEAs were characterized by 1H-NMR spectroscopy, differential scanning
      calorimetry, gel permeation chromatography and were tested for their suitability
      in producing microspheres. Particles obtained by the single emulsion-solvent
      evaporation technique were regular and smooth (SEM analysis) showing a monomodal
      distribution of dimensions. To assess the potentiality of PEEAs in the oral
      delivery of drugs, three model compounds with different pKa and solubilities-
      diclofenac, nicardipine and dicumarol--were encapsulated within PEEA
      microspheres. For the sake of comparison, microspheres prepared from poly(epsilon
      caprolactone) (PCL) with a molecular weight similar to PEEAs were also prepared
      and tested. The release of diclofenac from all the microspheres was very rapid
      (100% released within 2 h) whereas nicardipine release was slower and biphasic.
      The initial phase approximated a near zero-order release, being the fraction of
      nicardipine released after 8 h from PEEA microspheres higher with respect to PCL
      particles (about 70 vs. 30%). This result was ascribed to the lower crystallinity
      of PEEAs with respect to PCL which results in a facilitated access of water
      molecules through the polymer matrix. The lipophilic-unionizable dicumarol was
      released from PEEA microspheres at a very slow rate. Therefore, dicumarol-loaded
      PEEA2 microspheres allowed the study of the influence on the release rate of the
      insertion into the polymer chain of enzymatically degradable bonds. PEEA2
      microspheres released dicumarol at the same rate in a medium with or without the
      proteolitic enzyme alpha-chymotrypsin. Although the insertion of an isolated
      amino acid was not sufficient to confer enzyme susceptibility to the polymer, the
      distinctive properties of PEEAs make their use very attractive in the field of
      controlled release.

PMID- 11336311
TI  - Stress relaxation in titanium-ceramic beams during veneering.
AB  - Spalling of a ceramic from the metallic substrate is related to stress at the
      metallo-ceramic interface of crowns. The purpose of this study is to (1)
      establish a method for recording the bending radius of metallo-ceramic strips
      during cooling, (2) calculate the stress in the metal adjacent to the metallo
      ceramic interface based on the recorded bending and (3) compare this stress with
      that calculated from the mismatch between measurements of the coefficients of
      thermal expansion, alpha, of the ceramic and titan. Metallo-ceramic specimens (n
      = 9) were made by firing a 0.6 mm thick layer of ceramic on (11.3 x 3.2 x 0.6) mm
      Ti-substrates. The opaque material of three commercial porcelains for titanium
      were applied: Titankeram (Vita), TiBond (DeTrey/Dentsply) and Duceratin (Ducera).
      The Ti-side of the specimens rested on two quartz supports of a jig in an
      apparatus for thermo-mechanical analysis (TMA). The vertical, mid-span movements
      of a quartz flexure probe resting on the ceramic-side of the metallo-ceramic
      specimen were continuously recorded during heating and cooling in the temperature
      range 20-600 degrees C. The cooling rate was 6 degrees C min(-1) from 600 degrees
      C, to below the glass transition temperature, Tg. The bending radii recorded
      continuously during cooling were reproducible. The thermal expansions,
      alpha(cer), lay in the range 23-47 x 10(-6) K(-1) above Tg compared to 7.9-9.8 x
      10(-6) K(-1) (alpha(cer, 20-400 degrees C)) below Tg. For Ti, the coefficient of
      thermal expansion was found to be 9.7 x 10(-6) K(-1) (alpha(Ti, 20-600 degrees
      C)). The calculated stresses above Tg based on the thermal mismatch were much
      higher than those calculated from the flexure movement. The observed differences
      are attributed to stress relaxations in the ceramic above Tg.

PMID- 11336312
TI  - Repetitive subcutaneous implantation of different types of (biodegradable)
      biomaterials alters the foreign body reaction.
AB  - In the present study two biodegradable materials (cross-linked collagens) and two
      non-biodegradable materials (polyurethane and silicone) were applied in a
      repetitive subcutaneous implantation model in rats. In contrast to the first
      challenge, the second challenge with the same type of material, but at a
      different subcutaneous site of the same animal, induced an increase of
      macrophages and giant cells inside the biodegradable materials. Additionally,
      only after the second challenge clusters and accumulations of plasma cells were
      present in the surrounding tissue of each type of material. In the same areas an
      increase of MHC II expression was measured by immunocytochemistry. Differences in
      the numbers of macrophages and T cells were not observed around the explants.
      Undifferentiated B cells or NK cells were not present at any time point. The
      results indicate that alterations observed after the second challenge did not
      depend on biodegradation of the materials. Significance of these findings should
      be considered in view of increased and repetitive use of the same type of
      biomaterial (possibly for different application sites) for implantation in
      patients.

PMID- 11336313
TI  - Adsorption and release studies of sodium ampicillin from hydroxyapatite and glass
      reinforced hydroxyapatite composites.
AB  - As a potential therapy for periodontitis, sodium ampicillin, a broad spectrum
      antibiotic, was adsorbed onto hydroxyapatite (HA) and glass-reinforced
      hydroxyaptite (GR-HA) composites, and was subsequently released in vitro. The
      sodium ampicillin, was adsorbed more on HA compared to the GR-HA composites. X
      ray diffraction (XRD) and Rietveld analysis were used to identify and quantify
      the levels of HA and beta-tricalcium phosphate (beta-TCP) in the microstructure
      of the GR-HA composites. Lattice parameters changes were observed for the beta
      TCP phase dependant on the amount of glass added. The release kinetics were shown
      to be divided into three stages, the first of which where a large amount of
      sodium ampicillin is released, followed by a slower release rate and then a final
      stage where the release amount approaches zero, until no more sodium ampicillin
      was present. X-ray photoeletron spectroscopy (XPS) studies were carried out in
      order to ensure that the entire antibiotic adsorbed onto the materials had been
      released. These kinetics studies have indicated the possibility of using these
      materials as possible carriers for drug delivery.

PMID- 11336314
TI  - A preliminary comparison of the mechanical properties of chemically cured and
      ultrasonically cured glass ionomer cements, using nano-indentation techniques.
AB  - There is a requirement for a dental cement with properties comparable or superior
      to conventional glass ionomer cements (GICs) but with the command set properties
      of the resin-modified GICs. The objective of this work was to show that the
      application of ultrasound to conventional Fuji IX commercial glass ionomer cement
      imparts a command set, whilst improving the short-term surface mechanical
      properties. Nano-indentation techniques were employed to highlight the
      improvements in hardness and creep resistance imparted to the cement through the
      application of ultrasound. The instant set imparted by the application of
      ultrasound provides improved surface hardness and creep, particularly within the
      first 24 h after setting. The surface hardness of the chemically cured Fuji IX
      (176 M Pa) increased by an order of magnitude when set ultrasonically (2620 M
      Pa), whilst creep reduced to a negligible amount. Rapid setting allows for
      shorter chair time and an improved clinical technique, making restorations more
      convenient for both the patient and clinician.

PMID- 11336315
TI  - A new in vivo model for testing cartilage grafts and biomaterials: the 'rabbit
      pinna punch-hole' model.
AB  - In this study an animal model was developed for evaluation of the feasibility of
      cartilage grafts. In the cartilage of the external ear of the rabbit multiple
      holes, 6 mm in diameter, were punched, leaving the adherent skin intact.
      Different experimental groups were evaluated. First, the punch-hole model was
      validated under various conditions to study spontaneous or perichondrial
      initiated regeneration of the cartilage defect. When both cartilage and
      perichondrium was excised no spontaneous repair of the cartilage defect was
      observed. When perichondrium is present, variable patch-like closure of the punch
      hole was found. As 'golden standard' a punched out piece of cartilage was
      reimplanted directly. This condition showed adequate closure of the punch hole,
      however, no perfect integration of graft and surrounding cartilage was observed.
      Secondly, to evaluate the 'punch-hole model' a biomaterial, trabecular
      demineralized bovine bone matrix (DBM), was implanted and tested as a scaffold
      for tissue engineering techniques in vivo and in vitro. Direct implantation of
      DBM did not lead to any cartilage formation to close the defect. In vivo
      engineered cartilage, generated by enveloping DBM in perichondrium for 3 weeks,
      could adequately close the punch hole. When DBM was seeded with isolated
      chondrocytes in vitro before implantation in the defect, a highly fragmented
      graft, with some islets of viable cells was seen. To promote an efficient and
      reliable evaluation of cartilage grafts a semi-quantitative grading system was
      developed. Items such as quality, quantity and integrity of the cartilage graft
      were included in a histomorphological grading system to provide information about
      the properties of a specific cartilage graft. To validate the grading system, all
      conditions were scored by two independent observers. An excellent reliability (R
      = 0.96) was seen between the observers. In summary, the rabbit pinna punch-hole
      model is a reliable and efficient method for first evaluation of cartilage
      grafts. The results can be easily analyzed using a semi-quantitative grading
      system.

PMID- 11336316
TI  - Functional assessment and tissue response of short- and long-term absorbable
      surgical meshes.
AB  - Within the last few years meshes have become essential for the temporary closure
      of the abdominal cavity to avoid the development of an intra-abdominal
      compartment syndrome. The interposition of a mesh as an inlay reduces the intra
      abdominal pressure and improves markedly the blood circulation, particularly for
      the intestines and kidneys. Whereas non-absorbable meshes usually tend to produce
      fistulas in direct contact to the bowels, the interposition of short-term
      absorbable meshes result in large incisional hernias in almost all cases. In the
      following study we investigated the functional and histological consequences of a
      short-term absorbable mesh (polyglactin 910, Vicryl, loss of 50% of its
      mechanical stability within 3 weeks) and a long-term absorbable mesh
      (polylactide, LTS, preserved >50% of its mechanical stability for over 1 year).
      The mesh-modifications were both tested with the aid of three-dimensional
      stereography, tensiometry, light- (LM) and transmission electron microscopy (TEM)
      as well as morphometry after implantation intervals of 3, 7, 14, 21, 45, 90, 135
      and 180 days in a standardised rat model. The PG-mesh initially revealed a
      pronounced inflammatory reaction and a significantly increased formation of
      connective tissue. The extensive arrangement of connective tissue in the
      interface mesh/recipient tissues correlated to an increased stiffness of the
      abdominal wall compared to the sham-group. However, a loss of mechanical
      stability and an increase of elasticity could be detected after 3 weeks of
      implantation which may be explained by the rapid absorption of the mesh material.
      In contrast to PG, the LTS-mesh indicated a decreased but persisting inflammatory
      reaction in the interface mesh-fibres/recipient tissues and a significantly
      reduced induction of connective tissue. Although, the formation of scar-tissue
      was diminished compared to PG the LTS-mesh preserved its mechanical stability
      after 180 days. The results indicate that the frequent development of incisional
      hernias with short-term absorbable meshes (PG) might be due to the decreased
      mechanical stability and dilatation of the newly formed connective tissue after 2
      3 weeks. Moreover, extensive scar tissue development may promote adhesion
      formation. The implantation of the long-term absorbable LTS-mesh seems to be
      favourable with respect to its long-term mechanical stability and the decreased
      connective tissue formation.

PMID- 11336317
TI  - Preparation and characterisation of titania/hydroxyapatite composite coatings
      obtained by sol-gel process.
AB  - In the present work a titania network encapsulating a hydroxyapatite particulate
      phase is proposed as a bioceramic composite coating. The coating on a titanium
      substrate was produced starting from a sol containing a mixture of titania
      colloidal particles and hydroxyapatite submicron particles using the dip-coating
      technique. The microstructure, the morphology and the surface chemical
      composition of the coating were characterised using X-ray diffraction (XRD),
      scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS),
      respectively. Adhesion tests were also performed. These analyses showed that the
      obtained coating was chemically clean, homogeneous, rough, porous, with a low
      thickness and well-defined phase composition as well as a good adhesion to the
      substrate.

PMID- 11336318
TI  - Age-hardening reactions in a type III dental gold alloy.
AB  - The age-hardening reactions in a commercial type III dental gold alloy were
      studied by means of hardness test, X-ray diffraction study and scanning and
      transmission electron microscopic observations. The hardening was attributed to
      the formation of the metastable AuCu 1' type ordered phase in the grain interior
      by the isothermal ageing at 225 and 450 degrees C at which two hardness peaks
      were observed by the isochronal ageing. By ageing at 450 degrees C, the hardening
      did not begin immediately because the incubation period was required. The age
      hardening at 225 degrees C was characterized by a slow growth rate of the
      metastable AuCu 1' type ordered phase. The overageing with softening which
      occurred following prolonged ageing at 450 degrees C was due to the formation of
      the lamellar structure composed of the Ag-rich alpha1 and AuCu 1 type ordered
      phases at grain boundaries.

PMID- 11336319
TI  - Antithrombotic and fibrinolytic system of human endothelial cells seeded on PTFE:
      the effects of surface modification of PTFE by ammonia plasma treatment and ECM
      protein coatings.
AB  - The aim of this study was to determine the effects of ECM protein coatings and
      surface modification of PTFE on the ability of seeded human endothelial cells
      (EC) to secrete prostacyclin (PGI2), plasminogen inhibitor-1 (PAI-1) and tissue
      plasminogen activator (t-PA). PTFE surfaces were modified by a novel surface
      modification technique based on ammonia plasma. Fibronectin, collagen type-1 and
      gelatin-coated ammonia plasma modified PTFE and unmodified PTFE surfaces were
      employed and compared in this study. All ammonia plasma modified surfaces showed
      similar secretions of PGI2 compared to non-modified PTFE surfaces. With the
      exception of gelatin-coated modified PTFE, seeded EC seeded on all modified PTFE
      showed lower levels of PAI-1 secretion compared to those seeded on unmodified
      PTFE. The specific activity of t-PA secreted by EC seeded on ammonia plasma
      modified and fibronectin coated modified PTFE showed increases of 100 and 30%,
      respectively, when compared to their unmodified counterparts. Our studies show
      that EC seeded on modified PTFE have ability to secrete PGI2 that modulates the
      early phase of thrombus formation. Furthermore, superior t-PA profile, along with
      lower levels of PAl-1 suggest that ammonia plasma modification and use of
      appropriate ECM proteins can modulate antithrombotic and fibrinolytic properties
      of in vitro endothelialized vascular prostheses. Accordingly, these surfaces may
      be suitable to further develop protocols and other strategies for arterial and
      venous reconstruction.

PMID- 11336320
TI  - Phase I studies of cisplatin and docetaxel administered by three consecutive
      weekly infusions for advanced non-small cell lung cancer in elderly and non
      elderly patients.
AB  - BACKGROUND: To determine the maximum tolerated dose and recommended dose of
      cisplatin and docetaxel administered by three consecutive weekly infusions in
      both non-elderly (< or =74 years) and elderly (> or =75 years) patients, we
      conducted two independent phase I studies for nonelderly and elderly patients
      with non-small cell lung cancer. METHODS: Between April 1998 and September 1999,
      26 non-elderly (median, 54 years; range, 44-73 years) and 12 elderly (median, 76
      years; range, 75-80 years) patients with non-small cell lung cancer were entered
      in these studies. The eligibility criteria of both cohorts were identical except
      for age. Chemotherapy consisted of cisplatin 25 mg/m2 and an escalated dose of
      docetaxel on days 1, 8 and 15 every 4 weeks. The initial dose of docetaxel was 20
      mg/m2 and it was increased by 5 mg/m2 at each dose level. RESULTS: In the non
      elderly and elderly cohorts, up to 45 or 25 mg/m2 of docetaxel, respectively,
      were administered. Dose-limiting toxicities were neutropenia, liver damage,
      pneumonia and omission of treatment on day 15 by leukopenia and refusal in the
      non-elderly cohort; pneumonia and omission of treatment on day 15 by refusal due
      to fatigue/asthenia or fever in the elderly cohort. We considered the recommended
      doses for phase II studies were cisplatin 25 mg/m2 and docetaxel 35 mg/m2 on days
      1, 8 and 15 for non-elderly patients and cisplatin 25 mg/m2 and docetaxel 20
      mg/m2 on days 1, 8 and 15 for elderly patients. Seven of 26 (27%) and seven of 12
      (58%) patients achieved a partial response, median survival times were 8.7 and
      7.2 months and 1 year survival rates were 27 and 27% in the non-elderly and
      elderly cohorts, respectively. CONCLUSIONS: Further evaluation of this
      combination chemotherapy is warranted for both nonelderly and elderly patients
      with non-small cell lung cancer but the dose of docetaxel should be lower for
      elderly than non-elderly patients.

PMID- 11336321
TI  - Is preventive resection of the extrahepatic bile duct necessary in cases of
      pancreaticobiliary maljunction without dilatation of the bile duct?
AB  - BACKGROUND: No consensus has been reached on whether preventive resection of the
      extrahepatic bile duct is necessary in cases of pancreaticobiliary maljunction
      (PBM) without dilatation of the extrahepatic bile duct (undilated type). METHODS:
      Sixty-eight patients with PBM underwent corrective surgery and several clinical
      characteristics and pathological findings including K-ras point mutation were
      evaluated. RESULTS: Unlike dilated bile duct, none of the patients with undilated
      type duct had clinical symptoms in early childhood. In patients with either
      cystic or spindle type duct, amylase levels in the bile duct were >10(4) U/l,
      whereas those in patients with undilated type duct were <10(4) U/l. Postoperative
      scintigraphy of the biliary system of undilated type revealed no evidence of
      cholestasis. After surgery, eight patients with undilated type duct, in whom the
      bile duct had been preserved, had no further clinical symptoms and no evidence of
      malignancy. Bile duct tissue specimens revealed no hyperplasia, dysplasia or
      cancerous lesions and they had no K-ras mutation in undilated type. CONCLUSION:
      The results showed that there was little bile stasis, injury to the mucosa was
      mild and less genetic changes could be seen in patients with undilated type duct.
      Therefore, in patients without dilatation of bile duct and advanced cancer,
      cholecystectomy alone is sufficient.

PMID- 11336322
TI  - Papillary carcinoma of the thyroid with distant metastases to the cerebrum: a
      case report.
AB  - Cerebral metastases from papillary carcinoma of the thyroid are a very uncommon
      condition, but such metastases behave more aggressively and show poor prognosis.
      These metastases almost always involve concomitant lung or bone metastases which
      may be the first metastatic sites. Here we report a 53-year-old man with diffuse
      goiter and cervical lymphadenopathy who developed symptoms of elevated
      intracranial pressure. Computed tomography demonstrated ring-enhanced lesions
      showing a severe mass effect in the right cerebrum and a nodule in the right
      thyroid gland accompanied by swollen lymph nodes. Biopsied specimens of the
      thyroid nodule demonstrated malignant cells of papillary carcinoma. Surgical
      excision of the metastatic brain lesions was followed by total thyroidectomy with
      regional lymphadenectomy. Histological examinations confirmed that the patient
      had cerebral metastases from papillary carcinoma of the thyroid without other
      distant metastasis. Neurological abnormality disappeared after surgery and
      treatment with radioactive iodine (131I) and oral thyroxine were initiated
      thereafter. This case suggests that the thyroid gland is potentially a primary
      source of metastatic brain carcinoma. Moreover, early detection of cerebral
      metastases is crucial because these metastatic lesions can be life threatening,
      in contrast to the relatively less severe clinical course of this malignancy
      unless it is associated with any distant metastasis.

PMID- 11336323
TI  - Small cell lung cancer with a brain metastasis controlled for 5 years: a case
      report.
AB  - We report a case of small cell lung cancer whose initial presentation was a
      solitary brain metastasis. On chest radiography the primary tumor was unclear and
      only detected by bronchofiberscopy. A small single pulmonary metastasis was noted
      in the right lower lobe. Subtotal resection and external irradiation were applied
      to the brain tumor and external irradiation was applied to the lung. Concurrently
      one course of systemic chemotherapy was administered. The tumors in the brain and
      lung had disappeared by the end of the treatment. The patient has been alive and
      well for 5 years without recurrence.

PMID- 11336324
TI  - Hepatocellular carcinoma with Pancoast's syndrome as an initial symptom: a case
      report.
AB  - Pancoast's syndrome refers to a condition consisting of Horner's syndrome and arm
      pain that is most commonly found in patients with a lung tumor of the superior
      sulcus invading the upper ribs or spine, lower brachial plexus and sympathetic
      chain. We report a 76-year-old female who had a thoracic inlet mass that
      presented as Pancoast's syndrome, showing profound pain, numbness and weakness of
      the left upper limb. Further evaluation revealed an increased level of serum
      alpha-fetoprotein (24278 ng/ml), cryptogenic liver cirrhosis and primary
      hepatocellular carcinoma with protruding T3 vertebra metastasis that resulted in
      Pancoast's syndrome. To our knowledge, it is a rare case and only one case has
      been reported previously.

PMID- 11336325
TI  - Usefulness of magnetic resonance imaging for surgical management of extravasation
      of an antitumor agent: a case report.
AB  - We report a case of extravasation of an antitumor agent by preoperative magnetic
      resonance (MR) imaging. MR studies demonstrated a decreased signal intensity on
      T1- and T2-weighted images and a strong enhancement of contrast media in injured
      tissue, including subcutaneous adipose tissue and deep fascia, which was
      cicatrical macroscopically. The MR findings were in good agreement with the
      macroscopic findings. We believe that MR imaging is useful for estimating deep
      tissue damage due to extravasation of an antitumor agent.

PMID- 11336326
TI  - A novel germline mutation of the MEN1 gene, L259del, in a patient with sporadic
      multiple endocrine neoplasia type 1 (MEN1).
AB  - A Japanese woman was treated for insulinoma when she was 29 years old. Ten years
      later, heperparathyroidism and non-functioning adrenal tumor were found and she
      was diagnosed as having multiple endocrine neoplasia type 1 (MEN1). No other
      family members have developed MEN-related lesion(s). Genomic DNA of the patient
      was analyzed by sequencing for the MEN1 gene and a novel, three-base in-frame
      deletion resulting in deletion of an amino acid Leu259 was identified. Her two
      children showed a wild-type sequence at this codon.

PMID- 11336327
TI  - Bladder cancer mortality rates by prefectures in Japan.

PMID- 11336328
TI  - Phase I and pharmacological study of paclitaxel given over 3 h with cisplatin for
      advanced non-small cell lung cancer.
AB  - BACKGROUND: To establish the toxicities and maximum tolerated dose of paclitaxel
      given over 3 h in combination with cisplatin, to determine the pharmacokinetic
      profiles of these two drugs and to observe their antitumor activity, we conducted
      a combination phase I study in non-small cell lung cancer. METHODS: Patients
      received paclitaxel doses of 150-210 mg/m2 given over 3 h and cisplatin doses of
      60-80 mg/m2 as a 1 h infusion 2 h after the end of the paclitaxel infusion.
      RESULTS: A total of 25 patients with previously untreated non-small cell lung
      cancer were enrolled. Granulocytopenia was the most frequent hematological
      toxicity and the most prominent non-hematological toxicity was sensory dominant
      neuropathy. Two of six patients experienced dose limiting toxicities (leukopenia,
      infection and neuropathy) at a dose of paclitaxel 210 mg/m2 and cisplatin 60
      mg/m2, which was considered the maximum tolerated dose. There were seven partial
      responses among 24 evaluable patients, for an overall response rate of 29%. The
      median survival time was 341 days and the 1 year survival rate was 45.8%. As the
      paclitaxel pharmacokinetic parameters in this study were consistent with those of
      our previous single agent study, we found no significant drug-drug interaction
      between the 3 h infusion paclitaxel and cisplatin. CONCLUSION: The recommended
      doses for further study are determined to be paclitaxel 180 mg/m2 and cisplatin
      80 mg/m2. This is a well-tolerated and active regimen for non-small cell lung
      cancer. In view of the promising survival outcome, further evaluation in
      prospective randomized trials versus other regimens is warranted.

PMID- 11336329
TI  - The state-of-the-art in the analysis of estrogenic mycotoxins in cereals.
AB  - The increasing public awareness of chemicals that mimic or otherwise interfere
      with the activity of natural hormones - so-called endocrine disrupters - has also
      led to greater study of mycotoxins with estrogenic potential. The purpose of this
      paper is to introduce the topic of estrogenic mycotoxins and to discuss the state
      of-the-art in the analysis of these substances in cereals, with special emphasis
      on zearalenone (ZON) as its most relevant representative. Because the use of
      immunoaffinity columns (IAC) followed by high-performance liquid chromatography
      with fluorescence detection (HPLC-FLD) and immunoassays are currently the most
      frequently used methods for the determination of ZON and its metabolites, these
      techniques are discussed in more detail. Recent papers, which have revealed the
      great potential of HPLC-MS(MS) for the simultaneous detection and identification
      of several estrogenic mycotoxins, are discussed. The performances of the state-of
      the-art methods are finally compared by study of the results obtained in recent
      international intercomparison studies. On the one hand, these studies revealed
      the good performance of both chromatographic and antibody-based methods. On the
      other hand, the need for better means of external quality assurance measures,
      especially the availability of certified reference materials and certified
      standards, has clearly been demonstrated.

PMID- 11336330
TI  - Nanosphere-antibody conjugates with releasable fluorescent probes.
AB  - Surface-functionalized, probe-containing, polymeric nanospheres with diameters
      between 10 nm and 40 nm (depending on the probe) were used to provide a
      fluorescent endpoint for nonextractive immunoassay. The probes inside the
      nanospheres were lanthanoid ions. Methyl methacrylate was used as the monomer to
      reduce random adsorption of proteins onto the nanosphere surfaces. The acid-group
      surface functionalization allowed the nanospheres to be conjugated to the amine
      groups on the antibodies (IgG). The surfaces were further functionalized with
      alcohol and ester groups to improve the suspension characteristics of the
      nanospheres. As many as four probe ions may be quantified simultaneously,
      although only three with a single ligand. Co-measurement of four probes required
      a combination of two ligands. The intensity of the fluorescence produced by these
      complexes allows detection with a sensitivity equivalent to enzyme-linked
      immunoassay.

PMID- 11336331
TI  - Detection of complement C1-inhibitor with a piezoelectric immunosensor.
AB  - A novel piezoelectric immunosensor has been developed for the detection of human
      complement C1-inhibitor. Anti-C1-inhibitor antibody was immobilized onto the gold
      electrodes of a 9 MHz AT-cut piezoelectric crystal. Coating the crystal with
      polyethyleneimine adhesion, followed by a glutaraldehyde cross-linking method to
      immobilize antibody showed better results than the physical adsorption method
      with respect to sensitivity and reproducibility. Under the optimized experimental
      conditions, the sensor showed good response to the C1-inhibitor in the range from
      2.0 x 10(-8) to 1.2 x 10(-6) g. Other proteins in human serum did not remarkably
      interfere with the detection. The crystals could be regenerated 5 times, when
      bound materials on the crystal surface were eluted by strong acid and strong
      alkali solution and subsequently cleaned in an ultrasonic cleaner.

PMID- 11336332
TI  - A stable glucose biosensor prepared by co-immobilizing glucose oxidase into
      poly(p-chlorophenol) at a platinum electrode.
AB  - An amperometric glucose biosensor was successfully developed by electrochemical
      polymerization of p-chlorophenol (4-CP) at a Pt electrode in the presence of
      glucose oxidase. The amperometric response of this biosensor to hydrogen
      peroxide, formed as the product of enzymatic reaction, was measured at a
      potential of 0.6 V (vs. SCE) in phosphate buffer solution. The performances of
      sensors, prepared at different monomer concentrations and polymerization
      potentials, were investigated in detail. The biosensor prepared under optimal
      conditions had a linear response to glucose ranging from 2.5 x 10(-4) to 1.5 x
      10(-2) mol L(-1) with a correlation coefficient of 0.997 and a response time of
      less than 2 s. Substrate selectivity of the polymer-based enzyme electrode was
      tested for coexisting interferents such as uric acid and ascorbic acid, and no
      discernible response was observed. After 90 days, the response of the biosensor
      remained almost unchanged, indicating very good stability.

PMID- 11336333
TI  - Advantages of the iridium permanent modifier in fast programs applied to trace
      element analysis of plant samples by electrothermal atomic absorption
      spectrometry.
AB  - The application of a fast program combined with the advantages of the iridium
      permanent modifier is proposed for trace element analysis of plant samples by
      electrothermal atomic absorption spectrometry (ETAAS). For two volatile elements
      (Cd, Pb) and two mid-refractory elements (Cr, Ni) it was demonstrated that
      coating of the platform or of the tube atomization area with Ir is an efficient
      means of improving the accuracy and precision of results. A detailed study of
      interference from individual main matrix components and from composite plant
      matrices has confirmed the usefulness of the whole approach. The validity of the
      method has been confirmed by analysis of eight reference plant materials.

PMID- 11336334
TI  - Lead determination in slurries of biological materials by ETAAS using a W-Rh
      permanent modifier.
AB  - A tungsten-rhodium coating on the integrated platform of a transversely heated
      graphite atomiser (THGA) was used as a permanent chemical modifier for the
      determination of lead in biological materials by slurry sampling in
      electrothermal atomic absorption spectrometry (ETAAS). Slurries were sonicated
      during 20 s before being delivered to the previously W-Rh treated platform. The
      number of particles of biological materials introduced into the atomiser for
      delivering 20 microL slurry aliquot ranged from 5,100 to 39,000. The permanent W
      Rh modifier remained stable during approximately 300 analytical measurements when
      20 microL of slurries containing up to 1.5% m/v were delivered into the atomiser.
      In addition, the permanent modifier increases the tube lifetime by approximately
      100% when compared to untreated integrated platforms. Also, there is less
      decrease of sensitivity during the atomiser lifetime when compared with the
      conventional modifiers, resulting in a decreased need of re-calibration during
      routine analysis and consequently increasing the sample throughput. The atomiser
      lifetime was limited to the THGA wall durability, because the W-Rh treated
      platform was intact after more than 650 analytical firings in a medium containing
      up to 1.5% m/v slurry of biological material. The detection limit based on
      integrated absorbance was 20 ng g(-1) Pb for 1.50% m/v slurries. Results from the
      determination of lead in slurries of biological materials using the W-Rh
      permanent modifier were in agreement with those obtained with digested solutions
      using Pd + Mg(NO3)2.

PMID- 11336335
TI  - Multiresidue determination of organophosphorus and organochlorine pesticides in
      human biological fluids by capillary gas chromatography.
AB  - Two multiresidue analytical methods for the simultaneous determination of
      organophosphorus and organochlorine pesticides in human urine and serum samples
      are described. The first approach is based on liquid-liquid microextraction with
      dichloromethane, and the second uses solid-phase extraction with C18. In both
      methods, the extracts are analyzed by capillary gas chromatography using nitrogen
      phosphorus detection (NPD) and electron-capture detection (ECD). Limits of
      detection of the overall procedure of analysis are at the low ng mL(-1) level.
      Stability experiments have been performed with spiked urine and serum samples
      stored at 4 degrees C for 1 month. Finally, the solid-phase extraction procedure
      was applied to real-world samples. Quantification was performed by NPD or ECD,
      and peak identity was confirmed by use of mass-selective detection (MSD).

PMID- 11336336
TI  - Speciation of butyltin compounds in marine sediments with headspace solid phase
      microextraction and gas chromatography mass spectrometry.
AB  - A method for the determination of organotin compounds (monobutyl = MBT, dibutyl =
      DBT, and tributyltin = TBT) in marine sediments by headspace Solid Phase
      Microextraction (SPME) has been developed. The analytical procedure involved 1)
      extraction of TBT, DBT and MBT from sediments with HCl and methanol mixture, 2)
      in situ derivatization with sodium tetraethylborate and 3) headspace SPME
      extraction using a fiber coated with poly(dimethylsiloxane). The derivatized
      organotin compounds were desorbed into the splitless injector and simultaneously
      analyzed by gas chromatography - mass spectrometry. The analytical method was
      optimized with respect to derivatization reaction and extraction conditions. The
      detection limits obtained for MBT, DBT and TBT ranged from 730 to 969 pg/g as Sn
      dry weight. Linear calibration curves were obtained for all analytes in the range
      of 30-1000 ng/L as Sn. Analysis of a standard reference sediment (CRM 462)
      demonstrates the suitability of this method for the determination of butyltin
      compounds in marine sediments. The application to the determination of TBT, DBT
      and MBT in a coastal marine sediment is shown.

PMID- 11336337
TI  - Potential of microbore HPLC within a multiresidue method for the trace analysis
      of plant-protective substances in water.
AB  - The performance of microbore HPLC as a "measurement channel" within a true
      multiclass/multiresidue method for monitoring plant protectants in raw and
      potable water is demonstrated. The method has a modular design and consists of a
      non-selective sampling and preparation line generating 250 microL of an "extract"
      from a 100-mL water sample; this extract can be introduced to up to four
      measurement channels, as required by the analytical task. The microbore HPLC
      channel can be used to quantify 34 plant protectants in the 0.1 microg L(-1)
      concentration range by use of diode-array detection at seven different
      wavelengths. A solvent change is necessary to link sample preparation to
      microbore HPLC; this uses 50 microL of the "extract" and is accomplished directly
      in an autosampler vial. Performance characteristics were evaluated for tap water
      spiked at 0.2 microg L(-1). Average recoveries were between 65 and 100% and
      method detection limits were 0.07 microg L(-1) or better. The ability to provide
      comparable and accurate results was proven by participation in an interlaboratory
      comparison trial. The procedure for preparing microbore columns from 750 microm
      i.d. PEEK tubing is described in detail to enable the reader to prepare his own
      columns. The reproducibility of this preparation procedure was proven by an
      analysis-of-variance test.

PMID- 11336338
TI  - Determination of gaseous toluene diisocyanate by use of solid-phase
      microextraction with on-fibre derivatisation.
AB  - An SPME method was developed for sampling gaseous 2,4-toluene diisocyanate (2,4
      TDI) involving derivatisation of the isocyanate by reacting with dibutylamine
      (DBA). The TDI-DBA derivative thus formed was determined by LC-MS-MS utilising
      atmospheric pressure chemical ionisation (APCI). As a first step, DBA was loaded
      onto a poly(dimethylsiloxane)/divinylbenzene (PDMS-DVB) fibre coating by direct
      vapour-phase extraction of a highly concentrated diethyl ether solution of DBA.
      The DBA-loaded fibre was then exposed to an artificially generated atmosphere of
      gaseous 2,4-TDI. The linearity of the method ranged from 52.8 to 3100 microg m(
      3) (6.8 to 400 ppbv) with a sampling time of 60 min. The proposed method has been
      applied to 2,4-TDI determination in an artificially generated dynamic standard
      atmosphere, yielding an approximate method detection limit (MDL) of 2 microg m(
      3) (0.25 ppbv). This concentration is one twentieth of the Occupational Safety
      and Health Administration (OSHA) 8-hour time-weighted average (TWA) exposure
      limit. The sampler with the PDMS-DVB-DBA coating was found to be stable and
      retains the required amount of DBA for at least 10 days, an important feature for
      sampling systems with potential in-situ applications.

PMID- 11336339
TI  - A new spectrophotometric method for the determination of total and ferric iron in
      rain water at the ppb level.
AB  - A new, simple, selective and sensitive spectrophotometric procedure for the on
      site quantification of iron at nano-gram levels in atmospheric precipitations,
      i.e. rain as sample source is described. It is based on the color reaction of
      Fe3+ with SCN- ions in the presence of a cationic surfactant, i.e.
      cetylpyridinium chloride (CPC), in strong HCl solution, and subsequent extraction
      of the complex with N-octylacetamide into toluene or chloroform. The apparent
      molar absorptivity of the complex is 2.60 x 10(5) L mol(-1) cm(-1) at lambdamax =
      480 nm at an enrichment factor (EF) of 10. The detection limit (causing higher
      absorbance than the sum of the blank absorbance (0.009) and 3 SD) is 5 ng mL(-1)
      Fe. Ions commonly associated with iron did not interfere in the present method.
      The effect of analytical variables, i.e. amount and type of the reagents,
      acidity, solvent, temperature, dilution, etc., in the determination of iron are
      discussed. The validity of the present method is checked with GF-AAS. The method
      has been applied to the determination of iron at the ppb level in rain water
      samples.

PMID- 11336340
TI  - Thermal lens studies of the reaction of iron (II) with 1,10-phenanthroline at the
      nanogram level.
AB  - The determination of iron(II) with 1,10-phenanthroline in aqueous solutions was
      carried out exemplarily by thermal lens spectrometry. The peculiarities of
      analytical reactions at the nanogram level of reactants can be studied using this
      method. Under the conditions of the competing reaction of ligand protonation, the
      overall stability constant for iron(II) chelate with 1,10-phenanthroline was
      determined at a level of n x 10(-7) mol L(-1), logbeta3 = 21.3+/-0.1. The rates
      of formation and dissociation of iron(II) tris-(1,10-phenanthrolinate) at a level
      of n x 10(-8) mol L(-1) were found to be (2.05+/-0.05) x 10(-2) min(-1) and
      (3.0+/-0.1) x 10(-3) min(-1), respectively. The conditions for the determination
      of iron(II) with 1,10-phenanthroline by thermal lensing were reconsidered, and
      ascorbic acid was shown to be the best reducing agent, which provided minimum and
      reproducible sample pretreatment. Changes in the conditions at the nanogram level
      improved both the selectivity and sensitivity of determination. The optimum
      measurement conditions for thermal lensing were determined not only by the
      absorption of the analyte and reagents, but also by the background absorption of
      the solvent. The limits of detection and quantification of iron(II) at 488.0 nm
      (excitation beam power 140 mW) are 1 x 10(-9) and 6 x 10(-9) mol L(-1),
      respectively; the reproducibility RSD for the range n x 10(-8)-n x 10(-6) mol L(
      1) is 2-5%.

PMID- 11336341
TI  - Extraction of iridium (IV) from hydrochloric acid media with crown ether in
      chloroform, and its determination by ICP-AES.
AB  - A new method for the quantitative extraction and determination of trace amounts
      of iridium from hydrochloric acid media has been established based on the
      formation of an ion-association complex of iridium hexachloro anion IrCl6(2-)
      with dicyclohexyl-18-crown-6 (DC18C6) oxonium cation in chloroform, then
      determination by inductively coupled plasma atomic emission spectrometry (ICP
      AES). The effect of various factors (solvent, acid concentration, crown ether,
      reagent concentration, shaking time, composition of the extracted species,
      foreign ions, etc.) on the extraction and back-extraction of iridium has been
      investigated. The procedure was used to determine traces of iridium in palladium
      chloride and rhodium chloride.

PMID- 11336342
TI  - Applicability of micellar electrokinetic chromatography to the analysis of
      estrogens in water.
AB  - Estrone, beta-estradiol and ethynylestradiol spiked in water were extracted using
      solid-phase extraction (SPE) and then directly determined by micellar
      electrokinetic chromatography (MEKC) with online concentration (sweeping). A 350
      mL original sample volume (10 nM each) was concentrated to 1 mL using SPE, and
      ca. 240 nL of this solution was injected onto an MEKC capillary column. After
      sweeping, the estrogen related compounds were detected using a commercial
      absorbance detection system with an LOD of 0.16-0.30 nM in the original sample.

PMID- 11336343
TI  - Recognition by macrophages and liver cells of opsonized phospholipid vesicles and
      phospholipid headgroups.
AB  - The interaction of liposomes with blood proteins is believed to play a critical
      role in the clearance pharmacokinetics and tissue distribution of intravenously
      injected liposomes. In this article we have focused our discussion on the
      interaction of liposomes with key blood proteins, which include immunoglobulins,
      complement proteins, apolipoproteins, fetuin, von Willebrand factor, and
      thrombospondin, and their role in liposome recognition by professional phagocytes
      and nonmacrophage hepatic cells. Alternatively, macrophages as well as
      hepatocytes and liver endothelial cells may phagocytose/endocytose liposomes via
      direct recognition of phospholipid headgroups. A number of plasma membrane
      receptors such as lectin receptors, CD14, various classes of scavenger receptors
      (e.g., classes A, B, and D), Fc-gammaRI and FcgammaRII-B2 may participate in
      phospholipid recognition. These concepts are also discussed.

PMID- 11336344
TI  - Correlation of the capacity factor in vesicular electrokinetic chromatography
      with the octanol:water partition coefficient for charged and neutral analytes.
AB  - PURPOSE: The aim of this study was to develop a method based upon electrokinetic
      chromatography (EKC) using oppositely charged surfactant vesicles as a buffer
      modifier to estimate hydrophobicity (log P) for a range of neutral and charged
      compounds. METHODS: Vesicles were formed from cetyltrimethylammonium bromide
      (CTAB) and sodium n-octyl sulfate (SOS). The size and polydispersity of the
      vesicles were characterized by electron microscopy, dynamic light scattering, and
      pulsed-field gradient NMR (PFG-NMR). PFG-NMR was also used to determine if ion
      pairing between cationic analytes and free SOS monomer occurred. The CTAB/SOS
      vesicles were used as a buffer modifier in capillary electrophoresis (CE). The
      capacity factor (log k') was calculated by determining the mobility of the
      analytes both in the presence and absence of vesicles. Log k' was determined for
      29 neutral and charged analytes. RESULTS; There was a linear relationship between
      the log of capacity factor (log k') and octanol/water partition coefficient (log
      P) for both neutral and basic species at pH 6.0, 7.3, and 10.2. This indicated
      that interaction between the cation and vesicle was dominated by hydrophobic
      forces. At pH 4.3, the log k' values for the least hydrophobic basic analytes
      were higher than expected, indicating that electrostatic attraction as well as
      hydrophobic forces contributed to the overall interaction between the cation and
      vesicle. Anionic compounds could not be evaluated using this system. CONCLUSION:
      Vesicular electrokinetic chromatography (VEKC) using surfactant vesicles as
      buffer modifiers is a promising method for the estimation of hydrophobicity.

PMID- 11336345
TI  - The application of near infrared spectroscopy and dynamic vapor sorption to
      quantify low amorphous contents of crystalline lactose.
AB  - PURPOSE: To explore the use of a combined near infrared spectroscopy and
      gravimetric sorption apparatus in providing an accurate quantification of
      amorphous contents of predominantly crystalline lactose. METHODS: Key wavelengths
      on the near infrared spectra of amorphous and crystalline lactose were used to
      construct a calibration plot of spectral fit to amorphous content. The extent of
      water sorption and desorption at 75% relative humidity (RH) was used to quantify
      the amount of amorphous material in the sample. RESULTS: Near infrared
      spectroscopy was used to quantify the amorphous contents of a set of 10 partially
      amorphous lactose samples using a calibration equation generated from an
      independent set of 17 samples. The results were found to be accurate to within 1%
      w/w amorphous content. Dynamic vapor sorption quantification relates the mass of
      water sorbed and subsequently desorbed during the crystallization process with
      the amount of amorphous material originally contained within the sample. It was
      possible to quantitatively detect as little as 1 mg of amorphous content in the
      sample. The percent amorphous content determination will thus be sample mass
      dependent, however, assuming a sample mass of 150 mg, the best detection would be
      ca. 0.7%. CONCLUSIONS: It has been found that both techniques may be used to
      quantify small quantities of amorphous material. The combination of the two
      techniques lends itself to added verification of results and thus increased
      reliability.

PMID- 11336346
TI  - In vitro protein release and degradation of poly-dl-lactide-poly(ethylene glycol)
      microspheres with entrapped human serum albumin: quantitative evaluation of the
      factors involved in protein release phases.
AB  - PURPOSE: To quantitatively evaluate the correlations between the amount of
      initial burst release and the surface-associated protein, and between the onset
      time for the second burst release and the matrix polymer degradation. METHODS:
      Human serum albumin (HSA) was microencapsulated in polylactide (PLA) and poly-dl
      lactide-poly(ethylene glycol) (PELA) with PEG contents of 5, 10, 20, and 30%,
      respectively, using the solvent extraction procedure based on formation of double
      emulsion w/o/w. Microspheres with similar particle size (1.7-2.0 microm), similar
      protein entrapment (2.1-2.8%) but different surface-associated proteins (9.3
      53.6%) were used to evaluate the in vitro matrix degradation and protein release
      profiles. Degradation was characterized by studying the intrinsic viscosity
      decrease, medium pH change, and weight loss of the microspheres. RESULTS: The
      matrix degradation and protein release profiles were highly dependent on the
      polymer composition of the microspheres. Faster decreases in the intrinsic
      viscosity of recovered matrix polymer, the microspheres weight, and the pH of
      degradation medium, and earlier onsets for the break in intrinsic viscosity
      reduction and the mass loss were detected for PELA microspheres with higher PEG
      content. The hydration and swelling of microspheres matrix contributed greatly to
      the degradation of matrix polymer. The HSA release showed triphasic profile and
      involved two mechanisms for all the microsphere samples. Smaller amount of
      initial burst release, larger gradual release rate, and earlier onset for the
      second burst release were observed for HSA from matrix polymer with higher PEG
      content. The extent of the initial burst release was quantitatively related with
      the surface-associated protein. The second burst release of HSA was observed to
      occur within 1 week after the onset for mass loss, which was also the break in
      the intrinsic viscosity reduction rate. CONCLUSION: Protein release profiles
      could be rationalized by optimizing the matrix polymer degradation and
      microsphere characteristics.

PMID- 11336347
TI  - Fourier transform infrared (FTIR) analysis of volatile compounds in expired gas
      for the monitoring of poisonings 1. Ethanol.

PMID- 11336348
TI  - Characterization of the amino acid transport of new immortalized choroid plexus
      epithelial cell lines: a novel in vitro system for investigating transport
      functions at the blood-cerebrospinal fluid barrier.
AB  - PURPOSE: To establish and characterize a choroid plexus epithelial cell line (TR
      CSFB) from a new type of transgenic rat harboring the temperature-sensitive
      simian virus 40 (ts SV 40) large T-antigen gene (Tg rat). METHODS: Choroid plexus
      epithelial cells were isolated from the Tg rat and cultured on a collagen-coated
      dish at 37 degrees C during the first period of 3 days. Cells were subsequently
      cultured at 33 degrees C to activate large T-antigen. At the third passage, cells
      were cloned by colony formation and isolated from other cells using a penicillin
      cup. RESULTS: Five immortalized cell lines of choroid plexus epithelial cells (TR
      CSFB 1 approximately 5) were obtained from two Tg rats. These cell lines had a
      polygonal cell morphology, expressed the typical choroid plexus epithelial cell
      marker, transthyretin, and possessed Na+, K+-ATPase on their apical side. TR
      CSFBs cells expressed a large T-antigen and grew well at 33 degrees C with a
      doubling-time of 35 approximately 40 hr. [3H]-L-Proline uptake by TR-CSFB cells
      took place in an Na+-dependent, ouabain-sensitive, energy-dependent, and
      concentration-dependent manner. It was also inhibited by alpha
      methylaminoisobutylic acid, suggesting that system A for amino acids operates in
      TR-CSFB cells. When [3H]-L-proline uptake was measured using the Transwell
      device, the L-proline uptake rate following application to the apical side was
      five-fold greater than that following application to the basal side. In addition,
      both Na+-dependent and Na+-independent L-glutamic acid (L-Glu) uptake processes
      were present in TR-CSFB cells. CONCLUSIONS: Immortalized choroid plexus
      epithelial cell lines were successfully established from Tg rats and have the
      properties of choroid plexus epithelial cells, and amino acid transport activity
      was observed in vivo.

PMID- 11336349
TI  - Extravasation of poly(amidoamine) (PAMAM) dendrimers across microvascular network
      endothelium.
AB  - PURPOSE: To study the influence of a controlled incremental increase in size and
      molecular weight of a series of poly(amidoamine) (PAMAM) dendrimers on their
      extravasation across the microvascular network endothelium. METHODS: A series of
      PAMAM dendrimers (generations 0-4) were fluorescently labeled using fluorescein
      isothiocyanate (FITC). Purification and fractionation of the fluorescently
      labeled polymers were done using size exclusion chromatography. The hamster
      cremaster muscle preparation was used as an in vivo model to study the
      extravasation process of the fluorescently labeled polymers. The extravasation
      process was visualized and recorded using intravital microscopy techniques.
      Analysis of the recorded experiments was done using Metamorph Imaging System.
      Extravasation of the fluorescently labeled polymers is reported in terms of their
      extravasation time (tau), i.e., the time needed for the fluorescence intensity in
      the interstitial tissue to reach 90% of the fluorescence intensity in the
      neighboring microvessels. RESULTS: Extravasation time (tau) describes the rate of
      microvascular extravasation of polymeric drug carriers across the microvascular
      endothelium into the interstitial tissue. Extravasation time (tau) of the studied
      PAMAM dendrimers showed size and molecular weight dependence. An increase in size
      and/or molecular weight of PAMAM dendrimers resulted in a corresponding
      exponential increase in the extravasation time (tau). CONCLUSIONS: Extravasation
      of PAMAM dendrimers across the microvascular endothelium showed size and
      molecular weight dependence. Results suggest that in addition to size and
      molecular weight, other physicochemical properties of polymeric drug carriers
      such as molecular geometry and charge may influence their microvascular
      extravasation. Systematic studies of the influence of the physico-chemical
      properties of polymeric drug carriers on their microvascular extravasation will
      aid in the design of novel macromolecular drug carriers with controlled
      extravasation profiles.

PMID- 11336350
TI  - Differences in the intracellular distribution of acid-sensitive doxorubicin
      protein conjugates in comparison to free and liposomal formulated doxorubicin as
      shown by confocal microscopy.
AB  - PURPOSE: To investigate differences in the cellular uptake and intracellular
      distribution of protein-bound doxorubicin in comparison to free doxorubicin and a
      liposomal formulation (CAELYX) METHODS: LXFL 529 lung carcinoma cells were
      incubated with an acid-sensitive transferrin and albumin conjugate of
      doxorubicin, a stable albumin doxorubicin conjugate, and free and liposomal
      doxorubicin for up to 24 h. The uptake of doxorubicin was detected with confocal
      laser scanning microscopy (CLSM). To investigate the intracellular localization
      of the anticancer drug, lysosomes, Golgi apparatus, and mitochondria were also
      stained by various organelle-specific fluorescent markers. In vitro efficacy of
      the doxorubicin derivatives was examined with the BrdU incorporation assay.
      RESULTS: The acid-sensitive albumin and transferrin doxorubicin conjugates showed
      enhanced cytotoxicity in comparison to liposomal doxorubicin, whereas the stable
      albumin-doxorubicin conjugate showed only marginal activity. Of all compounds
      tested, doxorubicin showed the highest cytotoxicity. CLSM studies with specific
      markers for lysosomes, mitochondria, and the Golgi apparatus demonstrated that
      protein-bound doxorubicin or liberated doxorubicin was accumulated in the
      mitochondria and Golgi compartments, but not in the lysosomes after 24 h. Free
      doxorubicin showed a time-dependent intracellular shift from the nucleus to the
      mitochondria and Golgi apparatus. Fluorescence resulting from incubation with
      CAELYX was primarily detected in the nucleus. CONCLUSIONS: Our results indicate
      that other organelles in addition to the cell nucleus are important sites of
      accumulation and interaction for protein-bound doxorubicin or intracellularly
      released doxorubicin as well as for free doxorubicin.

PMID- 11336351
TI  - A human lymphocyte based ex vivo assay to study the effect of drugs on P
      glycoprotein (P-gp) function.
AB  - PURPOSE: The effect of drugs on P-glycoprotein (P-gp) is normally studied in
      transfected or overexpressing cell lines derived from tumor cells or animal
      tissue. We wanted to develop an assay using normal healthy human tissue to study
      and characterize the drug-transporter interaction. METHODS: Lymphocytes were
      isolated from healthy human blood. The effect of inhibitors of P-gp
      (cyclosporine, tacrolimus, verapamil, quinidine, vinblastine) and of other
      transporters (indomethacin, probenecid, sulfinpyrazone) on intracellular
      accumulation of rhodamine 123 was evaluated by flow cytometry. RESULTS: The
      efflux of rhodamine 123 was inhibited by P-gp inhibitors in a saturable,
      concentration-dependent manner. The potency of inhibition of P-gp was
      cyclosporine > tacrolimus > quinidine > verapamil > vinblastine. Vinblastine
      inhibited P-gp at lower concentrations, whereas at high concentrations, there was
      an activation of rhodamine 123 efflux from lymphocytes. The multidrug resistance
      associated protein (MRP) inhibitors, sulfinpyrazone and probenecid, did not have
      any significant effect on intracellular accumulation of rhodamine 123, but
      indomethacin caused a concentration-dependent increase in retention of rhodamine
      123, indicating the involvement of other uncharacterized transporters.
      CONCLUSIONS: Lymphocytes can serve as a model tissue for studying modulation of P
      gp activity by drugs. Both inhibitors and inducers of P-gp activity can be
      evaluated.

PMID- 11336352
TI  - Interaction of bile salt and phospholipids with bovine submaxillary mucin.
AB  - PURPOSE: The purpose of this study was to determine the distribution and
      diffusion of sodium taurocholate-phospholipid micelles with mucin in order to
      provide the foundation for understanding the transport of ingested fat and poorly
      water-soluble drugs through the intestinal mucous layer. METHODS: Sodium
      taurocholate (NaTC) was dispersed with egg phosphatidylcholines (PC) to yield
      mixed micelles of a specific size and concentration. A preliminary study was
      conducted to determine the time required for equilibration of PC/TC micellar
      solutions with mucin. PC/TC micellar solutions were dialyzed against fixed and
      variable concentrations of bovine submaxillary mucin after which the
      concentration of PC and NaTC was measured by an assay for total phosphorus and by
      HPLC, respectively. In addition, a quantitative assay of TC and PC by NMR was
      developed and used to estimate the mobile fraction of lipids in the samples.
      Finally, pulsed-field gradient spin echo NMR self-diffusion measurements were
      made of the water, TC, and PC in the samples obtained from dialysis. RESULTS:
      TC/PC micellar solutions achieved equilibrium with mucin in 7 days. Mucin did not
      affect the equilibrium concentration of PC or TC, except at high concentrations
      of mucin (5%), and then the effect was small. NMR quantitation was valid for PC
      and TC systems containing small micelles, but deviated significantly with systems
      containing large micelles. Mucin decreased the diffusivity of water and the
      phospholipids, but the effect was relatively small. Mucin dramatically affected
      the mobility of TC, which prevented a straightforward interpretation of the
      calculated diffusion coefficients. CONCLUSIONS: Mucin has a minor effect on the
      equilibrium distribution of phospholipids and bile salts. However, lipids are
      readily accommodated by mucus, which can significantly increase the permeability
      of the mucous layer, particularly for poorly water-soluble drugs.

PMID- 11336353
TI  - Optimization of lipid composition in cationic emulsion as in vitro and in vivo
      transfection agents.
AB  - PURPOSE: To enhance in vitro and in vivo transfection activity by optimizing
      lipid composition of cationic lipid emulsions. METHODS: Various emulsion
      formulations having different cationic lipids as emulsifiers, and additional
      helper lipids as co-emulsifiers, were prepared. The stability of the emulsion and
      its complex with DNA was investigated by measuring the particle size change in
      phosphate buffer saline (PBS) over a period of 20 days. The activity of the
      emulsions in transfecting pCMV-beta into COS-1 cells in the presence or absence
      of 80% serum was evaluated. We also evaluated in vivo transfection activity using
      intravenously administered pCMV-Luc+ as a reporter gene. RESULTS: Among the
      cationic emulsifiers, 1,2-dioleoyl-sn-glycero-3-trimethylammonium-propane (DOTAP)
      formed the most stable and efficient emulsion gene carrier. Addition of 1,2
      dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) increased in vitro transfection
      activity, but slightly compromised the stability of the emulsion. The loss was
      compensated for by including small amounts of Tween 80 in the emulsion. The in
      vitro and in vivo transfection activities were also increased by adding Tween 80.
      Even though in vitro transfection activity of liposomes was high in the absence
      of serum, the transfection activity of emulsions was far greater than that of
      liposomes in the presence of serum and for in vivo applications. CONCLUSIONS: By
      including DOPE as an endosomolytic agent and Tween 80 as a stabilization agent,
      the cationic emulsion becomes a more potent gene carrier for in vitro and in vivo
      applications, especially in the presence of serum.

PMID- 11336354
TI  - Topical gene transfer into rat skin using electroporation.
AB  - PURPOSE: To investigate whether electroporation can be used for topical gene
      delivery and for DNA expression in rat keratinocytes. METHODS: The localization
      of a fluorescent-labelled plasmid and the expression of a reporter gene (pEGFP
      N1) coding for Green Fluorescent Protein (GFP) in stripped skin were assessed by
      Confocal Laser Scanning Microscopy (CLSM). RESULTS: The plasmid penetrated into
      the epidermis within minutes after electroporation and entered the keratinocyte
      cytoplasm within hours. A localized expression of GFP was observed for at least 7
      days in the epidermis. Skin viability was not compromised by electroporation.
      CONCLUSIONS: Electroporation enhances the delivery, and hence the expression, of
      topically applied plasmid DNA on the skin. It could be a promising alternative
      method to administer DNA, particularly for DNA vaccines, in the skin in vivo.

PMID- 11336355
TI  - Pharmacokinetics of plasmid DNA in the rat.
AB  - PURPOSE: The pharmacokinetics of plasmid DNA after IV bolus administration in the
      rat by following supercoiled (SC), open circular (OC), and linear (L) pDNA forms
      of the plasmid. METHODS: SC, OC, and L pDNA were injected at 2,500, 500, 333, and
      250 microg doses. The concentrations in the bloodstream of OC and L pDNA were
      monitored. RESULTS: SC pDNA was detectable in the bloodstream only after a 2,500
      microg dose, and had a clearance of 390(+/-50) ml/min and Vd of 81(+/-8) ml. The
      pharmacokinetics of OC pDNA exhibited non-linear characteristics with clearance
      ranging from 8.3(+/-0.8) to 1.3(+/-0.2) ml/min and a Vd of 39(+/-19) ml. L pDNA
      was cleared at 7.6(+/-2.3) ml/min and had a Vd of 37(+/-17) ml. AUC analysis
      revealed that 60(+/-10) % of the SC was converted to the OC form, and nearly
      complete conversion of the OC pDNA to L pDNA. Clearance of SC pDNA was decreased
      after liposome complexation to 87(+/-30) ml/min. However the clearance of OC and
      L pDNA was increased relative to naked pDNA at an equivalent dose to 37(+/-9)
      ml/min and 95(+/-37) ml/min respectively. CONCLUSIONS: SC pDNA is rapidly
      metabolized and cleared from the circulation. OC pDNA displays non-linear
      pharmacokinetics. Linear pDNA exhibits first order kinetics. Liposome
      complexation protects the SC topoform, but the complexes are more rapidly cleared
      than the naked pDNA.

PMID- 11336356
TI  - Design and power of a population pharmacokinetic study.
AB  - PURPOSE: This paper investigated the influence of critical design factors on the
      power of a population pharmacokinetic (PK) study for identifying subpopulations
      that have different drug clearance than the typical population. METHODS: A study
      simulation approach was used for the power estimation. The design factors
      included the number of subjects, sampling scheme, and compliance. RESULTS: The
      false positive rates of incorrectly identifying a subpopulation were estimated
      for several scenarios. The false positive rates of the population PK study was
      relatively low, except when the numbers of subjects with full profiles and the
      subjects with troughs were distributed between populations in an unbalanced
      manner. The total number of subjects did not seem to have as much influence on
      study power as the number of subjects in the subpopulation, as long as the total
      number of subjects was significantly larger than the subpopulation. The
      variability of sampling time played an important role in both the statistical
      power and the accuracy of the estimated difference in clearance. Taking three
      samples provided greater power and better accuracy than taking two samples per
      subject. Taking only trough samples provided little power and poor estimation of
      clearance difference. Adding subjects with full profiles to a study with only
      trough samples taken in other subjects did not satisfactorily improve the
      clearance estimation. It was critical to account for dosing record in the
      population PK analysis to achieve appropriate power and accuracy. If the
      variability in dosing time was accounted for in the analysis, it improved the
      accuracy of the estimated difference in clearance. Missing dose administrations
      reduced the study power and resulted in deviation of estimated clearance
      difference. CONCLUSIONS: The power of a study should be determined prospectively
      to ensure appropriate study design for specific study objectives.

PMID- 11336357
TI  - Optimal design of a population pharmacodynamic experiment for ivabradine.
AB  - PURPOSE: To design a parsimonious population pharmacodynamic experiment that has
      the same or greater efficiency than that provided by two phase I studies.
      METHODS: The design was based on optimization of the population Fisher
      information matrix. Options for optimization were (1) determination of the
      optimal sampling times for each group ("group" represents a group of subjects
      that have identical design characteristics), (2) determination of the optimal
      doses for each group, and (3) determination of the optimal group structure.
      RESULTS: (1) Optimizing the sampling times, while retaining only four unique
      times per group, provided a more parsimonious experiment with the same efficiency
      as the original "study" that involved on average 10 samples per subject.
      Splitting sampling times between the first dose and a steady-state dose gave the
      most informative design. (2) The optimal dose was the same in all groups and was
      the upper bound of the dose range. (3) The optimal population design consisted of
      only one group with four unique sampling times that are the same for all
      subjects. CONCLUSION: A population pharmacodynamic trial design is presented that
      is more parsimonious than the original study and would be appropriate for
      inclusion in a premarketing clinical study.

PMID- 11336358
TI  - Establishment of bone marrow-derived endothelial cell lines from ts-SV40 T
      antigen gene transgenic rats.
AB  - PURPOSE: Postneonatal neovascularization is thought to result exclusively from
      the proliferation, migration, and remodeling of fully differentiated endothelial
      cells (ECs). Recently, it has been reported that bone marrow contains cells which
      can differentiate into ECs and contribute to neoangiogenesis in adult species. In
      this study, we tried to establish conditionally immortalized endothelial cell
      lines (TR-BME) derived from rat bone marrow. METHODS: Mononuclear cells were
      isolated and differentiated into ECs at 37 degrees C from the bone marrow of a
      transgenic rat harboring temperature-sensitive SV40 large T-antigen (ts T-Ag)
      gene. Then, the cells were transferred and incubated at 33 degrees C, a
      permissive temperature for ts T-Ag. Expression of vascular endothelial growth
      factor (VEGF) receptor (VEGFR)-1, 2, Tie-1, 2 and von Willebrand factor (VWF)
      were assayed by reverse transcriptase-mediated polymerase chain reaction (RT
      PCR). RESULTS: We have established three cell lines incorporating 1,1'
      dioctadecyl-3,3,3',3-tetramethylindo-carbocyanine perchlorate (DiI-Ac-LDL) with a
      spindle shape. One of these, clone 2, strongly expressed VEGFR-2, and weakly
      expressed VEGFR-1 and VWF. In contrast, clone 8 showed strong expression of Tie
      1, 2, and VWF, and weak expression of VEGFR-1,2. All markers were expressed
      strongly in clone 3. CONCLUSIONS: These data confirm that the above three TR-BME
      cells are novel ECs derived from bone marrow progenitors.

PMID- 11336359
TI  - Effect of initial buffer composition on pH changes during far-from-equilibrium
      freezing of sodium phosphate buffer solutions.
AB  - PURPOSE: This study aims to assess the pH changes induced by salt precipitation
      during far-from-equilibrium freezing of sodium phosphate buffers as a function of
      buffer composition, under experimental conditions relevant to pharmaceutical
      applications-sample volumes larger than a few microliters, experiencing large
      degrees of undercooling and supersaturation. METHODS: Buffer solutions were
      prepared by dissolving the monosodium and disodium phosphate salts in the
      appropriate ratios to obtain initial buffer concentrations in the range of 8-100
      mM and pH values between 5.7 and 7.4 at 25 degrees C. Temperature and pH were
      monitored in situ during cooling to -10 degrees C (at a rate of 0.3 to 0.5
      degrees C/min) and for 10-20 min after the sample reached the final temperature.
      Salt crystallization was confirmed by ion analysis and x-ray powder diffraction.
      RESULTS: Precipitation of Na2HPO4, 12H2O caused abrupt pH decreases after the
      onset of ice crystallization, at temperatures between -0.5 and -4.0 degrees C.
      Decreasing the initial buffer concentration and/or initial pH resulted in higher
      final pH values at -10 degrees C, farther removed from the equilibrium value of
      3.6. At an initial pH of 7.4, the 50 and 100 mM buffer solutions reached a pH of
      4.2 +/- 0.1 at -10 degrees C, whereas the 8 mM solutions reached a pH of 5.2 +/-
      0.2. Solutions having an initial pH of 5.7 and initial buffer concentrations of 8
      and 100 mM experienced less pH shifts upon freezing to -10 degrees C, with final
      pH values of 5.1 +/- 0.1 and 4.7 +/- 0.1, respectively. CONCLUSIONS:
      Precipitation-induced pH shifts are dependent on the concentrations (activities)
      of precipitating ions, and are determined by both initial pH and salt
      concentration. The ion activity product is a meaningful parameter when describing
      salt precipitation in solutions prepared by mixing salts containing precipitating
      and nonprecipitating ions.

PMID- 11336360
TI  - Detection of low levels of the amorphous phase in crystalline pharmaceutical
      materials by thermally stimulated current spectrometry.
AB  - PURPOSE: To demonstrate the applicability of thermally stimulated current (TSC)
      spectrometry for the detection of low levels of the amorphous phase in
      crystalline pharmaceutical materials. METHODS: A crystalline drug substance was
      melt quenched to produce an amorphous material. Blends of the crystalline and
      amorphous phases in different ratios (from 75:25 to 99:01) were prepared by
      serial dilution. TSC studies were performed by applying an electric field at a
      temperature above the glass transition temperature (Tg) to orient the dipoles,
      rapidly cooling to 0 degrees C, short circuiting for 1 min, and scanning at 7
      degrees C/min to measure the depolarization current. The temperature of the peak
      in the spectrum corresponds to the Tg of the amorphous phase. Modulated
      differential scanning calorimtery (DSC) studies were performed using three
      different test protocols (varying linear heating rate, modulation amplitude, and
      time period). Powder X-ray diffraction (XRD) studies were performed using a
      Siemens D500 diffractometer. RESULTS: The ability to detect the amorphous phase
      by powder XRD is beset with problems due to indirect inference, orientation
      effects, and instrument-related intensity variations. Even using a consistent
      sampling procedure and an internal standard, the XRD could quantify the amorphous
      phase at a level of 5%. In the conventional or modulated DSC, the amorphous phase
      manifests itself as a shift in the baseline. Using modulated DSC it was possible
      to detect the amorphous phase at a level of 5% when tested at a heating rate of 2
      degrees C/min and an amplitude of +/-1.0 degrees C with a period of 30 s. The
      moisture sorption method appears to have a similar detection capability. In TSC
      scans, the glass transition event due to molecular/segmental mobility in the
      amorphous phase was manifested as a peak/shoulder on the low-temperature side of
      the depolarization peak of the crystalline phase. The amorphous phase was
      unambiguously detected at 2% with a lower detection limit of approximately 1%.
      CONCLUSIONS: On the basis of the results of this preliminary investigation, TSC
      appears to be capable of detecting the amorphous phase at as low as approximately
      1% in crystalline pharmaceuticals, thus offering a much needed capability in
      discerning factors.

PMID- 11336361
TI  - The Seoul experience of splenic artery aneurysms.
AB  - BACKGROUND AND AIMS: Aneurysms of the splenic artery (SAA) are the most common
      type of aneurysms found in the splanchnic arterial bed (1) and are second in
      frequency only to aortic and iliac artery aneurysms among intra-abdominal
      aneurysms (2). Historically rupture occurs in 6-9.2% of asymptomatic cases and in
      pregnant women rupture occurs in 95% of afflicted women further emphasizing the
      importance of early diagnosis (3-5). Possible treatments are surgical resection
      or trans-catheteral arterial embolization. MATERIAL AND METHODS: The relationship
      of SAA to pregnancy, pancreatitis and the outcome after surgical resection or
      arterial embolization was studied. Fifteen patients were diagnosed with SAA
      between January, 1992 and December 1999. The patients were classified by their
      clinical characteristics, etiology, size, and location of the aneurysm,
      relationship to pregnancy in women, clinical outcome of ruptured aneurysms and
      treatment. RESULTS: Fifteen patients, male to female ratio of 1.1:1 (eight men,
      seven women), with splenic artery aneurysm were treated. Patients were mostly in
      their sixty's and the mean age was 49.07. Chronic pancreatitis and pseudocysts
      were found in four cases (26.7%). Acute pancreatitis, portal hypertension,
      splenomegaly, and bronchitis were comorbidities found each in one case (6.7%).
      Eight cases (53.3%) were without associated disease CONCLUSIONS: SAA has
      historically shown predominance in women, but in this study, men showed
      predominance and no relation to pregnancy could be found. In cases were the
      aneurysms ruptured and treatment was initiated, one of four patients died. One
      patient refused treatment and subsequently died. As most of the aneurysms measure
      over 2 cm at the time of detection, operative resection was recommended in all
      cases. In the high-risk patients, arterial embolization using coiling can be
      effective early in treatment, but arterial embolization in SAA secondary to
      pancreatitis was shown only to be palliative and needed to be complimented with
      surgical intervention. Arterial embolization is the method of choice in high-risk
      patients.

PMID- 11336362
TI  - Preliminary results with endoluminal femoropopliteal thrupass.
AB  - BACKGROUND AND AIMS: Results of endovascular procedures to the superficial
      femoral artery and popliteal artery are not as good as at the iliac level. The
      purpose of this study is to evaluate the long-term results of a new endoluminal
      stent-graft for the management of lesions of the femoropopliteal segment.
      MATERIAL AND METHODS: Fifteen patients underwent endoluminal treatment of
      femoropopliteal lesions with a PTFE covered stent-graft. Nine patients had
      critical leg ischaemia, two patients had acute leg ischaemia, two patients were
      claudicants, one patient had a ruptured popliteal artery aneurysm, and one had a
      large adjuvant therapeutic arteriovenous fistula. RESULTS: The procedure was
      successfully carried out in all patients. Thrombosis occurred in two stent-grafts
      4.5 months and 12.5 months after the procedure. One of them was successfully
      thrombolysed. During the two-year follow-up, a haemodynamically significant
      decrease in ankle/brachial index was observed in two patients. Ankle/brachial
      index was the same or higher than the immediately postoperative value in six
      patients. Primary patency rates at 1 month, 1 year and 2 year follow-up were
      100%, 93% and 84%, respectively. Assisted primary patency rates at the same
      intervals were 100%, 93% and 93%, respectively. No patient had limb loss during
      the follow-up period. CONCLUSIONS: Endoluminal femoropopliteal bypass using PTFE
      covered stent-graft can be successfully performed with good two-year results.

PMID- 11336363
TI  - Increased preoperative c-reactive protein level as a prognostic factor for
      postoperative amputation after femoropopliteal bypass surgery for CLI.
AB  - BACKGROUND AND AIMS: We evaluated the possible predictive role of C-reactive
      protein (CRP) on the immediate postoperative outcome after femoropopliteal bypass
      surgery for critical leg ischaemia (CLI). MATERIAL AND METHODS: 138 patients with
      CLI who underwent 143 femoropopliteal reconstructions. RESULTS: The immediate
      postoperative period secondary patency rate was 87%, leg salvage rate was 94%,
      and survival rate 97%. Nine patients (6.3%) had 30-day postoperative major
      amputation, three of them despite a patent bypass graft because of progression of
      foot infection. The preoperative serum concentration of CRP was the only
      predictor of postoperative major amputation (p = 0.004; for an increase of 10
      mg/l: OR, 1.188; CI 95%, 1.059-1.332). The median preoperative serum
      concentration of CRP among patients who did not have major amputation was 13.0
      mg/l (range, 1-185), whereas it was 47.5 mg/l (range, 5-168) among those who had
      amputation after bypass graft occlusion, and 115.0 mg/l (range, 34-222) among
      those who had amputation despite a patent bypass graft (p = 0.008). CONCLUSIONS:
      CRP may be a useful marker in risk stratification for postoperative amputation in
      patients undergoing femoropopliteal bypass surgery for CLI.

PMID- 11336364
TI  - Transfusion practice in primary unilateral total knee replacement arthroplasty;
      the need for guidelines.
AB  - BACKGROUND AND AIMS: There are no universally accepted guidelines for blood
      transfusion in primary, unilateral Total Knee Replacement Arthroplasty (TKA).
      Transfusion is associated with post-operative infection, fluid overload and
      prolonged duration of hospitalisation. Due to this morbidity and reports of
      "inappropriate" transfusion practice, an audit of the local practice was
      organised, with the aim of assessing compliance to existing evidence. METHODS: A
      1-year retrospective survey of blood transfusion practice was conducted for all
      consecutive elective, primary, unilateral TKA operations. RESULTS: 169 operations
      were performed; 96% for osteoarthritis; mean patient age was 69 years; 66% were
      females; 34% of the patients were transfused, 60% intra-operatively. There was no
      threshold of pre-operative Hb predictive of a transfusion and no significant
      difference in the pre-operative Hb between transfused and non-transfused groups.
      Only 26% of the cross-matched blood was eventually transfused. Intra-operative
      blood loss was negligible and only 10% of transfused patients had shown
      cardiovascular instability. The post-operative Hb drop was maximal at around day
      4. CONCLUSIONS: The lack of guidelines has led to inconsistent local transfusion
      practice, often with no scientific evidence to support it. In the absence of a
      randomised controlled trial addressing the issue, certain transfusion guidelines
      are suggested, based on existing indirect scientific evidence.

PMID- 11336365
TI  - Hip arthroscopy in osteoarthritis. A review of 68 patients.
AB  - BACKGROUND AND AIMS: A few studies have investigated therapeutic effect of hip
      arthroscopy in osteoarthritis, and therefore the use of hip arthroscopy in
      osteoarthritis has remained controversial. The aim of this study was to evaluate
      diagnostic and therapeutic aspects of hip arthroscopy in primary osteoarthritis.
      MATERIAL AND METHODS: During a time period from 1995 to 1999, a total of 68
      patients had an arthroscopic evaluation of primary hip osteoarthritis at the
      Paijat-Hame Central Hospital, Lahti, Finland. The mean (range) follow-up was 1.3
      (0.3 to 4) years. Arthroscopy was diagnostic in 38 (56%), while six (9%) patients
      received either long-lasting anaesthetic or prednisolone, and in 24 (35%)
      debridement was possible. Partial synovectomy was performed in two (3%). RESULTS:
      Three months after the arthroscopy, 49 (72%) patients reported that their hip
      pain had decreased. One year after the arthroscopy, 18 (26%) patients stated that
      their hip pain was less pronounced than before the arthroscopy. The severity of
      hip osteoarthritis in preoperative x-rays correlated significantly (p = 0.035)
      with the subjective result: the milder the osteoarthritis, the more often
      patients reported that their hip pain had decreased after arthroscopy. No
      association was observed between age, sex, modified Outerbridge grade of
      chondropathy, or whether a debridement was done or not and the symptomatic relief
      after the arthroscopy. CONCLUSIONS: Hip arthroscopy with or without debridement
      of loose cartilage may, at least temporarily, reduce the pain of mild or moderate
      osteoarthritis of the hip. Still, repeated arthroscopies had no therapeutic
      effect.

PMID- 11336366
TI  - Human genome project.

PMID- 11336367
TI  - Composite implant composed of hydroxyapatite and bone morphogenetic protein in
      the healing of a canine ulnar defect.
AB  - BACKGROUND AND AIMS: Hydroxyapatite (HA) has been considered as a carrier
      material for bone morphogenetic proteins (BMP). The aim of this study was to
      evaluate the capacity of a composite implant of HA and native bovine BMP to heal
      a 2 cm segmental defect in the canine ulna. MATERIALS AND METHODS: A composite
      HA+BMP implant was compared with plain HA implants and cortical autografts. The
      fixation was accomplished with an intramedullary Kirschner wire. The bone union
      was evaluated by X-rays taken at operation and after 3, 6, 9, 12, 16, 25, 35
      weeks and by histology and mechanical torsion tests. RESULTS: HA implants were
      not able to produce complete bone union even with BMP. There was some bridging
      between the implant and the bone in the defects treated with either plain HA or
      HA+BMP implant, the bridging being slightly more pronounced with HA+BMP. The
      autografts showed a significantly better capacity to heal the defect. The HA
      implant did not resorb markedly during the study. There was no significant
      difference in mechanical strength between the HA and HA+BMP groups. CONCLUSIONS:
      HA was not an adequate bone substitute material in this study model, and BMP was
      not able to enhance sufficiently the poor capacity of HA to heal canine ulnar
      defects.

PMID- 11336368
TI  - Pamidronate increases trabecular bone mineral density in immobilization
      osteopenia in male rats.
AB  - BACKGROUND AND AIMS: Osteopenia is a common consequence of immobilization. We
      investigated the effects of pamidronate on immobilized bone in male rats.
      MATERIAL AND METHODS: Eighty male Wistar rats (5 months old) were divided in five
      groups (control (C); pamidronate at 0.5 mg/kg per dose (Pam0.5); immobilization
      (N); pamidronate at 0.05 mg/kg per dose + immobilization (N + Pam0.05); and
      pamidronate at 0.5 mg/kg per dose + immobilization (N + Pam0.5). The rats were
      immobilized on their right side by sciatic neurectomy. Pamidronate was given
      subcutaneously three times a week for three weeks. Trabecular bone mineral
      density (TBMD) of the upper femur, ultimate failure load of the femoral
      diaphysis, ash weight of femur, calcium content of femoral ash, and ash weight
      corrected with bone volume (AWcc [g/cm3]) were determined. Histomorphometry of
      proximal tibiae was performed by a semiautomatic method. RESULTS: TBMD was higher
      on both sides in Pam0.5 and N + Pam0.5 groups than in C or N groups. Ultimate
      failure load was not altered significantly with treatment. AWcc of the
      immobilized femur was lower (p < 0.001) than in the contralateral limb in N, N +
      Pam0.05 and N + Pam0.5 groups. Both resorption and formation parameters were
      suppressed by pamidronate. CONCLUSION: Pamidronate treatment seemed to increase
      trabecular bone density, although it was not effective in maintaining the AWcc of
      the operated extremity. Pamidronate did not seem to affect the ultimate failure
      load of cortical bone.

PMID- 11336369
TI  - Peroneal tendon injuries. Report of thirty-eight operated cases.
AB  - BACKGROUND AND AIMS: Peroneal tendon injuries are probably frequently overlooked
      causes of lateral ankle pain after distorsion trauma. We report a series of 38
      patients with peroneal tendon injuries and outcome after operation. MATERIAL AND
      METHODS: The mean age of the patients was 30 years (range, 13 to 61). All
      patients were operated by the same orthopaedic surgeon (SO) and the final outcome
      was evaluated. RESULTS: Eighty-two per cent of the patients were competitive
      athletes. There were 11 partial and 3 total ruptures of the peroneus brevis
      tendon (PBT), 2 partial and 2 total ruptures of the peroneus longus tendon (PLT).
      Nine cases of subluxations or luxations were treated. There were also 5 cases of
      chronic peroneal tendinitis or tenosynovitis, 5 cases of peroneal tendon
      anomalies and 1 ganglion. The peroneal tendon lesion was associated to ankle
      instability in 19 cases (50%). In ninety percent of the cases the result of the
      operation was excellent or good. CONCLUSIONS: The lateral ligaments are usually
      damaged in ankle distorsion injuries, but peroneal tendon lesions are often
      overlooked and probably more common cause of persistent lateral ankle pain than
      previously thought. Ruptures and luxations of the peroneal tendons need operative
      treatment in most cases.

PMID- 11336370
TI  - Intra-articular ropivacaine injection does not alleviate pain after day-case knee
      arthroscopy performed under spinal anaesthesia.
AB  - BACKGROUND AND AIMS: To evaluate the effect of intra-articular ropivacaine
      injection on postoperative knee pain after day case arthroscopy. MATERIAL AND
      METHODS: We studied one hundred outpatients in a prospective, randomized, double
      blind fashion to examine the postoperative analgesic effect of intra-articular
      ropivacaine or saline injected into the knee joint after day-case knee
      arthroscopy performed under spinal anaesthesia. Patients were interviewed
      postoperatively with a standardized questionnaire. The postoperative pain was
      measured using a 100-mm visual analogue scale (VAS). RESULTS: There were no
      statistically significant differences in the VAS scores of knee pain eight hours
      or more after the operation between the intra-articular ropivacaine and saline
      groups, and there was no significant difference in the need for postoperative
      pain killer. CONCLUSIONS: This study failed to demonstrate a decrease in
      postoperative VAS scores at eight hours and later postoperatively when 20 ml of
      ropivacaine 0.5% were injected intra-articularly after day-case knee arthroscopy
      performed under spinal anaesthesia. Furthermore, there was no significant
      difference in the need for postoperative pain medication between the study
      groups.

PMID- 11336372
TI  - Adventitial cystic disease in the common femoral artery.
AB  - The rare condition of adventitial cystic disease with massive cysts in the common
      femoral artery was treated in a 49-year old man. The symptoms were calf and thigh
      claudication. Angiography showed occlusion of the common femoral artery and the
      deep femoral artery. The condition was obvious peroperatively, and after clearing
      the deep artery, a bypass (ePTFE) to the two femoral run off vessels was needed.
      After an uneventful postoperative period, it was observed at three months' follow
      up, that the patient had foot pulses.

PMID- 11336371
TI  - Treatment of prostate cancer--any news?

PMID- 11336373
TI  - Laparoscopic repair of rectal prolapse: surgical technique.
AB  - Technical features of laparoscopic rectopexy include complete rectal mobilization
      without division of the lateral stalks to avoid parasympathetic denervation and
      postoperative problems with defecation. Suture rectopexy is equally effective as
      posterior mesh rectopexy in preventing recurrences and eliminates the use of
      foreign material which is sometimes associated with intense fibrosis, sepsis and
      increased constipation. According to two randomised studies constipation seems to
      be less after resection rectopexy than suture or posterior mesh rectopexy alone
      perhaps by eliminating possible kinking at the rectosigmoid region by falling of
      the redundant sigmoid colon in the pouch of Douglas. Randomized studies are,
      however, needed to validate the need for colonic resection and to determine its
      optimal extent in patients who suffer from rectal prolapse, constipation and slow
      transit.

PMID- 11336374
TI  - Disability under Social Security for patients with ESRD: an evidence-based
      review.
AB  - PURPOSE: In the United States, all individuals with end-stage renal (ESRD)
      disease are automatically eligible for disability benefits under the Social
      Security Act. Recently, there have been questions about whether the diagnosis of
      ESRD alone is an appropriate criterion for determining disability under Social
      Security. METHODS: We conducted a systematic review of the published literature
      and de novo analysis of data from the United States Renal Data System (USRDS) in
      an attempt to identify the best predictors of inability to work that might be
      useful during the disability determination process. RESULTS: The published
      literature yielded little relevant evidence. The USRDS provided a prospectively
      collected set of data on 4,026 incident dialysis patients over their first year
      on dialysis, a time period particularly applicable to the key questions. However.
      data from over half of the patients were missing for the most important variables
      to this project, and only 42% of patients completed the one-year follow-up
      questionnaire. These limitations rendered de novo analyses unreliable. However,
      summary statistics did reveal a decreasing number of working individuals over
      time, from 41.9% before the initiation of dialysis. to 21.1% at initiation, and
      6.6% a year later.

PMID- 11336375
TI  - Spinal pain independence measure--a new scale for assessment of primary ADL
      dysfunction related to LBP.
AB  - PURPOSE/METHOD: SPIM Spinal Pain Independence Measure. a new disability scale
      designed for patients with chronic low back pain disability, has been developed
      and studied at the Spinal Department of Loewenstein Rehabilitation Hospital. The
      SPIM differs from other existing scales for evaluation of chronic back
      disability, in that it is designated particularly for patients with deficits in
      primary ADL and evaluates function by observation. RESULTS/CONCLUSIONS: This
      study shows the SPIM to be reliable: it supports the validity of the scale and
      points out a possible advantage of the SPIM over existing scales in sensitivity
      to functional change of patients with prominent disability. Further elaboration
      and examination of the SPIM is still needed.

PMID- 11336376
TI  - Usefulness of an individualized balance and gait intervention programme based on
      the problem-oriented assessment of mobility in nursing home residents.
AB  - PURPOSE: To examine the usefulness of an individualized balance and gait training
      proramme according to the specific problems identified from the problem-oriented
      assessment of mobility (POAM) in residents of a nursing home. METHOD: The
      clinical records of 74 NH residents (49 female, 25 male) who were consecutively
      referred to physical therapy for problems related to poor balance or gait or a
      recent fall in a 2 year period were reviewed retrospectively for the study.
      According to the medical charts, patients had received a four week (20 sessions)
      problem-oriented exercise programme that specifically targeted balance and gait
      deficits identified from the POAM and the retest had been done after four weeks
      of training. RESULTS: The mean initial and final balance scores were 8.47+/-3.80.
      and 10.77+ /-3.37. respectively, and the mean gait scores were 6.73+/-2.30
      initially and 7.71+/-1.95 finally. A Wilcoxon signed-rank comparison of the
      initial and final POAM indicated that significant improvement occurred in the
      balance scores (Z = 5.345, p < 0.0001) and the gait scale (Z = 3.589, p < 0.0001)
      in this group. Item analysis demonstrated the number of patients who improved or
      did not change on individual items. CONCLUSIONS: Both balance and gait were
      significantly improved after a four-week intervention programme based on the
      deficits identified by POAM. The POAM is a useful tool to guide the clinician to
      target specific balance and gait deficits for individual nursing home elders.

PMID- 11336377
TI  - Population-based survey of childhood disability in eastern Jeddah using the ten
      questions tool.
AB  - PURPOSE: To identify the prevalence of handicapping disabilities among children
      up to 15 years of age and their epidemiological pattern in the eastern part of
      Jeddah. METHODS: In a population-based cross-sectional household survey in the
      eastern Jeddah area, Saudi Arabia, a multistage sampling method was applied to
      screen children in 875 houses using the ten questions survey tool for
      identification of disabilities. Further information collected for detected
      disabilities included possible risk factors, cause of the disability as perceived
      by the family and services previously provided to the child. RESULTS: A total of
      137 cases of disability were detected giving a point prevalence rate of 36.7 per
      1,000 children. Twenty-nine children (21.2%) were discovered for the first time
      during the survey. The majority of cases were male (57.7%) and the mean age for
      all cases was 10 years (SD = 5.5) with no case detected under one year of age.
      Disabled children were in the fourth or fifth birth order among their brothers
      and sisters and 47 (34%) of them were recorded as a second or third disability in
      the same family. Number of disabilities in the same child varied widely: 59% of
      cases had a single disability. 22% had two conditions and 19% had three or more
      conditions. Speech. motor and mental disabilities ranked top of the disabilities
      detected by the ten-question tool. The commonest cause of these disabilities as
      perceived by the family was hereditary diseases followed by childhood illnesses.
      Significant risk factors associated to these conditions included larger number of
      children in the family, older age of either parent. histories of handicapping
      conditions in the original families of either of the parents and presence of
      handicapping condition in the mothers. Families reported lack of services
      provided to their disabled children in the community. CONCLUSIONS: The survey
      tool managed to document. successfully, a prevalence rate of childhood
      disabilities in the community with a general picture of their types and suspected
      causes which is quite comparable to that found in Saudi Arabia. It also reported
      a low service delivery for these disabilities and identified some risk factors
      related to their occurrence. It is recommended to apply this survey method with
      certain modifications to suit the local culture in Saudi Arabia. Improvement of
      the services rendered to handicapped children in Jeddah is also recommended.

PMID- 11336378
TI  - The effects of atrial fibrillation on functional recovery in post-stroke
      patients.
AB  - PURPOSE: This study evaluates the negative effects of atrial fibrillation (AF) on
      after stroke recovery and its relationship with age and other concomitant
      diseases. METHOD: One hundred and ninety-nine consecutive inpatients, after their
      first stroke, were enrolled and entered a rehabilitation program lasting 60 days.
      The mean interval since the stroke was 19 days. The disability, both at admission
      and at discharge, was assessed by Functional Independence Measure (FIM). Atrial
      fibrillation was diagnosed at admission on the basis of electrocardiographic
      recordings. Gender, age, blood pressure and blood sugar level were also taken
      into account. RESULTS: Stroke patients suffering from AF, when compared to those
      lacking AF, have higher disability at admission as well as at discharge and had a
      lesser gain in functional recovery. No statistical difference of the AF
      occurrence was found between male and female patients. The negative correlation
      between age and functional gain was found only in AF patients. There was also a
      significant association between AF and hypertension, but not between AF and
      diabetes. At the beginning and at the end of the study, the median FIM scores of
      all the patients with AF were quite similar irrespective of manifesting
      hypertension, diabetes or neither of these two. CONCLUSIONS: The presence of AF
      has a negative prognostic value on post stroke outcome, particularly in the
      elderly patients. The pattern of recovery of stroke subjects having AF is not
      influenced by concomitant diseases like hypertension or diabetes.

PMID- 11336379
TI  - A conceptual framework for the study of the quality of rehabilitation.
AB  - PURPOSE: To propose a framework for the assessment and ongoing, continuous
      improvement of the quality of rehabilitation care. METHOD: The generally
      clarified and accepted approaches to the study of the quality of care are
      examined in view of the inherent characteristics of medical rehabilitation, and
      the differences between it and other fields of medical practice. RESULT: Process
      and outcome of care are distinct but complementary, and their elements should, in
      rehabilitation. be used jointly and simultaneously as indicators of quality.
      CONCLUSION: Rehabilitation is of long duration and consists of various phases,
      each of them focusing on a different issue. It is proposed to monitor activities
      of rehabilitation professionals (process elements) and constitute the focus of
      care of a given phase, and simultaneously to monitor relevant outcome elements
      attributable to the activities of the given phase. Comparison of monitored
      elements (the observed care) to their standards (the expected care) would enable
      assessment of the quality and its continuous improvement.

PMID- 11336380
TI  - Commentary on: a conceptual proposal for the study of the quality of
      rehabilitation care.

PMID- 11336381
TI  - Commentary on the paper: 'A conceptual proposal for the study of the quality of
      rehabilitation care' by Dr Ruben Eldar.

PMID- 11336382
TI  - Commentary on 'A conceptual proposal for the study of the quality of
      rehabilitation care.'.

PMID- 11336383
TI  - Commentary on 'A conceptual proposal for the study of the quality of
      rehabilitation care'.

PMID- 11336384
TI  - Swelling properties of various polymers used in controlled release systems.
AB  - The effect of powder packing and porosity of specimens on the swelling properties
      of polymeric materials was studied, in various swelling liquids, such as
      distilled water and 0.1 N hydrochloric acid solution. Capsules, tablets and films
      of hydroxypropyl methylcellulose, poly(ethylene oxide) and sodium alginate were
      prepared, and their weight uptake after immersion into the above solutions was
      recorded as a function of time, in order to assess the swelling process.
      Measurements of some characteristics of the as-received powders were also
      performed in an attempt to classify the specimens prepared according to their
      porosity. Within the experimental conditions of this work, it was shown that the
      porosity of polymeric specimens is a dominant factor that controls their swelling
      behaviour. Increased porosity leads to fast initial rates of weight uptake and
      high extent of equilibrium swelling. On the other hand, dissolution and possible
      degradation of polymers susceptible to acid hydrolysis results in some variations
      from the above mentioned behaviour. With respect to the application in controlled
      release systems, the overall delivery rate from a polymeric specimen is expected
      to be a function of both swelling and disintegration characteristics of a
      specimen, and therefore, the weight uptake can be considered a measure of the
      release only in the case of polymers with low water solubility and increased
      stability to hydrolysis.

PMID- 11336385
TI  - Synthetic hydrogels as carriers in antisense therapy: preliminary evaluation of
      an oligodeoxynucleotide covalent conjugate with a copolymer of 1-vinyl-2
      pyrrolidinone and 2-hydroxyethyl methacrylate.
AB  - A major challenge of the antisense therapeutic strategies is the development of
      improved systems for the delivery of antisense oligodeoxynucleotides (AS ODNs) in
      order to enhance the cellular uptake, to assure a better efficiency in reaching
      the target tissue, and to provide sustained delivery over longer periods of time.
      Because the current methods for delivery (liposomes and cationic polymers)
      present some disadvantages, the attention was directed toward the use of neutral
      polymers as carriers for the AS ODNs. Based on our previous work on synthetic
      hydrogels for vitreous substitution, we developed a poly[1-vinyl-2-pyrrolidinone
      co-(2-hydroxyethyl methacrylate)] hydrogel as a potential carrier for AS ODNs. We
      have previously demonstrated that such hydrogels are not cytotoxic, and they may
      have growth-promoting effects on cultured fibroblasts. This copolymer also has
      the advantage of being injectable. In this study, a specific AS ODN was
      synthesized and then covalently bound to the copolymer via carbodiimide coupling
      method. The resulting conjugate was subjected to in vitro release experiments
      over 46 days in the presence of bovine vitreous humor. Compared with the control
      (no enzyme present), a significant amount of covalently bound ODN was released
      from the ODN-hydrogel conjugate, suggesting the possibility of using such systems
      for the sustained delivery of AS ODNs.

PMID- 11336386
TI  - Gellan film as an implant for insulin delivery.
AB  - Gellan gum is an anionic polysaccharide produced by the aerobic fermentation of
      Pseudomonas elodea in batch culture. Gellan undergoes calcium-induced cross
      linking to form a three-dimensional network, and this property makes it
      particularly attractive for the incorporation of biological moieties such as
      proteins. In this study, a procedure for the preparation of gellan films was
      developed and optimized, and the characteristics of these films were
      investigated. In addition, the effects of the concentration of each ingredient in
      gellan films and in vitro release behavior of fluorescein isothiocyanate dextran
      from these films was examined. This film device was implanted for insulin
      delivery in diabetic rats. The blood glucose levels of the diabetic rats
      implanted with insulin-loaded films were about half of those implanted with blank
      films, and this therapeutic effect of insulin could last for one week. Both in
      vitro and in vivo studies indicated that the gellan film could be an ideal
      candidate in the development of protein delivery systems.

PMID- 11336387
TI  - A comparative evaluation of coefficient of friction and mechanical properties of
      commercially available Foley catheters.
AB  - Three commercially available urinary catheters were evaluated for their
      coefficient of friction and mechanical properties, which are two important
      parameters as far as the intended use is considered. The apparent coefficient of
      friction was measured from the slope of the force versus normal load graph using
      an in-house fabricated setup. The mechanical properties like ultimate tensile
      strength, elongation at break and modulus were evaluated before and after aging
      in synthetic urine. The swelling behavior of the catheter samples was studied in
      toluene and found to correlate well with the mechanical properties.

PMID- 11336388
TI  - The effect of woven, chopped and longitudinal glass fibers reinforcement on the
      transverse strength of a repair resin.
AB  - Fracture resistance of prosthesis is an important clinical concern. This property
      is directly related to transverse strength. Strengthening of prostheses may
      result from reinforcement with various fiber types. This study evaluated the
      effect of fiber type on the transverse strength of a commercially available
      autopolymerizing resin that is used for repairing prosthesis. The resin was
      reinforced with woven form, chopped form and longitudinal form, and no
      reinforcement was used. Uniform samples were made from autopolymerizing resin. In
      total, twenty-four bar-shaped specimens (60 x 10 x 4 mm) were reinforced with
      glass fibers. Nine specimens were prepared without fiber. A three-point loading
      test was used to measure transverse strength, maximal deflection, and modulus of
      elasticity. The Kruskal-Wallis analysis of variance was used to examine
      differences between the four groups. Although the results of the analysis between
      these groups showed no statistical significances, the transverse strength,
      maximal deflection and modulus of elasticity increased more with fiber than
      without the fiber group. This finding may be of clinical significance. Because
      the addition of fiber reinforcement enhanced the physical properties of the
      processed material, specially woven form glass fiber was superior to the other
      forms.

PMID- 11336389
TI  - Blood-compatible materials: a perspective.
AB  - The interrelation of physicochemical properties with biological interactions at
      the interface to understand blood compatibility of materials in contact with
      blood has been discussed. The bioethics for human experimentation and future
      research outlook has been projected.

PMID- 11336390
TI  - Biology of the anococcygeus muscle.
AB  - The anococcygeus is a smooth muscle tissue of the urogenital tract which, in the
      male, runs on to form the retractor penis. The motor innervation is classically
      sympathetic with noradrenaline as transmitter, but the relaxant parasympathetic
      transmitter has only recently been identified as nitric oxide. Indeed, the
      anococcygeus has provided an extremely useful model with which to probe the
      mechanisms underlying this novel nitrergic system, including the importance of
      physiological antioxidants in maintaining the potency of nitric oxide as a
      neurotransmitter. The cellular mechanisms of contraction and relaxation are
      slowly being clarified, with particular interest in the contribution of
      capacitative calcium entry and the guanylyl cyclase/cyclic GMP system. Many
      questions remain unanswered, however, including the precise physiological role of
      the muscle, the identity of substances released from subcellular vesicles of
      nitrergic nerves, the unusual sensitivity of the tissue to certain peptides
      (oxytocin and urotensin II), and the nature of store-operated channels through
      which calcium enters the cell to maintain contraction.

PMID- 11336391
TI  - Endoplasmic reticulum of animal cells and its organization into structural and
      functional domains.
AB  - The endoplasmic reticulum (ER) in animal cells is an extensive, morphologically
      continuous network of membrane tubules and flattened cisternae. The ER is a
      multifunctional organelle; the synthesis of membrane lipids, membrane and
      secretory proteins, and the regulation of intracellular calcium are prominent
      among its array of functions. Many of these functions are not homogeneously
      distributed throughout the ER but rather are confined to distinct ER subregions
      or domains. This review describes the structural and functional organization of
      the ER and highlights the dynamic properties of the ER network and the mechanisms
      that support the positioning of ER membranes within the cell. Furthermore, we
      outline processes involved in the establishment and maintenance of an anisotropic
      distribution of ER-resident proteins and, thus, in the organization of the ER
      into functionally and morphologically different subregions.

PMID- 11336392
TI  - Apoptosis and syncytial fusion in human placental trophoblast and skeletal
      muscle.
AB  - Skeletal muscle fibers and placental villous trophoblast are the main
      representatives of syncytia in the human. Both syncytia are derived from fusion
      of mononucleated stem cells, show a high degree of differentiation, and have lost
      their generative potency. Consequently, for their growth both depend on fusion of
      additional stem cells. There is evidence that syncytial fusion is directly or
      indirectly related to apoptotic events: As early as in the differentiated stages
      of the mononucleated stem cells, initiation stages of the apoptosis cascade have
      been observed. After syncytial fusion progression of the cascade is retarded or
      blocked by a variety of mechanisms. In this review we emphasize the links between
      apoptosis cascade, differentiation pathways and syncytial fusion. It needs to be
      elucidated whether these processes simply take place in parallel, both temporally
      and spatially, or whether there are causal connections between apoptosis cascade
      and syncytial fusion. Based on recent data obtained for placental villous
      trophoblast, it is tempting to speculate that early molecular mechanisms of the
      apoptosis cascade are involved in differentiation and syncytial fusion. Data
      obtained in skeletal muscles support this assumption and reveal a considerable
      degree of homology in genesis, maintenance and turnover of both tissues.

PMID- 11336393
TI  - Growth and neurotrophic factors regulating development and maintenance of
      sympathetic preganglionic neurons.
AB  - The functional anatomy of sympathetic preganglionic neurons is described at
      molecular, cellular, and system levels. Preganglionic sympathetic neurons located
      in the intermediolateral column of the spinal cord connect the central nervous
      system with peripheral sympathetic ganglia and chromaffin cells inside and
      outside the adrenal gland. Current knowledge is reviewed of the development of
      these neurons, which share their origin with progenitor cells, giving rise to
      somatic motoneurons in the ventral horn. Their connectivities, transmitters
      involved, and growth factor receptors are described. Finally, we review the
      distribution and functions of trophic molecules that may have relevance for
      development and maintenance of preganglionic sympathetic neurons.

PMID- 11336394
TI  - Factors controlling axonal and dendritic arbors.
AB  - The sculpting and maintenance of axonal and dendritic arbors is largely under the
      control of molecules external to the cell. These factors include both substratum
      associated and soluble factors that can enhance or inhibit the outgrowth of axons
      and dendrites. A large number of factors that modulate axonal outgrowth have been
      identified, and the first stages of the intracellular signaling pathways by which
      they modify process outgrowth have been characterized. Relatively fewer factors
      and pathways that affect dendritic outgrowth have been described. The factors
      that affect axonal arbors form an incompletely overlapping set with those that
      affect dendritic arbors, allowing selective control of the development and
      maintenance of these critical aspects of neuronal morphology.

PMID- 11336395
TI  - First BRCA1 and BRCA2 gene testing implemented in the health care system of
      Stockholm.
AB  - The aim of the study was to optimize the criteria for the BRCA1 and BRCA2 gene
      testing and to improve oncogenetic counseling in the Stockholm region. Screening
      for inherited breast cancer genes is laborious and a majority of tested samples
      turn out to be negative. The frequencies of mutations in the BRCA1 and BRCA2
      genes differ across populations. Between 1997 and 2000, 160 families with breast
      and/or ovarian cancer were counseled and screened for mutations in the two genes.
      Twenty-five BRCA1 and two BRCA2 disease-causing mutations were found. Various
      factors associated with the probability of finding a BRCA1 mutation in the
      families were estimated. Age of onset in different generations and other
      malignancies were also studied. Families from our region in which both breast and
      ovarian cancer occur were likely to carry a BRCA1 mutation (34%). In breast-only
      cancer families, mutations were found only in those with very early onset. All
      breast- only cancer families with a mutation had at least one case of onset
      before 36 years of age and a young median age of onset (<43 years). Other
      malignancies than breast and ovarian cancers did not segregate in the BRCA1
      families and surveillance for other malignancies is not needed, in general.
      Decreasing age of onset with successive generations was common and must be taken
      into account when surveillance options are considered.

PMID- 11336396
TI  - Combine-ARMS: a rapid and cost-effective protocol for molecular characterization
      of beta-thalassemia in Malaysia.
AB  - Beta-thalassemia major patients have chronic anemia and are dependent on blood
      transfusions to sustain life. Molecular characterization and prenatal diagnosis
      of beta3-thalassemia is essential in Malaysia because about 4.5% of the
      population are heterozygous carriers for beta-thalassemia. The high percentage of
      compound heterozygosity (47.62%) found in beta-thalassemia major patients in the
      Thalassaemia Registry, University of Malaya Medical Centre (UMMC), Malaysia, also
      supports a need for rapid, economical, and sensitive protocols for the detection
      of beta-thalassemia mutations. Molecular characterization of beta-thalassemia
      mutations in Malaysia is currently carried out using ARMS, which detects a single
      beta-thalassemia mutation per PCR reaction. We developed and evaluated Combine
      amplification refractory mutation system (C-ARMS) techniques for efficient
      molecular detection of two to three beta-thalassemia mutations in a single PCR
      reaction. Three C-ARMS protocols were evaluated and established for molecular
      characterization of common beta-thalassemia mutations in the Malay and Chinese
      ethnic groups in Malaysia. Two C-ARMS protocols (cd 41-42/IVSII #654 and -29/cd
      71-72) detected the beta-thalassemia mutations in 74.98% of the Chinese patients
      studied. The CARMS for cd 41-42/IVSII #654 detected beta-thalassemia mutations in
      72% of the Chinese families. C-ARMS for cd 41-42/IVSI #5/cd 17 allowed detection
      of beta-thalassemia mutations in 36.53% of beta-thalassemia in the Malay
      patients. C-ARMS for cd 41-42/IVSI #5/cd 17 detected beta-thalassemia in 45.54%
      of the Chinese patients. We conclude that C-ARMS with the ability to detect two
      to three mutations in a single reaction provides more rapid and cost-effective
      protocols for beta-thalassemia prenatal diagnosis and molecular analysis programs
      in Malaysia.

PMID- 11336397
TI  - Decision analysis of prenatal testing for chromosomal disorders: what do the
      preferences of pregnant women tell us?
AB  - Current guidelines recommend offering invasive testing for chromosomal disorders
      only to women who are aged 35 or older, or who are at similarly elevated risk (as
      determined by maternal serum and/or ultrasonographic screening). We conducted a
      decision analysis, using preference scores obtained from pregnant women, to
      determine whether current guidelines maximize the health-related quality of life
      of these women. If only miscarriage and chromosomal abnormalities are considered,
      the expected value of testing exceeds that of not testing for women 30 years of
      age or older. However, if a comprehensive range of relevant testing outcomes is
      considered, testing offers a higher expected value than not testing, regardless
      of age. Furthermore, patient preferences for specific testing outcomes play a
      much more substantial role in determining the course of action with the highest
      expected value than does the probability of any of the possible testing outcomes.
      The current age- and risk-based guideline for prenatal diagnosis does not
      maximize expected value and fails to appropriately consider individual patient
      preferences. For counseling purposes, how an individual values the presence and
      timing of fetal chromosomal information should be carefully understood.

PMID- 11336398
TI  - A single strand conformation polymorphism-based carrier test for spinal muscular
      atrophy.
AB  - Spinal muscular atrophy (SMA) is an autosomal recessive disorder with a newborn
      prevalence of 1 in 10,000, and a carrier frequency of 1 in 40-60 individuals. The
      SMA locus has been mapped to chromosome 5q11.2-13. The disease is caused by a
      deletion of the SMN gene, often encompassing other genes and microsatellite
      markers. The SMN gene is present in two highly homologous copies, SMN1 and SMN2,
      differing at five nucleotide positions. Only homozygous SMN1 mutations cause the
      disease. The sequence similarity between the SMN1 and SMN2 genes can make
      molecular diagnosis and carrier identification difficult. We developed a
      sensitive and reliable molecular test for SMN1 carrier identification, by setting
      up a nonradioactive single strand conformation polymorphism (SSCP)-based method,
      which allows for the quantification of the amount of the SMN1 gene product with
      respect to a control gene. The assay was validated in 56 obligate (ascertained)
      carriers and 20 (ascertained) noncarriers. The sensitivity of the test is 96.4%,
      and its specificity, 98%. In addition, 6 of 7 SMA patients without homozygous
      deletions presented with a heterozygous deletion, suggesting a concomitant
      undetected point mutation on the nondeleted SMN1 allele. Therefore, the present
      test is effective for detecting compound hemizygote patients, for testing
      carriers in SMA families, and for screening for SMA heterozygotes in the general
      population.

PMID- 11336399
TI  - Sensitivity and specificity of denaturing high-pressure liquid chromatography for
      unknown protein C gene mutations.
AB  - Screening methods for unknown DNA sequence variations are laborious, expensive,
      and relatively insensitive. To evaluate the sensitivity and specificity of
      denaturing high-pressure liquid chromatography (DHPLC) screening for unknown
      protein C gene (PROC) mutations, we studied 31 PROC-deficient patients. Eleven
      amplimers containing 4 kb of the PROC gene and spanning all exons, splice
      junctions, and the putative promoter and 3'-untranslated regions were amplified
      by PCR for each patient. Each amplimer (n = 341) was sequenced with a
      fluorescence-based method, and screened by DHPLC. Sequencing identified 10 unique
      mutations and three polymorphisms. Combining all mutations and polymorphisms, 227
      amplimers were homozygous wildtype, and 63 and 51 were heterozygous and
      homozygous mutant, respectively. DHPLC screening correctly identified all
      amplimers (100% sensitivity and specificity). DHPLC is a rapid, automated,
      sensitive and specific screening method for unknown mutations within the PROC
      gene, and may be a useful screening method for unknown mutations within other
      genes.

PMID- 11336400
TI  - PCR-RFLP genotyping assay for the Bcl I polymorphism of the beta-fibrinogen gene.
AB  - Polymorphisms of the beta-fibrinogen gene have been shown to affect plasma
      fibrinogen levels and risk of coronary artery disease (CAD). We were interested
      in developing an automated, PCR-based genotyping assay for the purpose of
      exploring relationships between CAD and CAD-associated aortic stiffness and the
      Bcl I allele of the beta-fibrinogen gene. We have developed a rapid PCR-RFLP
      assay for the Bcl I polymorphism of the beta-fibrinogen gene. We carried out
      direct PCR of genomic DNA to facilitate sequencing of the flanking region of the
      beta-fibrinogen gene. Using this new sequence information, primers were designed
      which border the site of the Bcl I polymorphism. One of the primers was labeled
      with a fluorophore to facilitate detection of the fragments. DNA fragment
      analysis was carried out using an automated capillary electrophoresis instrument
      (ABI310). We have developed an improved PCR-RFLP high-sample-throughput assay for
      the semiautomated detection of the Bcl I polymorphism of the beta-fibrinogen
      gene. This assay will support screening of large sample sizes required for
      population studies.

PMID- 11336401
TI  - Prevalence of cystic fibrosis mutations in Israeli Jews.
AB  - The aim of this study was to evaluate the screening policies of cystic fibrosis
      (CF) in the Jewish population. The prevalence of mutations that account for CF in
      Israel have been defined in the past by determining the frequency of CF mutations
      in affected individuals. This study is a population-based study and is,
      therefore, different from previous patient-based studies. We found that the CF
      mutations D1152H, W1089X, and 405 + IG-->A were present in some ethnic groups in
      which no CF patients carrying these mutations were reported. These facts
      necessitate a reevaluation of the screening policy regarding the ethnic groups in
      Israel. We studied 9,430 healthy Jewish Israeli individuals of 36 countries of
      origin. The prevalence of CF mutations was 1:19, 1:19, 1:28, and 1:42 for the
      Ashkenazi, Sephardi, North African, and Eastern Jews, respectively. CF mutations
      were identified in 374 (4.0%) individuals. These included 173 (46.3%) carriers of
      the W1282X mutation; 110 (29.4%) found to carry delF508; 23 (6.1%) who carried
      G542X; 22 (5.9%) who carried 3849 + 10Kb (C-->T; 20 (5.3%) who carried D1152H; 10
      (2.7%) who carried N1303K; 11 (2.9%) who carried 405 + IG-->A; 4 (1.1%) who
      carried W1089X; and one (0.3%) who carried S549R. No carriers were detected for
      the 1717-1G-->A, G85E, and T360K mutations, which were tested for in 7,383,
      1,558, and 41 individuals, respectively.

PMID- 11336402
TI  - Study of the mutation M694V of familial Mediterranean fever in Jews.
AB  - Familial Mediterranean fever (FMF) is a recessively inherited disorder
      characterized by episodes of fever with abdominal pain, pleurisy, or arthritis.
      The familial Mediterranean fever gene, designated MEFV, was recently cloned, and
      the missense mutation M694V accounting for most of the patients with this disease
      was identified. The objective of the present study was to establish frequencies
      of the M694V mutation in three groups of Jews. The subjects studied were 381
      Sephardi, 256 Ashkenazi, and 65 Oriental Jews, all male subjects, previously
      collected for an anthropological study, independent of their FMF status. The
      M694V mutation in the 702 samples was assessed by amplifying genomic DNA with the
      use of primers that selectively amplify the normal or altered DNA sequence of the
      M694V mutation, by the amplification refractory mutation system (ARMS). In our
      sample of Sephardi Jews, the frequency of the M694V mutation is elevated (10.9%),
      and this is also the case for Oriental Jews (9.2%). In our sample of Ashkenazis,
      the M694V allele frequency is very low (0.8%).

PMID- 11336403
TI  - Amplification of a 13.5-kb region of the PKD1 gene containing the 2.5-kb
      polypyrimidine tract in intron 21 facilitates mutation detection in this gene.
AB  - Mutation detection in the PKD1 gene proved to be difficult because two-thirds of
      the gene is reiterated several times on chromosome 16. Long-range PCR has been
      used previously to overcome this limitation, but due to a 2.5-kb polypyrimidine
      tract in intron 21, the screening capacity of the PKD1 gene using this technique
      was hindered. Here we report the measures that we have used to overcome this
      limitation.

PMID- 11336404
TI  - Carrier screening for Gaucher disease in couples of mixed ethnicity.
AB  - With the advent of mutational analysis for Gaucher disease, carrier screening has
      been incorporated into many Jewish genetic disease screening programs.
      Frequencies and mutations for Gaucher disease in non-Jewish populations are less
      well established and the detection rate of carriers are lower. Testing is
      problematic for resolving residual risk in a couple of mixed ethnicity. We report
      the testing choices made by 20 consecutive couples of mixed ethnicity where the
      Ashkenazi Jewish partner was identified to be a Gaucher disease gene carrier.
      Carrier studies of the non-Jewish partner were elected as follows: DNA studies
      alone, 5 (25%); enzymatic assay, 2 (10%); both, 6 (30%); no carrier studies, 7
      (35%). Of the 7 couples not electing carrier studies, one was not in a pregnancy
      and 6 elected prenatal diagnosis in lieu of parental testing by enzymatic
      analysis of amniocytes. One couple elected parental carrier studies as well as
      prenatal diagnosis. All couples electing prenatal Gaucher determination had
      amniocentesis for other indications as well (4, advanced maternal age; 4,
      parental anxiety). We conclude that Gaucher screening is feasible for couples of
      mixed ethnicity if appropriate counseling and testing are offered.

PMID- 11336405
TI  - Identification of new mutations in Israeli patients with X-linked
      adrenoleukodystrophy.
AB  - X-linked adrenoleukodystrophy (ALD) is a peroxisomal disorder characterized by
      impaired peroxisomal betaoxidation of very-long-chain fatty acids (VLCFAs). This
      is probably due to reduced activation of the VLCFAs and results in demyelination
      of the nervous system and adrenocortical insufficiency. The ALD gene is localized
      on Xq28, has 10 exons and encodes a protein of 745 amino acids with significant
      homology to the membrane peroxisomal protein PMP70. Characterizing the disease
      causing mutations is of importance in prenatal diagnosis because 12-20% of women
      who are obligatory carriers show false-negative results when tested for VLCFA in
      plasma. We have analyzed DNA from blood samples of 7 Jewish (5 Sephardi and 2
      Ashkenazi) and 3 Arab Israeli families suffering from ALD. Five missense-type
      mutations were identified: R104H, Y174C, L229P, R401Q, and G512C. A single
      mutation, R464X, was nonsense, and two, Y171 frameshift and E471 frameshift, were
      frameshift. Interestingly, a single mutation was identified in three families of
      Moroccan Jewish descent, probably due to a founder effect.

PMID- 11336406
TI  - Chromosome 10.

PMID- 11336407
TI  - Improved efficiency of mutation detection by denaturing high-performance liquid
      chromatography using modified primers and hybridization procedure.
AB  - The addition of a 20-base GC-clamp to a DNA fragment enabled mutations to be
      detected by denaturing high-performance liquid chromatography (DHPLC) in the
      higher melting domain of the two-domain fragment DYS271. The mutations were
      undetectable in the absence of the GC-clamp. The heteroduplex yield was greatly
      decreased by the presence of mutations in the high melting domain, presumably
      because this region anneals first during cooling, leading to selection of the
      more stable homoduplexes. Suppression of sequence-dependent melting behavior
      using betaine increased the heteroduplex yield almost four-fold. Mutations in the
      high melting domain were detected at 60 degrees C, whereas mutations in the low
      melting domain were detected at 56 degrees C. Computer modeling of the melting
      behavior agreed well with the experimental results, facilitating computer design
      of DHPLC amplicons.

PMID- 11336408
TI  - Laboratory and field assessment of arsenic testing field kits in Bangladesh and
      West Bengal, India.
AB  - High concentrations of arsenic in ground waters in West Bengal and Bangladesh
      have become a major cause for concern in recent years. Given the enormity and the
      severity of the problem of arsenic poisoning, a task of evaluating the
      commercially available arsenic detection field kits for their capabilities was
      undertaken. In the light of the findings, generic specifications were recommended
      which could form the basis for indigenous manufacture of these kits in the
      arsenic affected countries. This article presents the results of the laboratory
      and field evaluation conducted in Bangladesh and West Bengal of five arsenic
      testing field kits. The salient features of the kits, their merits and
      limitations have been brought out. Based on the criteria of kit design, quality
      of chemicals used, colour comparator charts, detection range, time required for
      analysis, cost etc., a comparative ranking of the kits has been made to
      facilitate the choice of the kit to meet specific requirements.

PMID- 11336409
TI  - Monitoring of Ganga water and sediments vis-a-vis tannery pollution at Kanpur
      (India): a case study.
AB  - The leather industry, besides being a major contributor to the Indian national
      economy, is unfortunately also one of the major polluters. The present article
      discusses the influence of the wastes on the physicochemical characteristics of
      the Ganga water and sediments. Two sampling sites have been chosen at Kanpur, the
      first before and the second after the point where tanneries are located. The same
      physicochemical parameters which have been determined in the wastes have been
      monitored at these two sites for two seasons. The results reveal that most
      parameters increase as the river traverses between these two points. The increase
      in values of parameters such as BOD, COD, Cl-, and total solids could be due to
      the domestic wastes just as much as to the tannery wastes. Phenols and sulfides,
      can also come from other sources, but their probability of coming from tanneries
      is higher. However, chromium is one parameter which can primarily be identified
      to originate from the tanneries. The speciation of the sediments for chromium
      reveals that the leakage of chromium into the Ganga is taking place at the second
      site. There is almost a ten fold increase in chromium at the second site as
      compared to the first. At the first site the surface chromium is primarily in the
      residual fraction while at the second site it is in the Fe-Mn oxide fractions.

PMID- 11336410
TI  - Monitoring of atmospheric behaviour of NOx from vehicular traffic.
AB  - In recent years the concern about the behaviour of oxides of nitrogen (NOx: NO,
      NO2) in atmosphere has increased considerably. NOx undergoes various complex
      atmospheric reactions to generate secondary pollutants which are known to cause
      severe adverse effects on human health. This work focuses on the study of
      physical and chemical fate of NOx released in the atmosphere from vehicles, which
      are the main sources of atmospheric NOx. Keeping the objective and standard
      guidelines for monitoring in view, two typical sites near the road with high
      vehicular density were chosen for the study. One site was a relatively cleaner
      area with only vehicles as major source of pollution, and the second site was a
      traffic junction in an industrial region, where pollution levels are amongst the
      highest in Mumbai. Ambient monitoring of NOx was done for 24 hr continuously
      using chemiluminescent NOx analyser. The data was used to analyse temporal and
      spatial variation of NO, NO2 and NOx and their atmospheric chemical reactions.
      The monitoring results show that at larger distance from the road the level of NO
      decreases but the concentration of NO2 which is very harmful remains the same.
      Statistical analysis is conducted to establish the relationship between likely
      change in NO2 concentration as a result of NOx emission changes.

PMID- 11336411
TI  - Characteristics of iron ore tailing slime in India and its test for required pond
      size.
AB  - The physical and chemical nature of the tailing slime depends on milling
      operations and water content in the effluent. The characteristics of the tailings
      dictate the type of disposal facility required. Characteristics of the tailings,
      transportation from beneficiation plants and disposal system are described.
      Studies on tailing slime have been carried out at iron ore mines in Orissa and
      the results are discussed. The tailings contain toxic elements and find their way
      into the water environment. Sedimentation test was carried out on tailings and
      the area required for tailing pond was found to be 3155 m2 in comparison to 10000
      m2 obtained from the use of an empirical equation. Provision of tailing pond for
      the disposal of tailings is a conservation of resources in addition to pollution
      control, and sedimentation test is essential for required pond size calculation.

PMID- 11336412
TI  - Tadpoles assay: its application to a water toxicity assessment of a polluted
      urban river.
AB  - The acute toxicity assay with premetamorphic tadpoles of Bufo arenarum as
      sentinel organism was applied to evaluate the quality of two water samples taken
      from three sites of the Reconquista River, an urban watercourse which is
      recipient of both untreated industrial effluents and domestic wastes. The results
      of the 96 hr bioassays were compared with the physicochemical parameters
      determined in the samples. Mortality rates in each sample were compared using the
      Bonferroni's test and a stepwise regression analysis of mortality and
      physicochemical parameters was done. In this way, it was possible to build up
      consistent descriptive models which showed that pH, Cl- Cd2+ and Cu2+
      concentrations in the river water were significant independent variables and
      might explain, under the experimental conditions, the recorded toxicity effects
      of the tested samples. Because of its simplicity, low cost and reliability it was
      suggested the tadpoles bioassay be included in the set of tests used in
      integrated program of freshwater pollution.

PMID- 11336413
TI  - Cadmium and lead levels in fish (Tilapia nilotica) tissues as biological
      indicator for lake water pollution.
AB  - Cadmium and lead were determined in different tissues (muscle, gill, stomach,
      intestine. liver, vertebral column and scales) of Tilapia nilotica from the High
      Dam Lake, Aswan (Egypt) to assess the lake water pollution with those toxic
      metals. Fish samples were chosen from different ages and weights to be analyzed
      along with samples of the aquatic plant (Najas armeta), sediment and lake water.
      The results showed that cadmium and lead concentrations were higher in fish
      scales and vertebral column than in the other parts of the fish. Cadmium and lead
      levels in High Dam lake water and fish (Tilapia nilotica) were a result of the
      pollution which uptakes from aquatic plants, sediments and gasoline containing
      lead that leaks from fishery boats. Tilapia nilotica fish was used as a good bio
      assay indicator for the lake pollution with cadmium and lead. The fish muscles in
      this study were in the safety baseline levels for man consumption.

PMID- 11336414
TI  - A study on transfer factors of 60Co and 65Zn from soil to plants in the tropical
      environment of Bangladesh.
AB  - Soil to plant transfer factor (TF) of 60Co and 65Zn was determined from
      radioisotope experiments on plants grown in pots under outdoor ambient tropical
      conditions for three growing seasons (1995-1998). The TFs were obtained for
      different plants/crops such as, rice, bean, peanuts pineapple, cabbage, tomato,
      spinach and grass. The average TF values of 60Co are found to be 0.087. 0.15,
      0.12, 0.67, 0.28, 0.79, 1.03 and 0.34 respectively for the above mentioned
      plants/crops. In case of 65Zn, the average TF values are found to be 2.24, 1.17.
      0.89, 1.09, 0.78, 1.34, 2.92 and 1.78, respectively, for the above mentioned
      plants/crops. The data will be useful to assess the radiation exposure to man
      associated with the releases of radionuclides from nuclear facilities by means of
      radiological assessment models that require transfer factors as input parameters
      to predict the contamination of radionuclides in foodchain.

PMID- 11336415
TI  - A review of the role of inhaled corticosteroids in the treatment of acute asthma.
AB  - Systemic corticosteroids (CSs) are generally accepted as treatment for acute
      exacerbations of asthma. In contrast, inhaled corticosteroids (ICs) have been
      used for the long-term management of asthma but are not widely accepted for the
      treatment of asthma exacerbations. The onset of action of ICs in acute asthma
      begins in 1 hour. In patients with mild to moderate exacerbation, administration
      of high-dose ICs may decrease the need for hospital admission and the number of
      symptomatic days.

PMID- 11336416
TI  - Are follow-up throat cultures necessary when rapid antigen detection tests are
      negative for group A streptococci?
AB  - The frequency of obtaining false-negative Group A Streptococcal (GAS) rapid
      antigen detection (RAD) tests utilizing currently available kits in a private
      practice setting and the cost effectiveness of requiring follow-up throat
      cultures were studied. Laboratory records of the Elmwood Pediatric Group (EPG),
      Rochester, NY, were retrospectively reviewed to identify all patients with
      pharyngeal RAD tests for GAS performed from January 1996 through May 1999. From
      January 1996 through October 1997 (study period 1), EPG physicians used either a
      RAD test or a throat culture to identify GAS; from November 1997 through May 1999
      (study period 2), RAD tests were used as the primary test on all patients. Rapid
      antigen detection test negative results were confirmed with culture. During the 3
      year study 11,427 RAD tests were performed. 8,385 (73.4%) were negative and 3,042
      (26.6%) were positive. In study period 1, 3,547 (73.2%) were negative and 1,299
      (26.8%) were positive; in study period 2 4,837 (73.5%) were negative and 1,743
      (26.5%) were positive. Of the 8,385 negative tests, 8,234 (98.2%) were followed
      up with throat cultures. Of these, 200 (2.4%) were identified to have been
      negative RAD tests that were throat culture positive (132 [3.8%] of 3,474 in
      study period 1 and 68 [1.4%] of 4,764 in study period 2). A cost analysis was
      performed for study period 2, which showed that abandoning throat culture
      confirmation would generate a cost saving of $13,521 per year to the practice.
      Throat culture confirmation of RAD test negative results in pharyngitis patients
      may not be medically necessary for most patients with currently available RAD
      tests and is costly.

PMID- 11336417
TI  - Injury reduction and bounce characteristics of safety baseballs and acceptability
      by youth leagues.
AB  - The only reasonable way to reduce the potential for ball-related youth baseball
      injuries sustained by the defensive players (the majority of ball-related
      injuries) is to make the ball less injurious. The American Academy of Pediatrics'
      1994 statement on youth baseball injuries in this regard reads, "Consideration
      should be given to utilizing low-impact NOCSAE-approved baseballs and softballs
      for children 5 to 14 years of age, if these balls demonstrate satisfactory
      playing characteristics and reduce injury risk. A variety of studies should be
      undertaken to determine the efficacy of low-impact balls in reducing serious
      impact injuries." The purpose of this study, in accordance with this AAP policy,
      is to investigate the following: A) injury reduction potential of softer
      baseballs, B) their bounce characteristics, and C) their acceptability by youth
      leagues. Six simple injury models were studied, baseball bounce characteristics
      were analyzed, and attitudes of safety baseballs among statewide Little League
      district presidents were surveyed. Injury models demonstrated less injury
      potential with safety baseballs compared to that with standard hard baseballs.
      Safety baseballs bounced higher after vertical drops and slow throws, but during
      fast throws (with the greatest injury potential), the bounce heights were similar
      for all ball types. Of 27 survey cards sent out, 13 were returned. While 9
      respondents indicated that they were already using safety baseballs for the
      younger players, none of the 13 respondents indicated that they were planning to
      expand the use of safety baseballs in their leagues. In conclusion, safety
      baseballs are less injurious in these models. The bounce characteristics of
      safety baseballs are satisfactory. Youth baseball league officials are not very
      willing to expand the use of safety baseballs. We recommend using safety
      baseballs as a standard for all youth baseball leagues because these balls are
      safer.

PMID- 11336418
TI  - A kinder, gentler baseball.

PMID- 11336419
TI  - Knowledge of concussion guidelines among practitioners caring for children.
AB  - The objective of this study in Rochester, NY was to determine clinicians'
      knowledge of the Colorado Medical Society Guidelines (CMSG) on return to contact
      sports after a concussion. A survey was mailed to 1,140 pediatric, family
      practice, and emergency physicians, as well as 302 pediatric and family practice
      nurse practitioners in the Rochester, NY, area. Participants were given 3
      hypothetical concussion scenarios and asked to pick 1 of 4 multiple-choice time
      intervals for when they would advise return to contact sports. Answers were
      compared with the latest version of the CMSG. The survey response rate was 57%.
      Only 7.6% responded correctly for Grade 1 concussion scenario, 56% for the Grade
      2 scenario, and 28% for the Grade 3 scenario. Only 5.6% listed the CMSG as the
      source of the return-to-play advice they gave. Thus, respondents' knowledge of
      the CMSG was low, with few giving return-to-play advice consistent with the CMSG
      and even fewer acknowledging the CMSG as the source of such advice. Improving the
      availability of the CMSG may improve clinicians' knowledge and use of these
      guidelines.

PMID- 11336420
TI  - An 11-year-old girl with chronic abdominal pain.

PMID- 11336421
TI  - Intravenous bisphosphonate for hypercalcemia accompanying subcutaneous fat
      necrosis: a novel treatment approach.

PMID- 11336422
TI  - Seizure occurrence in children diagnosed with ADHD.

PMID- 11336423
TI  - Dietary medium-chain triglycerides: a source of urinary dicarboxylic acids and
      diagnostic confusion.

PMID- 11336424
TI  - Epstein-Barr virus cerebellitis presenting as obstructive hydrocephalus.

PMID- 11336425
TI  - Obstructive laryngotracheitis secondary to gentian violet exposure.

PMID- 11336426
TI  - Bilateral kidney duplication in familial Noonan's syndrome.

PMID- 11336427
TI  - Synovial effusion in a patient with anorexia nervosa.

PMID- 11336428
TI  - Intrauterine contraception--what now and what next?
AB  - Rising each year by around 85 million, we have started this millennium with over
      6,000 million, mostly utterly destitute, human beings on a finite planet. We will
      never meet human needs without stabilizing human numbers. In the sexual arena,
      all human beings (but especially the males of the species) are very bad at using
      their brains and their genitalia at the same time, i.e. putting the knowledge in
      their head about risks of conception or of sexually transmitted infections into
      appropriate preventive action when sexually aroused! Therefore, a very useful
      criterion for choice of methods all through the various stages of reproductive
      life is 'forgettability'. This is a great 'plus' point for the intrauterine
      route, especially the levonorgestrel intrauterine system (LNG-IUS). Its main
      contraceptive effects are local, by endometrial suppression and changes to the
      cervical mucus and uterotubal fluid, which impair sperm migration. The blood
      levels of levonorgestrel are about one-quarter of the peak levels in users of the
      progestin-only pill, and so gestagenic symptoms are uncommon and ovarian function
      is little altered. Most women continue to ovulate and, in the remainder,
      sufficient estrogen for health is produced from the ovary even if they become
      amenorrheic, as many do; this is primarily a local end-organ effect and should be
      seen as a benefit. Postmenopausal estradiol levels have not been detected, even
      in those who have no uterine bleeding. Although usable by selected nulliparae,
      the LNG-IUS is a particularly good choice for the parous woman, for whom I
      maintain it represents the future already here, which is not recognized by many
      providers. It has unsurpassed efficacy; 99.5% of women have not conceived after 5
      years of use. Return of fertility is rapid and appears to be complete. Combining
      the best features of hormonal and intrauterine contraception without most ofthe
      problems of either, it fundamentally 'rewrites the textbooks' about intrauterine
      devices. Its gynecological benefits are impressive: the LNG-IUS user can expect a
      dramatic reduction in amount and, after the first few months, in duration of
      blood loss. Dysmenorrhea is also greatly benefited, in most cases. In summary,
      the LNG-IUS fulfils many of the criteria for an 'ideal' contraceptive. Adverse
      side-effects are few and, in general, they are not in the category 'hazardous'.
      Regarding the inconvenience of the first weeks of light post-insertion bleeding
      and the early-phase low incidence ofsteroidal side-effects, forewarned is
      forearmed!

PMID- 11336429
TI  - The levonorgestrel intrauterine system: more than a contraceptive.
AB  - Levonorgestrel can be released directly into the uterine cavity, where it causes
      pronounced endometrial suppression, although the dose of hormone is so low that
      the effect on ovarian function is negligible. The levonorgestrel-releasing
      intrauterine system (LNG-IUS) consists of a plain Nova-T device with a silastic
      reservoir attached to the vertical arm. The silastic reservoir is impregnated
      with levonorgestrel and is covered with a rate-limiting silastic membrane. The
      release rate oflevonorgestrel is approximately 20 microg/24 h for at least 5
      years. The contraceptive efficacy of the LNG-IUS has been studied in a
      randomized, comparative trial over 5 years. A total of 1,821 women were fitted
      with the LNG-IUS and were compared with 937 women who were using the copper
      releasing device, Nova-T. The continuation rates were 46.9 for the LNG-IUS and
      44.5 for the Nova-T. The cumulative gross pregnancy rates were 0.5 for the LNG
      IUS and 5.9 for the Nova-T. The Pearl index after 5 years was 0.09/100 woman
      years for the LNG-IUS and the ectopic pregnancy rate was 0.02/100 woman-years.
      There were less withdrawals because of bleeding problems and pelvic inflammatory
      disease in the LNG-IUS group compared with the Nova-T group, but there were more
      withdrawals because of hormonal side-effects and absence of bleeding. There were
      no differences in the return of fertility after removal of the LNG-IUS and the
      Nova-T. All women will notice a change in their bleeding pattern after the LNG
      IUS has been inserted and some will initially experience many days of spotting.
      It is extremely important to counsel women about the changes in bleeding pattern
      that will occur with the LNG-IUS before the system is fitted. One of the
      advantages of the LNG-IUS is that menstrual blood loss will decrease (and
      therefore hemoglobin levels will increase), which means that the LNG-IUS is one
      of the most effective reversible long-term treatments of idiopathic menorrhagia.
      The LNG-IUS can be used successfully throughout the reproductive period for
      effective contraception and treatment of menorrhagia. In addition, this system
      provides endometrial protection. Women who suffer from climacteric symptoms while
      they are using the LNG-IUS can be given estrogen to relieve their symptoms.

PMID- 11336430
TI  - Sixty thousand woman-years of experience on the levonorgestrel intrauterine
      system: an epidemiological survey in Finland.
AB  - OBJECTIVE: An epidemiological survey was carried out in Finland to establish the
      performance of the levonorgestrel intrauterine system (LNG-IUS) in a large
      population of women regularly using the system for contraception. STUDY DESIGN:
      All women who had LNG-IUS inserted between 1990 and 1993 were sent a
      questionnaire with questions about general health status, reproductive and
      contraceptive history and gynecological problems and a set of questions about
      their experience on the LNG-IUS. RESULTS: The women who had a LNG-IUS inserted
      between April 1990 and December 1993 were asked to participate in an
      epidemiological survey. At the insertion visit, the women were asked to fill in a
      questionnaire, to consent to further use of the information by signing their
      initials and to return the questionnaire to the manufacturer. The number of
      returned forms was 23,885. The names and addresses of these women were acquired
      from the National Register and a questionnaire with 75 questions was sent to
      them. Of the questionnaires, 75% were returned. Experience covered 58,600 woman
      years. The mean age of the users of the LNG-IUS was 40 years. Most of them
      (99.3%) were parous, most often with two or three children. The cumulative 5-year
      Pearl index was 0.18 and there were 108 pregnancies in the study population
      during the use of the LNG-IUS. The continuation rates for 1, 2, 3, 4 and 5 years
      were 0.94, 0.87, 0.82, 0.76 and 0.65, respectively. Removal before the full 5
      years was most common among the youngest age group. Bleeding disorders,
      infections and pain during LNG-IUS use were associated with the highest risk for
      discontinuation. The risk of premature removal was markedly diminished among
      women with totally or occasionally missed periods. CONCLUSIONS: The response rate
      to the survey was high and the sample studied was exceptionally large. The
      continuation rate of LNG-IUS was high up to 5 years. The symptoms associated with
      premature removal agreed with results from earlier randomized studies of the LNG
      IUS.

PMID- 11336431
TI  - The levonorgestrel intrauterine system: the benefits of reduced bleeding.
AB  - The levonorgestrel intrauterine system (LNG-IUS) offers a new therapeutic concept
      that combines a highly efficient contraceptive with a treatment that reduces
      menstrual blood loss in both normal women and those with menorrhagia. Initially
      developed to decrease the risk of expulsion of the intrauterine contraceptive
      device by reducing myometrial contractility, recent clinical studies have shown
      that the LNG-IUS provides excellent contraception without many of the adverse
      effects associated with the conventional intrauterine contraceptive device. The
      main mechanism of action of the LNG-IUS appears to be at the level of the
      endometrium, where the high dose of local progestogen causes decidualization,
      epithelial atrophy and direct vascular changes. Whilst some women experience
      systemic hormonal effects, circulating concentrations of levonorgestrel are low
      in comparison to those seen after the levonorgestrel progestogen-only pill. The
      LNG-IUS results in a dramatic reduction in menstrual blood loss. In turn, this
      has led researchers to investigate the LNG-IUS as an alternative to surgery for
      the treatment of dysfunctional uterine bleeding, uterine fibroids and
      adenomyosis. The system has also been used as a means of delivering progestogen
      for endometrial protection in postmenopausal hormone replacement regimens. The
      main side-effect of the LNG-IUS is irregular breakthrough bleeding. This is most
      common in the first 6 months after insertion. Detailed counselling is crucial to
      explain this anticipated effect, in order to reduce unnecessary discontinuation
      of treatment. After 6 months' treatment with the LNG-IUS, 20% of women become
      amenorrheic, rising to 50% after 5 years. Again, it is important to explain that
      this is an expected phenomenon, that it is not related to disorders of the
      hypothalamic-pituitary-ovarian axis, and that this 'bleed-free' status might
      indeed be viewed as a positive feature in its own right.

PMID- 11336433
TI  - Medical legal issues in allogeneic blood transfusion.
AB  - PURPOSE: To review what we, as physicians, should know about informed consent
      when ordering transfusions for our patients. SOURCE: In December of 1984 a
      patient having coronary artery bypass surgery was transfused with a human
      immunodeficiency virus (HIV) positive blood component. Sixteen years later, the
      patient died of acquired immunodeficiency syndrome (AIDS)-related pneumonia. This
      case led to the Krever Commission of Inquiry on the Blood System in Canada.
      PRINCPAL FINDINGS: Physicians should be aware of the medical/legal issues of
      ordering transfusion of blood or blood products. Central to this is the principle
      that "Every human being of adult years and of sound mind has the right to
      determine what shall be done with his or her own body". Justice Krever
      recommended physicians should obtain informed consent for the administration of
      blood and blood products. This should be documented in the chart as well as
      reported in the discharge summary and in a letter to the referring physician.
      Informed consent must be voluntary, the patient must have capacity to consent and
      must be properly informed. A patient has the right to refuse treatment even when
      it is clear that the treatment is necessary to preserve life or health. However,
      a refusal must also be informed and carefully documented. CONCLUSION: Physicians
      should seriously consider abiding by the recommendations of the Krever
      Commission. Though not yet official standards of care, physicians following these
      recommendations will likely avoid successful litigation regarding allogeneic
      blood transfusions.

PMID- 11336432
TI  - Non-pharmacological strategies for blood conservation in cardiac surgery.
AB  - PURPOSE: Of all surgical specialties, cardiac operations are most often
      associated with coagulopathy, blood loss, and the need for transfusions. This not
      only represents a major burden on blood procurement and banking organizations at
      all levels, but also constitutes a risk for each patient receiving allogeneic
      blood products. This paper reviews current non-pharmacological strategies aimed
      at decreasing blood use in patients undergoing cardiac surgery. SOURCE: The
      literature pertaining to each blood conservation strategy was searched, reviewed,
      and appraised. Meta- analyses were also consulted and their results complemented
      with subsequent reports when available. PRINCIPAL FINDINGS: Preoperative
      autologous donation programs are effective in decreasing allogeneic transfusions,
      but are costly and applicable to elective patients only. Off-pump
      revascularization strategies also appear to decrease transfusion requirements in
      suitable patients. The effectiveness of acute normovolemic hemodilution,
      retrograde autologous priming, small volume cardiopulmonary bypass circuits,
      platelet-rich plasmapheresis, alternative heparin strategies, and postoperative
      cell salvage are more difficult to appraise as a high proportion of available
      studies suffer from lack of transfusion guidelines or the absence of blinding.
      Biological glues, surgical adhesives, and postoperative increases in positive end
      expiratory pressure (PEEP) have no demonstrated efficacy. CONCLUSION: The
      applicability or effectiveness of many of these modalities remains controversial
      and more studies are needed before they may be employed routinely in cardiac
      surgical patients. The judicious use of rational transfusion guidelines may still
      be the simplest and most cost-effective means of blood conservation today.

PMID- 11336434
TI  - Pharmacological strategies for blood conservation in cardiac surgery:
      erythropoietin and antifibrinolytics.
AB  - PURPOSE: We review the clinically important benefits of the two principal
      pharmacological strategies, erythropoietin (EPO) and antifibrinolytics (aprotinin
      and lysine analogues), to decrease transfusion of allogeneic blood products (ABP)
      during and after cardiac surgery. SOURCE: Articles were selected from an ongoing
      review of the literature, with special attention to meta-analyses dealing with
      EPO and/or antifibrinolytics and cardiac surgery. PRINCIPAL FINDINGS: The few
      studies available include a number of patients insufficient to allow definitive
      conclusions on the benefits of EPO in cardiac surgery. Further studies are
      required to determine the optimal dose of EPO and to compare its cost
      effectiveness with other blood sparing strategies in this context. Both aprotinin
      and lysine analogues effectively decrease ABP transfusions and the incidence of
      re-thoracotomy. In addition, high-dose aprotinin reduces cerebrovascular
      morbidity and mortality after cardiopulmonary bypass. Several mechanisms have
      been put forward to explain these beneficial effects, some of which could well be
      common to all antifibrinolytics. The clinical benefits of aprotinin's unique anti
      inflammatory effect are not entirely clear but the finding that it reduces the
      incidence of stroke and death is certainly a major argument in favor of its
      utilization. Yet, we have to ensure that aprotinin's benefits are not offset by
      side-effects such as allergy. CONCLUSIONS: We still need large scale studies to
      definitely confirm the benefits and exclude the deleterious effects of these
      drugs on outcomes other than ABP requirements. At present, aprotinin is the only
      agent that has been shown to reduce the risk of cerebrovascular accident and
      mortality after cardiac surgery in adults.

PMID- 11336435
TI  - Oxygen therapeutics--current concepts.
AB  - PURPOSE: In an effort to develop agents that enhance the oxygen-delivery
      capability of blood without the risks associated with allogeneic blood
      transfusions, several products are undergoing development and clinical trials.
      These oxygen transport agents can be divided into two main groups,
      perfluorocarbon (PFC) emulsions and modified hemoglobin solutions. SOURCE:
      Articles from the literature on the development and clinical trials of oxygen
      therapeutic agents were reviewed. PRINCIPAL FINDING: PFCs are synthetic
      fluorinated hydrocarbons that increase dissolved oxygen in the fluid phase of the
      blood without binding the oxygen molecule. They enhance oxygen delivery
      significantly and may be used to augment the technique of intraoperative
      autologous donation. Two PFC products have been tested in Phase III clinical
      trials. Hemoglobin-based oxygen carriers (HBOCs) are either cross-linked or
      microencapsulated hemoglobin molecules. Modification of the human hemoglobin
      molecule with intra- and inter-molecular cross-linking eliminates renal toxicity
      and improves the oxygen dissociation characteristics of the molecule. These
      modifications are necessary because stroma-free hemoglobin (Hb) does not release
      oxygen in the physiologic range and dissociates into dimers which can be rapidly
      filtered by the kidney, leading to renal toxicity. In addition to human Hb,
      bovine hemoglobin is another source of raw material for HBOC products.
      Recombinant human Hb has also been produced, using an E. coli expression system,
      for HBOC manufacturing. Four cross-linked hemoglobin products have been tested in
      Phase III clinical trials. CONCLUSION: While no product has yet been approved for
      clinical use, preliminary studies with oxygen therapeutics show promising
      results, with effective oxygen carrying capacity and acceptable side effect
      profiles. In the future, the formation of a hybrid product which combines the
      best features from several of the products currently undergoing development may
      yield the ideal oxygen therapeutic agent.

PMID- 11336436
TI  - Safety and efficacy of o-raffinose cross-linked human hemoglobin (Hemolink) in
      cardiac surgery.
AB  - PURPOSES: There are currently two major classes of oxygen therapeutics:
      hemoglobin based oxygen carriers (HBOCs) and synthetic perfluorocarbons (PFCs).
      This review focuses on the use of o-raffinose cross-linked human hemoglobin (Hb
      raffimer) in cardiac surgery. SOURCE: The literature on HBOCs was reviewed and
      the development and clinical trials on Hb raffimer were outlined. PRINCIPAL
      FINDING: The benefits of HBOCs include avoidance of known viruses, pathogens and
      cross-matching; increased stability and storage time; and efficient oxygen
      delivery to tissues. The limitations of HBOCs include binding the endogenous
      vasodilator, nitric oxide, thereby resulting in transient hypertension,
      esophageal dysfunction and abdominal discomfort. The short half-lives of these
      products makes them best suited to situations of acute anemia. Hb raffimer is
      prepared from outdated red blood cells, cross-linked with o-raffinose, a
      polyaldehyde obtained through the oxidation of the trisaccharide raffinose. The
      Hb is covalently cross-linked (beta-beta) within the 2,3 DPG binding pocket to
      form a stable 64 kDa tetramer. At this time, a total of over 500 patients have
      been enrolled and more than 300 patients have been treated with Hb raffimer.
      Preliminary analysis of data from recent Phase II & III clinical trials of Hb
      raffimer in routine coronary artery bypass grafting surgery suggest that the
      product is well tolerated and may facilitate avoidance of allogeneic blood
      product transfusion in this surgical setting. CONCLUSION: The converging evidence
      from clinical studies with HBOCs has demonstrated that these products have the
      potential to provide hemoglobin and oxygen carrying capacity to tissues in times
      of acute anemia during surgery. It is anticipated that Hb raffimer will be used
      to facilitate intraoperative autologous donation and emerge as an important
      alternative to allogeneic blood transfusion during cardiac surgery.

PMID- 11336437
TI  - Blood transfusion in cardiac surgery.
AB  - PURPOSE: Cardiothoracic surgeons and anesthesiologists have had a long-standing
      interest in the proper use of transfusion therapy for their patients. SOURCE: We
      review the literature on variability and patterns of transfusion practices in
      cardiac surgery, on the infectious and noninfectious risks of transfusions, and
      on the impact of new technologies. Data from the cardiac surgery registry at the
      Beth Israel Deaconess Medical Center are presented. PRINCIPAL FINDINGS: Blood
      conservation strategies such as intraoperative and postoperative salvage,
      hemodilution and drug treatments to minimize bleeding were developed for cardiac
      patients. Despite this work, there is significant variation in transfusion
      practices among cardiac surgery centers. Improved donor selection and screening
      by increasingly sophisticated tests have dramatically reduced the risks of
      transfusion-transmitted disease. However, the increasing acuity and complexity of
      the condition of patients having surgery, as well as the availability of safer
      allogeneic blood, have resulted in an increasing number of transfusions to
      patients undergoing cardiac operations. The majority of patients having open
      heart surgery receive allogeneic blood. Blood conservation strategies continue to
      be important because of the non-infectious hazards of transfusion such as
      mistransfusion, transfusion-related acute lung injury, circulatory overload and
      others. Newer technologies (such as minimally invasive and off-pump surgery)
      promise to favourably affect blood use. CONCLUSION: Issues such as the cost of
      blood, limited availability and the potentially harmful effects of transfusion
      dictate continued research and the development of methods to appropriately
      minimize transfusion to patients having cardiac surgery.

PMID- 11336438
TI  - Pharmacologic inhibition of poly(ADP-ribose) polymerase is neuroprotective
      following traumatic brain injury in rats.
AB  - The nuclear enzyme poly(ADP-ribose) polymerase (PARP), which has been shown to be
      activated following experimental traumatic brain injury (TBI), binds to DNA
      strand breaks and utilizes nicotinamide adenine dinucleotide (NAD) as a
      substrate. Since consumption of NAD may be deleterious to recovery in the setting
      of CNS injury, we examined the effect of a potent PARP inhibitor, GPI 6150, on
      histological outcome following TBI in the rat. Rats (n = 16) were anesthetized,
      received a preinjury dose of GPI 6150 (30 min; 15 mg/kg, i.p.), subjected to
      lateral fluid percussion (FP) brain injury of moderate severity (2.5-2.8 atm),
      and then received a second dose 3 h postinjury (15 mg/kg, i.p.). Lesion area was
      examined using Nissl staining, while DNA fragmentation and apoptosis-associated
      cell death was assessed with terminal deoxynucleotidyl-transferase-mediated
      biotin-dUTP nick end labeling (TUNEL) with stringent morphological evaluation.
      Twenty-four hours after brain injury, a significant cortical lesion and number of
      TUNEL-positive/nonapoptotic cells and TUNEL-positive/apoptotic cells in the
      injured cortex of vehicle-treated animals were observed as compared to uninjured
      rats. The size of the trauma-induced lesion area was significantly attenuated in
      the GPI 6150-treated animals versus vehicle-treated animals (p < 0.05). Treatment
      of GPI 6150 did not significantly affect the number of TUNEL-positive apoptotic
      cells in the injured cortex. The observed neuroprotective effects on lesion size,
      however, offer a promising option for further evaluation of PARP inhibition as a
      means to reduce cellular damage associated with TBI.

PMID- 11336439
TI  - Differential cellular accumulation of connective tissue growth factor defines a
      subset of reactive astrocytes, invading fibroblasts, and endothelial cells
      following central nervous system injury in rats and humans.
AB  - In brain injury, the primary trauma is followed by a cascade of cellular and
      molecular mechanisms resulting in secondary injury and scar formation.
      Astrogliosis and expression of transforming growth factor beta (TGF-beta) are key
      components of scar formation. A cytokine mediating the effects of TGF-beta is
      connective tissue growth factor (CTGF), a fibrogenic peptide encoded by an
      immediate early gene with suggested roles in tissue regeneration and aberrant
      deposition of extracellular matrix. In order to investigate CTGF in traumatic
      lesions, we evaluated 20 human brains with traumatic brain injury (TBI) and 18
      rat brains with stab wound injury. Compared to remote areas and unaltered control
      brains, CTGF+ cells accumulated in border zones of the traumatic lesion site (p <
      0.0001). In the direct peri-lesional rim, CTGF expression was confined to
      invading vimentin+, GFAP- fibroblastoid cells, endothelial and smooth muscle
      cells of laminin+ vessels, and GFAP+ reactive astrocytes. In the direct peri
      lesional rim, CTGF+ astrocytes (>80%) co-expressed the activation associated
      intermediate filaments nestin and vimentin. In injured rat brains, numbers of
      CTGF+ cells peaked at day 3 and 7 and decreased to almost base level 3 weeks
      postinjury, whereas in humans, CTGF+ cells remained persistently elevated up to 6
      months (p < 0.0001). The restricted accumulation of CTGF+-reactive astrocytes and
      CTGF+ fibroblastoid cells lining the adjacent laminin+ basal lamina suggests
      participation of these cells in scar formation. Furthermore, peri-lesional
      upregulation of endothelial CTGF expression points to a role in blood-brain
      barrier function and angiogenesis. In addition, CTGF appears to be a sensitive
      marker of early astrocyte activation.

PMID- 11336440
TI  - Quantitative analysis of microvascular alterations in traumatic brain injury by
      endothelial barrier antigen immunohistochemistry.
AB  - Endothelial barrier antigen (EBA) is a protein triplet located in the plasma
      membrane of microvascular endothelium and selectively expressed in the normal
      nervous system. In this study, microvascular alterations following traumatic
      brain injury were studied using EBA immunohistochemistry. Anesthetized,
      physiologically regulated, normothermic Sprague-Dawley rats received moderate
      (1.5-2.0 atm) parieto-occipital parasagittal fluid-percussion traumatic brain
      injury (TBI). Control rats were subjected to similar anesthesia and physiological
      monitoring. Seven days after operative procedures, brains were perfusion-fixed,
      and coronal sections were reacted for EBA immunohistochemistry using a monoclonal
      antibody to rat EBA. Selected sections were reacted for isolectin B4
      histochemistry. Computerized image analysis was used to compute numbers of EBA
      immunopositive vascular profiles and mean vascular profile areas. In control
      brains, virtually all brain microvessels were clearly and positively
      immunostained, and antibody binding was specific for blood vessels. In rats with
      TBI, EBA immunoreactivity was greatly reduced in the zone of cortical contusion.
      Within the core contusion, fractional areas occupied by vascular profiles were
      markedly reduced (on average, by 57%), vascular profile counts were diminished,
      and lectin histochemistry revealed a robust inflammatory response with abundant
      macrophages. Taken together, these findings were thought to indicate frank
      microvascular destruction. At adjacent peri-contusional sites, the intensity of
      EBA immunostaining was also diminished; and vascular profile counts were reduced
      at adjacent cortical sites and homologous contralateral sites. The latter
      findings were interpreted as sublethal microvascular alterations possibly related
      to cerebral edema. The present results confirm that EBA is a specific
      immunohistochemical marker of normal central nervous system microvessels; that it
      is suitable for use in formaldehyde-fixed material; and that it is useful in
      quantitatively assessing microvascular alterations observed at contusional, peri
      contusional and more remote sites following traumatic brain injury.

PMID- 11336441
TI  - Cellular inflammatory response associated with breakdown of the blood-brain
      barrier after closed head injury in rats.
AB  - This study reports a widespread microglial response characterized by an
      upregulation of surface antigens, such as complement type 3 receptors (CR3) and
      major histocompatibility complex (MHC) class II antigens on these cells following
      closed head injury. Increased expression of CR3 (OX-42) and MHC class II antigens
      (OX-6) was observed in rats killed at 1, 3, and 5 days after injury. Intense OX
      42 immunoreactivity was observed in microglial cells throughout the brain with a
      smaller number of them being OX-6 positive. In addition to microglial reaction,
      astrocytic activation reflected in cellular hypertrophy and increased
      immunoreactivity for glial fibrillary acidic protein (GFAP) was observed at 5
      days after head injury. Together with the above, a diffuse perivascular and
      intraneuronal immunostaining for immunoglobulin G (IgG) was observed primarily in
      the cerebral cortex. This was accompanied by an enhanced expression of both
      endothelial nitric oxide synthase (eNOS) in blood vessels and inducible nitric
      oxide synthase (iNOS) in brain macrophages. In rats subjected to closed head
      injury followed by a single intraperitoneal (i.p.) injection of rhodamine
      isothiocyanate (RhIc), seepage of the fluorescent dye into the neuropil was
      observed. This had resulted in the labelling of the cortical neurons clearly
      demonstrating a breakdown of the blood-brain barrier (BBB). In the latter, it is
      conceivable that the ensuing leakage of plasma immunoglobulins and other serum
      derived materials could induce the expression of MHC class II antigens on
      microglia. The mechanism causing the BBB dysfunction is not clear, although
      present results suggest that excessive release of nitric oxide (NO) may be a
      contributory factor. The widespread activation of microglia in rats after head
      injury suggests their involvement in increased endocytosis and immunological
      responses.

PMID- 11336442
TI  - Reduction of pathological and behavioral deficits following spinal cord contusion
      injury with the selective cyclooxygenase-2 inhibitor NS-398.
AB  - Spinal cord injury (SCI) results in loss of locomotor function and development of
      abnormal chronic pain syndromes (mechanical allodynia, thermal hyperalgesia).
      Following injury, secondary mechanisms including release of excitatory amino
      acids, inflammation and lipid peroxidation damage neural cells through release of
      cytotoxic free radicals. We hypothesized that selective inhibition of
      cyclooxygenase-2 (COX-2), an inducible inflammatory mediator, would decrease
      tissue damage and subsequently reduce locomotor deficits and development of
      chronic central pain syndromes after injury. Fifteen minutes prior to receiving
      T13 spinal segment spinal cord contusion injury, 200-225-g male Sprague-Dawley
      rats received either vehicle (0.5 ml 1:1 v/v DMSO/saline, i.p., n = 20) or the
      selective COX-2 inhibitor NS-398 (5 mg/kg in DMSO/saline v/v, i.p., n = 20).
      Locomotor function via the BBB scale, and nociceptive behaviors measured by paw
      withdrawals to von Frey filaments and radiant heat stimuli were tested for 4
      weeks postinjury. Histological examination and volumetric analysis of spinal cord
      tissue were performed concomitantly. Spinally contused animals receiving NS-398
      demonstrated significantly (p < 0.05) reduced locomotor alteration and reductions
      in both fore- and hindlimb mechanical allodynia and thermal hyperalgesia when
      compared to vehicle controls. Histological examination of spinal segments at the
      lesion segment demonstrated reduced lesion extent and increased viable tissue
      when compared to vehicle controls. Prostaglandin E2 levels were significantly
      lowered in NS-398-treated but not vehicle-treated animals 12 h after injury.
      These results support the role of COX-2 in reducing pathological and behavioral
      deficits after spinal cord injury.

PMID- 11336443
TI  - Role of nitric oxide in the secondary expansion of a cortical brain lesion from
      cold injury.
AB  - We have investigated the role of nitric oxide (NO) as mediator of the secondary
      growth of a traumatic cortical necrosis. For this purpose, a highly standardized
      focal lesion of the brain was induced in 46 Sprague-Dawley rats by cold injury.
      Twenty-four hours later--the timepoint of maximal lesion spread--the animals were
      sacrificed and brains were removed for histomorphometry of the maximal necrosis
      area and volume. The animals were divided into five experimental groups. Group I
      received the NO donor L-arginine as i.v. bolus 10 min prior to trauma (300 mg/kg
      body weight; n = 10) and a second bolus of the same dosage intraperitoneally 1 h
      after trauma. Group II (n = 10)--serving as control of group I--was infused with
      an i.v. bolus of 1 mL/kg isotonic saline 10 min prior to and a subsequent bolus
      i.p. 1 h after trauma. Group III (n = 8) received 100 mg/kg b.w. of the inducible
      NOS (iNOS) inhibitor aminoguanidine (AG) 1 h before and 8 h after trauma by
      intraperitoneal route. Group IV was administered with the nitric oxide synthase
      (NOS) inhibitor N(G)-nitro-L-arginine (L-NNA; 100 mg/kg b.w., i.p.; n = 8); group
      V--the controls of group III and IV--was administered with isotonic saline (1
      mL/kg b.w. i.p.; n = 10) 1 h before and 8 h after trauma. In the control group
      with i.v./i.p. sham treatment (II), the focal lesion led to a cortical necrosis
      with a maximum area of 3.1 +/- 0.3 mm2 and a lesion volume of 5.7 +/- 0.5 mm3 at
      24 h after trauma. In animals with administration of L-arginine, the focal lesion
      had a maximum area of 3.1 +/- 0.3 mm2 and a volume of 5.3 +/- 0.5 mm3. Hence, the
      NO donor did not affect the secondary growth of necrosis. Animals with i.p. sham
      treatment (group V) had a maximal lesion area of 3.6 +/- 0.2 mm2 and lesion
      volume of 6.2 +/- 0.4 mm3. Administration of aminoguanidine afforded significant
      attenuation of the lesion growth. Accordingly, the maximal area of necrosis
      spread only to 2.8 +/- 0.2 mm2 with a volume of 4.5 +/- 0.5 mm3, respectively, at
      24 h after trauma (p < 0.01 vs group V). On the other hand, administration of L
      NNA did not influence the maximal lesion area (3.7 +/- 0.2 mm2) or lesion volume
      (6.5 +/- 0.5 mm3) evolving at 24 h after trauma. Thus, neither the enhancement of
      the formation of NO by L-arginine nor gross inhibition of the synthesis of NO by
      L-NNA did affect the secondary spread of the necrosis from a focal trauma. The
      marked attenuation of the posttraumatic necrosis growth by the iNOS inhibitor
      aminoguanidine strongly indicates an important role of iNOS product in this
      phenomenon. These findings, thus, demonstrate that the expansion of a primary
      necrotic focal lesion is a secondary process which can be therapeutically
      inhibited. Thereby, the growth of a focal tissue necrosis from trauma is clearly
      identified as a manifestation of secondary brain damage. This information is
      deemed important for the better understanding of the pathophysiology of traumatic
      brain injury and for the targeted development of specific treatment modalities.

PMID- 11336444
TI  - Expression of c-fos, heat shock protein 70, neurotrophins, and cyclooxygenase-2
      mRNA in response to focal cerebral ischemia/reperfusion in rats and their
      modification by magnesium sulfate.
AB  - The marginal area surrounding a region of ischemic brain tissue, designated as
      the penumbra, is of interest as a potential area for the rescue of neurons from
      cell death. Despite its clinical importance, relatively little is known about the
      molecular events leading to changes in brain cells in the penumbra following
      ischemia. In the first part of this study, we used in situ hybridization to
      investigate the temporal and spatial expression of c-fos, heat shock protein 70
      (HSP70), neurotrophins and inducible cyclooxygenase-2 (COX-2) in the rat brain
      following a 2-h occlusion of the middle cerebral artery (MCA) with reperfusion.
      In the penumbra and surrounding cortex, upregulation of c-fos, brain-derived
      neurotrophic factor (BDNF), and COX-2 mRNAs was observed, while expression of
      HSP70 mRNA was restricted to the penumbra. This spatial discrepancy of mRNA
      expression suggests that different mechanisms are involved in the regulation of c
      fos/BDNF/COX-2 and HSP70 expression. Intravenous infusion of magnesium sulfate
      (25 mg/kg) decreased both the infarct volume and upregulation of these mRNAs,
      suggesting its therapeutic potential.

PMID- 11336445
TI  - Zinc or copper deficiency-induced impaired inflammatory response to brain trauma
      may be caused by the concomitant metallothionein changes.
AB  - The role of zinc- and copper-deficient diets on the inflammatory response to
      traumatic brain injury (TBI) has been evaluated in adult rats. As expected, zinc
      deficiency decreased food intake and body weight gain, and the latter effect was
      higher than that observed in pair-fed rats. In noninjured brains, zinc deficiency
      only affected significantly lectin (increasing) and glial fibrillary acidic
      protein (GFAP) and Cu,Zn-superoxide dismutase (Cu,Zn-SOD) (decreasing)
      immunoreactivities (irs). In injured brains, a profound gliosis was observed in
      the area surrounding the lesion, along with severe damage to neurons as indicated
      by neuron specific enolase (NSE) ir, and the number of cells undergoing apoptosis
      (measured by TUNEL) was dramatically increased. Zinc deficiency significantly
      altered brain response to TBI, potentiating the microgliosis and reducing the
      astrogliosis, while increasing the number of apoptotic cells. Metallothioneins
      (MTs) are important zinc- and copper-binding proteins in the CNS, which could
      influence significantly the brain response to TBI because of their putative roles
      in metal homeostasis and antioxidant defenses. MT-I+II expression was
      dramatically increased by TBI, and this response was significantly blunted by
      zinc deficiency. The MT-III isoform was moderately increased by both TBI and zinc
      deficiency. TBI strongly increased oxidative stress levels, as demonstrated by
      malondialdehyde (MDA), protein tyrosine nitration (NITT), and nuclear factor
      kappaB (NF-kappaB) levels irs, all of which were potentiated by zinc deficiency.
      Further analysis revealed unbalanced expression of prooxidant and antioxidant
      proteins besides MT, since the levels of inducible nitric oxide synthase (iNOS)
      and Cu,Zn-SOD were increased and decreased, respectively, by zinc deficiency. All
      these effects were attributable to zinc deficiency, since pair-fed rats did not
      differ from normally fed rats. In general, copper deficiency caused a similar
      pattern of responses, albeit more moderate. Results obtained in mice with a null
      mutation for the MT-I+II isoforms strongly suggest that most of the effects
      observed in the rat brain after zinc and copper deficiencies are attributable to
      the concomitant changes in the MT expression.

PMID- 11336446
TI  - Subdural hematoma following traumatic brain injury causes a secondary decline in
      brain free magnesium concentration.
AB  - A number of studies have demonstrated that neurologic motor and cognitive
      deficits induced by traumatic brain injury (TBI) can be attenuated with
      administration of magnesium salts. However, many severe traumatic brain injuries
      have a significant hematoma that develops subsequent to the primary events, and
      it is unclear whether magnesium salts are effective in this situation. In the
      present study, an impact-acceleration rodent model of TBI was used to produce an
      injury that causes an extensive subdural hematoma in over 50% of injured animals.
      At 30 min after TBI, rats were randomly administered 250 micromoles/kg
      intravenous MgSO4 or equal volume saline before being monitored by magnetic
      resonance spectroscopy for 8 h to determine brain intracellular free magnesium
      concentration. Animals were then assessed for neurologic motor deficits over 1
      week using a rotarod device, followed by postmortem examination for presence of
      subdural hematoma. Animals with subdural hematoma treated with MgSO4 showed no
      improvement in motor outcome when compared to nontreated controls. Animals with
      no visible subdural hematoma demonstrated a significant improvement (p < 0.05 by
      ANOVA) in rotarod scores with MgSO4 treatment. Brain free magnesium concentration
      in the magnesium treated/hematoma group demonstrated a biphasic decline made up
      of an immediate initial decline, recovery of brain magnesium levels with MgSO4
      treatment, and then a significant second magnesium decline (p < 0.05). Such a
      secondary decline did not occur in the Mg treated/no hematoma animals. Our
      results suggest that development of a subdural hematoma following TBI results in
      a decline in brain magnesium, even after bolus administration of magnesium salts.
      Such effects of hematoma development will need to be considered in trials
      examining efficacy of magnesium salts as an intervention following TBI.

PMID- 11336447
TI  - Only early intervention with gamma-aminobutyric acid cell therapy is able to
      reverse neuropathic pain after partial nerve injury.
AB  - Pharmacological treatment for neuropathic pain, although often effective for
      brief periods, can result in intractable persistent pain with certain patients.
      Cell therapy for neuropathic pain is a newly developing technology useful for an
      examination of enhanced normal sensory function after nerve injury with the
      placement of cells near the spinal cord, and grafts of immortalized cells
      bioengineered to chronically supply the inhibitory neurotransmitter gamma
      aminobutyric acid (GABA) have been used to reverse the chronic pain behaviors.
      However, it is not known whether there is a therapeutic window for the use of
      intervention with cell therapy after partial nerve injury. To investigate whether
      neuropathic pain is sensitive to the timing of placement of cell grafts, neuronal
      cells bioengineered to synthesize GABA were transplanted in the lumbar
      subarachnoid space one to four weeks after unilateral chronic constriction injury
      (CCI) of the sciatic nerve and sensory behaviors were evaluated before and after
      CCI and transplants. Both thermal hyperalgesia and tactile allodynia were
      reversed when transplants were placed either one or two weeks after partial nerve
      injury, compared to maintenance of these behaviors with the injury alone.
      However, if GABA cells were placed any later than 2 weeks after nerve injury,
      such intervention was ineffective to reverse the thermal and tactile
      hypersensitivities induced by the injury. This suggests that altered spinal GABA
      levels may contribute to the early development of chronic neuropathic pain and
      that early intervention with cellular therapy to restore GABA may prevent the
      development of that pain.

PMID- 11336448
TI  - A new syndrome: heart defects, laryngeal anomalies, preaxial polydactyly, and
      colonic aganglionosis in sibs.
AB  - We present two siblings, one male and one female, who have heart defects,
      duplication of toes, airway anomalies, and aganglionosis. The brother also has a
      bilateral complete cleft lip and palate. His airway anomalies include short
      epiglottis and aryepiglottic folds, which are different from his sister who has a
      bifid epiglottis with a central epiglottic mass. Both siblings have had some
      developmental delay. This constellation of anomalies appears to be unique and may
      represent a new autosomal recessive disorder.

PMID- 11336449
TI  - Molecular analysis of an extended Palestinian family from Israel with
      monilethrix.
AB  - We describe the molecular analysis of a large three generation Palestinian family
      segregating for monilethrix. Previous reports have shown that mutations in type
      II hair cortex keratin genes, hHb1 and hHb6, are associated with monilethrix.
      Genetic linkage analysis performed on this family using markers flanking the hHb6
      gene exhibited strong evidence for linkage. Sequence analysis revealed a
      nucleotide substitution of G --> T at nucleotide 1230 resulting in a glutamic
      acid to aspartic acid amino acid substitution at codon 410, identical to that
      reported in a French family. The family in our study provides further evidence
      that mutations of the hHb6 gene are responsible for monilethrix.

PMID- 11336450
TI  - CPT coding revisions.

PMID- 11336451
TI  - I heartily praise the first issue of Genetics in Medicine for its immediate
      applicability to clinical genetic practice.

PMID- 11336453
TI  - BPMC drops hCG patent infringement lawsuit against Kaiser.

PMID- 11336454
TI  - The psychological impact of a negative BRCA1 test: a wolf in sheep's clothing?

PMID- 11336455
TI  - Human genome epidemiology: translating advances in human genetics into population
      based data for medicine and public health.

PMID- 11336457
TI  - Risk factors for trisomy 21: maternal cigarette smoking and oral contraceptive
      use in a population-based case-control study.
AB  - PURPOSE: We examined maternal smoking and oral contraceptive use as possible risk
      factors in the genesis of cases of trisomy 21 of maternal origin. This is the
      first epidemiological study to categorize cases of trisomy 21 by parent of origin
      and timing of the meiotic error before assessing possible risk factors. METHODS:
      We used chromosome 21-specific DNA markers to assign origin to each case.
      Structured interviews were employed to determine maternal smoking and oral
      contraceptive use around conception. RESULTS: The odds ratio (OR) for maternal
      smoking was significantly increased among younger mothers (OR = 2.98; 95% CI =
      1.01-8.87), but only in a particular subset of meiotically-derived cases. The
      combined use of cigarettes and oral contraceptives increased the risk further (OR
      = 7.62; 95% CI = 1.63-35.6); however, oral contraceptive use alone was not a
      significant risk factor. CONCLUSION: Our results indicate that categorizing cases
      of trisomy 21 by parent and timing of the meiotic error allows more precision in
      identifying risk factors and may shed light on mechanisms of meiotic
      nondisjunction.

PMID- 11336456
TI  - Psychological impact of receiving negative BRCA1 mutation test results in
      Ashkenazim.
AB  - PURPOSE: Most DNA test results for breast/ovarian cancer susceptibility are
      negative. Because negative test results might be interpreted incorrectly and may
      have serious psychological and behavioral implications, determining the
      psychological impact of such results is important. METHODS: A community-based
      sample of 289 Ashkenazim was tested for 185delAG. The 199 mutation-negatives
      provided data at baseline and follow-up. Increased risk participants included
      those who received negative test results but remained at increased risk because
      positive family and/or personal histories of breast or ovarian cancer made the
      results uninformative. Average risk meant those who tested negative and had
      negative family and personal histories of breast or ovarian cancer. Using a
      logistic regression analysis, both groups' psychological distress levels were
      compared at baseline and at 1 and 6 months after notification of DNA test
      results. RESULTS: A logistic regression analysis showed significant but small
      differences in cancer-specific distress after 6 months between increased and
      average risk participants (P < 0.006). Increased risk participants reported more
      distress than average risk. General distress declined among all participants
      after 1 month. Although baseline and follow-up differences in cancer-specific
      distress obtained by the increased and average risk participants were
      statistically significant, none of the absolute levels observed reflected
      especially high degrees of stress. CONCLUSIONS: Receipt of negative DNA test
      results does not have a deleterious psychological impact, whether results are
      informative or uninformative.

PMID- 11336458
TI  - Diagnosis of hemochromatosis in family members of probands: a comparison of
      phenotyping and HFE genotyping.
AB  - PURPOSE: We wanted to compare phenotyping and HFE genotyping for diagnosis of
      hemochromatosis in 150 family members of 61 probands. METHODS: Phenotypes were
      defined by persistent transferrin saturation elevation, iron overload, or both;
      genotypes were defined by HFE mutation analysis. RESULTS: Twenty-five family
      members were C282Y homozygotes; 23 of these (92%) had a hemochromatosis
      phenotype. Twenty-three family members had HFE genotype C282Y/H63D; eight of
      these (35%) had a hemochromatosis phenotype. Six of 102 (6%) family members who
      inherited other HFE genotypes had a hemochromatosis phenotype. CONCLUSION:
      Phenotyping and genotyping are complementary in diagnosing hemochromatosis among
      family members of probands.

PMID- 11336460
TI  - HER-2/neu gene amplification in stages I-IV breast cancer detected by fluorescent
      in situ hybridization.
AB  - PURPOSE: Approximately 25-30% of breast and ovarian carcinomas have amplification
      of the HER-2/neu oncogene. The aim of the present study was to focus on HER-2/neu
      gene amplification in different clinical stages of breast cancer in order to (1)
      determine if fluorescent in situ hybridization (FISH) can be used to detect HER
      2/neu gene amplification in different clinical stages of breast cancer, (2)
      establish whether HER-2/neu gene amplification characterizes a subset of breast
      cancer in each of these stages, and (3) determine whether a trend for correlation
      of amplification with the clinical stage of the disease can be detected using the
      FISH technology. METHODS: A total of 40 specimens of formalin-fixed, paraffin
      embedded breast cancer tissues were analyzed cytogenetically, in a blinded
      fashion, for HER-2/neu gene amplification using FISH and the Vysis LSI HER-2/neu
      Orange and CEP 17 Green DNA dual color probe. The criterion for "high
      amplification" was an amplification ratio of >4.0, that for "moderate
      amplification" a ratio between 2.1 and 4.0, and that for "low amplification" a
      ratio of 1.5-2.0. RESULTS: Using a cutoff point of > or =1.5, the overall
      frequency of HER-2/neu gene amplification among stage I tumors was 30% (3 out of
      10). Of these, one-third (1 out of 3) showed low amplification, one-third (1 out
      of 3) were moderately amplified, and one-third (1 out of 3) were highly
      amplified. The overall frequency of HER-2/neu gene amplification among stage II
      tumors was 0% (0 out of 10). The overall frequency of HER-2/neu gene
      amplification among stage III tumors was 10% (1 out of 10). The sole tumor found
      positive was classified as moderately amplified by our criteria. The overall
      frequency of HER-2/neu gene amplification among stage IV tumors was 50% (5 out of
      10). Four of the 5 tumors found positive were highly amplified. The overall
      frequency of gene amplification in the 40 cases studied was 22.5% (9 out of 40
      tumors studied). CONCLUSION: Although a linear correlation between HER-2/neu
      amplification and clinical stage cannot be established at this time, it is
      interesting to note that when stages I and II, and when stages III and IV are
      combined, respectively, the latter category has a higher amplification frequency
      than the former. Furthermore, stage IV has the highest frequency (5 out of 10) of
      HER-2/neu gene amplification than all three lower stages combined (4 out of 30).
      This is no doubt due to the high frequency of gene amplification observed in
      stage IV tumors, which, interestingly, also demonstrate high level amplification
      of HER-2/neu gene copy numbers. Although the biologic and clinical basis for gene
      amplification is not clear, given the observation that the most aggressive
      disease stage is associated with the highest frequency of gene amplification and
      the most high level amplification, further exploration of HER-2/neu as a
      prognostic marker of poor outcome using FISH is warranted.

PMID- 11336459
TI  - Detection of mosaicism in amniotic fluid cultures: a CYTO2000 collaborative
      study.
AB  - PURPOSE: To evaluate the assumptions on which the American College of Medical
      Genetics (ACMG) Standards and Guidelines for detecting mosaicism in amniotic
      fluid cultures are based. METHODS: Data from 653 cases of amniotic fluid
      mosaicism were collected from 26 laboratories. A chi-square goodness-of-fit test
      was used to compare the observed number of mosaic cases with the expected number
      based on binomial distribution theory. RESULTS: Comparison of observed data from
      the in situ colony cases with the expected distribution of cases detected based
      on the binomial distribution did not reveal a significant difference (P = 0.525).
      CONCLUSIONS: The empirical data fit the binomial distribution. Therefore,
      binomial theory can be used as an initial discussion point for determining
      whether ACMG Standards and Guidelines are adequate for detecting mosaicism.

PMID- 11336461
TI  - Adjuvant interferon in melanoma - a resurrection?

PMID- 11336462
TI  - Meta-analysis of single agents in the chemotherapy of NSCLC: what do we want to
      know?

PMID- 11336463
TI  - The role of mitomycin in the treatment of non-small cell lung cancer: a
      systematic review with meta-analysis of the literature.
AB  - In order to clarify the role of mitomycin (MMC) in the treatment of NSCLC, we
      performed a systematic review of the literature and qualitatively assessed the
      selected studies using the ELCWP and Chalmers scales. 5 trials (202 patients)
      assessed the activity of MMC as single-agent chemotherapy in NSCLC. The overall
      response rate was 25% (95% Cl 19-31). In 10 randomized phase III trials (1769
      patients), we studied the role of MMC in combination therapy. A meta-analysis,
      based on the available published data, failed to show any survival advantage of
      the MMC containing regimens (hazard ratio = 0.95; 95% Cl 0.83-1.10). Finally, 4
      eligible trials (139 patients) assessed the activity of MMC regimens as salvage
      therapy, 3 in combination with vindesine and one with cisplatin and vinblastine.
      The overall response rate for the MMC-vindesine regimen was 10.5% (95% Cl 1.7
      19.4). In conclusion, MMC is an active drug for NSCLC but does not improve
      survival when combined with other active drugs, particularly cisplatin. Its use
      for salvage therapy appears to be associated with marginal activity only.

PMID- 11336464
TI  - Clinical relevance of single item quality of life indicators in cancer clinical
      trials.
AB  - We investigated the hypothesis that global single-item quality-of-life indicators
      are less precise for specific treatment effects (discriminant validity) than
      multi-item scales but similarly efficient for overall treatment comparisons and
      changes over time (responsiveness) because they reflect the summation of the
      individual meaning and importance of various factors. Linear analogue self
      assessment (LASA) indicators for physical well-being, mood and coping were
      compared with the Hospital Anxiety and Depression Scale (HAD), the Mood Adjective
      Check List (MACL) and the emotional behaviour and social interaction scales of
      the Sickness Impact Profile (SIP) in 84 patients with early breast cancer
      receiving adjuvant therapy. Discriminant validity was investigated by multitrait
      multimethod correlation, responsiveness by standardized response mean (SRM).
      Discriminant validity of the indicators was present at baseline but less under
      treatment. Responsiveness was demonstrated by the expected pattern among
      treatments (P = 0.008). In patients without chemotherapy, the SRMs indicated
      moderate (0.5-0.8) to large (>0.8) improvements in physical well-being (0.70),
      coping (0.92), HAD anxiety (0.89) and depression (1.19), and MACL mental well
      being (0.68). In patients with chemotherapy for the first 3 months, small but
      clinically significant improvements (>).2) included mood (0.38), coping (0.41),
      HAD axiety (0.31) and MACL mental well-being (0.35). Patients with 6 months
      chemotherapy showed no changes. The indicators also reflected mood disorders
      (HAD) and marked psychosocial dysfunction (SIP) at baseline and under treatment
      according to pre-defined cut-off levels. Global indicators were confirmed to be
      efficient for evaluating treatments overall and changes over time. The lower
      reliability of single as opposed to multi-item scales affects primarily their
      discriminant validity. This is less decisive in large sample sizes.

PMID- 11336465
TI  - A weekly regimen of cisplatin, paclitaxel and topotecan with granulocyte-colony
      stimulating factor support for patients with extensive disease small cell lung
      cancer: a phase II study.
AB  - The present study was aimed at defining the antitumour activity of the cisplatin
      paclitaxel-topotecan (CPT) weekly administration with G-CSF support in chemo
      naive SCLC patients with extensive disease (ED-SCLC). Chemonaive ED-SCLC patients
      received cisplatin 40 mg/m(2), paclitaxel 85 mg/m(2), and topotecan 2.25
      mg/m(2)weekly, with G-CSF (5 microg/kg days 3-5) support, for a maximum of 12
      weeks. 37 patients were treated, for a total of 348 cycles delivered. 8 complete
      responses (22%) and 22 partial responses (59%) were recorded, giving an 81% [95%
      CI = 65-92%] ORR. At a 13-month (range, 4-26) median follow-up, median
      progression-free and overall survival were 8 months and 12.5 months, with 1-year
      and 2-year projected survivals of 55% and 21%, respectively. No toxic deaths
      occurred. Grade 4 neutropenia and thrombocytopenia occurred in 6 and 3 patients,
      respectively. Only one case of neutropenic sepsis was recorded, while
      haemorrhagic thrombocytopenia was never observed. Diarrhoea, paraesthesias and
      fatigue were the main nonhaematologic toxicities being severe in 6, 2 and 10
      patients, respectively. The weekly CPT combination with G-CSF support represents
      a well tolerated therapeutic approach in chemo-naive ED-SCLC patients. The
      activity rate seems at least similar to that achievable with the standard front
      line approaches.

PMID- 11336466
TI  - Chemotherapy for advanced breast cancer: what influences oncologists' decision
      making?
AB  - Chemotherapy is widely used in the management of patients with advanced breast
      cancer. However, a considerable proportion of patients experience toxic side
      effects without gaining benefit. This study aimed to elicit oncologists' views of
      the goals of chemotherapy for patients with advanced breast cancer and to elicit
      which factors are important in decisions to recommend chemotherapy to such
      patients. 30 oncologists underwent a semi-structured interview to examine their
      views of 5 goals of chemotherapy and of various disease, treatment and patient
      related factors that might influence decisions to offer treatment. The clinicians
      also made decisions regarding treatment in relation to a hypothetical patient
      scenario under varying clinical conditions. Relief of symptoms and improvement of
      activity were rated as the most valuable and achievable goals of treatment. The
      patient's performance status, frailty and their wishes regarding treatment were
      the most important patient-related factors in determining decision-making. The
      most important disease/treatment-related factors were pace of the disease,
      previous poor response to chemotherapy, co-existing symptoms and concurrent
      medical conditions. The hypothetical scenario revealed that co-existing medical
      conditions, adverse previous response, increased age and depression would
      decrease the likelihood of recommending chemotherapy, whereas key symptoms (e.g.
      breathlessness) and the patient's goals would increase the likelihood. The
      findings suggest that British oncologists primarily aim to improve patients'
      physical function, although subjective factors, such as a patient's desire for
      anti-cancer treatment and their future goals, also influence decisions to offer
      treatment.

PMID- 11336467
TI  - Combined paclitaxel and gemcitabine as first-line treatment in metastatic non
      small cell lung cancer: a multicentre phase II study.
AB  - The efficacy and toxicity of combined paclitaxel and gemcitabine was evaluated in
      54 chemotherapy-naive patients with metastatic non-small cell lung cancer
      (NSCLC). Gemcitabine i.v. 1000 mg/m(2)was administered on days 1 and 8 and
      paclitaxel 200 mg/m(2)as a continuous 3-hour infusion on day 1. Treatment was
      repeated every 21 days. Patients had a median age of 53 years. ECOG performance
      status was 0 or 1 in 48 patients. 41 patients (75.9%) had initial stage IV
      disease; histology was mainly adenocarcinoma (46.3%). 2 patients (4.3%) achieved
      a complete response and 15 (31.9%) achieved a partial response giving an overall
      response rate of 36.2% (95% CI: 22.4-49.9%); 19 patients (40.4%) had stable
      disease and 10 (21.3%) had progressive disease. The median survival time was 51
      weeks (95% CI: 46.5-59.3), with a 1-year survival probability of 0.48 (95% CI:
      0.34-0.63). Grade 3/4 neutropenia and febrile neutropenia occurred in 15.2% and
      2.2% of courses, respectively. Grade 3/4 thrombocytopenia was rare (1.8% of
      courses). Peripheral neurotoxicity developed in 25 patients (47.2%), mostly grade
      1/2. Arthalgia/myalgia was observed in 30 patients (56.6%), generally grade 1 or
      2. Grade 3 abnormal levels of serum glutamate pyruvate transaminase (SGPT) and
      serum glutamate oxaloacetate transaminase (SGOT) occurred in 5 patients (9.4%)
      and 1 patient (1.9%), respectively. Combined paclitaxel and gemcitabine is an
      active and well-tolerated regimen for the treatment of advanced NSCLC, and
      warrants further investigation in comparative, randomized trials.

PMID- 11336468
TI  - Seasonal variation in breast cancer diagnosis in Singapore.
AB  - This study investigates seasonality in the diagnosis of 3219 female breast
      carcinoma cases reported between 1995-8 in Singapore. There is little evidence of
      marked seasonal variation. Angular regression suggested that observed differences
      in peak diagnosis with respect to menopausal status, tumour size, ER and PR
      status may be chance.

PMID- 11336469
TI  - Breast cancer and NSAID use: a meta-analysis.
AB  - Recent epidemiological studies suggest that non-steroidal anti-inflammatory drugs
      (NSAIDs) reduce the risk of several cancers including breast cancer. This meta
      analysis examined the studies on NSAID use and breast cancer. The estimators of
      relative risk and associated variances, which have been adjusted for the greatest
      number of confounders, were abstracted and included in the meta-analysis.
      Combined estimators of relative risk (RR) were calculated using either fixed or
      random effect models. Meta-analyses were performed on 6 cohort studies (number of
      cases ranged from 14 to 2414) and 8 case-control studies (number of cases ranged
      from 252 to 5882). The combined estimate of relative risk was 0.82 (95%
      confidence interval [CI] = 0.75-0.89). The combined estimate for cohort studies
      was 0.78 (95% CI = 0.62-0.99) and was 0.87 (95% CI = 0.84-0.91) for case-control
      studies. The findings of this meta-analysis suggest that NSAID use may be
      associated with a small decrease in the risk of breast cancer. However, the
      available data are insufficient to estimate the dose-response effect for duration
      and frequency of use of any particular types of NSAID.

PMID- 11336470
TI  - Cancer risk in Swedish women: the relation to size at birth.
AB  - The relationship between fetal growth as indicated by weight and length at birth,
      and cancer risk in 1080 adult Swedish women was examined. Birth factors were
      retrieved from original midwife records for the years 1914, 1918, 1922 and 1930,
      and primary cancer cases were identified by matching with national and regional
      cancer registries through the year 1998. A positive and statistically significant
      increased risk for cancer was found with increasing birth weight or birth length
      for all site cancer and non-hormone related cancer, defined as all cancer sites
      excluding breast, uterus and ovary. Addition of factors suspected to influence
      cancer risk, maternal proteinuria, birth order, own parity and age at menarche,
      did not attenuate this relation. Previously only breast cancer has been reported
      to be related to size at birth in adult women and this is the first study to
      report that cancer sites other than the major hormone-related sites may be
      influenced by size at birth, as measured by either weight or length at birth;
      these findings warrant further investigation.

PMID- 11336471
TI  - Dietary factors and lung cancer risk in Japanese: with special reference to fish
      consumption and adenocarcinomas.
AB  - To investigate risk modification for lung cancer with diet in Japanese, we
      conducted a hospital-based case-control study and evaluated variation in
      influence with the histological type. We recruited 367 male and 240 female cases
      with adenocarcinomas, and 381 male and 57 female cases with squamous cell and
      small cell carcinomas. Controls comprised 2964 male and 1189 female cancer-free
      outpatients matched for sex and age with the cases. Odds ratios (ORs) and their
      95% confidence intervals (CIs) for lung cancer were calculated with adjustment
      for potential confounding factors, using an unconditional logistic model. We
      found decreased ORs for adenocarcinomas in both males (OR = 0.51, 95% CI 0.31
      0.84) and females (OR = 0.48, 95% CI 0.24-0.94) who consumed cooked/raw fish, but
      not dried/salted fish at the highest quartile frequency, compared with the
      lowest. Soybean curd consumption was associated with a decreased OR for female
      adenocarcinomas. Decreased ORs for squamous cell and small cell carcinomas were
      observed in males with frequent consumption of raw and green vegetables, fruit
      and milk, but consumption of carrot, pumpkin, egg and coffee was associated with
      increased ORs. This study suggests cooked/raw fish consumption lowers the risk of
      adenocarcinoma of the lung in Japanese.

PMID- 11336473
TI  - Childhood cancer in the south Asian population of England (1990-1992).
AB  - Cancer incidence in 1990-92 among English south Asian (residents with ethnic
      origins in India, Pakistan or Bangladesh) and non-south Asian children is
      compared. Standardized incidence ratios show significant overall excesses in
      south Asians (131), largely due to higher rates in south Asian boys, and specific
      excesses for leukaemia (141), lymphoid leukaemia (141), lymphoma (172) and
      hepatic tumours (375). Aetiological investigation is required.

PMID- 11336472
TI  - Cancer in the Gambia: 1988-97.
AB  - We describe the incidence of cancer in The Gambia over a 10-year period using
      data collected through the Gambian National Cancer Registry. Major problems
      involved with cancer registration in a developing country, specifically in Africa
      are discussed. The data accumulated show a low overall rate of cancer incidence
      compared to more developed parts of the world. The overall age standardized
      incidence rates (ASR) were 61.0 and 55.7 per 100 000 for males and females,
      respectively. In males, liver cancer was most frequent, comprising 58% of cases
      (ASR 35.7) followed by non-Hodgkin lymphoma, 5.4% (ASR 2.4), lung 4.0%, (ASR 2.8)
      and prostate 3.3% (ASR 2.5) cancers. The most frequent cancers in females were
      cervix uteri 34.0% (ASR 18.9), liver 19.4% (ASR 11.2), breast 9.2% (ASR 5.5) and
      ovary 3.2% (ASR 1.6). The data indicate that cancers of the liver and cervix are
      the most prevalent cancers, and are likely to be due to infectious agents. It is
      hoped that immunization of children under 1 year against hepatitis B will
      drastically reduce the incidence of liver cancer in The Gambia.

PMID- 11336474
TI  - HPV co-factors related to the development of cervical cancer: results from a
      population-based study in Costa Rica.
AB  - We examined factors associated with high-grade squamous intraepithelial lesions
      (HSIL) and cervical cancer among human papillomavirus (HPV)-infected women in a
      prevalent case-control study conducted within a population-based cohort of 10 077
      women in Costa Rica. We compared 146 women with HPV-positive HSIL or cancer
      (HSIL/CA) against 843 HPV-positive women without evidence of HSIL/CA. Subjects
      completed a risk factor questionnaire. We evaluated the associations between
      exposures and HSIL/CA among women positive for any HPV and restricted to those
      positive for high-risk HPV types. Risk of HSIL/CA increased with increasing
      number of live births (P(trend)= 0.04). Women who smoked 6+ cigarettes/day had a
      RR for HSIL/CA of 2.7 (95% CI = 1.1-6.7) compared to non-smokers. Current use of
      barrier contraceptives was associated with a reduction in risk of HSIL/CA (RR =
      0.39; 95% CI = 0.16-0.96). Sexual behaviour and a self-reported history of
      sexually transmitted diseases (STDs) other than HPV were not associated with
      HSIL/CA. Oral contraceptive use was associated with HSIL/CA among women with <3
      pregnancies. Effects were similar in analysis restricted to women positive for
      high-risk HPV types. Among women positive for high-risk HPV types, 44% of HSIL/CA
      could be attributed to multiparity (>/=3 pregnancies) and/or smoking. Among HPV
      positive women, multiparity and smoking are risk factors for HSIL/CA. Oral
      contraceptive use may be associated with HSIL/CA in subgroups of women.

PMID- 11336475
TI  - Assessment of the prognostic impact of the Epstein-Barr virus-encoded latent
      membrane protein-1 expression in Hodgkin's disease.
AB  - We have examined expression of the Epstein-Barr virus (EBV) latent membrane
      protein-1 (LMP1) in the malignant Hodgkin and Reed-Sternberg (HRS) cells of
      Hodgkin's disease (HD) and its impact on response to treatment and on survival.
      Paraffin tissue from 100 adult immunocompetent patients with HD were analysed
      using immunohistochemistry to identify LMP1 expression. According to the Rye
      classification, 8% of patients had lymphocyte predominance (LP) subtype, 48% had
      nodular sclerosis (NS) disease, 37% were of the mixed cellularity (MC) subtype
      and 7% were of the lymphocyte depletion (LD) subtype. During the five year follow
      up period 27 patients died and 74 patients achieved a complete remission.
      Patients with LD subtype were older (P = 0.03), less frequently achieved complete
      remission (P = 0.01), had shorter disease-free survival (P = 0.01) and overall
      survival (P = 0.002) compared with the other subtypes of HD. LMP1 expression was
      found in the tumour cells of 26% of cases of HD. LMP1 expression was less common
      in NS disease than in the other subtypes (P = 0.05), whereas an association
      between MC subtype and LMP1 expression was not found (P = 0.22). Using the log
      rank test there were no differences in overall survival or disease-free survival
      based on EBV status either when all patients were analysed or when LD and LP
      subtypes were excluded. However, the presence of EBV was associated with
      significantly longer disease-free survival in the subgroup of patients </= 30
      years old (P = 0.02) and in those patients </= 34 years old (P = 0.05). In
      contrast, there was a trend for shorter disease-free survival for EBV-positive
      patients in the subgroup > 35 years old, but this difference was not
      statistically significant (P = 0.11). A similar trend was observed in patients >
      50 years old. Analysis of the impact of LMP1 expression in patients who had
      different stage and B symptoms status showed that expression of EBV was
      associated with longer disease-free survival (P = 0.019) in early stage (1 + 2)
      patients without B symptoms. Significant differences in the other subgroups based
      on EBV status was not found. Factors adversely affecting the likelihood to
      achieve a complete remission were: absence of LMP1 expression (OR 6.4, 95% Cl
      1.07-38.5, P = 0.04), age (OR 1.68, 95%Cl 1.15-2.5, P = 0.007) and subtype of HD
      (OR 3.32, 95%Cl 1.11-9.94, P = 0.03). Age and subtype of HD had an independent
      impact on overall survival (P = 0.01). We conclude that expression of LMP1 in HRS
      cells has a favourable impact on prognosis for HD patients, but that this effect
      may be restricted to young adult patients and those with early stage disease.

PMID- 11336476
TI  - Transcriptional dysregulation of the p73L / p63 / p51 / p40 / KET gene in human
      squamous cell carcinomas: expression of Delta Np73L, a novel dominant-negative
      isoform, and loss of expression of the potential tumour suppressor p51.
AB  - We have recently identified a second p53 -related p73L gene, also referred to as
      p63 / p51 / p40 / KET gene, which encodes the 2 major isoforms p73L and p51
      resulting from different exon usage at their amino terminal regions. Although
      p73L and p51 are suspected to play oncogenic and tumour suppressive roles in
      mammalian cells, respectively, no evidence of linkage between the expression of
      these isoforms and human cancers has been reported so far. In this study, we
      first investigated the expression profile of p51 and p73L in various human tumour
      cell lines and found that a novel isoform, termed DeltaNp73L, was predominantly
      expressed in squamous cell carcinomas. The expression profile of
      DeltaNp73L/p73L/p51 in primary human skin cancer specimens showed that the
      expression of p51 was frequently lost (62%) but was detected in all normal skin
      samples. In p51-expressing skin cancers, DeltaNp73L expression was associated at
      a high frequency (75%) though it was not detected in normal skin tissues.
      Transient co-transfection data indicate the possibility that DeltaNp73L can
      inhibit p53-, and more preferentially, p51-mediated transactivation. These data
      suggest that the loss of expression of p51 and/or the expression of DeltaNp73L
      might contribute to the pathogenesis of human squamous cell carcinomas.

PMID- 11336477
TI  - Decreasing of p27(Kip1)and cyclin E protein levels is associated with progression
      from superficial into invasive bladder cancer.
AB  - The p27(Kip1)(p27) protein is a cyclin-dependent kinase inhibitor of the
      transition from G1 to S phase. It has been reported that decreased p27 protein
      level is a negative prognostic indicator in human tumours including bladder
      cancer. We studied the relationship between protein levels of p27, cyclin E and
      Ki-67 and clinicopathological features of 145 consecutive Japanese patients with
      transitional cell carcinoma of the bladder using immunohistochemical staining.
      Low protein levels of p27 were associated with low staining of cyclin E (P =
      0.0302), high Ki-67 index (P = 0.0306), poorly differentiated grade (P = 0.0006),
      muscle invasion (P = 0.0019) and lymph node metastsis (P = 0.0002). Low staining
      of cyclin E and high Ki-67 index correlated with poorly differentiated grade,
      muscle invasion and lymph node metastsis. Cyclin E protein levels was inversely
      related with Ki-67 index (P = 0.0002). Kaplan-Meier plots of survival rate in
      patients with low versus high p27 staining showed that low protein levels of p27
      were associated with a shortened disease-free and overall survival (P< 0.0001 and
      P< 0.0001, respectively). Similarly, low staining of cyclin E and high Ki-67
      index correlated with a shortened disease-free and overall survival. On
      multivariate analysis using Cox proportional hazards model, low protein levels of
      p27 and high Ki-67 index were independent predictors of shortened disease-free
      (P< 0.0001, P = 0.0031, respectively), and low protein levels of p27, low
      staining of cyclin E and high Ki-67 index of overall survival (P = 0.0017, P =
      0.0009, P = 0.0003, respectively). In superficial bladder tumours (Ta, T1; 86
      patients), significant correlations were observed between low p27 staining and
      high Ki-67 index and early recurrence (P = 0.0048, P = 0.0178, respectively).
      Among the recurrenced superficial tumours (35 patients), the tumours which
      remained at a low stage showed high protein levels of p27 and cyclin E, and the
      tumours which progressed to invasive disease showed a gradual decrease in p27 and
      cyclin E protein levels over time. Our findings suggest that decreased protein
      levels of p27 and cyclin E play a role in the progression of bladder cancer and
      to evaluate these protein levels may be useful in management of the diseases.

PMID- 11336478
TI  - Inhibition of breast cancer growth in vivo by antiangiogenesis gene therapy with
      adenovirus-mediated antisense-VEGF.
AB  - Increased expression of VEGF in several types of tumours has been shown to
      correlate with poor prognosis. We used a replication-deficient adenoviral vector
      containing antisense VEGF cDNA (Ad5CMV-alphaVEGF) to down-regulate VEGF
      expression and increase the efficiency of delivery of the antisense sequence in
      the human breast cancer cell line MDA231-MB. Transfection of these cells with
      Ad5CMV-alphaVEGF in vitro reduced secreted levels of VEGF protein without
      affecting cell growth. Moreover, injection of the Ad5CMV-alphaVEGF vector into
      intramammary xenografts of these cells established in nude mice inhibited tumour
      growth and reduced the amount of VEGF protein and the density of microvessels in
      those tumours relative to tumours treated with the control vector Ad5(dl312). Our
      results showed that antisense VEGF(165)cDNA was efficiently delivered in vivo via
      an adenoviral vector and that this treatment significantly inhibited the growth
      of established experimental breast tumours. The Ad5CMV-alphaVEGF vector may be
      useful in targeting the tumour vasculature in the treatment of breast cancer.

PMID- 11336479
TI  - Modulation of MUC1 mucin as an escape mechanism of breast cancer cells from
      autologous cytotoxic T-lymphocytes.
AB  - MUC1 mucin is known to serve as a target molecule in the killing of breast cancer
      cells by cytotoxic T-lymphocytes (CTLs). We searched for a possible mechanism
      allowing tumour cells to escape from autologous CTLs. When the killing of breast
      cancer cells by autologous lymphocytes was examined in 26 patients with breast
      cancer, significant tumour cell lysis was observed in 8 patients, whereas
      virtually no autologous tumour cell lysis was detected in as many as 18 patients.
      In the patients who showed negligible tumour cell lysis, the autologous tumour
      cells expressed MUC1-related antigenic epitopes much more weakly than the tumour
      cells in the patients who exhibited strong cytotoxicity (significant
      statistically at P< 0.0005-0.0045), suggesting that the unresponsiveness of
      cancer cells to CTLs observed in these patients was mainly due to loss of MUC1
      expression or modulation of its antigenicity. A breast cancer cell line, NZK-1,
      established from one of the cytotoxicity-negative patients, did not express MUC1
      and was resistant to killing by CTLs, while control breast cancer cell lines
      expressing MUC-1 were readily killed by CTLs. Transfection of NZK-1 cells with
      MUC1 cDNA induced significant lysis by autologous T-lymphocytes. These results
      supported the importance of MUC1 mucin in autologous anti-tumour immunity, but
      suggested that the major escape mechanism of tumour cells from autologous T
      lymphocytes is the loss and/or modulation of MUC1 antigenicity on tumour cells,
      which would limit the effectiveness of possible immunotherapy designed to target
      the MUC1 mucin.

PMID- 11336480
TI  - Kupffer cells of cirrhotic rat livers sensitize colon cancer cells to Fas
      mediated apoptosis.
AB  - Metastasis of colorectal carcinomas rarely occurs in cirrhotic livers. Our study
      investigated the influence of activated Kupffer cells from cirrhotic rat livers
      on hepatic colonization and FasR-mediated apoptosis of colon cancer cells. A rat
      colon cancer cell line, RCN-9, was used to inoculate rat livers. Treatment with
      conditioned media of Kupffer cells isolated from CCl(4)-induced cirrhotic rat
      livers (cirrhotic KCM) significantly reduced the incidence of hepatic
      colonization of RCN-9 cells. In vitro cytotoxicity of Kupffer cells and tumour
      infiltrating lymphocytes (TILs) on RCN-9 cells was evaluated using [(3)H]-release
      assay. RCN-9 cells were resistant to cytotoxicity mediated by cirrhotic Kupffer
      cells, but were sensitized to TIL-mediated killing after treatment with cirrhotic
      KCM. The specific killing induced by TILs was FasR-mediated, as it was inhibited
      by ZB4, an antagonistic anti-FasR antibody. In agreement, cirrhotic KCM increased
      recombinant Fas ligand-induced apoptosis of RCN-9 cells, and up-regulated FasR
      expression on RCN-9 cells as evaluated by RT-PCR and flow cytometry. These
      findings suggest that Kupffer cells in cirrhotic livers sensitize metastatic
      colon cancer cells to FasR-mediated apoptosis by up-regulating the receptors,
      which thus prepare them to be eliminated by infiltrating lymphocytes.

PMID- 11336481
TI  - The ratio of single- to double-strand DNA breaks and their absolute values
      determine cell death pathway.
AB  - Bleomycin is a cytotoxic antibiotic that generates DNA double-strand breaks (DSB)
      and DNA single-strand breaks (SSB). It is possible to introduce known quantities
      of bleomycin molecules into cells. Low amounts kill the cells by a slow process
      termed mitotic cell death, while high amounts produce a fast process that has
      been termed pseudoapoptosis. We previously showed that these types of cell death
      are a direct consequence of the DSB generated by bleomycin. Here, we use deglyco
      bleomycin, a bleomycin derivative lacking the carbohydrate moiety. Although this
      molecule performs the same nucleophilic attacks on DNA as bleomycin, we show that
      deglyco-bleomycin is at least 100 times less toxic to Chinese hamster fibroblasts
      than bleomycin. In fact, deglyco-bleomycin treatment results in apoptosis
      induction. In contrast, however, deglyco-bleomycin was found to generate almost
      exclusively SSB. Our results suggest that more than 150 000 SSB per cell are
      required to trigger apoptosis in Chinese hamster fibroblasts and that SSB are 300
      times less toxic than DSB. Taken together with previous studies on bleomycin, our
      data demonstrates that cells can die by apoptosis, mitotic cell death, or
      pseudoapoptosis, depending on the number of DNA breaks and on the ratio of SSB to
      DSB.

PMID- 11336482
TI  - Relationship of hypoxia to metastatic ability in rodent tumours.
AB  - The relationship between tumour oxygenation in vivo and metastatic potential was
      investigated in 2 rodent tumour models, KHT-C fibrosarcoma and SCC-VII squamous
      cell carcinoma. The oxygen status in these rodent tumours transplanted
      intramuscularly in syngeneic mice was measured using the Eppendorf
      pO(2)Histograph. The results indicate a considerable heterogeneity in oxygenation
      between individual tumours within each tumour cell line. At different tumour
      sizes, animals were killed and lung lobes were examined for macroscopic and
      microscopic lung metastases. In the KHT-C tumours, a significant increase in
      early pulmonary metastasis formation was observed in mice with hypoxic primary
      tumours. Hypoxic SCC-VII tumours did not give rise to enhanced lung metastasis
      formation despite oxygenation in a range similar to the KHT-C tumours. However,
      the overall metastasis incidence in the SCC-VII model was very low. The results
      obtained in the KHT-C model, which show that hypoxic tumours are more likely to
      metastasize, are in agreement with recent clinical data suggesting that a hypoxic
      environment might be implicated in metastatic ability of human tumours.

PMID- 11336484
TI  - Effect of cryopreservation on human articular chondrocyte viability,
      proliferation, and collagen expression.
AB  - Autotransplantation of human chondrocytes is an alternative therapeutic treatment
      for focal lesions of cartilage. During the process of isolation and culture of
      chondrocytes some problems that render the implantation of the cells unsuitable
      can occur. For security, some cells must be stored using cryopreservation. The
      objective of this study was to analyze the effect of cryopreservation on cellular
      viability, proliferation, and collagen expression of human chondrocytes. Human
      osteoarthritic cartilage (n = 23) was obtained and transferred to a sterile flask
      containing Dulbecco's modified Eagle's medium (DMEM) and antibiotics.
      Chondrocytes were isolated, cultured for 3-4 weeks, and frozen in DMEM containing
      10% human serum and 10% dimethyl sulfoxide by use of three different protocols. A
      cellular fraction was frozen directly to -80 degrees C (Protocol I). Another
      fraction was directly frozen to -80 degrees C and 24 h later introduced into
      liquid nitrogen (Protocol II). The last aliquot was frozen with controlled
      freezing using a freezing rate of -1 degrees C/min to a temperature of -40
      degrees C, 2 degrees C/min to -60 degrees C, and 5 degrees C/min to -150 degrees
      C (Protocol III). Cells were cryopreserved for 2 weeks. Cells from each
      cryopreservation method were then cultured for 7 days and cellular proliferation
      was evaluated by the counting of the total cells in each flask. Cryopreservation
      had a negative effect on chondrocyte survival and proliferation. The survival
      after cryopreservation with the three protocols was 70-75%. There was no
      significative difference between the methods used to cryopreserve (P = 0.4117).
      However, there was a significant difference among the donors (P = 0.0111).
      Cellular proliferation of chondrocytes was reduced by cryopreservation (P =
      0.024). The rate of proliferation of different groups was control samples 6.56,
      Protocol I 4.66, Protocol II 4.69, and Protocol III 5.58. Statistical analysis
      showed that the programmed protocol was the best method to preserve cellular
      functions. Chondrocytes were able to express collagen type II 1 week after
      cryopreservation. Cryopreservation modifies the survival and proliferation of
      chondrocytes. Of all protocols used to cryopreserve, the programmed protocol
      seems to be the best technique. Cryopreservation does not alter the collagen type
      II expression.

PMID- 11336485
TI  - Postthaw viability of precultured hepatocytes.
AB  - Hepatocytes are being studied for a wide variety of applications, including drug
      metabolism studies, gene therapy, and use in liver-assist devices for temporary
      liver support. The ability to cryopreserve isolated hepatocytes would permit the
      pooling of cells to reach the required therapeutic coordination of the cell
      supply with patient care regimes and the completion of safety and quality-control
      testing. The objective of this investigation was to develop a method of
      cryopreserving isolated hepatocytes that will retain high levels of function and
      facilitate the use of the cells in different applications. Freshly isolated
      hepatocytes were cultured in a spinner flask for different periods of time, up to
      48 h. The cells were cryopreserved by use of a range of solution concentrations
      and cooling rates. For fresh, nonfrozen hepatocytes precultured for 24 h prior to
      being plated on collagen, the albumin secretion rate was 0.88 +/- 0.62 mg/ml/h.
      When the cells were precultured for 24 h, frozen in a solution containing 10%
      Me2SO with a cooling rate of 1 degrees C/min, thawed, plated on collagen, and
      cultured, the albumin secretion rate was 0.21 +/- 0.24 microg/ml/h. In contrast,
      freshly isolated hepatocytes cryopreserved without preculture and cultured on
      collagen had an albumin secretion rate of 0.07 +/- 0.08 mg/ml/h. The influences
      of different solution compositions and cooling rates on postthaw function of
      precultured hepatocytes were also determined. These results indicate that the use
      of a preliminary culture step prior to cryopreservation can enhance the postthaw
      function of hepatocytes.

PMID- 11336486
TI  - Effect of amino acids on goat cauda epididymal sperm cryopreservation using a
      chemically defined model system.
AB  - Studies were carried out to analyze the cryoprotecting efficacy of several amino
      acids by use of a chemically defined synthetic medium (modified Ringer's
      solution) and goat cauda epididymal sperm as the model system. Motile goat cauda
      sperm dispersed in the synthetic medium were subjected to a freezing protocol in
      a computer-controlled bio-freezer, cooling 0.25 degrees C x min(-1) to 5 degrees
      C, 5 degrees C x min(-1) to -20 degrees C, and 20 degrees C x min(-1) to -100
      degrees C, prior to being plunged into liquid nitrogen. In the absence of amino
      acids, sperm cells completely lost their flagellar motility. Of all the amino
      acids tested, l-alanine showed maximal cryoprotection potential. l-Alanine at 135
      mM offered optimum cryoprotection potential: recovery of sperm forward motility
      and total motility were 14 +/- 2% and 19 +/- 2%, respectively. l-Glutamine, l
      proline, and glycine at optimum concentration (100-150 mM) cryopreserved approx.
      11-17% total motility of the sperm cells, whereas amino acids such as l-arginine,
      l-lysine, and l-histidine offered little cryoprotection (0-5%) to the cells.
      Increasing the amino acid concentration beyond the optimum level sharply
      decreased the recovery of the sperm motility, which therefore showed a biphasic
      cryoprotection profile. Addition of amino acids enhanced (approx. 7-10%) the
      cryoprotection efficacy of the well-known cryoprotectants glycerol and a
      combination of glycerol and dimethyl sulfoxide. The presence of glycerol caused a
      marked reduction (from 100-150 mM to 20-70 mM levels) in the optimal
      cryoprotective concentration of the amino acids. The combined cryoprotecting
      action of glycerol, dimethyl sulfoxide, and amino acids provided motility
      recovery as high as 52%. The observation that amino acids and dimethyl sulfoxide
      had an additive effect in augmenting the cryoprotecting potential of glycerol
      suggests that the mechanism of their action is different from that of glycerol.
      This cocktail of cryoprotectants may be useful for cryopreservation of semen of
      various species.

PMID- 11336487
TI  - Comparison of permeating and nonpermeating cryoprotectants for mouse sperm
      cryopreservation.
AB  - Mouse sperm has proven to be more difficult to cryopreserve than sperm of other
      mammalian species. Published reports show that only three cryoprotectant agents
      (CPAs), alone or combined, have been studied: glycerol and dimethyl sulfoxide
      (DMSO), as permeating agents, and raffinose, as a nonpermeating agent. To date,
      the most consistent results for mouse sperm cryopreservation have been achieved
      by use of raffinose/skim milk as cryoprotectant with rapid cooling at 20 degrees
      C per minute. In this study, we compared the cryoprotection provided by
      permeating (glycerol, formamide, propanediol, DMSO, adonitol) or nonpermeating
      (lactose, raffinose, sucrose, trehalose, d-mannitol) compounds for freezing mouse
      sperm. Different solutions were made using 3% skim milk solution as the buffer or
      extender in which all different cryoprotectant agents were dissolved at a
      concentration of 0.3 M, with a final osmolality of approx. 400 mOsm. Sperm
      samples from CB6F1 (hybrid) and C57BL/6J (inbred) mice collected directly into
      each CPA were frozen/thawed under identical conditions. After thawing and CPA
      elimination (centrifugation) raffinose (59%), trehalose (61%), and sucrose (61%)
      sustained the best motility (P = < 0.1) of the nonpermeating agents, whereas the
      best of the permeating agents was DMSO (42%). Membrane integrity was analyzed and
      showed that the simple exposure (prefreeze) to sugars was less harmful than the
      exposure to glycols. Coincidentally, sperm frozen in trehalose (41%), raffinose
      (40.5%), and sucrose (37.5%) were the samples less injured among all different
      postthawed CPA tested. The in vitro fertilization results demonstrated that
      hybrid mouse spermatozoa frozen with sugars (lactose 80%, raffinose 80%,
      trehalose 79% of two-cell embryos production) were more fertile than those frozen
      with glycols (glycerol 11%).

PMID- 11336488
TI  - Phosphorylation in coronary artery cold-induced contraction in the newborn lamb.
AB  - Myocardial dysfunction after hypothermic protection has been linked to various
      mechanisms. Coronary vasospasm in particular may be responsible for ischemic
      injury during reperfusion. Herein we hypothesized that coronary arteries (CA)
      sustain a cold-induced contraction during hypothermia mediated by a protein
      tyrosine kinase (PTK)-/protein tyrosine phosphatase (PTP)-dependent pathway.
      Isolated newborn lamb CA rings were studied in a tissue bath for isometric
      contraction during 2-h profound (17 degrees C) or ultra-profound (7 degrees C)
      hypothermia. In parallel, protein tyrosine phosphorylation was evaluated by use
      of the Western blot technique. Na-orthovanadate (SOV) and genestein (GEN) were
      used separately and in combination to evaluate the effect of PTK/PTP activation
      on CA contraction and tyrosine phosphorylation during cooling (17 or 7 degrees C)
      vs 37 degrees C. Cooling from 37 to 7 degrees C induced transient contraction at
      approximately 17 degrees C (29% KCl response), which was more prominent during
      rewarming to 37 degrees C (36% KCl). Cooling to 17 degrees C resulted in
      sustained contraction (7-10% KCl), which was reversible upon rewarming. Cold
      induced contraction was significantly enhanced by SOV (7- to 10-fold at 17
      degrees C; 2-fold at 7 degrees C) and abolished by GEN. Concurrently, tyrosine
      phosphorylation of 33-, 45-, and 104-kDa proteins increased during cooling (35
      100% at 17 degrees C; 46-66% at 7 degrees C). Tyrosine phosphorylation was
      similarly enhanced by SOV (1.7- to 2.3-fold at 17 degrees C; 2.9- to 3.9-fold at
      7 degrees C) and abolished by GEN in the presence or absence of SOV. These
      results support a prominent role for the PTK/PTP signal transduction pathway in
      the coronary artery cold-induced contraction. This information provides one
      possible biomolecular mechanism linked to ischemia/reperfusion pathophysiology of
      CA in neonatal hearts exposed to hypothermic myocardial protection.

PMID- 11336489
TI  - In vivo destruction of tumor tissue by cryoablation can induce inhibition of
      secondary tumor growth: an experimental study.
AB  - BACKGROUND: Cryoablation has been used successfully for the local treatment of
      several cancers. Besides local destruction, a systemic antitumor response has
      been postulated after cryoablation of tumor tissue. In this study we evaluate the
      possible systemic antitumor response induced by cryodestruction of tumor tissue
      in two mouse tumor models. METHODS: Mice received two subcutaneously placed tumor
      implants (thigh and flank) of the nonimmunogenic mouse colon tumor cell line,
      colon 26-B. After 7 days, the thigh implant was treated by cryoablation or
      excision and the effect on secondary tumor growth was determined by volume
      measurement of the nontreated flank tumor. Cytokine (IL-1alpha and TNF-alpha)
      levels in plasma were measured after treatment. Similar experiments were
      performed in nude mice using a human melanoma cell line (MV3). Moreover, in this
      model the effect of cryoablation on development of spontaneous lung metastases
      was evaluated. RESULTS: In the colon 26-B tumor model treatment of primary tumor
      implants by cryoablation resulted in a significant inhibition of secondary tumor
      growth compared to animals treated by surgical excision (P < 0.01). Six hours
      after treatment, plasma levels of IL-1alpha and TNF-alpha were higher after
      cryoablation than after excision (P < 0.01). Also in the nude mice model
      cryoablation resulted in inhibition of secondary tumor growth, though not
      significant. Mice treated by cryoablation showed significantly less lung
      metastases compared to those treated by excision (P = 0.03). CONCLUSIONS:
      Cryoablation of tumor tissue can result in inhibition of secondary and metastatic
      tumor growth. A cytokine response induced by cryoablation of tumor tissue may
      attribute to this feature.

PMID- 11336490
TI  - Investigation of the mechanism and the effect of cryoimmunology in the Copenhagen
      rat.
AB  - This study examined the potential for "cryoimmunology" to increase the
      destruction of the Dunning AT-1 prostate tumor after cryosurgery. Two possible
      mechanisms explaining the cryoimmunologic response were studied. The first was
      that an antitumor antibody is produced after cryosurgery. The second was that
      freezing induces an immunostimulatory signal that creates a T-cell response to
      the tumor. Six groups of animals (three experimental groups and three control
      groups) were treated once per week for 4 weeks with different therapies designed
      to investigate these mechanisms. Three types of immune response were measured:
      (1) the anti-AT-1 tumor immune titer (Ab response) by serum ELISA, (2) the effect
      on secondary tumor growth after challenge with live AT-1 cells (size and weight
      of the secondary tumor over time), and (3) the nature of the immunologic
      infiltrate into the secondary tumors by immunoperoxidase stain. ELISA showed that
      immune titers were present in the experimental groups after therapy, but the
      presence of an immune titer did not have a significant effect on tumor
      propagation. Histology showed the immunologic infiltrate was similar in all
      groups. These results showed that an immune response to AT-1 tumor was measurable
      by serum antibody, but it did not significantly limit secondary tumor growth or
      affect tumor histology. This suggests that the growth of AT-1 tumors is not
      inhibited by a cryoimmunological response. Thus, the effect of in vivo
      cryosurgery in the AT-1 tumor system would likely be limited to cellular and
      vascular changes.

PMID- 11336491
TI  - Effects of cooling and warming rates during vitrification on fertilization of in
      vitro-matured bovine oocytes.
AB  - The purpose of this study was to clarify the relationship of cooling rates (CR)
      and warming rates (WR) during vitrification with postwarming viability of in
      vitro-matured bovine oocytes. In Experiment 1, oocytes were vitrified in a
      solution containing 7.2 M ethylene glycol and 1.0 M sucrose by use of open-pulled
      glass capillaries with five different outer diameters and were warmed by
      placement of the capillaries into 0.25 M sucrose solution. The capillaries of
      2000-, 1400-, 1000-, 630-, and 440-mm diameters provided CR of 2000, 3000, 5000,
      8000, and 12,000 degrees C/min and WR of 5000, 8000, 17,000, 33,000, and 62,000
      degrees C/min, respectively. In oocytes vitrified in capillaries of 1400-mm
      diameter (CR, 3000 degrees C/min; WR, 8000 degrees C/min), the morphological
      survival rate (86% of vitrified), penetration rate (79% of inseminated), and
      normal fertilization rate (69% of penetrated) were higher or tended to be higher
      than those in the other vitrification groups. In Experiment 2, oocytes cooled at
      2000, 3000, or 12,000 degrees C/min were warmed at 8000 degrees C/min, and
      oocytes cooled at 3000 degrees C/min were warmed at 5000, 8000, or 33,000 degrees
      C/min. Among these CR-WR combinations, cooling of oocytes at 3000 degrees C/min
      regardless of the WR resulted in higher postwarming survival. These results
      indicate that survival of in vitro-matured bovine oocytes after vitrification and
      subsequent warming is improved by a slightly rapid cooling rate in open-pulled
      glass capillaries compared to that obtained in conventional straws.

PMID- 11336492
TI  - Effect of sequential cold shocks on survival and molting incidence in
      Panstrongylus megistus (Burmeister) (Hemiptera, Reduviidae).
AB  - The survival and molting incidence were studied in the insect, Panstrongylus
      megistus, following sequential cold shocks in which a milder shock at 0 or 5
      degrees C for 1 h preceded a more severe shock (0 degrees C, 12 h). The shocks
      were separated by intervals of 8, 18, 24, and 72 h at 28 degrees C. The survival
      rate after sequential shocks was identical to that of unshocked controls. Cold
      shock tolerance differed from heat-shock tolerance since the latter varied with
      the time between shocks and was much more transient. Sequential cold shocks
      produced a higher molting incidence when the first shock was given at 0 compared
      to 5 degrees C. This response was more rapid than that to sequential heat shocks.
      Cold-shock tolerance in P. megistus may involve heat-shock proteins, although
      other protective mechanisms may also occur concurrently. This is the first report
      of cold-shock tolerance in a blood-sucking hemipteran.

PMID- 11336493
TI  - Specification and morphogenesis of the zebrafish larval head skeleton.
AB  - Forward genetic analyses can reveal important developmental regulatory genes and
      how they function to pattern morphology. This is because a mutated gene can
      produce a novel, sometimes beautiful, phenotype that, like the normal phenotype,
      immediately seems worth understanding. Generally the loss-of-function mutant
      phenotype is simplified from the wild-type one, and often the nature of the
      pattern simplification allows one to deduce how the wild-type gene contributes to
      patterning the normal, more complex, morphology. This truism seems no less valid
      for the vertebrate head skeleton than for other and simpler cases of patterning
      in multicellular plants and animals. To show this, we review selected zebrafish
      craniofacial mutants. "Midline group" mutations, in genes functioning in one of
      at least three signal transduction pathways, lead to neurocranial pattern
      truncations that are primarily along the mediolateral axis. Mutation of
      lazarus/pbx4, encoding a hox gene partner, and mutation of valentino/kreisler, a
      hox gene regulator, produce anterior-posterior axis disruptions of pharyngeal
      cartilages. Dorsoventral axis patterning of the same cartilages is disrupted in
      sucker/endothelin-1 mutants. We infer that different signal transduction pathways
      pattern cartilage development along these three separate axes. Patterning of at
      least the anterior-posterior and dorsoventral axes have been broadly conserved,
      e.g., reduced Endothelin-1 signaling similarly perturbs cartilage specification
      in chick, mouse, and zebrafish. We hypothesize that Endothelin-1 also is an
      upstream organizer of the patterns of cellular interactions during cartilage
      morphogenesis.

PMID- 11336494
TI  - Intercellular communication via connexin43 gap junctions is required for ovarian
      folliculogenesis in the mouse.
AB  - The ovarian follicle in mammals is a functional syncytium, with the oocyte being
      coupled with the surrounding cumulus granulosa cells, and the cumulus cells being
      coupled with each other and with the mural granulosa cells, via gap junctions.
      The gap junctions coupling granulosa cells in mature follicles contain several
      different connexins (gap junction channel proteins), including connexins 32, 43,
      and 45. Connexin43 immunoreactivity can be detected from the onset of
      folliculogenesis just after birth and persists through ovulation. In order to
      assess the importance of connexin43 gap junctions for postnatal folliculogenesis,
      we grafted ovaries from late gestation mouse fetuses or newborn pups lacking
      connexin43 (Gja1(-)/Gja1(-)) into the kidney capsules of adult females and
      allowed them to develop for up to 3 weeks (this was necessitated by the neonatal
      lethality caused by the mutation). By the end of the graft period, tertiary
      (antral) follicles had developed in grafted normal (wild-type or heterozygote)
      ovaries. Most follicles in Gja1(-)/Gja1(-) ovaries, however, failed to become
      multilaminar, with the severity of the effect depending on strain background. Dye
      transfer experiments indicated that intercellular coupling between granulosa
      cells is reduced, but not abolished, in the absence of connexin43, consistent
      with the presence of additional connexins. These results suggest that coupling
      between granulosa cells mediated specifically by connexin43 channels is required
      for continued follicular growth. Measurements of oocyte diameters revealed that
      oocyte growth in mutant follicles is retarded, but not arrested, despite the
      arrest of folliculogenesis. The mutant follicles are morphologically abnormal:
      the zona pellucida is poorly developed, the cytoplasm of both granulosa cells and
      oocytes is vacuolated, and cortical granules are absent from the oocytes.
      Correspondingly, the mutant oocytes obtained from 3-week grafts failed to undergo
      meiotic maturation and could not be fertilized, although half of the wild-type
      oocytes from 3-week grafted ovaries could be fertilized. We conclude that
      connexin43-containing gap junction channels are required for expansion of the
      granulosa cell population during the early stages of follicular development and
      that failure of the granulosa cell layers to develop properly has severe
      consequences for the oocyte.

PMID- 11336495
TI  - Temporal and spatial effects of Sonic hedgehog signaling in chick eye
      morphogenesis.
AB  - Proper dorsal--ventral pattern formation of the optic cup is essential for
      vertebrate eye morphogenesis and retinotectal topographic mapping. Previous
      studies have suggested that midline tissue-derived Sonic hedgehog (Shh) molecules
      play critical roles in establishing the bilateral eye fields and in determining
      the proximal--distal axis of the eye primordium. Here, we have examined the
      temporal requirements for Shh during the optic vesicle to optic cup transition
      and after early optic cup formation in chick embryos. Both misexpressing Shh by
      virus and blocking Shh activity by antibodies resulted in disruption of ventral
      ocular tissues. Decreasing endogenous Shh signals unexpectedly revealed a sharp
      morphological boundary subdividing dorsal and ventral portions of the optic cup.
      In addition, Shh signals differentially influenced expression patterns of genes
      involved in ocular tissue specification (Pax6, Pax2, and Otx2) and dorsal-
      ventral patterning (cVax) within the ventral but not dorsal optic cup. Ectopic
      Shh suppressed expression of Bone Morphogenetic Protein 4 (BMP4) in the dorsal
      retina, whereas reducing endogenous Sonic hedgehog activity resulted in a ventral
      expansion of BMP4 territory. These results demonstrate that temporal requirements
      for Shh signals persist after the formation of the optic cup and suggest that the
      early vertebrate optic primordium may be subdivided into dorsal and ventral
      compartments. We propose a model in which ventrally derived Shh signals and
      dorsally restricted BMP4 signals act antagonistically to regulate the growth and
      specification of the optic primordium.

PMID- 11336496
TI  - Identification and characterization of Lbh, a novel conserved nuclear protein
      expressed during early limb and heart development.
AB  - We report the cloning, protein characterization, and expression of a novel
      vertebrate gene, termed Lbh (Limb-bud-and-heart), with a spatiotemporal
      expression pattern that marks embryologically significant domains in the
      developing limbs and heart. Lbh encodes a highly conserved nuclear protein, which
      in tissue culture cells possesses a transcriptional activator function. During
      limb development, expression of Lbh initiates in the ectoderm of the presumptive
      limb territory in the lateral body wall. As the limb buds appear, Lbh expression
      is restricted primarily to the distal ventral limb ectoderm and the apical
      ectodermal ridge, and overlaps in these ectodermal compartments with En1 and Fgf8
      expression. During heart formation, Lbh is expressed as early as Nkx2.5 and dHand
      in the bilateral heart primordia, with the highest levels in the anterior
      promyocardium. After heart tube fusion and looping, Lbh expression is confined to
      the ventricular myocardium, with the highest intensity in the right ventricle and
      atrioventricular canal, as well as in the sinus venosus. Based on the molecular
      characteristics and the domain-specific expression pattern, it is possible that
      Lbh functions in synergy with other genes known to be required for heart and limb
      development.

PMID- 11336497
TI  - Developmental expression of mouse Kruppel-like transcription factor KLF7 suggests
      a potential role in neurogenesis.
AB  - To identify potential functions for the Kruppel-like transcription factor KLF7,
      we have determined the spatiotemporal pattern of gene expression during
      embryogenesis and in the adult organism. We show that the profile of Klf7
      expression predominantly involves the central and peripheral nervous systems and
      is broadly identified by three separate phases. The first phase occurs early in
      embryogenesis with increasingly strong expression in the spinal cord, notably in
      motor neurons of the ventral horn, in dorsal root ganglia, and in sympathetic
      ganglia. The second robust phase of Klf7 expression is confined to the early
      postnatal cerebral cortex and is downregulated thereafter. The third phase is
      characterized by high and sustained expression in the adult cerebellum and dorsal
      root ganglia. Functionally, these three phases coincide with establishment of
      neuronal phenotype in embryonic spinal cord, with synaptogenesis and development
      of mature synaptic circuitry in the postnatal cerebral cortex, and with survival
      and/or maintenance of function of adult sensory neurons and cerebellar granule
      cells. Consistent with Klf7 expression in newly formed neuroblasts,
      overexpression of the gene in cultured fibroblasts and neuroblastoma cells
      repressed cyclin D1, activated p21, and led to G1 growth arrest. Based on these
      data, we argue for multiple potential functions for KLF7 in the developing and
      adult nervous system; they include participating in differentiation and
      maturation of several neuronal subtypes and in phenotypic maintenance of mature
      cerebellar granule cells and dorsal root ganglia.

PMID- 11336498
TI  - Mice deficient for spermatid perinuclear RNA-binding protein show neurologic,
      spermatogenic, and sperm morphological abnormalities.
AB  - Spermatid perinuclear RNA-binding protein (SPNR) is a microtubule-associated RNA
      binding protein that localizes to the manchette in developing spermatids. The
      Spnr mRNA is expressed at high levels in testis, ovary, and brain and is present
      in these tissues in multiple forms. We have generated a gene trap allele of the
      murine Spnr, named Spnr(+/GT). Spnr(GT/GT) mutants show a high rate of mortality,
      reduced weight, and an abnormal clutching reflex. In addition to minor anatomical
      abnormalities in the brain, males exhibit defects in spermatogenesis that include
      a thin seminiferous epithelium and disorganization of spermatogenesis. Most of
      the sperm from mutant males display defects in the flagellum and consequently
      show decreased motility and transport within the oviducts. Furthermore, sperm
      from mutant males achieve in vitro fertilization less frequently. Our findings
      suggest that SPNR plays an important role in normal spermatogenesis and sperm
      function. Thus, the Spnr(GT/GT) mutant male mouse provides a unique model for
      some human male infertility cases.

PMID- 11336499
TI  - Tracing transgene expression in living zebrafish embryos.
AB  - Ectopic expression by injection of plasmid DNA is rarely used in zebrafish
      embryos due to a low frequency of cells expressing a transgene of interest at
      detectable levels. Furthermore, the mosaic nature of ectopic expression by
      plasmid injection requires the direct detection of transgene-expressing cells. We
      have used the transcriptional activator Gal4-VP16 to amplify transgene expression
      in living zebrafish embryos. In comparison to conventional expression vectors,
      Gal4-VP16-amplified expression results in a significant higher number of cells
      which express a transgene at detectable levels. The Gal4-VP16-activator and the
      Gal4-VP16-dependent transgene can be placed on a single expression vector. Using
      tissue-specific regulatory elements, we show that expression of a Gal4-VP16
      dependent transgene can be reliably restricted to muscle, notochordal, or
      neuronal tissues. Furthermore, Gal4-VP16 can drive the expression of two or more
      transgenes from the same construct resulting in simultaneous coexpression of both
      genes in virtually all expressing cells. The reported expression system works
      effectively not only in zebrafish embryos but also in Xenopus embryos, chicken,
      mouse, and human cultured cells and is thus applicable to a broad variety of
      vertebrates. The high frequency of transgene expression together with the linked
      coexpression of more than one transgene opens the possibility of easily
      monitoring the behavior of individual transgene-expressing cells in real time by
      labeling them with the fluorescent reporter GFP. The combinatorial nature of the
      expression system greatly facilitates changing the tissue-specificity, the
      transgene expressed, or the cell compartment-specific GFP reporter, making it
      simpler to address a gene's function in different tissues as well as its cell
      biological consequences.

PMID- 11336500
TI  - Study of the murine allantois by allantoic explants.
AB  - The murine allantois will become the umbilical artery and vein of the
      chorioallantoic placenta. In previous studies, growth and differentiation of the
      allantois had been elucidated in whole embryos. In this study, the extent to
      which explanted allantoises grow and differentiate outside of the conceptus was
      investigated. The explant model was then used to elucidate cell and growth factor
      requirements in allantoic development. Early headfold-stage murine allantoises
      were explanted directly onto tissue culture plastic or suspended in test tubes.
      Explanted allantoises vascularized with distal-to-proximal polarity, they
      exhibited many of the same signaling factors used by the vitelline and
      cardiovascular systems, and they contained at least three cell types whose
      identity, gene expression profiles, topographical associations, and behavior
      resembled those of intact allantoises. DiI labeling further revealed that
      isolated allantoises grew and vascularized in the absence of significant cell
      mingling, thereby supporting a model of mesodermal differentiation in the
      allantois that is position- and possibly age-dependent. Manipulation of allantoic
      explants by varying growth media demonstrated that the allantoic endothelial cell
      lineage, like that of other embryonic vasculatures, is responsive to VEGF(164).
      Although VEGF(164) was required for both survival and proliferation of allantoic
      angioblasts, it was not sufficient to induce appropriate epithelialization of
      these cells. Rather, other VEGF isoforms and/or the outer sheath of mesothelium,
      whose maintenance did not appear to be dependent upon endothelium, may also play
      important roles. On the basis of these findings, we propose murine allantoic
      explants as a new tool for shedding light not only on allantoic development, but
      for elucidating universal mechanisms of blood vessel formation, including
      vascular supporting cells, either in the intact organism or in existing in vitro
      systems.

PMID- 11336501
TI  - Origins of inner ear sensory organs revealed by fate map and time-lapse analyses.
AB  - The inner ear develops from a simple ectodermal thickening called the otic
      placode into a labyrinth of chambers which house sensory organs that sense sound
      and are used to maintain balance. Although the morphology and function of the
      sensory organs are well characterized, their origins and lineage relationships
      are virtually unknown. In this study, we generated a fate map of Xenopus laevis
      inner ear at otic placode and otocyst stages to determine the developmental
      origins of the sensory organs. Our lineage analysis shows that all regions of the
      otic placode and otocyst can give rise to the sensory organs of the inner ear,
      though there were differences between labeled quadrants in the range of
      derivatives formed. A given region often gives rise to cells in multiple sensory
      organs, including cells that apparently dispersed from anterior to posterior
      poles and vice versa. These results suggest that a single sensory organ arises
      from cells in different parts of the placode or otocyst and that cell mixing
      plays a large role in ear development. Time-lapse videomicroscopy provides
      further evidence that cells from opposite regions of the inner ear mix during the
      development of the inner ear, and this mixing begins at placode stages. Lastly,
      bone morphogenetic protein 4 (BMP-4), a member of the transforming growth factor
      beta (TGF-beta) family, is expressed in all sensory organs of the frog inner ear,
      as it is in the developing chicken ear. Inner ear fate maps provide a context for
      interpreting gene expression patterns and embryological manipulations.

PMID- 11336502
TI  - Dominant Drop mutants are gain-of-function alleles of the muscle segment homeobox
      gene (msh) whose overexpression leads to the arrest of eye development.
AB  - Dominant Drop (Dr) mutations are nearly eyeless and have additional recessive
      phenotypes including lethality and patterning defects in eye and sensory bristles
      due to cis-regulatory lesions in the cell cycle regulator string (stg). Genetic
      analysis demonstrates that the dominant small eye phenotype is the result of
      separate gain-of-function mutations in the closely linked muscle segment homeobox
      (msh) gene, encoding a homeodomain transcription factor required for patterning
      of muscle and nervous system. Reversion of the Dr(Mio) allele was coincident with
      the generation of lethal loss-of-function mutations in msh in cis, suggesting
      that the dominant eye phenotype is the result of ectopic expression. Molecular
      genetic analysis revealed that two dominant Dr alleles contain lesions upstream
      of the msh transcription start site. In the Dr(Mio) mutant, a 3S18
      retrotransposon insertion is the target of second-site mutations (P-element
      insertions or deletions) which suppress the dominant eye phenotype following
      reversion. The pattern of 3S18 expression and the absence of msh in eye imaginal
      discs suggest that transcriptional activation of the msh promoter accounts for
      ectopic expression. Dr dominant mutations arrest eye development by blocking the
      progression of the morphogenetic furrow leading to photoreceptor cell loss via
      apoptosis. Gal4-mediated ubiquitous expression of msh in third-instar larvae was
      sufficient to arrest the morphogenetic furrow in the eye imaginal disc and
      resulted in lethality prior to eclosion. Dominant mutations in the human msx2
      gene, one of the vertebrate homologs of msh, are associated with
      craniosynostosis, a disease affecting cranial development. The Dr mutations are
      the first example of gain-of-function mutations in the msh/msx gene family
      identified in a genetically tractible model organism and may serve as a useful
      tool to identify additional genes that regulate this class of homeodomain
      proteins.

PMID- 11336503
TI  - FGF signaling in chick lens development.
AB  - The prevailing concept has been that an FGF induces epithelial-to-fiber
      differentiation in the mammalian lens, whereas chick lens cells are unresponsive
      to FGF and are instead induced to differentiate by IGF/insulin-type factors. We
      show here that when treated for periods in excess of those used in previous
      investigations (>5 h), purified recombinant FGFs stimulate proliferation of
      primary cultures of embryonic chick lens epithelial cells and (at higher
      concentrations) expression of the fiber differentiation markers delta-crystallin
      and CP49. Surprisingly, upregulation of proliferation and delta-crystallin
      synthesis by FGF does not require activation of ERK kinases. ERK function is,
      however, essential for stimulation of delta-crystallin expression in response to
      insulin or IGF-1. Vitreous humor, the presumptive source of differentiation
      promoting activity in vivo, contains a factor capable of diffusing out of the
      vitreous body and inducing delta-crystallin and CP49 expression in chick lens
      cultures. This factor binds heparin with high affinity and increases delta
      crystallin expression in an ERK-insensitive manner, properties consistent with an
      FGF but not insulin or IGF. Our findings indicate that differentiation in the
      chick lens is likely to be mediated by an FGF and provide the first insights into
      the role of the ERK pathway in growth factor-induced signal transduction in the
      lens.

PMID- 11336505
TI  - Pannier is a transcriptional target and partner of Tinman during Drosophila
      cardiogenesis.
AB  - During Drosophila embryogenesis, the homeobox gene tinman is expressed in the
      dorsal mesoderm where it functions in the specification of precursor cells of the
      heart, visceral, and dorsal body wall muscles. The GATA factor gene pannier is
      similarly expressed in the dorsal-most part of the mesoderm where it is required
      for the formation of the cardial cell lineage. Despite these overlapping
      expression and functional properties, potential genetic and molecular
      interactions between the two genes remain largely unexplored. Here, we show that
      pannier is a direct transcriptional target of Tinman in the heart-forming region.
      The resulting coexpression of the two factors allows them to function
      combinatorially in the regulation of cardiac gene expression, and a physical
      interaction of the proteins has been demonstrated in cultured cells. We also
      define functional domains of Tinman and Pannier that are required for their
      synergistic activation of the D-mef2 differentiation gene in vivo. Together,
      these results provide important insights into the genetic mechanisms controlling
      heart formation in the Drosophila model system.

PMID- 11336504
TI  - Pod-2, along with pod-1, defines a new class of genes required for polarity in
      the early Caenorhabditis elegans embryo.
AB  - The asymmetric division of the one-cell Caenorhabditis elegans zygote gives rise
      to two cells of different size and fate, thereby establishing the animal's
      anterior--posterior (a-p) axis. Through genetics, a number of genes required for
      this polarity have been characterized, but many components remain unidentified.
      Recently, our laboratory discovered a mutation in the pod-1 gene (for polarity
      and osmotic defective) that uniquely perturbed polarity and osmotic protection.
      Here, we describe a new C. elegans polarity gene identified during screens for
      conditional embryonic lethals. Embryos in which this gene has been mutated show a
      loss of physical and developmental asymmetries in the one-cell embryo, including
      the mislocalization of PAR and POD-1 proteins required for early polarity.
      Furthermore, mutant embryos are osmotically sensitive, allowing us to designate
      this gene pod-2. Thus, pod-2, along with pod-1, defines a new class of C. elegans
      polarity genes. Genetic analyses indicate that pod-2 functions in the same
      pathway as pod-1. Temperature-shift studies indicate that pod-2 is required
      during oogenesis, indicating that aspects of embryonic polarization may precede
      fertilization. pod-2 mutant embryos also exhibit a unique germline inheritance
      defect in which germline identity localizes to the wrong spot in the one-cell
      embryo and is therefore inherited by the wrong cell at the four-cell stage. Our
      data suggest that pod-2 may be required to properly position an a-p polarity cue.

PMID- 11336506
TI  - Cell death and neuronal replacement during formation of the avian ciliary
      ganglion.
AB  - Programmed cell death is a prominent feature of embryonic development and is
      essential in matching the number of neurons to the target tissues that are
      innervated. Although a decrease in neuronal number which coincides with
      peripheral synaptogenesis has been well documented in the avian ciliary ganglion,
      it has not been clear whether cell death also occurs earlier. We observed TUNEL
      positive neurons as early as stage 24, with a large peak at stage 29. This cell
      death at stage 29 was followed by a statistically significant (P < 0.0001)
      decrease in total neuron number at stage 31. The total number of neurons was
      recovered by stage 33/34. This suggested that dying neurons were replaced by new
      neurons. This replacement process did not involve proliferation because
      bromodeoxyuridine applied at stages 29 and 31 was unable to label neurons
      harvested at stage 33/34. The peak of cell death at stage 29 was increased 2.3
      fold by removal of the optic vesicle and was reduced by 50% when chCNTF was
      overexpressed. Taken together, these results suggest that the regulation of
      neuron number in the ciliary ganglion is a dynamic process involving both cell
      death and neural replacement from postmitotic precursors prior to differentiation
      and innervation of target tissues.

PMID- 11336507
TI  - Epithelial development and differentiation in the mammary gland is not dependent
      on alpha 3 or alpha 6 integrin subunits.
AB  - In the mammary gland, both laminin and integrins have been shown to be required
      for normal ductal morphogenesis during development in vivo, and for functional
      differentiation in culture models. Major integrin receptors for laminins in the
      mammary gland are alpha 3 beta 1, alpha 6 beta 1, and alpha 6 beta 4. However,
      the specific subunits that contribute to laminin-mediated mammary cell function
      and development have not been identified. In this study, we use a genetic
      approach to test the hypothesis that laminin-binding integrins are required for
      the function of the mammary gland in vivo. Rudiments of embryonic mammary gland
      were shown to develop in the absence of these integrin subunits. Postnatal
      development of the mammary gland was studied in integrin null tissue that had
      been transplanted into the mammary fat pads of syngeneic hosts. In mammary
      epithelium lacking alpha 6 integrin, the beta 4 subunit was not apparent and
      hemidesmosome formation was only rudimentary. However, despite this deficiency,
      normal ductal morphogenesis and branching of the mammary gland occurred and
      myoepithelial cells were distributed normally with respect to luminal cells.
      Mammary alveoli devoid of alpha 3 or alpha 6 integrin formed in pregnancy and
      were histologically and functionally identical to those in wild-type mammary
      gland. The tissue underwent full morphological differentiation, and the
      epithelial cells retained the ability to synthesize beta-casein. This work
      demonstrates that mammary tissue genetically lacking major laminin-binding
      integrin receptors is still able to develop and function.

PMID- 11336508
TI  - Differences in Krox20-dependent regulation of Hoxa2 and Hoxb2 during hindbrain
      development.
AB  - During hindbrain development, segmental regulation of the paralogous Hoxa2 and
      Hoxb2 genes in rhombomeres (r) 3 and 5 involves Krox20-dependent enhancers that
      have been conserved during the duplication of the vertebrate Hox clusters from a
      common ancestor. Examining these evolutionarily related control regions could
      provide important insight into the degree to which the basic Krox20-dependent
      mechanisms, cis-regulatory components, and their organization have been
      conserved. Toward this goal we have performed a detailed functional analysis of a
      mouse Hoxa2 enhancer capable of directing reporter expression in r3 and r5. The
      combined activities of five separate cis-regions, in addition to the conserved
      Krox20 binding sites, are involved in mediating enhancer function. A CTTT (BoxA)
      motif adjacent to the Krox20 binding sites is important for r3/r5 activity. The
      BoxA motif is similar to one (Box1) found in the Hoxb2 enhancer and indicates
      that the close proximity of these Box motifs to Krox20 sites is a common feature
      of Krox20 targets in vivo. Two other rhombomeric elements (RE1 and RE3) are
      essential for r3/r5 activity and share common TCT motifs, indicating that they
      interact with a similar cofactor(s). TCT motifs are also found in the Hoxb2
      enhancer, suggesting that they may be another common feature of Krox20-dependent
      control regions. The two remaining Hoxa2 cis-elements, RE2 and RE4, are not
      conserved in the Hoxb2 enhancer and define differences in some of components that
      can contribute to the Krox20-dependent activities of these enhancers.
      Furthermore, analysis of regulatory activities of these enhancers in a Krox20
      mutant background has uncovered differences in their degree of dependence upon
      Krox20 for segmental expression. Together, this work has revealed a surprising
      degree of complexity in the number of cis-elements and regulatory components that
      contribute to segmental expression mediated by Krox20 and sheds light on the
      diversity and evolution of Krox20 target sites and Hox regulatory elements in
      vertebrates.

PMID- 11336509
TI  - Early morphogenesis of the Caenorhabditis elegans pharynx.
AB  - We investigated the cellular behaviors that accompany the early stages of
      pharyngeal morphogenesis in Caenorhabditis elegans. The embryonic pharynx
      develops from a ball of cells into a linear tube connected anteriorly to the
      buccal cavity and posteriorly to the midgut. By using GFP reporters localized to
      discrete subcellular regions, we show that pharyngeal morphogenesis can be
      divided into three stages: (1) lengthening of the nascent pharyngeal lumen by
      reorientation of apicobasal polarity of anterior pharyngeal cells
      ("Reorientation"), (2) formation of an epithelium by the buccal cavity cells,
      which mechanically couples the buccal cavity to the pharynx and anterior
      epidermis ("Epithelialization"), and (3) a concomitant movement of the pharynx
      anteriorly and the epidermis of the mouth posteriorly to bring the pharynx,
      buccal cavity, and mouth into close apposition ("Contraction"). Several models
      can account for these cellular behaviors, and we distinguish between them by
      physically or genetically ablating cells within the digestive tract. These
      studies provide the first description of how the pharynx primordium develops into
      an epithelial tube, and reveal that pharyngeal morphogenesis resembles aspects of
      mammalian kidney tubulogenesis.

PMID- 11336511
TI  - Local sonic hedgehog signaling regulates oligodendrocyte precursor appearance in
      multiple ventricular zone domains in the chick metencephalon.
AB  - In the chick metencephalon, oligodendrocyte precursors arise in distinct domains
      of the ventricular zone. During development, the earliest oligodendrocyte
      precursors appear in the metencephalic ventral ventricular zone adjacent to the
      midline, consistent with their location in the spinal cord. In contrast to spinal
      cord, however, distinct domains in the lateral and dorsal metencephalic
      ventricular zone subsequently generate oligodendrocyte precursors. All
      oligodendrogenic domains of the metencephalon appear in close apposition to
      regions that transiently express sonic hedgehog (Shh). Inhibition studies
      demonstrate a functional requirement for Shh signaling in the early appearance of
      metencephalic oligodendrocyte precursors, while in vitro studies suggest a dose
      dependent increase in the number of oligodendrocyte precursors in response to
      Shh. In purified cultures of oligodendrocyte precursors, Shh promotes cell
      survival and proliferation, suggesting that Shh can act directly on these cells.
      These data suggest that Shh may be responsible for the localized appearance of
      oligodendrocyte precursors throughout the CNS, irrespective of the dorso-ventral
      neural axis.

PMID- 11336510
TI  - Xebf3 is a regulator of neuronal differentiation during primary neurogenesis in
      Xenopus.
AB  - During primary neurogenesis in Xenopus, a cascade of helix--loop--helix (HLH)
      transcription factors regulates neuronal determination and differentiation. While
      XNeuroD functions at a late step in this cascade to regulate neuronal
      differentiation, the factors that carry out terminal differentiation are still
      unknown. We have isolated a new Xenopus member of the Ebf/Olf-1 family of HLH
      transcription factors, Xebf3, and provide evidence that, during primary
      neurogenesis, it regulates neuronal differentiation downstream of XNeuroD. In
      developing Xenopus embryos, Xebf3 is turned on in the three stripes of primary
      neurons at stage 15.5, after XNeuroD. In vitro, XEBF3 binds the EBF/OLF-1 binding
      site and functions as a transcriptional activator. When overexpressed, Xebf3 is
      able to induce ectopic neurons at neural plate stages and directly convert
      ectodermal cells into neurons in animal cap explants. Expression of Xebf3 can be
      activated by XNeuroD both in whole embryos and in animal caps, indicating that
      this new HLH factor might be regulated by XNeuroD. Furthermore, in animal caps,
      XNeuroD can activate Xebf3 in the absence of protein synthesis, suggesting that,
      in vitro, this regulation is direct. Similar to XNeuroD, but unlike Xebf2/Xcoe2,
      Xebf3 expression and function are insensitive to Delta/Notch-mediated lateral
      inhibition. In summary, we conclude that Xebf3 functions downstream of XNeuroD
      and is a regulator of neuronal differentiation in Xenopus.

PMID- 11336512
TI  - Human cytotrophoblast expression of the von Hippel-Lindau protein is
      downregulated during uterine invasion in situ and upregulated by hypoxia in
      vitro.
AB  - The von Hippel-Lindau tumor-suppressor protein (pVHL) regulates the stability of
      HIF1 alpha and HIF2 alpha and thus is pivotal in cellular responses to changes in
      oxygen tension. Paradoxically, human cytotrophoblasts proliferate under hypoxic
      conditions comparable to those measured in the early gestation placenta (2%
      O(2)), but differentiate into tumorlike invasive cells under well-oxygenated
      conditions such as those found in the uterus. We sought to explain this
      phenomenon in terms of pVHL expression. In situ, pVHL immunolocalized to villous
      cytotrophoblast stem cells, and expression was enhanced at sites of cell column
      initiation; in both of these relatively hypoxic locations, cytoplasmic staining
      for HIF2 alpha was also detected. As cytotrophoblasts attached to and invaded the
      uterus, which results in their increased exposure to oxygen, pVHL staining was
      abruptly downregulated concordant with localization of HIF2 alpha to the nucleus.
      In vitro, hypoxia (2% O(2)) upregulated cytotrophoblast pVHL expression together
      with HIF2 alpha, which localized to the cytoplasm; culture under well-oxygenated
      conditions greatly reduced levels of both molecules. These results, together with
      the placental defects previously observed in VHL(-/-) mice, suggest that pVHL is
      a component of the mechanism that transduces local differences in oxygen tension
      at the maternal-fetal interface to changes in the biological behavior of
      cytotrophoblasts. Furthermore, these data provide the first example of oxygen
      dependent changes in pVHL abundance.

PMID- 11336513
TI  - Critical Evaluation of the Prediction of the Dissociation Energy and the Energy
      Spectrum of the Ground State of KRb by the Reduced Potential Curve Method.
AB  - The estimates of the value of the dissociation energy and the energy spectrum of
      the KRb molecule made previously (O. Bludsky, M. Ju&rbreve;ek, V. Spirko, B. A.
      Brandt, and F. Jen&cbreve;, 1995, J. Mol. Spectrosc. 169, 555-582) are compared
      with the new experimental data (C. Amiot and J. Verges, 2000, J. Chem. Phys. 112,
      7068-7074) and the efficacy of the reduced potential curve (RPC) method is
      demonstrated. Copyright 2001 Academic Press. 

PMID- 11336514
TI  - Further Investigations of the ClO Rotational Spectrum.
AB  - Pure rotational transitions of the chlorine monoxide radical have been observed
      up to v=2 in the X(1) (2)Pi(3/2) and X(2) (2)Pi(1/2) states and transitions of
      the (35)Cl(18)O isotopomer have been observed in natural abundance. Additionally,
      rotational transitions for levels up to J'=115/2 have been measured in the far
      infrared. These data have been merged with the existing microwave, submillimeter,
      and high-resolution infrared transition frequencies and fit simultaneously with a
      set of isotopically independent parameters. Isotopic substitution of both the Cl
      and O atoms has enabled the first determination of the electron spin-rotation
      constant gamma=-296.0(43) MHz as well as the Born-Oppenheimer corrections to the
      rotational constants. Copyright 2001 Academic Press. 

PMID- 11336515
TI  - Submillimeter-Wave Spectra of the SF Radical.
AB  - Pure rotational transitions of the SF radical in the ground electronic state,
      (2)Pi, have been measured in the millimeter- and submillimeter-wave region using
      a spectrometer equipped with backward wave oscillators as radiation sources. The
      radical was generated by a dc discharge in a gas mixture of SF(6) and He. Forty
      four lines have been measured in the frequency range from 248 to 845 GHz, for J
      values up to 25.5. The accuracy in line position measurement is typically 20-100
      kHz, depending on the Doppler broadening. The present data were analyzed by a
      least-squares-fit procedure using an effective Hamiltonian for (2)Pi states,
      together with the transition frequencies in the microwave region available in the
      literature. The molecular constants have been revised with improved accuracy.
      Copyright 2001 Academic Press. 

PMID- 11336516
TI  - Mass Derivatives of Molecular Parameters and Distortions in r((2))(m) Structures.
AB  - Expressions are derived for the derivatives of various molecular vibration
      rotation parameters with respect to atomic masses. These are applied to determine
      an expression for the mass derivatives of the zero-point moments of inertia, and
      hence the theoretical substitution coordinates. It is then possible to calculate
      the distortions in structures determined by means of the r((2))(m) method. The
      latter agree well with the distortions found in r((2))(m) fits of synthetic data.
      Copyright 2001 Academic Press. 

PMID- 11336517
TI  - The Electronic Spectrum of Germanium Monosulfide: Rotational Structure in the
      A(1)Pi-X(1)Sigma(+) Transition in (70)GeS.
AB  - The emission spectrum of the specific isotopomer (70)GeS was excited in a
      microwave (2450-MHz) discharge and the A(1)Pi-X(1)Sigma(+) transition (270-430
      nm) was photographed under high resolution on a 10.6-m Ebert grating
      spectrograph. The rotational analysis of 43 bands led to the determination of
      accurate vibrational and rotational constants. Making use of these constants, the
      potential energy curves for the A(1)Pi and X(1)Sigma(+) states were generated by
      the RKR method and Franck-Condon factors and r-centroids were computed for the
      bands analyzed. The present extensive high-resolution study has revealed only a
      few localized perturbations in the A(1)Pi (v'=4, 5, 9) vibronic states, which
      contrasts with the situation in the isovalent molecules such as GeO, SiS, and
      SiSe. Copyright 2001 Academic Press. 

PMID- 11336518
TI  - Rovibrational Study of the CH(2) Wagging Fundamental of Monofluoroacetonitrile.
AB  - The vapor-phase infrared spectrum of monofluoroacetonitrile (CH(2)FCN) has been
      recorded at high resolution in the nu(4) band region (1363-1398 cm(-1)) using a
      tunable diode laser spectrometer. A detailed assignment of the rotational
      structure of the expected a-/b-hybrid band has been made for a-type transitions
      with K(a)</=19, J</=61. The b-type transitions were too weak to be observed.
      Upper state spectroscopic constants including the sextic terms have been obtained
      from a set of unperturbed data employing the Watson A-reduced Hamiltonian in the
      I(r) representation. A number of perturbed transitions have been accounted for,
      including b- and c-type Coriolis resonances and anharmonic resonances between
      nu(4) and the nearby levels nu(5)+nu(12) and nu(11)+nu(12). The vibrational
      energies of these perturbing levels have been obtained from the reanalysis of the
      low-resolution infrared spectrum. Rotational constants and the band origin of the
      perturbers along with the interaction parameters with the v(4)=1 state have also
      been determined. Copyright 2001 Academic Press. 

PMID- 11336519
TI  - High Resolution FTIR Study on NH(2)Cl Molecule: Inversion and Anharmonicity.
AB  - The high-resolution FTIR absorption spectra of the NH(2)Cl molecule have been
      measured in the region 500-3600 cm(-1). The rotational structures of all the
      fundamental bands and a number of overtone and combination bands have been
      analyzed. Every rotational line of the observed bands except the NH(2) twisting
      and stretching fundamental bands splits into two components due to the amino
      inversion motion. The vibrational anharmonicity and the direction of the
      transition moments have been studied with the help of B3LYP/6-31++G(**)
      calculations. The amount of inversion splitting depends on the molecular
      rotation, and the J,K-dependence of the inversion splitting has been determined.
      Copyright 2001 Academic Press. 

PMID- 11336520
TI  - The v(1)+v(3) Bands of the (16)O(17)O(16)O and (16)O(16)O(17)O Isotopomers of
      Ozone.
AB  - Using 0.002 cm(-1) resolution Fourier transform absorption spectra of an (17)O
      enriched ozone sample, an extensive analysis of the v(1)+v(3) bands of the
      (16)O(17)O(16)O and (16)O(16)O(17)O isotopomers of ozone has been performed for
      the first time. The experimental rotational levels of the (101) vibrational
      states were satisfactorily reproduced using a Hamiltonian matrix that takes into
      account the observed rovibrational resonances. More precisely, for
      (16)O(17)O(16)O, as for the other C(2v)-type ozone isotopomers, it was necessary
      to account for the Coriolis type resonances linking the (101) rotational levels
      with the levels of the (200) and (002) vibrational states and the Darling
      Dennison interaction coupling the levels of (200) with those of (002). For the
      C(s)-type isotopomer, namely (16)O(16)O(17)O, as for (16)O(16)O(18)O and
      (16)O(18)O(18)O, it proved necessary to also account for an additional
      DeltaK(a)&equals+/-2 resonance involving the rotational levels from (101) and
      (002) (J.-M. Flaud and R. Bacis, Spectrochimica Acta Part A 54, 3-16 (1998)).
      Using a Hamiltonian matrix which takes these resonances explicitly into account,
      precise vibrational energies and rotational and coupling constants were deduced,
      leading to the following band centers: v(0)(v(1)+v(3))=2078.3496 cm(-1) for
      (16)O(17)O(16)O and v(0)(v(1)+v(3))=2098.8631 cm(-1) for (16)O(16)O(17)O.
      Copyright 2001 Academic Press. 

PMID- 11336521
TI  - Torsional Splittings in Small-Amplitude Vibrational Fundamental States of
      Methanol-Type Molecules.
AB  - Group-theoretical methods are used to show that inverted torsional splittings in
      fundamental levels of small-amplitude vibrations of methanol-like molecules can
      be parameterized and understood in terms of the energy level patterns induced
      when a pair of high-barrier torsionally split components of given v(t) and
      (t)A+(t)E symmetry species in the molecular symmetry group G(6) is allowed to
      interact with small-amplitude vibrational modes of symmetry (v)E. Such doubly
      degenerate (v)E vibrational modes arise rather naturally in G(6) (isomorphic with
      the point-group C(3v)) for those methyl-group vibrations in point-group-C(s)
      asymmetric tops such as CH(3)-CHO that are analogs of the degenerate methyl-group
      stretch, bend, and rocking vibrations in point-group-C(3v) symmetric tops such as
      CH(3)-C identical withC-H. The present group-theoretical treatment is somewhat
      different from, but (as a comparison of model parameters shows) still
      fundamentally similar to, the recent local mode explanation of inverted torsional
      splittings in the C-H stretching fundamental region in methanol. Copyright 2001
      Academic Press. 

PMID- 11336522
TI  - Microwave Spectroscopic Study of NiF in the Electronic Ground and Lowest Excited
      States.
AB  - The rotational spectra of NiF in the electronic ground (2)Pi state and the lowest
      electronically excited (2)Sigma state have been observed. The source of nickel
      atom was sputtering from a nickel electrode or nickel powder placed on a
      stainless steel electrode. The molecular constants have been determined by a
      least-squares analysis of the observed transition frequencies. The rapid increase
      in the Lambda-type splittings in the ground state reveals that the observed
      rotational transitions are ascribed to the spin substate (2)Pi(3/2). The
      rotational transitions corresponding to the other substate,(2)Pi(1/2), have not
      been observed. The large spin-rotation interaction constant gamma in the
      electronically excited (2)Sigma state is consistent with that from the electronic
      spectroscopy. Copyright 2001 Academic Press. 

PMID- 11336523
TI  - High Resolution FTIR Spectroscopy of DCCCl: Anharmonic Resonances in the nu(1)
      and nu(2) Bands.
AB  - High-resolution infrared spectra of the nu(1) and nu(2) bands of DCCCl were
      observed using Bruker IFS 120HR Fourier transform spectrometers at resolutions of
      0.0044 and 0.0035 cm(-1), respectively. For the DCC(35)Cl isotopomer, the nu(1)
      as well as the nu(2) band was found to be heavily perturbed. Detailed analyses
      revealed that the nu(1) state is in resonance with the l=0 substate of the
      nu(3)+4nu(4) state and that the nu(2) state is in resonance with the l=0 substate
      of the nu(3)+4nu(5) state. The rotational constants played a key role in
      identifying the perturbing states. In contrast, for the DCC(37)Cl isotopomer, the
      rotational structures of the nu(1) and nu(2) states are almost regular but
      slightly perturbed by interactions with the nu(3)+4nu(4) and nu(3)+4nu(5) states,
      respectively. The constants of resonances as well as the molecular constants for
      the nu(1), nu(2), nu(3)+4nu(4) and nu(3)+4nu(5) states were determined. Copyright
      2001 Academic Press. 

PMID- 11336524
TI  - Rotational Spectrum of Sarin.
AB  - As part of an effort to examine the possibility of using molecular-beam Fourier
      transform microwave spectroscopy to unambiguously detect and monitor chemical
      warfare agents, we report the first observation and assignment of the rotational
      spectrum of the nerve agent Sarin (GB) (Methylphosphonofluoridic acid 1-methyl
      ethyl ester, CAS #107-44-8) at frequencies between 10 and 22 GHz. Only one of the
      two low-energy conformers of this organophosphorus compound (C(4)H(10)FO(2)P) was
      observed in the rotationally cold (T(rot)<2 K) molecular beam. The experimental
      asymmetric-rotor ground-state rotational constants of this conformer are
      A=2874.0710(9) MHz, B=1168.5776(4) MHz, C=1056.3363(4) MHz (Type A standard
      uncertainties are given, i.e., 1sigma), as obtained from a least-squares analysis
      of 74 a-, b-, and c-type rotational transitions. Several of the transitions are
      split into doublets due to the internal rotation of the methyl group attached to
      the phosphorus. The three-fold-symmetry barrier to internal rotation estimated
      from these splittings is 677.0(4) cm(-1). Ab initio electronic structure
      calculations using Hartree-Fock, density functional, and Moller-Plesset
      perturbation theories have also been made. The structure of the lowest-energy
      conformer determined from a structural optimization at the MP2/6-311G(**) level
      of theory is consistent with our experimental findings. Copyright 2001 Academic
      Press. 

PMID- 11336525
TI  - Restudy of the Ground Vibrational State of Hydrazine Using the Generalized IAM
      like Treatment for the Amino-Wagging Tunneling Motion.
AB  - The amino-wagging tunneling process in hydrazine was treated using the
      generalized IAM-like method developed by Hougen and Coudert, and Hamiltonian
      matrix elements were derived for each symmetry species in the combined group
      theoretical and IAM-like treatment. Ground state microwave absorption transition
      data of hydrazine were least squares analyzed again in this treatment to
      determine axis switching angles for the amino-wagging tunneling process.
      Copyright 2001 Academic Press. 

PMID- 11336526
TI  - High-Resolution Infrared Spectrum of CD(3)CN: Analysis of the Interacting nu(3)
      and nu(6) Bands and Evaluation of the A(0) Constant.
AB  - The infrared spectrum in the range 900-1230 cm(-1) including the fundamental
      bands nu(3) and nu(6) of CD(3)CN has been studied. The resolution attained was
      0.0025 cm(-1) in the measurement on the Bruker 120 HR Fourier spectrometer in
      Oulu. About 4000 lines were assigned in the nu(6) band. For the weak nu(3) band,
      which has not been observed earlier directly, we were able to assign 206 lines in
      three subbands K=8-10. These lines become detectable due to the strong
      nu(3)/nu(6) Coriolis resonance. There is also an l(1,-2) resonance between nu(3)
      and nu(6), which made it possible to obtain a value 2.647721(50) cm(-1) for the
      axial rotational constant A(0), when D(0)(K) from force field calculations was
      applied. Different types of resonances with the overtone 3nu(8) and the
      combinations nu(4)+nu(8) and nu(7)+nu(8) were observed. A fit with a standard
      deviation of 0.0019 cm(-1) was attained by using a model of 10 different
      resonances. Copyright 2001 Academic Press. 

PMID- 11336527
TI  - Molecular Constants for the v=0, b(1)Sigma(g)(+) Excited State of O(2): Improved
      Values Derived from Measurements of the Oxygen A-Band Using Intracavity Laser
      Spectroscopy.
AB  - High-resolution intracavity laser spectroscopy (ILS) absorption measurements have
      been made on the b-X oxygen electronic transition (the A-band) which has
      bandheads occurring in the region of 13 165 cm(-1). The positions of the lines
      were determined to an accuracy that is based on calibration with I(2) absorption
      lines using the Laboratoire Aime Cotton (Orsay) Atlas as reference. Based on the
      ILS measurements and the more accurately determined positions given by L. R.
      Brown and C. Plymate (J. Mol. Spectrosc. 199, 166-179 (2000)) and with the
      (3)Sigma(g)(-) ground state molecular constants fixed at the values determined by
      G. Rouille et al. (J. Mol. Spectrosc. 154, 372-382 (1992)), the following values
      (in cm(-1)) were found for the molecular constants: T(0)=13122.2524(1);
      B(0)=1.391244(2); D(0)=5.352(4)x10(-6); and H(0)=-1.2(2)x10(-11). These results
      are compared with values derived from fits of the line positions listed in
      several other studies of this transition. Copyright 2001 Academic Press. 

PMID- 11336528
TI  - Anomalous Vibrational Dependence of the Rotational and Hyperfine Parameters in
      the B(4)Pi-X(4)Sigma(-) Transition of NbO.
AB  - The laser excitation spectrum of jet-cooled NbO in the region 16 000-18 000 cm(
      1) has been recorded at high resolution, giving rotational and hyperfine
      constants for the levels v=0-3 of the B(4)Pi state and v=1 of the X(4)Sigma(-)
      state; zero gaps have also been measured at low resolution for some weaker bands
      involving higher vibrational levels. Taken together with the laser data for the B
      X (0,0) band from Adam et al. (J. Chem. Phys. 94, 6240-6262 (1994)) and the
      Fourier transform emission data for the doublet manifold from Launila et al. (J.
      Mol. Spectrosc. 186, 131-143 (1997)), the new data give a very complete picture
      of the vibrational energy level pattern in this region. Strong irregularities in
      the vibrational dependences of the B(4)Pi rotational and hyperfine constants can
      be interpreted in terms of spin-orbit interaction between the B(4)Pi state and
      the f(2)Pi, e(2)Phi, and d(2)Delta states. The interaction is strong enough that
      all three doublet states can be seen in absorption from the X(4)Sigma(-) ground
      state, adding to the complexity of the spectrum. The hitherto unknown
      sigmadeltasigma* (4)Delta state is estimated to lie near 17 500 cm(-1), from the
      change of sign in the spin-rotation parameter gamma of the B(4)Pi state between
      v=2 and 3. Copyright 2001 Academic Press. 

PMID- 11336529
TI  - Stabilized Tunable Diode Laser Measurements of the P(2) Line in the (13)CO
      Fundamental Band Broadened by Helium at Temperatures between 11.5 and 298.6 K.
AB  - We determined accurate He-broadening parameters and collisional cross sections
      for the P(2) line in the fundamental band of CO at room temperature and at
      intermediate temperatures down to 11.5 K. We also determined a precise value for
      the temperature dependence of the line-broadening parameter on (T)(-n) with n
      equal to 0.548+/-0.010. Our results validate the microwave results for the J=1 to
      J=2 rotational transitions measured over the same range of temperatures which
      were reported previously by Beaky et al. (1996, J. Chem. Phys. 105, 3994-4004).
      Copyright 2001 Academic Press. 

PMID- 11336530
TI  - Improved Data Set for the Herzberg Band Systems of (16)O(2).

PMID- 11336531
TI  - A Note on the Torsional Assignment of the a-Dipole Rotational Spectra for Excited
      States of CH(2)DSH and CHD(2)SH.

PMID- 11336532
TI  - Improved Molecular Constants for the Ground State of DO(2).

PMID- 11336533
TI  - Molecular Constants for the B(1)Pi and X(1)Sigma States of YCl.

PMID- 11336534
TI  - Direct measurement of erythrocyte deformability in diabetes mellitus with a
      transparent microchannel capillary model and high-speed video camera system.
AB  - To measure erythrocyte deformability in vitro, we made transparent microchannels
      on a crystal substrate as a capillary model. We observed axisymmetrically
      deformed erythrocytes and defined a deformation index directly from individual
      flowing erythrocytes. By appropriate choice of channel width and erythrocyte
      velocity, we could observe erythrocytes deforming to a parachute-like shape
      similar to that occurring in capillaries. The flowing erythrocytes magnified 200
      fold through microscopy were recorded with an image-intensified high-speed video
      camera system. The sensitivity of deformability measurement was confirmed by
      comparing the deformation index in healthy controls with erythrocytes whose
      membranes were hardened by glutaraldehyde. We confirmed that the crystal
      microchannel system is a valuable tool for erythrocyte deformability measurement.
      Microangiopathy is a characteristic complication of diabetes mellitus. A decrease
      in erythrocyte deformability may be part of the cause of this complication. In
      order to identify the difference in erythrocyte deformability between control and
      diabetic erythrocytes, we measured erythrocyte deformability using transparent
      crystal microchannels and a high-speed video camera system. The deformability of
      diabetic erythrocytes was indeed measurably lower than that of erythrocytes in
      healthy controls. This result suggests that impaired deformability in diabetic
      erythrocytes can cause altered viscosity and increase the shear stress on the
      microvessel wall.

PMID- 11336535
TI  - P2y1 and P2y2 receptor-operated Ca2+ signals in primary cultures of cardiac
      microvascular endothelial cells.
AB  - Intracellular Ca2+ signals elicited by nucleotide agonists were investigated in
      primary cultures of rat cardiac microvascular endothelial cells using the fura-2
      technique. UTP increased the intracellular [Ca2+] in 94% of the cells, whereas
      2MeSATP was active in 32%. The rank order of potency was ATP = UTP > 2MeSATP and
      the maximal response to 2MeSATP was lower compared to UTP and ATP. ATP and UTP
      showed strong homologous and heterologous desensitization. ATP fully inhibited
      the 2MeSATP response, while UTP abolished 2MeSATP-elicited transients in 25% of
      cells. 2MeSATP did not desensitize the UTP or ATP response. Adenosine 2',5'
      diphosphate inhibited the response to 2MeSATP, while it did not modify the
      response to ATP and UTP. 2MeSATP was more sensitive to suramin than UTP and ATP.
      These results indicate that P(2Y1) and P(2Y2) receptors may be coexpressed in
      CMEC. Nucleotide-induced Ca2+ signals lacked a sustained plateau and were almost
      independent from extracellular Ca2+. ATP and UTP elicited Ca2+ transients longer
      than 2MeSATP-evoked transients. The kinetics of Ca2+ responses was not affected
      by bath solution stirring or ectonucleotidase inhibition. Furthermore, the
      nonhydrolyzable ATP analogue AMP-PNP induced Ca2+ signals similar to those
      elicited by ATP and UTP. These results suggest that the distinct kinetics of
      nucleotide-evoked Ca2+ responses do not depend on the activity of
      ectonucleotidases or ATP autocrine stimulation. The possibility that Ca2+ signals
      with different time courses may modulate different cellular responses is
      discussed.

PMID- 11336536
TI  - Histamine-induced production of interleukin-6 and interleukin-8 by human coronary
      artery endothelial cells is enhanced by endotoxin and tumor necrosis factor
      alpha.
AB  - In this study, we tested the synergy between histamine and LPS, and histamine and
      TNF-alpha, on endothelial cell production of interleukin-6 (IL-6), interleukin-8
      (IL-8), and monocyte chemoattractant protein-1 (MCP-1). Human coronary artery
      endothelial cells (HCAEC) were cultured in vitro with histamine (0.1 to 1000
      microM) in the presence or absence of LPS or TNF-alpha for 24 h, and the secreted
      IL-6, IL-8 and MCP-1 were quantified. Unactivated HCAEC produced minimal levels
      of IL-6, IL-8, or MCP-1. The incubation of HCAEC with histamine resulted in low
      level induction of IL-6 and IL-8 production, which was dose-dependent and
      attained a plateau at a concentration of 10 microM. On the other hand, histamine
      failed to induce MCP-1 production. Stimulation of HCAEC with LPS or TNF-alpha
      caused dose-dependent increase in cytokine production. In the presence of all
      stimulatory concentrations of LPS and TNF-alpha tested, histamine was shown to
      further enhance IL-6 and IL-8 production. The effect of histamine on endothelial
      cell production of cytokines was completely inhibited by the H-1 receptor
      antagonist, diphenhydramine, and not by the H-2 antagonist, famotidine.
      Electrophoretic mobility shift assays of nuclear proteins extracted from HCAEC
      treated with histamine and LPS, or histamine and TNF-alpha, revealed amplified
      translocation of NF-kappaB proteins to the nuclei. Since both LPS and TNF-alpha
      potentiated histamine-induced cytokine production, it is possible that these
      activators stimulate H-1 receptor expression and/or augment the signal
      transduction pathways leading to the expression of IL-6 and IL-8. These results
      indicate the importance of synergy between histamine and other inflammatory
      stimuli on endothelial cell activation and implicate their cooperative
      participation in vascular leak and inflammation.

PMID- 11336537
TI  - Sickle erythrocytes adhere to fibronectin-thrombospondin-integrin complexes
      exposed by thrombin-induced endothelial cell contraction.
AB  - Vascular damage appears to be associated with sickle erythrocyte (SS RBC)
      adherence to the endothelium. Thrombin, which has been found in abnormal levels
      in many sickle patients, causes endothelial cell (EC) retraction and increased SS
      RBC adherence, and SS RBC adhere in the gaps opened between the EC. Our objective
      was to elucidate the mechanism of adherence to activated EC monolayers and to
      determine whether the matrix proteins thrombospondin (TSP) and fibronectin (FN)
      are mediators of this adherence. Thrombin activation elicited the same 2.5-fold
      increase in adherence whether 10 or 35% of the matrix was exposed, and the
      majority of the RBC adhered at the edges of the EC regardless of the extent of
      matrix exposed. Using static adherence assays we investigated whether TSP, FN, or
      the integrins alpha(v)beta(3) and alpha(5)beta(1) mediated adherence. Blocking
      antibodies to any of these four had no effect on adherence to untreated
      monolayers. However, all the increased adherence elicited by thrombin was
      abrogated by each one, whereas control antibodies had no effect.
      Immunofluorescent microscopy demonstrated that both integrins were present on the
      luminal surface of confluent EC. Neither TSP nor FN was exposed in confluent
      cultures but they both became available as receptors after EC retraction. These
      data suggest that SS RBC adhere to a complex of matrix TSP and FN maintained in
      an adhesive conformation by interactions with both integrins.

PMID- 11336538
TI  - Generation of superoxide anion impairs histamine-induced increases in
      macromolecular efflux.
AB  - The first goal of this study was to determine the effect of generation of
      superoxide anion using pyrogallol on histamine-induced increases in
      macromolecular efflux. We used intravital microscopy and fluorescein
      isothiocyanate-dextran (FITC-dextran; MW 70K) to examine macromolecular
      extravazation from postcapillary venules in the hamster cheek pouch in response
      to histamine before and following topical application of vehicle or pyrogallol.
      Extravazation of macromolecules was quantitated by counting venular leaky sites.
      Histamine elicited reproducible increases in venular leaky sites before and
      during infusion of vehicle. In contrast, topical application of pyrogallol (0.5
      mM) abolished histamine-induced increases in formation of venular leaky sites.
      Our second goal was to examine whether pyrogallol-induced inhibition of venular
      leaky site formation could be reversed by superoxide dismutase. Application of
      superoxide dismutase (300 U/ml) to the cheek pouch in the presence of pyrogallol
      restored histamine-induced increases in venular leaky sites. Thus, the generation
      of superoxide anion alters histamine-induced increases in macromolecular efflux.
      These results support the concept that disease states that produce oxidative
      stress may impair agonist-induced increases in microvascular permeability via
      inactivation of nitric oxide.

PMID- 11336539
TI  - Preparation of intramural small coronary artery and arteriole segments and
      resistance artery networks from the rat heart for microarteriography and for in
      situ perfusion video mapping.

PMID- 11336540
TI  - Isolation of tumor-derived endothelial cells.

PMID- 11336541
TI  - The Whitewater Arroyo virus: natural evidence for genetic recombination among
      Tacaribe serocomplex viruses (family Arenaviridae).
AB  - The Tacaribe serocomplex (family Arenaviridae) comprises three phylogenetic
      lineages, designated A, B, and C. The sequence of a 3278-nt fragment of the small
      genomic segment of the Whitewater Arroyo (WWA) virus was determined to extend our
      knowledge on the phylogenetic relationship of this newly discovered North
      American Tacaribe complex virus to other arenaviruses. Independent analyses of
      full-length nucleoprotein (N) and glycoprotein precursor (GPC) amino acid
      sequences indicated that the WWA virus N and GPC genes are descended from a
      lineage A virus and lineage B virus, respectively. The different phylogenetic
      histories of the N and GPC genes indicate that the WWA virus genome is a product
      of recombination between two Tacaribe complex viruses.

PMID- 11336542
TI  - Hepatitis C virus core protein transactivates insulin-like growth factor II gene
      transcription through acting concurrently on Egr1 and Sp1 sites.
AB  - The possibility that hepatitis C virus core gene product (HCV-core) acts as a
      transactivator in insulin-like growth factor II (IGF-II) gene transcription was
      tested. HCV-core protein increases endogenous IGF-II expression from promoter 4
      (P4) of the IGF-II gene through two cis-acting elements: Sp1 and Egr1 binding
      sites. Sp1 and Egr1 both bind to IGF-II P4 and functionally cooperate in
      mediating the maximal activity of IGF-II P4. HCV-core protein induced the binding
      of Sp1 and Egr1 on its binding sites on IGF-II P4. In addition, Sp1 and Egr1 were
      stimulated to phosphorylate by HCV-core, and its DNA binding activity was up
      regulated upon HCV-core transfection. Transfection with HCV-core in HepG2 cells
      stimulated the membrane translocation of protein kinase C (PKC) and the treatment
      of HCV-core transfected cells with calphostin C, a PKC inhibitor, blocked
      induction of Sp1 and Egr1 DNA binding activity, and eventually transcriptional
      transactivations of the IGF-II gene. Increasing the DNA binding activity of the
      phosphorylated form of Sp1 and Egr1 might be an important mechanism for
      regulating IGF-II gene expression and for promoting cell division during hepatic
      carcinogenesis. These results indicate that HCV-core functions as a positive
      regulator of IGF-II transcription through the PKC pathway and that Sp1 and Egr1
      are direct targets of the transcriptional regulation of the IGF-II gene which
      plays an important role in hepatitis C virus pathogenesis during the formation of
      hepatocellular carcinoma (HCC).

PMID- 11336543
TI  - Hepatitis C virus core protein enhances FADD-mediated apoptosis and suppresses
      TRADD signaling of tumor necrosis factor receptor.
AB  - Hepatitis C virus (HCV) core protein has been shown to interact with the death
      domain (DD) of tumor necrosis factor receptor-1 (TNFR1). In this study, we
      further examined the interaction of the core protein with the signaling molecules
      of TNFR1, including FADD, TRADD, and TRAF2, in a human embryonic kidney cell
      line, HEK-293, that overexpresses the HCV core protein. This core protein
      expressing cell line exhibited enhanced sensitivity to TNF-induced apoptosis. By
      in vitro binding and in vivo coimmunoprecipitation assays, we showed that the HCV
      core protein interacted with the DD of FADD and enhanced apoptosis induced by
      FADD overexpression. This enhancement could be blocked by a dominant-negative
      mutant of FADD. In contrast, the core protein did not directly interact with the
      DD of TRADD, but could disrupt the binding of TRADD to TNFR1. TRAF2 recruitment
      to the TNFR1 signaling complex was also disrupted by the core protein.
      Correspondingly, TRAF2-dependent activation of the protein kinase JNK was
      suppressed in the core protein-expressing cells. However, NF kappa B activation
      by TNF was not significantly altered by the HCV core protein, suggesting the
      existence of TRAF2-independent pathways for NF kappa B activation. These results
      combined indicate that the HCV core protein sensitizes cells to TNF-induced
      apoptosis primarily by facilitating FADD recruitment to TNFR1. The inhibition of
      JNK activation by the HCV core protein may also contribute to the increased
      propensity of cells for apoptosis. These results, in comparison with other
      published studies, suggest that the effects of the HCV core protein and their
      underlying mechanisms vary significantly among cells of different origins.

PMID- 11336544
TI  - RhoA is activated during respiratory syncytial virus infection.
AB  - Respiratory syncytial virus (RSV) is an important human pathogen that can cause
      severe and life-threatening respiratory infections in infants and
      immunocompromised adults. We have recently shown the RSV F glycoprotein, which
      mediates viral fusion and entry, interacts with the cellular protein RhoA in two
      hybrid and in vitro binding assays. Whether this interaction occurs in living
      cells remains an open question. However, because RhoA signaling is associated
      with many cellular functions relevant to RSV pathogenesis such as actin
      cytoskeleton organization, expression of proinflammatory cytokines, and smooth
      muscle contraction, we asked whether RhoA activation occurred during RSV
      infection of HEp-2 cells. We found that the amount of isoprenylated and membrane
      bound RhoA in RSV-infected cultures was increased. Further evidence of RhoA
      activation was demonstrated by downstream signaling activity mediated by RhoA.
      There was an increase in p130(cas) phosphorylation during RSV infection, which
      was prevented by Y-27632, a specific inhibitor of Rho kinase, or lovastatin, an
      HMG-CoA reductase inhibitor that reduces the synthesis of groups needed for
      isoprenylation. In addition, RSV infection of HEp-2 cells resulted in an increase
      in the formation of actin stress fibers. Pretreatment of HEp-2 cells with
      Clostridium botulinum C3 exotoxin, an enzyme that specifically ADP-ribosylates
      and inactivates RhoA, prevented RSV-induced stress fiber formation. These
      observations indicate that RhoA and subsequent downstream signaling events are
      activated during RSV infection, which has implications for RSV pathogenesis.

PMID- 11336545
TI  - The long repeat region is dispensable for fowl adenovirus replication in vitro.
AB  - Two regions containing tandemly repeated sequences are present in the fowl
      adenovirus 9 (FAdV-9) genome. The longer repeat region (TR-2) is composed of 13
      contiguous 135-bp-long direct repeats, the function of which is unknown. An
      infectious FAdV-9 genomic clone, constructed by homologous recombination in
      Escherichia coli, was used for engineering of recombinant viruses. The enhanced
      green fluorescence protein (EGFP) coding sequence was cloned in both rightward
      and leftward orientations so as to replace TR-2. Replication-competent
      recombinant FAdVs were recovered, demonstrating that TR-2 was dispensable for
      FAdV-9 propagation in vitro. The expression of EGFP in infected cells was
      demonstrated by fluorescence microscopy, immunoprecipitation, and RT-PCR.

PMID- 11336546
TI  - Induction of Tax i expression in MT-4 cells by 5-azacytidine leads to protein
      binding in the HTLV-1 LTR in vivo.
AB  - The Tax I trans-activator protein of the human T-cell leukemia virus I (HTLV-I)
      enhances viral gene expression through enhancer sequences in the viral LTR. These
      sequences consist of three imperfect 21-bp repeats (TRE-1) and a region between
      the promoter central and promoter proximal TRE-1 (known as TRE-2). We have
      previously described the in vivo footprint of the HTLV-I TRE-1s and TRE-2 in two
      HTLV-I-infected cell lines, MT-2 and MT-4. MT-2 is a high-level producer of virus
      and shows significant DNA-protein interactions within the TRE-1s and TRE-2. In
      contrast, the proviral DNA in MT-4 cells is heavily methylated and produces no
      detectable virus. In this report, we describe the footprints of the TRE-1s and
      TRE-2 in MT-4 cells that were induced to express high levels of viral proteins by
      treatment with 5-azacytidine, a potent inhibitor of methylation. The footprints
      of the TRE-1s in 5-azacytidine-treated MT-4 cells were virtually identical to
      those observed in MT-2 cells. In contrast, the footprints within the TRE-2 region
      of 5-azacytidine-treated MT-4 cells did not resemble those in either MT-2 or MT-4
      cells.

PMID- 11336547
TI  - Tioman virus, a novel paramyxovirus isolated from fruit bats in Malaysia.
AB  - A search for the natural host of Nipah virus has led to the isolation of a
      previously unknown member of the family Paramyxoviridae. Tioman virus (TiV) was
      isolated from the urine of fruit bats (Pteropus hypomelanus) found on the island
      of the same name off the eastern coast of peninsular Malaysia. An electron
      microscopic study of TiV-infected cells revealed spherical and pleomorphic
      enveloped viral particles (100--500 nm in size) with a single fringe of embedded
      peplomers. Virus morphogenesis occurred at the plasma membrane of infected cells
      and morphological features of negative-stained ribonucleoprotein complexes were
      compatible with that of viruses in the family Paramyxoviridae. Serological
      studies revealed no cross-reactivity with antibodies against a number of known
      Paramyxoviridae members except for the newly described Menangle virus (MenV),
      isolated in Australia in 1997. Failure of PCR amplification using MenV-specific
      primers suggested that this new virus is related to but different from MenV. For
      molecular characterization of the virus, a cDNA subtraction strategy was employed
      to isolate virus-specific cDNA from virus-infected cells. Complete gene sequences
      for the nucleocapsid protein (N) and phosphoprotein (P/V) have been determined
      and recombinant N and V proteins produced in baculovirus. The recombinant N and V
      proteins reacted with porcine anti-MenV sera in Western blot, confirming the
      serological cross-reactivity observed during initial virus characterization. The
      lack of a C protein-coding region in the P/V gene, the creation of P mRNA by
      insertion of 2-G residues, and the results of phylogenetic analyses all indicated
      that TiV is a novel member of the genus Rubulavirus.

PMID- 11336549
TI  - Comparative genomics of lactococcal phages: insight from the complete genome
      sequence of Lactococcus lactis phage BK5-T.
AB  - Lactococcus lactis phage BK5-T and Streptococcus thermophilus phage Sfi21, two
      cos-site temperate Siphoviridae with 40-kb genomes, share an identical genome
      organization, sequence similarity at the amino acid level over about half of
      their genomes, and nucleotide sequence identity of 60% over the DNA packaging and
      head morphogenesis modules. Siphoviridae with similarly organized genomes and
      substantial protein sequence similarity were identified in several genera of low
      GC-content Gram-positive bacteria. These phages demonstrated a gradient of
      relatedness ranging from nucleotide sequence similarity to protein sequence
      similarity to gene map similarity over the DNA packaging and head morphogenesis
      modules. Interestingly, the degree of relatedness was correlated with the
      evolutionary distance separating their bacterial hosts. These observations
      suggest elements of vertical evolution in phages. The structural genes from BK5-T
      shared no sequence relationships with corresponding genes/proteins from
      lactococcal phages belonging to distinct lactococcal phage species, including
      phage sk1 (phage species 936) that showed a closely related gene map. Despite a
      clearly distinct genome organization, lactococcal phages sk1 and c2 showed nine
      sequence-related proteins. Over the early gene cluster phage BK5-T shared nine
      regions of high nucleotide sequence similarity, covering at most two adjacent
      genes, with lactococcal phage r1t (phage species P335). Over the structural
      genes, the closest relatives of phage r1t were not lactococcal phages belonging
      to other phage species, but Siphoviridae from Mycobacteria (high-GC-content Gram
      positive bacteria). Evidence for recent horizontal gene transfer between distinct
      phage species was obtained for dairy phages, but these transfers were limited to
      phages infecting the same bacterial host species.

PMID- 11336548
TI  - The V protein of human parainfluenza virus 2 antagonizes type I interferon
      responses by destabilizing signal transducer and activator of transcription 2.
AB  - Type I interferon (IFN) induces antiviral responses through the activation of the
      ISGF3 transcription factor complex that contains the subunit proteins STAT1,
      STAT2, and p48/ISGF3 gamma/IRF9. The ability of some human paramyxoviruses to
      overcome IFN actions by specific proteolysis of STAT proteins has been examined.
      Infection of cells with type 2, but not type 1 or type 3 human parainfluenza
      virus (HPIV) leads to a loss of cellular STAT2 protein. Expression of a single
      HPIV2 protein derived from the V open reading frame blocks IFN-dependent
      transcriptional responses in the absence of other viral proteins. The loss of IFN
      response is due to V-protein-induced proteolytic degradation of STAT2. Expression
      of HPIV2 V causes the normally stable STAT2 protein to be rapidly degraded, and
      this proteolytic activity can be partially alleviated by proteasome inhibition.
      No V-protein-specific effects on STAT2 mRNA levels were observed. The results
      indicate that the V protein of HPIV2 is sufficient to recognize and target a
      specific cellular transcription factor for destruction by cellular machinery.

PMID- 11336550
TI  - Domains in the simian immunodeficiency virus gp41 cytoplasmic tail required for
      envelope incorporation into particles.
AB  - The mechanism by which lentivirus envelope (Env) glycoproteins are packaged into
      budding virions is poorly understood. Simian immunodeficiency virus (SIV)
      contains an Env protein with an unusually long cytoplasmic tail. To investigate
      the role of this domain in the incorporation of the SIV Env into virions, we
      generated a series of SIV Env mutants carrying small in-frame deletions within
      the cytoplasmic domain. The effects of these mutations on Env synthesis,
      processing, and association with Gag particles were analyzed by means of the
      vaccinia virus expression system. All of the mutant Env glycoproteins were
      synthesized and processed in a manner similar to that of the wild-type Env.
      However, deletions affecting domains C-terminal to residue 832 in the SIV Env
      protein significantly impaired Env incorporation into particles. Cell surface
      biotinylation assays showed that this phenotype could not be attributed to
      inefficient cell surface expression of the Env mutants. Furthermore, when the Env
      deletion mutants were tested for their ability to mediate virus entry in single
      cycle infectivity assays, those mutations that impaired Env incorporation also
      caused a severe defect in virus infectivity. Our results suggest that domains in
      the C-terminal third of the SIV Env protein are required for Env incorporation
      into particles and Env-mediated virus entry.

PMID- 11336551
TI  - Functional activity of HERV-K-T47D-related long terminal repeats.
AB  - The human genome contains a family of endogenous retroviruses, HERV-K(HML-4),
      that comprises the full-length provirus HERV-K-T47D, five related elements, and
      hundreds of solitary long terminal repeats (LTRs). We here show that HERV-K-T47D
      related LTRs are dispersed over all human chromosomes and have arisen after the
      divergence of Old and New World monkeys. By screening a cDNA library derived from
      the human mammary carcinoma cell line T47D with a HERV-K-T47D LTR probe, we
      isolated several clones containing LTR/cellular gene chimeras and assessed the
      transcriptional activity of these LTRs in transient transfection experiments. All
      LTRs were able to drive the expression of a reporter gene, thereby displaying
      distinct activities in different cell lines. We found that sequences located
      downstream of the LTR-U3 region modulate the level of gene expression. Based on
      the impact of the R region we distinguished between three different LTR types;
      the activity of type I LTRs was enhanced in the presence of the LTR-R region in
      all cell lines tested, whereas a type II LTR was downregulated. Type III LTRs are
      characterized by lacking or having a varying influence of the R region that was
      dependent on the cell line used. Finally, our results attribute to LTR-U5-gag
      sequences a role in determining LTR activity.

PMID- 11336552
TI  - Herpes simplex virus 1 ICP27 is required for transcription of two viral late
      (gamma 2) genes in infected cells.
AB  - The herpes simplex virus infected cell protein 27 (ICP27) is required for the
      expression of certain early viral proteins and for many late proteins during
      productive infection. Expression of at least one late (gamma 2) gene, that
      encoding glycoprotein C, is severely restricted in the absence of functional
      ICP27. The exact mode of action by which ICP27 induces late gene expression is
      not known, but the effect is apparent at the mRNA level as demonstrated by
      Northern blot analysis. To determine whether ICP27 activates late genes via
      transcriptional or posttranscriptional mechanisms, we initially used nuclear run
      on assays to measure transcription of viral genes in Vero cells infected with
      wild-type (WT) virus or an ICP27 nonsense mutant virus, n504. We observed a 4
      fold reduction in the nuclear run-on signal from the coding strand of the gC gene
      for n504-infected cells compared to that of WT-infected cells. However,
      interpretation of the results was complicated by the observation of a significant
      signal from the noncoding strand in these experiments. To obviate the problem of
      symmetrical transcription, we utilized in vivo RNA pulse-labeling to measure the
      amount of transcription of viral genes in cells infected with either WT virus or
      n504 virus. We found a 5- to 10-fold reduction in the transcription of the gC and
      U(L)47 genes, two late genes, in cells infected with n504 compared to that in
      cells infected with WT virus. In contrast, transcription of the ICP8 gene, an
      early gene, was similar in WT and n504 virus-infected cells. We also examined the
      stability of the gC and U(L)47 gene transcripts in n504-infected cells, and we
      found it to be comparable to that in WT virus-infected cells, further supporting
      an effect on transcription. Transcription of the gC and U(L)47 genes by n504 was
      normal in a cell line that expresses WT ICP27. From these results we conclude
      that ICP27 is required for transcription of the late gC and U(L)47 genes during
      productive infection.

PMID- 11336553
TI  - Potyviral helper-component proteinase expressed in transgenic plants enhances
      titers of Potato leaf roll virus but does not alleviate its phloem limitation.
AB  - Coinfection of Nicotiana benthamiana with Potato virus A (PVA, a potyvirus) and
      Potato leaf-roll virus (PLRV, a luteovirus) induces a synergistic interaction
      manifested by enhanced titers of PLRV. The helper component proteinase (HC-Pro)
      of potyviruses is involved in viral vascular movement and suppression of an
      antiviral defense mechanism in plants. Data of our study showed that accumulation
      of PLRV in transgenic N. benthamiana expressing the PVA HC-Pro was enhanced on
      average by 4.5-fold, as compared to a 6.0-fold enhancement in wild-type N.
      benthamiana plants doubly infected with PVA and PLRV. Enhancement of PLRV
      accumulation was directly proportional to the concentration of the HC-Pro in
      leaves. In the HC-Pro-transgenic plants and wild-type plants, PLRV was almost
      exclusively confined to the phloem, but the HC-Pro-transgenic plants had a
      fourfold greater number of PLRV-infected cells within the phloem tissues, as
      revealed by immunohistochemical staining. In the leaves doubly infected with PLRV
      and PVA, PLRV was found to exit the phloem in 25.0% of the veins, infecting all
      types of leaf cells, but, on average, PLRV accumulation was not enhanced more
      than by sixfold at the whole-leaf level. Therefore, potyviral/luteoviral
      synergism seems to be based on two mechanisms. One of them is mediated by the HC
      Pro and increases luteovirus accumulation without allowing detectable egress from
      vascular tissue. The other mechanism probably depends on additional potyviral
      proteins and alleviates the normal phloem limitation of PLRV.

PMID- 11336554
TI  - Evolution of AZT resistance in HIV-1: the 41-70 intermediate that is not observed
      in vivo has a replication defect.
AB  - The human immunodeficiency virus type 1 (HIV-1) is notorious for its ability to
      evolve drug-resistance in patients treated with potent antivirals. Resistance to
      inhibitors of the viral reverse transcriptase (RT) enzyme is frequently mediated
      by a single amino acid substitution within RT. Resistance against the nucleoside
      analogue AZT is remarkable in that multiple amino acid changes accumulate over
      time to yield virus variants with high-level drug resistance. We now report that
      in addition to drug-resistance properties, the relative replication capacity of
      the virus variants affects the evolution of AZT resistance. Some of the typical
      AZT-resistance mutations have a negative impact on virus replication, and the 41
      70 double mutant was found to represent a particularly poor virus. Furthermore,
      introduction of additional AZT-resistance mutations (41-70-215) leads to nearly
      complete restoration of virus replication. These results may explain the absence
      of the 41-70 double mutant in clinical samples and indicate that the evolution of
      AZT resistance is also influenced by virus replication parameters. Prolonged
      passage of the replication-impaired 41-70 virus in the absence of AZT yielded
      several fast-replicating variants. These revertants have compensatory changes in
      the RT polymerase, some of which have been observed previously in AZT-treated
      patients. Because we could select for these changes without drug pressure, these
      changes are likely to improve the RT enzyme function and the HIV-1 replication
      capacity.

PMID- 11336555
TI  - Two regions of the P protein are required to be active with the L protein for
      human parainfluenza virus type 1 RNA polymerase activity.
AB  - The paramyxovirus P protein is an essential component of the viral RNA polymerase
      composed of P and L proteins. In this study, we characterized the physical and
      functional interactions between P and L proteins using human parainfluenza virus
      type 1 (hPIV1) and its counterpart Sendai virus (SV). The hPIV1 P and SV L
      proteins or the SV P and hPIV1 L proteins formed complexes detected by anti-P
      antibodies. Functional analysis using the minigenome SV RNA containing CAT gene
      indicated that the hPIV1 P--SV L complex, but not the SV P--hPIV1 L complex, was
      biologically active. Mutant SV P or hPIV1 P cDNAs, which do not express C
      proteins, showed the same phenotype with wild-type P cDNAs, indicating that C
      proteins are not responsible for the dysfunction of SV P--hPIV1 L polymerase
      complex. Using the chimeric hPIV1/SV P cDNAs, we identified two regions (residues
      387--423 and 511--568) on P protein, which are required for the functional
      interaction with hPIV1 L. These regions overlap with a previously identified
      domain for oligomer formation and binding to nucleocapsids. Our results indicate
      that in addition to a P--L binding domain, hPIV1 L requires a specific region on
      P protein to be biologically functional as a polymerase.

PMID- 11336556
TI  - Reactivation of feline foamy virus from a chronically infected feline renal cell
      line by trichostatin A.
AB  - Although acute infection of feline foamy virus (FeFV) is normally highly
      cytopathogenic in Crandell feline kidney (CRFK) cells, a noncytopathic persistent
      infection was established in the cells after cocultivation of the initially
      infected cells with uninfected cells four times. To investigate reactivation of
      persistent infection, CRFK cells chronically infected with FeFV were treated with
      trichostatin A (TA), a histone deacetylase inhibitor. TA induced higher FeFV
      production from the Coleman strain carrier culture and also induced marked
      syncytium formation. In contrast, human foamy virus, which contains less
      homologous long terminal repeat (LTR) and putative internal promoter (IP)
      sequences, persistently infecting baby hamster kidney cells was not reactivated
      by TA. The Sammy-1 strain of FeFV, from which a part of the U3 region in the LTR
      is naturally deleted, showed less reactivation. The Coleman LTR promoter-based
      beta-Gal-expressing plasmid was activated in the persistently Coleman-infected
      cells in the presence of TA, whereas the Sammy-1 LTR was not activated.
      Furthermore, the amounts of Gag protein expressed did not change in the presence
      or absence of TA. Because the putative IP region was very similar between the two
      strains, the initiation by TA is relatively specific for LTR sequences, and,
      therefore, histone deacetylation is at least in part responsible for reactivation
      of FeFV from carrier cell culture.

PMID- 11336557
TI  - High virus loads in naturally and experimentally SIVagm-infected African green
      monkeys.
AB  - A quantitative RT-PCR assay was developed for SIVagm and was used to measure the
      levels of viral RNA in the plasma of experimentally and naturally infected
      African green monkeys. The number of productively infected PBMCs and the number
      of cells carrying integrated provirus were also measured. Plasma virus loads in
      experimentally infected animals peaked at 2 weeks postinfection, ranging from 2.9
      x 10(5) to 4.2 x 10(7) RNA copies/ml plasma. Set points of 2.1 x 10(3) to 2.8 x
      10(6) RNA copies/ml plasma were maintained for one year. Similarly, the number of
      cells carrying integrated SIVagm provirus remained relatively stable in
      individual animals for one year with set points ranging from 73 to 810 proviral
      copies per 10(6) PBMC. However, the number of productively infected cells
      fluctuated considerably during this period. Virus loads in the 26 naturally
      infected AGMs ranged from 8.3 x 10(3) to 1.1 x 10(7) (mean 1.7 x 10(6)) RNA
      copies/ml plasma. These levels of viremia are similar to those seen in pathogenic
      systems (HIV-1, SIVmac), indicating that control of SIVagm replication is not the
      reason for the natural host's resistance to disease progression.

PMID- 11336558
TI  - Carbohydrate modifications of the NDV fusion protein heptad repeat domains
      influence maturation and fusion activity.
AB  - The amino acid sequence of the fusion protein (F) of Newcastle disease virus
      (NDV) has six potential N-linked glycosylation addition sites, five in the
      ectodomain (at amino acids 85, 191, 366, 447, and 471) and one in the cytoplasmic
      domain at amino acid 542. Two of these sites, at positions 191 and 471, are
      within heptad repeat (HR) domains implicated in fusion activity of the protein.
      To determine glycosylation site usage as well as the function of added
      carbohydrate, each site was mutated by substituting alanine for the serine or
      threonine in the addition signal. The sizes of the resulting mutant proteins,
      expressed in Cos cells, showed that sites at amino acids 85, 191, 366, and 471
      are used. This conclusion was verified by comparing sizes of mutant proteins
      missing all four used sites with that of unglycosylated F protein. The role of
      each added oligosaccharide in the structure and function of the F protein was
      determined by characterizing stability, proteolytic cleavage, surface expression,
      and fusion activity of the mutant proteins. Elimination of the site in F(2) at
      amino acid 85 had the most detrimental effect, decreasing cleavage, stability,
      and surface expression as well as fusion activity. The protein missing the site
      at 191, at the carboxyl terminus of the HR1 domain, also showed modestly reduced
      surface expression and negligible fusion activity. Proteins missing sites at 366
      and 471 (within HR2) were expressed at nearly wild-type levels but had decreased
      fusion activity. These results suggest that all carbohydrate side chains,
      individually, influence the folding or activity of the NDV F protein.
      Importantly, carbohydrate modifications of the HR domains impact fusion activity
      of the protein.

PMID- 11336559
TI  - Membrane relocation but not tight binding of human immunodeficiency virus type 1
      Gag particles myristoylated in Escherichia coli.
AB  - Expression of human immunodeficiency virus Gag protein and the N-terminal matrix
      (MA) domain in Escherichia coli yielded spherical structures in the cytoplasm.
      When human N-myristoyltransferase was coexpressed, both Gag and MA were fully
      myristoylated and spherical structures were relocated in close proximity to the
      cytoplasmic membrane. However, neither myristoylated Gag nor MA exhibited tight
      binding to E. coli membrane, suggesting that myristoylation in E. coli did not
      confer membrane affinity on Gag despite the relocation. Our data also suggest
      that the morphogenetic pathway of Gag particles in prokaryotic cells differs from
      that in eukaryotic cells despite biochemical similarities of in the form of Gag
      expressed.

PMID- 11336560
TI  - Induction of type-specific neutralizing antibodies by capsomeres of human
      papillomavirus type 33.
AB  - The immunogenicity of capsomeres of human papillomavirus type 33 was evaluated in
      a dose-response analysis. Capsomeres were obtained free of capsids by expression
      of L1 carrying the single point mutation C427S. Neutralizing antibodies were
      detected using an in vitro pseudoinfection assay. Capsomeres induced type
      specific, neutralizing antibodies in mice even in the absence of adjuvant. The
      neutralization titers of immune sera raised without adjuvant were 10- to 20-fold
      lower than those of antisera to virus-like particles, but virtually identical
      using Freund's adjuvant. These data indicate that capsomeres may substitute for
      virus-like particles in future vaccines when used with an adjuvant appropriate
      for human vaccination.

PMID- 11336561
TI  - Molecular characterization of Menangle virus, a novel paramyxovirus which infects
      pigs, fruit bats, and humans.
AB  - Menangle virus (MenV), isolated in August 1997 following an outbreak of
      reproductive disease in a piggery in New South Wales, is the second previously
      unclassified member of the family Paramyxoviridae to be identified in Australia
      since 1994. Similar to Hendra virus (HeV), MenV appears to be a virus of fruit
      bats (flying foxes) in the genus Pteropus. No serological cross-reactivity was
      detected between MenV and other known paramyxoviruses and to facilitate virus
      classification a cDNA subtraction method was used to obtain viral-specific cDNA
      from MenV-infected cells. Cloning and sequencing of the products enabled the
      entire sequences of the NP, P/V, M, F, and HN genes to be determined. Comparison
      of the nucleotide and deduced amino acid sequences for each gene with members of
      the family Paramyxoviridae, determination of the P gene mRNA editing strategy,
      and phylogenetic analyses confirmed that MenV is a new member of the genus
      Rubulavirus. However the deduced protein sequence of MenV HN exhibited only
      limited sequence homology when compared with attachment proteins of other
      paramyxoviruses. Key differences within the amino acid residues considered
      important determinants of neuraminidase activity suggest MenV HN is unlikely to
      possess the same degree of neuraminidase activity characteristic of other
      rubulavirus and respirovirus HN proteins.

PMID- 11336562
TI  - 5'-coterminal subgenomic RNAs in citrus tristeza virus-infected cells.
AB  - Three unusual 5' coterminal positive-stranded subgenomic (sg) RNAs, two of about
      0.8 kb and one of 10 kb (designated LMT1, LMT2, and LaMT, respectively), from
      Citrus spp. plants and Nicotiana benthamiana protoplasts infected with Citrus
      tristeza virus (CTV) were characterized. The 5' termini of the LMT RNAs were
      mapped by runoff reverse transcription and found to correspond with the 5'
      terminus of the genomic RNA. The LMT 5'-coterminal sgRNAs consisted of two modal
      lengths of 744--746 and 842--854 nts. The 3' of the LaMT RNAs terminated near the
      junction of ORF 1b and ORF 2 (p33). None of the 5' sgRNAs had detectable amounts
      of corresponding negative-sense RNAs, as occurs with the genomic and 3'
      coterminal subgenomic RNAs of CTV. The abundance of the short and long 5' sgRNAs
      differed considerably in infected cells. The LMT RNAs were considerably more
      abundant than the genomic RNAs, while the larger LaMT RNA accumulated to much
      lower levels. The kinetics of accumulation of LMT1 and LMT2 in synchronously
      infected protoplasts differed. The larger RNA, LMT1, accumulated earlier with a
      strong hybridization signal at 2 days postinfection, a time when only traces of
      genomic and 3' sgRNAs were detected. The lack of corresponding RNAs, that could
      be 3' cleavage products corresponding to the 5' coterminal sgRNAs and the lack of
      complementary negative strands, suggest that these sgRNAs were produced by
      termination during the synthesis of the genomic positive strands.

PMID- 11336563
TI  - Anti-inflammatory drugs, cyclooxygenases and other factors.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs), which for so many years have
      played major roles in treating inflammation, pain and fever, have had major
      recent boosts to various therapeutic aspects. These include the impetus generated
      by the cyclooxygenase (COX)-2 inhibitors celecoxib and rofecoxib, a greater
      understanding of NSAID non-prostaglandin modes of action and the use of NSAIDs in
      cancer and Alzheimer's disease. Many of these aspects are covered in articles in
      this issue of Expert Opinion on Pharmacotherapy.

PMID- 11336564
TI  - Drugs, inflammation and cell adhesion receptors.
AB  - The cell adhesion receptors that participate in the extravasation and migration
      of leucocytes towards inflammatory foci mainly include the selectins and
      different members of the integrin and immunoglobulin superfamilies. These
      adhesion receptors mediate the sequential steps of leucocyte-endothelial cell
      interaction and, together with chemoattractant molecules (e.g., chemokines),
      direct the influx of inflammatory cells and define the characteristics of the
      cell infiltrate. Many different drugs, including non-steroidal anti-inflammatory
      drugs (NSAIDs), glucocorticoids, rheumatoid arthritis disease-modifying agents
      and phosphodiesterase inhibitors, interfere with the expression and/or function
      of cell adhesion receptors and this effect accounts for, at least in part, their
      anti-inflammatory activity. In recent years, novel approaches for the modulation
      of the cell membrane receptors involved in inflammation have been active areas in
      pharmaceutical research. Upgraded synthetic blocking compounds, chimeric
      monoclonal antibodies or improved antisense oligonucleotides represent important
      advances in this field. The proper development of these novel approaches, as well
      as other alternative strategies, will allow a better and more specific
      pharmacological modulation of the inflammatory phenomenon.

PMID- 11336565
TI  - Intelligent use of NSAIDs--where do we stand?
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) are drugs commonly prescribed for
      a variety of medical conditions. They are potent pharmacological agents
      efficacious for inflammatory conditions, but have significant gastrointestinal
      (GI), renal and haematological toxicity that must not be taken lightly. The
      newer, more cyclooxygenase-(COX)-2-selective NSAIDs, have no effects on platelet
      function and little GI toxicity, but do have renal physiological effects. The
      superiority of one NSAID over another has not been clinically demonstrated in
      musculoskeletal conditions, nor has the efficacy of NSAIDs in non-inflammatory
      rheumatic conditions been shown to be better than that of simple analgesics.
      NSAIDs are indicated for primary therapy of inflammatory rheumatic diseases and
      the more selective COX-2 agents should be employed as first choice when
      economically feasible. NSAIDs should not be used indiscriminately for non
      inflammatory osteoarthritis or musculoskeletal injuries, particularly in the
      elderly patient, in whom alternative, less toxic therapy should be sought.

PMID- 11336566
TI  - COX-2 inhibitors vs. NSAIDs in gastrointestinal damage and prevention.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit production of protective
      gastric mucosal prostaglandins and also have a direct topical irritant effect. In
      some patients this results in dyspepsia and development of gastroduodenal
      erosions and ulceration. The risk of ulcer complications, such as bleeding,
      perforation and death is increased approximately 4-fold in NSAID users. Patients
      at high risk of ulcer complications include the elderly, those taking
      anticoagulants, steroids and aspirin, those with a previous history of peptic
      ulceration and patients with concomitant serious medical problems. The
      interaction of NSAIDs with Helicobacter pylori (the major cause of peptic
      ulceration in non-NSAID users) is controversial and some studies suggest that H.
      pylori infection may even protect against NSAID-induced ulceration. Selective
      inhibitors of the inducible cyclooxygenase-2 (COX-2) enzyme spare COX-1 in the
      gastric mucosa and, hence, do not inhibit production of mucosal prostaglandins.
      COX-2-selective inhibitors are associated with a significant reduction in
      gastroduodenal damage compared with traditional NSAIDs. Proton pump inhibitors
      (PPI) are probably the best agents for healing and prevention of NSAID-induced
      ulcers. Preliminary studies suggest that COX-2 selective inhibitors, like
      traditional NSAIDs, may prevent lower gastrointestinal cancer. Further studies
      are needed but they may be useful in individuals at high risk of certain types of
      lower gastrointestinal malignancy with increased gastrointestinal tolerability
      and safety.

PMID- 11336567
TI  - Treatment of anal fissures with topical nitroglycerin.
AB  - Anal fissure is a painful condition that is caused by anodermal tearing after the
      passage of hard stool. Severe cases result in involuntary internal anal sphincter
      spasm and have traditionally been treated surgically with a lateral
      sphincterotomy. Investigators have demonstrated that nitric oxide causes
      relaxation of the smooth muscle of the anal canal, so topical nitroglycerin
      ointment preparations have recently been studied as an efficacious alternative to
      surgery. Despite the fact that there are a number of trials examining topical
      nitroglycerin for the treatment of anal fissures, there remains no consensus
      about concentrations, compositions and applications necessary to obtain good
      results. This review summarises current literature regarding topical
      nitroglycerin pharmacotherapy for anal fissure.

PMID- 11336568
TI  - Leukotriene inhibitors and non-steroidal therapies in the treatment of asthma.
AB  - Asthma is the most common chronic disease of childhood whose morbidity and
      mortality continues to rise [1]. Drugs used in the treatment of asthma must be
      targeted at reversing three principle pathophysiologic features:
      bronchoconstriction, mucus plugging/hypersecretion and inflammation. In the past
      two decades, the contribution of airway inflammation to the development and
      progression of asthma symptoms and airway pathology has become a critical focus.
      Chronic airway inflammation can lead to the progressive decline and irreversible
      loss of lung function and airway remodelling [2]. In recent years, therapies
      aimed at diminishing airway inflammation have been at the forefront of asthma
      management. Steroids have been extensively studied and used as primary anti
      inflammatory agents in the management of the asthmatic patient with persistent
      symptoms of varying severity. Within the last decade, however, several additional
      non-steroidal classes of drugs have begun to emerge as anti-inflammatory agents
      for the treatment of asthma. This article will focus on these non-steroidal drugs
      which have been developed and investigated within the last 5 years. Particular
      emphasis will be placed on leukotriene receptor antagonists, but anti-IgE and
      anti-IL-4 therapies, as well as phosphodiesterase inhibitors will also be
      discussed. Of these new therapies, only two leukotriene receptor antagonists,
      montelukast (Singulairtrade mark, Merck) and zafirlukast (Accolatetrade mark,
      AstraZeneca) and the 5-lipoxygenase inhibitor, zileuton (Zyflotrade mark, Abbott
      Laboratories), have been recommended, approved and are currently available for
      use in the treatment of paediatric patients with asthma in the United States.

PMID- 11336569
TI  - Intravenous immunoglobulin therapy for the treatment of severe atopic dermatitis.
AB  - Intravenous immunoglobulin (IVIg) is standard therapy for primary
      immunodeficiencies, Kawasaki Disease and idiopathic thrombocytopenic purpura.
      More recently, the use of high dose IVIg (2 g/kg in divided doses) has widened to
      include a number of inflammatory diseases, including atopic eczema. The mechanism
      of IVIg's anti-inflammatory action has yet to be fully understood. Proposed
      mechanisms include modulation of IgE responses and a reduction in inflammatory
      cytokines with a reduction in T-cell proliferation. Antibacterial and antitoxin
      effects may also play a role.

PMID- 11336570
TI  - TNF blockade in the treatment of rheumatoid arthritis: infliximab versus
      etanercept.
AB  - There is accumulating evidence that tumour necrosis factor (TNF) plays a major
      role in the pathogenesis of rheumatoid arthritis (RA). Recent biotechnological
      advances have allowed for the development of agents that directly target TNF, a
      pro-inflammatory cytokine. In the last 2 years, the US FDA and the EU's
      Commission of the European Communities have approved two biological agents for
      the treatment of refractory RA, etanercept and infliximab. Etanercept is a fusion
      protein, composed of the Fc portion of IgG1 and the extracellular domain of the
      TNF receptor (p75). Infliximab is a chimeric monoclonal antibody (mAb) composed
      of murine variable and human constant regions. In placebo-controlled trials, both
      agents have proven to be effective and well-tolerated in RA patients. This review
      evaluates the available TNF inhibitors, summarises pertinent clinical trials and
      underscores differences between the two agents in terms of molecular structure,
      efficacy, safety data, antigenicity and pharmacokinetics.

PMID- 11336571
TI  - Current use of biologicals for the treatment of spondyloarthropathies.
AB  - Spondyloarthropathies (SpA) are a group of related disorders. The hallmark
      symptoms include spondylitis, pauci-articular synovitis and enthesiopathy. In an
      important number of cases, subclinical gut inflammation with pathological
      findings resembling Crohn's disease can be found. Some of these patients may
      eventually develop overt Crohn's disease. Conventional medical therapy in
      patients with SpA consists of non-steroidal anti-inflammatory drugs (NSAIDs).
      Sulphasalazin can be co-administered, especially in cases of chronic synovitis or
      enthesiopathy. Recently, experience with anti-TNF-alpha monoclonal antibodies
      (infliximab), a new class of biological compounds, has opened new avenues for
      treating patients with SpA. In particular, infliximab used in two open studies
      gave significant benefit on the locomotor manifestations in patients with Crohn's
      disease, in patients with ankylosing spondylitis, undifferentiated SpA and
      psoriatic arthritis. Etanercept, another TNF-alpha antagonist (soluble receptor),
      was shown to induce benefit in a placebo-controlled study in patients with
      psoriatic arthritis. The relationship between SpA and inflammatory bowel disease
      lead to the hypothesis that interfering with gut inflammation in patients with
      SpA would yield a potential target for modulating the synovitis in these
      patients. Thus, besides TNF-alpha blockade, other strategies with potential
      efficacy can be envisioned, such as IL-10, ICAM-1 antisense or anti-(4)beta(7)
      antibodies.

PMID- 11336572
TI  - The role of nitric oxide in penile erection.
AB  - The functional state of the penis, flaccid or erect is governed by smooth muscle
      tone. Sympathetic contractile factors maintain flaccidity whilst parasympathetic
      factors induce smooth muscle relaxation and erection. It is generally accepted
      that nitric oxide (NO) is the principal agent responsible for relaxation of
      penile smooth muscle. NO is derived from two principal sources: directly from non
      adrenergic non-cholinergic parasympathetic nerves and indirectly from the
      endothelium lining cavernosal sinusoids and blood vessels in response to
      cholinergic stimulation. The generation of NO from L-arginine is catalysed by
      nitric oxide synthase (NOS). There has been controversy over the relative
      prevalence of endothelial or neuronal NOS within the penis of different animal
      species. This review examines the role of NO in the penis in detail. Established
      and new treatments for erectile dysfunction whose effects are mediated via
      manipulation of the NO pathway are also described.

PMID- 11336573
TI  - Current treatment for ovarian cancer.
AB  - Ovarian cancer is the most lethal gynaecologic malignancy. Epithelial ovarian
      cancer (EOC) constitutes approximately 90% of cases of ovarian cancer and 70% of
      the patients with EOC present in advanced stage. Treatment of EOC usually
      consists of cytoreductive surgery which includes total abdominal hysterectomy
      (TAH), bilateral salpingo-oophorectomy (BSO), omentectomy and lymphadenectomy
      followed by adjuvant chemotherapy. Current adjuvant chemotherapy includes
      paclitaxel and either cisplatin or carboplatin given every 3 weeks for six
      cycles. The combination paclitaxel and platinum chemotherapy achieves clinical
      response in approximately 80% of patients. However, most patients will have
      tumour recurrence within 3 years following treatment. Patients with platinum
      sensitive tumours can be re-treated with platinum and/or paclitaxel. Those with
      platinum-resistant tumours have poor prognosis and treatment is palliative.
      Options of treatment in these patients include topotecan, doxil, gemcitabine,
      etoposide, or enrolment in clinical trials. Future research needs to focus on the
      role of cytoreductive surgery, second-look surgery, consolidation chemotherapy,
      development of new chemotherapeutic agents, chemoresistance modulators, as well
      as new approaches to the treatment of women with ovarian cancer.

PMID- 11336574
TI  - Leflunomide: a novel DMARD for the treatment of rheumatoid arthritis.
AB  - Leflunomide (Arava(trade mark), Hoescht Marion Roussel, now Aventis Pharma) is a
      new, oral disease modifying antirheumatic drug (DMARD) for the treatment of
      active rheumatoid arthritis (RA). It is a novel isoxazole derivative, which has
      shown both anti-inflammatory and immunomodulatory properties. Leflunomide
      primarily acts by inhibiting the de novo synthesis of pyrimidine nucleotides (and
      consequently DNA and RNA) in immune response cells, particularly activated T
      cells. It also inhibits tyrosine kinases, with a subsequent reduction in the pro
      inflammatory cytokines, TNF and IL-1. Leflunomide is significantly more effective
      than placebo and equivalent to sulfasalazine and methotrexate in short-term (26 -
      52 week) studies, as measured by American College of Rheumatology (ACR) criteria.
      It has shown significant improvements in functional disability and health related
      quality of life and has consistently been shown to slow radiographic progression
      of RA. Leflunomide has a rapid onset of action (within 4 weeks) which is
      significantly faster than placebo and sulfasalazine. Leflunomide was well
      tolerated in clinical trials with no serious adverse effects occurring. The most
      common side effects were gastrointestinal disturbances, reversible alopecia,
      rash, hypertension and abnormal liver function tests. Most of these were mild to
      moderate and resolved without any complications. In summary leflunomide is an
      effective and well-tolerated DMARD that is a welcome addition to the currently
      available DMARDs for the treatment of this disabling condition.

PMID- 11336575
TI  - Celecoxib: a new option in the treatment of arthropathies and familial
      adenomatous polyposis.
AB  - The discovery of the two isoenzymes of cyclooxygenase (COX) has recently lead to
      the development and clinical introduction of specific inhibitors of
      cyclooxygenase-2 (COX-2), such as celecoxib, onto the market. Celecoxib is an
      effective anti-inflammatory, analgesic and antipyretic agent therapeutically
      utilised in the management of osteoarthritis and rheumatoid arthritis. In
      addition, celecoxib has some novel therapeutic and pharmacological activities.
      Celecoxib inhibits anti-apoptotic kinase activation and is the first specific COX
      2 inhibitor to be marketed for familial adenomatous polyposis, an inheritable
      predisposition for colorectal cancer. Celecoxib is not without gastrointestinal
      (GI) side effects but demonstrates markedly reduced GI ulceration in clinical
      trials when compared to traditional non-specific non-steroidal anti-inflammatory
      drugs (NSAIDs). The specific COX-2 inhibitors each have distinctive
      pharmacokinetic properties. Celecoxib can be given either once or twice daily.
      Racial differences in drug disposition, and pharmacokinetic changes in elderly
      patients, patients with chronic renal insufficiency and patients with mild to
      moderate hepatic impairment, are evident with celecoxib. Despite the specific
      action of these drugs, there remains the potential for significant drug
      interactions. Celecoxib has demonstrated interactions with fluconazole, lithium
      and warfarin. Increased clinical vigilance should be maintained when co
      prescribing medications with celecoxib until further clinical experience is
      gained. Celecoxib represents a major therapeutic advance in terms of GI safety.
      However, long-term safety in other organ systems, safety with concomitant drug
      administration, and pharmacoeconomic benefits still remain to be proven.

PMID- 11336576
TI  - Pharmacology and clinical experience with simvastatin.
AB  - Simvastatin (Zocortrade mark, Merck) is a safe and effective 3-hydroxy-3
      methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor. Simvastatin potently
      lowers total and low density lipoprotein (LDL) cholesterol. Simvastatin was the
      first cholesterol-lowering agent that reduced total mortality in a randomised
      clinical trial. Simvastatin is effective at reducing total mortality, myocardial
      infarction, coronary mortality and the incidence of stroke or transient ischemic
      attack in patients with coronary heart disease and hypercholesterolemia.
      Simvastatin, like other statins, also has non-lipid mechanisms of action. These
      include anti-inflammatory effects, antiproliferative effects on smooth muscle
      cells and an upregulation of endothelial nitric oxide synthase. Overall,
      simvastatin has an excellent safety profile. Simvastatin, along with other
      statins, has made a significant impact on the morbidity and mortality from
      coronary heart disease.

PMID- 11336577
TI  - Amlodipine/benazepril: fixed dose combination therapy for hypertension.
AB  - Myocardial infarction, stroke, heart failure and end-stage renal disease have all
      been linked to inadequate control of blood pressure. Despite overwhelming
      evidence that uncontrolled hypertension is responsible for a sizeable number of
      adverse health-related outcomes, control of the disease remains considerably
      suboptimal. Available data demonstrate that in order to achieve adequate blood
      pressure control, a large number of patients require therapy with more than one
      medication. Fixed dose combination antihypertensive therapy has many advantages
      over other treatment options. Positive effects on blood pressure control, rates
      of adherence, adverse effects and cost have been identified.
      Amlodipine/benazepril (Lotrel), Novartis) is a fixed dose combination product
      indicated for the treatment of hypertension. Although not currently recommended
      as first-line therapy, studies confirm that this combination of a long-acting
      calcium antagonist and an angiotensin-converting enzyme (ACE) inhibitor possesses
      substantial blood pressure lowering capabilities. Whereas adverse events tend to
      become more frequent with increasing doses of antihypertensive monotherapy, the
      rate of adverse events attributed to amlodipine/benazepril in clinical trials
      often correlates with rates ascribed to placebo. Amlodipine/benazepril is capable
      of sustaining blood pressure control over a 24 h period and appears to be
      minimally affected by an occasional dose omission. Unlike the older calcium
      antagonists, amlodipine is unlikely to cause alterations in myocardial
      contractility. Additionally, the amlodipine/benazepril combination product costs
      less than the same therapy administered as the individual components. It is,
      therefore, reasonable to consider therapy with amlodipine/benazepril in
      appropriate patients after an adequate trial of antihypertensive monotherapy.

PMID- 11336578
TI  - Pharmacology and clinical experience with tiagabine.
AB  - Tiagabine (TGB), a recently approved anti-epileptic drug (AED), has a specific
      and unique mechanism of action involving the inhibition of gamma-aminobutyric
      acid (GABA) re-uptake into neurones and glia. TGB is potent and has linear and
      predictable pharmacokinetics. It does not induce or inhibit hepatic metabolism
      and has no clinically significant effects on the serum concentrations of other
      AEDs or commonly used non-AEDs. Double-blind, placebo-controlled studies in
      primarily hepatic enzyme-induced patients showed that TGB 30 - 56 mg/day is an
      effective add-on treatment for all subtypes of partial seizures. The most common
      adverse effects in the trials were dizziness, asthenia (weakness), somnolence,
      accidental injury, infection, headache, nausea and nervousness. These side
      effects were usually mild to moderate in severity and generally did not require
      medical intervention. Long-term safety studies show continued efficacy of TGB
      over time and no evidence of tolerance for efficacy. Open studies confirm that
      patients with medically refractory partial epilepsy can be successfully converted
      to TGB monotherapy and that TGB may be effective for other seizure types, such as
      infantile spasms.

PMID- 11336579
TI  - Antimicrobial resistance--should we be concerned?
AB  - Simply stated, the use of antibiotics is the root cause of antimicrobial
      resistance. Without antibiotic use, there would be no widespread selection of
      antibiotic resistant bacteria and, thus, no antimicrobial resistance. So if the
      problem is as simple as stopping the use of antibiotics, or even restricting the
      use of antibiotics, what is the fuss about? How about adding perhaps the
      potential for an additional 3-6 million deaths or more annually worldwide to the
      1.3 million deaths from Mycobacterium tuberculosis alone? So concerning the
      matter of antimicrobial resistance- should we be concerned? Absolutely, yes.

PMID- 11336580
TI  - A pharmacoeconomic appraisal of therapies for hepatitis B and C.
AB  - In the recent years, advances in the treatment of chronic hepatitis B and C have
      shown that newer, more expensive therapy may result in higher sustained viral
      response rates. In light of this, the pertinent question for healthcare decision
      makers centres around whether this increase in efficacy 'justifies' the
      additional cost. Pharmacoeconomics is dedicated to helping answer these types of
      questions. In this article, we will discuss the clinical aspects of hepatitis B
      and C, recent advances in treatment and studies of the cost-effectiveness of
      these treatments.

PMID- 11336581
TI  - Human herpesvirus 6: its impact and influence on infectious diseases and their
      management.
AB  - Human herpesvirus (HHV)-6 was discovered 15 years ago and was then grouped as a
      member of the family human herpesviridae. Its first clinical manifestation was
      identified 2 years later as the agent responsible for exanthem subitum. With the
      advent of newer molecular techniques, its diagnosis is easier and prospective
      studies have shown that it is the most common pathogen responsible for febrile
      illness in infants. In some infants, it is associated with febrile convulsions.
      Two subtypes, A and B, have been identified, B subtype commonly being responsible
      for primary infection in infants. Primary infection in healthy adults is rare.
      Most of the clinical manifestations are mild, self-limiting and rarely fatal.
      Reactivation of HHV-6 is frequently found in bone marrow as well as solid organ
      transplant recipients. HHV-6 has been shown to be an independent risk factor
      responsible for recurrence of cytomegalovirus infection, especially in solid
      organ transplants. In bone marrow transplant recipients, HHV-6 has been
      associated with various manifestations like marrow suppression and graft versus
      host disease, although most infections present as usually mild febrile illness
      with or without rash. It has been reported to cause encephalitis in transplant
      recipients. Although HHV-6 has been shown to be responsible for upregulation of
      HIV in vitro studies, its exact role in AIDS is yet to be defined. In addition to
      its neurotropic manifestation of febrile convulsion in infancy, it has been found
      in plaques in the brain of multiple sclerosis and progressive multifocal
      leukoencephalopathy. Further studies are needed before its role in the
      pathogenesis of these neurological illnesses can be established. Its lymphotropic
      feature was responsible for its discovery and now it has only been detected in
      some lesions of primary ocular mucosa associated lymphoid tissue lymphoma. As HHV
      6 is found to be responsible for more and more illnesses, especially causing
      serious illnesses in the immunocompromised, it is becoming necessary to find
      effective treatment. Some agents, like cidofovir and phosphonoformic acid, are
      effective in in vitro studies and some have shown effectiveness in a clinical
      setting. Further studies are needed to identify its role in the pathogenesis of
      various neurological and malignant lesions and AIDS. Various treatment regimens
      should be tested in clinical scenario and especially in immunocompromised
      transplant recipients.

PMID- 11336582
TI  - Pharmacotherapy of ascariasis.
AB  - Ascaris lumbricoides, the most frequent human intestinal nematode, is the
      causative agent of ascariasis, with an estimated worldwide prevalence of over one
      billion people, especially in moist tropical and subtropical regions, but also in
      cooler climates. Although characterised with low morbidity and mortality rates,
      the global prevalence of ascariasis still results in approximately 20,000 deaths
      annually, primarily as a consequence of intestinal obstruction. In humans,
      transmission usually occurs by hand-to-mouth route by way of contaminated
      agricultural products and food, or from dirty hands. Three phases of ascariasis
      may be present, namely, the pulmonary, intestinal and the complications stage.
      Although generally asymptomatic, heavy infestation may cause serious pulmonary
      disease, or partial or complete obstruction of biliary or intestinal tracts.
      Anthelminthic chemotherapy is required to eradicate the parasites and prevent
      potentially serious complications. Mebendazole, albendazole and pyrantel pamoate
      are the most widely used agents to treat ascariasis. Preventive chemotherapy
      delivered to communities in endemic regions may serve as an affordable and cost
      effective strategy to reduce the prevalence and morbidity in endemic regions.
      Under unusual circumstances, Ascaris suum, the cause of helminthic infection in
      pigs, may also cause disease in humans.

PMID- 11336583
TI  - Current and future treatment of Lyme disease.
AB  - Lyme borreliosis, a tick-transmitted spirochetal disease, may begin with a
      characteristic expanding skin lesion at the site of the tick bite. Within several
      days to weeks, the infection can spread haematogenously to involve the heart,
      nervous system or the joints. After months to years, the spirochete may persist
      in these organs causing a chronic form of illness. All stages of this disease can
      be treatable with antimicrobial agents.

PMID- 11336584
TI  - Helicobacter pylori infection--current treatment practice.
AB  - Helicobacter pylori infection, which is present in 30 - 60% of the population in
      developed countries and in more than 60% in developing countries, is established
      to be a major cause of gastritis, peptic ulcer disease and gastric cancer.
      Eradication therapy has been incorporated into clinical practice over the past 15
      years. Treatment regimens include a 2 week bismuth-based triple therapy (a
      bismuth compound plus metronidazole, tetracycline or amoxycillin), a 1 week
      proton-pump inhibitor (PPI)-based triple therapy and a 1 week ranitidine bismuth
      citrate (RBC)-based triple therapy (a PPI or RBC plus any two of the three
      antibiotics, metronidazole, amoxycillin and clarithromycin). These regimens
      achieve eradication rates of >> 80%. H. pylori resistance to metronidazole and
      clarithromycin decreases the clinical efficacy of most regimens, despite the high
      eradication rates for resistant strains achieved by the RBC-triple therapy in
      some recent trials. The dose of antibiotics (especially clarithromycin) and the
      duration of treatment may also influence the eradication rate. Doctors' beliefs
      impact on clinical practice and, thus, influence the clinical application of
      eradication therapy. Whereas peptic ulcer disease and primary gastric low-grade B
      cell mucosa-associated lymphoid tissue lymphoma (MALToma) have become established
      as definite indications for eradication therapy, there remain controversies
      surrounding non-ulcer dyspepsia, gastro-oesophageal reflux disease, atrophic
      gastritis, intestinal metaplasia, use of non-steroidal anti-inflammatory drugs
      (NSAIDs) and H. pylori-related extradigestive diseases.

PMID- 11336585
TI  - Chemotherapy of enterobiasis (oxyuriasis).
AB  - Enterobius vermicularis (syn. Oxyurus vermicularis), also known as pinworm or
      seatworm, is the causative agent of human enterobiasis (oxyuriasis). The disease
      is more prevalent in temperate regions and is facilitated by factors such as
      overcrowding in schools and family groupings, as well as inadequate personal and
      community hygiene. Although the infection is more likely to occur in lower
      socioeconomic groups, enterobiasis has been reported to affect virtually every
      level of the general population and especially children. In the great majority of
      cases, enterobiasis is asymptomatic. One common symptom is intense pruritus ani
      that in some patients can lead to insomnia, restlessness and irritability.
      Scratching may cause skin irritation, and in more serious cases, eczematous
      dermatitis, haemorrhage or secondary bacterial infections. Ectopic migration of
      E. vermicularis often results in pinworm infestation of the female genital tract
      often causing granulomas of the uterus, ovary and the fallopian tubes and pelvic
      peritoneum. Anthelmintic therapies for enterobiasis are successful and include
      mebendazole, albendazole and pyrantel pamoate. Mass medication of affected groups
      reduced symptoms rapidly, progressively and in a cost-effective way.

PMID- 11336586
TI  - Potential therapeutic application of antisense oligonucleotides in the treatment
      of ocular diseases.
AB  - Antisense oligonucleotides are a class of compounds being developed as
      therapeutic agents for many types of diseases. Although still relatively early in
      the clinical characterisation, the power of this technology lies in the ability
      to utilise genetic information and the known molecular mechanisms of disease to
      foster efficient and rational drug design. Consideration of novel approaches to
      treating ocular diseases is of interest because there are many ocular diseases
      with no satisfactory treatments. The recent availability of animal models of many
      ocular diseases provides the opportunity to use antisense oligonucleotides to
      understand the mechanisms of disease pathology and to potentially intervene
      therapeutically in ocular disease. There are already a number of examples where
      antisense oligonucleotides have been applied to the study of ocular physiology
      and disease and there is an antisense oligonucleotide approved for the treatment
      of cytomegalovirus (CMV) retinitis. We summarise current research in this area
      and highlight the properties of these compounds that are favourable for use as
      ocular therapeutics.

PMID- 11336587
TI  - Linezolid--a review of the first oxazolidinone.
AB  - Linezolid is the first of a truly new class of antibiotics, the oxazolidinones.
      It acts as an inhibitor of bacterial protein synthesis by blocking the formation
      of the 70S ribosomal initiation complex. Its activity is bacteriostatic against
      some species (e.g., enterococci) and bactericidal against others (e.g.,
      pneumococci). The antibacterial spectrum of linezolid includes Gram-positive
      pathogens and some Gram-negative anaerobic species but not Gram-negative aerobes.
      Importantly, multi-drug resistant organisms such as methicillin-resistant
      staphylococci, staphylococci with reduced susceptibility to vancomycin,
      penicillin- and macrolide-resistant pneumococci and vancomycin-resistant
      enterococci are fully susceptible to linezolid. Linezolid has almost 100%
      bioavailability and the area under the plasma concentration curve is identical
      after oral and iv. administration. This enables initial oral administration of
      linezolid in those patients who can absorb the drug normally and also an early
      step-down therapy from iv. to oral. Controlled, randomised clinical studies have
      documented efficacy and safety of linezolid in hospital- and community-acquired
      pneumonia, uncomplicated and complicated skin and soft tissue infections and
      infections caused by vancomycin-resistant enterococci. The safety and
      tolerability of linezolid are advantageous. Linezolid is a weak and reversible
      monoamine oxidase (MAO) inhibitor and although no increased frequency of
      adrenergic or serotonergic adverse events has been reported, it is recommended
      that linezolid is used with caution in patients treated with other MAO
      inhibitors.

PMID- 11336588
TI  - Pharmacology and clinical experience with saquinavir.
AB  - Saquinavir is a peptidomimetic inhibitor of HIV protease. Initially marketed as
      Invirasetrade mark, the effectiveness of saquinavir was greatly hindered by its
      nearly complete first pass metabolism by cytochrome P450 3A4. A new formulation,
      Fortovasetrade mark, appears to yield some six times the drug exposure and has
      been demonstrated to yield virological and immunological results similar to those
      of other protease inhibitors (PIs) when used in conjunction with two nucleoside
      reverse transcriptase inhibitors (nRTIs). Emerging data suggest it is safe to use
      twice daily. Co-administration of either formulation of saquinavir with
      nelfinavir and especially ritonavir yields greatly increased blood levels, with
      corresponding superior magnitude and durability of viral suppression in first
      line therapy, albeit with increased adverse effects. The combination of ritonavir
      and saquinavir has also yielded the most promising results published for second
      line therapy, after virological breakthrough on previous PI-containing therapy.
      In addition, preliminary data suggests the possibility of once daily dosing of
      ritonavir and saquinavir, which would be expected to increase compliance and
      allow for direct observed therapy.

PMID- 11336589
TI  - Moxifloxacin: a review of the microbiological, pharmacological, clinical and
      safety features.
AB  - Antimicrobial agents are used to treat patients with infectious diseases. Initial
      antimicrobial compounds originated from natural sources and were generally deemed
      to be narrow in spectrum. Today, we are in the era of designer drugs that have
      been specifically developed with current issues in infectious diseases in mind.
      For example, some new compounds require once daily dosing, have minimal side
      effects, are active against resistant pathogens and, for some, have a lower
      propensity for selecting for antimicrobial resistance during patient therapy.

PMID- 11336590
TI  - Moxonidine: some controversy.
AB  - Initially it was considered that moxonidine, like clonidine, acted at central (2)
      adrenoceptors to reduce blood pressure. With the characterisation of imidazoline
      binding sites distinct from (2)-adrenoceptors, the consensus became that
      moxonidine was acting predominantly at imidazoline I(1) receptors in the rostral
      ventrolateral medulla to lower blood pressure. Moxonidine acts at prejunctional
      (2)-adrenoceptors on sympathetic nerve endings to decrease noradrenaline release
      and this may contribute to its ability to lower blood pressure. The predominant
      site of action of moxonidine may also depend on route of administration, with
      imidazoline I(1) receptors being predominant after central, and (2)-adrenoceptors
      predominant after systemic administration. The controversy over the mechanism and
      site of action with moxonidine is ongoing. In animal models, moxonidine lowers
      blood pressure, reduces cardiac hypertrophy and remodelling, reduces cardiac
      arrhythmias and increases blood flow in cerebral ischaemia. Moxonidine also has
      beneficial effects in animal models of diabetes and kidney disease. Moxonidine
      increases sodium and water excretion in rats, but not humans. Animal studies
      indicate that moxonidine may be useful in the treatment of glaucoma by reducing
      intra-ocular pressure. Animal studies show that moxonidine may also be effective
      in pain and in ethanol withdrawal. In humans, the pharmacokinetics of moxonidine
      are of the one-compartment model with first-order absorption. Renal elimination
      is the major route of elimination and individual titration of moxonidine is
      needed in patients with renal impairment. There is overwhelming evidence that
      moxonidine is a safe and effective antihypertensive. A large clinical trial of
      moxonidine in heart failure, MOXCON, was stopped because of excessive deaths in
      the moxonidine group. Moxonidine should not be used in patients with heart
      failure, but there are no obvious reasons to stop its use as an antihypertensive,
      or its development for other clinical uses.

PMID- 11336591
TI  - Verteporfin: a milestone in opthalmology and photodynamic therapy.
AB  - During the past year, a photosensitiser named benzoporphyrin derivative (BPD) has
      been approved in 26 countries under the generic name verteporfin (Visudynetrade
      mark, Novartis), for the treatment of patients with a certain type of the wet
      form of age-related macular degeneration (AMD) by photodynamic therapy (PDT). AMD
      is the leading cause of blindness in the developed world, with approximately half
      a million new cases of the wet form per year. The approval of Visudynetrade mark
      therapy represents a major milestone in ophthalmology since AMD was previously
      untreatable by any modality which would preserve existing vision. It was also a
      milestone in the development of PDT, not only because it represented the first
      breakthrough in the use of PDT to treat an otherwise untreatable condition, but
      also because it represented the first mass market for a PDT treatment where
      prospects of a substantial financial return on many years of investment appear to
      be likely. In this article, we look at the background to the development of BPD,
      primarily for its use in AMD, but also in other applications.

PMID- 11336592
TI  - Pricing, profits and pharmacoeconomics--for whose benefit?
AB  - In today's troubled healthcare climate, it is not uncommon to run across
      headlines like: 'Health insurance premiums increasing by 10 percent to 30 percent
      across the country.' This particular New York Times article went on to explain
      that this premium price hike, the third consecutive double digit increase in 3
      years, is driven largely by escalating pharmaceutical costs. The pharmaceutical
      industry has largely been vilified in the media and in the recent presidential
      debates, for fueling healthcare inflation and setting what many perceive to be
      'unfair' prices in light of the profit margins on their life-saving products. A
      report released by the Congressional Research Service found that after tax,
      profits for the pharmaceutical industry averaged 17% of sales, compared with 5%
      for all other industries. The White House has added its voice to the popular
      discontent with notices such as this one reported in the New York Times: 'There
      is a rising tide politically in this country of strong antagonism against the
      pharmaceutical industry on the dimension of prices. (Without expanded access to
      insurance) price controls are an inevitable outcome.' Although the prospect of
      price control remains dubious in America's entrenched laissez-faire economy,
      David Kessler, former head of the FDA and the Dean of the Yale School of
      Medicine, described the situation as a 'powder keg,' stating 'the current system
      is simply not sustainable'. Although there does not appear to be an immediate
      solution to this escalating crisis, this editorial will examine pharmaceutical
      pricing, industry profits and the role of pharmacoeconomic analyses amidst the
      chaos.

PMID- 11336593
TI  - Current treatment practice for essential thrombocythaemia in adults.
AB  - Essential thrombocythaemia (ET) is a relatively benign chronic myeloproliferative
      disorder that occurs primarily in middle-aged patients. Its clinical course is
      characterised by thomboembolic and, less frequently, by haemorrhagic
      complications. Life expectancy of ET is generally of normal length and
      progression to acute leukaemia is a rare event. About one third of all patients
      are asymptomatic at diagnosis and many of them remain without complications for
      years. Therefore, the main challenge for treating patients with ET is to select
      patients who will benefit from a cytoreductive or antiplatelet therapy, because
      it is doubtful whether the beneficial effects of therapy outweigh the potential
      hazards in all cases. For this reason a risk stratification in high and low risk
      ET patients is essential. The treatment of ET has evolved from alkylating agents
      to hydroxyurea (HU) or pipobroman and more recently to agents such as IFN-alpha
      and anagrelide. Aspirin as an antiplatelet therapy is also expected to play a
      part in the treatment of ET. HU is first-line therapy for elderly patients with
      high risk ET. In young ET patients without ET related complications and a
      platelet count << 1000 - 1500 x 10(9)/l abstention from cytoreductive therapy or
      therapy with low-dose aspirin alone seems to be appropriate. The aim of this
      review is to address the current treatment practice for ET in adults.

PMID- 11336594
TI  - Anti-angiogenic therapy of proliferative diabetic retinopathy.
AB  - Proliferative diabetic retinopathy (PDR) remains one of the major causes of
      acquired blindness in developed nations. This is true despite the development of
      laser treatment, which can prevent blindness in the majority of those who develop
      this complication. The hallmark of PDR is neovascularisation (NV), abnormal
      angiogenesis that may ultimately cause severe vitreous cavity bleeding and/or
      retinal detachment. Pharmacologic therapy aimed at preventing NV, as an adjunct
      to laser treatment, or as an alternative to laser treatment, would be a welcome
      addition to the armamentarium. PDR could be prevented by improved metabolic
      control or by pharmacologically blunting the biochemical consequences of
      hyperglycaemia (e.g., with aldose reductase inhibitors, inhibitors of non
      enzymatic glycation or by protein kinase C (PKC) inhibition). The angiogenesis in
      PDR could be treated via growth factor (e.g., vascular endothelial growth factor
      (VEGF), insulin like growth factor-1) blockade, integrin (e.g., alpha-v beta-3)
      blockade or extracellular matrix alteration (e.g., with steroid compounds), or
      interference with intracellular signal transduction pathways (e.g., PKC and
      mitogen activated protein kinase pathway proteins). Numerous potentially useful
      anti-angiogenic compounds are in development, but two drugs are presently in
      clinical trials for the treatment of the preproliferative stage of PDR.

PMID- 11336595
TI  - The pharmacology of methotrexate.
AB  - Ectopic pregnancy (EP) is a major cause of maternal morbidity and mortality. The
      treatment of this condition is primarily surgical, but medical management in
      selected cases is safe, effective, cost-effective and eliminates the morbidity of
      surgery. Methotrexate (MTX) is a folate antagonist that can be used for non
      oncologic purposes including the treatment of EP. The dose and duration of MTX
      therapy for EP is much lower than that used in oncology cases, thus reducing side
      effects and increasing safety. MTX selectively acts on rapidly dividing cells,
      such as trophoblast cells which comprise the implantation site of the early
      gestation. The two most common methods of administering MTX to patients with EP
      are im. administration of a single-dose, based on body surface area and
      calculated by the equation 50 mg/m(2) (without the need for leucovorin rescue),
      or the multiple-dose regimen of 1 mg/kg of MTX, alternating with 0.1 mg/kg of
      leucovorin rescue. Both methods have a similar side effect profile, resulting in
      the rare occurrence of nausea, vomiting, stomatitis, elevated liver function
      tests, anorexia and diarrhoea. The two methods yield success rates similar to
      those of conservative surgical therapy with similar future fertility. The
      potential single- and multi-dose methods have never been directly compared, but
      it appears that the success of multiple dosing is more effective. As the efficacy
      of MTX therapy is not 100%, women must be followed clinically until there is
      compete resolution of human Chorionic Gonadotropin (hCG) titres from their serum.

PMID- 11336596
TI  - Lipids and atherosclerosis: clinical management of hypercholesterolaemia.
AB  - Hypercholesterolaemia is a major risk factor for the development of
      atherosclerosis which, in turn, underlies most ischaemic heart disease (IHD).
      This review deals briefly with the pathophysiology of lipids in humans and
      follows with a discussion of current lipid-lowering therapies. In those patients
      with a history of myocardial infarction (MI) or unstable angina, appropriate
      lipid-lowering therapy has been convincingly shown to reduce not only cardiac
      events but also overall mortality. The advent of the HMG CoA reductase inhibitors
      in the late 1980s has had a revolutionary impact in the clinical management of
      hypercholesterolaemia, not only because of their efficacy but especially because
      they are well-tolerated. The use of other treatments such as the fibrates and
      bile acid resins are also discussed. Given the successful use of the statins, it
      is felt that an emergence of a different class of LDL-cholesterol lowering
      compound is unlikely in the near future and rather that compounds which can
      increase HDL-cholesterol while lowering LDL will be of greater impact. There may
      also be a shifting trend towards such naturally occurring compounds as plant
      stanols and phytoestrogens.

PMID- 11336597
TI  - Clinical management of protein C deficiency.
AB  - Protein C (PC) is a vitamin K-dependent plasma protein that is structurally
      similar to other coagulation factors such as prothrombin and Factor X. PC is
      converted to its active anticoagulant form by a thrombin-thrombomodulin complex
      on the surface of capillary endothelial cells. Activated PC (APC) prevents the
      formation of blood clots by specifically inactivating factors Va and VIIIa in the
      clotting cascade. Both acquired and hereditary forms of PC deficiency exist, with
      hereditary further categorised as heterozygous, homozygous as well as doubly
      heterozygous. Patients suffering from symptomatic heterozygous PC deficiency
      present with purpura fulminans, venous thrombosis and/or pulmonary embolism.
      Homozygous PC deficiency is usually associated with the development of severe and
      often fatal, purpura fulminans and disseminated intravascular coagulation (DIC)
      during the neonatal period. Various therapeutic options have been described for
      long-term management of severe heterozygous and homozygous PC deficiencies. For
      the treatment of heterozygous PC deficiency, oral anticoagulation with a coumarin
      derivative or heparin therapy remains standard therapy. Homozygous patients may
      be treated with fresh frozen plasma (FFP) and iv. PC concentrate or coumarin
      derivatives. Other therapeutic options for the treatment of hereditary PC
      deficiency include the use of low-molecular weight heparin (LMWH), steroids and
      liver transplantation. Maintenance of a symptom-free life depends on response to
      therapy. Patients responding well to treatment can expect normalisation of
      haemostasis as well as improvement of microcirculation and resolution of purpura
      fulminans.

PMID- 11336598
TI  - Antileukotrienes in asthma: present situation.
AB  - Leukotrienes are key mediators in asthma. Over the last 5 years, several
      antileukotrienes, including three receptor antagonists (montelukast, pranlukast
      and zafirlukast) and one 5-lipoxygenase inhibitor (zileuton), have been marketed
      and, to date, this class of drugs is being used widely. Still, their definite
      place in the asthma treatment algorithm is not yet established. These novel drugs
      have not yet all been evaluated in the same depth, but they have all been shown
      to possess anti-inflammatory properties and to be effective in chronic asthma
      treatment. Zafirlukast and montelukast are particularly efficacious in exercise
      induced asthma and zileuton appears valuable for treating aspirin-intolerant
      asthmatics. Clinical comparisons to other anti-asthma drugs are still sparse. The
      corticosteroid-sparing effect of antileukotrienes is fairly well established
      except for zileuton, even though this drug has been evaluated most thoroughly in
      terms of its anti-inflammatory effects. Montelukast is the antileukotriene most
      extensively evaluated in children and zafirlukast has recently been approved for
      use in children in the USA, although not yet in Europe. Therapeutic regimes are
      quite variable depending on the drug, but all of the antileukotrienes marketed to
      date are taken orally; hence, compliance is usually greater than that with
      inhaled medication. Response to antileukotrienes appears to depend on the
      individual patients' characteristics, in particular on genetic polymorphisms
      related to leukotriene metabolism. All drugs of this class are well tolerated and
      only in the case of zileuton is there potential for hepatic adverse effects. The
      diagnosis of Churg-Strauss syndrome made among patients taking antileukotrienes
      seems to be more related to the withdrawal of corticosteroids than to the
      antileukotrienes themselves.

PMID- 11336599
TI  - Rosiglitazone.
AB  - Type 2 diabetes mellitus is characterised by impaired insulin secretion,
      diminished peripheral insulin action and increased hepatic glucose production.
      Clinical trials have indicated that near-normal glucose control may reduce the
      risk for microvascular and - to a lesser extent - macrovascular complications in
      Type 2 diabetic patients. Thiazolidinediones improve insulin action by activating
      a nuclear receptor, PPARgamma. Therefore, these drugs are often referred to as
      'insulin sensitisers'. Rosiglitazone is the second compound of this group.
      Clinical studies with rosiglitazone have shown that it is effective in lowering
      blood glucose levels in Type 2 diabetic patients treated with either diet alone,
      sulphonylurea or metformin. Preliminary studies suggest that rosiglitazone also
      improves glycaemic control in insulin-treated patients while even slightly
      decreasing insulin dose. The magnitude of the effects is, however, moderate. In
      diet-treated patients, the reduction of HbA1c levels amounted on average 0.5 -
      1.5% and addition to existing sulphonylurea therapy decreased HbA1c by 1.0 -
      1.2%. The clinical relevance of additional beneficial effects, i.e., on blood
      pressure and microalbuminuria, needs to be determined further. Rosiglitazone does
      not cause hypoglycaemia or gastrointestinal side effects. There is however some
      concern related to fluid retention, which seems to be an effect of all PPARgamma
      agonists. In patients treated with rosiglitazone, no severe hepatotoxic side
      effects have been noticed until now. In the treatment of our patients with Type 2
      diabetes, drugs like rosiglitazone which directly reduce insulin resistance are
      very welcome but more data on its combined use with insulin are needed.
      Additional studies will also explore its long-term effects in sparing beta-cell
      function and reducing diabetes-related complications and atherosclerosis.

PMID- 11336600
TI  - Amifostine: chemotherapeutic and radiotherapeutic protective effects.
AB  - Amifostine (Ethyoltrade mark, Alza Pharmaceuticals) is an inorganic thiophosphate
      cytoprotective agent known chemically as ethanethiol, 2-[3-
      aminopropyl)amino]dihydrogen phosphate. It is a prodrug of free thiol (WR-1065)
      that may act as a scavenger of free radicals generated in tissues exposed to
      cytotoxic drugs and binds to reactive metabolites of such drugs. Amifostine was
      originally developed as a radioprotective agent in a classified nuclear warfare
      project. Following declassification of the project it was evaluated as a
      cytoprotective agent against toxicity of the alkylating drugs and cisplatin.
      Differences in the alkaline phosphatase concentration of normal versus tumour
      tissues can result in greater conversion of amifostine in normal tissues. Inside
      the cell, WR-1065 provides an alternative target to DNA and RNA for the reactive
      molecules of alkylating or platinum agents and acts as a potent scavenger of the
      oxygen free radicals induced by ionizing radiation and some chemotherapy agents.
      Preclinical animal studies have demonstrated that the administration of
      amifostine protects against a variety of chemotherapy-related toxicities
      including cisplatin-induced nephrotoxicity, cisplatin-induced neurotoxicity,
      cyclophosphamide- and bleomycin-induced pulmonary toxicity and the cytotoxicities
      (including cardiotoxicity) induced by doxorubicin and related chemotherapeutic
      agents. Amifostine has been shown to protect a variety of animal species from
      lethal doses of radiation. Amifostine gives haematological protection from
      cyclophosphamide, carboplatin, mitomycin C, fotemustine and radiotherapy; renal
      and peripheral nerve protection from cisplatin; mucosa, skin and salivary gland
      protection from radiotherapy. Multiple Phase I studies were carried out with
      amifostine in combination with chemotherapy for various neoplasms. Appropriate
      doses of amifostine were found to be 740 - 910 mg/m(2) in single-dose regimens
      and 340 mg/m(2) in multiple-dose regimens. In radioprotection, doses are
      generally 200 - 350 mg/m(2). For all these characteristics, amifostine has been
      recently approved and suggested in ASCO clinical practice guidelines as a
      radioprotector for head and neck cancer treatment and supportive agent during
      cisplatin-based chemotherapy, in lymphomas and solid tumours. Moreover, its
      spectrum of possible applications is enlarging. As data have been provided
      indicating that amifostine stimulates haematopoiesis, it has been employed with
      intriguing results in the treatment of myelodysplastic syndromes (MDS).

PMID- 11336601
TI  - Topoisomerase I inhibition with topotecan: pharmacologic and clinical issues.
AB  - Topoisomerase I (topo-I) inhibitors are a new class of anticancer agents with a
      mechanism of action aimed at interrupting DNA replication in cancer cells, the
      result of which is cell death. Most, if not all, topo-I inhibitors are
      derivatives of the plant extract camptothecin. Topotecan is a derivative of
      camptothecin which has been structurally modified to increase water solubility.
      The pharmacokinetic profile of topotecan is usually characterised by a two
      compartment model and is linear in the dose range of 0.5 - 3.5 mg/m(2). Current
      clinical trials suggest antitumour activity against a variety of human tumour
      types, including ovarian cancer, non-small cell lung cancer (NSCLC) and non
      lymphocytic haematologic malignancies. The main dose-limiting toxicity (DLT) is
      non-cumulative myelosuppression. Non-haematologic toxicities are usually mild.
      Based on several Phase I studies, the recommended Phase II dose was 1.5
      mg/m(2)/day iv. for 5 days. Current Phase I and Phase II trials are evaluating
      the combination of topotecan with other chemotherapeutic agents to increase the
      therapeutic benefits of topotecan. The DLT in these trials is mainly
      myelosuppression.

PMID- 11336602
TI  - Paediatric psychopharmacology: closing the gap between science and practice.
AB  - Children and adolescents do not always respond to treatment with psychotropic
      agents in a similar fashion to adults. Differences in safety and therapeutic
      response may occur across the life cycle. For example, despite the fact that
      tricyclic antidepressants are traditionally the 'gold standards' of
      pharmacotherapy for depressed adults, it does not seem that youths with
      depression benefit from treatment with these agents [1]. Similarly, it appears
      that earlier age at onset is associated with a reduced propensity to respond to
      neuroleptics for patients with schizophrenia [2]. In addition, young patients
      have been noted to be at higher risk for developing neuroleptic-induced
      extrapyramidal side effects when compared to adults [3]. Simply put, what is
      known about the safety and effectiveness of psychotropic compounds in adults
      cannot necessarily be presumed to be applicable to teenagers or children.

PMID- 11336603
TI  - Sex hormones and their impact on dementia and depression: a clinical perspective.
AB  - Sex hormones have often been associated with changes in behavioural and mental
      abilities. This paper reviews the scientific literature published between 1990
      and 2000 investigating the effects of oestrogen, testosterone and
      dehydroepiandrosterone (DHEA) on depression and dementia. Oestrogen seems to have
      a positive effect in preventing, but not treating, Alzheimer's disease. Oestrogen
      use may also improve mood amongst women with postnatal or perimenopausal
      depression; however, it may contribute to increasing depressive symptoms in women
      with premenstrual dysphoria. The behavioural effects of testosterone and DHEA
      remain unclear but the results of preliminary reports suggest that their use is
      associated with improved mood. At present, there is not enough hard data to
      support the use of sex hormones and DHEA for the treatment of depression or
      memory deficits.

PMID- 11336604
TI  - Applications of pharmacogenetics in psychiatry: personalisation of treatment.
AB  - In spite of the lack of epidemiological information, pharmacogenetic research has
      produced evidence of the relationship between genes and treatment response.
      Genetic variants of metabolic enzymes are related to toxic reactions;
      polymorphisms in genes coding for drug-targeted neurotransmitter receptors
      influence therapeutic efficacy. Also, recent studies have shown that response to
      antipsychotic drugs can be predicted by looking at the individual's
      pharmacogenetic profile. In addition to providing the first evidence that
      treatment response can be predicted by looking at a core of key genes, these
      studies illustrate the feasibility of individualisation of psychiatric treatment.

PMID- 11336605
TI  - Antipsychotic drug use in neurodegenerative disease in the elderly: problems and
      potential from a pharmacological perspective.
AB  - The past decade has seen the introduction of several new antipsychotics for the
      treatment of schizophrenia. These drugs demonstrate substantially lower levels of
      extrapyramidal side effects (EPS) than the classical antipsychotics, as well as
      having (often poorly supported) claims of increased efficacy at ameliorating
      certain schizophrenic syndromes. Increasingly, these 'atypical' drugs are being
      used in the treatment of psychotic or related behavioural disturbances in
      patients with neurodegenerative disease. Thus, some newer antipsychotics are
      particularly valuable in ameliorating the L-dopa-induced psychosis in Parkinson's
      disease, while behavioural problems in dementing disorders, such as those
      occurring in Alzheimer's disease, are also frequently treated by antipsychotic
      drugs. The relationship between drug pharmacology and neurotransmitter pathology
      is essential to understanding the relative efficacy of individual antipsychotic
      drugs in treating the psychotic and behavioural disturbances of neurodegenerative
      disorders.

PMID- 11336606
TI  - Treatment of status migrainosus.
AB  - Migraine episodes that persist for at least 3 days despite treatment are termed
      status migrainosus. Traditionally, these long-lasting migraine episodes were
      treated with brief in-patient hospitalisations for iv. medication. The full
      duration of disability associated with these episodes includes both the several
      days of migraine and the several days of hospital stay. The development of
      medications that specifically target the mechanism of migraine, such as
      dihydroergotamine and the triptans, has reduced the number of headache episodes
      that persist after initial treatment or fail to respond to self-administered
      therapy.

PMID- 11336607
TI  - Non-dopaminergic drug treatment of Parkinson's disease.
AB  - Several lines of evidence suggest that substitution of the dopaminergic striatal
      deficit only represents one important aspect of the treatment of Parkinson's
      disease (PD) because neurotransmitter systems other than the dopaminergic one
      also degenerate and aggravate parkinsonian motor, vegetative and cognitive
      symptoms. Thus, regulation and balance of altered non-dopaminergic
      neurotransmission could provide an additional benefit for parkinsonian patients
      (PP). Moreover, onset of motor complications, psychosis and loss of drug efficacy
      increasingly reduce parkinsonian quality of life in the course of long-term
      dopamine substitution. Indirect stimulation of the dopaminergic neurotransmission
      via non-dopaminergic systems is an upcoming interesting strategy to solve these
      problems. Treatment of L-dopa-associated dyskinesias represents a further
      important future task of non-dopaminergic drug therapy. NMDA antagonists are a
      promising therapeutic option but further trials are necessary to elucidate their
      efficacy. A further peripheral effect of L-dopa/dopa decarboxylase inhibitor
      (DDI) application is increased homocysteine synthesis with its putative
      hypothetical additional central impact on neurodegeneration and progression of
      PD. Long-term monitoring with subsequent therapeutic decrease of homocysteine
      levels with folic acid could result in substantial clinical benefits at
      reasonable costs for PP. Also, it could hypothetically influence altered
      dopaminergic and non-dopaminergic neurotransmission beside its impact on
      occurrence of vascular disease and altered striatal microvascularisation in PD.
      The interesting field of non-dopaminergic drug therapy is emerging and will
      hopefully lead to a better understanding of PD and subsequently improve drug
      therapy of parkinsonian symptoms, which do not respond to dopaminergic
      substitution or are long-term complications of dopamine substitution.

PMID- 11336608
TI  - Present and future pharmacotherapeutic options for adult attention
      deficit/hyperactivity disorder.
AB  - Attention deficit/hyperactivity disorder (ADHD) is often a lifelong condition.
      When untreated or undertreated, it appears to have a deleterious impact upon the
      daily functioning of the majority of adults that were diagnosed with this
      condition during childhood. Effective treatment, under the best circumstances, is
      multi-modal. The recent MTA study staged by the United States government
      confirmed the primary role of psychostimulants for children with this condition.
      The findings from this study have been generalised to adults that also have ADHD,
      particularly in cases where there is a well-defined longitudinal history dating
      back to early childhood. Psychostimulants remain a viable first-choice strategy
      for adults with ADHD. There are idiosyncratic differences in response to the
      various psychostimulants for any given individual with ADHD. Furthermore, the
      emergence of long-acting, once daily psychostimulant medications is likely to
      improve the calibre of care for adults with ADHD. A number of alternative
      pharmacotherapies have been studied, or are being developed, for adults with
      ADHD. These pharmacotherapies include antidepressant medications that affect
      dopaminergic and noradrenergic bioavailability, as well as cholinergic agents. In
      addition, agents that manipulate histaminergic and glutaminergic receptors are
      being studied as possible non-stimulant alternatives in the management of adult
      ADHD. More information is needed before any definitive statements can be made
      concerning the feasibility and utility of these non-stimulant medication
      approaches.

PMID- 11336609
TI  - Pharmacotherapeutic management of autism.
AB  - There are no medications that are specifically marketed for the treatment of
      autism. There does exist, however, an extensive body of literature describing
      both open-label and controlled studies of medications in the treatment of both
      children and adults with autism. Some of the better-studied medications
      (including haloperidol and risperidone) are often efficacious in treating
      associated symptoms of autism but can also cause unacceptable adverse effects.
      Early studies of serotonin re-uptake inhibitors appear promising but may not be
      indicated for all age groups. Small, controlled studies of methylphenidate and
      clonidine indicate a possible role for these medications in the treatment of
      hyperactivity in autism. No medications have been proven to be efficacious in the
      treatment of the core social or communication impairment seen in autism. Current
      pharmacological management is best aimed at target symptoms that have been
      demonstrated to respond to medication in treatment studies.

PMID- 11336610
TI  - Bipolar disorders: new approaches to therapy.
AB  - This article reviews the evidence supporting different somatic treatment
      strategies in the acute and maintenance treatment phases of bipolar disorder.
      Bipolar affective disorder is a chronic disorder with a life time incidence of
      0.3 - 1.5/100 [1]. Severe affective disorder is associated with a risk of
      completed suicide of 6 - 15% [2,3]. Traditionally, bipolar disorder has been
      considered as an episodic disorder with good inter-episode recovery [4]. This is
      being increasingly challenged with patients demonstrating social, marital,
      occupational and cognitive dysfunction, even when euthymic [5]. The management of
      bipolar disorder should be considered in the context of; the type of episode,
      this may be manic, depressed or mixed; the degree and rate of recovery; the
      cycling frequency and precipitant, if any, for recurrence and the onset and
      evolution of the underlying illness. On average, four episodes occur every 10
      years. However 13 - 24% of patients develop rapid cycling disorder, in which four
      or more episodes occur within a year. Patients with bipolar disorder often have
      co-morbid anxiety and substance abuse. Moreover, axis I co-morbidity may be
      associated with an earlier age at onset and worsening course of bipolar illness.
      [6]. Axis II co-morbidity is also common, this was highlighted in a study by Kay
      and colleagues who, after excluding patients with a history of alcohol misuse,
      demonstrated axis II co-morbidity in almost a quarter of euthymic bipolar
      patients [7]. Good practice relies on an overall management plan that
      incorporates somatic, psychological and social approaches. This paper will focus
      on one element of such a plan, the currently available somatic management
      strategies for bipolar disorder.

PMID- 11336611
TI  - Special issues in the treatment of paediatric bipolar disorder.
AB  - Paediatric bipolar disorder (PBD) is an increasingly diagnosed disorder affecting
      an estimated 1% of children and adolescents. Pharmacological treatment studies in
      PBD have lagged far behind those in adults. Children are currently treated with
      pharmacological agents, most of which have proven efficacy in adults. However,
      PBD is distinct from adult forms of bipolar disorder (BD) and may present unique
      treatment challenges. PBD often presents with rapid cycling and mixed manic
      states and a high co-morbidity with behavioural and attention disorders. Early
      onset depression may also be an early sign of PBD. Due to developmental
      considerations, the diagnosis of BD may be difficult to make in children without
      semi-structured interviews. This report discusses the special issues that should
      be considered when treating PBD and reviews the current literature regarding
      pharmacotherapy of this population. Mood stabilisers have been studied mostly in
      an open, uncontrolled fashion but there is growing evidence that lithium,
      divalproex and carbamazepine are effective in treating PBD. More recent treatment
      options include atypical antipsychotics and newer anticonvulsants. Other novel
      agents are currently being investigated in adult BD and may prove applicable to
      the paediatric form. Finally, based on the available data, a treatment algorithm
      for PBD is proposed.

PMID- 11336612
TI  - Immunomodulatory drugs for multiple sclerosis: a systematic review of clinical
      and cost effectiveness.
AB  - Uncertainties about the clinical and cost effectiveness of immunomodulatory drugs
      for multiple sclerosis (MS), as well as concerns about funding treatment,
      continue to influence their use. The National Institute for Clinical Excellence
      (NICE) in England and Wales has been appraising the evidence on the clinical and
      cost effectiveness of IFN-beta and glatiramer to provide guidance to the NHS. It
      has proved a difficult task. This paper is an update of our systematic review
      which assesses the evidence on the clinical and cost effectiveness of a range of
      immunomodulatory drugs for MS, including azathioprine, IFN-beta, cladribine,
      cyclophosphamide, glatiramer, intravenous immunoglobulin (IVIg), methotrexate and
      mitoxantrone. Searches of electronic databases (such as Medline, Embase and the
      Cochrane Library) and bibliographies of related papers, as well as consultation
      with experts, for systematic reviews of randomised controlled trials (RCTs) and
      direct reports of RCTs revealed 26 studies of clinical effectiveness and eight
      economic evaluations that met the criteria for inclusion. The quality of the
      evidence was often poor, affected by methodological limitations. Evidence on the
      clinical effectiveness of immunomodulatory drugs showed some clinical effect,
      with reductions in relapse rates and/or progression to disability for people with
      MS. However, benefits from these drugs may be lessened by side effects.
      Assessment of cost effectiveness was limited to IFN-beta and glatiramer, showing
      that any benefit from these drugs was achieved at very high cost. The
      inadequacies in the evidence of clinical and cost effectiveness on some
      immunomodulatory drugs for the treatment of people with MS necessitate further
      rigorous RCTs and comparative economic evaluations of different alternatives.

PMID- 11336613
TI  - Assessing the economic impact of psychiatric disorders: where to begin?
AB  - Over the past decade, psychiatric disorders have increasingly been regarded as
      serious public health concerns, with debilitating symptoms as well as high social
      and economic costs to patients, caregivers, third party payers and society. In
      this article, we review findings from recent research on psychiatric disorders,
      while providing a framework for assessing their pharmacoeconomic impact. In
      particular, we consider the prevalence of psychiatric disorders, their far
      reaching impacts, and their associated treatment patterns. These categories
      present a starting point for analysing the pharmacoeconomic consequences of
      psychiatric disorders and underlie an expert opinion in this context

PMID- 11336614
TI  - Review of rivastigmine and its clinical applications in Alzheimer's disease and
      related disorders.
AB  - Rivastigmine (Exelontrade mark, Novartis) is a novel intermediate-acting
      reversible and non-competitive carbamate acetylcholinesterase (AChE) that was
      recently introduced for the treatment of Alzheimer's disease (AD). Preclinical
      studies have shown that rivastigmine has many similarities to other currently
      available cholinesterase inhibitors (ChEIs) and some important differences. The
      drug has been evaluated for this use in two well designed, published, adequately
      powered, Phase III, 26 week clinical trials that included a total of more than
      1500 rivastigmine and 700 placebo recipients. Most of these patients had
      concomitant disorders that were being treated with numerous other drugs. These
      studies indicate that rivastigmine (6 - 12 mg/day) usually produces cognitive,
      global and functional changes that indicate significantly less deterioration than
      was observed with placebo in patients with mild-to-moderate AD, with higher doses
      producing more benefits. Rivastigmine is beneficial in all three domains (namely
      cognition, daily activities and behaviour) of AD. Data on long-term efficacy
      support continued benefits of rivastigmine beyond 6 months. Rivastigmine is
      generally well-tolerated with no requirement for routine electrocardiogram (ECG)
      or blood monitoring. Rivastigmine causes adverse events that are generally those
      expected from a ChEI and mainly involve gastrointestinal system. They are usually
      mild-to-moderate, of short duration and responsive to dosage reduction. They
      occur mostly during the dosage titration phase and decrease during the
      maintenance phase. Clinically significant drug-drug interactions are unlikely.
      The consistent efficacy in treating all three domains (cognition, daily
      functioning and behaviour) and good tolerability, particularly with slow
      titration, makes rivastigmine a good first-line ChEI therapy for the treatment of
      AD. Therapeutic dose range is 6 - 12 mg/day. Rivastigmine should be started at
      1.5 mg b.i.d. with meals and increased at 2 - 4 week intervals to achieve the
      highest tolerated dose.

PMID- 11336615
TI  - Use of olanzapine in non-psychotic psychiatric disorders.
AB  - The history of antipsychotic medications begins in the 1950s with chlorpromazine,
      developed originally as an antihistamine but found to be an aid in the reduction
      of symptoms of delusions and hallucinations. This phenothiazine derivative was
      followed by numerous others in the same class (e.g., thioridazine) and then by
      antipsychotics in other classes (e.g., the popular haloperidol of the
      butyrophenone class). This group of medications is associated with a number of
      unpleasant side effects and complications. These included extrapyramidal symptoms
      (EPS), orthostatic hypotension, hyperprolactinemia and last, but certainly not
      least, tardive dyskinesia (TD). As a consequence, other alternative
      antipsychotics were developed in which D(2) blockade effect generally associated
      with EPS and TD was offset by 5-HT(2) antagonism. The first of this class was
      clozapine; however, it is associated with agranulocytopenia of sudden onset as
      well as seizure induction. However, olanzapine, a close structural relative, was
      soon synthesised for treatment of psychosis and particularly schizophrenia
      (Zyprexatrade mark, Eli Lilly). It was released in the US in November 1996 with
      FDA approval for that indication. However, antipsychotics have always been used
      for other psychiatric disorders, aside from schizophrenia. This includes, in
      particular, mania, where chlorpromazine use predated lithium as an effective
      treatment. Other uses for antipsychotics have included other mood disorders,
      dementia, childhood disorders and personality problems. Here, information on the
      application of olanzapine to non-schizophrenic disorders is reviewed. Despite the
      fact that the research post-dates FDA approval in 1996, there was already
      sufficient evidence for olanzapine's effectiveness in acute mania to obtain
      approval from the US FDA in March 2000. Other research supports its use as
      adjunctive therapy in depressive disorders. Phase IV studies and case reports
      have found limited support for olanzapine's use in a variety of other psychiatric
      disorders, behavioural disorders of dementia (including Alzheimer's disease),
      pervasive developmental disorder of childhood, obsessive-compulsive disorder and
      borderline personality disorder. In each of these latter diagnoses, double-blind
      studies are either underway or are planned to establish efficacy.

PMID- 11336616
TI  - Citalopram: a comprehensive review.
AB  - Citalopram is a selective serotonin re-uptake inhibitor that has demonstrated
      antidepressant efficacy in numerous controlled clinical trials. Additional
      studies have shown that the drug benefits patients with other illnesses that are
      related in some way to serotonergic dysfunction, including anxiety, panic
      disorder, obsessive-compulsive disorder, premenstrual dysphoria, alcohol
      dependence and the behavioural disturbances of dementia. This paper reviews the
      full spectrum of citalopram's clinical efficacy, as well as its safety and
      tolerability, in a range of patients.

PMID- 11336617
TI  - Clinical review of glimepiride.
AB  - This article reviews the pharmacological and clinical aspects of glimepiride, the
      latest second-generation sulfonylurea for treatment of Type 2 diabetes mellitus
      (DM). Glimepiride therapy ameliorates the relative insulin secretory deficit
      found in most patients with Type 2 DM. It is a direct insulin secretagogue;
      indirectly, it also increases insulin secretion in response to fuels such as
      glucose. Its action to augment insulin secretion requires binding to a high
      affinity sulfonylurea receptor, which results in closure of ATP-sensitive
      potassium channels in the beta-cells of the pancreas. The question has been
      raised whether insulin secretagogues by acting on vascular or myocardial
      potassium channels may prevent ischaemic preconditioning, a physiological
      adaptation that could affect the outcome of coronary heart disease, but there is
      evidence against this concern being applicable to glimepiride. Glimepiride's
      antihyperglycaemic efficacy is equal to other secretagogues. It has
      pharmacokinetic properties that make it less prone to cause hypoglycaemia in
      renal dysfunction than some other insulin secretagogues, particularly glyburide
      (also known as glibenclamide in Europe). Its convenient once daily dosing may
      enhance compliance for diabetic patients who often also require medications for
      other co-morbid conditions, such as hypertension, hyperlipidaemia and cardiac
      disease. Glimepiride is approved for monotherapy, for combination with metformin
      and with insulin. Clinically, its reduced risk of hypoglycaemia makes it
      preferable to some other insulin secretagogues when attempting to achieve
      recommended glycaemic control (haemoglobin A(1c) (HgbA(1c)) 7%). Using suppertime
      neutral protamine Hagedorn (NPH) and regular insulin with morning glimepiride in
      overweight diabetic patients achieves glycaemic goals more quickly than insulin
      alone and with lower insulin doses.

PMID- 11336618
TI  - The current status of antihypertensive treatments: into the new millennium.
AB  - In this short review, we present a historical perspective of the treatment of
      hypertension, highlight some current issues and look to the possible future of
      antihypertensive therapy. The distribution of blood pressure within the
      population adopts a continuous, albeit somewhat skewed, distribution, so what
      constitutes hypertension? Conventionally, the disease has been defined as a level
      of blood pressure >> 140/90 mmHg. Accepting this 'arbitrary' definition infers
      that approximately one quarter of the adult population in the US are hypertensive
      [1]. This has significant implications in terms of the impact upon public health.
      We know that treatment of hypertension can prevent the serious consequences of
      cardiovascular disease: stroke, myocardial infarction (MI), heart failure and
      renal disease. Thus, it is important that raised blood pressure is both detected
      and effectively lowered. To what level should blood pressure be reduced.
      Conventionally, a level of 120/80 mmHg has been used to define normotension but
      there are indications that under certain circumstances this should not be the
      target. The question also arises as to whether it matters how blood pressure is
      treated. The choice of agent may ultimately depend upon the presence of any
      concomitant condition and risk factors. Recent trial evidence has concluded that
      therapy selected to treat raised blood pressure should take into account the
      overall cardiovascular risk profile of the patient [2].

PMID- 11336619
TI  - Cardioprotection: emerging pharmacotherapy.
AB  - By the year 2020, it is predicted that acute coronary occlusion will be the major
      cause of death in the world. Recent advances in reperfusion therapy have
      substantially improved survival of patients with acute coronary syndromes. While
      early reperfusion reduces mortality, a time limitation exists with regard to
      myocardial salvage. In fact, the major limiting factor in further improving
      survival of patients with myocardial ischaemia is the susceptibility of the
      cardiomyocyte to ischaemic insult and lethal cell injury. Over the last decade
      substantial progress has been made in our understanding of the fundamental
      mechanisms of ischaemia/reperfusion injury. From this work novel means which
      limit or delay myocyte death have emerged and are currently under development as
      therapeutic candidates for the management of acute coronary syndromes. This
      report examines cardioprotective mechanisms and reviews clinical evidence for
      myocardial protective therapies.

PMID- 11336620
TI  - Current approaches to therapy for vascular injury.
AB  - Vascular injury is a ubiquitous phenomenon which can be both occult (such as with
      hyperlipidemia) and overt (such as with angioplasty). While the exact
      pathophysiology differs between acute and chronic atherosclerosis, both lesions
      can be mechanistically explained by the vasculature's exaggerated response to
      injury. Pharmacological attempts to treat atherosclerotic cardiovascular disease
      can be categorised by their role in modifying this inflammatory response. This
      manuscript reviews current therapy for cardiovascular injury at two levels: the
      chronic smouldering atheromatous lesion and intimal hyperplasia associated with
      acute vascular intervention. In addition, future therapeutic strategies, based
      within this inflammatory paradigm, are discussed.

PMID- 11336621
TI  - Emerging concepts in disease management: a role for antimicrobial therapy in
      coronary artery disease.
AB  - Coronary artery disease, the leading cause of morbidity and mortality in
      developed countries, is a chronic inflammatory process that develops in response
      to a variety of injuries. A number of microbial organisms have been implicated in
      its pathogenesis. The strongest evidence to date for an association between an
      infectious agent and coronary heart disease is that for Chlamydia pneumoniae.
      Evidence implicating other microbial organisms is much less compelling. Sero
      epidemiological and pathological data have linked infection with C. pneumoniae to
      atherosclerotic coronary artery disease. A possible mechanism by which C.
      pneumoniae may participate in the pathogenesis of atherosclerosis is through
      immune activation and the initiation of a chronic inflammatory state in the
      infected arterial wall. Locally secreted inflammatory cytokines trigger a cascade
      of secondary cellular processes that lead to characteristic structural changes.
      C. pneumoniae has been detected in atherosclerotic plaques and in the serum of
      patients with coronary artery disease. It induces foam cells (the hallmark of
      early atherosclerosis) and it markedly accelerates this disease process in animal
      models. C. pneumoniae has been associated with elevated levels of inflammatory
      cytokines and acute phase reactants. Data from three interventional studies in
      humans have suggested that treatment with antibiotics decreases inflammatory
      markers and perhaps influences the anti-C. pneumoniae antibody titers; however,
      adverse clinical events were not uniformly reduced in all trials. Two large
      prospective clinical trials, the WIZARD trial and ACES, are underway to confirm
      these preliminary findings and test the hypothesis that antibiotics may be
      beneficial in preventing or modifying the course of coronary artery disease. At
      present, antimicrobial therapy for atherosclerosis is not advocated outside of
      well-controlled research settings.

PMID- 11336622
TI  - Congenital long QT syndromes and Brugada syndrome: the arrhythmogenic ion channel
      disorders.
AB  - Congenital long QT syndromes (LQTS) and Brugada syndrome are hereditary disorders
      of cardiac ion channels which result in life-threatening cardiac arrhythmias or
      sudden cardiac death in patients with anatomically normal hearts. The
      pathogenesis of these dramatic events has been partially elucidated with the
      identification of the individual ion channels involved and understanding of the
      effect of some disease-causing mutations on the membrane currents and action
      potential. The clinical spectrum of congenital LQTS is broader than previously
      thought and involves certain patients previously diagnosed with idiosyncratic
      drug-induced proarrhythmia. The initial treatment for congenital LQTS patients
      involves beta-blockers in most cases. Indications for implantable cardioverter
      defibrillator (ICD) or pace-maker (PM) implantation in selected individuals
      continue to evolve.

PMID- 11336623
TI  - The pathophysiological role of prostaglandins in penile erection.
AB  - Penile erection is a complex haemodynamic event and relaxation of the vascular
      smooth muscle of the penis is fundamental to this process. This is primarily
      mediated by nitric oxide (NO) produced from non-adrenergic non-cholinergic (NANC)
      nerves and the endothelium surrounding the corporal sinusoids. However, corporal
      tissue has been shown to produce a number of other vasoactive factors, including
      prostaglandins (PGs), which appear to not only have diverse physiological
      effects, but are also able to modulate the effects of other neurotransmitters,
      including NO.

PMID- 11336624
TI  - Bacterial resistance in urinary tract infections: how to stem the tide.
AB  - Each year, approximately 10% of the population is diagnosed with a urinary tract
      infection (UTI). Escherichia coli is the most prevalent pathogen in UTIs but
      other species make significant contributions. UTIs are commonly treated with
      antibiotics and, therefore, a potential source for the emergence and/or selection
      of resistant bacteria. Although susceptibility to some antibiotics for a number
      of species is still high, resistance is an issue both for community- and hospital
      acquired UTI. However, often treatment is empiric, especially in the community
      setting. This empiric treatment is often guided by inadequate information about
      the (local) rates of resistance, selection and emergence of resistance, although
      there is a general consensus that there is a relationship between antibiotic use
      and resistance. It is well known that some antibiotics, e.g., some
      fluoroquinolones, are able to induce mutations leading to resistance but the
      antibiotics prescribed also affect the commensal flora, potentially selecting
      resistant organisms. However, antibiotics meant to treat other infections may
      select uropathogens and, thereby, the risk for UTIs increases. The duration of
      treatment of any infection is an important factor to consider in this respect, as
      well as subinhibitory concentrations of the antibiotic prescribed. Prudent use of
      new and still effective antibiotics is required. Although prudent use of these
      antibiotics may help to reduce the prevalence of antibiotic-resistant
      uropathogens, elimination will be hard to achieve. Therefore, we believe, that we
      can reduce the tide but we will still have to deal with the resistance problem in
      the future.

PMID- 11336625
TI  - Atorvastatin.
AB  - Atorvastatin (Lipitor, Pfizer) is a safe and effective 3-hydroxy-3-methyl
      glutaryl-CoA (HMG-CoA) reductase inhibitor (statin). It is the most potent
      currently available statin in terms of lowering low-density lipoprotein (LDL) and
      total cholesterol levels. It was the first statin shown to lower triglycerides in
      patients with isolated hypertriglyceridaemia. It has a good safety profile. In
      common with other statins, it has non-lipid-lowering effects including improving
      endothelial function, antiproliferative actions on smooth muscle and reducing
      platelet aggregation. It also has anti-inflammatory effects and may reduce plasma
      glucose levels. Clinical trial evidence with this statin is currently limited. It
      did slightly reduce events in the AVERT trial comparing patients receiving
      coronary angioplasty with those receiving high-dose atorvastatin therapy and in
      the MIRACL study reduced ischemia in patients with acute coronary syndromes.
      Other end point trials are in progress.

PMID- 11336626
TI  - Carvedilol in the treatment of chronic heart failure.
AB  - Along with the angiotensin-converting enzyme inhibitors (ACEIs), the beta
      adrenergic receptor blockers have gradually emerged to be standard in the therapy
      of heart failure. Individual beta-blockers that have been shown to reduce all
      cause mortality in patients with heart failure include bisoprolol, metoprolol and
      carvedilol. Carvedilol distinguishes from the other beta-blockers as being a non
      selective beta(1)- and beta(2)-receptor blocker with (1)-receptor blockade effect
      and anti-oxidant properties. The drug does not have sympathomimetic activity and
      has vasodilatory effects attributable to its (1)-receptor blockade property.
      Experimental and clinical studies have confirmed carvedilol's vasodilator, anti
      oxidant and anti-apoptotic properties, which may contribute to its effect in
      reversing cardiac remodelling in animal models and patients with heart failure.
      These pharmacological properties render carvedilol a potentially useful agent in
      the treatment of patients with heart failure. Early studies of carvedilol in
      heart failure have reported beneficial haemodynamic effects but variable effects
      on exercise tolerance and clinical well being. The large-scale US Carvedilol
      Heart Failure Program and the Australian/New Zealand Heart Failure Collaborative
      Research Group reported beneficial effects of carvedilol on mortality, morbidity
      and clinical well being in patients with mild-to-moderate heart failure. The
      recently reported but yet unpublished preliminary results of the COPERNICUS study
      suggest that carvedilol improves mortality and morbidity in patients with
      advanced heart failure and severe symptoms. At this time, it is unclear whether
      the ancillary pharmacological properties of carvedilol can be translated to more
      superior clinical benefit compared to the other beta-blockers. Preliminary
      studies examining surrogate end points suggest that carvedilol may improve left
      ventricular ejection fraction (LVEF) more than metoprolol. More conclusive
      information regarding their relative effects of clinical outcomes will await the
      completion of the COMET study, which compares the effect of metoprolol and
      carvedilol on mortality and morbidity, expected at the end of the year 2002.

PMID- 11336627
TI  - The role of nicorandil in the treatment of myocardial ischaemia.
AB  - Nicorandil is an anti-anginal agent that has been used in the United Kingdom for
      over 6 years and is becoming increasingly popular. It induces coronary and
      peripheral vasodilatation via a dualistic mode of action, mediated by the opening
      of potassium-ATP channels (K(ATP)) and its nitrate effect by stimulation of
      adenyl cyclase, with an increase in cGMP levels. Comparison to nitrates and other
      anti-anginal agents have shown it to be of equal efficacy in relieving ischaemic
      symptoms. Recent evidence suggests a role for nicorandil as a myocardial
      preconditioning agent but this may be limited by systemic vasodilatation. There
      is ongoing research into its role in improving the long-term outcome of patients
      with ischaemic heart disease (IHD). It has been shown to be of proven efficacy in
      the treatment of IHD and further research will clarify other uses of this agent.

PMID- 11336628
TI  - Trimetazidine for stable angina pectoris.
AB  - Stable angina pectoris, a symptom of coronary heart disease (CHD), manifests as
      stress-induced ischaemic episodes resulting in severe chest pain. Therapeutic
      aims are to improve quality of life by decreasing anginal attacks and to prevent
      myocardial infarction (MI) and death. Current anginal medications include beta
      blockers and calcium antagonists, which decrease ischaemic severity by reducing
      cardiac workload, and nitrates, which increase coronary blood flow. A new
      therapeutic approach is the use of metabolic agents, such as trimetazidine, which
      are cytoprotective during ischaemia. Results of several clinical trials
      demonstrated that trimetazidine, at the standard dose of 20 mg t.i.d., increased
      exercise capacity, decreased anginal incidence and decreased left-ventricular
      (LV) dysfunction compared to placebo. Trimetazidine was also as effective as
      propranolol (120 - 160 mg/day) and nifedipine (40 mg/day) in decreasing anginal
      episodes and improving exercise parameters. Trimetazidine improved anginal
      frequency and symptoms in patients in which treatment with diltiazem, nifedipine,
      propranolol, pindolol, oxprenolol or long-acting nitrates had failed.
      Trimetazidine was also more effective than isosorbide dinitrate (30 mg/day) as an
      adjunct to propranolol. Despite efficacy being equivalent to that of beta
      blockers and calcium antagonists, trimetazidine does not depress cardiac function
      and, correspondingly, is not contraindicated in any condition. Adverse effects of
      trimetazidine are mild and infrequent. In summary, clinical data indicate that
      trimetazidine is a safe, effective treatment for the symptoms of stable angina
      pectoris when used either as a monotherapy or an adjunctive therapy. Longer-term
      trials are necessary to determine whether trimetazidine will be effective in
      reducing rates of mortality and MI.

PMID- 11336629
TI  - Review of sertraline and its clinical applications in psychiatric disorders.
AB  - Sertraline (Zoloft, Pfizer) has been shown in numerous controlled studies to have
      similar efficacy to other selective serotonin (5-HT) re-uptake inhibitors (SSRIs)
      in the treatment of depression and anxiety disorders. Further research is
      indicating that the efficacy of sertraline extends even beyond the treatment of
      depression and anxiety to include utility in eating disorders, premenstrual
      dysphoric disorder (PMDD) and possibly substance abuse treatment. Along with
      other SSRIs, sertraline offers several advantages over older antidepressants,
      including improved patient tolerability, low risk of lethality in overdose and no
      dependence potential. In head-to-head comparisons, sertraline appears to be at
      least as well-tolerated as other SSRIs and may even have a more favourable side
      effect profile. Low potential for pharmacokinetic drug interactions is another
      advantage of sertraline. Unlike fluoxetine, fluvoxamine and paroxetine,
      sertraline is not a potent inhibitor of any of the cytochrome P450 isoenzyme
      systems. As a result of its proven efficacy, good tolerability and lack of
      pharmacokinetic interactions, sertraline should be considered first-line in the
      treatment of anxiety and depressive disorders.

PMID- 11336631
TI  - Arg-Tyr-Asp (RYD) and Arg-Cys-Asp (RCD) motifs in dendroaspin promote selective
      inhibition of beta1 and beta3 integrins.
AB  - Arg-Gly-Asp (RGD) is a unique minimal integrin-binding sequence that is found
      within several glycoprotein ligands. This sequence has also been found in snake
      venom anti-platelet proteins, including the disintegrins and dendroaspin, a
      natural variant of short-chain neurotoxins isolated from the venom of Dendroaspis
      jamesonii. In the present study, the motifs RYD and RCD were introduced into the
      dendroaspin scaffold to replace RGD. Both motifs in dendroaspin caused inhibition
      of ADP-induced platelet aggregation with IC(50) values of 200 and 300 nM
      respectively, similar to that of the wild-type RGD motif (170 nM). In comparison
      with wild-type dendroaspin, both RYD- and RCD-containing dendroaspins were more
      selective in the inhibition of the adhesion of K562 cells to laminin rather than
      to fibrinogen and fibronectin, even though they were 10-30-fold less potent at
      inhibiting K562 cell (containing alpha(5)beta(1) integrin) adhesion to laminin
      compared with wild-type. Interestingly, the RYD motif produced a similar IC(50)
      value to the RGD motif at inhibiting A375-SM cell (beta(3) integrin) adhesion to
      collagen, whereas the RCD motif was approx. 2-6-fold less potent compared with
      either RGD or RYD. These findings show that the selectivity of dendroaspin
      binding to beta(1) and beta(3) integrins can be modulated by the introduction of
      alternative cell recognition sequences.

PMID- 11336630
TI  - The marks, mechanisms and memory of epigenetic states in mammals.
AB  - It is well recognized that there is a surprising degree of phenotypic variation
      among genetically identical individuals, even when the environmental influences,
      in the strict sense of the word, are identical. Genetic textbooks acknowledge
      this fact and use different terms, such as 'intangible variation' or
      'developmental noise', to describe it. We believe that this intangible variation
      results from the stochastic establishment of epigenetic modifications to the DNA
      nucleotide sequence. These modifications, which may involve cytosine methylation
      and chromatin remodelling, result in alterations in gene expression which, in
      turn, affects the phenotype of the organism. Recent evidence, from our work and
      that of others in mice, suggests that these epigenetic modifications, which in
      the past were thought to be cleared and reset on passage through the germline,
      may sometimes be inherited to the next generation. This is termed epigenetic
      inheritance, and while this process has been well recognized in plants, the
      recent findings in mice force us to consider the implications of this type of
      inheritance in mammals. At this stage we do not know how extensive this
      phenomenon is in humans, but it may well turn out to be the explanation for some
      diseases which appear to be sporadic or show only weak genetic linkage.

PMID- 11336632
TI  - Engineering of a glycosidase Family 7 cellobiohydrolase to more alkaline pH
      optimum: the pH behaviour of Trichoderma reesei Cel7A and its E223S/
      A224H/L225V/T226A/D262G mutant.
AB  - The crystal structures of Family 7 glycohydrolases suggest that a histidine
      residue near the acid/base catalyst could account for the higher pH optimum of
      the Humicola insolens endoglucanase Cel7B, than the corresponding Trichoderma
      reesei enzymes. Modelling studies indicated that introduction of histidine at the
      homologous position in T. reesei Cel7A (Ala(224)) required additional changes to
      accommodate the bulkier histidine side chain. X-ray crystallography of the
      catalytic domain of the E223S/A224H/L225V/T226A/D262G mutant reveals that major
      differences from the wild-type are confined to the mutations themselves. The
      introduced histidine residue is in plane with its counterpart in H. insolens
      Cel7B, but is 1.0 A (=0.1 nm) closer to the acid/base Glu(217) residue, with a
      3.1 A contact between N(epsilon2) and O(epsilon1). The pH variation of
      k(cat)/K(m) for 3,4-dinitrophenyl lactoside hydrolysis was accurately bell-shaped
      for both wild-type and mutant, with pK(1) shifting from 2.22+/-0.03 in the wild
      type to 3.19+/-0.03 in the mutant, and pK(2) shifting from 5.99+/-0.02 to 6.78+/
      0.02. With this poor substrate, the ionizations probably represent those of the
      free enzyme. The relative k(cat) for 2-chloro-4-nitrophenyl lactoside showed
      similar behaviour. The shift in the mutant pH optimum was associated with lower
      k(cat)/K(m) values for both lactosides and cellobiosides, and a marginally lower
      stability. However, k(cat) values for cellobiosides are higher for the mutant.
      This we attribute to reduced non-productive binding in the +1 and +2 subsites;
      inhibition by cellobiose is certainly relieved in the mutant. The weaker binding
      of cellobiose is due to the loss of two water-mediated hydrogen bonds.

PMID- 11336633
TI  - The potential mechanism of the diabetogenic action of streptozotocin: inhibition
      of pancreatic beta-cell O-GlcNAc-selective N-acetyl-beta-D-glucosaminidase.
AB  - Streptozotocin (STZ), an analogue of GlcNAc, inhibits purified rat spleen O
      GlcNAc-selective N-acetyl-beta-D-glucosaminidase (O-GlcNAcase), the enzyme that
      removes O-GlcNAc from protein. We have shown previously that STZ increases
      pancreatic islet O-linked protein glycosylation. In light of these data, we
      investigated the possibility further that STZ causes beta-cell death by
      inhibiting O-GlcNAcase. In isolated islets, the time course and dose curve of STZ
      induced O-glycosylation correlated with beta-cell toxicity. STZ inhibition of rat
      islet O-GlcNAcase activity also paralleled that of its beta-cell toxicity, with
      significant inhibition occurring at a concentration of 1 mM. In contrast, STZ
      inhibition of rat brain O-GlcNAcase and beta-TC3 insulinoma cell O-GlcNAcase was
      significantly right-shifted compared with islets, with STZ only significantly
      inhibiting activity at a concentration of 5 mM, the same concentration required
      for beta-TC3 cell toxicity. In comparison, N-methyl-N-nitrosourea, the nitric
      oxide-donating portion of STZ, did not cause increased islet O-glycosylation,
      beta-cell toxicity or inhibition of beta-cell O-GlcNAcase. Enhanced STZ
      sensitivity of islet O-GlcNAcase compared with O-GlcNAcase from other tissues or
      an insulinoma cell line suggests why actual islet beta-cells are particularly
      sensitive to STZ. Confirming this idea, STZ-induced islet beta-cell toxicity was
      completely blocked by GlcNAc, which also prevented STZ-induced O-GlcNAcase
      inhibition, but was not even partially blocked by glucose, glucosamine or GalNAc.
      Together, these data demonstrate that STZ's inhibition of beta-cell O-GlcNAcase
      is the mechanism that accounts for its diabetogenic toxicity.

PMID- 11336634
TI  - Pterin interactions with distinct reductase activities of NO synthase.
AB  - Besides oxidizing L-arginine, neuronal NO synthase (NOS) NADPH-dependently
      reduces various electron acceptors, including cytochrome c and tetrazolium salts.
      The latter NADPH diaphorase reaction is used as a NOS-specific histochemical
      stain. Both reductase activities have been utilized to analyse electron transfer
      mechanisms within NOS. Basal L-arginine turnover by homodimeric NOS is enhanced
      by exogenous tetrahydrobiopterin, and the intra-subunit electron flow may include
      intermediate trihydrobiopterin. In the present work we have investigated the
      possible role of the tetrahydrobiopterin binding site of NOS in its reductase
      activities by examining the effects of anti-pterin type (PHS) NOS inhibitors.
      Although the type I anti-pterin, PHS-32, which does not affect basal dimeric NOS
      activity, also had no effect on either reductase activity, the type II anti
      pterin, PHS-72, which inhibits basal NOS activity, inhibited both reductase
      activities and the NADPH diaphorase histochemical stain. Pterin-free NOS monomers
      catalysed both cytochrome c and tetrazolium salt reduction. Our data suggest that
      both NOS reductase activities are independent of tetrahydrobiopterin. However,
      occupation of an exosite near the pterin site in NOS by type II anti-pterins may
      interfere with the electron flow within the active centre, suggesting that steric
      perturbation of the pterin binding pocket or reductase interaction contribute to
      the mechanism of inhibition by this class of NOS inhibitors.

PMID- 11336635
TI  - Cloning of a lymphatic peptide/histidine transporter.
AB  - Although peptide transport across the plasma membrane has been characterized well
      in the kidney and the intestine, the functional relevance of this transport in
      other organs has not been addressed. Here we report the cloning of a cDNA for a
      novel peptide/histidine transporter found in the rat (rPHT2), whose mRNA is
      expressed mainly in the lymphatic system. rPHT2 encodes a protein of 582 amino
      acids and showed 49% identity with the brain PHT (PHT1) [Yamashita, Shimada, Guo,
      Sato, Kohmura, Hayakawa, Takagi and Tohyama (1997) J. Biol. Chem. 272, 10205
      10211]. rPHT2 mRNA was abundant in lung, spleen and thymus, and detected faintly
      in brain, liver, adrenal gland and heart by Northern-blot analysis and reverse
      transcriptase PCR (RT-PCR). Intense signals for the gene were found in
      immunocytes using in situ hybridization. Ectopic expression of rPHT2 protein in
      HEK-293T cells and BHK cells was not found on the cell surface, but was found on
      the lysosomal membrane using light- and electron-microscopic analysis.
      Recombinant rPHT2 protein reconstituted into liposomes showed proton-dependent
      transport activity with histidine and histidyl-leucine. These findings suggest
      that rPHT2 is involved in the protein catabolic pathway in the lymphatic system.

PMID- 11336636
TI  - Subcellular distribution of chelatable iron: a laser scanning microscopic study
      in isolated hepatocytes and liver endothelial cells.
AB  - The pool of cellular chelatable iron ('free iron', 'low-molecular-weight iron',
      the 'labile iron pool') is usually considered to reside mainly within the
      cytosol. For the present study we adapted our previously established Phen Green
      method, based on quantitative laser scanning microscopy, to examine the
      subcellular distribution of chelatable iron in single intact cells for the first
      time. These measurements, performed in isolated rat hepatocytes and rat liver
      endothelial cells, showed considerable concentrations of chelatable iron, not
      only in the cytosol but also in several other subcellular compartments. In
      isolated rat hepatocytes we determined a chelatable iron concentration of 5.8+/
      2.6 microM within the cytosol and of at least 4.8 microM in mitochondria. The
      hepatocellular nucleus contained chelatable iron at the surprisingly high
      concentration of 6.6+/-2.9 microM. In rat liver endothelial cells, the
      concentration of chelatable iron within all these compartments was even higher
      (cytosol, 7.3+/-2.6 microM; nucleus, 11.8+/-3.9 microM; mitochondria, 9.2+/-2.7
      microM); in addition, chelatable iron (approx. 16+/-4 microM) was detected in a
      small subpopulation of the endosomal/lysosomal apparatus. Hence there is an
      uneven distribution of subcellular chelatable iron, a fact that is important to
      consider for (patho)physiological processes and that also has implications for
      the use of iron chelators to inhibit oxidative stress.

PMID- 11336637
TI  - Role of glycine-534 and glycine-1179 of human multidrug resistance protein (MDR1)
      in drug-mediated control of ATP hydrolysis.
AB  - The human multidrug resistance protein (MDR1) (P-glycoprotein), a member of the
      ATP-binding cassette (ABC) family, causes multidrug resistance by an active
      transport mechanism, which keeps the intracellular level of hydrophobic compounds
      below a cell-killing threshold. Human MDR1 variants with mutations affecting a
      conserved glycine residue within the ABC signature of either or both ABC units
      (G534D, G534V, G1179D and G534D/G1179D) were expressed and characterized in
      Spodoptera frugiperda (Sf9) cell membranes. These mutations caused a loss of
      measurable ATPase activity but still allowed ATP binding and the formation of a
      transition-state intermediate (nucleotide trapping). In contrast with the wild
      type protein, in which substrate drugs accelerate nucleotide trapping, in the ABC
      signature mutants nucleotide trapping was inhibited by MDR1-substrate drugs,
      suggesting a miscommunication between the drug-binding site(s) and the catalytic
      domains. Equivalent mutations of the two catalytic sites resulted in a similar
      effect, indicating the functional equivalence of the two sites. On the basis of
      these results and recent structural information on an ABC-ABC dimer [Hopfner,
      Karcher, Shin, Craig, Arthur, Carney and Tainer (2000) Cell 101, 789-800], we
      propose a key role of these glycine residues in the interdomain communication
      regulating drug-induced ATP hydrolysis.

PMID- 11336638
TI  - Induction of gene expression via activator protein-1 in the ascorbate protection
      against UV-induced damage.
AB  - UV irradiation is a major insult to the skin. We have shown previously that
      exogenous vitamin C (ascorbate) accumulates in HaCaT keratinocytes, thus
      conferring the ability to prevent radical formation and cell death elicited by UV
      B. Here, we have investigated the potential mechanisms accounting for the
      cytoprotective effects exerted by this antioxidant. Using a cDNA microarray
      hybridization, we identified several genes whose expression was up-regulated by
      ascorbate. We focused on the fra-1 gene, a member of the Fos family of
      transcription factors that down-regulates activator protein-1 (AP-1) target
      genes. Both in HaCaT and in normal human epidermal keratinocytes, we found Fra-1
      mRNA induction as early as 2 h after ascorbate loading. Electrophoretic mobility
      shift assay and antibody supershift analysis revealed that ascorbate modulates AP
      1 DNA-binding activity and that Fra-1 is in AP-1 complexes in treated cells.
      Furthermore, transient-transfection studies, using an AP-1 reporter construct,
      showed that ascorbate was able to inhibit both basal and UV-B-induced AP-1
      dependent transcription. Ascorbate also modulates UV-B-induced AP-1 activity by
      preventing the phosphorylation and activation of the upstream c-Jun N-terminal
      kinase (JNK), thus inhibiting phosphorylation of the endogenous c-Jun protein.
      These data suggest that ascorbate mediates cellular responses aimed at
      counteracting UV-mediated cell damage and cell death by interfering at multiple
      levels with the activity of the JNK/AP-1 pathway and modulating the expression of
      AP-1-regulated genes.

PMID- 11336639
TI  - Heterodimerization of the epidermal-growth-factor (EGF) receptor and ErbB2 and
      the affinity of EGF binding are regulated by different mechanisms.
AB  - When clathrin-dependent endocytosis is inhibited in HeLa cells by overexpression
      of a K44A (Lys(44)-->Ala) mutant of the GTPase dynamin, high-affinity binding of
      epidermal growth factor (EGF) to the EGF receptor (EGFR) is disrupted [Ringerike,
      Stang, Johannessen, Sandnes, Levy and Madshus (1998) J. Biol. Chem. 273, 16639
      16642]. We now report that the effect of [K44A]dynamin on EGF binding was
      counteracted by incubation with the non-specific kinase inhibitor staurosporine
      (SSP), implying that a protein kinase is responsible for disrupted high-affinity
      binding of EGF upon overexpression of [K44A]dynamin. The effect of [K44A]dynamin
      on EGF binding was not due to altered phosphorylation of the EGFR, suggesting
      that the activated kinase is responsible for phosphorylation of a substrate other
      than EGFR. The number of EGFR molecules was increased in cells overexpressing
      [K44A]dynamin, while the number of proto-oncoprotein ErbB2 molecules was
      unaltered. EGF-induced receptor dimerization was not influenced by overexpression
      of [K44A]dynamin. ErbB2-EGFR heterodimer formation was found to be ligand
      independent, and the number of heterodimers was not altered by overexpression of
      [K44A]dynamin. Neither SSP nor the phorbol ester PMA, which disrupts high
      affinity EGF-EGFR interaction, had any effect on the EGFR homo- or hetero
      dimerization. Furthermore, the EGF-induced tyrosine phosphorylation of ErbB2 was
      not affected by overexpression of [K44A]dynamin, implying that EGFR-ErbB2 dimers
      were fully functional. Our results strongly suggest that high-affinity binding of
      EGF and EGFR-ErbB2 heterodimerization are regulated by different mechanisms.

PMID- 11336640
TI  - HC fragment (C-terminal portion of the heavy chain) of tetanus toxin activates
      protein kinase C isoforms and phosphoproteins involved in signal transduction.
AB  - A recent report [Gil, Chaib-Oukadour, Pelliccioni and Aguilera (2000) FEBS Lett.
      481, 177-182] describes activation of signal transduction pathways by tetanus
      toxin (TeTx), a Zn(2+)-dependent endopeptidase synthesized by the Clostridium
      tetani bacillus, which is responsible for tetanus disease. In the present work,
      specific activation of protein kinase C (PKC) isoforms and of intracellular
      signal-transduction pathways, which include nerve-growth-factor (NGF) receptor
      trkA, phospholipase C(PLC)gamma-1 and extracellular regulated kinases (ERKs) 1
      and 2, by the recombinant C-terminal portion of the TeTx heavy chain (H(C)-TeTx)
      is reported. The activation of PKC isoforms was assessed through their
      translocation from the soluble (cytosolic) compartment to the membranous
      compartment, showing that clear translocation of PKC-alpha, -beta, -gamma and 
      delta isoforms exists, whereas PKC-epsilon showed a slight decrease in its
      soluble fraction immunoreactivity. The PKC-zeta isoform showed no consistent
      response. Using immunoprecipitation assays against phosphotyrosine residues, time
      and dose-dependent increases in tyrosine phosphorylation were observed in the
      trkA receptor, PLCgamma-1 and ERK-1/2. The effects shown by the H(C)-TeTx
      fragment on tyrosine phosphorylation were compared with the effects produced by
      NGF. The trkA and ERK-1/2 activation were corroborated using phospho-specific
      antibodies against trkA phosphorylated on Tyr(490), and antibodies against
      Thr/Tyr phosphorylated ERK-1/2. Moreover, PLCgamma-1 phosphorylation was
      supported by its H(C)-TeTx-induced translocation to the membranous compartment,
      an event related to PLCgamma-1 activation. Since H(C)-TeTx is the domain
      responsible for membrane binding and lacks catalytic activity, the activations
      described here must be exclusively triggered by the interaction of TeTx with a
      membrane component.

PMID- 11336641
TI  - Inhibition of neuronal nitric oxide synthase by 6-nitrocatecholamines, putative
      reaction products of nitric oxide with catecholamines under oxidative stress
      conditions.
AB  - 6-Nitrodopamine and 6-nitronoradrenaline (6-nitronorepinephrine), putative
      products of the nitric oxide (NO)-dependent nitration of dopamine and
      noradrenaline, are reported to be reversible, competitive inhibitors of neuronal
      nitric oxide synthase (nNOS) with K(i) values of 45 and 52 microM respectively.
      The nitrocatecholamines inhibited H(2)O(2) production in the absence of L
      arginine and tetrahydrobiopterin (BH(4)) (the IC(50) values for 6-nitrodopamine
      and 6-nitronoradrenaline were 85 and 55 microM respectively) but without
      affecting cytochrome c reduction. The apparent K(i) values for nitrocatecholamine
      inhibition of enzyme activation by BH(4) were 18 microM for 6-nitrodopamine and
      40 microM for 6-nitronoradrenaline. Both nitrocatecholamines antagonized the
      dimerization of nNOS induced by BH(4) and by L-arginine, the effect being
      reversed by BH(4) (more than 10 microM) and L-arginine (e.g. 100 microM).
      Overall, these results suggest that nitrocatecholamines interfere with nNOS
      activity by binding to the enzyme in the proximity of the substrate and BH(4)
      binding sites near the haem group.

PMID- 11336642
TI  - Simple, sensitive and accurate method for the quantification of prothrombin mRNA
      by using competitive PCR.
AB  - A method for the quantification of prothrombin (PT) mRNA species in hepatic
      tissues of rats was developed with the use of competitive PCR. To validate the
      quantification approach, sequential dilutions of total RNA from one of the
      samples were reverse transcribed. Their equivalent volumes were amplified
      together with a known amount of non-homologous competitor cDNA with identical
      nucleotide primers. The disparate sizes of target and competitor permitted the
      easy identification and quantification of bands in samples after densitometric
      analysis of ethidium bromide-stained agarose gels. Ratios of intensities of
      target and competitor bands were plotted against the initial amounts of total RNA
      species used, giving a linear relationship. The slope of this line was virtually
      identical with that obtained when the sample RNA was replaced with recombinant
      target cDNA, indicating that recombinant cDNA behaved in PCR identically with
      that made by reverse transcription and permitting the estimation of transcripts
      in reverse transcription reactions by using the recombinant counterpart of each
      as a standard. To avoid variation in the final results, the amount of competitor
      used in the assay was calculated separately from the equivalence point of the
      reverse-transcribed total RNA of one of the tissue samples; PCR was performed
      only for the minimum number of cycles required to detect products. A standard
      curve was made in each PCR run by amplifying differing amounts of recombinant
      cDNA species of PT or beta-actin together with a constant amount of its
      competitor. The numbers of transcripts in the tissues were then determined
      directly by PCR incorporating the same amount of respective competitor (as used
      in the standard curve) and comparing the ratios of products with the standard
      curve. Application of this method revealed that the median ratio of PT message to
      beta-actin message in hepatic tissues of 10 normal rats was 0.37, with a mean+/
      S.D. of 0.37+/-0.07 (range 0.27-0.47). Although the method was developed for the
      quantification of PT transcripts in liver, it can easily be used for non-hepatic
      tissues as well. The technique is simple, quick and sensitive and requires only a
      very small amount of substrate.

PMID- 11336643
TI  - Human alpha1-acid glycoprotein binds to CCR5 expressed on the plasma membrane of
      human primary macrophages.
AB  - We have reported previously that human alpha(1)-acid glycoprotein (AGP) inhibits
      the infection of human monocyte-derived macrophages (MDM) by R5 HIV-1, and that a
      disulphide-bridged peptide mimicking the clade B HIV-1 gp120 consensus V3 domain
      (V3Cs) binds specifically to CCR5 (the major co-receptor of R5 HIV strains) on
      these cells [Seddiki, Rabehi, Benjouad, Saffar, Ferriere, Gluckman and Gattegno
      (1997) Glycobiology 7, 1229-1236]. The present study demonstrates that AGP binds
      specifically to MDM at high- and low-affinity binding sites with K(d) values of
      16 nM and 4.9 microM respectively. The fact that heat denaturation of AGP only
      partly inhibited this binding (43%) suggests that protein-protein interactions
      are involved, as well as AGP glycans which are resistant to heat denaturation.
      Mannan, but not dextran, is a significant inhibitor (52%) of this binding, and
      sequential exoglycosidase treatment of AGP, which exposes penultimate mannose
      residues, has a strong stimulatory effect ( approximately 2.8-fold). Therefore
      AGP glycans (probably mannose residues) are involved, at least partly, in the
      binding of AGP to MDM. In addition, AGP inhibits the binding of V3Cs and
      macrophage inflammatory protein-1beta (MIP-1beta) to MDM. The anti-CCR5
      monoclonal antibody 2D7, specific for the second extracellular loop of CCR5, also
      inhibited AGP binding (67%), whereas anti-CCR5 antibodies specific for the C
      terminus of CCR5 region had no effect. Native AGP, like V3Cs (but not heat
      denatured AGP), binds to 46 and 33-36 kDa electroblotted AGP-bound MDM membrane
      ligands, characterized as CCR5 by their interactions with anti-CCR5 antibodies
      and with MIP-1beta. Therefore both AGP glycans and MDM CCR5 are involved in the
      binding of AGP to MDM. This suggests that the inhibitory effect of AGP on the
      infection of human primary macrophages by R5 HIV-1 may be related to specific
      binding of AGP to a macrophage membrane lectin or lectin-like component and to
      CCR5.

PMID- 11336644
TI  - Human tear lipocalin acts as an oxidative-stress-induced scavenger of potentially
      harmful lipid peroxidation products in a cell culture system.
AB  - Human tear lipocalin [lipocalin 1 (lcn-1); von Ebner's gland protein] is a member
      of the lipocalin superfamily that is known to bind an unusual variety of
      lipophilic ligands. Because of its properties and its tissue-specific expression
      it has been suggested that lcn-1 might act as a physiological protection factor
      of epithelia. Overexpression of lcn-1 under certain disease conditions supported
      such a function. However, experimental investigations into its exact biological
      role and its mode of expression were impeded because lcn-1 was previously found
      to be produced only in serous glands. To overcome this problem we therefore
      sought a cell line that produced lcn-1 endogenously. Using reverse-transcriptase
      mediated PCR analysis we found expression of lcn-1 in the human teratocarcinoma
      derived NT2 precursor cells. Under normal conditions the production of lcn-1 is
      low. However, treatment of the cells with H(2)O(2) or FeSO(4), which typically
      induce lipid peroxidation, significantly enhanced the expression of lcn-1.
      Binding studies revealed that arachidonic acid and several lipid peroxidation
      products including 7beta-hydroxycholesterol, 8-isoprostane and 13-hydroxy-9,11
      octadecadienoic acid specifically bind to lcn-1. To investigate the physiological
      consequence of this observation we purified holo-(lcn-1) from culture medium and
      extracted the bound ligands. The presence of F(2)-isoprostanes in the extracts
      obtained from the fractions containing lcn-1 indicates that these typical lipid
      peroxidation products are indeed ligands of the protein in vivo. These results
      support the idea that lcn-1 acts as a physiological scavenger of potentially
      harmful lipophilic molecules; lcn-1 might therefore be a novel member of the
      cellular defence against the deleterious effects of oxidative stress.

PMID- 11336645
TI  - Single-cell imaging of graded Ins(1,4,5)P3 production following G-protein-coupled
      receptor activation.
AB  - The pleckstrin homology domain of phospholipase Cdelta1 (PH(PLCdelta)) binds
      Ins(1,4,5)P(3) and PtdIns(4,5)P(2) specifically, and can be used to detect
      changes in Ins(1,4,5)P(3) in single cells. A fusion construct of PH(PLCdelta) and
      enhanced green fluorescent protein (EGFP-PH(PLCdelta)) associates with the plasma
      membrane due to its association with PtdIns(4,5)P(2). However, PH(PLCdelta) has
      greater affinity for Ins(1,4,5)P(3) than PtdIns(4,5)P(2), and translocates to the
      cytosol as Ins(1,4,5)P(3) levels rise. Prolonged activation of group I
      metabotropic glutamate receptor 1alpha expressed in Chinese-hamster ovary cells
      or endogenous M(3) muscarinic receptors in SH-SY5Y neuroblastoma cells gave an
      initial transient peak in translocation, followed by a sustained plateau phase.
      This closely followed changes in cell population Ins(1,4,5)P(3) mass, but not
      PtdIns(4,5)P(2) levels, which decreased monophasically, as determined by
      radioreceptor assay. Translocation thus provides a real-time method to follow
      increases in Ins(1,4,5)P(3). Graded changes in Ins(1,4,5)P(3) in Chinese-hamster
      ovary-lac-mGlu1alpha cells could be detected with increasing glutamate
      concentrations, and dual loading with fura 2 and EGFP-PH(PLCdelta) showed that
      changes in intracellular Ca(2+) concentration closely paralleled Ins(1,4,5)P(3)
      production. Moreover, Ins(1,4,5)P(3) accumulation and intracellular Ca(2+)
      mobilization within single cells is graded in nature and dependent on both
      agonist concentration and receptor density.

PMID- 11336646
TI  - Expression of a prenylation-deficient Rab4 inhibits the GLUT4 translocation
      induced by active phosphatidylinositol 3-kinase and protein kinase B.
AB  - The small GTPase Rab4 has been shown to participate in the subcellular
      distribution of GLUT4 under both basal and insulin-stimulated conditions in
      adipocytes. In the present work, we have characterized the effect of Rab4
      DeltaCT, a prenylation-deficient and thus cytosolic form of Rab4, in this
      process. We show that the expression of Rab4 DeltaCT in freshly isolated
      adipocytes inhibits insulin-induced GLUT4 translocation, but only when this
      protein is in its GTP-bound active form. Further, it not only blocks the effect
      of insulin, but also that of a hyperosmotic shock, but does not interfere with
      the effect of zinc ions on GLUT4 translocation. Rab4 DeltaCT was then shown to
      prevent GLUT4 translocation induced by the expression of an active form of
      phosphatidylinositol 3-kinase or of protein kinase B, without altering the
      activities of the enzymes. Our results are consistent with a role of Rab4 DeltaCT
      acting as a dominant negative protein towards Rab4, possibly by binding to Rab4
      effectors.

PMID- 11336647
TI  - Molten-globule structure and membrane binding of the N-terminal protease
      resistant domain (63-193) of the steroidogenic acute regulatory protein (StAR).
AB  - The first step in steroidogenesis is the movement of cholesterol from the outer
      to inner mitochondrial membrane; this movement is facilitated by the
      steroidogenic acute regulatory protein (StAR). StAR has molten-globule properties
      at low pH and a protease-resistant N-terminal domain at pH 4 and pH 8 comprising
      residues 63-193. To explore the mechanism of action of StAR we investigated the
      structural properties of the bacterially expressed N-terminal domain (63-193
      StAR) using CD, limited proteolysis and NMR. Far- and near-UV CD showed that the
      amount of secondary structure was greater at acidic than at neutral pH, but there
      was little tertiary structure at any pH. Unlike 63-193 StAR liberated from N-62
      StAR by proteolysis, biosynthetic 63-193 StAR was no longer resistant to trypsin
      or proteinase K at pH 7, or to pepsin at pH 4. Addition of trifluoroethanol and
      SDS increased secondary structure at pH 7, and dodecylphosphocholine and CHAPS
      increased secondary structure at pH 2, pH 4 and pH 7. However, none of these
      conditions induced tertiary structure, as monitored by near-UV CD or NMR.
      Liposomes of phosphatidylcholine, phosphatidylserine and their mixture increased
      secondary structure of 63-193 StAR at pH 7, as monitored by far-UV CD, and stable
      protein-liposome complexes were identified by gel-permeation chromatography.
      These results provide further evidence that the N-terminal domain of StAR is a
      molten globule, and provide evidence that this conformation facilitates the
      interaction of the N-terminal domain of StAR with membranes. We suggest that this
      interaction is the key to understanding the mechanism of StAR's action.

PMID- 11336648
TI  - Crustacean hyperglycaemic hormone (CHH)-like peptides and CHH-precursor-related
      peptides from pericardial organ neurosecretory cells in the shore crab, Carcinus
      maenas, are putatively spliced and modified products of multiple genes.
AB  - About 24 intrinsic neurosecretory neurons within the pericardial organs (POs) of
      the crab Carcinus maenas produce a novel crustacean hyperglycaemic hormone (CHH)
      like peptide (PO-CHH) and two CHH-precursor-related peptides (PO-CPRP I and II)
      as identified immunochemically and by peptide chemistry. Edman sequencing and MS
      revealed PO-CHH as a 73 amino acid peptide (8630 Da) with a free C-terminus. PO
      CHH and sinus gland CHH (SG-CHH) share an identical N-terminal sequence,
      positions 1-40, but the remaining sequence, positions 41-73 or 41-72, differs
      considerably. PO-CHH may have different precursors, as cDNA cloning of PO-derived
      mRNAs has revealed several similar forms, one exactly encoding the peptide. All
      PO-CHH cDNAs contain a nucleotide stretch coding for the SG-CHH(41-76) sequence
      in the 3'-untranslated region (UTR). Cloning of crab testis genomic DNA revealed
      at least four CHH genes, the structure of which suggest that PO-CHH and SG-CHH
      arise by alternative splicing of precursors and possibly post-transcriptional
      modification of PO-CHH. The genes encode four exons, separated by three variable
      introns, encoding part of a signal peptide (exon I), the remaining signal peptide
      residues, a CPRP, the PO-CHH(1-40)/SG-CHH(1-40) sequences (exon II), the
      remaining PO-CHH residues (exon III) and the remaining SG-CHH residues and a 3'
      UTR (exon IV). Precursor and gene structures are more closely related to those
      encoding related insect ion-transport peptides than to penaeid shrimp CHH genes.
      PO-CHH neither exhibits hyperglycaemic activity in vivo, nor does it inhibit Y
      organ ecdysteroid synthesis in vitro. From the morphology of the neurons it seems
      likely that novel functions remain to be discovered.

PMID- 11336649
TI  - Transcriptional regulation of the KEL gene and Kell protein expression in
      erythroid and non-erythroid cells.
AB  - The Kell blood-group antigen was originally reported to be a protein expressed in
      erythroid tissue only. Transcriptional analysis of the KEL promoter activity in
      human erythroleukaemia K562 and epithelial HeLa cells by electrophoretic mobility
      shift and supershift assays, chloramphenicol acetyltransferase assays, co
      transfection studies and site-directed mutagenesis provided the following
      results: (i) the KEL promoter exhibits a strong transcriptional activity in K562
      cells and, unexpectedly, a basal non-erythroid activity in HeLa cells, (ii) up
      regulation of the 5' distal promoter activity occurs only in the erythroid
      context, and (iii) two motifs localized in the exon 1 region, which bind the
      Sp1/Sp3 and the human GATA-1/Ku70/80 factors, were required for down-regulation
      of the promoter activity, but inhibition of the promoter activity by the
      repressing factors in HeLa cells was incomplete. KEL expression in HeLa cells was
      performed further by primer-extension analysis, which revealed the presence of a
      low amount of Kell transcript correlating with basal expression of the Kell
      protein in these cells, as shown by immunopurification and Western-blot analysis.
      DNA sequencing of the transcript revealed a sequence identical to that obtained
      from erythroid tissue. In human tissues, KEL expression was investigated by dot
      blot analysis and revealed high levels of Kell mRNAs, particularly in brain
      tissues, testis and lymphoid tissues. Moreover, most tissues analysed exhibited
      low levels of Kell transcripts. The Kell protein was also detected by
      immunohistochemistry in the Sertoli cells of the testis and in lymphoid tissues
      like spleen and tonsil, specifically localized in the follicular dendritic cells.
      Altogether, the results indicated that KEL expression is not restricted to
      erythroid tissue.

PMID- 11336650
TI  - Barley arabinoxylan arabinofuranohydrolases: purification, characterization and
      determination of primary structures from cDNA clones.
AB  - A family 51 arabinoxylan arabinofuranohydrolase, designated AXAH-I, has been
      purified from extracts of 7-day-old barley (Hordeum vulgare L.) seedlings by
      fractional precipitation with (NH(4))(2)SO(4) and ion-exchange chromatography.
      The enzyme has an apparent molecular mass of 65 kDa and releases L-arabinose from
      cereal cell wall arabinoxylans with a pH optimum of 4.3, a catalytic rate
      constant (k(cat)) of 6.9 s(-1) and a catalytic efficiency factor (k(cat)/K(m)) of
      0.76 (ml x s(-1) x mg(-1)). Whereas the hydrolysis of alpha-L-arabinofuranosyl
      residues linked to C(O)3 of backbone (1-->4)-beta-xylosyl residues proceeds at
      the fastest rate, alpha-L-arabinofuranosyl residues on doubly substituted xylosyl
      residues are also hydrolysed, at lower rates. A near full-length cDNA encoding
      barley AXAH-I indicates that the mature enzyme consists of 626 amino acid
      residues and has a calculated pI of 4.8. A second cDNA, which is 81% identical
      with that encoding AXAH-I, encodes another barley AXAH, which has been designated
      AXAH-II. The barley AXAHs are likely to have key roles in wall metabolism in
      cereals and other members of the Poaceae. Thus the enzymes could participate in
      the modification of the fine structure of arabinoxylan during wall deposition,
      maturation or expansion, or in wall turnover and the hydrolysis of arabinoxylans
      in germinated grain.

PMID- 11336651
TI  - Activation of store-mediated calcium entry by secretion-like coupling between the
      inositol 1,4,5-trisphosphate receptor type II and human transient receptor
      potential (hTrp1) channels in human platelets.
AB  - Physical coupling between inositol 1,4,5-trisphosphate (IP(3)) receptors and
      transient receptor potential (Trp) channels has been demonstrated in both
      transfected and normal cells as a candidate mechanism for the activation of store
      mediated Ca(2+) entry (SMCE). We have investigated the properties of the coupling
      between the type II IP(3) receptor and naturally expressed human Trp1 (hTrp1) in
      human platelets. Treatment with xestospongin C, an inhibitor of IP(3) receptor
      function, abolished SMCE and coupling between the IP(3) receptor and hTrp1. The
      coupling was activated by depletion of the intracellular Ca(2+) stores, and was
      reversed by refilling of the stores. We have also examined the role of actin
      filaments in the activation and maintenance of the coupling. Stabilization of the
      cortical actin network with jasplakinolide prevented the coupling, indicating
      that, as with secretion, the actin filaments at the cell periphery act as a
      negative clamp which prevents constitutive coupling. In addition, the actin
      cytoskeleton plays a positive role, since disruption of the actin network
      inhibited the coupling when the Ca(2+) stores were depleted. These results
      provide strong evidence for the activation of SMCE by a secretion-like coupling
      mechanism involving a reversible association between IP(3) receptors and hTrp1 in
      normal human cells.

PMID- 11336652
TI  - Isolation of ubiquitin-E2 (ubiquitin-conjugating enzyme) complexes from
      erythroleukaemia cells using immunoaffinity techniques.
AB  - A variety of ubiquitin-associated (or conjugated) proteins, including substrates
      and enzymes for the ubiquitin system, are present in eukaryotic cells. In the
      present study we developed a simple method for their isolation, consisting of
      immunoaffinity chromatography using the monoclonal antibody FK2, which recognizes
      the conjugated ubiquitin molecule. Using this method followed by gel filtration,
      we isolated multi-ubiquitinated proteins with high molecular masses (>30 kDa) and
      also ubiquitinthioester-linked and mono-ubiquitinated forms of ubiquitin
      conjugating (E2) enzymes, UbcH7 and UBE2N, together with mono-, di- and tri
      ubiquitin molecules, from the cytoplasmic extract of heat-shock-treated K562
      erythroleukaemia cells. We also demonstrated that the FK2 antibody was capable of
      precipitating a ubiquitin-UbcH7 thioester, but not free UbcH7, which enabled the
      measurement of the respective cellular levels separately. The immunoprecipitable
      ubiquitin-UbcH7 thioester was found only when the cells were treated with heat
      shock. These results suggest the usefulness of the immunoaffinity techniques for
      identifying and analysing the cellular enzyme/protein-ubiquitin complexes.

PMID- 11336653
TI  - Self-association and precursor protein binding of Saccharomyces cerevisiae
      Tom40p, the core component of the protein translocation channel of the
      mitochondrial outer membrane.
AB  - The precursor protein translocase of the mitochondrial outer membrane (Tom) is a
      multi-subunit complex containing receptors and a general import channel, of which
      the core component is Tom40p. Nuclear-encoded mitochondrial precursor proteins
      are first recognized by surface receptors and then pass through the import
      channel. The Tom complex has been purified; however, the protein-protein
      interactions that drive its assembly and maintain its stability have been
      difficult to study. Here we show that Saccharomyces cerevisiae Tom40p expressed
      in bacteria and purified to homogeneity associates efficiently with itself. The
      self-association is very strong and can withstand up to 4 M urea or 1 M salt. The
      tight self-association does not require the N-terminal segment of Tom40p.
      Furthermore, purified Tom40p preferentially recognizes the targeting sequence of
      mitochondrial precursor proteins. Although the binding of the targeting sequence
      to Tom40p is inhibited by urea concentrations in excess of 1 M, it is moderately
      resistant to 1 M salt. Simultaneous self-assembly and precursor protein binding
      suggest that Tom40p contains at least two different domains mediating these
      processes. The experimental approach described here should be useful for
      analysing protein-protein interactions involving individual or groups of
      components of the mitochondrial import machinery.

PMID- 11336654
TI  - Substitution of murine ferrochelatase glutamate-287 with glutamine or alanine
      leads to porphyrin substrate-bound variants.
AB  - Ferrochelatase (EC 4.99.1.1) is the terminal enzyme of the haem biosynthetic
      pathway and catalyses iron chelation into the protoporphyrin IX ring. Glutamate
      287 (E287) of murine mature ferrochelatase is a conserved residue in all known
      sequences of ferrochelatase, is present at the active site of the enzyme, as
      inferred from the Bacillus subtilis ferrochelatase three-dimensional structure,
      and is critical for enzyme activity. Substitution of E287 with either glutamine
      (Q) or alanine (A) yielded variants with lower enzymic activity than that of the
      wild-type ferrochelatase and with different absorption spectra from the wild-type
      enzyme. In contrast to the wild-type enzyme, the absorption spectra of the
      variants indicate that these enzymes, as purified, contain protoporphyrin IX.
      Identification and quantification of the porphyrin bound to the E287-directed
      variants indicate that approx. 80% of the total porphyrin corresponds to
      protoporphyrin IX. Significantly, rapid stopped-flow experiments of the E287A and
      E287Q variants demonstrate that reaction with Zn(2+) results in the formation of
      bound Zn-protoporphyrin IX, indicating that the endogenously bound protoporphyrin
      IX can be used as a substrate. Taken together, these findings suggest that the
      structural strain imposed by ferrochelatase on the porphyrin substrate as a
      critical step in the enzyme catalytic mechanism is also accomplished by the E287A
      and E287Q variants, but without the release of the product. Thus E287 in murine
      ferrochelatase appears to be critical for the catalytic process by controlling
      the release of the product.

PMID- 11336655
TI  - Inhibition of Escherichia coli CTP synthase by glutamate gamma-semialdehyde and
      the role of the allosteric effector GTP in glutamine hydrolysis.
AB  - Cytidine 5'-triphosphate synthase catalyses the ATP-dependent formation of CTP
      from UTP with either ammonia or glutamine as the source of nitrogen. When
      glutamine is the substrate, GTP is required as an allosteric effector to promote
      catalysis. Escherichia coli CTP synthase, overexpressed as a hexahistidine-tagged
      form, was purified to high specific activity with the use of metal-ion-affinity
      chromatography. Unfused CTP synthase, generated by the enzymic removal of the
      hexahistidine tag, displayed an activity identical with that of the purified
      native enzyme and was used to study the effect of GTP on the inhibition of
      enzymic activity by glutamate gamma-semialdehyde. Glutamate gamma-semialdehyde is
      expected to inhibit CTP synthase by reacting reversibly with the active-site Cys
      379 to form an analogue of a tetrahedral intermediate in glutamine hydrolysis.
      Indeed, glutamate gamma-semialdehyde is a potent linear mixed-type inhibitor of
      CTP synthase with respect to glutamine (K(is) 0.16+/-0.03 mM; K(ii) 0.4+/-0.1 mM)
      and a competitive inhibitor with respect to ammonia (K(i) 0.39+/-0.06 mM) in the
      presence of GTP at pH 8.0. The mutant enzyme (C379A), which is fully active with
      ammonia but has no glutamine-dependent activity, is not inhibited by glutamate
      gamma-semialdehyde. Although glutamate gamma-semialdehyde exists in solution
      primarily in its cyclic form, Delta(1)-pyrroline-5-carboxylate, the variation of
      inhibition with pH, and the weak inhibition by cyclic analogues of Delta(1)
      pyrroline-5-carboxylate (L-proline, L-2-pyrrolidone and pyrrole-2-carboxylate)
      confirm that the rare open-chain aldehyde species causes the inhibition. When
      ammonia is employed as the substrate in the absence of GTP, the enzyme's affinity
      for glutamate gamma-semialdehyde is decreased approx. 10-fold, indicating that
      the allosteric effector, GTP, functions by stabilizing the protein conformation
      that binds the tetrahedral intermediate(s) formed during glutamine hydrolysis.

PMID- 11336656
TI  - alpha1 Integrin cytoplasmic domain is involved in focal adhesion formation via
      association with intracellular proteins.
AB  - Integrins are heterodimeric adhesion receptors consisting of alpha- and beta
      subunits capable of binding extracellular matrix molecules as well as other
      adhesion receptors on neighbouring cells. These interactions induce various
      signal transduction pathways in many cell types, leading to cytoskeletal
      reorganization, phosphorylation and induction of gene expression. Integrin
      ligation leads to cytoplasmic protein-protein interactions requiring both
      integrin cytoplasmic domains, and these domains are initiation points for focal
      adhesion formation and subsequent signal transduction cascades. In previous
      studies we have shown that the very short cytoplasmic alpha1 tail is required for
      post-ligand events, such as cell spreading as well as actin stress-fibre
      formation. In the present paper we report that cells lacking the cytoplasmic
      domain of the alpha1 integrin subunit are unable to form proper focal adhesions
      and that phosphorylation on tyrosine residues of focal adhesion components is
      reduced on alpha1beta1-specific substrates. The alpha1 cytoplasmic sequence is a
      specific recognition site for focal adhesion components like paxillin, talin,
      alpha-actinin and pp125FAK. It seems to account for alpha1-specific signalling,
      since when peptides that mimic the cytoplasmic domain of alpha1 are transferred
      into cells, they influence alpha1beta1-specific adhesion, presumably by competing
      for binding partners. For alpha1 integrin/protein binding, the conserved Lys-Ile
      Gly-Phe-Phe-Lys-Arg motif and, in particular, the two lysine residues, are
      important.

PMID- 11336657
TI  - Chimaeras reveal the role of the catalytic core in the activation of the plasma
      membrane Ca2+ pump.
AB  - Isoform 2b of the plasma membrane calcium pump differs from the ubiquitous
      isoform 4b in the following: (a) higher basal activity in the absence of
      calmodulin; (b) higher affinity for calmodulin; and (c) higher affinity for
      Ca(2+) in the presence of calmodulin [Elwess, Filoteo, Enyedi and Penniston
      (1997) J. Biol. Chem. 272, 17981-17986]. To investigate which parts of the
      molecule determine these kinetic differences, we made four chimaeric constructs
      in which portions of isoform 2b were grafted into isoform 4b: chimaera I contains
      only the C-terminal regulatory region of isoform 2b; chimaera II contains the N
      terminal moiety of isoform 2b, including both cytoplasmic loops; chimaera III
      contains the sequence of isoform 2b starting from the N-terminus to after the end
      of the first (small) cytoplasmic loop; and chimaera IV contains only the second
      (large) cytoplasmic loop. Surprisingly, chimaera I showed low basal activity in
      the absence of calmodulin and low affinity for calmodulin, unlike isoform 2b. In
      contrast, the chimaera containing both loops showed high basal activity, and
      Ca(2+) activation curves (both in the absence and in the presence of calmodulin)
      similar to those of isoform 2b. The rates of activation by calmodulin and of
      inactivation by calmodulin removal were measured, and the apparent K(d) for
      calmodulin was calculated from the ratio between these rate constants. The order
      of affinity was: 2b=II>4b=IV>III=I. From these results it is clear that the
      construct that most closely resembles isoform 2b is chimaera II. This shows that,
      in order to obtain an enzyme with properties similar to those of isoform 2b, both
      cytoplasmic loops are needed.

PMID- 11336658
TI  - Effects of the human papilloma virus HPV-16 E7 oncoprotein on glycolysis and
      glutaminolysis: role of pyruvate kinase type M2 and the glycolytic-enzyme
      complex.
AB  - Proliferating and tumour cells express the glycolytic isoenzyme, pyruvate kinase
      type M2 (M2-PK), which occurs in a highly active tetrameric form and in a dimeric
      form with low affinity for phosphoenolpyruvate. The switch between the two forms
      regulates glycolytic phosphometabolite pools and the interaction between
      glycolysis and glutaminolysis. In the present study, we show the effects of
      oncoprotein E7 of the human papilloma virus (HPV)-16 (E7)-transformation on two
      NIH 3T3 cell strains with different metabolic characteristics. E7-transformation
      of the high glycolytic NIH 3T3 cell strain led to a shift of M2-PK to the dimeric
      form and, in consequence, to a decrease in the cellular pyruvate kinase mass
      action ratio, the glycolytic flux rate and the (ATP+GTP)/(UTP+CTP) ratio, as well
      as to an increase in fructose 1,6-bisphosphate (FBP) levels, glutamine
      consumption and cell proliferation. The low glycolytic NIH 3T3 cell strain is
      characterized by high pyruvate and glutamine consumption rates and by an
      intrinsically large amount of the dimeric form of M2-PK, which is correlated with
      high FBP levels, a low (ATP+GTP)/(CTP+UTP) ratio and a high proliferation rate.
      E7-transformation of this cell strain led to an alteration in the glycolytic
      enzyme complex that correlates with an increase in pyruvate and glutamine
      consumption and a slight increase in the flow of glucose to lactate. The
      association of phosphoglyceromutase within the glycolytic-enzyme complex led to
      an increase of glucose and serine consumption and a disruption of the linkage
      between glucose consumption and glutaminolysis. In both NIH 3T3 cell lines,
      transformation increased glutaminolysis and the positive correlation between
      alanine and lactate production.

PMID- 11336659
TI  - Cloning and identification of MYPT3: a prenylatable myosin targetting subunit of
      protein phosphatase 1.
AB  - To identify novel protein phosphatase 1 (PP1)-interacting proteins, a yeast two
      hybrid 3T3-L1 adipocyte cDNA library was screened with the catalytic subunit of
      PP1 as bait. In the present work, the isolation, identification and initial
      biochemical characterization of a novel PP1-interacting protein, MYPT3, which is
      homologous with the myosin phosphatase targetting subunit (MYPT) family, is
      described. MYPT3 aligns >99% with a region of mouse genomic DNA clone RP23-156P23
      and localizes to chromosome 15, between markers at 44.1-46.5 cM, as demonstrated
      by radiation hybrid mapping. The gene consists of ten exons that encode for a 524
      amino acid sequence with a predicted molecular mass of 57529 Da. The N-terminal
      region of MYPT3 consists of a consensus PP1-binding site and multiple ankyrin
      repeats. MYPT3 is distinguished from related approximately 110-130 kDa MYPT
      subunits by its molecular mass of 58 kDa, and a unique C-terminal region that
      contains several potential signalling motifs and a CaaX prenylation site. We have
      shown that affinity-purified glutathione S-transferase (GST)-MYPT3 is prenylated
      by purified recombinant farnesyltransferase in vitro. Endogenous PP1 from 3T3-L1
      lysates specifically interacts with MYPT3. Additionally, purified PP1 activity
      was inhibited by GST-MYPT3 toward phosphorylase a, myosin light chain and myosin
      substrate in vitro. Overall, our findings identify a novel prenylatable subunit
      of PP1 that defines a new subfamily of MYPT.

PMID- 11336660
TI  - Human oestrogenic 17beta-hydroxysteroid dehydrogenase specificity: enzyme
      regulation through an NADPH-dependent substrate inhibition towards the highly
      specific oestrone reduction.
AB  - Human oestrogenic 17beta-hydroxysteroid dehydrogenase (17beta-HSD1) catalyses the
      final step in the biosynthesis of all active oestrogens. Here we report the
      steady-state kinetics for 17beta-HSD1 at 37 degrees C and pH 7.5, using a
      homogeneous enzyme preparation with oestrone, dehydroepiandrosterone (DHEA) or
      dihydrotestosterone (DHT) as substrate and NADP(H) as the cofactor. Kinetic
      studies made over a wide range of oestrone concentrations (10 nM-10 microM)
      revealed a typical substrate-inhibition phenomenon. Data analysis using the
      substrate-inhibition equation v=V.[s]/[K(m)+[s](1+[s]/K(i))] gave a K(m) of
      0.07+/-0.01 microM, a k(cat) (for the dimer) of 1.5+/-0.1 s(-1), a specificity of
      21 microM(-1) x s(-1) and a K(i) of 1.3 microM. When NADH was used instead of
      NADPH, substrate inhibition was no longer observed and the kinetic constants were
      significantly modified to 0.42+/-0.07 microM for the K(m), 0.8+/-0.04 s(-1) for
      the k(cat) and 1.9 microM(-1) x s(-1) for the specificity. The modification of an
      amino acid in the cofactor-binding site (Leu36Asp) eliminated the substrate
      inhibition observed in the presence of NADPH, confirming the NADPH-dependence of
      the phenomenon. The possible formation of an enzyme-NADP(+)-oestrone dead-end
      complex during the substrate-inhibition process is supported by the competitive
      inhibition of oestradiol oxidation by oestrone. Kinetic studies performed with
      either DHEA (K(m)=24+/-4 microM; k(cat)=0.47+/-0.06 s(-1); specificity=0.002
      microM(-1) x s(-1)) or DHT (K(m)=26+/-6 microM; k(cat)=0.2+/-0.02 s(-1);
      specificity=0.0008 microM(-1) x s(-1)) in the presence of NADP(H) resulted in low
      specificities and no substrate inhibition. Taken together, our results
      demonstrate that the high specificity of 17beta-HSD1 towards oestrone is coupled
      with an NADPH-dependent substrate inhibition, suggesting that both the
      specificity and the enzyme control are provided for the cognate substrate.

PMID- 11336661
TI  - Cation-dependent structural features of beta-casein-(1-25).
AB  - Complete sequence-specific, proton-resonance assignments have been determined for
      the calcium phosphate-stabilizing tryptic peptide beta-casein-(1-25) containing
      the phosphorylated sequence motif Ser(P)(17)-Ser(P)-Ser(P)-Glu-Glu(21). Spectra
      of the peptide have been recorded, in separate experiments, in the presence of
      excess ammonium ions, sodium ions and calcium ions, and of the dephosphorylated
      peptide in the presence of excess sodium ions. We observed significant changes to
      chemical shifts for backbone and side-chain resonances that were dependent upon
      the nature of the cation present. Medium-range nuclear Overhauser effect (nOe)
      enhancements, characteristic of small structured regions in the peptide, were
      observed and also found to be cation dependent. The secondary structure of the
      peptide was characterized by sequential and medium-range (i, i+2/3/4, which
      denotes an interaction between residue i and residue i+2, i+3 or i+4 in the
      peptide) nOe connectivities, and Halpha chemical shifts. Four structured regions
      were identified in the calcium-bound peptide: residues Arg(1) to Glu(4) were
      involved in a loop-type structure, and residues Val(8) to Glu(11), Ser(P)(17) to
      Glu(20) and Glu(21) to Thr(24) were implicated in beta-turn conformations.
      Comparison of the patterns of medium-range nOe connectivities in beta-casein-(1
      25) with those in alpha(S1)-casein-(59-79) suggest that the two peptides have
      distinctly different conformations in the presence of calcium ions, despite
      having a high degree of sequential and functional similarity.

PMID- 11336663
TI  - The CONSORT statement: revised recommendations for improving the quality of
      reports of parallel group randomized trials.
AB  - To comprehend the results of a randomized controlled trial (RCT), readers must
      understand its design, conduct, analysis and interpretation. That goal can only
      be achieved through complete transparency from authors. Despite several decades
      of educational efforts, the reporting of RCTs needs improvement. Investigators
      and editors developed the original CONSORT (Consolidated Standards of Reporting
      Trials) statement to help authors improve reporting by using a checklist and flow
      diagram. The revised CONSORT statement presented in this paper incorporates new
      evidence and addresses some criticisms of the original statement.The checklist
      items pertain to the content of the Title, Abstract, Introduction, Methods,
      Results and Discussion. The revised checklist includes 22-items selected because
      empirical evidence indicates that not reporting the information is associated
      with biasedestimates of treatment effect or the information is essential to judge
      the reliability or relevance of the findings. We intended the flow diagram to
      depict the passage of participants through an RCT. The revised flow diagram
      depicts information from four stages of a trial (enrollment, intervention
      allocation, follow-up, and analysis). The diagram explicitly includes the number
      of participants, for each intervention group, included in the primary data
      analysis. Inclusion of these numbers allows the reader to judge whether the
      authors have performed an intention-to-treat analysis.In sum, the CONSORT
      statement is intended to improve the reporting of an RCT, enabling readers to
      understand a trial's conduct and to assess the validity of its results.

PMID- 11336662
TI  - Phosphatidylinositol transfer proteins and protein kinase C make separate but non
      interacting contributions to the phosphorylation state necessary for secretory
      competence in rat mast cells.
AB  - Mast cells permeabilized by streptolysin O undergo exocytosis when stimulated
      with Ca(2+) and guanosine 5'-[gamma-thio]triphosphate but become progressively
      refractory to this stimulus if it is delayed. This run-down of responsiveness
      occurs over a period of 20-30 min, during which the cells leak soluble and
      tethered proteins. We show here that withdrawal of ATP during the process of run
      down is strongly inhibitory but that as little as 25 microM ATP can extend
      responsiveness significantly; this effect is maximal at 50 microM. When
      phosphatidylinositol transfer proteins (PITPs) are provided to cells at the time
      of permeabilization, run-down is retarded. We conclude that in the presence of
      ATP they convey substrates for phosphorylation that are essential for exocytosis
      and thus interact with the regulatory machinery. Furthermore, we show that
      PITPalpha and PITPbeta have additive effects in this mechanism, suggesting that
      they are not functionally redundant. Alternatively, secretion from run-down cells
      can be inhibited by the aminoglycoside antibiotic neomycin, which is understood
      to bind to phosphoinositide headgroups, and by a PH (pleckstrin homology) domain
      polypeptide that binds phosphoinositides. The apparent displacement of neomycin
      by exogenous PITPs suggests that these proteins screen essential lipids.
      Secretion from run-down cells is also inhibited by 1-O-hexadecyl-2-O-methyl-rac
      glycerol (AMG-C(16)), an inhibitor of protein kinase C. The lack of synergy
      between neomycin and AMG-C(16) suggests that protein kinase C independently
      provides a second essential component through protein phosphorylation and that
      there are two independent phosphorylation pathways necessary for secretion
      competence.

PMID- 11336664
TI  - Deciphering NAD-dependent deacetylases.

PMID- 11336665
TI  - A conserved regulatory system for aging.

PMID- 11336666
TI  - Mesendoderm. an ancient germ layer?

PMID- 11336667
TI  - Working in the post-genomic C. elegans world.

PMID- 11336668
TI  - Artemis, a novel DNA double-strand break repair/V(D)J recombination protein, is
      mutated in human severe combined immune deficiency.
AB  - The V(D)J recombination process insures the somatic diversification of
      immunoglobulin and antigen T cell receptor encoding genes. This reaction is
      initiated by a DNA double-strand break (dsb), which is resolved by the
      ubiquitously expressed DNA repair machinery. Human T-B-severe combined
      immunodeficiency associated with increased cellular radiosensitivity (RS-SCID) is
      characterized by a defect in the V(D)J recombination leading to an early arrest
      of both B and T cell maturation. We previously mapped the disease-related locus
      to the short arm of chromosome 10. We herein describe the cloning of the gene
      encoding a novel protein involved in V(D)J recombination/DNA repair, Artemis,
      whose mutations cause human RS-SCID. Protein sequence analysis strongly suggests
      that Artemis belongs to the metallo-beta-lactamase superfamily.

PMID- 11336669
TI  - The human peroxisomal targeting signal receptor, Pex5p, is translocated into the
      peroxisomal matrix and recycled to the cytosol.
AB  - Peroxisomal targeting signals (PTSs) are recognized by predominantly cytosolic
      receptors, Pex5p and Pex7p. The fate of these PTS receptors following their
      interactions on the peroxisomal membrane with components of docking and putative
      translocation complexes is unknown. Using both novel and multiple experimental
      approaches, we show that human Pex5p does not just bind cargo and deliver it to
      the peroxisome membrane, but participates in multiple rounds of entry into the
      peroxisome matrix and export to the cytosol independent of the PTS2 import
      pathway. This unusual shuttling mechanism for the PTS1 receptor distinguishes
      protein import into peroxisomes from that into most other organelles, with the
      exception of the nucleus.

PMID- 11336670
TI  - Apical localization of wingless transcripts is required for wingless signaling.
AB  - Many developing and adult tissues are comprised of polarized epithelia. Proteins
      that are asymmetrically distributed in these cells are thought to be localized by
      protein trafficking. Here we show that the distribution and function of the
      signaling protein Wingless is predetermined by the subcellular localization of
      its mRNA. High-resolution in situ hybridization reveals apical transcript
      localization in the majority of tissues examined. This localization is mediated
      by two independently acting elements in the 3' UTR. Replacement of these elements
      with non- or basolaterally localizing elements yields proteins with altered
      intracellular and extracellular distributions and reduced signaling activities.
      This novel aspect of the wingless signaling pathway is conserved and may prove to
      be a mechanism used commonly for establishing epithelial cell polarity.

PMID- 11336671
TI  - Drosophila wingless and pair-rule transcripts localize apically by dynein
      mediated transport of RNA particles.
AB  - Asymmetric mRNA localization targets proteins to their cytoplasmic site of
      function. We have elucidated the mechanism of apical localization of wingless and
      pair-rule transcripts in the Drosophila blastoderm embryo by directly visualizing
      intermediates along the entire path of transcript movement. After release from
      their site of transcription, mRNAs diffuse within the nucleus and are exported to
      all parts of the cytoplasm, regardless of their cytoplasmic destinations.
      Endogenous and injected apical RNAs assemble selectively into cytoplasmic
      particles that are transported apically along microtubules. Cytoplasmic dynein is
      required for correct localization of endogenous transcripts and apical movement
      of injected RNA particles. We propose that dynein-dependent movement of RNA
      particles is a widely deployed mechanism for mRNA localization.

PMID- 11336672
TI  - The CaMKII UNC-43 activates the MAPKKK NSY-1 to execute a lateral signaling
      decision required for asymmetric olfactory neuron fates.
AB  - A stochastic cell fate decision mediated by axon contact and calcium signaling
      causes one of the two bilaterally symmetric AWC neurons, either AWCL or AWCR, to
      express the candidate olfactory receptor str-2. nsy-1 mutants express str-2 in
      both neurons, disrupting AWC asymmetry. nsy-1 encodes a homolog of the human MAP
      kinase kinase kinase (MAPKKK) ASK1, an activator of JNK and p38 kinases. Based on
      genetic epistasis analysis, nsy-1 appears to act downstream of the CaMKII unc-43,
      and NSY-1 associates with UNC-43, suggesting that UNC-43/CaMKII activates the NSY
      1 MAP kinase cassette. Mosaic analysis demonstrates that UNC-43 and NSY-1 act
      primarily in a cell-autonomous execution step that represses str-2 expression in
      one AWC cell, downstream of the initial lateral signaling pathway that
      coordinates the fates of the two cells.

PMID- 11336673
TI  - EphA receptors regulate growth cone dynamics through the novel guanine nucleotide
      exchange factor ephexin.
AB  - Eph receptors transduce short-range repulsive signals for axon guidance by
      modulating actin dynamics within growth cones. We report the cloning and
      characterization of ephexin, a novel Eph receptor-interacting protein that is a
      member of the Dbl family of guanine nucleotide exchange factors (GEFs) for Rho
      GTPases. Ephrin-A stimulation of EphA receptors modulates the activity of ephexin
      leading to RhoA activation, Cdc42 and Rac1 inhibition, and cell morphology
      changes. In addition, expression of a mutant form of ephexin in primary neurons
      interferes with ephrin-A-induced growth cone collapse. The association of ephexin
      with Eph receptors constitutes a molecular link between Eph receptors and the
      actin cytoskeleton and provides a novel mechanism for achieving highly localized
      regulation of growth cone motility.

PMID- 11336674
TI  - Structural basis for guanine nucleotide exchange on Ran by the regulator of
      chromosome condensation (RCC1).
AB  - RCC1 (regulator of chromosome condensation), a beta propeller chromatin-bound
      protein, is the guanine nucleotide exchange factor (GEF) for the nuclear GTP
      binding protein Ran. We report here the 1.8 A crystal structure of a Ran*RCC1
      complex in the absence of nucleotide, an intermediate in the multistep GEF
      reaction. In contrast to previous structures, the phosphate binding region of the
      nucleotide binding site is perturbed only marginally, possibly due to the
      presence of a polyvalent anion in the P loop. Biochemical experiments show that a
      sulfate ion stabilizes the Ran*RCC1 complex and inhibits dissociation by guanine
      nucleotides. Based on the available structural and biochemical evidence, we
      present a unified scenario for the GEF mechanism where interaction of the P loop
      lysine with an acidic residue is a crucial element for the overall reaction.

PMID- 11336675
TI  - Crystal structure of the 14-3-3zeta:serotonin N-acetyltransferase complex. a role
      for scaffolding in enzyme regulation.
AB  - Serotonin N-acetyltransferase (AANAT) controls the daily rhythm in melatonin
      synthesis. When isolated from tissue, AANAT copurifies with isoforms epsilon and
      zeta of 14-3-3. We have determined the structure of AANAT bound to 14-3-3zeta, an
      association that is phosphorylation dependent. AANAT is bound in the central
      channel of the 14-3-3zeta dimer, and is held in place by extensive interactions
      both with the amphipathic phosphopeptide binding groove of 14-3-3zeta and with
      other parts of the central channel. Thermodynamic and activity measurements,
      together with crystallographic analysis, indicate that binding of AANAT by 14-3
      3zeta modulates AANAT's activity and affinity for its substrates by stabilizing a
      region of AANAT involved in substrate binding.

PMID- 11336676
TI  - Crystal structure of a SIR2 homolog-NAD complex.
AB  - The SIR2 protein family comprises a novel class of nicotinamide-adenine
      dinucleotide (NAD)-dependent protein deacetylases that function in
      transcriptional silencing, DNA repair, and life-span extension in Saccharomyces
      cerevisiae. Two crystal structures of a SIR2 homolog from Archaeoglobus fulgidus
      complexed with NAD have been determined at 2.1 A and 2.4 A resolutions. The
      structures reveal that the protein consists of a large domain having a Rossmann
      fold and a small domain containing a three-stranded zinc ribbon motif. NAD is
      bound in a pocket between the two domains. A distinct mode of NAD binding and an
      unusual configuration of the zinc ribbon motif are observed. The structures also
      provide important insights into the catalytic mechanism of NAD-dependent protein
      deacetylation by this family of enzymes.

PMID- 11336677
TI  - Structure of Pumilio reveals similarity between RNA and peptide binding motifs.
AB  - Translation regulation plays an essential role in the differentiation and
      development of animal cells. One well-studied case is the control of hunchback
      mRNA during early Drosophila embryogenesis by the trans-acting factors Pumilio,
      Nanos, and Brain Tumor. We report here a crystal structure of the critical region
      of Pumilio, the Puf domain, that organizes a multivalent repression complex on
      the 3' untranslated region of hunchback mRNA. The structure reveals an extended,
      rainbow shaped molecule, with tandem helical repeats that bear unexpected
      resemblance to the armadillo repeats in beta-catenin and the HEAT repeats in
      protein phosphatase 2A. Based on the structure and genetic experiments, we
      identify putative interaction surfaces for hunchback mRNA and the cofactors Nanos
      and Brain Tumor. This analysis suggests that similar features in helical repeat
      proteins are used to bind extended peptides and RNA.

PMID- 11336680
TI  - HLA DNA typing and transplantation.

PMID- 11336681
TI  - Dendritic cells in transplantation--friend or foe?

PMID- 11336682
TI  - Innate immune responses to transplants: a significant variable with cadaver
      donors.

PMID- 11336683
TI  - Chemokines, chemokine receptors, and allograft rejection.

PMID- 11336684
TI  - Chronic rejection.

PMID- 11336685
TI  - Regulating the immune response to transplants. a role for CD4+ regulatory cells?

PMID- 11336686
TI  - T cell death and transplantation tolerance.

PMID- 11336687
TI  - Mixed chimerism and transplant tolerance.

PMID- 11336688
TI  - Toward regenerative medicine.

PMID- 11336689
TI  - The immunological barrier to xenotransplantation.

PMID- 11336690
TI  - Regulation of IL-4 gene expression by distal regulatory elements and GATA-3 at
      the chromatin level.
AB  - Using a transgenic approach, we examined distal regulatory elements located in
      the IL-4 locus and the role of GATA-3 at these elements. The intergenic DNase I
      hypersensitive sites (HSS) showed strong enhancement, and the intronic enhancer
      (IE) and HS5/HS5a sites showed weaker enhancement of the IL-4 promoter. Elements
      in the 3' region of the IL-4 gene contributed to Th2 specificity. All individual
      enhancers were T cell activation dependent but not Th2 specific, with the
      exception of IE. However, when these distal elements were combined into a
      "minilocus," expression was strongly enhanced and Th2 specific. GATA-3 mediated
      strong enhancement of IL-4 promoter activity in Th1 cells when the promoter was
      embedded in the minilocus or linked to HSS and IE, demonstrating that GATA-3 acts
      through these elements to regulate IL-4 gene expression.

PMID- 11336691
TI  - Type i interferons potently enhance humoral immunity and can promote isotype
      switching by stimulating dendritic cells in vivo.
AB  - Type I interferons (IFN-I) are rapidly induced following infection and play a key
      role in nonspecific inhibition of virus replication. Here we have investigated
      the effects of IFN-I on the generation of antigen-specific antibody responses.
      The data show that IFN-I potently enhance the primary antibody response to a
      soluble protein, stimulating the production of all subclasses of IgG, and induce
      long-lived antibody production and immunological memory. In addition, endogenous
      production of IFN-I was shown to be essential for the adjuvant activity of CFA.
      Finally, IFN-I enhanced the antibody response and induced isotype switching when
      dendritic cells were the only cell type responding to IFN-I. The data reveal the
      potent adjuvant activity of IFN-I and their important role in linking innate and
      adaptive immunity.

PMID- 11336692
TI  - Age-dependent T cell tolerance and autoimmunity to myelin basic protein.
AB  - Experimental autoimmune encephalomyelitis (EAE), an animal model for multiple
      sclerosis, is induced by activating a subset of myelin basic protein (MBP)
      specific T cells that have escaped tolerance induction. Here, we define the
      tolerance mechanisms that eliminate the majority of MBP-specific T cells from the
      periphery. We show that MBP-specific T cells undergo central tolerance mediated
      by bone marrow-derived antigen-presenting cells presenting exogenously derived
      MBP epitopes. The efficiency of tolerance is age dependent, reflecting the
      developmentally regulated expression of MBP. Dependence of tolerance on the
      amount of MBP expressed in vivo results in an age window of susceptibility to EAE
      in mice that peaks during puberty. These results suggest that factors regulating
      expression of self-antigens in vivo can influence susceptibility to autoimmunity.

PMID- 11336693
TI  - Strength of signaling by CD4 and CD8 coreceptor tails determines the number but
      not the lineage direction of positively selected thymocytes.
AB  - The present study has assessed the impact of the intracellular domains of CD4 and
      CD8 on positive selection and lineage direction of MHC class I-restricted
      thymocytes. Contrary to current presumption, we found that the CD4 tail promotes
      the generation of both CD4+ and CD8+ T cells without preference for the CD4+ T
      cell lineage. We also found that the identity of the coreceptor tail and hence
      the strength of coreceptor signaling determine the number of thymocytes
      undergoing positive selection but not their ultimate CD4/CD8 phenotype. These
      findings demonstrate that the strength of coreceptor signaling has a significant
      quantitative but not qualitative impact on positive selection and provide a
      simple explanation for the greater numbers of CD4+ than CD8+ T cells selected in
      the normal thymus.

PMID- 11336694
TI  - Short telomeres in yeast are highly recombinogenic.
AB  - We report that recombination rates specifically increase by up to 10(3) near
      shortened telomeres in K. lactis cells. This occurs in cells lacking telomerase
      that undergo growth senescence as well as in cells with stably shortened
      telomeres that cause little effect on cell growth. The high rates of gene
      conversion allowed a subtelomeric marker, initially present at a single telomere,
      to efficiently spread to most or all other telomeres in the cell. We propose that
      short telomeres in K. lactis are not fully competent at capping chromosome ends
      and hence are occasionally processed by proteins that normally act to repair
      broken DNA ends through recombination. This helps explain how recombination can
      be frequent enough to permit maintenance of telomeres in yeast cells lacking
      telomerase.

PMID- 11336695
TI  - An origin-deficient yeast artificial chromosome triggers a cell cycle checkpoint.
AB  - Checkpoint controls coordinate entry into mitosis with the completion of DNA
      replication. Depletion of nucleotide precursors by treatment with the drug
      hydroxyurea triggers such a checkpoint response. However, it is not clear whether
      the signal for this hydroxyurea-induced checkpoint pathway is the presence of
      unreplicated DNA, or rather the persistence of single-stranded or damaged DNA. In
      a yeast artificial chromosome (YAC) we have engineered an approximately 170 kb
      region lacking efficient replication origins that allows us to explore the
      specific effects of unreplicated DNA on cell cycle progression. Replication of
      this YAC extends the length of S phase and causes cells to engage an S/M
      checkpoint. In the absence of Rad9 the YAC becomes unstable, undergoing deletions
      within the origin-free region.

PMID- 11336696
TI  - The large subunit of replication factor C promotes cell survival after DNA damage
      in an LxCxE motif- and Rb-dependent manner.
AB  - Retinoblastoma (Rb) protein promotes cell survival after DNA damage. We show here
      that the LxCxE binding site in Rb mediates both cell survival and cell-cycle
      arrest after DNA damage. Replication factor C (RF-C) complex plays an important
      role in DNA replication. We describe a novel function of the large subunit of RF
      C in promoting cell survival after DNA damage. RF-Cp145 contains an LxCxE motif,
      and mutation of this motif abolishes the protective effect of RF-Cp145. The
      inability of wild-type RF-Cp145 to promote cell survival in Rb-null cells is
      rescued by Rb but not by Rb mutants defective in binding LxCxE proteins. RF-C
      thus enhances cell survival after DNA damage in an Rb-dependent manner.

PMID- 11336697
TI  - Heterochromatin formation in mammalian cells: interaction between histones and
      HP1 proteins.
AB  - Members of the heterochromatin protein 1 (HP1) family are silencing nonhistone
      proteins. Here, we show that in P19 embryonal carcinoma (EC) nuclei, HP1 alpha,
      beta, and gamma form homo- and heteromers associated with nucleosomal core
      histones. In vitro, all three HP1s bind to tailed and tailless nucleosomes and
      specifically interact with the histone-fold of histone H3. Furthermore, HP1alpha
      interacts with the linker histone H1. HP1alpha binds to H3 and H1 through its
      chromodomain (CD) and hinge region, respectively. Interestingly, the Polycomb
      (Pc1/M33) CD also interacts with H3, and HP1alpha and Pc1/M33 binding to H3 is
      severely impaired by CD mutations known to abrogate HP1 and Polycomb silencing in
      Drosophila. These results define a novel function for the conserved CD and
      suggest that HP1 self-association and histone binding may play a crucial role in
      HP1-mediated heterochromatin assembly.

PMID- 11336698
TI  - A Rsc3/Rsc30 zinc cluster dimer reveals novel roles for the chromatin remodeler
      RSC in gene expression and cell cycle control.
AB  - Chromatin remodeling complexes perform central roles in transcriptional
      regulation. Here, we identify Rsc3 and Rsc30 as novel components of the essential
      yeast remodeler RSC complex. Rsc3 and Rsc30 function requires their zinc cluster
      domain, a known site-specific DNA binding motif. RSC3 is essential, and rsc3 Ts-
      mutants display a G2/M cell cycle arrest involving the spindle assembly
      checkpoint pathway, whereas rsc30Delta mutants are viable and osmosensitive. Rsc3
      and Rsc30 interact functionally and also physically as a stable Rsc3/Rsc30
      heteromeric complex. However, DNA microarray analysis with rsc3 or rsc30 mutants
      reveals different effects on the expression levels of ribosomal protein genes and
      cell wall genes. We propose that Rsc3 and Rsc30 interact physically but have
      different roles in targeting or regulating RSC.

PMID- 11336699
TI  - Bonus, a Drosophila homolog of TIF1 proteins, interacts with nuclear receptors
      and can inhibit betaFTZ-F1-dependent transcription.
AB  - The Drosophila bonus (bon) gene encodes a homolog of the vertebrate TIF1
      transcriptional cofactors. bon is required for male viability, molting, and
      numerous events in metamorphosis including leg elongation, bristle development,
      and pigmentation. Most of these processes are associated with genes that have
      been implicated in the ecdysone pathway, a nuclear hormone receptor pathway
      required throughout Drosophila development. Bon is associated with sites on the
      polytene chromosomes and can interact with numerous Drosophila nuclear receptor
      proteins. Bon binds via an LxxLL motif to the AF-2 activation domain present in
      the ligand binding domain of betaFTZ-F1 and behaves as a transcriptional
      inhibitor in vivo.

PMID- 11336700
TI  - Stress-induced map kinase Hog1 is part of transcription activation complexes.
AB  - In response to hyperosmotic environments, most eukaryotic cells activate a
      specialized mitogen-activated protein (MAP) kinase pathway. In S. cerevisiae, the
      key protein kinase, Hog1, coordinates the transcriptional induction of a variety
      of genes devoted to osmoadaptation and general stress protection. Depending on
      the promoter context, Hog1 can function through a variety of structurally
      unrelated transcription factors. Using chromatin precipitation assays, we
      discovered that the kinase itself becomes intimately linked with promoter regions
      during stress responses. This interaction is dependent on the presence of stress
      mediating transcriptional activators. In turn, Hog1 modulates promoter
      association of at least one of these factors. Additional findings highlight the
      possibility that Hog1 constitutes an integral part of the upstream activation
      complex, perhaps targeting not only the activator but also components of the
      general transcription machinery.

PMID- 11336701
TI  - Tyrosine phosphorylation-independent nuclear translocation of a dictyostelium
      STAT in response to DIF signaling.
AB  - We describe a Dictyostelium STAT, Dd-STATc, which regulates the speed of early
      development and the timing of terminal differentiation. Dd-STATc also functions
      as a repressor, which directs graded expression of the ecmA gene in different
      prestalk cell populations. Developing Dictyostelium cells produce a chlorinated
      hexaphenone, DIF, which directs prestalk cell differentiation. Dd-STATc is
      tyrosine phosphorylated, dimerizes, and translocates to the nucleus when cells
      are exposed to DIF. Surprisingly, however, SH2 domain-phosphotyrosine interaction
      is not necessary for the DIF-induced nuclear translocation of Dd-STATc. In this
      respect, Dd-STATc activation resembles several recently described, noncanonical
      mammalian STAT signaling processes. We show instead that DIF mediates nuclear
      translocation via sequences located in the divergent, N-terminal half of the Dd
      STATc molecule.

PMID- 11336702
TI  - BMP4 plays a key role in left-right patterning in chick embryos by maintaining
      Sonic Hedgehog asymmetry.
AB  - In chick embryos, the first signs of left-right asymmetry are detected in
      Hensen's node, essentially by left-sided Sonic Hedgehog (Shh) expression. After a
      gap of several hours, SHH induces polarized gene activities in the left paraxial
      mesoderm. We show that during this time period, BMP4 signaling is necessary and
      sufficient to maintain Shh asymmetry within the node. SHH and BMP4 proteins
      negatively regulate each other's transcription, resulting in a strict
      complementarity between these two gene patterns on each side of the node. Noggin,
      present in the midline at this stage, limits BMP4 spreading. Moreover, BMP4 is
      downstream to Activin signals and controls Fgf8. Thus, early BMP4 signaling
      coordinates left and right pathways in Hensen's node.

PMID- 11336703
TI  - Low-density lipoprotein receptor-related protein-5 binds to Axin and regulates
      the canonical Wnt signaling pathway.
AB  - To understand how the Wnt coreceptor LRP-5 is involved in transducing the
      canonical Wnt signals, we identified Axin as a protein that interacts with the
      intracellular domain of LRP-5. LRP-5, when expressed in fibroblast cells, showed
      no effect on the canonical Wnt signaling pathway by itself, but acted
      synergistically with Wnt. In contrast, LRP-5 mutants lacking the extracellular
      domain functioned as constitutively active forms that bind Axin and that induce
      LEF-1 activation by destabilizing Axin and stabilizing beta-catenin. Addition of
      Wnt caused the translocation of Axin to the membrane and enhanced the interaction
      between Axin and LRP-5. In addition, the LRP-5 sequences involved in interactions
      with Axin are required for LEF-1 activation. Thus, we conclude that the binding
      of Axin to LRP-5 is an important part of the Wnt signal transduction pathway.

PMID- 11336704
TI  - Cell surface glypicans are low-affinity endostatin receptors.
AB  - Endostatin, a collagen XVIII fragment, is a potent anti-angiogenic protein. We
      sought to identify its endothelial cell surface receptor(s). Alkaline phosphatase
      tagged endostatin bound endothelial cells revealing two binding affinities.
      Expression cloning identified glypican, a cell surface proteoglycan as the lower
      affinity receptor. Biochemical and genetic studies indicated that glypicans'
      heparan sulfate glycosaminoglycans were critical for endostatin binding.
      Furthermore, endostatin selected a specific octasulfated hexasaccharide from a
      sequence in heparin. We have also demonstrated a role for endostatin in renal
      tubular cell branching morphogenesis and show that glypicans serve as low
      affinity receptors for endostatin in these cells, as in endothelial cells.
      Finally, antisense experiments suggest the critical importance of glypicans in
      mediating endostatin activities.

PMID- 11336705
TI  - Tuberin-dependent membrane localization of polycystin-1: a functional link
      between polycystic kidney disease and the TSC2 tumor suppressor gene.
AB  - The PKD1 gene accounts for 85% of autosomal dominant polycystic kidney disease
      (ADPKD), the most common human genetic disorder. Rats with a germline
      inactivation of one allele of the Tsc2 tumor suppressor gene developed early
      onset severe bilateral polycystic kidney disease, with similarities to the human
      contiguous gene syndrome caused by germline codeletion of PKD1 and TSC2 genes.
      Polycystic rat renal cells retained two normal Pkd1 alleles but were null for
      Tsc2 and exhibited loss of lateral membrane-localized polycystin-1. In tuberin
      deficient cells, intracellular trafficking of polycystin-1 was disrupted,
      resulting in sequestration of polycystin-1 within the Golgi and reexpression of
      Tsc2 restored correct polycystin-1 membrane localization. These data identify
      tuberin as a determinant of polycystin-1 functional localization and,
      potentially, ADPKD severity.

PMID- 11336706
TI  - Signaling by human herpesvirus 8 kaposin A through direct membrane recruitment of
      cytohesin-1.
AB  - The induction of a transformed cellular phenotype by viruses requires the
      modulation of signaling pathways through viral proteins. We show here that the
      phenotypic changes induced by the kaposin A protein of human herpesvirus 8 are
      mediated through its direct interaction with cytohesin-1, a guanine nucleotide
      exchange factor for ARF GTPases and regulator of integrin-mediated cell adhesion.
      Focus formation, stress fiber dissolution, and activation of the ERK-1/2 MAP
      kinase signal cascade were reverted by the cytohesin-1 E157K mutant, which is
      deficient in catalyzing guanine nucleotide exchange. Furthermore, liposome
      embedded kaposin A specifically stimulates cytohesin-1 dependent GTP binding of
      myristoylated ARF1 in vitro. These results suggest a previously unknown
      involvement of ARF GTPases in the control of cellular functions by herpesviruses.

PMID- 11336707
TI  - Self-assembly of a viral molecular machine from purified protein and RNA
      constituents.
AB  - We present the assembly of the polymerase complex (procapsid) of a dsRNA virus
      from purified recombinant proteins. This molecular machine packages and
      replicates viral ssRNA genomic precursors in vitro. After addition of an external
      protein shell, these in vitro self-assembled viral core particles can penetrate
      the host plasma membrane and initiate a productive infection. Thus, a viral
      procapsid has been assembled and rendered infectious using purified components.
      Using this system, we have studied the mechanism of assembly of the common dsRNA
      virus shell and the incorporation of a symmetry mismatch within an icosahedral
      capsid. Our work demonstrates that this molecular machine, self-assembled under
      defined conditions in vitro, can function in its natural environment, the cell
      cytoplasm.

PMID- 11336708
TI  - Crystal structure of a Pumilio homology domain.
AB  - Puf proteins regulate translation and mRNA stability by binding sequences in
      their target RNAs through the Pumilio homology domain (PUM-HD), which is
      characterized by eight tandem copies of a 36 amino acid motif, the PUM repeat. We
      have solved the structure of the PUM-HD from human Pumilio1 at 1.9 A resolution.
      The structure reveals that the eight PUM repeats correspond to eight copies of a
      single, repeated structural motif. The PUM repeats pack together to form a right
      handed superhelix that approximates a half doughnut. The distribution of side
      chains on the inner and outer faces of this half doughnut suggests that the inner
      face of the PUM-HD binds RNA while the outer face interacts with proteins such as
      Nanos, Brain Tumor, and cytoplasmic polyadenylation element binding protein.

PMID- 11336709
TI  - Crystal structure at 2.8 A of an FcRn/heterodimeric Fc complex: mechanism of pH
      dependent binding.
AB  - The neonatal Fc receptor (FcRn) transports immunoglobulin G (IgG) across
      epithelia, binding IgG in acidic vesicles (pH < or = 6.5) and releasing IgG in
      the blood at pH 7.4. Well-ordered FcRn/Fc crystals are prevented by the formation
      of "oligomeric ribbons" of FcRn dimers bridged by Fc homodimers, thus we
      crystallized a 1:1 complex between rat FcRn and a heterodimeric Fc containing
      only one FcRn binding site. The 2.8 A complex structure demonstrates that FcRn
      uses its alpha2 and beta2-microglobulin domains and carbohydrate to interact with
      the Fc C(gamma)2-C(gamma)3 interface. The structure reveals conformational
      changes in Fc and three titratable salt bridges that confer pH-dependent binding,
      and can be used to guide rational design of therapeutic IgGs with longer serum
      half-lives.

PMID- 11336710
TI  - RNA editing-associated protein 1 is an RNA binding protein with specificity for
      preedited mRNA.
AB  - RNA editing in the mitochondria of kinetoplastids involves the addition and
      deletion of uridines at specific sites as directed by guide RNAs (gRNAs). Ample
      evidence shows that ribonucleoprotein (RNP) complexes carry out this
      posttranscriptional processing. One component of RNA editing complexes is REAP-1,
      a protein of previously unknown function found primarily in mRNA containing
      editing complexes. We now show that REAP-1 is an RNA binding protein and map the
      binding activity to the amino-terminal third of the protein. REAP-1 binds to
      poly(G) and single-stranded guanosine rich RNAs. Data presented here demonstrates
      that preedited RNAs are the preferred substrate for REAP-1. The results suggest a
      model in which the role of REAP-1 is to bring preedited mRNAs into the editing
      complex.

PMID- 11336711
TI  - A block to mRNA nuclear export in S. cerevisiae leads to hyperadenylation of
      transcripts that accumulate at the site of transcription.
AB  - Several factors contribute to nuclear mRNA export in Saccharomyces cerevisiae,
      including Mex67p, Mtr2p, Gle1p, Nup159p, Dbp5p, and Rip1p. Strains carrying
      mutations in these factors show rapid and dramatic nuclear accumulation of
      poly(A)(+) RNA. We have characterized two heat shock mRNAs, SSA4 and HSP104, in
      these mutant backgrounds; each transcript concentrates in a single intranuclear
      focus. Evidence suggests that it coincides with the site of transcription.
      Interestingly, all detectable SSA4 transcripts have undergone 3'-end formation,
      indicating that RNAs in the foci are no longer nascent. Poly(A) tails of the
      transcripts are also dramatically longer in all of these export mutants. Based on
      all of the data, we suggest that very early mRNA maturation events determine
      transcript export competence.

PMID- 11336712
TI  - Splicing factors SRp20 and 9G8 promote the nucleocytoplasmic export of mRNA.
AB  - We have uncovered a novel function for two members of the SR protein family in
      mRNA export. Using UV cross-linking, transient transfection, and Xenopus oocyte
      microinjection, we find that the nucleocytoplasmic shuttling proteins SRp20 and
      9G8 interact specifically with a 22-nt RNA element from the histone H2a gene to
      promote the export of intronless RNAs in both mammalian cells and Xenopus
      oocytes. Antibodies to SRp20 or 9G8 eliminate RNA binding and significantly
      inhibit the export of RNAs carrying the element from oocyte nuclei. Our
      observation that SRp20 and 9G8 can be UV cross-linked to polyadenylated RNA in
      both the nucleus and cytoplasm of HeLa cells suggests a more general role for
      these SR proteins in mRNA export.

PMID- 11336713
TI  - Three-dimensional structure of the anaphase-promoting complex.
AB  - The anaphase-promoting complex (APC) is a cell cycle-regulated ubiquitin-protein
      ligase, composed of at least 11 subunits, that controls progression through
      mitosis and G1. Using cryo-electron microscopy and angular reconstitution, we
      have obtained a three-dimensional model of the human APC at a resolution of 24 A.
      The APC has a complex asymmetric structure 140 A x 140 A x 135 A in size, in
      which an outer protein wall surrounds a large inner cavity. We discuss the
      possibility that this cavity represents a reaction chamber in which
      ubiquitination reactions take place, analogous to the inner cavities formed by
      other protein machines such as the 26S proteasome and chaperone complexes. This
      cage hypothesis could help to explain the great subunit complexity of the APC.

PMID- 11336714
TI  - Misoprostol for prevention of postpartum hemorrhage.
AB  - OBJECTIVE: To compare the effectiveness of 400 microg rectal misoprostol in 5
      cm(3) of saline with oxytocin 10 IU, i.m., in reducing bleeding during the third
      stage of labor. DESIGN: A double blind, randomized, clinical trial including 663
      women with uncomplicated vaginal delivery who received misoprostol (n=324) or
      oxytocin (n=339). MAIN OUTCOME MEASURES: Changes in hemoglobin and hematocrit
      from before to 72 h postpartum; blood loss during the third stage; duration of
      the third stage of labor; need for additional oxytocic drug; frequency of
      requisition and of administration of blood; changes in blood pressure; and
      occurrence of side effects. RESULTS: No significant differences were observed
      between groups, before and 72 h postpartum, in mean hemoglobin and hematocrit, on
      volume of blood loss and duration of third stage of labor. The incidence of
      shivering and mean temperature (P<0.01) was significantly greater among women
      receiving misoprostol than oxytocin. CONCLUSIONS: Misoprostol administered as a
      micro-enema, 400 microg in 5 ml of saline during the third stage of labor,
      appears to be as effective as oxytocin 10 IU, i.m., but misoprostol produced more
      side effects than oxytocin.

PMID- 11336715
TI  - Route of breech delivery and maternal and neonatal outcomes.
AB  - OBJECTIVE: To compare maternal and neonatal outcomes in elective cesarean vs.
      attempted vaginal delivery for breech presentation at or near term. METHODS: We
      reviewed the maternal and neonatal charts of all singleton breech deliveries of
      at least 35 weeks' gestation or 2000 g delivered between 1986 and 1997 at our
      institution. Patients delivered by elective cesarean were compared to those
      attempting a vaginal delivery. The neonatal outcomes analyzed were: corrected
      mortality; Apgar scores less than 7 at 5 min; abnormal umbilical cord blood
      gases; birth trauma; and admissions to the intensive care nursery. Maternal
      morbidity was also assessed and compared. RESULTS: Of 848 women meeting criteria
      for evaluation, 576 were delivered by elective cesarean while 272 attempted a
      vaginal delivery. Of 272 women undergoing a trial of labor, 203 (74.6%) were
      delivered vaginally, while 69 (25.4%) failed an attempt at vaginal delivery and
      underwent a cesarean. When comparing patients delivered by elective cesarean with
      those attempting a vaginal delivery, no significant differences were noted in
      neonatal outcomes. However, maternal morbidity was higher among women delivered
      by cesarean, regardless of the indications for the procedure. Similar neonatal
      and maternal results were noted when nulliparous patients were analyzed
      separately. CONCLUSIONS: Cesarean delivery of selected near-term infants
      presenting as breech is associated with increased maternal morbidity without
      corresponding improvement in neonatal outcomes.

PMID- 11336716
TI  - Assessment of fetal weight based on ultrasonic femur length after the second
      trimester.
AB  - OBJECTIVE: The ultrasonic measurement of the fetal femur length is a sensitive
      and precise variable for estimation of fetal growth and development. The
      objective of this study is to predict fetal weight in fetuses of more than 24
      weeks gestation by ultrasound measurement of the femur length. METHOD: In this
      study, pregnant mothers were identified by the criteria of normalities, such as:
      well-known LMP, regular menstrual cycles, no use of OCP for the last 3 months, no
      use of alcohol or cigarettes, no drug abuse, no history of diabetes or chronic
      HTN. Multiple gestations, congenital anomalies and still-births were excluded.
      Birth-weight measurements (adjusted for maternal age, baby's sex, parity and week
      of gestation) were taken immediately after birth. RESULT: The relation between
      fetal weight and fetal femur length has been determined by cross-sectional
      analysis of 900 normal fetuses (> or = 25 weeks gestation) using real time
      ultrasonography. Mathematical modeling of the data has demonstrated that the
      femur growth curve is non-linear beyond 24 weeks gestation. With the aid of a
      scientific calculator the data were analyzed and a simple second-grade equation
      has been derived: EFW (kg) = 0.042FL(2) (cm)+0.32FL-1.36, S.D. approximately +/
      235 g (Honarvar's Formula 2). With the use of this data, the error in estimation
      of EFW given FL is +/-235 g. CONCLUSION: This simple, new and accurate equation
      appears to be clinically reliable and easy to use and suggests that previous
      normal ultrasonic fetal femur length curves for another population may
      underestimate or overestimate normal fetal weight for the Iranian population.
      Thus, our formula is an excellent means to estimate true fetal weight.

PMID- 11336717
TI  - Brachial plexus injury and obstetrical risk factors.
AB  - OBJECTIVE: To determine whether known historical risk factors of brachial plexus
      injury differ between affected neonates and healthy controls. METHODS: The files
      of all 62 children with Erb's palsy who were diagnosed after birth were reviewed.
      The control group consisted of 124 randomly selected uninjured infants born
      within the same period. RESULTS: Compared with the control group, the mothers of
      the neonates with brachial plexus injury were found to be significantly older
      (32.1+/-5.2 years vs. 28.9+/-5.8 years, P = 0.01), and had a significantly higher
      incidence of diabetic pregnancy (69% vs. 14.5%, P = 0.001); the infants had a
      significantly higher mean birth weight (3846+/-576 g vs. 3220+/-582 g, P =
      0.0001) and higher incidence of birth weight > or = 4000 g (27% vs. 4.8%, P =
      0.0001). Two of the infants in the study group (3.2%) were born by elective
      cesarean section. CONCLUSIONS: Brachial plexus injury is associated with several
      non-predictable or preventable risk factors.

PMID- 11336719
TI  - A method for the repair of vesicovaginal fistulas.
AB  - OBJECTIVE: To determine the efficacy of the sliding layers method for repairing
      vesicovaginal fistulas caused by surgical trauma. METHOD: Twenty one women
      suffering from vesicovaginal fistulas after surgical trauma, operated on between
      1990 and 1995 using the sliding layers method, were included in an uncontrolled
      prospective study and followed 24 months after the procedure. Patient outcome was
      assessed according to subjective estimation, gynecological examination and
      objectively by instillation of diluted methylene blue to the urinary bladder.
      RESULTS: Sixteen out of 21 patients suffered vesicovaginal fistulas after being
      subjected to abdominal hysterectomy and five patients after vaginal surgery.
      Fourteen fistulas were located 5 to 10 mm over the interureteric edge, five
      fistulas were in the trigone and two fistulas were in the bladder neck region.
      Fistula size ranged from 5 to 35 mm in diameter but 72.1% of patient fistulas
      were less than 10 mm in diameter. Only one patient had a large bladder defect of
      35 mm in diameter. According to subjective estimation and objective assessment
      the overall success rate of the procedure after 2 years was 95.2%. Only one
      patient had to be subjected to a second successful attempt for fistula closure.
      CONCLUSION: The sliding layers method is a safe and reliable vaginal surgical
      approach for the repair of vesicovaginal fistulas after surgical trauma.

PMID- 11336718
TI  - Infectious complications following abdominal hysterectomy in Karachi, Pakistan.
AB  - OBJECTIVE: In this paper we studied the prevalence of post-operative infections
      after total abdominal hysterectomy in Karachi, Pakistan and their associated risk
      factors. METHOD: A retrospective analysis was conducted by reviewing the case
      notes of 827 consecutive total abdominal hysterectomies. RESULTS: The post
      operative infection rate was 22%. Of the patients, 6% (49) developed operative
      site infections including wound and vaginal cuff infections and pelvic abscesses
      while 16% (133) developed non-operative site infections including urinary tract
      infections and thrombophlebitis. Six risk factors were found to be significantly
      associated with post-operative infections: a pre-operative hospitalization of
      more than 2 days (P<0.02); additional non-gynecological procedures performed
      intra-operatively (P<0.02); indwelling catheterization for more than 7 days
      (P<0.001); patient's age greater than 50 years (P<0.02); an underlying malignancy
      (P<0.0001); and developing a hematoma post-operatively (P<0.04). CONCLUSION: The
      results of this study may serve as a baseline for future comparison and indicate
      interventions which may contribute to a reduction in the post-operative infection
      rate.

PMID- 11336720
TI  - Cervical cancer detection by hybrid capture and evaluation of local risk factors.
AB  - The city of Recife, northeastern Brazil, is reported to have the highest
      incidence of cervical cancer worldwide (83.2/100000 women). OBJECTIVE: To
      evaluate the efficacy of Hybrid Capture I (HC I) in cervical cancer detection and
      some risk factors in Recife. METHOD: Cervical scrapes for HC I analysis followed
      by colposcopy were collected from 140 women (70 with cervical cancer and 70 with
      normal cervix) from three screening services in Recife. RESULT: HC I sensitivity
      and specificity were 82.9 and 41.4%, respectively. The odds ratios for cervical
      cancer when Gesta > or = 5 and vaginal parity > or = 4 were, respectively, 5.30
      and 4.27. CONCLUSION: HC I is a moderately sensitive method to detect cervical
      cancer, but it does not seem to be useful as a primary screening tool for it's
      low specificity. Early pregnancy, high Gesta/Para and living in rural areas were
      important local risk factors.

PMID- 11336721
TI  - Physicians' perceptions of menopause and prescribing practices in Morocco.
AB  - OBJECTIVE: To investigate the prescribing practices of Moroccan physicians around
      menopause. METHODS: A survey was carried out on a representative sample of
      physicians in the capital city Rabat. The sample included general practitioners,
      gynecologists, cardiologists and rheumatologists, practicing in both public and
      private facilities. The instrument consisted of close- and open-ended questions
      about the socio-demographic characteristics of physicians, their patient
      population, their prescribing practices, and their perceptions of menopause and
      the different medical approaches to managing the symptoms and risks associated
      with it. RESULTS: Most of the physicians interviewed are positively inclined
      towards the notion of prevention and in favor of hormonal treatment, and
      approximately half report that they have prescribed hormone therapy.
      Gynecologists and male physicians prescribe hormones more frequently, as well as
      physicians who are at private facilities. These findings are discussed in
      relation to the physicians' perceptions of the menopause transition. CONCLUSION:
      There are considerable variations in prescribing practices and perceptions of
      menopause among Moroccan physicians.

PMID- 11336722
TI  - Socio-demographic and reproductive characteristics of women who default from
      orthodox obstetric care in Calabar, Nigeria.

PMID- 11336723
TI  - Three-dimensional prenatal ultrasound study of a large sacrococcygeal teratoma.

PMID- 11336724
TI  - Obstetric fistulae: incidence estimates for sub-Saharan Africa.

PMID- 11336725
TI  - Identification of 'vagino-anorectal reflex'.

PMID- 11336726
TI  - The management of severely malformed newborn infants: the case of conjoined
      twins.
AB  - The birth of 'Siamese' twins in August 2000 whose parents refused to consent to
      surgery for separation required English courts to decide whether the twins could
      lawfully be separated despite that refusal when one twin would certainly die as a
      direct surgical result. The Court of Appeal unanimously upheld the trial judge's
      decision to authorize surgery, taking account of principles of family law,
      criminal law and human rights law. Parental duties to the viable twin were found
      consistent with the justification of allowing, without intending, natural death
      of the non-viable twin. The right to human dignity of both twins supported the
      justification of separation surgery. The decision did not elevate physicians'
      choices over parents', but subjected both to the law. The hospital was found
      entitled to bring the case to court, but not obliged; it could have declined
      surgery in conformity with the parents' wishes.

PMID- 11336728
TI  - Pregnancy outcome in women with morbid obesity.
AB  - OBJECTIVE: To study the effects of morbid obesity defined as a first trimester
      maternal body mass index of >40 on the perinatal outcome. METHODS: One hundred
      and eighty-eight singleton pregnancies of women with first trimester BMI >40 who
      delivered at Al-Mafraq Hospital, Abu Dhabi during 1996-1998 were studied. A
      control group of normal body mass index matched for age and parity were selected
      and the perinatal variables were compared between groups. Morbidly obese women
      with diabetes and hypertension antedating the index pregnancy were later excluded
      and the data were re-analyzed. RESULTS: Morbidly obese women were noted to have
      significantly adverse perinatal outcomes including hypertensive disorders of
      pregnancy (28.8 vs. 2.9%, P<0.0001), gestational diabetes (24.5 vs. 2.2%,
      P<0.0001), cesarean section (15.2 vs. 9.3%, P<0.05) and macrosomia (32.6 vs.
      9.3%, P<0.001) compared to non-obese women. However, we noted a significantly
      lower rate of prematurity in the obese group (0.5 vs. 5.3%, P<0.001). Even when
      morbidly obese women with (a) diabetes and hypertension antedating the index
      pregnancy and (b) those who developed gestational diabetes and/or pregnancy
      induced hypertension during the index pregnancy were excluded from the analysis,
      significant differences in the perinatal outcomes still persisted. CONCLUSION:
      Morbid obesity appears to be an independent risk factor for adverse perinatal
      outcome.

PMID- 11336729
TI  - Spectral analysis of fetal heart rate variability as a predictor of intrapartum
      fetal distress.
AB  - OBJECTIVE: To evaluate the usefulness of power spectral analysis on fetal heart
      rate variability as a new diagnostic method of fetal distress. STUDY DESIGN:
      Among 76 pregnant women who underwent computerized electronic fetal monitoring
      and cord blood gas analysis, we divided them into three groups: normal fetus
      group (36); presumed distress group (26); and acidemic distress group (14). In
      order to perform linear analysis on the raw data of the fetal heart rate, after
      resampling, we performed Fourier transformation and investigated power
      distributions among very low frequency (VLF), low frequency (LF), high frequency
      (HF) bands, and autonomic balance (LF/HF). RESULTS: The results of the spectral
      analysis showed that in normal fetus group, the difference in the distribution of
      power spectrums of VLF, LF and HF was significantly higher than in presumed
      distress group and acidemic distress group. In fetal distress, the LF and VLF
      value (< or = 0.0023, > or = 0.0437) were good predictors (sensitivity 97.5%,
      75.0% and specificity 86.1%, 94.4%). The LF value (< or = 0.0013) was a good
      predictor in fetal acidemia (sensitivity 97.5% and specificity 86.1%).
      CONCLUSIONS: A computerized spectral analysis of fetal heart rate variation is a
      good predictor of fetal distress, which is made automatically and objectively.

PMID- 11336730
TI  - Evaluation of fetal femur length to detect Down syndrome in a Thai population.
AB  - OBJECTIVE: To assess the value of femur length shortening for prenatal detection
      of Down syndrome in a Thai population. METHOD: A prospective study was performed
      by experienced perinatologists on 3137 women undergoing second-trimester
      amniocentesis, between 16 and 24 weeks of gestation, for the indications of
      advanced maternal age and past history of chromosomal abnormality. Biparietal
      diameter and femur length measurements were obtained before the procedures.
      Regression equations relating biparietal diameter to femur length were used to
      calculate observed femur length/expected femur length ratio in the chromosomally
      normal and Down syndrome fetuses. Sensitivity, specificity, false-positive rate
      and likelihood ratio of a positive test result at various observed femur
      length/expected femur length ratios for detection of Down syndrome were
      calculated. A receiver-operator characteristic curve was used to determine
      threshold screening ratio. RESULTS: There were 3084 chromosomally normal
      pregnancies, 26 fetuses with Down syndrome (1:118), and 27 other chromosomal
      abnormalities. The relationship between femur length and biparietal diameter
      (BPD) was: expected femur length=-7.631+0.814 BPD, R(2)=0.78, P<0.001). Femur
      length in Down syndrome fetuses was significantly shorter than in normal fetuses
      (P<0.001). A ratio of 0.91 for observed femur length/expected femur length
      yielded a sensitivity of 42.3%, specificity of 86.2%, false positive rate of
      13.8% and likelihood ratio of a positive test result of 3.07 (95% CI 1.94-4.84)
      for detection of Down syndrome. CONCLUSIONS: In this study, femur length
      shortening in the second trimester appears to be a useful screening parameter for
      fetal Down syndrome in a Thai population.

PMID- 11336732
TI  - Fetal dysmorphism in spontaneous abortions in a Mexican population.
AB  - OBJECTIVE: The purpose of this research was to find out the frequency and type of
      fetal dysmorphism in spontaneous abortions among the Mexican population. METHOD:
      A prospective study was carried out in all the cases of spontaneous miscarriages
      occurring at the 'Dr. Manuel Gea Gonzalez' General Hospital in Mexico City, from
      July 1989 to June 1999. RESULT: Two hundred and one empty sacs and 1555 well
      defined embryos or fetuses were analyzed. Dysmorphism was observed in 48% of the
      cases, malformations being the most frequently found. Among malformations the
      largest group corresponded to morphological alterations not recognized in the
      postnatal life, facial clefts and closure defects of the abdominal wall were the
      known malformations of the postnatal period most frequently found. The most
      common syndromic entities were suggestive of bone dysplasia and Turner phenotype.
      CONCLUSION: The frequency of fetal dysmorphism in spontaneous abortions is higher
      than in newborns. Its diagnosis is very important for genetic counseling.

PMID- 11336731
TI  - Investigation of the uterine cavity and fallopian tubes using three-dimensional
      saline sonohysterosalpingography.
AB  - OBJECTIVE: To compare three-dimensional saline sonohysterosalpingography (SHSG)
      to X-ray hysterosalpingography (HSG) for the evaluation of the uterine cavity and
      fallopian tubes. PATIENT POPULATION: Fifteen infertile women on whom X-ray HSG
      had been performed within 1 year prior to this study. METHOD: Fifteen infertile
      women underwent three-dimensional power Doppler examination of the uterus and
      fallopian tubes with three-dimensional SHSG during the follicular phase.
      Distension was achieved using sterile saline injected through a 5 French HSG
      catheter. Peritoneal accumulation of free fluid surrounding the ovary and tube
      was required for a diagnosis of a patent tube. Fluid accumulation in the cul-de
      sac without visualization of the tubes was considered consistent with at least
      one tube being patent. RESULTS: three-dimensional saline SHSG was completed in 14
      patients. One patient had cervical stenosis and the procedure could not be
      performed. No significant intrauterine pathology was identified by either X-ray
      HSG or sonography. Three-dimensional saline SHSG made false positive diagnoses of
      tubal occlusion in four out of seven fallopian tubes (57%). The sensitivity and
      specificity for detecting tubal occlusion was 75 and 83%, respectively, with a
      positive predictive value of 40% and negative predictive value of 95%. Detection
      of fallopian tube architecture was not possible with three-dimensional saline
      SHSG in any patient. Simultaneous use of three-dimensional Doppler did not
      clearly identify the flow of saline through the fallopian tubes. CONCLUSIONS:
      Transvaginal three-dimensional saline SHSG provides good visualization of the
      uterine cavity and myometrial walls in three orthogonal planes. However, it does
      not diagnose tubal occlusion or depict architecture of the fallopian tube as
      accurately as X-ray HSG. Although we were able to visualize the distal fallopian
      tube and fimbria with real-time imaging, we were not able to satisfactorily image
      the proximal tube with three-dimensional power Doppler. This technique may be
      reserved as an initial screening test to evaluate the uterine cavity and test
      patency. Patients at high risk for tubal disease by history or with suspected
      tubal occlusion on three-dimensional saline SHSG should be evaluated by either X
      ray HSG or laparoscopy with chromopertubation. Further improvements of three
      dimensional technology and contrast materials will, it is hoped, make this method
      comparable to X-ray HSG.

PMID- 11336733
TI  - An international survey of practice variation in the use of antibiotic
      prophylaxis in cesarean section.
AB  - OBJECTIVE: To examine the use of antibiotic prophylaxis in cesarean section in
      different countries and in relation to a reference regimen. METHOD: Fifty
      consecutive cesarean sections performed in eight centers in five countries were
      surveyed. Data from each center were compared to a regimen recommended by the
      Cochrane Collaboration (one dose of ampicillin or cefazolin administered to all
      women shortly before the procedure or immediately after cord clamping) using
      logistic regression with adjustment for procedure type. RESULT: Prophylaxis was
      used widely, but only four centers administered prophylaxis to all women.
      Ampicillin and cefazolin were the principal antibiotics used, but broad-spectrum
      agents and multidrug regimens were also used commonly. Only two centers reliably
      administered the antibiotic at the appropriate time. The majority of women
      received only one dose of antibiotic in only three centers. CONCLUSION: The use
      of antibiotic prophylaxis in cesarean section was variable and often at odds with
      published recommendations.

PMID- 11336734
TI  - Vesicovaginal fistula treated with fibrin glue.
AB  - We report here a case of vesicovaginal fistula, following radiation therapy and
      intensive local chemotherapy for recurrent endometrial cancer of the vaginal
      stump, which was ameliorated with fibrin glue. The procedure temporarily
      postponed urinary diversion until the recurrence of irreparable fistula more than
      4 years after the development of the first vesicovaginal fistula.

PMID- 11336735
TI  - Prenatal diagnosis of twin-twin transfusion syndrome complicated with hydrops
      fetalis at 14 weeks of gestation.
AB  - Twin-twin transfusion syndrome (TTTS) may complicate multiple pregnancy.
      Monochorionic discordant twins with oligohydramnios and polyhydramnios may be
      diagnostic. Hydrops fetalis is particularly ominous. All the signs can appear
      independently at any stage of gestation. However, TTTS with hydrops fetalis in
      early pregnancy is rare. We report here a case of TTTS complicated with hydrops
      fetalis diagnosed at 14 weeks of gestation. Our case may be one of the earliest
      cases of the prenatal diagnosis of TTTS complicated with hydrops fetalis in the
      literature.

PMID- 11336736
TI  - Role of maternal oral hydration in increasing amniotic fluid volume in pregnant
      women with oligohydramnios.

PMID- 11336737
TI  - HELLP syndrome and postpartum corticosteroids.

PMID- 11336738
TI  - Cervical laceration associated with misoprostol induction.

PMID- 11336739
TI  - The interplay between ethnicity and free access to perinatal care.

PMID- 11336740
TI  - Vaginal reconstruction by McIndoe technique with a vaginal expander mold.

PMID- 11336741
TI  - Modification of vasomotor symptoms after various treatment modalities in the
      postmenopause.

PMID- 11336742
TI  - Contraceptive use among Kuwaitis, 1984-1999.

PMID- 11336743
TI  - Readability of education materials and informed consent forms for women seeking
      surgical sterilization.

PMID- 11336744
TI  - Psychological stress and spontaneous abortion.

PMID- 11336745
TI  - Biochemical characterisation of a hydrophobic ligand binding protein from the
      tapeworm Hymenolepis diminuta.
AB  - The cestode Hymenolepis diminuta contains an abundant, cytoplasmic, hydrophobic
      ligand, binding protein (H-HLBP). Studies with polarity sensitive probes suggest
      a single hydrophobic binding site, the results also indicate that the single
      tryptophan in the molecule (Trp41) is involved in ligand binding. Of the possible
      physiological ligands tested, only haematin and retinoids (retinol and retinoic
      acid) show appreciable binding in addition to fatty acids. H-HLBP also binds a
      range of anthelmintics, again with K(D) values in the nM range. The interaction
      of anthelmintics with hydrophobic binding proteins may be important in
      determining drug specificity and site of action and could have a role in the
      development of drug resistance.

PMID- 11336746
TI  - Characterisation of carbonic anhydrase in Plasmodium falciparum.
AB  - Here we report the existence, purification and characterisation of carbonic
      anhydrase in Plasmodium falciparum. The infected red cells contained carbonic
      anhydrase approximately 2 times higher than those of normal red cells. The three
      developmental forms of the asexual stages, ring, trophozoite and schizont were
      isolated from their host red cells and found to have stage-dependent activity of
      the carbonic anhydrase. The enzyme was purified to homogeneity from the crude
      extract of P. falciparum using multiple steps of fast liquid chromatographic
      techniques. It had a Mr of 32 kDa and was active in a monomeric form. The human
      red cell enzyme was also purified for comparison with the parasite enzyme. The
      parasite enzyme activity was sensitive to well-known sulfonamide-based inhibitors
      of both bacterial and mammalian enzymes, sulfanilamide and acetazolamide. The
      kinetic properties and the amino terminal sequences of the purified enzymes from
      the parasite and host red cell were found to be different, indicating that the
      purified protein most likely exhibited the P. falciparum carbonic anhydrase
      activity. In addition, the enzyme inhibitors had antimalarial effect against in
      vitro growth of P. falciparum. Moreover, the vital contribution of the carbonic
      anhydrase to the parasite survival makes the enzyme an attractive target for
      therapeutic evaluation.

PMID- 11336747
TI  - Comparison between lead accumulation of Pomphorhynchus laevis
      (Palaeacanthocephala) in the intestine of chub (Leuciscus cephalus) and in the
      body cavity of goldfish (Carassius auratus auratus).
AB  - This experimental study assessed the role of the microhabitat in the uptake of
      metals by adult acanthocephalans. We examined the accumulation of lead by adult
      Pomphorhynchus laevis in the intestine of chub (Leuciscus cephalus) and compared
      it with that in goldfish, Carassius auratus auratus, in which the parasites
      penetrate the intestinal wall and enter the body cavity. Chub and goldfish
      experimentally infected with adult Pomphorhynchus laevis were exposed to 0.01 mg
      l(-1) Pb(2+) over 3 weeks. Lead was rapidly accumulated in the intestinal
      acanthocephalans reaching a mean concentration of 7.3 microg g(-1). This
      concentration was significantly greater than in the host muscle, liver and
      intestine and more than 730 times higher than the exposure concentration.
      Intraperitoneal P. laevis in goldfish exposed to lead did not accumulate the
      metal. Thus, it was conclusively shown that metal accumulation in
      acanthocephalans is associated with the intestinal location and does not occur in
      the body cavity.

PMID- 11336748
TI  - HLA class II antigens positively and negatively associated with hepatosplenic
      schistosomiasis in a Chinese population.
AB  - To identify possible associations between host genetic factors and the onset of
      liver fibrosis following Schistosoma japonicum infection, the major
      histocompatibility class II alleles of 84 individuals living on an island
      (Jishan) endemic for schistosomiasis japonica in the Poyang Lake Region of
      Southern China were determined. Forty patients exhibiting advanced
      schistosomiasis, characterised by extensive liver fibrosis, and 44 age and sex
      matched control subjects were assessed for the class II haplotypes HLA-DRB1 and
      HLA-DQB1. Two HLA-DRB1 alleles, HLA-DRB1*0901 (P=0.012) and *1302 (P=0.039), and
      two HLA-DQB1 alleles, HLA-DQB1*0303 (P=0.012) and *0609 (P=0.037), were found to
      be significantly associated with susceptibility to fibrosis. These associated
      DRB1 and DQB1 alleles are in very strong linkage disequilibrium, with DRB1*0901
      DQB1*0303 and DRB1*1302-DQB1*0609 found as common haplotypes in this population.
      In contrast, the alleles HLA-DRB1*1501 (P=0.025) and HLA-DQB1*0601 (P=0.022) were
      found to be associated with resistance to hepatosplenic disease. Moreover, the
      alleles DQB1*0303 and DRB1*0901 did not increase susceptibility in the presence
      of DQB1*0601, indicating that DQB1*0601 is dominant over DQB1*0303 and DRB1*0901.
      The study has thus identified both positive and negative associations between HLA
      class II alleles and the risk of individuals developing moderate to severe liver
      fibrosis following schistosome infection.

PMID- 11336749
TI  - CD8+ T lymphocytes protect SCID mice against Encephalitozoon cuniculi infection.
AB  - Microsporidia are obligate intracellular parasites that cause opportunistic
      infections in immunocompromised patients. The role of two main T cell subsets in
      anti-microsporidial immunity has been studied using an Encephalitozoon cuniculi
      severe combined immunodeficient (SCID) mouse model. Whereas SCID mice
      reconstituted with CD4+ T lymphocyte-depleted naive BALB/c splenocytes resolved
      the infection, adoptive transfer of CD8+ T cell-depleted splenocytes failed to
      protect the animals against a lethal E. cuniculi infection. Splenocytes from E.
      cuniculi-immune mice specifically killed syngeneic infected macrophages in a
      short-term 51Cr-release assay. These results suggest the crucial role of
      cytotoxic T lymphocytes in the protection against E. cuniculi infection.

PMID- 11336750
TI  - Differential gene expression in haemocytes of the snail Biomphalaria glabrata:
      effects of Schistosoma mansoni infection.
AB  - Parasite encapsulation and destruction in Biomphalaria glabrata has been shown to
      involve the cellular component of the snail's internal defence system, the
      haemocytes. To identify genes involved in the immunobiology of these cells, we
      used the method of differential display reverse transcriptase polymerase chain
      reaction (DDRT-PCR) to investigate differential gene regulation in haemocytes
      isolated from Schistosoma mansoni exposed and unexposed snails. RNA isolated from
      circulating haemocytes from resistant snails (BS-90 stock), previously exposed to
      S. mansoni, was analysed using 12 different arbitrary primers in conjunction with
      an anchored Oligo d(T(11)CG) primer. Transcription profiles between haemocytes of
      parasite exposed and unexposed snails were compared and a total of 87
      differentially regulated bands were identified and isolated. Of these, 65 bands
      were cloned and used as probes in Southern blots to show the presence of
      corresponding sequences in the snail genome. RT-PCR was performed to verify the
      regulation of these transcripts. DNA sequence analysis showed that the majority
      of the cloned sequences were novel, although a few showed a high degree of
      sequence similarity to other sequences in the DNA and protein databases. One of
      these included a differentially expressed transcript that showed a significant
      degree of sequence identity to E. coli transposase Tn5, an enzyme whose activity
      is normally associated with generating mobility and instability in the genome.

PMID- 11336751
TI  - Origin and evolution of African Polystoma (Monogenea: Polystomatidae) assessed by
      molecular methods.
AB  - Among Polystomatidae (Monogenea), the genus Polystoma, which mainly infests
      neobatrachian hosts, is the most diverse and occurs principally in Africa, from
      where half the species have been reported. Previous molecular phylogenetic
      studies have shown that this genus originated in South America, and later
      colonised Eurasia and Africa. No mention was made on dispersal corridors between
      Europe and Africa or of the origin of the African Polystoma radiation. Therefore,
      a molecular phylogeny was inferred from ITS1 sequences of 21 taxa comprising two
      species from America, seven representatives from Europe and 12 from Africa. The
      topology of the phylogenetic tree reveals that a single event of colonisation
      took place from Europe to Africa and that the putative host carrying along the
      ancestral polystome is to be found among ancestral pelobatids. Percentage
      divergences estimates suggest that some presumably distinct vesicular species in
      unrelated South African anurans and some neotenic forms found in several distinct
      hosts in Ivory Coast, could, in fact, belong to two single polystome species
      parasitising divergent hosts. Two main factors are identified that may explain
      the diversity of African polystomes: (i), we propose that following some degree
      of generalism, at least during the juvenile stages of both hosts and parasites,
      distinctive larval behaviour of polystomes engenders isolation between parasite
      populations that precludes sympatric speciations; (ii), cospeciation events
      between Ptychadena hosts and their parasites are another factor of
      diversification of Polystoma on the African continent. Finally, we discuss the
      systematic status of the Madagascan parasite Metapolystoma, as well as the
      colonisation of Madagascar by the host Ptychadena mascareniensis.

PMID- 11336752
TI  - Molecules, morphology and morphometrics of Cainocreadium labracis and
      Cainocreadium dentecis n. sp. (Digenea: Opecoelidae) parasitic in marine fishes.
AB  - Molecular, morphological and morphometric analyses were conducted on several
      samples of Cainocreadium labracis (Opecoelidae), a trematode parasitic in marine
      teleosts. The samples were isolated from several specimens of Dicentrarchus
      labrax, the type host, and Dentex dentex. The molecular analysis of complete
      Internal Transcribed Spacer sequences of ribosomal DNA revealed that specimens
      isolated from each host species form two well-defined groups, whose sequence
      divergence reaches 7.5%. The morphological study showed that the two groups can
      be distinguished by several characters, including the level of maximum body
      breadth, the relative position of the testes, the shape of the cirrus pouch, and
      the extent of the uterus. Multivariate analyses of morphometrics demonstrated
      consistency of most of the characters for discriminating the two groups. Our
      results show that C. labracis specimens isolated from D. labrax and D. dentex
      represent clearly distinct entities from molecular, morphological and statistical
      points of view, which has enabled us to describe a new species, Cainocreadium
      dentecis n. sp.

PMID- 11336753
TI  - Phylogenetic relationships among rodent Eimeria species determined by plastid
      ORF470 and nuclear 18S rDNA sequences.
AB  - Phylogenetic analyses for 10 rodent Eimeria species from different host genera
      based on plastid ORF470 and nuclear 18S rDNA sequences were done to infer the
      evolutionary relationships of these rodent Eimeria species and their correlation
      to morphology and host specificity. The phylogenies based on both data sets
      clearly grouped the 10 rodent Eimeria species into two major lineages, which
      reflect more their morphological differences than host specificity. Species in
      lineage A have spheroidal to subspheroidal sporulated oocysts, are similar in
      size (18-29 x 17-23; xbar = 22 x 20 microm), have an oocyst residuum and one-two
      polar granules; these include Eimeria albigulae (Neotoma), Eimeria arizonensis
      (Peromyscus, Reithrodontomys), Eimeria onychomysis (Onychomys) and Eimeria reedi
      (Perognathus). Species in lineage B, including Eimeria falciformis (Mus), Eimeria
      langebarteli (Reithrodontomys), Eimeria nieschulzi (Rattus), Eimeria papillata
      (Mus), Eimeria separata (Rattus) and Eimeria sevilletensis (Onychomys) have
      different shapes (ovoid, ellipsoid, elongated ellipsoid, etc.), differ greatly in
      size (10-27 x 9-24; xbar = 19 x 16 microm) and all lack an oocyst residuum. Thus,
      The oocyst residuum was the most determinant feature that differentiated the two
      lineages. The accession numbers of ORF470 of E. albigulae, E. arizonensis, E.
      falciformis, E. nieschulzi, E. onychomysis, E. papillata, E. reedi, E. separata,
      E. sevilletensis, E. langebarteli are AF311630-AF311639 and 18S rDNA of E.
      langebarteli, E. papillata, E. reedi, E. separata, E. sevilletensis are AF311640
      AF311644.

PMID- 11336754
TI  - Selection of different genotype larvae and adult worms for anthelmintic
      resistance by persistent and short-acting avermectin/milbemycins.
AB  - To understand the factors that influence selection for anthelmintic resistance,
      it is necessary to examine the impact of drug treatment, particularly persistent
      drugs, on all phases of the worm life cycle. The efficacy of various
      avermectin/milbemycin anthelmintics was determined against resident worms,
      incoming larvae (L3) and development of eggs in faecal culture. Homozygote
      resistant and maternal and paternal F1-heterozygote genotypes of Haemonchus
      contortus were used to infect sheep before or after treatment with ivermectin
      (IVM) oral, IVM capsule, moxidectin (MOX) oral or MOX injectable. Total worm
      count and quantitative larval culture were used to determine efficacy against
      parasitic and free-living stages, respectively. Selection for resistance by IVM
      capsules occurred at the adult and L3 stages because of poor efficacy against
      these stages for all resistant genotypes. However, the selective advantage of
      these surviving worms was reduced due to the low development of their eggs to L3
      in faecal culture. For MOX, selection for resistance predominantly occurred after
      treatment because of high efficacy against resident adult worms of all resistant
      genotypes but poor efficacy against resistant L3 ingested after drug
      administration. The results indicated no evidence of sex-linked inheritance for
      IVM resistance. Mean IVM efficacies against homozygous and heterozygous resistant
      adult worms were not different, and IVM capsule efficacy against incoming L3 was
      approximately 70% for all resistant genotypes, consistent with a dominant trait.
      MOX was highly effective against adults of all resistant genotypes and
      approximately 76% effective against incoming L3 regardless of resistance
      genotype, also consistent with a dominant trait. These results will enable the
      impact of persistent drugs on worm control and anthelmintic resistance to be
      estimated. The results indicate that IVM capsules should not be used in
      populations where avermectin/milbemycin resistance is present.

PMID- 11336755
TI  - Early immunodiagnosis of fasciolosis in ruminants using recombinant Fasciola
      hepatica cathepsin L-like protease.
AB  - A diagnostic ELISA with recombinant Fasciola hepatica cathepsin L-like protease
      as antigen was developed to detect antibodies against F. hepatica in sheep and
      cattle. The recombinant cathepsin L-like protease was generated by functional
      expression of the cDNA from adult stage F. hepatica flukes in Saccharomyces
      cerevisiae. Specificity and sensitivity of the cathepsin L enzyme-linked
      immunosorbent assay (ELISA) was assessed using sera from sheep and calves
      experimentally or naturally mono-infected with F. hepatica and six-seven other
      parasites. The sensitivity of the cathepsin L ELISA for sheep and cattle sera was
      99.1 and 100%, respectively. In the experimental setting with established mono
      infections, the specificity of the cathepsin L ELISA was 98.5% for cattle sera
      and 96.5% for sheep sera. In experimentally infected cattle and sheep, the first
      detection of F. hepatica-specific antibodies appeared first between 5 and 7 weeks
      post-infection, but depended on the infectious dose of F. hepatica. In ELISA the
      detection preceded first detection of the infection based on egg counts and
      remained detectable till at least 23 weeks after a primary F. hepatica infection.
      Detection of Fasciola gigantica infections was similar to detection of F.
      hepatica. The first detection occurred at week 5 and signals persisted for at
      least 20 weeks. All sera from naturally F. hepatica infected sheep were
      seropositive in the cathepsin L-like ELISA. The relevance of this ELISA format
      was also evaluated using sera from naturally infected cattle in the Netherlands,
      Ecuador and Vietnam and compared with results from egg-counts. For the latter two
      endemic areas with mixed parasitic infections the 'apparent' sensitivity of the
      cathepsin L ELISA was calculated for all serum samples together to be 90.2%. The
      'apparent' specificity under these conditions was calculated to be 75.3%. In
      cattle, the cathepsin L ELISA was superior to the concurrently evaluated peptide
      ELISA format using a single epitope as the antigen both in controlled natural
      infections as well as in infections in endemic areas. The present ELISA-format
      contributes a relatively sensitive and reliable tool for the early serodiagnosis
      of bovine and ovine fasciolosis.

PMID- 11336756
TI  - Molecular markers for gyrodactylids (Gyrodactylidae: Monogenea) from five fish
      families (Teleostei).
AB  - Thirty-one gyrodactylid species from five families of freshwater fish were
      examined and variable region V4 of the 18S small subunit ribosomal RNA gene and
      ribosomal RNA internal transcribed spacers ITS1 and ITS2 were sequenced. Both the
      V4 region and spacers ITS1 and ITS2 proved useful for gyrodactylid diagnosis.
      Sequences of these fragments exhibited interspecific variations and allowed clear
      determination at the species level. In some cases, the length of the ITS1 PCR
      fragment provided useful genetic markers. Species that yielded a short ITS1
      fragment also showed distinct groupings in ITS2 and V4 sequences that were
      markedly different to sequences from species that contain a long ITS1. Repetitive
      sequences located in the ITS1 of Gyrodactylus gobii and Gyrodactylus vimbi
      accounted for some of the variations in length of PCR products. There was no
      evidence for intraspecific variation within these regions and short tandem
      repeats were not found in the other species studied. The number of polymorphic
      and intraspecific variations in nucleic acid sequences was low, therefore these
      variations did not affect species determination of gyrodactylids. Minor
      differences in the sequences between Western and Eastern European populations
      were detected for Gyrodactylus salaris/Gyrodactylus thymalli, Gyrodactylus
      teuchis and Gyrodactylus truttae, but these do not affect species diagnosis based
      on ribosomal DNA sequence. These results confirm the utility of both variable
      region V4 and the ITS as molecular markers for Gyrodactylus species.

PMID- 11336757
TI  - Pregnancy complicated by chronic spinal cord injury and history of autonomic
      hyperreflexia.
AB  - BACKGROUND: Women with spinal cord injuries are at risk for autonomic
      hyperreflexia during labor. CASE: A 36-year-old woman, gravida 4, para 2, abortus
      1, with a spinal cord injury and a positive antibody screen result had had a
      previous pregnancy complicated by autonomic hyperreflexia during labor. Autonomic
      hyperreflexia did not occur during serial amniocenteses and fetal transfusions
      for isoimmunization or intrapartum. CONCLUSION: Intrauterine procedures and
      vaginal delivery were accomplished without autonomic hyperreflexia in this
      pregnancy. Intrauterine procedures and vaginal delivery might be done safely in
      women with histories of autonomic hyperreflexia.

PMID- 11336758
TI  - Spontaneous intracranial hypotension during pregnancy.
AB  - BACKGROUND: Spontaneous intracranial hypotension is characterized by postural
      headache associated with low cerebrospinal fluid pressure. CASE: A 37-year-old
      Japanese woman, gravida 3, para 2, had sudden onset of severe postural headache
      at 8 weeks' gestation, accompanied by nausea and vomiting. Results of medical and
      neurologic examinations were normal, and there was no measurable cerebrospinal
      fluid pressure on lumbar puncture. Brain magnetic resonance imaging showed
      diffuse subdural fluid collection and a narrowing of the ambient cistern,
      confirming the diagnosis of spontaneous intracranial hypotension. After a month
      of bed rest and intravenous fluid infusion, all symptoms subsided gradually and
      did not recur. CONCLUSION: Obstetricians should be aware that spontaneous
      intracranial hypotension can occur in pregnancy.

PMID- 11336759
TI  - Caffeine-induced hypokalemic paralysis in pregnancy.
AB  - BACKGROUND: Excessive ingestion of caffeine can induce hypokalemia, which affects
      the neuromuscular system and can lead to paralysis. CASE: A 24-year-old woman,
      gravida 3, para 2-0-0-2 at 33 weeks' gestation presented with muscular paralysis
      and hypokalemia secondary to drinking 6 to 7 L of cola per day with little other
      oral intake. After potassium replacement and stopping caffeine ingestion, the
      symptoms resolved quickly. CONCLUSION: The physiologic changes of pregnancy might
      potentiate the effect of caffeine on serum potassium concentration.

PMID- 11336760
TI  - Combined deficiency of factors II, VII, IX, and X (Borgschulte-Grigsby
      deficiency) in pregnancy.
AB  - BACKGROUND: Combined deficiency of vitamin K-dependent coagulation factors (II,
      VII, IX, X) is an uncommon challenge for the expectant gravida. CASE: A 34-year
      old primigravida had congenital combined deficiency of factors II, VII, IX, and X
      that were incompletely sensitive to vitamin K. She had an altered form of vitamin
      K-dependent factors that retained immunologic activity but lacked coagulant
      activity and the normal complement of gamma-carboxyglutamic acid residues. She
      required vitamin K supplementation throughout her life. After an uneventful
      pregnancy she had postpartum hemorrhage resulting from an episiotomy. Fresh
      frozen plasma was administered to achieve hemostasis. The remainder of her
      postpartum course was normal. CONCLUSION: Combined congenital deficiency of
      factors II, VII, IX, and X can be managed in pregnancy with the use of vitamin K
      and fresh frozen plasma.

PMID- 11336761
TI  - Leukemia in pregnancy and fetal response to multiagent chemotherapy.
AB  - BACKGROUND: Leukemia is rare in pregnancy and treatment with intensive,
      multiagent chemotherapy produces complete remission in most adults, but might
      have deleterious effects on fetuses. CASE: A 24-year-old gravida 3 para 2
      presented at 24 weeks with pruritus, rash, pancytopenia, and hepatitis. A bone
      marrow biopsy found acute lymphocytic leukemia. She completed three cycles of
      intensive multiagent chemotherapy with transient oligohydramnios in each cycle.
      Although there was decreased fetal growth rate, umbilical artery Doppler scans
      were normal. She delivered a normal 2150-g male infant at 36 weeks. CONCLUSION:
      Pregnant women with newly diagnosed leukemia should not delay treatment, but
      multiagent chemotherapy might have transient effects on fetuses, most notably
      oligohydramnios. However, if fetal testing is normal, delivery might not be
      indicated.

PMID- 11336762
TI  - Hereditary hemorrhagic telangiectasia with pulmonary arteriovenous malformations.
AB  - BACKGROUND: Most congenital pulmonary arteriovenous malformations are associated
      with hereditary hemorrhagic telangiectasia. During pregnancy, pulmonary
      hemorrhage can occur, compromising maternal and fetal health. CASES: We studied
      three pregnancies in two women with hemorrhagic telangiectasia complicated by
      pulmonary arteriovenous malformations. A 28-year-old primigravida's fetus died at
      25 weeks' gestation, and she had embolotherapy with coil springs, which corrected
      the hypoxemic state. In a subsequent pregnancy she delivered a healthy 2315-g
      infant at 38 weeks' gestation. A 19-year-old primigravida had spontaneous
      hemothorax at 26 weeks' gestation with severe hypoxemia and a growth-restricted
      fetus without umbilical artery diastolic flow. Pulmonary arteriovenous
      malformation was diagnosed by computed tomography of the maternal lung. She had
      continued pulmonary bleeding, so emergency lung lobectomy was done. Maternal
      hypoxemia and umbilical diastolic flow improved, and she had term delivery of a
      healthy 2250-g infant. CONCLUSION: Antenatal diagnosis and treatment of women
      with hereditary hemorrhagic telangectasia and pulmonary arteriovenous
      malformations might prevent potentially life-threatening fetomaternal
      complications.

PMID- 11336763
TI  - Pregnancy with cytochrome oxidase-deficient mitochondrial myopathy.
AB  - BACKGROUND: Cytochrome oxidase-deficient mitochondrial myopathies represent a
      heterogeneous group of muscle disorders. Physical stress can cause life
      threatening risks related to rhabdomyolysis or respiratory compromise. CASE: A 21
      year-old primigravida with cytochrome C oxidase-deficient mitochondrial myopathy
      who presented for obstetric care at 8 weeks' gestation complained of muscle
      fatigue and spasm after exertion. The increased metabolic demands of pregnancy
      led to worsening pain, muscle fatigue, and ultimately complete immobility.
      CONCLUSION: Cytochrome oxidase-deficient mitochondrial myopathies are rare but
      serious complications of pregnancy.

PMID- 11336764
TI  - Breast-feeding by a cyclosporine-treated mother.
AB  - BACKGROUND: Cyclosporine is known to be excreted in breast milk, but levels in
      infants are not known. Post-transplant breast-feeding has been contraindicated in
      mothers treated with calcineurin inhibitors such as cyclosporine. CASE: A 35-year
      old woman exclusively breast-fed her infant during the first 10.5 months of life
      while she was being treated with cyclosporine. Cyclosporine measurements in
      infant and maternal blood and breast milk revealed a mean breast milk/maternal
      blood level ratio of 84%, but undetectable levels in the infant. The infant grew
      and developed normally. CONCLUSION: The infant of a cyclosporine-treated mother
      was breast-fed exclusively during the first 10.5 months of life and did not
      absorb a detectable amount of the drug. Fetal growth and development were normal.

PMID- 11336765
TI  - Endotoxemia causing fetal bradycardia during urosepsis.
AB  - BACKGROUND: Fetal bradycardia is a recognized response to maternal hypothermia
      associated with hypoglycemia, tocolysis with magnesium sulfate, or urosepsis, and
      it is thought to be a direct response to the decrease in the maternal core
      temperature. CASE: A 25-year-old white woman, gravida 1, para 0, at 31 1/7 weeks'
      gestation was admitted with a diagnosis of pyelonephritis. The baseline fetal
      heart rate was 120 beats per minute with accelerations. Within 3 hours of
      admission, the patient became hypothermic (35.1C) and, concomitantly, the fetal
      heart rate baseline declined to 90 beats per minute with marked variability.
      Despite sustained maternal hypothermia, the fetal heart rate baseline rose to 120
      beats per minute. It was another 6 hours before the patient's temperature rose
      above 38.5C. Her urine and blood cultures were positive for Serratia rubidacea
      infection. The patient delivered a healthy infant at 39 weeks' gestation.
      CONCLUSION: Fetal bradycardia in the presence of urosepsis might be due to the
      release of endotoxin from gram-negative bacteria, triggering production of
      cardiotoxic cytokines, rather than to maternal hypothermia alone.

PMID- 11336766
TI  - Fetal chylothorax response to maternal dietary treatment.
AB  - BACKGROUND: Fetal chylothorax is associated with elevated perinatal mortality.
      Development of mediastinal shift with significant lung compression before 35
      weeks' gestation needs treatment. CASE: A 24-year-old gravida 2, para 0 presented
      at 26 weeks' gestation with a fetal pleural effusion with a mediastinal shift and
      abnormal Doppler velocimetry indices in several vessels. Thoracentesis was
      successful but 3 days later, the fetal effusion had reaccumulated. Because of
      fetal position, a pleuro-amniotic shunt was difficult technically, so maternal
      medical treatment was initiated with a low-fat, high medium-chain triglyceride
      diet. After initial mild decrease, the estimated volume of the fetal chylothorax
      remained stable until 36 weeks' gestation, at which time we delivered by cesarean
      an infant with good Apgar scores. After aspiration of the remaining thoracic
      fluid and administration of a similar diet, the infant did well, with normal
      growth and development. CONCLUSION: Maternal dietary treatment might help delay
      the need for thoracentesis in cases of fetal chylothorax.

PMID- 11336767
TI  - Fetal splenic rupture following transfusion.
AB  - BACKGROUND: Splenic rupture in the newborn is a rare complication in
      erythroblastosis fetalis. There are no reports of splenic rupture in the fetus
      affected by hemolytic disease of the newborn. CASE: A 41-year-old gravida 3, para
      2-0-0-2 with severe rhesus alloimmunization was managed with serial intrauterine
      transfusions resulting in fetal death after the fourth procedure. Autopsy
      findings revealed intra-abdominal clotted blood and splenic capsular defects
      consistent with splenic rupture. CONCLUSION: Fetal splenic rupture might occur in
      hemolytic disease of the newborn associated with splenomegaly. Acute hemodynamic
      changes with increased intra-abdominal pressure from intrauterine transfusion
      might precipitate splenic rupture. (Obstet Gynecol 2001;97:824-5.

PMID- 11336768
TI  - Expectant management of intramural ectopic pregnancy.
AB  - BACKGROUND: Intramural ectopic pregnancy is unusual, difficult to diagnose, and
      associated with a high rate of uterine rupture. CASE: A 35-year-old, gravida 3,
      para 0-0-2-0 was diagnosed with intramural ectopic pregnancy by ultrasound
      showing a gestational sac surrounded completely by myometrium. It was confirmed
      by laparoscopy. With expectant management, the gestation resolved spontaneously.
      CONCLUSION: Early diagnosis by ultrasound of intramural ectopic pregnancy permits
      expectant management which, if successful, would aid in maintaining fertility.

PMID- 11336769
TI  - Acute peritonitis due to introital stenosis and perforation of a bowel neovagina
      in a transsexual.
AB  - BACKGROUND: Stenosis of the neovagina is a late postoperative complication of
      male-to-female sex reassignment surgery when patients do not have frequent sexual
      intercourse or do not perform vaginal dilation. CASE: A 39-year-old male-to
      female transsexual who had sex reassignment surgery, in which a segment of
      sigmoid colon was used for neovagina construction, developed total introital
      stenosis and subsequent peritonitis caused by bowel perforation of the colon
      conduit. CONCLUSION: To avoid stenosis of the neovagina, an inflatable silicon
      vaginal stent should be used all day for 30 days, then for 3 months overnight or
      until sexual function is regular.

PMID- 11336770
TI  - Postmenarchal development of chylous ascites in acrocephalosyndactyly with
      congenital lymphatic dysplasia.
AB  - BACKGROUND: Acrocephalosyndactyly is a syndrome characterized by congenital
      malformation of the skull with craniosynostosis, midface hypoplasia, and
      symmetrical webbed fusion of the fingers and toes. We describe a possible
      pathophysiologic mechanism for chylous ascites that developed several months
      after menarche in a woman with acrocephalosyndactyly and congenital lymphatic
      dysplasia. CASE: A 25-year-old nulligravid woman with acrocephalosyndactyly, at
      18 months after menarche, developed persistent abdominal distension at age 18
      years. Laparoscopy at age 25 years revealed chylous ascites with marked chronic
      peritoneal inflammation, and lymphatic dysplasia with lymphocysts. With hormone
      manipulation, the chylous ascites fluctuated. CONCLUSION: After menarche in a
      woman with acrocephalosyndactyly, ovarian steroid hormones might have increased
      lymph production and hydrostatic pressure, causing rupture of congenitally
      dysplastic lymph vessels resulting in chylous ascites.

PMID- 11336771
TI  - Compartment syndrome associated with lithotomy position and intermittent
      compression stockings.
AB  - BACKGROUND: Compartment syndrome is a condition in which increased tissue
      pressure within a limited tissue space compromises the circulation and function
      of the contents of the space. CASE: A 43-year-old black woman, para 3, had repair
      of a recurrent vesicovaginal fistula. She was placed in a low lithotomy position
      with thigh length sequential compression sleeves. The procedure lasted more than
      5 hours. On postoperative day 1, she complained of pain in her right leg and
      foot. Compartment syndrome was diagnosed and emergency fasciotomy was done.
      CONCLUSION: Gynecologists should be aware of the possibility of compartment
      syndrome during prolonged procedures with patients in the lithotomy position.
      Concomitant intermittent compression sleeves might further increase the risk.
      Early diagnosis and treatment of compression syndrome are essential to minimize
      long-term neurovascular morbidity.

PMID- 11336772
TI  - Diffuse uterine leiomyomatosis with ovarian and parametrial involvement.
AB  - BACKGROUND: Diffuse uterine leiomyomatosis is a rare, benign entity and
      approximately 30 cases have been described previously. CASE: A 42-year-old woman
      who complained of abdominal pain had a pelvic ultrasound scan showing a uterine
      mass. During the operation, the surgeon observed that both ovaries, the broad
      ligament, and the pelvis contained various nodules of striking size. On
      sectioning, uterus and ovaries contained multiple nodules of elastic consistency;
      microscopically, all consisted of benign smooth muscle tissue. CONCLUSION:
      Leiomyomatosis may exhibit concomitant parametrial, pelvic, and bilateral ovarian
      involvement.

PMID- 11336773
TI  - Uterine artery embolization in an undiagnosed uterine sarcoma.
AB  - BACKGROUND: Uterine sarcomas are rare malignancies that resemble benign uterine
      leiomyomata. Uterine artery embolization is offered increasingly for treatment of
      uterine leiomyomata, which might lead to embolization of undiagnosed uterine
      sarcoma. CASE: A 52-year-old woman, gravida 7, para 6, with perimenopausal
      menometrorrhagia was diagnosed with uterine leiomyomata after physical
      examination and transvaginal ultrasound. An endometrial biopsy was negative for
      malignancy. After medical treatment was unsuccessful, she had uterine artery
      embolization. She then passed a piece of tissue from her vagina, the pathology
      report of which was necrotic high-grade sarcoma. During surgery we confirmed that
      the tumor was confined to the uterus. CONCLUSION: Uterine sarcoma cannot be
      diagnosed except by pathologic examination of a resected specimen. Women
      considering uterine artery embolization for treatment of apparent leiomyomata
      should be counseled on the risk of decreased survival by delaying diagnosis and
      treatment of uterine sarcoma.

PMID- 11336774
TI  - Adenocarcinoma diagnosed at endometrial ablation.
AB  - BACKGROUND: Endometrial ablation is a surgical alternative to hysterectomy. Cases
      exist in the literature of endometrial adenocarcinoma found at endometrial
      ablation. If endometrial cancer is occult it might not be detected during
      ablation, especially if destructive techniques are used. CASE: A 41-year-old
      woman had a history of menorrhagia. A previous D&C showed benign proliferative
      endometrium. Investigations for menorrhagia found no abnormalities. The diagnosis
      was dysfunctional uterine bleeding. Endometrial ablation was done and the
      pathologic examination of the resected endometrium found focal, well
      differentiated adenocarcinoma of the endometrium. CONCLUSION: This case shows the
      importance of patient selection, evaluation, and surveillance after endometrial
      ablation. Resection of the endometrium is superior to destructive techniques
      because it provides tissue for pathologic evaluation. We recommend close
      postoperative surveillance in such cases.

PMID- 11336775
TI  - Tocolysis with nifedipine or beta-adrenergic agonists: a meta-analysis.
AB  - OBJECTIVE: To clarify the relative efficacy of nifedipine and beta-agonists for
      tocolysis. DATA SOURCES: The literature was searched in the following databases:
      MEDLINE 1965-1998, Embase 1988-1998, Current Contents 1997-1998, and the Cochrane
      Database for 1998. We also sought unpublished trials and abstracts submitted to
      major international congresses. Search terms were: "tocolysis," "nifedipine,"
      "calcium channel blocker," "ritodrine," "terbutaline," and "salbutamol." METHODS
      OF STUDY SELECTION: Randomized controlled trials comparing tocolysis with
      nifedipine and beta-adrenergic agonists during preterm labor were reviewed. In
      cases with postrandomization exclusions, authors were contacted to obtain intent
      to-treat results and to avoid analytical bias. We identified 11 published and two
      unpublished randomized trials. TABULATION, INTEGRATION, AND RESULTS: Data were
      extracted by two reviewers and analyzed by a blinded biostatistician with RevMan
      3.1 software from the Cochrane Collaboration. We analyzed nine relevant
      randomized controlled trials that included 679 patients. Meta-analysis showed
      that nifedipine was more effective than the beta-agonists in delaying delivery at
      least 48 hours [odds ratio (OR) 1.52, 95% confidence interval (CI) 1.03, 2.24],
      or over 34 weeks (OR 1.87, 95% CI 1.11, 3.15). The agents did not differ as to
      the incidence of deliveries after 37 weeks (OR 1.29, 95% CI 0.85, 1.96) or the
      neonatal mortality rate (OR 1.51, 95% CI 0.63, 3.65). Treatment with nifedipine
      was interrupted significantly less often because of side effects (OR 0.12, 95% CI
      0.05, 0.29) and led to better neonatal outcomes (fewer infants with respiratory
      distress syndrome: OR 0.57, 95% CI 0.37, 0.89) or transferred to neonatal
      intensive care units (OR 0.65, 95% CI 0.43, 0.97). CONCLUSION: With respect to
      neonatal outcome, nifedipine appears to be more effective than beta-agonists for
      tocolysis and should be considered for use as a first-line tocolytic agent.

PMID- 11336776
TI  - Dinoprostone vaginal insert for cervical ripening and labor induction: a meta
      analysis.
AB  - OBJECTIVE: To compare dinoprostone 10 mg controlled-release vaginal insert with
      other forms of vaginal or cervical prostaglandin for cervical ripening. DATA
      SOURCES: Literature search strategy included review of the Cochrane database of
      randomized trials, on-line searching of MEDLINE, hand searching of
      bibliographies, and contact with authors of relevant reports. METHODS OF STUDY
      SELECTION: Randomized trials were included if they compared a dinoprostone slow
      release vaginal insert with an alternative vaginal or cervical prostaglandin for
      cervical ripening and labor induction in women at term with singleton gestations.
      Primary end points were delivery by 24 hours postinsertion, uterine hypertonus
      with fetal heart change, and cesarean delivery rate. Study inclusion, validity
      assessment, and data extraction were carried out independently by two reviewers,
      and cross-checked for consistency. Data were combined when appropriate, using the
      Mantel-Haenszel fixed-effects method. Statistical heterogeneity was assessed
      using chi-square statistics. TABULATION, INTEGRATION, AND RESULTS: Nine relevant
      trials were identified, seven comparing the dinoprostone 10 mg vaginal insert
      with dinoprostone gel and two with misoprostol. Five trials reported adequate
      methods for randomization concealment. None were double blind. The likelihood of
      delivery by 24 hours was similar with the vaginal insert and alternatives: common
      odds ratio (OR) 0.80 (95% confidence interval [CI] 0.56, 1.15). Uterine
      hypertonus with change in fetal heart and cesarean delivery rate were also
      similar: common OR 1.19 (95% CI 0.56, 2.54) and 0.78 (95% CI 0.56, 1.08),
      respectively. The secondary end points of mean time to delivery and delivery by
      12 hours appeared to favor misoprostol-dinoprostone gel. However, data for these
      end points were heterogeneous and their combination is therefore of limited value
      and potentially misleading. CONCLUSION: No clinically significant differences
      were identified between the vaginal insert and alternatives used for cervical
      ripening at term.

PMID- 11336777
TI  - Tamoxifen treatment and gynecologic side effects: a review.
AB  - OBJECTIVE: To review the literature on tamoxifen side effects on the female
      genital tract and psychosexual function in premenopausal and postmenopausal
      women. DATA SOURCES: We used the English-language literature in MEDLINE and
      reference lists from selected articles. Search terms included: "tamoxifen and
      estrogen receptor," "transcription activation," "premenopause," "postmenopause,"
      "vaginal epithelium," "uterus," "endometrial hyperplasia," "polyps," "endometrial
      cancer," "sonography," "sonohysterography," "hysteroscopy," "myometrium,"
      "myoma," "sarcoma," "endometriosis," "ovarian cysts," "hot flushes,"
      "concentration problems," "sleep disturbance," "vaginal dryness," "sexual
      function," "libido," "dyspareunia," and "quality of life." No study-type
      restrictions were imposed. METHODS OF STUDY SELECTION: With respect to clinical
      studies we included case cohort studies, observational studies; if no trials were
      available on a subject, case reports published in peer-reviewed journals were
      selected. For the discussion on endometrial surveillance of tamoxifen users,
      letters and editorials published in peer-reviewed journals also were used.
      Subjects of interest were mechanism of action of tamoxifen, tamoxifen and the
      vaginal epithelium, endometrium, mesenchymal tumors of the uterus, ovaries,
      sexual function, and vasomotor instability. TABULATION, INTEGRATION, AND RESULTS:
      Eligible studies were analyzed to determine their usefulness in this review. Data
      from trials that evaluated tamoxifen side effects on specific genital tissues
      were combined, with special interest in differentiation of side effects in
      premenopausal and postmenopausal women. Weighted estimates of severity and extent
      of side effects were usually not possible because of lack of randomized trials.
      Only the risk of endometrial cancer in relation to tamoxifen treatment could be
      estimated. CONCLUSION: The gynecologic side effects of tamoxifen are diverse and
      reflect the complexity of its mechanism of action, with agonistic and
      antagonistic effects on various tissues, depending on the ambient estradiol
      concentration and hence menopausal status of the patient. The most frequently
      reported side effect was hot flushes, and the most worrisome gynecologic side
      effect was a two- to three-fold increased risk of endometrial cancer in
      postmenopausal women. Despite its side effects, the benefits of tamoxifen in
      controlling breast cancer or prevention of its relapse are still without debate.

PMID- 11336778
TI  - The role of MK-801 in sensitization to stimulants.
AB  - Behavioral responses to stimulants can be progressively and persistently enhanced
      by their repeated administration. This phenomenon, called behavioral
      sensitization, may underlie substance abuse, psychosis, recurrence in bipolar
      disorder, or other psychiatric problems. A growing body of work has implicated
      excitatory amino acid systems in behavioral sensitization. Most of the evidence
      for a role of excitatory amino acids has come from experiments demonstrating
      prevention of sensitization by excitatory amino acid antagonists, especially the
      noncompetitive NMDA receptor antagonist MK-801. Results of studies with MK-801
      have varied, however, leading to conflicting interpretations of its relationship
      to behavioral sensitization. This paper critically discusses the design of
      experiments that have used MK-801, and interprets data from these experiments in
      terms of the two leading explanations for the role of MK-801: 1) that
      sensitization is an example of the family of plastic events that require
      excitatory amino acid transmission or 2) that interoceptive cues associated with
      MK-801 lead to state-dependent learning that modifies sensitization because, in
      essence, the animal does not recognize the stimulant as the same drug if it is
      given in close association with MK-801. Based on conflicting reports on effects
      of MK-801, we propose 1) strategies for distinguishing components of MK-801's
      effects on responses to stimulants, 2) a model that is a hybrid of the two
      interpretations of its effects on sensitization, and 3) experimental strategies
      for testing this model.

PMID- 11336779
TI  - On the cause of mental retardation in Down syndrome: extrapolation from full and
      segmental trisomy 16 mouse models.
AB  - Down syndrome (DS, trisomy 21, Ts21) is the most common known cause of mental
      retardation. In vivo structural brain imaging in young DS adults, and post-mortem
      studies, indicate a normal brain size after correction for height, and the
      absence of neuropathology. Functional imaging with positron emission tomography
      (PET) shows normal brain glucose metabolism, but fewer significant correlations
      between metabolic rates in different brain regions than in controls, suggesting
      reduced functional connections between brain circuit elements. Cultured neurons
      from Ts21 fetuses and from fetuses of an animal model for DS, the trisomy 16
      (Ts16) mouse, do not differ from controls with regard to passive electrical
      membrane properties, including resting potential and membrane resistance. On the
      other hand, the trisomic neurons demonstrate abnormal active electrical and
      biochemical properties (duration of action potential and its rates of
      depolarization and repolarization, altered kinetics of active Na(+), Ca(2+) and
      K(+) currents, altered membrane densities of Na(+) and Ca(2+) channels). Another
      animal model, the adult segmental trisomy 16 mouse (Ts65Dn), demonstrates reduced
      long-term potentiation and increased long-term depression (models for learning
      and memory related to synaptic plasticity) in the CA1 region of the hippocampus.
      Evidence suggests that the abnormalities in the trisomy mouse models are related
      to defective signal transduction pathways involving the phosphoinositide cycle,
      protein kinase A and protein kinase C. The phenotypes of DS and its mouse models
      do not involve abnormal gene products due to mutations or deletions, but result
      from altered expression of genes on human chromosome 21 or mouse chromosome 16,
      respectively. To the extent that the defects in signal transduction and in active
      electrical properties, including synaptic plasticity, that are found in the Ts16
      and Ts65Dn mouse models, are found in the brain of DS subjects, we postulate that
      mental retardation in DS results from such abnormalities. Changes in timing and
      synaptic interaction between neurons during development can lead to less than
      optimal functioning of neural circuitry and signaling then and in later life.

PMID- 11336780
TI  - The cognitive neuroscience of sustained attention: where top-down meets bottom
      up.
AB  - The psychological construct 'sustained attention' describes a fundamental
      component of attention characterized by the subject's readiness to detect rarely
      and unpredictably occurring signals over prolonged periods of time. Human imaging
      studies have demonstrated that activation of frontal and parietal cortical areas,
      mostly in the right hemisphere, are associated with sustained attention
      performance. Animal neuroscientific research has focused on cortical afferent
      systems, particularly on the cholinergic inputs originating in the basal
      forebrain, as crucial components of the neuronal network mediating sustained
      attentional performance. Sustained attention performance-associated activation of
      the basal forebrain corticopetal cholinergic system is conceptualized as a
      component of the 'top-down' processes initiated by activation of the 'anterior
      attention system' and designed to mediate knowledge-driven detection and
      selection of target stimuli. Activated cortical cholinergic inputs facilitate
      these processes, particularly under taxing attentional conditions, by enhancing
      cortical sensory and sensory-associational information processing, including the
      filtering of noise and distractors. Collectively, the findings from human and
      animal studies provide the basis for a relatively precise description of the
      neuronal circuits mediating sustained attention, and the dissociation between
      these circuits and those mediating the 'arousal' components of attention.

PMID- 11336781
TI  - Anticancer drug resistance in primary human brain tumors.
AB  - The difficult clinical situation still associated with most types of primary
      human brain tumors has fostered significant interest in defining novel
      therapeutic modalities for this heterogeneous group of neoplasms. Beginning in
      the 1980s chemotherapy has been incorporated into the treatment protocol of a
      number of intractable brain tumors. However, it has predominantly failed to
      improve patient outcome. The unsatisfactory results with chemotherapeutic
      intervention have chiefly been attributed to tumor cell resistance. In recent
      years, there has been a literal explosion in our understanding about the
      mechanisms by which cancer cells become chemoresistant. During the course of
      their evolution (intrinsic resistance) or in response to chemotherapy (acquired
      resistance) these cells may follow a number of pathways of genetic alterations to
      possess a common (multidrug) or drug-specific (individual drug) resistant
      phenotype. Genomic aberrations, deregulation of membrane transporting proteins
      and cellular enzymes, and an altered susceptibility to commit to apoptosis are
      among the steps on the way that contribute to the genesis of chemotherapeutic
      treatment failure. Although, through the years we have come to yield information
      and inferences as to the roles that different molecular events may have in the
      resistance phenotype of cancer cells, the actual involvement of single genetic
      alterations in conferring drug resistance in primary brain tumors remains
      debatable. This uncertainty and, besides, the lack of proper drug resistance
      diagnostics, in a vicious circle, hinder the development of effective resistance
      modulation strategies. Clinical non-responsiveness to chemotherapy remains a
      formidable obstacle to the successful treatment of brain tumors and one of the
      most serious problems to be solved in the therapy of these lesions. Future
      advances in the chemotherapeutic management of these neoplasms will come with an
      improved understanding of the significance and interrelationship of the multiple
      biological systems operative in promoting resistance to this treatment modality.
      The focus of this review is to summarize current knowledge concerning major drug
      resistance-related markers, to describe their functional interaction en route to
      chemoresistance, and to discuss their implication in rendering human brain tumor
      cells resistant to chemotherapy.

PMID- 11336782
TI  - Structural and functional aspects of filamins.
AB  - Filamins are a family of high molecular mass cytoskeletal proteins that organize
      filamentous actin in networks and stress fibers. Over the past few years it has
      become clear that filamins anchor various transmembrane proteins to the actin
      cytoskeleton and provide a scaffold for a wide range of cytoplasmic signaling
      proteins. The recent cloning of three human filamins and studies on filamin
      orthologues from chicken and Drosophila revealed unexpected complexity of the
      filamin family, the biological implications of which have just started to be
      addressed. Expression of dysfunctional filamin-A leads to the genetic disorder of
      ventricular heterotopia and gives reason to expect that abnormalities in the
      other isogenes may also be connected with human disease. In this review aspects
      of filamin structure, its splice variants, binding partners and biological
      function will be discussed.

PMID- 11336783
TI  - Involvement of calcium signaling in the fibronectin-stimulated macrophage
      recognition of oxidatively damaged erythrocytes.
AB  - Macrophages recognize oxidatively damaged autologous erythrocytes, and cell
      surface fibronectin of macrophages enhances the recognition (Beppu et al., FEBS
      Lett. 295 (1991) 135-140). In the present study, mechanisms of enhanced
      macrophage recognition of oxidatively damaged erythrocytes by fibronectin were
      investigated. Monolayers of thioglycollate-induced mouse peritoneal macrophages
      with cell surface fibronectin recognized autologous erythrocytes oxidized with an
      iron catalyst ADP/Fe(3+). The macrophage recognition of the oxidized erythrocytes
      was inhibited partially by pretreatment of the macrophage monolayers with a
      Ca(2+) channel blocker (diltiazem), calmodulin inhibitors (W-7, trifluoperazine,
      chlorpromazine and dibucaine), an inhibitor of myosin light chain kinase (ML-9),
      a microfilament formation inhibitor (cytochalasin B), phospholipase A(2)
      inhibitors (4-bromophenacyl bromide, mepacrine) and cyclooxygenase inhibitors
      (indomethacin and aspirin). Monolayers of macrophages depleted of fibronectin by
      trypsinization lost the ability of recognizing oxidized erythrocytes, but
      acquired the ability when stimulated with a fibronectin-coated coverslip. The
      recognition of fibronectin-stimulated trypsinized macrophages was also inhibited
      by the above inhibitors. On treatment with Ca ionophore A23187, trypsinized
      macrophages acquired the ability to recognize oxidized erythrocytes. The
      recognition of Ca ionophore-stimulated trypsinized macrophages was inhibited by
      the above inhibitors except the Ca(2+) channel blocker. These results indicate
      that the Ca(2+) signaling including Ca(2+) influx, calmodulin activation and
      myosin light chain phosphorylation are involved in the fibronectin stimulation of
      the recognition of macrophages for oxidized erythrocytes. Involvement of
      microfilament formation and arachidonate cascade in the fibronectin stimulation
      was also suggested.

PMID- 11336784
TI  - Wnts differentially regulate colony growth and differentiation of chondrogenic
      rat calvaria cells.
AB  - The wingless- and int-related proteins (Wnts) have an important role during
      embryonic development and limb patterning. To investigate their function during
      chondrocyte differentiation, we used NIH3T3 cells producing seven members of the
      Wnt family and secreted frizzled-related protein (sFRP-2) for co-culture
      experiments with the rat chondrogenic cell line pColl(II)-EGFP-5. Pilot
      experiments showed a negative effect of Wnt-7a on the proliferation of three
      rodent chondrogenic cell lines, RCJ3.1(C5.18), CFK-2, and C1. To establish a
      reporter system for chondrogenic differentiation we then produced a stably
      transfected chondrogenic cell line based on RCJ3.1(C5.18) for further
      experiments, which expresses green fluorescence protein (EGFP) under the collagen
      type II promoter (pColl(II)-EGFP-5). This cell line permits convenient
      observation of green fluorescence as a marker for differentiation in life
      cultures. The colony size of this cell line in agarose suspension cultures was
      reduced to 20-40% of control, when exposed to Wnt-1, 3a, 4, 7a, and 7b for 14
      days. Similarly, reporter gene expression and the synthesis of cartilage-specific
      proteoglycans were inhibited by this group of Wnts. In contrast, pColl(II)-EGFP-5
      cells exposed to Wnt-5a and Wnt-11 reached 140% of control, and reporter gene
      expression and proteoglycan synthesis were stimulated. The effects of Wnt-7a and
      Wnt-5a were additive in pColl(II)-EGFP-5 cells and some but not all Wnt effects
      were antagonized by the inhibition of proteoglycan sulfation with chlorate, by
      sFRP-2, which may modulate Wnt receptor binding, or by inhibitors of protein
      kinase C. These results suggest two functional Wnt subclasses that differentially
      regulate proliferation and chondrogenic differentiation in vitro which may have
      implications for cartilage differentiation in vivo. Since some, but not all Wnt
      effects were sensitive to inhibitors of proteoglycan synthesis or protein kinase
      C, multiple modes of signal transduction may be involved.

PMID- 11336785
TI  - Mannose 6-phosphate-independent endocytosis of beta-glucuronidase by human
      fibroblasts. I. Evidence for the existence of a membrane-binding activity.
AB  - Prior work has shown that endocytosis of bovine beta-glucuronidase by human
      fibroblasts can be mediated by the existence of a Man6P-independent receptor for
      the recapture and targeting to lysosomes. In this study, we have isolated a
      peptide (IIIb2) from pronase digested bovine beta-glucuronidase that behaved as
      competitive inhibitor of the endocytosis of bovine beta-glucuronidase by human
      fibroblasts. This peptide contained a Ser-X-Ser sequence, where X is probably a
      posttranslational modified Trp. Antibodies raised against this peptide impaired
      the endocytosis of the bovine but not the human beta-glucuronidase, implying that
      the new recognition marker for the endocytosis of acid hydrolases might reside in
      a single discrete stretch of amino acid sequence. On the other hand, bovine beta
      glucuronidase has been shown to bind specifically to receptors of human
      fibroblast membranes. The binding was saturable, divalent cation-dependent and
      was competitively inhibited by the IIIb2 peptide, but not by mannose 6-phosphate.
      Results presented suggested an interplay between manganese concentrations,
      temperature and pH on the dissociation of the beta-glucuronidase-receptor
      complexes. All together, these data reinforce the presence of two endocytic
      systems for the recapture and targeting of beta-glucuronidase in human
      fibroblasts.

PMID- 11336786
TI  - Mannose 6-phosphate-independent endocytosis of beta-glucuronidase. II.
      Purification of a cation-dependent receptor from bovine liver.
AB  - A new binding protein, which recognizes a specific peptide sequence from pronase
      digested bovine beta-glucuronidase, has been isolated from bovine liver
      membranes. Prior work has shown that this peptide (IIIb2) contains a Ser-X-Ser
      sequence, where X might be a posttranslational modified Trp. This receptor was
      detergent-extracted from total bovine liver membranes and purified by affinity
      chromatography on a bovine beta-glucuronidase-Sepharose and a IIIb2 peptide
      Sepharose column. Binding of bovine beta-glucuronidase to the isolated receptor
      requires divalent cations, and their presence was necessary to maintain the
      receptor-ligand complex. Only the peptide sequence containing the fraction IIIb2
      was able to impair the binding of the bovine enzyme to the receptor, no other
      peptide from bovine beta-glucuronidase had an effect on binding. When analyzed by
      SDS-PAGE under reducing conditions, two bands were observed, a major band of 78
      kDa and a faint band of 72 kDa. Rabbit antibodies against this binding protein
      revealed the presence of the 78 kDa protein in membranes from bovine liver, human
      and bovine fibroblasts. These antibodies impaired human fibroblasts endocytosis
      of the bovine but not of the human beta-glucuronidase, which is taken up by a 300
      kDa receptor that recognizes phosphomannosyl moieties in the enzyme.

PMID- 11336788
TI  - Three kinds of currents in the canine betaine-GABA transporter BGT-1 expressed in
      Xenopus laevis oocytes.
AB  - The cloned canine betaine-GABA cotransporter BGT-1 has been heterologously
      expressed in Xenopus laevis oocytes in order to characterize its
      electrophysiological properties. Voltage-clamp experiments on transfected oocytes
      reveal the presence of three types of membrane current which are absent in non
      injected oocytes: (i) an organic substrate-independent current (uncoupled
      current); (ii) a transport-associated current, seen upon addition of betaine or
      GABA; (iii) presteady-state currents induced by voltage changes. The three kinds
      of current are analogous to those reported in structurally similar
      cotransporters. The transport-associated current is strictly dependent on the
      presence of Na(+). The good correlation between the amount of charge underlying
      the presteady-state currents and the transport-associated current indicates that
      both processes are due to the activity of the transporter.

PMID- 11336787
TI  - Molecular properties of apelin: tissue distribution and receptor binding.
AB  - We analyzed the tissue distribution of apelin mRNA in rats by a quantitative
      reverse transcription-polymerase chain reaction and that of immunoreactive apelin
      (ir-apelin) by an enzyme immunoassay (EIA) using a monoclonal antibody. The
      expression levels of apelin mRNA and ir-apelin seemed to be consistent among
      tissues: they were highly expressed in the lung and mammary gland. By the
      combination of gel filtration and EIA, we found that the molecular forms of
      apelin differ among respective tissues: apelin molecules with sizes close to
      apelin-36 (long forms) were major components in the lung, testis, and uterus, but
      both long and short (whose sizes were close to [<Glu(65)]apelin-13) forms were
      detected in the mammary gland. In Scatchard analyses, the radioiodinated apelin
      36 analogue bound to the receptor, APJ, with high affinity. In competitive
      binding assays, apelin-36 and apelin-19 far more efficiently inhibited the
      binding of the labeled apelin-36 analogue with APJ than [<Glu(65)]apelin-13. In
      analyses for the dissociation of apelin from APJ, unlabeled apelin-36 replaced
      more rapidly the labeled apelin-36 analogue bound with APJ than [<Glu(65)]apelin
      13. Our results demonstrate that the long and short forms of apelin differently
      interact with APJ.

PMID- 11336789
TI  - Role of guanine nucleotides in the regulation of the Ras/cAMP pathway in
      Saccharomyces cerevisiae.
AB  - The CDC25 gene product is a guanine nucleotide exchange factor for Ras proteins
      in yeast. Recently it has been suggested that the intracellular levels of guanine
      nucleotides may influence the exchange reaction. To test this hypothesis we
      measured the levels of nucleotides in yeast cells under different growth
      conditions and the relative amount of Ras2-GTP. The intracellular GTP/GDP ratio
      was found to be very sensitive to growth conditions: the ratio is high, close to
      that of ATP/ADP during exponential growth, but it decreases rapidly before the
      beginning of stationary phase, and it drops further under starvation conditions.
      The addition of glucose to glucose-starved cells causes a fast increase of the
      GTP/GDP ratio. The relative amount of Ras2-GTP changes in a parallel way
      suggesting that there is a correlation with the cytosolic GTP/GDP ratio. In
      addition 'in vitro' mixed-nucleotide exchange experiments done on purified Ras2
      protein demonstrated that the GTP and GDP concentrations influence the extent of
      Ras2-GTP loading giving further support to their possible regulatory role.

PMID- 11336790
TI  - Biphasic cytotoxic mechanism of extracellular ATP on U-937 human histiocytic
      leukemia cells: involvement of adenosine generation.
AB  - Since extracellular ATP can exhibit cytotoxic activity in vivo and in vitro, its
      application has been proposed as an alternative anticancer therapy. In this study
      we investigated the mechanisms of ATP-induced cytotoxicity in a human leukemic
      cell line (U-937). ATP added as a single dose exceeding 50 microM was cytostatic
      or even cytotoxic for U-937 cells. Interestingly, growth inhibition by ATP (50
      3500 microM) showed a biphasic dose response. Up to 800 microM, ATP was cytotoxic
      in a dose-dependent manner (EC(50) 90 microM). In a range between 800 and 2500
      microM, cell count was markedly higher despite the higher ATP concentrations. The
      cytotoxic effect of ATP could be antagonized by addition of uridine as a
      pyrimidine source and, alternatively, by addition of the nucleoside transmembrane
      inhibitor dipyridamole. The apoptosis-inducing adenosine A(3) receptor was not
      involved in measurable quantities, since (1) adenosine did not lead to an
      elevation of intracellular calcium levels, and (2) an unselective A(1-3)
      antagonist (ULS-II-80) could not abrogate the cytotoxic effect. Experiments
      monitoring extracellular nucleotide metabolism confirmed the assumption that the
      long-term production and continuous uptake of adenosine, which is extracellularly
      generated by degradation of ATP, led to an intracellular nucleotide imbalance
      with pyrimidine starvation. The biphasic dose response to higher ATP
      concentrations could be explained by the rapid degradation of lower ATP
      concentrations (300 microM) to adenosine by serum-derived enzymes, whereas higher
      concentrations (900 microM) only produced small amounts of adenosine due to
      forward inhibition of AMP hydrolysis by prolonged high ADP levels. FACS analysis
      revealed that at lower adenosine concentrations (300 microM) a reversible G(1)
      phase arrest of the cell cycle was induced, whereas higher concentrations (1000
      microM) triggered apoptosis. Considering ATP as a potential cytostatic drug, our
      data have important implications concerning metabolic interactions of
      administered nucleotides.

PMID- 11336791
TI  - Analysis of inhibition by H89 of UCP1 gene expression and thermogenesis indicates
      protein kinase A mediation of beta(3)-adrenergic signalling rather than beta(3)
      adrenoceptor antagonism by H89.
AB  - Although it has generally been assumed that protein kinase A (PKA) is essential
      for brown adipose tissue function, this has not as yet been clearly demonstrated.
      H89, an inhibitor of PKA, was used here to inhibit PKA activity. In cell
      extracts, it was confirmed that norepinephrine stimulated PKA activity, which was
      abolished by H89 treatment. In isolated brown adipocytes, H89 inhibited
      adrenergically induced thermogenesis (with an IC(50) of approx. 40 microM), and
      in cultured cells, adrenergically stimulated expression of the uncoupling protein
      1 (UCP1) gene was abolished by H89 (full inhibition with 50 microM). However, H89
      has been reported to be an adrenergic antagonist on beta(1)/beta(2)-adrenoceptors
      (AR). Although adrenergic stimulation of thermogenesis and UCP1 gene expression
      are mediated via beta(3)-ARs, it was deemed necessary to investigate whether H89
      also had antagonistic potency on beta(3)-ARs. It was found that EC(50) values for
      beta(3)-AR-selective stimulation of cAMP production (with BRL-37344) in brown
      adipose tissue membrane fractions and in intact cells were not affected by H89.
      Similarly, the EC(50) of adrenergically stimulated oxygen consumption was not
      affected by H89. As H89 also abolished forskolin-induced UCP1 gene expression,
      and potentiated selective beta(3)-AR-induced cAMP production, H89 must be active
      downstream of cAMP. Thus, no antagonism of H89 on beta(3)-ARs could be detected.
      We conclude that H89 can be used as a pharmacological tool for elucidation of the
      involvement of PKA in cellular signalling processes regulated via beta(3)-ARs,
      and that the results are concordant with adrenergic stimulation of thermogenesis
      and UCP1 gene expression in brown adipocytes being mediated via a PKA-dependent
      pathway.

PMID- 11336792
TI  - Mitogen-activated protein kinase pathway is involved in alpha6 integrin gene
      expression in androgen-independent prostate cancer cells: role of proximal Sp1
      consensus sequence.
AB  - Metastatic diseases of prostate cancer reveal high expression of alpha6 integrin
      and the activation of mitogen-activated protein kinases (MAP kinase). Therefore,
      the present study was conducted to examine whether MAP kinase pathway is involved
      in the alpha6 integrin gene expression in androgen-independent prostate cancer
      cell lines. alpha6 integrin mRNA expression, the alpha6 integrin promoter-induced
      luciferase activities and MAP kinase enzyme activities in androgen-independent
      LNCaP and PC-3 cell lines were higher than those in androgen-dependent LNCaP.
      Deletion and mutation analysis showed that Sp1 consensus sequence at -48 to -43
      bp from the transcription start site was necessary for basal promoter activity.
      Binding of Sp1 to its consensus sequence in three cell lines was confirmed by
      electrophoretic mobility shift assays. Sp1 binding to its consensus sequence, as
      well as promoter activity and mRNA expression, were found to be inhibited by an
      inhibitor of MAP kinase kinase 1 and 2, U0126, in the androgen-independent cell
      lines. Our results indicate that the proximal Sp1 is necessary for basal promoter
      activity of the alpha6 integrin, suggesting that signal transduction from MAP
      kinases to activation of Sp1 might be involved in alpha6 integrin gene expression
      in androgen-independent prostate cancer cell lines.

PMID- 11336793
TI  - Fibroblast growth factors 1 and 2 differently activate MAP kinase in Xenopus
      oocytes expressing fibroblast growth factor receptors 1 and 4.
AB  - The mitogen-activated protein kinase (MAP kinase) signalling cascade activated by
      fibroblast growth factors (FGF1 and FGF2) was analysed in a model system, Xenopus
      oocytes, expressing fibroblast growth factor receptors (FGFR1 and FGFR4).
      Stimulation of FGFR1 by FGF1 or FGF2 and FGFR4 by FGF1 induced a sustained
      phosphorylation of extracellular signal-regulated protein kinase 2 (ERK2) and
      meiosis reinitiation. In contrast, FGFR4 stimulation by FGF2 induced an early
      transient activation of ERK2 and no meiosis reinitiation. FGFR4 transduction
      cascades were differently activated by FGF1 and FGF2. Early phosphorylation of
      ERK2 was blocked by the dominant negative form of growth factor-bound protein 2
      (Grb2) and Ras, for FGF1-FGFR4 and FGF2-FGFR4. The phosphatidylinositol 3-kinase
      (PI3 kinase) inhibitors wortmannin and LY294002 only prevented the early ERK2
      phosphorylation triggered by FGF2-FGFR4 but not by FGF1-FGFR4. ERK2
      phosphorylation triggered by FGFR4 depended on the Grb2/Ras pathway and also
      involved PI3 kinase in a time-dependent manner.

PMID- 11336794
TI  - Daunorubicin attenuates tumor necrosis factor-alpha-induced biosynthesis of
      plasminogen activator inhibitor-1 in human umbilical vein endothelial cells.
AB  - The anthracycline antibiotic daunorubicin is reported to induce apoptosis in
      cells by triggering ceramide generation through de novo synthesis or
      sphingomyelin hydrolysis. Treatment of human umbilical vein endothelial cells
      (HUVEC) with daunorubicin markedly decreased the mRNA expression and protein
      release of plasminogen activator inhibitor-1 (PAI-1). This cellular event was
      accompanied by a significant increase in the total ceramide content in HUVEC. On
      the other hand, tumor necrosis factor (TNF)-alpha treatment of HUVEC led to an
      increase in both PAI-1 mRNA expression and protein release, and an enhancement of
      total ceramide content was also observed. The stimulating effect of TNF-alpha on
      PAI-1 synthesis was attenuated by the pretreatment of HUVEC with daunorubicin.
      Interestingly, the daunorubicin-induced increase in ceramide content was blocked
      by addition of the potent ceramide synthase inhibitor fumonisin B(1), while the
      TNF-alpha-induced ceramide increase was not affected by this drug. Fumonisin B(1)
      treatment restored the daunorubicin-induced decrease in PAI-1 release to
      approximately 70% of the control, but did not affect the TNF-alpha-induced
      increase in PAI-1 release. Thus, these data imply the possibility that the
      subcellular topology of ceramide production determines its lipid mediator
      function in the regulation of PAI-1 synthesis in HUVEC, because both TNF-alpha
      and daunorubicin could increase the ceramide levels.

PMID- 11336795
TI  - The effects of wild-type and mutant HFE expression upon cellular iron uptake in
      transfected human embryonic kidney cells.
AB  - In order to measure the effects of HFE (haemochromatosis) upon iron uptake,
      stable expression of wild-type and C282Y, H63D and S65C mutant HFE cDNA was
      established in HEK 293 cells. Control cells were transfected with empty vector.
      Expression of HFE mRNA and protein was detected in the cell lines transfected
      with HFE cDNA, but not in the control cell line. The ferritin concentration in
      wild-type cells cultured in 40 microM ferric ammonium citrate was 69% of that in
      control cells and 81% of that in C282Y cells. The ferritin concentration in H63D
      cells was intermediate between wild-type and C282Y and the ferritin concentration
      in S65C cells was similar to wild-type cells. Uptake of transferrin-iron in wild
      type, C282Y and control cells was measured over 45 min. The Hill coefficients for
      transferrin-iron uptake were similar. The V(max) for transferrin-iron uptake in
      wild-type cells was 59.5% of control cells and 69.5% of C282Y cells. Estimates of
      K(m) were 232 nM for wild-type cells, 338 nM for C282Y cells and 570 nM for
      controls. Transferrin receptor levels were lowered, but not significantly, in the
      HFE transfected cells. The results show that HFE reduces transferrin-iron uptake,
      probably as an uncompetitive inhibitor.

PMID- 11336796
TI  - Receptor-independent effects of natural cannabinoids in rat peritoneal mast cells
      in vitro.
AB  - Cannabinoids can activate CB(1) and CB(2) receptors. Since a CB(2) mRNA has been
      described in rat peritoneal mast cells (RPMC), we investigated a series of
      cannabinoids and derivatives for their capacity to stimulate RPMC. Effects of
      natural cannabinoids Delta(9)-tetrahydrocannabinol (Delta(9)-THC), Delta(8)-THC,
      endocannabinoids (anandamide, palmitoylethanolamide) and related compounds (N
      decanoyl-, N-lauroyl-, N-myristoyl-, N-stearoyl- and N-oleoyl-ethanolamines; N
      palmitoyl derivatives (-butylamine, -cyclohexylamine, -isopropylamine); and N
      palmitoyl, O-palmitoylethanolamine), and synthetic cannabinoids including WIN
      55,212-2, SR141716A and SR144528 were assessed for their capacity to induce
      histamine release or prime RPMC stimulated by compound 48/80. Only Delta(9)-THC
      and Delta(8)-THC could induce non-lytic, energy- and concentration-dependent
      histamine releases from RPMC (respective EC(50) values: 23.5+/-1.2; 53.4+/-20.6
      microM, and maxima: 71.2+/-5.5; 55.7+/-2.7% of the total RPMC histamine content).
      These were not blocked by CB(1) (SR141716A) or CB(2) (SR144528) antagonists, but
      reduced by pertussis toxin (100 ng/ml). Endocannabinoids and analogues did
      neither induce histamine secretion, nor prime secretion induced by compound 48/80
      (0.2 microg/ml). Delta(9)-THC and Delta(8)-THC induced in vitro histamine
      secretion from RPMC through CB receptor-independent interactions, partly
      involving G(i/o) protein activation.

PMID- 11336797
TI  - LIM domain protein Trip6 has a conserved nuclear export signal, nuclear targeting
      sequences, and multiple transactivation domains.
AB  - Trip6 is a member of a subfamily of LIM domain proteins, including also zyxin,
      LPP, Ajuba, and Hic-5, which localize primarily to focal adhesion plaques.
      However, in this report, we demonstrate that Trip6 is largely in the nucleus in
      cells treated with leptomycin B, suggesting that Trip6 shuttles between nuclear
      and cytoplasmic compartments and that nuclear export of Trip6 is dependent on
      Crm1. Consistent with this finding, we have identified a nuclear export signal
      (NES) in Trip6, and mutation of this NES also results in sequestration of Trip6
      in the nucleus. Addition of the Trip6 NES to the nuclear v-Rel oncoprotein
      redirects v-Rel to the cytoplasm. Trip6 also has at least two sequences that can
      direct cytoplasmic beta-galactosidase to the nucleus. Using GAL4 fusion proteins
      and reporter gene assays, we demonstrate that Trip6 has multiple transactivation
      domains, including one that appears to overlap with sequences of the NES. In
      vitro- or in vivo-synthesized Trip6, however, does not bind to DNA-cellulose.
      Taken together, these results are consistent with Trip6, and other members of
      this LIM protein family, having a role in relaying signals between focal adhesion
      plaques and the nucleus.

PMID- 11336798
TI  - Release of pro- and anti-angiogenic factors by human cardiac fibroblasts: effects
      on DNA synthesis and protection under hypoxia in human endothelial cells.
AB  - Myocardium consists of diverse cell types suggesting a role for cell-cell
      interaction in maintaining the structural and functional integrity of the heart.
      Cardiac fibroblasts are the source of extracellular matrix, growth factors and
      cytokines in the heart and their interactions with cardiac myocytes are
      recognized. Their effects on biological responses of endothelial cells, however,
      are vastly unexplored. Proliferation of endothelial cells is an essential stage
      of angiogenesis and contributes to development of coronary collaterals. This
      study was designed to evaluate the effect of soluble factors produced by cardiac
      fibroblasts on endothelial cell proliferation. Human cardiac fibroblast
      conditioned medium (CF-CM) caused a significant increase (47%, P < 0.0001) in DNA
      synthesis in human umbilical vein endothelial cells (HUVEC), as determined by
      [(3)H]thymidine incorporation. This effect was dependent on de novo protein
      synthesis and activation of MAP kinases. Consistently, CF-CM induced the
      expression and activation of ERK2 in HUVEC. The CF-CM from which heparin-binding
      proteins were removed, had a significantly enhanced stimulatory effect on DNA
      synthesis in HUVEC compared to that of 'whole CF-CM'. Western analysis showed the
      presence of VEGF, bFGF, PDGF, TGF-beta(1), fibronectin and thrombospondin-1 in
      whole CF-CM. The individual immunodepletion of each factor from whole CF-CM
      showed that all were necessary for full activity of CF-CM. CF-CM caused a
      significant reversal of hypoxia-induced inhibition of DNA synthesis and enhanced
      expression of survival-associated protein, Bcl(2), in HUVEC. Together, these data
      show that cardiac fibroblasts release inhibitory and stimulatory factors, the net
      effect of which is an enhancement of DNA synthesis in endothelial cells. These
      results point to the role that cardiac fibroblasts may play in angiogenesis in
      the heart.

PMID- 11336799
TI  - Hyaluronan reduces migration and proliferation in CHO cells.
AB  - Expression of the hyaluronan synthase gene in hyaluronan-deficient CHO cells
      changed the cell morphology from a spindle shape to a flattened epithelial-type
      form. Hyaluronan producing CHO cells showed reduced initial cell adhesion,
      migration, proliferation and density at contact inhibition, but no difference in
      random migration determined by the Boyden chamber assay. Addition of hyaluronan
      to the medium of CHO cells reduced migration, proliferation and initial cell
      adhesion. In contrast, coating the plastic dish with hyaluronan enhanced initial
      cell adhesion. These results are discussed in the context of the perplexing
      properties of hyaluronan on cellular functions.

PMID- 11336800
TI  - Zinc(II)-mediated enhancement of the agonist activity of histidine-substituted
      parathyroid hormone(1-14) analogues.
AB  - Previous studies on parathyroid hormone (PTH)(1-14) revealed that residues (1-9)
      played a dominant role in stimulating PTH-1 receptor-mediated increases in cAMP
      formation. In the present study, we examined the effects of installing a metal
      binding motif in the (10-14) region of rat PTH(1-14) on the peptide's agonist
      activity. We found that substitution of histidine for the native asparagine at
      position 10 of PTH(1-14) provided a peptide that was approx. 8-fold more potent
      as an agonist in the presence of divalent zinc salts than it was in the absence
      of the metal. This enhancement in potency was dependent on the native histidine
      at position 14, the concentration of Zn(II) utilized, and did not occur with
      other divalent metal ions. The zinc-activated [His(10)]-PTH(1-14) peptide was
      blocked by a classical PTH-1 receptor antagonist, PTHrP(7-36), and did not
      activate the PTH-2 receptor. The zinc-mediated enhancing effect did not require
      the large N-terminal extracellular domain of the PTH-1 receptor. Although we were
      able to demonstrate that [His(10)]-PTH(1-14) binds Zn(II) using (1)H-NMR, our
      spectroscopic studies (circular dichroism and nuclear magnetic resonance) were
      not consistent with the notion that zinc enhanced the activity of [His(10)]-PTH(1
      14) simply by inducing a helical structure in the 10-14 region. Rather, the data
      suggest that the enhancement in cAMP potency arises from the formation of a
      ternary complex between [His(10)]-PTH(1-14), a zinc atom, and the extracellular
      loop/transmembrane domain region of the PTH-1 receptor.

PMID- 11336801
TI  - Ku protein in human T and B lymphocytes: full length functional form and signs of
      degradation.
AB  - DNA-dependent protein kinase (DNA-PK) has been shown to take part in cell cycle
      regulatory signal transduction and in the repair of X-ray-induced DNA double
      strand breaks. Functional DNA-PK is furthermore needed for the generation of
      antigen specificity during lymphocyte maturation. The Ku86 subunit of DNA-PK has
      been reported to exist in human B lymphocytes in a truncated form capable of
      binding to broken DNA but lacking the ability to activate the kinase function of
      DNA-PK. In the present work the Ku70 and Ku86 dimer proteins in T and B
      lymphocytes from human blood donors were analysed by immunoblotting and were
      observed apparently to be of full length. Also, nuclear protein extracted from B
      and non-B lymphocytes displayed DNA-dependent kinase activity. However, a minor
      fraction of Ku86 in lymphocytes was observed to be truncated with a molecular
      mass of approx. 70 kDa.

PMID- 11336802
TI  - Reduction of phospholemman expression decreases osmosensitive taurine efflux in
      astrocytes.
AB  - The role of phospholemman (PLM) in taurine and Cl(-) efflux elicited by 30%
      hyposmotic solution was studied in cultured cerebellar astrocytes with reduced
      PLM expression by antisense oligonucleotide (AO) treatment. PLM, a substrate for
      protein kinases (PK) C and A, is a protein that increases an anion current in
      Xenopus oocytes and forms taurine-selective channels in lipid bilayers. Taurine
      contributes as an osmolyte to regulatory volume decrease (RVD) and is highly
      permeable through PLM channels in bilayers. Two antisense oligonucleotides (AO1
      and AO2) effectively decreased the expression of the PLM protein by 40% and 30%,
      respectively, and markedly reduced [(3)H]taurine efflux by 67% and 62%. AO
      treatment also decreased the osmosensitive release of Cl(-), followed as (125)I.
      The inhibition of Cl(-) efflux (23% for AO1 and 13% for AO2) was notably lower
      than for [(3)H]taurine. The contribution of PKC and PKA in the function of PLM
      was also evaluated in astrocytes. Pharmacological activation or inhibition of PKC
      and PKA revealed that the osmosensitive taurine efflux is essentially PKC
      independent while (125)I efflux is reduced by the PKC blockers H-7 (21%) and
      Go6983 (41%). The PKA activator forskolin and dbcAMP increased taurine efflux by
      66-70% and (125)I efflux by 21-45%. Norepinephrine increased the osmosensitive
      taurine efflux at about the same extent as dbcAMP and forskolin, and this was
      reduced by PKA blockers. These results suggest that PLM plays a role in RVD in
      astrocytes by predominantly influencing taurine fluxes, which are modulated by
      PKA but not PKC.

PMID- 11336803
TI  - Protein oxidation and proteolysis in RAW264.7 macrophages: effects of PMA
      activation.
AB  - Macrophages are stimulable cells able to increase the production of reactive
      oxygen and nitrogen species dramatically for a short period of time. Free
      radicals and other oxidants are able to oxidize the intracellular protein pool.
      These oxidized proteins are selectively recognized and degraded by the
      intracellular proteasomal system. We used the mouse macrophage-like cell line
      RAW264.7 to test whether macrophagial cells are able to increase their protein
      turnover after oxidative stress and whether this is accompanied by an increased
      protein oxidation. Macrophagial cells are particularly susceptible to bolus
      additions of hydrogen peroxide and peroxynitrite. In further experiments we
      activated RAW264.7 cells with PMA to test whether the production of endogenous
      oxidants has analogous effects. A clear dependence of the protein turnover and
      protein oxidation on the oxidative burst could be measured. In further
      experiments the role of the proteasomal system in the selective removal of
      oxidized proteins could be revealed exploring the proteasome specific inhibitor
      lactacystin. Therefore, although oxidants are able to attack the intracellular
      protein pool in macrophages, these cells are able to remove oxidized proteins
      selectively and protect the intracellular protein pool from oxidation.

PMID- 11336804
TI  - Hormonal regulation of phospholipase D activity in Ca(2+) transporting cells of
      rabbit connecting tubule and cortical collecting duct.
AB  - Phospholipase D (PLD) is distributed widely in mammalian tissues where it is
      believed to play an important role in the regulation of cell functions and cell
      fate by a variety of extracellular signals. In this study, we used primary
      cultures of rabbit connecting tubule (CNT) and cortical collecting duct (CCD)
      cells, grown to confluence on a permeable support, to investigate the possible
      involvement of PLD in the mechanism of action of hormones that regulate Ca(2+)
      reabsorption. RT-PCR revealed the presence of transcripts of PLD1b and PLD2, but
      not PLD1a, in these cultures. Moreover, the expression of substantial amounts of
      PLD1 protein was demonstrated by Western blotting. To measure PLD activity, cells
      were labelled with [(3)H]myristic acid after which the PLD-catalysed formation of
      radiolabelled phosphatidylethanol ([(3)H]PtdEth) was measured in the presence of
      1% (v/v) ethanol. Deamino-Cys,D-Arg(8)-vasopressin (dDAVP) and N(6)
      cyclopentyladenosine (CPA), two potent stimulators of Ca(2+) transport across
      these monolayers, stimulated PLD activity as was indicated by a marked increase
      in [(3)H]PtdEth. Similarly, ATP, a potent inhibitor of dDAVP- and CPA-stimulated
      Ca(2+) transport, increased the formation of [(3)H]PtdEth. PLD activity was
      furthermore increased by 8Br-cAMP and following acute (30 min) stimulation of
      protein kinase C (PKC) with a phorbol ester (PMA). Chronic PMA treatment (120 h)
      to downregulate phorbol ester-sensitive PKC isoforms did not affect PLD
      activation by dDAVP, CPA and 8Br-cAMP, while markedly decreasing the effect of
      ATP and abolishing the effect of PMA. The PKC inhibitor chelerythrine
      significantly reduced PLD activation by dDAVP, CPA and 8Br-cAMP, without changing
      the effect of ATP. The inhibitor only partially reduced the effect of PMA. This
      study shows that Ca(2+) transporting cells of CNT and CCD contain a regulated PLD
      activity. The physiological relevance of this activity, which is not involved in
      Ca(2+) reabsorption, remains to be established.

PMID- 11336805
TI  - Molecular analysis of a novel Drosophila diacylglycerol kinase, DGKepsilon.
AB  - Diacylglycerol kinase plays a central role in the metabolism of diacylglycerol by
      converting diacylglycerol into phosphatidic acid thus initiating resynthesis of
      phosphatidylinositols. Diacylglycerol is a known second messenger reversibly
      activating protein kinase C. In addition, diacylglycerol is a potential precursor
      for polyunsaturated fatty acids. We describe the identification and molecular
      analysis of a novel type III Drosophila diacylglycerol kinase isoform,
      DGKepsilon. Drosophila DGKepsilon is mapped to the cytological position 49C1-3.
      DGKepsilon mRNA is 1.9 kb in length and is broadly distributed throughout
      development in different cells, primordia and organs, including testes. In
      embryogenesis, the transcripts are enriched in the cells, which are in S-phase or
      undergoing endoreplication. Comparison of the Drosophila DGKepsilon with the
      human homologue revealed that the first zinc finger-like motif is specific for
      the type III isoform. Although the testis-specific diacylglycerol kinase activity
      is dependent upon the dose of DGKepsilon gene, the deletion of DGKepsilon does
      not modulate the total cellular diacylglycerol level. In spite of a proposed key
      role of diacylglycerol kinase in termination of the diacylglycerol signal,
      overexpression of a DGKepsilon transgene in flies under the control of a yeast
      upstream activating sequence promoter does not disrupt normal development in
      Drosophila.

PMID- 11336806
TI  - Transfer of quinolizidine alkaloids from hosts to hemiparasites in two Castilleja
      Lupinus associations: analysis of floral and vegetative tissues.
AB  - Many hemiparasites, including several members of the Castilleja genus
      (Scrophulariaceae), obtain secondary compounds from their host plants. Both
      Castilleja miniata in subalpine Colorado and C. indivisa in central Texas have
      reduced herbivory when obtaining alkaloids from the hosts Lupinus argenteus and
      L. texensis (Fabaceae), respectively. However, pollinators were not deterred from
      visiting Castilleja parasitizing alkaloid-containing hosts. To determine if
      alkaloids are present in all tissues of plants parasitizing lupins, we analyzed
      floral tissue as well as leaves of both Castilleja species. Leaves, bracts,
      calices, corollas, gynoecium and nectar of both Castilleja species were examined
      for quinolizidine alkaloid presence using a Dragendorff reagent, and alkaloids
      were identified in vegetative tissue and nectar by capillary GLC and GLC-MS.
      Lupanine and alpha-isolupanine were the principal alkaloids in C. indivisa
      parasitizing L. texensis, while principal alkaloids of C. miniata parasitizing L.
      argenteus were 5,6-iso-dehydrolupanine, alpha-isolupanine, thermopsine, and 17
      oxolupanine. Except for 17-oxolupanine, which was probably synthesized by
      biotransformation in the parasite, all other alkaloids correspond to those
      present in the host plants. Alkaloids were present in the leaves of both
      Castilleja species, and in the bracts, calices and gynoecium of some plants, but
      never in the corollas. Alkaloids from L. texensis and L. argenteus were not
      detected in nectar of either Castilleja species. The presence of alkaloids in
      leaves and outer floral tissue of both Castilleja species, but not nectar, may
      explain why alkaloid uptake and storage affected herbivores but not pollinators.

PMID- 11336807
TI  - Estimation and management of genetic diversity in small populations of plains
      zebra (Equus quagga) in KwaZulu-Natal, South Africa.
AB  - Plains zebras (Equus quagga antiquorum) occur in few large, but many small,
      isolated populations in KwaZulu-Natal. Problems identified in small populations
      include reduced striping patterns on hind quarters, smaller size, elevated
      mortality rates and high number of still-births. Inbreeding may be implicated.
      Population viability analysis (PVA) was conducted with a computer model (VORTEX),
      and DNA and allozyme analyses were conducted to test the findings of the model.
      Using standard methods, DNA (PCR-RAPD) and allozyme diversity was assessed in
      blood samples from 72 plains zebra from four KwaZulu-Natal Nature Conservation
      Services (KZN-NCS) protected areas: Umfolozi Game Reserve (UGR), Albert Falls
      (AFNR), Vernon Crookes (VCNR) and Harold Johnson (HJNR) Nature Reserves.
      Populations of the latter three, small-sized (9-110 individuals) populations were
      seeded from the same source population (UGR: current population of 2000) during
      the past 25 years. Information from PCR-RAPD and allozyme analyses were compared
      with each other as well as to that predicted by population genetic modelling
      (using VORTEX). Allozyme heterozygosities were consistently high in all
      populations (12.1-12.9%), with no observable losses associated with reduced
      population size. On the other hand, percentage loss of polymorphism (20-39%)
      calculated from the PCR-RAPD study appeared to be positively correlated with the
      loss of heterozygosity predicted by population viability analysis (PVA), and
      negatively correlated with population size. On the basis of the above results, a
      policy of translocation was advocated for small, intensely managed populations of
      zebras, whereby a harem should be translocated every five years for a population
      size of nine (HJNR), while for a population size of 110 (VCNR) translocations
      should take place every 15 years if heterozygosity is to be maintained at more
      than 90% within each population over 100 years.

PMID- 11336808
TI  - Molecular phylogeny of Myomys/Stenocephalemys complex and its relationships with
      related African genera.
AB  - Partial 16S rRNA mitochondrial gene sequences were used to infer the phylogenetic
      relationships among Stenocephalemys albocaudata, S. griseicauda and Myomys
      albipes, three closely related Ethiopian endemic murines and a selection of
      related species (Myomys daltoni, Praomys delectorum, Mastomys natalensis,
      Hylomyscus kaimosae, and Colomys goslingi) from other African regions. The
      obtained phylogeny confirms the close relationship between M. albipes and the two
      Stenocephalemys species, but it also suggests that both the genera Myomys and
      Stenocephalemys are paraphyletic, as M. albipes is closer to Stenocephalemys than
      to M. daltoni and S. griseicauda is more closely related to M. albipes than to S.
      albocaudata. These data, if confirmed, would argue that M. albipes should be
      renamed S. albipes. In conclusion, our study suggests that morphological
      similarity is not always a reliable measure for close genetic relationship in
      murines. Morphological similarity among species that evolved under similar
      ecological conditions can be the result of convergent evolution rather than a
      consequence of recent common ancestry.

PMID- 11336809
TI  - Determination of the anamorph of Cordyceps sinensis inferred from the analysis of
      the ribosomal DNA internal transcribed spacers and 5.8S rDNA.
AB  - The anamorph determination of Cordyceps sinensis remains problematic due to the
      lack of clear links between the sexual and conidial forms of the fungus. In this
      study, we applied molecular approaches to analyze the genetic variation of
      Cordyceps sinensis and its allies to identify the anamorph-teleomorph connection.
      The sequences of the internal transcribed spacers (ITS1 and ITS2) and 5.8S
      ribosomal RNA gene of Cordyceps sinensis (teleomorph) collected from Qingzang
      plateau (altitude over 4000m), Tibet and several related asexual conidial forms
      were determined. The sequence comparison showed that Cordyceps sinensis was most
      closely related to Hirsutella sinensis, and was clearly divergent from
      Paecilomyces sinensis, Stachybotrys sp. or Tolypocladium sp.; distance values,
      estimated according to Kimura two-parameter models between Cordyceps sinensis and
      Hirsutella sinensis, were extremely low (<0.02), whereas distance values between
      Cordyceps sinensis and Paecilomyces sinensis, Stachybotrys sp. and Tolypocladium
      sp. were 0.34, 0.21 and 0.25, respectively. Taken together, Hirsutella sinensis
      and Cordyceps sinensis are the different stages of the life cycle stages of the
      same organism. Hirsutella sinensis is therefore the anamorph of Cordyceps
      sinensis, rather than Paecilomyces sinensis or other species. The possible
      reasons as to why different taxa can be obtained when culturing Cordyceps
      sinensis are also discussed.

PMID- 11336810
TI  - Geographic variation in leaf essential oils and RAPDs of Juniperus polycarpos K.
      Koch in central Asia.
AB  - Variations in the composition of the leaf essential oils and DNA fingerprints
      (RAPDs) of Juniperus excelsa, J. polycarpos, J. seravschanica, and J. turcomanica
      were examined. Juniperus procera was also included in the analyses to aid in
      determining the specific status of J. polycarpos. Based on these analyses, J.
      polycarpos is recognized as a distinct species from J. excelsa. The common, multi
      seeded juniper of central Asia is J. polycarpos. Juniperus seravschanica and J.
      turcomanica are treated as part of the J. polycarpos complex but are not
      recognized as formal taxonomic groups at this time. The Balochistan, Pakistan
      juniper, usually called J. excelsa var. polycarpos or J. macropoda should be
      referred to as J. polycarpos in the future.

PMID- 11336811
TI  - A chemotaxonomic and morphological appraisal of Aloe series Purpurascentes, Aloe
      section Anguialoe and their hybrid, Aloe broomii.
AB  - Evidence is presented to suggest the hybrid origin of Aloe broomii, with the one
      putative parent belonging to Aloe series Purpurascentes and the other a member of
      Aloe series Anguialoe. A chemotaxonomic and morphological assessment is presented
      for both infrageneric groups and their hypothesised hybrid. Four of the species
      belonging to the series Purpurascentes display a characteristic leaf exudate
      profile containing the chemotaxonomic marker microstigmin. Aloe gariepensis and
      A. succotrina lack the diagnostic leaf exudate compounds. The distinct
      morphological apomorphies for Aloe section Anguialoe are supported on the
      chemical level reinforcing the monophyly of this group.

PMID- 11336812
TI  - Sesquiterpene lactones and other constituents of Disynaphia multicrenulata from
      Argentina.
AB  - Flowers and leaves of Disynaphia multicrenulata from Argentina afforded a large
      number of known germacradienolides and heliangolides, a new germacradienolide, a
      known melampolide, a new parthenolide derivative, one known and seven new
      cronquistiolides, a new 4Z-melampolide, three known and five new eudesmanolides,
      a new elemadienolide, a known grazielolide, an isoguaiagrazielolide, two
      diepoxygermacran-8,12-olides, three common kauranoic acids, pinoresinol,
      jaceosidin and the sesquiterpene oplopanone. Structures were elucidated by high
      field 1H NMR spectrometry. The relationship to the known chemistry of other
      members of the Disynaphiinae is discussed.

PMID- 11336813
TI  - Cyclopentanoids of Mathurina penduliflora.

PMID- 11336814
TI  - Flavonoids and other phenolics from leaves of two Marlierea species (Myrtaceae).

PMID- 11336815
TI  - Parthenolide from the aerial parts of Tanacetum larvatum.

PMID- 11336817
TI  - Abstracts of the 3rd Congress of the European Federation of Internal Medicine,
      Edinburgh, UK, 9-12 May 2001.

PMID- 11336816
TI  - Hypericum perforatum L. - chemotype without rutin from Italy.

PMID- 11336818
TI  - SecB, a molecular chaperone with two faces.
AB  - SecB is a molecular chaperone unique to the phylum Proteobacteria, which includes
      the majority of known Gram-negative bacteria of medical, industrial and
      agricultural significance. SecB is involved in the translocation of secretory
      proteins across the cytoplasmic membrane. The crystal structure of the
      Haemophilus influenzae SecB provides new insights into how SecB simultaneously
      recognizes its two ligands: unfolded preproteins and SecA, the ATPase subunit of
      the translocase. SecB uses its entire molecular surface for these two functions,
      but for preprotein release and its own membrane release, SecB relies on the
      catalytic activity of SecA. This defines SecB as a translocation-specific
      molecular chaperone.

PMID- 11336819
TI  - A marriage of bacteriology with cell biology results in twin arginines.
AB  - The Tat apparatus is a remarkable molecular machine required for the
      transmembrane translocation of folded proteins. Recent studies have identified
      jellyfish green fluorescent protein as an excellent reporter protein for the
      bacterial Tat pathway. Although the genetics of the Tat system are reasonably
      well-defined in Escherichia coli, the utilization of heterologous proteins as
      transport substrates promises to facilitate further mechanistic and structural
      characterization of this system.

PMID- 11336835
TI  - The meaning and impact of the human genome sequence for microbiology.
AB  - The characterization of life is immeasurably enhanced by determination of
      complete genome sequences. For organisms that engage in intimate interactions
      with others, the genome sequence from one participant, and associated tools,
      provide unique insight into its partner. We discuss how the human genome sequence
      will further our understanding of microbial pathogens and commensals, and vice
      versa. We also propose criteria for implicating a host gene in microbial
      pathogenesis, and urge consideration of a'second human genome project'.

PMID- 11336836
TI  - How and when are substrates selected for type III secretion?
AB  - Many Gram-negative bacteria use type III secretion systems to secrete virulence
      factors as well as the structural components of the flagellum. Some bacterial
      secretion systems use a secretion signal contained in the amino acid sequence of
      the secreted substrate. However, substrates of type III systems lack a single,
      defined secretion signal. There is evidence for the existence of three
      independent secretion signals - the 5' region of the mRNA, the amino terminus of
      the substrate and the ability of a secretion chaperone to bind the substrate
      before secretion - that direct substrates for secretion through the type III
      pathways. One or more of these signals might be used for a given substrate. A
      recent study of flagellar assembly presented evidence for a role of translation
      in the type III secretion mechanism. We present a unifying model for type III
      secretion that can be applied to flagellar assembly, needle assembly and the
      secretion of virulence factors. The potential role of translation in regulating
      the timing of substrate secretion is also discussed.

PMID- 11336837
TI  - Intimin and the host cell--is it bound to end in Tir(s)?
AB  - Intimate bacterial adhesion to the intestinal epithelium is a pathogenic
      mechanism shared by several human and animal enteric pathogens, including
      enteropathogenic and enterohaemorrhagic Escherichia coli. Two bacterial protein
      partners involved in this intimate association have been identified, intimin and
      Tir. Some key remaining questions include whether intimin specifically interacts
      with one or more host-cell-encoded molecules and whether these contacts are a
      prerequisite for the subsequent intimate intimin-Tir association. Recent data
      support the hypothesis that the formation of a stable intimin-Tir relationship is
      the consequence of intimin protein interactions involving both host and bacterial
      components.

PMID- 11336838
TI  - Model systems: Studying molecular recognition using bacterial n-hybrid systems.
AB  - Since the first description of the yeast two-hybrid system, related genetic
      assays for protein-protein interactions have become popular and powerful tools
      for structure-function analysis on the scale of individual proteins or whole
      proteomes. After a somewhat surprising lag, similar systems have recently been
      described for use in bacterial hosts. n-hybrid modifications of the original
      yeast system have been used to examine interactions with DNA, RNA and small
      molecules, and other modifications have improved throughput for genomic
      applications. Bacterial n-hybrid systems are being designed for a similar array
      of uses. Will the bacterial systems be as popular as the yeast n-hybrid systems?
      Only time will tell.

PMID- 11336839
TI  - The biofilm matrix--an immobilized but dynamic microbial environment.
AB  - The biofilm matrix is a dynamic environment in which the component microbial
      cells appear to reach homeostasis and are optimally organized to make use of all
      available nutrients. The major matrix components are microbial cells,
      polysaccharides and water, together with excreted cellular products. The matrix
      therefore shows great microheterogeneity, within which numerous microenvironments
      can exist. Although exopolysaccharides provide the matrix framework, a wide range
      of enzyme activities can be found within the biofilm, some of which will greatly
      affect structural integrity and stability.

PMID- 11336841
TI  - Interpreting cell wall 'virulence factors' of Mycobacterium tuberculosis.
AB  - The complex structure of the cell wall of Mycobacterium tuberculosis clearly
      contributes to the outcome of the dialogue between this pathogen and its host.
      The effects of mutations in cell wall components are likely to be quite complex,
      as individual components of the wall could have indirect effects that extend well
      beyond the physical integrity of the wall itself. Affected processes include the
      surface exposure or secretion of the many lipid, glycolipid and proteinaceous
      molecules that can interact directly with components of the host cell.

PMID- 11336840
TI  - Maturation of the [NiFe] hydrogenases.
AB  - The high degree of similarity that exists between all the [NiFe] hydrogenase
      operons and the near universality of hydrogen metabolism among microorganisms
      suggest that the microbial ability to metabolize hydrogen is of great importance
      and ancient origin. The large number of genes present in these operons, which are
      mostly involved in the maturation of the structural subunit, is indicative of the
      complexity of the hydrogenase molecular structure. Two main groups of maturation
      genes can be differentiated based on the resulting phenotypes when mutated: the
      'cis-genes', encoding narrow specificity proteins, are mainly located on the same
      transcription unit as the structural genes, and the 'trans-genes', encoding broad
      specificity proteins, are located on a different operon. The maturation of the
      large subunit starts with the formation of a complex with the chaperone HypC,
      which remains bound to the amino terminus throughout processing. The ligands CN
      and CO, which are derived from carbamoylphosphate, are then inserted via HypF and
      probably other accessory proteins. HypB is responsible for nickel atom delivery
      in a GTP-hydrolysis-dependent reaction. The last identified step in the large
      subunit maturation process is proteolytic cleavage at the carboxyl terminus. The
      possible roles of the other maturation proteins are also discussed.

PMID- 11336842
TI  - Management of acute-onset claudication.

PMID- 11336843
TI  - Development of oral heparin therapy for prophylaxis and treatment of deep venous
      thrombosis.
AB  - OBJECTIVE: To review the current research and published literature regarding the
      development of oral heparin therapy for the prophylaxis and treatment of deep
      venous thrombosis. BACKGROUND: Currently, the accepted practice of prophylaxis
      and/or treatment of acute deep venous thrombosis (DVT) is intravenous or
      subcutaneous (SQ) heparin followed by oral warfarin or SC low molecular weight
      heparin (LMWH) therapy followed by warfarin. Both of which are less than ideal.
      More recently, advances have been made towards an effective oral heparin
      preparation that would resolve many of the drawbacks to the current therapies.
      METHODS: A review of the current and relevant English literature identified via a
      search of the Medline database from January 1990 to present. RESULTS: Initial
      oral heparin therapy for DVT was unsuccessful due to presumed inadequate
      intestinal absorption as a result of heparin's molecular and structural
      characteristics. The development of oral heparin therapy, based on combining
      heparin with the carrier molecule Sodium N-(8[2-hydroxybenzoyl]amino) caprylate
      (SNAC) to enhance its intestinal absorption and bioavailability for the
      prophylaxis and treatment of DVT has been demonstrated to be effective in animal
      models. More recent efforts have been aimed at human trials. CONCLUSION: Recent
      advances in prophylaxis and treatment of DVT have stimulated great interest among
      researchers to develop an effective, convenient, and well tolerated oral therapy.
      An effective oral heparin therapy may represent an ideal method of prophylaxis
      and treatment of DVT.

PMID- 11336845
TI  - Vascular graft infections: an update.

PMID- 11336844
TI  - Long-term relative survival following surgery for abdominal aortic aneurysm: a
      review.
AB  - BACKGROUND: The literature reporting the long-term survival following surgery for
      abdominal aortic aneurysm (AAA) tends to be confusing. As a result, many
      clinicians looking after patients with AAA may be uncertain about the five-year
      survival of a given patient. This is in marked contrast to the situation for
      patients with malignant disease. With the current interest in population
      screening and endoluminal stenting for AAA, an understanding of long-term
      survival is increasingly important. METHODS: Thirty two publications in the
      English language over the last 20 years, containing data pertaining to five-year
      survival following routine elective surgery for AAA in unselected patients, were
      identified using Medline searches. RESULTS AND CONCLUSIONS: A range of important
      methodological differences were noted. The mean five-year crude survival was
      about 70% while the expected survival of a matched population was close to 80%.
      Survival was further reduced by about 10% in cases with significant coronary
      heart disease. Age alone is not a predictor of long-term relative survival with
      octogenarians who survive beyond 30 days surviving longer than an age-matched
      population.

PMID- 11336846
TI  - Initial results of ultrasound screening for aneurysm of the abdominal aorta in
      Western Australia: relevance for endoluminal treatment of aneurysm disease.
AB  - BACKGROUND: Increased life expectancy in men during the last thirty years is
      largely due to the decrease in mortality from cardiovascular disease in the age
      group 29--69 yr. This change has resulted in a change in the disease profile of
      the population with conditions such as aneurysm of the abdominal aorta (AAA)
      becoming more prevalent. The advent of endoluminal treatment for AAA has
      encouraged prophylactic intervention and fueled the argument to screen for the
      disease. The feasibility of inserting an endoluminal graft is dependent on the
      morphology and growth characteristics of the aneurysm. This study used data from
      a randomized controlled trial of ultrasound screening for AAA in men aged 65--83
      yr in Western Australia for the purpose of determining the norms of the living
      anatomy in the pressurized infrarenal aorta. AIMS: To examine (1) the diameters
      of the infra-renal aorta in aneurysmal and non-aneurysmal cases, (2) the
      implications for treatment modalities, with particular reference to endoluminal
      grafting, which is most dependent on normal and aneurysmal morphology, and (3)
      any evidence to support the notion that northern Europeans are predisposed to
      aneurysmal disease. METHODS: Using ultrasound, a randomized control trial was
      established in Western Australia to assess the value of a screening program in
      males aged 65--83 yr. The infra-renal aorta was defined as aneurysmal if the
      maximum diameter was 30 mm or more. Aortic diameter was modelled both as a
      continuous (in mm) and as a binary outcome variable, for those men who had an
      infra-renal diameter of 30 mm or more. ANOVA and linear regression were used for
      modelling aortic diameter as a continuum, while chi-square analysis and logistic
      regression were used in comparing men with and without the diagnosis of AAA.
      FINDINGS: By December 1998, of 19,583 men had been invited to undergo ultrasound
      screening for AAA, 12,203 accepted the invitation (corrected response fraction
      70.8%). The prevalence of AAA increased with age from 4.8% at 65 yr to 10.8% at
      80 yr (chi(2)=77.9, df=3, P<0.001). The median (IQR) diameter for the non
      aneurysmal group was 21.4 mm (3.3 mm) and there was an increase (chi(2)=76.0,
      df=1, P<0.001) in the diameter of the infra-renal aorta with age. Since 27 mm is
      the 95th centile for the non-aneurysmal infra-renal aorta, a diameter of 30 mm or
      more is justified as defining an aneurysm. The risk of AAA was higher in men of
      Australian (OR=1.0) and northern European origin (OR=1.0, 95%CL: 0.9, 1.2)
      compared with those of Mediterranean origin (OR=0.5, 95%CL: 0.4, 0.7).
      CONCLUSION: Although screening has not yet been shown to reduce mortality from
      AAA, these population-based data assist the understanding of aneurysmal disease
      and the further development and use of endoluminal grafts for this condition.

PMID- 11336847
TI  - Familial abdominal aortic aneurysms in the Otago region of New Zealand.
AB  - PURPOSE: To investigate the familial incidence and phenotypic characteristics of
      patients with abdominal aortic aneurysms (AAA) in the Otago region of New
      Zealand. METHODOLOGY: A retrospective audit based pilot study and a prospective
      study of patients having abdominal aortic aneurysm repair from September 1988 to
      September 1999 was performed. RESULTS: 248 probands were enrolled, of which 19.4%
      had one or more first degree relative affected. The age at diagnosis of the
      familial (70.2) and non-familial (70.5) patients was similar. The proportion of
      females was increased in the familial subgroup. Hypercholesterolaemia was the
      only phenotypic feature to differentiate familial from non-familial patients and
      was associated with an earlier age of presentation. In the familial families,
      brothers were the most common relative affected and 77% of the families had two
      patients with AAA. CONCLUSION: 19.4% of patients operated on in the Otago area
      for AAA had a familial component to their aneurysm.

PMID- 11336848
TI  - Results of 256 consecutive abdominal aortic aneurysm repairs using
      extraperitoneal approach.
AB  - Two hundred and fifty-six consecutive abdominal aortic aneurysms were repaired
      using three approaches for extraperitoneal exposure of the aorta and iliac
      vessels from February 1990 through September 1998. The perioperative mortality
      rate was 3.1% in 228 elective repairs and 14.3% in 28 ruptured cases. The initial
      23 cases were repaired using Sicard's method. The duration of endotracheal
      intubation was 1.0+/-2.8 h, alimentation initiation was 2.7+/-1.6 days, and
      narcotic requirements were 1.2+/-1.1 times. Following these initial cases, we
      employed Williams' method for 192 abdominal aneurysms, however; repeated
      incisional pain and three cases of deforming bulge led us to avoid dividing
      muscles. In the last 13 cases, our approach was performed without muscle
      dividing. The narcotic requirements decreased to 0.3+/-0.7 times. As for
      postoperative complications, the larger skin incision approach had no shower
      embolism. However, the shorter skin incision had four cases of shower embolisms,
      one lymphorrhea and one vascular trauma by the aortic clamp. The extraperitoneal
      approach offers certain physiologic advantages with minimal disturbance of
      gastrointestinal and respiratory function. We believe that this method is useful
      for rapid approach to the proximal aorta in case of emergency. Postoperative
      wound complications could be prevented via an oblique incision without muscle
      dividing.

PMID- 11336849
TI  - Using postoperative cardiac Troponin-I (cTi) levels to detect myocardial
      ischaemia in patients undergoing vascular surgery.
AB  - BACKGROUND: Cardiac complications occur commonly in vascular surgery patients.
      Diagnosis of cardiac complications is difficult because of the inaccuracies
      associated with traditional cardiac enzyme measurements. CTi, a highly sensitive
      and specific marker of myocardial injury, may be able to detect cardiac
      complications with greater ease and accuracy. METHODS: The study prospectively
      examined 100 consecutive patients who underwent major vascular surgery between
      6/7/98 and 31/12/98 at the Royal Brisbane Hospital. Daily measurements of cTi,
      creatine kinase (CK), creatine kinase MB (CKMB), CKMB index, renal function and
      haemoglobin were taken for three postoperative days. One postoperative
      electrocardiograph (ECG) was taken. An extensive cardiac history was taken.
      Intraoperative and postoperative events were recorded. FINDINGS: There were 100
      patients. 18 patients (18%) had a cTi elevation. On the basis of classical
      diagnostic criteria, 15 patients (15%) suffered one or more cardiac complication
      (either myocardial infarction, congestive cardiac failure, unstable angina or
      atrial fibrillation). One patient (1%) who had a cTi elevation died. CTi
      elevation occurred in five patients (5%) who were not diagnosed with cardiac
      complications based on traditional criteria. Despite not meeting specific
      diagnostic criteria for cardiac complications, all patients showed signs and
      symptoms that could be attributed to myocardial ischaemia. Every patient who
      developed congestive cardiac failure or atrial fibrillation had a cTi elevation.
      A Chi-square analysis revealed a significant association between cTi elevation
      and postoperative cardiac complications. Four variables contributed small but
      significant amounts of unique variance to the prediction of peak cTi on linear
      regression analysis. These were peak CKMB index, postoperative congestive cardiac
      failure, postoperative chest pain and postoperative cardiac complications.
      CONCLUSIONS: Routine cTi monitoring of postoperative vascular patients would be
      an effective and inexpensive way to detect patients with cardiac complications.
      The relationship between postoperative cTi elevation and significant coronary
      artery disease remains to be shown.

PMID- 11336850
TI  - Endovascular treatment of type B aortic dissections.
AB  - The purpose is to describe our experience with endovascular treatment of type B
      aortic dissections. Five patients were treated for complications following type B
      dissections like, false channel aneurysm formation, rupture and arterial
      obstruction. They were treated in general anaesthesia using a 'homemade'
      endoprosthesis or a commercially available endoprosthesis (Excluder) deployed
      during fluoroscopy. The patients have been followed at regular intervals with a
      median observation time of 18 months (range 12--36). One patient needed a
      secondary intervention due to dislodgement of the proximal stentgraft with
      haemorrhage into both the false and the true lumen. Otherwise there have been no
      early or late mortality or major complications in this series. Even if our
      experience with endovascular treatment of type B dissections is rather limited,
      the results so far are promising. Open surgery in many of these cases is
      complicated with high morbidity and mortality rate and the endovascular technique
      offers great advantages. A longer follow-up period is necessary to define the
      place of endovascular treatment.

PMID- 11336851
TI  - Mitral and mitro-aortic valve replacement with Sorin Bicarbon valves compared
      with St. Jude Medical valves.
AB  - OBJECTIVE: We assessed the clinical results of two bileaflet mechanical valves:
      the St. Jude Medical (SJM) and the Sorin Bicarbon (Sorin Bicarbon) used either in
      single mitral valve replacement (MVR) or in double, aortic and mitral, valve
      replacement (DVR). METHODS: Between September 1990 and November 1995, 217
      patients received either a St. Jude Medical (n=134) or a Sorin Bicarbon (n=86):
      136 mitral valve replacement with 83 St. Jude Medical and 53 Sorin Bicarbon and
      84 double valve replacement with 51 St. Jude Medical and 33 Sorin Bicarbon. There
      was no difference between both St. Jude Medical and Sorin Bicarbon cohorts in
      respect of mitral valve physiopathology, etiology of valve disease, associated
      lesions, echocardiographic and hemodynamic data. The only significant
      preoperative difference was the age of patients within the double valve
      replacement group and the size of implanted valves within the mitral valve
      replacement group. Follow-up was 100% complete with a mean of 39+/-18 months,
      ranging between 6 and 68 months. The total follow-up was 657 patient-years (pt
      y): 396 pt-y in the mitral valve replacement group and 274 pt-y in the double
      valve replacement group. RESULTS: Hospital mortality (St. Jude Medical: 2.2%;
      Sorin Bicarbon: 6.9%) and late mortality (St. Jude Medical: 8.4%; Sorin Bicarbon:
      6.3%) were not significantly different. Ten deaths were considered valve-related
      (St. Jude Medical 6, Sorin Bicarbon 4). The estimated 4-yr overall survival,
      including hospital mortality, was for St. Jude Medical--mitral valve replacement:
      89+/-4% and St. Jude Medical--double valve replacement: 93+/-4%, and for Sorin
      Bicarbon--mitral valve replacement: 87+/-5% and Sorin Bicarbon--double valve
      replacement: 91+/-5%. The linearized incidence (% per pt-y) of valve-related
      complications was 6.39 in the St. Jude Medical cohort and 9.2 in the Sorin
      Bicarbon cohort. The linearized incidence (% pt-y) of the prevalent complication,
      valve thromboembolism and bleeding, was for St. Jude Medical-mitral valve
      replacement: 3.41, St. Jude Medical--double valve replacement: 3.16 and for Sorin
      Bicarbon--mitral valve replacement: 2.17 and Sorin Bicarbon--double valve
      replacement: 3.67. The differences between each group of an estimated 4-yr
      freedom from combined thromboembolism and bleeding were not significant (St. Jude
      Medical--mitral valve replacement: 90+/-4%, St. Jude Medical--double valve
      replacement: 84+/-6%, and for Sorin Bicarbon--mitral valve replacement: 94+/-3%
      and Sorin Bicarbon--double valve replacement: 75+/-17%). CONCLUSIONS: In this
      clinical non-randomized study, there was no evidence of any significant
      difference between St. Jude Medical and Sorin Bicarbon valves over a 4-yr follow
      up.

PMID- 11336852
TI  - Microperfusion enhancement after TMLR in chronically ischemic porcine hearts.
AB  - OBJECTIVE: The purpose of this study was to determine the effect of
      transmyocardial laser revascularization (TMLR) on myocardial perfusion and
      function in chronically ischemic myocardium. METHODS: In the first operation a
      stenosis of the left anterior descending artery was created in 20 open-chest
      anesthetized pigs to implement this ischemic model. In contrast, four pigs served
      as controls (thoracotomy only). Seven days later (2nd operation), all animals
      were studied at baseline by analyzing different parameters of perfusion
      (radioactive microspheres), function, and intramyocardial pressure. Afterwards,
      pigs who received a left anterior descending artery stenosis were randomized into
      one of three groups: animals in laser group 1 (n=7) received one and in laser
      group 2 (n=7) two laser channels per cm(2) in the left anterior descending artery
      territory. Animals of the ischemic group (n=6) underwent the same procedures
      without transmyocardial laser revascularization. Three months later, the animals
      were re-studied (3rd operation) and additional analysis of histochemistry and
      myocardial water content was performed. RESULTS: Regional myocardial blood flow
      (RMBF) in laser group 2 revealed statistically higher RMBF values compared to the
      ischemic group (0.39+/-0.13 versus 0.14+/-0.12 ml/min/g; P=0.043), after 3
      months, whereas the absolute RMBF had not increased compared to the 1-week
      baseline values. Left ventricular stroke work index (LVSWI) at rest and under
      stress did not show any improvement compared to the initial values in all study
      groups (P=ns). Nevertheless, laser group 1 demonstrated relatively higher
      LVSWI(max) values compared to the ischemic (1.33+/-0.19 versus 0.93+/-0.16 mJ/kg;
      P=0.03) and laser group 2 (1.33+/-0.19 versus 1.02+/-0.15; P=0.024). Regional
      contractility of laser groups 1 and 2 recovered after 3 months (which had
      deteriorated shortly after transmyocardial laser revascularization) and increased
      under stress (100% versus 144.33+/-46.42, P=0.029 and 100% versus 116.26+/-21.06,
      P=0.034; respectively). In contrast, the corresponding ischemic group values were
      not different from initial values (P=ns). CONCLUSIONS: This model of chronic
      regional ischemia demonstrates that CO(2)-laser revascularization significantly
      improves microperfusion and regional function, whereas the overall perfusion and
      global LV function is unchanged.

PMID- 11336853
TI  - Surgical repair of anomalous origin of the coronary artery from the pulmonary
      artery in children.
AB  - OBJECTIVE: To evaluate surgical management of children with coronary artery
      anomalies, including patients with rare abnormalities (left anterior descending
      artery or right coronary artery originating from the pulmonary artery). METHODS:
      A retrospective review of eight patients (aged 2 months--10 yr; median 3.5 yr),
      treated for coronary artery anomalies between 1989 and 1999. Coronary vessels
      were reimplanted to the aorta in four children, while the remaining four were
      subjected to the Takeuchi procedure. RESULTS: All children survived. None
      required mechanical circulatory support. In six patients significant mitral valve
      insufficiency developed, nevertheless, no intraoperative mitral valvuloplasty was
      performed. Follow-up was 2 months--10 yr. All patients developed normally and are
      currently in NYHA class I. Echocardiography revealed normal FS and EF values
      within 1--17 months postoperatively. CONCLUSIONS: In children with coronary
      artery anomalies, the best results are achieved with an early diagnosis and
      aggressive management. In our opinion coronary vessel reimplantation and the
      Takeuchi procedure yields comparable results.

PMID- 11336854
TI  - Aortic repair in Marfan's syndrome: prevention of mechanical leaflets damage.
AB  - Aortic incompetence in Marfan's syndrome results from distortion or dilatation of
      the sinuses of Valsalva, annuloaortic ectasia or a combination of these problems.
      Valve leaflets in these patients are macroscopically normal in spite of aortic
      insufficiency. Replacement of the ascending aorta, root and aortic valve with a
      composite graft was, for a long time, the treatment of choice for Marfan
      patients. Valve-preserving procedures (remodeling or reimplantation) provide the
      advantages of avoiding the shortcomings of standard surgical techniques, and
      maintaining the functional integrity of the left ventricular (LV) outflow tract,
      aortic root and ascending aorta. We developed a modified valve-sparing
      reimplantation technique for avoiding leaflet damage. This was achieved by
      leaving a 'cushion' of aortic wall (8--10 mm) that, sewn on the Dacron graft,
      works as a 'damper' and prevents leaflets injury during the systolic opening of
      the valve. For final judgment of this operative method long-term results are
      necessary.

PMID- 11336856
TI  - Women's voices, women's experiences--taking the time to listen.

PMID- 11336857
TI  - Women's health issues across the lifespan.
AB  - This study examines differences and similarities in women's health status, health
      care needs, and access to care across age groups. Data are from the Commonwealth
      Fund 1998 Survey of Women's Health. Several age-group specific issues stand out,
      such as more limited access to health insurance and a usual source of care among
      younger women, the emergence of chronic health care problems among women in the
      45-64 age group, and the presence of multiple health problems among elderly
      women. The analyses reveal several themes that cut across age groups, such as the
      relationship between poverty and health status, the importance of health
      insurance, and the generally limited receipt of physician information about
      health-related behaviors.

PMID- 11336858
TI  - The influence of income, education, and work status on women's well being.
AB  - This article, based on data from the Commonwealth Fund 1998 Survey of Women's
      Health, examines the relationship between socioeconomic status (SES) and women's
      health. Women living in poverty are less likely than their higher-income
      counterparts to have health insurance and use preventive services, and more
      likely to have access problems, suffer from chronic illnesses, and report low
      overall health scores. Women with low educational attainment are also less likely
      to have health insurance and to use preventive services, and more likely to
      report poorer health status than women with a college education. We conclude with
      implications for public policy.

PMID- 11336859
TI  - Motherhood, health status, and health care.
AB  - This study examines the impact of multiple roles and stressors on women of
      childbearing age, and compares the health status of women with and without
      children and their ability to access health care. Motherhood has many complex
      interactions with income level, availability of health insurance, and available
      social and income support. A cumulative burden of multiple stressors (eg, being
      poor, uninsured, less educated, employed full-time, or being a single mother)
      relates to worse health status, levels of depression, and opportunities for
      obtaining health care. Multiple stressors seem to have a stronger effect on
      mothers than on nonmothers. Research should focus on identifying vulnerable
      groups and combinations of stressors for women both with and without children,
      and how to mitigate adverse impacts on physical and mental health.

PMID- 11336860
TI  - Caregiving: challenges and implications for women's health.
AB  - Informal and unpaid care is an integral feature of the U.S. health care system
      for the nation's sick, disabled, frail, and terminally ill. Much of what we know
      about caregiving is based on interviews with caregivers and, in some cases, care
      recipients. Prior studies have either not been based on a nationally
      representative sample or have collected very little information about non
      caregivers. This study, using the Commonwealth Fund 1998 Survey of Women's
      Health, uses a nationally representative sample of caregivers and non-caregivers
      to examine the health impact of providing informal and unpaid care, focusing
      primarily on women. Our findings indicate that caregivers experience double
      jeopardy. They are significantly more likely to be in poor health and to have
      experienced problems getting needed care. These findings suggest that it is time
      to explore alternative or complements to informal caregiving. They underscore the
      need to find more equitable ways to share caregiving costs and risk, and provide
      support to assist those who currently provide care.

PMID- 11336861
TI  - Managed care and women's health: access, preventive services, and satisfaction.
AB  - This paper examines insured women's access to health care, receipt of preventive
      services, and satisfaction with care by the types of health plans in which they
      are enrolled. Three types of plans are compared: managed care (HMOs and PPOs),
      fee-for-service with utilization controls, and traditional fee-for-service. For
      women who have been enrolled in their plans for at least one year, we find the
      same or better access to care in managed care plans as compared with other plans;
      receipt of more gender-specific clinical preventive services in managed care
      plans, but no differences among types of plans for non-gender-specific preventive
      services or counseling services; and lower satisfaction with care in managed care
      plans. The implications for practice and policy are discussed.

PMID- 11336862
TI  - Midlife women making hormone therapy decisions.
AB  - This study focuses on midlife women aged 40-65 years who were in transition to
      menopause, were menopausal or had a hysterectomy, to examine and better
      understand hormone therapy (HT) choices women make. Among the nationally
      representative sample of women in the Commonwealth Fund 1998 Survey of Women's
      Health (n = 884), 39% of the menopausal women reported current HT use. The two
      primary reasons for initiating HT are following a doctor's recommendation and
      seeking relief of menopausal symptoms. Age, education, race, hysterectomy status,
      having health insurance, use of calcium supplements and comfort in communicating
      with a doctor are important factors associated with HT use. This study
      underscores the importance of physicians and other health professionals providing
      accurate HT information to assist women in making HT decisions.

PMID- 11336863
TI  - Psychological distress, unmet need, and barriers to mental health care for women.
AB  - Using data from the Commonwealth Fund 1998 Survey of Women's Health, this article
      describes the characteristics of women in need of mental health services for
      depression or anxiety, and identifies factors related to why women do not get
      needed care. Depressive/anxiety symptoms are common and access to care for
      psychological distress remains a problem for many women, especially for
      minorities, those with less education, and those without a usual source of health
      care. Sources of unmet need include patient factors, clinician factors, and
      characteristics of the health system, such as costs of mental health care.

PMID- 11336864
TI  - Prevalence of violence and its implications for women's health.
AB  - This study estimates the lifetime prevalence of violent experiences and their
      relationship to health and the use of health services in U.S. women aged 18-64
      years. The Commonwealth Fund's 1998 Survey of Women's Health provides a
      nationally representative sample. Use of weighted data allows projections to be
      made to the U.S. population. Over four of ten women in the U.S. are likely to
      have experienced one or more forms of violence, including child abuse (17.8%),
      physical assault (19.1%), rape (20.4%), and intimate partner violence (34.6%). In
      multivariate logistic regression models that control for sociodemographic
      characteristics, violence-particularly intimate sexual violence-is significantly
      related to poorer physical and mental health and increased problems with access
      to medical care. Only one-third of women who experience violence have discussed
      it with a physician. Health care professionals need to initiate the conversation
      about violence and offer referrals for needed services.

PMID- 11336865
TI  - The "adolescence" of clinical research: a surgeon's view.

PMID- 11336866
TI  - Prevalence of acanthosis nigricans and its association with hyperinsulinemia in
      New Mexico adolescents.
AB  - PURPOSE: To determine whether the association between acanthosis nigricans (AN)
      and hyperinsulinemia is independent of obesity and other variables. METHODS: A
      convenience sample of 675 New Mexico middle school students was screened to
      determine the presence of AN, obesity, and other variables, including: ethnicity,
      parental history of diabetes, and level of physical activity. Fasting glucose and
      insulin levels were drawn on 233 students to determine the association between
      risk factors and hyperinsulinemia. RESULTS: Acanthosis nigricans (AN) was present
      in 18.9% of students screened. Twenty-one percent of the subsample had
      hyperinsulinemia. Based on these results, the estimated prevalence of
      hyperinsulinemia among all middle school students in New Mexico was 8.9%. Forty
      seven percent (47.2%) of students who had AN and were obese had hyperinsulinemia,
      compared with 2.4% of students who did not have either of these conditions. In
      multiple logistic regression analysis, AN and obesity were independently and
      positively associated with hyperinsulinemia, whereas physical activity was
      protective. CONCLUSIONS: The high prevalence of risk factors in this population
      makes diabetes prevention a priority for public health action. AN screening is an
      easily performed, noninvasive method for identifying adolescents at risk for type
      2 diabetes.

PMID- 11336867
TI  - Clinical and psychosocial factors associated with achievement of treatment goals
      in adolescents with diabetes mellitus.
AB  - PURPOSE: To examine the following questions with regard to the initiation of a
      new intensive management program for adolescents with Type 1 diabetes mellitus:
      (a) What clinical and psychosocial factors are associated with achievement of
      metabolic control treatment goals after 1 year? and (b) What baseline clinical
      and psychosocial factors are associated with improvement in the quality of life
      after 12 months? METHODS: Eighty-one subjects (of 83 who began; aged 14.3 +/- 2.0
      years at entry; 48 females, 33 males; 95% white; diabetes duration 8.9 +/- 3.9
      years) with Type 1 diabetes completed 12 months of follow-up in a study of
      intensified treatment of diabetes. Assessments at baseline and at 12 months used
      the Diabetes Quality of Life for Youth scale, the Self-efficacy for Diabetes
      Scale, the Children's Depression Inventory, the Issues in Coping with Diabetes
      Scale, and the Diabetes Family Behavior Scale. Data were analyzed using multiple
      and logistic regression. RESULTS: From a baseline of >9%, HbA1c levels decreased
      to a mean of 7.8 +/- 0.7%, with 30% of the subjects achieving our treatment goal
      of <or=7.2%. Logistic regression demonstrated that achievement of goal levels of
      HbA1c were associated with better metabolic control at study entry (p = .05),
      participation in coping skills training (p = .003), and more parental
      participation in guidance and control (p = .05). Multiple regression analysis
      demonstrated that participation in coping skills training with lower impact of
      diabetes on quality of life at baseline and less depression at baseline
      contributed significantly to the variance (0.57) in quality of life at 12 months.
      CONCLUSIONS: Providers need to pay particular attention to adolescents with
      poorer metabolic control and impact of diabetes on quality of life when they
      intensify their treatment because they are less likely to reach treatment goals.
      Furthermore, behavioral interventions such as coping skills training may help
      teens achieve their goals.

PMID- 11336868
TI  - Evaluation of a peaceful conflict resolution and violence prevention curriculum
      for sixth-grade students.
AB  - PURPOSE: To evaluate a Social Cognitive Theory-based violence prevention
      curriculum among sixth-grade students. METHODS: The evaluation was conducted
      using a quasi-experimental pretest-posttest control group design. Students were
      pretested 2 weeks before the intervention started and were posttested 2 weeks
      after it ended. The study was conducted in four middle schools serving children
      and adolescents living in or around public housing in a southeastern city. The
      participants included all sixth-grade students who were predominantly African
      American (88.7%), 41% lived in public housing, and 80% lived in homes with an
      employed head of household. The intervention schools had 292 students, and the
      control schools 412 students. The Peaceful Conflict Resolution and Violence
      Prevention Curriculum is a 13-module skills-building curriculum based on Social
      Cognitive Theory. It taught identification of situations that could result in
      violence; avoidance, confrontation, problem-solving, and communication skills;
      conflict resolution skills; the conflict cycle; the dynamics of a fight; and how
      to express anger without fighting. MAIN MEASURES: The primary outcome variable
      was a five-item scale assessing the frequency of fighting and weapon carrying
      behaviors (alpha =.72) and a scale measuring intentions to use violence in 11
      hypothetical situations (alpha = .81). Levels of exposure to violence and
      victimization (alpha = .82) and depression (alpha = .86) were also assessed. The
      data were analyzed with general linear modeling with repeated measures. RESULTS:
      At pretest, the intervention and control groups did not differ in gender, age,
      depression, exposure to violence, or any other demographic variable. A group x
      time interaction effect (p = .029) was found in the use of violence scale. From
      pretest to posttest there was a decrease in the use of violence by students in
      the intervention group and an increase in the use of violence in the control
      group. Most of the changes were accounted for by changes in the frequencies of
      carrying concealed guns and fighting resulting in injuries requiring medical
      treatment. A group x time interaction effect (p = .002) was also found for the
      intention to use violence scale. Students in the intervention group did not
      change their mean scores from pretest to posttest, whereas students in the
      control group increased in their mean intention to use violence scale scores.
      Neither interaction effect was influenced by gender, exposure to violence, or
      level of depression. CONCLUSION: The Peaceful Conflict Resolution and Violence
      Prevention curriculum appears to have positive short-term effects on self
      reported use of violence and intentions to use violence by these middle-school
      students.

PMID- 11336869
TI  - Reliability of adolescents' self-reported sexual behavior: a comparison of two
      diary methodologies.
AB  - PURPOSE: To evaluate techniques for measuring high-risk sexual behaviors by
      comparing the reliability and acceptability of two daily sexual behavior diary
      modes: a written calendar and an automated telephone interview. METHODS: This
      randomized controlled study included 105 sexually active female adolescents aged
      15-19 years recruited from among teens seeking reproductive health care services
      at a family planning clinic in the San Francisco Bay Area. Participants completed
      a standardized sexual behavior questionnaire each day for 4 weeks. Contraceptive
      use by method type was recorded. Reporting differences between the two diary
      modes were assessed using generalized estimating equations, concordance of diary
      and retrospective interview responses was evaluated using kappa statistics, and
      contingency table analysis and Poisson regression models were constructed to
      examine mode acceptability. RESULTS: Respondents randomized to the telephone
      diary cohort reported less frequent use of barrier contraceptive methods,
      specifically less spermicide use (odds ratio 0.27, 95% confidence interval 0.08,
      0.95), and decreasing male condom use over time, whereas reports of male condom
      use increased for written diary respondents (p = .007). Participant
      characteristics associated with diary acceptability, defined as the frequency of
      diary completion, were assessed and teens classified as higher risk provided
      fewer diary reports (p < .01). Regardless of mode completed, 65% of respondents
      believed the telephone diary would be preferable to the written diary for most
      teens. CONCLUSIONS: The automated telephone diary offered an acceptable, even
      preferred, methodologic alternative to the written diary calendar and elicited
      more accurate reporting of selected contraceptive behavior.

PMID- 11336870
TI  - Personal values and sexual decision-making among virginal and sexually
      experienced urban adolescent girls.
AB  - PURPOSE: To guide the development of an intervention to reduce the incidence of
      sexually transmitted diseases (STDs) in urban, adolescent girls, we investigated
      such girls' reasons for deciding to have or not to have sexual intercourse.
      METHODS: Consecutive girls >or=14 years of age attending an urban adolescent
      clinic were invited to complete an anonymous survey about sexual decision-making.
      In this pilot study, girls were asked: (a) whether they agreed with a statement
      that they had or had not had sexual intercourse "because of my values and
      beliefs"; and (b) to select from a list one or more specific reasons why they had
      or had not had intercourse. The girls were categorized by self-report as either
      "virgins," "currently inactive" (no intercourse in the preceding 3 months), or
      "currently active" (had intercourse during the preceding 3 months). RESULTS:
      Usable surveys were obtained from 197 adolescents whose age (18.2 +/- 2.6 years)
      and race (69% black) were comparable to those of clinic attendees in general.
      Forty girls (20%; age 16.1 +/- 2.1 years) were virgins, 25 girls (13%; age 17.8
      +/- 2.3 years) were inactive, and 132 girls (67%; age 18.9 +/- 2.5 years) were
      currently active. "Values and beliefs" were cited as the reason for decisions
      about sexual behavior by 53% of the virgins, but only by 24% of the sexually
      inactive and 24% of the sexually active girls (p = .002). Virgins were more
      likely than inactive girls to cite three specific reasons for not having sex:
      "not the right thing for me now" (82% vs. 50%, p = .007), "waiting until I am
      older" (69% vs. 8%, p = .001), and "waiting until I am married" (67% vs. 38%, p =
      .02). The reason "against my religious beliefs" was cited by 23% of virgins and
      13% of inactive girls (p = not significant). Personal values were implicit in the
      two specific reasons for having sex that active girls chose most frequently,
      namely, "I like/love the person" (86%) and "I like having sex" (37%), although
      only 24% of these girls had explicitly cited "values and beliefs" as their reason
      for having sex. CONCLUSIONS: Our data indicate that urban girls, both those who
      have had sexual intercourse and those who have not, view their sexual behavior as
      being based on personal (although infrequently religious) values. Many of the
      virginal urban, adolescent girls we surveyed hold abstinence as a personal value.
      The sexually active adolescents perceive the decision to have sexual intercourse
      as being based affirmatively on their personal values rather than on the chance
      occurrence of opportunities to have intercourse. These data may be useful in the
      development of new strategies for reducing urban adolescent girls' risk of
      acquiring sexually transmitted diseases.

PMID- 11336871
TI  - Correlates of using dual methods for sexually transmitted diseases and pregnancy
      prevention among high-risk African-American female teens.
AB  - PURPOSE: To identify correlates of consistent dual-method use among African
      American female adolescents at risk of sexually transmitted diseases (STDs) and
      pregnancy. METHODS: A convenience sample of 522 sexually active female teens
      attending adolescent medicine clinics, health department clinics, and school
      health classes volunteered. Recruitment sites were in low-income neighborhoods of
      Birmingham, Alabama. Adolescents completed a questionnaire and a face-to-face
      interview and provided vaginal swab specimens for laboratory diagnosis of STDs.
      Those reporting use of condoms and at least one other method of contraception,
      for each of the last five occasions they had sex were classified as consistent
      dual-method users. The questionnaire assessed frequency of adolescents'
      communication with their parents and partners about sex. The questionnaire also
      assessed two measures of parental supervision and adolescents' desire to avoid
      pregnancy. Multiple logistic regression assessed the independent contribution of
      each correlate of consistent dual-method use. RESULTS: Seventy-one adolescents
      (13.6%) were classified as consistent dual-method users. A strong desire to avoid
      pregnancy was the most influential correlate of consistent dual-method use [odds
      ratio (OR) =2.3]. Adolescents reporting that their parents generally knew whom
      they were with (OR = 2.0) and those reporting more frequent communication with
      parents (OR = 1.9) were also more likely to be consistent dual users. CONCLUSION:
      The findings suggest the need for research to examine the efficacy of
      interventions building on adolescent females' desire to avoid pregnancy. Study
      findings also suggest that interventions promoting improved parent-adolescent
      communication and improved parental supervision may contribute to adolescents'
      use of dual methods for STD and pregnancy prevention.

PMID- 11336872
TI  - Perceived versus actual knowledge about correct condom use among U.S.
      adolescents: results from a national study.
AB  - PURPOSE: To assess the prevalence of three misconceptions about correct condom
      use and determine whether prevalence of these misconceptions varied by gender,
      sexual intercourse experience, experience using condoms, and the relationship
      between adolescents' actual and perceived knowledge about correct condom use.
      Variables that predicted misconceptions about correct condom use were also
      identified. METHODS: Data from the National Longitudinal Study of Adolescent
      Health were analyzed to determine prevalence of misconceptions among 16,677
      adolescents. Misconceptions were: (a) no space at the tip of the condom, (b)
      Vaseline can be used with condoms, and (c) lambskin protects against the acquired
      immunodeficiency virus better than latex. Chi-square analyses determined
      differences in prevalence of misconceptions between male and female adolescents
      based on their sexual and condom use experience as well as their level of
      perceived knowledge about correct condom use. Logistic regression models
      identified predictors of reporting misconceptions. RESULTS: Depending on
      intercourse experience and experience using condoms, about one-third to one-half
      believed the first two misconceptions and about one-fifth believed the latter
      one. Perception of knowledge about correct condom use was infrequently related to
      actual knowledge. Misconceptions were less likely among older adolescents, those
      ever having intercourse, those reporting four or more lifetime intercourse
      partners, those who had used condoms, females, and those not reporting a
      religious affiliation. CONCLUSIONS: Misconceptions about correct condom use are
      common among adolescents. Sexually active adolescents need more complete
      information about correct condom use.

PMID- 11336873
TI  - Condom use self-efficacy: effect on intended and actual condom use in
      adolescents.
AB  - PURPOSE: To investigate aspects of adolescents' condom use self-efficacy that
      affect their intended and actual condom use. METHODS: Four hundred twenty-four
      male and female sexually experienced and inexperienced adolescents with a mean
      age of 17.0 years filled out a questionnaire concerning condom use self-efficacy
      and intended and actual condom use. Specific condom use self-efficacy scales were
      constructed from 37 items on the basis of a principal component analysis. The
      effect of self-efficacy, both as a global measure and in terms of specific
      scales, on condom use intention and consistency was assessed using multiple
      hierarchic regression analyses. RESULTS: Six specific self-efficacy scales were
      constructed: Technical Skills, Image Confidence, Emotion Control, Purchase,
      Assertiveness, and Sexual Control. In sexually inexperienced adolescents, global
      self-efficacy explained 48%, the six self-efficacy scales 30%, and both together
      51% of the variance in intention, after statistical control for gender, age, and
      education level. In the sexually experienced sample, this was 40%, 50%, and 57%
      for intention, and 23%, 29%, and 33% for consistency of condom use. Significant
      predictors of intention in the final model were gender, age, global self-efficacy
      and purchasing skills in the inexperienced sample, and global self-efficacy,
      emotion control, assertiveness, image confidence, and sexual control in the
      experienced sample, whereas gender, age, global self-efficacy, emotion control,
      assertiveness, and purchase predicted consistency of condom use in the
      experienced sample. CONCLUSIONS: Condom use self-efficacy is a multidimensional
      construct. Intended and actual condom use in adolescents are best predicted by
      self-efficacy measures that include both global and relevant specific aspects of
      condom use.

PMID- 11336875
TI  - Programming of endocrine mechanisms of cardiovascular control and growth.
AB  - Several epidemiologic studies have linked size at birth to health in adult life.
      One school of thought centers on the part that periconceptual or intrauterine
      events play in this relationship. The idea is that an event, or several events,
      during critical periods of development can program, or permanently alter, fetal
      physiology resulting in altered size at birth and subsequent adult disease,
      including that of the cardiovascular system. Maternal diet or body composition at
      the time of conception can influence placental development and subsequent
      transfer of nutrients and substrates to the fetus. Alterations to the maternal
      diet or body composition throughout gestation are then seen as challenges that
      are superimposed on this backdrop of periconceptual events. One task is to find
      an animal model that replicates the major features of the epidemiologic data: for
      adult cardiovascular disease this would be altered fetal size and the development
      of postnatal hypertension. In addition, a critical issue is to investigate the
      mechanisms underlying this Fetal Origins of Adult Disease hypothesis. The
      multiple mechanisms that constitute fetal cardiovascular responses to hypoxia in
      late gestation at neuronal, endocrine, and local tissue levels have been studied
      extensively, and there is evidence from several different experimental paradigms
      that these control mechanisms can be programmed by intrauterine challenges. This
      review synthesizes the current knowledge in this area and considers how the
      programming of cardiovascular control relates to fetal growth.

PMID- 11336876
TI  - Increase in prostaglandin H synthase 2, but not prostaglandin F2alpha synthase
      mRNA in intrauterine tissues during betamethasone-induced premature labor and
      spontaneous term labor in sheep.
AB  - OBJECTIVE: Prostaglandin F synthase (PGFS) catalyzes reduction of prostaglandin
      H(2) to PGF2alpha. No information exists on PGFS expression and regulation during
      pregnancy, either mRNA or protein, in relation to labor in uterine tissues in any
      species. We characterized PGFS mRNA expression in ovine myometrium, endometrium,
      maternal and fetal placenta in betamethasone-induced premature labor and
      spontaneous term labor using our cloned ovine PGFS riboprobe. Prostaglandin H
      synthase (PGHS) 2 mRNA was evaluated simultaneously as a control whose pregnancy
      related changes are well known. METHODS: Poly-A or total RNA from fetal placenta,
      myometrium, and endometrium in control ewes at 143-147 days of gestational age
      (dGA, TCNL, n = 6), and ewes in spontaneous term labor at 145-147 dGA (STL, n =
      6) and endometrium and maternal and fetal placenta in early control ewes not in
      labor (ECNL, n = 6) and betamethasone induced labor at 128-135 dGA (BL, n = 6)
      were analyzed for PGHS2 and PGFS mRNA. RESULTS: PGFS mRNA did not change at
      spontaneous term labor in myometrium, endometrium, and fetal placenta. PGFS mRNA
      decreased during betamethasone-induced premature labor in endometrium and
      maternal placenta (P < .05), but remained unchanged in fetal placenta and
      myometrium. PGHS2 mRNA increased in endometrium, placenta, and myometrium during
      betamethasone-induced premature labor and spontaneous term labor. CONCLUSION:
      Increased PGHS2, but not PGFS mRNA was tightly associated with the onset of
      betamethasone-induced premature labor as well as spontaneous term labor in the
      endometrium, placenta, and myometrium. Transcription of PGFS mRNA may not be the
      rate-limiting step in the pathway contributing to increased PGF(2alpha) at labor.

PMID- 11336877
TI  - Expression of vascular endothelial growth factor in third-trimester placentas is
      not increased in growth-restricted fetuses.
AB  - OBJECTIVE: Vascular endothelial growth factor (VEGF) is considered the growth
      factor that stimulates vasculogenesis and angiogenesis. Recent studies have
      demonstrated its role in regulating placental growth and invasion. Its expression
      can be upregulated by hypoxia. Intrauterine growth restriction (IUGR) is thought
      to be associated with inadequate placental perfusion, which might result from a
      failure in the development of the villous vascular network. Our present study was
      undertaken to examine the relationship between VEGF expression and IUGR in
      pregnancies with preserved umbilical artery end-diastolic flow. METHODS: VEGF
      Expression was determined by immunohistochemical analysis of placentas from 17
      pregnancies with normal infant birth weight and 17 pregnancies complicated by
      IUGR. RESULTS: We found no significant differences in the expression of VEGF in
      villous syncytiotrophoblasts and intermediate trophoblasts in maternal decidua
      between IUGR and normal pregnancies. However, in both groups there was a strong
      correlation in the expression of VEGF with villous syncytiotrophoblasts and
      intermediate trophoblasts. In normal and IUGR pregnancies the infants' Apgar
      scores at birth were significantly correlated with VEGF staining in both
      syncytiotrophoblasts and intermediate trophoblasts (P < .05). A strong
      correlation also was found between cord hematocrit and VEGF staining in villous
      syncytiotrophoblasts (P < .05), but VEGF staining in intermediate trophoblasts
      was not correlated with cord hemoglobin or hematocrit. CONCLUSIONS: Our results
      suggest that VEGF acts in an autocrine and paracrine fashion in both normal and
      IUGR placentas, and its expression can have an effect on the well being of the
      infant at birth.

PMID- 11336878
TI  - Lack of effect of psychosocial stress on maternal corticotropin-releasing factor
      and catecholamine levels at 28 weeks' gestation.
AB  - OBJECTIVE: Corticotropin-releasing factor (CRF) and catecholamines are among the
      major hormones activated during the adaptive response to stressful stimuli. In
      pregnant women, serum CRF and catecholamines levels increase during labor and
      preterm delivery. The aim of the present study was to evaluate whether
      psychosocial stress measures are correlated with serum CRF or urinary
      catecholamine [ie, epinephrine, norepinephrine (NE), dopamine (DA)] levels in
      healthy midtrimester pregnant women. METHODS: A large group of white pregnant
      women (n = 382) participated in the present study. The Work Conditions
      Questionnaire and the Psychiatric Epidemiology Research Interview were
      administered to measure job stress and general life stress, respectively. Urine
      and blood specimens were collected at 28 weeks of gestation at the time of
      psychosocial evaluation. Epinephrine, NE, and DA were quantified in the urine by
      a highly sensitive method based on an amperometric detector. Serum CRF and
      cortisol levels were measured in blood specimens by using specific
      radioimmunoassays. RESULTS: Serum CRF and cortisol levels did not vary between
      patients with high and low scores on psychological tests, and no correlation was
      found between CRF and cortisol levels. One job stress measure, low job latitude,
      was significantly associated with a mild increase in NE and DA levels in the
      afternoon and night (P < .05, analysis of variance). Serum cortisol levels were
      inversely correlated with NE in the morning (r = -0.447; P =.002) and night
      segments (r = -0.391; P = .007) and with DA in the night period (r = -0.367; P =
      .013). CONCLUSION: The absence of a significant relationship between CRF/cortisol
      and psychosocial stress measures in pregnant women suggests that the hypothalamic
      pituitary-adrenal response to psychosocial stress may be masked at midtrimester
      by the constantly high levels of placental CRF, whose control is beyond the
      influence of environmental stressors.

PMID- 11336879
TI  - Decreased maternal serum leptin in pregnancies complicated by preeclampsia.
AB  - OBJECTIVE: To determine whether circulating levels of leptin differed between
      women with preeclampsia and women who had an uncomplicated pregnancy. METHODS:
      Maternal and umbilical venous plasma leptin concentrations obtained at delivery
      were compared in 36 pairs of women with either preeclampsia or normal pregnancy,
      matched 1:1 for prepregnancy body mass index and fetal gestational age at
      delivery. RESULTS: Prepregnancy body mass index was 21.1 +/- 2.1 kg/m2 in either
      study group (range 17.6-25.3 kg/m2 and 17.7-25.3 kg/m2 in the normal and
      preeclamptic group, respectively). Mean fetal gestational age at delivery was
      40.1 +/- 1.3 weeks and 40.1 +/- 1.2 weeks in the normal and preeclamptic group,
      respectively. Median leptin concentrations were significantly lower (P <.0001) in
      women with preeclampsia (8.3 ng/mL, range 3.5-20.0 ng/mL) than in normal pregnant
      women (20.2 ng/mL, range 6.0-63.7 ng/mL). Median umbilical venous leptin was not
      significantly different between groups (preeclampsia 11.8 ng/mL, range 2.0-37.2
      ng/mL; normal 7.6 ng/mL, range 1.6-24.3 ng/mL; P = .377). Umbilical venous leptin
      levels correlated positively with birth weight in both groups (preeclampsia rho =
      0.501, P = .002; normal rho = 0.517, P = .001), whereas no correlations were
      found between maternal and fetal hormone concentrations. Maternal leptin
      concentrations did not correlate with birth weight. CONCLUSION: Our data suggest
      that the correlation between umbilical venous leptin concentration and birth
      weight is independent of the presence of preeclampsia. Given the inconsistency in
      literature concerning circulating leptin levels in preeclampsia, further studies
      should investigate the regulatory systems of leptin in preeclampsia.

PMID- 11336880
TI  - Umbilical venous leptin concentration and gender in newborns.
AB  - OBJECTIVE: To investigate the relationship between umbilical venous leptin
      concentration and gender in 20 pairs of newborns matched 1:1 for birth weight and
      gestational age at sampling. MATERIALS: Blood samples were obtained from 40 women
      at delivery, identified as having an uncomplicated pregnancy. Umbilical venous
      blood samples were obtained from their newborns (20 males and 20 females) at
      birth. Specimens were analyzed using a human leptin 125-I radioimmunoassay.
      RESULTS: Fetal leptin correlated positively with birth weight (rs = 0.541; P <
      .001). Umbilical venous leptin concentrations in female newborns (median: 10.7
      ng/mL, range: 3.5-34.4 ng/mL) were significantly higher (P = .028) than in male
      newborns (median: 7.7 ng/mL, range: 2.0-19.3 ng/mL). There was no significant
      correlation between maternal and fetal leptin concentrations. Multiple logistic
      regression analysis revealed birth weight and gender to be independent factors
      influencing fetal cord leptin. CONCLUSION: Our results suggest that in the fetus,
      as in children and adults, gender and weight are the major determinants of
      circulating leptin levels.

PMID- 11336881
TI  - Hormone replacement reduces elevated in vivo venous tone in hypertensive
      ovariectomized rats.
AB  - OBJECTIVE: The venous system may play a role in the development and progression
      of postmenopausal hypertension. In the present study, we investigated the effect
      of chronic angiotensin II-induced hypertension on the geometric, elastic, and
      contractile properties of the saphenous vein in sex hormone deficient and
      replaced female rats. METHODS: Thirty Sprague-Dawley rats were ovariectomized (n
      = 10), ovariectomized and angiotensin-infused (n = 10), or ovariectomized plus
      angiotensin-infused and hormone replaced with estradiol and medroxyprogesterone
      (n= 10). After 4 weeks, the saphenous veins were removed and cylindrical segments
      of the vessels were placed into a microangiograph and cannulated at both ends.
      Intraluminal pressure versus outer diameter curves were registered in Krebs
      Ringer solution, in maximal norepinephrine contraction, and in full papaverine
      relaxation. RESULTS: In vivo venous tone of the saphenous vein in ovariectomized
      plus angiotensin-infused animals was significantly higher than in ovariectomized
      animals without angiotensin treatment (27.2 +/- 3.7% versus 5.3 +/- 2.1%,
      respectively; P <.05). Hormone replacement restored venous tone (9.6 +/- 3.4%; P
      <.01). In vitro pressure-induced myogenic tone was markedly reduced by chronic
      angiotensin infusion, which was partially reversed by hormone replacement.
      Passive incremental distensibility was lowered after angiotensin infusion
      independently of the sex hormone state. CONCLUSION: Hormone replacement improved
      venous contractility (rapid adaptation response), which was seen as decreased in
      vivo venous tone, but venous distensibility (chronic adaptation) was not improved
      by hormone replacement in our short-term study. We demonstrate beneficial short
      term effects of hormone replacement on the venous system in our model of
      postmenopausal hypertension. Further studies might be warranted to see whether
      long-term benefits can be achieved.

PMID- 11336883
TI  - RU-486 can abolish glucocorticoid-induced increases in CSF-1 receptor expression
      in primary human breast carcinoma specimens.
AB  - OBJECTIVE: We present the results of the application of organ culture techniques
      previously described in this journal to the study of steroid hormone
      responsiveness of primary breast carcinoma specimens. METHODS AND RESULTS: Nearly
      all breast carcinomas that express macrophage colony-stimulating factor-1R (CSF
      1R) at tissue harvest (15 of 18) had levels of CSF-1R expression lowered after
      incubation in steroid-free media. The decrease in CSF-1R expression was reversed
      by treatment with glucocorticoids; this glucocorticoid-induced increase in CSF-1R
      expression can be blocked by mifepristone (RU-486), a competitive inhibitor of
      glucocorticoid action. CONCLUSION: These results demonstrate that steroid hormone
      responsiveness of primary breast carcinomas can be assayed in vitro, a result
      which can not only be employed to better predict the responsiveness of breast
      carcinomas to therapies with steroid hormone agonists and antagonists, but also
      suggests that the therapeutic utility of mifepristone in breast cancer deserves
      further study.

PMID- 11336882
TI  - Relationship between expression of coactivators and corepressors of hormone
      receptors and resistance of ovarian cancers to growth regulation by steroid
      hormones.
AB  - OBJECTIVE: To determine whether aberrant expression of hormone receptor
      corepressors or coactivators or defects in estrogen receptor-mediated
      transcription might underlie resistance of ovarian cancers to hormonal therapy.
      METHODS: Northern analysis, Western analysis, and polymerase chain reaction were
      used to examine expression of estrogen receptor (ER), progesterone receptor (PR),
      the nuclear receptor corepressors N-CoR and SMRT, and the steroid receptor
      coactivator BRG-1 in ovarian cancer cell lines and primary cancers. The effect of
      BRG-1 transfection on ER-mediated transcription was examined. We also determined
      the effect of estrogen and the pure estrogen antagonist ICI 182,780 on cell cycle
      profile and expression of ER. Finally, we examined the ability of estrogen to
      upregulate expression of known estrogen-responsive genes. RESULTS: Among primary
      ovarian cancers, 18 of 52 (35%) expressed N-CoR, and 37 of 52 (71%) expressed
      SMRT, but there was no correlation between expression of corepressors and hormone
      receptor status. All of the primary ovarian cancers and cell lines expressed BRG
      1. Estrogen stimulation of two cell lines expressing ER (SKOV3, OVCA 432)
      elicited low levels of ER-mediated transcription that was not enhanced by BRG-1
      transfection. ICI 182,780 did not induce cell cycle arrest in these cell lines,
      but there was evidence of downregulation of ER, indicating a ligand-receptor
      interaction. However, estrogen did not elicit increased transcription of estrogen
      responsive genes (PR, myc, fos, pS2). CONCLUSION: Inappropriate expression of the
      nuclear corepressors N-CoR and SMRT or the coactivator BRG-1 does not underlie
      the resistance of ovarian cancers to hormonal therapy. Further studies are needed
      to elucidate the mechanisms underlying the inability of ovarian cancers to
      undergo ER-mediated transcription if we hope to understand their resistance to
      hormonal therapy.

PMID- 11336884
TI  - From brainstem to cortex: neurobiologic research provides keys to the riddles,
      mysteries and enigmas of brain dysfunction.

PMID- 11336885
TI  - Spatial enhancement of EEG data by surface Laplacian estimation: the use of
      magnetic resonance imaging-based head models.

PMID- 11336886
TI  - Auditory sensory memory as indicated by mismatch negativity in chronic
      alcoholism.
AB  - OBJECTIVES: A pre-conscious auditory sensory (echoic) memory of about 10 s
      duration can be studied with the event-related brain potential mismatch
      negativity (MMN). Previous work indicates that this memory is preserved in
      abstinent chronic alcoholics for a duration of up to 2 s. The authors' aim was to
      determine the integrity of auditory sensory memory as indexed by MMN in chronic
      alcoholism, when this memory has to be functionally active for a longer period of
      time. METHODS: The presence of MMN for stimuli that differ in duration was tested
      at memory probe intervals (MPIs) of 0.4 and 5.0 s in 17 abstinent chronic
      alcoholic patients and in 17 healthy age-matched control subjects. RESULTS: MMN
      was similar in alcoholics and controls when the MPI was 0.4 s, whereas MMN could
      not be observed in the patients when the MPI was increased to 5.0 s. CONCLUSIONS:
      These results provide evidence of an impairment of auditory sensory memory in
      abstinent chronic alcoholics, whereas the automatic stimulus-change detector
      mechanism, involved in MMN generation, is preserved.

PMID- 11336887
TI  - The vanishing point of the mismatch negativity at sleep onset.
AB  - OBJECTIVE: To determine when the mismatch negativity (MMN) disappears at sleep
      onset, event-related potentials (ERPs) were recorded continuously from
      wakefulness to sleep. METHODS: Ten healthy young students were told to fall
      asleep ignoring the tones presented through a loudspeaker above their head.
      Standard (1000 Hz, P=0.90), high deviant (1200 Hz, P=0.05), and low deviant (1050
      Hz, P=0.05) tones were presented in a quasirandom order with a fixed stimulus
      onset asynchrony of 500 ms. ERP waveforms were obtained separately for 5
      successive stages characterized by typical electroencephalographic (EEG) patterns
      of the sleep onset period. The EEG staging was made manually with very short (5
      s) scoring epochs. RESULTS: The MMN appeared in wakefulness and in the early
      phase of stage 1 sleep (EEG stage II) but disappeared when low-voltage theta
      waves emerged after alpha flattening (EEG stage III). Instead, P240 and N360
      developed particularly for high deviant tones. CONCLUSIONS: Concurrently with the
      disappearance of alpha waves, the automatic change detection system in
      wakefulness seems to stop operating and a different sleep-specific system becomes
      dominant.

PMID- 11336888
TI  - Alpha activity as an index of cortical inhibition during sustained internally
      controlled attention in infants.
AB  - OBJECTIVES: The study examined the suggestion that infant ability to maintain
      attention in anticipatory task and to sustain interference is related to the
      active inhibitory processes in cortical neural networks. METHODS: The extent of
      selective EEG synchronization in the alpha range has been taken as a measure of
      cortical inhibition. EEG was registered in 60 infants aged 8-11 months during:
      (1) attention to an object in the visual field (externally controlled attention);
      (2) anticipation of the person in the peek-a-boo game (internally controlled
      attention). RESULTS: The infants who demonstrated longer periods of anticipatory
      attention had higher absolute spectral amplitude in the broad frequency range
      under both experimental conditions. It was suggested that the effect of 'overall'
      EEG synchronization is related to some stable individual differences in
      psychophysiological traits. To control for the effect of overall EEG
      synchronization the relation between relative alpha amplitudes in 6.4-10 Hz range
      and the duration of internally controlled attention was analyzed. The infants
      with longer compared to shorter anticipatory attention spans had relatively
      higher 6.8 Hz alpha synchronization at posterior parietal sites under this
      experimental condition. CONCLUSIONS: It was suggested that alpha synchronization
      over posterior parietal cortex reflects an active inhibition of certain parietal
      networks involved in maintaining attention to peripheral visual field rather than
      merely an 'idle' state of this cortical area. Such an inhibition appears to allow
      infants to avoid interference of concurrent visual stimulation at the periphery
      of the visual field.

PMID- 11336889
TI  - Test-retest consistency of the event-related desynchronization/event-related
      synchronization of the 4-6, 6-8, 8-10 and 10-12 Hz frequency bands during a
      memory task.
AB  - OBJECTIVE: The aim of this study was to determine the test-retest consistency of
      the event-related desynchronization/event-related synchronization (ERD/ERS)
      method during the performance of an auditory memory task. METHODS: The EEG was
      recorded while 12 subjects performed an auditory memory task on two separate
      occasions (mean test-retest interval 9 days). Differences in the ERD/ERS
      responses between the first and second registrations were examined in 4 EEG
      frequency bands of interest: 4-6, 6-8, 8-10 and 10-12 Hz. RESULTS: We observed
      significant differences in the ERD/ERS responses between the first and second
      registration in all studied frequency bands when examined as a function of time
      and experimental task. The test-retest reliability of the ERD/ERS values was
      highest in the theta frequency range (4-6 and 6-8 Hz), poorer in the 8-10 Hz and
      poorest in the 10-12 Hz alpha frequency range. CONCLUSIONS: The test-retest
      effect was seen in the ERD/ERS responses of all studied frequency bands during an
      auditory memory task.

PMID- 11336890
TI  - Neurobiologic responses to speech in noise in children with learning problems:
      deficits and strategies for improvement.
AB  - OBJECTIVES: Some children with learning problems (LP) experience speech-sound
      perception deficits that worsen in background noise. The first goal was to
      determine whether these impairments are associated with abnormal neurophysiologic
      representation of speech features in noise reflected at brain-stem and cortical
      levels. The second goal was to examine the perceptual and neurophysiological
      benefits provided to an impaired system by acoustic cue enhancements. METHODS:
      Behavioral speech perception measures (just noticeable difference scores),
      auditory brain-stem responses, frequency-following responses and cortical-evoked
      potentials (P1, N1, P1', N1') were studied in a group of LP children and compared
      to responses in normal children. RESULTS: We report abnormalities in the
      fundamental sensory representation of sound at brain-stem and cortical levels in
      the LP children when speech sounds were presented in noise, but not in quiet.
      Specifically, the neurophysiologic responses from these LP children displayed a
      different spectral pattern and lacked precision in the neural representation of
      key stimulus features. Cue enhancement benefited both behavioral and
      neurophysiological responses. CONCLUSIONS: Overall, these findings contribute to
      our understanding of the preconscious biological processes underlying perception
      deficits and may assist in the design of effective intervention strategies.

PMID- 11336891
TI  - Temporal non-linearities of the cochlear amplifier revealed by maximum length
      sequence stimulation.
AB  - OBJECTIVES: The objective of this study was to examine whether temporal non
      linearities of the cochlear amplifier, as reflected by otoacoustic emissions
      (OAEs), exist and are distinct from any recording system non-linearities.
      METHODS: Maximum length sequence stimulation, at various stimulus rates, was used
      to evoke OAEs from normally hearing subjects. Recordings from a 2cc cavity were
      also made. The data were analyzed to obtain the linear response and estimates of
      the slices of the 2nd and 3rd order Volterra kernels. This provided a measure of
      two and 3 click non-linear temporal interactions, respectively. RESULTS: The
      results showed that temporal non-linearities of OAEs do exist, are stable and
      repeatable within individuals and have properties that differ from those shown by
      the conventional linear response. Whilst some of the non-linear response
      properties conformed to the expected pattern, of increasing amplitude with
      increase in stimulus rate, there are some areas in which they show an unpredicted
      complexity. CONCLUSIONS: Whilst system non-linearities could be found, there was
      no difficulty in distinguishing between the physiological and system non-linear
      components. New areas of research and application may result from the use of
      these new OAE responses.

PMID- 11336892
TI  - Separation of mismatch negativity and the N1 wave in the auditory cortex of the
      cat: a topographic study.
AB  - OBJECTIVE: The amplitude distribution of the frequency mismatch negativity (MMN)
      and that of P1 and N1 components were investigated in cats to reveal their
      sources in the auditory areas of the neocortex. METHODS: Pure tone stimuli were
      given in a passive oddball paradigm with different degrees of deviance between
      the standard and deviant tones. Amplitude maps of event-related potential (ERP)
      components were generated from the responses, recorded in awake, freely moving
      animals by a chronically implanted epidural electrode matrix, covering both the
      primary and secondary auditory fields. RESULTS: The P1 and N1 components appeared
      with highest amplitude on the middle ectosylvian gyrus, while the amplitude
      maximum of the MMN was ventral and rostral to them on the AII area. Both the
      latency and the peak amplitude of the MMN depended on the degree of deviance.
      CONCLUSIONS: The MMN is generated in the rostroventral part of the secondary
      auditory area, well separated from the sources of the P1 and N1 components.

PMID- 11336893
TI  - Improved neuromagnetic detection of fetal and neonatal auditory evoked responses.
AB  - OBJECTIVE: To assess the quality of fetal and neonatal auditory evoked responses
      (fAERs and nAERs) obtainable with a low-noise, high-channel count SQUID
      gradiometer in a well-shielded environment. METHODS: Measurement of long-latency
      fAERs was attempted in 19 normal fetuses in 28 sessions at 29-40 weeks'
      gestation, using a 37-channel SQUID gradiometer. Postnatal measurement was
      attempted in 16 neonates in 25 sessions at age 2-6 weeks. RESULTS: Signals of
      amplitude 8 fT or greater were detected in 15 of 28 fetal measurement sessions,
      yielding a higher success rate (54%) than in a previous study of ours. Signals of
      amplitude greater than 25 fT were detected in 23 of 25 (92%) of neonatal
      measurement sessions. The spatial and temporal characteristics of the signals
      were studied in greater detail. Dipole patterns consistent with a source in the
      auditory cortex were observable in nearly all neonates and in many fetuses. The
      dominant component of the nAER was compatible with the P250 seen in neonatal EEG
      recordings; however, the largest component of the fAERs had longer latency and in
      many subjects had opposite polarity. CONCLUSION: A higher success rate, earlier
      detection, and improved characterization of signal morphology and topography were
      demonstrated for fAER recordings.

PMID- 11336894
TI  - Somatosensory evoked potential recovery in myotonic dystrophy.
AB  - OBJECTIVE: To evaluate recovery functions of the sensory cortex using
      somatosensory evoked potentials (SEPs) elicited by paired stimuli of the median
      nerve in patients with myotonic dystrophy (MD). SUBJECTS/METHODS: Twelve MD
      patients were enrolled in the present investigation. Five patients with
      facioscapulohumeral muscular dystrophy (FSH) and 12 healthy volunteers were
      studied as control groups. SEP was recorded from the hand sensory area
      contralateral to the median nerve stimulated at the wrist. Single pulse or paired
      pulse stimuli at various interstimulus intervals (ISIs) (10, 20, 40, 60, 80, 100,
      150, 200 and 300 ms) were given. Recovery functions of N9, N20onset-N20peak, N20
      P25 and P25-N33 components were studied. RESULTS: Conventional SEPs to a single
      stimulus were normal in the latency and amplitude in all the patients. Recovery
      functions of both N9 and N20o-N20p components were normal in the patients. In
      contrast, in MD patients, disinhibited or hyperexcitable recovery pattern was
      observed in recovery curves of the N20-P25 or P25-N33 components, whereas those
      were normal in FSH patients. CONCLUSIONS: Disinhibited cortical excitability (or
      hyperexcitability) is present in the sensory cortex in patients with myotonic
      dystrophy. This may reflect cortical pathology or functional alteration of the
      sensory cortex in MD.

PMID- 11336895
TI  - Hypersomnia in the Prader Willi syndrome: clinical-electrophysiological features
      and underlying factors.
AB  - OBJECTIVE: Excessive daytime sleepiness is a common symptom in Prader Willi
      syndrome (PWs). Sleep disordered breathing (SDB) and narcoleptic traits such as
      REM sleep onsets (SOREMPs) have been reported in these subjects. We evaluated
      nighttime and daytime sleep patterns in patients with PWs in order to clarify the
      nature of their hypersomnia. DESIGN AND METHODS: We performed overnight
      continuous EEG-polysomnographic studies (with breathing monitoring included) in
      14 subjects (6 M,8 F; mean age 17 years, range 8-37) affected by PWs unselected
      for sleep disturbances. Ten patients underwent a Multiple Sleep Latency Test
      (MSLT) the day following the nocturnal sleep studies. Patients assessment was
      completed by means of immunogenetic characterization. RESULTS: Nocturnal
      polysomnographic investigation documented sleep related breathing abnormalities
      such as central apneas, hypopneas or hypoventilation which mainly occurred during
      REM sleep in 8 subjects and did not cause sleep disruption. Only 4 subjects
      presented an increase in the Respiratory Disorder Index (RDI) slightly above the
      normal limits. In 8 subjects out of 10, with and without SDB, the mean daytime
      sleep latency could be considered abnormal according to the Tanner staging of
      pubertal development. Five patients showed at least two SOREMPs at MSLT. Subjects
      with and without SOREMPs had, respectively, a mean age of 18.6 SD 7.9 (4 M, 1 F)
      and 14.5 SD 2.9 (4 F, 1 M). The paternal deletion:uniparental dysomy ratio at
      genotypic characterization was 4:1 and 3.5:1 in subjects with and without
      SOREMPs, respectively. No patient presented DR-15 nor Dq-6. CONCLUSIONS:
      Excessive sleepiness is a frequent disturbance in PWs. Subgroups of PW patients
      show hypersomnolence and SOREMPs. Sleep disordered breathing appears to have a
      limited role in the genesis of hypersomnia which not seems on the other hand
      attributable to the coexistence of narcolepsy phenotype. Hypersomnia in PW
      syndrome is likely to mainly be attributable to a primary hypothalamic
      dysfunction. The potential interacting role of other factors such as subjects
      age, sex and genetic pattern is suggested and deserve further investigation.

PMID- 11336896
TI  - Age and sex effects in the EEG: development of the normal child.
AB  - OBJECTIVES: This study investigated age-related changes and sex differences in
      the EEGs of normal children. METHODS: Forty boys and 40 girls, between the ages
      of 8 and 12 years, participated in this study. The EEG was recorded during an
      eyes-closed resting condition and Fourier transformed to provide estimates for
      total power, absolute and relative power in the delta, theta, alpha and beta
      bands, and for theta/alpha and theta/beta ratios. RESULTS: Absolute delta
      activity decreased with age. Relative delta and theta decreased and alpha and
      beta increased with increasing age. The theta/alpha and theta/beta ratios
      decreased with increasing age. All of these indicated a developmental reduction
      in slow wave activity. Maturational differences were found in the rates of change
      between the midline and the two hemispheres. In the absolute delta and the
      theta/beta ratio, the midline and the two hemispheres became more equipotential
      with age. In the beta band, power increased at a greater rate than in the two
      hemispheres. Sex differences were found, with males having less theta and more
      alpha than females. CONCLUSIONS: These results indicated that maturation occurs
      earlier at the midline than in the two hemispheres. Females were also found to
      have a developmental lag in the EEG compared with males.

PMID- 11336897
TI  - Age and sex effects in the EEG: differences in two subtypes of attention
      deficit/hyperactivity disorder.
AB  - OBJECTIVES: This study investigated age-related changes and sex differences in
      the EEGs of two groups of children with attention-deficit/hyperactivity disorder
      (ADHD) combined type and ADHD predominantly inattentive type, in comparison with
      a control group of normal children. METHODS: Forty boys and forty girls were
      included in each group. The EEG was recorded during an eyes-closed resting
      condition and Fourier transformed to provide estimates for total power, absolute
      and relative power in the delta, theta, alpha and beta bands, and for theta/alpha
      and theta/beta ratios. RESULTS: Total power, relative alpha, and the theta/alpha
      and theta/beta ratios were differentiated between all 3 groups. Sex differences
      between the ADHD subjects and the control group were greater in males than
      females and matured faster in males. With increasing age, the EEG of the ADHD
      inattentive group was found to change at a similar rate to the changes found in
      the normal group, with the differences in power levels remaining constant. In the
      ADHD combined group, the power was found to change at a greater rate than in the
      ADHD inattentive group, with power levels of the two ADHD groups becoming similar
      with age. CONCLUSIONS: These results are supportive of a two-component model of
      ADHD, with the hyperactive/impulsive component maturing with age and the
      inattentive component remaining more stable.

PMID- 11336898
TI  - Mutual information analysis of the EEG in patients with Alzheimer's disease.
AB  - OBJECTIVE: Mutual information provides a measure of both the linear and nonlinear
      statistical dependencies between two time series. Cross-mutual information (CMI)
      is used to quantify the information transmitted from one time series to another,
      while auto mutual information (AMI) in a time series estimates how much on
      average the value of the time series can be predicted from values of the time
      series at preceding points. The aim of this study is to assess information
      transmission between different cortical areas in Alzheimer's disease (AD)
      patients by estimating the average CMI between EEG electrodes. METHODS: We
      recorded the EEG from 16 scale electrodes in 15 AD patients and 15 age-matched
      normal controls, and estimated the local, distant, and interhemispheric CMIs of
      the EEG in both groups. The rate of decrease (with increasing delay) of the AMI
      of the EEG was also measured to evaluate the complexity of the EEG in AD
      patients. RESULTS: The local CMI in AD subjects was lower than that in normal
      controls, especially over frontal and antero-temporal regions. A prominent
      decrease in information transmission between distant electrodes in the right
      hemisphere and between corresponding interhemispheric electrodes was detected in
      the AD patients. In addition, the AMIs throughout the cerebrums of the AD
      patients decreased significantly more slowly with delay than did the AMIs of
      normal controls. CONCLUSIONS: These results are consistent with previous findings
      that suggest the association of EEG abnormalities in AD patients with functional
      impairment of information transmission in long cortico-cortical connections.

PMID- 11336899
TI  - Lateralization of temporal lobe foci: depth versus subdural electrodes.
AB  - OBJECTIVES: Definitive localization of an epileptic focus correlates with a
      favorable outcome following epilepsy surgery. This study was undertaken to
      determine the incremental value of data yielded for surgical decision making when
      using subdural electrodes alone and in addition to depth electrodes for temporal
      lobe epilepsy. METHODS: Standardized placement for intracranial electrodes
      included: (1) longitudinal placement of bilateral temporal lobe depth electrodes;
      (2) bilateral subtemporal subdural strips; and (3) bilateral orbitofrontal
      subdural strips. Sixty-three events were randomly reviewed for: (1) subdural
      electrodes alone; and (2) depth electrodes in conjunction with subdural
      electrodes. RESULTS: Of the 63 seizures, 54 (85.7%) demonstrated congruent
      lateralization to ipsilateral subtemporal subdural strip electrodes (based on
      depth electrode localization) when subdural strip electrodes were utilized alone.
      In 3 of 22 patients, 7 seizures demonstrated 'false localization' on subdural
      electrode analysis alone when compared with depth recording and post-surgical
      outcome. For these 3 patients, retrospective review of neuroimaging demonstrated
      suboptimal ipsilateral placement of subtemporal subdural electrodes with the most
      mesial electrode lateral to the collateral sulcus. Four additional patients had
      suboptimal placement of subtemporal subdural electrodes. Two of these 4 patients
      had congruent localization with subdural electrodes to ipsilateral depth
      electrodes despite suboptimal placement. Subtemporal subdural electrodes
      accurately localized for all seizures from the mesial temporal lobe when the
      mesial electrodes of the subtemporal subdural strip recorded mesial to the
      collateral sulcus from the parahippocampal region. CONCLUSION: We conclude that
      although there are high concordance rates between subdural and depth electrodes,
      localization of seizure onset based on subdural strip electrodes alone may result
      in inaccurate focus identification with potential for possible suboptimal
      treatment of temporal lobe epilepsy. When subtemporal subdural electrodes provide
      recording from the parahippocampal region, there is accurate localization of the
      seizure focus. If suboptimal placement occurs lateral to the collateral sulcus,
      the electroencephalographer cannot make a definitive identification of the
      seizure focus.

PMID- 11336900
TI  - High-resolution EEG: a new realistic geometry spline Laplacian estimation
      technique.
AB  - BACKGROUND: A new realistic geometry (RG) spline Laplacian estimation technique
      has been developed for high-resolution EEG imaging. METHODS: Estimation of the
      parameters associated with the spline Laplacian is formulated by seeking the
      general inverse of a transfer matrix. The number of spline parameters, which need
      to be determined through regularization, is reduced to one in the present
      approach, thus enabling easy implementation of the RG spline Laplacian estimator.
      RESULTS: Computer simulation studies have been conducted to test the feasibility
      of the new approach in a 3-concentric-sphere head model. The new technique has
      also been applied to human visual evoked potential data with a RG head model.
      CONCLUSIONS: The present numerical and experimental results demonstrate the
      feasibility of the new approach and indicate that the RG spline Laplacian can be
      estimated easily from the surface potentials and the scalp geometry.

PMID- 11336901
TI  - Concentric-needle versus macro EMG. II. Detection of neuromuscular disorders.
AB  - OBJECTIVE: Little is known about the relation and sensitivity of macro-EMG (MA
      EMG) compared with concentric-needle EMG (CN-EMG) in the detection of
      neuromuscular disorders. METHODS: CN-EMGs and MA-EMGs were recorded from the
      right brachial biceps muscle of 40 healthy subjects, aged 17-83 years, 20
      patients with neurogenic disorders, aged 25-75 years, and 20 patients with
      myopathy, aged 18-76 years. Motor unit action potentials (MUAPs) were examined.
      RESULTS: In patients with neurogenic disorders CN-MUAP duration, CN-MUAP
      amplitude, percent polyphasia, MA-MUAP amplitude, MA-MUAP area and fibre density
      were significantly increased. In patients with myopathy, only fibre density was
      significantly increased. In patients with neurogenic disorders, the sensitivity
      of CN-EMG was 80%, and that of MA-EMG 85%. In myopathies, the sensitivity was 50%
      for each technique. Pooling the results of both EMG techniques, the sensitivity
      increased to 90% in patients with neurogenic disorders, and to 65% in myogenic
      disease. CONCLUSIONS: MA-EMG has a similar sensitivity in the detection of
      neuromuscular disorders as CN-EMG. Particularly when myopathy is suspected, both
      techniques should be applied if one is unrevealing.

PMID- 11336902
TI  - Sympathetic skin response evoked by respiratory stimulation as a measure of
      sympathetic function.
AB  - OBJECTIVES: To compare respiratory and electrical methods of evoking a
      sympathetic skin response (SSR). METHODS: SSRs evoked by both electrical and
      respiratory stimulation were recorded from the palms of 47 healthy volunteers.
      Expiration and inspiration were used as separate stimuli. The correlation
      coefficients between the amplitude and latency of the SSR from the palm
      electrodes and the various components of heart rate variability were calculated.
      RESULTS: Waveform patterns of the SSRs obtained from electrical stimulation
      showed varied responses to and habituation to this type of stimulation. On the
      other hand, no subjects showed a phase change in SSR waveform patterns between
      the first and last expiratory stimuli. The potentials recorded after expiratory
      stimulation had significantly greater amplitudes than those recorded after
      electrical stimuli. The low frequency component of heart rate variability induced
      by expiratory stimulation was significantly greater than that induced by
      electrical stimulation. The SSR may also correlate strongly with the change of
      respiratory rate since a more rapid pressure change occurs during expiratory
      movement than during inspiratory movements. CONCLUSIONS: The SSR evoked by
      expiratory stimulation is more reliable than either electrical stimulation or
      inspiratory stimulation for determining sympathetic function.

PMID- 11336903
TI  - A comparison between different parameters in F-wave studies.
AB  - Ulnar nerve F-waves were studied in 23 healthy volunteers and 27 diabetic
      patients. Latencies and chronodispersion were analyzed in each group. In the
      diabetic group all the parameters were normal in 14 patients (52%) and in 13
      (48%) at least one parameter was altered. In these patients the most frequently
      altered parameter was the maximum latency (92%), followed by mean latency (85%),
      minimum latency (54%) and chronodispersion (54%). These findings suggest that
      maximum and mean latencies are better parameters to be analyzed in ulnar F-wave
      studies than minimum latency.

PMID- 11336904
TI  - Simulation of EMG in pathological situations.
AB  - OBJECTIVE: A mathematical model for simulation of the EMG from a muscle with its
      motor units is used. The study aims at correlating EMG findings (single-fiber EMG
      and concentric-needle EMG) with various induced morphological changes. METHODS:
      Reinnervation has been simulated by removing motor units randomly followed by a
      complete reinnervation from adjacent surviving motor units. Fibre type grouping
      and grouped atrophy can be seen. Myopathy is simulated by increased fibre
      diameter variation, loss of fibres and muscle fibre splitting. RESULTS AND
      CONCLUSION: The simulation gives quantitative aspects of the importance of each
      of these factors. It indicates the relative sensitivity of various EMG
      parameters. The model can be used both for education and for research.

PMID- 11336905
TI  - Intraoperative monitoring of the bulbocavernosus reflex: the method and its
      problems.
AB  - OBJECTIVES: This study evaluates the method of intraoperative neurophysiological
      monitoring of the bulbocavemosus reflex (BCR) with reference to stimulation and
      detection. METHODS: The study was performed on a group of 65 patients, 53 men and
      12 women, who underwent surgery for lower thoracic and lumbar spinal trauma, with
      no neurological deficit prior to or following surgery. Stimulating electrodes
      were placed on the dorsum of the penis or the clitoris. Single and double stimuli
      were used, as well as trains of 3, 4 and 5 stimuli. Detecting wire electrodes
      were introduced into the perianal region. RESULTS: A single stimulus elicited the
      BCR in 50%, pairs in 75%, trains of 3 in 95%, and trains of 4 and 5 in 100% of
      patients. With placement of the detecting electrodes 2.5 cm deep to the skin, the
      BCR was detected in 13% of hemisphincters in women, and in 81% of hemisphincters
      in men. With controlled intramuscular placement of detecting electrodes, the BCR
      was detected in 97% of hemisphincters in men. With bifocal detection the BCR
      amplitudes were 30-312 mV (median 90), and interside amplitude ratio was 0.05-1
      (median 0.66); with monofocal detection, amplitudes and interside amplitude ratio
      were 30-560 mV (median 200) and 0.15-1 (median 0.86), respectively. CONCLUSIONS:
      A train of 4 electrical stimuli is optimal in eliciting the BCR in anesthetized
      patients. The low rate of elicitability in women was most probably due to
      inefficient stimulation. Detection was improved by controlled intramuscular
      placement of electrodes. Monofocal detection yielded higher BCR amplitudes.
      Interside difference and interindividual variability of the BCR amplitude were
      considerable.

PMID- 11336906
TI  - The shortening reaction of forearm muscles: the influence of central set.
AB  - OBJECTIVE: The EMG of the forearm muscles shortened by an imposed wrist joint
      displacement has been studied at different levels and distribution of background
      muscle activity and with different instructions to the subjects, in order to test
      the hypothesis that the recorded EMG response (shortening reaction, ShoRe) could
      be deliberate in origin. METHODS: Ten normal subjects were examined. A torque
      motor induced 50 degrees wrist extension or flexion at 500 degrees /s. The
      subjects were relaxed or exerted a 10% maximal voluntary contraction. They were
      instructed either not to intervene, or to oppose the displacement, or else to
      assist it. Several trials were repeated at different initial angles. RESULTS: We
      found a short-latency reflex (SR) in the stretched muscle, be it flexor or
      extensor, and a later inconstant ShoRe in the antagonist. ShoRe latency was
      compatible with that of a reaction time (RT), and was not influenced by the
      initial wrist angle. When subjects assisted the movement, the EMG burst in the
      shortening muscle was in every respect a RT; when they opposed the movement, the
      ShoRe disappeared. There was a strict temporal relationship between SR duration
      and ShoRe latency. CONCLUSIONS: We suggest that the brain would deliberately
      trigger the ShoRe on recognizing the displacement direction. The occurrence of
      such activity in the shortened muscle makes the SR to abruptly stop. The temporal
      relationship between the duration of the SR and onset of the ShoRe can be an
      expression of the inhibition on the SR burst by the cortical drive to the
      antagonist muscle being shortened, possibly through the action of spinal
      inhibitory interneurones. The ShoRe would complete the movement momentarily
      braked by the SR and redistribute the muscle tone across antagonists, appropriate
      for the new muscle length.

PMID- 11336907
TI  - Additional somatosensory information does not improve cerebellar adaptation
      during catching.
AB  - OBJECTIVE: People with cerebellar damage are impaired in their ability to adapt
      anticipatory muscle activity during catching. We asked whether prior or on-line
      information about ball weight and drop height could improve the impaired
      adaptation of people with cerebellar damage. METHODS: Cerebellar and control
      subjects caught a series of balls of different weights under two conditions. The
      first condition provided subjects with information about ball weight prior to the
      series of trials. The second condition provided subjects with information about
      ball weight, drop height, and time of ball release during the series of trials.
      Subjects had to maintain their hand within a vertical spatial 'window' during the
      catch. We measured 3-dimensional position and electromyography (EMG) from the
      catching arm. RESULTS: With prior information, controls required a few trials to
      adapt to a new ball weight. Cerebellar subjects were slow, or unable, to adapt.
      With on-line information, controls were able to catch the ball within the window
      immediately, showing that they did not require practice to make this adjustment.
      Cerebellar subjects remained slow or unable to adapt to the changed ball weight
      even with on-line information. CONCLUSIONS: These results suggest that other,
      intact central nervous system structures cannot compensate for the role of the
      cerebellum in generating and adjusting anticipatory muscle activity across
      multiple joints.

PMID- 11336908
TI  - Influence of task-related ipsilateral hand movement on motor cortex excitability.
AB  - OBJECTIVE: The time course of the right motor cortex excitability in relation to
      a task-related voluntary right thumb twitch was studied using sub-threshold
      transcranial magnetic stimulation (TMS) to the right motor cortex. METHODS: Motor
      excitability was studied in 8 adult subjects who made a brief right thumb twitch
      to the predictable omission of every fifth tone in a series of tones 2.5 s apart.
      This paradigm avoided an overt sensory cue, while allowing experimental control
      of TMS timing relative to both movement and the cue to move. Motor excitability
      was characterized by several measures of motor evoked potentials (MEPs) recorded
      from the left thenar eminence in response to TMS over the right scalp with a 9 cm
      coil: probability of eliciting MEPs, incidence of MEPs and amplitude of MEPs.
      RESULTS: All subjects showed suppression of motor excitability immediately
      following a voluntary right thumb twitch (ipsilateral response), and up to 1 s
      after it. However, two distinctly different effects on motor excitability were
      observed before the response: two subjects showed excitation, beginning about 500
      ms before response until 300 ms after it, followed by the post-movement
      suppression; 6 subjects displayed pre-movement suppression, beginning about 600
      ms before the response and persisting for the duration. CONCLUSIONS: The net
      effect of an ipsilateral response on motor cortex can be either inhibitory or
      excitatory, changing with time relative to the response. These findings are
      compatible with two separate processes, inhibitory and excitatory, which interact
      to determine motor excitability ipsilateral to the responding hand.

PMID- 11336909
TI  - Disinhibition of somatosensory and motor cortex in mitochondriopathy without
      myoclonus.
AB  - OBJECTIVE: To test electrophysiologically, if patients with mitochondriopathy but
      without evidence of myocloni have subclinical signs of disinhibition in motor and
      somatosensory cortices. METHODS: Two patients were studied and compared with age
      matched control groups. RESULTS: In both patients, giant somatosensory evoked
      potentials after median nerve stimulation and a reduced intracortical inhibition
      tested by transcranial magnetic stimulation in a paired pulse paradigm indicated
      a dysfunction of inhibitory circuits in the motor as well as the somatosensory
      cortex. In addition, the somatosensory evoked 600 Hz activity recorded by
      magnetoencephalography was abolished. CONCLUSIONS: Patients with
      mitochondriopathy may suffer from a subclinical disturbance of inhibition in the
      sensorimotor cortex. The loss of 600 Hz activity indicates that these high
      frequency oscillations could reflect the activity of inhibitory neurons in the
      somatosensory cortex.

PMID- 11336910
TI  - Event-related desynchronization in reaction time paradigms: a comparison with
      event-related potentials and corticospinal excitability.
AB  - OBJECTIVES: To study cortical activity in different motor tasks, we compared
      event-related desynchronization (ERD) and event-related potentials (ERPs) in
      different reaction time (RT) paradigms with the time course of corticospinal
      excitability. METHODS: Nine right-handed, normal subjects performed right or left
      thumb extensions in simple, choice and go/no go auditory RT paradigms. Eight
      subjects had participated in a previous study evaluating changes in corticospinal
      excitability during the same paradigms. Twenty-nine EEG channels with
      electrooculogram and bilateral EMG monitoring were collected. ERPs and ERD of 10
      and 18-22 Hz bands were obtained with respect to tone administration and EMG
      onset. RESULTS: Trials with movement showed lateralized ERP components,
      corresponding to the motor potential (MP), both in the averages on the tone and
      on EMG. The MP corresponded well in time and location to the rise in
      corticospinal excitability on the moving side observed in the previous study.
      Sensorimotor ERD, followed by event-related synchronization (ERS), was present
      for trials with movements and for the no go. ERD was present contralaterally
      during movement preparation and in no go trials, while it was bilateral during
      motor execution. No go ERD was followed more rapidly by ERS than in trials with
      movement. This finding suggests that in no go trials, there is a brief active
      process in the sensorimotor areas. ERD and ERS do not correspond, respectively,
      in time and location to increases and decreases in corticospinal excitability. In
      fact, ERD is bilateral during movement execution, when corticospinal inhibition
      of the side at rest is observed. Contralateral no go ERS occurs later than
      corticospinal inhibition, which is bilateral. CONCLUSIONS: These findings may
      suggest that ERD is compatible with both corticospinal activation and inhibition,
      ERS indicating the removal of either, resulting in cortical idling.

PMID- 11336911
TI  - Mechanisms influencing stimulus-response properties of the human corticospinal
      system.
AB  - BACKGROUND: Stimulus-response (S-R) properties of the corticospinal system in
      humans depend on the interactions that take place at different sites along the
      corticospinal pathway. The mechanisms influencing stimulus-response curves
      elicited by transcranial magnetic stimulation (TMS) and their operation site
      along the human neuraxis are poorly understood. In this study, we investigated
      the effects of CNS-active drugs with distinct mechanisms of action on S-R curves.
      Effects of each of these drugs on S-R curves would point to the involvement of
      specific mechanisms. Additionally, relative sensitivity of S-R curves compared
      with other measures of corticospinal excitability was studied. METHODS: We
      studied the effects of lorazepam, which is a positive allosteric modulator of
      GABA(A) receptors; lamotrigine, an inhibitor of voltage-gated Na(+) and Ca(2+)
      channels; and D-amphetamine, an indirect agonist of the dopaminergic-adrenergic
      system on S-R curves, motor thresholds (MT), and intracortical inhibition (ICI)
      and facilitation (ICF) with a double-pulse technique. Maximum peripheral M
      responses and F waves were investigated as measures of the total alpha-motoneuron
      pool and its excitability. RESULTS: F and M waves were unaffected by either the
      drugs or placebo. S-R curves were significantly depressed by lorazepam and
      lamotrigine without changes in ICI and ICF. Both S-R curves and ICF were enhanced
      by D-amphetamine. MT increased only with lamotrigine. CONCLUSIONS: S-R curves
      were influenced by changes in the GABAergic and monoaminergic system and Na(+)
      and Ca(2+) channel properties. Our results indicate that, out of different
      parameters of motor system excitability, S-R curves were the most sensitive.

PMID- 11336912
TI  - The triple stimulation technique to study central motor conduction to the lower
      limbs.
AB  - OBJECTIVE: To quantify the percentage of motor units of a foot muscle that can be
      activated by transcranial magnetic stimulation (TMS) in normal subjects and
      patients. METHODS: We adapted the recently described triple stimulation technique
      (TST) for recordings from abductor hallucis (AH). Conventional motor evoked
      potentials (MEPs) of this muscle are usually small and variable in shape, because
      of an important temporal desynchronization of the TMS induced spinal motor neuron
      discharges. The TST allows 'resynchronization' of these discharges and thereby a
      quantification of the proportion of motor units activated by TMS. The lower limb
      (LL-) TST was applied to 33 sides of 18 normal subjects and 51 sides of 46
      patients with multiple sclerosis, amyotrophic lateral sclerosis, or spinal cord
      disorders. RESULTS: In healthy subjects, the LL-TST demonstrated that TMS
      achieves activation of virtually all motor neurons supplying the AH. In 33 of 51
      patient sides, abnormal LL-TST responses suggested corticospinal conduction
      failures of various degrees. The LL-TST was 2.54 times more sensitive to detect
      central conduction failures than the conventional LL-MEPs. Combining the LL-TST
      with TST of the upper limbs further increased the sensitivity to detect a
      conduction failure by 1.50 times. CONCLUSION: The LL-TST markedly improves the
      examination of corticospinal pathways.

PMID- 11336914
TI  - Local application of growth factors (insulin-like growth factor-1 and
      transforming growth factor-beta1) from a biodegradable poly(D,L-lactide) coating
      of osteosynthetic implants accelerates fracture healing in rats.
AB  - In vitro and in vivo studies have demonstrated an osteoinductive effect of growth
      factors such as insulin-like growth factor-1 (IGF-1) and transforming growth
      factor-beta1 (TGF-beta1). However, for therapeutic use in fracture treatment,
      questions remain with regard to the local application of these proteins. A
      controlled, local release of growth factors from a biodegradable polylactide
      coating of osteosynthetic implants may have a stimulating effect on fracture
      healing. Such implants could stabilize the fracture and their bioactive surface
      could function simultaneously as a local drug-delivery system. Previous studies
      have demonstrated the high mechanical stability of an approximately 10-14-microm
      thick poly(D,L-lactide) (PDLLA) coating on metallic implants, which can even
      withstand the process of intramedullary insertion. Following an initial peak, 80%
      of incorporated growth factors IGF-1 and TGF-beta1 were continuously released
      within 42 days. The effect of locally applied IGF-1 and TGF-beta1 from a
      biodegradable PDLLA coating of intramedullary implants on fracture healing was
      investigated in a rat model. Midshaft fractures of the right tibia of 5-month-old
      female Sprague-Dawley rats (n = 127) were stabilized with coated vs. uncoated
      titanium Kirschner wires. X-ray examinations and blood analyses were performed,
      and body weight and body temperature measurements were taken throughout the
      experimental period. After 28 and 42 days, respectively, tibiae were dissected
      for mechanical torsional testing and histomorphometrical analyses. X-rays
      demonstrated an almost completely consolidated fracture, biomechanical testing
      showed a significantly higher maximum load and torsional stiffness, and
      histological and histomorphometric analyses demonstrated progressed remodeling
      after 28 and 42 days in the group treated with growth factors as compared with
      controls. Interestingly, the PDLLA coating itself revealed a positive effect on
      fracture healing even without incorporated growth factors. No systemic changes of
      serum parameters, including IGF-1 and IGF binding proteins, and no differences in
      body weight and body temperature were observed within and between groups. These
      findings suggest that the local application of growth factors from a
      biodegradable PDLLA coating of osteosynthetic implants accelerates fracture
      healing significantly without systemic side effects.

PMID- 11336915
TI  - Individual osteoblasts in the developing calvaria express different gene
      repertoires.
AB  - Several studies in vitro and a few in vivo have suggested that mature osteoblasts
      heterogeneously express osteoblast markers. In one recent study of the
      osteoblasts associated with bone nodules formed in vitro in rat calvaria cell
      populations, extensive diversity was documented in the overall gene repertoires
      expressed. To address whether comparable heterogeneity is evident in vivo, we
      investigated the expression of nine osteoblast lineage markers by both in situ
      hybridization and immunohistochemistry. At 21 days of fetal rat development, the
      calvaria is a rapidly growing bone with distinct maturational zones that are
      readily observed in coronal sections; that is, an osteogenic front emerging at
      sagittal and coronal sutures is adjacent to areas of growing trabeculae of bone,
      followed by more mature areas of remodeling bone. Based on expression patterns,
      markers can be divided into two categories. One category comprises markers that
      are globally expressed by all osteoblasts irrespective of their position in the
      calvaria. Of those tested, only two, alkaline phosphatase and the pth/pthrp
      receptor, fit into this category. All other markers analyzed, including
      transcription factors (c-fos and msx-2), matrix molecules (bone sialoprotein,
      osteopontin, and osteocalcin), and a hormone (pthrp), were differentially
      expressed only in subpopulations of osteoblasts, based on cell maturational
      status, environment (ectocranial vs. endocranial surfaces), and microenvironment
      (adjacent osteoblasts). Preosteoblasts and osteocytes in different regions of the
      calvaria also expressed different subsets of the lineage markers. Mechanisms
      responsible for generating differential gene expression profiles appear to be
      both transcriptional and posttranscriptional. These results indicate that
      postproliferative, morphologically indistinguishable osteoblasts are not a
      homogeneous class of cells, but instead are molecularly diverse. The present
      results also raise the possibility that lineage progression and/or maintenance of
      the differentiated state may be adaptable in the calvaria.

PMID- 11336916
TI  - Gap-junctional communication is required for the maturation process of
      osteoblastic cells in culture.
AB  - Osteoblastic cells in long-term culture undergo a phenotypic maturation process
      leading to extracellular matrix (ECM) production and bone nodule (BN) formation.
      Cell-to-cell communication via gap junctions (GJC) can be detected between
      osteoblastic cells within 24 h of plating. We evaluated, in long-term cultures of
      osteoblastic cells, the effect of inhibiting GJC on the phenotypic maturation
      process and the expression of specific genes associated with this process. MC3T3
      E1 cells were plated, and, after 24 h (day 0), cells were exposed to 18-alpha
      glycyrrhetinic acid (AGA), a nontoxic reversible inhibitor of GJC. GJC, alkaline
      phosphatase (AP) activity, BN formation, and the relative level of transcripts
      encoding osteocalcin (OC), bone sialoprotein (bSP), osteopontin (OP), collagen
      alpha1 type I (alpha1ICol), and elongation factor-1a (EF1a) were evaluated on day
      0 and every 4-7 days thereafter through day 30. GJC was assessed by fluorescent
      dye transfer. Gene expression was analyzed by northern blot and semiquantitative
      reverse transcription-polymerase chain reaction. GJC was detectable at day 0 and
      increased with time in culture. AGA (100 micromol/L) strongly inhibited GJC at
      all timepoints tested. Moreover, AGA-exposed cells showed a dose-dependent
      decrease in AP activity and a delay in the appearance of BN. This delayed
      phenotypic expression coincided with an inhibitory effect on the expression of
      the osteoblast-specific genes OC and bSP. Expression of alpha1ICol mRNA was also
      affected, but to a lesser extent, whereas OP and EF1a were not affected. Similar
      results were obtained with oleamide, an additional reversible inhibitor of GJC.
      In contrast, cells exposed to either vehicle or 100 micromol/L glycyrrhizic acid
      (a noninhibitory glycoside of 18-beta-glycyrrhetinic acid) were indistinguishable
      from untreated cells for all parameters evaluated. We conclude that GJC
      inhibition interferes with the maturation process of osteoblastic cells in
      culture, possibly by affecting signals regulating the expression of genes
      involved in the maturation/differentiation of the osteoblastic phenotype.

PMID- 11336917
TI  - Osteoprotegerin inhibits osteoclast formation and bone resorbing activity in
      giant cell tumors of bone.
AB  - Osteolysis is a common complication of tumors that arise in, or metastasize to,
      bone. The recent discovery of key regulators of osteoclast formation and
      activity, including receptor activator of nuclear factor of kappaB ligand
      (RANKL), RANK, and osteoprotegerin (OPG), may facilitate new treatment regimes
      for certain tumors associated with excessive bone loss. We recently showed that
      the stromal cells of osteolytic giant cell tumors (GCT) of bone express high
      levels of mRNA encoding RANKL, relative to mRNA for the RANKL antagonist, OPG,
      compared with the expression patterns of other lytic and nonlytic bone tumors. In
      this study, we found that expression of RANKL and OPG mRNA continued by the
      stromal element of these tumors in a constitutive manner for at least 9 days in
      the absence of giant cells. Immunostaining of unfractionated GCT cultured in
      vitro revealed punctate cytoplasmic/membranous staining for RANKL and both
      cytoplasmic and extracellular matrix staining for OPG in stromal cells. Giant
      cells (osteoclasts) were negative for RANKL staining, but stained brightly for
      cytoplasmic OPG protein. We also investigated the functional relevance of these
      molecules for GCT osteolysis by adding recombinant OPG and RANKL to cultured GCT
      cells. We found that OPG treatment potently and dose-dependently inhibited
      resorption of bone slices by GCT, and could also inhibit the formation of
      multinucleated osteoclasts from precursors within the GCT. These effects of OPG
      were reversed by stoichiometric concentrations of exogenous RANKL. These data
      indicate that both the processes of osteoclast formation and activation in GCT
      are promoted by RANKL. Therefore, GCT represent a paradigm for the direct
      stimulation of osteoclast formation and activity by tumor stromal cells, in
      contrast to the mechanisms described for osteolytic breast tumors and multiple
      myeloma. The demonstration of these relationships is important in developing
      approaches to limit tumor-induced osteolysis.

PMID- 11336918
TI  - Effect of interleukin-17 on nitric oxide production and osteoclastic bone
      resorption: is there dependency on nuclear factor-kappaB and receptor activator
      of nuclear factor kappaB (RANK)/RANK ligand signaling?
AB  - Interleukin-17 (IL-17) is a proinflammatory cytokine produced exclusively by
      activated memory T cells and has recently been found to stimulate osteoclastic
      resorption. Like other proinflammatory cytokines, IL-17 may affect osteoclastic
      bone resorption indirectly via osteoblasts, possibly by mechanisms previously
      reported for chondrocytes that respond in very similarly to osteoblasts. As in
      chondrocytes, but only in combination with tumor necrosis factor-alpha (TNF
      alpha), IL-17 induced nitric oxide (NO) production in osteoblastic cells and
      fetal mouse metatarsals by a nuclear factor-kappaB (NF-kappaB)-dependent
      mechanism. This effect was associated with elevated mRNA levels of the NF-kappaB
      isoforms RelA and p50. In fetal mouse metatarsals, IL-17 stimulated osteoclastic
      bone resorption only in combination with TNF-alpha. The pathway by which the
      cytokine combination exerts this effect was examined using inhibitors of NO
      synthesis and NF-kappaB activation. Although both inhibitors used abolished NO
      production, they did not prevent the stimulatory effect of the cytokine
      combination on osteoclastic resorption. In contrast, the inhibitors slightly
      increased osteoclastic resorption, suggesting a suppressive rather than
      stimulatory effect of NO on cytokine-induced bone resorption. In addition, we
      showed that IL-17 + TNF-alpha stimulated osteoclastic resorption independent of
      NF-kappaB signaling. To further examine the pathway by which osteoclastic
      resorption was stimulated, we used osteoprotegerin, a specific inhibitor of the
      receptor activator of NF-kappaB (RANK)/receptor activator of the NF-kappaB ligand
      (RANKL) pathway. Osteoprotegerin partially inhibited IL-17 + TNF-alpha-stimulated
      osteoclastic resorption only at the high concentration of 1000 ng/mL, whereas it
      completely blocked parathyroid hormone-related peptide-stimulated resorption at
      300 ng/mL. In conclusion, IL-17 stimulated NO production by an NF-kappaB
      dependent pathway in osteoblastic cells and fetal mouse metatarsals only in
      combination with TNF-alpha. Neither NO production nor NF-kappaB signaling, and
      only partly the RANK/RANKL pathway, were involved in the stimulatory effect of
      the cytokine combination on osteoblastic bone resorption in these long bones,
      suggesting the existence of other pathways by which osteoclastic resorption can
      be stimulated.

PMID- 11336919
TI  - Homocysteine decreases chondrocyte-mediated matrix mineralization in
      differentiating chick limb-bud mesenchymal cell micro-mass cultures.
AB  - The differentiating chick limb-bud mesenchymal cell micro-mass culture system has
      been used as a model for monitoring the effects of matrix modification on cell
      mediated calcification. In this study, we show that treating these micro-mass
      cultures with homocysteine (Hcys) impairs cartilage calcification. Cultures were
      treated from day 2 to day 7 with two nonphysiological concentrations of Hcys
      equivalent to 100x and 1000x avian serum levels (0.36 and 3.6 mmol/L), and from
      days 9-13 with one tenth the concentration. Mineralization assays were done at
      days 16, 19, and 21, and matrix and cell properties were examined between days 5
      and 21. Mineral accretion, based on differential (45)Ca uptake (mineralizing
      minus control cultures), was significantly reduced in the high-Hcys-concentration
      group, and slightly reduced in the low-Hcys-concentration group. Electron
      microscopy at culture day 21 showed that the collagen matrix was less abundant
      and its banding pattern less obvious in the Hcys-treated groups than in the
      untreated cultures. Pyridinoline (Pyr) and deoxypyridinoline (d-Pyr) contents
      were not detectable in day 21 cultures with either 0.36 or 3.6 mmol/L
      homocysteine, whereas values in mineralizing and nonmineralizing controls ranged
      from 0.06 to 0.08 and 0.03 to 0.06 (moles/mole collagen) for Pyr and d-Pyr,
      respectively. Fourier transform infrared (FTIR) imaging also indicated a
      decreased content of pyridinoline cross-links. Hcys caused other matrix changes
      as well. Whereas at culture day 5 there was no significant difference in the
      number of chondrocyte nodules formed, by day 11 the proteoglycan content
      (measured by Alcian blue dye binding at 595 nm) was significantly reduced in both
      mineralizing and control cultures in the high- and low-Hcys groups. In contrast,
      there were no detectable differences in type X collagen and alkaline phosphatase
      staining in the mineralizing cultures with or without Hcys supplements. Because
      vital dye stains and electron microscopy studies indicated that cells in the
      control and experimental groups did not differ in terms of viability, the
      observed differences cannot be attributed to toxicity. Thus, Hcys treatment,
      which causes matrix disorganization, decreases the ability of the matrix to
      support mineralization.

PMID- 11336920
TI  - Altered mRNA level of matrix metalloproteinase-13 in MH7A synovial cells under
      mechanical loading and unloading.
AB  - In an effort to elucidate the interplay between mechanical load and proteolytic
      gene expression in arthritic tissue degradation, we investigated cellular
      morphology and mRNA levels of matrix metalloproteinase-13 (MMP-13) genes under
      mechanical stress in human MH7A synovial cells. The cells were isolated from the
      knee joint of a rheumatoid arthritis patient. Using a reverse transcription
      polymerase chain reaction procedure, we found that loading by an oscillatory
      shaker transiently decreased the level of MMP-13 mRNA and unloading by a
      clinostat increased its mRNA level. The unloaded cells appeared to be rounded and
      displayed a poorly developed track of peripheral fibers, whereas the cells under
      loading tended to align to the shear flow and were elongated. We also found that
      altering the oscillatory direction of mechanical loads contributed to a further
      reduction in mRNA expression of MMP-13. Our results demonstrate the role of
      mechanical loading and unloading in the transcriptional regulation of MMP-13 in
      synovial cells, and suggest the potential value of physical therapy for arthritic
      joints.

PMID- 11336921
TI  - Gene and protein expression of brain-derived neurotrophic factor and TrkB in bone
      and cartilage.
AB  - Gene and protein expressions of brain-derived neurotrophic factor (BDNF) and
      TrkB, the high-affinity receptor of BDNF, were investigated in the femur and
      mandibular condyle of rats by in situ hybridization and immunohistochemistry.
      BDNF and TrkB mRNA showed overlapped expression in chondrocytes in proliferating
      and mature zones of the epiphyseal growth plate cartilage and mandibular condylar
      cartilage, and in cuboidal-shaped active osteoblasts at the site of endochondral
      and intramembranous ossification and in trabecular bone. Expression of BDNF
      protein also showed a similar localization. The present study suggests that BDNF
      may participate in regulating the development and remodeling of bony tissue in
      the developing rat.

PMID- 11336922
TI  - Androgen-accelerated bone maturation in mice is not attenuated by Faslodex, an
      estrogen receptor blocker.
AB  - Androgens accelerate bone maturation, but it is unclear to what extent this
      process may be mediated by estrogens derived from aromatization of androgens. In
      this study, we investigated whether an estrogen-blocking agent, Faslodex (ICI
      182,780), can attenuate testosterone-accelerated skeletal maturation in immature
      mice. On days of life 2-8, mouse pups received either testosterone propionate (50
      microg/100 g body weight), Faslodex (100 microg/100 g body weight), a combination
      of Faslodex + testosterone, or vehicle alone. Skeletal maturation was assessed in
      the forepaw and the lumbar spine. Testosterone caused acceleration of bone
      maturation (p < 0.05, compared with vehicle), predominantly of axial bones.
      Faslodex, however, failed to block the effect of testosterone, such that the mice
      receiving Faslodex + testosterone had skeletal maturation scores similar to those
      treated with testosterone alone. These results suggest that androgens have the
      capacity to stimulate bone maturation directly, probably via their own receptors.

PMID- 11336923
TI  - Maintenance of vertebral body bone mass and strength created by human parathyroid
      hormone treatment in ovariectomized rats.
AB  - The purpose of this cross-sectional study was to evaluate the effects of human
      parathyroid hormone (1-84) (hPTH) followed by maintenance administration of
      17beta-estradiol (E2), risedronate (Ris), or a reduced dose of hPTH (LowPTH) on
      vertebral body bone mineral density (BMD) and bone strength in ovariectomized
      (ovx) rats. Eight groups of ovx (219 rats) and one group of intact female rats
      (48 rats) were left untreated for 11 weeks (age 3.5 months at the beginning). For
      the following 12 weeks, four ovx groups received subcutaneous injections of hPTH
      (75 microg/kg per day, 3 days/week) and four groups received vehicle. Treatments
      were then changed to: E2 (10 microg/kg per day, 2 days/week); Ris (3 microg/kg
      per day, 3 days/week); LowPTH (25 microg/kg per day, 3 days/week); or vehicle for
      36 weeks. Bone tissue was collected at weeks -11 (baseline), 0 (ovx effect), 12
      (hPTH effect), 24, 36, and 48 (maintenance effect). The endpoints were vertebral
      body BMD, ultimate stress (Ultstr), and moduli of elasticity from compression
      tests (ModM), and from ultrasound tests (ModUS). Ovariectomy resulted in lower
      BMD (p < 0.001). The hPTH treatment for 12 weeks restored BMD to the level of
      intact rats. Ultstr and ModUS followed a similar pattern, but the ovx-induced
      Ultstr was not significant (p = 0.073, ModUS: p = 0.003), nor was the hPTH
      induced increase in ModUS (p = 0.131, Ultstr: p = 0.02). After hPTH withdrawal,
      BMD, Ultstr, and ModUS levels were not different from levels in ovx animals. In
      Ris-treated rats pretreated with hPTH, BMD (weeks 24 and 48, p < 0.002) and ModUS
      (week 24, p = 0.018) values were greater than in ovx animals. In LowPTH-treated
      rats pretreated with hPTH, BMD (weeks 24 and 48, p < 0.001) and Ultstr (week 48,
      p = 0.005) were greater than in ovx animals. In E(2)-treated rats pretreated with
      hPTH, BMD was greater than in ovx rats at week 24 (p = 0.009), but did not differ
      at weeks 36-48. Neither Ultstr nor ModUS in E(2)-treated rats differed
      significantly from ovx rats at any timepoint. Of the agents and dosing regimens
      used, we conclude that the hPTH-related vertebral bone mass gain in ovx rats can
      be maintained for up to 36 weeks with risedronate and low-dose hPTH treatment.
      Bone strength is maintained by treatment with low-dose hPTH, but only partially
      maintained with risedronate.

PMID- 11336924
TI  - A metaphyseal defect model of the femur for studies of murine bone healing.
AB  - A bone defect model was developed in the distal metaphysis of the femur for
      studies on bone healing in the mouse. The circular defect involving 20% of the
      bone circumference resulted in a 34% reduction in the bending moment compared to
      intact bone. The healing process was followed using histomorphometry, peripheral
      quantitative computed tomography (pQCT), biomechanical testing, and molecular
      biological analyses. Histologically, healing of the defect was characterized by
      filling of the medullary cavity with trabecular new bone during the first week of
      healing, and by closing of the cortical window by 6 weeks. Small areas of
      periosteal chondrogenesis were frequently observed during defect healing. In
      pQCT, bone mineral content (BMC) of the defect area approached that of intact
      control bone already by 3 weeks, reflecting the production of trabecular bone.
      Similarly, the bending strength and stiffness of the healing femur reached the
      level of intact control femur already at 3 weeks. Bone formation and remodeling
      was followed by Northern analyses, which demonstrated elevated mRNA levels for
      bone components (type I collagen and osteocalcin), and for osteoclastic enzymes
      (cathepsin K, matrix metalloproteinase-9, and tartrate-resistant acid
      phosphatase) throughout the healing period. Finally, the applicability of the
      defect model for gene therapy experiments was tested using adenovirus-mediated
      transfer of the LacZ reporter gene. Both histochemistry and mRNA analyses
      demonstrated that the gene was expressed in the repair tissue with the highest
      expression during the first week of healing. The present model thus provides a
      standardized environment for studies on induction and remodeling of trabecular
      new bone in normal and genetically engineered mice.

PMID- 11336926
TI  - Targeting of hormone replacement therapy immediately after menopause.
AB  - The aim of this study was to model the effect of short (3-year) treatments with
      hormone replacement therapy (HRT) at the time of menopause on the risk of
      osteoporotic fracture, and to assess the impact of strategies to target high-risk
      individuals. From the relationship between bone mineral density (BMD) and
      fracture risk, treatment that increased bone mineral density at the hip by 6%
      over untreated women would save 35 vertebral, 62 hip, 13 proximal humeral, and 16
      forearm fractures per 1000 women. The number needed to treat (NNT) to prevent one
      of these fractures was 8. The NNT fell modestly by targeting HRT to women with
      low bone mass or osteoporosis (NNT 6 and 5, respectively). The gains in fractures
      saved from targeting women with low bone mass or osteoporosis were offset by the
      requirement for assessment by BMD. Changes in the assumptions about the efficacy
      of HRT had a modest impact on fractures saved compared with the effect of
      changing assumptions concerning the offset of effect when treatment was stopped.
      We conclude that comparatively short courses of HRT might be effectively offered
      to all suitable women at menopause provided that the effects on bone persist when
      treatment is stopped.

PMID- 11336925
TI  - Phosphate wasting in oncogenic osteomalacia: PHEX is normal and the tumor-derived
      factor has unique properties.
AB  - Oncogenic osteomalacia (OOM) is characterized by renal phosphate wasting and
      abnormal metabolism of vitamin D, somewhat similar to the phenotype of X-linked
      hypophosphatemic rickets (HYP). DNA from OOM tumor cells was analyzed for
      mutations in the PHEX gene, which is mutated in HYP. Screening for mutations by
      single-strand conformation polymorphism analysis and subsequent sequencing of all
      the exons revealed no mutations. Conditioned media from long-term cultures of OOM
      tumor cells were used to further characterize the physical properties of the
      phosphate-regulating factor and its mechanism of action. Inhibition of OK 3B2
      cell renal phosphate transport by conditioned media was dose-dependent and
      maximal after 20 h. This time course differed from that of parathyroid hormone
      (PTH). The bioactivity was stable to mild acid and alkali treatment and freeze
      drying and was retained in the aqueous phase following organic solvent
      extraction. The activity was not suppressed by heat or by treatment with trypsin
      but was suppressed by the protease papain and had an apparent molecular weight of
      < 5000. No change was detected in the expression of type II sodium/phosphate
      cotransporter (NaPi) mRNA in OK 3B2 cells in response to conditioned media,
      unlike the reduction seen in Hyp mice. In the presence of colchicine or
      cytochalasin D, the inhibitory response to conditioned media was reduced, similar
      to the effect of these agents on the response to PTH. Cycloheximide also
      suppressed the inhibitory response of conditioned media, but not the response to
      PTH. These studies indicate that mutations in the PHEX gene are unlikely to be
      responsible for OOM and suggest that the tumor-derived factor that inhibits
      phosphate uptake is a small protein that does not downregulate type II NaPi mRNA,
      and requires an intact cytoskeleton and protein synthesis for activity.

PMID- 11336927
TI  - Incorporation and distribution of strontium in bone.
AB  - The distribution and incorporation of strontium into bone has been examined in
      rats, monkeys, and humans after oral administration of strontium (either
      strontium chloride or strontium ranelate). After repeated administration for a
      sufficient period of time (at least 4 weeks in rats), strontium incorporation
      into bone reaches a plateau level. This plateau appears to be lower in females
      than in males due to a difference in the absorption process. Steady-state plasma
      strontium levels are reached more rapidly than in bones, and within 10 days in
      the rat. The strontium levels in bone vary according to the anatomical site.
      However, strontium levels at different skeletal sites are strongly correlated,
      and the strontium content of the lumbar vertebra may be estimated from iliac
      crest bone biopsies in monkeys. The strontium levels in bone also vary according
      to the bone structure and higher amounts of strontium are found in cancellous
      bone than in cortical bone. Furthermore, at the crystal level, higher
      concentrations of strontium are observed in newly formed bone than in old bone.
      After withdrawal of treatment, the bone strontium content rapidly decreases in
      monkeys. The relatively high clearance rate of strontium from bone can be
      explained by the mechanisms of its incorporation. Strontium is mainly
      incorporated by exchange onto the crystal surface. In new bone, only a few
      strontium atoms may be incorporated into the crystal by ionic substitution of
      calcium. After treatment withdrawal, strontium exchanged onto the crystal is
      rapidly eliminated, which leads to a rapid decrease in total bone strontium
      levels. In summary, incorporation of strontium into bone, mainly by exchange onto
      the crystal surface, is dependent on the duration of treatment, dose, gender, and
      skeletal site. Nevertheless, bone strontium content is highly correlated with
      plasma strontium levels and, in bone, between the different skeletal sites.

PMID- 11336928
TI  - Low bone mineral density in the femoral neck of medieval women: a result of
      multiparity?
AB  - An archaeological investigation of a medieval cemetery gave us the opportunity to
      investigate 49 Danish skeletons dating from 1000 to 1250 A.D. and to compare them
      with 298 contemporary Danes (aged 19-79 years) and assess the millennial trend in
      bone mineral density (BMD) in populations considered genetically closely related.
      BMD and bone mineral apparent density (BMAD) of the femoral neck were measured by
      dual-energy X-ray absorptiometry (DEXA) and transformed into z scores.
      BMD(zscore) was significantly lower in medieval women (-0.54 +/- 0.25, p = 0.04),
      whereas BMD(zscore) in medieval men was significantly higher (0.55 +/- 0.22, p =
      0.02). In medieval women, BMD(zscore) tended to increase with age (r = 0.42, p =
      0.07), whereas no change was seen in men (r = 0.19, not significant [n.s.]).
      Also, BMAD(zscore) was significantly elevated in medieval men (1.00 +/- 0.28, p <
      0.01), but in medieval women no difference was found (-0.28 +/- 0.21, n.s.).
      However, the correlation between BMAD(zscore) and age was significant in the
      medieval women where it increased with advancing age (r = 0.49, p = 0.03). In
      conclusion, medieval women had lower BMD when compared with contemporary women,
      but this relationship was reversed in women who survived to older ages. In
      contrast, medieval men had significantly higher BMD as compared with contemporary
      men at all ages. The observed lower BMD in medieval women can be explained by the
      well-known selective mortality among the younger women. A high birth rate and
      prolonged periods of lactation are the main reasons for the observed increased
      mortality, and therefore can also very likely explain the associated low BMD. The
      increase in the incidence of osteoporosis in modern elderly women could possibly,
      or partially, be explained by the survival of women who would have died
      prematurely had they lived in earlier centuries.

PMID- 11336929
TI  - Verteporfin therapy of subfoveal choroidal neovascularization in age-related
      macular degeneration: two-year results of a randomized clinical trial including
      lesions with occult with no classic choroidal neovascularization--verteporfin in
      photodynamic therapy report 2.
AB  - PURPOSE: To determine if photodynamic therapy with verteporfin (Visudyne;
      Novartis AG, Bulach, Switzerland), termed verteporfin therapy, can safely reduce
      the risk of vision loss compared with a placebo (with sham treatment) in patients
      with subfoveal choroidal neovascularization caused by age-related macular
      degeneration who were identified with a lesion composed of occult with no classic
      choroidal neovascularization, or with presumed early onset classic choroidal
      neovascularization with good visual acuity letter score. METHODS: This was a
      double-masked, placebo-controlled (sham treatment), randomized, multicenter
      clinical trial involving 28 ophthalmology practices in Europe and North America.
      The study population was patients with age-related macular degeneration, with
      subfoveal choroidal neovascularization lesions measuring no greater than 5400
      microm in greatest linear dimension with either 1) occult with no classic
      choroidal neovascularization, best-corrected visual acuity score of at least 50
      (Snellen equivalent approximately 20/100), and evidence of hemorrhage or recent
      disease progression; or 2) evidence of classic choroidal neovascularization with
      a best-corrected visual acuity score of at least 70 (better than a Snellen
      equivalent of approximately 20/40); assigned randomly (2:1) to verteporfin
      therapy or placebo therapy. Verteporfin (6 mg per square meter of body surface
      area) or placebo (5% dextrose in water) was administered by means of intravenous
      infusion of 30 ml over 10 minutes. Fifteen minutes after the start of the
      infusion, a laser light at 689 nm delivered 50 J/cm(2) by application of an
      intensity of 600 mW/cm(2) over 83 seconds using a spot size with a diameter 1000
      microm larger than the greatest linear dimension of the choroidal
      neovascularization lesion on the retina. At follow-up examinations every 3
      months, retreatment with the same regimen was applied if angiography showed
      fluorescein leakage. The main outcome measure was at least moderate vision loss,
      that is, a loss of at least 15 letters (approximately 3 lines), adhering to an
      intent-to-treat analysis with the last observation carried forward to impute for
      missing data. RESULTS: Two hundred ten (93%) and 193 (86%) of the 225 patients in
      the verteporfin group compared with 104 (91%) and 99 (87%) of the 114 patients in
      the placebo group completed the month 12 and 24 examinations, respectively. On
      average, verteporfin-treated patients received five treatments over the 24 months
      of follow-up. The primary outcome was similar for the verteporfin-treated and the
      placebo-treated eyes through the month 12 examination, although a number of
      secondary visual and angiographic outcomes significantly favored the verteporfin
      treated group. Between the month 12 and 24 examinations, the treatment benefit
      grew so that by the month 24 examination, the verteporfin-treated eyes were less
      likely to have moderate or severe vision loss. Of the 225 verteporfin-treated
      patients, 121 (54%) compared with 76 (67%) of 114 placebo-treated patients lost
      at least 15 letters (P =.023). Likewise, 67 of the verteporfin-treated patients
      (30%) compared with 54 of the placebo-treated patients (47%) lost at least 30
      letters (P =.001). Statistically significant results favoring verteporfin therapy
      at the month 24 examination were consistent between the total population and the
      subgroup of patients with a baseline lesion composition identified as occult
      choroidal neovascularization with no classic choroidal neovascularization. This
      subgroup included 166 of the 225 verteporfin-treated patients (74%) and 92 of the
      114 placebo-treated patients (81%). In these patients, 91 of the verteporfin
      treated group (55%) compared with 63 of the placebo-treated group (68%) lost at
      least 15 letters (P =.032), whereas 48 of the verteporfin-treated group (29%) and
      43 of the placebo-treated group (47%) lost at least 30 letters (P =.004). Other
      secondary outcomes, including visual acuity letter score worse than 34
      (approximate Snellen equivalent of 20/200 or worse), mean change in visual acuity
      letter score, development of classic choroidal neovascularization, progression of
      classic choroidal neovascularization and size of lesion, favored the verteporfin
      treated group at both the month 12 and month 24 examination for both the entire
      study group and the subgroup of cases with occult with no classic choroidal
      neovascularization at baseline. Subgroup analyses of lesions composed of occult
      with no classic choroidal neovascularization at baseline suggested that the
      treatment benefit was greater for patients with either smaller lesions (4 disc
      areas or less) or lower levels of visual acuity (letter score less than 65, an
      approximate Snellen equivalent of 20/50(-1) or worse) at baseline. Prospectively
      planned multivariable analyses confirmed that these two baseline variables
      affected the magnitude of treatment benefit. (ABSTRACT TRUNCATED)

PMID- 11336930
TI  - Clinical variations and complications of Coats disease in 150 cases: the 2000
      Sanford Gifford Memorial Lecture.
AB  - PURPOSE: The purpose of this report is to review the clinical variations and
      natural course of Coats disease, using strict diagnostic guidelines. METHODS: In
      a retrospective, consecutive series, Coats disease was defined as idiopathic
      retinal telangiectasia with intraretinal or subretinal exudation without
      appreciable signs of retinal or vitreal traction. We reviewed our experience with
      the clinical features, complications, and diagnostic approaches to Coats disease.
      RESULTS: In 150 consecutive patients (158 eyes), Coats disease was diagnosed at a
      median age of 5 years (range, 1 month to 63 years), occurred in 114 males (76%),
      and was unilateral in 142 patients (95%). There was no predilection for race or
      laterality. The most common referral diagnoses were Coats disease in 64 cases
      (41%) and retinoblastoma in 43 (27%). The first symptom or sign was decreased
      visual acuity in 68 cases (34%), strabismus in 37 (23%), leukocoria in 31 (20%),
      and 13 patients (8%) were asymptomatic. Visual acuity at presentation was 20/200
      to no light perception in 121 eyes (76%). The anterior segment was normal in 142
      eyes (90%). The retinal telangiectasia involved the midperipheral or peripheral
      fundus in 156 of the 158 eyes (99%) and was restricted to the macular area in two
      eyes (1%); involved mainly the temporal fundus in 66 eyes (42%), inferior fundus
      in 41 eyes (26%), and more than one sector in 34 eyes (22%). Retinal exudation
      was present in all 12 clock hours in 86 eyes (55%) and six or more clock hours in
      115 eyes (73%). There was a total retinal detachment in 74 eyes (47%) and
      neovascular glaucoma in 12 (8%). Retinal macrocysts were present in 18 eyes
      (11%), a vasoproliferative tumor in nine eyes (6%) and retinal neovascularization
      in four eyes (3%). Fluorescein angiography in 49 of the 158 eyes (37%) disclosed
      early hyperfluorescence of the telangiectasias and macular edema in 18 of eyes
      (37%). Ultrasonography typically showed a retinal detachment but no solid mass.
      CONCLUSIONS: Coats disease is a distinct clinical entity characterized by
      idiopathic retinal telangiectasia and retinal exudation. It is usually
      unilateral, occurs mostly in young males, and can cause severe visual loss
      resulting from exudative retinal detachment. The clinician should follow strict
      criteria in making the diagnosis, to avoid confusing Coats disease with other
      forms of exudative retinopathy.

PMID- 11336931
TI  - Classification and management of Coats disease: the 2000 Proctor Lecture.
AB  - PURPOSE: To review the methods and results of management in a large series of
      patients with Coats disease, to determine risk factors for poor visual outcome
      and enucleation, and to propose a practical classification of Coats disease.
      METHODS: In a retrospective consecutive series in 150 patients, Coats disease was
      defined as idiopathic retinal telangiectasia with intraretinal or subretinal
      exudation without appreciable signs of retinal or vitreal traction. We reviewed
      our experience with management, including observation, laser photocoagulation,
      cryotherapy, and various techniques of retinal detachment surgery and
      enucleation. The anatomic outcome, complications of treatment, visual results,
      and reasons for enucleation were tabulated. Factors predictive of poor visual
      outcome (20/200 or worse) and enucleation were determined using Cox proportional
      hazards regression models. Based on these observations, a staging classification
      of Coats disease, applicable to treatment selection and ocular prognosis, is
      proposed. RESULTS: In 117 patients (124 eyes) with a mean follow up of 55 months
      (range, 6 months to 25 years) primary management was observation in 22 eyes
      (18%), cryotherapy in 52 (42%), laser photocoagulation in 16 (13%), various
      methods of retinal detachment surgery in 20 (17%), and enucleation in 14 (11%).
      Anatomic improvement or stability was achieved in 76% of eyes, and final visual
      acuity was 20/50 or better in 17 eyes (14%), 20/60 to 20/100 in eight (6%),
      20/200 to finger counting in 30 (24%), and hand motion to no light perception in
      49 (40%) Enucleation was ultimately necessary in 20 eyes (16%). Risk factors
      predictive of poor visual outcome (20/200 or worse) included postequatorial (P
      =.01), diffuse (P =.01), or superior (P =.04) location of the telangiectasias and
      exudation, failed resolution of subretinal fluid after treatment (P =.02), and
      presence of retinal macrocysts (P =.02). The main risk factors for enucleation
      were elevated intraocular pressure (greater than 22 mm Hg; P less than or equal
      to.001) and iris neovascularization (P less than or equal to.001). Coats disease
      was classified into stage 1, telangiectasia only; stage 2, telangiectasia and
      exudation (2A, extrafoveal exudation; 2B, foveal exudation) stage 3, exudative
      retinal detachment (3A, subtotal; 3B, total); stage 4, total detachment and
      secondary glaucoma; and stage 5, advanced end-stage disease. Poor visual outcome
      (20/200 or worse) was found in 0% of eyes with stage 1, 53% with stage 2, 74%
      with stage 3, and 100% of stages 4 and 5 Coats disease. Enucleation was
      ultimately necessary in 0% of stages 1 and 2, 7% of stage 3, 78% of stage 4, and
      0% of stage 5 disease. CONCLUSIONS: Carefully selected treatment can anatomically
      stabilize or improve the eye with Coats disease in 76% of eyes. However, poor
      visual outcome of 20/200 or worse commonly results. Patients who present with
      stages 1 to 3 Coats disease have the best visual prognosis, and patients with
      stages 4 and 5 have a poor visual prognosis.

PMID- 11336932
TI  - Emotional distress in patients with retinal disease.
AB  - PURPOSE: To investigate the prevalence of, and potential risk factors for,
      emotional distress among patients with retinal disease. DESIGN: Cross-sectional
      study. METHODS: Cases consisted of 86 consecutive patients at Wilmer Eye
      Institute Retinal Vascular Center. Fifty-one controls with normal visual acuity
      and no known ocular disease were frequency-matched to the cases by age, sex, and
      race. Subjects were interviewed using the Community Disability Scale, a
      functional status questionnaire, and the General Health Questionnaire, a
      questionnaire assessing emotional distress. RESULTS: The prevalence of probable
      (General Health Questionnaire score 4 or greater and less than 10) or definite
      (General Health Questionnaire score 10 or greater) emotional distress was 59.3%
      among ophthalmic patients and 2.0% among controls. There were significant
      relationships between emotional distress, as assessed by General Health
      Questionnaire score, and degree of 1) visual impairment, as assessed by weighted
      bilateral average logarithm of minimal angle of resolution (logMAR), and 2)
      functional impairment, as assessed by Community Disability Scale score (P =.001).
      Univariate analyses identified significant predictors of emotional distress:
      shorter duration of ocular disease (P =.019), worse visual acuity (P =.001),
      increased systemic comorbidities (P =.001), and increased functional impairment
      (P <.001). Multiple regression analysis demonstrates that worse visual acuity,
      increased systemic comorbidities, and shorter duration of ocular disease each
      explain over 10% of the variability in General Health Questionnaire score (r(2) =
      0.15, 0.12, and 0.11, respectively). Addition of Community Disability Scale score
      to the regression model eliminates the significance of visual acuity and systemic
      comorbidities; Community Disability Scale score explains nearly 30% of the
      variability in emotional distress, as assessed by General Health Questionnaire
      score (r(2) = 0.29). CONCLUSIONS: Emotional distress is prevalent among patients
      with retinal disease; potential risk factors for emotional distress among such
      patients include shorter duration of ocular disease, worse visual acuity,
      increased systemic comorbidities, and increased functional impairment.

PMID- 11336933
TI  - Visual hallucinations in patients with retinal disease.
AB  - PURPOSE: To investigate the prevalence and phenomenologic nature of visual
      hallucinations among patients with retinal disease and to investigate whether
      presence of hallucinations is a significant predictor of functional status,
      quality of life, and/or emotional distress after adjusting for visual acuity.
      DESIGN: Cross-sectional study. METHODS: Eighty-six consecutive patients at the
      Wilmer Ophthalmologic Institute Retinal Vascular Center were interviewed using
      the Sickness Impact Profile, Community Disability Scale, General Health
      Questionnaire, Visual Phenomena Interview, Eysenck Personality Questionnaire, and
      Telephone Interview for Cognitive Status. RESULTS: The prevalence of visual
      hallucinations was 15.1%. Most were formed hallucinations in clear consciousness
      that lasted for seconds to minutes. The majority of patients had been
      experiencing visual hallucinations for less than 1 year (61.5%) or for 1 to 2
      years (23.1%). Only two of the 13 patients with hallucinations had informed a
      physician of their hallucinations. Univariate analyses revealed that variables
      significantly associated with experiencing hallucinations were female sex, worse
      visual acuity, bilateral visual impairment, emotional distress, decreased
      functional status, and decreased quality of life. Regression analysis
      demonstrated that among patients with relatively good vision, those who
      experienced hallucinations were more emotionally distressed and had a lower
      quality of life than patients without hallucinations. CONCLUSIONS: Visual
      hallucinations among patients with retinal disease are common, underdiagnosed,
      and not associated with cognitive deficits, abnormal personality traits, or a
      family or personal history of psychiatric morbidity. Among patients with
      relatively good vision, hallucinations are associated with increased emotional
      distress and decreased quality of life.

PMID- 11336934
TI  - Complications and prognostic factors in Vogt-Koyanagi-Harada disease.
AB  - PURPOSE: To identify associations between complications of disease and final
      visual acuity in patients with Vogt-Koyanagi-Harada disease and to identify
      prognostic factors for disease outcome. METHODS: All patients diagnosed with Vogt
      Koyanagi-Harada disease at the Doheny Eye Institute or the Los Angeles
      County/University of Southern California Medical Center between 1983 and 1997
      were reviewed. Data extracted included initial and final visual acuities, age,
      gender, ethnicity, complications, treatment, duration of disease, and number of
      recurrences. RESULTS: One hundred one patients with Vogt-Koyanagi-Harada disease
      were identified, 68 (67%) of which were female. Mean age was 34 +/- 14 years
      (range, 8 to 75 years). Asians presented at a significantly older age than all
      other groups. One hundred three eyes (51%) developed at least one complication,
      including cataract in 84 eyes (42%), glaucoma in 54 eyes (27%), choroidal
      neovascular membranes in 22 eyes (11%), and subretinal fibrosis in 13 eyes (6%).
      Patients who developed at least one complication had a significantly longer
      median duration of disease and number of recurrent episodes of inflammation (P
      =.0001 for each) than did those patients who developed no complications.
      Statistically significant associations existed between poor final visual acuity
      and greater numbers of complications (P =.001), greater age at onset (P =.03), a
      longer median duration of disease (P =.03), and greater number of recurrent
      episodes of inflammation (P =.0004). Eyes possessing a better visual acuity at
      presentation were more likely to have a better visual acuity at final follow-up
      (P =.001). CONCLUSIONS: Factors associated with a worse final acuity included
      increasing numbers of complications, greater age at onset, and worse acuity at
      presentation.

PMID- 11336935
TI  - Depigmented atrophic lesions in sunset glow fundi of Vogt-Koyanagi-Harada
      disease.
AB  - PURPOSE: Although the depigmented, small, round to oval lesions seen in the
      sunset glow fundi of Vogt-Koyanagi-Harada disease are considered to represent
      Dalen-Fuchs nodules, there is no histopathologic evidence to support such a
      consideration. An attempt is made herein to clarify the nature of the atrophic
      lesions and distinguish them from Dalen-Fuchs nodules seen in eyes with Vogt
      Koyanagi-Harada disease. METHODS: Eyes from five individuals with clinical
      diagnoses of Vogt-Koyanagi-Harada disease were subjected to histopathologic
      examination. The retinal pigment epithelial changes from early active to
      convalescent and late chronic recurrent stages were evaluated. Particular
      attention was paid to Dalen-Fuchs nodules, depigmented lesions in the sunset glow
      fundi, and hyperpigmentation of the chronic recurrent stage. RESULTS: Eyes of two
      individuals, one in the active stage of Vogt-Koyanagi-Harada disease and the
      other in the convalescent stage, showed the presence of Dalen-Fuchs nodules. The
      depigmented small retinal pigment epithelial lesions were seen in two
      individuals, both of whom exhibited the sunset glow fundus of the convalescent
      stage. The retinal pigment epithelial lesions represented damage or disappearance
      of retinal pigment epithelial cells, and the sunset glow fundus appearance was
      from the loss of choroidal melanocytes. The heavy pigmentation seen in fundi with
      the chronic recurrent stage was the result of the proliferation of retinal
      pigment epithelial cells. CONCLUSION: The Dalen-Fuchs nodule is a specific
      histologic change observed at the level of retinal pigment epithelium in patients
      with Vogt-Koyanagi-Harada disease. There is no histologic confirmation that the
      depigmented small atrophic lesions seen in the sunset glow fundi of Vogt-Koyanagi
      Harada disease are Dalen-Fuchs nodules. The depigmented lesions represent
      localized damage or disappearance of retinal pigment epithelial cells.

PMID- 11336936
TI  - An association between Vogt-Koyanagi-Harada disease and Guillain-Barre syndrome.
AB  - PURPOSE: To describe an association between Vogt-Koyanagi-Harada disease and
      Guillain-Barre syndrome. METHODS: Case series, describing three patients.
      RESULTS: In two patients, the disorders had their onsets within 2 weeks of each
      other; in the third patient, Vogt-Koyanagi-Harada disease occurred after 3
      months, as Guillain-Barre syndrome resolved. All three patients had bilateral
      panuveitis typical of Vogt-Koyanagi-Harada disease. Each also developed well
      accepted manifestations of Guillain-Barre syndrome, including paresis of the
      lower extremities (all patients), paresis of the upper extremities (two
      patients), paresis of cranial nerves (two patients), areflexia (all patients),
      and abnormal electromyography findings (two patients). CONCLUSIONS: Vogt-Koyanagi
      Harada disease may follow or occur simultaneously with Guillain-Barre syndrome.
      The fact that these two autoimmune disorders occur together in some patients
      suggest that they may share common disease mechanisms.

PMID- 11336937
TI  - Phacoemulsification cataract extraction and posterior chamber lens implantation
      in patients with uveitis.
AB  - PURPOSE: This study reports outcomes of phacoemulsification cataract extraction
      and posterior chamber intraocular lens implantation within the capsular bag in
      patients with uveitis. METHODS: We retrospectively reviewed the charts of 32
      patients (39 eyes) with uveitis who underwent phacoemulsification cataract
      extraction and posterior chamber intraocular lens implantation by two surgeons at
      The Cleveland Clinic Foundation from January 1990 to June 1998. Patients with
      less than 3 months of follow-up were excluded. RESULTS: Diagnoses of uveitis
      included idiopathic (15 eyes), sarcoidosis (10 eyes), pars planitis (four eyes),
      CMV retinitis (two eyes), Fuchs heterochromic iridocyclitis (two eyes), syphilis
      (two eyes), and one eye each of tuberculosis, Crohn's disease, HLA-B27
      associated, and acute retinal necrosis. Average follow-up was 20 months (range, 3
      to 63 months). Best-corrected visual acuity improved in 37 eyes (95%). Average
      improvement was 4 +/- 3 Snellen acuity lines (range, 1 to 10 lines). Thirty-four
      eyes (87%) attained final visual acuity better than or equal to 20/40. Visual
      loss occurred in one eye (3%) with CMV retinitis. No improvement in visual acuity
      was seen in one eye (3%) that developed a retinal pigment epithelial detachment.
      Posterior capsule opacification occurred in 24 eyes (62%), 12 of which required
      Nd:YAG capsulotomy (31%). Other postoperative complications included recurrence
      of uveitis (41%), cystoid macular edema (33%), epiretinal membrane formation
      (15%), and posterior synechiae (8%). CONCLUSIONS: Phacoemulsification cataract
      extraction with posterior chamber intraocular lens implantation is safe in
      patients with uveitis. The incidences of recurrence of uveitis, cystoid macular
      edema, epiretinal membrane, and posterior synechiae were lower than those
      reported previously for extracapsular cataract extraction.

PMID- 11336938
TI  - Glaucoma filtering bleb dysesthesia.
AB  - PURPOSE: To determine the prevalence and risk factors for glaucoma filtering bleb
      dysesthesia (discomfort). METHODS: A prospective cross-sectional observational
      study of consecutive patients with unilateral glaucoma filtering blebs from
      trabeculectomy was conducted. A self-report questionnaire was administered, which
      asked about the frequency and severity of the following symptoms: ocular pain,
      discomfort, burning, foreign body sensation, and tearing. The following variables
      were recorded by the investigators: age, race, sex, type and date of glaucoma
      surgery, antifibrotic agent used, intraocular pressure, location, thickness, and
      size of bleb, percent coverage of the bleb by the eyelid, angle that the bleb
      made to the cornea, and the presence of epithelial defects or dellen. Dysesthesia
      scores between the affected eye and control eye were compared using the paired
      Student t test. Risk factors for dysesthesia were evaluated using analysis of
      variance or Pearson correlation coefficient. RESULTS: A total of 97 patients were
      enrolled in the study. The mean total dysesthesia score (+/-SD, range) in the
      affected eye was 11.1 (+/-9.4, 0 to 42) and in the unaffected eye 3.4 (+/-4.9, 0
      to 25, P =.001). Factors that predisposed to dysesthesia included younger age (P
      =.005), superonasal location of bleb (P =.036), presence of bubbles (P =.028),
      and poor lid coverage (P =.013). The steeper the angle of the bleb to the cornea,
      which was an indirect measure of the height of the bleb, the more likely a
      patient was to have bubbles (P =.001). CONCLUSION: Eyes with glaucoma filtering
      blebs experience more dysesthesia than eyes without filtering blebs. Young age,
      superonasal bleb location, poor lid coverage, and bubble formation are all
      associated with glaucoma filtering bleb dysesthesia.

PMID- 11336939
TI  - The efficacy and safety of latanoprost 0.005% once daily versus brimonidine 0.2%
      twice daily in open-angle glaucoma or ocular hypertension.
AB  - PURPOSE: To evaluate the efficacy and safety of latanoprost 0.005% given
      topically every evening versus brimonidine 0.2% given topically twice daily in
      primary open-angle glaucoma or ocular hypertensive patients. METHODS: This was a
      multicenter, crossover, double-masked comparison. After a 28-day treatment-free
      period, patients with primary open-angle glaucoma or ocular hypertension were
      randomized for 6 weeks to brimonidine or latanoprost and then crossed over to the
      opposite treatment. At baseline and after each treatment period, patients
      underwent intraocular pressure measurements every 2 hours from 08:00 to 20:00.
      RESULTS: In 33 patients the mean baseline trough (08:00) was 23.2 +/- 2.1 mm Hg
      and the diurnal curve pressure was 19.8 +/- 2.7 mm Hg. The trough and diurnal
      intraocular pressures for brimonidine were 19.6 +/- 3.4 mm Hg and 17.6 +/- 2.2 mm
      Hg, respectively. Brimonidine statistically reduced the pressure from baseline at
      each time point except hours 10 and 12 (P =.14 and P =.21, respectively). For
      latanoprost, the trough and diurnal pressures were 16.2 +/- 2.9 mm Hg and 15.4 +/
      2.5 mm Hg, respectively, and the pressure was statistically reduced at each time
      point (P <.001) and for the diurnal curve (P <.001). When compared directly, the
      intraocular pressure level for latanoprost was lower than brimonidine for the
      diurnal pressure and at each time point (P <.05). One patient was discontinued
      early from latanoprost treatment because of eyelid swelling; also, latanoprost
      caused more hyperemia than brimonidine (P =.04). CONCLUSION: This study suggests
      latanoprost dosed daily in the evening statistically reduces intraocular pressure
      more during daytime and evening hours than brimonidine dosed twice daily.
      Brimonidine may not consistently decrease the pressure 10 and 12 hours past
      dosing from nontreated levels.

PMID- 11336940
TI  - A randomized double-masked crossover study comparing latanoprost 0.005% with
      unoprostone 0.12% in patients with primary open-angle glaucoma and ocular
      hypertension.
AB  - PURPOSE: To compare the intraocular pressure)-lowering effect and side effects of
      latanoprost 0.005% once daily with unoprostone 0.12% twice daily. METHODS: Sixty
      patients with primary open-angle glaucoma or ocular hypertension were randomized
      to receive either latanoprost once daily in the evening and placebo once daily in
      the morning, or unoprostone twice daily in the morning and evening. The study was
      double masked and followed a crossover design with two treatment periods of 1
      month separated by a 3-week washout period. The intraocular pressure was measured
      at 9 AM and 5 PM on the baseline and day 28 visits, and at 9 AM on day 2 and day
      14 visits of each treatment period. The 9 AM measurement was taken 2 hours and 13
      hours after the last drop of unoprostone and latanoprost, and the 5 PM
      measurement was at 10 and 21 hours, respectively. The mean of the measurements
      was calculated. Safety parameters were also recorded. RESULTS: Fifty-six patients
      completed both treatment periods and had intraocular pressure data available for
      evaluation. After 1 month of treatment, latanoprost significantly reduced
      intraocular pressure (mean +/- SEM) by 6.1 +/- 0.5 mm Hg (P <.001) and
      unoprostone by 4.2 +/- 0.4 mm Hg (P <.001) adjusted from an overall baseline of
      22.3 +/- 0.5 mm Hg and 23.2 +/- 0.4 mm Hg, respectively. The difference of 1.9 mm
      Hg between treatments was statistically significant in favor of latanoprost [P
      =.003, analysis of covariance (ANCOVA)]. Unadjusted analysis of responders using
      the percentage decrease in intraocular pressure showed that the proportion of
      responders in the latanoprost-treated group was greater than in the unoprostone
      treated group. Adverse ocular symptoms and findings were mild in both treatment
      groups. Eye redness and ocular irritation were the most frequently reported
      events. CONCLUSIONS: Latanoprost once daily was significantly more effective in
      reducing intraocular pressure compared with unoprostone twice daily after 1 month
      of treatment in patients with primary open-angle glaucoma and ocular
      hypertension. Both drugs were well tolerated with few ocular adverse events.

PMID- 11336941
TI  - Effects of topical unoprostone and latanoprost on acute and recurrent herpetic
      keratitis in the rabbit.
AB  - PURPOSE: To determine the effect of the topical ocular hypotensive drug,
      isopropyl unoprostone, a docosanoid molecule with very weak prostaglandin
      activity, on herpes keratitis in the rabbit eye. METHODS: For acute disease,
      rabbit corneas inoculated with the corticosteroid-sensitive F(MP)E strain of
      herpes simplex virus type 1 were treated with various combinations of 0.12%
      isopropyl unoprostone, latanoprost, trifluridine, benzalkonium chloride 0.02%,
      dexamethasone sodium phosphate, ketorolac tromethamine, or saline solution
      beginning 1 day after infection. Severity of keratitis was evaluated in a masked
      manner. For recurrent disease, rabbit corneas infected with McKrae strain herpes
      simplex virus type 1 were treated with unoprostone or saline solution on
      postinfection days 25 to 42, and the presence or absence of lesions was recorded.
      RESULTS: Eyes treated with unoprostone showed significantly less severe disease
      than saline-treated or latanoprost-treated eyes during acute infection.
      Unoprostone-treated and saline-treated eyes showed no significant difference in
      the frequency of recurrent lesions. Eyes treated with latanoprost and/or
      dexamethasone, separately or in combination, showed increased severity of acute
      herpes simplex virus keratitis, whereas benzalkonium chloride 0.02%--treated eyes
      showed no significant difference, compared with saline treatment. Trifluridine
      resulted in rapid healing. CONCLUSIONS: Unoprostone did not increase the severity
      or recurrence rate of herpes simplex virus keratitis. Unoprostone requires twice
      a-day administration, compared with once-a-day for latanoprost, and unoprostone
      lowers intraocular pressure less than latanoprost. Nevertheless, unoprostone's
      superior safety profile may make its use advantageous. Benzalkonium chloride
      alone did not make the keratitis worse.

PMID- 11336942
TI  - Revised diagnostic criteria for Vogt-Koyanagi-Harada disease: report of an
      international committee on nomenclature.
AB  - PURPOSE: To present revised criteria for the diagnosis of Vogt-Koyanagi-Harada
      disease, a chronic, bilateral, granulomatous ocular and multisystem inflammatory
      condition of unknown cause. METHODS: Diagnostic criteria and nomenclature were
      subjects of discussion at the First International Workshop on Vogt-Koyanagi
      Harada Disease on October 19-21, 1999, at the University of California, Los
      Angeles, Conference Center, Lake Arrowhead, California. A committee appointed by
      the workshop participants was charged with drafting revised criteria for Vogt
      Koyanagi-Harada disease, based on discussions held during the conference. This
      article is the consensus committee report. RESULTS: New criteria, taking into
      account the multisystem nature of Vogt-Koyanagi-Harada disease, with allowance
      for the different ocular findings present in the early and late stages of the
      disease, were formulated and agreed upon by the committee. These criteria are
      based on additional knowledge and experience of experts in the field and are
      believed to reflect disease features more fully than previously published
      criteria. CONCLUSIONS: The revised definition of Vogt-Koyanagi-Harada disease,
      with expanded diagnostic criteria, will facilitate performance of studies
      involving homogeneous populations of patients, at various stages of disease, that
      address unanswered questions regarding treatment and disease mechanisms.

PMID- 11336943
TI  - Postkeratoplasty keratoconus in a nonkeratoconus patient.
AB  - PURPOSE: To determine whether postkeratoplasty keratoconus is caused by a
      recurrence of the host disease or transferred from the donor. METHODS:
      Penetrating keratoplasty was performed on the right eye of a 73-year-old woman
      with pseudophakic bullous keratopathy; her other eye was normal. After
      keratoplasty, visual acuity decreased secondary to the appearance of irregular
      astigmatism, central corneal thinning, and stromal striae in the graft. A repeat
      keratoplasty was performed. Clinical corneal topographic analysis and
      histopathologic studies were performed. RESULTS: Clinical findings and
      histopathology of the corneal graft were consistent with keratoconus. The second
      graft has remained clear for 2 years without signs of keratoconus. CONCLUSION:
      Classic keratoconus developed in a corneal graft in a patient without preexisting
      keratoconus. This supports the theory that postkeratoplasty keratoconus may be
      secondary to transfer of the disease from the donor.

PMID- 11336944
TI  - Demonstration of retroiridal extension of an epithelial membrane by ultrasound
      biomicroscopy: a clinicopathologic correlation.
AB  - PURPOSE: To report the utilization of ultrasound biomicroscopy (UBM) in
      identifying the extension into the posterior segment of an epithelial membrane,
      as correlated by the histopathologic findings. METHOD: Case report. UBM findings
      before enucleation with histopathologic correlation. RESULTS: UBM demonstrated a
      membrane tracking from the posterior iris surface over the ciliary body and
      towards the retina. Light microscopic examination disclosed the epithelial nature
      of this membrane. CONCLUSION: UBM can identify extension of an epithelial
      membrane into the posterior segment and thereby guide the approach to surgical
      management.

PMID- 11336945
TI  - Tear in the trabecular meshwork caused by an airsoft gun.
AB  - PURPOSE: To report a case of a tear in the trabecular meshwork caused by an
      airsoft gun, a toy that propels a plastic bullet. METHODS: Case report. RESULTS:
      A 7-year-old Japanese boy sustained an ocular injury to the right eye from an
      airsoft gun. Ophthalmic examination 1 hour after the injury showed a best
      corrected visual acuity in the injured eye of hand motion, corneal abrasion and
      edema, hyphema, and commotio retinae. Gonioscopy 6 days after the injury revealed
      a tear in the trabecular meshwork as well as an angle recession. Ultrasound
      biomicroscopy (UBM) strongly suggested that the tear extended into Schlemm's
      canal. Corneal abrasion and edema, hyphema, and commotio retinae resolved over 10
      days, and best-corrected visual acuity improved to 20/15. Two months after the
      injury, the trabecular meshwork had not healed. CONCLUSION: Airsoft guns can
      cause a full-thickness tear in the trabecular meshwork, which may contribute to
      development of late-onset glaucoma. UBM is useful to evaluate the tomographic
      features of the disrupted trabecular meshwork. The potential force of airsoft
      guns to cause substantial ocular injuries should be recognized. Wearing ocular
      protection should be mandatory while playing with airsoft guns.

PMID- 11336946
TI  - The association of HLA class II with pars planitis.
AB  - PURPOSE: To investigate the association of HLA class II alleles with pars
      planitis. METHODS: Blood samples were obtained from 28 patients with pars
      planitis seen in the Department of Ophthalmology and Visual Sciences and the
      Barnes Retina Institute at Washington University, St. Louis, Missouri. RESULTS:
      HLA-DR15, one of the allelic subtypes of HLA-DR2, was present in 18 (64.3%) of 28
      patients vs. 10 (20%) of 50 controls (OR = 7.20, CI = 2.28--23.20, P =.0001). HLA
      DR51 (HLA-DRB 5) was present in 16 (57.1%) of 28 patients vs. 6 (12%) of 50
      controls (OR = 9.78, CI = 2.79--36.42, P =.0001). HLA-DR17 was present in eight
      (28.6%) of 28 patients vs. one (2%) of 50 controls (OR = 19.60, CI = 2.29--886.7,
      P =.0001). CONCLUSION: Pars planitis is associated with an increased frequency of
      the HLA-DR2 suballele, -DR15, HLA-DR51, and HLA-DR17. These results suggest an
      immunogenic predisposition exists to pars planitis.

PMID- 11336947
TI  - Same eye recurrence of acute retinal necrosis syndrome.
AB  - PURPOSE: To report same eye recurrence of acute retinal necrosis syndrome.
      METHODS: Two case reports. RESULTS: Acute retinal necrosis syndrome recurred in
      the left eye of a 60-year-old man 13 years after the initial episode, and
      recurred in the right eye of a 49-year-old woman 8 years after the initial
      episode. The recurrent necrotic lesions developed in normal appearing retina,
      unrelated to the location of the previous lesions. The recurrent lesions were
      successfully treated with acyclovir. CONCLUSION: Patients with acute retinal
      necrosis syndrome should be followed because of possible recurrence not only in
      the other eye but also in the same eye.

PMID- 11336948
TI  - Evolution of sarcoid granulomas of the retina.
AB  - PURPOSE: To report a case of a young woman with a history of sarcoidosis who
      developed retinal granulomas. METHODS: Case report. RESULTS: A 33-year old woman
      with history of sarcoidosis with involvement of the central nervous system,
      confirmed by skin biopsy, bronchoscopy, and neuroimaging, presented with visual
      loss and was found to have choroidal and optic nerve granulomas in the left eye,
      and subsequently developed retinal granulomas in the left eye. CONCLUSION:
      Retinal granuloma is a rare manifestation of sarcoidosis.

PMID- 11336949
TI  - Retinal pigment epithelial tear after transpupillary thermotherapy for choroidal
      neovascularization.
AB  - PURPOSE: To describe two patients who developed a retinal pigment epithelial tear
      after transpupillary thermotherapy for choroidal neovascularization. METHOD: Case
      reports. RESULTS: Retinal pigment epithelial (retinal pigment epithelium) tear
      developed in 2 (8%) of 25 eyes after transpupillary thermotherapy for occult
      choroidal neovascularization associated with age-related macular degeneration. In
      both eyes, the retinal pigment epithelium tear developed between the treatment
      session and first post-treatment examination. In both eyes, the visual acuity was
      unchanged, but the complication of retinal pigment epithelium tear may result in
      decreased visual acuity when transpupillary thermotherapy is performed in an eye
      with good initial visual acuity. CONCLUSION: Retinal pigment epithelium tear
      appears to occur more frequently after transpupillary thermotherapy for poorly
      defined choroidal neovascularization than after conventional laser
      photocoagulation for poorly defined choroidal neovascularization.

PMID- 11336950
TI  - Transient formed visual hallucinations following macular translocation for
      subfoveal choroidal neovascularization secondary to age-related macular
      degeneration.
AB  - PURPOSE: To report the occurrence of transient formed visual hallucinations
      following macular translocation. METHODS: Two case reports. RESULTS: Two white
      women aged 84 and 83 years with bilateral age-related macular degeneration and
      unilateral subfoveal choroidal neovascularization underwent macular translocation
      with punctate retinotomy (limited macular translocation) and chorioscleral
      infolding in the eye with neovascularization. They complained of formed visual
      hallucinations which began within 24 hours following macular translocation and
      ceased 7 and 3 days postoperatively, respectively. Their symptoms occurred in the
      presence of normal cognition, orientation and insight, were not associated with
      other psychiatric symptoms, and were characteristic of Charles Bonnet syndrome
      (CBS). CONCLUSION: The temporary deliberate retinal detachment and/or poor vision
      following macular translocation may be associated with postoperative CBS, and
      this report extends the spectrum of conditions associated with CBS.

PMID- 11336951
TI  - Macular hole after laser in situ keratomileusis and photorefractive keratectomy.
AB  - PURPOSE: To describe three myopic patients who developed unilateral macular hole
      after undergoing bilateral laser in situ keratomileusis or photorefractive
      keratectomy. METHODS: Case reports. RESULTS: Three eyes of three myopic patients
      developed a macular hole in one eye after bilateral laser in situ keratomileusis
      or photorefractive keratectomy. The macular hole formed between 4 to 7 weeks
      after laser in situ keratomileusis in case 1 (a 48-year-old woman), and within 2
      months after laser in situ keratomileusis in case 2 (a 36-year-old woman). In
      case 3 (a 45-year-old man), the macular hole was found 9 months after
      photorefractive keratectomy. A vitrectomy closed the macular hole of case 1 with
      final best-corrected visual acuity of 20/25 and case 2 with 20/30, whereas case 3
      declined further surgery. CONCLUSION: A macular hole may develop in myopic eyes
      after laser in situ keratomileusis or photorefractive keratectomy. Vitreoretinal
      interface changes may play a role.

PMID- 11336952
TI  - Central retinal artery occlusion as the initial sign of aortic valve papillary
      fibroelastoma.
AB  - PURPOSE: We describe a central retinal artery occlusion in a young man who was
      subsequently found to have an aortic valve papillary fibroelastoma. METHODS: Case
      report with clinical, echocardiographic, and histopathologic observations.
      RESULTS: The aortic valve papillary fibroelastoma was successfully treated with
      tumor resection. CONCLUSION: Appropriate investigations in young patients with
      central retinal artery occlusion should therefore be conducted, including
      transthoracic and transesophageal echocardiography, to diagnose and treat this
      tumor, because failure to diagnose this tumor may result in further embolic
      events, including stroke and sudden death.

PMID- 11336953
TI  - Central retinal vein occlusion in a patient with thrombotic thrombocytopenic
      purpura.
AB  - PURPOSE: To describe the occurrence of central retinal vein occlusion in a
      patient with thrombotic thrombocytopenic purpura. METHODS: Case report. RESULTS:
      A 52-year-old woman developed central retinal vein occlusion in the acute phase
      of thrombotic thrombocytopenic purpura, followed by iris neovascularization only
      1 month after the onset of central retinal vein occlusion. Color Doppler imaging
      of the affected eye showed an increased resistive index of the central retinal
      artery and reduced blood flow velocity of the central retinal vein compared to
      the fellow eye. CONCLUSION: We describe a rare association between central
      retinal vein occlusion and thrombotic thrombocytopenic purpura with rapid
      evolution of iris neovascularization. Our case demonstrates that close
      ophthalmologic attention is important in thrombotic thrombocytopenic purpura.

PMID- 11336954
TI  - Reversal of nonarteritic anterior ischemic optic neuropathy associated with
      coexisting primary antiphospholipid syndrome and Factor V Leiden mutation.
AB  - PURPOSE: To report nonarteric anterior ischemic optic neuropathy (NAION) as an
      ocular manifestation in a woman with combined primary antiphospholipid syndrome
      and Factor V Leiden (FVL) mutation. METHODS: Case report of a middle-aged woman
      with hematological investigations confirming the diagnosis of both primary
      antiphospholipid syndrome and Factor V Leiden mutation, who presented with visual
      disturbance in her left eye. RESULTS: NAION was noted in her left eye. The
      patient was promptly treated with low molecular weight heparin, followed by
      warfarin, which resulted in the reversal of the ischemic optic neuropathy.
      CONCLUSIONS: Primary antiphospholipid syndrome and coexisting Factor V Leiden
      mutation should be considered in the differential diagnosis of NAION. Prompt
      treatment with anticoagulants can result in the reversal of the ischemic process.

PMID- 11336955
TI  - Internal carotid artery hypoplasia presenting as anterior ischemic optic
      neuropathy.
AB  - PURPOSE: To describe the occurrence of anterior ischemic optic neuropathy in a
      young woman with internal carotid artery hypoplasia. METHODS: Case report with
      clinical and radiologic observations. RESULTS: A 38-year-old woman suffered from
      a sudden, painless loss of vision in her right eye. The diagnosis of anterior
      ischemic optic neuropathy was based on the clinical course and appearance of the
      fundus. Doppler evaluation of the carotid arteries, computed tomography (CT)
      scan, magnetic resonance imaging (MRI), and CT angiogram all demonstrated
      internal carotid artery hypoplasia on the same side. CONCLUSION: Although carotid
      artery disease (mainly atherosclerosis) is not a common predisposing factor for
      anterior ischemic optic neuropathy, our patient had an ipsilateral coexisting
      internal carotid artery hypoplasia and anterior ischemic optic neuropathy. We
      believe that the carotid artery anomaly might have contributed to the development
      of anterior ischemic optic neuropathy in this patient.

PMID- 11336956
TI  - Light-induced amaurosis fugax.
AB  - PURPOSE: To describe an important symptom of bilateral amaurosis precipitated by
      exposure to bright light. METHODS: Case report. Clinical analysis of transient,
      painless, asymmetrical visual loss occurring in bright light in a 54-year-old
      man. RESULTS: Carotid ultrasound showed bilateral carotid disease. Carotid
      angiography demonstrated occlusion of the left internal carotid artery and severe
      stenosis of the right internal carotid artery and both external carotid arteries.
      Visual symptoms and an abnormal photostress test completely remitted after a
      right carotid endarterectomy. CONCLUSION: Light-induced amaurosis is an
      unfamiliar manifestation of ocular ischemic syndrome occurring with severe, often
      bilateral, carotid artery disease. Its recognition is important because the
      complaint is associated with severe carotid occlusive disease and recognition is
      necessary for timely surgical intervention because of the major risk for stroke.

PMID- 11336957
TI  - Vascular compression as a cause of superior oblique myokymia disclosed by thin
      slice magnetic resonance imaging.
AB  - PURPOSE: To describe a case of superior oblique myokymia in which thin-slice
      magnetic resonance imaging (MRI) appeared to show vascular compression of the
      trochlear nerve. METHODS: A 50-year-old woman presented with episodic monocular
      oscillopsia. Neuro-ophthalmologic examinations showed intermittent intorsional
      microtremor of her right eye, diagnosed as right superior oblique myokymia. Thin
      slice (1.6 mm) MRI, using spoiled gradient recalled acquisition in the steady
      state, was employed to examine the trochlear nerve in its course through the
      ambient cistern. RESULTS: Imaging disclosed a branch of the posterior cerebral
      artery immediately adjacent to the right trochlear nerve. CONCLUSION: These
      magnetic resonance findings suggest that a cause of superior oblique myokymia may
      be vascular compression of the trunk of the trochlear nerve.

PMID- 11336958
TI  - Rosai-Dorfman disease presenting as bilateral lacrimal gland enlargement.
AB  - PURPOSE: To report a patient with bilateral lacrimal gland enlargement as the
      initial manifestation of Rosai--Dorfman disease. METHODS: Case report. RESULTS: A
      14-year-old female presented with left lacrimal gland enlargement followed by
      right lacrimal gland enlargement 11 weeks later. Bilateral lacrimal gland
      biopsies were performed, and histopathologic examination revealed the diagnosis
      of Rosai--Dorfman disease. CONCLUSION: Patients with Rosai--Dorfman disease may
      present with bilateral lacrimal gland swelling in the absence of lymphadenopathy.
      Rosai--Dorfman disease should be considered in the differential diagnosis of
      bilateral lacrimal gland enlargement.

PMID- 11336972
TI  - Inter-species differences in drug properties.
AB  - There has been a clear trend towards decreased reliance upon animal studies and
      increased emphasis upon experiments with human-derived tissues. Nonetheless, we
      continue to need investigations of interspecies differences for two principal
      reasons: (1) to prospectively design experiments so that the animal species most
      similar to humans can be chosen, on a case-by-case basis, for each drug; (2) to
      properly evaluate and interpret data obtained from the experiments ("risk
      assessment"). Four core examples derived from the work in our FDA laboratory are
      used to illustrate these points. For paclitaxel, different metabolites were
      formed in humans and rats, which makes metabolic drug-drug interaction studies in
      rats irrelevant. For zidovudine (AZT), rapid glucuronidation in humans produced a
      much shorter half-life than expected from studies in animals, which have
      negligible glucuronidation. The toxicology and efficacy of both parent drug and
      metabolite need to be assessed in cases such as iododeoxydoxorubicin, in which
      the parent molecule is the dominant circulating species in mice, but patients
      have more than 10-fold greater exposure to the metabolite compared with the
      parent. While rats have highly-active arylamine N-acetyltransferases, dogs
      totally lack this enzyme family, and humans have intermediate amounts. For some
      situations, we've suggested that it can be desirable to inhibit NAT to make the
      human exposure more similar to dogs. In conclusion, although the ratio of
      animal:human data is decreasing, our ability to use animal data effectively for
      drug development has actually increased. Continued focus should be placed upon
      the application of comparative interspecies data for prospective design of animal
      experiments and retrospective interpretation of animal findings in terms of the
      potential for human risk and benefit.

PMID- 11336973
TI  - A comparison of aroclor 1254-induced and uninduced rat liver microsomes to human
      liver microsomes in phenytoin O-deethylation, coumarin 7-hydroxylation,
      tolbutamide 4-hydroxylation, S-mephenytoin 4'-hydroxylation, chloroxazone 6
      hydroxylation and testosterone 6beta-hydroxylation.
AB  - Aroclor 1254-induced rat liver homogenate supernatant (liver S-9) is routinely
      used as an exogenous metabolic activation system for the evaluation of
      mutagenicity of xenobiotics. The purpose of this study is to evaluate whether
      results obtained with Aroclor 1254-induced liver microsomes would be relevant to
      human. Aroclor 1254-induced and uninduced rat liver microsomes were compared to
      human liver microsomes in the metabolism of substrates which are known to be
      selectively metabolized by the major human cytochrome P450 (CYP) isoforms. The
      activities studied and the major CYP isoforms involved were as follows:
      phenacetin O-deethylation (CYP1A2); coumarin 7-hydroxylation, (CYP2A6);
      tolbutamide 4-hydroxylation (CYP2C9), S-mephenytoin 4'-hydroxylation (CYP2C19);
      dextromethorphan O-demethylation (CYP2D6); chloroxazone 6-hydroxylation (CYP2E1);
      and testosterone 6beta-hydroxylation (CYP3A4). We found that both induced and
      uninduced rat liver microsomes were active in all the pathways studied with the
      exception of coumarin 7-hydroxylation. Coumarin 7-hydroxylation was observed with
      human liver microsomes but not the rat liver microsomes. Aroclor-1254 was found
      to induce all activities measured, with the exception of coumarin 7
      hydroxylation. Dextromethorphan O-deethylation activity was higher in the rat
      liver microsomes than the human liver microsomes. Testosterone 6beta
      hydroxylation activity was found to be similar between the human liver microsomes
      and the induced rat liver microsomes. Our results suggest that experimental data
      obtained with Aroclor 1254-induced rat liver microsomes may not always be
      relevant to human.

PMID- 11336974
TI  - Metabolic, idiosyncratic toxicity of drugs: overview of the hepatic toxicity
      induced by the anxiolytic, panadiplon.
AB  - Preclinical drug safety evaluation studies, typically conducted in two or more
      animal species, reveal and define dose-dependent toxicities and undesirable
      effects related to pharmacological mechanism of action. Idiosyncratic toxic
      responses are often not detected during this phase in development due to their
      relative rarity in incidence and differences in species sensitivity. This paper
      reviews and discusses the metabolic idiosyncratic toxicity and species
      differences observed for the experimental non-benzodiazepine anxiolytic,
      panadiplon. This compound produced evidence of hepatic toxicity in Phase 1
      clinical trial volunteers that was not predicted by rat, dog or monkey
      preclinical studies. However, subsequent studies in Dutch-belted rabbits revealed
      a hepatic toxic syndrome consistent with a Reye's Syndrome-like idiosyncratic
      response. Investigations into the mechanism of toxicity using rabbits and
      cultured hepatocytes from several species, including human, provided a sketch of
      the complex pathway required to produce hepatic injury. This pathway includes
      drug metabolism to a carboxylic acid metabolite (cyclopropane carboxylic acid),
      inhibition of mitochondrial fatty acid beta-oxidation, and effects on
      intermediary metabolism including depletion of glycogen and disruption of glucose
      homeostasis. We also provide evidence suggesting that the carboxylic acid
      metabolite decreases the availability of liver CoA and carnitine secondary to the
      formation of unusual acyl derivatives. Hepatic toxicity could be ameliorated by
      administration of carnitine, and to a lesser extent by pantothenate. These
      hepatocellular pathway defects, though not directly resulting in cell death,
      rendered hepatocytes sensitive to secondary stress, which subsequently produced
      apoptosis and hepatocellular necrosis. Not all rabbits showed evidence of hepatic
      toxicity, suggesting that individual or species differences in any step along
      this pathway may account for idiosyncratic responses. These differences may be
      roughly applied to other metabolic idiosyncratic hepatotoxic responses and
      include variations in drug metabolism, effects on mitochondrial function,
      nutritional status, and health or underlying disease.

PMID- 11336975
TI  - Species comparison in P450 induction: effects of dexamethasone, omeprazole, and
      rifampin on P450 isoforms 1A and 3A in primary cultured hepatocytes from man,
      Sprague-Dawley rat, minipig, and beagle dog.
AB  - Induction of P450 isoforms 1A (CYP1A) and 3A (CYP3A) by model inducers
      dexamethasone, omeprazole and rifampin was evaluated in primary cultured
      hepatocytes from man and laboratory animals. Inducer-specific species-differences
      were observed. Results with human hepatocytes from six human donors consistently
      show that both rifampin and dexamethasone were inducers of CYP3A activity
      (measured as testosterone 6beta-hydroxylase activity), with rifampin being more
      potent. Conversely, in rat hepatocytes, dexamethasone was a potent CYP3A inducer
      while rifampin was not an inducer. Rifampin but not dexamethasone induced CYP3A
      in minipig and beagle dog hepatocytes. Omeprazole was a potent inducer of CYP1A
      activity (measured as ethoxyresorufin-O-deethylase activity) in human, beagle dog
      and minipig hepatocytes, and not an inducer in rat hepatocytes. The species
      differences observed suggest that human hepatocytes represent the most
      appropriate preclinical experimental system for the evaluation of P450 induction
      in human.

PMID- 11336976
TI  - Pregnane X receptor: molecular basis for species differences in CYP3A induction
      by xenobiotics.
AB  - Determining the molecular basis for the observed species differences in the
      xenobiotic-mediated induction of cytochrome 3A (CYP3A) gene expression has become
      one of the biggest dilemmas of the modern era in toxicology. Recently, a novel
      orphan nuclear receptor, termed pregnane X receptor (PXR), has been implicated to
      play a key role in the regulation of CYP3A genes by xenobiotics. PXR is capable
      of binding to and activating transcription from specific response elements found
      in the CYP3A gene promoter from multiple species. Notably, compounds that are
      known to induce CYP3A selectively in human, mouse, rat, or rabbit also activate
      the corresponding PXR. Pregnenolone 16alpha-carbonitrile, a known CYP3A inducer
      in rodents, is a very efficacious activator of mouse and rat PXR, whereas
      rifampicin, a known inducer of CYP3A in humans and rabbits, is a very efficacious
      activator of human and rabbit PXR. Likewise, selective activators of PXR also
      induce CYP3A gene expression in the corresponding species. Orthologous receptors
      from human, mouse, rat, and rabbit have been cloned and characterized and share
      approx. 95% identity in their DNA binding domains. By contrast, they share only
      75-80% identity in their amino acid sequences in the ligand-binding domain.
      Together, these data suggest that PXR is a critical regulator of CYP3A gene
      expression and activation of PXR is predictive of CYP3A induction. Furthermore,
      sequence differences in the ligand-binding domain, and not the DNA binding
      domain, appear to serve as the molecular basis for the species differences in
      CYP3A induction observed in vivo.

PMID- 11336977
TI  - Induction of intestinal cytochrome P450 (CYP3A) by rifampicin in beagle dogs.
AB  - Both male and female beagle dogs (four dogs/sex) were orally treated with
      rifampicin (Rif) at the dose of 10 mg/kg/day for 7 days and an additional eight
      dogs (four dogs/sex) were used as a control. The inducible effect of Rif on
      intestinal cytochrome P450, especially CYP3A enzyme, was investigated by
      measuring microsomal testosterone 6beta-hydroxylation (6beta-OHT) activity,
      immunoblot and ELISA analysis. In male dogs, microsomal 6beta-OHT activity in the
      duodenum, upper, middle and lower part of the jejunum and the ileum of the
      control was 229, 204, 194, 129 and 57 pmol/min/mg protein, while the activity of
      the Rif-treated dogs significantly increased to 456, 486, 430, 192 and 138
      pmol/min/mg protein, respectively. The activity of intestinal 6beta-OHT in the
      control and Rif-treated female dogs showed almost similar levels to those
      observed in the corresponding male dogs. The activity of intestinal 6beta-OHT in
      both control and Rif-treated dogs was specifically inhibited by anti-CYP3A12
      antiserum. The apparent K(m) value for 6beta-OHT activity in all sections of the
      small intestine was comparable with that in the liver, and no significant changes
      were observed in between control and Rif-treated dogs. In both control and Rif
      treated dogs, immunoblotting of intestinal microsomes with anti-CYP3A12 antiserum
      produced a band indistinguishable from that of purified CYP3A12 or of
      immunoreactive CYP3A12 in liver microsomes. A significant increase in intestinal
      CYP3A content by Rif treatment was quantitatively verified by the ELISA analysis
      and the magnitude of its increase correlated well with that of 6beta-OHT activity
      elevation. Furthermore, the results of immunohistochemistry using the anti
      CYP3A12 antiserum indicated that CYP3A protein was specifically distributed in
      epithelial cells throughout the small intestine and appeared to be predominant at
      the apical side of villus cells. These results demonstrate that Rif induces not
      only hepatic CYP3A12 but also intestinal CYP3A in dogs.

PMID- 11336978
TI  - Extent of CpG methylation is not proportional to the in vivo spontaneous mutation
      frequency at transgenic loci in Big Blue rodents.
AB  - The lacI transgene used in the Big Blue (BB) mouse and rat mutation assays
      typically displays spontaneous mutation frequencies in the 5x10(-5) range.
      Recently, the bone marrow and bladder of the Big Blue rat were reported to have,
      by an order of magnitude, the lowest spontaneous mutation frequencies ever
      observed for lacI in a transgenic animal, approaching the value for endogenous
      targets such as hprt ( approximately 10(-6)). Since spontaneous mutations in
      transgenes have been attributed in part to deamination of 5-methylcytosine in CpG
      sequences, we have investigated the methylation status of the lacI transgene in
      bone marrow of BB rats and compared it to that present in other tissues including
      liver, spleen, and breast. The first 400 bases of the lacI gene were investigated
      using bisulfite genomic sequencing since this region contains the majority of
      both spontaneous and induced mutations. Surprisingly, all the CpG cytosines in
      the lacI sequence were fully methylated in all the tissues examined from both 2-
      and 14-week-old rats. Thus, there is no correlation between 5-methylcytosine
      content at CpG sites in lacI and the frequency of spontaneous mutation at this
      marker. We also investigated the methylation status of another widely used
      transgenic mutation target, the cII gene. The CpG sites in cII in BB rats were
      fully methylated while those in BB mice were partially methylated (each site
      approximately 50% methylated). Since spontaneous mutation frequency at cII is
      comparable in rat and mouse, the methylation status of CpG sequences in this gene
      also does not correlate with spontaneous frequency. We conclude that other
      mechanisms besides spontaneous deamination of 5-methylcytosine at CpG sites are
      driving spontaneous mutation at BB transgenic loci.

PMID- 11336979
TI  - Radiation induced apoptosis in ataxia telangiectasia homozygote, heterozygote and
      normal cells.
AB  - Recent reports suggest that the radiation-induced, p53-dependent, apoptotic
      response is aberrant in ataxia telangiectasia (AT) cells. We investigated the
      possibility that an aberrant apoptotic response to ionizing radiation may also be
      the characteristic of AT heterozygotes and may facilitate in discriminating AT
      heterozygotes from the general population. Log phase, Epstein Barr virus (EBV)
      transformed lymphoblastoid cell lines and primary lymphocytes from three AT
      families were irradiated and the apoptotic response at 30h post radiation was
      measured by flow cytometry using TUNEL and hypodiploid methods. Our results show
      that the apoptotic response of AT homozygote (ATM-/-), AT heterozygote (ATM+/-)
      and normal cells (ATM+/+) to ionizing radiation, measured by the hypodiploid and
      TUNEL methods using flow cytometry, is dose and time dependent. Furthermore, this
      response is paradoxical in that ATM (-/-) lymphoblastoid cells were characterized
      by a reduced post radiation apoptotic response compared to their normal
      counterparts. Heterozygote (ATM+/-) lymphoblastoid cells displayed an
      intermediate response to ionizing radiation. In contrast, primary, non
      transformed AT cells exhibited the same apoptotic response as their normal
      counterparts. Our results thus indicate that pre-radiation, EBV-transformed,
      lymphoblastoid cell lines from individual families may be useful in
      discriminating ATM status, but patient-derived, primary AT homozygous,
      heterozygous and normal primary cultured lymphocytes cannot be discriminated by
      this assay.

PMID- 11336980
TI  - In vitro replication and mutagenesis of a novel reversion vector with selective
      DNA damage in the supF gene.
AB  - The ability to detect the most common type of UV-induced mutation, the C to T
      transition, at the previously characterized hotspot at position 99 of the supF
      gene has been demonstrated in a selectively irradiated reversion vector,
      pLS189(Rev). The supF region was amplified, irradiated with 500J/m(2) UVC or
      unirradiated, and ligated into the pLS189(Rev) plasmid. A portion of ligated
      product plasmid containing the irradiated fragment was sensitive to nicking by T4
      endonuclease V, indicating the presence of the most common type of UV-induced
      damage, the pyrimidine dimer. Plasmid containing the irradiated or unirradiated
      supF gene was replicated completely in cellular extracts from either HeLa or XP-A
      cells in vitro. Plasmid containing the irradiated supF gene showed an inhibition
      of total replication to a level similar to those of previous studies with plasmid
      molecules exposed in their entirety to 40J/m(2). Replication of selectively
      irradiated plasmid resulted in an average reversion frequency of 0.071% in the
      two extracts; a 42-fold increase over the average spontaneous reversion frequency
      of unirradiated plasmid. The reversion frequencies were not significantly
      different between extracts prepared from HeLa and XP-A cells, indicating that
      neither the repair status of the cell lines nor the XPA protein itself affect the
      frequency of C to T transitions at position 99 of the supF gene in plasmid
      replicated in vitro. These data indicate that the plasmid pSL189(Rev), containing
      the selectively UV-irradiated supF gene, is a useful and sensitive tool to study
      mutagenesis at a specific site. This approach may be applicable to the
      investigation of other environmental DNA-damaging agents, by allowing the target
      gene to be selectively damaged while maintaining the ability of the plasmid to
      replicate completely. Such a system, amenable to biochemical manipulation, may be
      very valuable in elucidating the function of novel proteins in the process of
      mutagenesis.

PMID- 11336981
TI  - Identification of a deletion hotspot on distal mouse chromosome 4 by YAC
      fingerprinting.
AB  - Using repetitive elements as probes, genomic DNA fingerprints of four randomly
      selected yeast artificial chromosome (YAC) clones (two human and two mouse
      derived YAC) were analyzed to determine the mutation level following X-ray
      exposure. Because the repetitive probes were derived from the mammalian host DNA,
      most of the fingerprint bands originated from the artificial chromosomes and not
      from the yeast genome. For none of the YAC clones was the mutation frequency
      elevated following X-ray exposure. However, for one mouse-derived YAC, the
      mutation level was unusually high (7%; 42 mutants of 607 clones analyzed),
      whereas for the other three YACs, the mutation level was nearly 0%. Surprisingly,
      40 of the 42 mutations were deletions occurring only at three of the 20 mouse
      specific fingerprint bands. One of the frequently deleted fragments was cloned,
      sequenced and mapped to distal mouse chromosome 4, which has been repeatedly
      reported to be the most unstable region of the whole mouse genome, associated
      with various tumors. Deletion mapping of six YAC mutants revealed this fragment
      to be completely deleted in four YACs. In the other two mutants, recombination
      occurred within the fragment, in each case initiated at the same LINE-1 element.
      In conclusion, the presented YAC fingerprint is a useful tool for detecting and
      characterizing unstable regions in mammalian genomes.

PMID- 11336983
TI  - Involvement of eddy currents in the mutagenicity of ELF magnetic fields.
AB  - Possible carcinogenic and/or mutagenic activity of extremely low frequency
      magnetic fields was examined using somatic mutation and recombination test system
      of Drosophila melanogaster. An X-linked semi-dominant DNA repair defective
      mutation mei-41(D5) was introduced into the conventional mwh/flr test system to
      enhance mutant spot frequency. Virgin females of w mei-41(D5)/FM6; flr/TM6 were
      crossed with w mei-41(D5)/Y; mwh jv; spa(pol) males. The F(1) third instar larvae
      were exposed to a 50Hz, 20mT sinusoidal AC magnetic field for 24h. After moulting
      from pupal cases, their wings were examined under a bright field microscope to
      detect hair spots with mwh or flr mutant morphology. The exposure caused a
      statistically significant enhancement in somatic recombination spot frequency.
      Mutant spots arising due to chromosomal non-disjunction or terminal deletion also
      increased but the frequency of spots resulting from point mutation was not
      altered. The enhancement in the recombination spot frequency was suppressed to
      the control level when a culture medium without electrolytes was used during
      exposure. When larvae were exposed to a magnetic field in an annular dish, flies
      from the outer ring showed more mutant spots compared to those from the inner
      ring. These results suggest that the detected mutagenic activity was that of the
      induced eddy current, rather than that of the magnetic field itself.

PMID- 11336982
TI  - Molecular description of three macro-deletions and an Alu-Alu recombination
      mediated duplication in the HPRT gene in four patients with Lesch-Nyhan disease.
AB  - Mutations in the HPRT gene cause a spectrum of diseases that ranges from
      hyperuricemia alone to hyperuricemia with profound neurological and behavioral
      dysfunction. The extreme phenotype is termed Lesch-Nyhan syndrome. In 271 cases
      in which the germinal HPRT mutation has been characterized, 218 different
      mutations have been found. Of these, 34 (13%) are large- (macro-) deletions of
      one exon or greater and four (2%) are partial gene duplications. The deletion
      breakpoint junctions have been defined for only three of the 34 macro-deletions.
      The molecular basis of two of the four duplications has been defined. We report
      here the breakpoint junctions for three new deletion mutations, encompassing
      exons 4-8 (20033bp), exons 4 and 5 (13307bp) and exons 5 and 6 (9454bp),
      respectively. The deletion breakpoints were defined by a combination of long
      polymerase chain reaction (PCR) amplifications, and conventional PCR and DNA
      sequencing. All three deletions are the result of non-homologous recombinations.
      A fourth mutation, a duplication of exons 2 and 3, is the result of an Alu
      mediated homologous recombination between identical 19bp sequences in introns 3
      and 1. In toto, two of three germinal HPRT duplication mutations appear to have
      been caused by Alu-mediated homologous recombination, while only one of six
      deletion mutations appears to have resulted from this type of recombination
      mechanism. The other five deletion mutations resulted from non-homologous
      recombination. With this admittedly limited number of characterized macro
      mutations, Alu-mediated unequal homologous recombinations account for at least 8%
      (3 of 38) of the macro-alterations and 1% (3 of 271) of the total HPRT germinal
      mutations.

PMID- 11336984
TI  - Molecular characterisation of camptothecin-induced mutations at the hprt locus in
      Chinese hamster cells.
AB  - The capacity of the topoisomerase I inhibitor camptothecin (CPT) to induce single
      locus mutations at the hypoxanthine-guanine phosphoribosyltransferase (hprt) gene
      and the DNA changes underlying induced mutations were analysed in Chinese hamster
      ovary cells. Camptothecin treatments increased hprt mutations up to 50-fold over
      the spontaneous levels at highly cytotoxic doses. Genomic DNA was isolated from 6
      thioguanine resistant clones and subjected to multiplex PCR to screen for gross
      alterations in the gene structure. The molecular analysis revealed that deletion
      mutants represented 80% of the analysed clones, including total hprt deletion,
      multiple and single exon deletions. Furthermore, a fraction of the analysed
      clones showed deletions of more than one exon that were characterised by the
      absence of non-contiguous exons. These data show that single locus mutations
      induced by camptothecin are characterised by large deletions or complex
      rearrangements rather than single base substitutions and suggest that the
      recombinational repair of camptothecin-induced strand breaks at replication fork
      may be involved in the generations of these alterations at the chromatin
      structure level.

PMID- 11336985
TI  - As to the clastogenic-, sister-chromatid exchange inducing-and cytotoxic activity
      of inosine triphosphate in cultures of human peripheral lymphocytes.
AB  - The influence of commercial inosine triphosphate (ITP) on the chromosome
      aberration rate, the mitotic rate, sister-chromatid exchange (SCE) frequency, and
      the proportion of first (X1), second (X2) and third (X3) division metaphases was
      investigated in 72h cultures of human peripheral lymphocytes. The blood donors
      had mild inactive arthrosis and a normal health check-up. All cultures of each
      volunteer were set-up simultaneously. In contrast to a previous report [Arch.
      Biochem. Biophys. 278 (1990) 238-244], it was demonstrated in two preliminary
      studies (number of subjects, n=5 each) that ITP at a final concentration of 100
      microM does not induce chromosomal aberrations and, furthermore, that not ITP
      concentrations higher than 100 microM but ITP doses higher than 3.8mM prohibit
      culture growth. Based on these results, cultures with a final ITP concentration
      of 3.6mM (max.) and 1.8mM (max./2) were compared with control cultures (number of
      subjects n=10; three males and seven females, mean age x=57.6 years). Whereas no
      increase in the chromosomal breakage rate was observed in cultures with an ITP
      concentration of 1.8mM and only a marginally significant one (P=0.048) for 3.6mM
      ITP cultures, a highly significant induction of SCEs, not only at an ITP
      concentration of 3.6mM (P<0.0001) but also at 1.8mM (P<0.0001) was seen. The
      increase in the SCE frequency was not linear, but steeper from 0 to 1.8mM than
      from 1.8 to 3.6mM. Nevertheless, the difference between 1.8 and 3.6mM cultures
      was significant (P=0.027). The distribution of the number of SCEs per metaphase
      as well as the distribution of SCEs per chromosome correspond to the expected
      Poisson values. The investigation of the cytotoxic effect of the studied ITP
      concentrations revealed a highly significant reduction of the mitotic rate from 0
      to 1.8mM as well as from 1.8 to 3.6mM in the aberration studies (all P values are
      equal to smallest possible one for a sample size of 10, namely, 0.002), and in
      the SCE studies there is a significant decrease in the X3 frequency when ITP is
      increased (0-1.8mM: P=0.0061 and 1.8-3.6mM: P<0.0001). The proportion of X1
      within all X1 and X2 metaphases changes significantly only at the second dose
      step (0-1.8mM ITP: P=0.22 and 1.8-3.6mM ITP: P<0.0001). The results are
      discussed.

PMID- 11336986
TI  - In vivo mutant frequency of thioguanine-resistant T-cells in the peripheral blood
      and lymph nodes of melanoma patients.
AB  - T-cell activation by malignant melanoma would be anticipated to stimulate T-cell
      proliferation, which in turn has been associated with increasing the likelihood
      of somatic gene mutation. The purpose of this study was to test the hypothesis
      that in vivo hypoxanthine guanine phosphoribosyltransferase (hprt) mutant
      frequencies (MFs) are increased in peripheral blood T-cells from melanoma
      patients compared to normal controls. Assays were made of 48 peripheral blood
      samples from melanoma patients with stage 3 (13 patients) and stage 4 (35
      patients) disease, 38 normal controls, and of nine tumor bearing lymph nodes. The
      mean hprt log(10)(MF) in patient peripheral blood was -4.77 (geometric mean hprt
      MF=17.0x10(-6)) compared to a mean hprt log(10)(MF) of -4.87 (geometric mean hprt
      MF=13.5x10(-6)) in controls. Although modest, this difference is statistically
      significant both by t-test (P=0.049) and after adjustment for covariates of age,
      gender, and cigarette smoking by regression analysis (P=0.001). Among the
      melanoma patients, the mean log(10)(MF) for the 17 patients who had received
      potentially genotoxic therapies was not significantly different from the mean
      log(10)(MF) for the 31 patients not receiving such therapies. The hprt MFs in the
      nine tumor bearing nodes were compared with MFs in peripheral blood from the same
      patients and revealed a non-significant (P=0.07) trend for increasing MFs in
      blood. Furthermore, analyses of T-cell receptor gene rearrangement patterns
      revealed hprt mutants originating from the same in vivo clone in both peripheral
      blood and a tumor-bearing node. The finding of elevated hprt MFs not entirely
      explained by genotoxic therapies in patients compared to controls can be
      explained either by hypermutability or in vivo T-cell activation. The similar MFs
      in peripheral blood and tumor bearing lymph nodes, as well as the finding of
      mutant representatives of the same in vivo T-cell clone in both locations,
      support monitoring peripheral blood to detect events in the nodes. If in vivo
      proliferation accounts for the current findings, the hprt deficient (hprt-)
      mutant fraction in blood may be enriched for T-cells that mediate the host immune
      response against malignant melanoma. Further studies will characterize the
      functional reactivity of hprt mutant isolates against melanoma-related antigens.

PMID- 11336987
TI  - Mutations induced by 5-formyl-2'-deoxyuridine in Escherichia coli include base
      substitutions that can arise from mispairs of 5-formyluracil with guanine,
      cytosine and thymine.
AB  - 5-Formyluracil (5-foU) is a major oxidation product of thymine formed in yields
      comparable to that of 8-oxoguanine in DNA by ionizing radiation. Whereas the
      mutagenic effects of 8-oxoguanine are well understood, the investigation of the
      biological implications of 5-foU has so far been limited. Here we demonstrate
      that 5-formyl-2'-deoxyuridine (5-fodUrd) supplied to the growth medium of
      Escherichia coli induces several base substitutions at different frequencies at
      position 461 in the lacZ gene in the following order: A.T-->G.C>G.C-->A.T>G.C-
      >T.A>>A.T-->T.A>A.T-->C.G. No induction of G.C-->C.G transversions was observed.
      It is inferred that 5-fodUrd will be incorporated into the DNA during cell
      growth, forming mispairs with guanine, cytosine and thymine during replication.
      It, thus, appears that cell growth in the presence of 5-fodUrd may represent a
      good model for elucidating the cellular effects of 5-foU residues in DNA.

PMID- 11336988
TI  - Evaluation of the effect of 90Sr beta-radiation on human blood cells by
      chromosome aberration and single cell gel electrophoresis (comet assay) analysis.
AB  - Among various environmental genotoxins, ionizing radiation has received special
      attention because of its mutagenic, carcinogenic and teratogenic potential. In
      this context and considering the scarcity of literature data, the objective of
      the present study was to evaluate the effect of 90Sr beta-radiation on human
      cells. Blood cells from five healthy donors were irradiated in vitro with doses
      of 0.2-5.0Gy from a 90Sr source (0.2Gy/min) and processed for chromosome
      aberration analysis and for comet assay. The cytogenetic results showed that the
      most frequently found aberration types were acentric fragments, double minutes
      and dicentrics. The alpha and beta coefficients of the linear-quadratic model,
      that best fitted the data obtained, showed that 90Sr beta-radiation was less
      efficient in inducing chromosome aberrations than other types of low linear
      energy transfer (LET) radiation such as 3H beta-particles, 60Co gamma-rays, 137Cs
      and 192Ir and X-rays. Apparently, 90Sr beta-radiation in the dose range
      investigated had no effect on the modal chromosome number of irradiated cells or
      on cell cycle kinetics. Concerning the comet assay, there was an increase in DNA
      migration as a function of radiation dose as evaluated by an image analysis
      system (tail moment) or by visual classification (DNA damage). The dose-response
      relation adequately fitted the non-linear regression model. In contrast to the
      cytogenetic data, 90Sr beta-radiation induced more DNA damage than 60Co gamma
      radiation when the material was analyzed immediately after exposures. A possible
      influence of selective death of cells damaged by radiation was suggested.

PMID- 11336989
TI  - Possible role of natural killer cells in negative selection of mutant lymphocytes
      that fail to express the human leukocyte antigen-A2 allele.
AB  - Increased frequencies of cells carrying mutations at several loci have been found
      in the blood cells of atomic-bomb (A-bomb) survivors upon testing four or five
      decades after the bombing. Interestingly, though, we have been unable to
      demonstrate any radiation-associated increases in the frequencies of mutant blood
      cells in which human leukocyte antigen (HLA)-A expression has been disrupted;
      this is true both of preliminary tests on the T cells of a small subset of A-bomb
      survivors and of the much more extensive study reported here in which we screened
      a much larger group of survivors for HLA-A2 loss mutations in B cells and
      granulocytes as well as in T cells. In attempting to explain our inability to
      detect any increases in HLA-A2-negative cell numbers in HLA-A2 heterozygous
      individuals exposed to A-bomb irradiation, we decided to test the hypothesis that
      HLA-A mutant lymphocytes might well have been induced by radiation exposure in
      much the same way as every other type of mutant we encountered, but may
      subsequently have been eliminated by the strong negative selection associated
      with their almost inevitable exposure to autologous natural killer (NK) cells in
      the bloodstream of each of the individuals concerned. We now report that mutant B
      lymphocyte cell lines that have lost the ability to express the HLA-A2 antigen do
      indeed appear to be much more readily eliminated than their parental heterozygous
      counterparts during co-culture in vitro with autologous NK cells. We make this
      claim first because we have observed that adding autologous NK cells to in vitro
      cultures of HLA-A2 heterozygous B or T cell lines appeared to cause a dose
      dependent decrease in the numbers of HLA-A2-negative mutants that could be
      detected over a period of 3 days, and second because when we used peripheral
      blood HLA-A2 heterozygous lymphocyte cultures from which most of the autologous
      NK cells had been removed we found that we were able to detect newly-arising HLA
      A2 mutant T cells in substantial numbers. Taken together, these results strongly
      support the hypothesis that autologous NK cells are responsible for eliminating
      mutant lymphocytes that have lost the ability to express self-HLA class I
      molecules in vivo, and may well therefore explain why we have been unable to
      detect increased frequencies of HLA-A2 mutants in samples from any of the 164 A
      bomb survivors whose HLA-A2 heterozygote status made their lymphocytes suitable
      for our tests.

PMID- 11336990
TI  - SAR modeling of genotoxic phenomena: the effect of supplementation with
      physiological chemicals.
AB  - Structure-activity relationship (SAR) modeling of toxicological phenomena is
      optimal when the ratio of toxicants to non-toxicants included in the model is
      unity. Frequently, however, the experimental data available are enriched with
      toxicants, this appears to be especially true for genotoxicity data sets. It is
      demonstrated herein, using a Salmonella mutagenicity data set, that when there is
      a paucity of non-toxicants, the learning set may be augmented with physiological
      chemicals on the assumption that they are non-genotoxic.

PMID- 11336991
TI  - Meiotic stage-dependent induction of chromosome aberrations in Chinese hamster
      primary oocytes exposed to topoisomerase II inhibitor etoposide.
AB  - To investigate the chromosomal effects of topoisomerase II (topo-II)-interactive
      drugs on mammalian primary oocytes, female Chinese hamsters were treated with
      etoposide (VP-16) at various intervals pre- and post-human chorionic gonadotropin
      (hCG) injections. Chromosome analysis of oocytes at metaphase II (M II) showed
      that treatment with VP-16 at 50h pre-hCG had no effect, but the treatments
      between 24h pre-hCG and 2h post-hCG often caused structural chromosome
      aberrations. Although treatment at 4h post-hCG had no effect, subsequent
      treatments at 6 and 8h post-hCG produced a significant increase in structural
      chromosome aberrations. No effect was found following treatment at 10h post-hCG.
      The incidence of aneuploidy following exposure to VP-16 was also dependent on the
      time of hCG injection. Taking the time course of meiotic progression in primary
      oocytes following hCG injection and pharmacokinetics of VP-16 into consideration,
      it is likely that meiotic stages from late dictyate to diakinesis are highly
      sensitive to VP-16, while stages at dictyate and from metaphase I (M I) to
      telophase I (telo I) are relatively insensitive to the drug. Moreover, the effect
      of VP-16 on structural chromosome aberrations and aneuploidy was dose-dependent.
      Chromosome analysis at M I detected a frequent occurrence of structural
      chromosome aberrations in treated oocytes. This suggests that structural
      aberrations may be caused by disruption of cleavable complexes during chromosome
      condensation. Detection of chromosome bridges during anaphase I/telophase I (ana
      I/telo I) may support the hypothesis that induction of aneuploidy by VP-16 is due
      to failure in decatenation of recombinant homologous chromosomes.

PMID- 11336992
TI  - Phenotypes of Drosophila homologs of human XPF and XPG to chemically-induced DNA
      modifications.
AB  - DmXPF (mei9) and DmXPG (mus201) mutants are Drosophila homologs of the mammalian
      XPF and XPG genes, respectively. For Drosophila germ cells, causal correlations
      exist between the magnitude of a potentiating effect of a deficiency in these
      functions, measured as the M(NER-)/M(NER+) mutability ratio, and the type of DNA
      modification. M(NER-)/M(NER+) mutability ratios may vary with time interval
      between DNA adduct formation and repair, mutagen dose and depend also on the
      genetic endpoint measured. For forward mutations, there is no indication of any
      differential response of DmXPF compared to DmXPG. Subtle features appeared from a
      class-by-class comparison: (i) Methylating agents always produce higher M(NER
      )/M(NER+) ratios than their ethylating analogs; (ii) M(NER-)/M(NER+) mutability
      ratios are significantly enhanced for cross-linking N-mustards, aziridine and di
      epoxide compounds, but not for cross-linking nitrosoureas. The low
      hypermutability effects with bifunctional nitrogen mustards, aziridine and
      epoxide compounds are attributed to unrepaired mono-alkyl adducts; (iii) The
      efficient repair of mono-alkyl-adducts at ring nitrogens in wild-type germ cells
      is evident from the absence of a dose-response relationship for ethylene oxide,
      propylene imine and methyl methanesulfonate (MMS). These chemicals become
      powerful germline mutagens when the NER system is disrupted. Systematic studies
      of the type performed on germ cells are not available for somatic cells of
      Drosophila. The sparse data available show large differences in the response of
      germ cells and somatic cells. The bifunctional agent mechlorethamine (MEC) but
      not the monofunctional MMS or 2-chloroethylamine cause in NER(-) XXfemale symbol
      the highest potentiating effect on mitotic recombination. The causes of the
      discrepancy between the extraordinarily high activity of MEC in mus201 somatic
      cells and its low potentiating effect in germ cells is unknown at present.

PMID- 11336993
TI  - Food intake inhibition by melatonin in goldfish (Carassius auratus).
AB  - Feeding regulation by monoamines, neuropeptides and certain hormones has been
      studied in fish, but a possible role of melatonin is unknown. The purpose of the
      present study was to investigate the effects of melatonin on food intake in
      goldfish. Fishes were housed in 12L:12D and injected with different doses of
      either melatonin or 2-iodomelatonin. Two routes of administration,
      intracerebroventricular and intraperitoneal injections, and two times of the
      daily photocycle, midday and midnight, were tested. Food intake was measured at
      2, 5 and 8 h postinjection. Melatonin and its analog, 2-iodomelatonin
      intracerebroventricularly injected had no effect on food intake at any time.
      However, intraperitoneal injections of both indoleamines significantly reduced
      food intake at different postinjection times. The inhibitory effect of melatonin
      was blocked by intraperitoneal administration of its antagonist, luzindole. These
      results demonstrate the in vivo efficiency of luzindole as melatonin antagonist,
      and thus provide a useful experimental tool to investigate melatonin functions.
      In conclusion, both melatonin and its agonist 2-iodomelatonin administered
      peripherally, inhibit food intake in goldfish, and this inhibitory effect appears
      to be mediated via luzindole-sensitive melatonin receptors. Our results strongly
      suggest that melatonin is involved in the peripheral satiety mechanisms in
      goldfish.

PMID- 11336994
TI  - Defense changes in stress nonresponsive subordinate males in a visible burrow
      system.
AB  - Dominant and subordinate male rats housed in a visible burrow system (VBS), and
      male controls each housed with a female, were run in a series of tests evaluating
      their response to threatening stimuli. Subordinates were later assessed as stress
      responsive (SRS) or nonresponsive (NRS) on the basis of plasma corticosterone
      response to restraint stress. In the tests using mildly threatening stimuli
      (handling, open field), NRS had longer latencies to show a righting response and
      reduced activity compared to SRS or (handling, open field) to dominants. There
      were no differences among the VBS groups in tests with more intense threat
      stimuli (cat odor, cat presentation). These results suggest that stressful social
      experience may produce a shift toward more passive and immobile forms of defense
      and that the experience of subordination may interact with individual differences
      characteristics of rats to exacerbate this shift. The hypothalamic-pituitary
      adrenal (HPA) axis changes of NRS, manifested as reduced plasma corticosterone
      response to restraint, and previous findings of sharply reduced testosterone in
      these animals, along with their passive defensive behaviors, form a pattern that
      is suggestive of a biobehavioral "reactive" (as opposed to "proactive") coping
      style, and suggest that these behavioral and endocrine variables may show related
      changes even when altered by individual experience.

PMID- 11336995
TI  - Are memories for stimulus-stimulus associations or stimulus-response associations
      responsible for serial-pattern learning in rats?
AB  - Previous research has provided convincing evidence that rats can learn to
      anticipate the individual elements of a stimulus series consisting of differing
      amounts of food reinforcement. Rats prepared with lesions of the dorsal striatum
      or hippocampus were initially trained to acquire a three-element series
      consisting of 21 sucrose pellets, followed by 0- and 7-pellets (Noyes standard),
      respectively. During the initial 30 days of training, the animals were run in two
      adjacent runways; the runways included either of a white, rough runway or a
      black, smooth runway as additional series cues. Thus, training included both
      floor (S-R) cues and the series (inter-item memory) cues. Anticipation was
      defined as faster running on the 21- than on the 7-pellet element and 7- than on
      the 0-pellet element. While anticipation developed more slowly in the lesion
      groups than in the control group, all animals eventually demonstrated the ability
      to track the elements of the series. Reversal of the floor cues disrupted
      tracking in the hippocampus-lesioned and control animals; dorsal striatum
      lesioned rats were also affected but did continue tracking. As a final test,
      shifting the order of the series produced a marked disruption in performance in
      the dorsal striatum-lesioned rats but not in the hippocampus-lesioned or control
      rats. The results are consistent with the proposal that integrated neural
      mediation is required for anticipation, with a system that includes the dorsal
      striatum necessary for the promotion of a reinforced approach response and a
      system that includes the hippocampus necessary for associating and temporarily
      maintaining an internal record of the different elements of the stimulus series.

PMID- 11336996
TI  - Evidence that age-induced decline in memory retention is delayed in growth
      hormone resistant GH-R-KO (Laron) mice.
AB  - Although the role of growth hormone (GH) in aging is controversial, the recent
      production of GH-R-KO mice may provide a means for elucidating its importance.
      Using the inhibitory avoidance learning task as a measure of cognitive aging, the
      present study compared learning and retention in young and old GH-R-KO mice and
      their normal siblings. Results for the old normal animals agreed with the current
      literature, in that the ability of old animals to retain learned information
      declined over time. However, retention in the old GH-R-KO mice did not decline
      between the 24-h, 7-day and 28-day retention tests and did not differ from young
      animals. To determine whether performance differences seen in the old normal vs.
      old GH-R-KO groups were due to locomotor behavior or emotionality, both groups
      were tested in the elevated-plus maze. Results showed that the normal and GH-R-KO
      mice did not differ in number of open or closed arms entered, time spent in
      closed or open arms or time taken to first enter an open arm. Thus, it was
      concluded that inhibitory avoidance performance was not affected by differences
      of locomotor activity or emotionality, and that the absence of GH signaling may
      be associated with improved long-term memory in aging mice.

PMID- 11336997
TI  - Factors that influence the persistence of stimulation-induced aversion.
AB  - Brain stimulation reward in certain regions has been shown to produce analgesia
      to externally applied painful stimuli. In the present experiments, we studied how
      electrical self-stimulation of the dorsal raphe (DR) nucleus modifies the
      aversive effects of electrical stimulation of the nucleus reticularis
      gigantocellularis (Gi) or of the dorsal tegmentum (DTg). In the first study, the
      threshold for latency to escape aversive Gi stimulation was tracked before and
      after exposure to rewarding DR stimulation. Only a few sessions of DR self
      stimulation were required to produce a complete and long-lasting inhibition of Gi
      aversion. In the second study, the aversion induced by DTg stimulation rapidly
      disappeared following a few test sessions at that site. Unlike our previous
      experience with Gi aversion that required either pairing with rewarding lateral
      hypothalamic (LH) or ventral tegmental area (VTA) pulses in order to increase the
      threshold for latency to escape Gi aversion, in this study, simply brief
      experience with rewarding DR stimulation in unpaired trials was sufficient to
      entirely suppress Gi-induced aversion. Even more surprising was the finding that
      unlike the Gi, aversion obtained from activation of the DTg does not persist, its
      threshold for escape quickly increases, and within a few sessions is no longer
      evident. One interpretation of these findings is that the aversion mechanisms
      associated with the Gi and DTg are differentially susceptible to analgesic
      processes.

PMID- 11336998
TI  - Behavioral and hormonal responses to corticosterone in the male red-sided garter
      snake, Thamnophis sirtalis parietalis.
AB  - Stress and glucocorticoids are generally thought to suppress reproductive
      function at multiple levels. We tested the hypotheses that exogenous
      corticosterone would suppress sexual behavior in a dose-dependent manner, as well
      as drive a decrease in plasma testosterone levels in the male red-sided garter
      snake, Thamnophis sirtalis parietalis. We examined this by challenging individual
      males with intraperitoneal injections of exogenous corticosterone, and
      subsequently exposing them to sexually attractive females or taking a blood
      sample. Previous work has demonstrated a hormonal but no behavioral response to
      stress in this species. In this study, increasing concentrations of exogenous
      corticosterone rapidly suppressed mating behavior in a threshold manner. However,
      exogenous corticosterone had no effect on plasma levels of testosterone. Thus,
      these data suggest that the mechanism is in place for corticosterone to suppress
      mating behavior in this species and that these effects do not occur because of an
      indirect effect on plasma levels of testosterone but rather are the direct effect
      of the hormone itself. In addition, the negative relationship observed previously
      between plasma levels of corticosterone and testosterone in this species was
      probably not the direct result of corticosterone acting on the hypothalamic
      pituitary-gonadal (HPG) axis. Rather, our results seem to indicate that the
      negative associations between the hypothalamic-pituitary-adrenal axis (HPA) and
      the HPG axis occur at other levels of these neuroendocrine pathways.

PMID- 11336999
TI  - Modulation of aggression in male mice: influence of group size and cage size.
AB  - Aggression in group-housed male mice is known to be influenced by both cage size
      and group size. However, the interdependency of these two parameters has not been
      studied yet. In this study, the level of aggression in groups of three, five, or
      eight male BALB/c mice housed in cages with a floor size of either 80 or 125
      cm(2)/animal was estimated weekly after cage cleaning for a period of 14 weeks.
      Furthermore, urine corticosterone levels, food and water intake, body weight, and
      number of wounds were measured weekly. At the end of the experiment, tyrosine
      hydroxylase (TH) activity, testosterone levels, and weight of spleen, thymus,
      testes, and seminal vesicles were determined. Results indicate a moderate
      increase of intermale aggression in larger cages when compared to the smaller
      cages. Aggression in groups of eight animals was considerably higher than in
      groups of three animals. The increase of agonistic behavior was observed both in
      dominant and subordinate animals. Physiological parameters indicate differences
      in stress levels between dominant and subordinate animals. It is concluded that
      aggressive behavior in group-housed male BALB/c mice is best prevented by housing
      the animals in small groups of three to five animals, while decreasing floor size
      per animal may be used as a temporary solution to decrease high levels of
      aggression in an existing social group.

PMID- 11337000
TI  - Effect of lysine on afferent activity of the hepatic branch of the vagus nerve in
      normal and L-lysine-deficient rats.
AB  - Amino acid deficiency was modeled by feeding rats a diet deficient in the
      essential L-amino acid, L-lysine (L-lys). There is a rapid anorectic response to
      such a diet, and a strong preference for L-lys develops during the deficiency.
      While the brain appears to trigger this preference, the peripheral pathways that
      inform the brain about the deficiency are not well understood. One possible
      information pathway may utilize an "amino acid sensor" in the hepatoportal
      region. In the present study, we measured in vivo neural activity in normal and L
      lys-deficient rat. Compared to the normally fed controls, we found an
      approximately 100-fold increase in the firing sensitivity of the L-lys sensors in
      vagal afferent fibers from the hepatoportal region of the L-lys-deficient rats.
      Injection of 10 mM L-lys into the hepatoportal circulation, but not D-lysine (D
      lys), evoked an increase in afferent activity. While L-lys deficiency enhanced
      the sensitivity of the L-lys sensors, the sensitivity due to other small amino
      acid sensors remained unchanged. Finally, we observed a time-dependent response
      of the lysine sensors to lysine deficiency. It required 3-4 days of maintenance
      on the lysine-deficient diet for the sensitivity of the L-lys sensors to change.
      Taken together, these results provide additional data to support the existence of
      putative L-amino acid sensors in the hepatoportal circulation. Additionally, they
      describe several characteristics of the L-lys sensors and show that these sensors
      may contribute to the adaptation to dietary L-lys deficiency and to maintenance
      of L-amino acid homeostasis.

PMID- 11337001
TI  - Flavor preferences conditioned by intragastric fructose and glucose: differences
      in reinforcement potency.
AB  - Many prior conditioning studies indicate that fructose, unlike glucose, has
      minimal postingestive reinforcing effects. Using a new training procedure, food
      restricted rats were trained in alternate 20-h/day sessions with one flavored
      solution (CS+F) paired with intragastric (IG) infusions of 16% fructose and
      another flavor (CS-) paired with IG water. In subsequent two-bottle tests they
      showed a robust (85%) preference for the CS+F over the CS-. A third flavor (CS+G)
      was then paired with IG 16% glucose, and it was strongly preferred to the CS+F.
      When retrained 30 min/day with new flavors paired with IG fructose, glucose, or
      water the rats learned only a CS+G preference. When training was extended to 20
      h/day, a CS+F preference developed. New rats trained 20 h/day with two-bottle
      access to CS+F and CS- paired with IG fructose and water failed to acquire a CS+F
      preference. Other rats rapidly developed a strong preference when trained with
      concurrent access to CS+G and CS- paired with IG glucose and water. These data
      indicate that both fructose and glucose generate postingestive reinforcing
      signals, but that the fructose signals are weaker and/or delayed relative to
      those produced by glucose.

PMID- 11337002
TI  - Odorant exposure increases olfactory sensitivity: olfactory epithelium is
      implicated.
AB  - Exposure-induced shifts in sensitivity to odors may involve peripheral and/or
      central components of the olfactory system. The ability to disconnect the
      olfactory epithelium from the bulbs provides a unique opportunity to examine how
      odorant exposure affects each component. In one experiment, odor thresholds were
      established for either amyl acetate or androstenone. The mice were then exposed
      for 10 days to the same test odorant for which a threshold was obtained. After
      exposure, sensitivity to the odorant increased relative to preexposure levels.
      The mice then underwent bilateral olfactory nerve transection (BNX). When both
      groups of mice were tested 45-50 days after recovery from surgery and return of
      olfactory function, increased sensitivity to the exposed odorant persisted;
      however, 121-203 days after surgery, sensitivity returned to preexposure levels.
      Another experiment was similar to the first except that mice were exposed to an
      odorant, either amyl acetate or androstenone, for 10 days beginning 1 day after
      BNX or sham surgery. When the mice were tested 45-50 days after surgery,
      sensitivity to the exposed odorant was increased relative to preexposure levels,
      whereas sensitivity to the nonexposed odorant remained at preexposure levels.
      Although further work is needed to determine the precise mechanism(s) underlying
      shifts in sensitivity to odors, these studies provide additional evidence for
      peripheral involvement in exposure-induced sensitization to odorants and
      demonstrate the remarkable capacity of the olfactory system to maintain or even
      regain sensitivity after injury.

PMID- 11337003
TI  - Prolactin levels are elevated after infant carrying in parentally inexperienced
      common marmosets.
AB  - Alloparental behavior (parental behavior directed to nondescendant young) is
      pervasive among human cultures but rare among other mammals. New World primates
      of the family Callitrichidae, including common marmosets (Callithrix jacchus
      jacchus), dwell in large families and many family members carry and/or provision
      infants. This study experimentally characterized alloparenting in common
      marmosets by measuring infant retrieval and carrying outside of the context of
      the family group. Prolactin was measured in samples collected before and after
      infant exposure to determine whether elevated prolactin levels were predictive of
      alloparental responsiveness. Seventeen nonbreeding, parentally inexperienced,
      singly or peer-housed common marmosets (10 females, 7 males, 6-66 months of age)
      were tested repeatedly in an infant retrieval paradigm. Infant retrieval was
      shown by 5 out of 17 monkeys (29%) in their first test. The rate of retrieval
      increased to 10 monkeys (59%) by the fourth test. No significant differences in
      age, sex, or housing condition existed between monkeys that retrieved infants and
      those not retrieving. Prolactin concentrations were significantly elevated in
      serum obtained after testing only in monkeys that retrieved infants. Prolactin
      levels after infant exposure were positively related to carrying duration. A
      separate experiment verified that neither prolactin nor cortisol was
      significantly elevated in response to prolonged handling. Cortisol levels were
      inversely proportional to handling time. Prolactin levels were not significantly
      related to handling time. Our results indicate that alloparental behavior is
      expressed at high rates after minimal infant experience, and prolactin levels
      rise concomitantly with the expression of alloparental behavior in this species.

PMID- 11337004
TI  - Feeding behavior during sialodacryoadenitis viral infection in rats.
AB  - Sialodacryoadenitis (SDA) is a highly contagious common viral infection in rats,
      akin to mumps in humans. Anorexia occurs during such viral infection. But the
      pattern of the decrease in food intake (a decrease in either meal size and meal
      number or both) during spontaneous viral infection has not been previously
      characterized. We observed the onset of anorexia and an abnormal feeding pattern
      during an opportunistic SDA viral infection in our rat colony. We thus studied
      seven male rats. Before the viral infection there was a positive association
      between food intake and meal number (P<.05). After infection food intake
      decreased by 68%. This occurred via a significant decrease in meal size (by 69%)
      (P<.05); and a nonsignificant decrease in meal number (P=.71). This pattern of
      decreased food intake is similar to that occurring during indomethacin-induced
      ulcerative ileitis, where we previously measured an increase in plasma tumor
      necrosis factor (TNF)-alpha. Anorexia in response to bacterial lipopolysaccharide
      administration, which is also linked to plasma TNF-alpha, is however, caused only
      via a decrease in meal number. The differences in the decrease in the feeding
      pattern between the SDA viral and a bacterial infection suggest that factors
      other than TNF-alpha alone play a significant role in the mechanism of anorexia
      during a viral infection.

PMID- 11337005
TI  - Steroidal control of male hamster sexual behavior in Me and MPOA: effects of
      androgen dose and tamoxifen.
AB  - Steroids stimulate male sexual behavior through interconnected limbic nuclei,
      including the medial amygdala (Me) and medial preoptic area (MPOA). Although Me
      and MPOA each can transduce hormonal cues to induce sexual activity in castrated
      male hamsters, simultaneous stimulation of Me and MPOA fails to amplify mating.
      The present study extends our investigations of redundancy in the hormonal
      control of mating by testing the behavioral effects of (1) increasing steroid
      dose in a single brain region or (2) locally blocking steroid action with an
      estrogen antagonist. In Experiment 1, sexually experienced castrates received a
      single testosterone implant in Me, bilateral testosterone implants, or a single
      implant of a highly potent androgen, 7a-methyl-19-nortestosterone (MENT). These
      treatments stimulated mating behavior: 2 weeks after surgery, mounting was
      observed in > or =50% of the males in each group. In Experiment 2, castrated
      males received intracerebral implants of the estrogen antagonist tamoxifen in Me
      or MPOA, combined with systemic testosterone replacement. Tamoxifen in MPOA had
      minimal effects on the recovery of mating behavior. With tamoxifen in Me, mounts
      and intromissions were significantly reduced 18 days after surgery. However, the
      percent of males in each group that expressed mounts, intromissions or
      ejaculations was not different. Thus, in Experiment 1, increasing the amount of
      steroid does not amplify mating. Likewise, local blockade of hormone action in
      Experiment 2 does not prevent behavior. These findings support the concept that
      steroids are largely permissive for male sex behavior. Steroid stimulation of
      either Me or MPOA is sufficient for sexual activity. Conversely, neither Me nor
      MPOA has an absolute requirement for hormones to facilitate expression of mating.

PMID- 11337006
TI  - Effects of amygdala lesions on body weight, conditioned taste aversion, and
      neophobia.
AB  - Female rats with posterodorsal amygdala (PDA), basolateral amygdala (BLA), or
      sham lesions were compared regarding ad libitum food intake, weight gain,
      consumption of a novel food, and acquisition of a conditioned taste aversion
      (CTA). While only the rats with PDA lesions evidenced substantial weight gains at
      10 days after surgery eating standard lab chow (25-45 g more than the other
      groups), only the rats with BLA lesions demonstrated significant deficits in the
      CTA and neophobia paradigms. Rats with basolateral lesions, on average, took less
      than 30 s to begin drinking the novel sweetened condensed milk after pairing with
      illness while the other groups took approximately 15 min to begin drinking. Also,
      rats with basolateral lesions ate, on average, 5 g of the novel Froot Loops while
      the other groups ate approximately 2 g. It is concluded that the changes in food
      motivated behavioral tests frequently observed in animals with amygdala lesions
      do not coexist with the hyperphagia and weight gain of animals with PDA lesions.

PMID- 11337007
TI  - Altered NaCl taste responses precede increased NaCl ingestion during Na(+)
      deprivation.
AB  - It has been suggested that Na(+) deficiency alters the sensitivity of taste
      receptors, thereby rendering NaCl solutions more palatable or preferred and more
      likely to be ingested. Increased ingestion of concentrated NaCl solutions by rats
      during dietary Na(+) deprivation occurs only after approximately 8-10 days. To
      determine whether changes in gustatory responses mediate the deprivation-induced
      NaCl ingestion (salt appetite), we evaluated taste responses to a range of NaCl
      concentrations before, during, and after dietary Na(+) deprivation. Rats were
      trained to lick rapidly in short-duration (10 s) tests by mixing NaCl solutions
      in a dilute sucrose solution. This method elicited consistent, interpretable
      rates of licking, even of normally avoided NaCl concentrations, without the
      necessity of depriving the rats of water. The licking rate increased after
      dietary Na(+) deprivation of only 2 days, increased further after 5 days of Na(+)
      deprivation and, after 10 days, was not different from that after 2 days. These
      results suggest that a change in the response to NaCl taste, as evidenced by
      increased rates of licking during short-access tests, occurred after 2 days of
      dietary Na(+) deprivation. In contrast, a significant increase in the 24-h
      ingestion of a concentrated NaCl solution occurred only after approximately 1
      week of maintenance on Na(+)-deficient chow. Thus, it is unlikely that a delayed
      change in the response to NaCl taste to more palatable or preferred underlies the
      delayed increase in 24-h NaCl intake during dietary Na(+) deprivation.

PMID- 11337008
TI  - Retinoic acid down-regulates the expression of EmH-3 homeobox-containing gene in
      the freshwater sponge Ephydatia muelleri.
AB  - The effects of retinoic acid (RA), a common morphogen and gene expression
      regulator in vertebrates, were studied in the freshwater sponge Ephydatia
      muelleri, both on morphogenesis and on the expression of EmH-3 homeobox
      containing gene. At 0.3 microM, RA had no noticeable influence on sponge
      development, slightly up-regulating EmH-3 expression. In contrast, in sponges
      reared in 10, 8 microM and to a lesser extent 2 microM RA, there was a strong
      down-regulation of EmH-3 expression after hatching. This induced modifications in
      cell composition and morphology, greatly disturbing normal development.
      Archaeocytes kept the features found in newly hatched sponges while choanocytes
      and a functional aquiferous system were completely absent. The inhibition of
      morphogenesis and down-regulation of EmH-3 expression were reversible when
      sponges were no longer subjected to RA. After RA removal, EmH-3 expression
      returned to the high values found in untreated sponges, archaeocytes
      differentiated into choanocytes and sponges achieved a normal development. These
      results clearly show that, in freshwater sponges, the most primitive metazoan, RA
      may also act as a morphogen, regulating the expression of a homeobox-containing
      gene. They demonstrate that the expression of EmH-3 is necessary for the
      differentiation of archaeocytes into choanocytes and hence for the formation of a
      complete functional aquiferous system.

PMID- 11337009
TI  - Influence of treatment with Ca(2+) antagonists on cerebral vasculature of
      spontaneously hypertensive rats.
AB  - Hypertension is the main cause of stroke that represents the second most common
      cause of death in the industrialized world and a leading cause of inability of
      the elderly. Lowering blood pressure reduces cerebrovascular morbidity and
      mortality, but it is still controversial if blood pressure should be lowered in
      elderly individuals with concomitant cerebrovascular disease. The present study
      has analyzed comparatively the effect of treatment with the dihydropyridine-type
      Ca(2+) channel blockers lercanidipine, manidipine and nimodipine and with the non
      dihydropyridine-type vasodilator hydralazine on hypertension-dependent
      cerebrovascular changes in spontaneously hypertensive rats (SHR). Analysis
      included medium and small sized pial arteries and intracerebral arteries of
      frontal cortex, hippocampus, striatum, and cerebellum. In control SHR, systolic
      pressure (SBP) values were significantly higher in comparison with WKY rats.
      Pharmacological treatment significantly decreased SBP values, with nimodipine
      reducing only moderately SBP. In control SHR, thickening of arterial wall
      accompanied by luminal narrowing with consequent increase of the wall-to-lumen
      ratio occurred both in pial and intracerebral arteries. Dihydropyridine-type
      Ca(2+) antagonists and to a lesser extent hydralazine countered these
      morphological alterations. Lercanidipine displayed a particular activity on small
      sized intraparenchymal brain arteries, where it was more effective than other
      compounds tested. This activity of lercanidipine on small-sized intracerebral
      arteries might represent an interesting property for the treatment of
      hypertensive brain damage with concomitant ischemia.

PMID- 11337010
TI  - Enzyme activities in the light of the membrane hypothesis of aging. [An answer to
      K. Kitani, Mech. Ageing Dev. 107 (1999), 299-322].
AB  - The paper of Kitani cited in the title has raised an apparent contradiction
      regarding the validity of certain aspects of the membrane hypothesis of aging
      (MHA). He collected data showing that a number of detoxifying liver enzyme
      activities, although decline with age in male Fischer 344 rats, remain at an
      unchanged level in females of the same strain. He concluded that the main
      assumption of the MHA, according to which intracellular enzyme activities
      generally decline with age, cannot be maintained, and invoked me (p. 312)
      'ellipsis to provide in the future ample (and convincing) evidence' in this
      respect. The present paper answers this criticism by showing that the apparent
      contradiction mentioned above is based on a misunderstanding on behalf of Kitani.
      Namely, MHA speaks about the general, density-dependent decline of the catalytic
      rate constant of any enzyme (k(cat)), i.e., activity per mole of enzyme, being
      the true specific activity of the enzymes. This parameter inevitably decreases at
      the increased physical density of the intracellular colloids during aging. This
      statement derives from the molecular enzyme kinetic models, and has extensively
      been proven experimentally, too. On the other hand, Kitani speaks about enzyme
      activities per mg total protein content of certain tissue extracts, which is a
      very illdefined parameter, since the concentration of the measured enzyme remains
      unknown. Therefore, this latter parameter is irrelevant from the point of view of
      MHA in any aspect.

PMID- 11337011
TI  - Decreased Pasteur effect in platelets of aged individuals.
AB  - We have investigated the mitochondrial energy state in human platelets of young
      (19-30 years old) and aged individuals (65-87 years old) exploiting the Pasteur
      effect, i.e. stimulation of lactate production by incubation of the purified
      platelets with the mitochondrial respiratory chain inhibitor, antimycin A. This
      assay allows the determination of mitochondrial function with respect to
      glycolysis, and the ratio of mitochondrial adenosine triphosphate (ATP) to
      glycolytic ATP. A significant increase of basal, non-stimulated lactate
      production and decrease of the stimulation by antimycin A were observed in the
      older individuals, suggesting that the impairment of oxidative phosphorylation
      detectable in post-mitotic tissues of aged individuals can be observed also in
      easily collectable blood cells.

PMID- 11337012
TI  - Total antioxidant levels, gender, and age as risk factors for DNA damage in
      lymphocytes of the elderly.
AB  - During past years, the association of oxidative stress with DNA damage and its
      possible clinical translation into chronic degenerative illnesses, such as
      atherosclerosis, cancer, diabetes mellitus and Alzheimer's disease, has been
      demonstrated. In addition, it has been pointed out that age and gender are
      factors that influence the generation of DNA damage; however, this is still
      controversial. We have previously reported the results of a study of 88 subjects
      older than 60 years of age in whom DNA damage is related with serum levels of
      total antioxidants. The results of this study demonstrate a greater frequency of
      DNA damage in elderly persons with normal levels of antioxidants, in addition to
      males, and in the younger group of subjects, i.e., 60-69 years. In this work, we
      enlarged our study sample to 160 elderly subjects; in this way, we were able to
      evaluate the consistency of the influence of total antioxidants, age, and gender
      on the magnitude and grade of DNA damage in lymphocytes of the elderly. The
      results demonstrated that 45% of the subjects showed DNA damage, measured by an
      alkaline unicellular electrophoresis technique (comet assay). Similarly, 62% of
      the subjects presented low levels of total antioxidant levels measured by a
      colorimetric method (Randox Kit). A greater percentage of DNA damage was observed
      in subjects with normal levels of antioxidants (48%) compared with subjects with
      low levels (43%), although the difference was not statistically significant. The
      group of subjects 70 years of age or older showed a greater percentage of DNA
      damage (50%) than the group of subjects of 60-69 years of age (41%). However, the
      difference was again not statistically significant (P>0.05). With respect to
      gender, 64% of males and 38% of females had DNA damage with an odds ratio (OR) of
      2.86 and a 95% confidence interval (CI) of 1.31-6.32 (P<0.05). In the logistic
      regression analysis, the interaction of the male sex variables with low
      antioxidants had an OR of 2.5 (CI 95%, 1.33-4.68; P<0.01). We conclude that the
      interaction of male sex factors-low levels of antioxidants would justify the
      indication of antioxidant dietetic supplements.

PMID- 11337013
TI  - Analysis of the effects of growth hormone, exercise and food restriction on
      cancellous bone in different bone sites in middle-aged female rats.
AB  - The aim of this study is to determine the effects of growth hormone (GH),
      exercise (EX), GH+EX and food restriction on cancellous bone in middle-aged
      female rats. Female F344 rats aged 13 months were divided into (1) age-matched
      controls; (2) GH treated (2.5 mg/kg. 5 day/week); (3) EX (voluntary wheel
      running); (4) GH+EX; and (5) food restricted (FR) (fed 60% of the ad libitum food
      intake). The animals were treated for 18 weeks, at the end of which they were
      sacrificed. Cancellous bone and cortical bone in the fourth lumbar vertebra,
      proximal tibial metaphysis (PTM), distal femoral metaphysis (DFM) and femoral
      neck (NF) were analyzed using peripheral quantitative computerized tomography
      (pQCT) densitometry. Growth hormone increased cancellous bone area, cancellous
      bone mineral content, cortical bone area and cortical bone mineral content in the
      vertebra, PTM, DFM and NF. The tibial muscle wet weight was increased
      significantly after GH treatment. Exercise increased the cancellous bone area in
      the vertebra, PTM and DFM. Cortical bone area and cortical bone mineral content
      increased after EX in the vertebra, PTM, DFM and NF. No significant change was
      seen in the tibial muscle wet weight after EX. Growth hormone+EX increased
      cancellous bone area in the vertebra PTM and DFM but had no effect in neck of the
      femur. Cancellous bone mineral content, cortical bone area and cortical bone
      mineral content increased with GH+EX in the vertebra, PTM, DFM and NF. The tibial
      muscle wet weight was increased significantly with GH+EX. Food restriction
      decreased cancellous bone area and cancellous bone mineral content in all the
      bones studied. The decrease was statistically significant only at the distal
      femoral metaphysis. The tibial muscle wet weight decreased when compared with the
      age-matched control, but this decrease was not statistically significant. We
      conclude that the effect of the dose of GH used and the levels of voluntary wheel
      running EX used increased cancellous bone in intact rats; the effect of GH is
      much greater and different bones respond with varying intensities. The effects of
      combined treatment of GH and EX on cancellous bone are not always significantly
      higher than those of GH alone. FR at the level studied has a mostly negative
      effect on cancellous bone.

PMID- 11337014
TI  - Gemcitabine demonstrates in vitro activity against human B-cell chronic
      lymphocytic leukemia.
AB  - B-cell chronic lymphocytic leukemia (CLL) is the most common type of leukemia
      diagnosed in the Western Hemisphere and remains incurable with currently
      available therapy. In an attempt to identify new potential therapy for CLL, we
      explored the pre-clinical activity of gemcitabine in human B-CLL cells (n =11).
      Mononuclear cell isolates were exposed to varying concentrations of gemcitabine
      (0.01-100 microM) for 4, 24, and 96 h. Viability, as determined by the
      tetrazolium salt (MTT) assay, after a 4 h incubation with gemcitabine declined in
      6 of 8 (75%) evaluable patients at a concentration < 30 microM (a physiologically
      attainable level), and 3 of 8 of the B-CLL cells had an LC50 (concentration where
      50% loss of viability is observed) < 30 microM. At 4 days of drug exposure, 82%
      (9/11) of patients had an LC50 < 30 microM. Annexin-V/propidium iodine staining
      demonstrated apoptosis in CLL cells exposed to 30 microM of gemcitabine.
      Examination of changes in apoptosis related proteins demonstrated no significant
      change in bcl-2, bax or p53 protein expression with gemcitabine (23 microM) at 4,
      24, or 48 h. These data demonstrate that gemcitabine has pre-clinical activity in
      B-CLL and supports its exploration as a single agent and in combination with
      other active agents in this disease.

PMID- 11337015
TI  - Loss of p73 gene expression in lymphoid leukemia cell lines is associated with
      hypermethylation.
AB  - The expression of the p73 gene and the methylation status was examined in 61
      acute lymphoblastic leukemia (ALL) cell lines and lymphocytes from seven healthy
      individuals. p73 mRNA was not expressed in 19 (31.1%) of 61 ALL cell lines,
      including 11 (31.4%) of 35 B-precursor ALL cell lines, 2 (16.7%) of 12 B
      ALL/Burkitt lymphoma (BL) cell lines (totally 27.7% of B-lineage cell lines), 6
      (42.9%) of 14 T-ALL cell lines, and expressed in all of normal lymphocytes, by
      reverse transcriptase-polymerase chain reaction (RT-PCR). Restriction-enzyme
      related PCR (REP) and methylation-specific PCR (MSP) revealed that the cell lines
      lacking p73 mRNA expression were hypermethylated. In contrast, normal lymphocytes
      and most cell lines that expressed detectable p73 mRNA were not hypermethylated
      with the exception of five cell lines. Furthermore, bisulfite genomic sequencing
      confirmed the results obtained by REP and MSP. Our results suggest that p73
      inactivation may be involved in the pathogenesis of both T- and B-ALLs, and that
      hypermethylation is the predominant mechanism of inactivation of the p73 gene in
      ALL.

PMID- 11337016
TI  - Labdane type diterpenes down-regulate the expression of c-Myc protein, but not of
      Bcl-2, in human leukemia T-cells undergoing apoptosis.
AB  - Sclareol (1) and ent-3beta-hydroxy-13-epi-manoyl oxide (2) belong to the labdane
      type diterpenes. They were isolated from the leaves and from the fruits of Cistus
      creticus subsp. creticus, and were found to be active against human leukemic cell
      lines. Compound 2 was converted to its thiomidazolide derivative (3). Compounds 1
      and 3 were found to induce apoptotic cell death in human T-cell leukemia lines
      and to interfere with their cell cycle, arresting cells at G(0/1) phase.
      Apoptosis can involve the activation and/or suppression of critical genes such as
      c-myc whose reduction or its inappropriate expression can be associated with
      induction of cell death and bcl-2 whose activation prevents apoptosis in the
      latter case. In order to detect any concomitant effect (1 and 3) upon c-myc and
      bcl-2 oncogene expression, we performed Western blot analysis to determine the
      levels of expression of these two genes upon treatment with the above compounds.
      Western blot analysis showed that of c-myc proto-oncogene levels were markedly
      reduced before massive apoptosis ensued in H33AJ-JA1 and MOLT3 cells, while bcl-2
      expression remained unaffected. Thus, induction of apoptosis due to compounds 1
      and 3 in these T-cell leukemic cell lines is preceded by c-myc down regulation
      and furthermore sustained bcl-2 expression does not rescue cells from apoptosis
      under the conditions used.

PMID- 11337017
TI  - The effects and mechanisms of a novel 2-aminosteroid on murine WEHI-3B leukemia
      cells in vitro and in vivo.
AB  - To evaluate the effects of a novel 2-aminosteroid, 2-(4'-methyl-1'-piperazinyl)
      3alpha-hydroxyl-5alpha-androstane-17-one (KH), on in vitro murine WEHI-3B
      leukemia cells, semisolid colony culture, MTT assay, morphological examination,
      NBT reduction, NSAE test and ACP assay were used to determine proliferation and
      differentiation. It was found that the growth of leukemia cells in colony and
      liquid cultures was inhibited by KH (10(-8)-10(-4) mol/l) after treatment for 7
      days. The percentages of NBT and NSAE positive cells were 71.17 and 79.25%,
      respectively, after treatment with KH (10(-8)-10(-6) mol/l) for 5 days. The
      morphology of treated leukemia cells was identified to be macrophage-like and
      these cells acquired significant ACP activities. It was indicated that the ACP
      enzyme activities were increased as high as two and three times of the control,
      respectively, after treatment with 10(-8) or 10(-5) mol/l KH for 6 days. It was
      also indicated by DNA fragmentation in gel electrophoresis that WEHI-3B cells
      were induced toward apoptosis by KH (10(-8)-10(-4) mol/l) when checked at day 5.
      The c-myc mRNA expressions in WEHI-3B cells were decreased by 58.7% after
      treatment with KH (10(-8) mol/l) for 5 days. Therefore, it is first reported here
      that KH, a novel 2-aminosteroid, could suppress proliferation and induce
      differentiation of WEHI-3B leukemia cells. These differentiated cells were mature
      macrophage-like cells and showed characteristics of functional phagocytes
      acquired with acid phosphatase activity. The mechanisms underlying the above
      effects involved the apoptosis of WEHI-3B leukemia cells and the down-regulation
      of c-myc oncogene expression. It is also shown that the counts of immature
      granulocytes and monocytes were significantly decreased in both peripheral blood
      and bone marrow of BALB/c leukemia mice after KH was administrated per os for 7
      consecutive days with four doses (5, 10, 15 or 20 mg/kg day), respectively. It is
      also observed that the enlarged spleens in leukemia mice were decreased when
      compared with the control.

PMID- 11337018
TI  - STAT3 exerts two-way regulation in the biological effects of IL-6 in M1 leukemia
      cells.
AB  - The signal transducer and activator of transcription (STAT) proteins have been
      implicated in cytokine-regulated proliferation, differentiation and cell
      survival. Interleukin-6 (IL-6), a pleiotropic cytokine, induces a robust and
      sustained activation of STAT3 in M1 acute myeloid leukemia cells, which in turn
      undergo growth arrest, terminal differentiation and apoptosis in response to IL
      6. The roles of STAT3 activation in IL-6-mediated responses in M1 cells are not
      fully understood. We introduced STAT3 antisense cDNA into M1 cells. STAT3
      antisense cDNA blocked the expression and IL-6-induced tyrosine phosphorylation
      and DNA binding of STAT3, and resulted in reduction of both IL-6-induced growth
      arrest at G(0)/G(1) phase and macrophage differentiation in the M1 transformants.
      This observation is in accordance with previous reports and confirms that STAT3
      plays an essential role in IL-6-induced growth arrest and terminal
      differentiation in M1 leukemia cells. On the other hand, STAT3 antisense cDNA
      augmented IL-6-induced apoptosis of M1 cells, which was supported by the cell
      cycle assay, DNA fragmentation assay and detection of the p17 active fragment of
      Caspase 3. As proliferation inhibition and differentiation induction stands for a
      negative signal, while survival maintenance stands for a positive signal, we
      conclude that STAT3 exerts two-way regulation on the biological effects of IL-6
      in M1 leukemia cells.

PMID- 11337019
TI  - Truncated STAT proteins are prevalent at relapse of acute myeloid leukemia.
AB  - Signal transducer and activator of transcription (STAT) proteins are implicated
      in the control of cell survival, proliferation and differentiation in response to
      hematopoietic cytokines. C-terminally truncated STAT isoforms (STATbeta), as
      opposed to the full length form (STATalpha), have a competitive or even
      transdominant negative effect on gene induction mediated by the STAT pathway. We
      have previously demonstrated that while constitutively active STAT proteins were
      detected in ten of 36 (28%) for STAT3 and eight of 36 (22%) for STAT5 in
      pretreatment samples from newly diagnosed acute myeloid leukemia (AML) patients,
      a significantly larger fraction of samples [21 of 27 (78%)] expressed STATbeta
      proteins. To determine whether STATbeta expression was maintained or increased
      after relapse in AML, we compared STAT activity and isoform expression at
      diagnosis and at relapse in 17 patients. In this selected group, constitutively
      active STAT3 was detected in 13 of 17 (76%) AML samples at diagnosis but was
      detected in only four of these patients at relapse. Constitutively active STAT5
      was detected in three of 17 (18%) AML samples at diagnosis; but only two at
      relapse. In contrast, STATbeta protein expression was observed in 12 of the 17
      pretreatment samples (71%) and in 16 of 17 samples at relapse. Only one patient
      did not express STATbeta at relapse. Our results suggest that STATbeta isoform
      expression, rather than level of constitutive activity, may be involved in
      disease progression in AML.

PMID- 11337020
TI  - STAT isoforms: mediators of STAT specificity or leukemogenesis?

PMID- 11337021
TI  - Angiogenesis in B-chronic lymphocytic leukemia.

PMID- 11337022
TI  - Activity of proximal promoter of the human beta(1)-integrin gene was increased in
      Sezary syndrome.
AB  - Changes in beta1-integrin expression have been involved in abnormal cellular
      interactions between malignant lymphocytes from Sezary (Sz) patients and
      keratinocytes. In this paper, we compare the activity of both distal and proximal
      promoters of the beta1-integrin gene in malignant lymphocytes from Sz patients
      with human normal lymphocytes. Activity of both beta1-integrin promoters was also
      analysed in human normal keratinocytes. Northern blot analysis shows that beta1
      integrin mRNA expression is higher in malignant Sz lymphocytes than in normal
      lymphocytes. CAT assays show that the activity of proximal beta1-integrin
      promoter is markedly increased (up to 6-fold) in malignant lymphocytes from Sz
      patients, in comparison to normal lymphocytes. These results suggest that changes
      in activity of the proximal promoter of beta1-integrin subunit could be, in part,
      responsible for the abnormal cellular interactions between malignant lymphocytes
      and keratinocytes observed in Sz syndrome.

PMID- 11337023
TI  - Myelodysplastic and myeloproliferative type of chronic myelomonocytic leukemia-
      distinct subgroups or two stages of the same disease?
AB  - Several authors have tried to solve the problems in the classification of CMML. A
      fully suitable classification does not exist. The goal of our study was to
      determine common and different signs of MD and MP type of CMML and to observe
      frequency of shifts from MD to MP-CMML. Sixty nine CMML patients were divided
      according to FAB proposal into two groups: 31 patients into the MD group (WBC <
      or = 13 x 10(9)/l) and 38 patients into the MP group (WBC < or = 13 x 10(9)/l).
      Presenting features and the course of the disease in both groups were evaluated.
      The median age of patients was not different in both groups (71.5 and 74 years,
      respectively), male/female ratio was 1.1 and 2.4, respectively. The median follow
      up time was 15.5 months (1-58.8) in MP group and 24 months (2-118) in MD group.
      In MP group splenomegaly, hepatomegaly, lymphadenopathy, abnormal karyotype and
      skin involvement were found more often than in MD group. Median LDH value was
      higher in MP group. Probability of survival was higher in the MD group than in MP
      group (median 30 and 11 months, respectively). Leukaemia transformation frequency
      was similar in both groups. In 12 out of 24 (50%) MD group patients WBC increased
      during the course of the disease over 13 x 10(9)/l. Oscillation of WBC values
      below and over 13 x 10(9)/l was observed in three patients. During the follow-up
      time number of patients with splenomegaly and/or immature granulocytes in the PB
      increased. After inclusion of 12 patients who shifted from MD to MP group a new
      CMML group resulted characterised by longer median survival (17 months) due to a
      higher number of patients in an earlier stage of the disease. Failure of
      evolution of myeloproliferative signs and lower frequency of AL in the remaining
      group might be explained by an early stage of CMML, untimely deaths due to
      unrelated causes and/or by patients suffering of RA with monocytosis rather than
      of CMML. In summary, our data suggest, that evolution from MD-CMML to MP-CMML is
      a frequent event and that MD-CMML could be the early stage of CMML in most of
      cases. The WBC at diagnosis as the single criterion for subclassification of CMML
      does not seem to be fully justified. We propose that CMML should not be divided
      in MD and MP types and that monitoring of patients and search for other signs of
      myeloproliferation such as PB immature granulocytes, splenomegaly,
      lymphadenopathy, skin involvement, pleural or peritoneal effusions, spontaneous
      growth of CFU-GM in vitro should be taken in consideration for a better
      classification of CMML, which would have an impact on the therapeutic approach.

PMID- 11337024
TI  - A novel translocation t(2;9)(q14;p12) in AML-M2 with an uncommon phenotype:
      myeloperoxidase-positive and myeloid antigen-negative.
AB  - We report a case of acute myeloid leukemia (AML-M2) expressing myeloperoxidase
      (MPO) but no myeloid antigens. A few cases with this discordant phenotype have
      been reported and an association has been suggested between the lack of CD13 and
      CD33 in MPO positive AML and the presence of t(8;21). Cytogenetic and molecular
      analyses performed in our case showed 48,XY,+Y,+8,t(2;9)(q14;p12). We believe
      that combined approaches can contribute to detect particular AL cases like the
      present one, that confirms the heterogeneity of AML. However, further studies are
      needed to clarify the relationship between phenotypic aberrations and cytogenetic
      abnormalities.

PMID- 11337025
TI  - The psychobiology of anxiolytic drugs. Part 1: Basic neurobiology.
AB  - The authors provide an overview of the current state of knowledge with regards to
      the neurobiological mechanisms involved in normal and pathological anxiety. A
      brief review of the classification and cognitive psychology of anxiety is
      followed by a more in-depth look at the neuroanatomical and neurochemical
      processes and their relevance to our understanding of the modes of action of
      anxiolytic drugs. The serotonergic, noradrenergic, and gamma-aminobutyric
      acidergic systems are reviewed. The numerous physiological and pharmacological
      methods of anxiety provocation and the increasing importance of functional
      neuroimaging are also examined. The review provides an overview of the biology
      and basic pharmacology of anxiolytic drugs, and compliments the more clinically
      oriented companion review.

PMID- 11337026
TI  - The psychobiology of anxiolytic drug.  Part 2: Pharmacological treatments of
      anxiety.
AB  - Benzodiazepines have been the mainstay of pharmacological treatment of anxiety
      over the last 4 decades. The problems associated with their use prompted the
      research for alternative agents that would be useful in anxiety conditions. Old
      classes of antidepressants, such as tricyclic antidepressants and monoamine
      oxidase inhibitors, showed effectiveness in some anxiety syndromes, even in areas
      where benzodiazepines were not very effective. Newer antidepressants, the
      selective serotonin-reuptake inhibitors, also appear very useful in some anxiety
      states, and their favourable side-effect profile has elevated them to first-line
      treatment tools in these conditions. However, the ideal anxiolytic does not
      exist. Research with other new compounds is very active, and some experimental
      drugs show promise for the future.

PMID- 11337027
TI  - The Raf signal transduction cascade as a target for chemotherapeutic intervention
      in growth factor-responsive tumors.
AB  - This review focuses on the Ras-Raf-mitogen-activated protein kinase kinase (MEK)
      extracellular signal-regulated kinase (ERK) signal transduction pathway and the
      consequences of its unregulation in the development of cancer. The roles of some
      of the cell membrane receptors involved in the activation of this pathway, the G
      protein Ras, the Raf, MEK and ERK kinases, the phosphatases that regulate these
      kinases, as well as the downstream transcription factors that become activated,
      are discussed. The roles of the Ras-Raf-MEK-ERK pathway in the regulation of
      apoptosis and cell cycle progression are also analyzed. In addition, potential
      targets for pharmacological intervention in growth factor-responsive cells are
      evaluated.

PMID- 11337028
TI  - Alpha 1-adrenergic receptor regulation: basic science and clinical implications.
AB  - Adrenergic receptors (ARs) are members of the G-protein-coupled receptor family,
      which includes alpha 1ARs, alpha 2ARs, beta 1ARs, beta 2ARs, beta 3ARs,
      adenosine, muscarinic, angiotensin, endothelin receptors, and many others that
      are responsible for a large variety of physiologic effects through G-protein
      coupling. This review focuses on alpha 1ARs and their regulation at both the mRNA
      and protein levels. Currently, three alpha 1AR subtypes have been characterized
      both pharmacologically and at the gene level: alpha 1aAR, alpha 1bAR, and alpha
      1dAR. These are expressed in a species- and tissue-dependent manner. Mutagenesis
      approaches have been extremely valuable in the identification of key residues
      that govern alpha 1AR ligand binding and signaling. These studies reveal that
      alpha 1ARs have evolved an exquisitely sensitive regulation of their activity in
      which any disruption of the native structure has profound effects on subsequent
      function and effector coupling. Significant advances have also been made in the
      elucidation of signaling pathway components, resulting in the identification of
      novel pathways that can lead to pathologic conditions. Specific topics include
      mitogen-activated protein kinase, phosphatidylinositol 3-kinase, and G-protein
      coupled receptor cross-talk pathways. Within this context, recent studies
      identifying underlying transcriptional mechanisms involved in the regulation of
      the alpha 1AR subtypes are also discussed. Finally, given the potentially
      important role of alpha 1ARs in the vasculature, as well as in the pathology of
      many diseases, such as myocardial hypertrophy and benign prostatic hyperplasia,
      the clinical relevance of alpha 1AR distribution, pharmacology, and therapeutic
      intervention is reviewed.

PMID- 11337029
TI  - Pharmacological modulation, preclinical studies, and new clinical features of
      myocardial ischemic preconditioning.
AB  - The term "ischemic preconditioning (PC)" was first applied to canine myocardium
      subjected to brief episodes of ischemia and reperfusion that tolerated a more
      prolonged episode of ischemia better than myocardium not previously exposed to
      ischemia. Protective effect of myocardial ischemic PC was demonstrated in several
      animal species, resulting in the strongest endogenous form of protection against
      myocardial injury, jeopardized myocardium, infarct size, and arrhythmias other
      than early reperfusion. New onset angina before acute myocardial infarction,
      episodes of myocardial ischemia during coronary angioplasty or bypass surgery,
      and the "warm-up" phenomenon may represent clinical counterparts of the PC
      phenomenon in humans. Here, we have attempted to summarize pharmacological
      modulation, preclinical studies, and new clinical features of ischemic PC. To
      date, the pathophysiological basis of the "chemical PC" is still not well
      established, and "putting PC in a bottle" for clinical applications still remains
      a new pharmacological venture.

PMID- 11337030
TI  - Death the Fas way: regulation and pathophysiology of CD95 and its ligand.
AB  - Apoptotic cell death mediated by the members of the tumor necrosis factor
      receptor family is an essential process involved in the regulation of cellular
      homeostasis during development, differentiation, and pathophysiological
      conditions. Among the cell death receptors comprising the tumor necrosis factor
      receptor superfamily, CD95/APO-1 (Fas) is the best characterized. The specific
      interaction of Fas with its cognate ligand, Fas ligand (FasL), elicits the
      activation of a death-inducing caspase (cysteine aspartic acid proteases)
      cascade, occurring in a transcription-independent manner. Caspase activation
      executes the apoptosis process by cleaving various intracellular substrates,
      leading to genomic DNA fragmentation, cell membrane blebbing, and the exposure of
      phagocytosis signaling molecules on the cell surface. Recent studies have shown
      that the Fas/FasL pathway plays an important role in regulating the life and
      death of the immune system through activation-induced cell death. In addition,
      these molecules have been implicated in aging, human immunodeficiency virus
      infection, drug abuse, stress, and cancer development. In this review, we will
      focus on the mechanisms that regulate Fas and FasL expression, and how their
      deregulation leads to diseases.

PMID- 11337031
TI  - Purine nucleoside phosphorylases: properties, functions, and clinical aspects.
AB  - The ubiquitous purine nucleoside phosphorylases (PNPs) play a key role in the
      purine salvage pathway, and PNP deficiency in humans leads to an impairment of T
      cell function, usually with no apparent effects on B-cell function. This review
      updates the properties of the enzymes from eukaryotes and a wide range of
      prokaryotes, including a tentative classification of the enzymes from various
      sources, based on three-dimensional structures in the solid state, subunit
      composition, amino acid sequences, and substrate specificities. Attention is
      drawn to the compelling need of quantitative experimental data on subunit
      composition in solution, binding constants, and stoichiometry of binding; order
      of ligand binding and release; and its possible relevance to the complex kinetics
      exhibited with some substrates. Mutations responsible for PNP deficiency are
      described, as well as clinical methods, including gene therapy, for corrections
      of this usually fatal disease. Substrate discrimination between enzymes from
      different sources is also being profited from for development of tumour-directed
      gene therapy. Detailed accounts are presented of design of potent inhibitors,
      largely nucleosides and acyclonucleosides, their phosphates and phosphonates,
      particularly of the human erythrocyte enzyme, some with Ki values in nanomolar
      and picomolar range, intended for induction of the immunodeficient state for
      clinical applications, such as prevention of host-versus-graft response in organ
      transplantations. Methods of assay of PNP activity are reviewed. Also described
      are applications of PNP from various sources as tools for the enzymatic synthesis
      of otherwise inaccessible therapeutic nucleoside analogues, as coupling enzymes
      for assays of orthophosphate in biological systems in the micromolar and
      submicromolar ranges, and for coupled assays of other enzyme systems.

PMID- 11337032
TI  - Distribution and roles of metabotropic glutamate receptors in the basal ganglia
      motor circuit: implications for treatment of Parkinson's disease and related
      disorders.
AB  - The basal ganglia (BG) are a set of interconnected subcortical structures that
      play a critical role in motor control. The BG are thought to control movements by
      a delicate balance of transmission through two BG circuits that connect the input
      and output nuclei: the direct and the indirect pathways. The BG are also involved
      in a number of movement disorders. Most notably, the primary pathophysiological
      change that gives rise to the motor symptoms of Parkinson's Disease (PD) is the
      loss of dopaminergic neurons of the substantia nigra pars compacta (SNc) that are
      involved in modulating function of the striatum and other BG structures. This
      ultimately results in an increase in activity of the indirect pathway relative to
      the direct pathway and the hallmark PD symptoms of rigidity, bradykinesia, and
      akinesia. A great deal of effort has been dedicated to finding treatments for
      this disease. The current pharmacotherapies are aimed at replacing the missing
      dopamine, while the current surgical treatments are aimed at reducing
      transmission through the indirect pathway. Dopamine replacement therapy has
      proven to be helpful, but is associated with severe side effects that limit
      treatment and a loss of efficacy with progression of the disease. Recently
      developed surgical therapies have been highly effective, but are highly invasive,
      expensive, and assessable to a small minority of patients. For these reasons, new
      effort has been dedicated to finding pharmacological treatment options that will
      be effective in reducing transmission through the indirect pathway. Members of
      the metabotropic glutamate receptor (mGluR) family have emerged as interesting
      and promising targets for such a treatment. This review will explore the most
      recent advances in the understanding of mGluR localization and function in the BG
      motor circuit and the implications of those findings for the potential
      therapeutic role of mGluR-targeted compounds for PD.

PMID- 11337033
TI  - Endomorphin-1 and endomorphin-2: pharmacology of the selective endogenous mu
      opioid receptor agonists.
AB  - The recently discovered endogenous opioid peptides, endomorphins-1 and -2, appear
      to have properties consistent with neurotransmitter/neuromodulator actions in
      mammals. This review surveys the information gained so far from studies of
      different aspects of the endomorphins. Thus, the endomorphins have been found
      unequally in the brain; they are stored in neurons and axon terminals, with a
      heterogeneous distribution; they are released from synaptosomes by
      depolarization; they are enzymatically converted by endopeptidases; and they
      interact specifically and with high affinity with mu-opioid receptors. The most
      outstanding effect of the endomorphins is their antinociceptive action. This
      depends on both central and peripheral neurons. Additionally, the endomorphins
      cause vasodilatation by stimulating nitric oxide release from the endothelium.
      Their roles in different central and peripheral functions, however, have not been
      fully clarified yet. From a therapeutic perspective, therefore, they may be
      conceived at present as potent antinociceptive and vasodilator agents.

PMID- 11337034
TI  - A novel retroviral vector that allows the magnetic selection of infected cells.
AB  - Retroviral vectors are used widely in research and are also being designed for
      use in gene therapy trials. In practice, these vectors usually contain a marker
      gene, which is often a drug selection gene. In this report, a novel retroviral
      vector has been constructed which contains a gene that allows selection for
      infected cells by a magnet. This gene is a single-chain antibody (sFv) to a
      specific hapten molecule 4-ethoxymethylene-2-phenyl-2-oxazolin-5-one (phOx). sFv
      specific for phOx is displayed on the surface of infected cells. This feature
      allows binding to phOx-BSA coated magnetic beads which are used to isolate the
      infected cells.

PMID- 11337035
TI  - PCR-based plasmid vector construction for generation of recombinant viruses.
AB  - A totally polymerase chain reaction (PCR)-based protocol for construction of
      plasmids for production of recombinant macropodid herpesvirus 1 (MaHV-1) is
      described. This protocol greatly simplifies traditional methods that use
      restriction enzyme-based cloning or a combination of restriction enzyme cloning
      and the PCR. PCR is used to amplify the vector backbone containing an origin of
      replication and selectable marker, and the inserts to be cloned (5' and 3' viral
      homologous recombination regions and the reporter gene green fluorescent protein
      (GFP)). The inserts are cloned in a sequential manner with the intermediate
      vectors then amplified to produce the next vector. At its most basic, this
      involves, after the initial PCR amplification of vector and inserts, two
      additional PCR amplifications and three ligation events. This protocol is however
      totally generic, and can be used not only for construction of plasmids for
      production of recombinant viruses, but also for any general cloning applications.

PMID- 11337036
TI  - Antibody masking renders HIV-1 resistant to cationic membrane filtration through
      alteration of its electrostatic characteristics.
AB  - Previously, it was demonstrated that any human immunodeficiency virus type 1 (HIV
      1) strain proliferating in peripheral blood mononuclear cells (PBMCs) in vitro,
      and resuspended in seronegative plasma, could be captured efficiently (mean >
      95%) by a porous polypropylene (PP) membrane modified cationically. We
      investigated if this cationic membrane could capture HIV-1 obtained from
      seropositive plasma, and confirmed whether this membrane was effective for the
      preparation of safe plasma products against HIV-1 transmission. Thirty-six
      seropositive plasma samples derived from HIV-1 positive cohorts in New York and
      Lusaka (Republic of Zambia), including 18 cases of acquired immunodeficiency
      syndrome (AIDS) related complex, AIDS and five terminal cases of AIDS, were
      filtered through the cationic membrane to determine the reduction of RNA
      concentration, the gag p24 concentration, and infectious titer. Only a small
      reduction in RNA concentration (mean < 20%) and almost no decrease in gag
      concentration (mean < 2%) were obtained, despite the fact that the infectivity
      was eliminated entirely by the filtration. Due to the possibility that anti-HIV-1
      antibodies in patients' plasma combine with HIV-1, laboratory-adapted HIV-1(HTLV
      IIIB) was mixed with seropositive plasma to test the effect of antibodies on HIV
      1 adsorption, and also to investigate the interfacial electrokinetic potential
      (zeta-potential) of both intact and plasma-treated HIV-1. The zeta-potential of
      HIV-1(HTLV-IIIB) in the presence of seropositive plasma was neutral as opposed to
      negative when stored in seronegative plasma or culture medium. Also the rate of
      HIV-1 capture by the membrane, as determined by the reduction in RNA
      concentration, sank from 95% to 20%, the same capture percentage observed when
      filtering plasma of patients. These findings suggested that in patients' plasma,
      the antibody-masked HIV-1 comprise most of the viral population, and was not
      trapped on the cationic membrane because of its electrostatic character.
      Conversely, the cationic membrane was thought to adsorb antibody-free HIV-1
      exclusively. It was suggested that each viral swarm had its own zeta-potential,
      and this difference in electrostatic character determined the extent of the viral
      adsorption by the cationic membrane.

PMID- 11337037
TI  - Improved method for the recovery of hepatitis A virus from oysters.
AB  - Hepatitis A is one of the major infectious diseases epidemiologically associated
      with worldwide shellfish consumption. Molecular detection using polymerase chain
      reaction (PCR) to detect hepatitis A virus (HAV) in contaminated shellfish can be
      hindered by low virus recoveries during the concentration process and by natural
      PCR inhibitors in shellfish. This study evaluated and modified two major steps of
      a processing procedure for virus concentration from oysters: acid adsorption
      elution and solvent extraction. With the addition of second and third elutions,
      the acid adsorption-elution step doubled the recovery to 46% of HAV seeded
      initially. Extraction with chloroform or chloroform-butanol resulted in lower HAV
      detection limits by reverse transcription-PCR (RT-PCR)-oligoprobing than
      extraction with the fluorocarbon, Freon. These results led to the following
      modified procedure: HAV was acid adsorbed at pH 4.8, eluted first with 0.05 M
      glycine, second with 0.5 M threonine, PEG-precipitated twice, chloroform
      extracted twice, RNA-extracted, and RT-PCR (single round) amplified. Using the
      modified procedure, HAV was detected by RT-PCR in all trials with a seeding
      density of > or = 1 plaque forming unit (PFU)/g of oyster, and in which the
      equivalent detection limit was 0.33 PFU of HAV seeded per RT-PCR reaction
      (corresponding to 111 PCR units). The method developed is capable of detecting
      low levels of HAV in oysters environmentally contaminated.

PMID- 11337038
TI  - Random mutagenesis in a plant viral genome using a DNA repair-deficient mutator
      Escherichia coli strain.
AB  - Random mutagenesis in a plant viral genome is valuable for generating attenuated
      strains or for analyzing viral gene function at the molecular level. A DNA repair
      deficient mutator Escherichia coli strain was used for random mutagenesis of a
      plant viral genome. A full-length infectious cDNA clone of Citrus tatter leaf
      virus (genus Capillovirus) L strain (CTLV-L) genomic RNA under the T7 promoter
      sequence (pITCL) was introduced into the mutator E. coli strain XL1-Red and
      mutagenized overnight. To fix mutations, the mixture of plasmid DNA isolated from
      colonies of the mutator bacteria was introduced into another E. coli strain,
      JM109, which has normal DNA repair function. Infectious viral genomic RNA was
      transcribed in vitro from each mutagenized pITCL clone and inoculated on host
      plants. Phenotypic mutants were selected for altered pathogenicity in the
      inoculated plants. Nucleotide sequence analysis of each mutant revealed that
      mutations were introduced randomly into the CTLV-L genome regardless of the
      function of the viral gene. The nucleotide substitutions were biased towards
      single point mutations, which consisted of more transitions than transversions or
      single-base frameshifts. These mutations were preserved stably in plants subject
      to sequential mechanical inoculation. The strategy presented below is a simple
      and very efficient way to generate virus mutants for analyzing the functions of
      viral genes.

PMID- 11337039
TI  - HIV-1 subtyping using phylogenetic analysis of pol gene sequences.
AB  - HIV-1 pol gene sequencing is now used routinely in France to identify mutations
      associated with resistance to reverse transcriptase (RT) or protease (PR)
      inhibitors. These sequences may also provide other information, such as the HIV-1
      subtype. HIV-1 subtyping was compared using the RT and PR gene sequences to
      heteroduplex mobility assay (HMA) of the envelope gene. The RT and PR genes of 51
      samples that had been subtyped earlier by HMA were sequenced. Sequences were
      aligned and subtypes were determined by phylogenetic analysis with reference HIV
      sequences. HMA gave the following subtypes: A (20), B (19), C (1), D (3), F (1),
      G (3) and CRF01-AE (4). Phylogenetic analysis of the RT gene gave: A (5), B (19),
      C (2), D (3), F (1), G (6), J (2), CRF01_AE (4), CFR02_AG (7) and undetermined
      (2). PR gene analysis did not infer subtypes with sufficient confidence. HMA and
      RT subtyping was not in agreement in nine cases. RT subtyping can identify
      CFR02_AG and CRF01_AE variants from A subtype RT. It was shown that phylogenetic
      analysis of the RT gene could provide a useful method for HIV-1 subtyping. The
      length of the amplicon and the relative performance of each primer pair used in
      this study favoured RT sequences as a subtyping tool. One potential advantage
      over env subtyping HMA is the ability to identify some circulating recombinant
      forms (CRFs).

PMID- 11337040
TI  - Inducible model to study negative strand RNA synthesis and assembly of hepatitis
      C virus from a full-length cDNA clone.
AB  - An inducible in vitro cell culture system was developed to assay HCV replication
      by direct biochemical means. A transcription plasmid containing a T7 promoter at
      the 5' end, full-length cDNA of the HCV genome, a ribozyme sequence from the
      antigenomic strand of hepatitis delta virus and a T7 terminator was prepared. To
      facilitate high-level transcription of HCV RNA, HepG2 cells were infected with
      replication deficient adenovirus containing the T7 RNA polymerase gene and later
      transfected with the transcription plasmid containing the full-length HCV genome.
      This transfection-based cell culture system expressed high levels of HCV
      structural (core, El and E2) and non-structural proteins (NS3 and NS5B)
      detectable by Western blot and immunofluorescence assays. Production of HCV RNA
      transcripts and presence of replicative negative strand of HCV was confirmed by
      ribonuclease protection assay indicating replication of HCV in the transfected
      HepG2 cell. The transfected HepG2 cells assembled 50-60 nm virus-like particles,
      which could be aggregated by anti-E2 antibodies. This model can be utilized for
      studying mechanisms of HCV replication, assembly of HCV particles and to test
      potential anti-HCV compounds.

PMID- 11337041
TI  - Immunochemiluminescent focus assays for the quantitation of hepatitis A virus and
      rotavirus in cell cultures.
AB  - Two new immunological methods, the luminescent immunofocus assay (LIFA) and the
      luminescent immunofocus inhibition assay (LIF-IA), are described for the
      quantitation of cytopathic and non-cytopathic viruses propagated on cell culture
      monolayers. These methods use enhanced chemiluminescent detection to identify
      foci (luminescent immunofoci, LIF) of virus-infected cells. Viruses are
      propagated in susceptible cells under an agarose overlay, inactivated with
      ultraviolet irradiation, lifted onto nitrocellulose membranes, and probed with
      virus-specific monoclonal or polyclonal antibody followed by a second antibody
      conjugated to horseradish peroxidase. Membranes are then treated with a luminol
      based detection reagent and exposed to light sensitive film for up to 10 min. The
      film is developed and foci appear as dark, discrete spots which are proportional
      to the dose of each virus. The LIFA detected both cytopathic and non-cytopathic
      hepatitis A viruses (HAV) and simian rotavirus. For the cytopathic HAV, the LIFA
      and plaque counts were comparable. The LIF-IA was developed for HAV using virus
      specific antiserum which effectively attenuated LIF formation. The LIFA and LIF
      IA may be completed 5 days faster than conventional radioimmunofocus assays for
      HAV and rotavirus and do not require the use of radiolabeled antibodies, offering
      safety advantages and making these techniques more adaptable for general use.
      Luminescent immunofocus assays should be useful for the detection and
      quantitation of virtually any cytopathic or non-cytopathic virus that can be
      propagated in monolayer cultures when virus-specific antiserum is available.

PMID- 11337042
TI  - Genomic characterization of pestiviruses isolated from lambs and kids in southern
      Italy.
AB  - A nested polymerase chain reaction was used to identify 13 pestivirus strains
      isolated from small ruminants in several mixed (sheep and goats) flocks of
      Southern Italy, and for classification as bovine viral diarrhoea virus (BVDV)
      type 1, BVDV type 2, and Border disease virus (BDV) genotypes. Of the nine ovine
      isolates, two were characterized as BVDV type 1, and seven as BVDV type 2. The
      four pestiviruses isolated from kids belong to BVDV type 1. None of the
      pestivirus strains tested could be classified as 'true' BDV (genotype 3).
      Although BVDV type 2 has been described in Europe rarely, the characterization of
      BD/90-1M strain as BVDV type 2, isolated in Italy in 1990, demonstrates that this
      genotype has been circulating in Italy since the 1990s.

PMID- 11337043
TI  - A highly prevalent polymorphism at codon 72 of HIV-1 reverse transcriptase in
      Argentina prevents hybridization reaction at codon 74 in the LiPA genotyping
      test.
AB  - The aim of this study was to compare the performance of two commercial drug
      resistance HIV-1genotyping kits: LiPA (Innogenetics, Belgium) and TruGene
      (Visible Genetics, Canada). Samples from 103 HIV-1 infected individuals from
      Argentina were studied. The average correlation between the two methods was
      92.81%. More codons could be analysed by TruGene than by LiPA (610/618 and
      541/618 codons, respectively). The sequences of the samples and the LiPA probes
      were aligned showing that a silent mutation at codon 72 (AGA-->AGG) of the HIV-1
      reverse transcriptase, which was not recognised by the LiPA probes, was present
      in 35/36 non-reactive samples for position 74. The overall prevalence of this
      polymorphism in the population studied was 39.81%. When sequences from different
      parts of the world were analysed 189/3395 (5.63%) carried the mutation at codon
      72, while 23/133 (17.29%) of the sequences from Latin America (excluding
      Argentina) had this mutation. In both cases, the prevalence of this polymorphism
      in the Argentinean population was significantly higher. This highlights the
      importance of carrying out studies on the performance of genotyping kits outside
      the United States and Europe, especially in areas where non-B HIV-1 subtypes are
      prevalent.

PMID- 11337044
TI  - Detection of horses infected naturally with equine infectious anemia virus by
      nested polymerase chain reaction.
AB  - A nested polymerase chain reaction (PCR) amplifying a region of the gag gene of
      equine infectious anemia virus (EIAV) was developed for the rapid and direct
      detection of proviral DNA from the peripheral blood of naturally infected horses
      and was compared with the Coggins test. DNA prepared from white blood cells of
      122 field horses from 15 stables with reported cases of EIAV and one seronegative
      stable were analysed. Amplifications of expected size fragments were obtained by
      nested PCR for 88 horses using two different sets of primers targeting the gag
      region. The specificity of the amplified products was confirmed by hybridization
      using a digoxigenin-labeled probe. Gag-nested PCR-restriction fragment length
      polymorphism analysis distinguished two different subtypes of gag gene, A and B.
      Subtype A was found to be the most prevalent among the infected horses that were
      tested. The PCR-gag amplified sequence of subtype A shared 84.6% nucleotide and
      93% deduced amino acid sequence identities with the prototype Wyoming strain
      whereas subtype B sequence was almost 100% identical to the prototype. Sequence
      analysis of gag subtype A suggests the presence of a novel EIAV variant among
      infected horses in Canada. The nested PCR assay developed in the present study
      detected more EIAV positive animals and was found as specific as the agar gel
      immunodiffusion (Coggins) assay and offers great potential a diagnostic test for
      the detection of EIAV infections in field horses.

PMID- 11337045
TI  - Development of a strand-specific RT-PCR based assay to detect the replicative
      form of hepatitis C virus RNA.
AB  - The recent development of tagged RT-PCR and rTth RT-PCR has greatly improved
      strand-specific detection of hepatitis C virus (HCV) RNA but these assays are
      still prone to some false detection of the incorrect strand of RNA. In this study
      we aimed to address additional factors which contribute towards false detection
      of HCV RNA. Firstly the benefits of both tagged primers and the thermostable
      reverse transcriptase rTth during cDNA synthesis were combined and it was found
      that strand specificity was greatly improved without compromising sensitivity.
      The reliability of the assay was then optimised by addressing the following
      issues: control synthetic transcripts should be free of contaminating plasmid
      DNA, residual RT activity should be minimised in the presence of PCR primers and
      cDNA should be free of unincorporated tagged RT primer prior to PCR
      amplification. The alterations made to the assay eliminated completely false
      detection of the incorrect strand of RNA in the control assay whilst the correct
      strand was consistently detected at a cDNA dilution of 10(-3)-10(-4). Negative
      strand was not detected in RNA isolated from serum but was detected, at a ten
      fold lower level than positive strand, in RNA isolated from liver tissue.

PMID- 11337046
TI  - Detection of arboviral RNA directly from mosquito homogenates by reverse
      transcription-polymerase chain reaction.
AB  - Many arthropod-borne viruses (arboviruses) are important human pathogens
      medically. The development of an effective technique to detect the viruses by
      using nucleic acid amplification, such as polymerase chain reaction (PCR),
      improves not only clinical diagnosis but also virologic surveillance of mosquito
      vectors in the field. In this study, the development of an improved and
      simplified assay is described for detection of mosquitoes infected with eastern
      equine encephalitis (EEE) virus, Cache Valley (CV), and California (CAL)
      serogroup viruses from field-collected mosquito pools. As little as 5 microl of
      homogenate from mosquito pools was used in the reverse transcription (RT)
      reaction followed by the use of three sets of specific primers for the PCR.
      Positive pools were determined by finding PCR bands of the expected size for each
      arbovirus. The confirmation and identification of Bunyaviruses was done by
      sequencing the PCR product. In 1999, West Nile virus (WNV) was identified as the
      etiologic agent of an outbreak of human encephalitis in New York City. It is
      shown that this protocol is also able to detect West Nile viral RNA in a pool of
      100 mosquitoes containing one infected mosquito.

PMID- 11337047
TI  - Comparison of different methods of total RNA extraction for viral detection in
      sputum.
AB  - Examination of sputum specimens can be used for monitoring airway inflammation by
      means of immunological and molecular techniques. RNA extraction is essential for
      measurement of cytokine gene expression and for detection of many viral pathogens
      in sputum. In this study, three RNA extraction methods used commonly (acid
      guanidinium thiocyanate-phenol-chloroform extraction, Trizol and RNeasy Mini kit)
      were compared on the sputum of 14 patients who had chronic obstructive pulmonary
      disease. The effect of dithiothreitol pre-treatment on sputum RNA extraction was
      also investigated. The yield and purity of total RNA were determined by
      spectrophotometry. Reverse transcription-polymerase chain reaction (RT-PCR)
      results of the house keeping gene (glyceraldehyde-3-phosphate dehydrogenase) and
      RNA sequences specific to common respiratory viruses were compared. The results
      showed that (1) total RNA extracted with Trizol had highest yield and purity
      among the three RNA extraction methods; (2) there was no significant difference
      among the three RNA extraction methods on the house keeping gene and viral
      detection by RT-PCR; (3) dithiothreitol pre-treatment did not improve either the
      purity of total RNA, or RT-PCR signal. Moreover, dithiothreitol treatment reduced
      significantly the yield of total RNA. The results of the study indicate that the
      Trizol method appears to be superior for total RNA extraction from sputum, and
      dithiothreitol pre-treatment does not increase the efficiency of RNA extraction
      and RNA detection in sputum specimens.

PMID- 11337048
TI  - Establishment of AIDS-related primary-effusion lymphoma (PEL) cell lines that
      proliferate continuously without serum.
AB  - The gammaherpesvirus dually-infected (HHV8/EBV) PEL cell line, BC-1, was weaned
      gradually from fetal bovine serum (FBS) during successive feedings with RPMI 1640
      medium containing human transferrin and selenium dioxide as the only additives. A
      serum-free cell line (sfBC-1) emerged that was 100% major histocompatibility
      complex (MHC) class II negative, compared with 10% MHC class II-negative cells
      before serum removal. In contrast, MHC class I expression by sfBC-1 cells
      slightly exceeded that of BC-1 cells. BC-1 and sfBC-1 cells were
      indistinguishable in six polymorphic genetic loci, confirming their relatedness
      and sfBC-1 cells contained HHV8 and EBV. These findings were not attributable to
      dual infection because the PEL cell line, BCBL-1, which is infected with HHV8 but
      not EBV, also contained MHC class II positive (45%) and class II negative (55%)
      cells. Moreover, a serum-free BCBL-1 (sfBCBL-1) cell line was established and the
      sfBCBL-1 cells were MHC class I up modulated and 100% MHC class II negative. The
      serum-free cell lines established in this study may be useful for exploring PEL
      cell autocrine-growth pathways and for assessing MHC class II-negative PEL cells
      for tumorigenesis in animal model systems.

PMID- 11337049
TI  - Determination of bovine adenovirus-3 titer based on immunohistochemical detection
      of DNA binding protein in infected cells.
AB  - DNA sequence coding for a portion of DNA binding protein (amino acids 3-58) of
      bovine adenovirus type-3 (BAV-3) was cloned and expressed in Escherichia coli as
      a fusion protein with Schistosoma japonicum glutathione S-transferase. The fusion
      protein was affinity purified and used to immunize rabbits. Immunoprecipitation
      and Western blot analysis showed that the antiserum could specifically recognize
      a protein of 48 kDa in BAV-3-infected cells, which was produced both in early and
      late phases of BAV-3 life cycle. Based on the ability of antiserum to recognize
      DNA binding protein, a novel assay for BAV-3 quantitation was established. The
      assay is less time consuming and can be performed on a wide variety of bovine
      cells. In addition, virus titers determined by this assay are comparable to the
      standard plaque assay.

PMID- 11337050
TI  - A quantitative assay for measuring human foamy virus using an established
      indicator cell line.
AB  - In order to improve the accuracy for detecting human foamy virus (HFV), an
      indicator cell line was established by co-transfecting baby hamster kidney-21
      cells with two plasmids: one containing a G418 antibiotic resistance marker and
      the other including the luc gene which was placed downstream of the inducible HFV
      long terminal repeat promoter (from -533 to +20). Among 11 independent subclones,
      IdB14 was found to be stable with a low basal level of luciferase activity.
      Although the changes in luciferase activity in infected clones showed time
      dependency and peaked at day 8, it is possible to differentiate infected and
      uninfected cells on day 2. The sensitivity of the foamy virus activated
      luciferase (FAL) assay was 400 times higher than the end-point syncytium
      formation by TCID(50). The HFV LTR promoter in the IdB14 cell line was specific
      for this virus. Moreover, a linear relationship was found between the MOI and the
      activated intensity of luciferase expression. These findings suggest that the FAL
      assay using the IdB14 indicator cell line is a simple and useful technique for
      rapid diagnosis and quantitation of active HFV infection.

PMID- 11337051
TI  - HHV-8 ELISA based on a one-step affinity capture of biotinylated K8.1 antigen.
AB  - The immunogenic envelope antigen gp35-37 of human herpesvirus-8 (HHV-8) is
      encoded by orfK8.1. An ELISA is described using streptavidin capture of
      bacterially expressed and biotinylated recombinant K8.1 antigen. The antigen
      capture strategy provides a simple and reliable method, which does not require
      high yield production and purification of the recombinant antigen before the
      serological assay. The specificity and sensitivity of the K8.1 ELISA were
      validated by gp35-37 envelope antigen Western blot and anti-lytic membrane
      immunofluorescence assay using lytically induced HHV-8 infected BCBL-1 cells.
      Under the established ELISA conditions, eight of the 10 Kaposi's sarcoma patients
      and five of the 180 healthy blood donors had IgG antibodies to K8.1 envelope
      antigen.

PMID- 11337053
TI  - Specific detection of RT activity in culture supernantants of retrovirus
      producing cells, using synthetic DNA as competitor in polymerase enhanced reverse
      transcriptase assay.
AB  - The polymerase enhanced reverse transcriptase (PERT) assay is a highly sensitive
      assay for the detection of reverse transcriptase (RT) activity in culture
      supernatants of retrovirus-producing cells. However, some cellular DNA-dependent
      DNA polymerases exhibit RT-like activities in this assay. A synthetic DNA
      competitor which suppresses the RT-like activities of cellular DNA-dependent DNA
      polymerases was used in a modified PERT assay technique for specific detection of
      RT activity in culture supernatants of retrovirus-producing cells. We determined
      the optimum condition of the assay and evaluated its specificity. This improved
      PERT assay is easy to perform and is able to detect minute amounts of purified
      RT, as well as RT in crude cell lysates and concentrated culture supernatants.

PMID- 11337052
TI  - Decreased pulmonary clearance of S. pneumoniae following influenza A infection in
      mice.
AB  - In children, the incidence of complicated pneumonias (including empyemas and lung
      abscesses) associated with Streptococcus pneumoniae infection has increased in
      recent years. In many cases, these complicated pneumonias followed flu-like
      illnesses. To determine mechanisms behind this association, a murine model of
      sequential pulmonary infection has been developed. BALB/cJ mice infected with
      influenza A had mild pulmonary inflammation that resolved within 5-7 days. Seven
      days following their initial 'treatment' (mock infection or influenza exposure),
      mice were challenged with 10(6) cfu of S. pneumoniae, and their lungs were
      harvested at intervals for analysis. Lungs of influenza-exposed mice demonstrated
      greater colony counts 24 and 48 h following S. pneumoniae exposure compared to
      control mice. In addition, neutrophil numbers were significantly increased in the
      influenza/S. pneumoniae sequentially-infected animals compared to S. pneumoniae
      infection alone (1.4+/-0.6 x 10(6) vs. 0.06+/-0.07 x 10(6) cells, P < 0.05, 24
      h). Influenza-exposed animals had greater levels of IL-1beta and TNF-alpha in
      lung homogenates following S. pneumoniae inoculation. These data demonstrate that
      mice exposed to influenza have enhanced inflammatory responses and increased
      bacterial burden following S. pneumoniae exposure than do control mice. This
      model will be useful in defining mechanisms behind the enhanced susceptibility to
      S. pneumoniae that occurs after influenza exposure.

PMID- 11337054
TI  - Hybrid nanogels for sustainable positive thermosensitive drug release.
AB  - A hybrid nanogel has been developed based on interpenetrating networks of
      thermosensitive poly(N-isopropylacrylamide) gels and tailored nanoporous silica.
      A sustainable positive thermo-responsive drug release profile is obtained. When
      the temperature rises, the polymer gel shrinks, squeezing the drug into the
      porous channels, and at the same time, opening the pores to the outside media.
      The drug slowly diffuses out of the porous channels. The overall release rate can
      be adjusted by changing the composition of the nanogel.

PMID- 11337055
TI  - Brush-like branched biodegradable polyesters, part III. Protein release from
      microspheres of poly(vinyl alcohol)-graft-poly(D,L-lactic-co-glycolic acid).
AB  - Brush-like branched polyesters, obtained by grafting poly(lactic-co-glycolic
      acid), PLGA, onto water-soluble poly(vinyl alcohol) (PVAL) backbones, were
      investigated regarding their utility for the microencapsulation of proteins.
      Poly(vinyl alcohol)-graft-poly(lactic-co-glycolic acid), PVAL-g-PLGA, offers
      additional degrees of freedom to manipulate properties such as e.g. molecular
      weight, glass transition temperature and hydrophilicity. PLGA chain length was
      varied at a constant molecular weight (M(w)) of the PVAL backbone and secondly
      M(w) of the PVAL backbone was varied keeping the PLGA chain lengths constant. The
      most striking feature of these polymers is their high M(w). Microencapsulation of
      hydrophilic macromolecules, such as bovine serum albumin, ovalbumin, cytochrome c
      and FITC-dextran using a w/o/w double emulsion technique was investigated.
      Surface morphology, particle size, encapsulation efficiencies and protein release
      profiles were characterized as well. Microencapsulation of model compounds was
      feasible at temperatures of 0-4 degrees C with yields typically in the range of
      60-85% and encapsulation efficiencies of 70-90%. Both, encapsulation efficiency
      and initial protein release (drug burst) were strongly affected by the glass
      transition temperature, T(g), of the polymer in contact with water, whereas the
      in vitro protein release profile depended on the PVAL-g-PLGA structure and
      composition. In contrast to PLGA, protein release patterns were mostly continuous
      with lower initial drug bursts. Shorter PLGA chains increased drug release in the
      erosion phase, whereas initial pore diffusion was affected by the M(w) of PVAL
      backbone. Release profiles from 2 to 12 weeks could be attained by modification
      of composition and molecular weight of PVAL-g-PLGA and merit further
      investigations under in vivo conditions. The in vitro cytotoxicity of PVAL-g-PLGA
      is comparable to PLGA and therefore, this new class of biodegradable polyesters
      has considerable potential for parenteral drug delivery systems.

PMID- 11337056
TI  - Model prodrugs for the intestinal oligopeptide transporter: model drug release in
      aqueous solution and in various biological media.
AB  - The human intestinal di/tri-peptide carrier, hPepT1, has been suggested as a
      target for increasing intestinal transport of low permeability compounds by
      creating prodrugs designed for the transporter. Model ester prodrugs using the
      stabilized dipeptides D-Glu-Ala and D-Asp-Ala as pro-moieties for benzyl alcohol
      have been shown to have affinity for hPepT1. Furthermore, in aqueous solution at
      pH 5.5 to 10, the release of the model drug seems to be controlled by a specific
      base-catalyzed hydrolysis, indicating that the compounds may remain relatively
      stable in the upper small intestinal lumen with a pH of approximately 6.0, but
      still release the model drug at the intercellular and blood pH of approximately
      7.4. Even though benzyl alcohol is not a low molecular weight drug molecule,
      these results indicate that the dipeptide prodrug principle is a promising drug
      delivery concept. However, the physico-chemical properties such as
      electronegativity, solubility, and log P of the drug molecule may also have an
      influence on the potential of these kinds of prodrugs. The purpose of the present
      study is to investigate whether the model drug electronegativity, estimated as
      Taft substitution parameter (sigma*) may influence the acid, water or base
      catalyzed model drug release rates, when released from series of D-Glu-Ala and D
      Asp-Ala pro-moieties. Release rates were investigated in both aqueous solutions
      with varying pH, ionic strength, and buffer concentrations as well as in in vitro
      biological media. The release rates of all the investigated model drug molecules
      followed first-order kinetics and were dependent on buffer concentration, pH,
      ionic strength, and model drug electronegativity. The electronegativity of the
      model drug influenced acid, water and base catalyzed release from D-Asp-Ala and D
      Glu-Ala pro-moieties. The model drug was generally released faster from D-Asp-Ala
      than from the D-Glu-Ala pro-moieties. In biological media the release rate was
      also dependent on the electronegativity of the model drug. These results
      demonstrate that the model drug electronegativity, estimated as Taft (sigma*)
      values, has a significant influence on the release rate of the model drug.

PMID- 11337057
TI  - Transbuccal peptide delivery: stability and in vitro permeation studies on
      endomorphin-1.
AB  - The purpose of this study was to investigate the feasibility of buccal delivery
      of a model peptide, endomorphin-1 (ENI), using stability and in vitro permeation
      studies. ENI is a recently isolated mu-opiate receptor agonist with high
      selectivity and specificity for this receptor subtype. Stability studies were
      conducted in various buffers and the drug was shown to be stable in both acidic
      and basic buffer systems. In the presence of full thickness porcine buccal
      epithelium, ENI was unstable with only 23.4+/-15.7% intact drug present after 6
      h. The region responsible for this degradation was found to coincide with the
      major barrier region of the buccal epithelium as delineated through stability
      experiments in the presence of partial thickness buccal epithelium. Various
      peptidase inhibitors were used to isolate the enzyme(s) responsible for this
      degradation. Diprotin-A, a potent inhibitor of dipeptidyl peptidase IV, provided
      significant inhibition of the degradation of ENI in the presence of buccal
      epithelium. In vitro permeation studies revealed that the permeability
      coefficient of ENI across porcine buccal epithelium was 5.67+/-4.74x10(-7) cm/s.
      The enzymatic degradation of ENI was found not to be rate limiting to the drug's
      permeation across buccal epithelium, as diprotin-A did not increase the
      permeation of ENI. Sodium glycocholate as well as sodium taurocholate were also
      ineffective in enhancing the permeation of ENI across porcine buccal epithelium.

PMID- 11337058
TI  - A mechanism of the high frequency AC iontophoresis.
AB  - The efficiency and the voltage dependence of the AC iontophoresis were studied in
      vitro. Two cylindrical glass cells separated by a cellophane film were used,
      where the donor cell was filled with the solution of target electrolytes and the
      receptor cell with distilled water. The sinusoidal AC voltage with a frequency of
      1 kHz was applied between the two platinum plates located at the opposite ends of
      two cells. The time variation of the ion concentration was evaluated by measuring
      the impedance of the solution in the receptor cell. The transportation velocity
      of the ions increased with the amplitude of the voltage applied between two
      platinum plate electrodes apart 20 mm up to approximately 15 V, and leveled off
      above approximately 15 V. A theoretical model is proposed on the AC
      iontophoresis, where each ion moves together with the surrounding water molecules
      when it is hydrated. The effective Stokes radius of an ion is assumed to be half
      of the whole size of the ion with hydrating water molecules. When the external
      alternating electric field strongly vibrates the ion, the ion-dipole interactions
      between the ion and water molecules are broken, resulting in the reduced
      effective Stokes radius, which leads to the increase of the diffusion efficiency.

PMID- 11337059
TI  - LDL-induced association of anionic liposomes with cells and delivery of contents.
      II. Interaction of liposomes with cells in serum-containing medium.
AB  - In the present study we have investigated cell binding and drug delivery potency
      of various anionic liposomal formulations in a serum-supplemented growth medium,
      in order to understand the role of the LDL receptor in targeted drug delivery
      mediated by anionic liposomes. The cell lines used were CV1-P and CHO wild type,
      which both express the LDL receptor, and CHOldlA7, which lacks the LDL receptor.
      Cellular association of encapsulated methotrexate and fluorescein labeled
      phosphatidylethanolamine in the lipid bilayer was measured. Potency of two
      liposome-dependent drugs (N-phosphonacetyl-L-aspartic acid and fluoroorotic acid)
      was also measured by growth inhibition. Association of ePG liposomal aqueous
      contents with cells grown in serum-supplemented growth medium was up to 30-fold
      higher with CV1-P or CHO wild type cells than with CHOldlA7. Increased
      association was not paralleled by a corresponding increase in potency of liposome
      dependent drugs. The serum-dependent association of fluid, anionic (ePG)
      liposomes with cells expressing the LDL receptor is caused by an interaction of
      ePG liposomes with LDL. The failure of this association to increase drug delivery
      seems to be caused by the downregulation of LDL receptor expression when cells
      are continuously exposed to LDL.

PMID- 11337060
TI  - Fabrication of PLG microspheres with precisely controlled and monodisperse size
      distributions.
AB  - The size distribution of biodegradable polymer microspheres critically impacts
      the allowable routes of administration, biodistribution, and release rate of
      encapsulated compounds. We have developed a method for producing microspheres of
      precisely controlled and/or monodisperse size distributions. Our apparatus
      comprises spraying a polymer-containing solution through a nozzle with (i)
      acoustic excitation to produce uniform droplets, and (ii) an annular, non-solvent
      carrier stream allowing further control of the droplet size. We used this
      apparatus to fabricate poly(D,L-lactide-co-glycolide) (PLG) spheres. The acoustic
      excitation method, by itself, produced uniform microspheres as small as 30 microm
      in diameter in which > or =95% of the spheres were within 1.0-1.5 microm of the
      average. The carrier stream method alone allowed production of spheres as small
      as approximately 1-2 microm in diameter from a 100-microm diameter nozzle, but
      generated broader size distributions. By combining the two devices, we fabricated
      very uniform spheres with average diameters from approximately 5 to >500 microm.
      Furthermore, by discretely or continuously varying the experimental parameters,
      we fabricated microsphere populations with predefined size distributions.
      Finally, we demonstrate encapsulation and in vitro release of a model drug
      compound, rhodamine B. In summary, our apparatus provides unprecedented control
      of microsphere size and may allow development of advanced controlled-release
      delivery systems.

PMID- 11337061
TI  - Programmable biodegradable implants.
AB  - Pulsatile release implants were developed that release substances up to 58 days
      post implantation. With a cylindrical size of 2 mm diameter and 1.8 mm height the
      matrices can carry as much as 1 mg of drug and allow even for intracranial
      implantation into a rodent model. The matrices are made of materials that have
      been used for parenteral applications in humans before such as surface eroding
      polyanhydrides and bulk eroding poly(D,L-lactic acid) or poly(D,L-lactic acid-co
      glycolic acid). The onset of drug release is controlled by the degradation of
      bulk eroding polymers which are known to exhibit a certain stability over a
      defined period of time and which start eroding after they reach a critical degree
      of degradation. The time of drug release onset was found to depend on the
      molecular weight and the chemical state of the carboxylic acid end of the polymer
      chain. For testing the onset of release in vivo a nude mouse model was developed
      where the release of Evan's blue could be observed visually after subcutaneous
      application. By combining individual matrices with different release onset, a
      therapeutic system can be composed that releases drugs after implantation at
      predetermined time points in a preprogrammed way. Potential applications for such
      matrices is vaccination and local tumor therapy.

PMID- 11337062
TI  - New HPMA copolymers containing doxorubicin bound via pH-sensitive linkage:
      synthesis and preliminary in vitro and in vivo biological properties.
AB  - In this paper we describe the synthesis, physico-chemical characteristics and
      results of tests of biological activity of polymer drugs based on conjugates of
      anti-cancer drug doxorubicin (Dox) with water-soluble polymer drug carriers, N-(2
      hydroxypropyl)methacrylamide (HPMA) copolymers. In the conjugates the drug is
      attached to the polymer backbone via a spacer stable under physiological
      conditions (pH 7.4) and hydrolytically degradable in mild acidic environment
      (e.g., endosomes, pH approximately 5). This enables designing polymer drugs with
      long blood circulation and release and specific activation of the active compound
      in endosomes of target cells. Two types of Dox conjugates differing in the length
      and structure of the oligopeptide spacer were synthesised (GG and GFLG). In both
      types, the linkage susceptible to hydrolytic cleavage was formed by the reaction
      of the carbonyl group of Dox with the hydrazide group terminating the
      oligopeptide side chains of the polymer. In vitro incubation of conjugates in
      buffers resulted in much faster release of Dox from the polymer at pH 5 than at
      pH 7.4 (more than 10 times) the rate being higher for the conjugate containing GG
      spacer. The presence of cathepsin B in incubation media increased the rate of Dox
      release from the conjugate with GFLG spacer, Dox release from conjugate with GG
      spacer remained unchanged. Cytotoxicity of conjugates for T-splenocytes and mouse
      EL-4 T cell lymphoma cells was much higher compared with the effect of similar
      'classic' conjugates bearing Dox attached via amide bond. In vivo anti-tumor
      activity of conjugates containing hydrolytically sensitive linkage was also
      significantly improved in mouse EL4 T cell lymphoma.

PMID- 11337063
TI  - In vitro and in vivo evaluation of an oral system for time and/or site-specific
      drug delivery.
AB  - Aim of this work was the evaluation of an oral system (Chronotopic) designed to
      achieve time and/or site-specific release. The system consists in a drug
      containing core, coated by a hydrophilic swellable polymer which is responsible
      for a lag phase in the onset of release. In addition, through the application of
      an outer gastroresistant film, the variability in gastric emptying time can be
      overcome and a colon-specific release can be sought relying on the relative
      reproducibility of small intestinal transit time. For this study, cores
      containing antipyrine as the model drug were prepared by tableting and both the
      retarding and enteric coatings were applied in fluid bed. The release tests were
      carried out in a USP 24 paddle apparatus. The in vivo testing, performed on
      healthy volunteers, envisaged the HPLC determination of antipyrine salivary
      concentration and a gamma-scintigraphic investigation. The in vitro release
      curves presented a lag phase preceding drug release and the in vivo
      pharmacokinetic data showed a lag time prior to the detection of model drug in
      saliva. Both in vitro and in vivo lag times correlate well with the applied
      amount of the hydrophilic retarding polymer. The gamma-scintigraphic study
      pointed out that the break-up of the units occurred in the colon. The obtained
      results showed the capability of the system in delaying drug release for a
      programmable period of time and the possibility of exploiting such delay to
      attain colon-targeted delivery according to a time-dependent approach.

PMID- 11337064
TI  - An investigation into the effects of residual water on the glass transition
      temperature of polylactide microspheres using modulated temperature DSC.
AB  - The objective of the study was to ascertain residual water levels in polylactide
      and polylactide-co-glycolide microspheres prepared using the solvent evaporation
      technique and to investigate the effects of that water on the glass transitional
      behaviour of the microspheres. Microspheres were prepared from polylactic acid
      (PLA) and polylactide-co-glycolide (PLGA) 50:50 and 75:25 using a standard
      solvent evaporation technique. The glass transition was measured as a function of
      drying conditions using modulated temperature DSC. The microspheres were found to
      contain very low levels of dichloromethane, while residual water levels of up to
      circa 3% w/w were noted after freeze or oven drying, these levels being higher
      for microspheres containing higher glycolic acid levels. The residual water was
      found to lower the T(g) following the Gordon-Taylor relationship. The data
      indicate that the microparticles may retain significant water levels following
      standard preparation and drying protocols and that this drying may markedly lower
      the T(g) of the spheres.

PMID- 11337065
TI  - Comparative studies of H(2)O(2) detoxifying enzymes in green and greening barley
      seedlings under cadmium stress.
AB  - Cadmium(Cd) stress induced alterations in the activities of several
      representatives of the enzymatic antioxidant defense system such as guiacol
      peroxidase (POD), catalase (CAT) and ascorbate peroxidase (APX) were
      comparatively studied in green and greening barley seedlings that represent two
      different stages of plant development. Although roots were the main site of Cd
      accumulation, 1.5-3% of Cd was translocated into leaves and it induced oxidative
      damage which was indicated by the reduced chlorophyll and increased
      malondialdehyde content of the leaves. In roots of both types of seedlings
      exposed to various Cd concentrations, the APX activity was enhanced without any
      increase in the activity of POD. In leaves, however, elevated activities of both
      POD and APX could be observed. In roots of green seedlings at high concentration
      of Cd, the APX activity was reduced on the fourth day of culture but no
      inhibition was found in the POD activity. Leaf CAT which mainly represented the
      peroxisomal enzyme activity did not display any changes under Cd stress. Our
      results show that at both developmental stages barley seedlings exhibit a well
      defined activity of the enzymatic antioxidant system, which operates
      differentially in roots and shoots subjected to Cd stress.

PMID- 11337066
TI  - Salicylic acid response in rice: influence of salicylic acid on H(2)O(2)
      accumulation and oxidative stress.
AB  - We have studied the accumulation of hydrogen peroxide in rice leaves in response
      to salicylic acid (SA) treatment. H(2)O(2) accumulation was localized in the
      veins. While the activity of the H(2)O(2) degrading enzyme peroxidase was
      inhibited in response to SA, superoxide dismutase activity, which generates
      H(2)O(2), did not show any change. An increase in the activity of glutathione
      reductase, a peroxide degrading enzyme, was observed upon SA treatment, similar
      to the response reported by accumulation of active oxygen species. In rice leaves
      transformed with CaMV-GUS fusions, we found that SA treatment induced
      transcriptional activation through as-1 element. As-1 has been implicated in
      protective mechanisms that operate during some types of oxidative stress and the
      hypersensitive response (HR). Expression of rice pathogenesis-related protein 5
      (PR5), one of the PR genes associated with systemic acquired resistance, was
      induced by SA. This induction seems to be independent of the H(2)O(2)
      accumulation induced by SA. Inoculation of rice leaves with the rice blast
      fungus, Magneporthe grisea, also led to the accumulation of H(2)O(2) in the
      veins, suggesting the presence of common signals between SA and pathogen
      responses. Thus SA application seems to induce oxidative stress in rice through
      H(2)O(2); a signal molecule implicated in biotic and abiotic stress responses.

PMID- 11337067
TI  - Characterization of two Arabidopsis thaliana fructokinases.
AB  - Two different fructokinase isoforms of Arabidopsis thaliana have been identified
      and characterized by non-denaturing electrophoresis followed by activity
      staining. The two fructokinases, fructokinase1 (FRK1) and fructokinase2 (FRK2),
      showed a high specificity for fructose and did not stain when glucose or mannose
      were used as substrate. Fructose and ATP at high concentrations (above 5 mM)
      induced a substrate inhibition of the two enzymatic activities. Arabidopsis FRK1
      and FRK2 were capable of employing GTP, CTP, UTP and TTP as phosphate donors,
      although with a significantly lower efficiency than ATP. The two fructokinase
      activities were also activated by K(+), at around 10-20 mM, and inhibited by ADP
      and AMP at concentrations above 10 mM. Finally, FRK1 and FRK2 showed a different
      expression pattern in the plant, with FRK1 being more abundant in the roots and
      FRK2 in the shoots. The results demonstrate a simple technique that provides
      important information about fructokinase activities in the plants and which can
      be useful for the analysis of Arabidopsis mutants.

PMID- 11337068
TI  - Microsatellite markers from sugarcane (Saccharum spp.) ESTs cross transferable to
      erianthus and sorghum.
AB  - Analysis of a sugarcane (Saccharum spp.) EST (expressed sequence tag) library of
      8678 sequences revealed approximately 250 microsatellite or simple sequence
      repeats (SSRs) sequences. A diversity of dinucleotide and trinucleotide SSR
      repeat motifs were present although most were of the (CGG)(n) trinucleotide
      motif. Primer sets were designed for 35 sequences and tested on five sugarcane
      genotypes. Twenty-one primer pairs produced a PCR product and 17 pairs were
      polymorphic. Primer pairs that produced polymorphisms were mainly located in the
      coding sequence with only a single pair located within the 5' untranslated
      region. No primer pairs producing a polymorphic product were found in the 3'
      untranslated region. The level of polymorphism (PIC value) in cultivars detected
      by these SSRs was low in sugarcane (0.23). However, a subset of these markers
      showed a significantly higher level of polymorphism when applied to progenitor
      and related genera (Erianthus sp. and Sorghum sp.). By contrast, SSRs isolated
      from sugarcane genomic libraries amplify more readily, show high levels of
      polymorphism within sugarcane with a higher PIC value (0.72) but do not transfer
      to related species or genera well.

PMID- 11337069
TI  - Spatial distribution of photosynthetic response to long-term influence of
      elevated CO(2) in a mediterranean macchia mini-ecosystem.
AB  - During an open-top chamber experiment performed in evergreen 'macchia' ecosystem,
      which was represented by the clumps of natural vegetation dominated by Quercus
      ilex trees, the trees were exposed to one of two CO(2) concentrations (ambient
      CO(2), AC-variant and elevated CO(2), i.e. ambient plus 350 &mgr;mol CO(2) mol(
      1), EC-variant) continuously over 5 years. Clumps of natural vegetation were
      enclosed in open top chambers (OTCs). Within the crowns of investigated Quercus
      ilex trees in OTCs, two crown layers i.e. sunny (E-leaves) and shaded (S-leaves),
      were identified as differing in solar radiation environment. To evaluate the
      effect of elevated CO(2), as well as the functional differentiation in
      assimilation activity of E- versus S-leaves, gas exchange and chlorophyll &amacr;
      fluorescence techniques were used. The stimulatory effect of the long-term
      elevated CO(2) on the A(N)-PPFD relation was evident in E- and S-leaves of
      investigated Quercus trees. The A(Nmax) sensitivity of AC-variant leaves to the
      sudden application of elevated CO(2) was higher for S-leaves (42%) than for E
      leaves (24%). The PPFD saturated rate of regulated thermal energy dissipation
      (ERD) confirmed the foliage differentiation caused by the long-term influence of
      elevated CO(2). The ERD of E- and S-leaves in the AC-variant were 1.11 times of
      that in the EC-variant. However, the estimated rates of photochemistry (ERP) of E
      and S-leaves in the EC-variant were 1.35 and 1.22 times of E- and S-leaves in
      the AC-variant. The achievement of the critical value of q(P)=0.4 in E- and S
      leaves from the EC-variant under lower values of PPFD compared to the AC-variant
      indicates a higher degree of PSII over-reduction. Thus, elevated CO(2) can be
      responsible for an increased susceptibility of photosynthetic apparatus to high
      irradiance. The obtained results support the hypothesis on the foliage vertical
      distribution effect on the whole canopy response to elevated CO(2). The S-layers
      of the canopy can play an important role in providing storage space for
      photosynthesis under elevated CO(2).

PMID- 11337070
TI  - Ontogenic variations in n-alkanes during somatic embryogenesis of flax (Linum
      usitatissimum L.).
AB  - Hypocotyl segments (HS) of flax seedlings germinated in vitro, were used to
      induce indirect somatic embryogenesis on solid medium. The composition and
      distribution of n-alkanes in flax tissues collected at different developmental
      stages were studied by capillary gas chromatography (GC) and capillary gas
      chromatography-mass spectrometry (GC-MS). During induction and development of
      callus from hypocotyl tissues a decrease in the percentage of total lipids was
      observed. In all types of tissue sampled - HS used as primary explants, HS with
      differentiating calli at the cut ends (HSC), embryogenic (EC) and non-embryogenic
      calli (NEC) and somatic embryos (SE) - a skewed-normal distribution of n-alkanes
      with a low mass range (C(13)-C(21)) were found. The highest content of n-alkanes
      occurred in the primary hypocotyl explants and in the early stages of callus
      development. Longer carbon chain n-alkanes were observed only in the mature or
      differentiated tissues of hypocotyls and SE. Although the n-alkane contents
      decreased with time, in SE and calli, a significantly lower n-alkane content was
      observed in EC when compared to NEC independent of the time in culture. These
      results suggest the utilisation of n-alkanes for heterotrophic cellular growth as
      well as its mobilisation from EC to developing SE.

PMID- 11337071
TI  - Are hyperhydric shoots of Prunus avium L. energy deficient?
AB  - The content of oxidized and reduced pyridine nucleotides and some enzymatic
      activities of the oxidative pentose phosphate and glycolytic pathways were
      compared in normal (NS, growing on agar) and hyperhydric (HS, growing on gelrite)
      shoots of Prunus avium L. after 4 weeks of in vitro culture. The chlorophyll
      fluorescence from leaves and the redox capacity of the plasma membrane (reduction
      of exogenously added ferricyanide) of both types of shoots were recorded. The
      pool of oxidized and reduced pyridine nucleotides was lower in HS than in NS.
      These results suggested a reduced metabolism of HS in comparison to normal ones.
      This hypothesis was also supported by other observations. First, chlorophyll
      fluorescence measurements showed a lower chlorophyll content and a slight
      reduction of the photosynthetic capacity in HS. Second, the low activity of some
      enzymes of oxidative pentose phosphate pathway (OPP) and glycolysis indicated a
      decline of these biochemical pathways in HS with the consequence of a reduced
      production of chemical energy in the form of NAD(P)H and ATP. Finally, the lower
      reduction of ferricyanide by HS suggested a lower rate of redox reactions at the
      level of the plasma membrane of these shoots in comparison to NS.

PMID- 11337072
TI  - Relationship between tomato fruit growth and fruit osmotic potential under
      salinity.
AB  - To investigate the relationship between fruit growth and fruit osmotic potential
      (Psi(s)) in salty conditions, a sensitive tomato cultivar (Lycopersicon
      esculentum Mill.) and a tolerant accession of the wild species Lycopersicon
      pimpinellifolium Mill. were grown in a greenhouse with 0 and 70 mM NaCl, and the
      growth of the fruit studied from 15 to 70 days after anthesis (DAA). L.
      pimpinellifolium did not reduce significantly fruit weight in salty conditions
      throughout the growth period, whereas L. esculentum fruit weights decreased
      significantly with salinity from 45 DAA. L. esculentum fruit fresh weight
      reductions resulted from both less dry matter and water accumulation, although
      the fruit water content was affected by salinity before the fruit weight. In both
      species, fruit osmotic potential (Psi(s)) decreased significantly with salinity
      during the rapid fruit growth phase, although the changes were different. Thus,
      fruits from L. pimpinellifolium salt treated plants showed a Psi(s) reduction at
      the beginning (15 DAA) twice as high as that found in L. esculentum. As the
      advanced growth stage (from 15 to 55 DAA), the Psi(s) reduction percentages
      induced by salinity were quite similar in L. pimpinellifolium fruits, while
      increased in L. esculentum. Under saline conditions, the solutes contributing to
      reduce the fruit Psi(s) during the first 55 DAA were the inorganic solutes in
      both species, while in the ripe fruits they were hexoses. L. esculentum fruits
      accumulated K(+) as the main osmoticum in salty conditions, while L.
      pimpinellifolium fruits were able to use not only K(+) but also the Na(+)
      provided by the salt.

PMID- 11337073
TI  - Effects of desiccation on photosynthesis pigments and the ELIP-like dsp 22
      protein complexes in the resurrection plant Craterostigma plantagineum.
AB  - Desiccation and abscisic acid treatment lead to major changes in thylakoid
      membranes of the desiccation-tolerant plant Craterostigma plantagineum. The
      chlorophyll contents and proteins of the light harvesting complexes decrease
      during desiccation, although some chlorophyll is retained in the dehydrated
      state. The xanthophyll cycle pigment zeaxanthin, however, increased. Under these
      conditions, a 22 kDa ELIP-like desiccation-induced protein (dsp 22) accumulated
      in the thylakoid membranes. Fractionation of pigment-protein complexes of
      stressed plants revealed that the dsp 22 protein co-localized with the carotenoid
      zeaxanthin. Inhibition of zeaxanthin production had a negative effect on the
      accumulation of the dsp 22 protein. It is suggested that dsp 22 contributes to
      the protection against photoinhibition caused by dehydration.

PMID- 11337074
TI  - Chloroplast fructose-1,6-bisphosphatase from Oryza differs in salt tolerance
      property from the Porteresia enzyme and is protected by osmolytes.
AB  - Salinity exerted a distinctly differential effect on fructose-1,6-bisphosphatase
      (EC. 3.1.3.11) isolated from salt-sensitive and salt-tolerant rice (Oryza sativa)
      varieties. Cytosolic and chloroplastic isoforms of the enzyme from salt-sensitive
      rice seedlings exhibited decreased catalytic activity during growth in the
      presence of salt. Furthermore, chloroplastic fructose 1,6-bisphosphatase purified
      from salt-sensitive (O. sativa cv. IR26) and from the wild halophytic rice
      Porteresia coarctata differed in their in vitro salt tolerance property although
      they exhibited otherwise identical biochemical and immunological properties. This
      decline in enzyme activity was not correlated with de novo synthesis of the
      chloroplastic fructose-1,6-bisphosphatase protein in the presence of salt. The
      inhibitory effect of increasing concentration of NaCl on in vitro enzymatic
      activity could be prevented by preincubation of the enzyme with a number of
      osmolytes with an effectiveness in the order polyol>sugars. Further, the
      intrinsic tryptophan fluorescence of the purified rice enzyme is altered in vitro
      with increasing NaCl concentration which could be prevented by preincubation with
      inositol. Purified chloroplastic fructose-1.6-bisphosphatase from P. coarctata
      however, exhibits no such inhibition of enzyme activity in vitro or alteration in
      tryptophan fluorescence with increasing NaCl concentration.

PMID- 11337075
TI  - Triiodobenzoic acid, an auxin polar transport inhibitor, suppresses somatic
      embryo formation and postembryonic shoot/root development in Eleutherococcus
      senticosus.
AB  - The effect of auxin polar transport inhibitor on somatic embryo development and
      postembryonic growth in Siberian ginseng (Eleutherococcus senticosus) was
      examined. In the presence of 2,3,5-triiodobenzoic acid (TIBA), an auxin polar
      transport inhibitor, embryo formation from embryogenic cells was suppressed,
      while cell division was not affected. When globular embryos at different stages
      were transferred onto medium containing TIBA, development of axial and bilateral
      polarity was suppressed in a stagespecific manner. In abnormal embryos induced by
      TIBA, further development of shoot and root apical meristems and vascular
      differentiation was also suppressed. Thus, abnormal development of embryos
      induced by inhibition of auxin polar transport resulted in plantlets without
      shoots and roots.

PMID- 11337076
TI  - Excess cation uptake, and extrusion of protons and organic acid anions by Lupinus
      albus under phosphorus deficiency.
AB  - In symbiotically-grown legumes, rhizosphere acidification may be caused by a high
      cation/anion uptake ratio and the excretion of organic acids, the relative
      importance of the two processes depending on the phosphorus nutritional status of
      the plants. The present study examined the effect of P deficiency on extrusions
      of H(+) and organic acid anions (OA(-)) in relation to uptake of excess cations
      in N(2)-fixing white lupin (cv. Kiev Mutant). Plants were grown for 49 days in
      nutrient solutions treated with 1, 5 or 25 mmol P m(-3) Na(2)HPO(4) in a
      phytotron room. The increased formation of cluster roots occurred prior to a
      decrease in plant growth in response to P deficiency. The number of cluster roots
      was negatively correlated with tissue P concentrations below 2.0 g kg(-1) in
      shoots and 3 g kg(-1) in roots. Cluster roots generally had higher concentrations
      of Mg, Ca, N, Cu, Fe, and Mn but lower concentrations of K than non-cluster
      roots. Extrusion of protons and OA(-) (90% citrate and 10% malate) from roots was
      highly dependent on P supply. The amounts of H(+) extruded per unit root biomass
      decreased with time during the experiment. On the equimolar basis, H(+) extrusion
      by P-deficient plants (grown at 1 and 5 mmol P m(-3)) were, on average, 2-3-fold
      greater than OA(-) exudation. The excess cation content in plants was generally
      the highest at 1 mmol P m(-3) and decreased with increasing P supply. The ratio
      of H(+) release to excess cation uptake increased with decreasing P supply. The
      results suggest that increased exudation of OA(-) due to P deficiency is
      associated with H(+) extrusion but contributes only a part of total
      acidification.

PMID- 11337077
TI  - Integration and expression of Sorghum C(4) phosphoenolpyruvate carboxylase and
      chloroplastic NADP(+)-malate dehydrogenase separately or together in C(3) potato
      plants(1).
AB  - We have integrated two cDNAs expressing Sorghum photosynthetic
      phosphoenolpyruvate carboxylase (C(4)-PEPC) and NADP-malate dehydrogenase
      (cpMDH), two key enzymes involved in the primary carbon fixation pathway of NADP
      malic enzyme-type C(4) plants, separately or together into a C(3) plant (potato).
      Analysis of the transgenic plants showed a 1.5-fold increase in PEPC and cpMDH
      activities compared to untransformed plants. Immunolocalization confirmed an
      increase at the protein level of these two enzymes in the transgenic plants and
      indicated that the Sorghum cpMDH was specifically addressed to the chloroplasts
      of potato mesophyll cells. However, integration of either or both of the cDNAs
      into the potato genome did not appear to significantly modify either tuber starch
      grain content or the rate of photosynthetic O(2) production compared to control
      untransformed plants. The low level of transgene expression probably explains the
      lack of influence on carbon metabolism and photosynthetic rates. This general
      observation suggests that some complex mechanism may regulate the level of
      production of foreign C(4) metabolism enzymes in C(3) plants.

PMID- 11337078
TI  - Carrageenan oligosaccharides enhance stress-induced microspore embryogenesis in
      Brassica oleracea var. italica.
AB  - Embryogenic induction in cultures of isolated microspores is a stress-dependent
      process, which can be triggered by heat shock, sucrose or nitrogen starvation or
      by anti-microtubular drugs. As they are known to mimic biotic stress,
      oligosaccharides were tested as an alternative source of compounds to induce
      microspore embryogenesis in Brassica oleracea var. italica. Among the eight
      oligosaccharide series that were investigated and the corresponding
      polysaccharides, namely pectin, alginate, fucan, laminarin, agar and kappa-, iota
      , and lambda-carrageenans, only the carrageenan oligomers displayed significant
      effects on microspore induction. When supplied in combination to heat stress,
      they markedly enhanced the final yields of microspore-derived embryos, with a two
      fold increase in the most reactive treatment, i.e. in the presence of lambda
      carrageenan oligosaccharides. A 30 min treatment was enough to stimulate
      embryogenesis, and two optimal concentrations were observed, 170 nM and 34
      &mgr;M.

PMID- 11337079
TI  - Plant regeneration from cell suspension-derived protoplasts of Primula malacoides
      and Primula obconica.
AB  - Protoplasts were isolated from cell suspension cultures of Primula malacoides cv.
      'Lovely Tokyo' and P. obconica cv. 'Aalsmeer Giant White'. P. obconica
      protoplasts were embedded in 0.1% (w/v) gellan gum-solidified discs comprising MS
      medium supplemented with 3 mg/l of 2,4-D or picloram, 0.1 mg/l of zeatin, 0.2 M
      glucose and 0.2 M mannitol, and surrounded by a liquid medium of the same
      composition except for the addition of 0.1% (w/v) activated charcoal. The
      protoplasts formed visible colonies, which were transferred to the regeneration
      medium containing 30 g/l of sucrose, 0.1 mg/l of picloram and 2 mg/l of zeatin
      for shoot induction. P. malacoides protoplasts formed visible colonies when
      cultured in disc culture using 0.1% (w/v) gellan gum-solidified MS medium
      containing 5 mg/l of 2,4-D, 1 mg/l of NAA, 0.1 mg/l of zeatin and 0.4 M glucose.
      Small calli were transferred to MS medium supplemented with 5 mg/l of zeatin for
      shoot regeneration. The shoots of both species readily rooted on plant growth
      regulator-free 1/2 MS medium and successfully acclimatized to greenhouse
      conditions. The protoplast-derived plants showed some alterations in
      morphological characteristics from those of the in-vitro-germinated control
      plants.

PMID- 11337080
TI  - Polyamines as biomarkers for plant regeneration capacity: improvement of
      regeneration by modulation of polyamine metabolism in different genotypes of
      indica rice.
AB  - The importance of cellular polyamine (PA) levels and the ratio of putrescine
      (Put) to spermidine (Spd) for plant regeneration ability via somatic
      embryogenesis in several commercially grown indica rice varieties is reported
      here. The genotypes namely NDR-624, IR-20, IR-36, BJ-1 (having Put:Spd ratio
      approximately 2.3) showed superior plant regeneration while KL, PB-1 and TN-1
      (having Put:Spd ratio approximately 3.8) showed moderate plant regeneration
      ability. The genotypes namely HS, Bindli, DV-85, ACB-72, IR-64 and IR-72 (having
      Put:Spd ratio approximately 5.0) showed poor plant regeneration ability. In
      contrast KH-7 (Put:Spd ratio approximately 10.0) showed no response at all.
      Favorable modification of cellular PA titers and their Put:Spd ratio by the
      addition of exogenous PAs (Put, Spd) or their biosynthesis inhibitor,
      difluoromethylarginine (DFMA) led to the induction/promotion of plant
      regeneration in poorly responding genotypes. These results showed a close
      relationship between cellular PA levels and their Put:Spd ratio with in vitro
      morphogenetic capacity in indica rice and suggest that the cellular PAs and
      Put:Spd ratios are important determinants (biomarkers) of plant regeneration
      ability in indica rice, and the improvement/induction of plant regeneration in
      morphogenetically poor and recalcitrant species could be achieved by modulating
      PA metabolism.

PMID- 11337081
TI  - Elevated sensitivity to gibberellin by vernalization in the vegetative rosette
      plants of Eustoma grandiflorum and Arabidopsis thaliana.
AB  - Changes in the sensitivity to gibberellin (GA) after vernalization were studied
      in the vegetative rosette of Eustoma grandiflorum and late flowering Arabidopsis
      thaliana mutant, fca-1. The sensitivity to GA after vernalization was monitored
      using the bolting rate of plants that were grown on a medium containing GA(3) or
      ancymidol. The bolting rates were higher in vernalized plants than non-vernalized
      plants when the same GA(3) concentration was used. There was a positive
      relationship between the duration of vernalization and the bolting rate in E.
      grandiflorum. In contrast, a negative relationship between the duration of
      treatment and bolting rate was found in the non-vernalized plants. In fca-1, the
      flowering time of vernalized plants was significantly reduced compared with the
      non-vernalized plants under various concentrations of GA(3) treatment. To
      elucidate whether this elevated sensitivity relates to the efficiency of GA
      signal transduction, we measured the transcript amounts of Expansin (Exp), which
      is up-regulated by GA, and GA20-oxidase (GA20ox) and GA3 beta-hydroxylase
      (GA3betahy), which are down-regulated by GA. The transcript amounts were
      estimated using the Taq-Man PCR system based on combinations of primers and
      probes that specifically detect the genes, and normalized by the transcript
      amount of ubiquitin gene measured as an internal standard. For each concentration
      of GA treatments examined, Expansin of both E. grandiflorum and A. thaliana was
      induced at a higher rate in the vernalized plants than in the non-vernalized
      plants. The expression of GA20ox and GA3betahy of E. grandiflorum decreased
      faster in the vernalized plants than the non-vernalized plants. We conclude that
      vernalization is a critical environmental cue not only for initiating GA
      biosyntheses in vegetative rosette, but also for elevating the GA sensitivity of
      the plants via a GA signal transduction pathway.

PMID- 11337083
TI  - Regulation of corticotropin-releasing hormone in vitro.
AB  - Studies examining regulation of corticotropin-releasing hormone (CRH) in vitro
      have been used to validate findings obtained in vivo and more importantly have
      been used as model systems to better understand signalling mechanisms responsible
      for the expression of the CRH gene and peptide. Most in vitro studies examining
      CRH have utilized hypothalamic tissue while a few have focused on the amygdala.
      Furthermore, clonal cell lines have also been utilized as models of central
      nervous system CRH neurons. Stimuli that have been implicated in regulating
      hypothalamic CRH in vitro include protein kinase A (PKA) and protein kinase C
      (PKC) activators, glucocorticoids, biogenic amines, cytokines and the gaseous
      neurotransmitters. CRH levels in the amygdala in vitro are affected by some of
      the same stimuli that regulate hypothalamic CRH; however there is evidence
      supporting differential regulation of CRH in these two brain regions by some of
      the same stimuli. Only a few studies in aggregate have investigated the signal
      transduction mechanisms responsible for CRH expression. These mechanistic studies
      have focused on PKA- and glucocorticoid-mediated changes in CRH expression.
      Clearly much more investigative work in better understanding CRH regulation in
      vitro is needed.

PMID- 11337084
TI  - The role of CRH in behavioral responses to stress.
AB  - Corticotropin-releasing hormone (CRH) and urocortin in the central nervous system
      affect behavior and can enhance behavioral responses to stressors. The action of
      CRH-related peptides is mediated through multiple receptors that differ markedly
      in their pharmacological profiles and anatomical distribution. Comparative
      pharmacology of CRH receptor agonists suggests that CRH, urocortin, sauvagine and
      urotensin consistently mimic, and CRH receptor antagonists consistently lessen,
      functional consequences of stressor exposure. Recently, important advances have
      been made in understanding the CRH system and its role in behavioral responses to
      stress by the development of specific CRH receptor antagonists, application of
      antisense oligonucleotides and development of transgenic mice lacking peptides
      and functional receptors. This review summarizes recent findings with respect to
      components of the CRH system and their role in stress-induced behavioral
      responses.

PMID- 11337085
TI  - The physiology of corticotropin-releasing hormone deficiency in mice.
AB  - A review of the generation and characterization of corticotropin-releasing
      hormone (CRH)-deficient mice is presented. The studies summarized demonstrate the
      central role of CRH in the pituitary-adrenal axis response to stress, circadian
      stimulation, and glucocorticoid withdrawal. Additionally, pro-inflammatory
      actions of CRH at sites of local inflammation are given further support. In
      contrast, behavioral effects during stress that had been ascribed to CRH action
      are not altered in CRH-deficient mice. The normal behavioral response to stress
      in CRH-deficient mice strongly suggests the importance of other, possibly as yet
      undiscovered, CRH-like molecules.

PMID- 11337087
TI  - Mouse models of altered CRH-binding protein expression.
AB  - CRH is the key physiological mediator of the endocrine, autonomic, and behavioral
      responses to stress. The recent characterization of urocortin, a new mammalian
      CRH-like ligand, adds to the complexity of the CRH system. Both CRH and urocortin
      mediate their endocrine and/or synaptic effects via two classes of CRH receptors.
      Similarly, both CRH and urocortin bind to the CRH-binding protein (CRH-BP). This
      secreted binding protein is smaller than the CRH receptors, but binds CRH and
      urocortin with an affinity equal to or greater than that of the receptors, and
      blocks CRH-mediated ACTH release in vitro. Several regions of CRH-BP expression
      colocalize with sites of CRH synthesis or release, suggesting that this binding
      protein may have a profound impact on the biological activity of CRH (or
      urocortin). While in vitro and in vivo studies have characterized the biochemical
      properties and regulation of the CRH-BP, animal models of altered CRH-BP
      expression can provide additional information on the in vivo role of this
      important modulatory protein. This review focuses on three mouse models of CRH-BP
      overexpression or deficiency. These animal models show numerous physiological
      changes in the HPA axis and in energy balance, with additional alterations in
      anxiogenic behavior. These changes are consistent with the hypothesis that CRH-BP
      plays an important in vivo modulatory role by regulating levels of "free" CRH and
      other CRH-like peptides in the pituitary and central nervous system.

PMID- 11337086
TI  - Animal models of CRH excess and CRH receptor deficiency display altered
      adaptations to stress.
AB  - This review highlights new information gained from studies using recently
      developed animal models that harbor specific alterations in corticotropin
      releasing hormone (CRH) pathways. We discuss features of a transgenic mouse model
      of chronic CRH overexpression and two mouse models that lack either CRH receptor
      type 1 (CRH-R1) or type 2 (CRH-R2). Together these models provide new insights
      into the role of CRH pathways in promoting stability through adaptive changes, a
      process known as allostasis.

PMID- 11337088
TI  - Molecular biology of the CRH receptors-- in the mood.
AB  - Dysfunctioning of corticotropin-releasing hormone (CRH) and its receptors (CRH(1)
      and CRH(2)) has been linked to the development of stress-related disorders, such
      as mood and eating disorders. The molecular characterization of CRH(1) and CRH(2)
      receptors and their splice variants has generated detailed information on their
      pharmacology, tissue distribution and physiology. While mammalian CRH(1)
      receptors nonselectively bind CRH analogs, the ligand specificity of CRH(2) is
      narrower. CRH(1) receptors are predominantly expressed in the brain and
      pituitary, whereas CRH(2) receptor expression is limited to particular brain
      areas and to some peripheral organs. Molecular approaches to block CRH(1)
      receptor expression in the brain argue in favor of its involvement in the
      regulation of some aspects of the stress response. The CRH(2alpha) receptor may
      be more important for motivational types of behavior essential for survival, such
      as feeding and defense.(1)

PMID- 11337089
TI  - Corticotropin-releasing hormone and its receptors; an evaluation at the
      transcription level in vivo.
AB  - Activation of the hypothalamic-pituitary-adrenal (HPA) axis is the main defining
      feature of the stress response. The primary mediator of this response is
      corticotropin-releasing hormone (CRH), a 41-residue peptide acknowledged as the
      principal hypophysiotropic factor driving stress-induced adrenocorticotropic
      hormone (ACTH) secretion. Although CRH is widely distributed within the central
      nervous system (CNS), the paraventricular nucleus (PVN) of the hypothalamus is
      the principal site of the parvocellular neurosecretory neurons responsible for
      delivering CRH to the hypophyseal portal system, an event that initiates the
      activity of the pituitary-adrenal axis. Stress-induced transcriptional activation
      of CRH takes place quite uniquely in this hypothalamic nucleus, despite the
      robust constitutive hybridization signal for CRH mRNA across the brain. The fact
      that CRH itself is capable of mimicking these effects and that de novo but
      transient expression of its type one receptor occurs in the PVN are data that
      make this hypothalamic region of great interest to study the mechanisms that lead
      to such specific transcriptional activity. This review will present evidence of
      such phenomenon by stressors of different categories as well as the possible
      neuromediators involved.

PMID- 11337090
TI  - Regulation of pituitary corticotropin releasing hormone receptors.
AB  - Corticotropin releasing hormone (CRH) stimulates pituitary ACTH secretion through
      type-1 CRH (CRH1) receptors. Stimulation of the hypothalamic pituitary adrenal
      (HPA) axis as well as increased corticotroph responsiveness during stress and
      adrenalectomy are associated with marked pituitary CRH binding downregulation.
      The presence of CRH1 receptors in the pituitary are essential to maintain ACTH
      secretion. Downregulation of CRH binding is associated with normal or elevated
      levels of CRH1 receptor mRNA and this may contribute to the maintainence of
      permissive levels of CRH1 receptors in the pituitary. Injection of either CRH or
      glucocorticoids in rats in vivo induces CRH binding and CRH1 receptor mRNA
      downregulation, whereas their simultaneous administration causes only transient
      CRH1 receptor mRNA loss. Vasopressin increases CRH1 receptor mRNA levels. This
      suggest that interactions between CRH, vasopressin and glucocorticoids accounts
      for CRH1 receptor mRNA upregulation during stress. The lack of correlation
      between CRH binding and CRH1 receptor mRNA indicates that the major sites for
      pituitary CRH1 receptor regulation are at the post-transcriptional level.

PMID- 11337091
TI  - Corticosterone modulation of ACTH secretogogue gene expression in the
      paraventricular nucleus.
AB  - This review will describe effects of corticosterone on the temporal dynamics of
      components within the hypothalamo-pituitary-adrenal (HPA) axis in response to
      sustained hypovolemia. The characterization of the synthetic and secretory
      profiles of HPA elements in these rat models reveals the complexities of steroid
      mediated regulation of neuroendocrine and corticotrope function during a
      sustained stress event. Collectively, our data suggest activation of gene
      transcription and secretion are independently controlled, and that corticosterone
      affects adrenocorticotropin hormone (ACTH) gene expression in the parvicellular
      neuroendocrine part of the hypothalamic paraventricular nucleus using two
      mechanisms: first, an inhibition which contributes to classic negative feedback,
      and second, a facilitation, which is seen at low plasma concentrations.

PMID- 11337092
TI  - Endometrial and myometrial corticotropin-releasing hormone (CRH): its regulation
      and possible roles.
AB  - In human endometrium, both epithelial and stroma cells produce corticotropin
      releasing hormone (CRH). Both types of cells also possess specific CRH-binding
      sites indicating a local effect of endometrial CRH. The transcription of the CRH
      gene in human endometrium is under the control of steroid hormones and locally
      produced prostanoids and interleukins. Endometrial CRH interacts with locally
      produced prostaglandins and interleukins. Based on these observations it can be
      hypothesized that CRH, prostaglandins and interleukins form a network responsible
      for the communication between epithelial and stromal cells, at the level of the
      endometrium, and between endometrial and myometrial cells at the level of uterus.
      The net product of these interaction is the micro-regulation of the decidualizing
      process and the preparation of endometrium for the implantation/nidation of the
      conceptus. Indeed, this network may represent the core of the intrauterine
      neuroendocrine-immune interactions involved in the decidualization of stroma and
      implantation of blastocyst. In addition, this network appears to be essential for
      the fine-tuning of myometrial tone.

PMID- 11337093
TI  - The regulation of human corticotrophin-releasing hormone gene expression in the
      placenta.
AB  - Corticotrophin-releasing hormone (CRH) is a 41 amino acid neuropeptide that is
      expressed in the hypothalamus and the human placenta. Placental CRH production
      has been linked to the determination of gestational length in the human. Although
      encoded by a single copy gene, CRH expression in the placenta is regulated
      differently to the hypothalamus. Glucocorticoids stimulate CRH promoter activity
      in the placenta but inhibit it's activity in the hypothalamus, via mechanisms
      involving different regions of the CRH promoter. We discuss how various stimuli
      alter CRH promoter activity and why these responses are unique to the placenta.

PMID- 11337094
TI  - CRH in chronic inflammatory stress.
AB  - Corticotropin-releasing hormone (CRH) is an important regulator of inflammation
      at the central level through hypothalamo-pituitary-adrenal (HPA) axis control of
      glucocorticoid secretion. Integrity of the HPA axis during autoimmune disease is
      critical in controlling the severity of inflammation, but the evidence for an HPA
      axis defect in the etiology of autoimmune diseases is not compelling. CRH
      secreted from leukocytes and neuronal terminals in peripheral tissues also plays
      a role in mediating inflammation. Elucidating the pathways underlying the
      expression of CRH, both central and peripheral, and interactions of CRH with
      other inflammatory mediators such as substance P, confers great potential for the
      development of a new generation of anti-inflammatory agents.

PMID- 11337095
TI  - Peripheral corticotropin-releasing hormone and urocortin in the control of the
      immune response.
AB  - Immunological and cellular stress signals trigger the release of corticotropin
      releasing hormone (CRH) from the spleen, thymus and inflamed tissue. In vivo and
      in vitro studies generally suggest that peripheral, immune CRH has pro
      inflammatory effects and acts in a paracrine manner by binding to CRH-R1 and CRH
      R2 receptors on neighboring immune cells. However, it now seems likely that some
      of the suggested pro-inflammatory actions of CRH may be attributed to novel CRH
      like peptides or to the related peptide, urocortin, which is also present in
      immune cells and has especially high affinity for CRH-R2 receptors.

PMID- 11337096
TI  - Cardiovascular actions of CRH and urocortin: an update.
AB  - Urocortin is a potent regulator of cardiac function, with actions that are
      prolonged in experimental animals. These changes are mediated via binding to CRH
      receptors found in peripheral tissues. The diversity of actions of urocortin on
      behaviour, appetite, inflammation and the cardiovascular system suggest that this
      peptide may be an endogenous factor mediating actions previously attributed to
      CRH. The present review will focus on the recent understanding of mechanisms
      mediating the cardiovascular actions of urocortin and CRH reported to date.

PMID- 11337097
TI  - Pretreatment with glucose increases entry of urocortin into mouse brain.
AB  - Although urocortin is a potent inhibitor of food ingestion after peripheral
      administration, it was recently shown that under normal conditions this peptide
      crosses the blood-brain barrier (BBB) at a very slow rate. We examined whether
      hyperglycemia could stimulate the rate of entry (K(i)) of (125)I-urocortin into
      the mouse brain. In euglycemic mice, (125)I-urocortin injected iv entered the
      brain at a rate similar to that of the vascular marker (99m)Tc-albumin. However,
      injection of glucose (3 g/kg, ip) 0.5, 1, or 2 h before the (125)I-urocortin
      greatly increased the influx of urocortin. Without the glucose, the self
      inhibition characteristic of a saturable transport system was not apparent. Self
      inhibition could be demonstrated after the glucose injection, indicating
      activation of a transport system for urocortin that was saturable. Injection of
      insulin (10 U/kg, ip) 1 or 2 h before the (125)I-urocortin decreased the K(i).
      Thus, the entry of urocortin into brain can be activated by changes in the
      concentration of blood glucose, illustrating the responsiveness of the BBB to
      regulatory influences.

PMID- 11337098
TI  - Hyperactivity of CRH neuronal circuits as a target for therapeutic interventions
      in affective disorders.
AB  - Increasing evidence suggests that the neuroendocrine changes seen in psychiatric
      patients, especially in those suffering from affective disorders, may be causally
      related to the psychopathology and course of these clinical conditions. The most
      robustly confirmed neuroendocrine finding among psychiatric patients with
      affective disorders is hyperactivity of the hypothalamic-pituitary-adrenocortical
      (HPA) system, resulting from hyperactive hypothalamic corticotropin-releasing
      hormone (CRH) neurons. A large body of preclinical and clinical evidence suggests
      that both genetic and environmental factors contribute to the development of
      these HPA system abnormalities. Further, normalization of HPA system regulation
      was shown to be a prerequisite for favorable treatment response and stable
      remission among depressives. Preclinical data based on animal models including
      selectively bred rat lines and mouse mutants support the notion that CRH neurons
      are hyperactive also in neuroanatomical regions that are involved in behavioral
      regulation but are located outside the neuroendocrine system. This raises the
      question of whether more direct interventions such as CRH receptor antagonists
      would open a new lead in the treatment of stress-related disorders such as
      depression, anxiety and sleep disorders. Recent clinical observations support
      this possibility.

PMID- 11337099
TI  - Corticotropin-releasing hormone in depression and post-traumatic stress disorder.
AB  - Corticotropin-releasing hormone (CRH) has been implicated in the regulation of a
      wide range of behaviors including arousal, motor function, feeding, and
      reproduction. Because depressed patients are often hypercortisolemic and
      intracerebroventricular administration of CRH to experimental animals produces a
      syndrome reminiscent of depression, dysregulation of this compound has been
      suggested to be involved in the pathogenesis of depressive and anxiety disorders.
      Studies of cerebrospinal fluid CRH levels and clinical neuroendocrine tests in
      patients with anxiety and affective disorders have supported this hypothesis.
      This review discusses these neuroendocrine findings in melancholic and atypical
      depression as well as post-traumatic stress disorder (PTSD). Overall, the data
      suggest that melancholic depression is characterized by hyperactive central CRH
      systems with overactivity of the pituitary-adrenal (HPA) axis. On the other hand,
      atypical depression is characterized by hypoactive central CRH systems and
      accompanying underactivity of the hypothalamic-pituitary-adrenal axis.
      Furthermore, the neuroendocrinology of PTSD appears to be unique, in that
      patients have hyperactive central CRH systems with underactivity of the pituitary
      adrenal axis.

PMID- 11337100
TI  - LUMO energy of model compounds of bispyridinium compounds as an index for the
      inhibition of choline kinase.
AB  - Eleven derivatives of 1,1'-[1,2-ethylenebis(benzene-1,4-diylmethylene)]bis(4
      pyridinium) dibromides bearing various groups at C-4 of the pyridinium moiety
      were synthesized and examined for their inhibition of choline kinase (ChoK) and
      antiproliferative activities. The C-4 substituents include electron-releasing,
      neutral or electron-withdrawing groups. A one-parameter regression equation has
      been derived which satisfactorily describes the ex vivo inhibitory potency of
      ChoK of the title compounds. The electronic effect plays a critical function in
      the ex vivo inhibition of ChoK although the role of electrostatic interactions
      could be altered due to a solvation process of both ChoK and ligands.

PMID- 11337101
TI  - Synthesis, anticonvulsant properties and pharmacokinetic profile of novel 10,11
      dihydro-10-oxo-5H-dibenz/b,f/azepine-5-carboxamide derivatives.
AB  - A series of novel derivatives of oxcarbazepine (5), 10,11-dihydro-10-oxo-5H
      dibenz/b,f/azepine-5-carboxamide was synthesised and evaluated for their
      anticonvulsant activity and sodium channel blocking properties. The oxime 8 was
      found to be the most active compound from this series, displaying greater potency
      than its geometric isomer 9 and exhibiting also the highest protective index
      value. Importantly, the metabolic profile of 8 differs from the already
      established dibenz/b,f/azepine-5-carboxamide drugs such as 1 and 5 which undergo
      rapid and complete conversion in vivo to several biologically active metabolites.
      In contrast 8 is metabolised to only a very minor extent leading to the
      conclusion that the observed anti-convulsant effect is solely attributable to 8.
      It is concluded that 8 may be as effective as 1 and 5 at controlling seizures and
      that the low toxicity and consequently high protective index should provide the
      compound with an improved side-effect profile.

PMID- 11337102
TI  - Synthesis and antifolate evaluation of the aminopterin analogue with a bicyclo.
AB  - N-[4-[[2,4-diamino-6-pteridinyl)methyl]amino]bicyclo[2.2.2]octane-1-carbonyl]-L
      glutamic acid (1) was synthesized and tested for antifolate activity. N-(4
      Aminobicyclo[2.2.2]octane-1-carbonyl-L-glutamic acid dimethyl ester (6), the side
      chain precursor to subject compound 1, was synthesized readily via reported
      bicyclo[2.2.2]octane-1,4-dicarboxylic acid monoethyl ester (2). The side chain
      precursor 6 was alkylated by 6-(bromomethyl)-2,4-pteridinediamine (7). Subsequent
      ester hydrolysis then afforded 1. Antifolate and antitumor evaluation of 1 verses
      L1210 dihydrofolate reductase (DHFR) and three tumor cell lines (L1210, S180, and
      HL60) showed it to be ineffective. Although compound 1 was very similar to
      aminopterin structurally, the bicyclo[2.2.2]octane ring system in place of the
      phenyl ring in the p-aminobenzoate moiety effectively negates the stoichiometric
      binding displayed by many classical DHFR inhibitors bearing appropriate aromatic
      ring systems in the side chain.

PMID- 11337103
TI  - Synthesis and biological evaluation of some novel 4H-benzopyran-4-one derivatives
      as nonsteroidal antiestrogens.
AB  - The preparation and characterization of some novel 2- and 3-substituted-7-methoxy
      4H-1-benzopyran-4-one are presented. The synthesized compounds were evaluated for
      their uterotrophic, antiuterotrophic and antiimplantation activities in mature
      female albino rats. 3-Benzyl-7-methoxy-4H-1-benzopyran-4-one (14) showed the
      highest uterotrophic activity (87%) based on dry uterine weight gain. The
      antifertility activity, as assessed by the post-coital antiimplantation activity
      test, was of weak potency for most compounds (14-29%). Among the products, the 2
      (4'-methoxyphenyl)-7-methoxy-4H-1-benzopyran-4-one (19) exhibited the highest
      antiestrogenic activity of 65%. It also elicited 31% of the uterotrophic activity
      of estradiol.

PMID- 11337104
TI  - Imidazo[1,2-a]quinoxalines: synthesis and cyclic nucleotide phosphodiesterase
      inhibitory activity.
AB  - A group of imidazo[1,2-a]quinoxalines have been synthesised from quinoxaline by
      condensation of an appropriate haloester or intramolecular cyclisation of a keto
      moiety on an intracyclic nitrogen atom. The reactivity of the heterocycle was
      explored through diverse reactions such as electrophilic substitution, lithiation
      and halogen-metal exchange to give access to a new series of derivatives.
      Confirmation of their structure was mainly performed by NMR, after careful
      assignment of the signals in comparison to previous attributions made on the
      parent imidazo[1,2-a]quinoxaline and discussion of available data in the
      literature. The cyclic nucleotide phosphodiesterase inhibitor activity of some of
      these derivatives has been assessed on isoenzymes type III and type lV. Compound
      15, 4-(methylamino)imidazo[1,2-a]quinoxaline-2-carbonitrile, exhibited potent
      relaxant activity on smooth muscle, with a potency similar to the one measured
      with SCA 40, its structural analogue in the imidazo[1,2-a]pyrazine series.

PMID- 11337105
TI  - Synthesis and structure-activity relationships of potential anticonvulsants based
      on 2-piperidinecarboxylic acid and related pharmacophores.
AB  - Using N-(2,6-dimethyl)phenyl-2-piperidinecarboxamide (1) and N-(alpha
      methylbenzyl)-2-piperidinecarboxamide (2) as structural leads, a variety of
      analogues were synthesised and evaluated for anticonvulsant activity in the MES
      test in mice. In the N-benzyl series, introduction of 3-Cl, 4-Cl, 3,4-Cl2, or 3
      CF3 groups on the aromatic ring led to an increase in MES activity. Replacement
      of the alpha-methyl group by either i-Pr or benzyl groups enhanced MES activity
      with no increase in neurotoxicity. Substitution on the piperidine ring nitrogen
      led to a decrease in MES activity and neurotoxicity, while reduction of the amide
      carbonyl led to a complete loss of activity. Movement of the carboxamide group to
      either the 3- or 4-positions of the piperidine ring decreased MES activity and
      neurotoxicity. Incorporation of the piperidine ring into a tetrahydroisoquinoline
      or diazahydrinone nucleus led to increased neurotoxicity. In the N-(2,6
      dimethyl)phenyl series, opening of the piperidine ring between the 1- and 6
      positions gave the active norleucine derivative 75 (ED50=5.8 mgkg(-1), TD50 =36.4
      mgkg(-1), PI=6.3). Replacement of the piperidine ring of 1 by cycloalkane
      (cyclohexane, cyclopentane, and cyclobutane) resulted in compounds with decreased
      MES activity and neurotoxicity, whereas replacement of the piperidine ring by a 4
      pyridyl group led to a retention of MES activity with a comparable PI.
      Simplification of the 2-piperidinecarboxamide nucleus of 1 into a
      glycinecarboxamide nucleus led to about a six-fold decrease in MES activity. The
      2,6-dimethylanilides were the most potent compounds in the MES test in each group
      of compounds evaluated, and compounds 50 and 75 should be useful leads in the
      development of agents for the treatment of tonic-clonic and partial seizures in
      man.

PMID- 11337106
TI  - Design, synthesis and binding properties of novel and selective 5-HT3 and 5-HT4
      receptor ligands.
AB  - This work reports the synthesis and the binding tests on the 5-HT3 and 5-HT4
      receptors of new thienopyrimidopiperazine and
      piperazinylacylaminodimethylthiophene derivatives, in order to identify potent
      and selective ligands for each receptor. The 3-amino-2-(4-benzyl-1-piperazinyl)
      5,6-dimethyl-thieno[2,3-d]pyrimidin-4(3H)-one derivative 28 showed the highest
      affinity and selectivity for the 5-HT3 over the 5-HT4 receptor (5-HT3 Ki=3.92 nM,
      5-HT4 not active), whereas the 2-[4-[4-(2-pyrimidinyl)-1
      piperazinyl]butanoylamino]-4,5-dimethyl-3-thiophenecarboxylic acid ethyl ester
      (41) showed the highest affinity and selectivity for the 5-HT4 over the 5-HT3
      receptor (5-HT4 Ki=81.3 nM, 5-HT3 not active). Conformational analyses were
      carried out on the compounds of the piperazinylacylaminodimethylthiophene series
      (39-42) taking compound 41 as the template.

PMID- 11337107
TI  - Initial induction and subsequent reduction of alpha(2u)-globulin in urine and
      serum of mature male rats after repeated intraperitoneal injections of
      (anti)estrogen.
AB  - The influence of sex (anti)hormones on expression of alpha(2u)-globulin (a2uG) is
      complex and has not been sufficiently detailed. In order to assess the
      specificity of sex (anti)hormone action on a2uG expression and the utility of
      this approach as a sensitive screening method, mature male rats were given daily
      intraperitoneal injections of 17beta-estradiol (E2), dihydrotestosterone (DHT),
      tamoxifen (TX) and flutamide (FL) for 5 consecutive days. They were employed as
      representatives of estrogen, androgen, antiestrogen and antiandrogen categories,
      respectively. Urinary a2uG was specifically altered with E2 (1 microg/kg/day) and
      TX (50 mg/kg/day), but not by DHT (1 mg/kg/day) or FL (50 mg/kg/day). E2 and TX
      temporarily increased urinary a2uG on days 1 or 2, and days 2-4, respectively,
      followed by a return to the control level, and then a decrease with E2. The
      reduction in urinary a2uG on day 6 was more pronounced than the drop in serum
      a2uG. Serum hormone levels, and liver and testis weights were not remarkably
      altered with any treatment. Another strong xenoestrogen, diethylstilbestrol, also
      significantly reduced urinary and serum a2uG at 1 mg/kg/day on day 6. However,
      the other xenoestrogens (100 mg/kg/day of bisphenol A, nonylphenol, and
      dichlorodiphenyltrichloroethane, and 10 mg/kg/day of dieldrin) and phytoestrogens
      (10 mg/kg/day of genistein and daidzein) were without any appreciable influence.
      The results indicate that urinary a2uG is a sensitive indicator of estrogen
      action in mature male rats, with two different responses, initial induction and
      subsequent reduction.

PMID- 11337108
TI  - Antioxidant effects of alpha tocopherol, ascorbic acid and L-methionine on lead
      induced oxidative stress to the liver, kidney and brain in rats.
AB  - Lead exposure related oxidative stress has been incriminated, at least in part,
      to its toxic effects in different organs. The present investigation was carried
      out to study the ameliorative effects of antioxidant (ascorbic acid, alpha
      tocopherol or L-methionine) alone and antioxidant (alpha tocopherol) plus a
      conventional chelator (CaNa2 EDTA) on some of the parameters indicative of
      oxidative stress in the liver, kidney and brain in lead-exposed rats. Rats were
      given 0 (n=6, healthy controls) or 1 mg of Pb(2+)/kg b.w (n=30) as lead acetate
      solution in sterile normal saline ip for a period of 4 weeks. The ip injections
      were then withdrawn and lead exposed rats were randomly divided into five equal
      groups. Six lead-exposed rats were given no treatment during the 5th week (Pb
      group) to serve as positive controls. The rest four groups received either
      ascorbic acid, alpha tocopherol or L-methionine in the 5th week at the daily dose
      of 100 mg/kg b.w orally or alpha tocopherol as above plus CaNa2 EDTA at the rate
      of 110 mg/kg b.w twice a day ip for a period of 4 days. All the animals were
      sacrificed 1 day after the end of the experiment, and the liver, kidney and brain
      were quickly excised for the estimation of lead burden and alteration in the
      oxidative indices. Lead exposure for a period of 4 weeks followed by a period of
      1 week to recover, resulted in significantly (P<0.05) higher accumulation of
      lead, associated with significant (P<0.05) increases in lipid peroxide level in
      the liver and brain, and non-protein bound thiol contents in the brain. Changes
      in the superoxide dismutase and catalase activities in lead-exposed rats did not
      reach statistical (P<0.05) significance. Treatment with antioxidants alone
      resulted in reversal of oxidative stress without significant decline in tissue
      lead burden. Tissue specific changes, following lead exposure and responses to
      the treatment with different antioxidants were recorded in the parameters of
      oxidative damage viz. lipid peroxide level, antioxidant enzymes and thiol
      contents.

PMID- 11337109
TI  - An evaluation of thiram toxicity on cultured human skin fibroblasts.
AB  - Thiram is widely used in agriculture as a fungicide and, to a lesser extent, as a
      vulcanizing agent in the rubber industry. In spite of the extensive use of
      thiram, knowledge on its toxicity and health risk remains limited, and few
      investigations have been performed to assess specific damage at the cellular and
      subcellular level. We report here the cytotoxic effects of thiram on cultured
      human skin fibroblasts. Our results demonstrated that thiram exposure induced a
      dose- and time-dependent decrease in the viable cell recovery with 100% cell
      death observed with a concentration of 5.0 mg/l. As judged by morphological
      changes and biochemical criteria, thiram-mediated cell death was not of the
      apoptotic but seemed to be of the necrotic type. This cell death was not
      associated with a modification of gene expression of different constituents of
      the extracellular matrix. A late increase of lactate production was evident after
      thiram treatment, suggesting a mitochondrial metabolic pathway dysfunction as
      reported by other authors using similar compounds. However, this phenomenon
      appeared as a secondary response to the toxic action of thiram. The cytotoxic
      effect of thiram is possibly due to an oxidant effect inherent to the structure
      of thiram and the interaction between thiram and vital cellular molecules.

PMID- 11337110
TI  - Dissection and weighing of accessory sex glands after formalin fixation, and a 5
      day assay using young mature rats are reliable and feasible in the Hershberger
      assay.
AB  - The rodent Hershberger assay has been used predominantly by the pharmaceutical
      industry to evaluate androgenic and antiandrogenic chemicals for potential
      therapeutic use. However, this assay has not yet been formally validated and
      standardized for use in toxicology testing. There are many variations in the
      protocol used for this assay. The weight of androgen-dependent tissues is a
      definitive endpoint in the Hershberger assay. To find out the reliable assay
      protocol with feasibility, although many possible factors may affect assay
      reliability, the present study consist of a series of three separate experiments
      focused on method of dissection and weighing of accessory sex glands (ASGs:
      ventral and dorso-lateral prostate, seminal vesicles together with coagulating
      glands, and Cowper's glands), animal age and number of doses. Furthermore, male
      pubertal assay, an alternative to the Hershberger assay, was also examined its
      reliability. Experiment 1 explored whether reliably accurate ASG weights can be
      obtained after formalin fixation. The ASGs were collected from castrated male
      rats (11 weeks of age) treated daily with corn oil, or testosterone propionate
      (TP, 0.25 mg/kg/day, s.c.) and p,p'-DDE (0 or 100 mg/kg/day, p.o.) for 5 days.
      One day after the final treatment, the ASGs were removed carefully and weighed
      separately, and then fixed overnight in a 10% neutral-buffered formalin and
      weighed again. After that, the tissues were dried overnight in an oven and
      weighed again. A high correlation between fresh and fixed tissue weights, and a
      high correlation between fixed and dried tissue weights were noted. The changes
      in the tissue weight due to fixation were marginal and were proportional to the
      fresh weights of the individual tissue. Standard deviation of the fixed tissue
      weight in each group and the magnitude of responses to TP or p,p'-DDE in fixed
      tissues were equivalent to those in fresh or dried tissues. These findings
      indicate that formalin fixation does not interfere with interpretation of assay
      results, and this procedure was used in the subsequent experiments. Experiments 2
      and 3 explored whether animal age or treatment duration altered assay
      sensitivity. In Experiment 2, antiandrogenic effect of p,p'-DDE (100 mg/kg/day)
      was detected after 5-and 10-day treatment irrespective of animal age (7 vs 11
      weeks). In Experiment 3, antiandrogenic effects of flutamide (1 and 10 mg/kg/day)
      and p,p'-DDE (10 and 100 mg/kg/day) were compared between two different
      protocols, the 10-day assay using peripubertal rats and the 5-day assay using
      young mature rats. Results demonstrated that both protocols could significantly
      detect antiandrogenic effects of flutamide and p,p'-DDE. These findings
      demonstrate that (1) dissection and weighing of ASGs after formalin fixation is
      reliable in the Hershberger assay, (2) when this procedure is used, the 5-day
      Hershberger assay using young mature rats, expected to be more feasible assay
      than the 10-day assay using peripubertal rats, is also reliable as well as the 10
      day assay using peripubertal rats. Furthermore, we confirmed that male pubertal
      assay with use of dissection and weighing of fixed tissues also reliable.

PMID- 11337111
TI  - Peripheral blood granulocyte activity following contact sensitization of rats
      with dinitrochlorobenzene.
AB  - Contact hypersensitivity (CHS) reaction is a classic example of a cell-mediated
      reaction. As the afferent phase of the reaction includes inflammation, CHS is a
      suitable model for investigating non-specific immunity. Some aspects of
      granulocyte activity in the afferent phase of experimentally induced CHS to
      dinitrochlorobenzene (DNCB) in two genetically different rat strains, AO and DA
      were examined in this study. A shift in the ratio of granulocytes to lymphocytes
      in favour of granulocytes and an increase in granulocyte survival were noted in
      DA rats. Granulocytes from both strains demonstrated increased levels of NBT
      reduction and an increase in their adhesion to plastic. Decreased granulocyte
      adhesion in the presence of monoclonal antibodies to beta2 integrins (anti
      CD11b/c and anti-CD18) points to the contribution of these molecules to
      granulocyte adhesiveness during the sensitization phase of CHS. Stimulation of
      adhesion in the presence of anti-CD11a antibody, points to a differential
      modulation of adhesion molecule activity during the afferent phase of CHS.
      Changes in functional activity of granulocytes demonstrated in this study might
      contribute to the development of CHS in rats.

PMID- 11337112
TI  - Chromium (VI) induces oxidative stress in the mouse brain.
AB  - Potassium dichromate was given to female Swiss mice (25 mg/kg per day) orally in
      water for 1-3 days. Brain homogenates were prepared to evaluate the occurrence of
      oxidative stress in this organ through the measurement of the antioxidant defense
      levels. and the extent of lipid peroxidation. In addition, mitochondrial
      fractions were isolated from brain homogenates to determine the production of
      reactive oxygen species in this subcellular fraction. The administration of
      potassium dichromate for 3 days caused increases of 72 and 74% in superoxide
      dismutase and catalase activities, respectively, in the homogenates. The
      treatment with this metal for 3 days increased brain homogenate chemiluminescence
      and thiobarbituric acid-reactive substances by 34 and 29%, respectively. The
      brain contents of the non-enzymatic antioxidants alpha-tocopherol and sulfhydryl
      groups decreased by 35 and 32%, respectively. Ascorbic acid levels were not
      modified by the administration of potassium dichromate. Finally, there was a
      significant increment in the mitochondrial production of oxidants in the brain of
      treated mice as compared with controls. These results suggest that chromium(VI)
      produces an increased formation of reactive oxygen species and brain lipid
      peroxidation. The increase in the antioxidant enzyme activities reflects an
      adaptive response against oxidative stress, while the reduction in the levels of
      non-enzymatic antioxidants might be due to their reaction with reactive oxygen
      species generated during the metabolism of chromium(VI).

PMID- 11337122
TI  - Risk factors to tick infestations and their occurrence on horses in the state of
      Sao Paulo, Brazil.
AB  - From December 1998 to March 1999, 40 stud farms were studied in the state of Sao
      Paulo, Brazil. During visits to farms, horses reared under grazing conditions
      were examined for the presence of ticks. On each farm visit, horse pastures were
      closely inspected and a questionnaire was given to the farm supervisor with the
      purpose of gaining information about ecological and management variables
      (independent variables) that could be associated with the presence and
      infestation levels of ticks on the farm (dependent variables). Three tick species
      were found during the study. Anocentor nitens, Amblyomma cajennense and Boophilus
      microplus were present on horses from 38 (95%), 20 (50%) and four (10%) farms,
      respectively. All farms that had A. cajennense or B. microplus infestations also
      had A. nitens infestations. Only one of the four farms with B. microplus
      infestations on the horses also had A. cajennense infestations. Two farms had all
      horses free of ticks. There was a strong association between the presence of
      infestation by B. microplus on horses and the simultaneous use of a grazing area
      by cattle and horses (P = 0.000). There was no statistical association between
      any of the independent variables and the presence or infestation level of A.
      nitens on the horses (P > 0.20). The presence of A. cajennense was statistically
      associated with the presence of at least one mixed overgrowth pasture in the farm
      (P = 0.001). A mixed overgrowth pasture means the presence of undesired plants
      such as bushes and shrubs in the pasture. The presence of high levels of A.
      cajennense on horses was also associated with the presence of at least one mixed
      overgrowth pasture in the farm (P = 0.026). The regular use of acaricides was
      statistically associated with the presence of ticks on the horses (P < 0.05),
      making this procedure a result of the inefficacy of controlling ticks on the
      farms. The occurrence of human infestation by ticks was statistically associated
      with the presence of A. cajennense on the horses (P=0.000). The presence of at
      least one mixed overgrowth pasture on the farm was associated (P = 0.000) to
      either higher horse densities and to farms that did not mow all the pastures once
      a year, indicating that mowing all the pastures at least once a year can be
      considered a protective factor against the presence of mixed overgrowth pastures
      on the farm, and consequently, against the presence of A. cajennense on the
      horses.

PMID- 11337123
TI  - Long term improvement in the treatment of canine leishmaniosis using an antimony
      liposomal formulation.
AB  - Pharmacokinetic and clinical effectiveness of liposome-encapsulated N
      methylglucamine antimoniate (LMA) was performed in dogs suffering from
      experimental leishmaniosis. LMA was compared with N-methylglucamine antimoniate
      (MGA), the same drug in its free form. Sb plasma concentrations for LMA were
      always higher than those for MGA. Mean residence time (MRT), half-life time
      (t(1/2)) and clearance (Cl) showed that Sb was eliminated slower after liposome
      administration. The high volume of distribution (Vd) obtained with LMA suggests
      that Sb could achieve therapeutic concentrations in parasite-infected tissues.
      Average plasma concentration at steady state (Css(ave)) shows that Sb body
      concentrations after LMA treatment (9.8 mg/kg Sb, each 24h) would be effective in
      Leishmania infantum canine infection. Comparing LMA with MGA in a 1-year follow
      up we observed no relapses for LMA and total protein and gammaglobulin
      concentrations were within normal range, while for MGA both began to rise 3
      months after treatment. Use of antimonial liposomal formulations may restore
      effectiveness to an existing drug and reduce toxicity.

PMID- 11337124
TI  - A comparative evaluation of parasitological tests and a PCR for Trypanosoma
      evansi diagnosis in experimentally infected water buffaloes.
AB  - In this study five parasitological methods and a polymerase chain reaction (PCR)
      were compared for the diagnostic sensitivity for Trypanosoma evansi in
      experimentally infected water buffaloes over a period of 15 weeks. The combined
      estimates of sensitivity (CE(se)) of the PCR proved to be highest at 78.2%,
      closely followed by the mouse inoculation (MI), the micro-haematocrite
      centrifugation technique (MHCT) and the mini-anion-exchange centrifugation
      technique (MAECT) with CE(se) of, respectively, 74.0, 69.6 and 62.4%. The CE(se)
      of the buffy-coat technique (BCT) at 38.6% and the sodium dodecyl sulfate (SDS)
      clarification technique at 25.1% were considerably lower. PCR detected
      consistently all buffaloes infected from week 3 post-infection (PI) onwards. For
      MI this occurred after 5 weeks PI while for MHCT and MAECT these sustainable high
      levels were reached in the 7th week PI. BCT and SDS never detected all buffaloes
      infected. The influence of time and temperature on the viability of T. evansi in
      heparinized blood from water buffalo was also studied. In general we observed
      that the survival time tends to be longer when blood is kept at 4 degrees C. In
      samples kept in direct sunlight parasites became undetectable with the MHCT after
      30min. After treatment of the water buffaloes with diminazene aceturate, the PCR
      signal disappeared within 24h.

PMID- 11337125
TI  - Vaccination of sheep against Fasciola hepatica with homologous fatty acid binding
      proteins.
AB  - The current study was designed to test the immunoprophylactic properties of
      native (nFh12) and recombinant (rFh15) antigens from Fasciola hepatica in sheep
      subsequently infected with the fluke. Thirty lambs were divided into six groups
      according to various patterns of immunisation and times of infection and
      necropsy. The antigens were emulsified in Freund's adjuvant. Levels of specific
      anti-nFh12 and anti-rFh15 antibodies rose rapidly by 2 weeks after the first
      immunisation and were always significantly higher in immunised-infected sheep
      than in control-infected sheep. On completion of the trial there was no
      difference in fluke burden between groups vaccinated with either of the antigens
      and non-immunised controls. However, worm size and faecal egg counts were
      significantly diminished in the sheep vaccinated with either of the antigens,
      suggesting an anti-fecundity effect. This is the first report of experimental
      vaccination of sheep against F. hepatica with purified native and recombinant
      antigens related to fatty acid binding proteins.

PMID- 11337126
TI  - Evaluation of cercarial antigen for the serodiagnosis of fasciolosis in
      experimentally and naturally infected sheep.
AB  - The value of cercarial antigen for diagnosis of experimental and natural sheep
      fasciolosis was studied by enzyme linked immunosorbent assay (ELISA) and enzyme
      linked immunotransfer blot (EITB). In ELISA, the antibody levels of
      experimentally infected sheep with Fasciola gigantica appeared at 2 weeks post
      infection (PI), gradually increased till 7 weeks PI and nearly remained at the
      same level from 7 to 13 weeks PI (the end of experiment). Also, the sensitivity
      and specificity of cercarial antigen for diagnosis of naturally sheep fasciolosis
      were 100 and 90%, respectively. In EITB, in the sheep experimentally infected
      with F. gigantica, the band of 32.5kDa molecular weight polypeptide appeared at 2
      weeks PI and continued till the end of experiment. Also, the cercarial antigen
      recognized 32.5kDa molecular weight band with all sera from naturally infected
      sheep with fasciolosis (n = 25). This band did not cross-react when tested with
      sera from infected sheep with Cysticercus tenuicollus (n = 20). This study
      suggests that, the 32.5kDa molecular weight polypeptide could be used as
      sensitive and specific epitope for the serodiagnosis of sheep fasciolosis.

PMID- 11337127
TI  - An enzyme-linked immunosorbent assay (ELISA) for detection of antibodies against
      Toxocara vitulorum in water buffaloes.
AB  - Toxocara vitulorum, a parasite of the small intestine of cattle and water
      buffaloes, is mainly acquired by calves via the colostrum/milk from infected
      cows. To understand the development of immune responses in calves, antibody
      levels to a soluble extract antigen (Ex) from T. vitulorum infective larvae were
      measured by an indirect ELISA with sera of 15 buffalo calves, which were sampled
      every 15 days for the first 180 days after birth and 9 buffalo cows during the
      perinatal period. From all serum samples examined during the first 180 days,
      antibody level was lowest and highest in calves at 1 day of age before and after
      suckling colostrum, respectively, suggesting that the origin of antibodies was
      the colostrum. Immediately after birth, antibody levels in suckled calves
      remained at high levels until day 15, began to decrease to lower levels between
      15 and 30 days and remained relatively stable until 120 days. By comparing the
      immune responses of these animals with their parasitological status it was
      considered possible to determine if passively acquired or actively produced
      antibodies provided protection against the infection. High numbers of T.
      vitulorum eggs in the feces between 30 and 60 days indicated that passively
      acquired antibodies did not provide protection against the infection, at least
      during these first days, and the maximum fecal egg counts during 30-45 days were
      coincident with decreased antibody levels. Between 60 and 120 days, when serum
      antibodies were detected at reduced, but stable levels, adult nematodes were
      expelled from the intestines and no more T. vitulorum eggs were found, suggesting
      development of acquired resistance. However, the potential and functional
      protective role of the antibodies against T. vitulorum infection and the process
      of self-cure requires further investigation.

PMID- 11337128
TI  - Molecular phylogeny and biogeography of North American isolates of Anaplasma
      marginale (Rickettsiaceae: Ehrlichieae).
AB  - Anaplasma marginale (A. marginale) is a tick-borne ehrlichial pathogen of cattle
      that causes the disease anaplasmosis. Six major surface proteins (MSPs) have been
      identified on A. marginale from cattle and ticks of which three, MSP1a, MSP4 and
      MSP5, are from single genes and do not vary within isolates. The other three,
      MSP1b, MSP2 and MSP3, are from multigene families and may vary antigenically in
      persistently infected cattle. Several geographic isolates have been identified in
      the United States which differ in morphology, protein sequence and antigenic
      properties. An identifying characteristic of A. marginale isolates is the
      molecular weight of MSP1a which varies in size among isolates due to different
      numbers of tandemly repeated 28-29 amino acid peptides. For these studies, genes
      coding for A. marginale MSP1a and MSP4, msp1alpha and msp4, respectively, from
      nine North American isolates were sequenced for phylogenetic analysis. The
      phylogenetic analysis strongly supports the existence of a south-eastern clade of
      A. marginale comprised of Virginia and Florida isolates. Analysis of 16S rDNA
      fragment sequences from the A. marginale tick vector, Dermacentor variabilis,
      from various areas of the United States was used to evaluate possible vector
      parasite co-evolution. Our phylogenetic analysis supports identity between the
      most parsimonious tree from the A. marginale MSP gene data and the tree that
      reflected the western and eastern clades of D. variabilis. These phylogenetic
      analyses provide information that may be important to consider when developing
      control strategies for anaplasmosis in the United States.

PMID- 11337129
TI  - Effectiveness of a synthetic lure to reduce blowfly strike incidence: preliminary
      observations.
AB  - The effectiveness of a synthetic lure system (Lucitrap) to reduce blowfly strike
      incidence was assessed in a field trial conducted on two properties located in
      southern Queensland, Australia. Nine hundred and fifty sheep were randomised to
      treatment (one or more Lucitrap per 100 sheep) and control paddocks. Sheep were
      physically inspected for flystrike each month between August 1999 and May 2000.
      On one property, the risk of flystrike in the control group was 1.86 times (95%
      confidence interval, 1.19-2.90) greater than that in the treatment group. On the
      other property, two cases of flystrike were detected in the control group, but no
      cases were detected in the treatment group. These preliminary observations
      suggest that the use of Lucitrap can reduce the incidence of blowfly strike by up
      to about one-half. Blowfly traps have a role in controlling flystrike in
      circumstances in which sheep are susceptible to flystrike and the likelihood of
      flystrike occurring is at least moderate. The use of fly traps could assist the
      Australian wool industry to meet targets of reduced pesticide use.

PMID- 11337130
TI  - Chronic stress differentially regulates glucocorticoid negative feedback response
      in rats.
AB  - Exposure to chronic stress is thought to play an important role in the etiology
      of depression. In this disorder, a disrupted negative feedback response to
      exogenous glucocorticoids on cortisol secretion has been indicated. However, the
      regulation of glucocorticoid negative feedback by chronic stress is not fully
      understood. In the present study, we investigated the effects of chronic stress
      administered by water immersion and restraint (2 h/day) for four weeks on the
      glucocorticoid feedback in rats. In the acutely (one-time) stressed rats, the
      basal plasma corticosterone (CORT) level was markedly elevated, remained at high
      levels for 5 h after the termination of stress, and then decreased. In the
      chronically stressed rats, the CORT level was initially elevated similarly, but
      rapidly decreased at 2 h. In the dexamethasone (DEX) suppression test, the peak
      CORT level in response to stress was not suppressed by DEX in the acutely
      stressed rats, but was significantly suppressed in the chronically stressed rats.
      In contrast, the suppressive effects of DEX on the basal CORT secretion in naive
      rats were attenuated in the chronically stressed rats. In the chronically
      stressed hippocampus, which plays an important role in the regulation of the
      glucocorticoid feedback response, the binding of [3H]DEX was decreased and the
      increased response of activator protein-1 induced by acute stress was abolished.
      These results suggest that chronic stress induces a hypersuppressive state for
      induced CORT secretion in response to acute stress, which is caused by partial
      habituation, coping, and adaptation to the stressor, whereas it induces a
      hyposuppressive state for the basal CORT secretion, which is caused by
      glucocorticoid receptor downregulation. These mechanisms may be involved in the
      stress-induced neural abnormalities observed in depression.

PMID- 11337131
TI  - Feeding demand conditions and plasma cortisol in socially-housed squirrel monkey
      mother-infant dyads.
AB  - Previous studies have demonstrated that experimentally altering the accessibility
      and availability of food can have profound impact on behavior and adrenocortical
      activity in nonhuman primate species. In this study, groups of mother-infant
      squirrel monkey dyads were housed in either high demand (HFD: 120% normal daily
      food intake provided), low demand (LFD: 600% normal daily food intake provided)
      or variable demand (VFD: alternating two-week blocks of low demand and high
      demand) conditions for 12 weeks. During the 12-week experimental foraging phase,
      animals in the HFD group exhibited prolonged and consistent cortisol elevations.
      The cortisol levels in the VFD group reflected the ambient demand condition, with
      higher levels exhibited during the high demand phases of the study, and lower
      values when the low demand condition was in effect. Overall, mothers were more
      affected by the experimental manipulation than were infants. The experimental
      condition did not affect the infants' response to a 24-h separation from their
      mothers. A suppression of cortisol levels, particularly in the HFD group, was
      observed upon resumption of ad-libitum feeding.

PMID- 11337132
TI  - Antidepressant-like actions of pregnancy, and progesterone in Wistar rats forced
      to swim.
AB  - In rats, some behavioral changes occurring during pregnancy related to the
      presence of progesterone may be analyzed in the forced swimming task (FST), which
      is designed to test the antidepressant profile of drugs. The present study was
      aimed to analyze in pregnant rats, in rats after delivery, or in rats after
      receiving progesterone those behavioral changes displayed in the FST. We
      hypothesize that pregnancy and progesterone will produce antidepressant-like
      effects in rats forced to swim. Therefore, pregnant rats (14th, 17th, and 20th
      days), or rats after delivery (3rd, and 7th days) were tested in the FST.
      Ovariectomized rats receiving saline (0.9%; i.p.), clomipramine (1.25 mg/kg;
      i.p.), or desipramine (2.14 mg/kg; i.p.) for 28 days were also tested in the FST.
      In a second series of experiments, ovariectomized rats receiving vehicle or
      progesterone (0.5 mg/kg; or 2.0 mg/kg; sc.) were tested in the FST. Locomotion
      was evaluated in the open field test. Results showed that in the FST: 1)
      pregnancy (P < 0.05), or progesterone (P < 0.05), or desipramine (P < 0.05),
      reduced immobility by increasing climbing; 2) clomipramine (P < 0.05) reduced
      immobility by increasing swimming; 3) rats tested after delivery displayed
      similar behavior than control rats. A lower locomotion was observed only at the
      end of pregnancy. In conclusion, results suggest that during pregnancy, a
      reproductive process characterized by its high levels of progesterone,
      antidepressant-like effects can be found.

PMID- 11337133
TI  - Prolactin response to d-fenfluramine in postmenopausal women on and off ERT:
      comparison with young women.
AB  - Estrogen is thought to have an impact on both psychological well being and
      cognitive function. The biological basis to this is not fully understood, but may
      involve estrogen's interactions with central serotonergic (5-HT) systems.
      Therefore, we studied the effect of long-term estrogen hormone replacement
      therapy (ERT) on central 5-HT tone in healthy postmenopausal women and made
      comparisons with young women. Prolactin (PRL) responses to the specific 5-HT
      releasing and re-uptake inhibiting agent, d-fenfluramine, were measured in three
      groups of healthy women: 11 young, 11 postmenopausal on long-term ERT, and 11
      postmenopausal ERT naive. PRL responses were significantly decreased in ERT naive
      women compared to young healthy women. In contrast, PRL responses were not
      different between estrogen-treated and young women. Overall, there was a
      significant relationship between older age and lower PRL responsivity. These
      results suggest that central 5-HT tone is reduced in healthy postmenopausal women
      who are ERT naive, but not in postmenopausal women who have received prolonged
      estrogen treatment. Estrogen may modulate age-related changes in 5-HT tone. This
      may partly explain why estrogen can decrease vulnerability to mood disorders and
      cognitive changes in postmenopausal women.

PMID- 11337134
TI  - Social stress during pregnancy and lactation affects in guinea pigs the male
      offsprings' endocrine status and infantilizes their behaviour.
AB  - This study investigated the influence of the social environment during pregnancy
      and lactation on the male offsprings' endocrine parameters and behaviour in
      guinea pigs. The subjects studied were sons whose mothers had either lived in a
      stable social environment during pregnancy and lactation or in an unstable social
      environment during this period of life. The stable social environment was made by
      keeping the group composition (one male, five females) constant; in the unstable
      social environment situation every third day, two females from different groups
      were exchanged. After weaning, seven groups of sons, whose mothers had lived in
      an unstable social environment and seven groups of sons, whose mothers had lived
      in a stable social environment, consisting of two males each, were established.
      From their 20th through their 100th day of age the spontaneous behaviour of the
      males was recorded in their home cages. On the endocrine level, cortisol- and
      testosterone-concentrations in serum as well as adrenal tyrosine hydroxylase
      activities were determined. Sons, whose mothers had lived in an unstable social
      environment, showed significantly higher amounts of resting with bodily contact
      than sons, whose mothers had lived in a stable social environment. Additionally,
      they displayed this behaviour to an older age than the latter sons. Further on,
      sons, whose mothers had lived in an unstable social environment, displayed
      significantly higher frequencies of courtship behaviour than sons, whose mothers
      had lived in a stable social environment, which was integrated into play
      behaviour. These behavioural data point to an infantilization of sons, whose
      mothers had lived in an unstable social environment. The behavioural patterns
      corresponded with a delayed development of the hypothalamo-pituitary
      adrenocortical-axis and a lower activity of the sympathetic-adrenomedullary
      system compared to sons whose mothers had lived in a stable social environment.
      Testosterone did not differ between both categories of males. Thus, the
      instability of the social environment during pregnancy and lactation had distinct
      and not yet described effects on the behaviour and endocrine system of the male
      offspring.

PMID- 11337135
TI  - Lack of effect of HPA axis hyperactivity on hormonal responses to d-fenfluramine
      in major depressed patients: implications for pathogenesis of suicidal behaviour.
AB  - There is evidence for inhibitory effects of adrenocorticosteroids on serotonergic
      (5-HT) activity. However, in depression the relationship between altered cortisol
      levels and brain 5-HT function remains to be clarified. The aim of this study was
      to investigate whether hypothalamic-pituitary-adrenal (HPA) axis hyperactivity is
      associated with 5-HT dysfunction in depressed patients, especially in those with
      suicidal behaviour. Cortisol levels following the dexamethasone suppression test
      (DST, 1 mg PO) and prolactin, corticotropin and cortisol responses to the d
      fenfluramine test (d-FEN, 45 mg PO) - a specific 5-HT releaser/uptake inhibitor -
      were measured in 71 drug-free DSM-IV major depressed inpatients (40 with a
      history of suicide attempt, 31 without) and 34 hospitalized healthy control
      subjects. Depressed patients showed higher post-DST cortisol levels but similar
      responses to d-FEN compared with control subjects. Hormonal responses to d-FEN
      were not correlated with cortisol levels (basal or post-DST). Among the depressed
      patients, DST suppressors and DST nonsuppressors exhibited no significant
      difference in endocrine responses to d-FEN. However, patients with a history of
      suicide attempt, when compared with patients without such a history, showed lower
      hormonal responses to d-FEN but comparable basal and post-DST cortisol levels.
      Taken together these results suggest that, in depression, HPA axis hyperactivity
      is not responsible for the reduced 5-HT activity found in patients with a history
      of suicidal behavior.

PMID- 11337136
TI  - Rapid pathotyping of Newcastle disease virus (NDV) using fluorogenic probes in a
      PCR assay.
AB  - Hybridisation of PCR fragments with fluorogenic probes specific for pathotype
      allowed an estimation of pathogenicity of Newcastle disease virus (NDV) isolates
      using a modified TaqMan procedure. Six probes were used, designed to recognise
      nucleotide sequences in the fusion protein gene sequence corresponding to the
      precursor protein F0 cleavage site of both virulent and avirulent viruses. Forty
      three of the 45 isolates tested, including 18 examined in a blind study were
      pathotyped successfully and rapidly, with close correlation between cleavage site
      nucleotide sequences, TaqMan results and intracerebral pathogenicity index (ICPI)
      values. One isolate, which could not be pathotyped by nucleotide sequencing, was
      shown using the TaqMan system to be a mixture of virulent and avirulent NDV. The
      results of this study suggest that using this modified TaqMan protocol, the
      likely virulence of most ND isolates can be determined rapidly and reproducibly.

PMID- 11337137
TI  - A guinea pig model of low-dose Mycobacterium bovis aerogenic infection.
AB  - In order to develop a model of Mycobacterium bovis infection with pathogenetical
      relevance, a modified version of the Henderson apparatus was used to deliver
      infectious aerosols directly to the snouts of guinea pigs. Aerosols generated
      from 10(6), 10(7), 10(8)CFU/ml M. bovis suspensions established disease in every
      animal, with estimated retained doses of 10, 100, 1000 CFU, respectively. For
      comparison, other guinea pigs were inoculated with 100 CFU M. bovis
      intramuscularly (i.m.). Pathology and bacterial colonisation of lungs and spleen
      varied according to the dose and route of inoculation. Animals inoculated i.m.
      gave a significant cutaneous tuberculin hypersensitivity reaction earlier after
      testing than those infected aerogenically. A serological response to M. bovis
      antigens was detected in all infected animals. Intensity of antigen recognition
      was dose-dependent and although the range of antigens recognised varied between
      animals, a 25 kDa antigen present in the cell fraction was serodominant. Thus, a
      reproducible guinea pig model has been defined that may be suitable for
      virulence, vaccination, and immunological studies.

PMID- 11337138
TI  - Escherichia coli strains from edema disease: O serogroups, and genes for Shiga
      toxin, enterotoxins, and F18 fimbriae.
AB  - The objectives of the research were to determine the presence of the gene
      sequences for Shiga Toxin 2e (Stx2e), enterotoxins (ST-I, ST-II and LT-I), and
      F18 fimbriae in 144 Escherichia coli strains isolated from pigs with edema
      disease; to assess the ability of stx2e(+) strains to produce Stx2e; and to
      determine the O serogroups of the E. coli strains. Presence of the genes was
      determined by polymerase chain reaction (PCR), production of Stx2e was assessed
      by cytotoxicity for Vero and Hela cells, O serogroups were identified by
      agglutination with specific antisera. Of the 144 strains tested, 99 were stx2e(+)
      by PCR, but only 45 of these were Stx2e(+) in the cell culture assays. Among the
      99 stx2e(+) strains, PCR detected the genes for F18ab, ST-I, ST-II, LT-I in 76,
      40, 31 and 16 strains, respectively. Forty-one of the 99 sxt2e(+) strains
      belonged to O group 139; the rest did not belong to the classical edema disease O
      serogroups. It is likely that the enterotoxins, whose genes were detected at high
      frequency, are responsible for diarrhea seem in pigs with edema disease in
      Brazil.

PMID- 11337139
TI  - The SEF14 fimbrial antigen of Salmonella enterica serovar Enteritidis is encoded
      within a pathogenicity islet.
AB  - The DNA sequence of the chromosomal gene cluster encoding the SEF14 fimbriae of
      Salmonella enterica serovar Enteritidis was determined. Five contiguous open
      reading frames, sefABCDE, were identified. The sefE gene shared significant
      homology with araC-like positive regulators. Serovar-associated virulence plasmid
      (SAP) genes orf7,8,9 and pefI were identified immediately adjacent to the sef
      operon. The pefI gene encoded a putative regulator of the Plasmid-encoded
      fimbrial antigen (PEF) expression. The entire sef--pef region, flanked by two IS
      like elements, was inserted adjacent to leuX that encoded a transfer RNA
      molecule. The organisation of this region was suggestive of a classic
      pathogenicity islet. Southern hybridisation confirmed two copies of the SAP
      derived orf7,8,9 and pefI region in S. Enteritidis, one in the chromosome and one
      on the SAP. Of other group D Salmonella, only S. Blegdam and S. Moscow harboured
      both chromosomal and plasmid copies of pefI--orf9 region although polymorphism
      was evident.

PMID- 11337140
TI  - Induction of cross-protection in mice against dolphin Erysipelothrix
      rhusiopathiae isolates with a swine commercial vaccine.
AB  - Erysipelothrix rhusiopathiae is well known to cause disease in dolphins. This
      disease occurs either in an peracute way, leading to mortality even before
      clinical signs are observed or in a sub-acute way, characterized by rhomboidal
      skin lesions, that can be treated with penicillin or its derivatives. Commercial
      swine vaccines, containing inactivated serotype 2 strains, are currently used for
      vaccination but it is not known whether these vaccines induce protection against
      E. rhusiopathiae isolates from dolphins. In the present study, it was
      demonstrated in a mouse model that vaccination with a commercial swine vaccine
      (Eurovac Ery, Eurovet, Belgium) containing inactivated serotype 2 E.
      rhusiopathiae strains induced protection against challenge with three E.
      rhusiopathiae isolates from dolphins. The duration of the protection varied,
      depending on the challenging isolate, between 8 and >23 weeks. There was however
      no positive correlation between the amount of antibodies at the moment of
      challenge and the observed protection. In conclusion, vaccination trials in mice
      indicate that commercial serotype 2 swine Erysipelothrix vaccines induce
      protection against erysipelas caused by dolphin pathogenic isolates.

PMID- 11337141
TI  - The major bovine mastitis pathogens have different cell tropisms in cultures of
      bovine mammary gland cells.
AB  - We previously showed that Staphylococcus aureus cells adhered mainly to an
      elongated cell type, present in cultures of bovine mammary gland cells. Moreover,
      we showed that this adhesion was mediated by binding to fibronectin. The same in
      vitro model was used here, to study adhesion of other important mastitis
      pathogens. Like the S. aureus strains, the Streptococcus dysgalactiae strains
      adhered mainly to elongated cells, which seemed to be mediated by fibronectin
      binding. In contrast, Streptococcus uberis strains adhered mainly to cubic cells.
      Since the cubic cells did not express fibronectin and S. uberis cells bound
      fibronectin less efficiently, the adhesion of S. uberis cells was independent of
      fibronectin binding. Streptococcus agalactiae strains adhered poorly to both cell
      types. The specificity and efficiency of adhesion of Escherichia coli strains was
      strongly strain dependent. None of the S. agalactiae and E. coli strains tested
      was able to bind fibronectin efficiently. The results suggest that the different
      mastitis pathogens have different target cell specificities and use different
      mechanisms to adhere to cells of the bovine mammary gland.

PMID- 11337142
TI  - Monitoring of transmission of Salmonella enterica serovars in pigs using
      bacteriological and serological detection methods.
AB  - The standard method to detect Salmonella positive pigs is bacteriological
      examination of the faeces, but in recent years the use of Salmonella-ELISA's have
      become available to screen pigs for serological evidence of infection. This study
      was conducted to monitor the transmission of five different Salmonella enterica
      serovars (S. Typhimurium, S. Brandenburg, S. Panama, S. Livingstone, and S.
      Goldcoast) in fattening pigs and to test the feasibility of Salmonella-ELISA,
      using seeder pigs as a mode of transmission. Serovar dependence in transmission
      was observed. The Salmonella-ELISA proved to be useful to detect S. Typhimurium
      and S. Brandenburg in herds but was of limited value to demonstrate S.
      Livingstone, S. Goldcoast, and S. Panama.

PMID- 11337143
TI  - Serological study of the frequency of leptospiral infections among dairy cows in
      farms with suboptimal reproductive efficiency in Galicia, Spain.
AB  - Between March 1996 and September 1997, 15 farms located in Galicia (NW Spain) and
      experiencing suboptimal reproductive efficiency were visited and blood samples
      were obtained from all the lactating cows (n=442). Additionally, 1060 samples
      were obtained monthly from a cohort of 219 lactating cows belonging to nine of
      the farms between March 1996 and April 1997. All the samples were tested by
      microscopic agglutination (MAT) using live antigens representing the following
      Leptospira interrogans serogroups: Australis, Autumnalis, Ballum, Canicola,
      Grippotyphosa, Icterohaemorrhagiae, Louisiana, Pomona, Sejroe, Shermani and
      Tarassovi. Eighty-one of the 442 cows were positive against one or more
      serogroups (P=18.33%). Serologically, L. bratislava and L. grippotyphosa were
      detected as the most prevalent serovars (P=7.92 and 7.69%, respectively) and as
      the serovars against which the probability of seroconversion was highest (P=0.27
      and 0.25, for a 12-month period, respectively) among those studied. The
      proportional hazards regression method was used for evaluating the seasonal trend
      of seroconversions against these two serovars. The risk of seroconversion against
      L. grippotyphosa was significantly higher during spring. The risk of
      seroconversion against L. bratislava did not differ significantly among seasons.
      Our results suggest that infections by L. bratislava did not follow, among the
      study animals and during the study period, the pattern typically described for
      non-adapted serovars, pointing out the possibility that some strains of this
      serovar could behave as adapted serovars.

PMID- 11337144
TI  - Studies about the mechanism of internalization by mammary epithelial cells of
      Escherichia coli isolated from persistent bovine mastitis.
AB  - The purpose of this study was to investigate the interaction between Escherichia
      coli and primary mammary epithelial cell cultures derived from cows with
      persistent intramammary infection (IMI). Two strains of E. coli, isolated from
      the milk of two different cows suffering from persistent E. coli IMI were tested
      for adhesion to and invasion of three primary mammary epithelial cell cultures
      derived from mammary biopsies of the two infected cows. Intracellular E. coli
      were detected during five days post infection in vitro. Both strains of E. coli
      adhered to and invaded monolayers of all three primary mammary epithelial cell
      cultures. One strain adhered less but invaded more than the other. Comparison
      with other mammary pathogens indicated that E. coli invaded the cells less
      efficiently than Staphylococcus aureus, about as efficiently as Streptococcus
      dysgalactiae and more efficiently than Streptococcus uberis. The mechanism of E.
      coli invasion was studied using the cytoskeleton disrupting agents colchicine and
      cytochalasin D. These compounds inhibited the invasion of E. coli. Invasion of E.
      coli could also be inhibited by the phosphokinase inhibitors genistein and
      staurosporin in a dose-dependent fashion. Phorbol-myristyl-acetate (PMA) had no
      effect on the invasion of E. coli. Histology of mammary tissue revealed chronic
      inflammatory changes in quarters that were persistently infected by E. coli.
      Intracellular bacteria were not detected in mammary tissue sections. Polymerase
      chain reaction (PCR) analysis suggested that the two strains of E. coli lacked
      genes encoding for bundle-forming pili (bfpA), intimin (eae) and translocated
      intimin receptor (tir), which are characteristic for enteropathogenic E. coli
      (EPEC).

PMID- 11337145
TI  - Microencapsulation of ibuprofen and Eudragit RS 100 by the emulsion solvent
      diffusion technique.
AB  - The emulsion solvent diffusion was employed to prepare modified release
      microspheres of ibuprofen. The technique was optimised for the following
      processing variables: the absence/presence of baffles in the reaction vessel,
      agitation rate and drying time. Thereafter, the influence of various formulation
      factors on the microencapsulation efficiency, in vitro drug release and
      micromeritic properties was examined. The variables included the methacrylic
      polymer, Eudragit(R) RS 100, ibuprofen content and the volume of ethanol used
      during microencapsulation. The results obtained were then interpreted on a
      triangular phase diagram to map the region of microencapsulation, as well as
      those formulations that yielded suitable modified release ibuprofen microspheres.

PMID- 11337146
TI  - Acrylic microspheres for oral controlled release of the biguanide buformin.
AB  - Spherical microparticles based on methacrylic acid-methyl methacrylate copolymer
      have been developed. The method chosen for the preparation of such microparticles
      was suspension radical copolymerization of acrylic comonomers in the presence of
      the ethyleneglycol dimethacrylate as crosslinking agent. The microparticles
      obtained were characterised by inverse size exclusion chromatography, scanning
      electron microscopy, swelling degree and exchange capacity. The porous volume of
      the microspheres ranged from 0.086 ml/g for the microparticles produced by a
      methacrylic acid/methyl methacrylate ratio of 1/3 and a 10% degree of
      crosslinking, to 8.57 ml/g for the microparticles produced by a methacrylic
      acid/methyl methacrylate ratio of 3/1 and 2% degree of crosslinking (in 0.1 N
      NaCl in phosphate buffer pH 7.4). Also the pore diameter of the swollen
      microparticles ranged from a few to 120 A. Buformin tosylate - a classical
      hypoglycaemic drug - was included in the polymer network of the microparticles
      during the polymerization process. Due to the water solubility of the drug and
      its low solubility in the organic phase, the entrapment yield did not exceed 15%.
      However the amount of encapsulated drug as well as the drug released from the
      microparticles, was dependent on the methacrylic acid/methyl methacrylate ratio,
      the degree of crosslinking and solvent/comonomers ratio.

PMID- 11337147
TI  - Preparation, characterisation and photosensitivity studies of solid dispersions
      of diflunisal and Eudragit RS100 and RL100.
AB  - Solid dispersions of diflunisal (DIF) with Eudragit RS100 (RS) and RL100 (RL)
      with different drug-to-polymer ratios were prepared by a solvent method
      (coevaporates) and were characterised in the solid state in comparison with the
      corresponding physical mixtures. The work was aimed at characterising the
      interactions occurring between DIF and RS or RL polymers, along with their
      influence on the in-vitro drug-dissolution pattern. The findings suggest that the
      drug did not change its crystalline form within the polymer network. Drug
      dispersion in the polymer matrix strongly influences its dissolution rate, which
      appears slower and more gradual while increasing the polymer ratios. Moreover,
      DIF is known to be a photosensitive compound, and its photoproduct has been found
      to be a toxic agent. This can be evidenced by testing red blood cell membranes
      for their resistance to the osmotic shock induced by UVA irradiation in the
      presence of DIF. The presence of some DIF/RS coevaporates was shown to reduce
      significantly the drug photosensitization process towards cell membranes. This
      suggests the possibility of combining the design of a drug delivery system with a
      photoprotective strategy.

PMID- 11337148
TI  - Stabilization of eptifibatide by cosolvents.
AB  - Eptifibatide is a potent and highly specific inhibitor of platelet receptor
      glycoprotein IIb/IIIa and is indicated in the treatment of acute coronary
      syndrome. The commercial product Integrilin(R) (eptifibatide) Injection requires
      a cold/refrigerator storage condition. In an effort to improve the drug stability
      for room temperature storage and transportation, this study proposed a semi
      aqueous formulation that contains 2 mg/ml eptifibatide, 10% ethanol, 40%
      propylene glycol and 50% 0.025 M citrate buffer. The stability study was
      conducted in the pH range 4.25-6.25 under accelerated temperatures: 48, 60, 72.5
      degrees C. The results indicate that the proposed semi-aqueous vehicles
      substantially increased the drug stability in comparison with aqueous vehicles.
      The predicted drug shelf-life T(90) at 25 degrees C shows that an almost twofold
      increase can be achieved by formulating eptifibatide in the semi-aqueous vehicle,
      which is 60 months at its maximum stability of pH 5.75, as opposed to the 33
      months in the aqueous vehicle at its maximum stability of pH 5.25.

PMID- 11337149
TI  - Diffusive transport properties of some local anesthetics applicable for
      iontophoretic formulation of the drugs.
AB  - As part of a general study to improve the iontophoretic delivery of local
      anaesthetics of the amide type, the diffusion properties of the hydrochloride
      salts of bupivacaine, etidocaine, lidocaine, mepivacaine, prilocaine and
      ropivacaine, were studied in a 1% w/w agarose hydrogel. A source drug solution
      (25 mM) was placed in contact with the gel and, after an appropriate time, the
      drug concentration profile in the gel was analyzed to give a diffusion
      coefficient, D. The values of Dx10(10) expressed in m(2) s(-1) were: (bupi) 6.71,
      (eti) 6.71, (ropi) 6.39, (mepi) 7.31, (lido) 7.49 and (prilo) 7.76. For
      comparative reasons, the diffusion coefficient for LidHCl in an aqueous solution
      according to the Nernst-Hartley relation for the diffusion of ion-pairs was
      calculated, hereby taking into account ionic activity of LidH+ and Cl-. The
      diffusion coefficient thus obtained was 7.76x10(-10) m2 s-1 at infinite dilution.
      The relationship between the molecular weight of the compounds and the diffusion
      coefficient was investigated.

PMID- 11337150
TI  - Effects of molecular weight of polyvinylpyrrolidone on the glass transition and
      crystallization of co-lyophilized sucrose.
AB  - The purpose of the present study was to investigate the effects of molecular
      weight (MW) of polyvinylpyrrolidone (PVP) on glass transition and crystallization
      of sucrose. Thus, sucrose was co-lyophilized with 2.5 and 5.0% w/w PVP of
      different molecular weights, which were characterized using gel permeation
      chromatography. Freeze drying was carried out for 48 h at a shelf temperature of 
      40 degrees C and a pressure of about 36 Pa. The samples were then dried in a
      vacuum oven at 24 degrees C for 12 h before drying for a further 12 h at 40
      degrees C. Differential scanning calorimetry (DSC) was employed to measure the
      glass transition temperature (Tg), dynamic crystallization temperature (Tc) and
      isothermal crystallization induction time (tc) at 85 degrees C of sucrose.
      Isothermal water vapour sorption of each sample was also measured at different
      relative humidities. Tg values of sucrose varied from 48.3+/-0.8 degrees C for
      freeze-dried (FD) sucrose alone to 58.8+/-0.8 degrees C for the mixture
      containing 5.0% PVP of nominal MW 300 K. PVP increased sucrose T(g) significantly
      (ANOVA P<0.05). Although there was no significant difference (P>0.05) in Tg of
      the mixtures containing 2.5% w/w PVP of different MW, samples with 5.0% PVP of MW
      300 K produced a significantly higher (P<0.05) Tg than the other mixtures. All
      mixtures were shown to possess higher (P<0.01) Tc than FD sucrose alone, which
      exhibited a T(c) of approximately 85 degrees C. PVP of MW 300 K consistently
      induced a significantly (P<0.05) higher Tc of sucrose than PVP of smaller MW.
      Increasing PVP concentration from 2.5 to 5.0% also resulted in a substantial
      increase in sucrose Tc. Using isothermal water vapour absorption, sucrose tc was
      found to increase up to over 10 times when it was co-lyophilized with 2.5% PVP,
      the actual value of tc being dependent upon the MW of the PVP. For example, PVP
      of MW 300 K resulted in a sucrose tc at 85 degrees C (89.1-95.6 min), which was
      approximately seven times higher than that of 2.5% PVP of MW 24 or 40 K. A longer
      tc of sucrose was also observed for mixtures containing PVP of MW 300 K than when
      sucrose was mixed with PVP of smaller MW. Thus the effect of PVP on sucrose Tg,
      Tc and tc was found to be dependent upon MW. PVP of higher MW was more efficient
      in inhibiting sucrose crystallization and by stabilizing glassy structures of the
      sugar, these polymers may improve the stability of co-lyophilized proteins and
      peptides.

PMID- 11337151
TI  - Prolonged hypoglycemic effect of insulin-loaded polybutylcyanoacrylate
      nanoparticles after pulmonary administration to normal rats.
AB  - Insulin-loaded polybutylcyanoacrylate nanoparticles were prepared by emulsion
      polymerization. The mean diameter of the nanoparticles was 254.7 nm with a
      polydispersity of 0.064. The associating ratio of insulin to the nanoparticles
      reached 79.1%. Studies on in vitro release kinetics showed that release profiles
      can be modeled using a biexponential function and the burst effect was obvious.
      After various doses of insulin-loaded nanoparticles were intratracheally given to
      normal rats, significant decrease of glucose level was achieved at each dose
      group from 5 to 20 IU kg-1. The minimum blood glucose concentration reached
      46.9%, 30.4% and 13.6% of the initial level after pulmonary delivery of 5, 10 and
      20 IU kg-1 insulin-loaded nanoparticles to normal rats, respectively. The time to
      reach the minimum blood glucose level (Tmin) was 4, 4 and 8 h for three doses,
      respectively. The duration of glucose level below 80% of insulin-loaded
      nanoparticles was much longer than that of insulin solution at every dose.
      Relative pharmacological bioavailability of insulin-loaded nanoparticles by
      pulmonary administration was 57.2% over the same formulation by subcutaneous
      administration.

PMID- 11337152
TI  - Enhanced plasmid DNA transfection with lysosomotropic agents in cultured
      fibroblasts.
AB  - Transfer of plasmid DNA into mammalian cells has posed major challenges for gene
      therapy. Most non-viral vectors are known to internalize in the cells by
      endocytosis. Therefore, low transfection efficiency of non-viral vectors may be
      due to intracellular degradation of input DNA in the endosomes and/or lysosomes.
      DNA degradation can be inhibited either by inactivating the lysosomal enzymes or
      obliterating endosome fusion to lysosomes using lysosomotropic agents. We report
      here the effects of individual lysosomotropic agents such as chloroquine,
      polyvinylpyrolidone (PVP) and sucrose on beta-gal expression in cultured
      fibroblasts COS, 293 and CHO. Cell viability was influenced by type, exposure
      time and concentration of lysosomotropic agents. Exposure to chloroquine at high
      concentration (1000 microM) or more than 4 h at any concentration (10-1000
      microM) caused extensive cell death, however, cytotoxicity due to sucrose (5-500
      mM) and PVP (0.01-1 mg/ml) was minimal in the cell lines tested. All the agents
      utilized in this study enhanced the gene expression and the transfection
      efficiency followed the order of sucrose>chloroquine>PVP at the concentrations
      used in all cell lines. Results suggest that lysosomotropic agents can enhance
      transfection efficiency but the degree of transgene expression may be cell- and
      agent-specific. Of the agents studied, sucrose appears to be an attractive agent
      in improving gene expression without toxic effect in the cultured fibroblasts.
      Thus, it can be used as an excipient in the formulation of new gene delivery
      systems.

PMID- 11337153
TI  - Transdermal administration of salmon calcitonin by pulse depolarization
      iontophoresis in rats.
AB  - Using the pulse depolarization-iontophoresis (PDP-IP) system, salmon calcitonin
      (sCT), a drug for the treatment of osteoporosis, was transdermaly administered in
      rats. While absorption of sCT was not observed after passive transdermal
      administration, the serum sCT concentration was confirmed at a dose of 0.2-4
      microg when the PDP-IP system was employed. The results indicated that PDP-IP
      could enhance transdermal absorption of peptide drugs. Also noted was the
      increased amount of absorption of sCT along with an increase in the dose. We
      investigated the influence of electrical parameters (current, frequency) in PDP
      IP on the transdermal absorption of sCT. An optimal current for drug absorption
      was found within the range of transported current (0.1-1.0 mA) employed for PDP
      IP. In comparison with the results obtained at 0.1 mA, the drug absorption
      increased, along with an increase in transported current, when the current was
      set at 0.5 mA, while the drug absorption decreased at 1.0 mA in comparison. The
      decrease in drug absorption was assumed to be attributable to the structural
      destruction of skin by application of excessive current. There was no change in
      skin resistance attributable to the frequency; nor was there any influence of the
      frequency on the amount of drug absorption.

PMID- 11337154
TI  - Evaluation of a floating dosage form of nicardipine hydrochloride and
      hydroxypropylmethylcellulose acetate succinate prepared using a twin-screw
      extruder.
AB  - A floating dosage form composed of nicardipine hydrochloride (NH) and
      hydroxypropylmethylcellulose acetate succinate (enteric polymer) was prepared
      using a twin-screw extruder. By adjusting the position of the high-pressure screw
      elements in the immediate vicinity of die outlet, and by controlling the barrel
      temperature, we were able to prepare a puffed dosage form with very small and
      uniform pores. It was found that the porosity and pore diameter could be
      controlled by the varying amount of calcium phosphate dihydrate. In the shaking
      test, the puffed dosage form was found to have excellent floating ability and
      mechanical strength in acid solution (JP First Fluid, pH 1.2). The dissolution
      profile of NH was controlled by the amount of wheat starch. In the dissolution
      test using JP Second Fluid (pH 6.8), rapid dissolution of NH and loss of buoyancy
      were observed. It was shown that the puffed dosage form, consisting of enteric
      polymer prepared using the twin-screw extruder, was very useful as a floating
      dosage form that was retained for a long period in the stomach.

PMID- 11337155
TI  - Combined hydroxypropyl-beta-cyclodextrin and poly(alkylcyanoacrylate)
      nanoparticles intended for oral administration of saquinavir.
AB  - The aim of this study was to prepare and characterize an hydroxypropyl-beta
      cyclodextrin-saquinavir inclusion complex with the purpose of incorporating this
      complex into poly(alkylcyanoacrylate) nanoparticles in order to increase the drug
      loading. Hydroxypropyl-beta-cyclodextrin-saquinavir complex was characterized by
      thermal (differential scanning calorimetry), crystallographic (X-ray
      diffractography) and spectroscopic methods (circular dichroism, H1-NMR).
      Nanoparticles were prepared by polymerization of alkylcyanoacrylate monomers
      (isobutyl- and isohexylcyanoacrylate) in a water solution of the complex and
      further characterized. The apparent solubility of saquinavir was increased 400
      fold at pH 7.0 in presence of hydroxypropyl-beta-cyclodextrin owing to the
      formation of a drug-cyclodextrin complex as demonstrated mainly by 1H NMR and
      confirmed by other techniques. Saquinavir-loaded nanoparticles could be easily
      prepared in the presence of a drug-cyclodextrin complex. It was found that large
      amounts of cyclodextrins remained associated with the particles, resulting in a
      20-fold increase in saquinavir loading compared to nanoparticles prepared in the
      absence of cyclodextrins. This study has shown that the loading in saquinavir of
      poly(alkylcyanoacrylate) nanospheres could be dramatically improved by
      simultaneously increasing the apparent solubility of the drug in the preparation
      medium and the amount of cyclodextrin associated with the particles, making these
      nanospheres a promising system for oral application.

PMID- 11337156
TI  - Bioavailability of cyclosporin A dispersed in sodium lauryl sulfate-dextrin based
      solid microspheres.
AB  - The purpose of this work was to develop a solid dispersion system containing
      cyclosporin A (CsA) in order to improve the bioavailability of poorly water
      soluble CsA. Solid dispersion systems that are spherical in shape (CsA
      microspheres) were prepared with varying ratios of CsA/sodium lauryl
      sulfate/dextrin using a spray-drying technique. The effects of sodium lauryl
      sulfate (SLS) and dextrin on the dissolution of CsA dispersed in SLS-dextrin
      based solid microspheres were investigated. The bioavailability of CsA
      microspheres was compared with CsA powder alone and commercial Sandimmun in dogs.
      SLS significantly enhanced the dissolution of CsA from microspheres, while
      dextrin did not affect this. The CsA-microspheres at the CsA/SLS/dextrin ratio of
      1/3/1, which gave the highest dissolution rate of CsA among the formula treated,
      was selected as an optimal formula for oral delivery. This formula gave
      significantly higher blood levels, area under the drug concentration-time curve
      (AUC) and maximum blood concentration of drug (Cmax) of CsA in dogs compared with
      the CsA powder alone. The AUC, Cmax and time to reach maximum blood concentration
      (Tmax) of CsA with CsA-microspheres was not significantly different from those
      after oral administration of Sandimmun, suggesting the similar bioavailability to
      Sandimmun in dogs. Our study demonstrates that the CsA-microspheres prepared with
      SLS and dextrin, with improved bioavailability of CsA, would be useful to deliver
      a poorly water-soluble CsA and could be applicable to other poorly water-soluble
      drugs.

PMID- 11337157
TI  - Development and characterization of lipid microparticles as a drug carrier for
      somatostatin.
AB  - Somatostatin, a therapeutic peptide with a high therapeutical potential but a
      very short biological half-live was encapsulated within microparticles by a
      modified solvent evaporation method and a melt dispersion method without the use
      of organic solvent. As the use of synthetic polymer matrix materials often goes
      along with detrimental effects on incorporated peptides, we investigated the
      potential of physiological lipids such as glyceryl tripalmitate (Dynasan 116) as
      an alternative matrix material. The two preparation methods were evaluated with
      respect to surface topography, particle size distribution, encapsulation
      efficiency, in-vitro release behavior and modification of the resulting
      microparticles. Microparticles with a suitable particle size distribution for
      i.m. or s.c. injection could be prepared with both methods. The encapsulation
      efficiency of the peptide into glyceryl tripalmitate microparticles was
      substantially influenced by the preparation method and the physical state of the
      peptide to be incorporated. The melt dispersion technique and the incorporation
      of the drug as an aqueous solution gave the best results with actual drug
      loadings up to 9% and an encapsulation efficiency of approximately 90%.
      Microparticles prepared by the melt dispersion technique crystallized in the
      unstable alpha-modification. The peptide was released almost continuously over 10
      days with no burst effect, 20-30% of the incorporated somatostatin was not
      released in the monitored time period.

PMID- 11337158
TI  - Investigation of the felodipine glassy state by atomic force microscopy.
AB  - The glassy state of felodipine was prepared by melting crystals of felodipine on
      a clean glass slide and cooling to room temperature. It has been confirmed that
      glassy felodipine is a metastable state, and undergoes transformation to the more
      stable crystalline form. Crystallization occurred slowly and spontaneously at
      room temperature, below the glassy state transition temperature (Tg). The contact
      mode of atomic force microscopy was used for topographical imaging of the glassy
      and crystalline states of felodipine. When the glassy felodipine region next to
      the recrystallized zone was exposed to controlled mechanical stress through the
      tip, rapid additional crystallization was observed. This crystallization process
      can be induced and imaged in real time by atomic force microscopy.

PMID- 11337159
TI  - On the difficulty of assessing the specific surface area of magnesium stearate.
AB  - The water content of as-received commercial magnesium stearate batches from
      animal and vegetable sources have been modified by ageing in humid air at room
      temperature or by vacuum treatment. The complete adsorption-desorption isotherms
      of nitrogen and krypton vapours by samples of these as received and modified
      materials have been measured at liquid nitrogen temperature after standardised
      vacuum degassing. They are greatly affected by the initial water content of the
      material. In particular: (a) the BET surface area values computed from the
      adsorption branch vary widely and is increasing with increasing water content;
      (b) anomalous hysteresis of varying amplitude is observed in all cases except
      adsorption of krypton on the material with the lowest water content; (c) the
      hysteresis loops extend down to very low desorption pressure values and cannot be
      accounted for by capillary condensation. Lastly, the surface area value of a
      given material computed from nitrogen and krypton adsorption may differ by a
      factor as high as six. Accordingly, the very significance of BET surface area
      values obtained from routine adsorption experiments should be regarded as
      questionable, at least until the mechanisms of adsorption are fully clarified.

PMID- 11337161
TI  - Targeted drug delivery systems 6: Intracellular bioreductive activation, uptake
      and transport of an anticancer drug delivery system across intestinal Caco-2 cell
      monolayers.
AB  - We demonstrate transport across, intracellular accumulation and bioreductive
      activation of a conformationally constrained, anticancer drug delivery system
      (the CH(3)-TDDS) using Caco-2 cell monolayers (CCMs) as an in vitro model of the
      human intestinal mucosa. Reverse-phase High Performance Liquid Chromatography
      (HPLC) coupled with UV detection was used to detect CH(3)-TDDS, the bioreduction
      product (lactone) and the released drug (melphalan methyl ester; MME). Upon
      incubation of the CH(3)-TDDS with the apical (AP) surface of 21-day-old CCM, we
      observed rapid decrease in the AP concentration of the CH(3)-TDDS (60%/hr) as a
      result of cellular uptake. Rapid intracellular accumulation of the CH(3)-TDDS was
      followed by bioreductive activation to deplete the cellular levels of CH(3)-TDDS.
      The drug part (MME) and lactone, as well as CH(3)-TDDS, were detected in the
      basolateral (BL) chamber. Intracellular Caco-2 levels of TDDS and lactone were
      also detectable. Bioreductive activation of the CH(3)-TDDS was additionally
      confirmed by formation of lactone after incubation of the CH(3)-TDDS in the
      presence of freshly prepared Caco-2 cell homogenates. During transport studies of
      melphalan or MME alone (as control), the intact drug was not detected in the
      intracellular compartment or in the BL chamber. These observations demonstrate
      that CH(3)-TDDS has potential for improving intestinal delivery of MME. TDDS
      could be useful in facilitating oral absorption of MME as well as the oral
      delivery of other agents.

PMID- 11337162
TI  - Effect of ethanol and isopropyl myristate on the availability of topical
      terbinafine in human stratum corneum, in vivo.
AB  - PURPOSE: The objective of this study was to determine the availability of the
      topical drug terbinafine (TBF) in human stratum corneum (SC) in vivo following
      its administration in formulations containing isopropyl myristate and ethanol.
      METHODS: The ventral forearms of human volunteers were treated for 4 h with TBF,
      at a concentration equal to 1/4 saturation, in isopropyl myristate (IPM), in
      ethanol (EtOH) and in 50:50 v/v IPM/EtOH. At the end of the application period,
      the treated sites were carefully cleaned of excess vehicle and the SC was
      progressively removed by sequential tape stripping. TBF was quantified in the SC
      by: (a) extraction of the tape strips and subsequent HPLC analysis; and (b)
      attenuated total reflectance infrared spectroscopy (ATR-FTIR) of each
      sequentially exposed SC surface during the tape stripping procedure. RESULTS: The
      concentration profile of TBF in the SC (i.e. drug concentration as a function of
      depth in the membrane) was fitted to the appropriate solution of Fick's second
      law of diffusion, allowing thereby the drug's SC/vehicle partition coefficient
      (K) and characteristic diffusion parameter (D/L(2), where D is the diffusivity of
      TBF in the SC of thickness L) to be deduced. CONCLUSIONS: While D/L(2) for TBF
      derived from the three vehicles remained essentially constant, the drug's
      partitioning into the SC was significantly higher from formulations containing
      ethanol. Both the semi-quantitative infrared data and the more rigorous HPLC
      results supported these deductions.

PMID- 11337163
TI  - Physicochemical assessments of parenteral lipid emulsions: light obscuration
      versus laser diffraction.
AB  - The United States Pharmacopeia (USP) has proposed a new Chapter <729> entitled
      'Globule Size Distribution in Intravenous Emulsions' that is intended to identify
      methods for analyzing the stability of lipid emulsions. We studied the
      differences between particle-sizing instruments when analyzing the
      physicochemical stability of a parenteral nutrition mixture compounded with
      intravenous lipid emulsion, known as an all-in-one mixture. As the growth of
      lipid droplets, i.e. coalescence, signals an irreversible change in emulsion
      stability, we focused our investigation on the large diameter tail (>5 microm) of
      the globule size distribution. Of the four proposed methods, droplet size was
      studied over a range of mixture stabilities using a low osmolality parenteral
      nutrition formula employing both light scattering and light obscuration
      techniques. In addition, the same mixtures were also freshly prepared, and then
      spiked with a known amount of 5 microm latex spheres. The response obtained from
      the light obscuration technique was linear and detected both unstable and latex
      spiked mixtures in every case for droplets or particles >5 microm. The results of
      the laser diffraction method were non-linear and overestimated, was less
      sensitive or missed entirely, globules or particles in the large diameter tail of
      the dispersion. The results demonstrate that light obscuration is superior to
      laser diffraction in identifying unstable intravenous fat emulsions.

PMID- 11337164
TI  - Characterization of the hydroxypropylmethylcellulose-nicotinamide binary system.
AB  - The effect of hydroxypropylmethylcellulose (HPMC) on the thermal behaviour of
      nicotinamide was studied. Binary mixtures of nicotinamide and HPMC, composed of
      various weight fractions of HPMC (X(HPMC)), were heated, cooled and subsequently
      re-heated. HPMC dissolved in fused nicotinamide at 140 degrees C. The binary
      mixture at compositions 0<==X(HPMC)<==0.3 formed a film structure on cooling. At
      X(HPMC)>==0.4, the molten nicotinamide at 140 degrees C was saturated with HPMC.
      These heated mixtures did not form a homogeneous film by cooling to ambient
      temperature. At X(HPMC)<0.4, differential scanning calorimetry peaks originating
      from recrystallization and melting of nicotinamide were observed in the cooling
      and re-heating scans, respectively. These peaks became smaller with increase in
      X(HPMC) and disappeared at X(HPMC) approximately 0.4. Decrease in crystallinity
      with increase in X(HPMC) was confirmed by X-ray diffraction. The glass transition
      temperature of the cooled mixture (T(g)) increased with increase in X(HPMC). When
      the enthalpy of melting of nicotinamide and 1/T(g) were plotted against X(HPMC),
      inflections were observed at similar X(HPMC) values, 0.37-0.38. Dissolution of
      HPMC in molten nicotinamide was accompanied by hydrogen bond formation, which was
      confirmed by infrared studies.

PMID- 11337165
TI  - Formulation of a reservoir-type testosterone transdermal delivery system.
AB  - A reservoir-type transdermal delivery system of testosterone (TS) was developed
      using an ethanol/water (70:30) cosolvent system as the vehicle. The maximum
      permeation rate achieved by 70% (v/v) of ethanol was further increased from 2.69
      to 47.83 microg/cm(2)/h with the addition of 1.0% dodecylamine as the skin
      permeation enhancer. The permeation rate of TS through the ethylene vinyl acetate
      (EVA) membrane was observed to increase as the vinyl acetate content in the
      copolymer increased. Addition of 1.0% (w/w) gelling agent, hydroxypropyl
      methlycellulose (HPMC), in the reservoir formulation resulted in desirable
      rheological properties with an insignificant effect on the skin permeation rate
      of TS. Thus, a new transdermal delivery system for TS was formulated using EVA
      membrane coated with a pressure-sensitive adhesive (Duro-Tak 87-2510) and HPMC as
      a gelling agent. This experimental patch showed comparable plasma concentration
      profiles in the in vivo study when compared with a commercial product,
      Androderm(R). Moreover, the results suggested the possibility of further
      enhancing the permeation rate of TS by controlling the composition of the
      reservoir formulation.

PMID- 11337166
TI  - Effect of liposomes and niosomes on skin permeation of enoxacin.
AB  - The skin permeation and partitioning of a fluorinated quinolone antibacterial
      agent, enoxacin, in liposomes and niosomes, after topical application, were
      elucidated in the present study. In vitro percutaneous absorption experiments
      were performed on nude mouse skin with Franz diffusion cells. The influence of
      vesicles on the physicochemical property and stability of the formulations were
      measured. The enhanced delivery across the skin of liposome and niosome
      encapsulated enoxacin had been observed after selecting the appropriate
      formulations. The optimized formulations could also reserve a large amount of
      enoxacin in the skin. A significant relationship between skin permeation and the
      cumulative amount of enoxacin in the skin was observed. Both permeation enhancer
      effect and direct vesicle fusion with stratum corneum may contribute to the
      permeation of enoxacin across skin. Formulation with niosomes demonstrated a
      higher stability after 48 h incubation compared to liposomes. The inclusion of
      cholesterol improved the stability of enoxacin liposomes according to the results
      from encapsulation and turbidity. However, adding negative charges reduced the
      stability of niosomes. The ability of liposomes and niosomes to modulate drug
      delivery without significant toxicity makes the two vesicles useful to formulate
      topical enoxacin.

PMID- 11337167
TI  - Evaluation of creams and ointments as suitable formulations for peldesine.
AB  - In-vitro studies were conducted to study the efficacy of mixed and self
      emulsifying creams and hydrophobic ointment formulations in delivering peldesine
      (BCX-34) into and across cryopreserved human cadaver skin (HCS). Oil-in-water
      cream formulations, containing 1% w/w of radiolabeled C(14) BCX-34 and propylene
      glycol (PG), glycerin (GLY), isopropyl myristate (IPM), oleic acid (OA) and
      capric-caprylic esters (CE) were prepared. Petrolatum and lanolin based ointments
      were also prepared with PG. Sections of the HCS, 250 microm thick, were fitted to
      vertical Franz diffusion chambers containing a receptor medium of pH 7.4
      phosphate buffer solution maintained at 37 degrees C. Using the finite dose
      technique, 4-6 mg of a formulation sample was applied to the epidermal surface of
      each section and drug diffusion was permitted for 12 and 24 h periods. The
      distribution of drug into the HCS epidermis, dermis and into the receptor medium
      was measured by scintillation spectroscopy. The results show good correlation of
      the calculated in-vitro values for flux and skin-vehicle partition coefficients
      against the observed amounts of drug detected in the HCS. The mixed emulsion
      cream formulation containing PG delivered higher amounts of drug into the skin
      when compared to the same formulation containing GLY cream. The self-emulsifying
      cream formulation containing IPM had a higher skin-vehicle partition coefficient
      and delivered more drug into the dermis when compared to those formulations that
      contained OA and CE. The petrolatum ointment delivered six times more drug into
      the epidermis than the lanolin ointment, and had higher skin-vehicle partition
      values. In conclusion, creams containing PG and petrolatum-base formulations
      would be suitable for BCX-34 dermal delivery.

PMID- 11337168
TI  - An oral controlled release matrix pellet formulation containing nanocrystalline
      ketoprofen.
AB  - A controlled release pellet formulation using a NanoCrystal colloidal dispersion
      of ketoprofen was developed. In order to be able to process the aqueous
      NanoCrystal colloidal dispersion into a hydrophobic solid dosage form a spray
      drying procedure was used. The in vitro dissolution profiles of wax based pellets
      loaded with nanocrystalline ketoprofen are compared with the profiles of wax
      based pellets loaded with microcrystalline ketoprofen and of a commercial
      sustained release ketoprofen formulation. Pellets were produced using a melt
      pelletisation technique. All pellet formulations were composed of a mixture of
      microcrystalline wax and starch derivatives. The starch derivatives used were
      waxy maltodextrin and drum dried corn starch. Varying the concentration of drum
      dried corn starch increased the release rate of ketoprofen but the ketoprofen
      recovery remained problematic. To increase the dissolution yield surfactants were
      utilised. The surfactants were either added during the production process of the
      NanoCrystal colloidal dispersion (sodium laurylsulphate) or during the pellet
      manufacturing process (Cremophor RH 40). Both methods resulted in a sustained but
      complete release of nanocrystalline ketoprofen from the matrix pellet
      formulations.

PMID- 11337169
TI  - The influence of vacuum mixing on methylmethacrylate liberation from acrylic
      cement powder.
AB  - Polymethylmethacrylate (PMMA) bone cement is a biomaterial used to anchor
      prostheses during joint replacement surgery. Residual methylmethacrylate monomer
      (MMA) may be related with the cytotoxic effect of PMMA. The aim of the present
      paper was to investigate the effect of two different cement mixing methods: hand
      stirring at atmospheric pressure and under partial vacuum (0.330 and 0.154 bar)
      on residual monomer liberation in phosphate buffer saline solution from acrylic
      cement powder. Residual MMA content was determined by high-performance liquid
      chromatography. Mathematical models were applied to experimental dissolution data
      revealing that monomer release was significantly reduced in bone cement powder
      obtained at 0.154 bar vacuum pressure compared to the other mixing conditions.
      The kinetic models applied are consistent with a simple diffusion mechanism of
      the monomer from the polymer matrix.

PMID- 11337170
TI  - Transdermal delivery of naloxone: effect of water, propylene glycol, ethanol and
      their binary combinations on permeation through rat skin.
AB  - The effect of the solvent systems water, ethanol (EtOH), propylene glycol (PG)
      and their binary combinations was studied on the ex vivo permeation profile of
      the opioid receptor antagonist, naloxone, through rat skin. Fourier transform
      infrared (FT-IR) spectroscopic studies were done to investigate the effect of
      enhancers on the biophysical properties of the stratum corneum (SC), in order to
      understand the mechanism of permeation enhancement of naloxone by the solvent
      systems used. The flux of naloxone was found to increase with increasing
      concentrations of EtOH, upto 66% in water, and PG upto 50% in water. The maximum
      flux of 32.85 microg cm(-2) h(-1) was found with 33% PG in EtOH. The FT-IR
      spectra of SC treated with EtOH showed peak broadening at 2920 cm(-1) at all
      concentrations of EtOH studied indicating that EtOH increases the translational
      freedom (mobility) of lipid acyl chains. Theoretical blood levels well above the
      therapeutic concentration of naloxone can be achieved with the solvent system
      comprising 33% PG in EtOH and hence, provides flexibility in choice of patch size
      depending on the addiction status of the patient to be treated.

PMID- 11337171
TI  - Electric field analysis on the improved skin concentration of benzoate by
      electroporation.
AB  - The objective in the present study was to understand the relationship between the
      increased skin concentration of benzoate as a model drug after topical
      application of its sodium salt and the electric field intensity produced in the
      skin barrier, the stratum corneum, by electroporation. A piece of excised
      abdominal hairless rat skin was set in a Franz type diffusion cell, and 0.5%
      sodium benzoate and physiological saline were applied to the stratum corneum and
      dermis sides, respectively. Two needle electrodes made of Ag were connected to an
      electrical power source, which produced exponentially decaying pulses. The
      electrodes were placed on the skin surface with a distance of 0.5 cm between both
      electrodes. After the 4 h passive permeation experiment, an electrical pulse was
      applied to the rat skin at 300 V every minute for 10 min. The skin was then
      removed from the diffusion cell, and the amounts of benzoate in different
      positions of the skin specimen were measured. Field intensity generated in the
      stratum corneum by electroporation was determined by a finite element method
      using a computer program. The amounts of benzoate at different sites in the skin
      were almost proportional to the mean field intensity in the corresponding stratum
      corneum. These results suggested that the enhancing effect of electroporation can
      be evaluated by the field intensity more directly than the application voltage.

PMID- 11337172
TI  - Drying behaviour of two sets of microcrystalline cellulose pellets.
AB  - The objective was to study contraction and densification of two sets of
      microcrystalline cellulose pellets, prepared using water (W) or a 25/75% w/w
      water/ethanol (W/E) mixture, during drying. The pellets were dried on microscope
      slides, photographed and weighed at set times. The porosity of the dry pellets
      was determined by mercury pycnometry. From pellet size, weight and porosity data,
      contraction and densification of the pellets and the relationship of these to the
      liquid content of the pellets during drying were calculated. Both types of
      pellets contracted and densified during drying. The initial porosity was similar
      for both types, but the final porosity of the dry pellets was higher for the W/E
      pellets. Thus, the difference in final pellet porosity between the two types was
      caused by a difference in densification during drying rather than a different
      degree of densification during the pelletisation procedure. The contraction rate
      and the relationships between contraction and the volume of removed liquid, and
      contraction and the degree of liquid saturation differed between the two types of
      pellet. The difference in drying behaviour between the two types of pellets can
      be explained by a liquid related change in both contraction driving force and
      contraction counteracting force or by a different contraction mechanism.

PMID- 11337173
TI  - Preparation of gelatin microparticles by co-lyophilization with poly(ethylene
      glycol): characterization and application to entrapment into biodegradable
      microspheres.
AB  - Gelatin microparticles were prepared by co-lyophilization with poly(ethylene
      glycol) (PEG) as a protein micronization adjuvant. Aqueous solutions containing
      gelatin and PEG at various mixing ratios were freeze-dried. The lyophilizates
      were dispersed in methylene chloride and subjected to particle size analysis. The
      particle size decreased as the PEG/gelatin ratio increased. The microparticles
      isolated from the suspension had spherical microdomains with sizes ranging from 1
      to 10 microm, which indicated that phase separation between PEG and gelatin
      during freezing was involved in the formation mechanism of gelatin
      microparticles. By using this technology, gelatin microparticles with an average
      size of less than 10 microm, with high purity of more than 90% and with good
      dispersibility could be obtained with high yield. The gelatin microparticles with
      average sizes from 5 to 20 microm were applied to encapsulation into
      biodegradable PLGA/PLA microspheres via a solid-in-oil-in-water emulsion process.
      The entrapment efficiency was highly dependent on the particle size and the size
      distribution, signifying that solid microparticles with an average diameter of
      less than 5 m and an maximal diameter of less than 10 microm would be required
      for effective encapsulation. These gelatin microparticles would be useful for
      studying and developing various drug delivery systems.

PMID- 11337174
TI  - Liposomal gels for vaginal drug delivery.
AB  - The aim of our study was to develop a liposomal drug carrier system, able to
      provide sustained and controlled release of appropriate drug for local vaginal
      therapy. To optimise the preparation of liposomes with regards to size and
      entrapment efficiency, liposomes containing calcein were prepared by five
      different methods. Two optimal liposomal preparations (proliposomes and polyol
      dilution liposomes) were tested for their in vitro stability in media that
      simulate human vaginal conditions (buffer, pH 4.5). To be closer to in vivo
      application of liposomes and to achieve further improvement of their stability,
      liposomes were incorporated in vehicles suitable for vaginal self-administration.
      Gels of polyacrylate were chosen as vehicles for liposomal preparations. Due to
      their hydrophilic nature and bioadhesive properties, it was possible to achieve
      an adequate pH value corresponding to physiological conditions as well as
      desirable viscosity. In vitro release studies of liposomes incorporated in these
      gels (Carbopol 974P NF or Carbopol 980 NF) confirmed their applicability as a
      novel drug carrier system in vaginal delivery. Regardless of the gel used, even
      24 h after the incubation of liposomal gel in the buffer pH 4.5 more than 80% of
      the originally entrapped substance was still retained.

PMID- 11337175
TI  - Design of a core-shelled polymer cylinder for potential programmable drug
      delivery.
AB  - A cylindrical dosage form comprising a laminated composite polymer core and a
      hydrophobic polycarbonate coating was proposed for programmable drug delivery. In
      the core, poly[(ethyl glycinate) (benzyl amino acethydroxamate) phosphazene] was
      synthesized as drug-loaded layers for its strong pH-sensitive degradation (eroded
      after 1.5 days at pH 7.4 and more than 20 days at pH 5.0 and 6.0). Poly(sebacic
      anhydride)-b-polyethylene glycol or poly(sebacic anhydride-co
      trimellitylimidoglycine)-b-poly(ethylene glycol) was selected as isolating layers
      for their good processing properties at room temperature and suitable erosion
      duration. The in vitro drug release studies of these devices were conducted under
      physiological conditions (pH 7.4). The results revealed that the model drugs
      (brilliant blue, FITC-dextran, myoglobin) could be released in typical pulsatile
      manner. Moreover, the duration time of drug release (24-40 h) and the lag time
      (18-118 h) could be separately regulated by the mass of polyphosphazene and the
      type or mass of polyanhydride. In this experiment, the cooperative effect of
      polyanhydrides and pH-sensitive degradable polyphosphazene was specially
      demonstrated, which offers a new idea to develop a programmable drug delivery
      system for single dose vaccine and other related applications.

PMID- 11337176
TI  - Mechanistic study into the enhanced transdermal permeation of a model beta
      blocker, propranolol, by fatty acids: a melting point depression effect.
AB  - Transdermal permeation of propranolol through human skin in the presence of fatty
      acid (lauric, capric) penetration enhancers has been investigated. Thermal
      analysis showed that binary mixtures of propranolol with either fatty acid were
      not simple mechanical mixtures of the two components. Propranolol formed 1:1
      molar addition compounds with both lauric and capric acids; the addition compound
      produced from propranolol and lauric acid (m.p. 79 degrees C) also developed
      eutectic systems with both propranolol (m.p. 54 degrees C) and lauric acid (m.p.
      16 degrees C). Similarly, the addition compound made from propranolol and capric
      acid (m.p. 97 degrees C) formed eutectic systems with propranolol (m.p. 83
      degrees C) and capric acid (m.p. 15 degrees C). Infrared analyses indicated that
      the addition compounds were fatty acid salts of the beta-blocker. The nature of
      the species permeating through human epidermal membranes from binary mixtures of
      propranolol with the fatty acids was investigated using a novel attenuated total
      reflectance Fourier transform infrared method. There was no clear difference in
      permeation rates of the fatty acids compared with the beta-blocker, suggesting
      that the permeating species was the intact addition compound. The influence of
      melting point depression of the beta-blocker fatty acid systems on transdermal
      permeation was predicted from a mathematical model; predicted and experimentally
      determined data correlated well thus providing an alternative explanation as to
      the mode of action of these permeation enhancers.

PMID- 11337177
TI  - Effect of menthone on the in vitro percutaneous absorption of tamoxifen and skin
      reversibility.
AB  - The effect of penetration enhancer (i.e., 1, 2, 3 and 5% menthone in combination
      with 50% ethanol (EtOH)) was investigated on the in vitro percutaneous absorption
      of tamoxifen, and post-recovery epidermal permeability after removal of the above
      enhancer. The flux of tamoxifen with menthone in combination with 50% EtOH was
      significantly greater (P<0.05) than the control (50% EtOH). The flux of tamoxifen
      increased with increasing concentrations of menthone. The post-recovery flux
      through enhancer exposed epidermis was significantly decreased (P<0.05) as
      compared to pre-recovery. However, post-recovery flux of tamoxifen through the
      enhancer-exposed epidermis did not completely recover to the baseline (i.e., post
      recovery flux through phosphate buffered saline, pH 7.4 treated epidermis).

PMID- 11337179
TI  - Correlation between detection methods of Chlamydia pneumoniae in atherosclerotic
      and non-atherosclerotic tissues.
AB  - Polymerase chain reaction (PCR) and immunohistochemistry (IHC) have been used to
      detect Chlamydia (C.) pneumoniae in vascular tissues. Discrepancies between the
      results of these two methods have frequently been reported. However, the
      correlation between PCR and IHC has not been analyzed yet. This study assesses
      the correlation between the detection of C. pneumoniae by PCR and IHC in 45
      atherosclerotic and 50 non-atherosclerotic tissue specimens. Also, the presence
      of Mycoplasma (M.) pneumoniae in these 95 specimens was investigated. Correlation
      was found between the detection of C. pneumoniae by PCR and IHC in the
      atherosclerotic tissues. Both tests were positive in 10 specimens and negative in
      17 specimens (p = 0.003). There was no significant correlation between PCR and
      IHC in non-atherosclerotic specimens (p = ns). M. pneumoniae was detected, by
      PCR, in one atherosclerotic specimen.The results show correlation between PCR and
      IHC in the detection of C. pneumoniae in atherosclerotic tissues, emphasize the
      association between C. pneumoniae and atherosclerosis, and support the
      specificity of the association between C. pneumoniae and atherosclerosis.

PMID- 11337180
TI  - Occurrence of the vanA and vanC2/C3 genes in Enterococcus species isolated from
      poultry sources in Malaysia.
AB  - Enterococcus species isolated from poultry sources were characterized for their
      resistance to antibiotics, plasmid content, presence of van genes and their
      diversity by randomly amplified polymorphic DNA-polymerase chain reaction (RAPD
      PCR). The results showed that all isolates were multi-resistance to the
      antibiotics tested. Ampicillin (15/70) followed by chloramphenicol (37/70) were
      the most active antibiotics tested against the Enterococcus spp. isolates, while
      the overall resistant rates against the other antibiotics were between 64.3% to
      100%. All vancomycin-resistant E. faecalis, E. durans, E. hirae and E. faecium
      isolates tested by the disk diffusion assay were positive in PCR detection for
      presence of vanA gene. All E. casseliflavus isolates were positive for vanC2/C3
      gene. However, none of the Enterococcus spp. isolates were positive for vanB and
      vanC1 genes. Plasmids ranging in sizes between 1.1 to ca. 35.8 MDa were detected
      in 38/70 of the Enterococcus isolates. When the genetic relationship among all
      isolates of the individual species were tested by RAPD-PCR, genetic differences
      detected suggested a high genetic polymorphisms of isolates in each individual
      species. Our results indicates that further epidemiological studies are necessary
      to elucidate the role of food animals as reservoir of VRE and the public health
      significance of infections caused by Enterococcus spp.

PMID- 11337181
TI  - Detection of Candida spp. in blood cultures using nucleic acid sequence-based
      amplification (NASBA).
AB  - Candida spp. are the main causes of fungal infections in immunocompromised
      patients. It is known, that the routinely used automated blood culture systems
      may fail to detect yeasts. We therefore investigated, whether Nucleic Acid
      Sequence-Based Amplification (NASBA) can be used to improve the detection rate of
      Candida spp. in blood cultures. Culture-positive as well as negative blood
      cultures from patients with a proven candidaemia were analyzed, and the results
      of BacT/Alert monitoring were compared with the results of NASBA-based detection
      of yeast RNA. With the NASBA-assay, the number of positive blood cultures
      increased from 21% to 34%. The NASBA-assay may confirm the diagnosis and
      demonstrate the need for prolonged treatment. In addition it may shorten the time
      to detection. In summary, using NASBA for the detection of yeast RNA in blood
      cultures, we have shown for the first time that it is possible to improve the
      detection rate of yeasts in blood cultures by using amplification technology.

PMID- 11337182
TI  - Trichosporon species infection in bone marrow transplanted patients.
AB  - Trichosporon species are emerging as opportunistic agents that cause systemic
      diseases in immunocompromised patients. Patients undergoing bone marrow
      transplant are submitted to intense and prolonged periods of neutropenia and
      consequently to several risk factors to fungal infections as the use of broad
      spectrum antibiotics and invasive devices. Two cases of fungal infections caused
      by Trichosporon asahii var. asahii and T. inkin in patients with bone marrow
      transplant are described T. asahii var. asahii was responsible for fungemia and
      the identification of this microorganism was later performed. T. inkin caused
      vascular accesses infection and was recovered from an implanted Hickman-Broviac
      catheter. Both patients were under oral fluconazole prophylaxis. The patient with
      systemic infection died despite the therapy with amphotericin B and the patient
      with catheter-related infection recovered from the fungal infection after
      catheter removal. Difficulties in the identification of this microorganism lead
      to delays in treatment and post-mortem diagnosis.

PMID- 11337183
TI  - First isolation of Candida dubliniensis in Rio Grande do Sul, Brazil.
AB  - Candida dubliniensis is a newly recognized species closely phylogenetically
      related to Candida albicans and is commonly associated with oral candidiasis in
      human immunodeficiency virus-positive patients. In this paper we report the
      isolation of three strains of C. dubliniensis, from AIDS patients, in the state
      of Rio Grande do Sul (Brazil). The phenotypic identification was based on germ
      tube emission, abundant production of chlamydospores, assimilation of sucrose but
      not of xylose and the inability to grow at 42 degrees C. Randomly amplified
      polymorphic DNA (RAPD) analysis and genomic DNA sequencing confirmed the distinct
      genetic nature C. dubliniensis. Topics related to the epidemiology, isolation,
      phenotypical and genotypical identification of C. dubliniensis are also
      discussed.

PMID- 11337184
TI  - Enzyme-linked immunosorbent assay with Trypanosoma cruzi excreted-secreted
      antigens (TESA-ELISA) for serodiagnosis of acute and chronic Chagas' disease.
AB  - In the present report we describe the use of Trypomastigote Excreted-Secreted
      Antigens (TESA) as antigen in ELISA for Chagas' disease serodiagnosis. The study
      was carried out on 284 patients, 164 of whom were nonchagasic subjects including
      individuals with leishmaniasis or other pathologies, and 120 chagasic patients,
      being 53 in the acute (with positive IgA and IgM antibodies to T. cruzi) and 67
      in the chronic phase. TESA-ELISA showed 100% positivity in the survey of IgG
      antibodies in chagasic patients (acute and chronic) and 100% positivity for IgM
      antibodies in acute phase sera. TESA preparation does not require biochemical
      purification procedures and does not present the cross-reactivity of
      leishmaniasis sera observed when ELISA with epimastigote alkaline extract (EAE)
      is performed. ELISA competition assays showed that anti-T. cruzi antibodies of
      sera from chagasic patients that react with TESA are different from those that
      react with EAE. Besides, partial characterization of TESA showed that several
      epitopes present in this fraction are absent in EAE.

PMID- 11337185
TI  - In vitro susceptibility of recent clinical isolates of Chlamydia trachomatis to
      macrolides and tetracyclines.
AB  - We tested the in vitro activity of clarithromycin, azithromycin, roxithromycin,
      erythromycin, doxycycline, and tetracycline against 50 clinical isolates of
      Chlamydia trachomatis. The minimal inhibitory concentrations (MICs) and the
      minimal bactericidal concentrations (MBCs) were determined in a tissue culture
      system using cycloheximide treated McCoy cells. MIC values for all the isolates
      were < or =0.015 microg/ml for clarithromycin, < or =0.125 microg/ml for
      roxithromycin and azithromycin, and < or =0.25 microg/ml for erythromycin and
      doxycycline. Almost half of the isolates (44%) were inhibited only by a
      concentration of 0.5 microg/ml of tetracycline. MBC as high as 4 microg/ml was
      displayed by doxycycline and tetracycline against 8% and 4% of the isolates
      respectively of the agents recommended by the Center for Disease Control as drugs
      of choice for the treatment of chlamydial infections, azithromycin exhibited a
      markedly better in-vitro activity than did erythromycin and doxycycline.

PMID- 11337186
TI  - Comparative serum bactericidal activity of clarithromycin and azithromycin
      against macrolide-sensitive and resistant strains of Streptococcus pneumoniae.
AB  - The serum pharmacodynamics of clarithromycin and azithromycin were studied
      against isolates of S. pneumoniae, including efflux resistant (M. phenotype)
      strains, by analyzing their serum bactericidal activity (SBA) over time. Normal
      healthy subjects were given a single 500 mg oral dose of these macrolides and
      serum samples were collected over 12 hrs. Paired isolates with MICs ranging from
      0.25 ug/ml to 8.0 ug/ml were analyzed. Prolonged (at least 6 hrs) SBA was
      observed with clarithromycin for strains with MICs < or = 2.0 ug/ml. No SBA was
      observed in strains with MICs >or = 4.0 ug/ml. Azithromycin exhibited SBA for at
      least 6 hrs for strains up to a MIC = 0.5 ug/ml. No SBA was observed for isolates
      with MICs > or = 1.0 ug/ml. In contrast to azithromycin, clarithromycin exhibited
      SBA for at least one-half of its normal dosing interval against S. pneumoniae
      strains well above its current susceptibility breakpoint concentration of 0.25
      microg/ml. These findings may have relevance to the ongoing debate as to the
      appropriate susceptibility breakpoints for the newer macrolides.

PMID- 11337187
TI  - Prevalence and phenotypes of erythromycin-resistant Streptococcus pneumoniae in
      Shanghai, China.
AB  - Bacterial resistance of Streptococcus pneumoniae against erythromycin and
      clindamycin and resistance phenotypes of erythromycin-resistant Streptococcus
      pneumoniae were investigated. The MICs of erythromycin and clindamycin against
      345 strains of Streptococcus pneumoniae were tested with agar dilution method;
      the phenotypes of erythromycin-resistant Streptococcus pneumoniae were detected
      by double-disk test. One hundred and eighty-three and 171 of 345 (53.0% and
      49.6%) of isolates had MICs > or =1 microg/ml for erythromycin and for
      clindamycin. Among erythromycin-resistant Streptococcus pneumoniae, the
      percentage of cMLS, iMLS and M phenotype was 90.3% (159/176), 5.7% (10/176) and
      4.0% (7/176), respectively. The incidence of erythromycin-resistant Streptococcus
      pneumoniae is very high in Shanghai. The main phenotype is cMLS.

PMID- 11337188
TI  - Cutaneous leucocytoclastic vasculitis associated with oxacillin.
AB  - A 67-year-old man who was treated with oxacillin for one week because of
      Staphylococcus aureus bacteremia, developed renal failure and diffuse, symmetric,
      palpable purpuric lesions on his feet. Necrotic blisters were noted on his
      fingers. Skin biopsies showed findings diagnostic of leucocytoclastic vasculitis.
      Oxacillin was discontinued and patient was treated with corticosteroids. The rash
      disappeared after three weeks and renal function returned to normal.
      Leucocytoclastic vasculitis presents as palpable purpura of the lower extremities
      often accompanied by abdominal pain, arthralgia, and renal involvement. Etiologic
      factors or associated disorders include infections, medications, collagen
      vascular disease and neoplasia. However, in half of the cases no etiologic factor
      is identified. Usually it is a self-limited disorder, but corticosteroid therapy
      may be needed in life-threatening cases since early treatment with
      corticosteroids in severe cases can prevent complications. Oxacillin should be
      included among the drugs that can cause leucocytoclastic vasculitis.

PMID- 11337189
TI  - Activity of oral agents against pediatric isolates of Streptococcus pneumoniae.
AB  - An in vitro study of the activity of 10 oral agents against 153 pediatric
      isolates of Streptococcus pneumoniae identified moxifloxacin and levofloxacin as
      the most active agents regardless of penicillin or macrolide susceptibility.
      Moxifloxacin inhibited all strains at 0.25 microg/ml and was 8- to 16-fold more
      potent than levofloxacin.

PMID- 11337190
TI  - Trends in frequency and susceptibilities of Candida glabrata bloodstream isolates
      at a university hospital.
AB  - The frequency of isolation and antifungal susceptibility patterns to fluconazole
      and itraconazole were determined for 166 Candida glabrata isolates causing
      bloodstream infection at a single institution from 1995-2000. Findings
      demonstrated a trend of increasing resistance to itraconazole among the isolates,
      but no trend in resistance to fluconazole. The frequency of C. glabrata isolates
      among all blood culture isolates of Candida spp. causing bloodstream infection
      remained stable during the study period and ranged from 18-31%.

PMID- 11337191
TI  - Neuronal plasticity and degeneration.

PMID- 11337192
TI  - Disturbance of neuronal plasticity is a critical pathogenetic event in
      Alzheimer's disease.
AB  - Brain areas affected by AD pathology are primarily those structures that are
      invovled in the regulation of "higher brain functions". The functions these areas
      subserve such as learning, memory, perception, self-awareness, and consciousness
      require a life-long re-fittng of synaptic contacts that allows for the acquistion
      of new epigenetic information, a process based on a particularly high degree of
      structural plasticity. Here, we outline a hypothesis that it is the "labile state
      fo differentiation" of a subset of neurons in the adult brain that allows for
      ongoing neuroplastic processes after development is completed but at the same
      time renders these neurons particularly vulnerable. Mechanisms of molecular and
      cellular control of neuronal differentiation and proliferation might, thus, not
      only play a role during development but critically involved in the pathogenesis
      of neurodegeneration.

PMID- 11337193
TI  - Development of long-lasting potentiation effects in the dentate gyrus during
      pentylenetetrazol kindling.
AB  - In the present study kindling was induced in rats by repeated intraperitoneal
      injection of pentylenetetrazol (PTZ) once every 48 h. The resulting seizure
      stages were registered after each PTZ application. The development of PTZ-induced
      kindling and the time course of possible potentiation effects in the dentate
      gyrus were examined. The efficacy of perforant pathway transmission to the
      granule cells was tested in every second kindling session by measuring the
      monosynaptic evoked field potentials recorded in the dentate gyrus following
      single test stimuli of the perforant pathway at different times after PTZ
      injection in freely moving animals. The data suggest that establishment of a PTZ
      kindling is associated with the development of long-lasting potentiation of the
      field potentials. After completion of kindling it was demonstrated that kindled
      rats also show a diminished learning performance. The relationship between the
      development of potentiation phenomena in hippocampal substructures and learning
      impairment is discussed.

PMID- 11337194
TI  - Early onset of glutamatergic and GABAergic synaptic activity in the visual layers
      of the rodent superior colliculus.
AB  - During postnatal development, the retinocollicular pathway undergoes activity
      dependent refinement, resulting in the precise retinotopic map seen in adults.
      Previous studies established that retinal efferents reach the mouse superior
      colliculus (SC) by embryonic day 16. Morphologically, synapses were found in the
      rat SC before birth. As part of an extended project aimed at understanding the
      development of synaptic transmission in the visual layers of the SC, we report
      here the presence of functionally active synapses immediately after birth.
      Circuit activity in mouse SC neurons was detected in horizontal slices of the
      visual layers using cell-attached voltage clamp. The spontaneous discharge of
      action potentials was abolished by glutamatergic blockers and facilitated by
      bicuculline, showing that circuit activity is based on synaptic transmission and
      that the action of gamma-aminobutyric acid is inhibitory. Using whole-cell
      voltage clamp, spontaneous glutamatergic postsynaptic currents as well as
      miniature GABAergic postsynaptic currents were recorded on postnatal day 1.
      Excitatory and inhibitory postsynaptic currents could also be evoked by
      electrical stimulation. Glutamatergic postsynaptic currents comprised both (S)
      alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and N-methyl-D-aspartate
      receptor-mediated components. The early function of glutamatergic and GABAergic
      synaptic transmission in the visual layers of SC suggests that SC neurons are
      able to process information originating from retinal axons immediately after
      birth.

PMID- 11337195
TI  - Deafferentation of the septo-hippocampal pathway in rats as a model of the
      metabolic events in Alzheimer's disease.
AB  - Changes in the metabolic activity within the brain of patients suffering from
      Alzheimer's disease (AD) were investigated and compared with biochemical
      alterations in the hippocampus induced by fimbria/fornix transection in the rat.
      The deafferentation of the hippocampus results in a degeneration of cholinergic
      septo-hippocampal terminals accompanied by a persistent decrease of choline
      acetyltransferase (ChAT) and acetylcholine esterase (AChE) activities similar to
      the cholinergic malfunction in AD. In the animal model the [3H]-cytochalasin B
      binding to the glucose transporters was elevated up to the day 7 after surgery as
      was the activity of the phosphofructokinase (PFK) on day 3. A reactive
      astrogliosis could be evidenced by the upregulation of glial fibrillary acidic
      protein (GFAP). An increase of the PFK activity was also found in AD being
      accompanied by enhanced level of GFAP as well. A higher concentration of mRNA for
      all three isoenzymes of PFK was shown by reverse transcription (RT)-real time
      polymerase chain reaction (PCR) amplification. However, the pattern of PFK
      isoenzyme proteins and mRNAs did neither change in diseased human nor in the
      lesioned rat brain. The activities of the mitochondrial enzymes pyruvate
      dehydrogenase complex (PDHC) and cytochrome c oxidase (CO) were diminished in the
      lesioned rat hippocampus on day 7 as well as in AD brain. Subcellular
      fractionation showed that the activity of these enzymes was affected in the
      synaptosomal as well as in the extrasynaptosomal mitochondria indicating a loss
      of neuronal input and also a vulnerability of intrinsic hippocampal neurons
      and/or non-neuronal cells. The recovery of the mitochondrial enzyme activity in
      the animal model at later post lesion intervals may be the result of compensatory
      responses of surviving cells or of sprouting of other non-affected inputs. It is
      concluded that common metabolic mechanisms may underlie the concurrent
      degenerative and repair processes in the denervated hippocampus and the diseased
      Alzheimer brain.

PMID- 11337196
TI  - Expression of fructose-1,6-bisphosphatase mRNA isoforms in normal and basal
      forebrain cholinergic lesioned rat brain.
AB  - Fructose-1,6-bisphosphatase is one of the key enzymes in the gluconeogenic
      pathway predominantly occurring in liver, kidney and muscle. In the brain,
      fructose-1,6-bisphosphatase has been suggested to be an astrocyte-specific enzyme
      but the functional importance of glyconeogenesis in the brain is still unclear.
      To further elucidate the cellular source of fructose-1,6-bisphosphatase in the
      brain, non-radioactive in situ hybridizations were performed using digoxigenin
      labeled RNA probes based on the sequence of recently cloned rat liver and muscle
      fructose-1,6-bisphosphatase cDNAs. In situ hybridization using a riboprobe for
      the liver isoform revealed a location of the hybridization signal mainly in
      neurons, while rat muscle fructose-1,6-bisphosphatase mRNA was detected in both
      neurons and astrocytes in the hippocampal formation and in layer I of the
      cerebral cortex.RT-PCR using RNA preparations of rat astrocytes, neurons, and
      adult whole brain demonstrated a localization of liver fructose-1,6
      bisphosphatase mRNA isoform in neurons but not in astrocytes. The muscle fructose
      1,6-bisphosphatase mRNA isoform could be detected by RT-PCR in total rat brain,
      astrocytic, and neuronal mRNA preparations. The isoforms of fructose-1,6
      bisphosphatase mRNA seemingly demonstrate a distinct cellular expression pattern
      in rat brain suggesting a role of glyconeogenesis in both neurons and glial
      cells.

PMID- 11337197
TI  - Ontogenetic changes in protein level of amyloid precursor protein (APP) in growth
      cones and synaptosomes from rat brain and prenatal expression pattern of APP mRNA
      isoforms in developing rat embryo.
AB  - To elucidate the functional role of the amyloid precursor protein (APP) during
      brain ontogeny, developmental changes of APP levels in growth cones and
      synaptosomes were studied from embryonic day 14 up to postnatal day (PD) 400
      using Western analysis. APP level in growth cones was low during prenatal stages
      of development, but demonstrating a continuous increase from PD 3 up to PD 10.
      Highest concentration of APP in synaptosomes was found between PD 7 and 10,
      followed by a considerable decrease up to PD 30 and persisting at this level up
      to PD 400. In situ hybridization to differentiate between APP695 mRNA, APP751
      mRNA and APP770 mRNA revealed distinct age-related expression pattern of various
      APP isoforms. During prenatal brain development APP695 mRNA is maximally
      expressed in brain structures, containing differentiating nerve cells. APP751 and
      APP770 mRNA isoforms are diffusely distributed in the embryo throughout the
      prenatal period examined and their expression is higher in peripheral organs such
      as skin, lung, liver and bones as compared to the brain. The increase of APP
      level during synaptogenesis suggests a functional role of APP in the processes of
      neurite outgrowth and cell targeting as well as in the maintenance of the
      functional integrity of synapses in the mature brain. The APP695 isoform seems to
      be the major form involved in embryonic brain maturation.

PMID- 11337198
TI  - Fucosylated glycans in the periventricular structures and the cerebrospinal fluid
      of the fetal rat forebrain. An autoradiographic and lectin binding histiotopic
      study.
AB  - Our autoradiographic 3H-fucose incorporation study of the brains of 20-day-old
      rat fetuses showed that the synthesis of fucosylated glycans is significantly
      higher in the ventricular germinative zone of the forebrain hemisphere than in
      the more superficial layers, including the cortical plate. Intense incorporation
      of 3H-fucose also occurred in the choroid plexus, both its epithelial and stromal
      component, in the primordial ependymal lining of the lateral ventricles, meninges
      and capillaries of the forebrain parenchyma. In the lateral ventricles, densely
      labeled microprecipitates of the cerebrospinal fluid (CSF) were occasionally
      observed. The histiotopic differences in 3H-fucose labeling were absent, or were
      much less expressed, in the autoradiograms prepared from unfixed cryostat
      sections containing mainly unincorporated isotope. This indicates that the blood
      mediated supply of 3H-fucose to the studied brain compartments was essentially
      equal and our incorporation data reflect actual differences in the rate of
      fucosylation within the forebrain hemispheres. The cytochemical lectin-binding
      assay, carried out with Ulex europaeus and Lotus tetragonolobus agglutinins,
      showed that regions with a higher rate of 3H-fucose incorporation were also
      richer in fucose-bearing glycoconjugates. The study revealed that the
      periventricular regions and the CSF of fetal rat forebrain form a fucosylated
      glycan-enriched complex, which represents a new chemoarchitectonic feature that
      may be of importance for maintaining the germinative properties of the
      ventricular neuroepithelium and the growth of the hemispheric ventricles.

PMID- 11337199
TI  - Changes in the immune system in depression and dementia: causal or co-incidental
      effects?
AB  - It is now widely accepted that psychological stress and psychiatric illness can
      compromise immune function. Furthermore the mechanisms whereby such changes occur
      are probably associated with the activities of the cytokines and other
      inflammatory mediators of the immune system which are known to initiate changes
      in behaviour. This review aims to summarise the experimental and clinical
      evidence that implicates the pro-inflammatory cytokines in the pathological
      changes seen in major depression and in Alzheimer's disease (AD). In major
      depression, evidence is provided to show that both activation (e.g., macrophage
      activity, acute phase proteins) and inhibition (e.g., natural killer cell
      activity) of the immune system occur. Many of the behavioural changes seen in
      depression are simulated by three pro-inflammatory cytokines (IL-1, IL-6 and TNF
      alpha), which may produce their impact on the brain by activating cyclooxygenase,
      nitric acid synthase and corticotrophin releasing factor. Effective
      antidepressant treatments largely attenuate the immune changes thereby raising
      the possibility that the normalisation of central biogenic amine function that
      are conventionally implicated in the cause of depression may be secondary to
      those of the pro-inflammatory cytokines. With respect to AD, while the cause(s)
      are unknown, there is both experimental and clinical evidence to suggest that
      inflammatory processes in the brain caused in particular by TNF-alpha together
      with the subsequent rise in free radicals, are instrumental in causing the
      pathological changes which underlie the disease. Evidence in favour of the
      inflammatory hypothesis is supported by the finding that nonsteroidal anti
      inflammatory drugs slow down the progression of the disease.Although, more
      research is needed into the inter-relationships between the various pro
      inflammatory cytokines and the behavioural changes invoked in major depression
      and AD, the immunological hypothesis has been important in stimulating new
      concepts regarding the causes of the pathological changes in these diseases and
      how effective drug treatments may attenuate them.

PMID- 11337200
TI  - Developmentally induced microencephalopathy in guinea pigs--embryonic glial cell
      activation marks selective neuronal death.
AB  - We have recently shown that in utero treatment of guinea pigs with the DNA
      methylating substance methylazoxymethanol acetate (MAM) on gestation day (GD) 24
      results in neocortical microencephalopathy, increased protein kinase C activity
      and altered processing of the amyloid precursor protein in neocortex of the
      offsprings. In order to identify the primary neuronal lesions produced by MAM
      treatment, we mapped the 5-bromo-2'-deoxyuridine (BrdU)-incorporation in dividing
      neurons on GD 24 and we followed the effects of MAM-treatment on GD 24 on
      embryonic immediate early gene expression and on glial cell activation. BrdU
      injected on GD 24 labeled many neurons of the ventricular zone and of the
      intermediate zone but only scattered neurons of the cortical plate. When time
      mated guinea pigs were injected intraperitoneally with MAM on GD 24, we observed
      the activation of microglial cells in the ventricular/intermediate zone and the
      appearence of astrocytes between the intermediate zone and the cortical plate, 48
      h after intoxification. The activation of glial cells was accompanied by the
      neuronal expression of c-Fos but not of c-Jun in the ventricular/intermediate
      zone. Based on our observations on BrdU-incorporation and on the morphological
      outcome of MAM treatment in the juvenile guinea pig, our data presented here
      indicate that selective neurodegeneration during development induces the
      activation of both phagocytotic microglial cells and of astrocytes which might
      trophically support damaged neurons surviving this lesion procedure.

PMID- 11337201
TI  - N-tert-butyl-alpha-phenylnitrone, a free radical scavenger with
      anticholinesterase activity does not improve the cognitive performance of
      scopolamine-challenged rats.
AB  - Reversible inhibitors of acetylcholinesterase improve spatial learning and memory
      in animal models of cognitive impairment. Here we investigate if the beneficial
      effects of free radical scavenger N-tert-butyl-alpha-phenylnitrone (PBN) on
      cognitive performance could be explained by its recently discovered
      anticholinesterase activity. Morris water maze experiment was performed to
      examine the effect of PBN on the impairment of spatial learning and memory
      induced by the antagonist of cholinergic muscarinic transmission scopolamine. In
      situ hybridization histochemistry experiment was performed to study its effects
      on the induction of immediate early gene expression (c-fos, c-jun) by dopamine D1
      receptor agonist SKF-82958 and on the augmentation of the SKF-82958-induced
      expression of these genes by scopolamine. In both experiments, the effects of PBN
      were compared to the effects of reversible anticholinesterase physostigmine. We
      found that physostigmine but not PBN significantly reversed the cognitive
      impairment in scopolamine-challenged rats, prevented the induction of c-fos and c
      jun mRNAs by SKF-82958 and attenuated the augmentation of the SKF-82958-induced
      expression of these genes by scopolamine. The present experiments did not reveal
      a significant in vivo anticholinesterase activity of PBN.

PMID- 11337202
TI  - Regulation of regional cerebral blood flow by cholinergic fibers originating in
      the basal forebrain.
AB  - The intracranial neural vasodilative system of cholinergic fibers projecting from
      the basal forebrain to the cortex was discovered by Biesold, Inanami, Sato and
      Sato (Biesold, D., Inanami, O., Sato, A., Sato, Y., 1989. Stimulation of the
      nucleus basalis of Meynert increases cerebral cortical blood flow in rats.
      Neurosci. Lett. 98, 39-44) using laser Doppler flowmetry in anesthetized rats.
      This cholinergic vasodilative system, which operates by increasing extracellular
      ACh release, relies upon activation of both muscarinic and nicotinic cholinergic
      receptors in the parenchyma of the cortex. Further, the involvement of nitric
      oxide in this cholinergic vasodilation, indicates the necessity to this system of
      neurons, which contain nitric oxide synthase. The increase in cortical blood flow
      elicited by this cholinergic vasodilative system is independent of systemic blood
      pressure and is not coupled to cortical metabolic rates. This cholinergic
      vasodilative system may be activated by somatic afferent stimulation. Most of the
      data presented here were obtained in anesthetized animals.

PMID- 11337203
TI  - Muscle activity-resistant acetylcholine receptor accumulation is induced in
      places of former motor endplates in ectopically innervated regenerating rat
      muscles.
AB  - Expression of acetylcholine receptors (AChRs) in the extrajunctional muscle
      regions, but not in the neuromuscular junctions, is repressed by propagated
      electric activity in muscle fibers. During regeneration, subsynaptic-like
      specializations accumulating AChRs are induced in new myotubes by agrin attached
      to the synaptic basal lamina at the places of former motor endplates even in the
      absence of innervation. We examined whether AChRs still accumulated at these
      places when the regenerating muscles were ectopically innervated and the former
      synaptic places became extrajunctional. Rat soleus muscles were injured by
      bupivacaine and ischemia to produce complete myofiber degeneration. The soleus
      muscle nerve was permanently severed and the muscle was ectopically innervated by
      the peroneal nerve a few millimeters away from the former junctional region.
      After 4 weeks of regeneration, the muscles contracted upon nerve stimulation,
      showed little atrophy and the cross-section areas of their fibers were completely
      above the range in non-innervated regenerating muscles, indicating successful
      innervation. Subsynaptic-like specializations in the former junctional region
      still accumulated AChRs (and acetylcholinesterase) although no motor nerve
      endings were observed in their vicinity and the cross-section area of their
      fibers clearly demonstrated that they were ectopically innervated. We conclude
      that the expression of AChRs at the places of the former neuromuscular junctions
      in the ectopically innervated regenerated soleus muscles is activity-independent.

PMID- 11337204
TI  - Immunofluorescence and immunoelectron microscopic evidence for differences in
      myelination of GABAergic and cholinergic septohippocampal fibres.
AB  - It is known that the rat septohippocampal projection is realised at least by
      GABAergic, parvalbumin containing and cholinergic fibres. The GABAergic component
      originates from fast-firing and fast-conducting neurons, whereas the cholinergic
      component represents the slow-firing, slow-conducting type. The present
      immunofluorescence and immunoelectron microscopic study shows that the vast
      majority of parvalbumin-immunoreactive, GABAergic axons are surrounded by
      enormously thick myelin sheaths, but choline acetyltransferase immunoreactive
      axons were rarely found to be myelinated. In addition, cholinergic fibres show
      considerably smaller diameters. Accordingly, our results are correlated with the
      well-known differences in conduction velocities between the GABAergic and
      cholinergic fibres of the septohippocampal pathway, which depend on myelination
      and axon calibre.

PMID- 11337205
TI  - The Blame-X syndrome: problems and lessons in nosology, spectrum, and etiology.
AB  - Symptoms of a functional somatic syndrome have been noted in individual persons
      and groups for more than a century. Often associated with war, the syndrome has
      received diverse names and many proposed but unproved etiologies, including
      exposure to trauma, stress, chronic infection, psychosomatic, chemical, or
      environmental causes. In recent years, when attributed to agent X, the syndrome
      could be called the Blame-X syndrome. The clinical, legal, and other problems
      associated with the syndrome are a reflection of nosologic difficulties in
      identifying and choosing titles for apparently "new" ailments. The difficulties
      arise from the complex overlap of symptoms, diseases, and laboratory
      abnormalities found with modern technology, and from the frequent abandonment of
      pathophysiologic demands for appropriate correlation of symptoms and objective
      abnormalities. An important principle in naming apparently new ailments is to
      avoid etiologic titles until the etiologic agent has been suitably demonstrated.
      A premature causal name can impair a patient's recovery from the syndrome, and
      impede research that might find the true cause.

PMID- 11337206
TI  - Sources of heterogeneity in the meta-analysis of observational studies: the
      example of SIDS and sleeping position.
AB  - The study objective was to provide an example of how risk estimates might vary
      across studies of observational design, even when a causal association is present
      and to explore the possible sources of such variation. A meta-analysis of studies
      on the association between prone sleeping position and sudden infant death
      syndrome (SIDS) is used to illustrate how risk estimates might vary across
      studies. Data used were reported case-control studies of the association between
      sleeping position and SIDS that were published between 1970 and 1994. If the
      pooled odds ratio had been relied on to assess the association between sleeping
      position and SIDS without an accompanying examination of the reasons for
      heterogeneity, important insights into the causal significance of the
      relationship may have been lost. In meta-analyses of observational studies it is
      important to investigate the reasons for heterogeneity across studies.

PMID- 11337207
TI  - A comparative meta-analysis on the variability in test performance among FDA
      licensed enzyme immunosorbent assays for HIV antibody testing.
AB  - BACKGROUND: Although independently published studies have compared diagnostic
      test performance among various manufactured enzyme immunosorbent assays (EIAs)
      used in HIV antibody testing, none have attempted to formally synthesize such
      results through a comparative meta-analysis. In particular, no estimates of post
      FDA approval test performance, in terms of sensitivity and specificity, and their
      associated variability within each manufacturer, has been reported in the
      literature, along with an analysis of the relative differences in manufacturer
      test performance in practice (after FDA approval). METHODS: Retrieval of studies
      was done using several searching strategies, while retrieval of manufacturer
      information was done through package inserts and direct contacts. Comparisons of
      HIV antibody test performance across manufacturers and within a single
      manufacturer were made based on 16 estimates (from 11 articles) and 33 estimates
      (from 19 articles), respectively. A generalized linear model, based upon Bayes
      estimates of sensitivity and specificity, was used to assess the impact of
      several study-level covariates on the performance of these EIAs, with overall
      estimates of manufacturer test performance and associated variability obtained
      based on generalized estimating equations. RESULTS: Estimates of test performance
      were obtained across studies, with a significant (P < 0.01) difference between
      manufacturers. The test performance of each manufacturer significantly interacted
      (P < 0.05) with the following study-level covariates: type of population
      screened, year of diagnostic testing and study quality. Among a single
      manufacturer, Abbott, significant improvement in estimates of test sensitivity (P
      < 0.01) and specificity (P < 0.01) was observed with each newly produced antibody
      kit. CONCLUSION: Estimates on the relative differences in test performance within
      each manufacturer may be used for guiding decisions on the choice of EIA test kit
      for HIV antibodies, given the type of population screened, as well as cost and
      time considerations. In addition, the results of this meta-analysis may be used
      in modeling HIV prevalence when used as prior information within a Bayesian
      framework or for standardizing test results among various manufacturers.

PMID- 11337208
TI  - The homocysteine distribution: (mis)judging the burden.
AB  - The nonfasting plasma total homocysteine (P-tHcy) concentration was measured in a
      random sample of 3025 Dutch adults aged 20-65 years (main study). The positively
      skewed distribution had a geometric mean of 13.9 micromol/L in men and 12.6
      micromol/L in women. Blood of the main study was not cooled or centrifuged
      immediately after drawing. A stability study (n = 26) indicated that this could
      have resulted in a small (0.4 micromol/L) overestimation of the means. A
      comparative study (n = 88), and a reproduction of these results in an entirely
      different population (n = 213), showed a systematic difference in P-tHcy
      concentration of -2.4 micromol/L between our laboratory (Nijmegen, the
      Netherlands) and that in Bergen, Norway. With the information of the additional
      studies we provided precise and valid data of the Dutch P-tHcy distribution, from
      which we conclude the status in the Netherlands is worse than in other European
      countries. Furthermore, we showed that comparison of P-tHcy data is complicated
      unless the interlaboratory differences are known. @ 2001 Elsevier Science Inc.

PMID- 11337209
TI  - Hyperglycemia as a risk factor of mortality in a middle-aged Finnish population.
AB  - In 1990-1992, a population-based study was carried out in the city of Oulu in
      northern Finland, to assess the prevalence of diabetes mellitus (DM) and impaired
      glucose tolerance (IGT) in a middle-aged population. We report the mortality of
      the study population until 31 December 1998. Altogether 831 subjects (82%) (369
      men) participated in the baseline examinations, in which the prognostic risk
      factors were determined. Special attention was given to the effect of
      hyperglycemia on mortality. The WHO 1985, ADA 1997 and WHO 1999 criteria for
      diabetes, IGT and impaired fasting glucose (IFG) were used. Forty-one subjects
      (32 men) died during the average follow-up of 6.7 years, and the mortality rate
      was hence 7.7/1000 person-years. The results suggest that both fasting and post
      load hyperglycemia are important predictors of mortality. Estimated by the Cox
      proportional hazards regression, the unadjusted hazard ratio (HR) for death was
      2.5 (95% CI 0.9-6.6) in the subjects classified as diabetic according to the WHO
      1999 criteria compared to normoglycemic subjects. The corresponding HR of the
      subjects with IFG was 2.5 (95% CI 0.7-8.8) and that of the subjects with IGT 1.5
      (0.6-3.7). In addition, a high mortality was predicted by smoking (HR 4.2, 95% CI
      2.0-8.8), male gender (HR 3.5, 95% CI 1.6-7.9) and hypertension (HR 2.3, 95% CI
      1.1-5.1).

PMID- 11337210
TI  - Measuring health status using the Health Utilities Index: agreement between
      raters and between modalities of administration.
AB  - The aim of this study was to evaluate interrater and intermodality agreement in
      assessing health status using the Health Utilities Index. A random sample from a
      Dutch cohort of 14-year-old Very Low Birth Weight children and their parents were
      invited to participate in a face-to-face (n = 150) or telephone (n = 150)
      interview. All 300 participants were also sent a questionnaire by mail. Response
      rate was 68%. Interrater and intermodality agreement were high for the physical
      HUI3 attributes and poor for the psychological attributes. Children and parents
      reported more dysfunction in the psychological attributes when interviewed than
      when completing the mailed questionnaire. High agreement on the physical
      attributes may have resulted from the fact that hardly any dysfunction was
      reported in these attributes, and poor agreement in the psychological attributes
      may have been a result of the fact that in these attributes much more dysfunction
      was reported. In measuring children's health status using the HUI3, the results
      and their interpretation vary with the source of information and the modality of
      administration. For maximum comparability between studies, written self-report
      questionnaires seem the preferred option.

PMID- 11337211
TI  - Recall bias in a prospective cohort study of acute time-varying exposures:
      example from the herpetic eye disease study.
AB  - Recall bias is possible in a prospective cohort study when exposure status is
      transient and must be periodically recalled, and ascertainment occurs after
      symptom onset. We know of no published demonstration of such bias at play in a
      prospective cohort study. In a substudy of a randomized clinical trial, 308
      participants were prospectively followed to investigate potential acute triggers
      of ocular herpes simplex virus (HSV) recurrences. Participants reported on the
      presence of systemic infection or high psychological stress (exposures) on a home
      log that was completed weekly for up to 15 months and mailed to the study's
      coordinating centers. By protocol, exposure reporting was to occur on the last
      day of the week (Sunday) so that a prospective 1-week lag period between exposure
      and outcome in the following week could be assessed. The study outcome was
      development of a recurrence of ocular HSV disease documented by clinical
      examination. Using 35 weekly reports of exposure properly completed before the
      week of an outcome, there was no evidence of higher risk of HSV recurrence
      associated with systemic infection (rate ratio = 0.62, 95% confidence interval
      [CI]: 0.19-2.02) or high psychological stress rate (ratio = 0.0, 95% CI: 0.0
      undefined). In contrast, when the analysis was based on 26 weekly reports of
      exposure improperly completed on or after the date of outcome, the risk of
      recurrence associated with systemic infection was estimated to be 4-fold (rate
      ratio = 4.07, 95% CI: 1.84-8.98), and there was a suggestion of a 2-fold risk
      associated with high psychological stress (rate ratio = 2.02, 95% CI: 0.69-5.91).
      Without real-time monitoring of exposure reporting, preservation of the temporal
      exposure-disease relationship-an implicit assumption of the prospective cohort
      study design-may be particularly tenuous when transient exposures are
      investigated longitudinally.

PMID- 11337212
TI  - Intra-individual postural blood pressure variability and stroke in elderly
      nursing home residents.
AB  - Orthostatic hypotension (OH) is a potential risk factor for adverse
      cardiovascular events, but OH is highly variable and may not be detected on a
      single occasion. To assess the relation between intra-individual variability of
      systolic orthostatic blood pressure change (DeltaSBP) and cardiovascular
      outcomes, an algorithm was developed to identify DeltaSBP instability using
      repeated supine and standing BP measurements. A cohort of 673 nursing home
      residents underwent baseline postural BP measurements (supine to 1 minute of
      standing, four times in a single day) and were followed for up to 2 years. Two
      groups (stable vs. unstable) were identified based on an analysis of DeltaSBP
      variance components. Differences in outcomes were compared via Cox survival
      analysis. At baseline 12.6% were unstable, defined as a one standard deviation
      difference of at least 20.2 mmHg between DeltaSBP readings. Unstable subjects
      were more likely to have OH on at least one measurement (systolic BP drop of 20
      mmHg or more; 85% vs. 36%, respectively) and to be on psychotropic medication at
      baseline (47% vs 35%) (P-values <0.001). Other characteristics (including
      previous stroke) did not differ. During a mean follow-up of 10.3 months, stroke
      incidence was higher in unstable subjects (13.1% vs. 4.9%; P = 0.012), but
      ischemic heart disease and mortality rates were not significantly different
      (respectively, 13.5% vs. 7.4%, P = 0.115; 14.8% vs. 10.7%, P = 0.178). Survival
      analyses (adjusted for age, sex, psychotropic medications, body mass index,
      ischemic heart disease, and supine systolic pressure) confirmed a higher risk of
      stroke in unstable subjects (relative risk = 3.7, 95% CI: 1.6-8.4). Highly
      variable orthostatic BP measures may reflect impaired BP regulatory mechanisms in
      elders with occult cerebrovascular disease, or may directly affect cerebral blood
      flow. Orthostatic BP variability may be a better indicator of future stroke than
      a single supine or orthostatic change measure.

PMID- 11337213
TI  - Heart rate and mortality in a Japanese general population: an 18-year follow-up
      study.
AB  - The predictive power of elevated heart rate for total mortality was evaluated in
      a Japanese general population. A total of 573 male participants, aged 40 to 64,
      who underwent a health examination in 1977, were followed until 1994. Heart rate
      (beats per minute; bpm) was measured using an electrocardiogram. During the 18
      years, 82 subjects died; 18 from cerebro-cardiovascular diseases and 36 from
      cancer. In a multivariate proportional hazards regression model, age, elevated
      systolic and diastolic blood pressures, antihypertensive medication, heart rate,
      uric acid, vital capacity (inversely), and serum cholesterol (inversely) were
      significantly associated with all-cause death. Of these variables, elevated heart
      rate was the strongest predictor of all-cause death after adjustment for age.
      Resting heart rate levels were classified into five groups: < 60 (G1), 60-69
      (G2), 70-79 (G3), 80-89 (G4), and > or = 90 (G5) bpm. Heart rates of 60-69 (G2)
      bpm showed the lowest death rate (14.3%) and heart rate > or = 90 (G5) bpm showed
      the highest death rate (38.2%) after adjustments for age and other confounding
      factors. The relative risk of G2 versus G5 was 2.68. An increased mortality risk
      was shown in men whose heart rate was > or = 90 bpm. Moreover, a continuous model
      suggested a graded increase in risk, so that risk is likely elevated even for
      heart rates less than 90 bpm, and lowest risk may be around 60 bpm.

PMID- 11337214
TI  - Loss to follow-up in a longitudinal study on aging in Spain.
AB  - The objectives of this study were to describe follow-up dynamics in a
      longitudinal study on aging conducted in Spain between 1993 and 1997, and to
      identify the demographic, behavioral and health characteristics of persons who
      would later refuse to continue participating, move out of the area or be hard to
      locate (i.e., become lost to follow-up subjects). Data from the 1993 baseline
      survey were used to predict the probabilities of being lost to follow-up in the
      1995 and 1997 waves. Structural multiple logistic regressions were fitted and
      mean probabilities were estimated to identify patterns of loss to follow-up.
      After 4 years, 52% of baseline participants remained in the study, 24% had died,
      17% refused to continue participating, and 8.7% were impossible to locate. In the
      multivariate analysis, advanced age and living alone were independent predictors
      of loss to follow-up, and none of the health status variables remained
      significant. However, participation status in previous waves and the number of
      nonresponse items were strong independent predictors of further non
      participation. Our results suggest that an attitude against participation in
      surveys may be an independent predictor of losses to follow-up and efforts should
      be made to retain this subgroup of the population in the study. Further research
      on reasons why people are unwilling to participate in surveys and strategies to
      retain people in longitudinal studies is needed.

PMID- 11337215
TI  - Evaluating variations in medical practice between government primary care health
      centres.
AB  - We evaluated variations in medical care for diabetes among government health
      centres in Trinidad and Tobago. Data were analysed for 1579 subjects with
      clinical diabetes attending 23 health centres concerning 12 processes of care and
      six case-mix or outcome variables. Random effects models were used for analysis.
      Health centre level variation was appreciable. Intraclass correlations ranged
      from 0.025 to 0.316 for process of care variables and 0.000 to 0.056 for case-mix
      variables. Compared with health centres with only one nurse, patients attending
      those with three or more nurses received 1.18 (95% confidence interval 0.27 to
      2.09) more processes of care. Delivery of medical care varied among the health
      centres and those with higher staffing levels provided more processes of care.

PMID- 11337216
TI  - Evaluating adverse cardiovascular effects of drug treatment for benign prostatic
      hyperplasia (BPH): methodological considerations.
AB  - When studying the effects of drug exposure in diseases with a long asymptomatic
      clinical course, exposure classification may be biased by the gradually
      developing "visibility" of the disease. Benign prostatic hyperplasia (BPH) is
      such a disease. We found that cardiovascular morbidity is two times more
      prevalent in patients starting drug treatment for BPH when compared to age
      matched population controls. This resulted in a difference of cardiovascular
      prognostic factors between the exposed and non-exposed. This feature can
      jeopardize the validity of non-randomized comparisons of drug effects. Moreover,
      the existence of non-treatment strategies, disease under-reporting, and an
      elderly population with a high baseline risk of experiencing (cardiovascular)
      outcome events were encountered as methodological problems. When studying adverse
      cardiovascular effects in patients using BPH products in a non-randomized
      fashion, an important question is whether we can measure in the database all
      relevant prognostic factors and use the information for statistical adjustment.
      This question is an important challenge to observational research and once again
      stresses the need for control of possible biases in choosing an appropriate study
      design.

PMID- 11337217
TI  - Pharmacologic treatment of diabetes in long-term care.
AB  - The majority of patients with diabetes are elderly, but little is known about
      their disease management. This study evaluates the prevalence and correlates of
      treatment of elderly diabetics residing in long-term care. We performed a
      retrospective, cross-sectional study of 75,829 elderly diabetics residing in
      nursing homes from 1992 to 1996. Nearly half (47%) of the residents received no
      antidiabetic medications. Independent predictors not receiving antidiabetic
      medications included age, race, impaired physical ability, and impaired cognitive
      function. Although the absence of resident's blood glucose or glycosylated
      hemoglobin (HbA1c) values prevents us from passing judgment about the adequacy of
      diabetic care, further research is needed to understand why some residents do not
      receive antidiabetic medications in the long-term care setting.

PMID- 11337218
TI  - The association between antiulcer medication and initiation of cobalamin
      replacement in older persons.
AB  - As chronic use of antiulcer medications might predispose older persons to
      cobalamin deficiency, we studied participants (> 65 years) in the clinical
      examination of the Canadian Study of Health and Aging to test the association
      between the use of an antiulcer medication (histamine-2 blocker or proton pump
      inhibitor) at baseline with initiation of cobalamin replacement during the 5 year
      follow-up period. Of 1054 eligible subjects, 125 (11.7%) were taking an antiulcer
      medication at baseline. At follow-up, 49 (4.6%) had started cobalamin
      replacement. Antiulcer medication use at baseline was significantly associated
      with the initiation of cobalamin therapy (odds ratio 2.56, 95% confidence
      interval 1.30-5.05), even after adjusting for age, gender and institutional
      residence (odds ratio 2.61, 95% confidence interval 1.31-5.23). There is an
      independent association between the use of antiulcer medication and initiation of
      cobalamin therapy. While the relationship is not unambiguously causal, this
      finding underscores the need for judicious prescribing of antiulcer medications
      for older persons.

PMID- 11337219
TI  - Fat fetishism, dietary dread, and the freedom factor: an autobiographical
      memorandum.

PMID- 11337220
TI  - Airway biofilm disease.
AB  - This paper describes the formation of biofilm, its characteristics, its effect on
      the host cells and treatment of the condition. The airway biofilm diseases are
      known to be intractable and persistent; also, auto-immune factors play a role in
      the development of the symptoms. The characteristic of airway biofilm diseases is
      of a harmful auto-immune reaction occurring along with the symptoms which are
      different from the simple acute infection interaction between microorganism and
      host in an acute airway infection.

PMID- 11337221
TI  - Antibiotic selective pressure and development of bacterial resistance.
AB  - This study evaluates the development of resistance in Gram-negative rods to
      cefotaxime and ceftazidime, ofloxacin and ciprofloxacin, gentamicin and amikacin,
      meropenem and ampicillin/sulbactam over a five year period of use (1994-1998) at
      the University Hospital in Olomouc, Czech Republic. The development of bacterial
      resistance was linked with antibiotic use and hence selective pressure which was
      specific for the type of antibiotic and the bacterial species. Statistically
      significant correlations were found for the use of ofloxacin and resistance in
      Escherichia coli, Proteus vulgaris and Providencia rettgeri; cefotaxime and
      Enterobacter cloacae; ceftazidime and Acinetobacter spp., Enterobacter
      agglomerans and Proteus vulgaris; and gentamicin and Proteus mirabilis.

PMID- 11337222
TI  - Evaluation of two in vitro pharmacodynamic simulation models: microfiltration
      versus centrifugation-filtration.
AB  - Pharmacodynamic in vitro models that simulate serum antimicrobial concentrations
      provide more information about the activity of an antibiotic than MICs or
      traditional time-kill methods. The aim of this study was to compare two
      pharmacodynamic simulation models using ATCC strains of five different species
      and five antibiotics. In the first model (Centriprep-10 system), a filtration
      centrifugation process was used to eliminate the antibiotic; in the second model
      (microfiltration system) no centrifugation was necessary. The antibiotic
      concentrations tested were similar to those in serum after normal doses of
      cefuroxime, clarithromycin, ciprofloxacin, gentamicin and cefotaxime. No
      significant differences were observed in the killing rates between the models
      except in the case of Haemophilus influenzae and cefotaxime. The new
      microfiltration model had the following advantages: lack of the carry-over
      effect, the absence of centrifugation that could damage bacteria and the
      possibility of increasing the number of incubation periods to give a better fit
      of the kinetic profile of man.

PMID- 11337223
TI  - Performance of the VITEK2 system for identification and susceptibility testing of
      routine Enterobacteriaceae clinical isolates.
AB  - The VITEK2 system was evaluated with 138 fresh consecutive routine clinical
      Enterobacteriaceae isolates. Susceptibility results to 10 beta-lactams, three
      aminoglycosides and a quinolone were compared with those obtained following the
      NCCLS standard microdilution. API20E was used as reference method for
      identification. All but three isolates were correctly identified in 3 h at
      species level (97.8%), two isolates (1.4%) at genus level and only one isolate
      was misidentified. Overall essential agreement for susceptibility testing was
      97.1%. Discrepancies were mainly observed with piperacillin (1.1%), cefuroxime
      (0.6%) and amoxycillin/clavulanate (0.3%). Discrepancies for aminoglycosides and
      ciprofloxacin were low (<0.1%). Minor, major and very major errors (NCCLS
      categories) were 4.1%, 0.2% and 6.1%, respectively. Very major errors were due to
      piperacillin (4.5%), ampicillin (0.8%) and amoxycillin/clavulanate (0.8%). The
      VITEK2 system gave accurate identification and susceptibility testing results of
      routine Enterobacteriaceae clinical isolates.

PMID- 11337224
TI  - Activity of moxifloxacin and other quinolones against pneumococci resistant to
      first-line agents, or with high-level ciprofloxacin resistance.
AB  - The activity of moxifloxacin and other quinolones was assessed against 288
      epidemiologically diverse isolates of Streptococcus pneumoniae, many of them
      resistant to one or more first-line agents and/or with increased ciprofloxacin
      resistance (minimum inhibitory concentrations, MICs 16- > 64 mg/l compared with 1
      2 mg/l for most isolates). Moxifloxacin and grepafloxacin were the most active
      quinolone analogues, inhibiting about 90% of the isolates at < or = 1 mg/l,
      whereas levofloxacin inhibited 64% of isolates at < = 1 mg/l and ciprofloxacin
      inhibited 42%. Moxifloxacin also was the most active agent against isolates with
      elevated ciprofloxacin resistance (MIC 16- > 64 mg/l): moxifloxacin MICs of
      around 4 mg/l were seen for most such isolates, compared with 16-32 mg for
      levofloxacin and grepafloxacin. The activity of moxifloxacin against pneumococci
      resistant to one or more first-line agent suggests it will have a useful
      therapeutic role, although its activity against highly ciprofloxacin resistant
      isolates seems marginal.

PMID- 11337225
TI  - In vitro susceptibility to 15 antibiotics of vibrios isolated from penaeid
      shrimps in Northwestern Mexico.
AB  - The sensitivity of 144 isolates of Vibrio spp isolated from shrimp was compared
      using common antibiotics and those used in the shrimp industry. The in vitro
      susceptibility of the isolates was studied using amikacin, ampicillin,
      carbenicillin, cephalothin, cefotaxime, ceftriaxone, chloramphenicol, gentamicin,
      netilmicin, nitrofurantoin, pefloxacin, trimethoprim-sulphamethoxazole,
      enrofloxacin, oxytetracycline and florfenicol. The relationship between the
      minimum inhibitory concentration and the disk inhibition zone was also studied
      for some antibiotics.

PMID- 11337226
TI  - Contact imidazole activity against resistant bacteria and fungi.
AB  - The activities of miconazole and miconazole sulphosalicylate were evaluated by a
      contact test using strains of Enterococcus faecalis and Escherichia coli and
      Candida spp selected for their resistance. The results showed that killing of the
      organisms occurred within a few minutes. Imidazole activity required a medium of
      low electrical conductivity and a pH of 5.6. Greater sensitivity could be
      obtained with pretreatment of the microbial suspensions with sodium
      dioctylsulphosuccinate. Microorganisms tested in culture media with low
      electrical conductivity and at pH 5.6 showed enhanced sensitivity to azoles with
      MIC values about 20-30 times lower than those obtained using control media.
      Practical implications of the use of topical drugs are discussed.

PMID- 11337227
TI  - High prevalence of carriage of antibiotic-resistant Streptococcus pneumoniae in
      children in Kampala Uganda.
AB  - There are few data on antibiotic-resistant Streptococcus pneumoniae in Uganda. A
      total of 191 healthy children in Kampala, Uganda were screened for nasopharyngeal
      carriage of S. pneumoniae; 118 (62%) of the children were carriers. Antimicrobial
      susceptibility and serotype of 115 strains was determined. Ninety-six (83.5%) of
      the isolates were of intermediate resistance to penicillin and 19 (16.5%) were
      susceptible. All strains were susceptible to cefotaxime. The rates of resistance
      to other drugs were trimethoprim-sulphamethoxazole (83.5%), tetracycline (28.7%)
      and chloramphenicol (10.4%). All strains were susceptible to rifampicin,
      erythromycin and clindamycin. Serogroups 6, 9, 14, 19 and 23 accounted for 80% of
      the isolates. These data show that the rate of carriage of antibiotic-resistant
      pneumococci by children is high in Kampala, Uganda.

PMID- 11337228
TI  - Effect of different antibacterial agents and surfactant protein-A (SP-A) on
      adherence of some respiratory pathogens to bronchial epithelial cells.
AB  - Some antibiotics at sub-inhibitory concentrations are able to alter bacterial
      surface structures and modulate adhesiveness by affecting the expression of
      microbial adhesins. An important mechanism of pulmonary defence against pathogens
      is SP-A, one of the proteins of the alveolar surfactant having opsonizing
      activity. The aim of this study was to investigate the effect that sub-inhibitory
      concentrations of different antibiotics and physiological concentrations of SP-A
      (1 and 5 microg/ml) could exert on the adherence of respiratory pathogens to the
      bronchial epithelial cell line, WI26VA4. Cefdinir and clarithromycin showed high
      efficacy, mainly at 1/2 MIC, in reducing the adherence of Staphylococcus aureus,
      Streptococcus pneumoniae and Haemophilus influenzae strains to values lower or
      equal to 50% of the control; sparfloxacin showed the same effect on S. aureus and
      S. pneumoniae but teicoplanin only on S. pneumoniae. Other similar results were
      observed with netilmicin on Klebsiella pneumoniae (40%) and with cefepime and
      ciprofloxacin on Pseudomonas aeruginosa (60%). Clarithromycin reduced the
      adherence of K. pneumoniae to 80% although it is not active against this strain.
      Adherence of the test strains was not modified by SP-A alone or in combination
      with any of the antibiotics used.

PMID- 11337229
TI  - In vitro susceptibility of Vibrio spp. isolated from the environment.
AB  - Bacteria of the genus Vibrio include harmless aquatic strains as well as strains
      capable of causing epidemics of cholera and human intestinal diseases. Some of
      these species may show resistance to different antibiotics including cefotaxime,
      tetracycline and chloramphenicol. The susceptibility to different antibiotics was
      tested using 40 Vibrio alginolyticus, eight V. parahaemolyticus and six V.
      vulnificus strains isolated in the coastal waters of Northern Sardinia (Italy).
      The frequency of resistance to beta-lactams was unexpectedly high. More than 80%
      of Vibrio isolates were resistant to ampicillin and 2.5% of V. alginolyticus were
      resistant to ceftazidime and cefotetan. Forty percent of V. alginolyticus and
      three V. vulnificus isolates gave a positive nitrocefin test. PCR was also
      performed using selected primers chosen for having common sequences of bla(TEM)
      and bla(SHV) genes.

PMID- 11337230
TI  - Mupirocin resistance among Malaysian isolates of methicillin-resistant
      Staphylococcus aureus.
AB  - Four hundred methicillin-resistant Staphylococcus aureus strains (MRSA) from
      different geographical areas in Malaysia were tested for mupirocin susceptibility
      using minimum inhibitory concentration (MIC) determination. The majority of these
      strains (98.75%) were susceptible to mupirocin with MICs of < or = 4 mg/l. Fifty
      percent of these strains had MICs of 0.125 mg/l or less while 90% of the strains
      had MICs of 1 mg/l or less. Mupirocin resistance was detected in five strains
      (1.25%) and one of these (0.25%) had an MIC of 64 mg/l and the other four strains
      (1%), high-level resistance with MICs > 512 mg/l. Even though the rate of
      mupirocin resistance in MRSA is still low in Malaysia, its presence calls for a
      strict policy on mupirocin usage in Malaysian hospitals.

PMID- 11337231
TI  - Increasing resistance of M. tuberculosis to anti-TB drugs in Saudi Arabia.
AB  - The incidence of drug resistance in Mycobacterium tuberculosis (MTB) isolated
      from our hospital between April 1996 and March 1998 was compared with an earlier
      study (1993-1995). Thirty (29.7%) of 101 MTB isolates were resistant to one or
      more anti-TB drugs and 21 (20%) of 101 were multi-drug resistant M. tuberculosis
      (MDR-TB). Resistance was most common to isoniazid (28.7%), followed by
      streptomycin (22.8%) and rifampicin (20.8%). Resistance to pyrazinamide and
      ethambutol was 7.9 and 6.9%, respectively. There was a three-fold increase in
      resistance compared with the earlier study.

PMID- 11337232
TI  - Fungaemia in elderly patients.

PMID- 11337233
TI  - The antibacterial activity of Commelina erecta extracts.

PMID- 11337234
TI  - Eradication of Helicobacter pylori from the stomach and duodenum of patients with
      duodenal ulcers.

PMID- 11337235
TI  - Is there a place for intra-articular hyaluronate in osteoarthritis of the knee?
AB  - Viscosupplementation refers to the intra-articular injection of hyaluronic acid
      (HA) as a hyaluronate to relieve pain and improve function, usually in patients
      with knee OA. HA is the major constituent of a 1-2-micron layer on the surface of
      articular cartilage as well as a major constituent of synovial fluid (SF).
      Solutions of HA can act as lubricants when movements are slow and as shock
      absorbers when movements are fast. In arthritis, the molecular weight of HA is
      reduced, and so are its properties. Viscosupplementation has been advocated as a
      way of reversing this, but intra-articular HA has other properties, such as an
      anti-inflammatory effect, which may also contribute to any therapeutic effect.
      There is a large placebo effect from intra-articular injections, and the benefits
      of intra-articular glucocorticoids may be only slightly better than this effect.
      In only one randomised, placebo-controlled trial was the difference in response
      significant. Studies of intra-articular HA also show a marked placebo response
      (where it has been measured), but some have suggested a measurable benefit, which
      may be more prolonged that that of glucocorticoids. There is only a single study
      in which the effects of intra-articular therapy with placebo, glucocorticoids and
      viscosupplementation can be compared. Here, HA may have had a slightly longer
      period of benefit than triamcinolone hexacetonide or placebo. The very large
      placebo response after aspiration of the knee may seriously mislead those engaged
      in uncontrolled therapeutic evaluation of intra-articular therapy. Current
      evidence suggests that viscosupplements probably provide a similar level of pain
      relief to glucocorticoids and do so for several months, but the onset is slower,
      and there is the potential for local adverse reactions.

PMID- 11337236
TI  - Open wedge tibial osteotomy with acrylic bone cement as bone substitute.
AB  - We studied the results of 245 valgus producing high tibial osteotomies performed
      with the use of an opening wedge technique and rigid internal fixation followed
      by early passive and active motion of the knee. Previous studies have used iliac
      bone grafts or hemicollastasis held by an external fixator for opening the
      osteotomy. In our series the opening was obtained by a block of cement interposed
      in the postero-medial part of the osteotomy. This series confirms that the
      opening wedge osteotomy allows good accuracy for the correction. Ninety-three
      percent of the knees had a correction adjusted between 180 and 187 degrees for
      the hip-knee-ankle angle. Survivorship analysis showed an expected rate of
      survival, with conversion to a total knee on the end point, of 94% at 5 years,
      85% at 10 years and 68% at 15 years. Conversion to a total knee arthroplasty was
      accomplished without difficulty in the patients who had this procedure done. We
      recommend opening wedge tibial osteotomy with acrylic cement bone cement as bone
      substitute, rigid internal fixation, and early motion for patients who undergo
      high tibial osteotomy.

PMID- 11337237
TI  - External patellotibial transfixation: indications, operative technique and
      outcome.
AB  - Patellotibial transfixation with the MPT fixator is a new method of external
      stabilisation for lesions of the extensor mechanism of the knee joint. The
      biomechanical principle is the external transmission of tensile forces in the
      quadriceps muscle from the patella to the lower thigh and the translation of
      these forces into extension of the knee joint. The construction is an external
      patellotibial frame. In fitting method A, a Steinmann pin with central thread is
      inserted transversely through the patella and proximal tibia. Connection is made
      via laterally positioned rods with rotatable fixator jaws. In fitting method B, a
      Schanz screw is inserted sagittally into the proximal tibia and connected to the
      tibiocentral fixator jaw. In the frame construction a threaded pin is tightened
      into the fixator jaw. The MPT fixator is mostly used to secure suture repairs and
      transosseous refixations of the patellar ligament, or to reconstruct neglected
      patellar tendinous or osseous lesions of the distal extensor apparatus when
      functionally stable results cannot be obtained by osteosynthesis. The advantages
      of patellotibial transfixation are that: (1) a minimum of internal allogenic
      material is required to reconstruct the extensor apparatus and the repair is
      protected against excessive strain; (2) immediate functional post-operative
      therapy with an unlimited range of motion and early full weight-bearing is
      possible. Between 1990 and 1997 the MPT fixator was here used on 74 patients, 51
      of whom had an acute lesion of the extensor mechanism, 19 lesions had either been
      neglected or subjected to an earlier operation. Among 20 of the acutely injured
      knee joints there were other serious associated injuries. Fitting method A was
      used in 48 patients and fitting method B in 26 patients. In four patients the
      operation was followed by severe infection, owing to the fixator in two cases.
      The remaining 70 patients wore the system for an average of 7.3 weeks. Eight
      patients with caudal comminuted fractures who had had segmental patellectomy and
      transosseous refixation of the patellar tendon and 15 patients who had had
      transosseous suture refixation of the patellar ligament after rupture at the
      lower pole or suture repair after intraligamentous rupture, were followed up
      isokinetically and radiologically with IKDC scoring for an average of 49.3 months
      after the operation. The outcome was classified as normal or close to normal in
      19 patients and as abnormal in four. Isokinetically only five of the 23 had a 10
      20% deficiency in the strength of the extensor muscles of the operated leg in
      comparison to the opposite side. External patellotibial transfixation with the
      MPT fixator produced good operative results in re-establishing the continuity of
      the distal extensor apparatus of the knee joint and is an effective alternative
      to patellotibial cerclage with wire or synthetic ligament.

PMID- 11337238
TI  - Medium term outcome of the LCS cementless posterior cruciate retaining total knee
      replacements. Follow up and survivorship study of 35 operated knees.
AB  - Mobile bearing knee replacement has been designed to provide an effective
      prosthetic tool for improving long-term survivorship. Although, its potential
      long-term superiority has not been proven, an alarming possibility of its early
      mechanical failure has been previously reported. In the present study on 27
      patients with 35 replaced knees due to osteoarthritis, 97.1% of a 5-year
      survivorship of LCS mobile bearing cementless total knee prosthesis is reported.
      This high survival rate, with a satisfactory functional outcome at middle term
      follow-up has been achieved by following an optimal technique of implantation.
      Therefore, in the middle term this mobile bearing design of total knee
      replacement is no less effective than the conventional fixed bearing designs.

PMID- 11337239
TI  - Review of the clinical results of arthroscopic meniscal repair.
AB  - A total of 62 arthroscopic meniscal repairs (60 knees in 59 patients) over a 5
      year period were evaluated retrospectively to assess outcome and to identify
      factors that might improve future clinical results. The overall success rate was
      66.1%. Early repair within 3 months of sustaining the tear gave better results
      (91%) than if carried out later (58%). Suture repair alone yielded better results
      (78%) than meniscal arrows or a T-fix device (56%). Healing rates of atraumatic
      meniscus tears were much lower than for traumatic tears (42 vs. 73%). The
      isolated atraumatic medial meniscal tear appeared to do particularly poorly (33%
      healing) and may be better treated by meniscectomy.

PMID- 11337240
TI  - The Ilizarov method for failed knee arthrodesis following septic TKR.
AB  - Knee arthrodesis is a well-recognized salvage procedure in patients with infected
      total knee arthroplasties. If a fusion is achieved, it offers the opportunity for
      a stable lower limb and eradication of infection, but at the expense of knee
      motion. However, knee arthrodesis in this setting may be difficult to achieve
      because of poor bone stock, persistent infection, soft tissue compromise, and
      often the poor general health of the patient. We report two cases of failed knee
      arthrodesis following periprosthetic infection where a fusion was successfully
      achieved with open debridement and a hybrid advanced Ilizarov fixator.

PMID- 11337241
TI  - A straightforward method of assessing the accuracy of implantation of knee
      prostheses.
AB  - Accurate component placement in knee replacement surgery is important. The
      precision with which the implants are placed directly affects patient outcome as
      implant position and alignment influence stability, durability and patellar
      tracking. The ability to measure the accuracy of implantation of knee replacement
      components is valuable in assessing not only ones own technique but also in
      evaluating new instruments or implants and in teaching. The standard AP and
      lateral radiographs employed by most surgeons give inadequate information to
      assess alignment of each component accurately. We present a straightforward way
      of assessing femoral and tibial component alignment by using a series of three
      radiographs. This technique is reproducible and can be performed using standard
      equipment in any radiology department. This technique was applied to 160 total
      knee replacements performed using newly developed instrumentation. It was shown
      to be simple and the measurements were reproducible, with very little inter
      observer bias. We believe this technique has a role in audit, teaching, training
      and assessing new techniques and instruments.

PMID- 11337242
TI  - Comparison of EMG activity of medial and lateral hamstrings during isometric
      contractions at various cuff weight loads.
AB  - Since both the medial head (MH) and lateral head (LH) of the hamstring muscles
      contribute to knee flexion, this study investigated whether the relative
      electrical activity of these heads remained constant with respect to each other
      or changed during isometric contractions at five different resistance levels. The
      relative electrical activity of these two heads was determined by comparing their
      integrated EMG (iEMG). Forty-two volunteers with no history of right lower
      extremity injury or disease, between the ages of 18 and 35, were studied.
      Following motor point location, surface electrodes were placed over the MH and
      LH. Subjects, positioned prone, flexed the knee to 45 degrees using a sawhorse as
      a tactile cue to help maintain this position. Three recordings, 8 s in length,
      were taken at each subject's maximum isometric contraction and then using cuff
      weights of 1, 3, 5, and 7% of their body weight. The average of the three
      recordings was used in the analysis. During maximum isometric contraction (at 45
      degrees of knee flexion), the LH contributes a significantly greater percent of
      the total iEMG (63.4%) than the MH (P < 0.0001). Furthermore, within the four
      submaximal levels tested, the LH's contribution was significantly greater than
      the MH (P < 0.01). During submaximal isometric contractions, the LH percent
      contribution to total iEMG was less than its contribution during maximal
      isometric contraction, all P values < 0.005. As a result, during these same
      submaximal isometric contractions, the MH contribution to total iEMG was greater
      than its contribution during maximal isometric contraction, all P values <
      0.005).

PMID- 11337243
TI  - Failure strengths of suture vs. biodegradable arrow and staple for meniscal
      repair: an in vitro study.
AB  - A study was performed to determine the in vitro biomechanical behaviour of two
      'all inside' meniscal repair techniques (Meniscal Arrow [Bionx Implants Inc.] and
      Meniscal Staple [Surgical Dynamics Inc.]) and compare these directly with both a
      horizontal and vertical suture repair. Using 30 fresh bovine medial menisci,
      vertical 'bucket handle' tears were created 4 mm from the meniscus periphery.
      Repairs were subsequently performed, using four techniques, with 15 repairs in
      each group, a horizontally placed 3-metric Ethibond suture, a vertically placed 3
      metric Ethibond suture, a single 13-mm arrow and a single 7-mm staple. A tensile
      test was performed to determine the force at failure for each technique. The mean
      force at failure of the horizontal and vertical suture groups was 63.2 and 73.9
      N, respectively, 44.3 N for the arrow group and 17.8 N for the staple group. The
      mean forces at failure were significantly different (P < 0.005). The mean tensile
      strength of the meniscal staple was significantly lower than that of both suture
      and arrow groups. The 7-mm staple design may not allow adequate interdigitation
      between the barbed legs and the semicircular collagen fibres of the meniscus.

PMID- 11337244
TI  - Meniscal tearing and rheumatoid arthritis.
AB  - We report five cases of meniscal tears in patients who were subsequently found to
      have rheumatoid arthritis (RA) and discuss the management priorities with regard
      to symptom relief.

PMID- 11337245
TI  - Infected total knee replacement following a dental procedure in a severe
      haemophiliac.
AB  - This article documents the late infection of a total knee replacement in a
      haemophiliac following a dental procedure. It underlines the need for
      reconsideration of the current British guidelines regarding antibiotic
      prophylaxis for dental procedures in patients with total joint replacement.

PMID- 11337246
TI  - Growth arrest lines and recurrent patellar dislocation: a new sign.
AB  - The phenomenon of growth arrest lines has been widely described in the medical
      literature. They are usually found at the metaphysis of growing long bones and
      are the result of short periods of partial growth arrest. Recurrent dislocation
      of the patella is a well-recognised problem, particularly in adolescents. Several
      radiological features have been reported in association with patellar dislocation
      or instability. We have reported a hitherto undescribed radiological sign of
      patellar growth arrest lines on the skyline radiographs of two patients with this
      condition. The shape of the patella when symptoms were at their worst
      corresponded remarkably closely to the outline of the subsequent growth arrest
      line. We postulated that repeated dislocations adversely affect the process of
      normal maturation of the patella. With the resolution of symptoms, patella
      ossification resumes, leaving the telltale sign of previous injury in the form of
      a growth arrest line and an improvement in bone density once the patella has been
      stabilised and tracks normally.

PMID- 11337247
TI  - The immune system of invertebrates and vertebrates.

PMID- 11337248
TI  - Phylogeny of ion channels: clues to structure and function.
AB  - Voltage-gated ion channels are responsible for the electrical activity in a
      variety of cell types in modern-day animals. However, they represent the result
      of many millions of years of evolution of a family of ion channel proteins that
      are also found in prokaryotes and diverse eukaryotes, and probably exist in all
      life forms. This review traces the evolution of ion channels, with particular
      emphasis on the factors and evolutionary pathways that may have given rise to
      voltage-gated potassium (K+), calcium (Ca2+), and sodium (Na+) channels. The
      review also highlights the utility of comparing phylogenetically distinct
      versions of the same protein as a means to better understand the structure and
      function of proteins.

PMID- 11337249
TI  - Comparative enzymology, biochemistry and pathophysiology of human exo-alpha
      sialidases (neuraminidases).
AB  - This review summarizes the current research on human exo-alpha-sialidase
      (sialidase, neuraminidase). Where appropriate, the properties of viral,
      bacterial, and human sialidases have been compared. Sialic acids are implicated
      in diverse physiological processes. Sialidases, as enzymes acting upon sialic
      acids, assume importance as well. Sialidases hydrolyze the terminal, non
      reducing, sialic acid linkage in glycoproteins, glycolipids, gangliosides,
      polysaccharides, and synthetic molecules. Therefore, a variety of assays are
      available to measure sialidase activity. Human sialidase is present in several
      organs and cells. Its cellular distribution could be cytosolic, lysosomal, or in
      the membrane. Human sialidase occurs in a high molecular-mass complex with
      several other proteins, including cathepsin A and beta-galactosidase. Multi
      protein complexation is important for the in vivo integrity and catalytic
      activity of the sialidase. However, multi-protein complexation, the occurrence of
      isoenzymes, diverse subcellular localization, thermal instability, and membrane
      association have all contributed to difficulties in purifying and characterizing
      human sialidases. Human sialidase isoenzymes have recently been cloned and
      sequenced. Even though crystal structures for the human sialidases are not
      available, the highly conserved regions of the sialidase from various organisms
      have facilitated molecular modeling of the human enzyme and raise interesting
      evolutionary questions. While the molecular mechanisms vary, genetic defects
      leading to human sialidase deficiency are closely associated with at least two
      well-known human diseases, namely sialidosis and galactosialidosis. No therapy is
      currently available for either disease. A thorough investigation of human
      sialidases is therefore crucial to human health.

PMID- 11337250
TI  - The structure of Mordacia mordax insulin supports the monophyly of the
      Petromyzontiformes and an ancient divergence of Mordaciidae and Geotriidae.
AB  - The phylogenetic relationships between the two southern hemisphere lamprey
      families (Geotriidae and Mordaciidae) and their northern hemisphere counterparts
      (Petromyzontidae) are unresolved. Insulin was isolated from an extract of islet
      containing intestinal tissue from ammocoetes of the Australian lamprey, Mordacia
      mordax. Its primary structure was established as A-chain:
      GIVEQCCHRK10CSIYDMENYC20N and B-chain: SALMGTGGTH10LCGSHLVEAL20YVVCGQRGFF30
      YTP[SKG]. Although the residues in parentheses are only tentatively assigned,
      mass spectrometry supports the proposed sequence and demonstrates that Mordacia
      proinsulin, unlike proinsulin from Geotria australis, is fully processed to
      mature insulin. Insulins from M. mordax and G. australis and from the northern
      hemisphere lampreys Petromyzon marinus and Lampetra fluviatilis share a
      pentapeptide extension to N-terminus of the B-chain (Ser-Ala-Leu-Xaa-Gly) that
      has never been found in the insulins of any other vertebrate class. This
      observation provides support for the claim that the Petromyzontiformes constitute
      a monophyletic group. M. mordax insulin differs from that of G. australis by 18
      amino acid residues but by only four residues from the common sequence of P.
      marinus and L. fluviatilis insulin. These data are consistent with the view that
      Geotriidae and Mordaciidae have been separated for a long period and suggest that
      G. australis insulin has undergone an accelerated rate of molecular evolution.

PMID- 11337251
TI  - The redfish species Sebastes viviparus, Sebastes marinus and Sebastes mentella
      have different composition of their tissue fatty acids.
AB  - The fatty acid profile in the tissue of heart, gill, skull- and otolith-oil of
      the three redfish species, Sebastes viviparus, S. marinus and S. mentella was
      determined by a chemometric method, consisting of methanolysis of samples of the
      tissues and of the oils and gas chromatography of the resulting fatty acid methyl
      esters. The analytical data were treated by multivariate statistics comprising
      principal component analysis (PCA) and soft independent modeling of class analogy
      (SIMCA). Although the differences in fatty acid composition among the two tissues
      and two oils were the dominating features of the data, the three species had
      significantly different fatty acid profiles within each tissue. Variation among
      the individuals was considerable. The fatty acid profiles appeared to be species
      specific. The mutual relationship between S. marinus and S. mentella is closer
      than the relationship between either of them and S. viviparus. A comparison with
      a corresponding investigation on the same three species from another location
      indicates that the observed differences do not seem to be affected by biotic or
      abiotic factors.

PMID- 11337252
TI  - Cloning and characterization of porcine insulin gene.
AB  - The complete porcine preproinsulin cDNA and 1022 bp of its 5'-flanking region
      have been cloned by PCR-based technology and characterized. The porcine insulin
      gene has the same structure of three exons and two introns as that found in all
      insulin genes sequenced to date. Northern blot analysis of isolated adult porcine
      islets demonstrated an increase in steady-state insulin mRNA levels in response
      to high concentrations of glucose. Highly conserved cis-acting elements were
      found in the 5'-flanking region of the porcine insulin gene including multiple E
      and A elements as well as a cAMP responsive element (CRE). Tissue-specific
      activity of the proximal promoter was confirmed by transient transfection of the
      promoter/reporter gene constructs. This information now makes it possible for
      regulation and expression of the porcine insulin gene to be analyzed.

PMID- 11337253
TI  - cDNA sequence and gene expression of storage protein-2--a juvenile hormone
      suppressible hexamerin from the fall webworm, Hyphantria cunea Drury.
AB  - We isolated and sequenced a cDNA clone corresponding to storage protein-2 (SP-2)
      from the fall webworm, Hyphantria cunea. The cDNA for SP-2 (2572 bp) codes for a
      747-residue protein with a predicted molecular mass of 88.5 kDa. The calculated
      isoelectric point is 7.6. Multiple alignment analysis of amino acid sequence
      revealed that SP-2 is most similar to BJHSP2 (74.3% identity). According to both
      the phylogenetic analyses and criteria for amino acid composition, SP-2 belongs
      to the subfamily of moderately methionine-rich storage proteins (3.2% methionine,
      11.8% aromatic amino acid). Topical application of the JH analog, methoprene,
      after head ligation of larvae, suppressed transcription of the SP-2 gene,
      indicating hormonal effects at the transcriptional level. The SP-2 transcript was
      detected by Northern blot analysis in Malpighian tubules, in addition to the fat
      body where it was most abundant. The local expression of SP-2 in Malpighian
      tubules suggests that it may have some function in that organ.

PMID- 11337254
TI  - Oxyconformity in the intertidal worm Sipunculus nudus: the mitochondrial
      background and energetic consequences.
AB  - The energetic consequences of strict oxyconformity in the intertidal worm S.
      nudus were studied by characterizing the Po2 dependence of respiration in
      mitochondria isolated from the body wall tissue. Mitochondrial respiration rose
      in a Po2 range between 2.8 and 31.3 kPa from a mean of 56.5 to 223.9 nmol O mg
      protein(-1) h(-1). Respiration was sensitive to both salicylhydroxamic acid
      (SHAM) and KCN. Po2 dependence remained unchanged with saturating and non
      saturating substrate levels (malate, glutamate and ADP). A concomitant decrease
      of the ATP/O ratio revealed a lower ATP yield of aerobic metabolism at elevated
      Po2. Obviously, oxyconforming respiration implies progressive uncoupling of
      mitochondria. The decrease in ATP/O ratios at higher Po2 was completely
      reversible. Addition of 90.9 micromol H2O2 l(-1) did not inhibit ATP synthesis.
      Both observations suggest that oxidative injury did not contribute to
      oxyconformity. The contribution of the rates of mitochondrial ROS production and
      proton leakiness to mitochondrial oxygen consumption and uncoupling was
      investigated by using oligomycin as a specific inhibitor of the ATP synthase. The
      maximum contribution of oligomycin independent respiration to state 3 respiration
      remained below 6% and showed a minor, insignificant increase at elevated Po2, at
      a slope significantly lower than the increment of state 3 respiration. Therefore,
      Po2 dependent mitochondrial proton leakage or ROS production cannot explain
      oxyconformity. In conclusion Po2 dependent state 3 respiration likely relates to
      the progressive contribution of an alternative oxidase (cytochrome o), which is
      characterized by a low affinity to oxygen and an ATP/O ratio similar to the
      branched respiratory system of bacteria. The molecular nature of the alternative
      oxidase in lower invertebrates is still obscure.

PMID- 11337255
TI  - Purification and characterization of a putative vitellogenin from the ovary of
      amphioxus (Branchiostoma belcheri tsingtaunese).
AB  - An oocyte-yolk protein was purified by double-step chromatography from amphioxus
      ovaries. The purified protein appeared to exist as a homodimer of approximately
      320 kDa in native polyacrylamide gel electrophoresis (PAGE), and was reduced to a
      single monomer of approximately 160 kDa in sodium dodecyl sulfate-PAGE (SDS
      PAGE). The protein was characterized as a phospholipoglycoprotein by native PAGE
      and staining of gels for phosphorus with methyl green, for lipids with oil red O
      and Sudan black B, and for carbohydrates using periodic acid/Schiff reagent. In
      addition, the amino acid composition of the oocyte-yolk protein was generally
      similar to that of vitellogenins (Vgs) isolated from different phyla of animals
      including both vertebrates and invertebrates. The purified
      phospholipoglycoprotein is thus considered as putative amphioxus Vg.

PMID- 11337256
TI  - Sulfide oxidation coupled to ATP synthesis in chicken liver mitochondria.
AB  - Chicken liver mitochondria consumed O2 at an accelerated rate when supplied with
      low concentrations of hydrogen sulfide. Maximum respiration occurred in 10 microM
      sulfide, and continued more slowly up to concentrations as high as 60 microM.
      Sulfide oxidation was coupled to adenosine triphosphate (ATP) synthesis, as shown
      by firefly luciferase luminescence and by measurement of the mitochondrial
      membrane electrochemical gradient. Synthesis of ATP required low, steady-state
      concentrations of sulfide (< 5 microM), which were maintained by use of a syringe
      pump. The ratio of consumed O2 to sulfide changed at low sulfide and O2
      concentrations, indicating alternative metabolic reactions and products. In low
      concentrations of sulfide, presumably most similar to physiological, the
      O2/sulfide ratio was 0.75. This is the first report of sulfide oxidation linked
      to ATP synthesis in any organism not specifically adapted to a sulfide-rich
      environment. We suggest that this may be a widespread mitochondrial trait, and
      that it is consistent with the hypothesis that mitochondria originated from
      sulfide-oxidizing symbionts.

PMID- 11337257
TI  - Protein requirements in larvae and adults of Scaptotrigona postica (Hymenoptera:
      Apidae [correction of Apidia], Meliponinae): midgut proteolytic activity and
      pollen digestion.
AB  - The number and degree of digestion of pollen grains in the midgut and rectum, the
      midgut proteolytic activity and the time of pollen grain passage through the
      digestive tract in the stingless bee Scaptotrigona postica (Latreille) have been
      analyzed. The results show similar protein requirements among larvae, nurse bees
      and queens, as well as between forager bees and old males, but these requirements
      are higher in individuals from the former groups than in those from the latter.
      Although protein requirements have been demonstrated to vary according to a bee's
      activity in the colony, they are similar among bees from different castes or
      sexes. These changes in feeding behavior are related to the bee's function and to
      less competition for nourishment among individuals of the colony. It is also
      noted that pollen grains took between 6 and 28 h to pass through the digestive
      tract. Pollen grains are irregularly accumulated in the various regions of the
      midgut, which may reflect functional differentiation throughout the midgut.

PMID- 11337258
TI  - Regulation of glycosylation-dependent cell adhesion molecule 1 (GlyCAM-1) gene in
      the mouse mammary gland differs from that of casein genes.
AB  - Mouse glycosylation-dependent cell adhesion molecule 1 (GlyCAM-1), also known as
      mC26 and homologous to bovine PP3, is a milk protein synthesized in the mammary
      gland. Several studies have investigated the regulation of casein, the major milk
      protein, gene in the mammary gland, but little is known about GlyCAM-1. Here we
      examined GlyCAM-1 gene expression in mouse mammary epithelial cells. First, we
      detected GlyCAM-1 expression in mammary epithelial cells in situ by
      immunohistochemistry; almost all mammary epithelial cells of the lactating mouse
      expressed GlyCAM-1. Second, mammary epithelial cells were digested with
      collagenase and cultured with insulin, prolactin and/or glucocorticoid. alpha
      Casein and beta-casein genes were expressed following treatment with insulin,
      prolactin and glucocorticoid. In contrast, GlyCAM-1 expression could not be
      detected with any combination of these three hormones. We also analyzed changes
      in the levels of GlyCAM-1 and caseins mRNAs in cultured cells. The addition of
      hormones to the culture medium increased casein mRNAs, but surprisingly reduced
      GlyCAM-1 mRNA. Our results suggest that the mechanisms that regulate GlyCAM-1
      gene in mammary cells of lactating mice are different from those involved in the
      regulation of casein genes.

PMID- 11337259
TI  - Effect of carnosine administration on metabolic parameters in bilharzia-infected
      hamsters.
AB  - Carnosine is a naturally occurring dipeptide (beta-alanyl-L-histidine) found in
      muscles, brain and other tissues. This study was designed to test the ability of
      carnosine to offset metabolic disturbances induced by Schistosoma mansoni
      parasitism. Results indicate that parasitic infection caused elevation of liver
      weight/body weight in S. mansoni-infected hamsters, induced lipid peroxidation
      and reduced glycogen levels. Moreover, adenylate energy charge (AEC) and ATP/ADP
      and ATP/AMP concentration ratios were markedly lower in infected hamsters.
      Administration of carnosine (10 mg/day) for 15 days concurrent with infection
      effectively reduced worm burden and egg count. Administration of carnosine 2 and
      4 weeks post-exposure only partially ameliorated the S. mansoni effects on
      metabolism. Carnosine treatment also normalized most of the parameters measured,
      including glycogen repletion, the antioxidant status and AEC. These finding
      support the use of carnosine for possible intervention in schistosomiasis.

PMID- 11337260
TI  - Glutathione S-transferases of Aulacorthum solani and Acyrthosiphon pisum: partial
      purification and characterization.
AB  - Glutathione S-transferases (GST) play an important role in the detoxification of
      many substances including allelochemicals from plants. Brassicaceae plants
      contain glucosinolates and emit volatile isothiocyanates which affect the GST
      system. A comparison of the GST of two aphid species, the generalist Aulacorthum
      solani found on Brassicaceae and the Fabaceae specialist Acyrthosiphon pisum, was
      made to try to explain their respective feeding behaviour. Differences of GST
      were determined among the two aphid species based on purification by affinity
      chromatography, SDS-PAGE and on kinetic studies. Purification yields using an
      epoxy-activated Sepharose 6B column were highly different for the two aphid
      species (18% and 34% for A. solani and A. pisum, respectively). These variations
      were confirmed by SDS-PAGE. While only a 27-kDa band was observed for A. pisum,
      two bands of approximately 25-kDa were visualized for the generalist aphid, A.
      solani. Considering the kinetic results, differences of Km and Vmax were observed
      following the aphid species when a range of substrates (CDNB and DCNB) and GSH
      concentrations were tested. Studies on the detoxification enzymes of generalist
      and specialist herbivores would be undertaken to determine accurately the effect
      of the host plant on the organisms eating them, particularly in terms of
      biochemical and ecological advantages.

PMID- 11337261
TI  - Lipids of brush border membrane vesicles (BBMV) from Plutella xylostella
      resistant and susceptible to Cry1Ac delta-endotoxin of Bacillus thuringiensis.
AB  - Plutella xylostella (PX) that were 130000-fold more resistant to Cry1Ac were
      selected from the susceptible strain and maintained in the laboratory. The LC50
      of the susceptible strain (PXS) was 0.38 microg toxin/g diet, whereas that of the
      resistant strain (PXR) was 4800 microg toxin/g diet. Brush border membrane
      vesicles (BBMV) were prepared from both PXS and PXR. In ligand blot analysis,
      Cry1Ac bound to a 120-kDa protein of BBMV; however, the intensity of the band was
      almost equal in both strains of insect. Hence, we analyzed the lipid components
      of BBMV from PXS and PXR. BBMV lipids were fractionated into non-polar lipid,
      phospholipid, neutral glycolipid and acidic glycolipid. Neutral glycolipid
      content was substantially lower in the BBMV of PXR than of PXS. The same trend
      was observed when lipids were extracted from whole midgut instead of BBMV. Thin
      layer chromatography of midgut neutral glycolipids revealed the presence of more
      than seven components. Among the midgut neutral glycolipids, a possible
      hexasaccharylceramide and a possible trisaccharylceramide of PXR were less than
      half the level found in PXS. The other lipid fractions in PXR and PXS were
      similar to each other.

PMID- 11337262
TI  - Spawning and season affect lipid content and fatty acid composition of ovary and
      liver in Japanese catfish (Silurus asotus).
AB  - The influences of spawning and season on lipid content, lipid classes, and fatty
      acid composition were assessed in ovary and liver of wild and cultured Japanese
      catfish (Silurus asotus). The lipid content (7.3+/-1.6 g/100 g wet wt.) of ovary
      from wild catfish at spawning was higher than that at post-spawn. However, no
      influence of spawning on the lipid content of liver was observed. Docosahexaenoic
      acid [DHA, C22:6(n-3)] in ovary lipids was 12.3+/-0.5% of total fatty acids. The
      percentage of n-7 monounsaturated fatty acids in triacylglycerol from the ovary
      and liver in the spawning season was high. Percentages of C22:6(n-3) in
      phosphatidylcholine and phosphatidylethanolamine from ovary were higher during
      spawning than after spawning. No significant differences were observed in the
      lipid content of ovary and liver from cultured catfish between seasons (summer
      vs. winter). Content of arachidonic acid (C20:4n-6) in ovary and liver from
      cultured catfish was higher in summer than in winter. There were differences in
      lipid classes of ovary and liver by spawning and season. These results suggest
      that the lipid metabolism in Japanese catfish is greatly influenced by spawning
      and season.

PMID- 11337263
TI  - Differential expression of the fibroin gene in developmental stages of silkworm,
      Antheraea mylitta (Saturniidae).
AB  - Fibroin gene expression during the larval developmental stages of the Saturniid
      silkworm, Antheraea mylitta, was analyzed. Northern blot analysis of larval silk
      gland total RNA using the fibroin gene as a probe showed that fibroin is
      expressed in the intermoult stages and repressed during the moulting stages.
      Abundance of fibroin transcripts gradually increased from the third to fifth
      intermoult stage, reaching a peak in the fifth intermoult. Transcripts declined
      during the early spinning stage. Western blot analysis of fibroin protein
      production with anti-fibroin antibody confirmed the differential fibroin
      expression, in accordance with fibroin mRNA synthesis. Dot blot hybridization of
      genomic DNA isolated from each larval developmental stage with the labelled
      fibroin gene showed that at the genomic level, the relative concentration of the
      fibroin gene was constant throughout the developmental stages. Our data confirm
      that fibroin gene expression in A. mylitta, like in B. mori, is transcriptionally
      controlled and shows differential temporal variations.

PMID- 11337264
TI  - Telomerase and oral cancer.
AB  - The development of malignant neoplasms is a multistep process and it is believed
      that multiple genetic alterations are involved. The progression of neoplastic
      lesions is also characterized by reactivation of telomerase, a ribonucleoprotein
      complex enzyme that adds telomere repeats at the ends of chromosomes. In view of
      the close association between telomerase and malignancy, this molecule may prove
      to be a useful marker for malignancy. This review focuses on the diagnostic and
      therapeutic potential of telomerase. The experimental data for telomerase assays
      with the potential for oral cancer detection and diagnosis are also reviewed.

PMID- 11337265
TI  - Selective deletion of p14(ARF) exon 1beta of the INK4a locus in oral squamous
      cell carcinomas of Indians.
AB  - The tumor suppressor gene - p16 INK4/CDKN2/MTS1 and its alternate splice product
      p14 (ARF), constitute the INK4a locus. We have examined the integrity of exon
      1beta of p14(ARF) gene of oral squamous cell carcinomas (n=58) in untreated
      Indian patients. No mutations were detected in this region by PCR-SSCP analysis
      of the tumor DNA's. Further, PCR-based analysis revealed homozygous deletions of
      exon 1beta in 14 of the 58 tumors; these results were confirmed by hybridization
      of tumor DNAs with exon 1beta specific probe. The deletions were limited to the
      exon 1beta while the exons coding p16/INK4 were not affected. Except in two cases
      these deletions were mutually exclusive to the p53 inactivating mutations. These
      observations suggest an alternate mechanism of loss of p14(ARF) in the genesis of
      oral squamous cell carcinomas.

PMID- 11337266
TI  - Trends and spatial distribution of oral cancer mortality in Sao Paulo, Brazil,
      1980-1998.
AB  - We assessed oral cancer mortality data in Sao Paulo to study trends of the
      disease and its distribution by areas of the city. We standardized death rates by
      gender and age group, and also supplied complementary information regarding oral
      cancer incidence. Oral cancer mortality remained stationary at high levels during
      the study period. Site-specific death rates revealed high figures for two
      categories of site: tongue and unspecified parts of mouth. Gum cancer death rates
      -the most easily diagnosed site-specific oral cancer at a routine dental
      examination--fell sharply, possibly as a consequence of the recent expansion in
      community dental health services in the city. In spite of this observation, the
      increase of death rates related to unspecified parts of the mouth points to the
      deficiencies of health services in detecting most of oral cancer cases early.
      Spatial data analysis enabled indication of areas and socio-economic factors
      associated with poorer profile in oral cancer mortality, important information
      for the targeting of health resources directed to the screening, prevention and
      education in oral cancer.

PMID- 11337267
TI  - Homozygous deletions on the short arm of chromosome 3 in human oral squamous cell
      carcinomas.
AB  - Recent cytogenetic and allelic deletion analyses have demonstrated that deletions
      on the short arm of chromosome 3 (3p) are frequently found in various cancers,
      including oral squamous cell carcinomas (OSCCs). This suggests that one or more
      tumor suppressor gene(s) for these malignancies might be located on 3p. In the
      present study, to further define the region(s) on 3p that harbor putative tumor
      suppressor gene(s) for OSCCs, we have investigated the existence of homozygous
      deletions (HDs) at 34 loci on 3p, in 14 OSCC cell lines. HDs were detected within
      the FRA3B region at 3p14.2 in only two cell lines (HSC-4 and TSU). Recently, the
      human fragile histidine triad (FHIT) gene was isolated from this region,
      abnormalities of which have been found at high frequencies in several types of
      human cancers. We also examined the expression of the FHIT gene, using reverse
      transcription-polymerase chain reaction (RT-PCR) and exon-specific PCR, in the
      two OSCC cell lines which showed HDs at 3p14.2. There was no detectable
      expression of exon 5, which was the first protein-coding exon of FHIT gene, in
      HSC-4 cells, indicating that this region was homozygously deleted in this cell
      line. On the other hand, HD in the TSU cells did not affect the coding region of
      the FHIT gene, and the wild-type transcript was detected by RT-PCR. Therefore,
      several candidate tumor suppressor genes, including the FHIT gene, may reside in
      these homozygously deleted regions. To our knowledge, this is the first report of
      HDs on 3p in OSCCs.

PMID- 11337268
TI  - Vascular invasion in squamous cell carcinomas of human oral mucosa.
AB  - The process of vascular invasion of human oral squamous cell carcinomas was
      histologically and immunohistochemically studied in surgical and autopsy
      specimens. Hematoxylin-eosin, Masson's trichrome, and immunohistochemical
      stainings for Ulex europaeus I lectin binding, CD31, and type IV collagen were
      done to differentiate lymphatic and blood vessels and to demonstrate basement
      membranes in vascular walls and around carcinoma cell nests was observed. With
      growth of tumor, there was mechanical disruption of vascular walls and
      endothelial cells by carcinoma cell nests. After disrupting vascular walls, they
      invaded into the lumen as clusters, not as single cells. At the blood vessel
      invasion sites, inflammatory reactions were seen around carcinoma cell nests
      inside as well as outside lumina with microthrombotic reactions due to
      endothelial injury. At the lymphatic invasion sites, carcinoma cell nests
      maintained their volume inside the lumen and the cells adhered tightly to each
      other, and inflammatory reaction was scarcely seen. These findings showed that
      mechanical pressure has an important role in the vascular invasion of human oral
      squamous cell carcinoma.

PMID- 11337269
TI  - Immunohistochemical aspects of basal cell adenoma and canalicular adenoma of
      salivary glands.
AB  - Basal cell adenoma is a benign epithelial neoplasm with a uniform histologic
      appearance dominated by basaloid cells. Those cells may be distributed in various
      arrangements as solid, trabecular, tubular and membranous. Canalicular adenoma is
      also a benign neoplasm composed by columnar cells arranged in branching and
      interconnecting cords of single or double cell thick rows. There is some
      disagreement among investigators about whether canalicular adenoma should be
      included within the basal cell adenoma histologic spectrum. In the present study
      we compared the expression of cytokeratins (CK), vimentin and muscle-specific
      actin, utilizing immunohistochemical technique, in three cases diagnosed as basal
      cell adenomas predominantly of the solid type, and three cases of canalicular
      adenomas. The results obtained showed a distinct immunoprofile for both
      neoplasms. Solid areas of basal cell adenomas did not stain for any of the tested
      antibodies; only when there was tubular differentiation, those structures
      expressed CKs 7, 8, 14, and 19 in luminal cells and vimentin in non-luminal
      cells. On the other hand, canalicular adenomas strongly expressed CKs 7 and 13.
      The panel of antibodies utilized supports the separation of the two entities.

PMID- 11337270
TI  - Angiostatin gene therapy inhibits the growth of murine squamous cell carcinoma in
      vivo.
AB  - Tumor growth is an angiogenesis-dependent process and therapeutic strategies
      aimed at inhibiting angiogenesis are theoretically attractive. Angiostatin has
      been shown to potently inhibit endothelial proliferation in vitro and tumor
      growth in vivo. We now show that a shift in the balance of tumor angiogenesis by
      gene transfer of a cDNA coding for mouse angiostatin into mouse squamous cell
      carcinoma NRS-1 and SCC-VII cells suppresses tumor growth in vivo. The inhibition
      of an angiostatin-transfected tumor was accompanied by a marked reduction in
      vascularity and the presence of many apoptotic tumor cells. However, transfected
      angiostatin cDNA does not affect the expression of the vascular endothelial
      growth factor (VEGF) and VEGF-R2 in the vascular endothelium. The inhibition
      mechanisms of neovascularization may be mediated independent of VEGF:VEGF-R2
      complex. Our data may provide a useful approach for human oral cancer therapy by
      gene therapy with angiostatin.

PMID- 11337271
TI  - Peplomycin-induced apoptosis in oral squamous carcinoma cells depends on
      bleomycin sensitivity.
AB  - Oral squamous carcinoma cell line SSCKN cells were shown to be highly sensitive
      to bleomycin, whereas SCCTF cells were minimally sensitive to this reagent. To
      determine whether the anticancer drug resistance to oral squamous carcinoma cells
      could be related to the degree of the drug-induced apoptosis, we examined the
      effects of peplomycin on induction of apoptosis in these cells. After reaching
      subconfluence, SCCKN and SCCTF cells were exposed to various concentrations of
      peplomycin. Peplomycin caused cytotoxicity in both SCCKN and SCCTF cells in a
      dose-dependent fashion with the maximal effect at concentrations of 1 and 10
      microM, respectively, as determined by phase-contrast microscopy and WST-1 cell
      viability assay. By using the Hoechst 33342 staining, we observed marked nuclear
      condensation and fragmentation of chromatin in SCCKN cells treated with 1 microM
      peplomycin. However, SCCTF cells treated with 1 microM peplomycin showed neither
      nuclear condensation nor fragmentation. DNA ladder formation was also detected in
      both cell lines by treatment with peplomycin. The induced DNA ladder formation in
      SCCKN and SCCTF cells was dose-dependent, with the maximal effect at
      concentrations of 5 and 50 microM, respectively. Bleomycin also induced DNA
      ladder formation in SCCKN and SCCTF cells with different sensitivities. Mitomycin
      C induced DNA laddering in both SCCKN and SCCTF cells; however, the intensity of
      DNA ladder formation was almost the same in both cell lines. The present results
      indicate that peplomycin-induced apoptosis in oral squamous carcinoma cell lines
      depends on the sensitivity of these cells to bleomycin.

PMID- 11337272
TI  - Establishment of an oral squamous cell carcinoma cell line (NOS-1) exhibiting
      amplification of the erbB-1 oncogene and point mutation of p53 tumor suppressor
      gene: its biological characteristics and animal model of local invasion by
      orthotopic transplantation of the cell line.
AB  - We established a new cancer cell line, NOS-1, which was derived from a human oral
      primary squamous cell carcinoma. Geneticin treatment was adopted to eliminate
      contaminating fibroblasts and to enrich tumor cells in the early stage of the
      culture. The NOS-1 cells showed epithelial morphological features with light and
      electron microscopy, and immunohistochemical analysis confirmed their epithelial
      origin. Overexpression of mutant p53 protein, a p53 point mutation at codon 248
      with transition from CGG to TGG, and amplification of the erbB-1
      oncogene/epidermal growth factor receptor gene were also observed in NOS-1 cells.
      The NOS-1 cells formed tumors in nude mice when transplanted subcutaneously into
      their backs. Further, they were transplantable orthotopically in the tongues of
      nude mice, and the transplanted tumors in the tongue showed diffuse invasion
      without forming capsules. The NOS-1 cells were useful for elucidating the
      mechanism involving p53 inactivation and erbB-1 oncogene amplification, as well
      as treatment of oral cancer.

PMID- 11337273
TI  - Metastasis of breast carcinoma to mandibular gingiva.
AB  - Metastatic tumours to the oral region are rare but more often involve the jaws
      rather than the oral soft tissues. In this report, an infiltrative ductal
      carcinoma of the breast that metastasised to the mandibular gingiva is presented.
      The patient consulted her dentist for what she thought was a dental abscess in
      the bicuspid region of the lower left jaw. However, her dentist referred her for
      a specialist opinion of the lesion. The patient's medical history revealed that
      she had undergone a breast 'lumpectomy' 1 year previously. A provisional
      diagnosis of primary or metastatic malignancy was made, and a biopsy was
      performed. Microscopically, the lesion showed features of a poorly differentiated
      infiltrative ductal carcinoma. Subsequent microscopic review of the primary
      lesion also showed a poorly differentiated infiltrating ductal carcinoma of the
      breast identical to the features observed in the metastatic lesion.

PMID- 11337274
TI  - Testicular embryonal carcinoma metastatic to the labial mucosa of the upper lip.
AB  - An unusual case of testicular embryonal carcinoma metastatic to the labial mucosa
      of the upper lip is reported. The clinical features and the management of the
      metastatic oral lesion are presented. In patients with known systemic malignancy,
      oral swellings may be an indication of a metastatic deposit.

PMID- 11337275
TI  - Co-expression of multiple transgenes in mouse CNS: a comparison of strategies.
AB  - The introduction of two transgenes into one animal is increasingly common as
      transgenic experiments become more sophisticated. In this study we examine two
      strategies for creating double transgenic founders from a single microinjection.
      In the first approach, two constructs, each with its own promoter element, were
      coinjected into the pronucleus. In the second approach, both transgenes were
      cloned into one vector, separated by an internal ribosomal entry site (IRES), and
      placed under control of a single promoter. Both strategies save time and increase
      the percentage of double transgenic offspring over the standard method of mating
      single transgenic lines. However, despite high transgene copy numbers, the
      bicistronic lines did not show robust expression of either protein. Copy number
      and protein expression correlated much better in the coinjected lines, with
      expression levels in one line approaching that observed in some of our best
      single transgenic controls. Thus we recommend coinjection of individual plasmids
      for the generation of multiply transgenic founders.

PMID- 11337276
TI  - Enzymatic synthesis of chiral intermediates for Omapatrilat, an antihypertensive
      drug.
AB  - Biocatalytic processes were used to prepare chiral intermediates required for the
      synthesis of Omapatrilat 1 by three different routes. The synthesis and enzymatic
      conversion of 2-keto-6-hydroxyhexanoic acid 3 to L-6-hydroxynorleucine 2 was
      demonstrated by reductive amination using beef liver glutamate dehydrogenase. To
      avoid the lengthy chemical synthesis of the ketoacid 3, a second route was
      developed to prepare the ketoacid by treatment of racemic 6-hydroxy norleucine
      [readily available from hydrolysis of 5-(4-hydroxybutyl) hydantoin 4] with D
      amino acid oxidase from porcine kidney or Trigonopsis variabilis followed by
      reductive amination to convert the mixture completely to L-6-hydroxynorleucine in
      98% yield and 99% enantiomeric excess (e.e.). The enzymatic synthesis of (S)-2
      amino-5-(1,3-dioxolan-2-yl)-pentanoic acid (allysine ethylene acetal, 5) was
      demonstrated using phenylalanine dehydrogenase (PDH) from T. intermedius.
      Phenylalanine dehydrogenase was cloned and overexpressed in Escherichia coli and
      Pichia pastoris. Using PDH from E. coli or P. pastoris, the enzymatic process was
      scale-up to prepare kg quantity of allysine ethylene acetal 5. The reaction
      yields of >94% and e.e. of >98% were obtained for allysine ethylene acetal 5. An
      enzymatic process was developed for the synthesis of [4S-(4a,7a,10ab)]1-octahydro
      5-oxo-4 [[(phenylmethoxy)carbonyl]amino]-7H-pyrido-[2,1-b] [1,3]thiazepine-7
      carboxylic acid [BMS-199541-01]. The enzymatic oxidation of the epsilon-amino
      group of lysine in the dipeptide dimer N(2)-[N[[(phenyl-methoxy)carbonyl] L
      homocysteinyl] L-lysine)-1,1-disulphide [BMS-201391-01] to produce BMS-199541-01
      using a novel L-lysine epsilon-aminotransferase (LAT) from Sphingomonas
      paucimobilis SC 16113 was demonstrated. This enzyme was overexpressed in E. coli
      and a process was developed using the recombinant enzyme.

PMID- 11337277
TI  - PNA oligomers as tools for specific modulation of gene expression.
AB  - Small synthetic molecules that can specifically inhibit translation and/or
      transcription have shown great promise as potential antisense/antigene drugs.
      Peptide nucleic acid (PNA), an oligonucleotide mimic, has a non-charged achiral
      polyamide backbone to which the nucleobases are attached. PNA oligomers are
      extremely stable in biological fluids and they specifically hybridise to DNA or
      RNA in a complementary manner, forming very strong heteroduplexes. Some of the
      mRNAs have yet undetermined and possibly long half-lives, successful down
      regulation of gene expression by antisense oligonucleotides (ON) requires that
      the antisense agent is long lived. PNA fulfils this requirement better than
      phosphodiester or phosphorothioate ONs. PNA can inhibit transcription and
      translation of respective genes by tight binding to DNA or mRNA. First in vitro
      experiments to specifically down regulate protein expression by PNA have been
      followed by successful antisense and antigene application of PNA oligomers in
      vivo. This review discusses the principles of the in vitro and in vivo use of PNA
      oligonucleotides.

PMID- 11337278
TI  - A new model for intermediate molecular weight recombinant bispecific and
      trispecific antibodies by efficient heterodimerization of single chain variable
      domains through fusion to a Fab-chain.
AB  - Due to their specificity and versatility in use, bispecific antibodies (BsAbs)
      are promising therapeutic tools in tomorrow's medicine, provided sufficient BsAb
      can be produced. Expression systems favoring efficient heterodimerization of
      intermediate-sized bispecific antibodies will significantly improve existing
      production methods. Recombinant BsAb can be made by fusing single chain variable
      fragments (scFv) to a heterodimerization domain. We compare the efficiency of the
      isolated CL and CH1 constant domains with complete Fab chains to drive
      heterodimerization of BsAbs in mammalian cells. We found that the isolated CL:CH1
      domain interaction was inefficient for secretion of heterodimers. However, when
      the complete Fab chains were used, secretion of a heterodimerized bispecific
      antibody was successful. Since the Fab chain encodes a binding specificity on its
      own, bispecific (BsAb) or trispecific (TsAb) antibodies can be made by C-terminal
      fusion of scFv molecules to the L or Fd Fab chains. This gave rise to disulphide
      stabilized Fab-scFv BsAb (Bibody)or Fab-(scFv)2 TsAb (Tribody) of intermediate
      molecular size. Heterodimerization of the L and Fd-containing fusion proteins was
      very efficient, and up to 90% of all secreted antibody fragments was in the
      desired heterodimerized format. All building blocks remained functional in the
      fusion product, and the bispecific character of the molecules as well as the
      immunological functionality was demonstrated.

PMID- 11337279
TI  - Biomarkers for transitional cell carcinoma-pro.

PMID- 11337280
TI  - Biomarkers for transitional cell carcinoma-con.

PMID- 11337281
TI  - P53 in bladder cancer: mechanism of action, prognostic value, and target for
      therapy.

PMID- 11337282
TI  - RB activation and repression of C-MYC transcription precede apoptosis of human
      prostate epithelial cells.
AB  - OBJECTIVES: The retinoblastoma gene (Rb) encodes a transcriptional regulatory
      protein that functions in the regulation of cellular growth, differentiation, and
      survival. Many of the target genes of Rb with respect to growth regulation and
      differentiation have been identified. However, the identities of the Rb target
      genes involved in the regulation of cell survival and cell death (apoptosis) are
      unknown. We sought to determine whether the c-myc oncogene, a known target of Rb
      activity in cell cycle control, is also recruited in an apoptotic pathway
      uniquely regulated by Rb in prostate epithelial cells. METHODS: We previously
      described a cell culture model to study the apoptosis of prostate cancer cells in
      which the human prostate cancer line, LNCaP, will undergo apoptosis after
      inducible expression and activation of the alpha isozyme of protein kinase C
      (PKC) or after exposure to low concentrations of the PKC activator TPA. Rb
      protein and c-myc mRNA and protein were evaluated in the Rb+/+ LNCaP and in the
      Rb-/- DU145 prostate cancer cells. RESULTS: TPA-induced apoptosis in LNCaP cells
      was preceded by the rapid depletion of c-myc mRNA. The DU145 cultures were
      resistant to TPA-induced apoptosis and the c-myc mRNA levels remained elevated.
      The examination of Rb protein in the LNCaP cells revealed rapid dephosphorylation
      preceding both c-myc protein depletion and apoptosis. Additionally, pretreatment
      of LNCaP cells with staurosporine, a potent inhibitor of several isozymes of the
      PKC family, inhibited apoptosis in these cells and completely blocked activation
      of Rb and repression of c-myc. CONCLUSIONS: On the basis of these studies, we
      suggest that induction of PKC-mediated apoptosis of Rb+/+ prostate cancer cells
      occurs by means of an intracellular pathway that involves the activation of Rb
      and repression of c-myc transcription.

PMID- 11337283
TI  - How do urology residents manage personal finances?
AB  - OBJECTIVES: To examine personal financial management among residents to answer
      three research questions: do residents make reasonable financial choices; why do
      some residents not save; and what steps can be taken to improve residents'
      personal financial decisions. METHODS: Portions of the Federal Reserve Board's
      Survey of Consumer Finances were modified and piloted to elicit demographic,
      expense, saving, and income data. The final questionnaire was completed by 151
      urology residents at 20 programs. RESULTS: Comparing residents with the general
      population in the same age and income categories, the median debt/household
      income ratio was 2.38 versus 0.64. Residents had greater educational debt,
      greater noneducational debt, and lower savings. Resident participation in
      retirement accounts was 100% at institutions with employer-matching 401k or 403b
      plans, 63% at institutions with nonmatching 401k or 403b plans, and 48% at
      institutions without retirement plans for residents (P = 0.002). Fifty-nine
      percent of residents budgeted expenses, 27% had cash balances below $1000, 51%
      had paid interest charges on credit cards within the previous year, and 12%
      maintained unpaid credit card balances greater than $10,000. The median resident
      income was $38,400. CONCLUSIONS: A significant minority of residents appear not
      to make reasonable financial choices. Some residents save little because of a
      failure to budget, indebtedness, high projected income growth, or insufficient
      attention to personal financial management. Residents save more when they are
      eligible for tax-deferred retirement plans, particularly when their institution
      matches their contributions. Many residents would benefit from instruction
      concerning prudent financial management.

PMID- 11337284
TI  - Efficacy of chemotherapy for prostatic tuberculosis-a clinical and histologic
      follow-up study.
AB  - OBJECTIVES: To characterize the clinical features of prostatic tuberculosis and
      to evaluate the short and long-term results of antituberculous chemotherapy.
      METHODS: Eighteen patients (mean age 66.7 +/- 10.2 years) with prostatic
      tuberculosis were included in this study. The median pretreatment prostate
      specific antigen (PSA) level was 2.7 ng/mL (range 0.3 to 31). The PSA level was
      greater than 4.0 ng/mL in 6 patients (33.3%). Eight patients (44.4%) received a
      triple-drug regimen of rifampin, ethambutol, and isoniazid for more than 6
      months. The mean duration of chemotherapy was 7.6 months (range 6 to 12). Of the
      8 patients, 3 underwent chemotherapy longer because of concurrent tuberculosis of
      other organs. Follow-up studies included digital rectal examination, total PSA
      determination, and transrectal prostate biopsy. RESULTS: Ten patients were
      eligible for regular follow-up. All the patients were symptom free during follow
      up. The median length of follow-up was 3.4 years (range 1 to 9). The average
      number of follow-up transrectal prostate biopsies was 2.4 (range 2 to 3). The
      follow-up histologic findings showed nodular hyperplasia in 7 patients and
      chronic inflammatory cell infiltration in 3 patients. No acid-fast bacillus was
      found in any follow-up specimen. Similarly, subsequent transrectal biopsy showed
      no relapse after a median length of 3.4 years of follow-up. Of the 6 patients
      with elevated PSA levels, the post-treatment PSA returned to normal in 3
      patients. CONCLUSIONS: Our results suggest that a triple-drug regimen of 6
      months' duration can successfully control prostatic tuberculosis. Histologic
      follow-up is a good method for monitoring the efficacy of treatment. Transrectal
      prostate biopsy is an important tool for the diagnosis and follow-up of prostatic
      tuberculosis.

PMID- 11337286
TI  - Incidence and outcome of patients with adrenal metastases of renal cell cancer.
AB  - OBJECTIVES: To evaluate the outcome of patients with adrenal metastasis in renal
      tumors to establish the oncologic necessity of adrenalectomy in these patients.
      Radical nephrectomy for renal cell cancer includes simultaneous ipsilateral
      adrenalectomy. Recent reports suggest that adrenal involvement in renal cell
      cancer is rare and can be predicted by computed tomography or distinct
      algorithms. METHODS: In a retrospective analysis of 866 consecutive patients who
      underwent nephrectomy and adrenalectomy, we established the rate of adrenal
      metastasis and obtained follow-up information to evaluate disease outcome.
      RESULTS: We calculated an adrenal metastasis rate of 3.1% (n = 27); of these 27
      patients, only 6 (0.7% of all patients) presented with a solitary adrenal
      metastasis. Kaplan-Meier analysis demonstrated that patients with solitary
      adrenal and multiple metastases have a poor outcome. The median survival of
      patients with localized renal cancer was 43.9 months compared with 21.3 months
      for patients with a solitary adrenal metastasis and 11.0 months for patients with
      multiple metastases. CONCLUSIONS: Ipsilateral, solitary, and synchronous
      metastases in renal cell cancer are rare and patients have a poor outcome despite
      surgical resection. Therefore, simultaneous adrenalectomy can be omitted during
      radical nephrectomy if the preoperative examinations or algorithms used do not
      predict adrenal metastasis in the patient with renal cell cancer.

PMID- 11337287
TI  - Tolerability of bacille Calmette-Guerin maintenance therapy for superficial
      bladder cancer.
AB  - OBJECTIVES: To study the influence of adverse reactions on adherence to an
      immunotherapy maintenance schedule and the recurrence rate of bladder cancer.
      Bacille Calmette-Guerin immunotherapy has documented efficacy in the management
      of high-risk superficial bladder cancer. However, the optimal duration of
      intravesical bacille Calmette-Guerin therapy and the risk/benefit ratio of
      maintenance therapy are controversial. METHODS: From April 1996 to April 2000, 72
      patients with superficial bladder cancer were treated with Immucyst (six
      consecutive weekly instillations of 81 mg) and then received maintenance therapy
      consisting of three consecutive weekly instillations 3, 6, 12, 18, 24, 30, and 36
      months later. Adverse reactions, studied during 518 instillations, were
      classified in four categories using a scale based on the World Health
      Organization recommendations, and their impact on the adherence to therapy was
      analyzed. RESULTS: After an average follow-up of 24 months, a durable disease
      free response was observed in 84.9% of the patients; 12.5% of patients had a
      relapse and 2.6% had disease progression. The response rate was similar in
      patients with and without adverse reactions. Only 14 patients (19%) received all
      the scheduled maintenance instillations. The dose was reduced in 41 patients
      (57%), and treatment was stopped in 28 patients (39%). In multivariate analysis,
      an adverse event score of 1.5 or greater during induction therapy was
      significantly associated with cessation or modification of maintenance therapy (P
      = 0.01). CONCLUSIONS: The scale developed in this study to monitor the adverse
      reactions to bacille Calmette-Guerin and their impact on the adherence to
      maintenance therapy may be helpful for tailoring maintenance regimens or
      implementing protective measures (dose reduction or treatment postponement).

PMID- 11337288
TI  - A new diagnostic algorithm for the evaluation of microscopic hematuria.
AB  - OBJECTIVES: To evaluate a new diagnostic algorithm for microscopic hematuria in
      which intravenous urography (IVU) is performed as a secondary radiographic study
      when microhematuria has persisted for 3 months after the initial workup with
      renal ultrasound (US) and cystoscopy was negative. METHODS: We evaluated 372
      consecutive patients who presented with microhematuria and negative urine
      cultures and cytologic findings at our institution. All patients underwent renal
      US scanning and cystoscopy as their initial evaluation. All patients underwent re
      evaluation 3 months after the initial workup. Patients with persistent
      microhematuria with no apparent etiology were then evaluated with IVU. RESULTS:
      The initial evaluation was negative in 212 of 372 patients. Eighty-one of these
      patients had persistence of their microhematuria at the 3-month follow-up without
      a definitive diagnosis. Seventy-five of these patients underwent IVU.
      Abnormalities were found in 11 of the 75 patients. Six patients had renal stones,
      two had ureteral stones, two had ureteral tumors, and one had a tumor of the
      renal pelvis. Forty of the 131 patients with resolution of their microhematuria
      underwent IVU at their request. All those studies were normal. CONCLUSIONS: The
      combination of cystoscopy and renal US along with urinalysis, urine culture, and
      cytology is a good initial evaluation in patients with microhematuria. Those
      patients with persistent microhematuria after 3 months without definite etiology
      of the bleeding may still benefit from IVU.

PMID- 11337289
TI  - Does angiogenesis predict recurrence in superficial transitional cell carcinoma
      of the bladder?
AB  - OBJECTIVES: To investigate the role of angiogenesis in predicting tumor
      recurrence and its correlation with established clinicopathologic prognostic
      factors in superficial transitional cell carcinoma of the bladder. METHODS: The
      paraffin sections of 80 superficial papillary transitional cell bladder carcinoma
      specimens were stained with CD31 antibody to label the vascular endothelium using
      the standard streptavidin-biotin-immunoperoxidase method. The vascular surface
      density (VSD) equivalent to the vascular surface area per unit of tissue volume
      and number of vessels per square millimeter of stroma (NVES) were assessed by
      means of stereology, and these morphometric parameters of angiogenesis were
      statistically analyzed to interpret the relation to tumor recurrence in addition
      to tumor stage, grade, size, and number and the presence of carcinoma in situ.
      RESULTS: VSD and NVES values showed no statistically significant difference
      between pTa and pT1 tumors or patients with and without recurrence. In contrast,
      VSD and NVES values were found to increase in higher grade tumors (P = 0.019).
      VSD values were also higher in patients with coexisting carcinoma in situ in pTa
      tumors (P <0.001). Tumor number and size and recurrence number and time to the
      first recurrence did not correlate with any vascular parameters. CONCLUSIONS:
      Stereologic assessment of angiogenesis does not help to predict recurrence in
      superficial bladder cancer. Angiogenic parameters appeared to be well correlated
      with the conventional histologic grading system. Otherwise, the present study did
      not show any correlation of angiogenesis with any potential prognostic factors.
      This may be due to the diverse angiogenic pathways occurring in invasive and
      superficial tumors.

PMID- 11337290
TI  - Do bacteriostatic urethral lubricants affect the clinical efficacy of
      intravesical bacillus Calmette-Guerin therapy?
AB  - OBJECTIVES: To investigate the effect of a bacteriostatic urethral lubricant on
      the clinical efficacy of intravesical bacillus Calmette-Guerin (BCG) therapy.
      METHODS: Between July 1987 and August 1999, 389 patients with superficial
      urothelial carcinoma of the bladder (pTa [multilocular, size greater than 2 cm,
      recurrent tumor], pT1, pTis) were treated adjuvantly with BCG in a 6-week
      intravesical cycle after complete transurethral tumor resection of the bladder.
      Within the framework of a prospective study on recurrence and progression of
      superficial urothelial carcinoma of the bladder after transurethral resection and
      BCG therapy, we retrospectively studied the clinical value of the observation
      that the use of bacteriostatic urethral lubricants reduces the viability and thus
      the efficacy of BCG. If a lubricant induces a clinically relevant reduction in
      the viability of BCG, instillation without lubricant should lead to a lower rate
      of recurrence and possibly a lower rate of progression. Lubricant (11 mL) was
      used during catheterization in every male patient in our population (group 1, n =
      317, 81.5%); no lubricant was used in the women serving as the control group
      (group 2, n = 72, 18.5%). The two groups were similar with respect to age,
      distribution of tumor stage and grade, multifocality, and frequency of previous
      bladder carcinoma (Levene test, P = 0.008). The median follow-up was 54 months
      (range 4 to 143). RESULTS: Of the 389 patients, 90 (23.1%) developed recurrence
      during the follow-up period: 73 (23%) in group 1 and 17 (23.6%) in group 2 (P
      value not significant). Progression occurred in 14 patients in group 1 (4.4%) and
      in 8 patients in group 2 (11%) (P = 0.043). In groups 1 and 2, 19.2% and 47.1%,
      respectively, of the recurrences were progressive (P = 0.026). CONCLUSIONS: The
      use of bacteriostatic lubricants in the usual dose before BCG instillation had no
      detectable adverse effect on the clinical efficacy of intravesical BCG
      immunotherapy. To avoid traumatic catheterization with possible systemic BCG
      administration, we therefore recommend, especially in men, the additional use of
      a sufficient quantity of urethral lubricant.

PMID- 11337291
TI  - Bladder preservation in adult classic exstrophy: early results of four patients.
AB  - OBJECTIVES: To report our experience with the treatment of classic exstrophy of
      the bladder in a small series of adult patients using ileocystoplasty, bladder
      neck reconstruction, and abdominal wall closure with flaps. The presentation of
      exstrophy of the bladder in adulthood is rare. The problems encountered include
      difficulty in abdominal closure, malignant potential, and upper tract
      dysfunction. The treatment of choice has been cystectomy with urinary diversion
      in all reported cases. METHODS: We treated 4 adult male patients with classic
      exstrophy of the bladder and complete epispadias. They had not received any
      previous treatment. Multiple random bladder biopsies revealed nonspecific
      inflammatory changes with focal areas of keratinization. Three patients were
      treated in two stages. The first stage included ileocystoplasty, bladder neck
      reconstruction, and abdominal wall closure with the use of flaps. The epispadias
      was repaired in the second stage. In 1 patient, the reconstruction was completed
      in a single stage. RESULTS: All patients were continent at the last follow-up
      visit, with three using self-catheterization and one voiding spontaneously. The
      renal parameters and ultrasound scans were normal at a follow-up of 2 to 48
      months. Cystoscopy performed at 6 months postoperatively revealed normal-looking
      mucosa in 2 patients and mild inflammation in 1 patient. Three patients were
      satisfied with the cosmetic results and one complained of the small size of his
      penis. All patients were evaluated by psychiatrists and revealed anxiety
      disorders preoperatively. After surgery, all demonstrated improved social
      interaction. CONCLUSIONS: Vesical preservation with primary reconstruction of
      bladder exstrophy in adults is safe and feasible in the absence of significant
      histologic changes in the bladder mucosa. Abdominal closure can be achieved
      without difficulty with the use of transposition flaps. However, these patients
      require strict follow-up to detect malignant transformation at an early stage.

PMID- 11337293
TI  - Incidence of concomitant procedures for pelvic organ prolapse and reconstruction
      in women who undergo surgery for stress urinary incontinence.
AB  - OBJECTIVES: To determine the incidence of concomitant procedures performed for
      pelvic organ prolapse or vaginal reconstruction at the time of surgery for stress
      urinary incontinence in contemporary practice. METHODS: We recorded all
      concomitant procedures for pelvic organ prolapse or vaginal reconstruction in 264
      women who underwent surgery for stress urinary incontinence at our institution
      from January 1995 to August 1997. RESULTS: Of 264 women, 111 (42%) had at least
      one concomitant procedure performed for pelvic organ prolapse or vaginal
      reconstruction, including 87 cystocele repairs, 31 rectocele repairs, 8
      sacrospinous fixations, 5 enterocele repairs, 5 abdominal sacrocolpopexies, 4
      perineoplasties, 3 urethral diverticulectomies, and 1 vaginal hysterectomy.
      Furthermore, 9% of patients had two or more procedures. CONCLUSIONS: We found
      that women who undergo surgery for stress urinary incontinence have a high
      incidence (42%) of associated pelvic organ prolapse requiring surgical repair.
      These additional repairs contribute to the overall success of surgery and should
      not be overlooked.

PMID- 11337294
TI  - Three-dimensional grayscale ultrasound: evaluation of prostate cancer compared
      with benign prostatic hyperplasia.
AB  - OBJECTIVES: To compare the accuracy of the detection, localization, and staging
      of prostate cancer using transrectal three-dimensional (3D) grayscale
      ultrasonography (3D-US) with conventional transrectal two-dimensional grayscale
      ultrasonography (2D-US). METHODS: Fifty patients with clinical localized prostate
      cancer scheduled to undergo radical retropubic prostatectomy and 50 patients with
      clinical benign prostatic hyperplasia underwent transrectal ultrasound
      investigations (2D and 3D). The prostate images were retrospectively analyzed by
      two ultrasound experts unaware of the clinical findings. The images of the
      prostate cancer group were correlated with the whole-mount histologic specimens
      of the prostate. RESULTS: All percentages are given for experts 1 and 2. The
      sensitivity, specificity, and accuracy for the detection of prostate cancer
      without considering the definitive localization of the tumor for 2D-US was 72%
      and 76%, 50% and 54%, and 63% and 64%, respectively; for 3D-US, the rates were
      82% and 88%, 40% and 42%, and 61% and 65%. The sensitivity, specificity, and
      accuracy of the combination of 2D-US with 3D-US was 88% and 90%, 36% and 38%, and
      62% and 64%, respectively. The sensitivity, specificity, and accuracy for the
      exact localization of the prostate tumor for 2D-US was 44% and 46%, 50% and 54%,
      and 47% and 50%, respectively; for 3D-US, they were 52% and 62%, 40% and 42%, and
      46% and 52%. The staging of prostate cancer using 3D-US was correct in 49%
      (expert 1) and in 57% (expert 2) of patients. No difference was observed between
      2D-US and 3D-US for accurate staging. Both experts judged the interpretation of
      3D-US images as superior to that of 2D-US images. CONCLUSIONS: Although 3D-US had
      statistically significant increased sensitivity in the detection of lesions and
      decreased specificity compared with 2D-US, 3D-US did not result in significant
      clinical improvement in the detection and staging of prostate cancer.

PMID- 11337295
TI  - Minimally invasive technique for sural nerve harvesting: technical description
      and follow-up.
AB  - OBJECTIVES: To provide instruction and the results of a minimally invasive
      technique for sural nerve harvesting in preparation for interposition nerve
      grafting during radical retropubic prostatectomy. METHODS: Twelve men underwent
      nerve harvesting performed using a tendon stripper. The short-form McGill Pain
      Questionnaire was completed preoperatively and at 6 months postoperatively.
      RESULTS: No significant morbidity from the leg resulted as a result of the sural
      nerve harvest. The results of the short-form McGill Pain Questionnaire
      demonstrated no significant sensory or affective changes in the leg. The average
      operative time for the entire harvesting procedure, including skin closure, was
      15 minutes. The estimated blood loss was less than 5 mL (range 2 to 10). No wound
      infection or skin erythema was observed. The discharge to home was not delayed
      compared with the usual length of stay after radical retropubic prostatectomy.
      CONCLUSIONS: This minimally invasive sural nerve harvesting technique is easy to
      perform and has minimal morbidity.

PMID- 11337296
TI  - Effect of local anesthetics on patient recovery after transrectal biopsy.
AB  - OBJECTIVES: To determine the analgesic efficacy of local anesthetics injected
      lateral to the seminal vesicles before prostate biopsy, during and immediately
      after the procedure, because pain is a common side effect of transrectal
      ultrasound-guided prostate biopsy. METHODS: Patients were randomized to receive 5
      mL of either 1% lidocaine or sterile normal saline injected (under ultrasound
      guidance) lateral to the seminal vesicles bilaterally before performance of the
      prostate biopsies, with the patient and physician unaware of the treatment group.
      Five minutes after the injection, a series of 12 prostate biopsies were
      performed. A visual analog scale (VAS) for pain at rest and with activity was
      obtained before the biopsy (preprocedure VAS) and immediately (intraprocedure
      VAS) and 30 minutes (postprocedure VAS) after the biopsy. Surveys examining the
      patients' expectations for biopsy pain were administered before and immediately
      after the biopsy. RESULTS: No significant differences were found between the
      groups with regard to demographic data, VAS pain scores at rest and with
      activity, and survey results. CONCLUSIONS: Injection of lidocaine lateral to the
      seminal vesicles before prostate biopsy did not diminish biopsy-associated pain.

PMID- 11337297
TI  - Are serum hormones associated with the risk of prostate cancer? Prospective
      results from the Massachusetts Male Aging Study.
AB  - OBJECTIVES: To determine whether prediagnostic serum hormones are predictive of
      prostate cancer risk in a sample of men 40 to 70 years old at baseline. METHODS:
      Seventeen serum hormones, including androgens, estrogens, and adrenal and
      pituitary hormones, were measured at baseline (1987 to 1989) and used to predict
      incident prostate cancer by follow-up (1995 to 1997) using data from the
      Massachusetts Male Aging Study, a prospective, population-based random sample.
      RESULTS: Seventy men (4%) of 1576 were diagnosed with prostate cancer between the
      baseline and follow-up periods (approximately 8 years). None of the hormones were
      associated with prostate cancer risk except for androstanediol glucuronide (AAG),
      which exhibited a nonlinear, inverse relationship with prostate cancer (P <0.003)
      when age, body mass index, alcohol use, dihydrotestosterone, and total prostate
      specific antigen were controlled for. Men in the second, third, and fourth
      quartiles of AAG relative to the first were less likely to be diagnosed with
      prostate cancer, although only the comparison of the second versus the first
      achieved statistical significance (odds ratio 0.2, 99% confidence interval 0.04
      to 0.6). No dose-response relationships were observed. CONCLUSIONS: The lack of
      association with most hormones and the nonlinear association with AAG calls into
      question whether serum hormones collected during midlife are risk factors for
      prostate cancer.

PMID- 11337298
TI  - Prognostic value of three molecular forms of prostate-specific antigen ratios in
      patients with prostate adenocarcinoma.
AB  - OBJECTIVES: To investigate whether different molecular forms of prostate-specific
      antigen (PSA) ratios could provide prognostic information about the stage and
      grade of prostate cancer. METHODS: Serum specimens were examined from 53 patients
      who underwent radical prostatectomy for clinically localized prostate cancer and
      from 94 patients diagnosed as having no evidence of malignancy (total PSA between
      4.1 and 20.0 ng/mL). The free/total PSA (fPSA/tPSA) ratio and complexed/total PSA
      (cPSA/tPSA) ratio in 18 patients with biochemical recurrence were compared with
      those of patients either without recurrence or with no evidence of malignancy.
      RESULTS: The fPSA/tPSA and cPSA/tPSA ratios differed significantly (P <0.05)
      between patients with organ-confined and those with non-organ-confined disease,
      but the tPSA, cPSA, and fPSA levels did not (P >0.05). The median values of the
      fPSA/tPSA ratio in patients with recurrence (7.0%) were significantly lower than
      in the patients without recurrence (8.9%) or those without evidence of malignancy
      (15.2%) (P = 0.02 and P <0.01, respectively). The median values of the cPSA/tPSA
      ratio in patients with recurrence (97.4%) were significantly higher than in
      patients without recurrence (92.9%) or those without evidence of malignancy
      (86.7%) (P <0.01 and P <0.01, respectively). At the time of recurrence, 6 (33%)
      of 18 patients expressed higher fPSA/tPSA ratios (15% or greater) and lower
      cPSA/tPSA ratios (less than 95%). Five (83%) of these 6 patients appeared to have
      aggressive tumors according to pathologic stage. CONCLUSIONS: The fPSA/tPSA and
      cPSA/tPSA ratios differed significantly among the three groups. Thus, a subset of
      tumors appears to be capable of producing high fPSA/tPSA and low cPSA/tPSA ratios
      at the time of recurrence, and some of these have an aggressive phenotype. Until
      this latter phenomenon can be adequately explained, use of these ratios for
      prognostic purposes should be approached cautiously.

PMID- 11337299
TI  - Results of a screening program for prostate cancer in patients scheduled for
      abdominoperineal resection for colorectal pathologic findings.
AB  - OBJECTIVES: Because of the difficulty of accessing the prostate for tissue
      sampling after surgical removal of the rectum and obliteration of the anus, we
      started an early detection program for prostate cancer in all men scheduled for
      abdominoperineal resection. METHODS: Twenty consecutive men were screened for
      prostatic adenocarcinoma before planned abdominoperineal resection for colorectal
      pathologic findings. Patients were 48 to 77 years old (mean 66.9). Screening
      included serum prostate-specific antigen determination and digital rectal
      examination. Those patients with suspicious findings underwent transrectal
      ultrasound-guided sextant biopsies of the prostate. RESULTS: One patient was
      excluded because of a prior history of prostate cancer. Six (31.6%) of the
      remaining 19 patients demonstrated elevated prostate-specific antigen levels
      (greater than 4.0 ng/mL); two of these patients also had an abnormal digital
      rectal examination. Transrectal ultrasound and prostate biopsies in these 6
      patients revealed prostatic adenocarcinoma in 3 patients (50% of those undergoing
      biopsies or 15.8% of those screened). The 13 patients who did not undergo
      prostate biopsies had prostate-specific antigen levels from 0.4 to 2.4 ng/mL
      (mean 0.9) and normal prostate glands according to the digital rectal
      examinations. CONCLUSIONS: Screening for prostate cancer in men 50 years old or
      older with 10 years or longer life expectancy before they undergo
      abdominoperineal resection detects a significant number of prostatic malignancies
      and should be encouraged.

PMID- 11337300
TI  - Routine cystoscopy before radical prostatectomy: is it justified?
AB  - OBJECTIVES: The extent of the required preoperative workup of patients who are
      candidates for radical prostatectomy is still controversial. Traditionally,
      cystoscopy has been reserved only for those patients who present with hematuria.
      However, several investigators have reported significant incidental cystoscopic
      findings among these patients and advocated the routine use of cystoscopy before
      radical prostatectomy. In view of the conflicting recommendations, we elected to
      assess the role of routine cystoscopy in a series of patients with prostate
      cancer at our institute. METHODS: We retrospectively reviewed the cystoscopic
      findings of 225 consecutive patients with organ-confined prostate carcinoma
      scheduled for radical prostatectomy. Rigid cystoscopy was performed before
      surgery either in an outpatient setting or on the operating table just before the
      operation. RESULTS: Significant cystoscopic findings were noted in 3 (1.3%) of
      225 patients. These included a bladder stone in 1 patient, superficial bladder
      tumor in 1 patient, and a post-sphincteric urethral polyp containing prostatic
      adenocarcinoma in a third patient. This polyp was resected transurethrally and
      the patient was treated thereafter with irradiation because of local extension.
      None of the 3 patients had microscopic hematuria on urinalysis to suggest the
      findings. Cystoscopy was uneventful in all patients, apart from occasional mild
      hematuria. CONCLUSIONS: These results show that the treatment of patients who
      were candidates for radical prostatectomy was affected by the findings of
      preoperative cystoscopy in less than 1% of the cases. We believe that in view of
      the low yield of cystoscopic findings in these patients, in an era in which cost
      effectiveness is a major issue, the routine use of cystoscopy before radical
      prostatectomy is not justified.

PMID- 11337301
TI  - Intraoperative T staging in radical retropubic prostatectomy: is it reliable?
AB  - OBJECTIVES: During radical prostatectomy, wide local excision of the lateral
      prostatic fascia and neurovascular bundle on the ipsilateral side of the tumor is
      advocated if nerve sparing is likely to result in a positive surgical margin. Our
      intent was to validate whether intraoperative T staging can predict the presence
      of positive surgical margins and aid in the decision of whether to perform nerve
      sparing prostatectomy. METHODS: One surgeon performed 100 consecutive radical
      prostatectomies, and one pathologist interpreted the pathologic findings.
      Topographic distribution of tumor within the specimen was assessed
      intraoperatively by palpation. The margin status was similarly assessed. This
      tactile clinical impression was compared with the final pathologic findings.
      RESULTS: The surgical margins were positive in 39 (39%) of 100 cases. The
      intraoperative assessment of the margin status had a high false-negative rate and
      a sensitivity of only 7%. However, the specificity was 96%, because few margins
      were falsely positive. The overall accuracy was 62%, with a negative predictive
      value of 62%. The sensitivity of the intraoperative assessment of tumor location
      was 73%, and the positive predictive value was 65%. CONCLUSIONS: The results of
      our study indicate that the intraoperative assessment of the margin status is not
      accurate and thus cannot help determine which patients require excision of the
      neurovascular bundle. We believe the decision to preserve the neurovascular
      bundle should be based on the preoperative prognostic factors and the presence of
      an intact capsule covering the region of the gland adjacent to this structure.

PMID- 11337302
TI  - Dose of radiation received by the bulb of the penis correlates with risk of
      impotence after three-dimensional conformal radiotherapy for prostate cancer.
AB  - OBJECTIVES: To evaluate the effect of the dose to the bulb of the penis on
      postradiation potency. METHODS: Twenty-one patients reporting potency before
      three-dimensional conformal radiotherapy had the dose delivered to the bulb of
      the penis evaluated. This was then compared with the patient assessments of post
      treatment sexual function to determine whether a dose-volume relationship exists.
      RESULTS: Among the patients analyzed to date, a strong dose-volume relationship
      and the likelihood of remaining potent after treatment seems to exist. Patients
      receiving a dose of less than 40 Gy to 70% of the bulb of the penis appear to
      have a much greater likelihood of maintaining potency. Patients receiving 70 Gy
      or more to 70% of the bulb of the penis appear to be at very high risk of
      experiencing radiation-induced impotence (P = 0.03). CONCLUSIONS: More studies
      are needed to confirm these observations. If confirmed, these data suggest that
      by using three-dimensional-based treatment planning and carefully designed
      treatment fields, the potency of men treated with radiotherapy might be
      substantially improved.

PMID- 11337304
TI  - Glansectomy: an alternative surgical treatment for Buschke-Lowenstein tumors of
      the penis.
AB  - OBJECTIVES: To present the surgical excision of the glans penis (glansectomy) as
      an alternative surgical treatment to penectomy. Buschke-Lowenstein tumors of the
      penis include the entities described in published reports as verrucous carcinoma
      and giant condyloma acuminatum of the penis. Both types are well-differentiated
      tumors, typically confined to the glans penis, with distinctly rare metastatic
      activity. METHODS: The study included 7 patients, 40 to 63 years of age, with
      exophytic, papillary lesions involving the glans penis. Biopsy led to the
      diagnosis of verrucous carcinoma in 4 patients and giant condyloma acuminatum in
      3 patients. All patients reported normal erectile function. Because of the low
      malignant potential of the tumor and its confinement to the glans penis, a simple
      glansectomy was performed in all patients to preserve the maximal penile length
      and functional integrity of the corpora cavernosa. RESULTS: The postoperative
      course was uncomplicated. With 18 to 65 months of follow-up, all patients were
      disease free. One patient required more aggressive treatment because of local
      recurrence of the tumor. All patients returned to normal sexual activity 1 month
      postoperatively. The only change during sexual activity, noted by two of the
      patients' partners, was vaginal pain, possibly due to the absence of the glans.
      CONCLUSIONS: Glansectomy may be considered the treatment of choice in patients
      with Buschke-Lowenstein tumors of the penis, with more radical techniques
      reserved for second-line treatment.

PMID- 11337303
TI  - Patient and partner satisfaction with Viagra (sildenafil citrate) treatment as
      determined by the Erectile Dysfunction Inventory of Treatment Satisfaction
      Questionnaire.
AB  - OBJECTIVES: To assess the efficacy and safety of Viagra (sildenafil citrate) in
      male outpatients with erectile dysfunction and patient and partner satisfaction
      with treatment using the Erectile Dysfunction Inventory of Treatment Satisfaction
      (EDITS). METHODS: A total of 247 patients with erectile dysfunction of broad
      spectrum etiology were treated in a randomized, double-blind, parallel-group,
      multicenter study conducted at outpatient clinics. Patients receiving oral
      sildenafil (25, 50, and 100 mg) were compared with patients receiving placebo
      during a 12-week period. The principal efficacy measures were responses to
      question 3 (ability to achieve an erection) and question 4 (ability to maintain
      an erection) on the International Index of Erectile Function and three global
      efficacy questions. Patient and partner satisfaction with treatment were
      assessed, for the first time, using the EDITS questionnaire. RESULTS: Efficacy
      scores for the International Index of Erectile Function questions and the global
      efficacy questions were significantly higher for patients receiving sildenafil
      than for those receiving placebo (P <0.001). Both patients and partners receiving
      sildenafil also had significantly higher EDITS scores than those receiving
      placebo (P <0.001). Adverse events were chiefly mild or moderate. Two patients
      receiving sildenafil and none receiving placebo discontinued treatment because of
      adverse events. CONCLUSIONS: Sildenafil was an effective, well-tolerated
      treatment for erectile dysfunction in an outpatient setting. Partner evaluations
      corroborated patient assessments. The results from the EDITS questionnaire
      indicated that after 12 weeks of receiving sildenafil both patients and partners
      reported higher levels of treatment satisfaction relative to placebo.

PMID- 11337305
TI  - Incidence of priapism in the general population.
AB  - OBJECTIVES: To assess the incidence of priapism in the general population.
      METHODS: We conducted a population-based retrospective cohort study within a
      general practitioners research database. Our study population comprised all male
      patients with permanent registration status with a general practitioner. All
      patients with an International Classification for Primary Care code for penile
      problems (Y01, Y04, Y08) were identified. In addition, a free text search on
      priapism and painful erection was conducted. The computerized medical records
      from all potential patients were reviewed, and we requested additional
      information from the general practitioner if priapism was suspected. RESULTS: The
      total study cohort comprised 145,071 men, with a total follow-up of 341,133
      person-years. Five patients developed a first occurrence of priapism during the
      follow-up period, corresponding to an overall incidence rate of 1.5 per 100,000
      person-years (95% confidence interval 0.2 to 2.8). The incidence rate in men 40
      years old and older was 2.9 per 100,000 person-years (95% confidence interval 0.1
      to 5.7). No cause of priapism was apparent in 2 patients, 2 cases occurred after
      intracavernous injection of vasodilators, and 1 patient experienced priapism
      because of sickle cell disease. CONCLUSIONS: The incidence of priapism is low but
      seems higher than was previously assumed.

PMID- 11337306
TI  - Endoscopic retrieval of retained Jackson-Pratt drain.
AB  - Jackson-Pratt (JP) drains are commonly used after urologic surgery. One of the
      complications associated with the use of JP drains occurs when the drain breaks,
      leaving the distal fenestrated part at the time of attempted removal. We describe
      the endoscopic retrieval of a retained JP drain, which was safely performed with
      local anesthesia and minimal risk.

PMID- 11337307
TI  - Single vaginal ectopic ureter and renal hypoplasia associated with urogenital
      sinus and abdominal muscular hypoplasia-a novel subtype of prune-belly syndrome
      in a female child?
AB  - We report a rare case that can be classified as prune-belly syndrome in a female.
      This patient came to our attention during the 19th week of gestation when massive
      ascites was found by ultrasound and the mother was transferred to our hospital.
      After birth, it was demonstrated that the infant had complicated anomalies,
      including abdominal muscular hypoplasia, urogenital sinus, a single, right-sided
      vaginal ectopic ureter, and hypoplasia of the right kidney. A sibling had a right
      hypoplastic kidney and right vesicoureteral reflux. Considering the combination
      of anomalies and the family history of urinary tract disease, her anomalies could
      be attributed to a genetic mutation.

PMID- 11337308
TI  - Prostate-specific antigen-all that rises is not refractory.
AB  - After the initiation of androgen suppression in men with prostate cancer, the
      serum prostate-specific antigen (PSA) level generally declines. A subsequent PSA
      rise during that suppression usually reflects the presence of a significant
      component of hormonally refractory prostate cancer. We report a patient with a
      rising PSA level and elevated testosterone level after depot leuprolide in whom
      the PSA level subsequently declined with administration of bicalutamide.

PMID- 11337309
TI  - A rare case of renal hemangioma presenting as polycythemia.
AB  - Instances of renal cell carcinoma and erythropoietin-producing renal cysts
      presenting as polycythemia are well documented. To our knowledge, no case of
      hemangioma presenting as polycythemia has been reported. We present a case of a
      39-year-old man with a 5-year history of polycythemia requiring phlebotomy every
      3 months. Computed tomography revealed a 6 to 7-cm right upper pole renal mass.
      The patient underwent right radical nephrectomy, and pathologic examination
      revealed the mass to be a capillary hemangioma. The patient has not required
      phlebotomy for 1 year since the removal of the hemangioma.

PMID- 11337310
TI  - Surgical management of renal cell carcinoma invading into the liver: radical
      nephrectomy en bloc with right hepatic lateral sector.
AB  - Renal cell carcinoma demonstrates expansive growth and invasion of adjacent
      structures. Direct liver extension, although uncommon, is a dismal prognostic
      sign. We propose radical nephrectomy en bloc with right lateral sector (segments
      6 and 7) of the liver. The operative procedure was performed in 2 male patients,
      61 and 81 years of age, both with renal cell carcinoma and direct hepatic
      extension. The patients had no evidence of disease at 100 and 57 months after
      resection. This procedure may help cure selected patients with renal cell
      carcinoma invading the liver.

PMID- 11337311
TI  - Laparoscopic and computed tomography-guided percutaneous radiofrequency ablation
      of renal tissue: acute and chronic effects in an animal model.
AB  - OBJECTIVES: To evaluate the laparoscopic and percutaneous delivery of impedance
      based radiofrequency ablation (RFA) of the kidney by studying the acute and
      chronic clinical, radiographic, and histopathologic effects in the porcine model.
      METHODS: Eight kidneys from 4 pigs underwent laparoscopic RFA. Six kidneys from 3
      additional pigs received computed tomography (CT)-guided, percutaneous RFA. CT
      scans were performed immediately after RFA and before harvest at 2 hours, 24
      hours, 3 weeks, and 13 weeks. The gross, radiographic, and histopathologic
      changes were recorded for each period. RESULTS: Grossly, the RFA lesions were
      sharply demarcated, measuring 3 to 5 cm. Two major complications (14%) occurred
      (one urinoma, one psoas muscle injury) in 14 ablations. No deaths or significant
      blood loss occurred as a result of RFA. Radiographically, the immediate CT
      scanning demonstrated small perinephric hematomas and wedge-shaped defects.
      Delayed CT showed nonenhancing defects up to 5 cm. Color-flow and power Doppler
      were unable to distinguish significant tissue changes during RFA. The
      histopathologic evaluation revealed marked inflammation surrounding the necrotic
      regions in the early lesions; chronic lesions were characterized by dense
      fibrosis. The tissue temperatures ranged from 62 degrees to 118 degrees C in the
      area of ablation. CONCLUSIONS: RFA is readily delivered laparoscopically or
      percutaneously with minimal morbidity. Impedance-based application of
      radiofrequency energy allows monitoring and control of ablation. Using a multi
      antenna probe, areas of tissue up to 5 cm can be completely destroyed. The RFA
      lesion can be monitored as a nonenhancing cortical defect on CT.

PMID- 11337312
TI  - Evaluation of cell proliferation, apoptosis, and angiogenesis in transitional
      cell carcinoma of the renal pelvis and ureter.
AB  - OBJECTIVES: To investigate cell proliferation, apoptosis, and angiogenesis and
      their roles in transitional cell carcinoma (TCC) of the renal pelvis and ureter.
      METHODS: Formalin-fixed and paraffin-embedded tissue blocks from 42 patients with
      TCC of the renal pelvis and ureter were studied. Cell proliferation was assessed
      by Ki-67 immunostaining, and the proliferation index (PI) was expressed as a
      percentage of Ki-67-positive cells. Apoptosis was detected by terminal
      deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL), and
      the apoptotic index (AI) was expressed as a percentage of TUNEL positive cells.
      Angiogenesis was evaluated by CD31 immunostaining, and microvessel density (MVD)
      was expressed as the average of the microvessel count. RESULTS: The PI ranged
      from 5.9% to 48.0% (median 20.03%), AI from 1.0% to 4.2% (median 2.26%), and MVD
      from 16.0 to 146.0 (median 56.88) in TCC of the renal pelvis and ureter.
      Statistical analysis revealed close associations of both PI and MVD with tumor
      stage and of AI with tumor grade. Our study demonstrated a strong relationship
      between PI and MVD, but did not show associations of AI with PI or MVD in TCC of
      the renal pelvis and ureter. CONCLUSIONS: It is suggested that the high activity
      of tumor cell proliferation with rich neovascularization may be related to the
      high malignant potential of the cancer, and evaluation of cell proliferation
      combined with angiogenesis may be useful in predicting the progression of the
      renal pelvic and ureteral TCC.

PMID- 11337313
TI  - Detection of chromosomal imbalances in papillary bladder tumors by comparative
      genomic hybridization.
AB  - OBJECTIVES: To identify those genetic alterations that are associated with
      bladder cancer invasion and progression. METHODS: A total of 30 specimens of
      transitional cell carcinoma of the bladder were analyzed by comparative genomic
      hybridization. The results were compared and summarized with previously reported
      studies. RESULTS: The most frequent chromosome changes detected in our series of
      tumors were losses in 9q, 9p, 8p, and 11p and gains in 8q, 1q, 20q, and 11q.
      Three regions of deletion on chromosome 9 were delineated, at 9p21-p22, 9q13-q22,
      and 9q31-q34. Gains in 1q and losses on 11p were significantly more frequent in
      pT1G2 tumors than in superficial (pTa) ones. In our study, the most striking
      differences were seen between pT1G3 and pT1G2 tumors. Gains on 10p and 6p and
      losses at 5q, 6q, and 18q were significantly more frequent in the former.
      CONCLUSIONS: A summary of our results and those available from published reports
      suggest that several groups of chromosomal imbalances may be associated with
      specific steps along bladder cancer progression. These genetic changes assume two
      different patterns: those that are shared, but are more intensive in one stage
      than in the other, and those such as a gain on 3p that are unique to invasive
      tumors.

PMID- 11337314
TI  - Increased intracellular doxorubicin by anti-FAS monoclonal antibody: a mechanism
      that enhances the cytotoxicity in renal cell carcinoma cells.
AB  - OBJECTIVES: To investigate the effect of anti-Fas monoclonal antibody (mAb) on
      the intracellular concentration of doxorubicin in renal cell carcinoma (RCC)
      cells. Little is known about the influence of anti-Fas mAb on the intracellular
      concentration of chemotherapeutic agents. METHODS: The concentration of
      intracellular doxorubicin was determined by high-performance liquid
      chromatography. The mRNA and protein levels of multidrug resistance-associated
      protein gene were evaluated by reverse transcriptase-polymerase chain reaction
      and immunocytochemistry, respectively. RESULTS: An increased concentration of
      doxorubicin inside the cells was found: 2.4-fold in ACHN cells (a human RCC cell
      line) after treatment with doxorubicin combined with anti-Fas mAb compared with
      doxorubicin alone. Of the five cases of freshly derived RCC cells treated with
      doxorubicin and anti-Fas mAb, the intracellular concentration of doxorubicin was
      increased 2.3 and 2.7-fold in two of them, respectively. Furthermore, both the
      mRNA and the protein levels of the multidrug resistance-associated protein gene
      were downregulated after treatment of ACHN cells with anti-Fas mAb. Treatment of
      ACHN cells with a combination of anti-Fas mAb and doxorubicin resulted in a
      potentiation of the doxorubicin-mediated cytotoxicity. CONCLUSIONS: The increased
      intracellular concentration of doxorubicin by anti-Fas mAb might be one of the
      mechanisms responsible for the enhancement of doxorubicin-mediated cytotoxicity
      in RCC cells.

PMID- 11337315
TI  - Tissue effects of saw palmetto and finasteride: use of biopsy cores for in situ
      quantification of prostatic androgens.
AB  - OBJECTIVES: To determine the effects of a saw palmetto herbal blend (SPHB)
      compared with finasteride on prostatic tissue androgen levels and to evaluate
      needle biopsies as a source of tissue for such determinations. METHODS: Prostate
      levels of testosterone and dihydrotestosterone (DHT) were measured on 5 to 10-mg
      biopsy specimens (18-gauge needle cores) in three groups of men with symptomatic
      benign prostatic hyperplasia: 15 men receiving chronic finasteride therapy versus
      7 untreated controls; 4 men undergoing prostate adenomectomy to determine
      sampling variability (10 specimens each); and 40 men participating in a 6-month
      randomized trial of SPHB versus placebo, before and after treatment. RESULTS:
      Prostatic tissue DHT levels were found to be several times higher than the levels
      of testosterone (5.01 versus 1.51 ng/g), that ratio becoming reversed (1.05
      versus 3.63 ng/g) with chronic finasteride therapy. The finasteride effect was
      statistically significant for both androgens (P <0.01), and little overlap of
      individual values between finasteride-treated and control patients was seen. In
      the randomized trial, tissue DHT levels were reduced by 32% from 6.49 to 4.40
      ng/g in the SPHB group (P <0.005), with no significant change in the placebo
      group. CONCLUSIONS: For control versus finasteride-treated men, the tissue
      androgen values obtained with needle biopsy specimens were similar-both for
      absolute values and the percentage of change-to those previously reported using
      surgically excised volumes of prostatic tissue. The quantification of prostatic
      androgens by assay of needle biopsies is thus feasible and offers the possibility
      of serial studies in individual patients. The SPHB-induced suppression of
      prostatic DHT levels, modest but significant in a randomized trial, lends an
      element of support to the hypothesis that inhibition of the enzyme 5-alpha
      reductase is a mechanism of action of this substance.

PMID- 11337316
TI  - Reverse transcriptase-polymerase chain reaction for prostate-specific antigen in
      the molecular staging of pelvic surgical margins after radical prostatectomy.
AB  - OBJECTIVES: To examine the application of reverse transcriptase-polymerase chain
      reaction (RT-PCR) to assist in prostate-specific antigen (PSA) detection in the
      surgical margins after radical prostatectomy (RP). The risk of local recurrence
      increases considerably in the presence of extracapsular tumor growth and/or
      positive surgical margins at RP. Although this makes it possible to identify
      patients with an increased risk of local recurrence, precise predictions cannot
      be made. A more precise assessment is desirable mainly for early planning of
      adjuvant therapy. METHODS: Ninety-five patients with clinically organ-confined
      prostate cancer (CaP) underwent RP. After removing the gland, biopsies were
      obtained from four defined areas of the prostatic fossa and processed for RT-PCR
      for PSA detection. Sixteen patients with muscle-invasive bladder carcinoma who
      underwent radical cystoprostatectomy served as controls. RESULTS: Thirty-two of
      95 patients with CaP (35%) had at least one positive molecular margin indicating
      an expression for PSA; 19 of 48 (39%) of these had an organ-confined tumor stage
      according to conventional histology and 13 of 47 (28%) had tumor growth beyond
      the prostate. A statistically significant correlation between the frequency of
      positive molecular margins and clinical data was only observed in the group with
      disease greater than Stage pT2. All controls had negative molecular margins (P =
      0.012). CONCLUSIONS: On the basis of the results obtained, molecular diagnostic
      RT-PCR for PSA detection in the surgical margins after RP seems to be an
      interesting supplementary tool for monitoring the course and establishing the
      prognosis. Long-term follow-up of these patients is needed to demonstrate the
      clinical value of molecular diagnostics of surgical margins during RP.

PMID- 11337317
TI  - Fluid-attenuated inversion recovery now with another acronym: "KRISP FLAIR".

PMID- 11337318
TI  - MR perfusion imaging of hyperacute stroke.

PMID- 11337319
TI  - Tuning in on tumor activity with proton MR spectroscopy.

PMID- 11337320
TI  - Prospective evaluation of the brain in asymptomatic children with
      neurofibromatosis type 1: relationship of macrocephaly to T1 relaxation changes
      and structural brain abnormalities.
AB  - BACKGROUND AND PURPOSE: Mutation of the neurofibromatosis type 1 (NF-1) gene may
      be associated with abnormal growth control in the brain. Because macrocephaly
      could be a sign of abnormal brain development and because 30% to 50% of children
      with NF-1 display macrocephaly in the absence of hydrocephalus, we sought to
      determine the relationship between macrocephaly and other brain abnormalities in
      young subjects with NF-1. These subjects were free of brain tumor, epilepsy, or
      other obvious neurologic problems. METHODS: We prospectively screened 18
      neurologically asymptomatic subjects with NF-1, ages 6 to 16 years, using
      clinical measures, psychometric testing, conventional MR imaging, and
      quantitative MR imaging to measure T1. RESULTS: Cranial circumference was 2 or
      more SDs above the age norm in seven (39%) of 18 subjects, a frequency of
      macrocephaly 17-fold higher than normal. Conventional MR imaging showed
      abnormalities in all 18 children, although there were more extensive
      abnormalities in subjects with macrocephaly. Macrocephaly in NF-1 was associated
      with enlargement of multiple brain structures, and brain T1 in macrocephalic
      subjects was reduced with respect to controls in the genu, frontal white matter,
      caudate, putamen, thalamus, and cortex. In normocephalic subjects, T1 was reduced
      only in the genu and splenium. Volumetric analysis showed that macrocephaly was
      associated specifically with enlargement of white matter volume. CONCLUSION:
      Neurologically asymptomatic children with NF-1 showed macrocephaly, cognitive
      deficit, enlarged brain structures, and abnormally low brain T1. Macrocephaly in
      children with NF-1 may be associated with characteristic alterations in brain
      development, marked by more widespread and significant changes in T1, greater
      enlargement of midline structures, and greater volume of white matter.

PMID- 11337321
TI  - Combined intraarterial carboplatin, intraarterial etoposide phosphate, and IV
      Cytoxan chemotherapy for progressive optic-hypothalamic gliomas in young
      children.
AB  - BACKGROUND AND PURPOSE: Optic pathway and/or hypothalamic astrocytomas in
      children are often quiescent, but in some cases, more aggressive tumors may cause
      progressive visual, endocrine, and neurologic deterioration. The initial
      treatment of these gliomas includes surgery and IV chemotherapy. Radiotherapy is
      not recommended in young children because of its severe adverse effects on
      cognitive and neuroendocrine function. This report suggests a new approach using
      combined intraarterial and IV carboplatin-based chemotherapy for patients for
      whom first line treatment has already failed. METHODS: Six children (mean age, 57
      months) with the diagnosis of optic pathway hypothalamic gliomas, who had tumor
      progression after surgery and underwent IV chemotherapy, were treated monthly
      with intraarterially administered carboplatin, intraarterially administered
      etoposide phosphate, and IV administered Cytoxan. Four of the children had
      histologically verified pilocytic astrocytomas, and in two cases, diagnosis was
      made on the basis of clinical findings. Administration of the intraarterial
      chemotherapy required catheter placement in both internal carotid arteries at the
      level of C2-C3 and into one of the vertebral arteries at the level of C6-C7, with
      the patient under general anesthesia. RESULTS: Four of six patients had partial
      radiographic response, one had stable disease, and one had progressive disease
      after one cycle. Three patients showed clinical improvement. There were no
      serious complications associated with the angiographic procedures. Toxicities
      included bronchospasm that resolved after 3 to 4 minutes in one patient. One
      patient showed mild ototoxicity, and four patients needed platelet transfusion
      because of hematologic toxicity of drugs. CONCLUSION: These results suggest that
      this modality of chemotherapy (administered after failure of systemic [ie, IV]
      chemotherapy), of progressive optic-hypothalamic astrocytomas in young children
      may be an effective treatment prior to radiotherapy.

PMID- 11337322
TI  - Lhermitte-Duclos disease: assessment with MR imaging, positron emission
      tomography, single-photon emission CT, and MR spectroscopy.
AB  - SUMMARY: Lhermitte-Duclos disease (LDD) is a rare cerebellar lesion with features
      of both malformation and benign neoplasm. However, the fundamental nature of the
      entity, its pathogenesis, and the exact genetic alterations remain unknown. We
      describe MR findings (including perfusion- and diffusion-weighted images) in two
      patients with LDD, as well as findings from single-photon emission CT (SPECT), MR
      spectroscopy (MRS), and fluorodeoxyglucose (FDG) positron emission tomography
      (PET) that give additional information about tumor pathophysiology. MR imaging
      usually distinguishes the LDD by its characteristic "tiger-striped" appearance.
      The regions of increased regional cerebral blood volume (rCBV) within the lesion
      correlated closely to the regions of FDG-hypermetabolism and high thallium (201
      Tl) uptake. Proton MRS revealed an increased level of lactate and decreased level
      of myo-inositiol and N-acetyl-aspartate, as observed in low-grade gliomas, but
      decreased levels of choline. Our cases indicate that the functional
      investigations give additional information about tumor pathophysiology and
      reflect the histopathologic controversial entity with both characteristics found
      in low-grade gliomas and characteristics not typical for tumors.

PMID- 11337323
TI  - Multi-slice proton MR spectroscopy and diffusion-weighted imaging in
      methylmalonic acidemia: report of two cases and review of the literature.
AB  - SUMMARY: Methylmalonic acidemia is an inborn disorder of amino acid metabolism
      that commonly presents with neurologic deficits. We present the results of multi
      slice proton MR spectroscopy and diffusion-weighted imaging of the brain in two
      patients with methylmalonic acidemia. The findings consisted of restricted
      diffusion and elevated lactate in the globi pallidi, compatible with acute
      infarction (patient 1) and elevated lactate in CSF (patient 2).

PMID- 11337324
TI  - Localized proton MR spectroscopy in infants with urea cycle defect.
AB  - SUMMARY: Urea cycle defect is an inborn error of ammonium metabolism caused by a
      deficient activity of the enzymes involved in urea synthesis. Localized short-TE
      proton MR spectroscopy, performed in two infants who had citrullinemia and
      ornithine transcarbamylase deficiency, respectively, showed a prominent increase
      of glutamine/glutamate and lipid/lactate complex in both cases. N
      acetylaspartate, total creatine, and myo-inositol were decreased in the infant
      with citrullinemia. Proton MR spectroscopy provided useful information for the
      diagnosis and understanding of the pathophysiology of urea cycle enzyme defect.

PMID- 11337325
TI  - Anomalous facial nerve canal with cochlear malformations.
AB  - BACKGROUND AND PURPOSE: Anteromedial "migration" of the first segment of the
      facial nerve canal has been previously identified in a patient with a non-Mondini
      type cochlear malformation. In this study, several patients with the same facial
      nerve canal anomaly were reviewed to assess for the association and type of
      cochlear malformation. METHODS: CT scans of the temporal bone of 15 patients with
      anteromedial migration of the first segment of the facial nerve canal were
      collected from routine departmental examinations. In seven patients, the
      anomalous course was bilateral, for a total of 22 cases. The migration was graded
      relative to normal as either mild/moderate or pronounced. The cochlea in each of
      these cases was examined for the presence and size of the basilar, second, and
      apical turns. The turns were either absent, small, normal, or enlarged. The CT
      scans of five patients with eight Mondini malformations were examined for
      comparison. RESULTS: The degree of the facial nerve migration was pronounced in
      nine cases and mild/moderate in 13. All 22 of these cases had associated cochlear
      abnormalities of the non-Mondini variety. These included common cavity anomalies
      with lack of definition between the cochlea and vestibule (five cases), cochleae
      with enlarged basilar turns and absent second or third turns (five cases), and
      cochleae with small or normal basilar turns with small or absent second or third
      turns (12 cases). None of the patients with Mondini-type cochlear malformations
      had anteromedial migration of the facial nerve canal. CONCLUSION: Anteromedial
      migration of the facial nerve canal occurs in association with some cochlear
      malformations. It did not occur in association with the Mondini malformations. A
      cochlea with a Mondini malformation, being similar in size to a normal cochlea,
      may physically prohibit such a deviation in course.

PMID- 11337326
TI  - Diameter of the bony lacrimal canal: normal values and values related to
      nasolacrimal duct obstruction: assessment with CT.
AB  - BACKGROUND AND PURPOSE: Epiphora, or tearing due to primary acquired nasolacrimal
      duct obstruction (PANDO), is increasingly being treated with balloon dilatation.
      The cause of PANDO is unknown, but a small diameter of the bony nasolacrimal
      canal might be one of the etiologic factors. The purpose of this study was to
      determine the normal distribution of diameters of the bony canal and to ascertain
      whether there is an association between the diameter of the bony canal and
      primary nasolacrimal duct obstruction. METHODS: Using axial CT, we measured the
      minimum diameter of the bony nasolacrimal canal in a control group of 50 men and
      50 women and in 19 patients with PANDO. RESULTS: The mean minimum diameter in the
      control group was 3.5 mm, which was smaller than expected on the basis of
      published data. The difference between the mean minimum diameter in men (3.70 mm)
      and that in women (3.35 mm) was significant. The mean minimum diameter in the
      patient group was 3.0 mm, which was significantly smaller than that in the
      control group. There was, however, considerable overlap. CONCLUSION: A small
      diameter of the bony canal appears to be one of the etiologic factors in PANDO.

PMID- 11337327
TI  - Synovial sarcomas of the head and neck: CT and MR imaging findings of eight
      patients.
AB  - BACKGROUND AND PURPOSE: Synovial sarcomas are soft-tissue tumors that rarely
      occur in the head and neck. The purpose of this study was to evaluate their CT
      and MR imaging appearance and to show that they may have a surprisingly benign
      imaging appearance. METHODS: Eight patients with histologically proved synovial
      sarcoma underwent CT; additionally, MR imaging examinations were performed in
      five of the eight cases. Attenuation and signal intensity on CT scans and MR
      images, respectively, were studied by two radiologists. They analyzed the
      location, size, margins, homogeneity, presence of adenopathies and infiltrative
      signs, and enhancement after injection of contrast medium. RESULTS: Four tumors
      were located in the hypopharynx, two arose from the infratemporal fossa, one
      arose from the maxillary sinus, and one arose from the faucial tonsil. Tumor
      sizes ranged from 27 to 70 mm. On CT scans and MR images, six lesions were
      homogeneous and well defined, with smooth margins. The remaining tumors were
      heterogeneous. In two cases, adjacent tissues were invaded. Calcifications were
      observed in one case and adenopathy in two cases. In three cases, the lesions
      were isointense on T1-weighted MR images and hypointense on T2-weighted MR
      images, and in the other two cases in which MR imaging was performed, the lesions
      were both isointense and hypointense on both T1- and T2-weighted images. Only the
      two local recurrent lesions were multilocular. CONCLUSION: Synovial sarcomas are
      aggressive sarcomas that may appear "benign" in some cases. In a young man, a
      synovial sarcoma may be suspected when a well-demarcated, homogeneous lesion is
      found in the head and neck.

PMID- 11337328
TI  - Mycotic aneurysm and cerebral infarction resulting from fungal sinusitis: imaging
      and pathologic correlation.
AB  - SUMMARY: A 73-year-old man was admitted with invasive aspergillus of the sphenoid
      sinus. Endoscopic debridement of the sphenoid sinus was complicated by rupture of
      a mycotic cavernous carotid artery aneurysm with severe epistaxis. The aneurysm
      was closed emergently by endovascular coil placement. Subsequently, the mycotic
      aneurysm extended intradurally and caused fatal subarachnoid hemorrhage. The
      radiologic-pathologic data illustrate the mechanism of fungal mycotic aneurysm
      formation and growth. This case emphasizes the need for rapid diagnosis of
      potential fungal involvement of the central nervous system and suggests the
      necessity for aggressive treatment once fungal cerebrovascular involvement is
      identified.

PMID- 11337329
TI  - Bilateral internal carotid aneurysms presenting as a nonpulsatile parapharyngeal
      mass: complementary diagnosis by CT, MR imaging, and digital subtraction
      angiography.
AB  - SUMMARY: We report fusiform aneurysms in both internal carotid arteries in a 74
      year-old man who presented with a nonpulsatile retropharyngeal mass. Both helical
      CT and MR imaging disclosed the nature of the lesions. Arteriography, required
      for therapeutic decisions, confirmed the diagnosis. Because of the rarity of this
      condition and the potential for misdiagnosis, we describe the findings on
      complementary radiologic examinations.

PMID- 11337330
TI  - Combined benign odontogenic tumors: CT and MR findings and histomorphologic
      evaluation.
AB  - SUMMARY: Calcifying epithelial odontogenic tumors and calcifying odontogenic
      cysts are rare, benign odontogenic tumors. We report two cases of an exceptional
      combination of these tumors with either an ameloblastic fibroodontoma or an
      odontoma.

PMID- 11337331
TI  - Intracranial giant cell reparative granuloma arising from the temporal lobe area:
      MR findings.
AB  - SUMMARY: We present an unusual case of a giant cell reparative granuloma arising
      from the left temporal lobe area of a 38-year-old man and provide clinical and MR
      findings. Current diagnosis and treatment options are also discussed.

PMID- 11337332
TI  - Tumefactive fibroinflammatory lesion of the neck with progressive invasion of the
      meninges, skull base, orbit, and brain.
AB  - SUMMARY: Tumefactive fibroinflammatory lesions of the head and neck are rare. CNS
      involvement has not been reported. We present a histologically proven case of a
      tumefactive fibroinflammatory lesion that originated in the left side of the neck
      and progressed over 2 years to involve the meninges, the cavernous sinuses, the
      right temporal lobe, and the right orbit. The lesion caused destruction of the
      skull base and a subdural hematoma. The relationship of the present lesion to
      idiopathic hypertrophic pachymeningitis and Tolosa-Hunt syndrome is discussed.

PMID- 11337333
TI  - MR imaging in two cases of subacute denervation change in the muscles of facial
      expression.
AB  - SUMMARY: Denervation changes in muscle following damage to cranial and peripheral
      nerves can be observed on both CT and MR imaging studies. These findings are well
      described for cranial nerves (CN) V, X, XI, and XII. The CT findings of
      denervation atrophy due to CN VII dysfunction have been reported. We describe the
      MR imaging findings in two patients with perineural spread of tumor along CN VII.
      Both patients showed T2 prolongation and postcontrast enhancement in muscles of
      facial expression, suggestive of subacute denervation changes.

PMID- 11337334
TI  - The parasagittal line: an anatomic landmark for axial imaging.
AB  - BACKGROUND AND PURPOSE: No validated imaging landmark exists for characterizing
      the medial-lateral position of abnormalities at the high convexity-parasagittal
      region. Our understanding of the courses and deflections of the upper cerebral
      sulci is limited. Our purpose, therefore, was to define a frontooccipital line
      with reproducible anatomic relations to the upper cerebral gyri and sulci and to
      validate that line for use as an anatomic landmark by specific analysis of the
      gyral-sulcal relationships along it. METHODS: In 100 subjects of all ages, the
      gyri and sulci visualized on serial axial CT sections of the upper brain were
      traced onto a single flat surface to delineate the anatomic relationships among
      the midline interhemispheric fissure, the paramedian superior frontal sulci (SFS)
      and intraoccipital sulci (IOS), the medial surface sulci, the high convexity
      sulci, and the inner table of the skull. These tracings provided a template for
      drawing a straight, best-fit parasagittal line from the SFS to the IOS and for
      assessing how reproducibly key anatomic structures align along the parasagittal
      line. To assure the applicability of the line to MR imaging, selected
      relationships were retested on serial axial MR sections in the same subjects.
      RESULTS: The parasagittal line could be drawn in each case and showed
      reproducible alignment with the SFS, hand-motor area, partes marginales, pars
      deflections, postcentral "parentheses," distal intraparietal sulci, and IOS. In
      supraventricular sections, the parasagittal line separated the sulci arising
      along the medial surface from those arising along the convexity. CONCLUSION:
      Because the anatomic relationships of the parasagittal line are reproducible, it
      may serve as a reference line or landmark. The tendency of this line to demarcate
      medial sulci from convexity sulci suggests immediate application to the
      definition of vascular territories and vascular watersheds, a topic under active
      investigation.

PMID- 11337335
TI  - Reduction of CSF and blood flow artifacts on FLAIR images of the brain with k
      space reordered by inversion time at each slice position (KRISP).
AB  - BACKGROUND AND PURPOSE: Our purpose was to test a new variant of the fluid
      attenuated inversion-recovery (FLAIR) sequence that was designed to reduce CSF
      and blood flow artifacts by use of a non-slice-selective inversion pulse and k
      space reordered by inversion time at each slice position (KRISP). METHODS: With
      the KRISP FLAIR sequence, the slice order was cycled so that each inversion time
      (TI) was associated with a region of k-space rather than a particular slice, and
      the effective inversion time (TI(eff)) was chosen to null the signal from CSF.
      Scans were obtained with both conventional and KRISP FLAIR sequences. Studies
      were performed in 20 adult patients with a variety of brain diseases. Images were
      evaluated for artifacts from patient motion, CSF, and blood flow, and scored on a
      four-point scale. The conspicuity of the cortex, meninges, ventricular system,
      brain stem, and cerebellum was evaluated, as was lesion number and conspicuity.
      RESULTS: The KRISP FLAIR sequence showed more patient motion artifacts but had a
      pronounced advantage over the conventional sequence in control of CSF artifacts
      around the foramen of Munro, in the third ventricle, aqueduct, and fourth
      ventricle, as well as in the basal cisterns and around the brain stem and
      cerebellum. Blood flow artifacts from the internal carotid, basilar, and
      vertebral arteries were also much better controlled. Spurious high signal in the
      sylvian branches of the middle cerebral artery was eliminated. The meninges,
      cortex, ventricular system, brain stem, and cerebellum were better seen due to
      improved artifact suppression and an edge enhancement effect. CONCLUSION: The
      KRISP FLAIR sequence can suppress CSF and blood flow artifacts and improve the
      conspicuity of the meninges, cortex, brain stem, and cerebellum. Its major
      disadvantage is its duration, which may be reducible with a fast spin-echo
      version.

PMID- 11337336
TI  - Simultaneous measurement of regional cerebral blood flow by perfusion CT and
      stable xenon CT: a validation study.
AB  - BACKGROUND AND PURPOSE: Knowledge of cerebral blood flow (CBF) alterations in
      cases of acute stroke could be valuable in the early management of these cases.
      Among imaging techniques affording evaluation of cerebral perfusion, perfusion CT
      studies involve sequential acquisition of cerebral CT sections obtained in an
      axial mode during the IV administration of iodinated contrast material. They are
      thus very easy to perform in emergency settings. Perfusion CT values of CBF have
      proved to be accurate in animals, and perfusion CT affords plausible values in
      humans. The purpose of this study was to validate perfusion CT studies of CBF by
      comparison with the results provided by stable xenon CT, which have been reported
      to be accurate, and to evaluate acquisition and processing modalities of CT data,
      notably the possible deconvolution methods and the selection of the reference
      artery. METHODS: Twelve stable xenon CT and perfusion CT cerebral examinations
      were performed within an interval of a few minutes in patients with various
      cerebrovascular diseases. CBF maps were obtained from perfusion CT data by
      deconvolution using singular value decomposition and least mean square methods.
      The CBF were compared with the stable xenon CT results in multiple regions of
      interest through linear regression analysis and bilateral t tests for matched
      variables. RESULTS: Linear regression analysis showed good correlation between
      perfusion CT and stable xenon CT CBF values (singular value decomposition method:
      R(2) = 0.79, slope = 0.87; least mean square method: R(2) = 0.67, slope = 0.83).
      Bilateral t tests for matched variables did not identify a significant difference
      between the two imaging methods (P >.1). Both deconvolution methods were
      equivalent (P >.1). The choice of the reference artery is a major concern and has
      a strong influence on the final perfusion CT CBF map. CONCLUSION: Perfusion CT
      studies of CBF achieved with adequate acquisition parameters and processing lead
      to accurate and reliable results.

PMID- 11337337
TI  - Benefits of perfusion MR imaging relative to diffusion MR imaging in the
      diagnosis and treatment of hyperacute stroke.
AB  - BACKGROUND AND PURPOSE: The development of thrombolytic agents for use with
      compromised cerebral blood flow has made it critical to quickly identify those
      patients to best treat. We hypothesized that combined diffusion and perfusion MR
      imaging adds vital diagnostic value for patients for whom the greatest potential
      benefits exist and far exceeds the diagnostic value of diffusion MR imaging
      alone. METHODS: The cases of patients with neurologic symptoms of acute ischemic
      stroke who underwent ultra-fast emergent MR imaging within 6 hours were reviewed.
      In all cases, automatic processing yielded isotropic diffusion images and
      perfusion time-to-peak maps. Images with large vessel distribution ischemia and
      with mismatched perfusion abnormalities were correlated with patient records. All
      follow-up images were reviewed and compared with outcomes resulting from
      hyperacute therapies. RESULTS: For 16 (26%) of 62 patients, hypoperfusion was the
      best MR imaging evidence of disease distribution, and for 15 of the 16,
      hypoperfusion (not abnormal diffusion) comprised the only imaging evidence for
      disease involving large vessels. For seven patients, diffusion imaging findings
      were entirely normal, and for nine, diffusion imaging delineated abnormal signal
      in either small vessel distributions or in a notably smaller cortical branch in
      one case. In all cases, perfusion maps were predictive of eventual lesions, as
      confirmed by angiography, CT, or subsequent MR imaging. CONCLUSION: If only
      diffusion MR imaging is used in assessing patients with hyperacute stroke, nearly
      one quarter of the cases may be incorrectly categorized with respect to the
      distribution of ischemic at-risk tissue. Addition of perfusion information
      further enables better categorizing of vascular distribution to allow the best
      selection among therapeutic options and to improve patient outcomes.

PMID- 11337338
TI  - Abnormal magnetization transfer ratios in normal-appearing white matter on
      conventional MR images of patients with occlusive cerebrovascular disease.
AB  - BACKGROUND AND PURPOSE: Chronic hypoperfusion may cause ischemic insult in the
      deep white matter. The magnetization transfer phenomenon is associated with the
      amount and constitution of myelin. The purpose of this study was to assess the
      usefulness of the magnetization transfer ratio (MTR) for detecting
      vasculometabolic abnormalities on positron emission tomography (PET) studies in
      patients with unilateral severe stenosis of the internal carotid artery (ICA).
      METHODS: MTR maps and PET data-including regional cerebral blood flow (rCBF),
      regional cerebral metabolic rate of oxygen (rCMRO(2)), and regional oxygen
      extraction fraction (rOEF)-were investigated in 13 patients with unilateral
      severe stenosis of the ICA. The same regions of interest were selected in the
      white matter both on MTR maps and PET scans. The areas were classified into three
      groups based on MTR values (group 0, MTR >47.22%; group 1, MTR = 45.77% to
      47.22%; group 2, MTR <45.77%), and the relationship between MTR and PET data was
      analyzed by means of both absolute values and asymmetric index (AI). RESULTS:
      Abnormal values could not be detected in the areas classified as group 0. The
      areas classified as group 1 were characterized by absolutely normal values of
      rCMRO(2) and increased rOEF with AI, which was assessed as viable and reversible
      on the PET study. The areas classified as group 2 showed decreased rCMRO(2) with
      absolute values, which was considered irreversible in PET. A significant overall
      linear correlation was found between MTR and rCMRO(2) values. CONCLUSION: Using
      the MTR technique to classify ischemic damage into three groups (normal,
      reversible, and irreversible), we found a significant correlation between the
      reduction of MTR and that of rCMRO(2) in white matter with ICA stenosis. We
      believe that the MTR technique may partly replace PET data in the assessment of
      ischemic injury.

PMID- 11337339
TI  - Correlation of cerebrovascular reserve as measured by acetazolamide-challenged
      SPECT with angiographic flow patterns and intra- or extracranial arterial
      stenosis.
AB  - BACKGROUND AND PURPOSE: The ability to identify patients at increased risk for
      stroke from cerebral hemodynamic ischemia may help guide treatment planning. We
      tested the correlation between regional cerebrovascular reserve (rCVR) on
      acetazolamide-challenged single-photon emission CT (SPECT) brain scans and
      intracranial collateral pathways as well as extra- or intracranial (EC-IC)
      arterial stenosis on cerebral angiography. METHODS: A retrospective analysis of
      27 patients who underwent cerebral angiography and acetazolamide-challenged SPECT
      brain imaging was performed. With cerebral angiography, the anterior, middle, and
      posterior cerebral artery (ACA, MCA, PCA) territories were evaluated for patterns
      of flow, including the ipsilateral carotid or basilar arteries, the circle of
      Willis collaterals, the EC-IC collaterals, and the leptomeningeal collaterals.
      With acetazolamide-challenged SPECT, the ACA, MCA, and PCA territories were
      classified as either showing or not showing evidence of decreased rCVR.
      Statistical significance was determined by the chi(2) test. RESULTS: Patients
      with decreased rCVR had significantly greater dependence on either the EC-IC or
      leptomeningeal collaterals (42%) than did patients without decreased rCVR (7%).
      Similarly, the cerebral hemispheres with decreased rCVR showed a higher
      prevalence of 70% or greater stenosis or occlusion of the ipsilateral EC-IC
      arteries in the anterior circulation (74%) than did hemispheres with no evidence
      of decreased rCVR (16%), and this difference was also statistically significant.
      CONCLUSION: Acetazolamide-challenged SPECT brain scanning provides additional
      information regarding rCVR that is not reliably provided by cerebral angiography.

PMID- 11337340
TI  - Comparative analysis of MR imaging, positron emission tomography, and ictal
      single-photon emission CT in patients with neocortical epilepsy.
AB  - BACKGROUND AND PURPOSE: MR imaging, positron emission tomography (PET), and
      single-photon emission CT (SPECT) play important roles in presurgical
      localization of epileptic foci. However, comparative study of these imaging
      methods for cases of neocortical epilepsy has been limited. The purpose of this
      study was to compare the sensitivities of these three imaging methods for
      presurgical localization of neocortical epileptogenic foci. METHODS: We studied
      117 consecutive patients who underwent surgery for intractable neocortical
      epilepsy. The pathologic substrates were neuronal migration disorder (n = 77),
      tumor (n = 15), and others (n = 25). MR imaging was compared retrospectively with
      (18)F-fluorodeoxyglucose PET and ictal technetium-99m hexamethylpropyleneamine
      oxime SPECT regarding their capability to correctly localize the epileptogenic
      foci. The pathologic findings were used as the standard of reference. RESULTS:
      Overall, MR imaging, PET, and ictal SPECT correctly localized the lesions for
      59.8%, 77.7%, and 70.3% of the patients, respectively, with a 38% concordance
      rate among the three methods. PET was most sensitive (71-100%) in detecting all
      substrates. MR imaging was as sensitive (100%) as PET in detecting tumor but was
      least sensitive (48.1%) in detecting neuronal migration disorder. Ictal SPECT was
      more sensitive (75.8%) than MR imaging in detecting neuronal migration disorder.
      Patients with imaging abnormalities achieved good outcomes in 81.4% of the cases,
      in contrast to 59.5% for those without imaging abnormalities (P <.05).
      CONCLUSION: PET and ictal SPECT were overall more sensitive than was MR imaging,
      despite the low concordance rate and variable sensitivity depending on
      substrates. The detection of abnormalities by MR imaging was associated with good
      outcome. PET or ictal SPECT can be well used as complementary tools, particularly
      in cases of negative MR imaging findings.

PMID- 11337341
TI  - Magnetization transfer imaging in patients with clinically isolated syndromes
      suggestive of multiple sclerosis.
AB  - BACKGROUND AND PURPOSE: In patients with multiple sclerosis (MS), reduced
      magnetization transfer ratios (MTRs) have been reported in white matter that
      appears normal on studies obtained with conventional imaging techniques. The
      stage in the disease when this first becomes detectable is unclear. The purpose
      of this study was to measure the MTR of normal-appearing white matter (NAWM) and
      lesions in patients with clinically isolated syndromes (CIS), many of whom are at
      the earliest stages of MS, and to determine the prognostic value of any observed
      changes. METHODS: Twenty-seven CIS patients and 13 matched control subjects were
      studied. The mean MTR was measured from 10 regions of NAWM and, when present,
      from lesions. The patients were followed-up clinically for a median of 12 months.
      RESULTS: There was no significant difference in the mean MTR between NAWM in
      control subjects (38.5% units) and that in CIS patients (38.4% units). After 12
      months' follow-up, MS developed in 26% of the patients. The MTR of NAWM in these
      patients did not differ from that of the other patients or the control subjects.
      CONCLUSION: The reduced MTR in NAWM, described in established MS, was not
      detectable in patients with CIS. MTR did not provide prognostic information for
      this short period of follow-up.

PMID- 11337342
TI  - Mean diffusivity and fractional anisotropy histograms of patients with multiple
      sclerosis.
AB  - BACKGROUND AND PURPOSE: Compared with conventional T2-weighted MR imaging,
      diffusion tensor MR imaging provides quantitative indices with increased
      specificity to the most destructive aspects of multiple sclerosis. In this study,
      we obtained brain mean diffusivity (_D) and fractional anisotropy histograms of
      patients with multiple sclerosis to compare them with those of healthy volunteers
      and to investigate the correlation between diffusion tensor MR imaging histogram
      derived measures and the level of disability and quantities derived from
      conventional MR imaging. METHODS: Dual-echo and diffusion tensor MR images were
      obtained from 78 patients with relapsing-remitting, secondary progressive, or
      primary progressive multiple sclerosis and from 20 healthy control volunteers.
      After obtaining mean diffusivity (_D) and fractional anisotropy images and image
      coregistration, _D and fractional anisotropy histograms were created. From each
      histogram, the following measures were derived: the average _D and fractional
      anisotropy, the histogram peak heights, and the histogram peak locations.
      RESULTS: All the _D and fractional anisotropy histogram-derived measures were
      different between patients and controls at a significance level of P <.001. No
      differences were found in any of the considered quantities among the three
      multiple sclerosis phenotypes. In patients with relapsing-remitting multiple
      sclerosis, disability was correlated with histogram average_D (r = 0.4, P =.01)
      and peak height (r = -0.4, P =.01). In patients with secondary progressive
      multiple sclerosis, disability was correlated with fractional anisotropy
      histogram peak position (r = -0.6, P =.01). Significant correlations were also
      found between T2 lesion load and various diffusion tensor MR quantities.
      CONCLUSION: This study shows that brain _D and fractional anisotropy histograms
      are different for patients with multiple sclerosis compared with control
      volunteers. This study also shows that quantities derived from diffusion tensor
      MR imaging are correlated with disability in patients with relapsing-remitting
      multiple sclerosis and secondary progressive multiple sclerosis, suggesting that
      they might serve as additional measures of outcome when monitoring multiple
      sclerosis evolution in these patients.

PMID- 11337343
TI  - Preliminary assessment of turbo spectroscopic imaging for targeting in brain
      biopsy.
AB  - BACKGROUND AND PURPOSE: Brain biopsy remains an integral and necessary component
      in the diagnosis of brain lesions. We assessed the ability of turbo spectroscopic
      imaging (TSI) to provide a physiologically based target for tissue sampling.
      METHODS: TSI was performed in 26 anesthetized patients immediately before MR
      guided brain biopsy. In 10 patients, single-voxel spectroscopy was performed on
      the TSI-indicated target and correlated with the TSI findings. Biopsy samples
      were taken from the imaging and spectroscopically defined target(s) under MR
      guidance, and pathologic findings were compared with preoperative spectra.
      RESULTS: TSI alone provided a definitive target based on a region of elevated
      choline in 17 of 21 patients in whom a neoplasm was confirmed. The remaining four
      neoplasms exhibited relatively low metabolic levels and were difficult to
      distinguish from the five cases of radiation necrosis seen in this study. TSI
      findings were in qualitative agreement with those obtained at single-voxel
      spectroscopy, although TSI spectra exhibited more contamination. Quantitative
      spectral analysis of TSI data is limited by low spectral resolution. CONCLUSION:
      TSI is helpful for determining an appropriate biopsy target in heterogeneous
      lesions. Coupling TSI targeting with conventional imaging and intraoperative
      confirmation of needle positioning resulted in a 100% diagnostic success rate and
      increased the clinician's confidence in the histologic findings.

PMID- 11337344
TI  - Diffusion-weighted MR imaging of intracerebral masses: comparison with
      conventional MR imaging and histologic findings.
AB  - BACKGROUND AND PURPOSE: The purposes of this study were to find the role of
      diffusion-weighted MR imaging in characterizing intracerebral masses and to find
      a correlation, if any, between the different parameters of diffusion-weighted
      imaging and histologic analysis of tumors. The usefulness of diffusion-weighted
      imaging and apparent diffusion coefficient (ADC) maps in tumor delineation was
      evaluated. Contrast with white matter and ADC values for tumor components with
      available histology were also evaluated. METHODS: Twenty patients with clinical
      and routine MR imaging/CT evidence of intracerebral neoplasm were examined with
      routine MR imaging and echo-planar diffusion-weighted imaging. The routine MR
      imaging included at least the axial T2-weighted fast spin-echo and axial T1
      weighted spin-echo sequences before and after contrast enhancement. The diffusion
      weighted imaging included an echo-planar spin-echo sequence with three b values
      (0, 300, and 1200 s/mm(2)), sensitizing gradient in the z direction, and
      calculated ADC maps. The visual comparison of routine MR images with diffusion
      weighted images for tumor delineation was performed as was the statistical
      analysis of quantitative diffusion-weighted imaging parameters with histologic
      evaluation. RESULTS: For tumors, the diffusion-weighted images and ADC maps of
      gliomas were less useful than the T2-weighted spin-echo and contrast-enhanced T1
      weighted spin-echo images in definition of tumor boundaries. Additionally, in six
      cases of gliomas, neither T2-weighted spin-echo nor diffusion-weighted images
      were able to show a boundary between tumor and edema, which was present on
      contrast-enhanced T1-weighted and/or perfusion echo-planar images. The ADC values
      of solid gliomas, metastases, and meningioma were in the same range. In two cases
      of lymphomas, there was a good contrast with white matter, with strongly reduced
      ADC values. For infection, the highest contrast on diffusion-weighted images and
      lowest ADC values were observed in association with inflammatory granuloma and
      abscess. CONCLUSION: Contrary to the findings of previous studies, we found no
      clear advantage of diffusion-weighted echo-planar imaging in the evaluation of
      tumor extension. The contrast between gliomas, metastases, meningioma, and white
      matter was generally lower on diffusion-weighted images and ADC maps compared
      with conventional MR imaging. Unlike gliomas, the two cases of lymphomas showed
      hyperintense signal on diffusion-weighted images whereas the case of cerebral
      abscess showed the highest contrast on diffusion-weighted images with very low
      ADC values. Further study is required to find out whether this may be useful in
      the differentiation of gliomas and metastasis from lymphoma and abscess.

PMID- 11337345
TI  - Initial and follow-up MR imaging findings in AIDS-related progressive multifocal
      leukoencephalopathy treated with highly active antiretroviral therapy.
AB  - BACKGROUND AND PURPOSE: Recent studies have shown the beneficial effect of highly
      active antiretroviral therapy (HAART) in AIDS-related progressive multifocal
      leukoencephalopathy (PML). The purpose of our study was to evaluate the initial
      and follow-up imaging findings and survival in patients with PML who were treated
      with HAART. METHODS: The clinical course and MR imaging findings on initial and
      follow-up MR studies in four consecutive AIDS patients with PML who were treated
      with HAART are described. RESULTS: Two patients were short-term survivors and
      died after 3 months. Two patients are still alive, with a survival time of 22 and
      43 months, respectively. On initial MR studies, more extensive white matter
      changes were seen in the short-term survivors. Development of a mass effect and
      temporary enhancement (in one patient) was observed in two HAART responders on
      follow-up MR studies. Increased hypointensity on T1-weighted images with
      concomitant low signal on fluid-attenuated inversion-recovery fast spin-echo
      (FLAIR-FSE) images was seen in two responders, representing leukomalacia.
      Atrophic changes of the involved areas of the brain, consistent with burnt out
      PML lesions, were seen in two long-term survivors. In the short-term survivors,
      increased hypointensity was present on T1-weighted images with increased high
      signal on FLAIR-FSE images, representing progressive destructive disease.
      CONCLUSION: Our results suggest that a clinical and radiologic response can be
      seen in some patients with AIDS-associated PML on HAART while in others there may
      be no beneficial response. Development of a mass effect and temporary enhancement
      on MR images in the early phase of treatment might represent positive predictive
      factors for prolonged survival.

PMID- 11337346
TI  - Method for quantitatively evaluating the lateralization of linguistic function
      using functional MR imaging.
AB  - BACKGROUND AND PURPOSE: Various methods for evaluating the lateralization of
      linguistic function using functional MR imaging have been proposed. However, the
      optimal method remains controversial. The purpose of this study was not only to
      establish a method for quantitatively evaluating the lateralization of linguistic
      function but also to evaluate its optimality. METHODS: Internal speech tasks were
      measured by functional MR imaging in 17 healthy adult volunteers by use of z
      scores. The laterality index (LI) was calculated first by a previously reported
      method and second by our newly designed method, in which we investigated the
      correlation between the z scores and the number of activated pixels in the
      regions of interest; that is, we made scatter diagrams (z scores versus number of
      activated pixels). To obtain detailed information, we searched a regression
      function that fit the scatter diagrams well. RESULTS: We found the number of
      activated pixels was proportional to (1/z score)(4) and the correlation
      coefficient was very high. Each hemisphere showed an original proportional
      constant. Our newly designed LI was calculated from these two constants and was
      found to be a fixed value. In contrast, the reported LI varied with the z score.
      We found our LI differed in robustness and reproducibility from the reported LI.
      CONCLUSION: Our LI method proved more optimal than the reported LI. The
      lateralization of linguistic function can be evaluated quantitatively using our
      new LI method.

PMID- 11337347
TI  - Spontaneous closure of dural arteriovenous fistulas: report of three cases and
      review of the literature.
AB  - SUMMARY: Three cases of spontaneously closing dural arteriovenous fistulas (AVFs)
      are presented, and 11 previously published cases are reviewed. On the basis of
      clinical and angiographic data, two types of spontaneously regressing dural AVFs
      are distinguished: posttraumatic and spontaneous. In all cases, the explanation
      for spontaneous closure is unknown. Some authors have hypothesized that the
      thrombosis of the draining sinus could be involved. We report three cases of
      spontaneous dural AVF closure with conservation of sinus patency.

PMID- 11337348
TI  - Spinal metastases from renal cell carcinoma: effect of preoperative particle
      embolization on intraoperative blood loss.
AB  - BACKGROUND AND PURPOSE: Surgical repair of spinal metastases from renal origin is
      often complicated by excessive bleeding. The purpose of this study was to assess
      the effect of preoperative particulate embolization on intraoperative blood loss.
      METHODS: Twenty spinal metastases from renal origin (17 patients) treated by
      preoperative embolization with polyvinyl alcohol particles were analyzed
      retrospectively. Surgical decompression was performed within 2 days after
      embolization. A control group of 10 patients with 11 spinal metastases of renal
      origin underwent surgery without embolization. The effect of preoperative
      embolization, of completeness of embolization, and of particle size on the
      estimated intraoperative blood loss was analyzed using nonparametric statistical
      tests. RESULTS: Complete embolization was achieved in 10 cases and partial
      embolization in the other 10. The estimated blood loss of 19 embolized and 11
      control cases was available from the surgical report. Median intraoperative blood
      loss in 19 embolized lesions was 1500 mL (range, 300-8000 mL), compared with 5000
      mL (range, 1440-15000 mL) in the control group. Even after partial embolization,
      blood loss (median, 2000 mL) was significantly lower than in the control group.
      No significant differences in estimated blood loss were noted between the use of
      particles smaller than 250 microm and those larger than 250 microm. No
      embolization-related permanent neurologic deficit or skin or muscle necrosis
      occurred. CONCLUSION: Preoperative embolization of spinal metastases of renal
      origin with polyvinyl alcohol particles is safe and might reduce intraoperative
      blood loss significantly. Even partial embolization seems to be effective.

PMID- 11337349
TI  - An unusual spinal presentation of Whipple disease.
AB  - SUMMARY: When Whipple disease (WD) is confined to the CNS, diagnosis may be
      difficult. We report a case of WD with spinal presentation in an otherwise
      healthy woman who had a 5-year history of relapsing-remitting cervico-thoracic
      myelopathy. We suggest that the diagnosis of WD should be considered in the
      presence of an enlarged and enhancing spinal cord even in the absence of any
      systemic involvement.

PMID- 11337350
TI  - Historical perspective. Electrothrombosis of saccular aneurysms via endovascular
      approach: part 1 and part 2.

PMID- 11337351
TI  - Loss of heterozygosity or intragenic mutation, which comes first?

PMID- 11337352
TI  - Cytokine regulation of gap junction connectivity: an open-and-shut case or
      changing partners at the Nexus?

PMID- 11337353
TI  - Matrix gene expression analysis and cellular phenotyping in chordoma reveals
      focal differentiation pattern of neoplastic cells mimicking nucleus pulposus
      development.
AB  - Chordoma is the fourth most common malignant primary neoplasm of the skeleton and
      almost the only one showing a real epithelial phenotype. Besides classic
      chordoma, so-called chondroid chordoma was described as a specific entity showing
      cartilage-like tissue within chordomatoid structures. However, since its first
      description, strongly conflicting results have been reported about the existence
      of chondroid chordoma and several studies suggested chondroid chordomas being in
      fact low-grade conventional chondrosarcomas. In the present study, we used
      cytoprotein expression profiling and molecular in situ localization techniques of
      marker gene products indicative of developmental phenotypes of chondrocytes to
      elucidate origin and biology of chondroid chordoma. We were able to demonstrate
      the chondrogenic potential of chordomas irrespectively of the appearance of overt
      cartilage formation by identifying the multifocal expression of type II collagen,
      the main marker of chondrocytic differentiation. Additionally, the cartilage
      typical large aggregating proteoglycan aggrecan was present throughout all
      chordomas and, thus, a very characteristic gene product and marker of these
      neoplasms. Biochemical matrix composition and cell differentiation pattern
      analysis showed a high resemblance of classic chordomas and in chordoid areas of
      chondroid chordomas to the fetal chorda dorsalis, whereas chondroid areas of
      chondroid chordomas showed features similar to adult nucleus pulposus. This
      demonstrates on the cell function level the chondrocytic differentiation
      potential of neoplastic chordoid cells as a characteristic facet of chordomas,
      mimicking fetal vertebral development, ie, the transition of the chorda dorsalis
      to the nucleus pulposus. Our study firmly establishes a focal real chondrocytic
      phenotype of neoplastic cells in chordomas. Chondroid chordoma is neither a low
      grade chondrosarcoma nor a misnomer as discussed previously.

PMID- 11337354
TI  - In vivo elimination of acentric double minutes containing amplified MYCN from
      neuroblastoma tumor cells through the formation of micronuclei.
AB  - Neuroblastoma, the most common solid extracranial neoplasm in children, shows an
      appreciable variability in clinical evolution. Amplification of the MYCN oncogene
      in this tumor is detected in 25 to 30% of cases and is associated with poor
      clinical outcome. In this study, quantitative polymerase chain reaction and
      fluorescence in situ hybridization were used to determine MYCN amplification
      status in 46 neuroblastoma tumors. MYCN amplification was detected in tumors from
      11 patients. Fluorescence in situ hybridization revealed the presence of
      micronuclei containing amplified MYCN sequences in 8 of the 11 tumors.
      Micronuclei are indicative of spontaneous elimination or loss of amplified
      sequences by tumor cells. Because the elimination of amplified sequences can be
      enhanced in vitro by specific drugs such as hydroxyurea, our observations suggest
      a new therapeutic strategy specifically targeted to cells with amplified genes.

PMID- 11337355
TI  - FE65 in Alzheimer's disease: neuronal distribution and association with
      neurofibrillary tangles.
AB  - FE65, a protein expressed in the nervous system, has the ability to bind the C
      terminal domain of the amyloid precursor protein. This suggests a role for FE65
      in the pathogenesis of Alzheimer's disease (AD). The present study was conducted
      to find out if the distribution of FE65 immunoreactivity was affected during the
      course of AD, and to determine the degree of co-localization of FE65 with other
      proteins known to be involved in AD. Single immunoperoxidase-labeling
      experiments, conducted on six sporadic AD patients and six nondemented age
      matched controls, showed that the proportion of volume occupied by FE65
      immunoreactivity was not modified in the isocortex of AD patients. However, in
      hippocampal area CA4, increased FE65 immunoreactivity seemed to be associated
      with the severity of the disease. Double-immunofluorescent labeling did not show
      any clear co-localization of FE65 with the amyloid precursor protein. FE65
      immunoreactivity was also absent from focal and diffuse deposits of the beta
      amyloid peptide. Unexpectedly double labeling experiments showed a co
      localization of FE65 and tau proteins in intracellular tangles. Ultrastructural
      observations confirmed that FE65 was associated with paired helical filaments.

PMID- 11337356
TI  - Differential expression of cytotoxic molecules and killer cell inhibitory
      receptors in CD8+ and CD56+ cutaneous lymphomas.
AB  - Cutaneous lymphomas of the cytotoxic phenotype, including CD8+ and CD56+
      lymphomas, have only recently been recognized. To characterize the phenotypic
      profile of these lymphomas, we investigated the expression of both cytotoxic
      molecules and killer cell inhibitory receptors by immunohistochemistry
      techniques. Frozen sections from four CD8+ and from three CD56+ cutaneous
      lymphomas were stained for the cytotoxicity markers including T-cell restricted
      intracellular antigen-1, perforin, granzyme B, and for expression of the
      inhibitory receptors including p58.1, p58.2, p70, p140, CD94, NKG2, and leukocyte
      immunoglobulin-like receptor (LIR-1). Apart from LIR-1, the CD8+ lymphomas in our
      series express p70 and p140 from the inhibitory receptors and only one or two of
      the cytotoxic proteins. The CD56+ lymphomas, on the other hand, express only LIR
      1 of the set of inhibitory receptors and the whole panel of cytotoxic antigens.
      Various subtypes of cytotoxic cutaneous lymphomas (CD8+ and CD56+) differ in
      regard to their phenotypic and functional profile, which may explain differences
      in their biological behavior.

PMID- 11337357
TI  - Translocation T(4;14)(p16.3;q32) is a recurrent genetic lesion in primary
      amyloidosis.
AB  - Primary amyloidosis is a fatal disorder characterized by low numbers of clonal
      plasma cells in the bone marrow and the systemic deposition of light chain
      fragments in the form of amyloid. The molecular pathobiology of amyloidosis is
      primarily unknown. Recently, a novel karyotypically undetectable
      t(4;14)(p16.3;q32) translocation has been identified in approximately 20% of
      multiple myeloma patients. The translocation leads to the apparent deregulation
      of two genes located on 4p16.3, the fibroblast growth-factor receptor 3 (FGFR3),
      and the putative transcription factor multiple myeloma SET domain (MMSET), and to
      the generation of IGH/MMSET hybrid transcripts. In this study, we investigated
      the presence of the t(4;14) translocation in 42 AL patients using a reverse
      transcriptase-polymerase chain reaction assay for the detection of IGH/MMSET
      transcripts. Chimeric transcripts were found in six patients (14%) and were
      consistent with a 4p16.3 breakpoint involving intron 3 and juxtaposing IGH
      regions to exon 4. In three of these cases, hybrid transcripts juxtaposing IGH
      regions to exon 5 were also observed and were probably the result of an
      alternative splicing skipping exon 4. Because all of the fusion transcripts (six
      of six) excluded exon 3, the first translated MMSET exon, only putative 5'
      truncated MMSET proteins could be generated. In conclusion, our results
      demonstrate that the t(4;14)(p16.3;q32) translocation is a recurrent genetic
      lesion in primary amyloidosis.

PMID- 11337358
TI  - Polycystic kidney rat is a novel animal model of Caroli's disease associated with
      congenital hepatic fibrosis.
AB  - Caroli's disease (congenital intrahepatic biliary dilatation) associated with
      congenital hepatic fibrosis is an autosomal recessive polycystic kidney disease.
      Recently, the polycystic kidney (PCK) rat, a spontaneous mutant derived from a
      colony of CRJ:CD rats with polycystic lesions in the liver and an autosomal
      recessive mode of inheritance, was reported. In the present study, the pathology
      of the hepatobiliary system and the biliary cell-kinetics were evaluated in
      fetuses (day 18 to 21 of gestation) and neonates and adults (1 day to 4 months
      after delivery) of PCK rats. CRJ:CD rats were used as a control. Multiple
      segmental and saccular dilatations of intrahepatic bile ducts were first observed
      in fetuses at 19 days of gestation. The dilatation spread throughout the liver
      and the degree of dilatation increased with aging. Gross and histological
      features characterizing ductal plate malformation were common in the intrahepatic
      bile ducts. Overgrowth of portal connective tissue was evident and progressive
      after delivery. These features were very similar to those of Caroli's disease
      with congenital hepatic fibrosis. Proliferative activity in the biliary
      epithelial cells was greater in PCK rats than controls during the development. In
      contrast, the biliary epithelial apoptosis was less extensive in PCK rats than
      the controls until 1 week after delivery, but greater after 3 weeks, suggesting
      that the remodeling defect in immature bile ducts associated with the imbalance
      of cell kinetics plays a role in the occurrence of intrahepatic biliary anomalies
      in PCK rats. The PCK rat could be a useful and promising animal model of Caroli's
      disease with congenital hepatic fibrosis.

PMID- 11337359
TI  - Laser-induced noninvasive vascular injury models in mice generate platelet- and
      coagulation-dependent thrombi.
AB  - A minimally invasive laser-induced injury model is described to study thrombus
      development in mice in vivo. The protocol involves focusing the beam of an argon
      ion laser through a compound microscope on the vasculature of a mouse ear that is
      sufficiently thin such that blood flow can be visualized by intravital
      microscopy. Two distinct injury models have been established. The first involves
      direct laser illumination with a short, high-intensity pulse. In this case,
      thrombus formation is inhibited by the GPIIb/IIIa antagonist, G4120. However, the
      anticoagulants, hirulog, PPACK, and NapC2 have minimal effect. This indicates
      that thrombus development induced by this model mainly involves platelet
      interactions. The second model involves low-intensity laser illumination of mice
      injected with Rose Bengal dye to induce photochemical injury in the region of
      laser illumination. Thrombi generated by this latter procedure have a slower
      development and are inhibited by both anticoagulant and anti-platelet compounds.

PMID- 11337360
TI  - Degenerate oligonucleotide primed-polymerase chain reaction-based array
      comparative genomic hybridization for extensive amplicon profiling of breast
      cancers : a new approach for the molecular analysis of paraffin-embedded cancer
      tissue.
AB  - We have developed a protocol for degenerate oligonucleotide-primed-polymerase
      chain reaction-based array comparative genomic hybridization (array CGH) that,
      when combined with a laser microdissection technique, allows the analysis of
      cancer cell populations isolated from routine, formalin-fixed, paraffin-embedded
      tissue samples. Comparison of copy number changes detected by degenerate
      oligonucleotide-primed-polymerase chain reaction-based array CGH to those
      detected by conventional array CGH or fluorescence in situ hybridization,
      demonstrated that amplifications can be reliably detected. Using a genomic
      microarray containing 57 oncogenes, we screened a total of 28 breast cancer
      samples and obtained a detailed amplicon profile that is the most comprehensive
      to date in human breast cancer. The array CGH method described here will allow
      the genetic analysis of paraffin-embedded human cancer materials for example in
      the context of clinical trials.

PMID- 11337361
TI  - Differences between squamous cell carcinoma and keratoacanthoma in angiotensin
      type-1 receptor expression.
AB  - Angiotensin II receptors are the specific receptors of angiotensin II of the
      renin-angiotensin system. The existence and role of the receptors in the skin
      have not been determined. We immunohistochemically studied the expression of
      angiotensin receptors in the human skin. The results demonstrated the expression
      of angiotensin type 1 receptor (AT1) in the normal human suprabasal epidermis.
      The expression pattern suggests the role of AT1 in association with
      differentiation. In addition, we studied the expression of AT1 in squamous cell
      carcinoma (SCC) of the skin, SCC of the lip, and keratoacanthoma (KA). Our
      experiments showed that high, intermediate, and low levels of AT1 were observed
      in 37 (74.0%), 7 (14.0%), and 2 (4.0%) of 50 cases of SCC of the skin,
      respectively, and the negative periphery pattern was observed in 17 (77.3%) of 22
      cases of KA. These observations suggest that the immunohistochemical study of AT1
      is useful to distinguish SCC from KA. Studying the role and distribution of AT1
      may help in understanding the pathophysiology of the skin.

PMID- 11337362
TI  - Expression profiling of renal epithelial neoplasms: a method for tumor
      classification and discovery of diagnostic molecular markers.
AB  - The expression patterns of 7075 genes were analyzed in four conventional (clear
      cell) renal cell carcinomas (RCC), one chromophobe RCC, and two oncocytomas using
      cDNA microarrays. Expression profiles were compared among tumors using various
      clustering algorithms, thereby separating the tumors into two categories
      consistent with corresponding histopathological diagnoses. Specifically,
      conventional RCCs were distinguished from chromophobe RCC/oncocytomas based on
      large-scale gene expression patterns. Chromophobe RCC/oncocytomas displayed
      similar expression profiles, including genes involved with oxidative
      phosphorylation and genes expressed normally by distal nephron, consistent with
      the mitochondrion-rich morphology of these tumors and the theory that both
      lesions are related histogenetically to distal nephron epithelium. Conventional
      RCCs underexpressed mitochondrial and distal nephron genes, and were further
      distinguished from chromophobe RCC/oncocytomas by overexpression of vimentin and
      class II major histocompatibility complex-related molecules. Novel, tumor
      specific expression of four genes-vimentin, class II major histocompatibility
      complex-associated invariant chain (CD74), parvalbumin, and galectin-3-was
      confirmed in an independent tumor series by immunohistochemistry. Vimentin was a
      sensitive, specific marker for conventional RCCs, and parvalbumin was detected
      primarily in chromophobe RCC/oncocytomas. In conclusion, histopathological
      subtypes of renal epithelial neoplasia were characterized by distinct patterns of
      gene expression. Expression patterns were useful for identifying novel molecular
      markers with potential diagnostic utility.

PMID- 11337363
TI  - Increased glomerular and tubular expression of transforming growth factor-beta1,
      its type II receptor, and activation of the Smad signaling pathway in the db/db
      mouse.
AB  - Activation of the renal transforming growth factor-beta (TGF-beta) system likely
      mediates the excess production of extracellular matrix in the diabetic kidney. To
      establish the role of the TGF-beta system in type 2 diabetic nephropathy, we
      examined the intrarenal localization and expression of the TGF-beta1 isoform, the
      TGF-beta type II receptor, and the Smad signaling pathway in the 16-week-old
      db/db mouse, a genetic model of type 2 diabetes that exhibits mesangial matrix
      expansion, glomerular basement membrane thickening, and renal insufficiency that
      closely resemble the human disease. Compared with its nondiabetic db/m
      littermate, the db/db mouse showed significantly increased TGF-beta1 mRNA
      expression by in situ hybridization in both glomerular and tubular compartments.
      Likewise, TGF-beta1 protein, by immunohistochemical staining, was increased in
      both renal compartments, but the fractional expression of TGF-beta1 protein was
      less than that of the mRNA in the glomerulus. In situ hybridization and
      immunohistochemical staining for the TGF-beta type II receptor revealed
      concordant and significant increases of both mRNA and protein in the glomerular
      and tubular compartments of diabetic animals. Finally, immunohistochemistry
      showed preferential accumulation of Smad3 in the nuclei of glomerular and tubular
      cells in diabetes. The complementary technique of Southwestern histochemistry
      using a labeled Smad-binding element demonstrated increased binding of nuclear
      proteins to Smad-binding element, indicating active signaling downstream of the
      TGF-beta stimulus. We therefore propose that the TGF-beta system is up-regulated
      at the ligand, receptor, and signaling levels throughout the renal cortex in this
      animal model of type 2 diabetes. Our findings suggest that the profibrotic
      effects of TGF-beta may underlie the progression to glomerulosclerosis and
      tubulointerstitial fibrosis that characterize diabetic nephropathy.

PMID- 11337364
TI  - Expression and localization of a novel Rab small G protein (Rab38) in the rat
      lung.
AB  - The Rab small G protein family participates in intracellular vesicle transport,
      including exocytosis and endocytosis. The cDNA encoding a novel Rab-related small
      G protein (Rab38) has been cloned from rat lung cDNA library and recorded in
      GenBank (accession no. M94043). However, the expression and localization of the
      protein in the lung remains primarily unknown. We produced polyhistidine-tagged
      recombinant Rab38 and a polyclonal antibody with a synthetic peptide.
      Immunohistochemistry demonstrated that the protein is specifically localized in
      alveolar type II cells and in bronchial epithelial cells. In situ hybridization
      using a digoxygenin-labeled RNA riboprobe clearly showed that the mRNA of the
      protein is localized in alveolar type II cells and bronchial epithelial cells,
      especially terminal airway epithelial cells. Western blot and reverse
      transcriptase-polymerase chain reaction showed distinct expression of the protein
      and mRNA in isolated alveolar type II cells, but not in alveolar macrophages. The
      native protein was predominantly hydrophobic and was enriched in a high-density
      vesicle fraction but was barely detectable in nuclear and lamellar body fractions
      in alveolar type II cells. Immunofluorescence cytochemistry performed on cultured
      alveolar type II cells showed that Rab38 distributed extensively in the cytoplasm
      with a distribution pattern similar to endoplasmic reticulum rather than other
      subcellular organelles. These results suggest that this novel rab small G protein
      (Rab38) mediates vesicular transport in terminal airway epithelium.

PMID- 11337365
TI  - Allelic loss is often the first hit in the biallelic inactivation of the p53 and
      DPC4 genes during pancreatic carcinogenesis.
AB  - The presumed precursor lesions of pancreatic ductal adenocarcinoma were recently
      classified according to their increasing grade of dysplasia and were designated
      as pancreatic intraepithelial neoplasia (PanIN) 1 through 3. In this study, we
      tested whether molecular genetic alterations can be correlated with this
      classification and may help to further categorize the various PanIN grades. We
      determined the frequencies of allelic loss at chromosomal arms 9p, 17p, and 18q
      in 81 microdissected duct lesions of various PanIN grades, using a combination of
      whole genome amplification and microsatellite analysis. In addition we examined
      the p53 and Dpc4 protein expression patterns by immunohistochemical analysis. In
      PanIN-1, we did not detect allelic losses. In PanIN-2, allelic losses were found
      in increasing frequency, and were particularly high in those lesions with
      moderate-grade dysplasia (low grade, 20, 33, and 17%, loss at 9p, 17p, and 18q,
      respectively; moderate grade, 46, 77, and 58%). PanIN-3 and invasive carcinomas
      exhibited abundant losses. Abnormal p53 and Dpc4 protein expression was only
      rarely identified in PanIN-2 lesions, but occurred frequently in PanIN-3 lesions
      and invasive carcinomas. The combined genetic and protein expression data support
      a model in which allelic loss is the first hit in the biallelic inactivation of
      the p53 and DPC4 tumor suppressor genes. In addition, our data indicate that
      allelic loss analysis may be useful in separating PanIN-2 lesions with low-grade
      dysplasia from those PanIN-2 lesions with moderate-grade dysplasia, each
      potentially representing a distinct progression step toward invasive carcinoma.

PMID- 11337366
TI  - Expression of a novel RNA-splicing factor, RA301/Tra2beta, in vascular lesions
      and its role in smooth muscle cell proliferation.
AB  - RA301/Tra2beta, a sequence-specific RNA-binding protein, was first cloned as a
      stress molecule in re-oxygenated astrocytes. In human vascular tissues, we have
      found enhanced RA301/Tra2beta expression in coronary artery with intimal
      thickening, and atherosclerotic aorta. Balloon injury to the rat carotid artery
      induced RA301/Tra2beta transcripts followed by expression of the antigen, which
      was detected in medial and neointimal vascular smooth muscle cells (VSMCs). In
      cultured VSMCs, hypoxia/re-oxygenation caused induction of RA301/Tra2beta and was
      accompanied by cell proliferation, both of which were blocked by the addition of
      either diphenyl iodonium, a NADPH oxidase inhibitor, PD98059, a mitogen-activated
      protein kinase kinase inhibitor, or antisense oligonucleotide for RA301/Tra2beta.
      Consistent with a link between RA301/Tra2beta and cell proliferation, platelet
      derived growth factor also induced expression of RA301/Tra2beta in cultured
      VSMCS: These data suggest a possible role for RA301/Tra2beta in the regulation of
      VSMC proliferation, especially in the setting of hypoxia/re-oxygenation-induced
      cell stress.

PMID- 11337367
TI  - Tissue-dependent alteration of protease expression phenotype in murine peritoneal
      mast cells that were genetically labeled with green fluorescent protein.
AB  - The changing process of protease expression phenotype was studied after
      transplantation of peritoneal mast cells (PMCs). To pursue the fate of the
      transplanted PMCs, we obtained PMCs from WBB6F(1)-c-kit(+)/c-kit(+) mice with a
      transgene encoding green fluorescent protein (GFP). A large (n = 10(4)) or small
      (n = 500) number of PMCs was injected into the stomach wall of genetically mast
      cell-deficient WBB6F(1)-c-kit(W)/c-kit(Wv) mice without the GFP transgene. The
      original PMCs expressed messenger (m) RNAs of both mast cell carboxypeptidase A
      (MC-CPA) and mouse mast cell protease (mMCP)-2. The MC-CPA(+)/mMCP-2(+) phenotype
      did not change in both the muscularis propria and mucosa when 10(4) PMCs were
      injected. In contrast, when 500 PMCs were injected, the mast cells that developed
      in the muscularis propria showed MC-CPA(+)/mMCP-2(-) phenotype and those that
      appeared in the mucosa showed MC-CPA(-)/mMCP-2(+) phenotype. On day 1 after the
      injection of 500 PMCs, only approximately 20 GFP(+) cells were detected in the
      muscularis propria and no GFP(+) cells in the mucosa. The proportion of Alcian
      blue(+) cells decreased until day 7 and increased thereafter. The GFP(+) but
      Alcian blue(-) cells were considered as degranulated PMCS: The remarkable
      decrease or degranulation seemed to be necessary for the alteration of protease
      expression phenotype.

PMID- 11337368
TI  - Cxcr3 and its ligand CXCL10 are expressed by inflammatory cells infiltrating lung
      allografts and mediate chemotaxis of T cells at sites of rejection.
AB  - The attraction of T lymphocytes into the pulmonary parenchyma represents an
      essential step in mechanisms ultimately leading to lung allograft rejection. In
      this study we evaluated whether IP-10 (CXCL10), a chemokine that is induced by
      interferon-gamma and stimulates the directional migration of activated T cells,
      plays a role in regulating the trafficking of effector T cells during lung
      allograft rejection episodes. Immunohistochemical examination showed that areas
      characterized by acute cellular rejection (grades 1 to 4) and active obliterative
      bronchiolitis (chronic rejection, Ca) were infiltrated by T cells expressing
      CXCR3, i.e., the specific receptor for CXCL10. In parallel, T cells accumulating
      in the bronchoalveolar lavage of lung transplant recipients with rejection
      episodes were CXCR3+ and exhibited a strong in vitro migratory capability in
      response to CXCL10. In lung biopsies, CXCL10 was abundantly expressed by graft
      infiltrating macrophages and occasionally by epithelial cells. Alveolar
      macrophages expressed and secreted definite levels of CXCL10 capable of inducing
      chemotaxis of the CXCR3+ T-cell line 300-19; the secretory capability of alveolar
      macrophages was up-regulated by preincubation with interferon-gamma.
      Interestingly, striking levels of CXCR3 ligands could be demonstrated in the
      fluid component of the bronchoalveolar lavage in individuals with rejection
      episodes. These data indicate the role of the CXCR3/CXCL10 interactions in the
      recruitment of lymphocytes at sites of lung rejection and provide a rationale for
      the use of agents that block the CXCR3/CXCL10 axis in the treatment of lung
      allograft rejection.

PMID- 11337369
TI  - Human trophoblast invasion and spiral artery transformation: the role of PECAM-1
      in normal pregnancy, preeclampsia, and fetal growth restriction.
AB  - During early human pregnancy extravillous cytotrophoblasts invade the uterus and
      spiral arteries transforming them into large vessels of low resistance. Failure
      of trophoblast invasion and spiral artery transformation occurs in preeclampsia
      and fetal growth restriction (FGR); these processes are not well understood.
      Recent studies have suggested that cytotrophoblasts that invade spiral arteries
      mimic the endothelial cells they replace and express PECAM-1. It was also
      reported that in preeclampsia, cytotrophoblasts fail to express PECAM-1 and that
      failure to express endothelial cell adhesion molecules may account for failed
      trophoblast invasion. Despite the possible importance of adhesion molecules in
      trophoblast invasion, no study has systematically investigated the expression of
      PECAM-1 in the placental bed throughout the period of invasion, particularly in
      the myometrial segments where the key failure occurs. There are no studies on
      PECAM-1 expression in the placental bed in FGR. We have examined the expression
      of PECAM-1 in placental bed biopsies and placentas from 8 to 19 weeks of
      gestation and in the placenta and placental bed in the third trimester in cases
      of preeclampsia, FGR, and control pregnancies. PECAM-1 was expressed on
      endothelium of vessels in the placenta and placental bed but not by villous or
      extravillous trophoblasts in normal or pathological samples. These findings do
      not support a role for PECAM-1 in normal invasion or in the pathophysiology of
      preeclampsia or FGR.

PMID- 11337370
TI  - Nephrin redistribution on podocytes is a potential mechanism for proteinuria in
      patients with primary acquired nephrotic syndrome.
AB  - We investigated the distribution of nephrin by immunofluorescence microscopy in
      renal biopsies of patients with nephrotic syndrome: 13 with membranous
      glomerulonephritis (GN), 10 with minimal change GN, and seven with focal
      segmental glomerulosclerosis. As control, six patients with IgA GN without
      nephrotic syndrome and 10 normal controls were studied. We found an extensive
      loss of staining for nephrin and a shift from a podocyte-staining pattern to a
      granular pattern in patients with nephrotic syndrome, irrespective of the primary
      disease. In membranous GN, nephrin was co-localized with IgG immune deposits. In
      the attempt to explain these results, we investigated in vitro whether stimuli
      acting on the cell cytoskeleton, known to be involved in the pathogenesis of GN,
      may induce redistribution of nephrin on the surface of human cultured podocytes.
      Aggregated but not disaggregated human IgG(4), plasmalemmal insertion of membrane
      attack complex of complement, tumor necrosis factor-alpha, and puromycin, induced
      the shedding of nephrin with a loss of surface expression. This phenomenon was
      abrogated by cytochalasin and sodium azide. These results suggest that the
      activation of cell cytoskeleton may modify surface expression of nephrin allowing
      a dislocation from plasma membrane to an extracellular site.

PMID- 11337371
TI  - A vitamin D analog ameliorates glomerular injury on rat glomerulonephritis.
AB  - OCT (22-oxa-calcitriol), a vitamin D analog, has been reported to show strong
      inhibitory effects on mesangial cell proliferation in vitro. In the present
      study, we report a study of the effect of OCT on anti-thy-1 glomerulonephritis.
      Both OCT and 1,25(OH)(2)D(3) significantly inhibited mesangial cell
      proliferation, the degree of glomerulosclerosis, and albuminuria at day 8
      compared to the disease control group. The OCT-treated group showed normal
      calcium levels but the 1,25(OH)(2)D(3)-treated group showed higher levels. The
      disease control group showed a marked increase of type I and type IV collagens,
      and alpha-smooth muscle actin (alpha-SMA) compared to the normal group. The
      treatment of OCT or 1,25(OH)(2)D(3) significantly reduced the expression of these
      proteins. The mRNA of the glomeruli of anti-thy-1 model expressed significantly
      higher levels of type I and type IV collagens, and alpha-SMA at day 8 compared to
      normal rats. Treatment with OCT or 1,25(OH)(2)D(3) inhibited the mRNA expressions
      of type I and type IV collagens, as well as that of alpha-SMA. These data
      demonstrate that OCT inhibits mesangial cell proliferation and extracellular
      matrix expansion with a low calcemic activity. Disease control rats showed
      significantly increased levels of transforming growth factor-beta1 protein in the
      glomeruli, but treatment with OCT or 1,25(OH)(2)D(3) markedly reduced this
      expression. The levels of mRNA in glomeruli were also consistent with these
      protein levels. Therefore, the suppressive effect of OCT may be mediated by
      inhibition of transforming growth factor-beta1. The present results suggest that
      OCT has potential for use in therapeutic strategy for the treatment of
      glomerulonephritis without inducing hypercalcemia.

PMID- 11337372
TI  - Systemic infusion of angiotensin II into normal rats activates nuclear factor
      kappaB and AP-1 in the kidney: role of AT(1) and AT(2) receptors.
AB  - Recent studies have pointed out the implication of angiotensin II (Ang II) in
      various pathological settings. However, the molecular mechanisms and the AngII
      receptor (AT) subtypes involved are not fully identified. We investigated whether
      AngII elicited the in vivo activation of nuclear transcription factors that play
      important roles in the pathogenesis of renal and vascular injury. Systemic
      infusion of Ang II into normal rats increased renal nuclear factor (NF)-kappaB
      and AP-1 binding activity that was associated with inflammatory cell infiltration
      and tubular damage. Interestingly, infiltrating cells presented activated NF
      kappaB complexes, suggesting the involvement of AngII in inflammatory cell
      activation. When rats were treated with AT(1) or AT(2) receptor antagonists
      different responses were observed. The AT(1) antagonist diminished NF-kappaB
      activity in glomerular and tubular cells and abolished AP-1 in renal cells,
      improved tubular damage and normalized the arterial blood pressure. The AT(2)
      antagonist diminished mononuclear cell infiltration and NF-kappaB activity in
      glomerular and inflammatory cells, without any effect on AP-1 and blood pressure.
      These data suggest that AT(1) mainly mediates tubular injury via AP-1/NF-kappaB,
      whereas AT(2) receptor participates in the inflammatory cell infiltration in the
      kidney by NF-kappaB. Our results provide novel information on AngII receptor
      signaling and support the recent view of Ang II as a proinflammatory modulator.

PMID- 11337373
TI  - Suppression of vascular endothelial growth factor-mediated endothelial cell
      protection by survivin targeting.
AB  - The protective genes that mediate endothelial cell (EC) survival during
      angiogenesis have not been completely characterized. Here, we show that an
      antisense oligonucleotide to the apoptosis inhibitor survivin suppressed de novo
      expression of survivin in ECs by vascular endothelial cell growth factor (VEGF).
      In contrast, the survivin antisense oligonucleotide did not affect anti-apoptotic
      bcl-2 levels in endothelium. When assessed in cell death assays, antisense
      targeting of survivin abolished the anti-apoptotic function of VEGF against tumor
      necrosis factor-alpha- or ceramide-induced cell death, enhanced caspase-3
      activity, promoted the generation of a approximately 17-kd active caspase-3
      subunit, and increased cleavage of the caspase substrate, polyADP ribose
      polymerase. In contrast, the survivin antisense oligonucleotide had no effect on
      EC viability in the absence of VEGF. Antisense oligonucleotides to platelet
      endothelial cell adhesion molecule-1 (PECAM-1, CD31), lymphocyte function
      associated molecule-3 (LFA-3, CD58), or intercellular adhesion molecule-1 (ICAM
      1, CD54) did not reduce the anti-apoptotic function of VEGF in endothelium. When
      tested on other angiogenic activities mediated by VEGF, survivin antisense
      treatment induced rapid regression of three-dimensional vascular capillary
      networks, but did not affect EC migration/chemotaxis. These data suggest that the
      anti-apoptotic properties of VEGF during angiogenesis are primarily mediated by
      the induced expression of survivin in ECS: Manipulation of this pathway may
      increase EC viability in compensatory angiogenesis or facilitate EC apoptosis and
      promote vascular regression during tumor angiogenesis.

PMID- 11337374
TI  - Postatrophic hyperplasia of the prostate gland: neoplastic precursor or innocent
      bystander?
AB  - Postatrophic hyperplasia (PAH) of the prostate gland often demonstrates
      overlapping histological features with prostatic adenocarcinoma (PCA). These
      features include small acinar growth and enlarged nuclei with prominent nucleoli.
      Recent work has demonstrated that PAH is a proliferative, noninvoluting lesion.
      PAH is also histologically distinct from simple atrophy (SA), which has
      intermediate- to large-sized glands, minimal cytoplasm, and inconspicuous nuclei.
      However, despite overlapping features between PAH and PCA, high-grade prostatic
      intraepithelial neoplasm (HGPIN) is still considered the only direct neoplastic
      precursor to PCA. HGPIN resembles PCA in its topographic distribution,
      cytological appearance, and molecular alterations including chromosome 8p loss
      and chromosome 8 centromeric gain. To examine the hypothesis that PAH is the
      earliest histologically distinct precursor to HGPIN or PCA, the frequency,
      distribution, proliferative state, and chromosome 8 gain of benign prostate, SA,
      PAH, HGPIN, and PCA were analyzed. Forty radical prostatectomy specimens from men
      with clinically localized PCA were systematically analyzed. Proliferation was
      determined by Ki-67 immunohistochemistry (MIB-1) on formalin-fixed, paraffin
      embedded tissue and quantified by digital image analysis from a total of 5,510
      sample areas with benign, SA, PAH, HGPIN, and PCA. A tissue microarray was
      constructed to evaluate 8c gain using interphase fluorescence in situ
      hybridization. SA foci (n = 129) and PAH foci (n = 114) were identified in the 40
      cases of which 74% (95 of 129) and 88% (100 of 114) were seen in the peripheral
      zone, respectively (P = 0.006). PAH and SA were identified adjacent to PCA in 28%
      (32 of 114) and 14% (18 of 129) of foci examined, respectively (P = 0.007). The
      median number of proliferating nuclei increased significantly from benign
      (1.20%), SA (2.67%), PAH (3.62%), HGPIN (6.14%), to PCA (12.00%) (P < 0.001). The
      median percentage of nuclei with more than three centromeric probe signals
      (chromosome 8c gain) for SA, HGPIN, PAH, and PCA were 2.1, 2.8, 4.0, and 6.0%,
      respectively, as compared to benign prostate with 1.3% (P = 0.006). In
      conclusion, the present study identified a strong topographic association between
      PAH and PCA. PAH is also seen often to be closely associated with chronic
      inflammation. Proliferation of PAH is significantly greater than benign prostatic
      epithelium and SA but less than HGPIN or PCA. Gain of 8c is significantly greater
      in PAH than benign prostate, SA, and even HGPIN. These findings demonstrate a
      strong association between PAH and PCA, supporting its role as a neoplastic
      precursor.

PMID- 11337375
TI  - Regulation of gap junctional communication by a pro-inflammatory cytokine in
      cystic fibrosis transmembrane conductance regulator-expressing but not cystic
      fibrosis airway cells.
AB  - Airway inflammation is orchestrated by cell-cell interactions involving soluble
      mediators and cell adhesion molecules. Alterations in the coordination of the
      multicellular process of inflammation may play a major role in the chronic lung
      disease state of cystic fibrosis (CF). The aim of this study was to determine
      whether direct cell-cell interactions via gap junctional communication is
      affected during the inflammatory response of the airway epithelium. We have
      examined the strength of intercellular communication and the activation of
      nuclear factor-kappaB (NF-kappaB) in normal (non-CF) and CF human airway cell
      lines stimulated with tumor necrosis factor-alpha (TNF-alpha). TNF-alpha induced
      maximal translocation of NF-kappaB into the nucleus of non-CF as well as CF
      airway cells within 20 minutes. In non-CF cells, TNF-alpha progressively
      decreased the extent of intercellular communication. In contrast, gap junctional
      communication between CF cells exposed to TNF-alpha remained unaltered. CF
      results from mutations of the cystic fibrosis transmembrane conductance regulator
      (CFTR) gene. Interestingly, transfer of wild-type CFTR into CF cells by
      adenovirus-mediated infection was associated with the recovery of TNF-alpha
      induced uncoupling. These results suggest that expression of functional CFTR is
      necessary for regulation of gap junctional communication by TNF-alpha. Gap
      junction channels close during the inflammatory response, therefore limiting the
      intercellular diffusion of signaling molecules, and thereby the recruitment of
      neighboring cells. Defects in this mechanism may contribute to the excessive
      inflammatory response of CF airway epithelium.

PMID- 11337376
TI  - nm23-H1 suppresses invasion of oral squamous cell carcinoma-derived cell lines
      without modifying matrix metalloproteinase-2 and matrix metalloproteinase-9
      expression.
AB  - nm23-H1 is a candidate gene for the suppression of cancer metastasis. Several
      studies on human breast, hepatocellular, gastric, ovarian, and colon carcinomas
      and melanomas have shown that reduced nm23-H1 expression was closely related to
      metastatic progression with poor prognosis. However, the biochemical mechanism by
      which nm23-H1 suppresses the metastasis has yet to be elucidated. In this study,
      we analyzed the correlation between nm23 expression, cell motility, and the
      invasive abilities of six different oral squamous cell carcinoma cell lines
      (HSC2, HSC3, HSC4, KB, OSC19, and OSC20). Reduced mRNA/protein expression of the
      nm23-H1 was observed in three cell lines (HSC2, HSC3, and HSC4). These cell lines
      exhibited increased cell motility and an invasive character on organotypic raft
      culture. On the other hand, the cell lines (KB, OSC19, and OSC20) that showed a
      higher expression of nm23-H1 exhibited a threefold to fivefold reduced motility
      and also reflected fewer invasions compared to the former three cell lines.
      Because the HSC3 cells demonstrated the lowest nm23-H1 expression with the
      highest cell motility and invasive character, we established nm23-H1-transfected
      HSC3 cell lines to investigate whether exogenous nm23-H1 protein could inhibit
      cell migration and invasive activity. These transfectants showed a significant
      reduction in cell motility with exogenous nm23-H1 in a dose-dependent manner, and
      exhibited a noninvasive character. An immunofluorescence study demonstrated a
      distinct stress-fiber distribution at peripheral region of these transfectants.
      However, no significant difference of matrix metalloproteinase (MMP)-2 and MMP-9
      expression was observed between mock transfectant and nm23-H1-transfected cells.
      These findings suggest that nm23-H1 inhibits the invasive activity of oral
      squamous cell carcinoma by suppression of cell motility without altering the MMP
      2 and MMP-9 status.

PMID- 11337377
TI  - Circadian expression of clock genes in human oral mucosa and skin: association
      with specific cell-cycle phases.
AB  - We studied the relative RNA expression of clock genes throughout one 24-hour
      period in biopsies obtained from the oral mucosa and skin from eight healthy
      diurnally active male study participants. We found that the human clock genes
      hClock, hTim, hPer1, hCry1, and hBmal1 are expressed in oral mucosa and skin,
      with a circadian profile consistent with that found in the suprachiasmatic nuclei
      and the peripheral tissues of rodents. hPer1, hCry1, and hBmal1 have a rhythmic
      expression, peaking early in the morning, in late afternoon, and at night,
      respectively, whereas hClock and hTim are not rhythmic. This is the first human
      study to show a circadian profile of expression for all five clock genes as
      documented in rodents, suggesting their functional importance in man. In
      concurrent oral mucosa biopsies, thymidylate synthase enzyme activity, a marker
      for DNA synthesis, had a circadian variation with peak activity in early
      afternoon, coinciding with the timing of S phase in our previous study on cell
      cycle timing in human oral mucosa. The major peak in hPer1 expression occurs at
      the same time of day as the peak in G(1) phase in oral mucosa, suggesting a
      possible link between the circadian clock and the mammalian cell cycle.

PMID- 11337378
TI  - Comparative genomic hybridization identifies loss of 18q22-qter as an early and
      specific event in tumorigenesis of midgut carcinoids.
AB  - Carcinoid tumors are rare neuroendocrine tumors occurring in the lung or in the
      digestive tract where they are further subclassified as foregut, midgut, or
      hindgut carcinoids. To gain a better understanding of the genetic basis of the
      different types of carcinoid tumors, we have characterized numerical imbalances
      in a series of midgut carcinoids, and compared the results to previous findings
      in carcinoids from the lung. Numerical imbalances were revealed in 16 of the 18
      tumors, and the most commonly detected aberrations were losses of 18q22-qter
      (67%), 11q22-q23 (33%), and 16q21-qter (22%), and gain of 4p14-qter (22%). The
      total number of alterations found in the metastases was significantly higher than
      in the primary tumors, indicating the accumulation of acquired genetic changes in
      the tumor progression. Losses of 18q and 11q were present both in primary tumors
      and metastases, whereas loss of 16q and gain of 4 were only detected in
      metastases. Furthermore, the pattern of comparative genomic hybridization
      alterations varied depending on the total number of detected alterations. Taken
      together, the findings would suggest a progression of numerical imbalances, in
      which loss of 18q and 11q represent early events, and loss of 16q and gain of 4p
      are late events in the tumor progression of midgut carcinoids. When compared to
      previously published comparative genomic hybridization abnormalities in lung
      carcinoids, loss of 11q was found to occur in both tumor types, whereas loss of
      18q and 16q and gain of 4 were not revealed in lung carcinoids. The results
      indicate that inactivation of a putative tumor suppressor gene in 18q22-qter
      represents a frequent and early event that is specific for the development of
      midgut carcinoids.

PMID- 11337379
TI  - The beta2, alpha4, alpha5 integrins and selectins mediate chemotactic factor and
      endotoxin-enhanced neutrophil sequestration in the lung.
AB  - Intravascular chemotactic factor activation of neutrophils (polymorphonuclear
      leukocytes; PMNLs), associated with actin polymerization resulting in PMNL
      stiffening, induces rapid and transient sequestration in the pulmonary
      vasculature and lung dysfunction. Recent studies have proposed that this
      sequestration is mediated by physical lodging of PMNLs because of loss of
      deformability. To examine the contribution of cell adhesion molecules in this
      process, we used blocking monoclonal antibodies (mAbs) to rat selectins and
      integrins in a model of PMNL margination (reflected by acute blood neutropenia)
      induced by N-formyl-met-leu-phe (FMLP) chemotactic factor infusion in normal or
      lipopolysaccharide (LPS)-primed rats. Blood PMNL levels dropped by 70% within 1
      minute and for the duration of FMLP infusion (20 minutes) in normal or by 90% in
      LPS-primed rats. Pretreatment with mAbs to beta2(WT.3), VLA-4(TA-2 F(ab)(2)), and
      VLA-5 (HMalpha5 F(ab)(2)) in combination inhibited the decrease by 50% and to a
      greater degree than beta2 blockade alone (35% inhibition). F(ab)(2) mAbs to L
      (HRL-3), P-(RMP-1), plus E-(RME-1) selectins had no effect but they potentiated
      inhibition by anti-beta2 + anti-VLA-4 + anti-VLA5 mAb treatment (69% inhibition,
      P < 0.05). Similar results were observed in the first 6 minutes in LPS-primed
      rats with complete inhibition of sequestration thereafter by combined selectin
      and integrin blockade. These results indicate that besides PMNL stiffening
      because of actin polymerization, both selectins and integrins substantially
      contribute to activated PMNL sequestration in the lung.

PMID- 11337380
TI  - Heat stress contributes to the enhancement of cardiac mitochondrial complex
      activity.
AB  - Hyperthermic stress is known to protect against myocardial dysfunction after
      ischemia-reperfusion injury. It is unclear however, what energetic mechanisms are
      affected by the molecular adaptation to heat stress. We hypothesized that mild
      hyperthermic stress can increase mitochondrial respiratory enzyme activity,
      affording protection to mitochondrial energetics during prolonged cardiac
      preservation for transplantation. Rat hearts were excised after heat-stress or
      sham treatment and subjected to cold cardioplegic arrest and ischemia followed by
      reperfusion in an ex vivo perfusion system. Cardiac function, mitochondrial
      respiratory, and complex activities were assessed before and after ischemia. Heat
      shock protein (Hsp 32, 60, and 72) expression was increased in heat-stressed
      hearts. This was associated with increased mitochondrial complex activities in
      heat-stress versus sham-treated groups for complex I-V. During reperfusion,
      higher complex activities and respiratory control ratios were observed in heat
      stressed versus sham-treated groups. Recovery of ventricular function was
      improved in heat-stressed hearts. Furthermore, mitochondria in reperfused heat
      stressed myocardium exhibited intact membranes with packed, parallel, lamellar
      cristae, whereas in sham-treated myocardium, mitochondria were severely
      disrupted. This study provides the first evidence of heat-stress-mediated
      enhancement of mitochondrial energetic capacity. This is associated with
      increased tolerance to ischemia-reperfusion injury. Protection by heat stress
      against myocardial dysfunction may be partially due to enhancement of
      mitochondrial energetics.

PMID- 11337381
TI  - Increased osteoblast apoptosis in apert craniosynostosis: role of protein kinase
      C and interleukin-1.
AB  - Apert syndrome is an autosomal dominant disorder characterized by premature
      cranial ossification resulting from fibroblast growth factor receptor-2 (FGFR-2)
      activating mutations. We have studied the effects of the prominent S252W FGFR-2
      Apert mutation on apoptosis and the underlying mechanisms in human mutant
      osteoblasts. In vivo analysis of terminal deoxynucleotidyl transferase-mediated
      nick-end labeling revealed premature apoptosis of mature osteoblasts and
      osteocytes in the Apert suture compared to normal coronal suture. In vitro,
      mutant osteoblasts showed increased apoptosis, as demonstrated by terminal
      deoxynucleotidyl transferase-mediated nick-end labeling analysis, trypan blue
      staining, and DNA fragmentation. Mutant osteoblasts also showed increased
      activity of caspase-8 and effector caspases (-3, -6, -7) constitutively. This was
      related to protein kinase C activation because the selective protein kinase C
      inhibitor calphostin C inhibited caspase-8, effector caspases, and apoptosis in
      mutant osteoblasts. Apert osteoblasts also showed increased expression of
      interleukin (IL)-1alpha, IL-1beta, Fas, and Bax, and decreased Bcl-2 levels.
      Specific neutralizing anti-IL-1 antibody reduced Fas levels, Bax expression,
      effector caspases activity, and apoptosis in mutant cells. Thus, the Apert S252W
      FGFR-2 mutation promotes apoptosis in human osteoblasts through activation of
      protein kinase C, overexpression of IL-1 and Fas, activation of caspase-8, and
      increased Bax/Bcl-2 levels, leading to increased effector caspases and DNA
      fragmentation. This identifies a complex FGFR-2 signaling pathway involved in the
      premature apoptosis induced by the Apert S252W FGFR-2 mutation in human calvaria
      osteoblasts.

PMID- 11337382
TI  - Novel genomic imbalances in B-cell splenic marginal zone lymphomas revealed by
      comparative genomic hybridization and cytogenetics.
AB  - Splenic marginal zone lymphoma (SMZL) has recently been recognized in the World
      Health Organization classification of hematological diseases as distinct type of
      non-Hodgkin's lymphoma. In contrast to the well-established chromosomal changes
      associated with other B-cell non-Hodgkin's lymphoma, few genetic alterations have
      been found associated with SMZL. The aim of our study was to analyze by
      comparative genomic hybridization (CGH) the chromosomal imbalances in 29 patients
      with SMZL and to correlate these findings with clinical and biological
      characteristics and patient outcome. In 21 cases, cytogenetic studies were
      simultaneously performed. Most of the patients (83%) displayed genomic
      imbalances. A total of 111 DNA copy number changes were detected with a median of
      four abnormalities per case (range, 1 to 12). Gains (n = 92) were more frequent
      than losses (n = 16), while three high-level amplifications (3q26-q29, 5p11-p15,
      and 17q22-q25) were observed. The most frequent gains involved 3q (31%), 5q
      (28%), 12q and 20q (24% each), 9q (21%), and 4q (17%). Losses were observed in 7q
      (14%) and 17p (10%). SMZL patients with genetic losses had a shorter survival
      than the remaining SMZL patients (P < 0.05). In summary, chromosomal imbalances
      in regions 3q, 4q, 5q, 7q, 9q, 12q, and 20q have been detected by CGH in SMZL.
      Patients with SMZL displaying genetic losses by CGH had a short survival.

PMID- 11337383
TI  - Analysis of T-cell subpopulations in T-cell non-Hodgkin's lymphoma of
      angioimmunoblastic lymphadenopathy with dysproteinemia type by single target gene
      amplification of T cell receptor- beta gene rearrangements.
AB  - Angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) is defined in the
      current lymphoma classifications as a T-cell non-Hodgkin's lymphoma. However, in
      approximately one third of the cases of this lymphoproliferative disease
      rearrangements of T-cell receptor (TCR) genes indicating clonal expansion of T
      cells are not detectable. It is currently believed that these cases may represent
      early stages of a lymphoma with a minor oligoclonal T-cell population. In the
      present study, 18 lymph nodes with the characteristic histology of AILD were
      investigated for clonal T-cell receptor gene rearrangements by analysis of DNA
      extracted from whole tissue sections. Dominant T-cell clones were detected in 12
      of these cases. Single CD4(+) and CD8(+) T cells and proliferating Ki67(+) cells
      of seven cases were micromanipulated from frozen tissue sections. TCRbeta gene
      rearrangements were amplified from these cells by polymerase chain reaction and
      sequenced. In all informative cases, the clonal gene rearrangements were only
      detected among CD4(+), and not among CD8(+) T cells, indicating that the tumor
      clones in AILD usually derive from CD4(+) T cells. Minor clonal T-cell
      populations in those cases in which no clone was found by whole-tissue DNA
      analysis were not detectable even at single cell resolution. T-cell clones in 4
      of 10 cases were found to express similar TCRbeta chains, indicating a potential
      role of (super) antigen triggering in at least some cases of AILD.

PMID- 11337384
TI  - Mapping the binding domain of immunoglobulin light chains for Tamm-Horsfall
      protein.
AB  - Cast nephropathy, or myeloma kidney, is a potentially reversible cause of chronic
      renal failure. In this condition, filtered light chains bind to a common site on
      Tamm-Horsfall protein (THP), which is produced by cells of the thick ascending
      limb of the loop of HENLE: Subsequent aggregation of these proteins produces
      casts that obstruct tubule fluid flow and results in renal failure. In the
      present study, we used the yeast two-hybrid system to determine the site of
      interaction of light chains with THP. The third complementarity-determining
      region (CDR3) of both kappa and lambda light chains interacted with THP. These
      findings were confirmed in a series of competition studies using a synthetic
      peptide that corresponded to the CDR3 region and purified THP and light chains.
      Variations in the CDR3 sequence of the light chain affected binding. Thus, the
      current studies increase our understanding of the process of cast formation and
      provide an opportunity to develop strategies that may inhibit this interaction
      and prevent the clinical manifestations of myeloma kidney.

PMID- 11337385
TI  - Stepwise deletions of polyA sequences in mismatch repair-deficient colorectal
      cancers.
AB  - PolyA simple repeat sequence deletions are common in tumors with microsatellite
      instability (MSI+). Such deletions occur one base at a time in DNA mismatch
      repair (MMR)-deficient yeast suggesting larger deletions in human MSI+ tumors
      represent multiple sequential stepwise losses. Sum total deletions in four polyA
      repeats were variable (between -17 to -45 bp) in 20 sporadic MSI+ colorectal
      cancers. Progressive but less extensive total deletions (maximum of -12 bp)
      occurred in similar polyA sequences in MMR-deficient mice (mlh1-/-) up to 478
      days old. PolyA repeat lengths were relatively stable but already shortened in
      the MMR-deficient cell line HCT116. A transgene with 26 A's transfected into
      HCT116 shortened an average of 3.8 bases pairs after 469 days in culture, less
      than average deletions of BAT25 (-5.3) or BAT26 (-9.0) in MSI+ cancers. These
      findings further suggest that extensive polyA deletions common in MSI+ tumors
      likely reflect multiple stepwise smaller deletions that accumulate more than
      hundreds of divisions after loss of MMR.

PMID- 11337386
TI  - Effects of in vivo heregulin beta1 treatment in wild-type and ErbB gene-targeted
      mice depend on receptor levels and pregnancy.
AB  - Mice heterozygous (+/-) for either heregulin (HRG), ErbB2, or ErbB3 were created
      by gene targeting, resulting in the loss of one functional gene copy and an
      associated decrease in targeted protein. We examined the in vivo activity of
      recombinant HRG peptide, rHRG beta1 (amino acids 177 to 241), in the three
      heterozygous mouse lines and in wild-type (WT) mice, both pregnant and
      nonpregnant. Nonpregnant WT and HRG(+/-) mice of both sexes were sensitive to
      rHRG beta1 treatment as evidenced by a high mortality rate associated with
      abdominal enlargement and parietal cell loss. However, pregnant WT mice and ErbB2
      and ErbB3 heterozygous mice treated with rHRG beta1 were less affected, with
      significantly lower mortality rates and a less severe abdominal phenotype.
      Histological analysis revealed extensive breast ductal hyperplasia in females of
      all genotypes after rHRG beta1 treatment. Hyperplasia of other epithelial tissues
      such as the pancreas and intestine and the growth of cardiac nerve bundles were
      also observed, independent of sex.

PMID- 11337388
TI  - Bcl-2 expression in anaplastic large cell lymphoma.

PMID- 11337389
TI  - Formation of granulomas in the lungs of severe combined immunodeficient mice
      after infection with bacillus Calmette-Guerin.

PMID- 11337387
TI  - Immunopathology and ehrlichial propagation are regulated by interferon-gamma and
      interleukin-10 in a murine model of human granulocytic ehrlichiosis.
AB  - Previous studies of human granulocytic ehrlichiosis (HGE) suggest a role for host
      immune response in resolving infection and in causing histopathological lesions.
      We hypothesize that interferon (IFN)-gamma allows tissue injury that is
      suppressed by interleukin (IL)-10 after initiation by ehrlichia infection. Thus,
      parental C57BL/6, IL-10-/-, and IFN-gamma-/- strains of mice were infected and
      then assayed for hepatic histopathological lesions, ehrlichial burden, and
      cytokine responses to ehrlichial antigen in primary splenic cultures during the
      first 21 days after infection. Histopathological severity in C57/BL6 and IL-10-/-
      mice rose in parallel through day 7, but then diverged as pathology in IL-10-/-
      mice continued to increase and remained high throughout the course of the study.
      The histopathological rank of C57BL/6 of mice decreased at day 10 and returned to
      baseline levels at days 14 and 21. In contrast, the IFN-gamma-/- strain had
      baseline pathology scores throughout the course of the infection, yet had
      significantly higher ehrlichial burden both in the blood and tissues than C57BL/6
      or IL-10-/- mice. This suggests that histopathological lesions in the HGE murine
      model do not result from direct ehrlichia-mediated injury but from
      immunopathological mechanisms initiated by ehrlichial infection. The similarities
      with lesions in humans suggest an immunopathological basis for HGE.

PMID- 11337390
TI  - FIFTY YEARS AS A PLANT PHYSIOLOGIST.
AB  - This chapter is a chronological and biographical sketch of the professional life
      of a botanist-plant physiologist. He just happens to be of African-American
      descent. He cites his early education and through college and graduate school, as
      well as his war years at the University of Chicago. His postdoc appointment at
      Caltech with James Bonner was really his professional beginning and highlight.
      Most of his teaching and research years were spent at Tuskegee University and the
      George Washington Carver Research Foundation. He spent several tours of research
      activity, in both the United States and foreign countries. His contact with plant
      physiologists was quite broad, both in the United States and overseas. Finally,
      in his senior years, he has turned to mentoring young students into careers in
      the biological and allied sciences. This activity, he states, has "kept me young
      beyond my chronological age."

PMID- 11337391
TI  - ALKALOID BIOSYNTHESIS IN PLANTS: Biochemistry, Cell Biology, Molecular
      Regulation, and Metabolic Engineering Applications.
AB  - Recent advances in the cell, developmental, and molecular biology of alkaloid
      biosynthesis have heightened our appreciation for the complexity and importance
      of plant secondary pathways. Several biosynthetic genes involved in the formation
      of tropane, benzylisoquinoline, and terpenoid indole alkaloids have now been
      isolated. The early events of signal perception, the pathways of signal
      transduction, and the function of gene promoters have been studied in relation to
      the regulation of alkaloid metabolism. Enzymes involved in alkaloid biosynthesis
      are associated with diverse subcellular compartments including the cytosol,
      vacuole, tonoplast membrane, endoplasmic reticulum, chloroplast stroma, thylakoid
      membranes, and perhaps unique "biosynthetic" or transport vesicles. Localization
      studies have shown that sequential alkaloid biosynthetic enzymes can also occur
      in distinct cell types, suggesting the intercellular transport of pathway
      intermediates. Isolated genes have also been used to genetically alter the
      accumulation of specific alkaloids and other plant secondary metabolites.
      Metabolic modifications include increased indole alkaloid levels, altered tropane
      alkaloid accumulation, elevated serotonin synthesis, reduced indole glucosinolate
      production, redirected shikimate metabolism, and increased cell wall-bound
      tyramine formation. This review discusses the biochemistry, cell biology,
      molecular regulation, and metabolic engineering of alkaloid biosynthesis in
      plants.

PMID- 11337392
TI  - HOW GIBBERELLIN REGULATES PLANT GROWTH AND DEVELOPMENT: A Molecular Genetic
      Analysis of Gibberellin Signaling.
AB  - Gibberellins are hormones that control growth and a wide variety of other plant
      developmental processes. In recent years, significant progress has been made on
      the biochemistry of gibberellin biosynthesis and on the mechanisms by which
      gibberellin levels are regulated in plants. There have also been major advances
      in the understanding of gibberellin signaling, with several key genes being
      cloned. This review discusses our current understanding of gibberellin signaling,
      as seen from the perspective of molecular genetic analysis, and relates these
      observations to previous biochemical studies. In particular, we highlight an
      important conclusion of recent years: that GAI/RGA and orthologs play major roles
      in gibberellin signaling in diverse plant species, and that gibberellin probably
      stimulates growth by derepression of GAI/RGA.

PMID- 11337393
TI  - CYTOKININ METABOLISM AND ACTION.
AB  - Cytokinins are structurally diverse and biologically versatile. The chemistry and
      physiology of cytokinin have been studied extensively, but the regulation of
      cytokinin biosynthesis, metabolism, and signal transduction is still largely
      undefined. Recent advances in cloning metabolic genes and identifying putative
      receptors portend more rapid progress based on molecular techniques. This review
      centers on cytokinin metabolism with connecting discussions on biosynthesis and
      signal transduction. Important findings are summarized with emphasis on metabolic
      enzymes and genes. Based on the information generated to date, implications and
      future research directions are presented.

PMID- 11337394
TI  - ONE-CARBON METABOLISM IN HIGHER PLANTS.
AB  - The metabolism of one-carbon (C1) units is essential to plants, and plant C1
      metabolism has novel features not found in other organisms-plus some enigmas.
      Despite its centrality, uniqueness, and mystery, plant C1 biochemistry has
      historically been quite poorly explored, in part because its enzymes and
      intermediates tend to be labile and low in abundance. Fortunately, the
      integration of molecular and genetic approaches with biochemical ones is now
      driving rapid advances in knowledge of plant C1 enzymes and genes. An overview of
      these advances is presented. There has also been progress in measuring C1
      metabolite fluxes and pool sizes, although this remains challenging and there are
      relatively few data. In the future, combining reverse genetics with flux and pool
      size determinations should lead to quantitative understanding of how plant C1
      pathways function. This is a prerequisite for their rational engineering.

PMID- 11337395
TI  - CIRCADIAN RHYTHMS IN PLANTS.
AB  - Circadian rhythms, endogenous rhythms with periods of approximately 24 h, are
      widespread in nature. Although plants have provided many examples of rhythmic
      outputs and our understanding of photoreceptors of circadian input pathways is
      well advanced, studies with plants have lagged in the identification of
      components of the central circadian oscillator. Nonetheless, genetic and
      molecular biological studies, primarily in Arabidopsis, have begun to identify
      the components of plant circadian systems at an accelerating pace. There also is
      accumulating evidence that plants and other organisms house multiple circadian
      clocks both in different tissues and, quite probably, within individual cells,
      providing unanticipated complexity in circadian systems.

PMID- 11337396
TI  - MACRONUTRIENT UTILIZATION BY PHOTOSYNTHETIC EUKARYOTES AND THE FABRIC OF
      INTERACTIONS.
AB  - Organisms acclimate to a continually fluctuating nutrient environment.
      Acclimation involves responses specific for the limiting nutrient as well as
      responses that are more general and occur when an organism experiences different
      stress conditions. Specific responses enable organisms to efficiently scavenge
      the limiting nutrient and may involve the induction of high-affinity transport
      systems and the synthesis of hydrolytic enzymes that facilitate the release of
      the nutrient from extracellular organic molecules or from internal reserves.
      General responses include changes in cell division rates and global alterations
      in metabolic activities. In photosynthetic organisms there must be precise
      regulation of photosynthetic activity since when severe nutrient limitation
      prevents continued cell growth, excitation of photosynthetic pigments could
      result in the formation of reactive oxygen species, which can severely damage
      structural and functional features of the cell. This review focuses on ways that
      photosynthetic eukaryotes assimilate the macronutrients nitrogen, sulfur, and
      phosphorus, and the mechanisms that govern assimilatory activities. Also
      discussed are molecular responses to macronutrient limitation and the elicitation
      of those responses through integration of environmental and cellular cues.

PMID- 11337397
TI  - PLANT PHOSPHOLIPASES.
AB  - Phospholipases are a diverse series of enzymes that hydrolyze phospholipids.
      Multiple forms of phospholipases D, C, and A have been characterized in plants.
      These enzymes are involved in a broad range of functions in cellular regulation,
      lipid metabolism, and membrane remodeling. In recent years, increasing attention
      has been paid to the many roles of phospholipases in signal transduction. This
      review highlights recent developments in the understanding of biochemical,
      molecular biological, and functional aspects of various phospholipases in plants.

PMID- 11337398
TI  - ENDOSPERM DEVELOPMENT: Cellularization and Cell Fate Specification.
AB  - The endosperm develops from the central cell of the megagametophyte after
      introduction of the second male gamete into the diploid central cell. Of the
      three forms of endosperm in angiosperms, the nuclear type is prevalent in
      economically important species, including the cereals. Landmarks in nuclear
      endosperm development are the coenocytic, cellularization, differentiation, and
      maturation stages. The differentiated endosperm contains four major cell types:
      starchy endosperm, aleurone, transfer cells, and the cells of the embryo
      surrounding region. Recent research has demonstrated that the first two phases of
      endosperm occur via mechanisms that are conserved among all groups of
      angiosperms, involving directed nuclear migration during the coenocytic stage and
      anticlinal cell wall deposition by cytoplasmic phragmoplasts formed in interzones
      between radial microtubular systems emanating from nuclear membranes. Complete
      cellularization of the endosperm coenocyte is achieved through centripetal growth
      of cell files, extending to the center of the endosperm cavity. Key points in
      cell cycle control and control of the MT (microtubular) cytoskeletal apparatus
      central to endosperm development are discussed. Specification of cell fates in
      the cereal endosperm appears to occur via positional signaling; cells in
      peripheral positions, except over the main vascular tissues, assume aleurone cell
      fate. Cells over the main vascular tissue become transfer cells and all interior
      cells become starchy endosperm cells. Studies in maize have implicated Crinkly4,
      a protein receptor kinase-like molecule, in aleurone cell fate specification.

PMID- 11337399
TI  - MECHANISTIC FEATURES OF THE MO-CONTAINING NITROGENASE.
AB  - Nitrogenase is the complex metalloenzyme responsible for biological dinitrogen
      reduction. This reaction represents the single largest contributor to the
      reductive portion of the global nitrogen cycle. Recent developments in
      understanding the mechanism of the Mo-based nitrogenase are reviewed. Topics
      include how nucleotide binding and hydrolysis are coupled to electron transfer
      and substrate reduction, how electrons are accumulated and transferred within the
      MoFe-protein, and how substrates bind and are reduced at the active site metal
      cluster.

PMID- 11337400
TI  - MOLECULAR ENGINEERING OF C4 PHOTOSYNTHESIS.
AB  - The majority of terrestrial plants, including many important crops such as rice,
      wheat, soybean, and potato, are classified as C3 plants that assimilate
      atmospheric CO2 directly through the C3 photosynthetic pathway. C4 plants such as
      maize and sugarcane evolved from C3 plants, acquiring the C4 photosynthetic
      pathway to achieve high photosynthetic performance and high water- and nitrogen
      use efficiencies. The recent application of recombinant DNA technology has made
      considerable progress in the molecular engineering of C4 photosynthesis over the
      past several years. It has deepened our understanding of the mechanism of C4
      photosynthesis and provided valuable information as to the evolution of the C4
      photosynthetic genes. It also has enabled us to express enzymes involved in the
      C4 pathway at high levels and in desired locations in the leaves of C3 plants for
      engineering of primary carbon metabolism.

PMID- 11337401
TI  - THE PLASTID DIVISION MACHINE.
AB  - Plastid division is essential for the maintenance of plastid populations in cells
      undergoing division and for the accumulation of large chloroplast numbers in
      photosynthetic tissues. Although the mechanisms mediating plastid division are
      poorly understood, ultrastructural studies imply this process is accomplished by
      a dynamic macromolecular machine organized into ring structures at the plastid
      midpoint. A key component of the engine that powers this machine is the motor
      like protein FtsZ, a cytoskeletal GTPase of endosymbiotic origin that forms a
      ring at the plastid division site, similar to the function of its prokaryotic
      relatives in bacterial cytokinesis. This review considers the phylogenetic
      distribution and structural properties of two recently identified plant FtsZ
      protein families in the context of their distinct roles in plastid division and
      describes current evidence regarding factors that govern their placement at the
      division site. Because of their evolutionary and mechanistic relationship, the
      process of bacterial cell division provides a valuable, though incomplete,
      paradigm for understanding plastid division in plants.

PMID- 11337402
TI  - VARIATIONS IN THE BIOSYNTHESIS OF SEED-STORAGE LIPIDS.
AB  - In many plants lipids represent up to 80% of dry weight of storage tissues. In
      seeds, lipids accumulate as triacylglycerols (TAGs), which are formed by an
      extension of the membrane-lipid biosynthetic pathway common to all plant tissues.
      In contrast to the conserved fatty acid (FA) composition of membrane lipids, the
      observed divergence in seed oil acyl chains among different species is very high.
      The acyl groups of seed TAGs can vary in their chain length (from 8 to 24) as
      well as in their degree of unsaturation. In addition to methylene-interrupted
      double bonds, many seeds contain TAGs that have unusual functional groups in
      their FAs, such as hydroxyl, oxirane, or acetylene groups. All of the major steps
      in the biosynthetic pathway to TAG are now known and sequence information for
      genes encoding most of the enzymes involved is available. Here we present the
      current knowledge of the metabolic mechanisms involved in the divergence from the
      membrane-lipid biosynthetic pathway during storage lipid formation.

PMID- 11337403
TI  - CHLAMYDOMONAS AS A MODEL ORGANISM.
AB  - The unicellular green alga Chlamydomonas offers a simple life cycle, easy
      isolation of mutants, and a growing array of tools and techniques for molecular
      genetic studies. Among the principal areas of current investigation using this
      model system are flagellar structure and function, genetics of basal bodies
      (centrioles), chloroplast biogenesis, photosynthesis, light perception, cell-cell
      recognition, and cell cycle control. A genome project has begun with compilation
      of expressed sequence tag data and gene expression studies and will lead to a
      complete genome sequence. Resources available to the research community include
      wild-type and mutant strains, plasmid constructs for transformation studies, and
      a comprehensive on-line database.

PMID- 11337404
TI  - ISOPRENE EMISSION FROM PLANTS.
AB  - Very large amounts of isoprene are emitted from vegetation, especially from
      mosses, ferns, and trees. This hydrocarbon flux to the atmosphere, roughly equal
      to the flux of methane, has a large effect on the oxidizing potential of the
      atmosphere. Isoprene emission results from de novo synthesis by the deoxyxylulose
      phosphate/methyl erythritol 4-phosphate pathway in plastids. Dimethylallyl
      pyrophosphate made by this pathway is converted to isoprene by isoprene synthase.
      Isoprene synthase activity in plants has a high pH optimum and requirement for
      Mg2+ that is consistent with its location inside chloroplasts. Isoprene emission
      costs the plant significant amounts of carbon, ATP, and reducing power.
      Researchers hypothesize that plants benefit from isoprene emission because it
      helps photosynthesis recover from short high-temperature episodes. The evolution
      of isoprene emission may have been important in allowing plants to survive the
      rapid temperature changes that can occur in air because of the very low heat
      capacity of isoprene relative to water.

PMID- 11337405
TI  - BIOSYNTHESIS OF ASCORBIC ACID IN PLANTS: A Renaissance.
AB  - The structure of the familiar antioxidant L-ascorbic acid (vitamin C) was
      described in 1933 yet remarkably, its biosynthesis in plants remained elusive
      until only recently. It became clear from radioisotopic labeling studies in the
      1950s that plant ascorbic acid biosynthesis does not proceed in toto via a route
      similar to that in mammals. The description in 1996 of an Arabidopsis thaliana
      mutant deficient in ascorbic acid prompted renewed research effort in this area,
      and subsequently in 1998 a new pathway was discovered that is backed by strong
      biochemical and molecular genetic evidence. This pathway proceeds through the
      intermediates GDP-D-mannose, L-galactose, and L-galactono-1,4-lactone. Much
      research has focused on the properties of the terminal enzyme responsible for
      conversion of the aldonolactone to ascorbate, and on related enzymes in both
      mammals and fungi. Two of the plant biosynthetic genes have been studied at the
      molecular level and additional ascorbate-deficient A. thaliana mutants may hold
      the key to other proteins involved in plant ascorbate metabolism. An analysis of
      the biosynthesis of ascorbate and its analogues in algae and fungi as well as the
      study of alternative proposed pathways should broaden our understanding of
      ascorbate metabolism in plants. With a biosynthetic pathway in hand, research on
      areas such as the control of ascorbate biosynthesis and the physiological roles
      of ascorbate should progress rapidly.

PMID- 11337406
TI  - TONOPLAST TRANSPORTERS: Organization and Function.
AB  - Regulation of the contents and volume of vacuoles in plant cells depends on the
      coordinated activities of transporters and channels located in the tonoplast
      (vacuolar membrane). The three major components of the tonoplast are two proton
      pumps, the vacuolar H+-ATPase (V-ATPase) and H+-pyrophosphatase (V-PPase), and
      aquaporins. The tertiary structure of the V-ATPase complex and properties of its
      subunits have been characterized by biochemical and genetic techniques. These
      studies and a comparison with the F-type ATPase have enabled estimation of the
      dynamics of V-ATPase activity during catalysis. V-PPase, a simple proton pump,
      has been identified and cloned from various plant species and other organisms,
      such as algae and phototrophic bacteria, and functional motifs of the enzyme have
      been determined. Aquaporin, serving as the water channel, is the most abundant
      protein in the tonoplast in most plants. A common molecular architecture of
      aquaporins in mammals and plants has been determined by two-dimensional
      crystallographic analysis. Furthermore, recent molecular biological studies have
      revealed several other types of tonoplast transporters, such as the Ca2+-ATPase,
      Ca2+/H+ antiporter and Na+/H+ antiporter. Many other transporters and channels in
      the tonoplast remain to be identified; their activities have already been
      detected. This review presents an overview of the field and discusses recent
      findings on the tonoplast protein components that have been identified and their
      physiological consequences.

PMID- 11337407
TI  - PROBING PLANT METABOLISM WITH NMR.
AB  - Analytical methods for probing plant metabolism are taking on new significance in
      the era of functional genomics and metabolic engineering. Among the available
      methods, nuclear magnetic resonance (NMR) spectroscopy is a technique that can
      provide insights into the integration and regulation of plant metabolism through
      a combination of in vivo and in vitro measurements. Thus NMR can be used to
      identify, quantify, and localize metabolites, to define the intracellular
      environment, and to explore pathways and their operation. We review these
      applications and their significance from a metabolic perspective. Topics of
      current interest include applications of NMR to metabolic flux analysis,
      metabolite profiling, and metabolite imaging. These and other areas are discussed
      in relation to NMR investigations of intermediary carbon and nitrogen metabolism.
      We conclude that metabolic NMR has a continuing role to play in the development
      of a quantitative understanding of plant metabolism and in the characterization
      of metabolic phenotypes.

PMID- 11337408
TI  - FUNCTION AND MECHANISM OF ORGANIC ANION EXUDATION FROM PLANT ROOTS.
AB  - The rhizosphere is the zone of soil immediately surrounding plant roots that is
      modified by root activity. In this critical zone, plants perceive and respond to
      their environment. As a consequence of normal growth and development, a large
      range of organic and inorganic substances are exchanged between the root and
      soil, which inevitably leads to changes in the biochemical and physical
      properties of the rhizosphere. Plants also modify their rhizosphere in response
      to certain environmental signals and stresses. Organic anions are commonly
      detected in this region, and their exudation from plant roots has now been
      associated with nutrient deficiencies and inorganic ion stresses. This review
      summarizes recent developments in the understanding of the function, mechanism,
      and regulation of organic anion exudation from roots. The benefits that plants
      derive from the presence of organic anions in the rhizosphere are described and
      the potential for biotechnology to increase organic anion exudation is
      highlighted.

PMID- 11337409
TI  - PLANT MITOCHONDRIA AND OXIDATIVE STRESS: Electron Transport, NADPH Turnover, and
      Metabolism of Reactive Oxygen Species.
AB  - The production of reactive oxygen species (ROS), such as O2- and H2O2, is an
      unavoidable consequence of aerobic metabolism. In plant cells the mitochondrial
      electron transport chain (ETC) is a major site of ROS production. In addition to
      complexes I-IV, the plant mitochondrial ETC contains a non-proton-pumping
      alternative oxidase as well as two rotenone-insensitive, non-proton-pumping
      NAD(P)H dehydrogenases on each side of the inner membrane: NDex on the outer
      surface and NDin on the inner surface. Because of their dependence on Ca2+, the
      two NDex may be active only when the plant cell is stressed. Complex I is the
      main enzyme oxidizing NADH under normal conditions and is also a major site of
      ROS production, together with complex III. The alternative oxidase and possibly
      NDin(NADH) function to limit mitochondrial ROS production by keeping the ETC
      relatively oxidized. Several enzymes are found in the matrix that, together with
      small antioxidants such as glutathione, help remove ROS. The antioxidants are
      kept in a reduced state by matrix NADPH produced by NADP-isocitrate dehydrogenase
      and non-proton-pumping transhydrogenase activities. When these defenses are
      overwhelmed, as occurs during both biotic and abiotic stress, the mitochondria
      are damaged by oxidative stress.

PMID- 11337410
TI  - PHOTOSYSTEM I: Function and Physiology.
AB  - Photosystem I is the light-driven plastocyanin-ferredoxin oxidoreductase in the
      thylakoid membranes of cyanobacteria and chloroplasts. In recent years,
      sophisticated spectroscopy, molecular genetics, and biochemistry have been used
      to understand the light conversion and electron transport functions of
      photosystem I. The light-harvesting complexes and internal antenna of photosystem
      I absorb photons and transfer the excitation energy to P700, the primary electron
      donor. The subsequent charge separation and electron transport leads to the
      reduction of ferredoxin. The photosystem I proteins are responsible for the
      precise arrangement of cofactors and determine redox properties of the electron
      transfer centers. With the availability of genomic information and the structure
      of photosystem I, one can now probe the functions of photosystem I proteins and
      cofactors. The strong reductant produced by photosystem I has a central role in
      chloroplast metabolism, and thus photosystem I has a critical role in the
      metabolic networks and physiological responses in plants.

PMID- 11337411
TI  - GUARD CELL SIGNAL TRANSDUCTION.
AB  - Guard cells surround stomatal pores in the epidermis of plant leaves and stems.
      Stomatal pore opening is essential for CO2 influx into leaves for photosynthetic
      carbon fixation. In exchange, plants lose over 95% of their water via
      transpiration to the atmosphere. Signal transduction mechanisms in guard cells
      integrate hormonal stimuli, light signals, water status, CO2, temperature, and
      other environmental conditions to modulate stomatal apertures for regulation of
      gas exchange and plant survival under diverse conditions. Stomatal guard cells
      have become a highly developed model system for characterizing early signal
      transduction mechanisms in plants and for elucidating how individual signaling
      mechanisms can interact within a network in a single cell. In this review we
      focus on recent advances in understanding signal transduction mechanisms in guard
      cells.

PMID- 11337412
TI  - TRANSPORTERS RESPONSIBLE FOR THE UPTAKE AND PARTITIONING OF NITROGENOUS SOLUTES.
AB  - The acquisition and allocation of nitrogenous compounds are essential processes
      in plant growth and development. The huge economic and environmental costs
      resulting from the application of nitrogen fertilizers make this topic very
      important. A diverse array of transporters varying in their expression pattern
      and also in their affinity, specificity, and capacity for nitrogenous compounds
      has been identified. Now the future challenge is to define their individual
      contribution to nitrogen nutrition and signalling processes. Here we have
      reviewed recent advances in the identification and molecular characterization of
      these transporters, concentrating on mechanisms existing at the plasma membrane.
      The review focuses on nitrate, ammonium, and amino acid transporter familes, but
      we also briefly describe what is known at the molecular level about peptide
      transporters and a recently identified family implicated in the transport of
      purines and their derivatives.

PMID- 11337413
TI  - DEFENSIVE RESIN BIOSYNTHESIS IN CONIFERS.
AB  - Tree killing bark beetles and their vectored fungal pathogens are the most
      destructive agents of conifer forests worldwide. Conifers defend against attack
      by the constitutive and inducible production of oleoresin, a complex mixture of
      mono-, sesqui-, and diterpenoids that accumulates at the wound site to kill
      invaders and both flush and seal the injury. Although toxic to the bark beetle
      and fungal pathogen, oleoresin also plays a central role in the chemical ecology
      of these boring insects, from host selection to pheromone signaling and
      tritrophic level interactions. The biochemistry of oleoresin terpenoids is
      reviewed, and the regulation of production of this unusual plant secretion is
      described in the context of bark beetle infestation dynamics with respect to the
      function of the turpentine and rosin components. Recent advances in the molecular
      genetics of terpenoid biosynthesis provide evidence for the evolutionary origins
      of oleoresin and permit consideration of genetic engineering strategies to
      improve conifer defenses as a component of modern forest biotechnology.

PMID- 11337414
TI  - MOLECULAR BIOLOGY OF FRUIT MATURATION AND RIPENING.
AB  - The development and maturation of fruits has received considerable scientific
      scrutiny because of both the uniqueness of such processes to the biology of
      plants and the importance of fruit as a significant component of the human diet.
      Molecular and genetic analysis of fruit development, and especially ripening of
      fleshy fruits, has resulted in significant gains in knowledge over recent years.
      Great strides have been made in the areas of ethylene biosynthesis and response,
      cell wall metabolism, and environmental factors, such as light, that impact
      ripening. Discoveries made in Arabidopsis in terms of general mechanisms for
      signal transduction, in addition to specific mechanisms of carpel development,
      have assisted discovery in more traditional models such as tomato. This review
      attempts to coalesce recent findings in the areas of fruit development and
      ripening.

PMID- 11337415
TI  - CYTOKINESIS AND BUILDING OF THE CELL PLATE IN PLANTS.
AB  - Cytokinesis in plant cells is more complex than in animals, as it involves
      building a cell plate as the final step in generating two cells. The cell plate
      is built in the center of phragmoplast by fusion of Golgi-derived vesicles. This
      step imposes an architectural problem where ballooning of the fused structures
      has to be avoided to create a plate instead. This is apparently achieved by
      squeezing the vesicles into dumbbell-shaped vesicle-tubule-vesicle (VTV)
      structures with the help of phragmoplastin, a homolog of dynamin. These
      structures are fused at their ends in a star-shaped body creating a
      tubulovesicular "honeycomb-like" structure sandwiched between the positive ends
      of the phragmoplast microtubules. This review summarizes our current
      understanding of various mechanisms involved in budding-off of Golgi vesicles,
      delivery and fusion of vesicles to initiate cell plate, and the synthesis of
      polysaccharides at the forming cell plate. Little is known about the molecular
      mechanisms involved in determining the site, direction, and the point of
      attachment of the growing cell plate with the parental cell wall. These gaps may
      be filled soon, as many genes that have been identified by mutations are analyzed
      and functions of their products are deciphered.

PMID- 11337416
TI  - RIBOSOME-INACTIVATING PROTEINS: A Plant Perspective.
AB  - Ribosome-inactivating proteins (RIPs) are toxic N-glycosidases that depurinate
      the universally conserved alpha-sarcin loop of large rRNAs. This depurination
      inactivates the ribosome, thereby blocking its further participation in protein
      synthesis. RIPs are widely distributed among different plant genera and within a
      variety of different tissues. Recent work has shown that enzymatic activity of at
      least some RIPs is not limited to site-specific action on the large rRNAs of
      ribosomes but extends to depurination and even nucleic acid scission of other
      targets. Characterization of the physiological effects of RIPs on mammalian cells
      has implicated apoptotic pathways. For plants, RIPs have been linked to defense
      by antiviral, antifungal, and insecticidal properties demonstrated in vitro and
      in transgenic plants. How these effects are brought about, however, remains
      unresolved. At the least, these results, together with others summarized here,
      point to a complex biological role. With genetic, genomic, molecular, and
      structural tools now available for integrating different experimental approaches,
      we should further our understanding of these multifunctional proteins and their
      physiological functions in plants.

PMID- 11337417
TI  - PLANT PLASMA MEMBRANE H+-ATPases: Powerhouses for Nutrient Uptake.
AB  - Most transport proteins in plant cells are energized by electrochemical gradients
      of protons across the plasma membrane. The formation of these gradients is due to
      the action of plasma membrane H+ pumps fuelled by ATP. The plasma membrane H+
      ATPases share a membrane topography and general mechanism of action with other P
      type ATPases, but differ in regulatory properties. Recent advances in the field
      include the identification of the complete H+-ATPase gene family in Arabidopsis,
      analysis of H+-ATPase function by the methods of reverse genetics, an improved
      understanding of the posttranslational regulation of pump activity by 14-3-3
      proteins, novel insights into the H+ transport mechanism, and progress in
      structural biology. Furthermore, the elucidation of the three-dimensional
      structure of a related Ca2+ pump has implications for understanding of structure
      function relationships for the plant plasma membrane H+-ATPase.

PMID- 11337418
TI  - THE COHESION-TENSION MECHANISM AND THE ACQUISITION OF WATER BY PLANT ROOTS.
AB  - The physical basis and evidence in support of the cohesion-tension theory of the
      ascent of sap in plants are reviewed. The focus is on the recent discussion of
      challenges to the cohesion-tension mechanism based on measurements with the
      pressure probe. Limitations of pressure probes to measure tensions (negative
      pressures) in intact transpiring plants are critically assessed. The possible
      role of the cohesion-tension mechanism during the acquisition of water and
      solutes by plant roots is discussed.

PMID- 11337419
TI  - Why are doctors so unhappy? There are probably many causes, some of them deep.

PMID- 11337420
TI  - Is transmitted drug resistance in HIV on the rise? It seems so.

PMID- 11337421
TI  - Dysfunctional breathing and asthma. It is important to tell the difference.

PMID- 11337422
TI  - Newly available treatments for nicotine addiction. Smokers wanting help with
      stopping now have effective treatment options.

PMID- 11337423
TI  - Why Britain needs a nicotine regulation authority. To bring consistency and
      regulation to tobacco and alternative nicotine products.

PMID- 11337424
TI  - Milburn's vision of a new NHS. Adopting the missionary position.

PMID- 11337425
TI  - Understanding the burden of musculoskeletal conditions. The burden is huge and
      not reflected in national health priorities.

PMID- 11337426
TI  - NHS faces medical negligence bill of pound 2.6bn.

PMID- 11337427
TI  - Doctors say they are not influenced by drug companies' promotions.

PMID- 11337429
TI  - GPs shut surgeries in protest at government targets.

PMID- 11337430
TI  - UN calls for $10 bn to wage war on AIDS.

PMID- 11337431
TI  - Milburn proposes to decentralise the NHS.

PMID- 11337432
TI  - US report finds no link between MMR and autism.

PMID- 11337433
TI  - UK investigates possible human cases of foot and mouth disease.

PMID- 11337434
TI  - Diplomatic champion of wide public health issues.

PMID- 11337435
TI  - Analysis of prevalence of HIV-1 drug resistance in primary infections in the
      United Kingdom.
AB  - OBJECTIVES: To identify changes since 1994 in the prevalence of resistance to
      anti-HIV drugs in primary HIV-1 infections in the United Kingdom. DESIGN:
      Retrospective and prospective assessment of viruses obtained from people recently
      infected with HIV. SETTING: Multiple centres (patients enrolled in the UK
      register of seroconverters) and a single large HIV clinic (active case
      ascertainment). PARTICIPANTS: 69 patients infected with HIV between June 1994 and
      August 2000. MAIN OUTCOME MEASURES: Prevalence of key mutations associated with
      drug resistance in the reverse transcriptase and protease genes of HIV-1, by year
      of infection. RESULTS: Between June 1994 and August 2000, 10 (14%) of 69 newly
      infected patients had one or more key HIV-1 mutations associated with drug
      resistance. The risk of being infected with drug resistant virus increased over
      time (adjusted relative risk per year 1.74 (95% confidence interval 0.93 to
      3.27), P=0.06). The estimated prevalence of drug resistance in those infected in
      2000 was 27% (12% to 48%). CONCLUSIONS: Transmission of drug resistant HIV-1 in
      the United Kingdom seems to be increasing. New approaches to encourage safer
      sexual behaviour in all sectors of the population are urgently needed.

PMID- 11337436
TI  - Incidence and predictors of severe obstetric morbidity: case-control study.
AB  - OBJECTIVE: To estimate the incidence and predictors of severe obstetric
      morbidity. DESIGN: Development of definitions of severe obstetric morbidity by
      literature review. Case-control study from a defined delivery population with
      four randomly selected pregnant women as controls for every case. SETTING: All 19
      maternity units within the South East Thames region and six neighbouring
      hospitals caring for pregnant women from the region between 1 March 1997 and 28
      February 1998. PARTICIPANTS: 48 865 women who delivered during the time frame.
      RESULTS: There were 588 cases of severe obstetric morbidity giving an incidence
      of 12.0/1000 deliveries (95% confidence interval 11.2 to 13.2). During the study
      there were five maternal deaths attributed to conditions studied. Disease
      specific morbidities per 1000 deliveries were 6.7 (6.0 to 7.5) for severe
      haemorrhage, 3.9 (3.3 to 4.5) for severe pre-eclampsia, 0.2 (0.1 to 0.4) for
      eclampsia, 0.5 (0.3 to 0.8) for HELLP (Haemolysis, Elevated Liver enzymes, and
      Low Platelets) syndrome, 0.4 (0.2 to 0.6) for severe sepsis, and 0.2 (0.1 to 0.4)
      for uterine rupture. Age over 34 years, non-white ethnic group, past or current
      hypertension, previous postpartum haemorrhage, delivery by emergency caesarean
      section, antenatal admission to hospital, multiple pregnancy, social exclusion,
      and taking iron or anti-depressants at antenatal booking were all independently
      associated with morbidity after adjustment. CONCLUSION: Severe obstetric
      morbidity and its relation to mortality may be more sensitive measures of
      pregnancy outcome than mortality alone. Most events are related to obstetric
      haemorrhage and severe pre-eclampsia. Caesarean section quadruples the risk of
      morbidity. Development and evaluation of ways of predicting and reducing risk are
      required with particular emphasis paid on the management of haemorrhage and pre
      eclampsia.

PMID- 11337437
TI  - Increasing prevalence of obesity in primary school children: cohort study.

PMID- 11337438
TI  - Age of menarche in contemporary British teenagers: survey of girls born between
      1982 and 1986.

PMID- 11337439
TI  - Validity study of the severity index, a simple measure of urinary incontinence in
      women.

PMID- 11337441
TI  - Prevalence of dysfunctional breathing in patients treated for asthma in primary
      care: cross sectional survey.
AB  - OBJECTIVES: To estimate the prevalence of dysfunctional breathing in adults with
      asthma treated in the community. DESIGN: Postal questionnaire survey using
      Nijmegen questionnaire. SETTING: One general practice with 7033 patients.
      PARTICIPANTS: All adult patients aged 17-65 with diagnosed asthma who were
      receiving treatment. MAIN OUTCOME MEASURE: Score >/=23 on Nijmegen questionnaire.
      RESULTS: 227/307 patients returned completed questionnaires; 219 (71.3%)
      questionnaires were suitable for analysis. 63 participants scored >/=23. Those
      scoring >/=23 were more likely to be female than male (46/132 (35%) v 17/87
      (20%), P=0.016) and were younger (mean (SD) age 44.8 (14.7) v 49.0 (13.8,
      (P=0.05). Patients at different treatment steps of the British Thoracic Society
      asthma guidelines were affected equally. CONCLUSIONS: About a third of women and
      a fifth of men had scores suggestive of dysfunctional breathing. Although further
      studies are needed to confirm the validity of this screening tool and these
      findings, these prevalences suggest scope for therapeutic intervention and may
      explain the anecdotal success of the Buteyko method of treating asthma.

PMID- 11337442
TI  - Use of computer terminals on wards to access emergency test results: a
      retrospective audit.
AB  - OBJECTIVE: To assess delay in clinicians obtaining emergency biochemistry test
      results when the telephoning of results by laboratory staff is supplanted by
      installation of computer ward terminals. DESIGN: Retrospective observational
      study. SETTING: Accident and emergency department and acute medical admissions
      ward of a teaching hospital. SAMPLE: 3228 emergency requests for biochemistry
      tests sent from the accident and emergency department and 1836 from the medical
      admissions ward during August 1999 to January 2000 when there was no recorded
      telephone contact for results. MAIN OUTCOME MEASURES: Proportion of emergency
      biochemistry results accessed via a ward terminal within 1 or 3 hours of becoming
      available and the proportion never seen by this means. RESULTS: The results from
      1443/3228 (45%) of urgent requests from accident and emergency and 529/1836 (29%)
      from the admissions ward were never accessed via the ward terminal. Results from
      794/3228 (25%) of accident and emergency requests and 413/1836 (22%) of
      admissions ward requests were seen within 1 hour of becoming available while a
      further 491/3228 (15%) and 341/1836 (19%) respectively were accessed between 1
      and 3 hours. In up to 43/1443 (3%) of the accident and emergency test results
      that were never looked at the findings might have led to an immediate change in
      patient management. CONCLUSIONS: When used as the sole substitute for telephoning
      results, the provision of terminal access to laboratory results on wards can
      hinder rather than promote the communication of emergency blood results to
      healthcare staff.

PMID- 11337443
TI  - Effect of increasing age on cataract surgery outcomes in very elderly patients.

PMID- 11337444
TI  - What are the elements of good treatment for hypertension?

PMID- 11337446
TI  - ABC of hypertension. Blood pressure measurement. Part III-automated
      sphygmomanometry: ambulatory blood pressure measurement.

PMID- 11337448
TI  - Checklists for improving rigour in qualitative research: a case of the tail
      wagging the dog?

PMID- 11337449
TI  - Should Nottingham University give back its tobacco money?

PMID- 11337454
TI  - Consent to cancer registration--an unnecessary burden.

PMID- 11337456
TI  - Internet therapy.

PMID- 11337460
TI  - Unlimited access--limitless success.

PMID- 11337461
TI  - Contemplating the end of the beginning.

PMID- 11337462
TI  - The human genome sequence expedition: views from the "base camp".

PMID- 11337463
TI  - Segmental duplications: what's missing, misassigned, and misassembled--and should
      we care?

PMID- 11337464
TI  - Through the lens of the sequence.

PMID- 11337465
TI  - Are we polyploids? A brief history of one hypothesis.

PMID- 11337466
TI  - Complete DNA sequence of Lactococcus lactis adds flavor to genomics.

PMID- 11337468
TI  - The complete human olfactory subgenome.
AB  - Olfactory receptors likely constitute the largest gene superfamily in the
      vertebrate genome. Here we present the nearly complete human olfactory subgenome
      elucidated by mining the genome draft with gene discovery algorithms. Over 900
      olfactory receptor genes and pseudogenes (ORs) were identified, two-thirds of
      which were not annotated previously. The number of extrapolated ORs is in good
      agreement with previous theoretical predictions. The sequence of at least 63% of
      the ORs is disrupted by what appears to be a random process of pseudogene
      formation. ORs constitute 17 gene families, 4 of which contain more than 100
      members each. "Fish-like" Class I ORs, previously considered a relic in higher
      tetrapods, constitute as much as 10% of the human repertoire, all in one large
      cluster on chromosome 11. Their lower pseudogene fraction suggests a functional
      significance. ORs are disposed on all human chromosomes except 20 and Y, and
      nearly 80% are found in clusters of 6-138 genes. A novel comparative cluster
      analysis was used to trace the evolutionary path that may have led to OR
      proliferation and diversification throughout the genome. The results of this
      analysis suggest the following genome expansion history: first, the generation of
      a "tetrapod-specific" Class II OR cluster on chromosome 11 by local duplication,
      then a single-step duplication of this cluster to chromosome 1, and finally an
      avalanche of duplication events out of chromosome 1 to most other chromosomes.
      The results of the data mining and characterization of ORs can be accessed at the
      Human Olfactory Receptor Data Exploratorium Web site
      (http://bioinfo.weizmann.ac.il/HORDE).

PMID- 11337469
TI  - Whole proteome pI values correlate with subcellular localizations of proteins for
      organisms within the three domains of life.
AB  - Isoelectric point (pI) values have long been a standard measure for
      distinguishing between proteins. This article analyzes distributions of pI values
      estimated computationally for all predicted ORFs in a selection of fully
      sequenced genomes. Histograms of pI values confirm the bimodality that has been
      observed previously for bacterial and archaeal genomes () and reveal a
      trimodality in eukaryotic genomes. A similar analysis on subsets of a
      nonredundant protein sequence database generated from the full database by
      selecting on subcellular localization shows that sequences annotated as
      corresponding to cytosolic and integral membrane proteins have pI distributions
      that appear to correspond with the two observed modes of bacteria and archaea.
      Furthermore, nuclear proteins have a broader distribution that may account for
      the third mode observed in eukaryotes. On the basis of this association between
      pI and subcellular localization, we conclude that the bimodal character of whole
      proteome pI values in bacteria and archaea and the trimodal character in
      eukaryotes are likely to be general properties of proteomes and are associated
      with the need for different pI values depending on subcellular localization. Our
      analyses also suggest that the proportions of proteomes consisting of membrane
      associated proteins may be currently underestimated.

PMID- 11337470
TI  - From first base: the sequence of the tip of the X chromosome of Drosophila
      melanogaster, a comparison of two sequencing strategies.
AB  - We present the sequence of a contiguous 2.63 Mb of DNA extending from the tip of
      the X chromosome of Drosophila melanogaster. Within this sequence, we predict 277
      protein coding genes, of which 94 had been sequenced already in the course of
      studying the biology of their gene products, and examples of 12 different
      transposable elements. We show that an interval between bands 3A2 and 3C2,
      believed in the 1970s to show a correlation between the number of bands on the
      polytene chromosomes and the 20 genes identified by conventional genetics, is
      predicted to contain 45 genes from its DNA sequence. We have determined the
      insertion sites of P-elements from 111 mutant lines, about half of which are in a
      position likely to affect the expression of novel predicted genes, thus
      representing a resource for subsequent functional genomic analysis. We compare
      the European Drosophila Genome Project sequence with the corresponding part of
      the independently assembled and annotated Joint Sequence determined through
      "shotgun" sequencing. Discounting differences in the distribution of known
      transposable elements between the strains sequenced in the two projects, we
      detected three major sequence differences, two of which are probably explained by
      errors in assembly; the origin of the third major difference is unclear. In
      addition there are eight sequence gaps within the Joint Sequence. At least six of
      these eight gaps are likely to be sites of transposable elements; the other two
      are complex. Of the 275 genes in common to both projects, 60% are identical
      within 1% of their predicted amino-acid sequence and 31% show minor differences
      such as in choice of translation initiation or termination codons; the remaining
      9% show major differences in interpretation.

PMID- 11337471
TI  - The complete genome sequence of the lactic acid bacterium Lactococcus lactis ssp.
      lactis IL1403.
AB  - Lactococcus lactis is a nonpathogenic AT-rich gram-positive bacterium closely
      related to the genus Streptococcus and is the most commonly used cheese starter.
      It is also the best-characterized lactic acid bacterium. We sequenced the genome
      of the laboratory strain IL1403, using a novel two-step strategy that comprises
      diagnostic sequencing of the entire genome and a shotgun polishing step. The
      genome contains 2,365,589 base pairs and encodes 2310 proteins, including 293
      protein-coding genes belonging to six prophages and 43 insertion sequence (IS)
      elements. Nonrandom distribution of IS elements indicates that the chromosome of
      the sequenced strain may be a product of recent recombination between two closely
      related genomes. A complete set of late competence genes is present, indicating
      the ability of L. lactis to undergo DNA transformation. Genomic sequence revealed
      new possibilities for fermentation pathways and for aerobic respiration. It also
      indicated a horizontal transfer of genetic information from Lactococcus to gram
      negative enteric bacteria of Salmonella-Escherichia group.

PMID- 11337473
TI  - Ancient genome duplications did not structure the human Hox-bearing chromosomes.
AB  - The fact that there are four homeobox (Hox) clusters in most vertebrates but only
      one in invertebrates is often cited as evidence for the hypothesis that two
      rounds of genome duplication by polyploidization occurred early in vertebrate
      history. In addition, it has been observed in humans and other mammals that
      numerous gene families include paralogs on two or more of the four Hox-bearing
      chromosomes (the chromosomes bearing the Hox clusters; i.e., human chromosomes 2,
      7, 12, and 17), and the existence of these paralogs has been taken as evidence
      that these genes were duplicated along with the Hox clusters by polyploidization.
      We tested this hypothesis by phylogenetic analysis of 42 gene families including
      members on two or more of the human Hox-bearing chromosomes. In 32 of these
      families there was evidence against the hypothesis that gene duplication occurred
      simultaneously with duplication of the Hox clusters. Phylogenies of 14 families
      supported the occurrence of one or more gene duplications before the origin of
      vertebrates, and of 15 gene duplication times estimated for gene families
      evolving in a clock-like manner, only six were dated to the same time period
      early in vertebrate history during which the Hox clusters duplicated.
      Furthermore, of gene families duplicated around the same time as the Hox
      clusters, the majority showed topologies inconsistent with their having
      duplicated simultaneously with the Hox clusters. The results thus indicate that
      ancient events of genome duplication, if they occurred at all, did not play an
      important role in structuring the mammalian Hox-bearing chromosomes.

PMID- 11337472
TI  - The basic helix-loop-helix protein family: comparative genomics and phylogenetic
      analysis.
AB  - The basic Helix-Loop-Helix (bHLH) proteins are transcription factors that play
      important roles during the development of various metazoans including fly,
      nematode, and vertebrates. They are also involved in human diseases, particularly
      in cancerogenesis. We made an extensive search for bHLH sequences in the
      completely sequenced genomes of Caenorhabditis elegans and of Drosophila
      melanogaster. We found 35 and 56 different genes, respectively, which may
      represent the complete set of bHLH of these organisms. A phylogenetic analysis of
      these genes, together with a large number (>350) of bHLH from other sources, led
      us to define 44 orthologous families among which 36 include bHLH from animals
      only, and two have representatives in both yeasts and animals. In addition, we
      identified two bHLH motifs present only in yeast, and four that are present only
      in plants; however, the latter number is certainly an underestimate. Most animal
      families (35/38) comprise fly, nematode, and vertebrate genes, suggesting that
      their common ancestor, which lived in pre-Cambrian times (600 million years ago)
      already owned as many as 35 different bHLH genes.

PMID- 11337474
TI  - Euteleost fish genomes are characterized by expansion of gene families.
AB  - The presence of additional hox clusters in the zebrafish has led to the
      hypothesis that there was a whole genome duplication at the origin of modern
      fish. To investigate the generality of this assumption, we analyzed all available
      actinopterygian fish gene families, and sequenced nuclear receptors from diverse
      teleost fish. The origin and timing of duplications was systematically determined
      by phylogenetic analysis. More genes are indeed found in zebrafish than in mouse.
      This abundance is shared by all major groups of euteleost fish, but not by eels.
      Phylogenetic analysis shows that it may result from frequent independent
      duplications, rather than from an ancestral genome duplication. We predict two
      zebrafish paralogs for most mouse or human genes, thus expressing a note of
      caution in functional comparison of fish and mammalian genomes. Redundancy
      appears to be the rule in fish developmental genetics. Finally, our results imply
      that the outcome of genome projects cannot be extrapolated easily between fish
      species.

PMID- 11337476
TI  - Computational inference of homologous gene structures in the human genome.
AB  - With the human genome sequence approaching completion, a major challenge is to
      identify the locations and encoded protein sequences of all human genes. To
      address this problem we have developed a new gene identification algorithm,
      GenomeScan, which combines exon-intron and splice signal models with similarity
      to known protein sequences in an integrated model. Extensive testing shows that
      GenomeScan can accurately identify the exon-intron structures of genes in
      finished or draft human genome sequence with a low rate of false-positives.
      Application of GenomeScan to 2.7 billion bases of human genomic DNA identified at
      least 20,000-25,000 human genes out of an estimated 30,000-40,000 present in the
      genome. The results show an accurate and efficient automated approach for
      identifying genes in higher eukaryotic genomes and provide a first-level
      annotation of the draft human genome.

PMID- 11337475
TI  - Genomic anatomy of a premier major histocompatibility complex paralogous region
      on chromosome 1q21-q22.
AB  - Human chromosomes 1q21-q25, 6p21.3-22.2, 9q33-q34, and 19p13.1-p13.4 carry
      clusters of paralogous loci, to date best defined by the flagship 6p MHC region.
      They have presumably been created by two rounds of large-scale genomic
      duplications around the time of vertebrate emergence. Phylogenetically, the 1q21
      25 region seems most closely related to the 6p21.3 MHC region, as it is only the
      MHC paralogous region that includes bona fide MHC class I genes, the CD1 and MR1
      loci. Here, to clarify the genomic structure of this model MHC paralogous region
      as well as to gain insight into the evolutionary dynamics of the entire
      quadriplication process, a detailed analysis of a critical 1.7 megabase (Mb)
      region was performed. To this end, a composite, deep, YAC, BAC, and PAC contig
      encompassing all five CD1 genes and linking the centromeric +P5 locus to the
      telomeric KRTC7 locus was constructed. Within this contig a 1.1-Mb BAC and PAC
      core segment joining CD1D to FCER1A was fully sequenced and thoroughly analyzed.
      This led to the mapping of a total of 41 genes (12 expressed genes, 12 possibly
      expressed genes, and 17 pseudogenes), among which 31 were novel. The latter
      include 20 olfactory receptor (OR) genes, 9 of which are potentially expressed.
      Importantly, CD1, SPTA1, OR, and FCERIA belong to multigene families, which have
      paralogues in the other three regions. Furthermore, it is noteworthy that 12 of
      the 13 expressed genes in the 1q21-q22 region around the CD1 loci are
      immunologically relevant. In addition to CD1A-E, these include SPTA1, MNDA, IFI
      16, AIM2, BL1A, FY and FCERIA. This functional convergence of structurally
      unrelated genes is reminiscent of the 6p MHC region, and perhaps represents the
      emergence of yet another antigen presentation gene cluster, in this case
      dedicated to lipid/glycolipid antigens rather than antigen-derived peptides.

PMID- 11337477
TI  - Evaluation of gene-finding programs on mammalian sequences.
AB  - We present an independent comparative analysis of seven recently developed gene
      finding programs: FGENES, GeneMark.hmm, Genie, Genescan, HMMgene, Morgan, and
      MZEF. For evaluation purposes we developed a new, thoroughly filtered, and
      biologically validated dataset of mammalian genomic sequences that does not
      overlap with the training sets of the programs analyzed. Our analysis shows that
      the new generation of programs has substantially better results than the programs
      analyzed in previous studies. The accuracy of the programs was also examined as a
      function of various sequence and prediction features, such as G + C content of
      the sequence, length and type of exons, signal type, and score of the exon
      prediction. This approach pinpoints the strengths and weaknesses of each
      individual program as well as those of computational gene-finding in general. The
      dataset used in this analysis (HMR195) as well as the tables with the complete
      results are available at http://www.cs.ubc.ca/~rogic/evaluation/.

PMID- 11337478
TI  - Characterization of the genomic Xist locus in rodents reveals conservation of
      overall gene structure and tandem repeats but rapid evolution of unique sequence.
AB  - The Xist locus plays a central role in the regulation of X chromosome
      inactivation in mammals, although its exact mode of action remains to be
      elucidated. Evolutionary studies are important in identifying conserved genomic
      regions and defining their possible function. Here we report cloning, sequence
      analysis, and detailed characterization of the Xist gene from four closely
      related species of common vole (field mouse), Microtus arvalis. Our analysis
      reveals that there is overall conservation of Xist gene structure both between
      different vole species and relative to mouse and human Xist/XIST. Within
      transcribed sequence, there is significant conservation over five short regions
      of unique sequence and also over Xist-specific tandem repeats. The majority of
      unique sequences, however, are evolving at an unexpectedly high rate. This is
      also evident from analysis of flanking sequences, which reveals a very high rate
      of rearrangement and invasion of dispersed repeats. We discuss these results in
      the context of Xist gene function and evolution.

PMID- 11337479
TI  - Human-ovine comparative sequencing of a 250-kb imprinted domain encompassing the
      callipyge (clpg) locus and identification of six imprinted transcripts: DLK1,
      DAT, GTL2, PEG11, antiPEG11, and MEG8.
AB  - Two ovine BAC clones and a connecting long-range PCR product, jointly spanning
      approximately 250 kb and representing most of the MULGE5-OY3 marker interval
      known to contain the clpg locus, were completely sequenced. The resulting genomic
      sequence was aligned with its human ortholog and extensively annotated. Six
      transcripts, four of which were novel, were predicted to originate from within
      the analyzed region and their existence confirmed experimentally: DLK1, DAT,
      GTL2, PEG11, antiPEG11, and MEG8. RT-PCR experiments performed on a range of
      tissues sampled from an 8-wk-old animal demonstrated the preferential expression
      of all six transcripts in skeletal muscle, which suggests that they are under
      control of common regulatory elements. The six transcripts were also shown to be
      subject to parental imprinting: DLK1, DAT, and PEG11 were shown to be paternally
      expressed and GTL2, antiPEG11, and MEG8 to be maternally expressed.

PMID- 11337480
TI  - Predicting deleterious amino acid substitutions.
AB  - Many missense substitutions are identified in single nucleotide polymorphism
      (SNP) data and large-scale random mutagenesis projects. Each amino acid
      substitution potentially affects protein function. We have constructed a tool
      that uses sequence homology to predict whether a substitution affects protein
      function. SIFT, which sorts intolerant from tolerant substitutions, classifies
      substitutions as tolerated or deleterious. A higher proportion of substitutions
      predicted to be deleterious by SIFT gives an affected phenotype than
      substitutions predicted to be deleterious by substitution scoring matrices in
      three test cases. Using SIFT before mutagenesis studies could reduce the number
      of functional assays required and yield a higher proportion of affected
      phenotypes. may be used to identify plausible disease candidates among the SNPs
      that cause missense substitutions.

PMID- 11337481
TI  - Basecalling with LifeTrace.
AB  - A pivotal step in electrophoresis sequencing is the conversion of the raw,
      continuous chromatogram data into the actual sequence of discrete nucleotides, a
      process referred to as basecalling. We describe a novel algorithm for basecalling
      implemented in the program LifeTrace. Like Phred, currently the most widely used
      basecalling software program, LifeTrace takes processed trace data as input. It
      was designed to be tolerant to variable peak spacing by means of an improved peak
      detection algorithm that emphasizes local chromatogram information over global
      properties. LifeTrace is shown to generate high-quality basecalls and reliable
      quality scores. It proved particularly effective when applied to MegaBACE
      capillary sequencing machines. In a benchmark test of 8372 dye-primer MegaBACE
      chromatograms, LifeTrace generated 17% fewer substitution errors, 16% fewer
      insertion/deletion errors, and 2.4% more aligned bases to the finished sequence
      than did Phred. For two sets totaling 6624 dye-terminator chromatograms, the
      performance improvement was 15% fewer substitution errors, 10% fewer
      insertion/deletion errors, and 2.1% more aligned bases. The processing time
      required by LifeTrace is comparable to that of Phred. The predicted quality
      scores were in line with observed quality scores, permitting direct use for
      quality clipping and in silico single nucleotide polymorphism (SNP) detection.
      Furthermore, we introduce a new type of quality score associated with every
      basecall: the gap-quality. It estimates the probability of a deletion error
      between the current and the following basecall. This additional quality score
      improves detection of single basepair deletions when used for locating potential
      basecalling errors during the alignment. We also describe a new protocol for
      benchmarking that we believe better discerns basecaller performance differences
      than methods previously published.

PMID- 11337483
TI  - Directed gap closure in large-scale sequencing projects.
AB  - A problem in many sequencing projects is the final closure of gaps left in the
      clone libraries, which serve as templates for sequencing, because of uncloned or
      unclonable genomic areas. By use of the Xylella fastidiosa genome as a test
      system, we present here an approach to generate, in a directed manner, sequence
      information from those gaps. We suggest using the complete clone library as a
      competitor against the genomic DNA of interest in a subtractive hybridization
      procedure similar to representational difference analysis (RDA). The resulting
      sequence information can be used to screen selectively other clone resources or
      serve directly for gap closure.

PMID- 11337482
TI  - Gene structure prediction and alternative splicing analysis using genomically
      aligned ESTs.
AB  - With the availability of a nearly complete sequence of the human genome, aligning
      expressed sequence tags (EST) to the genomic sequence has become a practical and
      powerful strategy for gene prediction. Elucidating gene structure is a complex
      problem requiring the identification of splice junctions, gene boundaries, and
      alternative splicing variants. We have developed a software tool, Transcript
      Assembly Program (TAP), to delineate gene structures using genomically aligned
      EST sequences. TAP assembles the joint gene structure of the entire genomic
      region from individual splice junction pairs, using a novel algorithm that uses
      the EST-encoded connectivity and redundancy information to sort out the complex
      alternative splicing patterns. A method called polyadenylation site scan (PASS)
      has been developed to detect poly-A sites in the genome. TAP uses these
      predictions to identify gene boundaries by segmenting the joint gene structure at
      polyadenylated terminal exons. Reconstructing 1007 known transcripts, TAP scored
      a sensitivity (Sn) of 60% and a specificity (Sp) of 92% at the exon level. The
      gene boundary identification process was found to be accurate 78% of the time.
      also reports alternative splicing patterns in EST alignments. An analysis of
      alternative splicing in 1124 genic regions suggested that more than half of human
      genes undergo alternative splicing. Surprisingly, we saw an absolute majority of
      the detected alternative splicing events affect the coding region. Furthermore,
      the evolutionary conservation of alternative splicing between human and mouse was
      analyzed using an EST-based approach. (See http://stl.wustl.edu/~zkan/TAP/)

PMID- 11337467
TI  - Identification and characterization of the potential promoter regions of 1031
      kinds of human genes.
AB  - To understand the mechanism of transcriptional regulation, it is essential to
      identify and characterize the promoter, which is located proximal to the mRNA
      start site. To identify the promoters from the large volumes of genomic
      sequences, we used mRNA start sites determined by a large-scale sequencing of the
      cDNA libraries constructed by the "oligo-capping" method. We aligned the mRNA
      start sites with the genomic sequences and retrieved adjacent sequences as
      potential promoter regions (PPRs) for 1031 genes. The PPR sequences were searched
      to determine the frequencies of major promoter elements. Among 1031 PPRs, 329
      (32%) contained TATA boxes, 872 (85%) contained initiators, 999 (97%) contained
      GC box, and 663 (64%) contained CAAT box. Furthermore, 493 (48%) PPRs were
      located in CpG islands. This frequency of CpG islands was reduced in
      TATA(+)/Inr(+) PPRs and in the PPRs of ubiquitously expressed genes. In the PPRs
      of the CGM2 gene, the DRA gene, and the TM30pl genes, which showed highly colon
      specific expression patterns, the consensus sequences of E boxes were commonly
      observed. The PPRs were also useful for exploring promoter SNPs.

PMID- 11337484
TI  - Assembly, annotation, and integration of UNIGENE clusters into the human genome
      draft.
AB  - The recent release of the first draft of the human genome provides an
      unprecedented opportunity to integrate human genes and their functions in a
      complete positional context. However, at least three significant technical
      hurdles remain: first, to assemble a complete and nonredundant human transcript
      index; second, to accurately place the individual transcript indices on the human
      genome; and third, to functionally annotate all human genes. Here, we report the
      extension of the UNIGENE database through the assembly of its sequence clusters
      into nonredundant sequence contigs. Each resulting consensus was aligned to the
      human genome draft. A unique location for each transcript within the human genome
      was determined by the integration of the restriction fingerprint, assembled
      genomic contig, and radiation hybrid (RH) maps. A total of 59,500 UNIGENE
      clusters were mapped on the basis of at least three independent criteria as
      compared with the 30,000 human genes/ESTs currently mapped in Genemap'99.
      Finally, the extension of the human transcript consensus in this study enabled a
      greater number of putative functional assignments than the 11,000 annotated
      entries in UNIGENE. This study reports a draft physical map with annotations for
      a majority of the human transcripts, called the Human Index of Nonredundant
      Transcripts (HINT). Such information can be immediately applied to the discovery
      of new genes and the identification of candidate genes for positional cloning.

PMID- 11337485
TI  - Degradation of the Alzheimer's amyloid beta peptide by endothelin-converting
      enzyme.
AB  - Deposition of beta-amyloid (Abeta) peptides in the brain is an early and
      invariant feature of all forms of Alzheimer's disease. As with any secreted
      protein, the extracellular concentration of Abeta is determined not only by its
      production but also by its catabolism. A major focus of Alzheimer's research has
      been the elucidation of the mechanisms responsible for the generation of Abeta.
      Much less, however, is known about the mechanisms responsible for Abeta removal
      in the brain. In this report, we describe the identification of endothelin
      converting enzyme-1 (ECE-1) as a novel Abeta-degrading enzyme. We show that
      treatment of endogenous ECE-expressing cell lines with the metalloprotease
      inhibitor phosphoramidon causes a 2-3-fold elevation in extracellular Abeta
      concentration that appears to be due to inhibition of intracellular Abeta
      degradation. Furthermore, we show that overexpression of ECE-1 in Chinese hamster
      ovary cells, which lack endogenous ECE activity, reduces extracellular Abeta
      concentration by up to 90% and that this effect is completely reversed by
      treatment of the cells with phosphoramidon. Finally, we show that recombinant
      soluble ECE-1 is capable of hydrolyzing synthetic Abeta40 and Abeta42 in vitro at
      multiple sites.

PMID- 11337486
TI  - Characterization of the Drosophila caspase, DAMM.
AB  - Caspases are main effectors of apoptosis in metazoans. Genome analysis indicates
      that there are seven caspases in Drosophila, six of which have been previously
      characterized. Here we describe the cloning and characterization of the last
      Drosophila caspase, DAMM. Similar to mammalian effector caspases, DAMM lacks a
      long prodomain. We show that the DAMM precursor, along with the caspases DRONC
      and DECAY, is partially processed in cells undergoing apoptosis. Recombinant DAMM
      produced in Escherichia coli shows significant catalytic activity on a
      pentapeptide caspase substrate. Low levels of damm mRNA are ubiquitously
      expressed in Drosophila embryos during early stages of development. Relatively
      high levels of damm mRNA are detected in larval salivary glands and midgut, and
      in adult egg chambers. Ectopic expression of DAMM in cultured cells induces
      apoptosis, and similarly, transgenic overexpression of DAMM, but not of a
      catalytically inactive DAMM mutant, in Drosophila results in a rough eye
      phenotype. We demonstrate that expression of the catalytically inactive DAMM
      mutant protein significantly suppresses the rough eye phenotype due to the
      overexpression of HID, suggesting that DAMM may be required in a hid-mediated
      cell death pathway.

PMID- 11337487
TI  - Extensive repertoire of membrane-bound and soluble dendritic cell-specific ICAM-3
      grabbing nonintegrin 1 (DC-SIGN1) and DC-SIGN2 isoforms. Inter-individual
      variation in expression of DC-SIGN transcripts.
AB  - Expression in dendritic cells (DCs) of DC-SIGN, a type II membrane protein with a
      C-type lectin ectodomain, is thought to play an important role in establishing
      the initial contact between DCs and resting T cells. DC-SIGN is also a unique
      type of human immunodeficiency virus-1 (HIV-1) attachment factor and promotes
      efficient infection in trans of cells that express CD4 and chemokine receptors.
      We have identified another gene, designated here as DC-SIGN2, that exhibits high
      sequence homology with DC-SIGN. Here we demonstrate that alternative splicing of
      DC-SIGN1 (original version) and DC-SIGN2 pre-mRNA generates a large repertoire of
      DC-SIGN-like transcripts that are predicted to encode membrane-associated and
      soluble isoforms. The range of DC-SIGN1 mRNA expression was significantly broader
      than previously reported and included THP-1 monocytic cells, placenta, and
      peripheral blood mononuclear cells (PBMCs), and there was cell
      maturation/activation-induced differences in mRNA expression levels.
      Immunostaining of term placenta with a DC-SIGN1-specific antiserum showed that DC
      SIGN1 is expressed on endothelial cells and CC chemokine receptor 5 (CCR5)
      positive macrophage-like cells in the villi. DC-SIGN2 mRNA expression was high in
      the placenta and not detectable in PBMCs. In DCs, the expression of DC-SIGN2
      transcripts was significantly lower than that of DC-SIGN1. Notably, there was
      significant inter-individual heterogeneity in the repertoire of DC-SIGN1 and DC
      SIGN2 transcripts expressed. The genes for DC-SIGN1, DC-SIGN2, and CD23, another
      Type II lectin, colocalize to an approximately 85 kilobase pair region on
      chromosome 19p13.3, forming a cluster of related genes that undergo highly
      complex alternative splicing events. The molecular diversity of DC-SIGN-1 and -2
      is reminiscent of that observed for certain other adhesive cell surface proteins
      involved in cell-cell connectivity. The generation of this large collection of
      polymorphic cell surface and soluble variants that exhibit inter-individual
      variation in expression levels has important implications for the pathogenesis of
      HIV-1 infection, as well as for the molecular code required to establish complex
      interactions between antigen-presenting cells and T cells, i.e. the immunological
      synapse.

PMID- 11337489
TI  - Redox-sensitive transactivation of epidermal growth factor receptor by tumor
      necrosis factor confers the NF-kappa B activation.
AB  - Cross-communication between different signaling systems allows the integration of
      the great diversity of stimuli that a cell receives under varying physiological
      situations. In this paper we have explored the possibility that tumor necrosis
      factor (TNF) receptor signal cross-talks with epidermal growth factor (EGF)
      receptor signal on the nuclear factor-kappa B (NF-kappa B) activation pathway. We
      have demonstrated that overexpression of the EGF receptor (EGFR) in NIH3T3 cells
      significantly enhances TNF-induced NF-kappa B-dependent luciferase activity even
      without EGF, that EGF treatment has a synergistic effect on the induction of the
      reporter activity, and that this enhancement is suppressed by AG1478, EGFR
      specific tyrosine kinase inhibitor. We also have shown that TNF induces tyrosine
      phosphorylation and internalization of the overexpressed EGFR in NIH3T3 cells and
      the endogenously expressed EGFR in A431 cells and that the transactivation by TNF
      is suppressed by N-acetyl-l-cysteine or overexpression of an endogenous reducing
      molecule, thioredoxin, but not by phosphatidylinositol 3-kinase inhibitors and
      protein kinase C inhibitor. Taken together, this evidence strongly suggests that
      EGFR transactivation by TNF, which is regulated in a redox-dependent manner, is
      playing a pivotal role in TNF-induced NF-kappa B activation.

PMID- 11337488
TI  - Addition of a glycophosphatidylinositol to acetylcholinesterase. Processing,
      degradation, and secretion.
AB  - We introduced various mutations and modifications in the GPI anchoring signal of
      rat acetylcholinesterase (AChE). 1) The resulting mutants, expressed in
      transiently transfected COS cells, were initially produced at the same rate, in
      an active form, but the fraction of GPI-anchored AChE and the steady state level
      of AChE activity varied over a wide range. 2) Productive interaction with the GPI
      addition machinery led to GPI anchoring, secretion of uncleaved protein, and
      secretion of a cleaved protein, in variable proportions. Unproductive interaction
      led to degradation; poorly processed molecules were degraded rather than retained
      intracellularly or secreted. 3) An efficient glypiation appeared necessary but
      not sufficient for a high level of secretion; the cleaved, secreted protein was
      possibly generated as a by-product of transamidation. 4) Glypiation was
      influenced by a wider context than the triplet omega/omega + 1/omega + 2,
      particularly omega - 1. 5) Glypiation was not affected by the closeness of the
      omega site to the alpha(10) helix of the catalytic domain. 6) A cysteine could
      simultaneously form a disulfide bond and serve as an omega site; however, there
      was a mutual interference between glypiation and the formation of an
      intercatenary disulfide bond, at a short distance upstream of omega. 7)
      Glypiation was not affected by the presence of an N-glycosylation site at omega
      or in its vicinity or by the addition of a short hydrophilic, highly charged
      peptide (FLAG; DYKDDDDK) at the C terminus of the hydrophobic region.

PMID- 11337490
TI  - Inhibition of the catalytic activity of cell adhesion kinase beta by protein
      tyrosine phosphatase-PEST-mediated dephosphorylation.
AB  - Protein-tyrosine phosphatase (PTP)-PEST is a cytoplasmic tyrosine phosphatase
      that can bind and dephosphorylate the focal adhesion-associated proteins
      p130(CAS) and paxillin. Focal adhesion kinase (FAK) and cell adhesion kinase beta
      (CAKbeta)/PYK2/CADTK/RAFTK are protein-tyrosine kinases that can colocalize with,
      bind to, and induce tyrosine phosphorylation of p130(CAS) and paxillin. Thus, we
      considered the possibility that these kinases might be substrates for PTP-PEST.
      Using a combination of substrate-trapping assays and overexpression of PTP-PEST
      in mammalian cells, CAKbeta was found to be a substrate for PTP-PEST. Both the
      major autophosphorylation site of CAKbeta (Tyr(402)) and activation loop tyrosine
      residues, Tyr(579) and Tyr(580), were targeted for dephosphorylation by PTP-PEST.
      Dephosphorylation of CAKbeta by PTP-PEST dramatically inhibited CAKbeta kinase
      activity. In contrast, FAK was a poor substrate for PTP-PEST, and treatment with
      PTP-PEST had no effect on FAK kinase activity. Tyrosine phosphorylation of
      paxillin, which is greatly enhanced by CAKbeta overexpression, was dramatically
      reduced upon coexpression of PTP-PEST. Finally, endogenous PTP-PEST and
      endogenous CAKbeta were found to localize to similar cellular compartments in
      epithelial and smooth muscle cells. These results suggest that CAKbeta is a
      substrate of PTP-PEST and that FAK is a poor PTP-PEST substrate. Further, PTP
      PEST can negatively regulate CAKbeta signaling by inhibiting the catalytic
      activity of the kinase.

PMID- 11337491
TI  - Muscarinic receptor stimulation induces translocation of an alpha-synuclein
      oligomer from plasma membrane to a light vesicle fraction in cytoplasm.
AB  - The close correspondence between the distribution of brain alpha-synuclein and
      that of muscarinic M1 and M3 receptors suggests a role for this protein in
      cholinergic transmission. We thus examined the effect of muscarinic stimulation
      on alpha-synuclein in SH-SY5Y, a human dopaminergic cell line that expresses this
      protein. Under basal conditions, alpha-synuclein was detected in all subcellular
      compartments isolated as follows: plasma membrane, cytoplasm, nucleus, and two
      vesicle fractions. The lipid fractions contained only a 45-kDa alpha-synuclein
      oligomer, whereas the cytoplasmic and nuclear fractions contained both the
      oligomer and the monomer. This finding suggests alpha-synuclein exists
      physiologically as a lipid-bound oligomer and a soluble monomer. Muscarinic
      stimulation by carbachol reduced the alpha-synuclein oligomer in plasma membrane
      over a 30-min period, with a concomitant increase of both the oligomer and the
      monomer in the cytoplasmic fraction. The oligomer was associated with a light
      vesicle fraction in cytoplasm that contains uncoated endocytotic vesicles. The
      carbachol-induced alteration of alpha-synuclein was blocked by atropine.
      Translocation of the alpha-synuclein oligomer in response to carbachol
      stimulation corresponds closely with the time course of ligand-stimulated
      muscarinic receptor endocytosis. The data suggest that the muscarine receptor
      stimulated release of the alpha-synuclein oligomer from plasma membrane, and its
      subsequent association with the endocytotic vesicle fraction may have a role in
      muscarine receptor endocytosis. We propose that its function may be a transient
      release of membrane-bound phospholipase D2 from alpha-synuclein inhibition, thus
      allowing this lipase to participate in muscarinic receptor endocytosis.

PMID- 11337492
TI  - Dbl and the Rho GTPases activate NF kappa B by I kappa B kinase (IKK)-dependent
      and IKK-independent pathways.
AB  - Dbl is a guanine nucleotide exchange factor that activates the Rho family GTPases
      Cdc42, Rac, and Rho. Dbl and all three GTPases are strong activators of
      transcription factor NF kappa B, which has been shown to have an important role
      in Dbl-induced oncogenic transformation. Here we show that although Dbl
      activation of NF kappa B requires Cdc42, Rac, and Rho, the different GTPases
      activate NF kappa B by different mechanisms. Whereas Rac stimulates the activity
      of the I kappa B kinase IKK beta, Cdc42 and Rho activate NF kappa B without
      activating either IKK alpha or IKK beta. Like Dbl, Rac activation of IKK beta is
      mediated by the serine/threonine kinases NIK but not MEKK. This differs from Rac
      activation of the JNK pathway, which was previously shown to be mediated by MEKK.
      The pathway leading from Rho and Cdc42 to NF kappa B is more elusive, but our
      results suggest that it involves an IKK alpha/IKK beta-independent mechanism.
      Finally, we show that the signaling enzymes that mediate NF kappa B activation by
      Dbl and the Rho GTPases are also necessary for malignant transformation induced
      by oncogenic Dbl.

PMID- 11337493
TI  - Identification and characterization of the prolactin-binding protein in human
      serum and milk.
AB  - The actions of prolactin (PRL) are mediated by its receptor, a member of the
      superfamily of single transmembrane cytokine receptors. High affinity binding
      proteins for the closely related growth hormone have been found in the sera of
      several species including humans and are generated by alternative splicing or
      proteolysis of the growth hormone receptor extracellular domain (ECD). In
      contrast, no conclusive evidence has been presented that an analogous prolactin
      binding protein (PRLBP) is expressed in human serum. Using both monoclonal and
      polyclonal antibodies generated against hPRL and the ECD of the human prolactin
      receptor, co-immunoprecipitation analyses of human serum identified a 32-kDa
      hPRLBP capable of binding both hPRL and human growth hormone. A measurable
      fraction of circulating PRL (36%) was associated with the hPRLBP. Despite well
      documented sex differences in serum hPRL levels, there were no significant
      differences in the levels of hPRLBP found in the sera of normal adult males and
      females (15.3 +/- 1.3 ng/ml versus 13.4 +/- 0.8 ng/ml, respectively (mean +/-
      S.E.)). Immunoprecipitation studies also detected the PRLBP in human milk albeit
      at lower concentrations than found in sera. Deglycosylation did not alter its
      electrophoretic mobility, indicating an absence of carbohydrate moieties and
      suggesting that the hPRLBP spans most of the PRLR ECD, a result confirmed by
      limited proteolysis and mass spectrometry. The potential function of this serum
      chaperone was assessed in vitro by the addition of recombinant hPRLBP to the
      culture medium of the PRL-dependent Nb2 T-cell line. These studies revealed that
      the hPRLBP antagonizes PRL action, inhibiting PRL-driven growth in a dose
      dependent manner.

PMID- 11337494
TI  - The lectin chaperone calnexin utilizes polypeptide-based interactions to
      associate with many of its substrates in vivo.
AB  - Calnexin and calreticulin are molecular chaperones of the endoplasmic reticulum
      that bind to newly synthesized glycoproteins in part through a lectin site
      specific for monoglucosylated (Glc(1)Man(7-9)GlcNAc(2)) oligosaccharides. In
      addition to this lectin-oligosaccharide interaction, in vitro studies have
      demonstrated that calnexin and calreticulin can bind to polypeptide segments of
      both glycosylated and nonglycosylated proteins. However, the in vivo relevance of
      this latter interaction has been questioned. We examined whether polypeptide
      based interactions occur between calnexin and its substrates in vivo using the
      glucosidase inhibitor castanospermine or glucosidase-deficient cells to prevent
      the formation of monoglucosylated oligosaccharides. We show that if care is taken
      to preserve weak interactions, the block in lectin-oligosaccharide binding leads
      to the loss of some calnexin-substrate complexes, but many others remain readily
      detectable. Furthermore, we demonstrate that calnexin is capable of associating
      in vivo with a substrate that completely lacks Asn-linked oligosaccharides. The
      binding of calnexin to proteins that lack monoglucosylated oligosaccharides could
      not be attributed to nonspecific adsorption nor to its inclusion in protein
      aggregates. We conclude that both lectin-oligosaccharide and polypeptide-based
      interactions occur between calnexin and diverse proteins in vivo and that the
      strength of the latter interaction varies substantially between protein
      substrates.

PMID- 11337495
TI  - Tyrosine phosphorylation of p85 relieves its inhibitory activity on
      phosphatidylinositol 3-kinase.
AB  - Under resting conditions, the p85 regulatory subunit of phosphatidylinositol 3
      kinase (PI3K) serves to both stabilize and inactivate the p110 catalytic subunit.
      The inhibitory activity of p85 is relieved by occupancy of the NH(2)-terminal SH2
      domain of p85 by phosphorylated tyrosine. Src family kinases phosphorylate
      tyrosine 688 in p85, a process that we have shown to be reversed by the activity
      of the p85-associated SH2 domain-containing phosphatase SHP1. We demonstrate that
      phosphorylation of the downstream PI3K target Akt is increased in cells lacking
      SHP1, implicating phosphorylation of p85 in the regulation of PI3K activity.
      Furthermore, the in vitro specific activity of PI3K associated with tyrosine-
      phosphorylated p85 is higher than that associated with nonphosphorylated p85.
      Expression of wild-type p85 inhibits PI3K enzyme activity as indicated by PI3K-
      dependent Akt phosphorylation. The inhibitory activity of p85 is accentuated by
      mutation of tyrosine 688 to alanine and reversed by mutation of tyrosine 688 to
      aspartic acid, changes that block and mimic tyrosine phosphorylation,
      respectively Strikingly, mutation of tyrosine 688 to aspartic acid completely
      reverses the inhibitory activity of p85 on cell viability and activation of the
      downstream targets Akt and NFkappaB, indicative of the physiological relevance of
      p85 phosphorylation. Tyrosine phosphorylation of Tyr(688) or mutation of tyrosine
      688 to aspartic acid is sufficient to allow binding to the NH(2)-terminal SH2
      domain of p85. Thus an intramolecular interaction between phosphorylated Tyr(688)
      and the NH(2)-terminal SH2 domain of p85 can relieve the inhibitory activity of
      p85 on p110. Taken together, the data indicate that phosphorylation of Tyr(688)
      in p85 leads to a novel mechanism of PI3K regulation.

PMID- 11337496
TI  - Insulin/insulin-like growth factor-I and estrogen cooperate to stimulate cyclin E
      Cdk2 activation and cell Cycle progression in MCF-7 breast cancer cells through
      differential regulation of cyclin E and p21(WAF1/Cip1).
AB  - Estrogens and insulin/insulin-like growth factor-I (IGF-I) are potent mitogens
      for breast epithelial cells and, when co-administered, induce synergistic
      stimulation of cell proliferation. To investigate the molecular basis of this
      effect, a MCF-7 breast cancer cell model was established where serum deprivation
      and concurrent treatment with the pure estrogen antagonist, ICI 182780, inhibited
      growth factor and estrogen action and arrested cells in G(0)/G(1) phase.
      Subsequent stimulation with insulin or IGF-I alone failed to induce significant S
      phase entry. However, these treatments increased cyclin D1, cyclin E, and p21
      gene expression and induced the formation of active Cdk4 complexes but resulted
      in only minor increases in cyclin E-Cdk2 activity, likely due to recruitment of
      the cyclin-dependent kinase (CDK) inhibitor p21(WAF1/Cip1) into these complexes.
      Treatment with estradiol alone resulted in a greater increase in cyclin D1 gene
      expression but markedly decreased p21 expression, with a concurrent increase in
      Cdk4 and Cdk2 activity and subsequent synchronous entry of cells into S phase. Co
      administration of insulin/IGF-I and estrogen induced synergistic stimulation of S
      phase entry coincident with synergistic activation of high molecular mass
      (approximately 350 kDa) cyclin E-Cdk2 complexes lacking p21. To determine if the
      ability of estrogen to deplete p21 was central to these effects, cells stimulated
      with insulin and estradiol were infected with an adenovirus expressing p21.
      Induction of p21 to levels equivalent to those following treatment with insulin
      alone markedly inhibited the synergism between estradiol and insulin on S-phase
      entry. Thus the ability of estradiol to antagonize the insulin-induced increase
      in p21 gene expression, with consequent activation of cyclin E-Cdk2, is a central
      component of the synergistic stimulation of breast epithelial cell proliferation
      induced by simultaneous activation of the estrogen and insulin/IGF-I signaling
      pathways.

PMID- 11337497
TI  - Inositol hexakisphosphate kinase 2 mediates growth suppressive and apoptotic
      effects of interferon-beta in ovarian carcinoma cells.
AB  - Interferons (IFNs) regulate the expression of genes that mediate their antiviral,
      antitumor, and immunomodulatory actions. We have previously shown that IFN-beta
      suppresses growth of human ovarian carcinoma xenografts in vivo and induces
      apoptosis of ovarian carcinoma cells in vitro. To investigate mechanisms of IFN
      beta-induced apoptosis we employed an antisense technical knockout approach to
      identify gene products that mediate cell death and have isolated several
      regulators of interferon-induced death (RIDs). In this investigation, we have
      characterized one of the RIDs, RID-2. Sequence analysis revealed that RID-2 was
      identical to human inositol hexakisphosphate kinase 2 (IP6K2). IP6K2 is post
      transcriptionally induced by IFN-beta in ovarian carcinoma cells. A mutant IP6K2
      with substitutions in the putative inositol phosphate binding domain abrogates
      IFN-beta-induced apoptosis. These studies identify a novel function for IP6K2 in
      cell growth regulation and apoptosis.

PMID- 11337498
TI  - Lithium inhibits cell cycle progression and induces stabilization of p53 in
      bovine aortic endothelial cells.
AB  - Lithium affects development of various organisms and cell fate through the
      inhibition of glycogen synthase kinase-3 beta and induction of the Wnt/beta
      catenin signaling pathway. In this study, we investigated the effects of lithium
      on primary bovine aortic endothelial cells (BAEC). Lithium treatment of BAEC
      induced beta-catenin stabilization but failed to activate the transcriptional
      activity of the beta-catenin/T-cell factor complex. Lithium caused a sustained
      G(2)/M cell cycle arrest without affecting cell viability. Reversibility of this
      cell cycle arrest occurred up to 3 days after treatment but was reduced
      thereafter. Lithium-treated BAEC exhibited a senescent-like morphology with an
      increase in cells positive for the senescence-associated-beta-galactosidase
      activity. Lithium also increased the expression of p21(Cip), a cyclin-dependent
      kinase inhibitor, both at the protein and RNA levels. No change in p21(Cip) mRNA
      stability was observed, whereas the transcriptional activity of a p21(Cip)
      promoter-luciferase construct containing p53 binding sites was increased after
      lithium treatment. Furthermore, lithium caused increased transcription of a
      reporter gene under the control of a promoter containing the p53 consensus
      binding sites both in transiently transfected BAEC and in a stably transfected
      fibroblast cell line. Lithium caused accumulation of p53 protein in BAEC without
      affecting p53 mRNA levels. Finally, up-regulation of p21(Cip) in response to
      lithium did not occur in mouse embryonic fibroblasts that were null for p53
      alleles, confirming the dependence on a p53 pathway for this lithium effect.
      These findings demonstrate for the first time that lithium induces also
      stabilization of the tumor suppressor p53 and reveal a new mechanism that may
      contribute to the neuroprotective effects of lithium.

PMID- 11337499
TI  - JunD regulates transcription of the tissue inhibitor of metalloproteinases-1 and
      interleukin-6 genes in activated hepatic stellate cells.
AB  - Activation of hepatic stellate cells (HSCs) to a myofibroblast-like phenotype is
      the pivotal event in hepatic wound healing and fibrosis. Rat HSCs activated in
      vitro express JunD, Fra2, and FosB as the predominant AP-1 DNA-binding proteins,
      and all three associate with an AP-1 sequence that is essential for activity of
      the tissue inhibitor of metalloproteinases-1 (TIMP-1) promoter. In this study, we
      used expression vectors for wild-type, dominant-negative, and forced homodimeric
      (Jun/eb1 chimeric factors) forms of JunD and other Fos and Jun proteins to
      determine the requirement for JunD in the transcriptional regulation of the TIMP
      1 and interleukin-6 (IL-6) genes. JunD activity was required for TIMP-1 gene
      promoter activity, whereas overexpression of Fra2 or FosB caused a repression of
      promoter activity. The ability of homodimeric JunD/eb1 to elevate TIMP-1 promoter
      activity supports a role for JunD homodimers as the major AP-1-dependent
      transactivators of the TIMP-1 gene. IL-6 promoter activity was induced upon
      activation of HSCs and also required JunD activity; however, expression of
      JunD/eb1 homodimers resulted in transcriptional repression. Mutagenesis of the IL
      6 promoter showed that an AP-1 DNA-binding site previously reported to be an
      activator of transcription in fibroblasts functions as a suppressor of promoter
      activity in HSCs. We conclude that JunD activates IL-6 gene transcription as a
      heterodimer and operates at an alternative DNA-binding site in the promoter. The
      relevance of these findings to events occurring in the injured liver was
      addressed by showing that AP-1 DNA-binding complexes are induced during HSC
      activation and contain JunD as the predominant Jun family protein. JunD is
      therefore an important transcriptional regulator of genes responsive to Jun homo-
      and heterodimers in activated HSCs.

PMID- 11337500
TI  - Direct identification of human oxytocin receptor-binding domains using a
      photoactivatable cyclic peptide antagonist: comparison with the human V1a
      vasopressin receptor.
AB  - Understanding of the molecular determinants responsible for antagonist binding to
      the oxytocin receptor should provide important insights that facilitate rational
      design of potential therapeutic agents for the treatment of preterm labor. To
      study ligand/receptor interactions, we used a novel photosensitive radioiodinated
      antagonist of the human oxytocin receptor, d(CH(2))(5)
      [Tyr(Me)(2),Thr(4),Orn(8),Phe(3(125)I,4N(3))-NH(2)9]vasotocin. This ligand had an
      equivalent high affinity for human oxytocin and V(1a) vasopressin receptors
      expressed in Chinese hamster ovary cells. Taking advantage of this dual
      specificity, we conducted photoaffinity labeling experiments on both receptors.
      Photolabeled oxytocin and V(1a) receptors appeared as a unique protein band at 70
      75 kDa and two labeled protein bands at 85-90 and 46 kDa, respectively. To
      identify contact sites between the antagonist and the receptors, the labeled 70
      75- and the 46-kDa proteins were cleaved with CNBr and digested with Lys-C and
      Arg-C endoproteinases. The fragmentation patterns allowed the identification of a
      covalently labeled region in the oxytocin receptor transmembrane domain III
      consisting of the residues Leu(114)-Val(115)-Lys(116). Analysis of contact sites
      in the V(1a) receptor led to the identification of the homologous region
      consisting of the residues Val(126)-Val(127)-Lys(128). Binding domains were
      confirmed by mutation of several CNBr cleavage sites in the oxytocin receptor and
      of one Lys-C cleavage site in the V(1a) receptor. The results are in agreement
      with previous experimental data and three-dimensional models of agonist and
      antagonist binding to members of the oxytocin/vasopressin receptor family.

PMID- 11337501
TI  - Binding of double-stranded RNA to protein kinase PKR is required for dimerization
      and promotes critical autophosphorylation events in the activation loop.
AB  - Protein kinase PKR is activated by double-stranded RNA (dsRNA) and phosphorylates
      translation initiation factor 2alpha to inhibit protein synthesis in virus
      infected mammalian cells. PKR contains two dsRNA binding motifs (DRBMs I and II)
      required for activation by dsRNA. There is strong evidence that PKR activation
      requires dimerization, but the role of dsRNA in dimer formation is controversial.
      By making alanine substitutions predicted to remove increasing numbers of side
      chain contacts between the DRBMs and dsRNA, we found that dimerization of full
      length PKR in yeast was impaired by the minimal combinations of mutations
      required to impair dsRNA binding in vitro. Mutation of Ala-67 to Glu in DRBM-I,
      reported to abolish dimerization without affecting dsRNA binding, destroyed both
      activities in our assays. By contrast, deletion of a second dimerization region
      that overlaps the kinase domain had no effect on PKR dimerization in yeast. Human
      PKR contains at least 15 autophosphorylation sites, but only Thr-446 and Thr-451
      in the activation loop were found here to be critical for kinase activity in
      yeast. Using an antibody specific for phosphorylated Thr-451, we showed that Thr
      451 phosphorylation is stimulated by dsRNA binding. Our results provide strong
      evidence that dsRNA binding is required for dimerization of full-length PKR
      molecules in vivo, leading to autophosphorylation in the activation loop and
      stimulation of the eIF2alpha kinase function of PKR.

PMID- 11337502
TI  - Yeast 1,3-beta-glucan synthase activity is inhibited by phytosphingosine
      localized to the endoplasmic reticulum.
AB  - 1,3-beta-D-Glucan, a major filamentous component of the cell wall in the budding
      yeast Saccharomyces cerevisiae, is synthesized by 1,3-beta-glucan synthase (GS).
      Although a yeast gene whose product is required for GS activity in vitro, GNS1,
      was isolated and characterized, its role in GS function has remained unknown. In
      the current study we show that Deltagns1 cells accumulate a non-competitive and
      non-proteinous inhibitor(s) in the membrane fraction. Investigations of
      inhibitory activity on GS revealed that the inhibitor(s) is mainly present in the
      sphingolipid fraction. It is shown that Deltagns1 cells contain phytosphingosine
      (PHS), an intermediate in the sphingolipid biosynthesis, 30-fold more than wild
      type cells do. The membrane fraction isolated from Deltasur2 cells contains an
      increased amount of dihydrosphingosine (DHS) and also exhibits reduced GS
      activity. Among constituents of the sphingolipid fraction, PHS and DHS show
      striking inhibition in a non-competitive manner. The intracellular level of DHS
      is much lower than that of PHS in wild-type cells, suggesting that PHS is the
      primary inhibitor of GS in vivo. The localization of PHS to the endoplasmic
      reticulum in wild-type cells coincides with that of the inhibitor(s) in Deltagns1
      cells. Taken together, our results indicate that PHS is a potent inhibitor of
      yeast GS in vivo.

PMID- 11337503
TI  - Requirement for yeast TAF145 function in transcriptional activation of the RPS5
      promoter that depends on both core promoter structure and upstream activating
      sequences.
AB  - The general transcription factor TFIID has been shown to be involved in both core
      promoter recognition and the transcriptional activation of eukaryotic genes. We
      recently isolated TAF145 (one of TFIID subunits) temperature-sensitive mutants in
      yeast, in which transcription of the TUB2 gene is impaired at restrictive
      temperatures due to a defect in core promoter recognition. Here, we show in these
      mutants that the transcription of the RPS5 gene is impaired, mostly due to a
      defect in transcriptional activation rather than to a defect in core promoter
      recognition, although the latter is slightly affected as well. Surprisingly, the
      RPS5 core promoter can be activated by various activation domains fused to a GAL4
      DNA binding domain, but not by the original upstream activating sequence (UAS) of
      the RPS5 gene. In addition, a heterologous CYC1 core promoter can be activated by
      RPS5-UAS at normal levels even in these mutants. These observations indicate that
      a distinct combination of core promoters and activators may exploit alternative
      activation pathways that vary in their requirement for TAF145 function. In
      addition, a particular function of TAF145 that is deleted in our mutants appears
      to be involved in both core promoter recognition and transcriptional activation.

PMID- 11337504
TI  - Identification of active site residues in glucosylceramide synthase. A nucleotide
      binding catalytic motif conserved with processive beta-glycosyltransferases.
AB  - Glucosylceramide synthase (GCS) transfers glucose from UDP-Glc to ceramide,
      catalyzing the first glycosylation step in the formation of higher order
      glycosphingolipids. The amino acid sequence of GCS was reported to be dissimilar
      from other proteins, with no identifiable functional domains. We previously
      identified His-193 of rat GCS as an important residue in UDP-Glc and GCS
      inhibitor binding; however, little else is known about the GCS active site. Here,
      we identify key residues of the GCS active site by performing biochemical and
      site-directed mutagenesis studies of rat GCS expressed in bacteria. First, we
      found that Cys-207 was the primary residue involved in GCS N-ethylmaleimide
      sensitivity. Next, we showed by multiple alignment that the region of GCS
      flanking His-193 and Cys-207 (amino acids 89-278) contains a D1,D2,D3,(Q/R)XXRW
      motif found in the putative active site of processive beta-glycosyltransferases
      (e.g. cellulose, chitin, and hyaluronan synthases). Site-directed mutagenesis
      studies demonstrated that most of the highly conserved residues were essential
      for GCS activity. We also note that GCS and processive beta-glycosyltransferases
      are topologically similar, possessing cytosolic active sites, with putative
      transmembrane domains immediately N-terminal to the conserved domain. These
      results provide the first extensive information on the GCS active site and show
      that GCS and processive beta-glycosyltransferases possess a conserved substrate
      binding/catalytic domain.

PMID- 11337505
TI  - Nuclear export of human beta-catenin can occur independent of CRM1 and the
      adenomatous polyposis coli tumor suppressor.
AB  - beta-Catenin is a mediator of the Wnt-signaling pathway. In many cancers, beta
      catenin is stabilized and accumulates in the nucleus where it associates with
      lymphoid-enhancing factor 1/ T-cell transcription factors to activate genes
      involved in cell transformation. Previously, we showed that adenomatous polyposis
      coli (APC) protein can regulate beta-catenin localization by nuclear export. In
      this study, we used in vitro transport assays to test whether cellular beta
      catenin can exit the nucleus independent of APC and the CRM1 export receptor. In
      digitonin-permeabilized SW480 (APC(mut/mut)) tumor cells, nuclear beta-catenin
      decreased >60% in export reactions in the absence of exogenous factors. Under
      similar conditions, nuclear c-ABL was only exported after the addition of
      cytosolic extract, and the export was blocked by the CRM1-specific inhibitor,
      leptomycin B. The nuclear export of beta-catenin was not blocked by leptomycin B
      treatment, revealing a CRM1- and APC-independent pathway. The export of beta
      catenin was sensitive to lower temperatures and the removal of ATP, indicating an
      active process. Ectopically expressed yellow fluorescent protein-beta-catenin
      also displayed CRM1-independent export. Conversely, the overexpression of the
      CRM1 transporter moderately stimulated export of nuclear beta-catenin, confirming
      that beta-catenin exits the nucleus by at least two distinct pathways. The
      shuttling ability of tumor cell beta-catenin has implications for its regulation
      and its role in transferring signals between the nucleus and plasma membrane.

PMID- 11337506
TI  - Activation of NF-kappa B via the Ikappa B kinase complex is both essential and
      sufficient for proinflammatory gene expression in primary endothelial cells.
AB  - Activation of the transcription factor NF-kappaB is necessary for full expression
      of tumor necrosis factor alpha (TNF-alpha)-inducible endothelial chemokines and
      adhesion molecules. However, a detailed analysis regarding contribution of the
      different NF-kappaB upstream components to endothelial activation has not been
      performed yet. We employed a retroviral infection approach to stably express
      transdominant (TD) mutants of IkappaBalpha, IkappaBbeta, or IkappaBepsilon and
      dominant negative (dn) versions of IkappaB kinases (IKK) 1 or 2 as well as a
      constitutively active version of IKK2 in human endothelial cells. TD
      IkappaBalpha, IkappaBbeta, and IkappaBepsilon were not degraded upon TNF-alpha
      exposure, and each prevented NF-kappaB activation. These TD IkappaB mutants
      almost completely inhibited the induction of monocyte chemoattractant protein-1,
      interleukin-8, intercellular adhesion molecule-1, vascular cell adhesion molecule
      1, and E-selectin expression by TNF-alpha, whereas interferon-gamma-mediated up
      regulation of intercellular adhesion molecule-1 and HLA-DR was not affected.
      Expression of dn IKK2 completely blocked TNF-alpha-induced up-regulation, whereas
      dn IKK1 showed a partial inhibition of expression of these molecules.
      Importantly, expression of constitutively active IKK2 was sufficient to drive
      full expression of all chemokines and adhesion molecules in the absence of
      cytokine. We conclude that the IKK/IkappaB/NF-kappaB pathway is crucial and
      sufficient for proinflammatory activation of endothelium.

PMID- 11337507
TI  - Regulation of the human MAT2B gene encoding the regulatory beta subunit of
      methionine adenosyltransferase, MAT II.
AB  - Methionine adenosyltransferase (MAT) catalyzes the biosynthesis of S
      adenosylmethionine (AdoMet), a key molecule in transmethylation reactions and
      polyamine biosynthesis. The MAT II isozyme consists of a catalytic alpha2 and a
      regulatory beta subunit. Down-regulation of the MAT II beta subunit expression
      causes a 6-10-fold increase in intracellular AdoMet levels. To understand the
      mechanism by which the beta subunit expression is regulated, we cloned the MAT2B
      gene, determined its organization, characterized its 5'-flanking sequences, and
      elucidated the in vitro and in vivo regulation of its promoter. Transcription of
      the MAT2B gene initiates at position -203 relative to the translation start site.
      Promoter deletion analysis defined a minimal promoter between positions +52 and
      +93 base pairs, a GC-rich region. Inclusion of the sequences between -4 and +52
      enhanced promoter activity; this was primarily because of an Sp1 recognition site
      at +9/+15. The inclusion of sequences up to position -115 provided full activity;
      this was attributed to a TATA at -32. The Sp1 site at position +9 was key for the
      formation of protein.DNA complexes. Mutation of both the Sp1 site at +9 and the
      TATA at -32 reduced promoter activity to its minimal level. Supershift assays
      showed no effect of the anti-Sp1 antibody on complex formation, whereas the anti
      Sp3 antibody had a strong effect on protein.DNA complex formation, suggesting
      that Sp3 is one of the main factors binding to this Sp1 site. Chromatin
      immunoprecipitation assays supported the involvement of both Sp1 and Sp3 in
      complexes formed on the MAT2B promoter. The data show that the 5'-untranslated
      sequences play an important role in regulating the MAT2B gene and identifies the
      Sp1 site at +9 as a potential target for modulating MAT2B expression, a process
      that can have a major effect on intracellular AdoMet levels.

PMID- 11337508
TI  - Sodium butyrate induces transcription from the G alpha(i2) gene promoter through
      multiple Sp1 sites in the promoter and by activating the MEK-ERK signal
      transduction pathway.
AB  - Sodium butyrate, an erythroid differentiation inducer and a histone deacetylase
      inhibitor, increases G alpha(i2) levels in differentiating K562 cells. Here we
      show that sodium butyrate induces G alpha(i2) gene transcription via sequences at
      -50/-36 and -92/-85 in the G alpha(i2) gene promoter. Both sequences contain core
      sequence motif for Sp1 binding; electrophoretic mobility shift as well as
      supershift assays confirmed binding to Sp1. Transcription from the G alpha(i2)
      gene promoter was also activated by two other histone deacetylase inhibitors,
      trichostatin A and Helminthsporium carbonium toxin (HC toxin), which also induce
      erythroblastic differentiation in K562 cells. However, hydroxyurea, a potent
      erythroid differentiation inducer in these cells, did not activate transcription
      from this gene promoter, indicating that promoter activation is inducer-specific.
      Mutations within the Sp1 sites at -50/-36 and -92/-85 in the G alpha(i2) gene
      promoter substantially decreased transcriptional activation by sodium butyrate,
      trichostatin A, or HC toxin. Transfection with constitutively activated ERKs
      indicated that this promoter can be activated through the MEK-ERK signal
      transduction pathway. Inhibition of the MEK-ERK pathway with U0126 or reduction
      in the expression of endogenous ERK with an antisense oligonucleotide to ERK
      significantly inhibited sodium butyrate- and HC toxin-induced transcription but
      had no effect on trichostatin A-induced transcription. Inhibition of the JNK and
      p38 MAPKs, using selective inhibitors, had no effect on sodium butyrate-induced
      transcription. In cells in which sodium butyrate induction of promoter activation
      had been inhibited by various concentrations of U0126, constitutively activated
      ERK2 reversed this inhibition. These results show that the MEK-ERK signal
      transduction pathway is important in butyrate signaling, which eventually
      converges in the cell nucleus.

PMID- 11337509
TI  - Identification of novel pheromone-response regulators through systematic
      overexpression of 120 protein kinases in yeast.
AB  - Protein kinases are well known to transmit and regulate signaling pathways. To
      identify additional regulators of the pheromone signaling apparatus in yeast, we
      evaluated an array of 120 likely protein kinases encoded by the yeast genome.
      Each kinase was fused to glutathione S-transferase, overexpressed, and tested for
      changes in pheromone responsiveness in vivo. As expected, several known
      components of the pathway (YCK1, STE7, STE11, FUS3, and KSS1) impaired the growth
      arrest response. Seven other kinases also interfered with pheromone-induced
      growth arrest; in rank order they are as follows: YKL116c (renamed PRR1) =
      YDL214c (renamed PRR2) > YJL141c (YAK1, SRA1) > YNR047w = YCR091w (KIN82) =
      YIL095w (PRK1) > YCL024w (KCC4). Inhibition of pheromone signaling by PRR1, but
      not PRR2, required the glutathione S-transferase moiety. Both kinases inhibited
      gene transcription after stimulation with pheromone, a constitutively active
      kinase mutant STE11-4, or overexpression of the transcription factor STE12.
      Neither protein altered the ability of the mitogen-activated protein kinase
      (MAPK) Fus3 to feedback phosphorylate a known substrate, the MAPK kinase Ste7.
      These results reveal two new components of the pheromone-signaling cascade in
      yeast, each acting at a point downstream of the MAPK.

PMID- 11337510
TI  - Stoichiometry of complexes between mannose-binding protein and its associated
      serine proteases. Defining functional units for complement activation.
AB  - Serum mannose-binding protein (MBP) initiates the lectin branch of the complement
      cascade by binding to sugars on the surfaces of microorganisms and activating two
      MBP-associated serine proteases (MASP-1 and MASP-2). Rat serum MBP consists of
      oligomers containing up to four copies of a subunit that is composed of three
      identical polypeptide chains. Biophysical analysis of intact and truncated MASPs
      indicates that each MASP is a homodimer that is stabilized through interactions
      involving an N-terminal CUB domain. The binding sites for MBP are formed from the
      three N-terminal MASP domains, in which two CUB modules interact with MBP. Each
      MASP dimer contains binding sites for two MBP subunits. Both sites must be
      occupied by subunits from a single MBP oligomer to form a stable complex. Thus,
      the smallest functional unit for complement activation consists of MBP dimers
      bound to MASP-1 or MASP-2 homodimers. Trimers and tetramers of MBP form complexes
      containing up to two MASPs. The results reveal how MASP-1 and MASP-2 can function
      independently to activate the complement cascade.

PMID- 11337511
TI  - A role for Sp1 in the transcriptional regulation of hepatic triacylglycerol
      hydrolase in the mouse.
AB  - Microsomal triacylglycerol hydrolase (TGH) hydrolyzes stored triacylglycerol in
      cultured hepatoma cells (Lehner, R., and Vance, D. E. (1999) Biochem. J. 343, 1
      10). We studied expression of TGH in murine liver and found both protein and mRNA
      increased dramatically at 27 days after birth. Nuclear run-on assays demonstrated
      that this was due to increased transcription. We cloned 542 base pairs upstream
      of the transcriptional start site of the murine TGH gene. Electrophoretic
      mobility shift assays demonstrated enhanced binding of hepatic nuclear proteins
      from 27-day-old mice to the murine TGH promoter, yielding three differentially
      migrating complexes. DNase I footprint analysis localized these complexes to two
      distinct regions: site A contains a putative Sp binding site, and site B contains
      a degenerate E box. We transfected primary murine hepatocytes with a series of 5'
      deletion constructs upstream of the reporter luciferase cDNA. Positive control
      elements were identified in a segment containing site A. Competitive
      electrophoretic mobility shift assays and supershift assays demonstrated that
      site A binds Sp1 and Sp3. Transcriptional activation assays in Schneider SL-2
      insect cells demonstrated that Sp1 is a potent activator of the TGH promoter.
      These experiments directly link increased TGH expression at the time of weaning
      to transcriptional regulation by Sp1.

PMID- 11337512
TI  - Phosphorylated Ca2+-ATPase stable enough for structural studies.
AB  - The atomic structure of sarcoplasmic reticulum Ca(2+)-ATPase, in a Ca(2+)-bound
      conformation, has recently been elucidated (Toyoshima, C., Nakasako, M., Nomura,
      H. & Ogawa, H. (2000) Nature 405, 647-655). Important steps for further
      understanding the mechanism of ion pumps will be the atomic structural
      characterization of different key conformational intermediates of the transport
      cycle, including phosphorylated intermediates. Following our previous report
      (Champeil, P., Henao, F., Lacapere, J.-J. & McIntosh, D. B. (2000) J. Biol. Chem.
      276, 5795-5803), we show here that it is possible to prepare a phosphorylated
      form of sarcoplasmic reticulum Ca(2+)-ATPase (labeled with fluorescein
      isothiocyanate) with a week-long stability both in membranes and in mixed lipid
      detergent micelles. We show that this phosphorylated fluorescein isothiocyanate
      ATPase can form two-dimensional arrays in membranes, similar to those that were
      used previously to reconstruct from cryoelectron microscopy images the three
      dimensional structure of Ca(2+)-free unphosphorylated ATPase. The results also
      provide hope that crystals of phosphorylated Ca(2+)-ATPase suitable for x-ray
      crystallography will be achieved.

PMID- 11337513
TI  - Technegas versus (81m)Kr ventilation-perfusion scintigraphy: a comparative study
      in patients with suspected acute pulmonary embolism.
AB  - 81mKr is widely used as a ventilation agent to diagnose pulmonary embolism (PE).
      However, (81m)Kr is expensive, which limits its continuous availability.
      Technegas can be an alternative ventilation agent with the advantage of being
      less expensive and available daily. The aim of this study was to compare the
      value of technegas with that of (81m)Kr in the detection of PE. METHODS: Ninety
      two consecutive patients (29 men; mean +/- SD, 53 +/- 17 y old) with at least one
      segmental perfusion defect (Hull criteria) were studied prospectively. Perfusion
      and ventilation (V/Q) lung scintigraphy with both technegas and (81m)Kr were
      performed within 24 h on all patients. V/Q lung scan results were classified as
      high probability for PE (normal ventilation study) or nondiagnostic (abnormal
      ventilation study). All V/Q lung scans were read by two experienced nuclear
      physicians in consensus. For the intra- and interobserver variabilities, two
      experienced observers independently read the V/Q lung scans. RESULTS: (81m)Kr and
      technegas showed a good agreement (kappa, 0.68; 95% confidence interval [CI],
      0.53-0.82). However, technegas significantly increased the number of
      nondiagnostic V/Q lung scans (P: = 0.035). In 15 patients, a discrepancy was
      found between (81m)Kr and technegas. False-positive V/Q lung scan results
      occurred in 4 of 12 patients (33%) with (81m)Kr and in 2 of 3 patients (66%) with
      technegas. The intra- and interobserver variabilities were 0.71-0.88 (95% CI,
      0.56-1.0) for perfusion/(81m)Kr and 0.74-0.96 (95% CI, 0.58-1.0) for
      perfusion/technegas. CONCLUSION: In comparison with (81m)Kr, technegas does not
      result in more false-positive V/Q lung scan results. The use of technegas,
      however, increases the number of nondiagnostic V/Q lung scan results, which would
      increase the demand for further additional testing to confirm or refute PE.

PMID- 11337514
TI  - Automatic determination of left ventricular ejection fraction from gated blood
      pool tomography.
AB  - The aim of this study was to develop and validate a new algorithm to
      automatically compute left ventricular ejection fraction (LVEF) from gated blood
      pool tomography (GBPT). The results were compared with those of conventional
      planar radionuclide angiocardiography (PRNA). METHODS: Fifty-three consecutive
      patients received an injection of 740 MBq (99m)Tc-labeled human serum albumin.
      PRNA and GBPT were performed consecutively in a random sequence. PRNA served as
      the reference, and GBPT images were processed using a new edge detection
      algorithm. The algorithm is fast (<45 s), fully automatic, and works in three
      dimensional space. The method includes identification of the valve plane and the
      septum. The left ventricular cavity at end-diastole is delineated by segmentation
      using an iterative threshold technique. An optimal threshold is reached when the
      corresponding isocontour best fits the first derivative of the end-diastolic
      count distribution in three dimensions. This optimal threshold is then applied to
      delineate the left ventricular cavity on the other time bins. The data are
      corrected for the partial-volume effect. Left ventricular volumes are determined
      using a geometry-based method and are used to calculate the ejection fraction.
      RESULTS: The success rate of the new algorithm was 94%. LVEFs calculated from
      GBPT agreed well with those calculated from PRNA (r = 0.78; GBPT = 0.94 PRNA +
      6.33). The systematic error was 2.8%, and the random error was 8.8%. Excellent
      inter- and intraobserver reproducibility was found, with average differences of
      1.1% +/- 4.6% and 1.1% +/- 5.0%, respectively, between the two measurements.
      CONCLUSION: This new algorithm provides a fast, automated, and objective method
      to calculate LVEF from GBPT.

PMID- 11337515
TI  - Differential diagnosis of Parkinson's disease and vascular parkinsonism by
      (99m)Tc-TRODAT-1.
AB  - The aim of this study was to use brain SPECT to differentiate vascular
      parkinsonism (VP) from Parkinson's disease. METHODS: Fourteen VP patients (age
      range, 59-87 y; mean age, 70 +/- 7.5 y), 30 Parkinson's disease patients (age
      range, 54-84 y; mean age, 65 +/- 8.8 y), and 26 healthy (control) individuals
      (age range, 50-85 y; mean age, 60 +/- 9 y) were examined. A 925-MBq (25 mCi) dose
      of (99m)Tc-TRODAT-1 was injected intravenously, and brain SPECT images were
      acquired 4 h after injection. The ratio of specific to nonspecific striatal
      (99m)Tc-TRODAT-1 binding was measured and compared. RESULTS: After a region-of
      interest analysis of the images from VP patients, Parkinson's disease patients,
      and healthy volunteers was performed to obtain ratios of putamen to occipital and
      striatal to occipital binding as a measurement of specific binding to the
      dopamine transporters in these regions of the brain, where dopamine neurons are
      concentrated, the specific binding in the 14 VP patients was slightly lower than
      but not statistically different from that of the healthy individuals in both
      putamen and caudate areas. A significant decrease in uptake of (99m)Tc-TRODAT-1
      in the striatum (P<0.01) was found in Parkinson's disease patients. Reduction of
      the uptake was more pronounced in the contralateral putamen of Parkinson's
      disease patients than that of VP patients (P<0.001). A significant bilateral
      striatal asymmetry was also observed in Parkinson's disease patients but not in
      VP patients (P< 0.01). CONCLUSION: Our findings clearly show that, for VP
      patients, (99m)Tc-TRODAT-1 SPECT is a reliable method to differentiate VP from
      Parkinson's disease. Further studies, including those to differentiate
      Parkinson's disease from arteriosclerotic parkinsonism and patients with both VP
      and Parkinson's disease, are needed to help rule out the possibility of
      Parkinson's disease as early as possible.

PMID- 11337516
TI  - Comparison of (18)F-FDG, (131)I-Na, and (201)Tl in diagnosis of recurrent or
      metastatic thyroid carcinoma.
AB  - There are several reports about the usefulness of (18)F-FDG PET in thyroid
      cancer. However, few studies have compared FDG PET with (131)I and (201)Tl
      scintigraphy. The aim of this study was to evaluate the clinical significance of
      whole-body FDG PET in differentiated thyroid cancer and to compare the results
      with those obtained from (131)I and (201)Tl scintigraphy. METHODS: Whole-body FDG
      PET was performed on 32 patients (10 men, 22 women; age range, 30-77 y; mean age,
      54 y) with differentiated thyroid cancer (5 cases of follicular cancer and 27 of
      papillary cancer) after total thyroidectomy. An overall clinical evaluation was
      performed, including cytology, thyroglobulin level, sonography, MRI, and CT, to
      allow a comparison with functional imaging results for each patient. Metastatic
      regions were divided into five areas: neck, lung, mediastinum, bone, and other.
      Multiple lesions in one area were defined as one lesion. The tumor-to-background
      ratio (TBR) was measured for the lesions that were positive for both (201)Tl
      uptake and FDG PET uptake. RESULTS: The number of lesions totaled 47. Forty-one
      (87%) were detected by all scintigraphic methods. FDG uptake was concordant with
      (131)I uptake in only 18 lesions (38%). FDG uptake was concordant with (201)Tl
      uptake in 44 lesions (94%). Only one lesion was negative for FDG uptake and
      positive for (201)Tl uptake, and two lesions were positive for FDG uptake and
      negative for (201)Tl uptake. A significant correlation was seen between the TBR
      of (201)Tl and that of FDG (r = 0.69; P<0.05). CONCLUSION: These data indicate
      that for detecting metastatic lesions, FDG PET and (131)I scintigraphy may
      provide complementary information, whereas FDG PET may provide results similar to
      those of (201)Tl scintigraphy. Thus, the combination of (131)I scintigraphy and
      FDG PET (or (201)Tl scintigraphy) is the method of choice for detecting
      metastatic thyroid cancer after total thyroidectomy.

PMID- 11337517
TI  - Lymphoscintigraphy and sentinel node localization in breast cancer patients: a
      comparison between 1-day and 2-day protocols.
AB  - The purpose of this study was to compare the results of isotope injection the
      morning of surgery (1-d protocol) with isotope injection the day before surgery
      (2-d protocol) in patients having sentinel lymph node (SLN) biopsy for breast
      cancer. METHODS: The 1-d (protocol 1) and 2-d (protocol 2) protocols included 514
      and 152 patients, respectively, treated contemporaneously by surgeons experienced
      with the SLN biopsy technique. All had preoperative lymphoscintigraphy (LSG) and
      SLN biopsy using both blue dye and (99m)Tc-sulfur colloid. All patients had a
      single-site intradermal injection of unfiltered (99m)Tc-sulfur colloid in 0.05 mL
      normal saline: 3.7 MBq (0.1 mCi) on the morning of surgery for protocol 1 and
      18.5 MBq (0.5 mCi) on the afternoon before surgery for protocol 2. RESULTS: The
      patients in protocols 1 and 2 were comparable in terms of age, tumor size, tumor
      location, histologic type, node positivity, and frequency of a previous surgical
      biopsy. Comparing protocols 1 and 2, early (30 min) LSG images found the SLN
      equally often (69% vs. 68%). Isotope identified the SLN equally often at surgery
      (93% vs. 97%) as did isotope plus dye (98% vs. 99%). A comparable number of SLNs
      was found (2.5 vs. 2.8 per axilla), and the concordance between isotope and dye
      in the SLN was also comparable (97% vs. 95%). Late LSG images (at 2 h, possible
      only for protocol 2) identified the SLN in significantly more patients compared
      with early images (86% vs. 68%). CONCLUSION: With unfiltered (99m)Tc-sulfur
      colloid injected intradermally, the results of SLN biopsy under the 1-d and 2-d
      protocols are virtually identical. A 2-d protocol allows increased efficiency in
      scheduling, both for nuclear medicine physicians and for the operating room, with
      no compromise in the effectiveness of SLN mapping.

PMID- 11337518
TI  - Reproducibility of lymphoscintigraphy in cutaneous melanoma: can we accurately
      detect the sentinel lymph node by expanding the tracer injection distance from
      the tumor site?
AB  - The aim of the study was to determine whether the sentinel lymph node (SLN) can
      be accurately detected in cutaneous melanoma patients when the injection distance
      from the tumor site is expanded. METHODS: In 100 patients with cutaneous
      melanoma, lymphoscintigraphy was performed twice. First, we injected 37 MBq
      (99m)Tc nanocolloid intracutaneously at a 2- to 5-mm distance from either the
      melanoma or the biopsy scar. The injection was followed by dynamic imaging, which
      continued until the SLN became visible. On another day, we repeated the
      investigation, injecting the radiopharmaceutical intracutaneously exactly 10 mm
      from the previous injection site. The detected SLNs of both investigations were
      compared to determine the number and location of SLNs for each patient. RESULTS:
      The SLN identification rate was 94% with close injection and 100% with 10-mm
      distant injection. All SLNs detected with close injection were visible with
      distant injection. In 84 of 100 patients, the images of both investigations
      showed the same number and location of SLNs. In the remaining 16 patients, an
      additional SLN was detected with the distant injection. CONCLUSION: The
      reproducibility of lymphoscintigraphy using different injection distances was
      84%. The discordance in the remaining 16% was caused by detection of a lymph node
      in addition to the original SLN with distant injection. Diagnostic excision of
      the primary tumor before lymphoscintigraphy was possible without preventing
      detection of the original SLN. However, in 16% of our patients, excision of an
      additional lymph node had to be considered when lymphoscintigraphy was performed
      after diagnostic excision.

PMID- 11337519
TI  - Reproducibility of cutaneous lymphoscintigraphy: same or different lymphatic
      routes and sentinel nodes after reinjection?

PMID- 11337520
TI  - Radiolabeled amino acids: basic aspects and clinical applications in oncology.
AB  - As the applications of metabolic imaging are expanding, radiolabeled amino acids
      may gain increased clinical interest. This review first describes the basic
      aspects of amino acid metabolism, then continues with basic aspects of
      radiolabeled amino acids, and finally describes clinical applications, with an
      emphasis on diagnostic value. A special focus is on (11)C-methionine, (11)C
      tyrosine, and (123)I-iodomethyltyrosine, because these have been most used
      clinically, although their common affinity for the L-transport systems may limit
      generalization to other classes of amino acids. The theoretic and preclinical
      background of amino acid imaging is sound and supports clinical applications. The
      fact that amino acid imaging is less influenced by inflammation may be
      advantageous in comparison with (18)F-FDG PET imaging, although tumor specificity
      is not absolute. In brain tumor imaging, the use of radiolabeled amino acids is
      established, the diagnostic accuracy of amino acid imaging seems adequate, and
      the diagnostic value seems advantageous. The general feasibility of amino acid
      imaging in other tumor types has sufficiently been shown, but more research is
      required in larger patient series and in well-defined clinical settings.

PMID- 11337521
TI  - Use of (99m)Tc-labeled liposomes encapsulating blue dye for identification of the
      sentinel lymph node.
AB  - Colloidal radiopharmaceuticals are commonly used in combination with blue dye for
      localization of the sentinel node. Liposomes are colloidal particles composed of
      spontaneously forming lipid spheres that can carry a wide variety of diagnostic
      and therapeutic agents. Conventional liposomes are poorly retained in lymph nodes
      (<2% of the subcutaneously injected dose). We have previously described a system
      for increasing the retention of liposomes in the lymph nodes by approximately 7
      fold. This system is comprised of subcutaneously injected biotin-coated
      liposomes, followed by an adjacent injection of avidin. When the avidin moves
      into the lymphatic vessels, it causes aggregation of the biotin-coated liposomes
      that are also in the process of migrating through the lymphatic vessels. These
      aggregated liposomes become entrapped in the next encountered lymph node. In this
      study, we use this novel lymph node delivery system with liposomes that
      encapsulate blue dye, resulting in intense blue staining of the sentinel node.
      These liposomes can also be labeled with (99m)Tc, permitting scintigraphic
      imaging and radioguided probe localization of the sentinel node. METHODS:
      Liposomes coated with biotin and coencapsulating blue dye and glutathione were
      labeled with (99m)Tc using hexamethylpropyleneamine oxime. Rabbits were
      subcutaneously administered 0.3 mL (99m)Tc-biotin-liposomes containing blue dye
      in both hind feet, followed by a subcutaneous injection (0.3 mL) of 5 mg avidin
      in only one hind foot (experimental). The other hind foot served as a control.
      RESULTS: Labeling efficiencies (mean +/- SEM) for liposomes encapsulating blue
      dye were 92.1% +/- 1.9%. Necropsy at 24 h revealed that the popliteal node on the
      experimental leg receiving the avidin was intensely blue stained compared with
      virtually no blue coloration of the control node. Tissue counts of these nodes
      were 12.2 +/- 1.5 percentage injected dose (%ID) in the experimental node
      compared with 1.2 +/- 0.1 %ID in the control nodes (P<0.0001). CONCLUSION: Biotin
      liposomes encapsulating blue dye can be successfully labeled with (99m)Tc,
      providing a convenient option for the visualization and radiolocalization of the
      sentinel node. This biotin-liposome/avidin system may also have potential for the
      delivery of therapeutic drugs and radiopharmaceuticals to lymph nodes.

PMID- 11337522
TI  - Let every node count!

PMID- 11337523
TI  - Overestimation of the LVEF by quantitative gated SPECT in simulated left
      ventricles.
AB  - During routine myocardial perfusion imaging, a common observation is that
      patients with normal cardiac function and small hearts, in particular small
      women, have higher left ventricular ejection fractions (LVEFs), as measured by
      quantitative gated SPECT (QGS) software, than anticipated, often markedly so. The
      goal of this project was to determine if the QGS LVEF varies with the change in
      end-diastolic left ventricular volume (EDV) and in particular to verify that the
      clinically observed phenomenon of falsely elevated QGS LVEF in patients with
      small hearts is actually occurring. METHODS: A series of mathematically defined
      left ventricles (LVs) was produced by varying the EDV and targeted LVEF (tLVEF).
      These were created using concentric hemiellipsoids with nine different EDVs. The
      tLVEF was varied from 15% to 75% by 5% increments for a total of 13 different
      ejection fractions. These datasets were then smoothed, creating a total of 234
      sets. The smoothed and unsmoothed images were then processed using QGS software.
      The LVEFs and EDVs were recorded. RESULTS: For lower LVEFs the agreement between
      the QGS LVEF and the tLVEF is good. A marked overestimation occurs when the EDVs
      are low and the ejection fractions are in the higher range. This effect is
      greater in the smoothed images. CONCLUSION: An artifactual increase in the LVEF
      can occur when measurements are made with the QGS software. These data argue
      against using QGS LVEF for monitoring the LVEF in patients with small hearts. Our
      data imply that a mildly decreased LVEF may still appear to be in the normal
      range when measured by QGS software.

PMID- 11337524
TI  - Particle size analysis of (99m)Tc-labeled and unlabeled antimony trisulfide and
      rhenium sulfide colloids intended for lymphoscintigraphic application.
AB  - Colloidal particle size is an important characteristic to consider when choosing
      a radiopharmaceutical for mapping sentinel nodes in lymphoscintigraphy. METHODS:
      Photon correlation spectroscopy (PCS) and transmission electron microscopy (TEM)
      were used to determine the particle size of antimony trisulfide and rhenium
      sulfide colloids, and membrane filtration (MF) was used to determine the
      radioactive particle size distribution of the corresponding (99m)Tc-labeled
      colloids. RESULTS: Antimony trisulfide was found to have a diameter of 9.3 +/-
      3.6 nm by TEM and 18.7 +/- 0.2 nm by PCS. Rhenium sulfide colloid was found to
      exist as an essentially trimodal sample with a d(v(max1)) of 40.3 nm, a
      d(v(max2)) of 438.6 nm, and a d(v) of 650-2200 nm, where d(v) is volume diameter.
      (99m)Tc-antimony trisulfide by MF showed that more than 96% of radioactive
      particles were smaller than 100 nm; however, (99m)Tc-rhenium sulfide showed that
      more than 21% were smaller than 100 nm. These radioactive colloids were used with
      seven different membrane compositions and found not to adsorb significantly to
      any of them. CONCLUSION: MF was validated as a simple and reliable technique to
      estimate the percentage radioactive particle size distribution.

PMID- 11337525
TI  - Quantitative kinetics of [124I]FIAU in cat and man.
AB  - For the assessment of the efficacy of clinical gene therapy trials, different
      imaging modalities have been developed that enable a noninvasive assessment of
      location, magnitude, and duration of transduced gene expression in vivo. These
      imaging methods rely on a combination of an appropriate marker gene and a
      radiolabeled or paramagnetic marker substrate that can be detected by PET or MRI.
      Here, we assess whether the nucleoside analog 2'-fluoro-2'-deoxy-1beta-D
      arabinofuranosyl-5-iodouracil (FIAU), a specific marker substrate for herpes
      simplex virus type 1 thymidine kinase (HSV-1-tk) gene expression, penetrates the
      blood-brain barrier (BBB) as an essential prerequisite for a noninvasive
      assessment of HSV-1-tk gene expression in gliomas. METHODS: No-carrier-added
      [(124)I]FIAU was synthesized by reacting the precursor 2'-fluoro-2'-deoxy-1beta-D
      arabinofuranosyluracil (FAU) with carrier-free [(124)I]NaI. The course of
      biodistribution of [(124)I]FIAU was investigated in anesthetized cats (n = 3;
      organs) and in one patient with a recurrent glioblastoma (plasma and brain) by
      PET imaging over several hours (cats, 1-22 h) to several days (patient, 1-68 h).
      FIAU PET was performed in conjunction with multitracer PET imaging (cerebral
      blood flow and cerebral metabolic rate of O(2) in cats only; cerebral metabolic
      rate of glucose and [(11)C]methionine in all subjects). A region-of-interest
      analysis was performed on the basis of coregistered high-resolution MR images.
      The average radioactivity concentration was determined, decay corrected, and
      recalculated as percentage injected dose per gram of tissue (%ID/g) or as
      standardized uptake values (SUVs). RESULTS: The average chemical yield of
      [(124)I]FIAU synthesis was 54.6% +/- 6.8%. The chemical and radiochemical
      purities of [(124)I]FIAU were found to be >98% and >95%, respectively. In cats,
      the kinetic analysis of [(124)I]FIAU-derived radioactivity showed an early peak
      (1-2 min after injection) in heart and kidneys (0.20 %ID/g; SUV, 4.0) followed by
      a second peak (10-20 min after injection) in liver and spleen (0.16 %ID/g; SUV,
      3.2) with subsequent clearance from tissues and a late peak in the bladder (10-15
      h after injection). In the unlesioned cat brain, no substantial [(124)I]FIAU
      uptake occurred throughout the measurement (<0.02 %ID/g; SUV, <0.4). In the
      patient, [(124)I]FIAU uptake in normal brain was also very low (<0.0002 %ID/g;
      SUV, <0.16). In contrast, the recurrent glioblastoma revealed relatively high
      levels of [(124)I]FIAU-derived radioactivity (5-10 min after injection; 0.001
      %ID/g; SUV, 0.8), which cleared slowly over the 68-h imaging period. CONCLUSION:
      The PET marker substrate FIAU does not penetrate the intact BBB significantly
      and, hence, is not the marker substrate of choice for the noninvasive
      localization of HSV-1-tk gene expression in the central nervous system under
      conditions in which the BBB is likely to be intact. However, substantial levels
      of [(124)I]FIAU-derived radioactivity may occur within areas of BBB disruption
      (e.g., glioblastoma), which is an essential prerequisite for imaging clinically
      relevant levels of HSV-1-tk gene expression in brain tumors after gene therapy by
      FIAU PET. For this purpose, washout of nonspecific radioactivity should be
      allowed for several days.

PMID- 11337526
TI  - In vivo detection of intervertebral disk injury using a radiolabeled monoclonal
      antibody against keratan sulfate.
AB  - In the intervertebral disk, proteoglycans form the major part of the
      extracellular matrix, surrounding chondrocytelike disk cells. Keratan sulfate is
      a major constituent of proteoglycans. METHODS: We have radioiodinated a
      monoclonal antibody raised against keratan sulfate. This antibody was injected
      into rats (n = 6), and the biodistribution was studied. A model of intervertebral
      disk injury was developed, and two tail disks in each animal with both acute (2
      wk old) and subacute (7 wk old) injuries were studied for in vivo antibody
      uptake. RESULTS: The biodistribution at 72 h was as follows: blood, 0.0018
      percentage injected dose per gram of tissue (%ID/g); lung, 0.0106 %ID/g;
      esophagus, 0.0078 %ID/g; kidney, 0.0063 %ID/g; liver, 0.0047 %ID/g; spleen,
      0.0046 %ID/g; heart, 0.0036 %ID/g; thyroid, 0.0034 %ID/g; muscle, 0.0017 %ID/g;
      and bone, 0.0016 %ID/g. In the subacute stage, a significant difference (P <
      0.006) was found in antibody uptake between injured disks (n = 12) and adjacent
      healthy disks (n = 12). In vivo gamma imaging showed increased uptake in other
      animals having lumbar disk injuries (2, 7, and 17 d after injury). Cartilage
      tissue, such as the trachea, was studied separately and showed extremely high
      antibody uptake, 0.10 %ID/g. Rat trachea was also visualized on gamma images.
      CONCLUSION: Our data suggest that antibodies against nucleus pulposus components,
      such as proteoglycans, can be used for in vivo detection of intervertebral disk
      injury. This finding is in spite of the minimal circulation present in
      intervertebral disks.

PMID- 11337528
TI  - Contribution to red marrow absorbed dose from total body activity: a correction
      to the MIRD method.
AB  - The contribution to red marrow absorbed dose from beta-emitting radionuclides
      distributed uniformly in the total body can be overestimated using either MIRD 11
      or MIRDOSE3. The S value assigned to the red marrow target region from activity
      distributed in the remainder of the body is of particular concern. The assumption
      that the specific absorbed fraction for total body irradiating red marrow and
      other skeletal tissues is the inverse of the total-body mass can result in an
      inappropriate remainder-of-body contribution to marrow dose. We evaluated
      differences in the calculation of marrow dose using MIRD 11 and MIRDOSE3
      formulations and developed methods to correct the results from either to remove
      inappropriate contributions. When bone takes up significantly less activity than
      is predicted from an apportionment of remainder-tissue activity based on mass,
      the standard remainder-of-body correction may substantially overestimate the
      electron component of the S value from remainder tissues to red marrow using
      either MIRD 11 or MIRDOSE3. If bone takes up activity, this contribution is
      negligible using MIRD 11 S values but remains with MIRDOSE3 S values. This
      overestimate can be significant, particularly when the residence time of activity
      in the remainder of the body is much higher than in the red marrow and a
      different correction is needed. As the ratio of the remainder of body to marrow
      residence time is lowered, the overestimate becomes less significant. CONCLUSION:
      In this article, we show the magnitude of this overestimate (which is most
      important for nuclides with large "nonpenetrating" emission components and for
      pharmaceuticals that have a large ratio of remainder of body to marrow residence
      times), show the appropriate corrections to be made in each case, and propose a
      new method for calculating marrow dose contributions that will avoid this
      complication in future applications. Because all models give approximate doses
      for real patients, with uncertainties within those involved in these corrections,
      we do not suggest that changes be made to existing marrow dose estimates. We
      suggest only that future calculations be as accurate as possible.

PMID- 11337527
TI  - Automated PET attenuation correction model for functional brain imaging.
AB  - The failure to compensate for subject motion between attenuation correction scans
      and emission scans precludes the optimization of functional brain imaging
      techniques. We have developed an automated method for attenuation correction that
      compensates for subject motion by deriving each set of correction factors from
      the corresponding emission study. METHODS: The technique consists of generation
      of an estimated skull image by filtered backprojection of the reciprocal of an
      emission sinogram; estimation of the thickness and radius of the skull on
      profiles extracted from the image; scaling the radius and thickness values to
      generate a model of the brain, skull, and scalp; and assignment of attenuation
      coefficients to the head model for generation of attenuation correction factors.
      Values for scale factors and tissue attenuation coefficients were determined
      empirically by fitting the emission-derived head model to measured transmission
      data in five subjects using nonlinear regression (group A). The average model
      parameters, across five datasets (group A), were then used to generate
      attenuation maps for five independent emission studies (group B). Mean-squared
      error values were calculated between the measured transmission data and the two
      model groups. For comparison, mean squared error values were calculated between
      the measured transmission data and homogeneous ellipses that were manually fitted
      to emission images. RESULTS: The difference between the mean squared error for
      groups A and B was not significant (P>0.8), indicating that model parameters from
      a small group can be used for other subjects without further fitting. The mean
      squared error for the automated method was significantly lower than that of the
      ellipse method (P<0.001). The method reduced emission image variance, resulting
      in a higher peak Z value in activation images. The elimination of measured
      transmission scans resulted in a reduction in scan time ( approximately 15 min)
      and radiation exposure ( approximately 0.5-1.6 mrem). CONCLUSION: We have
      developed an automated attenuation correction method that compensates for subject
      motion between scans, accurately reproduces the characteristics of the head, and
      eliminates the use of measured transmission data to reduce scan duration,
      statistical noise propagation, and radiation dose.

PMID- 11337529
TI  - An analytic dosimetry study for the use of radionuclide-liposome conjugates in
      internal radiotherapy.
AB  - A dosimetric analysis has been performed to evaluate the potential of liposome
      systems as carriers of radionuclides in internal radiotherapy. METHODS:
      Pharmacokinetic data for a variety of liposome constructs (multilamellar vesicles
      [MLV]; small unilamellar vesicles [SUV]; and sterically stabilized liposomes,
      monosialoganglioside [G(M1)]-coated) were used to obtain tumor and normal-organ
      absorbed dose estimates for (67)Cu, (188)Re, (90)Y, and (131)I. Dosimetry was
      performed for two tumor models: subcutaneous Ehrlich ascites tumor, growing
      intramuscularly, and C26 colon carcinoma, growing intrahepatically. Dose
      estimates were obtained using the MIRD schema. Tumor doses were obtained assuming
      local deposition of electron energy; photon contributions were incorporated
      assuming spheric tumor geometry. With the conservative assumption that
      intravenously administered liposomes achieve rapid equilibration with the red
      marrow extracellular fluid volume, red marrow absorbed dose estimates were
      obtained from blood kinetics. RESULTS: For intramuscular tumors, absorbed dose
      ratios for tumor to red marrow ranged from 0.93 ((131)I-MLV) to 13.9 ((90)Y-SUV).
      Tumor-to-liver ratios ranged from 0.08 ((188)Re-MLV) to 0.92 ((188)Re-SUV);
      corresponding values for tumor to spleen were 0.13 ((90)Y-MLV) and 0.54 ((188)Re
      G(M1)). The optimal combination of radionuclide and liposome system was obtained
      with (90)Y-SUV. Tumor-to-liver ratios for the G(M1)-coated construct were
      greatest when the tumor was intrahepatic (1.13 for (90)Y). For a given liposome
      system, absorbed dose ratios for tumor to normal tissue exhibited up to a twofold
      variation depending on the radionuclide selected. CONCLUSION: This study provides
      a dosimetric evaluation for the use of some liposome systems as carriers in
      targeted radionuclide therapy. Although much further work must be undertaken
      before any clinical application is considered, these results suggest that
      radionuclide targeting using liposomes is feasible and may have the advantage of
      reduced red marrow absorbed dose.

PMID- 11337530
TI  - Chemotaxis, viability, and labeling stability of leukocytes labeled with (99m)Tc
      exametazime stabilized with methylene blue.
AB  - The in vitro viability, chemotaxis, and labeling stability of leukocytes labeled
      using (99m)Tc-exametazime stabilized with methylene blue were evaluated and
      compared with those obtained using nonstabilized (99m)Tc-exametazime. METHODS:
      Two identical leukocyte populations, from 30 healthy donors, were labeled
      simultaneously using freshly prepared and 2-h-old stabilized (99m)Tc-exametazime.
      The following quality control techniques were performed on each labeled leukocyte
      sample: eosin Y staining, chemotaxis radioassay, and labeling stability at 2 h
      after labeling. RESULTS: Eosin Y staining showed a cell viability of at least 98%
      in all samples, without a significant statistical difference between the
      populations. Chemotactic indices obtained with leukocytes labeled with freshly
      prepared, unstabilized (99m)Tc-exametazime were statistically greater than those
      obtained using (99m)Tc-exametazime stabilized with methylene blue (z = 2.41;
      P<0.02). Labeling stability at 2 h after labeling was the same for both
      populations. CONCLUSION: The use of (99m)Tc-exametazime stabilized with methylene
      blue for leukocyte radiolabeling does not affect either cell membrane integrity
      or labeling stability but can cause a decrease in the cell chemotactic capacity
      that discourages its clinical use.

PMID- 11337531
TI  - Optimal quality (131)I-monoclonal antibodies on high-dose labeling in a large
      reaction volume and temporarily coating the antibody with IODO-GEN.
AB  - A novel, facile procedure for efficient coupling of high doses of (131)I to
      monoclonal antibodies (MAbs) was developed with minimal chemical and radiation
      damage. METHODS: To diminish the radiation and chemical burden during labeling,
      iodination was performed in a large reaction volume and by temporarily coating
      the MAb with a minimal amount of IODO-GEN. The MAb was coated by injection of
      IODO-GEN (dissolved in acetonitrile [MeCN]) into the aqueous MAb solution, and
      the coating was subsequently removed by addition of ascorbic acid. For
      chemoprotection before, during, and after PD-10 purification of the (131)I-MAbs,
      ascorbic acid and human serum albumin were used. The effects of autoradiolysis in
      the starting (131)I solution were countered by treatment with NaOH and ascorbic
      acid. For this so-called IODO-GEN-coated MAb method, the sensitive chimeric MAb
      MOv18 (c-MOv18) and the more robust murine MAbs K928 and E48 were used. The high
      dose (131)I-labeled MAbs were characterized for radiochemical purity and MAb
      integrity by thin-layer chromatography, high-performance liquid chromatography,
      and sodium dodecyl sulfate polyacrylamide gel electrophoresis followed by
      phosphor imager quantification. The high-dose (131)I-labeled MAbs were also
      characterized for immunoreactivity. The radiopharmacokinetics and biodistribution
      of (131)I-c-MOv18 were analyzed in human tumor-bearing nude mice. For comparison,
      (131)I-c-MOv18 batches were made using the conventional chloramine-T or IODO-GEN
      coated vial method. RESULTS: Conventional high-dose labeling of 5 mg c-MOv18 with
      4.4 GBq (131)I resulted in a labeling yield of 60%, a radiochemical purity of
      90%, an immunoreactive fraction of 25% (72% being the maximum in the assay used),
      and the presence of aggregation and degradation products. Using similar amounts
      of (131)I and MAb in the IODO-GEN-coated MAb method, 85%-89% overall
      radiochemical yield, at least 99.7% radiochemical purity, and full preservation
      of MAb integrity and immunoreactivity were achieved. For this labeling, 5 mg MAb
      were coated with 35 microg IODO-GEN during 3 min in a reaction volume of 6 mL.
      Also, biodistribution was optimal, and tumor accumulation was superior to that of
      coinjected (125)I-c-MOv18 labeled according to the conventional IODO-GEN-coated
      vial method. CONCLUSION: A new, facile, high-dose (131)I-labeling method was
      developed for production of (131)I-labeled MAbs with optimal quality for use in
      clinical radioimmunotherapy.

PMID- 11337532
TI  - MIRD Pamphlet no. 18: Administered cumulated activity for ventilation studies.
AB  - There has been no consensus on a standard calculational approach regarding the
      concept of administered activity in ventilation studies involving inhaled
      radioisotope gas or radioaerosols. This is caused in part by a lack of knowledge
      regarding the actual activity that enters the lung space (as opposed to activity
      introduced into the delivery system) and to the extended administration times
      (t(a)) associated with delivery protocols. METHODS: This pamphlet reviewed the
      three primary ventilation procedures, including rebreathing-system protocols,
      continuous-flow generator output techniques, and radioaerosol delivery systems.
      RESULTS: For each technique, an analytic expression has been derived for a new
      parameter called lung administered cumulated activity, A(L)(0,t(a)), which is the
      cumulated activity in the lungs during the administration phase. In addition,
      another potentially useful parameter has been defined-the mean administered
      activity for ventilation procedures, which normalizes the administered cumulated
      activity in the lung over the administration period and may serve to standardize
      descriptions of protocols between patients and institutions. Examples are
      provided that illustrate these new concepts for typical ventilation protocol
      administration parameters. CONCLUSION: The models presented can be employed to
      evaluate lung administered cumulated activity for use in ventilation dose
      estimate reports as a function of explicit variables (e.g., spirometer volume,
      generator output rate, wash-in half-time, administration time). In practice, it
      is recommended that dose estimate reports be based on measurements of cumulated
      activity in the lung over the administration period and normalized to this
      administered cumulated activity.

PMID- 11337533
TI  - Quantitative gated SPECT.

PMID- 11337534
TI  - Nuclear translocation of somatostatin analogs.

PMID- 11337535
TI  - What is the best strategy to treat and study patients after near-total
      thyroidectomy?

PMID- 11337536
TI  - A combined PET/CT scanner: the choices.

PMID- 11337537
TI  - Erythema multiforme reaction to sestamibi.

PMID- 11337538
TI  - Regional cerebral blood flow response to oral amphetamine challenge in healthy
      volunteers.
AB  - Functional brain imaging is a powerful tool for examining the central nervous
      system (CNS) response to pharmacologic challenges. Amphetamine is of interest
      both because of its role as a stimulant of the dopaminergic system and because of
      its use to alter mood in mood-disordered patients, particularly in patients
      suffering from depression. In this study, we report the effects of oral D
      amphetamine relative to placebo on regional cerebral blood flow (rCBF) measured
      by SPECT in healthy volunteers to characterize the normal CNS response to this
      primarily dopaminergic stimulant. METHODS: SPECT was used to assess changes in
      rCBF induced by amphetamine in 16 healthy volunteers. Subjects received placebo
      and then 0.4 mg/kg oral amphetamine in a fixed-order single-blind design and were
      imaged on a triple-head tomograph. Another six healthy volunteers received
      placebo at both times to assess normal rCBF variability. rCBF changes were
      assessed with a three-dimensional voxel-based analysis integrated into an
      automated coregistration system. Data were automatically normalized to whole
      brain counts and coregistered. Resultant rCBF changes were evaluated
      parametrically through the formation of an image whose voxel values were based on
      the paired t statistic. RESULTS: Amphetamine increased rCBF in two mesial
      prefrontal zones (Brodmann's areas 8 and 10), inferior orbital frontal lobe (area
      11), brain stem (ventral tegmentum), anteromesial temporal lobe (amygdala), and
      anterior thalamus. Amphetamine decreased rCBF to motor cortex, visual cortex,
      fusiform gyrus, posterolateral temporal lobe, and right lateral temporal lobe.
      CONCLUSION: Our data suggest that amphetamine induces focal increases and
      decreases in rCBF in healthy volunteers in areas primarily innervated by dopamine
      pathways and in areas with secondary (primarily limbic) affiliations. These data
      are consistent with glucose metabolic data from autoradiographic studies in
      animals, in which the largest increases are seen in brain stem, followed by
      striatum, thalamus, and frontal and sensory cortices. Frontopolar and temporal
      increases observed in our study appear to be unique to humans.

PMID- 11337539
TI  - Dynamic and static 99mTc-ECD SPECT imaging of subacute cerebral infarction:
      comparison with 133Xe SPECT.
AB  - 99mTc-ethylcysteinate dimer (99mTc-ECD) SPECT imaging reportedly fails to show
      reflow hyperemia in patients with subacute stroke. This study attempts to
      determine the clinical usefulness of dynamic 99mTc-ECD SPECT in evaluating
      regional blood flow in subacute cerebral infarction and the kinetic behavior of
      99mTc-ECD in infarct areas. METHODS: 133Xe and consecutive dynamic and static
      99mTc-ECD SPECT studies were performed on 24 patients with cortical infarction in
      the middle cerebral artery territory 13-15 d after the onset of a stroke. Image
      contrast between infarct and contralateral control areas on 99mTc-ECD tomograms
      (ECD uptake ratio) was compared with that on cerebral blood flow (CBF) images
      obtained using 133Xe inhalation (CBF ratio). RESULTS: In all cases, ECD uptake
      ratios from static images were lower than CBF ratios. This tendency was obvious
      when CBF in the infarct area increased above the normal control value, and no
      significant correlation was found between ECD uptake ratios from static images
      and CBF ratios. Only in the infarct areas with CBF below the normal control
      value, however, was a significant correlation between the two maintained (r =
      0.795; P = 0.0011). A very strong correlation was found between CBF ratios and
      ECD uptake ratios on both the first dynamic scan (36 s after injection) (r =
      0.991; P < 0.0001) and the second dynamic scan (72 s after injection) (r = 0.945;
      P < 0.0001). The correlation coefficient decreased in a time-dependent manner,
      with no significant correlation observed after the fourth dynamic scan (144 s
      after injection). On the other hand, significant correlations were observed on
      all dynamic scans only in the infarct areas with CBF below the control value.
      CONCLUSION: Super-early images of dynamic 99mTc-ECD SPECT provide a close imaging
      contrast with CBF and reveal reflow hyperemia in areas with irreversible changes
      produced by subacute stroke, which static 99mTc-ECD SPECT images fail to show.
      Decreased retention of the tracer in the infarct areas with hyperperfusion causes
      an underestimation of CBF on static 99mTc-ECD SPECT images. Given these results,
      we believe that dynamic 99mTc-ECD SPECT is an effective clinical tool to evaluate
      regional blood flow in subacute cerebral infarction.

PMID- 11337540
TI  - Statistical brain mapping of 18F-FDG PET in Alzheimer's disease: validation of
      anatomic standardization for atrophied brains.
AB  - Despite the increased use of statistical mapping to detect brain functional
      changes in Alzheimer's disease (AD), potential artifacts introduced by
      stereotactic anatomic standardization of atrophied brains have not been examined
      carefully. We investigated the effects of anatomic standardization by Statistical
      Parametric Mapping (SPM) and NEUROSTAT. METHODS: First, 10 AD patients and 10 age
      matched healthy volunteers underwent 18F-FDG brain PET imaging. Each image set
      was standardized to a stereotactic brain template using SPM or NEUROSTAT,
      followed by pixel normalization to the global or cerebellar activity. Within
      group comparisons of standardized image sets by each method and a between-group
      comparison of healthy volunteers and AD patients were performed using the
      statistical analysis routines of SPM. Second, simulated PET image sets were
      generated from segmented MR image sets of 5 healthy volunteers and 5 AD patients.
      Using the anatomic standardization parameters estimated on the simulated image
      sets, original gray matter MR image sets were transformed to the stereotactic
      coordinate system. Between-group subtraction analyses of the transformed gray
      matter image sets between healthy volunteers and AD groups were performed to
      examine the accuracy of cortical gray matter matching. RESULTS: Between-group
      comparison by SPM or NEUROSTAT showed generally similar areas of hypometabolism
      in bilateral temporoparietal, posterior cingulate, and left frontal cortices.
      Both methods showed possible deformation artifacts in the anterior part of the
      corpus callosum. The localization of the peak hypometabolism varied considerably
      between the two methods when global normalization was applied. The use of a
      common brain template for standardization resulted in asymmetric differences in
      cortical margins, indicating systematic differences in the deformation
      algorithms. The realistic simulation study revealed gray matter mismatches to be
      20% greater with SPM than with NEUROSTAT. CONCLUSION: Although different
      statistical mapping methods may yield grossly similar patterns of hypometabolism
      in AD, the extent, severity, and peak location of metabolic changes can be
      inconsistent. Deformation accuracy appears to be more prone to atrophy. These
      limitations need to be considered carefully in the application and interpretation
      of brain mapping analysis in atrophied brains.

PMID- 11337541
TI  - Relationship between the location of the most severe myocardial perfusion
      defects, the most severe coronary artery stenosis, and the site of subsequent
      myocardial infarction.
AB  - This study evaluated the relationship between the location of the most severe
      myocardial perfusion defects, the most severe coronary artery stenosis, and the
      site of subsequent acute myocardial infarction (AMI). METHODS: Of 3,180 patients
      who were admitted with a diagnosis of AMI, we identified 44 patients who had
      undergone previous myocardial perfusion SPECT. Thirty-one of them also had
      previous coronary angiography. The relationship between the location of the
      myocardial perfusion defects, the coronary artery stenosis, and the site of
      subsequent AMI was studied in these patients. RESULTS: The concordance between
      the location of the most severe reversible defects detected by SPECT and the site
      of subsequent AMI was 71% (kappa = 0.499). The concordance between the most
      severe stenosis detected by coronary angiography and the site of subsequent AMI
      was 64% (kappa = 0.451). However, kappa values for SPECT and coronary angiography
      were good when the interval between these investigations and subsequent AMI was
      <3 mo (0.724 and 0.661, respectively), for moderate to severe perfusion defects
      (0.719), and for 90%-99% coronary stenosis (0.626). CONCLUSION: The culprit
      lesion is not always the one that is manifested by the most severe reversible
      perfusion defect or the most critical coronary artery stenosis. Myocardial SPECT
      and coronary angiography can predict the location of a future AMI in 71% and 64%
      of patients, respectively. The percentage is higher when the interval between
      investigations and subsequent AMI is <3 mo, for moderate to severe perfusion
      defects, and for 90%-99% coronary stenosis.

PMID- 11337542
TI  - Interobserver reproducibility in reporting on 99mTc-DMSA scintigraphy for
      detection of late renal sequelae.
AB  - This study was designed to evaluate the interobserver variability in reporting on
      99mTc-dimercaptosuccinic acid (DMSA) scanning performed 6 mo after an acute
      episode of pyelonephritis for the detection of late renal sequelae. METHODS:
      Forty-six children were selected, who had early and late DMSA studies for
      evaluation of acute pyelonephritic lesions as well as sequelae. Three observers
      reported independently and separately on the early and late DMSA scans and, in a
      second step, on the late scan in the presence of the early scan. Interobserver
      reproducibility was evaluated for the early DMSA scan, the late DMSA scan alone,
      and the late DMSA scan with the early scan for comparison. RESULTS: Complete
      agreement between the three observers was reached in 75%, 78%, and 77% for the
      early DMSA scan, the late DMSA scan alone, and the late DMSA scan with the early
      scan for comparison, respectively. CONCLUSION: Interobserver reproducibility was
      high and was comparable for both early and late DMSA scintigraphy.

PMID- 11337543
TI  - Usefulness of 99mTc-ciprofloxacin (infecton) scan in diagnosis of chronic
      orthopedic infections: comparative study with 99mTc-HMPAO leukocyte scintigraphy.
AB  - 99mTc-labeled ciprofloxacin (infecton) has been developed for detecting
      infectious foci, which localize in high concentrations in living bacteria. Other
      studies performed with various infections in animals and humans have found that
      infecton is a promising agent with better specificity for bacterial infections
      than white blood cell (WBC) scans. In this study, we evaluated the efficacy of
      infecton scintigraphy for detecting chronic bone and joint infections. METHODS:
      Fifty-six sites with suspected bone or joint infection were examined with 99mTc
      WBC and infecton scans in 51 patients. Of these patients, 21 had prosthetic
      implant materials. Biochemical, radiologic, and microbiologic data and clinical
      outcomes also contributed, along with the results from scintigraphic techniques,
      in determining the presence or absence of infection. Scintigraphic images were
      produced at 1 and 4 h after injection of 370-400 MBq infecton or 185-200 MBq
      99mTc-hexamethylpropyleneamine oxime (HMPAO)-WBCs. For each patient, there were
      at least 2 d and at most 7 d between scintigraphic studies. RESULTS: There were
      30 true-positive, 4 false-positive, 20 true-negative, and 2 false-negative
      results with infecton. With 99mTc-HMPAO-WBCs, the results were 20, 1, 23, and 12,
      respectively. Values for sensitivity, specificity, and accuracy were 94%, 83%,
      and 89%, respectively, with the infecton scan and 63%, 96%, and 77%,
      respectively, with WBC scanning. Differences between the two agents were
      statistically significant (P < 0.001). Infecton and WBC scan results were in
      general concordance for 43 of 56 sites (77%). Infecton results for vertebral
      infections were the most notable findings in this study, despite the limited
      number of patients with this condition. Infecton scans were positive for hot
      spots in five of six patients with vertebral osteomyelitis. WBC scans showed
      photon-deficient areas in four of these same patients and normal distribution in
      the remaining two patients. CONCLUSION: Infecton is a useful agent for detecting
      infectious foci in bones and joints. Moreover, the infecton scan seems to be a
      more powerful tool in diagnosing vertebral infections than WBC scintigraphy.

PMID- 11337544
TI  - Use of 201Tl SPECT for evaluation of biologic behavior in pituitary adenomas.
AB  - Although pituitary adenomas are regarded as benign tumors, some of them behave
      aggressively with malignant behavior of invasion and metastasis. Prediction of
      such biologic behavior in a tumor is important for therapeutic planning. The
      purpose of this study was to assess the usefulness of 201Tl chloride SPECT (201Tl
      SPECT) for evaluation of biologic behavior in pituitary adenomas. METHODS: 201Tl
      SPECT was performed on 22 patients with pituitary adenomas. 201Tl uptake indices
      were calculated, and the results were compared between invasive pituitary
      adenomas and noninvasive pituitary adenomas. Correlation of the 201Tl uptake
      index and the MIB1 monoclonal antibody labeling index (MIB1 labeling index) of
      the tumors was also estimated. RESULTS: In comparison with noninvasive pituitary
      adenomas, invasive pituitary adenomas exhibited significantly higher 201Tl uptake
      indices on both the early and the delayed images (P = 0.0010 and 0.0019,
      respectively). A significant correlation was found between the 201Tl uptake index
      on the delayed image and the MIB1 labeling index (P = 0.0107). CONCLUSION: 201Tl
      SPECT can be useful for detecting biologic aggressiveness in pituitary adenomas.

PMID- 11337545
TI  - L-3-[123I]iodo-alpha-methyl-tyrosine SPECT in non-small cell lung cancer:
      preliminary observations.
AB  - L-3-[123I]iodo-alpha-methyl-tyrosine (IMT) is a modified amino acid that is
      avidly taken up by many tumors. Uptake is based on the increased transmembrane
      transport of amino acids in malignancies. IMT is the only amino acid tracer
      suitable for SPECT. The aim of this study was to determine the feasibility of IMT
      SPECT in the detection, staging, and treatment evaluation of non-small cell lung
      cancer. METHODS: We evaluated 44 IMT SPECT studies in 17 patients with
      histologically proven non-small cell lung cancer, stage III. IMT SPECT and planar
      imaging of the chest was performed before, 2 wk after, and 3 mo after 60 Gy
      radiotherapy. Staging was based on the findings of bronchoscopy, chest CT,
      mediastinoscopy, or explorative thoracotomy. After radiotherapy, CT and
      bronchoscopy were repeated to assess tumor response. RESULTS: In 15 of 16
      evaluable primary tumors, avid IMT uptake was present (sensitivity, 94%), with a
      mean (+/-SD) tumor-to-background ratio (T/B) of 2.95 +/- 0.78 (range, 1.7-4.9).
      In 12 of 14 patients (86%) with mediastinal involvement, IMT SPECT detected one
      or more mediastinal metastases. However, only 13 of 20 mediastinal metastases
      were detected in lesion analysis (lesion-based sensitivity, 65%). For lesions < 2
      cm in diameter, sensitivity was 42%. FDG PET (available for 5 patients) detected
      more known and unknown lesions than did IMT SPECT. After radiotherapy, T/B had
      fallen to 1.84 +/- 0.29 (P < 0.001 vs. baseline), and 3 mo later to 1.61 +/- 0.41
      (not statistically significant vs. second study). Considerable nonspecific uptake
      was found in irradiated normal lung tissue (mean ratio to nonirradiated tissue,
      1.79 +/- 0.53), persisting for > 3 mo. No relationship was observed between
      various IMT uptake parameters and the presence of residual viable tumor tissue or
      survival. CONCLUSION: IMT SPECT has a high sensitivity for the detection of
      primary non-small cell lung cancer. Although patient-based sensitivity in
      detecting mediastinal spread was adequate, sensitivity for individual lesions,
      especially for small metastases (<2 cm in diameter) was too low to be clinically
      helpful. Radiotherapy caused considerable nonspecific IMT uptake, which also
      limits applicability in evaluating the results of treatment.

PMID- 11337546
TI  - Impact of 18F-FDG PET on managing patients with colorectal cancer: the referring
      physician's perspective.
AB  - Whole-body PET imaging with 18F-FDG has been used successfully to stage
      colorectal cancer. However, the impact of FDG PET on patient management from the
      referring physician's point of view has not been determined. METHODS: A
      questionnaire was sent to referring physicians to determine whether and how PET
      altered the management of colorectal cancer patients. Management changes, when
      present, were classified as intermodality (e.g., medical to surgical, surgical to
      radiation, medical to no treatment) or intramodality (e.g., altered medical,
      surgical, or radiotherapy approach). RESULTS: Of 60 responses from referring
      physicians, changes in clinical stage were reported for 25 patients (42%). Among
      these, the disease was upstaged in 20 patients (80%) and downstaged in 5 patients
      (20%). The PET findings contributed to intermodality management changes in 22 of
      the 60 patients (37%), intramodality changes in 11 patients (18%), a combination
      of management changes in 4 patients (7%), and no change in 19 patients (32%). Two
      of the 60 patients (3%) had other changes, and no response to this question was
      received for the remaining 2 patients (3%). As a result of PET findings,
      physicians avoided major surgery in 41% of patients for whom surgery was the
      intended treatment. CONCLUSION: This survey-based study of referring physicians
      shows that FDG PET had a major impact on the management of colorectal cancer
      patients and contributed to changes in clinical stage and major management
      decisions in >40% of patients.

PMID- 11337547
TI  - Increased metabolic activity in the thymus gland studied with 18F-FDG PET: age
      dependency and frequency after chemotherapy.
AB  - This study was designed to evaluate the age dependency of 18F-FDG uptake in the
      thymus and the frequency of PET confirmation of thymus hyperplasia after
      chemotherapy in cancer patients. METHODS: Whole-body FDG PET recordings of 168
      patients were retrospectively examined for a retrosternal lesion in the anterior
      mediastinum that was attributable to the thymus. The patients were assigned to
      the following four groups: children with malignant lesions before the first
      therapy (group Ia; n = 15; mean age +/- SD, 11.9 +/- 3.7 y), children with
      malignant disease after chemotherapy (group Ib; n = 12; mean age, 10.3 +/- 5.0
      y), adults with histologically confirmed malignant lymphoma before the first
      therapy (group IIa; n = 37; mean age, 43.9 +/- 16.7 y), and adult lymphoma
      patients 3 wk to 4 mo after chemotherapy (group IIb; n = 104; mean age, 40.9 +/-
      14.6 y). RESULTS: Increased FDG accumulation in the thymus was seen in 11
      patients (73%) of group Ia and 9 patients (75%) of group Ib. Thymus hyperplasia
      was found in 5 patients (5%) of group IIb. The eldest of these 5 patients was 25
      y old. No increased FDG accumulation in the thymus was observed in any of the
      group IIa patients. In cases of visible FDG uptake in the thymus, standardized
      uptake values did not exceed 4. CONCLUSION: FDG accumulation in the thymus is a
      common finding in children and can occasionally be observed in young adults after
      chemotherapy. Knowledge of the characteristics of a typical retrosternal lesion
      in conjunction with the clinical history allows avoidance of diagnostic
      uncertainty and unnecessary procedures.

PMID- 11337548
TI  - Methylxanthine sensitization of human colon cancer cells to 186Re-labeled
      monoclonal antibody.
AB  - Tumor cells lacking the functional p53 suppressor gene may arrest at the G2 phase
      of the cell cycle after exposure to ionizing radiation, resulting in increased
      radioresistance. Methylxanthines (MTXs), such as pentoxifylline (PTX) or caffeine
      (CAF), can inhibit the G2-phase checkpoint arrest of damaged cells and thus
      radiosensitize them. However, the effect of MTX in cells irradiated with low-dose
      rate beta-emission is not well understood. METHODS: A clonogenic assay was
      performed with LS180 human colon cancer cells lacking the functional p53
      suppressor gene. Cells were irradiated with increasing concentrations of 186Re
      mercaptoacetyltriglycine (186Re-MAG3)-labeled A7 monoclonal antibody against
      colorectal cancer (0-925 kBq/mL) at 37 degrees C in 5% CO2 for 24 h in the
      presence or absence of PTX (0-2 mmol/L) or CAF (0-5 mmol/L). The enhancement
      ratio (ER) with MTX was calculated as a ratio of 50% cell-killing concentration
      of 186Re-MAG3-A7 in control cells to that in cells treated with PTX or CAF. The
      cell cycle distribution was analyzed with a flow cytometer. RESULTS: The
      concentration of 50% cell kill was 474 kBq/mL 186Re-MAG3-A7. Both PTX and CAF
      dose dependently enhanced the cytotoxicity of 186Re-MAG3-A7: ERs of 0.5 mmol/L
      PTX, 2 mmol/L PTX, 1 mmol/L CAF, and 5 mmol/L CAF were 1.50, 2.18, 1.54, and
      2.63, respectively. Flow cytometry showed that the percentage nonirradiated cells
      in the G2/M phase of the cell cycle was 11.3% +/- 1.66%. On the other hand, cells
      exposed to 186Re-MAG3-A7 accumulated in the G2/M phase of the cell cycle (40.2%
      +/- 1.46%), which was inhibited by the presence of 1 mmol/L PTX (19.8% +/- 8.12%)
      or 2 mmol/L CAF (26.9% +/- 6.21%). CONCLUSION: Cellular modulation of the cell
      cycle with PTX and CAF radiosensitized LS180 colon cancer cells exposed to 186Re
      radiation.

PMID- 11337549
TI  - Whole-body hybrid PET with 18F-FDG in the staging of non-Hodgkin's lymphoma.
AB  - PET with a double-head gamma camera (hybrid PET) is a new approach to tumor
      imaging with 18F-FDG. This study was conducted to clarify the feasibility of
      whole-body FDG hybrid PET in the staging of non-Hodgkin's lymphoma (NHL) in
      comparison with PET with a dedicated camera (dedicated PET) and to compare the
      results of both FDG studies with those of CT and 67Ga scanning as conventional
      imaging studies (CIS). METHODS: Thirty patients with NHL were prospectively
      evaluated. The results of the imaging studies regarding detection of the sites
      involved and staging were compared with each other and with those of the
      reference standard based on the final overall clinical evaluation. RESULTS: Of
      the total of 206 sites, whole-body FDG hybrid PET and dedicated PET detected 159
      sites (77.2%) and 179 sites (86.9%), respectively. Eighteen of the 20 sites
      missed by hybrid PET alone consisted of lesions < 1.5 cm. Both FDG studies
      provided concordant staging results in all but 2 patients. CIS, on the other
      hand, detected 164 (79.6%) of the 206 sites, 137 of which were also detected by
      hybrid PET. Hybrid PET detected an additional 22 sites not found by CIS, whereas
      CIS detected 27 additional sites. Hybrid PET and CIS provided concordant staging
      results in 19 patients. Hybrid PET correctly staged NHL in 5 additional patients,
      whereas CIS correctly staged NHL in only 1 additional patient. CONCLUSION: Whole
      body FDG hybrid PET appeared to be an accurate method of staging NHL. Despite its
      poorer image quality compared with dedicated PET, hybrid PET provided NHL staging
      results comparable with those of dedicated PET. Hybrid PET also yielded results
      comparable with those of CIS. However, whole-body FDG hybrid PET is currently
      inadequate as a single modality for staging NHL and is complementary to CT.

PMID- 11337550
TI  - FDG PET imaging in patients with lymphoma: a clinical perspective.

PMID- 11337551
TI  - Brain SPECT in neurology and psychiatry.
AB  - Structural and functional images of the brain play an important role as powerful
      adjuncts in the management of an increasing number of neurologic and psychiatric
      diseases. Brain SPECT, in particular, with perfusion agents or with neuroreceptor
      imaging radiopharmaceuticals, is rapidly becoming a clinical tool in many places.
      For many neurologic and psychiatric conditions, this imaging modality has been
      used in diagnosis, prognosis assessment, evaluation of response to therapy, risk
      stratification, detection of benign or malignant viable tissue, and choice of
      medical or surgical therapy. The importance of this technique in nuclear medicine
      today should not be overlooked, particularly in cerebrovascular diseases,
      dementias, epilepsy, head injury, malignant brain tumors, movement disorders,
      obsessive-compulsive disorder, Gilles de la Tourette's syndrome, schizophrenia,
      depression, panic disorder, and drug abuse.

PMID- 11337552
TI  - Feasibility of a high-speed gamma-camera design using the high-yield-pileup-event
      recovery method.
AB  - Higher count-rate gamma cameras than are currently used are needed if the
      technology is to fulfill its promise in positron coincidence imaging,
      radionuclide therapy dosimetry imaging, and cardiac first-pass imaging. The
      present single-crystal design coupled with conventional detector electronics and
      the traditional Anger-positioning algorithm hinder higher count-rate imaging
      because of the pileup of gamma-ray signals in the detector and electronics. At an
      interaction rate of 2 million events per second, the fraction of nonpileup events
      is < 20% of the total incident events. Hence, the recovery of pileup events can
      significantly increase the count-rate capability, increase the yield of imaging
      photons, and minimize image artifacts associated with pileups. A new technology
      to significantly enhance the performance of gamma cameras in this area is
      introduced. METHODS: We introduce a new electronic design called high-yield
      pileup-event-recovery (HYPER) electronics for processing the detector signal in
      gamma cameras so that the individual gamma energies and positions of pileup
      events, including multiple pileups, can be resolved and recovered despite the
      mixing of signals. To illustrate the feasibility of the design concept, we have
      developed a small gamma-camera prototype with the HYPER-Anger electronics. The
      camera has a 10 x 10 x 1 cm NaI(Tl) crystal with four photomultipliers. Hot-spot
      and line sources with very high 99mTc activities were imaged. The phantoms were
      imaged continuously from 60,000 to 3,500,000 counts per second to illustrate the
      efficacy of the method as a function of counting rates. RESULTS: At 2-3 million
      events per second, all phantoms were imaged with little distortion, pileup, and
      dead-time loss. At these counting rates, multiple pileup events (> or = 3 events
      piling together) were the predominate occurrences, and the HYPER circuit
      functioned well to resolve and recover these events. The full width at half
      maximum of the line-spread function at 3,000,000 counts per second was 1.6 times
      that at 60,000 counts per second. CONCLUSION: This feasibility study showed that
      the HYPER electronic concept works; it can significantly increase the count-rate
      capability and dose efficiency of gamma cameras. In a larger clinical camera,
      multiple HYPER-Anger circuits may be implemented to further improve the imaging
      counting rates that we have shown by multiple times. This technology would
      facilitate the use of gamma cameras for radionuclide therapy dosimetry imaging,
      cardiac first-pass imaging, and positron coincidence imaging and the simultaneous
      acquisition of transmission and emission data using different isotopes with less
      cross-contamination between transmission and emission data.

PMID- 11337553
TI  - Merging the instrumentation evolution.

PMID- 11337554
TI  - COMKAT: compartment model kinetic analysis tool.
AB  - Compartment models are the basis for most physiologically based quantification of
      nuclear medicine data. Although some software packages are available for this
      purpose, many are expensive, run on relatively few types of computers or are of
      limited capability, and cannot be extended because of the unavailability of
      source code. Consequently, institutions with modeling expertise often develop
      software for themselves, which has the disadvantages of lack of standardization
      and possible replication of effort. Therefore, general-purpose compartment
      modeling software distributed with source code would be a welcome resource for
      the nuclear medicine community. METHODS: We formulated a mathematic framework
      within which compartment models containing unimolecular and bimolecular (receptor
      saturation) kinetics can be described. We implemented this framework within
      MATLAB and call the resultant software COMKAT (Compartment Model Kinetic Analysis
      Tool). RESULTS: COMKAT simplifies the process of defining and solving standard
      blood flow, 18F-FDG, and receptor models as well as models of a user's own
      design. In particular, COMKAT automatically defines and implements state,
      analytic sensitivity, and Jacobian equations. Given these, COMKAT can perform
      simulations in which model outputs are solved for specified parameter values,
      thereby allowing the user to predict how sensitive data are to these parameters.
      In addition, COMKAT can be used to estimate values for the parameters by fitting
      model output to experimental data. COMKAT is equipped with command-line and
      graphic user interfaces from which the user can access these features. Examples
      of these applications are presented along with validation and performance
      summaries. CONCLUSION: COMKAT is a useful software tool and is available without
      cost to researchers, at www.nuclear.uhrad.com/comkat.

PMID- 11337555
TI  - In vitro and in vivo tracer characteristics of an established multidrug-resistant
      human colon cancer cell line.
AB  - 99mTc-methoxyisobutylisonitrile (99mTc-MIBI) has been suggested as a tracer for
      the scintigraphic detection of multidrug resistance (MDR). The aim of this study
      was to compare MDR characteristics in vitro and in vivo by immunohistochemic and
      functional uptake assays in established tumor cell lines cultured and grown in
      severe combined immunodeficient (SCID) mice. METHODS: The presence of MDR was
      assessed in vitro in drug-resistant HT-29(mdr1) colon carcinoma cells and in
      nonresistant HT-29(par) cells by JSB-1 immunohistochemistry, uptake of the
      fluorescent dye Rhodamine 123, and quantitative measurement of 99mTc-MIBI
      accumulation. For in vivo imaging, SCID mice bearing subcutaneous xenografts of
      these cell lines were injected with 99mTc-MIBI and 18F-FDG for scintigraphic and
      PET examination. After imaging, tumors were analyzed by immunohistochemistry and
      electron microscopy. RESULTS: All HT-29(mdr1) cells cultured in vitro exhibited
      distinct JSB-1 immunoreactivity, although to a variable degree, whereas HT
      29(par) cells were completely devoid of JSB-1 staining. Rhodamine 123 accumulated
      poorly in HT-29(mdr1) cells but strongly in HT-29(par) cells. Accumulation of
      99mTc-MIBI was 0.05% +/- 0.01% of the activity of the external medium in HT
      29(mdr1) cells, but about eight times higher in HT-29(par) cells (0.40% +/-
      0.09%), a very low percentage compared with other tumor cell lines. No difference
      in 201TlCl accumulation was observed between both cell lines. In vivo, neither HT
      29(par) nor HT-29(mdr1) tumors grown in SCID mice could be detected by 99mTc-MIBI
      scintigraphy. In FDG PET, both HT-29(mdr1) and HT-29(par) tumors were clearly
      visible. FDG uptake was, however, markedly higher in HT-29(par) than in HT
      29(mdr1) tumors. Both tumor types were poorly vascularized, as shown
      histologically. JSB-1 immunoreactivity was absent in all HT-29(par) tumors
      examined, whereas the majority of HT-29(par) tumor cells were stained. Electron
      microscopy showed that HT-29(par) tumors contained significantly less
      mitochondria than hepatocytes of the SCID mouse liver, which displayed high 99mTc
      MIBI uptake in our scintigraphy studies. CONCLUSION: Sufficient 99mTc-MIBI uptake
      is the major prerequisite for distinguishing successfully between drug-resistant
      and sensitive cells. Negative 99mTc-MIBI scintigrams are not necessarily
      associated with MDR expression. In some tumors, FDG may be an in vivo marker for
      MDR as suggested by PET.

PMID- 11337556
TI  - Tumor uptake of copper-diacetyl-bis(N(4)-methylthiosemicarbazone): effect of
      changes in tissue oxygenation.
AB  - We showed previously that, in vitro, copper-diacetyl-bis(N(4)
      methylthiosemicarbazone) (Cu-ATSM) uptake is dependent on the oxygen
      concentration (pO2). We also showed that, in vivo, Cu-ATSM uptake is
      heterogeneous in animal tumors known to contain hypoxic fractions. This study was
      undertaken to confirm the pO2 dependence of this selective uptake in vivo by
      correlating Cu-ATSM uptake with measured tumor pO2. METHODS: Experiments were
      performed with the 9L gliosarcoma rat model using a needle oxygen electrode to
      measure tissue pO2. Using PET and electronic autoradiography, Cu-ATSM uptake was
      measured in tumor tissue under various pO2 levels. The oxygen concentration
      within implanted tumors was manipulated by chemical means or by altering the
      inhaled oxygen content. RESULTS: A good correlation between low pO2 and high Cu
      ATSM accumulation was observed. Hydralazine administration in animals caused a
      decrease in the average tumor pO2 from 28.61 +/- 8.74 mm Hg to 20.81 +/- 7.54 mm
      Hg in untreated control animals breathing atmospheric oxygen. It also caused the
      tumor uptake of Cu-ATSM to increase by 35%. Conversely, in animals breathing 100%
      oxygen, the average tumor pO2 increased to 45.88 +/-15.9 mm Hg, and the tumor
      uptake of Cu-ATSM decreased to 48% of that of the control animals. PET of animals
      treated in a similar fashion yielded time-activity curves showing significantly
      higher retention of the tracer in hypoxic tissues than in oxygenated tissues.
      CONCLUSION: These data confirm that Cu-ATSM uptake in tissues in vivo is
      dependent on the tissue pO2, and that significantly greater uptake and retention
      occur in hypoxic tumor tissue. Therefore, the possible use of Cu-ATSM PET as a
      prognostic indicator in the management of cancer is further validated.

PMID- 11337557
TI  - Monte Carlo MCNP-4B-based absorbed dose distribution estimates for patient
      specific dosimetry.
AB  - This study was intended to verify the capability of the Monte Carlo MCNP-4B code
      to evaluate spatial dose distribution based on information gathered from CT or
      SPECT. METHODS: A new three-dimensional (3D) dose calculation approach for
      internal emitter use in radioimmunotherapy (RIT) was developed using the Monte
      Carlo MCNP-4B code as the photon and electron transport engine. It was shown that
      the MCNP-4B computer code can be used with voxel-based anatomic and physiologic
      data to provide 3D dose distributions. RESULTS: This study showed that the MCNP
      4B code can be used to develop a treatment planning system that will provide such
      information in a time manner, if dose reporting is suitably optimized. If each
      organ is divided into small regions where the average energy deposition is
      calculated with a typical volume of 0.4 cm(3), regional dose distributions can be
      provided with reasonable central processing unit times (on the order of 12-24 h
      on a 200-MHz personal computer or modest workstation). Further efforts to provide
      semiautomated region identification (segmentation) and improvement of marrow dose
      calculations are needed to supply a complete system for RIT. It is envisioned
      that all such efforts will continue to develop and that internal dose
      calculations may soon be brought to a similar level of accuracy, detail, and
      robustness as is commonly expected in external dose treatment planning.
      CONCLUSION: For this study we developed a code with a user-friendly interface
      that works on several nuclear medicine imaging platforms and provides timely
      patient-specific dose information to the physician and medical physicist. Future
      therapy with internal emitters should use a 3D dose calculation approach, which
      represents a significant advance over dose information provided by the standard
      geometric phantoms used for more than 20 y (which permit reporting of only
      average organ doses for certain standardized individuals)

PMID- 11337558
TI  - Biodistribution and dosimetry of pretargeted monoclonal antibody 2D12.5 and Y
      Janus-DOTA in BALB/c mice with KHJJ mouse adenocarcinoma.
AB  - Biodistribution and dosimetry of 88Y (and equimolar 90Y) Janus
      dodecanetetraacetic acid (DOTA) were performed using a three-step pretargeting
      protocol in BALB/c mice bearing mouse mammary adenocarcinoma (KHJJ) implants.
      Pretargeting was performed with mouse monoclonal antibody (mAb) 2D12.5 specific
      for yttrium-DOTA, and the chase was Y-DOTA-human transferrin conjugate. In this
      article, we report extensive organ dosimetry and the theoretic limits of the
      radionuclide physical half-life (T(p)) for pretargeting. METHODS: Organ
      biodistribution data were obtained from bioassays on tissue taken from tumor mice
      killed at 3, 24, 48, 72, 96, and 120 h after intravenous injection of 88Y-Janus
      DOTA. Uptake and retention of 88Y as a function of time were described by
      nonlinear least squares fits of the tissue data to multiexponential functions.
      Radiation dose estimates for equivalent molar amounts of 90Y were subsequently
      derived from these time-integrated functions. RESULTS: The results were as
      follows: rapid blood clearance of 88Y-Janus-DOTA; rapid uptake and slow clearance
      of 88Y-Janus-DOTA from the tumor over 5 d; rapid clearance from all organs and
      body; largest radiation absorbed dose (AD) per injected dose of 63.52 (cGy/MBq)
      to tumor; high therapeutic ratios (AD tumor/AD tissue), particularly for blood
      and bone; and optimal radionuclide T(p) range from 30 min to 10 d. CONCLUSION:
      Although the absolute concentration of 90Y in the tumor is less using the hapten
      system than is achieved generally with the chelated radionuclide covalently
      attached to the mAb, the achievable tumor uptake of radioactivity, coupled with
      low radioactivity in bone, blood, and other organs, suggests that a three-step
      pretargeting protocol has considerable promise as a method for 90Y
      radioimmunotherapy.

PMID- 11337559
TI  - [18F]fluoroestradiol radiation dosimetry in human PET studies.
AB  - [18F]16alpha-fluoroestradiol (FES) is a PET imaging agent useful for the study of
      estrogen receptors in breast cancer. We estimated the radiation dosimetry for
      this tracer using data obtained in patient studies. METHODS: Time-dependent
      tissue concentrations of radioactivity were determined from blood samples and PET
      images in 49 patients (52 studies) after intravenous injection of FES. Radiation
      absorbed doses were calculated using the procedures of the MIRD committee, taking
      into account the variation in dose based on the distribution of activities
      observed in the individual patients. Effective dose equivalent was calculated
      using International Commission on Radiological Protection Publication 60 weights
      for the standard woman. RESULTS: The effective dose equivalent was 0.022 mSv/MBq
      (80 mrem/mCi). The organ that received the highest dose was the liver (0.13
      mGy/MBq [470 mrad/mCi]), followed by the gallbladder (0.10 mGy/MBq [380
      mrad/mCi]) and the urinary bladder (0.05 mGy/MBq [190 mrad/mCi]). CONCLUSION: The
      organ doses are comparable to those associated with other commonly performed
      nuclear medicine tests. FES is a useful estrogen receptor-imaging agent, and the
      potential radiation risks associated with this study are well within accepted
      limits.

PMID- 11337560
TI  - Are leukocytes labeled with stabilized 99mTc-HMPAO becoming activated during
      labeling?

PMID- 11337561
TI  - Quantitative assessment of motion artifacts and validation of a new motion
      correction program for myocardial perfusion SPECT.
AB  - Patient motion during myocardial perfusion SPECT can produce images that show
      artifactual perfusion defects. The relationship between the degree of motion and
      the extent of artifactual perfusion defects is not clear for either single- or
      double-head detectors. Using both single- and double-head detectors and
      quantitative perfusion SPECT (QPS) software, we studied the pattern and extent of
      defects induced by simulated motion and validated a new automatic motion
      correction program for myocardial perfusion SPECT. METHODS: Vertical motion was
      simulated by upward shifting of the raw projection datasets in a returning
      pattern (bounce) and in a nonreturning pattern at 3 different phases of the SPECT
      acquisition (early, middle, and late), whereas upward creep was simulated by
      uniform shifting throughout the acquisition. Lateral motion was similarly
      simulated by left shifting of the raw projection datasets in a returning pattern
      and in a nonreturning pattern. Simulations were performed using single- and
      double-head detectors, and simulated motion was applied to projection images from
      8 patients who had normal 99mTc-sestamibi SPECT findings. Additionally, images
      from 130 patients with actual clinical motion were assessed before and after
      motion correction. The extent of perfusion defects was assessed by QPS, and a 20
      segment, 5-point scoring system was used to assess the effect of motion on the
      presence and extent of perfusion defects. RESULTS: Of 12 bounce simulations, the
      bouncing motion failed to produce significant (>3%) perfusion defects with either
      the single- or the double-head detector. With the single-head detector, early
      shifting created the largest defect, whereas with the double-head detector,
      shifting during the middle of the acquisition created the largest defect. With
      regard to upward creep, defects were of larger extent with the double- than the
      single-head detector. With the single-head detector, 8 of 20 simulated motion
      patterns yielded significant perfusion defects of the left ventricle, 7 (88%) of
      which were significantly improved after motion correction. With the double-head
      detector, 12 of 20 patterns yielded significant defects, all of which improved
      significantly after correction. Of 2,600 segments in the 130 patients with actual
      clinical motion, only 1.3% (30/2,259) of segments that were considered normal
      (score = 0 or 1) changed to abnormal (score = 2-4) after motion correction,
      whereas 27% (92/341) of abnormal segments were reclassified as normal after
      motion correction. CONCLUSION: Artifactual perfusion defects created by simulated
      motion are a function of the time, degree, and type of motion and the number of
      camera detectors. Application of an automatic motion-correction algorithm
      effectively decreases motion artifacts on myocardial perfusion SPECT images.

PMID- 11337562
TI  - Reproducibility of an automatic quantitation of regional myocardial wall motion
      and systolic thickening on gated 99mTc-sestamibi myocardial SPECT.
AB  - We investigated the reproducibility of an automatic quantitative algorithm for
      measuring regional myocardial wall motion and systolic thickening. METHODS: 99mTc
      sestamibi gated myocardial SPECT with dipyridamole stress was performed twice
      consecutively on 31 patients with known or suspected coronary artery disease,
      with the patients in the same position for each scan. With AutoQUANT software,
      segmental wall motion and systolic thickening were quantified automatically and
      expressed in millimeters and percentage increase, respectively, for 20 segments.
      Afterward, the correlation and agreement between repeated measurements were
      investigated, and the influences of wall location, perfusion grade, and
      partitioning of the myocardium on reproducibility were evaluated by ANOVA and t
      testing. RESULTS: High correlations (r = 0.95 for wall motion and 0.88 for
      systolic thickening) and good agreements (weighted kappa = 0.81 and 0.71,
      respectively) were obtained from repeated measurements on consecutive gated
      SPECT. Changes in wall location and perfusion grade did not cause significant
      differences between repeated measurements (P > 0.05 in ANOVA and t testing), but
      a change in partitioning did. On Bland-Altman analysis, 2 SDs for repeated wall
      motion and for systolic thickening were 2.0 mm and 20%, respectively. CONCLUSION:
      The automatic quantitative algorithm for myocardial SPECT provided by AutoQUANT
      software has good reproducibility under diverse conditions. A change of motion >
      2.0 mm or a change of systolic thickening > 20% can be regarded as significant
      during a follow-up study using this software.

PMID- 11337563
TI  - Comparison of 2-dimensional and 3-dimensional cardiac 82Rb PET studies.
AB  - Most new PET scanners have the capability to collect data in 3-dimensional (3D)
      (septa removed) mode. This allows many more detected events at the cost of
      increased random events and scatter. In the case of 82Rb imaging, the injected
      dose might have to be limited to avoid saturating the scanner. We present a
      comparison of 2-dimensional (2D) and 3D data collection for 82Rb cardiac studies
      using the ECAT EXACT scanner. METHODS: Resting 82Rb cardiac studies were
      collected in 2D and 3D modes for 33 consecutive patients. Four experienced
      physicians rated the images to determine if the different acquisition methods
      would lead to different patient care. A separate quantitative analysis was
      performed on data from multiple scans of a thoracic phantom filled to simulate
      cardiac and background radioactivity corresponding to 82Rb injections between 37
      and 1740 MBQ: RESULTS: The 2D and 3D studies were significantly different, with
      the image quality being poorer in the 3D studies. The scanner collected data at
      near its maximal counting rate for either 1480-MBq 2D or 37-MBq 3D acquisitions.
      Because the data collection was counting rate limited in either mode, and there
      are more random and scatter events in 3D mode, the 2D acquisitions resulted in
      more detected true events and a better signal-to-noise ratio. CONCLUSION: Cardiac
      82Rb studies should be performed in 2D mode when using the ECAT EXACT scanner.

PMID- 11337564
TI  - Absolute changes in regional cerebral blood flow in association with upright
      posture in humans: an orthostatic PET study.
AB  - To determine whether hemodynamic parameters are changed by upright posture in
      healthy middle-aged humans, absolute values of regional cerebral blood flow
      (rCBF) were investigated for three different orthostatic conditions. METHODS: PET
      with [15O]H2O and arterial blood sampling were performed on eight middle-aged
      healthy volunteers while they were sitting passively or standing actively.
      Absolute rCBF values estimated by the autoradiographic method in regions of
      interest were compared using ANOVA, and relative changes in rCBF were also
      analyzed voxel by voxel using statistical parametric mapping (SPM). RESULTS:
      Physiologic data remained unchanged for different conditions. ANOVA and SPM
      showed that absolute and relative rCBF levels were significantly elevated in the
      cerebellar vermis in the standing position compared with those in the supine and
      sitting positions. In contrast, ANOVA showed that rCBF in the frontal and
      parietal cortices tended to be lower in the sitting and standing positions than
      in the supine position. Regression analysis showed that the frontal rCBF measured
      during standing tended to be inversely correlated with age. CONCLUSION: The
      results showed that cerebellar vermis activation was more marked in the standing
      position than in the sitting or supine positions, indicating that the vermis is a
      neural substrate for controlling voluntary upright posture. Brain perfusion in
      the distal internal carotid artery region may be subject to orthostatic postural
      changes in healthy middle-aged humans.

PMID- 11337565
TI  - Dynamic PET 18F-FDG studies in patients with primary and recurrent soft-tissue
      sarcomas: impact on diagnosis and correlation with grading.
AB  - The purpose of this study was to evaluate (18)F-FDG PET studies of primary and
      recurrent sarcomas for diagnosis and correlation with grading. METHODS: The
      evaluation included 56 patients, 43 with histologically proven malignancies and
      13 with benign lesions. Seventeen patients were referred with suspicion on a
      primary tumor, and the remaining 39 were referred with suspicion on a recurrent
      tumor. The FDG studies were accomplished as a dynamic series for 60 min. The
      evaluation of the FDG kinetics was performed using the following parameters:
      standardized uptake value (SUV), global influx, computation of the transport
      constants K1-k4 with consideration of the distribution volume (VB) according to a
      two-tissue-compartment model, and fractal dimension based on the box-counting
      procedure (parameter for the inhomogeneity of the tumors). RESULTS: Visual
      evaluation revealed a sensitivity of 76.2%, a specificity of 42.9%, and an
      accuracy of 67.9%. The vascular fraction VB and the SUV were higher in malignant
      tumors compared with benign lesions (t test, P < 0.05). Although the FDG SUV
      helped to distinguish benign and malignant tumors, there was some overlap, which
      limited the diagnostic accuracy. The SUV and fractal dimension accounted for
      significant differences in six of the nine diagnostic pairs. Whereas grade (G) II
      and G III tumors were differentiated from lipomas on the basis of the fractal
      dimension and some other kinetic parameters, no differences were found between G
      I tumors and lipomas. On the basis of the discriminant analysis, the
      differentiation of soft-tissue tumors was best for the use of six parameters of
      the FDG kinetics (SUV, VB, K1, k3, influx, and fractal dimension). Eighty-four
      percent of G III tumors, 37.5% of G II tumors, 80% of G I tumors, 50% of lipomas,
      and 14.3% of scars could be classified correctly, whereas inflammatory lesions
      were misclassified. CONCLUSION: FDG PET should be used preferentially for
      monitoring patients with G III sarcomas. Visual analysis provides a low
      specificity. In contrast, the evaluation of the full FDG kinetics provides
      superior information, particularly for the discrimination of G I and G III tumors
      (positive predictive value, >80%).

PMID- 11337566
TI  - Ki-67 immunostaining in pancreatic cancer and chronic active pancreatitis: does
      in vivo FDG uptake correlate with proliferative activity?
AB  - PET with 18F-FDG has been shown to be useful in the detection and staging of
      pancreatic cancer. However, whether FDG uptake is dependent on proliferative
      activity is still unclear. The aim of this prospective study was to evaluate a
      probable correlation between FDG uptake and proliferative activity in benign and
      malignant pancreatic tumors. METHODS: Our series consisted of 23 patients with
      pancreatic cancer and 9 patients with chronic active pancreatitis (CAP). FDG PET
      was performed within 2 wk before surgery, and standardized uptake values (SUVs)
      were calculated for benign and malignant pancreatic tumors. Patients were
      selected when focally increased FDG uptake in previously known pancreatic tumors
      was present. Proliferation fraction was measured in tissue specimens using the
      anti-Ki-67 antibody MIB-1. A computer-assisted imaging system was used for
      quantification of nuclear Ki-67 immunostaining. Immunohistochemical findings were
      correlated to SUVS: RESULTS: Pancreatic cancer showed both intense nuclear
      staining of Ki-67 (39% +/- 16%) and high FDG uptake (SUV = 3.6 +/- 1.6). However,
      no significant correlation was found between in vivo FDG uptake and Ki-67
      immunoreactivity (P = 0.65). By contrast, Ki-67 nuclear staining was
      significantly lower (3.8% +/- 2.7%, P < 0.05) in CAP, whereas FDG uptake was in
      the same range as for pancreatic cancer (SUV = 3.5 +/- 1.8). CONCLUSION: FDG
      uptake did not correlate with proliferative activity in pancreatic cancer.
      Proliferative activity was tenfold higher in malignant pancreatic tumors than in
      benign tumors associated with CAP, whereas FDG uptake in vivo did not differ
      significantly. Thus, a PET tracer indicating cellular proliferation should better
      differentiate between cancer and inflammatory lesions than do metabolic markers
      such as FDG.

PMID- 11337567
TI  - Production and characterization of 188Re-C595 antibody for radioimmunotherapy of
      transitional cell bladder cancer.
AB  - Bladder cancer was responsible for >12,000 deaths in the United States in 1999.
      The high-molecular-weight glycoprotein MUC1 mucin is overexpressed on bladder
      tumors and represents a useful target for radioimmunoscintigraphy and
      radioimmunotherapy. We report on the production and initial tracer studies of a
      188Re-antibody complex directed against this target and intended for intravesical
      radioimmunotherapy of superficial bladder cancer. METHODS: 188Re perrhenate was
      eluted from a 188W/188Re generator. C595 antibody was reduced with 2
      mercaptoethanol and was labeled in the presence of stannous tartrate. The final
      reaction mixture contained high-molecular-weight contamination, which was removed
      from the complex using an affinity separation technique. The specificity and
      integrity of the antibody complex were tested by radioimmunoassay and size
      exclusion chromatography. Tumor localization was investigated using an ex vivo
      model in human cystectomy specimens. Tracer amounts of the complex were also
      administered intravesically to three patients with bladder cancer, who were then
      imaged by gamma scintigraphy. RESULTS: The complex was immunoreactive (70% +/-
      17%) and specific for MUC1 antigens. A peak corresponding to a protein of 150 kDa
      was observed on size exclusion chromatography, showing that the complex was
      homogeneous. Binding to bladder tumors was observed in an ex vivo model in which
      tumors were successfully imaged in four specimens. The mean tumor-to-normal
      tissue ratio in ex vivo bladders was 7:1. Tumor uptake after intravesical
      administration was confirmed in three patients with bladder cancer (mean tumor-to
      normal tissue ratio, 4:1). CONCLUSION: The C595 antibody was labeled with 188Re,
      providing a radioimmunoconjugate with high immunoreactivity and specificity. Its
      ability to localize in tumors both in an ex vivo model and after intravesical
      administration to patients has been shown. This approach will now be extended for
      the therapy of superficial bladder cancer.

PMID- 11337568
TI  - Receptor measurements via Tc-GSA kinetic modeling are proportional to functional
      hepatocellular mass.
AB  - Kinetic modeling of 99mTc-diethylenetriaminepentaacetic acid galactosyl human
      serum albumin (Tc-GSA) measures the total amount of asialoglycoprotein receptor
      within a subject's liver. This study tested the hypothesis that the amount of
      asialoglycoprotein receptor measured by Tc-GSA modeling provides a valid index of
      functional liver mass. METHODS: Twenty-two patients with cirrhosis, 18 patients
      with chronic hepatitis, and 9 patients with normal liver parenchyma were studied
      with Tc-GSA using a 30-min dynamic imaging protocol. The total amount of hepatic
      receptor was measured by kinetic modeling of the Tc-GSA time-activity data. The
      total number of viable hepatocytes was calculated using standard morphometric
      measurements of liver biopsy samples and liver volume measurements through CT.
      RESULTS: The total receptor amount strongly correlated with the total hepatocyte
      number (r = 0.803; P < 0.0001). CONCLUSION: Tc-GSA measurement of the total
      receptor amount is proportional to the number of viable hepatocytes and therefore
      provides a valid assessment of functional liver mass.

PMID- 11337569
TI  - Salivary and lacrimal gland dysfunction (sicca syndrome) after radioiodine
      therapy.
AB  - Salivary gland dysfunction has been described in patients undergoing radioiodine
      therapy but associated lacrimal gland dysfunction (sicca syndrome) has never been
      reported. We conducted a prospective cohort study with follow-up for up to 3 y in
      a tertiary care university center to determine the prevalence of sicca syndrome
      in patients after high-dose radioiodine treatment. METHODS: From January 1990 to
      December 1995, all patients undergoing radioiodine therapy (n = 79) with a
      standard dose of 925 MBq to 18.5 GBq (25-500 mCi) were interviewed using a
      standardized questionnaire to determine subjective ocular and oral dryness and
      were examined for objective lacrimal and salivary gland dysfunction. RESULTS:
      After radioiodine treatment, 32.9% of the patients reported subjective xerostomia
      and 25.3% reported subjective xerophthalmia in the first year of follow-up.
      Xerostomia persisted to the second year of follow-up in 20.3% of cases and was
      still present >3 y after the last dose of radioiodine in 15.2% of cases.
      Xerophthalmia persisted to the second year of follow-up in 17.7% of cases and was
      still present in the third year of follow-up in 13.9% of cases. Severe xerostomia
      occurred in 4 patients. Reduced salivary and lacrimal gland function was
      documented in 40 (50.6%) and 14 (17.7%) of the 79 cases, respectively, in the
      first year of follow-up. Objective xerostomia persisted in 13.9% of cases to the
      second year of follow-up and was still present in all patients >3 y after the
      last radioiodine application. Keratoconjunctivitis sicca persisted in 11 patients
      (13.9%) to the second year of follow-up but was only present in 6 patients (7.6%)
      >3 y after the last radioiodine application. Additionally, 28/79 patients (35.4%)
      who had a normal salivary gland scintigraphy previously showed reduced salivary
      gland function in the third year of follow-up. No significant dependence on
      cumulative treatment was found for objective xerostomia or xerophthalmia, but
      doses >11.1 GBq (300 mCi) were related to stage 3 dysfunction on salivary gland
      scintigraphy. CONCLUSION: Salivary and lacrimal gland dysfunction (sicca
      syndrome) is relatively frequent after radioiodine therapy. In most cases this is
      a transient side effect, but in some patients it may persist for a long period or
      appear late.

PMID- 11337570
TI  - Inhalation of [123I]alpha1-protease inhibitor: toward a new therapeutic concept
      of alpha1-protease inhibitor deficiency?
AB  - The alpha1-protease inhibitor (alpha1-Pi) is separated from human serum and is
      therefore extremely expensive. Because only 2%-3% concentrates in the lung after
      intravenous administration, inhalational therapy for alpha1-Pi deficiency would
      seem likely to be better. The aims of this study were therefore to determine the
      pattern of deposition of inhaled alpha1-Pi labeled with 123I and measure the
      amount deposited in the lungs. METHODS: Eighteen patients with congenital severe
      alpha1-Pi deficiency were enrolled in the study. The low-specific-activity 123I
      labeled alpha1-Pi aerosol (median particle size +/- SD, 3.9 +/- 2.5 microm) was
      generated by an air pressure-driven nebulizer. The patients inhaled for an
      average of 23.6 +/- 8.9 min. Static scintigrams in two projections were acquired
      immediately after (T1) and 1 (T2), 4 (T3), and 24 h (T4) after inhalation. The
      patients were divided into the following three groups according to their forced
      expiratory volume in 1 s (FEV1): group I, < or =40% of predicted normal (n = 8);
      group II, 40% < FEV1 < or = 60% of predicted normal (n = 4); group III, >60% of
      predicted normal (n = 6). RESULTS: The absolute percentage uptake values of
      alpha1-Pi in group I were 12.4 for T1, 7.3 for T2, 4.6 for T3, and 1.2 for T4; in
      group II the values were 13.0, 9.6, 6.2, and 2.0, respectively; and in group III,
      14.6, 11.4, 6.5, and 3.6, respectively. Differences between the groups were
      generally statistically significant. Between T1 and T2, the probability value was
      <0.05 for group I versus group II, <0.006 for group I versus group III, and <0.39
      for group II versus group III. Between T1 and T3, the probability value was <0.29
      for group I versus group II, <0.22 for group I versus group III, and <0.94 for
      group II versus group III. Retention (between T1 and T4) was also dependent on
      the grade of the disease: P < 0.2 for group I versus group II, P < 0.001 for
      group I versus group III, and P < 0.02 for group II versus group III. Grading of
      the uptake pattern by three independent experienced investigators (87% agreement)
      revealed a peripheral deposition that was group dependent. We found that greater
      peripheral deposition corresponded with lower lung functional impairment: P < 0.5
      for group I versus group II, P < 0.01 for group I versus group III, and P < 0.08
      for group II versus group III. Degradation also corresponded with functional
      impairment: P < 0.05 for group I versus group II, P < 0.006 for group I versus
      group III, and P < 0.3 for group II versus group III. CONCLUSION: The results of
      this study show that sufficient amounts of alpha1-Pi can be deposited in the
      periphery of the lung by inhalation at least in patients with low-grade disease.
      Inhalation of alpha1-Pi may thus represent a new and more convenient route of
      drug administration.

PMID- 11337571
TI  - Uptake of cis-4-[18F]fluoro-L-proline in urologic tumors.
AB  - Tumor uptake of the amino acid cis-4-[18F]fluoro-L-proline (cis-FPro) was studied
      with PET in eight patients with urologic tumors. METHODS: Three patients had
      primary renal cell carcinomas (RCCs), one had a local recurrence of RCC, one had
      squamous RCC, one had an adrenal hemangioma, one had inguinal metastases of
      penile squamous carcinoma, and one had suspected metastatic disease from prostate
      cancer. PET scans of the trunk were acquired at 1 and 3-5 h after intravenous
      injection of 400 MBq cis-FPro and compared with 18F-FDG PET scans and CT.
      RESULTS: None of the tumors or metastases showed significant uptake of cis-FPro.
      FDG uptake was seen in one of the three primary RCCs, in the local recurrence of
      RCC, in the squamous RCC, and in the metastases of penile cancer. CONCLUSION: Cis
      FPro appears not to be a promising PET tracer in oncology.

PMID- 11337572
TI  - An introduction to PET and SPECT neuroreceptor quantification models.
AB  - PET and SPECT using appropriate radioligands allow imaging of certain critical
      components of neurotransmission such as presynaptic transporters and postsynaptic
      receptors in living human brains. PET and SPECT data are commonly analyzed by
      applying tracer kinetic models. These modeling approaches assume a compartmental
      system and derive the outcome measure called the binding potential, which
      reflects the densities of transporters or receptors in a brain region of
      interest. New models are often noninvasive in that they do not require arterial
      blood sampling. In this review, the concept and principles of tracer kinetic
      modeling are introduced and commonly used PET and SPECT neuroreceptor
      quantification models are discussed.

PMID- 11337573
TI  - Immuno-PET of human colon xenograft- bearing BALB/c nude mice using 124I-CDR
      grafted humanized A33 monoclonal antibody.
AB  - Radiolabeling monoclonal antibodies (mAbs) allows the evaluation of
      biodistribution of constructs in vivo through gamma camera imaging and also
      permits quantitation of mAb uptake in tumors through biopsy-based counting
      techniques. The quantitation of radiolabeled mAb uptake in cancer patients is
      complicated by the attenuation of gamma emissions of routinely used isotopes
      (e.g., 131I and 111In) and the spatial resolution and sensitivity of gamma
      cameras. METHODS: We used the positron-emitting isotope 124I (half-life [T1/2] =
      4.2 d) to label the recombinant humanized anti-colorectal cancer A33 antibody
      (huA33) and evaluated its biodistribution properties and PET imaging
      characteristics in BALB/c nude mice bearing SW1222 colorectal xenografts and
      control colon tumors. RESULTS: The immunoreactivity of radioconjugate was 78% as
      determined using the cell-binding Lindmo assay. The apparent association constant
      was found to be 2.2 x 10(9) M(-1), and the number of antibody binding sites per
      cell was 371,000. The radioconjugate was found to be stable in serum obtained
      from mice at various times after injection. Assuming a two-compartment model with
      a four-parameter fit of mean blood levels, the T1/2alpha was 1.5 h and the
      T1/2beta was 38.2 h. Excellent tumor uptake was obtained, with maximal uptake
      reaching 50.0 +/- 7.0 percentage injected dose per gram of tumor by 4 d after
      injection. Specificity of localization was shown by lack of uptake in control
      tumor. PET imaging detected antigen-positive tumor by 4 h after injection, and
      high-resolution images were obtained by 24 h after injection. CONCLUSION: In
      clinical trials using PET, huA33 labeled with 124I has potential for imaging and
      staging colon tumors and quantifying antibody uptake in colon tumors in vivo.

PMID- 11337574
TI  - PET imaging for planning cancer therapy.

PMID- 11337575
TI  - Absolute quantification of regional myocardial uptake of 99mTc-sestamibi with
      SPECT: experimental validation in a porcine model.
AB  - We have evaluated a method for absolute in vivo quantification of 99mTc-sestamibi
      uptake in a porcine model of myocardial perfusion. METHODS: Correlated CT and
      radionuclide images were obtained from eight adult pigs using a combined CT-SPECT
      imaging system. In each case, the CT image is used to generate an object-specific
      attenuation map that is incorporated into an iterative algorithm for
      reconstruction and attenuation correction of the radionuclide image. Anatomic
      information available from the correlated CT image is used to correct the
      radionuclide image for partial-volume errors by mathematically modeling the
      radionuclide imaging process. A volume of interest, or template, that
      approximates the geometric extent of the myocardium is defined from the CT image.
      Once defined, the template is assigned unit activity and is mathematically
      projected using a realistic physical model of the radionuclide imaging process
      including nonideal collimation and object-specific attenuation. The template is
      then reconstructed from these projections to obtain a pixel-by-pixel partial
      volume correction for the myocardium in the radionuclide image. The CT image is
      also used to delimit the anatomic boundaries of the myocardium for quantification
      of the radionuclide images. The pixel intensities in the corrected radionuclide
      image are calibrated in units of activity concentration (MBq/g) and compared with
      the ex vivo activity concentration measured directly from the excised myocardium.
      RESULTS: Without corrections, the measured in vivo activity concentration in the
      porcine myocardium was only 10% of the true value. Correcting for object-specific
      attenuation improved the accuracy of this measurement but resulted in values that
      were still only 42% of the true value. By correcting for both attenuation and
      partial-volume errors, we were able to achieve absolute quantification with an
      accuracy error near 10%. CONCLUSION: We have shown that, by applying object
      specific attenuation corrections and suitable partial-volume corrections,
      absolute regional activity concentration can be measured accurately in the
      porcine myocardium.

PMID- 11337576
TI  - The road to quantitation of regional myocardial uptake of tracer.

PMID- 11337577
TI  - Quantification of regional myocardial blood flow using dynamic H2(15)O PET and
      factor analysis.
AB  - Because the use of factor analysis has been proposed for extracting pure
      physiologic temporal or spatial information from dynamic nuclear medicine images,
      factor analysis should be capable of robustly estimating regional myocardial
      blood flow (rMBF) using H2(15)O PET without additional C15O PET, which is a
      cumbersome procedure for patients. Therefore, we measured rMBF using time
      activity curves (TACs) obtained from factor analysis of dynamic myocardial
      H2(15)O PET images without the aid of C15O PET. METHODS: H2(15)O PET of six
      healthy dogs at rest and during stress was performed simultaneously with
      microsphere studies using 85Sr, 46Sc, and 113SN: We performed factor analysis in
      two steps after reorienting and masking the images to include only the cardiac
      region. The first step discriminated each factor in the spatial distribution and
      acquired the input functions, and the second step extracted regional-tissue TACS:
      Image-derived input functions obtained by factor analysis were compared with
      those obtained by the sampling method. rMBF calculated using a compartmental
      model with tissue TACs from the second step of the factor analysis was compared
      with rMBF measured by microsphere studies. RESULTS: Factor analysis was
      successful for all the dynamic H2(15)O PET images. The input functions obtained
      by factor analysis were nearly equal to those obtained by arterial blood
      sampling, except for the expected delay. The correlation between rMBF obtained by
      factor analysis and rMBF obtained by microsphere studies was good (r = 0.95). The
      correlation between rMBF obtained by the region-of-interest method and rMBF
      obtained by microsphere studies was also good (r = 0.93). CONCLUSION: rMBF can be
      measured robustly by factor analysis using dynamic myocardial H2(15)O PET images
      without additional C15O blood-pool PET.

PMID- 11337578
TI  - 99mTc-labeled antimicrobial peptides for detection of bacterial and Candida
      albicans infections.
AB  - This study compared the possibilities and limitations of 99mTc-labeled synthetic
      peptides derived from two human antimicrobial peptides, namely, ubiquicidin (UBI)
      and lactoferrin (hLF), for the scintigraphic detection of bacterial and fungal
      infections in mice and rabbits. The rationale of our approach was that selected
      peptides accumulate in infected areas but not in sterile inflammatory lesions,
      because they bind preferentially to microorganisms. 99mTc-labeled human
      neutrophil peptides (defensins), ciprofloxacin, and human polyclonal IgG were
      included as control agents. METHODS: 99mTc-labeled peptides and control agents
      were injected intravenously into animals that had been injected intramuscularly
      18 h earlier with multidrug-resistant Staphylococcus aureus, Klebsiella
      pneumoniae, or fluconazole-resistant Candida albicans. Sterile inflammatory sites
      were induced by the injection of heat-killed microorganisms or lipopolysaccharide
      (LPS) into the thigh muscle. Up to 4 h after injection, the accumulation of 99mTc
      labeled compounds in the infected/inflamed thigh muscles was determined using
      scintigraphic techniques and radioactivity counts in dissected tissues. RESULTS:
      Scintigraphy revealed that 99mTc-labeled peptides UBI 29-41, UBI 18-35, UBI 31
      38, hLF 1-11, and defensins, which showed preferential in vitro binding to
      microorganisms in a former study, accumulated at a significantly higher rate (P <
      0.01) in bacterial and C. albicans infections in mice and rabbits than in
      inflamed tissues induced by heat-killed microorganisms or by LPS. No significant
      difference in the accumulation of 99mTc-labeled ciprofloxacin was observed
      between infected and sterile inflamed thigh muscles in mice. CONCLUSION: 99mTc
      labeled antimicrobial peptides UBI 29-41, UBI 18-35, UBI 31-38, hLF 1-11, and
      defensins accumulate significantly in tissues infected with gram-positive and
      gram-negative bacteria and C. albicans. Significantly lower (P < 0.01)
      accumulation of these peptides occurs in sterile inflamed tissues. These data
      indicate that the peptides preferentially tag microorganisms at the site of
      infection, which is in agreement with their preferential binding to the
      microorganisms in vitro and in vivo. 99mTc-labeled ciprofloxacin does not
      distinguish between infections and sterile inflammatory lesions, which implies
      that its specificity for the detection of bacterial infections is not warranted.

PMID- 11337579
TI  - Liver kinetics of glucose analogs measured in pigs by PET: importance of dual
      input blood sampling.
AB  - Metabolic processes studied by PET are quantified traditionally using
      compartmental models, which relate the time course of the tracer concentration in
      tissue to that in arterial blood. For liver studies, the use of arterial input
      may, however, cause systematic errors to the estimated kinetic parameters,
      because of ignorance of the dual blood supply from the hepatic artery and the
      portal vein to the liver. METHODS: Six pigs underwent PET after [15O]carbon
      monoxide inhalation, 3-O-[11C]methylglucose (MG) injection, and [18F]FDG
      injection. For the glucose scans, PET data were acquired for 90 min. Hepatic
      arterial and portal venous blood samples and flows were measured during the scan.
      The dual-input function was calculated as the flow-weighted input. RESULTS: For
      both MG and FDG, the compartmental analysis using arterial input led to
      systematic underestimation of the rate constants for rapid blood-tissue exchange.
      Furthermore, the arterial input led to absurdly low estimates for the
      extracellular volume compared with the independently measured hepatic blood
      volume of 0.25 +/- 0.01 mL/mL (milliliter blood per milliliter liver tissue). In
      contrast, the use of a dual-input function provided parameter estimates that were
      in agreement with liver physiology. Using the dual-input function, the clearances
      into the liver cells (K1 = 1.11 +/- 0.11 mL/min/mL for MG; K1 = 1.07 +/- 0.19
      mL/min/mL for FDG) were comparable with the liver blood flow (F = 1.02 +/- 0.05
      mL/min/mL). As required physiologically, the extracellular volumes estimated
      using the dual-input function were larger than the hepatic blood volume. The
      linear Gjedde-Patlak analysis produced parameter estimates that were unaffected
      by the choice of input function, because this analysis was confined to time
      scales for which the arterial-input and dual-input functions were very similar.
      CONCLUSION: Compartmental analysis of MG and FDG kinetics using dynamic PET data
      requires measurements of dual-input activity concentrations. Using the dual-input
      function, physiologically reasonable parameter estimates of K1, k2, and Vp were
      obtained, whereas the use of conventional arterial sampling underestimated these
      parameters compared with independent measurements of hepatic flow and hepatic
      blood volume. In contrast, the linear Gjedde-Patlak analysis, being less
      informative but more robust, gave similar parameter estimates (K, V) with both
      input functions.

PMID- 11337580
TI  - Metabolism of 99mTc-ethylcysteinate dimer in infarcted brain tissue of rats.
AB  - Brain SPECT with 99mTc-ethylcysteinate dimer (99mTc-ECD) reveals a subacute
      cerebral infarct as a hypoactive area, even in the presence of postischemic
      hyperperfusion. The brain retention of 99mTc-ECD depends on hydrophilic
      conversion mediated by enzymes, and impaired enzymatic trapping is hypothesized
      to depress the retention efficiency in the infarcted region. The aim of this
      study was to determine whether the metabolic rate of 99mTc-ECD is actually
      reduced in infarcted brain tissue. METHODS: In 50 mmol/L phosphate buffer (pH
      7.4), 99mTc-ECD was incubated for 30 min with homogenates of rat brain tissue
      with and without triphenyltetrazolium chloride (TTC) staining. The ratio of polar
      products was determined by thin-layer chromatography as a function of incubation
      time, and metabolic rates were obtained. Permanent focal ischemia was induced by
      occlusion of the right middle cerebral artery (MCA) in rats. The brain was
      removed 24 h after MCA occlusion, and the infarcted area was defined by TTC
      staining. The metabolic rate of 99mTc-ECD was determined in homogenates of
      infarcted tissue, contralateral noninfarcted tissue, and tissue sampled from sham
      operated rats. The infarct volume was measured by direct and indirect methods to
      assess volume expansion caused by edema, and the metabolic rate in infarcted
      tissue was corrected for the effect of edema. RESULTS: TTC staining had no effect
      on the metabolic rate of 99mTc-ECD. The metabolic rates in the infarcted tissue
      were 0.222%/min +/- 0.054%/min and 0.285%/min +/- 0.064%/min before and after
      correction for edema, respectively. These rates were significantly lower than
      those in the contralateral noninfarcted tissue (0.426%/min +/- 0.028%/min) and
      the tissue sampled from the sham-operated rats (0.439%/min +/- 0.031%/min). No
      substantial difference in rates was observed between the contralateral tissue and
      the tissue from the sham-operated rats. CONCLUSION: The results of this study
      showed that infarction decreases the activity of enzymes that mediate the
      hydrophilic conversion of 99mTc-ECD in the brain and suggest that reduced
      metabolic activity is related to decreased accumulation of 99mTc-ECD in
      hyperperfused infarcts.

PMID- 11337581
TI  - Experimental and clinical evaluation of iterative reconstruction (OSEM) in
      dynamic PET: quantitative characteristics and effects on kinetic modeling.
AB  - The purpose of this study was to investigate the quantitative properties and
      effects of ordered-subset expectation maximization (OSEM) on kinetic modeling
      compared with filtered backprojection (FBP) in dynamic PET studies. Both phantom
      and patient studies were performed. METHODS: For phantom studies dynamic two
      dimensional emission scans with 10-min frames and 20-min scan intervals were
      acquired over a 14-h period using an HR+ PET scanner. Various phantoms were
      scanned: 2-, 5-, 10-, and 20-cm-diameter phantoms filled with an 18F solution
      (300 kBq/mL) and a NEMA phantom filled with an 18F background (40 kBq/mL) and a
      cold or 11C insert (450 kBq/mL). Transmission (Tx) scans of 5-60 min were
      acquired. Data were reconstructed using FBP Hanning 0.5 and OSEM with 2-12
      iterations and 12 or 24 subsets. Quantitative accuracy and noise characteristics
      were assessed. For patient studies, five cardiac, three oncologic, and three
      brain dynamic 18F-FDG scans were used. Five reconstructions were performed: FBP
      Hanning 0.5, and OSEM 2 x 12 and OSEM 4 x 16 with and without 5-mm full width at
      half maximum smoothing. Time-activity curves were calculated using volumes of
      interest. The input function was derived from arterial sampling. Metabolic rate
      of glucose (MRglu) was calculated with a standard two-tissue compartment model
      and Patlak analysis. RESULTS: Contribution of Tx noise to the reconstructed image
      was smaller for OSEM than for FBP. Differences in signal-to-noise ratio between
      FBP and OSEM depended on number of iterations and phantom size. Bias with OSEM
      was observed for regions enclosed within a 5- to 10-fold hotter background. For
      cardiac studies OSEM 2 x 12 and OSEM 4 x 16 resulted in 13% and 21% higher pixel
      values and 9% and 15% higher MRglu values compared with FBP. Smoothing decreased
      all these values to 2%. Similar results were found for most tumor studies. For
      brain studies MRglu of FBP and OSEM 4 x 16 agreed within 2%. Use of OSEM image
      derived input functions for cardiac PET studies resulted in a decrease in
      calculated MRglu of about 15%. CONCLUSION: For most PET studies OSEM has equal
      quantitative accuracy as FBP. The higher pixel and MRglu values are explained by
      the better resolution of OSEM. However, OSEM does not provide accurate image
      derived input functions for FDG cardiac PET studies because of bias in regions
      located within a hotter background.

PMID- 11337582
TI  - Comparison of sestamibi, tetrofosmin, and Q12 retention in porcine myocardium.
AB  - Although there are several 99mTc perfusion tracers introduced for clinical use,
      there are no data available directly comparing these tracers with microsphere
      determined flow. The aim of this study was to compare the myocardial retention of
      sestamibi, tetrofosmin, and Q12 in a porcine model. METHODS: We used a pig model
      with (n = 6) or without (n = 3) coronary occlusion. Each pig received a
      simultaneous injection of sestamibi and either tetrofosmin (group 1, n = 5) or
      Q12 (group 2, n = 4) labeled with either 99mTc or 95mTc (physical half-life, 61
      d; photon energy, 204 keV) during pharmacologic vasodilation. Absolute myocardial
      retention of each tracer was calculated from the myocardial tracer activity and
      arterial input function. RESULTS: The plot of all three tracers versus flow
      achieved a plateau at a higher flow range. However, sestamibi showed a higher
      mean retention than either tetrofosmin (group 1, 0.27 +/- 0.11 vs. 0.16 +/- 0.06
      mL/g/min, respectively; P < 0.01) or Q12 (group 2, 0.32 +/- 0.13 vs. 0.09 +/-
      0.03 mL/g/min, respectively; P < 0.01). Furthermore, when a linear regression
      analysis was performed to assess the relationship between retention and
      microsphere-determined flow, sestamibi showed a greater increment in retention
      than did tetrofosmin or Q12. CONCLUSION: Although all of the tracers showed a
      nonlinear increase in retention as flow increased, sestamibi may display more
      favorable characteristics as a flow tracer in the porcine heart.

PMID- 11337583
TI  - Clinical skills in conducting research studies on clinical applications of
      oncologic PET.

PMID- 11337584
TI  - Optimized mammary lymphoscintigraphy using larger colloid particles.

PMID- 11337585
TI  - "Yellow eluate" from a 99mTc generator.

PMID- 11337586
TI  - Evidence for substantial variations of atmospheric hydroxyl radicals in the past
      two decades.
AB  - The hydroxyl radical (OH) is the dominant oxidizing chemical in the atmosphere.
      It destroys most air pollutants and many gases involved in ozone depletion and
      the greenhouse effect. Global measurements of 1,1,1-trichloroethane (CH3CCl3,
      methyl chloroform) provide an accurate method for determining the global and
      hemispheric behavior of OH. Measurements show that CH3CCl3 levels rose steadily
      from 1978 to reach a maximum in 1992 and then decreased rapidly to levels in 2000
      that were lower than the levels when measurements began in 1978. Analysis of
      these observations shows that global OH levels were growing between 1978 and
      1988, but the growth rate was decreasing at a rate of 0.23 +/- 0.18% year(-2), so
      that OH levels began declining after 1988. Overall, the global average OH trend
      between 1978 and 2000 was -0.64 +/- 0.60% year(-1). These variations imply
      important and unexpected gaps in current understanding of the capability of the
      atmosphere to cleanse itself.

PMID- 11337587
TI  - Interactions of the COP9 signalosome with the E3 ubiquitin ligase SCFTIRI in
      mediating auxin response.
AB  - The COP9 signalosome is an evolutionary conserved multiprotein complex of unknown
      function that acts as a negative regulator of photomorphogenic seedling
      development in Arabidopsis. Here, we show that plants with reduced COP9
      signalosome levels had decreased auxin response similar to loss-of-function
      mutants of the E3 ubiquitin ligase SCFTIR1. Furthermore, we found that the COP9
      signalosome and SCFTIR1 interacted in vivo and that the COP9 signalosome was
      required for efficient degradation of PSIAA6, a candidate substrate of SCFTIR1.
      Thus, the COP9 signalosome may play an important role in mediating E3 ubiquitin
      ligase-mediated responses.

PMID- 11337588
TI  - Promotion of NEDD-CUL1 conjugate cleavage by COP9 signalosome.
AB  - SCF ubiquitin ligases control various processes by marking regulatory proteins
      for ubiquitin-dependent proteolysis. To illuminate how SCF complexes are
      regulated, we sought proteins that interact with the human SCF component CUL1.
      The COP9 signalosome (CSN), a suppressor of plant photomorphogenesis, associated
      with multiple cullins and promoted cleavage of the ubiquitin-like protein NEDD8
      from Schizosaccharomyces pombe CUL1 in vivo and in vitro. Multiple NEDD8-modified
      proteins uniquely accumulated in CSN-deficient S. pombe cells. We propose that
      the broad spectrum of activities previously attributed to CSN subunits--including
      repression of photomorphogenesis, activation of JUN, and activation of p27
      nuclear export--underscores the importance of dynamic cycles of NEDD8 attachment
      and removal in biological regulation.

PMID- 11337589
TI  - Linearly polarized emission from colloidal semiconductor quantum rods.
AB  - Colloidal quantum rods of cadmium selenide (CdSe) exhibit linearly polarized
      emission. Empirical pseudopotential calculations predict that slightly elongated
      CdSe nanocrystals have polarized emission along the long axis, unlike spherical
      dots, which emit plane-polarized light. Single-molecule luminescence spectroscopy
      measurements on CdSe quantum rods with an aspect ratio between 1 and 30 confirm a
      sharp transition from nonpolarized to purely linearly polarized emission at an
      aspect ratio of 2. Linearly polarized luminescent chromophores are highly
      desirable in a variety of applications.

PMID- 11337596
TI  - The value of P.

PMID- 11337598
TI  - It's time to rehabilitate the P-value.

PMID- 11337599
TI  - Low P-values or narrow confidence intervals: which are more durable?

PMID- 11337600
TI  - Of P-values and Bayes: a modest proposal.

PMID- 11337601
TI  - Multiple sclerosis and antecedent infections.

PMID- 11337602
TI  - Non-hormonal contraception and the risk of ovarian cancer.

PMID- 11337603
TI  - Multiple sclerosis and age at infection with common viruses.
AB  - Increased risk of multiple sclerosis has been reported among individuals with a
      history of measles and other common childhood diseases during adolescence,
      infectious mononucleosis, or exposure to the canine distemper virus. We
      investigated these associations in a case-control study nested within the Nurses'
      Health Study (121,700 women traced since 1976) and the Nurses' Health Study II
      (116,671 women traced since 1989). Age at diagnosis of common viral diseases and
      birth order were obtained through a questionnaire. Our results include 301 cases
      with multiple sclerosis and their (up to six) matched controls. Except for
      infectious mononucleosis, which was a moderate risk factor (odds ratio = 2.1, 95%
      confidence interval = 1.5-2.9), we found little association between history of
      common viral diseases or exposure to canine distemper virus and risk of multiple
      sclerosis. We did find a relation between mumps after 15 years of age (odds ratio
      = 2.3, 95% confidence interval = 1.2-4.3) or measles after age 15 years of age
      (odds ratio = 2.8, 95% confidence interval = 0.8-9.1) and multiple sclerosis.
      Birth order was not materially related to multiple sclerosis. Our findings
      support the hypothesis that individuals who suffered from infectious
      mononucleosis, a marker of late infection with the Epstein-Barr virus, have an
      increased risk of multiple sclerosis. Late infection with other common viruses
      may also be associated with increased risk.

PMID- 11337604
TI  - Oral contraceptives, other methods of contraception, and risk reduction for
      ovarian cancer.
AB  - Oral contraceptives reduce the risk of ovarian cancer, but the impact of other
      methods of contraception has not been fully explored. This population-based, case
      control study involved women 20-69 years of age who had ever had intercourse. We
      compared cases with a recent diagnosis of ovarian cancer (N = 727) with community
      controls (N = 1,360). All methods of contraception evaluated were associated with
      a reduced risk for ovarian cancer. After adjustment for age, race, pregnancies,
      and family history of ovarian cancer, the odds ratios for ever-use of each method
      as compared with never-use were: oral contraceptives for contraception, 0.6 (95%
      confidence interval = 0.5-0.8); intrauterine device, 0.8 (95% confidence interval
      = 0.6-1.0); barrier methods, 0.8 (95% confidence interval = 0.6-0.9); tubal
      ligation, 0.5 (95% confidence interval 0.4-0.7); and vasectomy, 0.8 (95%
      confidence interval = 0.6-1.1). Nulligravid women were not protected by any of
      these contraceptive methods. Multigravid women, however, were protected by all
      methods. We conclude that various methods of contraception reduce ovarian cancer
      risk. This effect does not appear to result from contraceptive use being a
      nonspecific marker of fertility. The results imply mechanisms other than hormonal
      or ovulatory by which ovarian cancer risk is reduced.

PMID- 11337605
TI  - Mortality among augmentation mammoplasty patients.
AB  - Much attention has focused on disease risks among women receiving silicone breast
      implants, but there has been little evaluation of their mortality experience. We
      undertook a retrospective cohort study of 13,488 women receiving cosmetic
      implants and 3,936 patients with other types of plastic surgery at 18 plastic
      surgery practices. After an average of 13 years of follow-up, deficits in overall
      mortality were found as compared with the general population (U.S. rates) for
      both implant [255 deaths; standardized mortality ratio (SMR) = 0.69, 95%
      confidence interval (CI) = 0.6-0.8] and comparison subjects (125 deaths; SMR =
      0.58, 95% CI = 0.5-0.7). These findings indicate that patients seeking plastic
      surgery are in general healthier than their peers. Implant patients, however,
      experienced excess risks of death compared with the general population for brain
      cancer (SMR = 2.45) and suicide (SMR = 1.54). Internal analyses showed a higher
      overall mortality among the implant than among the comparison patients (relative
      risk = 1.27, 95% CI = 1.0-1.6). This overall excess reflected increases for
      respiratory tract (SMR = 3.03) and brain (SMR = 2.25) cancers and for suicide
      (SMR = 4.24).

PMID- 11337606
TI  - The association between air pollution and heart failure, arrhythmia, embolism,
      thrombosis, and other cardiovascular causes of death in a time series study.
AB  - In a time series study, air pollution was associated with specific cardiovascular
      causes of death. Deaths due to heart failure (ICD-9 428), arrhythmia (ICD-9 427),
      cerebrovascular causes (ICD-9 430-436), and thrombocytic causes (ICD-9 415.1, 433
      4, 444, 452-3) were more strongly associated with air pollution than
      cardiovascular deaths (ICD-9 390-448) in general. Excess relative risks were 2.5
      to 4 times larger for these categories than for total cardiovascular disease
      mortality. Heart failure deaths, which made up 10% of all cardiovascular deaths,
      were found to be responsible for about 30% of the cardiovascular deaths related
      to particulate matter, SO2, CO, and NO2.

PMID- 11337607
TI  - Opportunities for population-based studies of complex genetic disorders after the
      human genome project.

PMID- 11337615
TI  - Scoliosis and its pathophysiology: do we understand it?

PMID- 11337616
TI  - The efficacy of direct current stimulation for lumbar intertransverse process
      fusions in an animal model.
AB  - STUDY DESIGN: Posterolateral lumbar intertransverse process fusion using a rabbit
      model with autologous bone graft and direct current stimulation was compared with
      fusion achieved by using autologous bone graft alone. OBJECTIVES: To determine
      the efficacy of direct current electrical stimulation for the posterolateral
      lumbar intertransverse process fusion technique by using a 20-microA current and
      the more recently developed 60-microA current delivered by an implantable direct
      current stimulator. SUMMARY OF BACKGROUND DATA: Previous studies have
      demonstrated a positive effect of direct current electrical stimulation on
      posterior spinal fusion techniques. However, until recently, the environment of
      an intertransverse fusion was not well simulated. The current research examined
      the posterolateral lumbar intertransverse process fusion technique with direct
      current electrical stimulation using a rabbit model. This appears to parallel
      human fusion techniques more closely and allows for lower cost and technical
      ease. METHODS: In this study, 44 adult New Zealand white rabbits underwent an L5
      L6 intertransverse process fusion. All the fusions used an autologous bone graft
      obtained from bilateral posterior iliac crests. A device was implanted in all the
      rabbits subcutaneously, and they were divided randomly into three groups: a sham
      or nonfunctioning group, a 20-microA low-current stimulator group, and a 60
      microA higher-current stimulator group. Spinal fusion was evaluated
      radiographically, histologically, and manually as well as by biomechanical
      testing 5 weeks after surgery. RESULTS: Radiographic grades, manual palpation,
      biomechanical strength, and stiffness showed an increasing trend from sham or
      inactive stimulator groups to low-current and then to high-current stimulator
      groups. Histologic analysis revealed that the higher-current stimulator showed
      that, statistically, the healing response of the host tissue to the autograft had
      increased significantly, as compared with the sham. CONCLUSIONS: Direct current
      electrical stimulation is efficacious in improving both the healing rate and
      strength in this posterolateral lumbar fusion model. In addition, it appears that
      this effect is enhanced by increasing the stimulation current from 20 microA to
      60 microA.

PMID- 11337618
TI  - Phenotypic inflammation switch in rats shown by calcitonin gene-related peptide
      immunoreactive dorsal root ganglion neurons innervating the lumbar facet joints.
AB  - STUDY DESIGN: The changes in dorsal root ganglion neurons innervating the L5-L6
      facet joint were studied using the retrograde neurotransport method and the
      immunohistochemistry of calcitonin gene-related peptide in an inflammatory model
      of rats. OBJECTIVES: To determine by inflammatory stimulation the changes in
      calcitonin gene-related peptide-immunoreactive dorsal root ganglion neurons
      innervating the L5-L6 facet. SUMMARY OF BACKGROUND DATA: The rat L5-L6 facet
      joint is innervated from L1-L5 dorsal root ganglia. The presence of calcitonin
      gene-related peptide-immunoreactive dorsal root ganglion neurons innervating the
      L5-L6 facet joint has been confirmed, but the changes in the number and
      distribution of these neurons caused by inflammation have not been studied.
      METHODS: Retrograde transport of fluorogold was used in 20 rats: 10 in the
      control group and 10 in the inflammatory group. Using the dorsal approach,
      fluorogold crystals were injected into the left L5-L6 facet joint. Then 5 days
      after application, complete Freund's adjuvant (50 microg Mycobacterium butyricum
      in oil saline emulsion) was injected into the same L5-L6 facet joint
      (inflammatory group). Of the total fluorogold-labeled dorsal root ganglion
      neurons from T13-L6, the number and cross-sectional area of the cell profiles of
      fluorogold-labeled, calcitonin gene-related peptide-immunoreactive neurons in the
      bilateral dorsal root ganglia of both groups were evaluated. RESULTS: Fluorogold
      labeled neurons were distributed throughout the ipsilateral dorsal root ganglia
      from L1-L5 in both groups. Of the fluorogold-labeled neurons, the ratios of the
      calcitonin gene-related peptide-immunoreactive L1, L2, L3, L4, and L5 dorsal root
      ganglion neurons, respectively, were 17%, 24%, 44%, 56%, and 50% in the control
      group and 50%, 39%, 51%, 61%, and 56% in the inflammatory group. The ratios of
      the calcitonin gene-related peptide-immunoreactive L1 and L2 dorsal root ganglion
      neurons labeled by fluorogold were significantly higher in the inflammatory group
      than in the control group (P < 0.05). The mean cross-sectional area of fluorogold
      labeled, calcitonin gene-related peptide-immunoreactive cells from L1-L5 dorsal
      root ganglia increased from 621 +/- 64 microm2 to 893 +/- 63 microm2 in the
      inflammatory group (P < 0.01). CONCLUSIONS: The ratio of fluorogold-labeled,
      calcitonin gene-related peptide-immunoreactive neurons was significantly higher
      in the L1 and L2 dorsal root ganglia of the inflammatory group than in those of
      the control group, and the average cross-sectional area of the cells from L1-L5
      dorsal root ganglion increased. Associated with the inflammation in the facet
      joints, the change in calcitonin gene-related peptide-immunoreactive neuron
      distribution and the phenotypic switch to large neurons may complicate the
      mechanism of facet joint inflammatory pain.

PMID- 11337619
TI  - Correlation between the age of pinealectomy and the development of scoliosis in
      chickens.
AB  - STUDY DESIGN: Pinealectomy induces experimental scoliosis in chickens. This study
      analyzed the correlation between the age at which pinealectomy was performed and
      the development of scoliosis in chickens. OBJECTIVE: To investigate the
      differences in the rate or magnitude of scoliosis and the type of curvature in
      chickens pinealectomized at different times after hatching. SUMMARY OF BACKGROUND
      DATA: Scoliosis develops in almost all chickens pinealectomized within 3 days
      after hatching, but there are no data on whether the condition will develop in
      chickens pinealectomized earlier or later after hatching. METHODS: In this study,
      106 female white leghorn chickens were divided into six groups: four pinealectomy
      groups (pinealectomy was performed 2, 4, 11, or 18 days after hatching in Groups
      P-2, P-4, P-11, and P-18, respectively), a control group (Group C), and a sham
      operation group (Group S). Ventrodorsal radiographs of the spine were taken at 4
      week intervals until the age of 12 weeks. At 12 weeks, a 1-mL sample of blood was
      taken from the heart at the middle of the dark cycle, and the serum melatonin
      concentration was measured by radioimmunoassay. RESULTS: At the age of 12 weeks,
      scoliosis was present in 63.6% of the chickens in Group P-2, 72.7% in Group P-4,
      81% in Group P-11, and 70% in Group P-18, and the Cobb angles in the scoliotic
      chickens averaged 32.6, 29.8, 23.8, and 22.3 degrees in the respective groups.
      There were no significant differences in the rate or magnitude of scoliosis and
      the type of curvature among the pinealectomy groups at the age of 12 weeks. At
      the age of 12 weeks, the serum melatonin levels at the middle of the dark cycle
      in the pinealectomized chickens were significantly lower than those of chickens
      in Groups C and S. However, there were no differences in the serum melatonin
      levels between scoliotic and nonscoliotic pinealectomized chickens. CONCLUSIONS:
      Findings from this study show that scoliosis develops in 60% to 80% of chickens
      pinealectomized within 18 days after hatching, and that scoliotic development is
      not influenced by the age at which pinealectomy is performed. However, this study
      suggests that melatonin plays a complicated role in spinal development, inasmuch
      as the serum melatonin levels after pinealectomy approximated zero. Yet scoliosis
      did not develop in all pinealectomized chickens.

PMID- 11337620
TI  - Pineal transplantation after pinealectomy in young chickens has no effect on the
      development of scoliosis.
AB  - STUDY DESIGN: Three experimental groups and one control group of chickens
      underwent different surgical procedures to determine the effects of pineal gland
      transplantation on the development of scoliosis. OBJECTIVE: To determine whether
      transplantation of the pineal gland to the body wall musculature maintains serum
      melatonin levels at normal values and prevents the development of scoliosis.
      SUMMARY OF BACKGROUND DATA: Scoliosis occurs consistently after pinealectomy in
      young chickens. Many characteristics of this scoliosis are similar to those seen
      in patients with adolescent idiopathic scoliosis. It is not clear whether the
      underlying mechanism is dependent on reduced levels of serum melatonin or some
      other aspect of the extensive surgery. METHODS: Four groups of chickens were
      selected: normal chickens, pinealectomized chickens, chickens that underwent
      simple cutting of the pineal stalk, and chickens that underwent transplantation
      of the pineal gland into the body wall. Development of scoliosis was determined
      from measurement of the Cobb angle from weekly radiographs. RESULTS: All of the
      experimental groups showed the same levels of incidence and the same patterns of
      scoliosis development. Serum melatonin levels were reduced to nearly zero in all
      the experimental groups for the duration of the experiment. Scoliosis developed
      in none of the normal chickens. CONCLUSIONS: Neither transplantation of the
      pineal gland into the body wall musculature nor simple cutting of the pineal
      stalk was able to maintain normal levels of serum melatonin because both
      procedures reduced levels to nearly zero. The incidence and pattern of scoliosis
      development in these groups were the same as those for the pinealectomized group.
      Reduction of serum melatonin levels remains a prerequisite for scoliosis
      development in young chickens.

PMID- 11337621
TI  - Comparison between sheep and human cervical spines: an anatomic, radiographic,
      bone mineral density, and biomechanical study.
AB  - STUDY DESIGN: The quantitative anatomic, radiographic, computerized tomographic,
      and biomechanical data of sheep and human cervical spines were evaluated.
      OBJECTIVES: To compare the anatomic, radiographic, computerized tomographic, and
      biomechanical data of human and sheep cervical spines to determine whether the
      sheep spine is a suitable model for human spine research. SUMMARY OF BACKGROUND
      DATA: Sheep spines have been used in several in vivo and in vitro experiments.
      Quantitative data of the normal sheep cervical spine are lacking, yet these data
      are crucial to discussion about the results of such animal studies. METHODS: In
      this study, 20 fresh adult female Merino sheep cervical spines and 20 fresh human
      cadaver cervical spines were evaluated anatomically, radiographically,
      computerized tomographically, and biomechanically. Three linear and two angular
      parameters were evaluated on four digital radiographic views: anteroposterior,
      right lateral in neutral position, flexion, and extension. Quantitative computed
      tomography scans at the center of each vertebral body and 3 mm below both
      endplates were analyzed for bone mineral density measurements. Biomechanical
      testing was performed in flexion, extension, axial rotation, and lateral bending
      by a nondestructive stiffness method using a nonconstrained testing apparatus.
      Range of motion and stiffness of each motion segment were calculated.
      Additionally, 10 linear anatomic parameters of each vertebra were measured using
      a digital ruler. RESULTS: Anterior and mean disc space height in the sheep
      cervical spine increased constantly from C2-C3 to C6-C7, whereas middle disc
      space height decreased and posterior disc space height remained unchanged.
      Anterior and mean disc space height were significantly higher in sheep. In both
      sheep and human cervical spines, intervertebral angles were not significantly
      different. Standard deviations of bone mineral density in the human cervical
      spine were fourfold higher than in the sheep cervical spine, yet no significant
      differences were found in bone mineral density values between the two species.
      Range of motion differed significantly between the two species except in flexion
      extension of C3-C4, C5-C6, axial rotation of C2-C3, and lateral bending of C2-C3,
      C3-C4, and C4-C5. Stiffness also was significantly different except in flexion
      extension of C2-C3, C4-C5, C5-C6, and lateral bending of C2-C3, C3-C4, and C4-C5.
      Anatomic evaluation showed no difference in upper endplate parameters for C4 and
      C5. CONCLUSIONS: Although several differences were found between human and sheep
      cervical spines, the small intergroup standard deviations and the good
      comparability with the human spine encourage the use of the sheep cervical spine
      as a model for cervical spine research. On the basis of the quantitative data
      obtained in this study, the sheep motion segment C3-C4 seemed to be the most
      reliable model for the corresponding human motion segment.

PMID- 11337622
TI  - Nonoperative treatment versus posterior fixation for thoracolumbar junction burst
      fractures without neurologic deficit.
AB  - STUDY DESIGN: A prospective clinical trial was conducted. OBJECTIVE: To compare
      the results of nonoperative treatment versus short-segment posterior fixation
      using pedicle screws. SUMMARY OF BACKGROUND DATA: A previous study showed that
      nonoperative treatment with early mobilization produced good results, even when
      the posterior column was involved. METHODS: This study involved 80 patients.
      Inclusion criteria required the following: neurologically intact patient, single
      level closed burst fracture involving T11-L2, no fracture dislocations or pedicle
      fractures, age of 18 to 65 years (nonpathologic adult), and no other major organ
      system or musculoskeletal injuries. Patients in the nonoperative group (n = 47)
      were allowed activity to the point of pain tolerance beginning on the day of
      injury using a hyperextension brace. Patients in the operative group (n = 33)
      underwent three-level, (one above, one at fracture level, and one below) fixation
      using VSP or TSRH instrumentation. The follow-up period was 2 years. RESULTS: The
      surgical group had less pain up to 3 months and a better Greenough Low Back
      Outcome Score up to 6 months, but the outcome was similar afterward. No
      neurologic deficit in any patient. In the nonoperative group, the kyphosis angle
      worsened by 4 degrees, and the retropulsion decreased from 34% to 15%. In the
      operative group, there was one case of superficial infection and two cases of
      broken screws. The kyphosis angle was improved initially by 17 degrees, but this
      was gradually lost. Hospital charges were four times higher in the operative
      group. CONCLUSIONS: Short-segment posterior fixation provides partial kyphosis
      correction and earlier pain relief, but the functional outcome at 2 years is
      similar. Early activity to the point of pain tolerance can be safely allowed.

PMID- 11337623
TI  - Identifying feigned isokinetic trunk extension effort in normal subjects: an
      efficiency study of the DEC.
AB  - STUDY DESIGN: A test-retest comparison of maximal and feigned trunk extension
      effort in normal subjects was performed. OBJECTIVE: To test the robustness of an
      index termed DEC for differentiating maximal from feigned effort in normal
      subjects. SUMMARY OF BACKGROUND DATA: Previous studies have indicated that the
      DEC, which is the difference between the eccentric to concentric strength ratio
      at two test velocities, is a powerful identifier of feigned effort. This has been
      found for various muscle groups including the trunk extensors. However, whether
      this efficiency is affected by exposure to the protocol, learning, or other
      factors had not been examined. METHODS: Using a KinCom isokinetic dynamometer, 18
      men and 17 women were tested twice within 1 to 2 weeks. Concentric and eccentric
      efforts of the trunk extensors were exerted using a short range of motion (20
      degrees ) and two test velocities (10 degrees and 40 degrees per second). In the
      first part of each test, participants exerted maximal force against the lever
      arm, whereas in the second part they were to feign their maximal capability,
      pretending the presence of injury. RESULTS: In both Tests I and II, the feigned
      DEC scores (DECf) of all the participants were greater than the maximal DEC
      (DECm) scores (P = 0.0001). Repeated measurement analysis showed that neither
      DECm nor DECf varied systematically from Test 1 to Test 2. On the basis of the
      individual male scores, the DEC cutoff score of 0.41 was 100% efficient in Test 1
      at differentiating feigned from maximal effort, with neither false-positive nor
      false-negative cases. Test 2 had a single false-positive case (efficiency 95%),
      and the optimal cutoff score was 0.275. In the female group, the corresponding
      efficiency of the DEC was 82% (optimal cutoff, 0.35) for Test 1 and 70% (optimal
      cutoff, 0.25-0.35) for Test 2. A statistical model for tolerance intervals at
      90%, 95% and 99% indicated higher cutoff values for women than men. CONCLUSION:
      In healthy subjects, the DEC effectively differentiates feigned from maximal
      performance.

PMID- 11337624
TI  - Influence of different types of progressive idiopathic scoliosis on static and
      dynamic postural control.
AB  - STUDY DESIGN: Balance control assessment of static and dynamic conditions was
      performed to study the effects of progressive idiopathic scoliosis on postural
      control in 102 adolescents. OBJECTIVE: To determine how the type and location of
      idiopathic scoliosis may affect global balance control. SUMMARY OF BACKGROUND
      DATA: Idiopathic scoliosis may impair postural control components, but the
      repercussions for global balance are relatively mild. METHODS: The following four
      different types of idiopathic scoliosis were compared: thoracic (n = 36),
      thoracolumbar (n = 22), lumbar (n = 23), and double major (n = 21) curves. Center
      of foot pressure displacements and electromyographic responses were recorded
      using static and dynamic posturographic tests (single and fast upward tilt, slow
      sinusoidal oscillations). RESULTS: The major criteria of postural control were
      better in the double major group for all the tests. In the static test, the
      patients with high major curves performed better than those with low major
      curves. In the fast dynamic test, similar latency values were observed in all the
      groups. In the slow dynamic test, better results were observed for the patients
      with low major curves. CONCLUSIONS: These data demonstrate that idiopathic
      scoliosis indeed alters balance control, with different hierarchies, from the
      best to the worst as follows: double major, thoracic, thoracolumbar, and lumbar
      curves in the static test and double major, lumbar, thoracolumbar, and thoracic
      curves in the slow dynamic test. The location of the major curve appeared to be
      important, with an effect on lateral disequilibrium and vestibular symmetry. The
      absence of anomaly in the fast dynamic test suggests that the type of scoliosis
      does not impair proprioception.

PMID- 11337625
TI  - Periradicular infiltration for sciatica: a randomized controlled trial.
AB  - STUDY DESIGN: A randomized, double-blind trial was conducted. OBJECTIVES: To test
      the efficacy of periradicular corticosteroid injection for sciatica. SUMMARY OF
      BACKGROUND DATA: The efficacy of epidural corticosteroids for sciatica is
      controversial. Periradicular infiltration is a targeted technique, but there are
      no randomized controlled trials of its efficacy. METHODS: In this study 160
      consecutive, eligible patients with sciatica who had unilateral symptoms of 1 to
      6 months duration, and who never underwent surgery were randomized for double
      blind injection with methylprednisolone bupivacaine combination or saline.
      Objective and self-reported outcome parameters and costs were recorded at
      baseline, at 2 and 4 weeks, at 3 and 6 months, and at 1 year. RESULTS: Recovery
      was better in the steroid group at 2 weeks for leg pain (P = 0.02), straight leg
      raising (P = 0.03), lumbar flexion (P = 0.05), and patient satisfaction (P =
      0.03). Back pain was significantly lower in the saline group at 3 and 6 months (P
      = 0.03 and 0.002, respectively), and leg pain at 6 months (13.5, P = 0.02). Sick
      leaves and medical costs were similar for both treatments, except for cost of
      therapy visits and drugs at 4 weeks, which were in favor of the steroid injection
      (P = 0.05 and 0.005, respectively). By 1 year, 18 patients in the steroid group
      and 15 in the saline group underwent surgery. CONCLUSIONS: Improvement during the
      follow-up period was found in both the methylprednisolone and saline groups. The
      combination of methylprednisolone and bupivacaine seems to have a short-term
      effect, but at 3 and 6 months, the steroid group seems to experience a "rebound"
      phenomenon.

PMID- 11337626
TI  - Flexion osteotomy of the cervical spine: a new technique for correction of
      iatrogenic extension deformity in ankylosing spondylitis.
AB  - STUDY DESIGN: A new surgical technique of cervical osteotomy to correct an
      extension deformity of the cervical spine is described, and a case is reported.
      OBJECTIVES: To emphasize the disparate effect of osteotomy level on sagittal
      balance and gaze angle in surgical correction of global kyphotic deformity, and
      to describe a new surgical technique. SUMMARY OF BACKGROUND DATA: Previous
      reports of cervical osteotomy essentially have described extension osteotomy for
      correction of severe flexion deformity. To the authors' knowledge, flexion
      osteotomy to correct extension deformity of the cervical spine has not been
      described previously. METHODS: A 44-year-old woman with global kyphotic deformity
      caused by ankylosing spondylitis underwent corrective lumbar osteotomy at another
      institution. Ten years later, she experienced further development of the
      kyphosis, predominantly at the thoracic level, with resultant restriction of
      forward gaze. Thoracic corrective osteotomy was performed, which resulted in an
      upward deviation of her visual field. A flexion osteotomy was performed at C7-T1,
      using two separate posterior and anterior approaches, in one-stage, in the
      lateral decubitus. The use of transparent drapes permitted direct visualization
      of the chin-brow angle during operation. Anterior plate fixation prevented any
      translation at the osteotomy site. RESULTS: The osteotomy united; the gaze angle
      was fully corrected (45 degrees to -30 degrees ). No deterioration was noted at 2
      year follow-up. CONCLUSIONS: Osteotomy at a higher level in the spine for
      correction of global kyphotic deformity may result in a significant
      overcorrection of the gaze angle upward. The authors believe that the new
      technique described in this report is a technically demanding but adequate and
      safe approach for correcting such a rare deformity.

PMID- 11337627
TI  - Early retropulsion of titanium-threaded cages after posterior lumbar interbody
      fusion: a report of two cases.
AB  - STUDY DESIGN: Two patients had postoperative posterior migration of titanium
      fusion cages after posterior lumbar interbody fusion. They underwent a repeat
      posterior procedure and posterior fusion with pedicle screws. OBJECTIVE: To
      suggest a treatment for posterior migration of titanium-threaded cages causing
      spinal stenosis after posterior lumbar interbody fusion. SUMMARY OF BACKGROUND
      DATA: The use of titanium fusion cages in posterior lumbar interbody fusion is
      gaining popularity as a technique for arthrodesis. The literature contains only a
      few reports concerning complications associated with their use. METHODS: Two
      patients had retropulsion of titanium threaded cages, ten days and 2 months after
      posterior lumbar interbody fusion. The retropulsed cages compressing the dura,
      caused sudden onset of back pain and radiating pain to the lower extremities.
      Both patients underwent repeat posterior procedure that included repositioning of
      the cages and posterior fusion with pedicle screws. RESULTS: Symptoms of back and
      leg pain subsided after repositioning of the cages and application of the pedicle
      screws. CONCLUSIONS: A repeat posterior approach and repositioning of the
      retropulsed titanium fusion cages in addition to posterior fusion with pedicle
      screws successfully managed this complication.

PMID- 11337628
TI  - The use of traction methods to correct severe cervical deformity in rheumatoid
      arthritis patients: a report of five cases.
AB  - STUDY DESIGN: A case series is presented. OBJECTIVES: To describe the methods of
      correction used in this study for flexible severe cervical deformity, and to
      report the results in patients with rheumatoid arthritis. SUMMARY OF BACKGROUND
      DATA: Long-standing rheumatoid arthritis can lead to severe cervical deformity,
      causing significant functional deficits and poor cosmesis. Information on the use
      of traction combined with surgical stabilization to achieve correction of
      flexible deformity in rheumatoid patients is sparse in the English literature.
      METHODS: A review of five cases, including pertinent history, physical
      examination, radiographic evaluation, traction techniques, surgical
      stabilization, and outcomes, was conducted. RESULTS: Excellent correction of
      deformity and radiographic union were achieved in all the patients. One patient
      had minimal loss of correction after surgery and thereafter remained stable. Pin
      tract infections were the only significant complication. CONCLUSIONS: Severe
      cervical flexible deformity in rheumatoid patients can cause significant
      disability and can be treated successfully with a combination of traction
      techniques and surgical stabilization.

PMID- 11337629
TI  - Osteochondroma of the thoracic spine and scoliosis.
AB  - STUDY DESIGN: The case of a 16-year-old patient with an osteochondroma in T11 and
      scoliosis is reported. OBJECTIVE: To describe the treatment of an osteochondroma
      with scoliotic deformity and the imaging methods used for the diagnosis. SUMMARY
      OF BACKGROUND DATA: Osteochondromas arising in the vertebral column are rare.
      However, spinal involvement is found with some regularity because osteochondromas
      are among the most common benign tumors of bone. METHODS: The clinical history,
      plain radiographs, computed tomography, and magnetic resonance imaging, and
      pathologic findings of the reported patient were reviewed. The medical literature
      also was reviewed. RESULTS: The patient was treated with surgery in an attempt to
      remove the tumor and correct the aesthetic deformity. The results were
      satisfactory, with an improvement of the thoracolumbar scoliosis from 45 degrees
      to 18 degrees. CONCLUSIONS: Osteochondromas of the vertebral column may cause
      scoliosis. Computed tomography and magnetic resonance imaging are necessary for
      evaluating the origin, size, and characteristics of the tumor. In this case,
      surgical management involved resection of the tumor and correction of the
      scoliotic deformity.

PMID- 11337630
TI  - Transient paraparesis: a complication of the surgical management of Scheuermann's
      kyphosis secondary to thoracic stenosis.
AB  - STUDY DESIGN: Transient paraparesis during the operative management of a 16-year
      old patient with Scheuermann's kyphosis secondary to thoracic stenosis is
      reported. OBJECTIVE: To describe a treatable cause for paraparesis in a patient
      with Scheuermann's kyphosis undergoing surgical treatment. SUMMARY OF BACKGROUND
      DATA: Cord injury in the surgical treatment of Scheuermann's kyphosis is a rare
      event, yet it is felt to be more common in the surgical correction of kyphosis
      than in surgery for scoliosis. Suggested etiologies have included vascular
      insufficiency, hypotension, direct mechanical trauma, and neural element stretch.
      Concomitant thoracic spinal stenosis predisposing to neurologic injury during
      surgical manipulation has not been reported. METHODS: A 16-year-old boy with
      progressive Scheuermann's kyphosis measuring 80 degrees from T7 to T12 underwent
      an anteroposterior spinal fusion with somatosensory-evoked potential monitoring
      and wake-up tests. During the instrumentation posteriorly, somatosensory-evoked
      potential monitoring became markedly abnormal. This was followed by a wake-up
      test that demonstrated the patient's inability to move either of his lower
      extremities. All instrumentation was removed. The patient had recovered
      neurologic function by the time he reached the recovery room. A computed
      tomography myelogram was performed on the third postoperative day, which
      demonstrated severe thoracic stenosis from T8 to T10. The patient was returned to
      the operating room 1 week later to undergo a posterior laminectomy from T7 to T11
      and instrumented fusion from T5 to L2. Somatosensory-evoked potential monitoring
      was stable throughout this procedure, and the wake-up test was normal. RESULTS:
      The patient's postoperative course and subsequent 2-year follow-up period were
      unremarkable. He progressed to clinical and radiographic union and maintained a
      normal lower extremity neurologic examination. CONCLUSIONS: A treatable cause for
      paraparesis secondary to the surgical treatment of Scheuermann's kyphosis is
      presented. The author currently obtains a thoracic magnetic resonance image (MRI)
      before the surgical correction of any patients with Scheuermann's kyphosis.

PMID- 11337631
TI  - Idiopathic spinal cord herniation associated with intervertebral disc extrusion:
      a case report and review of the literature.
AB  - STUDY DESIGN: A case of idiopathic spinal cord herniation is reported, and the
      literature is reviewed. OBJECTIVE: To report a case of thoracic spinal cord
      herniation with a ventral dural defect, probably caused by thoracic disc
      extrusion. SUMMARY OF BACKGROUND DATA: Recently, reports of spinal cord
      herniation have been increasing. This increase can be attributed to the
      development of magnetic resonance imaging and increased awareness of this entity.
      However, the cause of the ventral dural defect remains unknown. METHODS: A 54
      year-old woman had experienced Brown-Sequard syndrome for 2 years. Magnetic
      resonance imaging demonstrated an S-shaped anterior kinking of the spinal cord,
      with dilation of the dorsal subarachnoid space. RESULTS: After incision of the
      dural sac and gentle retraction of the spinal cord, a dural defect was recognized
      into which the spinal cord had herniated. An extruded disc was visualized through
      the defect at T3-T4. The ventral dural defect and the dorsal incision of the
      dural sac were repaired with a fascial graft from the thigh. CONCLUSIONS:
      Intraoperative findings suggest that the thoracic disc herniation in the current
      case was the probable cause of the ventral dural defect. Surgical reconstruction
      using double fascial graft under careful spinal cord monitoring resulted in a
      satisfactory neurologic recovery.

PMID- 11337632
TI  - Anterior versus posterior instrumentation for the correction of thoracic
      idiopathic scoliosis.
AB  - Traditionally, thoracic idiopathic scoliosis has been treated by posterior
      instrumentation and fusion, which is still the gold standard. However, anterior
      instrumentation and fusion became a viable option for these patients during the
      1990s and are gaining acceptance. Currently, controversy still exists regarding
      the indications for the anterior approach, and the benefits of the anterior
      versus posterior approach remain unsettled. Therefore, this topic was considered
      ideal for noted experts on both sides to present their opinions, with Dr. Harry
      Shufflebarger promoting posterior instrumentation and Dr. Randy Betz encouraging
      anterior instrumentation. The efforts of these two outstanding and dedicated
      scoliosis specialists to educate the readers of Spine regarding their viewpoints
      are appreciated.

PMID- 11337634
TI  - Intradiscal solid phase displacement as a determinant of the centripetal fluid
      shift in the loaded intervertebral disc.
AB  - STUDY DESIGN: The movement of cross sections of the monofilament nylon threads
      inserted into the axially loaded intervertebral disc was traced with magnetic
      resonance imaging (MRI). This technique allowed the observation of the sequential
      solid phase displacement of the loaded intervertebral disc. OBJECTIVES: To
      clarify sequential solid phase displacement of the axially loaded intervertebral
      disc to elucidate the cause of centripetal fluid shift within a disc. SUMMARY OF
      BACKGROUND DATA: We already have reported that there is a centripetal fluid shift
      within the axially loaded intervertebral disc during the early phase of loading.
      We assumed that there should be an elaborate intradiscal matrix displacement that
      generates a pressure gradient within the disc to cause a centripetal fluid shift.
      METHODS: Thirteen freshly obtained bovine caudal intervertebral discs were
      prepared. Three to five monofilament nylon threads were inserted into each disc
      in the anterior-posterior direction to trace the intradiscal solid phase
      displacement on the midcoronal MR images. Sequential displacement of the disc
      matrix was recorded during a 294 N axial loading. RESULTS: Relatively large
      centrifugal expansion at the inner layer of the anulus fibrosus compared with
      less centrifugal expansion of the outer anulus fibrosus was observed in accord
      with gradual creep of the disc thickness. CONCLUSIONS: The uneven displacement of
      the intradiscal solid phase observed in the present study expels the fluid phase
      from the inner anulus fibrosus, thus resulting in accumulation of fluid phase in
      the nucleus pulposus. The present study suggests the presence of a mechanism that
      retains water within the normal intervertebral disc, in spite of an external
      load, because it forms a water-abundant nucleus pulposus, which is surrounded by
      an anulus fibrosus with decreased water permeability caused by fluid loss. A more
      detailed analysis is required to clarify topographic volumetric changes within
      the disc.

PMID- 11337635
TI  - Complications and results of long adult deformity fusions down to l4, l5, and the
      sacrum.
AB  - STUDY DESIGN: This is a consecutive study of patients having undergone surgical
      treatment of adult lumbar scoliosis. Follow-up ranged from 2 to 13 years (average
      5 years). OBJECTIVES: To assess the complications and outcomes of patients with
      long fusions to L4 (n=23), L5 (n=21), or the sacrum (n=15) and determine if a
      "deeply seated" L5 segment is protective. SUMMARY OF BACKGROUND DATA: Few studies
      assess outcomes and complications in adults fused from the thoracic spine to L4,
      L5, or the sacrum with minimum 2-year follow-up. METHODS: Fifty-eight patients
      (59 cases; average age 43 years; range 21 to 60) with minimum 2-year follow-up
      were analyzed for subsequent spinal degeneration and complications. Outcomes were
      assessed from questionnaires administered at latest follow-up. RESULTS: Sixteen
      percent of cases (7 of 44) fused short of the sacrum displayed subsequent
      postoperative distal spinal degeneration, although only three patients were
      symptomatic. Compared with the group with no subsequent degeneration, this group
      had a lower improvement in function and pain relief. Other complications for
      patients fused short of the sacrum included two cases with crosslink breakage,
      one with neurologic deficit, three with pseudarthroses, one with hook pullout,
      and one with L5 screw pullout. For cases fused to the sacrum, two cases with deep
      wound infections and one with loose iliac screw requiring removal were observed.
      Because two of four cases fused to L5 with subsequent degeneration at L5-S1 were
      observed to have "deeply seated" L5 segments and two of the four did not, the
      authors could conclude only that "deep seating" of L5 is not absolute protection.
      CONCLUSIONS: Fusions short of the sacrum did not have predictable long-term
      results. Those fused short of the sacrum who developed distal spinal degeneration
      had worse outcomes. Patients fused to the sacrum did not have a higher
      complication rate. A "deeply seated" L5 segment does not necessarily protect the
      L5-S1 disc.

PMID- 11337636
TI  - Zenker's diverticulum associated with multilevel cervical osteomyelitis.
AB  - STUDY DESIGN: A case report of cervical osteomyelitis possibly associated with a
      Zenker's diverticulum perforation. OBJECTIVES: To present clinical, radiologic,
      and surgical findings of a cervical osteomyelitis due to a Zenker's diverticulum
      perforation. SUMMARY OF BACKGROUND DATA: A 56-year-old patient was in an
      intensive care unit for a severe head injury. He was fed via a nasogastric tube.
      Four months later he developed a pyogenic cervical vertebral infection. METHODS:
      Plain films and magnetic resonance imaging showed a diffuse cervical
      osteomyelitis. Investigation of his dysphagia revealed a Zenker's diverticulum.
      RESULTS: After administration of antibiotics and surgical treatment of the
      diverticulum, the cervical infection resolved. Plain films and magnetic resonance
      imaging showed healing with vertebral fusion. CONCLUSIONS: Cervical osteomyelitis
      is uncommon. Only one case of direct contamination leading to cervical vertebral
      osteomyelitis after esophageal perforation has been previously described. Direct
      contamination of the prevertebral soft tissues by bacteria traveling through the
      fistula may have occurred. The development of vertebral osteomyelitis in this
      case is consistent with the hypothesis of direct contamination. Management relies
      on appropriate antimicrobial therapy and surgical management of the diverticulum.
      The association of Zenker's diverticulum with vertebral osteomyelitis and
      discitis is a unique, previously undescribed situation.

PMID- 11337638
TI  - [Foundation of the National Authority for Continuing Education in Anesthesia and
      Resuscitation (ACC-ECM)].

PMID- 11337639
TI  - [Sedation in intensive care].

PMID- 11337640
TI  - Options on the use of muscle relaxants in clinical anaesthesia.

PMID- 11337641
TI  - Use of sedative and analgesic drugs in the first week of ICU stay. A pharmaco
      epidemiological perspective.
AB  - AIM: To assess the current practice of pharmacological sedation and analgesia in
      patients admitted in Italian intensive care units. METHODS:  DESIGN:
      observational, prospective, cohort study, involving all patients admitted during
      a one-month period to participating Centers in 1994. All patients were followed
      up for vital status until discharge and evaluated for pharmacological sedation
      and analgesia for the first week of ICU stay. SETTING: 128 Italian, adult,
      general, intensive care units, approximately representing 1/3 of all Italian
      Units. PATIENTS: 2932 patients were analyzed. They generated 22612 patient-days
      of intensive care unit stay, 11221 of which were evaluated. RESULTS: A total of
      31 different sedative drugs were used in 1751 patients. On 64% of sedated days
      only one drug was utilized, whereas two or more drugs were administered in the
      remaining days. Propofol was the most widely prescribed drug, followed by
      fentanyl and diazepam, while morphine accounted for 14.8% of sedated days. The
      analysis of the pattern of sedation over time revealed a trend to linearly reduce
      the use of this practice. CONCLUSIONS: Our results depict a relatively low
      prevalence of sedation in Italy, with the use of large number of different
      agents. We also observed a larger than expected use of some drugs, like propofol
      and fentanyl, that could be due to the unavailability of new sedative and
      analgesic drugs in Italy on 1994. In conclusion, Italian intensivists seem to be
      very conservative about the practice of pharmacological sedation in critically
      ill patients.

PMID- 11337642
TI  - Non-invasive pressure support ventilation in acute hypoxemic (non hypercapnic)
      respiratory failure. Observations in Respiratory Intermediate Intensive Care
      Unit.
AB  - BACKGROUND: Non-invasive positive pressure support ventilation (NIPSV). METHODS:
      In patients with acute hypoxaemic (PaO2/FiO2 &Mac178;100) non hypercapnic
      respiratory failure (ARF) admitted to a Respiratory Inter-mediate Intensive Care
      Unit of a general Hospital, between January 1993 and December 1997. RESULTS: In
      21 selected patients (PaO2/ FiO2T0=82+/-9) NIPSV improved PaO2 in 13/21 patients
      (Group A) and did not improve in 8/21 patients (Group B) (PaO2/FiO2T1=154+/-25 in
      Group A vs PaO2/FiO2T1=106+/-7.5 in Group B, p=0.00001). Upon admission the two
      groups did neither significantly differ for blood gas values (PaO2/FiO2T0=84+/
      9.6 in Group A vs 79.8+/-8.7 in Group B), nor for clinical status (APACHE
      II=19.8+/-5 in Group A vs 24.6+/-7 in Group B). Shorter duration of NIPSV in
      Group B patients (11.2+/-19.7 hrs vs 35.3+/-32.3 hrs in Group A, p=0.047), in
      spite of a rise in PEEP (9.3+/-2.3 in Group B vs 5.5+/-2.4 in Group A, p=0.003)
      and Pressure Support (18.7+/-1.8 in Group B vs 15+/-3.2 in Group A, p=0.004) was
      due to onset of conditions which required shifting from NIPSV to endotracheal
      intubation (ETI). OUTCOME: 8/21 patients were successfully treated by only NIPSV.
      8/21 patients were intubated. 5/21 patients dead in RIICU; 1 month survival: 9/21
      patients. Side effects: mask intolerance (3/21); skin necrosis (1/21);
      pneumothorax (1/21). CONCLUSIONS: NIPSV may be tried in ARF patients to improve
      PaO2 and avoid ETI.

PMID- 11337644
TI  - Application of the self-inflating bulb to a hollow intubating introducer.
AB  - BACKGROUND: The aspiration test, performed by a self-inflating bulb (SIB), is a
      simple and reliable method to detect an accidental esophageal intubation. The aim
      of the study, in case of employment of a hollow intubating introducer (HII), was
      to verify the possibility to directly perform the test with the introducer and
      its efficacy in allowing the detection of its position. METHODS:  EXPERIMENTAL
      DESIGN: prospective, randomized study. ENVIRONMENT: operating theater in a
      university hospital. PATIENTS: adult patients, without evidence of gastro
      esophageal or tracheobronchial pathologies, scheduled for elective surgery.
      INTERVENTIONS: patients were randomized in two groups T (HII was placed in
      trachea) and E (HII was positioned in the esophagus). Under general anesthesia, a
      HII was placed in either the trachea or the esophagus. A blinded anesthesiologist
      connected the SIB to the HII and performed the test twice. MEASUREMENTS: the
      anesthesiologist inferred the position of the device, based on the re-inflation
      observed. RESULTS: One hundred subjects were studied. In group E patients, a
      prompt and complete re-inflation of the bulb was never observed and the
      anesthesiologist correctly inferred the position of the HII. Occasionally (3.5%
      of cases), in group T patients, a prevented or incomplete re-inflation of the
      bulb occurred, leading to an incorrect judgment of the HII position. CONCLUSIONS:
      The aspiration test with the SIB allows the proper detection of the introducer in
      esophagus. When used in combination with a HII, both time and local trauma
      associated with an erroneous, introducer-guided esophageal intubation in case of
      difficult laryngoscopy may be reduced.

PMID- 11337643
TI  - [Thoracic epidural analgesia (TEA) in clinical practice: effects, technique,
      complications and suggestions during anticoagulant treatment].
AB  - The effects of thoracic peridural analgesia (TEA) on the neuroendocrine response
      to surgery are well known, but, at the present this technique is not widely used
      especially in Italy. The aim of this paper is to give information and suggestions
      on thoracic epidural analgesia in thoracic and cardiac surgery, and to discuss
      how anticoagulant therapy may interfere on this technique.

PMID- 11337645
TI  - [Alterations in left ventricular-arterial coupling and mechanical efficiency
      produced by remifentanil during cardiac anesthesia].
AB  - BACKGROUND: The performance of the cardiovascular system depends on the
      interaction of the left ventricle and arterial system. An appropriate coupling of
      these two components is important to quantify the efficiency of myocardium,
      determined by Ea/Ees. The end-systolic elastance of the left ventricle (Ees) is
      an index of contractility which is independent of loading conditions, while the
      arterial end-systolic elastance (Ea) represents the properties of the arterial
      system. The aim of our study is to investigate the effects of a bolus of
      remifentanil (R) on myocardial efficiency. METHODS: In a period of 3 months we
      examined prospectively the effects of R in a group of 12 patients, ASA IV, 49-75
      years old, submitted intraoperatively to cardiac anesthesia for revascularization
      of myocardium. After induction of anesthesia and before the beginning of surgery,
      a bolus of R (1 mg/kg/min) was administered and with the use of trans-esophageal
      echocardiography we determined both the left ventricle end-systolic volume and
      end-diastolic volume to assess, with different end-systolic arterial pressures,
      the ventricle elastance (Ees) and arterial elastance (Ea) before and after
      administration of R. RESULTS: The present findings indicate that R decreases the
      ventricular elastance from 6.07 mmHg/ml/m2 to 4.8, with a less decrease of
      arterial elastance from 3.69 mmHg/ml/m2 to 3.07. CONCLUSIONS: The results suggest
      that R preserves a good left ventricular-arterial coupling and mechanical
      efficiency, despite a little increase of coupling, probably because ventricular
      and arterial properties are so matched as to minimize the systolic work of the
      left ventricle.

PMID- 11337646
TI  - Abdominal aortic aneurysm resection following cholecystectomy and heart
      transplantation. Case report.
AB  - The case of a patient who underwent heart transplantation and cholecystectomy in
      1993 and admitted for resection of abdominal aortic aneurysm in May 1997, is
      reported. About 25 minutes after unclamping the abdominal aorta the patient s
      blood pressure fell suddenly to 70/40 mmHg. In spite of vigorous fluid
      administration and infusion of Dopamine and Adrenaline the hemodynamic pattern
      returned to normal only 15 minutes later. The authors discuss the possible
      explanations of this behaviour (mesenteric traction syndrome, hypovolemia) and
      conclude that heart transplant patients are particularly affected by hypotension.
      Of paramount importance remains therefore the correct evaluation of adequate
      filling pressures which should be maintained slightly above normal range.

PMID- 11337647
TI  - [About "informed consent"].

PMID- 11337648
TI  - [Recommendations on perioperative normothermia. Working Group on Perioperative
      Hypothermia, Italian Society for Anesthesia, Analgesia, Resuscitation, and
      Intensive Care].

PMID- 11337649
TI  - Portal venous ultraviolet B-irradiated donor alloantigen prevents rejection in
      circumferential rat tracheal allografts.
AB  - BACKGROUND: Before tracheal transplantation can be considered as a method of
      reconstruction in patients with extensive circumferential tracheal defects, we
      must achieve a state of nontoxic, donor-specific tolerance so that the risks of
      such a transplant do not outweigh the benefits. OBJECTIVE: Our objective was to
      determine whether a single intraportal injection of modified donor alloantigen
      achieves donor-specific immunosuppression for major histocompatibility complex
      mismatched rat tracheal allografts. STUDY DESIGN: Buffalo (recipient) rats were
      pretreated with either a single portal-vein administration of ultraviolet B (UVB)
      irradiated donor splenocytes (n = 4) or an intraportal inoculation of
      nonirradiated donor splenocytes (n = 4). Major histocompatibility complex
      mismatched Lewis (donor) tracheal allograft segments were then grafted into
      treatment groups 7 days after donor-cell pretreatment. Tracheal rejection was
      assessed by histologic analysis, mucosal cilia motility, and in vitro immunologic
      assessment. RESULTS: The UVB-treated group demonstrated no acute or chronic
      rejection as well as complete functional recovery. In vitro immunologic
      assessment demonstrated a donor-specific hyporesponsiveness and donor
      allospecificity. Untreated animals and those receiving nonirradiated donor
      splenocytes showed acute rejection of their tracheal allografts. CONCLUSION:
      Recipient pretreatment with intraportally administered UVB-irradiated donor
      splenocytes prevents rejection of circumferential rat tracheal allograft segments
      by inducing a donor-specific immune hyporesponsiveness.

PMID- 11337650
TI  - Practice patterns versus practice guidelines in pediatric otitis media.
AB  - OBJECTIVE: To study the practice patterns of physicians and their adherence to an
      evidence-based practice guideline (PG) on pediatric otitis media with effusion.
      We hypothesized that overall knowledge of the recommendations from the guidelines
      would be less than 75%, and that specialist physicians would have better
      knowledge of the recommendations than generalist physicians. METHODS: We
      performed a survey study of 1167 otolaryngologists, pediatricians, and pediatric
      otolaryngologists. Each physician was sent a 6-item survey asking about their
      practice patterns and treatment preferences for young children with otitis media
      with effusion. We compared responses between different specialties. RESULTS: The
      overall response rate was 48%. Only 8 (1.4%) of the 558 responding physicians
      answered all 6 items congruent with the PG. Overall, pediatricians,
      otolaryngologists, and pediatric otolaryngologists had similar total scores, but
      different scores on individual items. CONCLUSIONS: These results indicate that
      the practice patterns of pediatricians, otolaryngologists, and pediatric
      otolaryngologists differ from the recommendations of an evidence-based PG. In
      particular, 2 items covering key treatment recommendations were answered in
      agreement with the PG by fewer than half of the physicians. It is not clear from
      this study whether these discrepancies were due to poor dissemination or
      knowledge concerning the PG, or disagreement with its recommendations.

PMID- 11337651
TI  - Accuracy of terminology and methodology in economic analyses in otolaryngology.
AB  - OBJECTIVE: Economic studies increasingly guide health care resource allocation
      decisions. Because rigorous adherence to accepted definitions and research
      techniques is critical to ensure accuracy, we evaluated the terminology and
      methods of otolaryngology economic analyses. STUDY DESIGN: A total of 71 articles
      published from 1990 to 1999 in 6 peer-reviewed otolaryngology journals with terms
      such as "cost-effective" in their title or representing economic analyses were
      reviewed for terminology and use of established methodology guidelines. RESULTS:
      Over half (35 of 66) of terms such as "cost-effective" were used incorrectly, and
      60% of articles (39 of 64) confused "charge" and "cost" data. Eleven percent (7
      of 64) of papers specified the perspective of their analysis. About half (17 of
      30) reported a summary measure such as a cost-effectiveness ratio. Only one third
      (23 of 63) performed sensitivity analyses. CONCLUSION: Adherence to accepted
      definitions and research methods is inconsistent, although we did note moderate
      improvements in making the distinction between costs and charges, defining of
      study perspective, and performing sensitivity analysis. SIGNIFICANCE: Greater
      attention to both terminology and methodology can enhance the quality of economic
      analyses and ultimately improve certain resource allocation decisions.

PMID- 11337652
TI  - Injection snoreplasty: how to treat snoring without all the pain and expense.
AB  - OBJECTIVE: We introduce Injection Snoreplasty: an innovative, safe, and effective
      palatal snoring procedure with minimal cost and discomfort to the patient. A well
      described sclerotherapy agent, Sotradecol, is injected into the soft palate to
      reduce/eliminate palatal flutter snoring. STUDY DESIGN AND SETTING: Twenty-seven
      patients with a diagnosis of palatal flutter snoring (respiratory disturbance
      index less than 10) by sleep study were enrolled in the protocol. Office
      treatment sessions were performed 6 to 8 weeks apart. Success was judged by
      subjective improvement in snoring and objective evidence of palatal
      stiffening/scarring. RESULTS: Twenty-five (92%) of 27 patients reported
      significant decrease in snoring. There were no significant postinjection
      complications. Visual analog pain scale confirmed minimal discomfort. Most
      patients received more than 1 treatment (average, 1.8) in order to receive
      optimal palatal stiffening. CONCLUSION/SIGNIFICANCE: Injection Snoreplasty is a
      simple, safe, and effective office treatment for primary snoring. Advantages over
      current snoring procedures include simplicity, low cost, decreased posttreatment
      pain levels, and minimal/no convalescence.

PMID- 11337653
TI  - Cerebrospinal fluid fistula after transtemporal skull base surgery.
AB  - OBJECTIVES: The purpose of this article is to outline our methods for the
      prevention and management of cerebrospinal fluid (CSF) leak after transtemporal
      skull base surgery. METHODS: A total of 589 patients underwent a variety of
      transtemporal surgical approaches for the extirpation of skull base tumors at our
      institution from July 1988 to October 1999. The medical records were
      retrospectively reviewed to identify the tumor histology, size, and location as
      well as the surgical approach, defect reconstruction technique, and the incidence
      of postoperative CSF leak. RESULTS: The risk of CSF fistulae was greatest in
      utilizing the restrosigmoid approach (8%) and least in those who underwent a
      translabyrinthine approach (4%). Tumor size had no bearing on the incidence of
      the CSF leak and the overall incidence of meningitis was 1.0%. CONCLUSION: The
      proper surgical technique will minimize the risk of CSF leak after transtemporal
      skull base surgery. Immediate management of CSF fistulae helped prevent
      meningitis in the majority of these patients.

PMID- 11337654
TI  - Ventral approach to the rat middle ear for otologic research.
AB  - OBJECTIVE: To describe a simple approach to the rat middle ear because there are
      few clear descriptions of this technique with minimal morbidity and mortality.
      STUDY DESIGN AND SETTING: Six male Long-Evans rats were used in this study. We
      designed a cervical approach to the middle ear with the purpose of creating an
      experimental model of ossiculoplasty that permits the postoperative survival of
      the animal. RESULTS: It was possible in all cases to visualize the majority of
      structures of the tympanic cavity: promontory, round window, stapedial artery,
      stapes, incus, and tympanic membrane. There were no cases of postoperative
      infection or facial paralysis. CONCLUSIONS AND SIGNIFICANCE: The ventral approach
      to the rat middle ear is a rapid and simple technique that makes the rat the
      animal of choice for many otologic investigations.

PMID- 11337655
TI  - Revision myringoplasty with solvent-dehydrated human dura mater (Tutoplast).
AB  - OBJECTIVES: Several grafting materials have been used in the reconstruction of
      the perforations of the tympanic membrane. The use of dehydrated dura homografts
      as a substitute for the tympanic membrane has not been fully documented. On the
      other hand, revision surgery is more critical in terms of patients' expectations.
      The aim of this study is to determine the tissue stiffness, the compliance, and
      the wound healing rate of dura homografts in revision surgery of perforations of
      the tympanic membrane. STUDY DESIGN AND SETTING: The charts of 45 patients who
      have received dura grafts because of re-perforation or failure of the
      myringoplasty have been reviewed retrospectively. The healing process of the
      myringoplasty, graft take rate, pure-tone hearing level, and tympanogram were
      reviewed. RESULTS AND CONCLUSION: It has been concluded that dura homografts,
      which have excellent tissue-compatibility, stability, and an 86.7% graft success
      rate, are preferred in patients in whom their own temporalis fascia cannot be
      used because of previous operations. It has been demonstrated by tympanometric
      analysis that the compliance of the graft during various pressure applications is
      as good as the normal eardrum.

PMID- 11337656
TI  - Hearing loss in progressive systemic sclerosis patients: a comparative study.
AB  - OBJECTIVE: To investigate the middle and inner ear involvement in patients with
      progressive systemic sclerosis (PSS). STUDY DESIGN AND SETTINGS: We prospectively
      evaluated 34 PSS 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 45 age-matched healthy
      subjects. RESULTS: We found a sensorineural hearing loss in 20% and mixed type
      hearing loss in 3.3% of the patients. There was no correlation of hearing loss
      with age, systemic manifestations of the disease, presence of autoantibodies, and
      drug therapy. Ten percent of the patients had patulous eustachian tubes.
      CONCLUSION: One fourth of PSS patients had a hearing loss affecting the middle
      and mainly the high frequencies. This is a lower percentage than that reported by
      other investigators. A significant prevalence of bilateral patulous eustachian
      tubes was noticed as well. Further investigation is needed for a better
      understanding of the mechanism of ear damage in PSS patients.

PMID- 11337657
TI  - Short-lasting drop attacks in Meniere's disease.
AB  - OBJECTIVES: To study the vertigo attacks known as Tumarkin attacks or drop
      attacks (DA). DA are characterized by sudden loss of balance with or without
      falls but with preserved consciousness, and they are supposedly triggered by
      changes in the otolith function of Meniere's disease (MD). STUDY DESIGN AND
      SETTING: Data from 243 consecutive MD patients were collected into a database of
      an otoneurologic expert system. RESULTS: DA was experienced by 72% (n = 173) of
      the patients with MD. It correlated with visually provoked vertigo. Gait
      difficulties, tinnitus, and anxiety were more common in the DA group. Long
      lasting vertigo attacks were more frequently provoked in the DA subjects by
      physical strain (58% vs 14%), head movements or changes in head position (71% vs
      48%), pressure changes (54% vs 12%), or rapid movements in visual surroundings
      (65% vs 35%) than in the non-DA subjects. CONCLUSION: DA are common in MD
      patients. The abrupt occurrence of DA make them poorly tolerated. SIGNIFICANCE:
      DA are more common in advanced MD.

PMID- 11337658
TI  - Diagnostic accuracy of fine-needle aspiration and frozen section in nodular
      thyroid disease.
AB  - OBJECTIVE: To assess the diagnostic accuracy of fine-needle aspiration (FNA) and
      frozen section (FS) in nodular thyroid disease. SETTING: Tertiary care academic
      medical center. STUDY DESIGN: Retrospective review of 139 consecutive patients
      undergoing surgery for nodular thyroid disease. FNA and FS sensitivity,
      specificity, and accuracy were calculated with respect to permanent section
      histology. RESULTS: Among 63 patients with an FNA interpreted as either benign (n
      = 38) or malignant (n = 25), FNA was accurate (sensitivity 89%, specificity 97%,
      accuracy 94%). FS identified only one case of carcinoma missed by FNA. Among 76
      patients with a "suspicious" FNA, FS was reasonably accurate (sensitivity 67%,
      specificity 100%, accuracy 89%), but was deferred in 50% of cases. CONCLUSION:
      Given high FNA accuracy, more selective use of FS is suggested. SIGNIFICANCE: The
      study results will assist with intra-institutional patient counseling and
      intraoperative decision-making with respect to FNA and FS results in patients
      with nodular thyroid disease.

PMID- 11337659
TI  - Prospective analysis of the efficacy of continuous intraoperative nerve
      monitoring during thyroidectomy, parathyroidectomy, and parotidectomy.
AB  - OBJECTIVE: Continuous intraoperative electromyographic monitoring was
      prospectively performed in all parotidectomies, thyroidectomies, and
      parathyroidectomies over approximately 5 years to assess the efficacy of this
      technology. STUDY DESIGN AND SETTING: Continuous intraoperative nerve monitoring
      with perioperative nerve assessment was performed. The postresection minimal
      stimulation level of the nerves was determined to evaluate if this level would
      predict nerve function postoperatively. RESULTS: Forty-four parotidectomies and
      70 thyroid/parathyroid operations were performed with 140 nerves at risk (44
      facial, 96 recurrent laryngeal). The incidence of temporary facial paralysis was
      15.9% (7 of 44) and the incidence of permanent paralysis was 0%. The incidence of
      temporary recurrent laryngeal nerve paralysis in terms of nerves at risk was 1.0%
      (1 of 96), and the incidence of permanent recurrent laryngeal nerve paralysis was
      0%. All patients with normally functioning facial and recurrent laryngeal nerves
      postoperatively had minimal stimulation levels less than or equal to 0.4 mA.
      CONCLUSION: Continuous intraoperative nerve monitoring was associated with
      extremely low rates of temporary and permanent nerve paralysis in our series of
      140 nerves at risk as compared to the rates documented in the literature.

PMID- 11337660
TI  - Value of flow cytometry in the evaluation of head and neck fine-needle lymphoid
      aspirates: a 3-year retrospective review of a community-based practice.
AB  - OBJECTIVE: To study the clinical efficacy of flow cytometry in patients suspected
      of having a lymphoma with head and neck pathology. STUDY DESIGN: Retrospective
      review of 49 patients with lymphoid aspirates having concurrent flow cytometry
      studies. SETTING: Private practice office-based study. CONCLUSION: Fine-needle
      aspiration with concurrent flow cytometry is a useful, convenient adjunct to the
      diagnosis of head and neck non-Hodgkins lymphomas. SIGNIFICANCE: Flow cytometry
      is a significant improvement over fine-needle aspiration derived cytologic
      diagnosis alone. Tissue open biopsy may be avoided altogether in some patients
      with non-Hodgkins lymphoma.

PMID- 11337661
TI  - Versatility and donor site morbidity of the lateral upper arm flap in intraoral
      reconstruction.
AB  - OBJECTIVE: The lateral upper arm flap is not widely used yet for intraoral defect
      reconstruction. Investigation of its morphologic and functional outcome was the
      objective of this study. STUDY DESIGN: The morphologic and functional results of
      recipient (swallowing, flap survival, dehiscence of margins, cutaneous fistulas,
      intraoral hairs) and donor sites (wound healing, scar width and length, sensory
      and motor disturbance) (n = 44) were checked clinically. Postoperative swallowing
      was investigated via videofluorography (n = 11). RESULTS: The lateral upper arm
      flap showed low donor site morbidity, primary closure was achieved in all but one
      case. Sensory deficit at the proximal forearm (n = 27) occurred without any case
      of compromise of radial nerve function. Videofluorography allows for objective
      evaluation of swallowing function. CONCLUSIONS: The lateral upper arm flap is the
      reconstruction of first choice for intraoral defects due to its low donor site
      morbidity.

PMID- 11337662
TI  - T3 glottic cancer: oncologic results and prognostic factors.
AB  - OBJECTIVES: To analyze oncologic results, prognostic factors, and consideration
      of transglottic tumors as a separate entity in 73 patients with T3 glottic
      carcinoma treated by surgery +/- radiation therapy at La Paz University Hospital
      from 1984 to 1994. METHODS: Sixty-four patients underwent a total laryngectomy;
      neck dissection was performed in 50 patients; 29 patients received postoperative
      radiotherapy. RESULTS: The 5-year overall survival, cause-specific survival, and
      relapse-free survival rates were 58.1%, 66.8%, and 63.7%. Univariate analysis
      revealed prognostic significance for age, dyspnea, initial tracheostomy, and
      pathologic lymph node status. No difference was found when comparing survival and
      relapse rates between transglottic and glottic tumors. CONCLUSION: Surgery
      provides acceptable rates of cancer control and survival for patients with T3
      glottic carcinoma. Older patients, patients with positive neck nodes, and those
      presenting with dyspnea have worse prognosis. The term transglottic is merely
      descriptive and has little impact on prognosis.

PMID- 11337663
TI  - Surgical treatment for hypopharynx carcinoma: feasibility, mortality, and
      results.
AB  - This study seeks to evaluate treatment modalities, mortality after surgery,
      survival, and local control rates for a consecutive cohort of patients with
      cancer of the hypopharynx treated according to a prospective protocol that favors
      surgery as an initial approach to the disease. The charts of 228 consecutive
      patients with previously untreated hypopharyngeal squamous cell carcinoma were
      reviewed. Outcome measures (overall survival, disease specific survival, and
      local control) were calculated using the Kaplan-Meier estimator. Of 228
      consecutive patients, 136 (59.6%) were found suitable for initial surgical
      treatment. Of the remaining 92 patients, 18 (7.9%) had nonresectable lymph node
      metastases, 16 (7.0%) had unresectable primary tumors, 13 (5.7%) refused surgery,
      and 13 (5.7%) presented distant metastases during initial diagnostic evaluation.
      Of those who had surgery, 46 had larynx-sparing procedures, 54 had total
      laryngectomy, and 36 had total laryngo-pharyngectomy. None of the patients who
      had surgery died postoperatively. Actuarial 5-year overall survival was 27.2% for
      all 228 patients, 39.5% for the 136 patients with surgical treatment, and 61.1%
      for the 46 patients who were treated with larynx-sparing procedures.

PMID- 11337664
TI  - Free radical damage in nasal polyp tissue.
AB  - OBJECTIVE: To investigate whether the free radical injury in nasal polyp tissue
      exists or not. STUDY DESIGN: A prospective study in patients with nasal polyps.
      METHODS: Polyp specimens were obtained from 19 patients. Control specimens were
      acquired from 16 patients who underwent partial turbinectomy with concha bullosa
      free of rhinitis, sinusitis, and allergy, confirmed by endoscopic nasal
      examination, coronal paranasal sinus CT scan, and prick test. MDA levels of nasal
      polyps and control specimens were measured by using the method of Knudsen et al.
      RESULTS: The mean MDA levels of nasal polyps and control specimens were 38.2 +/-
      5.1 (33.3-52.2) and 33.9 +/- 1.6 (32.6-37.4), respectively. MDA levels in NP were
      significantly higher compared with control specimens (P < 0.01). CONCLUSION: High
      level of MDA in nasal polyp tissue that represents FR increase supports the
      existence of cell injury in nasal polyp tissue. FRs should be considered in the
      development and life cycles of NP which is thought to have multifactorial
      pathogenesis.

PMID- 11337665
TI  - Toxic shock syndrome associated with frontal sinus stents.

PMID- 11337666
TI  - Laryngeal paresis as a presenting feature of idiopathic brachial plexopathy.

PMID- 11337667
TI  - Unusual presentation of a saccular cyst in a teenager.

PMID- 11337668
TI  - Lymphatic malformation with internal jugular phlebectasia.

PMID- 11337669
TI  - Neurofibromatosis type 2 associated with cranial nerve schwannomas.

PMID- 11337670
TI  - Huge nasopharyngeal true teratoma with cleft palate and lip and unilateral
      choanal atresia.

PMID- 11337671
TI  - Respiratory implantation cyst of the mandible after chin augmentation: report of
      case.

PMID- 11337672
TI  - Nontraumatic arteriovenous fistula of the superficial temporal artery.

PMID- 11337673
TI  - How did it get there? A coiled metal foreign body in an unusual cervical
      position.

PMID- 11337674
TI  - Acute bilateral sensorineural hearing loss as the presenting symptom of
      metastatic lung cancer.

PMID- 11337675
TI  - Munchausen's syndrome: a case report with multiple symptoms.

PMID- 11337676
TI  - Kimura's disease of the auricle.

PMID- 11337677
TI  - Transtympanic stimulation of the facial nerve to assess nerve integrity in
      iatrogenic facial nerve paralysis.

PMID- 11337678
TI  - Color-coded tissue Doppler assessment of the effects of acute ischemia on
      regional left ventricular function: comparison with sonomicrometry.
AB  - Echocardiographic assessment of regional left ventricular (LV) function usually
      consists of subjective visual inspection of endocardial movement and wall
      thickening. Color-coded tissue Doppler (TD) is a potential means to quantify
      regional LV function more objectively. Accordingly, in this study, color-coded TD
      was used to assess the regional effects of acute ischemia in an open-chest canine
      model of coronary occlusion, with implanted sonomicrometry length crystals as a
      standard of reference. Eight dogs were studied during baseline conditions and
      during left anterior descending coronary artery occlusion. Midventricular short
      axis images were used to guide the color TD M-mode cursor through circumflex
      (septal) and left anterior descending (anterolateral) perfusion zones. Off-line
      conversion of endocardial time-velocity maps was performed. Peak systolic
      endocardial velocity by TD decreased from 4.4 +/- 1.4 cm/s to 1.8 +/- 1.5 cm/s
      with coronary occlusion (P < .05 versus baseline). Similar significant decreases
      in calculated systolic velocity by sonomicrometry occurred with ischemia from
      11.1 +/- 3.8 mm/s to 8.2 +/- 1.2 mm/s (P < .05 versus baseline). Peak systolic
      velocity by TD was inversely correlated with end-systolic length by
      sonomicrometry as a measure of regional function (r = -0.77, P < .001). Time to
      peak systolic velocity increased with ischemia from 154 +/- 60 ms to 286 +/- 67
      ms by TD and 200 +/- 60 ms to 320 +/- 30 ms by sonomicrometry (P < .05 versus
      baseline). The delay in time to peak systolic velocity by TD and sonomicrometry
      were correlated (r = 0.75, P < .001). In conclusion, color-coded TD
      echocardiography has the potential to quantify regional LV function during
      coronary ischemia.

PMID- 11337679
TI  - Assessment of ventricular filling volumes with an automated color Doppler method:
      validation in a pulsatile flow model.
AB  - OBJECTIVE: Determination of ventricular filling volumes with the use of Doppler
      echocardiographic measurements critically depends on the presence of a circular
      shaped flow area and a flat velocity profile across it because evaluation of flow
      volume is usually based on echocardiographic measurements of its diameter and
      pulsed Doppler recordings within the center of this area. The approach may be
      limited at the mitral and tricuspid ring levels as a result of their noncircular
      shape and because nonflat velocity profiles are present. The purpose of this
      study was to examine in a pulsatile flow model simulating ventricular inflow
      conditions the accuracy of an automated method based on the analysis of color
      Doppler flow velocities for evaluation of flow volumes. MATERIALS AND METHODS: A
      recently-developed automated Doppler method that takes into account the velocity
      distribution across a region of interest was examined in a pulsatile flow model
      by using flows with waveforms characteristic for ventricular inflow through tubes
      with elliptically-shaped cross-sectional areas. Color Doppler imaging was
      performed against flow direction along the major and minor axes of the tubes with
      major diameters ranging between 3 and 5 cm and major-to-minor diameter ratios of
      1.5 and 2.0. RESULTS: A close correlation was found between flow volumes measured
      by the Doppler technique for registrations along the minor or major axis of the
      ellipses and actual values (r = 0.99, standard error of the estimate = 0.44 to
      1.98 mL), with a systematic underestimation or overestimation, respectively,
      depending on the diameter ratio. Averaging of the data derived from 2 orthogonal
      measurements by using the geometric mean value yielded an excellent agreement
      between Doppler data and actual flow volumes. CONCLUSION: This automated color
      Doppler method enables reliable determination of flow volumes in a pulsatile flow
      model simulating ventricular inflow conditions with the use of 2 orthogonal
      imaging views. The data indicate that the method may improve the noninvasive
      evaluation of ventricular filling volumes.

PMID- 11337680
TI  - Tissue Doppler imaging enables the identification of diastolic dysfunction of
      pseudonormal pattern in Chagas' disease.
AB  - The Doppler pseudonormal pattern of left ventricular (LV) diastolic function
      filling, characterized by apparent normal transmitral flow velocities, indicates
      advanced diastolic dysfunction with abnormal relaxation and compliance. Left
      ventricular diastolic dysfunction has been shown to occur in the early stages of
      the outcome of Chagas cardiopathy, and its identification may potentially
      contribute to the management of those patients. The aim of this study was to
      evaluate the usefulness of tissue Doppler imaging (TDI) in identifying LV
      diastolic dysfunction in patients with Chagas' disease with pseudonormal
      transmitral flow. For this purpose, 89 patients with Chagas' disease (48 men) who
      had no other pathology and showed normal (n = 79) or pseudonormal (n = 10)
      patterns of diastolic function by pulsed wave Doppler were submitted to TDI. A
      significant LV systolic impairment in terms of the dimensions (P = .00001),
      ejection fraction (P = .000001), and wall motion score (P = .000002) was observed
      in patients with diastolic dysfunction when compared with the group with normal
      LV diastolic function. Tissue Doppler imaging enabled the recognition of a
      pseudonormal type of transmitral flow velocity with high statistical significance
      through early (P = .000008) and late (P = .0003) expansion waves. The sensitivity
      and specificity in detecting LV diastolic dysfunction with TDI in the septal,
      anterior, inferior, posterior, and lateral walls were 90% and 87.3%, 87.3% and
      90%, 87.3% and 90%, 84.8% and 90%, and 84.8 and 90%, respectively. In conclusion,
      TDI enabled the differentiation of patients with Chagas' disease with normal LV
      diastolic function and those with the pathologic LV pseudonormal pattern with
      high statistical significance. Moreover, this article shows the potential in
      demonstrating the occurrence of major alterations in the LV performance of
      patients with Chagas' disease with LV diastolic dysfunction, as well as the
      occurrence of signs of an increased LV filling pressure in those patients.

PMID- 11337681
TI  - Real-time strain rate echocardiographic imaging: temporal and spatial analysis of
      postsystolic compression in acutely ischemic myocardium.
AB  - Postsystolic compression (PSC) is a sensitive indicator of regional left
      ventricular ischemic diastolic dysfunction. Quantitative assessment of
      compression patterns by strain rate imaging could determine the presence and
      spatial extent of PSC for the detection and analysis of acute ischemic diastolic
      dysfunction. With the use of a segmental left ventricular model, we evaluated
      time to compression/expansion crossover (T-CEC) in standard apical views. Data at
      baseline and after acute left anterior descending coronary artery occlusion were
      collected from 18 open-chest pigs. We found significant mean prolongation of T
      CEC, ranging from 43.9 +/- 48.6 ms to 110.8 +/- 73.8 ms, in all apical segments
      and in 2 midventricular (anterior and anteroseptal) segments. Analysis of
      variance demonstrated that the prolonged T-CEC is spatially consistent with
      perfusion defect. The temporal and spatial analysis of T-CEC with the use of
      strain rate imaging is a new noninvasive technique for identification and
      topographic quantitation of ischemic diastolic dysfunction expressed by PSC.

PMID- 11337682
TI  - Evaluation of septal hypertrophy and systolic function in diseases that cause
      left ventricular hypertrophy: a 3-dimensional echocardiography study.
AB  - OBJECTIVES: The goals of this study were to determine regional systolic function
      of the septum and to relate it to regional wall thickness and wall stress.
      BACKGROUND: Wall thickening, a parameter of systolic function, is determined by
      wall thickness and wall stress. In patients with hypertrophic obstructive
      cardiomyopathy (HOCM), hypertrophic nonobstructive cardiomyopathy (HNCM), and
      hypertensive heart disease (HHD), regional systolic function of normal and
      hypertrophic septal regions has been incompletely characterized by 2-dimensional
      echocardiography. Thus, multiplane transesophageal echocardiography with 3
      dimensional reconstruction of the septum was used. METHODS AND RESULTS: In 49
      patients (15 controls, 11 with HOCM, 8 with HNCM, and 15 with HHD) 4 parallel (2
      basal and 2 apical) equidistant short-axis cross sections from base to apex were
      obtained from the reconstructed septum. In each short-axis cross section, 6 wall
      thickness measurements were made in 15 degrees intervals at end diastole and end
      systole, for a total of 48 measurements in each patient. Fractional thickening
      was calculated as wall thickening divided by end-diastolic wall thickness. Wall
      thickness of the basal cross sections was significantly thicker (P < .001) in
      HOCM and HNCM than in HHD. However, circumferential wall thickness was more
      evenly distributed in HNCM and HHD when compared with HOCM. In the basal cross
      sections, fractional thickening was similarly reduced in all hearts, though basal
      wall stress was significantly different in all groups (P < .001). In the apical
      cross sections, wall thickness was similar in all diseased hearts, but fractional
      thickening was better (P < .001) and wall stress lower (P < .001) in HNCM than in
      HOCM and HHD. CONCLUSIONS: In septal regions without or with only mild
      hypertrophy, regional systolic function is preserved and appears to be determined
      by hemodynamic factors such as wall stress. However, in regions with moderate to
      severe hypertrophy, systolic function is markedly and uniformly impaired in all
      groups, which seems not to be caused by differences in wall thickness and wall
      stress but by the degree of the myocardial disease process.

PMID- 11337683
TI  - Contrast dobutamine stress echocardiography: clinical practice assessment in 300
      consecutive patients.
AB  - In this study we compared non-contrast imaging with contrast imaging of the left
      ventricle during dobutamine stress echocardiography (DSE). Wall segment
      visualization, image quality, and confidence of interpretation were determined
      with and without the use of intravenous Optison, a second-generation
      echocardiographic contrast agent, in 300 consecutive patients undergoing rest and
      peak DSE. At rest and at peak stress, the percentage of wall segments visualized,
      image quality, and confidence of interpretation were better with contrast
      compared with non-contrast imaging. No significant decrease was seen in wall
      segment visualization, image quality, or confidence of interpretation from rest
      to peak stress in images obtained with contrast, unlike the images obtained
      without contrast from rest to peak stress. The use of the intravenous
      echocardiographic contrast agent Optison during DSE significantly improved wall
      segment visualization and image quality at rest and at peak stress, resulting in
      improved confidence of interpretation.

PMID- 11337684
TI  - Pulmonary venous flow in large, uncomplicated atrial septal defect.
AB  - BACKGROUND: The pulmonary venous flow velocity pattern (PVFVP) in atrial septal
      defect (ASD) has not been previously studied in detail. Normally, PVFVP is
      primarily determined by the left heart performance. We hypothesized that the
      impact of left-sided heart dynamics on PVFVP is diminished in patients with ASD
      because of the presence of a left-to-right shunt into the low-resistance right
      side of the heart. METHODS AND RESULTS: Transesophageal echocardiography was
      performed in 19 adults and 3 children with a large, uncomplicated secundum ASD
      (maximum diameter 0.6 to 3.0 cm). All patients were in normal sinus rhythm with
      an average heart rate of 78 bpm in adults and 116 bpm in children. In 21 subjects
      the antegrade PVFVP lacked distinct systolic (S) and diastolic (D) waves.
      Instead, we observed a single continuous antegrade wave extending from the
      beginning of systole to the onset of atrial contraction. Furthermore, the
      amplitude of the atrial reversal (AR) wave was smaller than in historical
      controls. In 3 patients in whom ASD was surgically repaired, we observed an
      immediate return of distinct S and D waves postoperatively. This confirmed that
      PVFVP abnormality was indeed the result of the ASD. Also a large increase in the
      AR wave amplitude (46 + 15 cm/s) was noted postoperatively. CONCLUSIONS: This
      previously unrecognized PVFVP comprising a single continuous antegrade wave and a
      diminished AR wave sheds new light on the hemodynamics of ASDs. Its presence may
      also alert the echocardiographer to the possibility of an ASD when the septal
      defect cannot be visualized directly.

PMID- 11337685
TI  - Does atrioventricular ring motion always distinguish constriction from
      restriction? A Doppler myocardial imaging study.
AB  - Constrictive pericarditis and restrictive cardiomyopathy can be difficult to
      differentiate on clinical examination. Cardiac ultrasonography is increasingly
      being used as the noninvasive method of choice for confirming the specific
      morphologic and hemodynamic abnormalities associated with either condition.
      Interrogation of atrioventricular valve plane motion by Doppler myocardial
      imaging (DMI) has been suggested as a valuable new approach that can help
      differentiate one from the other. We report the color DMI, pulsed DMI, and strain
      rate findings in 2 cases of constrictive pericarditis in which consideration of
      the annular motion pattern alone would not have allowed such differentiation.

PMID- 11337686
TI  - Thromboembolus from a ligated left atrial appendage.
AB  - The left atrial appendage of patients with mitral valve disease is commonly a
      source of thromboembolus and is often ligated during mitral valve surgery to
      diminish this risk. However, ligation is often incomplete. We describe a patient
      with a stroke whose only source of embolus was an incompletely ligated left
      atrial appendage. Attempts to exclude the left atrial appendage from the arterial
      circulation by suture ligation may not decrease the risk of thromboemboli and
      instead may increase such risk.

PMID- 11337687
TI  - Transesophageal echocardiographic abnormalities in a case of cardiac sarcoidosis.
AB  - Sarcoidosis is a granulomatous disease that may involve multiple organ systems,
      including the heart. Manifestations include atrial and ventricular arrhythmias,
      conduction abnormalities, congestive cardiac failure, pericarditis, and sudden
      death. Whereas cardiac involvement is a relatively common finding at autopsy,
      antemortem diagnosis is often missed because the clinical manifestations are
      nonspecific, and the sensitivity and specificity of investigations are low. We
      report a case of a 62-year-old woman who had clinically significant cardiac
      sarcoidosis associated with echocardiographic abnormalities that had not been
      reported previously in association with this condition.

PMID- 11337688
TI  - Three-dimensional echocardiography: historical development and current
      applications.
AB  - Three-dimensional (3D) echocardiography facilitates spatial recognition of
      intracardiac structures, potentially enhancing diagnostic confidence of
      conventional echocardiography. The accuracy of 3D images has been validated in
      vitro and in vivo. In vitro, a detail 1.0 mm in dimension and 2 details separated
      by 1.0 mm can be identified from a volume-rendered 3D image. In vitro 3D volume
      measurements are underestimated by approximately 4.0 mL. In vivo, left
      ventricular volume measurements correlate highly with both cineventriculography
      (limits of agreement +/-18 mL for end diastole and +/-10 mL for end systole) and
      magnetic resonance imaging, including measurements for patients with functionally
      single ventricles. Studies on congenital heart lesions have shown good accuracy
      and good reproducibility of dynamic "surgical" reconstructions of septal defects,
      aortoseptal continuity, atrioventricular junction, and both left and right
      ventricular outflow tract morphology. Transthoracic 3D echocardiography was shown
      feasible in 81% to 96% of patients with congenital heart defects and provided
      additional information to that available from conventional echocardiography in
      36% of patients, mainly in more detailed description of mitral valve morphology,
      aortoseptal continuity, and atrial septum. In patients with mitral valve
      insufficiency, 3D echocardiography was shown to be accurate in the quantification
      of the dynamic mechanism of mitral regurgitation and in the assessment of mitral
      commissures in patients with mitral stenosis. This includes not only valve tissue
      reconstruction but also color flow intracardiac jets. Three-dimensional
      reconstructions of the aortic valve were achieved in 77% of patients, with an
      accuracy of 90%. In conclusion, the role of 3D echocardiography, which continues
      to evolve, shows promise in the assessment of congenital and acquired heart
      disease.

PMID- 11337689
TI  - Myocardial function in ischemic heart disease.

PMID- 11337691
TI  - Positive pressure ventilation reverses the pattern of respiratory variation of
      Doppler inflow velocities in constrictive pericarditis.

PMID- 11337693
TI  - Guidelines for the cardiac sonographer in the performance of contrast
      echocardiography: recommendations of the American Society of Echocardiography
      Council on Cardiac Sonography.

PMID- 11337695
TI  - Collective strength.

PMID- 11337696
TI  - Measurement challenges in fecal incontinence.

PMID- 11337697
TI  - Qualitative research: a different paradigm--part 2.

PMID- 11337698
TI  - Clean versus sterile technique when changing wound dressings.

PMID- 11337699
TI  - Health maintenance in a primary care clinic for urban, indigent adults.
AB  - OBJECTIVE: The objective was to examine the delivery of preventive health care
      services in an urban clinic for indigent adults and the impact of advanced
      practice nursing on these practices. DESIGN: The study design was a descriptive
      chart review. SETTING AND SUBJECTS: Data were collected in an urban outpatient
      clinic. Seven hundred sixty-five records were examined prospectively for health
      maintenance. Of these records, 523 were randomly selected and reviewed
      retrospectively for completion of health maintenance. The mean age of
      participants was 45.15 years (SD = 9.87); 92% were African American, and 48.9%
      were male. INSTRUMENTS: The Health Maintenance Form was used to record data about
      demographics, health history, care provider, and completion of 10 health
      maintenance items. METHODS: Records were reviewed prospectively prior to the
      patient's clinic visit. A form summarizing the patient's health maintenance
      status was placed at the front of the record. At least 4 weeks later, the record
      was reviewed a second time for completion of health maintenance items. This
      second review was the data collection phase. RESULTS: Completion of health
      maintenance items was found to be low. The most up-to-date areas were serum
      cholesterol (83.9%) and mammography (70.1%). The lowest levels were rectal
      examination (34.5%), pneumococcal vaccination (35%), and fecal occult blood test
      (37.1%). Patients followed up by a nurse practitioner had significantly more
      health maintenance areas up-to-date than did patients followed-up by the nurse
      practitioner-physician team, which in turn had significantly more areas up-to
      date than did patients followed up by a physician alone. CONCLUSIONS: Health
      maintenance was accomplished at a low level, indicating that preventive health
      practices need to be re-evaluated. The nurse practitioner had the greatest impact
      on a patient's health maintenance being up-to-date.

PMID- 11337700
TI  - A critical review of the literature: part II: antibiotic treatment of
      osteomyelitis in patients with diabetes and foot ulcers.
AB  - The diagnosis and treatment of osteomyelitis in the diabetic patient with a foot
      ulcer presents a difficult challenge for WOC nurses. Treatments vary greatly in
      terms of time, cost, and invasiveness, as does the accuracy of the underlying
      diagnosis. For example, the choice of oral versus parenteral antibiotics, the
      length of therapy, and decisions about surgical intervention or aggressive
      debridement are based on accurate differentiation of osteomyelitis from soft
      tissue infection, osteoarthropathy, or other related conditions. This article is
      the second of a critical literature review designed to identify the best evidence
      for diagnosing and treating osteomyelitis in patients with diabetes. It focuses
      on the existing evidence base for antibiotic therapy.

PMID- 11337701
TI  - How the principles of exercise physiology influence pelvic floor muscle training.
AB  - Clinicians have used pelvic floor muscle training as a behavioral treatment for
      urinary incontinence for the past 50 years. Various protocols for training these
      muscles have been tested. Evidence has shown that strengthening the pelvic floor
      muscle can diminish, and sometimes eliminate, involuntary urine loss. The purpose
      of this article is to describe the principles of exercise physiology and the role
      these principles play in shaping pelvic floor muscle training regimens.
      Fundamental content regarding lower urinary tract physiology, specific to the
      pelvic floor muscles, and muscle fiber differentiation is presented to provide
      the foundation for a case study description of pelvic floor muscle training
      within the framework of these principles.

PMID- 11337702
TI  - Methodology of biofeedback for adults with fecal incontinence: a program of care.
AB  - In a previous article we described a nursing assessment for adults with fecal
      incontinence. This article outlines in detail the program of care, tailored to an
      individual's assessed needs, that is available in the nurse-led biofeedback
      service for fecal incontinence at St Mark's Hospital in England. A recent
      evaluation of this program found that two thirds of patients reported improved
      fecal continence after receiving care from this service.

PMID- 11337703
TI  - Special delivery: a biofeedback program for fecal incontinence.

PMID- 11337704
TI  - Care of an obese patient with a pressure ulcer.

PMID- 11337705
TI  - Acromion reconstruction after total arthroscopic acromionectomy: Salvage
      procedure using a bone graft.
AB  - We report 2 cases of acromion reconstruction with a bone graft as a salvage
      procedure after total arthroscopic acromionectomy. Complete removal of the
      acromion had produced severe shoulder abnormality with pain and joint stiffness.
      We present the operative technique of acromion reconstruction using a
      corticocancellous bone graft from the iliac crest. Recreation of the acromion as
      a fulcrum of the shoulder joint as well as an important physiological insertion
      area for the deltoid muscle markedly improved pain and range of motion in these
      patients. In conclusion, based on these cases, we believe that total
      acromionectomy is an inadequate procedure for treatment of shoulder impingement
      syndrome. Acromion reconstruction with a bone graft is an alternative that may
      lead to improvement of clinical symptoms.

PMID- 11337706
TI  - Rice bodies of synovial origin in the knee joint.
AB  - Rice bodies are free corpuscles of synovial origin with a cartilage-like
      appearance that may reach hundreds in number in the intra-articular space.
      Rheumatologic or infectious pathologies that may produce synovial hypertrophy
      play a major role in the etiology. Already recognized by rheumatologists, this
      entity is rarely reported in orthopaedic literature. Numerous particles in the
      size and form of rice bodies were noted in the knee joint of an 11-year-old
      patient who underwent arthroscopic drainage and partial synovectomy.
      Histopathologic examination showed that some of the rice bodies consisted only of
      fibrin and some of them included a collagenous nucleus surrounded by a fibrin
      layer. No evidence of recurrence was observed by orthopaedic and rheumatologic
      evaluations within 2.5 years after the arthroscopic procedure.

PMID- 11337707
TI  - Type III tibial avulsion fracture with associated anterior cruciate ligament
      injury: Report of two cases in adults.
AB  - Tibial spine avulsion fractures are more common in children than adults. Many
      reports have provided classification and treatment options, including fixation
      for displaced type III fractures. However, long-term follow-up on injury to the
      anterior cruciate ligament and knee joint stability in adults is not well
      documented. We present 2 cases of type III tibial avulsion fractures in adults
      with associated interstitial injury to the anterior cruciate ligament. Primary
      anterior cruciate ligament reconstruction was performed in both patients.

PMID- 11337708
TI  - Arthroscopic localization of medial collateral ligament injury: Report of 2 cases
      in adults.
AB  - Injury to the medial collateral ligament has previously been assessed primarily
      using the clinical examination and magnetic resonance imaging. In this article,
      we describe an adjunct to these diagnostic tools: an arthroscopic observation to
      assess the specific location of the medial collateral ligament injury.

PMID- 11337709
TI  - Biomechanical investigations of different meniscal repair implants in comparison
      with horizontal sutures on human meniscus.
AB  - PURPOSE: The use of biodegradable implants for arthroscopic repair of meniscal
      lesions is becoming increasingly popular. The aim of this study was to test the
      biomechanical stability and the mode of failure of these implants. TYPE OF STUDY:
      Biomechanical testing study. METHODS: Biomechanical investigations were performed
      on human menisci using 6 commonly used biodegradable implants for meniscal repair
      to compare them with horizontal mattress suture using 2/0 Ethibond (Ethicon,
      Norderstedt, Germany). Included in this study were the Meniscus Arrow (Bionx,
      Tampere, Finland), Dart (Arthrex, Naples, FL), Stinger (Linvatec, Largo, FL),
      Meniscal Screw (Innovasive, Marlborough, MA), T-Fix (Acufex, Mansfield, MA), and
      the Fastener (Mitek, Westwood, MA). The tests were carried out using a material
      testing machine at a loading rate of 10 N/second. The ultimate tension load
      (UTL), elongation, and stiffness were evaluated for each implant technique.
      RESULTS: The highest UTL was shown by Ethibond (62 +/- 7.91 N) and the T-Fix
      (51.35 +/- 16.31 N), followed by the Fastener (32.67 +/- 2.97 N). All other
      implants had a significantly lower UTL (P =.001). Less elongation under a load of
      5 N was noted for Ethibond (0.64 +/- 0.25 mm) and for T-Fix (0.43 +/- 0.32 mm)
      compared with the other implants. The greatest elongation was found for the
      Fastener (2.239 +/- 0.581 mm). The stiffness of the fixation was similar in all
      implants, except for the Dart and Fastener, which were significantly inferior (P
      <.05). CONCLUSIONS: All of the biodegradable implants had lower UTL than the
      suture techniques. Therefore, when using the implants, they should be inserted
      close together to provide sufficient stability. In cases of an extended lesion,
      there might even be an option to combine the implant and suturing techniques.

PMID- 11337710
TI  - Magnetic resonance imaging follow-up study of bone bruises associated with
      anterior cruciate ligament ruptures.
AB  - PURPOSE: The purpose of this study was to perform a magnetic resonance imaging
      (MRI) follow-up study of bone bruises in a group of patients with acute anterior
      cruciate ligament (ACL) ruptures that were reconstructed and followed-up for a
      minimum of 2 years. TYPE OF STUDY: Cohort study. METHODS: The study group
      included 21 patients with a mean age of 31 years whose initial MRI scans showed
      associated bone bruises. Patients were included if they had an acute isolated ACL
      tear, no documentation of an episode of repeated injury to the affected knee
      during the follow-up period, and no evidence of cartilaginous injury at the time
      of arthroscopy. All patients had preoperative MRI scans and underwent
      arthroscopic ACL reconstruction using a bone-patellar tendon autograft an average
      of 2 months after injury. The preoperative MRI scans were analyzed using a 3
      level grading system based on the appearance and location of bone bruises. A
      second MRI of the knee was obtained from 24 to 64 months postoperatively (average
      34 months). The presence of resolution of bone bruises was determined and
      correlation with clinical scoring established. RESULTS: This study showed
      resolution of all type I lesions and 91% of type II lesions (10 of 11). In all
      type III lesions, an articular cartilage thinning and depression was observed
      after 2 years of follow-up. In 15 patients (71%), MRI showed that the bone
      bruises had resolved without apparent sequelae. In the remaining 6 patients
      (29%), sequelae of the osteochondral lesion were evident on MRI. CONCLUSIONS:
      According to our clinical data, there was no correlation between scores obtained
      from patients with resolved lesions against those with osteochondral sequelae.
      Although long-term clinical implications of these findings are uncertain, a
      severe occult osteochondral lesion sustained at the time of ACL rupture seems to
      be persistent on MRI even after a successful reconstruction.

PMID- 11337711
TI  - Arthroscopic fixation of intercondylar eminence fractures using a 4-portal
      technique.
AB  - PURPOSE: We report an easy-to-use 4-portal technique for arthroscopic treatment
      of intercondylar eminence fractures and compare results of 2 groups of cases,
      adolescents and adults, and 2 types of internal fixation, sutures and screws.
      TYPE OF STUDY: Surgical technique and retrospective study. METHODS: The study was
      carried on 2 groups of patients, adolescents and adults, with intercondylar
      eminence fractures who were treated arthroscopically. For internal fixation,
      sutures were used in 8 adolescents and screws were used in 13 adults. In the
      technique we describe, anteromedial superior and inferior, and anterolateral
      superior and inferior portals were used. RESULTS: The average follow-up period
      for the adolescents was 27.3 months (range, 11 to 57 months), and for the adults
      was 19.6 months (range, 7 to 71 months). We did not encounter any cases of
      nonunion. There were only 3 complications, 1 of arthrofibrosis resulting from a
      delay of rehabilitation due to a vascular compromise and 2 cases of tenderness
      over the screw that responded well to its removal. Union occurred earlier in
      adolescents, but rehabilitation was easier in adults. CONCLUSIONS: Beside
      satisfactory results obtained by arthroscopic treatment of intercondylar eminence
      fractures, arthroscopy also provides the possibility to determine and treat
      associated pathologies. With the experience we gained, the procedure with the 4
      portal technique in treating these fractures became much easier as a routine
      approach.

PMID- 11337712
TI  - Comparisons of intraosseous graft healing between the doubled flexor tendon graft
      and the bone-patellar tendon-bone graft in anterior cruciate ligament
      reconstruction.
AB  - PURPOSE: The purpose of this study was to compare intraosseous graft healing
      between the doubled flexor tendon (FT) graft and the bone-patellar tendon-bone
      (BPTB) graft in anterior cruciate ligament (ACL) reconstruction. TYPE OF STUDY:
      Randomized trial. METHODS: A biomechanical and histologic study was conducted
      with 24 adult beagle dogs. Bilateral ACL reconstructions were performed in each
      animal. Autogenous doubled FT and BPTB grafts were used for the left and right
      knees, respectively. Each end of the 2 grafts was tethered with a polyester
      suture to a screw post with a washer. The animals were then allowed unrestricted
      activities in their cages. Eight animals were killed at 3, 6, and 12 weeks,
      respectively. RESULTS: Histologically, the FT graft was anchored to the tunnel
      wall with newly formed collagen fibers resembling Sharpey's fibers by 12 weeks.
      These fibers were more abundant in the anterior (ventral) gap than in the
      posterior (dorsal) gap. In the BPTB graft, the bone plug was anchored with newly
      formed bone at 3 weeks, although osteocytes in the plug trabeculae were necrotic
      for 12 weeks. Degeneration of the tendon-bone junction in the plug progressed at
      6 weeks. Tensile testing showed that the weakest site was different not only
      between the 2 grafts but also between the observation periods. In the FT graft,
      the weakest site was the graft-wall interface at 3 weeks and the intraosseously
      grafted tendon at 6 weeks. In the BPTB graft, the weakest site was the graft-wall
      interface at 3 weeks and the proximal site in the bone plug at 6 weeks. The
      ultimate failure load of the FT graft was significantly inferior (45.8%) to that
      of the BPTB graft at 3 weeks (P =.021). At 6 weeks, the load of the FT graft was
      85% that of the BPTB graft without a significant difference (P =.395).
      CONCLUSIONS: As to the clinical relevance, the fixation device chosen for soft
      tissue fixation appears to be more important than comparing it to the BPTB graft,
      although this has yet to be conclusively proven.

PMID- 11337714
TI  - Chondral lesions of the knee: A new localization method and correlation with
      associated pathology.
AB  - PURPOSE: We report a new method of describing and recording chondral lesions of
      the knee at arthroscopy in order to permit a more accurate and meaningful
      analysis of patterns of articular cartilage damage. TYPE OF STUDY: Case series
      study. METHODS: Data were collected prospectively at 1,000 consecutive
      arthroscopies by the senior author and chondral lesions were recorded on anatomic
      articular maps divided into different functional zones. Ten zones on the femur
      were determined by tibiofemoral weight-bearing and flexion horizons (namely the 0
      degrees, 45 degrees, 90 degrees, and 120 degrees horizons as they pass the
      anterior meniscosynovial junction). Ten zones were determined on the tibia,
      principally by meniscal relations, and 6 zones on the patella. This allowed the
      size, Outerbridge grade, and location to be analyzed in relation to mechanism,
      chronicity, and associated intra-articular pathologies. The recording methods
      were tested for interobserver reproducibility in 50 subsequent cases at the same
      arthroscopy by 2 independent observers. The results were analyzed by a third
      person, and showed a relatively small interobserver error of 7.2% for size for a
      set of grade 3 and 4 lesions and only a 3% error for site. The Fisher exact test
      was used. The data sheets were entered onto a computer spreadsheet database using
      standard software (Excel; Microsoft, Redmond, WA) to permit analysis of the data.
      RESULTS: There were 1,553 chondral lesions in 853 patients correlated with
      associated lesions, including 356 meniscal lesions, 230 ligamentous injuries, 440
      synovial lesions, and other pathologies. High degrees of correlation have been
      found between specific lesions and their opposing surfaces and the progression of
      these with time. CONCLUSIONS: The problem of precision of localization of
      articular lesions in the knee has been recently acknowledged by the International
      Cartilage Research Society (ICRS). However, such recording ought to take into
      account both function and contact with other structures. This would appear
      essential in the assessment of prognosis and comparisons between different
      treatment regimes.

PMID- 11337713
TI  - Comparison of morphine and ropivacaine following knee arthroscopy.
AB  - PURPOSE: The purpose of this study was to compare the effectiveness of
      ropivacaine, a new local amidic anesthetic, compared with morphine as an intra
      articular drug in controlling pain in patients after arthroscopic knee surgery.
      TYPE OF STUDY: Randomized trial. METHODS: We enrolled 90 patients scheduled to
      undergo elective knee arthroscopy. Patients were homogenous regarding demographic
      data and ASA physical status. Procedures included were diagnostic arthroscopies,
      lateral and medial meniscectomies, meniscal repair, and removal of loose bodies.
      All cases were treated by the same surgeon, under general anesthesia, using the
      same procedure. Patients were randomly divided into 3 groups. The first group
      received ropivacaine 75 mg in 20 mL of saline solution, the second group received
      2 mg morphine in 20 mL of saline solution, and the third group received 20 mL of
      saline solution. No other oral or injectable analgesic administration was
      allowed. A blind observer assessed the patients' postoperative pain using a 10-cm
      visual analogue scale (VAS), ranging from no pain (0) to unbearable pain (10).
      Scores were taken at 0, 1, 4, 6, 12, and 24 hours after drug injection. VAS
      scores were analyzed using analysis of variance; significance was set at P <.005.
      RESULTS: None of the patients treated with ropivacaine or morphine needed
      administration of any other oral or injectable analgesic. No adverse reaction was
      noted in ropivacaine group. VAS score analysis in the first 4 postoperative hours
      showed greater effectiveness for ropivacaine versus morphine or placebo with
      highly significant results (P <.001). In the first 24 postoperative hours, the
      ropivacaine group versus the morphine group showed no significant differences (P
      =.207). CONCLUSIONS: Although its cost is very high compared with morphine,
      ropivacaine is a safe, site-specific, and long lasting anesthetic drug with an
      earlier onset than morphine and almost the same duration, covering the whole
      postoperative period (24 hours).

PMID- 11337715
TI  - Snapping plicae associated with radiocapitellar chondromalacia.
AB  - PURPOSE: Painful snapping of the elbow joint is usually attributed to intra
      articular loose bodies, instability, or medial dislocation of the triceps muscle
      over the medial epicondyle. We report our experience with 14 patients who were
      treated arthroscopically for snapping elbow that was found to be caused by
      hypertrophic synovial folds associated with radiocapitellar chondromalacia. TYPE
      OF STUDY: Case series. METHODS: The records of 14 patients who were treated
      arthroscopically for painful snapping elbows caused by intra-articular plicae
      were reviewed. There were 6 women and 8 men with an average age of 36 years
      (range, 27 to 48 years). Nine patients had had some type of trauma to the joint.
      Four patients had been previously diagnosed with lateral epicondylitis and 5 with
      intra-articular loose bodies. The average time from initial onset of symptoms to
      treatment was 13 months (range, 8 to 36 months). Average follow-up was 24 months
      (range, 6 to 66 months). RESULTS: All patients complained of painful snapping in
      the posterolateral or anterolateral aspect of the elbow. The snapping occurred
      between 90 degrees and 110 degrees of flexion with the forearm in pronation. In 7
      patients, the snapping was reproducible by passively flexing the pronated elbow,
      which we refer to as the flexion-pronation test. At the time of arthroscopic
      surgery, all patients had a thickened synovial plica that would snap back and
      forward over the radial head, usually associated with a chondromalacic area on
      the radial head. Twelve patients had complete relief of their snapping after
      surgery. One patient in whom there was associated posterolateral rotatory elbow
      instability did not improve. One patient became asymptomatic for 4 years but then
      had recurrence of her symptoms, which persisted despite 2 subsequent
      arthroscopies. CONCLUSIONS: The presence of synovial plicae in the
      radiocapitellar joint must be considered in the differential diagnosis of painful
      snapping elbow. Arthroscopy confirms the diagnosis and allows excision of the
      plica.

PMID- 11337716
TI  - Roentgenographic assessment of acromial morphology using supraspinatus outlet
      radiographs.
AB  - PURPOSE: The purpose of this study was to offer objective and standardized
      criteria for classifying acromial morphology. TYPE OF STUDY: Blinded study.
      METHODS: Two of the authors independently classified 106 supraspinatus outlet
      radiographs (SOR), obtained from 100 skeletally mature patients with impingement
      syndrome of the shoulder, using both Bigliani's and Park's standardized criteria.
      The same authors classified the 106 SOR again using the same criteria 2 weeks
      later. In addition, 2 orthopaedic residents independently classified the same SOR
      on the basis of the Bigliani and Park criteria in the same manner. RESULTS: The
      rate of agreement was 66.0% (70 of 106) on the basis of Bigliani's criteria and
      95.3% (101 of 106) on the basis of Park's criteria. The interobserver reliability
      coefficient of the 2 authors the first time was 0.448 (poor) and 0.914 (good to
      excellent). Their mean intraobserver reliability coefficient was 0.834 (good to
      excellent) and 0.87 (good to excellent) each. For the 2 orthopaedic residents,
      the rate of agreement was 58.5% (62 of 106) on the basis of Bigliani's criteria
      and 86.8% (92 of 106) on the basis of Park's criteria, and the interobserver
      reliability coefficient the first time was 0.28 (poor) and 0.77 (good to
      excellent) each. The mean intraobserver reliability coefficient was 0.738 (fair)
      and 0.844 (good to excellent) each. CONCLUSIONS: In conclusion, regarding the
      classification for acromial morphology, Park's standardized criteria were far
      more objective, reliable, and reproducible rather than Bigliani's criteria
      through naked eye observations, especially for distinguishing the type II and
      type III acromion.

PMID- 11337717
TI  - International Section: Cuba. Introduction.

PMID- 11337718
TI  - Endoscopic quadricepsplasty: A new surgical technique.
AB  - We present a new surgical subperiosteal endoscopic technique for the release of
      fibrosis of the quadriceps to the femur caused by gunshot injuries, postsurgical
      scarring, and fractures, that was developed at the Arthroscopy Group at Hospital
      Hermanos Ameijeiras in Havana, Cuba. The technique used is a proximal endoscopic
      subperiosteal extension of the usual arthroscopic intra-articular release of
      adhesions, using periosteal elevators and arthroscopic scissors placed through
      medial and lateral superior knee portals to release adhesions and bands of scar
      tissue beneath the quadriceps mechanism. The technique was used in a prospective
      case series of 26 male patients aged 19 to 22 years between February 1997 and
      March 1998 who presented with clinically and ultrasonically documented extra
      articular fibrosis resulting in ankylosis of the knee in extension. Only patients
      who had reached a plateau in their aggressive physiotherapy program with no
      further progression in knee flexion for 3 months were selected. Those with joint
      instability, motion-limiting articular surface pathology, and muscle or
      neurologic injury were excluded. All patients had obtained satisfactory results
      at 2-year follow-up. The extra-articular release gained at final follow-up was
      between 30 degrees and 90 degrees of flexion in addition to that obtained at the
      completion of the standard intra-articular release. Complications included 1 case
      of deep vein thrombosis, 2 cases of scrotal edema, 5 cases of hemarthrosis, and 2
      cases of reflex sympathetic dystrophy. We have found this technique useful in
      obtaining additional flexion and improved function in a difficult class of
      patients with ankylosis caused by extra-articular fibrosis of the quadriceps to
      the femur, allowing immediate aggressive rehabilitation and presenting a useful
      outpatient alternative with fewer and less severe complications than described
      with the classic open Thompson's quadricepsplasty.

PMID- 11337719
TI  - Minimally invasive selective osteotomy of the knee: A new surgical technique.
AB  - We present a simple surgical technique created by the authors to address
      degenerative chondral lesions of the knee and its application in a limited
      prospective case series. The technique assumes the concept of beneficial
      epiphyseal changes caused by disruption of the subchondral bone in improving
      symptoms, as with drilling, microfracture, periarticular osteotomy, and other
      invasive procedures. Minimally invasive selective osteotomy (MISO) is an
      expansion of the arthroscopic treatment of the knee, specifically targeting
      symptomatic lesions with minimal additional trauma and cost, while avoiding
      disruption of the articular surface of the subchondral bone. The technique
      involves a mimimal access approach with selective saw cuts placed with a 1-cm
      oscillating blade parallel to the joint surface 1 to 1.5 cm deep to identified
      lesions. The technique does not address malalignment but can address lesions not
      addressed by classic osteotomies and, as such, may be combined with other
      corrective alignment procedures as necessary. We present the results of MISO of
      the knee in a case series of 62 outpatients carried out at the Orthopaedic
      Division of the Clinical and Surgical Hermanos Ameijeiras Hospital in Havana,
      Cuba. At 2-year follow-up, there was improvement of symptoms without significant
      complications.

PMID- 11337720
TI  - Endoscopic treatment of calcaneal spur syndrome: A comprehensive technique.
AB  - We describe a comprehensive approach to the endoscopic treatment of calcaneal
      spur syndrome developed by the Arthroscopic Group of the Orthopedic Service of
      Hospital Hermanos Ameijeiras in Havana, Cuba. The surgical technique involves
      treatment of the heel spur and plantar fasciitis commonly found in calcaneal spur
      syndrome, but it also addresses adjacent calcaneal periostitis and allows
      decompression of the nerve to the abductor digiti quinti. Medial endoscopy and
      lateral instrumentation are used in a sequential approach with exposure and
      debridement of the posterior roof of the calcaneal arch, followed by removal of
      the calcaneal spur, lateral to medial release of the medial 75% of the plantar
      fascia, and if necessary, debridement of the calcaneal tuberosity periosteum.
      This technique was used in a prospective case series from June 1997 to May 1998
      to treat a select group of 38 feet in 30 patients who reported unacceptable
      levels of pain despite 5 months of conservative treatment, which included an
      aggressive 8-week physical therapy program prescribed by the treating physician.
      Good to excellent results were obtained at 3 months postoperatively in all
      patients with regard to pain relief and return to normal activity, although 5
      patients required a short course of physical therapy to resolve symptoms brought
      on by sports, trauma, or impact loading before 1-year follow-up, at which time
      all patients reported good to excellent results. Complications included 3
      superficial wound infections cured by oral antibiotics and 2 transient lateral
      paresthesias that resolved with rest and nonsteroidal inflammatory medications.
      The described technique may provide a useful method for treating refractory heel
      spur syndrome and warrants further study.

PMID- 11337721
TI  - Arthroscopic decompressive medial release of the varus arthritic knee: Expanding
      the functional envelope.
AB  - We present the rationale and technique for treating medial knee osteoarthritis by
      dynamically unloading the medial compartment of the knee. Recent advances in
      kinematic studies indicate a dynamic linkage between differing degrees of freedom
      in the knee joint. Both the adduction moment and the foot progression angle are
      important determinants of medial compartment loading. The medially osteoarthritic
      knee has progressive compromise of free motion in more than 1 plane. Arthroscopic
      decompressive medial release unloads the medial compartment by release of the
      medial capsule and medial collateral ligament in the presence of intact cruciate
      ligaments, which may allow a decreased adduction moment and decrease of the
      external rotation restraint in extension found in more severely osteoarthritic
      knees. A case series of 38 patients with medial gonarthrosis was treated by this
      technique at the Hermanos Ameijeiras Hospital in Havana, Cuba. All patients had
      good results without postoperative valgus instability or significant
      complications. We feel that this technique warrants further clinical and
      biomechanical study for its use in isolation or in combination with high tibial
      osteotomy or minimally invasive selective osteotomy for the treatment of medial
      gonarthrosis of the knee. A minimally invasive, selective approach to
      biomechanical factors in osteoarthritis may be combined with other modulating
      techniques in efforts to forestall or prevent the need for total joint
      replacement.

PMID- 11337722
TI  - Combined partial arthroscopic synovectomy and radiation therapy for diffuse
      pigmented villonodular synovitis of the knee.
AB  - We present the results of combined partial arthroscopic synovectomy and low-dose
      external-beam radiation therapy (RT) in the treatment of diffuse pigmented
      villonodular synovitis (PVNS) of the knee. Mechanical synovectomy is an effective
      tool in treating PVNS of the knee, but when used alone it may be insufficient to
      eliminate all affected tissue. Intra-articular radiation or external-beam
      radiation may be added to mechanical synovectomy to treat recurrence but is not
      routinely done at the time of initial synovectomy. Combining intra-articular
      synovectomy with RT at the initial treatment for PVNS of the knee may reduce the
      recurrence rate. We present a prospective study of the treatment of 22 patients
      with clinical, ultrasonic, and histologically confirmed findings of diffuse PVNS
      of the knee. Characteristic clinical findings included pain, swelling, and
      erythema. These patients were treated by the Arthroscopic Surgery Group of the
      Orthopaedic Service at the Hospital "Hermanos Ameijeiras" in Havana, Cuba from
      1990 to 1998. The protocol included anterior (patellofemoral, medial, and
      lateral) arthroscopic synovectomy and postoperative RT with a total dose of 2,600
      cGy. This combination therapy was effective in reducing symptoms of pain and
      edema, and in improving overall function of patients. Nineteen patients (86%) had
      good or excellent results at an average follow-up of 33 months (range, 26 to 76
      months). Three patients had residual stiffness and swelling, 2 of whom also had
      pain. Three had clinically and ultrasonically confirmed recurrence of disease and
      were treated with repeat arthroscopic synovectomy without harmful effects from
      RT. In all of the cases requiring repeat arthroscopic synovectomy, we observed
      fibrous bands secondary to reorganization of synovial inflamed tissue, meniscal
      retraction, and microscopic findings of fibrosis and cellular paucity. Partial
      arthroscopic synovectomy combined with low-dose RT in anti-inflammatory doses
      produced good results in the treatment of PVNS without significant complications
      in our patient series. Partial arthroscopic synovectomy of the knee for PVNS may
      be combined with RT to reduce the risk of disease recurrence. Adjuvant RT should
      also be considered for patients receiving a radical synovectomy to treat
      inaccessible or hidden disease sites. Rates of recurrence with combined partial
      (anterior) synovectomy and RT approach that of complete synovectomy in this
      series. Combining RT with radical arthroscopic synovectomy might further reduce
      recurrence rates.

PMID- 11337723
TI  - Severin Nordentoft: The first arthroscopist.
AB  - SUMMARY: We present a recently discovered paper that witnesses to arthroscopic
      activity before World War I. The Proceedings of the 4lst Congress of the German
      Society of Surgeons at Berlin in 1912, contain a presentation entitled "Endoscopy
      of Closed Cavities by the Means of My Trokart-Endoscope." The author was a Danish
      surgeon from Aarhus named Severin Nordentoft. Dr. Nordentoft had constructed an
      endoscope similar to the Jacobaeus thoracoscope, consisting of a trocar 5 mm in
      diameter, a fluid valve, and an optic tube. In addition to suprapubic cystoscopy
      and laparoscopy, he advised the use of such an endoscopic device in the knee
      joint, especially for early detection of meniscal lesions. He baptized the
      procedure "arthroscopy" and gave a vivid and credible description of the handling
      of the instrument, and the view of the anterior region of the knee, including the
      articular cartilage, synovial lining, villi, and plicae. He used sterile saline
      as the optical medium. Unfortunately, he did not express clearly if he performed
      arthroscopy on patients or on cadaver knees. This is the only known paper or
      presentation by Severin Nordentoft on the topic of arthroscopy. In the following
      years, his interests changed to radiotherapy, and today Danish radiologists
      remember him as a pioneer in x-ray treatment of mammary carcinoma and brain
      tumors. Although his pioneering work in arthroscopy was overlooked, the primacy
      of this procedure must now be attributed to him.

PMID- 11337724
TI  - Arch type pathologic suprapatellar plica.
AB  - The authors encountered a case of arch type pathologic suprapatellar plica that
      was excised using an arthroscopic technique. It is reported with a review of the
      literature.

PMID- 11337725
TI  - Arthroscopic treatment of an intra-articular lipoma of the knee joint.
AB  - Intra-articular lipoma is an exceedingly rare diagnosis. There have been less
      than 15 documented cases of an intra-articular lipoma of the knee joint. This
      report presents the first description of an intra-articular knee lipoma treated
      entirely by arthroscopic methods. Preoperative history, examination, and imaging
      studies are reviewed. Intraoperative findings, treatment, and postoperative
      evaluation are discussed as well. Symptomatic intra-articular lipoma of the knee
      joint can be successfully treated by arthroscopic resection. Differentiating
      intra-articular lipoma from lipoma arborescens, a similar but more common
      condition, is important with regards to optimal treatment.

PMID- 11337726
TI  - Pitfalls associated with fixation of osteochondritis dissecans fragments using
      bioabsorbable screws.
AB  - The purpose of this study was to evaluate 2 cases in which bioabsorbable screw
      fixation for an osteochondritis dissecans lesion of the femoral condyle resulted
      in complications necessitating the need for secondary surgery. We reviewed the
      case history of these patients and described the circumstances under which the
      bioabsorbable screws were used, the events leading to the need for secondary
      surgery, and the ultimate outcome. In the 2 cases presented, these implants were
      found to retain their mechanical stiffness for many months. This resulted in
      articular damage in 1 case after the treated lesion failed to heal. In the second
      case, screw breakage 8 months after implantation resulted in it becoming a loose
      body, which required removal during a second arthroscopic procedure. We conclude
      that these implants retain their mechanical properties for many months and cannot
      be relied on to degrade quickly. If a treated lesion fails to heal, these
      implants can cause mechanical problems due to their retained structural
      properties.

PMID- 11337727
TI  - Arthroscopic anterior cruciate ligament reconstruction with quadriceps tendon
      composite autograft.
AB  - At present, no single graft option clearly outperforms another. Autografts
      (patellar tendon, hamstring) and allografts (Achilles tendon, patellar tendon)
      are the grafts most often used. However, each grafts has advantages and
      disadvantages. Quadriceps tendon graft for anterior cruciate ligament
      reconstruction is not new, but an alternative composite graft is introduced here
      that consists of quadriceps tendon-patellar bone and bone obtained from a coring
      reamer used to create the tibial tunnel. This composite graft retains reduced
      morbidity while allowing the secure bone-to-bone fixation associated with bone
      patellar tendon-bone graft.

PMID- 11337728
TI  - Lateral collateral ligament reconstruction using quadriceps tendon-patellar bone
      autograft with bioscrew fixation.
AB  - The lateral collateral ligament is the primary stabilizer against varus stress
      and is also an important contributor in maintaining posterolateral knee
      stability. Quadriceps tendon-patellar bone autograft has been used for anterior
      or posterior cruciate ligament reconstruction. We introduce a reconstructive
      procedure to restore the lateral collateral ligament using a quadriceps tendon
      patellar bone autograft. The procedure is designed for unstable knees with
      concomitant cruciate ligament tear and posterolateral complex injury. This is a
      reasonable choice especially when allograft tissue is not available or in
      patients who are not suited for the use of bone-patellar tendon-bone autograft.

PMID- 11337729
TI  - An all-arthroscopic soft-tissue balancing technique for lateral patellar
      instability.
AB  - Patellar realignment procedures for lateral patellar instability often involve
      open approaches to imbricate the medial soft tissues. We present a technique to
      balance the soft tissues to correct lateral patellar instability that is
      performed entirely arthroscopically. A retinacular release is performed laterally
      and the soft tissues are imbricated medially using arthroscopic suture passing
      and knot tying techniques.

PMID- 11337730
TI  - Arthroscopic reconstruction for acromioclavicular joint dislocation.
AB  - We describe an arthroscopic reconstruction technique for acromioclavicular joint
      dislocation. Subsequent to Baum's first repair of the coracoclavicular complex in
      1886, over 60 operative procedures have been described in the literature. This
      procedure is the first described arthroscopic approach used in reconstruction for
      acromioclavicular dislocation. It provides an anatomically correct and
      structurally sound reconstruction of the coracoclavicular ligament complex. This
      arthroscopic technique is also a cosmetically pleasing alternative to previously
      described open procedures for reconstruction of acromioclavicular joint
      dislocations. As with most arthroscopic procedures, this technique achieves its
      goals with minimal morbidity and violation of the surrounding soft tissues.

PMID- 11337733
TI  - Imaging systems in minimally invasive surgery.
AB  - The imaging system is the eye of the laparoscopic surgeon. The success or failure
      of a minimally invasive procedure depends on the quality and working order of the
      imaging system used. The components that work together to produce an image on the
      monitor is called the imaging chain. The image displayed will be good as the
      chain's weakest component. Understanding how the pieces of this process work
      together will allow the surgeon to troubleshoot basic system problems, leading to
      improved image displays and safer operating environments. Continuous refinement
      of laparoscopes, lighting systems, cameras, monitors, and displays lead to an
      ever-improving operating environment.

PMID- 11337734
TI  - Perceptual aspects of two-dimensional and stereoscopic display techniques in
      endoscopic surgery: review and current problems.
AB  - The aim of this review is to analyze the perceptual aspects of endoscopic imaging
      systems. After discussing depth perception in natural settings, the problems of
      perceiving depth in 2-dimensional representations are investigated. We discuss
      the impact of stereoscopic video systems on the cerebral perceptual system,
      emphasising the fact that despite the addition of binocular disparity
      information, existing stereoscopic video systems are still different from normal
      3-dimensional vision. Both 2-dimensional and stereoscopic video systems require a
      rescaling of visual information to guide motor behavior. A review of the growing
      number of papers comparing 2-dimensional and stereoscopic video systems shows
      that only about 50% of investigators found a significant benefit for stereoscopic
      systems. It is unlikely that image display technology for endoscopic surgery can
      ever progress to the stage where it is equivalent to normal vision. Within this
      limitation, progress will result from a multidisciplinary approach, involving
      technological advances in the quality of the displayed image together with
      psychovisuomotor and ergonomics research, which facilitates the cerebral
      rescaling and perception process by the endoscopic surgeon.

PMID- 11337735
TI  - In situ ablation of hepatic tumors.
AB  - The various technologies and approaches for in situ ablation of hepatic tumors
      are reviewed and the relative merits discussed. The reported experience, though
      limited, is encouraging but the technology is still maturing. At present in situ
      ablation ought to be restricted to patients with inoperable disease, unless
      patients are recruited into randomized trials comparing in situ ablation with
      hepatic surgical resection in specific patient groups. Emerging technologies such
      as gene therapy and electro/sonoporation will also impact on how we best manage
      patients with malignant hepatic tumors. It seems improbable that any one modality
      will prevail on efficacy, and a more likely scenario for future therapy may well
      be a combination multimodal approach tailored to the individual patient and the
      biological characteristics of the tumor.

PMID- 11337736
TI  - Laparoscopic dissecting instruments.
AB  - The authors provide an overview of laparoscopic dissecting instruments and
      discuss early development, surgical options, and special features. End effectors
      of different shapes and functions are described. A comparison of available energy
      sources for laparoscopic instruments includes discussion of thermal dissection,
      ultrasonic dissection, and water-jet dissection. The ergonomic risks and
      challenges inherent in the use of current laparoscopic instruments are outlined,
      as well as ergonomic issues for the design of future instruments. New directions
      that laparoscopic instrumentation may take are considered in connection with
      developing technology in robotics, haptic feedback, and MicroElectroMechanical
      Systems.

PMID- 11337737
TI  - Abdominal wall lift systems in laparoscopic surgery: gasless and low-pressure
      systems.
AB  - Positive pressure pneumoperitoneum (12 mm Hg) is associated with adverse
      physiologic effects that can prove detrimental to certain high-risk patients with
      diminished cardiorespiratory reserve. Mechanical abdominal wall lift (AWL) has
      been proposed as an alternative method of exposure in laparoscopic surgery to
      obviate or minimize these adverse physiologic effects, the risk of CO(2) embolism
      in trauma patients, and tumor dissemination in patients undergoing laparoscopic
      surgery for cancer. This article reviews the systems available for AWL, the
      clinical applications of the technique, and the findings of the randomized
      controlled trials that compare AWL with conventional pneumoperitoneum. AWL
      systems do appear to reduce the adverse cardiovascular and respiratory effects,
      but they do so at the expense of surgical exposure, which is less optimal than
      that provided by the positive-pressure pneumoperitoneum. This reduced exposure
      increases the execution difficulty of the operation and, hence, the operating
      times. This problem is overcome by combination of AWL with low-pressure (3 to 4
      mm Hg) pneumoperitoneum. This combination provides good surgical exposure without
      adverse cardiovascular consequences.

PMID- 11337738
TI  - Tissue adhesives in endosurgery.
AB  - Usage of tissue adhesives/glues for tissue approximation and hemostasis is
      increasing as the related technology advances. There is no accepted
      classification, but surgical adhesives fall into 3 main categories: biological,
      synthetic, and genetically engineered polymer protein glues. Nonresorbable glues
      should be confined only to surface application, such as closure of the wound
      edges. Adhesives for internal use, including hemostasis, tissue edge
      approximation, mesh hernioplasties, sealing of cerebrospinal fluid (CSF) fluid
      and intestinal leaks, and anastomoses, should be biocompatible and resorbable. In
      time, tissue glues and soldering will likely replace, in whole or in part, the
      use of sutures and staples for a variety of tissue approximation surgical
      procedures.

PMID- 11337739
TI  - Laparoscopic instrumentation: Linear cutters, clip appliers, and staplers.
AB  - Some of the most common forms of instrumentation and technology used
      laparoscopically include linear cutters, clip appliers, and staplers. The clip
      applier was the instrument that finally allowed the surgeon to be able to perform
      laparoscopic cholecystectomies. Staplers were developed quickly thereafter for
      tacking tissue together or for applying mesh for hernia repairs. Linear cutters
      became much more useful when the laparoscopic procedures became more advanced,
      and their application continues to expand. This report reviews the technology
      regarding these instruments and discusses clip appliers, linear cutter-staplers,
      and hernia staplers, which are currently available on the market. However, it
      should be noted that there remains a lack of peer-reviewed literature regarding
      the efficiency, efficacy, and cost of these instruments compared with that of
      laparoscopic suturing and knot tying.

PMID- 11337740
TI  - High intensity ultrasound.
AB  - High-intensity focused ultrasound (HIFU) is a technique that was first
      investigated in the 1940s as a method of destroying selective regions within the
      brain in neuro-surgical An ultrasound beam can be brought to a tight focus at a
      distance from its source, and if sufficient energy is concentrated within the
      focus, the cells lying within this focal volume are killed, whereas those lying
      elsewhere are spared. This is a noninvasive method of producing selective and
      trackless tissue destruction in deep seated targets in the body, without damage
      to overlying tissues. This field, known both as HIFU and focused ultrasound
      surgery (FUS), is reviewed in this article.

PMID- 11337741
TI  - Craniofacial anthropometric analysis in patients with 22q11 microdeletion.
AB  - Microdeletions in the 22q11 region are associated with a wide range of
      overlapping phenotypes. The main manifestations of the syndrome include palatal
      anomalies such as cleft palate or velopharyngeal insufficiency, conotruncal heart
      defects, hypocalcemia, immune disorders, and minor facial anomalies. Because of
      the wide variability, facial changes appear to be the most constant manifestation
      of the syndrome and characteristic for informed physicians. The purpose of this
      study is to report the preliminary results of a detailed analysis of
      anthropometric data (35 measurements) in 15 patients (7 females and 8 males
      between 5 and 38 years of age, all white Europeans) with a 22q11 microdeletion.
      Objective anthropometric study showed that 19 measurements and 7 indexes were
      significantly different between 22q11 patients and normative database. The
      typical face showed a short forehead with an anterior vertical excess.
      Downslanting eyes and large binocular width were the most common anomalies in the
      orbital area. The nose showed anomalies with a large root, a short tip, and a
      narrow alar base. There was a narrowing of the mouth and thin lips. Ears were
      small and slightly disharmonic for the children. Statistical comparison between
      children (10 cases) and adults (5 cases) showed that craniofacial assessment was
      more demonstrative in children than in adults.

PMID- 11337742
TI  - Combined immunodeficiency, chromosomal instability, and postnatal growth
      deficiency in a Japanese girl.
AB  - We report on an 11-year-old Japanese girl with combined immunodeficiency and
      chromosomal instability. She had postnatal growth deficiency and microcephaly,
      preaxial polydactyly of the left hand, and susceptibility to infections.
      Immunological studies showed marked lymphocytopenia (around 500/ll), reduced
      lymphocyte response to various mitogens, and reduced or absent serum IgA, IgG,
      and IgM. Cell biological studies of her primary skin fibroblasts demonstrated
      spontaneous chromosome aberrations and radiation hypersensitivity. The
      combination of immunodeficiency, chromosomal instability, and radiation
      hypersensitivity as seen in the girl is present in both ataxia-telangiectasia and
      Nijmegen breakage syndrome. Ataxia-telangiectasia was excluded because of
      differences in clinical features and laboratory data. Likewise, Nijmegen breakage
      syndrome is unlikely to be the case because the characteristic face,
      hyperpigmented spots, and mental retardation present in the syndrome were missing
      in the girl. Sequence analysis of a Nijmegen breakage syndrome responsible gene,
      NBS1, revealed no mutations. A normal NBS1 product was also demonstrated by
      immunoblot analysis using an anti-NBS1 antibody. We propose that the disorder in
      the girl represents a new combination of combined immunodeficiency and
      chromosomal instability.

PMID- 11337743
TI  - Chromosome 2q duplications: case report of a de novo interstitial duplication and
      review of the literature.
AB  - A patient with dir dup 2(q37.1q33.1) is described. Literature review of
      chromosome 2q duplications suggests a consistent, though nonspecific, facial
      phenotype. Segregation of those cases that are "pure" duplications from those
      with accompanying monosomy for another chromosome suggests that a cleft palate
      may not be attributable to the duplicated segment.

PMID- 11337744
TI  - Maternal homozygosity for the common MTHFR mutation as a potential risk factor
      for offspring with limb defects.
AB  - A common mutation, C677T, in the 5,10-methylenetetrahydrofolate reductase (MTHFR)
      gene leads to altered homocysteine metabolism, and has been associated with the
      occurrence of neural tube defects (NTD). Administration of folic acid decreases
      this risk. There is also evidence that periconceptional supplementation of
      mothers with folic acid can decrease the risk of limb defects in the offspring.
      Here we describe a child with a transverse terminal defect of one hand, whose
      mother is homozygous for the C677T MTHFR mutation. We suggest that homozygosity
      for the MTHFR mutation may be a risk factor for transverse terminal limb defect/s
      by an effect mediated through altered folate and homocysteine metabolism. Further
      studies of mothers of infants with limb reduction defects for the MTHFR mutation
      may be of help in establishing this association. A simple intervention in the
      form of folic acid supplementation would be protective, should an association be
      established.

PMID- 11337745
TI  - Genetically determined low maternal serum dopamine beta-hydroxylase levels and
      the etiology of autism spectrum disorders.
AB  - Autism, a neurodevelopmental disability characterized by repetitive stereopathies
      and deficits in reciprocal social interaction and communication, has a strong
      genetic basis. Since previous findings showed that some families with autistic
      children have a low level of serum dopamine beta-hydroxylase (DbetaH), which
      catalyzes the conversion of dopamine to norepinephrine, we examined the DBH gene
      as a candidate locus in families with two or more children with autism spectrum
      disorder using the affected sib-pair method. DBH alleles are defined by a
      polymorphic AC repeat and the presence/absence (DBH+/DBH-) of a 19-bp sequence
      118 bp downstream in the 5' flanking region of the gene. There was no increased
      concordance for DBH alleles in affected siblings, but the mothers had a higher
      frequency of alleles containing the 19-bp deletion (DBH-), compared to an
      ethnically similar Canadian comparison group (chi(2) = 4.20, df = 1, P = 0.02 for
      all multiplex mothers; chi(2) = 4.71, df = 1, P < 0.02 for mothers with only
      affected sons). Although the odds ratios suggested only a moderate relevance for
      the DBH- allele as a risk allele, the attributable risk was high (42%),
      indicating that this allele is an important factor in determining the risk for
      having a child with autism. DBH genotypes also differed significantly among
      mothers and controls, with 37% of mothers with two affected sons having two DBH-
      alleles, compared to 19% of controls (chi(2) = 5.81, df = 2, P = 0.03). DbetaH
      enzyme activity was lower in mothers of autistic children than in controls (mean
      was 23.20 +/- 15.35 iU/liter for mothers vs. 33.14 +/- 21.39 iU/liter for
      controls; t = - 1.749, df = 46, P = 0.044). The DBH- allele was associated with
      lower mean serum DbetaH enzyme activity (nondeletion homozygotes: 41.02 +/- 24.34
      iU/liter; heterozygotes: 32.07 +/- 18.10 iU/liter; and deletion homozygotes:
      22.31 +/- 13.48 iU/liter; F = 5.217, df = 2, P = 0.007) in a pooled sample of
      mothers and controls. Taken together, these findings suggest that lowered
      maternal serum DbetaH activity results in a suboptimal uterine environment
      (decreased norepinephrine relative to dopamine), which, in conjunction with
      genotypic susceptibility of the fetus, results in autism spectrum disorder in
      some families.

PMID- 11337746
TI  - "Baby rattle" pelvis dysplasia.
AB  - We report an apparently previously undescribed lethal skeletal dysplasia,
      clinically resembling achondrogenesis, but with distinct radiologic and chondro
      osseous morphologic features. These comprise bifid distal ends of the long bones
      of the limbs, absent vertebral body ossification, a unique "baby rattle" pelvic
      configuration with tall and broad ilia, absent endochondral ossification, regions
      of mesenchymal cells within the resting cartilage, and abnormal mesenchymal
      ossification.

PMID- 11337747
TI  - Characterization of ARHGEF6, a guanine nucleotide exchange factor for Rho GTPases
      and a candidate gene for X-linked mental retardation: mutation screening in
      Borjeson-Forssman-Lehmann syndrome and MRX27.
AB  - Borjeson-Forssman-Lehmann syndrome (BFLS) is a syndromic X-linked mental
      retardation that has been mapped by linkage to Xq26-q27. A nonsyndromic mental
      retardation family, MRX27, has also been localized to a region of the X
      chromosome overlapping Xq26-q27. The gene for ARHGEF6 (also known as alphaPIX or
      Cool-2), a newly identified guanine nucleotide exchange factor, was identified as
      a potential candidate XLMR gene, due to its location within the BFLS and MRX27
      critical regions and its function in the regulation of PAK3 (a known MRX gene).
      The full coding sequence and genomic structure of the gene for ARHGEF6 was
      established in silico, based on available genomic, EST, and cDNA sequence
      information. Mutation analysis in BFLS- and MRX27-affected individuals was
      carried out. No mutations were found in two BFLS families or MRX27. Although
      ARHGEF6 is unlikely to be the gene responsible for either BFLS or MRX27, it
      remains a prime candidate for nonspecific or syndromic mental retardation linked
      to Xq26.

PMID- 11337748
TI  - New syndrome of mental retardation, Robin sequence, and brachydactyly.
AB  - We report on two sibs, brother and sister, affected with a multiple congenital
      anomalies/mental retardation (MCA/MR) syndrome, characterized by mild to moderate
      psychomotor delay, Robin sequence, peculiar facial appearance, and brachydactyly.
      To our knowledge, this combination of anomalies has not been reported previously.
      The occurrence of a similar pattern of anomalies in brother and sister suggests
      autosomal recessive inheritance; however, dominant transmission with reduced
      penetrance cannot be ruled out in our patients, since minor clinical signs, such
      as brachydactyly, are also present in the father.

PMID- 11337749
TI  - Two Thai families with Norrie disease (ND): association of two novel missense
      mutations with severe ND phenotype, seizures, and a manifesting carrier.
AB  - We describe two Thai families with Norrie disease (ND) in three generations,
      including 10 affected males and one manifesting female. All affected males in
      each family had severely defective eye development with complete loss of vision.
      In addition, three male patients (one from family 1 and two from family 2)
      suffered from epilepsy, and one female carrier from one family manifested
      blindness with phthisis bulbi in her right eye. Mutation analysis of the ND gene
      (NDP) revealed two different novel missense mutations (L16P and S75P) that co
      segregated with ND in each family, suggesting that the newly appearing proline at
      codon 16 or codon 75 alters the conformation of the ND protein and contributes to
      the severe phenotype of ND in each family. Other studies suggest that epileptic
      seizures or growth retardation that is associated with ND is the consequence of
      loss of contiguous genes, because most such patients had deletions extending
      beyond the Norrie locus. Our finding that the three affected males in the two
      families with the missense mutations had epilepsy does not support a contiguous
      gene effect, but favors the pleiotropism of NDP, at least as far as the epileptic
      manifestation is concerned. The unilateral blindness in the female carrier may
      have been due to non-random X-inactivation.

PMID- 11337750
TI  - De novo duplication (5)(q31.3q33.3): report of a patient and characterization of
      the duplicated region using microdissection and FISH.
AB  - We report on a 2-year-old boy presenting with growth and psychomotor retardation
      and facial anomalies, including a flat face with prominent forehead, a flat nasal
      bridge and flat occiput, unusually long curved eyelashes, and a thin upper lip
      with down-turned corners of the mouth. Analysis of GTG-banded chromosomes
      demonstrated that the patient had extra chromosomal material in the long arm of
      one chromosome 5. This chromosome aberration was characterized further using
      microdissection and FISH with band-specific probes and a de novo direct
      duplication (5)(q31.3q33.3) was shown to be present. We have compared this case
      with others known to be partially trisomic for chromosome 5q reported in the
      literature.

PMID- 11337751
TI  - Linkage mapping of a nonspecific form of X-linked mental retardation (MRX53) in a
      large Pakistani family.
AB  - Nonspecific X-linked mental retardation is a nonprogressive, genetically
      heterogeneous condition that affects cognitive function in the absence of other
      distinctive clinical manifestations. We report here linkage data on a large
      Pakistani family affected by a form of X-linked nonspecific mental retardation. X
      chromosome genotyping of family members and linkage analysis allowed the
      identification of a new disease locus, MRX53. The defined critical region spans
      approximately 15 cM between DXS1210 and DXS1047 in Xq22.2-26. A LOD score value
      of 3.34 at no recombination was obtained with markers DXS1072 and DXS8081.

PMID- 11337752
TI  - Chimeric creatures in Greek mythology and reflections in science.
AB  - "The Chimaera" in Homer's Iliad, "was of divine stock, not of men, in the
      forepart a lion, in the hinder a serpent, and in the midst a goat, ellipsis
      Bellerophon slew her, trusting in the signs of the gods." In Hesiod's Theogony it
      is emphasized that "Chimaera ellipsis had three heads, one of a grim-eyed lion,
      another of a goat, and another of a snakeellipsis". In addition to this
      interspecies animal chimera, human/animal chimeras are referred to in Greek
      mythology, preeminent among them the Centaurs and the Minotaur. The Centaurs, as
      horse/men, first appear in Geometric and early Archaic art, but in the literature
      not until early in the fifth century B.C. The bullheaded-man Minotaur, who is not
      certainly attested in the literary evidence until circa 500 B.C., first appears
      in art about 650 B.C. Attempts, in the fourth century B.C. and thereafter, to
      rationalize their mythical appearance were in vain; their chimeric nature
      retained its fascinating and archetypal form over the centuries. Early in the
      1980s, experimental sheep/goat chimeras were produced removing the reproductive
      barrier between these two animal species. Late in the 1990s, legal, political,
      ethical, and moral fights loomed over a patent bid on human/animal chimeras.
      Chimeric technology is recently developed; however, the concept of chimerism has
      existed in literary and artistic form in ancient mythology. This is yet another
      example where art and literature precede scientific research and development.

PMID- 11337753
TI  - Popliteal pterygium and multiple pterygium syndromes.

PMID- 11337754
TI  - Reported tandem duplication/deletion of 9q is actually an inverted duplication.

PMID- 11337755
TI  - Ascribe the simplest interpretation.

PMID- 11337756
TI  - Prader-Willi syndrome due to maternal uniparental disomy of chromosome 15 in a
      boy with a balanced 3;21 translocation.

PMID- 11337757
TI  - [Teaching-welfare integration: a case study].
AB  - The teaching-welfare integration process (TWI) between the "Escola de Enfermagem
      da Universidade Federal do Rio Grande do Sul" and the "Hospital de Clinicas de
      Porto Alegre" is this work's object of study focusing the actors in it and its
      concrete historical practice. The intention is that of knowing the dynamics of
      the process relationships, understanding it is a collective work as the result of
      historical and social changing. The inter-institutional dichotomy becomes evident
      as a rule, unleashing an integration issue. The existing TWI is not a concordant
      one but its integrating power connections must be used as a motive for its action
      and transformation, defining the making and re/making of new alternatives.

PMID- 11337758
TI  - [Intramuscular administration of drugs: skills of pharmacy personnel].
AB  - Complications from the incorrect administration of intramuscular injections can
      cause serious organic damages, infections and increase the patient's permanence
      in health institution or to harm the functions in the work. The previous study
      detected several cases of patients with local complications after administration
      of diclofenac in pharmacies and it concluded that the lack of knowledge of this
      technique can be the causes of these complications. This current study objectives
      to identify and evaluate the level of knowledge of the professional that
      administer medications in pharmacies of Ribeirao Preto--SP. The study constituted
      in a survey, from a questionnaire with 20 open and closed questions, applied to a
      population constituted for occupational working in pharmacies, selected through
      the method of the sampling, resulting in a total of 41 pharmacies. It was
      concluded that the population is receiving medications from occupationals,
      without a specific formation and with deficit of knowledge regarding the
      technique. The subjects referred not to receive training to exercise that
      procedure, learning it with other employee or observing somebody that
      accomplishes it. It results knowledge gaps that can cause complications in the
      population that uses the services of those institutions.

PMID- 11337759
TI  - [Daily living with hypertension: changes, restrictions and reactions].
AB  - Aiming to describe daily living of hypertensive people after Arterial
      Hypertension (AH) diagnoses and to identify changes in their lives. The method of
      inquiry used was descriptive and qualitative using discursive method to figure
      out theme factors. The results showed different behaviors/reactions of being sick
      according to their daily living after discovering AH, that not always happened at
      the same time that the antihypertensive treatment began. Those differences seems
      to be associated with individual understanding of sickness itself and of impact
      in their lives. So, getting along with hypertension is to learn about the
      sickness and symptoms and also make the necessary changes.

PMID- 11337760
TI  - [Nursing diagnosis of the patient in the immediate postoperative period].
AB  - The aim of this study was to identify the nursing diagnoses that are more
      frequent in patients in immediate post-operative period. Data were collected and
      recorded on specially cards, through evaluation of 28 patients in the first two
      hours after the admission of the patient. The nursing diagnoses were set by one
      of the authors, based on Taxonomy I, proposed by North American Nursing Diagnosis
      Association--NANDA. The diagnoses that occurred mostly were: Risk for injury
      (100.0%), Risk for infection (92.8%), Sensory perceptual alterations (89.2%),
      Risk for aspiration (82.1%), Impaired physical mobility (71.4%), Impaired tissue
      integrity (82.1%) and Hypothermia (67.8%).

PMID- 11337761
TI  - [Moving and lifting patients: postural and ergonomic aspects].
AB  - The most dangerous and difficult tasks faced by health workers are those
      procedures involved with lifting and moving patients. Therefore, training and
      recycling programs in lifting procedures are a compulsory part of programs for
      the prevention of musculoskeletal disorders in schools and health institutions.
      The present study presents basic and innovative orientation with an ergonomic
      approach regarding these procedures, together with the use of devices.

PMID- 11337762
TI  - [Perception of nurses about risk factors for nosocomial infection].
AB  - A study was undertaken in a pediatric teaching hospital to evaluate the nurses
      understanding about risk factors for nosocomial infections. The data were
      obtained in interviews with nurses of the emergency room, intensive and semi
      intensive units. The analysis of the meaning of the conversation permitted the
      identification of the following risk factors: inadequacy of the hospital design
      and construction, deficiency of care equipment and supplies, understaffing, lack
      of education and training to the healthcare workers and orientation to the
      patients family.

PMID- 11337763
TI  - [Surgical scrub: evaluation of its adequacy for the prevention of biological
      risks in surgical procedures II: effectiveness of surgical scrub].
AB  - The study elaborated evaluation patterns of the components of the surgical scrub
      in hospitals of the district of Sao Paulo. The most important difficulty was the
      lack of rules and consent on the types of the fabrics, as a microbiological and
      contact with blood and other fluids barrier. However, it was possible to identify
      positive and problematic aspects. It was observed that the components are similar
      among the hospitals, considering the design and the way of fabrics production.
      Gloves were the ones with the best quality results, while shootweares were the
      worst. The most problematic aspect was referred to the acquisition controls and
      the re-use process of the components.

PMID- 11337764
TI  - [A large-scale project: a current pedagogic proposal].
AB  - This study discourses about a nursing project, the well known "Larga Escala
      Project", its history, the legislation that gives support to it and its
      trajectory in the Health Secretary of the Township of Sao Paulo. The conclusion
      is that the "Larga Escala Project" is a valid pedagogic proposal and it must be
      encouraged and amplified to all the national field.

PMID- 11337765
TI  - [Experiencing a difficult and revealing passage with her hospitalized child--a
      live-in mother's experience].
AB  - This study was conducted with live-in mother in university hospital. The
      objectives were as follows: to understand the experienced interactions, to
      identify the meanings that a family attribute to the experience of going through
      the child's hospitalization, to identify what the experience of hospitalization
      provokes in the family life and construct a model theory representative of the
      experience. Reference Theory the Symbolic Interactionism and Reference
      Methodology Grounded Theory had been utilized. From results appeared the
      phenomenon Going in search of solution and Going through a difficult situation.
      Through these phenomena, the main category Experiencing a difficult and revealing
      passage with her child was identified.

PMID- 11337766
TI  - [Communication between nurses' aides and patients with chronic renal failure].
AB  - This article makes considerations about the communication in the nursing
      assistance to the chronic renal patient, submitted to hemodialysis, which
      treatment is characterized by a frequent relation and sometimes a "closed"
      professional relation between nurse and patient. The object of this article is to
      analyse and give examples of the way to use consciently the verbal and nonverbal
      communication in order to establish a therapeutic interaction of these patients.

PMID- 11337767
TI  - [Management of public health services: relation to experience].
AB  - This study has as objective to discuss technologies in use in administration of
      public health's services. The empiric data which this analysis it sketches are
      based in a professional experience of one of the authors as technical adviser
      close to Government Bureau of Health of Sao Paulo. The practice of management
      experienced is confronted with proposals of managerial technology brought by
      MERHY; ONOCKO (1997) and articulated to strategies of construction of full
      subjects starting from the work. The conclusions indicate the need to rethink the
      managerial technologies in use and they aim new managerial instruments.

PMID- 11337768
TI  - [Clinical experience of nursing students: transition of identities].
AB  - The purpose of this article is to describe nursing students clinical experience
      in the Maternal-Child and Psychiatric Nursing Department of the School of Nursing
      of the University of Sao Paulo (EEUSP). This activity has been implemented since
      1996, not only to follow the demands of the Minimum Curriculum in Nursing, but
      also to give consistency to one of the purposes of the new curriculum of the
      EEUSP. This new purpose is concentrates on the facilitation of the transition
      process from being a student to being professional. The authors describe the
      experience of those involved in the process-Undergraduate student, faculty
      members and nurses making some considerations, regarding the results that
      demonstrate development of autonomy and responsibility in the future
      professional.

PMID- 11337769
TI  - [Breast-feeding: a necessary change in focus].
AB  - During many years, the objective of the scientific production on breast-feeding
      has been the product: milk. However, researches during the 90.s, performed by
      nurses, have shown that this focus is iatrogenic: milk becoming more important
      than people (the mothers in this case) and that the fortresses must be seen as
      persons who are breastfeeding (or trying to do so). The breast-feeding process
      can be very painful, also causing premature weaning. The author proposes, in view
      of these considerations, care that is centered on the person of the fortress. It
      must also be remembered that the fortress needs adequate social-ambient
      surroundings to achieve breast-feeding and it is society's duty to provide them.

PMID- 11337770
TI  - [Effectiveness of tuberculosis vaccines].
AB  - BCG revaccination in the Sverdlovsk Region is performed thrice: at the age of 5,
      10 and 15 years. The percent of children covered by tuberculin diagnosis and BCG
      vaccination is growing. Complications of BCG vaccination remain at the same
      level. Tuberculosis morbidity in children rises due to minor forms of
      tuberculosis. However, it is 2 times less than mean tuberculosis incidence in
      Russia. Primary infection is registered 4.5 times less frequently.

PMID- 11337771
TI  - [Tuberculin sensitivity in infants and preschool children].
AB  - Marked fluctuations in sensitivity to tuberculin related to the time of
      nonspecific vaccinations were found in children aged 1 to 7 years vaccinated with
      BCG within the first week of life in annual Mantoux test (2 tuberculin units). At
      the age of 3 and 7 years vaccinations raise sensitivity to tuberculin causing a
      rise in positive reactions to tuberculin. This indicates changes in
      postvaccination allergy to BCG.

PMID- 11337772
TI  - [Computerized tomography of the lungs and mediastinum in children with
      tuberculosis risk].
AB  - Computed tomography (CT) was made in 75 children and adolescents infected with M.
      tuberculosis. As shown by x-ray, they had normal lungs and mediastinum. The
      children comprised a group of tuberculosis risk and had undergone regular check
      ups for tuberculosis. CT has detected tuberculosis of the intrathoracic lymph
      nodes (ITLN) in 28(37.3%) children. Adenopathies were discovered in 8 anatomic
      groups, being more frequent in retrocaval, tracheobronchial, pulmonary and
      paratracheal. 25 children were diagnosed to have minor form of ITLN tuberculosis
      (nodes size 6-10 mm), 3 children had more prominent adenopathy up to 20 mm in
      diameter. Three groups of preventive policy are identified: with minor
      tuberculosis of ITLN, intrathoracic micropolyadenopathy and normal CT picture of
      the lungs and mediastinum.

PMID- 11337773
TI  - [Strategy of the management of children with lesions of intrathoracic lymph nodes
      during the calcinosis phase].
AB  - To verify the diagnosis of tuberculosis of the intrathoracic lymph nodes
      (paraaortal group) in calcination phase in hospital setting using tuberculin
      diagnosis, tomography, immunological and serological tests, clinical examination,
      epidemiological history, 70 children aged 3-15 years were examined. It was found
      that 58.6% of the children had 2-3 signs of tuberculosis activity. Therefore,
      they need 6-month antituberculous treatment in the sanatorium. 35.7% had no signs
      of active tuberculosis and can be followed up outpatiently. 5.7% exhibited more
      than 5 signs of tuberculosis activity and must be treated basically for 8-10
      months in hospital.

PMID- 11337774
TI  - [New cases of tuberculosis of respiratory organs during phases of reverse
      development in children].
AB  - Out of 313 preschool children treated in a specialized children's hospital for
      local tuberculosis, 23.6% of cases were first diagnosed in phases of reverse
      development. 12.8% of children cured spontaneously. Local activation as
      infiltration of intrathoracic lymph nodes and dissemination to the lungs and
      other organs occurred in 8.1 cases. The activation was seen both in children with
      spontaneously cured tuberculosis and those after chemoprophylaxis. It is
      concluded that all the children with newly detected tuberculosis in reverse
      phase, irrespective of previous chemoprophylaxis, should be treated in hospital
      with subsequent observation of the phthisiologist.

PMID- 11337775
TI  - [Experience in chemotherapy of tuberculosis in children based on WHO
      recommendations].
AB  - WHO recommends that patients with primary intrathoracic tuberculosis fall into 4
      categories by clinical symptoms, severity and spread of the process. They are to
      receive 2 staged treatment. The duration of each chemotherapy phase depends on
      the time of reverse development of the specific process regarding abacillarity of
      the primary tuberculosis by clinicoroentgenological dynamics. Therapy in children
      is completed after a full resolution of the pathological changes or upon
      stabilization of the process at the stage of residual changes when clinical
      laboratory evidence indicates absence of latent activity of the process.
      According to these WHO criteria 255 children aged 3 to 12 years were treated in
      the Central Research Institute of Tuberculosis for the last 10 years.

PMID- 11337776
TI  - [Approaches to combined therapy of pulmonary tuberculosis in adolescents
      excreting drug-resistant Mycobacterium tuberculosis].
AB  - The data are presented on 138 adolescents with active, advanced tuberculosis. M.
      tuberculosis were detected in the sputum and bronchial lavage of 75(54.3%)
      adolescents. 32 patients had M. tuberculosis resistant to drugs. 28 untreated
      patients demonstrated primary drug resistance (37.5%). Intensive combined
      treatment with consideration of bacterial resistance, administration of reserve
      drugs, wide spectrum medicines bring about positive results, but in patients with
      drug resistance positive dynamics is slow.

PMID- 11337777
TI  - [State of children's health at the end of the 20th and the beginning of the 21st
      centuries: problems and solutions].

PMID- 11337778
TI  - [Rapidly progressing forms of pulmonary tuberculosis in adolescents].
AB  - Examination of 23 adolescents with rapidly progressive pulmonary tuberculosis
      (RPPT) discovered severe bilateral lesions in 47.8%, caverns in 91.3%, M.
      tuberculosis in 86.9% of the examinees. 75% of the adolescents were resistant to
      antituberculous treatment. RPPT in adolescents is represented mainly by
      infiltration pulmonary tuberculosis (78.3%), caseous pneumonia and disseminated
      pulmonary tuberculosis (21.7%). RPPT develops because of late diagnosis and
      infection with drug-resistant M. tuberculosis.

PMID- 11337779
TI  - [Tuberculous meningitis in infants].
AB  - Tuberculous meningitis (TM) develops more frequently in unvaccinated or
      inadequately vaccinated infants (28 cases of 34), in contact infants (26 of 34
      cases). Within the first year of life TM is especially aggressive. Late diagnosis
      and treatment leave significant residual neurological changes or result in lethal
      outcomes.

PMID- 11337780
TI  - [Tuberculin sensitivity in children at the time of diagnosis of tuberculosis of
      intrathoracic lymph nodes].
AB  - Trends in RM with 2 TU PPD-L were analysed in 71 children at the time of
      detection of tuberculosis of intrathoracic lymph nodes (TITLN). The disease is
      often diagnosed in children getting infected with tuberculosis infection.
      Monotonous tuberculin tests represent the most frequent variant of tuberculin
      allergy at the time of TITLN diagnosis in children. Careful follow-up of children
      with monotonous RM (2 TU) may improve TITLN outcomes.

PMID- 11337781
TI  - [Immunological reactivity in adolescents with different manifestations of
      tuberculosis infection].
AB  - Immunological reactivity was investigated in 306 tuberculosis adolescents aged 13
      18 years: 117 with a turn of the tuberculin reactions, 20 with tuberculosis
      running for more than 2 years in the presence of aggravating factors, 57 with
      active tuberculosis of the respiratory organs, 15 with attenuating active
      tuberculosis, 36 with clinically cured tuberculosis. 79 noninfected adolescents
      served control. Immunological reactivity was altered more appreciably and often
      (nonspecific declined but specific enhanced) in active tuberculosis, less
      significantly in cured tuberculosis. The least changes occurred in the turn of
      tuberculin reactions and in patients infected for more than 2 years. Cellular
      immunity underwent most pronounced changes.

PMID- 11337782
TI  - [Diagnostic significance of immunity indices in children with local forms of
      primary tuberculosis].
AB  - 195 children with tuberculosis and 25 healthy controls were examined to define
      diagnostic value of immunological indices. Measurements were made of IgA, IgM,
      IgG, CIC, LMIR, EIA at admission and at the edge of tuberculin sensitivity. EIA
      and LMIR were positive more frequently in children with active tuberculosis, in
      aggravated course and at the edge of tuberculin sensitivity. Evaluation of
      immunity, EIA and LMIR is diagnostically significant especially at the edge of
      tuberculin sensitivity.

PMID- 11337783
TI  - [The significance of polymerase chain reaction in diagnosing causes of
      subfebrility in children and adolescents].
AB  - Examination of 37 children and adolescents with long-term subfebrility and other
      manifestations of intoxication without local pathological changes included blood
      test (polymerase chain reaction) for M. tuberculosis. Tuberculous bacteriemia was
      discovered in 16(43.2%) cases. Non-acute onset and long-lasting intoxication,
      rejection of other reasons, tuberculin sensitivity, reduction or disappearance of
      the intoxication in antituberculous treatment, negative results of repeated PCR
      for M-tuberculosis gave grounds to suspect active tuberculosis in 13 children of
      16. Clinical and x-ray picture corresponded to tuberculous intoxication in
      children and adolescents.

PMID- 11337784
TI  - [Ultrasonic diagnosis of tuberculosis of major joints in children and
      adolescents].
AB  - Results of ultrasonic echotomography (UET) are available for 42 patients with
      affection of major joints. Provocation with tuberculin (20 TU) was made. UET data
      before and 3-5 days after the provocative test were compared. Reactive
      inflammation at the site of tuberculosis-affected joint caused by the provocation
      test was reflected by UET. This method detected early tuberculous lesion of the
      joints in 34 examinees.

PMID- 11337785
TI  - [Endoscopic ventriculocisternostomy in the treatment of complications of
      tuberculous meningoencephalitis in an infant].

PMID- 11337786
TI  - [80 years of the use of BCG vaccine].

PMID- 11337787
TI  - [New tuberculosis vaccine: dream or reality?].

PMID- 11337788
TI  - [20-year results of the research at the adolescent department of the Central
      Research Institute of Tuberculosis].

PMID- 11337789
TI  - [Treatment of tuberculosis in children and adolescents].

PMID- 11337790
TI  - [Relations between epidemiology and epizootiology of tuberculosis (comments on
      the article by V.A. Krasnov and G.S. Murashkina, published in "Problemy
      tuberkuleza", 1998, No.5, pp. 8-11)].

PMID- 11337791
TI  - [Antituberculosis care of children and adolescents in tuberculosis risk groups].
AB  - Because of deterioration of epidemiological situation by tuberculosis,
      individuals from tuberculous infection foci and social risk group require special
      care. It is important to integrate efforts of phthisiatric and general
      therapeutic and prophylactic services in detection of tuberculosis in children
      and adolescents, to create controlled conditions for conduction of
      antituberculous measures.

PMID- 11337792
TI  - [Caring for patients with AIDS].
AB  - This study presents the results of a research conducted with 27 health
      professionals caring for patients with aids on the isolation ward of a Regional
      Reference Center of aids. Data were analyzed and interpreted according to the
      Existential Phenomenology and demonstrate the view of professionals regarding to
      this type of caring for. This is a tough, demanding and discriminated patient who
      should be seen just like any other patient; the fear of contagion and prejudice
      interfere in the deliver of care and in the relationship with this patient,
      damaging the professional attitude. Although the deleterious effects of the
      isolation ward on patients are perceived, there are no signs of any perspectives
      of offering effective support to these patients. The results of the research
      suggest the need of introducing educational and supporting programs to
      professionals of this area.

PMID- 11337793
TI  - [Surgical scrub: evaluation of its adequacy in preventing biological risks in
      surgery: I. Its use in surgery].
AB  - The study elaborated approaches for adequate use of the surgical scrub and it
      evaluated, through systematized observation, the performance of the surgical team
      during the surgery. The adopted procedure was very valid, allowing to recognize
      positive and problematic aspects. Except the protecting glasses, all the other
      components of the surgical scrub were used. The subject located in the use form,
      where caps and masks were more problematic among anaesthesists and circulate
      nurses; apron and gloves among surgeons and, mainly, scrub nurses.

PMID- 11337794
TI  - [Errors in drug administration: knowledge diffusion and identification of the
      patients as important aspects].
AB  - The administration of medications is a multi-system process. Errors can happen in
      all the stages of that process. Strategies can be used and it should be published
      to minimize the occurrence of errors. This study had the following objectives: to
      identify and to analyze publications with themes about the administration of
      medication in nursing, hospital and pharmacy journals and to verify the
      identification in the bed and in the patients' forearm in impatient clinics. To
      reach the first objective it was realized a revision of the literature in three
      journals of larger national circulation of the described areas, in the period
      from 1987 to 1997. The identified articles were classified in 5 types: nursing
      staff, teaching, medications, research and technique. It was identified 19
      articles on the thematic studied, being 42.1% of these related to the technical
      aspects of the administration of medications. To reach the second objective it
      was taken an investigation of one day, chosen accidentally, being verified the
      identification of the beds and the patients in the 360 beds of the institution.
      Of these, 74.7% were busy and 75.8% properly identified. It was observed that
      23.8% of the patients have gotten bracelet of placed identification, in the day
      previous to the surgery and not in the moment of the hospitalization. The results
      evidenced the need to increase the publication of the studies about errors and to
      increase actions that minimize the occurrence of errors in the medication in
      impatient patients.

PMID- 11337795
TI  - [Evaluation of the body posture of nursing personnel when moving patients in
      bed].
AB  - The patients' movement in bed, is a procedure that demand great physical effort
      and use of good corporal mechanics for the nursing personnel, relative of
      preventing them back pain problems. Recognizing the importance of the movement
      and positioning, to promote safety and comfort to the patient, and before the
      professionals' complaints, described in the literature, this work has for
      objectives: to identify and analyzer the postures assumed by the nursing workers
      and identify the means and difficulties found during the execution of the
      referred activity. Through the technique of direct observation they were filmed,
      through videotapes, thirty procedures of patient's movement in the bed executed
      by nursing workers of an orthopedic clinic of an university hospital. The results
      evidence that the thirty procedures were executed along 197.41 minutes and that
      the corporal postures more frequently assumed they were, in respect to back, arms
      and legs, back inclined/arms with elbow down of row of seats/legs extension
      (53.76%). In agreement with the beginnings of the corporal mechanics and of the
      ergonomics, such postures are considered painful to the man, due to the muscle
      skeletal aggressions and to the physical overload that they cart. The workers
      aimed the aspects little space (58.82%), physical load (52.94%) and absence of
      the personal (47.06%), as the main difficulties found in the execution of
      patient's movement in the bed, corroborating with the discoveries of the
      literature, characterizing that activity as painful. They pointed: the adequate
      technique (36.29%), used of sheet (35.29%) and space adequate (23.52%), as
      aspects that would facilitate the execution of the procedure.

PMID- 11337796
TI  - [The problem of suffering: perception by adolescents with cancer].
AB  - Adolescents with cancer undergo suffering resulting from diagnosis, therapy and
      changes in their routine and family life. The objective of this study was to
      identify the chief causes of their suffering, identified in interviews with those
      patients themselves. The study population were 12 adolescents admitted to the
      Paediatric Clinic of the Ribeirao Preto Medical School Clinical Hospital,
      University of Sao Paulo, from the 13th. November, 1997 to 16th. December, 1997.
      Data were analysed by means of qualitative approach. The chief causes of
      suffering reported by the studied adolescents were: hospitalization, restrictions
      in routine activities, aggressive therapy, modification of self-image and fear of
      dying. The adolescents not only talked about their suffering but also offered
      some suggestions to lessen it, as for instance, use of central venous catheter,
      liberation of visiting time, reducing number of hospitalization events, efficient
      communication and good rapport with the attending team.

PMID- 11337798
TI  - [Conceptual framework for ostomy care in the hospitalized adult patient].
AB  - The author points out a brief revision of the legal, ethical and scientific bases
      of the ostomy care process and describes some important topics about caring the
      ostomist in the different operatory phases.

PMID- 11337797
TI  - [Suggestions for stress relieve at the workplace: opinion of postgraduate
      nurses].
AB  - The work overload, relationship and communication problems, institution's
      characteristics and ambiental pollution were the stressing organization agents
      with the greatest punctuation in this study composed by 30 nurses. The work
      planning, work humanization, suitable human resources, improving communication
      and continued education were the suggestions given by nurses to minimize these
      stressing organizational agents. Analysing the stressing extra organizational
      agents, economic and familiar problems, work distance and transportation to work,
      were the most pointed.

PMID- 11337799
TI  - [Occupational mobility: expression of this process in nursing].
AB  - This exploratory and descriptive study presents the family context socioeconomic
      and cultural advancements in addition to emphasizing the educational trajectory
      of a group of nurses whose the common characteristic is their previous formation
      in the Nursing area. Based in the original study which provided part of the data
      used for this study, the analytical approach was of either of quantitative and
      qualitative nature as a consequence of the duplicate focus used in these data
      treatment viewing their complementarity. The present study was intended to
      characterize the studied population emphasizing the socioeconomic and cultural
      aspects which were determinant to the peculiar habitus, and culminated with a
      socioeconomic classification carried out either previous and subsequently to
      graduation time in order to detect the social mobility phenomenon resulting from
      the occupational mobility. It was then concluded that the latter could be
      observed in more than half the studied population, mostly because of the double
      employment linkage than the professional advancement itself.

PMID- 11337800
TI  - [Chronic pain and depression: study of 92 patients].
AB  - Was examined the influence of depression in the occurrence and pain intensity.
      Patients presenting advanced cancer (n = 92) were evaluated. The patients were
      divided in 2 groups, with or without pain during the week preceding the
      interview. Pain and depression were evaluated. Pain was observed in 62.0% of the
      cases and lasted 10 months as an average. It was moderate in the majority of
      patients and severe in 1/5 of them. Depression was related with the presence and
      intensity of pain. Patients with pain presented higher depression scores than
      patients without pain (p < 0.05). Higher pain scores were also correlated with
      higher depressive scores (p < 0.05).

PMID- 11337802
TI  - [The meaning of child and family care in the community: the learning experience
      of nursing students].
AB  - This present study, by applying qualitative research under a phenomenological
      perspective, attempts to seek an understanding of the meaning of the learning
      experiences of nursing students who care for child and family in the community.
      The data have been obtained through individual open interviews with nine
      students. Two themes have emerged from the analysis of the data: FACING
      CHALLENGES and GENERATING A NEW VIEW. Applying the theoretical approach of Viktor
      Frankl's existential analysis allows us to understand that what mobilizes
      students when facing challenges is the search for knowledge and desire to do
      something. Moreover, this study allows a reflection about significant learning in
      nursing, generating a new view as a consequence to the student feelings, thoughts
      and actions in the promotion of the personal and professional growth.

PMID- 11337801
TI  - [The historicity of the interpretative theories about health and disease].
AB  - The interpretative theories of the health-illness process that can be identified
      through History have as consequence intervention projects upon the reality, in
      response to social needs. Until the 19 century, they could be synthesized in two
      main streams: ontologic and dynamic. In the ontologic conception, illness assumes
      the character of a natural or supernatural entity, external to the human body,
      that shows itself when invading it. The dynamic conception sees illness as a
      product of the disharmony among vital forces, and the re-establishment of the
      health comes of the restoration of this balance. At the end of the 18 century,
      the social-environmental paradigms prevailed in Europe as forms of explanation
      for human illness, linked to the dynamic conception, and the first evidences of
      the social determination of the health-illness process were formulated. The onset
      of the Bacteriologic Era made the ontologic conception victorious and its
      conquests led to the abandon of the social approaches to face the populations
      health problems. At the present time, one can identify the prevalence of the
      multicausal theory, with emphasis in the individual conditionings. This paper
      proposes the articulation of the individual and collective dimensions of the
      health-illness process, in consonance with the Theory of Nursing Praxical
      Intervention in Collective Health.

PMID- 11337803
TI  - [Accompanying the patient to the hospital: meaning and perception].
AB  - The study was performed within the phenomenological referendum following the
      modality of situated phenomenon in order to understand the experience of being
      the hospitalized adult patient's accompany. The phenomenological analysis of 8
      speeches led to 4 themes: "The Approach", "The Accompany", "The Feelings" and
      "The Changes in the Family' and Personal's Life". The purposes reveal the
      accompany, to be with the patient rises from the need to help him/her with
      physical limitation or dependence; give care, gratitude; give emotional support;
      transmit enthusiasm and optimism; identify and fulfill his/her needs; favor the
      communication; observe and verify the assistance rendered and follow his/her
      clinical evolution. The accompany was permeated by the preoccupation and
      generated upsets all family.

PMID- 11337804
TI  - [Counter-reference and reference system organization in the health system
      context: perception of nurses].
AB  - This study aimed to understand and to care counter-reference and reference system
      upon the context of the Health System in Botucatu-SP, Brazil from the nurses who
      experience this practice. We adopted a qualitative research, situated fenomena
      model, methodologically derived from phenomenology. In the first part of this
      study there is a brief presentation record about the Health System in Brazil
      contextualizing as it follows counter-reference and reference system. Results
      were obtained through ideographic analysis and nomothetic analysis from the
      testimony of 13 nurses interviewed, bringing 13 themes, reduced into 3
      categories: counter-reference and reference system operation, guiding
      possibilities and local system structural factors. This study showed that this
      purpose is still an horizont that depend's the isolately professional liability.

PMID- 11337805
TI  - [Proposal for a survey for assisting the family and caregivers of patients with
      spinal cord injuries].
AB  - This study proposes a basis survey for assistance to the family and caregivers
      because we believe there is necessity of family participation on the treatment,
      trying to understand and share the disease or deficiency situation. We
      objectified to sketch the relationship degree and the people's gender that
      accompanied the spinal cord injured hurt medular patient in nursing consultations
      and to discuss the necessity of basis survey to the assistance family and to the
      caregiver. 101 nursing consultations were accomplished, in clinic health, to the
      spinal cord injured patient and his/her relative and 36 patients were totalized,
      from this number 26 (72.22%) were male and 10 (27.78%), were female. It was
      verified that the men with medular lesion, in the greater number (27-80.7 O/o),
      were accompanied with his relatives specially mother and wife, while the women
      with medular lesion, in the greater number too (7-70%) were accompanied with her
      relatives of diversified proximity. In reference to the basis survey that
      comprehend the care at house and the caregiver necessity, we can affirm its
      relevance, trying to context the family support identified attending the
      caregivers.

PMID- 11337806
TI  - [Reflections on the teaching to undergraduate nurses about group dynamics].
AB  - The present article aims at reflecting on the experience of the authors about the
      nursing undergraduate teaching on group dynamics, that began in 1992. Authors
      focus nursing and the works with groups; the structure, content and development
      of this specific course.

PMID- 11337807
TI  - [The otherness as a criterion of bioethics].
AB  - The present paper proposes questions about otherness as a fundamental criterion
      of Ethics and Bioethics, focusing on health care. The referencial mark used is
      the concept of otherness based on the Existencial Phenomenology.

PMID- 11337808
TI  - [Sexuality according to Michel Foucault: a contribution to nursing].
AB  - The author develops a reflexion about Foucault conception in relation to the
      "sexuality dispositive" that has been presented in the book "Microfisica do
      Poder". She tries to rescue, through this classic literature, a historic and
      social point of view in the practice of nursing, without missing the actual
      concepts that deppreciate the affection of the personal relations to overvalue
      the masculine virility, converting the pleasure a consumer goods and a goal in
      itself.

PMID- 11337809
TI  - [Playing in hospital: addition to nursing care].
AB  - Playing is one of the essential activities for the physical, emotional and social
      development to the child. Although the recognized importance of this activity,
      during the hospitalization process it is little value, so it is not find out
      between the foreseen therapeutic actions that are preview. The goal of this paper
      is discuss the theory and practice principles to subsidize the utilization of
      play in the aid to the hospitalization children. The empiric data collection was
      realized through the participant observation of 11 children who were intern in a
      pediatric unit of a teaching hospital of State of Sao Paulo up country. We
      identify that the act to play has repercussions in the child, nurse and hospital.
      To the child it is not obstruct the development; help it in the understanding
      about what is occurring with itself and discharge fear, tension, anxiety and
      frustration; promote satisfaction, funny and spontaneity and allows it transforms
      experiences that should support inactive in active discharge. To the nurse it is
      a tool of intervention and a way of communication, that allows detect the
      uniqueness of each child. Related to the hospital, change the current view that
      is only a pain and suffering place.

PMID- 11337810
TI  - [Aging and the elderly in the undergraduate nursing courses in Brazil: from the
      current situation to a proposal for the content of the program].
AB  - The teaching nursing undergraduate was verified in 77 courses in Brazil about
      elderly's attention, hourly load and time of insert of this content in the
      curriculum. The authors suggest fundamental themes to the nurses' formation to
      act with elderly in the different contexts in their health's attention.

PMID- 11337811
TI  - [Graduation from nursing: learning about the Brazilian psychiatric reform].
AB  - This paper aims at identifying the changes that became part of the teaching of
      psychiatric nursing. The study points out the concern regarding teaching updating
      in this area in which the teacher's transformation, participation and the
      creation of a new concept about psychiatric knowledge and practice make it
      possible to have new ways to learn how to learn the brazilian psychiatric reform.

PMID- 11337812
TI  - [The year 2030: dawn of the millennium of the profession: nursing--a prospective
      view of nursing undergraduate students].
AB  - Study based on testament-letters written by freshmen students of the
      undergraduate course in Nursing, who should imagine to be in the year 2030.
      Everything imagined by these students and that might have happened in the three
      earlier decades was the subject of this study, such as professional and nurses
      achievements, outbreak of cure for illnesses, social prestige and positions.

PMID- 11337813
TI  - [Being a mother affected with AIDS: reliving the original sin].
AB  - This study aimed to understand the meaning of being with AIDS among HIV/AIDS
      mothers. It looks for to identify the emotions and the way of cope with the
      situation as a mother has a healthy son. This study was conducted based on the
      Social Representations Theory. The findings showed "to be mother" and "to have
      AIDS" represented as a process that does not finish in the disease itself. Also
      it was found that there is a polarize link between the good and the evil. Indeed,
      this study brought the sexuality likewise the polarized link, being AIDS linked
      to evil aspect. These women from this study had perceived themselves as guilty of
      something, as a result, they deserved the punishment that the AIDS imposed on
      them.

PMID- 11337814
TI  - [Nursing care of patients with bipolar disorder and feelings of the student
      nurse: study of a case].
AB  - This paper is report of an experience, while graduation student during the
      Psychiatric Nursing Discipline, where I accompanied a patient carrier of Bipolar
      Disorder of fasting changing. The nurse-patient interaction is very important
      because it is through a good relationship that we a trust entail, capable to help
      the patient in the two different phases, with plans of individualized cares. I
      comment the depressives and maniacs behaviors of the patient in this study and
      the therapeutic techniques used in each phase. My feelings during the interaction
      were analyzed front to the behaviors presented by the patient.

PMID- 11337815
TI  - [Describing the features that characterize the singular status of nursing care:
      the picture and the fact of professional practice].
AB  - The rehearsal reconsiders the institutionalized process of taking care,
      evidencing the own order of that fact mobilized by that interdiction. It
      evidences the effects of that process in the conformation of the identifying the
      professional institutional pact, the framework that gives it support, identifying
      its properties, as well as the possibilities of creating a device of capable work
      to promote finding again a significative primary task.

PMID- 11337816
TI  - Expression of titin in skeletal muscle varies with hind-limb unloading.
AB  - The effects of prolonged hind-limb unloading on titin antibody localization and
      expression of titin isozymes of single fibers from the synergistic slow-twitch
      soleus (SOL) and fast-twitch plantaris (PLN) of adult rats were studied after 14
      and 28 days of hind-limb unloading (HU). Titin antibody localization and
      expression was not altered at 14 days of HU. However, there was a 4% loss in
      antibody to Z-band distance (Ab-Z) in the SOL and an increase of 8% in PLN Ab-Z
      after 28 days of HU. The titin and myosin heavy chain composition of single
      fibers and small bundles of fibers from control and unloaded muscles were
      examined using 2% to 12% sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. There was a marked loss of relative amounts of titin in both SOL
      and PLN following 28 days of HU. As the protein loads for these measures were
      identical, the authors conclude that these findings represent an actual loss of
      titin density rather than a decreased value due to a loss of total muscle mass.
      Laser scanning densitometry of the titin bands show a marked decrease in density
      and molecular weight in unloaded SOL. In the PLN, marked losses of titin density
      were accompanied by decreased electrophoretic motility. The results demonstrate
      that the titin isoform composition and titin antibody localization of skeletal
      muscle is altered during hind-limb unloading. Furthermore, as titin is
      responsible for positional stability of the sarcomere and the fiber during
      contraction, change in isoforms during HU may predispose atrophied muscle to
      injury during reuse and recovery.

PMID- 11337817
TI  - Relationship of skeletal muscle atrophy to functional status: a systematic
      research review.
AB  - In the realm of muscle atrophy research, many studies address minute details of
      molecular function but few examine the effects of atrophy in terms of mobility,
      strength, endurance, and performance of activities of daily living. The
      relationship between impairment and functional limitation is the focus of this
      research review. A wide array of studies constitute this area of inquiry,
      including investigations as diverse and widely disparate as molecular chemistry
      and space travel and populations as different as rats, healthy young men, and
      elderly women. Thirty-four studies were selected based on their fit with the
      Enabling-Disabling Model. Three paradigms of atrophy and function emerged.
      Adaptation reflects the plastic nature of muscle when placed under certain
      conditions, ranging from disuse to high-resistance exercise. Injury/loss
      describes damage to muscle tissue from ischemia, medications, or reloading or
      reperfusion trauma. Also in this category is the loss of muscle that is seen with
      aging. Integrity relates to the muscle's tendency to protect itself and maintain
      structural adjacencies and cellular proportions. Based on the 3 muscle research
      paradigms, the relationship of muscle atrophy to function is portrayed as a
      bidirectional interaction wherein form and function have an influence on each
      other by way of physical changes, including those of adaptation, injury/loss, or
      integrity. A conceptual model is constructed to reflect this relationship.

PMID- 11337818
TI  - Influence of adjuvant chemotherapy on skeletal muscle and fatigue in women with
      breast cancer.
AB  - The purpose of this pilot study was to investigate the changes in skeletal muscle
      size and strength and perception of fatigue in women undergoing adjuvant
      chemotherapy for breast cancer. The findings of this pilot study suggest that
      changes in muscle size and strength can occur during chemotherapy. Quadricep
      muscle size increased for two subjects. These subjects also experienced an
      increase in muscle strength. This is the first known study to address change in
      muscle size and fatigue in women during adjuvant chemotherapy for breast cancer
      from an integrated biobehavioral perspective. Our findings may indicate that
      muscle size can increase during chemotherapy, but this may not diminish the
      subjective experiences of fatigue. As the potential for causing serious damage to
      striated muscle exists, further research into muscle changes and activity during
      chemotherapy and its role in fatigue is crucial.

PMID- 11337819
TI  - Docosahexaenoic acid--induced vasorelaxation in hypertensive rats: mechanisms of
      action.
AB  - The authors investigated the vasorelaxant properties of the omega-3 fatty acid,
      docosahexaenoic (DHA, 22:6n-3), and the possible involvement of endothelium
      derived nitric oxide, prostanoids, opening of K+ channels, and/or modulation of
      calcium-mediated events. Isolated aorta from male spontaneously hypertensive rats
      (SHR) (age 16-17 weeks) were used to measure isometric tension. DHA-induced (1
      100 mumol/l) relaxation was examined following contraction to norepinephrine (NE)
      (10(-6) mol/l) or high-K+ (80 mmol/l) solution in the presence and absence of
      various inhibitors and calcium-containing solution. DHA acid induced a
      significant vasorelaxant effect in both NE and high-K(+)-induced contracted SHR
      aortic rings, although DHA relaxations were greater in high-K(+)-induced
      contracted rings. In the absence of extracellular calcium, DHA (5-30 mumol/l)
      inhibited the initial phasic and sustained components of NE-induced contraction
      under different conditions. Inhibition of nitric oxide synthesis by N omega-nitro
      L-arginine methyl ester hydrochloride (100 mumol/l) had no effect on DHA
      relaxations; however, indomethacin or nifedipine caused significant inhibition at
      > or = 30 mumol/l DHA. The K+ channel blocker, glibenclamide, but not tetraethyl
      ammonium, also had an inhibitory effect on DHA-induced relaxation. These results
      indicate that DHA's vasorelaxant actions in SHR aorta are independent of
      endothelium-derived nitric oxide; however, at DHA concentrations > or = 30
      mumol/l, vasodilatory prostanoids that activate ATP-sensitive K+ channels (KATP)
      may be involved. At lower concentrations, DHA-induced relaxation appears to be
      attributed to modulation of intracellular Ca2+ release and L-type Ca2+ channels
      in vascular smooth muscle cells. The vasorelaxant properties of DHA may
      contribute, in part, to the blood pressure-lowering effect of dietary fish oil in
      this hypertensive model.

PMID- 11337821
TI  - Managing migraine: strategies for successful patient outcomes.
AB  - This article highlights information from the 2000 National Conference for Nurse
      Practitioners symposium held in Washington, D.C., on November 9, 2000. It was
      sponsored by The Nursing Institute of Springhouse Corporation and funded by an
      unrestricted educational grant from Merck & Co., Inc. The firsttopic, "Overview
      of Migraine: Compelling Effects on Patients and Society," was presented for Dedie
      Downey Russell, CNP, ANP/GNP, MS. The second topic, "Understanding
      Pathophysiology: Evolving from Traditional to Current Therapeutic Options," was
      presented by Dara G. Jamieson, MD. Maureen Moriarty-Sheehan, MS, CRNP, who also
      served as chairperson, presented the third topic, "Developing a Management Plan
      for Optimal Patient Benefit."

PMID- 11337820
TI  - Comparison of autonomic nervous system indices based on abdominal pain reports in
      women with irritable bowel syndrome.
AB  - Abdominal pain is an important symptom in irritable bowel syndrome (IBS), but
      patients report typical pain intensities ranging from mild to very severe. In a
      sample of women, the authors sought to determine whether measures of systemic
      autonomic activity are related to self-reported pain intensity and the occurrence
      of pain in the postprandial period. One hundred and six women with IBS and 41
      controls completed bowel symptom and psychological distress questionnaires and
      wore 24-h Holter electrocardiogram monitors to estimate global heart rate
      variability measures of parasympathetic activity and sympathetic nervous
      system/parasympathetic nervous system balance. About one-third of the IBS sample
      reported severe or very severe abdominal pain (n = 34/106), and about one-half of
      the IBS sample reported postprandial pain (n = 52/106). Even after statistically
      controlling for age, body mass index, and psychological distress, vagal heart
      rate variability measures were markedly lower in women reporting high pain (P <
      0.01) and markedly higher in women reporting postprandial pain (P < 0.02). The
      vagal component of heart rate variability appears to be reduced in women with
      severe abdominal pain, especially in those whose pain is not postprandial.

PMID- 11337822
TI  - Exercise and atherogenesis.
AB  - Atherogenesis involves the activation of endothelial cells and the egress of
      atherogenic T lymphocytes and monocytes into the intima. Exercise training
      contributes to the arrest and even reversal of atherosclerosis by modifying risk
      factors and by inducing an atheroprotective phenotype in endothelial cells and T
      cells.

PMID- 11337823
TI  - Corticospinal responses to motor training revealed by transcranial magnetic
      stimulation.
AB  - Transcranial magnetic stimulation was recently used to investigate the nature of
      adaptations that occur in the central nervous system in response to motor
      training. In this report, we provide a brief description of trancranial magnetic
      stimulation and discuss its potential as a tool for identifying corticospinal 
      response to exercise.

PMID- 11337824
TI  - Exercise interventions during cancer treatment: biopsychosocial outcomes.
AB  - More than 1.2 million Americans are diagnosed with cancer each year, and many
      receive intensive medical treatments. Currently, exercise is not considered a
      standard quality-of -life intervention for cancer patients. In this article, 11
      studies are reviewed that have examined exercise interventions concurrent with
      cancer treatment. The key conclusion is that exercise improves a wide range of
      biopsychosocial outcomes in cancer patients, but much more reserch is needed.

PMID- 11337825
TI  - Mechanisms and clinical implications of post-exercise hypotension in humans.
AB  - Post-exercise hypotension is common after moderate-intensity dynamic exercise. It
      results from persistent reductions in vascular resistance mediated by the
      autonomic nervous system and vasodilator substances. These  effects appear more
      pronounced and last longer in hypertensive individuals. Post-exercise hypotension
      may also play an important role in plasma volume recovery after exercise.

PMID- 11337826
TI  - Diaphragm adaptations elicited by severe chronic obstructive pulmonary disease:
      lessons for sports science.
AB  - In humans, the diaphragm adapts to severe chronic obstructive pulmonary disease
      with (a) fast-to-slow transformations of the fiber types and myofibrillar
      proteins and (b) increases in the activity of mitochondrial oxidative enzymes. We
      suggest that progressive endurance training over several decades accounts for
      these adaptations.

PMID- 11337827
TI  - Muscle activation and deactivation dynamics: the governing properties in fast
      cyclical human movement performance?
AB  - Repetitive cyclical motion and intrinsic muscle properties each impose
      constraints on the nervous systems to produce well-coordinated movements. We
      suggest that as cycle frequency increases, activation and deactivation dynamics
      strongly influence the neural control strategy used and may be the governing
      muscle property that limits performance. Pedaling and animal studies provide
      supporting data.

PMID- 11337828
TI  - Excitation-contraction uncoupling: major role in contraction-induced muscle
      injury.
AB  - The mechanisms that account for the strength loss after contraction-induced
      muscle injury remain controversial. We present data showing that (1) most of  
      the early strength loss results from a failure of excitation-contraction coupling
      and (2) a slow loss of contractile protein in the days after injury prolongs the
      recovery time.

PMID- 11337829
TI  - Cardiovascular drift during prolonged exercise: new perspectives.
AB  - We propose that cardiovascular drift, characterized by a progressive decline in
      stroke volume after 10-20 min of exercise, is primarily due to increased heart
      rate rather tahn a progressive increase in cutaneous blood flow as body
      temperature rises.

PMID- 11337830
TI  - Semi-volatile organic compounds in the Campaspe River system (Victoria,
      Australia).
AB  - The levels of semi-volatile organic compounds (SVOCs) in the Campaspe River
      system, North Central Victoria, Australia, were monitored from January to
      September 1995, and the environmental trends and sources of these compounds were
      determined. The land use within particular catchments dictated the complexity of
      the SVOCs in run-off water. Run-off from native forest contained the greatest
      number of SVOCs. Soil and ground litter were shown to contain the greatest
      complexity of SVOCs, mostly terpenes. However, only a small proportion were
      leached by run-off with the remainder being tightly bound to the soil or
      volatilizing to the atmosphere. Under the prevailing drought of early 1995, the
      rivers contained no detectable SVOCs until the first catchment run-off after
      significant rainfall in May. The maximum complexity and concentration of the
      SVOCs coincided with extensive run-off after heavy rainfall in June, effecting a
      surge of SVOCs with the flood peak. Fatty acids, their amides and hydrocarbons
      made up the majority of the compounds identified and were in the 1-39
      micrograms/l concentration range. The levels then diminished as the catchment was
      flushed by continual run-off. These results support Lake's 1967 hypothesis that
      natural floodwaters contain a signature of SVOCs entering from the catchment. The
      downstream passage of these compounds was obstructed by a man-made storage, Lake
      Eppalock, with only low concentrations of SVOCs (1-3 micrograms/l) in the
      outflow, displaying no correlation to run-off.

PMID- 11337831
TI  - Rainfall-induced sediment and pesticide input from orchards into the Lourens
      River, Western Cape, South Africa: importance of a single event.
AB  - Rainfall-induced runoff transported sediments and pesticides into the Lourens
      River and its tributaries during a 28.8-mm rainstorm in mid-December 1998.
      Average 1-h peak levels of current-use insecticides applied to adjacent orchard
      plots were 1.5 micrograms l-1 azinphos-methyl, 0.2 microgram l-1 chlorpyrifos and
      2.9 micrograms l-1 total endosulfan (alpha, beta, S) in the river itself.
      Respective average 1-h pesticide levels associated with suspended particles were
      1247, 924 and 12,082 micrograms kg-1, along with 980 micrograms kg-1 of
      prothiofos. Total suspended solids increased during runoff from 32 to 520 mg l-1.
      The contaminated edge-of-field runoff entered the river via the tributaries
      directly bordering the orchard-growing areas. Increased concentrations of
      azinphos-methyl and prothiofos associated with suspended sediments were
      demonstrated to persist for about 3.5 months without any further input in one of
      the tributaries. This illustrates that the short-term exposure has the potential
      to result in long-term contamination of surface waters. In terms of chemical load
      during the 1-h peak discharge period, the single rainfall event caused a loss of
      173 g h-1 azinphosmethyl, 55 g h-1 chlorpyrifos, 740 g h-1 total endosulfan
      (alpha, beta, S) and 41 g h-1 prothiofos. Levels of contamination were extremely
      high; they exceed the national water quality standards and those established by
      the US EPA. A comparison with standard toxicity data and 24-h LC50 s for the
      local amphipod species Paramelita nigroculus, obtained during this study,
      indicates that the concentrations found in the river may result in acute toxic
      effects on aquatic invertebrates and fishes. A probability analysis of 10-y
      rainfall data revealed that the frequency of a similar storm event occurring
      within the main spraying season is 1.7 y-1.

PMID- 11337832
TI  - Oxidation of metal-diethylenetriaminepentaacetate (DTPA)--complexes during
      drinking water ozonation.
AB  - This study investigates the oxidative transformation of
      diethylenetriaminepentaacetate (DTPA), a synthetic ligand, during drinking water
      ozonation. The rate coefficients for the reactions of CaDTPA3- and ZnDTPA3- with
      ozone were determined to be 6200 and 3500 +/- 150 M-1 s-1, respectively. The
      reactivity of Fe(III)DTPA2- towards ozone was found to be much lower (< 10 M-1 s
      1), but near neutral pH the reactivity of the Fe(III)-complexes is dominated by
      [Fe(III)(OH)]DTPA3-. For the reaction of Fe[(III)(OH)]DTPA3- with ozone a rate
      coefficient of 2.4 +/- 0.2 x 10(5) M-1 s-1 was measured. The rate coefficients of
      the reactions of the ZnDTPA- and Fe(III)DTPA with OH radicals have been
      determined by a competitive method as 2.4 +/- 0.4 x 10(9) and 1.5 +/- 0.1 x 10(9)
      M-1 s-1, respectively at pH = 7. The degradation of low concentrations of DTPA
      complexes during ozonation was investigated in natural waters under drinking
      water relevant conditions. Based on our findings CaDTPA3- and ZnDTPA3- are judged
      as easily degradable. Fe(III)DTPA complexes showed a somewhat lower reactivity,
      but were still typically degraded by one order of magnitude at ozone dosages of
      approximately 20 microM (1 mg L-1) in the three natural waters tested. Molecular
      ozone was found to be the major oxidant for the metal-DTPA complexes during
      ozonation.

PMID- 11337833
TI  - Catalytic dechlorination of chlorophenols in water by palladium/iron.
AB  - Three isomer chlorophenols, o-, m-, p-chlorophenol, were dechlorinated by
      palladium/iron powder in water through catalytic reduction. The dechlorinated
      reaction is believed to take place on the surface site of the catalyst in a
      pseudo-first-order reaction. The reduction product for all the three isomers is
      phenol. The dechlorination rate increases with increase of bulk loading of
      palladium due to the increase of both the surface loading of palladium and the
      total surface area. The molecular structure also has an effect on the
      dechlorination rate. For conditions with 0.048% Pd/Fe, the rate constants are
      0.0215, 0.0155 and 0.0112 min-1 for o-, m-, p-chlorophenol, respectively. Almost
      complete dechlorination is achieved within 5 h.

PMID- 11337834
TI  - Derivatization of the mutagen MX (3-chloro-4(dichloromethyl)-5-hydroxy-2(5H)
      furanone) with butyl alcohols prior to GC-MS analysis.
AB  - An extremely potent mutagen, 3-chloro-4(dichloromethyl)-5-hydroxy-2(5H)-furanone
      (MX) is commonly present in chlorinated drinking water. Due to its high mutagenic
      activity and according to WHO guidelines its concentration should be controlled
      in drinking waters. Determination of MX is difficult due to the low (ppt) levels
      at which the compound usually exists in drinking waters. Results obtained with
      butanols as MX derivatization agents are shown and derivatization with sec
      butanol is presented as a method which significantly lowers GC/MS detection
      levels of MX.

PMID- 11337835
TI  - Denitrification rates in the sediments of Lake Memphremagog, Canada-USA.
AB  - Denitrification is the most important mechanism of nitrogen retention in aquatic
      systems. Research into the spatial variability of sediment denitrification has
      been relatively rare. Here, we use the N2 flux technique to measure sediment
      denitrification rates at 19 littoral and 1 profundal site in Lake Memphremagog.
      Littoral denitrification rates were highly variable with an average rate of 111
      mumol N m-2 h-1. Littoral denitrification rates were positively related to
      temperature (r2 = 0.66, p < 0.01), % organic matter (r2 = 0.31, p < 0.05) and
      macrophyte biomass density and negatively related to depth. These results in
      combination with an analysis of the literature and a predictive model created
      from literature data relating site depth and denitrification rates show that the
      littoral zone dominates whole lake denitrification.

PMID- 11337836
TI  - Nitrification and denitrification as a source for NO and NO2 production in high
      strength wastewater.
AB  - Laboratory and half-technical scale experiments were performed to evaluate nitric
      oxide (NO) and nitrogen dioxide (NO2) production during biological N-elimination
      from wastewater with high ammonium concentration (about 700 mg N L-1). In a
      laboratory scale bioreactor with biomass retention, the ammonia oxidizer
      Nitrosomonas europaea and the denitrifier Paracoccus denitrificans were grown as
      reference organisms in co-culture in order to simulate the nitrifying and
      denitrifying community of wastewater treatment plants. Synthetic wastewater and
      sludge liquor from the municipal wastewater treatment plant in Lueneburg
      (Germany) were used. In the laboratory scale reactor, during the treatment of
      synthetic wastewater, 0.28% of the oxidized ammonium-N was released as NO-N by a
      pure culture of Nitrosomonas. A simultaneously nitrifying and denitrifying co
      culture only released 0.04 to 0.2%. NO2 formation was not observed. NO production
      was much higher in sludge liquor. A pure culture of Nitrosomonas produced 0.52%
      NO + NO2-N (= NOx-N), a co-culture of Nitrosomonas and Paracoccus even 1.64% NOx
      N. The production rate strongly depended on the media and the organisms used. In
      a co-culture of N. europaea and P denitrificans, Nitrosomonas was shown to be the
      most efficient NO producer. NO production increased with ammonium oxidation rate
      and with nitrite concentration of the medium. In synthetic wastewater, NO
      production was not influenced by reduced oxygen content. However, in sludge
      liquor NO production rate increased with decreasing O2 concentration. Here, for
      the first time, the formation of significant amounts of NO2 during simultaneous
      nitrification/denitrification could be demonstrated. In half-technical scale
      experiments, only 0.07% of the oxidized ammonium-N was released as NO-N from the
      nitrification stage. NO2 was not detectable. Release of nitric oxide from the
      denitrification stage was mainly diffusion limited and the amount produced did
      not exceed 0.0001%. A calculation on the basis of the results presented, revealed
      that biological treatment of nitrogen-rich wastewater is not a significant source
      for pollution of the atmosphere with NOx in industrial areas.

PMID- 11337837
TI  - Electrochemical determination of dissolved uranium in Krka River estuary.
AB  - The applicability of the previously developed method for electrochemical
      determination of dissolved uranium concentration has been tested on natural water
      samples taken from the Krka river estuary during various seasons and along
      different depth profiles. The method is based on the following treatment of the
      sample: destroying the uranyl-carbonato complexes by adjusting the pH to 3,
      enabling the formation of adsorbable uranyl-hydroxo complexes by adjusting the pH
      to 6.5-7.0 and measurement by cathodic stripping voltammetry technique. As the
      signal of the dissolved uranium reduction is sometimes masked by the signal of
      the matrix of the sample, a resolution enhancement including digestion and/or
      deconvolution has to be applied. The measured concentration of dissolved uranium
      varies in the range from 0.4 to 3.3 x 10(-8) mol l-1, corresponding to the data
      found in the literature. The depth profile of dissolved uranium concentration
      distributions shows conservative behaviour. The X-ray fluorescence spectroscopy
      (XRF) confirmed the applicability of the method, yet pointing out to its
      limitations caused by the matrix of the solution.

PMID- 11337838
TI  - Simultaneous chromium(VI) reduction and phenol degradation in a fixed-film
      coculture bioreactor: reactor performance.
AB  - Simultaneous Cr(VI) reduction and phenol degradation was observed in a fixed-film
      bioreactor consisting of a coculture of phenol-degrading bacteria, Pseudomonas
      putida DMP-1, and Cr(VI)-reducing bacteria, Escherichia coli ATCC 33456. Near
      complete Cr(VI) reduction and phenol degradation was observed during steady-state
      operation of the reactor under loadings of 5-21 mg Cr(VI) l-1 d-1 and 840-3350 mg
      phenol l-1 d-1. 2-hydroxymuconic semialdehyde (2HMSA), succinate, and acetate
      were the detected steady-state organic acid metabolites which accounted for 13
      23% of TOC in the effluent. Optimum Cr(VI) reduction rate was observed under a
      Cr(VI) loading of approximately 26.5 mg Cr(VI) l-1 d-1 just before system
      overload. System overload was characterized by the increase in effluent Cr(VI)
      and phenol concentrations. System resilience to Cr(VI) toxicity was demonstrated
      by rapid recovery of biological activity and reduced effluent Cr(VI) and phenol
      concentrations after off-loading the system from overloaded conditions.

PMID- 11337839
TI  - Presence of carbamate pesticides in environmental waters from the northwest of
      Mexico: determination by liquid chromatography.
AB  - A study on the presence of carbamate pesticides, namely aldicarb, aldicarb
      sulfoxide, baygon, benthiocarb, carbofuran, 3-hydroxycarbofuran, carbaryl,
      desmedipham, methiocarb, methomyl, thiodicarb, oxamyl, and propham was made in
      ground and surface waters from an agricultural zone of the Yaqui Valley located
      in northwest Mexico. Trace determinations were made by liquid chromatography (LC)
      with post-column fluorescence detection (EPA method 531.1) or LC-diode array UV
      detection coupled on-line to a solid-phase extraction (SPE) system and using a 13
      x 4.6 mm i.d. precolumn and a 150 x 4.6 mm i.d. analytical column, both packed
      with a C18 silica. Results indicated that the level of contamination with
      methiocarb was 5.4 micrograms/L in a groundwater sample and that for 3
      hydroxycarbofuran was 18 micrograms/L in a surface water sample. This study
      provides the basis for a future monitoring program.

PMID- 11337840
TI  - Photodegradation of chlorinated hydrocarbons in the presence and absence of
      dissolved oxygen in water.
AB  - The photodegradation rates of seven chlorinated hydrocarbons; C2Cl4, C2HCl3,
      C2H4Cl2, 1,1,1-C2H3Cl3, 1,1,2-C2H3Cl3, CHCl3, CCl4 were investigated under the UV
      bandwidths of 185 and 254 nm in the presence and absence of dissolved oxygen (DO)
      in water. These hydrocarbons are possible contaminants of groundwater. This study
      confirms that the degradation rates of all chlorinated hydrocarbons are elevated
      in the absence of DO. This was especially apparent for chlorinated methane and
      ethane. Tetrachloroethylene's rate was the highest among the seven hydrocarbons
      regardless of the DO levels. It was clear that the concentration of intermediate
      trichloroethylene produced by photodegradation of tetrachloroethylene in the
      absence of DO was 1/50th of that in the presence of DO. Photodegradation in the
      presence of DO resulted in the formation of O3 and hydroxyl radicals.
      Alternatively, the photodegradation in the absence of DO resulted in the
      formation of organic radicals and a dissociation of the bond. It is discussed
      that DO acts as an "inner filter" or "scavenger" that reduces the UV light
      intensity in the photoreactor. Molecular O2 has absorption bands at 185 and 254
      nm, the former being stronger. The processes of degradation depend on the
      degradation rate relative to the presence and absence of DO.

PMID- 11337841
TI  - Application of microbial enumeration technique to evaluate the occurrence of
      natural bioremediation.
AB  - Natural bioremediation is believed to be the major processes that account for
      both containment of the petroleum-hydrocarbon plume and reduction of the
      contaminant concentrations. In this study, the feasibility of applying the
      microbial enumeration technique was assessed for natural biodegradation
      evaluation at three selected gasoline spill sites. At each site, two monitor
      wells were installed along the groundwater flow, and one multilevel sampler (MLS)
      was installed to delineate the vertical distribution of the contaminant plume.
      Two continuous soil cores were collected at each site to evaluate the horizontal
      distribution of the microbial activity. Soil samples were used for microbial
      enumeration, grain-size distribution analysis, and sediment extraction. In situ
      tracer study was performed using 1,2,4-trimethylbenzene (1,2,4-TMB) as the tracer
      to study the efficiency of contaminant biodegradation. Investigation results
      demonstrate the agreement between microbial enumeration and other evaluation
      techniques for natural bioremediation (e.g., geochemical indicator analysis,
      tracer study). Results suggest that the microbial enumeration is useful in
      assessing the occurrence, efficiency, and status of the bioremediation. Because
      this technique provides insight into factors controlling contaminant
      biodegradation, it could be performed as the supplemental method for natural
      bioremediation evaluation at petroleum-hydrocarbon spill sites.

PMID- 11337842
TI  - A modelling approach to global nitrate leaching caused by anthropogenic
      fertilisation.
AB  - Water quality associated with nitrate (NO3-) leaching from agricultural soils is
      an important environmental issue. This paper describes a new modelling approach
      to quantitatively evaluate the effect of the use of fertilisers on global nitrate
      leaching. A global process-based simulation model was previously developed for
      the nitrogen cycle in terrestrial ecosystems, in which soil inorganic nitrogen in
      the form of ammonium (NH4+) and NO3- was considered. After introducing data on
      world fertiliser consumption (FAO, 1995) into the steady-state model, the extent
      of disturbance to the nitrogen cycle caused by fertilisation was calculated.
      Although fertilisation resulted in an annual increase in net primary production
      (NPP, represented as carbon) of 18 Gt year-1, NO3- leaching and gaseous losses of
      nitrogen oxides and ammonia were also accelerated. Most regions with heavy
      fertiliser application (over 100 kg ha-1 year-1) showed a high annual leaching
      load equal to or more than 20 kg ha-1 year-1. About 2.5% of the land area
      occupied by terrestrial ecosystems suffered a serious leaching load of more than
      30 kg ha-1 year-1. Of the total amount of applied fertilisers (138 Tg year-1) 19%
      was lost to NO3- leaching, 8% to gaseous ammonia, and 3% to gaseous nitrogen
      oxides. The rest was assumed to be fixed in the ecosystems through vegetation
      uptake.

PMID- 11337843
TI  - Kinetic model of autotrophic denitrification in sulphur packed-bed reactors.
AB  - Autotrophic denitrification of synthetic wastewater by Thiobacillus denitrificans
      in upflow sulphur packed-bed reactors was studied in order to establish the
      process kinetics for prediction of effluent concentration. Elemental sulphur
      particles of different size served as energy substrate as well as the physical
      support for the microbial biofilm. Experiments were performed under operating
      conditions of (i) different flow rates at constant influent nitrate
      concentration; and (ii) different influent nitrate concentrations at constant
      flow rate. The experimental results show that autotrophic denitrification rates
      in upflow sulphur packed-bed reactors can be described by a half-order kinetic
      model for biofilms. It was found that the half-order kinetic constants of upflow
      packed-bed reactors are 2.94-3.60, 1.47-2.04, and 1.12-1.29 mg1/2/L1/2 h for
      sulphur particle sizes of 2.8-5.6, 5.6-11.2, and 11.2-16 mm, respectively. The
      half-order kinetic constants could be related to the specific surface area of the
      reactor media by a simple equation. Successful application of the half-order
      reaction rate model was demonstrated for an actual wastewater (nitrified
      leachate). A comparison with the literature showed that the half-order reaction
      rate constants for autotrophic denitrification using elemental sulphur are
      approximately one order of magnitude lower than those of heterotrophic
      denitrification. An improved stoichiometric equation for autotrophic
      denitrification using elemental sulphur as electronic donor is also proposed.

PMID- 11337844
TI  - Dredging-related mobilisation of trace metals: a case study in The Netherlands.
AB  - Mobilisation of contaminants is an important issue in environmental risk
      assessment of dredging projects. This study has aimed at identifying the effects
      of dredging on mobilisation of trace metals (Zn, Cu, Cd and Pb). The intensities
      and time scales of trace metal mobilisation were investigated during an
      experimental dredging project conducted under field conditions. The loss of
      contaminated dredge spoil is mainly reflected by increasing levels of trace
      metals in the suspended matter, dissolved trace metal concentrations in the water
      column are not significantly influenced by the dredging activities. This
      indicates a strong binding mechanism of trace metals to the solid phase or a fast
      redistribution over sorptive phases in response to oxidation of e.g. trace metal
      sulphides. Given the differences in levels of reactive phases (Mn, Fe, sulphides
      and organic matter) between the riverine suspended matter and the sediments,
      changes in the levels of these parameters in the suspended matter upon dredging
      may give information on the processes influencing the behaviour of trace metals
      and on the potential loss of sediment during dredging operations. Therefore, we
      recommend to routinely measure these parameters in studies on contaminant
      behaviour related to dredging activities.

PMID- 11337845
TI  - Abiotic hydrolysis of the detergent builder tripolyphosphate by hydrous manganese
      dioxide.
AB  - The hydrolysis of tripolyphosphate to orthophosphate is facilitated by
      suspensions of amorphous manganese dioxide. Pyrophosphate is observed as an
      intermediate. The rate enhancement decreases with increasing pH. The weak
      sorption of orthophosphate on the oxide also decreases with increasing pH,
      indicating that the orthophosphate product would be bioavailable. The presence of
      calcium ions in natural waters increases both the rate of hydrolysis of
      tripolyphosphate and the extent of sorption of orthophosphate. Under some
      circumstances this abiotic mechanism could play a significant role in the
      hydrolysis of tripolyphosphate in the aquatic environment.

PMID- 11337846
TI  - Degradation of 2,4-dichlorophenol by immobilized iron catalysts.
AB  - The degradation of 2,4-Dichlorophenol (from now on 2,4-DCP) has been carried out
      on Nafion-Fe (1.78%) in the presence of H2O2 under visible light irradiation. A
      solution containing 2,4-DCP (TOC 72 mg C/L)) is seen to be mineralized in
      approximately 1 h in the presence of H2O2 (10 mM) under solar simulated visible
      light (80 mW cm-2) at pH values between 2.8 and 11. Homogeneous photo-assisted
      Fenton reactions were capable of mediating 2,4-DCP degradation only up to pH 5.4.
      The degradation kinetics of 2,4-DCP on Nafion-Fe membranes was more favorable
      than the one observed during Fenton photo-assisted processes at pH 2.8. The
      degradation of 2,4-DCP was investigated as a function of the substrate, oxidant
      concentration and applied light intensity. The Nafion-Fe was seen to be effective
      over many cycles during the photo-catalytic degradation of 2,4-DCP showing an
      efficient and stable performance during 2,4-DCP degradation without leaching out
      Fe(3+)-ions into the solution. Evidence is presented that the degradation at the
      surface of the Nafion-Fe membrane seems to be controlled by mass transfer and not
      by chemical reaction of the species in solution. The approach used to degrade 2,4
      DCP is shown to be valid for other chloro-carbons like 4-chlorophenol, 2,3
      chlorophenol and 2,4,5-trichlorophenol.

PMID- 11337847
TI  - Ultrasonic waste activated sludge disintegration for improving anaerobic
      stabilization.
AB  - The pretreatment of waste activated sludge by ultrasonic disintegration was
      studied in order to improve the anaerobic sludge stabilization. The ultrasound
      frequency was varied within a range from 41 to 3217 kHz. The impact of different
      ultrasound intensities and treatment times was examined. Sludge disintegration
      was most significant at low frequencies. Low-frequency ultrasound creates large
      cavitation bubbles which upon collapse initiate powerful jet streams exerting
      strong shear forces in the liquid. The decreasing sludge disintegration
      efficiency observed at higher frequencies was attributed to smaller cavitation
      bubbles which do not allow the initiation of such strong shear forces. Short
      sonication times resulted in sludge floc deagglomeration without the destruction
      of bacteria cells. Longer sonication brought about the break-up of cell walls,
      the sludge solids were distintegrated and dissolved organic compounds were
      released. The anaerobic digestion of waste activated sludge following ultrasonic
      pretreatment causing microbial cell lysis was significantly improved. There was
      an increase in the volatile solids degradation as well as an increase in the
      biogas production. The increase in digestion efficiency was proportional to the
      degree of sludge disintegration. To a lesser degree the deagglomeration of sludge
      flocs also augmented the anaerobic volatile solids degradation.

PMID- 11337848
TI  - Biodegradability of ethylenediamine-based complexing agents.
AB  - Biological degradability of ethylenediamine derivatives depends on the type and
      number of substituents. The susceptibility to biodegradation decreases in the
      sequence of substituents -COCH3, -CH3, -C2H5, -CH2CH2OH, -CH2COOH and with
      polysubstitution. The biodegradability depends also on the kind and number of
      nitrogen atoms. Complexing agents with a single-nitrogen atom in the molecule
      (e.g. NTA) succumb relatively readily to biodegradation whereas, compounds with
      two or more tertiary amino groups are biologically highly stable and do not
      undergo biodegradation even in experiments with activated sludge adapted at an
      age of up to 30 days (EDTA, DTPA, PDTA, HEDTA). A lowering of the degree of
      substitution brings about an increased susceptibility to biodegradation. This
      holds, e.g., for replacement of tertiary amino groups with secondary ones; thus
      the symmetrically disubstituted ethylenediamine-N,N'-diacetic acid (EDDA)
      possesses still sufficient complexing ability while belonging already to the
      group of potentially degradable substances.

PMID- 11337849
TI  - Treatment of olefin plant spent caustic by combination of neutralization and
      Fenton reaction.
AB  - Spent caustic from olefin plants contains much H2S and some mercaptans, phenols
      and oil. A new treatment process of spent caustic by neutralization followed by
      oxidation with Fenton's reagent (Fe2+/H2O2) was successfully developed. Over 90%
      of dissolved H2S were converted to gas phase by neutralization at pH = 5 and T =
      70 degrees, and the vent gas stream could be introduced to sulfur recovery plant.
      The neutralized liquid was oxidized with OH. free radical, which was provided by
      a Fenton's reagent. The residual sulfides in the neutralized spent caustic were
      oxidized to less than 0.1 mg/L. The total COD removal of spent caustic is over
      99.5% and the final COD value of the effluent can be lower than 100 mg/L under
      the following oxidation conditions: reaction time = 50 min, T = 90 degrees, Fe2+
      = 100 mg/L, and a stoichiometric H2O2/COD = 1.1. The value is better than the 800
      mg/L value obtained by common WAO process. The optimum pH of the Fenton reaction
      is around 2 for this process, and the oxidation step can maintain a pH value in
      the range of 1.8-2.4. Moreover, the iron catalyst can be recycled without
      affecting process effectiveness thus preventing secondary pollution.

PMID- 11337850
TI  - Use of artificial neural network in the prediction of algal blooms.
AB  - A model to quantify the interactions between abiotic factors and algal genera in
      Lake Kasumigaura, Japan was developed using artificial neural network technology.
      Results showed that the timing and magnitude of algal blooms of Microcystis,
      Phormidium and Synedra in Lake Kasumigaura could be successfully predicted. As
      for the newly occurring dominant Oscillatoria, results were not satisfactory. The
      evaluation of the importance of factors showed that Microcystis, Phormidium,
      Oscillatoria and Synedra were alkalophilic. The algal proliferation for
      Microcystis, Oscillatoria and Synedra decrease due to the increase in total
      nitrogen, while the growth of Phormidium is enhanced with more nitrogen. In
      addition, the algal density is affected by zooplankton grazing but with the
      exception of Phormidium due to it being poor food source. Algal responses to the
      orthogonal combinations of the external environmental factors, chemical oxygen
      demand, pH, total nitrogen and total phosphorus at three levels were modeled.
      Various combinations of environmental factors enhance the proliferation of some
      algae while other combinations inhibit bloom formation.

PMID- 11337851
TI  - Clogging of a limestone fracture by stimulating groundwater microbes.
AB  - Biological clogging is promoted in aquifers either to contain or to remediate
      groundwater. In this study, an apparatus able to detect small changes in
      hydraulic conductivity (K) was developed to measure the clogging of a single
      fracture in limestone, following microbial stimulation. The fracture had a 2.5
      mm2 section and was 50 cm long. Prior to the inoculation of the limestone, the
      sequencing of representative clones from 16S rRNA genes isolated from
      groundwater, showed significant affiliation with Cytophaga spp., Arcobacter spp.
      and Rhizobium spp. These bacteria are known to secrete extracellular polymeric
      substances and form biofilms. When nutrients were added to the inoculated
      limestone, a decrease in K occurred after 8 days, reaching 0.8% of its initial
      value after 22 days (Kfi = 340 cm min-1). This study showed that a stimulation of
      indigenous microbes from groundwater effectively clogged a macrofracture in
      limestone, suggesting the potential application of biobarriers in fractured rock
      aquifers.

PMID- 11337852
TI  - A model for membrane bioreactor process based on the concept of formation and
      degradation of soluble microbial products.
AB  - A mathematical model of soluble microbial products (SMPs) formation-degradation
      was established based on the activated sludge model no. 1 and was applied to the
      membrane bioreactor process with high concentration of activated sludge under
      intermittent aerobic operational condition. The simulation results were in good
      agreement with the experimental data which indicated that the coefficients used
      in the model could successfully describe the treatment performance. The most
      advantage of this modified model over the conventional one was that the
      significant importance of SMP existence was demonstrated and the model provided
      an reasonable comprehension for SMP concept. The present study demonstrated that
      SMPs contributed most to the organic matter in the effluent, and the results
      coincided well with the observations of many other researchers.

PMID- 11337853
TI  - Adsorption of arsenite and arsenate within activated alumina grains: equilibrium
      and kinetics.
AB  - Equilibrium and kinetic adsorption of tri-valent (arsenite) and penta-valent
      (arsenate) arsenic to activated alumina is elucidated. The properties of
      activated alumina, including porosity, specific surface area, and skeleton
      density were first measured. A batch reactor with temperature control was
      employed to determine both adsorption capacity and adsorption kinetics for
      arsenite and arsenate to activated-alumina grains. The Freundlich and Langmuir
      isotherm equations were then used to describe the partitioning behavior for the
      system at different pH. A pore diffusion model, coupled with the observed
      Freundlich or Langmuir isotherm equations, was used to interpret an observed
      experimental adsorption kinetic curve for arsenite at one specific condition. The
      model was found to fit with the experimental data fairly well, and pore diffusion
      coefficients can be extracted. The model, incorporated with the interpreted pore
      diffusion coefficient, was then employed to predict the experimental data for
      arsenite and arsenate at various conditions, including different initial arsenic
      concentrations, grain sizes of activated alumina, and system pHs. The model
      predictions were found to describe the experimental data fairly well, even though
      the tested conditions substantially differed from one another. The agreement
      among the models and experimental data indicated that the adsorption and
      diffusion of arsenate and arsenite can be simulated by the proposed model.

PMID- 11337854
TI  - Oxygen transfer rate estimation in oxidation ditches from clean water
      measurements.
AB  - Standard methods for the determination of oxygen transfer rate are based on
      assumptions that are not valid for oxidation ditches. This paper presents a
      realistic and simple new method to be used in the estimation of oxygen transfer
      rate in oxidation ditches from clean water measurements. The new method uses a
      loop-of-CSTRs model, which can be easily incorporated within control algorithms,
      for modelling oxidation ditches. Further, this method assumes zero oxygen
      transfer rates (KLa) in the unaerated CSTRs. Application of a formal estimation
      procedure to real data revealed that the aeration constant (k = KLaVA, where VA
      is the volume of the aerated CSTR) can be determined significantly more
      accurately than KLa and VA. Therefore, the new method estimates k instead of KLa.
      From application to real data, this method proved to be more accurate than the
      commonly used Dutch standard method (STORA, 1980).

PMID- 11337855
TI  - The effect of decreased ambient temperature on the biological nitrification and
      denitrification of a high ammonia landfill leachate.
AB  - This research investigated the nitrogen removal capabilities of a pre- and post
      denitrification process, when treating sanitary landfill leachate containing an
      ammonia concentration of over 2200 mg N/L, at operating temperatures down to 10
      degrees C. The treatment system employed is generally known as a 4-Stage
      Bardenpho process. Two parallel systems were operated throughout the study; each
      system had an aerobic solids retention time of 20 days and an external recycle
      ratio (return activated sludge) of about 3:1. During the entire experimental
      period, one system used an internal recycle ratio of about 4:1, while the other
      system used one of 3:1. Methanol was used as supplementary carbon source for
      denitrification. When operating temperature was decreased from 20 to 17 degrees
      C, an approximate 15% decrease in denitrification was immediately experienced
      within both systems, with no noticeable affect on nitrification. This was an
      unexpected result. Subsequently, the temperature was further decreased to 14
      degrees C, and finally to 10 degrees C. With the temperature at 14 degrees C,
      aerobic wasting was also stopped and methanol loading was progressively decreased
      to match actual denitrification requirements. At 10 degrees C, both systems
      suffered major nitrification and denitrification inhibition. Changes in operating
      parameters, such as a decrease in influent ammonia and methanol loading, as well
      as an increase in ambient temperatures, from 10 to 15 degrees C, did not
      significantly improve overall system performance, within a reasonable time frame.
      Both denitrification and nitrification problems were mainly attributed to
      decreased ambient temperature, although other possible factors were noted; at
      project completion, about 50% of the incoming ammonia was being removed across
      the system.

PMID- 11337856
TI  - Degradation of phenolic waste waters over Ni-oxide.
AB  - The low-temperature oxidation of phenol in an aqueous phase in the presence of Ni
      oxide system has been studied. The effects of pH, temperature and the catalyst
      amount on the efficiency of the oxidation process have been investigated. The
      results obtained show that phenol is completely oxidized to harmless products-
      carboxylic acids and CO2 at ambient temperature and pH 6.0-7.0. The simple scheme
      for this synthesis of the Ni-oxide system and its regeneration is a prerequisite
      for its application to the purification of waste waters containing toxic
      compounds.

PMID- 11337857
TI  - On the degradability of printing and dyeing wastewater by wet air oxidation.
AB  - A modified first-order kinetics model was used to study the wet air oxidation of
      printing and dyeing wastewater. The model simulations are in good agreement with
      experimental data. The results indicate that a certain fraction of organic
      pollutants in the printing and dyeing wastewater could not be removed even at
      elevated temperature and prolonged reaction time. The ratio of degradable organic
      matter is found independent of temperature and can be improved by using a
      catalyst.

PMID- 11337858
TI  - Use of conductivity to monitor the treatment of acid mine drainage by sulphate
      reducing bacteria.
AB  - Measurements of electrical conductivity were obtained during treatment of acid
      mine drainage (AMD) by sulphate-reducing bacteria (SRB) in fed-batch column
      reactors. The advantages of this method are that it is non-invasive, non
      destructive, and rapid, giving real-time information. Conductivity measurements
      were taken on an hourly basis throughout the course of several experiments in
      which the SRB were exposed to different quantities of fresh AMD. Simultaneous
      measurements were taken in a column in which no SRB were present but were also
      exposed to the same volumes of fresh AMD. As treatment of the AMD progressed,
      increases in conductivity were measured, generally localized to two regions in
      the gravel bed: the top and bottom 10 cm (4"). Changes in conductivity were not
      always coincident with changes in ORP and pH, indicating that conductivity may be
      a more sensitive tool for locating and monitoring specific zones of SRB activity.

PMID- 11337859
TI  - Application of ferrous hydrogen peroxide for treatment of DSD-acid manufacturing
      process wastewater.
AB  - A pretreatment method for the biological treatment of wastewater from 4,4'
      diaminostilbene-2,2'-disulfonic acid (DSD-acid) manufacturing processes, a
      refractory dye intermediate wastewater, based on combined ferrous hydrogen
      peroxide oxidation and coagulation-flocculation, was developed. When the
      wastewater was treated with ferrous hydrogen peroxide oxidation ([Fe2+] = 2.7
      mmol/L, [H2O2] = 0.21 mol/L) after a flocculation using an organic flocculant TS
      1 at a dosage of 3 g/L, the overall COD and color removals were 64 and 62%,
      respectively. BOD5/COD value of the effluent was 0.3. Ferrous hydrogen peroxide
      oxidation treatment can reduce the solubility of organic molecules with sulfonic
      group and increase the efficiency of coagulation treatment. The COD and color
      removals were both more than 90% when FeCl3 was used as the coagulation (dosages
      of two-step coagulation were 0.031 and 0.012 mol/L respectively) after a ferrous
      hydrogen peroxide oxidation pretreatment at a H2O2 dosage of 0.06 mol/L.

PMID- 11337860
TI  - Amount concentrations in aquatic chemistry.
AB  - Usually, two main terms for concentration are used: amount concentration and mass
      concentration. Mass concentrations can significantly distort the actual
      presentation of inorganic and organic compounds in the mixture. They cannot be
      used when comparing quantity and properties of different compounds, when
      explaining reaction kinetics, reaction mechanisms and when investigating
      relationships between concentration and chemical or biological activity. In these
      cases it is necessary to prefer amount concentrations. "Equivalent concentration"
      is based on the charge balance of ions in the solution and not on their actual
      number. The dimension of the equivalent concentration is the same as that of
      amount concentration (e.g., mmol l-1) which concerns also ANC or BNC (alkalinity
      or acidity).

PMID- 11337861
TI  - By-products formation during drinking water disinfection: a tool to assess
      disinfection efficiency?
AB  - In drinking water treatment, the inactivation of microorganisms increases with
      increasing disinfectant exposure (product of concentration and contact time, CT).
      Also, the formation of undesired (toxic) disinfection by-products increases with
      CT. The present study proposes a new concept that uses this undesired side effect
      of chemical water disinfection for a fast and reliable test of treatment
      efficiency. In laboratory systems, bromate formation during ozonation and the
      formation of trihalomethanes during chlorination were used to calculate the
      disinfectant exposure, which is a measure for the achieved degree of
      disinfection.

PMID- 11337862
TI  - Atrazine uptake, elimination, and bioconcentration by periphyton communities and
      Daphnia magna: effects of dissolved organic carbon.
AB  - The bioconcentration and toxicokinetics of atrazine in three different periphyton
      communities and in laboratory reared Daphnia magna were studied in natural and
      artificial waters with different dissolved organic carbon (DOC) concentrations
      and qualities. The exposure concentrations were similar to those short-lived peak
      concentrations found in contaminated waters. Atrazine uptake and elimination were
      very fast, and the bioconcentration was low both in periphyton and D. magna. The
      bioconcentration factors in D. magna were approx. 16% of those in periphyton. The
      uptake and elimination rates were also higher in periphyton than in Daphnia. The
      periphyton properties affected the bioconcentration of atrazine more than the DOC
      concentration and water quality. A steady state was reached within a few hours of
      uptake by the periphyton and within 24 h by D. magna. A residue of atrazine was
      left in the periphyton and D. magna after an 8-h biphasic depuration with clearly
      distinct fast and slow phases. In D. magna, atrazine may be eliminated during the
      normal life span of the organism. These results suggest that DOC has a minor
      influence on the toxicokinetics of atrazine.

PMID- 11337863
TI  - Metabolism of the polycyclic aromatic hydrocarbon fluoranthene by the polychaete
      Capitella capitata species I.
AB  - Previous studies have shown that infaunal deposit feeders may enhance the loss of
      organic contaminants from sediments. However, the extent to which this occurs as
      a result of sediment microbial stimulation, porewater flushing, or
      biotransformation by infauna remains unclear. The purpose of this study was to
      determine whether the infaunal polychaete Capitella sp. I is able to metabolize
      the polycyclic aromatic hydrocarbon (PAH) fluoranthene and to provide an initial
      characterization of the metabolites produced. Our results showed that Capitella
      sp. I is able to metabolize fluoranthene to more hydrophilic products and that,
      after 24 h in clean sediment, fluoranthene could no longer be detected in worm
      tissues whereas a number of fluoranthene-derived metabolites were present. None
      of the metabolites released or retained by worms resembled known bacterial
      metabolites, suggesting that Capitella, and not bacteria associated with its gut
      or body surface, were responsible for the biotransformation of fluoranthene in
      our system. On the basis of ultraviolet maxima, peak shape, relative height, and
      order of elution, tentative identities of two metabolites (i.e., 3- and 8
      hydroxyfluoranthene) are proposed. The results demonstrate that, in addition to
      their effects on sediment geochemical properties, infaunal polychaetes such as
      Capitella can enhance the degradation of sediment-associated contaminants by
      directly metabolizing them.

PMID- 11337864
TI  - An evaluation of the etiology of reduced CYP1A1 messenger RNA expression in the
      Atlantic tomcod from the Hudson River, New York, USA, using reverse transcriptase
      polymerase chain reaction analysis.
AB  - Adult Atlantic tomcod, Microgadus tomcod, from the Hudson River, New York State,
      USA, exhibit reduced inducibility of hepatic cytochrome P4501A1 (CYP1A1) mRNA
      compared with adult tomcod from the cleaner Miramichi River, New Brunswick,
      Canada, when treated with coplanar polychlorinated biphenyl (PCB) congeners or
      2,3,7,8-tetrachlorodibenzo-p-dioxin. In contrast, little difference in CYP1A1
      inducibility is observed between tomcod from these two rivers when treated with
      polycyclic aromatic hydrocarbons (PAHs). We sought to determine if impaired
      hepatic CYP1A1 inducibility in Hudson River tomcod results from a
      multigenerational, genetic adaptation or a single generational, physiological
      acclimation. Embryos and larvae from controlled experimental crosses of Hudson
      River and Miramichi River parents were exposed for 24 h to water-borne PCB
      congener 77 (10 ppm), benzo[a]pyrene (BaP; 10 ppm), or dimethysulfoxide, and
      CYP1A1 expression was assessed in individual larva using competitive reverse
      transcriptase polymerase chain reaction (RT-PCR) analysis. The CYP1A1 mRNA was
      significantly induced in larvae from both populations by BaP (47- and 52-fold)
      and PCB 77 (9- and 22-fold), although levels of expression were higher in
      offspring of Miramichi matings. Most important, CYP1A1 mRNA was significantly
      induced by PCB 77 in larvae from Hudson River parents. Concentrations of dioxin,
      furan, and PCB congeners were measured in livers and eggs of female tomcod from
      these two locales to quantify the extent of maternal transfer of contaminants.
      For both rivers, wet-weight contaminant concentrations were significantly higher
      (4-7 times) in livers than in eggs of the same females, suggesting that a
      threshold level of contaminants may have to be reached before CYP1A1
      transcription is impaired. We conclude that reduced inducibility of hepatic
      CYP1A1 mRNA in adult tomcod from the Hudson River is most consistent with single
      generational acclimation.

PMID- 11337865
TI  - Uptake and diverse effects of polycyclic aromatic hydrocarbons on the metabolic
      activity of Elliptio complanata measured by calorespirometry.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are important contaminants of world water
      resources, with effects on aquatic life. Metabolic responses to short-term acute
      toxicities of naphthalene, anthracene, and chrysene were investigated in the
      freshwater bivalve mollusk Elliptio complanata using differential scanning
      calorespirometry coupled with uptake and scanning electron microscopy. Comparing
      the uptakes of naphthalene, anthracene, and chrysene with that of inulin, which
      is known to occupy only extracellular space, showed that all compounds studied
      were taken up. The PAHs studied had diverse effects on the metabolic activity of
      E. complanata. Naphthalene and, to a lesser degree, chrysene caused stimulation
      of heat rates, possibly due to uncoupling of oxidative metabolism. Differential
      scanning calorespirometry coupled with studies of rates of oxygen consumption by
      the gill tissue exposed to the PAHs showed similar diverse patterns of
      respiratory rate stimulation and inhibition. Analysis of results of scanning
      electron microscopy suggested that irreversible damage to the gill tissue
      occurred in the presence of anthracene but not in the presence on naphthalene or
      chrysene. The batch calorespirometric method coupled with uptake and spectroscopy
      proved to be a useful technique to assess the toxicity of PAHs on the control of
      energy flux in gills of a freshwater bivalve mollusk.

PMID- 11337866
TI  - Effects of sulfate on the acute toxicity of selenate to freshwater organisms.
AB  - This study evaluated the relationship between ambient sulfate concentrations and
      acute selenate toxicity to freshwater aquatic life. Previous studies indicated
      that increasing sulfate concentrations reduced selenate bioconcentration and
      toxicity. However, these studies generally were not conducted in a manner that
      was conducive to their use in deriving a water quality criterion. We compiled
      results from previous studies and generated additional data to help define a
      selenate-sulfate relationship for acute toxicity. Selenate toxicity was
      determined in standardized test waters with varying sulfate concentrations using
      Ceriodaphnia dubia, Gammarus pseudolimnaeus, Hyalella azteca, and Pimephales
      promelas as the test organisms. Analysis of test results indicated that a
      significant relationship does exist between acute selenate toxicity and ambient
      sulfate concentrations. Data from these tests and previous studies were combined
      to develop a statistical relationship sufficiently robust to derive a sulfate
      dependent water quality criterion for selenate. The relationship is similar to
      those commonly derived between divalent metals and hardness to adjust water
      quality criteria.

PMID- 11337867
TI  - Whole blood concentrations of organochlorines as a dose metric for studies of the
      glaucous gull (Larus hyperboreus).
AB  - In order to examine if whole blood concentrations of organochlorines (OCs) is an
      appropriate dosimetric parameter for use in ecotoxicological studies of free
      living birds, a number of incubating glaucous gulls (Larus hyperboreus) were
      repeatedly sampled within and between subsequent breeding seasons. The wet weight
      concentrations of selected OCs, differing in persistence and fat solubility, were
      compared and it was assessed to what extent present concentrations could be
      predicted from concentrations previously measured in the individuals. There were
      only a few significant differences in the blood concentrations of the selected
      OCs within and between seasons. The most persistent compound, polychlorinated
      biphenyl (PCB)-153, showed a low interindividual variability, and between
      seasons, 70% of the variance could be explained by the level in the previous
      year, while changes in body condition and blood lipid percentage were of less
      importance. For PCB-101, the predictability of the present blood concentration
      from the previous concentration was lower than for PCB-153, and changes in body
      condition and blood lipid percentage explained a higher proportion of the
      variance. The present level of alpha-hexachlorocyclohexane (HCH) could not be
      predicted from the previous level. Sex did not explain any significant proportion
      of the variance in OC concentrations when previous level and changes in body mass
      and blood lipid were included in the statistical models. Thus, for the most
      persistent OCs, concentration in the blood of incubating glaucous gulls is
      representative for the interindividual differences over time and whole blood
      concentrations of OCs appear adequate as a dose metric in ecotoxicological
      studies.

PMID- 11337868
TI  - Relative potencies of polychlorinated dibenzo-p-dioxin, dibenzofuran, and
      biphenyl congeners to induce cytochrome P4501A mRNA in a zebrafish liver cell
      line.
AB  - Induction of cytochrome P4501A (CYP1A) mRNA by polychlorinated dibenzo-p-dioxin
      (PCDD), polychlorinated dibenzofuran (PCDF), and polychlorinated biphenyl (PCB)
      congeners was measured in a zebrafish liver (ZF-L) cell line. The ZF-L cells were
      far less sensitive to PCDD, PCDF, and PCB congeners than were other fish cell
      lines. The 2,3,7,8-PCDDs, 2,3,7,8-PCDFs, and PCB 126 caused dose-related
      induction. All other PCBs tested, including other coplanar as well as ortho
      substituted congeners, were ineffective at inducing CYP1A. The potency of each
      congener that gave a response, relative to 2,3,7,8-tetrachlorodibenzo-p-dioxin,
      was determined. The ZF-L cell-derived relative potency values (REPs) are similar
      to other in vitro REPs in that the ZF-L cell-derived REPs are generally higher
      than those derived from in vivo models. Furthermore, the ZF-L cell-derived REPs
      are generally within fivefold of REPs determined in a variety of rainbow trout
      systems when the same endpoint in the same tissue are compared. Analysis of these
      data indicates that REPs based on molecular and biochemical responses in
      sensitive and insensitive species are similar, but overestimate relative in vivo
      toxicity in the rainbow trout. The ZF-L cell-derived REPs expand the database of
      REPs, providing additional information that will be useful in quantifying the
      uncertainty associated with applying consensus fish-specific toxic equivalency
      factors in ecological risk assessment.

PMID- 11337869
TI  - Atrazine remediation in wetland microcosms.
AB  - Laboratory wetland microcosms were used to study treatment of atrazine in
      irrigation runoff by a field-scale-constructed wetland under controlled
      conditions. Three experiments, in which 1 ppm atrazine was added to the water
      column of three wetland, one soil control, and one water control microcosm, were
      conducted. Atrazine dissipation from the water column and degradate formation
      (deethylatrazine [DEA]; deisopropylatrazine [DIA]; and hydroxyatrazine [HA]) were
      monitored. Atrazine dissipation from the water column of wetland microcosms was
      biphasic. Less than 12% of the atrazine applied to wetland microcosms remained in
      the water column on day 56. Atrazine degradates were observed in water and
      sediment, with HA the predominant degradate. Analysis of day 56 sediment samples
      indicated that a significant portion of the initial application was detected as
      the parent compound and HA. Most probable number (MPN) assays demonstrated that
      atrazine degrader populations were small in wetland sediment. Wetland microcosms
      were able to reduce atrazine concentration in the water column via sorption and
      degradation. Based on results from this study, it is hypothesized that plant
      uptake contributed to atrazine dissipation from the water column.

PMID- 11337870
TI  - Influences of metal concentration in phytoplankton and seawater on metal
      assimilation and elimination in marine copepods.
AB  - Radiotracer experiments were conducted to examine the influence of the
      concentration of Cd, Se, and Zn in ingested phytoplankton (dinoflagellate
      Prorocentrum minimum and diatom Thalassiosira weissflogii) and in ambient
      seawater on metal assimilation and elimination efficiencies of three marine
      copepods, Acartia spinicauda, Paracalanus aculeatus, and Calanus sinicus. The
      assimilation efficiencies (AEs) decreased by 1.7 to 2.0 times, 1.4 to 4.1 times,
      and 1.3 to 2.2 times in the copepods with an increase in metal concentration in
      ingested algae by 16 to 84 times, 14 times, and 45 to 153 times, for Cd, Se, and
      Zn, respectively. However, the physiologic turnover rate constant was relatively
      independent of the metal concentration in copepods. No evidence was found of any
      interaction between Cd and Zn in their assimilation by copepods. Assimilation
      efficiencies of Cd were higher in copepods feeding on the dinoflagellate P.
      minimum, whereas the AEs of Zn were higher in copepods feeding on the diatom T.
      weissflogii. Differences in metal distribution in algal cytoplasm at different
      ambient metal concentrations may be partially responsible for the observed
      influence of metal concentration in algal cells on metal assimilation in
      copepods. However, metal desorption within the gut of the copepod may have little
      influence on metal assimilation, as a result of the short gut residence time of
      food particles and the neutral gut pH. Our study also indicated that the
      ingestion rate of copepods was reduced by a higher concentration of Cd and Se,
      but was not affected by Zn concentration in the food particles. Consequently,
      partial regulation of metal trophic transfer in response to increasing metal
      contamination may be achieved by a change in metal assimilation efficiency and
      the ingestion activity of the copepod, but not by changes in metal turnover rates
      from the animals.

PMID- 11337871
TI  - Effects of salinity and chemical speciation on cadmium accumulation and toxicity
      to two mysid species.
AB  - The estuarine environment is characterized by frequent fluctuations in salinity.
      Consequently, organisms used for environmental monitoring of estuaries must be
      euryhaline so that their laboratory responses to chemical pollutants are measured
      under the full range of salinity exposures experienced in the field. Neomysis
      integer and Praunus flexuosus are two potential candidates for use in
      environmental monitoring of European estuaries. The present study assesses the
      effects of salinity on survival, trace metal accumulation, and toxicity to these
      two mysid species. Neomysis integer was more euryhaline, showing 100% survival at
      1 to 40@1000 compared with P. flexuosus, which showed 100% survival at salinities
      of 10 to 40@1000. Toxicity of the free cadmium ion to both species was unaffected
      by salinity, and 96-h LC50s ranged from 4.8 to 15 micrograms Cd2+/L for N.
      integer and from 12.3 to 16 micrograms Cd2+/L for P. flexuosus. The 7-d LC50s
      ranged from 1.0 to 4.2 and 4.8 to 5.3 micrograms Cd2+/L for N. integer and P.
      flexuosus, respectively. No effect of exposure salinity was found on cadmium body
      burdens of mysids exposed for 7 d to 0.5 and 1.0 microgram Cd2+/L. The results
      are discussed in terms of possible effects of osmoregulatory mechanisms on trace
      metal uptake, accumulation, and toxicity.

PMID- 11337872
TI  - Effects of di(2-ethylhexyl) phthalate and dibutyl phthalate on the collembolan
      Folsomia fimetaria.
AB  - Lethal and sublethal effects of di(2-ethylhexyl) phthalate (DEHP) and dibutyl
      phthalate (DBP) on adult individuals of the collembolan Folsomia fimetaria were
      investigated in the laboratory by the use of small microcosms. Effects of DEHP
      and DBP were also tested on newly hatched collembolans in a multidish system. The
      endpoints were juvenile mortality, growth, and development. When exposed to DEHP,
      adults and juveniles were unaffected at all test concentrations, that is, up to
      5,000 mg/kg. However, DBP caused increased adult mortality at 250 mg/kg and
      juvenile mortality at 25 mg/kg. For DBP, adult reproduction was a more sensitive
      endpoint than was survival, with an EC10 and EC50 of 14 and 68 mg/kg,
      respectively. Juvenile molting frequency seems to be a sensitive parameter,
      because number of cuticles produced by young springtails was reduced at 1 mg/kg.
      Toxicity was reduced when soil spiked with DBP was stored at 20 degrees C for a
      period of up to 28 d before adding the animals. Reduction in toxicity of DBP may
      be due a combination of degradation, evaporation, and adsorption of DBP to soil
      material. This was confirmed by chemical analyses, which showed a rapid initial
      disappearance followed by a much slower disappearance. Our results lead to the
      overall conclusion that significant adverse effects of phthalates on collembolans
      are not likely to occur as a result of normal sewage sludge application.

PMID- 11337875
TI  - Amendment of sediments with a carbonaceous resin reduces bioavailability of
      polycyclic aromatic hydrocarbons.
AB  - We evaluated the effectiveness of Ambersorb, a carbonaceous resin, in reducing
      bioavailability of polycyclic aromatic hydrocarbons (PAHs) in contaminated
      sediments collected from the field. In laboratory studies, sediment pore-water
      concentrations of eight unsubstituted PAHs were significantly decreased after
      resin addition. Reduced PAH concentrations in oligochaete tissues from a
      laboratory bioaccumulation test, along with increased survival/reproduction and
      reduced photo-enhanced toxicity and sediment avoidance, also resulted from
      sediment treatment with Ambersorb. Resin amendment also decreased pore-water PAH
      concentrations in field deployed sediments but did not improve benthic
      invertebrate colonization. Prediction of partitioning of PAHs between solid and
      aqueous phases in the test sediments was complicated by the presence of coal and
      soot. However, accurate predictions of bioavailability were achieved based on
      pore-water chemistry. Overall, these studies show that the addition of high
      affinity sorbents effectively reduces pore-water PAH concentrations and
      bioavailability and suggests that sorbent addition may serve as an option for in
      situ remediation of some contaminated sediments.

PMID- 11337874
TI  - Phototactic behavior of Daphnia and the continuous monitoring of water quality:
      interference of fish kairomones and food quality.
AB  - We carried out a laboratory study to evaluate the sensitivity of phototactic
      behavior of Daphnia magna to sublethal concentrations of pentachlorophenol (PCP)
      and copper. More specifically, we determined whether the sensitivity of a D.
      magna clone to those pollutants is influenced by food quality and the presence of
      fish kairomones. Test animals were fed either unicellular green algae
      (Scenedesmus acutus) or fresh baker's yeast (Saccharomyces cerevisiae) and were
      cultured in the presence or absence of fish kairomones. Four concentrations of
      PCP (0.4, 0.8, 1.2, and 1.6 mg/L PCP) and one concentration of copper (0.02 mg/L
      Cu2+) in International Standards Organisation (ISO, Geneva, Switzerland) standard
      medium were applied in the experiments. Animals were exposed for 3 h to the
      pollutants prior to the experiments. In the absence of fish kairomones, a strong
      negative relationship between the phototactic index and nominal sublethal
      concentrations of PCP was found in animals fed either algae or yeast. The
      sensitivity of the Daphnia clone to sublethal concentrations of PCP was, however,
      less clear cut in animals fed yeast than in animals fed algae. The detection
      limit was 0.4 mg/L PCP with algae as food but was as high as 1.2 mg/L PCP when
      yeast was used as food. The ability to detect sublethal concentrations of copper
      and PCP using phototactic behavior was lost when the clones were cultured in the
      presence of fish kairomones. At a concentration of 0.02 mg/L Cu2+ and in the
      absence of fish kairomones, the D. magna clone tested became significantly less
      positively phototactic than in the control treatment regardless of the quality of
      the food used to culture the test animals. These results suggest that assays
      using the phototactic behavior of Daphnia to monitor water quality should use
      genetically stable (clonal) material, positively phototactic, and insensitive to
      the presence of fish kairomones.

PMID- 11337873
TI  - Negative correlation between plasma thyroid hormone levels and chlorinated
      hydrocarbon levels accumulated in seals from the coast of Hokkaido, Japan.
AB  - Chlorinated hydrocarbon (CHC) levels in the blubber of larga seals (Phoca largha)
      and ribbon seals (Phoca fasciata) collected from the coastal waters of Hokkaido,
      Japan, were determined in order to assess the hormonal effects of CHC exposure in
      free-ranging pinnipeds. Plasma thyroid hormone levels, including total thyroxine
      (T4), free thyroxine (free T4), total triiodothyronine (T3), and free
      triiodothyronine (free T3), were also measured. Higher concentrations of
      polychlorinated biphenyl congeners (PCBs), dichlorodiphenyltrichloroethane and
      its metabolites, and chlordane compounds were found in the range of 380 to 2,600
      ng/g, 350 to 2,600 ng/g, and 120 to 760 ng/g on a wet-weight basis, respectively.
      Spearman rank correlation analyses showed that in larga seals, plasma total T3
      and free T3 levels negatively correlated with levels of all the CHCs analyzed,
      although there was no such correlation between total or free T4 levels and CHC
      concentrations. In ribbon seals, total T3 levels significantly decreased with an
      increase of di-ortho PCB (PCB170 and 180) residues. These findings indicated that
      the plasma T3 deficiency could be associated with some CHC exposure in larga and
      ribbon seals and that the responses of plasma thyroid hormones may be useful
      biomarkers for CHC exposure in ribbon seals.

PMID- 11337876
TI  - Localization of deposited polycyclic aromatic hydrocarbons in leaves of Plantago.
AB  - After deposition to foliage, polycyclic aromatic hydrocarbons (PAHs) may remain
      on the leaf surface, accumulate in the cuticular wax, or diffuse into the
      remaining interior of the plant. In a field study, the location of deposited PAHs
      in the leaves of two Plantago species was determined. To this aim, leaves of
      Plantago major and Plantago media were divided into three fractions. First, the
      leaves were washed (wash-off fraction), then cuticular wax was extracted (wax
      fraction). Finally, the remaining leaf material was extracted (interior
      fraction). The presence of PAHs could be demonstrated in all three fractions. For
      both plants, the distribution of PAHs over the three fractions changed with
      molecular weight (mol wt) of the PAHs. The wash-off fraction increased with
      increasing molecular weight, likely because high molecular-weight PAHs occur
      predominantly bound to particles, which can be readily washed off from the
      leaves. In contrast, the amount of PAHs detected in the interior of the leaves
      decreased with increasing molecular weight. This can be explained by a slow
      desorption of the PAHs from the particles and a low diffusion rate of the larger
      molecules. This study shows that washing reduces the amount of high molecular
      weight PAHs on plant surfaces. Therefore, washing of leafy vegetables is
      important to minimize human dietary intake of PAHs.

PMID- 11337877
TI  - Effect of bile salts, lipid, and humic acids on absorption of benzo[a]pyrene by
      isolated channel catfish (Ictalurus punctatus) intestine segments.
AB  - Dietary absorption of lipophilic contaminants may be a significant route of
      exposure in aquatic organisms. Bile salts, lipids, and humic acids are important
      factors that may influence the intestinal absorption of a contaminant such as
      benzo[a]pyrene (BaP). We hypothesized that bile salts, monoglycerides, and free
      fatty acids would increase BaP intestinal absorption, while triglycerides, humic
      acids, and sediment would decrease BaP intestinal absorption. We have established
      and validated an in vitro model to examine modification of 3H-BaP absorption in
      everted intestinal segments from channel catfish (Ictalurus punctatus). Uptake of
      BaP into the everted intestinal segments continued to increase over the times
      examined in this study (60 min) and apparently occurs passively; thus, fugacity
      based models of uptake are supported. Absorption of BaP into intestinal cells was
      significantly decreased by the addition of monoglycerides and free fatty acids to
      bile salts in the incubation media. Addition of triglycerides decreased BaP
      absorption even further. Humic acids may have decreased BaP intestinal
      absorption, while natural sediment may have increased BaP absorption. The results
      of this study suggest that all lipids may decrease intestinal uptake of
      lipophilic contaminants if they remain in unabsorbable excess in the intestinal
      lumen by retaining BaP in lipid/bile micelles. In contrast, if triglycerides are
      hydrolyzed into monoglycerides/free fatty acids prior to absorption, lipophilic
      contaminant uptake will likely be facilitated. Thus, it may be the hydrolytic
      state of lipids that determines its effects on BaP absorption. Humic acids alone
      may decrease dietary uptake of BaP, but our results suggest that other components
      in natural sediment may counteract this effect to cause a slight enhancement of
      BaP uptake. Further studies are needed to determine the dietary conditions
      necessary for bioaccumulation to contribute significantly to lipophilic
      contaminant body burdens in benthivorous fish. Finally, the everted intestinal
      segment technique has the potential to be used in other species and with
      different contaminants.

PMID- 11337878
TI  - Development of a freshwater aquatic toxicity database for ambient water quality
      criteria for methyl tertiary-butyl ether.
AB  - The detection of methyl tertiary-butyl ether (MTBE) in groundwater and surface
      water in recent years has drawn attention to its potential effects in aquatic
      ecosystems. To address concerns regarding MTBE environmental effects and to
      establish safe concentrations in surface waters, a collaborative effort was
      initiated in 1997 to develop aquatic toxicity databases sufficient to derive
      ambient water quality criteria for MTBE consistent with United States
      Environmental Protection Agency (U.S. EPA) requirements. Acute toxicity data for
      six species, chronic toxicity data for a fish and an invertebrate, and plant
      toxicity data were developed in order to complete the freshwater database. The
      toxicity tests followed U.S. EPA and American Society for Testing and Materials
      (ASTM, Philadelphia, PA, USA) procedures and were conducted in accordance with
      U.S. EPA Good Laboratory Practice guidelines. Based on measured exposure
      concentrations, acute toxicity endpoints ranged from 472 to 1742 mg MTBE/L, while
      chronic endpoints (IC25) were 57 to 308 mg MTBE/L. Aquatic invertebrates were
      generally more sensitive than fish to MTBE in both acute and chronic exposures.
      Acute-to-chronic ratios for fathead minnows and Daphnia magna were 3.4 and 11.3,
      respectively. The measured acute and chronic toxicity were within a 10-fold
      factor of toxicity predicted from quantitative structure-activity relationships
      for baseline toxicity or nonpolar narcosis typical of ether compounds. The data
      developed in this study were consistent with existing data and showed that MTBE
      has low acute and chronic toxicity to freshwater organisms. Reported
      environmental concentrations of MTBE are several orders of magnitude lower than
      concentrations observed to cause effects in freshwater organisms.

PMID- 11337879
TI  - The relation between extrapolated risk, expressed as potentially affected
      fraction, and community effects, expressed as pollution-induced community
      tolerance.
AB  - The results of toxicity tests can be used to calculate the potentially affected
      fraction (PAF) of species in an ecosystem at a given pollutant concentration
      using statistical extrapolation methods. The PAF curve indicates the fraction of
      species from the original community that may become inhibited at each elevated
      pollutant concentration and is a measure of the ecotoxicological risk. Pollution
      induced community tolerance (PICT) is a true community response that is measured
      under controlled conditions in the laboratory, using organisms from contaminated
      field sites. Microorganisms from experimental field plots with added Zn were
      exposed to various concentrations of Zn in the laboratory and the mineralization
      of 14C acetate was monitored. Microorganisms from plots with Zn concentrations
      above 124 mg/kg showed a significant increase in the effect concentration 10%
      (EC10) and, therefore, had a significant PICT. The pore-water concentrations of
      Zn in these field soils were in the same magnitude as the EC10 of the
      microorganisms from these soils. The PAF curve was calculated from previously
      reported toxicity tests with five different microbial species using the average
      and the standard deviation of the logarithmically transformed EC10 values. The
      average sensitivity of this PAF curve was similar to the EC50 of the acetate
      mineralization curve from the field plot without added Zn2+, but the PAF curve
      was less steep. Our experiments indicated that 27 to 84% of the original
      microbial species were inhibited at Zn concentrations from 334 to 1,858 mg/kg
      soil, respectively. Our results suggest that the PICT method can now also be used
      to quantify the fraction of the original species composition that is inhibited at
      a specific pollutant concentration.

PMID- 11337880
TI  - Determination and multivariate statistical analysis of biochemical responses to
      environmental contaminants in feral freshwater fish Leuciscus cephalus, L.
AB  - Modulations of 11 prospective biochemical markers of impacts of aquatic
      pollutants in liver tissue of chub (Leuciscus cephalus), caught at several
      sampling sites of a river with various pollution types and rates, were matched
      against analytical data of concentrations of organochlorine compounds, polycyclic
      aromatic hydrocarbons (PAHs), and heavy metals. Multivariate principal component
      analysis (PCA) of the field data showed general patterns of biochemical responses
      to different types of pollutants and relationships among the biomarkers.
      Cytochrome P4501A-dependent 7-ethoxyresorufin O-deethylase (EROD) activity,
      inducible by 2,3,7,8-tetrachlorodibenzo-p-dioxin and structurally related planar
      compounds, was strongly enhanced in the more contaminated areas. Compared with
      polychlorinated aromatic hydrocarbons, PAHs did not contribute so significantly
      to EROD induction. Testosterone 6 beta- and 16 alpha-hydroxylase activities, as
      an expression of the cytochrome P4503A27, were slightly increased at several
      sites but were significantly decreased in samples from some heavily polluted
      areas. Recently, these activities have been suggested as potential biomarkers of
      exposure to contaminants that do not induce cytochrome P4501A. In this study,
      their inhibition or induction was not associated with a specific class of
      monitored contaminants, and selectivities of these modulations are still to be
      investigated. Similar modulations of the prospective biochemical indicators of
      oxidative stress, including microsomal glutathione S-transferase activity,
      cytosolic glutathione S-transferase with ethacrynic acid, and glutathione
      reductase, were demonstrated by PCA. The pattern of the modulations of the
      microsomal nicotinamide adenine dinucleotide phosphate (NADPH)-dependent lipid
      peroxidation in vitro differed from the responses of the rest of oxidative stress
      parameters at some sampling sites. Further biochemical markers of oxidative
      stress under study, including in vivo lipid peroxidation, in vitro production of
      reactive oxygen species, and the concentration of metallothioneins did not
      correlate well with the concentrations of the contaminants. Principal component
      analysis demonstrated that the EROD activity, glutathione-dependent enzymes, and
      Fe(II)-enhanced lipid peroxidation formed a suitable battery of biomarkers of
      exposure.

PMID- 11337881
TI  - Biodegradation of poly(tetramethylene succinate-co-tetramethylene adipate) and
      poly(tetramethylene succinate) through water-soluble products.
AB  - Poly(tetramethylene succinate-co-tetramethylene adipate) (PBSA) and
      poly(tetramethylenesuccinate) (PBS) were hydrolyzed experimentally into water
      soluble oligomers and monomers by Chromobacterium extracellular lipase. The
      oligomers were identified by high-performance liquid chromatography-mass
      spectrometry and 1H-nuclear magnetic resonance, which indicated that a total of
      28 oligomer species were liberated from PBSA, and that 13 of them were identical
      to the hydrolysates from PBS. Moreover, 20 of the species were polyester-based
      compounds of monomer units, and the other 8 species were small amounts of
      diurethane compounds. Bis(hydroxybutyl) succinate (BSB) and bis(hydroxybutyl)
      hexamethylene dicarbamate (BHB) were the typical oligomers and were chemically
      synthesized. Biodegradability of BSB and BHB was examined for 28 d in the
      activated sludge, and analysis of the results of this study indicated that the
      final conversion rate of constituent carbon to carbon dioxide was estimated at 80
      mol% for BSB and 10 mol% for BHB. The remaining amount of carbon in the
      undegraded BHB was 20 mol%. In the presence of BSB, the biodegradability of BHB
      was increased by about 1.5 times. The suggestion was made that BSB induced a
      growth of microorganisms and helped BHB degradation. This is consistent with the
      observation that the biodegradation of BHB in native soil for 60 d reached > 60%.

PMID- 11337882
TI  - Ecotoxicological effects of hexahydro-1,3,5-trinitro-1,3,5-triazine on soil
      microbial activities.
AB  - Although hexahydro-1,3,5-trinitro-1,3,5-triazine (also called RDX or hexogen) is
      a potentially toxic explosive compound that persists in soil, its
      ecotoxicological effects on soil organisms have rarely been assessed. In this
      study, two uncontaminated garden soils were spiked with 10 to 12,500 mg RDX/kg
      dry soil. Soil microbial activities, i.e., potential nitrification, nitrogen
      fixation, dehydrogenase, basal respiration, and substrate-induced respiration
      were chosen as bioindicators and were determined after 1-, 4-, and 12-weeks of
      exposure. Experimental results indicate that RDX showed significant inhibition
      (up to 36% of control) on indigenous soil microbial communities over the period
      of this study. All five bioindicators responded similarly to the RDX challenge.
      The length of exposure also affected the microbial toxicity of RDX, with 12-week
      exposure exerting more significant effects than the shorter exposure periods,
      suggesting that soil microorganisms might become more vulnerable to RDX when
      exposure is extended. The estimated lowest observable adverse effect
      concentration of RDX was 1,235 mg/kg. No biodegradation products of RDX were
      detected at all three sampling times. Compared with 2,4,6-trinitrotoluene (TNT),
      RDX is less toxic to microbes, probably because of its resistance to
      biodegradation under aerobic conditions, which precludes metabolic activation of
      nitro groups.

PMID- 11337883
TI  - Partitioning of copper at concentrations below the marine water quality criteria.
AB  - Partitioning of Cu between the aqueous and particulate phases and among their
      components was examined in six ambient Puget Sound, Washington State, USA,
      samples (6-10 nM Cu). Most of the particulate Cu (4-12% of the total Cu) was
      associated with particulate organic matter, and resulted in distribution
      coefficients (Kd) ranging between 10(4.55) and 10(5.1). For the dissolved phase,
      the portion of Cu extracted by C18-packed cartridges averaged 44% (+11%).
      Radioactive 64Cu was added to these samples to total stable Cu concentrations (17
      33 nM). After 24 h of equilibration, the portion of 64Cu associated with the
      particulate matter in five of the six samples (Kd between 10(4.7) and 10(5.3) was
      an average of 70% higher than that of natural Cu in the ambient samples. In
      contrast, only 19 +/- 7% of the 64Cu was extracted by C18-packed cartridges. The
      partitioning of natural Cu and 64Cu onto particles was not significantly
      different when the equilibria were based on dissolved Cu passing through the C18
      cartridges. Further research is warranted on utilizing the hydrophilic component
      of the dissolved phase as a parameter on which water quality criteria are based.

PMID- 11337884
TI  - Isomeric effects on thiosulfate transformation and detoxification of 1,3
      dichloropropene.
AB  - The fumigant 1,3-dichloropropene (1,3-D) is one of the most heavily used
      pesticides but also a suspected carcinogen. Previous research has shown that 1,3
      D was rapidly transformed and detoxified by ammonium thiosulfate (ATS), a sulfur
      and nitrogen fertilizer. As common formulations contain cis and trans isomers at
      roughly equivalent ratios, this study was conducted to understand isomeric
      differences in thiosulfate transformation and detoxification of 1,3-D. Under the
      same conditions, reaction of cis-1,3-D with thiosulfate was more than three times
      faster than trans-1,3-D, which was correlated with a lower reaction activation
      energy for the cis isomer. The trans isomer was considerably more toxic to the
      luminescent bacteria Vibrio fisheri than the cis isomer, but the toxicity was
      reduced by 14 times after thiosulfate transformation. Mutagenic activity to
      strains of Salmonella typhimurium was observed for trans-1,3-D but was not
      detected after thiosulfate transformation. These results suggest that thiosulfate
      transformation detoxifies 1,3-D primarily by deactivating the trans isomer, and
      the reaction is toxicologically beneficial, as it negates the potential harmful
      effects of 1,3-D to the environment and human health.

PMID- 11337885
TI  - Potential of activated carbon to decrease 2,4,6-trinitrotoluene toxicity and
      accelerate soil decontamination.
AB  - Activated carbon can be used to decrease 2,4,6-trinitrotoluene (TNT) toxicity and
      promote bioremediation of highly contaminated soil. Adding activated carbon at
      0.25, 0.75, and 1.0% (w/w) to Sharpsburg soil contaminated with 500, 1,000, and
      2,000 mg TNT/kg decreased concentrations of TNT and its transformation products
      in soil solution to 5 mg/L or less, resulting in low toxicity to corn plants (Zea
      mays L.) and soil microorganisms. As much as 50% of the added TNT was rapidly
      bound to the soil-activated carbon matrix. Simultaneous accumulation of 2,4,6
      trinitrobenzaldehyde (TNBAld) indicated that the activated carbon promoted
      oxidation of TNT. Some of the TNBAld was further oxidized to 1,3,5
      trinitrobenzene, followed by reduction to 3,5-dinitroaniline. Reversibly bound
      TNT was gradually transformed to 2-amino-4,6-dinitrotoluene and 4-amino-2,6
      dinitrotoluene, and both were bound to the soil-activated carbon matrix. The
      transformation and binding of TNT to soil were further promoted by incorporating
      shredded corn plants after growing for 52 d in the activated carbon-amended soil.
      After 120 d, these amendments reduced extractable TNT and transformation products
      by 91% in soil containing 2,000 mg TNT/kg, compared to 55% in unamended soil.
      These results demonstrate the potential use of activated carbon in combination
      with plants to promote in situ bioremediation of soils highly contaminated with
      explosives.

PMID- 11337886
TI  - Abiotic processes influencing fipronil and desthiofipronil dissipation in
      California, USA, rice fields.
AB  - Fipronil insecticide dissipated in California rice fields, producing half-lives
      of 10.5 to 125 h in water and 44.5 to 533 h in soil, depending on the formulation
      applied and the resulting differences in water solubility. The major degradation
      products were desthiofipronil in water and fipronil-sulfide in soil, while the
      sulfone and amide were less abundant. Fipronil was photolyzed rapidly to
      desthiofipronil in deionized water in the laboratory (t1/2 = 7.97-9.42 h) and
      even faster in the presence of H2O2 (t1/2 = 0.874-4.51 h). Fipronil was also
      hydrolyzed to amide in base (t1/2 = 542 h at pH 9) and volatilized slowly from
      water (H = 6.60 x 10(-6) m3.atm/mol), properties not explaining its rapid field
      water dissipation. Desthiofipronil was more stable than fipronil to direct
      photolysis (t1/2 = 120-149 h), was indirectly photolyzed in the presence of H2O2
      (t1/2 = 0.853-3.76 h), and was nonvolatile from water. The desthiofipronil
      observed in field water was formed photochemically from fipronil, accumulated due
      to slower photolysis and lack of volatility from water, but eventually
      dissipated.

PMID- 11337887
TI  - Variations in heavy metal concentrations and speciation in two mining-polluted
      streams in central Norway.
AB  - The dissolved (dialysis in situ), colloidal (filtered minus dissolved), and total
      concentrations of Cu, Zn, Cd, and Al were determined and compared with pH, Ca
      concentrations, and alkalinities through seasonal variations in water levels in
      two streams, Rugla and Naustebekken, in the Roros area of central Norway. The
      main objective was to monitor the dissolved fraction of the metals during the
      seasons and to establish the extent to which chemical parameters influencing
      metal toxicity were unfavorable during episodes of high total metal
      concentrations. The average dissolved fractions of Cu, Zn, Cd, and Al were lower
      in Rugla (55, 69, 64, and 17%, respectively) compared with Naustebekken (59, 82,
      82, and 30%, respectively). This is probably due to sedimentation of metal
      particles in a small lake located in the path of Naustebekken. Alkalinity and Ca
      concentrations were generally low during the flood episodes, when the highest
      metal concentrations occurred. This is unfavorable since these parameters are
      assumed to counteract toxic effects of metals. On the other hand, the results
      indicate that toxic stress during metal concentration peaks was moderated by
      adsorption of dissolved metal species on colloids and/or particles.

PMID- 11337888
TI  - Identification and treatment of a waste stream at a bleached-kraft pulp mill that
      depresses a sex steroid in the mummichog (Fundulus heteroclitus).
AB  - Changes to indicators of reproductive performance have been documented in fish
      exposed to some bleached kraft pulp mill effluents (BKPMEs). However, responses
      are not consistent across mill types or processes. It is not clear where the
      sources of the effects are within mills, what the causative compounds are, or
      what process changes are effective to remove these sources. Our previous studies
      suggested that condensates were a source of compounds that reduced plasma
      testosterone in the mummichog (Fundulus heteroclitus). Results also suggested
      that reverse osmosis (RO) treatment of condensates removed this source. The
      objective of this study was to use a toxicity identification evaluation approach
      and expose mummichog to various waste streams in the laboratory to identify the
      effluent source that depressed plasma testosterone in the mummichog and the
      effects of RO treatment. In 7- and 21-d exposures, mummichog were exposed to
      dilutions of RO feed condensate, RO permeate, combined mill effluent (CME), and
      final effluent. Results confirmed that condensates depressed plasma testosterone
      in mummichog. Chemical characterization of the condensate indicated that plant
      phytosterols were likely not the responsible compounds. Results also confirmed
      that RO treatment removed the potential of the condensates to depress plasma
      testosterone in mummichog at environmentally relevant concentrations of final
      mill effluent (1%).

PMID- 11337889
TI  - Influence of salinity and eutrophication on bioaccumulation of 99technetium in
      duckweed.
AB  - This study concerns the bioaccumulation of the long-lived nuclear waste product
      99Tc in duckweed (Lemna minor L.). 99Tc was present as the oxyanion TcO4-, being
      the main chemical form of technetium in aerobic water systems. In contrast with
      terrestrial plants, bioaccumulation in duckweed proved to be independent of the
      nitrate concentration in the medium. However, uptake is controlled by
      electrostatic effects in the cell wall, which affects the bioaccumulation of 99Tc
      in duckweed in natural environments. These waters are characterized by a range of
      salinity and hardness, and this study suggests that this may result in up to a
      threefold difference in 99Tc accumulation. Because of screening of negative
      charges in the cell wall, the highest accumulation may be expected in hard,
      brackish water. This behavior can be described by a general model, which includes
      electrostatic effects and binding of cations at the cell wall. The model also
      explains why cationic radionuclides are preferably taken up in soft, fresh water
      while anionic species are concomitantly taken up in hard, chlorine-rich waters.

PMID- 11337890
TI  - Inositol lipids as spatial regulators of membrane traffic.

PMID- 11337891
TI  - Lipid-induced pore formation of the Bacillus thuringiensis Cry1Aa insecticidal
      toxin.
AB  - After activation, Bacillus thuringiensis (Bt) insecticidal toxin forms pores in
      larval midgut epithelial cell membranes, leading to host death. Although the
      crystal structure of the soluble form of Cry1Aa has been determined, the
      conformation of the pores and the mechanism of toxin interaction with and
      insertion into membranes are still not clear. Here we show that Cry1Aa
      spontaneously inserts into lipid mono- and bilayer membranes of appropriate
      compositions. Fourier Transform InfraRed spectroscopy (FTIR) indicates that
      insertion is accompanied by conformational changes characterized mainly by an
      unfolding of the beta-sheet domains. Moreover, Atomic Force Microscopy (AFM)
      imaging strongly suggests that the pores are composed of four subunits
      surrounding a 1.5 nm diameter central depression.

PMID- 11337892
TI  - Plasma membrane protein clusters appear in CFTR-expressing Xenopus laevis oocytes
      after cAMP stimulation.
AB  - Membrane trafficking of the cystic fibrosis transmembrane conductance regulator
      (CFTR) is supposed to be an important mechanism controlled by the intracellular
      messenger cAMP. This has been shown with fluorescence techniques, electron
      microscopy and membrane capacitance measurements. In order to visualize protein
      insertion we applied atomic force microscopy (AFM) to inside-out oriented plasma
      membrane patches of CFTR-expressing Xenopus laevis oocytes before and after cAMP
      stimulation. In a first step, oocytes injected with CFTR-cRNA were voltage
      clamped, verifying successful CFTR expression. Water-injected oocytes served as
      controls. Then, plasma membrane patches were excised, placed (inside out) on
      glass and scanned by AFM. Before cAMP-stimulation plasma membranes of both water
      injected and CFTR-expressing oocytes contained about 200 proteins per micron 2.
      Molecular protein masses were estimated from molecular volumes measured by AFM.
      Before cAMP-stimulation, protein distribution showed a peak value of 11 nm
      protein height corresponding to 475 kDa. During cAMP-stimulation with 1 mM
      isobutylmethylxanthine (IBMX) plasma membrane protein density increased in water
      injected oocytes to 700 proteins per micron 2 while the peak value shifted to 7
      nm protein height corresponding to 95 kDa. In contrast, CFTR-expressing oocytes
      showed after cAMP-stimulation about 400 proteins per micron 2 while protein
      distribution exhibited two peak values, one peak at 10 nm protein height
      corresponding to 275 kDa and another one at 14 nm corresponding to 750 kDa. They
      could represent heteromeric protein clusters associated with CFTR. In conclusion,
      we visualized plasma membrane protein insertion upon cAMP-stimulation and
      quantified protein distribution with AFM at molecular level. We propose that CFTR
      causes clustering of plasma membrane proteins.

PMID- 11337893
TI  - Sequential amino acid exchange across b(0,+)-like system in chicken brush border
      jejunum.
AB  - In the small intestine, cationic amino acids are transported by y(+)-like and
      b(0,+)-like systems present in the luminal side of the epithelium. Here, we
      report the characterization of a b(0,+)-like system in the apical membrane of the
      chicken jejunum, and its properties as an amino acid exchanger. Analysis of the
      brush border membrane by Western blot points out the presence of rBAT (protein
      related to b0,+ amino acid transport system) in these membranes. A functional
      mechanism for amino acid exchange across this system was established by kinetic
      analysis measuring fluxes at varying substrate concentrations both in internal
      (in) and external (out) vesicle compartments. This intestinal b(0,+)-like system
      functions for L-arginine as an obligatory exchanger since its transport capacity
      increases 100-200 fold in exchange conditions, thus suggesting an important role
      in the intestinal absorption of cationic amino acids. The kinetic analysis of
      Argin efflux velocities is compatible with the formation of a ternary complex and
      excludes a model involving a ping-pong mechanism. The binding affinity of Argout
      is higher than that of Argin, suggesting a possible order of binding (Argout
      first) for the formation of the ternary complex during the exchange cycle. A
      model of double translocation pathways with alternating access is discussed.

PMID- 11337894
TI  - Look again: research, uncertainty, and understanding.

PMID- 11337895
TI  - College smoking policies and smoking cessation programs: results of a survey of
      college health center directors.
AB  - College students' cigarette smoking rose dramatically during the 1990s. Little is
      known about what colleges do to address the problem. Health center directors at
      393 4-year US colleges provided information (response rate: 65.1%) about college
      policies addressing smoking and the availability of smoking cessations programs.
      Of the health center directors surveyed, 85% considered students' smoking a
      problem; yet only 81% of colleges prohibit smoking in all public areas and only
      27% ban smoking in all indoor areas, including students' rooms in dormitories and
      in private offices. More than 40% of the respondents reported that their schools
      did not offer smoking cessation programs and that the demand for existing program
      was low. Colleges need to do more to discourage student tobacco use. Recommended
      actions include campus-wide no-smoking policies that apply to student residences
      and identification of new ways of providing smoking prevention and cessation
      services.

PMID- 11337896
TI  - Trial and lifetime smoking risks among African American college students.
AB  - The authors surveyed 614 African American university students to determine the
      magnitude of cigarette use, identify risk factors, and develop models to predict
      smoking. More than half (58.3%) of the participants had smoked at least once, and
      9.3% of that group were lifetime smokers. Among the lifetime smokers, 71.3% had
      smoked during the 30 days preceding the survey. More women (66.8%) than men
      (56.1%) had tried smoking and were classed as lifetime smokers. Residence,
      parental, and peer smoking (current and childhood) were associated with trying
      smoking; age, race/ethnicity, and marital status were additional factors for
      becoming a lifetime smoker. The risk of being a lifetime smoker was reduced when
      neither friends nor parents of the student smoked and the student viewed
      spirituality as important. The results of this study add to the growing
      understanding of health risk behaviors among African Americans and can be useful
      in reducing smoking.

PMID- 11337897
TI  - US college students' reports of receiving health information on college campuses.
AB  - Institutions of higher education are in a unique position to promote healthy
      behaviors by providing health education to students, but little information
      exists about the proportion of students reached by such efforts. The authors used
      data from a nationally representative sample of college students to describe the
      extent to which students reported receiving health information from their
      colleges and universities, to examine the characteristics of students who
      received such information, and to determine specific sources of health
      information. Approximately three quarters of college students reported they
      received information on at least one health topic, and 6% received information on
      all of the topics examined. Those who reported receiving health information from
      their colleges or universities were likely to be "traditional" college students.
      To achieve relevant national health objectives, health educators must increase
      the proportion of students they reach and the number of health topics they cover.

PMID- 11337898
TI  - Disordered eating in college freshman women: a prospective study.
AB  - The authors assessed eating behaviors and attitudes of 225 college freshman women
      on the bulimia and restraint scales at the beginning of the year. Seven months
      later, they reassessed 104 of the original students. Concurrent data regression
      analyses found that symptoms of eating pathology were associated with figure
      dissatisfaction, ineffectiveness, public self-consciousness, and vigor on the
      Profile of Mood States, and for bulimia, self-efficacy to control eating when
      experiencing negative feelings, and reward conditions. Both bulimia and restraint
      were highly stable across the 7 months. Prospective analyses, controlling for the
      initial level of eating pathology in hierarchical regressions, found that figure
      dissatisfaction, ineffectiveness, and alcohol use/abuse over the past year were
      significant predictors of worsening symptoms. Beginning levels of bulimia and
      restraint were the best predictors of eating pathology at the end of the study.
      The roles that self-image and alcohol use may play as vulnerabilities for eating
      pathology are also considered.

PMID- 11337899
TI  - Out of harmony: health problems and young Native American men.
AB  - Studies of the current health status of healthy young Native American men
      (American Indians and Alaska Natives) are rare compared with the attention
      researchers have given the many problems that plague the lives of these young
      men. Native American men are frequently not included in other studies focusing on
      men, and information on college-aged, healthy young Native American men is
      generally not readily available. Despite those drawbacks, this article brings
      together what is written or known about the health status of young Native
      American men. The emphasis, based on available information, is placed on some of
      the major health problems confronting this population.

PMID- 11337900
TI  - Assessing binge drinking: what you get is what you ... ask!

PMID- 11337901
TI  - Utility of intra-operative consultations for the diagnosis of central nervous
      system lesions.
AB  - The inherent soft nature of the central nervous system (CNS) renders poor-quality
      frozen sections. Cytology has been shown to be of great value in intra-operative
      consultations of CNS pathology. The current study was undertaken to examine the
      utility of intra-operative consultations regarding CNS lesions, comparing the
      usefulness and limitations of frozen section and cytology techniques. A
      retrospective study of 103 cases of CNS intra-operative consultations was
      performed. Concordance between the intra-operative diagnosis and the final
      diagnosis was seen in 94% of cases. Most discrepancies were due to failure to
      recognize atypia in meningiomas. The cytology technique was more useful for
      astrocytomas, small round cell tumors, and certain metastases. The frozen section
      technique was better for the diagnosis of meningiomas, reactive lesions,
      ependymomas, and most metastatic lesions. Using a combination of the two
      techniques is most beneficial.

PMID- 11337902
TI  - Proximal myotonic myopathy: clinical, neuropathologic, and molecular genetic
      features.
AB  - The primary genetic abnormality in myotonic dystrophy (DM) is an expansion of the
      CTG trinucleotide repeat on chromosome 19q. Recently, patients with similar
      clinical features, but without this genetic alteration, have been designated as
      proximal myotonic myopathy (PROMM). We describe two additional cases of PROMM,
      both of whom presented with clinical features suggestive of myotonic dystrophy.
      The patients had electromyographic (EMG) evidence of myotonia, normal cardiac
      evaluation, and no cataracts. Genetic analysis of peripheral blood leukocytes
      revealed no expansion of the trinucleotide repeat by polymerase chain reaction
      (PCR) and Southern blot analysis. Muscle biopsies in both cases were significant
      with features suggestive of myotonic dystrophy, such as large numbers of fibers
      containing multiple internal nuclei, occasional nuclear chains, and fiber
      atrophy, although sarcoplasmic masses and ring fibers were absent. These cases
      illustrate the clinical and neuropathologic findings of PROMM and underline the
      importance of correlating these aspects with genetic studies in patients with
      myotonic muscle disorders.

PMID- 11337903
TI  - Concurrent malakoplakia and papillary urothelial carcinoma of the urinary
      bladder.
AB  - A case of malakoplakia and papillary urothelial carcinoma of the urinary bladder
      is reported. In this case, malakoplakia was an incidental finding in a biopsy of
      the urinary bladder of a 74-yr old female, who presented with hematuria. The
      biopsy showed a low-grade papillary urothelial carcinoma in close association
      with malakoplakia. This is a rare association of these lesions.

PMID- 11337904
TI  - Changes in serum lipid concentrations during iron depletion and after iron
      supplementation.
AB  - To investigate the effects of body iron depletion and iron supplementation on
      serum lipid concentrations, hematologic indices, iron markers, and serum lipid
      profiles were measured in 427 girls, age 14-19 yr. There were no significant
      differences in serum lipid concentrations between subjects with moderate iron
      deficiency anemia (blood Hb < 12.0 g/dL) and healthy controls. However, serum
      total cholesterol concentration (mean +/- SD, 148 +/- 16 mg/dL) in severely
      anemic subjects with blood Hb < 8.0 g/dL was significantly lower than in subjects
      with blood Hb > or = 14.0 g/dL (170 +/- 17 mg/dL) (p < 0.01). Moreover, serum
      triglyceride concentration in subjects with blood Hb > 14.0 g/dL was 2-fold
      higher than in the severely anemic subjects. Mean values of serum total
      cholesterol and triglyceride (149 +/- 17 mg/dL and 58 +/- 22 mg/dL) in girls with
      severe anemia were significantly elevated after iron supplementation (164 +/- 17
      mg/dL and 98 +/- 26 mg/dL) (p < 0.01, respectively). In the severely anemic
      subjects, blood Hb concentration was correlated with serum total cholesterol (r =
      0.49, p < 0.01) and triglyceride concentrations (r = 0.51, p < 0.01). These
      findings indicate that severe iron deficiency anemia in girls is attended by
      decreased concentrations of serum total cholesterol and triglyceride, and that
      these reduced serum lipid levels return to normal following iron supplementation.

PMID- 11337905
TI  - Cytomegalovirus seropositivity and serum total cholesterol levels in young
      patients.
AB  - Atherosclerosis is a chronic inflammatory disease of arteries, associated with
      multiple genetic and environmental factors, including hypertension, diabetes
      mellitus, cigarette smoking, modified and elevated LDL cholesterol, elevated
      plasma homocysteine, and infectious microorganisms such as Chlamydia pneumoniae
      and cytomegalovirus (CMV). CMV has been implicated in atherogenesis by
      epidemiological studies, animal research, and molecular analyses that have
      demonstrated CMV nucleic acids within human atherosclerotic lesions. Studies have
      suggested that CMV infection may alter lipid metabolism and lead to accumulation
      of cholesterol within atheromatous plaques. Few studies have examined the
      relationship between CMV infection and serum cholesterol levels in younger
      individuals when much of atherogenesis occurs. To test if CMV-seropositivity is
      associated with high levels of serum total cholesterol in relatively young
      patients, CMV IgG levels and total cholesterol concentrations were analyzed in
      serums from 172 patients, age < 50 yr. Based on univariate analysis of variance,
      serum total cholesterol was significantly correlated to age and to CMV
      seropositivity when gender was a cofactor, but not to gender or CMV
      seropositivity alone. In 39 CMV-seropositive women, serum total cholesterol
      concentration averaged 218 +/- 50 mg/dL (mean +/- SD), which was significantly
      higher than in 53 CMV-seronegative women (194 +/- 39 mg/dL, p < 0.02). No
      significant difference was observed between the serum total cholesterol
      concentrations in 26 CMV-seropositive men and 51 CMV-seronegative men (198 +/- 42
      mg/dL versus 212 +/- 48 mg/dl, respectively). Thus, this study provides evidence
      that CMV-seropositivity is associated with higher serum total cholesterol levels
      in female patients under 50 yr of age, but not in male patients of comparable
      age.

PMID- 11337906
TI  - Characterization of an apolipoprotein E3 variant (Arg 145-->His) associated with
      mild hypertriglyceridemia.
AB  - In a proband (21-yr-old female), we previously identified an apolipoprotein (apo)
      E variant, apoE3 (Arg 145-->His), with an isoelectric point midway between apoE3
      and apoE2. ApoE gene analysis of 4 of the proband's kin indicated that 3 possess
      the same variant. All 4 had a high concentration of apoE in plasma, while 3 of 4
      had hypertriglyceridemia. In the proband (who had no hypertriglyceridemia), most
      apoE was distributed in slow-alpha lipoproteins (predominantly in the form of
      apoE-AII heterodimer) and in larger molecules with apparent molecular weights of
      80 and 100 kDa. In the proband's brother (with hypertriglyceridemia), however,
      most apoE was distributed in slow pre-beta lipoproteins, predominantly in the
      form of monomeric apoE. In each subject, the concentration of apoE3 variant was
      significantly higher than that of normal apoE3 in the predominant apoE-rich
      lipoprotein. The apoE3 variant, which displayed a slightly reduced binding
      ability to LDL-receptor and heparin, may induce an accumulation of apoE-rich
      lipoproteins. These observations suggest that the difference in distribution of
      apoE3 variant in plasma lipoproteins between the proband and her brother
      (combined with its reduced affinity for the LDL receptor) may provide key
      insights into the pathogenesis of hypertriglyceridemia.

PMID- 11337907
TI  - Search for immunomodulatory effects of blood transfusion in gastric cancer
      patients: flow cytometry of Th1/Th2 cells in peripheral blood.
AB  - Allogeneic transfusion seems to drive the immune system toward a Th2 response and
      away from a Th1 response, providing a hypothetical mechanism for transfusion
      induced immunomodulation. By means of an intracytoplasmic cytokine detection
      technique with flow cytometry, it is possible to measure Th1 and Th2 cells
      derived from peripheral blood mononuclear cells. This study evaluated the
      presence of transfusion-induced immunomodulation in 11 gastric cancer patients
      after gastrectomy with perioperative blood transfusion, compared to 11 gastric
      cancer patients who were treated by gastrectomy without transfusion. Lymphocytes
      subsets, including CD4 T cells, CD8 T cells, CD4/CD8 Ratio, CD2(+) T cells,
      CD3(+) T cells, and CD19(+) B cells, were measured in these patients, as well as
      variables that might suggest transfusion-induced immunomodulation, such as
      duration of antibiotic use, duration of hospital stay, and total hospital
      charges. This study also measured changes in the Th1/Th2 ratio. Th1 and Th2
      lymphocytes were characterized by measuring intracellular expression of cytokines
      with flow cytometry. Cells were stimulated with phorbol myristate acetate and
      ionomycin in the presence of brefeldin-A. The results showed no significant
      differences in lymphocyte subsets, Th1/Th2 ratio, total hospital charges, or
      duration of antibiotic utilization between the groups of transfused and non
      transfused gastric cancer patients after gastrectomy. The only significant
      difference was a longer hospital stay for transfused patients (mean 20.5 da)
      compared to non-transfused patients (mean 16.2 da). The anticipated finding of a
      Th2 response after blood transfusion was not observed. A larger group of patients
      may be needed to document such an effect, since many confounding variables affect
      the morbidity and outcome of surgery in these patients.

PMID- 11337908
TI  - Endothelial nitric oxide synthase (eNOS) expression and localization in healthy
      and diabetic rat hearts.
AB  - Several studies suggest that nitric oxide (NO) production is reduced in diabetes
      and that the decrease of NO may be related to the pathogenesis of diabetic
      endothelial damage. NO synthase (NOS) catalyses the conversion of L-arginine to L
      citrulline in the presence of oxygen and NADPH-diaphorase (NADPH-d). In this
      study, we evaluated the expression of endothelial NOS (eNOS) enzyme and its co
      enzyme in diabetic rat hearts. Male Wistar rats (n = 20, 4 mo old) and 20 male
      Bio Breeding Wistar (BB/W) rats of the same age were used; the Wistar rats
      represent the control non-diabetic rats while the BB/W rats represent the
      diabetic group. After the hearts were excised, the NADPH-d co-enzyme was
      visualized by a histochemical method and the endothelial isoform of NOS was
      localized by immunohistochemistry. In addition, eNOS gene expression was
      estimated by rt-PCR, and eNOS protein level was detected by Western blot
      analysis. The eNOS visualization, which involved immunoprecipitation, and the
      NADPH-d visualization, which involved histochemical staining, were both
      diminished in endothelial cells of the vascular wall of diabetic hearts, compared
      to non-diabetic hearts. The eNOS protein level, evaluated by Western blotting,
      was evident as an intense band in cardiac homogenates of non-diabetic and
      diabetic rats. The expression of mRNA for eNOS did not differ significantly
      between the two groups. These findings indicate that, in this rat heart model,
      diabetes does not influence the overall eNOS protein level or its mRNA level.
      However, there a diminution in the deposition of eNOS in cardiac endothelial
      cells of diabetic rats, versus non-diabetic controls, suggesting a relation
      between eNOS and the loss of vasodilatory response that is observed in diabetes.

PMID- 11337909
TI  - Hoechst 33342-induced apoptosis is associated with decreased immunoreactive
      topoisomerase I and topoisomerase I-DNA complex formation.
AB  - Hoechst 33342, but not Hoechst 33258, induces apoptosis and inhibits
      topoisomerase 1 activity in vivo. Topoisomerase I relaxes superhelical DNA
      through a single strand breakage/rejoining reaction in which the active site
      tyrosine links covalently to a 3' phosphate at the break site, forming a
      transient intermediate called a cleavable complex. The fate of cellular
      topoisomerase 1 in Hoechst 33342-induced apoptosis is unknown. We analyzed the
      binding capacity of topoisomerase 1 to 32P-labeled plasmid pCI DNA, the
      immunoreactive topoisomerase 1 concentration and topoisomerase 1 activity in BC3H
      1 myocytes and HL-60 cells treated with Hoechst 33342 and Hoechst 33258 by using
      covalent transfer of 32P radioactivity from plasmid DNA to topoisomerase 1,
      Western blotting and topoisomerase 1-mediated plasmid relaxation assay,
      respectively. Hoechst 33342, but not Hoechst 33258, induced topoisomerase 1
      dysfunction in both BC3H-1 myocytes and HL-60 cells measured by (1) a decrease in
      the topoisomerase 1 to DNA binding capacity or cleavable complex formation; (2) a
      decrease in intracellular concentration of immunoreactive topoisomerase 1; and
      (3) an inhibition of nuclear endogenous topoisomerase 1 activity. These results
      suggest that destruction of immunoreactive topoisomerase 1 and topoisomerase 1
      DNA complexes or cleavable complexes results in inhibition of topoisomerase 1
      activity, a key step in the Hoechst 33342-induced apoptotic process.

PMID- 11337910
TI  - Diagnosis of adrenal cortical dysfunction by liquid chromatography-tandem mass
      spectrometry.
AB  - Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to measure 6
      metabolic compounds of the adrenocorticosteroid pathway simultaneously on
      residual specimens from patients who had previously been previously diagnosed, on
      the basis of immunoassays, as having congenital adrenal hyperplasia (CAH), 11
      beta-hydroxylase deficiency, 21-hydroxylase deficiency, or Addison disease
      (adrenal insufficiency). Two subjects with normal adrenal function had serum
      cortisol values of 13.6 and 8.9 micrograms/dL and serum cortisone values of 2.1
      and 0.6 microgram/dL, but the rest of the compounds were undetectable. Two
      patients with 11 beta-hydroxylase deficiency had serum 11 beta-deoxycortisol
      values of 14.9 and 10.0 micrograms/dL and serum 11-deoxycorticosterone values of
      3.9 and 1.0 microgram/dL, but their serum levels of cortisol and cortisone were
      diminished. A patient with 21-hydroxylase deficiency had a highly increased serum
      17-hydroxyprogesterone concentration of 28.5 micrograms/dL (or 28,500 ng/dL, the
      traditional unit to report this assay) and a serum 21-deoxycortisol concentration
      of 6.9 ug/dL (this is a pathologic marker of 21-hydroxylase deficiency that is
      nondetectable in sera of healthy subjects). This patient also had diminished
      concentrations of serum cortisol and cortisone (0.9 and 0.3 microgram/dL,
      respectively). At 30 and 60 min after corticotropin (ACTH) stimulation, serum
      cortisol was the only compound that showed a dramatic increase in the normal
      subjects; the patient with 21-hydroxylase deficiency showed an increase of serum
      17-hydroxyprogesterone level, but no increase of serum cortisol level; the
      patient with Addison disease showed no increase in the levels of serum cortisol
      or other compounds. Metyprapone, which blocks 11 beta-hydroxylase activity,
      increased the serum 11-deoxycorticosteroid levels and decreased the serum
      cortisol level. This pilot study demonstrates that it is feasible to use LC-MS/MS
      for the laboratory diagnosis of adrenal cortical dysfunction. The authors
      envision that LC-MS/MS may soon become an ideal analytical technique for the
      diagnosis of such endocrine diseases.

PMID- 11337911
TI  - Use of microtiter plates for latex agglutination immunoassay of serum alpha 2
      macroglobulin.
AB  - A simple, sensitive turbidimetric immunoassay is described for analysis of alpha
      2-macroglobulin (AMG) in serum, using microtiter plates and a commercial kit that
      features a sensitive latex reagent. Using microwells as reaction vessels and the
      latex reagent made it possible to minimize the sample size and the amounts of
      reagents. The procedure involves two pipetting steps and a brief incubation (10
      min) at room temperature; the assay measures AMG concentrations ranging from 0.12
      to 5 g/L and is unaffected by icterus, hemolysis, lipemia, or rheumatoid factor,
      even at high concentrations. Recovery of AMG added to three pooled serum samples
      averaged 95-105%. CVs for replicate analyses ranged from 1.9 to 4.8% (within-run)
      and 6.1 to 9.3% (between-run). Based on paired analyses of 70 serum specimens,
      AMG concentrations obtained by this turbidimetric microtiter immunoassay were in
      close agreement (correlation coefficient = 0.99) with results obtained by an
      enzyme-linked immunosorbent assay (ELISA). Serum AMG concentrations in 48 healthy
      adults (mean +/- 2SD) were 1.87 +/- 1.00 g/L.

PMID- 11337912
TI  - A cluster of Creutzfeldt-Jacob disease patients from Nassau County, New York,
      USA.

PMID- 11337913
TI  - [Intradermal tests using vasomotor agents in allergic rhinitis].
AB  - INTRODUCTION: Allergic rhinitis is characterised by nasal hyperactivity to
      specific and non-specific agents. For research purposes, non-specific nasal
      hyperactivity can be estimated by histamine and metacholine nasal challenge
      tests. At present, nasal challenge tests are not used for routine diagnosis of
      rhinitis. Wayoff and colleagues proposed the examination of the skin reactivity
      to papaverine, acetylcholine, histamine and compound 48/80 in rhinitis patients.
      Our previous study of skin reactivity to vasomotor agents, using modified skin
      tests of Wayoff and colleagues showed their clinical validation and usefulness
      for subclassification of patients with non-allergic rhinitis. To the present,
      there are only a few studies of skin reactivity to vasomotor agents in patients
      with allergic rhinitis. The aim of this study was to examine the skin reactivity
      to vasomotor agents of allergic rhinitis patients and determine whether the
      patients with allergic rhinitis differ from healthy subjects. METHODS: A
      prospective, controlled, in vivo study was carried out in 86 subjects: 44
      patients with allergic rhinitis and 42 healthy subjects. Skin reactivity was
      examined by intradermal tests with different concentrations of papaverine,
      metacholine, histamine and compound 48/48. The non-specific skin reactivity to
      saline was also measured. Skin reactivity to intradermal test with different
      concentrations of papaverine, metacholine, histamine and compound 48/48 was
      measured, as well as specific skin reactivity to control saline solution.
      Pathological skin reactivity to vasomotor agents was defined as follows:
      hyporeactivity to papaverine (5 mg/mL), when wheal-and-flare skin reaction
      diameter was less than 15 mm; hyper-reactivity to metacholine (0.02, 0.2 and 2.0
      mg/mL), when two of three wheal-and-flare skin reaction diameters were greater
      than 15, 25 and 31 mm, respectively; hyper-reactivity to histamine (0.01, 0.1,
      1.0 and 10.0 mg/mL), when three of four wheal-and-flare skin reaction diameters
      were greater than 7, 13, 25 and 40 mm, respectively; and hyper-reactivity to
      compound 48/80 (0.01, 0.1, 1.0 and 10.0 mg/mL), when three of four wheal-and
      flare skin reaction diameters were greater than 9, 16, 26 and 38 mm,
      respectively. RESULTS: The study included 86 subjects: 44 patients with allergic
      rhinitis and 42 healthy subjects. The control group of healthy subjects consisted
      of 22 females, aged from 18 to 35 yrs (mean 28 yrs), and 20 males, aged from 18
      to 40 yrs (mean 28 yrs). The difference between the number [p(= 0.758) > 0.05]
      and age [p(= 0.990) > 0.05] of females and males was not significant. In the
      allergic rhinitis patients group, there were 23 females, aged from 18 to 54 yrs
      (mean 33 yrs) and 21 males, aged from 18 to 50 yrs (mean 36 yrs). The difference
      between the number [p(= 0.763) > 0.05] and age [p(= 0.558) > 0.05] of females and
      males was not significant. Frequencies of pathological skin reactivity to single
      vasomotor agents and saline in the control group of healthy subjects and in the
      allergic rhinitis patients group are shown in Table 1. In the control group,
      frequencies of normal skin reactivity to papaverine [p(= 1.8 x 10(-7)) < 0.01],
      metacholine [p(= 4.3 x 10(-6)) < 0.01], histamine [p(= 4.3 x 10(-6)) < 0.01],
      compound 48/80 [p(= 1.8 x 10(-7) < 0.01] and saline [p(= 6.9 x 10(-4)) < 0.01]
      were significantly greater than frequencies of pathological skin reactivity. In
      the patients group, frequencies of normal skin reactivity to papaverine [p(= 6.0
      x 10(-8)) < 0.01] and saline [p(= 2.6 x 10(-3) < 0.01] were significantly
      greater, and to metacholine [p(= 0.016) < 0.05] were significantly greater than
      frequencies of pathological skin reactivity. In this group, the difference
      between frequencies of pathological skin reactivity to histamine [p(= 0.366) >
      0.05] and compound 48/80 [p(= 0.070) > 0.05] were not significant. There was no
      significant intergroup difference for pathological skin reactivity to papaverine,
      metacholine and saline (Table 1). In the patients group frequencies of
      pathological skin reactivity to histamine and compound 48/80 were significantly
      higher than in the control group of healthy subjects. Frequencies of pathological
      skin reactivity to single vasomotor agents and in combinations in the control
      group of healthy subjects and in the allergic rhinitis patients group are shown
      in Table 2. The difference of pathological skin reactivity to single vasomotor
      agents and in combinations between the control group (14/42) and the allergic
      rhinitis patients group (27/44) was significant [p(= 0.017) < 0.05]. CONCLUSION:
      In routine evaluation of the rhinitis patients, skin tests with vasomotor agents
      have some advantages: these tests do not require special equipment, they are not
      time-consuming, they are easy to perform and simple for the interpretation of
      results. (ABSTRACT TRUNCATED)

PMID- 11337914
TI  - [20 years' experience in the treatment of children with terminal renal
      insufficiency in Yugoslavia].
AB  - The first specialized haemodialysis (HD) paediatric centre in former Yugoslavia
      was established at the University Children's Hospital in Belgrade in January
      1980. A total of 194 children (F: 98, M: 96), aged less than 19 years (10.12 +/-
      4.23), were treated for renal replacement therapy (RRT) over 20 years. Average
      annual incidence rate was 1.59 per million of child population (pmcp) aged less
      than 19 years for the period 1980-1990 (former Yugoslavia) and 2.85 pmcp aged
      less than 19 years for the period 1990-2000 (present Yugoslavia). Reflux
      nephropathy was the most frequent underlying disease and accounted for 37.06% of
      total cases, while other primary renal diseases were: glomerulonephritis (GN)
      17.26%, cystic/hereditary familial nephropathy 12.69%, congenital disease 11.68%,
      interstitial nephritis 5.58%, non-recovered tubular necrosis 3.55%, secondary GN
      1.52% and 10.66% remained with doubtful diagnosis. HD was the first RRT in
      84.02%, peritoneal dialysis (PD) in 14.43% and pre-emptive transplantation in
      1.55% of all patients. A total of 53 patients (27.3% of total terminal renal
      failure (TRF) patients) received 56 kidney transplants (58.93% live related,
      37.50% cadaveric, 3.57% live-non related). Actual survival in RRT was 64.53% 5 in
      years; 51.68% in 10 and 48.23% in 15 years. Patient survival in HD was
      significantly better over the last ten-year period than in the first ten-year
      period (35.88% vs. 75.75%; p < 0.005) as well as the survival of transplanted
      patients in the same two periods (67.62% vs. 95.45%). Graft survival was 79.85%
      in 5 and 70.50% in 10 years. Cardiovascular complications were the most common
      cause of death of patients on RRT (56.10 posto) followed by infection (24.39). On
      December 31, 1999, 54 patients on RRT were alive less than 19 years: 75.92% in
      HD; 22.22% with functioning graft and 1.85% on automatic PD. This is the first
      national-wide long-term study of incidence and aetiology of paediatric TRF and
      outcome of paediatric RRT in Yugoslavia.

PMID- 11337915
TI  - [Detection of human papillomaviruses in cervical intraepithelial neoplasms].
AB  - Over the period 1994-1998 1000 patients suffering from intraepithelial cervical
      lesions (SIL) were examined for the presence of Human Papilloma Virus (HPV)
      infection. Today it is completely acknowledged that certain types of these
      viruses play a key role in the onset and evolution of these diseases. The study
      showed that SIL of the cervix appears in very young women. The highest incidence
      was found in age groups 24-28 years (21.10%) and 29-33 years (19.10%). Thus, over
      40% of the entire study group patients was under 34 years of age. Histological
      analysis of tissue samples showed that 79.30% of patients had lesions of low
      histological grade (LSIL), while in 20.70% of them the disease progressed to a
      high histological level (HSIL). Detection of Human Papilloma Virus Infection
      revealed negative results in 34.90% of patients, 17.80% were 6/11 positive (non
      oncogenic type), and in 47.30% oncogenic types were found (16, 18, 31, 33). This
      finding in the LSIL group was exceptionally important since it influenced the
      approach to treatment. Oncogenic types of viruses were detected in 34.30% of LSIL
      lesions; it indicates a high progression potential of pathological changes.

PMID- 11337917
TI  - [Cardiovascular manifestations of hyperthyroidism. Clinical significance and
      preoperative preparation].
AB  - More than 200 years ago, Caleb Parry described cardiological manifestations of
      hyperthyroidism. Interaction of thyroid hormones and sympathoadrenal system
      (responsible for rhythm disorders) and direct effect of thyroid hormones on the
      cardiac muscle (responsible for occurrence of hypertrophy and cardiac
      insufficiency) have been recognized as the pathophysiological basis of
      cardiovascular disorders of patients with hyperthyroidism. The aim of the study
      was to retrospectively analyze surgically treated patients with different types
      of hyperthyreosis, and establish the incidence and clinical significance of the
      left ventricular dysfunction related to duration and treatment of hyperthyreosis.
      Evaluation of left ventricular function was based on the ejection fraction during
      exercise. Signs of hypertrophy were echocardiographically, radiographically and
      electrocardiographicaly recorded. Over the period 1993-1997 at the Surgical
      Department of the institute of Endocrinology in Belgrade 423 patients with
      hyperthyreosis were operated: 293 (69.26%) patients had Graves-Basedow's disease,
      74 (17.49%) toxic adenoma, and 58 (13.28%) toxic polynodal struma. The average
      duration of the disease in patients with Graves-Basedow's hyperthyreosis was 5
      yrs, and the average age of patients was 29 yrs; the average duration of
      hyperthyreosis in patients with toxic adenoma was 1.2 yrs, and in cases of toxic
      polynodal struma 17 yrs. Pathological response of ejection fraction during
      exercise was recorded in 60% of patients. Signs of hypertrophy of the left
      chamber were recorded in 17% of subjects, and insufficiency of the left chamber
      with congestive stasis in the lungs in 4.6% of patients. The most common ECG
      changes were: synus tachycardia, higher voltage of P and T waves, elevated
      amplitude of QRS complex, prolonged P-Q and shortened Q-T intervals. In 20% of
      cases atrial fibrillation was evidenced. One patient had ECG signs of myocardial
      infarction. Clinical features of left ventricular dysfunction in hyperthyroidism
      include: occurrence in younger patients with history of hyperthyroidism,
      progressive course and occurrence of congestive cardiac failure as well as
      reversible nature of all cardiac changes after radical therapy of hyperthyreosis
      which can be medical, surgical or irradiation.

PMID- 11337916
TI  - [Effect of certain aspects of female sexual behavior on the development of
      cervical intraepithelial neoplasia].
AB  - The paper presents results of investigation of certain parameters of female
      sexual activity and their effect on the appearance of squamous intraepithelial
      cervical lesions (SIL). This correlation was investigated in the context of Human
      Papilloma Virus (HPV) infection, in view of the role attributed to certain types
      of these viruses in the appearance and development of cervical SIL. Research was
      done on 1000 patients suffering from low histological grade (LSIL) or high
      histological grade (HSIL) intraepithelial cervical neoplasms. It transpired that
      such lesions were most frequent in women in the second, third and fourth decade
      of life, and that one third of pathological lesions was a function of age. Human
      Papilloma Virus infection was detected in 65% of patients. The frequency of HPV
      negative results or presence of non-oncogenic types of viruses (6 and 11) was
      significantly higher in LSIL type lesions, while the frequency of detection of
      oncogenous HPV types (16, 18, 31 and 33) was significantly higher in more severe
      stadiums of the disease. Of the investigated parameters of sexual activity, early
      onset of such activity and several sexual partners proved to be significant. The
      number of parturitions and abortions did not appear to be significant risk
      factors for the onset and development of these diseases.

PMID- 11337918
TI  - [Role of wrist instability in the onset of pseudoarthrosis of the scaphoid bone].
AB  - INTRODUCTION: The most common fracture involving the wrist is a fracture of the
      scaphoid bone. Fracture of the scaphoid most frequently occurs in young adult
      male and usually involves the wrist of the scaphoid. There is a universal
      agreement that the majority of these fractures will heal if immobilized property
      and for a long period of time [1, 2]. In the treatment of these fractures much
      attention has been payed to bone damage and not to associated ligament injury. It
      is reported that the incidence of nonunion of scaphoid fractures is ten per cent
      and that the frequency of this complication remains essentially unchanged [3, 4].
      Failure to improve the outcome suggests that the mechanisms and causes of this
      complication are poorly understood. Explanations of nonunion or delayed union of
      scaphoid bone are: poor initial treatment or even no treatment [3], delayed
      diagnosis [5], fragments displacement [5-8], improper immobilization [9], site
      and direction of the fracture [3] and wrist instability [8, 10]. AIM: The study
      was undertaken to analyse the influence of carpal instability on the development
      of scaphoid nonunion. METHOD: The study concerned 40 patients with painful
      nonunions of the scaphoid bone. Duration of nonunion was 1.43 year. There were 37
      (92%) male and 3 (8%) female patients. Site and direction of the fracture,
      initial treatment and carpal collaps were analysed. Data processing was done for
      all examined patients (Table 1). RESULTS: Dominant hand was involved in 24 (60%)
      patients and nondominant hand in 16 (40%) subjects. Carpal collaps was present in
      68% of patients. There were 14 (35%) untreated patients (Graph 1). Untreated
      fractures were statistically insignificant regarding the intensity of carpal
      collaps (p = 0.101; p > 0.05). The physical examination usually revealed focal
      tenderness, a palpable click with ulnar deviation, abnormal antero-posterior
      mobility with passive range of motion or a combination of these findings.
      Standard X-rays evaluated fracture location and carpal instability or collaps.
      There were 14 (35%) proximal third located fractures and 26 (65%) in the middle
      third of wrist (Graph 2). There was no statistically significant correlation
      between location of the fracture and presence of carpal collaps (p = 0.081; p >
      0.05). DISCUSSION: There were 35 per cent overlooked fractures. Delay in
      diagnosis of a scaphoid fracture has been suggested as a significant factor in
      the development of nonunion [5, 7]. However, in our series of nonunions, non
      treatment does not occur frequently enough to be the critical factor. Most series
      report about 2/3 of nonunions occurring at the wrist [7, 9]. Our series shows a
      similar distribution, arguing against site as a critical factor. There appears to
      be a nearly uniform rate of nonunion in most of the reported series [7, 15, 16],
      regardless of the position of the wrist, whether or not the thumb was
      immobilized. Evidence of ligamentous injury in our series led us to conclude that
      scaphoid nonunion is consistently associated with carpal instability pattern. In
      our series 68% of nonunions associated with carpal collaps were present. We found
      no statistically significant correlation between carpal collaps and nontreated
      fractures or location of fracture site. Therefore, we concluded that carpal
      collaps was consistently present and, thus the critical factor in wrists with
      ununited scaphoid fractures.

PMID- 11337919
TI  - [The Crigler-Najjar syndrome, type I. Therapeutic dilemmas].
AB  - Crigler-Najjar syndrome type I is a rare hereditary disease that is manifested by
      high concentration of unconjugated bilirubin in serum, which may lead to
      neurologic disorders. Management consists of conservative therapy and partial
      liver transplantation and, since recently, hepatocyte transplantation. Both
      therapeutic procedures have been continually improved and are yielding better
      results. We present a girl, aged three and a half years, who has been living at
      the Neonatology Department of the University Childrens Hospital in Belgrade since
      birth due to the permanent need for phototherapy and other measures so as to keep
      her bilirubin at minimal level. We present numerous management dilemmas, having
      in mind the controversial attitudes of physicians from other world centres,
      starting from those who consider that surgery should be done before the age of
      six years to those who consider that the patient should be treated conservatively
      only. Our attempts to avoid neurological disorders developing in our little
      patient surpasses professional interest only, because this girl is an
      exceptionally lovely and smart child with IQ 128.

PMID- 11337920
TI  - [Solid and cystic-papillary tumor of the pancreas].
AB  - Solid and cystic-papillary tumour of the pancreas is a rare neoplasm. About 420
      cases seem to have been reported as yet. It appears almost exclusively in young
      women, although it may appear in males in all ages. This is a tumour of benign or
      low malignant potential with vary rare invasion of surrounding tissues and
      organs. Metastases of the tumour are rare. Local recurrence after surgical
      excision is also rare. About 50% of patients have no symptoms. The others may
      have upper abdominal pain or palpable abdominal mass. Complications such as
      rupture, bleeding or secondary infection, are rare. The average size of the
      tumour is cca 10 cm in diameter. The tumour is more frequent in the body and tail
      of the pancreas. New imaging techniques make diagnosis of the tumour very easy,
      but exact diagnosis is based on histological findings. Surgical excision is the
      treatment of choice. We report on a 23-year-old woman with a two-year history of
      upper abdominal pain and occasional fever, in whom ultrasonographic and CT scan
      examinations revealed a well defined mass of 5 cm in diameter. The mass was
      excised with limited resection of the pancreas along with removal of the spleen
      which was adherent to the mass so that it could not have been saved. Histological
      findings established a solid and cystic-papillary neoplasm of the pancreas. The
      recovery was uneventful. The patient was symptom-free, with normal clinical
      findings and laboratory results.

PMID- 11337921
TI  - [Synthesis and secretion of ovarian steroid hormones in polycystic ovary
      syndrome].

PMID- 11337922
TI  - [Hyperhomocysteinemia as a risk factor for cardiovascular diseases].

PMID- 11337923
TI  - [Chemotherapy of gastric adenocarcinoma].

PMID- 11337925
TI  - [Health care cooperatives. The role and contributions of this movement in the
      protection and improvement of the national health status from 1921 to 1949].
AB  - After the First World War in the devastated and destroyed country, besides hard
      economic problems, also many social and sanitary problems required appropriate
      solutions. Loss of a great number of physicians and other sanitary personnel
      during the war was badly reflected on health care of the population, especially
      in rural areas. In these conditions and on suggestions made by a young physician,
      dr. Gavrilo Kojitsh (Gavrilo Kojic), many health cooperatives were established.
      Funds were secured by membership fees payed by the members to the so-called
      patients' funds. These financial resources were intended for covering of expenses
      in case of illness or death of a cooperative member or a member of his family.
      Monthly payment depended on the number of family members and degree of health
      insurance. A cooperative was composed of 300-500 families. The first health
      cooperatives were established in 1921 and up to 1939 there were 87 cooperatives
      with 97 physicians and 71 pharmacists. The price of a doctor's consultation was 3
      4 times smaller than that in a private doctor's office, and prices of medications
      and drugs were reduced. In addition to curative treatment, the outpatient service
      of these cooperatives included maternal and infant care centres with visiting
      nursing service, sections for fight against infectious disease (vaccination),
      especially tuberculosis, education, rebuilding of villages, better water-supply,
      etc. In 1949 these health cooperatives were integrated into the new system of
      public health services.

PMID- 11337926
TI  - [50 years' of the Surgical Section of the Serbian Medical Society].

PMID- 11337927
TI  - [Usefulness of combination therapy of hybrid thrombolysis followed by back-up
      percutaneous transluminal coronary angioplasty in patients with acute myocardial
      infarction].
AB  - OBJECTIVES: Conventional thrombolytic therapy for acute myocardial infarction is
      effective for early reperfusion but has the disadvantage of a higher rate of
      bleeding complications. The purpose of this study is to elucidate efficacy and
      safety of a combined approach using a bolus injection of low dose of mutant
      tissue plasminogen activator (mt-PA) with heparin and aspirin to ensure definite
      antithrombin and antiplatelet efficacy, followed by back-up percutaneous
      transluminal coronary angioplasty(PTCA). METHODS: Patients with acute myocardial
      infarction aged < 80 years who were admitted to our institution within 3 hr of
      onset of symptoms were immediately treated with oral aspirin 330 mg and
      intravenous heparin 5,000 IU and were randomized to receive an intravenous bolus
      of mt-PA (monteplase) 15,000 IU/kg (thrombolytic group, n = 25) or no mt-PA
      (control group, n = 21), followed by angiography with PTCA if indicated. RESULTS:
      There were no differences between the two groups in patient characteristics, time
      from onset to hospital arrival, time to initial angiography, or infarct-related
      arteries. Significantly more patients had Thrombolysis in Myocardial Infarction
      flow grade 3 and grade 2/3 at the initial angiography in the thrombolytic group
      than in the control group (32.0% vs 4.8%, 68.0% vs 14.3%; p = 0.020, p = 0.0003,
      respectively). PTCA was performed in 88% of the thrombolytic group (stenting
      employed in 64%) and 95.5% of the control group (stenting in 57%), and the
      success rate was 95.5% and 100%, respectively. No acute or subacute coronary
      occlusion was found in either group. Bleeding complications occurred in only one
      patient in the thrombolytic group, which was bleeding associated with vomiting,
      and no difference was found in other complications between the two groups.
      Radionuclide ventriculography using quantitative gated single photon emission
      computed tomography showed left ventricular end-diastolic volume and left
      ventricular end-systolic volume tended to be smaller, and the ejection fraction
      after 3 months of treatment tended to be higher in the thrombolytic group.
      Myocardial salvage volume was significantly higher in the thrombolytic group.
      CONCLUSIONS: Hybrid thrombolysis using a low dose of mt-PA with aspirin and
      heparin promoted significantly early reperfusion. Also, successful reperfusion is
      achievable at higher rates with back-up PTCA without an increase in
      complications.

PMID- 11337928
TI  - [Pressure wire guide provisional coronary stent implantation].
AB  - OBJECTIVES: Whether coronary artery lesion successfully dilated by balloon
      angioplasty should be stented or not is unclear. The purpose of this study is to
      evaluate the provisional stent implantation method assessing residual ischemia by
      pressure wire. METHODS: Thirty-one patients with de-novo lesions suitable for
      stenting were enrolled in a pressure wire guided provisional stent study. The
      pressure wire was used to assess the fractional flow reserve(FFR) before and
      after balloon angioplasty. When the FFR after angioplasty was less than 0.75,
      stent implantation was planned. Patients with lesions consisting of an
      intermediate stenosis proximal to the target lesion, chronic total occlusion,
      bypass graft and left main lesion were excluded from the study. Stent
      implantation was permitted even if the FFR was more than 0.75 when the operator
      thought stenting was necessary. Medical treatment was given with aspirin 162
      mg/day, cilostazol 200 mg/day for 6 months and additional ticlopidine 200 mg/day
      for a month after stenting the lesion. RESULTS: Target vessel was the left
      anterior descending coronary artery in 19 lesions, the right coronary artery in
      3, and the circumflex coronary artery in 9. Stent implantation was performed in
      seven (23%) of 31 lesions and the other 24(77%) lesions were treated with only
      balloon angioplasty. The FFR before intervention was 0.58 +/- 0.16, and improved
      to 0.87 +/- 0.07 (p < 0.0001). Percentage diameter stenosis before intervention
      was 70.7 +/- 12.6% and improved to 20.1 +/- 13.3% (p < 0.0001) after
      intervention. There was no major cardiac event (death, coronary artery bypass
      grafting, myocardial infarction, stent thrombosis). Six months follow-up
      angiography was performed in 27 patients (87%). Angiographic restenosis
      (percentage diameter stenosis > or = 50%) was found in four patients (15%). A new
      lesion was found in two patients. Target vessel revascularization was performed
      in six patients (21%). CONCLUSIONS: Lesions successfully dilated by balloon
      angioplasty with FFR > or = 0.75 do not require stenting.

PMID- 11337929
TI  - [Optimal setting of focus points for myocardial contrast echocardiography with
      intravenous Optison (FS-69): an experimental study].
AB  - OBJECTIVES: Myocardial contrast echocardiography is useful to assess myocardil
      perfusion, but myocardial opacification is affected by the setup of the
      ultrasonic equipment. The optimal setting of focus points for adequate
      opacification of the myocardium was examined in myocardial contrast
      echocardiography. METHODS: Myocardial contrast echocardiography was performed in
      six dogs using triggered second harmonic technology following intravenous
      administration of Optison(FS-69). The short-axis view was recorded and baseline
      subtracted video intensity(peak intensity: PI) was calculated at three regions of
      the left ventricular wall, the anterior, septum, and posterior walls, to evaluate
      myocardial opacification. The focus point was set at near(2 cm), middle(4 cm) and
      far(6 cm)points. The myocardial opacification was evaluated at each focus
      setting. The effect of the acoustic power was also examined by changing the
      mechanical index to 1.6, 1.2 or 0.8. RESULTS: Myocardial opacification was
      recognized at all focus points, and segments near the focus points had high PI.
      However, the PI of the posterior wall was lowest at near focus, whereas the PI of
      the anterior wall was lowest at far focus. The difference of PI between the
      anterior and posterior walls was significant (p < 0.05, p < 0.01, respectively)
      at either focus point. Adequate myocardial opacification of all segments was
      observed when the focus was set at the middle point. The PI of the whole left
      ventricle increased relative to mechanical index. CONCLUSIONS: Setting up of
      focus points at the middle of the left ventricle provides more homogeneous
      myocardial opacification of the whole left ventricle in myocardial contrast
      echocardiography, and high acoustic power possibly improves myocardial
      opacification. Inadequate setting of focus points leads to inadequate estimation
      of myocardial perfusion by myocardial contrast echocardiography.

PMID- 11337930
TI  - [Usefulness of intravenous myocardial contrast echocardiography in rats].
AB  - OBJECTIVES: Few intravenous myocardial contrast echocardiography trials have
      evaluated myocardial perfusion in small animals. The feasibility of using
      intravenous myocardial contrast echocardiography to assess the ischemic area in
      rats was investigated. METHODS: Fourteen open chest Wister male rats were
      examined. Intravenous myocardial contrast echocardiography was performed by
      fundamental and intermittent mode using a high frequency (5-12 MHz) transducer
      (SONOS 5500) with injection of NC100100 (20% dilution) into the femoral vein. The
      mechanical index was set to 1.6. Baseline-subtracted video intensity (256 level)
      was measured in the anterior, posterior, septal and lateral walls of the left
      ventricle. The left anterior descending artery was ligated in 16 rats. The area
      at risk was evaluated by myocardial contrast echocardiography and compared to the
      area of defect by Evans Blue staining. RESULTS: All wall segments were clearly
      opacified (anterior 63.8 +/- 24.7, posterior 27.0 +/- 11.0, septal 44.5 +/- 11.6,
      lateral 52.3 +/- 19.1), although the baseline-subtracted video intensity of the
      posterior wall was low. The area at risk was clearly observed, and there was a
      good correlation with the nonperfused area by Evans Blue staining (y = 1.13x
      3.54, r = 0.98). CONCLUSIONS: Intravenous myocardial contrast echocardiography
      can detect the perfusion defect even in rats using a high frequency transducer
      and suitable setup of equipment.

PMID- 11337931
TI  - [Unusual changes detected by iodine-123 15-(p-iodophenyl)-3-R,S
      methylpentadecanoic acid myocardial single photon emission computed tomography in
      the process of acute myocardial infarction: a case report].
AB  - Iodine-123 15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid myocardial single
      photon emission computed tomography(iodine-123 BMIPP myocardial SPECT) is useful
      for the diagnosis and evaluation of ischemic myocardial disease or
      cardiomyopathy. Changes in fatty acid metabolism in the post-myocardial ischemic
      state were evaluated using iodine-123 BMIPP myocardial SPECT. A 77-year-old woman
      was hospitalized for treatment of acute myocardial infarction. Emergency coronary
      angiography showed severe stenosis with delayed filling of contrast medium in the
      middle portion of the left anterior descending artery, so primary percutaneous
      transluminal coronary angioplasty was performed successfully. On the second day,
      iodine-123 BMIPP uptake was decreased slightly on the early imaging in the apico
      anterior region, and increased slightly on the delayed imaging. On the seventh
      day, iodine-123 BMIPP uptake was decreased moderately or markedly in the apico
      anterior region on the early imaging, and decreased markedly on the delayed
      imaging. Iodine-123 BMIPP myocardial SPECT subsequently became almost normalized.
      These unusual dynamic changes In iodine-123 BMIPP myocardial SPECT imaging may
      reflect metabolic changes of fatty acids in the ischemic state, the size of the
      triacylglycerol pool, and the degree of turnover in the triacylglycerol pool.

PMID- 11337932
TI  - [Coronary blood flow velocity pattern after reperfusion therapy for acute
      myocardial infarction].

PMID- 11337933
TI  - Physiological significance of beta-adrenergic receptor polymorphisms: in-vivo or
      in-vitro veritas?

PMID- 11337934
TI  - Arg389Gly beta 1-adrenoceptor polymorphism varies in frequency among different
      ethnic groups but does not alter response in vivo.
AB  - There are marked interethnic differences in beta 1-adrenoceptor-mediated
      responsiveness, with sensitivity decreased in African-Americans and increased in
      Chinese compared with Caucasians. Therefore, the frequency of a common naturally
      occurring polymorphism of the human beta 1-adrenoceptor gene (Arg389Gly), which
      has functional importance in vitro, was determined in 194 African-Americans, 316
      Caucasian-Americans, 221 Hispanic-Americans and 142 Chinese. African-Americans
      were found to have a significantly lower frequency of the Arg389 allele than the
      other three ethnic groups (all P < 0.01). In the populations studied, the order
      of the distribution of the Arg389 allele was: Chinese (74%) > Caucasians (72%) >
      Hispanics (67%) > African-Americans (58%). To determine the functional
      significance of the Arg389Gly beta 1-adrenoceptor polymorphism, in-vivo heart
      rate responses to exercise were compared in healthy subjects homozygous for the
      Arg (n = 9) and Gly (n = 8) alleles. Heart rate response to exercise was not
      affected by genotype (P = 0.4). Although ethnic differences in the frequency of
      the beta 1-adrenoceptor Arg389Gly polymorphism exist, the polymorphism does not
      appear to have functional significance in healthy subjects and therefore may not
      contribute to ethnic differences in response to drugs acting through the beta 1
      adrenoceptor.

PMID- 11337935
TI  - In-vivo studies do not support a major functional role for the Gly389Arg beta 1
      adrenoceptor polymorphism in humans.
AB  - beta 1-adrenoceptors play a pivotal role in regulating contractility and heart
      rate in the human heart. Recently, a polymorphism of the beta 1-adrenoceptor has
      been detected: at amino acid position 389 either Gly or Arg has been found with
      the Gly389 exhibiting reduced responsiveness upon agonist-induced stimulation in
      vitro. In order to find out whether the Gly389 polymorphism exhibits blunted
      responsiveness also in vivo we studied, in healthy volunteers, the effects of
      exercise on heart rate and heart rate-corrected duration of electromechanical
      systole (QS2c as a measure of inotropism) which, in humans, is mediated by beta 1
      adrenoceptors stimulation. Twenty-four healthy volunteers (12 female, 12 male)
      homozygous for the Gly389 or Arg389 exercised on a bicycle in supine position
      (25, 50, 75 and 100 W for 5 min each), and heart rate and QS2c were assessed; in
      addition, plasma renin activity (PRA) was determined which is also regulated by
      beta 1-adrenoceptors in humans. Exercise caused work-load dependent increases in
      heart rate and PRA, and shortening of QS2c; however, these changes were not
      significantly different between the Gly389 and Arg389 polymorphism. Thus, these
      three beta 1-adrenoceptor responses did not differ between volunteers with the
      Arg389 versus the Gly389 polymorphism. Intragroup analysis, however, revealed
      that exercise induced increase in heart rate and shortening of QS2c were higher
      in female than in male volunteers. In conclusion, our data do not support the
      idea that the reduced responsiveness of Gly389 against agonist-induced
      stimulation observed in vitro is of major functional importance in vivo.

PMID- 11337936
TI  - Functional characterization of human N-acetyltransferase 2 (NAT2) single
      nucleotide polymorphisms.
AB  - N-Acetyltransferase 2 (NAT2) catalyses the activation and/or deactivation of a
      variety of aromatic amine drugs and carcinogens. Polymorphisms in the N
      acetyltransferase 2 (NAT2) gene have been associated with a variety of drug
      induced toxicities, as well as cancer in various tissues. Eleven single
      nucleotide polymorphisms (SNPs) have been identified in the NAT2 coding region,
      but the specific effects of each of these SNPs on expression of NAT2 protein and
      N-acetyltransferase enzymatic activity are poorly understood. To investigate the
      functional consequences of SNPs in the NAT2 coding region, reference NAT2*4 and
      NAT2 variant alleles possessing one of the 11 SNPs in the NAT2 coding region were
      cloned and expressed in yeast (Schizosaccharomyces pombe). Reductions in
      catalytic activity for the N-acetylation of a sulfonamide drug (sulfamethazine)
      and an aromatic amine carcinogen (2-aminofluorene) were observed for NAT2
      variants possessing G191A (R64Q), T341C (I114T), A434C (E145P), G590A (R197Q),
      A845C (K282T) or G857A (G286T). Reductions in expression of NAT2 immunoreactive
      protein were observed for NAT2 variants possessing T341C, A434C or G590A.
      Reductions in protein stability were noted for NAT2 variants possessing G191A,
      A845C, G857A or, to some extent, G590A. No significant differences in mRNA
      expression or transformation efficiency were observed among any of the NAT2
      alleles. These results suggest two mechanisms for slow acetylator phenotype(s)
      and more clearly define the effects of individual SNPs on human NAT2 expression,
      stability and catalytic activity.

PMID- 11337937
TI  - MDR1 pharmacogenetics: frequency of the C3435T mutation in exon 26 is
      significantly influenced by ethnicity.
AB  - P-glycoprotein (PGP), the product of the multidrug resistance gene (MDR1), acts
      as an energy-dependent efflux pump that exports its substrates out of the cell.
      PGP expression is an important factor regulating absorption of a wide variety of
      medications. It has also been associated with intrinsic and acquired cross
      resistance to a number of structurally unrelated anticancer drugs. A single
      nucleotide polymorphism (SNP) in exon 26 of the MDR1 gene, C3435T, was recently
      correlated with PGP protein levels and substrate uptake. Individuals homozygous
      for the T allele have more than four-fold lower PGP expression compared with CC
      individuals. As overexpression of PGP has been associated with altered drug
      absorption, therapy-resistant malignancies, and lower concentrations of HIV-1
      protease inhibitors, this SNP may provide a useful approach to individualize
      therapy. To facilitate clinical application throughout the world, 1280 subjects
      from 10 different ethnic groups were evaluated for this SNP using the polymerase
      chain reaction-restriction fragment length polymorphism assay and the genotype
      and allele frequency for each group were ascertained. Marked differences in
      genotype and allele frequency were apparent between the African populations and
      the Caucasian/Asian populations (P < 0.0001). The Ghanaian, Kenyan, African
      American and Sudanese populations studied had frequencies of 83%, 83%, 84% and
      73%, respectively, for the C allele. The British Caucasian, Portuguese, South
      west Asian, Chinese, Filipino and Saudi populations had lower frequencies of the
      C allele compared to the African group (48%, 43%, 34%, 53%, 59%, and 55%,
      respectively). The high frequency of the C allele in the African group implies
      overexpression of PGP and may have important therapeutic and prognostic
      implications for use of PGP dependent drugs in individuals of African origin.

PMID- 11337938
TI  - In-vitro metabolism of celecoxib, a cyclooxygenase-2 inhibitor, by allelic
      variant forms of human liver microsomal cytochrome P450 2C9: correlation with
      CYP2C9 genotype and in-vivo pharmacokinetics.
AB  - In-vitro studies were conducted to assess the impact of CYP2C9 genotype on the
      metabolism (methyl hydroxylation) and pharmacokinetics of celecoxib, a novel
      cyclooxygenase-2 inhibitor and CYP2C9 substrate. When compared to cDNA-expressed
      wild-type CYP2C9 (CYP2C9*1), the Vmax/Km ratio for celecoxib methyl hydroxylation
      was reduced by 34% and 90% in the presence of recombinant CYP2C9*2 and CYP2C9*3,
      respectively. These data indicated that the amino acid substitution at position
      359 (Ile to Leu) elicited a more pronounced effect on the metabolism of celecoxib
      than did a substitution at position 144 (Arg to Cys). The Vmax/Km ratio was also
      decreased in microsomes of livers genotyped CYP2C9*1/*2 (47% decrease, mean of
      two livers), or CYP2C9*1/*3 (59% decrease, one liver). In all cases, these
      changes were largely reflective of a decrease in Vmax, with a minimal change in
      Km. Based on simulations of the in-vitro data obtained with the recombinant
      CYP2C9 proteins, it was anticipated that the pharmacokinetics of celecoxib (as a
      much as a five-fold increase in plasma AUC) would be altered (versus CYP2C9*1/*1
      subjects) in subjects genotyped heterozygous or homozygous for the CYP2C9*2
      (Cys144) or CYP2C9*3 (Leu359) allele. In a subsequent clinical study, the AUC of
      celecoxib was increased (versus CYP2C9*1/*1 subjects) approximately 2.2-fold
      (range, 1.6-3-fold) in two CYP2C9*1/*3 subjects and one CYP2C9*3/*3 subject
      receiving a single oral dose (200 mg) of the drug. In contrast, there was no
      significant change in celecoxib AUC in two subjects genotyped CYP2C9*1/*2.

PMID- 11337939
TI  - Cellular localization and regional distribution of CYP2D6 mRNA and protein
      expression in human brain.
AB  - The cytochrome P4502D6 (CYP2D6) is involved in the biotransformation of many
      drugs which predominantly act in the central nervous system (CNS), including
      opioids, various psychotrophic drugs and neurotoxins. Until now, however, only
      controversial information is available regarding the presence of CYP2D6 in CNS.
      In this study, the regional and cellular expression of CYP2D6 transcripts and
      proteins in postmortem brain tissues of three individuals was analysed. A
      combination of in-situ hybridization coupled with immunohistochemistry on
      adjacent sections allowed simultaneous detection of CYP2D6 mRNA and protein.
      However, discrepancies existed in the results such that the mRNA was more widely
      distributed in the brain areas analysed compared to the protein. Neuronal cells,
      as well as glial cells, showed labelling for mRNA in brain regions such as the
      neocortex, caudate nucleus, putamen, globus pallidus, hippocampus, hypothalamus,
      thalamus, substantia nigra and cerebellum. In contrast, CYP2D6 protein was
      primarily localized in large principal neurons such as pyramidal cells of the
      cortex, pyramidal cells of the hippocampus, and Purkinje cells of the cerebellum.
      In glial cells, CYP2D6 protein was absent. These results provide clear evidence
      of CYP2D6 expression in certain regions of the CNS and may indicate the role
      CYP2D6 plays in a number of drug interactions that are of potential clinical
      importance for neurological diseases.

PMID- 11337941
TI  - Sensitivity of AXB/BXA recombinant inbred lines of mice to the locomotor
      activating effects of cocaine: a quantitative trait loci analysis.
AB  - The present study was conducted in order to characterize putative quantitative
      trait loci (QTL) for cocaine-induced activation in the AXB/BXA recombinant inbred
      (RI) lines of mice. Locomotor activity was measured in the AXB/BXA and progenitor
      A/J and C57BL/6J strains using a computerized open-field apparatus following
      saline or cocaine (0, 5, 10, 20 mg/kg) administration (i.p.). Analyses were
      conducted on phenotypes including both novelty (responses under initial saline
      conditions) and cocaine-induced locomotor activity. Significant differences were
      observed across RI lines on all measures. Gender differences in sensitivity to
      the activating effects of cocaine were not observed. The wide and continuous
      distributions of phenotypic responses in the AXB/BXA RI lines suggested polygenic
      regulation. Initial basal locomotor activity was significantly correlated with
      cocaine-induced activation (raw scores) (r = 0.60, P = 0.0021) but not with
      cocaine difference scores (r = 0.370, P = 0.082). Simple regression and interval
      mapping were used to initially identify significant gene markers associated with
      novelty and cocaine-induced activation. Subsequently, composite interval mapping
      was used to increase the accuracy in mapping individual loci. QTL analysis of
      cocaine-induced activation (difference scores--20 mg/kg dose) identified
      significant loci on chromosomes 12 (23 cM), and 15 (46.8 cM). The significant
      QTLs were identified on chromosomes 12 and 15 map to regions in proximity to
      genes for the somatostatin 1 (Smstr1 -23 cM) and 3 (Smstr3 -46.3 cM) receptors,
      respectively. Further research employing AcB/BcA recombinant congenic lines of
      mice will be employed to confirm the QTL on chromosomes 12 and 15 identified in
      the present study.

PMID- 11337940
TI  - Basal cell carcinomas: association of allelic variants with a high-risk subgroup
      of patients with the multiple presentation phenotype.
AB  - Previous studies have shown that patients who present at first or a later
      presentation with a cluster of new basal cell carcinoma (BCC) comprise a
      subgroup, termed multiple presentation phenotype (MPP), that is at increased risk
      of developing further lesions. In this study, we examined the hypothesis that
      patients who develop multiple clusters are a high-risk subgroup. We found, in a
      total group of 926 BCC patients, 32 patients with 2-5 BCC clusters (multiple
      cluster MPP) and 113 cases with only one cluster (single cluster MPP). Multiple
      cluster MPP cases had mean of 11.3 BCC compared with 3.7 in single cluster MPP
      cases during similar follow-up. Ultraviolet (UV) exposure in these groups was
      similar. We determined whether the multiple cluster MPP was associated with
      characteristics associated with sensitivity to UV or glutathione S-transferase
      (GST) GSTT1, GSTM1, cytochrome P450 (CYP) CYP2D6, tumour necrosis factor (TNF)
      alpha and vitamin D receptor (VDR) genotypes previously associated with BCC
      presentational phenotypes. While the frequencies of blue eyes and male gender
      were greater in multiple cluster than single cluster cases, these differences
      were not significant. In multiple cluster cases, mean age at first presentation
      with single tumours occurred earlier and the frequencies of CYP2D6 extensive
      metabolizer (EM) (94.4%) and GSTT1 null (41.2%) were significantly greater (P =
      0.028 and P = 0.004) than in single cluster cases (67.1% and 14.3%,
      respectively). The odds ratios for the individual associations of CYP2D6 EM and
      GSTT1 null with the multiple cluster MPP were relatively larger; 15.5 and 7.39,
      respectively. TNF-alpha and VDR genotypes were not associated with multiple
      cluster MPP. We propose that the MPP is not the consequence of excessive UV
      exposure but rather reflects the presence of a distinct BCC subgroup which is
      defined by combinations of risk genes.

PMID- 11337942
TI  - Genetic variants of the serotonin system and weight change during clozapine
      treatment.
AB  - Clozapine-induced weight gain may impair health and affect patient compliance.
      The aim of this study is to investigate the relationship between the genetic
      variants of the serotonin system and clozapine-induced body weight change (BWC).
      Ninety-three treatment-resistant schizophrenic patients were weighed monthly for
      4 months during clozapine treatment. At the conclusion of treatment, patients had
      gained an average of 2.4 kg body weight, with BWC ranging from -17.5 to +12.9 kg.
      The levels of the serotonin transporter variants, serotonin 2A, serotonin 2C and
      serotonin 6, demonstrated no statistically significant relationship to BWC.
      Patients with a lower initial body mass index demonstrated a greater weight gain
      associated with clozapine treatment. Further exploration of the neurotransmitters
      implicated in the antipsychotic-induced BWC is important in order to reduce the
      morbidity and noncompliance associated with weight gain.

PMID- 11337943
TI  - Genetic polymorphisms of thiopurine S-methyltransferase and 6-mercaptopurine
      toxicity in Japanese children with acute lymphoblastic leukaemia.

PMID- 11337944
TI  - Allelotype frequency of the thiopurine methyltransferase (TPMT) gene in Japanese.
AB  - Polymorphisms at three loci in the thiopurine methyltransferase (TPMT) gene are
      known to be responsible for azathioprine and 6-mercaptopurine (6MP) toxicity.
      Among them, only TPMT*3C variant allele with A719G mutation was found in 15/522
      (2.9%; 17/1044 alleles; 1.6%) Japanese individuals including two homozygotes. The
      allele frequency was different from that in Caucasians, and investigation of TPMT
      polymorphisms with consideration of ethnic differences before administration of
      azathioprine or 6MP may provide clinically useful information.

PMID- 11337945
TI  - Brandon/Hill selected list of print books and journals for the small medical
      library.
AB  - After thirty-six years of biennial updates, the authors take great pride in being
      able to publish the nineteenth version (2001) of the "Brandon/Hill Selected List
      of Print Books and Journals for the Small Medical Library." This list of 630
      books and 143 journals is intended as a selection guide for health sciences
      libraries or similar facilities. It can also function as a core collection for a
      library consortium. Books and journals are categorized by subject; the book list
      is followed by an author/editor index, and the subject list of journals, by an
      alphabetical title listing. Due to continuing requests from librarians, a
      "minimal core list" consisting of 81 titles has been pulled out from the 217
      asterisked (*) initial-purchase books and marked with daggers (dagger *) before
      the asterisks. To purchase the entire collection of 630 books and to pay for 143
      2001 journal subscriptions would require $124,000. The cost of only the
      asterisked items, books and journals, totals $55,000. The "minimal core list"
      book collection costs approximately $14,300.

PMID- 11337946
TI  - Creating a Web-accessible, point-of-care, team-based information system
      (PointTIS): the librarian as publisher.
AB  - The Internet has created new opportunities for librarians to develop information
      systems that are readily accessible at the point of care. This paper describes
      the multiyear process used to justify, fund, design, develop, promote, and
      evaluate a rehabilitation prototype of a point-of-care, team-based information
      system (PoinTIS) and train health care providers to use this prototype for their
      spinal cord injury and traumatic brain injury patient care and education
      activities. PoinTIS is a successful model for librarians in the twenty-first
      century to serve as publishers of information created or used by their parent
      organizations and to respond to the opportunities for information dissemination
      provided by recent technological advances.

PMID- 11337947
TI  - Circulation of core collection monographs in an academic medical library.
AB  - Academic medical librarians responsible for monograph acquisition face a
      challenging task. From the plethora of medical monographs published each year,
      academic medical librarians must select those most useful to their patrons.
      Unfortunately, none of the selection tools available to medical librarians are
      specifically intended to assist academic librarians with medical monograph
      selection. The few short core collection lists that are available are intended
      for use in the small hospital or internal medicine department library. As these
      are the only selection tools available, however, many academic medical librarians
      spend considerable time reviewing these collection lists and place heavy emphasis
      on the acquisition of listed books. The study reported here was initiated to
      determine whether the circulation of listed books in an academic library
      justified the emphasis placed on the acquisition of these books. Circulation
      statistics for "listed" and "nonlisted" books in the hematology (WH) section of
      Indiana University School of Medicine's Ruth Lilly Medical Library were studied.
      The average circulation figures for listed books were nearly two times as high as
      the corresponding figures for the WH books in general. These data support the
      policies of those academic medical libraries that place a high priority on
      collection of listed books.

PMID- 11337948
TI  - Assessment of Customer Service in Academic Health Care Libraries (ACSAHL): an
      instrument for measuring customer service.
AB  - OBJECTIVES: In a pilot study, the library had good results using SERVQUAL, a
      respected and often-used instrument for measuring customer satisfaction. The
      SERVQUAL instrument itself, however, received some serious and well-founded
      criticism from the respondents to our survey. The purpose of this study was to
      test the comparability of the results of SERVQUAL with a revised and shortened
      instrument modeled on SERVQUAL. The revised instrument, the Assessment of
      Customer Service in Academic Health Care Libraries (ACSAHL), was designed to
      better assess customer service in academic health care libraries. METHODS:
      Surveys were sent to clients who had used the document delivery services at three
      academic medical libraries in Texas over the previous twelve to eighteen months.
      ACSAHL surveys were sent exclusively to clients at University of Texas (UT)
      Southwestern, while the client pools at the two other institutions were randomly
      divided and provided either SERVQUAL or ACSAHL surveys. RESULTS: Results
      indicated that more respondents preferred the shorter ACSAHL instrument to the
      longer and more complex SERVQUAL instrument. Also, comparing the scores from both
      surveys indicated that ACSAHL elicited comparable results. CONCLUSIONS: ACSAHL
      appears to measure the same type of data in similar settings, but additional
      testing is recommended both to confirm the survey's results through data
      replication and to investigate whether the instrument applies to different
      service areas.

PMID- 11337949
TI  - Information needs of clinical teams: analysis of questions received by the
      Clinical Informatics Consult Service.
AB  - OBJECTIVES: To examine the types of questions received by Clinical Informatics
      Consult Service (CICS) librarians from clinicians on rounds and to analyze the
      number of clearly differentiated viewpoints provided in response. DESIGN:
      Questions were retrieved from an internal database, the CICS Knowledge Base, and
      analyzed for redundancy by subject analysis. The unique questions were classified
      into ten categories by subject. Treatment-related questions were analyzed for the
      number of viewpoints represented in the librarian's response. RESULTS: The CICS
      Knowledge Base contained 476 unique questions and 71 redundant questions. Among
      the unique queries, the top two categories accounted for 67%: treatment (36%) and
      disease description (31%). Within the treatment-related subset, 138 questions
      (59%) required representation of more than one viewpoint in the librarian's
      response. DISCUSSION: Questions generated by clinicians frequently require
      comprehensive, critical appraisal of the medical literature, a need that can be
      filled by librarians trained in such techniques. This study demonstrates that
      many questions require representation of more than one viewpoint to answer
      completely. Moreover, the redundancy rate underscores the need for resources like
      the CICS Knowledge Base. By critically analyzing the medical literature, CICS
      librarians are providing a time-saving and valuable service for clinicians and
      charting new territory for librarians.

PMID- 11337950
TI  - The Patient Informatics Consult Service (PICS): an approach for a patient
      centered service.
AB  - The Patient Informatics Consult Service (PICS) at the Eskind Biomedical Library
      at Vanderbilt University Medical Center (VUMC) provides patients with consumer
      friendly information by using an information prescription mechanism. Clinicians
      refer patients to the PICS by completing the prescription and noting the
      patient's condition and any relevant factors. In response, PICS librarians
      critically appraise and summarize consumer-friendly materials into a targeted
      information report. Copies of the report are given to both patient and clinician,
      thus facilitating doctor-patient communication and closing the clinician
      librarian feedback loop. Moreover, the prescription form also circumvents many of
      the usual barriers for patients in locating information, namely, patients'
      unfamiliarity with medical terminology and lack of knowledge of authoritative
      sources. PICS librarians capture the time and expertise put into these reports by
      creating Web-based pathfinders on prescription topics. Pathfinders contain
      librarian-created disease overviews and links to authoritative resources and seek
      to minimize the consumer's exposure to unreliable information. Pathfinders also
      adhere to strict guidelines that act as a model for locating, appraising, and
      summarizing information for consumers. These mechanisms--the information
      prescription, research reports, and pathfinders--serve as steps toward the long
      term goal of full integration of consumer health information into patient care at
      VUMC.

PMID- 11337951
TI  - Changes in learning-resource use across physicians' learning episodes.
AB  - INTRODUCTION: This study explores the numbers of learning resources physicians
      use at each stage in self-directed learning episodes addressing general problems.
      MATERIALS AND METHODS: A survey of a statewide random sample of doctors estimated
      the number of resources used at each stage in solving various general problems.
      RESULTS: The 50% response rate for faculty allowed generalization of findings to
      the population of these physicians; the rate for nonfaculty physicians was too
      low to allow generalization. Faculty findings showed (1) broader resource use in
      learning about diseases than diagnosis or therapeutics (2) comparable numbers of
      resources used in deciding whether to take on the learning problem and learning
      the required skills and knowledge, (3) greater numbers of resources selected to
      evaluate the problem and to learn the required skills and knowledge than to gain
      experience with the newly learned skills and knowledge, and (4) support for
      assertions that doctors value learning resources that are accessible, applicable,
      familiar, and time effective. DISCUSSION: The findings were interpreted in light
      of theory describing physicians' self-directed learning episodes, and
      implications are presented for physicians-in-training, physicians, and medical
      librarians.

PMID- 11337952
TI  - Designing a library: everyone on the same page?
AB  - Excerpts are presented from an interview by the Bulletin of the Medical Library
      Association buildings projects editor with four academic health sciences library
      directors: one who had recently completed a major library building project and
      three who were involved in various stages of new building projects. They share
      their experiences planning for and implementing library-building programs. The
      interview explores driving forces leading to new library buildings, identifies
      who should be involved, recalls the most difficult and exciting moments of the
      building projects, relates what they wished they had known before starting the
      project, assesses the impact of new library facilities on clients and services,
      reviews what they would change, and describes forces impacting libraries today
      and attributes of the twenty-first century library.

PMID- 11337953
TI  - Building a retrospective collection in pharmacy: a brief history of the
      literature with some considerations for U.S. health sciences library
      professionals.
AB  - This paper argues that historical works in pharmacy are important tools for the
      clinician as well as the historian. With this as its operative premise,
      delineating the tripartite aspects of pharmacy as a business enterprise, a
      science, and a profession provides a conceptual framework for primary and
      secondary resource collecting. A brief history and guide to those materials most
      essential to a historical collection in pharmacy follows. Issues such as
      availability and cost are discussed and summarized in checklist form. In
      addition, a glossary of important terms is provided as well as a list of all the
      major U.S. dispensatories and their various editions. This paper is intended to
      serve as a resource for those interested in collecting historical materials in
      pharmacy and pharmaco-therapeutics as well as provide a history that gives
      context to these classics in the field. This should provide a rationale for
      selective retrospective collection development in pharmacy.

PMID- 11337954
TI  - Database-generated Web pages: the Norris Medical Library experience.

PMID- 11337955
TI  - One, two, three....

PMID- 11337956
TI  - SUNY Biomedical Communication Network: Irwin Pizer.

PMID- 11337957
TI  - Nutrient digestibility and intestinal viscosities in broiler chickens fed on
      wheat diets, as compared to maize diets with added guar gum.
AB  - 1. Three maize diets containing 0, 1 or 3 g of guar gum per kg and 2 wheat diets
      were given to male broiler chickens for measurements of growth performance and
      nutrient digestibility. 2. The intestinal viscosities found with wheat diets were
      within the range of those observed with the 3 maize diets. The correlations
      between in vivo and in vitro viscosities were higher with real than with
      potential applied viscosity. 3. The gain:food ratio decreased (P < 0.05) with the
      addition of 3 g guar gum/kg. The mean gain:food ratio observed for wheat diets
      was lower (P = 0.007) than the mean value found for the 3 maize diets. 4. The
      negative effects of increased intestinal viscosity due to guar gum addition on
      nutrient digestibility were highest for lipids and lowest for starch. 5. Wheat
      diets resulted in much lower (P < 0.001) starch apparent digestibility compared
      to maize diets with added guar gum despite similar mean intestinal viscosities in
      the 2 groups of diets. Apparent lipid digestibility with wheat diets was lower (P
      < 0.01) than the value predicted from intestinal viscosity, the predictive model
      having been calculated with the guar gum added maize diets. Apparent protein
      digestibility did not differ between wheat diets and guar gum added maize diets.
      6. It was concluded that the low apparent digestibilities of starch and lipid
      observed with wheats could not be attributed only to intestinal viscosity and
      that other factors appear to be implicated in the low digestibilities observed
      with the wheat samples tested in the present experiment.

PMID- 11337958
TI  - Assay of sperm quality in the domestic fowl by MTT reduction.
AB  - 1. An assay which measures the capacity of spermatozoa from the domestic fowl to
      reduce the colourless tetrazolium dye MTT to its highly coloured purple formazan
      pigment has been developed and characterised. 2. The assay has several advantages
      over a previous tetrazolium-based sperm quality assay: it functions without the
      unstable phenazine methosulphate and toxic cyanide reagents and, following the
      reductive reaction, the sperm suspension is solubilised to produce optically
      clear solutions without centrifugation. 3. For samples of semen from individual
      males, MTT-reduction is strongly correlated with INT-reduction, which has been
      previously shown to be a useful predictor of sperm fertilising ability.

PMID- 11337959
TI  - Application of an MTT reduction assay for assessing sperm quality and predicting
      fertilising ability of domestic fowl semen.
AB  - 1. The ability of domestic fowl spermatozoa to reduce MTT tetrazolium to its
      coloured formazan was compared with other tests of sperm quality and fertilising
      ability. 2. MTT reduction was highly correlated with sperm ATP content (r2 =
      0.85); sperm mobility (r2 = 0.62.); sperm:perivitelline layer interaction (r2 =
      0.80) and fertilizing ability (r2 = 0.83). 3. The simple, robust, MTT-reduction
      assay may therefore be used to select male chickens on the basis of their sperm
      quality and thus potential fertilising ability.

PMID- 11337960
TI  - Characterisation of hepatic microsomal glucose-6-phosphatase from broiler
      chickens.
AB  - 1. The hepatic glucose-6-phosphatase (G-6-Pase) kinetic variables from chickens
      were studied in intact and disrupted microsomes using two substrates: glucose-6
      phosphate (G-6-P) and pyrophosphate (PPi). They were studied from embryonic life
      to 51 d of age. 2. The phosphohydrolase activity studied in the broiler chicken
      liver microsomes corresponds to a true glucose-6-phosphatase. 3. The enzyme VMAX
      with both substrates in intact and disrupted microsomes showed 2 maxima: one in
      19-d-old embryos and the other in 9-d-old chickens. Pyrophosphatase (PPase) VMAX
      in intact microsomes was higher than that of the G-6-Pase at all ages studied,
      except in 12 d embryos and 3-d-old chicks. In disrupted microsomes the VMAX of
      both enzymatic activities were similar. The G-6-Pase latency was high in the 19-d
      old embryos and 51-d-old chickens. 4. The KM for PPi and G-6-Pase decreased when
      microsomes were disrupted. In intact microsomes the G-6-P KM was low in embryos
      and 3-d-old chicks and later increased. On the other hand, the PPi KM in intact
      microsomes showed little change during the animal's life and was lower than that
      of G-6-P. In disrupted microsomes the KM for both substrates were similar. 5.
      These results suggest a sequential incorporation of the G-6-Pase system
      components in the endoplasmic reticulum.

PMID- 11337961
TI  - The effects of dietary flax oil and antioxidants on ascites and pulmonary
      hypertension in broilers using a low temperature model.
AB  - 1. Three experiments were conducted using a low temperature model to induce
      pulmonary hypertension (PH) and ascites in broiler chickens. Diets containing 25
      g or 50 g flax oil/kg food and control diets with an equivalent amount of
      animal/vegetable (A/V) blend oil, with and without supplemental antioxidants
      (vitamin C and vitamin E) were used. The amount of PH was assessed by the ratio
      of right ventricle weight to total ventricle weight (RV/TV ratio). Birds were
      considered to suffer from pulmonary hypertension syndrome (PHS) if the RV/TV
      ratio was greater than 0.299. 2. In experiment 1, the test diets contained 50 g
      oil/kg food and were given during the grower period only. Birds fed on the flax
      oil diet tended to have a lower incidence of PHS, ascites and lower RV/TV ratios
      than birds fed on the control diet. However, when the flax oil diet was
      supplemented with antioxidants, the incidence of ascites, PHS, haematocrit and
      whole blood and plasma viscosity increased compared with birds fed on the flax
      oil diet without antioxidants. These effects were not seen in experiment 2, when
      the test diets containing 30 g oil/kg food (25 g flax oil plus 5 g A/V blend
      oil/kg food compared to 30 g A/V blend oil/kg food) were given during the grower
      period. However, in experiment 3, when the test diets containing 30 g oil/kg food
      were given from day 1 to week 8, birds fed on the control diet supplemented with
      antioxidants had a higher incidence of PHS than those fed on the control diet
      alone. 3. In all 3 experiments, there was no significant effect of dietary fat
      source or supplemental antioxidants on total food intake or food conversion. 4.
      We conclude that diets containing 50 g flax oil/kg food tend to reduce the
      incidence of PHS and ascites in broilers using a low temperature model but the
      results were not statistically significant. In some cases, supplementing diets
      with a combination of vitamin E and vitamin C increased the incidence of ascites
      and PHS.

PMID- 11337962
TI  - Effects of caecal ligation and colostomy on water intake and excretion in
      chickens.
AB  - 1. The effect of caecal ligation and colostomy on water intake and excretion were
      examined in chickens fed a low-protein diet or a low-protein diet supplemented
      with urea. 2. When fed a low-protein diet, the water intake and the ratio of
      water intake to food intake were increased by colostomy (P < 0.05) but not
      changed further by caecal ligation of colostomised chickens. 3. When fed a low
      protein diet supplemented with urea, the amount of water intake and the ratio of
      water intake to food intake were not changed by either treatment. 4. Total water
      excretion was much higher in the colostomised plus caeca-ligated chickens than in
      other 3 groups fed both types of diet (P < 0.05). 5. The amount of faecal water
      excretion was increased by cecal ligation in colostomised chickens fed either
      diet (P < 0.01). 6. No effect of any treatment on water balance was observed in
      chickens fed either diet. 7. It is concluded that the lower intestine plays a
      useful role in the water economy of chickens fed a low-protein diet or a low
      protein diet supplemented with urea.

PMID- 11337963
TI  - Sexing chick embryos: a rapid and simple protocol.
AB  - 1. Analysis of gene expression in the developing chick gonads requires the
      collection of male and female tissues from embryos between 3.5 d and 8.5 d of
      development. However, male and female chick embryos are indistinguishable by
      morphological examination before d 7.5 of development. 2. Sex identification of
      earlier embryos is only possible by molecular methods, which at present are
      laborious and time consuming. 3. We have devised a PCR-based sexing protocol
      which combines both sex specific and control reactions in a single tube assay.
      The assay is rapid and effective over a wide range of DNA concentrations and is
      tolerant of poor quality DNA. 4. Procedures are described for identifying the sex
      of individual embryos using either tissue samples or a small number of cells
      recovered from amniotic fluid.

PMID- 11337964
TI  - Ultraviolet light and mating behaviour in domestic broiler breeders.
AB  - 1. The perception of UVA light (320 < lambda < 400 nm) by domestic fowl may be an
      adaptation to naturally lit habitats and may still be functional in farmed
      varieties, although not utilised owing to the absence of these wavelengths in
      commercial house lighting. One function may be the mediation of sexually related
      signalling or communication. 2. In experiment 1, two groups of 41 adult broiler
      breeders (four cockerels, 37 hens) were kept under conventional fluorescent
      light, with or without fluorescent UVA supplementation amounting to 16.9% of the
      total spectral power output of the luminaires. Each light environment was
      approximately iso-illuminant as perceived by the birds. The two groups were
      exposed to the light environments alternately for five 2-day periods in a cross
      over design. Mating behaviour, production measures and time budgets were recorded
      on the second day of each period. 3. A UVA-enriched environment increased the
      number of attempted matings (1.27 vs 0.99 matings/cockerel.h) and locomotion (5.3
      vs 3.7 min/bird.hour). 4. In a second experiment, 10 hens were allowed to choose
      between four cockerels lit under different power levels of UVA (1.6%, 14.6%,
      43.5%, 57.5% of the total spectral power output of the luminaires) in a four
      armed maze. Again, each light environment was approximately iso-illuminant as
      perceived by the birds. Each hen was allowed to make one choice per day over four
      days, with the position of the cockerels and the UVA levels interchanged each
      day. This schedule was repeated with the same hens for two other groups of four
      cockerels. 5. At a distance of no less than 60 cm from the cockerel, the hens
      spent most time inspecting whichever cockerel was lit by 1.6% or 14.6% UVA (1.33
      vs 1.37 vs 1.22 vs 1.16 log seconds/hen.choice, respectively for increasing UVA
      level). Similarly, when allowed to approach closer to the cockerels, the hens
      spent most time in the arm which contained a cockerel lit by 14.6% UVA light,
      (1.62 vs 1.88 vs 1.69 vs 1.51 log s/hen.choice, respectively for increasing UVA
      level). 6. UVA is clearly implicated in the transmission of sexual signals or
      communication which may have implications for the welfare and production of
      broiler breeders.

PMID- 11337965
TI  - Development of pecking damage in layer pullets in relation to dietary protein
      source.
AB  - 1. In recent years, the UK egg industry has become increasingly dependent on
      plant protein sources, in particular soyabean meal, and it has been suggested
      that this trend (and/or the concomitant absence of animal protein in layer diets)
      might be causally related to increased feather pecking and cannibalism. 2. This
      study examined the development of pecking damage in relation to dietary protein
      source, by rearing 12 groups of 12 layer pullets to 24 weeks of age on diets
      based on 'animal' (fishmeal) or 'plant' (soyabean meal) protein. 3. Damaging
      pecking began at 6 weeks of age, in three groups (one plant and two animal).
      Injurious pecking began at 18 weeks of age, and affected four groups (two plant
      and two animal). 4. Greater numbers of vigorous pecks/pulls were observed in
      plant protein groups throughout the experiment, although they were significantly
      higher only between 13 to 16 weeks of age. Pecking damage scores did not differ
      between treatments. 5. Dietary protein source did not affect plasma oestradiol,
      progesterone or egg production. 6. These results do not support the notion that
      inclusion of fishmeal in laying hen diets prevents or alleviates feather pecking
      and cannibalism.

PMID- 11337966
TI  - Does occasional movement make pecking devices more attractive to domestic chicks?
AB  - 1. Previous studies have shown that a bunch of string is a particularly
      attractive pecking stimulus for chicks and adult laying hens. Because movement is
      thought to be an important attribute of enrichment objects, this study determined
      whether occasional movement would affect the attractiveness of this device. 2. In
      experiment 1 the responses of pair-housed chicks to string were compared when
      devices in adjacent cages were either linked (so that pecking or pulling at the
      string in one cage moved the adjoining one) or not (separate). In experiment 2
      the devices in half the cages were jigged remotely by the experimenter whereas
      the others remained static. In both cases, the string devices were introduced
      into the cages for 10 min on each of 5 consecutive days. 3. No treatment effects
      were apparent in experiment 1 when pooled data was analysed but comparison of
      responses on days 1 and 5 revealed that only the chicks presented with non-linked
      devices showed increased interest with repeated exposure. 4. Chicks given static
      devices in experiment 2 pecked sooner, more often and longer at them than did
      those exposed to similar ones that were jigged regularly by the experimenter.
      Jigged devices attracted slightly more pecking with repeated exposure, which may
      have reflected familiarity-induced fear-reduction, but chick responses showed no
      apparent changes from day 2 onwards. Conversely, rather than showing habituation,
      the chicks pecked progressively more at the static devices with repeated
      presentation. 5. The present results show that chicks pecked readily at bunches
      of white string, thus confirming its attractive properties but that static
      devices were more attractive than those incorporating occasional movement. These
      and previous findings are discussed in terms of their implications for the
      development of effective environmental enrichment.

PMID- 11337967
TI  - Gordon Memorial Lecture. Newcastle disease.
AB  - 1. In this paper several historical and contemporary aspects of Newcastle disease
      (ND) are reviewed, with particular reference to the greater understanding which
      modern techniques have allowed. 2. Virulent ND viruses were generally thought to
      have emerged in 1926 as a result of transfer from a wild bird host reservoir but
      there is evidence that the virulent virus may have existed in poultry before
      1926. Recent findings suggest that the virulent virus may emerge in poultry as a
      result of mutations in viruses of low virulence. 3. The history of ND in Great
      Britain reflects the four known panzootics that have occurred and serves as a
      model for the impact this disease may have on poultry populations. 4. Attempts to
      control and eradicate ND are not as straightforward as it may appear; in
      particular vaccination, while preventing deaths and disease, on challenge may not
      prevent virus replication and could therefore lead to the virulent virus becoming
      endemic. 5. Village chickens are extremely important assets in most developing
      countries, representing a significant source of protein in the form of eggs and
      meat but endemic ND can cause mortality of up to 60% in village chickens.

PMID- 11337968
TI  - Effect of electrical stun/kill method, interval between killing and neck cutting
      and blood vessels cut on blood loss and meat quality in broilers.
AB  - 1. Broiler chickens were killed using either an electrical waterbath (WB system)
      delivering 120 mA per bird (50 Hz, alternating current, AC) for 4 s or an
      alternative stun/kill method (ASK system); where head-only stunning for 1 s was
      immediately followed by head-to-body (vent) application for 1 s (150 mA, 50 Hz
      sine wave AC). Within each stun/kill system, the neck was cut ventrally or
      unilaterally 20, 60, or 180 s after killing. In addition, a control group of
      broilers was stunned with 100 mA per bird in a waterbath using 1500 Hz AC for 4 s
      and were bled by a ventral neck cut within 20 s. 2. Blood leaving the neck cut
      was collected for 90 s in a bin placed on an electronic balance and blood loss
      (g/kg body weight) calculated. 3. Individually identified, unplucked and
      uneviscerated carcases were held at ambient temperature until the end of the
      experimental day and then stored overnight in an air chiller (5 degrees C). The
      carcases were dissected and the incidence of broken furculum and coracoid bones,
      haemorrhaging in P. minor and P. major muscles, and discolouration of P. major
      muscles were determined. 4. When neck cutting was performed in broilers 20 s
      after the stun or kill, the ASK and WB systems, in comparison with high frequency
      stunning, produced on average about 10 g per kg less bleed out. Within the
      stun/kill systems, broilers killed by ASK had a greater bleed out than in the WB
      system. Neck cutting at 20 s or 60 s post-kill resulted in a greater bleed out
      than when performed after a delay of 180 s. Ventral or unilateral neck cutting
      resulted in a similar bleed out. 5. Stunning broilers with 1500 Hz AC resulted in
      lower incidences of broken bones, haemorrhaging in breast muscles and muscle
      discolouration post mortem than the stun/kill systems. These defects were
      significantly lower in the ASK than in the WB system. Delayed neck cutting
      increased the severity of discolouration occurring Post mortem in the breast
      muscles. 6. It is suggested that broilers killed by ASK can be neck cut with a
      delay of up to 180 s without compromising bleed out. The incidence of broken
      bones and haemorrhaging in breast muscles are significantly less with ASK than
      WB. 7. Owing to the commercial benefits and potential for improved welfare at
      slaughter, ASK would appear to be a better method than WB.

PMID- 11337969
TI  - Metabolisable energy value and digestibility of fat and fatty acids in linseed
      determined with growing broiler chickens.
AB  - 1. In the first experiment, the AMEN of linseed was evaluated at rates of 40, 80,
      160 and 240 g/kg in a basal diet with broiler chickens aged 28 d using the total
      collection method. 2. Increasing the concentration of linseed decreased the AMEN
      of diet, from 11.78 to 8.75 MJ/kg DM, and AMEN of linseed, from 16.64 to -2.96
      MJ/kg DM. The negative values clearly indicated that linseed interacted with the
      other dietary ingredients and impaired their energy utilisation. 3. In the second
      experiment, a semipurified diet with graded addition of linseed (80, 120, 160 and
      240 g/kg DM) was evaluated for crude fat and fatty acid apparent digestibilities.
      The coefficients decreased from 0.602 to 0.359 for crude fat and from 0.661 to
      0.352 for individual fatty acids as the level of linseed increased. 4. In both
      experiments, a quadratic regression model explained the relationship between data
      better than the linear model. 5. The presence of mucilage and other
      antinutritional factors in linseed might explain the results obtained in this
      study.

PMID- 11337970
TI  - Importance of amino-acid and electrolyte balance in experimental diets used to
      determine the apparent metabolisable energy (AME) value of wheat.
AB  - 1. An experiment was done with male, Ross broiler chicks to study the effect of
      diet composition and electrolyte balance on the measurement of diet AME and
      performance parameters in diets containing high levels of wheat inclusion. 2. The
      control diet (G) was based on wheat (667 g/kg) with full-fat soya, soyabean meal,
      Extrupro and herring meal providing the protein supplements. The experimental
      treatments were based on 2 diets, one based on wheat (790 g/kg) with casein as
      the protein supplement and the other containing 667 g/kg wheat plus casein,
      cellulose and starch. Each of these was formulated to contain one of three
      concentrations of sodium and potassium bicarbonate giving final values for
      dietary electrolyte balance of approximately 90, 180 and 280 meq/kg diet. 3. DM
      intake was numerically lower with the lower level of wheat inclusion and LWG (P <
      0.05) and gain:food (P < 0.001) were reduced. ME:GE was similar for the two
      levels of wheat/casein but higher (P < 0.001) than for the control diet. 4. The
      two higher electrolyte balances improved DM intake (P < 0.01), LWG and gain:food
      (P < 0.01) compared with the diets containing no added bicarbonate. ME:GE was
      unaffected by electrolyte inclusion. 5. Viscosity of ileal digesta supernatant
      fell (P < 0.01) with increasing bicarbonate inclusion but the value for the
      highest electrolyte level was still higher than for the control diet. 6. It is
      concluded that addition of both arginine and electrolyte is needed with a
      wheat/casein diet to improve performance to levels seen with a more commercial
      diet but that the determination of diet AME, with the type of fat addition used
      in this study, is unaffected by electrolyte balance. The interaction between
      electrolyte balance and in vivo viscosity requires further study.

PMID- 11337971
TI  - Analysis of variability in nutrient digestibilities in broiler chickens.
AB  - 1. Forty commercial broiler chickens from two different breeding origins were
      used for individual measurements of growth performance from d 7 to d 21. From d
      21 to d 24 a balance experiment was carried out for the measurement of
      metabolisable energy (ME), digestibilities of lipids, starch and amino acids,
      viscosity of excreta water-extract, and amount of water loss. After this, the
      weight and length of the different parts of the gastrointestinal tract were
      measured for each bird. During the experiment, the birds were fed with an
      experimental diet containing 5 g/kg of guar gum in order to increase the
      variability of responses. 2. There were no significant (P < 0.05) differences
      between the two breeds in 21 d live weight, food:gain ratio, ME value or the
      digestibilities of lipids, starch and total amino acids. Significant (P < 0.05)
      differences between the two breeds were observed for caecal size, excreta guar
      gum degradation measured using viscosity measurements, and vent score. 3. Pooling
      all the individual data, individual ME values were correlated (r2 = 0.33) with
      individual food:gain ratios, which shows that a great part of ME variation was
      associated with individual variation. 4. Several significant (P < 0.05)
      correlations were observed between individual digestibilities and individual
      anatomical characteristics of the gastrointestinal tract. The most significant
      were concerned with the duodenum weight:length ratio correlated with ME (r =
      0.474) and the caeca weight:body weight ratio correlated with guar gum
      degradation (r = 0.495). Covariance analyses were carried out when correlations
      were significant and did not show significant interactions with the breeding
      origin of chickens.

PMID- 11337972
TI  - The effects of withdrawal of vitamin and trace mineral supplements from layer
      diets on egg yield and trace mineral composition.
AB  - 1. This study was conducted as three trials. 2. In the first trial, zinc,
      manganese, copper and iron concentrations were determined in dietary raw
      materials collected from various regions of Turkey. 3. In the second trial, 200
      Hisex Brown laying hens, 30 weeks of age, were divided into two groups. The first
      group served as controls and were fed on a standard commercial layer diet. The
      second group were fed on a commercial layer diet that was not supplemented with
      trace minerals and vitamins. Egg production, egg weight, specific gravity, food
      consumption and food efficiency of the birds in each group were determined. In
      the unsupplemented group, egg production (0.75 vs 0.83) and food intake (114 vs
      122 g) were lower than the those of the control group (P < 0.05). Food efficiency
      was 2.42 (kg food/kg gain) in the group consuming the unsupplemented diet and
      2.36 in the controls. 4. In the third trial, as in Trial 2, Hisex Brown laying
      hens, 62 weeks of age were used. In the unsupplemented group, the mean egg weight
      was significantly lower than that of controls (68.0 vs 69.6 g) (P < 0.01). 5. At
      the end of the second and third trials, egg samples collected from experimental
      groups were hard boiled in water. The levels of zinc, manganese, copper and iron
      in the egg yolk were determined. The zinc level of the egg yolk from the control
      group of second trial was higher (23.5 mg/kg) than those of the unsupplemented
      group (13.6 mg/kg).

PMID- 11337973
TI  - Dietary phosphorus supply, egg-shell deposition and plasma inorganic phosphorus
      in laying hens.
AB  - 1. In 2 experiments the effects of dietary phosphorus on relationships between
      plasma inorganic phosphorus concentration (Pi), shell and egg production and
      depletion states were measured in brown laying hens. 2. In a 12-week experiment
      dietary phosphorus concentrations from conventionally deficient (1.6 g non
      phytate-phosphorus (PNP)/kg) to moderate excess (3.9 g PNP/kg) had little effect
      on egg and shell production, although there was evidence that plasma Pi
      concentration, when not influenced strongly by shell formation, reflected dietary
      phosphorus content. 3. Among birds at each dietary phosphorus concentration there
      was a negative linear relationship between shell weight of early eggs in the
      sequence and plasma Pi concentration. The relationship was apparently not
      affected by dietary phosphorus concentration. 4. Continued feeding of the
      deficient diet to 61 weeks of age did not have effects on body weight, egg and
      shell production, other than those associated with age, but plasma Pi and bone
      measurements indicated marginal phosphorus depletion. 5. In another experiment
      excessive dietary phosphorus (11.9 g PNP/kg) fed in a cross-over design caused
      small adverse effects on shell production, increased food intake and body weight
      and increased plasma Pi content, while there was no relationship between shell
      weight and plasma Pi concentration. 6. The results are consistent with an
      indirect effect of plasma phosphorus accumulation on shell formation, probably
      via an inhibitory effect on skeletal calcium release, in addition to any effect
      of excess dietary phosphorus on intestinal calcium availability. 7. Phosphorus
      requirement and status in the laying hen are complicated by the failure to
      recognise the contribution of digestible phytate-phosphorus to the available
      phosphorus supply.

PMID- 11337974
TI  - The effect of supplementary dietary L-carnitine on the growth performance, serum
      components, carcase traits and enzyme activities in relation to fatty acid beta
      oxidation of broiler chickens.
AB  - 1. This study investigated the effects of supplementary dietary L-carnitine on
      the performance, serum components, carcase traits and specific activities of
      hepatic enzymes related to beta-oxidation of fatty acids in broiler chickens. One
      hundred and eighty 1-d-old broilers were divided into 2 groups, each with 3
      replicates, and given diets supplemented with 0 and 160 mg L-carnitine/kg for 6
      weeks. 2. Experimental results indicated that supplementary carnitine did not
      significantly influence the performance and carcase characteristics of the
      broilers. 3. The serum triacylglycerol (TG) and nonesterified fatty acid (NEFA)
      concentrations in the carnitine supplemented group were significantly lower than
      that in the control group (P < 0.05). However, the effect on serum cholesterol,
      phospholipids concentrations and lipoprotein profiles were not significant (P >
      0.05). 4. Carnitine palmitoyl transferase activity in the carnitine-supplemented
      group was significantly (P < 0.05) higher than in the control; however, carnitine
      supplementation did not significantly affect the activities of other fatty acid
      beta-oxidation enzymes. 5. The results in this study demonstrated that
      supplementary carnitine facilitated fatty acid transportation and did not
      influence the performance or carcase characteristics of broilers.

PMID- 11337975
TI  - Stability of dietary ascorbic acid and the effect of supplementation on
      reproductive performance of broiler breeder chickens.
AB  - 1. The purpose of the study was to determine the stability of dietary ascorbic
      acid and the reproductive responses of broiler breeder chickens to supplemental
      75 mg ascorbic acid/kg diet. 2. Six breeder flocks of 13,000 birds each were
      studied. Egg production, eggshell porosity, fertility, hatchability and plasma
      ascorbic acid were measured. 3. Storage of the diets under dry heat resulted in a
      linear decrease in ascorbic acid content and the rate of decline was 5-fold
      higher in the supplemented diet. 4. Differences were not detected between
      treatments in egg production, egg weight, eggshell porosity, fertility,
      hatchability or plasma ascorbic acid. 5. The results did not provide evidence of
      a beneficial reproductive response to the inclusion of ascorbic acid in
      commercial broiler breeder diets.

PMID- 11337976
TI  - The effect of conjugated linoleic acid on platelet function, platelet fatty acid
      composition, and blood coagulation in humans.
AB  - Despite extensive research on conjugated linoleic acid (CLA) showing multiple
      beneficial effects in animal models, little is known about the role of dietary
      CLA in human health. To investigate if the beneficial effects of CLA seen in
      animal models are relevant to humans, we conducted a study with 17 healthy female
      volunteers who lived in the Metabolic Research Unit of the Western Human
      Nutrition Research Center for 93 d. This paper reports only the results from this
      study that are related to the effects of CLA supplementation on blood
      coagulation, platelet function, and platelet fatty acid composition. Throughout
      the study, the subjects were fed a low-fat diet (30 en% fat, 19 en% protein, and
      51 en% carbohydrate) consisting of natural foods with the recommended dietary
      allowances for all known nutrients. After a 30-d stabilization period, subjects
      were randomly assigned to either an intervention group (n = 10) whose diet was
      supplemented with 3.9 g/d of CLA or a control group (n = 7) who received an
      equivalent amount of sunflower oil consisting of 72.6% linoleic acid with no
      detectable CLA. Platelet aggregation was measured in platelet-rich plasma using
      adenosine diphosphate, collagen, and arachidonic acid agonists. No statistical
      difference was detected between the amount of agonist required to produce 50%
      aggregation of platelet-rich plasma before and after the subjects consumed the
      CLA, with the exception of a decrease in response to collagen. This decrease was
      found in both control and intervention groups with no significant difference
      between the groups, suggesting that both linoleic acid (sunflower oil) and CLA
      might have similar effects on platelet function. The prothrombin time, activated
      partial thromboplastin time, and the antithrombin III levels in the subjects were
      determined. Again, there was no statistically significant difference in these
      three parameters when pre- and post-CLA consumption values were compared. The in
      vivo bleeding times were also unaffected by CLA supplementation (10.4 + 2.8 min
      pre- and 10.2 + 1.6 min postconsumption). Platelet fatty acid composition was not
      markedly influenced by the consumption of dietary CLA, although there was a small
      increase in the amount of the 9 cis,11 trans-18:2 isomer normally present in
      platelets after feeding CLA for 63 days. In addition, small amounts of the 8
      trans,10 cis-18:2 and the 10 trans,12 cis-18:2 isomers were detected in the
      platelets along with traces of some of the other isomers. Thus, when compared to
      sunflower oil, the blood-clotting parameters and in vitro platelet aggregation
      showed that adding 3.9 g/d of dietary CLA to a typical Western diet for 63 d
      produces no observable physiological change in blood coagulation and platelet
      function in healthy adult females. Short-term consumption of CLA does not seem to
      exhibit antithrombotic properties in humans.

PMID- 11337977
TI  - The effect of conjugated linoleic acid on plasma lipoproteins and tissue fatty
      acid composition in humans.
AB  - Conjugated linoleic acid (CLA) has been suggested by some animal studies to
      possess antiatherogenic properties. To determine, in humans, the effect of
      dietary CLA on blood lipids, lipoproteins, and tissue fatty acid composition, we
      conducted a 93-d study with 17 healthy female volunteers at the Metabolic
      Research Unit of the Western Human Nutrition Research Center. Throughout the
      study, subjects were fed a low-fat diet [30 energy percent (en%) fat, 19 en%
      protein, and 51 en% carbohydrate] that consisted of natural foods with the
      recommended dietary allowances for all known nutrients. After a 30-d
      stabilization period, subjects were randomly assigned to either an intervention
      group (n = 10) supplemented daily with capsules containing 3.9 g of CLA or a
      control group (n = 7) that received an equivalent amount of sunflower oil. The
      CLA capsules (CLA 65%) contained four major cis/trans geometric isomers (11.4% 9
      cis-,11 trans-18:2; 10.8% 8 trans-,10 cis-18:2; 15.3% 11 cis-,13 trans-18:2; and
      14.7% 10 trans-,12 cis-18:2) and their corresponding cis/cis (6.74% total) and
      trans/trans (5.99% total) varieties in smaller amounts. Fasting blood was drawn
      on study days 30 (end of the stabilization period), 60 (midpoint of the
      intervention period), and 93 (end of the intervention period). Adipose tissue
      samples were taken on days 30 and 93. CLA supplementation for 63 d did not change
      the levels of plasma cholesterol, low density lipoprotein cholesterol, high
      density lipoprotein cholesterol, and triglycerides. The weight percentage of CLA
      in plasma increased from 0.28 +/- 0.06 to 1.09 +/- 0.31 (n = 10, P < 0.05) after
      the supplementation. The 9 cis-,11 trans-isomer was the most prominent variety
      followed by the 11 cis-,13 trans- and 10 trans-,12 cis-isomers in lesser amounts.
      CLA in adipose tissue was not influenced by the supplementation (0.79 +/- 0.18 to
      0.83 +/- 0.19 wt%) (n = 10) and the 9 cis-,11 trans-variety was the only isomer
      present. Thus, contrary to findings from some animal studies, CLA does not seem
      to offer health benefits, in the short term, regarding the prevention of
      atherosclerosis in humans. CLA supplementation for 2 mon did not alter the blood
      cholesterol or lipoprotein levels of healthy, normolipidemic subjects. The
      supplementation did increase CLA in the plasma but only 4.23% of the ingested CLA
      was present in the plasma at any given time. No adverse effect of CLA
      supplementation was detected in this study.

PMID- 11337978
TI  - Peripheral differential leukocyte counts in humans vary with hyperlipidemia,
      smoking, and body mass index.
AB  - Reports of diverse relationships between blood concentrations of different lipids
      and peripheral total leukocyte count, and a unique lower peripheral monocyte
      count in hypercholesterolemia, have driven us to think that in humans, peripheral
      differential leukocyte counts may be influenced differently by different types of
      hyperlipidemia. Our subjects were Taipei residents who attended a regular health
      check program in our hospital in 1998. A total of 3,282 subjects was enrolled,
      including 1,677 normolipidemic, 960 untreated borderline hyperlipidemic, and 645
      untreated hyperlipidemic subjects. By one-way analysis of variance (ANOVA), we
      found that different types of hyperlipidemia were associated with significant
      differences in differential leukocyte counts. In hypertriglyceridemia, the total
      leukocyte count and counts of all leukocyte subtypes were significantly higher
      than those in normolipidemia. Pure hypercholesterolemia, by contrast, was
      associated with a significantly lower monocyte count and no significant
      difference in other leukocyte counts. By two-way ANOVA adjusted for presence and
      degree of hyperlipidemia, we found significantly higher counts of total
      leukocytes and of all leukocyte subtypes in smokers, and significantly positive
      trends in relationships between body mass index (BMI) and counts of all
      leukocytes, neutrophils, lymphocytes, and monocytes. By multivariate regression
      analysis including all subjects, the serum triglyceride (TG) level was positively
      correlated with total leukocyte count and counts of all subtypes except
      eosinophils. On the contrary, serum high density lipoprotein-cholesterol had a
      negative correlation with total leukocyte count and with counts of neutrophils,
      monocytes, and basophils. In these multivariate regression analyses, there was no
      significant correlation between lipid levels and eosinophil count, whereas
      smoking was consistently associated with significantly higher counts of all
      leukocyte subtypes, including eosinophils. BMI had a significantly positive
      correlation with counts of all leukocytes, neutrophils, lymphocytes, and
      monocytes.

PMID- 11337980
TI  - 1-14C-linoleic acid distribution in various tissue lipids of guinea pigs
      following an oral dose.
AB  - A recent study on the metabolism of 1-14C-alpha-linolenic acid in the guinea pig
      revealed that the fur had the highest specific activity of all tissues examined,
      48 h after dosing. The present study investigated the pattern of tissue lipid
      labeling following an oral dose of 1-14C-linoleic acid after the animals had been
      dosed for the same time as above. Guinea pigs were fed one of two diets with a
      constant linoleic acid content (18% total fatty acids) and a different content of
      alpha-linolenic acid (0.3 or 17.3%) from weaning for 3 wk and 1-14C-linoleic acid
      was given orally to each animal for 48 h prior to sacrifice. The most highly
      labeled tissues (dpm/mg of linoleic acid) were liver, followed by brain, lung and
      spleen, heart, kidney and adrenal and intestines, in both diet groups. The liver
      had almost a three-fold higher specific activity than skin and fur which was more
      extensively labeled than the adipose and carcass. Approximately two-thirds of the
      label in skin plus fur was found in the fur which, because of a low lipid mass,
      would indicate that the fur was highly labeled. All tissues derived from animals
      on the diet with the low alpha-linolenic acid level were significantly more
      labeled than the tissues from the animals on the high alpha-linolenic acid diet,
      by a factor of 1.5 to 3. The phospholipid fraction was the most highly labeled
      fraction in the liver, free fatty acids were the most labeled fraction in skin &
      fur, while triacyglycerols were the most labeled in the carcass and adipose
      tissue. In these tissues, more than 90% of the radioactivity was found in fatty
      acids with 2-double bonds in the tissue lipids. These data indicate that the
      majority of label found in guinea pig tissues 48 h after dosing was still
      associated with a fatty acid fraction with 2-double bonds, which suggests there
      was little metabolism of linoleic acid to more highly unsaturated fatty acids in
      this time frame. In this study, the labeling of guinea pig tissues with linoleic
      acid, 48 h after dosing, was quite different from the labeling with alpha
      linolenic acid reported previously. The retention of the administered
      radioactivity from 14C-linoleic acid in the whole body lipids was 1.6 times
      higher in the group fed the low alpha-linolenic acid diet (diet contained a total
      of 1.8 g PUFA/100 g diet) compared with the group fed the high alpha-linolenic
      acid diet (diet contained 3.6 g PUFA/100 g diet). The lack of retention of 14C
      labeled lipids in the whole body would be consistent with an increased rate of
      beta-oxidation of the labeled fatty acid on the diet rich in PUFA, a result
      supported by other studies using direct measurement of labeled carbon dioxide.

PMID- 11337979
TI  - Unique phospholipid metabolism in mouse heart in response to dietary
      docosahexaenoic or alpha-linolenic acids.
AB  - Diet and fatty acid metabolism interact in yet unknown ways to modulate membrane
      fatty acid composition and certain cellular functions. For example, dietary
      precursors or metabolic products of n-3 fatty acid metabolism differ in their
      ability to modify specific membrane components. In the present study, the effect
      of dietary 22:6n-3 or its metabolic precursor, 18:3n-3, on the selective
      accumulation of 22:6n-3 by heart was investigated. The mass and fatty acid
      compositions of individual phospholipids (PL) in heart and liver were quantified
      in mice fed either 22:6n-3 (from crocodile oil) or 18:3n-3 (from soybean oil) for
      13 wk. This study was conducted to determine if the selective accumulation of
      22:6n-3 in heart was due to the incorporation of 22:6n-3 into cardiolipin (CL), a
      PL most prevalent in heart and known to accumulate 22:6n-3. Although heart was
      significantly enriched with 22:6n-3 relative to liver, the accumulation of 22:6n
      3 by CL in heart could not quantitatively account for this difference. CL from
      heart did accumulate 22:6n-3, but only in mice fed preformed 22:6n-3. Diets rich
      in non-22:6n-3 fatty acids result in a fatty acid composition of
      phosphatidylcholine (PC) in heart that is unusually enriched with 22:6n-3. In
      this study, the mass of PC in heart was positively correlated with the enrichment
      of 22:6n-3 into PC. The increased mass of PC was coincident with a decrease in
      the mass of phosphatidylethanolamine, suggesting that 22:6n-3 induced PC
      synthesis by increasing phosphatidylethanolamine-N-methyltransferase activity in
      the heart.

PMID- 11337981
TI  - Effects of diets enriched in n-6 or n-3 fatty acids on cholesterol metabolism in
      older rats chronically fed a cholesterol-enriched diet.
AB  - Hypocholesterolemic effects in older animals after long-term feeding are unknown.
      Therefore, aged rats (24 wk of age) fed a conventional diet were shifted to diets
      containing 10% perilla oil [PEO; oleic acid + linoleic acid + alpha-linolenic
      acid; n-6/n-3, 0.3; polyunsaturated fatty acid/saturated fatty acid (P/S), 9.6],
      borage oil [oleic acid + linoleic acid + alpha-linolenic acid; n-6/n-3, 15.1;
      P/S, 5.3], evening primrose oil (EPO; linoleic acid + gamma-linolenic acid; P/S,
      10.5), mixed oil (MIO; oleic acid + linoleic acid + gamma-linolenic acid + alpha
      linolenic acid; n-6/n-3, 1.7; P/S, 6.7), or palm oil (PLO; palmitic acid + oleic
      acid + linoleic acid; n-6/n-3, 25.3; P/S, 0.2) with 0.5% cholesterol for 15 wk in
      this experiment. There were no significant differences in the food intake and
      body weight gain among the groups. The liver weight in the PEO (n-6/n-3, 0.3)
      group was significantly higher than those of other groups in aged rats. The serum
      total cholesterol and very low density lipoprotein (VLDL) + intermediate density
      lipoprotein (IDL) + low density lipoprotein (LDL)-cholesterol concentrations of
      the PLO (25.3) group were consistently higher than those in the other groups. The
      serum high density lipoprotein cholesterol concentrations of the PEO (0.3) and
      EPO groups were significantly lower than in the other groups at the end of the 15
      wk feeding period. The liver cholesterol concentration of the PLO (25.3) group
      was significantly higher than those of other groups. There were no significant
      differences in the hepatic LDL receptor mRNA level among the groups. Hepatic
      apolipoprotein (apo) B mRNA levels were not affected by the experimental
      conditions. The fecal neutral steroid excretion of the PLO (25.3) group tended to
      be low compared to the other groups. The results of this study demonstrate that
      both n-6 fatty acid and n-3 fatty acids such as gamma-linolenic acid and alpha
      linolenic acid inhibit the increase of serum total cholesterol and VLDL + IDL +
      LDL-cholesterol concentrations of aged rats in the presence of excess cholesterol
      in the diet compared with dietary saturated fatty acid.

PMID- 11337982
TI  - Acute effect of ethanol on 7-hydroperoxycholesterol in muscle and liver.
AB  - We tested the hypotheses that ethanol sensitivities of muscle and liver can be
      discerned in the initial periods of ethanol exposure, especially when
      acetaldehyde levels are markedly raised with cyanamide, an aldehyde dehydrogenase
      inhibitor. To test this, we measured cholesterol hydroperoxides in soleus (Type
      I) and plantaris (Type II) muscle in four groups of rats acutely (i.e., 2.5 h)
      exposed to: [S] saline (control), [Cy] cyanamide, [EtOH] ethanol, or [Cy + EtOH]
      cyanamide + ethanol. Comparative reference was also made to the response of the
      liver. After 2.5 h, ethanol alone significantly increased 7 alpha
      hydroperoxycholest-5-en-3 beta-ol (7 alpha-OOH) and 7 beta-hydroperoxycholest-5
      en-3 beta-ol (7 beta-OOH) levels in plantaris muscle. Identical qualitative
      effects were seen in rats treated with cyanamide + ethanol, but there was no
      discernible difference between groups [EtOH] and [Cy + EtOH]. In both the soleus
      muscle and liver, none of the treatments with either ethanol or cyanamide +
      ethanol had any effect on any of the measured parameters. This is the first
      report of a differential response of 7 alpha-OOH and 7 beta-OOH in Type II,
      compared to Type I predominant muscles, and the first time that muscle has been
      shown to be more sensitive than the liver in terms of its lipid marker response
      to oxidative stress. Perturbations in the muscle membrane lipid domain may
      contribute to impairment of muscle in alcoholism.

PMID- 11337983
TI  - Incorporation and distribution of saturated and unsaturated fatty acids into
      nuclear lipids of hepatic cells.
AB  - Liver nuclear incorporation of stearic (18:0), linoleic (18:2n-6), and
      arachidonic (20:4n-6) acids was studied by incubation in vitro of the [1-14C]
      fatty acids with nuclei, with or without the cytosol fraction at different times.
      The [1-14C] fatty acids were incorporated into the nuclei as free fatty acids in
      the following order: 18:0 > 20:4n-6 >> 18:2n-6, and esterified into nuclear
      lipids by an acyl-CoA pathway. All [1-14C] fatty acids were esterified mainly to
      phospholipids and triacylglycerols and in a minor proportion to diacylglycerols.
      Only [1-14C]18:2n-6-CoA was incorporated into cholesterol esters. The
      incorporation was not modified by cytosol addition. The incorporation of 20:4n-6
      into nuclear phosphatidylcholine (PC) pools was also studied by incubation of
      liver nuclei in vitro with [1-14C]20:4n-6-CoA, and nuclear labeled PC molecular
      species were determined. From the 15 PC nuclear molecular species determined,
      five were labeled with [1-14C]20:4n-6-CoA: 18:0-20:4, 16:0-20:4, 18:1-20:4, 18:2
      20:4, and 20:4-20:4. The highest specific radioactivity was found in 20:4-20:4
      PC, which is a minor species. In conclusion, liver cell nuclei possess the
      necessary enzymes to incorporate exogenous saturated and unsaturated fatty acids
      into lipids by an acyl-CoA pathway, showing specificity for each fatty acid.
      Liver cell nuclei also utilize exogenous 20:4n-6-CoA to synthesize the major
      molecular species of PC with 20:4n-6 at the sn-2 position. However, the most
      actively synthesized is 20:4-20:4 PC, which is a quantitatively minor component.
      The labeling pattern of 20:4-20:4 PC would indicate that this molecular species
      is synthesized mainly by the de novo pathway.

PMID- 11337984
TI  - Purification and characterization of an extracellular lipase from Penicillium
      candidum.
AB  - Penicillium candidum produces and secretes a single extracellular lipase with a
      monomer molecular weight of 29 kDa. However, this enzyme forms dimers and higher
      molecular weight aggregates under nondenaturing conditions. The lipase from P.
      candidum was purified 37-fold using Octyl-Sepharose CL-4B and DEAE-Sephadex
      columns. The optimal assay conditions for lipase activity were 35 degrees C and
      pH 9. The lipase was stable in the pH range of 5-6 with a pl of 5.5, but rapid
      loss of the enzyme activity was observed above 25 degrees C. Tributyrin was found
      to be the best substrate for the P. candidum lipase, among those tested. Metal
      ions such as Fe2+ and Cu2+ inhibited enzymatic activity and only Ca2+ was able to
      slightly enhance lipase activity. Ionic detergents inhibited the activity of the
      enzyme, whereas nonionic detergents stimulated lipase activity.

PMID- 11337985
TI  - Bovine milk gangliosides: changes in ceramide moiety with stage of lactation.
AB  - The stage of lactation is one of the most important factors that influence milk
      composition. Changes in fatty acids from triacylglycerols and phospholipids have
      already been reported. In this study, we looked for a lactational change in the
      ganglioside lipid moiety since ganglioside contents and patterns vary strongly
      with stage of lactation. Individual gangliosides from four stages were isolated,
      methanolized to cleave the bonds between individual constituents, and derivatized
      for gas-liquid chromatography and gas chromatography/mass spectrometry analyses.
      Ceramide components, both fatty acids (as methyl esters derivatives) and long
      chain bases, were identified and quantified. The results pointed to a marked
      change in ceramide from colostrum to milk that was characterized by a dramatic
      decrease in saturated and the longest-chain fatty acids as well as an increase in
      18:1 and 18:2. The major long-chain base along lactation was a recently described
      structure, 3-ethoxy-15:0 sphinganine. Other new long-chain base structures
      appeared in these gangliosides. All these changes suggest differences in the
      fluidity of the fat globule membrane, reflecting physiological variations in cows
      with respect to milk production.

PMID- 11337986
TI  - Comparative investigation of human stratum corneum ceramides.
AB  - The stratum corneum (SC) requires ceramides, cholesterol, and fatty acids to
      provide the cutaneous permeability barrier. SC lipids can be analyzed by normal
      phase high-performance thin-layer chromatography (HPTLC). However, without
      further analysis, some uncertainty remains about the molecular composition of
      lipids represented by every TLC band of an unknown sample. We therefore analyzed
      each ceramide band further by subjecting the isolated lipids to a direct coupling
      of reversed-phase high-performance liquid chromatography and electrospray
      ionization-mass spectrometry (HPLC/ESI-MS, or LC/MS). LC/MS analysis and ESI
      MS/MS negative ion and collision-induced dissociation experiments revealed that
      ceramide band 4 contained not only N-(omega-OH-acyl)acyl-6-OH-sphingosine,
      Cer(EOH), but also N-(alpha-OH-acyl)-sphingosine. Band 5 exclusively contained N
      acyl-6-OH-sphingosine. Our results demonstrate the benefit of LC/MS analysis for
      selective identification of human SC ceramides. Moreover, the combination of
      HPTLC for pre-separation and LC/MS for identification of lipids is an even more
      powerful tool for detailed ceramide analysis.

PMID- 11337988
TI  - Changes in conjugated linoleic acid composition within samples obtained from a
      single source.
AB  - Conjugated linoleic acid (CLA; 9c,11t-18:2) and CLA isomers have been reported,
      in animals, to exhibit a variety of health-related benefits. Silver ion high
      performance liquid chromatography (Ag-HPLC) was found to provide better
      resolution of the isomers than gas chromatography. Most commercially available
      samples of CLA, prepared by base-catalyzed isomerization of linoleic acid (9c,12c
      18:2), are composed of mixtures of four major isomers. While these isomers have
      been characterized, we found significant changes in CLA isomer rations within
      samples obtained from the same producer/commercial supplier over a period of 1.5
      yr. In the first sample, the four cis/trans isomers (8t,10c-18:2, 9c,11t-18:2,
      10t,12c-18:2 and 11c,13t-18:2) were present in a ratio of approximately 1:2:2:1,
      while in the second sample they were present in almost equal proportions. If
      indeed certain daily levels of CLA intake are required to produce suggested
      health benefits in humans, changes in concentrations of specific CLA isomers
      could significantly impact these effects. Care must be taken to analyze the CLA
      used in human and animal studies.

PMID- 11337989
TI  - A new delta 7-polyunsaturated fatty acid in Taxus spp. Seed lipids,
      dihomotaxoleic (7,11-20:2) acid.
AB  - A previously undescribed fatty acid, all-cis 7,11-20:2 (dihomotaxoleic acid,
      DHT), has been characterized by gas chromatography-mass spectrometry as being
      present (approximately 0.1%) in seed oils of two Taxaceae containing high levels
      (11-16%) of taxoleic acid (all-cis 5,9-18:2). This compound was absent from oils
      of 10 other conifer genera, as well as from one member of Taxaceae containing
      very low amounts of taxoleic acid, suggesting that DHT is a taxoleic acid
      elongation product.

PMID- 11337990
TI  - Do privacy regs go too far? HIPAA: what the final regulations mean to Georgia's
      hospitals.

PMID- 11337987
TI  - Optimization of methods and treatment conditions for studying effects of fatty
      acids on cell growth.
AB  - Antiproliferative properties of molecular regulators of lipid metabolism have
      been increasingly studied during recent years. Discussion is ongoing concerning
      optimal treatment conditions and assays used for monitoring proliferation and
      cytotoxicity. The objective of the present work was to optimize methods and
      treatment conditions used for studying antiproliferative effects of fatty acids
      and analogs, represented by palmitic acid (PA) and the beta-oxidation-restricted
      fatty acid analog tetradecylthioacetic acid (TTA), in rat (BT4Cn) and human
      (D54Mg and GaMg) glioma cell lines. Changes in [3H]thymidine incorporation
      preceded changes in cell number in TTA-treated glioma cell cultures, and the
      growth inhibition was more significantly expressed by [3H]thymidine incorporation
      than cell number. Addition of bovine serum albumin decreased cellular fatty acid
      uptake and reduced the effects of TTA and PA on [3H]thymidine incorporation.
      Determination of the antiproliferative effect of TTA in BT4Cn cells by MTT
      conversion and [3H]thymidine incorporation yielded concordant results. TTA
      mediated reduction in cell number corresponded to reduction in cellular protein
      and total DNA content in BT4Cn cells. Reduced growth potential in TTA-treated
      multicellular D54Mg and GaMg spheroids supported the findings from monolayer
      cultures. In conclusion, cell density, treatment period, fatty acid
      administration, and methods for growth determination may profoundly influence the
      outcome of cell growth experiments. Thus, experimental conditions should be
      carefully controlled when performing cell growth experiments, and effects on cell
      growth should preferably be confirmed by different methods.

PMID- 11337991
TI  - "In sickness and health".

PMID- 11337992
TI  - Directors responsible for recognizing "red flags" of systematic fraudulent
      practices.

PMID- 11337993
TI  - One year after disaster, community rallies to support hometown hospital.

PMID- 11337994
TI  - Setting national quality standards for small office surgery practices.

PMID- 11337995
TI  - Organization update form keeps JCAHO aware of major changes.

PMID- 11337996
TI  - Top type is for all accrediteds in 2000.

PMID- 11337997
TI  - Completing H&Ps in the hospital field. History and physical examinations.

PMID- 11337998
TI  - Using performance measurement data in behavioral health.

PMID- 11337999
TI  - Electronic formulary management and Medicaid: maximizing economic efficiency and
      quality of care in the age of electronic prescribing.

PMID- 11338000
TI  - Staffing in the OR. Survey examines how staff are assigned for 19 types of cases.

PMID- 11338001
TI  - How can the Web help us recruit?

PMID- 11338002
TI  - Internship makes room for new grads.

PMID- 11338003
TI  - Complying with patient safety standards.

PMID- 11338004
TI  - Reusable grounding pad found safe, effective in ECRI analysis.

PMID- 11338005
TI  - AAAHC standards stress patient rights.

PMID- 11338006
TI  - Health care a 'maze' in need of reform.

PMID- 11338007
TI  - Ambulatory surgery. Hospitals, ASCs struggle with scarcity of anesthetic drugs.

PMID- 11338008
TI  - Stress caused by minimally invasive cardiac surgery versus conventional cardiac
      surgery: incidence of systemic inflammatory response syndrome.
AB  - The present study was conducted to evaluate the degree of stress in patients
      induced by minimally invasive cardiac surgery (MICS) in comparison with that
      caused by conventional cardiac surgery. We did this by assessing the incidence of
      systemic inflammatory response syndrome (SIRS). A total of 48 adult patients who
      underwent surgery for single valve disease were included in this study, 27 of
      whom underwent conventional surgery and 21 MICS. We evaluated the stress
      inflicted on the patients in these two groups by analyzing the duration and
      degree of SIRS and the level of C-reactive protein (CRP). SIRS was assessed by
      measuring body temperature, heart rate, respiratory rate, and white blood cell
      counts. There were no significant differences in the operating times, perfusion
      times, or aorta clamp times between the two groups; and the mean volume of blood
      transfusion did not differ significantly either. There was no significant
      difference in the incidence of SIRS or the mean duration of SIRS between the two
      groups. The CRP levels did not differ significantly between the two groups. Thus
      although MICS is superior to conventional cardiac surgery in that only a small
      skin incision is required, the stress experienced by the patient may be the same
      as that experienced by the patient undergoing conventional cardiac surgery.

PMID- 11338009
TI  - Changes in venous hemodynamics after superficial vein surgery for mixed
      superficial and deep venous insufficiency.
AB  - The purpose of this study was to determine the hemodynamic changes after
      superficial vein surgery in patients with mixed superficial and deep venous
      insufficiency (MVI). Between July 1996 and June 1998, all patients with MVI
      together with saphenofemoral reflux were evaluated prospectively with air
      plethysmography (APG) and duplex scanning before and 1 month after superficial
      vein surgery. Saphenofemoral flush ligation without stripping was performed with
      multiple small incisions for avulsion of varicosities. Seventy-eight patients
      with 102 operated limbs were included for analysis. The venous filling index
      (VFI), ejection fraction (EF), and residual volume fraction (RVF) improved
      significantly after superficial vein surgery (mean VFI 5.99 +/- 3.39 vs. 1.82 +/-
      1.21 ml/s, p < 0.001; mean EF 48.39% +/- 11.74% vs. 52.78% +/- 14.33%, p < 0.05;
      mean RVF 49.80% +/- 11.18% vs. 36.19% +/- 12.98%, p < 0.001, respectively, before
      and after operation). The proportion of limbs with deep venous incompetence on
      duplex scanning at more than one site decreased from 70% to 44% after operation.
      The mean number of sites with deep venous incompetence decreased from 2.14 +/-
      0.96 to 1.52 +/- 1.21 after operation (p < 0.001). In conclusion, superficial
      vein surgery resulted in significant improvement in hemodynamic parameters in
      limbs with MVI. There was also abolition of deep venous reflux after superficial
      vein surgery alone. Superficial vein surgery should be the first line of
      treatment in limbs with MVI, with deep vein reconstructive surgery reserved for
      those not responding to superficial vein surgery.

PMID- 11338010
TI  - Clinical characteristics and prognosis of patients with hepatoblastoma.
AB  - Hepatoblastoma is a rare pediatric malignancy that frequently appears in an
      advanced unresectable stage. Improved resectability and survival rate have been
      reported with the help of neoadjuvant chemotherapy. Between January 1987 and June
      1995 a series of 20 patients were managed with a diagnosis of hepatoblastoma. The
      median age at diagnosis was 13 months (2 months to 7 years 10 months) with a
      male/female ratio of 13:7. Chemotherapy effectively reduced the tumor volume
      (with statistical significance: p = 0.008) and was able to convert seven of nine
      initially unresectable tumors (78%) to resectable ones. Altogether, 14 operations
      were done, 12 radical and 2 palliative, with or without adjuvant chemotherapy.
      The whole population was followed for a median duration of 33 months; and the
      median survival for the whole group was 26 months. The curative resection group
      displayed a 5-year survival rate of 61.1%, but none in the noncurative group
      survived more than 13 months (p = 0.0001). In the univariate analysis for
      prognostic factors, large tumor size at diagnosis and the absence of
      thrombocytopenia were associated with poor survival, but these differences were
      not statistically significant. Pure fetal histology was not associated with
      better prognosis. In this new era of neoadjuvant chemotherapy, the optimal
      management strategy for hepatoblastoma is still debated, with radical surgical
      resection at the earliest possible time being the final goal. For now an
      individualized approach appears to be the protocol of choice.

PMID- 11338011
TI  - Liver metastatic model for human gastric cancer established by orthotopic tumor
      cell implantation.
AB  - We have established an orthotopic implantation model that is highly metastatic to
      the liver. A human gastric carcinoma cell line, AZ521, with low capacity for
      liver metastasis was implanted as a single-cell suspension in the stomach of nude
      mice. The tumor cells derived from a few liver metastatic foci were subsequently
      implanted orthotopically, and we established a cell line, AZH5G, by repeating the
      in vivo stepwise selection method. This metastasizing line (AZH5G) developed
      liver metastasis in seven of eight (87.5%) cases, whereas parental AZ521
      developed in 3 of 20 (15.0%). The in vitro growth activities of AZH5G were lower
      than that of AZ521, although the in vivo tumorigenicity of AZH5G was clearly
      higher than that of AZ521. Motility assays demonstrated higher motility of AZH5G
      than of AZ521. Flow cytometric analysis demonstrated that the expression of alpha
      6-integrin significantly decreased in AZH5G (4.9% +/- 4.1%) compared to in AZ521
      (17.7% +/- 8.1%) (p < 0.05). The adhesive activity of AZH5G cells to laminin was
      lower than that of AZ521 cells. In contrast, the adhesive activity of AZH5G cells
      to fibronectin was clearly higher than that of AZ521 cells. These findings
      suggested that changes in the expression of integrins on the cell surface might
      play an important role in metastatic ability. This well characterized line and
      its in vivo experimental model should be useful to investigate the mechanisms of
      liver metastasis and to develop a new therapeutic approach for human gastric
      cancer.

PMID- 11338012
TI  - Inguinal hernia repair in the new millennium: plug and patch repair with local
      anesthesia.
AB  - Plug and patch repair is a safe, economic method for repairing inguinal hernias,
      with patient comfort comparable to that with laparoscopic hernia repair. The
      technique is simple to perform under local anesthesia and easily learned without
      a learning curve. Complications are rare, and recovery and return to work are
      rapid. After performing plug and patch repair on 400 patients with a follow-up
      examination rate of 93% and a median postoperative observation time of 42 months,
      we have recorded a recurrence rate of only 0.25%.

PMID- 11338013
TI  - Effect of sucrose on collagen metabolism in keloid, hypertrophic scar, and
      granulation tissue fibroblast cultures.
AB  - Sucrose has been used to treat wounds with excellent results and with minimal
      abnormal scarring. In this study the effects of sucrose on collagen metabolism in
      fibroblast culture was evaluated. Sucrose (5.5, 15, or 25 mM) was added to
      granulation tissue, hypertrophic scar, and keloid fibroblast cultures, mRNA
      levels and procollagen aminopropeptides for type I and III collagens in cell
      culture medium were studied. Sucrose decreased mRNA levels for pro alpha 1(I) and
      pro alpha 1(III) collagens in fibroblast cultures derived from hypertrophic scar
      and keloid. In normal granulation tissue fibroblast cultures, 5.5 mM sucrose
      increased mRNA levels for pro alpha 1(I) and pro alpha 1(III) collagen, and
      higher concentrations decreased them. The synthesis of type I collagen decreased
      dose-dependently in all cell strains, whereas the synthesis of type III collagen
      decreased only in granulation tissue fibroblasts. To conclude, in vitro high
      concentrations of sucrose down-regulate both collagen gene expression and
      synthesis in normal granulation tissue fibroblasts, whereas in fibroblasts
      derived from abnormal scar sucrose down-regulates only type I collagen gene
      expression and synthesis, changing the pattern of collagen metabolism toward
      normal.

PMID- 11338014
TI  - Peritoneal regeneration after implant of a composite prosthesis in the abdominal
      wall.
AB  - Prosthetic materials currently used to repair abdominal wall defects occasionally
      must be placed in direct contact with the visceral peritoneum. The prosthesis
      peritoneum interface is the site of several possible problems, including the
      formation of adhesions and erosion of the intestinal loops, which may lead to the
      formation of fistulas. This investigation was designed to compare the behavior of
      two prosthetic biomaterials in composite form at the level of the peritoneum.
      Defects (7 x 5 cm) were created in the abdominal wall of 18 white New Zealand
      rabbits weighing approximately 2500 g. The defects (involving aponeurotic and
      muscular planes and the parietal peritoneum) were repaired with polypropylene
      (PL) + ePTFE (Preclude dura substitute) or Parietex composite (PC) prostheses.
      The prostheses were secured to the edges of the defect by continuous PL sutures
      interrupted at the corners of the implant. Three study groups were established
      according to the type of implant: group I (n = 6) (controls)--PL; group II (n =
      6)--PL + ePTFE; and group III (n = 6)--PC. The animals were sacrificed 14 days
      after implant, and the prostheses were examined by light microscopy and scanning
      electron microscopy (SEM). The formation of adhesions at the prosthesis-visceral
      peritoneum interface were quantified according to a protocol previously described
      by us. The biomechanical resistance of the implant was evaluated using strips
      comprising prosthetic material and anchorage tissue. The Mann-Whitney U-test was
      used to compare data corresponding to each group. There was no postimplant
      mortality. No infection or rejection of the prosthesis was observed in any of the
      animals. Firm adhesions were detected in the PL implants, whereas in the PL +
      ePTFE and PC implants the adhesions were loose. The mean prosthetic surface areas
      covered by adhesions were 7.67, 0.10 and 0.19 cm2 for groups I, II, and III,
      respectively, showing a significant difference between values corresponding to
      groups I and II and to groups I and III (p < 0.05). Comparison of values recorded
      for groups II and III yielded no significant difference (p > 0.05). In groups II
      and III, the neoperitoneum was homogeneous and composed of organized and
      vascularized connective tissue covered by a mesoendothelium that was interrupted
      by accumulations of fibroblasts and white blood cells. In contrast, a
      disorganized neoperitoneum of rough texture was observed in the group I
      specimens. At times, areas of hemorrhage and necrosis corresponding to the sites
      of adhesion formation could be observed. Resistance to traction of composite
      implants (mean +/- SD: 15.72 +/- 1.32 and 15.89 +/- 2.73) was similar to that of
      the PL implants (15.03 +/- 2.92) (Mann-Whitney U-test, p < 0.05). It may be
      concluded that (1) composite prostheses show optimum behavior in terms of
      adhesion formation at the prosthesis-visceral peritoneum interface; (2) the
      neoperitoneum formed after the implant of a composite prosthesis almost
      physically and functionally replaces the normal peritoneum; (3) a significantly
      greater degree of peritoneal regeneration is achieved after implant of a PC
      prosthesis; and (4) there was no significant difference regarding biomechanical
      resistance between PL prostheses and PL + ePTFE and Parietex composites.

PMID- 11338015
TI  - Benito Mussolini (1883-1945): assassination attempt at International Society of
      Surgeons Convention, rise to power, medical history, and final days.

PMID- 11338016
TI  - Place of video-thoracoscopy in thoracic surgical practice.
AB  - The advent of video-endoscopy revolutionizes the practice of surgery. Within a
      short span of time, video-assisted thoracic surgery (VATS) has become an
      acceptable approach to a wide range of thoracic procedures. The use of VATS as a
      diagnostic modality is now well established. For therapeutic procedures, VATS has
      also been generally accepted for the treatment of such conditions as primary
      spontaneous pneumothorax, loculated effusions, thoracodorsal sympathectomy, and
      resection of simple mediastinal cysts. Its roles in more complex procedures such
      as thymectomy and anatemic lung resections, however, remain poorly defined at
      present, even though the existing intermediate-term results are encouraging. VATS
      is still in evolution. Miniaturization of instruments promises to reduce access
      induced trauma even further. On the other hand, attention to cost-containment is
      essential if VATS is to be applicable to patients in developing countries.
      Technology will continue to change. Carefully conducted clinical trials should
      precede the general acceptance of any new technology, no matter how attractive it
      may appear initially.

PMID- 11338017
TI  - Modern anesthetic techniques for thoracic operations.
AB  - Continuing advances in anesthesiology enable surgeons to perform more and more
      complex operations. Nowhere is this relation more important than for the patient
      undergoing thoracic surgery. Specialized anesthetic techniques including safe
      lung separation, the maintenance of oxygenation during selective one-lung
      ventilation, and effective postoperative analgesia allow procedures such as lung
      volume reduction surgery and lung transplantation to be performed routinely. This
      paper reviews modern clinical practices in the field of thoracic anesthesia.

PMID- 11338018
TI  - Advances in the staging of intrathoracic malignancies.
AB  - Conventional staging of lung and esophageal tumors has consisted of a thorough
      history and physical examination, screening laboratory studies, computed
      tomography, and radionuclide imaging. Newer modalities including positron
      emission scanning, endoscopic ultrasonography, minimally invasive surgery
      (laparoscopy and thoracoscopy), and immunohistochemical staining of lymph node
      tissue. The role of these techniques are subject to much current debate, and they
      may ultimately add information that is valuable for staging and optimally
      treating patients with intrathoracic malignancies.

PMID- 11338019
TI  - Targets for molecular intervention in multistep pulmonary carcinogenesis.
AB  - Lung cancers are a leading cause of mortality worldwide, and most of these
      neoplasms are directly attributable to tobacco abuse. Recent studies have begun
      to elucidate molecular mechanisms of multistep aero-digestive tract
      carcinogenesis, revealing novel targets for intervention in lung cancers and
      their precursor lesions. This review summarizes the molecular biology of lung
      cancers in relation to the prognosis and treatment of patients with these
      neoplasms.

PMID- 11338020
TI  - Appropriate surgical treatment of resectable non-small-cell lung cancer.
AB  - Patients with early-stage non-small-cell lung cancer (NSCLC) should be treated
      with complete surgical resection whenever possible. Incomplete resections do not
      cure, and the optimal pulmonary resection is anatomic lobectomy. Limited
      resections (wedge resection and segmentectomy) are associated with a threefold
      increase in local recurrence, which translates into decreased survival. The
      addition of mediastinal lymph node dissection produces the best pathologic
      staging but has never been shown to improve survival. Resections can be performed
      through a variety of incisions and even using minimally invasive techniques, but
      posterolateral thoracotomy seems to provide the best exposure and is used most
      frequently. Adjuvant radiotherapy in both the preoperative and postoperative
      settings does not improve survival in patients with resected NSCLC. Similarly,
      postoperative chemotherapy cannot be advocated in these patients based on the
      current data. Improved survival has been demonstrated in the randomized setting
      for patients with locally advanced, resectable disease (N2) using preoperative
      (induction) chemo(radio)therapy, but the numbers are small. Patients with this
      stage of NSCLC should be enrolled in induction therapy protocols whenever
      possible to confirm the efficacy of this approach.

PMID- 11338021
TI  - What is appropriate treatment for carcinoma of the thoracic esophagus?
AB  - Recent advances in the treatment of esophageal cancer have yielded a variety of
      new options for management of this highly lethal disease. Various approaches to
      surgical resection have been proposed. Chemotherapy and radiotherapy with or
      without surgery have been tested in numerous trials, the results of which are
      often conflicting and confusing for clinicians. The changing epidemiology of the
      disease between East and West adds to the controversy. In this review, the
      authors address some of the more controversial debates. The following questions
      are asked: What is the appropriate approach for surgical resection? What is the
      appropriate extent of resection? Is multimodality treatment appropriate for
      esophageal cancer?

PMID- 11338022
TI  - Transhiatal esophagectomy for treatment of benign and malignant esophageal
      disease.
AB  - Since our initial 1978 report, we have performed transhiatal esophagectomy (THE)
      in 1085 patients with intrathoracic esophageal disease: 285 (26%) benign lesions
      and 800 (74%) malignant lesions (4.5% upper, 22% middle, and 73.5% lower
      third/cardia). THE was possible in 97% of patients in whom it was attempted;
      reconstruction was performed at the same operation in all but six patients. The
      esophageal substitute was positioned in the original esophageal bed in 98%,
      stomach being used in 782 patients (96%) and colon in those with a prior gastric
      resection. Hospital mortality was 4%, with three deaths due to uncontrollable
      intraoperative hemorrhage. Major complications included anastomotic leak (13%),
      atelectasis/pneumonia prolonging hospitalization (2%), recurrent laryngeal nerve
      paralysis, chylothorax, and tracheal laceration (< 1% each). There were five
      reoperations for mediastinal bleeding within 24 hours of THE. Intraoperative
      blood loss averaged 689 ml. Altogether, 78% of the patients had no postoperative
      complications. Actuarial survival of the cancer patients mirrors that reported
      after transthoracic esophagectomy. Late functional results are good or excellent
      in 80%. Approximately 50% have required one or more anastomotic dilatations. With
      intensive preadmission pulmonary and physical conditioning, use of a side-to-side
      staple technique (which has reduced the cervical esophagogastric anastomotic leak
      rate to less than 3%), and postoperative epidural anesthesia, the need for an
      intensive care unit stay has been eliminated and the length of hospital stay was
      reduced to 7 days. We concluded that THE can be achieved in most patients
      requiring esophageal resection for benign and malignant disease and with greater
      safety and less morbidity than the traditional transthoracic approaches.

PMID- 11338023
TI  - Mediastinal tumors: diagnosis and treatment.
AB  - Mediastinal tumors are uncommon and often asymptomatic if benign. Tumors have a
      predilection for arising in one of three mediastinal compartments; anterior,
      middle, or posterior. If symptoms are present, they are usually compressive in
      origin. Computed tomography is almost always the imaging modality of choice.
      Benign-appearing lesions are usually resected for cure. Malignant-appearing
      lesions usually require biopsy by the least invasive route appropriate for the
      suspected tumor type.

PMID- 11338024
TI  - Treatment of malignant mesothelioma.
AB  - Malignant pleural mesothelioma (MPM) is a rare tumor that predominantly afflicts
      men over 50 years of age. Nearly 3000 MPMs are reported annually in the United
      States with the incidence expected to rise into the new millenium. Over the past
      40 years, MPM has been unequivocally linked to asbestos exposure worldwide.
      Recently, however, a new theory on the carcinogenesis of this tumor has been
      proposed with the isolation of a simian virus (SV 40)-like gene sequence in
      mesothelioma tumor cells. The clinical presentation of MPM is variable, although
      most patients typically present with dyspnea, chest pain, or pleural effusion.
      Obtaining a diagnosis of MPM has been greatly assisted by video-assisted surgery
      and the use of immunohistochemistry and electron microscopic techniques, which
      help distinguish MPM from other tumor pathologies such as adenocarcinoma.
      Computed tomography and magnetic resonance imaging have been also useful for
      determining tumor burden and resectability. Traditionally, strategies for the
      treatment of MPM have included supportive care, surgery, radiotherapy, and
      chemotherapy. Survival with supportive care alone ranges between 4 and 12 months.
      Single-modality therapy using traditional approaches (surgery, radiotherapy,
      chemotherapy) alone has failed to improve patient survival significantly.
      Recently, results using a multimodality approach have been favorable. In
      particular, cytoreductive surgery (pleuropneumonectomy) followed by sequential
      chemotherapy and radiotherapy have demonstrated improved survival, especially for
      patients with epithelial histology, negative resection margins, and no metastases
      to extrapleural lymph nodes. Innovative therapies such as the use of
      photodynamic, targeted cytokines and gene therapy are currently being
      investigated for management of MPM.

PMID- 11338025
TI  - Surgical treatment of chest wall tumors.
AB  - Chest wall tumors have long represented challenging clinical entities for
      surgeons. Until recently, incorrect diagnosis, incomplete resection, or inability
      to perform successful reconstruction of large thoracic wall defects led to high
      rates of perioperative morbidity and mortality. The latter were primarily
      associated with infections of the pleural cavity, respiratory failure, and
      paradoxical breathing. The long-term prognosis was also poor owing to a high
      percentage of local relapse. During the same operating procedure wide resection
      and reconstruction of the thoracic wall are performed successfully. Improvement
      of the prognosis reported in large series of patients with resection leads to
      surgical treatment being considered the best option for primary tumors and for
      selected secondary tumors of the chest wall. Because positive margins are the
      most important risk factor for local recurrence, adequate margins of healthy
      tissue surrounding the tumors have a considerable impact on disease-free and
      overall survival. Involvement of ribs, sternum, superior sulcus, or spine is not
      considered a technical limitation to surgical resection. Nowadays correct
      management cannot be precluded by tumor size, site, or contiguous structure
      involvement because concurrent reconstruction with prosthetic materials and
      myocutaneous flaps is feasible. Surgery provides the best chance of cure in
      patients with chest wall tumors. Therefore the surgical strategy must be based on
      the features of the individual's disease.

PMID- 11338026
TI  - Lung volume reduction surgery for chronic obstructive pulmonary disease: where do
      we stand?
AB  - Lung volume reduction surgery (LVRS) is a promising new treatment for selected
      patients with moderate to severe symptoms of emphysema. Medical management,
      including pulmonary rehabilitation, has been shown to reduce oxygen requirements
      during exercise and probably to reduce hospitalization for patients with severe
      emphysema, but it does not improve pulmonary function. By improving the elastic
      recoil of the lung, LVRS is the first treatment to demonstrate substantial
      improvement in pulmonary function and quality of life for selected patients with
      emphysema. The most important selection factor for LVRS is the presence of a
      heterogeneous pattern of emphysema. Because it is found in only 20% of patients
      with emphysema, only a small number of patients are candidates for the procedure.
      Published reports indicate that the optimal operative technique appears to be a
      bilateral staple operation during a single anesthetic. This procedure offers a
      68% chance of oxygen independence, 85% chance of prednisone independence, and 60%
      to 70% improvement in pulmonary function for patients with an upper lobe
      distribution of emphysema. The long-term benefits of the procedure are currently
      unknown, so several randomized, prospective studies are now comparing LVRS with
      maximal medical management.

PMID- 11338027
TI  - Lung transplantation versus lung volume reduction as surgical therapy for
      emphysema.
AB  - There are currently two surgical therapies aimed at crippling, end-stage
      emphysema: lung transplantation and lung volume reduction surgery (LVRS).
      Unfortunately, most emphysema patients are poor candidates for any surgical
      intervention. The authors favor a meticulous selection process in which
      indications and contraindications are considered and the best solution is devised
      for each patient. Patients with ideal circumstances for LVRS--hyperinflation,
      heterogeneous distribution of disease, FEV1 of more than 20%, and normal PCO2-
      are offered LVRS. Patients with diffuse disease, low FEV1, hypercapnia, and
      associated pulmonary hypertension are directed toward transplantation. LVRS has
      not been a satisfactory option for patients with a1-antitrypsin deficiency, and
      we prefer a transplant in most of these patients. With these considerations, we
      find that few patients are serious candidates for both procedures. Combinations
      of lung volume reduction and lung transplantation, simultaneously or
      sequentially, are possible but rarely necessary.

PMID- 11338028
TI  - Living donor lung transplantation.
AB  - Since 1993 a total of 101 living-donor bilateral lung transplants have been
      performed with acceptable results when compared with those utilizing cadaveric
      lung grafts. Though most recipients were patients with cystic fibrosis who were
      rapidly deteriorating, the indications for live-donor lung transplantation have
      been expanded to include some cystic fibrosis patients in a more elective
      setting, as well as select patients with other end-stage pulmonary diseases. One
      year Kaplan-Meler recipient survival is 72%. Seventy-six percent of deaths occur
      within the first 2 months after transplantation. The most common cause of death
      is infection, which accounts for 62% of the 1-year mortality rate. The incidence
      of rejection is 0.8 episodes per patient. Thirty percent of rejection episodes
      are unilateral, and most tend to be mild. Altogether, 203 patients have undergone
      donor lobectomy, with a mean age of 37 +/- 12 years (range 18-56 years).
      Operations included left lower lobectomy (102 patents), right lower lobectomy (97
      patients), and right middle and lower lobectomy (4 patients). There has been no
      donor mortality. Postoperative Rand 36 Question Quality of Life scores, rating
      physical function, social functioning, and role limitation due to physical and
      emotional health, are well over 92 (of a possible score of 100). Eighty-five
      percent of donors said that their health was no different or improved since
      donation.

PMID- 11338029
TI  - Successful treatment of immune thrombocytopenic purpura (ITP) with splenectomy.

PMID- 11338030
TI  - Excellent results are possible with the use of intravenous cholangiography to
      predict the presence common bile duct (CBD) stones.

PMID- 11338031
TI  - Our experience of more than 1000 thyroidectomies in a tertiary care referral
      center.

PMID- 11338032
TI  - Gradual ductal dilation and stent placement through a T-tube tract.

PMID- 11338033
TI  - Multidisciplinary team interested in the treatment of pulmonary arteriovenous
      fistulas or malformations (PAVFs).

PMID- 11338034
TI  - Prescribing limitations.

PMID- 11338035
TI  - Fluoridation jinks.

PMID- 11338036
TI  - Assessing competence in surgical dentistry.
AB  - The growing demand for assessment in all aspects of surgical competencies will
      inevitably embrace the whole of dental surgery. The aim of this paper is to
      review the literature and discuss some of the issues that will have to be
      addressed as objective assessment of the surgical dentists' skills is introduced.
      The paper reviews what is meant by competence and how we assess it, with
      particular emphasis on practical and technical skills. Specific methodologies for
      assessing competence are described including, as illustrations, two means of
      assessing the removal of lower wisdom teeth. The evaluation of competence in the
      workplace is discussed together with the difficulty in assessing important
      attributes such as attitude. It concludes that the assessment of competence is a
      valuable tool in its own right and a means of demonstrating to the public the
      continuing commitment of the profession to the highest possible standards.
      However assessment will be very time consuming and to be worth while we must
      ensure that it is done in a way that produces clear and unambiguous benefits and
      solves real problems.

PMID- 11338037
TI  - Bilateral hyperplasia of the mandibular coronoid processes associated with the
      nevoid basal cell carcinoma syndrome in an Italian boy.
AB  - In this report we present a subject affected by nevoid basal cell carcinoma
      syndrome (NBCCS), showing also bilateral mandibular coronoid processes
      hyperplasia, a hitherto unreported association. Our observation of bilateral
      hyperplasia of the mandibular coronoid processes in a boy with NBCCS may prompt a
      retrospective and prospective review of other patients affected by this syndrome
      in order to establish if this anomaly is part of it.

PMID- 11338038
TI  - The role of team dentistry in improving access to dental care in the UK.
AB  - The role of professionals complementary to dentistry (PCDs) in improving access
      to NHS primary dental care is discussed. The pattern of under-supply of dentists
      in poor socio-economic areas is highlighted and identified, in drawing a parallel
      to the workings of primary medical teams, as a possible area where PCDs could be
      used.

PMID- 11338039
TI  - A look at forensic dentistry--Part 1: The role of teeth in the determination of
      human identity.
AB  - Forensic dentistry can be defined in many ways. One of the more elegant
      definitions is simply that forensic dentistry represents the overlap between the
      dental and the legal professions. This two-part series presents the field of
      forensic dentistry by outlining two of the major aspects of the profession: human
      identification and bite marks. This first paper examines the use of the human
      dentition and surrounding structures to enable the identification of found human
      remains. Conventional and novel techniques are presented.

PMID- 11338040
TI  - Tooth surface pH during drinking of black tea.
AB  - OBJECTIVES: To investigate the composition of black tea in terms of its erosive
      potential. To determine the pH profile at the palatal surface of anterior and
      posterior sites of the dentition after drinking black tea. METHODS: Tea solution
      was analysed for its pH and anion composition to provide information on its acid
      content. A group of ten healthy subjects, aged 21-23 years were monitored for
      tooth surface pH on the palatal aspects of the maxillary anterior dentition and
      the maxillary molar dentition after drinking tea using a micro-pH electrode
      mounted on a vinyl splint. RESULTS: The pH of the tea solution was 4.9 and the
      major anions detected were oxalate and citrate. Tooth surface pH monitoring
      indicated that only small decreases in pH of less than 1 pH unit were observed
      after drinking tea and the minimum mean pH reached was 5.45. Maximum decrease in
      pH was observed after 20-25 seconds and resting pH levels were restored within
      approximately 2 minutes after drinking. CONCLUSION: The pH and anion profile of
      black tea are indicative of low acid composition. The very small pH decreases
      observed at the tooth surface after drinking tea indicate that it may be safely
      recommended as a substitute for more acidic drinks as a part of preventive
      measures for dental erosion.

PMID- 11338041
TI  - An assessment of the incidence of punctures in latex and non-latex dental
      examination gloves in routine clinical practice.
AB  - OBJECTIVE: To investigate the puncture resistance of a recently introduced non
      latex, nitrile dental glove in comparison with a latex glove worn during routine
      clinical dental procedures. SETTING: Dentists in general dental practice working
      within the UK during 1999. SUBJECTS AND METHODS: 2,020 gloves worn by five
      general dental practitioners were examined for punctures following standard
      clinical use by a water inflation method. Procedures undertaken during glove
      usage and length of time worn were recorded. RESULTS: Following clinical use,
      1.9% of the latex gloves and 5.3% of the nitrile gloves had punctures, a
      statistically significant difference (P < 0.0001). The puncture resistance of the
      nitrile gloves was superior to the puncture resistance of previously tested worn
      non-latex (vinyl) gloves. There was no evidence of a statistically significant
      difference between operators for the percentage or incidence of punctured gloves
      (P = 0.787) after correcting for glove type. No statistically significant
      difference was noted between incidence of puncture in the control, unused gloves
      (n = 200 for each type) and the gloves examined following clinical use (P = 0.907
      for nitrile, P = 0.613 for latex). CONCLUSION: No increase in the number of
      punctures was noted following clinical use for either glove type. This could be
      considered to indicate good puncture resistance of the gloves tested in clinical
      use.

PMID- 11338042
TI  - Caries among 3-year-olds in greater Manchester.
AB  - OBJECTIVE: To measure the prevalence of caries, including nursing caries, amongst
      3-year-old children in three districts of Greater Manchester in the North West of
      England. DESIGN: A cross-sectional survey of 762 randomly selected 3-year-old
      children using the dmft and dmfs indices. Three definitions of nursing caries
      were used in order to assess the varying prevalence of the disease according to
      which definition was applied. SUBJECTS: Children, aged 36-48 months, attending
      day nurseries, play groups and nurseries attached to primary schools were
      examined by three trained examiners under standardised conditions in three health
      districts in Greater Manchester. A random selection process was used to produce a
      quota sample to reflect the balance of childcare provision in each district.
      RESULTS: The overall proportion of children affected by general caries was 32%.
      The mean dmft score was 1.4 (sd = 2.8) and the mean dmfs was 2.8 (sd = 7.3).
      There were significant differences across the three districts. The prevalence of
      nursing caries varied widely when differing definitions of types were applied;
      1.6% of the children had nursing caries according to the narrow definition, 7.2%
      showed the wider definition type and 9.8% had nursing caries of the broadest
      definition. In total 19% of children had caries which affected their upper
      incisors. Children of Asian origin had the highest levels of nursing and overall
      caries. CONCLUSIONS: Caries is a widespread problem in some very young children
      in the districts involved. Caries of upper anterior teeth contributes
      significantly to the overall level of caries in each of the localities in
      question. The prevalence of nursing caries is highly dependent on the case
      definition used.

PMID- 11338043
TI  - The Structured Clinical Operative Test (SCOT) in dental competency assessment.
AB  - INTRODUCTION: This paper describes a method of assessment of invasive clinical
      procedures which are currently being devised, and which are perceived to be a
      method that may be used to complement OSCEs in overall clinical skills
      assessment. OBJECTIVE: The objective of the Structured Clinical Operative Tests
      (SCOT) is to introduce a greater level of objectivity to the assessment of
      operative clinical skills. Invasive or irreversible clinical operative procedures
      from a large part of dental undergraduate training and are by their very nature
      precluded from OSCE scenarios. It is also important to test intraoperative
      skills, communication skills and contingency management, and performance of these
      with awareness of the psychosocial context and ethical framework. The paper
      describes the use of checklists in the monitoring of clinical operative skills in
      a more authentic clinical situation using the SCOT. FORMATIVE ASSESSMENT:
      Continuous assessment should a) record achievement of competency in as objective
      a manner as possible and b) should encourage continuous self-evaluation. In the
      SCOT the students reflect on their clinical performance and in consultation with
      their supervisors record their plans to improve their competence in that skill or
      procedure in the future. This is done immediately on completion of a clinical
      task while the experience is still fresh in the mind. This encourages deep
      reflective learning as opposed to superficial factual learning which is
      characteristic of the more traditional curriculum, and is described as supervisor
      validated self-assessment. DISCUSSION: The discussion outlines how SCOTs can be
      practically implemented and integrated into the undergraduate curriculum and an
      example of a SCOT is appended to the paper. The scope for using SCOTs in
      postgraduate assessment such as in VT/GPT is also described.

PMID- 11338044
TI  - Sentinel node localization: emerging uses and limitations.

PMID- 11338045
TI  - Gamma probe sentinel node localization and biopsy in breast cancer patients
      treated with a neoadjuvant chemotherapy scheme.
AB  - The aim of this study was to analyse the accuracy of scintigraphic and gamma
      probe sentinel node (SN) localization in breast cancer patients who have been
      submitted to neoadjuvant chemotherapy (NC). Seventy-six patients with single
      breast cancer were included in the study, and were classified into two groups.
      Group 1 consisted of 40 women who had received NC, and Group 2 consisted of 36
      women who did not receive NC. All patients received 111 MBq (3 mCi) of 99Tcm
      nanocolloid in 3 ml, by peritumoural injection. Anterior and lateral thoracic
      scans were obtained 2 h post-injection. The following day (18-24 h post
      injection) the patients underwent surgery and sentinel nodes were localized by
      using a gamma probe. Complete axillary lymph node dissection was performed in all
      patients. Histological analysis included haematoxylin-eosin in all cases and
      immunohistochemistry in 10 cases. In Group 1, SNs were localized in 36/40
      patients, histological analysis was performed in 34 and there were four false
      negatives (22%). In Group 2, SNs were localized in 32/36 patients, histological
      analysis was performed in 29 and there were two false negatives (9%). Predictive
      negative values were 78% and 90% in Groups 1 and 2, respectively. In summary,
      sentinel node localization in breast cancer patients submitted to previous
      neoadjuvant chemotherapy is less accurate than in patients who do not receive
      this therapy. The procedure is not sufficiently accurate to localize the sentinel
      node, thus it cannot be recommended in these patients.

PMID- 11338046
TI  - Patient dosimetry after 131I-MIBG therapy for neuroblastoma and carcinoid
      tumours.
AB  - AIM: The aim of the study was to determine the equivalent total body dose (ETBD)
      using the cytokinesis-blocked micronucleus assay in 22 131 I-meta
      iodobenzylguanidine (131 I-MIBG) therapies (18 neuroblastoma, mean 5097 MBq, SD
      1591; and four carcinoid tumours, mean 7681 MBq, SD 487). The results are
      correlated with the total body radiation dose according to the Medical Internal
      Radiation Dosimetry (MIRD) formalism. METHODS: For each patient, blood samples
      were taken immediately before and 1 week after 131I-MIBG therapy. The first blood
      sample was irradiated in vitro with 60Co gamma-rays to determine the dose
      response curve. Micronuclei were scored in 1000 binucleated cells. By using the
      dose-response curve the ETBD was derived from the increase in micronuclei after
      131I-MIBG therapy (second blood sample). Based on three consecutive biplanar
      scans taken at 3, 6 and 9 days post-administration respectively, the total body
      dose following the MIRD formalism was calculated. RESULTS: The micronucleus assay
      was evaluable in only 14 out of 22 131I-MIBG therapies due to cell division
      inhibition caused by previous chemotherapy treatments and lymphocyte dilution due
      to blood transfusions given shortly after 131I-MIBG therapy. For these 14
      therapies, the mean micronucleus yield after 131I-MIBG therapy was significantly
      increased (P < 0.01) with a mean of 92 (SD 77) for neuroblastoma patients and
      with a mean of 35 (SD 8) for carcinoid patients. The increase observed in the
      present study is greater than previously observed after 131I therapy and 89Sr
      therapy but much lower than after external beam radiotherapy. For all patients
      treated with multiple therapies, the initial increase in micronucleus yield had
      at least partially recovered by the time of the next therapy. This might be
      explained by an increased turnover of lymphocytes. A mean ETBD of 0.95 Gy (SD
      0.55) for neuroblastoma patients and a mean of 0.46 Gy (SD 0.09) for carcinoid
      patients was calculated. A reasonable correlation (R = 0.87) between the ETBD and
      the MIRD dose was obtained. The slope value of 0.75 can be explained by the low
      dose rate effect. CONCLUSIONS: The observation in the present study of important
      inter-individual variability in the total body dose, with the possibility of high
      dose values, suggests the necessity of individual dosimetry when administering
      131I-MIBG therapy, especially considering that generally more than one therapy is
      given to each patient.

PMID- 11338047
TI  - A comparison of radiopharmaceutical agents used for the diagnosis of pulmonary
      embolism.
AB  - Radioactive gas or technetium-99m aerosols are used to perform pulmonary
      ventilation scintigraphy. The aim of this study was to compare three
      radiopharmaceuticals, Kryptoscan, Technegas and Venticis II, in terms of their
      costs and user preferences rather than on the basis of diagnostic efficacy. For
      each radiopharmaceutical agent, an analysis questionnaire was sent to nuclear
      medicine departments setting out the criteria (and subcriteria) to be assessed:
      diagnosis quality: imaging quality, distribution homogeneity, examination
      procedures and capacity to examine particular patients (e.g. smokers); safety:
      for patient, paramedical and medical staff and the environment; use: availability
      in cases of emergency, ergonomics of the apparatus, simplicity and time of
      preparation. A score, ranging from 0 to 5, and a weighting (importance of one
      criterion with regard to the others) were assigned to each criterion. The direct
      cost of a ventilation (drugs, generator systems, disposable materials) was
      calculated for each radiopharmaceutical agent according to the number of patients
      examined per day (1-6) and the number of examination days per week (2-5).
      Fourteen questionnaires concerning at least two of the products were returned out
      of the 30 mailed. A 'preference score' was calculated using Pharma Decision
      software. The mean score of Kryptoscan was significantly higher than that of
      Venticis II (444 vs. 286, P < 0.001) and higher than the mean score of Technegas
      (444 vs. 344, P < 0.01). For Venticis II and Technegas, the changes in patient
      direct costs were minor and depended on the number of patients per day and the
      number of examination days per week. Respectively, they were: $US 117.66 (5
      patients.day-1; 5 days.week-1) to $US 147.74 (2 patients.day-1; 2 days.week-1)
      and $US 56.60 (6 patients.day-1; 5 days.week-1) to $US 132.08 (2 patients.day-1;
      2 days.week-1). The direct cost of ventilation using Kryptoscan varied only
      according to the number of patients examined per day: $US 104.66 (6 patients.day
      1) to $US 266.47 (2 patients.day-1). This study shows that Kryptoscan appears to
      be preferable for ventilation scintigraphy whenever at least four patients are
      examined daily.

PMID- 11338048
TI  - Dynamics of 'Technegas' deposited in the lung.
AB  - In tomographic Technegas ventilation studies, the deposited aerosol should be
      stable. The aim of this study was to investigate the stability of deposited
      Technegas in severely obstructed patients and in healthy volunteers. Six
      emphysematous patients and five healthy volunteers were studied. Anterioposterior
      (AP) and posterioanterior (PA) dynamic images of ventilation (120 frames, 1
      frame.min-1) were acquired after inhalation of 99mTc-Technegas' in the supine
      position. The time-activity curve of the whole lung showed two phases in the
      emphysematous patients as well as in the healthy volunteers. The activity
      decreased rapidly in the first phase, then reached almost a constant level (the
      second phase) after approximately 50 min. The logarithms of both the first phase
      and the second phase were close to straight lines. The half-time of the first
      phase was approximately 9 min. No systematic differences in 'Technegas' clearance
      rate were found between central regions and peripheral regions and between high
      count rate regions and normal count rate regions. Pertechnegas contamination was
      subsequently detected, and we conclude that the rapid first phase is probably due
      to clearance of Pertechnegas. When stable Technegas is required, we suggest that
      data acquisition should start about 50 min after inhalation.

PMID- 11338049
TI  - Post-elution concentration of 99TcmO4- by a single anion exchanger column: II.
      Preparation and evaluation of jumbo alumina column chromatographic generator for
      99Tcm.
AB  - We report on the preparation and evaluation of a large size (jumbo) alumina
      column (approximately 40 g, 90 x 20 mm) chromatographic generator and post
      elution concentration of 99Tcm using a single column of a weak anion exchanger.
      The generator was eluted with approximately 40 ml of a modified single salt
      buffer solution of 1:1 v/v 0.025 M or 0.05 M NH4OAc:0.7 M AcOH. This eluate was
      then passed through a small column of DEAE cellulose, a common weak anion
      exchanger, to trap 99TcmO4-, which was recovered by elution in 6 ml of normal
      saline. This amounts to a 5- to 7-fold increase in radioactive concentration
      (RAC) of 99Tcm, when compared to the RAC on direct elution with normal saline
      from the same jumbo alumina column generator. The overall yield of 99Tcm was in
      the range of 70-90%. 99Mo breakthrough was 10(-3)-10(-4)%, radiochemical purity
      was > 98%, and chemical purity, in terms of Al and Mo content, < 10 ppm each. The
      compatibility of pertechnetate obtained by this method for preparing 99Tcm
      labelled formulations such as Tc-MDP and 99Tcm-ethyl cysteinate dimer was found
      to be satisfactory. These promising results open up the feasibility of using (n,
      gamma) 99Mo adsorbed on a large (40-60 g) alumina column as a relatively more
      user-friendly source of 99Tcm in comparison to methyl ethyl ketone extraction,
      and as a producer-friendly process in comparison to the zirconium molybdate gel
      method.

PMID- 11338050
TI  - Acute effect of 3-(4-acetamido)-butyrril-lorazepam (DDS2700) on brain function
      assessed by PET at rest and during attentive tasks.
AB  - The aim of this study was to assess, by positron emission tomography (PET), the
      effect on cerebral functional activity of a new lorazepam-gamma-aminobutyric acid
      (GABA) conjugate [3-(4-acetamido)-butyrril lorazepam (DDS2700)]. Ten healthy
      volunteers were studied by PET and [18F]fluoro-deoxy-D-glucose ([18F]FDG) under
      baseline conditions and following the administration of DDS2700. Regional
      cerebral blood flow (rCBF) was measured by PET and 15O-water in three additional
      participants while they performed attentive tasks, before and after drug
      administration. DDS2700 induced a decrease in the regional cerebral metabolic
      rate of glucose (rCMRglu) in the thalamus (-17%), cerebellum (-11%) and caudate
      nucleus (-8%). The observed effects on glucose metabolism were probably related
      to the subjective sedation and tiredness reported by the participants. During the
      attentive tasks, rCBF increased in frontal and temporal regions associated with
      attentional processing of auditory material. These circuits were no longer active
      after DDS2700 administration, while rCBF increased in cingulate cortex,
      occipitoparietal regions, pons and cerebellum. These drug-induced activations
      might be directly related to intervening sleepiness and to the consequent effort
      in keeping attention focused on the tasks. The effects of DDS2700 on glucose
      metabolism at rest, and on rCBF during activation conditions, indicate a drug
      action on cerebral networks involved in alertness, vigilance and attention
      maintenance. PET assessment by [18F]FDG and water may provide complementary
      information in pharmacodynamic studies.

PMID- 11338051
TI  - Physical and biological dosimetry in patients undergoing radiosynoviorthesis with
      erbium-169 and rhenium-186.
AB  - Physical and biological dosimetry were investigated in 45 rheumatoid arthritis
      patients treated by radiosynoviorthesis (RSO) with 186Re-sulphide (medium-sized
      joints) and 169Er-citrate (digital joints). Biological dosimetry involved scoring
      dicentrics in lymphocytes, cultured from blood samples withdrawn just before and
      6 h, 24 h and 7 days after treatment. Physical methods included repeated blood
      sample counts and scintigraphy data. For erbium-169 (pure beta emitter), only
      bremsstrahlung could be measured and solely in the injection area. For rhenium
      186 (both beta and gamma emitter), whole body scans and static images of joints
      and locoregional lymph nodes were performed. Dosimetry calculations were in
      accordance with the MIRDOSE 3 software and tables. For erbium-169 (21 patients),
      either metacarpophalangeal (30 MBq) or proximal interphalangeal (20 MBq) joints
      of the hands were treated (one joint per patient); 18 patients (out of 21) were
      interpretable for biological dosimetry, 10 (out of 11) for physical dosimetry and
      six (out of 10) for both. For rhenium-186, 23 wrists, nine elbows, three
      shoulders and two ankles were injected in 24 patients, with a maximum of three
      joints per patient (70 MBq per joint); 20 patients (out of 24) and 10 (out of 10)
      were interpretable for biological and physical dosimetry, respectively, and eight
      (out of 10) for both methods. Erbium-169 biological dosimetry was negative in all
      interpretable patients, and physical dosimetry gave a blood dose of 15 +/- 29
      microGy and an effective dose lower than 1 mSv/30 MBq. For rhenium-186,
      biological results were negative in 16 patients (out of 20), but showed a blood
      irradiation around 200 mGy in the last four. A significant cumulative increase of
      dicentrics 7 days after injection (16/10,000 instead of 5/10,000 prior to
      treatment; p < 0.04) was also noted. Gamma counts gave a blood dose of 23.9 +/-
      19.8 mGy/70 MBq and the effective dose was found to be 26.7 +/- 5.1 mGy/70 MBq,
      i.e. about 380 microGy.MBq-1. Erbium-169 RSO is very safe from both physical and
      biological dosimetry standpoints. Rhenium-186 leak is greater, as demonstrated by
      the higher blood activity and the measurable, although limited, dicentrics
      induction in blood lymphocytes. However, the effective dose remains moderate,
      i.e. 30 times lower than in 131I therapy in benign thyroid diseases.

PMID- 11338052
TI  - 99Tcm-dimercaptosuccinic acid renal scintigraphy for detection of renal cortical
      defects in acute pyelonephritis: posterior 180 degrees SPECT versus planar image
      and 360 degrees SPECT.
AB  - To evaluate the usefulness of the posterior 180 degrees acquisition technique for
      renal defects in acute pyelonephritis (APN), a prospective study was conducted
      using planar imaging, 360 degrees and posterior 180 degrees renal single photon
      emission computed tomography (SPECT) with 99Tcm-dimercaptosuccinic acid. Sixty
      subjects with the suspicion of APN were included. The kidneys were divided into
      three zones: each was graded as positive, equivocal or negative for renal
      defects. To evaluate inter-observer variation, each study was read in a double
      blind fashion by two nuclear physicians. Renal defects were found in 24 patients
      (31 kidneys and 47 zones) with posterior 180 degrees SPECT, 23 patients (29
      kidneys and 44 zones) with 360 degrees SPECT (McNemar's test, P = 0.375 for
      zones) and 15 patients (16 kidneys and 24 zones) with planar image (P = 0.001 for
      zones, vs 180 degrees and 360 degrees SPECT). The proportion of positive
      agreement for posterior 180 degrees and 360 degrees SPECT between readers for the
      presence of renal defects was 0.81 and 0.62, respectively, whereas the proportion
      of negative agreement was 0.92 and 0.87, respectively. Both posterior 180 degrees
      and 360 degrees SPECTs significantly detected more renal defects than planar
      imaging. The detectability of renal defects in APN by posterior 180 degrees renal
      SPECT was equal to 360 degrees SPECT but inter-observer agreement was better.

PMID- 11338053
TI  - An assessment of perfusion deficits in decompression illness using 99Tcm HMPAO
      SPET and statistical parametric mapping.
AB  - AIM: The aim of this study was to use statistical parametric mapping (SPM) to
      investigate differences in the regional cerebral blood flow (rCBF) of
      decompression illness (DCI) and non-diving control subjects. METHODS: Twenty DCI
      subjects were imaged using 99Tcm hexamethylproplylene amine oxime (HMPAO) single
      photon emission tomography (SPET) within days of their incident of DCI, and on a
      second occasion between 2 and 27 months after their DCI event. SPM was used to
      make a comparison between decompression illness studies and a second group of non
      diving control studies for both early and late imaging of DCI. A paired
      comparison of early and late imaging was also performed testing for correlation
      between time of imaging and changes in the rCBF pattern. RESULTS: The comparison
      between control subjects and early imaging of decompression illness showed a
      large, significant (P = 0.002), irregularly shaped, multi-focal area of reduced
      uptake in the left occipito-parieto-temporal region of the brain. Comparisons
      between control and repeat decompression illness imaging studies showed two areas
      of reduced uptake. The first was similar to that found in the initial comparison
      although it was less significant (P = 0.035). The second region was similar but
      contra-lateral to the first region with significance P < 0.001. An attempt to
      correlate any changes in rCBF with the time that elapsed between each set of
      imaging found no areas of significant correlation. CONCLUSION: 99Tcm HMPAO SPET
      images of decompression illness display areas of reduced perfusion, which persist
      in the majority of cases.

PMID- 11338054
TI  - Influence of errors in sampling time and in activity measurement on the single
      sample clearance determination.
AB  - INTRODUCTION: Plasma clearance rate of 51Cr-EDTA estimated by using one blood
      sample is commonly used for the calculation of glomerular filtration rate. AIM:
      To estimate the error on single-sample clearance determination induced by errors
      in sampling time and activity measurement, and to compare it with the error
      observed on the clearance determination obtained using the slope-intercept
      method. METHODS: Forty-five adult patients were chosen from a data base of 51Cr
      EDTA plasma clearance values determined by using two blood samples taken around 2
      and 4 h. Patients were selected in such a way as to include clearances from 30
      ml.min-1 to 155 ml.min-1, with steps of 3 ml.min-1. Based on the slope and the
      intercept of the slope with the y-axis, the plasma concentration at exactly 2 and
      4 h was determined. Normally distributed random errors were then introduced in
      the sampling time (SD of 0, 1 and 2 min) as well as in the activity measurement
      (SD of 0, 1, 2 and 5%). Then, clearance was calculated using two single-sample
      methods (i.e. the algorithms of Groth and Tauxe), and the slope-intercept method,
      which requires two blood samples. For each setting, the simulation was repeated
      200 times. The effects on clearance of a random error on the time sampling and/or
      the activity measurement were then evaluated. RESULTS: The error on single-sample
      clearance induced by a 2 min error in sampling time associated with a 5% error in
      activity measurement was negligible. For all clearance levels, the SD of the
      error on the calculated clearance was less than 3.8 ml.min-1. Whatever algorithm
      was chosen, the errors on the single-sample clearance were systematically lower
      than those observed with the slope-intercept method, for the whole clearance
      range. CONCLUSION: Errors in sampling time and in activity measurement induced
      only a very small error on the single-sample EDTA clearance, which is
      systematically lower compared to that observed on the slope-intercept method
      using two blood samples.

PMID- 11338055
TI  - Pathogenesis of portal hypertension.
AB  - Portal hypertension is defined by an elevation in portal pressure and is
      associated with haemodynamic alterations. Haemodynamic changes are characterized
      by a hyperdynamic circulation in the splanchnic and systemic territories and a
      reduced pressure effect of vasoconstrictive substances. They were observed in
      both patients and animals with different types of portal hypertension. In this
      review, the main results and their mechanisms of the splanchnic and systemic
      haemodynamic alterations in portal hypertension are discussed.

PMID- 11338056
TI  - Ascites and hepatorenal syndrome.
AB  - Ascites is a frequent complication of chronic liver disease with severe portal
      hypertension. Moreover, in the presence of tense ascites, renal dysfunction and
      hepatorenal syndrome may occur. Unfortunately, there is no explanation that
      thoroughly describes the complex relationship between the liver and kidney in
      either physiological or pathological conditions. Nevertheless, available evidence
      indicates that early sodium and water retention precedes decompensation,
      characterized by hyperdynamic circulation. The best approach to the treatment of
      these patients should be aimed at the prevention of ascites formation. An
      accurate sequential treatment is indicated in patients with ascites. In the case
      of hepatorenal syndrome, the only definitive approach is liver transplantation.

PMID- 11338057
TI  - Hypersplenism.
AB  - Cytopenias in liver disease are a common finding. In the past they have mostly
      been attributed to pooling and/or destruction of blood cells in the enlarged
      spleen, leading to the term 'hypersplenism'. With recent advances in the
      understanding of the physiology of blood formation, in particular with the
      discovery of several haematopoietic growth factors, new insight into the
      pathophysiology of blood cell derangements in liver disease has been obtained.
      Recombinant haematopoietic growth factors present new opportunities for support
      of the haematopoietic system, which is required because of toxic antiviral
      therapies or surgical interventions in these patients.

PMID- 11338058
TI  - Hepatic encephalopathy.
AB  - In the last decade, a significant amount of research has been devoted to the
      pathogenesis and treatment of hepatic encephalopathy (HE). Non-invasive
      neuroimaging techniques such as magnetic resonance imaging and spectroscopy have
      become important research tools. The search for a suitable animal model of HE
      associated with cirrhosis is still ongoing. Moreover, consensus terminology and
      diagnostic criteria for HE in humans are badly needed.

PMID- 11338059
TI  - Management of acute variceal haemorrhage.
AB  - Endoscopic therapy and in particular endoscopic variceal banding ligation, in
      experienced hands, is the treatment of choice for acute variceal bleeding which
      remains a major cause of death in patients with cirrhosis and portal
      hypertension. Pharmacological therapy with Glypressin or somatostatin can be
      useful to gain time when the endoscopic expertise is not available or to help to
      obtain a clearer endoscopic view. Transjugular intrahepatic porto-systemic stent
      shunt is currently used for endoscopic failures, producing similar results with
      the surgical portacaval shunts. Which one of the two should be preferred, since
      they both work best in relatively compensated patients, should be a balance
      between the available surgical and radiological expertise, the urgency of the
      situation and the expected course of the disease.

PMID- 11338060
TI  - Prevention of rebleeding from oesophageal-gastric varices.
AB  - Endoscopic sclerotherapy or ligation and/or drugs are the standard treatments for
      the prevention of variceal rebleeding. Failure of this treatment indicates the
      need for rescue transjugular intrahepatic portosystemic shunt (TIPS)
      implantation. The current practice to use endoscopic treatment as first-line and
      TIPS as second-line treatment is, however, not based on evidence since, in
      unselected patients, both treatments have a comparable survival. In addition, the
      timing for a change from endoscopic treatment to TIPS is not exactly defined.
      According to the randomized studies available a change may be recommended when
      uncontrolled rebleeding or more than two rebleedings within a time interval of 6
      12 months indicate failure of the endoscopic treatment. This regimen may be
      reconsidered when future developments improve outcome of one or the other
      treatment. In this regard the TIPS treatment has a potential of improvement if
      further reduction of the rate of rebleeding can be achieved with less stenosis,
      and/or reduced encephalopathy.

PMID- 11338061
TI  - Primary prophylaxis of variceal bleeding in cirrhosis.
AB  - Variceal bleeding is the result of portal hypertension, which is a major
      complication of liver cirrhosis and carries a high mortality rate. Because of the
      mortality associated with variceal bleeding, strategies for prevention of the
      first bleed is important. Risk stratification is important in determining those
      at risk of bleeding from varices and current data suggest that patients with
      large varices with red signs, severe underlying liver disease and those who have
      a hepatic venous pressure gradient of greater than 12 mmHg are at high risk of
      bleeding. Surveillance for varices in patients with cirrhosis is therefore
      important. The current review evaluates the role of various treatments in the
      primary prophylaxis of variceal bleeding. The current first choice treatment is
      non-selective beta-blockers; which is cheap, easy to administer, and reduces the
      risk of first variceal haemorrhage significantly. Combination of beta-blockers
      and nitrates looks promising but needs further evaluation. Endoscopic variceal
      band ligation compares favourably with non-selective beta-blockers in preventing
      the first bleeding episode in cirrhotic patients and may be an alternative for
      patients who cannot tolerate, or have contraindications to beta-blockers. The
      role of monitoring the hepatic venous pressure gradient in those being treated
      with pharmacological agents, the role of newer drugs such as non-selective beta
      blockers with intrinsic alpha-adrenergic activity and angiotensin receptor
      blockers require further evaluation.

PMID- 11338062
TI  - Hepatitis B vaccination in liver transplant candidates.
AB  - Liver transplantation has become the treatment of choice for patients with end
      stage liver disease. De novo hepatitis B infection after liver transplantation is
      a rare event and usually runs a mild clinical and histological course. Despite
      the favourable outcome, a wide spectrum of hepatitis B virus (HBV)-associated
      liver disease may develop, ranging from asymptomatic carriage to severe chronic
      active hepatitis or cirrhosis and even fulminant hepatic failure. The achievement
      of protective titres of anti-HBs through vaccination has been suggested to be
      protective against the development of de novo HBV infection. The results of
      vaccination in cirrhotic patients awaiting for liver transplant have been very
      disappointing. High-dose/short-term schedules have been tried in transplant
      candidates in order to increase the response rate. New and more immunogenic
      formulations (containing new adjuvants or additional pre-S1/pre-S2 recombinant
      antigens), and, more importantly, early vaccination of potential transplant
      candidates at earlier stages of their liver disease should further prevent de
      novo hepatitis B in transplant recipients.

PMID- 11338063
TI  - Immunogenicity of two accelerated hepatitis B vaccination protocols in liver
      transplant candidates.
AB  - OBJECTIVE: It is common practice to immunize patients against hepatitis B virus
      infection prior to orthotopic liver transplantation (OLT). We compared the
      seroprotection rates of two accelerated schedules with a recombinant hepatitis B
      vaccine in patients awaiting OLT. DESIGN AND METHODS: Patients were prospectively
      recruited and vaccinated with either 20 micrograms (group 1, n = 14) or 40
      micrograms (group 2, n = 20) hepatitis B surface antigen per dosage. Thirty-nine
      healthy volunteers served as a historical control group. Patients in all groups
      were vaccinated with an accelerated schedule (0, 7 and 21 days). All patients
      underwent clinical and laboratory examinations (HBs antibodies, CD4/CD8 ratio,
      transaminases). RESULTS: The accelerated hepatitis B vaccination schedules were
      well tolerated. Eight weeks after the third injection, no significant differences
      in seroprotection rates were observed between group 1 (31%) and group 2 (26%).
      There was no correlation with respect to seroconversion rates and gender, smoking
      habits or CD4/CD8 ratio. CONCLUSION: These data suggest that accelerated
      vaccination schedules with a recombinant hepatitis B vaccine are safe and well
      tolerated, but only achieve poor seroconversion rates in OLT candidates.
      Increasing the vaccine dose to 40 micrograms hepatitis B surface antigen per
      injection did not result in a higher response rate. Because of the low risk of
      acquiring de novo hepatitis B infection after transplantation, it should be
      questioned whether routine hepatitis B vaccination with standard recombinant
      vaccines prior to liver transplantation should be recommended any longer.

PMID- 11338064
TI  - Transjugular intra-hepatic portosystemic shunt for refractory variceal bleeding.
AB  - BACKGROUND: The most dramatic complication of portal hypertension in cirrhotic
      patients is oesophageal variceal bleeding. Moreover, patients with bleeding
      unresponsive to medical and endoscopic treatment have a poor prognosis.
      OBJECTIVE: The aim of this study was to evaluate the efficacy of early
      transjugular intra-hepatic portosystemic shunt (TIPS) in patients with refractory
      variceal bleeding. PATIENTS AND METHODS: TIPS was performed for 28 patients (17
      were stage Child C), successfully in 26. Variceal bleeding was controlled in all
      but one successfully stented patient. RESULTS: There was no mortality associated
      with the procedure. The two patients with a failure of TIPS insertion died of
      persistent bleeding in the first 48 h after failed TIPS. The 40-day mortality
      rate was 25%. Five patients died (one from persistent bleeding from gastric
      varices and four from multi-organ failure). Using multivariate analysis, the only
      independent factor associated with early mortality was the total bilirubin value.
      Fifteen surviving patients were listed for liver transplantation: four deaths
      occurred, eight patients were transplanted in the 6 months after TIPS and three
      are still waiting. Among the six patients who survived but were ineligible for
      transplantation, two died and four are still alive. Two episodes of early
      rebleeding and eight of late rebleeding occurred. Actuarial survival was 75% at
      one year and 52% at two years. CONCLUSIONS: Early TIPS is an effective rescue
      therapy for controlling refractory variceal bleeding.

PMID- 11338065
TI  - Gastric corpus atrophy following eradication of Helicobacter pylori.
AB  - BACKGROUND: Atrophic gastritis can develop in patients with Helicobacter pylori
      infection leading to a reduction in basal acid output. Whether the atrophy that
      develops is reversible is controversial. OBJECTIVE: To investigate the effect of
      H. pylori eradication in infected subjects who had developed atrophy of the
      corpus mucosa. METHOD: Ten H. pylori positive patients with corpus atrophy were
      identified at oesophagogastroduodenoscopy (OGD). They received eradication
      therapy with amoxicillin, clarithromycin and omeprazole. Repeat OGD with biopsy
      was performed at least 3 months later. Fasting plasma gastrin was measured at
      baseline and at re-endoscopy. H. pylori eradication was confirmed by 13C urea
      breath testing. RESULTS: Median time to re-endoscopy was 5 months. There was
      improvement in corpus atrophy in 50% of patients after H. pylori eradication, and
      a significant reduction in plasma gastrin (P = 0.03). The index patients had a
      significant diminution of basal acid output compared to controls. CONCLUSION:
      Corpus atrophy as defined by the Sydney System is reversible in some patients
      after H. pylori eradication. Improvement in atrophy is associated with a fall in
      fasting plasma gastrin levels. This may have implications in the prevention of
      gastric carcinoma.

PMID- 11338066
TI  - The accuracy of the Helicobacter pylori stool antigen test in diagnosing H.
      pylori in treated and untreated patients.
AB  - OBJECTIVE AND DESIGN: To evaluate the performance of the Helicobacter pylori
      stool antigen test (HpSA test) in detecting H. pylori infection and monitoring
      the effect of treatment. This was done in two separate studies using either a
      biopsy or the 13C-urea breath test based 'gold standard' (in untreated and
      treated patients, respectively). SETTING: Endoscopy units of two general
      hospitals. PATIENTS: One hundred and twenty-eight dyspeptic patients undergoing
      endoscopy in the first study. Sixty-five patients receiving anti-H. pylori
      treatment in the second study. RESULTS: Sensitivity and specificity in untreated
      patients were 96.3% and 81.8%, respectively. Seven days after treatment, these
      figures were 20% and 95%, and 4 weeks after treatment they were 40% and 95%.
      CONCLUSION: The HpSA test is accurate in untreated patients but fails in
      monitoring treatment success.

PMID- 11338068
TI  - Results of a double-blind, randomized study to evaluate the efficacy and safety
      of Antibiophilus in patients with radiation-induced diarrhoea.
AB  - BACKGROUND AND AIMS: Gastrointestinal toxicity is frequently observed during
      radiotherapy for malignancies in the abdomen and pelvis. This study was performed
      to determine the efficacy and tolerability of Lactobacillus rhamnosus
      (Antibiophilus) in comparison to placebo in a double-blind trial design. Its aim
      was to determine any clinically relevant difference between Antibiophilus and
      placebo in terms of efficacy in patients suffering from mild to moderate
      diarrhoea induced by radiation therapy. METHODS: The study was performed in two
      radiotherapy units in Hungary; the results are based on the data for 206
      recruited patients. RESULTS: Based on statistical analysis, Antibiophilus
      patients showed superiority with respect to the number of bowel movements (P <
      0.10) and faeces consistency ratings by the investigators (P < 0.05) at the study
      end. Statistical analysis of the patients' self-ratings with regard to diarrhoea
      grade and faeces consistency showed a statistically highly significant treatment
      by-time interaction (P < 0.001) which was supported by the evidence of tendencies
      or P values below the nominal 5% level in the second half of this study.
      CONCLUSIONS: Overall, there was a highly favourable benefit/risk ratio in favour
      of Antibiophilus.

PMID- 11338067
TI  - CLO vs histology: optimal numbers and site of gastric biopsies to diagnose
      Helicobacter pylori.
AB  - OBJECTIVE: To determine the optimal numbers and sites of biopsies required for
      diagnosis of Helicobacter pylori by using the CLOtest and comparing the results
      with those of a routine histological assessment in a district general hospital
      (DGH) setting. METHODS: A prospective study comparing the sensitivity of the
      CLOtest containing one antral (CLO 1), two antral (CLO 2) and two antral and one
      body biopsy (CLO 3), and with histological examination for H. pylori. Consecutive
      patients undergoing upper gastrointestinal endoscopy (UGIE) at Stepping Hill
      Hospital, Stockport, UK, who had evidence of gastritis, gastric ulcer, duodenitis
      or duodenal ulcer were included in the study. RESULTS: Ninety-six patients were
      biopsied. Forty were positive on at least one of the CLOtests; of these, nine
      were negative on histological assessment. Of these nine, two were positive on all
      CLOtests and seven were positive only on CLO 3. One was positive on histology but
      negative on all CLOtests. This study showed that CLO 3 was more sensitive than
      CLO 1 (P = 0.004), CLO 2 (P = 0.016) and histology (P = 0.022). There was no
      significant difference between CLO 1 and CLO 2 (P = 0.500), CLO 1 and histology
      (P = 1.000), CLO 2 and histology (P = 1.00). CONCLUSION: We feel that in a busy
      clinical setting, taking two antral and one body biopsy in a single CLOtest is
      superior to routine histological assessment for the detection of H. pylori, with
      resulting cost saving.

PMID- 11338069
TI  - Ridogrel enemas in distal ulcerative colitis.
AB  - OBJECTIVE: To evaluate the effect of Ridogrel enemas (Janssen Research
      Foundation, Beerse, Belgium) on disease activity and mucosal inflammatory
      mediators in patients with active left-sided ulcerative colitis. DESIGN AND
      METHODS: Eleven patients with active left-sided ulcerative colitis were evaluated
      in an open non-placebo-controlled pilot study. All patients were treated with
      Ridogrel enemas (300 mg/40 ml once daily) over four weeks. A disease activity
      score based on clinical, endoscopic and histological criteria was obtained before
      and after treatment with Ridogrel. The concentrations of thromboxane B2 (TxB2),
      prostaglandin E2 (PGE2), interleukin-6 (IL-6) and tumour necrosis factor alpha
      (TNF-alpha) were measured in mucosal biopsies before and after treatment.
      RESULTS: One patient discontinued treatment because of progression of disease,
      the other ten patients tolerated the Ridogrel enemas well. Mucosal TxB2
      concentration decreased significantly in all patients. The mucosal concentrations
      of the other inflammatory mediators (PGE2, IL-6 and TNF-alpha) were unaltered.
      The disease score decreased in five patients. However, clinical improvement was
      not always associated with a decrease in endoscopic and/or histological scores.
      CONCLUSIONS: This pilot study shows that Ridogrel enemas selectively reduce
      mucosal TxB2 concentration.

PMID- 11338070
TI  - Stressful life events and recurrent abdominal pain in children in a rural
      district in Malaysia.
AB  - OBJECTIVE: The purpose of this study was to look at the correlation between
      recurrent abdominal pain and the presence of recent stressful life events among
      schoolchildren in a rural district in Malaysia. METHOD: This is a cross-sectional
      study of schoolchildren aged 9-15 years based in Kuala Langat, a rural district
      located in the south-west of the Malaysian state of Selangor. Schoolchildren were
      selected randomly and given questionnaires to fill in. This was followed by
      interview with the children on the same day by one of the authors (CCMB) to
      ensure consistency of response. Recurrent abdominal pain was defined as 'at least
      three episodes of abdominal pain, severe enough to affect their activities over a
      period longer than three months' [1]. The children were also asked to answer
      either 'yes' or 'no' to whether they had experienced various life events in the
      previous year. RESULTS: A sample of 1462 schoolchildren (722 boys and 740 girls)
      aged between 9 and 15 years were included in the study. There were 768 Malays,
      393 Chinese and 301 Indians. Of these 1462 children, 161 (11.0%) had recurrent
      abdominal pain. On performing multiple logistic regression analysis, two life
      events were significantly associated with recurrent abdominal pain: death of a
      family member (P = 0.008; odds ratio 0.61, 95% CI 0.43-0.88) and a change in
      occupation of an immediate family member (P = 0.003; odds ratio 0.53, 95% CI 0.35
      0.81). CONCLUSION: This study suggests that recurrent abdominal pain in children
      is associated with recent stressful life events in the children's lives.

PMID- 11338071
TI  - Neuroendocrine differentiation is a relevant prognostic factor in stage III-IV
      colorectal cancer.
AB  - OBJECTIVE: To determine the prognostic relevance of neuroendocrine
      differentiation in colorectal cancer. METHODS: The survival of 116 patients with
      colorectal cancer of stages III (n = 59) and IV (n = 57) was correlated with the
      extent of neuroendocrine differentiation. Chromogranin A and synaptophysin were
      used as neuroendocrine markers. Based on the degree of immunoreactivity for these
      markers, tumours were classified as 0 (no expression of neuroendocrine markers),
      1 (< 2% cells staining positive for neuroendocrine markers) and 2 (> 2% cells
      staining positive for neuroendocrine markers). Patients were followed up for more
      than 5 years or until death. RESULTS: Seven of 59 (11.8%) stage III cancers and
      13/57 (22.8%) stage IV cancers belonged to group 2. The 96 patients of groups 0
      and 1 lived for 48.9 months, whereas the 20 patients of group 2 survived for only
      18.6 months (Kaplan-Meier survival curves, P < 0.001). The difference was most
      striking in stage III disease with 79.4 months' survival for combined groups 0
      and 1, and 38.9 months' survival for group 2 (P < 0.01). Using the multivariate
      Cox regression model, the presence of more than 2% of cells with neuroendocrine
      differentiation was found to be an independent prognostic parameter for stage III
      and IV disease. No correlation was observed between neuroendocrine
      differentiation and tumour location, grade, depth of invasion or stage.
      CONCLUSION: Neuroendocrine differentiation is often seen in colorectal cancer. It
      is an independent prognostic factor in stage III-IV colorectal cancer.

PMID- 11338072
TI  - Rectal inhibition by inferior rectal nerve stimulation in dogs: recognition of a
      new reflex--the 'voluntary anorectal inhibition reflex'.
AB  - OBJECTIVE: The effect of inferior rectal nerve (IRN) stimulation on the rectum
      was studied, postulating that nerve stimulation might inhibit rectal
      contractility and could thus be used in the management of defecation disorders.
      METHOD: The IRN was exposed through a para-anal incision in 12 dogs (18.2 +/- 3.3
      SD kg, seven male, five female) and a cuff-type electrode was applied to the
      nerve. A balloon introduced into the rectum was filled with saline in increments
      of 5 ml. The rectal and rectal neck (anal canal) pressures, and the
      electromyographic (EMG) activity of the external anal sphincter (EAS) and
      Internal anal sphincter (IAS) were recorded until the balloon was expelled to the
      exterior. The test was repeated until the expulsion volume was reached, and the
      IRN was stimulated (pulse width 200 mu/s, charge density 2 to 6 microCi/cm2 per
      phase). The test was performed again following individual anaesthetization of the
      EAS and the IAS. RESULTS: At a mean rectal distending volume of 38.3 +/- 2.3 ml,
      the rectal pressure increased (P < 0.01), rectal neck pressure declined (P <
      0.01), the EAS and IAS EMGs disappeared, and the balloon was expelled. IRN
      stimulation at a distending volume of 38.3 +/- 2.3 ml increased the EMG activity
      of the EAS, whereas the rectal pressure and IAS EMG did not change (P > 0.05) and
      the balloon was not expelled. With IRN stimulation at the distending volume of
      38.3 +/- 2.3 ml while the EAS was anaesthetized, the rectal pressure increased (P
      < 0.01), rectal neck pressure diminished, IAS EMG activity disappeared, and the
      balloon was expelled. Upon repetition of IRN stimulation during anaesthetization
      of the IAS, the rectal pressure remained high and the balloon was not expelled.
      CONCLUSION: It is suggested that the EAS produces continence by a twofold action.
      The EAS prevents IAS relaxation on rectal contraction, with a resulting rectal
      relaxation. A reflex relationship is postulated to exist between failure of the
      IAS to relax and rectal relaxation. We call this reflex relationship 'voluntary
      anorectal inhibition reflex'. Secondly, the EAS mechanically compresses the
      rectal neck. It seems that contraction of the EAS, which is a striated muscle,
      mechanically occludes the rectal neck for a few seconds--enough for the rectum to
      relax in a reflex manner as an effect of the voluntary anorectal inhibition
      reflex.

PMID- 11338073
TI  - Bone mineral content and density in asymptomatic children with coeliac disease on
      a gluten-free diet.
AB  - OBJECTIVES: Osteoporosis is a complication of coeliac disease. A gluten-free diet
      improves but does not normalize bone mineral density in adult patients. Only
      limited data are available regarding the influence of the disease and diet on
      bone mineralization in children. The aim of this study was to evaluate the radial
      bone mineral content and density in children and adolescents who are asymptomatic
      on a gluten-free diet. SUBJECTS AND METHODS: The bone mineral content (BMC) and
      density (BMD) values of the non-dominant radius midshaft in 91 children (53
      girls, 38 boys, mean age 11.7 years, mean duration of disease 8.7 years) were
      determined by single-photon absorptiometry. At the diagnosis and at least three
      years after commencement of a gluten-free diet, serum calcium, phosphorus,
      albumin concentrations and alkaline phosphatase activities were measured in all
      patients, and intact parathormone concentrations in 16 patients. RESULTS: The
      mean BMC Z-score value in the female adolescent group only was significantly
      lower than normal (mean Z-score -1.04, P < 0.01). In contrast, the mean BMD Z
      score was significantly higher compared to a healthy population both in girls
      (mean Z-score +1.36, P < 0.001) and in boys (mean Z-score +0.53, P < 0.02), as
      well as in the total patient group (mean Z-score +1.01, P < 0.001). The radial
      diameter was significantly smaller than normal in both pre-pubertal and
      adolescent groups. Serum laboratory parameters of asymptomatic patients were in
      the normal range. The parathormone mean value was significantly lower after at
      least three years of gluten-free diet than at diagnosis (mean +/- SD 3.77 +/-
      1.07 versus 7.89 +/- 2.54 pmol/l, P < 0.01), but significantly higher compared to
      controls (2.89 +/- 0.90 pmol/l, P < 0.05). CONCLUSIONS: These data indicate that
      treated, asymptomatic coeliac children and adolescents have normal or even higher
      radius mineral density values than controls, but the bone size remains reduced.
      Although there is no direct evidence of calcium malabsorption in this cohort of
      coeliac patients, the slightly higher parathormone levels, together with some
      other factors, particularly delayed puberty, may result in reduced bone size.

PMID- 11338074
TI  - Eosinophilic gastroenteritis treated with non-enteric-coated budesonide tablets.
AB  - A patient who presented with upper abdominal pain, nausea and ascites together
      with peripheral eosinophilia is described. Based on a surgical full-thickness
      biopsy of the antrum, the diagnosis of eosinophilic gastroenteritis was made.
      Treatment with prednisone resulted in a clinical response, but the prednisone
      dose could not be lowered below 5 mg. We preferred to treat the patient with
      corticosteroids with minimal systemic side effects. As there was gastric
      involvement, we could not give enteric-coated budesonide capsules. Therefore, we
      treated the patient with budesonide tablets, which were designed originally for
      use as a clysma but now are given orally. With this treatment regimen, the
      patient has been in remission for more than 2 years.

PMID- 11338075
TI  - Necrotizing fasciitis in Crohn's disease.
AB  - We report a case of a 34-year-old woman, presenting initially with anaemia
      followed by sacro-iliac pain, and subsequently found to have necrotizing
      fasciitis complicating Crohn's disease where the organisms were introduced via a
      fistulous tract. It is perhaps surprising that this is not a more common
      complication of fistulating Crohn's disease, but we believe this is the first
      case report of this particular complication.

PMID- 11338076
TI  - Genotype-phenotype interactions in Wilson's disease: insight from an Icelandic
      mutation.
AB  - Wilson's disease, an autosomal recessive disorder of copper transport, usually
      presents with symptoms from the liver or central nervous system. Rarely, the
      initial manifestation is fulminant hepatic failure. The abnormal gene (ATP7B) is
      located on chromosome 13q and encodes a copper-transporting ATPase. A large
      number of mutations have been reported. We describe a previously healthy 16-year
      old girl who presented with fulminant hepatic failure. The girl died within 24 h
      of admission to a hospital from refractory shock. Autopsy revealed cirrhosis and
      widespread necrosis of the liver. The copper content of the liver was markedly
      increased (975 micrograms/g dry weight), strongly suggesting a diagnosis of
      Wilson's disease. Genetic studies revealed that the girl was homozygous for the
      mutation 2007 del7, which is the mutation found in all Wilson's disease patients
      previously identified in Iceland. This is the first known case of fulminant
      hepatic failure due to Wilson's disease in Iceland. Despite the same mutation,
      the clinical picture is vastly different from other Icelandic patients with
      Wilson's disease, who all presented with relatively late-onset neurological
      disease. This suggests that factors other than the specific mutation have
      significant impact on the phenotype of the disease.

PMID- 11338077
TI  - Tuberculous liver abscess: a case report and review of literature.
AB  - Tuberculous liver abscess is rare worldwide. We report a 45-year-old man who
      presented with abdominal pain, fever and weight loss. Ultrasound and computed
      tomography of the abdomen showed multiple cystic lesions in the liver. Ultrasound
      guided needle aspiration revealed yellowish brownish aspirate, which was flooded
      with acid-fast bacilli. The abscess was drained under ultrasound guidance.
      Subsequent abdominal ultrasound a few days later showed resolution of the abscess
      cavity. He was concomitantly started on systemic antituberculous therapy. A
      tuberculous liver abscess has to be thought of in the differential diagnosis of
      liver abscesses and to consider the role of percutaneous drainage along with
      systemic antituberculous chemotherapy as an alternative to surgery in the
      management. A greater awareness of this clinical entity is required for
      successful treatment.

PMID- 11338078
TI  - Pathophysiology and management of bowel dysfunction in multiple sclerosis.
AB  - The prevalence of bowel dysfunction in multiple sclerosis (MS) patients is higher
      than in the general population. Up to 70% of patients complain of constipation or
      faecal incontinence, which may also coexist. This overlap can relate to
      neurological disease affecting both the bowel and the pelvic floor muscles, or to
      treatments given. Bowel dysfunction is a source of considerable ongoing
      psychosocial disability in many patients with MS. Symptoms related to the bladder
      and the bowel are rated by patients as the third most important, limiting their
      ability to work, after spasticity and incoordination. Bowel management in
      patients with MS is currently empirical. Although general recommendations include
      maintaining a high fibre diet, high fluid intake, regular bowel routine, and the
      use of enemas or laxatives, the evidence to support the efficacy of these
      recommendations is scant. This review will examine the current state of knowledge
      regarding the pathophysiological mechanisms underlying bowel dysfunction in MS,
      outline the importance of proper clinical assessment of constipation and faecal
      incontinence during the diagnostic work-up, and propose various management
      possibilities. In the absence of clinical trial data on bowel management in MS,
      these should be considered as a consensus on clinical practice from a team
      specialized in bowel dysfunction.

PMID- 11338079
TI  - Heparin therapy for ulcerative colitis? Effects and mechanisms.
AB  - Despite intensive medical treatment with steroids and immunosuppressants, acute
      colitis is still associated with a colectomy rate of up to 15%. Following the
      observation that a patient with severe steroid-resistant colitis went into
      remission when treated with heparin for a deep vein thrombosis, there have been a
      number of reports on the use of heparin in acute ulcerative colitis. Although
      small and uncontrolled, these studies consistently demonstrate the beneficial
      effects of heparin, with surprisingly few side-effects in a disease characterized
      by mucosal haemorrhage. The mechanisms by which heparin may ameliorate ulcerative
      colitis remain unclear. A simple anticoagulant effect may be responsible, but
      similar effects are not seen with warfarin. As a result of their intense negative
      charge, the glycosaminoglycans that constitute heparin have diverse biological
      effects. These include potent anti-inflammatory actions, in vitro and in vivo,
      and the potentiation of the activity of the peptide growth factors necessary for
      mucosal regeneration and repair. This review summarizes the clinical reports on
      heparin treatment for ulcerative colitis and explores the mechanisms by which
      this novel form of treatment may exert its effects.

PMID- 11338080
TI  - Azathioprine as a treatment of refractory lymphocytic colitis.

PMID- 11338081
TI  - The FDA's enforcement of age restrictions on the sale of cigarettes and smokeless
      tobacco.
AB  - The nation's largest tobacco age-restriction enforcement program is described.
      Between 1997 and 2000, the U.S. Food and Drug Administration--working with state
      agencies--conducted nearly 200,000 compliance checks in 123,000 establishments in
      44 states, 1 territory, and Washington, D.C. The overall violation rate was 26
      percent (more than 40,000 violations), ranging from 9 percent in Maine to 54
      percent in the Virgin Islands. Due to the recent Supreme Court ruling, the FDA
      has stopped conducting these checks and is shutting down its tobacco program. The
      protocol described in this article will prove useful to others conducting
      compliance checks and seeking to keep tobacco out of the hands of children.

PMID- 11338082
TI  - Age-appropriate HIV prevention messages for older adults: findings from focus
      groups in New York State.
AB  - The Emerging Issues Committee of the New York State HIV Prevention Planning Group
      identified that prevention messages were not including persons 50 and older and
      that 15 percent of the newly reported AIDS cases in 1997 in New York were in this
      age group. Recognizing that there may be unique needs in targeting prevention
      messages for this age group, a consultant conducted five focus groups throughout
      the state to speak with people to determine what they identified as unique themes
      related to HIV prevention for this age group.

PMID- 11338083
TI  - The formation of a complex community program for diabetes control: lessons
      learned from a case study of Project DIRECT.
AB  - A case study was conducted of the formation of a diabetes initiative in a largely
      African American urban community. The study focused on how confluent the original
      project model was with actual formation, what benefits were produced, what areas
      of needed improvement surfaced, and how different stakeholder groups
      characterized one another's involvement. The project produced several benefits
      but also experienced needed improvements in its formation, which suffered from a
      lack of communication, cooperation, and coordination; unclear goals and personnel
      roles; and early delays. Lessons include treating project formation as an
      important developmental stage and reducing bureaucratic management approaches not
      suited for community partnerships.

PMID- 11338084
TI  - Racial and ethnic disparities in infant mortality: risk in social context.
AB  - This article presents the multifaceted efforts of Syracuse Healthy Start, a
      federally funded initiative of the Onondaga County Health Department and over 20
      partnering agencies to reduce racial and ethnic disparities in infant mortality.
      The analyses presented in this article demonstrate that many women--Caucasian,
      African American, and Hispanic--have serious risks for low birth weight and
      infant death. In many cases, multiple, simultaneous risks complicate a pregnant
      woman's situation and in other cases the longitudinal cumulative risks impact
      health across generations. Infant mortality decreased overall, and for both
      Caucasian and African American infants during the first 3 years of the project.

PMID- 11338085
TI  - Benchmarking applications: linking state strategic planning, quality improvement,
      and consumer reporting.
AB  - This article demonstrates the value of using benchmark patient satisfaction data
      for Medicaid program quality improvement. The authors compare surveys of Maryland
      Medicaid and federal employees in Maryland, utilizing the latter as an external
      benchmark. Unadjusted and adjusted analyses found a significantly lower
      percentage of Medicaid than federal respondents rated telephone access excellent,
      very good, or good, whereas more Medicaid respondents rated advice on prevention
      and choice of primary care doctor highly. Patient satisfaction external benchmark
      data provide managed care organizations (MCOs) and state policy makers with goals
      to improve quality and standards to measure care objectively in vulnerable
      populations.

PMID- 11338086
TI  - Halting the illegal sale of prescription medications in Los Angeles County.
AB  - The illegal sale of prescription medications by unlicensed vendors is a
      widespread practice in Los Angeles County. Many members of ethnic and
      particularly Latino communities turn to unlicensed vendors because of financial
      and cultural reasons and/or a lack of access to the U.S. health care system. In
      response, Los Angeles County Department of Health Services developed a two-part
      effort to curb the illegal sale of pharmaceuticals. Dramatically increased law
      enforcement resulted in 280 investigations, 121 arrests, and the confiscation of
      $4-$4.5 million worth of illegal pharmaceuticals during the first 20 months. The
      department also has begun outreach efforts to educate those communities most
      affected by these practices.

PMID- 11338087
TI  - Comparison of vaccine coverage levels from the National Immunization Survey and
      the Texas Retrospective Immunization Survey.
AB  - The purpose of this study was to compare National Immunization Survey (NIS)
      vaccine coverage rates with Texas Retrospective Immunization Survey (TRIS)
      vaccine coverage levels. Up-to-date rates for children 19 through 35 months of
      age as of October 1, 1994, were calculated for single vaccines and two vaccine
      combinations. The TRIS weighted statewide up-to-date rates for 4-3-1 and 4-3-1-3
      were 66 percent and 60 percent, respectively, versus 71 percent and 68 percent
      for the NIS. Existing retrospective survey procedures can be modified to produce
      results that may be compared with the NIS.

PMID- 11338088
TI  - Mumps surveillance: results of improved case investigation and serologic testing
      of suspected cases, Texas, 1995-1996.
AB  - Mumps, one of several once common childhood diseases, is targeted for elimination
      in the United States by 2010. To improve its ability to monitor mumps cases, the
      Texas Department of Health began requiring investigation and serologic testing of
      all mumps reports. During 1995-1996, of 500 mumps reports, only 14.4 percent were
      confirmed cases and they had a different demographic profile than unconfirmed
      cases. To accurately assess whether the nation achieves the Year 2010 mumps
      elimination goal, and to effectively direct elimination efforts, states must
      investigate and serologically confirm all mumps reports and use the case
      definition for public health surveillance.

PMID- 11338089
TI  - Population-based health principles in medical and public health practice.
AB  - Traditionally, medical education, research, and practice have focused on the care
      of the individual but an increasing emphasis on the care of populations has
      raised awareness among academic medical centers, integrated delivery systems, and
      managed care organizations of the value of embracing population-based health
      principles. Five principles are relevant in this regard: a community perspective,
      a clinical epidemiology perspective, evidence-based practice, an emphasis on
      outcomes, and an emphasis on prevention. This article describes these
      interrelated concepts together with specific strategies to effect implementation.
      Widespread awareness and adoption of these principles will have a profound impact
      on medical and public health education, practice, and ultimately the public's
      health.

PMID- 11338090
TI  - Ensuring public health professionals go the distance: a case study from an online
      data skills course.
AB  - Distance learning methodologies provide an effective and economical means for
      professional staff to advance their skills while continuing to meet their
      extensive work-related responsibilities. However, motivating professionals to
      engage in training opportunities that do not include the customary features of a
      trip out of town and time away from the office is a challenge for distance
      training initiatives aimed at the public health workforce. This article describes
      the implementation of several features designed to motivate public health
      professionals to participate in an online analytic skills course.

PMID- 11338091
TI  - Public health case studies: a new MPH requirement bridging academia and practice.

PMID- 11338092
TI  - Missing in action: the public health voice in policy debates.

PMID- 11338093
TI  - Ensuring that public health "practice" makes perfect.

PMID- 11338094
TI  - Clinical governance: risks and quality control in radiotherapy.
AB  - The professions involved in radiotherapy constantly strive to improve quality and
      to minimize errors and their effects. We are aware of our shortcomings but
      sometimes are powerless to take corrective action. We have seen that clinical
      governance requires some change in the medical culture but much has yet to be
      achieved in the standardization of medical processes. We would gain by sharing
      experiences of system failures, whether that be by reporting near misses or by
      disseminating details of litigation cases. In a specialty that depends on human
      processes and interactions, it is no surprise to find a measurable incidence of
      human errors. Sometimes this is also related to technological or design
      deficiencies and we rely too much on human interventions to overcome these. We
      would like to take positive steps to improve quality, such as those inherent in
      the new ISO9000 standards, but we are hindered by a variety of constraints-
      manpower, old technology, pressure to achieve high patient throughput. We need to
      make decisions for the future development of radiotherapy in the UK. We could
      settle for a system that is characterized by high throughput and high risk.
      Hopefully, we will receive the necessary encouragement and resources to strive
      for high standards of treatment and low risk.

PMID- 11338095
TI  - Increasing the diagnostic yield of renal angiography for the diagnosis of
      atheromatous renovascular disease.
AB  - Atheromatous renovascular disease (ARVD) is a common cause of hypertension and
      chronic renal failure (CRF). In this unit, intravenous digital subtraction
      angiography (DSA) (or intraarterial DSA if indicated) is used as a screening
      angiographic study when ARVD is suspected. However, increased use of these
      investigations has resulted in a longer waiting time for angiography. As the
      majority of studies are negative for ARVD, clinical features and results of
      investigations of patients undergoing angiography were reviewed to identify those
      having the greatest likelihood of ARVD. The clinical notes were reviewed for all
      249 patients undergoing angiography over an 18-month period. Primary indications
      for investigation were: hypertension 71 (28.5%), CRF 156 (62.7%) and CRF with
      severe hypertension 22 (8.8%). 12 of the CRF patients had end-stage renal
      failure. 166 (66.7%) patients had no evidence of ARVD, while only 83 (33.3%)
      patients showed some degree of ARVD, 29 (35%) of which had bilateral renal artery
      disease. There was no significant difference between the ARVD group and the non
      ARVD group for mean age (69.0 years vs 63.3 years), male to female ratio, history
      of smoking (68.7% vs 55.4%), severe hypertension (10.8% vs 9.0%),
      hypercholesterolaemia (61.4% vs 47.0%), diabetes mellitus (28.6% vs 25.3%) or
      angiotensin converting enzyme inhibitor-related renal dysfunction (9.6% vs 6.1%).
      More patients in the ARVD group were investigated for CRF than in the non-ARVD
      group, as reflected by the higher serum creatinine level and the lower creatinine
      clearance in the ARVD group. 55 (33.1%) of the non-ARVD patients had no comorbid
      vascular disease, vascular bruits or ultrasound discrepancy in the size of the
      two kidneys, whereas all ARVD patients had at least one of these features
      (negative predictive value 100%). All three features were present in 19.3% of
      ARVD patients but in only 3.0% of the non-ARVD patients (positive predictive
      value 76.2%, specificity 97%). We plan to rationalize the criteria for
      angiography in the light of these findings, anticipating an increase in the
      diagnostic yield of renal angiography from its current 33.3% to above 42%.

PMID- 11338096
TI  - Comparison of CT angiography with conventional arterial angiography in aortoiliac
      occlusive disease.
AB  - This study compared the results of conventional and CT angiography of the
      aortoiliac segment in 35 patients with occlusive disease. Disease severity was
      graded into five categories. Two assessors independently assessed the segment
      from the distal abdominal aorta to the proximal superficial femoral artery and a
      consensus was formed. There was interobserver agreement in 87% of segments for
      conventional angiography and in 78% for CT angiography. Comparison of the two
      modalities gave identical grading in 84% of segments. Dissimilar grading was
      found in 16%, with a roughly equal number of undergrading and overgrading. CT
      angiography has the advantages of being minimally invasive, requiring only an
      intravenous injection of contrast medium and imaging surrounding soft tissues.
      Multiplanar reconstruction aids the visualization of asymmetrical stenoses, and
      collateral blood supply is readily appreciated. However, CT angiography may fail
      to demonstrate short stenoses owing to limited z-axis resolution.

PMID- 11338097
TI  - MRI of primary non-Hodgkin's lymphoma of the palatine tonsil.
AB  - Non-Hodgkin's lymphoma (NHL) arising primarily in the palatine tonsil is
      uncommon. The aims of the study were to describe the appearances on MRI and to
      identify the features that help to distinguish NHL from other tonsillar tumours.
      The clinical records and MR images of eight patients with primary NHL of the
      palatine tonsil were reviewed. Patients had a short duration of symptoms (mean 1
      month). Systemic symptoms (fever, weight loss or night sweats) occurred in two
      patients. Tumours were round or lobulated and ranged in size from 30 mm to 70 mm.
      The signal intensity on T2 weighted, T1 weighted and T1 weighted contrast
      enhanced images was homogeneous and similar to that of normal tonsil in six
      patients. Two large tumours were mildly heterogeneous and one of these showed
      small foci of necrosis. NHL of the tonsil displaced rather than invaded local
      structures in seven patients and locally invaded the soft palate in only one
      patient. Lymphadenopathy was present in five patients and the nodes were of
      similar signal intensity to the primary tumour. There was involvement of the
      ipsilateral upper internal jugular chain in all cases of lymphadenopathy. The
      posterior triangle was involved in two patients, the periparotid node in one
      patient and the retro-oropharyngeal region in one patient. The presence of a
      large tumour without deep invasion together with homogeneous non-necrotic nodes
      suggests the diagnosis of NHL. As NHL frequently has similar signal intensity to
      normal tonsil, MRI may not be able to detect lymphomatous involvement in the non
      enlarged tonsil.

PMID- 11338098
TI  - The role of preliminary interpretation of chest radiographs by radiographers in
      the management of acute medical problems within a cardiothoracic centre.
AB  - Radiographic staff in a regional cardiothoracic centre were asked to assess all
      pre- and post-operative chest radiographs over a 6-month period. Radiographs
      showing new, acute changes were noted and a red dot placed on the film. Medical
      staff were notified of radiographs with red dots, and these were subsequently
      reported by radiologists. Using reports by radiologists as the gold standard, an
      audit was performed of the radiographers' accuracy in identifying new
      abnormalities. The absence of a necessary red dot as well as inappropriate use
      were noted. To enhance the accuracy of radiograph interpretation, a series of
      lectures on the chest radiograph and a protocol for red dot use were developed by
      senior radiologists. During this 6-month period 8614 chest radiographs were
      taken; red dots were applied to 464 (5%). These red dots were considered
      incorrect in 100 radiographs. Radiographers misinterpreted or missed potentially
      important changes in 38 of the remaining 8150 radiographs without red dots
      (sensitivity and specificity of 90% and 99%, respectively). Radiographers
      appeared to err on the side of caution when confronted with an abnormal chest
      radiograph, especially when previous radiographs and reports were unavailable.
      This resulted is a relatively high false positive rate. Future audits will show
      whether this rate can be reduced by continued training. Subtle interpretation is
      crucial to distinguish between an abnormal chest radiograph needing urgent
      medical attention and an abnormal chest radiograph with normal post-operative
      changes. The opinion of the experienced and trained radiographer is immediate and
      may be invaluable to the diagnostic care of the patient.

PMID- 11338099
TI  - Mathematical segmentation of grey matter, white matter and cerebral spinal fluid
      from MR image pairs.
AB  - The aims of this study were (1) to design a mathematical segmentation technique
      to allow extraction of grey matter, white matter and cerebral spinal fluid
      volumes from paired high resolution MR images and (2) to document the statistical
      accuracy of the method with different image combinations. A series of linear
      equations were derived that describe proportional tissue volumes in individual
      image voxels. The equations use estimates of pure tissue values to derive the
      proportion of each tissue within a single voxel. Repeatability of manual
      estimations of pure tissue values was assessed both using regions of interest and
      thresholding techniques. Statistical accuracy of tissue estimations for a variety
      of image pairs was assessed from measurements of root-mean-square noise and mean
      grey level intensity. The technique was used to produce parametric images of grey
      and white matter distribution. The segmentation technique showed greatest
      statistical accuracy when the first image has high grey/white matter contrast and
      the second image has little contrast or the rank order of the signal intensities
      from pure tissue is reversed. A combination of inversion recovery fast spin echo
      and fast FLAIR images produced a statistical error of 11% for grey matter and 10%
      for white matter for any given voxel. The effect of increasing sample size
      improves both of these figures to give a 1% statistical error on a 100 pixel
      sample.

PMID- 11338100
TI  - Image segmentation in treatment planning for prostate cancer using the region
      growing technique.
AB  - The purpose of this study was to evaluate the performance of a region growing
      technique for segmenting prostate, bladder and rectum in CT images of prostate
      cancer patients. Prostate, bladder and rectum were segmented in all CT images of
      10 patients using the region growing technique and manual tracing. Volumes of the
      above organs computed with the region growing technique were compared with those
      from manually traced images on a slice-by-slice basis. Measurement
      reproducibility of both segmentation techniques was evaluated using the data
      obtained from four independent observers. The region growing technique was 1.5
      times faster than manual tracing. There was no statistical difference between the
      slice volumes of prostate, bladder and rectum obtained by the two segmentation
      techniques (p > 0.05, paired Student's t-test). Correlation between slice volumes
      of all organs of interest provided both by region growing and by manual tracing
      was very good (prostate r2 = 0.84; bladder r2 = 0.93; rectum r2 = 0.85). An
      overall reasonable agreement was found between the two segmentation techniques.
      The intraobserver and interobserver variations for prostate, bladder and rectum
      volume segmentation were found to be lower with the region growing technique than
      with manual tracing. The suggested semi-automatic technique allows the
      possibility of generating accurate and reproducible segmentation of prostate,
      bladder and rectum from CT data with great saving in labour.

PMID- 11338101
TI  - Influence of a vac-fix immobilization device on the accuracy of patient
      positioning during routine breast radiotherapy.
AB  - Continued use of basic planning and treatment techniques, in contrast to the
      improved methods implemented at many other anatomical sites, has emphasized the
      need for improved breast dosimetry. Any future technique delivering a superior
      three-dimensional dose distribution will be of maximum benefit if set-up errors
      are minimized. To determine the influence of vacuum moulded bag (vac-fix)
      immobilization on routine breast radiotherapy, 17 patients received half their
      radiotherapy fractions using our standard breast board technique and half using a
      vac-fix device positioned on the breast board. Treatment accuracy and
      reproducibility were assessed for each technique using daily electronic portal
      imaging and were analysed in terms of random and systematic translational and
      rotational displacements of treatment fields with respect to corresponding
      simulation images. In addition, patients completed a short questionnaire aimed at
      determining which technique they preferred. Results showed that random errors for
      the two techniques did not differ significantly. Approximately 80% of random
      translations recorded were less than 3 mm and 80% of random rotations were less
      than 1.5 degrees. Systematic errors showed some improvement with the vac-fix
      system. In the anteroposterior direction, approximately 80% of systematic errors
      were less than 4 mm for both techniques, but in the superoinferior direction the
      80% point was reduced from 5.0 mm for the standard set-up to 2.7 mm for treatment
      in vac-fix. For rotational systematic errors, the corresponding value dropped
      from 1.8 degrees for the standard set-up to 1.1 degrees in vac-fix. Therefore,
      for many patients, additional use of a vac-fix device improved the transfer of
      the planned set-up from simulator to treatment unit. Additionally, answers to the
      questionnaire indicated that patients generally favoured the vac-fix system over
      use of the breast board alone. In conclusion, however, introduction of vac-fix
      immobilization for all patients was not thought justified as the improvements
      demonstrated are not likely to be clinically significant with the present
      treatment technique.

PMID- 11338102
TI  - Influence of radiologists' sex and training on fluoroscopy doses during barium
      enema.
AB  - Variables influencing radiation exposure were studied using analysis of
      covariance in 523 double contrast barium enemas performed by 21 radiology
      residents (12 female, 9 male). Dose-area products (DAPs) (ns), number of
      exposures per patient (p < 0.05) and screening times (p < 0.05) were higher for
      female residents (mean 52.0 Gy cm2, 9.55 exposures and 4.02 min, respectively)
      than for male residents (mean 41.7 Gy cm2, 8.26 exposures and 3.20 min,
      respectively). The number of lectures on radiation protection attended by the
      resident (range 0-20) had no significant effect on these radiation-related
      variables. Other factors explaining these variables were patient age, diagnosis
      and anteroposterior thickness. Radiologists' use of ionizing radiation during
      fluoroscopy may be sex-related. Traditional lecture-based education on radiation
      protection was not effective with this group; thus, improved methods should be
      developed to control doses.

PMID- 11338103
TI  - Calibration frequency of dose--area product meters.
AB  - Calibration of patient dose monitoring devices in diagnostic radiology has become
      increasingly important in the light of new legislation that requires monitoring
      of patient dose against local and national diagnostic reference levels. An
      investigation was conducted into the long-term stability of 41 dose-area product
      (DAP) meters over a period of approximately 5 years, to assess the suitability of
      an annual calibration regimen. For DAP meters fitted to overcouch X-ray tubes,
      77% of calibrations were within 10%, whilst for undercouch tubes only 50% of
      calibrations were within 10%. These findings suggest that annual calibration may
      be too infrequent. Suitable calibration frequencies for different clinical
      workloads are discussed.

PMID- 11338104
TI  - Variation in the probability of cardiac complications with radiation technique in
      early breast cancer.
AB  - Cardiac damage is recognized to be a potentially serious side effect of breast
      cancer radiotherapy, the risk of which may be reduced by the choice of
      appropriate radiotherapy technique. We have previously described variation in
      physical dose to the heart dependent upon radiotherapy technique. In this paper
      we report the calculated improvement in normal tissue complication probability
      (NTCP) (for cardiac damage) achievable by these methods. Cardiac doses were
      calculated from dose-volume histograms (DVHs) using a "Helax" planning system for
      11 patients with left-sided tumours and 5 patients with right-sided tumours. The
      DVH reduction algorithm of Lyman and Wolbarst [1989] was applied to each DVH to
      produce a value for the NTCP. For left-sided tumours, mean NTCP with the standard
      technique was 7.4 +/- 5.6% (range 0.6-17%) and for the optimum technique mean
      NTCP was 0.3 +/- 0.6% (range 0-2%) (p < 0.003 for the difference between the two
      techniques): a predicted reduction in late cardiac complications of 23-fold,
      which is not clearly evident from viewing the DVH raw data.

PMID- 11338105
TI  - Functional imaging as an aid to decision-making in metastatic paraganglioma.
AB  - Malignant paraganglioma is a rare and slow growing tumour of neuroendocrine
      origin. At the time of diagnosis, the tumour is usually widespread, with limited
      therapeutic options. A variety of functional imaging studies are available for
      staging the disease, guiding therapy and monitoring treatment response. These
      include 123I-MIBG or 131I-MIBG, 111In-pentetreotide or 111In-lanreotide
      (somatostatin analogues), and 18F-FDG positron emission tomography. Various
      radionuclides, including 131I and 90Y, can be targeted to the tumour using MIBG
      or pentetreotide. Such targeted radionuclide therapy may provide valuable long
      term palliation in such patients. We present two cases with metastatic
      paragangliomas who had widespread soft tissue and bone metastases. One patient
      was treatment naive and the second had received previous chemotherapy. The
      functional imaging work-up performed and the targeted radionuclide therapies
      considered in these patients are described. Both patients were treated with 131I
      MIBG. Partial tumour response and complete symptomatic and hormonal response was
      achieved in one patient; in the second patient there was no change.

PMID- 11338106
TI  - Haemorrhagic hepatic cyst: a differential diagnosis of cystic tumour.
AB  - A 63-year-old man was found on ultrasound examination to have a hepatic cystic
      mass with a mural nodule, which was mildly enhanced on contrast enhanced CT and
      MRI. At surgery, the cystic fluid was haemorrhagic and histological examination
      of the mural nodule demonstrated an organized haematoma. This case is of interest
      in that an apparent mural nodule was present in a non-neoplastic cyst.
      Haemorrhagic hepatic cyst with an organized haematoma should be included in the
      differential diagnosis of cystic neoplasms.

PMID- 11338107
TI  - Pseudolesion in segment IV of the liver adjacent to the falciform ligament caused
      by drainage of the paraumbilical vein: demonstration by power Doppler ultrasound.
AB  - A case of a pseudolesion in segment IV of the liver, adjacent to the falciform
      ligament, was observed on conventional CT and CT during arterial portography. The
      pseudolesion was caused by drainage of the paraumbilical vein. Power Doppler
      ultrasound was helpful in recognizing this pseudolesion by depicting that the
      paraumbilical vein was connected to vessels in this area. Although the direction
      of flow could not be determined, power Doppler ultrasound is a useful method for
      confirming non-invasively the aetiology of pseudolesions in this area.

PMID- 11338108
TI  - Ischaemic ileal stenosis following blunt abdominal trauma and demonstrated by CT.
AB  - We report a case of blunt abdominal trauma in which delayed ischaemic ileal
      stenosis occurred. A 24-year-old man presented with symptoms and signs of bowel
      obstruction 2 weeks after blunt abdominal trauma. Enhanced CT clearly
      demonstrated a stenotic ileal loop with mural thickening, associated with a
      mesenteric haematoma. This abnormal ileal loop was resected.

PMID- 11338109
TI  - MRI diagnosis of a previously undiagnosed large trabecular ventricular septal
      defect in an adult after multiple catheterizations and angiocardiograms.
AB  - Ventricular septal defect (VSD) is the most frequent congenital heart disease (25
      30%). The diagnosis of VSD is usually made echocardiographically by means of
      colour Doppler ultrasound, and is confirmed by angiocardiography in most cases.
      We describe a case in which an additional large trabecular VSD was demonstrated
      by MRI after previous cardiac catheterizations and angiocardiography in various
      hospitals. MRI allows an exact presentation of the anatomy, including areas that
      are difficult to assess, for instance the apical septum. Determination of cardiac
      output, regurgitation volume and the Qp/Qs quotient in patients with shunt volume
      in heart defects is also possible with one examination.

PMID- 11338110
TI  - The imaging appearances of hydatid disease at some unusual sites.
AB  - On reviewing our cases of hydatid disease seen over a period of 20 years (1978
      1998), we encountered a number of unusual radiological appearances and sites,
      which are demonstrated in this pictorial review. We briefly discuss the pathology
      of hydatid disease and its complications.

PMID- 11338111
TI  - Timer error: the possibility of confusion arising from two different sign
      conventions.

PMID- 11338112
TI  - Comments on the calibration of pre-cut iridium-192 wires for low dose rate
      interstitial brachytherapy using a farmer-type ionization chamber.

PMID- 11338113
TI  - The fog clears.

PMID- 11338114
TI  - Scared of mad cow now?

PMID- 11338115
TI  - Crime and punishment.

PMID- 11338116
TI  - The Mayo Clinic doctor. How to live longer (and love it).

PMID- 11338117
TI  - Holey gene map, Celera!

PMID- 11338118
TI  - Evidence of persisting serum antibodies to Escherichia coli O157
      lipopolysaccharide and Verocytotoxin in members of rural communities in England.
AB  - The techniques of enzyme-linked immunosorbent assay (ELISA) and immunoblotting
      were used to examine a total of 1667 sera, from apparently healthy members of
      rural communities in England, for antibodies to the lipopolysaccharide (LPS) of
      Escherichia coli O157 and Verocytotoxins (VT). Twenty-nine sera from 22
      individuals were shown to have antibodies specific for E. coli O157 LPS. Some of
      these lived on livestock farms and had occupational contact with cattle,
      suggesting that personnel working with farm animals may produce serum antibodies
      to the O157 LPS antigens. Fifteen people had IgG class antibodies to O157 LPS,
      suggesting long-term exposure to E. coli O157 and five people had serum
      antibodies on more than one occasion showing evidence of persistent antibodies to
      O157 LPS. Thirteen sera from 12 of 22 individuals also contained antibodies to
      VT1, VT2 or both toxins. Ten sera contained antibodies to VT1 and VT2, three sera
      contained antibodies to VT2 only.

PMID- 11338119
TI  - Differences of blood pressure estimates between consecutive measurements on one
      occasion: implications for inter-study comparability of epidemiologic studies.
AB  - Currently, substantial variation in epidemiologic studies exists regarding the
      number of blood pressure (BP) readings obtained and the way in which they are
      combined. This might result in systematically different BP estimates. We
      therefore analysed data from 25,891 subjects (10,124 men and 15,767 women) of the
      EPIC-Potsdam Study (European Prospective Investigation into Cancer and Nutrition)
      to estimate the magnitude of differences between consecutive BP readings and
      their combinations. Three measurements with 2 min intervals were performed in the
      sitting position on the right arm with the supported arm elevated at heart level
      by trained interviewers using oscillometric devices. Mean BP declined from first
      to second reading and further to third reading by systolic 5.0/0.9 mmHg in men
      and 4.9/0.8 mmHg in women and by diastolic 1.5/0.3 mmHg in men and 1.9/0.5 mmHg
      in women, as well as pulse pressure (PP) (3.5/0.6 in men, 3.0/0.3 in women) and
      hypertension prevalence (9.1/1.7%-points). The magnitude of BP decline depended
      on BP level, age, body mass index (BMI), and BP medication. Combinations
      including the first reading lead to generally higher estimates than subsequent
      readings or their combination. Published data on mean BP, PP and hypertension
      prevalence depend on the number and subsequent handling of BP readings which
      might introduce bias to the comparison of different studies unless the same
      defined readings were used. The combination of the second and third reading seems
      to be favourable over any single reading or other combinations.

PMID- 11338120
TI  - A cohort study of nutritional factors and endometrial cancer.
AB  - To evaluate the role of nutritional factors in the etiology of endometrial
      cancer, we performed a case-cohort analysis using data from women enrolled in the
      National Breast Screening Study in Canada from 1980 to 1985. For this analysis, a
      subcohort was constructed by selecting a 10% random sample from the 56,837 women
      in the dietary cohort. Cases were the 221 women diagnosed with incident
      adenocarcinoma of the endometrium during follow-up to December 31, 1993 and
      ascertained by record linkage to the Canadian Cancer Database. Information on
      usual diet at enrollment and other epidemiological variables was collected by
      means of self-administered questionnaires. Hazard ratios were obtained from
      proportional hazards regression models, with estimation of robust standard
      errors. We found a strong association of endometrial cancer with body mass index
      > 25 kg/m2 (hazard ratio 2.72, 95% CI: 2.06-3.50). Endometrial cancer risk was
      not associated significantly with intakes of total energy, carbohydrates,
      proteins, total fat and major fatty acids, total dietary fiber and various types
      of fibers, vitamin C, E and A, folic acid, beta-carotene, lutein, or
      cryptoxanthin. Some decrease in risk was noted with relatively high intakes of
      saturated fat, animal fat or lycopene. The associations observed in the study
      were independent of total energy intake and most non-dietary risk factors. The
      study suggests that dietary intakes of energy and most major nutrients are not
      related to the risk of endometrial cancer among Canadian women.

PMID- 11338121
TI  - Salivary testosterone is associated with higher lumbar bone mass in premenopausal
      healthy women with normal levels of serum testosterone.
AB  - The relationships among lumbar and femoral bone mineral density (BMD) and
      different forms of testosterone--total, salivary testosterone and free
      testosterone index (FTI) calculated with the sex hormone binding globulin (SHBG)-
      , body mass index (BMI) and body fat distribution (waist-to-hip ratio and breast
      to-hip ratio) were analysed in a cross-sectional study with 66 Spanish
      premenopausal healthy women aged 42 years and with normal levels of serum
      testosterone. BMD was measured using dual-energy X-ray absorptiometry (Hologic
      QDR 1000), and salivary and blood samples were obtained during early follicular
      phase. In a multiple stepwise regression analysis, lumbar BMD was positively
      predicted by salivary testosterone and negatively by SHBG adjusted by BMI (R2 =
      0.20; p < 0.02). The most femoral BMDs were negatively predicted by SHBG and
      positively by breast-to-hip ratio (R2 = 0.22-0.33, according to the site
      measured), but neck BMD was not predicted by any variable. When FTI was entered
      into the regression model instead of SHBG, it was not an independent predictor of
      BMD. The waist-to-hip ratio was positively correlated with several femoral BMD
      sites, but breast-to-hip ratio was better predictor. After adjusting by SHBG, the
      BMI was only predictor for intertrochanter BMD. All women with elevated salivary
      testosterone (n = 12) had higher lumbar BMD than those with normal value (1.120
      +/- 0.112 vs. 1.026 +/- 0.118; p < 0.01) without differences in other confounding
      variables. As a conclusion, in premenopausal healthy women of the same age with
      normal levels of serum testosterone, low levels of SHBG and high levels of
      salivary testosterone are associated with higher lumbar BMD, whereas low levels
      of SHBG together with higher breast-to-hip ratio are associated with higher
      femoral BMD.

PMID- 11338122
TI  - An outbreak in Italy of botulism associated with a dessert made with mascarpone
      cream cheese.
AB  - In the late 1996, an outbreak of botulism affected eight young people (age of
      patients ranged from 6 to 23 years) in Italy. The onset of the illness was the
      same for all of these patients: gastrointestinal symptoms (nausea and vomiting)
      followed by neurologic symptoms. The most common neurologic symptoms were
      dysphagia, respiratory failure (100%), diplopia (87%), dysarthria, ptosis (75%)
      and mydriasis (50%). All patients required mechanical ventilation. Botulinum
      toxin was detected from two of respectively five sera and six stool samples
      analysed, while spores of Clostridium botulinum type A were recovered from all
      patient' faeces. The epidemiological investigation led to suspect a commercial
      cream cheese ('mascarpone') as a source of botulinum toxin: indeed, it had been
      eaten by all the patients before onset of the symptoms, either alone or as the
      (uncooked) ingredient of a dessert, 'tiramisu'. Botulinum toxin type A was found
      in the 'tiramisu' leftover consumed by two patients and in some mascarpone cheese
      samples collected from the same retail stores where the other patients had
      previously bought their cheeses. A break in the cold-chain at the retail has
      likely caused germination of C. botulinum spores contaminating the products, with
      subsequent production of the toxin. One of the patients died, while the others
      recovered very slowly. Prompt international alerting and recall of the mascarpone
      cheese prevented the spread of the outbreak due to the wide range of
      distribution, demonstrating the importance of a rapid surveillance system. None
      of the people complaining of symptoms after the public alert resulted positive
      for botulinum spores and toxin.

PMID- 11338124
TI  - Hepatitis B and HIV/AIDS in Zagreb: a district level analysis.
AB  - This study examines the presence of hepatitis B as a possible precursor marker
      for HIV/AIDS in 10 districts of Zagreb, Croatia. There were a total of 931 cases
      of hepatitis B in Zagreb in the period 1979-1995, the annual rate ranging from
      3.1 to 15.4 per 10,000. The highest relative risk for hepatitis B for the 1979
      1995 period was in the Pescenica district (Relative risk (RR): 1.4). There were
      108 cases of HIV/AIDS diagnosed in Croatia in the period 1986-1996, with 34% from
      Zagreb. The highest relative risk for HIV/AIDS was within the Pescenica district
      (RR: 2.3). Pescenica had also a significantly higher incidence of hepatitis B
      when compared to other districts (p = 0.005). The cumulative incidence of
      hepatitis B in Zagreb was directly related to levels of neighborhood discomfort
      as determined by an index including unemployment, inflation and housing
      conditions (p = 0.005). This research demonstrates that the poor areas of the
      city with higher incidence of hepatitis B hold the greatest threat for the spread
      of HIV/AIDS.

PMID- 11338123
TI  - Antiretroviral therapy in HIV-infected individuals in clinical practice: are the
      criteria for initiating and choosing the type of drug regimen based only on
      immunologic and virologic values?
AB  - OBJECTIVES: To determine factors associated with beginning antiretroviral therapy
      and with the number of drugs used. METHODS: Longitudinal study of 3169 HIV
      infected individuals naive from antiretroviral drugs at enrollment in 65
      infectious disease clinics in Italy. Initiation of antiretroviral therapy and
      number of drugs used (i.e., < 3 vs. > or = 3 drugs) were the main outcome
      measures. Adjusted odds ratios were calculated by logistic models to establish
      cofactors of these two measures. RESULTS: From January 1997 to December 1998,
      1288 (40.6%) individuals started therapy, 58.0% of whom were given a triple
      combination regimen. This regimen became more frequent over time. By multivariate
      analysis, high levels of HIV-RNA and low CD4 counts were the most important
      independent predictors of starting any type of therapy. A significant association
      was also found with HIV exposure category, reason for being antiretroviral-naive,
      presence/absence of liver disease, presence/absence of a new AIDS-defining
      disease, and clinical centre. High levels of HIV-RNA and low CD4 counts were also
      the most important predictors of starting with > or = 3 drugs, compared to < 3
      drugs, and men had an independent higher probability of starting with > or = 3
      drugs, compared to women. The probability of starting with > or = 3 drugs
      significantly increased with calendar time. CONCLUSIONS: CD4 and HIV-RNA were the
      main cofactors of initiating both any type of therapy and therapy with > or = 3
      drugs. The large variability among clinical centres suggests that clinicians are
      uncertain as to the exact timing of beginning therapy and the specific regimen,
      especially among women.

PMID- 11338125
TI  - Role of hepatitis E and other hepatotropic virus in aetiology of sporadic acute
      viral hepatitis: a hospital based study from urban Delhi.
AB  - Major hepatotropic virus continues to be an important cause of acute viral
      hepatitis (AVH) in developing countries like India. While epidemics of AVH have
      been well studied few serious sporadic cases from developing countries have been
      reviewed. We studied prospectively 75 cases of sporadic AVH who reported to our
      hospital and were evaluated for the presence of various hepatotropic viruses. The
      seroprevalence of IgG anti-HEV antibodies was studied in the general population
      as a control. We found 53.3% (40/75) of sporadic AVH cases were due to hepatitis
      E virus while 11% (8/75) were due to hepatitis B virus. Hepatitis C virus was
      responsible for 8% (6/75) of the sporadic AVH cases and hepatitis A was found in
      5% (4/75) of the cases. No causative agent was found in 23% (17/75) of the
      sporadic AVH cases. The sporadic AVH cases due to HEV were not clinically or
      biochemically not different from AVH due to other viruses. We found a high
      prevalence of IgG anti-HEV in 35.6% (178/500) among the general population of
      urban Delhi. The study suggested that hepatitis E was the most common cause of
      sporadic AVH in urban Delhi. High seroprevalence of IgG anti-HEV antibodies in
      the general population and amongst the sporadic AVH cases suggests that it is
      unlikely to be protective antibody. IgM anti-HEV positive serology is considered
      diagnostic of acute hepatitis E infection in India, where hepatitis E is endemic.

PMID- 11338126
TI  - Evaluation of the SIMI system, an experimental computerised network for the
      surveillance of communicable diseases in Italy.
AB  - In Italy, the current communicable disease notification system is organised as
      follows: in each region, Local Health Units (LHU) fill in and forward case report
      forms (CRF) to the Regional Health Authority, which send aggregated and
      individual notifications to several central-level institutions. In most regions,
      all data are recorded manually on hardcopy. Although most relevant data from CRFs
      are eventually entered into a computerised database at the National Institute of
      Statistics (ISTAT), the national database is only available 3-4 years later and
      no data-quality control is performed at that time. To improve the quality and
      timeliness of notification, in 1994, the Istituto Superiore di Sanita (the
      National Institute of Health) began to develop an experimental computerised
      surveillance network for communicable diseases (referred to as 'SIMI').
      Specifically, a software was created and distributed to the LHUs and the Regional
      Health Authorities; staff training was performed; and feedback and analyses of
      collected data was promoted. SIMI was evaluated in the 13 regions that were
      participating in 1997 (out of a total of 20 regions in Italy), using criteria
      commonly used for surveillance systems (i.e., completeness and coherence of data,
      case definitions, costs, timeliness, and feedback). SIMI was implemented at a
      limited cost and the data collected were observed to have had a high degree of
      completeness and internal consistency. The SIMI system has since been adopted for
      the routine notification of communicable diseases in nearly all regions. Similar
      evaluations will be necessary for assessing the performance of the various
      notification systems used across Europe and to include them in a European
      network.

PMID- 11338127
TI  - Distribution of HCV genotypes among risk groups in Serbia.
AB  - Blood samples from 190 patients that were anti-hepatitis C virus (HCV) positive
      were genotyped and 165 were found to contain HCV-RNA. Genotyping was performed by
      PCR based on type-specific primers (117 isolates) and LiPA test (48 isolates) and
      verifying by sequencing. In Serbia, the most frequent genotype was 1b (49.1%),
      followed by genotype 3 (21.2%) and genotype 1a (8.5%). The frequency of genotypes
      2 and 4 was below 5% and mixed infections were encountered in 9.1% of cases.
      Distribution of genotypes was monitored in different risk groups: intravenous
      drug abusers, patients under blood transfusion, patients with previous history of
      surgery, patients undergoing hemodialysis and those with unknown risk factors.
      Genotype distribution is essentially the same in all the groups, except for the
      patients undergoing hemodialysis and those with previous history of surgery where
      significant difference exists compared with the group with unknown route of
      transmission (p < 0.001 and p < 0.05, respectively). There exists significant age
      dependent genotype 3 distribution in Serbian population (p < 0.01).

PMID- 11338128
TI  - The relationship of different socioeconomic variables and alcohol consumption
      with nighttime fatal traffic crashes in Spain: 1978-1993.
AB  - This paper identifies the variables associated with alcohol-related fatal traffic
      crashes (AFTC) in Spain. In addition, and for the first time in this country,
      these variables are used to describe the trend in AFTC, and to study the
      relationship between AFTC and alcohol consumption over the period 1976-1993. To
      this end, official data were obtained from the Traffic Department (Direccion
      General de Trafico), the National Statistics Institute (Instituto Nacional de
      Estadistica), and from international publications on trends in alcohol
      consumption. Nighttime fatal crashes (NFC) and male-driver single-vehicle
      nighttime fatal crashes (MNFC) were strongly associated with AFTC rates in Spain.
      A further finding was the decrease in NFC and MNFC rates during the period 1978
      1993, though this decrease proved of a lower magnitude than that observed for
      daytime crashes. No relationship was observed between alcohol consumption at the
      population level and NFC or MNFC rates. The fatal crash rate, particularly the
      daytime rate, showed a rise with wealth level, as measured by gross domestic
      product and national private consumption, and an inverse relationship with the
      unemployment rate. The relationship between the fatal crash rate and economic
      variables was due, in most part, to changes in vehicle-km travelled.

PMID- 11338129
TI  - Is there a different dietetic pattern depending on self-knowledge of high blood
      pressure?
AB  - This cross-sectional study describes the dietary pattern seen at recruitment in a
      large Spanish cohort comprising 41,451 people (aged 30-69 years) according to
      high blood-pressure status. We provide information on adjusted mean daily intake
      of foods and nutrients, by means of a dietary history, from those people self
      reported as having high blood pressure as well as from those self-reported as
      normotensive but having, after actual blood-pressure measurement, systolic or
      diastolic blood pressures of > or = 160/95 mmHg. Although with small differences
      in mean intake people who self-reported high blood pressure have a higher
      consumption of potatoes, vegetables, vitamin C and E; furthermore, men reported
      an increased intake of fruit, meat, fish, proteins, dietary fibre, beta-carotene
      and alcohol, and women tended to consume less alcohol, lipids and cholesterol but
      more proteins, carbohydrates and dietary fibre. Almost no differences are found
      in fatty acid intake. This pattern is reversed among those self-reported as
      normotensive but with high blood pressure after actual measurement. We conclude
      that in this large prospective cohort, awareness or not of having high blood
      pressure at recruitment is associated with a differential dietary pattern.

PMID- 11338131
TI  - [Who should do ultrasonography during pregnancy?].

PMID- 11338130
TI  - The effect of physical activity on breast cancer risk: a cohort study of 30,548
      women.
AB  - BACKGROUND: In epidemiological studies abundant physical activity has been
      related to decreased breast cancer risk, though the results have been
      inconsistent. The purpose of this paper was to study the association of physical
      activity at leisure and commuting to work and incidence of breast cancer.
      METHODS: The study cohort consisted of 30,548 female participants of the Finnish
      adult health behaviour survey, based on annual random samples of Finns aged 15
      64, collected in 1978-1993. By the end of 1995, 332 breast cancer cases had been
      diagnosed in the cohort. Relative risks of breast cancer were adjusted for age at
      survey, body mass index (BMI), education, length of follow-up, parity and age at
      first birth using Poisson regression models. RESULTS: Compared to women
      exercising less than once a week, the adjusted relative risk of breast cancer for
      women exercising once a week was 0.80 (95% confidence interval (CI): 0.58-1.10),
      for women exercising 2-3 times per week 0.92 (95% CI: 0.78-1.22) and for women
      exercising daily 1.01 (95% CI: 0.72-1.42). Women who reported commuting, walking
      or bicycling to work 30 min or more daily had slightly lower adjusted risk of
      breast cancer (RR: 0.87, 95% CI: 0.62-1.24) than women working at home, being
      unemployed or driving a car to working place. CONCLUSION: Although a small
      protective effect of regular physical activity for breast cancer incidence was
      found in physical activity when commuting to work, the role of the physical
      activity in breast cancer prevention is still an open question.

PMID- 11338132
TI  - [Management of adnexal tumors: role and risks of laparoscopy].
AB  - The laparoscopic management of adnexal tumeurs remains controversial because of
      the potentials risks of cancer dissemination suggested by many case reports and
      national surveys. From experimental data, the laparoscopic treatment of
      gynecologic cancer has potential advantages and disadvantages. The risk of
      dissemination appears high when a large number of malignant cells are present so
      that adnexal tumors with external vegetations, and bulky lymph nodes may be
      considered as contra-indications to CO2 laparoscopy. Laparoscopic surgery has
      become the gold standard in the treatment of benign adnexal tumeurs, whereas
      laparotomy remains the standard for the treatment of malignant tumors. The
      surgical diagnosis is the key to adequate management of adnexal tumeurs. In our
      experience, after a careful preoperative evaluation, the laparoscopic diagnosis
      of malignancy is reliable. Moreover in national surveys, many malignant tumeurs
      were considered as benign despite suspicious laparoscopic findings. Using strict
      guidelines, laparoscopic diagnosis can be proposed for both non suspicious and
      complex tumeurs, thus avoiding many unnecessary laparotomies for benign tumeurs
      suspicious at ultrasound. The more controversial limits of laparoscopic treatment
      are discussed. If a laparotomy was performed for all tumeurs suspicious at
      surgery, 80% of the cases would be treated by laparoscopy. The role of
      laparoscopy for restaging and second look operations for ovarian cancer requires
      further evaluation.

PMID- 11338133
TI  - [Vaginal hysterectomy:apropos of a series of 1008 interventions].
AB  - STUDY AIM: The aim of this study was to analyse our vaginal hysterectomies
      performed for prolapsed uterus and non prolapsed uterus with benign disease. For
      the latter indication, a comparison was made with abdominal hysterectomy.
      PATIENTS AND METHODS: From february 1986 to december 1998, 1008 vaginal
      hysterectomies were performed in our department: 219 for prolapsed uterus and 789
      for non prolapsed uterus with benign disease. During the same time, 217 abdominal
      hysterectomies were performed for non prolapsed uterus with benign disease.
      RESULTS: Intra-operative and post-operative complications had the same rates in
      the two groups. Owing to the low number of abdominal hysterectomies, we cannot
      draw a valuable conclusion. The study of the literature shows in this field an
      advantage for the vaginal hysterectomy; mean time hospitalization was shorter in
      the vaginal group. CONCLUSION: Advantages of vaginal hysterectomy are multiple:
      aesthetic, shorter hospitalization, quicker recovery. The low rate of vaginal
      hysterectomy on non prolapsed uterus with non malignant disease is linked with
      the lack in training of surgeons for the vaginal approach. In these cases, a rate
      of 70% is a realistic one in a well trained hospital center.

PMID- 11338134
TI  - [External genital excision sequelae at the Yalgado Ouedraogo national central
      hospital: epidemiology and surgical treatment].
AB  - By a prospective study in one year time, the authors noticed that female genital
      mutilation complications were 7.3 per cent of external gynecologic consultations
      and most complications were overdraft between 15 and 24 years old (36 cases out
      of 49). The main consultation motives were dyspareunia and difficult sexual
      relationship. Surgery under local anesthetic was very efficient (more than 90%
      success) and cheaper than surgery under general anesthetic.

PMID- 11338135
TI  - [Predictive value of non-automated spermatic parameters and automated kinetic
      parameters on cleavage rate in fertilization in vitro].
AB  - The aim of this work was to determine retrospectively in 114 couples the
      predictive value of semen analysis for the in vitro fertilization (IVF) outcome
      when sperm evaluation before IVF was assessed by either conventional parameters
      or a Hamilton-Thorne automated motility analyser. A backward logistic regression
      analysis was used to study the relative contribution of each conventional or
      computerized parameter. Computerized sperm values were the worst index for
      predicting oocyte fertilization. However a tight relationship between morphology
      and cleavage ratio was observed. Using ROC analysis, under a 18% threshold,
      cleavage failure was noted in 71% of couples undergoing an IVF program. This
      study indicates that morphology is the best parameter for predicting cleavage
      failure.

PMID- 11338136
TI  - [Incidence, diagnosis and prognosis of ovarian metastasis in breast cancer].
AB  - Ovarian metastasis are frequently encountered during the course of breast cancer,
      concerning one woman in five among those suffering from the disease. These
      secondary ovarian lesions are usually small and bilateral with a non-cystic
      pattern and are more likely to be from primary infiltrating lobular carcinoma of
      the breast. Distinction between ovarian metastasis and primary ovarian cancer may
      sometimes be difficult and require immunohistochemical stains with various
      monoclonal antibodies. Primary ovarian cancer remains preponderant however, even
      in a woman with breast cancer. From a clinical point of view, ovarian metastasis
      are frequently unknown except in case of peritoneal dissemination. Trans-vaginal
      ultrasonography scan is the best examination when clinical signs give cause to
      suspect ovarian tumour. Although, systematic ultrasonography screening, as well
      as blood screening program using CA 125 and CA 15-3, should not be recommended
      because they lack sensibility and are too expensive. The development of ovarian
      metastasis during the course of a breast primary carcinoma is a negative
      prognostic factor with regards to the presence or absence of peritoneal
      dissemination.

PMID- 11338137
TI  - [The new tocolytics].

PMID- 11338138
TI  - [Follicle stimulating hormone and inhibin B in the woman].

PMID- 11338139
TI  - [Reduction of triplet pregnancies: for or against? For].

PMID- 11338140
TI  - [Reduction of triplet pregnancies: for or against? Against].

PMID- 11338141
TI  - New administration, HCFA leadership could mean "kinder and gentler" agency.

PMID- 11338142
TI  - How much do you really know about discharges, transfers?

PMID- 11338143
TI  - Head off regulatory, accreditation, liability woes by following these proven
      documenting strategies.

PMID- 11338144
TI  - Congress, White House repeal OSHA's ergonomics rule.

PMID- 11338146
TI  - Overcoming barriers to breastfeeding: suggested breastfeeding promotion programs
      for communities in eastern Nova Scotia.
AB  - The 1994 rate of initiation of breastfeeding in eastern Nova Scotia was 41%. The
      purpose of this study is to assess both perceived barriers to breastfeeding as
      well as the need for programs to promote breastfeeding in this region. Seventy
      randomly selected subjects (67 F, 3 M) responded to a questionnaire about
      regional breastfeeding practices. Results showed that perceived barriers to
      breastfeeding included lack of knowledge about breastfeeding management (35.8%)
      and lack of support (29.9%). Barriers to exclusive breastfeeding for 6 months
      included going back to work (76.5%) and lack of support (39.2%). To promote
      exclusive breastfeeding for 6 months, participants recommended access to:
      prenatal classes (98.5%), nurse follow-up following hospital discharge (95.3%),
      and availability of lactation consultants (88.3%). When proposed promotion
      programs were implemented, breastfeeding initiation increased to 60.5% and
      duration rates increased to 4 months (90.2%). Regional barriers to breastfeeding
      can be partly alleviated through educational and support programs.

PMID- 11338145
TI  - [Lack of conviction about vaccination in certain Quebec vaccinators].
AB  - A questionnaire was mailed to all vaccinators in Quebec in 1998. The objective of
      this survey was to document vaccinators' attitudes, knowledge, and practices
      related to vaccination. Vaccinators generally believe in the security, efficacy
      and usefulness of vaccines given to young children. However, 41% of nurses do not
      fully agree with these opinions. More than 94% of pediatricians completely
      disagree that "certain practices (homeopathy, good eating habits and a healthy
      lifestyle) can eliminate the need for vaccination", compared with 85% of general
      practitioners and only 60% of nurses. Less than 25% of doctors recall children
      who are late in getting their immunizations; approximately 45% of vaccinators are
      in complete agreement with simultaneous injections of two vaccines; many
      circumstances are incorrectly seen as contra indications for vaccination. Public
      health authorities should target systematic interventions towards vaccinators to
      improve this situation and to increase nurses' conviction regarding the benefits
      of vaccination.

PMID- 11338147
TI  - Bias in maternal reports of smoking during pregnancy associated with fetal
      distress.
AB  - BACKGROUND: Studies examining the adverse effects of smoking during pregnancy
      commonly use maternal reports. We hypothesized that if an adverse event occurred
      during pregnancy, women may underreport smoking. This study looked for bias in
      maternal report of smoking if fetal distress occurs. METHODS: Data were collected
      prospectively from patients attending The MotheRisk Program who smoked during
      pregnancy, and were categorized by delivery outcome, maternal and neonatal
      characteristics, and the raw number of cigarettes smoked per day during pregnancy
      reported at clinic and at follow-up. The difference between these two values was
      compared. RESULTS: 95 women had uneventful deliveries and 25 had fetal distress.
      Women who reported fetal distress decreased their report of smoking after
      delivery compared to their original report during pregnancy, whereas women with
      an uneventful labour did not (p = 0.04). CONCLUSIONS: Our results suggest that if
      an adverse pregnancy outcome occurs, mothers may tend to underreport their
      cigarette consumption.

PMID- 11338148
TI  - Fall-related hospitalizations: what's in season?

PMID- 11338149
TI  - Risk factors for falls and injuries in a long-term care facility in Ontario.
AB  - OBJECTIVE: To identify risk factors for falls and injuries among seniors living
      in a long-term care facility. METHOD: Case-control study of 335 residents living
      at St. Joseph's Villa, Dundas, Ontario. Cases were defined as residents who fell
      between July 1, 1996 and June 30, 1997; controls were those who did not fall. To
      identify risk factors for injury, cases were defined as those with completed
      incident injury forms and controls as those without. RESULTS: The most important
      risk factors for falls included: having fallen in the past three months; residing
      in a secured unit; living in the facility for two or more years; having the
      potential to cause injury to others; and having an illness, disease or behaviour
      that may cause a fall. The most important risk factor for injury among those who
      fell was altered mental state. CONCLUSION: The risk factors identified may be
      helpful to those planning falls prevention initiatives within long-term care
      settings.

PMID- 11338150
TI  - Heart disease risk factor prevalence and profiles in a randomized community
      sample of Canadian women.
AB  - This study examined the prevalence and profiles of behavioural and biomedical
      risk factors of heart disease in a randomized community sample of 843 Canadian
      women. Sociodemographic characteristics were also examined to determine their
      association with women who have multiple primary risk factors versus risk factor
      free women. A greater proportion of high-risk women (n = 81) reported to have
      less education, lower income and employment levels and were more likely to live
      without a partner than women with no primary risk factors (n = 135). These
      findings contribute to the understanding of the growing complexity of addressing
      heart health beyond lifestyle behaviours as articulated by the Victoria (1992),
      Catelonia (1995), Singapore (1998) and Women's International (2000) Declarations
      on Heart Health. Public health planning should continue to address physical
      activity, smoking and dietary behaviours across age groups with a concentrated
      effort to target high-risk, socio-economically disadvantaged women. Risk
      assessment for heart disease must also include sociodemographic characteristics
      for tailoring heart health programs in the community.

PMID- 11338151
TI  - Factors important in promoting cervical cancer screening among Canadian women:
      findings from the 1996-97 National Population Health Survey (NPHS).
AB  - Although routine Pap screening represents an effective tool in the early
      detection of cervical cancer, it remains underused by some Canadian women. This
      study examines selected sociodemographic, health, lifestyle, and system barriers
      to Pap test participation among 33,817 women aged 18+ years in the cross
      sectional 1996-97 National Population Health Survey (NPHS). Among women 18 years
      and over, 87% reported ever having had a Pap test while 72% reported a recent (<
      3 years) test. A report of ever and recent use was most common among women 25-34
      (92% and 86.9%, respectively). Only 0.6% of recently screened women reported
      access problems. Among those without a recent test, most (53%) reported that they
      did not think it was necessary. Pap test use varied little across provinces and
      was less common among older and single women, those with lower education, a
      spoken language other than English, a birth place outside Canada and negative
      health and lifestyle characteristics.

PMID- 11338152
TI  - Survey of infection control procedures at manicure and pedicure establishments in
      North York.
AB  - OBJECTIVE: To describe infection control practices used by technicians doing
      manicures and pedicures in an urban setting in Ontario. METHODS: A random sample
      of 120 establishments was selected from a sampling frame. A survey was designed
      and administered to technicians through face-to-face interviews. RESULTS:
      Technicians in 72 establishments were interviewed, representing a 60% response
      rate. Twenty-nine (40%) of these technicians indicated that they had been
      immunized against hepatitis B. Technicians re-used almost all instruments even if
      this was not the intent of the manufacturer. Isopropyl alcohol was the most
      commonly used disinfectant. Many technicians did not wear gloves while performing
      procedures. Most did not follow universal precautions when asked how they would
      react to incidental cuts on either the client or themselves. CONCLUSION: There is
      a need for the development of infection control protocols for manicure and
      pedicure establishments since the potential for transmission of infectious
      diseases does exist.

PMID- 11338153
TI  - How to find Chinese research participants: use of a phonologically based surname
      search method.
AB  - The frequent use of non-representative, time-consuming and low hit rate sampling
      methods in the study of minority cultures is of concern. Given the increasing
      cultural diversity of the Canadian population and the growing Chinese population,
      a sampling method using phonological rules to distinguish Chinese surnames from
      non-Chinese ones was developed. Chinese surnames, transcribed according to their
      pronunciations, follow specific phonological rules. A flowchart was developed
      using the inclusion and exclusion criteria derived from these rules. Methods to
      validate Chinese surnames (identified from telephone directory) were external
      reference source, expert panel, and telephone interview. A total of 266 possible
      Chinese surnames were selected using the flowchart. External reference source
      validated 153 surnames, expert panel 53, and telephone interview 23. An overall
      hit rate of 86.1% (229/266) was achieved, reflecting the validity of the
      phonological criteria in identifying individuals with a Chinese surname from the
      general population.

PMID- 11338154
TI  - Weight change, nutritional risk and its determinants among cognitively intact and
      demented elderly Canadians.
AB  - Nutritional risk and its predictors were assessed by evaluating longitudinal
      changes in body weight using data collected from elderly community-dwelling and
      institutionalized Canadians who participated in both phases of the Canadian Study
      of Health and Aging, CSHA (n = 10,263). Change in body weight (% initial weight)
      was examined over a 5-year interval in 584 community and 237 institutionalized
      participants, and its predictors tested in multiple and logistic regression
      analyses. Average weight at CSHA-2 was 97% of initial weight at CSHA-1. Values
      were lower in those over 90 years and the demented. Increasing frailty in a 7
      point scale (beta = -1.23, p = 0.04) predicted weight loss in institutional
      participants, as did difficulty in eating unaided (beta = 4.24, p < 0.001) and
      reported loss of interest in life (beta = 2.22, p < 0.001) among community
      subjects. Some 16% in institutions and 9% in the community were at
      moderate/severe nutritional risk, disproportionately represented by the oldest
      subjects and the demented. These analyses support the importance of assessing
      dietary intakes, anthropometrics, well-being and environmental predictors of
      aging in the elderly.

PMID- 11338155
TI  - An introduction to multilevel regression models.
AB  - Data in health research are frequently structured hierarchically. For example,
      data may consist of patients nested within physicians, who in turn may be nested
      in hospitals or geographic regions. Fitting regression models that ignore the
      hierarchical structure of the data can lead to false inferences being drawn from
      the data. Implementing a statistical analysis that takes into account the
      hierarchical structure of the data requires special methodologies. In this paper,
      we introduce the concept of hierarchically structured data, and present an
      introduction to hierarchical regression models. We then compare the performance
      of a traditional regression model with that of a hierarchical regression model on
      a dataset relating test utilization at the annual health exam with patient and
      physician characteristics. In comparing the resultant models, we see that false
      inferences can be drawn by ignoring the structure of the data.

PMID- 11338156
TI  - Hospitalization for ambulatory care-sensitive conditions: a method for
      comparative access and quality studies using routinely collected statistics.
AB  - BACKGROUND: Appropriate and timely provision of ambulatory care is an important
      factor in maintaining population health and in avoiding unneccessary hospital
      use. This article describes conditions for which hospitalization rates have a
      strong and inverse relationship to access to high-quality ambulatory care.
      METHODS: Three panels of Canadian physicians following different consensus
      techniques selected conditions for which the relative risk of hospitalization is
      inversely related to ambulatory care access. PRINCIPAL FINDINGS: All panels
      identified asthma, angina pectoris, congestive heart failure, otitis media,
      gastric ulcer, pelvic inflammatory disease, malignant hypertension, and
      immunization-preventable infections as ambulatory care-sensitive admissions.
      These conditions strongly overlap with lists developed for similar purposes in
      the U.S. and England. INTERPRETATION: Ambulatory care-sensitive conditions
      represent an intermediate health outcome. They are distinct from inappropriate
      hospitalizations. They may be useful for measuring the impact of health care
      policy, and for performance measurement or audit.

PMID- 11338157
TI  - Putting the public back into public health: one city's experience.

PMID- 11338158
TI  - "Playing on shifting sand": reflections on the impact of political shifts on
      community action and public health.

PMID- 11338159
TI  - Tobacco industry litigation and the role of government: a public health
      perspective.

PMID- 11338160
TI  - Community action success in public health: are we using a ruler to measure a
      sphere?
AB  - The Community Action and Public Health study explored how Ontario public health
      practitioners interpret and implement guidance in community action. In-depth
      interviews were conducted with 107 public health professionals and community
      members in 6 Ontario health units. This report briefly describes the study
      methods and presents results pertaining to the measurement of success based on
      interviews with 67 public health professionals. Data substantiate the view that
      evaluation methodologies employing quantitative measures of epidemiological
      outcomes inadequately capture "success" in community action, possibly
      attributable to an unproductive dichotomization of "process" and "outcome".
      Results suggest two kinds of "success": a) changes related to stated goals and
      targets; and b) more iterative and process-oriented changes, including necessary
      but often undocumented shifts in relationships, structures, social conditions and
      processes. In order to legitimize and validate results that might otherwise pass
      unrecognized, we suggest a methodology that records project "milestones" as
      successes in their own right.

PMID- 11338161
TI  - The north-south gradient in health: analytic applications for public health.
AB  - Health in the northern territories does not reach that of national standards.
      Investigations in these areas are hampered by small population size, which limits
      both the identification of local health problems as well as the planning and
      prioritizing of prevention and interventions. We report on health deficiencies of
      the northern territories and illustrate how our analytic applications supplement
      traditional approaches to benefit public health objectives. We reveal that life
      expectancy in Northern Canada has increased such that health deficiencies between
      the North and South have decreased substantially, although they still persist at
      a high level. The current health status of Northwest Territories residents
      approximates that of Canadians 15 to 25 years ago. In addition, while chronic
      diseases were previously less of a concern for Northwest Territories residents,
      they show increasing trends in importance. This is of particular significance in
      light of an aging population in the northern territories.

PMID- 11338162
TI  - How many surgeons does a province need, and how do we determine appropriate
      numbers?
AB  - The study compared each province's supply of surgeons in three specialities
      (ophthalmologists--orthopedic--surgeons, and cardiac and thoracic surgeons) with
      the rates of key procedures (cataract removal, hip and knee replacement, and
      coronary artery bypass) that residents received. We found little or no
      relationship between the supply of surgeons and a population's surgery rate. We
      conclude that the supply of surgical specialists is the wrong focus for health
      care resource planning.

PMID- 11338163
TI  - Preventing and resolving ethical conflicts: more help for policy makers.
AB  - Institutional policy makers have a useful resource in the "Joint Statement on
      Preventing and Resolving Ethical Conflicts Involving Healthcare Providers and
      Persons Receiving Care". Yet, some aspects of the joint statement pose challenges
      for institutional policy development and merit further reflection. With the aim
      of clarifying and augmenting the recommendations in the joint statement, this
      paper gives additional guidance on the issues of benefit, power imbalance, and
      legitimate decisional authority.

PMID- 11338164
TI  - A pilot study on home visiting in Aspen Community Care Services.
AB  - The aim of this study was to test a questionnaire for more detailed management
      information of a community care program in rural Alberta. A total of 24 community
      care clients and 486 home visits to these clients were assessed. The Client
      Homebound Score (CHS) and the Case Management Intensity Score (CMIS) were
      positively associated with time spent on home visits. These scores would be
      useful indicators for improved resource-based planning of home visiting.

PMID- 11338165
TI  - Thriving in a changing environment.
AB  - Undeniably, working in an environment that challenges the status quo is not
      without its problems. Members of the service redesign teams who participated in
      the West Ottawa Valley Network experience confess that many times during the
      process they felt a threat to their own job security along with uncertainty about
      their future roles and responsibilities. June Merkley points out that "working
      outside one's "normal comfort level" in a non-traditional leadership role has
      it's own set of difficulties, and dealing with multiple network members adds a
      dimension of complexity not encountered at the single site level." But she
      believes that "the challenges encountered within the network are helping to
      broaden the scope of job knowledge and communication skills. This can only have a
      direct and positive impact on the day-to-day tasks, while providing value to both
      the employee and employer". As a career management strategy, healthcare managers
      should seek out opportunities beyond their normal range of accountability,
      participate in activities that encourage the growth of new skills or hone skills
      that are a bit rusty. Often these projects will cause some anxiety or discomfort
      but the rewards, both short and long term, far outweigh the short-term pain.

PMID- 11338166
TI  - Where is the new $500 million going to go?

PMID- 11338167
TI  - The 360 degrees feedback process: a tool for continuous board improvement.
AB  - To remain accountable to stakeholders, healthcare governing boards need
      meaningful and actionable feedback on their performance.  In 1998, the Board of
      Governors of West Park Hospital (now West Park Healthcare Centre) used the 360
      degree feedback technique for the first time to gather feedback from a range of
      stakeholders. Boards members found the technology accessible and the process
      valuable.  They are using the individual results to improve individual
      performance, and have developed work plans to address areas for continued board
      development.

PMID- 11338168
TI  - From database to deal making: using member information to enhance careers.
      Interview by Matthew D. Pavelich.

PMID- 11338169
TI  - Wanted: hot industry seeks supergeeks.

PMID- 11338170
TI  - More abortions, fewer crimes?

PMID- 11338171
TI  - Celiac vagotomy reduces suppression of feeding by jejunal fatty acid infusions.
AB  - We investigated the role of the celiac branch of the vagus nerve in suppression
      of food intake produced by jejunal fatty acids infusions. Following selective
      celiac vagotomy or sham surgery, adult, male Sprague-Dawley rats received 7 h
      infusions of linoleic acid or saline through indwelling jejunal catheters on four
      consecutive days. Although linoleic acid still produced significant suppression
      of intake in rats with celiac vagotomy, it was less effective in these animals
      than in controls. The temporal pattern of results suggested that celiac afferent
      fibers are involved in mediating both pre- and postabsorptive effects of infused
      fatty acids.

PMID- 11338172
TI  - Hearing the sound of silence: a magnetoencephalographic study.
AB  - We visualized the brain activity for retrieval imagery of a sound using dual 37
      channel magnetometers in seven right-handed healthy subjects. A soundless video
      image of a hammer striking an anvil was presented on a screen. Significantly
      larger evoked magnetic fields were recorded, dominantly in the right hemisphere,
      in six subjects when they imagined the sound than when they did not. The initial
      peak of the response was 151.0 +/- 26.5 ms (mean +/- s.d.) after the blow.
      Equivalent current dipoles (ECDs) for the responses recorded from the right
      hemisphere were located around the inferior frontal sulcus in three subjects and
      in the insular region in three subjects, but reliable ECDs were not estimated
      from the left hemisphere. The results suggested that the initial activity for
      sound retrieval imagery appeared around the inferior frontal and insular areas,
      dominantly in the right hemisphere.

PMID- 11338173
TI  - Association between mu opioid receptor gene polymorphisms and Chinese heroin
      addicts.
AB  - Mu opioid receptor (MOR) has been shown to be associated with alcoholism and
      opioid dependence. The present study examined the involvement of a polymorphism
      in A118G in exon 1 and C1031G in intron 2 of the MOR gene in 200 Chinese heroin
      dependent and 97 control subjects. Results showed a significant association for
      both A118G and C1031G polymorphisms and opioid dependence. The G allele is more
      common in the heroin-dependent group (39.5% and 30.8% for A118G and C1031G
      polymorphisms, respectively) when compared to the controls (29.4% and 21.1% for
      A118G and C1031G polymorphisms, respectively). This study suggests that the
      variant G allele of both A118G and C1031G polymorphisms may contribute to the
      vulnerability to heroin dependence.

PMID- 11338174
TI  - Phenytoin inhibits isolation-induced aggression specifically in rats with low
      serotonin.
AB  - Phenytoin is a widely used anticonvulsant drug that also reduces aggressive
      behavior. Aggression in humans and animals is often associated with low serotonin
      levels. This study examined the anti-aggressive properties of phenytoin in rodent
      isolation-induced aggression using a resident-intruder test to quantify
      aggression. Chronic treatment with p-chlorophenyl-alanine (PCPA), a competitive
      inhibitor of serotonin synthesis, significantly enhanced resident attack behavior
      compared to saline-treated control rats. Phenytoin dose-dependently reduced
      aggressive behavior specifically in PCPA-treated rats, but had no anti-aggressive
      properties in saline-treated rats. These data suggest that aggressive behavior in
      this model may be related to neuronal hyperexcitability that is sensitive to the
      anticonvulsant effects of phenytoin. Further, these data suggest isolation
      induced aggression in PCPA-treated rats may be a useful model to investigate
      aggression associated with low serotonin in the brain.

PMID- 11338175
TI  - Intermuscular coherence in Parkinson's disease: effects of subthalamic nucleus
      stimulation.
AB  - It remains unclear how high frequency stimulation of the subthalamic nucleus
      (STN) improves parkinsonism. We hypothesized that stimulation may affect the
      organization of the cortical drive to voluntarily activated muscle. Normally this
      is characterized by oscillations at 15-30 Hz, manifest in coherence between
      muscles in the same frequency band. We therefore investigated the effects of STN
      stimulation on electromyographic (EMG) activity in co-contracting distal arm
      muscles in nine subjects with Parkinson's disease off drugs. Without stimulation,
      coherence between EMG signals was diminished at 15-30 Hz compared with nine
      controls. STN stimulation increased coherence in the 15-30 Hz band, so that it
      approached that in healthy subjects. The results suggest that STN stimulation
      facilitates the normal cortical drive to muscles.

PMID- 11338176
TI  - Beware and be aware: capture of spatial attention by fear-related stimuli in
      neglect.
AB  - Stimuli with threat significance may be privileged in summoning attention,
      allowing fast detection even outside the field of attention. We studied patients
      with unilateral neglect and visual extinction, who usually remain unaware of
      contralesional stimuli presented together with concurrent ipsilesional stimuli,
      to learn whether emotional stimuli might differentially be affected by
      contralesional extinction. Pictures of spiders or flowers with similar features
      were presented in right, left, or both fields. On bilateral trials, the patients
      detected emotional stimuli (spiders) on the left side much more often than
      neutral pictures (flowers). While mechanisms of spatial attention are impaired
      after parietal damage in neglect patients, intact visual pathways to the ventral
      temporal lobe and amygdala might still mediate distinct mechanisms of emotional
      attention.

PMID- 11338177
TI  - Fluoxetine reduces L-DOPA-derived extracellular DA in the 6-OHDA-lesioned rat
      striatum.
AB  - We investigated the effect of fluoxetine, a selective serotonin reuptake
      inhibitor (SSRI), on L-DOPA-derived extracellular dopamine (DA) levels in the
      striatum of rats with nigrostriatal dopaminergic denervation using in vivo
      microdialysis. Treatment with fluoxetine (10 mg/kg, i.p.) induced a 41% reduction
      in the cumulative amount of extracellular DA during 300 min following L-DOPA
      administration (50 mg/kg, i.p.; p < 0.01). This effect was antagonized by
      pretreatment with WAY-100635, a potent 5-HT1A antagonist, indicating that this
      effect of fluoxetine is due to its indirect 5-HT1A agonistic property. These
      results suggest that SSRIs may impair motor functions in patients with
      Parkinson's disease by reducing efflux of exogenous L-DOPA-derived DA.

PMID- 11338178
TI  - Human neural stem cells improve cognitive function of aged brain.
AB  - The capability for in vitro expansion of human neural stem cells (HNSCs) provides
      a well characterized and unlimited source alternative to using primary fetal
      tissue for neuronal replacement therapies. The HNSCs, injected into the lateral
      ventricle of 24-month-old rats after in vitro expansion, displayed extensive and
      positional incorporation into the aged host brain with improvement of cognitive
      score assessed by the Morris water maze after 4 weeks of the transplantation. Our
      results demonstrate that the aged brain is capable of providing the necessary
      environment for HNSCs to retain their pluripotent status and suggest the
      potential for neuroreplacement therapies in age-associated neurodegenerative
      disease.

PMID- 11338179
TI  - The mineralocorticoid receptor expression in the mouse CNS is conserved during
      development.
AB  - Using a specific polyclonal antiserum raised in rabbit against amino acids 1-23
      of the mouse mineralocorticoid receptor (MR) we investigated the developmental
      profile of MR expression in the murine CNS by immunocytochemistry. MR protein
      appeared first at embryonic day E16.5 in the limbic system, i.e. in the
      hippocampus and induseum griseum. During development and in adulthood, high
      levels of MR expression were observed in the limbic system, whereas expression
      levels detectable in layers II, III, V of the neocortex and in motoneurons of
      cranial nerves and spinal cord were lower. No MR staining was found in the
      hypothalamus. Developmental MR expression was restricted to neuronal populations
      that also express MR protein in the adult CNS, indicating that the MR may fulfill
      the same functions in neurons during development and in adulthood.

PMID- 11338180
TI  - Annexin VII: an astroglial protein exhibiting a Ca2+-dependent subcellular
      distribution.
AB  - A fundamental issue in neuronal and glial cells is how intracellular rises in
      Ca2+ are coupled to signaling cascades and changes in subcellular morphology. We
      studied the expression and localization of annexin VII (synexin), a Ca(2+)-/GTP
      dependent membrane fusion protein, in the human CNS. Here, we demonstrate the
      presence of two annexin VII isoforms (47 and 51 kDa) in human brain tissue as
      well as its exclusive expression in astroglial cells. An in vitro study of
      astrocyte-derived C6 rat glioblastoma cells expressing a GFP tagged annexin VII
      fusion protein demonstrates a sequential redistribution of the fusion protein in
      response to rising intracellular Ca2+ concentrations. Our findings indicate a
      role of annexin VII in the regulation of intracellular Ca(2+)-dependent processes
      in astroglial cells.

PMID- 11338181
TI  - Nociceptin/orphanin FQ inhibits stress- and CRF-induced anorexia in rats.
AB  - The purpose of this study was to examine whether nociceptin/orphanin FQ (NC), the
      endogenous ligand of the opioid receptor-like 1 (ORL1) receptor, is able to block
      hypophagia induced by either stress or central administration of corticotropin
      releasing factor (CRF) in rats. A marked reduction in food consumption was
      observed following exposure to 15 min intermittent electric footshock, 60 min
      physical immobilization or after intracerebroventricular (i.c.v.) injection of
      CRF (0.1-1.0 microgram/rat). i.c.v. pretreatment with NC (0.1-2.0 micrograms/rat)
      completely abolished the hypophagic effect induced by stress or by i.c.v. CRF
      injection. The same i.c.v. doses of NC did not modify food consumption in food
      deprived rats and did not modify the anorexic effect induced by
      lipopolysaccharide, suggesting that the effect of NC is selective for anorexia
      induced by stress or CRF. These findings provide original evidence that NC
      attenuates stress-induced anorexia, presumably by acting as a functional CRF
      antagonist.

PMID- 11338182
TI  - Uptake of fibrillar beta-amyloid by microglia isolated from MSR-A (type I and
      type II) knockout mice.
AB  - To characterize the receptors involved in binding fibrillar amyloid A-beta (fA
      beta), we compared the uptake of fA beta in microglia from wildtype (MSR-A+/+)
      and MSR-A knockout (MSR-A-/-) mice. On average, there was a 60% reduction in the
      uptake of Cy3-fA beta in microglia from the MSR-A-/- mice. Cy3-fA beta uptake in
      the MSR-A-/- mice was still competable by scavenger receptor ligands, including
      acetylated low-density lipoprotein (Ac-LDL) and fucoidan. This indicates that
      uptake by MSR-B and/or other MSRs is also involved in the uptake of fA beta by
      microglia. However, the significant reduction in the uptake of fA beta in the MSR
      A-/- microglia suggests that fA beta gets internalized mostly by MSR-As in
      microglia. Uptake of modified fA beta (ClqA beta) was similar in the MSR-A-/-
      microglia as in the wildtype indicating that the uptake of the opsonized fA beta
      is independent of MSR-A.

PMID- 11338183
TI  - 6-hydroxydopamine increases hydroxyl free radical production and DNA damage in
      rat striatum.
AB  - Oxidative damage is considered to be an important factor of 6-hydroxydopamine (6
      OHDA) toxicity. To address this issue, microdialysis probes were implanted into
      the striatum of Wistar rats and perfused with 6-OHDA. Salicylate was included in
      the perfusion fluid to measure 2,3-dihydroxybenzoic acid (2,3-DHBA) as a marker
      of hydroxyl radical formation using HPLC with electrochemical detection.
      Additionally, striatal tissue was analysed for DNA base alterations using gas
      chromatography-mass spectrometry. 6-OHDA administration resulted in a rapid and
      substantial 6.6-fold increase in 2,3-DHBA formation and also increased levels of
      the modified DNA bases 5-hydroxycytosine, hypoxanthine and 2,6-diamino-4-hydroxy
      5-formamidopyrimidine. Hydroxyl radical formation and DNA base alterations are
      early phenomena of 6-OHDA toxicity and provide clues to the processes that may be
      involved in the initiation of cell death in Parkinson's disease.

PMID- 11338184
TI  - Inflammatory stimuli increase prostaglandin D synthase levels in cerebrospinal
      fluid of rats.
AB  - To examine the possibility that prostaglandin D synthase in CSF is involved in
      the brain responses to inflammation, we monitored the enzyme levels before and
      after administration of a bacterial endotoxin lipopolysaccharide (LPS) or
      proinflammatory cytokines. After an i.p. injection of LPS, the synthase levels
      began to rise within 1 day, peaked at 2 days and returned to the basal by 5 days
      after injection. The enzyme levels increased in a similar manner in response to
      tumor necrosis factor-alpha or interleukin (IL)-1 beta injected i.v. Centrally
      administered IL-1 beta had a similar effect. These findings support the
      hypothesis that PGD synthase in CSF participates in the brain responses to
      inflammation.

PMID- 11338185
TI  - Initial demonstration of rhythmic Per gene expression in the hypothalamus of a
      non-mammalian vertebrate, the house sparrow.
AB  - In mammals, the major pacemaker controlling circadian rhythmicity is located in
      the hypothalamic suprachiasmatic nuclei which are characterized by specific
      molecular features including the expression of three homologues of the Drosophila
      clock gene period (per). Until now, no comparable structure has been
      unambiguously described in the brain of any non-mammalian vertebrate. We cloned
      the PAS-domain of the Per2 gene in the house sparrow (Passer domesticus), a model
      organism in circadian research. Hypothalamic expression of passerPer2 (pPer2)
      showed a marked diurnal rhythm in the suprachiasmatic nucleus, a cell group
      located in the anterior hypothalamus directly above the optic chiasm and adjacent
      to the third ventricle. Additionally, pPer2 was diurnally expressed in the
      lateral hypothalamus. This first demonstration of rhythmic clock gene expression
      in the hypothalamus of a non-mammalian vertebrate provides basic information for
      future research on the evolution of circadian pacemaking systems.

PMID- 11338186
TI  - Neural substrates involved in imitating finger configurations: an fMRI study.
AB  - Imitation plays a very important role in human cognition. Because previous
      neuroimaging studies on human imitation used rather simple actions as target
      stimuli, some aspects of imitation such as perceiving target actions or
      manipulating one's own mental image could not be studied. We used complicated non
      symbolic (S-) and symbolic (S+) finger configurations as target stimuli in order
      to study the neural substrates involved in the perception of target actions and
      mental image manipulation during imitation. Bilateral supramarginal gyrus
      activation was detected when the S- condition was compared with the S+ condition.
      Our result suggests the involvement of the supramarginal gyrus especially for the
      imitation of novel actions.

PMID- 11338187
TI  - Dopamine regulates brain-derived neurotrophic factor (BDNF) expression in
      cultured embryonic mouse striatal cells.
AB  - The differentiation of striatal GABAergic neurons coincides with the perinatal
      establishment of nigrostriatal dopaminergic synaptic connections. We have shown
      previously that dopamine stimulates the maturation of striatal GABAergic neurons.
      Since BDNF also regulates the development of GABAergic cells, we hypothesized
      that dopamine might affect striatal BDNF expression. The influence of dopamine on
      BDNF protein/mRNA and trkB mRNA levels was studied in neuronal and astroglia
      cultures of the mouse striatum. Stimulation with dopamine and a dopamine D1
      receptor agonist increased BDNF mRNA and protein but not trkB mRNA in neuronal
      cultures. Our data indicate a potential role for dopamine in the developmental
      regulation of striatal BDNF expression and suggest that dopamine effects on
      GABAergic cells may be intertwined with BDNF action.

PMID- 11338188
TI  - Novel splice variants of PACAP gene in mouse cerebellar granule cells.
AB  - The mouse pituitary adenylate cyclase activating polypeptide (PACAP) gene
      consists of two alternative exons (1A and 1B) and four exons including the coding
      region. By the usage of alternative exons, three transcripts can be produced. In
      this report, however, we found that at least five preproPACAP transcripts,
      including two novel types, were produced in mouse cerebellar granule cells (CGCs)
      and their expression was induced by the Ca2+ influx through L-type voltage
      dependent Ca2+ channels. The splicing occurred between the 3'-donor site of exon
      1A and the two novel internal 5'-acceptor sites of exon 1B. These findings
      suggest that preproPACAP transcripts are produced by the complicated usage of the
      5'-untranslated region in an activity-dependent manner.

PMID- 11338189
TI  - Evidence for the involvement of the ventro-medial prefrontal cortex in a short
      term storage of visual images.
AB  - The purpose of this study was to clarify the role of the ventro-medial prefrontal
      cortex in short-term visual memory. Patients with focal lesions to the right
      gyrus rectus were impaired on a size judgement task, which required short-term
      retention of laterally presented visual patterns. The impairment was most evident
      when the stimuli were addressed to the damaged hemisphere (left visual field
      presentations) and when separated by very short (50-500 ms) intervals. The
      findings suggest that the ventro-medial part of the orbitofrontal cortex, like
      the ventro-lateral part, is involved in short-term storage of icon-like
      representations of visual objects, and also that there exists a right-hemispheric
      specialization for that function. Our study presents the first direct evidence of
      such specific memory effects in humans using a lesion method and points to the
      importance of the right gyrus rectus area in maintaining the representation of
      stimuli after they are removed from view.

PMID- 11338190
TI  - Mouse hippocampo-prefrontal paired-pulse facilitation and long-term potentiation
      in vivo.
AB  - To confirm neural plasticity of the mouse hippocampo-prefrontal cortex (PFC)
      pathway, paired-pulse facilitation (PPF) and long-term potentiation (LTP)
      induction were determined in the pathway. In addition, we tested whether the
      plasticity differs in projections of the pathway from the dorsal (upper) and
      ventral (lower) parts of the temporal hippocampus. The results showed PPF and LTP
      of this pathway, and these differed between the projections. The projection from
      the upper part showed stronger PPF and weaker LTP compared with that from the
      lower part. These results suggest that the mouse hippocampo-PFC pathway is
      involved in learning and memory, and contains projections related to different
      functions.

PMID- 11338191
TI  - fMRI auditory language differences between dyslexic and able reading children.
AB  - During fMRI, dyslexic and control boys completed auditory language tasks (judging
      whether pairs of real and/or pseudo words rhymed or were real words) in 30 s 'on'
      conditions alternating with a 30 s 'off' condition (judging whether tone pairs
      were same). During phonological judgment, dyslexics had more activity than
      controls in right than left inferior temporal gyrus and in left precentral gyrus.
      During lexical judgment, dyslexics were less active than controls in bilateral
      middle frontal gyrus and more active than controls in left orbital frontal
      cortex. Individual dyslexics were reliably less active than controls in left
      insula and left inferior temporal gyrus. Dyslexic and control children differ in
      brain activation during auditory language processing skills that do not require
      reading.

PMID- 11338192
TI  - Self-monitoring in schizophrenia revisited.
AB  - According to a widespread theory, the first-rank symptoms such as delusions of
      control or thought insertion met in schizophrenia result from a failure in
      predicting the consequences of an action on the basis of a forward model based of
      the intended motor commands (efference copy). This assumption of an impairment in
      the central monitoring of their own actions is inferred from experiments showing
      that it is more difficult for schizophrenic patients than for controls to correct
      erroneous movements in the absence of visual feedback. In our study, 19
      schizophrenic patients (10 with Schneiderian symptoms and nine without) and 19
      paired control subjects were subjected to a sensorimotor adjustment task to
      reassess this hypothesis. We show that the patients who succeeded the task not
      differently from the control subjects were those who were aware of the manual
      correction (n = 9). Surprisingly, most of them presented Schneiderian symptoms.
      This suggests that the experience of alien control observed in certain
      schizophrenic patients cannot be directly related to an underlying cognitive
      deficit in the conscious monitoring of their own actions.

PMID- 11338193
TI  - An event-related potential study of contextual modifications in a face
      recognition task.
AB  - Event-related potentials (ERP) were recorded during a task involving the short
      term recognition of unfamiliar faces. The purpose was to study the effects of
      changing the intrinsic context (facial expression) and/or the extrinsic context
      (background) between the encoding and recognition of a face. The new face caused
      an increase in the parietal N170 amplitude, but this component was not affected
      by contextual modifications. In contrast, the frontal N200 was very sensitive to
      context changes. There was also a well-defined, late parietal component modulated
      by the processing of information relevant to the face recognition decision. This
      late positive component reached its amplitude peak when the decision criterion
      was the strictest. The results obtain showed that ERP can be modulated by these
      context variations even though they are irrelevant to the task at hand.

PMID- 11338194
TI  - An investigation of sensory deficits underlying the aphasia-like behavior of
      macaques with auditory cortex lesions.
AB  - Bilateral auditory cortex lesions in Japanese macaques result in an aphasia-like
      deficit in which the animals are unable to discriminate two forms of their coo
      vocalizations. To determine whether this deficit is sensory in nature, two
      monkeys with bilateral lesions were tested for their ability to discriminate
      frequency and frequency change. The results indicated that although the animals
      were able to discriminate between sounds of different frequencies, they were
      unable to determine whether a sound was changing in frequency. Because the
      animals' coo vocalizations differ primarily in the predominant direction of their
      frequency change and not in their absolute frequency content, the aphasia-like
      deficit of animals with bilateral auditory cortex lesions appears to be a sensory
      disorder.

PMID- 11338195
TI  - Smoking and balance: correlation of nicotine-induced nystagmus and postural body
      sway.
AB  - Unaccustomed smoking may elicit transient nystagmus, dizziness, unsteadiness, and
      nausea. Infrared videonystagmography and posturography were performed
      simultaneously to study the differential effects of nicotine on the association
      of ocular motor and postural disturbances in 25 non- or occasional smokers.
      Sixteen showed nicotine-induced nystagmus (NIN) of various directions (mainly
      horizontal or upbeat) which was associated with a significant increase in
      postural sway after smoking a cigarette (total sway path (SP) before smoking 2.22
      +/- 0.82 m/min (mean +/- s.d.), 1 min after smoking 3.83 +/- 1.41 m/min; p <
      0.0004, ANOVA); nine showed neither effect. There was a high correlation between
      the intensity of the nystagmus (measured as peak slow phase velocity) and the
      increase in total SP (correlation coefficient 0.78) as well as the time courses
      of both. Visual fixation of an LED integrated in the mask not only caused a
      suppression of NIN but also a decrease in body sway. Transient ocular motor and
      postural effects are compatible with simultaneous nicotine-induced effects on the
      vestibulo-ocular and vestibulo-spinal functions.

PMID- 11338196
TI  - Upper/lower visual field asymmetry on a spatial relocation memory task.
AB  - The purpose of this study was to investigate whether the lower visual field
      advantage reported on a number of visual tasks depends on the activity of neural
      systems which process information from different spaces. To this end, a double
      dissociation logic was followed by observing the effects of visual and spatial
      interference on a relocation memory task performed by 80 volunteers. Results
      showed that participants were better at relocating stimuli presented in the lower
      than in the upper visual field. Moreover, a concurrent spatial task, but not a
      concurrent visual task, disrupted the visual field vertical asymmetry. Those
      findings confirm that the vertical asymmetry of visual field depends on the
      spatial processing of incoming stimuli.

PMID- 11338197
TI  - Performance-enhancing effects of CRF-BP ligand inhibitors.
AB  - Intracerebroventricular (i.c.v.) administration of corticotropin-releasing factor
      (CRF) peptide fragments with low affinity for CRF receptors reportedly improves
      cognitive performance without producing anxiety. These compounds are hypothesized
      to act by displacing endogenous peptide from the CRF-binding protein (CRF-BP). To
      test this hypothesis, the present study determined whether the performance
      enhancing potency of CRF fragments was related to their affinity for the CRF-BP.
      Rank ordering of the optimal doses of these compounds for facilitating spatial
      navigation corresponded to their affinity for the CRF-BP. i.c.v. pretreatment
      with performance-enhancing doses of r/h CRF(1-41)-OH (5 micrograms) or r/h CRF(6
      33) (25 micrograms) did not increase emotionality. These findings replicate the
      dissociability of the cognition- and anxiety-related effects of CRF-related
      compounds and suggest that CRF fragments facilitate performance via the CRF-BP.

PMID- 11338198
TI  - Risk assessment of alcohol withdrawal seizures with a Kohonen feature map.
AB  - Recently, it has been suggested that alcohol-induced hyperhomocysteinaemia in
      patients suffering from chronic alcoholism might be a risk factor for alcohol
      withdrawal seizures. In the present follow-up study 12 patients with chronic
      alcoholism who suffered from withdrawal seizures had significantly higher levels
      of homocysteine (Hcy) on admission (71.43 +/- 25.84 mol/l) than patients (n = 37)
      who did not develop seizures (32.60 +/- 24.87 mol/l; U = 37.50, p = 0.0003).
      Using a logistic regression analysis, withdrawal seizures were best predicted by
      a high Hcy level on admission (p < 0.01; odds ratio 2.07). Based on these
      findings we developed an artificial neural network system (Kohonen feature map,
      KFM) for an improved prediction of the risk of alcohol withdrawal seizures. Forty
      nine patients with chronic alcoholism (12 with alcohol withdrawal seizures and 37
      without seizures) were randomized into a training set and a test set. Best
      results for sensitivity of the KFM was 83.3% (five of six seizure patients were
      predicted correctly) with a specificity of 94.4% (one false positive prediction
      of 19 patients). We conclude that in patients with alcohol-induced
      hyperhomocysteinaemia the KFM is a useful tool to predict alcohol withdrawal
      seizures.

PMID- 11338199
TI  - Nitrotyrosination contributes minimally to toxicity of mutant SOD1 associated
      with ALS.
AB  - Enhanced production of nitrotyrosine and subsequent protein nitration has been
      proposed as the mechanism by which mutant SOD1 causes death of motor neurons in a
      familial form of amyotrophic lateral sclerosis (FALS-1). We have tested this
      hypothesis in a primary culture model in which mutant human SOD1 was expressed in
      motor neurons of dissociated spinal cord cultures. Preventing formation of
      nitrotyrosine by inhibiting nitric oxide synthase rescued cultured motor neurons
      from excitotoxic death induced by adding glutamate to the culture medium, but
      failed to significantly delay death of motor neurons expressing the G93A mutant
      SOD1. The results do not support generation of nitrotyrosine being the
      predominant lethal gain of function conferred by mutations in SOD1.

PMID- 11338200
TI  - Cerebral ischemia/reperfusion injury in rat brain: effects of naloxone.
AB  - The pathogenesis of cerebral ischemia/reperfusion (I/R) involves
      cytokine/chemokine production, inflammatory cell influx, astrogliosis,
      cytoskeletal protein degradation and breakdown of the blood-brain barrier. (-)
      Naloxone is able to reduce infarct volume and has been used as a therapeutic
      agent for cerebral I/R injuries. However, its effects on the mentioned
      pathophysiologic changes have scarcely been addressed. Cerebral I/R was produced
      by occluding and opening bilateral common carotid artery and unilateral middle
      cerebral artery in Sprague-Dawley rats. After cerebral I/R, the degradation of
      neuronal microtubule-associated protein-2 (MAP-2) was strongly associated with
      astrogliosis, inflammatory cell infiltration, cytokine/chemokine overproduction,
      and matrix metalloproteinase-9 activation. (-)-Naloxone pretreatment suppresses
      post-ischemic activation and preserves more MAP-2 protein. Therefore, (-)
      naloxone administration might be an effective therapeutic intervention for
      reducing ischemic injuries.

PMID- 11338201
TI  - Neural correlates of verbal memory encoding during semantic and structural
      processing tasks.
AB  - Eighteen participants were imaged using fMRI to explore whether brain regions
      predicting successful verbal memory encoding during semantic decisions would
      continue to predict encoding during structural (non-semantic) decisions.
      Consistent with prior studies, left inferior frontal and fusiform regions were
      more active during semantic than structural decisions, and activity was greater
      for remembered than forgotten words during semantic decisions. Critically,
      structural decisions yielded significantly greater activity for remembered than
      forgotten words in these regions providing evidence that a common frontal
      temporal network supports verbal memory encoding irrespective of orienting task.
      Further analysis revealed activity associated with successful encoding in the
      right precentral gyrus, suggesting other regions may also play a role in verbal
      encoding during non-semantic processing.

PMID- 11338202
TI  - Diffuse neurofibrillary tangles with calcification (a form of dementia): X-ray
      spectrometric evidence of lead accumulation in calcified regions.
AB  - Diffuse neurofibrillary tangles with calcification (DNTC) is a form of slowly
      progressive dementia in which no senile plaques are observed. The calcification
      is one of the most characteristic features of DNTC. We examined the elemental
      content of certain mineral deposits (lead, magnesium, phosphorus, calcium, iron,
      copper and zinc) in the calcified and non-calcified regions of eight cases of
      DNTC, five cases of Alzheimer's disease (AD) and in eight non-demented elderly
      controls. The study was performed using a combination of scanning electron
      microscopy and X-ray spectrometry on 10% formalin-fixed brain tissue. A marked
      abundance of calcium and phosphorus was observed in the calcified regions of DNTC
      and non-DNTC brains. Although no lead was observed in the non-calcified regions
      of DNTC and in non-DNTC brains, traces of lead were detected exclusively in the
      calcified regions of DNTC brains. The implications and possible significance of
      the lead accumulation in DNTC brains are discussed.

PMID- 11338203
TI  - Corticosterone-aggravated ischemic neuronal damage in vitro is relieved by
      vanadate.
AB  - Preischemic hyperglycemia-aggravated neuronal damage has been postulated to occur
      via enhanced lactic acidosis. We have hypothesized that preischemic glucose
      loading induces a short-lived elevation in glucocorticoid release which, when
      combined with ischemia, aggravates the postischemic outcome. This study tested
      this hypothesis in rat hippocampal slices exposed to 4 min in vitro ischemia of
      which 58% exhibited recovery of neuronal function. However, when corticosterone
      (CT) was present during ischemia, the recovery of neuronal function decreased in
      a concentration-dependent manner. At 5 microM, CT reduced the recovery rate to
      40% while only 10% of slices recovered when exposed to 20 microM CT. Insulin
      could not block the effect of CT; however, vanadate improved the postischemic
      recovery of CT-treated (20 microM) slices to 43%. These results indicate that
      acute, short exposure to CT can significantly exacerbate postischemic outcome and
      that vanadate can antagonize CT action.

PMID- 11338204
TI  - Conversion of brain apolipoprotein E to an insoluble form in a mouse model of
      Alzheimer disease.
AB  - A beta deposition in the APPV717F transgenic model of Alzheimer's pathology
      involves apolipoprotein E (apoE). We measured soluble and insoluble apoE in brain
      region extracts at an early and late stage of plaque development. The apoE levels
      in the insoluble fraction were greatly elevated in the hippocampus and cortex of
      aged transgenic animals but were unchanged in wild type or young APPV717F
      animals. Soluble apoE levels were unaltered. A beta levels were also measured and
      a positive correlation between apoE and A beta in the insoluble fraction was
      observed. ApoE transcription was increased approximately 3-fold in the
      hippocampus of 17-month-old APPV717F mice, suggesting a region-specific
      upregulation of apoE transcription in the brains of APPV717F mice to compensate
      for apoE sequestered with fibrillar A beta.

PMID- 11338205
TI  - Regeneration of a transected peripheral nerve by transplantation of spinal cord
      encapsulated in a vein.
AB  - The objective was to investigate the regeneration of a transected peripheral
      nerve after transplantation of fragmented embryonic (E14-15) spinal cord cells
      which were encapsulated within a vein cavity. After 3 months transplantation,
      axonal regeneration was observed by staining with HE and antibody to
      neurofilament subtypes in six of 10 rats. In all six animals compound muscle
      action potentials to electrical stimulation could be recorded and indicated
      incomplete reinnervation of the fibular and tibial nerve, respectively. A chronic
      inflammation process around the transplant and a negative result of staining
      neurofilaments within the vein cavity and the transected nerve were found in
      animals lacking electrophysiological response to stimulation.

PMID- 11338206
TI  - Melatonin acts as antioxidant and pro-oxidant in an organotypic slice culture
      model of Alzheimer's disease.
AB  - An organotypic mouse brain slice culture system of Alzheimer's disease (AD) under
      low oxygen partial pressures was developed to determine the antioxidant
      properties of the pineal hormone melatonin in vitro. Assays for biochemical
      markers of oxidative stress including redox active iron assay, heme-oxygenase-1
      and 8-hydroxyguanosine inmunoreactivity were performed along with morphological
      analysis for stressed tissue following amyloid-beta (A beta) 1-40 insult.
      Melatonin (100 microM) significantly reduced the appearance of condensed
      chromatin, redox active iron, heme-oxygenase-1 induction and 8-hydroxyguanosine
      immunoreactivity caused by 50 microM A beta. Melatonin also prevented A beta
      induced morphological signs of oxidative stress in tissue ultrastructure,
      including edema and dark degenerating profiles as visualized under electron
      microscope. At elevated concentrations (1 mM), melatonin induced redox active
      iron and heme-oxgenase-1 immunoreactivity. Thus, while melatonin may be a
      potential therapeutic agent in the prevention of oxidative stress associated with
      A beta and AD, it can also induce markers of oxidative stress at millimolar
      concentrations.

PMID- 11338207
TI  - Time course of short-term and long-term orexigenic effects of Agouti-related
      protein (86-132).
AB  - Agouti-related protein (AGRP) is a newly identified orexigenic peptide that acts
      as an endogenous antagonist of melanocortin receptors MC3 and MC4. The present
      study examined the time course of the orexigenic effects of synthetic AGRP (86
      132). Intracerebroventricular infusion of 0.1 nmol AGRP (86-132) increased food
      intake by 450 +/- 81% at 2 h post-injection. A second increase in non-cumulative
      food intake (512 +/- 135%) was observed at 6 h post-injection. Following a single
      dose of AGRP (86-132) (0.1 nmol) the increased food intake was sustained for 6
      days, occurring in the light cycle of the first 2 days and subsequently switching
      to the dark cycle of the last 4 days. These time course profiles indicate the
      complexity of the mechanisms involved in AGRP-induced feeding.

PMID- 11338208
TI  - Immunocytochemical localization of metabotropic glutamate receptor type 1 alpha
      and tubulin in rat brain.
AB  - The distribution of mGlu1 alpha receptor and tubulin was immunocytochemically
      examined in the rat cerebellar cortex and primary rat cortical neurons at both
      immunofluorescence and electron microscopic level. In cryosections from rat
      cerebellar cortex mGlu1 alpha receptor immunoreactivity was expressed in cell
      bodies and dendrites of Purkinje and basket cells of the cerebellar molecular
      layer. Tubulin immunoreactivity was concentrated in the dendritic tree of the
      cerebellar molecular layer, as well as in the granule cell layer. In primary rat
      cortical neurons, both proteins colocalized throughout the proximal and distal
      dendrites of these cells. At the electron microscopic level, the receptor was
      present in dendritic shafts and dendritic spines of Purkinje cells at
      perisynaptic sites of asymmetrical synapses. Immunoreactivity corresponding to
      tubulin was associated with the plasma membrane of dendritic shafts of Purkinje
      cells, as well as throughout its cytoplasm as part of the cytoskeletal
      components. Interestingly, double labeling for both proteins reveals an
      association of tubulin with mGlu1 alpha receptor at the plasma membrane level of
      dendritic shafts of Purkinje cells. This suggests that tubulin interacts with
      mGlu1 alpha receptor and may be involved in the anchoring of the receptor to the
      plasma membrane.

PMID- 11338209
TI  - Insulin-like growth factor I potentiates kainate receptors through a
      phosphatidylinositol 3-kinase dependent pathway.
AB  - Neurotrophic factors modulate synaptic plasticity through mechanisms that include
      regulation of membrane ion channels and neurotransmitter receptors. Recently, it
      was shown that insulin-like growth factor I (IGF-I) induces depression of AMPA
      mediated currents without affecting NMDA-receptor function in neurons. We now
      report that IGF-I markedly potentiates the kainate-preferring ionotropic
      glutamate receptor in young cerebellar granule neurons expressing functional
      kainate-, but not AMPA-mediated currents. Potentiation of kainate responses by
      IGF-I is blocked by wortmannin, a phosphatidylinositol 3-kinase (P13K) inhibitor,
      indicating a role for this kinase in the effect of IGF-I. These results reinforce
      the notion that modulation of ionotropic glutamate receptors are involved in the
      regulatory actions of IGF-I on neuronal plasticity.

PMID- 11338210
TI  - Enhanced late components of AEFs associated with the temporal lobe lesions.
AB  - We recorded auditory evoked magnetic fields (AEFs) by presenting pure tone bursts
      once every 4000 ms in 11 patients with a brain lesion in or in the vicinity of
      the auditory cortex. AEFs on the damaged side revealed several enhanced
      deflections in late-latency AEFs (slow AEFs), peaking at approximately 320 (DI),
      1030 (D2) and 1600 (D3) ms post-stimulus in eight patients. All the dipoles of
      slow AEFs were concentrated in the superior temporal regions which were not
      involved by brain lesions. D1, D2 and D3 dipoles were uniformly upward, downward
      and upward, respectively. The dipole moment varied from 12 to 122 nAm and had no
      consistent relationship with latency. This is the first report describing slow
      AEFs in cases with temporal lobe lesions.

PMID- 11338211
TI  - NMDA receptor subunits are phosphorylated by activation of neurotrophin receptors
      in PSD of rat spinal cord.
AB  - We have investigated the distribution of NMDA and neurotrophin receptor systems
      and their reciprocal interactions in post-synaptic densities (PSD) purified from
      spinal cord. NMDA receptor subunits, trkA and trkB, but not trkC, were present in
      spinal cord PSD. The incubation of PSD with BDNF and NGF induced the
      phosphorylation of NR2A and B subunits. This phosphorylation was counteracted by
      antibodies directed against the catalytic domain of trkA and trkB receptors and
      by genistein. These results suggest the existence of a previously unexplored
      cross-talk between neurotrophins and NMDA receptors in rat spinal cord neurons.

PMID- 11338212
TI  - c-Fos expression in rat brain after repetitive transcranial magnetic stimulation.
AB  - We investigated neuronal response to repetitive transcranial magnetic stimulation
      (rTMS) and electroconvulsive shock (ECS) in terms of c-Fos expression. In rats at
      postnatal day 49, six rTMS sessions induced widespread nuclear c-Fos-like
      immunoreactivity in frontal cortex, lateral orbital cortex, striatum, lateral
      septal nucleus, piriform cortex, dentate gyrus, Ammon's horn, cingulate cortex,
      parietal cortex, thalamus, occipital cortex, and amygdala; this reactivity was
      greater than with two sessions of rTMS or sham rTMS. ECS produced even stronger c
      Fos expression than six sessions of rTMS in all regions except thalamus (no
      difference) and striatum (stronger with rTMS). Thus, functional modification of
      neuroanatomic substrates as demonstrated by c-Fos expression may partially differ
      between rTMS and ECS.

PMID- 11338213
TI  - Subthreshold membrane oscillations underlying integer multiples firing from
      injured sensory neurons.
AB  - Integer multiples firing (IMF), a special temporal pattern of firing, was
      recently observed in spontaneous discharge from injured dorsal root ganglion
      (DRG) neurons. To investigate the mechanism underlying IMF, the injured DRG
      neurons of rat were recorded intracellulary. Of 64 recorded A-neurons discharging
      spontaneously, eight fired spikes in the IMF pattern. Interspike interval (ISI)
      time series of IMF showed a structure of distinct bands on scatter map. Regular
      subthreshold membrane oscillations (SMOs) with relatively stable amplitude and
      frequency were observed on all eight IMF neurons. IMF could be induced from the
      neurons in periodic firing by local application of tetrodotoxin (TTX), a Na+
      channel antagonist. During this process, the amplitude of SMOs varied markedly.
      Some SMOs were below action potential threshold so that they did not trigger
      spikes. Nor did some SMOs, though their amplitude were obviously beyond the
      threshold measured from nearby spikes. The results indicate that regular SMOs
      existent in injured DRG A-neurons underlie IMF, and the TTX-induced
      transformation of firing pattern from periodic to integer multiples may occur in
      two ways: decreasing the amplitude of SMOs and/or elevating action potential
      threshold.

PMID- 11338214
TI  - Recent advances in the hearing assessment of children.
AB  - The remarkable specificity and sensitivity of otoacoustic emissions (OAEs) in
      identifying cochlear dysfunction, and the speed and objectivity with which the
      test can be conducted has made the OAE procedure the 'standard-of-care' in
      pediatric audiology assessment. Together with the auditory brainstem responses
      (ABRs), the OAE procedure not only separates sensory from neural impairment, but
      also facilitates early audiologic diagnosis and management. This article
      describes some unique applications of the OAE procedure in the diagnosis,
      monitoring and treatment of auditory dysfunction.

PMID- 11338215
TI  - Long-term nutritional effects of ICDS.
AB  - Nutritional status of 1243 children (636 boys and 607 girls) in the age group of
      7-13 years was assessed in relation to utilisation of Integrated Child
      Development Services (ICDS) during their childhood. All the houses in every 10th
      Anganwadi selected by systematic random sampling were surveyed in the ICDS
      project, Nand Nagri in East Delhi. Information regarding utilisation of ICDS
      facilities, sociodemographic details, general awareness etc. was collected by
      interview technique and anthropometric and clinical examination of every child
      was done and Anganwadi attendance score was calculated for each child. It was
      found that most of the children were non-beneficiaries (59.1%). On univariate
      analysis Anganwadi attendance score, age, sex of the child and education status
      of the father showed statistically significant association (p < 0.005) with
      malnutrition. On Multiple logistic regression analysis higher age (OR 1.4155 for
      grade 1 malnutrition and 1.6913 for grade 4 malnutrition) and being female (OR
      1.5214 for Grade 4 malnutrition) remained significant risk factors for
      development of malnutrition for all grades. Anganwadi attendance score did not
      show any statistically significant association for decreasing the risk of getting
      malnourished for any grades of malnutrition in 7-13 years age group. There is
      special need to take special care for girls as well as to continue the special
      nutrition care even at an higher age. More in depth studies are needed so as to
      formulate effective nutritional policies for children.

PMID- 11338216
TI  - Tumour necrosis factors in childhood asthma.
AB  - Tumour necrosis factor-alpha (TNF alpha) and TNF beta levels in serum were
      measured by enzyme immunoassays in 64 Libyan children (age: 1-12 years, sex: 39
      males, 25 females) with mild to moderately severe asthma (Group A). Among these
      patients, 35 had active disease (AA) and 29 had inactive disease (NA). According
      to age range, 20, 21 and 23 patients were between 1-3 years (A1), > 3-5 years
      (A2) and > 5-12 years (A3) respectively. A1 had 9 and 11 patients with active
      (AA1) and inactive (NA1) disease; A2 had 10 and 11 patients with active (AA2) and
      inactive (NA2) disease; A3 had 16 and 7 patients with active (AA3) and inactive
      (NA3) disease respectively. Age-matched comparisons was made with 57 healthy
      children (age: 1-12 years; sex: 30 males, 27 females) (Group B). Among the
      controls, 15, 19 and 23 children were between 1-3 years (B1), > 3-5 years (B2)
      and > 5-12 years (B3) respectively. It was observed that serum mean TNF alpha
      level was significantly higher in patients, while TNF beta levels was normal (A
      vs B-TNF alpha P < 0.001, TNF beta: P > 0.1). The TNF alpha level was elevated
      significantly in active disease, while it was normal in inactive disease (AA, NA,
      B: P = 0.0001; AA vs NA; P < 0.0001; NA vs B: P > 0.05) and TNF beta levels were
      normal in both groups (AA, NA, B: P = 0.25). Further, TNF alpha levels were
      significantly higher in all age ranges but in patients with active disease only
      (AA1, NA1, B: P = 0.0008; AA2, NA2, B: P = 0.0003; AA3, NA3, B: P = 0.0396). TNF
      alpha may therefore be involved in the pathophysiology of asthma possibly through
      various proinflammatory mechanisms.

PMID- 11338217
TI  - Diabetes in adolescent patients: diagnostic dilemmas.
AB  - The classification of diabetes mellitus by types (1 or 2), or by age of onset
      (juvenile or adult), helps to clarify many aspects of pathophysiology, prognosis,
      and therapy. However, less-commonly encountered patients, presenting in childhood
      or adolescence, may not fit neatly into one or the other group. These include
      teenagers who present with new-onset diabetes with ketoacidosis, but who are
      later able to be managed permanently as type 2 patients. Other adolescent
      patients present with only minimal glucose intolerance, then proceed to develop
      type 1 diabetes, with evidence of autoimmune etiology, after a variable number of
      years. Four patients are presented to illustrate these diagnostic dilemmas.

PMID- 11338218
TI  - Prevalence of goitre in school-going children in Jabalpur.
AB  - To determine the prevalence of goitre in school going children in Jabalpur city
      and critically evaluate clinical, biochemical and hormonal profile of goitrous
      children, 1205 children (800 boys and 405 girls) between 6 to 15 years of age
      were enrolled from 6 different schools located within the Jabalpur city limits.
      Conducting a Cross-sectional survey relevant family variables, eating habits
      (including type of salt used), anthropometry and general physical details were
      recorded in a pre-designed proforma. Thyroid gland was examined and graded as per
      standard technique. Spot urinary iodine excretion (UIE) of all goitrous children
      (n = 26) and randomly selected age and sex matched normal non-goitrous children
      (n = 63) was determined by dry-ashing method. Thyroid hormone profile of goitrous
      children was assessed by radio-immuno-assay. Student's t-test, z-test and
      proportionate test were employed to evaluate the statistical significance of the
      observations. It has been drawn a result that there was low prevalence of goitre
      in school going children of Jabalpur city. (2.4%, 26/1205). Girls had a higher
      prevalence (3.2%) than boys (1.6%), however the difference was statistically not
      insignificant. All goitrous children had small goitre (Grade I) 88.76% children
      had spot UIE > 100 mcg/l with as many as 13.4% having spot UIE > 150 mcg/l. No
      child had spot UIE < mcg/l. 11.23% of children had spot UIE of < 100 mcg/l with
      higher proportion of goitrous children (7/26, 26.92%) than the age matched, non
      goitrous controls (3/63, 4.76%). The mean UIE of goitrous children was 109.6 +/-
      22.1 mcg/l (range 80-150 mcg/l) and that of control children was 122.9 +/- 17.0
      mcg/l (range 90-150 mcg/l). Thyroid hormone profile of goitrous children was in
      euthyroid range. Salt iodine content could not be done due to non-availability of
      kit. Jabalpur city is not endemic for iodine deficiency both by clinical as well
      biochemical criteria. The observed goitre cases are of sporadic variety.

PMID- 11338219
TI  - Vitamin K deficiency in diarrhoea.
AB  - The study was undertaken to determine the frequency of occurrence of vitamin K
      deficiency in infants with diarrhoeal illness. Infants were categorized into four
      groups as follows: A(acute diarrhoea), B(protracted diarrhoea) C(intractable
      diarrhoea) and D(healthy controls). Screening coagulation tests, PT and PTTK
      along with estimation of functional activity and total antigenic levels of
      prothrombin were performed. The ratio of functional to total prothrombin was
      calculated. PT was prolonged in 30% (24/75) of all infants with diarrhoea as
      compared to controls where the abnormality was observed in 11.1% infants (2/18).
      The ratio of functional to total prothrombin was significantly lower in infants
      with diarrhoea, the mean +/- SD values being 0.65 +/- 0.41 vs 1.1 +/- 0.26. This
      difference was statistically highly significant (p < 0.001). Low ratio was
      observed in 57.3% (43/75) infants with diarrhoea. Thus functional to total
      prothrombin ratio identified approximately twice as many diarrhoeal infants with
      vitamin K deficiency as compared to PT alone. There was no significant
      correlation with breast feeding as the only mode of diet, or the prior
      administration of antibiotics in infants with diarrhoea. The inherent
      malabsorptive state in diarrhoea may be a major contributory factor.

PMID- 11338220
TI  - Pulmonary function tests in beta thalassemia.
AB  - To study pulmonary function tests (PFT) in multiple transfusion recipient
      thalassemics, PFTs were done for 30 thalassemics and 20 matched controls.
      Confirmed cases of thalassemia on regular transfusion therapy were the subject of
      study. Apart from history and physical examination of the thalassemics, serum
      ferritin estimation and spirometry were done. Parameters studied included lung
      volumes--functional residual capacity (FRC), forced vital capacity (FVC),
      residual volume (RV) and total lung capacity (TLC); and flow rates--forced
      expiratory volume in one second (FEV1), forced expiratory volume in 1
      second/forced vital capacity (FEV1/FVC), peak expiratory flow 25-75 (PEF 25-75%)
      and peak expiratory flow rate (PEFR). Single breath carbon monoxide diffusing
      capacity (DLco) and arterial blood gas (ABG) were also analysed. The mean height
      and weight of thalassemics were below that of age matched controls. A restrictive
      abnormality in PFT was found in 86.6% cases. These patients were found to have a
      decrease in all the lung volumes namely FVC, FRC, RV and TLC with a proportional
      decrease in the flow rates, FEV1, PEF 25-75% and PEF with a normal (> 0.75)
      FEV1/FVC ratio. DLco was decreased in all the patients with restrictive lung
      disease and fall in DLco showed a good correlation (r = 0.7, P < .001) with the
      severity of restrictive disease suggesting that some intrapulmonary pathology is
      likely to be responsible for the restrictive pattern. None of the cases had an
      obstructive or mixed pattern of pulmonary dysfunction. No correlation was found
      between severity of restrictive disease and the serum ferritin levels. A negative
      correlation with degree of hepatosplenomegaly was found. No correlation was found
      between severity of the defect and age, number of blood transfusions received and
      hemoglobin at the time of doing the test. To conclude, restrictive lung disease
      is the predominant abnormality in multi-transfused thalassemics, which is
      probably due to pulmonary parenchymal pathology. The abnormality of PFTs is not
      directly related to iron overload.

PMID- 11338221
TI  - Measurement of laryngeal dimensions in neonates.
AB  - Intimate knowledge of laryngeal anatomy and various laryngeal dimensions is
      crucial for successful airway management. Selection of a proper endotracheal tube
      is also a critical factor. Subglottic dimension is the most important measurement
      of larynx because of it being the narrowest part of the infant larynx. Data about
      various infantile laryngeal dimensions in Indian population is sparse. In this
      article, we present various laryngeal dimensions using 30 infantile laryngeal
      autopsy specimens and review of literature.

PMID- 11338222
TI  - Pediatric intensive care--pediatrics for the new millennium.

PMID- 11338223
TI  - Acute respiratory failure and oxygen therapy.
AB  - Acute Respiratory Failure (ARF) results in an inability to maintain gas exchange
      at a rate commensurate with the demands of the body and results in hypoxemia
      and/or hypercarbia, the mechanisms of which may be different. Hypoxemia commonly
      occurs due to Ventilation Perfusion (V/Q) mismatching, intrapulmonary shunt,
      diffusion defect or hypoventilation. Hypercarpnic respiratory failure may also be
      multifactorial but is usually due to inhibited central respiratory drive or
      inefficient respiratory muscle pump. Hypercapnia may occur in upper and lower
      airways obstruction, respiratory muscle fatigue and occasionally due to excess
      CO2 production (burns and excessive glucose administration). Issues in management
      centre around assessment of severity, determining the need for intervention,
      establishing diagnosis and etiology and institution of specific treatment.
      Diagnosis of respiratory failure may be made clinically and confirmed by blood
      gas analysis. Calculation of oxygenation indices will delineate extent of
      hypoxemia. When evaluating a child with respiratory failure, one should be aware
      that a child with prominent respiratory symptoms may have non-respiratory disease
      (i.e. metabolic acidosis, DKA) and conversely, advanced respiratory failure may
      be present in a child with no respiratory distress (central hypoventilation
      secondary to drugs, infection) careful assessment of history, complete physical
      examination and evaluation of lab parameters may clarify the diagnosis. Serial
      assessment of sensorium, respiratory symptoms, ABG and response to treatment will
      provide valuable clues to determine the need for intervention. Oxygen, like any
      drug, must be administered in a prescribed dose, only when indicated with the
      potential risks borne in mind. A variety of oxygen delivery devices are
      available; which ever device is used, the resulting FiO2 and devisable end points
      must be clearly determined. Hazards of oxygen therapy range from retinal damage
      in premature infants, damage to the alveolar capillary membrane with resultant
      hypoxemia) atelectasis and decreased mucociliary activity.

PMID- 11338225
TI  - Post-neonatal tetanus: issues in intensive care management.
AB  - Tetanus is an acute neurological disease characterized by muscle rigidity and
      spasms, autonomic dysfunction and in severe forms requires respiratory and
      hemodynamic support. Though it is entirely preventable by immunization, it still
      occurs in developing countries causing significant morbidity and mortality.
      Intensive care management of tetanus is fraught with problems of ventilator
      associated pneumonia, nosocomial sepsis and a variety of other complications.
      Various treatment protocols have been tried in managing diverse manifestations of
      severe tetanus but the consensus is yet to emerge. In this review we have
      discussed the pathophysiology, clinical features and management controversies and
      suggest on basis of our experience use of high dose diazepam (20-120 mg/kg/day)
      and vecuronium with mechanical ventilation if required for control of spasms, and
      early detection of autonomic dysfunction and use of propranolol, in our
      circumstances.

PMID- 11338224
TI  - Neurocritical care and traumatic brain injury.
AB  - The majority of severely head injured children will not require neurosurgery. For
      the pediatrician, the central question must be whether medical interventions are
      effective in limiting morbidity and treating the problem of cerebral oedema.
      However, in order to address this issue we need to give some thought to the
      system of care in which we practice, how we assess the severity of brain injury
      and whether, in regard to pathophysiology, responses in children are
      significantly different from those seen in adults. In this regard, this review
      highlights some of the recent pediatric neurocritical care literature and
      provides, for the clinician, a framework on which to base ones medical management
      of severe traumatic brain injury occurring in childhood.

PMID- 11338226
TI  - Child with absent vital signs.
AB  - The outcome of cardiopulmonary resuscitation in the child with absent vital signs
      is dismal. Best outcomes therefore should rely on early recognition and
      aggressive management of critical illness to interrupt deterioration to
      cardiorespiratory arrest. Moreover, resuscitation entails a spectrum of care
      starting with cardiopulmonary resuscitation at the site of injury through
      critical care and post resuscitation rehabilitation. The resources required to
      provide this level of care is not available in many parts of the world.
      Therefore, resuscitation skills should be taught to caregivers at a level which
      is congruent to their role in the continuum of care and the use of aggressive
      resuscitation needs to be tailored based on geography, risk to medical personnel,
      preservation of resources, transplantation issues and expected outcomes. In some
      cases, the most prudent decision may be not to attempt resuscitation of the child
      with absent vital signs.

PMID- 11338227
TI  - Pseudohypoparathyroidism in a mother and son: phenotypic variability and
      associated disorder.
AB  - A 2-month-old infant with clinical features of hypothyroidism presented with
      hypocalcemic seizures. The maternal phenotypic features aroused the suspicion of
      pseudohypoparathyroidism which was confirmed in both by biochemical and
      endocrinological investigations. Though the child had clinical and radiological
      features to suggest hypothyroidism he had normal free thyroxine and only slightly
      elevated thyroid stimulating hormone levels. Special note is made of the intra
      and interpatient variability of this rare inherited disorder.

PMID- 11338228
TI  - Neonatal parotitis.
AB  - Neonatal parotitis is a rare condition. Infection of the parotid glad is more
      common than that of the submandibular glad. Dehydration is the most important
      predisposing factor for this. Most common organism responsible for this condition
      is Staphylococcus aureus. Untreated condition can lead to various complications.

PMID- 11338229
TI  - Unusually severe ABO hemolytic disease of newborn.
AB  - ABO-hemolytic disease of newborn (ABO-HDN) is a common cause of neonatal
      hyperbilirubinemia. Most of the cases are however mild. We describe a neonate
      with ABO-HDN with unusually severe course.

PMID- 11338230
TI  - Hypocalcemic heart failure masquerading as dilated cardiomyopathy.
AB  - Hypocalcemia is a rare, but reversible, cause of congestive heart failure. We
      report a 4-month-old boy diagnosed as dilated cardiomyopathy who had prolonged
      QoTc with low blood levels of calcium, normal phosphate, elevated alkaline
      phosphatase and findings suggestive of rickets. In view of non response to
      calcium and vitamin D3, a possible diagnosis of VDDR I (Vitamin D-dependent
      rickets) was made and he was treated with calcium and calcitriol. The serum
      calcium levels normalised within 10 days, along with resolution of the signs and
      symptoms of heart failure, near normal left ventricular function and
      normalisation of QoTc. Pediatricians should be aware of the association of
      hypocalcemia with cardiac dysfunction and should keep it as a possible reversible
      cause of heart failure in children.

PMID- 11338231
TI  - Kawasaki disease--atypical presentation.
AB  - Kawasaki disease, an acute systemic vasculitis of unknown etiology, is the
      leading cause of acquired heart disease in children in many parts of the world.
      It predominantly affects children under 5 years of age and is diagnosed
      clinically by the presence of characteristic clinical signs. Atypical patients,
      often younger than 1 year of age, manifest few early signs, usually have an
      incorrect admitting diagnosis and suffer from high morbidity and mortality. We
      report the presentation, clinical course and follow-up of a 3-month-old infant
      with atypical Kawasaki disease.

PMID- 11338232
TI  - Intestinal perforation due to polyarteritis nodosa.

PMID- 11338233
TI  - Was I doing my duty--or ratting on a colleague?

PMID- 11338234
TI  - Larry I. Wolk, MD. Keeping kids who need care from falling through the cracks.

PMID- 11338236
TI  - This doctor works for a song.

PMID- 11338235
TI  - Stay young, I told myself--and took up the cello.

PMID- 11338237
TI  - When a patient might become violent.

PMID- 11338238
TI  - Who wants to be a millionaire inventor?

PMID- 11338239
TI  - Is your system in neutral when it should be in drive?

PMID- 11338240
TI  - Keep your practice alive when the computer goes dead.

PMID- 11338241
TI  - Unconscious in the ICU: been there, done that!

PMID- 11338242
TI  - Home care: your best ally against refractory illness.

PMID- 11338243
TI  - How to get help for your troubled patients.

PMID- 11338244
TI  - Why is it so hard to report a problem doctor?

PMID- 11338245
TI  - A friend leaves for Washington.

PMID- 11338246
TI  - HIV testing.

PMID- 11338247
TI  - Walter J. Kahn, MD. Looking back, looking forward.

PMID- 11338248
TI  - Automated external defibrillators and sudden cardiac arrest.
AB  - In April 1998, R.R., aged 72 (a man with no prior history of cardiac disease),
      was leaving his house with two friends to play golf when he suddenly collapsed.
      One friend initiated CPR, and the other called 911 on his cellular phone. A
      Chatham police squad arrived within three minutes; the police "first responder"
      applied a portable automated external defibrillator (AED) to the unresponsive
      patient. The AED instructed the first responder to push the shock button. Pulse
      and blood pressure were immediately restored, and the patient was brought to the
      Overlook Hospital Emergency Room. The patient subsequently awakened, had a
      cardiac catheterization revealing severe three-vessel coronary artery disease,
      and then underwent successful coronary artery bypass surgery. Two and a half
      years later he remained asymptomatic and was seen in the office of his
      cardiologist for a routine semiannual exam. Later that same day he was scheduled
      to play golf with the same two friends who had previously saved his life.

PMID- 11338249
TI  - The most dreaded complication of labor. The history of eclampsia treatment in New
      Jersey.
AB  - Guided by articles and case reports in New Jersey's medical journals, 19th
      century practitioners managed eclampsia in accordance with evolving theories and
      practices. Early 20th-century advances gradually improved maternal outcomes.

PMID- 11338250
TI  - [New treatments for cardiac insufficiency].

PMID- 11338252
TI  - [Primary angioplasty associated with systemic coronary stenting in acute
      myocardial infarction. Results at the end of the hospitalization period and at 24
      months].
AB  - A series of 149 consecutive patients admitted for myocardial infarction
      (excluding cardiogenic shock), dilated and systematically stented in the acute
      phase before the 12th hour and followed up for a period from 30 days to 2 years,
      was studied. The criteria of follow-up were: number of asymptomatic patients,
      deaths, reinfarction, residual ischaemia, cardiac failure, angioplasty or bypass
      surgery. On admission, 40.9% of the infarcts were anterior, 44.3% inferior and
      14.8% lateral. One hundred and eighty-three stents with a diameter of over 3 mm
      were inserted. The angioplasty success rate was 98.6%. During the hospital
      period, 90.6% of patients were asymptomatic. 4.7% had recurrent infarction, 4%
      had cardiac failure, 0.7% had residual ischaemia, and there were 0.7% of cardiac
      deaths. The survival rate was 97.2% at 2 years: 69.8% of patients were totally
      asymptomatic: the cumulative major cardiac event rate (death, reinfarction,
      angioplasties or bypass graft) was 25.9% and the reoperation rate on the culprit
      vessel was 20.1%. These results show the short and long-term value of angioplasty
      associated with coronary stenting over other techniques in the acute phase of
      infarction based on the criteria studied. The long-term results of larger
      randomised studies using glycoprotein inhibitors (Gp IIb IIIa) associated with
      angioplasty and stenting are expected for validating the use of these products.

PMID- 11338251
TI  - [Autologous skeletal myoblast transplantation for cardiac insufficiency. First
      clinical case].
AB  - The authors report the first intramyocardial transplantation of autologous
      skeletal myoblasts in a patient with severe ischaemic cardiac failure. The
      encouraging result after eight months' follow-up underlines the potential of this
      new approach.

PMID- 11338253
TI  - [Dual chamber rate responsive pacing and chronotropic insufficiency. Comparison
      of double and respiratory sensors].
AB  - Late responsive DDD pacemakers are the most technically advanced devices
      presently available. These pacemakers are particularly useful in patients with
      chronotropic insufficiency when the sinus node is incapable of accelerating
      during exercise. The latest pacemakers have two sensors to reproduce optimal
      physiological sinus acceleration. The aim of this study was to analyse the
      performances of a new rate responsive pacemaker with a double activity and
      respiratory sensor, the interaction of which is automatically controlled by a
      sophisticated algorithm, in 12 patients (8 men and 4 women) with a mean age of 75
      +/- 7 years. Analysis was based on the performance of the sensors used singly or
      in association: during three exercise stress tests with measurement of the VO2
      max; during everyday activities using the data archived by the pacemaker and the
      answers to a simplified questionnaire on quality of life. The results showed that
      during exercise stress testing with measurement of VO2 max, the best performances
      were obtained with the double sensor or the respiratory sensor compared with the
      activity sensor alone, suggesting that these two sensors are more effective in
      intense exercise. This tendency was also observed in the analysis of the memory
      bank of the pacemaker which showed that the total duration of the faster heart
      rates was greater with the two sensors. On the other hand, the quality of life
      was not significantly different, whichever sensor was studied. Longer scale
      trials are necessary to appreciate the real value of these new double sensor
      pacing devices and to identify the best indications for their usage.

PMID- 11338254
TI  - [Evaluation of a new stress echocardiography technique combining exercise and
      dobutamine in the detection of coronary disease].
AB  - Dobutamine stress echocardiography (DSE) and exercise stress echocardiography
      (ESE) are widely used for diagnosis of coronary artery disease. Each of these
      methods has limitations: secondary effects of Dobutamine, poor imaging quality,
      difficulty in attaining the maximal heart rate. The authors evaluated a test
      associating pedalling exercise at a constant low load (30-60 watts) with
      Dobutamine infusion (10-20-30-40 j/Kg/min +/- Atropine) (DES + E) in 42 patients
      referred for suspected coronary artery disease. All patients underwent coronary
      angiography on Day 1. There was significant coronary disease (> 50% stenosis) in
      19 of the 42 patients. Sensitivity, specificity, negative predictive value,
      positive predictive value and overall diagnosis value were respectively 84, 87,
      84, 87 and 86%. In the first 20 patients, the DES + E was compared directly with
      DES: There was only one undesirable side effect (hypertension) with DES + E
      compared with 5 with DES alone. The target heart rate was attained with lower
      doses of Dobutamine with DES + E (32.35 vs 39.42 j/Kg/min, p = 0.05). DES + E
      therefore seems to be a promising technique which is better tolerated than DES
      alone with very satisfactory diagnostic performances. However, these results
      require further confirmation in larger numbers of patients.

PMID- 11338256
TI  - [Antihypertensive therapy and improved life expectancy without cerebrovascular
      accident or coronary artery disease].
AB  - The absolute benefit from antihypertensive therapy increases with the baseline
      risk. However, age is a major determinant of cardiovascular risk, so it is
      important to express therapeutic efficacy with indices for which age is not a
      confounder. With this aim we explored the expected gain in life expectancy
      without cardiovascular events according to age at the initiation of the
      treatment. The treatment effect estimated from the INDANA meta-analysis, was
      applied to the cardiovascular risk of a French hypertensive population, simulated
      from national vital statistics. The gain in life expectancy was estimated from
      the area between survival curves without events. The treatment effect varied
      according three different hypotheses: increasing, decreasing or constant effect.
      When assuming a constant treatment effect, our results show a 29 month gain
      without stroke for a man who began his treatment at 40 years, and 15 months if
      hypertension is screened and treatment initiated at 75 years. The gains without
      coronary heart disease are respectively of 11 and 6 months. The variation of
      treatment effect over time could have a major impact on the treatment benefit.
      The gain in life expectancy without events is a relevant decision tool,
      completing usefully the absolute benefit, since it takes into account the
      influence of age.

PMID- 11338255
TI  - [Right ventricular dilatation and intraventricular septal motion after surgical
      closure of atrial septal defect].
AB  - The persistence of right ventricular dilatation and paradoxical interventricular
      septal motion are two echocardiographic abnormalities rarely reported after
      surgical closure of atrial septal defects. The aim of this study was to identify
      the predictive factors of these abnormalities in the long-term and to study their
      functional consequences. One hundred and two patients aged 18 +/- 14 years (range
      1-62 years) underwent closure of atrial septal defects. Thirty-five patients were
      under 10 years of age, 33 were 10 to 20 years of age and 34 were over 20. Fifty
      six patients were female. The rhythm was sinus in the great majority of cases
      (97%). Three patients, all over 40 years of age, were in atrial fibrillation.
      Before surgery, right ventricular dilatation was observed in 95 patients (91.2%),
      paradoxical septal wall motion in 93 patients (91.2%), the ratio of
      pulmonary/systemic output was 2.7 +/- 0.6 (range 1.7 to 7.4) and over 2 in 90% of
      patients: pulmonary systolic pressure was 32.3 +/- 12 mmHg and over 40 mmHg in 18
      patients (17.6%). Ninety-four patients were followed up regularly with a mean
      follow-up time of 5.5 +/- 3.6 years (1-14 years). The right ventricle remained
      dilated in 37 patients (39.4%) after surgery: the right ventricular dimension
      decreased from 36 +/- 1 to 27.8 +/- 6.2 mm (p = 0.001). The ratio of end
      diastolic right ventricular/left ventricular dimension also decreased from 1.07
      +/- 0.31 to 0.56 +/- 0.12 (p = 0.0001). Multivariate analysis identified two
      predictive factors of persistent right ventricular dilatation: age > 40 years (p
      = 0.009) and a pulmonary/systemic flow ratio > 3 (p = 0.03). Interventricular
      septal wall motion remained paradoxical in 21 patients (22%). Multivariate
      analysis identified two predictive factors of persistent paradoxical septal
      motion: age > 40 years (p = 0.02) and systolic pulmonary pressures > 40 mmHg (p =
      0.03). These abnormalities remained asymptomatic in all but two patients with
      persistent long-term hypertension and a residual atrial septal defect. The
      persistence of right ventricular dilatation and paradoxical septal motion was
      quite common, with older age at surgery, systolic pulmonary artery pressure > 40
      mmHg and a ratio of pulmonary/systemic blood flow > 3, being predisposing
      factors. These abnormalities were clinically asymptomatic when isolated.

PMID- 11338258
TI  - [Isolated pulmonary valve endocarditis: a case report].
AB  - The authors report the very rare case of isolated pulmonary valve endocarditis in
      the absence of classical predisposing factors and discuss the therapeutic
      approach. In the absence of large series, a maximum of information is developed
      from this new case, especially with respect to its unusual context.

PMID- 11338257
TI  - [Secondary effects of brachytherapy in the treatment of coronary restenosis].
AB  - Brachytherapy is proposed for the treatment or prevention of coronary restenosis
      with encouraging results, especially in intra-stent restenosis. The results of
      the first clinical studies show benefit, for example those of the American
      SCRIPPS trial with a 3 year follow-up. However, recent reports in the literature
      have described secondary effects associated with this technique: 1) stenoses
      occurring at the limits of the irradiated segments which are attributed to a
      proliferative effect of low doses on damaged tissue; 2) late occlusions at the
      irradiated site: their incidence is estimated at 9% at 6 months. The mechanisms
      of these thromboses are not understood but delayed re-endothelialisation probably
      plays a role; 3) finally, irradiation is associated with uncovered dissection
      probably related to delayed healing. Other long-term trials are necessary to
      provide a more complete assessment of the secondary effects of brachytherapy,
      especially with regards to their mechanisms, prevention and treatment.

PMID- 11338259
TI  - [Loffler's fibroblastic endocarditis. A report of a case complicating
      toxocarosis].
AB  - The authors report a case of Loffler's fibroblastic endocarditis complicating a
      toxocarosis infection. Parasitic infestation with toxocara canis is usually
      asymptomatic, but this was a very rare observation of cerebral involvement
      associated with symptomatic Loffler's endocarditis. This is an unusual form of
      restrictive cardiac disease constantly accompanied by prolonged
      hypereosinophilia. In addition to the classical signs of cardiac failure, an
      acute febrile illness imitating a connective tissue disease may be observed.
      Echocardiography helps diagnosis by showing endomyocardial fibrosis and adherent
      thrombosis at one or both ventricular apices. The management of cardiac failure
      should include, whenever possible, radical treatment of the hypereosinophilia. At
      an advanced stage, surgical endocardial decortication is the only means of
      improving symptoms and the prognosis of these patients.

PMID- 11338260
TI  - [First case of myocardial metastasis of an epidermoid tumor. Value of Doppler
      tissue imaging].
AB  - The authors report the first case of a poorly differentiated epidermoid
      oesophageal cancer with myocardial metastasis. The diagnosis of malignant
      invasion of the myocardium was made by transthoracic echocardiography with
      electrocardiographic changes of subepicardial ischaemia. The authors review the
      literature of metastasic cardiac disease after the study of this particular case
      and underline the value of Doppler tissue imaging for myocardial
      characterisation.

PMID- 11338261
TI  - [Cardiogenic shock complicating extensive infarction with ventricular septal
      defect. Circulatory assistance and heart transplantation].
AB  - A 47 year old man had a massive anterior myocardial infarction with cardiogenic
      shock with a left parasternal murmur. Coronary angiography showed occlusion of
      the left anterior descending artery for which angioplasty resulted in failure.
      There was antero-lateral-apical akinesia and a ventricular septal defect (VSD)
      with a left-right shunt (Qp/Qs = 1.54). Persistence and aggravation of
      haemodynamic instability led to intra-aortic balloon pumping with inotropic
      pharmacological support followed by biventricular assistance with a MEDOS device.
      Under transoesophageal echocardiographic monitoring, the outcome was marked over
      7 days by the progressive increase in the shunt volume of the VSD, a decrease of
      drainage and injection flow, progressive increase in spontaneous contrast echos
      followed by the presence of fibrin in the cardiac chambers and canulae, the
      presence of thrombus in the external ventricles, blockage of the right external
      valve which only opened after increasing the degree of anticoagulation, and,
      finally, cardiac tamponade which required drainage before the patient's state
      improved. On the 8th day, the patient being stable with a normal neurological
      status, the availability of a donor heart led to the decision to transplant,
      which was carried out without complications. This case poses the problem of
      cardiac assist devices and their daily monitoring, and then that of cardiac
      transplantation in this indication.

PMID- 11338262
TI  - [Left ventricular aneurysm revealed by a ventricular tachycardia].

PMID- 11338263
TI  - [The histopathologic picture after chemical eye injury and the role of limbal
      stem cells].
AB  - The aim of this experimental study was to evaluate the role of limbal stem cells
      on corneal wound healing. The experimental objects were New Zealand white
      rabbits. Damage to the cornea was caused by 2.5 N NaOH solution for 50 sec. and
      was subsequently washed out by saline solution. The rabbits were euthanased 24
      hours after alkaly burn and the tissue was fixated in 10% formalin. The samples
      were embedded in paraffin and stained with haematoxilin and eosin. The specimen
      showed focal inflammatory reaction with the presence of macrophages an round-
      nucleated cells in the limbal area.

PMID- 11338264
TI  - [Treatment of paralysis of cranial nerve VI: evaluation of the Hummelsheim method
      of transposition surgery of the oculomotor muscles].
AB  - The authors evaluated in a retrospective study the results of surgery in 28
      patients with paralysis of the VIth cranial nerve. The standard surgical
      procedure which was selected as primary achieved orhtophoria in 21 patients. In 7
      patients with persisting esotropia and diplopia transposition of the oculomotor
      nerves according to Hummelshein was indicated. After stabilization of the
      postoperative finding in all patients parallel position of the eyes and a
      improved compensatory position of the head was found. Markedly restored motility
      in abduction was observed only in patient. The method of first choice in
      treatment of paralysis of the sixth nerve but also of other oculomotor nerves are
      standard surgical procedures. By retro-position and resection of oculomotor
      muscles usually a satisfactory state in the primary position is achieved.
      Transposition operations are rather useful as supplementary operations in
      previously operated eyes. Indications are persisting diplopia and esotropia.
      Postoperative results as regards the primary position of the eyes are
      satisfactory but usually marked improvement of the motility cannot be foreseen.

PMID- 11338265
TI  - [Mucoceles of paranasal sinuses].
AB  - In a retrospective study authors refer to the treatment results in four patients
      with mucocele of the paranasal sinuses, who were hospitalized during a 30-months
      period at the Department of Otorhinolaryngology of the Charles University
      Hospital, in Prague, Czech Republic. In all patients the frontal sinus was
      involved, in three cases the involvement was unilateral, in one case bilateral.
      In the medical history of all patients, an injury, inflammation, or surgery of
      the paranasal sinus in the past (5-30 years ago) were present. In three patients,
      proptosis of the eye, swollen upper eyelid, and diplopia were discovered firstly
      by ocular examination. All patients underwent external approach surgical
      treatment, in four cases it was the frontoethmoidectomy sec. Jansen-Ritter, in
      one case the osteoplastic frontal craniotomy was performed. The postoperative
      follow-up period is 2-30 months.

PMID- 11338266
TI  - [Importance of correct interpretation of incidental detection of intraocular
      administration of silicone oil on the CT image].
AB  - Liquid silicone is used in ophthalmology as one of the possible substitutes of
      the vitreous body and for internal tamponade of the vitreous space in pars plana
      vitrectomy (PPV). The intraocular presence of silicone causes marked changes of
      the CT image of the bulbus. As the number of patients treated by PPV is steadily
      increasing (this applies in particular to patients with diabetes and AIDS), the
      probability increases that the radiologist will encounter this image. Typical
      changes in the CT image of the bulbus after PPV using a silicone cerclage strip
      with administration of silicone oil (SO) into the vitreous space: 1.
      Disfiguration of the bulbus after application of the cerclage strip, 2. the area
      of the vitreous body is visualized as a hyperdense area with a slit-like
      hypodense space between SO and the bulbar wall. Knowledge of these changes will
      avoid errors in the interpretation of accidentally recorded CT images.

PMID- 11338267
TI  - [Cataract surgery in children].

PMID- 11338268
TI  - [Therapy of age-related macular degeneration].

PMID- 11338269
TI  - [Use of drainage implants in the treatment of glaucoma. II].

PMID- 11338270
TI  - [Cataract surgery in eyes treated with vitrectomy for idiopathic macular holes].
AB  - The authors evaluated the final functional results in 30 eyes where on account of
      nuclear and cortical cataract an intraocular lens was implanted. The operation
      was preceded by pars plana vitrectomy (PPV) with internal gas tamponade on
      account of an idiopathic macular hole (IMD). The cataract the development of
      which was recorded in 57 eyes was the manifestation of a late postoperative
      complication from a total number of 84 phakic eyes (67.9%) which were operated on
      account of IMD between April 1996 and June 1999. After cataract surgery the
      corrected visual acuity improved in 23.3% eyes. The investigation confirmed
      improvement and stabilization of the final corrected visual acuity in 24 eyes
      (80%) and confirmed the importance of these surgical procedures.

PMID- 11338271
TI  - [Long-term monitoring of visual function after anatomically successful surgical
      treatment of idiopathic macular holes].
AB  - PURPOSE: The purpose of the study is to determine the outcomes of long-term
      changes and evolution of visual acuity in patients undergoing anatomically
      successful macular hole surgery. MATERIALS AND METHODS: Into prospective study
      are enrolled 20 eyes (20 patients). All patients were successfully operated for
      idiopathic macular hole between September, 1996 and August, 1998. Time of follow
      up ranged from 20 to 43 months (mean, 29.5). The best corrected visual acuity was
      examined before operation and every 3 months after surgery. 12 eyes were operated
      for complicated cataract. The subgroup of 16 eyes was selected from the group of
      20 eyes. The subgroup consisted of patients, who in the first examination
      observed in Watzke-Allen test the interruption of ray of light and there was a
      central scotoma on the campimetry. These tests were realised before operation and
      in the 3rd, 9th and 15th months after operation. Fisher's test and Student's t
      test were used for statistical analysis. RESULTS: Mean corrected visual acuity
      before operation was 0.21. Best corrected visual acuity was 0.44, reached in the
      12th months. Improvement in +2 or more lines was reached in 55%. In 15th and 18th
      months the mean corrected visual acuity decrease because of the progression of
      nuclear sclerosis. 12 eyes were operated for complicated cataract. The best
      corrected visual acuity before and after surgery of idiopathic macular hole was
      0.18 respectively 0.39 and improvement in +2 or more lines was reached in 6 (50%)
      eyes. After surgery of complicated cataract the mean visual acuity was 0.49.
      Further improvement in +2 or more lines was reached in 2 (16.7%) eyes, together
      in 8 (66,%) eyes. Statistical analysis (Fischer's tests, Student's t test) was
      significant (P < 0.05). In the subgroup of 16 eyes, where were followed changes
      in Watzke-Allen test, the interruption of ray of light was in all 16 (100%)
      patients. In the 3rd month 6 (37.5%) patients observed interruption of ray of
      light and other 10 (62.5%) observed deformation in the central part of ray of
      light. In 9th and 15th months the interruption observed 5 (31.25%) patients.
      Deformation in 9th and 15th months observed 8 (50%) respectively 5 (31.25%)
      patients. Gradual decrease of central scotoma observed in the 3rd, 9th and 15th
      month 10 (62.5%), 13 (81.25%) and 14 (87.5%) patients. During the follow up in 12
      (75%) patients was reached total disappearance of central scotoma. CONCLUSIONS:
      The evolution of visual acuity after anatomically successful surgery of
      idiopathic macular hole is dynamic, long-standing and continual process.
      Improvement of visual acuity can be masked by progression of complicated cataract
      nuclear sclerosis. Further improvement of visual acuity can be observed after of
      the surgery complicated cataract.

PMID- 11338272
TI  - [Results of a prospective clinical study of 150 implanted AcrySof lenses].
AB  - The authors present results of a prospective clinical study with 150 foldable
      acrylic intraocular lenses AcrySof (Alcon Pharmaceuticals, Ltd.). There were 70
      women and 63 men, altogether 133 patients (150 eyes). All lenses were implanted
      in the bag through 3.5 mm corneal self sealing tunnel incision. Best corrected
      visual acuity was 6/9 or better in 119 eyes (79.3%) on the first postoperative
      day and in 128 eyes (85.3%) one year after surgery. Induced astigmatism was up to
      0.5 D in 91 eyes (60.7%) on the first postoperative day and in 125 eyes (83.3%)
      six months after surgery. Posterior capsule fibrosis occurred only in 4 eyes one
      year after surgery and in 2 eyes Nd:YAG kapsulotomy was done. We have not seen
      any serious complications. Assessment of the results with AcrySof implantation
      has shown excellent results, especially very low rate of secondary cataract.

PMID- 11338273
TI  - [Binocular vision after cataract surgery in children--long-term results].
AB  - PURPOSE: To evaluate quality of binocular vision in dependence on type of
      cataract, time of surgery and type of aphakic correction with minimal 5 years
      follow up. METHODS: 127 children divided into 3 groups: Group A--24 children with
      monolateral congenital cataract, Group B--56 children with bilateral congenital
      cataract, Group C--47 children with traumatic cataract. Binocular vision results
      were evaluated 5-10 years after cataract surgery subordinated on the type of
      aphakic correction-PC IOL, contact lenses, spectacles, type of cataract
      (congenital mono or bilateral, traumatic) and time of cataract surgery. RESULTS:
      Group A: Binocular vision in 56% children with cataract surgery in the first 3
      months of age and only 20% of binocular vision in children operated later.
      Binocular vision results in dependence on aphakic correction (46% in contact lens
      subgroup, 44% in PCIOL subgroup without statistically significant differences.
      Group B: Binocular vision in 76% of children operated in the first 3 months of
      age, and 79% of children operated later. Binocular vision in 68% of children in
      spectacle aphakic correction subgroup, 67% of children in contact lenses
      subgroup, and 75% of children in primary or secondary implanted PC IOL subgroup.
      Group C: Binocular vision in 80% of children with contact lenses subgroup, and in
      84% of children with implantation PC IOL. CONCLUSION: Better results of binocular
      vision quality have children with cataract extraction in the first three months
      of age then children operated later in group with monolateral congenital
      cataract. Primary or secondary implantation of PC IOL was find to the better
      aphakic correction for the binocular visual results in the groups with bilateral
      congenital cataract and traumatic cataract than other types of aphakic
      correction. Amblyopia is a major determinate of visual outcome in childhood
      cataract. The timing of surgery--the early cataract removal will continue to be
      more important than the method of aphakic optical correction, especially in the
      case of monolateral congenital cataract.

PMID- 11338274
TI  - [Effect of cataract surgery on contrast sensitivity].
AB  - The authors examined in a group of patients with cataract the visual acuity on
      Snellen's optotypes and contrast sensitivity using Pelli-Robson's test before
      cataract surgery and after cataract extraction and implantation of an intraocular
      lens. A VF-7 questionnaire was used for subjective evaluation of the result of
      surgery. The values of contrast sensitivity of the pseudophakic eyes were
      compared with the contrast sensitivity of eyes of a age-matched control group
      with a natural lens. After cataract surgery and lens implantation highly
      significant improvement of visual acuity of the operated eye was recorded. There
      was also significant improvement of binocular contrast sensitivity in the study
      group. The authors did not detect a significant difference of the contrast
      sensitivity of eyes with a PMMA lens and eyes with a silicone lens. There was no
      significant difference in the contrast sensitivity of pseudophakic eyes and
      phakic eyes of the control group. The CF-7 questionnaire revealed that cataract
      surgery led to significant improvement of the investigated visual activities, as
      apparent from the subjective evaluation by the patients. However, no significant
      correlation was found between objective (contrast sensitivity) and subjective (VF
      7 questionnaire) evaluation of cataract surgery. Only one question in the
      questionnaire correlated significantly with contrast sensitivity. The authors
      found a significant reduction of contrast sensitivity caused by an altered
      transparency of the lens. The decline of contrast sensitivity in eyes with
      cataract and relatively good vision on Snellen's optotypes is the cause of some
      subjective complaints of the patients and may be an important factor in
      indication of cataract surgery of eyes with a relatively good visual acuity.

PMID- 11338275
TI  - Psychological adjustment of siblings to a child with diabetes.
AB  - This article presents results of a study examining the psychological adjustment
      of well child siblings living in the same household as siblings with diabetes. A
      sample of 28 well siblings between the ages of eight and 12 were studied.
      Psychological adjustment was assessed by measuring self-concept, behavioral
      difficulties and competence, anxiety, and depression on standardized tests. A
      semistructured interview reported data gathered on the well siblings' emotional
      feelings and their communication patterns. The well siblings demonstrated
      significant internal psychological stressors and maintained high levels of
      behavioral competence. The internal stressors originated from anxiety and low
      self-concept. Recommendations based on the findings are offered to professionals
      who work with children with diabetes and their families.

PMID- 11338276
TI  - Challenges of type 2 diabetes and role of health care social work: a neglected
      area of practice.
AB  - Across the world, diabetes mellitus is one of the most prevalent and serious
      chronic diseases. In the United States alone, almost 16 million people suffer
      from diabetes, which costs many of them their eyesight, kidney function, lower
      limbs, or life itself, and costs the U.S. health care system billions of dollars.
      Currently, social work involvement with this chronic disease appears limited;
      however, social workers have the potential to make remarkable differences in the
      lives of people coping with diabetes. To facilitate involvement, this article
      outlines the basic aspects of Type 2 diabetes mellitus, its biopsychosocial
      challenges, and the roles health care social workers that may be assumed in
      assisting adult patients and their families.

PMID- 11338277
TI  - America's health at the millennium: imminent risks and long-range goals.

PMID- 11338278
TI  - The need to revise assumptions about the end of life: implications for social
      work practice.
AB  - During the 20th century the experience of dying changed dramatically. At the
      beginning of the 1900s, dying and death were integral parts of the life
      experience of most people at any age. Many deaths occurred at home following a
      short course of illness largely unaffected by the limited medical care available.
      At the beginning of the 21st century, in many cases, the process of dying has
      become invisible. Today, most deaths occur in old age. Social workers have a key
      role as "context interpreters" in helping people at the end of life and their
      families understand the natural course of the illness, the process of dying, and
      the advantages and drawbacks of medical interventions. An expanded role for
      social workers in helping people comprehend the medical and social contexts
      within which they face end-of-life decisions is discussed.

PMID- 11338279
TI  - The crisis of public health: implications for social workers.

PMID- 11338280
TI  - The health care crisis in the United States: a call to action.

PMID- 11338281
TI  - "I'm special, too": promoting sibling adjustment in the neonatal intensive care
      unit.

PMID- 11338282
TI  - Influence of family structure on health among youths with diabetes.
AB  - Type 1 diabetes mellitus is a chronic metabolic disorder and is one of the most
      common chronic diseases in childhood. The study discussed in this article
      examined the extent to which family structure is significantly associated with
      health in youths with Type 1 diabetes. A convenience sample of 155 children with
      diabetes and their mothers completed face-to-face interviews; multiple regression
      analyses were conducted. Findings demonstrated that family structure remains a
      significant predictor of youths' health when statistically controlling for race,
      child's age, family socioeconomic status, and adherence. Social workers in
      outpatient medical settings are in a unique position to develop family-oriented
      strategies targeting this neglected area of primary care.

PMID- 11338283
TI  - The prevalence of atopic disorders in children with chronic otitis media with
      effusion.
AB  - We studied 209 children, referred to a multi-disciplinary 'Glue ear/Allergy'
      clinic at our hospital with a history of chronic or recurrent otitis media with
      effusion (OME), in order to determine the prevalence of atopic disease in this
      population. Referrals were made either from within the hospital by Ear, Nose and
      Throat (ENT) Surgeons and Audiological Physicians (internal), or by General
      Practitioners (external). Assessment of atopic status was based on medical
      history, physical examination, nasal smears and skin-prick testing (SPT) in all
      children; and on blood eosinophil counts and total immunoglobulin E (IgE) levels
      in a randomly selected subset. The main outcome measures were number of children
      with rhinitis, asthma, eczema, positive SPT, raised IgE level (> 100 IU/l), and
      nasal and blood eosinophilia. We found allergic rhinitis in 89%, asthma in 36%,
      and eczema in 24%. SPTs were positive to one or more of eight common inhalant
      aeroallergens in 57% of children. Blood tests in the selected subset revealed
      eosinophilia in 40% and a raised serum IgE in 28%. The worldwide prevalence of
      allergic rhinitis in children has been estimated to be 20%. The 89% prevalence
      found in this study is very high and there are a number of reasons which suggest
      that there may be a causal relationship. Whole-population studies will be
      required to confirm these findings, which could have important therapeutic
      implications for OME.

PMID- 11338284
TI  - A contiguous deletion syndrome of X-linked agammaglobulinemia and sensorineural
      deafness.
AB  - Hearing loss in patients with X-linked agammaglobulinemia is often attributed to
      recurrent infections. However, recent genetic studies suggest a different
      etiology in some patients. We present three unrelated patients, 6, 9, and 14
      years of age, with large deletions of the terminal portion of the Bruton tyrosine
      kinase (Btk) gene extending 4.2-19 kb beyond the 3' end of the gene. The DNA
      immediately downstream of the 3' end of Btk contains the deafness-dystonia
      protein gene (DDP). Mutations in this gene have recently been shown to underlie
      the Mohr-Tranebjaerg syndrome, which is characterized by sensorineural deafness,
      dystonia, and mental deficiency. Besides the immunodeficiency, our patients
      exhibited progressive sensorineural deafness. The clue to an associated hearing
      problem was delayed development of speech in one patient and post-lingual
      deafness noticed between the age of 3-4 years in the other two. These patients
      have not yet exhibited significant associated neurologic deficits.

PMID- 11338285
TI  - Children with food allergy presenting as atopic dermatitis (AD) were compared
      with patients with food allergy and gastrointestinal symptoms.

PMID- 11338286
TI  - Annus horribilis for British medicine.

PMID- 11338287
TI  - Detection of Fel d 1-immunoglobulin G immune complexes in cord blood and sera
      from allergic and non-allergic mothers.
AB  - It is an established fact that T-cell responses of fetal origin to inhalant
      allergens are present in most cord blood samples. These immune responses could be
      explained by trans-placental passage of peptides, either as free antigens or in
      complexes with immunoglobulin G (IgG), providing the fetus with a trigger for
      priming the T-cell system already present in utero. The aim of this study was to
      investigate the presence of the major cat allergen, Fel d 1, in complexes with
      IgG in cord blood and maternal sera. Serum samples from 75 mothers (38 allergic,
      37 non-allergic), and cord blood from their infants, were investigated for the
      presence of Fel d 1-IgG immune complexes (ICs) by using an amplified enzyme
      linked immunosorbent assay (ELISA). Three monoclonal antibodies to Fel d 1 were
      used for coating. The specificity of the method was confirmed by inhibition
      experiments. ICs of Fel d 1-IgG were detected in the sera of 45% allergic and 49%
      non-allergic mothers, and in, respectively, 34% and 41% of their infants.
      Therefore, neither the prevalence nor the level of ICs were affected by maternal
      allergy. Low levels of trans-placentally transferred ICs can provide the fetus
      with a singal for the priming of T-cell responses to inhalant allergens. However,
      this is not necessarily related to allergic disease.

PMID- 11338289
TI  - Bronchoalveolar lavage in asthmatic children: evidence of neutrophil activation
      in mild-to-moderate persistent asthma.
AB  - Little information is available on cell profiles and mediator production in the
      lower airways of children with asthma by comparison with the adult population. To
      study the bronchoalveolar lavage (BAL) cell profiles and production of eosinophil
      cationic protein (ECP) and myeloperoxidase (MPO) in childhood bronchial asthma, a
      retrospective study was performed in 29 children (13 allergic asthmatic children
      and 16 controls). Six of the asthmatics had mild-to-moderate persistent disease
      and seven had intermittent asthma. The BAL cell count and ECP and MPO values of
      asthmatic children were compared with those from 16 controls. The asthmatic
      patients had higher values than controls for the total cell count (p = 0.08), for
      neutrophils (p = 0.02), and for ECP and MPO (p < 0.001). MPO levels (p = 0.04),
      neutrophil count (p = 0.06), and ECP values (p = 0.06) were higher in patients
      with mild-to-moderate persistent asthma than in those with intermittent asthma.
      Our results demonstrate that neutrophil-mediated inflammation is greater in
      patients with more severe asthma.

PMID- 11338288
TI  - Increased eosinophil cationic protein levels in bronchoalveolar lavage from
      wheezy infants.
AB  - Although studies examining the serum suggest a role for eosinophils in wheezing
      episodes in infants and toddlers, the presence of a chronic eosinophilic
      inflammation within their airways remains to be demonstrated. In this study we
      investigated whether eosinophil cationic protein (ECP) levels are increased in
      BAL fluid (BALF) from infants and toddlers with recurrent wheezing episodes,
      during an asymptomatic period. The levels of ECP in BALF were quantitated by
      radioimmunoassay in 61 children (36 with severe recurrent episodes of wheezing
      and 25 who were non-wheezy), aged 6-36 months, in whom flexible bronchoscopy was
      clinically indicated. BALF eosinophil counts were < or = 1% in all patients and
      did not differ in wheezers, compared to non-wheezers. In contrast, ECP levels in
      BALF were > or = 2.2 micrograms/l in 18 of 36 (50%) wheezy infants but in only
      three of 25 (12%) control infants (p < 0.01). Neutrophil counts were
      significantly higher in the wheezer group than in the non-wheezer group (8.1 x
      10(3) cells/ml vs. 3.0 x 10(3) cells/ml). ECP levels in the BALF were not
      correlated with the absolute number of eosinophils (r = 0.03; p = 0.8) but were
      correlated with the absolute number of neutrophils (r = 0.54; p = 0.001). There
      was no association between high ECP levels in BALF and the atopic status of the
      wheezers. In conclusion, ECP levels are increased in BALF from young children
      with recurrent wheezing episodes, even during relatively quiescent periods,
      suggesting a chronic increased cell activation in the lower airways.

PMID- 11338290
TI  - Prospective, controlled, multi-center study on the effect of an amino-acid-based
      formula in infants with cow's milk allergy/intolerance and atopic dermatitis.
AB  - Cow's milk allergy/intolerance is treated by complete avoidance of cow's milk
      proteins. Because cow's milk is an important food for infants, its avoidance may
      lead to an increased risk of growth impairment. Whilst there is evidence for the
      beneficial effects of extensively hydrolyzed cow's milk formulate (eHF) in
      infants with cow's milk allergy/intolerance, little is known about the effects of
      amino-acid-based formulae (AA) in such infants. We therefore performed a
      prospective, controlled, multi-center trial to study the efficacy of AA in
      comparison with eHF, on the growth and clinical symptoms of 73 infants (median
      age 5.7 months) with cow's milk allergy/intolerance and atopic dermatitis. Cow's
      milk allergy/intolerance was proven in all infants by double-blind, placebo
      controlled food-challenge. We observed a significant improvement in the SCORAD
      index in both groups, from a mean of 24.6, at entry, to a mean of 10.7 (p <
      0.0001) after 6 months. In the AA group there was a significant increase in the
      length standard deviation score (p < 0.04), whilst there was no difference in the
      eHF group. The weight-for-length values were stable in both groups. The energy
      intake during the study was similar in both groups. Both an AA and eHF resulted
      in a significant clinical improvement in infants with an early onset of symptoms
      of cow's milk allergy/intolerance. Feeding an AA resulted in improved growth
      compared with feeding eHF, despite similar dietary intakes, and may therefore be
      considered as a beneficial alternative in infants with severe cow's milk allergy
      intolerance.

PMID- 11338291
TI  - Hypoallergenicity of an extensively hydrolyzed whey formula.
AB  - Several different protein hydrolysate-based infant formulas have been promoted as
      hypoallergenic and considered suitable for the dietary management of cow's milk
      allergy (CMA). Accepting that none of the hydrolysate-based products is
      completely safe, the American Academy of Pediatrics (AAP) recommends that these
      formulas should be tested in a double-blind placebo-controlled setting and
      tolerated by at least 90% of children with proven CMA. In principle, this
      recommendation is also endorsed by the European Society of Paediatric
      Gastroenterology and Nutrition (ESPGAN) and the European Society of Paediatric
      Allergy and Clinical Immunology (ESPACI). In this two-center study, 32 children
      with proven CMA were tested with the extensive hydrolysate whey formula Nutrilon
      Pepti, for comparison with Profylac (extensive) and Nan HA (partial) whey
      hydrolysate products. Skin-prick tests (SPTs) were, respectively, positive to the
      three hydrolysate formulas in 19%, 15%, and 32% of children. After oral challenge
      it was concluded that 97% (95% CI: 85-100%) of the children tolerated Nutrilon
      Pepti, 94% (95% CI: 75-100%) tolerated Profylac, and 64% (95% CI: 37-81%)
      tolerated Nan HA. This study demonstrates that the extensive hydrolysates
      Nutrilon Pepti and Profylac are well tolerated in a population of children with
      proven CMA and that both products can be considered safe for their intended use.
      This study confirms that a very small number of children react even to
      extensively hydrolyzed formulas. SPT prior to oral exposure to the hydrolysate
      based formulas can indicate whether a child is at risk of showing reactions to
      the product. Introduction of new products to these children should be carried out
      under a doctor's supervision. However, the majority of the SPT-positive children
      did tolerate the two extensively hydrolyzed whey-based formulas tested.

PMID- 11338292
TI  - Skin-prick test findings in students from moisture- and mould-damaged schools: a
      3-year follow-up study.
AB  - Dampness and moisture problems in a building may cause growth of moulds, leading
      to sensitization and symptoms in the inhabitants. The mechanism by which
      sensitization to moulds takes place has remained obscure; in particular, the role
      of atopy is not clear. In 1996, 622 pupils (7-13 years of age) attending a school
      with a moisture problem (index school; 414 pupils) and a control school (208
      pupils) were screened using a questionnaire. Two-hundred and twelve children had
      doctor-diagnosed asthma, parental-reported wheezing or prolonged cough, and they
      participated in a clinical study, which included skin prick tests (SPT) to 12
      moulds. An identical, follow-up study was performed 3 years later in 1999. In the
      follow-up study, 144 of the original 212 students participated. They were now
      attending four different schools: the index primary school had been renovated and
      the control school remained unchanged, but the two secondary schools had moisture
      and mould problems. The purpose of the study was to evaluate the occurrence of
      mould allergy in children of school age and to compare sensitization to moulds in
      relation to age, exposure, asthma, and atopy. In 1999, SPT responses to moulds
      were demonstrated in 17 (12%) of the 144 children. Six children had SPT reactions
      > or = 3 mm and all but one were older than 14 years. During the 3-year follow-up
      period, mould allergy developed in five children and disappeared in two children.
      Five of the six children with reactions > or = 3 mm to moulds had positive
      responses to other allergens, five had clinical atopy but only two had asthma.
      Likewise, all six children had been exposed to moisture and dampness in the
      school buildings. In conclusion, mould allergy diagnosed by SPTs was rare in
      students. Most reactions to moulds were in students older than 14 years with
      multiple SPT reactions to common allergens, and there was no significant
      association with asthma.

PMID- 11338293
TI  - International Study of Asthma and Allergies in Childhood: validation of the
      rhinitis symptom questionnaire and prevalence of rhinitis in schoolchildren in
      Sao Paulo, Brazil.
AB  - Written questionnaires (WQ) have been widely used in epidemiologic studies. In
      order to yield comparable results, they must be validated after translation to
      another language. The International Study of Asthma and Allergies in Childhood
      (ISAAC) WQ has been previously validated by a comprehensive study, but its
      validation in Brazil has not been performed. Our objectives were to validate the
      rhinitis component of the ISAAC's self-applicable WQ following its translation to
      Portuguese, and to determine the prevalence of rhinitis and related symptoms
      among Brazilian children living in the city of Sao Paulo. A group of 10
      pediatricians and 10 pediatric allergists graded the questions from 0 to 2 and
      established a maximum score for each question. The WQ was answered by parents or
      guardians of children 6-7 years of age with rhinitis (R) (n = 27) and of control
      children of the same age without rhinitis (C) (n = 27). The WQ was also completed
      by adolescents 13-14 years of age with rhinitis (R) (n = 32) and without rhinitis
      (C) (n = 32). Half of these individuals answered the same WQ after 2-4 weeks, to
      ensure reproducibility. Cut-off scores of 4 and 3 were identified for the 6-7-
      and 13-14-year-old groups, respectively, as scores predictive of rhinitis. The
      prevalence of rhinitis was 28.8% in the group of 3005 children 6-7 years of age
      and 31.7% in the group of 3008 children 13-14 years of age, respectively. Using
      the global cut-off score, these prevalences were even higher, in the order of
      34.7% and 40.7%, respectively. In conclusion, the rhinitis component of the ISAAC
      WQ was proven to be reproducible, adequate and able to discriminate children and
      adolescents with and without rhinitis, and revealed that the prevalence of
      rhinitis among Brazilian children living in the city of Sao Paulo was as high as
      the prevalence of rhinitis in other areas of the world.

PMID- 11338294
TI  - Heterogeneity of host immunological risk factors in patients with aggressive
      periodontitis.
AB  - BACKGROUND: The pathogenesis of early-onset periodontitis (EOP) can be explained
      by various host risk factors. Previous studies have focused on a single (among
      many possible) immunological risk factor and the association among the factors
      has not been assessed. We comprehensively investigated the associations among
      multiple host immunological risk factors in EOP patients to further elucidate
      their role in the pathogenesis of EOP. METHODS: Sixty-eight EOP patients (50
      generalized EOP, 18 localized EOP), 51 EOP-suspected patients (S-EOP), 43 adult
      periodontitis (AP) patients, and 36 periodontally healthy subjects (HS)
      participated in this cross-sectional study. We examined peripheral neutrophil
      functions, phenotypic and functional characterization of peripheral lymphocytes
      (lymphocyte subsets, T-cell proliferative activity), cytokine productivity
      (interleukin [IL]-1, IL-2, tumor necrosis factor [TNF]-alpha, interferon [IFN]
      gamma, IL-4 and IL-6), serum immunoglobulin G (IgG) antibody titers against 12
      periodontal bacteria, and HLA class II genotypes. RESULTS: G-EOP, S-EOP, and AP
      patient groups showed significantly lower percentages of pan T cells and CD8
      positive cells (P < 0.02) compared with the HS group. L-EOP patients showed
      depressed IL-4 and TNF-alpha productivity compared with the HS group (P < 0.02).
      The EOP group showed significantly elevated antibody levels against
      Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Treponema
      denticola, and Fusobacterium nucleatum compared with the HS group (P < 0.05). The
      frequency with DQB1*0503 was significantly higher in the EOP patient group than
      the HS group (P = 0.045) due to the higher frequency in L-EOP patients than the
      HS group (P = 0.035). There were wide interindividual variations in each of the
      tests among patient and HS groups; however, EOP patients showed wider
      intradiagnostic group variations in certain host defensive cell functions than
      the other groups. There were some EOP patients who showed extremely low or high
      values in some tests; the EOP patients could be further divided into subgroups
      according to their host defensive and immunological profiles. However, there was
      heterogeneity in some of the other host immunological tests even in the
      subgroups. CONCLUSIONS: The association of host immunological risk factors in EOP
      patients is widely varied and more complex than previously thought. These results
      indicate the difficulty of explaining the pathogenesis of EOP based on a single
      host risk factor and also emphasize the importance of critical assessment of not
      only EOP patient groups, but also individual patients.

PMID- 11338295
TI  - Effect of nicotine on fibroblast beta 1 integrin expression and distribution in
      vitro.
AB  - BACKGROUND: Integrins are a family of transmembrane cell surface glycoproteins,
      and those with the beta 1-subunit function in both cell-to-cell and cell-to
      substrate adhesion. The purpose of this study was to determine nicotine's effect
      on the expression and distribution of the beta 1 integrin subunit on the human
      gingival fibroblast cell surface. METHODS: Pure nicotine was diluted in medium to
      the following concentrations: 0 (control), 0.025, 0.05, 0.1, 0.2, and 0.4 microM.
      Human gingival fibroblasts (HFG) were grown for 24 hours in each concentration
      and fluorescein-labeled with a mouse monoclonal anti-human beta 1 antibody and
      secondarily incubated with a urease-labeled anti-mouse IgG antibody. After a
      final wash, the cells were incubated with urea/bromcresol blue substrate for 15
      minutes at 37 degrees C and measured in a microplate reader at 570 nm. RESULTS:
      The integrin beta 1-subunit was detected on the HGF surface membrane by
      fluorescence labeling, and cell-enzyme-linked immunosorbent assay testing
      demonstrated its decreased expression with increasing nicotine concentrations
      that were statistically different at the concentrations of 0.2 and 0.4 microM
      versus controls (P < 0.05). CONCLUSIONS: Nicotine concentrations of 0.2 and 0.4
      microM significantly decrease beta 1 integrin expression in human gingival
      fibroblasts that may affect cell-cell and cell-substratum adhesion during wound
      healing.

PMID- 11338296
TI  - Keratinocyte growth factor expression in human gingival fibroblasts and
      stimulation of in vitro gene expression by retinoic acid.
AB  - BACKGROUND: Keratinocyte growth factor (KGF) is a stromally derived growth factor
      of the fibroblast growth factor (FGF) family with paracrine effects targeted to
      influence the growth and differentiation of epithelia. Regional and temporal
      changes in KGF expression play important roles in the development and maintenance
      of epithelial structures and in epithelial wound healing. Differing patterns of
      expression of KGF by fibroblasts in the gingival region could therefore be
      related to the observed regional variation in the differentiation and behavior of
      gingival epithelia. METHODS: The in vitro and in vivo patterns of expression of
      KGF mRNA in human gingival and periodontal fibroblasts were examined using
      reverse transcription polymerase chain reactions (RT-PCR) and in situ
      hybridization with digoxigenin-labeled riboprobes. The patterns observed for
      human gingiva were compared with those for human skin and for murine tissues.
      RESULTS: Gingival and periodontal fibroblasts showed expression of KGF
      transcripts in vitro, and the degree of expression was markedly influenced by the
      presence of retinoic acid, an agent known to influence patterns of epithelial
      differentiation. Sections of human and murine gingiva and skin showed regionally
      variable expression of transcripts with the cells expressing KGF in the
      subepithelial, rather than the deeper, connective tissues and periodontium.
      CONCLUSIONS: The results point to a role of KGF in the maintenance of normal
      growth and differentiation of gingival epithelia. A lack of KGF expression by
      periodontal fibroblasts in vivo is expected to hinder apical epithelial migration
      and thus stabilize the epithelial attachment. The effects of retinoic acid (RA)
      on KGF expression in vitro provide an indirect mechanism by which RA may regulate
      the growth and differentiation of gingival epithelia.

PMID- 11338297
TI  - The characteristic cellular organization and CEACAM1 expression in the junctional
      epithelium of rats and mice are genetically programmed and not influenced by the
      bacterial microflora.
AB  - BACKGROUND: The epithelial cell adhesion molecule CEACAM1 exhibits an interesting
      dynamic expression during tooth development. It is first expressed in the reduced
      enamel epithelium, its expression then increases in the orally faced reduced
      epithelium and the overlying oral epithelium that then fuse to give rise to the
      junctional epithelium. The expression of CEACAM1 remains at high levels in the
      junctional epithelium, in contrast to the surrounding oral sulcular epithelium
      which shows much lower expression levels. We investigated if the high expression
      levels of CEACAM1 and the loosely organized cells characteristic of the
      junctional epithelium are genetically programmed or result from bacterial
      infiltration. METHODS: Oral tissues from germ-free rats and mice and animals with
      conventional bacterial flora were analyzed by transmission electron microscopy
      and immunohistochemical staining for CEACAM1. RESULTS: The junctional epithelium
      of both germ-free and conventional animals was identical with respect to both
      CEACAM1 expression and morphology. Also the presence of leukocytes was the same
      in both types of animals. CONCLUSIONS: The results indicate that the
      characteristic morphology and the high expression levels of CEACAM1 in the
      junctional epithelium are genetically programmed and not a result of bacterial
      infiltration. This suggests that CEACAM1 has an important role for the structural
      integrity of the junctional epithelium. This conclusion was supported by the
      observation that the junctional epithelium does not express any E-cadherin, which
      is another abundant epithelial cell adhesion molecule.

PMID- 11338298
TI  - Cyclooxygenase-2 is upregulated in inflamed gingival tissues.
AB  - BACKGROUND: Increased release of prostaglandins (PG) within periodontal tissues
      is considered to play a pathogenetic role during periodontal disease progression.
      The rate-limiting step in the formation of PG from arachidonic acid is catalyzed
      by cyclooxygenase (COX). Currently there are 2 known isoforms of the enzyme. COX
      1 is constitutively expressed in various tissues whereas COX-2 is an inducible
      enzyme believed to be responsible for PG synthesis at sites of inflammation. The
      purpose of this study was to compare COX-2 expression in inflamed and healthy
      human gingiva and further explore some of the pathogenetic mechanisms which may
      lead to elevated COX-2 expression in vivo. METHODS: Thirty-two gingival biopsies
      were obtained during routine oral surgical procedures and were processed
      histologically using hematoxylin and eosin to determine the degree of
      inflammation. Of these biopsies, 7 with low and 7 with high histological levels
      of inflammation were further processed immunohistochemically in order to assess
      the levels of COX-2 expression in situ. To explore some potential mechanisms of
      COX-2 upregulation, gingival connective tissue primary cell cultures were
      established and challenged with periodontal bacteria or proinflammatory cytokines
      in vitro. The levels of COX-2 expression were analyzed by Western blot of cell
      lysates. COX-2 activity was assessed by quantifying prostaglandin E2 (PGE2)
      levels in culture supernatants by competitive EIA. RESULTS: We have shown by
      immunohistochemistry that COX-2 expression was significantly higher (P < 0.01) in
      tissues with higher levels of inflammatory infiltrates. Expression of COX-2 was
      detected in gingival epithelium, endothelial cells as well as cells with
      fibroblast morphology. In vitro studies indicated that gingival fibroblasts (GF)
      did not express COX-2 constitutively. However, when these cells were challenged
      with interleukin (IL)-1 beta or bacterial cells (A. actinomycetemcomitans JP2 or
      B. forsythus ATCC 43037), COX-2 expression as well as COX-2 activity were
      upregulated. COX-2 expression was upregulated as early as 2 hours post IL-1 beta
      challenge and was accompanied by a sustained PGE2 release in the culture
      supernatants. Cyclosporin A (CsA) did not inhibit COX-2 expression induced by
      bacterial challenge. In contrast, NS-398, a selective inhibitor of COX-2
      activity, almost completely abolished PGE2 synthesis by these cells in response
      to bacterial or cytokine challenge. CONCLUSIONS: We conclude that COX-2
      expression is significantly upregulated in inflamed periodontal tissues. Both
      inflammatory cytokines such as IL-1 beta and bacterial constituents may be
      responsible for the enhanced COX-2 expression and PGE2 synthesis in vivo.

PMID- 11338299
TI  - Histological evaluation of healing and revascularization of the subepithelial
      connective tissue graft.
AB  - BACKGROUND: The goal of this investigation was to histologically evaluate the
      healing and revascularization of the subepithelial connective tissue graft in
      dogs. METHODS: Six beagle dogs were used in this study. Recession defects were
      surgically created on maxillary left P2 and right P2, and maxillary and
      mandibular left central and lateral incisors. The defects were left untreated for
      35 days. After elevating a split thickness flap, the graft was harvested from the
      palate and placed over the denuded root surfaces. The flap was then coronally
      repositioned and sutured. Three dogs provided the specimens for 7- and 14-day
      time points and 3 dogs for 28- and 60-day time points. The animals were
      sacrificed and the blocks obtained were divided in half. One half was processed
      following the Spalteholtz method and the other was processed for routine
      histologic examination. RESULTS: At 7 days, a clot was present at the demarcation
      zones and it was more organized at 14 days. At 28 days, the junctional epithelium
      was formed and the demarcation zones could not be delineated. At 60 days, the
      oral epithelium had regained its normal appearance. The attachment of the graft
      to the root surface was mediated by a combination of epithelial downgrowth and
      connective tissue attachment. Minimal new bone and cementum formation was
      observed. The vascularization of the graft at 7 days originated from the
      periodontal plexus and the overlying flap. At 14 days, the graft was completely
      vascularized. At 28 and 60 days, normal vascularization was present. CONCLUSIONS:
      The vascularization of the connective tissue graft originates from the
      periodontal plexus, the supraperiosteal plexus, and the overlying flap. The
      attachment of the graft to the root surface appears to be mediated by a
      combination of epithelial downgrowth and connective tissue attachment. There is
      little potential for new cementum and new bone formation.

PMID- 11338300
TI  - Clinical evaluation and comparison of 2 topical anesthetics for pain caused by
      needle sticks and scaling and root planing.
AB  - BACKGROUND: Pain generated by needle sticks (Ns) for the delivery of local
      anesthetic and/or scaling and root planing (SRP) instrumentation is commonly
      addressed by the use of topical anesthetics, such as a benzocaine-gel preparation
      (BGP). Pain suppression following such use has been highly variable. Development
      of medicine-containing patches and adhesives for intraoral use have led to a new
      approach for topical anesthesia in the form of a transoral lidocaine delivery
      system (LDS). The purpose of this double-blind study was to evaluate the efficacy
      of the LDS and also to compare LDS with BGP for pain suppression to Ns and SRP.
      METHODS: One group of 20 subjects randomly received in both maxillary and
      mandibular molar-bicuspid areas LDS or BGP on one side and non-anesthetic control
      on the other side. A second group of 20 subjects compared the effectiveness of
      LDS directly with BGP in molar-bicuspid areas of both arches. Random order
      determined the selection for each anesthetic tested between the arches and
      bilateral. Pain perception was separately scored to a pain-inducing Ns simulation
      without anesthetic injection at each area and subsequently also to SRP using both
      a verbal pain scale (VPS) and a visual analog scale (VAS). RESULTS: VPS and VAS
      results analyzed by Bonferroni-adjusted Wilcoxon matched-pairs signed-rank tests
      found pain suppression scores significantly (P < 0.005) reduced for Ns by LDS to
      controls and to BGP. Comparing LDS directly with BGP, LDS was significantly (P <
      0.05) more effective in reducing pain to Ns in both arches, to SRP in the
      maxillary arch, and equally effective as BGP in the mandibular arch. CONCLUSIONS:
      LDS is more effective than BGP for topical pain suppression to Ns and SRP in both
      arches.

PMID- 11338301
TI  - The effect of occlusal discrepancies on periodontitis. I. Relationship of initial
      occlusal discrepancies to initial clinical parameters.
AB  - BACKGROUND: A causal relationship between occlusal discrepancies and periodontal
      disease has been postulated in the past. However, animal studies and clinical
      studies have not been able to clearly demonstrate or rule out this potential
      relationship. METHODS: The records from a private practice limited to
      periodontics were reviewed to find patients who had complete periodontal
      examination records, including occlusal analysis, that were recorded at least 1
      year apart. Patients who fit these criteria were divided into a group who had
      none of the recommended treatment (untreated n = 30), those that had only
      nonsurgical treatment (partially treated n = 18), and a control group that had
      complete all recommended treatment (surgically treated n = 41). The data for each
      tooth of each patient, including occlusal status, were placed in a database and
      analyzed using the generalized estimating equations (GEE) method to test for
      associations between initial occlusal discrepancies and various initial clinical
      parameters while adjusting for significant confounders. RESULTS: Teeth with
      initial occlusal discrepancies were found to have significantly deeper initial
      probing depths (P < 0.0001), significantly worse prognoses (P < 0.0001), and
      significantly worse mobility than teeth without initial occlusal discrepancies.
      In addition, this association between initial occlusal discrepancies and initial
      periodontal condition was found to hold for various subsets considered as well,
      including posterior teeth only and when only patients with good oral hygiene were
      considered. CONCLUSIONS: This study indicates that there is a strong association
      between initial occlusal discrepancies and various clinical parameters indicative
      of periodontal disease. Based on adjustments made for other known risk factors
      for periodontal disease, such as smoking, poor oral hygiene, etc., this study
      provides some evidence that occlusal discrepancy is an independent risk factor
      contributing to periodontal disease.

PMID- 11338302
TI  - The effect of occlusal discrepancies on periodontitis. II. Relationship of
      occlusal treatment to the progression of periodontal disease.
AB  - BACKGROUND: A causal relationship between occlusal discrepancies and periodontal
      disease has been postulated in the past. However, minimal data are available
      concerning the effect of treatment of occlusal discrepancies on periodontitis.
      METHODS: The records from a private practice limited to periodontics were
      reviewed to find patients who had complete periodontal examination records,
      including occlusal analysis, that were recorded at least 1 year apart. Patients
      who fit these criteria were divided into a group that had none of the recommended
      treatment (untreated n = 30), those who had only non-surgical treatment
      (partially treated n = 18), and a control group that had completed all
      recommended treatment (surgically treated n = 41). The data for each tooth of
      each patient, including occlusal status, were placed in a database and analyzed
      using the generalized estimating equations method. RESULTS: Worsening in overall
      clinical condition, as measured by worsening in prognosis, indicated that teeth
      with no initial occlusal discrepancies and teeth with treated initial occlusal
      discrepancies were only about 60% as likely to worsen in overall clinical
      condition over time compared to teeth with untreated occlusal discrepancies.
      Teeth with untreated occlusal discrepancies were also shown to have a
      significantly greater increase in probing depth per year than either teeth
      without initial occlusal discrepancies or teeth with treated initial occlusal
      discrepancies (P < 0.001). In addition, teeth with untreated occlusal
      discrepancies had a significant increase in probing depth per year (P < 0.001),
      whereas teeth without initial occlusal discrepancies and teeth with treated
      initial occlusal discrepancies had no significant increase in probing depth per
      year (P > 0.05). CONCLUSIONS: This study provides strong evidence of an
      association between untreated occlusal discrepancies and the progression of
      periodontal disease. In addition, this study shows that occlusal treatment
      significantly reduces the progression of periodontal disease over time and can be
      an important adjunct therapy in the comprehensive treatment of periodontal
      disease.

PMID- 11338304
TI  - The effect of membrane exposure on the outcome of regenerative procedures in
      humans: a meta-analysis.
AB  - BACKGROUND: The significance of early membrane exposure on the regenerative
      outcome in guided tissue regeneration (GTR) and guided bone regeneration (GBR)
      procedures is somewhat controversial. Several clinical trials have shown better
      response when the membranes remained submerged (S) compared to those that have
      become exposed (E) during healing. Other studies have failed to show any such
      difference. Small sample size and/or large standard deviation of the changes
      might account for these discrepancies. The purpose of this meta-analysis is to
      critically combine the existing data in order to provide meaningful information
      based on a large database. METHODS: Studies of GTR in Class II furcation and
      intrabony defects (IBD), together with GBR around dental implants, where the
      membrane became exposed during the postoperative period, were combined to form 3
      separate databases. A meta-analysis was employed to compare the 2 subgroups (E
      versus S) in each of the databases. First, weighted mean changes and weighted
      standard errors were calculated for each subgroup. Next, an individual study P
      value was calculated (1-tailed Student t test); finally, a combined Fisher's P
      statistic (with 5% significance level) was calculated from the individual P
      values. RESULTS: Five studies with a total of 101 sites were included in the
      furcation database; 43 of these sites became exposed. Mean horizontal attachment
      level (AL) gain for the S sites (3.72 +/- 0.15 mm) was slightly greater than that
      of the E sites (3.06 +/- 0.15 mm; P = 0.030257). For the intrabony group, there
      were 309 sites in 5 studies: of these, 142 sites became exposed. Mean gain in
      vertical AL was 4.22 +/- 0.15 mm and 4.69 +/- 0.13 mm for the E and S group,
      respectively (P = 0.011415). The GBR group included 60 sites in 2 studies: new
      bone formation in the 24 S sites (3.01 +/- 0.38 mm) was 6-fold greater compared
      with the 36 E sites (0.56 +/- 0.45 mm). These differences were also statistically
      significant (P = 0.001875). CONCLUSIONS: Membrane exposure during healing had a
      major negative effect on GBR around dental implants but only a minimal effect on
      GTR around natural teeth.

PMID- 11338303
TI  - Peri-implant bone reactions to immediately loaded implants. An experimental study
      in monkeys.
AB  - BACKGROUND: There are reports which demonstrate that immediately loaded splinted
      implants can be osseointegrated when they are placed in the anterior part of the
      lower jaw. The concept of immediate loading has not been well investigated in the
      posterior mandible. The aim of this study was to evaluate the bone reactions
      around immediately loaded implants placed in the posterior region of the lower
      jaw in the monkey model. METHODS: Six adult Macaca fascicularis monkeys were used
      in this study. A total of 36 implants were placed after extraction of the second
      premolars, first and second molars, and complete healing of the sockets. Three
      control (C) group implants were placed in one quadrant of the lower jaw of each
      monkey. After a delay of 3 months to allow osseointegration to take place, the
      implants were loaded for 1 month using temporary resin bridges and later for 2
      months using metal splinted crowns. In the contralateral region of the lower jaw,
      3 test (T) group implants were placed and loaded immediately with the same
      sequence as carried out for the C implants. Specimens were examined and evaluated
      histologically after sacrifice. RESULTS: All of the implants were
      osseointegrated. Compact, cortical bone in contact with the implant surface
      without any gaps or connective tissue formation was observed. CONCLUSIONS: It was
      concluded that immediately loaded, splinted implants can be osseointegrated with
      a similar hard and soft tissue peri-implant response as delayed-loaded implants
      in the posterior mandible.

PMID- 11338305
TI  - Apoptosis in chronic adult periodontitis analyzed by in situ DNA breaks, electron
      microscopy, and immunohistochemistry.
AB  - BACKGROUND: Apoptosis is an evolutionary form of physiological cell death.
      Previous studies suggest that apoptosis is involved in the pathogenesis of
      periodontal diseases. Therefore, we studied the apoptotic events in the gingival
      tissue of chronic adult periodontitis patients. METHODS: Gingival tissue biopsies
      from 22 patients with chronic adult periodontitis and from 11 healthy controls
      were obtained. Criteria for patient inclusion in the periodontitis group were a
      minimum of 14 natural teeth, excluding third molars, with at least 10 posterior
      teeth; 5 to 6 sites with probing depth > or = 5 mm; attachment loss > or = 3 mm;
      and extensive radiographic bone loss. The control group included healthy subjects
      with no prior history of periodontal disease. Apoptosis was determined using the
      terminal TdT-mediated dUTP-biotin nick end labeling (TUNEL) technique; electron
      microscopic analysis; and expression of Caspase-3, Fas, FasL, Bcl-2, and p53 by
      immunohistochemistry. RESULTS: TUNEL-positive cells and cells exhibiting
      chromatin condensation by electron microscopy were observed in the inflammatory
      infiltrate of biopsies obtained from periodontitis patients. Most of the TUNEL
      positive cells belonged to neutrophil cell populations as they were stained with
      anti-myeloperoxidase. Positive staining for active-caspase 3, Fas, FasL, and p53
      was only observed in the inflammatory infiltrate from periodontitis biopsies,
      whereas Bcl-2 cells were present in both periodontitis patients and healthy
      controls. CONCLUSIONS: Our findings establish that apoptosis is induced in the
      periodontal tissue by host and microbial factors and support the hypothesis that
      apoptotic mechanisms could be implicated in the inflammatory process associated
      with gingival tissue destruction observed in adult periodontitis patients.

PMID- 11338306
TI  - Evaluation of transforming growth factor-beta 1 level in crevicular fluid of
      cyclosporin A-treated patients.
AB  - BACKGROUND: The aim of the present study was to investigate the level of
      transforming growth factor-beta 1 (TGF-beta 1) in gingival crevicular fluid (GCF)
      samples of cyclosporin A (CsA)-treated patients and to compare the results with
      control groups. METHODS: Fourteen renal transplant patients exhibiting severe CsA
      induced gingival overgrowth, 10 patients with chronic gingivitis, and 10 subjects
      with clinically healthy periodontium were included in the study. In CsA-treated
      patients, GCF samples were harvested from sites exhibiting gingival overgrowth
      (CsA GO+) and sites not exhibiting gingival overgrowth (CsA GO-). The TGF-beta 1
      levels in a total of 96 GCF samples from the 34 participants were analyzed by
      enzyme-linked immunosorbent assay. The results were expressed in terms of total
      amount (pg/2 sites) and concentration (ng/ml). RESULTS: TGF-beta 1 total amounts
      in CsA GO+ and CsA GO- sites were similar and significantly higher than that of
      healthy sites (P < 0.02 and P < 0.01, respectively). The total amount of TGF-beta
      1 was also higher in gingivitis sites compared to the healthy sites, but the
      difference was not statistically significant (P > 0.05). CsA GO+ and CsA GO-
      sites exhibited higher total amount and concentration of TGF-beta 1 than that of
      gingivitis sites, but the differences were insignificant (P > 0.05). CONCLUSIONS:
      The results of the present study support the theory that CsA increases the
      synthesis of TGF-beta 1 in GCF. However, since the difference between CsA GO+ and
      CsA GO- sites was not statistically significant, it seems unlikely that GCF TGF
      beta 1 level is the sole factor responsible for the CsA-induced gingival
      overgrowth. Complex interactions between various mediators of inflammation and
      tissue modeling are possibly involved in the pathogenic mechanisms of this side
      effect.

PMID- 11338307
TI  - Does nifedipine aggravate cyclosporin--induced gingival overgrowth? An experiment
      in rats.
AB  - BACKGROUND: Nifedipine (NIF) may aggravate cyclosporin A (CsA)-induced gingival
      overgrowth because the potentiated gingival overgrowth has been observed in the
      patients treated with CsA and NIF. The purpose of this study was to evaluate
      whether NIF could aggravate the CsA-induced gingival overgrowth in a rat model.
      METHODS: Ninety male Sprague-Dawley rats were divided into 6 groups: the first
      group received 8 mg/kg of CsA daily by gastric feeding for 6 weeks; the second
      and third groups received NIF daily at a dosage of 10 or 50 mg/kg; the fourth and
      fifth groups received CsA (8 mg/kg) and NIF (10 or 50 mg/kg); and the sixth group
      received solvents as a negative control. Gingival dimensions (including bucco
      lingual depth, mesio-distal width, and vertical height) were assessed bi-weekly
      from impressed stone models of the mandibular incisal region. At the end of the
      experiment, the animals were sacrificed. Following histopathological procedures,
      serial horizontal sections were obtained at the base of the central incisal
      papilla. Two tissue levels were selected for histometric analysis. Level 1 was
      defined as the point where the lingual gingiva embraced the bucco-lingual
      midpoint of the roots and the level 2 as the point where the lingual gingiva at
      the enamel-dentinal junction approximated the bucco-proximal angle of the roots.
      The bucco-lingual depth and the mesio-distal width of the papilla were recorded
      on 5 consecutive sections at the 2 levels, respectively. RESULTS: At the 6-week
      observations, the gingival dimensions (including the depth, width, and height)
      significantly increased after CsA therapy and the increasing treatment duration;
      however, only the mesio-distal width increased after NIF therapy. For NIF therapy
      alone, a positive linear relation was noted by increased NIF treatment dosages in
      all gingival dimensions at week 6. But, this relationship was not found in the
      combined therapies. By histometry, tissue dimensions increased following single
      drug therapy, either CsA or NIF, at both levels. In animals with the combined
      therapies, the tissue dimensions decreased if the animals received 10 mg NIF,
      while they rebounded to control levels with the 50 mg dosage. A dose-dependent
      positive pattern by NIF was noted in tissue dimensions, but the pattern did not
      occur in animals that received combined therapy. CONCLUSIONS: The gingival
      dimensions increased after CsA or NIF therapy, although they were more prevalent
      with CsA. But the augmenting pattern in gingival morphology observed with CsA
      therapy decreased when the animals received additional NIF. Therefore, we
      question whether NIF is a critical factor in aggravating the CsA-induced gingival
      overgrowth.

PMID- 11338308
TI  - Treatment of a human transosseous mandibular defect by guided bone regeneration.
AB  - The treatment of through-and-through human periapical lesions by barrier membrane
      techniques has not been reported in the periodontal literature. However,
      periodontists frequently perform this treatment. The authors present a case that
      demonstrates radiopacity after regeneration surgery of a human periapical
      transosseous mandibular defect, suggesting local bone regeneration. The surgical
      technique performed in this case was based on the principles of guided bone
      regeneration using a demineralized freeze-dried bone membrane (DFDBM). The bone
      membrane acted as an efficient barrier that excluded the nonosteogenic tissue.
      Radiographic findings demonstrated bone fill after 8 months.

PMID- 11338309
TI  - Combined mechanical and antibiotic periodontal therapy in a case of Papillon
      Lefevre syndrome.
AB  - BACKGROUND: Papillon Lefevre syndrome (PLS) is a rare entity and, as such, it is
      almost impossible to evaluate an effective therapy in a randomized controlled
      study. The amount of success reported after therapy for prepubertal periodontitis
      (PP) in PLS is highly variable from case to case. The goal of this case report is
      to evaluate the effects of a combined mechanical and antibiotic periodontal
      therapy regimen in the management of PLS. METHODS: A male patient was diagnosed
      as suffering from PP associated with PLS at the age of 7 years. He showed
      hyperkeratosis of the palms and soles, as well as advanced periodontal disease
      already affecting permanent teeth with maximal probing depth and vertical
      attachment loss of 12 mm and 11 mm, respectively. Subgingival debridement was
      performed with simultaneous administration of oral 250 mg amoxicillin 3 times
      daily and 250 mg metronidazole twice daily for one week. Clinical parameters were
      assessed and subgingival plaque was collected from all teeth prior to therapy and
      7 and 26 months after treatment. Selective cultures for A. actinomycetemcomitans
      were incubated for each individual tooth and DNA probe analysis was performed for
      various periodontal pathogens. RESULTS: Prior to combined mechanical and
      antibiotic treatment, all teeth but one harbored Actinobacillus
      actinomycetemcomitans subgingivally. However, at 7 and 26 months after therapy A.
      actinomycetemcomitans could be detected neither by culture nor by DNA probes.
      Clinical parameters improved markedly and teeth erupting after therapy did not
      exhibit attachment loss of more than 1.5 mm during the observation period.
      CONCLUSIONS: Eradication (suppression beneath detection levels) of A.
      actinomycetemcomitans seems to play a significant role in the successful
      treatment of localized prepubertal periodontitis in PLS.

PMID- 11338310
TI  - Epidermolysis bullosa acquisita: clinical manifestations, microscopic findings,
      and surgical periodontal therapy. A case report.
AB  - BACKGROUND: Epidermolysis bullosa acquisita (EBA) is an uncommon, acquired,
      chronic subepidermal bullous disease. This report describes a case of EBA with
      gingival involvement. A 43-year-old woman with EBA was referred to our clinic for
      periodontal therapy because of gingival tenderness and bleeding. She has been on
      cyclosporin A therapy for the last 2 years. METHODS: Clinical findings were
      analyzed. Anterior gingivectomy operations were performed in 2 stages. The
      samples obtained during the surgery were examined using histopathologic,
      immunohistologic, and electronmicroscopic methods. Long-term effects of the
      surgical periodontal treatment on gingiva were evaluated both clinically and
      microscopically. RESULTS: The dentition displayed minimal enamel hypoplasia.
      Decayed, missing, and filled surfaces score was found to be elevated. Periodontal
      examination showed generalized diffuse gingival inflammation and gingival
      enlargement localized mainly to the anterior region. Nikolsky's sign was
      positive. However, wound healing was uneventful after the operations. Microscopic
      findings were similar to those obtained from the skin. Twenty-one months after
      the operations, Nikolsky's sign was negative and no remarkable gingival
      inflammation was noted. Microscopic examination revealed that the blisters were
      fewer in number and smaller in size. CONCLUSIONS: These results indicate that
      gingival tissues may also be involved in EBA. Uneventful wound healing after
      periodontal surgery in this case suggests that periodontal surgery can be
      performed in patients with EBA. Moreover, both our clinical and histopathologic
      findings imply that gingivectomy proves useful in maintaining gingival integrity
      in these patients. Our data may also suggest that the patients with EBA are
      highly likely to develop dental caries.

PMID- 11338311
TI  - Microsurgical approach to periodontal regeneration. Initial evaluation in a case
      cohort.
AB  - BACKGROUND: Improvements in flap design and soft tissue manipulation are
      considered key elements in improving the outcomes of regenerative periodontal
      surgery. Improved visual acuity and better soft tissue handling resulting from
      the application of a microsurgical approach hold great promise to further improve
      predictability of periodontal regeneration. The aim of this study was to
      preliminarily evaluate the outcomes of a microsurgical approach in the
      regenerative therapy of deep intrabony defects. METHODS: This patient cohort
      study involved 26 patients with one deep interdental intrabony defect each. They
      were treated with periodontal regeneration using guided tissue regeneration
      membranes. Defects were accessed with previously described papilla preservation
      flaps performed with the aid of an operating microscope and microsurgical
      instruments. A stringent plaque control regimen was enforced in all the patients
      during the 1-year observation period. Outcomes included evaluation of the
      complete primary closure of the interdental space (closure), gains in clinical
      attachment (CAL), and reductions in probing depths (PD). RESULTS: Closure was
      achieved in all treated defects and was maintained in 92.3% of cases for the
      entire healing period. Associated gains in CAL were 5.4 +/- 1.2 mm on average,
      corresponding to a CAL gain of 82.8 +/- 14.7% of the initial intrabony component
      of the defect. Average PD reduction was 5.8 +/- 1.4 mm and was associated with
      minimal increase in gingival recession (0.4 +/- 0.7 mm). CONCLUSIONS: The use a
      microsurgical approach was associated with very high ability to obtain and
      maintain primary closure of the interdental tissues over the barrier membranes.
      The procedure resulted in clinically important amounts of CAL gains and minimal
      recessions.

PMID- 11338312
TI  - Data, design, and background knowledge in etiologic inference.
AB  - I use two examples to demonstrate that an appropriate etiologic analysis of an
      epidemiologic study depends as much on study design and background subject-matter
      knowledge as on the data. The demonstration is facilitated by the use of causal
      graphs.

PMID- 11338313
TI  - Municipal drinking water nitrate level and cancer risk in older women: the Iowa
      Women's Health Study.
AB  - Nitrate contamination of drinking water may increase cancer risk, because nitrate
      is endogenously reduced to nitrite and subsequent nitrosation reactions give rise
      to N-nitroso compounds; these compounds are highly carcinogenic and can act
      systemically. We analyzed cancer incidence in a cohort of 21,977 Iowa women who
      were 55-69 years of age at baseline in 1986 and had used the same water supply
      more than 10 years (87% > 20 years); 16,541 of these women were on a municipal
      supply, and the remainder used a private well. We assessed nitrate exposure from
      1955 through 1988 using public databases for municipal water supplies in Iowa
      (quartile cutpoints: 0.36, 1.01, and 2.46 mg per liter nitrate-nitrogen). As no
      individual water consumption data were available, we assigned each woman an
      average level of exposure calculated on a community basis; no nitrate data were
      available for women using private wells. Cancer incidence (N = 3,150 cases) from
      1986 through 1998 was determined by linkage to the Iowa Cancer Registry. For all
      cancers, there was no association with increasing nitrate in drinking water, nor
      were there clear and consistent associations for non-Hodgkin lymphoma; leukemia;
      melanoma; or cancers of the colon, breast, lung, pancreas, or kidney. There were
      positive associations for bladder cancer [relative risks (RRs) across nitrate
      quartiles = 1, 1.69, 1.10, and 2.83] and ovarian cancer (RR = 1, 1.52, 1.81, and
      1.84), and inverse associations for uterine cancer (RR = 1, 0.86, 0.86, and 0.55)
      and rectal cancer (RR = 1, 0.72, 0.95, and 0.47) after adjustment for a variety
      of cancer risk/protective factors, agents that affect nitrosation (smoking,
      vitamin C, and vitamin E intake), dietary nitrate, and water source. Similar
      results were obtained when analyses were restricted to nitrate level in drinking
      water from 1955 through 1964. The positive association for bladder cancer is
      consistent with some previous data; the associations for ovarian, uterine, and
      rectal cancer were unexpected.

PMID- 11338314
TI  - Is drug treatment of hypertension in clinical practice as effective as in
      randomized controlled trials with regard to the reduction of the incidence of
      stroke?
AB  - The results from several nonexperimental studies suggest that drug treatment of
      hypertension in daily clinical practice may not be as effective as in randomized
      controlled trials. These nonexperimental studies had limitations with regard to
      the selection of an appropriate control group. The objective of our study was to
      assess the effect of drug treatment of hypertension under circumstances of
      everyday medical practice on the incidence of stroke by using a prognostically
      comparable untreated reference group. Within two prospective, population-based
      cohort studies among 45,000 men and women 20 years of age and older in the
      Netherlands, we selected a cohort of 2,301 hypertensive subjects who either
      received drug treatment for hypertension (N = 1,318) or were untreated for
      hypertension but were determined to be "candidates" for drug treatment on the
      basis of their level of blood pressure and the presence of other cardiovascular
      risk factors (N = 983). Follow-up averaged 4.6 years and was complete for 91% of
      the hypertensives. Compared with untreated hypertensive subjects who were
      "candidates" for drug treatment, subjects who received drug treatment for
      hypertension had, after adjustment for potential confounders, a 39% [95%
      confidence interval (CI) = 3-61%] reduced risk of stroke. About 46 (95% CI = 29
      599) hypertensive patients need to be treated with antihypertensive drugs for 5
      years to prevent one stroke in the general Dutch population. When a
      prognostically comparable reference group is used, the drug treatment of
      hypertension under circumstances of everyday medical practice appears to be
      effective in the reduction of the incidence of stroke. The relative risk
      reduction that we found was similar to those found in randomized controlled
      trials.

PMID- 11338315
TI  - A cohort study of stress and the common cold.
AB  - The common cold is one of the major causes of work absenteeism. Former studies,
      based on artificial inoculation of rhinovirus, implicated psychological stress in
      the occurrence of this syndrome, either by increasing susceptibility to the virus
      or by causing the subject to overrate the perception of the symptoms.
      Nevertheless, few studies on the effect of stress on the naturally acquired
      common cold have been conducted. We carried out a 1-year prospective cohort study
      among the faculty and staff of a Spanish university (N = 1,149). By means of
      standardized questionnaires, validated in a random sample of the population, we
      assessed the relation between the occurrence of common cold episodes and exposure
      to four dimensions of stress: stressful life events, negative affect, positive
      affect, and perceived stress. All four aspects of stress were related to the
      occurrence of the common cold. Subjects with a high (fourth quartile) index of
      negative affect showed an incidence rate ratio of 3.7 (95% confidence interval =
      2.2-6.2). The incidence rate ratios for the fourth quartile were 2.5 (95%
      confidence interval = 1.5-4.1) and 1.9 (95% confidence interval = 1.1-3.2) for
      perceived stress and stressful events, respectively. A high index of positive
      affect was associated with an incidence rate ratio of 0.6 (95% confidence
      interval = 0.3-1.0). These findings suggest that psychological stress is a risk
      factor for the common cold.

PMID- 11338316
TI  - Dermal exposure, handwashing, and hand dermatitis in the rubber manufacturing
      industry.
AB  - Skin diseases, such as hand dermatitis, are thought to be a common problem in the
      rubber manufacturing industry, as workers are exposed to a wide range of
      chemicals with known irritant and sensitizing potential. We conducted a cross
      sectional survey of a representative sample of rubber manufacturing workers (N =
      202), selected from nine different rubber companies. Prevalence of hand
      dermatitis ("major" and "minor" dermatitis) and skin injuries was assessed on the
      basis of a diagnosis by a dermatologist. We investigated the possible relations
      between actual skin exposure, handwashing practices, and hand dermatitis.
      Prevalence of major hand dermatitis (7%) was comparable with that in the general
      population; however, minor signs of dermatitis were more common among the
      surveyed population (28%), as were traumata of the skin (17%). Dermal exposure to
      cyclohexane-soluble agents at work was related to the occurrence of major hand
      dermatitis, but not to the occurrence of minor hand dermatitis. Moderate and
      frequent handwashing especially with industrial surfactants containing scrubbing
      particles were found to be strongly associated with the occurrence of minor
      dermatitis [odds ratio = 4.27 (95% confidence interval = 0.90-20.27) and odds
      ratio = 6.38 (95% confidence interval = 1.33-30.17, respectively)].

PMID- 11338317
TI  - Air pollution and birth weight in Britain in 1946.
AB  - Recent studies suggested that air pollution might be related to low birth weight.
      We tested this hypothesis on data from the British 1946 birth cohort. We found a
      strong association between birth weight and an air pollution index based on coal
      consumption. Babies born in the most polluted areas were on average 87 grams
      lighter than those born in the areas with the cleanest air. Adjustment for a
      number of sociodemographic factors did not change these estimates. While
      confounding by unmeasured factors cannot be ruled out, these historical data
      support the hypothesis that birth weight could be affected by air pollution.

PMID- 11338318
TI  - Increase of dioxin blood levels over the last 4 years in the general population
      in Spain.

PMID- 11338319
TI  - Recall of perinatal events by mothers living in rural Kenya.

PMID- 11338321
TI  - Risk of multiple primary cancers in nasal cancer patients.

PMID- 11338320
TI  - DDT spraying for malaria control and reproductive function in Mexican men.

PMID- 11338322
TI  - Is the occurrence of carpal tunnel syndrome in men underestimated?

PMID- 11338323
TI  - Applications of health services research in the treatment and prevention of
      alcohol abuse. Introduction.

PMID- 11338324
TI  - Prevention research and its actual application to health services.
AB  - The effectiveness of alcohol abuse programs, whether to treat or to prevent, is
      of major importance to health services research. Demonstrating effectiveness has
      been appropriate to establish a sound scientific basis for these programs and to
      increase public acceptance. Analysis of the costs of prevention efforts in terms
      of their demonstrated effectiveness in reducing health services demand also is
      essential. In the end, health services policy deliberations are optimally based
      on what effect is delivered for the cost of the service, not simply on a
      determination of which service is the most effective. However, in a time of
      scarce resources prevention should be studied with the same rigor as treatment in
      order to determine the best return on investment.

PMID- 11338325
TI  - The provision of services for alcohol problems: a community perspective for
      understanding access.
AB  - Alcohol use is related to numerous health and social problems. The article
      describes the prevalence of alcohol problems and dependence across a county and
      its institutions. While high rates of problem drinking were found across health,
      mental health, criminal justice, welfare, drug, and alcohol programs, the
      proportion was highest for primary health clinics, the criminal justice system,
      and welfare agencies. This also was the case when the county's most serious
      alcohol problem cases--individuals who were alcohol dependent--were examined.
      Thus it may be useful to develop screening procedures, mainstream treatment
      interventions in non-alcohol specialty agencies, and include non-specialty
      agencies in services research on access.

PMID- 11338326
TI  - Public sector managed care for substance abuse treatment: opportunities for
      health services research.
AB  - Observations of reduced utilization of alcohol and drug abuse treatment following
      the introduction of managed behavioral health care suggest that substance abuse
      services may be especially responsive to managed care restrictions and limits. In
      publicly funded treatment systems, patient attributes, system and provider
      characteristics, and financing mechanisms may heighten susceptibility to
      unintended effects. The State Substance Abuse and Mental Health Treatment Managed
      Care Evaluation Program reviewed state managed care programs for publicly funded
      alcohol and drug treatment services and is evaluating programs in Arizona, Iowa,
      Maryland, and Nebraska. The article describes initiatives and outlines evaluation
      activities. It discusses the opportunities and challenges of assessing public
      managed care plans.

PMID- 11338327
TI  - Managed care in the public sector: lessons learned from the Los Angeles PARTNERS
      program.
AB  - PARTNERS is the Los Angeles County Department of Mental Health's capitated
      managed care treatment program. To explore the context in which public sector
      managed care reforms are occurring and to understand the obstacles to
      implementing such programs, qualitative data were collected from administrators,
      case managers, and clients. Administrators were found to need assistance in
      negotiating managed care contracts and in tracking costs. Case managers, although
      concerned about increased clinical demands, enjoyed the flexibility and
      creativity their new roles allowed. Clients were satisfied with their increased
      independence, even though many had to change their site of care. Beyond
      considering these concerns, the range of community stakeholders who may be
      affected by such interventions must be addressed.

PMID- 11338328
TI  - A latent variable model of evidence-based quality improvement for substance abuse
      treatment.
AB  - Attempts to improve the quality of substance abuse treatment are hampered by an
      inability to define specifically the elements of high quality of care and, more
      important, the lack of a research paradigm within which to study the necessary
      and sufficient elements of appropriate care. This study proposes that the quality
      of-care (QOC) construct for substance abuse treatment might be best considered as
      a latent construct that does not necessarily exist as a single set of criteria
      but instead is indicated by a set of empirically derived indicators manifested as
      a latent factor. Results support defining latent QOC variables across levels of
      care for alcoholism treatment and empirically defining latent QOC measures from
      administrative records.

PMID- 11338329
TI  - A five-year population study of persons involved in the mental health and local
      correctional systems: implications for service planning.
AB  - This study investigates the relationship between recipients of mental health
      services and incarceration within local jails. The analyses showed that male and
      female recipients of mental health services are incarcerated in local jails at a
      higher rate than the general community but that most are not long-term
      incarcerations. The study further showed that the rate of incarceration for
      recipients of mental health services decreases with age but the relative risk of
      incarceration, when compared with the general population, actually increases with
      age. In addition, across all age groups female recipients of mental health
      services were found to be at greater risk of incarceration than male recipients.

PMID- 11338330
TI  - Organizational context and provider perception as determinants of mental health
      service use.
AB  - This study refines and tests an individual client model of service use and
      contrasts it with a model of service provision based on gateway provider
      perspectives. Structural equation models demonstrate that provider variables
      account for more service use variation than client variables. The client model
      accounts for 24% of the variance in service use, while the provider model
      accounts for 55% of the variance. Youth self-reported mental health was not
      positively associated with increased services or with provider perception of
      youth mental health. The provider model demonstrates the critical role played by
      provider perceptions, which are influenced more by work environment than by
      client problems.

PMID- 11338331
TI  - The health and mental health of disabled substance abusers.
AB  - In 1996 Congress terminated Supplemental Security Income (SSI) benefits to
      individuals disabled by substance abuse. Although most were expected to continue
      benefits under another disability category, 64% were not reclassified. This
      article examines data from a longitudinal study of individuals in Los Angeles
      County affected by the legislation. While poor physical health predicted both
      continued SSI benefits and receipt of public income assistance, many individuals
      reporting significant mental and physical health problems were not reclassified
      and did not receive public income assistance, raising concern for their welfare.
      Local safety nets may become increasingly important for this population.

PMID- 11338332
TI  - Rural-urban differences in service use for memory-related problems in older
      adults.
AB  - The reduced availability of providers and travel difficulties in rural areas may
      thwart older rural adults from getting the care they need for memory-related
      problems. The purpose of this study was to determine whether rural-urban
      differences exist in the probability of any service use of primary care
      physicians and mental health specialists in a full sample of older adults and in
      a subset of impaired respondents. In the full sample, rural respondents were 0.66
      times as likely (p = .06) to have used primary care physicians for memory-related
      problems compared with urban respondents. In the subgroup, rural individuals were
      0.26 times as likely (p = .02). In both groups, there were no rural-urban
      differences in the probability of mental health specialty use for memory-related
      problems. Further investigations are necessary to determine the causes.

PMID- 11338333
TI  - Random effects models for HIV marker data: practical approaches with currently
      available software.
AB  - The analysis of marker data from HIV positive patients has been the motivation
      for many new developments in applied statistics. As well as reviewing these
      methods, this paper considers the extent to which programs to implement them are
      available in current software. Particular areas of development have been the
      joint modelling of markers and survival outcomes, non-linear random effects
      models that are of particular relevance for studying the efficacy of treatments
      and the use of Bayesian computational methods for inference from marker data. The
      package WinBUGS is recommended as being particularly well suited to the analysis
      of marker data.

PMID- 11338334
TI  - Advances in medical statistics arising from the AIDS epidemic.
AB  - Many statisticians have contributed to studies of the HIV epidemic and
      progression to AIDS. They have developed new statistical methodology, where
      needed, to address HIV-related issues. The transfer of methods from one area to
      another often involves a substantial delay. This paper points to methods that
      were developed in the HIV context and have either already found applications in
      other areas of medical research or have the potential for such applications, with
      the hope that this will promote a speedier transfer of the research methods.
      Among the new tools that HIV studies have placed firmly into the pool of
      statistical methods for medical research are the methods of back-calculation,
      methods for the analysis of retrospective ascertainment data and methods of
      analysis for the combined data from clinical trials and associated longitudinal
      studies. Notions that have been stimulated substantially are use of surrogate
      endpoints in clinical trials and screening blood products by the use of pooled
      serum samples. Research activity in many other areas has been boosted
      substantially through contributions motivated by HIV/AIDS studies. Noteworthy
      examples are analyses for doubly-censored lifetime data and methods for assessing
      vaccines for transmissible diseases.

PMID- 11338335
TI  - Mathematical biology and medical statistics: contributions to the understanding
      of AIDS epidemiology.
AB  - Some of the many ways in which mathematical biology and statistics have been used
      in investigating the acquired immunodeficiency syndrome (AIDS) epidemic are
      reviewed. Aspects of the spread of the disease via social and sexual networks are
      discussed. The different kinds of data involved are critically compared. Some
      studies of the incubation period are briefly reviewed and some comments made on
      the role of adherence to therapy.

PMID- 11338336
TI  - The impact of the AIDS epidemic on medical statistics.

PMID- 11338337
TI  - Statistical advances in AIDS therapy trials.
AB  - This paper reviews recent statistical advances in HIV/AIDS therapy trials. Our
      emphasis is on three emerging areas that address key challenges in AIDS research:
      the determination of optimal treatment sequences, estimating efficacy of intended
      treatment, and inference for repeated measures with dependent censoring. A common
      theme of these topics is the use of observational data within clinical trials to
      answer questions not addressed by the conventional intent-to-treat analysis. We
      also give a brief overview of some recent contributions to other topics relevant
      to AIDS clinical trials, including modelling of treatment compliance data,
      modelling of repeated measures, and group sequential testing.

PMID- 11338338
TI  - [Vitamin C status of inhabitants of the Gomel region].
AB  - The carried out research of vitamin C status of 250 young people 17-20 years old
      constantly living in region of the periodic radioactive control of the Gomel
      region of Republic Byelorussia have shown, that in the spring the vitamin C
      deficiency is observed at more than 55% examined, and autumn this parameter is
      reduced approximately on 20%. The vitamin C provision of the women is slightly
      higher, than one of men. The vitaminization of the population within 1 month by
      polyvitaminic complexes results in twofold reduction of number examined with
      vitamin deficiency.

PMID- 11338340
TI  - [Comparative study of the effects of different sour milk products on the
      intestinal microflora of healthy infants].
AB  - Our study was aimed to investigate in comparable conditions the composition of
      intestinal microflora of healthy infants who were given 9 types of fermented milk
      products. There were observed 103 practically healthy infants aged from 4 month
      to 1,5 years old. The obtained data have shown that studied products improve
      intestinal microflora in infants. Significant increase of bifidobacteria in
      infants intestines was promoted by fermented milk products containing alive
      bifidobacteria with rather high acidity. The most of products which contain
      bifidobacteria decreased the level of hemolisinproducing Escherichia coli and
      coagulase-positive staphylococcus. The products which not contain bifidobacteria
      decreased the level of Candida albicans and protei.

PMID- 11338339
TI  - [Effects of biologically active supplements on the antioxidant and vitamin status
      of patients with hypertension and ischemic heart disease].
AB  - Biologically active additives in integrated therapy of patients with
      cardiovascular diseases against a background body overweight. The influence of
      antiaterosclerotic diet with including some biologically active additives, which
      contain vitamins C, E, B2, B6, beta-carotene, Zn, Mg, Na, K, Ca, I was studied in
      91 patients with ischemic heart disease, hypertension disease. The usage of
      biologically active additives during 4 weeks has promoted positive changes of
      clinical symptoms of diseases against a background of lowering of serum
      cholesterol, triglycerides and increasing of vitamins A, E, C, B2, B6.

PMID- 11338341
TI  - [Therapeutic and preventive nutrition].

PMID- 11338342
TI  - [Soya protein-lipid complex as a corrective agent of lipid metabolism and
      functional state in moderate hypercholesteremia].
AB  - Daily (within 28 days) persons with moderate hypercholesterinemia used in food
      flour products containing in their structure the soya protein lipide complex.
      After the specified term expiration the authentic decrease of a cholesterol, a
      hyperlipemia, low density lipoproteins and increase of high density lipoproteins
      in blood, decrease of a blood pressure, normalization of bloodstream parameters,
      decrease of a level of uneasiness and improvement of a functional state was
      marked at them.

PMID- 11338343
TI  - [Functional constipation syndrome: experience in the use of sour milk products
      and biologically active food supplements in the complex treatment of patients].
AB  - Sour milk product "Bifeedock" and biologically-active food additives of
      "Litovite" and "Pektsecom" type are used in the overall treatment of functional
      constipation and accompanying colon disbacteriosis of I and II degree. They help
      to improve the clinical symptomatics and the functional state of the
      gastrointestinal tract. According to the data analysis, the elimination of the
      colon stasis results in the improved microbiocenosis expressed in the suppression
      of growth of conditionally pathogenic microflora. It also stimulates the growth
      of the symbiotic elements of microbiota (bifidobacteria, lactobacteria and the
      intestinal E. coli).

PMID- 11338344
TI  - [Several parameters of the nutritional status of indigenous population of Far
      North].
AB  - Presented are the results of nutrition status of 803 inhabitants of Yakutia both
      sexes at the age from 20 to 50. 22 per cent of examined men and 42 per cent of
      examined women had redundant body mass. It relates to high caloric diet and
      unbalance between consumption and expense of energy. High caloric diet is a cause
      of hypercholesterinemia and hypertriglyceridemia among young and old people. The
      most part of residents had insufficiency of vitamin C and beta-carotene in
      winter. It relates to deficit of fruit and vegetables in diet. 8 per cent of
      examined men and 30 per cent of examined women had low level of hemoglobin. Thus,
      rational nutrition is necessary for prophylaxis diseases in the Far North.

PMID- 11338345
TI  - [New calcium-containing product for complex treatment of osteoporosis].
AB  - The article presents results of clinical tests of calcium-containing product--dry
      breakfast "Bodrost"--having in its composition a mineral part of bones of
      slaughter animals, on patients with menopausal and senil forms of osteoporosis. A
      chemical composition of the developed product is presented. Results of
      biochemical tests of blood and urine as well as densitometry of bones of skeleton
      of patients at the age from 50 to 80 years old are presented. It is established
      that dry breakfast "Bodrost" can be recommended for complex treatment of
      osteoporosis.

PMID- 11338346
TI  - [Current questions of sanitary supervision and control of safety of using polymer
      materials destined for contact with food products].
AB  - New directive and normative documents on state sanitary supervision of a safety
      of use of plastic of "alimentary" destination are analysed in article.

PMID- 11338347
TI  - [Thermodynamic approach to the selection of polyuronide sequestrants for the
      protection of the human body from toxic metal ions. Interactions of polyuronides
      with strontium and calcium ions].
AB  - Selectivity of polyuronide sequestrants (pectate, alginates of various uronide
      composition) in respect to Sr2+ and Ca2+ ions has been evaluated in terms of
      thermodynamic affinity. It is suggested that there is no point in the use of
      pectate as a Sr(2+)-binding agent because at initial stages of reaction it
      reveals higher affinity to Ca2+ ions in comparison to Sr2+ ions. Contrary to
      pectate, alginates under similar conditions have higher affinity to Sr2+ ions. It
      is shown that these ions are bound only by blocks of L-guluronic acid residues in
      alginate macromolecules. The results obtained lend support to the advisability of
      the use of alginate preparations with the high content of L-guluronic acid
      residues for the excretion of Sr2+ ions from human body.

PMID- 11338348
TI  - [Angiogenin content in human milk in the early period of lactation].
AB  - The content of angiogenin in human milk and dairy produce for feeding of children
      of the first year of life is investigated. It is revealed, that the highest
      concentration of angiogenin in human milk takes place in colostric period (18.00
      +/- 0.72 mg/l). During the subsequent time of lactation the concentration of
      angiogenin keeps at a level 2.00 +/- 0.06 mg/l. In products of infant's feeding
      the angiogenin either was absent, or its concentration was much lower, than in
      breast milk.

PMID- 11338349
TI  - [Dynamics of the health status of a student family].
AB  - The paper presents a comparative sociohygienic analysis of a student family over
      30 years (1970s-1990s). Particular emphasis is laid on the factors of student
      family formation, reproductive behaviour, health, medical activity, etc. that
      characterize this social group.

PMID- 11338350
TI  - [Cold shock in bacteria].
AB  - Various species and genera of bacterial show the same responses to low
      temperature. Cold induces cold shock genes, by causing significant changes in the
      regulation of protein synthesis. The synthesis of major proteins in the microbial
      cell is suppressed. However, there is synthesis of a great deal of new proteins,
      the so-called cold shock ones. The chief protein in this family is E. coli CspA
      that activates the translation of other cold shock genes and negatively regulates
      the expression of its own gene. E. coli CspA homologies were identified in many
      bacteria. They can be also identified in other microorganisms, including the
      pathogens of infectious diseases. This can be attributable to the presence of
      common antigens in different bacteria. The data presented should be borne in mind
      in identifying bacteria and in designing immunodiagnostic agents if there is a
      culture cooling stage in their technology.

PMID- 11338351
TI  - [Student health in various periods of a year from one birthday to the following
      one].
AB  - Human health varies in different seasons. There is an individual yearly health
      cycle (IYHC). The authors examined variations in working capacity (WC), stress
      inclination (SI), immunity (salivary IgA), biological age (BA), and integral
      health index (IHI) in 157 apparently healthy students in different months and
      terms of an individual year--from one birthday to the next one. SI was estimated
      by several methods. Variations in cardiac rhythm, mathematical problem solution
      induced changes in cardiac rhythm and blood pressure, colour preferences (after
      Lusher), anxiety (after Taylor) and the number of nerve rings of the iris. In
      young men, the second term of IVHC, i.e. months 4 to 6 of their birthday, was the
      best for health and the fourth term was the worst. In the last term (months 10 to
      12), the mean IHI was 30% lower than that in the second term; elevated blood
      pressure was found in 30.3% of the students, WC and salivary IgA showed the
      lowest values and SI and BA did the highest ones. In the girls, these changes
      were less pronounced and the first term was the best. The association of these
      individual yearly health variations with birth stress described by H. Lagercrantz
      and T. Slotkin (1986) is discussed.

PMID- 11338352
TI  - [Endothelium disfunction in patients with myocardial infarction at the younger
      age].
AB  - The endothelium was studied in males who had sustained myocardial infarction (MI)
      at young age (under 45 years). The parameters of endothelium-dependent dilatation
      of the brachial artery were estimated during a reactive hyperemia test and the
      blood count of circulating (desquamated) endotheliocytes was measured. The values
      obtained in patients groups randomized by different parameters were compared with
      each other and with control values. The patients who had experienced in youth
      were found to have endothelial dysfunction, as appeared as both a larger number
      of circulating blood endotheliocytes and an altered vascular response during the
      reactive hyperemia test. It was found that endothelial function was not clearly
      related to the risk factors of atherosclerosis though the association was more
      marked when coronary heart disease is concurrent with arterial hypertension and
      hypercholesterolemia.

PMID- 11338354
TI  - [Expression of the apoptosis inhibitor soluble Fas antigen in patients with
      malignant and benign bone neoplasms].
AB  - This paper presents results of comparative enzyme immunoassay of soluble serum
      Fas antigen (sFas) in 98 patients with benign and malignant bone tumors, 15
      patients with mechanical bone traumas, and 60 normal individuals of compatible
      age. The prevalence and concentration of sFas were significantly greater in
      patients with bone tumors than in normal donors and patients with mechanical bone
      traumas. The association of sFas with the pathogenesis of primary bone tumors is
      discussed in the paper.

PMID- 11338353
TI  - [Spectral analysis of the heart rate variability in various types of the left
      heart ventricle remodelling in patients with hypertension].
AB  - Autonomic cardiac regulation in different types (normal, concentric, and
      eccentric geometries) of the left ventricle (LV) was evaluated in 86 hypertensive
      patients. LV structure and function were evaluated by echocardiography). To
      calculate heart rate variability (HRV), 512 RR intervals were measured in supine
      rest and passive tilt. Power spectral analysis with fast Furrier transform was
      used to derive low- and high-frequency power spectra and the sympathovagal index
      (SVI). In the normal LV geometry group, there was a good response to the tilt
      test, by causing a 3-fold increase in SVI while in the two LV hypertrophy groups,
      the index was virtually unchanged or even decreased. The normal LV geometry group
      patients showed a positive correlation between low-frequency power and the
      relative LV wall thickness (RLVWT) while the two LV hypertrophy groups did
      increases in RLVWT and LV myocardial mass, which were associated with a reduction
      in HRV. In conclusion, HRV is significantly reduced in essential hypertension and
      is also closely connected with cardiac structure and function. Patients with
      normal LV geometry showed a preserved response to the tilt test. LVH produces
      significant autonomic regulatory disturbances possibly due to the lower
      sensitivity of cardiac adrenoceptors independently of the pattern of LV
      hypertrophy.

PMID- 11338355
TI  - [Metabolic effect of tobacco smoke and "switching" the estrogen effect: mechanism
      of increased genotoxicity].
AB  - Earlier studies demonstrated dynamic changes in the hormonal and genotoxic
      effects of estrogens and a decrease in estradiol concentrations and/or aromatase
      (estrogen synthetase) activity in the uterine tissue in rats exposed to tobacco
      smoke (TS) and in endometrial and breast tumor tissues of female smokers. This
      study was the first to reveal an elevation in the excretion of 2- and 4
      hydroxyestrogens in smoking postmenopausal women receiving estrogen-replacement
      therapy, an increase in estrogen-2-hydroxylase activity in the breast and
      endometrial tumors of the smokers, and no signs of higher aneuploidy frequency in
      the cervicovaginal epithelium of mice exposed to TS + estrogens. Thus, it can be
      concluded that there are different stages of endocrine and genotoxic effects of a
      TS + estrogen combination which may be related to the specific mechanisms and
      types of hormonal carcinogenesis. A combination of estrogens and smoking induces
      such variants of DNA damage, which are mediated mainly through the metabolism of
      catecholestrogens/free radical formation and not through increased or incorrect
      (aneuploidy) proliferation.

PMID- 11338356
TI  - [Localization of immunodominant antigens of the liver fluke Opisthorchis felineus
      by immunoelectron microscopy].
AB  - Immune electron microscopy with a panel of monoclonal antibodies to O. felineus
      antigens and human immune sera from patients was used for localization of the
      main antigens of adult O. felineus. The immune complexes at the ultrastructural
      level were visualized by 5-nm colloidal gold. The main antigens recognized by
      human antibodies and monoclonal antibodies were associated with the tegument,
      muscles, uterus, gonads, intestine and eggs of the liver fluke. The findings led
      to the conclusion that the surface structures of liver flukes stimulate a low B
      cell immune response. The structures of the excretory-secretory system of the
      parasite and their products contain a lot of main antigens and induce B-immune
      response in man.

PMID- 11338357
TI  - [Cooperation of the Russian Academy of Medical Sciences with the World Health
      Organization].
AB  - The paper presents a brief review of successful cooperation of the Russian
      Academy of Medical Sciences (RAMS) with the World Health Organization (WHO) in
      developing biomedical research and promoting the scientific bases of public
      health. This cooperation is effected in different forms. The work of 30 WHO
      collaborating centers on the basis of 18 RAMS Research Institutions plays the
      leading part in this cooperation. The paper contains specific data on the
      activities of these centers in the field of medical research, scientific
      publications, education, and training of medical staff for Russia and other
      countries. The financial support given by the WHO to its collaborating centers is
      now very limited, but scientific information, medicaments, and equipment which
      can be received by the centers from this Organization are very valuable.

PMID- 11338358
TI  - [Population health and structural changes in public health system in the Russian
      Federation in the 1990s].
AB  - The paper analyzes the structural efficiency of the therapeutical and preventive
      care system and the changes that occurred in the population's health in the
      Russian Federation in the 1990s. It shows that the reforming processes
      theoretically elaborated in detail and reflected in "The Concepts of Public
      Health and Medical Science Development in the Russian Federation" (1997) are
      slowly under way or almost absent and the structural efficiency of the entire
      therapeutical and preventive care system remains lower than it has been expected.
      The paper presents promising lines of structural and functional changes in public
      health.

PMID- 11338359
TI  - [Academic of the Academy of Medical Sciences of the USSR A. I. Strukov (on his
      100th birthday)].

PMID- 11338360
TI  - [Insufficient body weight as a death risk factor].

PMID- 11338361
TI  - [Analysis of etiology of influenza-like morbidity and monitoring influenza
      epidemic of 1998-1999 by laboratory diagnosis methods].
AB  - The etiological structure of influenza-like was analyzed in the population in
      cities and towns and in Russia as a whole in November 1998 to April 1999 by the
      findings of immunofluorescence and serological surveys of patients with acute
      respiratory viral infections (ARVI). By the results of both tests, the proportion
      of the incidence of influenza A (H3N2) was largest, the decreasing order in their
      significance was as follows: adenoviruses, type 3 parainfluenza virus, RSV,
      influenza B virus, influenza A(H1N1), types 2 and 1 parainfluenza virus. All
      influenza viruses A(H1N1) were isolated in Samara in February 1999. Three of them
      were similar to the reference strain A/Johannesburg/82/96 in antigenic
      properties, two strains appeared to be its drift variants. No A/Beijing/262/95
      (H1N1)-like viruses recommended for incorporation as part of vaccines were
      detected. All influenza A(H3N2) viruses were drift variants of strain
      A/Sydney/05/97, and all influenza B viruses were similar to the reference strain
      B/Harbin/07/94 in antigenic structure.

PMID- 11338362
TI  - Perspectives. Wanna lower health costs? Don't look to drug profits.

PMID- 11338363
TI  - "Starting life together" is key to start-up of Montana birth center. Deaconess
      Billings Clinic uses a soft touch.
AB  - Challenged by the requirements of managed care, Deaconess Billings Clinic resumed
      obstetrical services after 25 years. The resulting Family Birth Center is a
      "marketer's dream," with state-of-the-art facilities and an enviable model of
      care. The grand opening was highlighted by an open house, or "baby shower." The
      ongoing marketing campaign includes soft, sweet images of happy babies with their
      moms and dads. Memorable TV commercials emphasize the mother's comfort, the
      expertise of the medical staff, and the baby ... thoroughly enjoying the birth
      experience.

PMID- 11338364
TI  - North Memorial works for cancer. Winning campaign designed on short notice.
AB  - Gorgeous creatives, designed for North Memorial Health Care in Minnesota, prove
      effective and useful during a high-visibility fundraiser for breast cancer at
      Saks Fifth Avenue. They're recycled for later use in the hospital.

PMID- 11338365
TI  - Nature's images introduce "natural" medical campus. Woodwinds Health Campus opens
      new doors in Minnesota.
AB  - Grand opening of Woodwinds Health Campus in Minnesota combines its unique medical
      approach with well-established traditions. Everything from the design elements
      and paper to the opening day activities conforms to the interests and concerns of
      its potential market, as determined by focus groups.

PMID- 11338366
TI  - In New York, the early bird gets the holiday "plum." News releases bear fruit for
      N.Y. Weill Cornell Medical Center.
AB  - At N.Y. Weill Cornell Medical Center, the reach of media coverage is extended by
      timely news releases. Twice a year, the hospital sends out a packet of holiday
      related feature story ideas. The result is excellent coverage during the holiday
      season and an ongoing working relationship in a highly competitive market.

PMID- 11338367
TI  - Be colorful and clever ... but please don't neglect the basics!
AB  - In a time when people were born, worked and grew old in the same community, they
      knew where to find the hospitals. Our informal survey indicates that marketers
      sometimes ignore the fact that a mobile population needs clear information about
      a hospital's location.

PMID- 11338368
TI  - "Ten best" new market icon for children's hospitals. Institutions promote
      designation internally, externally.
AB  - Institutions took different approaches to the honor of being named among the 10
      best pediatric hospitals in the country. The most universal response was to
      celebrate the honor with employees through parties, banners and internal
      newsletters. Local news coverage was most welcome, too.

PMID- 11338369
TI  - Seattle hospital opens renovated children's dental clinic. Joins effort to
      promote children's oral health.
AB  - The pediatric dental clinic at Seattle's Children's Hospital and Regional Medical
      Center is filled to capacity, so marketers can invest efforts in community
      outreach and educational projects.

PMID- 11338371
TI  - Trick or treat and ho, ho, ho! Marketing campaign for Emory ER reflects the
      holiday spirit.
AB  - Emoty Healthcare, Decatur, Georgia, develops a light-hearted campaign to run
      during the fall and winter holidays, promoting its Emory Dunwoody Medical Center
      emergency room.

PMID- 11338370
TI  - Chicago's Children's Memorial Hospital uses Web site to welcome parents.
AB  - Publisher Donald E.L. Johnson lets his memories lead him back to Children's
      Memorial Hospital of Chicago. He reviews its Web site, which fills the demands of
      concerned parents, who need not only reassurance but also complete information.

PMID- 11338372
TI  - [Introduction: cloned receptors and newly developed compounds].

PMID- 11338373
TI  - [Pain, fever and prostanoids].
AB  - Although it has been known that prostanoids are involved in pain regulation and
      fever, the precise roles of their receptors and receptor subtypes are unclear.
      All prostanoid receptors have been cloned and mice deficient in each receptor
      have been developed. Recent studies using prostanoid-receptor-knockout mice are
      shedding some light on these issues. Nociceptive responses to an intraperitoneal
      injection of acetic acid and hyperalgesia induced by carrageenan were abolished
      by IP-receptor deficiency. In addition, the use of mice lacking prostanoid
      receptor is revealing an interesting role of prostanoid in neuropathic as well as
      inflammatory pain. With regard to pyrexia, PGE2 injected
      intracerebroventricularly induced the febrile response in wild-type mice, but it
      was without effect in mice lacking the EP3 receptor. Furthermore, febrile
      responses induced by IL-1 beta, an endogenous pyrogen, and LPS, an exogenous
      pyrogen, were specifically suppressed in mice lacking the EP3 receptor. These
      results indicate that PGE2 works as a common final mediator of the febrile
      response and that this action of PGE2 is mediated by the EP3 receptor. The
      determination of precise roles of prostanoids in pain and fever may provide novel
      targets for antipyretic analgesics with fewer side effects.

PMID- 11338374
TI  - [Inflammation-allergy and prostanoids. (1). Prostanoids in experimental
      inflammatory reaction].
AB  - It is known that prostaglandins (PGs) modify the inflammatory reaction in concert
      with other biologically active mediators. However, characteristics of these
      interactions or modulating actions have not yet been clarified well. Recently,
      the production of mice with specific receptor deficiencies by using the gene
      targeting procedure for PG receptors has accelerated elucidation of the roles of
      PGs through correlation of their phenotypes and experimental features. Here I
      discuss roles of PGs in experimental paw edema, the writhing reaction of a pain
      model, and regulation of cytokine production, as determined using some PG
      receptor-deficient mice. From the experiment of carrageenin-induced paw edema in
      IP receptor-deficient mice, with an indomethacin or bradykinin antagonist, we
      conclude that bradykinin initially induces paw swelling and then stimulates the
      release PGI2, which in turn enhances the swelling with bradykinin. By comparing
      the writhing responses in IP-deficient and wild-type mice, we found that PGI2 is
      a main mediator for this pain reaction. However, in the LPS-pretreated mice, not
      only PGI2 but also other PGs produced by COX-2 may be involved in pain induction.
      Production of TNF alpha and IL-10 was modified with PGI2 or PGE2; the production
      of TNF alpha was down-regulated by the stimulation via IP-, EP2- or EP4 receptor,
      but that of IL-10 was up-regulated by these receptors, resulting in an anti
      inflammatory effect.

PMID- 11338375
TI  - [Inflammation-allergy and prostanoids. (2). The role of prostanoids in allergic
      inflammation].
AB  - Allergic inflammation is orchestrated by mainly antigen-specific CD4+ T cells,
      eosinophils and mast cells, which is a characteristic feature of bronchial
      asthma, rhinitis and atopic dermatitis. Prostanoids are one of the arachidonic
      metabolites, which are produced by a variety of inflammatory cells upon
      stimulation and are thought to be involved in the pathogenesis of diseases as
      well as the regulation of homeostasis. We investigated the role of a prostanoid,
      prostaglandin D2 (PGD2), in the pathogenesis of allergic bronchial asthma using
      its receptor, DP, gene-deficient mice. We found that the disruption of the DP
      gene attenuated the allergen-induced airway eosinophilic inflammation, Th2 type
      cytokine production and bronchial hyperresponsiveness to cholinergic stimuli,
      suggesting that PGD2 is an important mediator of allergic asthma. In contrast,
      the treatment of non-steroidal anti-inflammatory agents, which are known to be
      inhibitors of cyclooxygenases, did not inhibit or instead exaggerated these
      responses in asthmatics or experimental animal models, indicating that there are
      regulatory prostanoids in allergic inflammation. Recently, strategies of gene
      manipulation such as the "knockout" or "transgenic" techniques are important
      means to understand the role of a certain functional molecule. These approaches
      and the development of their antagonists/inhibitors could help us to understand
      the function of prostanoids in the pathophysiology of allergic disorders.

PMID- 11338376
TI  - [Reproduction physiology and prostanoids].
AB  - Prostanoids, which consist of prostaglandins (PGs) and thromboxane, are produced
      from arachidonic acid by cyclooxygenases (COXs) as a rate-limiting step, and they
      exert various biological actions. Classically, prostanoids are suspected to be
      closely related to female reproductive processes such as ovulation, luteolysis
      and uterine contraction, as well as pathological processes such as fever
      generation and pain modulation. Recently the cDNA cloning of a series of
      prostaglandin-synthesizing enzymes and receptors enabled us to clarify which
      isoform or subtype is involved in each reproductive process by generating
      individual gene-deficient mice. In late pregnancy, PGF2 alpha synthesized by COX
      1 is essential for induction of parturition via luteolysis. Furthermore, impaired
      induction of COX-2 in the myometrium of PGF2 alpha receptor-deficient mice is
      accompanied with loss of parturition, suggesting that COX-2 is presumably
      responsible for producing uterotonic PGs. In early pregnancy, PGE2 synthesized by
      COX-2 induces the expansion of cumulus cells through EP2 receptor and contributes
      to ovulation and fertilization. These results may be useful in not only
      developing novel drugs in the reproductive area but also understanding and
      overcoming harmful reproductive side effects of classical and novel drugs in non
      reproductive areas.

PMID- 11338377
TI  - [Gastrointestinal cytoprotection by prostaglandin E and EP receptor subtypes].
AB  - Endogenous prostaglandins (PGs) play important roles in modulating the mucosal
      integrity and various functions of the gastrointestinal tract. Among them, E-type
      PGs are most effective in these actions. This article reviews recent studies
      dealing with the relationship of the cytoprotective action of PGE2- and EP
      receptor subtypes in the gastrointestinal mucosa. PGE2 exerts gastric
      cytoprotection against HCl/ethanol and indomethacin. These effects were mimicked
      by only EP1 agonists and attenuated by EP1 antagonists. Likewise, the adaptive
      cytoprotection induced by a mild irritant was attenuated by EP1 antagonists as
      well as indomethacin. On the other hand, the protective effect of dmPGE2 against
      indomethacin-induced small intestinal lesions was mimicked by only EP3 and EP4
      agonists. Similar results were obtained in EP-receptor knockout mice; i.e., PGE2
      failed to exhibit both direct and adaptive cytoprotection in EP1-receptor
      knockout mice, while the protective action in both the duodenum and small
      intestine was hampered in EP3-receptor knockout mice. The underlying mechanism
      related to these actions of PGE2 in the stomach, duodenum or small intestine may
      be related to inhibition of stomach contraction, stimulation of duodenal alkaline
      secretion, or suppression of bacterial translocation due to inhibition of
      intestinal contraction as well as stimulation of mucus secretion, respectively.

PMID- 11338378
TI  - [Endogenous prostaglandins and angiogenesis].
AB  - Angiogenesis is a process involved in several physiological events including
      embryonic development, female reproductive cycle placentation and wound repair.
      It also plays a part in various pathological conditions such as tumor growth,
      diabetic retinopathy and rheumatoid arthritis. Angiogenesis is a very complex
      multistep process involving a variety of biologically active substances, among
      which are the prostaglandins (PGs), which can induce several growth factors and
      proliferation of endothelial cells in vitro and in vivo. Angiogenesis is
      reportedly enhanced by prostaglandins (PGs). We investigated whether or not COX-2
      mediated angiogenesis in chronic and proliferate granuloma. In rat sponge
      implants, angiogenesis was gradually developed over a 14-day experimental period
      as granuloma formed. In sponge granuloma, mRNA of COX-1 was constitutively
      expressed, whereas that of COX-2 was increased with neovascularization in
      parallel with the increased expression of vascular endothelial growth factor
      (VEGF). bFGF-stimulated angiogenesis was inhibited by indomethacin or a selective
      COX-2 inhibitor, NS-398. These results suggested that endogenous PGs generated
      through COX-2 may enhance the neovascularization in sponge granuloma by increased
      expression of VEGF and that a COX-2 inhibitor would facilitate the management of
      conditions involving angiogenesis.

PMID- 11338379
TI  - [Role of EP4 receptor in bone resorption induced by PGE].
AB  - Prostaglandin E2 (PGE2) acts as a potent stimulator of bone resorption. We
      examined PGE2-induced bone resorption using mice lacking each subtype (EP1, EP2,
      EP3 and EP4) of PGE receptor and identified the PGE receptor subtype(s) mediating
      PGE2 action. In calvarial culture from EP1-, EP2-, and EP3- knockout mice, PGE2
      stimulated bone resorption to a similar extent to that found in calvaria from the
      wild-type mice. On the other hand, a marked reduction in bone resorption in
      response to PGE2 was found in the calvarial culture from EP4-knockout/mice.
      DbcAMP greatly stimulated bone resorption similarly in both wild-type and EP4
      knockout mice. In mouse calvarial cultures, EP4-agonist markedly stimulated bone
      resorption, but its maximal stimulation was less than that induced by PGE2. EP2
      agonist also stimulated bone resorption, but only slightly, EP1- and EP3-agonists
      did not stimulate it at all. These findings suggest that PGE2 stimulates bone
      resorption by a mechanism involving cAMP, which is mediated mainly by EP4 and
      partially by EP2.

PMID- 11338380
TI  - [Gene therapy: current status and promise].
AB  - As of summer 2000, more than 400 protocols developed for human gene therapy have
      been reported, and there have been recent successful applications in some
      diseases such as arteriosclerosis obliterance, immunodeficiency X-1 (SCID-X1) and
      hemophilia B. However, complications have also occurred. Successful gene therapy
      is dependent on the development of an effective gene delivery system. One
      approach is development of chimeric vector systems that combine at least two
      different vector systems. However, a perfect vector system has not yet been
      constructed. Difficulties of in vivo gene transfer appear to result from
      resistance of living cells to invasion by foreign materials and from interference
      of cellular functions. We should reevaluate what barriers in tissues affect in
      vivo gene transfection and how to solve these problems for gene therapy.
      Moreover, in Japan, there should be more extensive preparation of social systems
      to promote clinical trials based on basic research.

PMID- 11338381
TI  - The emergence and dissemination of whitefly-transmitted geminiviruses in Latin
      America.
AB  - The proliferation and rapid dissemination of whitefly-transmitted viruses of
      important food and industrial crops in Latin America, have been the consequence
      of drastic changes in traditional cropping systems. Some of the expanding non
      traditional cash and export crops, such as soybean and several vegetables, have
      served as suitable reproductive hosts for the whitefly Bemisia tabaci. This
      insect pest has been shown to transmit at least 20 different geminiviruses that
      affect different commercial and basic food crops in Latin America. This review
      summarizes the existing knowledge on this important group of viruses and their
      vector in this region.

PMID- 11338382
TI  - Molecular characterization of human astroviruses in Germany.
AB  - The molecular epidemiology of human astroviruses (HAstV) was studied using fecal
      specimens from different regions in Germany during 1998/99 by RT-PCR and
      sequencing of ORF2 amplicons. HAstV of genotypes 1-4 were found to cocirculate in
      Germany. The complete sequence of one isolate representing genogroup 3 (putative
      serotype 3) was determined.

PMID- 11338383
TI  - Genetic variability of respiratory syncytial virus subgroup B strain isolated
      during the last 20 years from the same region in Japan: existence of time
      dependent linear genetic drifts.
AB  - The genetic variability of 32 respiratory syncytial virus (RSV) sub-group B
      isolates from a single community in Japan during the 20 years from 1980 to 1999
      was determined. Two variable regions of the attachment (G) protein gene were
      amplified by reverse transcriptase-polymerase chain reaction amplification and
      their products were sequenced directly. Phylogenetic analysis of nucleotide
      sequences revealed seven distinct branches in which strains isolated during
      seasons of close proximity were located: however, isolates from the same season
      were often in plural branches. There was a tendency for recent isolates to lie at
      the end of each branch and these linear evolutionary changes were typically
      represented in a branch containing nine strains isolated during 6 seasons from
      '80 to '86. Three kinds of usages of stop codons were confirmed and isolates
      located in each branch used the same stop codons. These observations suggest that
      there are multiple subgroup B lineages co-circulating and that each lineage
      strain may exhibit linear evolutionary genetic drifts in order to survive over
      successive epidemics within the same population, although it has a conserved
      uniform G protein length with the use of the same stop codon.

PMID- 11338384
TI  - The readthrough region of Potato mop-top virus (PMTV) coat protein encoding RNA,
      the second largest RNA of PMTV genome, undergoes structural changes in naturally
      infected and experimentally inoculated plants.
AB  - Molecular data on Potato mop-top virus (PMTV), genus Pomovirus, is currently
      mostly based on analysis of two Scottish isolates, PMTV-S and PMTV-T. Here we
      report the complete sequence of "the coat protein (CP) encoding RNA" of an
      isolate of PMTV obtained from the field in Sweden. Our data show that this RNA
      (3134 nt) is the second largest of the three RNA species in the tripartite PMTV
      genome, and it should, therefore, be referred to as RNA 2. This nomenclature is
      consistent with other pomoviruses. The sequence of the readthrough domain (RT) of
      RNA 2 was determined also in two additional field isolates of PMTV from Finland
      and Denmark. All three isolates contained a novel, 109 nucleotides long sequence
      at the 3'-end of the RT, which has not been found in PMTV-S and PMTV-T. Hence,
      our data suggest that the RNA 2 sequences previously described for the isolates
      PMTV-T and PMTV-S may represent deletion derivatives. The C-proximal half of RT
      contained many amino acid (aa) differences among the isolates, in contrast to
      only few aa differences in the N-proximal part of RT. Deletion variants of RNA 2
      were generated from the Nordic isolates in potato tubers infected in the field,
      and in the mechanically inoculated test plants. All deletions started within a
      short region (18 nt) and removed 558-940 nt from the 3'-end of RT region. This
      study for the first time describes the full-length sequence of the "CP-encoding
      RNA" (RNA2) of PMTV, and reveals considerable aa variability and occurrence of
      deletion variants of RT in the field isolates of PMTV.

PMID- 11338385
TI  - Detection and molecular characterization of cultivable caliciviruses from
      clinically normal mink and enteric caliciviruses associated with diarrhea in
      mink.
AB  - Enteric caliciviruses are emerging pathogens responsible for diarrhea or
      gastroenteritis in their respective hosts. In this report, mink enteric
      caliciviruses (MEC) were detected in feces from diarrheic mink by both immune
      electron microscopy (IEM) and RT-PCR using a broadly reactive primer pair
      (p289/290) targeting the highly conserved RNA polymerase regions of the enteric
      caliciviruses, Norwalk-like viruses (NLVs) and Sapporo-like viruses (SLVs). The
      MEC possess classical caliciviral morphology with typical cup-shaped depressions
      on the viral surface. Sequence analyses based on nucleotide and predicted amino
      acid (aa) sequences of the RT-PCR products indicated that MEC is most closely
      related genetically to SLVs of humans and animals. The MEC shared the highest aa
      identities (64-71%) in the RNA polymerase region with both human SLVs and the
      porcine enteric calicivirus (PEC) Cowden strain SLV, indicating that MEC may
      belong to an individual genogroup or subgroup in the SLV genus. The MEC shared
      only limited aa identities in the RNA polymerase region with vesiviruses (40-51%)
      and NLVs (29-33%). The RNA polymerase regions of the cultivable, non-enteric mink
      caliciviruses (MCV) were also amplified by RT-PCR using the primer pair Pol1/Pol3
      based on sequences of vesiviruses, and the primer pair p289/290. Sequence
      analysis indicated that these MCV shared higher aa identities in the RNA
      polymerase region with vesiviruses (58-81%) than with SLVs (43-51%) including the
      MEC, lagoviruses (35-37%) and NLVs (27-35%), suggesting that they are most
      closely related genetically to vesiviruses. The MEC associated with diarrhea in
      mink are morphologically similar to but are genetically distinct from the
      cultivable MCV and likely represent a new member of the SLV genus.

PMID- 11338386
TI  - An element downstream of the transcription start site is required for activation
      of Bombyx mori nucleopolyhedrovirus bro-c promoter.
AB  - Bombyx mori nucleopolyhedrovirus (BmNPV) contains five baculovirus repeated ORF
      (bro) genes. We have previously reported that all of these genes (bro-a, b, c, d
      and e) are transcribed as early genes and require viral factor(s) for their
      expression. In this study, we investigated the mechanism of promoter activation
      of the bro-c gene. Transient expression assays using genomic libraries of BmNPV
      indicated that the baculoviral trans-regulator IE-1 is responsible for activating
      the bro-c promoter. To identify essential site(s) for promoter activation,
      mutations were introduced to the promoter region of bro-c. Interestingly, it was
      shown that the pentanucleotide sequence CACGC located 30 nucleotides downstream
      of the RNA start site was essential for bro-c promoter activation. In addition,
      the RNA start site and the spacing between the RNA start site and CACGC were also
      required for promoter activation. By introducing a CACGC sequence into the
      corresponding region of the bro-b promoter, which is not normally trans-activated
      by IE-1, we demonstrated that this pentanucleotide motif has the ability to
      confer trans-activation by IE-1 on a promoter. Gel retardation experiments also
      showed a sequence-specific DNA binding protein induced by baculovirus infection
      interacts with the CACGC motif.

PMID- 11338387
TI  - Expression of receptor for ecotropic murine leukemia virus on hematopoietic
      cells.
AB  - A fusion protein (F-SU/GFP) which is comprised of the surface (SU) subunit of the
      Friend MuLV envelope glycoprotein and the green fluorescence protein (GFP) was
      generated by a baculovirus expression system. The F-SU/GFP specifically bound to
      mammalian tissue cultured cells expressing the mCAT-1, the receptor for ecotropic
      murine leukemia virus (ECO-MuLV). The expression level of mCAT-1 on hematopoietic
      cells was measured based on the capacity of cells to absorb the F-SU/GFP. In
      BALB/c mice susceptible to Eco-MuLV infection, all hematopoietic cell
      subpopulations absorbed the F-SU/GFP with the most prominent absorption observed
      in the TER119+ erythroblasts. Hematopoietic cells from C4W and AKR mice did not
      absorb the F-SU/GFP as readily as the BALB/c cells, probably due to expression of
      the envelope glycoproteins of endogenous Eco-MuLVs in these mice. Although AKR
      mice are susceptible to Eco-MuLV infection while C4W mice are resistant, these
      mice showed no apparent difference in the F-SU/GFP-absorbing capacity.

PMID- 11338389
TI  - Inhibition of porcine reproductive and respiratory syndrome virus by interferon
      gamma and recovery of virus replication with 2-aminopurine.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) belongs to a group of
      RNA viruses that establish persistent infections. A proposed strategy for evading
      immunity during persistent PRRSV infection is by preventing the induction of IFN
      activity in pigs and/or by blocking the activation of antiviral proteins in
      permissive cells. IFN-gamma mRNA expression was observed in the lymph nodes and
      lungs of pigs infected with wild-type PRRSV strain SDSU-23983. Pretreatment of
      MARC-145 cells with IFN-gamma inhibited wild-type (SDSU-23983 P6) and culture
      adapted (SDSU-23983 P136) PRRS viruses in a dose-dependent manner and at
      relatively low concentrations. The effect of IFN-gamma on virus replication
      included reductions in the number of infected cells, virus yield, and RNA content
      in single cells. Virus replication was partially restored by the addition of 2
      aminopurine (2-AP), an inhibitor of dsRNA inducible protein kinase (PKR). The
      addition of 2-AP also restored the viral RNA content per cell to near normal
      levels, suggesting that inhibition of viral RNA synthesis was through PKR. The
      principal difference between P6 and P136 isolates was the recovery of P136
      replication with lower concentrations of 2-AP. Immunostaining with anti-PKR
      antibody showed a redistribution of PKR from the cytoplasm into nucleoli of
      infected cells.

PMID- 11338388
TI  - Molecular epidemiology of echovirus 30 in Europe: succession of dominant
      sublineages within a single major genotype.
AB  - The genetic relationships between 131 echovirus type 30 (E-30) field isolates
      were studied using phylogenetic analysis of three genomic intervals: VP4/VP2 (420
      nt), the entire VP1 and VP1/2A (150 nt). The strains had been isolated between
      1975-1998, in different European countries, and in Israel and Japan. The maximum
      genetic variation was 15.7% in the VP4/VP2 region, 21.3% across the VP1/2A
      junction and 16.7% in the VP1-gene. The clustering patterns were very similar in
      all three regions. Two distinct genotypes were observed among the European
      strains, one of which was prevailing, spanning most of the investigated period.
      The same genotype was previously described to be the most prevalent circulating
      lineage of E-30 in Northern America. Interestingly, the two other genotypes
      comprising the prototype strain Bastianni and the oldest European isolates
      circulating before 1976, respectively, had apparently disappeared. Furthermore,
      the oldest lineages of the prevailing genotype had likewise disappeared and the
      recently isolated strains in the prevailing genotype were genetically quite
      homogeneous, even when isolated in geographic regions far apart. These results
      indicate that the genetic variability of echovirus 30 is significantly lower than
      that of other previously characterized enteroviruses. Furthermore, one single,
      major genotype showed epidemic spread across two continents. Interestingly,
      despite the low nucleotide variability, maximum amino acid sequence variability
      in VP1 was surprisingly high, 8.0%, suggesting possible antigenical differences.

PMID- 11338390
TI  - Direct evidence for genome segment reassortment between concurrently-circulating
      human rotavirus strains.
AB  - Extensive heterogeneity in electropherotypes observed among group A human
      rotaviruses has been considered as a result of two major mechanisms; i.e., the
      accumulation of point mutations and genetic reassortment between concurrently
      circulating strains. However, no evidence was reported thus far indicating that
      any one of field isolates of rotavirus was formed by direct reassortment of
      concurrently circulating two parental strains. Comparison of the genome of human
      rotavirus specimens collected over a six year period by electropherotyping and by
      the sequencing of selected gene segments identified two reassortants that were
      generated in nature between strains circulating co-dominantly in the same
      epidemic season. This is the first report directly showing that at least some
      part of electrophoretic diversity observed among rotavirus strains was explained
      by genetic reassortment between strains concurrently circulating in the human
      population. This supports the hypothesis that genetic reassortment among co
      circulating strains operates as a key mechanism for the genetic variability of
      rotaviruses in nature.

PMID- 11338391
TI  - Natural minus-strand RNAs of alfalfa mosaic virus as in vitro templates for viral
      RNA polymerase. 3'-terminal non-coded guanosine and coat protein are insufficient
      factors for full-size plus-strand synthesis.
AB  - Replication complexes of alfalfa mosaic virus produce in vivo large quantities of
      plus-strand RNAs, but this production is fully dependent on the presence of coat
      protein. In order to study this process of RNA-dependent and coat protein
      regulated RNA synthesis we have isolated the three natural minus-strand RNAs
      (containing any posttranscriptional modification that might have occurred) and
      have tested them for coat protein binding sites and template activity in an in
      vitro system with the viral RNA polymerase. The enzyme was prepared by an
      advanced isolation procedure. All three minus strands had a single non-coded G at
      their 3' terminus. They were not able to withdraw coat protein subunits from
      virions as free virion RNAs do. No sites protected by coat protein against
      ribonuclease T1 degradation were found. Two large T1 oligonucleotides from minus
      RNA 1 and one from minus RNA 3 were bound by coat protein to Millipore filters.
      Except for minus RNA 3 which caused a minute amount of full-size plus strand to
      be synthesized, the minus strands did not function as templates for full-size
      complementary strands. On the other hand, they gave rise to a number of well
      defined shorter products, the synthesis of which was stimulated by the addition
      of coat protein. These products could not be elongated by a chase treatment and
      were probably the result of internal initiations. It is concluded that, although
      posttranscriptional modifications of the template and the presence of coat
      protein may be necessary factors for plus-strand RNA synthesis, they are
      certainly not sufficient. Our purified in vitro system needs further
      sophistication.

PMID- 11338392
TI  - Molecular epidemiology of enterovirus 71 in Taiwan.
AB  - Taiwan suffered a severe and widespread outbreak of enterovirus infection in
      1998. More than 400 children were hospitalized, with seventy-eight fatalities due
      to central nerve system (CNS) involvement and cardiopulmonary collapse.
      Enterovirus 71 (EV71) was incriminated as the causative agent for the fatal
      cases. To understand the viral molecular epidemiology in this outbreak, fragments
      of 207-bp length of the VP4 region in 23 Taiwanese EV 71 isolates were sequenced.
      Pair-wise comparison revealed a 17.5-24.4% difference between the isolates and
      the prototype BrCr. However, all the changes in the VP4 region of the isolated
      strains were synonymous substitutions. Phylogenetic analysis was performed on
      these 23 isolates and 21 others deposited in GenBank. In this study, forty-four
      EV71 isolates from the world were separated into three distinct genotypes: A, B
      and C. The EV71 prototype strain, BrCr/70, is the only strain of genotype A.
      Group B included strains from the United States, Japan and Taiwan. Most strains
      in genotype B were isolated prior to 1990. Group C consisted of strains from
      Japan and Taiwan. Most strains of genotype C were isolated after 1990, they were
      further divided into 3 clusters: i.e. C-1, C-2 and C-3. In Taiwan, two genotypes,
      B and C-3, were co-circulating during the outbreak in 1998, although a minor
      group of genotype B may have appeared in Taiwan before 1986. The majority of the
      isolates clustered in genotype C-3. Genotype C showed a higher evolutionary rate
      than genotype B (3.9 x 10(-3) vs. 1.4 x 10(-3)) in the VP4 region. There seems to
      be a worldwide trend with strains of genotype B appearing earlier than strains of
      genotype C which took over later in the dominance.

PMID- 11338393
TI  - Effects of a second intron on recombinant MFG retroviral vector.
AB  - The retroviral vectors based on an MFG-type backbone have superior expression
      characteristics, in part, due to the presence of the retroviral chimeric intron
      (MFG intron). We tested the hypothesis that inclusion of a second intron in MFG
      vectors may influence packaging and/or LTR-driven transgene expression. We
      constructed two MFG retroviral vectors, MFG/hFIXc and MFG/hFIXm2, containing
      human factor IX (hFIX) cDNA without and with a 0.3-kb hFIX intron, respectively.
      When tested with primary mouse myoblasts or HepG2 cells in culture for transient
      expression activity, pMFG/hFIXm2 plasmid produced two-to-three fold higher hFIX
      than pMFG/hFIXc. These vectors produced equivalent retroviral titers from
      packaging cells. In transduced cells, the splicing of the MFG intron in the
      retroviral transcripts occurred at a similar efficiency; however, MFG/hFIXc virus
      gave two-fold higher hFIX expression than that of the MFG/hFIXm2 viral infection.
      Analyses of MFG/hFIXm2 virion RNA and transduced cell genomic DNA suggested that,
      although the hFIX intron containing viral RNA are packaged, these viruses fail to
      integrate their transgenes into the genome of transduced cells, suggesting a
      block at the reverse transcription and/or integration steps. Similar results were
      also obtained with the prototype vectors, LIXcSN and LIXm2SN, lacking the MFG
      intron. Together, these results suggest that a hFIX cDNA sequence in the
      retroviral vectors performs better over hFIX intron-containing minigene.

PMID- 11338394
TI  - Nucleotide sequence comparison of the 3' terminal region of the genome of pepper
      vein mottle virus isolates from Tunisia and Ivory Coast.
AB  - Three Tunisian PVMV isolates identified in pepper and tomato fields and one
      isolate from Ivory Coast were submitted to biological and molecular analysis.
      Phenotypically, Tunisian isolates induced mild symptoms while the Ivory Coast one
      is more aggressive on tobacco. As no PVMV sequence data are available, detailed
      sequence comparisons of coat protein gene (CP) were made. No nucleotide or amino
      acid changes in this region could be related to the pathogenicity of the isolates
      analysed. With the aim to increase our molecular understanding of the biological
      properties, we have sequenced the 3'-non translated region (3'NTR). Results
      suggest that this region of the RNA genome may be involved in the modulation of
      disease symptoms.

PMID- 11338395
TI  - Contributions of genetic drift and negative selection on the evolution of three
      strains of wheat streak mosaic tritimovirus.
AB  - Genome sequences of three Wheat streak mosaic virus (WSMV) strains were compared.
      The Type and Sidney 81 strains of WSMV from the American Great Plains were
      closely related, with sequence identities of 97.6% (nucleotide) and 98.7% (amino
      acid). In contrast, the El Batan 3 strain from central Mexico was divergent, and
      shared only 79.2-79.3% (nucleotide) and 90.3-90.5% (amino acid) sequence identity
      with Type and Sidney 81. All three WSMV strains were serologically related,
      however the El Batan 3 capsid protein (CP) had 15 fewer amino acid residues.
      Phylogenetic analysis of the CP cistron indicated that Type, Sidney 81, and nine
      other American isolates of WSMV were closely related and distinct from the El
      Batan 3 sequence. Nucleotide substitutions among the WSMV strains were not
      randomly distributed across the genome with more variation within P1, HC-Pro, and
      CP, and less within P3. One 400-nucleotide region of the genome, corresponding to
      the 3'-end of P3, was strikingly deficient in silent substitutions. Nonetheless,
      the ratio of synonymous to non-synonymous substitutions throughout the genome was
      essentially the same for all three WSMV strains. Collectively, our data indicate
      that both genetic drift and negative selection have contributed to the evolution
      of WSMV strains.

PMID- 11338396
TI  - Nitric oxide biphasically modulates GH secretion in cultured cells of GH
      secreting human pituitary adenomas.
AB  - BACKGROUND: Nitric oxide (NO) biphasically modulates osteoclast function, sperm
      motility and testosterone production by exerting a positive effect at low
      concentrations and a negative effect at high concentrations. In this study the
      effect due to administration of four NO-donors, each releasing an individual
      amount of NO, was studied on GH secretion from human adenomatous GH-secreting
      cells. METHODS: Sodium nitroprusside (SNP), diethylenetriamine NO adduct
      (DETA/NO), diethylamine/NO complex sodium salt (DEA/NO), and S-nitroso-N
      acetylpenicillamine (SNAP) were administered at a concentration of 10-4 M to
      cells isolated after transsphenoidal adenomectomy from five acromegalic patients.
      RESULTS: SNP significantly (p < 0.01) increased GH secretion, while the other NO
      donors inhibited GH secretion in comparision with the amount of GH spontaneously
      released by unstimulated cells. Each drug showed an individual degree of
      inhibitory potency: DEA/NO > DETA/NO > SNAP. Nitrite accumulation in the media
      was measured as a marker of NO released by each individual drug and was found to
      be different for each drug (DEA/NO > DETA/NO > SNAP > SNP). A negative
      correlation (R = -0.93; p < 0.05) was found between nitrite release and GH
      secretion induced by each drug. CONCLUSIONS: These data show that low and quasi
      physiological levels of NO, such as those released by SNP, stimulate GH
      secretion, while high NO levels, such as those released by the other NO-donors,
      inhibit GH secretion. Thus, NO is shown to be able to modulate GH secretion in a
      dose-dependent manner in GH adenomatous cells from human pituitary adenomas.

PMID- 11338397
TI  - [Attitudes toward insulin prescription in type 2 diabetic patients non-compliant
      with diet therapy].
AB  - BACKGROUND: Investigate the compliance of type 2 diabetic patients with the
      prescription of insulin according to pre-existing ideas on insulin, and to
      personality traits. METHODS: Twenty insulin-treated type 2 diabetic patients were
      selected on the basis of previous scarce compliance with diet and exercise and
      BMI > 28 kg/m2. The patients' attitudes toward insulin prescription were
      evaluated with a semi-structured interview and personality traits were evaluated
      with the ACL test(Adjective Check List). RESULTS: When insulin was first
      prescribed to these patients, 65% accepted immediately. However, 45% answered
      that their acquiescence to insulin treatment was accompanied by doubts or
      apprehension. The fear of insulin dependence was shared by 50%, with a much
      greater prevalence among those who resisted to insulin treatment (86% vs 31%) and
      those who recalled doubts and fears about insulin (73% vs 22%). Patients with a
      fear of dependence differed significantly from the others in five personality
      scales: greater opposition and ambiguity, less self-confidence, more inflexible,
      less demanding of others and more inclined to bargain. CONCLUSIONS: The
      irrational fear of dependence may, therefore, play a role in both the manifest
      acceptance/rejection of insulin and non-expressed doubts, and may in turn be
      influenced by personality traits. Specific patient education on insulin treatment
      in type 2 diabetes is necessary, and should be planned according to the
      personality factors that may influence the perception of facts and the patients'
      motivation.

PMID- 11338398
TI  - Exogenous glucocorticoids affect in different way the various phases of bone
      formation in postmenopausal patients.
AB  - BACKGROUND: To determine the effect of glucocorticoid excess on the most
      important circulating markers of bone formation in postmenopausal treated
      patients. METHODS: The study included 15 postmenopausal women taking
      glucocorticoids for various medical conditions and two groups of 30 healthy
      premenopausal and 28 age-matched postmenopausal women as controls. Osteoblastic
      activity was assessed by measuring both serum levels of osteocalcin (BGP) (N-tact
      Osteo SP, Incstar Co.) and the bone-specific isoenzyme of alkaline phosphatase
      (BAP) (Alkphase-B, Metra Biosystems). RESULTS: The mean values of serum BGP found
      in patients taking steroids were significantly reduced as compared to those found
      in both fertile and postmenopausal women (p < 0.0001). The mean serum levels of
      BAP were significantly increased in treated patients as compared to premenopausal
      women (p < 0.0001), while no significant difference was found between patients
      and age-matched postmenopausal women. Similar results were also obtained when
      individual values of both serum BAP and BGP were expressed as standard units in
      comparison to values obtained in fertile subjects (T-score) or postmenopausal
      subjects (Z-score). CONCLUSIONS: Steroid therapy in postmenopausal patients
      differentially affects the various phases of bone formation. Measurement of serum
      BGP may represent a reliable parameter for monitoring bone formation in
      postmenopausal treated patients.

PMID- 11338399
TI  - Medullary thyroid carcinoma. Natural history and surgical treatment.
AB  - In the present review the Author examines the natural history, clinical aspects,
      diagnostic aspects and surgical treatment representing the therapy for medullary
      thyroid carcinoma (MTC), with particular stress on the recommendation that a
      meticulous total thyroidectomy is always indicated, without leaving any residual
      thyroid gland tissue. Lymphadenectomy of the central part of neck is also
      recommended, with the abstraction of the jugular chain lymph nodes. In the case
      of positivity of one of those lymph nodes, it is necessary to perform a
      functional cervico-mediastinic lymphadenectomy.

PMID- 11338400
TI  - Anaplastic thyroid carcinoma in a 49 year-old woman with a long-standing goiter.
      A case report.
AB  - A 49 year-old woman with anaplastic thyroid carcinoma came, for the first time,
      to our clinic with an enlarged supraclavicular lymph node. Ten years earlier she
      received a diagnosis of benign nodular goiter and has been followed up with
      ultrasonography, which never demonstrated any enlargement of her thyroid nodule
      and with fine needle aspiration biopsies (FNAB), that always proved normal. An
      ultrasonographic control, performed 10 months before diagnosis, showed the onset
      of a shell calcification all around the thyroid nodule that forbade the
      performance of FNAB. At initial examination in our endocrinology centre she was
      found to have an enlarged thyroid nodule (changing from 3.5 cm to 4.5 cm) and a
      supraclavicular lymph node 3 cm wide. The patient was therefore sent to the
      surgeon who performed a total thyroidectomy and a lymph node exenteration. The
      histological examination reported a thyroid anaplastic carcinoma, composed of
      osteoclast-like cells and large calcifications, which showed signs of local
      invasion and vessel infiltration; the supraclavicular lymph node proved to be a
      large metastasis of anaplastic thyroid cancer. Total body CT scan, bone
      scintigraphy and brain CT scan showed, respectively, lung, bone and brain
      metastasis. Postoperative chemotherapy was rapidly interrupted for acute
      toxicity. The patient died for lung, bone and brain metastasis, 2 months after
      initial examination.

PMID- 11338402
TI  - Comparison between seasons of the ultraviolet environment in the shade of trees
      in Australia.
AB  - BACKGROUND/PURPOSE: This paper has considered the erythemal UV (UVery), UVA and
      visible irradiances in the shade of Australian trees for each season at a sub
      tropical southern hemisphere site. METHODS: The irradiances in tree shade have
      been measured with radiometers as a percentage of the irradiances in the sun for
      each season of the year. RESULTS: Although the solar irradiances are lower in
      winter, the percentages of the UV in tree shade compared to the UV in full sun
      are marginally higher (by up to 7%) in the winter compared to summer. The range
      of percentages for UVery was up to double that of the percentages of the visible
      waveband. The percentages for UVery were also higher than for the UVA waveband.
      The percentages of the irradiances in the tree shade compared to full sun are 8
      14% lower at noon compared to the morning and afternoon for the UVery waveband.
      The ratio of UVA to UVery is lower in the tree shade compared to the full sun.
      CONCLUSIONS: The UVA to UVery ratio is expected to be even lower in the tree
      shade as a result of ozone depletion. This, combined with the visible irradiances
      in the tree shade not being a reliable indication of the biologically damaging UV
      irradiances, has consequences for public health and skin cancer prevention.

PMID- 11338401
TI  - Xeroderma pigmentosum--bridging a gap between clinic and laboratory.
AB  - Xeroderma pigmentosum (XP) is an autosomal recessive photosensitive disorder with
      an extremely high incidence of UV-related skin cancers associated with impaired
      ability to repair UV-induced DNA damage. There are seven nucleotide excision
      repair (NER) complementation groups (A through G) and an NER proficient form (XP
      variant). XPA, B, D and G patients may also develop XP neurological disease. The
      laboratory diagnosis of XP can be performed by autoradiography. Recently, the
      isolation and characterization of the genes responsible for XP have made it
      possible to use molecular biological techniques to diagnose XP patients, for
      carrier detection and for prenatal diagnosis, especially in Japanese XPA
      patients. These techniques include polymerase chain reaction (PCR) and plasmid
      host cell reactivation assays with cloned XP genes. DNA damage is not repaired by
      the NER system equally throughout the genome. There are two DNA repair pathways:
      1) transcription-coupled repair, and 2) global genome repair. Many factors
      involved in these pathways are related to the pathogenesis of XP and a related
      photosensitive disease, Cockayne syndrome. Clinical management consists of early
      diagnosis followed by a rigorous program of sun protection including avoidance of
      unnecessary UV exposure, wearing UV blocking clothing, and use of sunblocks on
      the skin. Although there is no cure for XP, the efficacy of oral retinoids for
      the prevention of new skin cancers, local injection of interferon, and the
      external use of a prokaryotic DNA repair enzyme have been reported.

PMID- 11338403
TI  - Comparison of three techniques for evaluating skin erythemal response for
      determination of sun protection factors of sunscreens: high resolution laser
      Doppler imaging, colorimetry and visual scoring.
AB  - BACKGROUND/PURPOSE: Sun protection factor (SPF) measurement is based on the
      determination of the minimal erythema dose (MED). The ratio of doses required to
      induce a minimal erythema between product-treated and untreated skin is defined
      as SPF. The aim of this study was to validate the conventionally used visual
      scoring with two non-invasive methods: high resolution laser Doppler imaging (HR
      LDI) and colorimetry. Another goal was to check whether suberythemal reactions
      could be detected by means of HR-LDI measurements. MATERIALS AND METHODS: Four
      sunscreens were selected. The measurements were made on the back of 10 subjects.
      A solar simulator SU 5000 (m.u.t., Wedel, Germany) served as radiation source.
      For the visual assessment, the erythema was defined according to COLIPA as the
      first perceptible, clearly defined unambiguous redness of the skin. For the
      colorimetric determination of the erythema, a Chromameter CR 300 (Minolta, Osaka,
      Japan) was used. The threshold for the colorimetry was chosen according to the
      COLIPA recommendation as an increase of the redness parameter delta a* = 2.5. For
      the non-contact perfusion measurements of skin blood flow, a two-dimensional high
      resolution laser Doppler imager (HR-LDI) (Lisca, Linkoping, Sweden) was used. For
      the HR-LDI measurements, an optimal threshold perfusion needed to be established.
      RESULTS: For the HR-LDI measurements basal perfusion +1 standard deviation of all
      basal measurements was found to be a reliable threshold perfusion corresponding
      to the minimal erythema. Smaller thresholds, which would be necessary for
      detection of suberythemal responses, did not provide unambiguous data. All three
      methods, visual scoring, colorimetry and HR-LDI, produced similar SPFs for the
      test products with a variability of < 5% between methods. The HR-LDI method
      showed the lowest variation of the mean SPF. Neither of the instrumental methods,
      however, resulted in an increase of the sensitivity of SPF determination as
      compared with visual scoring. CONCLUSION: Both HR-LDI and colorimetry are
      suitable, reliable and observer-independent methods for MED determination.
      However, they do not provide greater sensitivity and thus do not result in lower
      UV dose requirements for testing.

PMID- 11338404
TI  - Effects on human skin of repetitive ultraviolet-A1 (UVA1) irradiation and visible
      light.
AB  - BACKGROUND: Ultraviolet radiation (UVR) has a variety of effects on human skin.
      Best known are the effects of UVB (290-320 nm) and UVA2 (320-340 nm), which cause
      DNA damage and increased risk of cancer. However, the effects of UVA1 (340-400
      nm) have been not completely investigated. METHODS: The effects of repetitive low
      doses of UVA1 and visible light were studied in 12 healthy individuals. A part of
      the buttock was exposed to 20 J/cm2 UVA1 and another part of 126 J/cm2 of visible
      light three times a week for 4 weeks. Repeated punch biopsies were taken during
      the 4 weeks of treatment and also 2 weeks after the last irradiation. The avidin
      biotin-immunoperoxidase technique was used to investigate the expression of p53,
      p21WAF, bcl-2, Ki67 and cyclin A. RESULTS: By comparison to untreated skin, an
      increased expression of p53 but not p21WAF in keratinocytes was seen. The bcl-2
      protein expression increased slightly after both UVA1 and visible light. An
      increased staining with Ki67 and cyclin A after UVA1 but not after visible light
      was observed as a sign of increased proliferation. CONCLUSION: These results
      suggest that suberythemal doses of UVA1 and even visible light may cause DNA
      damage.

PMID- 11338405
TI  - Effect of ultraviolet A on ornithine decarboxylase and metallothionein gene
      expression in mouse skin.
AB  - BACKGROUND: Ultraviolet A (UVA) is known to induce the expression of many stress
      responsive genes due to the generation of reactive oxygen species (ROS). However,
      UVA's role in inducing metallothionein (MT) gene expression has not been studied.
      Furthermore, our group demonstrated that UVA enhanced 12-O-tetradecanoylphorbol
      13-acetate (TPA)-mediated induction of ornithine decarboxylase (ODC) activity in
      mouse skin (1). METHODS: We examined the interaction of UVA, TPA and antioxidants
      on the induction of MT and ODC mRNA in mouse skin. Female CD-1 mice were exposed
      to UVA (19 J/cm2) and total RNA was isolated from the skin. Northern blot
      analysis for MT and ODC mRNAs was performed. ODC activity in mouse epidermis was
      also determined in some experiments. RESULTS: UVA induced MT mRNA in mouse skin;
      however, it did not increase ODC mRNA. 1,4-Diazabicylo-[2,2,2]-octane (DABCO), a
      singlet oxygen scavenger, reduced UVA-mediated induction of MT mRNA by 40%. The
      data suggest that ROS produced by UVA exposure may contribute to its ability to
      induce MT mRNA. UVA slightly enhanced TPA-mediated ODC mRNA induction, while it
      enhanced ODC enzyme activity 70%. UVA additively intensified TPA-mediated MT mRNA
      induction. alpha-Tocopherol pretreatment inhibited the induction of ODC enzyme
      activity by TPA treatment combined with UVA exposure (TPA + UVA); however, alpha
      tocopherol had less of an inhibitory effect on ODC mRNA induction by TPA + UVA.
      Curcumin, a plant pigment, dramatically inhibited both TPA- and TPA + UVA-induced
      expression of ODC and MT genes. CONCLUSIONS: These results demonstrate that UVA
      can induce MT gene expression and enhance TPA-induced ODC and MT gene expression.
      The data further suggest that these effects are partially mediated by ROS.

PMID- 11338406
TI  - Immunomodulatory effect of extracorporeal photopheresis after successful
      treatment of resistant renal allograft rejection.
AB  - BACKGROUND: Acute renal allograft rejection contributes to patient morbidity.
      Standard immunosuppressives are only partially effective and have significant
      side effects. Extracorporeal photopheresis (ECP) has been effective in reversing
      the acute rejection process. T cell cytokine expression is implicated in
      rejection and tolerance but actual changes in the cytokine profile of ECP-treated
      individuals have not been documented. METHODS: ECP was administered to a patient
      with acute renal allograft rejection resistant to other immunosuppressives.
      Enzyme-linked immunosorbent spot (ELISPOT) assay was performed to determine the
      frequency of mitogen-induced cytokine-producing cells before and after ECP.
      RESULTS: ECP resulted in resolution of rejection; serum creatinine concentration
      fell from 7.1 to 2.2 mg/dl; ELISPOT revealed a three-fold increase in the
      frequency of IL-5 producing cells; IFN-gamma:IL-5 ratio shifted from 2.73 pre
      treatment to 1.01 post-treatment. CONCLUSION: Effective therapy of acute
      allograft rejection with ECP alters the peripheral blood cytokine profile towards
      "type 2" cytokines, suggesting that alteration of T cell cytokine profiles may
      contribute to the resolution of the process.

PMID- 11338407
TI  - Accuracy and reproducibility of simple cross-sectional linear and area
      measurements of brain structures and their comparison with volume measurements.
AB  - Volumetric measurement of brain structure on brain images is regarded as a gold
      standard, yet is very time consuming. We wondered whether simple linear and area
      measurements might be as accurate and reproducible. Two observers independently
      measured the cross-sectional area of the corpus callosum, lentiform and caudate
      nuclei, thalamus, amygdalas, hippocampi, lateral and third ventricles, and the
      width of the sylvian and frontal interhemispheric fissures and brain stem on
      brain MRI of 55 patients using a program written in-house; one observer also
      measured the volumes of the basal ganglia, amygdalo-hippocampal complex and
      ventricular system using Analyze, and performed qualitative assessment of four
      regions (lateral and third ventricles, cortex, and medial temporal lobe) using
      the Lieberman score. All measures were performed blinded to all other
      information. Test objects of known size were also imaged with MRI and measured by
      the two observers using the in-house program. The true sizes of the test objects
      were measured using engineering calipers by two observers blind to the MRI
      results. Differences between the two observers using the same measurement method,
      and one observer using different methods, were calculated. The simple linear and
      cross-sectional area measurements were rapid (20 min versus 5 h for volumetric);
      were highly accurate for test-object measurement versus true size; had excellent
      intraobserver reliability; and, for most brain structures, the simple measures
      correlated highly significantly with volumetric measures. The simple measures
      were in general highly reproducible, the difference (as a percentage of the area
      or width of a region) between the two raters being around 10%, range 0.1%-14.1%,
      (similar to inter-rater variability in previous studies of volume measurements).
      The simple linear and area measures are reproducible and correlate well with the
      measured volumes, and there is a considerable time saving with the former. In
      circumstances where a large volume of work precludes detailed volume measurement,
      simple methods are reliable and can be used instead.

PMID- 11338408
TI  - MRI techniques and cognitive impairment in the early phase of relapsing-remitting
      multiple sclerosis.
AB  - Correlation studies between various conventional and non-conventional MRI
      parameters and cognitive impairment in the early stages of multiple sclerosis
      (MS) are lacking, although it is known that a number of patients with early MS
      have mild cognitive impairment. Our aim was to explore whether this cognitive
      impairment is dependent on the extent and severity of the burden of disease,
      diffuse microscopic brain damage or both. We studied 63 patients with clinically
      definite relapsing-remitting (RR) MS, duration of disease 1-10 years and Expanded
      disability status scale scores < or = 5.0. Mean age was 35.4 years, mean duration
      of disease 5.8 years and median EDSS score 1.5. Neuropsychological performance,
      psychological function, neurological impairment and disability were assessed. The
      patients also underwent MRI, including magnetisation-transfer (MT) studies. We
      quantified the lesion load on T2- and T1-weighted images, the magnetisation
      transfer ratio (MTR) of normal-appearing brain tissue (NABT) and the brain
      parenchymal fraction (BPF). No significant difference was found between lesion
      loads in patients with and without cognitive impairment. In 15 patients (23.8%)
      with overall cognitive impairment, median BPF and average NABT MTR were
      significantly lower than those in patients without cognitive impairment (0.868 vs
      0.892, P = 0.02 and 28.3 vs 29.7 P = 0.046, respectively). Multiple regression
      analysis models demonstrated that the only variables independently correlated
      with cognitive impairment were: BPF (R = 0.89, P = 0.001) and average NABT MTR (R
      = 0.76, P = 0.012). Our findings support the hypothesis that, cognitive decline
      in patients with MS, a low disability score and short duration of disease is
      directly associated with the extent and severity of diffuse brain damage. The
      loss of brain parenchyma did not correlate with the severity of microscopic
      damage in the NABT, indicating that the two processes could be distinct in the
      early stages of the disease.

PMID- 11338409
TI  - Cerebellar blood flow in methylmercury poisoning (Minamata disease).
AB  - We looked at regional cerebellar blood flow in patients with Minamata disease
      (MD) using technetium-99m ethyl cysteinate dimer (99m-Tc-ECD). We carried out
      single-photon emission computed tomography (SPECT) on 15 patients with MD (eight
      men, seven women, aged 51-78 years, mean 70.5 years) and 11 control subjects
      (eight men, three women, aged 62-80 years, mean 72.5 years). Regional blood flow
      was measured in the superior, middle, and inferior portions of the cerebellar
      hemispheres, and the frontal, temporal and occipital cerebral lobes. The degree
      of cerebellar atrophy was assessed on MRI. There were significant differences in
      regional blood flow in all parts of the cerebellum between patients and control,
      but no significant decrease was observed in the cerebrum. Blood flow was lower in
      the inferior cerebellum than in the other parts. Even in patients without
      cerebellar atrophy, flow was significantly decreased regional blood flow in the
      inferior part.

PMID- 11338410
TI  - Diagnosing dural metastases: the value of 1H magnetic resonance spectroscopy.
AB  - The purpose of this study was to assess the value of MRI, MR spectroscopy (MRS)
      and intra-arterial angiography in the preoperative diagnosis of extra-axial dural
      based masses. We prospectively studied 54 patients who underwent preoperative
      MRI, MRS and angiography. Histologically there were 50 meningiomas and four dural
      metastases. MRI and angiography did not allow reliable differentiation between
      meningiomas and metastases. MRS showed elevated choline/creatine ratios in both
      meningiomas and metastases, but there were prominent lipid signals in all
      metastases and a lactate peak in two. This spectroscopic pattern was not found in
      meningiomas. However, following embolisation, they showed similar spectra, due to
      ischaemia and necrosis. We therefore believe MRS to be valuable in differential
      diagnosis of dural metastases and meningiomas prior to embolisation.

PMID- 11338411
TI  - Posterior cerebral artery Wada test: sodium amytal distribution and functional
      deficits.
AB  - Inadequate sodium amytal delivery to the posterior hippocampus during the
      intracarotid Wada test has led to development of selective tests. Our purpose was
      to show the sodium amytal distribution in the posterior cerebral artery (PCA)
      Wada test and to relate it to functional deficits during the test. We
      simultaneously injected 80 mg sodium amytal and 14.8 MBq 99mTc
      hexamethylpropyleneamine oxime (HMPAO) into the P2-segment of the PCA in 14
      patients with temporal lobe epilepsy. To show the skull, we injected 116 MBq
      99mTc-HDP intravenously. Sodium amytal distribution was determined by high
      resolution single-photon emission computed tomography (SPECT). In all patients,
      HMPAO was distributed throughout the parahippocampal gyrus and hippocampus; it
      was also seen in the occipital lobe in all cases and in the thalamus in 11.
      Eleven patients were awake and cooperative; one was slightly uncooperative due to
      speech comprehension difficulties and perseveration. All patients showed
      contralateral hemianopia during the test. Four patients had nominal dysphasia for
      1-3 min. None developed motor deficits or had permanent neurological deficits.
      Neurological deficits due to inactivation of extrahippocampal areas thus do not
      grossly interfere with neuropsychological testing during the test.

PMID- 11338412
TI  - Abducens nerve enhancement demonstrated by multiplanar reconstruction of contrast
      enhanced three-dimensional MRI.
AB  - We describe contrast enhancement of the cisternal portion of the abducens nerve
      and discuss its clinical significance. We examined 67 patients with
      ophthalmoplegia using contrast-enhanced 3-dimensional (3D) MRI with multiplanar
      reconstruction along the nerves and found 16 patients (ten men, six women), aged
      10-73 years (mean 34.4 years), with contrast enhancement of the abducens nerve.
      Of the 36 patients who had an abducens palsy, 14 (39%) showed contrast
      enhancement. In the 16 patients, 23 abducens nerves enhanced; 13 were symptomatic
      and 10 asymptomatic at the time. The causes were disseminated tumour (1), an
      inflammatory process (3), trauma (2), ischaemia (2) and autoimmune diseases (8),
      such as the Miller Fisher syndrome, acute ophthalmoparesis, polyneuropathy and
      multiple sclerosis. Abducens and/or oculomotor nerve enhancement was the only
      abnormality on MRI in the patients with traumatic or ischaemic neuropathy or
      autoimmune diseases. There were 14 patients who recovered fully within 1-6 months
      after treatment, and resolution of the enhancement correlated well with recovery.

PMID- 11338413
TI  - The role of hypertension in bromocriptine-related puerperal intracranial
      hemorrhage.
AB  - The spate of medicolegal inquiries following the disqualification of Parlodel
      (bromocriptine mesylate) by the Food and Drug Administration for postpartum
      ablactation, uncovered previously unreported side effects associated with its
      postpartum administration. In 1994, bromocriptine mesylate was withdrawn from the
      market as a milk suppressant. Since this time, over a dozen cases of postpartum
      intracranial hemorrhages associated with its use have been reported. We describe
      three additional cases of postpartum intracranial hemorrhage related to
      bromocriptine usage. One patient, previously normotensive, developed hypertension
      and a headache; initial CT was normal, but CT 24 h later demonstrated
      intracranial hemorrhage. This suggests that the blood-pressure elevation was drug
      induced and was the cause, rather than the consequence, of bromocriptine-related
      intracranial hemorrhage.

PMID- 11338414
TI  - Magnetisation transfer imaging of the normal adenohypophysis: the effect of sex
      and age.
AB  - Magnetisation transfer (MT) techniques provide tissue contrast depending mainly
      on the concentration of macromolecules. Because many macromolecules are involved
      in the secretory activity of the pituitary gland, MT techniques might be useful
      in the study of pituitary gland disorders. Our purpose was to establish a
      quantitative database of the MT ratio (MTR) of the normal adenohypophysis and to
      see whether there are age- and sex-related differences. Using a three-dimensional
      gradient-echo sequence for MT we studied the adenohypophysis in 56 males and 61
      females aged 7 months-77 years; postsaturation images were obtained using an on
      resonance binomial prepulse. The images were normal in all but three patients,
      two with meningiomas, one with a schwannoma). Adenohypophyseal MTR increased in
      both sexes up to 19 years of age (r = 0.47 males, 0.39 females, P < 0.05). In men
      after 20 years and in women from 20-49 years MTR decreased (r = -0.68, P < 0.001,
      r = -0.46, P < 0.05, respectively). In women aged 50-59 years the MTR again
      increased slightly. The MTR in males was slightly higher at all ages except
      before 9 and after 50 years of age. These differences were not statistically
      significant except in the 40-49 year group (P < 0.05).

PMID- 11338416
TI  - Suprasellar cavernous malformation presenting with extensive subarachnoid
      hemorrhage.
AB  - Cavernous malformations are usually intraparenchymal, extra-axial lesions being
      uncommon. They have very rarely been reported as the cause of subarachnoid
      hemorrhage. We present a case of hemorrhage related to a cavernous malformation,
      unusual in two ways. First, it is rare for an intracranial cavernous malformation
      to present with massive subarachnoid hemorrhage. Secondly, this cavernous
      malformation lay in the chiasmatic cistern.

PMID- 11338415
TI  - Granular-cell tumour: a rare suprasellar mass.
AB  - Granular-cell tumour is a rare suprasellar space occupying lesion, which usually
      presents with visual deterioration, endocrine deficits or headache. We present
      two women with extraordinarily large tumours, measuring 3.8 and 4.0 cm in
      diameter. In both cases the tough, vascular tumour could be removed only
      subtotally.

PMID- 11338417
TI  - Cavernous haemangioma in the cavernous sinus: case report and review of the
      literature.
AB  - We report a cavernous haemangioma in the left cavernous sinus. This lesions very
      rarely occurs in this site and is difficult to diagnose correctly preoperatively.
      CT, angiography and MRI permit differentiation of the cavernous haemangioma from
      other tumours in this region and thereby contribute to a better surgical
      approach. The radiological features of cavernous haemangioma reported in the
      literature are summarised.

PMID- 11338418
TI  - Lacunar infarct during pallidotomy: case report.
AB  - A symptomatic lacunar infarct is an unusual complication which may develop during
      stereotactically guided pallidotomy using radiofrequency thermoablation. We
      describe a 54-year-old man with Parkinson's disease involving predominantly the
      right side, progressively deteriorating under medical management. He underwent
      stereotactically guided radiofrequency thermoablation of the posteroventral
      globus pallidus interna. Despite intraoperative microelectrode recording and
      stimulation, the patient developed right facial weakness and pronator drift
      during the procedure. MRI showed a small lacunar infarct in the left internal
      capsule, in addition to the appropriately placed ablative lesion. We discuss the
      potential mechanisms for this type of injury.

PMID- 11338419
TI  - Syringomyelia associated with adhesive spinal arachnoiditis: MRI.
AB  - We reviewed the MRI of seven patients with syringomyelia associated with
      surgically proven adhesive spinal arachnoiditis to describe clinical and MRI
      findings in this condition. Using 0.5, 1.0 or 1.5 tesla units, we obtained
      sagittal T1- and T2-weighted spin-echo and axial T1-weighted images. Additional
      sagittal T2-weighted images were obtained without using motion-artefact
      suppression. Contrast medium was given intravenously to five patients. The syrinx
      cavities were thoracic in five cases, cervicothoracic in one, and extended from
      C4 to L1 in one. No Chiari malformation or craniovertebral junction anomaly was
      demonstrated. Meningeal thickening was seen on T2-weighted sagittal images only
      in one case. Cord deformity due to adhesion or displacement due to an associated
      arachnoid cyst was seen in all cases best demonstrated on axial images. Focal
      blurring of the syrinx wall on axial images was seen in six patients. Flow voids
      were seen in the syrinx fluid in all cases on T2-weighted images obtained without
      motion-artefact suppression. No abnormal contrast enhancement was demonstrated.

PMID- 11338420
TI  - The "botryoid sign": a characteristic feature of rhabdomyosarcomas in the head
      and neck.
AB  - We investigated nine patients with rhabdomyosarcoma in the head and neck (6-53
      years of age), using CT and MRI. The tumours originated in the paranasal sinuses
      (3), cheek (2), soft palate (1), orbit (1), sternocostoclavicular muscle (1) and
      parapharyngeal space (1). The histological subtype was embryonal in five,
      alveolar in three and pleomorphic in one case. The tumours enhanced markedly and
      heterogeneous on CT and MRI. The masses were isointense or gave slightly higher
      signal than surrounding muscles on T1- and heterogeneously high signal on T2
      weighted images. In four tumours, multiple ring enhancement resembling bunches of
      grapes. This appears to be characteristic of rhabdomyosarcoma and probably
      reflects a component of botryoid-type rhabdomyosarcoma in which mucoid-rich
      stroma is covered with a thin layer of tumour cells. We have named this imaging
      feature the "botryoid sign".

PMID- 11338421
TI  - Bilateral vertebral artery balloon occlusion for giant vertebrobasilar aneurysms.
AB  - We describe the clinical presentation, radiological and clinical results in six
      consecutive patients with a giant vertebrobasilar aneurysm treated by bilateral
      vertebral artery balloon occlusion. Five patients presented with headache and
      signs of brain-stem compression and one with subarachnoid haemorrhage. In all
      patients vertebral artery balloon occlusion was performed. In four, this followed
      successful test occlusion. In one patient, who did not tolerate the test
      occlusion, a bypass from the external carotid to the posterior cerebral artery
      preceded definitive vertebral artery occlusion. One patient underwent bypass
      surgery prior to test occlusion. At 6-22 months follow-up three patients had a
      good functional outcome and showed unchanged size or shrinkage of the aneurysm on
      MRI. Three other patients died; one from recurrent haemorrhage, and two probably
      from delayed brain-stem ischaemia. The presence of two large posterior
      communicating arteries predicted good functional outcome, which was also related
      to the clinical condition at presentation, and the degree of brain-stem
      compression and oedema on MRI. Bilateral vertebral artery balloon occlusion can
      be considered in patients with otherwise untreatable giant vertebrobasilar
      aneurysms. If test occlusion is not tolerated, a surgical bypass to the posterior
      circulation can be considered.

PMID- 11338422
TI  - Prevalence and inheritance of hip osteoarthritis in Iceland.
AB  - The purpose of this study was to: (I) assess the prevalence of hip osteoarthritis
      (OA) in Iceland and compare it with that in Southern Scandinavia, (II) determine
      the incidence of total hip replacement (THR) for primary OA in Iceland, (III)
      compare two different methods for defining radiographic hip OA, (IV) assess in a
      population-wide study in Iceland the genetic contribution t hip OA leading to
      THR, and (V) perform a genome-wide scan of a large Icelandic family to identify a
      chromosomal susceptibility locus for hip OA leading to THR. many Icelandic
      patients with hip OA have been well aware that this disease "goes in the family".
      by examining a large proportion of all Icelandic colon radiographs taken 1990
      1996 the prevalence of radiographic hip OA in Iceland was found to be at least
      five-fold higher compared to Swedish and Danish studies that have used the same
      methods. A comparison of two methods for estimating hip OA from colon radiographs
      showed that a simple quantitative method of measuring joint space was more
      reliable than a qualitative method. The age-standardized incidence of THR for
      primary hip OA in Iceland between 1982 and 1996 was estimated and found to be
      about 50 percent higher than for Sweden. The higher Icelandic prevalence of hip
      OA may explain most of this difference. To investigate the contribution of
      heritability to hip OA leading to THR, information from two population-wide
      database in Iceland was combined: A national registry of THR between 1972 and
      1996, and a genealogy database of all Icelandic genealogy records for the last 11
      centuries made available by deCode Genetics. The genetic contribution to THR for
      OA was assessed by (a) identifying familial clusters of THR for OA, (b) applying
      the minimum founder test (MFT) to estimate the minimum number of ancestors to
      account for all patients with THR for OA, compared to the average number of
      founders for control lists, (c) calculating an average pairwise kinship
      coefficient (KC) for the patient and control lists, (d) estimating the relative
      risk (RR) for relatives of patients with THR for OA. A large number of familial
      clusters of patients with THR for OA were identified. MFT showed that OA patients
      descended from fewer founders than the control groups. The average pairwise KC
      among patients with OA was greater than in the population. RR for siblings of THR
      for OA patients was 3.05 (2.52, 3.10). Icelandic patients with THR for OA are
      thus significantly more related to each other than are matched controls. These
      findings support a significant genetic contribution to a common form of OA and
      encourages the search for genes conferring an increased susceptibility to OA. New
      techniques now make it possible to search the whole human genome for chromosomal
      susceptibility loci associating with OA. A genome wide scan was done to identify
      susceptibility loci for hip OA leading to THR, using DNA from a large Icelandic
      family with a very high prevalence of primary hip OA. A genome locus with a lod
      score of 2.58 was identified on chromosome 16p. A similar locus has been reported
      on from England. This is the first instance where what may be the same
      susceptibility locus for OA is independently described in two different
      populations with hip OA. We have identified other families with hip OA which link
      to the studied family and are continuing an expanded genome-wide scan. Continued
      studies of the kind outlined here will clarify the complex genetic background of
      OA and identify genetic variation associated with the disease. In addition to
      improving our understanding of the pathogenesis of OA and identifying new
      molecular targets for treatment, this will allow a better insight into the
      interactions between genetic background and environmental factors that initiate
      and drive OA.

PMID- 11338423
TI  - Genetic load and coadaptation of chromosomal inversions. II. O-chromosomes in
      Drosophila subobscura populations.
AB  - We have analysed the inversion polymorphism and genetic load of O-chromosomes in
      three populations of D. subobscura from southeastern Europe. As expected for a
      central populations the inversion polymorphism was extensive. In a like fashion,
      the genetic load, in particular the frequency of lethals, was heavy in all three
      populations. There were significant differences in the frequency of moderately
      deleterious genes. These differences in viability can be attributed to balancing
      selection. A comparison of these two kinds of genetic polymorphism indicates that
      there are differences in mean viability among different gene arrangements of O
      chromosomes in the three populations. The differences observed are due to an
      unequal distribution of various viability classes among O-chromosome gene
      arrangements. We here show for the first time a specific distribution of lethal
      genes among these arrangements within the Palearctic distribution area of D.
      subobscura. The lethal allelism test showed lethals are non-randomly associated
      with the Ost gene arrangement. The amount of genetic load is heavy in gene
      arrangements with a high frequency, in comparison with the ones with a low
      frequency. Lethal genes may be protected in combinations of low and moderate
      frequency gene arrangements that harbor more lethal genes, as the Ost in the one
      population. Some arrangements that are less protected against recombination have
      a higher load than ones that are more protected against recombination. This can
      be taken as evidence for coadaptation.

PMID- 11338424
TI  - Genetic diversity and fitness in peripheral and central populations of the
      European tree frog Hyla arborea.
AB  - Genetic diversity is expected to decrease in small and isolated populations as a
      consequence of founder effects, bottlenecks, inbreeding and genetic drift. In
      this study we analyse temporal and spatial effects on genetic variation and
      progeny viability of the European tree frog (Hyla arborea) at two scales. First,
      the Swedish distribution has been isolated from the continental distribution for
      more than 8000 thousand years, and secondly, within Sweden, recent habitat
      alterations that have taken place during this century have increased isolation
      between local populations. Genetic variation and progeny survival in relation to
      isolation was studied within the entire Swedish distribution of the tree frog.
      Allozyme electrophoresis analysis of froglets, sampled across the Swedish
      distribution, revealed a low overall genetic variation (1.06 alleles/locus) at
      the protein level in comparison with continental populations (1.54-1.68
      alleles/locus). However, egg hatchability (97%) and early larval survival (95%)
      were not lower than in other parts of the tree frog distribution or in other
      anuran species. Within the Swedish distribution, early larval survival was lower
      in isolated breeding ponds than in more central ones. However, no differences in
      genetic variation were found in relation to isolation. Polymorphism was detected
      only at a single locus, and was restricted geographically to the eastern part of
      the Swedish distribution. Bottlenecks due to climatic changes and fragmentation
      of suitable habitat (primarily natural pastures with ponds) are suggested as
      possible causes of the low genetic diversity of the Swedish tree frog population.

PMID- 11338425
TI  - Patterns and levels of genetic differentiation in North American populations of
      the Alaskan wheatgrass complex.
AB  - Levels and distribution of genetic variation were assessed using six allozymes in
      27 populations of Alaskan wheatgrass (Elymus alaskanus) from different locations
      in Canada, USA, Greenland and Russia to obtain information on the genetic
      structure of these populations. The enzyme systems were ACO, DIA, GPI, MDH, PGM
      and SKD. Allozyme variation at the species level was high, with 64.3% (Ps) of the
      loci being polymorphic, an average number of alleles per locus of 1.9 (As), and
      an average genetic diversity of 0.17 (Hes). Differentiation was found in the
      populations studied, with the following findings: (1) statistically significant
      differences were found in allele frequencies among populations for every
      polymorphic locus (P < 0.001); (2) 63% of the total allozyme variation at
      polymorphic loci was partitioned among populations (GST = 0.63); (3) relatively
      low mean genetic distances between the populations were obtained (mean D =
      0.029); (4) the genetic structure of Russian populations are clearly distinct
      from the other populations, the cluster and principal component analyses revealed
      the same genetic patterns of relationships among populations. This study also
      indicates that E. alaskanus contains different levels of allozyme variation in
      its populations. Furthermore, some banding patterns at the loci Aco-1, Aco-2, Gpi
      2, Mdh-1, Skd-1, Skd-2 can be used as markers to identify individual populations.

PMID- 11338426
TI  - Allozyme variation in 16 natural populations of Faidherbia albida (Del.) A. Chev.
AB  - The objectives of this study were (1) to investigate the genetic variability; and
      (2) to determine the phylogenetic relationship in the leguminous tree Faidherbia
      albida through out its range of distribution in East, West and Southern Africa. A
      total of 16 populations were subjected to enzyme electrophoresis and 6 enzyme
      systems (Adh, Mdh, G6pdh, Idh, 6Pgdh, and alpha-Est) encoded by 12 loci were
      scored. A total of fifty one different alleles were detected, with an average of
      2.5 alleles per locus. Forty three percent of the loci were polymorphic at a 95%
      criterion. The average expected heterozygosity (gene diversity index H(e)) was
      0.141. All provenances showed significant deviation from Hardy-Weinberg
      expectation. The UPGMA cluster analysis, based on Modified Rogers distance
      revealed close similarities between Eastern and Southern African provenances,
      except Debre zeit from Ethiopia, which was closest to West African populations
      than to the East African populations. Also, Bignona from West Africa was
      peculiarly closer to East African provenances. Differentiation of West African
      populations from Eastern and Southern African provenances was quite evident,
      emphasising the clinical pattern of variation in these two major geographical
      races of F. albida in Africa. Wright's F-statistics showed an overall significant
      deficit of heterozygotes, a common feature in mixed mating, entomophilous,
      widespread species such as F. albida. The dendrogram analysis showed wide
      separation among the three Ethiopian provenances indicating a high level of
      genetic differentiation and diversity among them.

PMID- 11338427
TI  - Cytogenetic analysis of Epicauta atomaria (Meloidae) and Palembus dermestoides
      (Tenebrionidae) with Xyp sex determination system using standard staining, C
      bands, NOR and synaptonemal complex microspreading techniques.
AB  - The mitotic and meiotic chromosomes of the beetles Epicauta atomaria (Meloidae)
      and Palembus dermestoides (Tenebrionidae) were analysed using standard staining,
      C-banding and silver impregnation techniques. We determine the diploid and
      haploid chromosome numbers, the sex determination system and describe the
      chromosomal morphology, the C-banding pattern and the chromosome(s) bearing NORs
      (nucleolar organizer regions). Both species shown 2n = 20 chromosomes, the
      chromosomal meioformula 9 + Xyp, and regular chromosome segregation during
      anaphases I and II. The chromosomes of E. atomaria are basically metacentric or
      submetacentric and P. dermestoides chromosomes are submetacentric or
      subtelocentric. In both beetles the constitutive heterochromatin is located in
      the pericentromeric region in all autosomes and in the Xp chromosome; additional
      C-bands were observed in telomeric region of the short arm in some autosomes in
      P. dermestoides. The yp chromosome did not show typical C-bands in these species.
      As for the synaptonemal complex, the nucleolar material is associated to the 7th
      bivalent in E. atomaria and 3rd and 7th bivalents in P. dermestoides. Strong
      silver impregnated material was observed in association with Xyp in light and
      electron microscopy preparations in these species and this material was
      interpreted to be related to nucleolar material.

PMID- 11338428
TI  - Cytogenetic proof that the brine shrimp Artemia franciscana (Crustacea,
      Branchiopoda) is found in Argentina.
AB  - Artemia brine shrimps are commercially important and they have been extensively
      studied. This branchiopod crustacean is extensively used in aquaculture and other
      commercial and applied practices. The genus also awakes an increasing interest
      worldwide as an experimental model in other basic areas of research such as
      evolution and cytogenetics. In the present work adult male meiosis and nauplii
      mitotic cells in two Artemia populations from Argentina (Mar Chiquita and Las
      Tunas, Cordoba Province) are analyzed and compared to the reference strains A.
      franciscana (Great Salt Lake, Utah, USA) and A. persimilis (Salinas Grandes de
      Hidalgo, La Pampa Province, Argentina). The Mar Chiquita population shows the
      diploid and haploid numbers characteristic of A. franciscana, and a regular male
      meiosis. In the Las Tunas population diverse diploid and haploid numbers are
      encountered, and an irregular meiosis is observed in some individuals.
      Fluorescent DAPI and CMA banding shows bright chromocenters of intermediate size
      and number in both populations. Cytogenetic and phenotypic data show that the
      population of Mar Chiquita could be assigned to A. franciscana; the variation
      found in chromocenter size and number reflects an heterochromatin polytypism
      already observed in this species. The cytogenetic and morphological traits in Las
      Tunas population suggest an occasional hybridization between A. franciscana and
      A. persimilis.

PMID- 11338429
TI  - Partial albinism in a semi-isolated population of great reed warblers.
AB  - Albinism in birds is thought to result from the expression of recessive alleles
      that disrupt melanin pigmentation at feather development. We have studied great
      reed warblers Acrocephalus arundinaceus in a recently founded and increasing
      population in Sweden during 15 years for the presence of birds with albinistic
      feathers. The study population was founded in 1978 and the few cases of albinism
      was exclusively recorded during the first five years of our study (1985-1989).
      This fits to the expected pattern if albinism is governed by recessive alleles;
      we have previously demonstrated that the population suffered from inbreeding
      during the first years of our study. The albinistic birds experienced a similar
      lifetime reproductive success as normally coloured birds.

PMID- 11338430
TI  - Enhancement of micronuclei frequency in the Tradescantia/micronuclei test using a
      long recovery time.
AB  - The Tradescantia/micronuclei test (TRAD/MCN) is a well-validated test for
      monitoring environmental genotoxicants. These pollutants induce at the early
      meiotic stage of pollen mother cells chromosome fragments which become
      micronuclei at the tetrad stage. The standard test protocol requires some hours
      of exposure of the inflorescences and a recovery time of about 24 hours to reach
      the early tetrad stage. Since the recovery period represents a critical step of
      the TRAD/MCN, experiments were performed to establish its length in plants of
      clone #4430 of the hybrid T. hirsutiflora x T. subacaulis which is widely used in
      environmental monitoring. The aim of the present research was to ascertain the
      exact duration of recovery time in order to improve the sensitivity of the
      TRAD/MCN test. First, studies were performed to select the flowers at the
      beginning of the meiosis, and then anthers were sampled and studied for a period
      of 48-86 hours. The complete meiosis in the plants examined required about 80
      hours. Second, exposure to genotoxic substances followed by different recovery
      times was carried out to demonstrate that effectiveness of the TRAD/MCN test is
      closely related to the duration of the recovery time. The test was carried out by
      exposing inflorescences to known mutagens (sodium azide and maleic hydrazide) for
      six hours followed by different recovery times (24-72 hours). The results showed
      that the frequency of micronuclei in the pollen mother cells increased with the
      length of the recovery time.

PMID- 11338431
TI  - House mice with metacentric chromosomes in the Middle East.

PMID- 11338432
TI  - Polymorphic microsatellite markers within the MHC of Peromyscus polionotus.

PMID- 11338433
TI  - Population genetics of Chrysomela tremulae: a first step towards management of
      transgenic Bacillus thuringiensis poplars Populus tremula x .P. tremuloides.
AB  - Many strategies have been proposed for delaying the development of insect
      resistance to Bacillus thuringiensis (Bt). The current paradigm for Bt resistance
      management is the high dose-refuge strategy. For this strategy to be successful:
      (i) heterozygotes must be killed in treated areas, (ii) resistant alleles must be
      rare (frequency < 10-3), and (iii) there must be a high level of gene flow
      between populations to ensure random mating. We studied gene flow within and
      between populations with a view to managing the resistance of Chrysomela tremulae
      (Coleoptera: Chrysomelidae) to new transgenic, highly toxic poplars expressing a
      synthetic Bt gene. In this study, we assessed the extent of gene flow in C.
      tremulae within and between 16 sites in France and Belgium, using allozyme
      markers. We found a high level of genetic variability in C. tremulae, with a mean
      of 0.206 +/- 0.16. There were no obvious limitations to gene flow between
      populations of C. tremulae over large geographical distances (several hundreds of
      kilometres). Nevertheless, a very low level of genetic differentiation was
      observed between a site located in the south of France and the sampled sites from
      the Centre region.

PMID- 11338434
TI  - Cytogenetic analysis shows that the unusually large chromosome in the sex-limited
      pB silkworm (Bombyx mori) strain consists of three chromosomes.
AB  - We have discovered an inordinately large chromosome pair at the pachytene stage
      in the oocyte of the sex-limited pB (black larval marking) silkworm (Bombyx mori)
      strain (TWPB). We have analyzed the composition and arrangement of this large
      chromosome. A genetic linkage analysis shows that the large chromosome is made up
      of the W chromosome, the second chromosome fragment (pB fragment), and the fifth
      chromosome (linkage group) containing at least the region from map position 0.0
      to 40.8. We also observed a sex heterochromatin body (SB) that we deduced to be
      made up of condensed W chromosomes. The number of SBs in each female nucleus
      among the sucking stomach cells of the TWPB strain was variable. Evidently, the W
      chromosome of the TWPB strain is attached to another chromosome. The composition
      of the W chromosome, the second chromosome fragment, and the fifth chromosome was
      studied through linkage analysis for these three chromosomes. We used two strains
      derived from the TWPB strain, the sex-limited pM (moricaud larval marking)-like
      (TWPML) and the autosomal pM-like (T5PML). The results show that the TWPML strain
      originates through a detachment of the fifth chromosome from the large chromosome
      of the TWPB strain, and the T5PML strain originates through a detachment of the W
      chromosome from that. Accordingly, the large chromosome of the TWPB strain is
      arranged in the order W chromosome--second chromosome fragment--fifth chromosome.

PMID- 11338435
TI  - Sensitivity and specificity of new serum markers for mild cardionecrosis.

PMID- 11338436
TI  - Quality in cancer care.

PMID- 11338437
TI  - The relationship between spirituality and Eysenck's personality dimensions: a
      replication among English adults.

PMID- 11338438
TI  - Values and antisocial behavior among Spanish adolescents.
AB  - A number of studies have indicated that delinquent adolescents have
      characteristic value systems. However, most of these studies have adopted a
      "known-groups" design--that is, they have compared institutionalized delinquents
      and non-institutionalized adolescents, assuming those adolescents to be non
      delinquent. Designs of this type do not distinguish effectively between the
      statistical effects of delinquency and of institutionalization. In this study,
      the authors investigated relationships between values and self-reported
      antisocial behavior in three adolescent groups: 435 school-attending boys, 529
      school-attending girls, and 95 delinquent boys in juvenile rehabilitation centers
      or prisons. The results indicate that antisocial behavior is associated with
      hedonistic values and a lack of interest in conventional values and social
      values. These relationships cannot be explained by the institutionalization
      effects.

PMID- 11338439
TI  - Children's theories of god: explanations for difficult-to-explain phenomena.
AB  - Participants in 3 age groups (preschoolers, 3rd graders, and college students)
      generated explanations for various phenomena. Participants with higher levels of
      religious involvement provided more attributions to God than participants with
      lower levels of religious involvement. Also, older participants provided more
      attributions to God than younger participants. The results suggest that
      individuals who have higher levels of religious involvement develop theorylike
      understanding based on their conception of God. It appears that this theorylike
      understanding has explanatory utility that increases with age.

PMID- 11338440
TI  - Self-reported anxiety in children and adolescents: a three-year follow-up study.
AB  - Anxiety may be more transient in children and adolescents than in adults. The
      present study involves a longitudinal design enabling the investigation of the
      continuity/discontinuity of self-reported anxiety in children and adolescents. A
      sample of 68 children was followed over 3 years. Results indicate that, on the
      whole, self-reported anxiety decreased over time. This was true for overall
      anxiety and its sub-types, with the exception of social concerns/concentration,
      which did not decrease over time. Consistent with past research involving normal
      fear, girls and younger children were found to score higher on anxiety than boys
      and older children did. However, those groups scoring higher at inception also
      demonstrated the most marked decreases over the 3-year period. In addition to the
      changes found over time, the data indicated continuity in anxiety such that
      levels of anxiety at inception were significant predictors of follow-up anxiety,
      although only a small amount of variance was shared. The authors concluded that
      adult models of anxiety cannot be applied to youth and that future research
      should investigate the contribution of contextual factors to the development of
      anxiety in children.

PMID- 11338441
TI  - Paternal and maternal influences on family functioning among Hong Kong Chinese
      families.
AB  - The linkages between dyadic relationships in the family and family functioning
      were examined in 378 Chinese families on two occasions. The following dyadic
      relationships were investigated: (a) parent-child relationship qualities reported
      by adolescent children (questionnaire and interview measures of parenting style,
      parent-adolescent conflict, parent-adolescent communication, and parent
      adolescent relationship) and by their parents (questionnaire measures of parent
      child relationship quality and demand); and (b) marital quality reported by the
      parents via questionnaire measures. Results showed that parents' and children's
      views of family functioning were longitudinally related to dyadic relationships
      in the family. Relative to mother-adolescent relationship and mothers' report of
      marital quality, father-adolescent relationship and fathers' report of marital
      quality were generally found to have a stronger association with perception of
      family functioning and its change over time.

PMID- 11338442
TI  - Relational scaffolding of school motivation: developmental continuities in
      students' and parents' ratings of the importance of school goals.
AB  - The authors investigated whether parents and students are consistent, over grade
      levels, in the importance they assign to school goals. Elementary and high school
      students (n = 178) and their parents (n = 130) completed a questionnaire
      addressing the personal importance of students' school goals, defined in terms of
      school success. Parent-child consistencies in the rating patterns of school goals
      over grade levels were more common than were inconsistencies. These developmental
      consistencies support the position that students' school goals are embedded
      within the parent-child relationship (J. Youniss, 1980; J. Youniss & J. Smollar,
      1985) and are scaffolded within it (J. S. Bruner, 1975; L. S. Vygotsky, 1978).
      Potential sources of relational and phenotypic influences on school goals are
      discussed, as is the need for effective friendship management and school
      performance in high school.

PMID- 11338443
TI  - Gender differences in adolescent self-esteem: an exploration of domains.
AB  - The relationship between gender and global self-esteem in adolescence, while
      modest, has been well established, with boys consistently scoring higher than
      girls. In the present study, we sought to understand gender differences in
      adolescent self-esteem in terms of its component parts. With a relatively large
      (n = 545) sample of adolescents, drawn from Grades 8, 10, and 12, we specified 8
      domains of adolescent self-esteem (personal security, home/parents, peer
      popularity, academic competence, attractiveness, personal mastery, psychological
      permeability, and athletic competence) across a number of different instruments
      and brought them together into a common assessment superstructure. Gender
      differences as well as the relative contributions of the different domains to
      overall self-esteem scores were measured. As predicted, boys attained slightly
      higher global self-esteem scores than girls did, by a difference of .22 standard
      deviation units. Contrary to our expectation of more balanced domain effects,
      boys significantly outperformed girls in 6 of 8 domains, whereas the 2 remaining
      domains exhibited no significant gender differences. There were no main or
      interaction effects for grade level. In terms of relative contribution of these
      domains to global self-esteem for the 2 genders, global self-esteem in boys and
      girls is predicted in very similar strengths and in the same order of magnitude
      by identical domains of self-esteem: home/parents, personal security, academic
      competence, attractiveness, and personal mastery--yielding multiple R2s from .88
      to .91.

PMID- 11338444
TI  - Recognizing limitations.

PMID- 11338445
TI  - Part of the process.

PMID- 11338446
TI  - Improving visually guided action and perception through use of prisms.
AB  - BACKGROUND: Severe loss of vision can occur as a result of insults to the visual
      system. Depending on the level of insult, the patient can experience symptoms
      ranging from simple loss of visual acuity to more-complex visual motor and
      perceptual disorders, like visual-field loss and accompanying spatial
      disorientation, all of which can result in significant restrictions to the
      patient's mobility. This report describes the therapeutic use of ophthalmic
      prisms to treat patients with distinct visual impairments. CASE REPORTS: The
      management of four patients, each with visual impairment of unrelated origins
      (age-related macular degeneration, brain injury, Friedreich's ataxia, stroke) are
      discussed, with special emphasis on the positive impact of prismatic
      prescriptions. With each case, we also discuss our reasoning for prescribing the
      particular prisms and their possible roles. CONCLUSIONS: Our clinical reports
      reinforce the notion that prisms can be effectively used in visual
      rehabilitation. The modulatory role of prisms is considered in terms of the
      neurology of the brain and its functions.

PMID- 11338447
TI  - Idiopathic juxtafoveal retinal telangiectasis: case report and literature review.
AB  - BACKGROUND: Idiopathic juxtafoveal retinal telangiectasis (IJRT) is an uncommon
      cause of vision loss. It is characterized by irregularly dilated capillaries in
      the macula, often found temporal to the fovea and straddling the horizontal
      raphe. These telangiectatic vessels appear similar to microaneurysms and can be
      difficult to detect without fluorescein angiography. Varying degrees of vessel
      leakage and exudation are also common features. Three distinct types of IJRT have
      been described on the basis of clinical features. Within the spectrum of disease
      encompassed by IJRT, it can affect either gender--present unilaterally or
      bilaterally--and occur at any age. CASE REPORT AND REVIEW: Presented here is a
      case with type 1A idiopathic juxtafoveal retinal telangiectasis and a review of
      all types.

PMID- 11338448
TI  - Dorsal midbrain syndrome secondary to a pineocytoma.
AB  - BACKGROUND: Dorsal midbrain syndrome is a triad of signs consisting of vertical
      gaze palsy, light-near dissociation of the pupils, and convergence retraction
      nystagmus. Associated findings may also be present. The most-common etiologies
      are pineal gland tumors and midbrain infarction. Pineal gland tumors are rare
      tumors that show a predilection for males. The specific tumor reported herein, a
      pineocytoma, shows no gender predilection and is most common in mid- to late
      adulthood. CASE REPORT: A 38-year-old Native American man came to us with signs
      and symptoms consistent with dorsal midbrain syndrome. A neurological evaluation
      revealed the presence of a pineocytoma, which was later excised unsuccessfully.
      An explanation of the findings associated with dorsal midbrain syndrome is
      provided. CONCLUSION: Patients who demonstrate signs consistent with dorsal
      midbrain syndrome should be referred for a neurological evaluation--including an
      MRI--to rule out any midbrain lesion.

PMID- 11338449
TI  - Verifying and evaluating progressive addition lenses in clinical practice.
AB  - BACKGROUND: Despite the fact that more than 50% of multifocal lenses dispensed in
      the United States are progressive addition lenses, adequate methods for clinical
      verification of these lenses have been lacking. Using automated lens meter
      techniques, the author describes a simplified method for verification of these
      complex lenses. METHODS: Thirty pairs of progressive lenses were measured in a
      modified method using a Humphrey 330 Lens Analyzer. Fifteen pairs were "premium
      quality" progressive lenses: fifteen pairs were "non-premium-quality"
      progressives. Five criteria were assessed on each lens: Distance Zone Width
      (DZW). Intermediate Zone Width (IZW), Near Zone Width (NZW), Drop Distance (DD),
      and Maximum Astigmatic Distortion (MAD). RESULTS: "Premium-quality" progressive
      lenses failed to demonstrate clear-cut superiority over "non-premium-quality"
      progressive lenses in the five specified criteria. Individual measurements
      indicate considerable product inconsistency affected every brand tested.
      CONCLUSIONS: Premium- and non-premium-quality progressive lenses demonstrated
      similar performance characteristics in this study. Zone size variation in these
      lenses was found to be considerable, a characteristic that seemed to cut across
      brand lines. The AO Compact lens seemed to demonstrate a shorter drop distance
      than other lenses, which does enhance its suitability for use with small frames.
      A comparison of the Essilor Natural PAL to the Younger Image lens showed little
      difference in the categories measured, although peripheral distortions seemed
      closer to the reading zone in the image. A comparison of the MAD of lenses in
      this study to lenses tested in 1986 indicates a considerable improvement has been
      made in that important characteristic.

PMID- 11338450
TI  - Prevalence and laterality of lattice retinal degeneration within a primary eye
      care population.
AB  - PURPOSE: The purpose of this study was to determine the prevalence of lattice
      retinal degeneration (LRD) in a primary eye care population and to compare this
      prevalence to that of other studies reported from selected populations. In
      addition, the percentage of unilateral and bilateral cases was to be determined.
      METHODS: A prospective study design was conceived to examine 600 consecutive
      patients presenting to the UABSO Primary Care Clinics. Each patient had been
      appointed for general eye examination. The following data were collected
      contemporaneously over six months from September 1993 to March 1994:
      demographics, medical and ocular history; refractive correction (calculated and
      recorded as spherical equivalent, SE); best-corrected visual acuity; and the
      presence and features of all ocular fundus findings, as evaluated through a
      dilated pupil. RESULTS: Of the 600 patients examined, 31 (5.2%) had LRD. Subjects
      ranged in age from 14 to 78 years (mean, 37.4 +/- 17.9 yrs.). Seventeen (55%) of
      the patients were white and 14 (45%) were black; 21 patients (68%) were female
      and 14 (32%) were male. The mean refractive correction (SE) was -1.77 D (range,
      +2.25 to -8.00 D). The lesions were bilateral in 19 (61.3%) of the patients;
      unilateral in 12 (38.7%). LRD lesions were observed in the vertical meridian
      (within 30 degrees of 6 or 12 o'clock) in all patients. CONCLUSIONS: The
      prevalence of LRD in a primary eye care population is comparable to that reported
      from other, selected populations. The proportion of bilateral cases in our
      material was greater than that from some other studies. Another item of note from
      the present data was exclusively vertical geographic location. We attribute the
      greater prevalence of bilateral cases in this material to the nature of the eye
      care delivery system.

PMID- 11338451
TI  - Testing the inhibitory effects of Mascara Life on bacterial growth in mascara.
AB  - BACKGROUND: Mascara Life is a liquid additive that claims to reconstitute mascara
      consistency while retarding bacterial and fungal growth in tubes of used mascara.
      The purpose of this study was to compare the effectiveness of mascara alone
      versus mascara with the addition of Mascara Life against the growth of
      Staphylococcus aureus, a common bacterial contaminant responsible for potentially
      serious ocular infections. METHOD: To simulate 3 to 6 months of use, 12 new tubes
      of Maybelline Great Lash mascara were dried for 5 consecutive days with the
      applicator wands removed. Mascara Life was added to a set of six tubes and an
      equal amount of saline was added to another set of six tubes. Equal amounts of
      eugonic broth were added to each tube to provide nutrients for the organisms and
      to further dilute the mascara. One tube from each set served as a negative
      control. The ten remaining tubes were inoculated with a standardized suspension
      of Staphylococcus aureus. Two calibrated samples from each tube were plated onto
      blood agar at 0, 1, 7, 14, 21, and 28 days after initial inoculation. The number
      of viable organisms was determined after 24 hours of incubation by the plate
      count method. RESULTS: The concentration of viable bacteria was reduced to zero
      by day 7, and remained at this level through day 28 in all inoculated tubes. The
      negative control tubes showed no growth throughout the study. CONCLUSION: The
      preservatives in both mascara and mascara with the addition of Mascara Life are
      effective in retarding growth of Staphylococcus aureus.

PMID- 11338452
TI  - The effect of coatings on impact resistance.

PMID- 11338453
TI  - You can succeed in low vision.

PMID- 11338454
TI  - Building long-term patient relationships.

PMID- 11338455
TI  - [New markers for the risk of sudden death: analysis of ventricular
      repolarization].
AB  - The identification of patients at high risk of sudden cardiac death is one of the
      greatest challenges for cardiologists. Non-invasive methods have,
      characteristically, low predictive sensitivities and specificities. The role of
      abnormalities of ventricular repolarisation (QT interval) in the genesis of
      ventricular arrhythmias has been well established by experimental data. For this
      reason, parameters of ventricular repolarisation on the surface electrocardiogram
      have been proposed. However, taken in isolation, these markers are limited in
      terms of arrhythmic risk stratification. This report analyses the value of the
      different parameters of ventricular repolarisation in the identification of high
      risk: QT dispersion, QT dynamics and T wave alternans. The dispersion of the QT
      interval is a marker of unhomogenous ventricular depolarisation. This concept
      must be applied differently in such pathologically dissimilar diseases such as
      myocardial infarction, cardiomyopathy or the long QT syndrome. Moreover,
      methodological problems make the interpretation of many experimental studies very
      delicate. Frequency dependence of the QT helps select high risk patients after
      myocardial infarction or with dilated cardiomyopathy. A common feature of
      pathological ventricular myocardium is the more pronounced frequency-dependency
      of the QT interval. The predictive value of this new index should be evaluated
      and compared with other non-invasive risk factors in prospective trials. Studies
      of T wave alternans in selected high risk populations, essentially patients with
      coronary artery disease and dilated cardiomyopathy, have shown this parameter to
      be predictive of arrhythmia. The predictive value requires confirmation in much
      larger populations at lower levels of risk of arrhythmia and sudden death in
      prospective trials. A new field of research has opened up in the study of
      ventricular repolarisation. Many studies have been undertaken on the duration of
      the QT interval, the morphology of the QT (including T wave alternans and post
      pause changes) and, finally, the dynamics of the QT interval. By regrouping,
      analysing and using these data correctly, we should be able to identify new
      markers of high arrhythmic risk.

PMID- 11338456
TI  - [Holter monitoring in 2000].
AB  - Ambulatory 24 hour monitoring was developed in the United States and bears the
      name of its inventor, Holter. It was introduced in France for the first time by
      the Lariboisiere school, 25 years ago, and the end of the year 2000 is an
      appropriate time to review this tool. What are the new clinical indications,
      technical progress and prospects for the future? All the efforts of both
      cardiologists and engineers for the past 25 years have been focused on gathering
      information about the system of cardiac regulation which is more or less
      concealed in the ECG recordings. As far as arrhythmias are concerned, or the QRS
      or T wave morphology, or the circadian variations of sinus rate and
      depolarisation, the studies are numerous but not always easily applicable in
      clinical practice. However, the non-invasive analysis given by the Holter
      recording guarantees a promising future in terms of new discoveries and
      applications.

PMID- 11338457
TI  - [Treatment of refractory cardiac failure by resynchronization].
AB  - Permanent resynchronisation as a complementary treatment of refractory cardiac
      failure has recently been reported. There have been several publications
      demonstrating the value of this new therapeutic approach, based on improved
      quality of life and exercise capacity. The benefits depend on careful patient
      selection, accurate positioning of the pacing catheters, especially the left
      ventricular catheter, and on individual follow-up. The present data completely
      justifies the pursuit of research projects in this new therapeutic domain by
      using on-going studies to define its impact on mortality.

PMID- 11338458
TI  - [Arrhythmic cardiomyopathy].
AB  - Arrhythmic cardiomyopathy (ACM) is a clinical entity which can be reproduced in
      experimental models and which corresponds to all myocardial changes induced by
      chronic tachycardia. It may affect the atria and/or ventricles and, in this case,
      occur with all types of arrhythmia. Arrhythmia complicating a cardiomyopathy is
      the differential diagnosis of ventricular ACM. Nevertheless, the potential
      deleterious haemodynamic changes of any chronic arrhythmia may aggravate pre
      existing ventricular dysfunction and, therefore, should always be considered. The
      development of ACM is usually progressive and depends on the heart rate, but
      there may also be a myocardial predisposition in certain cases. ACM is an
      association of haemodynamic, electrophysiological, metabolic and histological
      changes. Regression, which is the rule, starts in the first days following
      control of the ventricular rhythm but continues clinically over several months.
      The physiopathological mechanisms of ACM are multiple and include essentially
      abnormal cellular calcium concentrations. The treatment is optimally the
      restoration and maintenance of sinus rhythm, or at least control of the
      ventricular rate. Because of its curative effects, selective radiofrequency
      ablation of the arrhythmogenic substrate is the treatment of choice when this is
      localised. In chronic atrial fibrillation, when sinus rhythm cannot be
      maintained, the control of the ventricular response at rest and on exercise
      depends on pharmacological treatment, and, when ineffective, on radiofrequency
      modification of atrioventricular conduction with optimisation of the pacing mode.

PMID- 11338459
TI  - [Electrocardiographic alternans].
AB  - A simple ECG curiosity or a precursor of serious arrhythmia, associated with
      pericardial effusion or a sign of inotropic alteration, the phenomenon of
      electrical alternans has intrigued clinicians and research workers in its
      multiple facets, mechanical and electrical, consequences on PR interval, QRS
      complex or ventricular repolarisation. As a consequence, the causal mechanisms
      are very different, but these last few years, a predominant role of calcium flux,
      especially intracellular, has been demonstrated. Recently, clinical interest in
      this phenomenon has been revived with the demonstration of micro-alternans of
      repolarisation, apparently a new marker for the risk of sudden death.

PMID- 11338460
TI  - [Atypical flutters].
AB  - Typical atrial flutter may now be definitely treated in a single session.
      However, the very meaning of the term, atrial flutter, is confusing because it is
      a multiple entity. In fact, flutters may be classified with respect to their
      electrocardiographic and electrophysiological features. In addition to typical
      common atrial flutter with biphasic, predominantly negative F waves in the
      inferior leads and positive F waves in V1 due to an anticlockwise macro-reentry
      circuit localised to the right atrium, there are other forms which may be
      described as typical in that they pass through the cavo-tricuspid isthmus. They
      include typical flutter with inverted rotation, short loop inferior flutter and
      flutter with a double reentry circuit. In 2001, it would seem licit to call all
      flutters which do not pass through the cavotricuspid isthmus atypical,
      independently of their surface ECG appearances. The term flutter still refers to
      a continuous electrical activity with absence of an isoelectric line in at least
      one lead but with extremely variable ECG features. They may be classified as
      flutter on pre-existing lesions, with right or left atrial macro-reentry
      circuits. The ECG appearance is then that of very atypical flutter. More
      recently, flutters with circuits passing through the coronary sinus have been
      described. Ablation of the muscle of the coronary sinus seems to be able to treat
      this type of flutter, the prevalence of which is not yet known.

PMID- 11338461
TI  - [Refresher course in rhythmology].

PMID- 11338462
TI  - [Bouveret's tachycardia].
AB  - In 1889, in an age preceding the invention of the electrocardiogram, a physician
      working in the hospitals of Lyon published a remarkable paper on essential
      paroxysmal tachycardia, of which Bristowe in England and Huppert in Germany had
      already spoken. The study described 12 cases (including 3 personal cases) of
      essential paroxysmal tachycardia and 6 secondary tachycardias. They were not all
      benign, there being 4 deaths out of the 12 cases. From this period on, the term
      "Bouveret's tachycardia" has been used in France and, with the advances in
      rhythmology, some have assimilated it to paroxysmal nodal tachycardia. In fact,
      many forms of paroxysmal essential tachycardia have been recognised at atrial
      (nodal tachycardia, accessory pathway tachycardia, idiopathic atrial flutter and
      fibrillation) and ventricular levels (benign or ventricular Bouveret's
      tachycardia). This is an occasion to review the variety of clinical medicine in
      the accuracy of a rhythmological diagnosis without forgetting that the
      electrocardiogram is essential when the recordings are analysable. The term of
      Bouveret's tachycardia should be retained but, before electrocardiographic
      analysis, it englobes all paroxysmal tachycardia occurring in healthy hearts, and
      not only paroxysmal nodal tachycardia.

PMID- 11338463
TI  - Graves' thyroid ophthalmopathy in Ethiopian patients.
AB  - In a prospective study, we evaluated the clinical manifestations, severity,
      complication and management of Graves' thyroid ophthalmopathy (GTO) in 37
      Ethiopian patients. Twenty-seven were females and 10 were males (F:M = 2.7:1).
      The mean age was 35 years (range 19-70 yrs). The mean duration of ocular symptoms
      was 33.4 months (range 2-120 months) while the mean duration of hyperthyroid
      symptoms was 36.2 months (range 6-120 months). GTO was found in 30 (81.1%)
      hyperthyroid, 1 (2.7%) hypothyroid and 5 (13.5%) euthyroid patients. Upper lid
      retraction was the most common clinical finding, being detected in 31 (83.8%) of
      the patients. One (2.7%) patient had marked extraocular muscle involvement,
      involving the inferior rectus muscle of one eye. Though 18 (48.6) patients had
      signs of soft tissue inflammation, only 4 (10.8%) required the administration of
      systemic steroids to control the inflammatory process. None of our patients had
      sight loss from the complications of GTO. Larger prospective studies are
      suggested to evaluate both the prevalence and possible racial difference in its
      clinical presentation.

PMID- 11338464
TI  - Screening for enteropathogenic Escherichia coli (EPEC) in paediatric patients
      with diarrhoea and controls using pooled antisera.
AB  - A total of 421 strains Escherichia coli isolated between 1992 and 1993 from
      paediatric patients with diarrhoea (n = 345) and controls (n = 76) less than 2
      years of age at Ethio-Swedish Children's Hospital, Addis Ababa, Ethiopia were
      screened for enteropathogenic E. coli (EPEC) on the basis of slide agglutination
      tests using E. coli polyvalent and pooled antisera I, II and III. The individual
      pools of antisera comprised the following serotypes: Pool I (O26:B6, O55:B5,
      O111:B4, O127:B8), Pool II (O86:B7, 0119:B14, 0125:B15, 0126:B16, 0128:B12) and
      Pool III (025:11L, Oll:74L, 078, 0114, 0124). Of the 345 E. coli isolates from
      patients 72 (20.8%) and of the 76 E. coli isolates from controls 13 (7.1%) were
      positive for EPEC. Of the 345 E. coli strains, 21 (6.1%) and of the 76 E. coli
      strains, 5 (6.6%) were positive for more than one pool of antisera. This study
      shows that the most common serotypes among EPEC from Ethiopia correspond to the
      most frequent serotypes from other parts of the world. A limited number of pooled
      antisera were sufficient to screen the majority of the EPEC isolates.

PMID- 11338465
TI  - Childhood meningitis in a tertiary hospital in Addis Ababa: clinical and
      epidemiological features.
AB  - Hospital based prospective study of 136 children aged 3 months to 12 years
      admitted as cases of meningitis between June 1996 and May 1997 was undertaken to
      assess the epidemiological features, evaluate the outcome and measure the
      duration of clinical improvement after initiation of treatment. Infants accounted
      for 79 (58%) of cases and 23 (68%) of deaths. Next to fever and vomiting,
      neurologic signs were the commonest presentation. H. influenzae, S. pneumoniae
      and N. meningitidis accounted for 90% of culture isolates. Delayed presentation,
      partial treatment, altered sensorium at admission and pneumococcal meningitis
      were risk factors for mortality. The morbidity and mortality rates were 25% of
      total cases each. The mean duration of fever was 3.7 (+/- 2.27) days after
      treatment. The morbidity and mortality rates are still high in this hospital.

PMID- 11338466
TI  - Radioiodine treatment of hyperthyroidism at the Tikur Anbessa Hospital.
AB  - Thirty-four hyperthyroid patients selected on preset criteria for radioiodine
      therapy were given low dose radioiodine-131 (I-131) in the Nuclear Medicine Unit
      of the Tikur Anbessa Hospital as a preferential alternative to repeat or
      protracted administration of antithyroid drugs, or surgery. The dose chosen was
      85 uCi per gram of thyroid tissue based on the 24 hour uptake of a test dose of I
      131. The age range of the patients was 18 to 68 years, female to male ratio was
      7.5:1 and 80% of the females were in the reproductive age group. Twenty-five
      patients had multinodular goiter, four had persistent hyperthyroidism after
      surgery, and five had recurrent Graves' disease. Estimated thyroid gland weight
      was from 3.5 to 51.4 grams and the amount of I-131 administered was from 0.2 to
      4.9 mCi. Only 11 of the 34 patents became euthyroid after a single dose of I-131,
      14 required one or more repeat doses and only six of those became euthyroid
      making a total of 17 (50%) responders. The low dose regimen we used in this
      study, though economical in a situation of limited I-131 supply, resulted in a
      high failure rate of 50%. This shows the need to formulate a better dosage scheme
      that can benefit the majority of patients by optimizing the prospects of the
      resolution of hyperthyroidism with a single dose of radioiodine.

PMID- 11338467
TI  - Embryonal rhabdomyosarcoma of the orbit in a 38-year-old woman.
AB  - Primary embryonal rhabdomyosarcoma of the orbit is an extremely rare tumor in
      adults. A 38 year old female patient with immunohistochemically proved embryonal
      rhabdomyosarcoma of the right orbit is reported. The histologic types, diagnosis,
      management and out come of rhabdomyosarcoma is discussed.

PMID- 11338468
TI  - Solitary plasmacytoma of the mesentery with nodular amyloid deposits: a case
      report with immunohistochemical evaluation.
AB  - The mesentery is unusual site for plasmacytoma. We have observed a solitary
      primary mesenteric plasmacytoma with marked nodular deposits of Congophilic
      amyloid in a 38 year-old man. We believe the present case represents the first
      case of primary extraosseous mesenteric plasmacytoma in the English literature.
      The clinical picture, pathologic findings and immuno-histochemical studies are
      discussed. Autopsy and long-term follow up are needed to determine whether this
      patient is at risk of developing multiple myeloma, local recurrence, metastatic
      foci or probable complications related to amyloidosis.

PMID- 11338469
TI  - Reproductive health: conceptual and operationalization challenges.
AB  - This review article is a teaching material for those who are engaged in
      reproductive health (RH) service delivery, managers, policy makers, professionals
      and the RH community. It also aims at addressing the RH concept and indicates
      some of the operationalization modalities, challenges and attempts to promote the
      realization of RH and population programmes in the country. It has been shown
      time and again that even five years after the International Conference on
      Population and Development (ICPD), policy makers, administrators and service
      providers still lack an understanding of not only the integrated approach of RH
      services, but the concept of RH also. In addition, the majority poorly perceives
      the RH rights notion. It is imperative that issues like understanding of the
      integrated approach of RH services, ensuring the adequacy of the information or
      choices offered to women and emphasis on the quality of care offered to clients
      have to be addressed urgently and adequately. The conceptualization and
      operationalization of RH will require full understanding of the health,
      population and women policies, legal and institutional implications of these
      concepts and the actions needed to convert them into reality. In order to achieve
      better results, commitment not only of relevant governmental agencies but also by
      non-governmental organizations (NGOs) and the RH community is a prerequisite.
      This includes allocation of adequate resources and proper interpretation of the
      RH concept in the Ethiopian context.

PMID- 11338470
TI  - 25th Kellersberger memorial lecture, 2000. The contribution of immunology to
      tuberculosis control.

PMID- 11338471
TI  - Demographic impact of HIV/AIDS in Addis Ababa.
AB  - Using secondary data from various sources, a model was adopted as installed in
      Demproj. software program to determine the demographic impact of HIV/AIDS
      epidemic in Addis Ababa. It was found that the adult HIV prevalence will reach a
      plateau level of about 10.8% in the year 2001 and 10.3% in the year 2004
      respectively. AIDS will slow the decline in infant mortality rate and under 5
      mortality rates and will increase crude death rate and lower the life expectancy
      at birth by about 15 years by 2004 compared to the "no AIDS" scenario. AIDS will
      reduce the size of the Addis Ababa population by about 160,000 people by the year
      2004, but will not stop or make its growth negative. Based on the above findings
      preventive measures such as STD control, condom promotion, IEC and blood
      screening, and approaching the problem multisectorally, incorporating the
      HIV/AIDS epidemic in the demographic projection and establishing HIV/AIDS data
      base were recommended.

PMID- 11338472
TI  - Laboratory medicine in the 21st Century.

PMID- 11338473
TI  - Correlation of morphologic and cytogenetic parameters of genetic instability with
      chromosomal alterations in in situ carcinomas of the breast.
AB  - Classification of preinvasive breast disease could be better founded using
      biologic markers, thereby increasing reproducibility. We studied 57 breast ductal
      and lobular in situ carcinomas by means of comparative genomic hybridization and
      correlated these findings with quantitative features such as the mean nuclear
      area, mitotic index (MI), apoptotic index (AI), and the presence or absence of
      necrosis. Loss of 8p and gains of 8q and 6q were associated, respectively, with a
      significantly higher MI and AI, whereas loss of 16q was associated with a lower
      MI and AI. A significantly higher number of alterations per case were seen in
      tumors with gains of 6q, 8q, and 17q and tumors with loss of 13q. Loss of 16q and
      gain of 17q correlated with the absence or presence of necrosis, respectively.
      Our data clearly demonstrate that distinct cytogenetic changes correlate with
      phenotypic changes, proliferation, and apoptosis. These data may be used to
      refine existing classification schemes.

PMID- 11338474
TI  - Ubiquitin as a marker of cell injury in nonalcoholic steatohepatitis.
AB  - Ubiquitin (UB), an intracellular protein that binds to other proteins to target
      them for proteolysis, is associated with Mallory hyalin (MH), which supports a
      biopsy diagnosis of nonalcoholic steatohepatitis (NASH). We analyzed 54 liver
      biopsy specimens from 49 patients with a clinical diagnosis of NASH for
      immunoreactive UB and multiple features of necroinflammation, fibrosis, and
      Prussian blue-positive iron to determine whether the presence of immunoreactive
      UB increases detection of MH or correlates with other features of cell injury or
      mutations of the HFE gene. MH and UB were graded. Analysis for HFE gene mutations
      was performed in 48 patients. Biopsy diagnoses were distributed as follows: NASH,
      42; steatosis, 10; and nonspecific changes, 2. UB was present in 20 specimens and
      MH in 23. Of 31 specimens with 0 MH, 6 had UB; of 14 with 1 + (questionable) MH,
      7 had 1+ or 2+ UB. UB correlated positively and significantly with the diagnosis
      and grade of NASH, presence of MH, cell swelling, lobular inflammation, and
      fibrosis. Immunostaining for UB may enhance detection of MH in questionable
      cases, support the diagnosis of NASH, and indicate which patients may be at risk
      for progression of disease.

PMID- 11338475
TI  - Cytogenetic aberrations in primary and recurrent fibrolamellar hepatocellular
      carcinoma detected by comparative genomic hybridization.
AB  - Fibrolamellar hepatocellular carcinoma (FLC) is a rare entity of hepatocellular
      carcinoma (HCC) not yet analyzed cytogenetically. By using comparative genomic
      hybridization (CGH), we looked for chromosome changes in 2 primary FLCs and a
      recurrent FLC with and without metastases. CGH revealed an amplification of 1q in
      1 primary FLC. The other primary FLC and a metastasis revealed no changes. The
      recurrent FLC showed 18 aberrations, including 1q+, 2p+, 3p+, 3q+, 4p+, 4q+, 5p+,
      5q+, 6q+, 8p+, 8q+, 9q+, 12p+, 12q+, 18p+, 18q+, Xp+, and Xq+. In 2 metastases, 9
      and 10 aberrations were seen, including 1q+, 3p-, 3q-, 4q+, 5p+, 5q+, 8q+, 10p+,
      10q+, Xp+, and Xq+. In 9 cases of other entities of HCC, a mean of 10.2
      aberrations per case were detectable affecting 1q (7 cases), 4q (5), 5q (4), 6q
      (5), 8p (5), 8q (5), 9p (4), 9q (5), 16q (4), 17p (5), and 17q (4). Chromosomes
      2p, 2q, 3p, 3q, 4p, 5p, 6p, 7p, 7q, 10q, 11p, 11q, 12p, 12q, 13q, 14q, 16p, 18p,
      18q, 20p, 20q, and 21q were altered in up to 3 samples. Our findings indicate
      striking differences in the number of chromosomal imbalances in primary FLC and
      recurrent FLC, whereas imbalances seen in the recurrent FLC and the other
      entities of HCC were similar in number and chromosomes involved. It may be
      speculated that these aberrations represent secondary events based on a genetic
      instability and do not mirror the primary alterations in these carcinomas.

PMID- 11338476
TI  - A model for pretest probability of lymph node metastasis from cutaneous Melanoma.
AB  - Although many statistical models have been developed to predict survival in
      cutaneous melanoma, few predict the end point of regional lymph node metastasis
      shortly after the diagnosis of melanoma. We used routine clinical and histologic
      data from 573 patients referred to the Duke University Melanoma Clinic, Durham,
      NC, during the 1980s and 1990s who underwent lymph node resections during the
      first year after the diagnosis of primary cutaneous melanoma. The outcome we
      modeled (using the logistic regression model) was the probability of lymph node
      metastasis. We found that tumor thickness was the variable most significantly
      associated with the probability of nodal metastasis, and the presence of
      ulceration and tumor location also were significant, but age, sex, and mitotic
      rate were not. When the resulting logistic model predicted that the probability
      of nodal metastasis was more than .6, 93 of 115 patients had nodal metastasis.
      When the model predicted that the probability was less than .3, just 32 of 88
      patients had positive nodes. Furthermore, after the result of the node sampling
      was known, Cox model analysis demonstrated that the pretest probability added
      significant information about subsequent survival.

PMID- 11338477
TI  - Quantitative analysis of valvular lesions during Bartonella endocarditis.
AB  - Cardiac valve pathology was evaluated in 15 patients with confirmed diagnosis of
      Bartonella endocarditis. Ten were infected by Bartonella quintana and 5 by
      Bartonella henselae. Histologic features of these cases, including fibrosis,
      calcification, vegetation, pattern of inflammation, and vascularization, were
      compared with those of valves from 25 cases of non-Bartonella endocarditis as
      controls using a computerized quantitative image analysis. Pathologic and
      immunohistologic testing for localization of Bartonella species in resected
      valves included Warthin-Starry stain and polyclonal antibody-based
      immunodetection. Compared with other cases of infective endocarditis, cases of
      Bartonella endocarditis are more fibrotic and calcified, less vascularized, with
      less extensive vegetation and chronic inflammation. These pathologic changes are
      suggestive of a prolonged infection. Warthin-Starry stain and immunohistologic
      testing demonstrated the presence of the organism, respectively, in 11 and 10 of
      the 13 tested valves. Results of both staining methods showed microorganisms in
      extracellular locations and in regions unaccompanied by inflammation. Pathology
      and immunohistology may contribute to the etiologic diagnosis of Bartonella
      endocarditis when serology and molecular techniques are not available.

PMID- 11338478
TI  - Allelic loss involving the tumor suppressor genes APC and MCC and expression of
      the APC protein in the development of dysplasia and carcinoma in Barrett
      esophagus.
AB  - Samples of Barrett metaplastic specialized epithelium (SE), low-grade dysplasia
      (LGD), high-grade dysplasia (HGD), and invasive adenocarcinoma (CA) derived from
      36 esophagectomy specimens were studied for loss of heterozygosity (LOH) in APC
      and MCC and for expression of APC protein. Of 18 cases that were heterozygous
      (informative) for APC, LOH was found in none of 14 SE samples, 2 of 8 LGD
      samples, 3 of 11 HGD samples, and 5 of 17 CA samples. Immunohistochemically,
      markedly reduced expression of APC protein (< 50% positive cells) was found in 3
      of 19 HGD samples and 4 of 35 CA samples but not in SE or LGD samples. Of 17
      cases informative for the MCC gene, LOH was detectable in 1 of 14 SE samples,
      none of 7 LGD samples, none of 9 HGD samples, and 4 of 16 CA samples. Allelic
      loss of APC and/or loss of APC protein expression occurs earlier in the
      metaplasia-dysplasia-carcinoma sequence in Barrett esophagus than LOH in the MCC
      gene. The determination of alterations at APC or MCC would be of limited
      importance for the surveillance of patients with Barrett esophagus.

PMID- 11338479
TI  - Minimal adenocarcinoma in prostate needle biopsy tissue.
AB  - One of the major diagnostic challenges in prostate needle biopsy interpretation
      is definitive establishment of a malignant diagnosis based on a minimal or
      limited amount of carcinoma in needle biopsy tissue. Major and minor diagnostic
      criteria should be used for interpretation of small foci of carcinoma. The
      constellation of findings and a combination of the major and minor diagnostic
      criteria permit a definitive diagnosis of focal adenocarcinoma. The differential
      diagnosis of minimal prostatic adenocarcinoma in needle biopsy tissue is broad
      and includes many benign lesions. The benign entities most likelty to be
      misdiagnosed as minimal prostatic adenocarcinoma are atypical adenomatous
      hyperplasia (adenosis) and atrophy. High-grade prostatic intraepithelial
      neoplasia and a descriptive diagnosis of focal glandular atypia or atypical small
      acinar proliferation also should be considered before diagnosing minimal
      adenocarcinoma. The most valuable adjunctive study for the diagnosis of minimal
      adenocarcinoma is immunohistochemistry using antibody 34 beta E12, reactive
      against basal cell-specific high-molecular-weight cytokeratins. Most cases can be
      diagnosed based on H&E-stained sections without this immunostain. Most minimal
      carcinomas in prostate needle biopsy tissue are of intermediate histologic grade,
      and most are indicative of pathologically significant carcinoma in the whole
      prostate gland.

PMID- 11338480
TI  - CD5+ follicle center lymphoma. Immunophenotyping detects a unique subset of
      "floral" follicular lymphoma.
AB  - The "floral" variant of follicle center lymphoma (FCL) may be confused with
      progressive transformation of germinal centers or lymphocyte predominance Hodgkin
      lymphoma. Immunohistochemistry and gene rearrangement studies are usually
      sufficient to differentiate among these entities. We present 11 cases of floral
      FCL that were evaluated at our institution by flow cytometry,
      immunohistochemistry, or both and by polymerase chain reaction-based molecular
      analysis. In 4 cases, the neoplastic B cells coexpressed CD5 antigens; 3 of these
      4 cases also were CD10+, and all demonstrated rearrangement within the bcl-2
      locus. These findings demonstrate that a subset of floral FCL is CD5+.
      Recognition of this immunophenotype is important to avoid misdiagnosis of nodular
      variants of small lymphocytic lymphoma and mantle cell lymphoma. Studies suggest
      that expression of CD5 by neoplastic germinal center cells might result from
      alterations of the follicular microenvironment and/or inappropriate B-cell
      responses to cytokine networks.

PMID- 11338481
TI  - Measurement of total RBC volume relative to lean body mass for diagnosis of
      polycythemia.
AB  - An elevated total RBC volume (TRCV) in milliliters per kilogram of body weight
      has been an essential criterion for determining whether a person is polycythemic.
      This may be misleading in obese subjects as the TRCV per kilogram of fat is only
      one-tenth that of the TRCV of the lean body mass (LBM). Various formulas based on
      surface area have been used to account for this difference, but they are not
      always reliable. Direct measurement of TRCV per kilogram of lean body mass was
      obtained originally in studies in which body composition was determined by the
      combined body density and total body water measurement method. This is
      impractical as a routine procedure, but simple-to-use instruments are now
      available for direct measurement of a person's body composition and percentage of
      fat by impedance technology. Thus, the TRCV can be obtained by a direct
      measurement that discounts the effects of fat, and a graph has been designed to
      normalize the TRCV to milliliters per kilogram of LBM. The TRCV for men and women
      has been established as 36 mL/kg LBM; when it is more than 43 mL/kg LBM, a
      diagnosis of polychthemia can be made with confidence.

PMID- 11338482
TI  - A reliable screening test to identify adult carriers of the (--SEA) alpha zero
      thalassemia deletion. Detection of embryonic zeta-globin chains by enzyme-linked
      immunosorbent assay.
AB  - Homozygous (--SEA) alpha zero-thalassemia deletion, the cause of up to 80% of
      fetal hydrops in Southeast Asia, is encountered in many other countries.
      Heterozygous carrier rates of the deletion in Southeast Asian populations range
      from 4% to 14%. The laboratory screening for adult carriers of (--SEA) and other
      alpha zero-thalassemia deletions currently rests primarily with microscopic
      detection of hemoglobin H inclusion bodies within erythrocytes (Hb H screen).
      This test is laborious and observer dependent and has poor sensitivity. We
      assessed a colorimetric enzyme-linked immunosorbent assay (ELISA) to detect
      embryonic zeta-globin chains in adult hemolysates as an alternative to detect (-
      SEA) alpha zero-thalassemia deletion carriers. Blood samples from 221 adults with
      a mean corpuscular volume less than 80 micron 3 (80 fL) were studied
      prospectively by currently accepted hemoglobin screening tests and ELISA.
      Suspected cases of alpha-thalassemia were confirmed by DNA-based diagnostics.
      ELISA was highly sensitive (1.0) and specific (0.94) for the detection of adult
      carriers of (--SEA) alpha zero-thalassemia deletion. The hemoglobin H screen had
      a sensitivity of 0.47 and specificity of 0.99. The zeta-globin ELISA proved
      simple to perform, rapid, and applicable to high volume or population-based
      screening programs.

PMID- 11338483
TI  - Mortality risks, costs, and decision making in transfusion medicine.
AB  - Traditional quality-adjusted life year (QALY) cost analysis is complex and
      assigns arbitrary dollar values to catastrophic outcomes such as death. Analysis
      of transfusion medicine technologies by an alternative approach that focuses on
      costs to avoid fatal outcomes might be a useful adjunct to QALY analysis for
      allocating limited financial resources. We estimated the cost per death averted
      for the following interventions: apheresis platelets vs random platelets, solvent
      detergent-treated plasma vs untreated plasma, and leukocyte-reduced vs unmodified
      transfusions in cardiac surgery. As a control, similar data were calculated for
      current donor viral testing. The estimated incremental costs per death avoided
      were as follows: single-donor apheresis platelets, $15 million; solvent detergent
      plasma, $17 million; leukocyte-reduced transfusions in cardiac surgery, $11,000;
      HIV-1 antibody testing, $22,000; and HIV-1 antigen testing, $3.9 million. The
      estimated number of deaths averted per year in our hospital were as follows:
      apheresis platelets, 0.1; solvent detergent plasma, 0.044; leukocyte-reduced
      transfusions, 14; HIV-1 antibody testing, 6.0; and HIV-1 antigen testing, 0.033.
      HIV-1 antibody testing and leukocyte-reduced transfusions in cardiac surgery are
      comparably cost-efficient means of averting mortality in patients receiving
      transfusions. Solvent detergent plasma and apheresis platelets are comparatively
      expensive approaches to reducing mortality from transfusion complications.

PMID- 11338485
TI  - Cytologic detection of Toxoplasma gondii tachyzoites in cerebrospinal fluid.
AB  - We reviewed our case records to see how often Toxoplasma gondii organisms were
      identified by cytologic evaluation of cerebrospinal fluid (CSF). During a 12-year
      period, 6,090 CSF specimens were examined, and 2 cases (0.03%) showed
      tachyzoites. Both patients were immunocompromised. One patient underwent lumbar
      and ventricular taps, and the other underwent only ventricular tap. Organisms
      were identified in the ventricular specimens but not in the lumbar sample. Both
      patients were treated, and subsequent ventricular CSF samples were negative.
      Toxoplasma gondii can be identified by cytologic examination of CSF. Our results
      confirm prior observations that in patients with obstructive hydrocephalus,
      tachyzoites are more likely to be found in ventricular rather than lumbar
      specimens.

PMID- 11338486
TI  - Precursor B-lymphoblastic transformation of grade I follicle center lymphoma
      following rituximab therapy.

PMID- 11338484
TI  - Sensitive differential detection of genetically related mycobacterial pathogens
      in archival material.
AB  - A polymerase chain reaction (PCR) assay targeted to the immunogenic protein MPB64
      gene was used to detect members of the Mycobacterium tuberculosis complex, and an
      outward-primed PCR (OPPCR) designed on the IS6110 element allowed differentiation
      between Mycobacterium bovis and Mycobacterium tuberculosis. Additionally, the
      amplification of IS1110 and 16S ribosomal RNA sequences combined with a dot
      blotting assay were able to differentially detect Mycobacterium avium,
      Mycobacterium intracellulare, and Mycobacterium paratuberculosis. The validity of
      the experimental procedure was tested on reference material and formalin-fixed
      paraffin-embedded samples from patients with tuberculosis, sarcoidosis, or Crohn
      disease. We demonstrated mycobacterial DNA in 59 of 75 cases with histologic
      lesions typical of tuberculosis; we detected M tuberculosis and M
      paratuberculosis in 6 of 25 sarcoidosis cases and in 7 of 20 Crohn disease
      specimens, respectively. The proposed diagnostic procedure is directly applicable
      to archival material and allows differentiation of genetically related
      mycobacterial pathogens in more detail than other molecular methods. It provides
      a tool for the diagnostic study of tuberculosis, sarcoidosis, and Crohn disease.

PMID- 11338487
TI  - Coexpression of c-Myc and p53 as a marker of survival time.

PMID- 11338488
TI  - The article abstracted by Dr. Patricia N.R. Pereira in the "Critical Appraisal"
      section of the Journal of Esthetic Dentistry.

PMID- 11338489
TI  - Dentin bonding, caries control.

PMID- 11338490
TI  - The science of communicating the art of esthetic dentistry. Part II: Diagnostic
      provisional restorations.
AB  - Provisional restorations fulfill many functions in restorative dentistry. Quality
      provisional restorations can provide the clinician, the patient, and the
      laboratory technician much valuable information prior to fabrication of the
      definitive restoration. Such diagnostic provisional restorations fabricated with
      acrylic resin are easily adjusted and modified until both esthetic and functional
      results are approved by the patient. Once this approval has been obtained, the
      definitive restorations can be fabricated with confidence, using the esthetic
      form of the provisional restorations as a blueprint.

PMID- 11338491
TI  - Bioactive glass granules for regeneration of human periodontal defects.
AB  - PURPOSE: A comparative study which evaluated the effectiveness of bioactive glass
      granules of uniform size (300-335 microns) for the regenerative treatment of
      interproximal intrabony periodontal defects was conducted. MATERIALS AND METHODS:
      Twelve pairs of advanced periodontal lesions in 12 patients (6 males and 6
      females) were treated in a split-mouth design with open flap debridement in the
      control sites and open flap debridement with bioactive glass particles placed in
      the test sites. RESULTS: At 6 months post-treatment, both treatment modalities
      demonstrated a gain in clinical attachment level (CAL), with the test sites
      having a significantly (p < .01) greater gain in CAL than the control sites.
      Reentry procedures were performed to assess the amount of hard tissue fill. The
      test sites demonstrated significantly (p < .001) more gain in hard tissue fill
      than the controls.

PMID- 11338492
TI  - Color stability of compomer after immersion in various media.
AB  - PURPOSE: The purpose of this study was to evaluate the effect of various media on
      the color stability of compomer and to compare these results to those of other
      materials that could be used in similar clinical circumstances. MATERIALS AND
      METHODS: In this test, six materials (shade A2) were used: four compomers
      (Dyract, Compoglass F, Xeno, F2000), one composite resin (Clearfil AP-X), and one
      resin-modified glass ionomer cement (Fuji II LC). There were four test solutions:
      one alcoholic (whiskey), two low pH soft drinks (Coca Cola, orange juice), and
      deionized water as a control. A plastic ring mold (9-mm diameter x 1-mm height)
      was used to prepare 120 disk specimens. For 60 days, the test specimens were
      immersed in the various media daily for 3 hours then transferred to the deionized
      water. Color was measured by CIE L* a* b* relative to CIE source against a white
      background, using a colorimeter. Color change (delta E*) was calculated as delta
      E* = [(delta L*)2 + (delta a*)2 + (delta b*)2]1/2. Color changes (delta E*) were
      recorded after 1, 7, 30, and 60 days. RESULTS: The results indicated that
      compomer and resin-modified glass ionomer were susceptible to discoloration in
      various solutions over an extended period of time. Composite resin showed minimal
      perceptible color change. Specimens immersed in whiskey showed a significantly
      high perceptible color change (p < .0001). Water caused no perceptible color
      changes.

PMID- 11338493
TI  - Effect of whitening agents on dentin bonding.
AB  - BACKGROUND: Several studies have shown a reduction in enamel bond strengths when
      the bonding procedure is carried out immediately after vital bleaching with
      peroxides. This reduction in bond strengths has become a concern in cosmetic
      dentistry with the introduction of new "in-office" and "waiting-room" bleaching
      techniques. The aim of this in vitro study was to evaluate the effect of three
      bleaching regimens: 35% hydrogen peroxide (HP), 35% carbamide peroxide (CP), and
      10% CP, on dentin bond strengths. MATERIALS AND METHODS: One hundred and twenty
      fresh bovine incisors were used in this study. The labial surface of each tooth
      was ground flat to expose dentin and was subsequently polished with 600-grit wet
      silicon carbide paper. The remaining dentin thickness was monitored and kept at
      an average of 2 mm. The teeth were randomly assigned to four bleaching regimens
      (n = 30): (A) control, no bleaching treatment; (B) 35% HP for 30 minutes; (C) 35%
      CP for 30 minutes; and (D) 10% CP for 6 hours. For each group, half of the
      specimens (n = 15) were bonded with Single Bond/Z100 immediately after the
      bleaching treatment, whereas the other half was bonded after the specimens were
      stored for 1 week in artificial saliva at 37 degrees C. The specimens were
      fractured in shear using an Instron machine. RESULTS: For the groups bonded
      immediately after bleaching, one-way analysis of variance (ANOVA) followed by the
      Duncan's post hoc test revealed a statistically significant reduction in bond
      strengths in a range from 71% to 76%. For the groups bonded at 1 week, one-way
      ANOVA showed that group B (35% HP for 30 min) resulted in the highest bond
      strengths, whereas 10% CP resulted in the lowest bond strengths. Student's t-test
      showed that delayed bonding resulted in a significant increase in bond strengths
      for groups B (35% HP) and C (35% CP); whereas the group bleached with 10% CP
      (group D) remained in the same range obtained for immediate bonding. Storage in
      artificial saliva also affected the control group, reducing its bond strengths to
      53% of the original.

PMID- 11338494
TI  - Evaluating porcelain color match of different porcelain shade-matching systems.
AB  - PURPOSE: This in vitro study was designed to evaluate the new ShadeEye-EX Chroma
      Meter and a new visual porcelain shade-matching system (Vitapan 3-D Master, Omega
      900) in comparison to the traditionally used visual porcelain shade-matching
      system (Vita Lumin Vacuum, VMK 68). MATERIALS AND METHODS: Shade matches and
      porcelain fabrications on individualized shade tabs were carried out. The
      fabricated porcelain tabs were evaluated against the respective natural tooth
      using the United States Public Health Service (USPHS) criteria to determine
      clinically acceptable match. The tabs also were ranked according to the final
      color match to the corresponding natural tooth. RESULTS: The percentage of
      clinically acceptable color matches were as follows: Vita Lumin Vacuum (46.67%),
      ShadeEye-EX (40%), and Vitapan 3-D Master (56.67%). The generalized estimating
      equation (alpha = 0.5) showed no statistically significant difference between
      systems in obtaining a clinically acceptable match (p = .5729). The chi-squared
      test (alpha = 0.5) showed no statistically significant difference between systems
      in terms of rank order (p = .5017). The two new systems do not produce color
      match that is better than the conventional visual porcelain shade-matching
      system.

PMID- 11338495
TI  - Esthetic dentistry--the future.

PMID- 11338496
TI  - [Experience in using phytopreparations to prevent and correct inflammatory
      urinary tract diseases].
AB  - The waste of some fruits, berries, and vegetables, which are accumulated by food
      industries (juice-extracting, wine, confectionery, and other industries) and
      generally completely utilized was pharmacognistically and phytochemically
      analyzed. The phytochemical analysis showed that the study objects (black
      currant, raspberry, viburnum, red and black mountain ashes, and grape fruit
      bagasses and melon, squash, and tomato seeds) contain a lot of lipophilic
      fractions (fatty oil) that present a complex of valuable biologically active
      substances. The developed recipes of phytopreparations are safe-and-easy-to-use
      and can be successfully used in patients with chronic inflammatory uterine
      appendage diseases and in those who present a difficult cohort of patients with
      lower urinary tract dysfunctions which are hardly correctable and require
      sophisticated choice of adequate drug therapy.

PMID- 11338497
TI  - [Prevention of lithogenesis in cholecystitis].
AB  - To treat and prevent cholelithiasis is one of the pressing problems facing modern
      medicine. A Vega MPT-705 apparatus was used to treat 52 patients with different
      forms of cholecystitis. Matrix regenerating therapy that had effects at cellular
      and subcellular levels was found to arrest an acute inflammation in the
      gallbladder wall, to normalize the physicochemical parameters of bile. It was
      concluded that the Vega MPT-705 apparatus could treat acute cholecystitis and
      hence prevent cholelithiasis.

PMID- 11338498
TI  - [Descending rhythmic pneumocompression as a medical treatment of atherosclerosis
      obliterans].
AB  - About 2 percent of the population of the world suffers from atherosclerotic
      lesion of the lower extremity arteries. However, the treatment of this pathology
      is an unsolved problem so far. The authors used a method of rhythmic
      pneumocompression for medical treatment of patients with chronic arterial
      insufficiency due to lower extremity vascular atherosclerosis obliterans. A total
      of 56 patients with stages II-III atherosclerotic lesion were examined. The
      findings indicated that the method noticeably reduced the intensity of the pain
      syndrome and tissue ischemia. The procedure exerted a reflex action on the
      cardiovascular system: the patients had slower heart rate and lowered blood
      pressure.

PMID- 11338499
TI  - [Unification of methods for determining the trace quantities of lead, zinc,
      sodium and potassium ions in the assessment of drinking water adn transfusion
      fluid quality].
AB  - The results of long-term studies made by the Department of General Chemistry, I.
      M. Sechenov Moscow Medical Academy, that deals with unification of methods for
      determining some ions of metals (lead, zinc, sodium, and potassium) in the
      assessment of the quality of drinking water and transfusion fluids are
      summarized. A procedure was developed to determine the trace impurities of zinc,
      lead, and silver by atomic absorption spectrometry (AAS) by using sorption
      concentration. C-80-2-aminothiazole, a new sorbent synthesized at the Research
      Institute of Polymers, was used to detect these ions in the drinking water. With
      regards to the chosen optimal conditions, drinking water samples were analyzed
      via their direct spraying in the air-acetylene flame. The prior sorption
      concentration determined drinking water zinc and lead ions in the concentrations
      equal to or less than their permissible dose concentrations. The studies
      indicated that the used methods to determine the trace quantities of metals in
      the drinking water and aqueous solutions show a high sensitivity, rapidity,
      simplicity of sample preparation.

PMID- 11338501
TI  - [Serum DNAse activity induction as a mechanism of infection resistance in man and
      animals].

PMID- 11338500
TI  - [Immunosuppressive effects of pathogenic gram-negative bacteria].
AB  - The review deals with the Immunosuppressive effects of virulent gram-negative
      bacteria (Salmonella, Shigela, Pseudomonas aeruginosa), with the importance of
      these effects for the bacteria to survive in the infected body. The above
      bacteria affect the immunity system in a different way, yet have common features.
      They are characterized by the occurrence of endotoxin shock, by the suppression
      of the phagocytic system and cell-mediated immunity. A significant role in
      suppressing a cellular immune response is played by the lipopolysaccharide of
      virulent bacteria that greatly differs from that of nonvirulent strains. The
      immunosuppressive activity of the bacteria and their lipopolysaccharide is
      closely related to their virulent properties.

PMID- 11338502
TI  - [The yeast malassezia on the skin of healthy individuals and patients with atopic
      dermatitis].
AB  - The lipophilic yeast Malassezia spp. from the skin of 32 healthy individuals and
      21 patients with atopic dermatitis was isolated and identified. Malassezia
      sympodialis was shown to be most common in both groups, M. Globosa was less
      frequently encountered. Moreover, no Malassezia was found in 34 and 53% of cases,
      respectively. There was a relationship of the skin colonization of Malassezia to
      the patients' age. Malassezia spp. cultures whose appurtenance was impossible to
      identified by the Guillot-Gueho method were detected.

PMID- 11338503
TI  - [Group A streptococcus-induced diseases early in the 21st century: state of the
      problem and prospects of prevention].
AB  - The review presents the present state of the problem due to the diseases caused
      by group A streptococci. Greater interest in streptococcal infections is
      associated with a recent rise in the incidence of these diseases in many
      countries of the world, including Russia, with group cases of severe generalized
      forms and higher death rates being notified. Of priority significance in human
      diseases are serogroup A beta-hemolytic streptococci among which there are those
      that have returned into the circulation of defunct pathogen serotypes that are
      noteworthy for higher toxigenicity. The specific feature of a streptococcal
      infection is the cyclic character of an epidemic process: in parallel with 2-4
      year periods there are also 40-50-year cycles. The undulation found is attended
      by the appearance and disappearance of particularly severe clinical forms of
      streptococcal infections. Immunodiagnostic techniques based on the determination
      of specific antibodies to streptococcal antigen has enjoyed the widest
      application in diagnosing streptococcal infections today. The therapeutical
      measures include the use of etiotropic and pathogenetic agents and direct toward
      eradication of the infecting organism and towards prevention of pyoinflammatory
      and autoimmune complications. Penicillin is the drug of choice in treating all
      forms of streptococcal infections. Despite progress in streptococcal vaccine
      design, there is no specific prophylaxis of streptococcal infection now, which
      determines the high value of antiepidemic measures.

PMID- 11338504
TI  - [Relationship of different risk factors of ischemic heart disease].
AB  - The spread of ischemic heart disease (IHD) risk factors, such as obesity,
      smoking, inactivity is discussed. Their relationship with the values of the serum
      lipid spectrum was examined. A wide spread of IHD risk factors and a low
      awareness of their implication were found in the population. The former can be
      reduced by questionnaire survey, interpretation of the presence of individual
      risk factors, and evaluation of the total risk of IHD. Sanitary and educational
      work on the pathogenesis of IHD is required for its successful prevention.

PMID- 11338506
TI  - [Catalytically active antibodies and their expected biological function].

PMID- 11338507
TI  - [Pathogenetic mechanisms of primary arterial hypertension in children and
      adolescents].

PMID- 11338505
TI  - [Molecular diagnosis of multiple type 2 endocrine neoplasia].
AB  - The paper reviews the data on the molecular structure of the protooncogene RET
      encoding for receptor-type protein kinase, on the mechanism of transformation of
      the normal protooncogene RET to a dominant transforming oncogene, and on RET
      mutations detected in patients with the MEN-2 syndrome. Moreover, it presents the
      authors' own findings. The familial medullary thyroid carcinoma burdened
      genealogy shows a new point mutation TCG(Ser)-->GCG(Ala) in codon 891, in the
      exon 15 of the protooncogene RET. This mutation was not detected in the
      chromosomes of healthy individuals. Analyzing the linkage with two known and two
      new polymorphic markers showed that there was a cisaggregation of informative
      polymorphic markers, phenotypic manifestation of the disease, and mutations in
      the genealogy in question. In the protooncogene RET, there were two new
      polymorphisms: G/A at position 24 in intron 14 and C/T in codon 836 (exon 14).
      The rate of the polymorphism encountered in codon 836 proved to be similar for
      the Russians and the Germans (0.96%), which was also seen for two earlier
      described polymorphisms in codon 691 (0.80 and 0.81, respectively) and in codon
      904 (0.21 and 0.22). At the same time, there were statistically significant
      differences in the rates of intron 14 polymorphism (0.87 and 0.77, respectively).
      In a family having MEN 2, a proband displayed TGC-->CGC mutation in codon 634 of
      the gene RET in the heterozygous state. The mutation results in substitution of
      cysteine amino acid residue in the cysteine-rich extracellular domain of protein
      kinase encoded by the gene RET for arginine. The results of molecular analysis
      were used to confirm its clinical diagnosis and to indicate that effective care
      should be delivered in MEN 2a.

PMID- 11338508
TI  - [Opportunistic microorganisms in urinary tract diseases].
AB  - The microflora of clinical material (urine, urethral discharge and smear, vaginal
      discharge and smear, feces in colonic dysbacteriosis) from patients with urinary
      tract infections (UTI) in the Moscow Region was studied. Escherichia coli and
      Staphylococcus epidermidis have been found to be the most common agents isolated
      from the urine of UTI patients. Pseudomonas aeruginosa and other staphylococcal
      species and enterococci account for a smaller proportion of infections. High- (E.
      coli and S. epidermidis) and moderate-priority pathogens are translocated into
      the urinary tract from the colonic biotope in dysbacteriosis. The causative
      agents of non-gonococcal urethritis are staphylococci (more commonly epidermal
      ones) in 50% of cases, those of pyelonephritis are staphylococci (predominantly
      E. coli) in more than 50% of cases. The etiological agents of female genital
      infections are staphylococci (mainly epidermal ones) in 40% of cases.

PMID- 11338509
TI  - [Oxygen transport parameters in halothane and isoflurane anesthesia with the low
      gas flow in children].
AB  - The efficiency and safety of low flow inhalation anesthesia for children were
      evaluated on the basis of oxygen transport parameters. Sixty-seven children aged
      3 months to 15 years (mean age 5.7 +/- 2.5 years) were subjected to inhalation
      halothane and isoflurane anesthesia with fresh gas flow of 0.5 liter/min. Oxygen
      delivery, consumption, and tissue extraction were evaluated. Oxygen transport
      parameters remained optimal at all stages of anesthesia, which confirmed the
      safety of this method in children for routine interventions.

PMID- 11338510
TI  - [Evaluation of aqueous compartments of the body by integral bioimpedance
      spectrometry in x-ray surgical interventions in children].
AB  - There were studied 14 children (mean age 5.71 +/- 0.60 years, body weight 18.95
      +/- 3.50 kg, height 101.0 +/- 4.03 cm) with initially normal osmotic and volumic
      status. Plasma osmolarity, blood aldosterone level, aqueous compartments balance
      were (evaluated by segmented bioimpedance spectrometry), urine osmolarity and
      diuresis were investigated after bolus injection of x-ray contrast agent (RCA)
      urografin-60% (mean volume 2 ml/kg for 2-4 sec). A statistically significant
      gradual decrease in the total volume of water (TVW) in the organism was observed,
      with 8.53% deficiency of TVW by the second hour after RCA injection in comparison
      with the initial level. TVW deficiency developed as the result of diuresis which
      increased 7-fold in the presence of increased plasma osmolarity after injection
      of RCA bolus. Correction of the volume of circulating blood and plasma was
      carried out mainly at the expense of intracellular liquid, whose deficiency was
      actually 4.5 times higher than of extracellular liquid. Bioimpedance spectrometry
      indicated centralized redistribution of water in the organism, as TVW deficiency
      was mainly due to water in the limbs. The results indicate the need in infusion
      therapy after RCA injection in order to correct the resultant water deficit.

PMID- 11338511
TI  - [Significance of tissue pH in the prognosis of postoperative complications in
      heart surgery patients].
AB  - Ischemia of the gastrointestinal mucosa is characterized by acidosis in the
      submucosal layer during the majority of interventions, which necessitates
      monitoring of tissue pH (pHi) of the abdominal organs during aortocoronary bypass
      surgery and the immediate postoperative period. The pHi was measured by
      gastrotonometry with a nasogastral tube (Trip catheter) and Tonocap-TC200 device
      (Datex Engstrom, Finland); pHi was measured in 17 patients in department of
      intensive care on days 1 or 2 after cardiosurgical interventions with at least
      120-min artificial circulation and in 23 patients during the operation. Surgical
      treatment consisted in correction of acquired valvular diseases, myocardial
      revascularization (shunting operations), and combinations of these operations.
      The first stage of investigation revealed a relationship between decreased pHi
      level to the acid values and complicated course of the postoperative period. The
      second stage showed that postoperative complications occurred in 27.2% cases only
      in patients subjected to long artificial circulation bypass (more than 120 min).
      The frequency of complications were 2-fold more in the patients with tissue
      acidosis (pHi < 7.35) during surgery than in patients with normal and alkaline
      pHi values. The following complications occurred: acute pancreatitis, acute
      peptic ulcer, acute renal and polyorgan failure. Comparative analysis of pHi and
      other metabolic markers of arterial blood showed a correlation between these
      parameters, but pHi was more specific for the diagnosis of tissue ischemia.
      Hence, a low invasive highly specific method of gaseous gastrotonometry helps
      evaluate the blood supply to abdominal organs during and after cardiac surgery
      with artificial circulation and predict postoperative gastrointestinal and grave
      systemic complications (sepsis, acute renal failure, and polyorgan failure).

PMID- 11338512
TI  - [Significance of anesthesiology and intensive care in the development of
      reconstructive surgery (as exemplified by the scientific school of the
      Academician B.V. Petrovskii)].
AB  - B. V. Petrovsky, the creator of one of the leading surgical schools, realized,
      that surgery cannot develop without anesthesiological and resuscitation support.
      He actively promoted measures which ensured rapid transformation of such branches
      as anesthesia and postoperative care into independent disciplines. Introduction
      of neuroleptanalgesia, high-quality artificial ventilation of the lungs,
      prolonged regional and combined anesthesia, protection of the myocardium and
      brain, bronchofibroscopy, extracorporeal detoxication, assisted circulation, and
      computer monitoring allowed the performance of the most sophisticated
      interventions on the heart, aorta, lungs, esophagus, liver and bile duct, and
      peripheral vessels. Progress in anesthesiology and reanimatology promoted the
      development of new trends in reconstructive surgery, such as repair microsurgery,
      organ transplantation, endovascular and endoscopic surgery.

PMID- 11338513
TI  - [Experience in the organization of anesthesiological care in disaster medical
      services].
AB  - Presents a total-systems approach to urgent anesthesiological care and discusses
      the organization and safety standards in the work of an anesthesiologist and
      intensive care specialist of aircraft medical teams within the system of medicine
      of disasters.

PMID- 11338514
TI  - [Characteristics of anesthesia in children operated on for extrahepatic portal
      hypertension].
AB  - Portocaval shunting reliably preventing hemorrhages from esophagogastric veins is
      most often used in surgery for extrahepatic portal hypertension (EPH) in
      children. Difficulties of anesthesia for this intervention consists in essential
      alteration of volume bloodflow as a result of massive outflow of deposited blood
      to systemic circulation through the new bypass. This necessitates search for an
      adequate method of general anesthesia and variants of infusion therapy for
      surgical venous shunting in children with EPH. Sixty-eight children aged 1-15
      years with the EPH syndrome were subjected to elective surgery under general
      analgesia (multicomponent balanced neuroanesthesia with evaluation of some
      hemodynamic and metabolic parameters). The proposed protocol of general
      anesthesia in combination with epidural analgesia by local anesthetics and
      promedole and infusion therapy in the hypervolemic hemodilution mode create the
      most favorable conditions for adaptation of hemodynamics to increased preloand.

PMID- 11338515
TI  - [Clinical picture of awakening after general anesthesia with midazolam, propofol,
      ketamine and fluothane in children treated at one-day ambulatory facility].
AB  - The study was carried out in 75 children aged 6-12 years with the physical status
      ASA I. The operations were performed on the lymphadenoid throat ring in a one-day
      setting. Awakening after anesthesia was evaluated by the following parameters:
      time between the end of intervention and extubation of the trachea, opening the
      eyes when asked, transportation from the operation room into the ward, and first
      dialogue with the doctor. A system of evaluating the level of recovery of
      respiration, motor activity, and consciousness by Aldret and Kroulik's score was
      used for objective assessment of the data. Postoperative pain and discomfort were
      evaluated using Hannallah's score in all age groups. The most rapid recovery of
      muscle tone, defense reflexes, and higher functions of the brain was observed in
      the patients anesthesized with propofol; adequate doses of narcotic analgetics
      during short-term interventions ensured satisfactory analgesia and psychological
      condition during the immediate postoperative period.

PMID- 11338516
TI  - [Ketamine pharmacokinetics and metabolism after bolus injection of X-ray contrast
      agents in roentgeno-endovascular interventions in children].
AB  - The study was carried out on 13 children (2-12 years) subjected to abdominal
      aortography. The children were divided into 2 groups. Changes in plasma
      concentrations of ketamine and its metabolism were evaluated during anesthesia
      after bolus injection of ionic highly osmolar and nonionic low-osmolar x-ray
      contrast agents (RCA). Injection of an RCA bolus was associated with a 2-fold
      more rapid drop of the anesthetic concentration in the blood, increase of renal
      clearance of ketamine and its metabolites; the osmotic effect of ionic highly
      osmolar and nonionic low-osmolar RCA on ketamine pharmacokinetics virtually did
      not differ.

PMID- 11338517
TI  - [Effects of ketamine and propofol on oxygen status and blood content of the brain
      in children].
AB  - Near infrared spectroscopy (NIRS) was used for noninvasive measurement of
      oxyhemoglobin (O2Hb) and total hemoglobin (tHb) in cerebral tissue and for
      evaluating local hemoglobin saturation with oxygen (rSO2) and cytochrome oxidase
      (Cytaa3) redox status in 68 children (6-14 years) during intravenous induction
      anesthesia with various anesthetics. Monoanesthesia with ketamine essentially
      increased the level of tHb and rSO2 and decreased the oxidized Cytaa3 fraction.
      Combined induction with ketamine and midazolame and propofol induction did not
      cause notable changes in the values of cerebral oxymetry.

PMID- 11338518
TI  - [Adequate analgesic sedation: an alternative to general anesthesia in ambulatory
      settings].
AB  - A tendency to treatment in an outpatient setting implies development and more
      often use to outpatient anesthesias. Improving of general anesthesia is to be
      supplemented by wider use of analgosedation, which causes less vital
      complications. Intravenous and noninvasive methods of analgosedation are
      described, their adequacy is evaluated, and indications for their use are
      defined.

PMID- 11338519
TI  - [Combined anesthesia with blockade of nn.dorsalis penis and inhalation
      anesthetics in surgery of the penis in children].
AB  - The studies were carried out in 21 patients with abnormalities of the penis
      (coronal and penile hypospadia, webbed penis) aged 5-15 years. Central
      hemodynamics, heart rate, and arterial pressure were evaluated at 6 stages of
      anesthesia and surgery. Premedication, induction, and maintenance anesthesia were
      carried out routinely. Laryngeal mask was used during maintenance anesthesia. The
      nn. dorsalis penis was blocked with 0.25% marcaine in a dose of 0.1 ml/kg for
      each side. The results indicate that penile blockade in combination with
      inhalation anesthesia is an effective method for anesthesiological protection of
      children operated on the penis.

PMID- 11338520
TI  - [Hemodynamic status of the mother and fetus in pregnant women with gestosis
      during abdominal delivery under different anesthesia methods].
AB  - Pregnants in the third trimester with medium- and severe gestosis were divided
      into 3 groups according to types of maternal and fetal hemodynamics: 1) controls
      (n = 58 pts); 2) eukinetic type (n = 54 pts); and 3) hypokinetic type (n = 55
      pts). Each group was subdivided into 3 subgroups according to administered types
      of anesthesia for cesarean section (epidural, spinal, and general). Central
      hemodynamics of the mother, fetus, and fetoplacental complex was studied. Use of
      different anesthesias in woman with normal pregnancy did not affect the
      hemodynamics, and therefore any type of anesthesia can be used in cesarean
      section. In pregnants with gestosis, the eukinetic hemodynamic and compensated or
      subcompensated placental insufficiency the optimal anesthesia was epidural and
      spinal. For pregnant with hypokinetic circulation and subcompensated or
      decompensated placental insufficiency epidural anesthesia is preferable.

PMID- 11338521
TI  - [Choice of the optimal scale for evaluation of the severity of sepsis in
      children].
AB  - Quantitative assessment of the severity of clinical status was carried out and
      prognostic values of PRISM III, PRISM, SOFA, APACHE II scores and scores proposed
      by A. Castellanos et al. and K. L. Goitein was evaluated in 105 children (2
      months-14 years) with sepsis. Clinical status evaluated in score during the first
      day of intensive care was correlated to the disease outcome. Sensitivity,
      specificity, expected values of positive and negative results were evaluated for
      each score and their discrimination capacity was assessed by ROC analysis. Use of
      quantitative scores (PRISM, PRISM III, SOFA, APACHE II, and A. Castellanos') is
      permissible for prospective evaluation of the efficiency of intensive care in
      children with sepsis, PRISM being the most informative.

PMID- 11338522
TI  - [Complex approach to selection of antibiotics in the treatment of children with
      peritonitis].
AB  - The author discusses rational antibiotic therapy of pyoseptic diseases in
      children as exemplified by peritonitis. An approach to selection of the optimal
      drug is developed, consisting in a rapid bacteriological and immunological
      analysis of the minimal volume of blood, which helps choose the most effective
      antibiotic, evaluate individual drug tolerance and dose with consideration for
      the immunotropic effect of the drug in patients with changed immune status so
      that no further correction is needed.

PMID- 11338523
TI  - [Evaluation of the effectiveness of various protocols of antibiotic prophylaxis
      and therapy in pancreatic necrosis].
AB  - The efficiency of various protocols of antibiotic prophylaxis and therapy (APT)
      used in 63 patients with pancreonecrosis is analyzed. Early treatment with
      carbapenemes is the most effective in disseminated infectious pancreonecrosis
      requiring obligatory surgical treatment. Drug efficiency is the key factor in
      choosing APT for intensive care of patients with destructive pancreatitis.

PMID- 11338524
TI  - [Experience in the use of needle peripheral venous catheters in children].
AB  - The use of peripheral venous catheters manufactured by Johnson & Johnson Medical
      Ltd. in children was evaluated in terms of painfulness of venipuncture and
      cannulation, number of attempts needed to succeed, convenience of handling, and
      duration of the cannulation period. The intravenous catheters of Johnson &
      Johnson Medical Ltd. minimized the pain of venipuncture and cannulation and
      proved to be safe and convenient for patients and nursing staff.

PMID- 11338526
TI  - [First experience in the use of isoflurane in minor surgical interventions in
      children].

PMID- 11338525
TI  - [Experience in administration of prolonged anesthesia in children].

PMID- 11338527
TI  - [Acute intermittent porphyria in the practice of anesthesiology and intensive
      care].
AB  - Acute intermittent porphyria (AIP) is a hereditary disease caused by disordered
      haem biosynthesis and characterized by paroxysmal exacerbations. It usually
      manifests in adult women. Provoking factors are pregnancy, alcohol, and
      "porphyrogenic" drugs. Grave attacks of AIP require urgent hospitalization in
      intensive care wards, rapid purposeful diagnosis and adequate therapy,
      determining the prognosis. The number of drugs should be minimized and drugs with
      a known porphyrogenic effect absolutely ruled out. A 35-year-old patient with the
      first episode of AIP is described; the disease eventuated in death after 2
      months.

PMID- 11338528
TI  - [Prolonged artificial ventilation of the lungs in the complex treatment of
      children with bronchopulmonary diseases concomitant with primary pulmonary
      hypertension and lung tissue fibrosis].

PMID- 11338529
TI  - [Use of hyperbaric oxygenation and methylene blue in the treatment of a 10-year
      old child with methemoglobin producer poisoning].

PMID- 11338530
TI  - [Diagnosis of acute renal failure in pediatric nephrology].
AB  - Acute renal insufficiency (ARI) complicated the course of the underlying process,
      including primary and secondary glomerulonephritis, interstitial nephritis,
      pyelonephritis, dysmetabolic nephropathies, urolithiasis, tubulopathies, renal
      congenitae defects and injuries in 136 of 1695 children with nephrological
      diseases hospitalized at Republican Pediatric Renal Center during the last
      decade. In 69.1% cases ARI developed by the renal type, in 23.5% cases was caused
      by prerenal factors, and rarely (in 7.4% cases) by postrenal factors. Renal ARI
      in children was caused by 5 causes, including glomerulonephritis (47%), acute
      tubular necrosis (19%), interstitial nephritis (14%), vascular disorders (11%)
      resultant from vasculitis, renal vein thrombosis, and acute crystalluria (9%)
      which developed in the presence of grave dysmetabolic nephropathy. Among three
      clinical variants of ARI the most severe was observed in renal ARI leading to
      grave endogenous intoxication and pronounced decompensation of renal function.
      More benign course of renal ARI caused by acute tubular necrosis or acute
      crystalluria differed significantly from prerenal ARI by a more pronounced
      endogenous intoxication, increased fractionated sodium excretion, and renal
      insufficiency index higher than 1.

PMID- 11338531
TI  - [Anesthetics and the developing heart].
AB  - Effects of various anesthetics on the myocardium of developing heart are
      reviewed. Anesthetics suppress myocardial contractility in a fetus and newborn
      more intensively than in an adult. This is due to immature cell mechanisms
      regulating cardiomyocyte contractile activity and specific effect of the
      autonomic nervous system on the heart. It is obvious that the problem of
      interactions between anesthetics and developing cardiovascular system remains
      important because of constant introduction of new drugs with new cell and organ
      effects into practical anesthesiology.

PMID- 11338532
TI  - [Role of nitric oxide as a regulator of cell processes in the formation of
      multiple organ failure].
AB  - Main aspects of functional activity of nitric oxide (NO) are discussed.
      Physicochemical properties of NO, routes of its formation in man, and mechanism
      of its effects on physiological processes are described. In human body NO is
      formed as a result of activity of a specific enzyme, nitric oxide synthase. Three
      isoforms of the enzyme are known: neuronal, inducible, and endothelial. NO
      regulates vascular tone, cell adhesion, neurotransmission, bronchodilatation, and
      platelet aggregation. NO can protect and damage cells under different conditions.
      The effect of NO can be direct and mediated. Mechanisms of vasodilating effect of
      NO and of its effect on apoptosis are discussed. The role of NO in regulation of
      the functional activity of hepatocytes is described. Regulation of NO level in
      human organism is discussed.

PMID- 11338533
TI  - [Diagnostic criteria of carbohydrate metabolism disorders in pulmonary
      tuberculosis complicated by diabetes mellitus in patients with various
      haptoglobin phenotypes].
AB  - A total of 180 patients with various haptoglobin (Hp) phenotypes were examined in
      order to detect specific features of carbohydrate metabolism disorders in
      pulmonary tuberculosis concomitant with diabetes mellitus. Blood sugar levels, G
      6-PDH and LDH, acid-base balance, and 2,3-DPG and HbA1c were evaluated. LDH
      activity was decreased 1.3-1.7 times in comparison with the norm, G-6-PDH was
      decreased by 15-45% vs. the norm in 87% patients, acid-base status was
      imbalanced, HbA1c content was increased 1.5-1.7 times vs. the norm, and 2.3-DPG
      content was increased 2-3-fold in comparison with the norm in 83% patients.
      Increased levels of HbA1c and 2,3-DPG in the studied combination of diseases
      augmented disorders of O2 binding to hemoglobin, which led to hypoxia. The most
      pronounced shifts in the studied parameters were observed in patients with Hp 2-2
      and Hp 1-1. Changes in the studied parameters should be used for the diagnosis of
      the severity of carbohydrate metabolism disorders in diabetics with pulmonary
      tuberculosis.

PMID- 11338534
TI  - [Evaluation of the use of isoelectrofocusing method for measuring glycated
      hemoglobin].
AB  - Measurement of HbA1c is important for the diagnosis of early forms of diabetes
      mellitus, hemolytic and sickle-cell anemia, as it can be used for optimal and
      permanent monitoring of hyperglycemia and serve as an indicator of hemolysis
      process. Isoelectrofocussing method (IEF) was modified for measuring HbA1c in
      polyacrylamide gel (pH 3.5-9.5) on an LKB multiphore (Sweden). HbA1c was measured
      in 350 patients with diabetes mellitus, sickle-cell and hemolytic anemia, and in
      120 donors. In diabetics the mean content of HbA1c was 9.2 +/- 1.2%, in patients
      with hemolytic anemia 3.8 +/- 0.2%, and in patients with sickle-cell anemia 3.9
      +/- 0.28%, vs. the normal value of 5.2 +/- 0.13%. Hence, our experiments
      demonstrated the possibility of wide use of IEF in our modification for
      identification of the above diseases in clinical laboratory.

PMID- 11338535
TI  - [Determination of HIV RNA concentration for evaluation of the efficacy of
      combined therapy of HIV infection].
AB  - Plasma HIV RNA (viral load) and count of CD4+ T cells were evaluated in 23
      patients with HIV infection treated with invirase (1800 mg/day), zidovudine (600
      mg/day), and zalcitabine (2.25 mg/day) for 6 months in order to evaluate the
      efficiency of antiretroviral therapy. Viral load was measured by AMPLICOR HIV-1
      Monitor test. The reproducibility of HIV RNA measurements was in line with
      reported data (CV 15-41%), allowing highly accurate (15%) evaluation of RNA in a
      standard control sample provided by National Institute for Biological Standards
      and Control, Great Britain. Plasma HIV RNA concentration decreased to an
      undetectable level (below 400 RNA copies/ml plasma) after 6 months of treatment
      in 52.2% patients. In 17.4% the therapy failed, and in 30.4% it resulted in a
      reduction of viral load to > 1 lg, although HIV RNA was still detected in the
      plasma after 6-month therapy. The count of CD4+ T cells increased by 9.5%.
      Changes in the viral load outstripped changes in CD4+ cells. Viral load was in
      high correlation with the count of CD4+ lymphocytes: -0.53, p = 0.01 before
      treatment and -0.61, p = 0.002 after 6-month treatment.

PMID- 11338536
TI  - [Prenatal diagnosis of cytomegalovirus infection].
AB  - Prognostic value of markers of cytomegalovirus infection (CMV) in pregnant women
      for the neonatal status was assessed. Detection of such markers as antiCMV IgM
      and CMV DNA in cervical secretion by DNA dot-spot hybridization in women with a
      complicated course of pregnancy indicates a 5.7% risk of delivery of children
      with stable symptoms. Studies of antibodies to pre-early proteins (IE CMV) showed
      that antiCMV IgG to IE are more incident in pregnant women than antiCMV IgM;
      moreover, antiCMV IgG to IE but not antiCMV IgM are detected in umbilical blood.
      The results of detection of antiCMV IgG and IgM to IE correlated with the
      clinical characteristics of newborns.

PMID- 11338537
TI  - [Laboratory diagnosis of toxoplasmosis using polymerase chain reaction].
AB  - Polymorphism of clinical manifestations in Toxoplasma infection and variegated
      disease patterns virtually rule out the diagnosis based solely on clinical
      symptoms, which makes modern laboratory tests particularly important.
      Amplification test system based on the polymerase chain reaction has been
      developed for the diagnosis of Toxoplasma infection. Computer analysis of
      nucleotide sequence of Toxoplasma gondii surface antigen gene P30 was analyzed,
      which helped choose and synthesize specific oligonucleotide primers. A method for
      biological material processing was selected, allowing sufficient DNA output.
      Optimal conditions for amplification reaction, ensuring absolute specificity and
      high (10-100 cells/sample) sensitivity, were determined.

PMID- 11338538
TI  - [Laboratory diagnosis of HIV infection in children during the first year of life
      (lecture)].

PMID- 11338539
TI  - [Apolipoprotein E in transport and receptor absorption of saturated fatty acids
      by cells; facts and hypothesis (literature review)].

PMID- 11338540
TI  - [Laboratory diagnosis of hepatitis C].
AB  - Laboratory algorithm for the diagnosis of viral hepatitis C (HVC) is proposed.
      Blood sera are screened for antiHVC by third-generation EIA and PCR of HVC RNA.
      Positive result of PCR is diagnostically significant. In case of positive EIA and
      negative PCR the serum is to be analyzed in immunoblotting. If immunoblotting is
      not carried out, the diagnosis is made on the basis of estimated values of
      hepatitis C probability attached to diagnostic EIA kit used in clinical
      laboratory. When evaluating the positive result, the increase in optic density
      (OD) of analyzed samples is compared with the cutoff OD. In OD higher than 9 and
      below 1.5 the probability of disease is 92.6 and 11.8%, respectively. Patients
      with doubtful results of serological tests are to be regularly checked up for 1
      year, with laboratory tests (immunoblotting and PCR) repeated every 3 months.
      Complex laboratory diagnosis by biochemical and serological methods and PCR
      should be carried out in groups at a high risk of HVC.

PMID- 11338541
TI  - [Comparative analysis of methods of diagnosis of chlamydia infection].
AB  - In case of a correct sampling, the diagnostic value of optic and electron
      microscopy for detecting Chlamydia infection is not inferior to that of direct
      microimmunofluorescence (DMIF) and higher than that of enzyme immunoassay (EIA).
      Optic microscopy showed that basal vaginal epithelium and buccal mucosa can be
      infected with Chlamydia. Provazek bodies were detected in the buccal mucosa of
      the overwhelming majority of patients with genital chlamydiasis. These results
      were confirmed by DMIF and EIA. Since none of the diagnostic methods is 100%
      reliable, we recommend using two methods: inexpensive optic microscopy and
      polymerase chain reaction or DMIF.

PMID- 11338543
TI  - Using 'mystery shoppers' in evaluating performance of security officers.

PMID- 11338542
TI  - [Statistical quality control of clinical laboratory analyses using Chi squared
      criterion (use of computer modeling)].
AB  - Models of analytical series simulating good results and series with systematic
      errors were created on the basis of data bank of results of clinical biochemical
      analyses by computer simulation method. The quality of analyses was evaluated
      using chi 2 test. This parameter reacts to slight systematic errors and depends
      little on changes in the examined patient population; on the other hand, its
      sensitivity is the higher the longer is the analytical series. Statistical method
      for quality control by the chi 2 test is highly sensitive, absolutely objective,
      and requires no extra expenses for control studies.

PMID- 11338544
TI  - An interview with: Fredrick G. Roll on preparing in advance for security
      problems.

PMID- 11338545
TI  - Patient tries his own case; wins lawsuit charging negligent security.

PMID- 11338546
TI  - Med center: 22 years of experience with surveillance cameras.

PMID- 11338547
TI  - A look into the growing world of hospital security dept Web pages.
AB  - As more and more security professionals become computer savvy, a growing number
      of hospital police and security departments are now accessible on the Internet
      via home pages or complete web sites--some with Intranet capability. How some of
      your colleagues are using their web sites is described in this report. You can
      check out other hospital security Internet sites, thanks to a unique web page
      maintained by a security officer.

PMID- 11338548
TI  - After fire: hospital reviews communication, emergency planning policies.

PMID- 11338549
TI  - [A new variant of choanal polyps].
AB  - Seven cases of ethmochoanal polyps, a form of nasal polyps, originating from
      mucosa of the back ethmoidal labyrinth and lowering into the nasopharynx are
      described. Such polyps are diagnosed primarily by computed tomography and
      endoscopy of the nasal cavity. Histologically, ethmochoanal polyps are similar to
      other polyps from paranasal sinuses. Surgical treatment of ethmochoanal polyps is
      made under the control of endoscope via approach through the superior nasal
      passage. The polyp part situated in posterior compartment of the ethmoidal
      labyrinth was removed with a microdebrider. 1 to 3 year follow-up registered no
      cases of recurrence.

PMID- 11338550
TI  - [Specific aspects of rhinomanometry in children with nasal septum deformity in
      the region of absorbing part of the nasal valve].
AB  - Available are original data on rhinomanometry in children with nasal septum
      distortion in the anterior part. Nasal patency before and after anemisation of
      the mucosa was measured in health and disease. Pressure in collapse of the nasal
      valve in children is higher than in adults, while dynamic range of the valve
      action in growing flow of the inspired air is more noticeable. In distortion of
      the nasal septum at the level of the absorbing part of the nasal valve
      anemisation reduces the air flow while the dynamic range is not detected. It is
      discussed whether early surgical intervention in children under sparing approach
      to nasal structures is valid.

PMID- 11338552
TI  - [Peculiarities of hypoacusis in citizens of the East Siberia].
AB  - Hearing disorders are characterized for citizens of the East Siberia belonging to
      Europeoid or Mongoloid race. Interpopulation features of hypoacusis of various
      genesis and effects of natural-geographic and ethnic factors on hypoacusis
      manifestations in native Mongoloid and migrant Europeoid Siberian population are
      shown.

PMID- 11338551
TI  - [Acoustic characteristics of resonance after cavity surgery on the ear and their
      usage in variants of reconstructive operations].
AB  - Acoustic measurements were made of the external and middle ear resonance in
      health and disease in patients after radical surgery on the ear and in chronic
      perforative otitis media. It is shown that the absence of the posterior wall of
      the acoustic meatus deteriorates hearing acuity in the frequency 4000 Hz.
      Reconstructive surgery of this wall normalizes acoustic resonance of the ear. The
      value of bone-air interval on pure tone audiogram is different after cavity
      operation and perforation of the tympanic membrane. Characteristics of acoustic
      resonance of the ear are decisive for choice of reconstructive surgery.

PMID- 11338553
TI  - [A closed variant of staged tympanoplasty with mastoidectomy in patients with
      chronic purulent otitis media].
AB  - 127 case records were analysed retrospectively. All the patients had otitis media
      purulenta chronica and had undergone tympanoplasty (a closed variant). Regular
      revision of the trepanation cavity was performed in patients with cholesteatoma.
      Residual cholesteatoma was detected in 5 of 76 patients with cholesteatoma before
      the first operation, recurrent cholesteatoma occurred in 2 patients. Normal
      position of the neotympanic membrane and recovery of normal anatomy of the
      external acoustic meatus were achieved in 116 (91.3%) operated patients.
      Preservation or improvement of hearing were observed in all the patients. Bone
      air gap under 30 dB was obtained in 79%. Thus, the proposed variant of closed
      staged tympanoplasty is effective for sanation of the infection focus with
      subsequent hearing improvement.

PMID- 11338555
TI  - [The state of antigen-dependent immunity system in children with chronic
      tonsillitis].
AB  - 245 children aged 7-14 years with decompensated chronic tonsillitis were examined
      and treated in Anapa health resort. Before therapy the children had subnormal
      concentration of CD3+, CD4+/CD8+, elevated absolute and relative concentration of
      CD16+, low concentration of salivary IgA and SIgA combined with high serum IgM.
      The treatment brought a positive trend in the above indices, but CD16+, serum IgA
      and salivary SIgA remained higher than in controls. This may be explained by
      genetic predisposition of some children (primary defects of IgA and its secretory
      component synthesis), effects of autoimmune pathology, natural reaction to
      persistent viral infection.

PMID- 11338554
TI  - [Clinical laboratory characteristics of the course of local oropharyngeal
      diphtheria in patients with chronic tonsillitis].
AB  - Of 115 patients admitted to hospital in 1994-1997 for stomatopharyngeal
      diphtheria (SPD), 41(35.7%) patients had compensated chronic tonsillitis (CT),
      while 17(14.8%) patients had decompensated CT. The ENT examinations carried out
      from the first day of the hospitalization helped to establish CT diagnostic
      criteria in localized form of SPD. It is shown that CT in diphtheric patients,
      especially decompensated CT, delays regress of local symptoms, extension of
      microbiocenotic spectrum and stomatopharynx contamination, prolongs carriage of
      diphtheric corinobacteria.

PMID- 11338556
TI  - [Validation of application of elastic tamponade of the middle ear postoperative
      cavities].
AB  - It is shown that gauze turunda tamponade of the middle ear postoperative cavities
      provokes bacterial contamination and formation of the infection focus. Inflatable
      latex tampon and technique of tamponade of the postoperative middle ear cavities
      after hearing-preserving sanation operations on the temporal bone were designed
      and tested. They proved superior to the gauze turundas and allow to avoid
      bacterial contamination. Microscopic and histological studies confirmed that
      removal of the latex tampon is safe for the postoperative wound surface making
      postoperative relapse less probable.

PMID- 11338557
TI  - [Experience in the administration of vasobral in sensorineural vascular
      hypoasusis].
AB  - 24 patients with neurosensory hypoacusis of vascular genesis related to chronic
      cerebral vascular deficiency in the vertebrobasillar bed combined with cervical
      osteochondrosis were given basobral. The drug produced positive changes in
      neurological symptoms, lowered hearing thresholds in the range of high
      frequencies, improved cerebral hemodynamics and hearing afferentation at the stem
      level of the acoustic analyzer.

PMID- 11338558
TI  - [Current diagnostic and therapeutic principles in orbital rhinosinusitis
      complications].
AB  - 86 cases of orbital rhinosinusogenic complications (ORC) have been analysed. The
      authors suppose that severity of orbital lesion depends on purulent or non
      purulent inflammation and pre- or postseptal location of the process. In addition
      to adequate examination of general and local ORC symptoms it is necessary to
      conduct x-ray of the paranasal sinuses. Indications for ultrasound investigation
      and CT of the orbit and paranasal sinuses are formulated. A diagnostic algorithm
      is proposed for ORC identification and specification of therapeutic measures.

PMID- 11338559
TI  - [Radio wave bipolar submucous coagulation in the turbinates in hypertrophic
      rhinitis after submucosal resection of the nasal septum].

PMID- 11338560
TI  - [A variant of combined of local antibacterial and analgesic treatment of the
      inflammation of the pharyngeal mucosa].

PMID- 11338561
TI  - [The administration of sinupret in the treatment of acute sinusitis in children].

PMID- 11338562
TI  - [Septolete treatment of laryngeal and pharyngeal inflammation].

PMID- 11338563
TI  - [Sinupret in the treatment of nasal and paranasal sinus diseases].

PMID- 11338564
TI  - [Lethal outcome in a child with laryngeal tuberculosis].

PMID- 11338565
TI  - [Is the Jacobson's organ a rudiment?].

PMID- 11338566
TI  - [Issues of problematic education at clinical departments of a "narrow"
      specialization].

PMID- 11338567
TI  - [Cytokines production by immune system cells in patients with various forms of
      chronic rhinosinusitis].
AB  - Production of cytokines IL-1 beta, IL-8, TNF-alpha, IFN-alpha and IFN-gamma by
      blood cells and their level in paranasal sinus lavage fluid (LF) were studied in
      seventy two patients with chronic rhinosinusitis. It was found that in various
      forms of rhinosinusitis the production of proinflammatory cytokines is
      characterized by common features: IL-1 beta:IL-8:TNF-alpha averages 1:6.5:0.47.
      While in polypous rhinosinusitis synthesis of IFN-gamma was reduced. LF cytokine
      profile depends on the form of chronic rhinosinusitis. The polypous form,
      pyoinflammation, pyopolypous form are characterized by low concentration of TNF
      alpha, lack of IL-1 beta, low production of IL-1 beta and interferons alpha and
      gamma, respectively.

PMID- 11338568
TI  - [Medical education and the needs of human resources in the Hungarian health care
      system].
AB  - The strategic aims of medical education are discussing, from the view of the
      human resource demands in a modern healthcare system. The authors summarise the
      logical framework of medical functioning based on medical development and
      economical circumstances, and describe the role of personal skills in the daily
      work. Afterwards they discuss the development of medical education in the last
      three decades and present the tight connection between cognitive sciences and
      developing results mentioned above. The authors analyse some special points of
      the Hungarian medical faculties. In the conclusion they have shown the
      possibilities to support the Hungarian healthcare reform by the educational
      development.

PMID- 11338569
TI  - [Repeat thrombolysis in acute myocardial infarction].
AB  - During two years period (Jul. 97-Aug. 99) data of patients suffering from
      recurrent acute myocardial infarct within 6 days were compared by retrospective
      analysis. In this interval authors treated 58 patients with recurrent myocardial
      infarct. 22 patients were transmitted to a catheterisation lab, data of the other
      36 patients were compared. There were two treatment groups: 18 patients received
      repeated thrombolysis (IT group), and 18 patients got conventional therapy (HT
      group). In the thrombolytic group 15 patients received streptokinase infusion
      again, and urokinase infusion was administred in 3 patients at second time. The
      patients were not transferred to a cath lab, because of their older ages (10
      patients), or capacity problems (13 patients), or in absence of their signed
      consent (13 patients). Comparisons were made on the basis of non invasive
      diagnostic procedures (reperfusion signs suggested by ECGs and enzymatic changes,
      and left ventricular ejection fraction at discharge), bleeding rate, and
      frequency of recurring angina at the 3 months visit, and on the basis of
      mortality. Ejection fractions and reperfusion signs were better in the repeated
      thrombolytic group (time of maximal level ST elevation: IT 19.70 +/- 6.00 min, HT
      23.17 +/- 5.15 min, p = 0.26 NS; T wave inversion time within six hours: IT 168
      +/- 45.17 min, HT 170 +/- 58.99 min, p = 0.94; reperfusion arrhythmia: IT 7, HT
      3, p = 0.15; CK peak time: IT 16.89 +/- 6.94 hour, HT 20.00 +/- 6.72 hour, p =
      0.18 NS; CK-MB peak time: IT 12.22 +/- 7.19 hour, HT 16.67 +/- 6.17, hour, p =
      0.55; > 3 x CK peak time: IT 14.18 +/- 6.03 hour, HT 20.00 +/- 7.37 hour, p =
      0.06, > 3 x CK-MB peak time: IT 8.80 +/- 4.54 hour, HT 15.20 +/- 6.19 hour, p =
      0.02, ECHO EF: IT 48.53 +/- 6.81%, HT 43.14 +/- 4.90%, p = 0.02, Isotope
      ventriculography EF: IT 50.87 +/- 5.45%, HT 44.57 +/- 4.89%, p = 0.003), however
      the bleeding rate was moderately higher (minor bleeding: IT 7, HT 3, p = 0.15,
      major bleeding: IT 3, HT 1). The frequency of ischemic episodes at 3-month visit,
      and 3-month mortality were similar in the two groups (episodes of angina: IT 2.00
      +/- 1.57, HT 2.42 +/- 1.88, p = 0.55; mortality: IT 4, HT 6, p = 0.46). Repeated
      thrombolysis is an effective therapeutical tool in centres without cath lab-
      according to the risk-benefit ratio too--in the case of early repeated myocardial
      infarct.

PMID- 11338570
TI  - [Barrett esophagus in systemic sclerosis].
AB  - Systemic sclerosis is a generalized systemic autoimmune disorder frequently
      involving the oesophagus causing reflux oesophagitis in the majority of patients.
      Barrett's oesophagus is one of the most serious complication of the reflux
      oesophagitis, in which the normal oesophageal squamous epithelium is partially
      replaced by metaplastic columnar epithelium. The clinical significance of
      Barrett's oesophagus is the significantly increased risk of developing the
      adenocarcinoma. In our paper, the authors present 5 cases with Barrett's
      oesophagus among their 52 examined patients with scleroderma.

PMID- 11338571
TI  - [Uterine artery embolization for the conservative management of leiomyoma].
AB  - Uterine leiomyoma, a benign, monoclonal tumor derived from a single myometrial
      cell, is one of the most frequent diseases in the female reproductive system.
      However, the factors involved in its initiation and growth remain poorly
      understood. Most commonly, it results in dysmenorrhea, menorrhagia, urinary tract
      and neurological symptoms, and abdominal distension. Additionally, it may cause
      infertility, late miscarriage or other severe complications in pregnancy. The
      conventional treatment for fibroids has been hysterectomy. However, many women do
      not like to lose their uterus and potential fertility. Myomectomy and medical
      treatment with GnRH analogue are accepted as alternative organ-conserving methods
      with limited efficacy. Selective embolization of uterine arteries might therefore
      have a significant role in the management of the disease. The purpose of this
      study was to determine the effectiveness of uterine embolization as primary
      therapy in the management of myomas. Uterine arterial embolization was performed
      in 3 patients with symptomatic leiomyomas. The uterus and fibroids were
      objectively evaluated with ultrasound and MRI. The efficacy and safety convinced
      the authors that this promising technique is at present the only reasonable
      alternative method in organ-conserving therapy. It is less invasive than surgery,
      it can restore fertility, it is well tolerated and the recovery time is shorter
      than that following surgical procedures. This preliminary experience is
      sufficient to encourage gynecologists to introduce the method in Hungary.

PMID- 11338572
TI  - [Endoscopic treatment of cholestasis caused by Ascaris lumbricoides].
AB  - The most common infection of the hepatobiliary system and of the pancreas is the
      infestation with Ascaris lumbricoides. Pancreatobiliary ascariasis may present as
      recurrent biliary colic, acalculous cholecystitis, cholangitis, pancreatitis, or
      hepatic abscess. Although ultrasonography is a highly sensitive and specific
      method for the detection of the disease, endoscopy may have also therapeutical
      potential. The majority of these infections is registered in developing
      countries, but the number of reports from Europe and North America is increasing.
      So far there has not been any publication from Hungary. Both of the two reported
      patients were admitted the hospital with colic pain in the right hypochondrium.
      The laboratory parameters revealed cholestasis. The transabdominal
      ultrasonography was normal in one case, but suspected alien body in the
      choledochus in the other patient. Ascaris lumbricoides was identified with
      endoscopic procedure in the ductus choledochus in both cases. Endoscopic
      extraction of the worm resulted in cessation of the complaints in both patients,
      their cholestatic laboratory parameters became normal. Although the parasitic
      tests in the stool were negative in both patients and in their relatives,
      mebendazole therapy was administered.

PMID- 11338573
TI  - [Contribution to the monography "Szentkiralyi Street Internal Medicine Clinic"].

PMID- 11338574
TI  - [Contribution to the problem of scientometry in Hungary].

PMID- 11338575
TI  - Direct profiling of multiple enzyme activities in human cell lysates by affinity
      chromatography/electrospray ionization mass spectrometry: application to clinical
      enzymology.
AB  - We describe a new method for enzyme analysis using affinity capture followed by
      electrospray ionization mass spectrometry (ACESIMS) for the quantitative
      determination of the initial velocities of four heparin-modifying enzymes. These
      enzymes, when defective in affected children, lead to the lysosomal storage
      disease known as Sanfilippo syndrome. The method relies on substrates and
      internal standards conjugated to the molecular handle biotin via a heavy isotope
      encodable, mass-adjustable linker. Reaction velocities of the Sanfilippo enzymes
      in a crude lysate prepared from as little as 2500 human skin fibroblasts can be
      determined. In addition, the ACESIMS method is widely applicable to the
      simultaneous analysis of multiple enzymes in a complex biological sample by a
      single analytical technique and will thus serve as a useful tool in basic and
      clinical biomedical research.

PMID- 11338576
TI  - Generation of multiple electrosprays using microfabricated emitter arrays for
      improved mass spectrometric sensitivity.
AB  - Arrays of microelectrospray emitters were fabricated on polycarbonate substrates
      using a laser etching technique. Stable multielectrosprays were successfully
      generated in the liquid flow rate range relevant to mass spectrometric
      applications. Comparison of electrosprays generated from the microfabricated
      emitter array and conventional fused-silica capillaries showed similar spray
      characteristics and reliability. Higher total electrospray ion currents were
      observed as the number of electrosprays increased at a given total liquid flow
      rate. Consistent with the theoretical prediction, the total spray current at a
      constant total liquid flow rate was shown experimentally to be approximately
      proportional to the square root of the number of electrosprays. It is further
      projected that when total flow rate is optimized the maximum achievable total
      current will be proportional to the number of emitters. Evaluation of the
      multielectrospray device using a triple quadrupole mass spectrometer showed a
      factor of 2-3 sensitivity enhancement for the spray numbers ranging from two to
      nine compared to a conventional single electrospray ionization source under the
      same operating conditions.

PMID- 11338577
TI  - Evaluation of opiate separation by high-resolution electrospray ionization-ion
      mobility spectrometry/mass spectrometry.
AB  - The separation of opiates and the primary metabolites was evaluated with ESI
      IMS/MS. Seven opiate molecules were analyzed, and spectra were shown for each
      compound. The IMS separation of two isomers (morphine and norcodeine) was shown
      with baseline separation. Differences in the mobilities were found for the
      nonacetylated, monoacetylated, and biacetylated compounds. In this study, two
      primary findings are reported. First, IMS can easily separate metabolic isomers,
      and second, the two-dimensional separation capability of IMS/MS can be employed
      to confidently identify and separate both the opiates and metabolites. Although
      previous IMS studies have shown the separation of isomers, this is the first
      example to show the capability of IMS to separate metabolic isomers (within 70
      s), a significant advantage in high-throughput screening for pharmacokinetic
      studies. Second, the monoacetylated and biacetylated compounds were found to form
      more compact ions for the sodium adducts in comparison to the protonated
      molecular ions. On the basis of the mobilities, information on structures and
      conformation can be deduced when sodium and protonated ions are compared.

PMID- 11338578
TI  - A CE-MALDI interface based on the use of prestructured sample supports.
AB  - We have developed an off-line coupling of capillary electrophoresis (CE) to
      matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry(MALDI-TOF-MS) based on CE fraction collection onto prestructured
      MALDI sample supports. Analyte carryover and detection sensitivity were
      investigated using a standard peptide mixture. Low femtomole amounts were
      detected, and no noticeable carryover was discovered. The performance of the
      method was evaluated with a mixture of tryptic digests of proteins from a human
      fetal brain cDNA expression library. The total number of identified peptides was
      increased from 47 to 211 when the CE-MALDI interface was used compared to direct
      MALDI-MS analysis. Sequence coverage with CE-MALDI was in the 25-60% range for
      the different proteins, corresponding to an increase of 1.3-4.9 times relative to
      that obtained with MALDI-MS of the crude mixture. Fractionation of sample
      components also facilitated protein identification by MALDI postsource decay
      analysis. Our initial results suggest this CE-MALDI interface can be used for the
      analysis of complex peptide mixtures isolated from biological tissues.

PMID- 11338579
TI  - SALSA: a pattern recognition algorithm to detect electrophile-adducted peptides
      by automated evaluation of CID spectra in LC-MS-MS analyses.
AB  - A pattern recognition algorithm called SALSA (scoring algorithm for spectral
      analysis) has been developed to rapidly screen large numbers of peptide MS-MS
      spectra for fragmentation characteristics indicative of specific peptide
      modifications. The algorithm facilitates sensitive and specific detection of
      modified peptides at low abundance in an enzymatic protein digest. SALSA can
      simultaneously score multiple user-specified search criteria, including product
      ions, neutral losses, charged losses, and ion pairs that are diagnostic of
      specific peptide modifications. Application of SALSA to the detection of peptide
      adducts of the electrophiles dehydromonocrotaline, benzoquinone, and iodoacetic
      acid permitted their detection in a complex tryptic peptide digest mixture. SALSA
      provides superior detection of adducted peptides compared to conventional tandem
      MS precursor ion or neutral loss scans.

PMID- 11338580
TI  - Enantiomeric analysis of pharmaceutical compounds by ion/molecule reactions.
AB  - Protonated complexes involving cyclodextrin hosts and guest compounds that are
      pharmacologically important are produced in the gas phase and reacted with a
      gaseous amine. The guest is exchanged to produce a new protonated complex with
      the amine. The reaction is enantioselective and is used to develop a method for
      determining enantiomeric excess using only mass spectrometry. The pharmaceutical
      compounds include DOPA, amphetamine, ephedrine, and penicillamine. The presence
      of more than one reacting species is observed with DOPA and penicillamine.
      Molecular dynamics calculations are used to understand the nature of the
      interactions and the possible source of the variations in the reactivities.

PMID- 11338581
TI  - Mass spectrometric quantitation of chiral drugs by the kinetic method.
AB  - A novel mass spectrometric method for rapid, accurate (2-4% ee) quantitation of
      chiral drugs is described. Copper(II)-bound complexes of seven model drugs
      (atenolol, DOPA, ephedrine, pseudoephedrine, isoproterenol, norepinephrine,
      propranolol) with chiral reference compounds (L-amino acids) are generated by
      electrospray ionization mass spectrometry. The trimeric complex ions (three
      chiral ligands--one of the analyte and two of the reference compound) are
      collisionally activated, and they undergo dissociation by competitive loss of
      either the neutral reference or the neutral drug molecule. The ratio of the two
      competitive dissociation rates, viz. the product ion branching ratio, is related
      via the kinetic method to the enantiomeric composition of the drug mixture. A two
      point calibration curve, derived from the kinetic method, allows rapid
      quantitation of enantiomeric excess of drug mixtures. The chiral sensitivity of
      the method is such as to allow determination of mixtures with a few percent
      enantiomeric contamination.

PMID- 11338582
TI  - Stabilization of gas-phase noncovalent macromolecular complexes in electrospray
      mass spectrometry using aqueous triethylammonium bicarbonate buffer.
AB  - The use of triethylammonium bicarbonate (TEAB) solution in electrospray mass
      spectrometry proved to be a very efficient way for studying proteins or
      noncovalent protein complexes under "nondenaturing" conditions. The low charge
      states observed in the mass spectra improve the separation of ions arising from
      macromolecular species of close masses. Moreover, the multiply charged ions
      generated in a TEAB solution are significantly more stable than those formed
      under more conventional conditions (for example, with ammonium bicarbonate or
      acetate solution). The analytical interest of TEAB for the analysis of
      macromolecular species that can easily dissociate in the gas phase, such as
      hemoglobin or other macromolecular noncovalent complexes, is demonstrated.

PMID- 11338583
TI  - Matrix-assisted laser desorption/ionization coupled with quadrupole/orthogonal
      acceleration time-of-flight mass spectrometry for protein discovery,
      identification, and structural analysis.
AB  - The design and operation of a novel UV-MALDI ionization source on a commercial
      QqoaTOF mass spectrometer (Applied Biosystem/MDS Sciex QSTAR Pulsar) is
      described. Samples are loaded on a 96-well target plate, the movement of which is
      under software control and can be readily automated. Unlike conventional high
      energy MALDI-TOF, the ions are produced with low energies (5-10 eV) in a region
      of relatively low vacuum (8 mTorr). Thus, they are cooled by extensive low-energy
      collisions before selection in the quadrupole mass analyzer (Q1), potentially
      giving a quasi-continuous ion beam ideally suited to the oaTOF used for mass
      analysis of the fragment ions, although ion yields from individual laser shots
      may vary widely. Ion dissociation is induced by collisions with argon in an rf
      only quadrupole cell, giving typical low-energy CID spectra for protonated
      peptide ions. Ions separated in the oaTOF are registered by a four-anode detector
      and time-to-digital converter and accumulated in "bins" that are 625 ps wide.
      Peak shapes depend upon the number of ion counts in adjacent bins. As expected,
      the accuracy of mass measurement is shown to be dependent upon the number of ions
      recorded for a particular peak. With internal calibration, mass accuracy better
      than 10 ppm is attainable for peaks that contain sufficient ions to give well
      defined Gaussian profiles. By virtue of its high resolution, capability for
      accurate mass measurements, and sensitivity in the low-femotomole range, this
      instrument is ideally suited to protein identification for proteomic applications
      by generation of peptide tags, manual sequence interpretation, identification of
      modifications such as phosphorylation, and protein structural elucidation. Unlike
      the multiply charged ions typical of electrospray ionization, the singly charged
      MALDI-generated peptide ions show a linear dependence of optimal collision energy
      upon molecular mass, which is advantageous for automated operation. It is shown
      that the novel pulsing technique of this instrument that increases the
      sensitivity for precursor ions scans is applicable to the identification of
      peptides labeled with isotope-coded affinity tags.

PMID- 11338584
TI  - High sensitivity Fourier transform ion cyclotron resonance mass spectrometry for
      biological analysis with nano-LC and microelectrospray ionization.
AB  - Modifications to a 7 T nano-LC micro-ESI FT-ICR mass spectrometer, including a
      shorter octopole, approximately 100% duty cycle, improved nano-LC micro-ESI
      emitter tips, and reverse-phase HPLC resins that require no ion-pairing agent,
      combine to achieve attomole detection limit. Three peptides in a mixture totaling
      500 attomoles (amol) each in water (10 microL, 50 amol/microL) are separated and
      detected, demonstrating detection from a mixture at low endogenous biological
      concentration. Two peptides in a mixture totaling 500 amol each in artificial
      cerebrospinal fluid (1 microL, 500 amol/microL) are separated and detected,
      demonstrating detection from a mixture at a biological concentration in a
      biological solvent. The highest sensitivity is attained with arg8-vasotocin, in
      which a total of 300 amol is detected in artificial cerebrospinal fluid (1
      microL, 300 amol/microL) and a total of 100 amol in water (1 microL, 100
      amol/microL). Arg8-vasotocin isolated from the pineal gland of rainbow trout is
      detected, demonstrating the ability of FT-ICR to detect and identify a true
      endogenous biological analyte.

PMID- 11338585
TI  - Characterization of poly(L-lactide)-block-poly(ethylene oxide)-block-poly(L
      lactide) triblock copolymer by liquid chromatography at the critical condition
      and by MALDI-TOF mass spectrometry.
AB  - Poly(L-lactide)-block-poly(ethylene oxide)-block-poly(L-lactide) triblock
      copolymers (PLLA-b-PEO-b-PLLA) were fractionated in terms of the number of LLA
      units by liquid chromatography at the critical condition (LCCC) of PEO block. The
      fractionated samples were identified using MALDI-TOF mass spectrometry. The
      dependence of the LCCC retention of the diblock and triblock copolymers on the
      degree of polymerization of PLLA block(s) follows Martin's rule very well. Unlike
      the case of PEO-b-PLLA diblock copolymer reported earlier (Lee, H.; et al.
      Macromolecules 1999, 32, 4143), however, a splitting of the elution peaks
      containing the same number of LLA units was found. The peak splitting was
      ascribed to the different length distributions of PLLA blocks at the two ends of
      the PEO block. From the relative intensities of the peaks, the split peaks were
      assigned to different isomeric structures of the PLLA blocks. From these results
      we conclude that the interaction of the triblock copolymers with the stationary
      phase is affected by the distribution of the interacting blocks at the two ends
      of the center PEO block, in addition to the total number of LLA units in the
      triblock copolymer.

PMID- 11338586
TI  - On-chip proteolytic digestion and analysis using "wrong-way-round" electrospray
      time-of-flight mass spectrometry.
AB  - Rapid protein digestion and analysis using a hybrid microchip nanoelectrospray
      device and time-of-flight mass spectrometry detection are reported. The device
      consists of a planar glass chip with microfabricated channels coupled to a
      disposable nanospray emitter. Reactions between substrate and enzyme (trypsin),
      mixed off-chip and then immediately loaded into a sample reservoir on the device,
      are monitored in real time following the onset of electrospray. Protein cleavage
      products are determined at the optimum pH for generating tryptic fragments,
      directly from the digestion buffer using "wrong-way-round" electrospray, i.e.,
      monitoring (MH)+ ions from basic solutions. Intense tryptic peptide ions are
      observed within a few minutes following sample loading on the microchip. Proteins
      were identified from low femtomole or even attomole quantities of
      analyte/spectrum using peptide mass fingerprinting, loading 0.1-2 pmol/microL of
      sample on the chip. The sequence coverage for analyzed proteins ranged from 70 to
      95%. The rapid analysis of human hemoglobin is demonstrated using the technique.

PMID- 11338587
TI  - Evaluation of a four-channel multiplexed electrospray triple quadrupole mass
      spectrometer for the simultaneous validation of LC/MS/MS methods in four
      different preclinical matrixes.
AB  - A four-channel multiplexed electrospray interface on a triple quadrupole mass
      spectrometer was evaluated for the simultaneous validation of LC/MS/MS methods
      for the quantitation of loratadine and its metabolite, descarboethoxyloratadine,
      in four different biological matrixes. The assays were performed in rat, rabbit,
      mouse, and dog plasma from 1 to 1000 ng/mL using 96-well solid-phase extraction
      for sample preparation. The limit of quantitation of 1 ng/mL corresponded to 5.56
      pg of each analyte injected on-column. For the drug, quality control samples (n =
      6 at four concentrations) had precision ranging from 0.967 to 16.0% and accuracy
      ranging from -8.44 to 10.5% across all four species. For the metabolite, the
      precision ranged from 0.684 to 11.0% and the accuracy was between 6.36 and 
      9.06%. Intersprayer cross talk for the multiplexed electrospray ion source was
      evaluated as a function of analyte concentration and was less than 0.08% at
      concentrations as high as 1000 ng/mL. These results demonstrate the feasibility
      of using parallel analysis to reduce the time required for method validation and
      to increase sample throughput in drug development studies.

PMID- 11338588
TI  - Velocity measurement of particles flowing in a microfluidic chip using Shah
      convolution Fourier transform detection.
AB  - A noninvasive radiative technique, based on Shah convolution Fourier transform
      detection, for velocity measurement of particles in fluid flows in a microfluidic
      chip, is presented. It boasts a simpler instrumental setup and optical alignment
      than existing measurement methods and a wide dynamic range of velocities
      measurable. A glass-PDMS microchip with a layer of patterned Cr to provide
      multiple detection windows which are 40 microns wide and 70 microns apart is
      employed. The velocities of fluorescent microspheres, which were
      electrokinetically driven in the channel of the microfluidic chip, were
      determined. The effects of increasing the number of detection windows and
      sampling period were investigated. This technique could have wide applications,
      ranging from the determination of the velocity of particles in pressure-driven
      flow to the measurement of electrophoretic mobilities of single biological cells.

PMID- 11338589
TI  - Covalently bound ionene polyelectrolyte-silica gel stationary phases for HPLC.
AB  - Micelle-mimetic ionene-based stationary phases for high-performance liquid
      chromatography (HPLC) are prepared by attaching [3,16]- and [3,22]-ionenes to
      aminopropyl silica through a carbon-nitrogen bond. These [x,y]-ionenes are
      polyelectrolytic molecules consisting of dimethylammonium charge centers
      interconnected by alternating alkyl chain segments containing x and y methylene
      groups, some of which can form aggregate species whose properties mimic those of
      conventional surfactant micelles. These ionene-bonded stationary phases were
      characterized using different recommended HPLC test mixtures. Test solute
      chromatographic behavior on the ionene phases was found to be similar to that of
      intermediate oligomeric or polymeric C-18 and/or phenyl phases, depending upon
      the specific test mixture employed. In addition, the phases exhibit significant
      solute shape recognition ability. The ionene stationary phases were successfully
      employed for the separation of the components of the recommended ASTM reversed
      phase test mixture, as well as for ortho-, meta- and para-disubstituted benzenes
      and other positional or geometric isomeric compounds. The ionene materials allow
      for chromatographic separations under either reversed-phase or ion-exchange
      conditions. The retention mechanism on these multimodal phases can occur by
      hydrophobic partitioning or electrostatic interactions, depending upon the
      characteristics of the components of the analyte mixture (neutral or anionic).
      The effects of alteration of the percent organic modifier, flow rate and
      temperature of the mobile phase on chromatographic retention and efficiency on
      these phases were briefly examined.

PMID- 11338590
TI  - Packed capillary reversed-phase liquid chromatography with high-performance
      electrospray ionization Fourier transform ion cyclotron resonance mass
      spectrometry for proteomics.
AB  - In this study, high-efficiency packed capillary reversed-phase liquid
      chromatography (RPLC) coupled on-line with high-performance Fourier transform ion
      cyclotron resonance (FTICR) mass spectrometry has been investigated for the
      characterization of complex cellular proteolytic digests. Long capillary columns
      (80-cm) packed with small (3-micron) C18 bonded particles provided a total peak
      capacity of approximately 1000 for cellular proteolytic polypeptides when
      interfaced with an ESI-FTICR mass spectrometer under composition gradient
      conditions at a pressure of 10,000 psi. Large quantities of cellular proteolytic
      digests (e.g., 500 micrograms) could be loaded onto packed capillaries of 150
      micron inner diameter without a significant loss of separation efficiency.
      Precolumns with suitable inner diameters were found useful for improving the
      elution reproducibility without a significant loss of separation quality. Porous
      particle packed capillaries were found to provide better results than those
      containing nonporous particles because of their higher sample capacity. Two
      dimensional analyses from the combination of packed capillary RPLC with high
      resolution FTICR yield a combined capacity for separations of > 1 million
      polypeptide components and simultaneously provided information for the
      identification of the separated components based upon the accurate mass tag
      concept previously described.

PMID- 11338591
TI  - DNA capillary electrophoresis in entangled dynamic polymers of surfactant
      molecules.
AB  - Aqueous solutions of monomeric nonionic surfactants, n-alkyl polyoxyethylene
      ethers (C16E6, C16E8, C14E6), can be used as sieving matrixes for the separation
      of DNA fragments by capillary electrophoresis. Unlike ordinary polymer solutions,
      these surfactant solutions behave as dynamic polymers. By combining the
      "reversible gel" theory of DNA electrophoresis and the static and dynamic
      properties of wormlike surfactant micelles, a model is developed for describing
      the migration behavior of DNA molecules in these solutions. According to the
      model, the separation limit can be extended at low surfactant concentrations.
      Surfactant solutions as a separation medium provide many advantages over ordinary
      polymers, such as ease of preparation, solution homogeneity, stable structure,
      low viscosity, and self-coating property for reducing electroosmotic flow. More
      importantly, the properties of wormlike micelles (micelle size, entanglement
      concentration) can be adjusted by simply changing the monomer concentration,
      denaturant, and temperature to allow the separation of different size ranges of
      DNA fragments. Fast separation is achieved for DNA fragments ranging from 10 bp
      to 5 kb by using bare fused-silica columns. DNA sequencing fragments of BigDye G
      labeled M13 up to 600 bases were separated within 60 min.

PMID- 11338592
TI  - Robust polymeric microchannel coatings for microchip-based analysis of neat PCR
      products.
AB  - Several silica coatings have been evaluated for replicate PCR product analysis in
      capillaries and electrophoretic microchips. Silica coatings are an essential
      component to many electrophoretic separations, and this importance is magnified
      in microchips, where separation distances are minimized. Increasing the
      resistance of coatings to separation conditions improves the reproducibility and
      longevity of the coated microchip, which allows for the full potential of these
      devices (rapid separations, high through-put, and longevity) to be realized. In
      this study, several coating parameters have been evaluated experimentally and
      through the literature to produce a coating with high resistance to the
      separation conditions of interest, neat PCR product separations. Coating
      degradation induced under these conditions was tested for several coatings, and
      the influence of surface hydroxylation, surface hydration, silanization solvent,
      silanizing reagent, catalysis, endcapping, and polymerization procedure are
      discussed. Under the testing conditions, a coating (coating E) prepared by
      silanization with chlorodimethyloctylsilane in toluene with a polymer layer of
      poly(vinylpyrrolidone) attached by a hydrogen abstraction method [Srinivasan, K.;
      Pohl, C.; Avdalovic, N. Anal. Chem. 1997, 69, 2798-2805] was most resistant. This
      coating was tested for longevity on electrophoretic microchips and was compared
      to the traditional coating of polyacrylamide. The coatings produced similar
      resolution and efficiencies; however, coating E provided more reproducible
      migration times and had performed for 635 analyses when testing was terminated.
      This procedure provides a reproducible, resistant surface coating, thus allowing
      for replicate analysis of neat PCR product on microchips.

PMID- 11338593
TI  - Molar mass profiling of synthetic polymers by free-solution capillary
      electrophoresis of DNA-polymer conjugates.
AB  - The molar mass distribution of a polymer sample is a critical determinant of its
      material properties and is generally analyzed by gel permeation chromatography or
      more recently, by MALDI-TOF mass spectrometry. We describe here a novel method
      for the determination of the degree of polymerization of polydisperse, uncharged,
      water-soluble polymers (e.g., poly(ethylene glycol) (PEG)), based upon single
      monomer resolution of DNA-polymer conjugates by free-solution capillary
      electrophoresis. This is accomplished by end-on covalent conjugation of a
      polydisperse, uncharged polymer sample (PEG) to a monodisperse, fluorescently
      labeled DNA oligomer, followed by electrophoretic analysis. The monodisperse,
      charged DNA "engine" confers to each conjugate an equal amount of electromotive
      force, while the varying contour lengths of the uncharged, polydisperse polymers
      engender different amounts of hydrodynamic drag. The balance of electromotive and
      hydrodynamic forces enables rapid, high-resolution separation of the DNA-polymer
      conjugates as a function of the size of the uncharged PEG tail. This provides a
      profile of the molar mass distribution of the original polymer sample that can be
      detected by laser-induced fluorescence through excitation of the dye-labeled DNA.
      We call this method free solution conjugate electrophoresis (FSCE). Theory-based
      analysis of the resulting electrophoresis data allows precise calculation of the
      degree of polymerization of the PEG portion of each conjugate molecule. Knowledge
      of the molecular mass of the uncharged polymer's repeat unit allows for direct
      calculation of the molar mass averages as well as sample polydispersity index.
      The results of these analyses are strikingly reminiscent of MALDI-TOF spectra
      taken of the same PEG samples. PEG samples of 3.4-, 5-, and 20-kDa nominal
      average molar mass were analyzed by FSCE and MALDI-TOF; the values of the molar
      mass averages, Mw and Mn, typically agree to within 5%. Measurements and molar
      mass calculations are performed without any internal standards or calibration.
      Moreover, when DNA-polymer conjugate analysis is performed in a chip-based
      electrophoresis system, separation is complete in less than 13 min. FSCE offers
      an alternative to MALDI-TOF for the characterization of uncharged, water-soluble
      polymers that can be uniquely conjugated to DNA.

PMID- 11338594
TI  - Capillary electrophoresis microchips for separation and detection of
      organophosphate nerve agents.
AB  - A miniaturized analytical system for separating and detecting toxic
      organophosphate nerve agent compounds, based on the coupling of a micromachined
      capillary electrophoresis chip with a thick-film amperometric detector, is
      described. Factors influencing the on-chip separation and detection processes
      have been optimized. Using a MES buffer (20 mM, pH 5.0) running buffer, a 72-mm
      long separation channel, and a separation voltage of 2000 V, baseline resolution
      is observed for paraoxon, methyl parathion, fenitrothion, and ethyl parathion in
      140 s. Such miniaturization and speed advantages are coupled to submicromolar
      detection limits and good precision. Applicability to spiked river water samples
      is demonstrated, and the implications for on-site environmental monitoring and
      rapid security screening/warning are discussed.

PMID- 11338595
TI  - Indirect laser-induced fluorescence detection for capillary electrophoresis using
      a violet diode laser.
AB  - The violet (415 nm) diode laser is used for indirect laser-induced fluorescence
      detection in capillary electrophoretic separations of inorganic anions and
      chemical warfare agent degradation products. Inorganic anions were detected using
      8-hydroxypyrene-1,3,6-trisulfonic acid as the indirect probe and achieved
      submicromolar (40-80 ppb) detection limits in a 2-min separation. The chemical
      warfare agent degradation products methylphosphonic acid, ethyl
      methylphosphonate, isopropyl methylphosphonate, and pinacolyl methylphosphonate
      were detected using the porphyrin tetrakis(4-sulfophenyl)porphine as the indirect
      probe and achieved detection limits of 0.1 microM (9 ppb), which are 1 order of
      magnitude better than that achieved using indirect UV detection. Baseline
      stability achieved with the violet diode laser was excellent, with dynamic
      reserve (DR) values of > 1000, which are 15 times better than that achieved using
      an unstabilized HeCd laser.

PMID- 11338596
TI  - Poly(ethylene-co-acrylic acid) stationary phases for the separation of shape
      constrained isomers.
AB  - A new approach for the synthesis of long alkyl chain length stationary phases for
      use in reversed-phase liquid chromatography is described. Poly(ethylene-co
      acrylic acid) copolymers (i.e., (-CH2CH2-)x[CH2CH(CO2H)-]y) with different levels
      of acrylic acid were covalently bonded to silica via glycidoxypropyl or
      aminopropyl linkages. 13C cross polarization magic angle spinning (CP/MAS)
      nuclear magnetic resonance (NMR) spectroscopy was used to characterize the new
      reversed-phase materials. Aspects of shape selectivity were evaluated for six
      different columns with Standard Reference Material (SRM) 869a, Column Selectivity
      Test Mixture for Liquid Chromatography. Selectivity for isomer separations was
      enhanced for stationary phases prepared with poly(ethylene-co-acrylic acid)
      containing a mass fraction of 5% acrylic acid. The relationship between alkyl
      conformation and chromatographic properties was studied by 13C magic angle
      spinning (MAS) NMR measurements, and correlations were made with the composition
      of the polymer. Finally, the effectiveness of this phase is demonstrated by the
      separation of several beta-carotene isomers.

PMID- 11338598
TI  - On-chip thermopneumatic pressure for discrete drop pumping.
AB  - A class of "lab-on-a-chip" devices use external air pressure for pumping discrete
      drops in a microchannel network. External air connectors can be cumbersome and
      are real-estate intensive. We have developed an on-chip technique to generate
      pressures required for metering and pumping of nanoliter-volume discrete drops.
      This is achieved by heating of trapped air in a pressure-generating chamber. The
      pressure-generating chamber is connected to the point of pressure application in
      the liquid-conveying microchannel through an air-delivery channel. The trapped
      air volume on the order of 100 nL is heated by resistive metal heaters by tens of
      degrees celcius to generate air pressures on the order of 7.5 kN/m2. The rate of
      discrete drop pumping is electronically controlled in the microchannel device by
      controlling the rate of air heating. Flow rates on the order of 20 nL/s are
      obtained in the microchannel (300 microns x 30 microns) by heating the air
      chamber at the rate of approximately 6 degrees C/s. In this paper, we describe
      the design, fabrication, and operation of this new technique of generating on
      chip air pressure, used for metering and pumping nanoliter discrete drops in
      microchannels.

PMID- 11338597
TI  - Separation of barbiturates and phenylthiohydantoin amino acids using the
      thermally tuned tandem column concept.
AB  - There are many more choices of column type than of eluent type for method
      development in reversed-phase liquid chromatography. It is common to switch
      between different column types or between the same type from different suppliers
      to achieve the desired separations. The key difficulty in modulating band spacing
      by adjusting the column type is that it is a discontinuous, "hit or miss"
      proposition. The thermally tuned tandem column (T3C) concept effectively solves
      this problem by connecting two columns in series and independently controlling
      the two column temperatures. The columns are chosen to have distinctively
      different chromatographic selectivities (band spacing), so that the unresolved
      peaks on one column are separated by the other. The optimized separation in the
      T3C is achieved by simultaneously tuning the two column temperatures. In this
      study, we used the T3C combination of a carbon and a conventional bonded phase
      for the separation of barbiturates and phenylthiohydantoin amino acids (PTH-amino
      acids). Good peak shapes and comparable retention times were observed on the two
      phases at room temperature. The selectivities on the two phases are quite
      different. Baseline separations were easily achieved with the T3C set although
      neither column could individually resolve all the peaks. We further compared the
      separation of barbiturates optimized by the T3C approach with that optimized by
      adjusting the mobile phase. We found that T3C gave a better separation. We
      believe that the T3C combination of a carbon phase and a bonded conventional
      reversed-phase material provides a powerful and general method to optimize the
      separation of various mixtures.

PMID- 11338599
TI  - Simultaneous electroanalysis of peroxyacetic acid and hydrogen peroxide.
AB  - The electrochemical behavior of peroxyacetic acid (PAA) in the presence of
      hydrogen peroxide (H2O2) has been investigated using cyclic voltammetry and
      hydrodynamic techniques [rotating disk electrode (RDE) voltammetry and rotating
      ring-disk electrode (RRDE) voltammetry]. The results have been analyzed aiming at
      simultaneous electroanalysis of both species. Glassy carbon and gold electrodes
      were used for this investigation. It was found that the reduction of PAA, as well
      as H2O2, is highly sensitive to the electrode material; for example, at 100 mV s
      1, the reduction peak potentials of PAA were 0.2 and -1.1 V at gold and glassy
      carbon electrodes, respectively. The well-separated steady-state limiting
      currents were obtained using a gold electrode for the reduction of both PAA and
      H2O2 and also a well-defined one for the oxidation of H2O2. On the basis of the
      RDE experiments, good calibration curves were obtained for both species over a
      wide range of their concentrations, for PAA and H2O2 in the range of 0.36 to 110
      and 0.11 to 34 mM, respectively. The simultaneous and selective electroanalysis
      of PAA and H2O2 in their coexistence is demonstrated for the first time.

PMID- 11338600
TI  - Monitoring motility, spreading, and mortality of adherent insect cells using an
      impedance sensor.
AB  - An emerging sensor technology referred to as electric cell-substrate impedance
      sensing (ECIS) has been extended for monitoring the behavior of insect cells
      including attachment, motility, and mortality. In ECIS, adherent cells were
      cultured on an array of eight small gold electrodes deposited on the bottom of
      tissue culture wells and immersed in a culture medium. Upon the attachment and
      spreading of cells on the gold electrode, the impedance increased because the
      cells acted as insulating particles to restrict the current flow. Experimental
      data revealed that insect cells interacted differently with various proteins used
      to precoat the gold electrode with concanavalin A as the best promoter to
      accelerate the rate of cell attachment. After the cells were fully spread, the
      measured impedance continued to fluctuate to reflect the constant motion and
      metabolic activity of the cells. As the cell behavior was sensitive to external
      chemicals, the applicability of ECIS for inhibition assays was demonstrated with
      HgCl2, trinitrotoluene, trinitrobenzene (TNB), and 2-amino-4,6-dinitrotoluene as
      model systems. Unlike conventional assays, the quantitative data obtained in this
      study are taken in real time and in a continuous fashion to depict cell motility
      and mortality.

PMID- 11338601
TI  - Ion-selective electrode for transmembrane pH difference measurements.
AB  - A triethylammonium-sensitive electrode was constructed using sodium tetrakis[3,5
      bis(2-methoxyhexafluoro-2-propyl)phenyl]borate as an ion-exchanger and benzyl 2
      nitrophenyl ether as a solvent mediator in a poly(vinylchloride) membrane matrix
      and was used to determine the pH difference across a cell membrane. The method is
      based on monitoring of the pH gradient-induced uptake of triethylammonium in
      situ. The triethylammonium electrode exhibited a near-Nernstian response to
      triethylammonium in the concentration range of 5 x 10(-6)-1 x 10(-2) M with a
      slope of 58.5 mV per concentration decade in a buffer solution composed of 150 mM
      NaCl and 10 mM NaH2PO4/Na2HPO4 (pH 7.5). The limit of detection was 1 microM. In
      experiments using liposomes, the uptake of triethylammonium into liposomes was
      quantitatively induced according to the pH difference across the liposomal
      membrane. The transmembrane pH differences in Escherichia coli cells and the
      light-induced pH differences across the envelope vesicles of Halobacterium
      halobium were successfully determined by the present method.

PMID- 11338602
TI  - Determination of properties of individual liposomes by capillary electrophoresis
      with postocolumn laser-induced fluorescence detection.
AB  - Individual liposome measurements by capillary electrophoresis with postcolumn
      laser-induced fluorescence detection facilitated the determination of liposome
      property distributions, two-dimensional plots, and an improved characterization
      of a liposomal preparation. This advancement in liposome analysis was feasible by
      using a high-sensitivity postcolumn laser-induced fluorescence detector wired for
      millisecond response. For each individual liposome containing fluorescein, peak
      height and migration time were determined. From these measurements the individual
      entrapped volumes and electrophoretic mobilities were determined. Distribution
      analysis of these properties facilitated comparison of various liposome dilutions
      and indicated that the method is reproducible and unaffected by the density of
      liposomes (10(7)-10(9) liposomes/mL) in the suspension. Furthermore, liposomes
      showed entrapped volumes that vary from 0.3 to 13 fL with apparent radius varying
      from 370 nm to 1.8 microns. Two-dimensional plots of reduced mobility versus
      kappa R (Debye parameter x liposome radius) revealed that the liposomes
      resuspended from a dried film of phospholipids are heterogeneous in regard to the
      surface charge density of individual liposomes. The described method has the
      potential of becoming a new tool for characterization of commercial liposomal
      preparations and theoretical studies.

PMID- 11338603
TI  - Determination of substrate and product concentrations in lactic acid bacterial
      fermentations by proton NMR using the ERETIC method.
AB  - A 1H NMR method is described for the determination of the concentration of a
      chemically diverse group of metabolites over a wide concentration range in
      fermentation medium. The method employs the use of the ERETIC signal, which
      produces a pseudo-FID acquired with the FID derived from the sample components.
      It is shown that this signal, once calibrated against an external standard
      solution, can be used to determine accurately the concentration of all components
      present in the medium. The method is rapid, reliable, and applicable to a wide
      range of biological fluids. Problems such as the invisibility of certain
      components in the spectrum are overcome by a simple regulation of the pH.

PMID- 11338605
TI  - Fluorescent cyclodextrin immobilized on a cellulose membrane as a chemosensor
      system for detecting molecules.
AB  - Dansyl glutamate-modified cyclodextrin (DnsGlu-beta-CD) was prepared as a
      fluorescent host, which is capable of being immobilized on a cellulose membrane
      (DnsGlu-beta-CD-membrane). The fluorescence intensity of DnsGlu-beta-CD decreased
      with increasing concentration of guest molecules, indicating that the host
      changes the location of the dansyl group from inside to outside the cyclodextrin
      cavity upon guest accommodation. Similar guest-induced decrease in the
      fluorescence intensity was observed for DnsGlu-beta-CD immobilized to a cellulose
      membrane. This result demonstrates that the cellulose membrane may be used as a
      practical supporting material of various chromophore-modified cyclodextrins and
      that DnsGlu-beta-CD-membrane is useful as a novel disposable chemosensor for
      molecules.

PMID- 11338606
TI  - Comparative studies on the certification of reference materials by ICPMS and TIMS
      using isotope dilution procedures.
AB  - A comparison of different isotope dilution mass spectrometric (IDMS) procedures
      using inductively coupled plasma mass spectrometry (ICPMS) and thermal ionization
      mass spectrometry (TIMS) was carried out to examine the degree of equivalence
      between the used procedures in terms of requirements for reference material
      certification. The comparison was based on the measurement results and their
      uncertainties. The sample used in this study is a pure zinc metal to be certified
      by the Bureau Communie de Reference (BCR) for amount contents of different trace
      elements. This study focuses on cadmium and thallium. The TIMS values contributed
      to the certified values. To guarantee identical conditions as far as possible for
      the procedures under investigation, the samples were split into subsamples after
      spiking and digestion took place. Thus, every IDMS procedure started with an
      identical set of samples. In total, four different IDMS procedures and one
      external calibration procedure using internal standardization as an example of
      routine analysis were applied. The IDMS procedures divide in a group with and a
      group without trace/matrix separation. Multicollector TIMS (TI-MC-MS) and
      multicollector ICPMS (ICP-MC-MS) were used in combination with trace/matrix
      separation, whereas quadrupole ICPMS (ICP-QMS) and ICP-MC-MS were also applied to
      nonseparated samples. All IDMS results agree well within their combined
      uncertainties, while some results from the external calibration procedure do not.
      IDMS results obtained by ICPMS without separation are comparable to those
      obtained by TI-MC-MS with separation regarding precision and accuracy. The
      smallest uncertainties were achieved using ICP-MC-MS in combination with
      trace/matrix separation.

PMID- 11338604
TI  - Synthesis of a terbium fluorescent chelate and its application to time-resolved
      fluoroimmunoassay.
AB  - A new nonadentate ligand, N, N, N1, N1-[2,6-bis(3'-aminomethyl-1'-pyrazolyl)-4
      phenylpyridine]tetrakis(acetic acid) (BPTA) for a Tb3+ fluorescent complex was
      synthesized. The Tb3+ complex is strongly fluorescent, having a large
      fluorescence quantum yield of 1.00 and very long fluorescence lifetime of 2.681
      ms in 0.05 M borate buffer of pH 9.1. Streptavidin (SA) was labeled with BPTA by
      using its succinimidyl monoester, and the BPTA-Tb(3+)-labeled SA was used in
      sandwich-type time-resolved fluoroimmunoassay (TR-FIA) of alpha-fetoprotein (AFP)
      and carcinoembryonic antigen (CEA) in human sera. The Tb(3+)-labeled SA was also
      used in competitive-type TR-FIA of bensulfuron-methyl (BSM) in water. The
      detection limits of these assays are 42 pg/mL for AFP, 70 pg/mL for CEA, and 0.4
      ng/mL for BSM. In addition, a new simultaneous measurement method for AFP and CEA
      in a human serum sample was developed by using 4,4'-bis(1",1",2",2",3",3" 
      heptafluoro-4",6"-hexanedion-6"-ly)chlorosulfo- o-terphenyl (BHHCT)-Eu(3+)
      labeled anti-AFP antibody, biotinylated anti-CEA antibody, and BPTA-Tb(3+)
      labeled SA. The concentrations of AFP and CEA in 39 human serum samples were
      determined, and the results were compared with those of the independently
      determined AFP and CEA by TR-FIA with a single-label method. A good correlation
      was obtained with the correlation coefficients of 0.991 for AFP and 0.994 for
      CEA.

PMID- 11338608
TI  - On-demand droplet spotter for preparing pico- to femtoliter droplets on surfaces.
AB  - A droplet spotter for on-demand generation of pico- to femtoliter droplets was
      developed to meet the requirement for high-density spotting of chemicals on a
      surface. Our droplet spotter involves applying a approximately 1000-V and
      approximately 10-ms pulse voltage to the tip of a capillary tube (o.d.
      approximately 18 microns; i.d. approximately 11 microns) supplied with water or a
      dye solution. The capability of the spotter was demonstrated by preparing a
      microarray of dye molecules. The microarray was prepared by spotting
      approximately 30-fL droplets of a dye solution on a surface at the density of one
      spot per 20 x 20 micron 2.

PMID- 11338607
TI  - One-step competitive immunoassay for cadmium ions: development and validation for
      environmental water samples.
AB  - A rapid, simple, and reliable competitive immunoassay was developed and validated
      for measurement of Cd(II) in environmental water samples. This assay employed a
      monoclonal antibody that recognizes Cd(II)-EDTA complexes as capture reagent and
      a Cd(II)-EDTA conjugate of horseradish peroxidase as an enzyme label. The assay
      depended on a competitive binding reaction between the enzyme conjugate and
      Cd(II)-EDTA complexes, derived from the environmental water sample, for the
      binding sites of the immobilized antibody. The concentration of Cd(II) in the
      sample was quantified by the ability of its EDTA complexes to inhibit the binding
      of the enzyme conjugate to the antibody and, subsequently, color formation in the
      assay. The assay was specific to Cd(II), with a limit of detection of 0.3 ppb.
      Ca(II), Mg(II), and Fe(III), the metal ions commonly found in ambient water at
      relatively high concentrations, did not interfere with the assay. Mean analytical
      recovery of added Cd(II) was 100.29 +/- 3.60. The precision of the assay was
      satisfactory; coefficients of variation were 3.6-10.9 and 4.81-10.21% for intra-
      and interassay precision, respectively. The assay compared favorably with
      graphite furnace atomic absorption spectroscopy in its ability to accurately
      measure Cd(II) spiked into water samples from a Louisiana bayou.

PMID- 11338609
TI  - An immunoassay for Leu-enkephalin based on a C-terminal aequorin-peptide fusion.
AB  - Recently we demonstrated that the fusion of an octapeptide to the C-terminus of a
      cysteine-free mutant of aequorin showed no inhibitory effect on the luminescence
      activity of the photoprotein. This observation is of particular importance when
      the use of aequorin as a label in the development of immunoassays for peptides
      whose activity lies in their C-terminal region or the epitope for antibody
      recognition is at their C-terminus is desired. In the case of opioid peptides,
      antibodies are directed toward their C-terminus as they differ from each other at
      this terminus. The goal of this study was to develop an immunoassay for Leu
      enkephalin, a mammalian opioid peptide, using a C-terminal aequorin-peptide
      fusion protein. For that, the N-terminus of Leu-enkephalin was genetically fused
      to the C-terminus of a cysteine-free mutant of aequorin. It was observed that the
      C-terminal conjugated aequorin maintained its luminescence activity. An
      immunoassay for Leu-enkephalin was then developed using the aequorin-Leu
      enkephalin fusion protein as a labeled analyte in a competitive as well as in a
      sequential binding mode. It was demonstrated that aequorin can be used as a label
      in peptide assays in which it is critical that the peptide's C-terminus be free
      for activity and/or for antibody recognition.

PMID- 11338610
TI  - Elimination of high-voltage field effects in end column electrochemical detection
      in capillary electrophoresis by use of on-chip microband electrodes.
AB  - The influence of the separation voltage on end column electrochemical detection
      (EC) in capillary electrophoresis (CE) has been investigated using an
      electrochemical detector chip based on an array of microband electrodes. It is
      shown, both theoretically and experimentally, that the effect of the CE electric
      field on the detection can be practically eliminated, without using a decoupler,
      by positioning the reference electrode sufficiently close to the working
      electrode. In the present study, this was demonstrated by using an experimental
      setup in which neighboring microband electrodes on a chip, positioned 30 microns
      from the end of the CE capillary, were used as working and reference electrodes,
      respectively. The short distance (i.e., 10 microns) between the working and
      reference electrode ensured that both of the electrodes were very similarly
      affected by the presence of the CE electric field. With this experimental setup,
      no significant influence of the CE voltage on the peak potentials for gold oxide
      reduction could be seen for CE voltages up to +30 kV. The detector noise level
      was also found to be reduced.

PMID- 11338611
TI  - IMPACT: revitalizing TMA's political clout.

PMID- 11338612
TI  - The untapped potential of electronic medical records. Pt. 2--Solving the problems
      of EMR technology.

PMID- 11338613
TI  - Patient and physician: both losers.

PMID- 11338615
TI  - Atypical eclampsia: a case report and review.
AB  - Up to one-third of cases of eclampsia occur in the postpartum period. Often there
      is evidence of preeclampsia, which alerts the physician to be prepared for the
      possibility of seizures. Eclampsia is an obstetrical emergency often requiring
      intensive care and monitoring. This reports the case of a 33-year-old gravida 5
      para 4 abortus 1 who presented ten days postpartum with eclampsia. The patient
      had no history of hypertension, edema, or proteinuria during her prenatal visits
      or hospitalization, and has no history of preeclampsia or eclampsia in previous
      pregnancies. This case illustrates the rare occurrence of eclampsia late in the
      postpartum period and the equally rare onset of eclampsia without prior evidence
      of preeclampsia during her pregnancy. It is followed by a brief review of the
      relevant literature.

PMID- 11338614
TI  - Tinsley Harrison--a personal account.

PMID- 11338617
TI  - [BSE: clinical diagnosis and field experience].
AB  - The clinical diagnosis 'suspected of having BSE' is difficult. Cows older than
      2.5 years, presented to the private veterinary practitioner with disturbed
      locomotion present for more than 14 days and with no detectable cause, should be
      investigated with suspicion. Questions on changes in behaviour of the animal and
      during the examination attention on exaggerated responses to handling and sound
      can give additional information. Notification of suspected cases and gained field
      experiences are discussed.

PMID- 11338616
TI  - Working toward a comprehensive school health model in Tennessee schools.

PMID- 11338620
TI  - [Veterinary drugs, for many a worry].

PMID- 11338619
TI  - [Transmission of the foot and mouth disease virus through milk and meat products
      is not a threat for human health].

PMID- 11338618
TI  - [The clinical symptoms of foot and mouth disease in the first confirmed cases at
      five different farms in the Netherlands].

PMID- 11338621
TI  - [Who is the bitten dog? Legal liability of damage by animals].

PMID- 11338622
TI  - [BSE and pet food: is animal feed safe?].

PMID- 11338625
TI  - [Foot and mouth disease].

PMID- 11338624
TI  - [Discussion of fetus delivery method].

PMID- 11338626
TI  - [Foot and mouth disease outbreak forces to reconsider].

PMID- 11338623
TI  - [CAVP processed 3 complaints in 2000].

PMID- 11338627
TI  - [Recognition of cattle veterinarians: what should we do with it??].

PMID- 11338628
TI  - Are we getting smarter?

PMID- 11338629
TI  - Nourishing your brain.

PMID- 11338630
TI  - Prescription drugs at bargain prices.

PMID- 11338631
TI  - Leg waxing and life everlasting.

PMID- 11338633
TI  - [New drug for irritable bowel syndrome].

PMID- 11338632
TI  - [Evidence-based = evidence proved?].

PMID- 11338634
TI  - [Pharmacotherapy of bronchial asthma].

PMID- 11338635
TI  - [Nasal polyps. Diagnosis and therapy].

PMID- 11338636
TI  - [Abdominal typhus and paratyphoid fever].

PMID- 11338639
TI  - Endoscopic view of the basal lamella.

PMID- 11338638
TI  - Exostoses of the external auditory canal.

PMID- 11338637
TI  - [Heartburn in pregnancy?].

PMID- 11338640
TI  - Papillomata masquerading as vocal fold nodules.

PMID- 11338641
TI  - Congenital sensorineural hearing loss: Mondini's deformity.

PMID- 11338642
TI  - A patient with central dysrhythmia, reduced vestibular response, and directional
      preponderance.

PMID- 11338643
TI  - Incidental petrous apex findings on magnetic resonance imaging.
AB  - We performed a retrospective chart review to categorize a group of petrous apex
      findings that were noted incidentally on magnetic resonance imaging (MRI) in 88
      patients. These patients were among those who had been seen at a tertiary care
      center between July 1988 and July 1998. These incidental findings, which were
      unrelated to the presenting clinical manifestations, included asymmetric fatty
      bone marrow (n = 41), inflammation (19), cholesterol granulomas (14),
      cholesteatomas (9), and neoplasms (5). Followup imaging and clinical surveillance
      of these patients has not demonstrated any significant change in the incidentally
      detected lesions. In all cases, the incidental MRI findings represented benign
      pathology.

PMID- 11338644
TI  - Lingual artery embolization for severe and uncontrollable postoperative tonsillar
      bleeding.
AB  - We performed emergent angiography of the external carotid artery to evaluate a
      patient who experienced uncontrollable oropharyngeal bleeding 3 days following an
      adenotonsillectomy. Angiography demonstrated a left lingual artery disruption and
      hemorrhage. We then performed a coil embolization of the left lingual artery,
      which immediately halted the hemorrhage. We conclude that coil embolization is a
      rapid and effective strategy for the management of massive, uncontrollable
      postoperative tonsillar bleeding.

PMID- 11338645
TI  - Bilateral submandibular gland infection presenting as Ludwig's angina: first
      report of a case.
AB  - We diagnosed and treated a case of Ludwig's angina in a 45-year-old man who had
      edema of the floor of mouth and the tongue along with bilateral submandibular
      sialadenitis and sialolithiasis. We secured the patient's airway via nasal
      fiberoptic intubation in the surgical intensive care unit and administered
      intravenous antibiotics. The edema subsided, and the patient was extubated on the
      third postoperative day and discharged shortly thereafter. To our knowledge, this
      is the first reported case of a patient with bilateral submandibular sialadenitis
      and sialolithiasis presenting as Ludwig's angina. Despite the decreasing
      incidence of this disease, Ludwig's angina remains an important disease process
      because a failure to control the airway can have disastrous consequences. Proper
      diagnosis, airway control, antibiotic therapy, and occasionally surgical
      management are essential to ensure the safety of the patient.

PMID- 11338646
TI  - Head and neck granulocytic sarcoma with acute myeloid leukemia: three rare cases.
AB  - We conducted a retrospective review of pathology files and hospital records and
      identified three unusual presentations of granulocytic sarcoma associated with
      acute myeloid leukemia (AML) of the head and neck. At least one mass was observed
      on the skin of all three patients. A 17-year-old boy had masses in each temporal
      region that were accompanied by bilateral facial paralysis. He was administered
      chemotherapy and radiotherapy, but he died of infection secondary to a second
      relapse 29 months after the initial diagnosis. A 17-year-old girl had a tumor in
      the right parotid area. She received chemotherapy, but she died of infection and
      bleeding 2 months after the initial diagnosis. A 33-year-old man had numerous
      tumors widely disseminated over his skin. He received chemotherapy and was in
      remission 12 months after the initial diagnosis, but he eventually relapsed and
      died. Granulocytic sarcoma can be localized in unexpected regions, including the
      head and neck. This tumor is very often misdiagnosed as a malignant lymphoma,
      which leads to delayed treatment and a poor outcome. Therefore, clinical and
      histopathologic findings should be evaluated before any diagnosis of malignant
      lymphoma is pronounced. Immunohistochemical stains should also be performed on
      patients with suspected granulocytic sarcoma, and aggressive chemotherapy or
      immunotherapy should be administered. We believe that high-dose chemotherapy can
      improve survival rates in granulocytic sarcoma associated with AML.

PMID- 11338647
TI  - Endoscopic sinus surgery for the treatment of chronic sinusitis in geriatric
      patients.
AB  - Although endoscopic sinus surgery is a well-documented procedure for the
      treatment of chronic sinusitis in children and adults, no study has been
      conducted to specifically investigate its application in a geriatric population.
      We undertook to fill this void by analyzing the records of 1,112 patients who had
      undergone endoscopic sinus surgery for chronic sinusitis in our department
      between April 1988 and March 1998. We categorized these patients by age. There
      were 171 patients (15.4%) in the geriatric group (age: > or = 65 yr), 837
      patients (75.3%) in the adult group (age: 17 to 64), and 104 patients (9.4%) in
      the pediatric group (age: < or = 16 yr). We found that the geriatric group
      experienced a disproportionately larger share of operative complications, but
      most of them were minor. Outcomes were similar in all three groups. We conclude
      that endoscopic sinus surgery is a safe and effective treatment for older
      patients with chronic sinusitis.

PMID- 11338648
TI  - Reinforcement of an end-to-end tracheal resection anastomosis with fibrin glue: a
      case report.
AB  - Tracheal resection and primary anastomosis is the treatment of choice for a short
      segment stenosis. However, the procedure does carry the risk of two potentially
      fatal complications: anastomosis breakdown and leak. We describe the case of a 67
      year-old man who was treated for a 3-cm tracheal stenosis secondary to a
      prolonged intubation and multiple tracheostomies. The patient underwent a
      tracheal resection and primary anastomosis. The anastomosis was reinforced with
      fibrin sealant, which created an airtight seal. The patient was extubated
      postoperatively, and he healed without complication. Fibrin sealant is a
      convenient, safe, and effective material for reinforcing anastomotic suture
      lines.

PMID- 11338649
TI  - Recurrent glomus tumor of the pinna: report of a case.
AB  - We describe a rare case of a glomus tumor of the pinna. The lesion produced a
      brief but sharp pain that occurred spontaneously, intermittently, and upon
      tactile stimulation. Surgical excision with wide margins was successful. We
      believe this to be only the third case of a glomus tumor of the auricle that has
      been reported in the literature.

PMID- 11338650
TI  - Spindle cell lipoma of the parapharyngeal space: first report of a case.
AB  - Spindle cell lipomas are usually located in the subcutaneous tissue of the back,
      shoulders, and neck. To our knowledge, the presence of such a tumor in the
      parapharyngeal space has not yet been described. We evaluated a 45-year-old man
      with a tender swelling of the right parotid area that had reached the
      submandibular area. Clinical examination and magnetic resonance imaging revealed
      the presence of a tumor that coated the parotid area laterally and extended into
      the center of the parapharyngeal space, thus causing a dislocation of the
      pharyngeal muscles and mucosa. We performed a total parotidectomy and
      submandibulectomy on the right side and extirpated the parapharyngeal tumor. We
      were able to spare the facial nerve, and no facial paralysis occurred. Histologic
      examination revealed an atypical lipomatous tumor with a remarkably large portion
      of spindles.

PMID- 11338651
TI  - Cortical representation of the vestibular system as evidenced by brain electrical
      activity mapping of vestibular late evoked potentials.
AB  - We examined the space and temporal distributions of the rotatory evoked brain
      electrical activity patterns (brain electrical activity mapping of vestibular
      evoked potentials [VestEP]) in humans. We performed a longitudinal scalp line
      analysis, transversal line analysis, and clockwise/counterclockwise rotation
      analysis of the VestEP principal components in 75 healthy persons aged 22 to 30
      years (mean: 25.8). We found that the shortest VestEP latencies and the highest
      amplitudes were registered in a relatively distinct cortical area that is covered
      by the transversal electrode line T3-C3-Cz-C4-T4, in accordance with the 10/20
      international electrode scheme. This area corresponds to the posterior part of
      the frontal lobe (Brodmann's area 4, the primary motor field of the isocortex)
      and the anterior parts of the cerebral parietal lobe (the gyrus postcentralis,
      which corresponds to the primary somatosensory fields, Brodmann's areas 1, 2, and
      3). In this article, we discuss a method of investigation that exhibits the
      VestEPs, and we review one normal case and three typical cases of pathologic
      VestEPs.

PMID- 11338652
TI  - Psychiatric manifestations of medications commonly prescribed in otolaryngology.
AB  - Otolaryngologists, nurses, and psychological professionals should be familiar
      with the potential psychiatric side effects of medications that are commonly
      prescribed by otolaryngologists. Because some of these side effects are atypical,
      their relationship to medications might not be obvious. An awareness of the
      potential for psychiatric side effects caused by adrenocorticoids, antihistamines
      and decongestants, and antisecretory medications will help the clinician avoid or
      detect and treat drug-induced disorders, as will an awareness of the potential
      for side effects caused by combinations of medications. Identification of
      individual risk factors such as age, pre-existing organic brain disease, a
      history of drug abuse or dependence, or coexisting or pre-existing psychiatric
      disorders is important in preventing and detecting drug-induced psychiatric
      disorders. The drugs discussed in this article can have serious, even fatal,
      interactions with certain psychiatric medications.

PMID- 11338653
TI  - Malignant tumors of the nose and paranasal sinuses: a retrospective review of 291
      cases.
AB  - Malignant neoplasms of the nose and paranasal sinuses are not common among the
      general population. We present a retrospective study of 291 cases of malignant
      tumors of the nose and paranasal sinuses that were diagnosed in a northern
      Romanian population over a period of 35 years. We review the etiology, diagnosis,
      prognosis, and treatment of these tumors.

PMID- 11338654
TI  - Stool cultures for acute flaccid paralysis surveillance.

PMID- 11338655
TI  - International Network of Paediatric Surveillance Units.

PMID- 11338656
TI  - Does measles-mumps-rubella (MMR) vaccination cause inflammatory bowel disease and
      autism?

PMID- 11338657
TI  - [Strength training with superimposed vibrations].
AB  - To examine the effects of strength training with superimposed vibrations ten
      subjects trained over a period of six weeks (three sessions per week) one leg
      with back squats and superimposed vibrations and the other leg with traditional
      squats. In each training session participants performed 4 sets with 8-12
      repetitions. Before and after the training period maximum strength and rate of
      force development were measured. The results show that both training modes
      induced comparable and statistical significant increases in maximum strength
      (vibration training +6.5%, traditional training +6.2%. The slight increases in
      rate of force development in both groups didn't reach statistical significance.
      As a consequence it seems that strength training with superimposed vibrations for
      the leg extensor chain is not superior to a traditional training mode.

PMID- 11338658
TI  - [Orthopedic problems in older marathon runners].
AB  - 58 marathon runners with an age average of 44.5 years were examined 6 months
      before the marathon in Berlin orthopedically. The orthopedic examination shows
      spinal column faulty burdens, muscular dysbalances as well as overload damages in
      the area of the knee joints and the achilles tendons. 42 probationers began after
      a biannual training with the marathon, one had to give up. Occurred during the
      marathon-training with 27 of the probationers orthopedic problems, especially in
      the area of the knee joint and the area of the achilles tendon. During the
      marathon 18 of the participants finished with orthopadic troubles. The
      examination shows, which orthopedic troubles with older marathon runners appears.
      Beside a sport medical suitability examination, a premature aimed therapy is
      necessary with the appearance of troubles since normally chronic overload damages
      and joint-wear threaten. When keeping the corresponding handicaps, a long-time
      marathon-training is possible also in the higher age without health risks for
      overuse injuries.

PMID- 11338659
TI  - [Effects of knee braces on sensorimotor capabilities of patients with ACL
      reconstruction].
AB  - In 25 test persons with Anterior-Cruciate-Ligament (ACL)-Operation the
      sensomotory capabilities of the affected and the unaffected side were examined by
      KAT 2000 (BREG Inc., Vista, C.A., USA) with and without knee-brace (Hypex knee
      brace/Fa. Aircast-Europa GmbH). The results were compared with those of a control
      group. In all cases of test variations (both leg-static/both leg-dynamic/one leg
      static) there were significant differences between testing with and without knee
      brace. In the one leg-static test there was an improvement of 30% (p < 0.01), in
      the both leg-static test an improvement of 24% (p < 0.01). The both leg-dynamic
      showed a similar result (23.8%; p < 0.01). These noticed adaptations may be
      mediated by improvements of proprioceptive and exteroceptive capabilities and a
      positive impact on the anticipative control of behavior. The results of the
      control group differ in only a few cases from the results in the group of
      patients. This may be judged as indicator for the variety of sensomotory
      capabilities in the general population.

PMID- 11338660
TI  - [Effects of low-frequency pulsed electromagnetic fields on the proliferation of
      chondrocytes].
AB  - Chondrocytes isolated from the human cartilage of 5 patients between the ages 23
      and 56 were exposed to low frequency pulsed electromagnetic fields (9 mT; 3 Hz)
      for a daily period of 60 minutes on 5 consecutive days and then every 48 hours
      for the next 6 days (11 days in total). Cell viability was estimated using trypan
      blue exclusion and proliferation was estimated by counting the cells in a
      haemacytometer. Cell morphology was compared for control purposes by directly
      observing the cells under a light microscope after staining cells in a
      haematoxylin and eosin solution. The results were statistically analysed and
      compared to a control sample. Data revealed that exposing cells isolated from
      human cartilage to pulsed electromagnetic fields (9 mT; 3 Hz) led to a
      significantly higher number of cells in comparison to the control sample. Among
      the cells from the 5 patients, growth varied between 1.1 to 3.0 folds compared to
      the control sample. The difference in cell viability between the exposed cells
      and the control sample was, however, not significant. Some morphological
      variations were revealed when the cells were observed under a light microscope.
      The exposed cells were thinner and longer than the control cells which were large
      and flat. The exposed cells tended to grow in a more uniform direction while the
      control cells grew in all directions. These differences in morphology and growth
      may be related to the higher density of the exposed cells.

PMID- 11338661
TI  - [Bicycle accidents in the aged].
AB  - Between January 1st, 1998 and May 31st, 2000 the total of 7852 patients were
      treated at the Klinik Lindenplatz. 36 of them (14 male and 22 female) received an
      orthopedic rehabilitation after an operative treatment of a fracture due to a
      bicycle accident. 57% of them were older than 60. In 81% of the injuries the
      lower extremities were affected. Main injuries were medial fractures of the neck
      of the femur and fractures of the proximal femur. Skidding bikes had most
      frequently caused the accidents (44%). With the elderly patients one of the
      common causes of an injury was their falling from the bike or their failing
      attempt of getting on or off. Most of the patients had fallen without hitting or
      colliding with another biker, car or other extraneous influence. As the most
      serious fractures have occurred to elderly people, it is worth discussing the use
      of a hip protector, which could avoid these severe injuries.

PMID- 11338662
TI  - [The end-grade stretching behavior of ventral collagenous connective tissue
      structures of the foot during a passively-induced movement in the plantar flexion
      as an "in vivo study"].

PMID- 11338663
TI  - Chemistry of uncondensed 1,2,4-triazines, Part IV. Synthesis and chemistry of
      bioactive 3-amino-1,2,4-triazines and related compounds--an overview.
AB  - Studies on the chemical reactivity of bioactive 3-amino-1,2,4-triazines are
      reviewed. The synthesis, unique features and pharmacological significance of
      these constituents are discussed.

PMID- 11338664
TI  - Substituted phenoxyalkylpiperazines as dopamine D3 receptor ligands.
AB  - A novel series of potential antipsychotic agents were prepared by combination of
      condensed heterocycles containing bridgehead nitrogen with (2
      methoxyphenyl)piperazine using phenoxyalkyl spacer of variable length. The
      affinity of the compounds was determined at rat cloned D3 and rat D2, 5-HT1A
      receptors by an vitro receptor binding assay. The D3 selectivity of the compounds
      was calculated from the Ki values.

PMID- 11338665
TI  - Decreased cytotoxicity and increased antimitotic activity of a proline analogue
      of chlorambucil as a prodrug susceptible to the action of fibroblast's prolidase.
AB  - We synthesized an proline analogue of chlorambucil (CH-pro) as a prodrug
      susceptible to the action of ubiquitously distributed, cytosolic imidopeptidase-
      prolidase [E.C.3.4.13.9]. A conjugation of chlorambucil (CH) with proline through
      an imido-bond resulted in the formation of a good substrate for prolidase. We
      have compared several aspects of biological actions of CH and its prodrug in
      cultured normal human skin fibroblasts. The prodrug was found to be more
      effectively transported into the cells than the free drug. Moreover, in
      opposition to CH, CH-pro had no inhibitory effect on fibroblast's prolidase
      activity against the endogenous substrate, glycyl-L-proline. Lower cytotoxicity
      and a higher antimitotic activity of the prodrug, compared to the free drug, was
      observed. CH and CH-pro at concentrations of 25 microM led to a 30% and 10%,
      decrease in cell viability in confluent human skin fibroblasts. IC50 values of CH
      and CH-pro for DNA synthesis was found to be 30 microM and 7 microM, suggesting
      higher antimitotic potency of the pro-drug compared to the free drug. CH-pro also
      evoked lower ability to inhibit collagen biosynthesis in cultured fibroblasts
      than the free drug. IC50 values of CH and CH-pro for collagen biosynthesis were
      found at about 15 microM and 30 microM, respectively. Targeting of prolidase as a
      prodrug-converting enzyme may serve as a novel strategy in pharmacotherapy of
      various diseases, leading to the increase in therapeutic efficacy and reduction
      in untoward side effects of antineoplastic agents.

PMID- 11338666
TI  - Synthesis and biochemical evaluation of some novel N-acyl phosphono- and
      phosphinoalanine derivatives as potential inhibitors of the D-glutamic acid
      adding enzyme.
AB  - A series of N-(5-phthalimidopentanoyl)-, N-[2-(2-ethoxy)acetyl]-, and N-(7
      oxooctanoyl)-phosphono and phosphinoalanine derivatives has been synthesized and
      evaluated for inhibition of the D-glutamic acid-adding enzyme (MurD) of
      peptidoglycan biosynthesis.

PMID- 11338667
TI  - 4-aryl-6,6-dimethyl-1,2,3,4,5,6,7,8-octahydroquinazoline-2,5-diones: synthesis,
      chromatographic resolution and pharmacological activity.
AB  - In this study, a series of 4-aryl-6,6-dimethyl-1,2,3,4,5,6,7,8-
      octahydroquinazoline-2,5-diones were synthesized by condensing urea with 4,4
      dimethyl-1,3-cyclohexanedione and appropriate aromatic aldehydes according to the
      Biginelli reaction. The structures of the compounds were characterized by
      spectroscopic methods. The racemic compounds were resolved into the enantiomers
      by HPLC on amylose tris(3,5-dimethylphenylcarbamate) (Chiralpak AD). The
      compounds were tested in vitro for their calcium antagonistic activities. BaCl2
      induced contractions of rat ileum were inhibited dose-dependently. Compounds 3
      and 5 exerted weak calcium antagonistic activity on smooth muscles compared with
      the standard, nicardipine.

PMID- 11338668
TI  - [Unexpected formation of spiro(benzofuran-2,2'-(1,4)benzothiazines) from
      aurones].
AB  - The reaction between (Z)-2-benzylidene-3-coumaranones (aurones) 4B, 2
      aminothiophenol and sodium ethanolate does not give the expected benzofuro[2,3
      c][1,5]benzothiazepines 7, but yields the spiro compounds 8. Their structures are
      confirmed by an X-ray analysis.

PMID- 11338669
TI  - Separation, analyses and syntheses of trimethoprim impurities.
AB  - The analysis of several impurities of the chemotherapeutic agent trimethoprim
      with various methods, including thin layer chromatography, gas chromatography,
      capillary electrophoresis as well as nuclear magnetic resonance is described.
      These methods were used to identify new impurities in trimethoprim batches. The
      main impurities were separated by column chromatography. To ensure the identity
      of the impurities, de novo syntheses were successfully carried out. With the
      methods described, it was possible to detect, separate and identify new
      impurities in trimethoprim batches.

PMID- 11338670
TI  - Stability of fluoxetine in stored plasma, aqueous, and methanolic solutions
      determined by HPLC with UV detection.
AB  - The stability of fluoxetine was studied in plasma, and in aqueous and methanolic
      solutions at a concentration of 6 micrograms/ml under different storage
      temperatures and time intervals up to three months. Fluoxetine exhibited good
      stability at -20 and 5 degrees C, but was unstable at room temperature under the
      same conditions. A significant loss was observed at the second, third and fifth
      weeks in plasma, aqueous solution and methanolic solution respectively (P >
      0.95). At the end of the experiment, the amount of fluoxetine-recovered was at
      least 55.25% regardless of the storage conditions. Chromatography was performed
      using a C8 column and the mobile phase consisted of
      methanol/acetonitrile/triethylamine solution (35:20:45) adjusted to pH 5.5. UV
      detection was at 230 nm. Fluoxetine was isolated from plasma by liquid-liquid
      extraction (LLE) with dichloromethane as extracting solvent after addition of 20%
      ammonia solution. The standard curve was linear over the range of 0.05-10
      micrograms/ml. The inter-day coefficient of variation and the lower detectable
      limit were 6.92% and 0.05 microgram/ml respectively.

PMID- 11338671
TI  - Direct enantiomeric purity determination of the chiral anesthetic drug
      bupivacaine by 1H NMR spectroscopy.
AB  - The direct determination of the enantiomeric purity of the chiral anaesthetic
      drug bupivacaine has been developed using 1H NMR (400 MHz) spectroscopy with a
      chiral solvating agent. Optimization of experimental conditions in terms of
      temperature, substrate concentration and solvating agent to substrate molar ratio
      provided two significant signal splittings for chiral recognition resulting from
      diastereomeric solvation. Based on the relative intensities of the aliphatic
      methyl resonances assigned to (S)-(-)- and ($)-(+)-bupivacaine, the analysis of
      synthetic mixtures of the enantiomers by the proposed NMR method resulted in
      assay values which agreed closely with the known quantities of each enantiomer in
      the mixtures tested. The mean +/- SD recovery values for the (R)-(+)-enantiomer
      was 100.0 +/- 0.6% of added antipode (n = 7). The optically pure enantiomers were
      used to establish the minimum sensitivity of the NMR spectroscopic method of
      chiral analysis.

PMID- 11338672
TI  - Determination of bronopol in cosmetic products by HPLC with electrochemical
      detection.
AB  - A procedure is described for the assay of bronopol in cosmetics by HPLC coupled
      with constant-potential amperometric detection. Samples were analysed on an
      Alltima C18 column with methanol-phosphate buffer as the eluent and detected at a
      porous graphite electrode set at a reduction potential of -0.9 V. The recovery of
      bronopol from different cosmetic matrices was between 96.4 and 98.8% and the
      precision of the method was better than 4.5% relative standard deviation.

PMID- 11338673
TI  - Naproxen-Eudragit microspheres: screening of process and formulation variables
      for the preparation of extended release tablets.
AB  - The objectives of the present study were to screen the formulation and process
      variables for the preparation of extended release naproxen tablets with Eudragit
      L100-55. The tablets were prepared by compression of microspheres that were
      obtained by a coprecipitation technique. The process involved dissolution of
      naproxen and Eudragit L 100-55 in alcohol USP followed by the addition of an
      aqueous solution containing a surfactant and deaggregating agents. The mixture
      was stirred for a specified time period to obtain microspheres, which were
      filtered and air-dried to a constant weight. The microspheres were then
      compressed to obtain plain tablets with a diameter of 12 mm. A 7-factor 12-run
      Plackett-Burman screening design was employed to evaluate the main effects of
      homogenization time (X1), rate of water addition (X2), amount of polymer (X3),
      amount of precipitating solution (X4), concentration of electrolytes (X5),
      compression pressure (X6), and the concentration of lubricant (X7) on the rate of
      drug release. The response variable was cumulative percent of naproxen dissolved
      in 12 h in simulated intestinal fluid with constraints on responses that included
      percent yield, hardness, thickness, and the angle of repose. Mathematical
      relationship for percent of naproxen dissolved in 12 h (Y5) with various factors
      yielded the following polynomial equation; Y5 (% dissolved in 12 h) = 95.48 +
      0.53 X1 + 3.51 X2 + 3.84 X3 - 3.80 X4 - 2.46 X5 - 2.90 X6 - 3.91 X7. The results
      showed that all the seven factors affected, with varying order, the release of
      naproxen from its compressed tablets.

PMID- 11338674
TI  - Non-protein bound dienogest in serum and salivary dienogest in women taking the
      oral contraceptives Certostat and Valette.
AB  - Dienogest (17 alpha-cyanomethyl-17-hydroxy-4,9-estradien-3-one) is the
      progestagen component of the oral contraceptives Certostat and Valette. In
      contrast to other 19-norsteroid progestagens like levonorgestrel, norethisterone,
      gestodene and 3-ketodesogestrel, dienogest does not bind to sexual hormone
      binding globulin (SHBG). The absent binding to SHBG results in a high portion of
      free, non-protein bound dienogest in serum. In female volunteers taking the oral
      contraceptives Certostat and Trisiston, the part of non-protein bound dienogest
      and levonorgestrel, respectively, in serum was determined by the method of
      centrifugal ultrafiltration. The portion of free dienogest was found to be 9.55
      +/- 0.95% (m +/- SD, n = 13) of total serum dienogest. Free levonorgestrel
      constituted 0.97 +/- 0.14% (n = 12) of total serum levonorgestrel. In an
      investigation with 47 female volunteers taking Certostat, serum total dienogest
      was quantified by a specific radioimmunoassay and free dienogest in serum by
      centrifugal ultrafiltration. In the serum samples with dienogest concentrations
      in the range of 4.1-57.7 ng/ml, the part of free, non-protein bound dienogest was
      found to be 8.90 +/- 0.54% of serum total dienogest. There is a high correlation
      between serum total dienogest and free dienogest (r = 0.989). In another
      investigation with 20 female volunteers taking the contraceptive Valette, serum
      total dienogest and salivary dienogest were quantified by radioimmunoassay and
      free dienogest in serum by centrifugal ultrafiltration. In the serum samples with
      dienogest concentrations in the range of 7.5-50.6 ng/ml, the part of free, non
      protein bound dienogest was 8.78 +/- 0.77% of serum total dienogest. Salivary
      dienogest constituted 7.99 +/- 0.94% of serum total dienogest showing a high
      correlation with serum free dienogest (r = 0.953) and serum total dienogest (r =
      0.958). The high portion of non-protein bound compound in serum is a
      characteristic pharmacokinetic feature of dienogest.

PMID- 11338675
TI  - Cytochrome P450 1A1 and 4A activities in isolated rat spleen lymphocytes.
AB  - In this study the activity of Cytochrome P 450 (CYP) enzymes in isolated spleen
      lymphocytes of Wistar rats was estimated. 7-Ethoxyresorufin-O-deethylase was
      analysed to determine the activity of CYP 1A1/2. The activity was increased 2.2
      fold by pretreating the animals with 3-methylcholanthrene, and 1.3-fold after the
      addition of the mitogen concanavalin A to the lymphocyte culture. Pretreatment of
      the rats with phenobarbitone did not enhance the basal enzyme activity. To
      estimate reductive activities the azoreduction of 4-(N,N-dimethyl
      amino)azobenzene was analysed. Again detectable turnovers were found which could
      be increased 4-fold after the addition of concanavalin A. Azo-reductase activity
      could also be increased 2-fold after clofibrate was added to the lymphocyte
      cultures, and was decreased by adding metyrapone so that it was concluded that
      azoreduction may be partly due to the CYP 4A-family.

PMID- 11338676
TI  - The influence of acetoacetate and butyrate on calcium influx and ATP
      concentrations in HT-29 cells.
AB  - The effects of acetoacetate and butyrate on Ca(2+)-influx in HT-29 cells were
      unknown. Extracellular signals can be transferred to the intracellular
      environment of the cell via changes in the Ca(2+)-concentration. Extracellular
      Ca2+ may enter the cell via Ca(2+)-channels in the plasma membrane. Physiological
      processes occurring within the cell are dependent on Ca(2+)-concentration,
      including enzyme activity. Intracellular Ca(2+)-concentrations were measured
      using Fura-2/AM, a fluorescent intracellular Ca(2+)-probe. Ca(2+)-concentrations
      were measured immediately on application of the inducers to the cells, as well as
      after a 9 day incubation period. The effect of these inducers on the L-type
      voltage-operated Ca(2+)-channels were determined using the whole-cell patch-clamp
      technique. To validate these results for the intestinal epithelial model,
      membrane current studies were performed on HT-29 cells grown on a polycarbonate
      membrane. ATP concentrations were measured, and the theoretical effect of the
      inducers on PDE 4 activity was determined. It was found that both acetoacetate
      and butyrate blocked Ca(2+)-influx through the L-type voltage-operated Ca(2+)
      channels, resulting in the initial low Ca(2+)-concentration (p < 0.05). The
      blockage effect is short-lived as after a 9 day incubation period in the presence
      of the inducers, Ca(2+)-concentrations were higher than that of the HT-29 control
      sample (p < 0.05). ATP concentrations of the cells were decreased in the presence
      of the inducers (p < 0.05), whilst it was suggested that no interaction between
      the catalytic site of PDE 4 and the inducers existed.

PMID- 11338677
TI  - Compound mixtures in Caco-2 cell permeability screens as a means to increase
      screening capacity.
AB  - The purpose of this investigation was a study of simultaneous permeability
      measurement using compound mixtures (cassette dosing) as an alternative to single
      compound evaluation in order to increase the capacity of screens for intestinal
      drug permeability. Drug transport across Caco-2 monolayers was studied, both in
      the apical to basolateral and the basolateral to apical direction. The apparent
      permeability coefficients for ten compounds displaying different intestinal
      transport mechanisms were determined, first as single compounds and then as
      components of a mixture. Seven beta-adrenoceptor antagonists and baclofen were
      analysed simultaneously using reversed phase HPLC with UV detection, D-glucose
      and mannitol were measured by scintillation counting. The results indicated that
      the Papp from the mixture as donor phase correlated well with that of the single
      compounds and merely small changes in the Papp of each compound were observed
      between the single compound and mixture experiments. This minor variation
      resulted in a change in rank-order of the poorly permeable compounds in the
      mixture, however, without affecting their association with the permeability class
      according to the biopharmaceutics classification system (BCS). It can be
      concluded that the use of compound mixtures is a suitable method for improving
      the capacity in permeability screens. Further improvement of the throughput may
      be expected upon automatisation of permeability measurements using robotics
      combined with increased selectivity using LC-MS analysis.

PMID- 11338678
TI  - Antiviral activity of Australian tea tree oil and eucalyptus oil against herpes
      simplex virus in cell culture.
AB  - The antiviral effect of Australian tea tree oil (TTO) and eucalyptus oil (EUO)
      against herpes simplex virus was examined. Cytotoxicity of TTO and EUO was
      evaluated in a standard neutral red dye uptake assay. Toxicity of TTO and EUO was
      moderate for RC-37 cells and approached 50% (TC50) at concentrations of 0.006%
      and 0.03%, respectively. Antiviral activity of TTO and EUO against herpes simplex
      virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) was tested in vitro
      on RC-37 cells using a plaque reduction assay. The 50% inhibitory concentration
      (IC50) of TTO for herpes simplex virus plaque formation was 0.0009% and 0.0008%
      and the IC50 of EUO was determined at 0.009% and 0.008% for HSV-1 and HSV-2,
      respectively. Australian tea tree oil exhibited high levels of virucidal activity
      against HSV-1 and HSV-2 in viral suspension tests. At noncytotoxic concentrations
      of TTO plaque formation was reduced by 98.2% and 93.0% for HSV-1 and HSV-2,
      respectively. Noncytotoxic concentrations of EUO reduced virus titers by 57.9%
      for HSV-1 and 75.4% for HSV-2. Virus titers were reduced significantly with TTO,
      whereas EUO exhibited distinct but less antiviral activity. In order to determine
      the mode of antiviral action of both essential oils, either cells were pretreated
      before viral infection or viruses were incubated with TTO or EUO before
      infection, during adsorption or after penetration into the host cells. Plaque
      formation was clearly reduced, when herpes simplex virus was pretreated with the
      essential oils prior to adsorption. These results indicate that TTO and EUO
      affect the virus before or during adsorption, but not after penetration into the
      host cell. Thus TTO and EUO are capable to exert a direct antiviral effect on
      HSV. Although the active antiherpes components of Australian tea tree and
      eucalyptus oil are not yet known, their possible application as antiviral agents
      in recurrent herpes infection is promising.

PMID- 11338679
TI  - New methoxyflavone glycosides from Verbena bipinnatifida Nutt.
AB  - Two new methoxyflavone glycosides: chrysoeriol-7-O-(2,6-dirhamnosyl)-glucoside
      and chrysoeriol-7-O-neohesperidoside and seven other known flavonoids, were
      isolated and characterised from the aerial parts of Verbena bipinnatifida Nutt.
      (Verbenaceae). Their structures were elucidated by spectral and chemical methods
      of analysis.

PMID- 11338680
TI  - [Combination effect of arbekacin and cefepime on mixed culture of MRSA and P.
      aeruginosa].
AB  - We investigated the in vitro combination effects of arbekacin (ABK), vancomycin
      (VCM) or teicoplanin (TEIC) and cefepime (CFPM) on methicillin-resistant
      Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa isolated from various
      clinical specimens. Using checkerboard titration technique by agar dilution,
      combinations of ABK, VCM or TEIC and CFPM exhibited synergistic effects on 25
      MRSA strains. The similar effects were also observed on ABK-resistant MRSA.
      Combination of ABK and CFPM exhibited a good effect on P. aeruginosa, but
      combinations of VCM or TEIC and CFPM exhibited no synergistic effect on P.
      aeruginosa. In vitro bactericidal activities of ABK, VCM or TEIC and CFPM against
      mixed cultures of MRSA with P. aeruginosa were examined at concentration of each
      drug that corresponds to the serum concentration at 3 hours after the usual
      therapeutic dosage. VCM or TEIC alone showed bacteriostatic effects against MRSA,
      and no enhancements were observed when combined with CFPM. ABK alone showed good
      bactericidal activity against MRSA and combination with CFPM enhanced the
      bactericidal activity. Against P. aeruginosa, ABK or CFPM alone showed the
      bactericidal activity, and strong bactericidal activity was induced by the
      combination of ABK and CFPM. VCM and TEIC showed no bactericidal activities
      against P. aeruginosa. When CFPM combined with VCM or TEIC, the bactericidal
      activity of CFPM was not enhanced against P. aeruginosa.

PMID- 11338681
TI  - [Antimicrobial susceptibility of Pseudomonas aeruginosa isolated in Fukushima
      Prefecture].
AB  - We investigated the susceptibility of Pseudomonas aeruginosa (isolated from the
      sputum of patients with respiratory infection in 4 medical institutions in
      Fukushima Prefecture) to 8 beta-lactam antibiotics including three carbapenems
      and relationships among MICs of antibiotics tested. The MIC90 values for a total
      of 216 strains were 6.25 micrograms/ml for meropenem, 12.5 micrograms/ml for
      imipenem and ceftazidime, 25 micrograms/ml for panipenem and cefsulodin, 50
      micrograms/ml for cefpirome and over than 200 micrograms/ml for cefoperazone and
      piperacillin. The frequency of resistance of these strains to each antibiotic was
      as follows: The resistant strains were 19 (8.8%) for meropenem, 34 (15.7%) for
      imipenem and ceftazidime, 50 (23.1%) for cefsulodin, 72 (33.3%) for panipenem, 76
      (35.2%) for piperacillin and 90 (41.7%) for cefpirome. Eighteen strains (18.3%)
      of 19 meropenem resitant straisn were resistant to imipenem and panipenem, but 16
      strains of the 34 imipenem-resistant strains and 54 strains of the 72 panipenem
      resistant strains were susceptible to meropenem. In investigation of isolation of
      multi-resistant Pseudomonas aeruginosa, the susceptibility of strains tested to 7
      antibiotics except cefoperazone was as follows: The strains susceptible to all
      the 7 antibiotics were 92 strains (42.6%), and 33 strains (15.2%) were resistant
      to 2 antibiotics, 31 strains (14.4%) were resistant to 1 antibiotic, 21 strains
      (9.7%) were resistant to 3 antibiotics, 13 strains (6.0%) were resistant to 5
      antibiotics, 9 (4.2%) were resistant to 4 and 7 antibiotics, and 8 strains (3.7%)
      were reistant to 6 antibiotics. Since the emergence of these multi-resistant
      strains is closely related to frequent use of antibiotics for nosocomial
      infections, special attention should be paid to the antimicrobial susceptibility
      of Pseudomonas aeruginosa and the situation of antibiotic resistant strains.

PMID- 11338682
TI  - [Clinical effects of combination therapy with cefozopran and amikacin for
      infections in patients with hematological disorders].
AB  - Cefozopran (CZOP) and amikacin (AMK) were used concomitantly to treat infections
      complicated by hematological diseases. A total of 103 subjects were evaluated,
      and the all over efficacy rate was 69.9%. Acute leukemia was found in the largest
      number of patient, 57, followed by 29 cases of malignant lymphoma and 7 cases of
      myelodysplastic syndrome. By type of infection, patients having unknown origin
      were the largest in number, being 66, and the efficacy rate was 71.2%. The
      efficacy rates for sepsis, pneumonia and upper respiratory infection were 42.9%
      (7 cases), 71.4% (14 cases) and 90% (10 cases) respectively. The efficacy rates
      by neutrophil counts before administration of CZOP and AMK and at 1 week after
      administration were both 53.3% in the group of less than 100/microliter, both 60%
      in the group of less than 500/microliter. The efficacy rate by neutrophil counts
      at 1 week after administration was 58.6% in the group of less than
      100/microliter. The efficacy rate was 75.4% in the group of granulocyte colony
      stimulating factor (G-CSF) concomitant usage, and 61.9% in the group of non
      concomitant usage group. The efficacy rates by serum albumin levels before
      administration of CZOP and AMK and at 1 week after administration were both 92.9%
      in the group of over than 4 g/dl, both 50% in the group of less than 3 g/dl.
      Concomitant treatment with CZOP and AMK exhibited a high level of safety and
      efficacy rates in infections complicated by hematological diseases.

PMID- 11338683
TI  - [The clinical usefulness and transference of cefcapene pivoxil (CFPN-PI) into the
      maternal cubital blood, umbilical blood and amniotic fluid in premature rupture
      of the membranes].
AB  - We studied the transference of cefcapene pivoxil (CFPN-PI) into the maternal
      cubital blood, umbilical blood and amniotic fluid as well as its clinical
      usefulness. 58 pregnant women without complications who had a premature rupture
      of membranes after day 0 of the 36th week of pregnancy and delivered a child with
      a normal transvaginal labor were enrolled this study. As a result, we found that
      the maternal serum level of CFPN-PI reached a detectable level at 1 hr 15 min
      post dose, reached the maximum (Cmax) at 2 hr 30 min, and was maintained at 0.15
      1.14 micrograms/ml until 4 hr 35 min. In the umbilical serum, the drug
      concentration reached a detectable level at 1 hr 45 min post dose, was maintained
      at Cmax of 0.40 microgram/ml from 3 hr 3 min until 4 hr 27 min, and showed a
      level as high as 0.14 microgram/ml at 7 hr 7 min. In the amniotic fluid, the drug
      concentration reached a detectable level of 0.09 microgram/ml at 2 hr 48 min post
      dose, reached Cmax at 3 hr 55 min, and was maintained at 0.15-0.61 microgram/ml
      until 13 hr 37 min. Concerning the prophylactic effects of CFPN-PI against
      infections, one case of puerperal intrauterine infection in the parent and two
      cases of neonatal infection were observed, showing an effectiveness of 95%. In
      terms of adverse events, neither abnormality in maternal laboratory test data
      suspected as due to CFPN-PI, nor abnormality in subjective and objective findings
      was observed. In the neonates, no abnormality suspected as due to CFPN-PI was
      detected, either, including growth retardation until the 3-month medical
      examination. We think that CFPN-PI can be a first choice drug for prophylaxis of
      infections in cases of premature rupture of membranes after the 36th week of
      pregnancy, because of convenience of oral administration, coupled with excellent
      safety and potent prophylactic effectiveness against infections resulting from a
      long term maintenance of high levels in the umbilical blood and amniotic fluid.

PMID- 11338684
TI  - The interrelationship between human health and the environment cannot be
      overemphasized.

PMID- 11338685
TI  - A century that sets and a century that rises.

PMID- 11338686
TI  - Environmental health: a discipline in transition.

PMID- 11338687
TI  - Schoolboys in urban industrial environments: are they at increased risk of
      bronchial asthma?
AB  - The objective of this cross-sectional study was to compare the prevalence of
      bronchial asthma among Saudi schoolboys in Yanbu Industrial City and in two non
      industrial villages. In 1993, questionnaires were distributed to 375 schoolboys
      for completion by their parents. The prevalence of questionnaire-diagnosed asthma
      in Yanbu Industrial City, and in the villages of Al-Furash and Al-Gafure, was
      12.6%, 4.3% and 16% respectively. The prevalence of physician-diagnosed asthma in
      the three areas was 13.9%, 2.2% and 13.7% respectively. There was no significant
      difference between the two methods of diagnosis.

PMID- 11338688
TI  - Eosinophil cationic protein as a serological marker of disease activity in
      childhood bronchial asthma.
AB  - To study the value of eosinophil cationic protein (ECP) as a serological marker
      of disease activity in childhood bronchial asthma, ECP levels were measured in 20
      healthy control children and 25 asthmatic children, during and 2 weeks after
      acute exacerbation. The mean serum ECP level of all asthmatic patients, during
      and after exacerbation, was significantly higher than the control group and was
      significantly higher during attacks than 2 weeks after their termination. ECP
      levels were highest in severe attacks, but did not differ between mild and
      moderate attacks. ECP levels in asthmatic patients 2 weeks after mild and
      moderate attacks were comparable to normal; after severe attacks levels remained
      higher than normal. Measurement of serum ECP will be helpful in determining
      asthma activity and deciding the use of anti-asthma drugs.

PMID- 11338689
TI  - Epidemiological and risk predictors of severity of school injuries.
AB  - Accidents are the leading cause of morbidity and mortality among schoolchildren.
      Epidemiological and risk predictors of injury severity were investigated among
      all school injuries presenting at the Students' Hospital in Alexandria during the
      scholastic year 1996-97. In all, 3422 injured pupils were surveyed. Age, nature
      of injury, place and mechanism of school injury and referral method were
      significant risk predictors for hospitalization. Age, referral method and nature
      of injury were significant predictors of referral to specialized health services.
      Injury severity score was significantly predicted by the presence of acute
      disease during time of injury, place and mechanism of injury as well as by
      provision of first aid and referral method and time.

PMID- 11338690
TI  - Iranian rural health workers (behvarz) and risk factors of childhood injury.
AB  - The role of health professionals in childhood injury prevention has been
      recognized. This study aimed to assess the knowledge of and attitudes to
      childhood injury epidemiology and prevention of behvarz (rural health workers). A
      self-administered questionnaire was sent to 210 behvarz, randomly selected from
      rural areas of Khuzestan province. Many behvarz were not aware of the
      epidemiology of childhood injuries. However, they had positive attitudes towards
      all injury prevention activities. There was a positive correlation between their
      knowledge and attitude scores (P < 0.01). Childhood injury prevention programmes
      should be included in the training of behvarz and covered by primary health care
      programmes in the Islamic Republic of Iran.

PMID- 11338691
TI  - Effects of environmental tobacco smoke on the health of children in the Syrian
      Arab Republic.
AB  - In the Syrian Arab Republic, studies on the effects of environmental tobacco
      smoke on children are lacking. We conducted a cross-sectional study on the effect
      of household environmental tobacco smoke on 1859 children under 12 years from
      both urban and rural areas. Parental and household smoking were associated with
      respiratory morbidity in the children. Parental smoking was associated with an
      increased likelihood of having sudden infant death syndrome in the family and was
      also associated with the presence of other smokers within households, which adds
      to children's exposure. To our knowledge this is the first study in the Syrian
      Arab Republic to report a clear association between environmental tobacco smoke
      and childhood respiratory morbidity.

PMID- 11338692
TI  - Bionomics of anopheline vectors in Zabid District, Al-Hodeidah Governorate,
      Republic of Yemen.
AB  - The bionomics of anopheline vectors were analysed in randomly selected centres,
      representing fixed and spot-check stations. Three anopheline species were found.
      Anopheles arabiensis was the most prevalent species (84.2%) with a sporozoite
      rate of 0.7%, followed by A. culicifacies adenensis (14.9%) and A. rhodesiensis
      rupicolus (0.9%). Maximum indoor resting density was recorded during March, July
      and August. Positive sprayed sites for females were higher in bedrooms (40.4%)
      than animal sheds (26.9%). A total of 2560 anopheline larvae were collected of
      which 79.5% were A. arabiensis, 19.4% were A. culicifacies adenensis and 1.1% A.
      rhodesiensis rupicolus. A. arabiensis was assumed to be the most efficient
      malaria vector based on epidemiological evidence and the finding of natural
      sporozoite infected females.

PMID- 11338693
TI  - Clinical, laboratory and X-ray findings of drowning and near-drowning in the Gulf
      of Aqaba.
AB  - Clinical, laboratory and X-ray findings in 34 victims of submersion are
      presented. Five people died and 29 survived (age range 12-60 years). Severe
      hypoxia was found in all patients (mean PO2 of 58 mmHg with some oxygen support).
      Arterial blood gas analysis showed significant metabolic acidosis in 19 patients
      and significant respiratory acidosis in 15 patients. Pulmonary oedema was the
      most common X-ray finding. Fourteen patients were put on mechanical ventilation
      on the basis of their clinical picture and blood gases analysis. Clinical and
      laboratory data are very similar to those reported in international studies.

PMID- 11338694
TI  - Postvaccination mass psychogenic illness in an Iranian rural school.
AB  - In October 1992 after tetanus inoculations of 26 girl students in a village in
      the Islamic Republic of Iran, an outbreak of psychomotor syndrome occurred in 10.
      Although only few were affected, the temporary negative impact on public opinion
      about immunization was serious. Physical and laboratory investigations of the
      girls were normal. The 10 girls were compared with their 16 classmates. Higher
      socioeconomic status was protective (P = 0.04) and distance of home from school
      was relevant (P = 0.03). This is the first report of a health intervention
      unwarrantedly being held as the cause of an outbreak. The outbreak, however, was
      managed successfully.

PMID- 11338695
TI  - "Near miss" obstetric morbidity in an inner city hospital in Saudi Arabia.
AB  - A defined "near-miss" end-point, e.g. peripartum hysterectomy, is a more useful
      measure of obstetric care in a modern inner-city hospital than maternal
      mortality. Thus, indication(s), type of operation, risk factors and surgical
      morbidity of all cases of peripartum hysterectomy conducted over a period of 85
      months at King Abdul Aziz Hospital, Jeddah were reviewed. The incidence of
      hysterectomy was 1.22 per 1000 deliveries. Atonic postpartum haemorrhage was the
      most common reason (43.5%), followed by ruptured uterus (30.4%) and placenta
      accreta (26.1%). Of the atonic group, five patients were primigravidae, three of
      whom had severe pre-eclampsia. Abnormally prolonged labour was noted in this
      group. In the uterine rupture group, only two patients had had previous caesarean
      sections. In the placenta accreta group, three patients had placenta praevia, two
      of whom had scars from previous caesarean sections. One maternal death was
      attributed to amniotic fluid embolism.

PMID- 11338696
TI  - Ovarian cancer in Alexandria from 1988 to 1997: trends and survival.
AB  - The trend of incidence of ovarian cancer was studied, the 5-year survival rate
      calculated and prognostic factors for survival determined. Data were collected
      from the Alexandria Cancer Registry and medical records in various hospitals. A
      total of 358 cases of ovarian cancer were diagnosed from 1988 to 1997. A
      significant increasing trend in incidence of ovarian cancer from 1.23/100,000 in
      1988 to 3.16/100,000 in 1997 was found. The overall 5-year survival rate was 46%.
      The 5-year survival rates for tumour stages I to IV were 85%, 71%, 41% and 22%
      respectively, which was statistically significant. Survival rates with poorly
      differentiated tumours were significantly worse than with moderate or well
      differentiated tumours.

PMID- 11338697
TI  - Risk profiles for sexually transmitted diseases among patients attending the
      venereal disease clinic at Alexandria Main University Hospital.
AB  - Risk factors for sexually transmitted diseases (STDs) were assessed among 54 male
      and 36 female patients attending a venereal disease clinic. Sociodemographic data
      and information on sexual behaviour/STD history were collected. Patients were
      examined and specimens taken for laboratory diagnosis. Multivariate logistic
      regression analysis revealed that the significant predictors of genital
      infections among the male patients were: being unmarried, having multiple sexual
      partners, exposure to a symptomatic sexual partner, high frequency of intercourse
      per week, having repeated episode(s) of STDs and practising coitus interfemoris.
      In the female patients, exposure to a symptomatic sexual partner and high
      frequency of intercourse per week were the only significant predictors.

PMID- 11338698
TI  - Compliance and control of diabetes in a family practice setting, Saudi Arabia.
AB  - This study aimed to identify some determinants of compliance with diet, anti
      diabetic drugs and the appointment system amongst diabetic patients (n = 294)
      attending a family practice setting. The results showed that good compliance with
      diet was significantly higher among males (P = 0.01) and those with good diabetic
      control (P = 0.01), while good compliance with appointment systems was
      significantly associated with type II diabetes (P < 0.01) and good care (P <
      0.01). Compliance with drugs showed no significant association with any of the
      studied determinants (P > 0.05). When multiple regression analysis was applied,
      the degree of control of diabetes, its duration and the total score of care were
      the only predictors of the three aspects of compliance (P < 0.05).

PMID- 11338699
TI  - Lipid profiles in the Isfahan population: an Isfahan cardiovascular disease risk
      factor survey, 1994.
AB  - A population-based study was conducted in 1994 in Isfahan to define the
      prevalence of various types of hyperlipidaemia and the mean concentrations of
      serum total cholesterol, triglycerides, low-density lipoprotein cholesterol and
      high-density lipoprotein (HDL) cholesterol. In all, 2200 people were randomly
      chosen and classified into five age groups (20-70 years). The data were obtained
      by questionnaires and anthropometric measurements and serum lipids and fasting
      blood sugar were measured. The prevalence of hyperlipidaemia was higher in women
      than men. Multiple linear regression showed only HDL cholesterol and
      triglycerides to be associated with body mass index. The most prevalent lipid
      abnormality was HDL cholesterol. Diet modification and physical activity should
      be encouraged to reduce hyperlipidaemia.

PMID- 11338700
TI  - Emergency health services systems.

PMID- 11338701
TI  - Water conservation through Islamic public awareness in the Eastern Mediterranean
      Region.

PMID- 11338702
TI  - Lead, the ugly trace element: occurrence, effects, screening and treatment.

PMID- 11338703
TI  - Alexandria Healthy City and Women's Development Project.

PMID- 11338704
TI  - [Artificial water purification in the Sidi Mohammed Ben Abdellah reservoir dam in
      Morocco].

PMID- 11338705
TI  - Malaria: a question of an etiological role in diabetes mellitus.

PMID- 11338706
TI  - Non-neoplastic gastrojejunocolic fistula in a 68-year-old male patient.

PMID- 11338707
TI  - Ovale malaria: a case report from the Republic of Yemen.

PMID- 11338708
TI  - Detection of Mycobacterium tuberculosis complex and non-tuberculous mycobacteria
      by multiplex polymerase chain reactions.

PMID- 11338709
TI  - Environmental health in the Eastern Mediterranean.

PMID- 11338710
TI  - Foot-and-mouth disease: outbreaks exceed 1000.

PMID- 11338711
TI  - Antibiotic resistance: Lords call for further action 'on the ground'.

PMID- 11338712
TI  - Animal welfare problems arising as a result of FMD: short-term solutions.

PMID- 11338713
TI  - Inconsistent detection of PrP in extraneural tissues of cats with feline
      spongiform encephalopathy.
AB  - Feline spongiform encephalopathy (FSE), a transmissible spongiform encephalopathy
      or prion disease of cats, first reported in Great Britain in 1990, is believed to
      result from the consumption of food contaminated by the agent of bovine
      spongiform encephalopathy (BSE). The accumulation of PrP in non-neural tissues of
      cats diagnosed as suffering from FSE was investigated by immunohistochemistry. In
      the majority of the cats no disease-specific PrP was detected in lymphoid
      tissues. Small amounts of PrP were detected in the spleen of only two of 13
      samples examined, in Peyer's patches of one of the two cases for which suitable
      material was available, but in the myenteric plexus of all four cats in which
      sections of intestine were examined. In addition PrP immunostaining was found in
      the kidney of all the cats with FSE whose kidneys were examined.

PMID- 11338714
TI  - Analgesic effects in dogs of carprofen and pethidine together compared with the
      effects of either drug alone.
AB  - Thirty bitches undergoing routine neutering were used in an assessor-blinded
      trial of the postoperative analgesic effects of pethidine and carprofen
      administered either together or singly. The level of analgesia was assessed by
      visual analogue scale (VAS) scores for pain and sedation and by nociceptive
      mechanical threshold testing. The two drugs administered together, and carprofen
      alone, provided good postoperative analgesia as assessed by VAS scoring.
      Pethidine alone did not provide postoperative analgesia of sufficient duration.

PMID- 11338715
TI  - Systematic review of evidence for the prevalence of food sensitivity in dogs.
AB  - Twelve papers giving original data on canine food sensitivity in an acceptable
      form were reviewed, and the disorder was confirmed in 390 dogs. Most of the
      papers did not give either the criteria by which dogs were included in a trial,
      or information about dogs which had undergone a trial with a restricted diet but
      in which food sensitivity had not been observed. Only one author indicated how
      the degree of pruritus of the dogs in the study was assessed. The question of
      owner compliance in conducting a diet trial was not considered in any of the
      papers. The best available evidence comes from three of the studies covering 534
      dogs in total, of which 93 (17 per cent) suffered food sensitivity.

PMID- 11338716
TI  - Follow up of feline immunodeficiency virus-infected cats.

PMID- 11338717
TI  - Nasal dermatitis as a manifestation of canine pemphigus vulgaris.

PMID- 11338718
TI  - Detection and isolation of a flavivirus-like agent from a leopard tortoise
      (Geochelone paradalis) in the United Kingdom.

PMID- 11338719
TI  - Animal medicines and FMD.

PMID- 11338720
TI  - Animal medicines and FMD.

PMID- 11338721
TI  - Preventing future ingress of FMD virus.

PMID- 11338722
TI  - VLA submission forms.

PMID- 11338724
TI  - Getting into hot water.

PMID- 11338723
TI  - A randomized, double-blind, multicenter trial comparing fluticasone propionate
      cream, 0.05%, and hydrocortisone-17-butyrate cream, 0.1%, applied twice daily for
      4 weeks in the treatment of psoriasis.
AB  - The efficacy, safety, and tolerability of twice-daily fluticasone propionate
      (Cutivate) cream, 0.05%, and hydrocortisone-17-butyrate cream, 0.1%, were
      compared in 125 patients with moderate-to-severe psoriasis in a 4-week,
      multicenter, double-blind, randomized, active-control study. Clinical assessments
      of response to therapy, made at weekly intervals, included physicians' gross
      assessment of clinical response, improvement in signs and symptoms, and patients'
      assessment of treatment effects. Based on physicians' gross assessment,
      fluticasone propionate cream was superior to hydrocortisone-17-butyrate cream at
      day 22 (after 3 weeks' treatment) and at the end-of-treatment visit (P < .05).
      Cleared, excellent, or good end-of-treatment response rates were 50/63 (79%) for
      fluticasone propionate compared with 41/60 (68%) for hydrocortisone-17-butyrate.
      Adverse events were limited to mild-to-moderate pruritus with fluticasone
      propionate (3.2%) and hydrocortisone-17-butyrate (1.7%) and mild skin warmth with
      hydrocortisone-17-butyrate (1.7%).

PMID- 11338725
TI  - Achieving low germ concentrations.
AB  - The laminar outlet for operating theatres, presented here, which is being used to
      generate a laminar downflow, produces a very stable air pattern at air discharge
      velocities of = 0.15 m/s. Air flow tests show that the influence on air flow by
      operating lightings in the flow field is localised. Based on these results,
      recommendations can be made for the placement of operating lighting under the
      laminar outlet. Hygienic tests to DIN 4799 recorded relative airborne germ
      concentrations that comfortably meet the requirements of DIN 1946 Part 4, even at
      an air discharge velocity of 0.15 m/s.

PMID- 11338726
TI  - Environmental impact assessment and estates strategy.

PMID- 11338727
TI  - Making IT better.
AB  - The body of the healthcare sector is today supported by a nervous system of
      advanced technology infrastructure that has become vital to its efficient
      operation. The sharing of information between hospitals, clinics, surgeries and
      administrative units has become a key part of the everyday activities of the
      sector, streamlining processes and giving healthcare professionals access to
      stored knowledge that would otherwise be unavailable. Supporting this 'nervous
      system' are the companies that supply and maintain the networks and technology on
      which the sector now relies.

PMID- 11338728
TI  - Public health and personal health: the concept of new family medicine and re
      orientation of primary health care to face the challenges in the 21st century.

PMID- 11338729
TI  - The role of APACPH (Asia-Pacific Academic Consortium for Public Health) in
      addressing public health issues in the Asia-Pacific region.
AB  - The paper covers the establishment of APACPH in 1984 and its subsequent
      development and achievements. The paper outlines the mission and objectives of
      the Consortium and brief comparisons are drawn with similar organizations in the
      European and North American regions. Significant achievements of the Consortium
      and its contribution to the public health debate are presented. The paper then
      explores strategies for the future in meeting the challenges of emerging public
      health issues through collaborative efforts in education, training, research and
      leadership development in public health in the first century of a new millennium.

PMID- 11338730
TI  - Health education--Hong Kong's experience.
AB  - The HKSAR Department of Health is the Government's health adviser and agency to
      execute health care policies and statutory functions. It safeguards the health of
      the community through promotive, preventive, curative and rehabilitative
      services. The Department invests in health promotion activities and discharges
      its functions through three designated units, namely the Central Health Education
      Unit, Oral Health Education Unit and the Red Ribbon Centre for AIDS education, as
      well as through client contacts at primary and specialised health care centres.
      The Department is set to enhance its health information base, advocate for
      intersectoral collaboration and community participation in health, and engage in
      wider research and evaluation of health promotion interventions.

PMID- 11338731
TI  - Public health nutrition: results and research.
AB  - Public health nutrition is focused on the prevention of diet-related diseases and
      the attainment of good health, through policy, education and health promotion. It
      involves many sectors of the community, cooperating to improve the health and
      wellbeing of the population with emphasis on prevention, equity, wellbeing and
      improved quality of life. In the majority of western countries, an epidemic of
      coronary heart disease (CHD) began after World War One, reaching its peak in the
      1970's. In Asia, the epidemic began after WW2 with the rapid economic development
      of the region. In western countries, of which Australia is a typical example,
      health promotion activities and improved hospital treatment have been effective
      in reducing the impact of the CHD epidemic. The life expectancy of the population
      has steadily grown to 75.6 years for males and 81.3 years for females. Despite
      major advances in the prevention and treatment of cardiovascular disease, it is
      still the leading cause of premature mortality and morbidity in Australia.
      Furthermore, cardiovascular disease shares common risk factors with other leading
      causes of death, including lifestyle behaviours (diet, physical inactivity,
      alcohol consumption, smoking), physiological states (obesity, hypertension, high
      blood cholesterol) and socioeconomic factors. For Asia, the challenge is to
      implement public health policies that will tackle the epidemic of chronic disease
      before it reaches its peak. Health Promotion policies will be important for all
      countries. The use of the disability adjusted life years (DALY) methodology to
      measure the association between the cause of disease and relate its occurrence to
      health outcomes will be an important public health planning tool.

PMID- 11338732
TI  - Training and research for implementation of health care system reform in
      Cambodia.
AB  - One important objective of Technical Co-operation is institutional strengthening.
      Human resource development is understood as a means of improving the
      implementation of health care system development and an important factor for
      sustainability. Health care system reform is also a concern in Cambodia, where it
      has suffered from a period of war and insecurity previously, and now is beginning
      to aim for long term development. The implementation of the reform started four
      years ago with external support. This paper will show how capacity can be built
      and services developed under the specific circumstances of Cambodia, with
      technical cooperation and support from neighbouring countries through the SEAMEO
      TROPMED network. Training courses have been developed and research studies have
      been conducted to strengthen the role of the National Institute of Public Health
      and to aim for quality improvement. In addition, impact of training to improve
      management at provincial/district level was measured.

PMID- 11338733
TI  - Epidemiology of health changes in older women in Hong Kong.
AB  - This paper aims to present the baseline social, mental and functional
      characteristics, the changes of these characteristics over a 36-month follow-up
      period, and the issues and implications related to these changes, particularly in
      older women. The cohort comprising 2030 subjects aged 70 and above has been
      assembled by stratified disproportional random sampling. Registrants with the Old
      Age Allowance Scheme, which has over 90 percent coverage of the Hong Kong elderly
      population, was used to define the accessible population. Face-to-face interviews
      were conducted at the respondents' place of residence. A number of social and
      health variables were collected at baseline. The surviving subjects had been
      followed up at 36 months and repeated measurements of the baseline variables were
      obtained. Older women were over-represented by low level education, financial
      dependency, as well as residence in institutions. Women had higher prevalence as
      well as incidence of musculoskeletal problems. While there was a general decline
      in health and social support in the elderly cohort, we observed a preponderance
      of older female subjects with mental and functional decline over the follow-up
      period. An overrepresentation of female subjects with depressive symptoms at
      baseline and follow-up was also noted. The descriptive data have revealed a host
      of social and health changes over a three-year follow-up period. Women aged 80
      years and above formed a particularly disadvantaged group. The results will have
      direct implications for the shaping of social and health policy for strategic
      planning of priorities in social and health care services.

PMID- 11338735
TI  - The role of the new School of Public Health of the Chinese University of Hong
      Kong in public health education.
AB  - In recent years there have been several major outbreaks of infectious diseases in
      Hong Kong due to deteriorating environmental hygiene, food hygiene and
      environmental pollution. Aging of the population has resulted in a growing
      prevalence of chronic degenerative diseases. Changes in behaviour and socio
      economic environment have also resulted in many diseases associated with
      lifestyle such as smoking, substance abuse and obesity. Hong Kong has a long
      history of medical education and well-established academic institutions for the
      training of doctors. However, there is still up to now no academic health
      institution specially designed and built dedicated solely and fully to public
      health education. A School of Public Health is therefore urgently needed in Hong
      Kong to provide training and education of public health professionals, to learn
      new approaches, to discover new solutions and develop new services through
      research and discovery.

PMID- 11338734
TI  - Overview of occupational health research in Hong Kong.
AB  - A review was undertaken to collect and collate information on studies that have
      been done in Hong Kong in the field of occupational health. Both published and
      unpublished reports related to occupational health research in Hong Kong during
      the period 1966-1997 were sought. The data collection was performed through
      various means, including electronic Medline searches and manual searches of local
      academic and professional journals. Relevant information for each report was
      abstracted and collated. A total of 357 studies/reports related to occupational
      health in Hong Kong were identified during the period 1964 to 1997. Few reports
      were available before 1980. Roughly similar numbers of reports were found for
      chemical hazards, dust and ergonomics (including psychosocial factors). In
      addition, there were substantial numbers of reports on physical hazards. Organic
      solvents, silica dust, compressed air and noise were the specific hazards more
      frequently reported. The manufacturing and construction industries were the more
      frequently studied groups. Recent studies have focused more attention on the non
      industrial sectors, including the service sector, offices, schools, hospitals and
      transport. The vast majority of the reports were based on cross-sectional
      surveys. A significant number of published reports were discussion or review
      papers. Most studies were less than adequate in terms of documenting causal
      relationships. Despite the limited resources, occupational health researchers in
      Hong Kong have made great achievements in the past decades. The study subjects
      and the numbers of studies reflected major health problems accompanying the
      development and changes of local industries and trades from time to time.

PMID- 11338736
TI  - Overall view of occupational health services in Korea.
AB  - Occupational health services in Korea can be largely divided into periodic health
      examination for workers, group health care system for workers in small and medium
      size industries, and workplace environment measurement. Periodic health
      examination is composed of general and special health examination. General health
      examination is performed once every two years for office workers and once every
      year for production workers. The expenses of medical examination are covered by
      public medical insurance program. Special health examination is performed on
      workers who dealt with hazardous agents with variable durations. The employer
      pays the expense of special health examination. Group health care system has been
      established for small and medium sized industries exempt for assignment of full
      time health managers (physician, nurse, hygienist). It entrusts the role of
      health managers to occupational health organization or clinic. Especially,
      entrust fee of small sized industries are paid by government. The levels of
      hazardous agents are measured in all workplace environment. If the measured level
      exceeds the permissible exposure level, the employer is enforced to improve the
      workplace environment with their own expense. In 1997, 684,000 workers received
      periodic health examination and 2,400 workers were found with occupational
      diseases.

PMID- 11338737
TI  - Research on air pollution and health in Hong Kong.
AB  - The relation between air pollution and health was reviewed with reference to
      major air pollution incidents that occurred in the early to mid-twentieth
      century, and the more recent findings of health effects at relatively low
      concentrations of air pollutants. Findings of epidemiological studies in Hong
      Kong on air pollution and health were then described. These range from cross
      sectional studies, before-and-after study, and the popular time series studies.
      In general, results concurred with findings reported in many overseas studies.
      Future research needs include the study of health effects in the primary care
      setting, exposure assessment studies, panel studies, health economic studies, and
      experimental studies for the detection of threshold levels of exposure.

PMID- 11338738
TI  - Flexible delivery of education in environmental health.
AB  - The promotion of environmental health is essential for the well-being of present
      and future communities. However, environment and health are still two areas that
      many organisations and governments find it difficult to fully integrate, and
      there is a need to focus more on the management of environmental health issues
      for public health practitioners. The continuous education and training of public
      health professionals, to incorporate environmental health into their management
      strategies, is the first step to achieve a stronger focus on the prevention of
      environmental health problems, rather than identification and evaluation of
      current problems. As most of the practitioners are in employment and may not be
      able to find the time or the money to study full time to improve their
      capabilities, the option to study externally and in their own time, in addition
      to their day time work, is required.

PMID- 11338739
TI  - Making a difference to the socioeconomic determinants of health: policy responses
      and intervention options.
AB  - APACPH has previously highlighted the profound effect of global economic change
      on increasing health disparities in most countries in the Asian Pacific Region of
      the world, with those citizens who are most disadvantaged and vulnerable,
      suffering most. This presentation identifies two key issues that should underpin
      efforts to reduce socioeconomic health disparities: (1) the current evidence base
      on policies and interventions successful in reducing inequalities; and, (2) how
      to implement such strategies. Actions to reduce such disparities should ideally
      include: (1) changes in macro-level social and economic policies, (2) improving
      living and working conditions, (3) strengthening communities for health, (4)
      influencing behavioural risk factors, (5) strengthening individuals and their
      social networks, and (5) an improved response from the health care system and
      associated services. Other than a few notable exceptions, few countries have
      developed a coordinated and integrated approach to addressing health
      inequalities. However, previously successful public health interventions
      represent a good starting point. Health professionals have an important role to
      play in not only recognising that the determinants of health are rooted in the
      economic, social and cultural fabric of our society, but in supporting and
      advocating strategies and approaches that lie upstream from the health care
      system.

PMID- 11338740
TI  - Youth health promotion and health promoting schools: what should be the aims?
AB  - The school plays a very important role in health education and promotion at the
      crucial stage of childhood and adolescence. It develops personal character,
      skills, attitude and physique, in addition to imparting knowledge. To sustain the
      concerted effort to address inter-wined social, educational, psychological and
      health needs of children, training and ongoing reinforcement must be given to
      teachers. A task force made up of parents, teachers, administrators, students and
      health professionals must be formed to develop core values, visions, goals and
      activities; and to provide new direction for health education and promotion. The
      'Health Promoting Schools' Programme of the CUHK was launched in 1999 with the
      aim to promote physical, emotional and intellectual development of students
      through healthy and hygienic practices. The programme has also conducted
      researches on health of students, prioritise and evaluate relevant programmes.
      Recent research studies revealed that students in higher grades had more physical
      and psychological health problems, probably due to heavy workload and less
      emphasis on health education in their formal curriculum. Another research study
      has shown the lack of concrete school policies in health education. It is
      therefore important to develop policies, practices and structures, as well as
      regular curricular reviews to promote health of the school children. The "Health
      Promoting Schools' Programme has already initiated several district based health
      promotion programmes to pave the way for the formation of local task force on
      youth health promotion.

PMID- 11338742
TI  - Public health medicine training in Singapore.
AB  - Public health as a discipline is difficult to characterize because it has to
      respond to changes in human societies. As such, public health training has two
      dimensions--(1) Orientation and (2) Competencies. Our orientation should be broad
      and multidisciplinary to keep "alive the idea of improving the public health as a
      primary value". On the other hand, competencies define our professional status
      and role, which are focused mainly on our work on status of health, surveillance
      and disease control, health services and their evaluation. The core competencies
      can be organized according to the following categories: (1) Epidemiologic, (2)
      Programme-based, (3) Laboratory-based and (4) Practice-based. The Singapore
      Programme is a 6-year post-intern medical training, with core components and
      electives clustered around 2 themes: (1) Health Policy and Management, (2)
      International Health.

PMID- 11338741
TI  - Sexual health education for youths--a Malaysian experience.
AB  - A survey was conducted to assess student's sexual knowledge and attitudes using a
      questionnaire based on the Sex Knowledge and Attitude Test (SKAT-II) to compare
      medical and nursing students with students (non-medical/nursing) who registered
      for a sexual health course. 85 Sexual Health, 115 medical and 81 nursing students
      voluntarily participated in the survey. This study showed that all the student
      groups showed relatively low scores in knowledge. Furthermore, average knowledge
      scores differed significantly between the three student groups with medical
      students scoring highest and nursing students lowest. Besides student groups,
      several other factors were found to be significantly associated with Knowledge
      score namely, race, religion, age, perception of the importance of religion and
      the extent to which religious beliefs influence sexual attitudes. Furthermore,
      multivariate statistical analyses showed that among these factors, student group,
      race/religion and religious importance were significant predictors of sexual
      knowledge. Specifically, being a medical student was associated with higher
      scores relative to a non-medical student, being a Malay student was independently
      associated with a lower average score compared to other races, and perceiving
      religion as extremely important was associated with a lower score.

PMID- 11338743
TI  - Healthy City Kwachon 21 Project: a community health promotion programme in Korea.
AB  - Disease patterns of Koreans changed from infectious disease to non-infectious
      disease in the 1970's. Even though there has been a need for a health promotion
      programme, it was hard to find the programme in the community before 1985 in
      Korea. In 1985, the Public Health Promotion Law was enacted and the Korean
      government started to encourage local government to plan and conduct community
      health promotion programs. Healthy City Kwachon 21 (HCK21) is a health promotion
      programme for all residents in Kwachon, a city which has about 70,000 population
      and is located adjacent to Seoul, Korea. HCK21 launched in 1998 with three
      guiding principles: 1) programs should be accessible to all citizens; 2)
      Programmes should stimulate strong community participation and 3) Programmes
      should change environment and society. The long term goal of HCK21 is to increase
      the healthy life span of citizens in Kwachon. HCK21 is a collaborative project
      between Kwachon and the Institute for Health Promotion of the Graduate School of
      Health Science and Management, Yonsei University. It has seven components: 1)
      Publication of Monthly Health Newsletter; 2) Smoking Cessation and Tobacco
      Prevention Program; 3) Community Nutrition Program; 4) Maternal and Women's
      Health Programme; 5) Programme for Development of District Health Management
      Information System; 6) Hypertension Prevention and Control Programme and 7)
      Physical Activity Programme. HCK21 is now being implemented in the third year
      program since the program conducted in 1998 and 1999 was successful with received
      support from the citizens. It is recommended that HCK21 be a model for an
      integrated community-based health promotion programme in developing countries.

PMID- 11338744
TI  - Controlling health care costs whilst improving population health: what are the
      issues and can it be done in Hong Kong?
AB  - Many countries are experiencing two related types of 'transition', one leading to
      Improved Population Health, but the other leading to Rising Health Care Costs.
      This paper will present and discuss a conceptual framework for each of these
      trends, which illustrate key factors that are, or may be, contributing to such
      outcomes. Factors contributing to improved population health include: health
      promotion and disease prevention; effective public health; effective housing
      policies. Factors contributing to Rising Health Care Costs include: demographic
      transition, increasing life expectancy; medical technology. Hong Kong is
      currently digesting the recommendations of the 'Harvard Report', which considered
      future options for meeting the following five reform objectives: (1) Maintaining
      and improving equity; (2) Improving quality and efficiency; (3) Improving
      financial sustainability; (4) Meeting the future needs of the population; (5)
      Managing overall health expenditure inflation. As can be seen, the two related
      transition trends of improved population health and rising health care costs are
      reflected in these objectives. The Harvard Report recommends a Competitive
      Integrated Health Care option as the most appropriate 'solution' for Hong Kong in
      the long run. The paper will briefly comment on this proposal.

PMID- 11338745
TI  - Gender issues in medical and public health education.
AB  - There is no doubt that gender bias has been inherent in medical and public health
      education, research, and clinical practice. This paper discusses the central
      question for medical and public health educators viz. whether women's health
      concerns and needs could be best addressed by the conventional biomedical
      approach to medical and public health education, research, and practice. Gender
      inequalities in health and gender bias in medical and public health education are
      revealed. It is found that in most public health and prevention issues related to
      women's health, the core issue is male-female power relations, and not merely the
      lack of public health services, medical technology, or information. There is,
      thus, an urgent need to gender-sensitize public health and medical education. The
      paper proposes a gender analysis of health to distinguish between biological
      causes and social explanations for the health differentials between men and
      women. It also assessed some of the gender approaches to public health and
      medical education currently adopted in the Asia-Pacific region. It poses the
      pressing question of how medical and public health educators integrate the gender
      perspective into medical and public health education. The paper exhorts all
      medical and public health practitioners to explore new directions and identify
      innovative strategies to formulate a gender-sensitive curriculum towards the best
      practices in medicine and public health that will meet the health needs of women
      and men in the 21st century.

PMID- 11338746
TI  - Sexual issues of the disabled: implications for public health education.
AB  - Sexuality of persons with spinal cord injury has received increased attention
      especially in the Western countries. However, in the local context, studies
      pertaining to the sexuality of the disabled are almost nil. This paper utilized a
      qualitative approach in assessing sexual knowledge, attitudes and practices of
      persons with spinal cord injury. Eight focus group discussions consisting of 28
      adult spinal cord injured persons were carried out. The results showed that the
      frequency of sexual activity decreased following injury. The disabled themselves
      have a negative self-concept and a low self-esteem and this affects their
      attitudes towards sexuality and their sexual behaviour. Health care professionals
      tend to neglect this issue perhaps due to their insensitivity to the sexual needs
      for the disabled or a lack of understanding and expertise in this area. A need
      for sexual information related to their disability is warranted in the areas of
      reproduction, contraception and their ability/disability in achieving an erection
      or ejaculation. This study indicated a need for more comprehensive research in
      this neglected area of sexual issues of persons with disabilities. Public health
      education and counseling is deemed necessary for the disabled themselves so as to
      accommodate their sexual lives to their physical capabilities and desires.
      Attitudes and misconceptions of the public need to be corrected. Above all, there
      is a need for education and training for health care professionals in the area of
      sexual rehabilitation, which is currently non-existent in the country. Perhaps,
      it is timely to incorporate sexual rehabilitation as part of a holistic medical
      rehabilitation of the disabled.

PMID- 11338747
TI  - Global health challenges: trends in public health training, research and
      advocacy.
AB  - As we begin the 21st century, public health is at the crossroads in trying to
      understand the relative importance of health determinants in risk exposures, and
      the collective susceptibility of our societies. Classically conditioned attitudes
      of investigation, instruction, and exposition in the management of acute disease
      breaks down, when disease surveillance becomes virtually useless as in the
      prevention of chronic conditions. Older populations, new lifestyle changes,
      environmental hazards and urbanization have converged to make social class and
      poverty predominant factors in the expression of morbidity and mortality. In the
      process, the comfort of specific disease eradication is replaced by continuous
      challenges in dealing with the dynamics of social change--behaviors in diet and
      exercise--as well as the globalization of poverty, addiction, injury and
      violence. The consequent dilemma to develop a base for public health
      intervention, a strategy for training and a platform for advocacy for health
      improvement shows an eclectic pattern. The traditional clinically oriented
      perspective has moved towards a comprehensive population-based disease management
      model. A second trend with a somewhat narrowed vision for public health is the
      one focused on cost containment limiting preventive care. As technological
      advances in genetics and medicine and health informatics brings more rational,
      evidence based management in health care, two major gaps in public health
      training continues to persist. One is the lack of adequate attention to social
      class and poverty as a major pervasive factor. The other relates to the inability
      to address effectively, injury, violence, and mini wars diluting the value
      perspectives and advocacy in public health.

PMID- 11338748
TI  - Truth in advertising.

PMID- 11338749
TI  - Cancer pain management.

PMID- 11338750
TI  - Patients' bill of rights for quality cancer care. Oncologic Nursing Society.

PMID- 11338751
TI  - The nurse's responsibility to the patient requesting assisted suicide. Oncologic
      Nursing Society.

PMID- 11338752
TI  - Instructor receives inquiry regarding article on foot reflexology and cancer.

PMID- 11338753
TI  - Another reader shares experience with paclitaxel reactions.

PMID- 11338754
TI  - Bone marrow transplant teaching rounds: promoting excellence in nursing care.

PMID- 11338755
TI  - Symptom clusters and their effect on the functional status of patients with
      cancer.
AB  - PURPOSE/OBJECTIVES: To determine the effect of the symptom cluster of pain,
      fatigue, and sleep insufficiency on functional status during three cycles of
      chemotherapy. DESIGN: Prospective, longitudinal. SETTING: 23 outpatient offices
      and clinics. SAMPLE: 93 patients with cancer. The typical participant was female
      (72%), married/partnered (65%), white (87%), and middle-aged (55.4 years), with
      an average of 14.8 years of education. METHODS: The Quality of Life-Cancer (QOL
      CA) version instrument and the Karnofsky Performance Scale (KPS) were completed
      by 93 outpatients receiving chemotherapy at baseline (Time 1) and at the end of
      the third cycle (Time 2). Three items (pain, tires easily, sleeps enough to meet
      needs) from the QOL-CA questionnaire were used to measure the symptom cluster.
      MAIN RESEARCH VARIABLES: Symptom cluster, outcome, functional status,
      chemotherapy. FINDINGS: A hierarchical multiple regression model explained 48.4%
      of the variance in functional status. The KPS at Time 1 explained 30.8% of the
      variance in KPS at Time 2 (p < 0.001). After KPS at Time 1 was partialled out
      from KPS at Time 2, the four independent variables entered in the next step were
      considered predictors of the change in functional status between Time 1 and Time
      2. Age explained 11.8% of the change (p = 0.001), pain explained 10.7% of the
      change (p = 0.002), and fatigue explained 7.3% of the change (p = 0.011). Sleep
      insufficiency statistically was not significant, only explaining 1% of the change
      (p = 0.344). CONCLUSION: This study provides beginning insights into the effect
      of a symptom cluster on patients' functional status. IMPLICATIONS FOR NURSING
      PRACTICE: Healthcare professionals need to be aware of the presence of symptom
      clusters and their possible synergistic adverse effect on patients' future
      morbidity.

PMID- 11338756
TI  - Thalidomide use: past history and current implications for practice.
AB  - PURPOSE/OBJECTIVES: To review the history of thalidomide, examine fears emanating
      from its renewed usage, and discuss the nurse's critical role in patient
      education. DATA SOURCES: Published articles, abstracts, books, and clinical
      experience. DATA SYNTHESIS: In the early 1960s, the teratogenic effects of
      thalidomide became widely known. The words thalidomide and birth defects became
      permanently linked as a result of pregnant women who used thalidomide as a
      sedative, thus giving birth to children with horrific birth defects. As
      researchers look at novel properties of drugs and new indications in the
      oncologic setting, thalidomide has made a comeback, particularly in the treatment
      of multiple myeloma. Patient education is important to combat fear in using and
      prescribing thalidomide and is essential in preventing birth defects and other
      side effects associated with thalidomide use. CONCLUSIONS: Nurses are vital in
      the patient-education process, yet on extensive nursing literature search
      revealed limited publications regarding thalidomide. Nurses can prevent
      thalidomide-associated birth defects through comprehensive patient education and
      can assist patients in decreasing any anxiety related to potential and actual
      side effects. IMPLICATIONS FOR NURSING PRACTICE: With careful patient monitoring
      and comprehensive education of physicians, nurses, and patients, it is possible
      to reap the benefits of thalidomide and avoid the tragedy of misues. Nurses are
      in the forefront of education, and their expertise will empower patients to use
      thalidomide responsibly.

PMID- 11338757
TI  - Posttraumatic stress, quality of life, and psychological distress in young adult
      survivors of childhood cancer.
AB  - PURPOSE/OBJECTIVES: To explore the relationship between posttraumatic stress
      disorder (PTSD) and quality of life (QOL)/psychological outcome in young adult
      survivors of childhood cancer. DESIGN: Cross-sectional, descriptive study.
      SETTING: A large comprehensive pediatric cancer center on the West Coast. SAMPLE:
      Fifty-one young adult survivors of childhood cancer, 18-37 years of age, disease
      free, and off treatment for an average of 11 years (range 2.8-26.7 years).
      METHODS: A structured clinical interview was used to establish a PTSD diagnosis.
      Self-report instruments were used to assess QOL (RAND SF-36) and psychological
      distress (Brief Symptom Inventory (BSI)). Survivors with and without PTSD were
      compared on the BSI and RAND SF-36. MAIN RESEARCH VARIABLES: PTSD status, QOL and
      psychological distress. FINDINGS: Eleven subjects (20%) met full criteria for
      PTSD. Significant group differences were found for 17 of the 18 outcome
      variables. Survivors with PTSD reported clinically significant levels of
      psychological distress, whereas symptom levels for those without PTSD fell well
      within population norms. On all domains, QOL scores were significantly lower for
      the PTSD group compared to the non-PTSD group. CONCLUSIONS: PTSD in survivors of
      childhood cancer is related to long-term outcome. PTSD is associated with a
      poorer QOL (physical and mental) and an increase in psychological distress. Data
      suggest that survivors with PTSD have significant functional limitations and
      psychological comorbidity. IMPLICATIONS FOR NURSING PRACTICE: Screening cancer
      survivors for PTSD will identify high-risk patients who need further evaluation
      and intervention.

PMID- 11338758
TI  - Metastatic breast cancer: understanding current management options.
AB  - PURPOSE/OBJECTIVES: To review the standard treatment options for metastatic
      breast cancer, present recently approved chemotherapeutic and hormonal
      approaches, and describe novel biologic therapies, particularly the use of
      monoclonal antibodies. DATA SOURCES: Published articles, abstracts, and
      conference proceedings. DATA SYNTHESIS: Standard treatment options available to
      women with metastatic breast cancer include surgery, radiation therapy, hormonal
      therapy, chemotherapy, and palliative approaches. New chemotherapeutic approaches
      for the management of metastatic breast cancer include the recently approved
      agents paclitaxel, docetaxel, and capecitabine. New hormonal agents such as
      toremifene, letrozole, and exemestane also have been approved. Finally, an agent
      from a new class of agents--biologic response modifiers (BRMs)--now. Is
      available. Trastuzumab, a monoclonal antibody (one class of BRMs), is a new and
      promising approach available to a subpopulation of women with metastatic breast
      cancer. CONCLUSION: Although standard treatment options for the management of
      metastatic breast cancer may prolong survival for some, they have not resulted in
      a cure for the majority of women. Recent advances in the understanding of cancer
      cellular biology have led to newer approaches such as monoclonal antibodies and
      other BRMs that may offer hope of extended survival and improved quality of life
      for certain women. This field is growing quickly, and new targets for breast
      cancer therapy are being studied. IMPLICATIONS FOR NURSING PRACTICE: Nurses who
      become familiar with newer treatment options available for the management of
      metastatic breast cancer, including new chemotherapeutic and hormonal approaches
      and monoclonal antibody therapy, are better able to provide information and
      support for their patients. Clinicians must understand the criteria for patient
      selection for newer agents, particularly trastuzumab. In addition, recognizing
      adverse effects and knowing the management strategies for treatment-related
      toxicities help to ensure positive patient outcomes.

PMID- 11338759
TI  - African American women's experiences with the initial discovery, diagnosis, and
      treatment of breast cancer.
AB  - PURPOSE/OBJECTIVES: To describe the experiences of African American women living
      with breast cancer following the primary diagnosis and while undergoing initial
      treatment. DESIGN: Phenomenologic. SAMPLE/SETTING: 13 African American women
      (ages 30-66) purposefully selected from two oncology clinics in the mid-South.
      METHODS: Phenomenologic interviews (transcribed verbatim) and field notes were
      analyzed using Colaizzi's method of phenomenologic description and analysis.
      FINDINGS: Experience Trajectory, Femininity, and Spirituality were the three
      major themes. The Experience Trajectory subthemes were finding the lump, getting
      the diagnosis, undergoing surgery and adjuvant treatment. The Femininity
      subthemes were loss of all or part of the breast, loss of hair, and sexual
      attractiveness to a man. Spirituality was reflected as a reliance on God.
      CONCLUSIONS: Telling the story of their experience trajectory during their breast
      cancer experience is valuable in assessing African American women's feelings,
      emotions, and fears of body changes that occur during surgery and treatment.
      Their spirituality helps them through this experience. Research involving both
      African American women and their partners would provide greater insight into
      specific relationship patterns and communication related to sexuality during this
      experience. IMPLICATIONS FOR NURSING PRACTICE: Nurses need to listen to the
      stories of African American women about the initial experience of discovery,
      diagnosis, and treatment of breast cancer so they can be more informed advocates
      for these women. African American women need more information from healthcare
      providers regarding the whole experience trajectory.

PMID- 11338760
TI  - Caring demands and delay in seeking care in African American women newly
      diagnosed with breast cancer: an ethnographic, photographic study.
AB  - PURPOSE/OBJECTIVES: To describe the caring behaviors and demands of African
      American women newly diagnosed with breast cancer and to consider the influence
      of caring on the women's decision to delay prompt diagnosis and maintain
      continuing treatment. DESIGN: Focused ethnographic design using photography.
      SAMPLE/SETTING: 13 African American women (ages 30-66) purposefully selected from
      two oncology clinics in the mid-South. METHODS: Ethnographic interviews
      (transcribed verbatim), observations at informant-selected sites, field notes,
      and snapshots of caring taken by the women where caring occurred were analyzed
      using Lelninger's phases of ethnographic analysis. FINDINGS: Major themes were
      (a) generic caring for others and self as meaningful and as promoting continued
      commitment to diagnosis and treatment, (b) generic and professional caring from
      others as supportive to the women in "going on," and (c) noncaring related to a
      "wait and see" attitude of healthcare providers and of women in delaying early
      diagnosis. CONCLUSIONS: African American women's caring both for and from others
      was supportive in seeking and continuing diagnosis and treatment. The women with
      cancer viewed ensuring early diagnosis and continued treatment for other women as
      their "mission." Delay by providers and women requires further research.
      IMPLICATIONS FOR NURSING PRACTICE: Nurses must advocate assertiveness for African
      American women in seeking help for breast cancer symptoms and in challenging
      providers who adopt a "wait and see" attitude when symptoms are present. Taking
      snapshots, in addition to fostering the research process, is suggested as a
      potentially helpful intervention for women as they work through their experiences
      during treatment for breast cancer.

PMID- 11338761
TI  - The effect of aloe vera gel/mild soap versus mild soap alone in preventing skin
      reactions in patients undergoing radiation therapy.
AB  - PURPOSE/OBJECTIVES: To determine whether the use of mild soap and aloe vera gel
      versus mild soap alone would decrease the incidence of skin reactions in patients
      undergoing radiation therapy. DATA SOURCES: Prospective, randomized, blinded
      clinical trial. SETTING: Radiation therapy outpatient clinic in a cancer center
      affiliated with a major teaching medical facility. SAMPLE: The mean age of the
      participants was 56 years. The group consisted of Caucasians (74%) and African
      Americans (26%). The ethnic mix was non-Hispanic (65%) and Hispanic (35%).
      METHODS: Prophylactic skin care began on the first day of radiation therapy.
      Patients cleansed the area with mild, unscented soap. Patients randomized into
      the experimental arm of the trial were instructed to liberally apply aloe vera
      gel to the area at various intervals throughout the day. FINDINGS: At low
      cumulative dose levels < or = 2,700 cGy, no difference existed in the effect of
      adding aloe. When the cumulative dose was high (> 2,700 cGy), the median time was
      five weeks prior to any skin changes in the aloe/soap arm versus three weeks in
      the soap only arm. When the cumulative dose increases over time, there seems to
      be a protective effect of adding aloe to the soap regimen. IMPLICATIONS FOR
      NURSING PRACTICE: Skin products used to treat radiation dermatitis vary among
      institutions. Nurses should be aware that some patients may be predisposed to
      skin problems. Nurses must be aware of newly developed products and research
      regarding these products so that effective treatment can be instituted.

PMID- 11338762
TI  - Quality of life, health outcomes, and identity for patients with prostate cancer
      in five different treatment groups.
AB  - PURPOSE/OBJECTIVES: To describe how different treatments for prostate cancer
      affect health-related quality of life (QOL), health status, and masculinity.
      DESIGN: Longitudinal survey design with descriptive, correlational, and
      comparative elements. SETTING: A tertiary medical center and associated clinics
      in a suburban community in the Southwestern United States. SAMPLE: 185 men with
      localized prostate cancer were enrolled from five treatment groups: watchful
      waiting (n = 30), surgery (n = 59), conventional radiation (n = 25), proton-beam
      radiation (n = 24), and a combination of conventional radiation and proton-beam
      radiation or mixed-beam radiation (n = 47). At six months, 163 remained on the
      study; at 12 months, 154 remained: and at 18 months, 153 remained. The average
      age was 68 years, and 82% of the men were white. METHODS: Men were enrolled at
      treatment and given a questionnaire with a self-addressed, stamped envelope for
      return. Questionnaires were mailed again at 6, 12, and 18 months. MAIN RESEARCH
      VARIABLES: Health-related QOL health status, prostate treatment-specific
      symptoms, and sex-role identity. FINDINGS: No overall difference in health
      related QOL or health status was found, but post-hoc analysis revealed specific
      differences. The differences existed in sexual functioning and gastrointestinal
      treatment-specific symptoms. No relationship existed between masculinity and
      health-related QOL. CONCLUSIONS: Health-related QOL and health status are similar
      regardless of type of treatment. Radiation tends to produce more gastrointestinal
      symptoms, and surgery tends to produce more sexual functioning symptoms. Watchful
      waiting is associated with poorer general health. IMPLICATIONS FOR NURSING
      PRACTICE: Nurses can provide specific treatment-related information to men who
      are faced with making treatment decisions for prostate cancer and, in
      consultation with the healthcare team, can select a treatment best sulted to
      them.

PMID- 11338763
TI  - Depression burden, self-help interventions, and side effect experience in women
      receiving treatment for breast cancer.
AB  - PURPOSE/OBJECTIVES: To describe effects of a set of Self-Help Intervention
      Project (SHIP) interventions with self-reported depression burden on the side
      effect experience of women receiving treatment for breast cancer. DESIGN:
      Repeated measures, experimental design. SETTING: Outpatient sites at a regional
      cancer center, private practices, and health maintenance organizations. SAMPLE:
      169 women who completed data at all three data-collection points were used to
      answer the research questions. METHODS: Following random assignment, individuals
      in the treatment group participated in five different, but complementary, self
      help interventions for six weeks. The control group received the usual care.
      Variables were measured at baseline after radiation, chemotherapy, or hormone
      therapies were started to allow for the side effects to emerge at six to eight
      weeks after treatment and three months following time 2. MAIN VARIABLES:
      Depression burden, fatigue burden, pain burden, nausea burden, difficulty
      concentrating burden, anxiety burden, number of side effects, severity of side
      effects, and participation in the interventions. FINDINGS: Self-reported
      depression burden was found to significantly influence severity of side effects,
      number of side effects, and the burdens of fatigue, difficulty concentrating, and
      anxiety. Depression burden did not significantly influence the side effect
      burdens of nausea or pain. Depression burden interacted with the self-help
      interventions over time for the side effect of fatigue, but the intervention
      effect on pain burden and nausea burden was not influenced by depression burden
      over time. No significant intervention effects were found for the burden of
      difficulty concentrating or anxiety, the number of side effects, or perceived
      severity of side effects. The interventions significantly reduced the fatigue,
      pain, and nausea burden in women with breast cancer. CONCLUSIONS: The
      interventions were particularly helpful, relative to their fatigue experience,
      for women reporting a high level of depression burden. Findings also contribute
      to conceptual clarification of essential aspects of the side effect experience
      and provide a basis for measure and intervention refinement. IMPLICATIONS FOR
      NURSING PRACTICE: Every woman who is undergoing cancer treatment should be
      assessed for depression and depression burden. Self-help interventions are
      effective and convenient treatments that reduce side effects and promote quality
      of life in women with breast cancer.

PMID- 11338764
TI  - [Therapy of osteoarthritis--from controlling the symptoms to preserving articular
      cartilage].
AB  - An overview of pharmacological and surgical approaches aiming to preserve the
      articular cartilage and prevent progression of degeneration during osteoarthrosis
      (OA) is given. From the pharmacological approaches the most promising appears to
      be glucosaminosulphate from the SYSADOA group. Also preparations affecting the
      bone metabolism as calcitonin and biosulphates are tested. Along with it some
      biological curatives blocking the activity of IL-1, TNF-alpha, MMP, and NO are
      experimentally used. They have been parenterally administered, however, the gene
      therapy enabling transfer of the genetic information by means of retroviruses
      directly into the joint and synthesis of the target proteins in situ becomes
      clinically tested. From the surgical approaches aimed to preserve the articular
      cartilage several methods are currently tested: joint debridment, transplantation
      of the soft components, transplantation of the cartilage grafts and some
      experimental methods.

PMID- 11338765
TI  - [Laser trabeculoplasty--present and future perspectives].
AB  - Laser trabeculoplasty has been used in the treatment of various types of glaucoma
      for nearly 20 years. It's intraocular pressure lowering effect through
      enhancement of aqueous outflow is well documented. In spite of this, the precise
      effect of laser trabeculoplasty in the trabecular meshwork is only partially
      understood. It is related to laser wave length, laser power, burns location,
      number of shots etc. The effectiveness of laser trabeculoplasty diminishes over
      time, but can be renewed with re-treatment. Laser trabeculoplasty has connected
      with minimum complications and it is most effective in patients with primary open
      angle glaucoma, pigmentary glaucoma and the exfoliation syndrome glaucoma, though
      the long-term results of this microsurgery laser treatment are not quite
      indisputable.

PMID- 11338766
TI  - [Occurrence of reflux esophagitis in patients with chest pain and a normal
      selective coronary angiogram].
AB  - BACKGROUND: Chest pains are related to coronary disease, and to several other
      disorders, among which the most commons are the oesophageal diseases. The aim of
      the work was the identification of the reflux oesophagitis in patients with chest
      pain and normal selective coronary angiogram. METHODS AND RESULTS: In the
      examined group 65 patients (42 females, 23 males) of the average age 55.2 years
      were included. All of them underwent endoscopic investigation with biopsy from
      the terminal part of the oesophagus. Endoscopy picture was evaluated according
      Savary-Miller classification. Biopsy samples were histologically examined and
      evaluated according our proper classification of the reflux oesophagitis (1st
      degree: mild, 2nd degree: medium, 3rd degree: heavy, 4th degree: ulcerous).
      Endoscopical finding was normal in 59 patients (90.8%), reflux oesophagitis of
      the 1st degree in 2 patients (3.1%) 2nd degree in one patient (1.5%), 3rd degree
      in 2 patients (3.1%), 4th degree in one patient (1.5%). Histological changes
      which can be included into the picture of so called microscopic oesophagitis were
      found in 49 patients (75.4%). The rest of patients had the histology picture
      normal. CONCLUSION: In 75.4% of patients with chest pain and negative selective
      coronary angiogram histological examination revealed structural changes
      corresponding with oesophagitis, mostly of the mild type.

PMID- 11338767
TI  - [Clinical picture of homocystinuria with cystathionine beta-synthase deficiency
      in 19 Czech and Slovak patients].
AB  - BACKGROUND: Homocystinuria due to cystathionine beta-synthase deficiency is an
      autosomal recessive disorder of methionine metabolism. It manifests with
      vascular, central nervous system and connective tissue disturbances, and
      phenotypically resembles Marfan's syndrome. We analysed the clinical course of
      homocystinuria in Czech and Slovak patients. METHODS AND RESULTS: The group of
      homocystinuric patients consisted of 19 individuals (12 males and 7 females) aged
      5-32 years (average age 18 years), who were diagnosed between 1980 and 1999. The
      overall incidence of homocystinuria in the Czech and Slovak Republics was
      1:287,000. The proportion of pyridoxine-responsive patients was 47%. The average
      follow-up period was 10 years (range 1 month to 19 years). The prevalence of the
      individual signs in the group was as follows: lens dislocation--95% of patients,
      progressive myopia--79%, marfanoid habitus--74%, kyfoscoliosis--68%, osteoporosis
      -63%, psychomotor retardation--58%, other neurologic symptomatology--58% and
      tromboembolism--21%. The average delay between the first sign of the disease and
      the time when the diagnosis was made was 4 years (range 1 to 14 years). At the
      time of diagnosis the average levels of metabolites in plasma were as follows:
      total homocysteine 348 mumol/l (range 211-536), free homocystine 70 mumol/l
      (range 0-203) and methionine 359 mumol/l (range 75-937). CONCLUSIONS: Both the
      clinical course of homocystinuria due to the cystathionine beta-synthase
      deficiency and its incidence in the Czech and Slovak Republics are similar to
      those in other populations. Since homocystinuria is a treatable disease, it
      should be included in the differential diagnosis of Marfan's syndrome,
      tromboembolism and severe psychomotor retardation.

PMID- 11338769
TI  - [Headaches, modern classification, diagnosis and therapy].

PMID- 11338768
TI  - [Normal pressure hydrocephalus--a rare late complication of radiography of the
      spine using contrast media].
AB  - The aim of the study is to inform professionals about a serious complication--the
      liquor malabsorption--developing in relation to the routinely performed roentgen
      contrastive examination (PMG). It also demonstrates advantages of the lumbal
      infusion test (LIT) as a part of the algorithm of the shunt operation in patients
      with supposed pathology of liquor malabsorption.

PMID- 11338771
TI  - Spectrophotometric determination of manidipine dihydrochloride based on formation
      of charge-transfer complex with iodine.
AB  - A new spectrophotometric method for determining manidipine dihydrochloride has
      been developed. The method was based on the formation of charge transfer complex
      between this drug as n-donor and iodine the s-acceptor. The iodine was found to
      form charge-transfer complex in a 1:1 stoichiometry with absorption bands at 290
      and 353 nm. Conformity to Beer's law enabled the assay of dosage forms of this
      drug, the concentration range for the best accuracy is 3-11 micrograms/ml. The
      method can be applied successfully to the analysis of commercially available
      manidipine dihydrochloride tablets.

PMID- 11338772
TI  - Cissus stem gum as potential dispersant in pharmaceutical liquid systems:
      rheological characterization.
AB  - A Co-axial viscometer, the Haake-Rotovisco, was used studying the rheological
      behaviour of aqueous dispersion of cissus stem gum. At concentrations of 4% w/v
      and above, the mucilage is both pseudoplastic and thixotropic. Two equations
      derived from a power law expression for apparent viscosity(h): h = ekc + b were
      solved simultaneously (c = 4 and 8% w/v) in the determination of material
      constants k and b for cissus gum. The apparent viscosity of the polymeric liquid
      system was affected by concentration of the gum, pH, temperature and aging.

PMID- 11338773
TI  - Computer supported studies on design and evaluation of solid dispersions of
      carbamazepine.
AB  - The main advantages of solid dispersions (the drug could be maintained in a
      bioavailable form, dosage reduction and cleaner manufacturing conditions) provide
      scope for the continued interest in field. Additionally, their use in providing a
      sustained or controlled release of drugs has only been tentatively examined. In
      the present study, Carbamazepine has been used to develop a dosage form which
      will provide a booster amount followed by sustained release of the drug for
      effective control of epileptic seizures while keeping the serum level of the drug
      at minimum. Enteric polymers CAP and CAT have been used to retard the release
      till the formulation reaches the intestine. Either individually or combined
      fractions of the formulations may be used in the therapy of epilepsy.

PMID- 11338774
TI  - Design and evaluation of microcapsules of diltiazem hydrochloride.
AB  - Diltiazem Hydrochloride (DTZ.HCl), a potent calcium channel blocker was
      microencapsulated by emulsion/solvent evaporation technique using non-aqueous
      solution of Ethylcellulose (EC) polymer to achieve its release from microcapsules
      at a slower rate. At the optimal conditions of process variables such as stirring
      speed, temperature of the medium, drug-polymer ratio, maximum encapsulation
      efficiency was obtained and the microcapsules produced were free flowing,
      discrete and spherical as evident from Scanning Electron Microscopy. The in vitro
      release experiments were carried out in the simulated gastric fluid (pH 1.2) and
      simulated intestinal fluid (pH 7.2 phosphate buffer) using USP XXII apparatus II.
      The data obtained from the dissolution profiles were compared in the light of
      different kinetic models and the regression coefficients were compared.

PMID- 11338775
TI  - A comparative study of modified starches in direct compression of a poorly water
      soluble drug (hydrochlorothiazide).
AB  - The direct compression properties of four modified starches in
      hydrochlorothiazide (HCTZ) tablets were studied. The starches were obtained
      locally from common plant sources and were modified through physicochemical
      treatment. Each modified starch was used as the only filler-binder-disintegrant
      in the formulation of hydrochlorothiazide tablets containing 25 mg of the drug.
      The tablets were produced by the direct compression technology. Sta-Rx 1500, a
      directly compressible starch, was used as basis for comparison. Evaluated tablet
      properties included weight and drug content uniformity, hardness and friability
      as well as disintegration time and dissolution profile. The modified starches
      exhibited species specificity in terms of the tablet properties. The weight, drug
      content and disintegration time for all batches of tablets were within acceptable
      limits. Proper ranking of the starches on the basis of specific tablet properties
      was used to highlight their differences.

PMID- 11338776
TI  - Is uranyl scavenger hexakis(3,6-anhydro) tetrakis(2A,B,D,E-O-octyl)
      cyclomaltohexaose (OCT) relevant with biosystems?
AB  - Hexakis(3,6-anhydro)tetrakis(2A,B,D,E-O-octyl) cyclomatohexaose (OCT) has been
      recently shown as a powerful cryptant for lead, mercury, and especially for
      uranyl. As previous results have been obtained in an organic solvent (methanol),
      a similar evaluation of OCT complex formation was achieved in aqueous medium and
      in the presence of membrane-mimicking systems such as phospholipid vesicles,
      liposomes and micelles. It was found that OCT, while completely insoluble in
      water, forms solid gel structures when in equimolar mixtures of water and
      methanol. Moreover, OCT exhibits detergent properties. Finally, OCT was
      successfully introduced in detergent solutions while keeping. Uranyl complexing
      properties. Possible applications of such models were also discussed.

PMID- 11338777
TI  - Evaluation of the physico-chemical properties of a new polysaccharide gum from
      Prosopis africana.
AB  - The gum obtained from the ripe seeds of Prosopis africana was processed to
      compendial standard for plant gums and characterised. Toxicological studies of
      the polysaccharide on mice showed the material to be safe. The material hydrates
      slowly in aqueous media to form a colloidal dispersion. Swelling studies on the
      gum shows that the gum has a higher swelling capacity than methylcellulose.
      Rheological studies showed that the material is more viscous than tragacanth gum
      at equivalent concentrations. Acid hydrolysis and thin layer chromatography of
      the resulting hydrolysates showed that the gum contains glucose, fructose,
      galactose and xylose as the monosaccharide components. Microbial tests showed the
      gum to contain 8.26 x 10(4) viable cells per gram when freshly prepared. Other
      properties of the gum evaluated includes; melting or charring temperature,
      optical properties, true density, ash values, element content as well as its
      reactions with lead subacetate solution and 0.02 M iodine.

PMID- 11338778
TI  - Behaviour of 2-substituted 1,3-indandiones towards aldimines.
AB  - Treatment of 2-cyano-1,3-indandione (1) with aldimines gave the expected Mannich
      bases (2-4), while the arylidenes (7,8) were obtained when 2-ethoxycarbonyl-1,3
      indandione (5) was subjected to react with aldimines. On the other hand,
      treatment of 2-acetyl-1,3-indandione (9) with aldimines gave compounds
      (11,12,14). The reaction of 2-phenyl-1,3-indandione (15) with aldimines gave the
      arylamino and the ethylene diamino derivatives (17, 18). Pictet Spengler reaction
      of 19b gave the spiro compound (21).

PMID- 11338779
TI  - Biologically active substituted benzodiazepines and their effect on
      cardiovascular and central nervous system.
AB  - Some substituted 1,5-benzodiazepine derivatives (including a spirocyclopentane
      moiety) were synthesized (Table I) and evaluated for their hypotensive and CNS
      activities respectively. The compounds which showed promising cardiovascular
      activity also exhibited marked anti-depressant action (Table II,III,IV). All the
      compounds showed higher ALD50 value.

PMID- 11338780
TI  - 1H-NMR study of heavy metals complexation with hexakis(3,6-anhydro)
      tetrakis(2A,B,D,E-O-octyl) cyclomaltohexaose (OCT).
AB  - The selection of the cations bound by hexakis (3,6-anhydro) tetrakis (2A,B,D,E-O
      octyl) cyclomatohexaose (OCT) was performed by thin layer chromatography. The
      three cations selected, UO(2)2+, Pb2+ and Hg2+ were then studied by 1H-NMR. A 2:1
      OCT/cation stoichiometry was identified in the cases of UO(2)2+ and Pb2+. While
      UO(2)2+ binding (logK around 6) followed a fast exchange kinetics, a slow or
      intermediate complexation was found with Pb2+ (logK = 5.6) and Pb2+,
      respectively. In the latter case, the poor solubility of Hg2+ precluded to
      propose neither a stoichiometry nor an estimation of the affinity constant.

PMID- 11338781
TI  - [Image of the month. Orthostatic hypotension filmed by Finapres: autonomic
      neuropathy versus iatrogenic cause].

PMID- 11338782
TI  - [Pharmacy clinics. How I treat...Osteoarthritis. 2nd part: new therapeutic
      perspectives].
AB  - Besides the management of symptoms of osteoarthritis, a lot of interest was
      raised for molecules aiming at slowing down the structural progression of the
      disease. This paper summarizes the currently available data allowing to discuss
      the efficacy and tolerance of these chemical entities.

PMID- 11338783
TI  - [Clinical case of the month. Complete replacement of the ascending aorta and
      aortic arch in a case of chronic aortic dissection].
AB  - We report the case of a patient who developed an evolutive chronic aortic
      dissection after ascending aorta replacement for acute type A aortic dissection.
      Owing to the development of severe aortic regurgitation, aortic root
      pseudoaneurysm and aneurysmal dilatation of the arch and descending aorta,
      reoperation was adviced. Reoperation included Cabrol modification of the Bentall
      operation and aortic arch replacement with elephant trunk performed under deep
      hypothermic circulatory arrest. The incidence of late aneurysmal formation in
      type 1 aortic dissection has been reported to be 30%. Close postoperative follow
      up of the aortic diameter is necessary to detect a critical dilatation and to
      permit elective reoperation.

PMID- 11338784
TI  - [Percutaneous vertebroplasty].
AB  - Percutaneous vertebroplasty consists in the injection of acrylic cement under
      fluoroscopic control into a vertebral body presenting with destabilizing and
      painful lesion such as vertebral haemangioma, osteoporotic vertebral crush
      syndrome and malignant tumors. Owing to the strong analgesic effect following the
      vertebral stabilization, this method represents the procedure of choice for the
      treatment of this kind of lesions.

PMID- 11338785
TI  - [Emergency practice: specifics in the management of complex multiple trauma].
AB  - Almost twenty years ago, Trunkey showed that deaths due to trauma followed a
      trimodal distribution over time. Half of these deaths were delayed by at least
      one to two hours after the initiating insult. This interval (the "golden hour")
      can be exploited, especially in specialized trauma centers (where the most
      severely injured patients are cared for), to aggressively treat these patients,
      thereby reducing morbidity and mortality. In Belgium, this hierarchy of trauma
      care centers is non-existent; patients are distributed within the healthcare
      system randomly, depending on the localisation of the accident and the directives
      of the unified "100" call centre. Because this limits the number of cases any one
      centre treats, this type of arrangement acts to inhibit the acquisition of
      competency in the handling of these complex patients. The relative lack of
      experience of individual emergency departments leads to difficulties in
      establishing diagnostic and treatment priorities for the most severely injured
      trauma victims. The approach to these patients must follow very precise
      guidelines, established scientifically in order to minimize the impact of the
      injury on life and maximize chances of satisfactory functional recovery. In this
      paper, we describe the general principles of the initial approach to victims of
      complex multiple trauma.

PMID- 11338787
TI  - [Recent progress in the pharmacology of hypnotics and anxiolytics].
AB  - Recent studies on the respective contribution of GABAA receptor subunits in the
      various pharmacological effects of benzodiazepines suggest that the sedative and
      amnesic properties of diazepam are mediated by enhancement of gabaergic
      transmission in neurons expressing the alpha 1 subunit while the anxiolytic
      effect is selectively mediated by alpha 2 subunit. These findings suggest that a
      separation of the pharmacological properties of benzodiazepines is possible and
      that drugs with increased clinical specificity could be developed.

PMID- 11338786
TI  - [Shoshin beriberi: myth or reality?].
AB  - Shoshin is a fulminating form of cardiac beriberi developing in a few hours in a
      young alcoholic. Without specific treatment it evulers, toward death by
      cardiogenic shock and metabolic acidosis. Treatment by thiamine and
      alkalinisation permits a spectacular and fast recovery.

PMID- 11338788
TI  - [Latex allergy -- when uncertainty remains the only certainty].
AB  - Latex devices release allergenic proteins which are responsible for immune IgE
      mediated reactions. Casual surgical gloves are most often responsible for contact
      urticaria. Other allergic manifestations include conjunctivitis, rhinitis,
      asthmatiform dyspnoea and diverse gastro-intestinal troubles. Cardiovascular
      collapse and anaphylactic shock are possible. Physicians and the paramedical
      staff are particularly affected by the allergy to latex proteins. Multi-operated
      patients and those under prolonged health care using latex-made medical probes
      also present a high-risk group for this type of allergy.

PMID- 11338789
TI  - [Egg-cell complex, molecular embryology, human genome, then, human proteome].

PMID- 11338790
TI  - [The egg-cell of Edouard Van Beneden and molecular embryology].
AB  - Embryology started in the XIXe eeuw as a morphological study. Edouard Van Beneden
      contributed largely to its development through his works on the female sexual
      cell and on the development of the tunicates. But since 1985 the new era of
      molecular embryology is opening. Large therapeutic applications will be available
      in the near feature.

PMID- 11338791
TI  - [How I investigate...difficult cases of tuberculous meningitis].
AB  - To formally document the presence of the bacillus of Koch in meninges still
      remains difficult and depends on many variables. We report two cases where the
      diagnosis proved difficult. The presentation of tuberculous meningitis can take
      several aspects. Mantoux reaction is frequently negative. The BK cultures, which
      demonstrate the diagnosis, depend on the volume of CSF and on the importance of
      BK dissemination. It, unfortunately, remains difficult to make the diagnosis of
      tuberculous meningitis even though this pathology can have extremely deleterious
      consequences.

PMID- 11338792
TI  - [Pharmacy clinics. Medication of the month. Clopidogrel (Plavix)].
AB  - Clopidogrel is launched in Belgium by Sanofi-Synthelabo and Bristol-Myers Squibb
      under the trade name of Plavix. It is a potent and irreversible ADP receptor
      antagonist that proved to be more effective than aspirin as antiplatelet agent in
      the multicentre, randomised double-blind CAPRIE study. It is indicated, at a
      dosage of 75 mg/day, for the reduction of atherosclerotic events including
      myocardial infarction, ischaemic stroke and vascular death in patients with
      atherosclerosis manifested by recent stroke, myocardial infarction or established
      peripheral vascular disease. Furthermore, recent studies demonstrated that the
      combination of clopidogrel with aspirin is more effective than aspirin alone and
      better tolerated than the combination ticlopidine-aspirin for the prevention of
      atherothrombosis after placement of intravascular stents. Ongoing trials are
      evaluating the efficacy and safety of such clopidogrel-aspirin combination after
      acute ischaemic coronary events or in patients at very high risk of stroke. Thus
      the indications of clopidogrel may become even larger in a next future.

PMID- 11338793
TI  - Orthopaedic measurements with computed radiography. Methodological development,
      accuracy, and radiation dose with special reference to the weight-bearing lower
      extremity and the dislocating patella.
AB  - The overall aim of this study was to develop and evaluate a measurement system
      for computed radiography (CR) and Picture Archiving and Communication Systems
      (PACS), permitting measurements of long distances and angles in and between
      related images. The developed measurement system, which was based on the QUESTOR
      Precision Radiography (QPR) system, was applied to the weight-bearing knee with
      special reference to the dislocating patella. The QPR system modified for CR
      fulfilled the criteria for measuring the weight-bearing knee. The special
      measuring assistance tools that were developed were important for the
      implementation of CR and PACS, particularly in workstations programmed for
      musculoskeletal radiology. The energy imparted to the patient was reduced by 98%
      at the lowest exposure of the CR-system, compared with our conventional analogue
      method, without loss of diagnostic accuracy. The CR technique creates a
      possibility, to an extent not previously feasible, to differentiate the exposure
      parametres (and thus minimise the radiation dose to the patient) by carefully
      considering the purpose of the examination. A radiographic method for measuring
      the rotation of the femur and the tibia, the Q-angle, and the patellar
      translation was developed and applied to healthy volunteers. The introduced
      patellar variables have yielded new insights into the complex sequence of motions
      between the femur, tibia, and patella. The patients with a dislocating patella
      were subdivided into one "clean" group of spontaneous dislocations and one group
      with various traumas in the history, which thus resulted in two groups with
      distinct radiographic differences. The Q-angle was decreased in knees that had
      suffered dislocations, and the traditional surgical treatment with a further
      reduction of the Q-angle must be challenged. The use of clinical measurements of
      the Q-angle was not an optimal way to evaluate the mechanical alignment in the
      patellofemoral joint under physiological conditions. In this study, we have
      proved that the developed method for CR and PACS is a useful technique for
      measurements in and between related images, and is superior to the conventional
      analogue technique.

PMID- 11338794
TI  - Maternity leave for adoptive parents in Ontario.

PMID- 11338795
TI  - Diabetes in Canada's First Nations.

PMID- 11338796
TI  - Diabetes in Canada's First Nations.

PMID- 11338797
TI  - Reducing the rates of inappropriate labour induction.

PMID- 11338798
TI  - Waiting time for breast cancer surgery in Quebec.
AB  - BACKGROUND: Currently there is no agreement on the optimal time to treatment of
      breast cancer; however, given the considerable emphasis on early detection, one
      would expect a similar emphasis on early treatment. The purpose of our study was
      to assess the time interval to surgery from initiation of diagnosis among Quebec
      women with breast cancer and to examine the influence on waiting time of age,
      pattern of care and cancer stage. METHODS: Records of physician fee-for-service
      claims and of hospital admissions were obtained for all Quebec women who
      underwent an invasive procedure for the diagnosis or treatment of breast cancer
      between 1992 and 1998. Waiting time was calculated as the number of days between
      the first diagnostic procedure and surgical treatment. RESULTS: There were 29,606
      episodes of breast cancer surgery among 28,100 women: 5922 mastectomies and
      23,684 lumpectomies. The absolute number of episodes of breast cancer treated
      with surgery rose from 3626 in 1992 to 5162 in 1998. The overall median waiting
      time was 34 days (interquartile range [IQR] 19-62); 13.5% of the women waited
      longer than 90 days. The median waiting time rose from 29 days (IQR 15-54) in
      1992 to 42 days (IQR 24-72) in 1998, representing a relative increase of 37% (95%
      confidence interval [CI] 32%-43%) after adjusting for age and cancer stage. The
      median waiting time increased with the number of diagnostic procedures, from 24
      days (IQR 14-42) with 1 procedure to 48 days (IQR 27-84) with 3 procedures to 72
      days (IQR 43-121) with 4 procedures, representing adjusted relative increases of
      97% (95% CI 91%-103%) and 194% (95% CI 181%-208%), respectively. The proportion
      of women receiving 3 or more diagnostic procedures before surgery increased
      steadily over the study period, from 19.2% in 1992 to 33.0% in 1998. The median
      waiting time was shorter with more advanced stages of cancer: 53 days (IQR 30-86)
      for carcinoma in situ, 35 (IQR 20-62) for localized disease, 28 (IQR 16-49) for
      regional disease and 24 (IQR 11-52) for disseminated disease. INTERPRETATION:
      Waiting time between initial diagnosis and first surgery for breast cancer has
      increased substantially in Quebec between 1992 and 1998. Possible explanations
      include increased demand, decreased resources and changes in patterns of care.

PMID- 11338799
TI  - Evaluation of a decision aid for patients considering autologous blood donation
      before open-heart surgery.
AB  - BACKGROUND: Patients undergoing open-heart surgery frequently require one or more
      blood transfusions. Because of the risks of receiving blood from volunteer
      donors, some patients choose to donate their own blood before surgery. This
      reduces their risk of exposure to volunteer-donated blood, but it increases their
      chance of receiving any transfusion, either of self-donated or volunteer-donated
      blood. Also, preoperative hemoglobin levels tend to be lower in patients who
      donate their own blood, and surgeons may be more likely to give transfusions to
      patients with self-donated blood. To help patients decide whether to donate their
      blood before surgery, we designed a decision aid comprising a booklet and
      audiotape and assessed its effectiveness. METHODS: The 59 study subjects were a
      sample of consecutive patients referred to the Ottawa Heart Institute between
      Oct. 1, 1998, and Jan. 5, 1999, for future coronary artery bypass grafting, valve
      surgery or combined surgery. All were eligible to donate blood. Initial
      questionnaires were administered in the clinic by a physician or study nurse, and
      follow-up questionnaires were completed at home and mailed in after use of the
      decision aid. Outcome measures included patients' knowledge, values (importance
      ratings), preferences for transfusion methods, decisional conflict (the amount of
      uncertainty about the course of action to take), risk perception and
      acceptability of the decision aid. RESULTS: Mean knowledge scores on a 15-item
      test increased from 67% correct responses before the decision aid to 85% correct
      responses after use of the aid (p < 0.001); the effect was similar when the
      patients were divided into subgroups according to education level. The number of
      patients favouring donating their own blood increased from 41 (69%) before to 45
      (76%) after use of the aid. Nine (64%) of 14 initially uncertain patients
      preferred autologous donation after use of the aid. The overall mean score for
      decisional conflict was unchanged, at 1.7, which indicated a low level of
      uncertainty. Risk perception improved, from 0%-14% correct responses on an 8-item
      test before the aid to 18%-60% correct responses after use of the aid. The
      decision aid was acceptable to the majority of patients, and 95% indicated that
      they would recommend it to others. INTERPRETATION: The decision aid improved
      knowledge and risk perceptions of blood donation and transfusion, and it helped
      uncertain patients to make choices.

PMID- 11338800
TI  - Low rate of adequate folic acid supplementation in well-educated women of high
      socioeconomic status attending a genetics clinic.

PMID- 11338801
TI  - Cervical cancer: the increasing incidence of adenocarcinoma and adenosquamous
      carcinoma in younger women.

PMID- 11338802
TI  - The revised CONSORT statement: honing the cutting edge of the randomized
      controlled trial.

PMID- 11338803
TI  - The rich-poor gap in global health research: challenges for Canada.

PMID- 11338804
TI  - Bioethics for clinicians: 25. Teaching bioethics in the clinical setting.
AB  - Bioethics is now taught in every Canadian medical school. Canada needs a cadre of
      teachers who can help clinicians learn bioethics. Our purpose is to encourage
      clinician teachers to accept this important responsibility and to provide
      practical advice about teaching bioethics to clinicians as an integral part of
      good clinical medicine. We use 5 questions to focus the discussion: Why should I
      teach? What should I teach? How should I teach? How should I evaluate? How should
      I learn?

PMID- 11338805
TI  - Problems for clinical judgement: 3. Thinking clearly in an emergency.
AB  - The resuscitation of a patient in extremis is frequently characterized by chaos
      and disorganization, and is one of the most stressful situations in medicine. We
      reviewed selected studies from the fields of anesthesia, emergency medicine and
      critical care that address the process of responding to a critically ill patient.
      Individual clinicians can improve their performance by increased exposure to
      emergencies during training and by the incorporation of teamwork, communication
      and crisis resource management principles into existing critical care courses.
      Team performance may be enhanced by assessing personality factors when selecting
      personnel for high-stress areas, explicit assignment of roles, ensuring a common
      "culture" in the team and routine debriefings. Over-reliance on technology and
      instinct at the expense of systematic responses should be avoided. Better
      training and teamwork may allow for clearer thinking in emergencies, so that
      knowledge can be translated into effective action and better patient outcomes.

PMID- 11338806
TI  - The Manitoba Cataract Waiting List Program.
AB  - This article describes the Manitoba Cataract Waiting List Program. This program
      uses a centralized database to track and prioritize all patients waiting for
      cataract surgery. It provides an objective and reliable measure of the length of
      the wait, and patients on the waiting list are treated in a more equitable
      fashion through application of a uniform method of prioritization. The program
      will allow for long-term tracking of quality of care through monitoring of the
      average length of wait for patients with comparable functional impairment. It
      will also allow for long-term monitoring of thresholds for surgery. It has
      brought to light previously undocumented issues, such as the simultaneous booking
      of both eyes for cataract surgery and variations in waiting time between
      surgeons.

PMID- 11338807
TI  - Rheumatology: 12. Pain in the neck.

PMID- 11338808
TI  - Family medicine loses lustre as students "vote with feet" in 2001 residency
      match.

PMID- 11338809
TI  - Chinese medicine now part of primary care scene in BC.

PMID- 11338810
TI  - US health system needs major overhaul: academy.

PMID- 11338811
TI  - Nfld., Sask. retain smallest proportion of postgraduate trainees.

PMID- 11338812
TI  - One-quarter of South African adults now HIV positive.

PMID- 11338813
TI  - Hospital moves to assure public that autopsies are respectful, legal.

PMID- 11338814
TI  - [Experience in organization of military polyclinics in frame of medical insurance
      system: providing paid medical services].

PMID- 11338815
TI  - [Liquidation of medical and sanitary consequences of flood].

PMID- 11338816
TI  - [Characteristics of oral cavity hygiene in children from garrisons and military
      cantonments].

PMID- 11338817
TI  - [Cytamines--preparations for maintaining high professional ability and longevity
      in servicemen].

PMID- 11338818
TI  - [Rendering emergency surgical aid in gunshot penetrating thoracic wounds].
AB  - In modern limited military conflicts the gunshot penetrating wounds of breast
      (GPWB) are the most severe type of fighting trauma with high lethality on field
      and development of complications. Today the main method of treatment in GPWB is
      low-invasive intervention--thoracocentesis and drainage of pleural cavity. In
      stationary conditions it is reasonable to conduct the active drainage of pleural
      cavity with the help of vacuum-aspirators and during evacuation of casualties to
      use the devices for drainage of pleural cavity with petalled valve. In GPWB to
      provide rendering of surgical service in time it is necessary to equip hospitals
      with home-produced equipment and apparatus according to achievements thoracic
      surgery as well as training of military field surgeons.

PMID- 11338819
TI  - [Traction trauma of peripheral nerves].

PMID- 11338820
TI  - [Hospital-substitutive technologies--grounds for reforming therapeutic and
      diagnostic base of the military health system].

PMID- 11338821
TI  - [Local cellular and humoral immunity in patients with acute bronchitis].
AB  - Complex investigation of some factors of local immunity in acute bronchitis (AB)
      was conducted in order to determine the mechanisms of formation of
      immunodeficient states in respiratory system and their influence on disease
      course. Study of cellular link of pulmonary local defense (PLD) included
      investigation of total number of cells in bronchoalveolar lavage fluid (BALF),
      their viability, alveolar macrophages (AM), neutrophils, lymphocytes (T- and B-
      lymphocytes), phagocytic index and phagocytic number of AM and neutrophils,
      receptor system of AM and neutrophils. Examination of PLD humoral factors in BALF
      in the patients with AB consisted of determination of IgA, IgM, IgG and lysocin
      contents. The data obtained shows the dependence of state of local cellular and
      humoral immunity on AB clinical-and-etiologic form. The most expressed degree of
      cellular and humoral immunodeficiency is caused by staphylococcal infection. The
      role of dysfunction of cellular and humoral link of pulmonary immune defense in
      bronchoobstructive syndrome genesis was established. Restoration of cellular and
      humoral immunity indices in convalescents with AB lags behind the time of
      clinical recovery. The significant degree of immunodeficiency in the patients
      with AB lingering form can be a pathogenetic factor in chronization of
      inflammatory process in lungs.

PMID- 11338822
TI  - [Odeston in treatment of chronic diseases of hepatobiliary system].

PMID- 11338823
TI  - [Onychomycosis therapy].

PMID- 11338824
TI  - [Evaluation of the functional state and working capacity of patients with chronic
      toxoplasmosis].
AB  - Operator's main functions were studied in 78 patients with chronic toxoplasmosis
      during the period of disease aggravation and during the following 6 months. It
      was revealed that marked disorders in higher nervous activity and psychomotor
      system are observed in the patients during the period of aggravation,
      significantly more expressed during disease recurring course. It is reasonable to
      examine servicemen with chronic toxoplasmosis using psychologic and
      psychophysiologic methods before treatment and in 6 months after its completion.
      Without clear tendency towards improvement of professionally significant
      qualities in 6 months after treatment (level of neurotization, psychopathyzation,
      comparative number of mistakes in attention test and during reckon in head,
      delayed memory, positive tapping-test) it is not recommended to use servicemen at
      the posts having operator's profile and connected with long staying in secluded
      small collectives.

PMID- 11338825
TI  - [Medical ground for the system providing safe flights on the modern aircraft].

PMID- 11338826
TI  - [Effect of certain environmental factors on Bradyrhizobium japonicum].
AB  - Dependence of motility and chemotaxis was studied in two strains of
      Bradyrhizobium japonicum upon several environmental factors. In both strains,
      chemotaxis was found to increase with an increasing concentration of the
      attractant (glucose) to 5.6 x 10(-2) M. Both motility and chemotaxis reached
      their maximum in the two- to three-day cultures at neutral pH. The maximum
      motility of these bacteria occurred at 40 degrees C. The maximum values of
      chemotaxis in these microorganisms were, however, observed at 20-25 degrees C.
      Chemotaxis in acidic or alkaline media and at low temperatures was found to be
      markedly weaker. Nonoptimal values of these parameters in soil may be a limiting
      factor for the interaction of the given bacteria with soybean roots.

PMID- 11338827
TI  - [Effect of oil on the size of number, biomass, and viability of fungi in highmoor
      peats].
AB  - Some microbiological parameters, such as the fungal mycelium length, the number
      of fungal spores, the distribution profiles of micromycetes, the viability of
      fungal propagules, the length distribution of micromycete hyphae, and the
      proportion between fungal spores and yeastlike cells, can be used to determine
      the degree of soil contamination with oil and the concentration that is
      inhibitory to the micromycete complexes of highmoor peats.

PMID- 11338828
TI  - [Microbiological processes in a high-temperature oil field].
AB  - Thermophilic sulfate-reducing bacteria (SRB) oxidizing lactate, butyrate, and C12
      C16 n-alkanes of oil at a temperature of 90 degrees C were isolated from samples
      of water and oil originating from oil reservoirs of the White Tiger high
      temperature oil field (Vietnam). At the same time, no thermophiles were detected
      in the injected seawater, which contained mesophilic microorganisms and was the
      site of low-temperature processes of sulfate reduction and methanogenesis.
      Thermophilic SRB were also found in samples of liquid taken from various
      engineering reservoirs used for oil storage, treatment, and transportation. These
      samples also contained mesophilic SRB, methanogens, aerobic oil-oxidizing
      bacteria, and heterotrophs. Rates of bacterial production of hydrogen sulfide
      varied from 0.11-2069.63 at 30 degrees C and from 1.18-173.86 at 70 degrees C
      micrograms S/(1 day); and those of methane production, varied from 58.4-100 629.8
      nl CH4/(1 day) (at 30 degrees C). The sulfur isotopic compositions of sulfates
      contained in reservoir waters and of hydrogen sulfide of the accompanying gas
      indicate that bacterial sulfate reduction might be effective in the depth of the
      oil field.

PMID- 11338829
TI  - [Features of cyanobacterial-bacterial complexes of microsymbionts of plant
      syncyanoses].
AB  - The morphology and ultrastructure of associative microsymbiont complexes (AMC)
      isolated from the ferns Azolla pinnata and Azolla sp. and the apogeotropic roots
      of the cycad Cycas revoluta were studied. The composition of the AMC obtained
      includes the cyanobionts (symbiotic cyanobacteria) and satellite bacteria (SB).
      It was found that two types of cyanobacteria that substantially differ in their
      morphological organization are likely present as cyanobionts in the coralloids of
      C. revoluta. The isolated cyanobiont strains exhibited the morphological traits
      and regularities of development typical of the genus Nostoc; they were
      characterized by the ability of their cells to divide in mutually perpendicular
      planes. When isolating AMC from different morphological zones of C. revoluta
      apogeotropic roots, SB growth was revealed only around the pieces corresponding
      to the coralloid apical zone. No AMC components were revealed around the segments
      of the basal growth zone. Pure cyanobiont cultures were obtained from the AMC of
      C. revoluta coralloids. The AMC isolated from the ferns A. pinnata and Azolla sp.
      are characterized by obligate mutual dependence of the partners (the cyanobiont
      and SB).

PMID- 11338830
TI  - [A new family of Alteromonadaceae fam. nov., including the marine proteobacteria
      species Alteromonas, Pseudoalteromonas, Idiomarina i Colwellia].
AB  - The taxonomic position of the marine genera Alteromonas, Pseudoalteromonas,
      Idiomarina, and Colwellia within the gamma subclass of the class Proteobacteria
      were specified on the basis of their phenotypic, genotypic, and phylogenetic
      characteristics. Gram-negative aerobic bacteria of the genera Alteromonas,
      Pseudoalteromonas, and Idiomarina and facultatively anaerobic bacteria of the
      genus Colwellia were found to form a phylogenetic cluster with a 16S rRNA
      sequence homology of 90% or higher. The characteristics of these genera presented
      in this paper allow their reliable taxonomic identification. Based on the
      analysis of our experimental data and analyses available in the literature, we
      propose to combine the genera Alteromonas, Pseudoalteromonas, Idiomarina, and
      Colwellia into a new family, Alteromonadaceae fam. nov., with the type genus
      Alteromonas.

PMID- 11338831
TI  - [Effect of thermal processing of Bacillus intermedius ribonuclease on its
      catalytic activity and biological properties].
AB  - Bacillus intermedius ribonuclease (binase), which is known to exert a growth
      stimulating effect at low concentrations and a genotoxic effect at high
      concentrations, loses these abilities completely after exposure to 100 degrees C
      for 10 min, but retains approximately 96% of its catalytic activity and
      structural integrity. Other types of modification, such as photoinactivation and
      site-specific mutagenesis, gave rise to enzyme forms with unaltered structure but
      reduced (sometimes to trace amounts) catalytic activity. Genotoxicity was always
      proportional to the catalytic activity of the native enzyme, while a notable
      growth-stimulating effect may be exerted by enzymes with low activity. The loss
      of biological activity of thermoinactivated binase was related to the increase in
      the number of negatively charged groups on the enzyme surface, which led to a
      substantial decline in the adhesive properties of the enzyme.

PMID- 11338832
TI  - [Level of cyclic AMP during induction of alternative oxidase in Yarrowia
      lipolytica yeast cells].
AB  - The effect of cyanide, antimycin A, ethanol, and acetate on the induction of
      alternative oxidase in the yeast Yarrowia lipolytica VKM Y-155 sensitive to
      cyanide, in the presence of the aforementioned compounds led to the development
      of cyanide-resistant respiration, which could be suppressed by benzohydroxamic
      acid, an inhibitor of alternative oxidases. The incubation of cells with cyanide,
      ethanol, or acetate raised the intracellular pool of cAMP, which attained maximal
      values after a 2- to 3-min incubation, then rapidly decreased to the initial
      value and did not change over the next three hours of incubation. The possible
      role of cAMP in the induction of alternative oxidase in yeast cells is discussed.

PMID- 11338833
TI  - [Adaptation of the phytopathogenic fungus Fusarium decemcellulare to oxidative
      stress].
AB  - The adaptive response of the phytopathogenic fungus Fusarium decemcellulare to
      the oxidative stress induced by hydrogen peroxide and juglone (5-hydroxy-1,4
      naphthoquinone) was studied. At concentrations higher than 1 mM, H2O2 and juglone
      completely inhibited the growth of the fungus. The 60-min pretreatment of
      logarithmic-phase cells with nonlethal concentrations of H2O2 (0.25 mM) and
      juglone (0.1 mM) led to the development of a resistance to high concentrations of
      these oxidants. The stationary-phase cells were found to be more resistant to the
      oxidants than the logarithmic-phase cells. The adaptation of fungal cells to H2O2
      and juglone was associated with an increase in the activity of cellular catalase
      and superoxide dismutase, the main oxidative stress defense of enzymes.

PMID- 11338834
TI  - [Extracellular protein of propionic acid bacteria inhibits induced mutation in
      strains of Salmonella typhimurium].
AB  - A culture of propionic acid bacteria grown in a glucose-containing minimal
      medium, as well as the culture liquid and logarithmic-phase cells obtained from
      this culture, were found to inhibit the base pair substitution mutations induced
      by 4-nitroquinoline N-oxide, N-methyl-N'-nitro-N-nitrosoguanidine, and sodium
      azide and the frameshift mutations induced by 9-aminoacridine. The antimutagenic
      activity of the culture liquid (CL) was presumably due to the presence of an
      extracellular thermolabile protein with a molecular mass of no more than 12 kDa
      based on the facts that this activity considerably decreased after the treatment
      of the CL with pronase, its heating at 92 degrees C, and its dialysis in a
      cellulose sack, which retains substances with molecular masses greater than 12
      kDa. The residual antimutagenic activity of the dialyzed culture liquid was
      probably related to the interaction of the mutagen with thiols, rather than to
      the presence of organic acids (acetic or propionic). Thiols may also contribute
      to the antimutagenic activity of the P. shermanii cells.

PMID- 11338835
TI  - [The role of polysaccharide-containing components of the Azospirillum brasilense
      capsule in adsorbing bacteria on wheat seedling roots].
AB  - Azospirillum brasilense cells deprived of capsular exopolysaccharides completely
      lost their ability to bind wheat germ agglutinin (WGA) and much of their ability
      to attach to wheat seedling roots. The decapsulation of bacterial cells by
      washing them with a NaCl solution led to an increase in the relative
      hydrophobicity of the cell surface. The pretreatment of wheat seedling roots with
      N-acetyl-D-glucosamine (GlcNAc) or the GlcNAc-containing polysaccharide complexes
      stripped from Azospirillum cells reduced their attachment to the roots. Under the
      experimental conditions, 3-h incubation of wheat seedling roots with exponential
      phase azospirilla, bacterial adsorption is mainly driven by the attachment of the
      cells to the roots, whose operation is due to the capsular polysaccharide
      components and the WGA present on the wheat seedling roots.

PMID- 11338836
TI  - [Competence pheromones in bacteria].
AB  - This article deals with general concepts concerning bacterial pheromones,
      including sex pheromones. The data on the structure and mode of action of
      competence pheromones in streptococci and bacilli are discussed, raising the
      question of the selective value of the process of genetic transformation of
      bacterial life activities and evolution.

PMID- 11338837
TI  - [Specificity of sensitivity to mycocin from Tilletiopsis flava BKM Y-2838].
AB  - The mycocinogenous strain Tilletiopsis flava VKM Y-2823 was found to possess
      fungicidal activity at pH 3.5-4.5, which was retained after curing the strain by
      eliminating the extrachromosomal genetic elements. The mycocin produced by the
      strain had a molecular mass of more than 10 kDa and was readily inactivated by
      heating and treatment with protease K. This mycocin was found to be active
      against species of the anamorphic genus Tilletiopsis. The overwhelming majority
      of other representatives of the order Tilletiales, as well as ascomycetous and
      basidiomycetous yeasts, which either form or did not from ballistospores of the
      orders Sporidiales and Tremellales, were resistant to it.

PMID- 11338838
TI  - [Role of the antioxidant system in response of Escherichia coli bacteria to cold
      stress].
AB  - The response of aerobically grown Escherichia coli cells to the cold shock
      induced by the rapid lowering of growth temperature from 37 to 20 degrees C was
      found to be basically the same as the oxidative stress response. The enhanced
      sensitivity of cells deficient in two superoxide dismutases, Mn-SOD and Fe-SOD,
      and the increased expression of the Mn-SOD gene, sodA, in response to cold stress
      were interpreted as both oxidative and cold stresses are due to a rise in the
      intracellular level of superoxide anion. The long-term cultivation of E. coli at
      20 degrees C was also accompanied by the typical oxidative stress response
      reactions--an enhanced expression of the Mn-SOD and catalase HPI genes and a
      decrease in the intracellular level of reduced glutathione (GSH) and in the
      GSH/GSSG ratio.

PMID- 11338839
TI  - [Bacteria--degraders of polycyclic aromatic hydrocarbons, isolated from soil and
      bottom sediments in salt-mining areas].
AB  - Fifteen bacterial strains capable of utilizing naphthalene, phenanthrene, and
      biphenyl as the sole sources of carbon and energy were isolated from soils and
      bottom sediments contaminated with waste products generated by chemical and salt
      producing plants. Based on cultural, morphological, and chemotaxonomic
      characteristics, ten of these strains were identified as belonging to the genera
      Rhodococcus, Arthrobacter, Bacillus, and Pseudomonas. All ten strains were found
      to be halotolerant bacteria capable of growing in nutrient-rich media at NaCl
      concentrations of 1-1.5 M. With naphthalene as the sole source of carbon and
      energy, the strains could grow in a mineral medium with 1 M NaCl. Apart from
      being able to grow on naphthalene, six of the ten strains were able to grow on
      phenanthrene; three strains, on biphenyl; three strains, on octane; and one
      strain, on phenol. All of the strains were plasmid-bearing. The plasmids of the
      Pseudomonas sp. strains SN11, SN101, and G51 are conjugative, contain genes
      responsible for the degradation of naphthalene and salicylate, and are
      characterized by the same restriction fragment maps. The transconjugants that
      gained the plasmid from strain SN11 acquired the ability to grow at elevated NaCl
      concentrations. Microbial associations isolated from the same samples were able
      to grow at a NaCl concentration of 2.5 M.

PMID- 11338840
TI  - [Divergence in the level of DNA hybridization and formation of sibling species in
      the lactic acid bacteria Streptococcus thermophilus].
AB  - Previously, five distinct groups with 80-90% intragroup DNA homology values were
      revealed among 19 lactic acid-producing bacterial strains. The study of 39 new
      strains of thermophilic streptococci in the present work allowed us to reveal the
      sixth DNA homology group. The nine strains of this group are similar, at 55-70%
      DNA homology levels, to the type strain S. thermophilus ATCC 19258. Group VI
      showed a low level of DNA-DNA reassociation (20-30%) with the DNA homology groups
      I, II, III, and V. The intergroup DNA-DNA reassociation values determined from
      DNA renaturation rates varied from 20 to 50%. These data were interpreted as
      indicative of the existence of at least four sibling species among the
      thermophilic streptococci studied.

PMID- 11338841
TI  - [Halonatronum saccharophilum gen. nov. sp. nov--a new haloalkalophilic bacteria
      from the order Haloanaerobiales from Lake Magadi].
AB  - A new alkaliphilic and moderately halophilic chemoorganotrophic anaerobic
      bacterium (strain Z-7986), which is spore-forming, rod-shaped, and has a gram
      negative cell wall pattern, was isolated from the coastal lagoon mud of the
      highly mineralized Lake Magadi (Kenya). The organism is an obligatorily carbonate
      and sodium chloride-dependent. It is a motile peritrichously flagellated rod
      that has developed within 3-17% NaCl concentration (with an optimum at 7-12%
      NaCl) and within a pH range of 7.7-10.3 (with an optimum at pH values of 8-8.5).
      It is a moderate thermophile with a broad temperature optimum from 36-55 degrees
      C and a growth maximum at 60 degrees C. The bacterium catabolizes glucose,
      fructose, sucrose, maltose, starch, glycogen, N-acetyl-D-glucosamine, and, to a
      slight degree, peptone and yeast extract. Its anabolism requires yeast extract or
      casamino acids. Glucose fermentation yields formate, acetate, ethanol, H2, and
      CO2. The bacterium is sulfidetolerant and capable of the nonspecific reduction of
      S0 to H2S. The G + C content of the DNA is 34.4 mol %. The analysis of the 16S
      rRNA sequence revealed that strain Z-7986 belongs to the order Haloanaerobiales
      and represents a new genus in the family Halobacteroidaceae. We suggest calling
      the organism Halonatronum saccharophilum gen. nov. sp. nov. The type strain of
      this species is Z-7986T (= DSM13868, = Uniqem 211).

PMID- 11338842
TI  - [A system of oligonucleotide primers for amplifying nifH genes from various
      taxonomic groups of prokaryotes].
AB  - Based on the analysis of the nifH gene nucleotide sequences from GenBank, a
      system of primers was developed that makes it possible to obtain 370- and 470-bp
      PCR fragments of the nifH gene of nitrogen-fixing bacteria and archaea. The
      effectiveness of the proposed system for revealing the presence of nifH genes was
      demonstrated by PCR on the DNA isolated from nitrogen-fixing prokaryotes for
      which the primary structure of these genes is known and which belong to different
      taxonomic groups. nifH sequences of nitrogen-fixing prokaryotes of the genera
      Xanthobacter, Beijerinckia, and Methanosarcina, for which the capacity for
      nitrogen fixation was demonstrated earlier, but no data existed on the nucleotide
      composition of these genes, were determined and deposited in GenBank.

PMID- 11338843
TI  - [Phylogenetic analysis of aerobic methylotrophic bacteria, using
      dichloromethane].
AB  - The phylogenetic relationships of 12 aerobic dichloromethane-degrading bacteria
      that implement different C1-assimilation pathways was determined based on 16S
      ribosomal RNA sequences and DNA-DNA hybridization data. The restricted
      facultative methylotroph "Methylophilus leisingerii" DM11 with the ribulose
      monophosphate pathway was found to belong to the genus Methylophilus cluster of
      the beta subdivision of the phylogenetic kingdom Proteobacteria. The facultative
      methylotroph Methylorhabdus multivorans DM13 was assigned to a separate branch of
      the alpha-2 group of Proteobacteria. Paracoccus methylutens DM12, which utilizes
      C1-compounds via the Calvin cycle was found to belong to the alpha-3 group of the
      Proteobacteria (more precisely, to the genus Paracoccus cluster). Thus,
      phylogenetic analysis confirmed the taxonomic status of these recently
      characterized bacteria. According to the degree of DNA homology, several novel
      strains of methylotrophic bacteria were divided into three genotypic groups
      within the alpha-2 group of the Proteobacteria. Genotypic group 1, comprising
      strains DM1, DM3, and DM5 through DM9, and genotypic group 3, comprising strain
      DM10, were phylogenetically close to the methylotrophic bacteria of the genus
      Methylopila, whereas genotypic group 2 (strain DM4) was close to bacteria of the
      genus Methylobacterium. The genotypic groups obviously represent distinct taxa of
      methylotrophic bacteria, whose status should be confirmed by phenotypic analysis.

PMID- 11338844
TI  - [Colony structure of a consortium of nitrogen-fixing bacteria].
AB  - Colonies produced by a consortium of nitrifying bacteria were studied using light
      and electron microscopy. The colonies were obtained by direct plating of inoculum
      from a two-stage nonsterile chemostat fermentor and by repeatedly passing the
      microbial community of the fermentor through selective media containing ammonium
      or nitrite. The colonies studied can be characterized by a specific combination
      of six types of cells differing in their ultrastructure and spatial location
      within the colony. The types of cells occurring within a given colony were found
      to depend on the nitrogen compound present in the medium. As a result of our
      study, morphological features of colonial bacterial communities were
      preliminarily identified. The proposed approach can be viewed as a method to
      describe microbial associations and communities.

PMID- 11338845
TI  - [Features of the association of Helicobacter pylori infection and ulcer in
      Europeans and Mongoloids in Siberia].
AB  - AIM: To study association between Helicobacter Pylori infection in ulcer in
      native population and migrants in Siberia. MATERIALS AND METHODS: Epidemiological
      survey of ulcer has been performed in Northern (Evenkia, Yakutia) and Southern
      (Khakasia) regions of Siberia. Clinical examination covered 3908 Europeoids
      (Russians, Ukrainians) and 1999 Mongoloids (Evenks, Evens, Khakases). Endoscopic
      examination was made in 2144 patients. Light microscopy has detected Helicobacter
      pylori (HP) in 453 patients (215 migrants and 238 natives). RESULTS: Prevalence
      of ulcer in the South of Siberia was 6.1 and 1.5% for migrants and natives,
      respectively. In the North--8.9 and 0.6%, respectively. HP was diagnosed in 83.7%
      of Mongoloids and 69.2% of Europeoids in the South and 92.2 and 100%,
      respectively, in the North. HP index, contamination and adhesion in migrants were
      higher than in native population. CONCLUSION: Siberial Europeoids and Mongoloids
      have specific ethnic features of ulcer occurrence and its association with HP.
      Native population is protected better from the pathogenic bacteria. Further study
      of the causes of virulent bacterial properties and mechanisms maintaining long
      persistance of HP in the stomach is necessary.

PMID- 11338846
TI  - [Immunogenetic aspects of duodenal ulcer in Helicobacter pylori positive
      Europeans in Western Siberia].
AB  - AIM: To study HLA associations with HP-positive duodenal ulcer (DU). MATERIAL AND
      METHODS: A total of 47 Europeoid DU and 680 healthy subjects were examined for
      class I and II HLA antigens. Typing of class I antigens was conducted in the
      microlymphocytotoxicity test, of class 2 antigens--by polymerase chain reaction.
      RESULTS: The study has found associations of duodenal ulcer with HLA-A10, -B41
      and different combinations of these alleles whereas HLA-A9 was protective. A
      relative risk of peptic ulcer was 3.03 in HLA-A10 (pcor < 0.05) and 7.78 in HLA
      B41 (p < 0.001). The allele A9 occurred more frequently in healthy controls
      (30.15%) than in Helicobacter pylori-positive patients with DU (10.64%, RR =
      3.50, pcor < 0.05). Frequencies of alleles HLA-DR7 and HLA-A1/B12 were higher in
      HP-positive DU patients with family history of peptic ulcer (RR = 4.00 and RR =
      11.92, respectively, p < 0.05). CONCLUSION: These data suggest that HLA may
      influence duodenal ulcer susceptibility and resistance. The relationships help
      prognosticate not only development of the disease in HP infection but also the
      age of the infection manifestation.

PMID- 11338847
TI  - [Interleukins in chronic viral hepatitis].
AB  - AIM: To estimate interleukines levels in chronic hepatitis (CH) in respect to CH
      etiological factor, activity and stage. MATERIAL AND METHODS: Enzyme immunoassay
      (kits from proteinovy Kontur, St-Petersburg) determined levels of IL-1 beta, IL
      4, IL-6 and TNF-alpha in the peripheral blood of 250 patients with chronic
      hepatitis C (CHC), B (CHB), D (CHD) and G (CHG). RESULTS: IL concentrations in
      chronic viral hepatitis depend on etiological factor (CHC, CHB, CHD, CHG),
      activity (high, moderate, low), stage (chronic hepatitis, cirrhosis). IL occur in
      high quantities in CHC, in moderate concentrations in CHB and in minimal ones in
      CHG. Maximal IL levels were observed in high hepatitis activity at the stage of
      hepatic cirrhosis. TNF-alpha and IL-4 concentrations rose more frequently and
      higher than IL-6 and IL-1 beta (43 and 34%, up to 315 pg/ml and 256 pg/ml,
      respectively).

PMID- 11338848
TI  - [Clinico-immunological variants of the course of chronic pancreatitis].
AB  - AIM: To study relationships between clinical course of chronic pancreatitis (CP)
      and humoral immunity in CP patients. MATERIAL AND METHODS: Humoral immunity to
      structural and secretory pancreatic components and some phlogogenic factors of
      humoral and cellular origin as well as distribution of HLA antigens were studied
      in 115 CP patients. RESULTS: Two variants of CP course were identified:
      immunologically dependent and immunologically independent. These variants have
      typical clinical, laboratory, immunological and immunogenetic differences.
      CONCLUSION: Identification of immunologically dependent variant of CP has both
      fundamental and practical value as it enables more precise prognosis of the
      disease clinical course and differential approach to its treatment.

PMID- 11338849
TI  - [Prevalence and risk factors of the development of irritable bowel syndrome in
      adolescents: a population study].
AB  - AIM: To determine prevalence of irritable bowel syndrome (IBS) and associated
      factors in a community-based population of adolescents. MATERIAL AND METHODS: 189
      schoolboys and 250 schoolgirls aged 14-17 years from four randomly chosen schools
      of Novosibirsk participated in the study. RESULTS: The prevalence of IBS defined
      according to Rome criteria was higher in girls (24 vs 14% in boys, p = 0.01).
      Colonic pain frequency was similar in both genders (11% in girls vs 9% in boys, p
      = 0.46), however disturbed defecation occurred significantly more often in girls
      than in boys (16 vs 7%, p = 0.003). Half of the subjects who reported IBS had
      also dyspeptic symptoms. Fiber-rich diet and/or laxatives to prevent constipation
      were used by 2% of boys and 7% of girls (p = 0.012). However, only one third of
      those having less than 3 stools a week thought it abnormal. IBS is associated
      with the age over 15-16 years, female gender, abdominal pain in childhood,
      appendectomy, irregular meals and smoking (in girls). No association was found
      with other socio-demographic factors and serological markers of some infections
      and invasions (H. pylori, G. lamblia, O. felineus, hepatitis viruses B and C). Of
      the persons with diagnosable IBS, 49% have consulted a physician about it, 21%
      have undergone upper endoscopy. School absenteeism was reported by 62% of the IBS
      sufferers. CONCLUSION: IBS is common among adolescents (especially girls) with
      the prevalence rates similar to those described in adults from West Europe and
      USA. These disorders are associated with significant disability and health care
      costs.

PMID- 11338850
TI  - [Postinfarction remodeling of the left atrium and left ventricle: effects of long
      term treatment with beta adrenergic blockers and angiotensin converting enzyme
      inhibitors].
AB  - AIM: To study changes in left atrial volume, geometry and function in myocardial
      infarction (MI) patients treated with beta-adrenoblocker and ACE inhibitor.
      MATERIAL AND METHODS: 65 patients with Q-wave myocardial infarction (MI) were
      followed up for 6 months. Regular check-ups included clinical examination, ECG,
      echo-CG, dopplercardiography. RESULTS: In MI patients left ventricular remodeling
      is associated with left atrial remodeling. The greatest inhibition of remodeling
      in patients with symptoms of cardiac failure was reached with captopril therapy.
      Atenolol in this respect is less effective. If cardiac failure in MI patients is
      absent, atenolol impact on the remodeling is stronger than that of captopril.
      CONCLUSION: In postmyocardial infarction patients remodeling occurs in both heart
      chambers. The presence of cardiac failure affects remodeling inhibition rate,
      especially under treatment with beta-adrenoblocker.

PMID- 11338851
TI  - [Circadian rhythm of arterial pressure and state of target-organs in patients
      with mild and moderate hypertension].
AB  - AIM: To assess the state of target-organs in males with mild and moderate forms
      of essential hypertension (EH) in normal and disturbed 24-h rhythm of arterial
      pressure (AP). MATERIAL AND METHODS: Target-organs were examined in 70 males aged
      30-62 years (mean age 49 +/- 1 years) with mild (n = 54) or moderate (n = 16) EH.
      The following tests were performed: ophthalmoscopy, echo-CG with estimation of
      the left-ventricular myocardial mass index (LVMMI), duplex scanning of the
      carotid arteries (DS), AP monitoring, measurements of plasma creatinine, relative
      density of the urine, glomerular filtration rate, examination of the neurological
      status. Circadian rhythm of AP was evaluated by a night fall (NF) of systolic
      pressure (SP). Patients with inadequate NF of SP (< 10%) entered group 1, those
      with normal NF of SP (10% < NF SP < 20%) were allocated to group 2. RESULTS:
      Patients of group 1 had a significantly higher LVMMI, more frequent occurrence of
      left ventricular hypertrophy and carotid artery affection (local thickening
      "intima-media"). In group 1 there was also a complex of unfavourable changes in
      AP circadian profile, especially at night. CONCLUSION: Mild/moderate EH with
      insufficient NF of SP is associated with more pronounced and frequent changes in
      the target-organs (left-ventricular hypertrophy, "intima-media" thickeing).
      Insufficient NF of AP initiates higher pressor load on the target-organs, on the
      one side, and reflects defective regulation which affects target-organs, on the
      other. Both these factors contribute to damage of the target-organs.

PMID- 11338852
TI  - [Evaluation of the evenness of the antihypertensive effect of losartan and
      captopril by using a 24-hour monitoring of arterial pressure].
AB  - AIM: To investigate 24-h evenness of an antihypertensive effect of angiotensin II
      receptor blocker losartan vs captopril by four parameters of arterial pressure
      (AP) monitoring. MATERIAL AND METHODS: An open, cross-over, placebo-controlled
      trial was made in 22 patients with mild/moderate arterial hypertension (AH). Four
      parameters of AP monitoring were assessed: TPR, SI, rate of AP morning rise,
      index of AP morning rise. RESULTS: In losartan treatment TPR for systolic and
      diastolic AP were 61.5 and 61.3%, respectively, IS made up 0.74 +/- 0.13 and 0.64
      +/- 0.09, respectively. For captopril these values reached 21.2 and 26.9%, 0.51
      +/- 0.14 and 0.47 +/- 0.10, respectively. Differences by SI between the two drugs
      were statistically insignificant. Both drugs did not raise the rate and index of
      AP morning rise significantly. CONCLUSION: When administered in a single daily
      dose 100 mg, losartan produced a regular antihypertensive effect throughout 24
      hours. Captopril (twice a day in a dose 50 mg) effect was not regular enough.
      This means that some patients need a three-times-a day regimen of captopril. Of
      the four parameters, SI is most informative for evaluation of antihypertensive
      effect evenness.

PMID- 11338853
TI  - [Reactivity of cerebral vessels in patients with circulatory encephalopathy,
      arterial hypertension and cerebral hypoperfusion risk].
AB  - AIM: To study cerebral vasomotor reactivity (CVR) in patients with chronic
      cerebrovascular disturbances caused by arterial hypertension (AH) and to
      determine criteria of cerebral hypoperfusion risk during antihypertensive
      therapy. MATERIAL AND METHODS: 80 patients with chronic cerebrovascular
      disturbances because of AH and 15 normotensive subjects without any neurological
      pathology (control group) were examined using CT of the brain, duplex scanning of
      extra- and intracranial arteries, echocardiography. CVR was assessed with
      transcranial dollperography of the blood flow velocity in both middle cerebral
      arteries before and after nitroglycerine provoked test. RESULTS: CVR in the
      patients significantly differed from that of the controls. Main factors
      responsible for changes in CVR ara the age, form and duration of arterial
      hypertension, circadian rhythm of blood pressure, occlusive extra- or
      intracranial arteries disease. CT signs of focal (lacunes) or diffuse
      (leukoaraiosis) ischemic brain damage, deformations of the neck vessels, left
      ventricular hypertrophy may be leading markers of severe disturbances in CVR.
      CONCLUSION: In patients with chronic cerebrovascular disease disturbances of CVR
      arise due to arterio/arteriolopathy as a result of AH. Limitation of the
      vasodilatation potential demonstrates cerebral autoregulation dysfunction. Thus,
      factors and markers of CVR impairment can be considered as risk criteria of
      cerebral hypoperfusion during inadequate antihypertensive treatment.

PMID- 11338854
TI  - [Cryoapheresis in the treatment of patients with cryoglobulinemic
      mesangiocapillary glomerulonephritis and acute kidney failure].
AB  - AIM: To assess cryoapheresis (CA) efficacy in the treatment of cryoglobulinemic
      glomerulonephritis (CG) with acute renal failure (ACR). MATERIAL AND METHODS: Ten
      34-64-year-old CG patients with associated HCV infection and symptoms of ACR
      (diuresis under 500 ml/day, serum creatinin 1.6-8.1 ml/dl). All the patients were
      examined clinically, for serum cryoglobulins, HCV, HBV markers, morphologically
      (renal and hepatic biopsies in 8 patients). All the patients received therapy
      with CA, immunodepressants. Three patients with virus replication received, in
      addition, antiviral drugs (alpha-interferon in a dose 3,000,000-5,000,000 IU 3
      times a week intramuscularly for 6 months). RESULTS: CA in combined CG therapy
      led to fast elimination of cryoglobulins from the body, stabilization of renal
      function with arrest of rapid progression of renal failure, normalization of
      diuresis with subsequent lowering of serum creatinin. The course of CA normalized
      renal function fully in 3 patients, partially in 7 patients. Later, these 7
      patients developed chronic renal failure. Complete elimination of the virus and
      remission of CG were achieved in 2 of 3 patients who had undergone the antiviral
      treatment for a year. CONCLUSION: CA can be added to combined therapy of CG
      aggravation as it improves renal function.

PMID- 11338855
TI  - [Advances in the diagnosis and treatment of cholelithiasis].

PMID- 11338856
TI  - [Several hormonal indices during hemofiltration in patients with acute kidney
      failure].
AB  - AIM: To study hormonal aspects of hemofiltration (HF) in acute renal failure
      (ARF). MATERIAL AND METHODS: Hydrocortisone (HC), thyroxine (T4),
      triiodothyronine (T3), TSH, thyrocalcitonine (TC), PTH, insulin (I), C-peptide
      (CP), STH, beta-endorphine (BE) were examined for plasma content, elimination
      with filtrate, sifting rate, filtration clearance in 29 patients with oliguric
      ARF (18 males and 11 females) aged 12-62 years. 19 patients underwent
      intermittent HF (rate 145.2 +/- 9.2/27-260/ml/min, volume 1.02 +/- 0.20/0.45
      1.43/). 10 patients received continuous HF (rate 25.9 +/- 2.3 l/day or 0.36 +/-
      0.05/0.17-0.95/). The hormones were measured with radioimmunoassay. The results
      were processed with variate statistics using Student's criterium. RESULTS:
      Oliguria was associated with high plasma levels of HC, PTH, TC, I, CP; normal
      levels of TSH and STH, low ones of T4, T3 and BE. Intermittent HF led to an
      increased plasma concentrations of HC, T4, I, CP, decreased one of PTH, while TC,
      TSH, STH and T3 remained unchanged. The filtration rate of the hormones was
      different. The elimination was greatest for HC, T4, T3, BE. Concentration of the
      former three in the filtrate surpassed that in blood plasma. CONCLUSION: Besides
      intensive elimination of the hormones with low molecular mass (HC, T4, T3), HF
      causes elimination of appreciable quantities of BE, PTH, I, CT and, probably,
      other peptide hormones. Plasma levels of hormones did not reflect their
      elimination with filtrate.

PMID- 11338857
TI  - [Comparative evaluation of tissue microcirculation in patients with aseptic
      necrosis of the femur head in rheumatoid arthritis and systemic lupus
      erythematosus].
AB  - AIM: Comparative investigation of tissue microcirculation above hip joints
      affected with verified aceptic necrosis of the heads of the femur (ANHF) in
      patients with rheumatoid arthritis (RA) and SLE. MATERIAL AND METHODS: The
      microcirculation was compared in 44 RA and 22 SLE patients. Capillary blood flow
      above the necrotic heads of the femur was studied by 133-Xe clearance from the
      intratissue depot. Laser doppleroflowmetry examined basal blood flow and factors
      of its regulation. RESULTS: Effective skin blood flow decreased both in RA and
      SLE patients at ANHF stage I, remained low at stage II, went up a little at stage
      III. At stage IV the flow continued to rise in RA patients but fell sharply in
      SLE. Laser dopplerflowmetry with functional tests reflects ANHF evolution both in
      RA and SLE. CONCLUSION: Changes in capillary blood flow in SLE above the necrotic
      heads of the femur are more severe and account for more extensive destruction in
      the heads of the femur than in patients with RA.

PMID- 11338858
TI  - [Osmotic activity of plasma in plasmapheresis in patients with multiple myeloma].
AB  - AIM: To control safety and efficiency of therapeutic plasmapheresis (PA) by
      osmolality, colloido-osmotic pressure (COP), total protein concentration before
      and after the procedure in patients with paraproteinemic hemoblastosis. MATERIAL
      AND METHODS: 20 patients with multiple myeloma have undergone 42 PA procedures
      conducted by two techniques: continuous flow centrifugation on blood fractioners
      or intermittent centrifugation of blood in plastic containers. The removed plasma
      volume averaged 1/3 (group 1) or 2/3 of the plasma volume (group 2). The removed
      protein reached 62-197 g. Isotonic sodium chloride solution and/or reopolyglucin
      (20-60 g) replaced the removed plasm. Total protein concentration was measured
      colorimetrically in biuretic reaction, plasma osmolality--cryoscopically and COP-
      on Knauer osmometer. RESULTS: PA leads to a short decline in osmolality (97.0
      99.1%), of total protein concentration (82.8-78.6%) and of COD (79.2% in
      replacement with saline and 90.2% in replacement with dextran). During recovery
      after the procedure plasma osmotic activity and protein concentration return to
      the baseline. CONCLUSION: In elimination of 1/3 of plasma volume and crystalloid
      infusion, hemodilution promotes release of abnormal proteins from the tissues
      into the circulation and thereafter removal them from the organism. In removal of
      1/2 and more of plasma volume, COP demans correction made by administration of
      colloids, e.g. solution of low molecular dextran. There is a potential danger of
      COD lowering several hours after PA due to different speed of dextran elimination
      and mobilization of protein reserve.

PMID- 11338860
TI  - [Primary sclerosing cholangitis associated with autoimmune hepatitis].

PMID- 11338859
TI  - [Relations of acid-base balance and gastric secretion of hydrogen carbonate ions
      in patients with peptic ulcer].
AB  - AIM: To study acid-base balance (ABB) of the organism, gastric secretion of
      hydrocarbonate (HCO3-) in ulcer patients and to examine their relationships.
      MATERIAL AND METHODS: ABB in capillary or venous blood before and after losec and
      famotidine treatment and gastric secretion of HCO3- were studied in 72 patients
      with ulcer. RESULTS: It was found that patients with gastroduodenal ulcer have
      metabolic, less frequently hypercapnic acidosis with suppressed gastric secretion
      of HCO3-. This entails abnormal neutralization of the hydrochloric acid imitating
      high acidity of the gastric juice. HCO3- secretion is inversely proportional to
      pH. H2-blockers normalize ABB in ulcer patients while losec either stimulates
      acidosis or transforms one kind of acidosis into another. CONCLUSION: ABB and
      gastric secretion of HCO3- are related. Acidosis in ulcer patients leads to
      reduction of HCO3- production and intensification of hydrochloric acid secretion.

PMID- 11338861
TI  - [Bartter's syndrome with hyperuricemia].

PMID- 11338862
TI  - [Alcoholism and alcohol disease].

PMID- 11338863
TI  - [Intestinal dysbacteriosis: current aspects of studying the problem, principles
      of diagnosis and treatment].

PMID- 11338864
TI  - [Role of viruses in the development of rheumatoid arthritis].

PMID- 11338865
TI  - [Antitumor activity of dietary fiber: for or against?].

PMID- 11338866
TI  - [Current possibilities of X-ray diagnosis of small intestine diseases using the
      agent Entero-view].
AB  - The paper analyzes the current capacities of routine (classical) X-ray study in
      the diagnosis of organ diseases of the small bowel. The distinctive feature of
      the paper is that in addition to routine barium passage through the small bowel,
      the new barium contrast agent Entero-view specially designed for its exploration
      is used. Of the 115 examined patients with various gastroenterological diseases,
      76 underwent Entero-view examination that revealed different organ pathology of
      the small bowel in 28 cases (Crohn's disease in 18, tuberculosis in 3, lymphomas
      in 5, and cancer in 2). A normal X-ray pattern of the small bowel was diagnosed
      in 48 cases. The authors highly appreciate this agent. In their opinion, it is
      essentially helpful in solving one of the most difficult problems in X-ray
      gastroenterology--present-day X-ray diagnosis of small bowel pathology. The paper
      describes a procedure for using this agent. It gives a normal X-ray pattern of
      the small bowel, the agent's use has provided a particularly vivid image of both
      a normal part of the ileum and its different organ pathology-associated changes.

PMID- 11338867
TI  - [Percutaneous transhepatic intrabiliary intervention in patients with
      cholestasis].
AB  - Percutaneous transhepatic paracentesis of the biliary ducts with ultrafine
      needles may be included into the list of recent great advances of roentgenology.
      It drastically enhances the efficiency of radiation diagnosis of obstructive
      diffuse jaundice. The diagnostic value of this technique was even higher than
      that of computed tomography and, the more, ultrasound diagnosis. The
      potentialities of simultaneous biliary duct catheterization have expanded the
      range of the procedure and made it possible to combine diagnosis with the
      therapeutical manipulation decompression of a suprastenotic part of the dilated
      biliary tree.

PMID- 11338868
TI  - [Use of modified irrigoradioscopy in the diagnosis of external and internal
      rectal prolapse].
AB  - The paper gives colonic X-ray findings in 39 patients with rectal prolapse. Of
      them, 20 and 19 patients were found to have internal and external rectal
      prolapse, respectively. Studies were conducted by the modified irrigoscopy
      developed by the State Coloproctology Research Center, Ministry of Health of the
      Russian Federation, to explore the anatomic and functional status of the rectum
      and the fundus of the pelvis in patients with impaired defecation. The X-ray sign
      of circular invagination that had been detected by the authors allowed them to
      make the diagnosis of internal rectal prolapse with the greatest assurance. The
      modified irrigoscopy in combination with oral enterography for external rectal
      prolapse could show associated changes, including enterocele and sigmocele.

PMID- 11338869
TI  - [Possibilities of CT and US in the diagnosis of colonic cancer].
AB  - The data of examination of 59 patients with colonic cancer were used to consider
      the potentialities of transabdominal, transrectal ultrasonography and X-ray
      computed tomography and to assess their value in diagnosing colonic cancer,
      including its "minor" forms. The paper describes the ultrasound and computed
      tomographic semiotics of colonic cancer and determines a place of the above
      techniques in the algorithm of radiation and instrumental studies. Inclusion of
      these techniques into the diagnostic algorithm may solve a range of
      differentially diagnostic problems and allows a preliminary analysis to be made
      in a tumor lesion according to the International TNM classification.
      Ultrasonography and X-ray computed tomography should be included into a range of
      basic methods for diagnosis of colonic cancer.

PMID- 11338870
TI  - [Possibilities of ultrasonography in the differential diagnosis of strangulation
      and obturation forms of commissural small intestine ileus].
AB  - The main aim of this paper, by the authors' intention, was to attempt to study
      and provide evidence for that routine transabdominal sonography has great
      capacities in diagnosing small intestinal strangulation and obstruction ileus
      caused by commissures or tumors. The data of 48 cases of small intestinal ileus
      (27 of its strangulation form and 21 of its obturation one) were analyzed. The
      paper details guidelines on ultrasonographic techniques and the ultrasound
      semiotics of this pathology. It is the first time that the authors give
      individual methodological and semiotic approaches at sonography in this group of
      papers. They present a particularly clinical picture in combination with
      ultrasonographic data by providing their constant comparison, which serves as an
      additional support of the results of this paper. In the authors' opinion, the
      findings suggest that transabdominal sonography may be a successful basic
      diagnostic technique for strangulation and obturation forms of small intestinal
      ileus.

PMID- 11338871
TI  - [Clinical and X-ray features of pneumonia in drug addicts].
AB  - The authors observed 68 drug addict in-patients, who received treatment for the
      pneumonia at the Primorski Regional Clinical Hospital and Vladivostok Municipal
      Clinical Hospital No. 1. The article details the specific features of the
      pneumonia of these in-patients. It was distinguished the 3 groups of hospital
      patients with the following characteristic features: patients with the
      respiratory distress syndrome of the adults; patients with the primary infective
      endocarditis mainly with the damage of respiratory (right) heart; patients with
      non-specific pneumonia. The peculiarities of the clinical process with the X-Ray
      pictures of the disease were also presented. The article identifies the acute
      beginning of the disease; the strongly pronounced intoxication syndrome; the
      usual cases of the late going to hospital of those patients; the extensiveness of
      the damage; the occurrence of the following complications at the early stage:
      pulmonary destruction, exudative pleurisy, empyema; the long period of the
      disease process; the development of the extensive pulmonary fibrosis. It was
      identified the 33.7% lethality for these groups of in-patients, while the average
      lethality of the in patients treated for pneumonia was 3.3% for the same period
      of time. The complicated pneumonia process of young patients with the infective
      endocarditis with damages of respiratory (right) hearts let us suppose their drug
      addiction.

PMID- 11338872
TI  - [Diagnosis of focal nodal hyperplasia of the liver (data of a complex study:
      magnetic resonance tomography, computed tomography, ultrasonography)].

PMID- 11338873
TI  - [Nephrotoxicity of X-ray contrast media].

PMID- 11338874
TI  - [Value of angiography in the diagnosis of renal cancer].

PMID- 11338875
TI  - [Principles, current possibilities and prospects of radiation diagnosis in
      ophthalmological practice].

PMID- 11338876
TI  - [New technological capacities of the 3d millennium mammography. Proceedings of
      ECR-2000, Vienna, March 4-10, 2000].

PMID- 11338877
TI  - OSHA's revised record-keeping requirements.

PMID- 11338878
TI  - Mitoxantrone and paclitaxel combination chemotherapy in metastatic breast cancer.
AB  - This study evaluated mitoxantrone and paclitaxel combination chemotherapy in the
      treatment of patients with metastatic breast cancer. Thirty-seven patients who
      had developed progressive disease after prior chemotherapy were treated with
      mitoxantrone (14 mg/m2) and paclitaxel (150 mg/m2) every 21 days for a maximum of
      six cycles. The most frequent grade 3 or 4 nonhematological toxicities were fever
      and nausea. Grade 4 neutropenia occurred in 71% of patients. Cardiotoxicity
      occurred in 2 patients, both of whom had previously received doxorubicin.
      Objective response was achieved in 35% of patients (5% complete response and 30%
      partial response) and 41% had stable disease. Median time to disease progression
      and median survival were 6 and 12 months, respectively. The percent of patients
      with an objective response was not different for those who had received prior
      doxorubicin or had chemotherapy in the preceding 6 months. This regimen appears
      to be effective and well tolerated as salvage therapy and merits further
      evaluation.

PMID- 11338879
TI  - A phase II study of weekly alternating chemotherapy in extensive-stage small cell
      lung cancer.
AB  - Despite the recent development of new chemotherapeutic agents with activity in
      small cell lung cancer (SCLC), the long-term prognosis of patients with extensive
      stage disease remains poor and has not improved in the past 20 years. The present
      study was designed to evaluate the activity and toxicity of weekly, alternating
      regimen chemotherapy in patients with extensive-stage SCLC. Patients with
      previously untreated extensive-stage SCLC and performance status 0-2 were treated
      with cyclophosphamide 250 mg/m2, etoposide 100 mg/m2, and cisplatin 50 mg/m2 on
      day 1; vincristine 1 mg/m2 on day 8; and ifosfamide 1.2 gm/m2 on days 8 and 9
      with the entire treatment repeated every 14 days. Eighteen patients received
      chemotherapy for a median of 14 weeks (range, 1-35 weeks). Seventeen patients
      (94%) required dose delays and 16 patients (89%) required at least one dose
      reduction due to toxicity. Twelve patients (67%) exhibited an objective response
      (1 complete response, 11 partial response) with a median duration of response of
      18 weeks (range, 8-32 weeks). Median survival was 33 weeks (range, 1-57 weeks)
      with a 1-year survival rate of 22%. Toxicity was primarily hematologic, including
      grade 3-4 leukopenia (82% of patients) and anemia (53% of patients). Only 2
      patients developed grade 3 peripheral neuropathy and none exhibited grade 3-4
      renal insufficiency. This regimen of weekly alternating combination chemotherapy
      resulted in tolerable toxicity as well as response and survival rates comparable
      to those achieved with standard chemotherapy in patients with extensive-stage
      SCLC. However, weekly chemotherapy regimens for the treatment of SCLC remain
      investigational.

PMID- 11338880
TI  - Comparison of serum interleukin-10 (IL-10) levels between normal volunteers and
      patients with advanced melanoma.
AB  - Melanoma is an immunoresponsive malignancy. Interleukin-10 (IL-10) is a potent
      regulator of immunosuppression. The purpose of this research was to define the
      relationship of serum IL-10 to survival in patients with metastatic melanoma.
      Forty-one melanoma patients and 50 normal volunteers were analyzed. The median IL
      10 level as determined by enzyme-linked immunosorbent assay (ELISA) in melanoma
      patients was 8.75 pg/ml compared to < 3.0 pg/ml in normal volunteers (p =
      0.0001). Survival of melanoma patients with an IL-10 level above 10.0 pg/ml was
      365 days compared to 557 days in patients with IL-10 levels less than 10.0 pg/ml
      (p = 0.0259, Wilcoxon). Elevated IL-10 levels were correlated with poor survival.

PMID- 11338881
TI  - Hepatic transport of gluconeogenic substrates during tumor growth in the rat.
AB  - Hepatic gluconeogenic substrates (alanine, lactate, and glycerol) transport have
      been studied in liver plasma membrane vesicles from rats bearing the ascitic
      tumor Yoshida AH-130 hepatoma. Hepatic alanine uptake was increased in membrane
      vesicles from tumor-bearing animals as compared with those isolated from non
      tumor-bearing controls. Although no changes were observed in relation with KM
      (2.19 and 2.10 mM for control and tumor groups, respectively), the presence of
      the tumor caused a clear increase in Vmax (3.07 and 5.04 nmol alanine/mg protein,
      respectively). The time course of lactate uptake showed no differences between
      the tumor-bearing animals and their corresponding controls. Both time course and
      kinetic experiments showed that liver glycerol uptake was due to passive
      diffusion and therefore cannot contribute to explain the enhanced utilization of
      this hepatic gluconeogenic substrate during tumor growth. The results suggest
      that hepatic alanine uptake may be an important factor accounting for its
      increased utilization for glucose synthesis in tumor-bearing rats.

PMID- 11338882
TI  - Hepatic lymphatic mapping: a pilot study for porta hepatis lymph node
      identification.
AB  - The status of the porta hepatis lymph nodes in patients with hepatic metastases
      from colorectal cancer affects their prognosis and management. Lymphatic mapping
      with isosulfan blue dye is well established in breast cancer and melanoma. An
      animal model consisting of three dogs receiving general anesthesia was utilized.
      Each dog underwent a laparotomy and increasing doses of isosulfan blue dye were
      injected into the right medial segment of the liver. Intraoperatively, the
      presence of blue dye in the porta hepatis region was determined and the lymph
      node identified. Continuous physiological monitoring was performed. Serum
      determination of liver function tests, amylase levels, and white blood cell count
      were performed preoperatively and on postoperative days 1, 2, 4, and 7. The
      animals were sacrificed on day 7. A portal lymph node was identified in each case
      and there was no perioperative morbidity or mortality. There were no significant
      alterations in blood pressure or heart rate in the animals. There was a dose
      responsive decrease in the O2 saturation as measured by transcutaneous
      monitoring, but arterial blood gas analysis showed that pO2 levels remained
      stable. There were no significant changes in the liver function tests, amylase
      levels, or white blood cell counts. There was a small increase in alkaline
      phosphatase, which normalized by postoperative day 7. Hepatic injection of
      isosulfan blue dye appears to be safe and effective in identifying porta hepatis
      lymph nodes in the animal model and sets the basis for further study in human
      subjects.

PMID- 11338883
TI  - Interferon-alpha combined with radiotherapy in the treatment of unresectable
      melanoma.
AB  - A case of recurrent and twice resected sinonasal melanoma is presented. The large
      recurrent tumor was found to regress by a concurrent combination of 6660 cGy
      photon radiation and subcutaneous interferon-alpha injections given for a period
      of 8 weeks. Possible mechanisms of potentiation between interferon and radiation
      are discussed. The unexpected result in this case report raises interesting
      questions about this treatment combination.

PMID- 11338884
TI  - Penile cancer and human papilloma virus (HPV) in a human immunodeficiency virus
      (HIV)-infected patient.
AB  - Only a handful of cases of penile carcinoma among human immunodeficiency virus
      (HIV)-infected males have been reported. This is surprising insofar as other
      anogenital malignancies associated with human papillomavirus (HPV) are over
      represented in HIV-infected men and women. Herein we describe the case of an HIV
      seropositive 64-year-old Caucasian with a CD4+ T-lymphocyte count of 550
      cells/mm3 and an invasive squamous cell cancer of the penis. He underwent radical
      penectomy to treat cancer initially confined to the penile shaft and glans penis,
      but ultimately succumbed to complications associated with metastatic disease. HPV
      type 18 was identified by in situ hybridization and polymerase chain reaction
      (PCR) studies in the primary tumor and in groin and lung metastasis. We also
      briefly review current thoughts regarding the epidemiology and pathogenesis of
      penile cancer, particularly in the setting of HPV and HIV co-infection.

PMID- 11338885
TI  - Breast cancer control and African American women: a review.

PMID- 11338886
TI  - Renal cell carcinoma and interferon at the millennium.

PMID- 11338887
TI  - Current treatment of osteosarcoma.
AB  - A comprehensive multidisciplinary approach has transformed osteosarcoma from a
      disease with a modest long-term survival to one in which at least two-thirds of
      patients will be cured. Surgery remains the vital modality for treating the
      primary tumor, whereas adjuvant chemotherapy plays an essential role in the
      control of subclinical metastatic disease. Complete surgical excision of the
      primary tumor remains an essential element of treatment. For many patients, a
      combination of advances in surgical technique, improved imaging modalities to
      accurately document tumor extent, and the effect of neoadjuvant chemotherapy has
      made limb salvage procedures a safe alternative to amputation. In some patients
      for whom complete surgical excision is impossible, the addition of radiation
      therapy may allow local tumor control. The most effective chemotherapy agents
      currently in use include high-dose methotrexate, doxorubicin, cisplatin, and
      ifosfamide/etoposide. The optimal schedule of therapy is still being
      investigated, as is the role of dose intensification. Unfortunately, some groups
      of patients remain at high risk of eventual relapse. Those whose tumors show
      relatively low degrees of necrosis after administration of chemotherapy have
      poorer survival than patients with more chemotherapy-responsive tumors.
      Similarly, patients who present with overt metastatic disease (particularly bone
      metastases), as well as patients with tumors that recur after treatment, continue
      to have an unsatisfactory outcome. These groups, in particular, may benefit from
      future investigations into novel agents, such as biological response modifiers,
      antiangiogenesis factors, and growth receptor modulation.

PMID- 11338888
TI  - Improving rates of cervical cancer screening and Pap smear follow-up for low
      income women with limited health literacy.
AB  - Adult literacy is an independent and important predictor of health behavior. In
      1993, the National Adult Literacy Survey conducted by the U.S. Department of
      Education demonstrated that one-third of the U.S. population over age 16 (44
      million adults) is functionally illiterate. Several studies link low health
      literacy to self-reported poor health status, poor health behavior, and
      inadequate knowledge about disease. Epidemiologic studies of cancer prevention
      have not detected strong racial and ethnic disparities in disease detection and
      progression, resulting in an emphasis on behavioral and intervention-based
      research. Low literacy presents a wide-reaching barrier to disease prevention
      that, unlike race/ethnicity, is potentially modifiable. Here, we explore the
      relationship between health literacy and health behaviors related to cervical
      cancer prevention in an effort to address concerns about low rates of screening
      and follow-up in vulnerable populations. Our goal is to improve our understanding
      of the health impact of low literacy among urban women and to inspire
      interventions that will promote disease prevention behaviors in this population,
      particularly with regard to cervical cancer.

PMID- 11338889
TI  - Diagnosis and management of neuropathic pain in patients with cancer.

PMID- 11338890
TI  - Work to do. AHA's annual meeting will target tough issues.

PMID- 11338891
TI  - Two views on funding. Drug firm's financial support of AMA ethics campaign poses
      a debate.

PMID- 11338892
TI  - JCAHO jumps in. Looking at hospital where patients may have been exposed to brain
      disease.

PMID- 11338893
TI  - Triad, Quorum inch closer. Companies move to clear last legal hurdles to giant
      merger.

PMID- 11338894
TI  - Exception to the rule. Vanguard Health Systems to buy HMO; proves providers can
      run health plans.

PMID- 11338895
TI  - K.C. Blues dissolves HMO joint venture.

PMID- 11338896
TI  - An HMO alternative. Vivius would let docs set own rates, patients pick own docs.

PMID- 11338897
TI  - Lobbyists consider plan B. New aides take stance against payment increases.

PMID- 11338898
TI  - Teamwork university. Harvard program helps healthcare professionals get the
      skills they need to resolve conflicts.

PMID- 11338899
TI  - Web survey. March survey results: healthcare globalization.

PMID- 11338900
TI  - Sinking Medicaid fraud. Operator of N.Y. facilities pleads guilty; possible
      record settlement cited.

PMID- 11338901
TI  - Still struggling. Not-for-profit hospitals post small increase in margins, new
      study shows.

PMID- 11338902
TI  - In God we trust. Tenet's Catholic hospitals follow religious rules; company touts
      benefits.

PMID- 11338903
TI  - Reproductive services kept in CHW (Catholic Healthcare West) deal in California.

PMID- 11338904
TI  - Tapped for $800 million. Drugmakers' joint venture will pay what could be biggest
      fraud settlement.

PMID- 11338905
TI  - Knowledge integration: insight through the E-portal.
AB  - Data become information when they can be summarized and organized into logical
      patterns; information becomes knowledge when it can be manipulated for actionable
      decision making; knowledge becomes insight when contextually relevant and
      temporarily appropriate. This article describes how information technology can
      now be used to provide clinicians with access to both insight and information
      that is context- and event-sensitive. Collaboration between the American College
      of Physicians, medical knowledge experts, Oregon Health Sciences University
      (OHSU), and shared medical systems for framework and infrastructure combine to
      create the ideal environment of complementary and synergistic competencies. This
      article describes the research that is under way at OHSU to determine how to
      deploy medical knowledge derived from these sources and integrate it into the
      clinical workflow; it also examines a vision of how medical knowledge can be
      integrated in the future.

PMID- 11338906
TI  - E-commerce in healthcare: changing the traditional landscape.
AB  - The healthcare industry, with more than one trillion dollars in revenue, accounts
      for about one-seventh of the U.S. economy. A significant portion of this revenue
      is lost to escalating healthcare system costs. This article examines the
      shortcomings of the traditional healthcare delivery system in terms of
      information flow, communication standards, case collections, and IT spending. It
      makes the case that e-commerce has the ability to transact some healthcare
      business more efficiently and cost-effectively. With the Internet as a delivery
      platform, several models offer improvement over the status quo.

PMID- 11338907
TI  - E-health: restructuring care delivery in the Internet age.
AB  - The authors advocate using the Internet to support clinical care teams dedicated
      to monitoring patients who can most benefit. Care teams will provide such
      services as home monitoring for vital signs and supplying patient information.
      They will work with physicians in managing care. The result should be a stronger
      provider-patient relationship.

PMID- 11338908
TI  - Beyond connectivity: what the success of one health plan's e-solution means for
      the future of the healthcare industry.
AB  - This article highlights the statewide success and rapid acceptance by providers
      in North Carolina of PARTNERS National Health Plan's implementation of a
      multipayer Internet connectivity solution for providers, employers, and members.
      PARTNERS is a premier health plan in North Carolina that covers more than 400,000
      lives. The company introduced on-line communication to their network of ten
      thousand providers and has seen the number of on-line users and interactions grow
      by approximately 25 percent a week to represent more than two thousand providers
      in the first six months of roll-out. Providers can now look up eligibility and
      benefits and review and submit claims and referrals on-line; soon they will be
      able to order and review lab results and perform prescription management.
      PARTNERS found their Internet solution in HealthTrio's Intelligent Connectivity,
      which allowed them to create Internet communications without replacing back-end
      office solutions.

PMID- 11338909
TI  - Road map for the development of an e-healthcare strategy.
AB  - This article presents a case study describing how Saint Francis Care developed
      its strategy for using the Internet and e-commerce. Planning strategies are
      discussed, as are implementation plans and expected benefits.

PMID- 11338910
TI  - E-commerce for healthcare supply procurement.
AB  - The total investment of the more than fifty e-commerce startups that entered
      healthcare supply chain management in the past three years has surpassed $500
      million. However, none of these early entrants has delivered on the initial
      promise of restructuring the entire supply chain, replacing the traditional
      intermediaries, or at least achieving substantial revenue. This article offers a
      new business-to-business (B2B) e-commerce solution classification paradigm and
      uses it to analyze the functional requirements for an effective and, efficient
      healthcare supply chain marketplace. The analysis exposes several fundamental B2B
      market complexities that prevent the early entrants from creating a solid
      customer base and reaching desired liquidity goals. It also identifies several
      technological solutions to the problems mentioned. These new technologies create
      a comprehensive and symmetric order-matching engine that is capable of
      aggregating buy orders, requesting quotes from multiple vendors simultaneously,
      and negotiating along multiple criteria.

PMID- 11338911
TI  - Healthcare e-commerce: connecting with patients.
AB  - Electronically connecting with patients is a challenging frontier at which
      technical hurdles are probably exceeded by political, legal, and other barriers.
      The rise of consumerism, however, compels a response focused more on revenue and
      strategic advantage than on pure cost savings. Among the difficulties faced by
      providers is choosing among various models of connectivity and component
      function. Emerging models include "free-floating" personal medical records
      largely independent of the office-based physician, systems with compatible and
      intertwined physician and consumer relationships using an application services
      provider office practice system, and systems that connect patients and providers
      through e-mail, office triage, prescription refills, scheduling, and so on. This
      article discusses these and other combinations of technology that significantly
      overcome the barriers involved and that may be woven together to provide
      solutions uniquely suited to various competitive situations.

PMID- 11338912
TI  - Postmarketing surveillance of medications and pregnancy outcomes: clarithromycin
      and birth malformations.
AB  - PURPOSE: This retrospective surveillance study used linked administrative claims
      data and medical records to determine the rate and types of birth malformations
      in infants born to women exposed to the antibiotic, clarithromycin (Biaxin),
      during the first trimester of pregnancy. METHODS: Pharmacy and hospital claims
      from eight geographically diverse health plans were used to identify women who
      had a delivery claim within 270 days of a clarithromycin prescription over a 5
      year period (1991-1995). Hospital delivery admission medical records for 143
      mothers and their 149 infants were abstracted to identify birth malformations.
      RESULTS: Five infants were identified with major malformations, three with minor
      malformations, and four with undescended testicles likely to resolve with time.
      The observed rate of 3.4% (95% CI, 0.5, 6.3) for major malformations was not
      statistically significantly different compared to an expected rate of 2.8% based
      on earlier national data. There was no consistency across types of major
      malformations. CONCLUSIONS: These results provide no evidence that clarithromycin
      is a likely major teratogen in humans. Use of claims data is one way to evaluate
      quickly and efficiently the safety of prescription medications in humans during
      pregnancy, especially when both exposure and outcome are rare.

PMID- 11338913
TI  - A pharmacodynamic assessment of the impact of antihypertensive non-adherence on
      blood pressure control.
AB  - OBJECTIVES: To evaluate if antihypertensive regimens that conform to present FDA
      guidelines by maintaining > or = 50% of their peak effect at the end of the
      dosing interval protect patients during sporadic lapses in adherence. METHODS:
      169 patients on monotherapy for high blood pressure underwent electronic
      adherence monitoring for 3 months. Blood pressures were measured during non-study
      office visits and were retrieved from automated medical records. Questionnaires
      were used to obtain other covariate information. The ratio of the dosing interval
      to the half-life of drug activity (I') was used to capture conformity with FDA
      guidelines. Data analysis focused on the interaction between I' and the impact on
      blood pressure of delayed dosing. RESULTS: The average (+/- standard deviation)
      blood pressure during the study was 139.0(+/- 12.0)/85.0(+/- 6.9) mm Hg.
      Lisinopril followed by sustained-release verapamil, atenolol, and
      hydrochlorothiazide were the most frequently prescribed agents. The majority of
      regimens (99%) conformed to FDA dosing guidelines. Of the patients 23% missed a
      dose before their blood pressure check. Non-adherence, however, did not have a
      direct impact on blood pressure, and no interaction with I' of was detected.
      CONCLUSIONS: Among patients with relatively mild hypertension on single-drug
      therapy, regimens that conform to current FDA dosing guidelines may prevent
      losses of blood pressure control during episodic lapses of adherence. These
      findings should be replicated in other patient populations with standardized
      blood pressure measurement to confirm their validity.

PMID- 11338914
TI  - Defining the margins for errors in patient compliance with prescribed drug
      regimens.

PMID- 11338915
TI  - Co-morbidity of 'clinical trial' versus 'real-world' patients using
      cardiovascular drugs.
AB  - PURPOSE: To examine discrepancies between co-morbidity of patients included in
      pre-marketing clinical trials of cardiovascular drugs and patients from daily
      practice, representing the actual users after marketing, and to investigate the
      availability of data regarding co-morbidity in registration files. METHODS: Data
      were collected from phase III trials of registration files of 16 drugs,
      registered in the Netherlands in the period 1985 through 1994 for the indications
      hypertension, angina pectoris or hypercholesterolemia, and from a general
      practitioners database. Patients were selected who used drugs from the same
      therapeutic classes for the same indication as the patients in the pre-marketing
      trials. Prevalences of concomitant cardiovascular, endocrine and metabolic
      diseases were compared between pre- and postmarketing populations. Discrepancies
      were defined as more than 10% difference in prevalences. RESULTS: Data regarding
      co-morbidity were present in 13 out of 16 registration files and differed in
      format of reporting. For all indications, coexisting cardiovascular, endocrine
      and metabolic diseases were less prevalent in the pre-marketing populations,
      except ischemic heart disease, which was more prevalent coexisting with angina
      pectoris and hypercholesterolemia. Discrepancies were found for hypertensive
      disease, heart failure, diabetes mellitus and myocardial infarction. CONCLUSIONS:
      Phase III trials testing cardiovascular drugs included patients with concomitant
      cardiovascular, endocrine and metabolic diseases, but discrepancies were present
      with patients in daily practice. Development of guidelines for uniform collection
      and reporting of co-morbidity data in pre-marketing trials is recommended, as
      well as further utilization of data.

PMID- 11338916
TI  - Statement 'the use of patient-related information in medical research and the
      health system'.
AB  - Patient-related information is regularly recorded in surgeries and hospitals. The
      health system produces such 'person-related health data' in astronomical numbers.
      Millions of data are entered into and processed by the computing systems of many
      different institutions. They are used for the treatment of patients and the
      calculation of health fund benefits and in addition, given a systematic and
      methodologically controlled evaluation, they can be used to detect health risks,
      assess more accurately the consequences of risks and diseases, compare the
      benefits of different therapies, or rank health care goals. Since health data are
      person-related their recording and use are subject to the consent of the person
      in question. Besides, the information which the patient provides or which is
      established regarding the patient, is protected by the confidentiality to which
      all doctors are held; if it is passed on to calculate health benefits it is
      protected by the confidentiality of social security data. Beyond this moral and
      legal protection the use of person-related health data requires explicit legal
      justification. In view of the multitude of uses which the current level of data
      processing affords, no legal regulation can determine every possible instance
      comprehensively and definitively in advance. Rather, a moral and legal evaluation
      of each instance is needed. It is not without reason that the data protection
      laws contain more or less comprehensive general clauses and indeterminate legal
      concepts. The Central Ethics Commission at the German Medical Association
      (Bundesarztekammer) has put out a statement on these matters. It asks the
      legislature to improve the protection for individuals with respect to the use of
      patient data for research in medicine and the health system in accordance with EU
      Directive (No. 95/46/EG of 24 October 1995). Moral and legal problems occur
      mainly when, for objective reasons, the consent of the persons in question cannot
      be obtained, yet the further use of the data is important in order to improve the
      care of the patients. The Central Ethics Commission suggests the establishment of
      independent bodies along the lines of ethics commissions to undertake the
      necessary judgments between individual protection and the importance of the
      purpose for which the data are to be used. It further argues that if used in
      medical research or the health system the data are given the same degree of
      protection as they were by the doctor to whom they were first confided.

PMID- 11338917
TI  - Is confused thinking the cause of a non-existent dilemma? Current worries about
      patient confidentiality and epidemiological research.

PMID- 11338918
TI  - Effects of a monetary incentive on primary care prescribing in Ireland: changes
      in prescribing patterns in one health board 1990-1995.
AB  - BACKGROUND: In an attempt to curb the rapidly rising costs of primary care
      prescribing in Ireland, the government introduced a financial incentive scheme in
      1993, to encourage general practitioners to restrain their prescribing. PURPOSE:
      To investigate the effects of a financial incentive scheme on GP prescribing in
      Ireland on prescribing costs and volume, and on some specific therapeutic areas.
      METHODS: Prescribing for 3 years before (1990-1992) and 3 years (1993-1995) after
      the introduction of incentives, based on a defined cohort of 233 general
      practitioners in the area of one health board. GPs were divided into tertiles
      based on their performance against their prescribing budgets into 'savers'
      (generally underspent and received incentive payments), modest overspenders and
      large overspenders. RESULTS: Savers were always lower cost prescribers than the
      other groups. They contained their rate and costs of prescribing in contrast to
      the other groups, e.g. percentage rise in prescribing costs in the year after the
      introduction of the scheme -7.9%, +1.2% and +7.3% respectively, (P < 0.05) for
      savers, modest overspenders and large overspenders respectively. This effect was
      short lived however and was gone by the third year of the study. CONCLUSIONS: The
      financial incentives had a marked effect on prescribing volume and cost on some
      practices who could achieve targets and hence incentive payments. The incentives
      had little effect on high spending practices. Such incentive schemes need careful
      evaluation if they are not to become perverse to the good health of patients.

PMID- 11338919
TI  - Misuse of corticosteroids in some of the drugs dispensed as preparations from
      alternative systems of medicine in India.
AB  - Screening for corticosteroids carried out on 120 samples of alternative medicines
      which were dispensed to patients suffering mainly from asthma, arthritis, etc.,
      showed that 38.32% of them were adulterated with steroids. Most of these samples
      were submitted for screening by either a medical practitioner or the patients
      themselves, who suspected effects of steroids from these drugs. The percentage of
      steroid positivity was determined in ayurvedic drugs, homeopathic drugs, and
      unknown or other category of drugs. The presence of steroids in these drugs given
      for different ailments such as asthma, arthritis, and unknown/other ailments was
      also tabulated. The results show that a high percentage of these samples
      contained corticosteroids, however, the distribution of positivity amongst groups
      was not statistically significant. The lack of proper quality control mechanisms
      to verify ingredients or efficacy of 'alternative medicines' has led to the
      proliferation of the practice of dispensing spurious drugs containing
      corticosteroids as alternative medicines. This study aims to highlight the
      existence of 'quick fix' remedies dispensed as 'alternative medicines' which not
      only cause extensive adverse health effects to the patients but also bring
      alternative systems of medicines into disrepute. The deliberate contamination of
      corticosteroids with alternative systems of medicine by some practitioners is a
      cause of great concern. Such practices may not only disgrace alternative systems
      of medicine but may also lead to adverse side-effects on chronic exposure.

PMID- 11338920
TI  - Short-term safety and tolerability of antihypertensive agents in Korean patients:
      an observational study.
AB  - PURPOSE: In order to assess the short-term safety and tolerability of newly
      prescribed antihypertensive monotherapies in Korean patients, a prospective study
      was carried out. METHODS: A total of 1181 patients were observed from July 1997
      to August 1999. At 2, 4, 8 and 12 weeks after initiation of antihypertensive
      monotherapy, the patients were evaluated for whether treatment was to be
      continued and the development of any adverse reactions. RESULTS: During the first
      12 weeks, the percentage of subjects continuing with their initial angiotensin
      converting enzyme inhibitors (ACEI) (40.7%) was substantially lower than that of
      subjects continuing with angiotensin II receptor antagonists (ARA) (66.2%), alpha
      blockers (63.0%), calcium channel blockers (CCB) (61.3%), beta-blockers (55.8%),
      and diuretics (53.5%), respectively (P < 0.01). The following adverse reactions
      were detected: cough (7.5%), headache (6.1%), dizziness (3.9%), flushing (3.7%)
      and impotence (2.4%). Cough, headache, and flushing were more frequent in women,
      and impotence and loss of libido were more frequent in men (P < 0.05). The
      incidence of cough associated with ACEI (27.9%) was higher than that associated
      with the other classes of drugs (P < 0.01). CONCLUSIONS: The tolerability of
      antihypertensive medication was highest in Korean patients treated with ARAs,
      followed by CCBs, beta-blockers, diuretics, alpha-blockers, and ACEIs. The
      incidences of adverse reactions were different by sex, age and drug class.

PMID- 11338922
TI  - Pharmacoepidemiology and drug safety.

PMID- 11338921
TI  - Pharmacoepidemiology in developing countries--what can ISPE do?

PMID- 11338923
TI  - Recent developments in RNA-based strategies for cancer gene therapy.
AB  - The introduction of RNA into mammalian cells is a relatively straightforward
      procedure with many therapeutic applications. An advantage of using mRNA is that
      protein expression can be achieved in post-mitotic or quiescent cells where there
      is usually little or no gene expression with non-viral DNA delivery systems.
      Furthermore, the cleavage of mRNA by catalytic RNA molecules, or ribozymes, is a
      useful strategy to downregulate aberrant gene expression. The purpose of this
      review is to provide an update of current applications that use RNA molecules
      such as mRNA and ribozymes as a basis for gene therapy strategies targeting the
      initiation and progression of cancer. In particular, we focus on recent
      developments that improve the delivery and stability of RNA molecules to achieve
      therapeutic efficacy.

PMID- 11338924
TI  - Satellite DNA-based artificial chromosomes for use in gene therapy.
AB  - Satellite DNA-based artificial chromosomes (SATACs) can be made by induced de
      novo chromosome formation in cells of different mammalian species. These
      artificially generated accessory chromosomes are composed of predictable DNA
      sequences and they contain defined genetic information. Prototype human SATACs
      have been successfully constructed in different cell types from 'neutral'
      endogenous DNA sequences from the short arm of the human chromosome 15. SATACs
      have already passed a number of hurdles crucial to their further development as
      gene therapy vectors, including: large-scale purification; transfer of purified
      artificial chromosomes into different cells and embryos; generation of transgenic
      animals and germline transmission with purified SATACs; and the tissue-specific
      expression of a therapeutic gene from an artificial chromosome in the milk of
      transgenic animals.

PMID- 11338925
TI  - Exploiting chromosomal and viral strategies: the design of safe and efficient non
      viral gene transfer systems.
AB  - The development of gene transfer systems for therapeutic applications depends, to
      a large part, on an understanding of chromosomal elements mediating controlled
      gene expression, and DNA synthesis and maintenance. The integration of transgenes
      into chromosomes assures their faithful replication and segregation due to the
      natural functions of the host chromosome, but their expression is susceptible to
      inactivation by the host-cell apparatus, and they may also cause unwanted
      mutagenic effects. While episomal vectors are free from these shortcomings,
      progress in this field suffers from the lack of an in-depth understanding of the
      accessory functions, although a number of first-generation prototypes have been
      constructed in the past years. As an immediate solution, small non-viral circular
      episomal vectors are emerging which not only permit the study of the relevant
      components in a minimal gene-transfer system, but for which a considerable
      potential for therapeutic applications can be anticipated.

PMID- 11338926
TI  - Evolution of cross-linked non-viral gene delivery systems.
AB  - Developing a non-viral gene delivery system that functions in vivo raises the
      challenge of finding solutions to efficiently deliver DNA to the cell surface
      that are also compatible with the efficient release of DNA into the cytosol. The
      stability, particle size and charge of DNA polyplexes and lipoplexes may be
      optimized to mediate efficient in vitro transfection only to find that different
      properties are necessary for successful in vivo transfection. Despite their
      versatility and improved safety, non-viral gene vectors still lack appreciable in
      vivo transfection efficiency compared to viral vectors. An emerging theme in
      recent studies is the use of cross-linking to achieve balance between the
      stability of polyplexes and lipoplexes in the blood and the controlled release of
      DNA in the cytosol. This review evaluates the evolution of cross-linking
      strategies aimed at transiently stabilizing non-viral gene delivery systems.

PMID- 11338927
TI  - Protein/peptide transduction domains: potential to deliver large DNA molecules
      into cells.
AB  - In vivo gene delivery can be achieved by direct injection of plasmid DNA.
      However, inefficient cellular uptake and nuclear import of plasmid DNA result in
      much lower levels of gene expression than observed when viral vectors are used as
      gene delivery agents. Recent studies have shown that transducing peptides, such
      as the HIV Tat protein, can carry large biomolecules from the extracellular
      environment directly into the cytoplasm and the nucleus of cells, both in vitro
      and in vivo. Thus, TAT-mediated transduction has the potential to increase the
      delivery of plasmid DNA to the nuclei of cells in vivo and thereby increase gene
      expression.

PMID- 11338928
TI  - Long-circulating vectors for the systemic delivery of genes.
AB  - The development of vectors capable of treating systemic diseases is an important
      goal for gene therapy protocols. In order for a carrier system to preferentially
      accumulate at sites of systemic disease, such as tumors, sites of inflammation
      and sites of infection, the carrier must exhibit long circulation lifetimes
      following intravenous injection. Unfortunately, most gene delivery systems,
      including viral vectors as well as non-viral vectors, e.g., lipoplexes,
      polyplexes and lipopolyplexes, are rapidly cleared from the circulation and are
      preferentially taken up by the 'first-pass' organs such as liver, lung and
      spleen. Here we review recent literature concerning the ability of non-viral
      vectors to act as systemic gene therapy agents. The most promising systemic
      vectors are liposomal systems in which plasmid DNA is encapsulated within a lipid
      bilayer. The stabilized plasmid-lipid particle (SPLP) system, for example,
      exhibits circulation half-lives of the order of 6 h following intravenous
      injection, and preferentially accumulates in distal tumors with gene expression
      primarily localized to the tumor site.

PMID- 11338929
TI  - Phage as gene delivery vectors.
AB  - Bacteriophage can be considered as a natural system to efficiently condense and
      package DNA. They tolerate many different types of mutations, including those
      that lead to the display of polypeptides as a fusion to any of the structural
      proteins comprising the phage particle. In addition, they are a powerful
      biological system for generating and screening mutants with the desired
      functional properties. It has also been shown that phage vectors can be
      engineered for receptor-mediated gene transfer to mammalian cells. The attractive
      features offered by this system have paved the way for various attempts to
      develop phage as a vector for gene therapy applications.

PMID- 11338930
TI  - Harnessing nuclear localization pathways for transgene delivery.
AB  - Inefficient transport of DNA from the cytoplasm into the nucleus remains a
      limiting step in the development of non-viral gene delivery systems. This is
      particularly acute in non-dividing cells, where entry to the nucleus is thought
      to occur only through the nuclear pore complex. Active import of physiological
      proteins is mediated by nuclear localization sequences (NLSs) within cargo
      proteins such as transcription factors. Here we review current knowledge of this
      import machinery and consider its exploitation by mammalian viruses. Significant
      research effort has been directed at incorporating NLSs into synthetic gene
      delivery systems to take advantage of this physiological pathway. Both non
      covalent and covalent methods of conjugation are evaluated, with NLS linkage to
      both DNA and carrier, and compared with activities of simple cationic polymers.
      Finally, progress in the field of DNA sequence-specific nuclear import is
      examined and the current state of the technology assessed.

PMID- 11338931
TI  - Polyethylenimines for in vivo gene delivery.
AB  - Branched and linear polyethylenimines (PEIs) are proving to be efficient, non
      toxic and versatile agents for in vivo gene delivery by a number of routes. A
      major factor in the successful use of PEIs seems to be the small size of PEI/DNA
      complexes which can be achieved under controlled conditions of formulation,
      mainly by using PEIs of low molecular weights. This review considers the in vivo
      use of PEI, from formulation to delivery and analysis of gene expression. PEI
      delivery is already used for the analysis of numerous physiological processes. It
      is hoped that scrutiny of the mechanisms involved with PEI-based gene delivery at
      different levels of the transfection process and in different in vivo contexts
      will aid the transition towards its use in therapeutic situations.

PMID- 11338932
TI  - Cationic polymers for gene delivery: designs for overcoming barriers to systemic
      administration.
AB  - Cationic, polymer-based delivery systems have faced limitations in the systemic
      delivery of therapeutic gene drugs due to difficulties in formulation, in vivo
      stabilization, toxicity and low transfection efficiencies. Strategies for
      overcoming some of these barriers have utilized knowledge gained from the fields
      of colloidal stabilization and protein trafficking. This review highlights recent
      efforts in polycation preparations that include the development of new polymers
      for gene delivery, the modification of traditional polycations with hydrophilic
      polymers for salt and serum stability and the addition of bioactive
      functionalities to polymers for enhanced intracellular trafficking. These studies
      have resulted in polymer/DNA composites with increased stability and delivery
      efficiencies.

PMID- 11338933
TI  - Hydrodynamics-based gene delivery.
AB  - The need for a safe and efficient method for gene delivery has stimulated the
      recent emergence of vectorless methods (e.g., naked DNA) as promising
      alternatives to the available viral- and non-viral-based systems. Among these
      methods, hydrodynamics-based gene delivery through systemic injection of DNA
      offers a convenient, efficient and powerful means for high-level gene expression
      in mice. This review deals with the background and progress made so far with this
      new gene delivery method, the potential mechanism underlying the hydrodynamics
      based DNA transfer into cells and its potential applications towards gene
      function analysis, protein expression and gene therapy in whole animals.

PMID- 11338934
TI  - Technology evaluation: C242-DM1, ImmunoGen Inc.
AB  - C242-DM1 is a tumor-activated immunotoxin under development by GlaxoSmithKline
      plc (formerly SmithKline Beecham plc), under licence from ImmunoGen Inc, as a
      potential treatment for colon tumor. It consists of a colon cancer-specific
      humanized antibody, C242, conjugated to the maytansine derivative DM1. In
      preclinical studies, C242-DM1 caused complete tumor regression in animal models
      of both human pancreatic and non-small cell lung cancer (NSCLC) at non-toxic
      doses. C242-DM1 has also been evaluated in an immunoconjugate combination with J
      591 (Cornell University). The J591-DM1 immunoconjugate demonstrated effective,
      antigen-specific delivery of a highly cytotoxic drug to PSMA-positive Pca cells
      in vitro and in vivo with low systemic toxicity. Results from studies in monkeys
      showed that C242-DM1 had no significant toxicity or side effects, when
      administered at doses higher than those that were previously shown to completely
      eradicate human colon tumors in mice [271420]. ImmunoGen acquired the right to
      evaluate, and an option to license, technology related to maytansines from
      Takeda. In February 1999, ImmunoGen and SmithKline Beecham signed a US $45
      million development and commercialization agreement for C242-DM1 [313493]. In
      August 1997, Immunogen received an SBIR grant to advance development of huC242
      DM1 [258356]. EP-00425235, held by ImmunoGen, covers conjugated forms of
      ansamitocin (maytansine) derivatives. Takeda holds several patents for the
      production of ansamitocin and its analogs, the first one being JP-53124692.

PMID- 11338935
TI  - Technology evaluation: CV-787, Calydon Inc.
AB  - CV-787 is a recombinant adenovirus that replicates only in prostate-specific
      antigen (PSA)-producing cells, which is being developed by Calydon Inc for the
      treatment of prostate cancer [339621]. This attenuated replication-competent
      virus (ARCA) only replicates in and destroys PSA-producing cells. By engineering
      the prostate-specific enhancer (PSE) control element into the adenovirus, Calydon
      has established both a means for delivery and the mechanism for killing prostate
      cancer cells [339621]. In October 1999, Calydon began treating patients with
      biopsy-proven, prostate-confined cancer with CV-787 in a phase I/II multi-center,
      open-label, dose-finding study [362188], [344731]. In September 2000, Calydon
      initiated a a phase I/II multi-center, open-label, dose-finding trial of an
      intravenous formulation of CV-787 in men with metastatic prostate cancer
      [384039]. The trial was designed to enrol 48, and enrollment was continuing in
      April 2001. The study is being conducted at three medical centers: University of
      California at San Francisco; Johns Hopkins Oncology Center in Baltimore; and,
      University of Wisconsin at Madison. The primary objectives of this trial are to
      determine the safety, tolerability, and PSA efficacy of CV-787 administered
      intravenously to patients with end-stage prostate cancer [384039].

PMID- 11338936
TI  - Characteristics of proper names and temporal memory of social news events.
AB  - Long-term memory of social news events was investigated by means of a
      questionnaire methodology with a large sample of participants. In Experiment 1, a
      total of 501 university students were asked to give proper names (i.e., persons
      and places) that related to a certain news event, and to estimate the date of the
      event. The accuracy of proper names (especially person names) was superior to
      that of estimated date (i.e., year). In addition, telescoping effects were found
      in the events that occurred more than 3 years ago, but time expansion effects
      emerged in the events that occurred less than 2 years ago. In Experiment 2, in
      which 182 students participated, the accuracy of proper names and the date
      estimates tended to be high on the events that participants judged to be given
      frequent exposure by the mass media. Based on these results, we discuss long-term
      memory and temporal schemata regarding social news events.

PMID- 11338937
TI  - Episodic recall of specifics and generalisation coexist in 25-month-old children.
AB  - It is clear that children generalise their knowledge of events from one
      instantiation to another. The means by which generalisation is accomplished are
      unclear. In three experiments, we used elicited imitation of multi-step sequences
      to test whether 25-month-olds' generalisation occurs as a function of forgetting
      of the features of the original event. Experiment 1 was an initial test of
      generalisation from one version of an event to another version involving
      perceptually different yet functionally analogous props. After a 1-week delay,
      children showed evidence of generalisation by enacting the event using the
      analogous props. Experiment 2 was a within-subject test of generalisation and
      memory for the original version of an event. After a 1-week delay, when paired
      with unrelated distractor props, analogous props served as effective retrieval
      cues; when paired with the original props, analogous props were treated as
      functionally equivalent to unrelated distractors. This within-subject reversal in
      the functional role of analogous props is compelling evidence that children's
      event representations include specific features and, at the same time, are
      generalisable. In Experiment 3, children showed evidence of generalisation
      immediately after exposure to an event, thereby making clear that generalisation
      occurs even in the face of robust memory for the specific features of the
      original event.

PMID- 11338938
TI  - Reducing the saliency of intentional stimuli results in greater contextual
      dependent performance.
AB  - Wright and Shea (1991) described intentional stimuli as explicitly identified
      information necessary to successfully perform a task, whereas incidental stimuli
      are not explicitly identified as crucial to task performance but have the
      potential to become associated with particular responses because of their
      selective presence in the training environment. Shea and Wright (1995), using a
      speeded-choice RT task, indicated that manipulating the strength of association
      between incidental information and the responses, by changing the
      discriminability of incidental stimuli while fixing the strength of the
      association between the intentional stimuli and each response, had a significant
      impact on task performance. The present experiment further examined the role
      played by incidental stimuli when the strength of association between the
      intentional stimuli and the associated responses was reduced, by minimising
      stimulus-response compatibility. It was assumed that this latter manipulation
      would have a similar impact as increasing the strength of incidental stimuli
      response relationships. That is, the relative contribution of the incidental
      stimuli would increase, resulting in an increase in context-dependent behaviour
      during tests in which the intentional and incidental stimuli activated different
      responses. The results were in agreement with this prediction and consistent with
      a model for contextual-dependent performance proposed by Shea and Wright (1995)
      as well as with the outshining hypothesis forwarded by Smith (1988, 1994).

PMID- 11338939
TI  - Flashbulb memories in social groups: a comparative test-retest study of the
      memory of French President Mitterrand's death in a French and a Belgian group.
AB  - Flashbulb memories are vivid and long-lasting memories for the reception context
      of an important public event (Brown & Kulik, 1977). They are assumed to be
      triggered by emotional factors (i.e., intensity of emotional feeling, appraisal
      of the original event) and by social factors (i.e., social sharing of the news,
      following media debate about the event). The present study investigated the
      memory for the death of the former President of France F. Mitterrand in two
      social groups, i.e., French and Belgian people. This study tests whether the
      flashbulb memory attributes, the memory for the original event, and the impact of
      the emotional and social determinants of flashbulb memory differed across groups.
      The results indicated that the flashbulb memory for Mitterrand's death is
      affected by group provenance, as French people showed higher levels of recall for
      the flashbulb memory attributes and their determinants than Belgian people. Time
      impaired recollections in both groups, so that flashbulb memories appear prone to
      decay and share the same destiny as ordinary memories. The theoretical construct
      of concern--as the most basic antecedent of emotional experiences and its related
      appraisal (Frijda, 1994)--is discussed in order to explain the differences in
      memory of the two social groups.

PMID- 11338940
TI  - Intermediate care. Independence way.

PMID- 11338941
TI  - Hospital discharge. Home, but not alone.

PMID- 11338942
TI  - Intermediate care. A suitable case for treatment?
AB  - A study of emergency referrals to GPs and hospital accident and emergency
      departments from nursing homes found that most were appropriate. The most usual
      reasons for referral were chest infections and changes in medication. Referrals
      were fewer than five a month per nursing home. Protocols for emergency referrals
      could improve consistency of care.

PMID- 11338943
TI  - Some things wicked.

PMID- 11338944
TI  - Staff recruitment. A turn for the better.

PMID- 11338945
TI  - Data briefing. Winter pressures.

PMID- 11338946
TI  - Coming clean.

PMID- 11338947
TI  - The place of the electrocardiogram in modern cardiology.

PMID- 11338948
TI  - New national standards for specialist practice in public health.

PMID- 11338949
TI  - Childhood leukaemia: the medical cost of cure.
AB  - More than 1 in every 1,500 individuals in the UK between 16 and 44 years of age
      has survived childhood cancer. This article describes the medical cost of cure in
      survivors of acute leukaemia, the most common form of childhood cancer.

PMID- 11338950
TI  - Management of a lump in the neck.
AB  - This article reviews the management of adults who present with a neck lump, and
      discusses the potential causes and relevant investigations. The review emphasizes
      the avoidance of open biopsy and need for early referral to the appropriate
      specialist.

PMID- 11338951
TI  - Calcification on the chest X-ray: a pictorial review.
AB  - There are numerous causes of calcification on the chest radiograph. Their
      striking appearance can lead to anxiety among junior medical staff. This article
      aims to categorize these appearances, and to give examples of the most common
      causes seen.

PMID- 11338952
TI  - Intrauterine growth restriction: diagnosis and management.
AB  - The diagnosis of intrauterine growth restruction often results in preterm
      delivery with its associated morbidity and mortality. This review aims to outline
      the main diagnostic and management tools available to obstetricians for the
      management of such pregnancies as well as the aetiological factors that might be
      associated with this condition.

PMID- 11338953
TI  - Cryopreservation of human ovarian tissue.
AB  - As survival rates for young cancer patients continue to improve, protection
      against iatrogenic infertility caused by chemotherapy and/or radiotherapy assumes
      a higher priority. As things stand, women patients have few options to preserve
      their fertility while children have none at all.

PMID- 11338954
TI  - The use of botulinum toxin in otorhinolaryngology.
AB  - In recent years, the use of botulinum toxin has become more popular for the
      treatment of a wide variety of diseases in the head and neck. It offers the
      possibility of non-invasive treatment of conditions whose aetiology lies in
      neuromuscular dyskinesis.

PMID- 11338955
TI  - Electrocardiogram interpretation.  Case 1: permanent pacemaker malfunction?

PMID- 11338956
TI  - From protocol to pantogen and pantino: customizable surgical scripts with all the
      expert information.
AB  - Operative surgical training is handicapped by the lack of space and time of
      traditional training methods. This article reveals the extent and dangers of such
      constraints, and the benefits of surgical scripts with unlimited information,
      stored on a computer.

PMID- 11338957
TI  - Understanding sampling: representativeness matters.
AB  - Sampling, or selecting a group of people to represent a whole population, lies at
      the heart of almost all research designs. There are many ways of going about
      this, each of which presents its own problems. The trick is to obtain a good
      sized sample that is truly representative of the population as a whole.

PMID- 11338958
TI  - Thyrotoxicosis induced by alpha interferon therapy for hepatitis C.

PMID- 11338959
TI  - Postictal electrocardiographic changes mimicking acute myocardial infarction.

PMID- 11338960
TI  - Microangiopathic haemolytic anaemia in metastatic malignancy.

PMID- 11338961
TI  - Impaired renal function and cardiac troponin.

PMID- 11338962
TI  - Nasal septal perforation and oxygen cannulae.

PMID- 11338963
TI  - Oxford house: a review of research and implications for substance abuse recovery
      and community research.
AB  - After treatment for substance abuse, whether it is in hospital-based treatment
      programs, therapeutic communities, or recovery homes, many patients return to
      former high-risk environments or stressful family situations. Returning to these
      settings without a network of people to support abstinence increases chances of a
      relapse. As a consequence, substance abuse recidivism following treatment is high
      for both men and women. Alternative approaches need to be explored, and there are
      some promising types of recovery homes. From a public health perspective, a
      series of studies conducted at DePaul University suggests that one type of
      recovery home for alcohol abuse recovery has much potential. For example, within
      this self-help communal living setting, recovering alcoholics were able to
      maintain employment, thereby reducing their need for government subsidies.
      Maintaining employment for recovering alcoholics may promote increased personal
      responsibility, which may impact self-efficacy beliefs. These pilot studies,
      then, raised both theoretical and practical issues needing further evaluation.

PMID- 11338964
TI  - Adolescent substance use and family-based risk and protective factors: a
      literature review.
AB  - Adolescent substance use has become a serious concern nationwide. Although there
      are many ways of viewing adolescent substance use, family influence has been
      established as one of the strongest sources of risk and protection. A review of
      the literature indicated relevant theories for understanding adolescent substance
      use and specific family-based variables influencing adolescent substance use. In
      general, there seems to be a relationship between adolescent substance use and
      family-based risk and protective factors. Relevant theories identified in the
      literature review include family systems theory, social cognitive theory, social
      control theory, and strain theory. Specific family-based risk and protective
      factors include family relationships such as with siblings and parents and family
      characteristics such as ethnicity and religious backgrounds. Future implications
      for research and prevention/intervention in relation to family-based risk and
      protective factors are discussed.

PMID- 11338965
TI  - Preparing for the drug free years: session-specific effects of a universal parent
      training intervention with rural families.
AB  - Like their urban counterparts, adolescents from rural areas are at risk for
      health and behavior problems, including alcohol and other drug use. This study
      tested the effects on parenting practices of specific sessions of a parent
      training intervention, Preparing for the Drug Free Years, designed to prevent
      adolescent substance abuse and other problem behaviors. Two hundred and nine
      rural families were randomly assigned to an intervention or a wait-list control
      condition. Analyses of covariance comparing adjusted posttest scores revealed
      that parents in the intervention condition reported significant improvements in
      parenting behaviors targeted by specific intervention sessions when compared with
      controls. Effects were most pronounced among mothers. No significant effects were
      found for nontargeted parenting behaviors, and targeted behaviors were most
      improved among parents attending relevant program sessions. These results
      strengthen the internal validity of the study and increase the plausibility that
      reported improvements were due to the intervention.

PMID- 11338966
TI  - Evaluating skill acquisition in motivational interviewing: the development of an
      instrument to measure practice skills.
AB  - Social work education has long emphasized the need to provide competence-based
      education. However, little work has been done to identify, validate and evaluate
      competencies in specific fields such as addictions. The purpose of this study was
      to isolate a set of substance abuse intervention competencies using Motivational
      Interviewing that could be used to teach and evaluate students. The research
      proceeded in three stages. First, a modified Delphi approach involving social
      work practitioners was used to discern a set of positive and dysfunctional skills
      related to Motivational Interviewing. The primary researcher taught a graduate
      social work class aimed at teaching students theory and skills related to this
      model. Students demonstrated these skills with simulated clients through
      videotaped interviews. Finally, three observers rated the student interviews
      using this developed instrument. While inter-observer agreement was lower than
      anticipated, this study does provide early support for the development of
      competencies related to specific theoretical frameworks.

PMID- 11338967
TI  - Youth, drugs and resilience education.
AB  - Billions of dollars are spent annually on school-based drug education programs,
      with youthful drug use remaining near peak levels since the 1980s. Institutional,
      policy, and program evidence presented here suggests that although primarily
      delivered in schools, the educational community rarely participates in the
      development of drug education; and despite the finding that "no-use" programs
      such as Drug Abuse Resistance Education (D.A.R.E.) or Life-Skills Training (LST)
      are likely ineffective, they continue to thrive in schools. This may be explained
      by insufficient educational participation and scientific discourse considering
      these issues; and the role of interest group politics, such as the symbiotic
      relationship between government, researchers, and the tobacco industry, in drug
      education. In addition to this evidence, resilience based program alternatives,
      evaluation, and implications are discussed.

PMID- 11338968
TI  - [Frequency of Diphyllobothrium sp. infection in Argentine wild carnivores].
AB  - With the aims to determine the infection frequency by tapeworms of
      Diphyllobothrium genus 30 samples from captive wild carnivores were analyzed. A
      30% of the animal analyzed was positive to the infection. Whereas the family
      Procionidae has a high percentage of positivity (60%), Canidae have lower
      infection ratio (20-25%). The accuracy for the diagnosis of Diphylobothrium was
      made by the morphology of scolex, proglottids and eggs. This is the first report
      of the parasite presence in Argentine wild carnivores.

PMID- 11338969
TI  - [Description of the external morphology of Duboisiella proloba Baer, 1983
      (Trematoda: Strigeida) from Didelphis albiventris in argentina, by scanning
      electronic microscope].
AB  - The aim of this study was to report some external morphological features of
      Duboisiella proloba Baer, 1938. The parasites were collected during necropsy from
      the small intestine of Didelphis albiventris hunted in its native environment
      near Corrientes City, Argentina. Collected specimens of Duboisiella proloba were
      observed by light microscopy in order to be classified. Later the parasites were
      put into a 3% glutaraldehyde solution, dehydrated, dried by critical point,
      assembled, metallized, observed and photographed with a SEM. This is the first
      description of some external morphologic features of this species carried out by
      SEM in Argentina.

PMID- 11338970
TI  - A new parasite of the genus Cucullaus (Nematoda: Cucullanidae) from the fish
      Arius thalassinus (Ruppel).

PMID- 11338971
TI  - [Search for antibodies against Trichinella spiralis in free roaming rodents
      caught in a zoological park from Mexico City].
AB  - A serological survey to search for antibodies against T. spiralis was performed
      in free roaming rats (n = 64) and mice (n = 35) caught in a zoological park from
      Mexico City. Serum samples were analyzed by ELISA and immunoelectrotransfer blot
      assay (EIBT). None serum show positive absorbance values in ELISA nor recognized
      T. spiralis specific antigenic fractions in EIBT. However, two rat samples
      recognized three antigens of 31, 37 y 55 kDa, while one of them reacted with two
      additional antigens of 64 and 67 kDa. As it is known that the antigen epitope
      profiles varied among Trichinella species, it could be possible that in rats,
      there is 3% of antibody prevalence against Trichinella sp.; however, due that
      other organisms could induce the production of cross-reacting antibodies, such
      conclusion can not be supported at all. These results suggest that T. spiralis
      was not part of helminthological fauna in these rodents.

PMID- 11338972
TI  - The soil-transmitted parasitic zoonoses.

PMID- 11338973
TI  - Control program of hydatid disease in the province of Rio Negro Argentina. 1980
      1997.

PMID- 11338974
TI  - [Epidemiology of human hydatidosis in the IX Region of la Araucania, Chile 1991
      1998].
AB  - In the region of la Araucania, located in the south of Chile (37 degrees 24'-39
      degrees 34' South lat.), the economy is based in cattle raising and agriculture.
      The cases of human hydatidosis, mortality and notification registered in la
      Araucania 1991-1998 are reviewed. The rate for hydatid disease is 38.5 per
      100,000 population. Liver (47.1%) and lung (40.7%) were the most affected
      viscera. Days in hospital, 11-20 the 56.1%. Disease in female is 51.1%. The
      mortality rate is 0.8 per 100,000, the most frequently affected county is
      Imperial. The age group 15-44 years is the most affected. The notification rate
      is 8.74 per 100,000 population. The rate for hydatid disease is higher than the
      rate of notification, then necessarily there exist a subnotification. We think
      that it is necessary to investigate the serological prevalence of hydatidosis in
      the population of the IX Region Araucania.

PMID- 11338975
TI  - [Host parasite relationship among 3 Schistosoma mansoni and 6 Biomphalaria
      glabrata strains from epidemic and no epidemic Venezuelan areas is studied].
AB  - Six lots of 18 B. glabrata from: La Victoria, Turmero, Cagua in Aragua state;
      Caserio El 25 in Carabobo state, Chabasquen in Portuguesa state and Humocaro Bajo
      in Lara state, were experimentally infected with miracidia of SM, C5 and C6
      strains of Schistosoma mansoni (18 snails/Schistosoma mansoni strain). The
      averages of the intramolluscal period (IMP) obtained for the S. mansoni strains
      were very similar and comprised between 35.4 and 36.1 days. No significative
      statistical differences in the IMP were found according to the S. mansoni strain
      and the size of snails: < 7 mm and > 7 mm. However, significative statistical
      differences in the IMP were found, in relation to the B. glabrata strain and
      between the snails classified in two groups according to the S. mansoni dose (5
      miracidia/snail and 10 miracidia/snail). The higher percentages of infection (PI)
      were found for the following parasite-snail combinations: C6-Cas. El 25 (80.7%),
      SM-La Victoria (73.1%) and C5-Cagua (62%). No significative statistical
      differences were found for the PI a) between the snail classified in two groups
      according to the size (< 7 mm and > 7 mm), b) in relation to the miracidium
      dosification (5 and 10 miracidia/snail and c) in accord to the S. mansoni strain.
      However, significative statistical differences were found for the PI obtained
      with different strains of the snail.

PMID- 11338976
TI  - [Scapular hydatidosis with extraosseous involvement].
AB  - A forty three-year-old female, born in a rural area of southern Chile, at the age
      of 30 presented pain and limitation of motility of the right shoulder. Later on,
      she presented an increasing of volume at the right scapular region. A radiography
      showed an osteolytic lesion of the scapula. In a biopsy an osseous hydatidosis
      was found and a hydatid cyst was extirpated from the soft tissues. Four years
      later, as she presented again pain and volume increasing in the same anatomical
      area, albendazole was given to her, and a CAT practiced revealed osteolytic
      lesions of the bone, several periosteal ruptures and multiple cysts in the
      muscles. She was submitted to surgery again in order to extirpate cysts. After
      two years the patient presented the same clinical manifestations and radiological
      and CAT images previously observed. In considering all these facts a radical
      surgery was decided.

PMID- 11338977
TI  - [Parasitology and entomology in the 29th century in Latin American narrative].
AB  - In the present review of twelve pieces produced by distinguished 20th century
      Latin American writers--Jorge Luis Borges from Argentina, Jorge Amado and Joao
      Ubaldo Ribeiro from Brazil, Jose Donoso from Chile, Gabriel Garcia Marquez from
      Colombia, Alejo Carpentier from Cuba, Miguel Angel Asturias from Guatemala,
      Octavio Paz from Mexico, Mario Vargas Llosa from Peru, Horacio Quiroga and Mario
      Benedetti from Uruguay and Arturo Uslar-Pietri from Venezuela--paragraphs or
      parts of paragraphs in which parasitological or entomological situations of the
      most varied hues are referred to or described, have been extracted in a selective
      form. Sometimes in these descriptions appear, local or regional expressions,
      without ignoring colorful folklore representations. For a easier interpretation
      these or part of these paragraph sentences have been arranged by thematic
      similarities. In a varied and kaleidoscopic vision, it will be possible to find
      protozoiasis (malaria, Chagas disease, leishmaniasis, amebiasis), helminthiases
      (ascariasis, hydatidosis, trichinosis, schistosomiasis, cysticercosis,
      onchocerciasis), parasitoses produced by arthropods (pediculosis, scabies,
      tungiasis, myiasis), passing progressively to hemaphagous arthropods (mosquitoes,
      gnats, horse flies, bedbugs, ticks), venomous arthropods (Latrodectus spiders,
      scorpions, wasps, bees), mechanical vectors (flies and cockroaches), culminating
      with a conjunction of bucolic arthropods (butterflies, crickets, grasshoppers
      cicadas, ants, centipedes, beetles, glow worms, dragonflies).

PMID- 11338978
TI  - [Contamination by helminths in public places of the province of Chubut,
      Argentina].
AB  - Canine-borne helminthiases constitute a worldwide problem. Some of these
      parasites can originate serious pathologies in humans. Given the potential
      existence of these zoonoses in Argentina, horizontal surveys on contamination
      degree evaluated as faeces per hectare and on parasite prevalence in faeces were
      carried out in six localities of the Province of Chubut. The behaviour of people
      visiting public places was also analyzed qualitatively. All of the survey sites
      were contaminated with faeces and with some parasitic forms. Contamination
      degrees ranged from 32 to 147 faeces/ha. Toxocara sp. (17.4%), Strongyloides sp.
      (5.1%), and Ancylostoma. sp (5.6%) were the main genera among other parasites
      detected. As a whole, the analysis revealed that contamination degree, prevalence
      and human behaviour in relation to the exposure to the parasite would be the main
      factors to be taken into account in formulating control measures. Transmission
      risk patterns in Chubut were not homogeneous; therefore, studies and control
      strategies should be devised and implemented at the local scale.

PMID- 11338979
TI  - [Soil contamination with Toxocara sp. eggs in squares and public places from the
      city of La Plata. Buenos Aires, Argentina].
AB  - This study consisted of a stratified sampling, randomly taken, of the soil from
      the squares and parks of the city of La Plata, Province of Buenos Aires, in order
      to establish the prevalence of contamination caused by Toxocara sp. A total 242
      soil samples was examined. From each sample a 10 grams aliquot was taken, washed
      in a 0.2% Tween 80 solution, and processed using the technique of concentration
      by flotation with sugar solution. There was a prevalence of 13.2%. In each
      positive sample, the quantity of eggs varied from 1 to 4. Toxocara sp. eggs were
      observed in 15 out of 22 squares and parks investigated. The sampling design and
      the processing method employed were satisfactory for the recovering and
      identification of Toxocara sp. eggs.

PMID- 11338980
TI  - [Environmental contamination with Toxocara sp. eggs in public squares and parks
      from Santiago, Chile, 1999].
AB  - Most of cases of visceral larva migrans syndrome are caused by Toxocara canis
      larvae. Man acquires the infection by accidental ingestion of ripe eggs of the
      helminth. In order to find out the frequency of the presence of Toxocara sp. eggs
      in dog fecal specimens from public places of Santiago city in 1999 july-september
      a study was carried out in 84 squares and 12 parks from 32 counties. Three fecal
      samples were collected in each of these places, making a total of 288. Each
      sample was processed according to a modified Telemann method and three smears of
      each were microscopically examined. Toxocara sp. eggs were found in 39 (13.5%)
      fecal specimens. In 28/84 (33.3%) squares and in 8/12 (66.7%) parks these eggs
      were detected. These results make necessary the control of dogs and cats
      populations with the aim of reduce the presence of animals without responsible
      owners. It should be advisable to prevent dogs and cats defecation in public
      areas grounds, trying to exclude these animals from recreation areas.

PMID- 11338981
TI  - Intestinal nematodes of stray dogs as zoonoses agents in D. Pedrito city (RS
      Brazil).

PMID- 11338982
TI  - [Frequency of anti-Toxoplasma gondii antibodies in cats from Valdivia city,
      Chile].
AB  - Toxoplasmosis is a parasitic zoonosis. The importance of the cat as related to
      this parasitosis lies in the fact that it is not only the definite host of the
      parasite, but responsible for its dissemination through the release of oocysts,
      which subsequently infect both humans and other animals. The objective of this
      study was to determine the serological prevalence of Toxoplasma gondii in the
      feline population of the city of Valdivia (Chile) and to establish the possible
      epidemiological implications of this prevalence. With these goals in mind the
      technique of indirect immunofluorescence was implemented to detect anti- T.
      gondii species--specific IgG. Blood samples from 97 cats (selected using a
      directed sampling process) from different sectors of Valdivia were collected. The
      sample included 46 males and 51 females of different ages, Positive and negative
      control sera obtained from de United States were used to verify the results,
      observed by UV microscopy. The anti-feline IgG antibody was used as directed by
      the manufacturer (Sigma). Of the 97 selected cats, 32 were found to be positive
      with a titre higher than 1:4, a prevalence of 33.0%. The number of infected males
      as compared to the number of infected females was found to be statistically
      insignificant, using the chi-square analysis with p less than 0.1. In contrast, a
      definite correlation between age and seropositivity was found; infection levels
      were higher in older animals. These results are consistent with those obtained in
      different studies on this topic that have been performed in different parts of
      the world. However, they would seem to be in conflict with other, similar studies
      that have been done recently in Chile; this may be due to the fact that the cats
      selected for this study were exposed to different climatic conditions than those
      examined in previous works. In conclusion, it has been determined that in
      Valdivia exist cats infected by T. gondii, which indicate the presence of the
      necessary epidemiological conditions for the persistence of this parasitic cycle
      and the source of infection for humans and other animals.

PMID- 11338983
TI  - Cholera vaccines.

PMID- 11338984
TI  - "Where work is play for mortal stakes": the good hour in child analysis.
AB  - To explore the concept of the "good hour" in child analysis I discuss an hour in
      the analysis of a six-and-a-half-year-old girl. Elements of this hour include a
      palpable therapeutic alliance, affective immediacy, surprise, and discovery,
      oscillating therapeutic action of action, play, and verbalization, creative
      accessibility to the unconscious, the transference, the countertransference, and
      a capacity to work with conflict, defense, and fantasy. These qualities are
      similar to those described by Kris for adult analysis over forty years ago. The
      present hour, however, illustrates greater emphasis on affect rather than drive,
      the therapeutic action of play in the analytic setting, and the transformative
      importance of the relationship. In addition, the hour highlights a greater focus
      on communication by action and enactment, the highly informative uses of the
      countertransference, and the co-creation of the analytic process.

PMID- 11338985
TI  - A "good hour" in child analysis and adult analysis.
AB  - An attempt is made to compare and contrast a "good hour" in child and adult
      psychoanalysis. Since all analytic hours reflect the conflicted vicissitudes of
      an associative process, what function can it serve to isolate certain specific
      hours as "good"? While analytic process always reflects the simultaneous impulse
      to reveal and to conceal, it is argued that at times the mind "surprises" itself
      with its own daring and savors the epiphany before the forces of defense make off
      with it again. A child's surprising formulation of the nature of transference and
      therapeutic alliance is compared to an adult's more mature grasp and use of the
      same concept. Analysis and creativity are compared as activities that nourish and
      foster surprise elements, creating new stabilities out of their tolerance for
      instability and destabilization. Childhood is emphasized as the crucible par
      excellence where surprises are not only engendered but integrated. Child analysis
      may be more accustomed to surprises and perhaps can contribute to adult analytic
      experience by way of this unusual expertise. The elements of surprise in certain
      analytic hours are discussed in terms of their developmental psychoanalytic
      components. Hours can be termed "good" as long as the implication that more
      defensive hours are "bad" is resisted with the psychoanalytic conviction that the
      mind reflects the human condition and that therefore nothing human is alien to
      it. As Shakespeare put it, there is nothing either good or bad but thinking makes
      it so!

PMID- 11338986
TI  - Little orphan Anastasia. The analysis of an adopted Russian girl.
AB  - It is becoming commonplace for analysts to hear about or encounter in their
      clinical work adopted children from Korea, China, Eastern Europe, or Russia.
      There is wide variation in the orphanage experience from one area to another and
      also in the manner in which the transitional phase from orphanage to adoptive
      parents is carried out. Not surprisingly, the experience of being an orphan
      carries with it lifelong implications and repercussions, particularly in the area
      of self/object relations. Some of the problems of being an orphan are obvious at
      the time of adoption. Others unfold only in the course of subsequent development.
      We are increasingly called upon to assist adoptive families whose children are
      struggling amid much pain and confusion with the aftermath of the threefold
      experience of becoming an orphan, being raised in an orphanage, and joining a
      family of another culture. This essay describes in some detail the infancy and
      early childhood of "Little Orphan Anastasia" as she picks through the emotional
      rubble of her infancy and samples the embarrassment of rich nurture in her
      current life with her adoptive parents, the Carters. This is followed by a
      description of the opening phase of her analysis, in which I sketch some of her
      attempts to fashion an adapted identity that is more congruent with her life
      before and after her adoption.

PMID- 11338987
TI  - The development and consequences of an aggressive symbiotic fantasy.
AB  - Chronic anxiety in a female patient was understood to have multiple meanings in
      relating to the mother through the fantasy of a symbiotic union. The origins of
      the fantasy are traced to the patient's poor relationship with a preoccupied and
      unavailable mother. The fantasy underwent several transformations under the
      influence of subsequent developmental phases and the special role of aggression
      in its elaboration. This paper illustrates the reciprocal interactions between
      separation-individuation and psychosexual development and their influence on the
      development of the self and gender identity, defenses against aggression,
      development of a sadomasochistic style, and transference-countertransference
      interactions. The symbiotic fantasy is seen as carrying the imprints of all
      developmental phases and as having multiple functions.

PMID- 11338988
TI  - The wooden shell. The legend as representative of the early stage of development.
AB  - Legends serve as an important means of expressing fears, wishes, and fantasies.
      One of the best known and beloved legends worldwide is the nineteenth-century
      tale of Pinocchio, the wooden puppet who becomes a "real boy," or, as eventually
      becomes apparent, the boy enclosed in a wooden shell. This protective shell is an
      extremely interesting symbol and may be the reason the story holds a special
      place in the human experience. This paper discusses the significance of the
      wooden shell in the early protection of the developing psyche against invasive
      stimuli. In cases of normal development, this rigid enclosure is eventually
      discarded as the psyche matures. However, in pathological situations, it may
      remain a static, inhibitive shield. We describe the case of O., whose shell
      prevented his healthy interaction with the environment, and discuss how his
      problem was managed in the context of the legend. We also discuss related
      theories of the envelope of the ego.

PMID- 11338989
TI  - Knowing and not knowing. Some thoughts about insight.
AB  - This paper examines the concept of insight from the point of view that insight is
      about knowing. As a process it is how one comes to know, and as a construct it is
      what becomes known. Utilizing detailed clinical material from the analysis of a
      young girl, the paper approaches this issue by asking. How did Amy go about
      knowing? The multifaceted analytic relationship, the dimensions of change, and
      the analyst's technique are highlighted.

PMID- 11338990
TI  - Michael--psychotherapeutic treatment in the context of residential treatment.
AB  - This paper describes the five-year psychotherapy of a boy suffering from a very
      early developmental disorder. The treatment involved bringing the child back to
      the point of crisis in maternal caring. This type of regression is vital in
      treating certain severe disturbances, but it can also be dangerous; hence the
      importance of an appropriate environmental space. The treatment milieu has to be
      both a "holding" environment and a "containing" one, for child and therapist
      alike. Residential treatment based on a continuity of transitional spaces
      provided such an environment for Michael and helped nurture his emotional growth.

PMID- 11338991
TI  - Recovery and adaptation.
AB  - Recovery and adaptation go hand in hand. The potential for recovery and
      adaptation is present in each child and adult. It is through psychoanalytic
      understanding that the strategies for reaching these potentials can be activated,
      coordinated, and understood.

PMID- 11338992
TI  - On hatred. With comments on the revolutionary, the saint, and the terrorist.
AB  - It is common to base an assessment of psychological health on an individual's
      ability to love. However, the ability to hate is no less important a
      manifestation of the healthy personality. The author investigates the psychology
      of hatred and the possible effects of psychoanalytic treatment on the development
      of the capacity to hate and, by extension, to engage in revolutionary political
      activity.

PMID- 11338993
TI  - At the sources of the symbolization process. The psychoanalyst as an observer of
      early trauma.
AB  - This paper presents a psychoanalytic study of mothers and infants, concentrating
      on very early traumatization and its impact on the symbolization process. This
      can be traced in the analysis in the destruction of freedom of association and
      the symbolization process, leading to petrifications, somatizations, or acting
      out. A theory of the origin of the symbolization process is developed by
      observing the kinesthesia of traumatized infants. This approach, based on years
      of observation, offers a perspective on the landscape before representation,
      before the object has become represented. The theory takes account of forces from
      the area of the unconscious as described in "Beyond the Pleasure Principle"
      (Freud, 1920). A new view of the complexity and multi-dimensionality of the mind
      emerges from this study. The author tries to demonstrate that the mind is multi
      dimensional and that our theory of the mind therefore needs the complexity of
      UCS/PRC/CS. If psychoanalytic theorizing is to remain faithful to the forms and
      movements of the associative mind, it should not be simplified into linear
      causalities, as it would be if we were concerned only with object
      representations.

PMID- 11338994
TI  - The replacement child. Variations on a theme in history and psychoanalysis.
AB  - This paper reviews the literature on the replacement child syndrome and examines
      its historical, theoretical, and biographical ramifications. Although a
      replacement child in a literal sense is one conceived to take the place of a
      deceased sibling, the concept may be extended to many other situations in which a
      child is put in the place of someone else in the family system. In his experience
      of survivor guilt for his deceased brother Julius, Freud may be regarded as such
      a metaphorical replacement child. The collective tragedy of the Holocaust gives
      the replacement child concept a special meaning, since the children born in its
      aftermath had to fill the void in the lives not only of individual parents but of
      the Jewish people as a whole. One of the coauthors of this paper, Leon Anisfeld,
      was born after World War II to parents who had lost previous spouses and
      children, and his personal experience as a replacement child informs the
      theoretical issues considered here.

PMID- 11338995
TI  - Kolya. Antiphonal development between adult and child.
AB  - The film Kolya (1996) directed by Jan Sverak, illustrates the antiphonal calling
      and answering development between man and boy who are both thrown and drawn
      together. Amid the larger context of the "Velvet Revolution" in Czechoslovakia,
      each supports the quieter revolution in the development of the other. The
      intraplay and interplay deepen with consideration of the father-son collaboration
      between director (son) and playwright-actor (father) which gave rise to this
      remarkable picture.

PMID- 11338996
TI  - Parapraxes in the plays of William Shakespeare.
AB  - Parapraxes in the psychopathology of everyday life are "mistakes" that reveal the
      workings of the unconscious. (Obviously they existed before Freud's time, but it
      was Freud who gave them a name and dissected their complex psychological
      meanings.) When they occur in a great work of art (as in Shakespeare's plays)
      they are obviously not "mistakes" at all but carefully planted details of the
      artist's over-all aesthetic conception. Just as fictional dreams, as in Jensen's
      Gradiva, seem to follow the rules of nocturnal dream process and can be subjected
      to psychoanalytic scrutiny, fictional parapraxes are doubly interesting because
      they not only express the inwardness of a protagonist but reveal something of the
      writer's aesthetic method as well. This paper attempts to address these double
      points of entry into the mystery of Shakespeare's plays, posing the question,
      "Can the seemingly trivial or irrelevant (a handful of parapraxes in 38 plays)
      shed any light on the most complex characters in Western literature and the
      extraordinary mind of their creator?"

PMID- 11338997
TI  - Pictures into words. Visual models and data in psychoanalysis.
AB  - The psychoanalytic method is considered as an instrument or medium of
      observation, with attention to certain peculiarities of data collection and
      recording. Freud's visual models and metaphors are then reviewed. Subsequent
      approaches to visual data in analysis are examined in the work of Charles Fisher,
      Mark Kanzer, Bertram Lewin, and M. Robert Gardner. A corresponding theory of
      therapeutic action is suggested.

PMID- 11338998
TI  - In memoriam: Dr. K. R. Eissler, 1908-1999.

PMID- 11338999
TI  - K. R. Eissler: a selected bibliography.

PMID- 11339000
TI  - Aichhorn revisited.
AB  - August Aichhorn first published Wayward Youth in German in 1925. His willingness
      to approach a problem as difficult as delinquency in terms of psychoanalytic
      theory and to then test his theories with groups of delinquents in a reformatory
      setting were truly pioneering. Perhaps his greatest success as an educator was in
      attracting other psychoanalytic leaders, most notably Sigmund Freud and Kurt
      Eissler, to extol and extend his early efforts. The turn of the century seems a
      fitting time to revisit Aichhorn's views, to assess his impact on colleagues, and
      to place his contribution in the perspective of current research and practices.

PMID- 11339001
TI  - "That's what my imagination says." A study of antisocial behavior in two boys.
AB  - Children attempt to negotiate a balance between aggressive urges and moral
      imperatives in order to protect both themselves and those they love. They must
      also balance pleasure associated with the reality and fantasy of vanquishing
      competitors and the dangers of anticipated retaliation. Psychoanalytic work with
      anti-social and violent young patients affords a special opportunity to explore
      how the failures in these negotiations can lead to seriously limited and
      distorted views of self and others. The treatments of Rick, age 8, and Dean, age
      16, demonstrate the ways in which dangerous and frightening aspects of enduring
      psychic reality dictate configurations of both aggressive fantasy and action.
      Clinical inquiry revealed how each boy's longings, defenses and conflicts found
      expression in the attacking, destroying, and confrontations of daily life.

PMID- 11339002
TI  - Living in history and ego strength.
AB  - From his observations as a member of the U.S. Armed Forces during World War II,
      the author examines the relationship between the ability to form constructive
      historical identifications--to "live in history"--and ego strength. He surmises
      that the American soldier's failure to draw upon such identifications represents
      an ego weakness that resulted in a greater frequency and intensity of
      psychopathology during the war.

PMID- 11339003
TI  - Gustav Mahler's choice. A note on adolescence, genius, and psychosomatics.
AB  - At a time of crisis in his marital life, Gustav Mahler met with Freud. After the
      meeting with Freud, Mahler's spirits and sexual potency were restored, and his
      attitude toward his wife changed remarkably. However, these changes were
      accompanied by an apparent loss of the ability to compose: there is no evidence
      that Mahler wrote any new music between the summer of 1910, when he saw Freud,
      and May of 1911, when he died from complications of streptococcal endocarditis.
      Mahler in effect had chosen human love over artistic creativity. An analysis of
      the encounter and its effects on the composer's artistic capabilities raises
      questions about the psychology of genius, adolescent trauma, and psychosomatics.

PMID- 11339004
TI  - Genetics and rheumatic diseases: rheumatoid arthritis and ankylosing spondylitis.
      The genetics of rheumatoid arthritis.

PMID- 11339005
TI  - The genetics of ankylosing spondylitis.

PMID- 11339006
TI  - [The effect of aging on the activity of the autonomic nervous system in long
      distance runners].
AB  - The aim of the study was to evaluate the effect of endurance physical training on
      the autonomic function in runners. The study was performed on 20 long distance
      runners, divided into two groups. The first group of runners contained 12 young
      men of age of 20-24 years (age 21.75 +/- 1.4 years: mean S.D.--standard
      deviation). Into the second group 9 experienced runners, who practice long
      distance running for over 40 years, were qualified. The mean age of those runners
      was 52.9 +/- 7.2 years. Moreover two control groups, matched for age and gender
      were recruited. One of them was made up of 12 healthy volunteers (age 21.6 +/-
      1.23 years), the second contained 9 men (age 52.9 +/- 7.2 years). In this study,
      the measurement of the cardiac autonomic nervous system, using the HRV computer
      assisted programme (Proster, Poland), was performed. The characteristics of the
      HRV (heart rate variability) were estimated. We have observed, that the RR
      intervals in runners were longer than in healthy volunteers (1033.5 +/- 185.4 ms
      vs. 888.1 +/- 115.3 ms. p < 0.01). We have observed a tendency towards increasing
      of the RR intervals with the increase of age, of the tested person, as well. A
      reverse tendency, a shortening of the RR intervals with ageing, was observed in
      the control groups. The standard deviation of the RR intervals in runners was
      higher than in the control group (p < 0.05). In the young runners we noticed the
      prevalence of parasympathetic activity, expressed by the HF (high frequency)
      spectra (875.7 ms2 vs. 816.7 ms2) in comparison with the healthy individuals. In
      the old runners the prevalence of sympathetic activity, expressed by LF (low
      frequency) spectra (1088.75 ms2 vs. 220.1 ms2, p < 0.05) and parasympathetic
      activity (920.38 ms2 vs. 294.25 ms2) in comparison with the control group, was
      observed. It was expressed by the increase of the LF/HF ratio (0.75 vs. 2.1). The
      results of our study indicate, that the autonomic, particularly sympathetic,
      activity in sportsmen is not affected by ageing up to the sixth decade of life.

PMID- 11339007
TI  - [Ultrasonographic evaluation of thyroid tissue perfusion in patients with Graves
      Basedow disease as preparation for surgery].
AB  - The aim of this work was to asses the usefulness of a new colour Doppler
      ultrasonography technique, namely power Doppler (PD), in the management of
      thyroid tissue perfusion in patients with Graves' disease before surgery. Forty
      six patients with Graves' disease treated conventionally with Lugol's solution
      before the operation were examined with power-Doppler scanner. The distribution
      of the vascular patterns of both lobes was analysed by computer program. Results
      were compared with bleeding during surgery subjectively and objectively. The
      analysis of power-Doppler thyroid perfusion showed significantly higher values of
      blood flow in patients suffering from Graves disease when compared with control
      group. Pre-operative preparation with Lugol's iodine decreases parenchymal blood
      flow. Auscultation of vascular murmur over the gland fading after Lugol's
      treatment does not always reflect parenchymal high value of blood flow measured
      by density of microvessels.

PMID- 11339009
TI  - Immediate effects of endoscopic sphincterotomy on sphincter of Oddi motility.
AB  - The evidence exists that incomplete sphincterotomy in patients with biliary tract
      diseases may result in early symptoms reoccurrence or lack of improvement.
      Sphincter of Oddi manometry (SOM) can be used to verify the completeness of the
      procedure. The purpose of the study was to investigate the immediate effects of
      biliary endoscopic sphincterotomy (BES) and common bile duct stones (CBDS)
      clearance on biliary sphincter of Oddi (SO) motility. Moreover the percentage of
      incomplete sphincterotomies was estimated. 26 patients (6 male, 20 female, 24-93
      years) with confirmed choledocholithiasis were investigated. All underwent BES
      followed by CBDS extraction, and then SO manometry (SOM) was performed. Moreover
      6 patients underwent SOM prior to BES. SOM was performed with a triple lumen 5 Fr
      catheter attached to the water perfused low compliance system. Immediately after
      sphincterotomy and extraction of the CBDS common bile duct pressure dropped from
      a mean of 10.9 mmHg to 2.9 mmHg (p < 0.05). Similarly basal biliary sphincter
      pressure decreased from 22.7 mmHg to 7.3 mmHg (p < 0.05). 20 patients presented
      duodeno-choledochal gradient of less than 5 mmHg. However only 10 patients had
      also basal sphincter pressure lower than 5 mmHg. The phasic sphincter activity
      was abolished in 16 patients, whereas phasic contractions persisted in 10
      patients. Seven patients displayed uncoordinated, low amplitude contractility.
      BES significantly decreases SO and CBD pressures, but when performed for CBDS
      extraction, commonly does not abolish SO motor activity nor ablate choledocho
      duodenal gradient. Therefore to confirm the completeness of sphincterotomy, SO
      manometry is recommended.

PMID- 11339008
TI  - [The effect of chronic alcohol use on heart rate variability].
AB  - A long lasting alcohol intake causes, amongst numerous systemic damages, also the
      autonomic nervous system (ANS) dysfunction, which causes the autonomic heart rate
      regulation disorders. The aim of the study was to evaluate the autonomic
      regulation of the circulation in chronic alcoholism. Seventeen alcoholics, 24-55
      years of age (mean 43 +/- 5.2 years) were examined. They have been abstainers for
      2-6 years. The cardiac ANS function was evaluated using the HRV measurement. The
      HRV was registered using V6 EKG lead. The recording was performed through the 15
      min of resting conditions and 5 min of the deep breathing test. A group
      containing healthy volunteers, matched for age and gender, for the comparison of
      the HRV results was recruited. In the examined group, during the resting
      conditions, the significant RR period changes weren't observed (999.7 +/- 139.2
      vs. 967 +/- 144.9; p > 0.05). The nonsignificant lower values of the spectral
      analysis parameters of HRV: LF (954.1 +/- 1162.6 vs. 1456.4 +/- 1327.1; p > 0.05)
      and HF (676.4 +/- 414.2 vs. 1557 +/- 1854.4; p > 0.05) and LF/HF ratio (1.5 +/-
      1.14 vs. 1.38 +/- 1.28; p > 0.05) were also noticed. In response to the DB test,
      the mean value of the RR period wasn't significantly changed (921.4 +/- 152.3 vs.
      930.6 +/- 137.8; p > 0.05). In DB test the significant decrease of LF (3465.8 +/-
      2750.1 vs. 11558.6 +/- 7902.5; p < 0.001) and HF (406.1 +/- 366.8 vs. 1665 +/-
      1757.1; p < 0.01) was observed. No significant change of LF/HF mean ratio (11.6
      +/- 6.97 vs. 14.7 +/- 11.6; p > 0.05) was noticed. The results of our study
      indicate on the maintenance of the HRV disorders in chronic alcoholics, during
      the abstinence.

PMID- 11339010
TI  - [Measurement of vascular density in proliferative lesions of the thyroid gland].
AB  - In the present study vascular density was measure in histopathological slides of
      the simple goiter (15 cases) and of the same proliferative condition of the
      thyroid gland (113 cases) including adenoma (29 cases) and carcinoma (16 cases).
      Epithelial antibody CD31 and vWF identified vessels with the help of
      semiautomatic image analysis system. It has been shown that the highest values
      were typical for neoplastic tumors. However significant overlap has been shown.
      Statistically significant differences were very weakly seen between neoplasm's
      and thyroid hyperfunction. Also differences between carcinomas and adenomas were
      of low significance. Probably this is because of great heterogeneity of
      carcinomatosus neoplasms included in this study. Unexpectedly there were also no
      statistically significant differences between simple goiter, hyperplasia and
      thyroid hyperfunction.

PMID- 11339011
TI  - [Oxidative stress in Alzheimer's disease].
AB  - A short review of recent literature on oxidative stress in Alzheimer's disease is
      presented. Own results on the content of reduced glutathione and protein-bound
      sulfhydryl groups in the blood of Alzheimer's disease patients are reported. In
      comparison with a group of healthy age-matched controls the Alzheimer's disease
      patients have a decreased level of reduced glutathione in erythocytes and
      significantly increased amounts of protein-bound sulfhydryl groups in blood
      plasma.

PMID- 11339012
TI  - [Evaluation of magnesium cation levels in serum of patients with mitral valve
      prolapse syndrome].
AB  - Magnesium deficiency has been suggested to be related to the mitral valve
      prolapse syndrome (MVPS). The aim of the present study was to analyse the
      concentration of magnesium in blood plasma of patients (pts) with MVPS. In the
      group of 80 subjects, including 50 pts with MVPS and 30 healthy people matched
      for age and gender, who comprised the control group (CG), concentration of
      magnesium in blood plasma was estimated. Magnesium levels were measured by atomic
      absorption spectrophotometry. Mean concentration of magnesium cation in plasma in
      pts with MVPS was 0.74 +/- 0.12 mmol/l (range 0.47-1.02 mmol/l). It was only
      1.02% lower than in the CG (x = 0.76 +/- 0.07 mmol/l; range 0.67-0.97 mmol/l).
      However evaluation of the magnesium concentration in blood plasma did not prove
      magnesium deficiency in the mitral valve prolapse syndrome. Moreover the study
      revealed that histograms of magnesium concentration values in both investigated
      groups were divergent.

PMID- 11339013
TI  - [Population based studies on the incidence of chronic respiratory symptoms and
      lung function in children from Krakow].
AB  - The epidemiologic study has been carried out in the sample of 1048 schoolchildren
      at the age of 11 years in order to assess the impact of various chronic
      respiratory symptoms on lung function. The symptoms included chronic dry cough,
      chronic phlegm, attacks of cough at nights, breathlessness, wheezing independent
      from respiratory infections or colds, attacks of wheezing at nights, and attacks
      of dyspnea with wheezing. Lung function was measured by the following spirometric
      indices: FEV1/FVC%, FEV1, FEF25-75% and PEFR. Multiple regression analysis showed
      strong statistical inverse relationship between FEV1/FVC% and FEF25-75% and
      attacks of wheezing at night and attacks of dyspnea with wheezing or asthma
      diagnosed by physician. The separate analysis performed in the subsample of
      children without asthma and asthmatic symptoms (attacks of wheezing at night and
      attacks of dyspnea with wheezing) found out that only chronic dry cough was
      related significantly to the lower values of FEV1 and PEFR in the children.

PMID- 11339014
TI  - [Use of polymerase chain reaction (PCR) for detection of tick Borrelia
      burgdorferi sensulato in screening studies].
AB  - Within the last few years, the incidence of Lyme disease has rapidly increased in
      Europe, with the causative agent of the disease is Borrelia burgdorferi--a
      spirochete. In Poland, Lyme borreliosis is being identified, mainly, based on the
      clinical symptoms, epidemiological anamnesis, and serological tests. On the other
      hand, it is evident from the foreign publications, that in many cases
      representing different phases of Lyme disease, a reliable and totally accurate
      identification tool of Borrelia burgdorferi is amplification of bacterial DNA
      using PCR method. The main goal of the present studies has been implementation of
      the DNA amplification method into diagnostic procedures of Lyme. Although we
      dealt with DNA of B. burgdorferi isolated from tics, it would not make a
      difference because the method of DNA isolation is the same for human samples. The
      results acquired from the preliminary studies, suggest that amplification of a
      fragment of fla gene, may be useful in Lyme disease diagnostics. Spirochetes of
      B. burgdorferi sensu lato were detected in tics Ixodes ricinus using PCR method
      in both individual animals and tick pools. The latter version of the method seems
      to be very useful in so called screening studies, because of minimizing the cost
      and duration of the procedure.

PMID- 11339015
TI  - [Tumors of borderline malignancy or atypical proliferative tumors of the ovary?].
AB  - Nearly sixty years have passed since Taylor first published the concept of
      ovarian epithelial semimalignant tumors. After confirmation of this suggestion by
      FIGO and WHO these tumors became the subject of analyses which helped to separate
      unfavourable prognostic cases in this group. We would like to present a
      description of basic and latest papers on borderline ovarian tumors.

PMID- 11339016
TI  - [The effect of anthocyanin dye from grapes on experimental diabetes].
AB  - In the work an effect of anthocyanins of red wine type Cabernet on the course and
      intensity of symptoms of the experimental diabetes in the rats has been examined.
      The estimation of the course of experimental diabetes was based on: determination
      of sugar concentration in urine and blood serum, determination of concentration
      of the unsaturated fatty acids peroxidation in urine and blood serum, also on the
      change of body mass during the experiment. The examination was carried out on 80,
      weighing 200-250 g, rats. They lived in the animal quarters with a stable
      temperature and humidity being fed with standard fodder (Murigan) with water
      supply in ever quantity. The rats were divided into the following four group: I-
      control group, II--group of animals receiving intraperitoneal streptozotocin in
      concentration 70 mg/kg m.c., III--group of animals receiving intragastric 10
      mg/kg m.c. of natural anthocyanin dye of red wine type Cabernet, IV--group of
      animals receiving intraperitoneal 70 mg/kg m.c. of streptozotocin and
      simultaneously receiving intragastric 1 mg/kg m.c. of natural anthocyanin dye. An
      essential increase of glucose concentration in urine was found in the rats after
      streptozotocin injection. A simultaneous daily administration of anthocyanins
      obtained from red wine type Cabernet and streptozotocin substantially decreased
      sugar concentration in urine and blood serum. Those anthocyanins also inhibited
      loss of body mass caused by the former injection of streptozotocin.
      Simultaneously antocyan pigment was stated to considerably prevent generation of
      free oxygen radicals. The decrease of peroxidation of lipids, the measure of
      which was lowering of the concentration of the products of unsaturated fatty
      acids oxidation in urine and blood serum was also observed.

PMID- 11339017
TI  - [Speech visualization for evaluation of iatrogenic recurrent laryngeal nerve
      injuries].
AB  - A study was conducted to investigate the intra operative laryngeal recurrent
      nerve injury and subsequent vocal disturbances. The recovery of voice condition
      in group of 20 patients with unilateral laryngeal nerve injury was examined by
      the whole range of both presurgical and postsurgical tests. Patients were
      selected from a group a 1867 surgical treated in 3-rd Department of Surgery
      Jagiellonian University School of Medicine in years 1988-1993. We recorded and
      analysed 1100 words with identical acoustic test. The research was conucted in 3
      4 days, 3 moths, 6 months and 1 year after operation in a non-echo chamber with
      special equipment in the Department of Mechanic and Vibro-Acoustic of the Academy
      of Mining and Metallurgy in Krakow, Poland. On the basis of obtain results, we
      found that recovery of voice, in one year after surgery, occurs in 87.5% patients
      with laryngeal recurrent nerve injury.

PMID- 11339018
TI  - [Distribution of dopamine D1 receptors in the paraventricular nucleus of the rat
      hypothalamus and their colocalization with phosphorylated forms of CREB protein].
AB  - The aim of the present immunohistochemical study was to investigate distribution
      of dopamine D1 receptors in the paraventricular nucleus of hypothalamus and to
      estimate whether D1 receptors colocalize with pCREB protein, a functional marker
      of stimulation generated via receptors positively linked to cAMP/PKA system. D1
      receptors were found in numerous neurones of the paraventricular nucleus of
      hypothalamus, especially in its magnocellular part. In double-staining
      experiment, 74% of all stained neurones showed colocalization of D1 receptors and
      pCREB protein, 23% of neurones was pCREB-positive only and 3%--D1 receptor
      positive only. The presence of D1 receptors in the paraventricular nucleus of
      hypothalamus indicates that these receptors may be possibly engaged in regulation
      of the endocrine system (release of oxytocin, vasopressin or CRH). Almost
      complete colocalization of D1 receptors with pCREB protein suggests that these
      receptors are likely functional (active). The presence of D1 receptors and pCREB
      protein in studied structures of rat brain, as well as the specificity of applied
      antibodies were confirmed by Western Blot method. It was demonstrated that
      antibodies against D1 receptor and pCREB protein recognized main bands with
      molecular weight approximately 40 and approximately 46 kDa, respectively, what
      correlates well with the literature data.

PMID- 11339019
TI  - [The role of the autonomic nervous system on malfunction of gastric motor and
      myoelectric activity in patients with hyperthyroidism].
AB  - The aim of this study was to determine both the type of gastric mioelectric and
      emptying disorders in correlation to degree of severity of hyperthyroidism
      (clinical and thyroid hormones' blood levels) and ANS function estimated in HRV
      analysis. The study was performed on a group of 50 patients (35 with multinodular
      toxic goitre and 15 with Graves' disease, 45 females and 5 males, mean age 39.6
      years, mean BMI 23.72) with newly diagnosed and so far untreated hyperthyroidism.
      The control group were 50 healthy volunteers age-, sex-, and BMI-matched to the
      studied group. Patients were studied twice, within newly diagnosed
      thyreotoxicosis and after treatment (Metizol) and reaching stable euthyroid
      state. The study consisted of: a) percutaneous EGG analysis (Synectics): 30
      minutes before and after a test meal (ENRICH Liquid 250 ml), b) HRV analysis (ECG
      POSTER 2002): 10 minutes at rest and during deep breathing test, c) ultrasound
      measurement of gastric emptying by Bolondi method. Statistical analysis of
      collected data was performed. In hyperthyroid patients significant both
      preprandial and postprandial dysrhythmia (33.01% of bradygastria and 16.49% of
      tachygastria) was found. In some patients decrease of amplitude of EGG signal was
      marked as a result of antral hypomotility with coexisting significantly prolonged
      gastric emptying (110 min). Among severe hyperthyroid patients both the antral
      food distribution (antrum 35% bigger than in a control group) and impaired
      proximal stomach relaxation were evident. The degree of gastric mioelectric
      activity and emptying disorders was proportional to the degree of both severity
      of clinical manifestation of hyperthyroidism in Zgliczynski scale (from I degree
      to III degrees) and free thyroid hormones' blood levels (positive correlation).
      In HRV analysis at rest in hyperthyroid patients comparing to a control group the
      decrease of both the heart rate variability and a total power was found
      particularly in HF component resulting in relative sympathetic activation. In HRV
      analysis during deep breathing test the decrease of heart rate variability was
      present mostly in LF component. It indicates on reduction of vagal regulation
      (and vagal excitability) of sinus node and gastric pacemaker function.
      Coexistence of the increase and decrease of a gastric basic electrical rhythm
      with delay of gastric emptying indicates on a complex mechanism of their
      formation. Both neurogenic regulation dysfunction and primary miogenic
      autoregulation disorders as a result of tyreotoxicosis seem to be the possible
      causes. All the found changes were functional and disappeared after reaching the
      stable euthyroid state within 3 months of pharmacological treatment.

PMID- 11339020
TI  - Stats & facts. What is the status of the physician-hospital organization?

PMID- 11339021
TI  - Disruptive innovations threaten revenues and profits.

PMID- 11339022
TI  - Federal regulations, patient privacy, and the implications for managed care
      pharmacy.

PMID- 11339023
TI  - Economic evaluation of major selective serotonin-reuptake inhibitors in a managed
      care population.
AB  - This study evaluated pharmaceutical charges and economic outcomes related to
      therapy with the three leading selective serotonin-reuptake inhibitors. Patient
      treatment episodes of major depression occurring between July 1, 1995 and June
      30, 1996 were included for analysis (patient age range, 18-64 yr). Results showed
      no significant differences among direct and related medical charges for
      fluoxetine, paroxetine, and sertraline. Direct and related pharmaceutical charges
      were significantly lower for paroxetine and sertraline compared with fluoxetine.
      The higher drug charges observed for fluoxetine resulted in higher total
      treatment charges compared with paroxetine and sertraline.

PMID- 11339024
TI  - Antibiotic resistance: practice guidelines and attitude changes.

PMID- 11339025
TI  - Evidence-based guidelines for treatment of bacterial respiratory tract infections
      in the era of antibiotic resistance.
AB  - Antimicrobial resistance in bacterial respiratory tract pathogens is a rapidly
      evolving and increasingly disconcerting problem. Major factors that have
      contributed to resistance are inappropriate prescribing of antibiotics for viral
      infections and the use of antibiotics with poor activity. The treatment of
      respiratory tract infections is significantly affected by resistance in organisms
      such as Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella
      catarrhalis. Resistance to beta-lactams, sulfonamides, and macrolides continues
      to rise. Evidence-based guidelines, founded on clinical and bacteriological
      outcomes, are imperative to treat patients effectively, to limit the spread of
      these pathogens, and to minimize further development of resistance.
      Pharmacokinetic and pharmacodynamic parameters have recently been shown to
      correlate with clinical outcome, and offer a more rational approach to predicting
      antimicrobial efficacy and determining clinically relevant susceptibility
      breakpoints.

PMID- 11339026
TI  - Information technology answers the call for quality health care.

PMID- 11339027
TI  - Disease Management Leadership Forum, held in Baltimore, November 12-15, 2000.

PMID- 11339028
TI  - [Improved technology of simultaneous penetrating keratoplasty and second
      implantation of posterior chamber intraocular lens in complete or extensive
      absence of the posterior lenticular capsule].
AB  - The authors describe in detail improved technology of simultaneous keratoplasty
      and second (re)implantation of posterior-chamber disc intraocular lens (IOL) into
      aphakic and artiphakic eyes (103 operations) in cases with complete or extensive
      absence of the posterior capsule of the lens. Disc Saturn and TIOL IOLs with
      circulating supporting elements 7.5 mm in diameter were placed into the posterior
      chamber using a safe supporting suture and then fixed to the posterior surface of
      the iris in 2-3 sites. In order to prevent the pupil blocking, basal iridectomies
      were made in 2-4 sectors; intraoperative bleeding from iridal vessels was
      arrested by tamponade of the anterior chamber with a hemostatic collagen sponge,
      and "atonic" mydriasis was removed surgically. A lower incidence of intra- and
      postoperative complications (injuries to corneal graft endothelium and
      hemorrhages), reliable fixation of IOL, and good functional results (increase of
      visual acuity by 0.05-0.8 diopters) attained in 70% patients recommend this
      single-stage operation for practical ophthalmology.

PMID- 11339029
TI  - [Effects of reconstructive operations on the development of systemic
      autosensitization in patients with anophthalmos].
AB  - The role of systemic autoimmune reactions to organ-specific antigens (DNA and
      collagen) was studied in patients with anophthalmia before and after
      interventions on the stump and conjunctival cavity making use of autotransplants
      and synthetic implants. A total of 220 analyses of the serum were performed in
      the main group and 50 in the control. Autosensitization was detected in 10
      (18.2%) patients. The data were processed using Statistica software. A series of
      previous reconstructive operations is a factor promoting the development of
      systemic autosensitization to collagen. A trend to an increase in the levels of
      antibodies to DNA and collagen was observed in the presence of cicatricial
      changes in adjacent tissues, foreign bodies, cartilaginous implants, and fistulas
      causing a latent fibrous reaction. The type of intervention (use of implants or
      autotransplants) does not affect the level of antibodies to DNA and collagen.

PMID- 11339030
TI  - [Topography and angioarchitectonics of the orbital portion of the optic nerve
      according to ultrasonic findings and data of three-dimensional optic analysis].
AB  - Super-sharp gray scale image, highly sensitive digital wide-band Doppler
      analysis, three-dimensional visualization of vessels in pulsed energy Doppler
      mode, and three-dimensional optic tomography of the optic disk were used in
      examination of the posterior segment of the eye in 20 healthy volunteers (40
      eyes) aged 20-50 years. Vascular network of the optic nerve was examined under
      clinical conditions; blood filling of elements of the Zinn-Haller arterial
      circle, reticular plate, and posterior short ciliary arteries were studied.
      Vascular architectonics of the retrobulbar space was studied by three-dimensional
      reconstruction in the energy Doppler mode and biometrical parameters of
      intraocular and retrobulbar part of the optic disk were determined.

PMID- 11339031
TI  - [Possibilities of spatial discriminative perimetry in the diagnosis of partial
      atrophy of the optic nerve].
AB  - A method for investigating spatial discriminative sensitivity at a site of 20
      degrees from the point of fixation is proposed for studies of changes in the
      ocular system at early stages of partial optic nerve atrophy. Normal values of
      distribution were determined on 20 volunteers. The main group consisted of 8
      patients with initial glaucoma. Manifest changes in spatial discriminative
      sensitivity, correlating with changes in the central visual field, were detected
      in all patients with glaucoma. This method represents a variant of analysis of
      the resolving capacity of optic analyzer, allowing detection of its early
      changes.

PMID- 11339032
TI  - [Blood flow in ocular vessels in 2 types of ocular ischemic syndrome].
AB  - Ultrasonic triplex scanning of the orbit (gray scale two-dimensional ultrasonic
      examination, color Doppler mapping (CDM), and dopplerography) was carried out in
      148 patients with ocular ischemic syndrome (OIS) aged 35-70 years, 104 of these
      with acute and 44 with primary chronic course. Signs of disordered bloodflow in
      the orbital and central retinal arteries were detected in patients with acute
      disease: 2-fold decreased maximum systolic bloodflow velocity, 5-fold decreased
      end diastolic bloodflow velocity, and 1.5 times increased resistance index in
      comparison with the norm. Chronic course of OIS was characterized by decreased
      maximum systolic velocity (by 1.5 times) and end diastolic bloodflow velocity (3
      fold) in comparison with the norm in both arteries. Studies of ocular bloodflow
      by CDM timely detected angiological disorders in OIS and help define (in
      cooperation with angiosurgeon) the indications for angioreconstructive
      operations.

PMID- 11339033
TI  - [Thrombocytopathies and their role in the development of hemorrhagic syndrome in
      vascular diseases of the fundus oculi].
AB  - Examinations of 407 patients with angiological disorders of the fundus oculi
      (diabetic retinopathy, retinal vein thrombosis, central chorioretinal dystrophy,
      retinal angiitis) revealed relapsing hemorrhagic syndrome in 40% (170) patients.
      No thrombocytopenia was revealed in any of the patients, which suggests
      qualitative impairment of platelets in such patients. Evaluation of the platelet
      aggregation coefficient (PAC) using thrombin aggregation inducers and adenosine
      diphosphate disodium revealed a statistically significant decrease of PAC for one
      or both aggregants in all 170 patients with the hemorrhagic syndrome, which
      indicated platelet dysfunction. A course of intramuscular injections of 1%
      adenosine triphosphate sodium normalized platelet function and stimulated
      resorption of hemorrhages.

PMID- 11339034
TI  - [Evaluation of mechanical and ultrasonic characteristics of the lens nucleus].
AB  - Acoustic examinations of the lens were carried out in patients with cataracts of
      different degree of maturing and mechanical solidity of the nucleus was measured
      after surgery. An original method of ultrasonic examination with Humphrey's A/B
      scanning system was used. Ultrasonic density was 10-15% increased in more mature
      forms of cataract, which was confirmed by postoperative measurements of the
      nucleus solidity by means of 2034 TMR microhardness meter (the solidity was
      increased by 15-20 mN). Correlation between the findings of ultrasonic scanning
      and mechanical solidity was direct and strong (p < 0.05). Therefore, the proposed
      ultrasonic method can be used in cataract surgery for evaluating the solidity of
      the lens nucleus before surgery.

PMID- 11339035
TI  - [High performance liquid chromatography identification of chloracetophenone in
      ocular tissues in burns induced by gas balloons (an experimental study)].
AB  - The kinetics of chloracetophenone (CN) in rabbit eyes was studied by high
      performance liquid chromatography on a model of experimental third-degree burn.
      By the end of the first hour after exposure to the lacrimate, CN content was high
      in all the studied tissues: 28.5 +/- 0.563 x 10(-1) mg/kg in the cornea, 5.08 +/-
      0.193 x 10(-1) mg/kg in the anterior chamber humor, and 3.26 +/- 0.123 x 10(-1)
      mg/kg in the vitreous. After 6 h the content of the irritant dropped almost
      threefold and was 8.5 +/- 0.403 x 10(-1) mg/kg in the cornea, 1.23 +/- 0.062 x
      10(-1) mg/kg in the anterior chamber humor, and 0.017 +/- 0.006 x 10(-1) mg/kg in
      the vitreous. By the end of 24 h these values were 6.6 +/- 0.221, 1.46 +/- 0.123,
      and 0.015 +/- 0.005 x 10(-1) mg/kg, respectively, and by day 14 only trace
      amounts of CN were detected. Hence, CN in the Cheremukha gas balloons can
      penetrate into the inner structures of the eye and cause severe injuries.
      Persistence of CN for up to 14 days disordered the metabolic processes and
      anatomy of the eye. High content of CN during the first 7 days after burn
      requires adequate pathogenetic therapy.

PMID- 11339036
TI  - [Effects of trans-scleral laser cyclo-coagulation on intraocular pressure and
      visual function in patients with far advanced open-angle glaucoma].
AB  - Transscleral diode laser cyclocoagulation was modified so that laser coagulants
      (20-25 applications) were applied not only to the ciliary crown, but to the flat
      part of the ciliary body as well. Inflammation modulators forming after
      coagulation thus enter aqueous humor and the vitreous body and penetrate into the
      retina and optic disc, causing dilatation of capillaries and stimulating the
      blood stream in them. Forty patients (40 eyes) with far advanced glaucoma and
      pronounced concentrical narrowing of the visual field were operated on and
      observed for 6-12 months postoperation. One month after the intervention
      intraocular pressure decreased by 9-21 mm Hg and was below 22 mm Hg in 38 eyes;
      visual acuity increased by 0.1-0.3 in 11 cases; visual field widened in all
      patients. These results did not appreciably change till the end of the period of
      observation.

PMID- 11339037
TI  - [Clinical variants and immunologic features of rheumatoid uveitis in children of
      different age].
AB  - Variability of clinical manifestations of rheumatoid uveitis, possibility of an
      atypical course (peripheral or panuveitis), and greater severity and specific
      features of the disease in case of its early (before the age of 3 years)
      manifestation are demonstrated on the basis of observations of 79 patients with
      rheumatoid uveitis. Despite systemic therapy with corticosteroids and
      cytostatics, no manifest post-steroid immunodeficiency was observed. Moderately
      expressed gammapathies were detected in 60% cases; hypoimmune states
      predominated, which were more often detected in children aged under 6 years. No
      cases of pronounced suppression of functional activity of lymphocytes were
      observed. Humoral and cellular response to persistent ophthalmotropic infections
      were observed more rarely than in children with uveitis of other etiology.
      Positive rheumatoid factor was detected in 9% cases, antinuclear antibodies in
      60%. Antibodies to DNA were detected in the sera of 10% examinees, to native and
      denatured DNA in the lacrimal fluid of 21.2 and 16.7%, respectively. The causes
      of absence of obvious post-steroid immunodeficiency and relatively low rate of
      interorgan autosensitization in children with juvenile rheumatoid arthritis and
      uveitis are discussed. Further investigation of clinical and immunological
      correlations are needed for improving the prediction of the course of rheumatoid
      uveitis and development of treatment strategy.

PMID- 11339038
TI  - [Time course of interferon status of patients with herpetic keratitis during
      treatment with actipol, a new inteferon inducer].
AB  - Interferon (IFN) status was evaluated in 20 patients with various forms of
      herpetic keratitis over the course of treatment with actipol (0.07% para
      aminobenzoic acid). Actipol was injected subconjunctivally parabulbarly in
      combination with instillations into the conjunctival sac or only instilled,
      depending on the disease severity. The following parameters were evaluated: 1)
      total content of various IFN types in circulating blood and 2) leukocyte capacity
      to produce IFN in vitro in patient's whole blood cells. IFN-alpha was induced
      with Newcastle disease virus and IFN-beta with staphylococcal enterotoxin. Before
      treatment IFN-producing capacity of blood cells in vitro was decreased in 60%
      patients and was normal or increased in 40%. Plasma concentrations of IFN were
      moderately increased in 45% patients. All IFN parameters in patients with
      initially disordered IFN status normalized during actipol therapy and after
      clinical cure and did not change in the patients with initially normal IFN
      values. Hence, local actipol therapy in patients with various forms of ophthalmic
      herpes modifies IFN status.

PMID- 11339039
TI  - [Effects of specialized laser keratomileusis on the concentration of potassium
      ions in the lacrimal fluid].
AB  - The content of potassium ions in the lacrimal fluid was evaluated before and in
      various periods after laser specialized keratomileusis (LASIK) in order to
      determine the scope and terms of therapeutic measures. Seventeen patients with
      myopia were examined before and after LASIK. Lacrimal production before the
      operation was evaluated by Schirmer's and Norn's tests. The concentration of K+
      ions in the lacrimal fluid was measured on a Reflotron IV biochemical analyzer.
      Before operation the concentrations of potassium ions were 1.5 times higher than
      normally in the patients complaining of discomfort. Lacrimal concentration of K+
      ions and results of Norn's and Schirmer's tests were in high correlation. After
      LASIK potassium ion concentrations were increased in all patients and returned to
      the initial level almost completely within 1 week postoperation. Treatment with
      artificial tear preparations containing no potassium ions during the early
      postoperative period is physiological.

PMID- 11339040
TI  - [2-year follow-up of the use of a new fistulization operation in patients with
      refractory glaucoma].
AB  - A new full-thickness operation is described and its results in 45 patients (46
      eyes) with refractory glaucoma are analyzed. The patients were observed for 18.6
      months after the intervention. By the end of the first year postoperation
      intraocular pressure was compensated in 43 (93.5%) eyes, in 7 (15.2%) of these
      hypotensive therapy was needed. The operation is effective and safe for patients
      at a high risk of excessive cicatrization.

PMID- 11339041
TI  - [Relationship between clinical manifestations of acute and subacute attacks of
      closed-angle glaucoma and state of hemodynamics of the orbital artery basin].
AB  - Clinical and angiological studies were carried out in 50 patients (55 eyes) with
      open-angle glaucoma at the moment of clinical attack. Acute attacks were observed
      in 21 (38.18%) eyes and subacute (without strangulation and inflammation) in 32
      (61.82%) eyes. The findings indicate an important role of the hemodynamic status
      of the orbital artery in the development of strangulation and inflammation
      phases, as decreased level of hemodynamics in the iridal vessels facilitates
      their strangulation and initiation of the inflammatory phase of acute attack,
      which do not develop during a subacute attack of open-angle glaucoma. A subacute
      attack of closed-angle glaucoma is characterized by high values of hemodynamics
      in the orbital artery basin. This gives us grounds to regard an acute attack of
      glaucoma (strangulation and inflammation) as a decompensation phase between hemo-
      and hydrodynamic processes in the eye.

PMID- 11339042
TI  - [Bullous form of X-linked congenital retinoschisis in infants].
AB  - Clinical manifestations and course of bullous X-linked congenital retinoschisis
      were studied in 10 infants aged 6-18 months. Visual function was evaluated by
      registration of electroretinogram and visual evoked potentials. The patients were
      followed up for 7.65 +/- 2.51 years. Giant retinal cysts were observed in 40%
      patients with X-linked retinoschisis aged under 3 years. Collapse (spontaneous or
      after laser coagulation of the retina) of retinal cysts with formation of
      demarcation pigmented lines was observed in 85% children. Twenty percent patients
      developed hemophthalmia which was completely resorbed within 4-12 months. At the
      age of 6-12 years visual acuity was 0.36 +/- 0.23. The prognosis of the condition
      is favorable, and therefore surgical treatment or laser coagulation are not
      recommended in infants with bullous retinoschisis, on condition that no negative
      changes in the disease course are observed.

PMID- 11339043
TI  - [Retinal vasculitis in Behcet's disease].
AB  - Behcet's disease (BD) is a multisystemic disorder characterized by primary
      vasculitis of unknown etiology. We studied retinal vasculitis in 35 patients with
      ocular form of BD. All patients fulfilled the International Study Group criteria
      for BD. Mean age was 30.8 +/- 6.5 years (19-45 years, mean follow-up period 4.1
      +/- 1.29 years (3-10 years. The disease occurred 3.3 times more often in men than
      in women (p = 0.0003). Retinal vasculitis was diagnosed in 26 (74.3%) of 35
      patients with ocular form of BD. Retinal vascular changes characteristic of BD
      were bilateral in 96.1% cases and involved both arteries and veins. The earliest
      changes were detectable only by fluorescent angiography. Diffuse capillary
      leakage was observed in all cases during the active period of disease, involving
      the posterior pole. The disk and macular capillaries were involved most of all.
      Late staining of vasculature was observed in 68.6% patients. No ruptures of
      retinal vessels, retinal neovascularization, or areas of retinal nonperfusion
      were observed (except one case with occlusion of a branch of the central retinal
      vein), which are usually seen in other types of retinal vasculitis. Visual acuity
      was significantly decreased in patients with retinal occlusive vasculitis in
      comparison with patients without it (0.04 +/- 0.09 vs. 0.3 +/- 0.3, p = 0.029).

PMID- 11339044
TI  - [Clinical aspects of ocular tuberculosis of different localization].
AB  - Detailed study of a representative clinical sample and monitoring of 410 patients
      with ocular tuberculosis enabled the authors disclose the pathomorphosis and
      describe the clinical features of the disease. Tuberculosis of anterior location
      is observed at middle age and is characterized by frequent relapses, monolateral
      involvement, predominance of mixed and exudative inflammation, and high incidence
      of complications. Posterior tuberculous uveitis more often occurs in young people
      and is characterized by involvement of one or both eyes, productive inflammation,
      long remissions, and lesser incidence of complications.

PMID- 11339045
TI  - [Surgical rehabilitation of a patient with corneal perforation in
      keratoconjunctivitis sicca syndrome].
AB  - The authors describe effective surgical rehabilitation of a female patient with
      corneal perforation and subsequent complicated cataract developing against the
      background of chronic deficiency of lacrimal production associated with Sjogren's
      syndrome which developed in the presence of rheumatoid arthritis. Treatment with
      artificial tears during complex pre- and postoperative therapy prevented serious
      complications and made unnecessary the preliminary interventions aimed at
      inhibition of lacrimal production. Long remission of the underlying disease and
      stability of visual functions during 2 years evidence the efficiency of
      rehabilitative measures.

PMID- 11339046
TI  - [Intranasal electrophoresis].

PMID- 11339047
TI  - [Pathogenetic principles of the therapy of retinal ischemia in vascular diseases
      of the fundus oculi based on studies of the role of nitrogen oxide].

PMID- 11339048
TI  - [Improvement of ophthalmological services in the Bashkortostan Republic].

PMID- 11339049
TI  - [Comparative evaluation of the tolerability of proxofelin and clofelin and their
      effects on the eye in patients with glaucoma].
AB  - Tolerance and effects of proxofelin (1% proxodolole and 0.25% clofelin) and
      clofelin were compared in 39 patients (50 eyes) with primary open-angle glaucoma
      by open and double-blind methods. Intraocular pressure, ocular hydrodynamics,
      arterial pressure, and heart rate were examined before and on day 28 of
      treatment. The hypotensive effect of proxofelin was more expressed than that of
      clofelin, the drugs decreasing intraocular pressure by 37 and 27% of the initial
      value, respectively. Proxofelin decreased ophthalmic tone, significantly
      increasing the coefficient of fluid discharge easiness by 50% and decreasing the
      production of aqueous humor by 51.9%, while clofelin slightly (14%) increased the
      coefficient of fluid discharge easiness and decreased intraocular pressure mainly
      at the expense of suppressing aqueous humor secretion. Hence, the combined drug
      is preferable in comparison with the monopreparation. Moreover, proxofelin was
      well tolerated by the patients, which differs it favorably from clofelin.

PMID- 11339050
TI  - [A new operation in the treatment of refractory glaucoma: limbo-sclerectomy with
      valvular drainage of supraciliary space].
AB  - A new antiglaucoma operation has been developed: limbosclerectomy with valvular
      drainage of the supraciliary space. The operation was performed on 82 eyes with
      artiphakia, pseudophakia, and previously operated primary open-angle glaucoma.
      The patients were observed for 1.3 +/- 0.6 years after the intervention.
      Compensation of intraocular pressure and a significant increase in the
      coefficient of liquid discharge facility were observed in remote periods in all
      patients: in 95.1% patients without hypotensive therapy and in 4.9% cases
      instillations of 0.5% thimolol maleate twice a day were needed. Visual acuity and
      visual field borders did not appreciably change after the intervention. The
      operation is recommended for practice.

PMID- 11339051
TI  - [Airborne molds in Nantes--effect of climatic factors].
AB  - Many cities are studying biological atmospheric and, particularly, pollen
      pollution, but they are having difficulties setting up a mold analysis network
      and only a few provide fungal spore counts. The significance of some of those
      spores, and Alternaria in particular, as major allergens is now well known. The
      number of Alternaria spores varies extensively according to weather conditions
      over the year.

PMID- 11339052
TI  - [Mold allergy: 25 years of indoor and outdoor studies in Belgium].
AB  - Collecting atmospheric fungal spores in Brussels for 25 years revealed
      significant quantitative differences at three different levels: the total number
      of spores collected every year, the annual frequency rate of some species e.g.
      Cladosporium and Alternaria, the proliferation of some rare species according to
      weather conditions.

PMID- 11339053
TI  - [Physiopathology of hay fever].
AB  - Pollinosis is a model physio-pathology for IgE-dependent diseases. Rhinitis and
      conjunctivitis are the parent symptoms, with asthma a non-exceptional
      complication. The mechanisms are linked to an immuno-allergic inflammation; the
      observed differences are due to specific anatomo-physiologies of the sensitive
      cells. The pollen allergens are collected by the CPA and expressed after cleavage
      into peptides, at the surface of the CPA in association with class II HLA
      molecules. T-lymphocytes recognise the complex HLA-peptide molecules. Type Th2
      lymphocytes produce the cytokines that the necessary for the synthesis of IgE
      (IL4, IL13...). At the stage of silent clinical sensitivity the precocious and
      delayed effector stages of immediate hypersensitivity follow. The precocious
      stage corresponds with degranulation of cells that express Fc epsilon R1, for
      release of vaso-active and lipid mediators that produce the immediate symptoms of
      pollinosis. The delayed phase corresponds with a flood of eosinophils, which
      release their toxic proteins proteins and also take part in oedema and nasal
      obstruction. Mucosal innervation, neurotransmitters and neuromediators also
      intervene in the modulation of symptoms.

PMID- 11339054
TI  - [Deposition of particles in the respiratory tract].
AB  - In order to appraise the site of deposition of an aerosol of particles in the
      airways, it is important to analyse the size distribution of the particles that
      form the aerosol by granule size range analysis. The three main different
      mechanisms involved in deposition of an aerosol are inertia impaction,
      sedimentation and brownian diffusion, and one or another predominates, according
      to the size of the inhaled aerosol. Finally, several factors may influence the
      deposition in the respiratory tract: anatomy of the airways, the respiratory
      method, the size range and the moisture content of the aerosol, smoking and
      respiratory pathology. Only by taking into account all these factors can an
      assessment be made of the deposition site in the airways of the inhaled
      particles.

PMID- 11339055
TI  - [Physiopathology of particle attack: animal and in vitro models].

PMID- 11339056
TI  - [Epidemiology of respiratory virus infections].
AB  - Respiratory viral infections are very common in young children. They sometimes
      occur as primary infections (and sometimes re-infections) by influenza and
      parainfluenza virus, respiratory syncytial virus (VRS), adenovirus, rhinovirus
      and coronavirus. The clinical pictures are very varied and without strict clinico
      virological correlation. In adults the role of the site (frail lung, aged
      persons) and the type of virus play an important part. Many viral infections
      develop in an epidemiological way (influenza, VRS bronchiolitis, rhinovirus
      infections...) and several epidemics by different viruses overlap from September
      October to March-April making it very difficult to decide the precise cause.
      Epidemics are followed thanks to networks of medical practitioners (GROG,
      SENTINELLE...) and by data from hospitalised patients, but precise identification
      of epidemic viruses is only possible and validated by virological analysis of
      samples taken from patients.

PMID- 11339057
TI  - [Epidemiology of the cardiorespiratory effects of particulates].
AB  - This review summarises the epidemiology of cardio-pulmonary effects of air
      pollution particles. The published studies that are reviewed here, were published
      between 1990 and 2000. First, the study designs, used in air pollution
      epidemiology, are defined. Second, the health effects of acute exposure are
      related, such as mortality, respiratory effects, effects on allergy and asthma
      and cardio-vascular effects. Third, the effects of chronic exposures are
      described, with also mortality, respiratory effects, effects on allergy and
      asthma, cardio-vascular effects, and effects on cancer incidence. Finally, the
      numerous studies published this last ten years, highlight a coherent cascade of
      cardio-pulmonary effects in relation to particles air pollution.

PMID- 11339058
TI  - [Virus and respiratory allergy in children].
AB  - Links between viruses and respiratory allergy are not easy to understand in
      children. For example, the risk of atopy or asthma is increased after an
      infection with syncytial respiratory virus. In some studies, more the child
      suffers from viral infections, more the risk of atopy increases. On the other
      hand, other studies state that the development of allergy is reduced if a child
      enters day nursery before 12 months, and consequently if he is exposed early in
      life to viruses. Measles and hepatitis A viruses could also protect from allergy.
      In fact, viruses seem modulate the expression of a preexisting atopic status.
      Depending on their nature and their circumstances of occurrence, they could
      induce some sensitizations or inversely protect from atopy by facilitating the
      lymphocyte Th2 or Th1 response.

PMID- 11339059
TI  - [Calls to the SAMU Centre 15 (Emergency Medical Service Center 15): an indicator
      of peak pollen concentrations].
AB  - A retrospective analysis of the calls received by the emergency services in
      Montlucon and the outpatient dossiers in the Adult and Pediatric Emergency
      Departments for June 3 to 5, 2000 evidenced an increase in the number of requests
      made for assistance regarding pollinosis symptoms. These symptoms and the
      associated requests for assistance seem to have been caused by Poaceae pollen
      peaks, ozone peaks and specific weather conditions. Hence, the number of calls
      received by the emergency services can be viewed as an unfavorable indicator for
      pollen-related diseases.

PMID- 11339060
TI  - [Cupressaceae hay fever].
AB  - Cypress allergy or rather Cupressaceae allergy is an extraordinary observation
      subject and study model. Annual R.N.S.A. meeting is a good opportunity to share
      the analysts and sentinel doctors' point of view on this subject. For the
      medicine sentinel of the Nimes's pollen site, the development of these
      Cupressaceae sensitivities is becoming a true public health priority. This
      feeling is shared by the southern sector responsible of the French network. It is
      absolutely necessary to develop actions.

PMID- 11339061
TI  - Microarray technology: the future of blood testing?
AB  - The increasing pace of development in molecular biological techniques during the
      last 10-15 years has had a direct effect on mass testing and diagnostic
      applications, including blood screening. Nucleic acid amplification techniques
      (NAT), usually based on the polymerase chain reaction (PCR), have been
      successfully applied to blood grouping and implemented recently in screening of
      blood donations for hepatitis C virus (HCV). The majority of microarray
      technologies involve an amplification step, yet the main benefits of this
      technology come from simultaneous analysis of thousands of analytes. Microarrays
      were developed to utilize the huge amount of information provided by genome
      projects, but they have clear potential in mass screening and diagnostics. The
      application of microarray technology may revolutionize blood testing, providing
      for the first time the prospect of an integrated platform for comprehensive donor
      and donation testing, replacing multiple individual assays. Design features of a
      blood-testing chip and various technologies with potential application in this
      field are discussed in this review.

PMID- 11339062
TI  - DNA vaccination: a potential weapon against infection and cancer.
AB  - DNA vaccination is a novel approach for inducing immunity against target
      antigens. It provides a direct link between identification of genes encoding
      these antigens and incorporation of the gene sequences into a vaccine vehicle.
      Identification of candidate genes is proceeding very rapidly both for infectious
      organisms and for cancer cells. One advantage is that DNA appears to activate all
      pathways of immunity, especially cytotoxic T-cell responses, which have been
      difficult to induce with protein vaccines. For viruses, including those which
      have caused problems for blood transfusion, DNA vaccination could be used for
      prevention. However, for chronic infection, or for cancer, vaccination will be
      performed in a therapeutic setting. For this situation, it is probable that
      immune-activating sequences will have to be included in the vaccine. The ease of
      manipulation of gene sequences, together with the increasing knowledge of the
      operation of the immune system, means that we now have the tools to take vaccines
      into the next exciting stage of development.

PMID- 11339063
TI  - Efficacy of a hepatitis C virus core antigen enzyme-linked immunosorbent assay
      for the identification of 'window-phase' blood donations.
AB  - BACKGROUND AND OBJECTIVES: Recent studies have suggested that potentially
      infectious donations provided during the antibody-negative 'window' phase of
      hepatitis C virus (HCV) infection may be identified by testing for viral RNA or
      HCV core protein. We therefore evaluated the performance of an HCV antigen enzyme
      linked immunosorbent assay (ELISA) for identification of window-phase donations
      and for prospective screening of blood donors. MATERIALS AND METHODS: One-hundred
      and twenty-eight archived plasma donations containing HCV RNA, but lacking
      antibody to HCV (anti-HCV), were tested by using the HCV antigen ELISA, together
      with 9951 freshly collected serum and plasma specimens from blood donors.
      RESULTS: HCV core antigen was detected in 94% (120/128) of window-phase plasma
      donations. Overall specificity in freshly collected blood donor specimens was
      99.74%. Two putative window-phase donations containing HCV core protein and viral
      RNA were identified from paid plasma donors by prospective testing with the HCV
      antigen ELISA. CONCLUSION: These results indicate that an HCV antigen ELISA can
      identify almost all (94%) of viraemic donations given during the seronegative
      window phase of infection. The performance of the HCV antigen ELISA appears to be
      suitable for large-scale screening of blood donations.

PMID- 11339064
TI  - Risk behaviour among blood donors who give blood in order to be tested for the
      human immunodeficiency virus.
AB  - BACKGROUND AND OBJECTIVES: There has been concern that some individuals may
      donate blood primarily motivated by the easy access to human immunodeficiency
      virus (HIV) testing, and that such donors may represent a risk to the transfusion
      service. In this article we focus on the risk behaviour of donors who reported
      that they gave blood in order to be HIV tested. MATERIALS AND METHODS: Anonymous
      questionnaires were given to 5859 blood donors. The response rate was 70%.
      RESULTS: Of the responders, 2.8% reported to have donated blood in order to be
      HIV tested. However, 87% of the donation-for-test group did not have any
      identified risk behaviour. CONCLUSIONS: The proportion who donated blood in order
      to be HIV tested was higher than expected, but the majority of the group did not
      have any identifiable HIV risk.

PMID- 11339065
TI  - Validity of the haemoglobin colour scale in blood donor screening.
AB  - BACKGROUND AND OBJECTIVES: The haemoglobin colour scale (HCS) has been developed
      as a simple, reliable and inexpensive clinical device for diagnosing anaemia and
      estimating its severity when laboratory-based haemoglobinometry is not available.
      The purpose of this study was to assess its validity for screening blood donors
      for anaemia. MATERIAL AND METHODS: The HCS was tested at five blood transfusion
      centres on a total of 2801 donors. Blood was obtained by skin puncture as part of
      the routine procedure at the donor sessions. HCS readings were compared with
      screening by the copper sulphate method, which was in routine use in the centres,
      and with haemoglobin (Hb) measurements by means of calibrated HemoCue
      haemoglobinometers. HCS readings were considered as normal when the readings were
      > or = 12 g/dl. RESULTS: Analysis of the paired results showed that the HCS had
      an accuracy of 97.5% in distinguishing subjects with normal Hb from those below
      the acceptable limit, when checked against the HemoCue. The HCS was more reliable
      than the copper-sulphate specific-gravity method, yielding 3.7% false readings
      compared with 6.1% false readings, respectively. When discrimination was set at
      12 g/dl with the HemoCue, the HCS gave an incorrect reading in 2.4% of donors.
      The majority of these false results (44 donors; 1.58%) were caused by the HCS
      indicating rejection of the donor (i.e. Hb < 12 g/dl) when the correct Hb was
      higher, whilst in 23 donors (0.82%) the HCS incorrectly indicated a normal Hb;
      however, in all but four of these donors the correct Hb values were 11.0-11.9
      g/dl, and none were below 10 g/dl. CONCLUSION: The operators were able to master
      the HCS technique after a few minutes of practice, and all found the test to be
      user friendly and easy to read. The HCS is proposed as a replacement for the
      copper sulphate method for blood transfusion donor selection.

PMID- 11339066
TI  - Automated blood-mixing devices still fail to mix at low bleeding rates.
AB  - BACKGROUND AND OBJECTIVES: The study evaluated mixing performance for various
      commercial blood-mixing devices at different flow rates. MATERIALS AND METHODS: A
      glycerol solution with a density equal to blood was pumped into a blood bag
      (mounted on a mixer) that contained 70 ml of Toluidin Blue in citrate-phosphate
      dextrose (CPD). After 500 ml of glycerol solution had been pumped into the blood
      bag, the bag was emptied in fractions and the absorbance at 640 nm of each
      fraction (expressed as percentage of mixture absorbance) was plotted against the
      fraction number. RESULTS: At a flow rate of 30 ml/min, the curves were very
      sigmoid, with high initial values that decreased during collection of the
      fractions. The absorbance values of the fractions collected later (after
      approximately 250-300 ml) were 10-50% (i.e. percentage of absorbance for complete
      mixing) for the different mixers, indicating that the CPD solution was
      incompletely mixed with the incoming solution, resulting in a lower-than-expected
      'anticoagulant' content for the fractions collected later. At a flow rate of 50
      ml/min the mixing was improved, but only at 75 ml/min did all mixers show
      relatively good mixing. Manual mixing, by kneading the bag three times/min, gave
      at all rates an almost ideal mixing curve, 105% initially to 90% in the final
      fractions. CONCLUSION: At relatively high bleeding rates, all mixers performed
      well, although complete mixing was only obtained with manual kneading. However,
      most blood-mixing devices still fail to mix efficiently at normal and low
      bleeding rates. Although the minimal degree of necessary mixing is unknown,
      further optimization of mixing devices seems warranted.

PMID- 11339067
TI  - Monitoring transfusion practices at two university hospitals.
AB  - BACKGROUND AND OBJECTIVES: Considering the clinical importance of blood
      transfusions, the limited knowledge of transfusion practices is remarkable. New
      methods are needed to elucidate the observed variation of transfusion practices.
      MATERIALS AND METHODS: All patients transfused or pretransfusion tested (i.e. at
      risk for blood transfusion) at two tertiary teaching hospitals during the full
      years of 1997 and 1998 were included in the study. RESULTS: The observed
      practices contained substantial variance at the level of hospitals. The
      contributions to the total variance of the different specialities were highly
      significant, as was the contribution of hospitals to the variance in plasma and
      platelet transfusions. Significant interactions between hospitals and
      specialities were observed in transfusion of red cells, plasma and platelets.
      CONCLUSION: To our knowledge this is the first survey of this size to combine
      transfusions, diagnoses and biochemical tests, exclusively based on an existing
      computerized register. The aim is to establish a basis for comparison of local
      transfusion practices with other commensurate hospitals and regions at a national
      (and international) level.

PMID- 11339068
TI  - 24-hour 51Cr post-transfusion survival, 51Cr life span and haemolysis of red
      blood cells stored at 4 degrees C for 56 days in AS-3.
AB  - BACKGROUND AND OBJECTIVES: Red blood cells (RBC) were collected either by a
      manual method using a 16-gauge needle or by an apheresis procedure using an 18
      gauge needle, and were stored at 4 degrees C in a solution of CP2D
      (anticoagulant)/AS-3 (Nutricel) for 56 days. The purpose was to compare the
      outcome of the autotransfused red cells collected by both techniques. MATERIALS
      AND METHODS: Five healthy male volunteers were studied on two occasions. RESULTS:
      The autotransfusions of the manual and apheresed RBC resulted in a mean 24-h post
      transfusion survival of 71%, a normal mean 51Cr RBC life span, a 2,3 DPG level
      that was less than 10% of normal, and 0.6% haemolysis. CONCLUSIONS: Whether
      collected manually or by apheresis, the outcomes were similar for RBC stored at 4
      degrees C for 56 days in CP2D/AS-3.

PMID- 11339069
TI  - Effect of leucocyte reduction on the potential alloimmunogenicity of leucocytes
      in fresh-frozen plasma products.
AB  - BACKGROUND AND OBJECTIVES: Adverse effects mediated by leucocytes in cellular
      blood products are widely recognized. There are few studies, however, concerning
      the effects of residual leucocytes in fresh-frozen plasma (FFP). We examined the
      quantities and characteristics of leucocytes in FFP in order to investigate the
      potential leucocyte-associated adverse effects of FFP transfusion, focusing on
      the risk of alloimmunization. MATERIALS AND METHODS: The quantity of leucocytes
      in FFP was estimated by using the Nageotte method and flow cytometry (FCM)
      analysis. The viability and subsets of leucocytes were determined by FCM using
      propidium iodide (PI) and fluorescein-conjugated antibodies. To investigate
      alloimmunogenicity caused by the leucocytes in FFP, mixed lymphocyte cultures
      (MLC) were performed using fresh, allogeneic peripheral blood mononuclear cells
      (PBMCs) as responder cells and cell-concentrated thawed FFP as a stimulator. We
      also studied the performance of leucocyte-reduction filters with FFP products.
      RESULTS: The average number of leucocytes in a single unit of FFP, derived from
      200 ml of whole blood, was 2.98 x 10(6) (range 0.99-8.38 x 10(6)). The majority
      of these cells were PI-positive dead cells; however, a small but consistent
      population of PI-negative cells was present in these products. Both dead and live
      cells expressed human leucocyte antigen (HLA) class I antigens, and approximately
      38% of these cells expressed HLA class II antigens. The average number of viable
      CD3+ T cells in one unit of FFP was 2.36 x 10(4). Growth of the allogeneic PBMCs
      increased following stimulation with highly concentrated FFP. Use of leucocyte
      reduction filters significantly reduced the concentrations of both PI-positive
      (dead) and PI-negative (live) cells. The growth of allogeneic lymphocytes after
      stimulation with FFP was also completely suppressed by leucocyte filtration of
      FFP. CONCLUSION: Transfusion of FFP is potentially alloimmunogenic owing to its
      residual leucocyte content. Leucocyte-reduction filters appear to be effective in
      suppressing the alloimmunogenicity of FFP.

PMID- 11339070
TI  - The 'cherry buffy-coat syndrome', a cause of decreased platelet yield in platelet
      concentrates obtained from buffy-coats.
AB  - BACKGROUND AND OBJECTIVES: A large number of European blood centres, including
      our own, use the buffy-coat method for platelet production. In this article we
      describe a previously unnoticed phenomenon shown by a proportion of buffy-coats,
      which display an unusually bright cherry colour and low platelet counts.
      MATERIALS AND METHODS: We performed bacterial cultures, platelet counts, pO2,
      pCO2 and pH, and evaluated platelet activation by flow cytometry in cherry versus
      normal-colour (control) buffy-coats. In addition, we compared donor
      characteristics in the two groups and platelet counts in the packed red blood
      cells (RBC) obtained from the original donations. Finally, we monitored the
      frequency of cherry buffy-coats in the bags of three manufacturers, and
      determined the concordance rate of two trained technicians in detecting cherry
      buffy-coats. RESULTS: Bacterial cultures were negative. Cherry buffy-coats
      contained significantly fewer platelets, more O2, less CO2 and had a
      significantly higher pH than normal buffy coats. Platelet activation was slightly
      higher in cherry buffy-coats. RBC from donations yielding cherry buffy-coats
      contained a significantly higher number of platelets than controls. Donor
      characteristics were not significantly different. Cherry buffy-coats were
      significantly more frequent with bags from one manufacturer (24%) than from
      others (9% and 11.6%). The concordance study showed excellent agreement.
      CONCLUSIONS: Our hypothesis is that the cherry colour is caused by O2
      accumulation in buffy-coats with low platelet counts. The latter may be caused by
      platelet activation and aggregation during blood processing. Further work is
      needed to determine the cause of this phenomenon, its frequency in different
      laboratories and means to prevent it.

PMID- 11339071
TI  - Is oral tolerance therapy possible for haemophilia with inhibitors?

PMID- 11339072
TI  - An international collaborative study to establish a World Health Organization
      international standard for hepatitis B virus DNA nucleic acid amplification
      techniques.
AB  - BACKGROUND AND OBJECTIVES: Twenty-two laboratories from nine countries
      participated in an international collaborative study to establish a World Health
      Organization (WHO) international standard for hepatitis B virus (HBV) DNA nucleic
      acid amplification techniques (NAT). MATERIALS AND METHODS: Three samples, AA, BB
      (both of which were lyophilized) and CC (which was a liquid preparation), were
      analysed using several different NAT assays. The mean HBV DNA content of each
      sample was determined from the study. RESULTS: Despite the range of assays
      (commercial and in-house) used by participants, there was good agreement among
      the overall mean 'equivalents'/ml obtained by the different assays, except for
      one laboratory (laboratory 4). The variation in estimates of log10
      'equivalents'/ml was 1.75-1.25 for the three samples if results from laboratory 4
      were excluded. The mean log10 'equivalents'/ml for all laboratories were 6.42 for
      sample AA, 6.30 for sample BB and 5.03 for sample CC (exclusion of results from
      laboratory 4 made little difference). The difference in titres between the two
      lyophilized samples (AA and BB) was not statistically significant but the titre
      of the frozen sample (CC) was significantly lower. Material AA (code 97/746) was
      accepted as the first WHO international standard for HBV DNA NAT assays and
      assigned a potency of 10(6) international units (IU)/ml. CONCLUSIONS: The titres
      (genome equivalents/ml) of three HBV preparations were determined by several
      laboratories using different NAT assays. This study enabled the establishment of
      an international standard, 97/746, for HBV DNA NAT assays.

PMID- 11339074
TI  - Using shadowed data.

PMID- 11339073
TI  - Report on the Tenth International Platelet Genotyping and Serology Workshop on
      behalf of the International Society of Blood Transfusion.
AB  - BACKGROUND AND OBJECTIVES: The aims of the 10th International Platelet Serology
      and Genotyping Workshop were to evaluate the proficiency of platelet immunology
      determinations. MATERIALS AND METHODS: There were 40 participants from 25
      countries of four continents. Thirty-eight institutions reported results for
      genotyping, and 38 institutions reported their serological results. For
      genotyping, EDTA-anticoagulated whole-blood samples were provided (to allow the
      inclusion of DNA-separation methodology in the analysis) as well as separated DNA
      of a and b alleles for human platelet antigen (HPA)-1 to -6. For serological
      evaluations, sera contained allo- and autoantibodies, and for sensitivity testing
      a standard freeze-dried sample of HPA-5 antibody. RESULTS: All participants
      reported HPA-1, -2, -3 and -5 genotyping results; HPA-4 was determined in 29
      laboratories and HPA-6 in 21. Results from 16 laboratories were concordant with
      the majority vote for all allotypes, eight institutions reported one deviation,
      five laboratories two, and nine laboratories three or more deviations. Twelve
      institutions had no deviation from the majority vote for HPA antibodies, nine had
      one, three had two, and 14 had three or more deviations. Most laboratories
      reported a reactivity of the standard anti-HPA-5b sample with HPA-5b platelets at
      a dilution of 1:4-1:8. Four laboratories detected anti-Gova in one sample.
      Seventeen laboratories reported no deviation from the majority vote for pan
      reactive platelet antibodies, 12 had one deviation, two had two, and seven had
      three or more deviations. In addition, seven participants reported antibodies
      against glycoprotein IV (GPIV), three against glycoprotein V (GPV) and three
      against CD 109. These results were discussed at a meeting organized jointly with
      the International Society of Blood Transfusion (ISBT) 2000 Congress. CONCLUSION:
      The results for pan-reactive antibodies were heterogeneous with most
      discrepancies from the majority vote. The provision of sufficient samples for
      many participants is difficult. Based on the results and discussion it is clear
      that frequent workshops are needed in the future. Therefore, workshops shall be
      organized regionally, and each region shall participate with one institution in
      international workshops. The latter are needed to assure international exchange
      of experience and quality.

PMID- 11339075
TI  - Jake's story: a middle-aged, working-class man's physical and spiritual journey
      toward death.
AB  - In this article, the author explores a middle-aged, working-class man's, Jake's,
      reaction to his life-threatening illnesses and to his impending death. The
      experiences of illness and dying demand the "thick description" of narrative.
      Just as the medical model of illness breaks down the person into symptoms and
      parts, the relational model of illness and death in narrative "puts him back
      together again" by embedding him in a personal and social history. This article
      finds that the experience of illness and dying are rooted in the tacit ethos of
      an individual's family and society. The cultural paradigms of gender and class,
      religious tradition, and the reaction of others to the dying person shape the
      individual's response to his approaching death.

PMID- 11339076
TI  - The meaning of skilled care providers' relationships with stroke and aphasia
      patients.
AB  - Little is known about the reciprocal influence of communication difficulties on
      the care relationship. To illuminate care providers' lived experiences of
      relationships with stroke and aphasia patients, narrative interviews were
      conducted with providers particularly successful at communicating with patients.
      A phenomenological hermeneutic analysis of the narratives revealed three themes:
      Calling forth responsibility through fragility, restoring the patient's dignity,
      and being in a state of understanding. The analysis disclosed caring with regard
      to the patient's desire, which has its starting point in intersubjective
      relationship and interplay, in which nonverbal communication is essential--that
      is, open participation while meeting the patient as a presence. Thus, care
      providers prepare for deep fellowship, or communion, by being available. They
      described an equality with patients, interpreted as fraternity and reciprocity,
      that is a necessary element in presence as communion. The works of Marcel, Hegel,
      Stern, and Ricoeur provided the theoretical framework for the interpretation.

PMID- 11339077
TI  - Death stories: acute exacerbations of chronic obstructive pulmonary disease.
AB  - The underlying premise of narrative research within social science literature is
      the belief that individuals most effectively make sense of their world by
      (re)constructing stories. Chronic Obstructive Pulmonary Disease (COPD) is a
      progressive degenerative respiratory disorder that affects approximately 15% of
      Canadians annually. Prior to the study discussed in this article, no research had
      been done to understand the frightening event of an acute exacerbation episode of
      COPD from the perspective of patients and their family caregivers. Hence, 10
      family-nurse units were interviewed during an acute exacerbation event. The
      participants told a number of near-death and shadow-of-death stories that
      describe these episodes as life changing and illustrate the centrality of these
      events in the participants' understanding of their chronic illness.

PMID- 11339078
TI  - Caring and expressions of spirituality by urban caregivers of people with stroke
      in African American families.
AB  - Expressions of spirituality by urban caregivers in African American families are
      the focus of the study discussed in this article. Data presented here were
      collected as part of a larger study that examined these caregivers' experience
      and meaning of caring as they influenced their capacity to care for people with
      stroke within their family systems. This study was executed within and supported
      the framework of systemic organization by Friedemann, according to which families
      as open systems strive for well-being. Spirituality, a component of well-being,
      is based on values concerning commitment, love, and affection. Eight themes
      concerning spirituality for all caregivers emerged from the data. Through
      spirituality, the caregivers felt well-being and were connected and comforted in
      difficult times related to caring.

PMID- 11339079
TI  - Can we research suffering?
AB  - Illness troubles us because it is an occasion of suffering, but research on
      illness has difficulty conceptualizing suffering--and naturally so because
      suffering is not a concept but a lived reality that resists articulation. Based
      on the work of Dorothy Smith, the author argues that the rhetoric of social
      science inadvertently increases suffering because it attempts to organize local
      experience within extralocal categories. He concludes with suggestions for
      changing research practices.

PMID- 11339080
TI  - Gender roles and/or styles in crisis: an integrative analysis of the experiences
      of fathers of children with cancer.
AB  - Despite a proliferation of research with families of children with cancer and
      gender differences in parental coping, few studies have explicitly explored the
      experiences of fathers of children with cancer. Using several different data
      collection efforts, including semistructured in-depth interviews and open
      workshops, this integrative analysis views fathers' experiences through the lens
      of gender. Findings suggest that fathers' experiences can be understood as
      influenced by gender identities, gender roles, and the gendered organization of
      support systems, employment, and health care institutions. The results suggest
      the need for interventions that provide fathers and entire families with the
      opportunity to develop new skills and coping strategies for dealing with the
      stresses and challenges of childhood cancer.

PMID- 11339081
TI  - Understanding and supporting African Americans' perspectives of end-of-life care
      planning and decision making.
AB  - Ethnicity has been found to explain some differences across ethnic groups
      regarding end-of-life care choices. African Americans appear to be less likely to
      know about advance directives and to complete them. Five community-based focus
      groups, consisting of 27 African Americans, were convened to explore their
      perspectives of end-of-life care planning and decision making. Content analysis
      revealed six themes: death is not an option, religiosity and end-of-life care
      planning is a paradox, the health care system is a microcosm of societal and
      historical events, a "trusted" family member or friend is the contract for life
      and-death options, ethnically relevant initiatives are essential to increase
      advance directives participation, and people are people. These themes serve to
      guide health care professionals in minimizing actions that increase African
      Americans' mistrust of the health care system not only in end-of-life situations
      but also in all of health care-related interactions.

PMID- 11339082
TI  - Taciturn patients in health counseling at a hospital: passive recipients or
      active participators?
AB  - This study explored patients' taciturnity as observed on videotape during
      hospital health counseling situations with a nurse. Health counseling sessions,
      38 in number, were videotaped, transcribed verbatim, and analyzed by using an
      adaptation of conversation analysis. The data analysis included information on 18
      selected patients who spoke little and did not introduce new topics, but rather
      supported the discussion on the theme chosen by the nurse. When we examined
      nurses' and patients' speech word by word, we discovered four participation
      frames that produced taciturnity: in the hands of professionals, compliant,
      guilty, and polite. These could fluctuate during interaction. The findings
      indicate that there is a need for a more extensive description of taciturn, or
      silent, patients. What has been interpreted as passivity in the literature can be
      interpreted more constructively. This insight can be useful for developing health
      counseling practice in hospitals.

PMID- 11339083
TI  - Ethical issues in the documentary data analysis of Internet posts and archives.
AB  - The documentary analysis of e-mail posts and archives for qualitative research
      has been outlined elsewhere. Although there is an increase in the number of
      studies being conducted on listserv and newsgroup material in health research,
      this has not always been accompanied by a careful, in-depth consideration of the
      concomitant ethical issues. Therefore, this article outlines the ethical
      considerations surrounding this form of research, including issues of accessing
      voices, consent, privacy, anonymity, interpretation, and ownership and authorship
      of research material.

PMID- 11339084
TI  - [Changes in cardiovascular risk factors after renal transplantation].
AB  - Authors examined the serum concentration of creatinine, uric acid, homocysteine,
      cystatine C, total cholesterol and triglyceride in 115 male and 77 female
      patients six months after the transplantation. The change of the BMI (Body Mass
      Index) was studied, fat and water body weight was determined by bioelectrical
      impedance analysis, and the ratio of intra- and extracellular volume was
      calculated. Both creatinine and cystatine C levels decreased significantly
      compared to the levels before the transplantation (p < 0.001) because of the good
      renal function, and there was a good correlation between creatinine, cystatine C
      and homocysteine levels (r = 0.5315 in females, r = 0.3189 in males). Elevated
      BMI (36.49%) and hypercholesterolaemia along with moderate hyperhomocysteinaemia
      was found in a considerable part of the patients. Increase in body weight was
      confirmed by the increase in fat body weight and volume determined by
      bioelectrical impedance analysis. In patients with adequate compliance the ratio
      of intra- and extracellular volume was between 1.67 and 1.79. Blood pressure
      values showed frequently the non-dipper phenomenon despite appropriate
      antihypertensive therapy, and negative diurnal index was found with high
      nocturnal blood pressure levels. The mean blood pressure was 148/81 +/- 13.2/4.8
      mmHg in males and 133/84 +/- 15.3/9.8 mmHg in females. Authors enhance the
      importance of regular monitoring of cardiovascular risk factors in the prevention
      of cardiovascular complications.

PMID- 11339085
TI  - [Evolution and change of strategy in carotid artery surgery in Debrecen].
AB  - In the 1st Department of Surgery, in Debrecen, operations on supraaortic arteries
      are done, since 1985. In the first five years, sporadically, only 2-3 carotid
      reconstruction have been done. Between 1990-1996 the number of these operations
      were about 20 per year, although the number of postoperative complications were
      around 1%. The number of operative interventions on the carotid region were
      doubled in 1997 and from 1999 were four times more. The authors analysed the data
      of the patients, accumulated in the last 6 years. In this period 258 operations
      were done. Unilateral significant stenosis found in 159 (61%) patients and
      bilateral serious stenosis or unilateral occlusion in 99 (38.6%) patients. 22.4%
      of the patients who were operated in our department, were waiting for coronary
      revascularisational operation because of angina pectoris. 5.4% suffered from
      vitium and were later undergone cardiac valve operation. By 24% of the patients
      later, electively we performed reconstructional vascular operation on the lower
      limbs. The base of preoperative examinations was cerebrovascular circulational
      insufficiency by almost half of the patients (46.1%). Beside anaesthesiological
      basic examinations, detailed diagnostics (exercised EKG, TTE, coronariography,
      Holter monitor) were done. In the overwhelming majority of the operations we used
      the eversion technique. The surgical interventions were performed in every case
      using non-invasive haemodynamical monitor (transoesophageal doppler ODM-II). Our
      results meet the requirement of the national and international standouts. These
      results prove, that with the help of comprehensive pre-operational examinations
      and preparation, intraoperative monitor and having up-to-date, precise
      operational technique, the international standards can be sustained even treating
      patients with such a high risk.

PMID- 11339086
TI  - [Clinical importance of assessment of collateral capacity in the circle of
      Willis. Benefit of a mathematical blood flow model for the every-day practice of
      vascular surgery].
AB  - Collateral capacity of the Willisian arteries is of clinical importance during
      and after carotid endarterectomies. AIMS: Assessment of cerebral hemodynamics
      using a flow circulation model based on a mathematical formula. PATIENTS AND
      METHODS: Four patients suffering from ischemic stroke in moribund stage were
      investigated using transcranial color-coded duplex sonography. By compressing the
      common carotid arteries, the function of the Willisian collaterals was assessed.
      After the death of the patients, the circles were removed, the diameters and
      lengths of the arterial segments were measured. The data were analysed with the
      mentioned circulation model. RESULTS: The diameters of non-functioning collateral
      arteries were 0.4 mm, while that of the functional ones were 0.7 and 0.8 mm,
      respectively. In the two cases where the anterior communicating arteries did not
      function, a near-critical hemodynamical status was found in the end-arteries.
      This was especially true if the mean arterial blood pressure was 70 mmHg. The
      most critical hemodynamical status developed in case 4, where internal carotid
      occlusion on one side, a contralateral severe carotid stenosis and a non
      functioning anterior communicating artery were observed. CONCLUSIONS: A special
      flow circulation model based on mathematical formula enables the calculation of
      the cerebral blood flow in the different arterial segments of the circle of
      Willis. Further studies are needed to clarify whether the method can be used for
      preoperative modeling of the cross-clamping phase of carotid endarterectomy.

PMID- 11339087
TI  - [Rare case of popliteal artery injury caused by distal femoral exostosis. Case
      report].
AB  - Complications of multiple exostoses occur rarely and articles about it can be
      found occasionally. We found reasonable to report our case because of its rarity.
      A female patient of 17 was under treatment in the Orthopaedic Clinic with
      multiple exostoses. Before her admission to the Clinic, a suddenly, painful
      swelling in the distal-third of the left femur occurred, and then a well detailed
      examination has done (bone radiograph, angiogramm, MR). The examinations arised
      the presence of pseudoaneurysm as a background of the swelling of the soft
      tissue, as well as the possibility of juvenile bone tumor at the same time.
      During the operation we detected a sharp exostosis on the distal medial condyle
      of the femur, which occurred a lesion on the popliteal artery. It was the base of
      forming the pseudoaneurysm. As a conclusion we would like to underline that
      during the attend of such cases, the presence of vascular surgical team is
      necessary.

PMID- 11339088
TI  - [The role of MIBI scintigraphy in the early detection of breast cancer].
AB  - The authors investigate the role of MIBI scintigraphy in the early diagnosis of
      breast cancer. The importance of early diagnosis is emphasized by the fact that
      breast cancer has the highest morbidity and mortality preceding cervical
      carcinoma amongst women. Retrospective examinations were made in case of 42
      patients operated before because of breast cancer in order to examine accuracy of
      both mammography and scintigraphy in comparison with the results of histological
      diagnosis. In these cases sensitivity of scintigraphy turned out to be 69%, while
      its specificity 42%. In cases of mammographical investigations the sensitivity
      proved to be 74% and specificity was 61%. Besides mammography, scintigraphy has a
      very important additional role in the diagnosis of breast cancer. Because of its
      results and costs scintigraphy is not able to take over the mammography's
      dominant position (as a popular diagnostic method) but in selected patients'
      groups it can help to realise tumors as well as to avoid unnecessary operations
      or needle biopsis. Based on our results this method can give significant
      additional information in T1b and especially in T1c states of tumors. Therefore
      this method can be offered as an additional investigation in cases of physically
      realised or mammographically screened, but not-palpable, larger than 1 cm size
      lumps when there is little or moderate risk of malignancy.

PMID- 11339089
TI  - [Changes in the surgical treatment of breast cancer].
AB  - Changes in radicality of breast cancer surgery between 1991 and 2000 are issued
      in this paper. While breast conserving surgery was performed in 26 cases (25%)
      out of 103 in 1991, in the year 2000 165 patients were operated of breast cancer
      and the breast was preserved in 143 cases (87%). These results are partly
      approved by the breast cancer screening performed by physical examination since
      1981 and also by mammography since 1998. The five-year overall survival of
      patients who had been operated between 1991 and 1994 is 90%, the local recurrency
      rate is 6%. Considering these data breast preserving surgery is a reliable
      method.

PMID- 11339090
TI  - [To the Editor in Chief: Internet, information, e-mail and surgical procedures].

PMID- 11339091
TI  - [Quality surgical information on the World-Wide-Web].

PMID- 11339092
TI  - [Differentiated thyroid carcinoma: prognostic factors].
AB  - Factors influencing prognosis and long term outcome of thyroid cancer have been
      described by several groups. It is, however, not clear how the moderate iodine
      deficiency in Hungary can influence the previously described prognostic factors
      by other means than shifting differentiated cancer incidence toward the
      follicular type. Data of 423 out of 472 patients who had been operated on for
      papillary (372) and follicular (100) thyroid cancer between 1971 and 1997 at our
      institution have been analyzed retrospectively. Histological specimens were re
      evaluated and, if needed, revised. Survival curves were compared using the Kaplan
      Meier method. The overall 5 and 10 year survival rates were 93% and 89% for
      papillary, and 92% and 80% for follicular carcinoma. As an independent factor
      extrathyroidal invasion (papillary p = 0.000, follicular p = 0.000), lymph node
      involvement (papillary p = 0.000, follicular 0.011), distant metastases
      (papillary p = 0.000, follicular p = 0.000), and age over 40 years (papillary p =
      0.000, follicular p = 0.000) had negative influence on survival. Multifocality,
      gender, type of surgery (total or near-total thyroidectomy vs. less than near
      total thyroidectomy), and lymphocytic infiltration did not influence survival.
      Iodine intake did not influence survival, however, the incidence of follicular
      cancer was higher in iodine deficient regions. When analyzing the papillary and
      follicular groups separately by Cox regression, extrathyroidal invasion (p =
      0.008), lymph node metastasis (p = 0.004), distant metastasis (p = 0.000), and
      age over 40 years (p = 0.000) were significant predictors in the papillary group,
      while only tumor extrathyroidal invasion (p = 0.019), and distant metastases (p =
      0.000) were significant negative factors in the follicular group.

PMID- 11339093
TI  - [Change in the surgical treatment of benign adrenal gland tumors. Laparoscopic
      adrenalectomy].
AB  - Since 1995 fifty-two patient was operated on the Ist Department of the Surgery
      (DEOEC) due to uni- and bilateral tumor of the adrenal gland. Between May 1999,
      and December 2000 the authors performed 11 transperitoneal laparoscopic
      adrenalectomies (LA). Conversion due to bleeding in 3 cases and due to suspected
      malignancy in 1 case was necessary. This malignant lesion could have been
      resected during the open surgery after only the temporary dissection of the right
      renal vein. Complete resection was carried out in 9 cases. In 2 cases where a
      well circumscribed adenoma or teratoma was visualized, only enucleation was
      performed. The complication rate was low (1 ptx). Blood replacement was not
      necessary. The operation mean time was not any longer in LA compared to the open
      surgical approach. Preoperatively adrenaline (A), noradrenaline (NA),
      metadrenaline (metA), normetadrenaline (normetA) and vanillylmandelic acid (VMA)
      were measured in 24-h urine samples. Adrenal imagery consisted in all patients of
      abdominal computed tomography and in 4 patients adrenal magnetic resonance
      imaging but [131I] metaiodobenzylguanidine (MIBG) and octreotide scintigraphy
      were not performed. CONCLUSION: In the authors experience laparoscopic
      adrenalectomy is absolutely superior to the open surgery for the benign diseases
      of the adrenal gland not bigger than 6 cm. A short, uncomplicated and painless
      postoperative period can be achieved for the patients, with the same efficacy and
      safety compared to the conventional surgery. Enucleation without the whole
      adrenal gland excision is also possible.

PMID- 11339094
TI  - [Complications of laparoscopic cholecystectomy].
AB  - Number of bile duct injuries is rising with the spreading of laparoscopic
      cholecystectomy. Authors analyse the complications in the last 8 years,
      especially the bile duct injuries. During this period 1657 laparoscopic
      cholecystectomies were performed. Complication occurred in 28 cases during the
      intra- and postoperative period (1.68%). Main bile duct injury was detected in 7
      cases (0.42%), while leakage from a Luschka's duct appeared in 10 patients. Three
      bleeding complications, 2 injuries of the duodenum and in 3 cases severe
      intraabdominal infection was observed. Four patients died (0.24%).

PMID- 11339095
TI  - [Surgical treatment of colonic diverticulitis].
AB  - Diverticulitis is one of the most common benign diseases of the colon, which
      usually occurs in elderly. Authors assay the surgical treatment of inflammatory
      complications of colon diverticulitis in the last 19 years. Most frequently
      inflammation occurs, which in lot of cases leads to acute abdominal disease.
      Results of 61 acute and 10 elective operations are analysed. Beside the
      complications and surgical possibilities authors issue the definitive indications
      of elective operation.

PMID- 11339096
TI  - [New technique for surgical treatment of enterovaginal fistula].
AB  - Enterovaginal fistulas most frequently occur following abdominal tumors,
      inflammatory bowel disease and radiation therapy. There is a tendency for
      spontaneous closure, although a surgical intervention is necessary in more than
      50% of the cases. Mortality is between 15-25%. The quality of life is
      significantly worsened by an enterovaginal fistula of a patient already suffering
      from a malignant disease. To relieve the patient from her distressing situation a
      mucous fistula was constructed by exclusion of the small bowel loop participating
      in the formation of the fistula track. Bowel continuity was restored by
      anastomosis. The patient's quality of life improved significantly. This operation
      was performed in three cases without complications. We recommend this procedure
      as an alternative technique to improve our patients' quality of life.

PMID- 11339097
TI  - [The importance of recognizing hereditary non-polyposis colonic carcinoma].
AB  - The clinical diagnosis of hereditary nonpolyposis colon carcinoma (HNPCC) can be
      made in more than 5% of all colorectal cancer cases, depending on the stringency
      of criteria used. The disease is inherited in an autosomal dominant fashion but
      penetrance is lower than 100%. The diagnosis must be verified by the
      demonstration of germline mutations of DNA "mismatch repair" genes. Although yet
      an exception in our national health practice, these tests are routinely applied
      in some centers abroad. The recognition of the syndrome is important since these
      patients can enter a surveillance program and may be cured. The most important
      pertaining information is summarized through the demonstration of our own case.

PMID- 11339098
TI  - [Acute pancreatitis after kidney transplantation].
AB  - Pancreatitis following kidney transplantation was first described by Starzl in
      1964 [19]. The incidence rate of the disease involving severe complications
      ranges from 1.2 to 6.8%. The number of risk factors, besides those of the normal
      population, is increased by a number of other factors, i.e. uremia, disorder of
      lipid metabolism, polycystic kidney, immunosuppressive drugs, cytomegalovirus
      infection, etc. The mortality of acute pancreatitis in a kidney transplant
      patient is, in spite of treatment with the most up-to-date methods, is much
      higher (53-60%) than that for a non-transplant patient. In the period between 27
      June 1991 and 31 December 2000 the number of cadaver kidney transplants performed
      in the Transplantation Division of the 1st Department of Surgery of the Medical
      and Health-Science Centre of the University of Debrecen was 349. During this
      period 9 incidences of acute pancreatitis were found in 8 patients. The frequency
      of incidence was 2.56%. In the present communication we analyse the prognosis of
      9 kidney transplant patients, with special respect to immunosuppression. RISK
      FACTORS: One patient was administered Cyclosporin alone, four were given
      Cyclosporin and Steroids, a further one Cyclosporin, Steroids and Azathioprine,
      the remaining three were treated with Cyclosporin, steroids and Mycophenolate
      Mophetil. In six cases out of nine multiorgan insufficiency (kidney, lung, liver)
      was encountered on presentation, three cases were accompanied by peritonitis. In
      spite of early jejunal nutrition, intensive therapy, antibiotic treatment, CT
      monitoring, if needed, necrectomy and oncotomy, three of our patients died from
      multiorgan insufficiency induced by septico-toxic state (mortality 33.3%). Other
      six patients recovered. CONCLUSIONS: The mortality rate of acute pancreatitis is
      much higher in immunosuppressed patients. The role of the etiological factors is
      not unequivocal in the development of pancreatitis. Nevertheless, all possible
      risk factors have to be taken into consideration when starting the
      immunosuppressive treatment of transplant patients and during their follow-up. By
      optimally adjusting the immunosuppressants we can decrease the risk of
      pancreatitis, however, the prognosis of the diseases, in agreement with the data
      in the literature, cannot be considerably improved even with the most up-to-date
      methods.

PMID- 11339100
TI  - Winners of the MLO 2001 Laboratory Contest. Paying tribute to our unsung heroes.

PMID- 11339101
TI  - Gram's stain: the key to microbiology.
AB  - Gram's stain remains one of the most valuable methods we have for identifying
      isolates accurately and rapidly. Despite our long-standing familiarity with this
      method, it still warrants careful attention every step of the way--from
      preparation and QC of reagents to staining and interpretation.

PMID- 11339099
TI  - [Changes in calcium metabolism after kidney transplantation].
AB  - Prospective study was performed to measure the changes in calcium metabolism
      after kidney transplantation. 139 recipients received calcium substitution (1st
      group) and 81 patients were treated with alfacalcidol (2nd group). Serum Ca, P,
      Mg, alkaline phosphatase (AP) and intact PTH levels were determined before
      transplantation and at 1, 3, 6, 12 and 24 months thereafter in the two groups.
      Femoral and vertebral bone mineral density was measured with bone densitometer at
      the same period. The serum Ca level elevated and the serum P concentration
      decreased significantly in both group. The mean serum Mg and AP concentration
      changed in the normal range after the transplantation. The intact PTH level
      decreased significantly in both group at 2 years following transplantation. The
      intact PTH concentration changed from 17.1 pmol/l to 9.3 pmol/l in the 1st group,
      and it is decreased from 17.7 pmol/l to 7.9 pmol/l in the 2nd group. Bone
      densitometry showed osteoporosis in both group. At 12 months and at 24 months
      after kidney transplantation bone mineral density (BMD) of lumbar spine was 90.8%
      and 86.9% in the 1st group and 85.3% and 81% in the 2nd group. At the same time
      BMD of the femoral region was 84.4% and 85.5% in the 1st group and 82.0% and
      81.3% in the 2nd group. The BMD did not changed significantly in the 1st compared
      to the 2nd group. During this period osteonecrosis was diagnosed in 6 patients in
      the 1st group and in 9 cases in the 2nd group. In conclusion, the serum Ca and P
      levels were in the normal range after kidney transplantation. The alfacalcidol
      treatment significantly decreased the intact PTH concentration compared to the
      calcium substitution. Moderate osteopenia was observed in both groups after the
      transplantation, despite of the administration of alfacalcidol treatment.

PMID- 11339102
TI  - Answering your questions on effective leadership, and improving communication
      skills.

PMID- 11339103
TI  - Easing the transition into multidisciplinary management.
AB  - Beginning a new career in multidisciplinary management can feel overwhelming at
      first. Following the advice in this second part of a 2-part series will help
      relieve the stress and lead you on your way toward professional and personal
      growth.

PMID- 11339105
TI  - HIPAA privacy rule delayed.

PMID- 11339106
TI  - Effect of prolonged marginal ascorbic acid deficiency on lenticular levels of
      antioxidants and lipid peroxide in guinea pigs.
AB  - We examined the effect of prolonged marginal ascorbic acid deficiency of the
      levels of antioxidants and lipid peroxide in lenses of guinea pigs in order to
      clarify lenticular antioxidant status under ascorbic acid deficiency. Male guinea
      pigs aged 4 weeks were given a scorbutic diet (20 g/animal per day) with either
      marginally deficient ascorbic acid (0.5 mg/animal per day) or sufficient ascorbic
      acid (1 g/animal per day) in drinking water for 3 and 6 months. The deficient
      group showed no lens opacity during the administration period. The deficient
      group had 62.3 and 53.9% of lenticular ascorbic acid content in the sufficient
      group at 3 and 6 months of ascorbic acid deficiency, respectively. There were no
      differences in lenticular contents of reduced glutathione and thiobarbituric acid
      reactive substances, an index of lipid peroxidation, between both groups at 3 and
      6 months of ascorbic acid deficiency, while the deficient group tended to have
      higher lenticular vitamin E content than the sufficient group. The deficient
      group had higher serum vitamin E concentration than the sufficient group at 3 and
      6 months of ascorbic acid deficiency. These results indicate that lenticular
      antioxidant status is maintained well in guinea pigs with prolonged marginal
      ascorbic acid deficiency, which may result in no cataract formation.

PMID- 11339107
TI  - Blood micronutrients in Algeria, relationships with sex and age.
AB  - Despite trace elements and vitamins are major public health problems in some
      African countries, there are few studies reporting micronutrient status in North
      Africa. Therefore, it could be interesting to evaluate plasma concentrations of
      vitamin A, E and beta-cartene, along with zinc, copper, selenium erythrocyte
      glutathione peroxidase and superoxide dismutase in Algeria. Volunteers were
      randomly recruited in Constantine, Batna and Mila. Vitamins, trace elements and
      enzymes were measured in the University Hospital of Grenoble. 455 persons were
      included in the study. Subjects were divided in 3 groups: group I: 15 girls and
      12 boys who were 6 to 12.9 years old, group II: 190 women and 192 men 13 to 49.9
      years old, group III: 24 women and 24 men 50 to 65 years old. Plasma
      concentrations of micronutrients and enzymes are close to those commonly observed
      in Europe, except for vitamin A concentrations. Indeed, retinol levels are 30-35%
      lower than those reported in European countries, moreover almost 8% of the
      population showed retinol concentrations less than 1.05 mumol/l. beta-Carotene
      levels were also lower than in the French average population. Ten per cent of the
      population had plasma zinc levels lower than 10.6 mumol/l. Vitamin E, copper and
      selenium status seems satisfactory in Algeria. Vitamin A is not a public health
      problem, however a significant percentage of residents exhibits impaired vitamin
      A levels and may benefit from retinol supplementation. Larger studies are needed,
      and particularly in children, to detect possible higher prevalence of vitamin A
      deficiency in poor socio-economical classes and in inner geographic areas.

PMID- 11339108
TI  - Iron absorption from a breakfast cereal: effects of EDTA compounds and ascorbic
      acid.
AB  - Sodium iron ethylenediaminetetracetic acid (NaFeEDTA) has been recommended for
      food fortification programmes to improve iron status but its performance in
      commercial products has not been evaluated. The effect of EDTA on iron absorption
      from fortified cornflakes, given as part of a typical Western breakfast, was
      determined in a double-blind randomised study with 20 non-anaemic female
      volunteers, using experimentally prepared iron compounds, enriched with 58Fe, and
      faecal monitoring. Five meals were compared: hydrogen reduced iron, hydrogen
      reduced iron plus Na2EDTA (molar ratio EDTA:Fe 1:2), hydrogen reduced iron plus
      NaFe(III)EDTA at two different molar ratios (EDTA:total Fe 1:3 and 1:2), and
      hydrogen reduced iron plus 15 mg ascorbic acid (ascorbic acid:Fe 1.3:1). The iron
      and EDTA compounds were accurately weighed into gelatine capsules and taken with
      unfortified cornflakes, semi-skimmed milk and tea on two consecutive days; the
      iron dose per meal was 3.75 mg. Iron absorption from all five test meals was
      measured in each volunteer with a minimum wash-out period of 2 weeks between
      tests. Geometric mean iron absorption (%) from the 5 tests was 14.1, 17.6, 20.6,
      24.4 and 17.5 respectively (equivalent to 0.5-0.9 mg absorbed iron). There was a
      significantly higher iron absorption from the mixture of reduced iron and
      NaFe(III)EDTA (EDTA:Fe 1:2) than from reduced iron alone (p = 0.014). It is not
      known whether the higher absorption was from reduced iron or NaFeEDTA or both.
      Absorption was not increased significantly with NaFe(III)EDTA (EDTA:Fe 1:3),
      Na2EDTA (EDTA:Fe 1:2) or ascorbic acid (15 mg).

PMID- 11339109
TI  - Dietary factors and body mass index in a group of Iranian adolescents: Tehran
      lipid and glucose study--2.
AB  - OBJECTIVE: To study the prevalence of overweight and obesity in an adolescent
      population in Tehran and to determine possible association with energy and
      nutrient intake and distribution of energy over the day. METHOD: A cross
      sectional study on 177 boys and 244 girls between 10-19 years old was performed.
      Overweight and obesity were defined by using recommended body mass index (BMI)
      cut-off values for adolescents. Total energy intake, percent of energy derived
      from protein, carbohydrate and fat and percent of energy supplied by each meal
      and snack were assessed by means of two 24-hour dietary recalls. RESULTS:
      Prevalence of overweight and obesity was 10.7 and 5.1 in boys and 18.4 and 2.8 in
      girls, respectively. The composition of diet was not different between
      overweight/obese and normal weight subjects. BMI was related with breakfast
      energy percentage in girls (r = -0.18, p < 0.01), with total energy intake in
      boys (r = 0.23, p < 0.01), and with lunch energy percentage in both sexes. In
      boys (r = 0.16, p < 0.05) and in girls (r = 0.22, p < 0.01). CONCLUSION: High
      prevalence of overweight and obesity among adolescents was seen. In boys some
      relationship between total energy intake, distribution of energy over the day and
      BMI was seen. In girls BMI was only related with distribution of energy over the
      day.

PMID- 11339110
TI  - Dietary effects of marine food intake on intestinal and hepatic enzyme activities
      in rats.
AB  - Dietary effects of two diets high in protein from two marine species (Haliotis
      tuberculata and Anemonia viridis) as compared to a high-quality patron protein
      such as casein (or casein supplemented with olive oil) on intestinal and hepatic
      enzymes were studied. After 23 days, the two marine species as diet compared to
      casein increased the disaccharidase and alkaline phosphatase activities. Feeding
      Haliotis tuberculata meal produced a decrease on intestinal leucine
      aminopeptidase activity. The hepatic gamma-glutamyltranspeptidase activity
      decreased slightly in animals fed Haliotis tuberculata meal. Supplementation of
      casein with olive oil tended to decrease the intestinal and hepatic enzyme
      activity.

PMID- 11339111
TI  - Plasma carotenoids in relation to food consumption in Granada (southern Spain)
      and Malmo (southern Sweden).
AB  - We conducted a cross-sectional pilot study on healthy pre-menopausal women (aged
      45-50 years) living in Granada, in the south of Spain (n = 39) and Malmo, in the
      south of Sweden (n = 38) in order to compare their plasma carotenoid levels and
      to investigate the relationship between the differences in food consumption.
      Plasma concentrations of six carotenoids were measured using high performance
      liquid chromatography, habitual diet (at individual level) was estimated by food
      frequency questionnaires and 24-hour diet recalls were used for standardised
      measurement of diet at group-level. We found that women in Granada consumed more
      fruit and vegetables than women in Malmo. Plasma concentrations of beta
      cryptoxanthin, lycopene, zeaxanthin, total carotenoids and alpha-tocopherol were
      higher in Granada than in Malmo, although plasma concentrations of alpha-carotene
      and retinol were higher in Malmo. Both within and between study centres,
      consumption of fruit and vegetables correlated positively with plasma
      concentrations of different carotenoids. The study showed that differences in
      consumption of fruit and vegetables between the two European centres were
      reflected in plasma carotenoid concentrations.

PMID- 11339112
TI  - [Clinical patterns of soft-tissue sarcoma in children].
AB  - INTRODUCTION AND OBJECTIVES: Soft tissue sarcomas are rare mesenchymal neoplasms
      that constitute less than 10% of all pediatric malignancies. Half of these are
      rhabdomyosarcomas, the remaining 50% have a varied and heterogenous histologic
      and clinical patterns (fibrosarcoma, synovial cell sarcoma, extraskeletal Ewing's
      sarcoma, angiosarcoma, liposarcoma, leiomyosarcoma, ...). The purpose of this
      work is to evaluate our clinical experience with soft tissue sarcomas in uncommon
      sites over the past 10 years in order to delimitate the prognostic factors in
      survival and modalities of treatment. MATERIAL AND METHODS: Between 1989 and
      1998, 10 patients were diagnosed with soft tissue sarcomas in uncommon sites and
      treated by us over a total number of 139 pediatric neoplasms (7.19%). Data on
      these patients were obtained from careful review of medical records. Variables
      investigated included histologic findings, tumor size, age at presentation,
      primary site, clinical group, radiologic test performed, surgical treatment,
      radiotherapy and adjuvant chemotherapy, complications and survival rates. Charts
      were registered in database Access. Statistical analysis was performed by the
      SPSS 8.0 statistical program. RESULTS: The following histologic types of these 10
      tumors were identified: 1 hemangiopericytoma in oral cavity, 2 extraosseous
      Ewing's sarcoma, 1 botryoid rhabdomyosarcoma of the bladder, 1 mediastinal
      fibrosarcoma, 1 retroperitoneal rhabdomyosarcoma, 1 paratesticular
      rhabdomyosarcoma, 1 cervical condrosarcoma, 1 alveolar rhabdomyosarcoma and 1
      deltoid rhabdomyosarcoma. 50% were rhabdomyosarcomas and the remaining 50% have a
      variated sarcomatous histologic pattern with a difficult classification. The mean
      age at diagnosis was 7 years (4.6 years accounted for rhabdomyosarcoma alone).
      Surgery with complete excision were performed only in six cases. Adjuvant
      chemotherapy with IVA was followed by radiotherapy only in four patients. All the
      children classified in clinical groups II, III or IV needed 2nd. line regimens of
      chemotherapy. Three patients died in the follow-up instead of the multimodal
      treatment. Survival ranged from 6 months to 9 years (mean 4 years). CONCLUSIONS:
      The impact of surgical resectability on outcome in these tumors has been clearly
      demonstrated over other factors like histologic appearance. Distant metastasis
      are infrequent but local recurrence are a constant in all cases with incomplete
      surgical resection. Based on those facts we could advanced an adequate approach
      to this kind of neoplasms: 1) wide complete surgical resection is mandatory; 2)
      radiotherapy will only be necessary if margins of resection cannot control the
      local disease, and 3) chemotherapy have not clearly demonstrated his benefits as
      adjuvant therapy in clinical group I lesions but his employ is recommended in all
      cases because of the poor prognosis due to local recurrence.

PMID- 11339113
TI  - [Current status of pediatric lung transplantation].

PMID- 11339114
TI  - [Diaphragmatic paralysis: pathology at the reach of the pediatric surgeon].
AB  - The phrenic nerve is the only motor nerve in the diaphragm. The injury will lead
      to a diaphragmatic paralysis or eventration with paradoxical movements during
      breathing. The aim of this review is to analyze the diagnostic criteria, surgical
      indications, and the patients that are not treated by surgery. We review 53 cases
      with diaphragmatic pathology in the last 5 years; 19 females and 20 males. One
      was a diaphragmatic rupture, 13 were diaphragmatic hernias, and 39 had
      diaphragmatic paralysis. Diaphragmatic paralysis was diagnosed by fluoroscopy in
      97%, electromiography 5.1% or ultrasounds. The ethiology was 64% after cardiac
      surgery and 10% after thoracic oncologic surgery. The age at diagnosis was less
      than 1 month in 41% cases. In 29 patients the paralysis was well tolerated and
      were extubated between 24 h and 4 days after the diagnosis, frequently was in the
      first 48 h. 4 patients need a traqueostomy and 2 went to another hospital. In 5
      we performed a diaphragmatic plication because the inability to be extubated or
      the persistence of respiratory distress. The paralysis was demonstrated by
      fluoroscopy. 2 patients are asymptomatic, 2 are in mechanical ventilation and 1
      died (sepsis). The most frequent cause of diaphragmatic paralysis was related to
      cardiac or thoracic surgery. In general, is well tolerated, almost asymptomatic,
      the patients were extubated between 24 or 48 h. In pediatric population they are
      few cases that need surgical treatment. The patients that we operated on were
      less than 2 months old, because is at that age were the repercussion is more
      important. We must follow strict criteria, without precipitation for the surgical
      indications.

PMID- 11339115
TI  - [Intestinal transplantation. First experience in Spain].
AB  - We present the first case of intestinal transplant (IT) performed in Spacin. CASE
      REPORT: 28 months old boy with secretory diarrhea since the first month of life,
      diagnosed of microvillous inclusion disease (MID). He is on total parenteral
      nutrition (TPN) and had suffered of multiple episodes of catheter related sepsis
      with lost of standard venous access. An isolated small bowel transplant from a
      cadaveric donor was performed at the age of 3 years. The native ileocaecal valve
      and colon were not removed. RESULTS: Enteral feeding was started in the 2nd. week
      after the IT. On the 25th day he was off TPN. Since the 77th day, he eats regular
      foods by mouth. At the 6th month post IT the ileostomy was closed. Among the
      complications, he suffered a rotavirus infection on the 38th post IT day and an
      episode of mild rejection responsive to methil-prednisolone bolus. CONCLUSIONS:
      The IT is a therapeutic option that can be already offered with possibilities of
      success in our country. Although the colonic enterocytes express MVD, the
      recipient ileocaecal valve and colon can be preserved.

PMID- 11339116
TI  - [Fascia lata transplant from cadaveric donor in the reconstruction of abdominal
      wall defects in children].
AB  - INTRODUCTION: Abdominal wall closure is not possible in large congenital defects,
      even after extensively stretching in to enlarge its capacity. The skin coverage
      is usually adequate but the aponeurotic defect has to be closed temporally using
      synthetic patches. The use of these materials leads to increase complication such
      as infection, fistula formation and extrusion. In addition a second operation is
      required to remove the material and to perform a definitive closure. The role of
      fascia lata in reconstruction of abdominal wall is well established as free
      grafts, pedicled flaps or free flaps. Bank cadaveric fascia lata is used
      extensively in neurosurgical, ophtalmological, orthopaedic and urogynecological
      procedures. This is the first description of the use of cadaveric fascia lata for
      the closure of large abdominal wall defects. CASE REPORTS: We present two cases
      of congenital diaphragmatic hernia. The first patient was a newborn who presented
      the impossibility to close the fascia, that was salvaged by a teflon patch. Five
      months later the wound opened, leaving the mesh exposed that had to be removed. A
      cadaveric fascia lata patch was used to cover the defect, closing the skin
      satisfactorily. The second case was a two days newborn. We performed the
      diaphragmatic closure, and the aponeurotic defect was closed using cadaveric
      fascia lata. RESULTS: Cosmetic and functional appearance are satisfactory in both
      cases and no complications have been seen. CONCLUSION: Fascia lata patches are
      revascularized in the abdominal wall and incorporates into receptor tissue. They
      have the following advantages with respect to synthetic materials: First, the
      risk of complications is lower. Second, their removal is not necessary. Finally,
      no intraperitoneal adhesions occur. The risks of disease transmission and
      rejection are minimized by the Centro Comunitario de Transfusiones donor
      selection and processing of the cadaveric fascia lata.

PMID- 11339117
TI  - [Treatment of caustic stenosis of the esophagus with self-expanding devices].
AB  - Caustic stenosis is a serious problem in children due to its complicated
      resolution and implications in important areas like nutrition, as well as the
      child's tolerance to the measures taken to correct them. After dealing
      extensively with this problem over the last twenty five years, always from a
      conservative approach using traditional methods like dilatations, we believe we
      have found a technique that brings together all the necessary conditions to
      achieve a favorable and definitive solution. Our ideal goal to achieve a device
      that provides a well-tolerated permanent esophageal expansion during the scarring
      process, also permitting normal swallowing, seems to have been reached through
      the use of the new generation of silicone stents. The authors present their
      experience in the first seven cases of caustic stenosis treatment through the
      placement of silicone stents, describing a precise placement technique while
      establishing a standard protocol for the use of these devices.

PMID- 11339119
TI  - [Congenital esophageal obstruction caused by complete mucous membrane: a clinical
      case].
AB  - The authors report a case of membranous atresia of the esophagus. Diagnosis of
      this rare malformation was made intraoperatively, and resection and primary
      anastomosis were performed immediately. A brief review of the literature is
      included on the various types of esophageal atresia.

PMID- 11339118
TI  - [Severe caustic injuries of the esophagus: when to replace the esophagus].
AB  - From June 1985 to May 1998, 20 patients have been treated in our hospital by
      esophageal dilatations due to serious esophageal caustic stenosis. A
      retrospective analysis of these 20 patients was performed, evaluating age, sex,
      causative agent, number and time of dilatations, iatrogenic esophageal
      perforations, gastroesophageal reflux (GER) and psychological and social
      consequences. Follow-up has ranged from 1.5 to 14.5 years (mean = 8.07 years).
      The mean age at the time of accidental swallow was 42.2 months. The causative
      agent was dishwashing detergent in 11 patients and caustic soda in 9 patients.
      The mean of dilatations needed was 19.1 and the average duration of dilatations
      was 24.7 months. Seven patients had esophageal perforation during dilatation and
      none of them required surgical treatment. All patients had improvement of
      swallowing and an easier esophageal dilatation afterwards. Oral contrast studies
      demonstrated distortion of the esophago-gastric junction in the majority of
      patients. Ten patients were screened for GER with 24-hour esophageal pH
      monitoring in the first year postburn and it was pathological in 5. Antireflux
      surgery was carried out in 4 patients with a conspicuous improvement following
      surgery. Dilatations proved successful in 16 patients in less than two years, and
      in more than two years in 3 patients. The authors conclude that the majority of
      children with esophageal caustic stenosis can be managed successfully by
      esophageal dilatations, even with dilatation periods longer than two years or
      when an esophageal perforation occur during the procedure. The paramount
      importance of early diagnosis and treatment of GER is stressed.

PMID- 11339121
TI  - [Retroperitoneal cystic lymphangioma in childhood].
AB  - Lymphangiomas are very common neoplasms in infancy. However, a retroperitoneal
      location is seldom observed. We present the case of a male with a history of
      chronic recurrent pain over a period of several years. An X-ray showed a calcic
      density in the left upper abdominal quadrant; the histological study revealed it
      to be a mixoid cystic lymphangioma. Clinical presentation varies greatly from an
      asymptomatic mass to serious complications. In order to correctly diagnose of
      these neoplasms it is essential to carry on ultra sound and CT examination
      although a simple abdominal X-ray may show calcifications as the one presented
      here. Treatment is always surgical and a complete extirpation should be
      performed, unless vital structures were are involved. Treatment with laser,
      fibrin and sclerotherapy have also been used. CONCLUSION: In spite of being
      benign neoplasms we believe they should be removed to confirm diagnosis and avoid
      possible complications.

PMID- 11339120
TI  - [Effect of various trophic factors on bacterial translocation in experimental
      short bowel syndrome].
AB  - Massive bowel resection triggers an adaptive process in the remaining intestine
      in spite of which, bacterial translocation (BT) is frequent under these
      conditions. Several trophic factors, including growth hormone (GH), epidermal
      growth factor (EGF) and insuline (INS) are involved in the process of adaptation
      in short bowel syndrome (SBS). However, the effect of GH, EGF or INS on BT has
      not been investigated experimentally. The aim of the study was to test the
      hypothesis that GH, EGF or INS administration prevents BT in rats with SBS
      receiving only parenteral nutrition (PN). Thirty-seven adult Wistar rats
      underwent central venous cannulation and were randomly assigned to one of two
      groups receiving for ten days four treatment regimes: PN group (N = 10) fasting,
      all-in-one PN solution (300 mL/kg/24 h, 280 kcal/kg/24 h), 80% gut resection
      including ileo-cecal valve. GH group (N = 9) fasting, same PN regime and
      resection plus GH (1 mg/kg/d, s.c.). EGF group (N = 9): same PN regime and
      resection plus EGF (150 microgr/24 h, e.v.) INS group(N = 9): same PN regime and
      resection plus INS (1 U.I./100 g/24 h s.c.) At the end of the experiment the rats
      were exanguinated and mesenteric lymph nodes and samples of systemic and portal
      blood were obtained and cultured. Several samples of full-thickness jejunal wall
      were taken for measuring cell proliferation index (PCNA) and mucosal thickness.
      Jejunal mucosal thickness increased by 30%, 28% and 29% and PCNA index by 21%,
      20% and 25% in GH, EGF and INS, treated rats respectively in comparison with
      those treated with PN alone. However, contrary to our expectations, BT expressed
      by positive culture of intestinal germs in systemic blood was demonstrated
      respectively in 44%, 40% and 28% of GH, EGF and INS animals, respectively, and in
      0% of PN-only rats. Although exogenous GH, EGF or INS improves gut mucosal
      structure in rats with SBS treated with PN, it seems to increase rather than
      decrease mucosal permeability to intestinal germs in them.

PMID- 11339122
TI  - [Usefulness of ultrasonography in the initial assessment of blunt abdominal
      trauma in children].
AB  - Abdominal injuries are frequent in children, and the early assessment is the best
      guaranty for an accurate management. Although computed tomography (TAC) has been
      considered the diagnostic modality of choice for children with blunt abdominal
      trauma, is a costly radiological test that requires the patients be stable and
      sedated. The aim of this study is to evaluate the usefulness of abdominal
      ultrasonography, a quick, non-invasive technique, of low cost, and repeatable,
      during the initial assessment of these patients, arguing about the possibility of
      replace TAC in the detection of intra-abdominal posttraumatic injury. A
      retrospective case note review was carried out on the 22 children of less than 8
      year-old admitted with blunt abdominal trauma to the Pediatric Surgery Section of
      our institution between 1991 and 1999. The most common mechanism of injury has
      been the motor vehicle accident (63.63%). All were initially evaluated with
      ultrasonography and those with any abnormal ultrasonographic findings (free
      intraperitoneal fluid, intra-abdominal organ injury) were further evaluated with
      computed tomography and/or repeated sonographies. Sensitivity, specificity,
      positive predictive value, negative predictive value, and accuracy o the
      diagnostic methods, have been evaluated. This investigation found abnormalities
      in 17 patients, 70.59% of whom have been managed conservatively. The accuracy of
      the abdominal ultrasound in the diagnosis of intra-abdominal injury was 77.27%,
      with a 82.35% sensitivity, 60% especificity, 87.5% positive predictive value, and
      50% negative predictive value. The accuracy of the TAC in the diagnosis was
      93.75%. The sensitivity, specificity, positive predictive value, and negative
      predictive value of the TAC were 92.85%, 100%, 100%, and 66% respectively. We
      conclude that TAC is the imaging modality of choice in children with severe
      abdominal trauma but ultrasonography is a reasonable technique to arouse
      diagnostic suspicion, that can avoid additional tomographic studies. Abdominal
      computed tomography must be reserved for the hemodynamically stable children with
      anormal ultrasonographic findings or with suspected injuries by a clinical
      evolution that gone unnoticed in the previous study.

PMID- 11339123
TI  - [End-of-life decision in the perinatal period: a debate for professionals, a
      question for society].

PMID- 11339124
TI  - [Current indications for cisapride].

PMID- 11339125
TI  - [Blood transfusion despite early use of erythropoietin: failure or limit of
      therapy? Annual cohort study of premature infants weighing less than 1500 g].
AB  - STUDY: Prospective, observative study. SETTING: Neonatal intensive care unit in a
      university tertiary care hospital. AIMS: 1) Assessment of blood transfusion
      requirement. 2) Demonstration of haematocrit and hemoglobin level difference at
      birth between transfused and non-transfused infants. 3) Assessment of iron mass
      before and after early iron supplementation. POPULATION: All premature infants
      without cardiopathy, surgical diseases, hemolysis or haemorrhage, at less than 30
      weeks of gestational age or less than 32 weeks, weighing less than 1,500 grams,
      with respiratory distress syndrome admitted into the unit during the year 1998,
      were included in the study. Each received erythropoietin (750 U.kg-1.wk-1) with
      intravenous iron supplements from day 5 (0.017 mmol.kg-1.d-1), then orally (0.17
      mmol.kg-1.d-1). RESULTS: Seventy-nine premature infants were included in this
      study. 1) Sixty-seven percent of the transfusions occurred during the first 14
      days of life. 2) Haematocrit and hemoglobin levels at birth were significantly
      different between transfused and non-transfused infants (P < 0.001) and remained
      different for infants of less than 28 weeks (P < 0.01). 3) After six weeks of
      iron supplementation (mean 0.31 mmol/kg), the ferritin level had significantly
      decreased in the non-transfused (P < 0.001) and transfused population (P < 0.01).
      CONCLUSION: Increasing the haematocrit and the hemoglobin levels at birth, for
      example by placentofetal transfusion, could decrease the number of early
      transfusion. Early intravenous iron supplementation had no side effects but did
      not maintain iron levels.

PMID- 11339126
TI  - [Adolescents at the Lenval's children's hospital emergency unit in Nice in 1999].
AB  - OBJECTIVE: The goal of this survey was to investigate adolescents' health through
      their utilization of a pediatric emergency unit. METHODS: Prospective survey
      performed one week of each month in 1999 concerning the adolescents' (12 to 18
      years) visits to the Lenval's children emergency care unit in Nice. RESULTS:
      During the study period, 1,096 adolescents were examinated and accounting for
      18.6% of the children admitted in the year. The main reasons for visits were
      injury-related visits (55.5%), non-accidental somatic complaints (38.7%),
      psychiatric disorders (5.5%), and psychosocial problems (0.4%). Most adolescent
      visits (68.6%) were not severe emergencies requiring hospital technical equipment
      support; about one-third of the visits (28.6%) were non urgent consultations;
      severe emergencies were fewer than 1%; there was no death. Compared with the
      other pediatrics age groups, adolescents more often used the hospital technical
      equipment (65.1% vs 45.4%), required a longer visit (62 +/- 33 vs 57 +/- 37 min),
      and had a higher hospitalization rate (13.4% vs 10.1%). CONCLUSIONS: Adolescent
      emergency care requires multidisciplinary skills, such as traumatologic,
      gynecologic, psychiatric, and psychosocial compentence. Two units, absent at
      Lenval at the time of this survey, seem to be important for good care: space for
      very short hospitalization in the emergency unit and an adolescent-specific unit
      in the pediatric ward.

PMID- 11339127
TI  - [Experimental study of changes in FiO2 during manual ventilation].
AB  - Discrepancies exist in the recommendations about the oxygen flow to deliver
      during manual ventilation. The aim of the present study was to determine the
      effects of ventilatory frequency (FR), inspiratory pressure (P) and oxygen flow
      on the concentration of the delivered oxygen (FiO2) to obtain FiO2 near 1.
      MATERIAL AND METHODS: Experimental study with self-inflating resuscitation bag
      (Ambu with oxygen reservoir) tested on a mono-compartmental test lung (resistant
      tube and elastic bag [Draeger]; characteristics: compliance = 0.6 mL/cmH2O;
      resistance = 85 cmH2O.L-1.s-1). Protocol 1: six neonatologists ventilated this
      model as if they were ventilating premature newborn infants with RDS at various
      ventilatory rates from 30 to 120 bpm and at various oxygen flows (from 2 to 12
      L/min). Tidal volumes (Vt), inspiratory times (Ti), P and FiO2 were recorded
      continuously during the study. Protocol 2: a graduated manometer was added to
      visualize pressure. The same protocol was then applied. RESULTS: Protocol 1
      (without visual control of the pressure): increase in oxygen flow delivered with
      the Ambu increases the FiO2 values (P < 0.0001); the higher the ventilatory
      frequency, the lower the FiO2 (P < 0.0001). The mean value of delivered FiO2 was
      related to the operator (extreme: 47-86%) (P < 0.001). Multivariate statistical
      analysis showed that O2 flow, ventilator rate and operator modulated
      independently the FiO2. Ti and Vt did not change the FiO2. Protocol 2 (with
      visual control of the pressure: the mean inflating pressures were less than those
      obtained without visual control of the pressure (26 vs 40 cmH2O respectively; P <
      0.05). FiO2 was independent of O2 flow and ventilatory rate. CONCLUSIONS: A
      special device for continuous visual control of airway pressure is recommended
      during neonatal manual ventilation. It prevents ventilatory rate-induced FiO2
      fluctuations and overdistention.

PMID- 11339128
TI  - [Neonatal hemorrhagic syndromes].
AB  - PURPOSE: The purpose of our study was to clarify the frequency of these causes.
      PATIENTS AND METHODS: Retrospective study using reports of newborns in the
      neonatal unit in Sousse (Tunisia) from 1991 to 1996, hospitalized for hemorrhagic
      syndrome defined by bleeding, exteriorized or not, whatever its importance,
      severity, causes and the associated clinical and biological disorders. Isolated
      meningeal hemorrhages, limited cutaneo-mucous hemorrhages (conjunctival
      hemorrhages, bruises), and genital crises of the newborn, were excluded. RESULTS:
      One hundred and fifty-five hemorrhagic syndromes were observed from 7,128 newborn
      infants (2.17% of hospitalization). Sex ratio was 1.42. Prematurity rate was
      35.7%. The Apgar score was < 7 at one minute in 40.7% of cases. Disorders
      associated with hemorrhagic syndromes were observed in 118 newborn infants
      (76.1%) with a predominance of neonatal infections (35.6%). The etiology of
      neonatal hemorrhages was specified in 93% of cases: newborn hemorrhagic disease
      (27.7%), disseminated intravascular coagulation (27.1%), isolated
      thrombocytopenia (9%), digestive lesions (13.5%), and obstetrical trauma (2.6%).
      CONCLUSION: The frequency of the newborns hemorrhagic syndromes underlines the
      need for its systematic prevention by vitamin K in the antenatal period to the
      mother and after birth to the newborn.

PMID- 11339129
TI  - [Pigmented villonodular synovitis. Diffuse and localized forms in children].
AB  - Pigmented villonodular synovitis (PVS) is characterized by a locally aggressive
      synovial proliferation that engenders progressive destruction of cartilage and
      bone. Two cases, a diffuse and a localized form, are reported. CASE REPORT: 1) A
      9.9-year-old boy followed up for a popliteal cyst presented with chronic
      arthritis of the left knee. Aspiration yielded a bloody synovial fluid. MRI
      showed a heterogeneous synovial process with decreased signal in both T1- and T2
      weighted images. The diagnosis of PVS was made on histology of an excisional
      biopsy. A complete open synovectomy was then performed. 2) A 13.8-year-old boy
      had a palpable mass on the internal side of the right patellofemoral joint. MRI
      showed a heterogenous mass with areas of hypointensity on all spin echo sequences
      corresponding to hemosiderin deposits suggestive of PVS. Surgical excision of a
      reddish-brown circumscribed lesion was performed. Diagnosis of PVS was made at
      surgery and confirmed by histologic examination. CONCLUSION: PVS diagnosis is
      frequently delayed due to nonspecific symptoms. Bloody fluid aspiration and MRI
      are valuable tools for early diagnosis. Treatment is surgical: extensive
      synovectomy for the diffuse form, excision of the lesion for the localized form.

PMID- 11339130
TI  - [Tetralogy of Fallot in monozygotic twins].
AB  - The causative mechanisms of congenital heart defects remain unclear and little is
      known about the respective implication of chance, genetics and environment,
      though recent findings in molecular biology may provide further insight into
      understanding the pathophysiologic basis of congenital heart diseases. CASE
      REPORT: We report the exceptional but significant case of monozygotic twins both
      affected by tetralogy of Fallot, for whom prenatal diagnosis ruled out 22q11
      microdeletion. CONCLUSION: We discuss how far this observation is consistent with
      the latest hypothesis, which emphasizes the leading role of genetic factors.
      Several genes indeed, either separately or in combination, could be responsible
      for those defects, even if other influences may still come into play.

PMID- 11339131
TI  - [Fibroblastic rheumatism: a case report].
AB  - Fibroblastic rheumatism is a rare entity. Nineteen cases were reported in the
      literature, and among them, only one in a child. CASE REPORT: Cam. (born August
      19, 1988) had an onset of disease in October 1996 with nodules on the MCP and
      PIP, elbows and tibia, with partial improvement after three months. In April
      1997, she suffered from arthralgia and stiffness of both wrists, and then of the
      big toes. X-rays showed destructive and erosive lesions on both wrists and on the
      PIP of the second and third fingers and the big toes. Laboratory investigations
      disclosed normal values for ESR and CRP and negative results for ANA and RF. The
      diagnosis of fibroblastic rheumatism was based on the typical histologic pattern
      of a nodule. The treatment associated colchicin and rehabilitation. In August
      1998, the wrists' stiffness began to improve, though the big toes remained
      totally stiff. The radiologic erosive lesions did not show progress. COMMENTS:
      The diagnosis of fibroblastic rheumatism is based on the histologic pattern of
      the nodules. The erosive evolution of the arthropathies is infrequent (8/15 cases
      in adults). Juvenile onset is very rare; only one case has been reported, in a 10
      year-old boy. The mechanism of the disease remains unknown. As it is very rare,
      the therapeutic strategies are not well established. CONCLUSION: This disease
      should be considered among the causes of juvenile arthritis with erosion.

PMID- 11339132
TI  - [Pseudotumoral presentation of cat scratch disease].
AB  - BACKGROUND: A frequent cause of chronic benign lymphadenopathy, cat-scratch
      disease (CSD) occurs mainly in children and young adults. Bartonella henselae is
      the agent responsible for CSD. The most common symptoms of the disease are
      regional lymphadenopathy and fever. Atypical forms occur in about 10% of
      patients; among them, CSD may initially present as a tumor. CASE REPORT: A 4-year
      old child developed a 'tumor' of the arm with fever. The values of white blood
      cell count and CRP were normal. Ultrasonography, MRI and arteriography did not
      contribute to the diagnosis, which was established on histologic examination and
      serologic test for infection with B. henselae. The outcome was favorable with
      antibiotic treatment. CONCLUSION: In case of tumor of the limbs, cat-scratch
      disease should be searched for.

PMID- 11339133
TI  - [Dietary recommendations for pregnant women affected with phenylketonuria].
AB  - Prevention of embryopathy due to maternal phenylketonuria is possible thanks to a
      maternal-specific low-phenylalanine diet, which has to be started before
      conception and followed during the whole gestation. The setup of this diet
      implies knowing the recommended dietary allowances for normal pregnant women as
      well as for women with nutritional deficiencies. Women with phenylketonuria must
      be considered at risk for nutritional imbalance for two main reasons. First, most
      adult women with phenylketonuria have been on a vegetarian diet for many years
      without protein substitutes or medical control. Secondly, the strict diet for
      pregnant women with phenylketonuria may induce anorexia or nutritional deficits
      if it is not well tolerated or understood. Protein, iron, calcium, selenium,
      vitamin B 12 and caloric intakes are the most sensitive parameters. Close
      cooperation with an experienced medical and dietician team is required.

PMID- 11339134
TI  - [Ethical dilemmas in the perinatal period: guidelines for end-of-life decisions].
AB  - According to several recent surveys, around 50% of the deaths occurring nowadays
      in French neonatal intensive care units result from a medical decision. This has
      led French neonatologists to set up guidelines for end-of-life decisions and
      practice in the perinatal period, which are presented in this paper. It covers
      definitions, clinical situations, ethical principles, obligations of the medical
      and nursing staff, and specific conditions where dilemmas occur.

PMID- 11339135
TI  - [Evaluation and management strategies for acute pain in ambulatory care of
      children aged 1 month to 15 years. Text of the recommendations of the National
      Agency for Health Accreditation and Evaluation].
AB  - This paper is the text of recommendations drawn up by a working group of the
      French national agency, the Agence nationale d'accreditation et d'evaluation en
      sante (ANAES), on the management of acute pain in ambulatory care of children.

PMID- 11339136
TI  - [Entry into sexuality and its hazards].
AB  - It is estimated that approximately 20% of adolescents (girls and boys) have their
      first intercourse experience before 15 years of age. Between 17 and 18 years,
      approximately 50% have had at least one complete sexual intercourse, and more
      than one-third have developed a long-lasting relationship. Girls often have an
      affective link associated with sexual activity. This paper deals with adolescent
      psychosexual maturation, gender differences, and motivations and feelings
      concerning their first intercourse experiences.

PMID- 11339137
TI  - [Proposal for post-transfusional survey of neonates].

PMID- 11339138
TI  - [Benign transient hyperphosphatasemia in children].

PMID- 11339139
TI  - [Evaluation of exocrine pancreatic function in term and premature infants during
      the first week of life by fecal elastase 1 assay].

PMID- 11339140
TI  - [Hyperammonia, hypoglycemia and thrombocytopenia in a newborn after materanl
      treatment with valproate].

PMID- 11339141
TI  - [Vitamin D status of pregnant Palestinian women].

PMID- 11339142
TI  - [Open letter from an urban pediatrician to his hospital colleagues].

PMID- 11339143
TI  - Radiologic placement of hemodialysis central venous catheters: a practical guide.

PMID- 11339144
TI  - Percutaneous renal access: how I do it.

PMID- 11339145
TI  - Percutaneous removal of pulmonary artery emboli with Hydrolyser catheter in pigs.
AB  - OBJECTIVE: To evaluate the efficacy and safety of the Hydrolyser catheter for
      percutaneous treatment of massive pulmonary embolism in pigs. MATERIALS AND
      METHODS: Twelve pigs, each weighing between 55 kg and 89 kg, were used.
      Radioopaque 9 cm x 0.8 cm and 4.5 cm x 0.8 cm clots, produced by mixing pig blood
      with iodinated contrast agent in vacutainers, were injected via the jugular vein
      until central pulmonary embolism (main and proximal lobar arteries) was obtained
      with significant systemic and pulmonary hemodynamic modifications. From a femoral
      approach, the 7-French Hydrolyser thrombectomy catheter was run over a 0.025-inch
      (0.64-mm) guide wire to remove the pulmonary emboli. Hemodynamic, gasometric and
      angiographic monitoring was performed before and after treatment. The procedure's
      safety and completeness of emboli removal was assessed by cardiopulmonary
      autopsy. RESULTS: Three of the 12 pigs died during embolization. Thrombectomy was
      therefore performed in 9, and central emboli could be obtained in 7 of the 9. The
      Hydrolyser could be manipulated only in central pulmonary arteries and could
      aspirate only central emboli in 5 of the 7 pigs that had them. Despite minimal
      angiographic improvement seen in these 5, there was no significant hemodynamic
      and gasometric improvement after treatment. The procedure induced an increase in
      free hemoglobin blood levels. Autopsies revealed an average of 2 endothelial
      injuries per pig (mainly adherent endocardial thrombi) in both nontreated (n = 3)
      and Hydrolyser-treated (n = 9) groups. CONCLUSION: The Hydrolyser thrombectomy
      catheter can be promptly positioned and easily steered in central pulmonary
      arteries. It can be used to partially remove central emboli, but not peripheral
      pulmonary emboli. Most of the injuries observed may not have been strictly
      related to Hydrolyser use. The pig might not be a suitable animal model for
      treatment of massive pulmonary embolism.

PMID- 11339146
TI  - Answer to case of the month #81. Tracheobronchial papillomatosis with spread to
      pulmonary parenchyma and the development of squamous cell carcinoma.

PMID- 11339147
TI  - Answer to case of the month #82. Insulinoma of the head of the pancreas.

PMID- 11339150
TI  - Interventional radiology in Canada: will it flourish, or is this the beginning of
      the end?

PMID- 11339151
TI  - The current status of interventional radiology in Canada: results of a survey by
      the Canadian Interventional Radiology Association.
AB  - OBJECTIVE: To evaluate the current status of interventional radiology in Canada.
      METHODS: A questionnaire was sent to 28 Canadian interventional radiologists
      (defined as a physician who performs any type of interventional procedure,
      including biopsies, but excluding interventional neuroradiology) practising in
      both tertiary and community hospitals in the major centres in all provinces
      except Prince Edward Island. RESULTS: Twenty-two (79%) of 28 surveys were
      completed and returned, providing data about 86 interventional radiologists
      (IRs). IRs were performing almost all of the following procedures at their
      institutions: inferior vena cava filter placement, venous angioplasty, dialysis
      fistula angioplasty, diagnostic and therapeutic pulmonary and bronchial artery
      procedures, diagnostic and therapeutic procedures of the lower extremity and
      renal arteries, percutaneous abscess and biliary drainage procedures,
      percutaneous nephrostomy, and fibroid embolization. A second group of procedures,
      performed by both IRs and non-radiologists in most institutions, included: all
      types of central venous catheter placements, pleural drainage, and gastrostomy
      tube placement. Procedures not being performed by anyone in a number of
      institutions included: dialysis graft thrombolysis, varicocele embolization,
      transjugular intrahepatic portosystemic shunts, palliative stenting of the
      gastrointestinal tract, fallopian tube recannalization, and liver and prostate
      tumour treatments. The factors most often limiting the respondents' ability to
      provide a comprehensive interventional service were the interventional radiology
      inventory budget and the availability of interventional radiology rooms; 50% of
      respondents indicated the number of available nurses, technologists and IRs was
      also an important limiting factor. CONCLUSION: IRs in Canada still play a major
      role in many of the most commonly performed procedures. However, limited
      availability of resources and personnel in many institutions may be hampering the
      ability of IRs to develop new procedures.

PMID- 11339152
TI  - Pulmonary arteriovenous malformations: overview and transcatheter embolotherapy.
AB  - Pulmonary AVMs are most commonly seen in patients with HHT, a fascinating multi
      system disorder that is all too often underdiagnosed and undertreated. Not only a
      medical curiosity, HHT is a serious condition that causes substantial morbidity
      and mortality. Pulmonary AVMs are effectively and safely treated by transcatheter
      embolotherapy.

PMID- 11339153
TI  - Prevention of breastfeeding tragedies.
AB  - Although successful breastfeeding confers compelling advantages to infants and
      mothers, inadequate breastfeeding can result in critical infant failure-to-thrive
      and hypernatremic dehydration. Potential catastrophic infant outcomes can occur
      when enthusiastic promotion of breastfeeding outpaces necessary support services
      and management. Such cases often involve underlying maternal and infant
      breastfeeding risk factors, made deadly by parental and professional
      misconceptions and knowledge deficits or health care system failures. An early
      follow-up visit a few days after discharge allows at-risk infants to be
      identified before they lose excessive weight and at a time when intervention can
      easily correct most breastfeeding problems before they become complicated by
      insufficient milk. Those who enthusiastically promote breastfeeding for its many
      health benefits must confront the reality of breastfeeding failure and implement
      necessary changes in medical education and support services to foster successful
      outcomes in breastfed infants.

PMID- 11339154
TI  - Incorporating breastfeeding care into daily newborn rounds and pediatric office
      practice.
AB  - Integrating breastfeeding care into pediatric practice and thought process
      results in improved breastfeeding outcomes for patients and significant
      professional satisfaction for pediatricians. Meeting a family's expectation to
      help them succeed in their desire to breastfeed their infants is rewarding.
      Current knowledge regarding the appropriate care of the breastfed infant
      immediately after birth provides an engaging opportunity to reframe ideas
      regarding good newborn care. Whatever may have previously been thought regarding
      newborn care, the true objectives are to maintain optimal physiologic parameters
      and optimize neurophysiologic and behavioral homeostasis in transitional infants.
      The goal is a thriving, eagerly breastfeeding newborn infant and a comfortable
      mother with an abundant milk supply within the physiologically anticipated time
      frame. In the office setting, supporting the ongoing success of the breastfeeding
      is a natural extension of the preventive health care activities that are the
      cornerstone of general pediatrics. Facilitating parents' plan to breastfeed their
      infants by incorporating good breastfeeding care into daily practice routines is
      professionally satisfying, enhances the well-being of pediatric patients, and
      enriches the experience of practicing general pediatrics.

PMID- 11339155
TI  - Management of common breastfeeding issues.
AB  - Breastfeeding provides ideal nutrition, growth hormones, and antibodies that
      change over time as growing infants' and children's needs change and provides
      these inexpensively, with no harm to the environment. Breastfed infants are
      healthier than other infants overall, and research indicates that the health
      benefits may continue on into adulthood. Increasingly, women are choosing to
      initiate breastfeeding in the hospital, but the attrition starts early and is
      dramatic. For women to meet their breastfeeding goals, physicians must not only
      give lip service to "breast is best" but also become knowledgeable in
      breastfeeding management and actively promote breastfeeding in their practices
      and in their communities.

PMID- 11339156
TI  - How to assess slow growth in the breastfed infant. Birth to 3 months.
AB  - Pediatricians must monitor early breastfeeding to detect and manage breastfeeding
      difficulties that lead to slow weight gain and subsequent low milk production.
      Infant growth during the first 3 months of life provides a clear indication of
      breastfeeding progress. Healthy, breastfed infants lose less than 10% of birth
      weight and return to birth weight by age 2 weeks. They then gain weight steadily,
      at a minimum of 20 g per day, from age 2 weeks to 3 months. Any deviation from
      this pattern is cause for concern and for a thorough evaluation of the
      breastfeeding process. Evaluation includes history taking and physical
      examination for the mother and infant. Observation of a breastfeeding session by
      a skilled clinician is crucial. A differential diagnosis is generated, followed
      by a problem-oriented management plan. Special techniques may be used to assist
      in complicated situations. Ongoing monitoring is required until weight gain has
      normalized. In most cases, early intervention can restore promptly infant growth
      and maternal milk supply. Underlying illness of the infant or mother must be
      considered if weight gain and milk supply do not respond to the earlier-mentioned
      interventions as expected. Physicians are responsible for knowledge about
      additional resources and for coordination of breastfeeding care. Pediatricians
      have a pivotal role in achieving the goals of optimal breastfeeding and
      appropriate infant growth.

PMID- 11339157
TI  - Prenatal, intrapartum, and postpartum support of the lactating mother.
AB  - Physicians must continue to improve their knowledge regarding lactation. Improved
      education will allow for alterations in standard practices that may deter
      breastfeeding. Presently known influences on successful breastfeeding should
      direct changes in clinic and hospital practices. Continued research into various
      aspects of care in and out of the hospital must be pursued to improve maternal
      infant care and breastfeeding.

PMID- 11339158
TI  - Hypoglycemia and the breastfed neonate.
AB  - Healthy, full-term infants are functionally and metabolically programmed to make
      the transition from their intrauterine dependent environment to their
      extrauterine existence without the need for metabolic monitoring or interference
      with the natural breastfeeding process. Full-term infants are equipped with
      homeostatic mechanisms that preserve adequate energy substrate to the brain and
      other vital organs. Thermal stability and early, properly guided, frequent,
      exclusive breastfeeding are the keys to success. Thus, routine screening for
      blood glucose concentrations or feeding sugar water is not necessary and
      potentially counterproductive to the establishment of a healthy mother-infant
      dyad.

PMID- 11339159
TI  - Jaundice and breastfeeding.
AB  - Optimal management of breastfeeding does not eliminate neonatal jaundice and
      elevated serum bilirubin concentrations. Rather, it leads to a pattern of
      hyperbilirubinemia that is normal and, possibly, beneficial to infants. Excessive
      frequency of exaggerated jaundice in a hospital or community population of
      breastfed infants may be a warning that breastfeeding policies and support are
      not ideal for the establishment of good breastfeeding practices. The challenge to
      clinicians is to differentiate normal patterns of jaundice and hyperbilirubinemia
      from those that indicate an abnormality or place an infant at risk.

PMID- 11339160
TI  - Iron and breastfeeding.
AB  - Given the importance of iron nutrition during the first year of life, there are
      surprisingly few true, randomized, controlled studies addressing this issue;
      however, it seems that iron deficiency is unlikely in full-term, breastfed
      infants during the first 6 months of life because these infants' body iron stores
      are sufficient to meet requirements. After this time, many infants exhaust their
      iron stores and become dependent on a secondary dietary iron supply. Although
      iron deficiency is a significant nutritional problem worldwide, most of the
      adverse effects of iron deficiency in this age group are hypothetical and rely on
      extrapolation from animal studies or studies at different ages. This, however,
      also is true of most of the adverse effects of iron excess in this age group.
      Given this uncertainty, it seems prudent to use the lowest dose of iron that
      prevents iron-deficiency anemia. Currently, the best evidence is that this is
      achieved by prolonged breastfeeding, avoidance of unfortified formulas and cow's
      milk, and the introduction of iron-fortified and vitamin C-fortified weaning
      foods at approximately 6 months of age. Despite much research, there are many
      areas of uncertainty regarding iron supplementation of infants, including that:
      1. The optimal age for introducing iron-fortified supplemental foods is poorly
      defined and should be further evaluated. 2. The natural history of iron
      deficiency and iron-deficiency anemia during the first year of life is unclear,
      as are the possible long-term effects of this, especially on developmental
      outcome. 3. The biologic variability among infants and among their mothers that
      allows many infants who do not receive iron-fortified foods to prevent iron
      deficiency while receiving only human milk throughout the first year of life is
      intriguing and warrants additional study. 4. The iron requirements of small-for
      gestational-age, term infants are unknown. Their iron requirements are likely to
      be higher than those of average term infants, but whether iron supplements are
      required is unclear. 5. The optimum amount of dietary iron in the weaning diet
      needs to be further defined. Similarly, the optimal source and amount of iron in
      infant formulas given to infants who receive a mixture of human milk and formula
      is unclear.

PMID- 11339161
TI  - Do breastfed infants need supplemental vitamins?
AB  - Table 2 shows that human milk will not meet the DRI for all vitamins in
      breastfeeding infants. The most glaring discrepancy between intake and the RDA is
      for vitamin D, although, as discussed, infants may synthesize this from sunlight
      exposure. Vitamin K must be given in the newborn period. Deficiencies of other
      vitamins are rare, especially if mothers are nourished adequately. If
      breastfeeding infants are to be supplemented with vitamin D or any other
      vitamins, the standard liquid preparations available all contain large amounts of
      the water-soluble and fat-soluble vitamins (except for vitamin K), which more
      than meets the RDA. The milk content of thiamin, pyridoxine, and niacin is
      correlated highly with maternal intake, and these vitamins are all present in
      relatively large amounts in standard multivitamin tablets given to lactating
      mothers. In conclusion, in healthy, breastfed infants of well-nourished mothers,
      there is little risk for vitamin deficiencies and the need for vitamin
      supplementation is rare. The exceptions to this are a need for vitamin K in the
      immediate newborn period and vitamin D in breastfed infants with dark skin or
      inadequate sunlight exposure.

PMID- 11339162
TI  - Breastfeeding in the special care nursery. Prematures and infants with medical
      problems.
AB  - In summary, clinical interventions that are focused on increasing the rates with
      which mothers initiate and sustain lactation for infants with medical problems
      must reflect the scientific evidence for this vulnerable population. These
      interventions should include counseling to ensure that mothers may make an
      informed decision about providing milk; nonpharmacologic and pharmacologic
      strategies to maximize maternal milk volume; and basing protocols for at-breast
      feeding on studies conducted with breastfeeding for premature and other at-risk
      infants, rather than on ideology or research conducted with term, healthy
      infants.

PMID- 11339163
TI  - Kangaroo mother care in the nursery.
AB  - Kangaroo mother care is becoming an integral part of the care of low birth weight
      infants worldwide. It provides economic savings to families and health care
      facilities and many physiologic and psychobehavioral benefits to mothers and
      infants, the most important of which is the promotion of successful
      breastfeeding. The benefits of breastfeeding, of human milk over formula, and of
      feeding from the breast per se, are beyond dispute, and so KMC should be actively
      promoted. The full impact of KMC on breastfeeding low birth weight infants is yet
      to be realized.

PMID- 11339164
TI  - Nutritional follow-up of the breastfeeding premature infant after hospital
      discharge.
AB  - In summary, fortification of human milk may be beneficial in preterm infants,
      particularly those born at less than 34 weeks' gestation or less than 1800 g
      birth weight, during and after initial hospitalization. This fortification after
      hospital discharge is more crucial for infants who cannot consume ad libitum
      quantities of breast milk, have poor growth, or have abnormalities in the
      biochemical screen of nutritional status. Although data indicate that in
      hospital, short-term gains in growth and mineral status are achieved, information
      is fragmentary regarding the influence on long-term growth and neurodevelopmental
      outcomes of feeding supplemented human milk. Also, no data are available on
      outcomes when providing these mixtures to premature infants after hospital
      discharge. It is recommended that a nutritional survey be accomplished before and
      approximately 1 month after discharge and that fortification or supplementation
      be initiated if an infant is failing to achieve normal growth and biochemical
      measures of nutrition.

PMID- 11339165
TI  - Breastfeeding in the workplace.
AB  - More than 50% of women of reproductive age are employed, and most return to work
      post partum at a time when exclusive breastfeeding is the ideal. Public health
      efforts target a goal of increased breastfeeding initiation and duration rates.
      To be successful at integrating the roles of breastfeeding mother and employee,
      women need practical advice, the encouragement and support of health care
      providers, and societal and workplace support. This article discusses the current
      state of employed breastfeeding women and provides practical guidelines for
      assisting women to be successful at meeting breastfeeding goals.

PMID- 11339166
TI  - Baby-Friendly Hospital Initiative. Protecting, promoting, and supporting
      breastfeeding in the twenty-first century.
AB  - The BFHI is a global UNICEF/WHO-sponsored effort to promote breastfeeding by
      ensuring that all women are provided with sound information regarding their
      infant feeding choices and that those who elect to breastfeed their infants are
      given physiologically sound, evidence-based advice and skilled assistance
      prenatally and as they begin nursing their infants during their postpartum
      hospital or birth center stay. The initiative is based on ten policy or procedure
      statements, The Ten Steps, which were jointly developed and published in 1989 by
      the sponsoring agencies in consultation with international experts. In 1990, the
      Ten Steps were accepted as the central theme of the Innocenti Declaration and,
      later that year, endorsed at the World Summit on Children. In 1992, UNICEF and
      WHO launched a major international campaign to encourage all hospitals with
      maternity services to accept the Ten Steps as basic maternity and newborn infant
      care policies and procedures. These Ten Steps were reviewed briefly in this
      article. Official designation as Baby Friendly requires a careful assessment
      completed by a trained external team to confirm that the institution is truly
      carrying out all Ten Steps and conforming to the International Code of Marketing
      of Breastmilk Substitutes. During the 8 years since the initiative began, more
      than 15,000 hospitals in 136 countries have been designated as Baby Friendly.
      Twenty-seven of these officially designated institutions are in the United
      States, where the campaign has been active only since 1996. The BFHI is
      considered one of the most successful international efforts ever performed to
      protect, promote, and support breastfeeding. Although it does not ensure that
      mothers will aspire to or achieve the widely accepted goal of approximately 6
      months of exclusive breastfeeding, it helps mothers to initiate exclusive
      nursing, an essential step in the right direction.

PMID- 11339167
TI  - Xenobiotics and breastfeeding.
AB  - Breastfeeding provides important benefits to mothers and infants and should be
      encouraged strongly as the optimal feeding choice for most infants. In assessing
      the effects of maternal medication on breastfeeding, clinicians must weigh the
      many benefits of breastfeeding for mothers and infants against the risk for
      exposing infants to a drug as it is present in breast milk. With regard to most
      medications, continued breastfeeding despite drug exposure is advantageous to
      mothers and infants.

PMID- 11339168
TI  - High-technology breastfeeding.
AB  - When there is interference with the natural process of breastfeeding,
      breastfeeding technology may be useful in supporting women to initiate and
      continue breastfeeding. Each breastfeeding mother has different technologic
      needs. By providing a range of choices and referrals, primary health care
      providers may facilitate the optimal decision for each lactating mother, which
      contributes to reaching the goals of the American Academy of Pediatrics for
      optimal infant feeding, that is, exclusive breastfeeding for the first 6 months
      of an infant's life, with continued breastfeeding for 1 year or more.

PMID- 11339169
TI  - The role of lactation specialists. A guide for physicians.
AB  - Breastfeeding support is a team event. The physician works with many health care
      professionals to provide complete care to the perinatal patient, including
      working with nurses trained in prenatal care, labor, delivery, and postpartum and
      newborn care, and working with midwives who provide prenatal care, labor, and
      delivery for the normal, uncomplicated patient. The pediatrician is part of this
      team and interacts with all of these players and with the office or clinic staff
      who provide follow-up, newborn, and child care.

PMID- 11339170
TI  - Every call is an opportunity. Supporting breastfeeding mothers over the
      telephone.
AB  - Breastfeeding generates numerous questions. Every call about breastfeeding
      received over the telephone is an opportunity for health care professionals to
      listen and support the caller and offer factual information and advice to help
      the family to have an enjoyable breastfeeding experience.

PMID- 11339171
TI  - Ten steps to support parents' choice to breastfeed their baby. American Academy
      of Pediatrics Work Group on Breastfeeding.

PMID- 11339172
TI  - Resources for physicians. Web sites, books, and organizations.

PMID- 11339174
TI  - [Maternity desire in patients undergoing assisted reproduction treatment at a
      public health institution].
AB  - The main purpose of this investigation was to define how different psychic
      representations of the desire for maternity have determined the decision of a
      group of patients to be under complicated reproductive treatments such as in
      vitro fertilization. A hundred patients who wanted to be under Assisted Human
      Reproduction (AHR) treatments in a public health institution were interviewed.
      Ten of them were selected to be studied in depth. The methodology employed was
      interpretative on a grounded theory design. Although this analysis included many
      factors, such as gender, family pressures, medical institution and side effects
      of this treatment, the two constant predominanting factors were narcisistic
      personality and the imaginary child.

PMID- 11339175
TI  - [Medical liability in gynecology and obstetrics. Analysis of 25 cases].
AB  - The authors studied 175 severe medical complaints which ended in Arbitration
      veredicts or expert opinions, handled by and Alternative Disputes Resolution
      Institution (CONAMED) between June 1996 and December 1999. The study was focused
      on 25 cases with complete medical records. Belonged to Gynecology area, 8 cases
      (32%), and 17 cases (68%) to Obstetrics. The physicians involved were ob/gyn
      specialists in 14 cases. Health public institutions were involved in 14 cases
      (56%), and private practitioners, 11 cases (44%). The main sources of
      unsatisfaction were injuries or technical failures during surgical procedures in
      24% (6 cases) or diagnostic failures in 6 cases (24%). The outcomes were: deaths
      8 (32%), amputation or another sequelae in three cases (12%), and fetus or
      newborns deaths or injuries in two cases (6%). The claimers asked for monetary
      benefits in 15 cases (60%), disclosure of medical responsibility in 8 cases
      (24%), and to probe murder or injuries in 3 cases (12%). The CONAMED conclusions
      were medical malpractice in 14 cases (56%), administrative failures in 14 cases
      (56%), and patient responsibility in 4 cases (16%).

PMID- 11339176
TI  - [Prognostic value assessment of the early response of blood estradiol, FSH, and
      LH using leuprolide acetate during ovarian hyperstimulation in assisted
      reproduction].
AB  - OBJECTIVE: Evaluate the prognostic value of the early response of the serum
      estradiol FSH y LH action of leuprolide acetate during the folicular phase, used
      as an adjuvant to ovarian stimulation in IVF-ET. STUDY DESIGN: Were analyzed 31
      cycles of stimulation in 26 patients with sterility primary and secondary. Where
      measured estradiol, FSH, LH on cycle day 2 to 5 for to establish the patterns of
      response to GnRHa administration. Were compared the response patterns in relation
      to the number of oocyte captured, estradiol in the day of application of hCG,
      number of embryos and fertilization rate using (t-student, wilcoxon test and X2).
      RESULTS: Where observed four distincts patterns of response of estradiol. Pattern
      A: 133 cycles, presented a prompt elevation of estradiol, followed by a fall on
      the 4th cycle's day. Pattern B: 9 cycles delayed elevation of the estradiol,
      followed by a fall on the 6th cycles day. Pattern C: 7 cycles showed persistent
      elevation of the estradiol. Pattern D: 2 cycles no response of the estradiol
      (canceled cycles). Was found a significative difference in the estradiol level
      the day of application of hCG, number of captured oocytes and number of embrions
      in the pattern A in relation with B and C. No significative difference were found
      in the fertilization rate. The seric level of FSH and LH were no predictives. We
      concluded that the response pattern of the estradiol to the leuprolide acetate is
      the good prognosis indicator of the results of IVF-ET.

PMID- 11339177
TI  - [Bilateral ovary massive edema. Unusual gynecologic pathology. Report of 2
      cases].
AB  - We report two cases of bilateral massive ovarian edema occurred in a
      concentration hospital in the last five years. This condition was first described
      by Kalstone et al. in 1969. It may be uni or bilateral, the last one is very
      uncommon, until the moment of this work there have been reported only ten cases
      in the world literature. The main symptoms are: abdominal pain or distention,
      menstrual irregularity and infertility. Two features are characteristic of this
      pathology: 1) Fast growing in size and volume of the ovary, and 2) Abscense of
      neoplastic changes with extensive edema of the stroma particularly in the
      medulla. The current treatment is oophorectomy. In bilateral cases may be
      intended a conservative management with wedge resection and fixation of the
      ovaries to the uterus in order to prevent further torsion. We conclude that
      massive ovarian edema is an uncommon pathology more frequent as a cause of
      abdominal pain and fast growing anexial mass in young women.

PMID- 11339178
TI  - [Physiological significance of zinc: perinatal approximation].
AB  - Zinc is a very important micronutrient in several biological functions. During
      pregnancy, zinc deficiency causes fetal-growth retardation, malformations and
      others poor pregnancy outcomes. The additional need for zinc during pregnancy can
      be met by an increase in zinc intake, bioavailability or by physiologic
      adjustments in zinc homeostasis. However, there are factors associated with low
      intestinal zinc absorption such as diets high in phytate, and iron or calcium
      supplementation. Further studies of maternal zinc status are necessary to define
      a prophylactic supplementation to prevent zinc deficiency during pregnancy.

PMID- 11339179
TI  - [Minimally deviated adenocarcinoma (malignant adenoma) of the cervix uteri].
AB  - Minimal deviation adenocarcinoma (adenoma malignum) is a rare well-differentiated
      form of invasive cervical adenocarcinoma. Because of its rarity and cytologic
      changes are subtle there are only a few reports of this pathology, been necessary
      the realization of large biopsy of the cervical tissue for it histological
      diagnosis. We made a review in the period 1994-2000, of the clinical,
      cytological, histological features, treatments and follow-up of 4 patients in the
      Gynecologic Oncology Department of the University Hospital Vall d' Hebron,
      Barcelona, Spain.

PMID- 11339180
TI  - [Evans syndrome, pregnancy, and preeclampsia].
AB  - Evans' syndrome is an unusual illness of autoimmune etiology, characterized by
      thrombocytopenia and hemolytic anemia. This is more frequent in females
      throughout first half of the life and during pregnancy. The present paper
      describes two pregnant women with Evans syndrome associated to preeclampsia. This
      report emphasizes how the hematology and coagulation abnormalities of
      preeclampsia could be added to those abnormalities observed in Evans' syndrome.
      This association constitutes a severe disease of difficult treatment.

PMID- 11339181
TI  - Fetal echocardiography: state of the art of the state of the heart.

PMID- 11339182
TI  - Assessment of ductus venosus flow during the first and early second trimesters:
      what can we expect?

PMID- 11339183
TI  - Ductus venosus studies in fetuses at high risk for chromosomal or heart
      abnormalities: relationship with nuchal translucency measurement and fetal
      outcome.
AB  - OBJECTIVE: To investigate, in a high-risk group of fetuses, the role of ductus
      venosus Doppler velocimetry as a prognostic factor, in addition to nuchal
      translucency measurement, for predicting chromosomal anomalies and, where the
      karyotype was normal, for predicting fetal outcome. METHODS: Nuchal translucency
      was measured and ductus venosus pulsatility index and late diastolic flow (a
      wave) were recorded in 186 fetuses at a median gestational age of 12.6 weeks
      (range, 10-17). Fetal karyotype, the presence of structural anomalies, pregnancy
      outcome, neonatal examination at birth and postnatal follow up were the outcome
      values. RESULTS: Nuchal translucency measurement was increased in 112 fetuses.
      The outcome of pregnancy was normal in 130 fetuses. Fifty-six fetuses had an
      adverse outcome (46 chromosomal anomalies, three intrauterine deaths, six
      structural anomalies and one developmental disorder). The sensitivity of an
      abnormal ductus venosus pulsatility index or of absent or reversed flow during
      the a-wave was 65% for chromosomal anomalies and 68% for an adverse outcome. The
      specificity was 79%. There was a significant correlation between nuchal
      translucency and ductus venosus pulsatility index. In chromosomally normal
      fetuses with an enlarged nuchal translucency an abnormal ductus venosus flow was
      associated with a nearly nine-fold increase in adverse outcome (odds ratio 11.7).
      CONCLUSION: Ductus venosus Doppler velocimetry can be used in addition to nuchal
      translucency measurement as a predictor of chromosomal anomalies. However, as the
      ductus venosus blood flow pattern is correlated with nuchal translucency
      measurement it cannot be used as an independent variable to reduce the indication
      for fetal karyotyping. Ductus venosus Doppler velocimetry may have a role in the
      counseling of parents in the case of an enlarged nuchal translucency and normal
      karyotype by identifying those fetuses in need of an intensive follow up due to
      an increased risk of adverse outcome.

PMID- 11339184
TI  - The role of ductus venosus blood flow assessment in screening for chromosomal
      abnormalities at 10-16 weeks of gestation.
AB  - OBJECTIVE: To evaluate the role of ductus venosus blood flow assessment at 10-16
      weeks' gestation in screening for chromosomal abnormalities. METHODS: Ductus
      venosus blood flow was prospectively evaluated in 1371 consecutive pregnancies
      between 10 and 16 weeks of gestation. The pulsatility index for veins was
      calculated. All cases were screened for chromosomal defects combining maternal
      age and fetal nuchal translucency thickness. RESULTS: A chromosomal abnormality
      was found in 20 cases. The overall detection rate, specificity, positive
      predictive value, negative predictive value and odds ratio for chromosomal
      abnormalities were 65%, 95.7%, 18.3%, 99.5% and 41 (95% CI 16-108), respectively,
      when using the 95th centile pulsatility index as a cut-off. CONCLUSIONS: These
      preliminary results suggest that evaluation of the ductus venosus pulsatility
      index at 10-16 weeks' gestation is a useful second-line screening test for
      chromosomal defects. A combination of nuchal translucency measurement and ductus
      venosus assessment might increase specificity while maintaining an optimal
      detection rate for chromosomal abnormalities. Such a policy could identify 55% of
      all chromosomal abnormalities and about 69% of autosomal trisomies, reducing the
      need for invasive testing to less than 1%.

PMID- 11339185
TI  - Reproducibility of ductus venosus Doppler flow measurements at 11-14 weeks of
      gestation.
AB  - OBJECTIVES: To assess the intra- and interobserver repeatabilities of fetal
      ductus venosus Doppler measurements at 11-14 weeks of gestation. DESIGN: Flow
      velocity waveforms were recorded transabdominally. Intraobserver repeatability
      was studied in 22 fetuses in whom four repeated measurements were performed by
      the same observer. Interobserver repeatability was assessed in 54 fetuses in each
      of whom two observers performed two repeated measurements. The pulsatility index
      for veins (PIV), peak velocity during ventricular systole (S wave), peak velocity
      during atrial contraction (A wave) and time-averaged maximum velocity (TAMV) were
      recorded. Reproducibility of the Doppler measurements was analyzed by calculating
      repeatability coefficient, coefficient of variation (CV), intraclass correlation
      coefficient (ICC), mean differences and their limits of agreement. Cohen's k
      coefficient was used for categorical data. RESULTS: Intraobserver repeatability
      was good with a CV of 10%, 13%, 22% and 13% and an ICC of 0.85, 0.94, 0.94 and
      0.95, respectively, for PIV, S wave, A wave and TAMV. Interobserver repeatability
      was also good, and no bias between the observers was detected. A CV of 8.8%, 14%,
      27% and 15% and an ICC of 0.86, 0.84, 0.87 and 0.84, respectively, for PIV, S
      wave, A wave and TAMV were obtained. There was 100% agreement for the detection
      of normal/abnormal blood flow. CONCLUSIONS: Intra- and interobserver
      repeatability of all parameters was acceptable, allowing for the detection of
      moderate to large changes in Doppler measurements.

PMID- 11339186
TI  - Intraobserver and interobserver variability of transabdominal Doppler velocimetry
      measurements of the fetal ductus venosus between 10 and 14 weeks of gestation.
AB  - OBJECTIVE: To assess the intraobserver repeatability and interobserver
      reproducibility of transabdominal Doppler ultrasound measurements of ductus
      venosus blood flow in fetuses between 10 and 14 weeks of gestation. DESIGN: A
      prospective study with the following end-points: coefficient of variation,
      intraclass correlation coefficients within and between observers, repeatability
      coefficient and Cohen's kappa coefficient. SUBJECTS AND METHODS: Doppler
      velocimetry indices (maximum peak systolic velocity during ventricular systole,
      end-diastolic velocity during atrial contraction, peak systolic velocity/end
      diastolic velocity ratio and pulsatility index for veins) were successfully
      measured three times by the same trained observer in 67 fetuses. Of these, in 24
      fetuses, the measurements were then repeated by a second trained observer. In
      addition, both observers classified qualitatively the blood flow as being normal
      or abnormal with regard to the presence or absence/reversal of flow during atrial
      contraction. RESULTS: The intraobserver repeatability of the pulsatility index
      for veins measurements was considered good with a coefficient of variation of
      8.9% and an intraclass correlation coefficient value of 0.62. However,
      inconsistencies occurred in maximum peak systolic velocity, end-diastolic
      velocity and systolic/diastolic ratio measurements, which had coefficients of
      variation of 19%, 28.5%, and 25.4%, respectively. The corresponding intraclass
      correlation coefficient values were 0.70, 0.69 and 0.60. Interobserver
      reproducibility of these indices was unsatisfactory, the coefficient of variation
      varying between 11.5% and 47.2% and the intraclass correlation coefficient
      between 0.18 and 0.44. Agreement between the repeated observations with regard to
      interpretation of normal or abnormal blood flow varied from moderate
      (interobserver) to very good (intraobserver). CONCLUSIONS: There was considerable
      variability in all Doppler indices except for the intraobserver repeatability of
      the pulsatility index for veins measurement. This makes the implementation of the
      semiquantitative Doppler indices in a screening setting difficult. On the
      contrary, qualitative classification of the flow velocity waveforms seemed to be
      a reproducible method.

PMID- 11339187
TI  - Fetal cardiac performance in uncomplicated and well-controlled maternal type I
      diabetes.
AB  - OBJECTIVE: To study the impact of well-controlled, uncomplicated maternal
      diabetes on fetal cardiac development and performance. METHODS: The following
      variables were studied in 45 fetuses of type I diabetic women by means of mid-
      and late-trimester echocardiography: interventricular septal thickness; aortic
      and pulmonary valve diameters; peak and time-to-peak flow velocity of the great
      arteries; the ratio between peak velocities during early (E) and late (A)
      ventricular filling at the level of the atrioventricular values; ventricular
      fractional shortenings; and output. The findings were compared to age-matched
      control groups of normal fetuses. RESULTS: A significant augmentation of
      interventricular septal thickness was demonstrated for mid-trimester fetuses of
      diabetic women, which progressed further towards the end of pregnancy. However,
      the indices of diastolic and systolic function remained comparable between the
      gestational age-matched groups. CONCLUSION: Progressive myocardial thickening
      occurs commonly in mid- and late-trimester fetuses of uncomplicated and well
      controlled diabetic pregnancies. The observed degree of hypertrophy is generally
      mild and does not affect age-related changes in fetal cardiac function.

PMID- 11339188
TI  - Power spectrum analysis of heart rate and blood flow velocity variability
      measured in the umbilical and uterine arteries in early pregnancy: a comparative
      study.
AB  - OBJECTIVE: To compare power spectral derived variability parameters from the
      fetal side of the placental circulation with those from the maternal side of the
      placental circulation, during early pregnancy. METHODS: Doppler velocity
      waveforms were obtained from both the umbilical and the uterine arteries in a
      study group of 40 pregnant women between 10 and 14 (n = 25) and 15 and 20 (n =
      15) weeks of gestation. The coefficient of variation of both the beat-to-beat
      heart rate variability and the blood flow velocity variability was determined.
      The ratio of the integrated low-frequency components (< 0.2 Hz) and the
      integrated high-frequency components (> 0.2 Hz) from normalized power spectrum
      analysis (LH-ratio) was established, to reflect sympathovagal balance. RESULTS:
      The coefficient of variation and LH-ratio of fetal heart rate variability
      constitute only a fraction of the same maternal heart rate variability
      parameters. Nevertheless a highly significant increase (P < 0.001) in LH-ratio
      was demonstrated with advancing gestational age. The coefficient of variation and
      LH-ratio of blood flow velocity variability were significantly lower in the fetal
      umbilical artery only in the 10-14-weeks' gestation group. Due to a decrease of
      the maternal uterine blood flow velocity variability parameters with advancing
      gestational age, statistically equal fetal and maternal values for coefficient of
      variation and LH-ratio were found in the 15-20 weeks' gestation group.
      CONCLUSIONS: The increase in LH-ratio of fetal heart rate variability indicates
      functional development of the fetal autonomic nervous system at 15-20 weeks'
      gestation. The umbilical blood flow velocity variability may be secondary to
      maternal uterine arterial flow variability rather than due to primary changes in
      fetal cardiovascular function.

PMID- 11339189
TI  - Prenatal diagnosis of thrombosis of the dural sinuses with real-time and color
      Doppler ultrasound.
AB  - OBJECTIVE: To assess the sonographic findings and clinical implications of fetal
      thrombosis of dural sinuses. DESIGN: Retrospective study of cases with a prenatal
      diagnosis of thrombosis of the dural sinuses. RESULTS: The diagnosis of fetal
      thrombosis of the dural sinuses was established in three uncomplicated
      pregnancies at 21, 22 and 28 weeks' gestation by transabdominal and transvaginal
      sonography, demonstrating a blood clot within the dilated dural sinuses, always
      in the region of the torcular Herophilii. The diagnosis was further confirmed by
      the color Doppler demonstration of absence of blood flow within the dilated dural
      sinuses. Upon request of the couples two pregnancies were terminated. One infant
      was delivered at term by Cesarean section and died during neurosurgery.
      CONCLUSIONS: Thrombosis of the cerebral venous circulation can occur antenatally.
      Accurate diagnosis can be made using fetal real-time and color Doppler
      ultrasound.

PMID- 11339190
TI  - The variability in the interpretation of prenatal diagnostic ultrasound.
AB  - OBJECTIVES: Although prenatal ultrasound is broadly used to detect abnormal
      fetuses, the variability in the interpretation of second-trimester prenatal
      ultrasound examinations is unknown. We sought to evaluate the consistency of the
      interpretation of prenatal ultrasound examinations. DESIGN: Physicians who
      perform prenatal ultrasound and who participate in the California Maternal Serum
      Expanded AFP program were asked to interpret a series of test ultrasound
      examinations. The series of cases was selected to include a random sample of
      fetal structural abnormalities, ultrasound markers that have been associated with
      chromosomal abnormalities, and normal cases. Interobserver agreement was
      evaluated using a kappa statistic for each organ system. The sensitivity and
      false-positive rate were calculated for detecting specific anatomic abnormalities
      within each organ system. RESULTS: Of the 210 sonologists eligible for inclusion
      in the study, completed responses were received from 148 (70%). There was
      moderate to substantial agreement between physicians in reporting the presence of
      fetal abnormalities for all organ systems (kappa range 0.40-0.88, P < 0.001). The
      consistency was highest for the central nervous system (CNS), neck, and face.
      Within each organ system, the consistency was similar for major structural
      abnormalities and ultrasound markers of chromosomal abnormalities. The
      sensitivity ranged from 62% (95% confidence interval (CI) 58-66%) for major renal
      abnormalities to 91% (95% CI 88-94%) for CNS abnormalities, with corresponding
      false-positive rates of 7% (95% CI 6-9%) for renal abnormalities and 9% (95% CI 7
      11%) for CNS abnormalities. For most organ systems, the sensitivity for detecting
      ultrasound markers of chromosomal abnormalities was similar to the sensitivity
      for detecting structural abnormalities. CONCLUSION: There is moderate to
      substantial agreement in the interpretation of second-trimester prenatal
      ultrasound examinations. Whether the identification of specific ultrasound
      abnormalities and markers is overall beneficial to patients remains to be
      determined.

PMID- 11339191
TI  - Isolated hyperechogenic foci in the fetal thalamus in early pregnancy.
AB  - OBJECTIVE: To describe the sonographic features and outcome of fetuses with
      isolated hyperechogenic foci in the thalamic region. METHODS: A detailed
      sonographic survey was performed in 46,244 consecutive pregnancies. Both low- and
      high-risk pregnancies were included. Transvaginal examinations were performed at
      14-16 weeks' gestation, while transabdominal examinations were performed after 18
      weeks' gestation. RESULTS: Isolated hyperechogenic foci in the thalamic region
      were observed in seven fetuses. All cases were diagnosed at 14-16 weeks'
      gestation. Six fetuses had one hyperechogenic focus, and one fetus had two foci.
      The size of these foci ranged from 2-4 mm. A serologic work-up was negative in
      all these fetuses and their karyotype was normal. The hyperechogenic foci
      disappeared in mid-pregnancy in all cases, and fetuses were normal at delivery
      and on follow up to the age of 9 years. CONCLUSIONS: Isolated hyperechogenic foci
      in the thalamic region in early pregnancy are probably benign in nature.

PMID- 11339192
TI  - Cervical length at 22-24 weeks of gestation: comparison of transvaginal and
      transperineal-translabial ultrasonography.
AB  - OBJECTIVES: To investigate the feasibility of measuring cervical length by
      transperineal or translabial sonography and compare the measurements obtained by
      this approach with those obtained transvaginally. METHODS: In 500 women
      measurement of cervical length by translabial-transperineal sonography was
      attempted immediately before transvaginal scanning at 22-24 (median 23) weeks of
      gestation. In the first phase of the study, considered to be the learning period,
      200 patients were examined and their results reviewed, before carrying out the
      second phase in which 300 patients were examined. A comparison was made of the
      patient acceptability of both techniques. RESULTS: Cervical length was
      successfully measured transvaginally in all cases. In the first phase of the
      study cervical length was measured by translabial-transperineal sonography in 84%
      of the 200 patients but there was poor agreement with measurements obtained
      transvaginally and the 95% tolerance interval for paired observations was -11.0
      mm to 16.1 mm. After audit of results it became apparent that the translabially
      transperineally derived images were inadequate in more than half of the cases but
      in those with adequate paired measurements there was a very good agreement
      between the two and the 95% tolerance interval for paired observations was -5.8
      mm to 5.2 mm. In the second phase of the study special attention was paid towards
      recording measurements of cervical length only in cases where both the internal
      and external os were adequately visualized. Successful measurements by
      translabial-transperineal sonography were obtained in 78% of cases and the 95%
      tolerance interval for paired observations was -5.8 mm to 6.1 mm. The degree of
      patient acceptability of the two methods was similar. CONCLUSIONS: The findings
      of this study suggest that at 22-24 weeks of gestation the cervix can be
      visualized adequately by translabial-transperineal sonography in about 80% of
      patients and the measurements of cervical length obtained by this approach are
      very similar to those obtained by transvaginal sonography.

PMID- 11339193
TI  - Prenatal diagnosis of mosaic trisomy 8 in a fetus with normal nuchal translucency
      thickness and reversed end-diastolic ductus venosus flow.
AB  - We report a case of the prenatal diagnosis of trisomy 8 in a fetus presenting
      with normal nuchal translucency of 0.8 mm and reversed end-diastolic ductus
      venosus blood flow at a routine first-trimester scan at 11 weeks of gestation. No
      structural abnormalities were detected by the ultrasound scan. Karyotyping by
      chorionic villus sampling led to the diagnosis of mosaic trisomy 8, which was
      confirmed by fluorescent in-situ hybridization on fetal tissue samples.

PMID- 11339194
TI  - First-trimester increased nuchal translucency and fetal hypokinesia associated
      with Zellweger syndrome.
AB  - We report the prenatal detection of increased nuchal translucency and decreased
      fetal movements, at 11 weeks of gestation, in a fetus at risk for Zellweger
      syndrome. The diagnosis of Zellweger syndrome was confirmed by metabolic studies
      on cultured chorionic villus sampling (CVS) cells and the pregnancy was
      terminated. The couple's subsequent pregnancy was monitored using the same
      method. In this pregnancy the nuchal translucency measured at 12 weeks' gestation
      was normal, the fetus was active, and biochemical studies using CVS and
      amniocentesis confirmed normal results. We believe this to be the first reported
      case of Zellweger syndrome followed prenatally in which an increased nuchal
      translucency and fetal hypokinesia were detected in the first trimester. During
      the pregnancy with the affected child the maternal serum screen (MSS) showed low
      estriol level. We believe this to be the second report of a low estriol level on
      MSS in a pregnancy affected with Zellweger syndrome.

PMID- 11339195
TI  - Prenatal diagnosis and outcome of a ruptured aneurysm arising from the left
      atrium.
AB  - Prenatal diagnosis of a fetal cardiac aneurysm or diverticula is rare. We report
      what we believe to be the first case of an atrial wall aneurysm diagnosed as
      ruptured or leaking by fetal pericardiocentesis. Spontaneous resolution of the
      anomaly was observed in the third trimester with delivery of a vigorous newborn
      at term. The infant did not require surgical intervention after birth and has
      done well at follow-up examinations.

PMID- 11339196
TI  - Serial sonographic findings in a fetus with congenital hiatal hernia.
AB  - A continuum of prenatal findings in a case of hiatal hernia is described. Second
      trimester scans showed absence of fetal stomach and polyhydramnios suggestive of
      esophageal atresia. Third-trimester scans revealed a dilated tubular structure in
      the thoracic cavity with intermittent visualization of an intra-abdominal small
      stomach. A diagnosis of hiatal hernia was entertained. After birth, the diagnosis
      of a dilated esophagus with the stomach herniated into the thoracic cavity
      through a very lax esophageal hiatus was confirmed and the baby underwent
      corrective surgery.

PMID- 11339197
TI  - Prenatal diagnosis of Bardet-Biedl syndrome by targeted second-trimester
      sonography.
AB  - Bardet-Biedl syndrome (BBS) is an autosomal recessive disorder characterized by
      mental retardation, obesity, retinal degeneration, polydactyly and syndactyly,
      diabetes mellitus, hypogenitalism, renal dysplasia and short stature. Definitive
      molecular diagnosis for BBS is not currently available and counseling of affected
      families is based on the 25% recurrence risk consistent with autosomal recessive
      inheritance. Our case presents the first successful use of second trimester
      targeted sonographic anatomy scanning to prospectively identify a fetus affected
      with BBS, and indicates that ultrasound can be of critical importance in
      providing precise as well as timely prenatal diagnosis for families at risk for
      this serious disorder.

PMID- 11339198
TI  - The dilemma of prenatal diagnosis of bladder exstrophy: a case report and a
      review of the literature.
AB  - Bladder exstrophy is a very rare congenital anomaly characterized by the
      exteriorization of the viscera on the abdominal surface, low insertion of the
      umbilical cord, divergent pubic rami and abnormal exterior genitalia. We report a
      case of prenatal diagnosis of fetal bladder exstrophy in which the urachus
      resembled the normal bladder. Considering that non-visualization of the bladder
      is one of the main findings in cases of bladder exstrophy, special attention
      should be given to fetal lower abdominal cystic images in order to differentiate
      them from a normally positioned fetal bladder. A review of the literature
      together with a sonographic study of the urachus is provided.

PMID- 11339199
TI  - First-trimester sonographic demonstration of a mobile cranial cyst associated
      with anencephaly and amniotic band sequence.

PMID- 11339200
TI  - Sonographic appearance of tornado blood flow in placenta previa accreta/increta.

PMID- 11339201
TI  - [Consciousness, cognition and animal welfare].

PMID- 11339204
TI  - Staphylococcal septicaemia in burns.

PMID- 11339205
TI  - Costing vaccines versus bednets.

PMID- 11339206
TI  - Human immune response to Trichuris trichiura.

PMID- 11339207
TI  - Who gives an iota about DNA repair?

PMID- 11339208
TI  - Organelle genome resource at NCBI.

PMID- 11339210
TI  - Renal microvascular effects of P2 receptor stimulation.
AB  - 1. The field of extracellular nucleotides and purinoceptors has undergone a
      resurgence of interest and enthusiasm in the past decade. More and more
      investigators are probing the physiological and pathophysiological roles of P2
      receptors in virtually every organ system, including the kidney. 2. With this
      renewed interest has come a new appreciation for the roles extracellular adenine
      nucleotides can play in regulating or modulating renal function. In the past 5
      years, investigators have provided compelling evidence that extracellular
      nucleotides, working through activation of P2 purinoceptors, have a significant
      impact on renal microvascular function, mesangial cell function and on renal
      epithelial transport. 3. Evidence has been uncovered that implicates P2 receptor
      activation in mediating renal microvascular autoregulatory behaviour. Locally
      released ATP has a direct paracrine and/or autocrine effect modulating renal
      epithelial transporters and tubular epithelial channels to influence tubular
      fluid composition. 4. While the specific roles of extracellular nucleotides and
      their receptors in the kidney have not been absolutely identified, it now appears
      clear that endogenously released ATP may play a significant role in regulating
      kidney function. 5. The purpose of the present review is to update our current
      understanding of the effect of P2 receptor activation on renal microvascular
      function and to detail the signal transduction mechanisms known to be involved.

PMID- 11339211
TI  - ATP release mechanisms, ATP receptors and purinergic signalling along the
      nephron.
AB  - 1. Autocrine and paracrine signalling along the nephron of the kidney has been a
      widely held hypothesis for several decades. The lumen of the nephron is an ideal
      autocrine and paracrine signalling microenvironment. Any agonist, filtered at the
      glomerulus or released in the proximal tubule or other proximal segments, is
      subsequently trapped in the lumen of the nephron and present to interact with
      luminal receptors. Similar signalling in the renal interstitium is also possible
      and likely. Indeed, receptors for many autocrine and paracrine agonists have been
      characterized on the luminal membrane and serosal membrane of multiple nephron
      segments. 2. An important family of autocrine and paracrine agonists in the
      kidney are the purinergic agonists. Extracellular ATP, as well as its metabolites
      (ADP, 5'-AMP and adenosine), is released by renal epithelial cells. These
      compounds are also freely filtered at the glomerulus and are found in the final
      urine. Receptors for ATP and adenosine are also expressed on the luminal and
      serosal side of many nephron segments. 3. The present review discusses purinergic
      signalling by nucleotide agonists in an integrated manner, from ATP release to
      ATP receptors to extracellular ATP-mediated effects on renal epithelial function.
      These themes are the focus of our laboratory in normal and polycystic kidneys as
      well as in normal and diseased epithelial cells from other tissues. The
      physiological roles of extracellular purinergic signalling in the kidney and
      other tissues are only beginning to emerge.

PMID- 11339212
TI  - P2Y receptors of MDCK cells: epithelial cell regulation by extracellular
      nucleotides.
AB  - 1. Madin-Darby canine kidney (MDCK) cells, a well- differentiated renal
      epithelial cell line derived from distal tubule/collecting duct, respond to
      extracellular nucleotides by altering ion flux and the production of arachidonic
      acid-derived products, in particular prostaglandin E2 (PGE2). Our work has
      defined the receptors and signalling events involved in such responses. 2. We
      have found evidence for expression of at least three P2Y receptor subtypes (P2Y1,
      P2Y2 and P2Y11) in MDCK-D1 cells, a subclone from parental MDCK. 3. These
      receptors appear to couple to increases in calcium and protein kinase C activity,
      probably via a Gq/G11-mediated activation of phospholipase C. 4. In addition, P2Y
      receptor activation can promote a prominent increase in cAMP. This includes both
      a P2Y2 receptor-mediated cyclo-oxygenase (COX)-dependent component and another
      COX-independent component mediated by other P2Y receptors. 5. We have documented
      that changing media in which cells are grown releases ATP and, in turn, activates
      P2Y receptors. Such release of ATP contributes in a major way to basal cAMP
      levels in these cells. 6. The data indicate that MDCK cells are a useful model to
      define the regulation of epithelial cells by extracellular nucleotides. Of
      particular note, spontaneous or stretch-induced release of ATP and subsequent
      activation of one or more P2Y receptors contributes to establishing the basal
      activity of signalling pathways.

PMID- 11339213
TI  - Mediterranean diet revisited.

PMID- 11339214
TI  - Mediterranean diet revisited.

PMID- 11339215
TI  - Mediterranean diet revisited.

PMID- 11339216
TI  - Recent developments in the combinatorial synthesis of nitrogen heterocycles using
      solid phase technology.
AB  - Recognizing the potential of combinatorial chemistry to accelerate drug discovery
      and development, most pharmaceutical and related industries are seriously looking
      toward combinatorial synthesis of compounds in order to facilitate the
      identification of 'lead' molecules. In particular, solid phase synthesis is the
      core technology for combinatorial chemistry and is widely used for generating
      libraries of structurally related compounds. Since many drugs contain the
      nitrogen heterocyclic component and since heterocycles possess a high order of
      structural diversity, a precise overview of recent progress in the combinatorial
      synthesis of nitrogen heterocycles using solid phase methodology would be useful.
      Since the progress in solid phase synthesis of organic molecules has been
      reviewed regularly from 1992 to 1998, only the development of solid phase
      combinatorial synthetic approaches of small nitrogen heterocycles since 1999 will
      be reviewed here. This review describes the solid phase synthesis of azepanes,
      benzodiazepines, benzimidazoles, benzothiazepines, cinnolines, indolizines, beta
      lactams, oxazepins, oxazoles including benzisooxazoles, hydantoins, piperidines,
      pyrimidines, pyrazolones, quinolones, trizolopyridazines and thiazoles.

PMID- 11339217
TI  - Genetics and molecular biology.

PMID- 11339218
TI  - Blue colon at autopsy.

PMID- 11339219
TI  - Tumors and hypomelanosis of Ito.

PMID- 11339220
TI  - Be careful what you wish for.

PMID- 11339221
TI  - Strengthening governance for global health research. Ways of getting vitamin A to
      children in developing countries have to be improved.

PMID- 11339222
TI  - Ranitidine and gastrointestinal bleeding in intensive care. Should prophylaxis
      against stress ulcer be abondoned for patients in intensive care.

PMID- 11339223
TI  - Ranitidine and gastrointestinal bleeding in intensive care. Occult blood loss is
      clinically important.

PMID- 11339224
TI  - Glycated haemoglobin, diabetes, and mortality in men. Analytical information is
      required for generalisation of data.

PMID- 11339225
TI  - Glycated haemoglobin, diabetes, and mortality in men. Maybe disturbance in
      physiological mechanisms regulating blood glucose is risk factor for
      cardiovascular death.

PMID- 11339226
TI  - Glycated haemoglobin, diabetes, and mortality in men. Medicine is now using
      diagnostic criteria rather than reference ranges.

PMID- 11339227
TI  - Catheterisation in elderly women is no "easy" option.

PMID- 11339228
TI  - Weekend binge drinking may be linked to Monday peaks in cardiovascular deaths.

PMID- 11339229
TI  - Fillers can transform people's lives.

PMID- 11339230
TI  - Invalid health information is potentially lethal.

PMID- 11339231
TI  - Metabolism of 2-nitrofluorene, 2-aminofluorene and 2-acylaminofluorenes in rat
      and dog and the role of intestinal bacteria.
AB  - 1. The in vivo metabolism of 2-nitrofluorene (NF), an environmental pollutant,
      and 2-aminofluorene (AF) and its acylated derivatives, 2-formylaminofluorene
      (FAF) and 2-acetylaminofluorene (AAF), was examined in rat and dog. 2. 7-Hydroxy
      2-nitrofluorene, 5-hydroxy-2-nitrofluorene, AF, AAF, FAF, 7-hydroxy-2
      aminofluorene, 5-hydroxy-2-aminofluorene, 7-hydroxy-2-acetylaminofluorene, 5
      hydroxy-2-acetylaminofluorene, 7-hydroxy-2-formylaminofluorene and 5-hydroxy-2
      formylaminofluorene were identified as urinary and faecal metabolites of NF in
      rat and dog. 3. AAF and its hydroxylated derivatives were detected as major
      metabolites of NF in rat, but FAF and its hydroxylated metabolites were mainly
      excreted in dog. 4. AF, AAF, FAF and their hydroxylated metabolites were also
      identified as urinary and faecal metabolites of AF, AAF or FAF in rat, suggesting
      that AAF and FAF are interconverted via AF. 5. Treatment of rat and dog with
      antibiotics significantly decreased the urinary and faecal excretion of AF and
      its derivatives after oral administration of NF, and partly decreased the
      excretion of acylated metabolites after an oral dose of AF. 6. The caecal
      contents of untreated rats and some species of intestinal bacteria exhibited
      nitro-reductase activity toward NF, and acylating activity toward AF, affording
      AAF and FAF.

PMID- 11339232
TI  - Nutrition moves beyond weighty issues.

PMID- 11339233
TI  - Bill seeks to reform, educate on Medicare regulations.

PMID- 11339234
TI  - Image of the month. Salmonella aortitis.

PMID- 11339235
TI  - Glisson of Glisson's capsule of the liver.

PMID- 11339236
TI  - Successful orthotopic liver transplantation.

PMID- 11339237
TI  - Laparoscopic appendectomy in patients with refractory ulcerative colitis.

PMID- 11339238
TI  - Elevated levels of factor VIII:C as a possible risk factor for portal, splenic,
      and mesenteric vein thrombosis.

PMID- 11339239
TI  - Hepatitis B virus genotypes and hepatocellular carcinoma in Japan.

PMID- 11339240
TI  - Somatic mutation of the beta2-microglobulin gene associates with unfavorable
      prognosis in gastrointestinal cancer of the microsatellite mutator phenotype.

PMID- 11339241
TI  - Intractable insomnia after cessation of treatment with thalidomide.

PMID- 11339242
TI  - Results of carotid endarterectomy with prospective neurologist follow-up.

PMID- 11339244
TI  - Advances  in the genetics of cerebrovascular disease and stroke.
AB  - MEDLINE searches identified epidemiologic, experimental, and clinical studies on
      the genetics of cerebrovascular disease and stroke, including the following
      topics: genetic epidemiology of stroke; genetics of systemic disorders that cause
      ischemic stroke, including coagulation disorders, connective tissue disorders,
      vasculopathies, metabolic disorders, and disorders of unknown etiology; and
      genetics of systemic disorders that cause hemorrhagic stroke. Recent discoveries
      in stroke genetics involve the genetic basis of monogenic disorders such as
      cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy and sickle cell disease. Reproducing similar advances in
      other forms of cerebrovascular disease and stroke will be more difficult because
      their inheritance is complex, multigenic, and heterogeneous. However, the future
      is promising with the application of molecular genetic approaches such as linkage
      analysis, allele-sharing methods, association studies, and polygenic analysis of
      experimental crosses as well as the transmission/disequilibrium test--a
      statistical method for detection of linkage between a marker and a disease
      susceptibility locus.

PMID- 11339245
TI  - FAFLP: last word in microbial genotyping?

PMID- 11339246
TI  - Natural antibiotic susceptibility of Klebsiella pneumoniae, K. oxytoca, K.
      planticola, K. ornithinolytica and K. terrigena strains.
AB  - The natural susceptibility of 221 Klebsiella strains to 71 antibiotics was
      examined. The strains were isolated from clinical specimens and the environment,
      and belonged to K. pneumoniae subsp. pneumoniae (n = 40), K. pneumoniae subsp.
      ozaenae (37), K. pneumoniae subsp. rhinoscleromatis (10), K. oxytoca (44), K.
      planticola (40), K. ornithinolytica (25) and K. terrigena (25). MIC values were
      determined by a microdilution procedure in IsoSensitest broth according to the
      German standard (DIN). All Klebsiella spp. were naturally resistant or
      intermediate to amoxicillin, ticarcillin and to antibiotics to which other
      Enterobacteriaceae are also intrinsically resistant. Klebsiella spp. were
      naturally sensitive or intermediate to several penicillins, all tested
      cephalosporins, aminoglycosides, quinolones, tetracyclines, trimethoprim,
      cotrimoxazole, chloramphenicol and nitrofurantoin. K. pneumoniae subsp. ozaenae
      and subsp. rhinoscleromatis strains were generally more susceptible to
      antibiotics than strains of other Klebsiella taxa. K pneumoniae subsp.
      rhinoscleromatis was the most susceptible taxon, being highly susceptible to
      cefuroxime, anti-folates and naturally intermediate to erythromycin and
      clarithromycin. K. pneumoniae subsp. ozaenae was most susceptible to
      glycopeptides. K. oxytoca and K. terrigena strains were least susceptible to
      cefazoline, cefoperazone and fosfomycin, respectively. The results of the present
      study describe a database of the natural antimicrobial susceptibility of
      Klebsiella spp., which can be used for the validation of antibiotic
      susceptibility results of these bacteria. MIC patterns to beta-lactams indicate
      the expression of chromosomally encoded class A gamma-lactamases in all the
      species, including the subspecies of K. pneumoniae. Similar natural
      susceptibility patterns of K. planticola and K. ornithinolytica to all tested
      antibiotics support the status of K. ornithinolytica as a biovar of K.
      planticola.

PMID- 11339247
TI  - Molecular typing and long-term comparison of clostridium difficile strains by
      pulsed-field gel electrophoresis and PCR-ribotyping.
AB  - Thirty-two related and 68 unrelated isolates of Clostridium difficile, isolated
      in different Italian hospitals since 1987, were analysed by PFGE and PCR
      ribotyping to investigate their genetic relatedness. The isolates were classified
      into 28 groups by PFGE and 20 ribotypes by PCR-ribotyping. A single clone of C.
      difficile was recognised as the cause of three geographically and chronologically
      distant outbreaks. The correlation between PFGE and PCR-ribotyping results was
      good, with agreement for 77 (84%) of the 92 isolates typed by both methods.
      However, among sporadic isolates the discriminatory power of PFGE was more
      evident. Eight isolates that were untypable by PFGE could be analysed by PCR
      ribotyping. The dendrograms generated showed that the genetic relatedness of the
      C. difficile isolates obtained by both techniques was comparable. The majority of
      the isolates in recent years appeared to be genetically unrelated to isolates
      from past infections. However, two clonal groups identified in all time periods
      had a common origin and this seems to indicate that they share some advantageous
      biological characteristics. The constant monitoring of C. difficile epidemiology
      will allow acquisition of further important data on this nosocomial pathogen.

PMID- 11339248
TI  - An attempt to identify the evolutionary origin of a novel serotype of Salmonella
      enterica isolated from harbour porpoises.
AB  - The isolation since 1991 of a new serotype of Salmonella enterica (antigenic
      formula 4,12:a:-) from harbour porpoises (Phocoena phocoena) at post-mortem
      examination raised the question of its evolutionary origin. Representative
      strains of S. enterica serotype 4,12:a:- and strains of eight other serotypes of
      serogroup 04 with phase-1 flagellar antigen H 'a' were examined by EcoRI
      ribotyping, IS200 fingerprinting and PCR-based profiling. Statistical analysis of
      results of multiple typing showed that strains of Salmonella serotype 4,12:a:-
      were genetically distant from those of antigenically similar salmonella
      serotypes, none of which seemed likely to be the progenitor of the 'porpoise'
      serotype.

PMID- 11339249
TI  - Novel Helicobacter species isolated from rhesus monkeys with chronic idiopathic
      colitis.
AB  - Chronic, idiopathic diffuse colitis is a well recognised clinical and
      pathological entity in captive rhesus monkeys. Six rhesus monkeys were diagnosed
      with clinically debilitating, chronic diarrhoea. Histologically, colonic tissues
      were characterised as chronic, moderate to severe colitis and typhlitis, with
      diffuse mononuclear inflammation of lamina propria, reactive lymphoid hyperplasia
      and multifocal micro-abscesses. Colonic tissues were cultured for Salmonella spp.
      and Shigella spp.; all results were negative. Samples were negative for
      Clostridium difficile A and B toxins, and special stains of colonic tissue for
      acid-fast bacteria were also negative. The six diarrhoeic monkeys tested gave
      negative results for serum IgG antibodies to herpes B virus, STLV, SRV and SIV.
      Colonic tissue from the six diarrhoeic and two clinically normal monkeys with
      histologically confirmed colitis from the same colony were also subjected to
      micro-aerobic culture. Micro-aerobic cultures from all eight monkeys incubated at
      37 degrees C and 42 degrees C revealed pinpoint or spreading colonies on
      antibiotic-containing media. Bacteria were identified as gram-negative, oxidase
      positive and urease negative. Of the nine strains characterised biochemically,
      two separate biotypes (corresponding to different species by 16S rRNA analysis)
      were identified. One biotype (type 1), from non-diarrhoeic monkeys and the second
      biotype (type 2) from diarrhoeic animals with subclinical chronic colonic
      inflammation, differed by catalase activity, ability to reduce nitrate to nitrite
      and sensitivity to cephalothin. Complete 16S rRNA analysis of five of the nine
      strains characterised biochemically indicated that the organisms isolated were
      two novel Helicobacter spp. By electron microscopy, these novel helicobacters had
      spiral morphology with bipolar sheathed flagella. This is the first report
      describing the isolation of novel Helicobacter spp. from inflamed colons of
      rhesus monkeys. Studies are needed to determine whether these novel Helicobacter
      spp. play a causal role in the initiation and progression of chronic colitis in
      macaques. Further microbiological and histological analysis of this chronic
      idiopathic colitis syndrome in macaques may prove useful in understanding the
      aetiology and pathogenesis of inflammatory bowel disease in man.

PMID- 11339250
TI  - Inhibition of Helicobacter pylori infection by bovine milk glycoconjugates in a
      BAlb/cA mouse model.
AB  - The attachment of Helicobacter pylori to the human gastric mucosa is a complex
      process involving several specific structures recognised by the cell surface
      receptors. Sialylated multivalent high mol. wt glycoproteins have been shown to
      inhibit H. pylori sialic acid-specific haemagglutination. This study explored
      whether sialylated glycoconjugates from bovine milk could inhibit an experimental
      H. pylori infection in a mouse model. BALB/cA mice (6-8 weeks old) were
      inoculated with a mouse-passaged H. pylori strain 317p. Four weeks after
      infection the mice were given lactoferrin (iron-free LF or 20% iron-saturated LF)
      or bovine milk fat globule membrane fractions (MFGM or defatted MFGM) orally (400
      mg/kg body weight) once daily for 10 days and then killed to examine for
      bacterial colonisation and gastritis. Mice treated with iron-free LF, 20% iron
      saturated LF, MFGM or defatted MFGM showed 30%, 10%, 20% or 20% healing rates,
      respectively, when compared with the H. pylori-infected control. Gastric
      colonisation by H. pylori was remarkably decreased in all mice treated with
      bovine milk glycoconjugates and the inflammation score was also significantly
      lower in treated mice than in infected control animals. The fact that there was
      no significant difference between iron-free LF and iron-saturated LF or MFGM and
      defatted MFGM suggested that iron is not crucial for inhibition of H. pylori by
      lactoferrin and that the lipid part of MFGM is not important for anti-H. pylori
      activity. In conclusion, bovine milk glycoconjugates showed potencies to inhibit
      H. pylori infection in this mouse model and, therefore, could be considered as
      candidates for non-antibiotic strategies against H. pylori infection in man.

PMID- 11339251
TI  - Evaluation of a real-time PCR assay for detection of Bordetella pertussis and B.
      parapertussis in clinical samples.
AB  - A real-time PCR assay based on the TaqMan technology was developed for the
      detection of Bordetella pertussis and B. parapertussis in clinical samples. The
      assay was evaluated with 182 specimens from 153 patients with and without
      symptoms of pertussis. The analytical sensitivity ranged from 0.1 to 10 cfu for
      B. pertussis and B. parapertussis, respectively, and diagnostic sensitivity was
      94.1% when culture was used as a reference. No sample from a patient without
      symptoms of pertussis was positive in PCR. Twenty-four of 28 patients who were
      negative by culture and positive by PCR assay met the CDC clinical case
      definition for pertussis; the remaining four patients had paroxysms of shorter
      duration. Intra- and inter-assay variation were <5% and results were available
      within 4 h.

PMID- 11339252
TI  - Single primer pair for PCR identification of Candida parapsilosis group I
      isolates.
AB  - A DNA fragment, isolated from a genomic DNA mini-library of Candida parapsilosis
      group I reference strain ATCC 22019, was sequenced and characterised. The
      fragment was first probed by Southern blotting against a pool of DNA from several
      yeasts. The hybridisation tests revealed that the probe was specific for strain
      ATCC 22019 and 49 (90.74%) of 54 C. parapsilosis clinical and soil isolates that
      were attributed to C. parapsilosis group I by the electrophoretic images of their
      restriction fragment length polymorphisms (RFLPs) and electrophoretic karyotype
      (EK). The remaining five negative isolates, according to the same criteria, were
      attributed to group II (one isolate) and III (four isolates). Two primers were
      selected from the probe DNA sequence and a PCR-based test was developed for
      specifically detecting C. parapsilosis group I isolates, which represent the
      majority of the common clinical isolates. The PCR assay confirmed the Southern
      hybridisation results. This PCR assay could be a simple and reproducible tool for
      the rapid, sensitive and species-specific identification of C. parapsilosis major
      group I isolates.

PMID- 11339253
TI  - The effect of temperature on the interaction of Haemophilus ducreyi with human
      epithelial cells.
AB  - To investigate if temperature affects the interaction of Haemophilus ducreyi with
      human epithelial cells, nine strains were used to evaluate the adhesion kinetics
      of the organism at 33 degrees C and 37 degrees C. The effect of the free toxin on
      the epithelial cells at those temperatures was also assessed. The cyto-adherence
      kinetics of H. ducreyi to the epithelial cells was significantly greater at 33
      degrees C (10 times more) than at 37 degrees C in all seven clinical isolates
      tested. There was a significant difference in cell-associated H. ducreyi at 33
      degrees C as compared with 37 degrees C. Control strains showed similar adhesion
      properties at both temperatures. However, the virulent strain CIP542 adhered in
      larger amounts than the avirulent strain A77. Electron microscopy revealed that
      there was more tissue necrosis at the lower than the higher temperature. The
      effect of the free toxin was the same at each temperature. However, strain A77
      had significantly lower toxicity than strain CIP542 and the clinical isolates.
      These results suggest that H. ducreyi displays a temperature-dependent
      interaction with human epithelial cells, and this feature may play a role in the
      virulence of the organism in vivo. While the overall toxic effect of viable
      bacteria depends on the metabolic activity of the bacteria and is, therefore,
      higher at 33 degrees C than at 37 degrees C withthe same initial inoculum, the
      effect of the extracted toxin at molecular level with fixed concentrations is a
      temperature-independent event.

PMID- 11339254
TI  - Induction of interleukin-10 and down-regulation of cytokine production by
      Klebsiella pneumoniae capsule in mice with pulmonary infection.
AB  - The role of the capsule of Klebsiella pneumoniae in inducing cytokine production
      was investigated by comparing the responses of mice with experimentally induced
      pneumonia caused by capsulate (strain DT-S) or non-capsulate (mutant strain DT-X)
      K. pneumoniae. Anaesthetised ICR mice were inoculated intranasally. Whereas all
      DT-S-infected mice died within 3 days, no deaths were observed in DT-X-infected
      mice by 14 days after infection. During the early stage of infection, interferon
      gamma (IFN-gamma) levels in bronchoalveolar lavage fluid (BALF) of DT-X-infected
      mice were significantly higher than those in DT-S-infected mice. In contrast, in
      the late stage of infection, serum levels of granulocyte macrophage-colony
      stimulating factor (GM-CSF) and IFN-gamma in DT-S-infected mice were
      significantly higher than those in DT-X-infected mice. Levels of interleukin10
      (IL-10) in BALF and serum of DT-S-infected mice were significantly and
      persistently higher than those of DT-X-infected mice. The IL-10/TNF-alpha (tumour
      necrosis factor-a) ratios in BALF and serum indicated that higher levels of IL-10
      production were induced in mice infected with strain DT-S than in those infected
      with strain DT-X. The results suggest that the capsule of K. pneumoniae may
      induce IL-10 production at the site of infection and, thereafter, these high IL
      10 levels may serve to down-regulate the expression of pro-inflammatory
      cytokines.

PMID- 11339255
TI  - Characterisation and phylogenetic analysis of the VP7 proteins of serotype G6 and
      G8 human rotaviruses.
AB  - Serotype G6 and G8 rotaviruses are rarely found in man and may have originated in
      animals. Human serotype G6 and G8 rotaviruses, isolated from hospitalised
      children at various locations in Australia, were characterised. Deduced amino
      acid sequences of the major neutralising antigen, V7, showed significant identity
      to the cognate proteins of prototype human and bovine G6 and G8 viruses,
      respectively, and the strains reacted with G6 and G8 serotype-specific
      neutralising monoclonal antibodies, respectively, in an enzyme immunoassay. The
      VP4 type was determined as P[14] for all strains tested. Phylogenetic analysis of
      these and other human and bovine VP7 sequences suggested that a single inter
      species transmission event, possibly from cattle, may have led to the emergence
      of G6 viruses in man. In contrast, the exchange of genes between human and bovine
      G8 viruses may have occurred onmore than one occasion, or these genes may have
      originated in a different host.

PMID- 11339256
TI  - Poor antibody response against human papillomavirus in adult-onset laryngeal
      papillomatosis.
AB  - To investigate whether adult-onset laryngeal papillomatosis induces serum
      antibodies to the human papillomavirus (HPV), 60 patients underwent a clinical
      examination, and HPV DNA from their laryngeal biopsy was assayed by PCR and HPV
      serology with virus-like particles as the antigen. Patients and controls (n = 53)
      showed no differences in their HPV 6 and 16 antibodies. Patients more often had
      HPV 11 antibodies, female patients more often than female controls or male
      patients. Of the female patients, 5 of 15 had a history of genital condylomas
      and, at the follow-up visit, 5 of 9 had cervical cytology consistent with genital
      HPV infection. The fact that HPV antibodies did not correlate with clinical
      features of the laryngeal disease or with HPV DNA detected in the larynx,
      suggests that HPV antibodies in female patients were induced by genital rather
      than laryngeal HPV infection. The high prevalence of abnormal Pap smears
      indicates that gynaecological examination of female adult-onset laryngeal
      papilloma patients is warranted.

PMID- 11339257
TI  - A comparison of the performance of bacitracin-incorporated chocolate blood agar
      with chocolate blood agar plus a bacitracin disk in the isolation of Haemophilus
      influenzae from sputum.
AB  - The lack of selectivity of chocolated blood agar (CBA), routinely used for the
      isolation of Haemophilus influenzae, may lead to masking of the growth of H.
      influenzae due to overgrowth of competing flora. Bacitracin can be used as a
      selective agent, either incorporated into the medium or applied to the medium in
      a filter paper. However, neither method has been evaluated or compared in a large
      study. Sputum samples (1990) were examined in four laboratories and the isolation
      rates of H. influenzae on chocolated blood agar with bacitracin added to the
      medium (BCA) and chocolated blood agar (CBA) with a bacitracin disk were
      compared. A plain blood agar plate was also inoculated to facilitate the
      isolation of Streptococcus pneumoniae so that its effects on the isolation of H.
      influenzae could be assessed. No significant difference was found between the
      isolation rates of H. influenzae on BCA and CBA with a bacitracin disk, although
      competing flora was greatly reduced and quantity of growth of H. influenzae
      increased on BCA. The presence of S. pneumoniae did not affect the isolation of
      H. influenzae in this study.

PMID- 11339258
TI  - Evaluation of a new selective medium for methicillin-resistant Staphyloccocus
      aureus.
AB  - The aims of this study were to evaluate the performance of a new medium,
      desferrioxamine oxacillin tellurite egg-yolk mannitol salt agar (DOTEMSA) in
      detecting methicillin-resistant Staphylococcus aureus (MRSA) and then to compare
      this medium against the Public Health Laboratory Service (PHLS) recommendation of
      mannitol salt agar (Oxoid) with oxacillin (OMSA) and Baird-Parker medium with
      ciprofloxacin (BPC) for the isolation of MRSA. The individual selective agents
      contained in DOTEMSA were tested against isolates of coagulase-negative
      staphylococci (CNS) and the medium with all constituents was challenged with
      various bacteria. Routine screening specimens were plated out on OMSA, BPC and
      DOTEMSA and the plates were incubated and examined at 24 and 48 h. Tellurite,
      desferrioxamine and oxacillin each inhibited the majority of CNS isolates; only
      three (of 103) grew in the presence of all three agents. Sixty-two of 63 isolates
      of MRSA grew on DOTEMSA and 59 produced lipase. Most other bacteria were
      inhibited. In all, 184 MRSA isolates were isolated from 540 screening specimens.
      The sensitivity of OMSA, BPC and DOTEMSA was 42%, 81% and 51% at 24 h, and 60%,
      89% and 89% at 48 h. At 48 h, the combination of BPC and DOTEMSA detected 99% of
      MRSA isolates. Seventy, 49 and one non-MRSA isolates needed investigation for
      each of the three media respectively. A proposed strategy for MRSA screening
      would use BPC and DOTEMSA, examining BPC at 24 h and both media at 48 h.
      Provisional reports could then be issued at 24 h on the basis of rapid
      agglutination tests to confirm isolates as S. aureus from BPC and at 48 h on the
      basis of typical colonies from DOTEMSA.

PMID- 11339259
TI  - Iliac osteomyelitis and gluteal muscle abscess caused by Streptococcus
      intermedius.
AB  - Streptococcus intermedius, included in the 'milleri group', is a commensal of the
      mouth and upper respiratory tract but it has often been associated with various
      pyogenic infections, such as endocarditis, pneumonia, abdominal or cerebral
      abscess, rarely with osteomyelitis, and exceptionally with muscular abscess. The
      first observed case of iliac osteomyelitis with gluteal muscle abscess caused by
      S. intermedius is reported. It is essential to recognise members of the 'milleri
      group' as possible agents of bone and muscle pyogenic infection because its
      management requires a timely diagnosis and prolonged antimicrobial treatment to
      achieve complete clinical and radiological recovery.

PMID- 11339260
TI  - The effects of domestic cooking on the levels of 3-monochloropropanediol in
      foods.
AB  - The results are reported of a study to determine the effect of domestic cooking
      procedures on the level of 3-monochloropropane-1,2-diol (3-MCPD) in selected
      foods. Samples of 23 foods comprising stock cubes, gravies, a cake mix, batters,
      breads, cheese and meats were subjected to a range of cooking procedures
      including grilling, toasting and microwaving. The resulting levels of 3-MCPD were
      compared with those present in the foods before cooking. Grilling and toasting
      produced substantial increases in the 3-MCPD content of bread, forming up to 0.3
      mg/kg, and of most cheeses, resulting in levels of up to about 0.1 mg/kg.
      Microwave cooking produced elevated 3-MCPD levels in some cheeses. Frying
      laboratory-produced batters increased 3-MCPD levels to about 0.1 mg/kg whereas a
      retail batter contained no detectable 3-MCPD when fried. The remaining foods
      showed little or no discernible increase on cooking.

PMID- 11339261
TI  - Isolation and identification of main constituents in an enzymatically hydrolysed
      licorice extract sweetener.
AB  - Licorice extract including glycyrrhizin as the major component is used as a safe
      sweetener in many countries. Enzymatically hydrolysed licorice extract (EHLE) is
      also used as a sweetener in Japan. In the present paper, the constituents of EHLE
      were investigated as a part of the studies for evaluating its quality and safety
      as a food additive. Three oleanane-type monoglycosides along with glycyrrhizin
      (1) eand 3-O-[beta-D-glucuronopyranosyl-(1-->2)-beta-D-glucuronopyranosyl]-18beta
      liquiritic acid (2) were isolated from EHLE. The structures of the three
      compounds have been determined to be 3-O-beta-D-glucuronopyranosyl-24-hydroxy
      18beta-glycyrrhetinic acid (3), 3-O-beta-D-glucur-onopyranosyl-18beta
      glycyrrhetinic acid (4) and 3-O-beta-D-glucuronopyranosyl-18beta-liquiritic acid
      (5) based on MS and NMR. Compound 4 was the monoglycosylated derivactive of
      glycyrrhizin (1). Compounds 3 amd 5 are the monoglycosylated derivatives of the
      minor constituents in licorice extract. They were first isolated from EHLE, and
      compound 5 was a new compound.

PMID- 11339262
TI  - A sensitive enzyme immunoassay (EIA) for the determination of melengestrol
      acetate (MGA) in adipose and muscle tissues.
AB  - The development of a sensitive screening method of MGA residues in bovine
      perirenal fat and muscle based on a competitive microtitration plate enzyme
      immunoassay is described. The samples were extracted with petroleum ether and
      purified with octadecyl-silica-cartridges. The detection limit for fat was 0.4
      ng/g andfor muscle tissue 0.05 ng/g, much lower than requiredfor reliable
      detection of positive samples. The mean recovery rates of fortified samples
      amount to 75%, the mean intraassay variations to 7% and the interassay variation
      to 13%. Determination limits were validated for fat at 2 ng/g and for muscle at
      0.1 ng/g. The efficiency of the new screening method was successfully
      demonstrated by the direct comparison to GC-MS and LC-MS methods performed at
      natural positive samples originating from an animal experiment in which the
      labelled dose (0.5 mg per animal and day) with and without a 48 h withdrawal
      period or 3-fold or 10-fold the amount of MGA, respectively, was fed to Holstein
      Frisian heifers. In conclusion, this new screening method can be used for
      sensitive determination of MGA residues in adipose tissues even after low
      treatment doses or longer withdrawal periods.

PMID- 11339263
TI  - Tetracycline residues in meat and bone meals. Part 1: methodology and examination
      of field samples.
AB  - The incidence of tetracycline residues in commercially available samples of meat
      meals and meat and bone meals was investigated. Four different methods were used
      on each of the 87 samples from nine different rendering plants in Germany:
      examination using a screening fluorescence test; examination by high performance
      liquid chromatography analysis using three different extraction procedures
      (succinate buffer, hydrochloric acid, hydrochloric acid after sedimentation of
      bone particles). Tetracyclines were found in 100% of the samples by one or more
      of the extraction procedures. The highest concentrations found in meat meals were
      2048 microgkg(-1), 1393 microgkg(-1) and 608 microgkg(-1) for oxytetracycline,
      tetracycline and chlortetracycline, respectively. In meat and bone meals the
      highest concentrations were 2295 microg oxytetracycline kg(-1) 848 microg
      tetracycline kg(-1) and 1274 microg chlortetracycline kg(-1). The extraction
      after sedimentation was the most effective of the applied extraction procedures
      and exposed the highest total tetracycline concentrations. The results of this
      investigation showed that considerable amounts of tetracyclines have to be
      expected in field samples. Further research has to be done on the heat stability
      of bound tetracycline residues.

PMID- 11339264
TI  - Consumption of bivalve molluscs in Italy: estimated intake of cadmium and lead.
AB  - Concentrations of cadmium and lead were determined in nine different species of
      mollusc bivalves (Modiolus barbatus, Venus verrucosa, Scapharca inaequivalvis,
      Tapes decussatus, Callista chione, Pecten jacobeus, Ensis siliqua, Venus gallina,
      Cardium tubercolata) collected from different coastal areas of the Adriatic Sea
      (north, middle and south Adriatic). The levels of cadmium and lead found in
      bivalves from the north Adriatic Sea were significantly (P < 0.001) higher than
      those detected in those from the middle and south Adriatic Sea. In some species
      of molluscan bivalves (M. barbatus and T. decussatus) from the north Adriatic
      Sea, concentrations of cadmium and lead exceeded the maximum limit (2 mg/kg w.w.)
      established by the Italian legislation. Weekly intakes were estimated and
      compared with the Provisional Tolerable Weekly Intake (PTWI) recommended by the
      FAO/WHO Expert Committee on Food Additives.

PMID- 11339265
TI  - Degradation of the insecticide azinphos methyl in orange and peach juices during
      storage at different temperatures.
AB  - The degradation of azinphos methyl in orange and peach juice was studied. The
      insecticide was aseptically added to packed orange and peach juices and stored at
      40, 20 and 0 degrees C. Samples were removed at regular intervals and were
      analysed for residues of azinphos methyl. Residues were determined with a simple
      gas-chromatographic method using a 30 m glass capillary column and an NP
      detector. The recoveries of azinphos methyl were 87-110% for orange juice and 92
      108% for peach juice, and the limit of determination was 0.004 mg/kg for both
      juices. From the experimental data, rate constants, half-lives, and times needed
      to reach legal limits for the decomposition of azinphos methyl in orange and
      peach juices were evaluated. Half lives for orange and peach juices were 6.5 and
      7.8 days at 40 degrees C, 86.6, and 92.4 days at 20 degrees C, and 407.7 and
      495.1 days at 0 degrees C, respectively.

PMID- 11339266
TI  - Aflatoxins in spices marketed in Portugal.
AB  - Seventy-nine prepackaged samples of 12 different types of spice powders (five
      cardamom, five cayenne pepper, eight chilli, five cloves, seven cumin, five
      curry) powder, five ginger, five mustard, 10 nutmeg, 12 paprika, five saffron and
      seven white pepper) were selected from supermarkets and ethnic shops in Lisbon
      (Portugal) for estimation of aflatoxins by immunoaffinity column clean-up
      followed by HPLC. Aflatoxin B1 (AFB1) was detected in 34 samples of prepackaged
      spices (43.0%). All of the cayenne pepper samples were contaminated with levels
      ranging from 2 to 32 microg AFB1/kg. Three nutmeg samples contained levels
      ranging from 1 to 5 microg/kg, three samples had levels ranging from 6 to 20
      microg/kg, and there were two with 54 microg/kg and 58 microg/ kg. Paprika
      contained levels of aflatoxin B1 ranging from 1 to 20 microg/kg. Chilli, cumin,
      curry powder, saffron and white pepper samples had levels ranging from 1 to 5
      microg/kg. Aflotoxins were not detected in cardamon, cloves, ginger and mustard.
      None of the samples analysed contained aflatoxins B2, G1 and G2.

PMID- 11339267
TI  - Presence of ochratoxin A in human milk in relation to dietary intake.
AB  - Individual and geographical variations in ochratoxin A (OA) levels in human blood
      and milk samples may be due to differences in dietary habits. The purpose of this
      study was to examine the relationship between OA contamination of human milk and
      dietary intake. Human milk samples were collected from 80 Norwegian women. The
      usual food intake during the last year was recorded using a quantitative food
      frequency questionnaire. The concentration of OA in the human milk was determined
      by HPLC (detection limit 10 ng/l). Seventeen (21%) out of 80 human milk samples
      contained OA in the range 10-182 ng/l. The women with a high dietary intake of
      liver paste (liverwurst, liver pate) and cakes (cookies, fruitcakes, chocolate
      cakes, etc.) were more likely to have OA-contaminated milk. The risk of OA
      contamination was also increased by the intake of juice (all kinds). In addition,
      the results indicate that breakfast cereals, processed meat products, and cheese
      could be important contributors to dietary OA intake. OA contamination of the
      milk was unrelated to smoking, age, parity, and anthropometric data other than
      body weight.

PMID- 11339268
TI  - Genotoxicity testing of extracts from aflatoxin-contaminated peanut meal,
      following chemical decontamination.
AB  - One of the most important concerns in the decontamination of aflatoxin-containing
      feed commodities is the safety of the products for food-producing animals and for
      human consumption of products derived from these animals. A new method, based on
      the use of florisil and C18 solid phase extraction columns, was developed for the
      preparation of extracts from decontaminated peanut meal, which allowed testing
      with in vitro genotoxicity assays without interference of the residual aflatoxin
      B1. Recovery of degradation products in the extracts was evaluated by the use of
      radiolabelled [14C]-aflatoxin B1 (AFB1) added to naturally-contaminated peanut
      meal (3.5 mg AFB1/kg). The meal was treated by a small-scale version of an
      industrial decontamination process based on ammoniation. Following
      decontamination, more than 90% of the label could not be extracted from the meal.
      AFB1 accounted for about 10% of the radiolabel present in the extractable
      fraction, indicating a total AFB1 reduction of more than 99%. Decontamination of
      the meal by a number of other small- and industrial-scale ammonia-based processes
      resulted in similar efficiencies. Application of the extraction procedure
      resulted in AFB1-rich and AFB1-poor fractions, the latter containing half of the
      extractable decontamination products but less than 1% of the residual AFB1.
      Testing in the Salmonella/microsome mutagenicity assay (TA 100, with S9-mix) of
      the original crude extracts and AFB1-rich fractions prepared from non-treated and
      decontaminated meal, showed the positive results expected from the AFB1 contents
      as determined by HPLC analysis. Analysis and testing of the AFB1-poor fractions
      showed that the various decontamination processes not only resulted in a
      successful degradation of AFB1 but also did not produce other potent mutagenic
      compounds. Slight positive results obtained with these extracts were similar for
      the untreated and treated meals and may be due to unknown compounds originally
      present in the meal. Results obtained with an unscheduled DNA synthesis (UDS) and
      Comet assay with rat hepatocytes supported this conclusion. Positive results
      obtained with the micronucleus assay, using immortalized mouse hepatocytes (GKB),
      did not clearly reflect the mycotoxin levels and require further examination. It
      is concluded that the newly developed extraction procedure yields highly
      reproducible fractions and hence is very suitable for examining the possible
      formation of less potent degradation products of aflatoxins in short-term
      genotoxicity tests.

PMID- 11339269
TI  - Polymer additive migration to foods--a direct comparison of experimental data and
      values calculated from migration models for polypropylene.
AB  - To reduce the amount of compliance testing for food contact polymers the use of
      migration modelling is under discussion and being evaluated by an EU Commission
      funded project (Evaluation of Migration Models No. SMT4-CT98-7513). The work
      reported in this paper was exclusively funded by industry to provide data for the
      independent evaluation of a diffusion based model using eight different samples
      of polypropylene (PP) covering the range of polymers specification and five
      commonly used plastics additives. One hundred and fifty experimental migration
      data have been obtained in triplicate and used to evaluate a Fickian-based
      migration model in the prediction of specific migration of five additives into
      olive oil. All tests were conducted using olive oil, representing the most severe
      case for fatty foods, with test conditions of 2h at 121 degrees C, 2h at 70
      degrees C and 10 days at 40 degrees C, representing short term exposures at high
      temperatures and room temperature storage. Predicted migration values were
      calculated using the Piringer 'Migratest Lite' model by entering the measured
      initial concentration of additive in the polymers(Cp.0) in to the equations
      together with known variables such as additive molecular weight, temperature and
      exposure time. Where necessary the data generated in this study have been used to
      update the model. The results indicate the Piringer migration model, using the
      'exact' calculations of the Migratest Lite program, predicted migration values
      into olive oil close to, or in excess of, the experimental results for > 97% of
      the migration values generated in this study. For all measurements, the predicted
      migration from the Migratest Lite program was greater than 70% of the observed
      value. This study has identified the possibility, that random co-polymers of
      propylene and ethylene give higher migration than other grades of polypropylenes
      and could be treated as a separate case. However, further work on more samples of
      random co-polymers is required to confirm this finding.

PMID- 11339270
TI  - Analysis of plasticizers in cap-sealing resins for bottled foods.
AB  - A survey of plasticizers in cap-sealing resins for bottled foods has been
      undertaken. During 1997-1999 di-(2-ethylhexyl)phthalate (DEHP) was found in seven
      out of 21 samples on the Japanese domestic market and in 10 out of 61 imported
      samples as well as a further two samples which contained di-(2-ethylhexyl)adipate
      (DEHA). In the period 1993-1999, of the other plasticizers diacetyl lauroyl
      glycerol (DALG) was only detected in domestic samples whereas diisodecyl
      phthalate (DIDP) and diisononyl phthalate (DINP) were only in imported samples.
      It was observed overall that DEHP and DEHA were restricted to use in cap-sealing
      resins for bottled foods. Whilst phthalates, DEHA or DALG were detected in
      samples in 1993 and 1995, the investigation in 1997-1999 showed fewer samples in
      which these plasticizers were found.

PMID- 11339271
TI  - High-performance liquid chromatography determination of flunitrazepam and its
      metabolites in plasma by use of column-switching technique: comparison of two
      extraction columns.
AB  - A study, using on-line column-switching high-performance liquid chromatography,
      evaluated two different extraction columns for the determination of flunitrazepam
      and its major metabolites: 7-aminoflunitrazepam, 7-acetamidoflunitrazepam and
      desmethylflunitrazepam. The procedure was based on the enrichment of
      benzodiazepines on the extraction column, followed by transfer of the compounds
      to the analytical column. The two extraction columns were compared: the first
      column was a BioTrap 500 MS (hydrophobic polymer), 20x4 mm I.D., and the second
      was a LiChrospher RP-18 ADS, 25x4 mm I.D. The analytical column used was a
      LiChrospher select B RP-8, 125x3 mm I.D. with 5 microm particle size. The
      extraction conditions for the two pre-concentration columns, such as extraction
      temperature, buffer concentration, buffer pH, acetonitrile percentage and flow
      rate, were studied for the extraction from plasma of flunitrazepam and its
      metabolites mentioned above. The mobile phase of the analytical column was
      isocratic and composed of acetonitrile-20 mM phosphate buffer at pH 2.1 (35:65,
      v/v) and at a flow-rate of 0.3 ml/min.

PMID- 11339272
TI  - Simultaneous determination of Ziagen and its phosphorylated metabolites by ion
      pairing high-performance liquid chromatography-tandem mass spectrometry.
AB  - An ion-paring HPLC-MS-MS method with positive ion mode electrospray ionization
      has been developed to simultaneously quantify Ziagen, carbovir monophosphate,
      carbovir diphosphate and carbovir triphosphate. N',N'-Dimethylhexylamine was used
      as the ion-pairing agent. The presence of this ion-pairing agent allowed the
      retention and separation of the four compounds on a reversed-phase HPLC column as
      well as the detection of the nucleotides with positive ion mode electrospray
      ionization. The limits of detection were found to be better than 25 nM for all
      the analytes. Calibration curves of the analytes showed excellent linearity over
      the range of 25 nM to 5 microM. The relative standard deviations and accuracies
      for replicate analyses of quality control samples were less than 15%. The method
      has been successfully applied to the analysis of these compounds in human liver
      cells treated with Ziagen.

PMID- 11339273
TI  - Determination and structural characterisation of dermatan sulfate in the presence
      of other galactosaminoglycans.
AB  - Chondroitin sulfate and dermatan sulfate are galactosaminoglycans that have
      similar size and charge density thus making difficult their separation and
      accurate determination from tissue preparations. A procedure was developed, which
      was based on the specific action of chondroitinase B, that allowed the
      determination of dermatan sulfate content in a mixture of chondroitin
      sulfate/dermatan sulfate, its molecular mass (Mr), and iduronic acid content and
      distribution throughout the chain. According to this procedure, the
      galactosaminoglycan sample was treated with chondroitinase B and its profile,
      upon gel chromatography on Sepharose CL-6B, was compared to that of the initial
      sample. The differences in uronic acid content of the fractions of the gel
      chromatographies were plotted and a secondary profile was constructed, which
      corresponded to the elution profile of intact dermatan sulfate in the sample.
      From this profile, the size distribution of dermatan sulfate was obtained and its
      Mr was calculated. In addition, the accurate content of dermatan sulfate in the
      sample was determined. The digest contained oligosaccharides of variable size
      that were separated on BioGel P-10. From the separated oligosaccharides the
      distribution of iduronic acid throughout the dermatan sulfate chains was
      determined. The procedure was applied to the determination and partial
      characterisation of dermatan sulfate from sheep nasal cartilage, in which it is
      reported for the first time that it contains a significant proportion of dermatan
      sulfate chains of low iduronic acid content.

PMID- 11339274
TI  - Validation of an analytical procedure for the determination of the
      fluoroquinolone ofloxacin in chicken tissues.
AB  - A novel analytical procedure was developed for the determination of the
      fluoroquinolone ofloxacin in chicken kidney, liver, muscle and fat plus skin
      tissues. The procedure involved a preliminary extraction with 0.15 M HCl followed
      by solid-phase extraction clean-up. The purification step was performed using a
      polymeric sorbent coated cartridge. Ofloxacin was analyzed by reversed-phase HPLC
      using UV detection at 295 nm. The mobile phase used was water-acetonitrile
      triethylamine (83:14:0.45, v/v, pH 2.30). The use of triethylamine and the acidic
      pH modulated the retention of ofloxacin and avoided chemical tailing. The amine
      modifier and acetonitrile content of the mobile phase were optimized to provide
      the best selectivity. A flow-rate of 1 ml/min was used and ofloxacin eluted at
      approximately 5.1 min. HPLC analysis of the tissue samples was performed in 12
      min. The procedure was validated according to the International Conference on
      Harmonisation guidelines across the concentration ranges (100 microg/kg-1.7 mg/kg
      for kidney and liver tissues and 50 microg/kg-1.0 mg/kg for muscle and fat plus
      skin tissues). The linearity, the intra- and inter-day accuracies and precisions
      were determined. The limits of quantification were 50 microg/kg for muscle and
      fat plus skin tissues and 100 microg/kg for liver and kidney tissues. The
      procedure was specific and the accuracy values were lower than 20% at the limit
      of quantitation of spiked samples. The recovery values ranged from 80 to 100%.
      The limits of detection were established at 60 microg/kg for liver and kidney
      tissues and at 25 microg/kg for muscle and fat plus skin tissues. Finally,
      ofloxacin was found to be stable in acidic conditions. The developed procedure is
      simple, sensitive, accurate and adapted to routine sample analyses such as those
      carried out for residue depletion studies.

PMID- 11339275
TI  - High-performance liquid chromatography-electrospray ionization mass spectrometry
      method for the measurement of moclobemide and two metabolites in plasma.
AB  - A rapid and sensitive liquid chromatography-electrospray ionisation mass
      spectrometry (HPLC-ESI-MS) assay has been developed for the measurement of
      moclobemide and metabolites, Ro12-5637 and Ro12-8095, in human plasma. Sample
      preparation (0.5 ml plasma) involves solid-phase extraction using C18 cartridges.
      A Nova-Pak phenyl column (Waters, 4 microm, 150x2 mm I.D.) was employed for
      analyte separation with a mixture of 0.2 M ammonium formate buffer, pH 3.57 and
      acetonitrile as the mobile phase. The within- and between-day precisions of the
      assay were <18% and the limit of quantification for all analytes was 0.01
      microg/ml. The total run-time was 6 min. The method described was used to measure
      moclobemide, Ro12-5637 and Ro12-8095 in human plasma following an oral 300 mg
      dose.

PMID- 11339276
TI  - Analysis of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors using
      liquid chromatography-electrospray mass spectrometry.
AB  - Employing high-performance liquid chromatography-electrospray mass spectrometry,
      we describe a new assay for monitoring 3-hydroxy-3-methylglutaryl-coenzyme A (HMG
      CoA) reductase activity. Incubations were carried out with HMG-CoA reductase (rat
      liver), HMG-CoA and NADPH, and terminated by the addition of HCl. The reaction
      product, mevalonolactone, and internal standard, were extracted with ethyl
      acetate, dissolved in methanol, and analyzed by LC-MS. Using an isocratic mobile
      phase of 10% acetonitrile and 0.1% formic acid (flow-rate, 0.2 ml/min), the
      protonated molecules of mevalonolactone at m/z 131 and internal standard,
      beta,beta-dimethyl-gamma-(hydroxymethyl)-gamma-butyrolactone, at m/z 145, were
      detected using selected ion monitoring. The limit of detection was approximately
      6.5 pg, and the limit of quantitation was approximately 16.3 pg. Extraction
      recovery was >90%. The relative standard deviations for intra- and inter-day
      assays were approximately 4.1+/-2.7 and 9.4+/-3.4%, respectively. Mevalonolactone
      was examined over a period of 3 days and found to be stable. Using this assay,
      lovastatin and mevastatin inhibited HMG-CoA reductase activity with IC50 values
      0.24+/-0.02 and 2.16+/-0.31 microM, respectively. These methods offer some
      advantages over those reported previously which employ radiolabeled substrate and
      products, and should be useful in searching for compounds that could lower serum
      cholesterol or alter cell growth and differentiation.

PMID- 11339278
TI  - Utilization of the non-covalent fluorescent dye, NanoOrange, as a potential
      clinical diagnostic tool. Nanomolar human serum albumin quantitation.
AB  - The commercially available dye, NanoOrange, has been investigated as a potential
      tool for clinical diagnostics due to its low cost, ease of use, and ability to
      detect nanomolar concentrations of protein. Virtually non-fluorescent in dilute
      aqueous solutions, NanoOrange fluorescence is enhanced by at least an order of
      magnitude upon non-covalent interaction with proteins. These features, coupled
      with the requirement for high throughput assays in the clinical laboratory has
      prompted the development of two orthogonal NanoOrange approaches. Human serum
      albumin (HSA) was used as a model protein for the development of both 96-well
      microplate and capillary electrophoresis laser-induced fluorescence (CE-LIF)
      assay formats. Dye performance in five commonly used buffers of various
      concentrations and pH indicated considerable flexibility in assay buffer
      selection, with optimal performance at pH 9.0. A salt concentration study
      indicated that increasing NaCl concentration generally decreases fluorescence
      emission and can be minimized by pre-diluting biological samples to a final salt
      concentration of 20-80 mM. Titration of protein with NanoOrange resulted in
      optimal HSA-NanoOrange complex formation utilizing 1 x and 2 x NanoOrange in the
      96-well microplate and CE-LIF approaches, respectively. A NanoOrange binding
      model based on rapid signal enhancement and zero order fluorescence emission
      kinetics is proposed. The utilization of NanoOrange in CE-LIF based human serum
      analysis results in a signal-to-background ratio improvement of up to two orders
      of magnitude.

PMID- 11339277
TI  - Determination of isoprostaglandin F2alpha type III in human urine by gas
      chromatography-electronic impact mass spectrometry. Comparison with enzyme
      immunoassay.
AB  - F2-Isoprostanes are stable lipid peroxidation products of arachidonic acid, the
      quantification of which provides an index of oxidative stress in vivo. We
      describe a method for analysing isoprostaglandin F2alpha type III (15-F2t-IsoP)
      in biological fluids. The method involves solid-phase extraction on octadecyl
      endcapped and aminopropyl cartridges. After conversion to trimethylsilyl ester
      trimethylsilyl ether derivatives, isoprostaglandin F2alpha type III is analysed
      by mass spectrometry, operated in electronic impact selected ion monitoring mode.
      We have compared enzyme immunoassay (EIA; Cayman, Ann Arbor, MI, USA) to this
      method with 30 human urine aliquots following the same extraction procedure in
      order to determine the agreement between both methods. Isoprostaglandin F2alpha
      type III concentrations determined with gas chromatography-mass spectrometry (GC
      MS) did not agree with those determined with EIA. Our results suggest that GC-MS
      and EIA do not measure the same compounds. As a consequence, comparison of
      clinical results using GC-MS and EIA should be avoided.

PMID- 11339279
TI  - Peptide repertoire of human cerebrospinal fluid: novel proteolytic fragments of
      neuroendocrine proteins.
AB  - Polypeptides in human cerebrospinal fluid (CSF), isolated by phase separation in
      chloroform-methanol-water and reversed-phase HPLC, were characterised by sequence
      analysis and mass spectrometry. This identified the presence of peptide fragments
      of testican, neuroendocrine specific protein VGF, neuroendocrine protein 7B2,
      chromogranin B/secretogranin I, chromogranin A, osteopontin, IGF-II E-peptide and
      proenkephalin. The majority of these fragments were generated by proteolysis at
      dibasic sites, suggesting that they are derived by activities related to
      prohormone convertase(s). Several of the fragments have previously not been
      detected, and their functions in CSF or elsewhere are unknown. A characteristic
      feature of all these fragments is a very high content of acidic residues, in
      particular glutamic acid. In addition to the fragments of neuroendocrine
      proteins, endothelin-binding receptor-like protein 2, ribonuclease 1, IGF-binding
      protein 6, albumin, alpha1-acid glycoprotein 1, prostaglandin-H2 D-isomerase,
      apolipoprotein A1, transthyretin, beta2-microglobulin, ubiquitin, fibrinopeptide
      A, and C4A anaphylatoxin were found.

PMID- 11339280
TI  - Improved method for the measurement of large neutral amino acids in biological
      matrices.
AB  - A high-performance liquid chromatographic method for measuring neutral amino
      acids in rat sera, brain tissues, and perfusates was developed by using o
      phthalaldehyde sulfite as a pre-column derivatization reagent. With the present
      method, it was possible to separate the neutral amino acids within a single run
      in 25 min, while the acidic amino acids were eluted near or at the solvent front.
      The recovery was above 88.8% with a relative standard deviation (RSD) below 4.2%.
      The within- and between-day assay reproducibility for the determination of rat
      serum amino acids showed RSDs below 1.35 and 7.61%, respectively. In the present
      study, the neutral amino acids were assayed with high sensitivity, accuracy and
      good reproducibility in a relatively short time and on a small sample size.

PMID- 11339281
TI  - High-performance liquid chromatographic determination of cefepime in human plasma
      and in urine and dialysis fluid using a column-switching technique.
AB  - A high-performance liquid chromatographic method with UV absorbance was developed
      for the analysis of cefepime in human plasma and urine, and in dialysis fluid.
      Detection was performed at 280 nm. The assay procedure for cefepime in plasma
      involves the addition of an internal standard (cefpirome) followed by treatment
      of the samples with trichloracetic acid, acetonitrile and dichloromethane. To
      quantify cefepime in diluted urine (1:20) and in the dialysis fluid, samples
      spiked with the internal standard (cefpirome) were analysed using a column
      switching technique. The HPLC column, Nucleosil C18, was equilibrated with an
      eluent mixture composed of acetonitrile-ammonium acetate (pH 4). Linear detector
      responses were observed for the calibration curve standards in the range 0.5 to
      100 microg/ml, which spans what is currently thought to be the clinically
      relevant range for cefepime concentrations in body fluids. The limit of
      quantification was 0.5 microg/ml in the three matrices. Extraction recoveries
      proved to be more than 84%. Precision, expressed as %RSD, was in the range 1.5 to
      9%. Accuracy ranged from 93 to 105%. This method was used to follow the time
      course of the concentration of cefepime in plasma, urine and dialysate outlet
      samples after a 10-min infusion period of 2 g of this drug in patients with acute
      renal failure undergoing hemodiafiltration.

PMID- 11339282
TI  - Novel liquid chromatographic-tandem mass spectrometric methods using silica
      columns and aqueous-organic mobile phases for quantitative analysis of polar
      ionic analytes in biological fluids.
AB  - Use of silica stationary phase and aqueous-organic mobile phases could
      significantly enhance LC-MS-MS method sensitivity. The LC conditions were
      compatible with MS detection. Analytes with basic functional groups were eluted
      with acidic mobile phases and detected by MS in the positive ion mode. Analytes
      with acid functional groups were eluted with mobile phases at neutral pH and
      detected by MS in the negative ion mode. Analytes poorly retained on reversed
      phase columns showed good retention on silica columns. Compared with reversed
      phase LC-MS-MS, 5-8-fold sensitivity increases were observed for basic polar
      ionic compounds when using silica columns and aqueous-organic mobile phase. Up to
      a 20-fold sensitivity increase was observed for acidic polar ionic compounds.
      Silica columns and aqueous-organic mobile phases were used for assaying nicotine,
      cotinine, and albuterol in biological fluids.

PMID- 11339283
TI  - Validated gas chromatographic-mass spectrometric assay for determination of the
      antifreezes ethylene glycol and diethylene glycol in human plasma after microwave
      assisted pivalylation.
AB  - A gas chromatographic-mass spectrometric assay is described for identification
      and quantification of the antifreezes ethylene glycol (EG) and diethylene glycol
      (DEG) in plasma for early diagnosis of a glycol intoxication. After addition of
      1,3-propanediol as internal standard, the plasma sample was deproteinized by
      acetone and an aliquot of the supernatant was evaporated followed by microwave
      assisted pivalylation. After gas chromatographic separation, the glycols were
      first identified by comparison of the full mass spectra with reference spectra
      and then quantified. The quantification has been validated according to the
      criteria established by the Journal of Chromatography B. The assay was found to
      be selective. The calibration curves for EG and DEG were linear from 0.1 g/l to
      1.0 g/l. The limit of detection for EG and DEG was 0.01 g/l and the limit of
      quantification for both was 0.1 g/l. The absolute recoveries were 50 and 65% for
      the low quality control samples and 51 and 73% for the high quality control
      samples of EG and DEG, respectively. Intra- and inter-day accuracy and precision
      were inside the required limits. The glycols in frozen plasma samples were stable
      for more than 6 months. The method was successfully applied to several authentic
      plasma samples from patients intoxicated with glycols. It has also been suitable
      for analysis of EG and DEG in urine.

PMID- 11339284
TI  - Analysis of the metabolites of the sodium salt of 6-hydroxy-5-(phenylazo)-2
      naphthalenesulfonic acid in Sprague-Dawley rat urine.
AB  - The sodium salt of 6-hydroxy-5-(phenylazo)-2-naphthalenesulfonic acid (SS-AN),
      which is a subsidiary color present in Food Yellow No. 5 [Sunset Yellow FCF,
      disodium salt of 6-hydroxy-5-(4-sulfophenylazo)-2-naphthalenesulfonic acid], was
      orally administered to Sprague-Dawley rats. Metabolite A, metabolite B, and
      unaltered SS-AN were detected as colored metabolites in the rat urine. Analysis
      of the chemical structures showed that metabolite A (major peak) was 6-hydroxy-5
      (4-sulfooxyphenylazo)-2-naphthalenesulfonic acid, the sulfuric acid conjugate of
      SS-AN, and metabolite B (minor peak) was 6-hydroxy-5-(4-hydroxyphenylazo)-2
      naphthalenesulfonic acid (SS-PAP), which is a derivative of metabolite A without
      the sulfuric acid. The colorless metabolites p-aminophenol, o-aminophenol, and
      aniline present in the urine were analyzed by liquid chromatography-mass
      spectrometry. The orally administered SS-AN had been metabolized to the colorless
      metabolites (p-aminophenol 45.3%, o-aminophenol 9.4%, aniline 0.4%) in the 24-h
      urine samples. Analysis of the colored metabolites by high-performance liquid
      chromatography with detection at 482 nm indicated the presence of metabolite A
      (0.29%), SS-PAP (0.01%), and SS-AN (0.02%) were detected in the 24-h urine
      samples. Approximately 56% of SS-AN was excreted into the urine and the rest is
      probably excreted into feces.

PMID- 11339285
TI  - Solvent and solid-phase extraction of natural and synthetic anabolic steroids in
      human urine.
AB  - Liquid-liquid (using dichloromethane) and liquid-solid extraction processes
      (using disposable C18 cartridges) were applied to human urine samples spiked with
      15 androgenic anabolic steroids (natural and synthetic). The extraction
      recoveries were assessed from different HPLC separations of anabolic steroids
      using water-acetonitrile mobile phase, and using calibration graphs obtained by
      injection into HPLC of standard samples of these compounds before and after
      extraction. The procedures, including sample preconcentration, showed extraction
      efficiencies over 90% which were independent on a wide range of concentrations
      tested. Solid phase extraction yielded poor results for oximetolone, danazol and
      dehydroepiandrosterone. For real urine samples, hydrolysis using beta
      glucuronidase and washing using sodium hydroxide before and after solvent
      extraction, respectively, is recommended.

PMID- 11339286
TI  - Affinity purification of novel bispecific antibodies recognising carcinoembryonic
      antigen and doxorubicin.
AB  - We have developed a method which combines Protein A affinity chromatography and
      HPLC analytical and semipreparative hydroxyapatite affinity chromatography to
      purify bispecific antibodies (BsMabs) from hybrid-hybridomas secreting antibodies
      recognising carcinoembryonic antigen (CEA) and the chemotherapeutic drug
      doxorubicin (Dox). Elution of the HPLC hydroxyapatite columns with a 60-360 mM
      phosphate buffer gradient was found to give better separation than elution with a
      60-180 mM phosphate buffer gradient. Careful monitoring of HPLC fractions by
      enzyme linked immunosorbent assays for anti-CEA, anti-Dox and dual anti-CEA/anti
      Dox activity, and pooling of fractions on the basis of these results, enabled the
      purification of novel BsMabs for use in in vitro and preclinical in vivo
      experiments.

PMID- 11339287
TI  - Major human plasma lipid classes determined by quantitative high-performance
      liquid chromatography, their variation and associations with phospholipid fatty
      acids.
AB  - An HPLC method with evaporative light-scattering detection (ELSD) was optimized
      and validated for the simultaneous quantitation of cholesteryl esters (CEs),
      triacylglycerols (TGs), free cholesterol (FC) and phosphatidylcholine (PC) in
      human plasma. The separation of CEs from TGs, the most variable plasma lipid
      class, was improved by speeding up the gradient steps and by increasing the re
      equilibration time between runs. The calibrations were made at levels of 0.14-14
      microg lipid/injection. The intra- and inter-day precision values of the method
      ranged between 1.9 and 4.5 and 2.3-7.2% (RSD, n=6), respectively, including
      determinations at two concentration levels. In comparison to other lipid classes,
      quantitation of PC proved to be equally repeatable despite its lowest detector
      response. The relative recoveries varied from 97.0 to 110.3%, showing good
      accuracy of the method. The methodological variation of the lipid classes covered
      0.6-3.1% of their total variation in the study population (n=48). The CE/FC ratio
      showed an even closer relationship with phospholipid linoleic acid (18:2n-6;
      r=0.65, P<0.001) than with serum cholesterol levels, while eicosapentaenoic acid
      (20:5n-3) was significantly associated with PC (r=0.41, P<0.01). The CE/FC ratio
      increased (P<0.01) during soyabean oil substitution and the level of PC increased
      (P<0.01) during cold-pressed rapeseed oil substitution.

PMID- 11339288
TI  - Simultaneous determination of buprenorphine, norbuprenorphine, and buprenorphine
      glucuronide in plasma by liquid chromatography-tandem mass spectrometry.
AB  - For the first time, an LC-MS-MS method has been developed for the simultaneous
      analysis of buprenorphine (BUP), norbuprenorphine (NBUP), and buprenorphine
      glucuronide (BUPG) in plasma. Analytes were isolated from plasma by C18 SPE and
      separated by gradient RP-LC. Electrospray ionization and MS-MS analyses were
      carried out using a PE-Sciex API-3000 tandem mass spectrometer. The m/z 644-->m/z
      468 transition was monitored for BUPG, whereas for BUP, BUP-d4, NBUP, and NBUP-d3
      it was necessary to monitor the surviving parent ions in order to achieve the
      required sensitivity. The method exhibited good linearity from 0.1 to 50 ng/ml
      (r2> or =0.998). Extraction recovery was higher than 77% for BUPG and higher than
      88% for both BUP and NBUP. The LOQ was established at 0.1 ng/ml for the three
      analytes. The method was validated on plasma samples collected in a controlled
      intravenous and sublingual buprenorphine administration study. Norbuprenorphine
      glucuronide was also tentatively detected in plasma by monitoring the m/z 590-
      >m/z 414 transition.

PMID- 11339289
TI  - Determination of growth hormone-releasing hexapeptide by reversed-phase high
      performance liquid chromatography with electrochemical detection.
AB  - A novel HPLC method with electrochemical detection is described for the
      determination of a growth-hormone-releasing hexapeptide (GHRP-6). HPLC
      conditions, such as the column, mobile phase, and oxidation potential, were
      optimized for sensitivity and selectivity of analysis. GHRP-6 was separated on a
      reversed-phase CN column with 37% acetonitrile in 100 mM phosphate buffer (pH
      7.0) as the mobile phase. The optimum electrochemical oxidation signal was
      obtained at 0.85 V vs. Ag/AgCl in a glassy carbon working electrode due to two
      electroactive tryptophans and a histidine residue. Solid-phase extraction using
      octadecyl cartridges was optimized for sample cleanup of GHRP-6 from serum
      samples and the method was successfully applied over the concentration range of 5
      to 100 ng/ml of analyte. reserved.

PMID- 11339290
TI  - Application of a high-performance liquid chromatographic assay for the
      neuromuscular blocker gallamine to analysis of rat plasma, muscle and
      microdialysate samples.
AB  - A reliable high-performance liquid chromatographic method has been validated for
      determination of gallamine in rat plasma, muscle tissue and microdialysate
      samples. A C18 reversed-phase column with mobile phase of methanol and water
      containing 12.5 mM tetrabutyl ammonium (TBA) hydrogen sulphate (22:78, v/v) was
      used. The flow-rate was 1 ml/min with UV detection at 229 nm. Sample preparation
      involved protein precipitation with acetonitrile for plasma and muscle tissue
      homogenate samples. Microdialysate samples were injected into the HPLC system
      without any sample preparation. Intra-day and inter-day accuracy and precision of
      the assay were <13%. The limit of quantification was 1 microg/ml for plasma, 1.6
      microg/g for muscle tissue and 0.5 microg/ml for microdialysate samples. The
      assay was applied successfully to analysis of samples obtained from a
      pharmacokinetic study in rats using the microdialysis technique.

PMID- 11339291
TI  - Ion interaction reagent reversed-phase high-performance liquid chromatography
      determination of anti-tuberculosis drugs and metabolites in biological fluids.
AB  - New methods of ion interaction reagent (IIR) RP-HPLC are presented for the
      determination of anti-tuberculosis drugs and their metabolites, singly or in
      multi-component mixtures, in biological fluids. The following analytes are
      considered: isoniazid, ethionamide, pyrazinamide, morphazinamide, p
      aminosalicylic acid, nicotinic and isonicotinic acids. Aqueous solutions of three
      different ion interaction reagents are alternatively or comparatively used as the
      mobile phases, namely: (A) 5.00 mM octylamine at pH 3.00 for o-phosphoric acid,
      (B) 5.00 mM octylamine at pH 8.00 for o-phosphoric acid, and (C) 5.00 mM 1,6
      diaminohexane at pH 6.00 for o-phosphoric acid. The response linearity between
      peak area and analyte concentration is verified for all the analytes in the
      concentration range within the determination limits and 2.00 mg/l. Detection
      limits are always lower than 82 microg/l for standard solutions; in the analysis
      of samples of rat serum, rat plasma and human serum, the matrix effect is
      negligible, the detection limits are always lower than 94 microg/l and the
      average recovery yield is always greater than 96%.

PMID- 11339292
TI  - Assay of omeprazole and omeprazole sulfone by semi-microcolumn liquid
      chromatography with mixed-function precolumn.
AB  - A column-switching system based on semi-microcolumns was used for direct analysis
      of omeprazole and omeprazole sulfone in human plasma samples. Plasma samples were
      injected into a mixed-function (MF Ph-1) column (35 mmx4.6 mm I.D.) to remove
      proteins and other non-specific peak producing substances from the analyte
      containing time zone. The analyte-containing fraction was thereafter transferred
      to a C-18 semi-microcolumn (250 mmx1.5 mm I.D.) after concentration at the C-18
      intermediate column. The absorbance at 302 nm in a ultraviolet (UV) detector was
      recorded to measure the concentration. The detection limit for omeprazole and
      omeprazole sulfone in the present method was 10 ng/ml. Interbatch variation
      (coefficient of variation) of the QC samples spanned less than 10% and intra
      batch variation less than 2%. The recovery ratios of omeprazole and omeprazole
      sulfone were over 98%. The current method can be used as a simpler procedure with
      similar sensitivity and reproducibility as previously reported methods.

PMID- 11339293
TI  - Measurement of testosterone and pregnenolone in nails using gas chromatography
      mass spectrometry.
AB  - An efficient method for the determination of testosterone and pregnenolone in
      human nails using gas chromatography-mass spectrometry (GC-MS) with d3
      testosterone as an internal standard is described. The method involves alkaline
      digestion and liquid-liquid extraction, with subsequent conversion to mixed
      pentafluoropenyldimethylsilyl-trimethylsilyl (flophemesyl-TMS) derivatives for
      sensitive analysis in the selected-ion monitoring (SIM) mode. The limit of
      detection (LOD) and limit of quantification (LOQ) were lowered to 0.1 and 0.2
      pg/g, respectively, when 100 mg of nail-clippings were used. The mean recoveries
      of testosterone and pregnenolone were 89.8 and 86.7%, respectively, while good
      overall precision (% C.V.; 4.5-9.5) and accuracy (% bias; 3.9-8.4) were
      demonstrated. Linearity as a correlation coefficient was 0.9913 (testosterone)
      and 0.9965 (pregnenolone). When applied to fingernail and toenail samples from
      seven healthy men and nine healthy women, testosterone and pregnenolone were
      positively detected in the concentration range of 0.24-5.80 ng/g. The levels of
      two steroids studied in the nails were found to be higher in the male subjects
      than in the female subjects, and except for the toenails of the females, the
      levels of testosterone were higher than those of pregnenolone.

PMID- 11339294
TI  - Chromatographic method for the determination of diazepam, pyridostigmine bromide,
      and their metabolites in rat plasma and urine.
AB  - This study describes a chromatographic method for the determination of diazepam,
      an anxiolytic drug that is also used as an antidote against nerve agent seizures,
      its metabolites N-desmethyldiazepam, and temazepam, the anti-nerve agent drug
      pyridostigmine bromide (PB; 3-dimethylaminocarbonyloxy-N-methyl pyridinium
      bromide) and its metabolite N-methyl-3-hydroxypyridinium bromide in rat plasma
      and urine. The compounds were extracted using C18 Sep-Pak Vac 3cc (500 mg)
      cartridges and separated using isocratic mobile phase of methanol, acetonitrile
      and water (pH 3.2) (10:40:50) at a flow-rate of 0.5 ml/min in a period of 12 min,
      and UV detection ranging between 240 and 280 nm. The limits of detection for all
      analytes ranged between 20 and 50 ng/ml, while limits of quantitation were 100
      ng/ml. Average percentage extraction recoveries of five spiked plasma samples
      were 79.1+/-7.7, 83.5+/-6.4, 83.9+/-5.9, 71.3+/-6.0 and 77.7+/-5.6, and from
      urine 79.4+/-7.9, 83.1+/-6.9, 73.6+/-7.7, 74.3+/-7.1 and 77.6+/-5.9 for diazepam,
      N-desmethyldiazepam, temazepam, pyridostigmine bromide, and N-methyl-3
      hydroxypyridinium bromide, respectively. The relationship between peak areas and
      concentration was linear over the range between 100 and 1000 ng/ml. This method
      was applied to determine the above analytes following a single oral
      administration in rats as a tool to study the pharmacokinetic profile of each
      compound, alone and in combination.

PMID- 11339295
TI  - High-performance liquid chromatographic determination of sphinganine and
      sphingosine in serum and urine of subjects from an endemic nephropathy area in
      Croatia.
AB  - Endemic nephropathy (EN) is a chronic renal disease present as an endemic in
      Brodska Posavina, Croatia. The aim of the study was to assess the possible role
      of fumonisins, i.e., mycotoxins produced by Fusarium moniliforme, as causative
      agents for EN. Fumonisins inhibit ceramide synthase, the enzyme of de novo
      synthesis of sphingolipids, which leads to an increase in the
      sphinganine/sphingosine ratio. In the present study, a modified method has been
      used for the determination of the sphinganine/sphingosine ratio in human serum
      and urine of healthy subjects and EN patients from the endemic area. Free
      sphingoid bases, sphinganine and sphingosine, were obtained by base hydrolysis.
      Afterwards, precolumn ortho-phthaldialdehyde derivatisation, HPLC separation and
      quantification by fluorescence detection were performed. The results thus
      obtained pointed to a sphingolipid metabolism impairment, which may have been
      induced by fumonisins or fumonisin-like mycotoxins. As statistically significant
      differences were recorded in the subjects not yet affected with EN, an impairment
      in the metabolism of sphingolipids might be considered as an early indicator of
      EN.

PMID- 11339296
TI  - Thiophilic interaction chromatography of prostate-specific antigen.
AB  - Prostate-specific antigen (PSA) protein and complexes of PSA with alpha1
      antichymotrypsin (PSA-ACT) or alpha2-macroglobulin (PSA-A2M) prepared in vitro,
      have strong affinity for different thiophilic gels (T-gel). Free PSA, and these
      PSA complexes can be isolated due to their affinity for T-gels. The average
      recovery of PSA from several of the T-gels, based upon ELISA measurements, was 84
      to 94%. The data suggest that T-gel affinity can be explored for the purification
      of free and complexed PSA from various biologic fluids.

PMID- 11339297
TI  - Expedient liquid chromatographic method with fluorescence detection for
      montelukast sodium in micro-samples of plasma.
AB  - This study describes an expedient assay for the analysis of the asthma
      medication, montelukast sodium (Singulair, MK-0476), in human plasma samples.
      After a simple extraction of the plasma, the drug and internal standard, quinine
      bisulfate, were measured by HPLC. The chromatographic system consisted of a
      single pump, a refrigerated autosampler, a C8 4-microm particle size radial
      compression cartridge at 40 degrees C and a fluorescence detector with the
      excitation and emission wavelengths set at 350 and 400 nm, respectively. The
      mobile phase which was delivered at 1.0 ml/min, was prepared by adding 200 ml of
      0.025 M sodium acetate, pH adjusted to 4.0 with acetic acid, to 800 ml of
      acetonitrile, with 50 microl triethylamine. With a run time of only 10 min per
      sample, this assay had an overall recovery of >97% with a detection limit of 1
      ng/ml. The inter- and intra-run relative standard deviations at 0.05, 0.2 and 1.0
      microg/ml were all <9.2%, while the analytical recovery at the same
      concentrations were within 7.7% of the amount added.

PMID- 11339299
TI  - A study of a new TSM bio-mimetic sensor using a molecularly imprinted polymer
      coating and its application for the determination of nicotine in human serum and
      urine.
AB  - A new bio-mimetic quartz crystal thickness-shear-mode (TSM) sensor, using an
      imprinted polymer coating as the sensitive material, has been fabricated and
      applied to the determination of nicotine (NIC) in human serum and urine. The
      molecularly imprinted polymer (MIP) was synthesized using NIC as the template
      molecule and methacrylic acid (MAA) as the functional monomer. The sensor showed
      high selectivity and a sensitive response to NIC in aqueous system. The linear
      response range of the sensor was between 5.0 x 10(-8) and 1.0 x 10(-4) M with a
      detection limit of 2.5 x 10(-8) M. The viscoelasticity of the coating in the air
      and in liquid has been studied by the impedance spectrum. The MIP sensor was
      stable and exhibited effective reproducibility. Satisfactory results were
      achieved in the detection of the real samples.

PMID- 11339298
TI  - Development of a high-performance liquid chromatographic method for the
      quantification of chlorpyrifos, pyridostigmine bromide, N,N-diethyl-m-toluamide
      and their metabolites in rat plasma and urine.
AB  - A method was developed for the separation and quantification of the insecticide
      chlorpyrifos (O,O-diethyl-O[3,5,6-trichloro-2-pyridinyl] phosphorothioate), its
      metabolites chlorpyrifos-oxon (O,O-diethyl-O[3,5,6-trichloro-2-pyridinyl]
      phosphate) and TCP (3,5,6-trichloro-2-pyridinol), the anti-nerve agent drug
      pyridostigmine bromide (PB; 3-dimethylaminocarbonyloxy-N-methyl pyridinium
      bromide), its metabolite N-methyl-3-hydroxypyridinium bromide, the insect
      repellent DEET (N,N-diethyl-m-toluamide), and its metabolites m-toluamide and m
      toluic acid in rat plasma and urine. The method is based on using solid-phase
      extraction and high-performance liquid chromatography (HPLC) with reversed-phase
      C18 column, and gradient UV detection ranging between 210 and 280 nm. The
      compounds were separated using a gradient of 1-85% acetonitrile in water (pH
      3.20) at a flow-rate ranging between 1 and 1.7 ml/min over a period of 15 min.
      The retention times ranged from 5.4 to 13.2 min. The limits of detection ranged
      between 20 and 150 ng/ml, while the limits of quantitation were between 150 and
      200 ng/ml. Average percentage recovery of five spiked plasma samples was 80.2+/
      7.9, 74.9+/-8.5, 81.7+/-6.9, 73.1+/-7.8, 74.3+/-8.3, 80.8+/-6.6, 81.6+/-7.3 and
      81.4+/-6.5, and from urine 79.4+/-6.9, 77.8+/-8.4, 83.3+/-6.6, 72.8+/-9.0, 76.3+/
      7.7, 83.4+/-7.9, 81.6+/-7.9 and 81.8+/-6.8 for chlorpyrifos, chlorpyrifos-oxon,
      TCP, pyridostigmine bromide, N-methyl-3-hydroxypyridinium bromide, DEET, m
      toluamide and m-toluic acid, respectively. The relationship between peak areas
      and concentration was linear over a range between 200 and 2000 ng/ml.

PMID- 11339300
TI  - Drastic high magnetic field effect on suppression of Escherichia coli death.
AB  - When Escherichia coli B was aerobically grown in a medium containing one-fourth
      the concentration of the LB medium supplemented with glutamic acid at 43 degrees
      C under an inhomogeneous 5.2-6.1 T magnetic field, the number of cells in the
      stationary phase under the high magnetic field was 100,000 times higher than that
      under a geomagnetic field. The finding that the amount of sigma S factor encoded
      by the rpoS gene under the high magnetic field was larger than that under the
      control geomagnetic field indicated that the activity of the rpoS gene was
      affected by the high magnetic field.

PMID- 11339301
TI  - The passive DC conductivity of human tissues described by cells in solution.
AB  - The electrical conductivity of human tissue at low frequencies is discussed when
      a uniform electric field is applied to some tissue containing many cells. Human
      tissue is described as a suspension of particles in a conducting solution.
      Relations are derived for the apparent conductivity of a cell surrounded by a
      membrane. These relations can be used to estimate the accuracy of a model that
      considers the cell as a non-conducting particle. Usually, a tissue is composed of
      several types of particles. A relationship that expresses the effective
      conductivity of a suspension of one type of ellipsoidal particles could be found
      in the literature. The orientation of the particles could be uniform or they
      could be randomly distributed. For non-conducting particles, this expression is
      known as Archie's law. The expression is extended such that also the effective
      conductivity of a suspension of various types of particles can be calculated. The
      result is evaluated for the cortex of the brain using experimental data given in
      the literature.

PMID- 11339302
TI  - The influence of storage time on the temperature dependence of the dc electrical
      conductivity of horn keratin.
AB  - The direct current electrical conductivity of horn keratin was measured as a
      function of temperature, in the temperature range 290-480 K, with a constant
      heating rate, for samples stored for periods of 2-3 weeks and 5 months. The
      activation energy of charge conducting process was calculated. The longer storage
      time reduced the water content, and the electrical conductivity, but increased
      the activation energy at 290-320 K.

PMID- 11339303
TI  - Disappearance of growth advantage in stationary phase (GASP) phenomenon under a
      high magnetic field.
AB  - The phenomenon called growth advantage in stationary phase (GASP) originally
      discovered by Kolter et al. was confirmed using two bacterial strains,
      Escherichia coli ZK126Nalr and ZK126Smr, under the geomagnetic field. However,
      when the same experiment was conducted in an inhomogeneous high magnetic field of
      5.2-6.1 T, almost no death of ZK126Smr was observed and the GASP phenomenon
      disappeared. When the same experiment was conducted in a homogeneous magnetic
      field of 7 T, the GASP was significantly delayed due to the much slower death
      rate of ZK126Smr than that in the geomagnetic field. These data are consistent
      with our previous finding that a high magnetic field reduces the death rate of
      bacteria and enhances their survivability in a stationary phase.

PMID- 11339304
TI  - Optimal frequencies for magnetic acceleration of cytochrome oxidase and Na,K
      ATPase reactions.
AB  - Low frequency magnetic fields increase the activity of the membrane enzymes, Na,K
      ATPase and cytochrome oxidase, and the increased activity varies with frequency.
      Optimal frequencies for increases in the reaction rate constant of cytochrome
      oxidase and in the rate of splitting of ATP by Na,K-ATPase differ by an order of
      magnitude, and are in the ranges of the turnover numbers of the respective enzyme
      reactions. The two frequency dependence curves are similar in that the slope of
      the low frequency portion is about 10 times greater than the slope of the high
      frequency portion. The greater slope indicates greater ability to adjust quickly
      in the low frequency range, which may be significant for optimal biological
      control of activity.

PMID- 11339305
TI  - In situ infrared spectroelectrochemical studies on adsorption and oxidation of
      nucleic acids at glassy carbon electrode.
AB  - The adsorption and oxidation of yeast RNA and herring sperm DNA (HS DNA) at glass
      carbon (GC) electrode are studied by differential pulse voltammetry (DPV) and in
      situ FTIR spectroelectrochemistry. Two oxidation peaks of yeast RNA are obtained
      by DPV, whose peak potentials shift negatively with increasing pH. The peak
      currents decrease gradually in successive scans and no corresponding reduction
      peaks occur, thus indicating that the oxidation process of yeast RNA is
      completely irreversible. The IR bands in the 1200-1800 cm(-1) range, attributed
      to the stretching and ring vibrations of nucleic acid bases, show the main
      spectral changes when the potential is shifted positively, which gives evidence
      that the oxidation process takes place in the base residues. The oxidation
      process of HS DNA is similar to that of yeast RNA. The results both from DPV and
      in situ FTIR spectroelectrochemistry confirm that the guanine and adenine
      residues can be oxidized at the electrode surface, which is consistent with the
      oxidation mechanism of nucleic acids proposed previously.

PMID- 11339306
TI  - Electroanalytical applications of cationic self-assembled monolayers: square-wave
      voltammetric determination of dopamine and ascorbate.
AB  - Gold electrodes modified with cationic self-assembled monolayers (SAMs) of 2,2'
      dithiobisethaneamine (CYST) and 6,6'-dithiobishexaneamine (DTH) were used for the
      simultaneous determination of dopamine (DA) and ascorbate (AA). The cationic SAM
      modified electrodes have several advantages over the bare electrode for the
      oxidation of AA. A very large (approximately 450 mV) decrease in the
      overpotential for the oxidation of AA when compared with the bare electrode has
      been observed at the cationic monolayer-modified electrode. The electrostatic
      interaction of negatively charged AA with the monolayer shift the oxidation peak
      potential of AA to less positive potential and enhances the peak current. On the
      other hand, the positively charged DA is repelled from the monolayer and the
      oxidation potential shifts to more positive potential when compared to the bare
      electrode. The electrochemical oxidation of AA at the mixed monolayer of CYST and
      diethyl disulfide (DEDS) supports the influence of cationic terminal group of the
      monolayer on the oxidation of AA. Since the oxidation of AA occurs well before
      the oxidation potential of DA is reached, the homogeneous catalytic oxidation of
      AA by the oxidized DA has been advantageously eliminated at the monolayer
      modified electrode. The cationic self-assembled monolayers successfully detect DA
      in the presence of high concentration of AA. The sensitivity of the electrode
      modified with CYST monolayer was found to be 0.036 and 0.021 microA/microM
      towards AA and DA, respectively.

PMID- 11339307
TI  - Effects of radiation on frozen lactate dehydrogenase.
AB  - Results concerning the influence of 6-MeV electron beam irradiation, of 2.45-GHz,
      565-W microwaves, and of the combined electron and microwave irradiation, at -21
      degrees C and -196 degrees C, on lactate dehydrogenase activity are presented.
      The microwave-irradiated samples exhibited a non-linear behaviour (successive
      activation and inactivation of the enzyme molecules), suggesting the major
      influence of the non-thermal component of microwave radiation. The combined
      electron and microwave irradiation led to a decrease of activity similar to the
      one caused by electron beam irradiation, which seemed to prove that microwave
      influence was insignificant in the dose, power and time ranges used. The
      radiation target analysis of the enzymatic decrease due to electron irradiation
      indicated a very large aggregation of the enzyme molecules. Our data suggest that
      radiation target analysis is not suitable to measure the molecular mass of
      lactate dehydrogenase, when frozen enzyme suspensions are irradiated. The D2O
      protected enzyme, when exposed to electron irradiation, showed an even larger
      aggregation according to radiation target analysis, while the microwave
      irradiation of the protected enzyme led to a similar, though lesser, non-linear
      behaviour of the frozen enzyme molecules.

PMID- 11339308
TI  - Amperometric detection of DNA hybridization on a gold surface depends on the
      orientation of oligonucleotide chains.
AB  - We tested the possibility of amperometric detection of DNA hybridization on a
      gold surface influenced by the immobilization of oligonucleotide giving different
      orientations of single stranded DNA relative to the gold surface. The DNA sensor
      was fabricated by chemisorption of 18-mer oligonucleotide modified by a
      phosphorothioate group either at its 3' or both 3' and 5' terminal. After
      immobilization of oligonucleotide to the gold support, the sensor was immersed in
      11-mercaptoundecanoic acid (MUA) solution. Further chemisorption of MUA resulted
      in approximately 10-fold increase of resistance of the organic layer. Addition of
      complementary oligonucleotide resulted in an increase of conductivity for DNA
      sensor oriented perpendicular to the gold support (DNA with one thiol group),
      while the conductance decreased for DNA sensor with single stranded DNA oriented
      parallel to the gold support (with DNA modified by thiol groups at both 3' and 5'
      terminals). Addition of non-complementary chain resulted a slight decrease or no
      change of sensor conductivity. The hybridization process at both types of DNA
      orientations is not cooperative and can be described by Langmuir isotherms. The
      hybridization event on gold support has been confirmed by mass detection using
      the quartz crystal microbalance technique.

PMID- 11339309
TI  - Direct electrochemistry of hemoglobin in layer-by-layer films with poly(vinyl
      sulfonate) grown on pyrolytic graphite electrodes.
AB  - Stable layer-by-layer electroactive films were grown on pyrolytic graphite (PG)
      electrodes by alternate adsorption of layers of polyanionic poly(vinyl sulfonate)
      (PVS) and positively charged hemoglobin (Hb) from their aqueous solutions. Cyclic
      voltammetry (CV) of [PVS/Hb]n films showed a pair of well-defined and nearly
      reversible peaks at about - 0.28 V vs. SCE at pH 5.5, characteristic of Hb heme
      Fe(III)/Fe(II) redox couple. The process of (PVS/Hb) bilayer growth was monitored
      and confirmed by CV, X-ray photoelectron spectroscopy (XPS) and UV-Vis
      spectroscopy. While the amount of Hb adsorbed in each bilayer was the same, the
      amount of electroactive Hb in each bilayer decreased dramatically with increase
      of the number of bilayer, and electroactivity was just extended to 8 [PVS/Hb]
      bilayers. CVs of [PVS/Hb]8 films maintained stable in buffers containing no Hb.
      Positions of Soret band of Hb in [PVS/Hb]n films grown on transparent glass
      slides suggest that Hb in the films keeps its secondary structure similar to its
      native state in a wide pH range. Trichloroacetic acid and nitrite were
      catalytically reduced by [PVS/Hb]8 films with significant lowering of the
      electrode potential required.

PMID- 11339310
TI  - Mathematical modelling of physicochemical reactions and transport processes
      occurring around a platinum cathode during the electrochemical treatment of
      tumours.
AB  - The electrochemical treatment (EChT) of tumours is an anti-tumour therapy in
      which a continuous direct current is applied to electrodes, placed in or near a
      tumour. Promising results have been reported from clinical trials in China, where
      more than 10,000 patients have been treated with EChT during the past 10 years.
      Before clinical trials can be conducted outside of China, a reliable dose
      planning strategy has to be developed. One approach in achieving this is the use
      of physicochemical simulation models. A simplified mathematical model of the
      physicochemical processes, occurring around a spherical platinum cathode during
      EChT, is developed and visualized in three steps in this paper. In the final
      step, tissue is treated as an aqueous solution of sodium chloride, containing a
      bicarbonate buffer system and organic constituents susceptible to reactions with
      hydroxyl ions. This model is shown to give a good description of the pH profile
      obtained around the cathode after EChT. The simulation results reveal a strong
      correlation between the pH profiles and size of experimentally measured lesions,
      thus indicating that it is the spreading of hydroxyl ions that determines the
      extent of tissue destruction around the cathode. In addition, the simulations
      indicate that the model could be of use in predicting the size of a lesion
      produced by EChT.

PMID- 11339311
TI  - Comparative study on photosynthetic activity of chloroplasts in acid and alkaline
      zones of Chara corallina.
AB  - A novel experimental approach has been applied to investigate the relationship
      between pH banding in Chara cells and photosynthetic activity of chloroplasts
      located in cell regions adjacent to acid and alkaline bands. The combination of
      pH microelectrode technique with pulse amplitude modulation (PAM)
      microfluorimetry enabled parallel measurements of longitudinal pH profiles and
      chlorophyll fluorescence yield in acid and alkaline zones of individual Chara
      cells. The scanning with a pH-microelectrode along the cell length revealed the
      light-dependent pH pattern, i.e., alternating acid and alkaline bands with pH
      differences as large as 2 - 3 pH units. In parallel, measurements of chlorophyll
      fluorescence yield under actinic light were performed using PAM microfluorometry.
      It was found that the effective photochemical yield of photosystem II is
      substantially higher in acid than in alkaline zones. The results clearly show
      that the banding pattern is not confined solely to the plasmalemma but is also
      exhibited in alternating photosynthetic performance of the underlying chloroplast
      layer. Apparently, the acid regions enriched with CO2 ensure sufficient flow of
      this substrate to the Calvin cycle reactions, thus promoting the photosynthetic
      rate, whereas the alkaline zones devoid of CO2 favor radiative losses of absorbed
      solar energy in chloroplasts.

PMID- 11339312
TI  - Effect of D2O and cryosolvents on the redox properties of bacteriochlorophyll
      dimer and electron transfer processes in Rhodobacter sphaeroides reaction
      centers.
AB  - Effects of environmental changes on the reaction pattern of excitation energy
      trapping and transformation into the "stable" radical pair P+Q(A)-, have been
      analyzed in isolated reaction centers of the anoxygenic purple bacterium
      Rhodobacter sphaeroides. The following results were obtained: (a) replacement of
      exchangeable protons by deuterons significantly retarded the electron transfer
      steps of primary charge separation, leading to the radical pair P+I- and of the
      subsequent reoxidation of I- by the quinone acceptor Q(A) but has virtually no
      effect on the midpoint potential of P/P+ that was found to be 430+/-20 mV; (b)
      addition of 70% (v/v) glycerol causes a shift of Em by about 30 mV towards higher
      values whereas the kinetics of the electron transfer reactions remain almost
      unaffected; (c) in the presence of the cryoprotectant DMSO, a combined effect
      arises, i.e. a retardation of the electron transfer kinetics comparable to that
      induced by H/D exchange and simultaneously an upshift of the Em value to 475+/-20
      mV, resembling the action of glycerol. These results are discussed within the
      framework of effects on the midpoint potential due to the dielectric constant of
      the medium and changes of the charge distribution in the vicinity of the redox
      groups and the influence of relaxation processes on electron transfer reactions.

PMID- 11339313
TI  - Spectroelectrochemical study of cellobiose dehydrogenase and diaphorase in a
      thiol-modified gold capillary in the absence of mediators.
AB  - A spectroelectrochemical cell was constructed from a gold capillary with 200
      microm inner diameter as a working electrode. This allowed spectroelectrochemical
      study of liquid samples with available volumes less than 5 microl. The optical
      measurements were accomplished with an optical fibre spectrometer. The optical
      path of the cell was about 1 cm. To facilitate electrochemistry of biomolecules,
      the surface of the gold capillary was modified with thiols. The formal potential,
      E degrees', of the heme in cellobiose dehydrogenase (CDH) from Phanerochaete
      chrysosporium was determined by spectroelectrochemistry in the absence of redox
      mediators. The number of electrons per redox conversion of heme in CDH was found
      to be equal to 0.98 + 0.04 corresponding well to a theoretical value representing
      the redox reaction Fe3+ + e-= Fe2+. Similar spectroelectrochemical experiments
      with diaphorase from Bacillus stearothermophilus showed the redox conversion of
      the flavin mononucleotide in diaphorase in the absence of external redox
      mediators.

PMID- 11339314
TI  - Facilitated electrochemical oxidation of NADH and its model compound at gold
      electrode modified with terminally substituted electroinactive self-assembled
      monolayers.
AB  - The electrochemical oxidation of NADH and its model compound, N-benzyl-1,4
      dihydronicotinamide (DHN), has been studied at gold electrode modified with self
      assembled monolayer of terminally substituted thiols/disulfide, i.e., cystamine
      (CYST), mercaptopropionic acid (MPA) and mercaptoethanol (ME). A substantial
      decrease in the overpotential (approximately 250 mV) when compared to the bare
      electrode has been observed for the oxidation of NADH at the monolayer-modified
      electrodes, containing no so-called redox mediator. The bare electrode shows an
      ill-defined voltammetric peak for the oxidation of DHN, whereas the monolayer
      modified electrodes showed a well-defined voltammetric peak. The monolayer
      assembly on the gold electrode prevents the fouling of electrode surface by the
      oxidation products, which favors the oxidation at the less positive potential.
      The square-wave voltammograms showed a sharp voltammetric signal for the
      oxidation of NADH at all the monolayer-modified electrodes. All the monolayer
      modified electrodes showed a linear current response to change in the NADH
      concentration in its range of 25-300 microM and their sensitivities were found to
      be 0.005+/-0.0003, 0.0063+/-0.0002 and 0.0052+/-0.0003 microA/microM for CYST-Au,
      ME-Au and MPA-Au electrodes, respectively. The hydrodynamic voltammograms
      obtained at the rotating CYST-Au electrode for the oxidation of NADH and DHN were
      used to estimate the diffusion coefficient of DHN, and the number of electrons
      involved in the oxidation process of NADH.

PMID- 11339315
TI  - Genetic and environemental factors in conduct problems and adult antisocial
      behavior among adult female twins.
AB  - Most twin and adoption studies of conduct problems have demonstrated modest
      genetic effects but substantial contributions of shared family environment.
      Conversely, most investigations have shown marked genetic influences but modest
      contributions of shared family environment in adult antisocial behavior. However,
      most previous work has focused on male subjects. We obtained retrospective
      reports of DSM-III-R-defined conduct disorder (CD) and adult antisocial behaviors
      from a population-based sample of female-female twin pairs. Genetic and
      environmental contributions to conduct problems and adult antisocial behaviors
      were examined using polychoric correlation coefficients and univariate structural
      equation modeling. Statistically significant but modest heritability was observed
      for conduct problems. A small, statistically nonsignificant contribution of
      shared family environment to CD behavior was also noted. Adult antisocial
      symptoms showed modest contributions of both additive genetic and shared family
      environmental factors. In both childhood and adulthood, the largest influence on
      antisocial behavior was individual-specific environment. Our findings support the
      importance of both genetic and environmental factors in antisocial behavior among
      women as well as the possibility that the relative importance of each set of
      influences differs by sex in both childhood and adulthood.

PMID- 11339316
TI  - Death ideation and its correlates: survey of an over-65-year-old population.
AB  - The presence of dissatisfaction with life or thoughts of death or suicide has
      been variously surveyed in adolescent samples and in the general population, but
      there is a paucity of research on the elderly. The aim of this study was to
      assess, in an elderly community-dwelling population: a) the prevalence of death
      and/or suicidal feelings and thoughts and any attempted suicides; and b) factors
      associated with these experiences. A total of 611 over-65-year-old subjects were
      interviewed at home. Seventeen percent of the total (F:M = almost 2:1) responded
      affirmatively to at least one of the questions on suicidality. Elderly people
      reporting suicidal feelings presented markedly higher levels of physical and
      psychological distress, such as depression, anxiety, and hostility. Results
      indirectly confirm that depressive symptomatology is not adequately treated.
      Greater attention is warranted in psychological evaluation of the elderly to take
      into account those risk factors that, if identified and managed, could reduce the
      frequency of suicidal thoughts and, probably, associated actions.

PMID- 11339317
TI  - Gilles de la Tourette's syndrome with and without obsessive-compulsive disorder
      compared with obsessive-compulsive disorder without tics: which symptoms
      discriminate?
AB  - Stereotyped repetitive behaviors occur in Gilles de la Tourette's Syndrome (GTS)
      and obsessive-compulsive disorder (OCD). The present study was undertaken to
      compare the distribution of obsessive-compulsive and Tourette-related impulsive
      behaviors in GTS with (+) OCD, GTS without (-) OCD, tic-free OCD, and control
      subjects. Fourteen GTS + OCD, 18 GTS-OCD, 21 OCD-tic, and 29 control subjects
      were evaluated using a semistructured interview designed to assess GTS and OCD
      related repetitive behaviors. Each reported item was evaluated on the presence of
      anxiety and goal-directedness. This information was subsequently used to define
      whether the repetitive behavior was an (anxiety-related) obsession or compulsion,
      or a (non-anxiety-related) OC-like behavior, impulsion. GTS + OCD subjects
      reported more overall Tourette-related impulsions than OCD-tic subjects, i.e.,
      more mental play, echophenomena, and touching behaviors but similar frequencies
      of typical obsessive-compulsive behaviors. Further, GTS + OCD subjects exhibited
      more overall repetitive behaviors than GTS-OCD subjects, i.e., more Tourette
      related impulsions as well as more obsessive-compulsive behaviors. The
      distribution of symptoms is similar in GTS with and without OCD, and differs from
      tic-free OCD. These differences suggest that GTS with OCD constitutes a form of
      GTS, not of OCD, although the possibility that GTS + OCD patients constitute a
      subgroup distinct from GTS and from OCD can not be excluded by this
      phenomenological study. Specific non-anxiety-related impulsions seem to
      discriminate between GTS and OCD-tic individuals. These impulsions possibly
      reflect differences in underlying mechanisms between GTS and OCD-tics.

PMID- 11339318
TI  - Hospital-based adolescent substance abuse treatment: comorbidity, outcomes, and
      gender.
AB  - Positive change was demonstrated on a number of self-report scales administered
      to 129 adolescents at a hospital-based substance abuse program, of whom 72 were
      posttested after 8 weeks. Female subjects showed change on more measures than
      male subjects, and a greater number of female subjects went from the clinical to
      subclinical range. Based on number of sessions attended, subjects were grouped by
      "dose" into either "hi-attenders" or "lo-attenders." A Trials (pretest/posttest)
      x Dose interaction revealed significant reduction in drug use at posttest for hi
      attenders who were initially heavier users. Multiple regression analyses
      determined how well "comorbidity" predicted attendance and change in drug use.
      Although comorbidity failed to predict attendance consistently, male subjects who
      reported more internalizing symptomatology reduced their drug use to a greater
      extent than those low on this dimension, and female subjects who initially
      reported experiencing more family problems became more self-efficacious about
      future drug avoidance.

PMID- 11339319
TI  - Cross-cultural validity and reliability testing of a standard psychiatric
      assessment instrument without a gold standard.
AB  - The objective of this study was to assess the cross-culture validity and
      reliability of a standard psychiatric assessment instrument without the usual
      "gold standards." Normally criterion validity testing requires comparison with
      such a standard--usually another instrument or a professional diagnosis. Instead
      local informants identified persons with and without "agahinda gakabije" (a
      locally described grief syndrome) who were then asked if they thought they had
      this syndrome and also interviewed using the depression section of the Hopkins
      Symptom Checklist (DHSCL). To assess criterion validity, interviews where
      respondent and informant agreed on the presence or absence of agahinda gakabije
      were compared with depression diagnosis using the DHSCL. We also assessed
      construct validity (using factor analysis), internal reliability (Cronbach's
      alpha), and test-retest reliability using results from a subsequent community
      based survey employing the DHSCL. We found a similar relationship between
      depression and agahinda gakabije as between depression and grief in western
      countries, which supports criterion validity. Construct validity and internal
      reliability were good (Cronbach's alpha = 0.87). Test-retest reliability of a
      DHSCL-based scale was less adequate (0.67). Although not replacing the usual gold
      standards for testing criterion validity, this approach may prove useful where
      these standards are unavailable. As this includes much of the developing world,
      this could result in more accurate mental health assessments among populations
      for whom this has hitherto not been possible.

PMID- 11339320
TI  - Local perceptions of the mental health effects of the Rwandan genocide.
AB  - The objectives of this study were to investigate how Rwandans perceive the mental
      health effects of the 1994 genocide, to investigate the local validity of western
      mental illness concepts, and (if these concepts were found to be valid) to
      provide data to adapt existing mental health assessment instruments for local
      use. We used three ethnographic methods to interview people in two rural areas in
      Rwanda: first, free listing provided a list of local terms for mental symptoms
      and disorders; second, key informant interviews then provided more detailed
      information about these disorders; and finally, pile sorts confirmed the
      relationships among symptoms and disorders that emerged from the other methods.
      We found that interviewees described the diagnostic symptoms of depression and
      posttraumatic stress disorder as results of the genocide and also described
      associated "local" symptoms not included in the established diagnostic criteria.
      They divided symptoms into a "mental trauma" syndrome that included the
      posttraumatic stress disorder symptoms and some depression and local symptoms,
      and a grief syndrome that included other depression and local symptoms. In the
      pile sorts, we focused on investigating mood disorders and confirmed that four of
      the locally described symptoms formed part of a local depression-like illness.
      The results suggest that depression occurs among this population and support the
      local content validity of depression assessment instruments, such as the
      Depression section of the Hopkins Symptom Checklist. Similar independent evidence
      of validity is missing from most cross-cultural surveys. Our work supports the
      need and feasibility for collecting this supporting evidence prior to conducting
      cross-cultural surveys using existing instruments.

PMID- 11339321
TI  - Prevalence of dissociative disorders among psychiatric inpatients in a German
      university clinic.
AB  - The aim of the study was to determine the frequency of dissociative disorders
      among psychiatric inpatients in Germany and to investigate the relationship
      between childhood trauma and dissociation. The German version of the Dissociative
      Experiences Scale (DES), the Fragebogen fur Dissoziative Symptome (FDS), was used
      to screen 115 consecutive inpatients admitted to the psychiatric clinic of a
      university hospital. Patients with FDS scores higher than 20 were interviewed by
      a trained clinician, using the German translation of the Structured Clinical
      Interview for DSM-IV Dissociative Disorders (SCID-D-R). The German version of the
      Childhood Trauma Questionnaire (CTQ) was administered to investigate prevalence
      of childhood trauma and relations between childhood trauma and dissociation in
      adult life. Twenty-five of the 115 patients (21.7%) had a score higher than 20 on
      the FDS. Of these, 15 patients were interviewed with the SCID-D-R. One patient
      was diagnosed with a dissociative identity disorder, three with dissociative
      disorders not otherwise specified, and one patient with depersonalization
      disorder. All diagnoses were confirmed clinically. A significant positive
      relationship was found between the severity of childhood trauma and dissociation.
      Dissociative disorders are common among German psychiatric inpatients. Clinicians
      who work in psychiatric inpatient units should be mindful of these disorders.

PMID- 11339322
TI  - The relation of social support-seeking to quality of life in schizophrenia.
AB  - Social support-seeking has been shown to improve the outcome of schizophrenia.
      However, no study to date has documented the impact of social support seeking on
      self-perceived quality of life in schizophrenia, particularly not on the relation
      between symptoms and quality of life. The present study explored this issue with
      a sample of 58 outpatients diagnosed with schizophrenia without comorbidity.
      Social support seeking, symptoms (positive, negative, and extrapyramidal), and
      multidimensional self-reported quality of life were assessed cross-sectionally.
      Negative symptoms were inversely related to the quality of life domain of
      activities of daily living. Other symptoms and social support-seeking were not
      related to quality of life, and social support-seeking did not interact with
      symptoms in their relation to quality of life. Social support-seeking may thus
      not be beneficial (nor disruptive) as a way of coping with symptoms in
      schizophrenia. More studies are needed in order to investigate the relation of
      social support-seeking to symptoms and to quality of life in serious mental
      illnesses such as schizophrenia, so that interventions with persons suffering
      from these disorders may be better guided.

PMID- 11339323
TI  - Prevalence of neuropathological indicators among acute psychiatric inpatients.

PMID- 11339324
TI  - Predischarge linkage and aftercare contact among dually-diagnosed public
      psychiatric patients.

PMID- 11339325
TI  - Computational flow modeling of the left ventricle based on in vivo MRI data:
      initial experience.
AB  - A combined computational fluid dynamics (CFD) and magnetic resonance imaging
      (MRI) methodology has been developed to simulate blood flow in heart chambers,
      with specific application in the present study to the human left ventricle. The
      proposed framework employs MRI scans of a human heart to obtain geometric data,
      which are then used for the CFD simulations. These latter are accomplished by
      geometrical modeling of the ventricle using time-resolved anatomical slices of
      the ventricular geometry and imposition of inflow/outflow conditions at orifices
      notionally representing the mitral and aortic valves. The predicted flow
      structure evolution and physiologically relevant flow characteristics were
      examined and compared to existing information. The CFD model convincingly
      captures the three-dimensional contraction and expansion phases of endocardial
      motion in the left ventricle, allowing simulation of dominant flow features, such
      as the vortices and swirling structures. These results were qualitatively
      consistent with previous physiological and clinical experiments on in vivo
      ventricular chambers, but the accuracy of the simulated velocities was limited
      largely by the anatomical shortcomings in the valve region. The study also
      indicated areas in which the methodology requires improvement and extension.

PMID- 11339326
TI  - Numerical simulation of enhanced external counterpulsation.
AB  - Enhanced external counterpulsation (EECP) is a noninvasive, counterpulsative
      method to provide temporary aid to the failing heart by sequentially inflating
      cuffs on the lower extremity out-of-phase with the left ventricle. Optimization
      of the method necessitates consideration of the hemodynamics created by EECP and
      the mode of action providing patient benefit. A computational model based on the
      governing one-dimensional equations is developed that simulates cardiovascular
      hemodynamics during EECP. The model includes a 30-element arterial system
      including the left ventricle, bifurcations, and peripheral arterial vessels.
      Effects of vessel collapse as external pressure is applied, arterial refilling on
      pressure release, changes in aortic pressure, and shear stress generated in the
      arteries are each investigated. Device parameters are systematically varied to
      determine their effect on system performance. Results show the potential for
      significant collapse and shear augmentation throughout the arteries of the lower
      extremity. Performance is strongly influenced by the mean level of external
      pressurization and the timing of cuff inflation, but less so by the relative
      timing and pressure differences between cuff segments.

PMID- 11339327
TI  - Modeling advection and diffusion of oxygen in complex vascular networks.
AB  - A realistic geometric model for the three-dimensional capillary network geometry
      is used as a framework for studying the transport and consumption of oxygen in
      cardiac tissue. The nontree-like capillary network conforms to the available
      morphometric statistics and is supplied by a single arterial source and drains
      into a pair of venular sinks. We explore steady-state oxygen transport and
      consumption in the tissue using a mathematical model which accounts for advection
      in the vascular network, nonlinear binding of dissolved oxygen to hemoglobin and
      myoglobin, passive diffusion of freely dissolved and protein-bound oxygen, and
      Michaelis-Menten consumption in the parenchymal tissue. The advection velocity
      field is found by solving the hemodynamic problem for flow throughout the
      network. The resulting system is described by a set of coupled nonlinear elliptic
      equations, which are solved using a finite-difference numerical approximation. We
      find that coupled advection and diffusion in the three-dimensional system enhance
      the dispersion of oxygen in the tissue compared to the predictions of simplified
      axially distributed models, and that no "lethal corner," or oxygen-deprived
      region occurs for physiologically reasonable values for flow and consumption.
      Concentrations of 0.5-1.0 mM myoglobin facilitate the transport of oxygen and
      thereby protect the tissue from hypoxia at levels near its P50, that is, when
      local oxygen consumption rates are close to those of delivery by flow and
      myoglobin-facilitated diffusion, a fairly narrow range.

PMID- 11339328
TI  - Parameters of postocclusive reactive hyperemia measured by near infrared
      spectroscopy in patients with peripheral vascular disease and in healthy
      volunteers.
AB  - The main purpose of our study was to determine the parameters of the
      postocclusive reactive hyperemia test that could help and provide the clinician
      with information about the tissue oxygenation, the severity of the disease, and
      the results of the applied therapies. Near infrared spectroscopy (NIRS) proved to
      be a valid noninvasive trend monitor useful for investigating the physiology of
      oxygen transport to tissue. Important advantages of NIRS over transcutaneous
      oximetry (TcpO2) are: (a) a more dynamic nature of the NIRS signals which
      reflects more closely the actual response of the peripheral vasculature to the
      occlusive provocation; (b) larger sampling volume; and (c) the ability of
      assessing tissue oxygenation at deeper tissue levels. We demonstrated that the
      time parameters of reactive hyperemia, the rate of reactive hyperemia, and the
      maximal change during reactive hyperemia, all calculated from the oxyhemoglobin
      (HbO2) signal of the NIRS, clearly distinguish between healthy volunteers and
      patients with vascular disorder. The time parameters of reactive hyperemia were
      significantly longer (p<0.01), and the rate of reactive hyperemia (p=0.01) as
      well as the maximal change during reactive hyperemia (p=0.02) were significantly
      lower in patient group compared to healthy volunteers. These parameters were also
      in good correlation with the values of ankle brachial index (ABI) and the resting
      values of oxygen partial pressure (TcpO2). Values of the chosen parameters
      obtained from the HbO2 signal were further compared between groups of diabetic
      and nondiabetic patients with peripheral vascular disease. Although longer time
      parameters of reactive hyperemia and lower rates of hyperemic response were
      detected, the difference between both groups was not statistically significant.

PMID- 11339329
TI  - A mechanistic model of acute platelet accumulation in thrombogenic stenoses.
AB  - Thrombosis on an atherosclerotic lesion can cause heart attack or stroke.
      Thrombosis may be triggered by plaque rupture or erosion, creating a thrombogenic
      stenosis. To measure and model this situation, collagen-coated stenoses have been
      exposed to nonanticoagulated blood in a baboon ex vivo shunt. The maximum rate of
      platelet accumulation, measured using a gamma camera, was highest in the throat
      region of moderate and severe stenoses, and increased with increasing stenosis
      severity. A species transport model of platelet accumulation was developed, which
      included mechanisms of convection, shear-enhanced diffusion, near-wall platelet
      concentration, and a kinetic model of platelet activation and aggregation. The
      model accurately reproduced the average spatial pattern and time rate of platelet
      accumulation in the upstream and throat regions of the stenosis, where shear
      enhanced diffusivity increased platelet transport in the stenosis throat.
      Downstream of the throat where flow is complicated by recirculation, the model
      computed a transport-limited region with lower than measured platelet
      accumulation, suggesting that fluid-phase platelet activation may significantly
      affect both transport and adhesion rates in the poststenotic region. This model
      may provide an initial quantitative estimate of the likelihood of occlusive
      thrombus in individual patients due to plaque erosion, artery spasm, incomplete
      angioplasty, or plaque rupture.

PMID- 11339330
TI  - Identification of static and dynamic components of reflex sensitivity in spastic
      elbow flexors using a muscle activation model.
AB  - Static and dynamic components of the stretch reflex were studied in elbow flexors
      of 13 hemiparetic brain-injured individuals. Constant-velocity joint rotations
      were applied to the elbow, and the resulting stretch reflex torque and
      electromyographic responses were recorded in the biceps brachii and
      brachioradialis muscles. Ten elbow extension velocities between 6 and 150 deg s(
      1) were applied in random order. The resulting reflex torque response was plotted
      as a function of elbow angle and fitted with a mathematical model designed to
      depict elbow flexor activation. We found that four of the six model parameters
      were essentially independent of test velocity. Conversely, 73% (19/26) of cases
      involving the other two model parameters were dependent on velocity of joint
      extension (p<0.05). We conclude from these results that four of the model
      parameters reflect the static reflex response while the two remaining velocity
      dependent parameters reflect the dynamic reflex response. To describe overall
      velocity dependence of stretch reflexes in spastic elbow muscles, the two dynamic
      reflex parameters were fitted to a fractional exponential function of velocity,
      similar to a model previously used to describe spindle firing rate in the cat
      hindlimb. We found that the mean velocity exponent of the dynamic reflex
      parameters was 0.24 + 0.17 (s.d.) (N = 13), a value similar to that for muscle
      spindle velocity sensitivity in reduced animal preparations. We conclude that
      both static and dynamic reflex sensitivities can be measured by examining
      different aspects of the torque/angle relation associated with the reflex
      response to a large-amplitude ramp stretch of the elbow.

PMID- 11339331
TI  - Computational models of antibody-based tumor imaging and treatment protocols.
AB  - We present improved computational models for investigating monoclonal antibody
      based protocols for diagnostic imaging and therapy of solid tumors. Our earlier
      models used a boundary condition (Dirichlet) that specified concentrations of
      diffusing molecular species at the interface between a prevascular tumor nodule
      and surrounding normal tissue. Here we introduce a concentration-dependent flux
      boundary condition with finite rates of diffusion in the normal tissue. We then
      study the effects of this new condition on the tumor's temporal uptake and
      spatial distribution of radiolabeled targeting agents. We compare these results
      to ones obtained with the Dirichlet boundary condition and also conduct parameter
      sensitivity analyses. Introducing finite diffusivity for any molecular species in
      normal tissue retards its delivery to and removal from the tumor nodule. Effects
      are protocol- and dose regimen-dependent: generally, however, mean radionuclide
      concentration and tumor-to-blood ratio declined, whereas relative exposure and
      mean residence time increased. Finite diffusivity exacerbates the negative
      effects of antigen internalization. Also, the sensitivity analyses show that mean
      concentration and tumor-to-blood ratio are quite sensitive to transcapillary
      permeability and lymphatic efflux values, yet relatively insensitive to precise
      values of diffusion coefficients. Our analysis underscores that knowledge of
      antigen internalization rates and doses required to saturate antigen in the tumor
      will be important for exploiting antibody-based imaging and treatment approaches.

PMID- 11339332
TI  - Human visual function in the North Carolina clinical study on possible estuary
      associated syndrome.
AB  - The U.S. Environmental Protection Agency assisted the North Carolina Department
      of Health and Human Services in conducting a study to investigate the potential
      for an association between fish kills in the North Carolina estuary system and
      the risk for persistent health effects. Impetus for the study was recent evidence
      suggesting that estuarine dinoflagellates, including members of the toxic
      Pfiesteria complex (TPC), P. piscicida and P. schumwayae, may release a toxin(s)
      that kills fish and adversely affects human health. This report describes one
      component of the study in which visual system function was assessed. Participants
      working primarily in estuaries inhabited by TPC or in off-shore waters thought
      not to contain TPC were studied. The potentially exposed estuary (n = 22) and
      unexposed offshore (n = 20) workers were matched for age, gender, and education.
      Visual acuity did not differ significantly between the cohorts, but visual
      contrast sensitivity (VCS), an indicator of visual pattern-detection ability for
      stimuli of various sizes, was significantly reduced by about 30% in the estuary
      relative to the offshore cohort. A further analysis that excluded participants
      having a history possibly predictive of neuropsychological impairment showed a
      similar VCS reduction. Additional analyses indicated that differences between the
      cohorts in age, education, smoking, alcohol consumption, and total time spent on
      any water did not account for the difference in VCS. Exploratory analyses
      suggested a possible association between the magnitude of VCS reduction and hours
      spent in contact with a fish kill. The profile of VCS deficit across stimulus
      sizes resembled that seen in organic solvent-exposed workers, but an assessment
      of occupational solvent, and other neurotoxicant, exposures did not indicate
      differences between the cohorts. These results suggest that factor(s) associated
      with the North Carolina estuaries, including the possibility of exposure to TPC
      toxin(s), may impair visual system function.

PMID- 11339333
TI  - An event-by-event probabilistic methodology for assessing the health risks of
      persistent chemicals in fish: a case study at the Palos Verdes Shelf.
AB  - A human health risk assessment of recreational anglers who consume fish from the
      Palos Verdes Shelf was conducted. The uptake of DDT, DDE, and DDD (collectively
      total DDT or tDDT) and polychlorinated biphenyls (PCBs) due to fish ingestion was
      characterized using Monte Carlo techniques. This analysis relied upon 176
      probability density functions developed from over 300,000 individual pieces of
      information to represent 17 different exposure factors that influence the human
      uptake of persistent organic chemicals in fish. The carcinogenic and
      noncarcinogenic risks were estimated using a microexposure event modeling
      approach that estimates exposure on an event-by-event basis. This evaluation
      relied upon several large studies that provided site-specific data on angler
      behavior and concentratioins of chemicals in 13 fish species. Our results
      indicate that the median theoretical increased lifetime cancer risk associated
      with estimated exposure to tDDT and PCBs was 5 x 10(-8) for anglers who fish on
      commercial passenger fishing vessels (CPFVs) and who catch and eat fish from the
      Palos Verdes Shelf. The mean risk for these anglers was 2 x 10(-7), and the 95th
      percentile risk was 8 x 10(-7). At the 9.5th percentile, the hazard quotients for
      anglers were less than 1, indicating that noncancer effects are unlikely. These
      results are in contrast with prior risk assessments of this site that suggested
      that consumption of white croaker alone posed a cancer risk of 2 x 10(-3) and a
      hazard quotient of 32. Our results were validated by their agreement with several
      independent local studies regarding fishing and consumption practices. This
      assessment indicates that the levels of tDDT and PCB in fish at the Palos Verdes
      Shelf do not pose a significant risk to human health among recreational anglers.
      Based on the size of the local angler population, no cases of cancer would be
      expected to result from eating Palos Verdes Shelf fish. The methodology used here
      should be applicable to characterizing the risks to those who ingest fish from
      the waterways of most industrialized nations.

PMID- 11339334
TI  - Vasorelaxation induced by L-glutamate in porcine coronary arteries.
AB  - Isolated porcine coronary arteries (PCA) contracted by depolarization with high
      K0 or by histamine (10 microM) were relaxed concentration-dependently by glutamic
      acid, aspartic acid, N-methyl-D-aspartate (NMDA) and, gamma-aminobutyric acid
      (GABA). In the PCA preparations contracted by high K0 or histamine the effects
      were monophasic, but the histamine-induced effects were more sustained and of
      larger amplitude. The ED50 values of cumulative concentration-response (CCR)
      curves obtained for the relaxation induced by L-glutamate in histamine-stimulated
      PCA preparations were shifted from 0.8 mM to 0.25 microM in presence of 1 mM
      glycine, a co-agonist required for the activation of NMDA receptors. The
      relaxations resulting from low-affinity binding of L-glutamic were dependent on
      Ca0 as evidenced by the shift of CCR curves to the right in the presence of 5-100
      mM K0. In contrast, CCR curves obtained for contractions induced by NaF (1.5-12
      mM), were significantly shifted to the left (from 6.3 to 3.1 mM). A depression of
      the maximum effect observed at higher F- concentrations was reversed by addition
      of 5 mM Mg0. Data show that glutamate induces a vasorelaxation that may be
      associated with symptoms seen in Chinese restaurant syndrome.

PMID- 11339335
TI  - A control theoretic approach to containing the spread of rabies.
AB  - Many problems in medicine and biology involve some kind of spatial spread, and
      quite often the need to control it. A large proportion of medical and biological
      systems distinguish themselves from those found in engineering by the way the
      control acts. We illustrate this by considering the specific example of the
      spread of rabies among foxes. We first give a brief description of a model
      proposed by Murray et al. (Murray, J. D., Stanley, E. A. & Brown, D. L., Proc. R.
      Soc. Lond., B 229, 111-150 (1986)), which we extend to include the control
      mechanism. The problem is to prevent the spread of rabies by vaccinating foxes
      via the distribution of bait in a region around an observed outbreak. The
      extended model can be formulated as a nonlinear time-varying control system
      described by partial differential equations. In contrast to most engineering type
      control problems, the control does not continuously affect the system but only
      acts through the initial distributions. We briefly outline a general theory
      developed for dealing with such nonlinear systems by the use of a fixed point
      theorem. The problem and the theory are illustrated by some numerical
      simulations.

PMID- 11339336
TI  - Optimal chemotherapy regimens: influence of tumours on normal cells and several
      toxicity constraints.
AB  - Cancer chemotherapy for the case of one drug is studied. The negative and
      inhibiting effect of the tumour on normal cells is taken into account. Under
      certain assumptions, we determine the optimal regimen that minimizes the tumour
      burden at the end of a fixed period of therapy while maintaining certain normal
      cell populations above prescribed levels. More precisely, it is demonstrated that
      the optimal strategy corresponds to injection of the drug at the maximal rate.

PMID- 11339337
TI  - On the zeros of a third degree exponential polynomial with applications to a
      delayed model for the control of testosterone secretion.
AB  - In this paper, we first study the distribution of the zeros of a third degree
      exponential polynomial. Then we apply the obtained results to a delay model for
      the control of testosterone secretion. It is shown that under certain assumptions
      on the coefficients the steady state of the delay model is asymptotically stable
      for all delay values. Under another set of conditions, there is a critical delay
      value, the steady state is stable when the delay is less than the critical value
      and unstable when the delay is greater than the critical value. Thus,
      oscillations via Hopf bifurcation occur at the steady state when the delay passes
      through the critical value. Numerical simulations are presented to illustrate the
      results.

PMID- 11339338
TI  - Control analysis of the Rose-Hindmarsh model for neural activity.
AB  - It is well known that vasopressin cells fire action potentials in bursts, but
      also have the ability to continuously discharge or have long periods of silence.
      Experimentally, various external stimuli can be applied to the vasopressin cell
      in order to manipulate the patterns of discharge observed. In this paper, the
      Rose-Hindmarsh model is used to describe the discharging of a single vasopressin
      cell. The range of parameter values which makes the model display the various
      patterns observed in vivo are described. It is shown that the model can be
      controlled to follow desired patterns of discharge and thus mimic external
      stimulation.

PMID- 11339339
TI  - Physiological flow waveform in a rigid elliptical vessel.
AB  - A procedure to model the velocity and wall shear stress for a physiological flow
      in a non-cylindrical vessel is presented. The work describes how a vessel with an
      elliptical cross section may be used to represent flow in compressed or partially
      occluded arteries and veins. The procedure was applied to produce a simulation of
      a physiological flow in a straight rigid vessel with a slightly elliptical cross
      section (ellipticity, epsilon = 0.8). Fourier analysis was performed on a
      physiological flow waveform. Flow in the common carotid artery was satisfactorily
      represented (Pearson correlation coefficient, r > 95%) with a series of five
      harmonic terms. Expressions involving a linear combination of ordinary and
      modified Mathieu functions were used to describe the velocity and wall shear
      stress for each harmonic. An outline of the procedure, and the expressions, which
      were used to compute the characteristic Mathieu numbers and coefficients is
      illustrated with their behaviour at the fundamental and Nyquist frequencies.
      Superposition of the individual contributions to the velocity and wall shear
      stress allowed the calculation of the overall properties of the flow.

PMID- 11339340
TI  - Health for all in the new millennium.

PMID- 11339341
TI  - The UN in crisis?
AB  - The United Nations (UN), the principal role of which is dealing with crises, has
      been in almost perpetual crisis since its foundation. The situation has become
      worse in the 1990s, a time when the need for an effective UN has been greater
      than ever, to cope with issues such as climate-change, pollution and the
      consequences of globalization. The current crisis has various aspects.
      Politically there have been widely publicized failures in peacekeeping, largely
      due to the Security Council being a body of compromise, while successes in
      peacekeeping have been largely ignored. In the economic and social field,
      influence has passed to the International Monetary Fund (IMF) and the World Bank.
      Development aid has plummeted, despite its key role in peace and security, and so
      an integrated approach to development and security is urgently needed. The UN has
      been constantly under-funded, with the failure of the United States (US) to pay
      its dues a key factor. Reform of the UN is vital, but the vested interests of
      member states make root-and-branch reform virtually impossible. Public pressure
      for reform can come from non-governmental organizations, perhaps coordinated
      through the Internet.

PMID- 11339343
TI  - The incidence of childhood leukaemia in West Berkshire.
AB  - This paper gives an overview of local work on the incidence of childhood
      leukaemia in West Berkshire since 1971. The most recently published figures show
      that between 1972-96, a total of 106 children contracted leukaemia when 81 cases
      would have been expected in the under 14s. Within ten kilometres of the nuclear
      establishments at Aldermaston and Burghfield, the risk of a child getting
      leukaemia, which is very small (400 children a year in the UK) is none the less
      doubled in under-fives meaning that one more child a year is affected. There is
      also an increased incidence of all cancers in this age group and geographical
      area. Theories as to why this should be abound, but until the cause of cancer is
      fully understood, and what the part of radiation in the process could be, no firm
      measures can be taken to redress the balance.

PMID- 11339342
TI  - Stories of pre-war, war and exile: Bosnian refugee children in Sweden.
AB  - While standardized questionnaires produce counts of isolated events, a semi
      structured interview derives a story, a complex narrative in time and place.
      Ninety Bosnian refugee children and adolescents (ages 1-20), resettled in Sweden,
      were assessed in a semi-structured clinical interview designed to identify and
      offer support to children at risk. A family-child account of traumatic exposure
      was analysed quantitatively and qualitatively. Type-stories or clusters of
      experience were identified for three distinct periods: prior to war, during war,
      and after war in exile. The extent of trauma-stress exposure during each of these
      periods proved unrelated. Pre-war experience presented as preponderantly good and
      safe. Differences in child exposure during war and exile could be understood in
      relation to identifiable socio-demographic factors; particularly ethnic
      background, social class, child age and family size. Further, the stories derived
      cast light on the equity of Swedish refugee reception, exposing both egalitarian
      and discriminatory tendencies.

PMID- 11339344
TI  - Sustainable energy, economic growth and public health.
AB  - Dramatic economic growth over the last 50 years has been accompanied by widening
      inequalities world-wide in wealth and energy consumption, diminished life
      expectancy in some countries, and deteriorating indices of environmental
      sustainability including loss of bio-diversity. Raised output of carbon dioxide
      (CO2) and other greenhouse gases due to increased economic and industrial
      activity is causing progressive climate change, leading in turn to direct and
      indirect adverse effects on health. Emissions of greenhouse gases can be lowered
      by increased use of renewable energy sources, for example, wind power in the
      United Kingdom (UK), greater energy efficiency and other measures to promote
      sustainability. The experience of some developing countries shows that favourable
      indicators of health and development can accompany a low output of greenhouse
      gases. It is unclear whether contemporary political and social systems can
      deliver improved human development without increased use of fossil fuels and
      other resources.

PMID- 11339345
TI  - Civilians and war: a review and historical overview of the involvement of non
      combatant populations in conflict situations.
AB  - The effects of light weapons are now regularly seen on television and are
      becoming an international issue, particularly regarding their impact on
      civilians. It is claimed that 80% or more of deaths and injuries in today's wars
      are civilian; there is no objective evidence for this as little accurate
      information is available. Recent surveys suggest, however, a proportion of
      between 35 and 65%--still far too high considering the protection to which
      civilians are entitled under international humanitarian law. It is proposed the
      problem arises from twentieth-century killing power in the hands of individuals
      with fifteenth-century discipline and organization. Recent systematic surveys
      distinguish between civilian deaths from light weapons in combat and non-combat
      situations. A high proportion of combat deaths is due to fragmenting weapons such
      as mortars targeted on populated areas. Many weapon-related deaths in non-combat
      situations are accidental (cleaning weapons, handling by children during play)
      and others are related to domestic disputes. The availability and use of weapons
      also affects civilians indirectly in many ways, such as ill-health in refugees,
      psychosocial effects on women and children, and economic and environmental
      consequences. A variety of schemes exist to reduce the availability of light
      weapons and reintegrate their users into society. The international community
      must extend and make better use of these measures.

PMID- 11339346
TI  - Globalization and health.
AB  - Globalization means different things to different people; a general definition is
      the increasing movement of information, material and people across borders. It
      can be considered in terms of five conflicting but inter-relating themes,
      economic transformation; new patterns of trade; an increasing poverty gap
      associated with widening health inequalities; the revolution in electronic
      communication; and the growing role of non-state actors, such as non-governmental
      organizations and transnational corporations, in global governance. Globalization
      is both an opportunity and a threat, but it is not inexorable. Successful action
      against its undesirable aspects is possible.

PMID- 11339348
TI  - Cultures of killing: war and peace.

PMID- 11339347
TI  - Child soldiers--and others.

PMID- 11339349
TI  - Immune responses to DNA in normal and aberrant immunity.
AB  - Because of structural microheterogeneity, DNA can exert powerful effects that
      lead to immune system activation as well as antibody induction. These activating
      effects resemble those ofendotoxin and result from sequences that occur much more
      commonly in bacterial DNA than in mammalian DNA. In contrast, mammalian DNA can
      inhibit the response to bacterial DNA as well as other stimuli and may serve a
      counterregulatory role during infection. The recognition of the immune effects of
      DNA is relevant to the pathogenesis of a variety of infectious and inflammatory
      diseases including systemic lupus erythematosus, a prototypic autoimmune disease
      characterized by anti-DNA autoantibodies.

PMID- 11339351
TI  - Immunoglobulin in the control of complement action.
AB  - Complement is a critical element of innate immunity, protecting individuals from
      a wide variety of microbial infections. This group of proteins is responsible for
      many features of inflammation and tissue damage. Because of its ability to
      mediate autoimmune tissue damage and to destroy host tissues, it is under tight
      regulation with many circulating and cell-membrane-bound complement regulatory
      proteins. The function of much of the circulating immunoglobulin has never been
      defined. We have advanced the hypothesis that one function of circulating
      immunoglobulin is to down-regulate complement attack on host tissues in the
      presence of anti-self antibody. The data to support this hypothesis are reviewed.
      The data are consistent with the suggestion that one mechanism of action of
      intravenous immunoglobulin, used to treat patients with a variety of autoimmune
      diseases, is prevention of complement-mediated attack on host tissues.

PMID- 11339350
TI  - Accessibility control of T cell receptor gene rearrangement in developing
      thymocytes. The TCR alpha/delta locus.
AB  - The joining of T cell receptor (TCR) and immunoglobulin (Ig) gene segments
      through the process of V(D)J recombination occurs in a lineage-specific and
      developmental-stage-specific way during the early stages of lymphocyte
      development. Such developmental regulation is thought to be mediated through the
      control of gene segment accessibility to the recombinase. We have studied the
      regulation of V(D)J recombination at the TCR alpha/delta locus, because this
      locus provides a fascinating model in which distinct sets of gene segments are
      activated at different stages of T cell development. The transcriptional
      enhancers Edelta and Ealpha have been implicated as critical regulators that, in
      conjunction with other cis-acting elements, confer region-specific and
      developmental-stage-specific changes in gene segment accessibility within TCR
      alpha/delta locus chromatin. Current work suggests that they may do so by
      functioning as regional modulators of histone acetylation.

PMID- 11339353
TI  - Natural killer cell-endothelial cell interactions in xenotransplantation.
AB  - Interest in xenotransplantation derives from the documented need for more organs
      and tissues than can be expected from living or cadaveric donors. Although the
      barriers to xenotransplantation are formidable, the scientific rewards in
      addressing these problems have been significant. The first and most potent
      barrier to xenotransplantation is hyperacute rejection mediated by xenoreactive
      natural antibodies and serum complement. The majority of the xenoreactive
      antibodies appear to be directed at terminal galactose epitopes, especially gal
      alpha1-3 gal. Significant progress has been made in surmounting hyperacute
      rejection, and this has led to an examination of underlying mechanisms of delayed
      xenograft rejection. One of these delayed mechanisms concerns the potential role
      of graft recipient, natural killer (NK) cells. NK cells can cause variable, low
      level cytotoxicity of xenogeneic endothelial cells in vitro that may be enhanced
      in the presence of xenoreactive IgG. The specificity of NK cell-mediated
      cytotoxicity appears to overlap with a major subset of xenoreactive natural
      antibodies. These cytotoxic interactions can be regulated by "humanizing" the
      endothelial cells through expression of the appropriate human MHC class I genes.
      More important, NK cells induce endothelial cell activation, which results in
      changing the nature of the endothelial cell surface from an anticoagulant surface
      to a procoagulant surface. These findings parallel those observed in allogeneic
      NK cell-endothelial cell interactions and suggest these important observations
      may be extended to NK cell-endothelial cell interactions in general.

PMID- 11339352
TI  - Tolerance induction for solid organ grafts with donor-derived hematopoietic
      reconstitution.
AB  - Tolerance of transplanted tissue has been a focus of immunologists for decades.
      Indeed, to some the birth of immunology and the search for tolerance of the non
      self are synonymous. One of the most powerful and reproducible methods of
      tolerance induction to allogeneic tissue has involved infusion of donor-specific
      hematopoietic cells. Under certain conditions, such infusion can result in
      hematopoietic reconstitution that can be experimentally accomplished at a variety
      of different time-points in the life of an organism from the in utero period
      through adulthood, reconstitution at each time-point involving consideration of a
      different set of immunological and physiological parameters. When high levels of
      donor-derived hematopoietic reconstitution are achieved, tolerance induction to
      donor-specific antigens is reproducible and long-lasting. Unfortunately, however,
      clinical efforts to achieve such high levels of hematopoietic reconstitution have
      historically been unsuccessful or fraught with complications. Transplantation
      efforts have been plagued by failure of engraftment, graft-vs-host disease
      (GVHD), or severe immunoincompetence of the recipient. Laboratory and clinical
      efforts during the last decade have resulted in a variety of developments that
      may overcome these barriers: (1) methods have been devised in which cells that
      cause GVHD can be depleted from the hematopoietic graft while hematopoietic
      reconstitution potential is preserved, (2) methods of harvesting large numbers of
      cells with multilineage reconstitution potential have been devised (an
      accomplishment that seems to allow the immunological barrier to be overwhelmed),
      and (3) capitalizing on the above two principles, minimally toxic preconditioning
      regimens have been designed that allow allogeneic engraftment. This review will
      focus on some of the experimental and clinical data of the past and the
      experimental and clinical issues that loom ahead.

PMID- 11339354
TI  - T cell immunity in neonates.
AB  - Typically, neonates exhibit decreased or aberrant cellular immune responses when
      compared to adults, resulting in increased susceptibility to infection. However,
      it is clear that newborns are able to generate adult-like protective T cell
      responses under certain conditions. The focus of our research is to understand
      the deficiencies within the neonatal immune system that lead to improper cellular
      responses and how priming conditions can be altered to elicit the appropriate T
      cell response necessary to protect against development of pathogen-induced
      disease. With these goals in mind, we are exploring the attributes of neonatal T
      cells and their development, as well as the conditions during priming that
      influence the resulting response to immune challenge during the neonatal period.

PMID- 11339355
TI  - Links between the immune and coagulation systems: how do "antiphospholipid
      antibodies" cause thrombosis?
AB  - Inflammation and immune activation have been associated with thrombosis in a
      number of settings. We have been interested in the question of how the presence
      of a type of autoantibody, so-called "antiphospholipid" antibody, leads to
      thrombosis. Several mechanisms have been proposed including modulation of tissue
      factor expression, enhancement of procoagulant binding to platelets, and
      interference with antithrombotic mechanisms. We developed a cell-based model of
      coagulation that, unlike current coagulation assays, reflects some of the in vivo
      activities of "antiphospholipid" antibodies. "Antiphospholipid" antibodies
      against the phospholipid-binding protein beta-2-glycoprotein-1 enhance thrombin
      generation in this model system, primarily by enhancing procoagulant reactions on
      tissue factor-bearing cells.

PMID- 11339357
TI  - A genetic investigation of E2A function in lymphocyte development.
AB  - Lymphocytes are derived from hematopoietic stem cells (HSC) following a series of
      regulated differentiation events. Multipotent HSCs become committed to the B cell
      lineage in bone marrow and the T cell lineage in the thymus after receiving
      appropriate signals from the corresponding microenvironment. These committed
      lymphoid cells must then undergo V(D)J recombination at the immunoglobulin gene
      or T cell receptor gene locus resulting in clonal production of functional B or T
      lymphocytes, respectively. Lymphocyte commitment and differentiation are
      accompanied by programmed gene expression or repression events which are driven
      by lineage and stage specific transcription factors. The basic-helix-loop-helix
      (bHLH) transcription factors encoded by the E2A gene are involved in several
      differentiation events during B and T cell development, including lineage
      commitment, initiation of V(D)J recombination, and antigen receptor mediated
      proliferation and differentiation. Several recent reviews have provided a
      comprehensive discussion of biochemical, cellular, and genetic research on E2A
      function in lymphocyte development (1,2). Here, we only discuss some of the
      genetic approaches our laboratory (except where it is noted) has undertaken to
      investigate the molecular pathways mediated by E2A transcription factors in
      lymphocyte development.

PMID- 11339356
TI  - Studies of the humoral immune response.
AB  - The humoral immune response arises from a complex choreography of cells and
      molecules that interact to produce lasting and effective defenses against
      pathogens. For more than fifteen years, our laboratory has studied how humoral
      responses are initiated, how they mature, and how they are remembered. This work
      has come from many hands and in this brief synopsis, I cannot provide the full
      recognition that my students, postdoctoral fellows, and collaborators merit. I
      hope that my colleagues can accept this translucence and know that their efforts
      are recognized and deeply appreciated, nonetheless.

PMID- 11339358
TI  - Antigen-specific  immunity. Th cell-dependent B cell responses.
AB  - Helper T cell-regulated B cell responses constitute a major component of the
      primary immune response to many pathogens. The subsequent development of antigen
      specific immune memory is one critical outcome of this primary adaptive immune
      response. Antigen-specific immunity develops through a series of intercellular
      information exchanges organized around cognate T cell receptor-peptide/MHC
      interactions. Here, we discuss these complex molecularevents
      andtheircellularconsequences in a serial synapsis model of adaptive immunity. Our
      laboratory has developed strategies to isolate antigen-specific Th cells and B
      cells to analyze gene expression and cellular function in single responding
      lymphocytes directly ex vivo. These studies provide insight into the regulation
      and cellular organization of antigen-specific immune responses in vivo.

PMID- 11339359
TI  - Advances in the understanding and treatment of human severe combined
      immunodeficiency.
AB  - Human severe combined immunodeficiency (SCID) can result from mutations in any
      one of at least seven different genes, including those for adenosine deaminase,
      the common cytokine receptor gamma chain, Janus kinase 3, IL-7 receptor alpha
      chain, recombinase activation genes 1 and 2, and CD45. Except for adenosine
      deaminase, knowledge concerning the latter causes of human SCID has accrued since
      1993. Advances in the treatment of this syndrome have been no less significant.
      Since 1982 it has been possible, by rigorous depletion of T cells from the donor
      marrow, to use related marrow donors other than HLA-identical siblings for
      successful treatment of infants with this condition. The success rate with the
      latter type of transplant exceeds 95% if a transplant can be performed within the
      first 3.5 mo of life, making early diagnosis crucial. Recently, gene therapy has
      also been successful in infants with X-linked SCID.

PMID- 11339360
TI  - The human thymus during aging.
AB  - The human thymus is required for establishment of a normal T cell repertoire in
      fetal development, as children born without a thymus (DiGeorge Syndrome) lack
      thymus-derived (T) and T cell immunity. While the function of the thymus in
      children for production of new T cells is clear, it has not been obvious that the
      adult thymus can produce significant numbers of new T cells. Until recently, no
      assays were available to directly evaluate postnatal thymic function. This paper
      reviews work on human thymic aging at Duke University School of Medicine and
      discusses the relevance of this work to devising new strategies for T cell immune
      reconstitution in man.

PMID- 11339361
TI  - HIV vaccine development at Duke University Medical Center.
AB  - With the AIDS epidemic continuing to spread throughout the world, development of
      a safe, practical, and effective HIV vaccine is a national priority. HIV vaccine
      research efforts are currently targeted towards design of HIV immunogens that
      induce both cellular and humoral immunity. This brief review summarizes ongoing
      work at the Duke University School of Medicine on HIV vaccine development.

PMID- 11339362
TI  - Function and regulation of chemoattractant receptors.
AB  - Phagocyte migration and activation at sites of inflammation is mediated through
      chemoattractant receptors that are coupled to G-proteins. Early studies from our
      laboratory demonstrated G-protein-mediated phospholipase C activation by
      chemoattractants. Recently, this laboratory developed cellular and animal models
      to allow biochemical, cell biological and molecular genetic approaches to be used
      in determining the mechanisms of chemoattractant receptor function, regulation,
      and cross regulation. These studies provided evidence that chemoattractant
      receptors activate distinct pathways for chemotaxis and exocytosis and cross
      regulate each other's function at multiple levels. A major site of regulation is
      through phosphorylation of receptors by G-protein-coupled receptor kinases and by
      protein kinase C. In addition, the activation of phospholipase C by
      chemoattractants is also regulated at additional sites distal to receptor
      phosphorylation. These may include modulation of G-protein activation by
      regulators of G-protein signaling (RGS) and modification of phospholipase C.
      Phosphorylation of phospholipase Cbeta3 by both protein kinase A and protein
      kinase C has been demonstrated. The function and regulation of chemoattractant
      receptors are also being examined in mouse models. In these studies, mice
      deficient in leukotriene B4 receptors have been generated by targeted gene
      disruption. These mice displayed reduced neutrophil accumulation in certain
      inflammation models and sex-related differences in platelet-activating-factor
      induced anaphylaxis.

PMID- 11339363
TI  - CD19 regulates intrinsic B lymphocyte signal transduction and activation through
      a novel mechanism of processive amplification.
AB  - The fate of B lymphocytes is dependent on intrinsic and B cell antigen receptor
      (BCR)-induced signals. These signals are interpreted and modified by response
      regulators such as CD19 that govern mature B cell activation. The current
      understanding of how CD19 governs B lymphocyte signaling is outlined in this
      review. Primarily, CD19 establishes a novel Src-family kinase amplification loop
      that regulates basal signal transduction thresholds in resting B cells. Moreover,
      CD19 amplifies Src-family kinase activation following BCR ligation. CD19
      amplification of Lyn activity leads to processive phosphorylation of CD19 and
      downstream substrates including CD22. Phosphorylated CD19 recruits other effector
      molecules including Vav, Grb2, phosphoinositide 3-kinase, phospholipase Cgamma2,
      and c-Abl, which may contribute to CD19 regulation of B cell function. CD19/Lyn
      complex formation also regulates phosphorylation of CD22 and FcgammaRIIB, which
      inhibit B cell signal transduction through the recruitment of the SHPI and SHIP
      phosphatases. These observations provide insight into how CD19 governs the
      molecular ordering and intensity of signals transduced in B cells, and how
      perturbations in CD19 expression or signaling function may contribute to
      autoimmunity.

PMID- 11339364
TI  - Adhesion molecule cascades direct lymphocyte recirculation and leukocyte
      migration during inflammation.
AB  - Leukocyte interactions with vascular endothelium are highly orchestrated
      processes that include the capture of free-flowing leukocytes from the blood with
      subsequent leukocyte rolling, arrest, firm adhesion, and ensuing diapedesis.
      These interactions occur under high shear stresses within venules and depend on
      multiple families of adhesion molecules. Many of the adhesion molecules involved
      are now identified. In addition, precise mechanisms underlying their regulation
      and our understanding of how different families of adhesion molecules work
      together is becoming clearer. Specifically, leukocyte/endothelial cell
      interactions such as capture, rolling, and firm adhesion can no longer be viewed
      as occurring in discrete steps mediated by individual families of adhesion
      molecules, but rather as a series of overlapping synergistic interactions among
      adhesion molecules resulting in an adhesion cascade. Although long thought to be
      mediated by distinct adhesion pathways, overlapping adhesion cascades mediate
      normal lymphocyte recirculation to peripheral lymphoid tissues and inflammation
      induced leukocyte migration. These cascades thereby direct leukocyte migration,
      which is essential for the generation of effective inflammatory responses and the
      development of rapid immune responses.

PMID- 11339366
TI  - Immunology at Duke.

PMID- 11339367
TI  - The role of orphan nuclear receptor in thymocyte differentiation and lymphoid
      organ development.
AB  - T lymphocytes differentiate in the thymus through several phenotypically distinct
      stages that are tightly regulated by multiple nuclear transcription factors.
      Immature CD4+CD8+ double positive (DP) thymocytes make up a majority of the
      population in the thymus, and exhibit several phenotypic features distinct from
      mature T cells. DP thymocytes express only about 10% of surface TCR that are
      found on mature T cells and do not proliferate and produce IL-2 in response to
      stimulation. Several critical events of T lymphocyte maturation such as TCRalpha
      gene recombination, positive and negative selection, and CD4/CD8 lineage
      commitment occur around the DP stage. Recent studies from our group and others on
      the orphan nuclear receptor RORgamma and its thymus-specific isoform RORgammat
      support a critical role for this nuclear receptor in the regulation of DP
      thymocyte function. In addition, RORgamma is required for the development of
      lymph nodes and Peyer's patches.

PMID- 11339365
TI  - Nitric oxide synthase 2 and cyclooxygenase 2 interactions in inflammation.
AB  - Nitric oxide (NO) and prostaglandin (PG) E2 produced by NO synthase type 2 (NOS2)
      and cyclooxygenase type 2 (COX2), respectively, are important mediators in
      inflammation. There is much information regarding their roles in models of
      inflammation in mice and in humans with diseases such as rheumatoid arthritis
      (RA). A variety of stimuli including cytokines, microbial components, immune
      complexes, and mechanical stress can induce both NOS2 and COX2 mRNA transcription
      and protein synthesis and enhance inflammation. This has been demonstrated in
      both mice and humans. NOS2-specific inhibitors reduce inflammation in mice, and
      COX2-specific inhibitors reduce inflammation in mice and in humans. There is
      significant cross-talk between PGE2/NO and COX2/NOS2. Treatments that inhibit
      both NOS2 and COX2 should provide the most potent antiinflammatory effects.

PMID- 11339368
TI  - The role of apoptosis in regulating hematopoiesis and hematopoietic stem cells.
AB  - Apoptosis, or the ability of cells to die in an orderly and highly regulated
      manner, is essential for normal development and homeostasis of multicellular
      organisms. Diseases in which deregulation of this process is implicated include
      autoimmune diseases, cancer and Alzheimer's disease. The importance of apoptosis
      for the development and function of lymphoid cells has been extensively
      investigated. Less clear is the role apoptosis plays in regulating early
      progenitor and stem cell compartments. This question is being investigated using
      a transgenic mouse model, H2K-BCL-2, in which all hematopoietic cells have an
      increased resistance to apoptosis. The same transgenic model is also being used
      to address the question whether protection against apoptosis can increase system
      wide resistance to lethal challenges such as irradiation and chemotherapeutic
      agents.

PMID- 11339370
TI  - Prenatal diagnosis of the 22q11.2 deletion syndrome.
AB  - The development of fluorescence in situ hybridization (FISH)- and polymerase
      chain reaction (PCR)-based assays for the detection of deletions of chromosome
      22q11.2 has enabled the medical community to offer couples at risk prenatal
      diagnostic testing. Current indications for testing include a previous child with
      a 22q11.2 deletion or DiGeorge/velocardiofacial syndrome, an affected parent with
      a 22q11.2 deletion, and in utero detection of a conotruncal cardiac defect.
      Antenatal knowledge of the deletion status provides couples and clinicians with
      an accurate diagnosis, prognostic information, and recurrence risk, which may
      assist couples with their reproductive decisions. However, there are limitations
      to prenatal testing, which should be reviewed prior to testing.

PMID- 11339369
TI  - Mutant T cell lines as model systems for the dissection of T cell antigen
      receptor signaling pathways.
AB  - T cell antigen receptor (TCR) ligation triggers a cascade of intracellular
      signaling events that culminate in T cell activation, cytokine gene expression,
      differentiation, or apoptosis. Many of the enzymes and adapter proteins
      responsible for signal propagation from the cell surface TCR to the cytoplasm and
      nucleus have now been identified and molecularly cloned. However, a comprehensive
      understanding of the regulation and functions of these signaling proteins in T
      cells remains a major challenge. Our laboratory has approached this problem
      through the generation of a panel of Jurkat T cell-derived somatic mutants that
      fail to express several critical elements in the TCR-linked signaling cascade.
      This review highlights the use of mutant T cell lines for functional
      characterizations of two of these signaling proteins--the ZAP-70 tyrosine kinase
      and phospholipase C-gamma1.

PMID- 11339371
TI  - Endocrine aspects of the 22q11.2 deletion syndrome.
AB  - Hormonal disorders are common in patients with a 22q11.2 deletion. While
      hypoparathyroidism was the first endocrine disturbance documented in the DiGeorge
      syndrome, growth hormone deficiency, hypothyroidism, and hyperthyroidism are now
      known to occur in patients with a 22q11.2 deletion. This review briefly
      summarizes our current understanding of the spectrum of endocrinological
      manifestations of the 22q11.2 deletion and proposes guidelines for appropriate
      screening and management of endocrine disorders in patients with a 22q11.2
      deletion.

PMID- 11339372
TI  - The 22q11.2 deletion: from diversity to a single gene theory.
AB  - The 22q11 deletion syndromes are a group of conditions in which a characteristic
      spectrum of congenital cardiac defects may be associated with a wide range of
      noncardiological congenital anomalies. These syndromes are all linked by a
      deletion in the long arm of chromosome 22. Although it is a large deletion,
      containing many genes, recent advances have led to the belief that the etiology
      of the diverse abnormalities of these syndromes may be a single gene deletion.
      This review outlines the historical development of the various "22q deletion
      syndromes," including the DiGeorge, velocardiofacial, Takao, Cayler, and CATCH-22
      syndromes, briefly describes the relevant cardiac embryogenesis, and then
      explains how a single gene deletion may encompass the full phenotypic spectrum.

PMID- 11339373
TI  - Phenotype of the 22q11.2 deletion in individuals identified through an affected
      relative: cast a wide FISHing net!
AB  - PURPOSE: The chromosome 22q11.2 deletion has been identified in the majority of
      patients with DiGeorge syndrome, velocardiofacial syndrome, and conotruncal
      anomaly face syndrome and in some patients with the autosomal dominant Opitz
      G/BBB syndrome and Cayler cardiofacial syndrome. In addition, 22q11.2 deletion
      studies are becoming part of a standardized diagnostic workup for some isolated
      defects such as conotruncal cardiac anomalies and velopharyngeal incompetence.
      However, there is little information available on the clinical findings of
      unselected patients. For example, those individuals identified during prenatal
      diagnosis, as part of a generalized screening protocol, or following the
      diagnosis in a relative. This information will be invaluable in defining the
      variability of the disorder and in observing long-term outcome in the absence of
      targeted remediations. This study allows one to examine the first unselected
      cohort of patients and serves to highlight the importance of deletion testing in
      parents of affected probands. METHODS: Thirty individuals with a 22q11.2 deletion
      were identified following the diagnosis in a relative. Nineteen were adults
      ascertained only following the diagnosis in their child, 10 were children
      identified following the diagnosis in their sibling, and one was a child
      diagnosed prenatally following the diagnosis in her parent. RESULTS: Sixty
      percent of patients had no visceral anomalies. In fact, only 6 of the 19 adults
      (32%) and 6 of the 11 children (55%) had major findings which would have brought
      them to medical attention. Deletion sizing demonstrated the same large 3-4 MB
      deletion in most families despite wide inter and intrafamilial variability and
      there was no difference in clinical findings based on the parent of origin. Thus,
      no genotype-phenotype correlations could be made. CONCLUSION: We report the first
      unselected cohort of patients with the 22q11.2 deletion identified through an
      affected relative. Analysis of this series of 30 patients, many with very mild
      manifestations of the deletion, allows one to examine the outcome in individuals
      who lacked specific remediations for this disorder. It emphasizes the importance
      of broadening the index of suspicion in order to provide appropriate recurrence
      risk counseling, cognitive remediation, and medical management. Further, it
      underscores the lack of familial concordance and the current lack of genotype
      phenotype correlations in this disorder, and it raises the possibility that the
      deletion is more common than previously reported.

PMID- 11339374
TI  - Auxological evaluation in patients with DiGeorge/velocardiofacial syndrome
      (deletion 22q11.2 syndrome).
AB  - PURPOSE: Patients with microdeletion of chromosome 22q11.2 (del22q11) were
      studied, in order to evaluate auxological parameters and to correlate growth
      patterns with the presence of main clinical characteristics of the syndrome.
      METHODS: Between January 1995 and March 2000, auxological parameters (weight,
      height, head circumference, and bone age) of 73 patients with del22q11 were
      collected. Five subgroups of patients were distinguished: Group I (37 patients)
      included patients aged between 0.3 and 4 years, Group II (20 patients) included
      patients aged between 5 and 10 years, Group III (16 patients) included patients
      aged between 11 and 16.3 years. The presence or absence of some clinical features
      was correlated to growth patterns. RESULTS: Weight: in Group I, 5 of 37 (13.5%)
      patients were below the 3rd percentile, 29 of 37 (78.3%) were below the mean
      percentile, none was overweight; in Group II, 13 of 20 (65%) patients were
      between the 10th and the 50th percentiles; in Group III, weight corresponded to
      the 97th percentile in 5 of 16 (31.2%) patients, and in 2/16 (12.5%) adolescents,
      the weight measurements were even above the 97th percentile. Height: short
      stature was detected in 7 of 73 (9.6%) of the total patients; the patients with
      short stature were all < 10 years old; the height was within the normal age in
      all adolescent patients. Head circumference: it was below the 3rd percentile in 7
      of 73 (9.6%), between the 3rd and the 25th percentiles in 36 of 73 (49.3%)
      patients, between the 25th and the 75th percentiles in 20 of 73 (27.3%) patients,
      and between the 75th and the 97th percentiles in 10 of 73 (13.7%) patients. Bone
      age: mean +/- SD bone age was -0.25 +/- 0.78 years. Comparisons: the only
      statistically significant correlation was that between the presence of feeding
      difficulties and underweight. CONCLUSION: Auxological parameters of children with
      del22q11 are characterized by: (1) weight deficiency in the first years of age,
      (2) weight normalization in the following years, (3) development of obesity in
      adolescence, (4) short stature in 10% of the patients, (5) normal height in
      adolescents, (6) slight delay in bone age in infancy, (7) microcephaly in 10% of
      the patients.

PMID- 11339375
TI  - Neuropsychological profile of children and adolescents with the 22q11.2
      microdeletion.
AB  - PURPOSE: Patients with one of the 22q11.2 deletion syndromes provide a unique
      opportunity to research the interface between genetics and brain-behavior
      relationships. This study investigates the neuropsychological characteristics and
      behavioral phenotype of children with this deletion syndrome. METHODS: We report
      updated findings from descriptive and nonparametric analyses of
      neuropsychological data from 80 children with the 22q11.2 deletion. RESULTS: The
      subjects showed higher verbal than nonverbal IQ scores, assets in verbal memory,
      and deficits in the areas of attention, story memory, visuospatial memory,
      arithmetic performance relative to other areas of achievement, and psychosocial
      functioning. CONCLUSION: Children with 22q11.2 deletion syndromes exhibit a
      behavioral phenotype reflective of nonverbal learning disabilities, concomitant
      language deficits, and social-emotional concerns.

PMID- 11339376
TI  - Taking advantage of early diagnosis: preschool children with the 22q11.2
      deletion.
AB  - PURPOSE: The purpose of this study is to review the neurodevelopmental outcome of
      infants and preschoolers with a 22q11.2 microdeletion and to discuss the our
      clinical observations of clinical implications for educational and therapeutic
      interventions. METHODS: One hundred twelve children (4 to 70 mos) with the
      22q11.2 deletion were assessed using standardized tests (Bayley Scales of Infant
      Development-II, Preschool Language Scales, Wechsler Preschool and Primary Scales
      of Intelligence-Revised). RESULTS: Fifty-four percent of the children were
      significantly delayed, 24% had mild delay, 22% had average cognitive development,
      and 80% were below average in language development. Delays are not explained by
      cardiac defects or palatal defects. CONCLUSION: Developmental delays, mild
      hypotonia, language and speech delays, and feeding disorders are common, and this
      finding indicates the need for early intervention services beginning in infancy
      for children with the 22q11.2 deletion.

PMID- 11339377
TI  - Anatomic patterns of conotruncal defects associated with deletion 22q11.
AB  - PURPOSE: Patients with cardiovascular malformations (CVMs) and deletion 22q11
      from our series were studied in order to (1) analyze the association with
      dysmorphic features and noncardiac anomalies, (2) identify specific cardiac
      patterns and the distinctive association with additional CVMs. METHODS: From 1993
      to 2000, 931 patients with CVM (95 with a clinical diagnosis of
      DiGeorge/velocardiofacial syndrome (DG/VCFS), 208 with different genetic
      syndromes, 628 without dysmorphic features) underwent accurate cardiac
      assessment, clinical and phenotypical examination, and screening for deletion
      22q11 by fluorescence in situ hybridization (FISH). RESULTS: Deletion 22q11 was
      detected in 88 of the total patients, and in 87 of the 95 patients with a
      clinical diagnosis of DG/VCFS. Only one patient among the 628 without dysmorphic
      features had deletion 22q11. Conotruncal heart defects were the most common CVMs,
      often presenting in association with additional anomalies in four areas of the
      cardiovascular system: (1) the aortic arch can be right sided, cervical, double,
      and the subclavian artery can be aberrant, (2) the pulmonary arteries can present
      discontinuity, diffuse hypoplasia, discrete stenosis, defect of arborization and
      major aortopulmonary collateral arteries (MAPCA), (3) the infundibular septum can
      be malaligned, hypoplastic, or absent, (4) the semilunar valves can be bicuspid,
      severely dysplastic, insufficient, or stenotic. CONCLUSION: In subjects with
      deletion 22q11 CVM is virtually always associated with one or more noncardiac
      anomalies. Deletion 22q11 is exceptionally rare in children with nonsyndromic
      CVMs. Specific patterns of CVMs are observed in patients with deletion 22q11,
      including (1) anomalies of the aortic arch, (2) anomalies of the pulmonary
      arteries and of the pulmonary blood supply, (3) defects of the infundibular
      septum, (4) malformations of the semilunar valves. These additional CVMs may
      influence the surgical treatment of these patients.

PMID- 11339378
TI  - Functional brain imaging study of mathematical reasoning abilities in
      velocardiofacial syndrome (del22q11.2).
AB  - PURPOSE: Children with velocardiofacial syndrome (VCFS) often have deficits in
      mathematical reasoning. Previous research has suggested that structural
      abnormalities in the parietal lobe region might underlie these deficits. The
      present study utilized functional magnetic resonance imaging (fMRI) to explore
      the relationship between brain function and mathematical performance in VCFS.
      METHODS: Eight children with VCFS and eight comparison subjects underwent fMRI
      scanning and completed an arithmetic computation task. RESULTS: In the VCFS
      group, increased activation was observed in the left supramarginal gyrus (LSMG)
      as the task difficulty increased. CONCLUSION: Aberrant LSMG activation, possibly
      due to structural deficits of the left parietal lobe, may explain decrements in
      arithmetic performance observed in VCFS.

PMID- 11339379
TI  - Tetralogy of Fallot associated with chromosome 22q11.2 deletion in adolescents
      and young adults.
AB  - PURPOSE: To clarify the clinical profiles of adolescents and young adults with
      tetralogy and 22q11.2 deletion, which has recently been identified as a cause of
      tetralogy of Fallot in about 15% of patients. METHODS: Thirty-four patients with
      22q11.2 deletion and tetralogy of Fallot, with or without pulmonary atresia,
      including 15 males and 19 females, with their age ranging from 16 to 35 years
      (mean = 25) were studied. Main outcome measurements include chromosome deletion
      identified by fluorescence in situ hybridization (FISH) of peripheral blood
      lymphocytes, medical states assessed with New York Heart Association
      classification, social activity assessed with Warnes index, IQ assessed by
      Wechsler test. RESULTS: Eighteen of 20 patients with tetralogy and pulmonary
      stenosis had cardiac repair, and their cardiac conditions were good except one.
      Of 14 patients with tetralogy with pulmonary atresia, 7 had Rastelli type cardiac
      repair and were doing well, although 4 of them needed re-operation for conduit
      stenosis. No cardiac repair was done in the other 7 patients with tetralogy,
      pulmonary atresia and major collateral arteries because their peripheral
      pulmonary arteries were too small. In 28 of the 34 patients (82%), overall social
      activity was limited because of extracardiac diseases, including deafness, club
      feet, mental retardation, and schizophrenia. The IQ in 17 patients was 59 +/- 13
      (mean +/- SD): range 41 to 79. In two patients, repeated IQ study showed a
      decrease. Four patients developed schizophrenia. CONCLUSION: Tetralogy with 22q11
      deletion can be repaired surgically except in those patients with pulmonary
      atresia, major collateral arteries, and small peripheral pulmonary arteries.
      However, most of the adult patients show an inability to function in social life
      in contrast to most patients with tetralogy but without the deletion, who have a
      normal social life. Extracardiac diseases, including deafness, club feet, mental
      retardation, and schizophrenia were major handicaps limiting full social
      activities in postoperative adolescents and young adults with 22q11.2 deletion
      and tetralogy.

PMID- 11339380
TI  - Evolutionarily conserved low copy repeats (LCRs) in 22q11 mediate deletions,
      duplications, translocations, and genomic instability: an update and literature
      review.
AB  - Several constitutional rearrangements, including deletions, duplications, and
      translocations, are associated with 22q11.2. These rearrangements give rise to a
      variety of genomic disorders, including DiGeorge, velocardiofacial, and
      conotruncal anomaly face syndromes (DGS/VCFS/CAFS), cat eye syndrome (CES), and
      the supernumerary der(22)t(11;22) syndrome associated with the recurrent
      t(11;22). Chromosome 22-specific duplications or low copy repeats (LCRs) have
      been directly implicated in the chromosomal rearrangements associated with
      22q11.2. Extensive sequence analysis of the different copies of 22q11 LCRs
      suggests a complex organization. Examination of their evolutionary origin
      suggests that the duplications in 22q11.2 may predate the divergence of New World
      monkeys 40 million years ago. Based on the current data, a number of models are
      proposed to explain the LCR-mediated constitutional rearrangements of 22q11.2.

PMID- 11339381
TI  - 22q11.2 microdeletions in adults with familial tetralogy of Fallot.
AB  - PURPOSE: To determine the incidence of 22q11.2 microdeletions in the adult
      survivors of correction of tetralogy of Fallot who have familial congenital heart
      disease. METHODS: Patients who had survived a correction of tetralogy of Fallot
      between 1954 and 1974 and had affected family members were identified during a
      study of these long-term survivors. Fluorescence in situ hybridization analysis
      was performed using both the N 25 (Oncor) and TUPLE1(VYSIS) probes, mapped to
      22q11.2. RESULTS: One of 18 (5.6%) patients had a microdeletion within 22q11.2,
      including both N25 and TUPLE1. CONCLUSION: 22q11.2 microdeletions involving
      TUPLE1 and/or N25 are present in a minority of adults with familial tetralogy of
      Fallot.

PMID- 11339382
TI  - Prenatal diagnosis of 22q11.2 deletion when ultrasound examination reveals a
      heart defect.
AB  - PURPOSE: The incidence of 22q11.2 deletion syndrome is approximately 1 in 5,000
      births, and accounts for 5-30% of all heart defects, making it one of the more
      common genetic conditions in the population. METHODS: We employed fluorescence in
      situ hybridization (FISH) to study the incidence of 22q11.2 deletions in fetuses
      with cardiac anomalies detected on ultrasound examination. RESULTS: Of 64 cases,
      18 had visible chromosome anomalies. FISH testing for 22q11.2 deletion was
      performed on the remaining 46 cases, and five exhibited a 22q11.2 deletion. Three
      of the five had de novo deletions, one was maternally inherited, and one family
      declined testing. CONCLUSION: FISH analysis for 22q11.2 deletion should be
      performed on all fetuses with cardiac defects (excluding hypoplastic left heart
      and echogenic focus) and a normal G-banded karyotype.

PMID- 11339383
TI  - Communication issues in 22q11.2 deletion syndrome: children at risk.
AB  - PURPOSE: The purpose of this investigation is to describe the communication
      profile of children with the 22q11.2 deletion syndrome from infancy through
      school age and to examine the influence of other medical aspects, such as palate
      anomalies, learning disorders, and cardiac defects of the syndrome to
      communication. METHODS: Seventy-nine children were examined using standardized
      tests of speech and language and perceptual measures of resonance and voice.
      RESULTS: Results show significant delay in emergence of speech and language
      milestones with delay/disorder in speech-language processes persisting into the
      school aged years, including those children diagnosed with nonverbal learning
      disabilities. Persistent articulation and resonance disorders were also present,
      presumed to be related in part to palatal anomalies. No correlation was found
      between cardiac status, learning disorders, palate anomalies and communication
      disorders. CONCLUSION: The need for early identification and management of
      communication skills is crucial in the care of children with the 22q11.2
      deletion.

PMID- 11339384
TI  - Profiles of communication disorder in children with velocardiofacial syndrome:
      comparison to children with Down syndrome.
AB  - PURPOSE: To describe communication profiles in children with velocardiofacial
      syndrome (VCFS) compared with children with Down syndrome. METHODS: Four children
      with VCFS and four children with Down syndrome underwent cognitive and speech and
      language assessment. RESULTS: Communication profiles of children with Down
      syndrome showed a flat profile, indicating all measures were similar and delayed
      relative to chronological age. Children with VCFS showed vocabulary, pattern of
      sound types, and Mean Babbling Length below cognitive and other language ages.
      CONCLUSION: Communication profiles of children with VCFS differed qualitatively
      and quantitatively from children with Down syndrome and support the hypothesis
      that some children with VCFS present with a profile of communication impairment
      that may be distinctive to the syndrome.

PMID- 11339385
TI  - Neuropsychiatric disorders in the 22q11 deletion syndrome.
AB  - PURPOSE: This study was undertaken with a view to establishing the occurrence of
      neuropsychiatric disorders in the 22q11 deletion syndrome. METHODS: Thirty-two
      children and young adults with genetically confirmed 22q11 deletion were given
      comprehensive neuropsychiatric assessments. RESULTS: Altogether, 56% had a
      neuropsychiatric disorder. Only 6% were of normal IQ and free of physchiatric
      disorder. Attention-deficit/hyperactivity disorder was diagnosed in 44% and 31%
      had an autism spectrum problem. In 16% criteria for both these diagnoses were
      met. Fifty-three percent had mental retardation, often with a test-profile
      suggesting a nonverbal learning disorder. CONCLUSION: The findings imply that a
      majority of children and adolescents with 22q11 deletion syndrome are in need of
      neuropsychiatric assessment and intervention.

PMID- 11339386
TI  - Rethinking the role of urinary magnesium in calcium urolithiasis.
AB  - BACKGROUND AND PURPOSE: The role of magnesium in urinary stone formation remains
      undefined. In vivo, magnesium inhibits stone formation in hyperoxaluric rats, and
      small clinical studies suggest a protective effect of magnesium supplementation
      in calcium oxalate stone formers. We performed a retrospective review of more
      than 7,000 stone patients to see if there is a relation between urinary magnesium
      and other stone risk variable constituents. MATERIALS AND METHODS: A national
      database of stone formers categorized by residential ZIP code was queried, and,
      using strict inclusion criteria, 2,147 patients having pure calcium oxalate
      stones were identified. There were 1,912 (89%) eumagnesuric (43-246 mg/24 hours)
      and 235 (11%) hypomagnesuric (<43 mg/24 hours) patients. RESULTS: Patients with
      decreased urinary magnesium excretion had significantly less daily urine
      excretion of citrate, calcium, oxalate, uric acid, and sodium than the
      eumagnesuric group (p < 0.0001). Stone recurrence was slightly more common in the
      hypomagnesuric group, although the difference was not statistically significant.
      The percentage of patients voiding <1 L of urine per day was significantly higher
      in the hypomagnesuric group. In the eumagnesuric group, males outnumbered females
      2:1, whereas hypomagnesuric patients showed a female predominance of 1.4:1.
      CONCLUSION: The beneficial effects of urinary magnesium on stone formation may be
      less than previously reported. The role of oral magnesium supplementation and the
      subsequent increase in urinary magnesium in calcium urinary stone formation
      remains unknown. Our data suggest that its effect on or interaction with citrate
      may be influential on urinary citrate concentrations. If magnesium has a
      protective effect, it may work through pathways that enhance citrate excretion.

PMID- 11339387
TI  - Extracorporeal shockwave lithotripsy in patients treated with antithrombotic
      agents.
AB  - PATIENTS AND METHODS: Between January 1996 and December 1999, 749 patients
      underwent electromagnetic SWL. Among them, 23 patients, 19 with renal and 4 with
      ureteral stones, were receiving antithrombotic drugs (aspirin, ticlopidine,
      dipyridamole). According to the cardiologist and hematologist, we divided these
      patients into two groups: Group 1 had a low thromboembolic risk (previous
      myocardial infarction), and Group 2 had a high thromboembolic risk (aortocoronary
      bypass, atrial fibrillation, cerebrovascular disease, peripheral occlusive
      arterial disease). Group 1 patients discontinued their antiplatelet therapy 8
      days prior to SWL to permit a sufficient number of functioning platelets to
      remain. Group 2 patients suspended antiplatelet therapy, and unfractioned heparin
      5000 IU tid (8 a.m., 4 p.m., and 12 p.m.) was administered for the 8 days prior
      to SWL. On the ninth day of withdrawal, SWL was performed in all patients. Close
      follow-up was performed during the postoperative period (hemoglobin, hematocrit,
      kidney ultrasonography, plain abdominal film). The antithrombotic therapy was
      restored in all patients within 10 to 14 days of withdrawal. RESULTS: Hematomas
      and thromboembolic events were not observed. At 3 months' follow-up, 14 patients
      (61%) were stone free, 3 (13%) had <4-mm fragments, and 6 (26%) had >4-mm
      residual fragments. CONCLUSION: Our schedules for the suspension or substitution
      of antithrombotic therapy, although tested in a small number of patients, allowed
      us to perform SWL without hemorrhagic or thromboembolic complications.

PMID- 11339388
TI  - Electrode performance beyond the manufacturer's recommended lifespan using the
      Dornier MFL 5000 lithotripter.
AB  - BACKGROUND AND PURPOSE: Electrodes used by the Dornier MFL 500 lithotripter have
      a specified lifespan, after which, the manufacturer recommends replacing the
      electrode before continuing the treatment. The aim of this study was to
      investigate whether electrodes continue to function effectively beyond 100%
      consumption by measuring the pressure output of electrodes up to 300% consumption
      or until electrode failure. MATERIALS AND METHODS: We assessed new, refurbished,
      and twice-refurbished electrodes to compare their respective performances.
      RESULTS: Rather than a decrease, there was a trend toward increased pressure
      output beyond 100% electrode consumption, with no drop in pressure prior to 300%
      consumption or electrode failure. All three types of electrodes functioned
      adequately above 100% consumption. CONCLUSION: These observations suggest that
      discarding the electrode before the completion of the treatment or electrode
      failure is not warranted. Using a single electrode rather than multiple
      electrodes to complete a treatment has the potential to save both time and cost.

PMID- 11339389
TI  - Controversial cases in endourology.

PMID- 11339390
TI  - Laparoscopic orchidopexy in children.
AB  - BACKGROUND: Cryptorchidism is a common condition in boys. Approximately 20% of
      undescended testes are nonpalpable and may be located within the abdominal
      cavity. Given the potential of these gonads for malignant transformation and
      infertility, it is essential to determine the presence or absence of a
      nonpalpable testis. METHODS: Radiologic imaging and open surgical exploration
      have proved to be unreliable. In the hands of experienced surgeons, laparoscopy
      has become the method of choice for evaluating the nonpalpable testis. RESULTS
      AND CONCLUSION: An increasing number of surgeons are applying laparoscopy in the
      treatment of nonpalpable testes, and early results are encouraging. Both
      diagnostic and therapeutic laparoscopy necessitate operative skills. The exact
      advantages of laparoscopy over conventional surgery in orchidectomy and single-
      or two-stage orchidopexy need to be determined.

PMID- 11339391
TI  - A perspective on laser lithotripsy: the fragmentation processes.
AB  - This paper describes in simple terms the physics of laser-calculus interactions
      and introduces a method with which physicians can understand or evaluate the
      application of any new laser technique for use in lithotripsy or other medical
      fields. Tissue optical properties and laser parameters govern the mechanism(s) of
      fragmentation of urinary or biliary calculi. Laser pulse energies for clinical
      lithotripsy range from Q0 = 20 mJ to 2 J for short-pulsed lasers to long-pulsed
      lasers, respectively. Lasers with short pulse durations (i.e., less than a few
      microseconds) fragment calculi by means of shockwaves following optical breakdown
      and plasma expansion of ionized water or calculus compositions or by cavitation
      collapse, thus manifesting a photoacoustical effect. Laser-tissue interactions
      involving dominant photomechanical or photoacoustical effects are usually stress
      confined. Long-pulsed lasers (i.e., >100 microsec), on the other hand, generate
      minimal acoustic waves, and calculi are fragmented by temperatures beyond the
      thresholds for vaporization of calculus constituents, melting, or chemical
      decomposition.

PMID- 11339392
TI  - Transperitoneal laparoscopic adrenalectomy: experience in 72 procedures.
AB  - PURPOSE: To evaluate the safety and effectiveness of transperitoneal laparoscopic
      adrenalectomy for a variety of adrenal diseases. PATIENTS AND METHODS: Seventy
      two patients underwent laparoscopic adrenalectomy from January 1995 until March
      1999. The indications for the treatment were limited to either functioning or
      nonfunctioning adrenal masses without radiologic evidence of involvement of the
      surrounding tissues. The indication for bilateral adrenalectomy was Cushing's
      disease after the failure of other therapies or Cushing's syndrome secondary to
      ectopic ACTH secretion without the discovery of a primary neoplasm. RESULTS:
      Thirty-five of the adrenalectomies were performed on the left side and 33 on the
      right side, and 4 were performed bilaterally. The right-sided procedures required
      a mean operating time of 130 minutes (range 85-200 minutes), the left-sided
      procedures required a mean operating time of 140 minutes (range 95-200 minutes),
      and the bilateral procedures required a mean operating time of 240 minutes (range
      210-290 minutes). A conversion from laparoscopy to laparotomy was necessary for 3
      patients (4%). Intraoperative complications were reported in 6 patients (8%).
      Postoperative complications likewise occurred in six patients. CONCLUSIONS: These
      procedures proved to be safe and able to remove the majority of either
      functioning or nonfunctioning benign adrenal masses. Some controversy remains
      regarding the safety of laparoscopic adrenalectomy for large lesions and the
      safety of bilateral laparoscopic adrenalectomy because of bleeding risks,
      anesthetic risks, and long operative times. The effectiveness of laparoscopic
      adrenalectomy for nonfunctioning adrenal masses with histologic findings of
      carcinoma has not yet been proved.

PMID- 11339393
TI  - Successful conservative management of nephrocolic fistula.

PMID- 11339394
TI  - Percutaneous ureterolithotomy: direct method for removal of impacted ureteral
      stones.
AB  - PURPOSE: We report 52 percutaneous urterolithotomies in 51 patients having large,
      impacted middle ureteral stones. Direct percutaneous stone removal can be
      performed as successfully as in cases of renal stones treated with percutaneous
      nephrolithotomy. METHODS: The operation is performed under local anesthesia;
      therefore, the procedure is quicker and simpler than the laparoscopic or
      retroperitoneoscopic intervention. All patients became stone free. In two
      patients (4%), ultrasound disintegration was necessary; in the remaining cases,
      there was no need for any fragmentation: the stone was removed intact. A
      retroperitoneal drain was always left at the end of the procedure. With the
      exception of two cases, the ureter was always stented without closure of the
      ureteral incision. RESULTS: Fever (> or = 38 degrees C) was observed in 15
      patients (29%) for 2 days. Retroperitoneal hematoma 5 cm in diameter was seen in
      one patient. One patient had urine leakage through the retroperitoneal drain in
      the postoperative period for 18 days. Also, one patient came back 3 days after
      discharge with urine leakage through the percutaneous retroperitoneal tract.
      CONCLUSION: Direct percutaneous ureterolithotomy is an effective way to remove
      impacted middle ureteral stones but is advisable only for endourologists with
      considerable experience.

PMID- 11339395
TI  - Retroperitoneoscopic ureterolysis and reconstruction of retrocaval ureter.
AB  - We report a case of circumcaval ureter in a symptomatic young man who was managed
      successfully by retroperitoneoscopic ureterolysis and ureteroureteral
      reconstruction using three-port technique.

PMID- 11339396
TI  - Ureteroscopic decompression of an unusual uroepithelial cyst using the
      holmium:YAG laser.
AB  - We report a case of an unusual uroepithelial cyst arising from a renal calix in
      an African-American man with sickle cell trait. The lesion was incised and
      decompressed using a 7.5F flexible ureteroscope in conjunction with the
      holmium:YAG laser and a 200-microm quartz laser fiber. To our knowledge,
      endourologic management of this type of lesion has not been described in the
      literature.

PMID- 11339397
TI  - Comparison of symptoms related to positioning of double-pigtail stent in upper
      pole versus renal pelvis.
AB  - PURPOSE: This study was a comparison of the symptomatology associated with
      placement of the upper coil of a double-pigtail stent in the upper pole or the
      renal pelvis. PATIENTS AND METHODS: A prospective study with 40 patients was
      performed. In 20 patients, the stent was placed in the upper pole (Group A) and
      in another 20 patients (Group B) in the renal pelvis. A questionnaire was
      addressed to all patients before the removal of the stent concerning the presence
      and severity of flank pain (using a standardized 10-point scale), the presence
      and severity of urinary urgency (using a standardized 10-point scale), the
      presence of dysuria, and quality of life with the stent in place. RESULTS: Flank
      pain was present in 17 (85%) and 15 (75%) patients in Groups A and B,
      respectively. The average severity of flank pain was 4.3 (range 0-7) and 4.5
      (range 0-10) in Group A and B, respectively (p = 0.764). Urinary urgency was
      present in 13 (65%) and 15 (75%), patients in Group A and B, respectively. The
      average severity of urgency was 3.1 (range 0-7) and 5.3 (range 0-10) in Group A
      and B, respectively (p = 0.037). Dysuria was present in 4 (20%) and 13 (65%), and
      the average quality of life score was 2.5 and 3.05 in Group A and B, respectively
      (p = 0.04). CONCLUSION: Positioning of the proximal end of the double-pigtail
      stent in the upper pole of the kidney appears to be better tolerated by patients
      than is the standard insertion in the renal pelvis.

PMID- 11339398
TI  - In vitro bactericidal effect of a modified thermal Nitinol electrode.
AB  - PURPOSE: A standard electrode surgical generator connected to a Nitinol coil was
      used in vitro to evaluate whether the generated electromagnetic energy had any
      bactericidal effect on Escherichia coli. MATERIALS AND METHODS: The ATCC 259222
      E. coli strain was used. We mixed 135 mL of a 1.5% non-nutritive agar with 15 mL
      of a 10(6) CFU/mL inoculum and transferred it to gas-sterilized plastic
      containers lined with aluminium foil. A 22F cylindrical shape was cut from the
      center of the agar, and a Nitinol coil was placed in that space and connected to
      a standard electrode surgical generator. Electrical energy was then applied from
      5 to 25 V at 5-V increments. Temperatures were measured with two thermocouples
      placed in the middle and periphery of each agar. The treatment was stopped when
      the temperature at the middle thermometer reached 50 degrees C. The control group
      was not treated and was embedded in a water bath at 45 degrees C. Three 3 x 7-mm
      pieces were sliced from the inner to the outer part of the agar and processed,
      and colony counts were performed. RESULTS: We observed statistically significant
      deleterious effects on E. coli in all three zones when the treatment voltage was
      15 and 20. When the potential was raised to 25 V, we observed a significant
      result only in the core zone. The treatment duration was 50 minutes for 5 and 10
      V, 45 minutes for 15 V, 15 minutes for 20 V, and 10 minutes for 25 V. CONCLUSION:
      The bactericidal effect was mainly in the central area, decreasing linearly
      toward the periphery, and was related to the temperature reached during
      activation of the electrical generator. These results were disappointing with
      regard to the utility of Nitinol stents to treat bacterial prostatitis.

PMID- 11339399
TI  - Laparoscopic partial nephrectomy in the pig: comparison of three hemostasis
      techniques.
AB  - BACKGROUND AND PURPOSE: Control of intraoperative bleeding is the main technical
      difficulty encountered during laparoscopic partial nephrectomy. The objective of
      this study was to compare the efficacy and morbidity of three renal parenchymal
      hemostasis techniques: high-frequency bipolar electrical current, high-frequency
      unipolar spray electrical current, and ultrasound during laparoscopic partial
      nephrectomy performed in pigs without vascular control. MATERIALS AND METHODS: A
      standardized laparoscopic transperitoneal right lower-pole partial nephrectomy
      was performed in 27 pigs with a mean weight of 65 +/- 5 kg. The pigs were divided
      into three groups according to the technology used: Group 1 = bipolar electrical
      current, Group 2 = unipolar spray electrical current, and Group 3 = ultrasound.
      Intravenous urography was performed on the 28th day. The kidneys were then
      removed for histologic examination, and the pigs were sacrificed. The criteria
      evaluated were intraoperative and postoperative complications, blood loss, renal
      function, and thickness of the parenchymal lesions induced. The Kruskal-Wallis
      nonparametric test for comparison of medians was used for statistical analysis of
      the data (P < 0.05). Data from pigs that died before the end of the study were
      excluded from the analysis. RESULTS: All partial nephrectomies were performed
      laparoscopically, and all pigs were alive at the end of the operation. The
      postoperative complication rate was 11% (N = 3): two pigs died before the end of
      the study, one from hemorrhage on Day 6 (Group 2), and the other from prolonged
      reflex ileus with sacrifice of the pig on Day 7 (Group 3). One pig developed an
      asymptomatic urinoma (Group 2). Blood loss was significantly lower when
      ultrasound was used (P = 0.026). Global renal function was not significantly
      altered in the various groups. The median thickness of tissue necrosis and
      fibrosis detected in the scar zone was 6 mm (range 4-10 mm) and was similar in
      the three groups. CONCLUSION: Partial nephrectomy can be performed by laparoscopy
      without vascular control in the pig. Coagulation by ultrasound appears to present
      an advantage in terms of limitation of blood loss compared with coagulation by
      bipolar or unipolar spray electrical currents without presenting any benefit in
      terms of preservation of the renal parenchyma.

PMID- 11339400
TI  - Electrovaporization of the prostate with the Gyrus device.
AB  - PURPOSE: To assess the efficacy and the safety of a new transurethral endoscopic
      device using bipolar electrocautery, the Gyrus system. This system permits rapid
      prostate tissue removal by endoscopic vaporization with little bleeding and no
      pad return using saline irrigation and therefore eliminating TURP syndrome.
      PATIENTS AND METHODS: Forty-two patients (mean age 70; range 49-90 years) with
      symptomatic benign prostatic hyperplasia (BPH) without suspected cancer,
      confirmed by digital rectal examination and PSA tests, were treated between
      October 1998 and February 1999 with the Gyrus and evaluated at 1 and 3 months
      postoperatively by the International Prostate Symptom Score (IPSS) and maximum
      urinary flow rate. RESULTS: No postoperative bleeding necessitating
      catheterization for postoperative retention occurred. The duration of the
      procedure was < or = 30 minutes in 12 patients, 30 to 60 minutes in 27 patients,
      and >60 minutes in 3 patients. The mean time of postoperative continuous bladder
      irrigation was 1.2 days (0.5-3 days). The mean catheterization time was 1.4 days
      (range 0.5-5 days). Urethral stricture requiring treatment occurred in two
      patients. Dysuria was reported by four patients (mild two, severe two). The
      postoperative hospitalization was a mean of 2.2 days. The mean peak flow rate
      increased from 7.9 to 19.7 mL/sec at 3 months, and the IPSS decreased from 16 to
      9 at 3 months. CONCLUSION: Our preliminary results with a bipolar electrode for
      electrovaporization of the prostate using the Gyrus suggest that it is a useful
      and safe endoscopic device. It appears to be an effective treatment for BPH;
      however, long-term results (i.e., 1-year follow-up) should be evaluated. This
      pilot series permits a comparative study with TURP to assess the benefits for
      patients and the health care system.

PMID- 11339401
TI  - Randomized study of transurethral resection of the prostate and combined
      transurethral resection and vaporization of the prostate as a therapeutic
      alternative in men with benign prostatic hyperplasia.
AB  - BACKGROUND AND PURPOSE: In recent years, various minimally invasive alternatives
      to transurethral resection have become available for treatment of benign
      prostatic hyperplasia (BPH). Transurethral electrovaporization has become
      popular, with reported improvements in subjective and objectives measures, but a
      high rate of postoperative irritative symptoms and lack of tissue for histologic
      examination are the two most commonly reported disadvantages of this procedure.
      To decrease the postoperative irritative symptoms while minimizing intraoperative
      and postoperative bleeding and also to obtain tissue samples, we have combined
      the techniques of vaporization, which was termed "vapor-cut." The aim of this
      randomized study was to compare the efficacy and safety of vapor-cut with those
      of the gold standard, transurethral resection. PATIENTS AND METHODS: A series of
      100 consecutive men (mean age 63.5 +/- 3.4 years) with moderate to severe
      symptoms of prostatism were randomized to receive transurethral resection of the
      prostate (TURP) or vapor-cut since November 1997. Adverse events during the
      procedure, including serial changes in both serum hematocrit and sodium and
      postoperative irritative symptoms, were recorded after removal of the urethral
      catheter. Preoperative and postoperative symptom scores and maximum flow rates
      (Qmax) were obtained from all patients. The volume of the prostate was measured
      preoperatively and postoperatively using transrectal ultrasonography. The mean
      follow-up of the patients was 6.7 months (range 6-10 months). RESULTS: The mean
      operative times for the vapor-cut group and the TURP group were 48.2 minutes and
      42.7 minutes, respectively (P > 0.05). In the TURP group and the vapor-cut group,
      the International Prostate Symptom Score (I-PSS) decreased from 21.6 to 5.0 (P <
      0.01) and from 19.4 to 4.0 (P < 0.01), respectively, at 6 months. The Qmax
      increased from 9.2 +/- 2.6 mL/sec to 24.6 +/- 3.4 mL/sec (P < 0.01) in the TURP
      group and from 7.9 +/- 2.1 mL/sec to 26.7 +/- 3.7 mL/sec (P < 0.01) in the vapor
      cut group. The mean reductions in the weight of the prostate were 49.8% in the
      TURP group (P < 0.05) and 53.6% in the vapor-cut group (P < 0.05). Both
      catheterization time and hospital stay were significantly shorter for the vapor
      cut group (P < 0.05). The decreases in the mean serum sodium concentration were
      statistically insignificant in both groups. However, the decrease in the mean
      hematocrit was statistically significant in the TURP group but not in the vapor
      cut group. No patient in either group had the transurethral resection syndrome or
      required blood transfusion. After removal of the urethral catheter, irritative
      voiding symptoms, usually associated with frequency, were greater in those
      patients treated with TURP than in those having vapor-cut. None of the patients
      demonstrated sphincteric incontinence, bladder neck contracture, or urethral
      stricture. CONCLUSION: From our preliminary experience, vapor-cut seems to give
      results comparable to those of TURP. Because there is almost no bleeding during
      vapor-cut, the procedure is performed under excellent visibility, which permits
      more rapid and effective resection.

PMID- 11339402
TI  - Literature watch.

PMID- 11339403
TI  - Simulation of acid-base condition and copper speciation in the fish gill
      microenvironment.
AB  - pH, alkalinity, and mucus content in the fish gill microenvironment of carp
      (Cyprinus carpio) were measured by exposing fish to copper at various water pH
      levels using an apparatus which separates inspired and expired water. The
      relationship between pH levels inside and outside of the gill microenvironment,
      between pH and alkalinity, and between mucus secretion, pH, and copper exposure
      concentration were modeled. Copper speciation in the surrounding water and in the
      fish gill microenvironment was simulated using MINTEQA2 chemical equilibrium
      calculation software. The results of the modeling for pH, alkalinity, and mucus
      calculation were then adopted as inputs for purposes of parameter identification
      in the speciation modeling. The differences observed in the copper species
      distribution between that of the fish gill microenvironment and the surrounding
      water were based on the speciation modeling. The change in copper bioavailability
      for fish uptake was also examined. The results indicate the presence of an
      experimental pH balance point at 6.9, where the pH in the fish gill
      microenvironment is identical to that of the surrounding water. The observed
      deviation range in pH levels between that found at the gills and that of the
      surrounding water varied from -0.4 to 0.8 units. A sinusoidal model was developed
      for calculation of gill pH based on the pH of the surrounding water. Models
      calculating alkalinity either in the gill microenvironment or in the surrounding
      water and for estimating mucus secretion were also developed. The results of the
      chemical equilibrium calculations demonstrate that, within a pH range of 6-9, the
      dominant species of copper in bulk solution shifted from free ions to that of the
      hydroxo complex. With respect to the fish gill microenvironment, the dominant
      species found under acidic conditions were the mucus copper complex and free
      ions. Because of the influence of mucus complexation and pH change, bioavailable
      copper species in the fish gill microenvironment were significantly lower than
      that in the bulk solution, especially under acidic conditions.

PMID- 11339404
TI  - Improved convergence and speed for the distance geometry program APA to determine
      protein structure.
AB  - The alternating projections algorithm (APA) is a program that is based on
      alternating projections and is designed to determine the three dimensional
      structure of proteins using distance geometry. The sampling and convergence
      properties of APA, as tested on bovine pancreatic trypsin inhibitor (BPTI) were
      previously reported in this journal. The results confirmed the program's earlier
      success with poly-L-alanine. However, the asymptotic convergence of the
      alternating projections was slow. We show that after good convergence is first
      obtained via alternating projections, that a weighted quadratic penalty function
      then produces the final conformation with better convergence in half the time
      required by the asymptotic convergence of alternating projections.

PMID- 11339405
TI  - Characteristic substructures in sets of organic compounds with similar infrared
      spectra.
AB  - A method based on the determination of maximum common substructures is applied
      for the generation of substructures which are characteristic for a given set of
      molecular structures. The molecular structures are from hitlists obtained by
      spectral library searches; the hitlists contain those reference compounds, which
      have infrared spectra most similar to that from the query compound. The
      influences of various parameters of this method are investigated with the aim to
      improve the relevance of the obtained substructures for the structure of the
      query compound.

PMID- 11339406
TI  - Simultaneous quantitative UV spectrophotometric determination of multicomponents
      of amino acids using linear neural network.
AB  - Simultaneous determination of multicomponents of six amino acids with a novel
      chemometric technique-a linear neural network (LNN) algorithm is reported in this
      study. Based on the data correlation coefficient and standard deviation method,
      17 representative wavelength points are selected from the original UV spectral
      data (343 points) as the original input patterns for LNN to build a neural
      network model. The results obtained only by iterating 15 times is satisfying,
      with a correlation coefficient of 0.999 and a relative small standard deviation.

PMID- 11339407
TI  - Monte Carlo simulation towards ripple phase modelling.
AB  - We present a novel approach to analysis of the gel-fluid transition of lipid
      membrane. The method is based on the Pink's model but in contrast to its standard
      version the dipole character of the lipid molecules polar part is considered.
      Moreover, less constrained movement of entire molecules is allowed. Such an
      approach includes into the model conditions imposed by the adjacent medium such
      as ionic strength, pH, and other factors affecting biological membranes via the
      polar part. The results obtained contribute to the explanation of the ripple
      phase phenomenon.

PMID- 11339408
TI  - Modeling and prediction for discharge lifetime of battery systems using hybrid
      evolutionary algorithms.
AB  - A hybrid evolutionary modeling algorithm (HEMA) is proposed to build the
      discharge lifetime models with multiple impact factors for battery systems as
      well as make predictions. The main idea of the HEMA is to embed a genetic
      algorithm (GA) into genetic programming (GP), where GP is employed to optimize
      the structure of a model, while a GA is employed to optimize its parameters. The
      experimental results on lithium-ion batteries show that the HEMA works
      effectively, automatically and quickly in modeling the discharge lifetime of
      battery systems. The algorithm has some advantages compared with most existing
      modeling methods and can be applied widely to solving the automatic modeling
      problems in many fields.

PMID- 11339409
TI  - Dissipative exponentially-fitted methods for the numerical solution of the
      Schrodinger equation.
AB  - The first dissipative exponentially fitted method for the numerical integration
      of the Schrodinger equation is developed in this paper. The technique presented
      is a nonsymmetric multistep (dissipative) method. An application to the bound
      states problem and the resonance problem of the radial Schrodinger equation
      indicates that the new method is more efficient than the classical dissipative
      method and other well-known methods. Based on the new method and the method of
      Raptis and Allison (Comput. Phys. Commun. 14 (1978) 1-5) a new variable-step
      method is obtained. The application of the new variable-step method to the
      coupled differential equations arising from the Schrodinger equation indicates
      the power of the new approach.

PMID- 11339410
TI  - A modified Runge-Kutta method with phase-lag of order infinity for the numerical
      solution of the Schrodinger equation and related problems.
AB  - A modified Runge-Kutta method with phase-lag of order infinity for the numerical
      solution of the Schrodinger equation and related problems is developed in this
      paper. This new modified method is based on the classical Runge-Kutta method of
      algebraic order four. The numerical results indicate that this new method is more
      efficient for the numerical solution of the Schrodinger equation and related
      problems than the well known classical Runge-Kutta method of algebraic order
      four.

PMID- 11339411
TI  - Protein structure determination by non-parametric regression and knowledge-based
      constraints.
AB  - We have devised a non-parametric regression-based approach for the estimation of
      small- and medium-range inter-residual three-dimensional (3d) distances in a
      protein using only the primary sequence as input. A multivariate analysis of
      variance technique is used to identify the attributes of the primary sequence
      that is most effective in determining the tertiary structure. Certain compactness
      and hydrophobic core building heuristics are used along with the estimated
      distances in a distance geometry program to predict the 3d-structure (tertiary
      fold). Our method is found to predict correctly the native topologies of small
      proteins having up to 150 residues. The sensitivity of the structures to long
      range distance constraints is studied by incorporating a small number of NMR
      distance restraints. In terms of modularity, precision, accuracy and
      computational efficiency our method is found to be better in comparison with
      current computational methods like X-PLOR and DRAGON on the sample that was
      reported in the literature for the comparison of these two methods.

PMID- 11339412
TI  - Recognition of environmental and genetic effects on barley phenolic fingerprints
      by neural networks.
AB  - Through computational analysis of high-performance liquid chromatography (HPLC)
      traces we find correlations between secondary metabolites and growth conditions
      of six varieties of barley. Using artificial neural networks, it was possible to
      classify chromatograms for which the varieties were fertilized by nitrogen and
      treated by fungicide. For each variety of barley we could also differentiate it
      from the others. Surprisingly, all these classification tasks could be solved
      successfully by a simple network with no hidden units. When adding to the
      methodology pruning of the network weights, we were able to reduce the set of
      peaks in the chromatograms and obtain a necessary subset from which the growth
      conditions and differentiation may be decided. In some instances, more complex
      networks with hidden units could lead to a further reduction of the number of
      peaks used. In most cases, far more than half of the peaks are redundant. We find
      that it requires fewer information-rich peaks to perform the variety
      differentiation tasks than to recognize any of the growth conditions. Analysis of
      the network weights reveals correlations between weighted combinations of peaks.

PMID- 11339413
TI  - Antinuclear (chromatin) autoantibodies in autoimmune hepatitis.

PMID- 11339414
TI  - Apoptosis and liver diseases: recent concepts of mechanism and significance.
AB  - Apoptosis, or programmed cell death, is a highly conserved mechanism that plays
      an essential role in numerous normal developmental and regulatory processes and
      disease states. It is mediated by a variable interaction among several components
      of the cell, including cell surface death receptors, the caspase cascade,
      mitochondrial metabolism and energetics, and the cytoskeleton. Even in those
      instances in which cell surface death receptors play a role, mitochondria are
      often central to the process, not only in mediating the death program, but in
      initiating it as well. In regard to mitochondrial involvement, a key role is
      hypothesized for an interaction among AMP-activated protein kinase, cytoskeletal
      intermediate filaments, and mitochondrial oxidation of fatty acids. This proposed
      interaction may be a critical element in the pathogenesis of intramitochondrial
      oxidative stress, diminished inner membrane potential (delta psi(m)), and other
      mitochondrial changes that contribute to cell death. Apoptosis may participate in
      a wide variety of disease processes, ranging from chemical and physical injury to
      viral infection and cancer, but its mechanistic and functional relationship to
      these conditions remains incompletely understood. Despite this, an understanding
      of the mechanisms involved and of the identity of potential pharmacologic targets
      is increasing, and warrants an optimistic view of their potential for clinical
      application.

PMID- 11339415
TI  - Effect of mouth washing on the.
AB  - BACKGROUND: Mouth washing is often mentioned as a possible method to eliminate
      the interference of urease activity in the oral cavity before the [13C]-urea
      breath test (UBT). However, the effectiveness of mouth washing prior to testing
      has not been demonstrated clearly in the literature. Thus, the present study was
      designed to examine the consistency of the [13C]-UBT and the effects of mouth
      washing on it. METHODS: A total of 101 healthy volunteers underwent the [13C]-UBT
      three times. The first and second tests used a standard protocol and collected
      samples at 5, 10, 15 and 30 min. In the third test, the procedure was the same
      except that mouth washing was omitted. RESULTS: We used 5 permil (/1000) as the
      cut-off value and there were 21 (20.8%) positive cases. The kappa values for the
      samples collected at 5, 10, 15 and 30 min between the first and second tests were
      0.68, 0.97, 1 and 1, respectively, and all showed good consistency, except for
      the sample collected at 5 min. Judging from the mean value of the [13C]
      enrichment of the first and second tests (with mouth washing) and the third test
      (without mouth washing), 50 (63.3%), 15 (18.8%), 0 and 0 cases at 5, 10, 15 and
      30 min, respectively, changed from negative to positive. There were 14 (17.5%)
      and six (7.5%) cases at 15 and 30 min, respectively, whose [13C] enrichment
      changed from less than 3 (negative) to between 3 and 5 (border zone).
      CONCLUSIONS: These results indicate that mouth washing had an important effect on
      samples obtained at 5 and 10 min, while this influence decreased at 15 min and
      was lowest at 30 min.

PMID- 11339416
TI  - A randomized controlled comparison of three quadruple therapy regimens in a
      population with low Helicobacter pylori eradication rates.
AB  - BACKGROUND AND AIM: We sought to compare the efficacy and tolerability of an
      omeprazole/clarithromycin/bismuth/tetracycline-based quadruple therapy to that of
      a ranitidine/metronidazole/bismuth/tetracycline-based quadruple therapy of 2 or 3
      weeks duration in a population with a high prevalence of metronidazole-resistant
      Helicobacter pylori and low triple therapy eradication rates. METHODS: Two
      hundred and twenty-one patients who presented endoscopically proven duodenal
      ulcers and a positive rapid urease test were randomized to receive either: (i)
      omeprazole 20 mg b.i.d., clarithromycin 250 mg b.i.d., bismuth subcitrate 240 mg
      b.i.d. and tetracycline 500 mg b.i.d (OCBT) for 2 weeks; (ii) ranitidine 300 mg
      b.i.d., metronidazole 500 mg b.i.d, bismuth subcitrate 240 mg b.i.d. and
      tetracycline 500 mg b.i.d. (RMBT2) for 2 weeks; or (iii) ranitidine 300 mg
      b.i.d., metronidazole 500 mg b.i.d, bismuth subcitrate 240 mg b.i.d. and
      tetracycline 500 mg b.i.d. (RMBT3) for 3 weeks. Patients were interviewed 2 weeks
      after the completion of therapy to review compliance and side-effects.
      Eradication of H. pylori was assessed 8 weeks after the completion of therapy
      with the use of a 14C-urea breath test. RESULTS: The per-protocol eradication
      rate was significantly higher with OCBT (88%) than RMBT2 (73%) or RMBT3 (71%)
      (P<0.05). The intent-to-treat eradication rate was numerically higher with OCBT
      (80%) than RMBT2 (68%) or RMBT3 (68%), although this difference did not reach
      statistical significance (P=0.09). Per-protocol or intent-to-treat eradication
      rates were similar with RMBT2 and RMBT3. There were significantly greater side
      effects with the RMBT2 regimen. CONCLUSIONS: The
      omeprazole/clarithromycin/bismuth/tetracycline-based quadruple therapy provides
      higher H. pylori eradication rates than the
      ranitidine/metronidazole/bismuth/tetracycline-based quadruple therapy when
      administered per protocol. The prolongation of the latter regimen from 2 to 3
      weeks did not increase eradication rates.

PMID- 11339417
TI  - Effect of Helicobacter pylori eradication on gastric mucosal phospholipid content
      and its fatty acid composition.
AB  - BACKGROUND AND AIMS: Whether Helicobacter pylori eradication alters gastric
      mucosal phospholipid contents and their fatty acid composition remains unclear.
      The aim of the present study was to clarify the effect of H. pylori eradication
      on gastric mucosal phosphatidylcholine (PC) content and its fatty acid
      composition. METHODS: Endoscopic biopsy specimens were taken from the antrum and
      body of each of 19 asymtomatic male volunteers for detection of H. pylori,
      histopathological assessment of gastritis, phospholipid determination and fatty
      acid analysis. All the subjects with H. pylori infection were treated with
      eradication therapy. Endoscopy and tissue sampling were repeated again 1 and 6
      months after all treatment. RESULTS: In eight subjects, H. pylori infection was
      evident and was successfully eradicated. Pretreatment degrees of lymphocytes and
      plasma cells (inflammation) and polymorphonuclear neutrophils (activity) were
      greater in H. pylori-positive subjects compared with H. pylori-negative subjects
      (P<0.001), whereas the degree of inflammation decreased (P<0.001), and
      neutrophils had completely disappeared at 6 months after eradication. Moreover,
      the gastric mucosal PC contents at the antrum and body were unchanged within 1
      month after cessation of treatment, but increased at 6 months after eradication
      (P<0.05). At 6 months after cessation of treatment, H. pylori-eradicated subjects
      had an increase (+30% at antrum, +18% at body) in linoleic acid composition and a
      decrease (-37%, -43%) in arachidonic acid composition of PC at the antrum and
      body, respectively. CONCLUSIONS: These findings suggest that H. pylori
      eradication reduces the production of various eicosanoids, resulting in the
      normalization of gastric mucosal PC content and its fatty acid composition, which
      may consequently cause the gastric mucosal hydrophobicity to be normalized.

PMID- 11339418
TI  - Comparison of clinical, serological and histological findings between non-ulcer
      dyspepsia patients with and without Helicobacter pylori infection.
AB  - BACKGROUND AND AIMS: The role of Helicobacter pylori (H. pylori) infection in non
      ulcer dyspepsia (NUD) remains controversial. This study investigates the
      clinical, serological and histological differences between patients with H.
      pylori-positive and -negative NUD. METHODS: One hundred and eighty consecutive
      patients with NUD were enrolled from January to December 1998. The severity of
      symptoms was evaluated by the Tucci's scoring system. The histological changes of
      gastric mucosa were assessed according to the Updated Sydney System, and a
      fasting blood sample was obtained to test the serum gastrin and pepsinogen I
      levels. RESULTS: The H. pylori-positive NUD patients were notably older than H.
      pylori-negative NUD patients (48.2 +/- 15.9 vs 39.8 +/- 15.7 years, P= 0.001).
      There were no differences in other clinical factors between the two NUD groups.
      The serum pepsinogen I levels were considerably higher in H. pylori-positive NUD
      patients than in H. pylori-negative NUD patients (78.9 +/- 42.2 vs 61.5 +/- 43.3
      ng/mL, P<0.01). However, no significant differences in serum gastrin levels were
      discovered between the two groups. The antrum histological scores for chronic
      inflammation, acute inflammation, gland atrophy and lymphoid follicles were
      higher in H. pylori-positive NUD patients than in H. pylori-negative NUD patients
      (2.09 vs 1.01, P<0.001; 1.22 vs 0.36, P<0.001; 0.76 vs 0.36, P<0.01; 0.33 vs
      0.13, P<0.01, respectively). CONCLUSIONS: The present study discovered marked
      differences in age, serum pepsinogen I levels, histological grades of acute
      inflammation, chronic inflammation, gland atrophy and lymphoid tissue formation
      between H. pylori-positive and H. pylori-negative NUD patients. Further
      investigation of the clinical prognosis of the two groups of patients is
      necessary.

PMID- 11339419
TI  - Monochloramine impairs mucosal blood flow response and healing of gastric lesions
      in rats: relation to capsaicin-sensitive sensory neurons.
AB  - AIMS: We examined the effects of monochloramine (NH2Cl) on the gastric mucosal
      blood flow (GMBF) response and the healing of ethanol-induced gastric lesions in
      rats. METHODS: Rats fasted for 18 h were given the 99% ethanol p.o. for induction
      of gastric lesions, and were fed normally from 1 h later onwards. Monochloramine,
      at non-ulcerogenic doses (5 to approximately 20 mmol/L), was given p.o. twice
      daily for 7 days, starting 2 h after ethanol treatment. RESULTS: Gastric lesions
      caused by ethanol healed almost completely within 7 days with re
      epithelialization. The repeated administration of NH2Cl significantly delayed the
      healing of ethanol-induced gastric lesions in a dose-dependent manner. The
      damaged mucosa showed a marked rise in H+ permeability, resulting in luminal acid
      loss, but this process was accompanied by an increase of mucosal blood flow.
      Monochloramine did not affect the increased mucosal H+ permeability observed in
      the stomach after damage by ethanol, but significantly inhibited the mucosal
      hyperemic response associated with luminal acid loss. Prior exposure of the
      mucosa to NH2Cl (20 mmol/L) did not affect the gastric hyperemic response caused
      by mucosal application of misoprostol (a prostaglandin E1 derivative) or NOR-3 (a
      nitric oxide donor), but totally attenuated the increase of GMBF in response to
      intragastric capsaicin. Impaired healing and GMBF responses were also observed in
      rats following chemical ablation of capsaicin-sensitive sensory neurons.
      CONCLUSIONS: These results suggest that NH2Cl impaired the healing of acute
      gastric mucosal lesions at low concentrations, and this action may be
      attributable, at least partly, to the impairment of gastric hyperemic response
      caused by the dysfunction of capsaicin-sensitive sensory neurons.

PMID- 11339420
TI  - Diazoxide, a K(ATP) opener, accelerates restitution of ethanol or indomethacin
      induced gastric ulceration in rats independent of polyamines.
AB  - BACKGROUND AND AIMS: Experimental acute gastric ulcerations (EAGU) are healed
      very rapidly. This healing process has two steps; mucosal restitution and delayed
      repair. Adenosine 5'-triphosphate (ATP)-dependent potassium channels (K(ATP))
      have a regulatory role in the gastrointestinal physiology. In the present study,
      the effects of K(ATP) channel modulators; diazoxide (channel opener) and
      glibenclamide (channel antagonist) on the healing of EAGU were investigated. The
      effect of polyamine (mediators presumably responsible for restitution)
      biosynthesis by difluoromethylornithine (DFMO) on diazoxide-induced alterations,
      and the effects of acid secretion inhibitors (cimetidine, omeprazole and
      atropine) on the mucosal restitution of EAGU were also studied. METHODS: Groups
      of 10 male rats were starved for 24 h and EAGU was induced by oral administration
      of 1 mL 60% ethanol or a subcutaneous injection of 30 mg/kg indomethacin.
      Different groups were subjected to various doses of diazoxide (5, 15, 45 mg/kg)
      and/or glibenclamide (2, 6, 18 mg/kg) administered intraperitoneally (i.p.) after
      EAGU induction. Polyamine biosynthesis was inhibited by a single i.p. injection
      of DFMO (500 mg/kg), administered 10 min before EAGU induction. Cimetidine,
      omeprazole or atropine were administered intraperitoneally at doses of 200, 5 and
      1 mg/kg, respectively, after EAGU induction. Animals were killed and their
      gastric mucosa was examined for ulcerations. RESULTS: Diazoxide accelerated the
      healing of EAGU, whereas glibenclamide aggravated EAGU. The concomitant
      administration of glibenclamide antagonized the diaoxide effect. Diazoxide
      induced acceleration of mucosal restitution was not abolished by DFMO.
      Cimetidine, omeprazole and atropine had no effect on the healing of EAGU.
      CONCLUSION: The K(ATP) channels may play an important role in the gastric mucosal
      restitution independent of polyamines. Acid inhibition cannot reverse EAGU.

PMID- 11339422
TI  - Economic evaluation of the societal costs of hepatitis B in South Korea.
AB  - BACKGROUND AND AIMS: Hepatitis B (HBV) infection remains a major public health
      problem in South Korea, and accounts for considerable morbidity and mortality. At
      present, very little is known about the cost of HBV to the South Korean health
      care system and society. The present study was therefore conducted to estimate
      the total annual cost of HBV infection in South Korea for a given year (1997).
      METHODS: The study was conducted from the South Korean societal perspective,
      taking into account the direct and indirect costs of HBV vaccination programs
      (prevention costs), and those related to the treatment of acute and chronic
      hepatitis, cirrhosis and liver cancer (disease costs). Several assumptions were
      made in arriving to actual cost estimates. RESULTS: The total societal cost of
      HBV in 1997 was 1078.3 billion Won ($US 959.7 million), 142.3 billion Won or
      13.2% being attributable to prevention costs and 225.4 billion Won or 20.9% being
      attributable to indirect costs of HBV-related diseases. The total cost (direct
      plus indirect) associated with HBV-related diseases to the South Korean society
      was 936.1 billion Won ($US 833.1 million), of which 45.3% was attributable to
      cirrhosis-related costs. In terms of disease-related direct costs alone (710.5
      billion Won or $US 632.3 million), the estimated annual spending per patient was
      1.37 million Won ($US 1219). The direct costs of the HBV disease (prevention and
      disease treatment, amounting to 782.2 billion Won or $US 696.2 million) is
      equivalent to 3.2% of the national health-care expenditure for 1997. CONCLUSIONS:
      This study confirms that HBV is a significant cost burden to the South Korean
      society, and in the absence of an effective cure reinforces the importance of
      continued disease prevention via vaccination.

PMID- 11339421
TI  - Small intestinal mucosal pattern of Myanmar children.
AB  - BACKGROUND: Little is known about the small intestinal mucosal pattern of Myanmar
      children. METHODS: Duodenal, jejunal and ileal mucosal specimens obtained from
      children within 6 h of death were examined under a dissecting microscope with the
      objective of determining villus pattern in relation to site within the small
      intestine and then correlated with age. RESULTS: Abnormalities in the small
      intestinal mucosa were detected at a very young age. In children under 1 year of
      age, the changes are more marked proximally and become less marked distally,
      perhaps reflecting exposure to the causative agent(s) in early life. Presumably
      these agents are ingested orally and inactivated progressively. The pattern in
      older children reflects more severe changes in the ileum. CONCLUSIONS: It is
      postulated that frequent intestinal infections or small bowel bacterial
      contamination could lead to damage of the intestinal mucosa.

PMID- 11339423
TI  - Generation of hepatitis C virus-specific cytotoxic T lymphocytes from healthy
      individuals with peptide-pulsed dendritic cells.
AB  - BACKGROUND AND AIMS: In hepatitis C virus (HCV) infection, cytotoxic T
      lymphocytes (CTL) are involved in liver inflammation and contribute to the
      reduction of viral load. Antibodies for HCV-CTL precursor frequencies (CTLpf) are
      relatively low in chronic hepatitis C, and this may be related to the poor CTL
      response in vivo. The aim of this study was to assess the efficacy of dendritic
      cells (DC) as antigen-presenting cells in CTL generation from low CTLpf. METHODS:
      To confirm the rationale of using DC to prime naive T cells, five HCV-uninfected
      individuals were enrolled in the study. We obtained DC by maturation from
      peripheral progenitors under stimulation with granulocyte-macrophage colony
      stimulating factor (GM-CSF), interleukin (IL)-4 and IL-1alpha. Autologous T cells
      were cultured with DC or concanavalin-A-induced blasts loaded with four HCV
      derived peptides bearing human leukocyte antigen (HLA)-A*0201 or -A24 motifs for
      28 days under IL-7 and IL-2 stimulation. The lytic activity against peptide
      pulsed targets was assessed by using a [51Cr]-releasing assay. RESULTS: The DC
      strongly expressed HLA class I, II, B7-1 and B7-2, but not phenotypic markers of
      T-, B-, natural killer (NK)-cells or monocytes. The CD8-positive, HLA-class I
      restricted and HCV peptide-specific CTL were generated with DC from HLA-A antigen
      matched subjects, whereas no CTL activity was detected with concavalin (Con-A)
      blasts. We were thus able to generate HCV specific CTL from naive precursors with
      peptide-pulsed DC. CONCLUSIONS: This DC-based system can be used to generate CTL
      of desired antigen specificity, even from a source with low CTLpf.

PMID- 11339424
TI  - Radioisotope scintigraphy in the diagnosis of hepatic hydrothorax.
AB  - BACKGROUND: Pleural effusion in cirrhotic patients (hepatic hydrothorax) may
      result from migration of ascitic fluid across defects in the diaphragm.
      Biochemical analysis of ascitic and pleural fluid provides only indirect
      information about the nature and origin of the effusion. The present study was
      performed in order to demonstrate the presence/absence of peritoneo-pleural
      communication by radioisotope imaging. METHODS: Ten patients with cirrhotic
      ascites and pleural effusion were studied with 99mTc sulfur colloid scintigraphy
      to look for movement of the radiotracer from the peritoneal to the pleural
      cavity. Serum-ascitic albumin gradient (SAAG) and serum-pleural fluid albumin
      gradient (SPAG) values were determined in eight patients to examine the nature of
      the ascitic and pleural fluids. RESULTS: Transdiaphragmatic movement of ascitic
      fluid into the pleural space was demonstrated (generally within 2 h of
      intraperitoneal injection of the radiotracer) in eight of 10 patients; six on the
      right side, one on the left and one bilaterally. Two patients in whom pleural
      fluid was transudative on SPAG values were negative for peritoneo-pleural
      communications. CONCLUSIONS: Radionuclide scintigraphy is a simple, safe and
      relatively non-invasive method to confirm passage of ascitic fluid across the
      diaphragm.

PMID- 11339425
TI  - Auditory P300 event-related potentials and number connection test for evaluation
      of subclinical hepatic encephalopathy in patients with cirrhosis of the liver: a
      follow-up study.
AB  - BACKGROUND AND AIMS: The P300 event-related potentials (P3ERP) have been recently
      advocated for detection of cognitive disturbances in early encephalopathy.
      However, no systematic follow-up study has been conducted to understand the
      clinical significance of subclinical hepatic encephalopathy (SHE) detected by
      this or other methods. The present study was therefore undertaken to examine the
      diagnostic usefulness of auditory P3ERP in the detection of SHE, to compare it
      with that of the number connection test (NCT), and to investigate the clinical
      outcome of patients with SHE in terms of progression to overt encephalopathy.
      METHODS: P300 event-related potential latencies were measured and the NCT time
      was recorded in 81 non-encephalopathic cirrhotic patients (Aged 43.8 +/- 11
      years, 23 alcoholic and 58 non-alcoholics) attending the outpatient department at
      our tertiary care hospital (All India Institute of Medical Sciences Hospital).
      Cut-off values for abnormality in the tests were developed from age-, sex- and
      education-matched controls. Patients were followed up at regular intervals for
      the development of overt encephalopathy, and the identifiable precipitating
      factors were noted. The P3ERP latencies (363 +/- 34 msec vs 349 +/- 23 msec), as
      well as NCT time (54.6 +/- 30.6 s vs 39.5 +/- 15.8 s) were significantly
      prolonged (P< 0.01) in patients with liver cirrhosis when compared with the non
      cirrhotic controls. RESULTS: The P3ERP defects were seen in 24.6% of cirrhotic
      patients, while NCT time was prolonged in 19.7% of the patients. Nearly 43% of
      the patients with SHE progressed to overt encephalopathy within a mean duration
      of 5 months, while only 3.9% of the non-SHE patients did so. Of the patients who
      developed overt encephalopathy, 64.2% had P3ERP latency prolongations while 35.7%
      had abnormal NCT. CONCLUSIONS: The results of the present study suggest that
      P3ERP and NCT are valid tools for the screening of SHE in cirrhotic patients as
      there is a greater likelihood of overt encephalopathy development in patients
      with an abnormality detected by these tests than in patients with no such
      abnormality.

PMID- 11339426
TI  - Isocitrate dehydrogenase as a marker of centrilobular hepatic necrosis in the
      experimental model of rats.
AB  - BACKGROUND AND AIMS: Serum alanine aminotransferase (ALT) and aspartate
      aminotransferase may not detect centrilobular hepatic necrosis (CLN) of a mild
      degree because these enzymes are known to be located predominantly in the
      periportal area. The aim of this study was to evaluate the usefulness of plasma
      isocitrate dehydrogenase (ICDH), which is located predominantly in the
      centrilobular zone, as a marker of CLN. METHODS: In 56 adult male rats,
      centrilobular (n = 21) and periportal hepatic necrosis (PPN; n = 21) were induced
      experimentally by the intraperitoneal injection of bromobenzene and allylalcohol,
      respectively. Seven rats were used as solvent controls in both groups. Isocitrate
      dehydrogenase and ALT activities were measured in the plasma of rats with mild to
      moderate hepatic necrosis (17 CLN and 19 PPN). Isocitrate dehydrogenase and ALT
      were compared according to the sampling time (12, 24 and 48 h) and the location
      of hepatic necrosis. Ratios of ICDH/ALT were also calculated and compared between
      CLN and PPN groups at any time points. RESULTS: Plasma ICDH activities were
      higher in rats with CLN than in those with PPN. In contrast, plasma ALT levels
      were higher in rats with PPN than in those with CLN at 12 h and were similar in
      both groups after 12 h. The ICDH/ALT ratios were much higher in rats with CLN
      compared to those with PPN (P< 0.001). The ratios were above 1.0 in 13 of 17 rats
      (77%) with CLN in contrast to none of the 19 rats with PPN. CONCLUSIONS: Our data
      suggested that the plasma ICDH/ALT ratio might be useful to differentiate between
      mild to moderate degrees of CLN from PPN, at least in the experimental model of
      rats.

PMID- 11339427
TI  - A phase one study of the hepatic arterial administration of 1,25-dihydroxyvitamin
      D3 for liver cancers.
AB  - BACKGROUND AND AIMS: It is well established that exposure to 1,25
      dihydroxyvitamin D3 (1,25(OH)2D3) inhibits the proliferation of human colorectal
      cancer and hepatoma cell lines, both in vitro and in vivo. However, clinical
      trials of the administration of 1,25(OH)2D3 and analogs for the treatment of
      malignancy have been limited by the development of hypercalcemia. 1,25
      dihydroxyvitamin D3 is principally excreted in bile following hepatic catabolism.
      This suggested the hypothesis that hepatic regional administration may allow high
      doses of 1,25(OH)2D3 to be administered for the treatment of liver cancers
      without producing hypercalcemia, caused by a clinically significant first pass
      effect. This phase one study investigates the effect of hepatic regional
      administration of 1,25(OH)2D3 on serum calcium levels, together with other
      markers of renal and liver function. METHODS: Six subjects with hepatic
      colorectal cancer metastases and one with primary hepatocellular cancer were
      given continuous hepatic arterial infusions of 1,25(OH)2D3, for periods of 1-4
      weeks. Blood samples were taken regularly and assayed for calcium levels, liver
      function tests and urea and electrolyte levels. RESULTS: Patients remained
      normocalcemic at dosages of up to 10 mcg/day. No patient experienced any side
      effects from the treatment. CONCLUSIONS: Administration of 1,25(OH)2D3 as a
      continuous hepatic arterial infusion allows a high dosage to be administered
      without inducing hypercalcemia. This route of administration may allow the
      potential of 1,25(OH)2D3 in the treatment of hepatic cancers to be realized.

PMID- 11339428
TI  - Enhanced polyadenosine diphosphate-ribosylation in cirrhotic liver and carcinoma
      tissues in patients with hepatocellular carcinoma.
AB  - AIM: The aim of this study is to assess the poly ADP-ribosylation activity in
      human hepatocellular carcinoma (HCC) and in liver cirrhosis (LC) as compared to
      the activity in normal livers (NL). METHODS: Hepatocellular carcinoma and LC
      tissues were sampled from 19 patients with HCC. Normal liver tissue was obtained
      from 19 patients with metastatic liver cancer. Poly ADP-ribosylation activity of
      these tissues was measured by using [32P]-adenylate nicotinamide adenine
      dinucleotide (NAD)-incorporation into the 116-kDa protein. Nicotinamide adenine
      dinucleotide glycohydrolase activity of these tissues was determined with thin
      layer chromatography. The immunohistochemical expression of Ki-67 was also
      assessed as a parameter of cell proliferative activity. RESULTS: The poly ADP
      ribosylation of the 116 kDa protein was significantly increased in patients with
      HCC and LC as compared with NL (P<0.0001, P<0.05, respectively) and was inhibited
      by poly (ADP-ribose) polymerase inhibitors in a dose-dependent manner. There was
      no significant difference in NAD glycohydrolase activity among the three groups.
      A significant correlation was found between the Ki-67 positive cell rate and the
      relative radioactivity of poly ADP-ribosylation in HCC patients (r=0.794,
      P<0.0001). The poly ADP-ribosylation of the 116 kDa protein of LC was
      significantly higher in patients who had recurrences of HCC after hepatic
      resection than in patients without recurrence (P<0.05). CONCLUSION: Poly ADP
      ribosylation of the 116 kDa protein in HCC patients might be enhanced with its
      proliferative activity, and poly ADP-ribosylation of the same protein in LC
      patients might be a useful parameter of carcinogenic potential for predicting HCC
      recurrence after hepatectomy in patients who have had HCC.

PMID- 11339429
TI  - Images of interest. Hepatobiliary and pancreatic: a hemodialysis patient with
      sonographic abnormalities.

PMID- 11339430
TI  - Images of interest. Gastrointestinal: gastric metaplasia in the duodenal bulb.

PMID- 11339431
TI  - A case of inability to belch.
AB  - A 22-year-old man was unable to belch. He could sense intraesophageal gas, but
      had no chest pain. An upper gastrointestinal X-ray series and endoscopic
      examination showed no abnormalities. Esophageal manometry showed normal
      relaxation of both the upper and lower esophageal sphincters with primary
      peristalsis during deglutition. However, bolus injection of air into the middle
      esophagus failed to initiate the belch reflex.

PMID- 11339432
TI  - Cavernous hemangioma of the liver with giant cyst formation: degeneration by
      apoptosis?
AB  - Cavernous hemangioma of the liver with cyst formation is a very rare condition. A
      case of cavernous hemangioma of the liver with unilocular giant cyst formation
      undergoing surgical removal is reported. Notably, the patient also had Budd
      Chiari syndrome with an obstructing lesion in the inferior vena cava. The cystic
      degeneration of the hemangioma implied a relationship with apoptosis. This is the
      first reported case of Budd-Chiari syndrome caused by advanced cystic
      degeneration of hepatic cavernous hemangioma.

PMID- 11339433
TI  - Autoimmune hepatitis with membranous glomerulonephritis.
AB  - We report on a case of autoimmune hepatitis (AIH) associated with membranous
      glomerulonephritis. A 61-year-old woman was admitted because of peripheral edema,
      proteinuria and abnormal liver function test findings. A diagnosis of AIH was
      made on the basis of an elevation of aminotransferase and serum IgG levels, the
      presence of positive antinuclear antibody and the characteristic histological
      features of chronic active hepatitis. Histological examination of a renal biopsy
      specimen disclosed membranous glomerulonephritis with granular deposits of IgG,
      IgM, C3 and C1q along the capillary walls. This condition is rare in AIH and
      should be carefully distinguished from systemic lupus erythematosus.

PMID- 11339434
TI  - The genetic basis of hyperhomocysteinemia.

PMID- 11339435
TI  - Homocysteine and vascular disease.
AB  - For more than 20 years, moderately raised concentrations of total homocysteine
      have been associated with an increased risk of atherothrombotic vascular events
      but only recently has evidence mounted to suggest that the association may be
      causal. The association is independent of other factors, it is fairly consistent
      across many studies, it is strong and dose-related, and it is biologically
      plausible. However, the evidence needs to be strengthened by a systematic review
      of all comparable studies and the demonstration, in randomised trials, that
      lowering total homocysteine is followed by a significant reduction in
      atherothrombotic vascular disease. In addition, the measurement of total
      homocysteine needs to be standardised. If these can be achieved then total
      homocysteine measurement will become another useful marker of vascular risk,
      multivitamin therapy will be another therapeutic option for people at risk of
      atherothrombotic vascular disease, and fortification of food with folic acid will
      rise high on the political and public health agenda.

PMID- 11339436
TI  - Homocysteinemia and risk for cardiovascular disease.

PMID- 11339437
TI  - Clinical spectrum and diagnosis of homocysteinemia.

PMID- 11339438
TI  - Nutritional supplementation in the management of hyperhomocyst(e)inemia: an
      update.

PMID- 11339439
TI  - Differences in risk factors, atherosclerosis and cardiovascular disease between
      ethnic groups in Canada: the study of health assessment and risk in ethnic groups
      (SHARE).
AB  - Cardiovascular disease rates vary greatly between ethnic groups in Canada. To
      establish whether this variation can be explained by differences in disease risk
      factors and subclinical atherosclerosis, we undertook a population-based study of
      three ethnic groups in Canada: South Asians, Chinese and Europeans. A total of
      985 participants were recruited from three cities (Hamilton, Toronto and
      Edmonton) by stratified random sampling. Clinical cardiovascular disease was
      defined by history or electrocardiographic findings. Carotid atherosclerosis was
      measured with B-mode ultrasonography. Conventional (smoking, hypertension,
      diabetes, raised cholesterol) and novel risk factors (markers of a prothrombotic
      state) were measured. Within each ethnic group and overall, the degree of carotid
      atherosclerosis was associated with a higher prevalence of cardiovascular
      disease. South Asians had the highest prevalence of this condition compared with
      Europeans and Chinese (11%, 5% and 2%, respectively; p=0.0004). Despite this
      finding, Europeans had more atherosclerosis (mean of the maximum intimal medial
      thickness 0.75 [0.16] mm) than South Asians (0.72 [0.15] mm) and Chinese (0.69
      [0.16] mm). South Asians had an increased prevalence of glucose intolerance,
      higher total and low-density lipoprotein cholesterol, higher triglycerides and
      lower high-density lipoprotein cholesterol, and much greater abnormalities in
      novel risk factors including higher concentrations of fibrinogen, homocysteine,
      lipoprotein(a), and plasminogen activator inhibitor-1. Although there are
      differences in conventional and novel risk factors between ethnic groups, this
      variation and the degree of atherosclerosis only partly explains the higher rates
      of cardiovascular disease among South Asians compared with Europeans and Chinese.
      The increased risk of cardiovascular events could be due to factors affecting
      plaque rupture, the interaction between prothrombotic factors and
      atherosclerosis, or as yet undiscovered risk factors.

PMID- 11339440
TI  - Homocyst(e)ine and risk of cardiovascular disease in the multiple risk factor
      intervention trial.
AB  - A nested case-control study was undertaken involving men participating in the
      Multiple Risk Factor Intervention Trial (MRFIT). Serum samples from 712 men,
      stored for upto 20 years, were analysed for homocyst(e)ine. Cases involved non
      fatal myocardial infractions, identified through the active phase of the study,
      which ended on February 28, 1982, and deaths due to coronary heart disease,
      monitored through 1990. The non-fatal myocardial infarction occurred within 7
      years of sample collection, whereas the majority of coronary heart disease deaths
      occurred more than 11 years after sample collection. Mean homocyst(e)ine
      concentrations were in the expected range and did not differ significantly
      between case patients and control subjects: myocardial infarction cases, 12.6
      micromol/L; myocardial infarction controls, 13.1 micromol/L; coronary heart
      disease death cases, 12.8 micromol/L; and coronary heart disease controls, 12.7
      micromol/L. Odds ratios versus quartile 1 for coronary heart disease deaths and
      myocardial infarctions combined were as follows: quartile 2, 1.03; quartile 3,
      0.84; and quartile 4, 0.92. Thus, in this prospective study, no association of
      homocyst(e)ine concentration with heart disease was detected. Homocyst(e)ine
      levels were weakly associated with the acute-phase (C-reactive) protein. These
      results are discussed with respect to the suggestion that homocyst(e)ine is an
      independent risk factor for heart disease.

PMID- 11339441
TI  - Homocysteine and coronary heart disease amongst Indian Asians.

PMID- 11339442
TI  - Low-Dose folic acid supplementation decreases plasma homocysteine concentrations:
      a randomised trial.
AB  - An elevated plasma total homocysteine concentration is a risk factor for
      cardiovascular disease and neural tube defects. A high daily intake of
      supplemental folic acid is known to decrease total homocysteine concentrations.
      We studied the effect of low-dose folic acid administration (250 or 500
      microg/day for 4 weeks on plasma total homocysteine concentrations and folate
      status. We also investigated whether total homocysteine concentrations and blood
      folate concentrations returned to baseline after an 8-week washout period. In
      this placebo-controlled study, 144 healthy women aged 18-40 years received 500
      microg folic acid per day, 500 microg folic acid every second day (250
      microg/day), or a placebo tablet with their habitual diet (mean dietary folate
      intake 280 microg/day). Administration of 250 and 500 microg folic acid per day
      for four weeks significantly increased folate concentrations in plasma (p<0.001)
      and red blood cells (p<0.01). Total homocysteine concentrations decreased
      significantly (p<0.001) in women (n=50) who took 250 microg folic acid daily
      [mean (+/- SEM) deviation from baseline -11.4 +/-1.98%] and in women (n=45) who
      took 500 microg folic acid daily (-21.8 +/- 1.49%). Eight weeks after the end of
      the intervention period (week 12), plasma total homocysteine concentrations in
      the folic acid-supplemented groups had not returned to baseline (week 0). In
      conclusion, doses of folic acid as low as 250 microg daily, on an average, in
      addition to usual dietary intakes of folate, significantly decreased plasma total
      homocysteine concentrations in healthy, young women. An 8-week washout period was
      not sufficient for blood folate and plasma total homocysteine concentrations to
      return to baseline concentration

PMID- 11339443
TI  - Lowering blood homocysteine with folic acid-based supplements: meta-analysis of
      randomised trials.
AB  - The objective of this study was to determine the size of reduction in
      homocysteine concentrations produced by dietary supplementation with folic acid
      and with vitamins B12 or B6. Meta-analysis of individual data on 1114 people in
      12 randomised controlled trials assessed the effects of folic acid-based
      supplements on blood homocysteine concentrations. Multivariate regression
      analysis was used to determine the effects on homocysteine concentration of
      different doses of folic acid and of the addition of vitamin B12 or B6. The
      results showed that the proportional and absolute reductions in blood
      homocysteine produced by folic acid supplements were greater at higher pre
      treatment blood homocysteine concentrations (p<0.001) and at lower pre-treatment
      blood folate concentrations (p<0.001). After standardisation to pre-treatment
      blood concentrations of homocysteine of 12 micromol/L and of folate of 12 nmol/L
      (approximate average concentrations for Western populations), dietary folic acid
      reduced blood homocysteine concentrations by 25 percent (95% confidence interval
      23%-28%; p<0.001), with similar effects in the range of 0.5-5 mg folic acid
      daily. Vitamin B12 (mean 0.5 mg daily) produced an additional 7 percent (3%-10%)
      reduction in blood homocysteine. Vitamin B6 (mean 16.5 mg daily) did not have a
      significant additional effect. In conclusion, typically in Western populations,
      daily supplementation with both 0.5-5 mg folic acid and about 0.5 mg vitamin B12
      would be expected to reduce blood homocysteine concentrations by about a quarter
      to a third (for example, from about 12 micromol/L to 8-9 micromol/L). Large scale
      randomised trials of such regimens in high risk populations are now needed to
      determine whether lowering blood homocysteine concentration reduces the risk of
      vascular disease.

PMID- 11339444
TI  - Homocysteine metabolism in health and disease.

PMID- 11339445
TI  - Long-term results after repair of total anomalous pulmonary venous connection.
AB  - BACKGROUND: Operative strategies and early results concerning repair of Total
      Anomalous Pulmonary Venous Connection (TAPVC) are relatively well known. Less
      well defined data are available to evaluate the long-term outcome. We would
      therefore like to contribute our long-term data in this presentation. PATIENTS
      AND METHODS: Between 1958 and 1992 52 consecutive patients aged two days to 42
      years (15 neonates, 16 infants, 9 children and 12 adults) with TAPVC were
      operated on. The data were collected retrospectively from the records. In 24
      patients, a current follow-up study was performed, including clinical evaluation,
      echocardiography, and a twenty-four-hour ambulatory ECG. RESULTS: Early mortality
      was 34.6% (n = 18). The postoperative follow-up period ranged from 4 months to 28
      years (mean 10.7 years). There were 4 late deaths, yielding an overall long-term
      mortality of 7.7% (4/52). Causes of death were severe hypoplasia of central
      pulmonary veins in 1, ventricular fibrillation (2) and non-cardiac in one case.
      80% of the operative survivors were available for assessment. Preoperatively, 11
      of these patients were in NYHA functional class II, six in class III and seven in
      class IV. After treatment, 22 patients were in class I and two in class II.
      Ventricular function was evaluated by echocardiography and invasive
      catheterization. Only two of 24 patients (8%) showed an abnormal IVS-motion and
      enlargement of the right ventricle. Cardiac catheterization revealed a mean PA
      pressure of 26 mmHg, the peak systolic pressure in the RV was 34 mmHg. All 24
      long-term survivors underwent assessment of cardiac rhythm by 24 h
      electrocardiogramm (ECG) monitoring. Significant arrhythmias were recorded in 11
      of 24 cases (46%), including sinus node dysfunction in 3 patients. Multiform
      ventricular ectopic beats were evaluated in 9 cases. According to the Lown
      classification, 7 patients were class I while 2 cases were considered to be class
      IV. CONCLUSIONS: A normal hemodynamic state can be achieved in most cases.
      Significant arrhythmias may exist in asymptomatic patients late after surgical
      correction of TAPVC, and therefore, long-term follow-up of these patients,
      including 24 h ECG monitoring, is recommended, even if they are asymptomatic.

PMID- 11339446
TI  - Autogenous reconstruction of infected arterial prosthetic grafts utilizing the
      superficial femoral vein.
AB  - BACKGROUND: Prosthetic infection after reconstructive vascular surgery is a most
      serious complication, associated with high mortality and amputation rates.
      Following excision of the infected graft, several methods of reconstruction are
      available. We present here our experience with autogenous reconstruction of
      infected prosthetic arterial grafts using the superficial femoral vein (SFV).
      METHODS: From November 1995 to December 1999, we used the SFV in seven patients
      (mean age 70 years) for reconstruction of an infected aortobifemoral (n = 2),
      aortoiliac (n = 1), femorofemoral bypass (n = 1), femorotibial (n = 2) and
      carotid crossover bypass (n = 1). Treatment encompassed complete prosthetic
      excision and autogenous reconstruction with the SFV alone or as a spliced graft
      with the greater saphenous vein (GSV) or basilic vein. RESULTS: There were no
      perioperative deaths or amputations. Two patients exhibited transient moderate
      swelling of the donor limb. In the follow-up, six patients are alive and well
      without any signs of recurrent infection. One patient died with an unrelated
      cause 24 months postoperatively. All donor limbs were asymptomatic for venous
      congestion in the long-term follow-up. CONCLUSION: The SFV provides a reliable
      tool for autogenous reconstruction after resection of infected prosthetic
      arterial grafts. Harvesting the SFV is well tolerated as long as the deep femoral
      and the popliteal vein are preserved.

PMID- 11339447
TI  - Shoulder-girdle strength after standard and lateral muscle-sparing thoracotomy.
AB  - BACKGROUND: There is no objective data in the literature to support the statement
      that shoulder-girdle strength can be preserved better after muscle-sparing
      thoracotomy compared with standard thoracotomy. The aim of this study is to
      determine the decrease on muscle strength with objective criteria by measuring
      the peak torque value produced by the shoulder girdle. METHOD: Peak torque values
      on abduction and adduction of entire shoulder range at the velocity of 60 and 120
      degree per second were measured with an isokinetik dynomometer which was attached
      to a computer. The measurements were performed in 20 cases, all candidates for
      thoracotomy. Patients were randomised into 2 groups; muscle sparing thoracotomy
      was undertaken in group A, and standard thoracotomy in group B. The same
      measurements were repeated 3 months after the surgery. RESULTS: The decrease in
      postoperative PT values between group A and B was statistically significant
      (p<0.003). The decrease on shoulder abduction and adduction was insignificant in
      group A (p = 0.33 and p=0.13) and statistically significant in group B (p<0.0001
      and p<0.001). CONCLUSION: These results confirm the statement that shoulder
      girdle strength is better preserved with muscle-sparing thoracotomy.

PMID- 11339448
TI  - Latrogenic tracheobronchial lesions--a report on 13 cases.
AB  - BACKGROUND: Tracheobronchial ruptures are occurrences which mainly result from
      blunt or penetrating neck or thoracic trauma, but also from long-term
      complications of intubation or tracheostomy. Acute iatrogenic tracheobronchial
      lesions are very uncommon. METHODS: From February 1995 to July 1998, we treated
      13 patients (12 female, 1 male, mean age 68 years, range 45-86) in our
      institution for iatrogenic tracheobronchial injuries after single lumen
      intubation (n = 8), double lumen intubation (n = 4), and tracheostomy (n = 1). We
      retrospectively analyzed the medical records of these patients concerning age,
      sex, symptoms, endoscopic and intraoperative findings, treatment and outcome.
      RESULTS: All patients underwent surgical treatment via right-sided thoracotomy.
      In the cases of 11 patients, repeated postoperative bronchoscopy revealed
      sufficient reconstruction of the lesions. Nevertheless, only 5 patients survived.
      The remainder died of the sequelae of trauma-related hypoxia, underlying
      (malignant) diseases, or of septic multiorgan failure after a median of 15 days
      (1 hour to 27 days). CONCLUSIONS: While technical problems of tracheobronchial
      reconstruction in our series were controllable, the long-term results were not
      satisfying. Our data suggest that the key for better outcome of these kind of
      lesions lies in an early diagnosis and immediate treatment, thus keeping the
      trauma-treatment interval with the concomitant hypoxic damage as short as
      possible.

PMID- 11339449
TI  - Aneurysmal and partially thrombosed orifice of a coronary artery fistula into the
      right atrium combined with patent foramen ovale.
AB  - We report a case of a right atrial sessile tumor combined with a patent foramen
      ovale and the characteristics of fat containing tumor in magnetic resonance
      imaging. Histologic study revealed this to be an aneurysmal and partially
      thrombosed formation of a coronary artery fistula.

PMID- 11339450
TI  - Peripheral arterial embolism originating from a thrombus in the ascending aorta.
AB  - A 45-year-old man experienced arterial thromboembolism to the right leg requiring
      surgical restoration of blood flow. Transesophageal echocardiography (TEE) was
      performed to determine the source of embolism and identified a localized
      atherosclerotic lesion in the distal ascending aorta with an adherent, highly
      mobile thrombus. The patient underwent surgery with removal of the
      atherosclerotic plaque and attached thrombus, and resection of the adjacent
      aortic wall. This case illustrates an unusual location for a complex
      atherosclerotic lesion in the ascending aorta, and points out the opportunity for
      remedial surgery once a symptomatic embolus has occurred.

PMID- 11339451
TI  - Invasive inflammatory pseudo-tumor involving the lung and the mediastinum.
AB  - Inflammatory pseudotumor is a rare clinical entity. We report here the case of a
      14-year-old boy who underwent lung resection en bloc with the lower esophagus,
      the mediastinal pleura and the diaphragm for an inflammatory pseudotumor of the
      left lower lobe. Postoperative radiotherapy was administered. The patient is well
      at 9-year follow-up. Inflammatory pseudotumor may present a particularly
      aggressive behavior. Multimodality approach, including extensive surgical
      resection, may be necessary in dealing with this disease.

PMID- 11339452
TI  - Successful management of secondary aortoesophageal fistula with graft infection.
AB  - A 60-year-old woman was transferred to our institution after massive hematemesis
      and the diagnosis of secondary aortoesophageal fistula was made. Five months
      previously, she had undergone graft replacement from the origin of the left
      subclavian artery to midthoracic aorta for chonic type B dissection. After an
      extraanatomic bypass was performed through a sternotomy, the infected thoracic
      aortic graft was resected through a left thoracotomy. She remained well without
      evidence of infection.

PMID- 11339453
TI  - Surface modification of extracorporeal circuits: is there really an impact on
      cerebral performance after cardiopulmonary bypass?
AB  - BACKGROUND: Pathophysiology of extracorporeal circulation is multifactorial, and
      the link between newly developed "biomaterials" and clinical outcome is not easy
      to illustrate. MATERIAL AND METHODS: We designed a randomized, double-blinded,
      prospective study in order to verify the impact of a new surface modification
      [SMAR(X)T] in combination with an optimized blood air interface, on the cerebral
      performance after cardiopulmonary bypass. 80 patients were randomly divided into
      two subgroups (SMAR(X)T vs. standard PVC control) and analyzed for the kinetic of
      cerebral ischemia markers neuronspecific enolase, protein S100 and
      neuropsychologically tested with the Mini-Mental-Status Test (MMST) before and
      after the operation. RESULTS: We could not show significant differences of
      protein S100 and neuron-specific enolase (NSE) levels between SMAR(X)T patients
      and the controls, but the incidence of neurological complications was
      exceptionally low. Although no statistically significant differences could be
      obtained for the MMST, the different pointloss between both groups trends toward
      a better cerebral performance in SMAR(X)T patients. CONCLUSION: The use of a
      biologically inert circuit in combination with an optimized perfusion management
      seems to be worthy of recommendation.

PMID- 11339454
TI  - Left ventricular reduction for idiopathic dilated cardiomyopathy as alternative
      to transplant--truth or dare?
AB  - BACKGROUND: Although the concept of reducing wall tension a treatment for
      advanced heart failure is convincing, clinical data from the Batista operation
      are conflicting. Despite a number of publications, it is not clear whether left
      ventricular reduction surgery truly benefits patients with idiopathic, dilated
      cardiomyopathy (DCM). Surgery may reduce wall tension, but the reason for
      dilation and contractile dysfunction remains. Thus, the potential benefit of the
      operation may be overshadowed by the natural course of the underlying disease.
      CASES: We report a series of five cases where left ventricular reduction was
      performed and physiological geometry was restored in patients with DCM by a
      modification of Dor's endoventricular patch plasty. All patients demonstrated an
      improvement in cardiac function immediately after the operation. This improvement
      was sustained in one of the patients after 18 months of follow-up. Another
      patient developed severe heart failure due to therapy-resistant ventricular
      arrhythmia (Lown IV b), and underwent successful transplantation 4 months after
      ventricular reduction surgery. Left ventricular dilation reoccurred in two
      patients 9 and 12 months after reduction surgery, and they were listed for
      transplant. One patient died after 9 weeks due to sepsis and respiratory
      dysfunction. CONCLUSIONS: Although the endoventricular patch plasty, as used in
      this study, is well tolerated by most patients with dilated cardiomyopathy, and
      results in immediate improvement of contractile function, the long-term benefits
      of this technique for DCM are uncertain. Thus, the technique is currently not an
      alternative for heart transplantation. However, the procedure may be an option in
      patients with contraindications for transplantation.

PMID- 11339455
TI  - Risk stratification for training in cardiac surgery.
AB  - BACKGROUND: There is a potential conflict of interest in providing the best
      possible outcome for patients undergoing cardiac surgery and good training for
      junior cardiac surgeons. METHODS: We analysed training with reference to volume
      of work, risk stratification and outcome for consultant and trainee procedures.
      The Parsonnet system was used for risk stratification. A retrospective audit was
      performed for a 6-year period. RESULTS: During the study period, 6037 operations
      were performed, of which 2166 were carried out by trainees. Direct consultant
      assistance in a trainee operation varied between 17% and 51% and increased
      towards the end of the study period. Of the operations performed by trainees, 88%
      were CABG. The median Parsonnet score for consultant operations was 9 compared
      with 4 for trainees. Actual mortality was below predicted for all surgeons.
      Morbidity was also lowest for trainees (10%). CONCLUSIONS: With appropriate case
      selection, trainees in cardiac surgery can achieve good results. As training
      changes in the UK, trainees should receive increased supervised exposure to a
      wider range of procedure to compensate for a lower volume of workload.

PMID- 11339456
TI  - Primary tissue failure of bioprostheses: new evidence from in vitro tests.
AB  - BACKGROUND: Primary tissue failure, which is mainly caused by calcification, is
      still the limiting factor in the long-term outcome of heart valve bioprostheses.
      Even though the precise nature of this process is not fully understood, in vitro
      tests have been developed to reproduce and predict calcification for individual
      bioprostheses. METHODS: In vitro calcification testing was performed by using an
      accelerated pulsatile valve tester which was adapted for testing stented as well
      as stentless bioprostheses with physiological fluid dynamics. A total of 84
      bioprostheses (porcine, pericardial and stentless porcine of different
      manufacturers) were cyclically loaded at a test rate of 300/min at 37 degrees C
      within a rapid calcification fluid with CaxP = 130(mg/dl)2 at pH 7.4.
      Calcification was assessed by microradiography after 12 x 10(6) cycles. In a
      previous step, holographic interferometry was performed to identify
      irregularities of valve leaflets in order to predict later calcification.
      Selected specimens of calcified bioprostheses underwent histology, transmission
      (TEM) and scanning (SEM) electron microscopy. Tissue mineralization was
      investigated by coupling SEM, electron microprobe analysis (EMPA) and X-ray
      powder diffraction (XRPD) methods. RESULTS: For all tested bioprostheses, a
      significant calcification was achieved within 4 to 6 weeks of ongoing testing,
      and the degree of calcification increased with time. A significant correlation
      between calcification and leaflet irregularities (detected by holographic
      interferometry) was found (r = 0.80, p = 0.001). Calcification varied between
      individual bioprostheses, and significant differences were detected for different
      groups (calculated as percentage of total leaflet area, mean +/- SD): porcine
      stented (37.3 +/- 12.0%), bovine stented (23.0 +/- 8.9%), porcine stentless (16.2
      +/- 7.6%). Histological and ultrastructural investigation showed intrinsic
      calcification involving both the spongiosa and fibrosa with collagen fibrils,
      interfibrillar spaces and cells as early sites of calcification. There was clear
      evidence of apatite crystallization, and observations made with in vitro
      calcification were quite similar to those occurring with in vivo implanted
      bioprostheses. CONCLUSION: In vitro tests can reproduce intrinsic calcification
      of bioprostheses even in the absence of viable biologic host factors. Moreover,
      degree and sites of calcification have become predictable. This enables the
      development and evaluation of bioprostheses with reduction of animal experiments.
      From our results obtained with a broad range of available bioprostheses, stented
      bovine and stentless porcine valves seem to be superior to conventional stented
      porcine bioprostheses with regard to leaflet calcification.

PMID- 11339457
TI  - Do changes in blood flow in the subclavian artery affect flow volume in IMA
      grafts after complete arterial revascularization with the T-graft technique?
AB  - BACKGROUND: The T-graft procedure achieves complete arterial coronary
      revascularization with only two conduits. In this technique, all the bypass
      anastomoses are supplied by the left internal mammary artery (IMA). Changes in
      flow conditions or flow redistribution in the subclavian artery may thus
      sigificantly influence coronary perfusion. The objective of this study was to
      determine whether changes in blood flow in the subclavian artery affect the flow
      in IMA grafts in patients who have undergone complete arterial revascularization
      with T-grafts. METHODS: Quantitative flow volume and flow profiles in the IMA
      graft and the proximal subclavian artery were measured with a flow-wire in 20
      patients one week postoperatively. Following baseline measurements, brachial
      artery constriction was achieved by applying a blood pressure measurement cuff to
      the patient's left upper arm. After 5 minutes, quantitative flow in the IMA and
      in the proximal subclavian artery was assessed. The cuff was then released and
      the measurements repeated. RESULTS: Flow in the subclavian artery changed
      significantly (p < 0.01) from baseline (355.4 +/- 95.2 ml/ min) to constriction
      (171.2 +/- 61.3 ml/min) and hyperemia (679.3 +/- 195.1 ml/min). Flow in the IMA
      graft remained constant irrespective of subclavian artery flow (75.4 +/- 26.2
      ml/min vs. 78.0 +/- 28.9 ml/min vs. 75.5 +/- 29.3 ml/min, respectively). The flow
      profile in the IMA was similarily unchanged. CONCLUSION: In patients in whom the
      coronary bypass blood flow is dependent on the left IMA, neither the quantitative
      flow volume nor the flow profile are altered by changes in blood flow of the
      subclavian artery.

PMID- 11339458
TI  - The influence of patient strength, aerobic capacity and body composition upon
      outcomes after coronary artery bypass grafting.
AB  - BACKGROUND: Physical activity, physical fitness and body habitus of patients may
      be important predictors of outcomes after cardiac surgery. This study sought to
      quantify physical fitness and determine whether components of fitness enhance the
      prediction of outcomes in a group of patients undergoing coronary artery bypass
      grafting. METHODS: A group of 200 patients were evaluated prior to coronary
      artery bypass surgery. A Veterans Specific Activity Questionnaire (VSAQ) measured
      aerobic capacity. A grip dynamometer assessed strength. Skin-fold thickness was
      used to calculate percent body fat and lean body mass index. Patients were
      divided into low risk (0-2.5%) and high risk (>2.5%) groups based on the STS
      National Cardiac Surgery Database prediction of operative mortality. RESULTS:
      Patients with both a high percent body fat and a low VSAQ were at higher risk for
      at least one serious complication (p<0.05) and a longer postoperative length of
      stay (p<0.05). CONCLUSION: This study suggests: 1) An index of physical fitness
      can be obtained preoperatively in cardiac surgical patients; 2) This information
      aids in the prediction of operative risk.

PMID- 11339459
TI  - Reproductive issues in adults with congenital heart disease: arrhythmias during
      pregnancy: importance, diagnosis and therapy.
AB  - Even in healthy women, increased ectopic activity is commonly seen during
      pregnancy. Congenital heart defects--whether nonoperated or operated--are, in
      general, associated with an increased risk of arrhythmias to a greater or lesser
      extent. During pregnancy, congenital heart disease patients are at increased risk
      of presenting first time with a symptomatic arrhythmia or, if previously
      diagnosed, the risk of recurrence of their arrhythmia is increased.
      Antiarrhythmic therapy should in general be restricted to the presence of
      intolerable symptoms, hemodynamic compromise or threat to the fetus and to
      patients in whom the arrhythmia may be life-threatening. The risk/benefit ratio
      must be considered for both the mother and the fetus. Considerations include the
      stage of pregnancy as well as possible effects of therapy on labor, delivery, and
      lactation. Nearly all of the presently available antiarrhythmic drugs are
      classified as Category C drugs in pregnancy. Thus, we rely on observational
      reports. Safety data are discussed for various drugs, and recommendations for the
      treatment of various arrhythmias are presented in this review.

PMID- 11339460
TI  - Long-term problems after cavopulmonary anastomosis: diagnosis and management.
AB  - After nearly three decades, the "Fontan-like" surgical approach for tricuspid
      atresia and other forms of functional univentricular heart disease have
      substantially improved life expectancy and functional status of these patients.
      However, over the years, complications such as persisting or reoccurring
      cyanosis, dysrhythmia, thromboembolism, protein-losing enteropathy and exercise
      intolerance have increasingly been reported. The management of these
      complications are related to their association with residual or recurrent
      structural lesions, which can be treated by catheter intervention or surgery, and
      to pathophysiological sequelae, directly associated to the specific
      characteristics of "Fontan-like" circulation. The recent modification might
      reduce this type of complication; however, hard data on this are not available
      yet.

PMID- 11339461
TI  - Intradural and extradural spinal metastases.
AB  - Intradural spinal metastases are uncommon. The outcome of surgical treatment of
      intra- and extramedullary intradural metastases is considered to be poor, with
      rapid clinical deterioration. The question of optimal treatment remains
      controversial. We present an overview of the clinical outcome and surgical
      treatment of 220 spinal metastases carried out in our centre from 1980 to 1999,
      with particular emphasis on 11 intradural metastases. Clinical history, signs,
      surgical approach, outcome, and radiological reports were obtained by review of
      patient charts. Secondary spinal tumours most often originated from carcinomas of
      the breast, lung, kidney, gastrointestinal tract, and prostate. In 12% of cases,
      no primary tumour could be found. Drop metastases of intracranial pathology
      appeared in 3%. Intradural metastases were seen in 11 patients and formed a very
      heterogeneous group with predominance of melanoma, lymphoma, and medulloblastoma.
      Functional recovery and survival time were worse in intradural metastases than in
      extradural metastases, and the patients were younger. Treatment of metastases is
      designed to relieve pain and preserve or restore neurological function
      palliatively. Intradural metastases are a devastating condition with usually
      fatal outcome. Selected patients who undergo aggressive surgical treatment may
      have substantially increased survival.

PMID- 11339462
TI  - Cerebral ganglioglioma with epilepsy: neuroimaging features and treatment.
AB  - Gangliogliomas are an increasingly recognized cause of epilepsy in children. In
      this study the clinical, neuroimaging, and neurophysiological data of five
      patients with cerebral ganglioglioma and epilepsy are reviewed retrospectively.
      The average age of these patients was 4.4 years at onset and the average duration
      of seizures before diagnosis was 11 months. Tumors were located in the frontal
      (3), parietal (1), and occipital (1) lobes. While one cystic and four solid
      tumors showed various densities on CT and MRI, one frontal lesion was not
      demonstrated by CT scan but clearly shown by MRI. Scalp electroencephalography
      (EEG) showed neither localized nor epileptiform abnormalities in three patients,
      while the remaining two had these abnormalities. In one patient, invasive chronic
      electrocorticography (ECoG) recordings with subdural electrodes revealed an ictal
      onset zone located in the hand motor area. In all patients, intraoperative ECoG
      failed to reveal any epileptiform activities, and tumor removal alone was
      performed. For a mean of 3.4 years after surgery, all patients are alive and
      seizure-free, with stable imaging findings. Tumor resection may be the most
      important factor for optimal seizure control and prevention of tumor recurrence
      despite the fact that EEG and ECoG findings may conflict on tumor location.

PMID- 11339463
TI  - Recurrence of benign spinal neoplasms.
AB  - The outcome of surgical treatment of benign spinal neoplasms is considered to be
      excellent, with good improvement of neurological function. The risk of recurrence
      is estimated to be very low, except with subtotal resections. This retrospective
      study was designed to establish the course of illness, clinical outcome, and
      recurrence rate of benign spinal tumours. We present an overview of the clinical
      outcome and surgical treatment of 197 benign spinal tumours carried out in our
      centre from 1980 to 1999. Clinical history, signs, surgical approach, outcome,
      and radiological reports were obtained by reviewing patient charts. The most
      frequent benign tumour was meningeoma (41%), closely followed by neurinoma (33%)
      and neurofibroma (6.1%). Of all tumours, 79.7% were completely resected.
      Recurrence happened in 10.2% on an average of 4.3 years postoperatively. Only 2
      patients suffered from neurofibromatosis. All neurinomas were completely resected
      at first operation, whereas three out of seven recurrent meningeomas and all
      ependymomas were classified as subtotally resected. Seventy per cent were treated
      by repeated surgical intervention. Benign tumours usually can be completely
      removed without adding to patients' neurological deficits. Benign tumours recur
      in 10.2% of cases, thus requiring long-term follow-up. Magnetic resonance imaging
      (MRI) studies are recommended up to 5 years postoperatively as a routine
      procedure.

PMID- 11339464
TI  - Effect of pinealectomy on immune parameters in rats with Staphylococcus aureus
      infection.
AB  - It is generally accepted that the pineal gland is a neuroendocrine organ. Several
      recent experiments have shown that the pineal gland has functional and anatomical
      connections, particularly with the immune system, and therefore the gland is now
      recognized as an important immunoneuroendocrine organ in both man and animals.
      The present study investigates the effect of pinealectomy on some immune
      parameters, including hematological alterations, and the response of the brain
      tissue against infection caused by Staphylococcus aureus. Experiments were
      performed on two different age groups of rats (neonatal and young). The results
      showed a significant reduction of the plasma zinc level in the third week
      following pinealectomy, impairment of the hematological parameters including
      lymphocyte, erythrocyte, and leucocyte, and the deficiency of the brain response
      to the infective agent, particularly in pinealectomized neonatal rats. In view of
      these data and as described previously, the pineal gland has a main regulatory
      function in immune physiology, but our study indicates that only neonatal immune
      functions are significantly affected by pinealectomy.

PMID- 11339465
TI  - Valproic acid sodium-induced spina bifida occulta in the rat.
AB  - The antiepileptic drug valproic acid is a wellknown teratogenic agent; its main
      target organ is the neuroepithelium neural tube, although skeletal malformations
      have also been described. The goal of our investigations was to determine whether
      there is a direct relationship between high doses of valproic acid and vertebral
      arch openings. On day 9 of gestation, rats were treated with either 0.3 ml
      physiologic saline or 600 mg/kg valproic acid (VA) given once in the morning and
      once in the evening (7 h between doses) for a total of 1200 mg/kg. For the
      teratological investigations, fetuses were examined at 21 days of gestation.
      Spina bifida occulta was demonstrated in double-stained fetal skeletons by
      measuring the distance between the, cartilaginous ends of each vertebral arch.
      The most important finding was the very high rate of spina bifida occulta
      observed with this application regimen. Spina bifida aperta was not observed in
      our study. A low rate of exencephaly was observed in the treated group (3%). The
      difference between the control and treated groups was statistically highly
      significant from the first thoracic to fifth sacral level. The effects of VA are
      most pronounced from thoracic 9 to the upper lumbar region. The largest gap in
      vertebral arches was found in the first and second lumbar vertebrae in the VA
      treated group. These findings suggest that the peak concentration of VA in the
      maternal plasma and high bolus administration of VA may be more important for
      spina bifida occulta than the total dose and infusion of VA.

PMID- 11339466
TI  - The effects of intravenous fentanyl and lidocaine infiltration on the hemodynamic
      response to skull pin placement.
AB  - The aim of this study was to evaluate the effects of intravenous fentanyl and
      local lidocaine infiltration on the hemodynamic response to Mayfield skull pin
      head holder (MH) placement. Forty-five patients scheduled for elective craniotomy
      were studied. They were randomly divided into three groups. Group F received
      fentanyl 2 microg/kg IV 5 min before placement of the MH, group L was
      administered plain lidocaine 3 ml 1% by infiltration at each pin site 1 minute
      before placement, and both methods were applied together in group FL. Mean blood
      pressure (MAP) and heart rate (HR) were recorded at 5 preset times. In group F
      during and after MH placement, MAP and HR were significantly higher than in the L
      and FL groups. In the L group, there was significantly higher MAP and HR during
      the placement of MH than in the FL group. In the FL group, there was no
      significant increase in MAP or HR at any time of the recordings. We conclude that
      intravenous fentanyl with local infiltration of lidocaine into the periosteum is
      effective in reducing the hemodynamic response to MH placement in patients
      undergoing craniotomy.

PMID- 11339467
TI  - Surgery of a cavernous angioma making a tunnel between the fourth ventricle and
      tubercle.
AB  - We removed a cavernous angioma, making a tunnel between the fourth ventricle and
      tubercle using the traction-dissection method. Cavernous angioma with such a
      distribution is extremely rare, and we manipulated the mass differently to
      minimize surgical damage. Intraoperative findings and technical considerations
      are made.

PMID- 11339468
TI  - Retained surgical sponges, a denied neurosurgical reality? Cautionary note.
AB  - Surgically acquired foreign bodies are well known but not widely reported. Only
      seven articles pertaining to this subject were found in the current neurosurgical
      literature. Are they a denied neurosurgical reality? In this report with a
      concededly provoking title, the authors elucidate clinical and medicolegal
      aspects of retained surgical sponges, with emphasis on spinal procedures. To
      highlight particulars, a case is presented in which a retained surgical sponge
      was encountered as the cause of progressive low back pain and tender swelling in
      the scar area after instrumented posterolateral lumbar spinal fusion combined
      with pedicle screw fixation for lumbosacral spondylolisthesis 4 years earlier.
      However, until today, no reported neurosurgical patient has suffered a serious
      complication due to a retained surgical sponge. The authors wish to remind the
      neurosurgical community to learn from unpleasant clinical and medicolegal
      experiences in other specialties before serious complications occur, and we
      suggest rigorous standardization of intraoperative habits to avoid this hazardous
      complication.

PMID- 11339469
TI  - Intradural lumbar disc herniation: report of two cases.
AB  - Intradural lumbar disc herniation (ILDH) is a rare pathology. The pathogenesis of
      ILDH is not known with certainty. Adhesions between the ventral wall of the dura
      and the posterior longitudinal ligament (PLL) could act as a preconditioning
      factor. Diagnosis of ILDH is difficult and seldom suspected preoperatively.
      Prompt surgery is necessary because the neurologic prognosis appears to be
      closely linked to preoperative duration of neurologic symptoms. Despite
      preoperatively significant neurological deficits, the prognosis following surgery
      is good. We report on two new cases of ILDH of high lumbar locations L1-2 and L2
      3 with difficult differential diagnoses, and the possible pathogenic factors are
      discussed.

PMID- 11339470
TI  - Central neurocytoma presenting with intratumoral hemorrhage.
AB  - A 22-year-old woman presented with acute onset of headache and vomiting. Computed
      tomography (CT) demonstrated hydrocephalus and a huge midline mass with
      heterogeneous density involving both lateral ventricles. A small amount of
      hematoma was detected at the bottom of the left trigone. On magnetic resonance
      imaging (MRI), the mass appeared grossly isointense on T1-weighted images and
      slightly hyperintense on T2-weighted images with a clearly demarcated low
      intensity area at its center. These CT and MRI findings were suggestive of an
      acute hemorrhagic event within the tumor. The presence of hemorrhage was
      confirmed at surgery. Sudden hemorrhages within the tumor were considered to
      cause the acute onset of symptoms. Although central neurocytoma is not commonly
      known as a tumor-producing intracranial hemorrhage or to cause abrupt clinical
      deterioration, we found five similar cases in the literature. After reviewing
      these cases, we concluded that the information on the possible hemorrhagic
      complication of central neurocytoma is important for correct diagnosis and thus
      for proper management of this tumor.

PMID- 11339471
TI  - Spinal tuberculosis (Pott's disease): its clinical presentation, surgical
      management, and outcome. A survey study on 694 patients.
AB  - Tuberculosis (TB) of the spine (Pott's disease) is both the most common and most
      dangerous form of TB infection. Delay in establishing diagnosis and management
      cause spinal cord compression and spinal deformity. This study investigated the
      data on all cases of Pott's disease reported in Turkey from 1985 to 1996. A total
      of 694 cases were included. Out of the patients evaluated, 19% were reported in
      the first half of the period (1985-1990) and 81% in the second half (1991-1996).
      Tuberculosis affecting the spine was commonly localized in the thoracic region
      and involved the vertebral body. The presenting symptoms were leg weakness (69%),
      gibbus (46%), pain (21%), and palpable mass (10%). Decompressive surgery plus
      anti-TB chemotherapy remains the best mode of therapy for Pott's disease. Follow
      up information was available in 414 of the 694 patients and there were ten deaths
      (2%), one occurring intraoperatively and the other nine postoperatively. This
      meta-analysis demonstrates that in Turkey Pott's disease remains a serious
      problem, causing paraplegia. It should be considered when patients present with
      neurological findings suggesting spinal cord compression and spinal deformity. In
      the present study, it was concluded that the neurological involvement due to
      Pott's disease is relatively benign if urgent decompression is performed at the
      onset of the disease.

PMID- 11339472
TI  - Salmonella encephalopathy with seizure and frontal intermittent rhythmic delta
      activity.
AB  - A 54-year-old woman was admitted to our clinic with frequent convulsions.
      Subsequently she developed a toxic look, rigidity, confusion and severe
      encephalopathy. Salmonella typhii was isolated from the blood cultures and she
      was diagnosed with Salmonella encephalopathy. The prominent electrophysiological
      finding was the frontal intermittent rhythmic delta activity (FIRDA) in
      electroencephalograph (EEG). After treatment EEG revealed normal activity. The
      presence of FIRDA is not a specific finding but this kind of EEG change has not
      been reported before. Diffuse encephalopathy due to endotoxins might be the
      reason. We propose that S. typhii encephalopathy was the cause of FIRDA which is
      a sign of diffuse encephalopathy.

PMID- 11339473
TI  - Clostridium sordelii corneal ulcer.

PMID- 11339474
TI  - Cellulitis and septicemia caused by Aeromonas hydrophila acquired at home.

PMID- 11339475
TI  - Lyme disease and host defense.

PMID- 11339476
TI  - The impact of nontuberculous mycobacteria on management of presumed pulmonary
      tuberculosis.
AB  - BACKGROUND: The presence of nontuberculous mycobacteria (NTM) in sputum or
      bronchial washings may cause diagnostic problems which affect clinical
      management. PATIENTS AND METHODS: In a retrospective analysis of 135 patients in
      a Dutch tuberculosis center, patients with NTM isolates were thoroughly
      investigated. Colonization or contamination by NTM was differentiated from true
      lung disease. RESULTS: 25 HIV-seronegative and two HIV-seropositive patients with
      NTM were identified. NTM were a likely cause of disease in only 14 (52%)
      patients. In 15 (55%), their presence led to preliminary diagnosis and treatment
      of tuberculosis. Unnecessary or inappropriate treatment was instituted in 17
      (63%) patients with NTM. In two patients, detection of NTM in sputum also led to
      delay in diagnosing malignant disease. CONCLUSION: In this series, NTM in sputum
      or bronchial washings poorly reflected disease and often led to diagnostic and
      therapeutic errors. Although it is common knowledge that the presence of NTM
      should be considered in smear-positive patients, this apparently is a diagnostic
      pitfall in clinical practice. Reliable DNA-based techniques and better
      communication between physicians and microbiologists may improve management of
      suspected mycobacterial infections.

PMID- 11339477
TI  - Isolation of Borrelia burgdorferi sensu lato from blood of patients with erythema
      migrans.
AB  - BACKGROUND: We assessed the isolation rate of Borrelia burgdorferi sensu lato
      from blood in European patients with typical erythema migrans and evaluated the
      course and outcome of their illness. PATIENTS AND METHODS: Adult patients
      diagnosed with erythema migrans and from whom borreliae cultured from blood were
      included in this study. RESULTS: Borreliae were isolated from the blood of
      35/2,828 (1.2%) patients, on average 7 days (range 1-47 days) after the
      appearance of erythema migrans. Only seven (20%) patients reported constitutional
      symptoms. 24/35 isolates were typed of which 20 were Borrelia afzelii and four
      were Borrelia garinii. 31 (88.6%) patients were treated with oral antibiotics
      while four (11.4%) received ceftriaxone iv. The course and outcome of the illness
      were favorable in all patients. CONCLUSION: In European patients with erythema
      migrans the yield of blood culturing was low, spirochetemia was often clinically
      silent and the course and outcome of the illness were favorable; the
      predominantly isolated strain was B. afzelii.

PMID- 11339478
TI  - Concentration of soluble CD4, CD8 and CD25 receptors in early localized and early
      disseminated Lyme borreliosis.
AB  - BACKGROUND: The aim of this study was to evaluate the concentrations of soluble
      CD4, CD8 and CD25 antigens in the serum of patients with early LocaLized, (group
      I, n = 22 patients) and early disseminated Lyme borreliosis (group II n = 23
      patients), before and after antibiotic therapy compared with controls (group III
      n = 7 healthy persons). MATERIALS AND METHODS: The diagnosis of Lyme borreliosis
      based on clinical features was confirmed by ELISA and Western blot. The assays of
      sCD4, sCD8 and sCD25 concentrations were performed using Endogen (USA) kits.
      RESULTS: In group I the sCD4 level decreased in examination 2 (p < 0.001)
      compared to examination 1. The mean concentration of sCD8 in initial examination
      1 in group II was higher than in controls (p < 0.0001); it decreased in
      examination 2 but was still higher (p < 0.01) than in controls (p < 0.006). Prior
      to treatment mean sCD25 concentration in group II was higher compared to controls
      (p < 0.0008) like in examination 2 after treatment (p < 0.02) and this persisted.
      The mean value of sCD8 in initial examination 1 before treatment in group II was
      higher than in group I (p < 0.00001). CONCLUSION: Increased initial
      concentrations of sCD8 and sCD25 indicate the activation of CD8 and CD25
      lymphocytes and their role in immunopathogenesis of Lyme disease. Elevated levels
      of sCD8 in group II before and after treatment suggest a significant involvement
      of CD8 lymphocytes, indicating the role of long-lasting cellular response in this
      stage of Lyme disease.

PMID- 11339479
TI  - Adult Enterobacter meningitis: a high incidence of coinfection with other
      pathogens and frequent association with neurosurgical procedures.
AB  - BACKGROUND: The clinical characteristics of Enterobacter infection in adult
      bacterial meningitis were defined. PATIENTS AND METHODS: The clinical
      manifestations and therapeutic outcomes of ten adult patients with Enterobacter
      infections in acute bacterial meningitis were analyzed. RESULTS: Enterobacter
      infection was found in 4.5% (10/223) of our adult patients with culture-proven
      bacterial meningitis. The ten patients comprised seven men and three women aged
      between 16-69 years (mean 47 years). Coinfections with other pathogens were found
      in 50% of the cases, the most common pathogen being Klebsiella pneumoniae. Nine
      of the ten patients had a history of neurosurgery, and seven patients contracted
      the infection nosocomially. Multiple antibiotic-resistant strains, including
      resistance to third-generation cephalosporins, were found in three patients with
      polymicrobial infections. These three patients received iv imipenem/cilastin
      therapy. The therapeutic results showed that two of the ten patients died; five
      of the eight surviving patients had neurological sequelae. CONCLUSION: The
      predominant coinfection with Enterobacteriaceae in adult Enterobacter meningitis
      may reflect the fact that most of the cases of polymicrobial Enterobacter
      infections have a potential gastrointestinal source. A postneurosurgical state
      was the most important predisposing factor for the development of Enterobacter
      infection in adult bacterial meningitis in our patients. The strains of the
      Enterobacter species in adult polymicrobial Enterobacter meningitis were commonly
      resistant to multiple antibiotics, including third-generation cephalosporins. In
      light of the high incidence of multiple antibiotic-resistant Enterobacter strains
      in adult polymicrobial Enterobacter meningitis, the choice of initial empiric
      antibiotics may include carbapenem (imipenem/cilastin or meropenem). Although the
      mortality rate was not high in this group of patients, most survivors suffered
      neurological sequelae.

PMID- 11339480
TI  - Klebsiella brain abscess in adults.
AB  - BACKGROUND: We analyzed the clinical manifestations and therapeutic outcomes of
      Klebsiella brain abscesses. PATIENTS AND METHODS: The clinical data of 15
      patients with Klebsiella brain abscesses, retrospectively collected over a 14
      year period, were studied. RESULTS: The 15 patients included 13 cases of
      Klebsiella pneumoniae infection and two cases of Klebsiella oxytoca. All but one
      case were community-acquired infections. Locations of all of these abscesses were
      supratentorial. 12 cases involved a single abscess, and three involved multiple
      abscesses. Gas formation was also found in two cases (13%). Common predisposing
      factors included metastatic spread, chronic otitis media and neurosurgical
      procedures. Among these 15 patients, 11 were treated surgically and four received
      antibiotics alone. In total, 11 patients survived and four died, with an overall
      mortality rate of 26.7%. CONCLUSION: The clinical presentations and therapeutic
      outcomes varied according to the different Klebsiella species. While debilitating
      diseases were common in K. pneumoniae infections, they were not common in K.
      oxytoca infection. And while metastatic septic abscess is a well-known,
      devastating complication of K. pneumoniae septicemia, usually seen as a brain
      abscess with a gas-forming appearance, all of these K. oxytoca infections had
      both otogenic infections and more favorable outcomes.

PMID- 11339481
TI  - Reduced leukocyte adhesiveness in response to viral versus nonviral
      infection/inflammation.
AB  - BACKGROUND: Viral infection differs from nonviral infection/inflammation by not
      producing a significant acute phase response. Since inflammation can cause
      increased adhesiveness of peripheral white blood cells (WBC), we compared these
      adhesive properties in individuals with viral infection to those with nonviral
      infection/inflammation. PATIENTS AND METHODS: The state of leukocyte
      adhesiveness/aggregation in the peripheral blood of patients with viral versus
      nonviral infection/inflammation was examined in 101 consecutive patients with
      acute febrile disease. RESULTS: A significant difference was found between the
      two groups; 13.6 +/- 7% for viral infection versus 22.8 +/- 8.5% for nonviral
      infection/inflammation (p < 0.0001). There was also a significant difference in
      the concentration of fibrinogen (361 +/- 109 mg/dl vs 554 +/- 172 mg/dl, p <
      0.0001), and in the CD11b/CD18 cell surface expression (175 +/- 66 vs 210 +/- 100
      in peripheral blood polymorphonuclear leukocytes). CONCLUSION: The results of
      this study could explain, at least in part, the differential adhesive behavior of
      the WBC in the peripheral blood in the two populations.

PMID- 11339482
TI  - Reappearance of human diphyllobothriasis in a limited area of Lake Como, Italy.
AB  - BACKGROUND: Very few sporadic cases of autochthonous diphyllobothriasis have been
      reported in Italy during the past 20 years, probably due to the drastic decrease
      or disappearance of some fish species, mainly Perca fluviatilis L., known as the
      intermediate host of the infective larval stage of this tapeworm. However,
      increasing consumption of raw or undercooked fish during the last years as
      influenced by Oriental cuisine, played an important role in a number of new
      single cases of the infection or microepidemics. PATIENTS: We describe six cases
      which were diagnosed within a period of 4 months, which all originated from the
      area of Lake Como (Lombardy region). All subjects had previously eaten raw perch
      fillets. Four individuals complained of gastrointestinal signs and symptoms,
      whereas two were asymptomatic. DISCUSSION: Parasitological diagnosis was achieved
      in four cases by recovery of typical operculated eggs in stool specimens; in two
      others by morphological features of proglottids recovered from feces. Treatment
      with niclosamide, as a single oral dose, cured the infection in all subjects.
      This is the first report of this infection in Italy in the last 10 years.

PMID- 11339483
TI  - Exchange transfusion for severe malaria.
AB  - BACKGROUND: Exchange transfusion (ET) is a controversial ancillary treatment of
      severe falciparum malaria. PATIENTS AND METHODS: We conducted a retrospective
      analysis of severe malaria treated in our institution. Nine cases of ET were
      identified between 1991 and 1998 and compared to 12 controls with similar
      parasitemia. RESULTS: Groups were similar at admission except for an increased
      age in the ET group (p < 0.02). All patients received iv quinine. Outcome was
      similar in both groups (two deaths in the ET group, three in the control group).
      However, in patients with parasitemia > 30%, the death rate was significantly
      lower in ET patients than in controls (0/4 vs 3/3, p < 0.029). CONCLUSION:
      Despite definitive data from controlled trials, we suggest that ET should be
      considered in severe malaria cases with very high parasitemia and severity
      criteria or worsening clinical condition despite adequate chemotherapy.

PMID- 11339484
TI  - Myelopathy in a previously asymptomatic HIV-1-infected patient.
AB  - A wide variety of disorders of diverse pathogenic mechanisms can trigger spinal
      cord dysfunction in HIV-1-infected patients. The most common such condition is
      HIV-1-associated myelopathy (HM) which characteristically complicates advanced
      HIV-1 disease in patients with low CD4 cell counts and previous AIDS-defining
      diagnoses. We describe an unusual presentation of HM in a previously asymptomatic
      patient with a relatively preserved CD4 cell count (458 cells/mm3) who was even
      unaware of his serological status. The patient presented with a clinically
      severe, slowly progressive myelopathy and could not walk unassisted. Significant
      neurological improvement could be obtained as rapidly as within 4 weeks after the
      institution of an antiretroviral combination of only two nucleoside analog HIV-1
      reverse transcriptase inhibitors (zidovudine and didanosine). An HIV-1 protease
      inhibitor was also prescribed at that point but could only be added to intensify
      the regimen 3 months later, when significant neurological improvement had already
      been recorded. We also review the disorders reported to derange spinal cord
      function in previously asymptomatic HIV-1-infected patients.

PMID- 11339485
TI  - The relationship between total-body mass, fat-free mass and cycle ergometry power
      components during 20 seconds of maximal exercise.
AB  - The purpose of this study was to compare the maximal exercise performance of 10
      men during friction braked cycle ergometry of 20 s duration when resistive forces
      reflected total body mass (TBM) or fat free mass (FFM). Fat mass was calculated
      from the sum of skinfold thicknesses. Increases (P < 0.05) in peak power output
      (PPO) were found between TBM and FFM (1,015+/-165 W TBM vs 1,099+/-172 W FFM).
      Decreases (P < 0.05) were observed for the time taken to reach PPO (3.8+/-1.4 s
      TBM vs 2.9+/-1 s FFM). Pedal velocity increased (P < 0.05) during the FFM
      protocol (129.4+/-8.2 rpm TBM vs 136.3+/-8 rpm FFM). Rating of perceived exertion
      (RPE) was also (P < 0.05) greater for FFM (18.4+/-1.6 TBM vs 19.8+/-0.4 FFM). No
      changes were found for Mean Power Output (MPO), fatigue index (FI) or Work Done
      (WD) between trials. These findings suggest that high intensity resistive force
      loading protocols may need to be reconsidered. Results from this study indicate
      that the active tissue component of body composition needs consideration in
      resistive force selection when ascertaining maximal cycle ergometer power
      profiles.

PMID- 11339486
TI  - Power output of legs during high intensity cycle ergometry: influence of hand
      grip.
AB  - Traditionally, leg cycle ergometry is used to assess the power output of the
      lower limbs. However, it is suspected that the upper body makes a significant,
      albeit as yet unknown, contribution to the measured power output, and as such,
      the lean mass of the whole body should be considered during ergometric
      assessment. To test this idea, indices of mechanical power output were obtained
      from 11 subjects during high intensity leg cycle ergometry tests (20 second
      duration; 75 grams per kilogram total body mass) using two protocols: one with a
      standard handle-bar grip (with grip) and one with supinated wrists (without
      grip). Peak mechanical power, mean mechanical power, fatigue index and total
      mechanical work values were calculated for each subject during each test and the
      sample mean differences associated with the two protocols were compared using
      paired Student t-tests. The with-grip protocol yielded significantly greater peak
      mechanical power output than the without-grip protocol (886+/-124 W and 815+/-151
      W, respectively), suggesting a significant upper body contribution to the maximum
      power output measured for the legs. As a first step towards quantifying the upper
      body involvement during leg cycle ergometry, surface electromyography of the
      forearm musculature was measured in a twelfth subject whilst performing each of
      the test protocols. During the with-grip ergometer tests, the intensity of
      electrical activity in the forearm musculature was similar, if not greater than,
      the intensity of electrical activity recorded for the forearm musculature during
      100% maximum voluntary hand grip-dynamometer contractions, suggesting maximum
      isometric-type forearm muscle contraction during the with-grip leg ergometry
      tests. These findings suggest that the performance of traditional-style leg cycle
      ergometry requires a muscular contribution from the whole body. As such,
      researchers should be mindful of this, both in terms of the allocation of
      ergometer loads, and in the analysis of blood-borne metabolites.

PMID- 11339487
TI  - Quadriceps concentric and eccentric exercise 2: differences in muscle strength,
      fatigue and EMG activity in eccentrically-exercised sore and non-sore muscles.
AB  - The purpose of this study was to determine whether the previously reported muscle
      weakness and increases in EMG and EMG/force ratio after eccentric exercise were
      related to ensuing soreness or simply to the exercise mode. Delayed-onset muscle
      soreness, maximal voluntary force and the surface electromyogram (EMG) of the
      quadriceps were studied in 10 healthy male subjects following 20 min of bench
      stepping with a constant leading leg. Prior to stepping and at 0, 0.25, 0.50,
      0.75, 1, 3, 24 and 48 h afterwards the subjects performed a 30 s isometric
      maximal voluntary contraction (MVC) of the extensors of each leg during which the
      isometric force and the root mean square voltage of the surface EMG (rms EMG)
      were recorded. Muscle soreness was recorded prior to and at 0, 0.75, 3, 24 and 48
      h after the stepping task by means of a force probe. No soreness was experienced
      in the concentrically exercised muscles, but in the eccentrically exercised
      muscles 5 subjects were not sore and 5 experienced soreness after 24 h,
      increasing to 48 h. There were no significant differences between sore and non
      sore muscles in muscle weakness, fatigue during 30 s, the EMG amplitudes or the
      EMG/force ratios during peak force and the 30 s MVC (p >0.05). Muscle weakness
      following eccentric exercise was related to the exercise mode and was independent
      of subsequent soreness. Both weakness and soreness may be related to muscle
      damage, but involve different mechanisms.

PMID- 11339488
TI  - Relationships between perceptions of performance expectations and mood among
      distance runners: the moderating effect of depressed mood.
AB  - Recent research has proposed that depressed mood is the most important mood
      dimension due to its de-motivating nature. Lane and Terry (2000a) proposed that
      depressed mood influences the intensity of other mood dimensions, and moderates
      the nature of anger and tension. Distance runners (N = 188) completed the 24-item
      Profile of Mood States-A (POMS-A: Terry, Lane, Lane, & Keohane, 1999) and a 7
      item Pre-race Questionnaire to assess Perceived Readiness and Course Suitability
      1 hr. before competition. On the basis of scores on the POMS-A Depression
      subscale, participants were dichotomized into a No-depression group (n = 137) or
      a Depressed mood group (n = 51). MANOVA results indicated that the Depressed mood
      group reported significantly higher scores on Anger, Confusion, Fatigue, Tension
      with lower Vigor and Perceived Readiness. In the No-depression group, Vigor
      correlated with Perceived Readiness, whereas in the Depressed mood group, Vigor
      was associated more closely with Course Suitability than Perceived Readiness.
      Anger showed a positive relationship with Perceived Readiness in the No
      depression group, and an inverse relationship with Perceived Readiness in the
      Depressed mood group. Collectively, findings lend support to the notion that mood
      and thoughts about performance are significantly associated. Further, findings
      show that depressed mood fosters a negative psychological state and moderates the
      nature of anger but not tension.

PMID- 11339489
TI  - Examination of the validity and reliability of the Accusport blood lactate
      analyser.
AB  - Clough et al. (1997) reported that 95% of lactate values obtained using an
      Accusport analyser may be up to 2.6 mM below or 2.1 mM above YSI 2300 analyser
      values over the range 0-16 mM. This variability is substantial and unsuitable for
      research purposes, The objectives of this study were to re-examine the specific
      validity and reliability of an Accusport analyser and to develop a regression
      equation to improve the accuracy of Accusport measurements. Duplicate
      measurements of lactate concentration were made on both an Accusport (Boehringer
      Mannheim) and Analox LM3 Multi Channel analyser on 17 blood samples taken from
      two subjects performing a discontinuous incremental exercise protocol. Analysis
      of duplicate measurements revealed good test-retest reliability for Accusport
      (TEM 0.35 mM; SEM 0.24 mM; ICC r = 0.995) and Analox (TEM 0.07 mM; SEM 0.09 mM;
      ICC r = 0.999). The mean values for duplicate samples recorded on both the
      Accusport and Analox between the lactate range of 1-13 mM revealed an average
      difference between the two analysers of 1.7 mM (P< 0.01, range 1.0-2.9 mM) but
      values demonstrated a high level of association (ICC r = 0.853; P< 0.05). The
      level of agreement indicated that in 95% of cases the differences would lie
      between + 0.5 to + 3.0 mM with the Accusport values always higher than Analox.
      Linear regression analysis calculated the following equation to predict Analox
      values from Accusport values: Analox = -0.749 + 0.837Accusport (R2 = 0.990). The
      results showed the portable Accusport analyser to be reliable and it demonstrated
      good association with Analox LM3 lactate analyser measures. However, a need
      exists to develop specifically generated regressions from Accusport and Analox
      LM3 analyser measures to provide more accurate results when interpreting lactate
      values from Accusport measures taken in the field.

PMID- 11339490
TI  - The validity of a repeated sprint ability test.
AB  - Many team sports require participants to repeatedly produce maximal or near
      maximal sprints of short duration (1-7s) with brief recovery periods, over an
      extended period of time (60-90 min). Therefore, an important fitness component
      for these sports is what is often termed repeated sprint ability (RSA). A variety
      of tests have been devised to assess RSA. However, while the reliability of some
      of these tests has been reported, there has been no published attempt to assess
      the validity of RSA tests. The purpose of the present paper was to assess the
      validity of a popular RSA test--the 5 x 6 s cycle test. Ten moderately-trained
      males (Mean+/-SD age: 23.6+/-3.0 yrs, mass: 71.8+/-7.4 kg, peak VO2: 46.32+/-4.16
      ml.kg(-1)min(-1)) participated in the investigation. Following familiarisation,
      subjects reported to the laboratory at the same time of day, on three occasions,
      each separated by at least 48 hours. Testing consisted of a 5 x 6 s cycle test (5
      x 6 s maximal sprints every 30 s), a graded exercise test (GXT) and a simulated
      game (3 x 15 min periods separated by five min). The simulated game consisted of
      a 1-min circuit that was repeated 15 times in each period. The circuit replicated
      typical movement patterns observed during motion analysis of field hockey games.
      Each circuit commenced with a 15-m maximum sprint through timing gates. Time to
      run 5, 10 and 15 m was recorded. Oxygen consumption was measured during both the
      GXT and the simulated game with a portable gas analysis system (Cosmed K4 b2,
      Italy). Correlation coefficients between dependent variables were calculated
      using Pearson's Product Moment (r). There was a significant correlation between
      power decrement during the 5 x 6 s cycle test and decrement in 15-m time across
      the three periods (r = 0.76, P<0.05), but not decrement in 10-m time (r = 0.54)
      or 5-m time (r = 0.42). These results suggest that the 5 x 6 s cycle test is
      valid for assessing the decrement in 15-m time, but not the decrement in 5 or 10m
      time. Thus, one measure of RSA (sprint decrement) appears to be specific to the
      test protocol, rather than a general quality. The most likely explanation is that
      the energy requirements of the 5 x 6 s cycle test more closely match those
      required to repeatedly run 15 m (mean time = 2.74 s) than to repeatedly run 10 m
      (mean time = 1.97 s) or 5 m (mean time = 1.13 s). It is therefore suggested that,
      while the 5 x 6 s cycle test is often used to assess RSA ability in a wide range
      of sports, it may need to be modified to reflect the common sprint distances
      found in specific sports.

PMID- 11339491
TI  - Feeling state responses to acute exercise of high and low intensity.
AB  - The purpose of the present study was to examine the effects of exercise intensity
      on feeling states following two acute bouts of exercise (i.e., 50% and 80% of age
      predicted maximal heart rate reserve: HRR) in highly fit and unfit females. It
      was hypothesized that highly fit females would have increased positive well-being
      and/or reduced psychological distress post-exercise (high intensity) compared to
      unfit females while both groups would experience similar feeling states following
      moderate intensity exercise. Twelve highly fit and 12 unfit females completed 3
      conditions: attention control and fitness test, and two acute bouts of exercise
      (30 minutes on a bicycle ergometer) at 50% and 80% age-predicted HRR. Pre- and
      post-exercise feeling states were measured via the Subjective Experiences
      Exercise Scale (McAuley & Courneya, 1994). Analyses indicated a time x condition
      x fitness interaction F(2,21)=6.07, p<.01 (eta2 =.37) for psychological distress.
      Follow-up univariate analyses revealed no change in the 50% or control
      conditions, however, psychological distress significantly increased for the unfit
      participants F(1,11)=4.68,p<.05 (eta2 =.29) while there was no change for the
      highly fit participants F(1,11)=2.14,p>.05 (eta2 =.16) in the 80% intensity
      condition. No fitness differences emerged with respect to positive well-being or
      fatigue. Therefore, the present study's results substantiate the need to consider
      fitness level in dose-response studies, particularly ones which examine negative
      feeling states.

PMID- 11339492
TI  - Derogation of student female athletes who consult a sport psychologist: an
      alternative perspective on the negative halo effect.
AB  - This study attempts to further research female student athletes' perceptions of
      the sport psychologist and other sport and mental health professionals. 90
      British student athletes from 17 different sports completed a two-part
      questionnaire to examine the potential derogation effect as a result of
      consulting one of three identified professionals and to explore the perceived
      definition and role of the sport psychologist. A fictitious selection report of a
      female field hockey player was presented to subjects with coach, sport
      psychologist and psychotherapist as the three professionals. It was hypothesised
      that subjects' recommendations regarding selection would differ depending on the
      consultant used. No differences were found which suggests the absence of a
      negative halo effect and that derogation would not occur within this sample
      group. Definitions and perceived role of the sport psychologist varied with the
      subjective tone of the responses from participants being mainly positive (74%).
      These results indicate that this female student athlete sample has a moderated,
      even a positive, perception of the sport psychologist. A general acceptance of
      the sport psychologist falls in line with the suggestions of Murstein and
      Fontaine (1993) concerning a reported increase in acceptance of mental health
      professionals.

PMID- 11339493
TI  - A profile of Little Athletes' injuries and the prevention methods used.
AB  - This study provides a profile of injuries sustained by Little Athletes and the
      injury prevention strategies they employed. The sample comprised 388 registered
      Little Athletes from seven Sydney New South Wales Clubs. Results from the survey
      and fieldwork suggested that at least one out of five Little Athletes had one or
      more injuries resulting from their participation in the current season. However,
      athletes aged under 11 to under 15 years were more likely to be injured than
      those in the younger age groups. The older athletes were also likely to have
      sustained more than four injuries during the season. Athletes reported low use of
      both warm up and warm down methods. Coaches, age managers and parents were
      portrayed as the key providers of information concerning injury prevention
      strategies. It was therefore noted that a valuable opportunity exists to create
      and design an innovative, age progressive educational package for Little
      Athletes, parents and coaches.

PMID- 11339494
TI  - Developing explosive power: a comparison of technique and training.
AB  - The influence of contraction type and movement type on power output of the upper
      body musculature was investigated across loads of 30-80% 1RM. Twenty seven males
      (21.9+/-3.1 years, 89.0+/-12.5 kg, 86.32+/-13.66 kg 1RM) of an athletic
      background but with no weight training experience in the previous six months
      volunteered for the study. The results were compared using multivariate analysis
      of variance with repeated measures (p< or =0.05). It was found that the
      combinations of load, movement and contraction type affected mean and peak power
      in different capacities. Mean power output for rebound motion was 11.7% greater
      than concentric only motion. The effect of the rebound was to produce greater
      peak accelerations (38.5%--mean across loads), greater initial force and peak
      forces (14.1%--mean across loads) and early termination of the concentric phase.
      Peak power output was most influenced by the ability to release the bar, the
      greater mean velocities across all loads (4.4% average velocity and 6.7% peak
      velocity) attained using such a technique appeared the dominating influence.
      Loads of 50-70% 1RM were found to maximize mean and peak power. Loading the
      neuromuscular system to maximize mean or peak power output necessitates an
      understanding of the force-velocity characteristics of the training movement and
      the requirements of the individual related to the athletic performance and their
      training status.

PMID- 11339495
TI  - Sport and recreation activities and opportunities for children with spina bifida
      and cystic fibrosis.
AB  - A survey, completed by 69 parents whose children have cystic fibrosis and 97
      parents of children with spina bifida, showed that opportunities for
      participation in sport and recreation activities were significantly greater for
      children with cystic fibrosis than for children with spina bifida. Parents from
      both groups felt that there was not enough variety available, that there was
      difficulty finding suitable activities which involved the whole family and that
      they had found barriers to their child participating in sport and recreation
      activities. The stresses of having a child with a significant disability and
      trying to balance the needs of these children with those of other non-affected
      family members was reflected by the finding that both groups of parents had
      double the rate of psychological health problems that would be expected in the
      population.

PMID- 11339496
TI  - Injury prevention and the promotion of physical activity: what is the nexus?
AB  - The promotion of physical activity is a public health priority for Australia. The
      new "National Physical Activity Guidelines for Australians" include a statement
      on additional health benefits of vigorous sporting and fitness activities.
      However, injury associated with sport and physical activity can lead to
      significant health care costs and consequent disabilities and reduced mobility
      may result in inactivity, this increasing the risk of cardiovascular disease and
      other health problems. Consideration of injury prevention principles when
      promoting physical activity is therefore crucial. There are several areas of
      research needed in this new field. These include the importance of good quality
      population monitoring and the use of other data sources to determine the
      population-wide consequences and health costs of injury sustained during sport
      and physical activity. The goal is to have evidence based, educational,
      regulatory and other preventive strategies that can be systematically evaluated
      by drawing on well organised, representative population-based injury data.

PMID- 11339497
TI  - Quadriceps concentric and eccentric exercise 1: changes in contractile and
      electrical activity following eccentric and concentric exercise.
AB  - The purpose of this study was to determine whether or not losses of strength or
      endurance following eccentric and concentric exercise are associated with reduced
      excitation. The effects of eccentric and concentric work on maximal voluntary
      isometric contraction (MVC) and surface electromyogram (EMG) of the quadriceps
      were studied in 10 healthy male subjects following bench-stepping for 20 min with
      a constant leading leg. Prior to stepping and at 0, 0.25, 0.50, 0.75, 1, 3, 24
      and 48 h afterwards the subjects performed a 30 s leg extension MVC with each leg
      during which the isometric force and the root mean square voltage of the EMG were
      recorded. In the eccentrically exercised muscles (ECC), MVC0-3 (force during the
      first 3 s of contraction) fell immediately after the bench-stepping exercise to
      88+/-2% (mean+/-SE) of the pre-exercise value and remained significantly lower
      than the concentrically exercised muscles (p<0.05). The muscle weakness in the
      ECC could not be attributed to central fatigue as surface EMG amplitude at MVC0-3
      increased during the recovery period. Muscle weakness after eccentric exercise
      appears to be due to contractile failure, which is not associated with a
      reduction in excitation as assessed by surface EMG. Muscular fatigue over 30 s
      did not change in the two muscle groups after exercise (p = 0.79), indicating
      that the ECC were weaker but not more fatiguable after exercise.

PMID- 11339499
TI  - Bidirectional communication between histamine and cytokines.
AB  - Histamine plays fundamental roles in numerous immune reactions. In addition to
      its well-characterized effects in the acute inflammatory and allergic responses,
      histamine also influences the expression and actions of several cytokines. The
      interaction between histamine and the cytokines is bidirectional, since some
      cytokines were found to modulate the production and release of histamine as well.
      Because several pharmacological agents that modulate the actions of histamine
      (e.g. antihistamines) are widely used in the treatment of various human diseases
      (allergy, peptic ulcer etc.), this complex interaction could have general medical
      relevance too, but the current situation appears to be rather controversial and
      further studies are needed to elucidate these sophisticated interactions more
      precisely.

PMID- 11339498
TI  - Granulocyte-colony stimulating factor in the prevention of postoperative
      infectious complications and sub-optimal recovery from operation in patients with
      colorectal cancer and increased preoperative risk (ASA 3 and 4). Protocol of a
      controlled clinical trial developed by consensus of an international study group.
      Part one: rationale and hypothesis.
AB  - GENERAL DESIGN: Presentation of a novel study protocol to evalue the
      effectiveness of an immune modifier (rhG-CSF, filgrastim): prevention of
      postoperative infectious complications and sub-optimal recovery from operation in
      patients with colorectal cancer and increased preoperative risk (ASA 3 and 4).
      The rationale and hypothesis are presented in this part of the protocol of the
      randomised, placebo controlled, double-blinded, single-centre study performed at
      an university hospital (n = 40 patients for each group). OBJECTIVE: Part one of
      this protocol describes the concepts of three major sections of the study:
      Definition of optimum and sub-optimal recovery after operation. Recovery, as an
      outcome, is not a simple univariate endpoint, but a complex construction of
      mechanistic variables (i. e. death, complications and health status assessed by
      the surgeon), quality of life expressed by the patient, and finally a weighted
      outcome judgement by both the patient and the surgeon (true endpoint). Its
      conventional early assessment within 14-28 days is artificial: longer periods
      (such as 6 months) are needed for the patient to state: "I am now as well as I
      was before". Identification of suitable target patients: the use of biological
      response modifiers (immune modulators) in addition to traditional prophylaxes (i.
      e. antibiotics, heparin, volume substitutes) may improve postoperative outcome in
      appropriate selected patients with reduced host defence and increased
      immunological stress response, but these have to be defined. Patients classified
      as ASA 3 and 4 (American Society for Anaesthesiologists) and with colorectal
      cancer will be studied to prove this hypothesis. Choice of biological response
      modifier: Filgrastim has been chosen as an example of a biological response
      modifier because it was effective in a new study type, clinic-modelling
      randomised trials in rodents, and has shown promise in some clinical trials for
      indications other than preoperative prophylaxis. It has also enhanced host
      defence and has been anti-inflammatory in basic research. CONCLUSION: The
      following hypothesis will be tested in patients with operations for colorectal
      cancer and increased preoperative risk (ASA 3 and 4): is the outcome as evaluated
      by the hermeneutic endpoint (quality of life expressed by the patient) and
      mechanistic endpoints (mortality rate, complication rate, relative hospital stay,
      assessed by the doctor) improved in the group receiving filgrastim prophylaxis in
      comparison with the placebo group? Quality of life will be the first primary
      endpoint in the hierarchical, statistical testing of confirmatory analysis.

PMID- 11339500
TI  - Repeated endotoxin exposure induces interstitial fibrosis associated with
      enhanced gelatinase (MMP-2 and MMP-9) activity.
AB  - BACKGROUND: Dysregulation of matrix metalloproteinases (MMPs) has been implicated
      in lung injury associated with inflammatory disorders and several lung diseases
      such as pulmonary fibrosis. OBJECTIVE: We studied a murine model of
      lipopolysaccharide (LPS)-induced chronic inflammation in order to analyse the
      relationship between MMP activity in bronchoalveolar lavage fluid and collagen
      deposition in lung tissue. BP2 mice were exposed to repeated aerosols of LPS of
      E. coli for 8 months. RESULTS: The inflammatory reaction induced by LPS increased
      throughout the time of exposure and was associated after 10 weeks with collagen
      deposition in the alveolar walls. Meantime, we observed in BAL fluid from LPS
      exposed mice an early induction of MMP-9 correlated with neutrophil recruitment.
      MMP-2 increased during the early inflammatory phase, and also during the
      development of the fibrotic phase. CONCLUSION: Repeated exposure of mice to an
      aerosol of LPS can lead to pulmonary interstitial fibrosis and MMPs seem to be
      associated with this process.

PMID- 11339501
TI  - Effects of leukotriene B4 receptor antagonist, LY293111Na, on antigen-induced
      bronchial hyperresponsiveness and leukocyte infiltration in sensitized guinea
      pigs.
AB  - OBJECTIVE AND DESIGN: LY29311 Na, 2-[2-propyl-3-[3-[2-ethyl-4-(4-fluorophenyl)-5
      hydroxyphenoxy] propoxy] -phenoxy]-benzoic acid sodium salt, is a novel
      leukotriene B4 (LTB4) receptor antagonist. Its effects on guinea pig models of
      asthma were compared with those of dexamethasone. METHODS: Effects of LY293111Na
      were tested in antigen (ovalbumin, OA)-induced bronchial hyperresponsiveness
      (BHR) and leukocyte accumulation in actively sensitized guinea pigs. Its effects
      on antigen-induced acute bronchoconstriction in passively sensitized guinea pigs
      were also studied. RESULTS: LY293111 Na (10 to 30 mg/kg p.o., 1 h before and 6 h
      after OA challenge) inhibited BHR to acetylcholine. LY293111 Na (3 mg/kg p. o.)
      significantly inhibited accumulation of neutrophils in bronchoalveolar lavage
      (BAL) fluid 24 h after antigen challenge but it did not inhibit accumulation of
      eosinophils and macrophages at any doses used. In contrast, dexamethasone (30
      mg/kg p.o., 4 h before OA challenge) not only inhibited BHR but also reduced the
      infiltration of all three types of leukocytes. A significant increase of LTB4
      levels in BAL fluid was noted at 3 and 15 min after the antigen challenge.
      LY293111Na did not inhibit antigen-induced acute bronchoconstriction in passively
      sensitized guinea pigs. CONCLUSION: These results indicate that LTB4 may
      participate in antigen-induced BHR but not in eosinophil infiltration and acute
      bronchoconstriction in guinea pigs.

PMID- 11339502
TI  - Fibronectin regulates the activation of THP-1 cells by TGF-beta1.
AB  - OBJECTIVE AND DESIGN: To determine how fibronectin regulates the immunomodulatory
      effects of transforming growth factor (TGF)-beta on THP-1 cells. MATERIAL OR
      SUBJECTS: THP-1 monocytic cell line. TREATMENT: THP-1 cells were primed for 48 h
      in the presence or absence of 250 pM TGF-beta1. METHODS: Assays or assessments
      carried out, together with statistical test applied. RESULTS: We found that
      adherence to fibronectin dramatically modulates the effects of TGF-beta1 on the
      human monocytic cell line THP-1. TGF-beta did not significantly affect
      constitutive interleukin (IL)-8 secretion or IL-1beta-induced IL-8 secretion from
      suspended cells. In contrast, TGF-beta stimulated IL-8 secretion as well as
      augmented IL-1beta-induced IL-8 secretion from adherent cells. The differential
      effects of TGF-beta1 on IL-8 secretion from suspended and adherent cells could
      not be explained by differences in IL-1 receptor antagonist production. The
      effects of fibronectin on TGF-beta1 induced IL-8 secretion from THP-1 cells were
      mimicked by adhesion to immobilized anti-a4beta1 integrin antibody and to a
      fibronectin fragment containing the CS-1 domain. CONCLUSIONS: These results
      indicate that alpha4beta1-mediated adhesion to fibronectin may play a key role
      during inflammation by profoundly influencing the effects of TGF-beta1 on
      monocytes.

PMID- 11339503
TI  - Bradykinin receptor antagonists type 2 attenuate the inflammatory changes in
      peptidoglycan-induced acute arthritis in the Lewis rat.
AB  - OBJECTIVE AND DESIGN: We studied the ability of bradykinin (BK) receptor
      antagonists type 1 and 2 (B1-RA, B2-RA) to prevent acute inflammation. MATERIAL:
      A peptidoglycan-polysaccharide (PG-APS)-induced model of arthritis in the Lewis
      rat was analyzed. TREATMENT: Four groups of animals were studied for 5 days.
      Treatment was administered subcutaneously (s.c.) 1 mg/kg every 12 h. Group I
      received PG-APS and was treated with the B2-RA, CP-0597 (DArg-Arg-Pro-Hyp-Gly-Thi
      Ser-DTic-NChg-Arg). Group II received PG-APS and was treated with a combined B1
      and B2-RA, B9430 (DArg-Arg-Pro-Hyp-Gly-Igl-Ser-Dlgl-Oic-Arg). Group III received
      PG-APS and albumin control. Group IV received albumin control. METHODS: Joint
      diameter, liver weight, hematocrit, white blood count and plasma concentrations
      of prekallikrein, high molecular weight kininogen, HK and IL-beta were measured.
      Groups were compared by ANOVA. RESULTS: Acute arthritis and hepatomegaly were
      attenuated in the B2-RA-treated animals (p<0.05). Weight loss was more pronounced
      in the B1/B2-RA-treated animals. Anemia induced by PG-APS was prevented by B2-RA
      and B1/B2-RA treatment (p<0.001). A marked decrease in plasma HK to 64% of normal
      was found in the disease-untreated animals, which was completely normalized by B2
      RA treatment and partially attenuated by the B1/B2-RA (78%). The decrease in
      plasma prekallikrein levels was prevented by combined B1/B2-RA treatment
      (p<0.05). Finally, elevated plasma IL-1beta levels were lowered by B1/B2-RA
      treatment and were below detection limits with the B2-RA treatment. CONCLUSIONS:
      These results indicate that the systemic inflammation is due in part to BK
      generation which can be blocked by B2-RA, while inhibiting the B1 receptor
      prevents an anti-inflammatory response.

PMID- 11339504
TI  - Evaluation of the expression of NADPH oxidase components during maturation of HL
      60 clone 15 cells to eosinophilic lineage.
AB  - OBJECTIVE: Superoxide-generating NADPH oxidase consists of the membrane-bound
      cytochrome b558 (gp91phox and p22Phox) and the cytosolic components (p67phox,
      p47phox, p40phox and rac). In this study, we evaluated the superoxide-generating
      activity and the expression of NADPH oxidase components during eosinophilic
      maturation using HL-60 clone 15 cell line. MATERIALS AND METHODS: HL-60 clone 15
      cells were matured to eosinophils by incubation with 0.5 mM butyrate for 7 days,
      and NADPH oxidase components were detected by Northern blot, Western blot
      analyses and immunocytochemical staining. Moreover, superoxide-generating
      activity was examined by nitro blue tetrazolium (NBT) assay. RESULTS: Northern
      blot and Western blot analyses revealed that mRNAs and proteins for gp91phox,
      p67phox and p47phox were expressed after eosinophilic myelocyte stages, whereas
      mRNAs and proteins for p40phox and rac-2 were expressed from the promyelocyte
      stage. Interestingly, p22phox mRNA was expressed from the promyelocyte stage, but
      its protein was expressed after eosinophilic myelocyte stages. Consistent with
      the results of Western blotting, immunocytochemical staining of butyrate-induced
      HL-60 clone 15 cells indicated that gp91phox, p22phox, p67phox and p47phox were
      detected after eosinophilic myelocyte stages (eosinophilic myelocytes,
      eosinophilic metamyelocytes, eosinophilic band cells and eosinophilic-segmented
      cells), whereas p40phox and rac-2 were expressed from the promyelocyte stage.
      Moreover, almost the same results as those with butyrate-treated HL-60 clone 15
      cells were obtained using human bone marrow cells by immunocytochemical staining.
      Furthermore, nitro blue tetrazolium (NBT) assay indicated that superoxide could
      be produced after eosinophilic myelocyte stages but not produced before the
      promyelocyte stage. CONCLUSIONS: Together these observations indicate that all
      the components for NADPH oxidase are expressed, and the superoxide-producing
      activity is obtained after myelocyte stages during eosinophilic maturation.

PMID- 11339505
TI  - Stem cell factor and igE-stimulated murine mast cells produce chemokines (CCL2,
      CCL17, CCL22) and express chemokine receptors.
AB  - OBJECTIVE AND DESIGN: In the present study we investigated the effect of SCF
      and/or IgE on histamine, TNF-alpha and chemokines released from bone marrow
      derived mast cells (BMMC) as well as chemokine receptor expression. MATERIAL AND
      METHODS: BMMC were derived from femoral bone marrow of CBA/J mice. The purity of
      BMMC was >98% after 3 weeks. BMMC (2.5 x 10(6) cells/well) were incubated in the
      presence or absence of either SCF, IgE plus DNP or a combination of SCF and IgE
      for 6 and 18 h. Cell-free supernatants were recovered to measure CC chemokines,
      TNF-alpha and histamine release utilizing ELISA assays. CC chemokine family
      receptors were detected by RT-PCR analysis, and confirmed using functional
      chemotactic assays. RESULTS: Histamine levels were comparable between SCF and IgE
      stimulated cells, whereas TNF-alpha production was significantly greater after
      IgE compared to SCF stimulation. SCF and/or IgE-stimulated BMMC released CC
      chemokines, CCL22 (MDC), CCL17 (TARC) and CCL2 (MCP-1). Increased mRNA expression
      of CCR1, CCR2, CCR3, and CCR5 was detected in SCF and IgE-stimulated BMMCs.
      Functional chemotactic assays confirmed the expression data. CONCLUSION: SCF and
      IgE can up-regulate the expression of chemokines and chemokine receptors on mast
      cells. Thus, SCF may play a significant role in their activation and inflammation
      during allergic responses.

PMID- 11339506
TI  - Effects of tetracyclines on the production of matrix metalloproteinases and
      plasminogen activators as well as of their natural inhibitors, tissue inhibitor
      of metalloproteinases-1 and plasminogen activator inhibitor-1.
AB  - OBJECTIVE: Evaluation of tetracycline effects on the expression of MMP-1, MMP-3,
      tissue inhibitor(s) of metalloproteinase-1 (TIMP-1), plasminogen activators (PA),
      and PA inhibitor-1, which are all involved in the ultimate regulation of MMP
      activity could provide new insight into how tetracyclines achieve their cartilage
      preserving effects. MATERIALS AND METHODS: We used bovine articular chondrocytes
      cultured in alginate gel beads for our studies which were initially treated with
      10 microM tetracyclines in the presence of IL-1. Only significant effects were
      studied at additional concentrations. Expression of mRNA was analyzed by RT-PCR
      ELISA. The activity of enzymes and TIMP was measured by functional assays;
      whereas, the level of PAI-1 was determined by ELISA. RESULTS: Treating
      chondrocytes with IL-1 induced the expression of MMPs and downregulated TIMP-1
      but stimulated both the expression of PAs and PAI-1. When tested at 10 microM
      only minocycline reduced collagenase activity and expression of MMP-1. Further
      pharmacokinetic analysis revealed IC50 values of 26 microM and 16 microM for the
      inhibition of collagenase activity and mRNA expression, respectively. Production
      of MMP-3 was only decreased by tetracycline (IC50 = 45.4 microM). No effects of
      tetracyclines could be observed on proteoglycan degradation, TIMP activity and
      the production of PAs, PAI-1, and TIMP-1. CONCLUSIONS: We conclude that the
      inhibition of MMPs by tetracyclines occurs mainly via down-regulation of the
      respective gene expression.

PMID- 11339507
TI  - In vitro melatonin treatment enhances cell-mediated immune function in male
      prairie voles (Microtus ochrogaster).
AB  - The present study was designed (1) to determine the extent to which male prairie
      voles (Microtus ochrogaster) alter immune status in response to short-day
      lengths, (2) to evaluate the role of melatonin in coordinating these alterations
      in immune function, and (3) to assess the association between alterations in
      immune function and reproductive responsiveness to photoperiod. Male voles were
      housed in either long- or short-day lengths for 10 wk; voles in short days were
      subdivided into reproductive "responders" (R) or "non-responders" (NR) based on
      testicular mass at autopsy. After 10 wk of exposure to photoperiodic conditions,
      cell-mediated immune function was evaluated using an in vitro splenocyte
      proliferation assay. The direct effects of melatonin on immune cells were
      evaluated by adding melatonin to one-half of the cultures in each experimental
      condition. Melatonin treatment led to enhanced splenocyte proliferation for all
      experimental groups. Neither photoperiodic condition nor reproductive status was
      associated with alterations in immune function or the degree of immuno-enhancing
      effects of melatonin. Taken together, the results of the present study suggest
      that melatonin is capable of enhancing immune function in male voles potentially
      by acting directly on immune cells.

PMID- 11339508
TI  - Melatonin stimulates glutathione peroxidase activity in human chorion.
AB  - In preeclampsia, placental production of lipid peroxides is abnormally increased,
      while placental glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD)
      activities are decreased. Administration of melatonin, a powerful scavenger of
      oxygen free radicals, also may protect the placenta from free radical-induced
      damage by increasing the activity of antioxidant enzymes. To test this hypothesis
      we administered melatonin to pregnant women before they underwent voluntary
      interruption of pregnancy between 7 and 9 wk of gestation. Melatonin (6 mg) was
      administered orally at 12:00 hr, and samples of chorion and maternal blood were
      obtained at the time of the procedure, 1, 2 or 3 hr later. We measured the
      melatonin concentration in maternal serum and activities of GSH-Px and SOD and
      levels of melatonin in chorionic homogenates. Melatonin administration was
      reflected by markedly increased melatonin concentrations in maternal serum and in
      chorion, with peak levels achieved 1 hr after melatonin administration (serum,
      46.87 +/- 10.87 nM/L; chorionic homogenate, 4.36 +/- 1.56 pmol/mg protein).
      Between 1 and 3 hr after melatonin administration, GSH-Px activity in chorionic
      homogenates increased significantly (P < 0.001), with peak levels occurring at 3
      hr (51.68 +/- 3.22 mU/mg protein per min, 137.3% of GSH-Px activity in untreated
      control subjects). No significant changes in chorionic SOD activity occurred
      during the 3-hr post-administration period. These results indicate that exogenous
      melatonin increases GSH-Px activity in the chorion and thereby may protect
      indirectly against free radical injury. Melatonin could be useful in treating
      preeclampsia and possibly other clinical states involving excessive free radical
      production, such as intrauterine fetal growth retardation and fetal hypoxia.

PMID- 11339509
TI  - Salivary melatonin response to acute pain stimuli.
AB  - Evidence for a relationship between melatonin, nociception, and analgesia in
      humans is based on data that are only linked by association and simultaneous
      occurrence. Studies have reported inverse correlation of the circadian melatonin
      rhythm with nociception latency and enhancement of opioid analgesia by
      simultaneous administration of melatonin in animals. This study examines the
      response of salivary melatonin to acute pain stimuli in 18 healthy subjects
      ranging in age from 19 to 50 years. A biphasic melatonin response following an
      acute pain stimulus of 36 V was observed, F(8, 8) = 17.839, P < 0.001. Within 5
      min of the stimulus, melatonin decreased and reached a plateau of 36 pg/mL below
      baseline by 20 min. This decrease was followed by an increase of 5 pg/mL.
      Melatonin levels subsequently decreased until they had reached levels similar to
      those anticipated for the time of day and did not vary thereafter. The magnitude
      of the melatonin response was not related to age or gender. There was no
      association between voltage and magnitude of the melatonin responses observed at
      15 min (r =0.185, P=0.51) or at 30 min (r = 0.468, P = 0.09). This study provides
      the first evidence of melatonin utilization and subsequent pineal gland synthesis
      following acute pain episodes in humans.

PMID- 11339510
TI  - Increased pineal Fdopa uptake is related to severity of Parkinson's disease--a
      PET study.
AB  - We investigated regional L-3,4-dihydroxy-6-[18F]fluoro-phenyl-alanine (Fdopa)
      uptake within the pineal gland using co-registration of Fdopa PET and MRI images.
      Data from 12 early Parkinson's disease (PD) and 9 advanced PD patients were
      compared with those from 13 age-matched healthy controls. We found a significant
      increase of Fdopa influx constants (Ki) and relative Fdopa tracer activity in the
      pineal gland of PD patients. Additionally, significant correlations were found
      between Ki and the Hoehn and Yahr (H&Y) scores, and between the relative Fdopa
      activity and the parameters disease duration, H&Y disease score and Unified
      Parkinson's Disease Rating Scale (UPDRS). Our studies in patients with PD
      indicate a participation of extrastriatal dopaminergic structures within the
      scope of pathophysiological processes in PD. The result may be explained as a
      compensatory upregulation of monoaminergic transmitter systems outside the basal
      ganglia. Increased Fdopa uptake in the pineal gland may reflect pineal
      dysfunction in PD patients.

PMID- 11339511
TI  - Melatonin inhibits PHA-stimulated chicken lymphocyte proliferation in vitro.
AB  - Many studies have shown that melatonin plays a fundamental role in
      neuroimmunomodulation. There are known differences between mammals and birds in
      immunomodulatory function of melatonin exerted in vivo. In present study the
      effect of exogenous melatonin on chicken lymphoid cell proliferation in vitro was
      examined. Melatonin alone (10(-10)M-10(-5)M) did not exert any effect on the
      proliferation of the chicken thymocytes, splenocytes and lymphocytes from the
      bursa of Fabricius. On the other hand, melatonin addition strongly inhibited the
      proliferation of PHA-activated thymocytes and splenocytes from young chickens.
      The effect of melatonin was hormone- and mitogen-(PHA) dose-dependent; the most
      pronounced effect was obtained at low PHA and melatonin concentrations i.e., 1.6
      3.125 microg/100 microl of PHA and 10(-10) M-10(-7) M melatonin, respectively.
      Prior immunization of chickens with sheep red blood cells (SRBC) inhibited the
      proliferative response of splenocytes to the same dose of PHA and, consequently,
      the effect of melatonin addition was not observed. The results reported
      demonstrate a direct inhibitory effect of melatonin on in vitro activated chicken
      lymphocytes.

PMID- 11339512
TI  - Endogenous rhythms of melatonin, total antioxidant status and superoxide
      dismutase activity in several tissues of chick and their inhibition by light.
AB  - Melatonin was recently shown to be a component of the antioxidative defense
      system of organisms due to its free radical scavenging ability and to its
      capacity to stimulate several antioxidant enzymes. In this report, we studied the
      endogenous rhythm of the antioxidant enzyme superoxide dismutase (SOD) in three
      different tissues (cerebral cortex, liver and lung) of chick (Gallus domesticus)
      (three weeks, at age and sacrificed every 2 hr). During the study the chicks were
      under a light:dark cycle of 12:12. Total antioxidant status of the plasma was
      correlated with physiological blood melatonin concentrations. Superoxide
      dismutase activity exhibited a marked 24 hr rhythm in cerebral cortex, lung and
      liver, with peak activity coincident with the melatonin and total antioxidant
      status peaks. The exposure of chicks to constant light for 7 days eliminated the
      melatonin rhythm as well as the peaks in superoxide dismutase activity and the
      total antioxidant status. These findings suggest that the melatonin rhythm may be
      related to the nighttime increase in the superoxide dismutase activity and to
      total antioxidant capacity of the blood.

PMID- 11339513
TI  - Intracellular Ca2+ signaling pathway is involved in light-induced phase advance,
      but may not be in phase delay, of the circadian melatonin rhythm in chick pineal
      cell.
AB  - Chick pineal cells have photoreceptive, circadian clock and melatonin synthetic
      capacities, and express circadian oscillation of melatonin release in vitro.
      Light pulses cause phase-dependent phase shift of the melatonin rhythm. The
      purpose of this study was to address the questions whether intracellular calcium
      is involved in both light-induced phase advance and delay. Thapsigargin and
      cyclopiazonic acid, which deplete the intracellular calcium stores, blocked the
      light-induced phase advance in a dose-dependent manner. The pulses of ryanodine
      receptor antagonist (dantrolene sodium or ruthenium red) also blocked the light
      induced phase advance. Most agents did not cause a significant phase shift by
      themselves. On the other hand, all the agents used, failed to block the light
      induced phase delay, even if the magnitude of phase delay was decreased using low
      intensity light. An antagonist of nitric oxide synthase blocked neither light
      induced phase advance nor phase delay. These results indicate the following
      possibilities: (1) the mechanism of light-induced phase advance and delay may be
      different in chick pineal cells, or (2) if intracellular calcium is involved in
      both light-induced phase advance and delay, the sensitivity to light and/or
      agents used in this study may differ according to Zeitgeber time.

PMID- 11339514
TI  - Gene expression of the key enzymes of melatonin synthesis in extrapineal tissues
      of the rat.
AB  - Besides the pineal gland, melatonin is reported to be produced in a number of
      extrapineal sites, where it could act as an intracellular mediator or paracrine
      signal in addition to its endocrine effects. In view of the suggested
      immunoregulatory role of melatonin, we compared lymphoid organs and several other
      tissues of the rat for their potential to synthesize melatonin. Using the reverse
      transcription-polymerase chain reaction (RT-PCR) method, we determined the tissue
      specific expression of mRNAs encoding two key enzymes of the melatonin
      biosynthesis: serotonin-N-acetyltransferase (NAT) and hydroxyindole-O
      methyltransferase (HIOMT). The minimal number of PCR cycles required to obtain a
      positive signal served as a measure for the abundance of a given mRNA. NAT and
      HIOMT mRNAs were detected in all tested tissues at high numbers of PCR cycles (40
      and 45, respectively). At 35 cycles, only gut, testis, spinal cord, raphe nuclei,
      stomach fundus and striatum yielded positive signals for both enzymes. In
      conclusion, the presence of NAT and HIOMT mRNAs in a wide range of tissues
      corroborates and extends the notion of extrapineal melatonin synthesis.
      Comparatively low levels of the HIOMT messages in lymphoid organs, however,
      indicate a limited significance of melatonin synthesis within the immune system.

PMID- 11339515
TI  - Comparison of intramuscular and oral meloxicam in rheumatoid arthritis patients.
AB  - OBJECTIVE: This double-blind, double-dummy, two-way comparative trial evaluated
      the overall efficacy and tolerability of intramuscular (im) vs oral meloxicam.
      SUBJECTS: 346 patients with rheumatoid arthritis (RA). TREATMENT AND METHODS: 173
      patients in each group were randomised to receive either im meloxicam (15 mg)
      plus a placebo tablet, or oral meloxicam (15 mg) plus a placebo injection for 7
      days. RESULTS: Significant (p < 0.001) improvements in overall pain and disease
      activity were observed by patients treated with im and oral meloxicam, with no
      significant difference between treatments. The im formulation was better than the
      oral tablet in terms of rapidity of action (p=0.012), global efficacy (p=0.030)
      and duration of morning stiffness (p=0.026). Local tolerability of im meloxicam
      was very good and comparable with placebo injections. CONCLUSION: Oral and im
      meloxicam (15 mg) were both effective and well-tolerated for acute exacerbations
      of RA. The im formulation had some advantages, such as a faster onset of action.

PMID- 11339516
TI  - Oral meloxicam is effective in acute sciatica: two randomised, double-blind
      trials versus placebo or diclofenac.
AB  - OBJECTIVE: Two randomised, double-blind, double-dummy trials evaluated the
      efficacy and tolerability of meloxicam compared with placebo or diclofenac in
      patients with acute sciatica. SUBJECTS: 1021 patients with acute sciatica.
      TREATMENT AND METHODS: In the first study, 532 patients received meloxicam 7.5
      mg, meloxicam 15 mg, or placebo for 7 days. The second study randomised 489
      patients to meloxicam 7.5 mg, meloxicam 15 mg, or diclofenac 150 mg for 14 days.
      RESULTS: Meloxicam 7.5 mg and 15 mg significantly improved overall pain between
      baseline and day 7 (p < 0.05) compared with placebo. Furthermore, both meloxicam
      doses showed similar improvements on all primary and secondary efficacy endpoints
      compared with diclofenac 150 mg. No significant differences in tolerability were
      observed between any of the treatment groups in either study. CONCLUSIONS:
      Meloxicam (7.5 mg or 15 mg) was well tolerated and was more effective than
      placebo, and as effective as diclofenac, in acute sciatica.

PMID- 11339517
TI  - Meloxicam in acute episodes of soft-tissue rheumatism of the shoulder.
AB  - OBJECTIVE: This double-blind, randomised trial compared the efficacy and safety
      of meloxicam vs piroxicam in patients with soft-tissue rheumatism of the
      shoulder. SUBJECTS: 599 outpatients at 88 centres in 9 countries. TREATMENT AND
      METHODS: Oral meloxicam 7.5 mg, meloxicam 15 mg or piroxicam 20 mg, once-daily
      for 14 days. The primary efficacy endpoint was the assessment of pain on day 7
      relative to day 1. RESULTS: Once-daily treatment with meloxicam 7.5 or 15 mg was
      comparable to piroxicam. A significantly higher proportion of meloxicam-treated
      patients had pain relief within day 1 or day 3. The incidence and intensity of
      adverse events was comparable between the treatment groups, although fewer
      patients in the meloxicam groups withdrew due to adverse events. There were no
      apparent differences between the two meloxicam doses. CONCLUSIONS: Treatment with
      meloxicam was at least as effective as treatment with piroxicam, with a
      favourable global tolerability for both doses of meloxicam.

PMID- 11339518
TI  - Meloxicam: new formulations and their use in rheumatology.

PMID- 11339519
TI  - A comparison of the efficacy and tolerability of meloxicam and diclofenac in the
      treatment of patients with osteoarthritis of the lumbar spine.
AB  - OBJECTIVE: The aim of this study was to evaluate the efficacy and tolerability of
      meloxicam compared with diclofenac in patients with osteoarthritis of the lumbar
      spine. SUBJECTS: 229 patients with radiologically confirmed osteoarthritis of the
      lumbar spine. TREATMENT AND METHODS: Once-daily meloxicam 7.5 mg tablet or
      diclofenac 100 mg slow release tablet. Efficacy and tolerability parameters were
      assessed at baseline and after 3, 7 and 14 days of treatment. RESULTS: The two
      drugs had equal short-term efficacy, with pain on motion of lumbar spine
      significantly (p<0.05) decreased at Day 3. Secondary efficacy variables were also
      significantly improved at Days 3, 7 and 14. There were no statistically
      significant differences between the two drugs, although the global tolerability
      of meloxicam was significantly better than for diclofenac, as assessed by the
      investigators (p = 0.0072) and the patients (p = 0.049). CONCLUSIONS: Meloxicam
      and diclofenac were equivalent in relieving the acute pain associated with
      osteoarthritis of the lumbar spine. However, meloxicam was much better tolerated.

PMID- 11339520
TI  - Meloxicam oral suspension: a treatment alternative to solid meloxicam
      formulations.
AB  - This paper reviews recent studies that have aimed to establish the relative
      bioavailability of a new oral formulation of meloxicam, and to evaluate its
      safety and efficacy in a clinical setting. For the bioavailability study, 16
      healthy volunteers were randomised to receive either an oral or a solid
      formulation of meloxicam 15 mg. The performance of the oral suspension was tested
      in 286 patients with osteoarthritis who were randomised to receive either
      formulation at 7.5 mg daily. It was found that the new oral suspension was
      bioequivalent to the capsules formulation, and was more rapidly absorbed after a
      single dose. No clinical differences were observed in both efficacy and
      tolerability parameters with either type of formulation in patients with
      osteoarthritis. The oral suspension was well accepted by the patients. Hence, the
      oral suspension provides a useful alternative to solid formulations in the
      treatment of inflammatory joint diseases and painful musculoskeletal disorders.

PMID- 11339521
TI  - Meloxicam: a review of its pharmacokinetics, efficacy and tolerability following
      intramuscular administration.
AB  - This paper reviews published studies on the intramuscular use of meloxicam in
      acute rheumatic conditions. Data were obtained from 68 healthy volunteers and
      >800 patients with conditions such as arthritis, sciatica and lumbago who were
      treated with intramuscular injections of meloxicam compared with oral
      formulations. Intramuscular meloxicam appears to have a more rapid onset of
      action than oral meloxicam in acute inflammatory rheumatism. Local tolerance of
      im meloxicam was consistently good in both volunteers and patients, with respect
      to creatine phosphokinase levels and local reactions. Meloxicam im was also
      superior to other drugs such as piroxicam with respect to local tolerance. The
      incidence of adverse events, including gastrointestinal events, was low.
      Therefore, im meloxicam is an alternative to achieve rapid relief of acute pain
      in patients with acute inflammatory rheumatism. However, the recurrent use of im
      meloxicam is not recommended and patients should be switched to the oral
      formulation for chronic use.

PMID- 11339522
TI  - Angular response of a HPGe detector to gamma-rays in in situ measurements.
AB  - The angular response of a HPGe detector used in in situ measurements was
      determined empirically as a function of gamma-ray energy at two source-detector
      geometries--the standard 1 m and the non-standard 0.1 m heights above ground.
      Values calculated by a Monte Carlo code were found to agree well with the
      experimental values. The code is thus labor-saving, because it can spare many
      measurements required for the empirical determination of the angular response in
      an unknown experimental configuration.

PMID- 11339523
TI  - Monte Carlo determination of full energy peak efficiency for a HPGe detector.
AB  - The Monte Carlo method was used to determine full energy peak efficiency of a
      high-purity germanium (HPGe) co-axial detector within the energy range of 59.5
      1836 keV. Plotted ratios of the experimentally derived efficiency data over the
      fitted values showed oscillations at certain energies attributed to the
      characteristics of the detector. Results obtained by the Monte Carlo yielded
      deviations between 0.2 to 12% from the experimental data.

PMID- 11339524
TI  - Disequilibrium of uranium isotopes in some Syrian groundwater.
AB  - Uranium concentration in groundwater samples from three areas of Syria was
      determined using alpha-spectrometry and INAA. It was in the range of 0-6.13
      microg/l in the phosphate areas, and lower than 1 ppb in the volcanic areas. The
      activity ratio of 234U/238U was investigated, and disequilibrium of uranium
      isotopes was found to occur (234U/238U = 0.52-2.02). The excess of 234U was
      calculated. This excess can be interpreted by higher mobility of 234U, which more
      readily forms the soluble (UO2)2+ ion in comparison with 238U, most of which
      remains in the insoluble 4+ state. This excess increases with increase in uranium
      concentration. Thorium concentration was measured using INAA, it was found to be
      in the rang 0-1.15 microg/l.

PMID- 11339525
TI  - Diffusion of radon through varying depths of cement.
AB  - Portland cement was mixed with different concentrations of radium chloride (1200,
      2400 and 3600 Bq) to produce radioactive sources. These sources were surrounded
      with cement of different thickness (1, 2 and 4cm). The release of radon from
      these sources (before and after being surrounded) was studied. The results showed
      that radon release from the sources itself was less then its release from the
      same source after being surrounded by cement, and the release did not change with
      the thickness of cement. Samples were covered with a thin layer of polyethylene
      before being surrounded with cement. It was found that this additional layer
      reduced the radon exhalation. This thin layer stopped any reaction between the
      source and the surrounding cement during solidification of the cement layers.
      These reactions are thought to be the reason for the increase of radon exhalation
      from the sources surrounded by cement.

PMID- 11339526
TI  - Simulation of the skim-off method in radon measurement by activated charcoal.
AB  - Simulation of the skim-off method for radon measurement by activated charcoal has
      been carried out by the finite elements method. The variation of radon
      concentration with peak appearance has been simulated. The thickness of the layer
      of charcoal removed after exposure and the time of peak appearance have been
      varied. For the charcoal and canister geometry used, the best results were found
      when the thickness of the layer removed was 1.72 mm.

PMID- 11339527
TI  - Analysis of a discrepancy in electron-beam dose comparison between chemical
      dosimeters and a calorimeter.
AB  - A 2.1% discrepancy was reported from an electron-beam dose comparison between
      liquid chemical dosimeters and a water calorimeter. Two methods, depth-dose
      measurement in a sandwich phantom and the use of a semiempirical depth-dose code
      EDMULT, were used to analyze the depth-dose distribution in the dosimeters and
      the calorimeter and to calculate their dose ratio. Results have shown that the
      discrepancy can be explained by the difference in the effective detection volume.

PMID- 11339528
TI  - A low-level spectrometer with a planar low-energy HPGe: shielding arrangement
      tests and system performance for 210Pb determination in air filter samples.
AB  - A system for low-energy photon spectrometry using a planar germanium detector
      with appropriate specifications is presented. A spectrometric background
      investigation has been carried out with various detector shielding arrangements.
      The characteristics of the system for measurements of 210Pb in air-particulate
      matter on filters have been determined.

PMID- 11339529
TI  - Dosimetry of blood irradiation using an alanine/ESR dosimeter.
AB  - A batch of 80 DL-alanine dosimeters was supplied to Hemocentro of the Hospital
      and Clinics of Faculdade de Medicina de Ribeirao Preto (HC-FM RP) SP, Brazil for
      the purpose of quality control of the radiation dose delivered to blood bags. The
      irradiation was made using two (40 x 40) cm2 parallel opposed radiation fields
      each with 80 cm of source to surface distance in the Radiotherapy Section of HC
      FMRP with the 60Co teletherapy unit. The calculated radiation absorbed dose at
      the center of the box was 20 Gy. The dosimeter readings were performed using a
      Varian E-4 ESR Spectrometer operating in X-band. For the 80 dosimeters and over
      the irradiation volume throughout a blood bag, the minimum and maximum doses were
      14 and 23 Gy, respectively. The mean dose was (18 +/- 2) Gy (1sigma), and the
      coefficient of variability was 11.1%. Alanine dosimeters demonstrated easy
      handling, good precision and adequate sensitivity for this application.

PMID- 11339530
TI  - Characteristics of NORM in the oil industry from eastern and western deserts of
      Egypt.
AB  - Naturally occurring radionuclides (NORs) from the 232Th- and 238U-series, which
      are omnipresent in the earth's crust, can be concentrated by technical
      activities, particularly those involving natural resources. Although, a great
      deal of work has been done in the field of radiation protection and remedial
      action on uranium and other mines, recent concern has been devoted to the hazard
      arising from naturally occurring radioactive materials (NORM) in oil and gas
      facilities. NORM wastes associated with oil and gas operations from scale
      deposits, separated sludge and water at different oil fields in the eastern and
      western deserts were investigated. Concentrations of the uranium, thorium, and
      potassium (40K) series have been determined from high-resolution gamma-ray
      spectrometry. Total uranium content of samples was determined using laser
      fluorimetry. The levels of radioactivity were mainly due to enhanced levels of
      dissolved radium ions. Only minute quantities of uranium and thorium were
      present. The disequilibrium factor for 238U/226Ra has been determined.

PMID- 11339531
TI  - Assessment of radiation exposures from naturally occurring radioactive materials
      in the oil and gas industry.
AB  - Radioactive deposits, often referred to as naturally occurring radioactive
      material scale, can, because of incompatibility of formation and injection
      waters, be formed inside production equipment of the oil and gas industry. These
      scales contain mainly 226Ra and its daughter products, which can cause an
      exposure risk. The gamma ray dose rates, with the associated occupational doses
      in the oil and gas industry, and 226Ra concentration in production water, crude
      oil and hard/soft scale samples were determined. Results obtained are discussed
      and compared to those from other studies.

PMID- 11339532
TI  - A simple loop method for the automated preparation of (11C)raclopride from
      (11C)methyl triflate.
AB  - A simple automated preparation of [11C]raclopride by reaction of [11C]methyl
      triflate with demethylraclopride triflate is described. The conventional bubbling
      of [11C]methyl triflate into the precursor solution was compared with two
      alternative methods which used a commercially available C18 cartridge (on-column
      method) or an empty PTFE tube (loop method) as support for the precursor
      solution. The influence of several solvents was assessed for all three methods.
      The on-column method showed excellent trapping efficiencies of [11C]methyl
      triflate but gave the lowest radiochemical yields. The loop method proved to be a
      simplified alternative to the bubbling method, giving comparable radiochemical
      yields with less precursor and offering an easy way to transfer the reaction
      mixture into an HPLC column. By the simple-loop method [11C]raclopride could be
      prepared in over 40% radiochemical yields (decay-corrected and based on
      [11C]methyl triflate).

PMID- 11339533
TI  - Decay data: review of measurements, evaluations and compilations.
AB  - Decay data represent an important means of characterising and quantifying
      radioactive material, as well as providing an important route to our
      understanding of the structure of the nucleus. The principle decay parameters are
      defined in this review, prior to undertaking an applications-based assessment of
      the most relevant contemporary measurements, evaluations and compilations.
      Emphasis has been placed on the demands of a series of IAEA Co-ordinated Research
      Programmes that focus on decay data and gamma-ray standards. Some of the more
      important decay-data issues are also reviewed with respect to recent measurements
      that address the anomalies associated with intermediate- and long-lived
      radionuclides. Short-lived fission products pose significant characterisation
      problems due to their high degree of instability, although a combination of mass
      separation and complex detector arrays has resulted in rapid analyses and major
      advances in our understanding of their nuclear properties and structure. Finally,
      a select number of decay-data evaluations and compilations are discussed in terms
      of the powerful manipulation and communication capabilities of PCs, CD-ROMs and
      the Internet.

PMID- 11339534
TI  - The Chernobyl accident: EPR dosimetry on dental enamel of children.
AB  - The radiation dose on tooth enamel of children living close to Chernobyl has been
      evaluated by EPR. The sample preparation was reduced to a minimum of mechanical
      steps to remove a piece of enamel. A standard X-ray tube at low energy was used
      for additive irradiation. The filtration effect of facial soft tissue was taken
      into account. The radiation dose for a group of teeth slightly exceeds the annual
      dose, whereas for another group the dose very much exceeds the annual dose. Since
      the higher dose is found in teeth whose enamel have much lower EPR sensitivity to
      the radiation, it can be suggested that for these teeth the native signal could
      alter the evaluation of the smaller radiation signal.

PMID- 11339535
TI  - Calibration of monitors used for surveillance of radioactivity in effluent water
      from CERN's accelerator installations.
AB  - Water released into the environment from CERN's accelerator installations may
      contain both long-lived (7Be, 22Na) and short-lived (11C, 13N, 24Na) gamma
      radioactivity. Each potential release point is equipped with an on-line monitor
      for short-lived radionuclides, which consists of a scintillation probe immersed
      in a tank filled with monitored water. Whilst calibration standards are available
      for long-lived radioactivity, computer simulations are the only feasible way to
      determine the monitor efficiency for the short-lived radionuclides. The paper
      describes computer simulations using the Monte Carlo code GEANT 3.21. An
      excellent agreement between measured and computed efficiencies was obtained for
      the long-lived radionuclides, validating the computer model. A calibration method
      is proposed for light positron emitters, which combines an experimental
      calibration for 7Be and correction factors obtained in the simulations.

PMID- 11339536
TI  - Standardisation and decay data of 177Lu and 188Re.
AB  - The activity values of 177Lu and 188Re standard sources were measured using the
      4pibeta-gamma-coincidence method and by liquid scintillation counting. The X- and
      gamma-ray emission probabilities per disintegration were determined by means of
      photon spectrometry with calibrated Ge and Si(Li) detectors and using the
      pertinent activity values. The half-lives were measured with ionization chambers,
      yielding T(1/2)(177Lu) = 6.646(5) d and T(1/2)(188Re) = 0.70848(9) d.

PMID- 11339537
TI  - Thin film thickness determination with neutron activation analysis.
AB  - Thickness determination of Ta2O5 thin films, deposited on the glass substrates
      and metallic indium and gold thin films on both glass and aluminum substrates,
      were performed by neutron activation analysis. Thickness determination of these
      thin films were made by comparing gamma-rays emitted from the radio-isotopes in
      the thin film with the substrate material followed by the neutron irradiations.
      The method led to determination of the film thicknesses without using any
      standard sample. A complementary optical transmission measurement was also
      applied on multi-layered Ta2O5 thin films for determining the individual layer
      densities.

PMID- 11339538
TI  - Activity of (239 + 240)Pu and 238Pu in atmospheric deposits.
AB  - Radioactive concentrations of (239 + 240)Pu and 238Pu were determined in
      rainwater samples collected at Badajoz (in a semi-arid zone in the south-west of
      Spain) from 1992 to 1996. Total plutonium deposition (including dry and wet
      deposition) was investigated during dry and wet periods. Anomalously high
      depositions of (239 + 240)Pu ((6.8 +/- 0.4) mBq/m2) and 238Pu ((2.2 +/-
      0.2)mBq/m2) were found in the second-half of 1995. The 238Pu/(239 + 240)Pu
      activity ratio (0.32 +/- 0.04) obtained for that sample was higher than in global
      fallout.

PMID- 11339539
TI  - The current status of live attenuated varicella vaccine.
AB  - This manuscript reviews the means by which live attenuated varicella vaccine
      offers protection against varicella and zoster. It is accepted that although
      varicella is usually a mild illness, complications leading to morbidity and
      mortality are significant and the disease is worth preventing. The vaccine offers
      close to 100% protection from severe chickenpox and 90% protection from illness.
      Waning of immunity after vaccination, particularly in children, has not been a
      significant problem. Ways in which vaccination may decrease the incidence and
      severity of zoster include the following. Vaccine virus may be less likely to
      establish latency and to be able to reactivate than wild type virus. In addition,
      by selective immunization of certain hosts such as HIV-infected children whose,
      immune systems are still relatively intact and individuals with latency due to
      wild type virus to boost the cell-mediated immune response to the virus, zoster
      may be decreased. Varicella vaccine is predicted to have a major impact on the
      epidemiology of varicella and zoster in countries with high vaccine uptake.

PMID- 11339540
TI  - Pathway of viral spread in herpes zoster: detection of the protein encoded by
      open reading frame 63 of varicella-zoster virus in biopsy specimens.
AB  - Reactivation of varicella-zoster virus (VZV) in the dorsal root or trigeminal
      ganglia causes herpes zoster. The pathway of viral spread from the ganglia to the
      skin and also within the skin is not yet completely understood. Histological
      studies have revealed that each skin lesion in herpes zoster progresses
      sequentially through the stages of erythema, vesicles, pustules and finally
      ulceration. An immunohistochemical study of the early skin lesions of herpes
      zoster demonstrated a high incidence of hair follicle involvement and the main
      localization of the virus at the isthmus. This evidence suggests that VZV
      initially spreads from the ganglia through myelinated nerves, which predominantly
      end around the isthmus of hair follicles. To further investigate the viral spread
      within the skin, we analyzed the sequential appearance of the immediate early
      proteins encoded by ORF 63 of VZV (IE63), using an anti-IE63 antibody raised by
      immunization of rabbits with a recombinant protein. This antibody could detect
      IE63 in a western blot analysis of infected cells and also in immunohistochemical
      analysis of the skin lesions of herpes zoster. IE63 initially appeared in the
      nuclei of the follicular epithelial cells and basal or parabasal epidermal cells.
      Later, the nuclei and cytoplasm of cells in the epidermis and hair follicles
      became positive. IE63 remained in the virus-infected cells even during their
      degeneration. When we examined the hair follicles in the early erythematous
      lesions, cells positive for IE63 were predominantly distributed around the
      isthmus. In addition, some lymphocytes around the blood vessels were also
      positive for IE63, but these cells were seldom positive for the structural
      antigen. Thus, these observations suggest that VZV arriving through myelinated
      nerves infects not only permissive cells, but also non-permissive cells in the
      involved skin of herpes zoster.

PMID- 11339541
TI  - Vaccination against cytomegalovirus.
AB  - Like varicella zoster virus (VZV), human cytomegalovirus (HCMV) causes disease
      after both primary and recurrent infections. The former is more serious,
      particularly in pregnant women, who may transmit the virus to their offspring,
      with a high risk of mental retardation and deafness. Various experimental
      vaccines are in development, ranging from live, attenuated HCMV, subunit envelope
      glycoprotein, poxvirus vectors with CMV genes inserted, and plasmid DANN.

PMID- 11339543
TI  - In vitro measurement of human T cell responses to varicella zoster virus antigen.
AB  - Means to quantitate cell-mediated immunity are increasingly in demand as
      modifications to existing vaccines and new vaccines are tested. For immunity to
      varicella zoster virus, there is over a decade of experience with estimates of
      responder cell frequency obtained by diluting the number of lymphocytes in
      antigen-stimulated cultures. This method shows substantial variations between
      subjects, so populations of 12 or more subjects per group are needed to make
      comparisons possible. Cytokine-based methods for T lymphocyte responses may prove
      more sensitive, as may direct antigen-binding methods using tetramers of peptide
      and histocompatibility antigens--but experience with both is very limited.

PMID- 11339542
TI  - Varicella zoster virus in human and rat tissue specimens.
AB  - The limited supple of appropriate tissues for study has been an impediment to
      investigations of varicella zoster virus (VZV) latency. Human dorsal root ganglia
      (DRG) harboring latent virus are not plentiful and are not amenable to
      manipulation for studying the events surrounding the establishment, maintenance,
      and cessation of latency. An alternative to studies in human DRG is the rat model
      of latency, which appears to provide a reliable method of investigating VZV
      latency. Other alternatives include studies in other human tissues involved in
      VZV pathogenesis. In order to improve our understanding of the establishment and
      cessation of latency, we performed comparative immunohistochemical analysis of
      chickenpox and zoster skin lesions. This analysis revealed that during primary
      infection and reactivation productive VZV infection occurs in a variety of cell
      types and that the major VZV DNA binding protein, ORF29p, is present in
      peripheral axons early during the course of chickenpox. VZV latency was studied
      in the rat model by in situ hybridization and compared with similar studies
      performed in human DRG containing latent virus, confirming that VZV DNA persists
      in the same sites in DRG of the two species.

PMID- 11339544
TI  - Use of varicella vaccines to prevent herpes zoster in older individuals.
AB  - It is likely that the frequency and severity of herpes zoster in older people is
      the result of an age-related decline in varicella-zoster virus-specific T-cell
      mediated immunity. Numerous trials of vaccines to boost these responses have
      demonstrated their safety and immunogenicity. Both live attenuated and
      inactivated vaccines have been studied. Persistence of booster responses is dose
      related, and the half-life of some boosted measures of T-cell mediated immunity
      exceeds 5 years. Although these trials have been hampered by uncertainty about
      the critical immune responses to evaluate, the stage is set for a double-blind,
      placebo-controlled trial of sufficient size to determine efficacy. Such a trial
      is now underway.

PMID- 11339545
TI  - Immunization of the elderly to boost immunity against varicella-zoster virus
      (VZV) as assessed by VZV skin test reaction.
AB  - The utility of the VZV skin test in detecting individual susceptibility to
      varicella and zoster was determined. Its specificity particularly with regard to
      herpes simplex was also established. The VZV skin test was negative or weakly
      positive during the early stage of herpes zoster, and strongly positive during
      recovery from that disease. A small-scale clinical trial to immunize elderly
      individuals has been performed for the purpose of preventing herpes zoster, and,
      perhaps, severe post-herpetic neuralgia as well. Sixty individuals > or = 50
      years old were screened for VZV antibodies by IAHA test and were given a VZV skin
      test for cell-mediated immunity. All were seropositive, but eight were skin-test
      negative. Thirty-seven individuals including the eight with negative skin tests
      were immunized with one dose of varicella vaccine (3.0 x 10(4) PFU/dose). After 5
      7 weeks, the skin test reaction showed increased positivity, with a change in
      score from (-) to (+, ++) in 7/8 subjects, from (+) to (++, +++) in 3/5 subjects,
      and from (++) to (+++) in 6/10 subjects. Enhancement of the VZV antibody titer
      (defined as twofold or greater) was observed in all 15 vaccine recipients with a
      prevaccination titer of < or = 1:16, and in 19 of 24 subjects with a
      prevaccination titer of > or = 1:32. These results indicate that giving live
      varicella vaccine with a high viral titer can induce a good boost immunity
      particularly cell-mediated immunity to VZV in the elderly.

PMID- 11339546
TI  - Investigation of varicella-zoster virus variation by heteroduplex mobility assay.
AB  - Heteroduplex mobility assays of 37 regions were performed on ten UK isolates of
      varicella zoster virus, four from cases of zoster, and six from cases of
      chickenpox. The variation between isolates was found to be 0.061%, which is at
      least five times lower than any other member of the human herpesvirus family.
      Fifteen of the 37 regions tested had 29 single nucleotide polymorphisms, and over
      half the polymorphisms were located in four gene fragments. Of the 29 SNPs,
      eleven were non-synonymous and these were clustered in six genes. Isolates from a
      child and her mother to whom she had transmitted the virus, were identical at
      every locus tested. All other viruses could be distinguished by a combination of
      SNPs and length polymorphisms of the repeat regions R1, R2 and R5.

PMID- 11339547
TI  - Varicella-zoster virus immunity and prevention: a conference perspective.
AB  - This report offers a concise overview of the VZV Conference, highlighting recent
      developments in the field and speculating on areas of greatest opportunity and
      need for future work. The goal of eradicating VZV disease will be facilitated by
      a multifaceted research agenda directed at a fuller comprehension of how the
      virus replicates, spreads and persists, and how it eludes host immune responses.

PMID- 11339549
TI  - Biologic and geographic differences between vaccine and clinical varicella-zoster
      virus isolates.
AB  - Vaccine and wild-type strains of varicella-zoster virus differ both in their
      biologic characteristics and in the clinical manifestations of infection caused
      by each strain. The biologic differences described for the vaccine strain
      (temperature sensitivity and host cell preference) probably reflect the methods
      used to adapt the wild-type strain to the in vitro growth conditions imposed
      during the attenuation process in cell culture. In addition, restriction fragment
      polymorphisms have been described that reflect geographic strain variations
      between the parental virus used to develop the vaccine strain and other wild-type
      strains. These polymorphisms have been exploited as tools for the identification
      and differentiation of vaccine and wild-type strains in clinical studies.
      Infection with the wild-type strain results in the typical extensive rash of
      varicella, frequent transmission to other susceptible contacts, establishment of
      latency, and in some individuals, reactivation with the clinical picture of
      zoster. Infection with the vaccine strain results in the development of a
      protective immune response, minimal rash in a minority of individuals, rare
      transmission to other susceptible contacts, and a greatly reduced risk of zoster.

PMID- 11339548
TI  - Varicella-zoster virus with a lost gE epitope: evidence for immunological
      pressure by the human antibody response.
AB  - The varicella-zoster virus (VZV) genome contains about 70 open reading frames
      (ORF). ORF 68 codes for glycoprotein gE, formerly called gpl, which is the
      predominant VZV glycoprotein; gE is a typical type 1 transmembrane protein with
      623 amino acids. Recently, a variant virus was discovered which has a mutation in
      gE codon 150; this mutation converts an aspartic acid into an asparagine residue.

PMID- 11339550
TI  - Comparison of DNA sequence and transactivation activity of open reading frame 62
      of Oka varicella vaccine and its parental viruses.
AB  - When nucleotide sequences of Oka vaccine and its parental viruses of varicella
      zoster virus (VZV) were compared in 5 open reading frames (ORFs) including
      glycoprotein C (gC) and 4 immediate-early genes, mutations were detected only in
      gene 62 which is one of the immediate-early genes. Compared with its parental
      virus, the vaccine virus contained 15 nucleotide substitutions. With the
      differentiation method using the simplified restriction-enzyme fragment length
      polymorphism analysis by Nae I and Bss HII, which was established based on the
      sequence analysis data in this study, the Oka vaccine virus could be
      distinguished from its parental virus. Studies of the regulatory activities of
      the ORF62 gene product (IE62) in a transient assay indicate the IE62 of the
      parental virus had a stronger transactivational activity than that of the vaccine
      virus against immediate-early, early and late gene promoters. These data suggest
      that gene 62 might have an important role for attenuation of VZV. This is the
      first report in which many substitutions of nucleotides in gene 62 of Oka vaccine
      virus was found, compared with that of Oka parental virus.

PMID- 11339551
TI  - Cis and trans elements regulating expression of the varicella zoster virus gI
      gene.
AB  - We have identified cis- and trans-acting elements involved in the VZV IE62
      protein-activated expression of the varicella zoster virus (VZV) gene which
      encodes the viral gI glycoprotein. The cis-acting elements include a non
      canonical TATA box and a novel 19 base pair sequence located just upstream of the
      TATA element designated the "activating upstream sequence" or AUS. The AUS is a
      movable element and its presence results in IE62 activation of a chimeric
      promoter consisting of the VZV gC TATA box and the gI AUS. We have also
      determined that the VZV ORF 29 protein modulates the regulatory activity of the
      IE62 protein at the gI promoter. In combination with the IE62 transactivator, it
      yields a 10 to 15-fold increase in expression over the levels seen with the IE62
      protein alone in T lymphocytes. The upmodulatory activity requires the presence
      of a 40 base pair sequence, designated the 29RE, which maps between positions 
      220 and -180 in the gI promoter. In this paper we review these and earlier
      findings from our laboratories concerning the regulation of the gI promoter.

PMID- 11339552
TI  - Evidence for frequent reactivation of the Oka varicella vaccine strain in healthy
      vaccinees.
AB  - Serum antibody levels and infection rates were followed for 4 years in 4,631
      children immunized with the recently licensed Oka strain varicella vaccine. Anti
      VZV titers declined over time in high-responder subjects, but rose in vaccinees
      with low titers. Among subjects with low anti-VZV titers, the frequency of
      clinical sequelae and immunological boosting significantly exceeded the 13%/yr
      rate of exposure to wild type varicella. These findings indicate that the Oka
      strain of VZV persisted in vivo, and reactivated as serum antibody titers
      declined after vaccination. This mechanism may improve vaccine-associated long
      term immunity.

PMID- 11339553
TI  - Interactions among structural proteins of varicella zoster virus.
AB  - Varicella zoster virus tegument components include the regulatory proteins IE4,
      IE62, IE63 and the ORFI0 protein, a protein kinase (ORF47) and an abundant
      protein encoded in ORF9 which is the homolog of HSV VP22. The kinase is able to
      phosphorylate IE62 and the ORF9 protein specifically in viral particles. We show
      that interactions among these proteins are, at least in part, dependent on the
      presence or absence of phosphate groups and we suggest models for tegument
      formation and for its dissolution in the infected cell.

PMID- 11339554
TI  - The role of varicella zoster virus immediate-early proteins in latency and their
      potential use as components of vaccines.
AB  - Varicella zoster virus immediate-early (IE) proteins are intracellular regulators
      of viral gene expression. Some of them (IE62 and IE63) are found in large amounts
      in infected cells but are also components of the virion tegument. Several IE and
      early genes are transcribed during latency, while late genes are not. Recently,
      we demonstrated the presence of protein IE 63 in dorsal root ganglia of
      persistently infected rats as well as in normal human ganglia; other IE proteins
      have been found since in human ganglia. Cell-mediated immunity (CMI) to IE 62 has
      been evidenced. We found both humoral immunity and CMI to IE 63 in immune adults.
      In elderly zoster-free individuals, CMI to IE 63 remained high. The differences
      in the CMI to IE 63 among young adults, elderly people and immunocompromized
      patients have to be analyzed according to their status relative to zoster, to
      determine whether the decrease in CMI, particularly to IE proteins, could be
      responsible for viral reactivation and for the onset of shingles. Hopefully, the
      waning of the CMI to VZV IE 63 and perhaps to other IE proteins could become a
      predictive marker for herpes zoster and reimmunization, not only with the vaccine
      strain, but also with purified IE proteins could help prevent zoster at old age.

PMID- 11339555
TI  - Mutagenesis of the varicella-zoster virus genome: lessons learned.
AB  - The varicella-zoster virus (VZV) genome encodes at least 70 genes. We have
      developed a cosmid based system to inactivate individual viral genes or to insert
      foreign genes into the genome. We have shown that many VZV genes are not required
      for replication of the virus in cell culture. Several of these genes, including
      VZV ORF61, ORF47, and ORF10, have unexpected phenotypes in cell culture and
      differ from their homologs in the better studied herpes simplex virus (HSV). We
      have also used the Oka strain of VZV as a live virus vaccine vector. Guinea pigs
      vaccinated with recombinant VZV expressing HSV-2 glycoprotein D and challenged
      with HSV-2 have reduced severity of primary genital herpes and reduced mortality
      compared to animals receiving parental VZV. Recently we have inserted the human
      immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) glycoprotein
      160 genes into the Oka strain of VZV and have shown that these proteins are
      expressed in recombinant virus-infected cells. Thus, directed mutagenesis of the
      VZV genome is providing new insights into viral pathogenesis and may provide new
      candidate vaccines.

PMID- 11339556
TI  - Immune evasion mechanisms of varicella-zoster virus.
AB  - Varicella-zoster virus can to modulate the expression of class I and class II
      major histocompatibility (MHC) molecules. MHC class I expression is downregulated
      in VZV-infected T cells as well as in fibroblasts. VZV-infected cells do not
      respond to exposure to interferon-gamma (IFN-gamma) by upregulation of MHC class
      II expression. However, MHC class II expression is induced when cells are treated
      with IFN-gamma before VZV infection. These effects on MHC class I and class II
      expression can be expected to interfere transiently with adaptive immune
      responses of the host, mediated by CD4 and CD8 T cells, ensuring that the virus
      has sufficient opportunity for transmission to susceptible contracts.

PMID- 11339557
TI  - Recent developments and present status of telepathology.
AB  - Telepathology which is the diagnostic work of a pathologist at a distance has
      been developed to routine application within the last ten years. It can be
      classified in relation to application, technical solutions, or performance
      conditions. Diagnostic pathology performance distinguishes primary diagnosis (for
      example, frozen section statement) from secondary diagnosis (for example, expert
      consultation) and quality assurance (diagnostic accuracy, continuous education
      and training). Applications comprise (a) frozen section service; (b) expert
      consultations; (c) remote control measurements; and (d) education and training.
      The technical solutions distinguish active (remote control, live imaging) systems
      from passive (conventional microscope handling, static imaging), and the
      performance systems with interactive (on-line, live imaging) use from those with
      passive (offline, static imaging) practice. Intra-operative frozen section
      service is mainly performed with remote control systems; whereas expert
      consultations and education/training are commonly based upon Internet connections
      with static imaging in an off-line mode. The image quality, transfer rates, and
      screen resolution of active and passive telepathology systems are sufficient for
      an additional or primary judgment of histological slides and cytological smears.
      From the technical point of view, remote control telepathology requires a fast
      transfer and at least near on-line judgement of images, i.e., image acquisition,
      transfer and presentation can be considered one performance function. Thus, image
      size, line transfer rate and screen resolution define the practicability of the
      system. In expert consultation, the pixel resolution of images and natural color
      presentation are the main factors for diagnostic support, whereas the line
      transfer rate is of minor importance. These conditions define the technical
      compartments, especially size and resolution of camera and screen. The
      performance of commercially available systems has reached a high quality
      standard. Pathologists can be trained in a short time and use the systems in a
      routine manner. Several telepathology systems have been implemented in large
      Institutes of Pathology which serve for frozen section diagnosis in small
      hospitals located in the local area. In contrast, expert consultation is mainly
      performed with international connections. There is a remarkable increase of
      expert consultations by telepathology according to the experiences of the Armed
      Forces Institute of Pathology or the Department of Pathology, Thoraxklinik,
      Heidelberg. In expansion of these experiences, a "globalization" of telepathology
      can be expected. Telepathology can be used to shrink the period necessary for
      final diagnosis by request for diagnostic assistance to colleagues working in
      appropriate related time zones. Telepathology is, therefore, not a substitute of
      conventional diagnostic procedures but a real improvement in the world of
      pathology.

PMID- 11339558
TI  - Technical aspects of telepathology with emphasis on future development.
AB  - Pathology undergoes presently changes due to new developments in diagnostic
      opportunities and cost saving efforts in health care. Out of the wide field of
      telepathology the paper selects three prototype applications: telepathology in
      teleeducation, expert advice for preselected details of a slide and finally
      telepathology for remote diagnosis. The most challenging field for remote
      diagnosis is the application in the frozen section scenario. The paper starts
      with the mental experiment to map conventional procedures to counterparts in
      telepathology. Technical opportunities and economical restrictions of
      telepathology equipment are discussed with respect to the components: electronic
      camera, display devices, haptic sensors and displays, available telecommunication
      channels and telepathology software. As an example and for illustration of the
      state of the art for an advanced telemicroscopy system able to perform remote
      frozen section diagnosis, the HISTKOM equipment is presented in more details. The
      section concerning future developments regards the aspects of the acceptance by
      tentative users, legal aspects, costs and affordability of equipment, the market
      for equipment components and the adequate telecommunication services. Further is
      regarded the mutual influence of properties of existing systems and application
      experiences gained with them on the next generation of equipment and application
      software. Conclusions and references close the paper.

PMID- 11339559
TI  - Current experiences with internet telepathology and possible evolution in the
      next generation of Internet services.
AB  - The last five years experience has definitely demonstrated the possible
      applications of the Internet for telepathology. They may be listed as follows:
      (a) teleconsultation via multimedia e-mail; (b) teleconsultation via web-based
      tools; (c) distant education by means of World Wide Web; (d) virtual microscope
      management through Web and Java interfaces; (e) real-time consultations through
      Internet-based videoconferencing. Such applications have led to the recognition
      of some important limits of the Internet, when dealing with telemedicine: (i) no
      guarantees on the quality of service (QoS); (ii) inadequate security and privacy;
      (iii) for some countries, low bandwidth and thus low responsiveness for real-time
      applications. Currently, there are several innovations in the world of the
      Internet. Different initiatives have been aimed at an amelioration of the
      Internet protocols, in order to have quality of service, multimedia support,
      security and other advanced services, together with greater bandwidth. The
      forthcoming Internet improvements, although induced by electronic commerce, video
      on demand, and other commercial needs, are of real interest also for
      telemedicine, because they solve the limits currently slowing down the use of
      Internet. When such new services will be available, telepathology applications
      may switch from research to daily practice in a fast way.

PMID- 11339560
TI  - Acceptance of telepathology in daily practice.
AB  - The availability of pathology services differs greatly in our environment.
      Although pathology would be especially suitable for being practised at a distance
      by transporting digital image information, the spread of telepathology into
      everyday work still is relatively slow. The article describes the situation of
      diffusion of this innovative technology by reviewing the literature and
      discussing this in context to data based on questionnaires dealing with the
      acceptance of telepathology. The current situation of telepathology can be
      discussed by five items for innovation spead: (1) communication and influence;
      (2) economic costs and benefits; (3) knowledge barriers and learning; (4)
      feasibility of techniques offered for the demands of the users; (5) clarification
      of the legal status and other factors concerning international collaboration. All
      these head lines do not represent realistic obstacles for the more widespread use
      of telepathology. The real drawbacks may therefore be found behind certain
      professional habits of pathologists. The most important causes may be that (a)
      telediagnosis is not as easy as it may seem at the first glance; (b)
      telepathology is seen as a potential highway to a world-wide competition of
      pathology service providers. As soon as these mostly unjustified prejudices are
      corrected and telepathology is percepted as additional technique in pathology, it
      will become a diagnostic tool as common and as useful as the telephone.

PMID- 11339561
TI  - Informational aspects of telepathology in routine surgical pathology.
AB  - Application of computer and telecommunication technology calls serious challenges
      in routine diagnostic pathology. Complete data integration, fast access patients'
      data to usage of diagnosis thesaurus labeled with standardized codes and free
      text supplements, complex inquiry of the data contents, data exchange via
      teleconsultation and multilevel data protection are required functions of an
      integrated information system. Increasing requirement for teleconsultation
      transferring a large amount of multimedia data among different pathology
      information systems raises new questions in telepathology. Creation of complex
      telematic systems in pathology requires efficient methods of software engineering
      and implementation. Information technology of object-oriented modeling, usage of
      client server architecture and relational database management systems enables
      more compatible systems in field of telepathology. The aim of this paper is to
      present a practical example how to unify text based database, image archive and
      teleconsultation in a frame of an integrated telematic system and to discuss the
      main conceptual questions of information technology of telepathology.

PMID- 11339562
TI  - A telepathology based Virtual Reference and Certification Centre for DNA image
      cytometry.
AB  - An increasing need for flexible consultation between pathologists, including the
      application of fast evolving supplementary technologies, has been identified
      during the last years. Although pathology is already one of the most advanced
      application of telemedicine there is more to come from the fast evolution towards
      computerized microscope image analysis: A reproducible quantification of
      measurable descriptors of the lesions in cells and tissues (so-called biological
      markers) is an indispensable adjunct to routine diagnostic application. Among
      such quantitative methods DNA image cytometry is increasingly applied by
      pathologists for assistance in diagnostics. As for other pathological issues,
      too, a reference center for the clinical application of DNA image cytometry might
      be therefore of utmost value for pathologists using that method. Based on
      advanced telematic technologies, a Virtual Reference and Certification Center
      (VRCC) could be installed for certifying the cytometry hardware and software, the
      analytical procedures, and the basic interpretation of the results. It will be
      designed to be operated as a non-attended service, based on quantification
      servers accessible via Internet round the clock. The VRCC will supply appropriate
      standardization and normalization materials and run a GroupWare platform for
      consensus making by experts.

PMID- 11339563
TI  - Comparison of different telepathology solutions for primary frozen section
      diagnostic.
AB  - In a retrospective study on a set of 125 cases we compared the following three
      telepathology solutions for primary frozen section diagnosis: ATM-TP (connection
      via ATM), TPS 1.0 (connection via LAN) and TELEMIC (connection via Internet),
      which represent different concepts of telepathological procedures. A set of 125
      routine frozen sections (breast) was selected from the Charite cases of the year
      1999. Four experienced pathologists diagnosed retrospectively all of these cases
      using the ATM-TP and TPS systems and 53 of them with the TELEMIC system. Using
      the ATM-TP we recorded no false positive (0%), 4 false negative (3.2%) and 4
      deferred (3.2%) cases. Using the TPS we recorded no false positive (0%), 4 false
      negative (3.2%) and 4 deferred (3.2%) cases. Using the TELEMIC we recorded in 53
      cases no false positive (0%), no false negative (0%) and 16 deferred (30.2%)
      cases. The average time of 2.2 minutes per case using ATM-TP is also short enough
      for routine frozen section diagnostic. This is also true for the TPS system with
      7.2 minutes per case.

PMID- 11339564
TI  - Experience with a dynamic inexpensive video-conferencing system for frozen
      section telepathology.
AB  - AIM: To evaluate the feasibility of an inexpensive, generally applicable video
      conferencing system for frozen section telepathology (TP). METHODS: A
      commercially widely available PC-based dynamic video-conferencing system (Picture
      Tel LIVE, model PCS 100) has been evaluated, using two, four and six ISDN
      channels (128-384 kilobits per second (kbs)) bandwidths. 129 frozen sections have
      been analyzed which were classified by TP as benign, uncertain (the remark
      probably benign, or probably malignant was allowed), malignant, or not acceptable
      image quality. The TP results were compared with the original frozen section
      diagnosis and final paraffin diagnosis. RESULTS: Only 384 kbs (3 ISDN-2 lines)
      resulted in acceptable speed and quality of microscope images, and synchronous
      image/speech transfer. In one of the frozen section cases (0.7%), TP image
      quality was classified as not acceptable, leaving 128 frozen sections for the
      analysis. Five of these cases were uncertain by TP, and also deferred by frozen
      section procedure (FS). One more benign and three malignant FS cases were
      classified as uncertain by TP. Three additional cases were uncertain by FS, but
      benign according to TP (in agreement with the final diagnosis). In one case, FS
      diagnosis was uncertain but TP was malignant (in agreement with the final
      diagnosis). Thus, test efficiency (i.e., cases with complete agreement) was
      120/128 (93.8%, Kappa = 0.88) between FS and TP. Sensitivity was 93.5%,
      specificity 98.6%, positive and negative predictive values were 97.7% and 96.0%.
      Between TP and final diagnosis agreement was even higher. More importantly, there
      was not a single discrepancy as to benign-malignant. Moreover, there was a clear
      learning effect: 5 of the 8 FS/TP discrepancies occurred in the first 42 cases
      (5/42 = 11.9%), the remaining 3 in the following 86 cases (3/86 = 3.5%).
      DISCUSSION: The results are encouraging. However, TP evaluation is time-consuming
      (5-15 min for one case instead of 2-4 min although speed went up with more
      experience) and is more tiring. The system has the following technical drawbacks:
      no possibility to point at objects or areas of interest in the life image at the
      other end, resolution (rarely) may become suboptimal (blocky), storage of images
      evaluated (which is essential for legal reasons) is not easy and no direct
      control of a remote motorized microscope. Yet, all users were positive about the
      system both for telepathology and personal contact by video-conferencing.
      CONCLUSION: With a relatively simple videoconferencing system, accurate dynamic
      telepathology frozen section diagnosis can be obtained without false positive or
      negative results, although a limited number of uncertain cases will have to be
      accepted.

PMID- 11339565
TI  - How could static telepathology improve diagnosis in neuropathology?
AB  - The present paper reports our experience with, and our opinion of static
      telepathology as applied to neuropathology by means of the PHAROS acquisition
      system and conventional telephone data transmission (modem). The classical
      procedure of expert consultation based on surface mailing of histological slides
      is routinely performed, especially in highly specialized fields of pathology.
      Telepathology is an easy means of sharing scientific expertise at international
      level and could thus improve diagnosis particularly in neuropathology, where
      certain tumor types are very rare and complex to diagnose. Dynamic telepathology
      allows the referring pathologist to capture by himself images supporting their
      diagnosis. Using static telepathology the pathologist could be limited in
      diagnosis by problems in fields selection. We devoted a whole year to collecting
      all the technical parameters characterizing the use of digitized
      neuropathological data files in order to investigate the feasibility of
      telepathology and the extent to which its use could improve diagnoses. Our
      results on a series of 38 histological brain examinations illustrate how we
      successfully established an international connection between two departments of
      pathology in Belgium and the USA. The referring pathologists gave diagnoses in 35
      cases and deferred only 3. Despite a time-consuming procedure for the
      telepathology session of a few cases, this tool provides easy access to expert
      diagnosis and real-time discussion, both of which are of considerable interest
      and offer significant improvements in neuropathology.

PMID- 11339566
TI  - Teleeducation and telepathology for open and distance education.
AB  - Our experience in creating and using telepathology system and multimedia database
      for education is described. This program packet currently works in the Department
      of Pathology of University Medical School in Poznan. It is used for self
      education, tests, services and for the examinations in pathology, i.e., for
      dental students and for medical students in terms of self-education and
      individual examination services. The system is implemented on microcomputers
      compatible with IBM PC and works in the network system Netware 5.1. Some modules
      are available through the Internet. The program packet described here
      accomplishes the TELEMIC system for telepathology, ASSISTANT, which is the
      administrator for the databases, and EXAMINATOR, which is the executive program.
      The realization of multi-user module allows students to work on several working
      areas, on random be chosen different sets of problems contemporary. The
      possibility to work in the exercise mode will image files and questions is an
      attractive way for self-education. The standard format of the notation files
      enables to elaborate the results by commercial statistic packets in order to
      estimate the scale of answers and to find correlation between the obtained
      results. The method of multi-criterion grading excludes unlimited mutual
      compensation of the criteria, differentiates the importance of particular courses
      and introduces the quality criteria. The packet is part of the integrated
      management information system of the department of pathology. Applications for
      other telepathological systems are presented.

PMID- 11339567
TI  - Telepathology: design of a modular system.
AB  - Although telepathology systems have been developed for more than a decade, they
      are still not a widespread tool for routine diagnostic applications. Lacking
      interoperability, software that is not satisfying user needs as well as high
      costs have been identified as reasons. In this paper we would like to demonstrate
      that with a clear separation of the tasks required for a telepathology
      application, telepathology systems can be built in a modular way, where many
      modules can be implemented using standard software components. With such a
      modular design, systems can be easily adapted to changing user needs and new
      technological developments and it is easier to integrate modular systems into
      existing environments.

PMID- 11339568
TI  - Diagnostic errors in interactive telepathology.
AB  - Telepathology (TP) as a service in pathology at a distance is now widely used. It
      is integrated in the daily workflow of numerous pathologists. Meanwhile, in
      Germany 15 departments of pathology are using the telepathology technique for
      frozen section service; however, a common recognised quality standard in
      diagnostic accuracy is still missing. In a first step, the working group Aurich
      uses a TP system for frozen section service in order to analyse the frequency and
      sources of errors in TP frozen section diagnoses for evaluating the quality of
      frozen section slides, the important components of image quality and their
      influences an diagnostic accuracy. The authors point to the necessity of an
      optimal training program for all participants in this service in order to reduce
      the risk of diagnostic errors. In addition, there is need for optimal cooperation
      of all partners involved in TP service.

PMID- 11339569
TI  - Telediagnosis of transbronchial fine needle aspirations--a feasibility study.
AB  - AIM: To analyze the diagnostic accuracy of telediagnostic procedures for
      transbronchial fine needle aspirations. MATERIAL AND METHODS: A double blind
      study was performed on cytological slides of 54 randomly selected cases with
      transbronchial fine needle aspirations. The slides were digitized using a Leica
      digital camera DC100 mounted on a microscope Leica Laborlux S, and analyzed by an
      experienced pathologist without knowing the definite diagnosis or any additional
      clinical data. The diagnoses stated by analyzing the digital images were compared
      to the final conventional diagnoses. In addition, the duration of the digital
      diagnosis, used magnifications, and difficulties for correct sampling were
      documented. RESULTS: The "digital" diagnoses of the 54 cases were all in general
      agreement with the definite diagnoses. No wrong positive or wrong negative case
      in respect to malignant/non-malignant (31/23) or to small cell/non-small cell
      (9/22) occurred. The performance of a digital diagnosis lasted for 115 s at
      average (15-260 s), and is significantly longer compared to that of conventional
      fine needle aspiration judgement (20 s). The screening magnification was commonly
      set to x2.5, that for definite diagnostic analysis x40. Benign diseases (2
      tuberculosis and 3 sarcoidosis cases) were correctly classified. CONCLUSIONS:
      Telepathology systems can probably be used for fine needle aspiration analysis
      without major diagnostic errors. Their use can improve the endoscopic sampling
      and avoid second anesthesia when missing the lesion of request during the first
      examination.

PMID- 11339570
TI  - Reliability of telepathology for frozen section service.
AB  - One of the most promising applications of telepathology (pathology at a distance
      by electronic transmission of images in pathology) is frozen section diagnosis,
      especially because by means of this tool operations requiring an intraoperative
      histopathological diagnosis are feasible at hospitals without a pathologist on
      site. For the introduction of this diagnostic tool into pathologist's daily
      practice the evidence of its diagnostic accuracy comparable to that of the
      conventional frozen section diagnosis is crucial. For this purpose the literature
      on the diagnostic accuracy of telepathological frozen section diagnosis was
      reviewed. In a metaanalysis these studies and reports, in which a total of more
      than 1290 cases had been examined, showed a slightly lower overall diagnostic
      accuracy (of the telepathological frozen section diagnosis) of about 0.91 than
      the conventional frozen section diagnosis with an average accuracy of about 0.98
      found in an analysis of several studies (on frozen section diagnosis of different
      organs). This difference is at least predominantly caused by a higher rate of
      deferred and false negative frozen section diagnoses in the telepathological
      method, while the specificity of both methods, each more than 0.99 was not
      significantly different. In conclusion, the introduction of a telepathological
      frozen section diagnosis for hospitals without an acceptable access to a
      pathologist is justifiable already at the current state of the technological
      development especially when considering the advantages (time saving, reduction in
      costs) compared to the alternative of surgical interventions without access to an
      intraoperative diagnosis.

PMID- 11339571
TI  - The telepathology and teleradiology network in Croatia.
AB  - Telepathology as a demanding branch of telemedicine poses a real challenge to
      experts. The introduction of telepathology in underprivileged countries with poor
      infrastructure and low health-care budget is a difficult task. On the other hand
      these countries would mostly benefit by introducing telemedicine/telepathology.
      In our experience it is possible to build an efficient
      telepathology/teleradiology network using analogue telephone links and still
      image transmission, and a store and forward mode of operation. This experience is
      based on the application of telepathology in Croatia for seven years leading to a
      national teleradiology network. In this paper the ideas, development and software
      solutions in the process of establishing a national telepathology and
      teleradiology network are highlighted.

PMID- 11339572
TI  - Diagnosis of congenital heart malformations--possibilities for the employment of
      telepathology.
AB  - GOAL: In a study of 10 autopsy cases with congenital cardiac malformations we
      investigated whether obtaining a second opinion by means of telepathology could
      satisfy quality standards for the diagnosis of cardiac malformations and what the
      advantages and disadvantages of such a procedure might be. MATERIAL: The
      investigatory samples were 10 formalin-fixed hearts with complex malformations
      from 9 fetuses and one newborn on which autopsies had been performed at the
      Pathological Institute of the Charite Hospital. The requests for a second
      opinion, which included text and image data, were sent in the form of Microsoft
      PowerPoint presentations to 5 experts in 4 countries. Per case the number of
      images that were sent was between 3 and 7. The size of the files was between 439
      and 942 kb. The time required for preparation of the cases for sending them to
      the specialists was between 1 and 2 hours: this encompassed the time for putting
      the notation on the images, compressing them, creating a file that included both
      the images and the clinical data and then sending the case file. RESULTS: All 10
      cardiac malformations were correctly identified. In 8 of the 10 cases at least
      one expert had questions. After these questions had been answered and further
      images had been sent final correct diagnoses were made in all cases. All experts
      said that the quality of the images was very good. Use of a standardized findings
      questionnaire, which also included the marking of anatomic structures and of
      pathological findings in the images, proved useful. Standardized findings forms
      facilitate orientation during interpretation of the cases and should be used
      generally to avoid misunderstandings in telepathological communication.
      CONCLUSIONS: In general it is possible to obtain an effective and reliable
      diagnosis of congenital heart malformations by means of telepathology. It is far
      quicker to get a second opinion by this means than by conventional means.

PMID- 11339573
TI  - Telepathology in Europe.

PMID- 11339574
TI  - Legal aspects of telepathology.
AB  - In some legal surroundings telepathology is considered a breach of registrational
      barriers. The recommendation of the G 8 states in Europe for required legislation
      in telemedicine suggests to recognise that the localization of the remote health
      care professional defines the site not only of licensure but also of liability.
      This approach must be considered helpful, since it can solve many problems
      brought about by the doubtful results of private international law and
      conventions like the European Union (EU) and Lugano Convention. Under today's
      conditions in private international law it must be considered essential to agree
      upon a choice of law and stipulate a court of jurisdiction when doing
      telepathology. However, the opposing aims of insuring the patients claims and
      avoiding jurisdictions that exceed the local expectations of the medical
      professional must be reconciled. Data protection and data security are other
      crucial topics that require attention. Generally speaking, the principles of
      minimum data exchange, anonymity, pseudonymity and cryptography must be
      established as a basis for all telepathology procedures. Only when personal data
      is needed, its use can be legitimated. Written consent of the patient is advised.
      To guarantee a cross-border security level the regulations of the EU-Data
      Protection Directive need to be transformed into national law. In practise, cross
      border dataflow shall only take place where the security level can be maintained
      even within the other country. Finally, reimbursement questions must be answered
      to establish a sound economical basis for telepathology. The spatial distance
      between the participants may yield the question, whether the service has been
      rendered to an extent necessary and sufficient for reimbursement. If
      reimbursement takes place on a cross-border or cross-regional level, severe
      disturbances of the health systems can occur. Regulation schemes or treaties need
      therefore to be developed to avoid such disturbances and encompass mutual
      standards of care as well as methods to balance reimbursement.

PMID- 11339575
TI  - Improving glaucoma filtering surgery.

PMID- 11339576
TI  - Surgical removal of subfoveal choroidal neovascular membranes.

PMID- 11339577
TI  - Surgical removal of choroidal neovascular membranes after laser photocoagulation
      for diabetic maculopathy.
AB  - PURPOSE: Choroidal neovascularisation (CNV) occurs rarely following laser
      photocoagulation for macular oedema in diabetic retinopathy, and its management
      is not well established. We report the clinical course and visual outcomes in a
      series of patients who underwent surgical extraction of the CNV membrane.
      METHODS: A retrospective review of 4 cases was carried out. RESULTS: Two women
      and 2 men, mean age 59.5 (range 58-62) years, were reviewed. The CNV developed 2
      24 (mean 11) months after laser coagulation and resulted in decreased visual
      acuity to between 6/60 and HM. All underwent pars plana vitrectomy, extraction of
      the CNV membrane and fluid-air exchange. Follow-up ranged between 9 and 48
      months. In 2 patients, the vision improved by 4 and 1 Snellen lines respectively
      and remained stable, in 1 patient it improved by 1 line initially but then
      regressed to CF, and in 1 patient it remained unchanged. Recurrence of CNV
      occurred in only 1 patient. Histological characteristics were those of CNV
      without evidence of photoreceptors. CONCLUSIONS: This study shows that surgical
      removal of post-laser CNV is technically feasible despite the previous laser
      scars and may have beneficial outcome. This surgical approach may provide a
      therapeutic option in such patients.

PMID- 11339578
TI  - Transvitreal fine needle aspiration biopsy: the influence of intraocular lesion
      size on diagnostic biopsy result.
AB  - PURPOSE: To determine the efficacy of transvitreal biopsy in the diagnosis of
      suspected intraocular malignancy and simulating conditions. METHODS: We performed
      a retrospective study of the case notes from patients who underwent pars plana
      transvitreal biopsy from July 1986 to October 1999. We studied the relationship
      between lesion thickness as measured by A-scan ocular ultrasound and the
      incidence of a successful diagnostic biopsy. We assessed the diagnostic accuracy
      by comparing the biopsy result with the histological examination of any
      subsequently enucleation specimens and noted the incidence and severity of
      complications attributable to the biopsy. RESULTS: A total of 83 biopsies were
      performed for choroidal masses. There was insufficient material for cytological
      examination in 10 cases, and sufficient material in 73 cases (an overall
      diagnostic report rate was 88%). There was a strong correlation (p = 0.0004, Mann
      Whitney U-test) between a diagnostic biopsy result and the thickness of the
      lesion on A-scan ultrasound: a biopsy was diagnostic in only 40% (4 of 10) of
      choroidal lesions less than 1.99 mm thick, whereas biopsies taken from lesions
      between 2.00 and 4.00 mm thick were diagnostic in 90% of cases (27 of 30). In
      thicker lesions of 4 mm or more the cell aspirate was sufficient to make a
      diagnosis in 98% (42 of 43). Following diagnostic biopsy 27 patients had their
      tumours resected, and the histology results following enucleation confirmed the
      cytological diagnosis of malignancy in 96% of these cases (26 of 27). CONCLUSION:
      Transvitreal biopsy is a highly accurate diagnostic procedure with a low
      complication rate. It is a reliable diagnostic tool in suspicious choroidal
      lesions greater than 2 mm thick.

PMID- 11339579
TI  - Eclipse retinopathy.
AB  - PURPOSE: Solar retinopathy is a well-recognised clinical entity of macular damage
      caused by viewing the sun, induced by a photochemical process. The term 'eclipse
      retinopathy' is frequently employed when the condition is sustained as a result
      of viewing a solar eclipse. Considerable public excitement had been raised in
      anticipation of the full solar eclipse on 11 August 1999. Whilst experience has
      shown that visual morbidity is likely to be temporary, current evidence is
      anecdotal and restricted to isolated case reports and series. This study was
      conducted to establish the true visual morbidity associated with a solar eclipse,
      and whether it was temporary or permanent. METHODS: A 3 month active case
      ascertainment study was carried out from July to September 1999 to record cases
      presenting to ophthalmologists with visual symptoms arising from solar viewing.
      Further information about the cases was sought using a short questionnaire. A
      follow-up questionnaire requesting outcome data at 6 months was also employed.
      RESULTS: There were 70 reported cases of visual loss. The average age was 29.5 +/
      12.9 years. Half the cases presented to an ophthalmologist within 2 days of the
      eclipse. An abnormal macular appearance was reported in 84% of patients at
      presentation. There have been no reported cases of continued visual loss or
      symptoms at 6 months. CONCLUSIONS: This is the largest nationwide study of the
      visual effects of a solar eclipse ever undertaken. There were no recorded cases
      of permanent visual loss, which corroborates the previous evidence that visual
      morbidity is likely to be temporary. It would appear probable that public health
      education was most effective in reducing visual morbidity and hence keeping the
      consequent burden on the NHS to a minimum.

PMID- 11339580
TI  - The influence of counselling on patient return following uncomplicated posterior
      vitreous detachment.
AB  - PURPOSE: To investigate the effect of patient counselling together with the use
      of information leaflets on the number of return visits for patients with acute,
      symptomatic, uncomplicated posterior vitreous detachment (PVD). METHODS: The
      study group comprised the first 50 patients diagnosed with uncomplicated PVD in
      1998 when a standard protocol of structured patient counselling and leaflet
      distribution was employed following diagnosis of PVD. The control group comprised
      the first 50 patients in 1997 diagnosed with uncomplicated PVD before structured
      patient counselling was in place. A retrospective analysis of casualty case notes
      was made comparing the two groups. The number of eye casualty attendances within
      1 year of first presentation with PVD was compared in the two groups. RESULTS:
      Seven patients from the control group returned because of photopsia or floaters;
      3 of the 7 returned with no change in their original symptoms. Six patients from
      the study group returned. All had a definite change in their symptoms of
      photopsia or floaters. No patient in the study group who returned had old or
      persistent symptoms. Statistical analysis comparing return visits of patients
      with no change in symptoms in the two groups by Fisher's Exact Test gave a p
      value of 0.13. CONCLUSION: Patients counselled following uncomplicated PVD did
      not return to eye casualty in the absence of new symptoms. Patient counselling is
      an important part of the management of PVD because it makes patients aware of
      which symptoms are important predictors of serious vitreoretinal pathology.

PMID- 11339581
TI  - Time to treatment of uveal melanoma in the United Kingdom.
AB  - PURPOSE: To measure delay before treatment of uveal melanoma. METHODS: A
      retrospective study was carried out of patients referred for diagnosis and
      treatment of uveal melanoma at the Liverpool Ocular Oncology Centre (LOOC), a
      tertiary adult ocular oncology service. Participants were patients with uveal
      melanoma presenting to an optometrist or general practitioner in the United
      Kingdom between 1997 and 2000. Main outcome measures were delay at each stage of
      the referral process according to route of referral and tumour size. RESULTS:
      Delays greater than 2 weeks occurred (1) between presentation to the optometrist
      or general practitioner and the ophthalmologist's examination in 50% of patients;
      (2) between the ophthalmologist's examination and receipt of the referral at the
      ocular oncology centre in 34%; (3) between receipt of referral at the oncology
      centre and first assessment at that centre in 16%; and (4) between first
      assessment at the oncology centre and treatment in 8%. The waiting time for the
      ophthalmologist's examination was greater if the optometrist referred the patient
      via the general practitioner instead of directly. The median overall delays
      between presentation and treatment were 129 days for small tumours, 50 days for
      medium-sized tumours and 34 days for large tumours. CONCLUSIONS: Many patients
      with uveal melanoma experience long delays before treatment. Patients wait longer
      to see an ophthalmologist if their tumour is small or if they are referred by the
      optometrist to the general practitioner instead of directly to the
      ophthalmologist. Several patients also experience long delays after seeing the
      ophthalmologist, some having a large tumour by the time of teatment.

PMID- 11339582
TI  - Ethnic variation in fluorescein angiography induced nausea and vomiting.
AB  - PURPOSE: A prospective survey was undertaken to investigate ethnic variations in
      the frequency of nausea and vomiting after fundus fluorescein angiography (FFA).
      METHOD: Between May and September 1998, 197 adult patients were recruited to the
      study. A questionnaire containing closed-ended questions was completed by nurses
      after each FFA and a questionnaire was given to patients to complete 5 hours
      after the procedure at home. Patients' anxiety level was measured before FFA
      using a 5-item ordinal response scale. RESULTS: Results indicate that patients
      from black, Asian, Chino-Asian and mixed ethnic origins are significantly more
      likely to vomit and feel nauseous immediately after the administration of
      fluorescein dye. Patients with a history of nausea after FFA are significantly
      more likely to feel nauseous again after repeat FFA. CONCLUSION: Ethnic origin
      and a previous history of nausea and vomiting appear to be important factors in
      FFA-induced nausea and vomiting. The results of this study have led the
      investigators to develop a protocol for the prophylactic treatment of nausea and
      vomiting following FFA.

PMID- 11339583
TI  - Selective reduction of the S-cone component of the electroretinogram in Posner
      Schlossman syndrome.
AB  - PURPOSE: The changes in short wavelength sensitive (S-) cone electroretinograms
      (ERGs) to ganzfeldt flash stimuli were examined in patients with Posner
      Schlossman syndrome to study the differences in S-cone action in both the acute
      attack phase and the remission phase. METHODS: Ganzfeldt colour flashes under
      bright white background illumination were used to elicit short wavelength (S-),
      and mixed long- (L) and middle- (M) wavelength sensitive cone ERGs. Three
      subjects with unilateral Posner-Schlossman syndrome and 18 age-matched normal
      controls were compared. To compare the media opacity we obtained the L,M-cone
      balance, namely, the log density units of the neutral density filter required to
      produce the L,M-cone b-wave elicited with red stimuli which is identical to those
      with blue stimuli. RESULTS: Selective reduction of the S-cone ERG b-wave in acute
      attacks of Posner-Schlossman syndrome was found. Two of three cases showed the
      recovery of the S-cone b-wave with a decrease in the intraocular pressure. With
      regard to the implicit time, significant delay of the S-cone b-wave could not be
      detected in all subjects. CONCLUSION: Selective reduction of the S-cone component
      of the ERG during raised intraocular pressure was found. The S-cone pathway is
      thought to be more vulnerable to damage than the L,M-cone systems following
      elevations of intraocular pressure.

PMID- 11339584
TI  - Scleral contact lenses for overnight wear in the management of ocular surface
      disorders.
AB  - PURPOSE: To describe the use of overnight wear scleral contact lenses (Scl CLs).
      The authors describe 7 patients using this modality of contact lens wear. Most of
      the lenses were made from highly gas-permeable materials, but a long-standing
      case is also reported when the lenses were made from PMMA, which is impermeable
      to gases. BACKGROUND: There is a range of therapeutic indications for the use of
      Scl CLs. The development of rigid gas-permeable (RGP) materials has widened this
      range. CASE REPORTS: Seven case reports are presented which describe patients in
      whom severe ocular surface disease has been managed with overnight-wear Scl CLs.
      The indications were: corneal exposure, post-radiotherapy complications, Stevens
      Johnson disease, recurrent erosion and congenital or post-surgical lid defects.
      CONCLUSION: Scl CLs provide a therapeutic option for a range of complicated
      corneal and ocular surface conditions for which the treatment by other methods is
      either unsuitable or less effective. They have several advantages over silicone
      rubber and hydrogel lenses. The relative ease of handling for some patients
      allows removal for cleaning, their rigidity gives stability and a high degree of
      protection to the ocular surface, and the presence of a pre-corneal fluid
      reservoir optically neutralises an irregular corneal surface. Highly oxygen
      permeable materials enable consideration of overnight wear in appropriate
      circumstances.

PMID- 11339585
TI  - Necrotising orbital cellulitis.
AB  - PURPOSE: To report 2 cases of severe necrotising orbital cellulitis which
      illustrate the need for aggressive surgical management to prevent blindness.
      METHODS: The case records of 2 patients with necrotising orbital cellulitis were
      reviewed. RESULTS: Both patients had orbital cellulitis associated with
      sinusitis. Each case was characterised by the rapid development of severe
      systemic toxicity, extensive soft tissue necrosis and abscess formation. One
      patient developed panophthalmitis and the eye had to be eviscerated. The other
      patient underwent repeated surgical drainage of multiple orbital abscesses. This
      led to resolution of the infection and preservation of vision. CONCLUSIONS:
      Atypical rapidly progressive necrotising orbital cellulitis may occasionally be
      encountered. In such cases, aggressive surgical drainage of orbital abscesses is
      crucial to prevent blindness and death.

PMID- 11339586
TI  - Mersilene mesh sling as an alternative to autogenous fascia lata in the
      management of ptosis.
AB  - PURPOSE: To evaluate the use of Mersilene mesh as a brow suspensory material and
      to compare it clinically against autogenous fascia lata. METHODS: A prospective
      study was carried out in which 80 eyes of 56 patients with ptosis and absent,
      poor or abnormal levator function were operated on. The patients were divided
      into two groups. In 46 eyes of 32 patients Mersilene mesh was used and in 34 eyes
      of 24 patients autogenous fascia lata was used. The results were recorded and
      analysed. RESULTS: The age range for the Mersilene group was larger than for the
      fascia lata group and female patients preferred Mersilene over fascia lata. The
      improvement in lid height was significant in all cases in both groups. The
      complication rates were similar in the two groups and the mesh was well tolerated
      by the patients. No cases of infection, sling exposure or extrusion occurred with
      the use of Mersilene. Lid lag and lagophthalmos occurred as a complication of the
      procedure itself and not the type of the sling material. The mean follow-up
      period was 33.8 months for both groups. CONCLUSION: We believe that Mersilene
      mesh is an effective alternative to autogenous fascia lata when the use of fascia
      lata is felt inappropriate.

PMID- 11339588
TI  - Heroin withdrawal as a possible cause of acute concomitant esotropia in adults.
AB  - PURPOSE: To report the possible effects of heroin withdrawal on binocular vision.
      METHODS: A case series of patients is presented in whom esotropia developed on
      cessation of heroin use. RESULTS: In each case the esotropia was concomitant and
      prismatic correction restored binocular single vision. Intermittent spontaneous
      control occurred in one patient, the deviation resolved in one and one patient
      was lost to follow-up. CONCLUSIONS: Heroin withdrawal should be considered as a
      cause of acute concomitant esotropia. However, an accurate history of other
      medication is needed to ensure that this is not the cause of decompensation.

PMID- 11339587
TI  - Mitochondrial DNA analysis in the Turkish Leber's hereditary optic neuropathy
      population.
AB  - PURPOSE: To define the prevalence of a panel of mitochondrial DNA (mtDNA)
      mutations associated with Leber's hereditary optic neuropathy (LHON) in the
      Turkish LHON population. LHON-associated mtDNA mutations have been found in LHON
      patients from around the world, but the Turkish LHON population has not been
      studied. METHODS: Thirty-two Turkish patients were defined clinically as having
      LHON on the basis of painless, subacute, bilateral optic neuropathy and the
      exclusion of other causes of subacute optic neuropathy. mtDNA was extracted from
      blood of the 32 probands and assayed for a panel of primary and secondary LHON
      associated mtDNA mutations by polymerase chain reaction (PCR)-based methods. We
      studied three well-known LHON-associated primary mutations (at nucleotide
      positions 11778, 3460 and 14484) and one common secondary mutation (at nucleotide
      15257) in all 32 probands. In addition to these mutations, 18 of the 32 probands
      were tested for the Complex IV, COX III gene, LHON associated 9804 and 9438
      mutations and secondary LHON mutations at nucleotide positions 3394, 4160, 4216,
      4917, 5244, 7444, 7706, 13708, 13730 and 15812. RESULTS: Among the 32 probands
      tested for four common LHON mutations, 3 carried the 14484 mutation, 1 carried
      the 11778 mutation, 1 carried the 3460 mutation and 1 carried the 15257 mutation.
      Among the 18 LHON patients who tested for additional mutations, 1 proband
      harboured the 9804 mutation and 4 carried the secondary mutations at nucleotide
      positions 4216, 4917 and 13708. CONCLUSION: The results of mtDNA analysis of the
      Turkish LHON patients appear to be different from those of previous reports.

PMID- 11339589
TI  - Movement detection threshold and ocular hypertension.
AB  - PURPOSE: To determine whether patients with ocular hypertension (OH) have
      elevated oscillatory movement displacement thresholds (OMDT) indicative of early
      neural damage. METHODS: Evidence of early neural loss was sought using OMDT. The
      OMDT of 29 normotensive individuals were compared with those obtained from 44
      untreated age-matched OH eyes (20 male, 24 female). RESULTS: A mean OMDT at 15
      sec arc at 40 years of age was obtained in normotensive individuals, the age
      trend increasing by about 4 sec arc per decade. About one-third of all ocular
      hypertensives (13 cases; 6 male, 7 female), who were dismissed without treatment,
      exhibited abnormal OMDT. An equal proportion of abnormal thresholds were observed
      in individuals in each decade, although the age trend diverges from that
      established for normotensives with increasing age. Mean OMDT for ocular
      hypertensives (37.1 sec arc) were significantly different (t = 2.7, p < 0.007)
      from the mean obtained from normotensives (22.2 sec arc). CONCLUSION: The results
      emphasise the need for more rigorous differentiation of OH using psychophysical
      techniques indicating early neural damage.

PMID- 11339590
TI  - Non-penetrating deep sclerectomy versus trabeculectomy in primary open-angle
      glaucoma surgery.
AB  - PURPOSE: To compare the intraocular pressure lowering effect and the frequency of
      post-operative complications in two of the most used filtration surgery
      techniques: trabeculectomy and non-penetrating deep sclerectomy (NPDS) without
      collagen implants. METHODS: Thirty-four eyes of 17 patients with medically
      uncontrolled symmetrical primary open-angle glaucoma were included in the study.
      One randomly selected eye per patient had either trabeculectomy or NPDS without
      collagen implants as the first surgical procedure. The other eye underwent the
      second filtration surgery technique less than 6 weeks later. Post-operatively,
      the intraocular pressure (IOP) diurnal curves were determined at 1, 2, 3, 6, 12
      and 18 months. The intergroup differences in IOP lowering effect were determined
      in an analysis of covariance (ANCOVA), with pre-operative IOP as a changing
      covariate. Kaplan-Meier survival curves were drawn for IOP, and intercurve
      analysis was performed. Comparisons of the number of post-operative
      antiglaucomatous medications, as well as of the complication rate, were done by 2
      x 2 frequency tables. A p value of less than 0.05 was considered statistically
      significant. RESULTS: There were statistically significant differences in post
      operative IOP level between the two groups at 1, 2, 3, 6, 12 and 18 months, with
      a lower level in the trabeculectomy group. Using the Kaplan Meier cumulative
      survival curve, the trabeculectomy patients had a better complete success rate
      than the NPDS patients at 18 months post-operatively. There were statistically
      significantly fewer complications in the NPDS group. CONCLUSION: Trabeculectomy
      lowers the IOP more than the NPDS technique. However, the complication rate seems
      to be lower in NPDS.

PMID- 11339591
TI  - Prospective evaluation of a plate haptic toric intraocular lens.
AB  - PURPOSE: Standard intraocular lenses (IOL) only correct the spherical component
      of aphakic refractive error. This study describes clinical experience with a
      foldable, injectable, toric IOL. METHODS: Keratometric, refractive and visual
      data were collected on patients listed for cataract surgery. Toric IOLs were
      offered where keratometric cylinder was greater than 1.5 dioptres. Small-incision
      phacoemulsification surgery was performed and the IOL implanted with its long
      axis along the steep corneal axis. Post-operative refractive data were compared
      with pre-operative and expected refraction using vector analysis software.
      RESULTS: Results of 22 eyes of 16 consecutive patients implanted with toric IOLs
      are reported. Two IOLs rotated more than 30 degrees in the first 24 h and were re
      dialled surgically. Two further IOLs (9%) rotated more than 30 degrees during
      follow-up. In 21 of 22 eyes (95%) the refractive astigmatism was reduced, with a
      mean 73% of planned correction (vector analysis) achieved. CONCLUSIONS: The toric
      IOL is a useful surgical tool to reduce the refractive effects of pre-existing
      corneal astigmatism. Design modification to prevent IOL rotation would make
      results more predictable.

PMID- 11339592
TI  - Presumed interference colours at the level of the human anterior lens capsule.
AB  - PURPOSE: To assess the incidence and related factors of the presumed interference
      colour phenomenon at the anterior lens capsule. METHODS: In 274 eyes of 137
      normal subjects, ranging in age from 4 to 83 years old (50.1 +/- 24.9 years, mean
      +/- standard deviation), the anterior lens capsule was observed with slit-lamp
      microscopy under specular conditions to assess the presence and degree of
      presumed interference colours. RESULTS: The colouring phenomenon, which was
      thought to be relevant to the interference phenomenon induced at the level of the
      anterior lens capsule, was found in 67.5% of eyes. Typically, there was a colour
      spectrum with a greenish tint in the central area and a reddish tint at the
      periphery, which coincided with the area of capsular shagreen. Multiple
      regression analysis revealed a signigificant positive correlation between the
      degree of the interference colour phenomenon and the age of the subjects (r =
      0.45, p < 0.0001, R2 = 0.713). CONCLUSION: Presumed interference colours are
      frequently seen at the human anterior lens capsule. Interference colours and
      capsular shagreen seem to reflect age-related changes in the lens.

PMID- 11339593
TI  - Short-term mortality among middle-aged cataract surgery patients.
AB  - PURPOSE: To investigate the short-term mortality of middle-aged patients
      undergoing cataract surgery in the United Kingdom (UK), to compare this with the
      expected mortality for the UK population of similar age and to try to identify at
      risk groups. METHODS: In a retrospective study, the 5-10 year mortality of all
      middle-aged patients undergoing cataract surgery between 1989 and 1993 was
      determined. Expected mortality was calculated from UK Interim Life Tables for
      1991. Cox's regression analysis was performed using age, sex and self-assigned
      ethnic group as variables. RESULTS: From the 709 patients in the study group,
      there were 86 deaths. This is significantly greater than expected (p < 0.01).
      Ethnic minority status (hazard ratio = 1.72, confidence interval = 1.12-2.64) and
      male sex (HR = 1.68, CI = 1.08-2.63) were found to be significantly associated
      with early mortality (p < 0.05). CONCLUSIONS: This study suggests that, for some
      middle-aged patients, cataract is associated with a reduced life expectancy and
      may be a feature of premature ageing, reflecting systemic ill-health. Screening
      these and younger patients for systemic disease when they present with cataract
      provides the best opportunity to affect this increased mortality. The findings of
      this study are particularly relevant for patients from ethnic minority groups.

PMID- 11339594
TI  - Effects of epidermal growth factor in artificial tear on vitamin C levels of
      corneal wounded eye tissues.
AB  - PURPOSE: To investigate the effect of artificial tear (AT) solution and epidermal
      growth factor (EGF) treatment on the cornea and aqueous humour ascorbic acid (AA)
      levels of full-thickness corneal wounded eyes. METHODS: The effect of EGF on the
      AA levels of aqueous humour and corneal wound tissue was determined in full
      thickness corneal wounded rabbit eyes on the seventh post-operative day. There
      were three groups: untreated controls, AT-treated controls and an EGF+AT-treated
      experimental group (n = 6 in each group). Corneal wounded eyes were topically
      treated with 5 microl AT or 5 microl EGF in AT (1 mg/l EGF in AT prepaaration
      which contained 3.0% carbopol 940) twice daily for 6 days after operation. The
      wound strengths were also measured on the seventh post-operative day as a measure
      of wound healing. Statistical analysis was carried out using the Mann-Whitney U
      test by Statview program. RESULTS: The wound strengths of corneas, and AA levels
      of wound tissues and aqueous humour, increased significantly following AT and EGF
      treatment (p < 0.05). CONCLUSION: In the corneal wounded eye, aqueous humour
      serves as a source of vitamin C and there may be a relation between EGF treatment
      in AT and AA levels of corneal wounded eye tissues.

PMID- 11339595
TI  - Expression of CD23/CD21 and CD40/CD40 ligand in vernal keratoconjunctivitis.
AB  - PURPOSE: The overproduction of immunoglobulin E (IgE) antibodies is associated
      with vernal keratoconjunctivitis (VKC). CD23/CD21 and CD40/CD40 ligand (CD40L)
      interactions have been proposed to be involved in the regulation of IgE
      synthesis. The purpose of the present study was to investigate the presence and
      distribution of CD23, CD21, CD40 and CD40L in the conjunctiva from patients with
      active VKC. METHODS: Conjunctival biopsy specimens from 8 subjects with active
      VKC and 6 control subjects were studied. We used immunohistochemical techniques
      and a panel of monoclonal antibodies (mAbs) directed against CD23, CD21, CD40 and
      CD40L. In addition, a panel of mAbs were used to characterise the composition of
      the inflammatory infiltrate. RESULTS: In the normal conjunctiva, basal epithelial
      cells and vascular endothelial cells in the upper substantia propria showed a
      constitutive very weak immunoreactivity for CD40. The immunoreactivity for CD23,
      CD21 and CD40L was absent. In VKC specimens, the stromal inflammatory infiltrate
      was orgnanised as a diffuse infiltrate and as small lymphoid follicles consisting
      of CD20+ B lymphocytes intermingled with smaller numbers of CD3+ T lymphocytes,
      and CD68+ monocytes/macrophages. Lymphocytes in the centre of the lymphoid
      follicles showed CD23 and CD21 immunoreactivity. CD40 immunoreactivity in
      epithelial cells and vascular endothelial cells was stronger in VKC specimens
      than in control eyes. Furthermore, the majority of mononuclear cells, including T
      and B lymphocytes, showed immunoreactivity for CD40. CD40L immunoreactivity was
      not detected. CONCLUSION: B lymphocytes in the lymphoid follicles expressing
      CD23, CD21 and CD40 are activated and might be precursors of IgE-producing B
      cells. These results suggest that the conjunctiva might contribute to IgE
      synthesis.

PMID- 11339596
TI  - Branch retinal artery obstruction with simultaneous central retinal vein
      occlusion.

PMID- 11339597
TI  - Vogt-Koyanagi-Harada syndrome presenting as a severe systemic illness.

PMID- 11339598
TI  - Aggressive retinal vasculitis in polyarteritis nodosa.

PMID- 11339599
TI  - Posterior scleritis mimicking birdshot retinochoroidopathy.

PMID- 11339600
TI  - Siegrist's streaks: a rare manifestation of hypertensive choroidopathy.

PMID- 11339601
TI  - Surgical exploration minimised by ultrasound biomicroscopy localisation of
      intraocular foreign body.

PMID- 11339602
TI  - Haemorrhagic conjunctivitis as an initial manifestation of systemic meningococcal
      disease.

PMID- 11339603
TI  - Pericardial patch melting following glaucoma implant insertion.

PMID- 11339604
TI  - Bilateral endogenous Candida endophthalmitis as the presenting manifestation of
      diabetes mellitus.

PMID- 11339605
TI  - Spontaneous hyphaema secondary to a vascularised fragment of persistent pupillary
      membrane.

PMID- 11339606
TI  - Blood-stained keratic precipitates: presenting feature of sarcoidosis with
      thrombocytopenia.

PMID- 11339607
TI  - The use of supplementary blue light during Perkins applanation tonometry in
      theatre.

PMID- 11339608
TI  - The use of the phacoemulsification keratome in dacryocystorhinostomy.

PMID- 11339609
TI  - An unusual case of cavernous sinus syndrome.

PMID- 11339610
TI  - Spontaneous iris sphincter ruptures due to lens-iris diaphragm retropulsion
      syndrome during phacoemulsification.

PMID- 11339611
TI  - Retinal toxicity due to Efavirenz.

PMID- 11339612
TI  - Angle closure risk from proprietary medicines.

PMID- 11339613
TI  - Positive temporal artery biopsy in a patient on therapeutic doses of steroids for
      six years.

PMID- 11339614
TI  - Sphenoid dysplasia and temporal lobe prolapse in neurofibromatosis type 1.

PMID- 11339615
TI  - Apocrine sweat gland carcinoma.

PMID- 11339616
TI  - Double bitemporal hemianopia.

PMID- 11339617
TI  - The eyelid is a site of occurrence of desmoplastic trichilemmoma.

PMID- 11339618
TI  - Assessment of prenatal smoke exposure by determining nicotine and its metabolites
      in maternal and neonatal urine.
AB  - Urine specimens were collected from 75 pregnant women before childbirth and from
      their newborns within 48 postnatal hours. A high-performance liquid
      chromatography (HPLC) method was used to determine urinary nicotine and its
      metabolites, cotinine and trans-3'-hydroxycotinine (OH-cotinine) to objectivise
      prenatal smoke exposure. Using the sum of nicotine metabolites as a marker, 34
      women were classed as not exposed to smoke ( < 15 nmol/l), 18 as passive smokers
      (15-400 nmol/l), and 23 as active smokers ( > 400 nmol/1). The newborns of active
      smokers exhibited significantly (P < 0.001) higher nicotine metabolite
      concentrations than did those of either non-exposed women or passive smokers. A
      close correlation was found to exist between maternal and neonatal nicotine and
      cotinine concentrations (r=0.8968 and r=0.9205, respectively). For OH-cotinine,
      this correlation was particularly close when maternal, but not neonatal, OH -
      cotinine was adjusted to creatinine (r=0.9792). The neonatal/maternal urine
      concentration ratios for cotinine and OH-cotinine were noted to not significantly
      depend on the time of postpartal urine collection. Within the first two postnatal
      days, the extent of current prenatal smoke exposure attributable to active
      smoking of the mother was best reflected by the urinary concentrations of
      cotinine plus OH-cotinine without adjustment to creatinine.

PMID- 11339619
TI  - Aggressive atropinisation and continuous pralidoxime (2-PAM) infusion in patients
      with severe organophosphate poisoning: experience of a northwest Indian hospital.
AB  - OBJECTIVE: The aim of the study was to find whether continuous pralidoxime (2
      PAM) infusion along with aggressive atropinisation improves the outcome in
      patients with severe organophosphate poisoning who require assisted ventilation.
      METHODS: Sixteen patients admitted to the respiratory intensive care unit (RICU)
      with severe organophosphate poisoning and requiring assisted ventilation were
      included in the study. The compounds involved were phorate (six), dichlorvos
      (four), oxydimeton methyl (one), monocrotophos (one), methyl parathion (one) and
      in three it was unknown. After decontamination, they were given intravenous (iv)
      bolus atropine 5 mg at onset and then 2.5 mg every 5-10 min till atropinisation
      was achieved, and then maintained either by intermittent bolus doses or by
      continuous infusion if the required dose was large. They were also given
      continuous iv infusion of 2-PAM in dose of 7.5 mg/ kg body weight/h (maximum 500
      mg/h) after an initial bolus dose of 2 g. RESULTS: The mean (+/-S.D.) dose of
      atropine was 735.02 +/- 742.98 mg (range 85-3000 mg) with maximum dose on day 1.
      The mean (+/-S.D) duration of 2-PAM infusion was 96.4+/-49.4 h (range 10-216 h).
      The mean (+/-S.D) duration of mechanical ventilation (MV) was 131.5 +/- 95.65 h
      (range 4-336 h). Fourteen patients could be successfully extubated and two died
      of bronchopneumonia and sepsis (mortality 12.5%). CONCLUSION: Continuous 2-PAM
      infusion along with aggressive atropinisation after initial decontamination
      improved the outcome but not the duration of MV in severely intoxicated patients
      with organophosphate compounds who required assisted ventilation in this case
      series.

PMID- 11339620
TI  - Near-fatal gamma-butyrolactone intoxication--first report in the UK.
AB  - Gamma-hydroxybutyrate (GHB) is a compound used in the treatment of alcohol
      withdrawal, narcolepsy, and for induction of anaesthesia. It is also contained in
      many products illegally marketed as "dietary supplements" and is increasingly
      being recognised as a potential drug of abuse. We report the case of a 44-year
      old man who suffered coma and life-threatening respiratory depression following
      an accidental overdose of the GHB prodrug, gamma-butyrolactone (GBL), contained
      in a "health drink". He made a full recovery following appropriate supportive
      treatment. GHB toxicity should be included in the differential diagnosis of
      patients with altered mental state, particularly where there is a history of
      recreational drug abuse.

PMID- 11339621
TI  - The protective effect of taurine against thioacetamide hepatotoxicity of rats.
AB  - Thioacetamide (TAA) administration (three consecutive intraperitoneal injections
      of 400 mg/kg at 24-h interval) to rats resulted in hepatic injury as assessed by
      the measurement of serum transaminase activities and histopathological findings.
      This treatment caused an increase in the levels of malondialdehyde (MDA), diene
      conjugates (DCs) and glutathione (GSH) and the activity of superoxide dismutase
      SOD ), and a decrease in the levels of vitamins E and C and the activity of
      glutathione peroxidase (GSH-Px) in the liver of rats. Taurine administration (400
      mg/kg, i.p., every 12 h and started 24 h prior to the first TAA injection) was
      found to decrease serum transaminase activities and hepatic lipid peroxidation
      without any significant change in hepatic antioxidant system. Histopathological
      findings also suggested that taurine has ameliorated effect on TAA-induced
      hepatic necrosis. These results indicate that taurine treatment, together with
      TAA administration, diminished the severity of the liver injury by decreasing
      oxidative stress due to its possible scavenger effect.

PMID- 11339622
TI  - Protection by selenium of lead-acetate-induced alterations on rat submandibular
      gland function.
AB  - Pure submandibular saliva was collected intraorally by micro polyethylene
      cannulation of anaesthetized rats using pilocarpine as a secretagogue. Twenty
      four days treatment with lead acetate 0.05% in drinking water altered salivary
      function. Except for flow rate that was (P<0.01) increased by lead acetate, the
      reminder of parameters, concentrations of total protein and calcium and the
      activity of N-acetyl-beta-D-glucosaminidase (NAG) in submandibular secretions
      were decreased significantly (P<0.01) by lead acetate. Selenium (2.5 mg l(-1)) in
      drinking water for 24 days did not induce any significant change in saliva
      secretory function. Pretreatment by selenium, prevented the lead acetate-induced
      decrease of NAG activity and concentrations of calcium and protein (P<0.01). The
      increased flow rate by lead acetate was also affected by selenium pretreatment
      and reached the level of control. It is concluded that selenium can protect rat
      submandibular gland function from lead-acetate-induced adverse effects.
      Properties of selenium as an antioxidant, free radical scavenger and maintenance
      of cell membrane integrity may be possible mechanisms of its protective effects.

PMID- 11339623
TI  - Aspirin impairs antioxidant system and causes peroxidation in human erythrocytes
      and guinea pig myocardial tissue.
AB  - This study aims to investigate possible effects of aspirin treatment on cellular
      oxidant/antioxidant system. In the first part of the study, 15 guinea pigs were
      given aspirin at three different doses (2200, 440 and 10 mg/kg/day) for 30 days
      and five were fed on the same diet without aspirin. After a month, animals were
      killed and their hearts were removed for use in analyses. In the other part,
      after fasting blood samples were obtained from 11 volunteer subjects, they were
      given aspirin (approximately 10 mg/kg/day) for 30 days and second blood samples
      were obtained after 1 month. Five volunteer subjects also participated as placebo
      control. Oxidant/antioxidant parameters, namely superoxide dismutase (SOD),
      glutathione peroxidase (GSH-Px), catalase (CAT), malondialdehyde (MDA),
      nonenzymatic superoxide scavenger activity (NSSA), susceptibility to oxidation
      (SO) and antioxidant potential (AOP) values, were assayed in the samples.
      Antioxidant system was found to be impaired in the heart tissue from guinea pigs
      and in the erythrocytes from volunteer subjects. AOP and NSSA values were lower
      and MDA higher after aspirin treatment in both heart tissues and erythrocytes. In
      guinea pig heart tissue, SO was lower, but GSH-Px and CAT were unchanged after
      aspirin treatment. In human erythrocytes, SO was unchanged, but GSH-Px and CAT
      activities were increased after aspirin treatment. Changes in guinea pig heart
      tissues from animals treated with higher aspirin doses were more drastic relative
      to those of human erythrocytes, but no meaningful differences were observed
      between analysis parameters of control and lower-dose (10 mg/kg/day) aspirin
      treated animals. Our results suggest that high-dose aspirin exerts significant
      toxicity to guinea pig myocardium and normal dose aspirin may cause peroxidation
      in the human erythrocytes due to its oxidant potential. We suppose that
      antioxidant supplementation may be beneficial for the people using aspirin for
      longer periods in order to prevent peroxidation damages.

PMID- 11339624
TI  - Stimulation of myelopoiesis in Listeria monocytogenes-infected mice by an
      aggregated polymer isolated from Aspergillus oryzae.
AB  - In this work, we investigated the effects of the proteic aggregated polymer of
      magnesium ammonium phospholinoleate-palmitoleate anhydride (MAPA) isolated from
      Aspergillus oryzae on the growth and differentiation of bone marrow granulocyte
      macrophage progenitor cells (CFU-GM) in Listeriamonocytogenes-infected mice. A
      significant reduction in the CFU-GM number was observed in the initial phase of
      infection with a sublethal dose of Listeria. Treatment of mice with 0.5, 2.0 and
      5.0 mg/kg MAPA for 7 days prior to infection significantly stimulated
      myelopoiesis in a dose-dependent manner. Moreover, treatment with 0.5 and 5.0
      mg/kg MAPA resulted in 30% and 40% cures of mice lethally infected with Listeria,
      respectively. MAPA added directly to the culture dishes hardly affected colony
      formation by bone marrow cells, suggesting an indirect effect ofthis compound on
      myelopoiesis in vivo. In summary, the data show that MAPA can modulate the CFU-GM
      generation and antibacterial resistance in listeriosis. As the ability of
      hematopoietic tissues to produce phagocytes is of particular significance to
      mediate resistance to Listeria, the promotion of bone marrow CFU-GM by MAPA may
      contribute to a rapid restoration of phagocyte numbers in infected sites, thus
      mitigating the course of infection.

PMID- 11339625
TI  - Silica-induced cytokine release from A549 cells: importance of surface area
      versus size.
AB  - Physical and chemical properties such as structure, composition and surface
      reactivity determine the biological activity of mineral particles. Long-term
      exposure to crystalline silica is known to cause persistent pulmonary
      inflammation leading to adverse health effects. There is less information about
      the potential health effects of amorphous (noncrystalline) silica. In this study,
      the inflammatory and cytotoxic potency of crystalline and amorphous silica in
      relation to particle size and surface area was assessed. Human epithelial lung
      cells (A549) were exposed to different size fractions of quartz ( aerodynamic
      diameter 0.5, 2 and 10 microm) and amorphous silica (diameter 0.3 microm). All
      particles induced increased release of the proinflammatory cytokines interleukin
      (IL)-6 and IL-8. When cells were exposed to equal masses of quartz, the smallest
      size fraction was the most potent. These differences, however, disappeared when
      cytokine release was related to equal surface areas. When amorphous silica and
      quartz were compared, the amorphous silica was most potent to induce IL - 6
      regardless of how exposure was expressed, whereas the smallest size fraction of
      quartz was the most potent inducer of IL-8. Thus, the surface area seems to be
      the critical determinant when potency of different sizes of quartz is compared.

PMID- 11339626
TI  - Toxic encephalopathy associated with use of DEET insect repellents: a case
      analysis of its toxicity in children.
AB  - (1) Respiratory distress and seizures developed in an 18-month-old boy following
      brief exposure to low-strength (17.6%) N,N-diethyl-m-toluamide (DEET). A review
      of the literature revealed 17 reports of DEET-induced encephalopathy in children.
      The objective of this study was to test the hypothesis that the potential
      toxicity of DEET is high and that available repellents containing DEET,
      irrespective of their strength, are not safe when applied to children's skin. (2)
      Although this is a case report, we used the features of published reports of DEET
      induced encephalopathy in children to support the diagnosis, since the evidence
      that the child's illness was caused by DEET was circumstantial. In the following
      case analysis, clinical reports of children < 16 years old have been reviewed and
      analyzed in an effort to relate direct DEET toxicity to various clinical,
      demographic, and toxic compound exposure factors (Fisher's exacttest and logistic
      regression analysis). (3) DEET-induced encephalopathy in children (56% girls)
      followed not only ingestion or repeated and extensive application of repellents,
      but also a brief exposure to DEET (45%). Of those who reported a dermal exposure,
      33% reported an exposure to a product containing DEET < 20%. Seizures, the most
      prominent symptom (72%), were significantly more frequent when DEET solutions
      were applied to the skin (P<0.01). Mortality (16.6%) did not correlate
      significantly with the concentration of the DEET liquid used, duration of skin
      exposure, pattern of use, age, or sex. (4) Data of this case analysis suggest
      that repellents containing DEET are not safe when applied to children's skin and
      should be avoided in children. Additionally, since the potential toxicity of DEET
      is high, less toxic preparations should be probably substituted for DEET
      containing repellents, whenever possible.

PMID- 11339627
TI  - Electrochemical behavior and differential pulse polarographic determination of
      rifampicin in the pharmaceutical preparations.
AB  - Differential pulse polarographic (DPP) analytical procedure for the rifampicin
      antibiotic, which can be applied to monitor its synthetic process from the
      starting antibiotic of rifamycin B or rifamycin SV, has been developed based on
      the electrochemical reduction of an azomethine group. Rifampicin exhibited a
      cathodic peak due to the azomethine group in the side chain of 3-[(4-methyl-1
      piperazinyl)imino]methyl moiety and another cathodic peak due to the carbonyl
      group in rifamycin SV by DPP The experimental peak potential shift of an
      azomethine reduction was -73 mV/pH in the pH range between 3.0 and 7.5, agreeing
      with involvement of 4 e- and 5 H+ in its reduction. By the cyclic
      voltammetric(CV) studies, the azomethine and the carbonyl reductions in
      rifampicin were processed irreversibly on the mercury electrode. The plot of peak
      currents vs. concentrations of rifampicin ranging 1.0 x 10(-7) M tp approximately
      1.0 x 10(-5) M yielded a straight line with a correlation coefficient of 0.9996.
      The detection limit was 1.0 x 10(-8) M with a modulation amplitude of 50 mV. DPP
      has been successfully applied for the determination of rifampicin in the
      pharmaceutical preparations.

PMID- 11339628
TI  - A new antioxidant monoterpene glycoside, alpha-benzoyloxypaeoniflorin from
      Paeonia suffruticosa.
AB  - Alpha-benzoyloxypaeoniflorin (1), a new antioxidant monoterpene alpha-glycoside
      anomer was isolated from Paeonia suffruticosa along with known compounds, beta
      benzoyloxypaeoniflorin (2), paeonolide, paeoniflorin and mudanpioside H. The
      structure of 1 has been determined by comparing spectral data with those of beta
      benzoyloxypaeoniflorin (2). Compound 1 exhibited moderately potent radical
      scavenging activity on DPPH radical.

PMID- 11339629
TI  - Anticoagulant activity of sulfoalkyl derivatives of curdlan.
AB  - Curdlan is a natural beta-1,3-glucan produced by Agrobacterium biovar 1. In this
      study, the anticoagulant activity of sulfoalkyl derivatives of curdlan was
      investigated by carrying out activated partial thromboplastin time (APTT) assay
      and compared with that of o-sulfonated curdlan. Approximately 100-fold higher
      concentration of o-sulfonated curdlan than heparin was required to obtain the
      same level of the clotting time. Anticoagulant activity of curdlan derivatives
      was dependent on the degree of sulfation in prolonging the clotting time.
      However, the chain length of the substituent did not play a role in prolonging
      the clotting time. The curdlan derivatives enhanced thrombin inhibition by
      mediating through antithrombin III. The inhibition of thrombin by o-sulfonated
      curdlan was found to be approximately 10-fold weaker than that by heparin.

PMID- 11339630
TI  - Protective effects of acetylbergenin against carbon tetrachloride-induced
      hepatotoxicity in rats.
AB  - The present study was undertaken to investigate whether or not the
      hepatoprotective activity of acetylbergenin was superior to bergenin in carbon
      tetrachloride (CCl4)-intoxicated rat. Acetylbergenin was synthesized by
      acetylating bergenin, which was isolated from Mallotus japonicus. The
      hepatoprotective effects of acetylbergenin were examined against CCl4-induced
      liver damage in rats by means of serum and liver biochemical indices.
      Acetylbergenin was administered orally once daily for 7 successive days, then a
      0.5 ml/kg mixture of CCl4 in olive oil (1:1) was intraperitoneally injected at 12
      h and 36 h after the final administration of acetylbergenin. Pretreatment with
      acetylbergenin reduced the elevated serum enzymatic activities of
      alanine/aspartate aminotransferase, sorbitol dehydrogenase and gamma
      glutamyltransferase in a dose dependent fashion. Acetylbergenin also prevented
      the elevation of hepatic malondialdehyde formation and depletion of glutathione
      content dose dependently in CCl4-intoxicated rats. In addition, the decreased
      activities of glutathione S-transferase and glutathione reductase were restored
      to almost normal levels. The results of this study strongly suggest that
      acetylbergenin has potent hepatoprotective activity against CCl4-induced hepatic
      damage in rats by glutathione-mediated detoxification as well as having free
      radical scavenging activity. In addition, acetylbergenin doses of 50 mg/kg showed
      almost the same levels of hepatoprotective activity as 100 mg/kg of bergenin,
      indicating that lipophilic acetylbergenin is more active against the
      antihepatotoxic effects of CCl4 than those of the much less lipophilic bergenin.

PMID- 11339631
TI  - Toxicology of Kalopanax pictus extract and hematological effect of the isolated
      anti-rheumatoidal kalopanaxsaponin A on the Freunds complete adjuvant reagent
      treated rat.
AB  - We have reported that kalopanaxsaponin A (KPS-A) isolated from Kalopanax pictus
      have anti-rheumatoidal activity in the rat treated with Freunds complete adjuvant
      (FCA) reagent. In addition, it has been also reported that KPS-A is a potent
      antioxidant in the rheumatoidal rat. This research was undertaken to examine
      whether the saponins of KPS-A and -I could adjust the abnormal lipid metabolisms
      and hematological changes in immunological diseases. KPS-A significantly
      inhibited the increases in both triglycerides and total proteins in addition to
      the decrease in total cholesterol induced by FCA reagent treatment. KPS-A
      treatment decreased the number of leucocytes elevated by FCA reagent treatment.
      Excess dose of the methanol extract produced no severe toxicity on the body
      weight, wet organ weights and hepatic functions. Since LD50 value of K. pictus
      methanol extract was shown to be 4,033 mg/kg, it could be estimated to be a safe
      agent for anti-rheumatoidal herbal medicines.

PMID- 11339632
TI  - Quinacrine induces cytochrome c-dependent apoptotic signaling in human cervical
      carcinoma cells.
AB  - Quinacrine (QU), a phospholipase-A2 (PLA-2) inhibitor has been used clinically as
      a chemotherapeutic adjuvant. To understand the mechanisms leading to its
      chemotherapeutic effect, we have investigated QU-induced apoptotic signaling
      pathways in human cervical squamous carcinoma HeLa cells. In this study, we found
      that QU induced cytochrome c-dependent apoptotic signaling. The release of pro
      apoptotic cytochrome c was QU concentration- and time-dependent, and preceded
      activation of caspase-9 and -3. Flow cytometric FACScan analysis using
      fluorescence intensities of DiOC6 demonstrated that QU-induced cytochrome c
      release was independent of mitochondrial permeability transition (MPT), since the
      concentrations of QU that induced cytochrome c release did not alter
      mitochondrial membrane potential (delta pai(m)). Moreover, kinetic analysis of
      caspase activities showed that cytochrome c release led to the activation of
      caspase-9 and downstream death effector, caspase-3. Caspase-3 inhibitor (Ac-DEVD
      CHO) partially blocked QU-induced apoptosis, suggesting the importance of caspase
      3 in this apoptotic signaling mechanism. Supplementation with arachidonic acid
      (AA) sustained caspase-3 activation induced by QU. Using inhibitors against
      cellular arachidonate metabolism of lipooxygenase (Nordihydroxyguaiaretic Acid,
      NDGA) and cyclooxygenase (5,8,11,14-Eicosatetraynoic Acid, ETYA) demonstrated
      that QU-induced apoptotic signaling may be dependent on its role as a PLA-2
      inhibitor. Interestingly, NDGA attenuated QU-induced cytochrome c release,
      caspase activity as well as apoptotic cell death. The blockade of cytochrome c
      release by NDGA was much more effective than that attained with cyclosporin A
      (CsA), a MPT inhibitor. ETYA was not effective in blocking cytochrome c release,
      except under very high concentrations. Caspase inhibitor z-VAD blocked the
      release of cytochrome c suggesting that this signaling event is caspase
      dependent, and caspase-8 activation may be upstream of the mitochondrial events.
      In summary, we report that QU induced cytochrome c-dependent apoptotic signaling
      cascade, which may be dependent on its role as a PLA-2 inhibitor. This apoptotic
      mechanism induced by QU may contribute to its known chemotherapeutic effects.

PMID- 11339633
TI  - Differential effects of fumonisin B1 on cell death in cultured cells: the
      significance of the elevated sphinganine.
AB  - Fumonisins are specific inhibitors of ceramide synthase in sphingolipid
      metabolism. An alteration in sphingolipid metabolism as a result of fumonisin
      exposure is related to cell death (Yoo et al., 1992). The objective of this study
      was to investigate whether elevated free sphinganine levels are related to the
      sensitivity of cultured cells to fumonisin exposure. Fumonisin B1 elevated the
      intracellular free sphinganine concentraions in both LLC-PK1 and Chinese hamster
      ovary (CHO) cells. However, CHO cells are resistant to fumonisin cytotoxicity at
      50 microM, while LLC-PK1 cells are sensitive at concentrations greater than 35
      microM. The intracellular concentration of free sphinganine in LLC-PK, cells
      treated at 50 microM fumonisin B1 for 72 h was approximately 1450 pmol/mg protein
      relative to the 37 pmol observed in the control culture. Under the same
      conditions, the population of apoptotic cells in the 50 M fumonisin B1-treated
      culture was approximately 37% of the total compared to 12% in the control. The
      caspase III-like activity after 72 h in the 50 microM fumonisin B1-exposed
      culture increased to approximately 50 pmol/mg protein/hr compared to 6 pmol/mg
      protein/hr in the control. L-cycloserine, a serine palmitoyltransferase
      inhibitor, reduced the fumonisin B1-stimulated caspase III-like activity down to
      the control level. Under the same culture conditions, the intracellular
      concentration of free sphinganine after L-cycloserine plus fumonisin B1 treatment
      was 140 pmol/mg protein compared to 1450 pmol/mg protein in fumonisin B1 alone.
      The intracellular concentration of free sphinganine in CHO cells treated with 50
      microM fumonisin B1 for 72 h was approximately 460 pmol/mg protein, indicating
      that the mass amount of elevated free sphinganine in the CHO cells was about 32%
      of that in LLC-PK1 cells. Adding exogenous sphinganine to the CHO cells along
      with 50 microM fumonisin B1 treatment for 72 h caused both necrosis and
      apoptosis. In conclusion, the elevated endogenous sphinganine acts as a
      contributing factor to the fumonisin-induced cell death.

PMID- 11339634
TI  - Sphingolipid metabolic changes during chiral C2-ceramides induced apoptosis in
      human leukemia cells.
AB  - N-acetylsphingosine (C2-ceramide) is a synthetic water-soluble ceramide mimicking
      the activity of natural ceramides. By fixing chiral conformation on carbon
      numbers 2 and 3 in the ceramide structure, four chiral C2-ceramides naming d
      erythro-, l-erythro-, d-threo- and l-threo C2-ceramide were synthesized. We have
      investigated the chiral effects of these C2-ceramides on the sphingolipid
      metabolism, particularly on both the sphingolipid biosynthetic pathway and on the
      degradation pathway. In both HL-60 and U937 cells, the chiral C2-ceramide (10
      microM) showed sphingosine accumulation monitored fluoromatrically by a high
      performance liquid chromatographic separation of the sphingoid bases. Most
      importantly, in HL-60 cells, l-erythro C2-ceramide induced a 50 fold increase in
      sphingosine as compared to the control, while l-threo C2-ceramide exhibited a
      minimal 7-fold increase. In contrast, sphinganine, another sphingoid base, showed
      less accumulation by any chiral C2-ceramide tested under the same conditions.
      These results suggested that chiral C2-ceramide primarily acts on the
      sphingolipid degradation pathway rather than on the sphingolipid biosynthetic
      route. The strong G0/G1 phase arrest in the cell cycle by treatment of l-erythro
      C2-ceramide indicates that the blockade of the sphingolipid degradation pathway
      might be concomitantly involved in the dysfunction of the cell cycle. On the
      other hand, the fact that all chiral C2-ceramides tested failed to inhibit the
      activity of sphingosine kinase acting on the removal of sphingosine by producing
      sphingosine-l-phosphate demonstrates that chiral C2- ceramides may increase
      sphingosine by activating various ceramidases by which natural ceramides are
      divided into sphingosine and free fatty acids. However, the precise steps
      involved in this interaction are still unknown.

PMID- 11339635
TI  - Inhibition of heat-induced denaturation of albumin by nonsteroidal
      antiinflammatory drugs (NSAIDs): pharmacological implications.
AB  - The activity of nonsteroidal antiinflammatory drugs (NSAIDs) in rheumatoid
      arthritis is not only due to the inhibition of the production of prostaglandins,
      which can even have beneficial immunosuppressive effects in chronic inflammatory
      processes. Since we speculated that these drugs could also act by protecting
      endogenous proteins against denaturation, we evaluated their effect on heat
      induced denaturation human serum albumin (HSA) in comparison with several fatty
      acids which are known to be potent stabilizers of this protein. By the Mizushimas
      assay and a recently developed HPLC assay, we observed that NSAIDs were slightly
      less active [EC50 to approximately 10(-5)-10(-4) M] than FA and that the HPLC
      method was less sensitive but more selective than the turbidimetric assay, i.e.
      it was capable of distinguishing true antiaggregant agents like FA and NSAIDs
      from substances capable of inhibiting the precipitation of denatured protein
      aggregates. In conclusion, this survey could be useful for the development of
      more effective agents in protein condensation diseases like rheumatic disorders,
      cataract and Alzheimers disease.

PMID- 11339636
TI  - Influence of temperature and pH on the stability of dimethoxy biphenyl
      monocarboxylate HCl solutions.
AB  - The accelerated stability of dimethoxy biphenyl monocarboxylate x HCl (DDB-S) was
      investigated in 6 mg/mL water solution in the pH ranging 2-10 and the temperature
      of 45-85 degrees C. The observed rate of degradation followed first-order
      kinetics. The energy of activation for DDB-S degradation was calculated to be
      14.1 and 16.5 Kcal/mole at pH 5 and in distilled water, respectively. The
      degradation rate constant (K(25 degrees C)) obtained by trending line analysis of
      Arrhenius plots for DDB-S was 5.3 x 10(-6) h(-1). The times to degrade 10% (t10)
      and 50% (t50) at 25 degrees C were 829 and 5,416 days, respectively. DDB-S
      exhibited the fastest degradation at pH 10 and the slowest rate at pH 5. In
      addition, at 65 degrees C, degradation rate constants of DDB-S were 0.066, 0.059,
      5.460, 32.171, and 1.41 x 10(6) h(-1) at pH 2, 5, 8, 10 and in distilled water,
      respectively. These observations indicated that the rate-pH profile of DDB-S
      showed general acid-base catalysis reaction in the range of pH 2-10.

PMID- 11339637
TI  - Inhibitory effect of fangchinoline on excitatory amino acids-induced
      neurotoxicity in cultured rat cerebellar granule cells.
AB  - Glutamate receptors-mediated excitotoxicity is believed to play a role in the
      pathophysiology of neurodegenerative diseases. The present study was performed to
      evaluate the inhibitory effect of fangchinoline, a bis-benzylisoquinoline
      alkaloid, which has a characteristic as a Ca2+ channel blocker, on excitatory
      amino acids (EAAs)-induced neurotoxicity in cultured rat cerebellar granule
      neuron. Fangchinoline (1 and 5 microM) inhibited glutamate (1 mM), N-methyl-D
      aspartate (NMDA; 1 mM) and kainate (100 microM)-induced neuronal cell death which
      was measured by trypan blue exclusion test. Fangchinoline (1 and 5 microM)
      inhibited glutamate release into medium induced by NMDA (1 mM) and kainate (100
      microM), which was measured by HPLC. And fangchinoline (5 microM) inhibited
      glutamate (1 mM)-induced elevation of intracellular calcium concentration. These
      results suggest that inhibition of Ca2+ influx by fangchinoline may contribute to
      the beneficial effects on neurodegenerative effect of glutamate in
      pathophysiological conditions.

PMID- 11339638
TI  - Synthesis and in vitro antibacterial activity of cephalosporins with a pyridinium
      substituent carrying an isoxazole moiety at the C-3 position.
AB  - Several quaternary pyridinium cephalosporin analogues were prepared and evaluated
      in vitro for antibacterial activity against selected gram-positive and gram
      negative organisms. Most of the synthesized analogues were either as effective or
      less effective against the tested bacterial organisms than the reference
      compounds, Cefpirome and Ceftazidime.

PMID- 11339639
TI  - Synthesis and antiviral activity of fluoro-substituted apio dideoxynucleosides.
AB  - Novel fluoro-substituted apio dideoxynucleosides ((+/-)-3a and (+/-)-3b) were
      efficiently synthesized starting from 1,3-dihydroxyacetone via Horner-Emmons
      olefination as a key step. Cyclization of fluoro ester (+/-)-6 under acidic
      conditions to the fluorolactone was smoothly proceeded in favor of trans
      fluorolactone due to the favorable transition state with equatorial hydroxymethyl
      substituent. Unfortunately, the final nucleosides (+/-)-3a and (+/-)-3b were
      found to be inactive against several viruses such as HIV-1, HSV-1, HSV-2 and
      HCMV.

PMID- 11339640
TI  - Effect of extracellular Mg concentration on electrically induced contractions of
      rat vas deferens in vitro.
AB  - Contraction of smooth muscles of the vas deferens plays an important role in the
      propulsion of sperm into the pelvic urethra. This study examined the influence of
      external Mg2+ concentration on reactivity of the rat vas deferens to electrical
      stimulation in vitro. Vasa deferentia isolated from adult male rats were set up
      in tissue baths containing physiological salt solution at 37 degrees C and were
      stimulated electrically. Thereafter, increasing concentrations of Mg2+ were added
      to the bath and their effects on electrically evoked contractions were recorded.
      The effect of external Mg2+ depletion on evoked contractions was also examined.
      External Mg2+ depletion enhanced the contractile response to electrical
      stimulation while increasing external Mg2+ concentration inhibited the
      contractions. The inhibitory effect of Mg2+ was partially reversed by increasing
      extracellular Ca2+ concentration and was not additive with nifedipine. The
      results indicate that reactivity of the vas deferens to electrical stimulation is
      modulated by extracellular Mg2+ concentration. The possible relevance of these
      data to sperm transport through the vas deferens is discussed.

PMID- 11339641
TI  - Phospholipid composition of human sperm and seminal plasma in relation to sperm
      fertility.
AB  - The phospholipid and fatty acid composition of sperm was studied in 8 healthy and
      16 infertile men. Infertile men randomly formed from the patients with normal
      semen parameters according to WHO criterion. Therefore, all semen parameters of
      infertile patients were similar to the same characteristics of the semen of
      healthy men, except the abnormal forms. The amount of abnormal forms in infertile
      men was significantly higher than in healthy men. Sperm from infertile men show a
      drastic loss of phosphatidyl ethanolamine. At the same time, the significant
      increase of phosphatidyl serine in the sperm and seminal plasma of sterile
      patients was found. Lysophosphatidyl serine in the sperm of the infertile men was
      detected. Fatty acid composition of the semen of infertile men was altered. The
      levels of stearic and n-3 polyunsaturated fatty acids (eicosopentaenoic and
      docosahexaenoic acids) was dramatically lowered, but the values of some n-6
      polyunsaturated fatty acids (linolenic and docosatetraenoic) acids increased.
      There was significant positive correlation between docosahexaenoic acid and sperm
      motility (r = .82, p < .001) and negative correlation between linolenic acid and
      spermatozoa motility (r = -0.58. p < .05). Infertility of men with normal semen
      quality can originate from the disorder of sperm lipid metabolism. The drastic
      loss of phosphatidyl ethanolamine and n-3 polyunsaturated fatty acids with
      simultaneous enhancement of phosphatidyl serine and some n-6 polyunsaturated
      fatty acids in sperm could be an important cause of male infertility.

PMID- 11339642
TI  - Increasing sperm concentration to adjust for subnormal sperm morphology did not
      adversely affect implantation after embryo transfer.
AB  - Some sperm specimens contribute to infertility not by impairing the fertilization
      process but by causing embryo implantation defects. One hypothesis is that a
      toxic factor attached to the sperm is transferred to the zona pellucida by the
      supernumerary sperm and then subsequently to the embryo membrane. One
      abnormality, as manifested by subnormal hypoosmotic swelling test (HOST) scores,
      causes these problems even with the small number of sperm that attach to the zona
      pellucida under normal physiologic conditions. This study evaluated whether the
      technique used to increase the oocyte insemination concentration of sperm to
      adjust for subnormal morphology values using strict criteria may allow a higher
      concentration of this purported toxic factor to attach to the zona pellucida,
      thus resulting in the dissimilitude of normal fertilization rate but low
      implantation rate. A comparison of the pregnancy and implantation rate of embryos
      formed by insemination of this adjusted sperm concentration of < or = 200,000
      sperm vs. those inseminated with the normal concentration of 25,000 sperm failed
      to demonstrate any differences. Thus, the technique of increasing sperm
      concentration to adjust for low sperm morphology to improve fertilization rates
      does not seem to adversely affect implantation rates as long as the HOST scores
      are normal.

PMID- 11339643
TI  - Lethal dose and reproductive parameters of p-nonylphenol in rats.
AB  - Male reproductive abnormalities may be due to an increased level of maternal
      estrogens affecting the developing fetus. Man is exposed to environmental
      estrogens in multiple ways: diet, drinking water, air, and skin, para-Nonylphenol
      (p-NP), an alkylphenol, has estrogenic properties. This study was performed to
      evaluate the potency and workable concentrations before reproductive tests could
      be performed. The oral LD50 (median lethal dose) value for rats was 1475 mg/kg.
      For both males in the reproductive test the litter size after long-term treatment
      at 50 mg/kg p-NP was smaller than that in the breeding records. Five females did
      not conceive at all.

PMID- 11339644
TI  - IgA antibodies to Chlamydia trachomatis and seminal parameters in asymptomatic
      infertile males.
AB  - Prevalence of IgA antibodies to Chlamydia trachomatis in semen samples from
      infertile men was estimated and its clinical meaning is discussed. The ejaculate
      of 102 infertile men without any symptom of genital infection was studied, and
      seminal alterations were classified according to WHO criteria. Antichlamydial IgA
      antibodies were detected using a solid-phase, enzyme-linked immunoassay
      (ImmunoComb II Chlamydia trachomatis monovalent IgA) and related to sperm count,
      motility and membrane integrity, seminal leucocyte count, and past history of
      sexually transmitted disease (STD). Prevalence of IgA antibodies to C.
      trachomatis was 23%. There was no relationship between IgA antibodies and the
      sperm variables or leucocyte count in semen. However, a strong association
      between antichlamydial IgA antibodies and the antecedent of STD was found (p <
      .005; OR = 6). IgA antibodies to C. trachomatis did not cause alterations in
      sperm function and they were not associated with inflammatory response. However,
      these antibodies in semen of asymptomatic infertile men would indicate a risk of
      C. trachomatis infection for the couples of those patients.

PMID- 11339645
TI  - Microvascular testicular blood flow as evaluated by laser Doppler flowmetry after
      the surgical induction of varicocele.
AB  - This study was conducted to evaluate the changes in microvascular testicular
      blood flow (microvascular TBF), which may be associated with varicocele. The
      pathology was developed through partial ligation of left renal vein in 4 groups
      of rats. Controls of each group underwent sham surgery. It was observed that
      microvascular TBF dropped and its vasomotion became inhibited once the left renal
      vein was partially ligated as studied by laser Doppler flowmetry (LDF). Four to
      five minutes later, blood flow rose to the pretreatment level and that of
      controls. Vasomotion reappeared with a uniform frequency and amplitude. At
      different periods of varicocele bearing (1, 3, 6, and 14 weeks) microvascular TBF
      was reevaluated. Vasomotion appeared intact without any abnormalities in the 4
      groups. To examine the response of testicular microvasculature after surgical
      creation of the varicocele to pharmacological stimulation another group of
      animals received human chorionic gonadotropin (hCG) treatment 6 weeks after
      varicocele creation. Vasomotion was inhibited in these animals. In conclusion,
      LDF is a suitable tool to evaluate microvascular TBF in vivo. It can detect acute
      changes in blood flow that may happen at surgical induction of varicocele. In
      addition, the vasculature of the testis with a surgically induced varicocele can
      still respond to hCG stimulation.

PMID- 11339646
TI  - Chromosomal abnormalities and polymorphisms in infertile men.
AB  - The aim of this study was to determine the prevalence of alterations and normal
      variable chromosome features in males from infertile couples. Karyotyping was
      performed to 84 men attending the infertility clinic at the Hospital Clinic i
      Provincial of Barcelona (Spain). Sex chromosome abnormalities were detected in 19
      patients (26.62%): 14 (16.67%) aneuploidies 47,XXY and 47,XYY, 3 (3.57%) Y
      chromosome long arm deletions; 1 (1.19%) mosaic 45,x/46,XY and 1 (1.19%)
      Robertsonian translocation (45.X-15-Y+t(15p: Yq). Chromosomal polymorphisms were
      observed in 29 patients. Yqh+ was the most frequent variant in sex chromosomes
      and increased length in heterochromatin and satellites were present in autosomal
      chromosomes. The high prevalence of chromosomal abnormalities observed in
      infertile men justify the use of karyotyping to evaluate males enrolled in new
      assisted reproductive technologies programs.

PMID- 11339647
TI  - Testicular sperm aspiration (TESA) and its application in oocyte donation.
AB  - This study was conducted to assess the outcomes of TESA in women undergoing
      oocyte donation. Descriptive reports from a university IVF practice were reviewed
      to evaluate the outcomes of women (n = 10) who underwent 12 cycles of ovum
      donation and required testicular sperm aspiration due to obstructive azoospermia
      (n = 6) and nonobstructive azoospermia (n = 4). Percutaneous needle aspiration of
      the testes was performed prior to oocyte retrieval to recover sperm, and
      intracytoplasmic sperm injection was subsequently performed on the donated
      oocytes. Fertilization was documented 16-18 h later and transcervical embryo
      transfer performed 72 h postretrieval. Successful retrieval of testicular
      spermatozoa utilizing the percutaneous technique was achieved in all 12 cycles.
      All cycles resulted in an ET with the achievement of 7 (58%) pregnancies, of
      which 5 (42%) are ongoing or delivered. The individual embryo implantation rate
      was 18.4% (9/49). Two cycles (16.6%) produced supernumerary embryos for
      cryopreservation. TESA represents a simple procurement technique associated with
      minimal morbidity. It may be offered even in cases of nondestructive azoospermia.

PMID- 11339648
TI  - Serum inhibin B as a marker for spermatogenesis.
AB  - Inhibin B generated by Sertoli cells provides negative feedback on FSH secretion.
      In men, inhibin B seems to be the physiologically important form of inhibin.
      Serum inhibin B was measured by two-site immunoenzymatic assay in 40 normal men
      (27 years of age) with sperm concentrations 100 +/- 9.2 x 10(6)/mL, 51 subfertile
      men (31 years of age) with sperm concentrations 6.8 +/- 0.8 x 10(6)/mL, 16 men
      with varicocele with sperm concentrations 54.3 +/- 0.8 x 10(6)/mL (31 years of
      age), men with hypogonadotrophic hypogonadism, men with Klinefelter syndrome, and
      men with obstructive and non-obstructive azoospermia. In men with normal sperm
      concentrations (>20 x 10(6) mL) serum inhibin B was 201 +/- 17 pg/mL and FSH 4 +/
      0.5 IU/L. Varicocele patients showed normal sperm concentrations > 20 x
      10(6)/mL, normal serum inhibin B (173 +/- 21 pg/mL), and normal FSH levels (4.6
      +/- 0.6 IU/L). In patients with sperm concentrations < 20 x 10(6)/mL the inhibin
      B level was 118 +/- 14 pg/mL and the FSH level was 10 +/- 1.1 IU/L. In all
      patients, except those with hypogonadotrophic hypogonadism and Klinefelter
      syndrome. inhibin B and FSH were inversely correlated (r = -.41, p > 0.01). There
      was a positive correlation between inhibin B and sperm concentrations (r = .34, p
      < .01). In varicocele men there was a correlation of r = .574, p < .05. Inhibin B
      may be a marker of exocrine testicular function and may offer an improved
      diagnosis of testicular dysfunction.

PMID- 11339649
TI  - Adenovirus-mediated p53 gene transfer to rat testis impairs spermatogenesis.
AB  - The tumor suppressor protein p53 participates in normal cell differentiation as
      well as induction of programmed cell death. The authors investigated the effect
      of p53 overexpression on spermatogenesis by transferring p53 gene into the rat
      testes. Replication-deficient recombinant adenovirus vectors were constructed to
      include cytomegalovirus (CMV) promoter driving wild-type p53 (Ad-CMV-p53) or beta
      galactosidase (Ad-CMV-beta-gal). Virus was delivered to cells of the tubules by
      slow retrograde injection through the rete testis. At 0, 4, 7, and 14 days,
      testes were removed, weighed, and analyzed histopathologically, including
      immunohistochemistry for p53, Bcl-2, Bax, and interleukin-1beta converting enzyme
      (ICE). Testicular weight was decreased in Ad-CMV-p53 group at 14 days after
      injection, while no change occurred in phosphate-buffered saline-injected
      controls or Ad-CMV-beta-gal-infected testes. Beyond 4 days, cell degradation in
      tubules interfered with immunohistochemical observation in the Ad-CMV-p53 group.
      At 4 days, p53 was expressed mostly in spermatocytes. Bax showed greater
      expression in the p53 group than in the control or Ad-CMV-beta-gal group. ICE,
      expressed mostly in spermatids, was more abundant in the p53 group than in
      controls. Overall, p53 overexpression in the testis impaired spermatogenesis.

PMID- 11339650
TI  - Mammography behavior after receiving a negative BRCA1 mutation test result in the
      Ashkenazim: a community-based study.
AB  - PURPOSE: To define the impact of a negative BRCA1 test result on subsequent
      breast cancer screening behavior in women. METHODS: Longitudinal study of a
      community-based sample of Ashkenazi Jews offered testing for the 185delAG BRCA1
      mutation in 1996. Of 309 participants, 118 women were mutation negative, of
      average risk (based on family history of cancer), unaffected with breast cancer,
      and provided complete data at baseline, and Year 1 and Year 2 follow-up
      questionnaires. RESULTS: Women age 50 and older had 91.7% compliance with
      mammography for the year prior to entry (baseline), 88.3% during Year 1, 91.7%
      during Year 2 (no significant change; P = 0.775). Women under age 50 demonstrated
      an increase in mammography (49.2% at baseline, 62.7% Year 1, and 67.1% Year 2; P
      = 0.035). Both groups demonstrated significant decreases in breast cancer worry
      and perceived risk. Logistic regression analysis on having a mammogram at Year 2
      showed that age, physician recommendation, worry, and perceived risk were all
      significant. CONCLUSION: Receipt of negative BRCA1 test results in a cohort of
      Ashkenazi Jewish women did not have a negative impact on mammography behavior 2
      years after genetic testing.

PMID- 11339651
TI  - Heterogeneity of late-infantile neuronal ceroid lipofuscinosis.
AB  - PURPOSE: Late-infantile neuronal ceroid lipofuscinosis (LINCL), an autosomal
      recessively inherited lysosomal storage disorder characterized by autofluorescent
      inclusions and rapid progression of neurodegeneration, is due to CLN2 gene
      mutations. However, CLN2 mutation analysis has failed to identify some clinically
      diagnosed "late-infantile" NCL cases. This study was conducted to further
      characterize genetic heterogeneity in families affected by LINCL. METHODS: DNA
      mutations in the CLN1, CLN2, and CLN3 genes that underlie INCL (infantile NCL),
      LINCL, and JNCL (juvenile NCL), respectively, were studied with molecular
      analyses. RESULTS: A total of 252 families affected by childhood NCL were
      studied. Of 109 families clinically diagnosed as having LINCL, 3 were determined
      to have either INCL or JNCL by identification of mutation(s) in CLN1 or CLN3. Six
      families diagnosed initially as having JNCL were found to have LINCL based on the
      finding of mutations in the CLN2 gene. In addition, several novel mutations were
      identified. CONCLUSIONS: Clinical and genetic heterogeneity of LINCL was
      demonstrated in nine LINCL families studied.

PMID- 11339652
TI  - The GM2 gangliosidoses databases: allelic variation at the HEXA, HEXB, and GM2A
      gene loci.
AB  - The GM2 gangliosidoses are a group of recessive disorders characterized by
      accumulation of GM2 ganglioside in neuronal cells. The genes responsible for
      these disorders are HEXA (Tay-Sachs disease and variants), HEXB (Sandhoff disease
      and variants), and GM2A (AB variant of GM2 gangliosidosis). We report the
      establishment of three relational locus-specific databases recording allelic
      variation at the HEXA, HEXB, and GM2A genes and accessed at the GM2
      gangliosidoses home page (http://data.mch.mcgill.ca/gm2-gangliosidoses).
      Submission forms are available for the addition of new mutations to the
      databases. The databases are available online for users to search and retrieve
      information about specific alleles by a number of fields describing mutations,
      phenotypes, or author(s).

PMID- 11339653
TI  - Congenital disorders of glycosylation: have you encountered them?

PMID- 11339654
TI  - Disorders of fatty acid transport and mitochondrial oxidation: challenges and
      dilemmas of metabolic evaluation.
AB  - Inborn errors of fatty acid transport and mitochondrial oxidation (FATMO) have
      drawn considerable attention in recent years for the rapid pace of discovery of
      new defects and an ever-increasing spectrum of clinical phenotypes. Several of
      these disorders are not detected by conventional biochemical investigations, even
      when a patient is symptomatic with fasting intolerance or functional failure of
      fatty acid dependent tissue(s). In our view, today's major challenges are the
      inclusion of FATMO disorders in newborn screening programs and the investigation
      of the role played by individual disorders in maternal complications of
      pregnancy, sudden and unexpected death in early life, and pediatric
      acute/fulminant liver failure. Dilemmas are found in the debate over the
      limitations, if any, to be imposed on the expansion of newborn screening using
      tandem mass spectrometry, in the provision of prenatal diagnosis for otherwise
      treatable disorders, and in the diagnostic workup of "unclassified" cases.

PMID- 11339656
TI  - The new computer slide programs allow for very complex and colorful
      transparencies to be created easily.

PMID- 11339655
TI  - Molecular diagnosis and inborn errors of metabolism: a practitioner's view.
AB  - Recombinant DNA technology has altered completely the face of genetics and its
      clinical practice. cDNAs for enzymes involved in inborn errors were among the
      first cloned, but the impact of this advance on our subspecialty has been more
      limited. This discussion addresses the uses and "abuses" of recombinant DNA
      technology in the field, and areas of greater or lesser usefulness in current
      practice, and the future, are discussed.

PMID- 11339657
TI  - In recent years, computer technology has seen advances which have had a major
      impact on the practice of medicine.

PMID- 11339658
TI  - Informed consent for medical photographs. Dysmorphology Subcommittee of the
      Clinical Practice Committee, American College of Medical Genetics.

PMID- 11339659
TI  - Technical and clinical assessment of fluorescence in situ hybridization: an
      ACMG/ASHG position statement. I. Technical considerations. Test and Technology
      Transfer Committee.

PMID- 11339661
TI  - Guidelines for expert witness testimony for the specialty of medical genetics.
      Social, Ethical and Legal Issues Committee, American College of Medical Genetics.

PMID- 11339660
TI  - Genetic testing for colon cancer: joint statement of the American College of
      Medical Genetics and American Society of Human Genetics. Joint Test and
      Technology Transfer Committee Working Group.

PMID- 11339662
TI  - Inhalation of low (0.5%-1.5%) CO2 as a potential treatment for apnea of
      prematurity.
AB  - Apnea of prematurity is common and none of the treatments being used are fully
      effective and free of significant adverse side effects. We hypothesized that low
      concentrations of CO2 (< or = 1.5%) may reduce apnea without causing discomfort
      from an increase in ventilation. We studied 10 preterm infants at a gestational
      age of 32+/-1 wk (mean +/- SEM) and birthweight 1.8+/-0.2 kg. After a control
      period of 1 hour, concentrations of CO2 were given (0.5%, 1%, and 1.5%) for 1
      hour each, followed by a recovery period of 1 hour. Apnea number significantly
      decreased from 2.0+/-0.3 apneas/min during control to 1.0+/-0.1 apneas/min (0.5%
      CO2; P < .05), 1.1+/-0.2 (1% CO2; P < .05), and to 0.7+/-0.2 (1.5% CO2; P < .01).
      The apnea time significantly decreased from 14.2+/-2.5 s/min during control to
      5.2+/-0.8 (0.5% CO2; P < .01), 5.8+/-0.7 (1% CO2; P < .01), and to 3.7+/-0.9
      (1.5% CO2; P < .01). Minute ventilation significantly increased with CO2 without
      evidence of respiratory discomfort. TcPCO2 did not change and TcPO2 increased
      slightly. These findings suggest that inhalation of low concentrations of CO2 in
      preterm infants with apnea 1) decreases the number and time of apneas, 2)
      improves oxygenation, 3) increases ventilation, and 4) is effective even in such
      low concentrations as 0.5%. We speculate that inhalation of CO2 (< 1%) is more
      effective and safer than methylxanthines for the treatment of apnea of
      prematurity.

PMID- 11339664
TI  - Capillary electrophoresis for the determination of albumin binding capacity and
      free bilirubin in jaundiced neonates.
AB  - This study develops a capillary electrophoresis/frontal analysis (CE/FA) method
      to separate free bilirubin from its albumin bound complex, with only small-sized
      samples. Under our optimized conditions, CE/FA is proven to be a simple and
      accurate method in assaying the concentration of free bilirubin in the jaundiced
      serum. Upon saturation of albumin-binding, the amount of bilirubin added to the
      serum bears a linear relationship with the absorbance at OD44OnM (R = .9987, P <
      .00001). Application of this method to study jaundiced neonates has yielded
      precise data on the residual binding capacity, which may be of significant
      therapeutic implications. The CE/FA method we have developed appears to be
      promising and applicable for clinical use as it is highly reproducible and it
      only requires a small sample size for tests. Our method should be an invaluable
      adjunct to the neonatal management of hyperbilirubinaemia.

PMID- 11339663
TI  - Implementation of guidelines for preventing early onset group B streptococcal
      infection.
AB  - Early onset Group B Streptococcus (EOGBS) disease, defined by an onset within the
      first 72 hours of life, occurs in 1.3 to 3.7 per 1,000 live births. The authors
      sought to determine the impact of the new CDC/AAP/ACOG guidelines on the
      prepartum screening practice, intrapartum management, incidence of EOGBS
      infection, and evaluation of neonates born to GBS colonized women at University
      Macdonald Women's Hospital (Cleveland, OH). A retrospective analysis by chart
      review was conducted from January 1, 1995 to December 31, 1997 of women
      identified as GBS colonized during prenatal screening. These women were then
      divided into 2 groups: period I, women who delivered January 1, 1995 to June 30,
      1996 (before institutional implementation of the guidelines for management of GBS
      colonization]; and period II, women who delivered July 1, 1996 to December 31,
      1997 after implementation of the guidelines. A chart review was conducted for
      infants 72 hours old, and GBS culture positive (blood or CSF) for the same time
      period. In complying with the new screening and treatment guidelines, there was a
      significant increase in the number of mothers screened and the detection of
      maternal colonization, plus a 63% reduction in EOGBS. There was also a
      substantial reduction in the number of invasive procedures on the neonates. The
      authors conclude that the new guidelines are both medically and economically
      effective.

PMID- 11339665
TI  - Photoprotection of solutions of parenteral nutrition decreases the infused load
      as well as the urinary excretion of peroxides in premature infants.
AB  - Light exposure and multivitamins are contributing factors to the generation of
      peroxides in solutions of parenteral nutrition. This article verifies if
      peroxides infused with parenteral nutrition are of biological significance in
      neonates. The mechanisms responsible for the generation of peroxides in total
      parenteral nutrition solutions are reviewed. The consequences of infused
      peroxides on an index of oxidant stress and on levels of a central antioxidant
      are evaluated in an animal model. The effect of photoprotection of parenteral
      nutrition on a biological marker of redox imbalance is evaluated in the urine of
      premature infants. Parenteral multivitamins produce a drop in glutathione and an
      oxidant stress similar to peroxides in the lungs of newborn guinea pigs. Infused
      peroxides elicited an increased urinary peroxide excretion in infants receiving
      parenteral nutrition exposed to light. Photoprotection reduced levels of infused
      and excreted peroxides. The results suggest that peroxides infused with total
      parenteral nutrition are not fully quenched by premature infants.

PMID- 11339666
TI  - Peripheral fractional oxygen extraction and other measures of tissue oxygenation
      to guide blood transfusions in preterm infants.
AB  - The physiological effects of anemia in the preterm infant are complex and the
      indications for transfusions in preterm infants are controversial. A measure of
      the adequacy of tissue oxygenation may be a better guide to the need for
      transfusions than currently used criteria. This article considers 2 measures of
      tissue oxygenation of preterm infants: 1) The whole blood lactate concentration,
      and 2) Peripheral fractional oxygen extraction (FOE) by using near infrared
      spectroscopy. Several studies have shown falls in blood lactate concentration
      after blood transfusion, but it has been difficult to establish a convincing link
      between raised lactate concentrations and significant anemia because even anemic
      infants have lactate concentrations that are within or close to the normal range.
      Lactate concentrations may be affected by the haematocrit of the blood sample.
      Peripheral FOE can be measured by using near infrared spectroscopy with partial
      venous occlusion and has been studied in preterm infants with symptomatic and
      asymptomatic anaemia. Mean (SD) FOE was significantly higher in symptomatic
      [0.425 (0.06)] (P< .01) but not asymptomatic [0.334 (0.05)] compared to controls
      [0.352 (0.06)], (P = .22). After transfusion there was a significant fall in FOE
      in symptomatic infants to 0.367 (0.06) (P = .001) but there was no change in
      infants who were asymptomatic. FOE correlated with other measures known to
      reflect the adequacy of oxygen availability during anemia. These results suggest
      that peripheral FOE may be suitable as a guide to the need for blood
      transfusions. A pilot randomized controlled trial is currently being undertaken
      to test this hypothesis.

PMID- 11339667
TI  - Group B Streptococci and inducible nitric oxide synthase: modulation by nuclear
      factor kappa B and ibuprofen.
AB  - Group B Streptococci (GBS) neonatal infections cause a complex inflammatory
      process involving numerous biochemical mediators. Nitric Oxide (NO) is generated
      by many cell types in response to different inflammatory signals. Nuclear factor
      kappa B (NFkappaB) plays an important role in the inflammatory process and may
      induce a number of biochemical mediator genes, including the inducible nitric
      oxide synthase (iNOS). We tested the hypothesis that GBS induces iNOS gene
      expression through activation of NFkappaB. We also tested whether ibuprofen (IBU)
      will suppress iNOS expression by blocking NFkappaB activation. Cerebral
      microvascular endothelial cells isolated from newborn piglets were harvested for
      the determination of iNOS gene expression and activation of NFkappaB. GBS
      significantly induced iNOS mRNA expression (5- to 6-fold, P < .005) and iNOS
      protein (3- to 4-fold, P < .01) at 24 hours. DNA-NFkappaB binding activity was
      detected within 15 minutes of GBS treatment and reached a maximal effect at 3
      hours. Treatment with IBU significantly suppressed GBS-induced iNOS mRNA
      expression at 24 hours, and NFkappaB activity at 3 hours, suggesting that
      suppression of GBS-induced iNOS mRNA expression by IBU occurs by blocking of
      NFkappaB activation. These data show that NFkappaB activation is an early step in
      the induction of iNOS gene expression by GBS and that this interaction may play a
      vital role in the pathogenesis of GBS neonatal infections.

PMID- 11339669
TI  - Developmental aspects of parathyroid hormone-related protein biology.
AB  - Parathyroid hormone-related protein (PTHrP) has been discovered as a parathyroid
      hormone (PTH)-like factor responsible for the humoral hypercalcaemia of
      malignancies. Further studies revealed that PTHrP is ubiquitously expressed, in
      mature as well as in developing normal tissues from various species. Although not
      completely understood, the biological roles of PTHrP concern a variety of
      domains, including calcium phosphorus metabolism and bone mineralization, smooth
      muscle relaxation, cell growth and differentiation, and embryonic development. As
      a poly-hormone, PTHrP is now acknowledged to act via the paracrine, autocrine,
      and even the intracrine pathways. This review focuses on the main developmental
      features of the biology of PTHrP. During embryonic development, PTHrP is
      considered to be involved as a growth factor that promotes cell proliferation and
      delays cell terminal maturation. PTHrP has been shown to intervene in the
      development of various tissues and organs such as the skeleton, skin, hair
      follicles, tooth, pancreas, and the kidney. In addition, through its midregion
      sequence, which is able to promote an active transplacental calcium transport,
      PTHrP may intervene indirectly in the mineralization of the foetal skeleton.
      PTHrP has also been shown to be necessary for the normal development of the
      mammary gland, while huge amounts of PTHrP are found in the human milk. Finally,
      observations of physiologic, vasodilating effects of PTHrP in the kidney suggest
      its involvment in the control of renal hemodynamics, especially in the perinatal
      period.

PMID- 11339668
TI  - Characterization of PGE2 receptors in fetal and newborn ductus arteriosus in the
      pig.
AB  - We compared the total density and the relative expression of EP receptor (EP)
      subtypes in ductus arteriosus (DA) of the newborn with that of the fetal piglet.
      Saturation binding experiments showed 3-fold less PGE2 receptors in the newborn
      than in the fetus because of loss of EP3 and EP4 receptors thus explaining, at
      least partly, the reduced responsiveness to PGE2 of the newborn DA. Displacement
      experiments showed that the relative proportions of EP2, EP3, and EP4 were
      similar in the fetal DA but only EP2 was detected in the DA of the newborn pig.
      Hence, PGE2 effects in the newborn DA seem to be exclusively mediated by EP2
      receptors both in vitro and in vivo. These findings may help to propose more
      specific therapies for regulation of DA's tone in certain newborns for whom
      conventional therapy is contraindicated.

PMID- 11339670
TI  - Carbon monoxide and bilirubin production in neonates.
AB  - Neonatal hyperbilirubinemia is a normal postnatal phenomenon resulting from a
      transitional imbalance between the production and elimination of bilirubin in the
      neonate. Bilirubin has been shown to be not only a potent antioxidant, but also
      toxic at excessive concentrations. As a result, the biology of bilirubin, its
      production, regulation, and measurements have been the focus of extensive
      studies. Bilirubin, carbon monoxide, and iron are derived from the degradation of
      heme, a ubiquitous two-step pathway catalyzed by the enzyme, heme oxygenase. It
      has been shown that these metabolically active products from the heme catabolic
      pathway may, in turn, influence many other biologic processes. This report
      provides a brief overview of these interrelationships in the hope that it may
      provide insight into the central role this pathway plays in the existence of most
      organisms.

PMID- 11339672
TI  - Children's environmental health risks: a state-of-the-art conference.
AB  - More than 100 academic and private-sector researchers, government officials,
      politicians, and public health practitioners met to discuss issues regarding
      children's environmental health. Of special concern were the lack of
      toxicological data on many chemicals, the paucity of studies of children's
      exposure to these chemicals, and our limited understanding of pediatric
      toxicology. The increased incidence of childhood cancers and asthma were also of
      concern, as was our lack of understanding of how exposures to multiple
      environmental chemicals in low doses may influence child growth and development,
      disrupt endocrine function, and stimulate development of chronic diseases. An
      agenda for basic research, education and outreach, and policy and program
      development was created, with a goal of moving children's environmental health
      issues forward in a logical and thoughtful manner.

PMID- 11339671
TI  - Effect of antenatal dexamethasone on the expression of endothelial nitric oxide
      synthase in the lungs of postnatal pups.
AB  - Activities of endothelial nitric oxide synthase (eNOS) are developmentally
      regulated and its presence at birth may play a role in the transition of
      cardiopulmonary circulation. Antenatal dexamethasone (Dex) therapy accelerates
      fetal lung maturation. We speculate that Dex therapy may enhance pulmonary eNOS
      protein expression in the newborn. This article examines whether antenatal Dex
      therapy affected the expression of eNOS in the lungs of rat pups in the postnatal
      period. Time-dated pregnant Wistar rats were subjected to 2 doses of Dex (0.8
      mg/kg, intramuscularly, daily) or equivalent volume of normal saline at the 18th
      and 19th gestational day and delivered naturally. The newborn pups were randomly
      assigned to 4 groups by age: days 1, 3, 5, and 7. After homogenization, abundance
      of eNOS protein in lungs was determined by Western blot analysis. There were 7
      dams in each group. Mean body weights of the pups in the Dex group were lighter
      than those in the control at birth and remained stunted up to day 7 (5.68+/-0.47
      g v 6.34+/-0.47 g, P <.01). However, there were no differences in wet lung
      weights and lung/body weight ratios between both groups in the study period.
      Abundance of eNOS protein expression decreased in both the control and Dex groups
      (P < .01). Pups that received antenatal Dex had 39% more in abundance of eNOS
      protein expression in lungs when compared to the control on day 1 (P < .05) but
      there were no differences between both groups from day 3 to 7. We conclude that
      antenatal Dex therapy enhances the abundance of eNOS protein expression in the
      lung at birth and could be a factor in improving respiratory functions in infants
      who received antenatal steroid therapy.

PMID- 11339673
TI  - Puzzling elevation of blood lead levels among consumers of freshwater sportfish.
AB  - The authors evaluated lead exposure of Canadians (Montreal) who fished the nearby
      St. Lawrence River. From screening interviews conducted with 1,118 fishers on
      site during the winter and fall of 1996, the authors selected 60 Montrealers who
      consumed at least one sportfish meal per week and 72 who consumed less than one
      sportfish meal per week. Fishers at the higher level of sportfish consumption had
      elevated blood lead concentrations, compared with fishers who ate little
      sportfish (geometric mean = 57.4 microg/l vs. 48.2 microg/l, respectively; p <
      .05). This result was surprising inasmuch as fish is not considered a significant
      source of lead. In addition to sportfish consumption, age, sex, occupation,
      smoking, and waterfowl consumption also showed independent associations with
      blood lead levels. Among frequent (i.e., > or = 1 meal/wk) consumers of
      sportfish, ingestion of waterfowl was associated with higher blood lead levels
      (geometric mean = 69.4 microg/l vs. 51.8 microg/l, respectively; p < .05); this
      association was not present for infrequent consumers. In multivariate analysis,
      the association of higher blood lead levels with sportfish consumption could be
      accounted for in large part by waterfowl consumption among frequent consumers of
      sportfish.

PMID- 11339674
TI  - Passive smoking in children: effect of avoidance strategies, at home as measured
      by hair nicotine levels.
AB  - Hair nicotine levels were studied among children, relative to their caregivers'
      reported exposure to environmental tobacco smoke. A total of 117 children, aged 3
      months to 10 years, were recruited consecutively from hospital inpatients, and
      their respective parents or caregivers were interviewed. Degree of exposure to
      environmental tobacco smoke was assessed via questionnaire. Scalp hair samples
      were collected from children and were assayed for nicotine. Levels of nicotine in
      hair among children reportedly exposed to smokers were higher than levels among
      unexposed children (chi2 = 26.46, p < .0001). In addition, hair nicotine levels
      were higher among children with mothers who smoked, compared with those whose
      mothers did not smoke. Whether household members smoked outside or inside the
      house had no significant effect on hair nicotine levels of children. Hair
      nicotine levels differed between children who were reportedly unexposed to
      environmental tobacco smoke at home and those who were exposed. Smoking outside
      the home, as reported by parents, did not cause a reduction in nicotine levels in
      the hair of children.

PMID- 11339675
TI  - Health effects from chronic low-level exposure to hydrogen sulfide.
AB  - The acute toxic effects of hydrogen sulfide have been known for decades. However,
      studies investigating the adverse health effects from chronic, low-level exposure
      to this chemical are limited. In this study, the authors compared symptoms of
      adverse health effects, reported by residents of two communities exposed mainly
      to chronic, low-levels of industrial sources of hydrogen sulfide, to health
      effects reported by residents in three reference communities in which there were
      no known industrial sources of hydrogen sulfide. Trained interviewers used a
      specially created, menu-driven computer questionnaire to conduct a multi-symptom
      health survey. The data-collection process and questions were essentially the
      same in the reference and exposed communities. The two exposed communities
      responded very similarly to questions about the major categories. When the
      authors compared responses of the exposed communities with those of the reference
      communities, 9 of the 12 symptom categories had iterated odds ratios greater than
      3.0. The symptoms related to the central nervous system had the highest iterated
      odds ratio (i.e., 12.7; 95% confidence interval = 7.59, 22.09), followed by the
      respiratory category (odds ratio = 11.92; 95% confidence interval = 6.03, 25.72),
      and the blood category (odds ratio = 8.07; 95% confidence interval = 3.64,
      21.18). Within the broader health categories, individual symptoms were also
      elevated significantly. This study, like all community-based studies, had several
      inherent limitations. Limitations, and the procedures the authors used to
      minimize their effects on the study outcomes, are discussed. The results of this
      study emphasize the need for further studies on the adverse health effects
      related to long-term, chronic exposure to hydrogen sulfide.

PMID- 11339676
TI  - Function testing for chemical brain damage: a review.
AB  - Testing of neurobehavioral functions for evaluation of the effects of chemicals
      on the human brain from community (i.e., environmental) exposures is logical and
      may be a preferred initial step. Sensitivity is improved (1) by adjusting
      individual tests for influential factors, found by regression modeling and by
      retaining significant coefficients; and (2) by the calculation of predicted
      values for each test for each subject. This two-part approach allows for
      adjustments in age, sex, educational level, and other factors before comparisons
      are made. Visual fields, color discrimination, reaction time, balance, and digit
      symbol are the most sensitive tests, followed by 6 sensitive psychological tests
      and less-discriminating physiological measurements. Hydrogen sulfide,
      polychlorinated biphenyls, and arsenic are the most toxic chemicals, followed by
      chlorine, chlorpyrifos, formaldehyde, nickel carbonyl, and ammonia. The least
      toxic chemicals, which are hydrochloric acid and chlorine, were determined 7 wk
      following a community spill. The least toxic chemical among those identified
      herein is methyl ter butyl ether.

PMID- 11339677
TI  - Plasma levels of persistent organohalogens and hormone levels in adult male
      humans.
AB  - In this study the authors assessed the possible relationship between high dietary
      exposure to persistent organohalogens (OHS) through fatty fish from the Baltic
      Sea and hormone levels in adult men. Blood samples were drawn from 110 men who
      consumed varying amounts of fish (i.e., 0-32 meals per month) for analysis of
      plasma levels of 18 polychlorinated biphenyl (PCB) congeners, 5 hydroxy-PCBs,
      1,1,1-trichloro-2,2-bis(4-chlorophenyl)-ethane (p,p'-DDT), 1,1-dichloro-2,2-bis(4
      chlorophenyl)-ethene (p,p'-DDE), hexachlorobenzene, and 2,2',4,4'
      tetrabromodiphenyl ether. In addition, plasma levels of follicle-stimulating
      hormone, luteinizing hormone, prolactin, plasma thyrotropin, free and total T3,
      free and total T4, and free testosterone were analyzed. The authors adjusted for
      age, and the only significant associations that remained were negative
      correlations between 2,2',4,4'-tetrabromodiphenyl ether and plasma thyrotropin (p
      < .001), and between pentachlorophenol and follicle-stimulating hormone (p =
      .04). The authors expected that there would be some significant correlations that
      resulted from pure chance. High consumption of organohalogen-polluted fish did
      not appear to affect plasma concentrations of pituitary, thyroid, or testosterone
      hormone levels in male adults.

PMID- 11339678
TI  - Fungal exposure of children at homes and schools: a health perspective.
AB  - The authors investigated airborne fungal exposure of Taiwanese children at homes
      and schools-locations where they spent the majority of their time. Pairs of
      asthmatic and healthy children, matched by age, gender, classes (schools), and
      residence, participated in the study. Airborne fungal concentrations at homes and
      schools, and time-activity data of the study subjects were collected. In winter,
      the indoor geometric mean concentration was 9,672.1 colony-forming units per
      cubic meter and 4,380.9 colony-forming units per cubic meter in summer. The
      indoor/outdoor concentration ratio was similar in all homes for both seasons.
      Fungal concentrations in southern Taiwan were high during both winter and summer.
      Personal fungal exposure was not statistically different between asthmatic and
      nonasthmatic children, after adjustment of time-activity patterns. Higher symptom
      scores were shown for children in homes with higher fungal exposures.

PMID- 11339679
TI  - Ultrafine particles in human lung macrophages.
AB  - As knowledge about size dependency of particle toxicity continues to grow,
      attention has been focused on ultrafine particles (i.e., < 0.1 microm in
      diameter). In recent studies with rats, investigators learned that ultrafine
      particles likely have greater pulmonary toxicity than larger particles, and it is
      possible that exposure to, and accumulation of, these particles in the human lung
      may be associated with adverse respiratory health effects. As part of an ongoing
      study, the authors performed bronchoalveolar lavage in 14 healthy current
      nonsmokers to investigate the extent to which ultrafine particles were present in
      lung macrophages. In addition, 10 of the 14 subjects performed pulmonary function
      tests. Eleven of the 14 subjects were utility workers, and 3 were nonmaintenance
      employees of a university. The authors used a Zeiss CEM902 electron microscope to
      study macrophages isolated from bronchoalveolar lavage fluid. Morphometric
      quantification revealed ultrafine particles in lung macrophages of all 14
      volunteers; the average number of ultrafine particles/microm3 cytoplasm per cell
      (UFavg) ranged from 34 to 231 (mean = 95, standard deviation = 54). Regression
      analysis showed that the UFavg was associated inversely with percent predicted
      forced expiratory volume in 1 second (FEV1.0) (beta = -1.2 percent predicted
      FEV1.0/10 ultrafine particles x microm3 cytoplasm per cell [standard error =
      0.45, p = .031). The demonstration of ultrafine particles in all 14 subjects,
      independent of occupational exposure, suggests that there is environmental
      exposure to ultrafine particles. The negative association between the number of
      ultrafine particles and ventilatory function demonstrates a need for further
      investigation into the pulmonary health effects of ultrafine particles.

PMID- 11339680
TI  - Recent chemical exposures and blood volatile organic compound levels in a large
      population-based sample.
AB  - Little is known about factors that influence blood levels of volatile organic
      compounds in nonoccupationally exposed populations. The authors examined the
      possible relationship between recent self-reported chemical exposures and
      elevated blood volatile organic compound levels among 982 adult participants in
      theThird National Health and Nutrition Examination Survey. A strong dose-response
      effect was indicated (p < .001) for increasing lifetime pack-years of cigarettes
      smoked for elevated levels of toluene, styrene, and benzene. A positive dose
      response effect was indicated for daily alcohol consumption with respect to
      elevated blood levels of 2-butanone and acetone. For volatile organic compounds
      typically found in 10-75% of the population, the establishment of a link with
      specific environmental exposures is relatively easy because there is less effect
      of confounding in this group. Some volatile organic compounds, however, are seen
      in less than 10% of the general population; finding these compounds at any level
      may warrant a search for a particular exposure.

PMID- 11339681
TI  - Traffic-related air pollution affects peak expiratory flow, exhaled nitric oxide,
      and inflammatory nasal markers.
AB  - The authors used a longitudinal observational design, with repeated measures, to
      study the association between traffic-related air pollutants (i.e., nitric oxide,
      nitrogen dioxide, carbon monoxide, and Black Smoke) and respiratory symptoms.
      Subjects (N = 82) attended an elementary school in either Utrecht (i.e., urban
      children) or Bilthoven (i.e., suburban children). These two geographic areas
      differed with respect to levels of Black Smoke (means = 53 microg/m3 and 18
      microg/m3, respectively). Levels of nitric oxide, nitrogen dioxide, carbon
      monoxide, and Black Smoke were consistently higher in Utrecht than in Bilthoven
      (mean daily ratios were 8, 1.5, 1.8, and 2.7, respectively). The authors compared
      mean levels of short-term effects of the aforementioned air pollutants on
      suburban and urban children. Urban children had higher mean levels (p = .05) of
      interleukin-8 (32%), urea (39%), uric acid (26%), albumin (15%), and nitric oxide
      metabolites (21%) in nasal lavage than did suburban children. Peak expiratory
      flow, exhaled nitric oxide levels, and nasal markers were associated with levels
      of particulate matter with diameters less than or equal to 10 microm, Black
      Smoke, nitrogen dioxide, and nitric oxide. With respect to per-unit increases in
      air pollution, urban children had more increased peak expiratory flow, higher
      levels of exhaled nitric oxide, and more increased release of uric acid, urea,
      and nitric oxide metabolites than suburban children. In summary, urban children
      had increased levels of inflammatory nasal markers, and their responses were more
      pronounced than were the suburban children's responses to the same increments of
      air pollution.

PMID- 11339682
TI  - Respiratory sinus arrhythmia in persons with organic solvent exposure:
      comparisons with anxiety patients and controls.
AB  - Persons exposed to organic solvents have psychiatric symptomatology and cognitive
      impairments. The results of several studies have suggested that some psychiatric
      symptoms in these patients reflect similar reactions observed in patients with
      anxiety disorders. Respiratory sinus arrhythmia provides an indication of
      impaired autonomic functioning. Whereas decreased respiratory sinus arrhythmia
      has been reported in anxiety patients, investigators have also noted that higher
      respiratory rates in these patients obscure differentiation of respiratory sinus
      arrhythmia from normal values. In this study, the authors recorded multiple
      parameters of respiratory sinus arrhythmia under a paced-breathing condition in
      28 patients with solvent exposure, in 18 patients with anxiety disorder, and in
      31 controls. The authors observed a high 1-y retest reliability for a subset of
      the subjects. Significantly reduced respiratory sinus arrhythmia was observed in
      both anxiety and solvent-exposed patients, compared with controls. Maximum mean
      heart rates/cycle did not differ among groups, but minimum heart rates were
      significantly lower for controls than for the two patient groups. The findings
      suggested that reduced respiratory sinus arrhythmia among patients is not related
      to higher maximum rates but, rather, to a decrease in vagally mediated alteration
      associated with respiratory changes observed in both patient groups.

PMID- 11339683
TI  - Hydraulic fluids and jet engine oil: pyrolysis and aircraft air quality.
AB  - Incidents of smoke in aircraft cabins often result from jet engine oil and/or
      hydraulic fluid that leaks into ventilation air, which can be subjected to
      temperatures that exceed 500 degrees C. Exposed flight-crew members have reported
      symptoms, including dizziness, nausea, disorientation, blurred vision, and
      tingling in the legs and arms. In this study, the authors investigated pyrolysis
      products of one jet engine oil and two hydraulic fluids at 525 degrees C. Engine
      oil was an important source of carbon monoxide. Volatile agents and
      organophosphate constituents were released from all the agents tested; however,
      the neurotoxin trimethyl propane phosphate was not found. The authors
      hypothesized that localized condensation of pyrolysis products in ventilation
      ducts, followed by mobilization when cabin heat demand was high, accounted for
      mid-flight incidents. The authors recommended that carbon monoxide data be logged
      continuously to capture levels during future incidents.

PMID- 11339684
TI  - Manganese in lung tissue: study of Mexico City residents' autopsy records from
      the 1960s and 1990s.
AB  - During the conduct of autopsies performed on residents of Mexico City during the
      1960s (20 males, 19 females) and 1990s (30 males and 18 females), concentrations
      of manganese in lung were studied with atomic absorption spectrometry.
      Concentrations of manganese were not significantly greater in the samples
      obtained in the 1990s (1.87+/-0.8 microg/gm [mean +/- standard deviation]) than
      in samples from the 1960s (1.72+/-1.2 microg/gm). Concentrations were not
      correlated with gender, smoking habit, age, or cause of death; however, there was
      a correlation with occupation. The findings suggest that manganese exposure via
      air does not represent a health hazard to residents of Mexico City, given that
      lung concentrations of manganese remained stable during the 30-y period studied.
      Investigators should monitor concentrations of manganese in suspended particles
      to follow-up on these findings.

PMID- 11339685
TI  - At receptor inhibition affects the noradrenaline sensitivity in isolated portal
      vein of normotensive rat.
AB  - Short term treatments of normotensive Wistar Kyoto rats with angiotensin II
      (ANGII) or in combination with the AT1 receptor antagonist, losartan or PD123319,
      the AT2 receptor antagonist on systemic arterial blood pressure (MABP) and their
      influence on noradrenaline sensitivity in isolated mesenteric portal vein were
      evaluated. ANGII increased MABP as well as the contractile response to
      noradrenaline in vessels from ANGII-treated animals. MABP and the maximal effect
      of the concentration response curve for noradrenaline were prevented by losartan.
      However, PD123319 did not influence the blood pressure, but completely removed
      the vessels sensitivity to noradrenaline. ANGII combined with the AT1 and/or AT2
      receptors blockade completely prevented the pressure response to ANGII, but the
      concentration response curve for noradrenaline did not differ from the vehicle
      treated control curve. In conclusion both AT1- and AT2 receptor activation seems
      to be important in controlling noradrenaline sensitivity of rat portal vein
      smooth muscle.

PMID- 11339686
TI  - Effects of calcium antagonist, benidipine, on the progression of chronic renal
      failure in the elderly: a 1-year follow-up.
AB  - The number of patients who needs for dialysis therapy is increasing rapidly among
      the older population. Although control of hypertension can delay or arrest the
      progression of renal failure, there are lacking of studies about antihypertensive
      treatment of chronic renal failure in the elderly. We have studied the effects of
      treating hypertension with a calcium antagonist, benidipine, on renal function
      and blood pressure in 58 patients (mean age: 71 +/- 9) with hypertension and
      chronic renal insufficiency (the levels of creatinine ranging from 1.5 to 4.0
      mg/dl). The underlying disease included glomerulopathies (in 33), diabetic
      nephropathy (in 15), and other causes (in 10). Forty two patients who had been
      treated with other antihypertensive drugs other than angiotensin converting
      enzyme (ACE) inhibitors, antihypertensive drugs were withdrawn 2 weeks before the
      entry. At the entry, patients should have sitting systolic blood pressure (SBP)
      of above 160 mmHg and diastolic blood pressure (DBP) of above 90 mmHg. In total,
      both SBP and DBP decreased from 169/95+/-12.5/8.9 to 148/81+/-16.1/8.0 mmHg
      (p<0.001) with remaining the serum creatinine levels from 2.2+/-0.8 vs 2.4+/-1.3
      mg/dl (P>0.05). Retrospective analysis revealed that in 4 of 4 patients treated
      with benidipine and 2 of 3 patients with benidipine and ACE inhibitors with
      systolic blood pressure more than 160 mmHg at the end of the study, the levels of
      serum creatinine increased from 2.5+/-0.3 to 2.8+/-0.4 with significance
      (P<0.05). If systolic blood pressure was reduced less than 159 mmHg, 38 of 48
      patients did not show any deterioration of renal function. Compared to the
      significance of SBP in preserving renal function, DBP did not associate with the
      changes in renal function. No patients died during the study. One patient had
      transient ischemic attack and one patient had stroke in benidipine treated group.
      One patient had angina pectoris in benidipine-ACE inhibitors treated group. The
      results of our trial seem to give some support for the idea that long-acting
      calcium antagonists such as benidipine are renoprotective through reduction of
      SBP in the elderly people with hypertension and chronic renal insufficiency.
      However, if systolic blood pressure was not reduced below 160 mmHg throughout a
      year, the substantial declines in renal function would be expected.

PMID- 11339687
TI  - Ambulatory blood pressure monitoring and clinical characteristics of the true and
      white-coat resistant hypertension.
AB  - The resistant hypertension has been differentiated in true resistant hypertension
      and white-coat resistant hypertension by using ambulatory blood pressure
      monitoring. White-coat resistant hypertension was defined as high clinic blood
      pressure, despite triple treatment for at least 3 months, but day-time blood
      pressure values < 135/85 mmHg. The aim of this study was to evaluate the presence
      of different clinical characteristics between two types of resistant
      hypertension. The study group consisted of 49 patients with essential
      hypertension, resistant to an adequate and appropriate triple-drug therapy, that
      included a diuretic, with all 3 drugs prescribed in near maximal doses and that
      had persistently elevated clinic blood pressure (> 140/90 mm Hg), for at least 3
      months. They represented the 2% of 2500 hypertensive outpatients that referred at
      our Hypertension Unit. Patients with white-coat resistant hypertension (n=19)
      were older (p<0.05) than those with true resistant hypertension (n=30). The
      sodium intake (p<0.05) and alcohol intake (p<0.05) were significantly higher in
      patients with true resistant hypertension than in those with white-coat resistant
      hypertension. The renin plasma activity and plasma aldosterone were higher
      (p<0.05) in patients with true resistant hypertension than in those with white
      coat resistant hypertension with normal plasma electrolyte balance. There were no
      significant differences in mean values of office systolic and diastolic blood
      pressures between white coat resistant hypertensives and true resistant
      hypertensives (165+17 vs 172+28 and 98+12 vs 102+14 mmHg). Day-time and night
      time ambulatory 24-h-systolic and diastolic blood pressures were significantly
      higher in the true resistant hypertensive patients when compared with white-coat
      resistant hypertensives (153+15 vs 124+10 mmHg and 97+9 vs 76+6 mmHg all
      p<0.001). Day-time and night-time ambulatory 24-h-heart rate were significantly
      higher in the true resistant hypertensive patients when compared with white-coat
      resistant hypertensives (79+11 vs 71+9 beats/min; p<0.01; 68+9 vs 60+6 beats/min,
      p<0.001). The ABP readings were analysed by a Fourier series with 4 harmonics.
      According to the runs test both two groups of patients showed a circadian rhythm
      for both systolic and diastolic blood pressure. The nocturnal fall in SBP, DBP
      and HR was not different in both groups of patients. In conclusion, our findings
      showed that true resistant hypertensive patients were characterized both by
      higher heart rate and higher plasma renin activity values as an expression of a
      possible increased sympathetic activity. Thus, the combination of ABPM with the
      assessment of the clinical characteristics allow to differentiate better the true
      drug-resistant hypertension from the white coat resistant hypertension.

PMID- 11339688
TI  - Salt-sensitivity and other predictors of stress-related cardiovascular reactivity
      in healthy young males.
AB  - Individuals whose mean arterial blood pressure is depending on oral salt intake
      are considered salt-sensitive and are at risk of developing essential
      hypertension. This study investigates the role of salt-sensitivity with respect
      to systolic blood pressure reactions under standardized mental stress. Forty
      three healthy young males, previously characterized as salt-sensitive (n=16) or
      salt-resistant (n=27) by a dietary regimen, were subjected to multimodal
      physiological measurement during a computerized stress test and underwent
      comprehensive psychometrical testing. The most important predictors for systolic
      blood pressure reactions to stress were the degree of salt-sensitivity, body mass
      index and psychological characteristics like anxiety. The highest correlations
      with the degree of salt-sensitivity were found for the parameters age, systolic
      blood pressure reaction under stress, high frequency band of heart rate
      variability and two psychological variables. The concept of salt-sensitivity is a
      novel biological component that might contribute to reactivity research in
      subjects at high risk for essential hypertension.

PMID- 11339689
TI  - Obese female SHHF/Mcc-fa(cp) rats resist antihypertensive effects of renin
      angiotensin system inhibition.
AB  - Gender and obesity may influence response to pharmacological modulation of the
      renin-angiotensin system. We used SHHF/Mcc-fa(cp) rats to study effect of obesity
      and gender on the ability of an AT1 receptor antagonist to decrease blood
      pressure. After 2 weeks treatment with irbesartan (50 mg/kg), only lean and obese
      males showed significant decreases in blood pressure, while obese females were
      completely resistant. Lean females showed a trend toward lowering of pressure
      (p=0.06). However, irbesartan similarly shifted angiotensin II dose response
      curves to the right in all groups. Twelve weeks of irbesartan also failed to
      decrease blood pressure, but did significantly reduce heart weight in obese
      females. In untreated rats, obese females had lower plasma renin activity and
      serum angiotensin converting enzyme activity compared to lean males, while lean
      and obese females had increased urinary endothelin excretion. Despite an
      otherwise similar genetic background contributing to hypertension and heart
      failure, obese females have different patterns of humoral activation compared to
      lean males, which may contribute to their resistance to the depressor effects of
      irbesartan.

PMID- 11339690
TI  - The role of gender in salt-induced hypertension.
AB  - To evaluate gender differences in salt-induced hypertension, female and male Dahl
      salt-sensitive rats were fed high (8.0% NaCl, HS) and low (0.3% NaCl, LS) salt
      diets. During a 3-week treatment period, blood pressure was significantly
      elevated in both female and male HS groups compared to their respective LS
      groups. The blood pressure and 4 week mortality rate of the female HS group,
      however, were significantly lower than those of the male HS group. Renal and
      aortic blood flows were reduced in male rats on HS diet compared to the LS group,
      while, in females, renal blood flow was elevated and aortic flow was maintained
      while on HS diet. Plasma prostaglandin E2 and prostacyclin levels were higher in
      females than males and unaffected by diet. In contrast, plasma nitric oxide
      levels were reduced by HS, regardless of gender. In isolated aortic rings, HS
      diet caused a smaller elevation in the stimulated norepinephrine release ratio in
      female rats than in males. Thus, salt-induced hypertension is associated with a
      reduction in levels of nitric oxide regardless of gender. Plasma prostaglandin E2
      and prostacyclin levels were higher in females. Taken together, the higher plasma
      prostaglandin levels and reduced sympathetic activity in females may be
      contributing factors in their lower blood pressure and reduced mortality.

PMID- 11339691
TI  - Examination of angiotensin II type 1 and type 2 receptor expression in human
      kidneys by immunohistochemistry.
AB  - Recent studies have suggested that both the angiotensin II type 1 (AT1) and type
      2 (AT2) receptors may be involved in the control of renal function in rodents.
      The aim of this study was to examine the distribution of these receptors in
      normal and diseased human kidneys. Kidney samples were obtained from 21 patients
      with and without glomerular lesions (3 control kidney samples from patients
      undergoing nephrectomy, 4 patients with minimal change disease, 6 patients with
      IgA nephropathy, and 8 patients with membranous glomerulonephritis). AT1 receptor
      immunohistochemical staining was examined and found to be most prominent in blood
      vessels, but staining of the tubules and glomeruli was also seen. In the case of
      the AT2 receptor, mild-moderate immunohistochemical staining was seen in the
      blood vessels, with weaker staining in the glomeruli. A similar distribution was
      seen in the patients with glomerulopathy. These results suggest that both AT1 and
      AT2 receptors are expressed in the normal human kidney, as well as in patients
      with glomerular disease. The histological distribution of these receptors
      supports the notion that both receptors may have a physiological role in normal
      and diseased kidneys in humans.

PMID- 11339692
TI  - Effect of nitric oxide inhibition on kidney function in experimental renovascular
      hypertension.
AB  - We examined the effect of acute systemic blockade of nitric oxide (NO) synthesis
      on blood pressure and renal function in rats with angiotensin II dependent two
      kidney, one-clip Goldblatt hypertension. Hypertensive animals had significantly
      higher blood pressures, plasma NO metabolite concentrations and urinary NO
      metabolite excretion rates than control rats. Intravenous administration of N(G)
      nitro-L-arginine methylester (L-NAME) (10 mg/kg) increased mean arterial pressure
      in both hypertensive and control animals with the magnitude of increase being
      greater in hypertensive than control rats (32 +/- 3 vs. 20 +/- 2 mmHg, p < 0.05).
      L-NAME did not affect glomerular filtration rates of normal and clipped kidneys
      but significantly decreased non-clipped kidney glomerular filtration rate (1.1 +/
      0.1 vs. 0.7 +/- 0.1 ml/min per g kidney wt, p < 0.05). Blood flow to normal and
      non-clipped kidneys fell in response to L-NAME. Percent reduction in renal blood
      flow produced by L-NAME was significantly greater in non-clipped than normal
      kidneys (38 +/- 3 vs. 24 +/- 2%, p < 0.05). In contrast, clipped kidney blood
      flow increased after L-NAME (3.3 +/- 0.2 vs. 4.0 +/- 0.2 ml/min per g kidney wt,
      p < 0.05). An identical improvement in clipped kidney blood flow occurred when
      arterial pressure was raised with aortic constriction indicating that the
      systemic pressor effect of L-NAME was responsible for this finding. These results
      indicate that NO plays an important role in systemic and non-clipped kidney
      hemodynamics in renovascular hypertension. Because NO has little influence on
      stenotic kidney function, the stimulus for increased NO system activity in this
      disease appears to be vascular shear stress rather than elevated circulating or
      intrarenal angiotensin II concentrations.

PMID- 11339693
TI  - Criteria and indicators of sustainable forest management.
AB  - Sustainable development is a term reflecting human, societal, and environmental
      values and in order to determine progress toward this goal; it is necessary to
      identify and define these values, and for governments or other institutions to
      establish the means to assess progress. Canada is directly involved in national
      and international processes to assess the sustainability of forest management
      processes using Criteria and Indicators. These consist of a group of broad core
      values (Criteria) and are supported by an number of measures (Indicators) to
      assess status or progress toward the realization of these values. Measuring and
      monitoring indicators is necessary to demonstrate progress toward sustainable
      development nationally and internationally. The criteria that have been
      identified include the traditional concepts of timber values, and include
      economics, environmental, social values, and national infrastructures. Each
      criterion is supported by a number of indicators to track progress. Countries in
      the international process also collaborate on defining terms, methods of
      reporting, and improving and enhancing indicators. C&I facilitate international
      reporting and provide a framework for international agreements while reflecting
      national differences in characteristics and descriptions of forests. The
      reporting process has stimulated the emergence of forest management issues that
      will influence forest science and forest ecosystem management in the future. For
      Canada, these include the development of a national system of forest ecosystem
      inventory, and ecological classification, the interpretation of the range of
      historic variation, and the adequacy and applicability of data sources.

PMID- 11339694
TI  - Canada's National Forest Inventory (responding to current information needs).
AB  - Canada's current National Forest Inventory is a periodic compilation of existing
      inventory material from across the country. While the current approach has many
      advantages, it lacks information on the nature and rate of changes to the
      resource, and does not permit projections or forecasts. Being a compilation of
      inventories of different dates, the current national forest inventory cannot
      reflect the current state of the forests and therefore cannot be used as a
      satisfactory baseline for monitoring change. The current format of Canada's
      National Forest Inventory has served its purpose by providing national
      statistical compilations and reporting. However, its useful life is coming to a
      conclusion. To meet new demands, Canada is considering a new National Forest
      Inventory design consisting of a plot-based system of permanent observational
      units located on a national grid. The objective of the new inventory design is to
      assess and monitor the extent, state and sustainability of Canada's forests in a
      timely and accurate manner. Details of the new inventory design are described. A
      strategy to respond to Canada's national and international forest reporting
      commitments through a National Forest Information System is also discussed.

PMID- 11339695
TI  - The Ontario forest health data co-operative.
AB  - The Canadian Forest Service, the Ontario Ministry of Natural Resources, and the
      Ontario Ministry of the Environment all conduct monitoring of forest health in
      Ontario. Among these agencies over 1500 permanent sample plots are monitored for
      purposes of assessing tree condition and/or site productivity. The data and
      length of record differ depending on the original intent of the plot system.
      However, a number of common variables are collected including basic tree
      measurements (tree height, stem diameter), mortality and site condition. Other
      variables collected at certain sites include crown condition, pest damage, ground
      vegetation, soils descriptions, and soils and foliage chemistry. A co-operative
      has been formed to compile this information from various sources and to make it
      more easily accessible. Information from these projects is available through the
      co-operative web site and can be extracted to report on forest health in a region
      of the province, or on an individual tree species. Information from these sources
      provide a picture of forest health in Ontario.

PMID- 11339696
TI  - An analysis of the daily radial activity of 7 boreal tree species, northwestern
      Quebec.
AB  - In the 'Des Vieux Arbres' ecological reserve situated within northwestern Quebec,
      40 band dendrometers were installed on 7 of the major boreal tree species. The
      late Spring-early Summer daily radial activity registered in 1997 was related to
      daily weather variables. For each tree species, the daily mean i) cumulative
      radial increment and ii) radial activity indexed series obtained by first
      difference standardization were analyzed. The results indicate the existence of
      strong similarities among the 7 species. All showed strong synchronous
      fluctuations in radius during late winter and early spring. This period ended
      with a short but sharp increase in radial increments that marked the passage of
      water into the stem. This initial swelling, less obvious in Pinus species was
      followed by a prolonged period of little change in radial activity.
      Meteorological data indicated that air temperature was positively related to stem
      swelling during the late winter-early spring period. Both air and soil
      temperatures became negatively related to radial expansion once the passage of
      water has occurred in the stem. Starting in early June, all species registered a
      sustained increase in radial increments possibly associated with active cell
      division. After this, radial expansion was negatively related to air temperature
      and positively to rainfall.

PMID- 11339697
TI  - Fluctuations of climatic conditions, elemental cycling and forest growth at the
      watershed scale.
AB  - The relationships between fluctuations in climatic conditions, forest
      productivity and elemental cycling were studied from 1994 to 1997 in a headwater
      catchment of the southern Laurentians dominated by sugar maple (Acer saccharum
      Marsh.) growing on podzolic soils. Annual budgets show that H+, K, and NO3 were
      retained in the watershed while Ca, Mg and Na were lost. The magnitude of the net
      annual budget for Ca, Mg and Na was correlated to annual variations in
      precipitation with the absolute budget value decreasing during dry years.
      Stemwood (r2 = 0.85) and total tree biomass production (r2 = 0.99) were
      correlated with mean annual temperature but fine roots and leaf litter were not.
      During the growing season, the pH of the organic horizons (FH) decreased as the
      volumetric water content of soil decreased. A positive association was also found
      between air temperature and H2O-soluble (r2 = 0.88) and PO4-extractable (r2 =
      0.99) SO4 in the upper B horizon. On a multiyear scale, we suspect that the
      decrease in the storage of inorganic SO4 in the soil results from the cumulative
      effects of annual variations in climatic conditions superimposed on the long-term
      decrease in SO4 deposition from the atmosphere. These soil changes were reflected
      by a decline in SO4, Ca and Mg concentrations in the stream. The generalisation
      of the observed short-term patterns to longer time scales must be approached with
      caution. Yet, our results indicate that the associations between climatic
      variations and the biogeochemistry of the ecosystem occur at different spatial
      and temporal scales and integrate a broad range of chemical components and
      ecosystem compartments. This reflects the inherent complexity of natural systems
      and offers a vast palette of indicators of the response of terrestrial ecosystems
      to variations in the intensity of environmental factors such as climatic
      conditions.

PMID- 11339698
TI  - Effects of regional reductions in sulphur deposition on the chemical and
      biological recovery of lakes within Killarney Park, Ontario, Canada.
AB  - The lakes in Killarney Provincial Park, located 40-60 km southwest of Sudbury,
      Ontario, were some of the first lakes in North America to be acidified by
      atmospheric pollutants. Acidification affected thousands of fish and invertebrate
      populations in dozens of lakes. Since the 1970's, water quality has improved in
      response to atmospheric pollution reductions and some lakes have already
      recovered to approximately their pre-industrial pH levels, as inferred from
      diatom microfossils in lake sediments. Since the 1970's, fish species richness
      has not changed substantially, but zooplankton species richness has increased in
      acidified lakes. The critical sulphur load, the amount of SO2-derived acid
      deposition that can occur while still maintaining suitable water quality, was
      estimated to be exceeded in 38% of the park area in 1997. Depending on which of
      four possible North American emission control scenarios (CLR = currently
      legislated reduction; CLR + 25%; CLR + 50%; CLR + 75%) is achieved by 2010, the
      projected critical loads will be exceeded in about 0-30% of the park area in the
      future. There are many factors that can affect biological recovery rates of
      damaged lakes, but it is expected that biological recovery will lag considerably
      behind observed chemical recovery rates.

PMID- 11339699
TI  - Monitoring the hydrology of Canadian prairie wetlands to detect the effects of
      climate change and land use changes.
AB  - There are millions of small isolated wetlands in the semi-arid Canadian prairies.
      These sloughs' are refuges for wildlife in an area that is otherwise intensively
      used for agriculture. They are particularly important as waterfowl habitat, with
      more than half of all North American ducks nesting in prairie sloughs. The water
      levels and ecology of the wetlands are sensitive to atmospheric change and to
      changes of agricultural practices in the surrounding fields. Monitoring of the
      hydrological conditions of the wetlands across the region is vital for detecting
      long-term trends and for studying the processes that control the water balance of
      the wetlands. Such monitoring therefore requires extensive regional-scale data
      complemented by intensive measurements at a few locations. At present, wetlands
      are being enumerated across the region once each year and year-round monitoring
      is being carried out at a few locations. The regional-scale data can be
      statistically related to regional climate data, but such analyses cast little
      light on the hydrological processes and have limited predictive value when
      climate and land use are changing. The intensive monitoring network has provided
      important insights but it now needs to be expanded and revised to meet new
      questions concerning the effects of climate change and land use.

PMID- 11339700
TI  - Linked hydrologic and climate variations in British Columbia and Yukon.
AB  - Climatic and hydrologic variations between the decades 1976-1985 and 1986-1995
      are examined at 34 climate stations and 275 hydrology stations. The variations in
      climate are distributed across a broad spatial area. Temperatures were generally
      warmer in the most recent decade, with many stations showing significant
      increases during the spring and fall. No significant decreases in temperature
      were found. Significant increases in temperature were more frequent in the south
      than in the northern portions of the region. Significant changes in precipitation
      were also more prevalent in the south. In coastal areas, there were significant
      decreases in precipitation during the dry season, and significant increases
      during the wet season. In the BC interior, significant precipitation decreases
      occurred during the fall, with significant increases during the winter and
      spring. In the north there were few changes in precipitation. The hydrologic
      responses to these variations in climate follow six distinctive patterns. The
      spatial distribution of these patterns suggests that in different ecozones, small
      variations in climate, particularly temperature, elicit different hydrologic
      responses.

PMID- 11339701
TI  - Mean annual temperature and total annual precipitation trends at Canadian
      biosphere reserves.
AB  - This article examines instrumental climate records from a variety of stations
      associated with the following Biosphere Reserves across Canada: (i) Waterton
      Lakes, (ii) Riding Mountain, (iii) Niagara Escarpment, (iv) Long Point, and (v)
      Kejimkujik (Candidate Biosphere Reserve). Annual series are generated from daily
      temperature and precipitation values. In addition, homogeneous data are used from
      other stations and regional records to supplement the records from the local
      biosphere stations. Long term trends are identified over the period of the
      instrumental record. In general, data from the interval 1900 to 1998 show cooler
      temperatures in the 1920's, warming from the early 1940's into the early 1950's,
      cooling into the 1970's, and subsequent warming. At many stations, 1998 is the
      warmest in the instrumental record. Comparisons with the regional data sets show
      good agreements between the temperature series. The 20th century warming is
      approximately 1.0 degree C in the Riding Mountain area and 0.6 degrees C in the
      Long Point, Niagara Escarpment, and Waterton Lakes areas. There has been slight
      cooling in the Kejimkujik area over the past half century. Precipitation data
      show increasing trends in the Kejimkujik. Long Point, Niagara Escarpment, and
      Waterton Lakes areas with no long term trend in the Riding Mountain area. This
      work is part of the Canadian Biosphere Reserves Association (CBRA) Climate Change
      Initiative (CCI), designed to present climate change information to Biosphere
      Reserve communities to allow local organizations to understand climate change and
      adapt to potential impacts.

PMID- 11339702
TI  - Modeling the hydroclimatic disturbance of soil landscapes in the southern
      Canadian plains: the problems of scale and place.
AB  - The sensitivity of soil landscapes to climatic variability and hydroclimatic
      events can be expressed as a landscape change safety factor, the ratio of
      potential disturbance to resistance to change. The use of a geographic
      information system (GIS) enables the spatially-explicit modeling of landscape
      sensitivity, but also raises the risk of violating the characteristic scales of
      disturbance and resistance, because the GIS technically simplifies the
      extrapolation of models, and associated concepts, to landscapes and scales not
      represented by the digital data base. Embedding landscape sensitivity into
      hierarchy theory, the formal analysis of the hierarchical structure of complex
      systems, provides a conceptual framework for the transfer of models and variables
      among landscape scales. In the subhumid southern Canadian plains, major
      hydroclimatic events (strong winds, intense rain, rapid snow melt) cause much of
      the physical disturbance of soil landscapes and terrestrial ecosystems. Prolonged
      dry or wet weather influences the resistance of soil and vegetation to these
      events. The potential disturbance of soil landscapes therefore can be derived
      from the probabilities of extreme events and seasonal conditions, as recorded in
      instrumental and proxy climate records. This time series analysis can be linked
      to the modeling of landscape sensitivity by establishing the probabilities of
      hydroclimatic events and climatic conditions which may exceed or lower the
      resistance of individual soil landscapes.

PMID- 11339703
TI  - Ecological Monitoring and Assessment Network's proposed core monitoring
      variables: an early warning of environmental change.
AB  - This article reports on the evaluation of existing ecological monitoring
      variables from a variety of sources to select a suite of core variables suitable
      for monitoring at the Ecological Monitoring and Assessment Network (EMAN) sites
      located across Canada. The purpose of EMAN is to promote the acquisition of
      relevant and consistent data that can be used to report on national trends and
      provide an early warning of ecosystem change. Existing monitoring variables were
      evaluated in two steps. In the first step, three primary criteria were used to
      pre-screen preliminary variables. In the second step, a more detailed evaluation
      considered twenty criteria based on data quality, applicability, data collection
      methods, data analysis and interpretation, existing data and programs, and cost
      effectiveness to select a draft set of core monitoring variables (CMV). An
      ecological framework was developed to organize the CMV in a manner that permitted
      a gap analysis to confirm the CMV assessed a wide range of relevant environment
      components. The suite of CMV were then tested to determine their effectiveness in
      detecting ecosystem change caused by stressors with ecosystem responses that have
      been well documented in the literature. This project is part of a process lead by
      Environment Canada to select CMV to detect and track ecosystem change at EMAN
      sites. It is anticipated that the proposed CMV will undergo future discussion and
      development leading to the final selection of a suite of CMV for use at EMAN
      sites.

PMID- 11339704
TI  - Monitoring long-term ecological changes through the Ecological Monitoring and
      Assessment Network: science-based and policy relevant.
AB  - Ecological monitoring and its associated research programs have often provided
      answers to various environmental management issues. In the face of changing
      environmental conditions, ecological monitoring provides decision-makers with
      reliable information as they grapple with maintaining a sustainable economy and
      healthy environment. The Ecological Monitoring and Assessment Network (EMAN) is a
      national ecological monitoring network consisting of (1) about 100 case study
      sites across the country characterized by long-term multi-disciplinary
      environmental work conducted by a multitude of agencies (142 partners and
      counting); (2) a variety of less comprehensive yet more extensive monitoring
      sites; (3) a network where core monitoring variables of ecosystem change are
      measured; and (4) geo-referenced environmental observations. Environment Canada
      is the co-ordinating partner for the network through the EMAN Co-ordinating
      Office. EMAN's mission is to focus a scientifically-sound, policy-relevant
      ecosystem monitoring and research network based on (a) stabilizing a network of
      case-study sites operated by a variety of partners, and (b) developing a number
      of cooperative dispersed monitoring initiatives in order to deliver unique and
      needed goods and services. These goods and services include: (1) an efficient and
      cost-effective early warning system which detects, describes and reports on
      changes in Canadian ecosystems at a national or ecozone scale; and (2) cross
      disciplinary and cross-jurisdictional assessments of ecosystem status, trends and
      processes. The early warning system and assessments of ecosystem status, trends
      and processes provide Environment Canada and partner organizations with timely
      information that facilitates increasingly adaptive policies and priority setting.
      Canadians are also informed of changes and trends occurring in Canadian
      ecosystems and, as a result, are better able to make decisions related to
      conservation and sustainability.

PMID- 11339705
TI  - The need for integrated linkages and long-term monitoring of mercury in Canada.
AB  - A nation-wide ecosystem science network for Canada was formed in 1994. At that
      time, mercury was a re-emerging issue in Canada and the Coordinating Office for
      the network sought collaboration to assess the issue. The key mechanisms by which
      the network has added value in addressing this issue are: 1) Information
      Dissemination, the network has organised, facilitated and co-hosted a number of
      regional. national and international mercury events (meetings, conferences and
      workshops) which have served to bring the expertise together, the network also
      disseminates information on it's web page. and the Coordinating Office hosts an
      annual National Science Conference: 2) Collaborative Mercury Monitoring, network
      partners advocated the need for a single hemispheric mercury network which
      resulted in the development of a compatible Canada-U.S. mercury deposition
      network, which may also be expanded into Mexico, and 3) Environmental Reporting,
      the network has collaborated with others to report on current mercury findings
      through initiatives such as the 1998 Northeast States and Eastern Canadian
      Mercury Study, a 1999 Mercury Case Study and is presently a partner in the
      University of Quebec's proposal to form a Collaborative Mercury Ecosystem
      Research Network in Canada.

PMID- 11339706
TI  - Use of water clarity to monitor the effects of climate change and other stressors
      on oligotrophic lakes.
AB  - We present evidence from studies of lakes in Killarney Park, Ontario, Canada that
      water clarity is a key variable for monitoring the effects of climate change,
      high UV exposure and acidification. In small oligotrophic lakes, these stressors
      affect water clarity primarily by altering the concentration of DOC in lake
      water. Clear lakes (<2 mg L(-1) DOC) proved to be highly sensitive indicators of
      stressors, exhibiting large thermal and optical responses to small changes in
      DOC. Extremely clear (<0.5 mg L(-1) DOC) acidic lakes showed the effects of
      climate change and solar bleaching in recent decades. These lakes became much
      clearer even though they were slowly recovering from acidification.

PMID- 11339707
TI  - Ecological change and the challenges for monitoring.
AB  - Anthropogenic activities are changing the chemical composition of the global
      atmosphere. This results in changes to the physical properties as well, such as
      the radiation balance. These properties are important input variables for
      biospheric processes. This paper discusses a number of documented ecological
      changes that have occurred in response to the changing atmosphere. Much of the
      information has been derived from data collected at integrated monitoring sites.
      The changing atmosphere is expected to result in many more ecological changes to
      resources of economic as well as environmental value. Defining and understanding
      these changes will be necessary for managing sustainable development and poses
      major challenges for monitoring programs in general and for integrated sites in
      particular.

PMID- 11339708
TI  - Ice storm damage and early recovery in an old-growth forest.
AB  - We quantified the damage caused by a major ice storm to individual trees in two 1
      ha permanent plots located at Mont St. Hilaire in southwestern Quebec, Canada.
      The storm, which occurred in January 1998, is the worst on record in eastern
      North America; glaze ice on the order of 80-100 mm accumulated at our study site.
      All but 3% of the trees (DBH > or = 10 cm) lost at least some crown branches, and
      35% lost more than half their crown. Damage to trees increased in the order:
      Tsuga canadensis, Betula alleghaniensis, Ostrya virginiana, Acer saccharum, Fagus
      grandifolia, Quercus rubra, Betula papyrifera, Acer rubrum, Tilia americana, and
      Fraxinus americana. Only 22% of the saplings and small trees (4 cm < DBH < 10 cm)
      escaped being broken or pinned to the ground by falling material. Levels of
      damage generally were greater in an exposed ridge top forest than in a cove
      protected from wind. By August 1999 only 53% of the trees had new shoots
      developing from the trunk or broken branches; among the more dominant canopy
      trees, Fagus grandifolia had the least sprouting and Acer saccharum and Quercus
      rubra the most. We anticipate and will monitor both significant turnover in the
      tree community and some shift in composition of the canopy dominants.

PMID- 11339709
TI  - Evaluation of the genotoxic potential of municipal waste water discharged into
      the Paraguay River during periods of flood and drought.
AB  - The cytogenotoxic effects of the waste water from Corumba and of the water of the
      Paraguay River, where this sewer discharges, were evaluated in flood and drought
      seasons. Allium cepa root meristems were exposed to 20 and 72 h treatments.
      Mitotic index, frequency, and types of aberrant cells were compared to the
      control. The waste water was genotoxic to this organism. The cycle of flood and
      drought influenced the levels of genotoxicity observed with the river water.

PMID- 11339710
TI  - Development of a free beta-galactosidase in vitro test for the assessment of
      heavy metal toxicity.
AB  - The effect of heavy metals and organic compounds on the activity of the enzyme
      beta-galactosidase in a standardized bioassay has been evaluated, considering
      future applications in environmental monitoring. The tests were done using a
      commercial extract of a hydrolase from the eukaryote yeast Kluyveromyces lactis
      and o-nitrophenyl-beta-D-galactopyranoside (ONPG) as substrate. The enzyme was
      exposed to Cr(VI), Cd(II), Cu(II), Ni(II), Pb(II), Hg(II), phenol, sodium dodecyl
      sulfate, methanol and pentachlorophenol for 5, 15, 30, and 60 min. According to
      the results, a 15 min exposure time was considered optimum for the performance of
      the assay. Results of tests with metals showed IC50 values ranging between
      9.25mg/L for Cd(II) and 0.015mg/L for Hg(II), with an order of sensitivity of:
      Cd(II) < Ni(II) < Cr(VI) = Pb(II) < Cu(II) < Hg(II). Sensitivity to organic
      compounds ranged from 200 to 4,000 mg/L, showing a higher specificity to heavy
      metals. The present in vitro free enzyme test showed a similar behavior to other
      tests based on beta-galactosidase such as the MetPlate. Furthermore, when
      compared to data from the literature on acute toxicity assays currently used in
      environmental assessment, test results show good agreement regarding the
      sensitivity to metals. After standardization, the proposed test could be used as
      a rapid and low-cost assay when evaluating biological effects of heavy metals in
      monitoring programs.

PMID- 11339711
TI  - Detection of nodularin in flounders and cod from the Baltic Sea.
AB  - The brackish water cyanobacterium Nodularia spumigena regularly forms waterblooms
      in the Baltic Sea. Many N. spumigena strains can produce nodularin, a hepatotoxic
      penta-peptide, which has caused several animal poisonings in the Baltic Sea area.
      To improve our understanding of nodularin bioaccumulation in aquatic organisms
      this study measured nodularin in flounder and cod caught from the Baltic Sea.
      Flounders were collected from the western Gulf of Finland in July 1996, September
      1997, and September 1998, and from the Gulf of Bothnia in August 1997 and
      September 1998. Flounders were also collected from the coastal areas of Sweden in
      the Baltic Proper during September 1998. Cod were caught from the southern Baltic
      Sea in August 1998. Livers and muscles of the 1997 fish were isolated, extracted,
      and analysed for nodularin using high-performance liquid chromatography (HPLC)
      and enzyme-linked immunosorbent assay (ELISA) and protein phosphatase 1 (PP1)
      inhibition assay. Approximately 30-70 ng of nodularin/g dry weight (maximum value
      140 ng/g) were found in the liver tissue samples by ELISA and PP1 inhibition.
      These concentrations were below the detection limit of HPLC. PP1 assay showed
      inhibition also in muscle samples, but this may due to other compounds present in
      the muscle extracts rather than NODLN or due to matrix interference. The recovery
      of nodularin from liver tissue with ELISA and PP1 assays was about 30%. Nodularin
      concentrations in samples are not corrected for recovery. Although the
      concentrations of nodularin found in this study are low further studies of
      nodularin are needed to assess possible bioaccumulation in brackish water food
      webs.

PMID- 11339712
TI  - Repeatability and reproducibility of the luminescent bacteria bioassay.
AB  - This paper presents the statistical analysis of the results of an inter
      laboratory study for the luminescent bacteria toxicity bioassay. It also contains
      a discussion on the statistical methods for the presentation and refinement of
      the evaluation of the precision of an assay method (including intra- and inter
      laboratory variability), with special emphasis on the rejection of outliers, and
      the use of standardized parameters, like the repeatability and reproducibility
      values.

PMID- 11339713
TI  - Toxicity evaluation of metal plating wastewater employing the Microtox assay: a
      comparison with cladocerans and fish.
AB  - The relative sensitivity of the Microtox assay is closely related to the type of
      toxicant, and hence its utility in biomonitoring effluents is better evaluated on
      a case-by-case basis. The Microtox assay, employing the marine bacterium Vibrio
      fischeri, was evaluated for its applicability in monitoring metal plating
      wastewater for toxicity. The results of the Microtox assay after 5, 15, and 30
      min of exposure, were compared with data obtained from conventional whole
      effluent toxicity testing (WET) methods that employed Daphnia magna, Ceriodaphnia
      dubia, and the fathead minnow (Pimephales promelas). The Microtox assay produced
      notably comparable EC50 values to the LC50 values of the acute fathead minnow
      toxicity test (< 0.5 order of difference). The Spearman's rank correlation
      analyses showed that the bacterial assay, regardless of exposure duration,
      correlated better with the acute fish than the daphnid results (p < 0.05). These
      observations were consistent to other studies conducted with inorganic
      contaminants. The relative sensitivity of the 30-min Microtox assay was within
      the range of the two frequently used acute daphnid/fish toxicity tests. In
      conclusion, the Microtox assay correlated well with the acute fathead minnow data
      and is well suited for toxicity monitoring for these types of industrial wastes.

PMID- 11339714
TI  - Acute toxicity of sodium selenate to two daphnids and three amphipods.
AB  - This study evaluated the acute toxicity of sodium selenate to two daphnid and
      three gammarid amphipod species. The daphnids, Ceriodaphnia dubia and Daphnia
      pulex, were evaluated in 48-hour static tests and the amphipods, Gammarus
      pseudolimnaeus, Gammarus lacustris, and Hyalella azteca, were evaluated in 96
      hour static and flow-through tests. Tests resulted in mean LC50's of 1.92, 9.12,
      1.82, 3.05, and 1.95 mg/L selenium for C. dubia, D. pulex, G. pseudolimnaeus, G.
      lacustris, and H. azteca, respectively. The LC50's for the G. pseudolimnaeus
      tests are more than 30-fold higher than previously reported LC50's for the same
      or similar species. The explanation for these differing results appears to be
      partially, but not entirely, explained by differences in ambient pH between the
      new studies and previous ones. Depending on how the new data are included in U.S.
      EPA's selenium freshwater quality criterion data set, the selenate acute water
      quality criterion (i.e., Criterion Maximum Concentration) increases from 12.8 to
      as high as 583 microg/L selenium.

PMID- 11339715
TI  - Assessment of toxicity and mutagenicity in air particulate matter from an urban
      industrial area in the coast of the Rio de la Plata.
AB  - Chemical characterization and effects assessment of semivolatile organic
      compounds in organic extracts from air particulate matter from the region of the
      greater La Plata area was undertaken. Effects covered the study of mutagenicity
      with the Ames test (Salmonella typhimurium TA100 and TA98 strains with metabolic
      activation by S9) and cytotoxicity using the Tetrahymena pyriformis test system
      (growth rate, cell volume, and cell respiration). Chemical analysis of organic
      extracts was done using gas chromatography. Results demonstrate the presence of
      polycyclic aromatic hydrocarbons (PAH) in the matrix, high mutagenicity, and
      cytotoxicity. A higher mutagenic activity detected with TA98 and TA100 strains is
      associated with an increment of total PAH and total five or six ring PAH content,
      respectively. Linked with it, a PAH dependent toxicity on Tetrahymena pyriformis
      has been observed. This cell system proved to be very sensitive. From the results
      obtained with the cell respiration assay with T. pyriformis it appears that
      uncoupling agents are present in the samples. The results of this study indicate
      that air particulate matter from the Rio de La Plata area contains significant
      genotoxic and cytotoxic activity probably due to the presence of PAHs.

PMID- 11339716
TI  - Interlaboratory study for the validation of an ecotoxicological procedure to
      monitor the quality of septic sludge received at a wastewater treatment plant.
AB  - Septic tank sludge is regularly hauled to the Montreal Urban Community (MUC)
      wastewater treatment plant. It is then discharged and mixed with the wastewater
      inflow before entering the primary chemical treatment process. An
      ecotoxicological procedure integrating chemical and toxicological analyses has
      been recently developed and applied to screen for the illicit discharge of toxic
      substances in septic sludge. The toxicity tests used were the Microtox, the
      bacterial-respiration, and the lettuce (Lactuca sativa) root elongation tests. In
      order to validate the applicability of the proposed procedure, a two-year
      interlaboratory study was carried out. In general, the results obtained by two
      independent laboratories (MUC and the Centre d'expertise en analyse
      environnementale du Quebec) were comparable and reproducible. Some differences
      were found using the Microtox test. Organic (e.g., phenol and formaldehyde) and
      inorganic (e.g., nickel and cyanide) spiked septic sludge were detected with good
      reliability and high efficiency. The relative efficiency to detect spiked
      substances was > 70% and confirms the results of previous studies. In addition,
      the respiration test was the most efficient toxicological tool to detect spiked
      substances, whereas the Microtox was the least efficient (< 15%). Efficiencies to
      detect spiked contaminants were also similar for both laboratories. These results
      support previous data presented earlier and contribute to the validation of the
      ecotoxicological procedure used by the MUC to screen toxicity in septic sludge.

PMID- 11339717
TI  - Silica sand as an artificial control sediment in a 20 day Neanthes
      arenaceodentata toxicity test.
AB  - The use of artificial control sediments in toxicity tests offers several
      advantages over field-collected control sediments, especially for laboratory
      cultured organisms such as Neanthes arenaceodentata. Ten side-by-side trials were
      conducted using a field-collected sediment from West Beach, Whidbey Island,
      Washington State, USA and an artificial sediment composed of a silica quartz sand
      commonly used for masonry applications. After a 20-d exposure to sediment and
      clean overlying seawater, a similar biological response (as measured by the final
      average individual dry weight of Neanthes) was observed. The average individual
      dry weight was 14.77 +/- 3.83 and 14.70 +/- 3.57 mg/worm for the artificial and
      field-collected negative controls, respectively.

PMID- 11339718
TI  - Application of the ethoxyresorufin-O-deethylase (EROD) assay to mixtures of
      halogenated aromatic compounds.
AB  - The ethoxyresorufin-O-deethylase (EROD) assay monitors the induction of the
      xenobiotic-metabolizing enzyme cytochrome P-450 (CYP) 1A1 and is a widely used
      biomarker for exposure of wildlife to substances that bind the aryl hydrocarbon
      (Ah) receptor. In this work the induction of EROD activity by single compounds
      and binary mixtures in primary rat hepatocytes was compared with the predictions
      of a kinetic model involving mixtures of inducers. The inducing agents were also
      examined for their ability to activate the Ah receptor to its DNA-binding form
      and for their ability to act as competitive inhibitors for CYP 1A1. Xenobiotics
      that failed to activate the Ah receptor did not induce EROD activity. Competitive
      inhibition for CYP 1A1 between the xenobiotic and 7-ethoxyresorufin caused EROD
      activity to fall at high xenobiotic concentrations. Competition for a limited
      number of Ah receptor sites depressed the EROD activity of a strong inducer such
      as 2,3,7,8-tetrachlorodibenzo-p-dioxin at high concentrations of a weak inducer.
      Application of the kinetic model to the example of a mixture of low
      concentrations of dibenzo-p-dioxins and much higher concentrations of
      polychlorinated biphenyls indicated that EROD assays often seriously
      underestimate the true potency of an environmental sample. Hence the EROD assay
      cannot be used for determining dioxin equivalent concentrations using the toxic
      equivalence factor approach.

PMID- 11339719
TI  - Assessment of the contaminant concentration variability among Lake Geneva Arctic
      char using stable isotopic composition (delta15N and delta13C).
AB  - Measurements of organochlorine [polychlorinated biphenyls (PCBs) and dichloro
      diphenyl-dichloroethylene (DDE)] and Hg concentrations and nitrogen and carbon
      stable isotopic compositions (delta15N and delta13C) were performed on 63 Arctic
      char (Salvelinus alpinus) from Lake Geneva. Fish exhibited a high interindividual
      variablity in pollutant concentrations. Since the accumulation of such persistent
      contaminants is obtained from food, the co-occurrence of dietary differentiation
      leading to the contaminant interindividual variability was suspected. delta15N
      and delta13C were used for assessing trophic position and food source differences
      among Arctic char. The low ranges of delta15N and delta13C could not explain the
      interindividual variability in pollutant concentrations. The lack of relation
      between delta15N and contaminant concentration did not suggest a trophic level
      biomagnification of PCB, DDE, and Hg. Lake Geneva spatial variability in
      pollutants may be an important factor of variability within the Arctic char
      population. The bioaccumulation pattern occurring for Hg was not apparent for PCB
      and DDE. Organochlorines are hydrophobic contaminants, and their bioaccumulation
      pattern may be masked by seasonal variations in fish lipid content.

PMID- 11339720
TI  - Preliminary evidence for in vivo tumour initiation by oral administration of
      extracts of the blue-green alga cylindrospermopsis raciborskii containing the
      toxin cylindrospermopsin.
AB  - New reports indicate that the toxic alkaloid cylindrospermopsin occurs in
      cyanobacteria in Israel, Florida, South America, and Australia in drinking water
      sources. This toxin is now recognised as a potential threat to human health.
      Furthermore, we have recently demonstrated the mutagenicity of cylindrospermopsin
      in vitro in a human lymphoblastoid cell-line. Therefore it is essential to
      determine whether cylindrospermopsin is also carcinogenic in vivo. In this
      preliminary study, 53 mice were treated up to three times orally with
      Cylindrospermopsis raciborskii extract containing cylindrospermopsin, while 27
      control mice were treated with saline. A proportion of each group were then given
      O-tetradecanoylphorbol 13-acetate (10 microg/mouse, twice weekly in liquid food)
      for the duration of the experiment; the remainder were given a control diet.
      After 30 weeks, the mice were euthanased and the major organs were examined
      histologically. Five tumours were found in 53 cylindrospermopsin-treated mice
      while none were found in the 27 controls. Although the number of animals used was
      too low to provide statistical significance (p=0.16), the calculated relative
      risk (RR=6.2; 95% CI: 0.33-117) indicates a potential biological and public
      health significance requiring further investigation. Estimates are given of the
      size of experiment required to provide statistical proof of cylindrospermopsin
      carcinogenicity.

PMID- 11339721
TI  - Measurement of pediatric illness severity using simple pretransport variables.
AB  - OBJECTIVE: To test the hypothesis that pretransport variables can predict in
      hospital mortality that will correlate with major interventions and unplanned
      events during interfacility transport. METHODS: A cohort of children (n = 2,253)
      transported by a specialized pediatric team to a children's hospital were
      studied. At the time of referral, data collected included age (months), heart
      rate, systolic blood pressure, respiratory rate, retractions, stridor or
      wheezing, seizures, skin perfusion, oxygen requirement, and mental status. Using
      univariate and stepwise logistic regression, variables predictive of in-hospital
      mortality were selected from a training set (n = 1,111) and assigned integers
      based on their computed coefficients. Probability of in-hospital mortality was
      calculated using the total integer score and age. The risk of mortality derived
      from the training set was validated in the remaining patients (n = 1,142) by
      comparing the observed and predicted mortalities. Major interventions performed
      and unplanned events were determined for each of five predetermined mortality
      risk groups. RESULTS: Variables (integers) predicting in-hospital mortality
      included systolic blood pressure (11), respiratory rate (6), oxygen requirement
      (11), and altered mental status (11). Observed mortality was similar to predicted
      mortality in all risk categories for the validation sample. As risk of mortality
      increased, so did the performance of major interventions and the occurrence of
      unplanned events. CONCLUSION: Four pretransport variables predicted in-hospital
      mortality. Risk of mortality correlated with the incidence of major patient
      interventions, and the occurrence of unplanned events increased as well. This
      model might be useful in comparing different transport systems using severity
      adjusted assessment of children requiring interfacility transport.

PMID- 11339722
TI  - Failed prehospital intubations: an analysis of emergency department courses and
      outcomes.
AB  - OBJECTIVE: To examine the reasons for failed prehospital endotracheal intubation
      (ETI) and to identify how the airway was subsequently managed in the emergency
      department (ED). METHODS: Data were collected from January to December 1998 for a
      county-wide paramedic system. Failed prehospital ETIs and perceived reasons for
      failure were identified. Subsequent ED airway management was reviewed. RESULTS:
      During the study period there were 13,112 patient contacts resulting in ETI
      attempts on 592 patients, of whom 536 (90.5%) were successfully intubated. Of the
      56 failed field intubations, 49 (87.5%) had ED charts available for review.
      Endotracheal intubation failure was associated with inadequate relaxation in 24
      (49%), difficult anatomy in ten (20%), and obstruction in five (10%). Successful
      ETI was achieved in the ED in 42 cases (86%). Twenty cases (41%) were facilitated
      by rapid-sequence intubation (RSI) in the ED. For those with incomplete
      relaxation in the field, 13 of 24 (54%) were intubated in the ED using RSI.
      Factors associated with the use of ED RSI include attempted prehospital
      nasotracheal intubation or attempted prehospital midazolam-facilitated intubation
      (p < 0.001). The predicted need for RSI in this prehospital system is
      approximately 3.9%. In eight cases, three or more ETI attempts or the use of
      rescue airways was required in the ED. The predicted minimum incidence of "truly
      difficult" intubation in this system is approximately 0.8-1.6%. CONCLUSIONS:
      Paramedic intubation failures result from a variety of factors. Less than half of
      field intubation failures were remedied in the ED by the use of neuromuscular
      blocking agents. A similar number were intubated without the use of RSI. A
      fraction of failed field ETIs may have resulted from inadequate operator training
      or experience. A small percentage of field patients were "truly difficult" and
      required advanced resources in the ED to facilitate airway management. Medical
      directors should be cognizant of the numerous factors affecting intubation
      performance when designing and implementing approaches to difficult prehospital
      airways.

PMID- 11339723
TI  - The use of etomidate for rapid-sequence intubation in the air medical setting.
AB  - OBJECTIVE: To describe the use of etomidate for rapid-sequence intubation (RSI)
      in the air medical environment. METHODS: This was a retrospective review of a
      consecutive series of patients receiving etomidate for RSI by a university
      hospital-based air medical program. Records of all patients more than 10 years of
      age requiring intubation during a 13-month period were reviewed. Data collected
      included demographics, site of intubation, person performing intubation,
      indication, diagnosis, medications administered, complications, and pre- and post

PMID- 11339724
TI  - Physician interpretation and quantitative measures of electrocardiographic
      ventricular fibrillation waveform.
AB  - OBJECTIVES: The characteristics of the ventricular fibrillation (VF) waveform may
      influence treatment decisions and the likelihood of therapeutic success. However,
      assessment of VF as being fine or coarse and the distinction between fine VF and
      asystole are largely subjective. The authors sought to determine the level of
      agreement among physicians for interpretation of varying VF waveforms, and to
      compare these subjective interpretations with quantitative measures. METHODS: Six
      second segments of waveform from LIFEPAK 300 units were collected. Fifty
      segments, including 45 VF and five ventricular tachycardia (VT) distracters, were
      graphed to simulate rhythm strips. These waveforms were quantitatively described
      using scaling exponent, root-mean-squared amplitude, and centroid frequency.
      Thirty-two emergency medicine residents were asked to interpret the arrhythmias
      as VT, "coarse" VF, "fine" VF, or asystole. Their responses were compared with
      the qantitative measures. Interphysician agreement was assessed with the kappa
      statistic. RESULTS: One thousand four hundred forty interpretations were
      analyzed. There was fair agreement between physicians about the classification of
      arrhythmias (kappa = 0.39). Mean values associated with coarse VF, fine VF, and
      asystole differed in all three quantitative measure categories. The decision
      whether to defibrillate was highly correlated with the distinction between VF and
      asystole (Pearson chi-square = 1,170.40, df = 1, p[two-sided] < 0.001).
      CONCLUSIONS: With only fair agreement on the threshold of fine VF and asystole,
      defibrillation decisions are largely subjective and caregiver-specific. These
      data suggest that quantitative measures of the VF waveform could augment the
      current standard of subjective classification of VF by emergency care providers.

PMID- 11339726
TI  - Time saved with the use of emergency warning lights and siren while responding to
      requests for emergency medical aid in a rural environment.
AB  - OBJECTIVE: To determine whether the use of warning lights and siren saves a
      significant amount of time for ambulances responding to requests for emergency
      medical aid in a rural emergency medical services (EMS) setting. METHODS: A
      prospective design was used to determine run times for ambulances responding to
      calls with lights and siren (code 3) and for a similarly equipped "chase"
      ambulance traveling to the same destination via the same route without lights and
      siren, while obeying all traffic laws (code 2) within a rural setting. Data were
      collected for run time intervals, distance traveled, visibility, road surface
      conditions, time of day, and day of the week. Descriptive statistics, a paired
      Student's t-test, and analysis of variance were used to test for significant
      differences between code 2 and code 3 operations, as well as the other variables
      listed above. RESULTS: Sixty-seven runs were timed during a 21-month period. The
      average code 3 response interval was 8.51 minutes. The average code 2 response
      interval was 12.14 minutes. The 3.63 minutes saved on average represents
      significant time savings of 30.9% (p < 0.01). Shorter runs had higher time
      savings per mile than the longer runs. Run distance was the only variable that
      was statistically significant in affecting time saved during a code 3 response.
      CONCLUSION: Code 3 operation by EMS personnel in a rural EMS setting saved
      significant time over code 2 operation when traveling to a call.

PMID- 11339725
TI  - Paramedic use of endotracheal tube introducers for the difficult airway.
AB  - OBJECTIVE: To evaluate the ability of paramedics to learn and apply the skill of
      introducer-aided oral intubation in the setting of the simulated "difficult
      airway." The authors hypothesized that, following a brief introduction to the
      device, intubation success rates would not differ for traditional and introducer
      aided intubations of an immobilized airway mannequin. METHODS: During a paramedic
      recertification class, experienced paramedics were given a brief didactic
      introduction to the "bougie-like" Flex Guide endotracheal tube introducer (ETTI).
      The participants were then asked to intubate adult mannequins immobilized in the
      head-neutral position, with and without the ETTI. "Successful placement" was
      defined as completion of the procedure within 30 seconds and endotracheal tube
      position confirmed by the investigator with direct visualization. RESULTS: For
      both traditional and ETTI intubations, 34 (97%) of the 35 paramedics successfully
      intubated within 30 seconds. The two unsuccessful intubation attempts were
      recognized by the paramedic as esophageal intubations, and correct tube placement
      was obtained within an additional 30 seconds. CONCLUSION: In this study, use of
      the ETTI was mastered by the participants after only a brief didactic
      introduction to the device, with their ability to intubate an immobilized
      mannequin using the ETTI being equal to their ability to perform traditional
      intubation. These results suggest that use of the ETTI is easily learned, and may
      support the device's role in the prehospital management of the difficult airway.

PMID- 11339727
TI  - The use of midazolam for prehospital rapid-sequence intubation may be associated
      with a dose-related increase in hypotension.
AB  - OBJECTIVE: To investigate the incidence of hypotension associated with the use of
      midazolam for prehospital rapid-sequence intubation (RSI). METHODS: A
      retrospective review was performed using charts from the two aeromedical agencies
      servicing the authors' region. The RSI protocols used by crews from the northern
      (north) and the southern (south) parts of the region were identical, with the
      exception of midazolam dosing. The north crews used 0.1 mg/kg for all patients,
      while the south crews used 0.1 mg/kg up to a maximum of 5 mg. All patients
      receiving midazolam for prehospital RSI were pooled, with multiple linear
      regression used to investigate the relationship between midazolam dose and both
      hypotension and a decrease in systolic blood pressure (SBP) following RSI.
      Patients weighing >50 kg and patients with traumatic brain injury (TBI) were
      evaluated separately to determine differences between north and south with regard
      to midazolam dosing and incidence of hypotension. Multivariate logistical
      regression was used to test for these differences and for potential confounders
      such as age, initial SBP, and Glasgow Coma Scale score (GCS). RESULTS: A total of
      219 patients were identified from the north (n = 75) and the south (n = 144).
      Multiple linear regression revealed a statistically significant relationship
      between midazolam dose and both hypotension and an SBP decrease following RSI.
      There was no difference between north and south with regard to age, sex,
      incidence of TBI, initial SBP, or GCS. In patients >50 kg, those from the north
      received higher doses of midazolam and had a higher incidence of hypotension than
      those from the south. This relationship was also present in 184 patients with
      TBI. CONCLUSION: The use of midazolam with prehospital RSI is associated with a
      dose-related incidence of hypotension.

PMID- 11339728
TI  - Emergency medical services equipment hygiene practices.
AB  - OBJECTIVE: To determine whether emergency medical services (EMS) systems adhere
      to accepted equipment hygiene standards. METHODS: Mail surveys were sent to the
      physician medical directors of the EMS systems of the 125 most populous cities in
      the United States. RESULTS: Eighty-five surveys (68%) were returned. Seventy
      three (86%) of the responding services have a policy addressing equipment
      decontamination, and 32 of these (44%) have an accompanying quality assurance
      program. Seventy-nine (93%) utilize either alcohol or a commercial disinfectant
      (A/CD) on noncritical items when visibly contaminated with blood. However, only
      32 of those agencies (41%) use soap and water in addition to A/CD. Another nine
      (11%) exchange contaminated items at the hospital, one (1%) uses other methods,
      and two (2%) respondents did not know. Seventy-six (89%) of the responding
      agencies perform endotracheal intubation. Of the 54 that decontaminate their own
      blades, 20 (37%) use soap and water in addition to A/CD, 32 (59%) use A/CD alone,
      and two (4%) use soap and water alone. CONCLUSION: Adherence to accepted hygiene
      standards among EMS systems in our most populous cities is poor. Many systems do
      not use soap and water prior to A/CD. Failure to do so may minimize the
      effectiveness of disinfection. Several systems use A/CD or soap and water alone,
      neither of which meets current standards for high-level disinfection recommended
      for items that will come in contact with mucous membranes, such as laryngoscope
      blades.

PMID- 11339729
TI  - Emergency medical services telephone referral program: an alternative approach to
      nonurgent 911 calls.
AB  - OBJECTIVE: To examine the effects of transferring nonurgent 911 calls to a
      telephone consulting nurse. It was hypothesized that the telephone referral
      program would result in fewer basic life support (BLS) responses with no adverse
      patient outcome or decrease in patient satisfaction. METHODS: A two-phased
      prospective study was conducted in an urban and rural setting with a population
      of 650,000. During phase I, a BLS unit was dispatched on all calls and a nurse
      intervention was simulated. During phase II, no BLS unit was dispatched for calls
      meeting study criteria. Callers were transferred to the nurse, and consulting
      nurse protocols were used to direct care. Data were collected from dispatch, BLS,
      nurse, and hospital records and patient self-assessment. RESULTS: During phase I,
      38 callers were transferred to the consulting nurse with no nurse intervention.
      During phase II, 133 cases were transferred to the nurse line. There were no
      adverse outcomes detected. The nurse recommended home care for 31%, physician
      referral for 24%, referral back to 911 for 17%, community resource for 11%, and
      other referral for 17%. Nurses contacted 85 patients for telephone follow-up.
      Ninety-four percent of the patients reported feeling better, 6% felt the same,
      and none felt worse. Patients were satisfied with the outcome in 96% of the
      cases. CONCLUSION: Transferring 911 calls to a nurse line resulted in fewer BLS
      responses and no adverse patient outcomes, while maintaining high patient
      satisfaction. Dispatch criteria correctly identified cases with minimal medical
      needs. A high percentage of the patients reported feeling better after the
      intervention. This study has major implications for communities interested in
      efficient use of emergency medical services resources.

PMID- 11339730
TI  - Training prehospital personnel in saphenous vein cutdown and adult intraosseous
      access techniques.
AB  - OBJECTIVE: To compare the success rates, complication rates, and times required
      for paramedic students to perform saphenous vein cutdown and adult intraosseous
      infusion using the bone injection gun (BIG). METHODS: This was a prospective,
      randomized crossover study of 13 senior-level students in a baccalaureate degree
      paramedic program. Study subjects were instructed in adult intraosseous and
      saphenous vein cutdown techniques through lecture and laboratory exercises and
      then randomized into two groups. Group 1 performed saphenous vein cutdown at the
      ankle, followed by intraosseous infusion using the BIG. Group 2 performed the
      same procedures but in reverse order. All procedures were performed on preserved
      cadavers and videotaped. Using a standardized scoring sheet, the authors
      evaluated the study subjects at the time of the procedures to determine success
      rates, errors, and complications. Videotapes were later reviewed to verify the
      time required to complete the procedures. RESULTS: The normalized mean procedure
      scores were 96.15 (SD 4.28) and 83.83 (SD 15.52) for the intraosseous infusion
      and saphenous vein cutdown procedures, respectively (95% CI for difference in
      means, -12.34 to -1.3; p = 0.020). Success rates for establishing venous access
      were higher for the intraosseous route (92.3%) than the cutdown technique
      (69.2%), but did not achieve statistical significance (p = 0.250). The times
      required to initiate fluid flow were 3.91 minutes (SD 0.82) by the intraosseous
      route and 7.57 minutes (SD 1.80) by venous cutdown (95% CI for difference in
      means, 2.43 to 5.55; p = 0.000). One critical error and 11 noncritical errors
      were encountered during the intraosseous procedure, compared with ten critical
      errors and 29 noncritical errors during the cutdown procedure ( p = 0.195).
      CONCLUSION: In a group of inexperienced paramedic students working on a preserved
      human cadaver model, intravenous access was gained more rapidly, with a higher
      success rate, and with fewer complications using the bone injection gun than by
      the saphenous vein cutdown procedure. Further study is needed to evaluate these
      procedures in the field setting and to compare their feasibility with other
      alternative venous access techniques such as femoral, external jugular, and
      central venous cannulation.

PMID- 11339731
TI  - Prehospital use of continuous positive airway pressure (CPAP) for presumed
      pulmonary edema: a preliminary case series.
AB  - OBJECTIVE: To describe the prehospital use of a continuous positive airway
      pressure (CPAP) system for the treatment of acute respiratory failure presumed to
      be due to cardiogenic pulmonary edema. METHODS: Prospective case-series analysis.
      Paramedics administered CPAP via face mask at 10 cm H2O to patients believed to
      be in cardiogenic pulmonary edema and in imminent need of endotracheal intubation
      (ETI). Data from run sheets and hospital records were analyzed for treatment
      intervals, vital signs, complications, admitting diagnoses, need for ETI, and
      mortality. RESULTS: Nineteen patients received prehospital CPAP therapy. Mean
      duration of therapy was 15.5 minutes. Pre- and post-therapy pulse oximetry was
      available for 15 patients and demonstrated an increase from a mean of 83.3% to a
      mean of 95.4%. None of the patients were intubated in the field. Two patients who
      did not tolerate the CPAP mask required ETI upon arrival in the emergency
      department (ED); an additional five patients required ETI within 24 hours. There
      was one death in the series and two additional adverse events (one aspiration
      pneumonia, one pneumothorax); none of these were attributable to the use of CPAP.
      The diagnosis of cardiogenic pulmonary edema was corroborated by the ED or in
      hospital physician in 13 patients (68%). Paramedics reported no technical
      difficulties with the CPAP system. CONCLUSION: For patients with acute
      respiratory failure and presumed pulmonary edema, the prehospital use of CPAP is
      feasible and may avert the need for ETI. Future controlled studies are needed to
      assess the utility and cost-effectiveness of prehospital CPAP systems.

PMID- 11339732
TI  - A two-hour intervention using START improves prehospital triage of mass casualty
      incidents.
AB  - OBJECTIVE: There are few data concerning the ability of prehospital providers to
      triage patients in a mass casualty incident (MCI). The authors evaluated the
      effectiveness of a brief educational intervention on MCI triage with a written
      scenario and test. The START method (simple triage and rapid treatment) was used.
      METHODS: The authors enrolled and tested 109 prehospital providers consisting of
      31 paramedics and prehospital registered nurses (PHRNs) and 78 emergency medical
      technicians (EMTs) and first responders. A written scenario of an MCI was used to
      test participants before, immediately after, and again at one month after a two
      hour educational intervention consisting of a slide and video presentation
      utilizing START. RESULTS: The 109 participants completed the pre-intervention and
      post-intervention test; 72 (66%) completed the one-month post-intervention as
      well. Mean work experience was 9 years (ranging from 1 to 27 years). The mean
      immediate post-test score (75% correct) was significantly improved compared with
      the mean pretest score (55% correct) for the 109 providers completing both tests
      (p < 0.001). Among advanced life support providers (EMT-Ps and PHRNs) completing
      all three surveys, the mean immediate post-test score (76% correct) and mean one
      month post-test score (75% correct) were not significantly different. Among the
      basic life support providers completing all three surveys, a modest but
      statistically significant decay in mean scores from immediate post-test (74%
      correct) to one-month post-test (68% correct) was observed (p < 0.01). Prior
      training in MCI had no statistically significant effect on changes in mean test
      scores. CONCLUSION: The ability of prehospital providers of all levels of
      training and experience to triage patients in an MCI is less than optimal.
      However, this ability improved dramatically after a single didactic session, and
      improvement persisted one month later.

PMID- 11339733
TI  - Subcutaneous epinephrine in the prehospital setting.
AB  - OBJECTIVES: To outline current practice regarding the prehospital use of
      subcutaneous epinephrine, and systematically review the existing literature to
      determine the level of support for its use in the elderly. Many health care
      personnel are reluctant to administer subcutaneous epinephrine for potentially
      life-threatening conditions such as asthma and anaphylaxis in older patients.
      This sytematic review examined the following focused question: "For older
      patients not known to have coronary artery disease, does administration of
      subcutaneous epinephrine carry a significant enough risk of cardiovascular side
      effects to mandate age as a relative contraindication to self-administration or
      emergency medical services administration in the prehospital setting?" METHODS:
      The MEDLINE and Health Star databases were searched to identify studies
      evaluating the use of subcutaneous epinephrine in the treatment of asthma and
      anaphylaxis. Bibliographies from included studies, known reviews, and textbooks
      were examined to identify additional studies. The strength of evidence presented
      in each study was assessed in accordance with the classification system proposed
      by the American Heart Association's Emergency Cardiovascular Care Committee.
      RESULTS: The review of the literature revealed only three case reports (level VII
      evidence) that record adverse reactions of epinephrine when used for anaphylaxis
      and allergy, while several level III and V studies found no adverse effects when
      used for asthma. No controlled trials documenting adverse effects were found.
      CONCLUSIONS: The authors did not find significant evidence to contraindicate the
      use of subcutaneous epinephrine in older patients who are not known to have
      coronary artery disease, who present with either asthma or allergic reactions.

PMID- 11339734
TI  - End-tidal carbon dioxide monitoring in the prehospital setting.
AB  - End-tidal carbon dioxide (ETCO2) monitoring is an exciting technology and has the
      potential to become a very useful tool in the prehospital setting. It can be
      useful in verifying endotracheal tube position and during cardiopulmonary
      resuscitation in the field. Recent reports of misplaced endotracheal tubes in the
      prehospital setting make it important to ensure that paramedics learn correct
      techniques of endotracheal intubation, and that they verify tube placement with
      an ETCO2 monitor. 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 terminology, the
      basic physiology, the technology (both colorimetric detectors and infrared
      capnometers), and the clinical applications of ETCO2 monitoring with special
      reference to the pediatric patient.

PMID- 11339735
TI  - Agitated delirium and sudden death: two case reports.

PMID- 11339736
TI  - Engineering is preferred over physics as an undergraduate preparation for
      diagnostic and nuclear medical physicists.

PMID- 11339737
TI  - Spatial resolution measurements in quasimonochromatic x rays with mosaic crystals
      for mammography application.
AB  - A novel x-ray source for mammography application is being investigated.
      Quasimonochromatic x rays have been produced via Bragg diffraction with a W-anode
      x-ray tube and a graphite mosaic crystal array. The system provides 18 keV x rays
      with an energy resolution deltaE/E approximately equals 0.12. A thorough analysis
      of the spatial resolution of the system has been performed in order to understand
      and quantify the effect of the introduction of an active optical element such as
      a mosaic crystal in the x-ray path. The focal spot of the source and its emission
      properties have been studied by using the slit camera method. Experiments have
      shown that the introduction of a mosaic crystal in the optical path modifies the
      resolution properties of the Bragg diffraction-based radiography system. Along
      the direction perpendicular to the diffraction plane the resolution properties of
      the imaging system mainly depend on the x-ray tube focal spot size and position.
      Along the diffraction plane the focal spot size depends on mosaic characteristics
      and on the geometrical setup. Hence, it could be modified by setting the
      appropriate experimental conditions.

PMID- 11339738
TI  - Human observer detection experiments with mammograms and power-law noise.
AB  - We determined contrast thresholds for lesion detection as a function of lesion
      size in both mammograms and filtered noise backgrounds with the same average
      power spectrum, P(f)=B/f3. Experiments were done using hybrid images with digital
      images of tumors added to digitized normal backgrounds, displayed on a monochrome
      monitor. Four tumors were extracted from digitized specimen radiographs. The
      lesion sizes were varied by digital rescaling to cover the range from 0.5 to 16
      mm. Amplitudes were varied to determine the value required for 92% correct
      detection in two-alternative forced-choice (2AFC) and 90% for search experiments.
      Three observers participated, two physicists and a radiologist. The 2AFC
      mammographic results demonstrated a novel contrast-detail (CD) diagram with
      threshold amplitudes that increased steadily (with slope of 0.3) with increasing
      size for lesions larger than 1 mm. The slopes for prewhitening model observers
      were about 0.4. Human efficiency relative to these models was as high as 90%. The
      CD diagram slopes for the 2AFC experiments with filtered noise were 0.44 for
      humans and 0.5 for models. Human efficiency relative to the ideal observer was
      about 40%. The difference in efficiencies for the two types of backgrounds
      indicates that breast structure cannot be considered to be pure random noise for
      2AFC experiments. Instead, 2AFC human detection with mammographic backgrounds is
      limited by a combination of noise and deterministic masking effects. The search
      experiments also gave thresholds that increased with lesion size. However, there
      was no difference in human results for mammographic and filtered noise
      backgrounds, suggesting that breast structure can be considered to be pure random
      noise for this task. Our conclusion is that, in spite of the fact that
      mammographic backgrounds have nonstationary statistics, models based on
      statistical decision theory can still be applied successfully to estimate human
      performance.

PMID- 11339739
TI  - Field nonuniformity correction for quantitative analysis of digitized mammograms.
AB  - Several factors, including the heel effect, variation in distance from the x-ray
      source to points in the image and path obliquity contribute to the signal
      nonuniformity of mammograms. To best use digitized mammograms for quantitative
      image analysis, these field non-uniformities must be corrected. An empirically
      based correction method, which uses a bowl-shaped calibration phantom, has been
      developed. Due to the annular spherical shape of the phantom, its attenuation is
      constant over the entire image. Remaining nonuniformities are due only to the
      heel and inverse square effects as well as the variable path through the beam
      filter, compression plate and image receptor. In logarithmic space, a normalized
      image of the phantom can be added to mammograms to correct for these effects.
      Then, an analytical correction for path obliquity in the breast can be applied to
      the images. It was found that the correction causes the errors associated with
      field nonuniformity to be reduced from 14% to 2% for a 4 cm block of material
      corresponding to a combination of 50% fibroglandular and 50% fatty breast tissue.
      A repeatability study has been conducted to show that in regions as far as 20 cm
      away from the chest wall, variations due to imaging conditions and phantom
      alignment contribute to <2% of overall corrected signal.

PMID- 11339740
TI  - A controlled phantom study of a noise equalization algorithm for detecting
      microcalcifications in digital mammograms.
AB  - We report on some extensions and further developments of a well-known
      microcalcification detection algorithm based on adaptive noise equalization.
      Tissue equivalent phantom images with and without labeled microcalcifications
      were subjected to this algorithm, and analyses of results revealed some
      shortcomings in the approach. Particularly, it was observed that the method of
      estimating the width of distributions in the feature space was based on
      assumptions which resulted in the loss of similarity preservation
      characteristics. A modification involving a change of estimator statistic was
      made, and the modified approach was tested on the same phantom images. Other
      modifications for improving detectability such as downsampling and use of
      alternate local contrast filters were also tested. The results indicate that
      these modifications yield improvements in detectability, while extending the
      generality of the approach. Extensions to real mammograms and further directions
      of research are discussed.

PMID- 11339741
TI  - Knowledge-based computer-aided detection of masses on digitized mammograms: a
      preliminary assessment.
AB  - The purpose of this work was to develop and evaluate a computer-aided detection
      (CAD) scheme for the improvement of mass identification on digitized mammograms
      using a knowledge-based approach. Three hundred pathologically verified masses
      and 300 negative, but suspicious, regions, as initially identified by a rule
      based CAD scheme, were randomly selected from a large clinical database for
      development purposes. In addition, 500 different positive and 500 negative
      regions were used to test the scheme. This suspicious region pruning scheme
      includes a learning process to establish a knowledge base that is then used to
      determine whether a previously identified suspicious region is likely to depict a
      true mass. This is accomplished by quantitatively characterizing the set of known
      masses, measuring "similarity" between a suspicious region and a "known" mass,
      then deriving a composite "likelihood" measure based on all "known" masses to
      determine the state of the suspicious region. To assess the performance of this
      method, receiver-operating characteristic (ROC) analyses were employed. Using a
      leave-one-out validation method with the development set of 600 regions, the
      knowledge-based CAD scheme achieved an area under the ROC curve of 0.83. Fifty
      one percent of the previously identified false-positive regions were eliminated,
      while maintaining 90% sensitivity. During testing of the 1,000 independent
      regions, an area under the ROC curve as high as 0.80 was achieved. Knowledge
      based approaches can yield a significant reduction in false-positive detections
      while maintaining reasonable sensitivity. This approach has the potential of
      improving the performance of other rule-based CAD schemes.

PMID- 11339742
TI  - A new algorithm for computer tomographic reconstruction from partial view
      projections.
AB  - Conventional algorithms for tomographic reconstruction require the acquisition of
      a complete set of projections at uniform angular displacements. In many cases,
      however, the geometry of the sample or a loss of data can significantly reduce
      the range of the available projections. Several algorithms have been proposed in
      literature to handle such situations, but their performances are low or they
      require strong constraints and hypothesis about the nature of the sample or the
      data. Here a new method is proposed. It is based on a novel morphing technique,
      which affords in general terms the problem of curve matching and is here
      specialized to the case of tomographic reconstruction. The proposed algorithm is
      very fast in comparison to other approaches having similar effectiveness;
      furthermore, it allows one to obtain good quality images even when a significant
      fraction of the views is absent, without any hypothesis about the nature of the
      sample or the kind of measurement. The results obtained by applying this
      technique to the Shepp-Logan phantom and to a clinical scan are reported here and
      discussed.

PMID- 11339743
TI  - Effect of scattered radiation on image noise in cone beam CT.
AB  - Cone beam CT has a capability for the 3-dimensional imaging of large volumes with
      isotropic resolution, and has a potentiality for 4-dimensional imaging (dynamic
      volume imaging), because cone beam CT acquires data of a large volume with one
      rotation of an x-ray tube-detector pair. However, one of the potential drawbacks
      of cone beam CT is a larger amount of scattered x-rays, which may enhance the
      noise in reconstructed images, and thus affect the low-contrast detectablity. Our
      aim in this work was to estimate the scatter fractions and effects of scatter on
      image noise, and to seek methods of improving image quality in cone beam CT.
      First we derived a relationship between the noise in a reconstructed image and in
      an x-ray intensity measurement. Then we estimated the scatter to primary ratios
      in x-ray measurements using a Monte-Carlo simulation. From these we estimated the
      image noise under relevant clinical conditions. The results showed that the
      scattered radiation made a substantial contribution to the image noise. However,
      focused collimators could improve it by decreasing the scattered radiation
      drastically while keeping the primary radiation at nearly the same level. A
      conventional grid also improved the image noise, though the improvement was less
      than that of focused collimators.

PMID- 11339744
TI  - Generalized multi-dimensional adaptive filtering for conventional and spiral
      single-slice, multi-slice, and cone-beam CT.
AB  - In modern computed tomography (CT) there is a strong desire to reduce patient
      dose and/or to improve image quality by increasing spatial resolution and
      decreasing image noise. These are conflicting demands since increasing resolution
      at a constant noise level or decreasing noise at a constant resolution level
      implies a higher demand on x-ray power and an increase of patient dose. X-ray
      tube power is limited due to technical reasons. We therefore developed a
      generalized multi-dimensional adaptive filtering approach that applies nonlinear
      filters in up to three dimensions in the raw data domain. This new method differs
      from approaches in the literature since our nonlinear filters are applied not
      only in the detector row direction but also in the view and in the z-direction.
      This true three-dimensional filtering improves the quantum statistics of a
      measured projection value proportional to the third power of the filter size.
      Resolution tradeoffs are shared among these three dimensions and thus are
      considerably smaller as compared to one-dimensional smoothing approaches. Patient
      data of spiral and sequential single- and multi-slice CT scans as well as
      simulated spiral cone-beam data were processed to evaluate these new approaches.
      Image quality was assessed by evaluation of difference images, by measuring the
      image noise and the noise reduction, and by calculating the image resolution
      using point spread functions. The use of generalized adaptive filters helps to
      reduce image noise or, alternatively, patient dose. Image noise structures,
      typically along the direction of the highest attenuation, are effectively
      reduced. Noise reduction values of typically 30%-60% can be achieved in
      noncylindrical body regions like the shoulder. The loss in image resolution
      remains below 5% for all cases. In addition, the new method has a great potential
      to reduce metal artifacts, e.g., in the hip region.

PMID- 11339745
TI  - Investigation of the slice sensitivity profile for step-and-shoot mode multi
      slice computed tomography.
AB  - Multislice compound tomography (MCT) is one of the recent technology advancements
      in CT. Compared to single slice CT, MCT significantly improves examination time,
      x-ray tube efficiency, and contrast material utilization. Although the scan mode
      of MCT is predominately helical, step-and-shoot (axial) scans continue to be an
      important part of routine clinical protocols. In this paper, we present a
      detailed investigation on the slice sensitivity profile (SSP) of MCT in the step
      and-shoot mode. Our investigation shows that, unlike single slice CT, the SSP for
      MCT exhibits multiple peaks and valleys resulting from intercell gaps between
      detector rows. To fully understand the characteristics of the SSP, we developed
      an analytical model to predict the behavior of MCT. We propose a simple
      experimental technique that can quickly and accurately measure SSP. The impact of
      the SSP on image artifacts and low contrast detectability is also investigated.

PMID- 11339746
TI  - Cascade analysis for medical imaging detectors with stages involving both
      amplification and dislocation processes.
AB  - Cascade analysis is a powerful tool which can be used to calculate the signal and
      noise properties of medical imaging detectors. It involves the conceptual
      separation of the imaging chain into stages which consist of either pure
      amplification or pure dislocation stages. It is, however, not always possible to
      break the physical processes down to these elementary stages. In this work we
      derive a new cascade equation which is applicable to any stage which involves
      multiple amplifications and dislocations. The equation simplifies to the known
      equations for pure amplification and pure dislocation stages in the appropriate
      limits, and can be numerically calculated using Monte Carlo techniques for more
      complicated situations. We demonstrate the use of this equation with an example:
      we derive an expression for the DQE of a metal/phosphor detector for megavoltage
      imaging with our formalism, and evaluate the expression with Monte Carlo
      techniques. We have found that there is excellent agreement between theory and
      experimental results, and believe that the formalism could be useful for other
      applications where the amplification and dislocation processes cannot be divided
      into elementary stages.

PMID- 11339747
TI  - Artificial neural network Radon inversion for image reconstruction.
AB  - Image reconstruction techniques are essential to computer tomography. Algorithms
      such as filtered backprojection (FBP) or algebraic techniques are most frequently
      used. This paper presents an attempt to apply a feed-forward back-propagation
      supervised artificial neural network (BPN) to tomographic image reconstruction,
      specifically to positron emission tomography (PET). The main result is that the
      network trained with Gaussian test images proved to be successful at
      reconstructing images from projection sets derived from arbitrary objects.
      Additional results relate to the design of the network and the full width at half
      maximum (FWHM) of the Gaussians in the training sets. First, the optimal number
      of nodes in the middle layer is about an order of magnitude less than the number
      of input or output nodes. Second, the number of iterations required to achieve a
      required training set tolerance appeared to decrease exponentially with the
      number of nodes in the middle layer. Finally, for training sets containing
      Gaussians of a single width, the optimal accuracy of reconstructing the control
      set is obtained with a FWHM of three pixels. Intended to explore feasibility, the
      BPN presented in the following does not provide reconstruction accuracy adequate
      for immediate application to PET. However, the trained network does reconstruct
      general images independent of the data with which it was trained. Proposed in the
      concluding section are several possible refinements that should permit the
      development of a network capable of fast reconstruction of three-dimensional
      images from the discrete, noisy projection data characteristic of PET.

PMID- 11339748
TI  - Computer-aided bootstrap generation of characteristic curves for radiographic
      imaging systems.
AB  - Determination of the characteristic curve is essential for quantitative
      evaluation of digital as well as screen-film radiographic imaging systems. When
      it is not practical to generate the entire curve through variation of a single
      exposure parameter, bootstrap methods can be used. For the bootstrap method used
      here, curve segments are generated by varying one exposure parameter and multiple
      segments are produced at different exposure levels by varying a second parameter.
      The segments then are joined to form a single composite characteristic curve. If
      the second parameter is one for which the sensitivity of the receptor is not
      constant (such as x-ray tube potential or beam filtration), the shift of each
      segment along the log relative-exposure axis needed to join the overlapping curve
      sections is not known and some form of segment matching must be employed. A
      spline interpolation method and a polynomial fit integral method were developed
      for automatic segment matching and compared. For both methods, the shifts between
      successive segment pairs which result in optimal overlap are determined and the
      cumulative shifts to obtain the complete composite curve are calculated for all
      segments. The two methods are evaluated for several image receptors and with a
      known curve generated from an analytic function. Both methods closely agreed in
      the shifts determined for the image receptors and provided a good visual matching
      of the curve segments. The spline interpolation method more accurately determined
      the appropriate shifts for the mathematically generated curve segments. The
      bootstrap methods can provide complete, accurate characteristic curves, and the
      segment joining program makes the process fast and precise.

PMID- 11339749
TI  - Investigation of human brain hemodynamics by simultaneous near-infrared
      spectroscopy and functional magnetic resonance imaging.
AB  - The aim of this study was to compare functional cerebral hemodynamic signals
      obtained simultaneously by near infrared spectroscopy (NIRS) and by functional
      magnetic resonance imaging (fMRI). The contribution of superficial layers (skin
      and skull) to the NIRS signal was also assessed. Both methods were used to
      generate functional maps of the motor cortex area during a periodic sequence of
      stimulation by finger motion and rest. In all subjects we found a good
      collocation of the brain activity centers revealed by both methods. We also found
      a high temporal correlation between the BOLD signal (fMRI) and the deoxy
      hemoglobin concentration (NIRS) in the subjects who exhibited low fluctuations in
      superficial head tissues.

PMID- 11339750
TI  - A feasible method for clinical delivery verification and dose reconstruction in
      tomotherapy.
AB  - Delivery verification is the process in which the energy fluence delivered during
      a treatment is verified. This verified energy fluence can be used in conjunction
      with an image in the treatment position to reconstruct the full three-dimensional
      dose deposited. A method for delivery verification that utilizes a measured
      database of detector signal is described in this work. This database is a
      function of two parameters, radiological path-length and detector-to-phantom
      distance, both of which are computed from a CT image taken at the time of
      delivery. Such a database was generated and used to perform delivery verification
      and dose reconstruction. Two experiments were conducted: a simulated prostate
      delivery on an inhomogeneous abdominal phantom, and a nasopharyngeal delivery on
      a dog cadaver. For both cases, it was found that the verified fluence and dose
      results using the database approach agreed very well with those using previously
      developed and proven techniques. Delivery verification with a measured database
      and CT image at the time of treatment is an accurate procedure for tomotherapy.
      The database eliminates the need for any patient-specific, pre- or post-treatment
      measurements. Moreover, such an approach creates an opportunity for accurate,
      real-time delivery verification and dose reconstruction given fast image
      reconstruction and dose computation tools.

PMID- 11339751
TI  - Sampling considerations for intensity modulated radiotherapy verification using
      electronic portal imaging.
AB  - A model has been developed to describe the sampling process that occurs when
      intensity modulated radiotherapy treatments (delivered with a multileaf
      collimator) are imaged with an electronic portal imaging device that acquires a
      set of frames with a finite dead-time between them. The effects of the imaging
      duty cycle and frame rate on the accuracy of dosimetric verification have been
      studied. A frame interval of 1 s with 25%, 50% and 75% duty cycle, and a 50% duty
      cycle with frame intervals of 1, 2, 4, 8, and 16 s have been studied for a
      smoothly varying hemispherical intensity profile, and a 50% duty cycle with frame
      intervals of 1, 2, 4, and 8 s for a pixellated distribution. In addition an
      intensity modulated beam for breast radiotherapy has been modeled and imaged for
      0.33 s frame time and 1, 2, and 3 s frame separation. The results show that under
      sparse temporal sampling conditions, errors of the order of 10% may ensue and
      occur with an oscillatory pattern. For the beams studied, imaging with a 1 or 2 s
      frame interval resulted in small errors at the 1%-2% level, for all duty cycles
      shown.

PMID- 11339752
TI  - Analytical scatter kernels for portal imaging at 6 MV.
AB  - X-ray photon scatter kernels for 6 MV electronic portal imaging are investigated
      using an analytical and a semi-analytical model. The models are tested on
      homogeneous phantoms for a range of uniform circular fields and scatterer-to
      detector air gaps relevant for clinical use. It is found that a fully analytical
      model based on an exact treatment of photons undergoing a single Compton scatter
      event and an approximate treatment of second and higher order scatter events,
      assuming a multiple-scatter source at the center of the scatter volume, is
      accurate within 1% (i.e., the residual scatter signal is less than 1% of the
      primary signal) for field sizes up to 100 cm2 and air gaps over 30 cm, but shows
      significant discrepancies for larger field sizes. Monte Carlo results are
      presented showing that the effective multiple-scatter source is located toward
      the exit surface of the scatterer, rather than at its center. A second model is
      therefore investigated where second and higher-order scattering is instead
      modeled by fitting an analytical function describing a nonstationary isotropic
      point-scatter source to Monte Carlo generated data. This second model is shown to
      be accurate to within 1% for air gaps down to 20 cm, for field sizes up to 900
      cm2 and phantom thicknesses up to 50 cm.

PMID- 11339753
TI  - Impact of dose-distribution uncertainties on rectal ntcp modeling. I: Uncertainty
      estimates.
AB  - A trial of nonescalated conformal versus conventional radiotherapy treatment of
      prostate cancer has been carried out at the Royal Marsden NHS Trust (RMH) and
      Institute of Cancer Research (ICR), demonstrating a significant reduction in the
      rate of rectal bleeding reported for patients treated using the conformal
      technique. The relationship between planned rectal dose-distributions and
      incidences of bleeding has been analyzed, showing that the rate of bleeding falls
      significantly as the extent of the rectal wall receiving a planned dose-level of
      more than 57 Gy is reduced. Dose-distributions delivered to the rectal wall over
      the course of radiotherapy treatment inevitably differ from planned
      distributions, due to sources of uncertainty such as patient setup error, rectal
      wall movement and variation in the absolute rectal wall surface area. In this
      paper estimates of the differences between planned and treated rectal dose
      distribution parameters are obtained for the RMH/ICR nonescalated conformal
      technique, working from a distribution of setup errors observed during the
      RMH/ICR trial, movement data supplied by Lebesque and colleagues derived from
      repeat CT scans, and estimates of rectal circumference variations extracted from
      the literature. Setup errors and wall movement are found to cause only limited
      systematic differences between mean treated and planned rectal dose-distribution
      parameter values, but introduce considerable uncertainties into the treated
      values of some dose-distribution parameters: setup errors lead to 22% and 9%
      relative uncertainties in the highly dosed fraction of the rectal wall and the
      wall average dose, respectively, with wall movement leading to 21% and 9%
      relative uncertainties. Estimates obtained from the literature of the uncertainty
      in the absolute surface area of the distensible rectal wall are of the order of
      13%-18%. In a subsequent paper the impact of these uncertainties on analyses of
      the relationship between incidences of bleeding and planned rectal dose
      distributions is explored.

PMID- 11339754
TI  - Impact of dose-distribution uncertainties on rectal ntcp modeling. II:
      Uncertainty implications.
AB  - A trial of nonescalated conformal versus conventional radiotherapy treatment of
      prostate cancer has been carried out at the Royal Marsden NHS Trust (RMH) and
      Institute of Cancer Research (ICR), demonstrating a significant reduction in the
      rate of rectal bleeding reported for patients treated using the conformal
      technique. The rate of bleeding has been shown to fall significantly as the
      extent of rectal wall receiving a planned dose-level in excess of 57 Gy is
      reduced. Dose-distributions delivered to the rectal wall over the course of
      radiotherapy treatment inevitably differ from planned distributions. In a
      previous paper estimates were obtained of the uncertainties in some planned
      rectal dose-distribution parameters generated by patient setup error, rectal wall
      movement and the variable degree of rectal wall distension. Here these
      uncertainties are combined to obtain estimates of the total planning
      uncertainties in rectal dose-distribution parameters thought likely, on the basis
      of mechanistic biological modeling, to correlate strongly with the complication
      rate. Working from these totaled uncertainty values, together with values of
      patient-to-patient and technique-to-technique differences in planned dose
      distribution parameters, it can be inferred that the rectal dose-distribution
      uncertainties: (i) Have only a marginal impact on fits of a normal tissue
      complication probability (ntcp) model to RMH/ICR dose-distribution and grade 1,
      2, 3 bleeding data (slightly flattening observed volume-response curves); (ii)
      only slightly reduce the power of a 2 x 100 patient trial of conformal versus
      conventional prostate radiotherapy to detect a significantly lower rate of grade
      1,2,3 rectal bleeding amongst conformally treated patients; (iii) do not diminish
      the information content of individual planned patient dose-distribution data to
      the point where the fitting of technique-averaged data would provide as sensitive
      a test of the existence of a volume effect as the fitting of individual patient
      data.

PMID- 11339755
TI  - Comparison of the Batho, ETAR and Monte Carlo dose calculation methods in CT
      based patient models.
AB  - This paper shows the contribution that Monte Carlo methods make in regard to dose
      distribution calculations in CT based patient models and the role it plays as a
      gold standard to evaluate other dose calculation algorithms. The EGS4 based BEAM
      code was used to construct a generic 8 MV accelerator to obtain a series of x-ray
      field sources. These were used in the EGS4 based DOSXYZ code to generate beam
      data in a mathematical water phantom to set up a beam model in a commercial
      treatment planning system (TPS), CADPLAN V.2.7.9. Dose distributions were
      calculated with the Batho and ETAR inhomogeneity correction algorithms in
      head/sinus, lung, and prostate patient models for 2 x 2, 5 x 5, and 10 X 10 cm2
      open x-ray beams. Corresponding dose distributions were calculated with DOSXYZ
      that were used as a benchmark. The dose comparisons are expressed in terms of 2D
      isodose distributions, percentage depth dose data, and dose difference volume
      histograms (DDVH's). Results indicated that the Batho and ETAR methods contained
      inaccuracies of 20%-70% in the maxillary sinus region in the head model. Large
      lung inhomogeneities irradiated with small fields gave rise to absorbed dose
      deviations of 10%-20%. It is shown for a 10 x 10 cm2 field that DOSXYZ models
      lateral scatter in lung that is not present in the Batho and ETAR methods. The
      ETAR and Batho methods are accurate within 3% in a prostate model. We showed how
      the performance of these inhomogeneity correction methods can be understood in
      realistic patient models using validated Monte Carlo codes such as BEAM and
      DOSXYZ.

PMID- 11339756
TI  - Technical note: acquisition of CT models for radiotherapy applications with
      reduced tube heating.
AB  - The potential or changing computed tomography (CT) protocols to provide data sets
      that generate high quality digitally reconstructed radiographs (DRRs) from scans
      with very low tube currents is demonstrated. DRRs were generated from CT data
      acquired with slice thickness of 1, 3, and 5 mm, using high current to reduce
      noise in axial images. These DRRs were compared to one generated from a CT scan
      acquired using 1 mm aperture and very low (10 mA) current. The DRR generated via
      this technique is comparable to that generated with high current and 1 mm
      aperture, and higher resolution than from the 3 and 5 mm CT scans.

PMID- 11339757
TI  - Organ/patient geometric variation in external beam radiotherapy and its effects.
AB  - Treatment variation in positioning of the organ/patient with respect to the
      radiation beams causes a temporal dose variation in critical normal tissues
      adjacent to the treatment target. This temporal variation induces uncertainties
      in understanding the normal tissue dose response, thereby limiting reliable
      treatment evaluation and optimization. The aim of this study is to model and
      analyze the temporal variation of organ dose distribution, and its effect on the
      biological effective dose. The study mainly focuses on the temporal dose
      variation caused by intertreatment organ motion/ deformation and daily setup
      error. Sensitivity of the biological effective dose to organ/patient geometric
      variation, dose distribution, and treatment fractionation will be investigated.
      Significant deviation of the biological effective dose could be expected in a
      critical normal structure, even if the cumulative dose deviation in this
      structure is negligible. Patients with similar geometric variation
      characteristics can experience significantly different biological effective dose,
      and the differences are sensitive to the dose distribution and the total number
      of treatment fractions.

PMID- 11339758
TI  - Reducing loss in lateral charged-particle equilibrium due to air cavities present
      in x-ray irradiated media by using longitudinal magnetic fields.
AB  - The underdosing of lesions distal to air cavities, such as those found in upper
      respiratory passages, occurs due to the loss in lateral charged-particle
      equilibrium (CPE). The degree of underdosing worsens for smaller field sizes,
      resulting in more frequent recurrence of the cancer treated. Higher photon
      energies further aggravate the outcome by producing longer second build-up
      regions beyond the cavity. Besides underdosing, the larger lateral spread of
      secondary electron fluence in the air cavity produces diffuse dose distributions
      at the tissue-air interface for shaped or intensity modulated fields. These
      disequilibrium effects create undesirable deviations from the intended treatment.
      The clinical concern is further intensified by the failure of traditional
      treatment planning systems to even account for such defects. In this work, the
      use of longitudinal magnetic fields on the order of 0.5 T is proposed for
      alleviating lateral electronic disequilibrium due to the presence of air cavities
      in the irradiated volume. The magnetic field enforces lateral CPE by restricting
      the lateral range of electrons in the air cavity. The problem is studied in a
      simple water-air-water slab geometry using EGS4 Monte Carlo simulations for 6 MV
      photons. Electronic disequilibrium is evaluated for beams of various sizes,
      shapes and intensity distributions constructed by linear superposition of the
      dose distributions for 0.5 x 0.5 cm2 beamlets. Comparison is also made with 60Co
      irradiation. The results indicate that the lateral confinement of secondary
      electrons in the air cavity by sub-MRI strength longitudinal fields is effective
      in reducing deterioration of dose distributions near tissue-air interfaces. This
      can potentially reduce recurrence rates of cancers such as the larynx carcinoma.

PMID- 11339759
TI  - Dynamic wedge versus physical wedge: a Monte Carlo study.
AB  - The purpose of this study is to analyze the characteristics of dynamic wedges
      (DW) and to compare DW to physical wedges (PW) in terms of their differences in
      affecting beam spectra, energy fluence, angular distribution, contaminated
      electrons, and dose distributions. The EGS4/BEAM Monte Carlo codes were used to
      simulate the exact geometry of a 6 MV beam and to calculate 3-D dose
      distributions in phantom. The DW was simulated in accordance with the segmented
      treatment tables (STT). The percentage depth dose curves and beam profiles for
      PW, DW, and open fields were measured and used to verify the Monte Carlo
      simulations. The Monte Carlo results were found to agree within 2% with the
      measurements performed using film and ionizing chambers in a water phantom. The
      present EGS4 calculation reveals that the effects of a DW on beam spectral and
      angular distributions, as well as electron contamination, are much less
      significant than those for a PW. For the 6 MV photon beam, a 45 degrees PW can
      result in a 30% increase in mean photon energy due to the effect of beam
      hardening. It can also introduce a 5% dose reduction in the build-up region due
      to the reduction of contaminated electrons by the PW. Neither this mean-energy
      increase nor such dose reduction is found for a DW. Compared to a DW, a PW alters
      the photon-beam spectrum significantly. The dosimetric differences between a DW
      and a PW are significant and clearly affect the clinical use of these beams. The
      data presented may be useful for DW commissioning.

PMID- 11339760
TI  - Angular measurement of the cobalt-60 emitted radiation spectrum from a
      radiosurgery irradiator.
AB  - The photon energy spectrum emanating from a Leksell Gamma Knife, Model 23004B,
      was measured between 0.250 and 3.5 MeV with the sources exposed. Measurements
      were made using a 2x2 inch NaI detector enclosed in a lead-shielded apparatus
      having a 1/4 inch diameter measurement aperture, which reduced the amount of
      radiation received by the crystal. All measurements were made one meter above the
      floor within a quadrant toward one side of the Gamma Knife couch. The measured
      spectra displayed the expected 60Co doublet of photon peaks at energies of 1.17
      and 1.33 MeV. These peaks appeared in spectra beginning at approximately 50
      degrees, as one proceeds from a point directly lateral to the source enclosure (0
      degrees) toward the foot of the couch (90 degrees). The average photon energy of
      the spectrum shifts to lower values as the doublet decreases in magnitude with
      increasing angle until almost vanishing at an angle equal to 90 degrees.
      Inserting a 16 cm diameter plastic sphere phantom, provided with the Gamma Knife,
      into the radiation beams increases the low energy photon emissions appearing in
      the spectrum, especially for measurements at the foot of the couch. Implications
      for the design of shielding a treatment room containing the Gamma Knife, Model B,
      and estimation of the radiation exposure to personnel during an emergency
      procedure in the treatment room with the sources exposed are discussed.

PMID- 11339761
TI  - Monte Carlo calculations of AAPM Task Group Report No. 43 dosimetry parameters
      for the MED3631-A/M125I source.
AB  - Brachytherapy dosimetry parameters for MED3631-A/M 125I sources have been
      determined in accordance with the AAPM Task Group No. 43 (TG-43) dosimetry
      protocol. These data were calculated using the *F8 tally from the MCNP4B2 Monte
      Carlo radiation transport code with the DLC-189 cross-section libraries. Due to
      motion of the 125I resin beads and gold-copper markers within the capsule,
      parameters such as the geometry function, radial dose function, dose rate
      constant, and anisotropy function were examined with the beads and markers having
      either "realistic" or "ideal" positions; the realistic position was a weighted
      combination of "vertical" and "diagonal" capsule orientations. The dose rate
      constants for the realistic and ideal geometries, lambda99std(realistic) and
      lambda99std(ideal) were 1.066 and 1.067 cGy h(-1) U(-1), respectively, which were
      within uncertainties of measured values by Wallace and Fan [Med. Phys. 26, 1925
      1931 (1999)] and Li et al. [Med. Phys. 27, 1275-1280 (2000)], 1.06 and 1.067 cGy
      h(-1) U(-1), respectively. The calculated reference dose rate at r0= 1 and
      theta0= 90 degrees for the realistic source geometry was 0.7% less than for the
      ideal source geometry. The anisotropy constants, phian(realistic), for the
      realistic and ideal geometries were 0.948 and 0.965, respectively.
      phian(realistic) matched that (0.941) measured by Wallace and Fan, and
      phian(ideal) was significantly different from that (0.948) calculated by
      Wierzbicki et al. [Med. Phys. 25, 2197-2199 (1998)] for an ideal MED3631-A/S 125I
      source.

PMID- 11339762
TI  - On the applicability of the AAPM TG-60/TG-43 dose calculation formalism to
      intravascular line sources: proposal for an adapted formalism.
AB  - Despite the widely recognized usefulness of the AAPM TG-43 brachytherapy dose
      calculation formalism, a straightforward application of this approach to describe
      the dose distribution about intravascular line sources as proposed by TG-60 may
      be difficult or even impossible, especially when these line sources emit low
      energy photons or beta particles. The causes of these limitations are
      investigated and illustrated by means of some numerical examples. In order to
      solve the observed limitations an adapted formalism is proposed, intended
      specifically for the description of the dose rate distribution about line sources
      but conceptually similar to the TG-43/TG-60 formalism. Several examples are
      presented to illustrate the usefulness of the proposed line source dose
      calculation formalism.

PMID- 11339763
TI  - Fitted dosimetric parameters of high dose-rate 192Ir sources according to the
      AAPM TG43 formalism.
AB  - The purpose of this study is to find fitted functional forms to the anisotropy
      function, F(r, theta), and the radial dose function, g(r), in order to
      characterize dose-rate distributions around all the high-intensity 192Ir sources
      currently in use. Dosimetry data are at present available as tables for: the
      microSelectron HDR ("classic" and "new" design models), the PDR source, and the
      VariSource HDR source, expressed in terms of the AAPM Task Group No. 43
      recommendations. There is only one paper out which introduces a functional form
      to fit the anisotropy function, but only for symmetric sources with respect to
      the transverse axis. However, dosimetric data of the HDR and PDR sources
      mentioned above cannot be reproduced with these functional forms. In our study
      F(r,theta) and g(r) published data are fitted with functional forms in such a way
      that appropriate limits are reached for both functions and the maximum fit error
      approaches the data uncertainty. The average fit error is less than 1% in all
      cases. These functional forms make handling data easier within the treatment
      planning system, avoiding the use of tabulated data.

PMID- 11339764
TI  - Dosimetry of the I-Plant Model 3500 iodine-125 brachytherapy source.
AB  - 125I brachytherapy sources have been widely used for interstitial implants for a
      number of years in several tumor sites, especially the prostate. The design of
      the new I-Plant Model 3500 iodine source is novel, yet its characteristics are
      similar to those of two existing designs, Model 6711 and the Symmetra. Dosimetry
      parameters (including dose rate constant, radial dose function, and anisotropy
      function, as defined by AAPM Task Group 43) were measured with LiF
      thermoluminescent dosimeters in water-equivalent plastic phantoms. The dose rate
      constant was found by direct comparison of calibrated I-Plant Model 3500 and
      Model 6711 seeds in a solid water phantom, to be 1.01 (cGy/h)/U. The radial dose
      function and anisotropy function are similar to those of the Model 6711 and
      Symmetra seeds.

PMID- 11339765
TI  - Comparison of I-125 sources used for permanent interstitial implants.
AB  - The increase in the number of manufacturers of 125I sources used in prostate
      brachytherapy has generated many questions in the radiation oncology community.
      In this investigation, the physical and dosimetric characteristics were evaluated
      for the following sources listed by marketing company and source model: Nycomed
      Amersham 6711 (OncoSeed), Nycomed-Amersham 6702, Mentor IoGold, UroMed Symmetra,
      Imagyn IsoSTAR, UroCor, (PSA, Mallincrkrodt) ProstaSeed, Syncor PharmaSeed,
      SourceTech Medical, (BARD) 125Implant (BrachySource), Med-Tec I-Plant, Best
      Medical Model 2301, DraxImage BrachySeed, and International Brachytherapy, Inc.
      (IBT) InterSource125. The investigation examined the differences in design,
      construction, and the dosimetric characteristics created from each source. The
      dosimetric characteristics of the new sources were compared to that of the
      Amersham 6711 source. Parameter studies have led to the development of a simple
      equation that can be used to clinically convert the standard 6711 source strength
      to an equivalent strength of a new source.

PMID- 11339766
TI  - A theoretical derivation of the nomograms for permanent prostate brachytherapy.
AB  - This study calculates the required minimum radioactivity to deliver a prescribed
      dose of radiation to a target using radioisotopes in permanent prostate
      brachytherapy. Assuming the radioactivity to be in a continuous form, an integral
      equation--Fredholm equation of the first kind, can be formulated with the
      radioactivity density used as the variable. The density distribution to produce a
      uniform volume dose rate is determined using a quadrature method and the radial
      profile behaves smoothly from the zero radius, and peaks sharply approaching the
      volume boundary. The density for Pd-103 is about 1.5 times that of I-125 due to
      its higher spatial attenuation. A nomogram is the relationship between the total
      activity per unit dose (A) and the dimension of the volume (d). Expressing the
      nomogram as A=c X dn U/Gy, then (c,n)= [(0.0098, 2.09) I-125] and [(0.031, 2.25)
      Pd-103]. Compared with the Memorial nomogram, (c,n)=[(0.011,2.2) I-125] and
      [(0.036,2.56) Pd-103], or that quoted by AAPM TG64, (c,n)=[(0.014,2.05) I-125]
      and [(0.056,2.22) Pd-103], our calculation determined an average 33% and 35%
      decrease for I-125, and 89% and 77% decrease for Pd-103, respectively. Two
      reasons for the extra total activity found in the Memorial and AAPM nomograms
      are: (a) An imperfect clinical situation limited by the restraints of implant
      techniques (e.g., use of templates) associated with the presence of adjacent
      normal organs, and (b) source discretization into seeds. When radioactivity is
      clumped as discrete seeds, higher activity is needed because of "wastage" in two
      aspects: (a) Dose cold-spots at intersource spaces, (b) hot-spots around the
      sources. Thus in theory, use of lower activity seeds will require less total
      activity to deliver a prescribed dose. Based on our study, Pd-103 delivers a
      higher therapeutic ratio and a lower integral dose to the patient compared to I
      125.

PMID- 11339767
TI  - Tissue mimicking materials for a multi-imaging modality prostate phantom.
AB  - Materials that simultaneously mimic soft tissue in vivo for magnetic resonance
      imaging (MRI), ultrasound (US), and computed tomography (CT) for use in a
      prostate phantom have been developed. Prostate and muscle mimicking materials
      contain water, agarose, lipid particles, protein, Cu++, EDTA, glass beads, and
      thimerosal (preservative). Fat was mimicked with safflower oil suffusing a random
      mesh (network) of polyurethane. Phantom material properties were measured at 22
      degrees C. (22 degrees C is a typical room temperature at which phantoms are
      used.) The values of material properties should match, as well as possible, the
      values for tissues at body temperature, 37 degrees C. For MRI, the primary
      properties of interest are T1 and T2 relaxations times, for US they are the
      attenuation coefficient, propagation speed, and backscatter, and for CT, the x
      ray attenuation. Considering the large number of parameters to be mimicked,
      rather good agreement was found with actual tissue values obtained from the
      literature. Using published values for prostate parenchyma, T1 and T2 at 37
      degrees C and 40 MHz are estimated to be about 1,100 and 98 ms, respectively. The
      CT number for in vivo prostate is estimated to be 45 HU (Hounsfield units). The
      prostate mimicking material has a T1 of 937 ms and a T2 of 88 ms at 22 degrees C
      and 40 MHz; the propagation speed and attenuation coefficient slope are 1,540 m/s
      and 0.36 dB/cm/MHz, respectively, and the CT number of tissue mimicking prostate
      is 43 HU. Tissue mimicking (TM) muscle differs from TM prostate in the amount of
      dry weight agarose, Cu++, EDTA, and the quality and quantity of glass beads. The
      18 microm glass beads used in TM muscle increase US backscatter and US
      attenuation; the presence of the beads also has some effect on T1 but no effect
      on T2. The composition of tissue-mimicking materials developed is such that
      different versions can be placed in direct contact with one another in a phantom
      with no long term change in US, MRI, or CT properties. Thus, anthropomorphic
      phantoms can be constructed.

PMID- 11339768
TI  - Relation between carbon ion ranges and x-ray CT numbers.
AB  - Measurements of carbon ion ranges in various phantom materials and real bones are
      presented. Together with measured Hounsfield values, an empirical relation
      between ranges and Hounsfield units is derived, which is an important
      prerequisite for treatment planning in carbon ion therapy.

PMID- 11339769
TI  - Comment on "Experimental measurements of dosimetric parameters on the transverse
      axis of a new 125I source".

PMID- 11339770
TI  - Dose-rate constant for Imagyn 125I brachytherapy source.

PMID- 11339771
TI  - Spinal vs general anesthesia: the patient's perspective.

PMID- 11339772
TI  - Fatal and non fatal cardiac arrests related to anesthesia.
AB  - PURPOSE: The aim of this study was to assess the incidence and causes of cardiac
      arrests related to anesthesia. METHODS: All patients undergoing anesthesia over a
      six year period were included in a prospective study. The cardiac arrests
      encountered during anesthesia and the first twelve postoperative hours in the
      PACU or ICU were analysed. For each arrest, partially or totally related to
      anesthesia, the sequence of events leading to the accident was evaluated.
      RESULTS: Eleven cardiac arrests related to anesthesia were identified among the
      101,769 anesthetic procedures (frequency: 1.1/10,000 [0.44-1.72]). Mortality
      related to anesthesia was 0.6/10,000 [0.12-1.06]. Age over 84 yr and an ASA
      physical status > 2 were found to be risk factors of cardiac arrest related to
      anesthesia. The main causes of anesthesia related cardiac arrest were anesthetic
      overdose (four cases), hypovolemia (two cases) and hypoxemia due to difficult
      tracheal intubation (two cases). No cardiac arrests due to alveolar
      hypoventilation were noted during the postoperative periods in either PACU or
      ICU. At least one human error was noted in ten of the eleven cardiac arrests
      cases, due to poor preoperative evaluation in seven. All cardiac arrests totally
      related to anesthesia were classified as avoidable. CONCLUSION: Efforts must be
      directed towards improving preoperative patient evaluation. Anesthetic induction
      doses should be titrated in all ASA 3 and 4 patients. The prediction of difficult
      tracheal intubation, and if required, the use of awake tracheal intubation
      techniques, should remain a priority when performing general anesthesia.

PMID- 11339773
TI  - The attitude of the general public towards preoperative assessment and risks
      associated with general anesthesia.
AB  - PURPOSE: To survey the general public's attitude towards preoperative assessment
      and commonly perceived fears about general anesthesia. METHODS: A province wide
      telephone survey was conducted in Alberta. General and regional anesthesia were
      defined, a scenario involving major knee surgery was described, and participants
      were asked to choose between regional and general anesthesia. Respondents used a
      seven-point scale to rate the importance of seeing an anesthesiologist
      preoperatively and were questioned about the timing of such a visit. Attitudes
      towards commonly perceived fears associated with anesthesia were also assessed.
      RESULTS: A total of 1,216 people were surveyed. Over 30% of respondents felt that
      it was very important to see an anesthesiologist preoperatively, with a total of
      over 60% attributing a high degree of importance to this. Fifty percent felt that
      this assessment should occur on the day prior to surgery. A preference for
      regional or general anesthesia was not expressed in the situation. Approximately
      20% of respondents were very concerned about brain damage, waking up
      intraoperatively and memory loss. Twelve percent were concerned about dying
      intraoperatively. Nine percent expressed concern about postoperative pain, with
      12% reporting being concerned about nausea and vomiting. CONCLUSIONS: The general
      public considers anesthetic assessment on the day prior to surgery an important
      part of preoperative preparation. Fears of brain damage, death and intraoperative
      awareness associated with general anesthesia remain prevalent, suggesting that
      preoperative education of patients should address these concerns. The general
      population was less concerned about realistic fears such as nausea, vomiting and
      postoperative discomfort.

PMID- 11339774
TI  - Endocrine response to surgical stress in three patients over 100 yr.
AB  - PURPOSE: To report the change of plasma epinephrine, norepinephrine, cortisol,
      plasma renin activity, plasma aldosterone and plasma atrial natriuretic peptide
      during general anesthesia in three centenarian patients. CLINICAL FEATURES: Three
      patients aged 101, 101 and 102-yr, underwent a screw fixation of femoral fracture
      under general anesthesia. Plasma concentrations of epinephrine, norepinephrine,
      cortisol, renin activity, aldosterone and atrial natriuretic peptide were
      measured before the induction of anesthesia, 15 min after incision and 60 min
      after the end of surgery. Plasma epinephrine concentrations in the three patients
      increased from 419, 344 and 377 pg x ml(-1) before anesthesia to 688, 534 and 478
      pg x ml(-1) 15 min after skin incision. Plasma norepinephrine concentrations
      increased markedly from 408, 513 and 606 pg x ml(-1) before anesthesia to 2950,
      1864 and 1574 pg x ml(-1) 15 min after skin incision. The cortisol response to
      surgery was similar to that of young adults. Plasma aldosterone and renin
      activity was low throughout anesthesia. Plasma atrial natriuretic peptide
      increased from 353, 367 and 109 pg x ml(-1) before induction to 479, 487 and 168
      pg x ml(-1) 15 min after skin incision. CONCLUSION: Plasma norepinephrine
      concentration in patients over 100 yr increased markedly during anesthesia, while
      plasma renin activity and aldosterone were lower.

PMID- 11339775
TI  - Metabolic, hormonal and gastric fluid and pH changes after different preoperative
      feeding regimens.
AB  - PURPOSE: To evaluate the metabolic, hormonal and gastric fluid and pH changes
      after administration of a small volume of different preoperative feeding
      regimens. METHODS: In a prospective, randomized, double-blind study 375 adult
      patients were allocated to one of five groups. Patients ingested 60 ml honey,
      glucose-fructose-sucrose-maltose mixture (GFSM), apple juice or water two hours
      before surgery or continued their overnight fast (controls). Blood samples were
      obtained from an indwelling venous catheter before the administration of feeding
      regimens and before induction of anesthesia for determination of glucose,
      triglycerides, insulin, epinephrine and norepinephrine concentrations. Before
      anesthesia induction, patients were asked to grade the degree of thirst and
      hunger. After tracheal intubation residual gastric volume (RGV) was suctioned
      through an orogastric tube. RESULTS: Administration of honey, GFSM, apple juice
      or water resulted in increases in RGV without changes in the gastric pH. The
      median RGV values were 15 ml in controls and 20-25 ml in other groups. Thirst was
      noted after administration of fluids containing sugars. Hunger was noted in the
      apple juice group. Plasma concentrations of glucose increased and triglycerides
      decreased after ingestion of fluids containing sugars. Plasma insulin
      concentrations decreased in GFSM and apple juice groups. Norepinephrine
      concentrations increased in the control, apple juice and water groups.
      CONCLUSIONS: Small volumes of fluid increased RGV (P < 0.05). Apple juice
      resulted in increased incidence of thirst and hunger and plasma glucose and
      norepinephrine concentrations. Compared with GFSM or apple juice, honey had a
      gentler effect on plasma glucose and insulin concentrations.

PMID- 11339776
TI  - Neostigmine antagonism of rocuronium block during anesthesia with sevoflurane,
      isoflurane or propofol.
AB  - PURPOSE: To examine the influence of continuing administration of sevoflurane or
      isoflurane during reversal of rocuronium induced neuromuscular block with
      neostigmine. METHODS: One hundred and twenty patients, divided into three equal
      groups, were randomly allocated to maintenance of anesthesia with sevoflurane,
      isoflurane or propofol. Neuromuscular block was induced with rocuronium and
      monitored using train-of-four (TOF) stimulation of the ulnar nerve and recording
      the force of contraction of the adductor pollicis muscle. Neostigmine was
      administered when the first response in TOF had recovered to 25%. At this time
      the volatile agent administration was stopped or propofol dosage reduced in half
      the patients in each group (n = 20 in each group). The times to attain TOF ratio
      of 0.8, and the number of patients attaining this end point within 15 min were
      recorded. RESULTS: The times (mean +/- SD) to recovery of the TOF ratio to 0.8
      were 12.0 +/- 5.5 and 6.8 +/- 2.3 min in the sevoflurane continued and
      sevoflurane stopped groups, 9.0 +/- 8.3 and 5.5 +/- 3.0 min in the isoflurane
      continued and isoflurane stopped groups, and 5.2 +/- 2.8 and 4.7 +/- 1.5 min in
      the propofol continued and propofol stopped groups (P < 0.5-01). Only 9 and 15
      patients in the sevoflurane and isoflurane continued groups respectively had
      attained a TOF ratio of 0.8 within 15 min (P < 0.001 for sevoflurane).
      CONCLUSIONS: The continued administration of sevoflurane, and to a smaller extent
      isoflurane, results in delay in attaining adequate antagonism of rocuronium
      induced neuromuscular block.

PMID- 11339777
TI  - The lumbar paravertebral region provides a novel site to assess neuromuscular
      block at the diaphragm.
AB  - PURPOSE: We evaluated a novel, paravertebral site for assessment of neuromuscular
      block at the diaphragm. The neuromuscular blocking effect of 0.1 mg x kg(-1)
      cisatracurium at the adducting laryngeal muscles, the diaphragm and the adductor
      pollicis (AP) were compared. METHODS: In 24 patients undergoing thyroid surgery,
      evoked responses from the adducting laryngeal muscles and the AP muscle were
      obtained using surface electromyography (EMG). Skin electrodes were placed
      paravertebrally near T12/L1 or L1/L2 (novel position; n = 12) or conventionally
      (n = 12). After stimulation of the recurrent laryngeal, phrenic and ulnar nerves,
      the lag, onset time and maximum effect were measured (0.1 Hz, single twitch) as
      well as the time to reach 25% of T1/T0 (T 25%) using train-of-four stimulation
      every 20 sec. RESULTS: A mean maximum block of more than 94% was reached at all
      sites. Lag, onset time and T 25% at the adducting laryngeal muscles and the
      diaphragm were significantly (P <0.005) shorter than at the AP muscle and did not
      differ significantly between the two diaphragmatic monitoring sites
      (conventional: 64 +/- 21 sec, 166 +/- 41 sec and 20 +/- 3 min vs novel: 60 +/- 16
      sec, 161 +/- 40 sec and 22 +/- 2 min respectively). CONCLUSION: Onset and
      duration of action of 0.1 mg x kg(-1) cisatracurium was shorter at the larynx and
      the diaphragm than at the AP muscle. EMG results obtained from the novel,
      paravertebral site did not differ from the conventional monitoring site at the
      seventh or eighth intercostal space and suggest this alternative site is
      appropriate for monitoring of the diaphragm.

PMID- 11339778
TI  - Desflurane, compared to halothane, augments phenylephrine-induced contraction in
      isolated rat aorta smooth muscle.
AB  - PURPOSE: The mechanism responsible for the mediation of hypertension in response
      to increased desflurane levels is unclear. This study compared the effect of
      desflurane and halothane on phenylephrine (PE)-induced contraction in rat aorta
      ring and the effect of desflurane in the presence and absence of nitric oxide
      (NO) synthase activity. METHODS: Endothelium-free rat aorta rings were exposed
      serially to 10(-7) M, 10(-6) M and 10(-5) M PE alone and subsequently in the
      presence of 2 MAC desflurane and halothane. Secondly, endothelium-free
      preparations were exposed to 10(-6) M PE serially in the presence of 0, 1, 2 and
      3 MAC desflurane and halothane. Thirdly, using an endothelium-intact preparation,
      the effect of desflurane on PE-induced contraction was examined, in the presence
      or absence of NG-nitro-L-arginine (L-NNA), an inhibitor of constitutive and
      inducible NO synthase. RESULTS: Contraction amplitudes secondary to 10(-6) and
      10(-5) M PE in endothelium-free preparations were increased by 74% and 36%
      respectively (P <0.05) in the presence of 2 MAC desflurane compared to controls.
      In endothelium-free preparations, contraction amplitudes secondary to 10(-6) M PE
      were increased in the presence of 1 and 2 MAC desflurane by 32% and 18%
      respectively (P <0.05) and reduced by 16% in the presence of 3 MAC halothane (P
      <0.05). In endothelium-intact preparations an expected absolute increase in
      contraction amplitude occurred in the presence of L-NNA but the desflurane effect
      was detectable both in the presence and absence of L-NNA. CONCLUSION: Our results
      suggest that desflurane may have a local vasoconstrictive effect independent of
      endothelium and NO synthase activity. The mechanism remains to be determined.

PMID- 11339779
TI  - Spinal anesthesia improves the early recovery profile of patients undergoing
      ambulatory knee arthroscopy.
AB  - PURPOSE: We compared the recovery profiles, postoperative complications,
      perioperative OR utilization times, and times to discharge of patients undergoing
      ambulatory knee arthroscopy under spinal anesthesia (SA) or general anesthesia
      (GA). METHODS: In this randomized, prospective study, 84 ASA I-II patients were
      randomized to receive either SA with 50 mg of 1% lidocaine, or a standardized GA.
      Postoperative pain, nausea and vomiting, sedation, OR utilization, postanesthesia
      care unit (PACU), and ambulatory surgical unit (ASU) recovery were compared.
      RESULTS: Patients in the GA group had more pain in the PACU than the SA group
      (61% vs 15%, P <0.01), and a higher incidence of PACU analgesic use (59% vs 7.5%,
      P <0.01). Patients in the SA group were able to drink and eat sooner than the GA
      group (83 +/- 23 vs 95 +/- 22 min, P <0.05 and 88 +/- 27 vs 105 +/- 29 min, P
      <0.01, respectively). The times to sit, walk, and void were similar. The length
      of PACU and ASU stay between the GA and SA groups were similar (67 +/- 17 vs 60
      +/- 19 min, P >0.05 and 122 +/- 27 vs 127.9 +/- 31 min, P >0.05, respectively).
      The incidence of backache was higher in the SA group (35 vs 13.6%, P <0.05) than
      the GA group. However, the incidence of sore throat was higher in the GA compared
      to the SA group (25% vs 2.5%, P <0.01). CONCLUSIONS: SA with 50 mg of 1%
      lidocaine provides an improved recovery profile for ambulatory knee arthroscopy.
      Discharge times were similar, and with the exception of backache and sore throat,
      the incidence of complications was similar.

PMID- 11339780
TI  - Ambulatory surgery for multi-ligament knee reconstruction with continuous dual
      catheter peripheral nerve blockade.
AB  - PURPOSE: Major reconstructive surgery of the knee traditionally requires an
      extended hospital stay for pain management. Continuous peripheral nerve blockade
      is an alternative method of pain control but is seldom used in the ambulatory
      setting. This case illustrates the use of lumbar plexus and sciatic nerve
      peripheral catheters for major knee surgery using intermittent bolus dosing for
      outpatient analgesia. CLINICAL FEATURES: A 20-yr-old male presented for multi
      ligamentous knee reconstruction (posterior collateral ligament and revision
      anterior collateral ligament and lateral collateral ligament). Anesthesia was
      managed with a lumbar plexus and a sciatic nerve peripheral catheter and a light
      general anesthetic. Post-operative analgesia was provided with a 12-hr infusion
      of 0.2% ropivacaine in an over night recovery care centre. Subsequent catheter
      dosing was performed as an outpatient, twice a day using 0.2% ropivacaine, 10 ml
      in each catheter (four injections total). This provided 96 hr of analgesia and
      low supplemental opioid use. CONCLUSION: The use of a lumbar plexus and sciatic
      nerve peripheral catheter offered an alternative to conventional pain control
      that worked well in the ambulatory setting. By providing prolonged unilateral
      lower limb analgesia, extensive knee surgery was performed that would normally
      require a hospital stay for pain control. Using a bolus dosing method the risk of
      local anesthetic complications occurring outside of the hospital with a
      continuous infusion was minimized.

PMID- 11339781
TI  - Sensory blockade of S3 dermatome prevents pain during bladder catheterization.
AB  - PURPOSE: We often encounter patients who do not complain of pain on undergoing
      invasive urogenital or rectal procedures, despite incomplete epidural blockade of
      sacral cutaneous sensation. To clarify whether or not urethral pain is blocked
      faster than sacral cutaneous sensation during lumbar epidural anesthesia, we
      investigated the correlation between occurrence of urethral pain and loss of cold
      sensation in the S1-3 dermatomes. METHODS: In 46 gynecological patients, Group A
      (n=22) received 15 ml of 2% mepivacaine via an epidural catheter inserted
      cephaladly. Group B (n=24) received 5 ml of 2% mepivacaine directly in the
      epidural needle directed caudally and 10 ml of 2% mepivacaine via the epidural
      catheter inserted cephaladly. A Foley catheter was inserted into the urethra 30
      min after the injection. RESULTS: Urethral pain, which was defined as a pained
      facial expression and/or complaint of pain, was observed in seven patients in
      Group A, and none in Group B. The caudad level of epidural blockade was
      significantly lower in patients without urethral pain (S3, median) than with
      urethral pain (L4) (P <0.05). In 39 patients without urethral pain, 19 (49%)
      experienced loss of cold sensation in the S1 dermatome, 27 (69%) in the S2 and 38
      (97%) in the S3 25 min after the injection. CONCLUSION: Blockade of urethral
      visceral pain often occurs before complete sacral somatosensory blockade, and S3
      somatosensory blockade is the important sacral level as an indicator of
      successful urethral sensory blockade.

PMID- 11339782
TI  - Single dose diclofenac suppository reduces post-Cesarean PCEA requirements.
AB  - PURPOSE: To assess the analgesic efficacy of administering, immediately after
      surgery, a single dose of diclofenac (100 mg suppository) to women who had
      undergone lower segment Cesarean section (LSCS) under combined spinal-epidural
      anesthesia, and received post-operative patient-controlled epidural analgesia
      (PCEA) with ropivacaine 0.2% and fentanyl 2 microg x ml(-1). METHODS: Forty-eight
      ASA physical status I or II term parturients scheduled for elective LSCS under
      regional anesthesia were enrolled into this randomised double-blind study. The
      patient-controlled epidural analgesia device was programmed to deliver a bolus of
      4 ml of local anesthetic mixture with a lockout period of ten minutes and an
      hourly limit of 12 ml. There was no baseline infusion. The study commenced upon
      the patient's first demand for analgesia post-operatively and the patients were
      assessed at one, six, 12 and 24 hr post-operatively for pain scores on movement,
      dermatomal level of sensory blockade, degree of motor blockade and volume of
      local anesthetic used. At conclusion of the study, patients' satisfaction scores
      were recorded. RESULTS: The two groups of patients were similar demographically.
      Patients who received a diclofenac suppository used 52.8 +/- 17.8 ml of local
      anesthetic mixture while those who did not, used 74 +/- 25 ml (P <0.005). Pain
      scores and satisfaction scores did not differ significantly between the groups.
      CONCLUSION: A single administration of 100 mg diclofenac suppository is effective
      in reducing post-Cesarean epidural local anesthetic/opioid requirements by 33%
      for the first 24 hr post-operatively.

PMID- 11339783
TI  - Anesthesia for Cesarean section and posterior fossa craniotomy in a patient with
      von Hippel-Lindau disease.
AB  - PURPOSE: To describe the care of a pregnant woman with von Hippel-Lindau disease
      (VHLD) and intracranial mass lesions. CLINICAL FEATURES: A 30-yr-old primigravida
      with VHLD at 35 weeks gestation was seen at the obstetric anesthesia clinic
      because she wished an epidural analgesia during labour. She had a history of
      headaches and dizziness. Further investigations showed an enlarged cerebellar
      hemangioblastoma with significant local mass effects. A combined Cesarean section
      delivery and posterior fossa craniotomy was performed at 37 weeks gestation. A
      general anesthetic with fentanyl, rocuronium, nitrous oxide, oxygen and
      isoflurane was given for Cesarean section delivery. After delivery, isoflurane
      was reduced and propofol infusion at 4-8 mg x kg(-1) x hr(-1) was initiated. The
      patient had an uneventful operative course and recovery. CONCLUSIONS: Patients
      with VHLD may have worsening of preexisting lesions or develop other lesions
      during pregnancy. Some asymptomatic lesions can increase the risk for anesthesia
      complications. These patients need comprehensive assessment before administration
      of anesthesia.

PMID- 11339784
TI  - Anesthesia for cerebral aneurysms: a comparison between interventional
      neuroradiology and surgery.
AB  - PURPOSE: To review the anesthetic management of patients with cerebral aneurysms
      during treatment in the interventional neuroradiology (INR) suite compared with
      in the operating room. METHODS: This was a retrospective chart review of 100
      consecutive patients treated by endovascular coiling compared with 100 patients
      treated by surgical clipping of a cerebral aneurysm. Information compared and
      analyzed included demographics, pre-procedure medical history, neurological
      status including location and size of aneurysm, anesthetic management,
      complications and patient outcome. P < 0.05 was considered significant. RESULTS:
      Patients in the INR group were older (54 +/- 15 vs 49 +/- 12 yr), had a greater
      incidence of pre-procedure cardiorespiratory problems (55 vs 34 patients) and had
      more aneurysms located in the posterior fossa (68 vs 11) (P < 0.05). General
      anesthesia was used in all except seven INR patients who received conscious
      sedation. There were some differences in the anesthetic agents and techniques.
      There was less monitoring of INR patients; temperature (33 vs 99 patients),
      intraarterial catheter (22 vs 100), central venous catheter (4 vs 78), and evoked
      potential monitoring (0 vs 100). There were no differences in the incidence of
      documented complications or in patient outcome. CONCLUSION: There were some
      differences in the anesthetic management of patients undergoing endovascular
      treatment of a cerebral aneurysm compared with treatment in the operating room.
      The patients in the INR suite were sicker and somewhat older and they received
      less invasive monitoring, but the complication rate and outcome did not differ.

PMID- 11339785
TI  - Transesophageal echocardiography diagnosis of tricuspid obstruction by a vena
      cava tumour.
AB  - PURPOSE: To present the anesthetic management for excision of a primary tumour of
      the inferior vena cava. CLINICAL FEATURES: Resection of a primary tumour of the
      inferior vena cava without extension to the right atrium was scheduled without
      extra-corporeal circulation (ECC). The operation consisted of tumour excision
      with transtumoral clamping. During the immediate postoperative period, tricuspid
      obstruction was suspected when a "cannon a wave" was recorded from the right
      atrial pressure curve. Transesophageal echocardiography confirmed the diagnosis
      of tumour obstruction of the tricuspid valve. CONCLUSION: Tricuspid obstruction
      due to postoperative mobilization of a primary tumour of the inferior vena cava
      was diagnosed by transesophageal echocardiography. Perioperative management
      particularities of the primary tumour of the vena cava are discussed.

PMID- 11339786
TI  - Electroconvulsive therapy impairs systolic performance of the left ventricle.
AB  - PURPOSE: In this observational study, we examined left ventricular systolic
      performance during electroconvulsive therapy (ECT), using an echocardiographic
      automated border detection system. METHODS: Nine ASA I or II patients scheduled
      for ECT were studied. Bilateral ECT was performed after the administration of
      propofol 1 mg x kg(-1), succinylcholine 1 mg x kg(-1), and assisted mask
      ventilation with 100% oxygen. Cardiac function was monitored by transthoracic
      echocardiography, prior to anesthesia induction and throughout the ECT procedure
      until ten minutes after the seizure. RESULTS: Increased end-systolic area and
      decreased fractional area change were observed at one minute after the seizure
      compared to the awake condition. No regional wall motion abnormalities were
      observed in all patients both at baseline condition and during the ECT
      CONCLUSION: Systolic performance of the left ventricle estimated by
      echocardiography decreased transiently in the immediate period after the electric
      shock.

PMID- 11339787
TI  - Changes in the intracuff pressure of the laryngeal masks airway caused by
      repeated use.
AB  - PURPOSE: To observe the changes in permeability and elasticity in the cuff of the
      laryngeal mask airway (LMA) caused by repeated use. METHODS: In vitro use was
      simulated on six # 4 LMAs on 140 occasions. Ambient air was insufflated into the
      cuff until a value of 200 mmHg intracuff pressure (ICP) was reached, and this was
      maintained for 50 min. After each simulation, the LMA was sterilized at 121
      degrees C for 20 min. After every 20 simulations insufflation of 40 ml air was
      carried out to determine the maximum value of ICP (initial ICP), and after three
      hours, spontaneous deflation (final ICP) was measured. The values of initial and
      final ICPs throughout the eight tests were attributed to the elastance and the
      permeability of the cuff respectively. At the end of the study the thickness of
      the wall of the cuffs was measured using an optical microscope. RESULTS: The
      initial ICP with the new LMA (first test) was of 191 +/- 4.4 mmHg. This value
      increased from the fifth test onwards until the end of the study. The value of
      the final ICP in the first test was 111 +/- 3 mmHg and decreased with successive
      sterilizations. Between 80 and 100 simulations, initial ICP increased from 186.5
      +/- 2.9 to 191.7 +/- 2.3 (P = 0.006). The thickness of the wall (694 +/- 17
      microns) was inversely related with the elasticity and the permeability of the
      cuff. CONCLUSIONS: The "safe" life-span of the cuff of the LMAs, measured by the
      initial modifications of the physical properties of the silicone during
      simulations, was estimated to be 80-100 uses and was related to the thickness of
      its wall.

PMID- 11339788
TI  - The laryngeal mask airway in infants and children.
AB  - PURPOSE: To compare the effectiveness of various laryngeal mask airway (LMA)
      sizes and their performance during positive pressure ventilation (PPV) in
      paralyzed pediatric patients. METHODS: Pediatric patients (n = 158), < 30 kg, ASA
      1 or 2 were studied. After paralysis, an LMA of the recommended size was inserted
      and connected to a volume ventilator. Fibreoptic bronchoscopy (FOB) was performed
      and graded: 1, larynx only seen; 2, larynx and epiglottis posterior surface seen;
      3, larynx, and epiglottis tip or anterior surface seen--visual obstruction of
      epiglottis to larynx: < 50%; 4, epiglottis down-folded, and its anterior surface
      seen--visual obstruction of epiglottis to larynx: > 50%; 5, epiglottis down
      folded and larynx not seen directly. Inspiratory and expiratory tidal volumes
      (V(T)), and airway pressure were measured by a pneumo-tachometer, and the
      fraction of leakage (F(L)) was calculated. In 79 cases, LMA was used for airway
      maintenance throughout surgery. RESULTS: Successful LMA placement was achieved in
      98% of cases: three failures were due to gastric insufflation. For LMA # 1, 1.5,
      2, and 2.5, FOB grades [median (range)] were 3(1-5), 3(1-5), 1(1-5) and 1(1-3)
      respectively. In smaller LMAs, the cuff more frequently enclosed the epiglottis
      (P < .001). F(L) of LMA # 1 was higher than those of LMA # 1.5 and LMA # 2.5 (P <
      .05), and F(L) of LMA # 2 was higher than that of LMA # 2.5 (P < .05). In the 79
      patients, the number of patients experiencing complications decreased as LMA size
      increased (P < .05). CONCLUSION: Use of the LMA in smaller children results in
      more airway obstruction, higher ventilatory pressures, larger inspiratory leak,
      and more complications than in older children.

PMID- 11339789
TI  - Fatal anaphylactic reaction to oral diclofenac sodium.

PMID- 11339790
TI  - Effects of pirenzepine, omeprazole, lansoprazole, and rabeprazole on human
      neutrophil functions.

PMID- 11339791
TI  - Retropharyngeal neurofibroma presenting with severe kypho-scoliosis: respiratory
      obstruction in postoperative period.

PMID- 11339792
TI  - Is a single vital capacity breath a suitable method for preoxygenation?

PMID- 11339793
TI  - Reconceptualizing personality disorder categories using personality trait
      dimensions: introduction to special section.
AB  - The categorical model of personality disorders has been widely criticized, and
      many argue for it to be reconceptualized or replaced by a dimensional model
      rooted in personality trait research. Such criticisms have forged a much needed
      integration between the previously distinct research areas of normal and abnormal
      personality. The five articles in this special section provide compelling
      evidence for the usefulness of personality traits for describing and explaining
      the complexities of personality disorders among widely varying samples using very
      different assessment strategies.

PMID- 11339794
TI  - Personality profiles and the prediction of categorical personality disorders.
AB  - Personality disorders (PDs) are usually construed as psychiatric categories
      characterized by a unique configuration of traits and behaviors. To generate
      clinical hypotheses from normal personality trait scores, profile agreement
      statistics can be calculated using a prototypical personality profile for each
      PD. Multimethod data from 1,909 psychiatric patients in the People's Republic of
      China were used to examine the accuracy of such hypotheses in the Interpretive
      Report of the Revised NEO Personality Inventory. Profile agreement indices from
      both self-reports and spouse ratings were significantly related to PD symptom
      scores derived from questionnaires and clinical interviews. However, accuracy of
      diagnostic classification was only modest to moderate, probably because PDs are
      not discrete categorical entities. Together with other literature, these data
      suggest that the current categorical system should be replaced by a more
      comprehensive system of personality traits and personality-related problems.

PMID- 11339795
TI  - A structured interview for the assessment of the Five-Factor Model of
      personality: facet-level relations to the axis II personality disorders.
AB  - The Structured Interview for the Five-Factor Model (SIFFM; Trull & Widiger, 1997)
      is an 120-item semistructured interview that assesses both adaptive and
      maladaptive features of the personality traits included in the five-factor model
      of personality, or "Big Five." In this article, we evaluate the ability of SIFFM
      scores to predict personality disorder symptomatology in a sample of 232 adults
      (46 outpatients and 186 nonclinical college students). Personality disorder
      symptoms were assessed using the Personality Diagnostic Questionnaire-Revised
      (PDQ-R; Hyler & Rider, 1987). Results indicated that many of the predicted
      associations between lower-order personality traits and personality disorders
      were supported. Further, many of these associations held even after controlling
      for comorbid personality disorder symptoms. These findings may help inform
      conceptualizations of the personality disorders, as well as etiological theories
      and treatment.

PMID- 11339796
TI  - Predicting dimensions of personality disorder from domains and facets of the Five
      Factor Model.
AB  - We compared the utility of several trait models for describing personality
      disorder in a heterogeneous clinical sample (N = 94). Participants completed the
      Schedule for Nonadaptive and Adaptive Personality (SNAP; Clark, 1993b), a self
      report measure that assesses traits relevant to personality disorder, and two
      measures of the Five-Factor Model: the Revised NEO Personality Inventory (NEO-PI
      R; Costa and McCrae, 1992) and the Big Five Inventory (BFI; John, Donahue, &
      Kentle, 1991). Regression analyses indicated substantial overlap between the SNAP
      scales and the NEO-PI-R facets. In addition, use of the NEO-PI-R facets afforded
      substantial improvement over the Five-Factor Model domains in predicting
      interview-based ratings of DSM-IV personality disorder (American Psychiatric
      Association, 1994), such that the NEO facets and the SNAP scales demonstrated
      roughly equivalent levels of predictive power. Results support assessment of the
      full range of NEO-PI-R facets over the Five-Factor Model domains for both
      research and clinical use.

PMID- 11339797
TI  - Interpersonal variability in dependent personality.
AB  - The interpersonal circumplex (IPC) was recommended as a personality trait
      dimensional model with good potential to identify the phenomenological scope of
      personality disorders whose core dysfunction involves maladaptive expression of
      interpersonal traits. The IPC was then applied to the reconceptualization of
      dependent personality and dependent personality disorder. In Study 1, Pincus and
      Gurtman's (1995) three interpersonal vectors of dependency were validated via
      factor analyses conducted on two large samples (N = 921; N = 472) and a reliable
      self-report measure, the 3 Vector Dependency Inventory (3VDI) was constructed. In
      Study 2, two samples (N = 103; N = 122) of individuals identified as
      predominantly endorsing submissive dependence, exploitable dependence, or love
      dependence, or who were low in aspects of dependency were compared via ANOVA and
      chi-square analyses on parental representations, adult attachment styles,
      loneliness, and pathological attachment. Submissive dependence was associated
      with higher scores on maladaptive constructs (fearful attachment, pathological
      attachment, and loneliness) and was also associated with lower parental
      affiliation and higher maternal control. Love dependence was associated with
      lower scores on maladaptive constructs and higher scores on secure attachment and
      parental affiliation. Variability in dependent phenomenology was related to its
      three component traits. Multiple perspectives on integrating love dependence,
      exploitable dependence, and submissive dependence into a reconceptualization of
      dependent personality disorder were articulated.

PMID- 11339798
TI  - Personality disorders as extreme variants of common personality dimensions: can
      the Five-Factor Model adequately represent psychopathy?
AB  - The present study examined Widiger and Lynam's (1998) hypothesis that psychopathy
      can be represented using the Five-Factor Model (FFM) of personality. Participants
      in the study consisted of 481 21-22-year-old men and women who are part of an
      ongoing longitudinal study. Psychopathy was assessed by the degree of similarity
      between an individual's NEO-PI-R and an expert-generated FFM psychopathy
      prototype. The expert-based prototype supported the account of Widiger and Lynam
      (1998), as did the correlations between the NEO-PI-R Psychopathy Resemblance
      Index (PRI) and the individual personality dimensions. The PRI was also related
      in predicted ways to measures of antisocial behavior, drug use, and
      psychopathology. The results support the contention that psychopathy can be
      understood as an extreme variant of common dimensions of personality, and
      underscore the utility of a dimensional model of personality disorders.

PMID- 11339799
TI  - Commentary on reconceptualizing personality disorder categories using trait
      dimensions.
AB  - The ability of trait models of personality to account for categories of
      personality disorder is examined with particular reference to the five-factor
      approach. Although dimensional models are consistent with the evidence, and trait
      models can accommodate personality disorder categories, it is not clear that such
      models are directly applicable to clinical use. The lower-order or facet
      structure, in particular, needs further development to capture clinical concepts.
      It is also suggested that trait models do not account for all aspects of
      personality disorder-attention also needs to be paid to the organizing and
      integrative functions of personality.

PMID- 11339800
TI  - Further distinctions between coping and defense mechanisms?
AB  - In the current literature there is a great confusion between coping and defense
      mechanisms. As Cramer (1998) points out, a distinction between them is both
      possible and worthwhile in that they possess different cognitive features. Cramer
      proposes two basic criteria: the conscious/unconscious and the
      intentional/unintentional nature of the processes. We focus on a further
      criterion, the manipulation versus revision of one's mental attitudes, which so
      far has been neglected in the relevant literature. We suggest that responses to
      adversity implying manipulation are typical of defense mechanisms, while those
      implying the revision of one's mental attitudes characterize coping strategies.
      Finally, we address emotion-focused coping as the area where coping and defense
      meet, and we suggest that responses displaying defensive features should be
      excluded from the category of coping in accordance with the distinctions
      identified.

PMID- 11339801
TI  - Defense use and defense understanding in children.
AB  - This study investigated the relation between children's use of defense mechanisms
      and their understanding of those defenses. We hypothesized that, once a child
      understands how a particular defense functions, the use of that defense will no
      longer be successful and will be replaced by another defense mechanism that is
      not yet understood. Defense use was assessed from the Thematic Appreception Test
      (TAT) stories told by 122 children; defense understanding was determined from the
      children's understanding of stories portraying defenses. The results indicated
      that younger children (mean age = 7-8) used the defense of denial more than the
      older children (mean age = 9-11). Older children understood the functioning of
      denial and projection better than the younger children. A comparison of children
      who did and did not understand a defense showed that younger children who
      understood the functioning of denial were less likely to themselves use denial.
      Likewise, older children who understood the functioning of projection were less
      likely to use this defense.

PMID- 11339802
TI  - Agreeableness as a moderator of interpersonal conflict.
AB  - This multimethod research linked the Big Five personality dimensions to
      interpersonal conflicts. Agreeableness was the focus because this dimension is
      associated with motives to maintain positive interpersonal relations. Converging
      responses to both hypothetical conflicts and to diary records of actual daily
      interpersonal conflicts across a two-week period were assessed. Agreeableness was
      expected to moderate affective responses and tactical choices during conflicts.
      Patterns of daily conflict were related to self-reported reactions to
      hypothetical conflicts and to teacher-rated adjustment in adolescents. As
      predicted, Agreeableness was related to responsiveness to conflict. Agreeableness
      differences and use of destructive tactics in conflict were significantly related
      to evaluations of the individual's adjustment by knowledgeable raters. Among the
      Big Five dimensions, Agreeableness was most closely associated with processes and
      outcomes during interpersonal conflict.

PMID- 11339803
TI  - Carbohydrate composition of Carcinus aestuarii hemocyanin.
AB  - The hemocyanin of the crab Carcinus aestuarii contains a carbohydrate moiety that
      represents 1.6% of protein mass. This carbohydrate content is higher than that
      exhibited by other arthropod hemocyanins so far investigated. By combination of
      FPLC ion exchange chromatography and reverse-phase HPLC, the native oligomeric
      protein can be resolved into three major and one minor electrophoretically pure
      fractions that are found to be homogeneous by N-terminal sequencing and
      correspond to the subunit polypeptide chains. Sugar analysis on the different
      subunits reveals that the subunit referred to as Ca2 is glycosylated, with a
      carbohydrate content of 6.3%. By Ca2 trypsin digestion, separation of
      glycopeptides, and amino acid sequencing, three consensus sequences for O
      glycosylation and one for N-glycosylation were found. MALDI-MS was applied for
      the determination of the molecular masses of the various glycopeptides and
      peptides after removal of carbohydrates by neuraminidase and alpha-N
      acetylgalactosaminidase.

PMID- 11339804
TI  - Truncated forms of the recombinant Escherichia coli ADP-glucose
      pyrophosphorylase: the importance of the N-terminal region for allosteric
      activation and inhibition.
AB  - Truncated forms of Escherichia coli ADPglucose pyrophosphorylase were constructed
      using recombinant DNA techniques. A truncated form of the enzyme having the first
      11 amino acid residues from the N-terminus and 2 amino acid residues from the C
      terminus deleted was found to be highly active in absence of activator. A 1.6
      fold activation by 1.5 mM fructose 1,6 bis-phosphate was observed for the
      truncated enzyme as compared to the 30-fold activation seen for the intact
      enzyme. Inhibition of the truncated enzyme by AMP was less than that seen with
      the intact enzyme. Similar properties were displayed by an enzyme truncated only
      at the N-terminal. Conversely, the C-terminal truncated enzyme shortened by 2
      amino acid residues at the C-terminus is as sensitive as the intact enzyme to
      activation and inhibition. These results suggest that the N-terminal region is
      required for allosteric regulation of the enzyme.

PMID- 11339805
TI  - Hyperglycemia and the O-GlcNAc transferase in rat aortic smooth muscle cells:
      elevated expression and altered patterns of O-GlcNAcylation.
AB  - Hyperglycemia leads to vascular disease specific to diabetes mellitus. This
      pathology, which results from abnormal proliferation of smooth muscle cells in
      arterial walls, may lead to cataract, renal failure, and atherosclerosis. The
      hexosamine biosynthetic pathway is exquisitely responsive to glucose
      concentration and plays an important role in glucose-induced insulin resistance.
      UDP-GlcNAc: polypeptide O-N-acetylglucosaminyltransferase (O-GlcNAc transferase;
      OGTase) catalyzes the O-linked attachment of single GlcNAc moieties to serine and
      threonine residues on many cytosolic or nuclear proteins. Polyclonal antibody
      against OGTase was used to examine the expression of OGTase in rat aorta and
      aortic smooth muscle (RASM) cells. OGTase enzymatic activity and expression at
      the mRNA and protein levels were determined in RASM cells cultured at normal (5
      mM) and at high (20 mM) glucose concentrations. OGTase mRNA and protein are
      expressed in both endothelial cells and smooth muscle cells in the aorta of
      normal rats. In both cell types, the nucleus is intensely stained, while the
      cytoplasm stains diffusely. Immunoelectron microscopy shows that OGTase is
      localized to euchromatin and around the myofilaments of smooth muscle cells. In
      RASM cells grown in 5 mM glucose, OGTase is also located mainly in the nucleus.
      Hyperglycemic RASM cells also display a relative increase in OGTase's p78 subunit
      and an overall increase protein and activity for OGTase. Biochemical analyses
      show that hyperglycemia qualitatively and quantitatively alters the glycosylation
      or expression of many O-GlcNAc-modified proteins in the nucleus. These results
      suggest that the abnormal O-GlcNAc modification of intracellular proteins may be
      involved in glucose toxicity to vascular tissues.

PMID- 11339806
TI  - Glucuronidation of linoleic acid diols by human microsomal and recombinant UDP
      glucuronosyltransferases: identification of UGT2B7 as the major isoform involved.
AB  - Recent reports suggest that linoleic acid (LA) epoxides and diols are associated
      with important physiological, pharmacological, and pathological events in vivo.
      We have shown recently that LA-diols are excellent substrates for human liver
      microsomal UDP-glucuronosyltransferases (UGTs); however, it is not known if other
      human tissues glucuronidate LA-diols or which UGT isozyme(s) is involved. The
      present studies with human intestinal microsomes indicate that glucuronidation of
      LA-diols occurs throughout the gastrointestinal tract, with the highest activity
      in the small intestine. LA-diols yielded exclusively hydroxyl-linked
      glucuronides, whereas LA yielded the carboxyl-linked glucuronide. Studies with
      human recombinant UGTs demonstrated that only UGT2B7 glucuronidated LA and LA
      diols. Kinetic analysis with UGT2B7 yielded apparent K(m) values in the range of
      40-70 microM and V(max) values from 4.5 to 5.4 nmol/mg x min. These studies
      indicate that LA and LA-diols are excellent substrates for intestinal UGTs and
      provide the first evidence for UGT2B7 being the major isoform involved.

PMID- 11339807
TI  - Isogloboside biosynthesis in metastatic R3230AC cells results from a decreased
      GM3 synthase activity.
AB  - We have determined that the production of a metastasis-associated neutral
      glycosphingolipid, isogloboside (iGb(4)Cer, GalNAcbeta1-3Galalpha1-3Galbeta1
      4Glcbeta1-O-ceramide) is associated with the loss of G(M3) synthase activity.
      Assays for neutral glycosphingolipid-forming glycosyltransferases in cells
      producing various levels of iGb(4)Cer revealed no consistent differences that
      could account for the difference in iGb(4)Cer biosynthesis. However, comparison
      of the activity of G(M3) synthase in homogenates of these two cell types revealed
      that cells that did not synthesize iGb(4)Cer had activity significantly greater
      than that of cells possessing this antigen. Furthermore, somatic cell hybrids
      generated using clones of the iGb(4)Cer -producing and nonproducing cell lines
      lacked iGb(4)Cer while possessing high levels of G(M3) synthase activity. When
      iGb(4)Cer-producing cells were transfected with a G(M3) synthase expression
      vector, all of the resultant clones were negative for iGb(4)Cer production. The
      results of these studies clearly show that the presence of G(M3) synthase
      prevents the formation of iGb(4)Cer in these cells.

PMID- 11339808
TI  - Mechanisms of action of malondialdehyde and 4-hydroxynonenal on xanthine
      oxidoreductase.
AB  - Studies have been made on the possible involvement of malondialdehyde (MDA) and
      (E)-4-hydroxynon-2-enal (HNE), two terminal compounds of lipid peroxidation, in
      modifying xanthine oxidoreductase activity through interaction with the oxidase
      (XO) and/or dehydrogenase (XDH) forms. The effect of the two aldehydes on XO
      (reversible, XO(rev), and irreversible, XO(irr)) and XDH was studied using
      xanthine oxidase from milk and xanthine oxidoreductase partially purified from
      rat liver. The incubation of milk xanthine oxidase with these aldehydes resulted
      in the inactivation of the enzyme following pseudo-first-order kinetics: enzyme
      activity was completely abolished by MDA (0.5-4 mM), while residual activity (5%
      of the starting value) associated with an XO(irr) form was always observed when
      the enzyme was incubated in the presence of HNE (0.5-4 mM). The addition of
      glutathione to the incubation mixtures prevented enzyme inactivation by HNE. The
      study on the xanthine oxidoreductase partially purified from rat liver showed
      that MDA decreases the total enzyme activity, acting only with the XO forms. On
      the contrary HNE leaves the same level of total activity but causes the
      conversion of XDH into an XO(irr) form.

PMID- 11339809
TI  - Effect of cardiolipin on proton permeability of phospholipid liposomes: the role
      of hydration at the lipid-water interface.
AB  - The effect of cardiolipin on the proton permeability of dipalmitoyl
      phosphatidylcholine small unilamellar vesicles was examined by utilizing the pH
      dependent fluorescence emission of 5- (and 6-) carboxyfluorescein. It has been
      found that the proton permeability of the phospholipid bilayer was greatly
      enhanced in the presence of cardiolipin, an acidic phospholipid mainly found in
      the inner mitochondrial membranes. In the presence of bovine heart cardiolipin,
      the bilayer surface hydration, as assessed with the fluorescence lifetime of 1
      anilinonaphthalene-8-sulfonic acid, was increased, while hydration in the acyl
      chain region was not altered. In addition, the bilayer fluidity was also not
      affected. Taken together, these results suggest that the lipid-water interface is
      the major energy barrier for proton permeation of the bilayer vesicles, and
      alteration to properties of this interface by cardiolipin headgroup appears to be
      responsible for the enhanced proton permeability.

PMID- 11339810
TI  - Regulation of subcellular localization of the aryl hydrocarbon receptor (AhR).
AB  - The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor
      that mediates the toxicity of dioxin and other xenobiotics. In the absence of
      exogenous ligand, AhR is cytosolic. We investigated how AhR is retained in the
      cytosol and how dioxin induces AhR to move to the nucleus. Disruption of nuclear
      export of AhR by the nuclear export inhibitor leptomycin B (LMB) or by mutation
      of the AhR nuclear export signal resulted in nuclear accumulation of AhR in the
      absence of exogenous ligand. Mutation of the AhR nuclear localization signal
      resulted in defects in nuclear import of AhR in both the presence and the absence
      of exogenous ligand. Dioxin treatment caused a more rapid accumulation of AhR in
      the nucleus than LMB treatment. In the presence of both dioxin and LMB, nuclear
      accumulation of AhR was more rapid than in the presence of dioxin alone. Our
      results show that AhR shuttles between the nucleus and the cytosol in the absence
      of exogenous ligand. Binding of ligand induces an increase in the rate of nuclear
      import of AhR but does not eliminate nuclear export of AhR.

PMID- 11339811
TI  - Pregnancy zone protein-tissue-type plasminogen activator complexes bind to low
      density lipoprotein receptor-related protein (LRP).
AB  - Tissue-type plasminogen activator (t-PA), is a serine proteinase that catalyzes
      the initial and rate-limiting step in the fibrinolytic cascade. Its plasma
      activity is determined by the rate of release into the bloodstream, the rate of
      inhibition by plasminogen-activator inhibitor type 1 (PAI-1) and the rate of
      hepatic clearance. Two receptor systems contribute to the clearance of t-PA: the
      mannose receptor and the low-density lipoprotein receptor-related protein (LRP)
      that removes free t-PA as well as t-PA-PAI-1 complexes from the blood. During
      pregnancy a significant rise in the plasma levels of pregnancy zone protein (PZP)
      is observed, while alpha(2)-macroglobulin (alpha(2)-M) remains constant.
      Interestingly, the fibrinolytic activity is decreased during this period. In this
      context, we have recently demonstrated the in vitro formation of PZP-t-PA
      complexes. Here, we purified LRP from human placenta by affinity chromatography
      and then analyzed the binding specificity and affinity of PZP-proteinase
      complexes to the receptor by enzyme immunoassay (EIA). Our results clearly
      established that the binding of PZP-t-PA complexes to LRP was specific,
      saturable, and with K(d) = 337 +/- 31 nM. Moreover, by using the same EIA, we
      further observed that this binding was inhibited by receptor-associated protein.
      These data suggest that PZP, by binding to t-PA and promoting its clearance via
      LRP, might contribute in vivo to the downregulation of the fibrinolytic activity
      during pregnancy.

PMID- 11339812
TI  - Arginine 91 is not essential for flavin incorporation in hepatic cytochrome b(5)
      reductase.
AB  - Cytochrome b(5) reductase (cb5r) catalyzes the transfer of reducing equivalents
      from NADH to cytochrome b(5). Utilizing an efficient heterologous expression
      system that produces a histidine-tagged form of the hydrophilic, diaphorase
      domain of the enzyme, site-directed mutagenesis has been used to generate cb5r
      mutants with substitutions at position 91 in the primary sequence. Arginine 91 is
      an important residue in binding the FAD prosthetic group and part of a conserved
      "RxY(T)(S)xx(S)(N)" sequence motif that is omnipresent in the "ferredoxin:NADP(+)
      reductase" family of flavoproteins. Arginine 91 was replaced with K, L, A, P, D,
      Q, and H residues, respectively, and all the mutant proteins purified to
      homogeneity. Individual mutants were expressed with variable efficiency and all
      exhibited molecular masses of approximately 32 kDa. With the exception of R91H,
      all the mutants retained visible absorption spectra typical of a flavoprotein,
      the former being produced as an apoprotein. Visible absorption spectra of R91A,
      L, and P were red shifted with maxima at 458 nm, while CD spectra indicated an
      altered FAD environment for all the mutants except R91K. Fluorescence spectra
      showed a reduced degree of intrinsic flavin fluorescence quenching for the R91K,
      A, and P, mutants, while thermal stability studies suggested all the mutants,
      except R91K, were somewhat less stable than the wild-type domain. Initial-rate
      kinetic measurements demonstrated that the mutants exhibited decreased
      NADH:ferricyanide reductase activity with the R91P mutant retaining the lowest
      activity, corresponding to a k(cat) of 283 s(-1) and a K(NADH)(m) of 105 microM,
      when compared to the wild-type domain (k(cat) = 800 s(-1) K(NADH)(m) = 6 microM).
      These results demonstrate that R91 is not essential for FAD binding in cb5r;
      however, mutation of R91 perturbs the flavin environment and alters both
      diaphorase substrate recognition and utilization.

PMID- 11339813
TI  - Characterization of Rhodobacter sphaeroides cytochrome c(2) proteins with altered
      heme attachment sites.
AB  - In c-type cytochromes, heme is attached to the polypeptide via thioether linkages
      between vinyl groups on the tetrapyrrole ring and cysteine thiols in a CX(2)CH
      motif. To study the role of the heme-binding site in c-type cytochrome assembly
      and function, we generated amino acid changes in this region of Rhodobacter
      sphaeroides cytochrome c(2) ((15)Cys-Gln-Thr-Cys-His(19)). Amino acid
      substitutions at Cys(15), Cys(18), or His(19) produced mutant proteins that did
      not support growth via photosynthesis where this electron carrier is required.
      Many of these changes appeared to slow signal peptide removal, suggesting that
      heme attachment is coupled to processing of the c-type cytochrome precursor
      protein. Inserting an alanine between the cysteine ligands (CycA-Ins17A) did not
      significantly alter the behavior of this protein in vivo and in vitro, suggesting
      that the existence of 2 residues between cysteine thiols is not essential for
      heme attachment to a Class I c-type cytochrome like cytochrome c(2).

PMID- 11339814
TI  - Purification, molecular cloning, and functional expression of dog liver
      microsomal acyl-CoA hydrolase: a member of the carboxylesterase multigene family.
AB  - To clarify the reason for the high acyl-CoA hydrolase (ACH) activity found in dog
      liver microsomes, the ACH was purified to homogeneity using column
      chromatography. The purified enzyme, named ACH D1, exhibited a subunit molecular
      weight of 60 KDa. The amino terminal amino acid sequence showed a striking
      homology with rat liver carboxylesterase (CES) isozymes. ACH D1 possessed
      hydrolytic activities toward esters containing xenobiotics in addition to acyl
      CoA thioesters, and these activities were inhibited by a specific inhibitor of
      CES or by CES RH1 antibodies. These findings suggest that this protein is a
      member of the CES multigene family. Since ACH D1 appears to be a protein
      belonging to the CES family, we cloned the cDNA from a dog liver lambdagt10
      library with a CES-specific probe. The clone obtained, designated CES D1,
      possessed several motifs characterizing CES isozymes, and the deduced amino acid
      sequences were 100% identical with those of ACH D1 in the first 18 amino acid
      residues. When it was expressed in V79 cells, it showed high catalytic activities
      toward acyl-CoA thioesters. In addition, the characteristics of the expressed
      protein were identical with those of ACH D1 in many cases, suggesting that CES D1
      encodes liver microsomal ACH D1.

PMID- 11339815
TI  - Glutathiolation of the proteasome is enhanced by proteolytic inhibitors.
AB  - The proteasome inhibitors lactacystin, clastro lactacystin beta-lactone, or tri
      leucine vinyl sulfone (NLVS), in the presence of [(35)S]cysteine/methionine,
      caused increased incorporation of (35)S into cellular proteins, even when protein
      synthesis was inhibited by cycloheximide. This effect was blocked by incubation
      with the glutathione synthesis inhibitor buthionine sulfoximine. Proteasome
      inhibitors also enhanced total glutathione levels, increased reduced/oxidized
      glutathione ratio (GSH/GSSG) and upregulated gamma-glutamylcysteine synthetase
      (rate-limiting in glutathione synthesis). Micromolar concentrations of GSH, GSSG,
      or cysteine stimulated the chymotrypsin-like activity of purified 20S proteasome,
      but millimolar GSH or GSSG was inhibitory. Interestingly, GSH did not affect 20S
      proteasome's trypsin-like activity. Enhanced proteasome glutathiolation was
      verified when purified preparations of the 20S core enzyme complex were incubated
      with [(35)S]GSH after pre-incubation with any of the inhibitors. NLVS,
      lactacystin or clastro lactacystin beta-lactone may promote structural
      modification of the 20S core proteasome, with increased exposure of cysteine
      residues, which are prone to S-thiolation. Three main conclusions can be drawn
      from the present work. First, proteasome inhibitors alter cellular glutathione
      metabolism. Second, proteasome glutathiolation is enhanced by inhibitors but
      still occurs in their absence, at physiological GSH and GSSG levels. Third,
      proteasome glutathiolation seems to be a previously unknown mechanism of
      proteasome regulation in vivo.

PMID- 11339816
TI  - Importance of amino acid residue 474 for substrate specificity of canine and
      human cytochrome p450 3A enzymes.
AB  - Canine cytochromes P450 3A12 and 3A26 are identical in sequence at 481 of 503
      amino-acid positions but exhibit different substrate specificities. A recent
      study utilizing chimeric enzymes and site-directed mutagenesis identified three
      residues (187, 368, and 369) that contribute to differences in steroid
      hydroxylation and also indicated the presence of additional determinants of
      specificity among the 44 carboxyl terminal residues. Therefore, three 3A26
      multiple mutants (I187T-S368P-V369I-S467P, I187T-S368P-V369I-S474P, and I187T
      S368P-V369I-R476K-I477L-T479A-R480Q) were constructed. Insertion of 3A12 residue
      Pro-474 into 3A26 I187T-S368P-V369I resulted in metabolite profiles with
      testosterone, androstenedione, and progesterone very similar to 3A12.
      Substitution of Pro-474 with Ser in P450 3A12 or human 3A4 significantly
      increased 2beta-hydroxylase activity with all three steroids. Residue 474 was
      also found to be an important contributor to diazepam metabolism by the canine
      and human enzymes. The results provide further evidence for the role of steric
      constraints exerted by the enzyme in P450 3A-mediated oxidations.

PMID- 11339817
TI  - A Rep recognition sequence is necessary but not sufficient for nicking of DNA by
      adeno-associated virus type-2 Rep proteins.
AB  - The strand-specific, site-specific endonuclease (nicking) activity of the Rep68
      and Rep78 (Rep68/78) proteins of adeno-associated virus type 2 (AAV) is involved
      in AAV replication, and appears to be involved in AAV site-specific integration.
      Rep68/78 cuts within the inverted terminal repeats (ITRs) of the AAV genome and
      in the AAV preferred integration locus on human chromosome 19 (AAVS1). The known
      endonuclease cut sites are 11-16 bases away from the primary binding sites, known
      as Rep recognition sequences (RRSs). A linear, double-stranded segment of DNA,
      containing an RRS and a cut site, has previously been shown to function as a
      substrate for the Rep68/78 endonuclease activity. We show here that mutation of
      the Rep recognition sequence, within such a DNA segment derived from the AAV
      ITRs, eliminates the ability of this substrate to be cleaved detectably by Rep78.
      Rep78 nicks the RRS-containing site from AAVS1 about half as well as the linear
      ITR sequence. Eighteen other RRS-containing sequences found in the human genome,
      but outside AAVS1, are not cleaved by Rep78. These results may help to explain
      the specificity of AAV integration.

PMID- 11339818
TI  - Metabolism of DHEA by cytochromes P450 in rat and human liver microsomal
      fractions.
AB  - Administration of dehydroepiandrosterone (DHEA) to rodents produces many unique
      biological responses, some of which may be due to metabolism of DHEA to more
      biologically active products. In the current study, DHEA metabolism was studied
      using human and rat liver microsomal fractions. In both species, DHEA was
      extensively metabolized to multiple products; formation of these products was
      potently inhibited in both species by miconazole, demonstrating a principal role
      for cytochrome P450. In the rat, use of P450 form-selective inhibitors suggested
      the participation of P4501A and 3A forms in DHEA metabolism. Human liver samples
      displayed interindividual differences in that one of five subjects metabolized
      DHEA to a much greater extent than the others. This difference correlated with
      the level of P4503A activity present in the human liver samples. For one subject,
      troleandomycin inhibited hepatic microsomal metabolism of DHEA by 78%, compared
      to 81% inhibition by miconazole, suggesting the importance of P4503A in these
      reactions. Form-selective inhibitors of P4502D6 and P4502E1 had a modest
      inhibitory effect, suggesting that these forms may also contribute to metabolism
      of DHEA in humans. Metabolites identified by LC-MS in both species included
      16alpha-hydroxy-DHEA, 7alpha-hydroxy-DHEA, and 7-oxo-DHEA. While 16alpha-hydroxy
      DHEA appeared to be the major metabolite produced in rat, the major metabolite
      produced in humans was a mono-hydroxylated DHEA species, whose position of
      hydroxylation is unknown.

PMID- 11339819
TI  - Laminin-10 mediates basal and EGF-stimulated motility of human colon carcinoma
      cells via alpha(3)beta(1) and alpha(6)beta(4) integrins.
AB  - Signals from the epidermal growth factor (EGF) receptor and integrin-dependent
      adhesion to laminin contribute to the progression and metastasis of colonic
      tumors. However, little is know about the mechanisms by which these signals
      cooperate. Recently, we have reported that the colon cancer cell line LIM1215
      secretes and adhere to autocrine laminin-10 via multiple integrin receptors and
      that EGF stimulates spreading of these cells on the same substrate. In this
      report, we investigate the effect of EGF and laminin-10 on colon cancer cell
      migration in vitro. EGF stimulates migration of LIM1215 cells in a wound healing
      assay. The response to EGF is inhibited by anti-EGF receptor antibody 528, the
      EGF receptor kinase inhibitor AG-1478, or the MAP kinase kinase inhibitor PD98059
      but not the PI3-K inhibitor wortmannin. Using Transwell migration chambers, we
      demonstrate that laminin-10 but not collagen-I, collagen-IV, or a commercial
      preparation of human placental laminin is a potent motility factor for LIM1215
      cells. The migration response to laminin-10 is increased upon stimulation of the
      cells with EGF and correlates with the up-regulation of alpha(6)beta(4) integrin
      expression as measured by analysis of Triton X-100-soluble cellular extracts. The
      results from integrin inhibition experiments indicate that basal migration on
      laminin-10 is mediated by alpha(3)beta(1) but not alpha(2)beta(1) nor
      alpha(6)beta(4) integrins. Alpha(3) blocking antibodies also inhibited EGF
      stimulated chemokinetic migration of LIM1215 cells on laminin-10. However, in
      contrast to unstimulated cells, alpha(6) or beta(4) integrin-blocking antibodies
      inhibited the migration of EGF-stimulated cells by up to 50%. Taken together,
      these results support the cooperative role of EGF receptor and laminin-10 on
      colon cancer cell motility and suggest a critical role for both the
      alpha(3)beta(1) and the alpha(6)beta(4) integrins in this process.

PMID- 11339820
TI  - Bacterial heat shock protein-60 increases epithelial cell proliferation through
      the ERK1/2 MAP kinases.
AB  - Heat shock proteins (hsp) have important roles in the regulation and protection
      of both prokaryotic and eukaryotic cells, especially during environmental stress.
      Hsps are also important bacterial virulence factors. We investigated whether
      bacterial hsp60 can alter epithelial cell mitogen-activated protein kinase (MAPK)
      signaling and cell proliferation. Human skin keratinocytes (HaCaT cell line) were
      cultured in the presence of hsp60 purified from Actinobacillus
      actinomycetemcomitans, an important oral pathogen. Protein kinases in the ERK1/2
      and p38 MAPK signaling pathways were probed with kinase-specific and
      phosphorylation-site-specific antibodies on Western blots. In quiescent cultures,
      hsp60 increased ERK1/2 phosphorylation in a sustained manner and p38
      phosphorylation transiently. Hsp60 also increased epithelial cell proliferation
      by about 30%. Inhibition of the ERK1/2 pathway by PD 98059 (a MEK1 inhibitor)
      reversed partially ERK1/2 phosphorylation and totally cell proliferation
      indicating that the ERK1/2 MAPK pathway is involved in the hsp60-induced cell
      growth. This was supported by findings that hsp60 stimulated phosphorylation of
      RSK1/2 and cyclic AMP response element-binding protein and increased expression
      of transcription factors c-Jun and c-Fos. Recombinant human hsp60 did not alter
      ERK1/2 or p38 phosphorylation and had no effect on epithelial cell proliferation.
      Inhibition of p38 MAPK pathway by SB 203580 increased both ERK1/2 phosphorylation
      and cell proliferation demonstrating that the inhibitor can either directly or
      indirectly activate the ERK1/2 MAPK pathway. The results show that exogenous
      bacterial hsp60 is able to activate ERK1/2 phosphorylation and thereby cause
      increased epithelial proliferation. In case of mucosal infection this effect may
      either lead to increased wound repair or participate in the pathological
      mechanism of some bacterial diseases that involve increased epithelial
      proliferation.

PMID- 11339821
TI  - EGR-1, a UV-inducible gene in p53(-/-) mouse cells.
AB  - Changes in gene expression were examined in p53(-/-) and p53(+/+) mouse cells
      after ultraviolet (UV) irradiation. Differential display was used to identify
      differentially expressed gene(s) in UV-treated p53(-/-) and p53(+/+) cells. One
      of the differentially expressed genes was EGR-1 (early growth response gene-1),
      which was shown to be induced only in p53(-/-) cells. The induction of this gene
      by UV was detected as early as 0.5 h, peaked at 2 h, and returned to normal
      levels by 4 h. De novo protein synthesis was not required for UV-induced EGR-1
      expression in p53(-/-) cells. Pretreatment of p53(-/-) cells with suramin, an
      inhibitor of growth factor receptors, completely suppressed UV-induced EGR-1
      expression, suggesting that the induction may be mediated via the growth factor
      receptors. The presence of wild-type p53 suppressed the induction of EGR-1 after
      UV treatment. Overexpression of EGR-1 promoted the UV-induced transformation in
      p53(+/+) cells, but not in p53(-/-) cells. These data suggested that EGR-1 may be
      an important player in the UV responses of mammalian cells and may influence UV
      induced transformation.

PMID- 11339822
TI  - Colocalization prostacyclin (PGI2) synthase--caveolin-1 in endothelial cells and
      new roles for PGI2 in angiogenesis.
AB  - In vascular cells, prostacyclin (PGI2) synthase (PGI2s) has been localized in the
      endoplasmic reticulum of endothelial cells and in the nuclear and plasma membrane
      of smooth muscle cells. In human umbilical vein endothelial (HUVE) cells, we
      detected the enzyme in abundant cytoplasmic vesicles apparently originating from
      the plasma membrane and similar to those stained by gold-albumin, which interacts
      with a caveolar receptor. This prompted us to try a direct confocal microscopy
      approach aimed at colocalizing gold-albumin, caveolin-1, and PGI2 synthase.
      Moreover, the staining of HUVE cells with an anti-BiP7Grp78 antibody (a marker of
      endoplasmic reticulum) shows a perinuclear localization, sharply separated from
      PGI2 synthase localization. The results indicate that more than 80% of the enzyme
      resides in cellular sites costaining with caveolin-1 antibody and gold-albumin.
      This evidence was confirmed by the demonstration that PGI2 synthase and caveolin
      1 coimmunoprecipitate in HUVE cell lysates and that they are associated to
      detergent-insoluble membrane domains in the same low-density fractions of a
      sucrose gradient. In addition, depletion of cellular cholesterol by mevalonate
      and methyl-beta-cyclodextrin leads to the shift of PGI2 synthase and caveolin-1
      to higher density fractions of the gradient. Biochemical evidence about
      colocalization was supported by the use of a fusion protein glutathione S
      transferase (GST)/caveolin-1, which retained either PGI2s purified from ram
      seminal vesicles or PGI2s present in HUVE cell lysates. Binding of PGI2s to
      caveolin "scaffolding domain" and to C-terminal region was deduced by using full
      length GST--Cav-1, GST--Cav 61--101, and GST C- and N-terminal fusion proteins. A
      double approach based on the usage of filipin as a specific caveolae-disrupting
      agent and antisense oligonucleotides targeting PGI2 synthase mRNA suggests that
      the production of PGI2 in caveolae is likely to be connected to the regulation of
      angiogenesis, at least in vitro.

PMID- 11339823
TI  - Activated macrophages migrate to the subcutaneous tumor site via the peritoneum:
      a novel route of cell trafficking.
AB  - Spontaneous regression of AK-5 tumor in syngeneic hosts reported earlier involves
      the interplay of Th1-type cytokines and cell-mediated immunity. Upon subcutaneous
      transplantation of AK-5 cells, there was accumulation of immune cells in the
      peritoneum, of which macrophages were the predominant type and were found to be
      in a hyperactive state. They released macrophage-derived tumoricidal mediators
      like NO, O2(-), and ONOO(-) which exhibited potent cytotoxic activity against AK
      5 cells in vitro. Interestingly, there was a dramatic disappearance of these
      hyperactive cells from the peritoneal cavity which correlated well with the onset
      of tumor regression at the subcutaneous site. Direct labeling of these cells in
      the peritoneum by the tracking dye PKH26 showed their migration to the tumor
      site. Similarly, frozen tumor sections when scanned under confocal microscope
      clearly exhibited fluorescent macrophages embedded into the tumor.
      Immunohistochemical sections of these intratumoral macrophages showed
      nitrotyrosine residues, indicating their contribution in the free-radical
      mediated AK-5 cell death, thereby leading to successful tumor remission. These
      observations suggest a directional migration of the hyperactivated peritoneal
      population to the tumor site. We have also confirmed the influx of macrophages
      and other immune cells into the peritoneum after sc transplantation of Meth A
      tumor cells in Balb/c mice. Our studies suggest a role for the peritoneal
      compartment in imparting appropriate stimulus to the immune cells prior to their
      participation in the antitumor immune response. These studies suggest a novel
      route of macrophage trafficking via the peritoneum.

PMID- 11339824
TI  - 5-Bromodeoxyuridine suppresses position effect variegation of transgenes in HeLa
      cells.
AB  - An ectopic gene integrated in the host genome is occasionally silenced due to a
      position effect of its adjacent chromatin structure. We found that 5
      bromodeoxyuridine clearly activated such a transgene in HeLa cells. The transgene
      was also activated to various degrees by inhibitors of histone deacetylase, DNA
      topoisomerases, or DNA methyltransferase. The peptide antibiotic distamycin A
      potentiated markedly the effect of 5-bromodeoxyuridine. Transient expression of
      an artificial AT-hook protein termed MATH20 also potentiated its effect although
      significantly activated the transgene alone. Since distamycin A and MATH20 are
      able to displace histone H1 and other DNA-binding proteins bound to specific AT
      rich sequences by a dominant, mutually exclusive fashion, these results suggest
      that 5-bromodeoxyuridine targets such an AT-rich sequence located adjacent to the
      silenced transgene, resulting in chromatin accessibility.

PMID- 11339825
TI  - Selective degradation of the PKC-epsilon isoform during cell death in AKR-2B
      fibroblasts.
AB  - The protein kinase C (PKC) family of serine/threonine protein kinases is involved
      in intracellular signals that regulate growth, differentiation, and apoptosis.
      AKR-2B cells express the PKC isoforms alpha, gamma, epsilon, lambda, mu, und zeta
      (J. Hoppe, R. Schafer, V. Hoppe, and A. Sachinidis, Cell Death Differ. 6, 546
      556). Here we show that during serum starvation only PKC-epsilon was cleaved. An
      N-terminal fragment of 42 kDa remained associated with subcellular components,
      presumably the Golgi apparatus. The C-terminal part (catalytic domain) was
      further degraded and was no longer detectable in vivo. As published before, the
      activation of the DEVDase in AKR-2B cells is prevented by numerous agents like
      PDGF, TPA, and DEVD.cmk (R. Schafer, D. Karbach, and J. Hoppe, Exp. Cell Res.
      240, 28--39). All these agents completely prevented PKC-epsilon cleavage,
      indicating a tight correlation between DEVDase activity and PKC-epsilon cleavage.
      By using recombinant caspase-3 or highly purified DEVDase from cytosolic extracts
      we localized by Edman degradation the cleavage site in recombinant PKC-epsilon to
      asp383 in the hinge region between regulatory and catalytic domains. The
      corresponding tetrapeptide sequences SSPD and SATD for human and mouse PKC
      epsilon, respectively, are unusual for caspase-3. Expression of the catalytic
      domain or of the cleavage-resistant mutant D383A had no effect on cell death in
      AKR-2B cells.

PMID- 11339826
TI  - A heterologous 3-D coculture model of breast tumor cells and fibroblasts to study
      tumor-associated fibroblast differentiation.
AB  - The objective of our study was to establish spheroid cocultures as a valid 3-D in
      vitro model mimicking tumor-fibroblast interactions in scirrhous breast tumors.
      The experimental setup was designed to verify if in cocultures (a) adherence and
      migration reflect the invasive potential of breast tumor cells, (b) breast tumor
      cells induce tumor-associated fibroblast differentiation, and (c) tumor-derived
      fibroblasts better reflect the in vivo situation than normal skin fibroblasts.
      Only one (SK-BR-3) out of five tumor cell types showed extensive fibroblast
      infiltration, MCF-7 cells frequently invaded fibroblast spheroids; BT474, T47D,
      and ZR-75-1 were noninvasive. While tumor cell invasion was independent of
      fibroblast origin, tumor-associated myofibroblast differentiation defined by
      alpha-SMA expression was demonstrated for tumor-derived but not normal skin
      fibroblasts in coculture indicating that (a) tumor cell invasion and
      myofibroblast differentiation are autonomous processes and (b) cocultures with
      tumor-derived fibroblasts resemble advanced stages of desmoplastic carcinomas
      while cocultures with normal skin fibroblasts rather reflect the early tumor
      development. The latter is also implied by fibroblast-associated alterations in
      tumor cell morphology and ECM distribution in the system. By using RNA
      arbitrarily primed PCR and cells isolated from cocultures by fluorescence
      activated and magnetic cell separation, peripheral myelin protein PMP22/SR13 has
      been identified as a novel candidate with potential relevance in the interaction
      between tumor cell and normal fibroblast since PMP22 mRNA was significantly
      reduced in normal skin fibroblasts in coculture with BT474 cells.

PMID- 11339827
TI  - Subcellular localization analysis of the closely related Fps/Fes and Fer protein
      tyrosine kinases suggests a distinct role for Fps/Fes in vesicular trafficking.
AB  - The subcellular localizations of the Fps/Fes and closely related Fer cytoplasmic
      tyrosine kinases were studied using green fluorescent protein (GFP) fusions and
      confocal fluorescence microscopy. In contrast to previous reports, neither kinase
      localized to the nucleus. Fer was diffusely cytoplasmic throughout the cell
      cycle. Fps/Fes also displayed a diffuse cytoplasmic localization, but in addition
      it showed distinct accumulations in cytoplasmic vesicles as well as in a
      perinuclear region consistent with the Golgi. This localization was very similar
      to that of TGN38, a known marker of the trans Golgi. The localization of Fps/Fes
      and TGN38 were both perturbed by brefeldin A, a fungal metabolite that disrupts
      the Golgi apparatus. Fps/Fes was also found to colocalize to various extents with
      several Rab proteins, which are members of the monomeric G-protein superfamily
      involved in vesicular transport between specific subcellular compartments. Using
      Rabs that are involved in endocytosis (Rab5B and Rab7) or exocytosis (Rab1A and
      Rab3A), we showed that Fps/Fes is localized in both pathways. These results
      suggest that Fps/Fes may play a general role in the regulation of vesicular
      trafficking.

PMID- 11339828
TI  - Cripto-1 enhances migration and branching morphogenesis of mouse mammary
      epithelial cells.
AB  - Cripto-1 is an EGF-CFC protein that performs an important role during early
      vertebrate development and is overexpressed in several types of human cancer. In
      the present study mouse EpH4, NMuMG, and TAC-2 mammary epithelial cells that are
      negative for endogenous cripto-1 expression were transfected with the murine
      cripto-1 cDNA. Cripto-1-transfected cell lines exhibited functional and
      physiological differences from the original cell lines including enhanced
      anchorage-independent growth in soft agar (EpH4 cells), growth in serum-free
      medium, increased proliferation, and formation of branching, duct-like structures
      when grown in a three-dimensional collagen type I matrix. Furthermore, cripto-1
      expressing cell lines showed elevated migration in vitro in Boyden chamber and
      wound-healing assays. These results indicate that cripto-1 can function through
      an autocrine pathway that enables mammary epithelial cells to undergo an
      epithelial to mesenchymal transition.

PMID- 11339829
TI  - Contrasting roles of p57(KIP2) and p21(WAF1/CIP1/SDI1) in transplanted human and
      bovine adrenocortical cells.
AB  - Cell transplantation provides a way to compare the regulation of cell
      proliferation in the same cell type in cell culture and in a vascularized tissue
      structure in a host animal. The cyclin-dependent kinase inhibitors p57(KIP2),
      p21(WAF1/CIP1/SDI1) and p27(KIP1) have been extensively studied in cell culture
      but their role in growth control in tissues is less well understood. In the
      present experiments we compared the behavior of cell cycle inhibitors in human
      and bovine adrenocortical cells in culture and following cell transplantation in
      scid mice. p57 was expressed in the majority of cells in the intact human adrenal
      cortex. However, double immunofluorescence showed that cells that are in the cell
      cycle are p57(-) adrenocortical cells, p57 and p27 levels were not affected by
      inhibition of growth at high cell density, whereas p21 was higher in dividing
      than growth-inhibited cells. However, p21 was also high in senescent
      adrenocortical cells. After transplantation of human adrenocortical cells in scid
      mice, p57 and p27 were observed in most cells in the transplant tissue. Over time
      the number of p21(+) cells decreased greatly in human adrenocortical cells, but
      not in bovine adrenocortical cells. This difference correlated with lower levels
      of cell division (assessed by Ki-67 or incorporation of bromodeoxyuridine) in the
      human cells in transplant tissues in comparison to bovine cells. The differences
      between human and bovine cells were observed both when cells were transplanted
      beneath the kidney capsule and when cells were injected subcutaneously in
      collagen gel. We conclude that the behavior of p57, but not p21, is consistent
      with a role as a physiological mediator of proliferative quiescence in the
      adrenal cortex. The high level of p21 in dividing adrenocortical cells in
      culture, and in bovine adrenocortical cells in transplant tissues, may be a
      response to conflicting positive and negative growth influences. Cells may enter
      the cell cycle under the influence of a strong positive mitogenic signal, but
      coexisting negative growth stimuli trigger a p21-dependent block to further
      progression through the cell cycle. This model suggests that bovine
      adrenocortical cells respond to positive growth stimuli in transplant tissues but
      human cells lack this response.

PMID- 11339830
TI  - EAT/mcl-1 expression in the human embryonal carcinoma cells undergoing
      differentiation or apoptosis.
AB  - Differentiation and apoptosis are precisely regulated events in early
      embryogenesis. Retinoic acid-induced differentiation in the embryonal carcinoma
      (EC) cell line NCR-G3 triggers concurrent induction of apoptosis. Using this
      system, which serves as a model of early embryogenesis, the expression of various
      bcl-2-related genes was analyzed as these genes display either positive or
      negative regulatory effects on apoptosis. EAT/mcl-1, an antiapoptotic bcl-2
      related gene and immediate early gene, was dramatically expressed at an early
      stage of NCR-G3 differentiation. Bcl-xL, another antiapoptotic gene, was induced
      at a middle stage of differentiation and then gradually decreased to basal level.
      Expression of Bax, a proapoptotic molecule, was detected at a high level and
      remained relatively constant. Meanwhile, Bcl-2 and Bcl-xS were below detectable
      levels throughout the various stages of differentiation. As the balance of bcl-2
      genes is a crucial regulatory step in apoptosis, the results suggest that EAT and
      Bax likely regulate apoptosis in the early stages of differentiation. In later
      stages of differentiation, down-regulation of EAT was found to coincide with a
      gradual increase in apoptosis of NCR-G3 cells. Furthermore, use of the monoclonal
      antibody (3A2) specific to EAT revealed that EAT is localized to the outer
      mitochondrial membrane in human EC cells. In addition, EAT immunoreactivity was
      not detected in apoptotic NCR-G3 cells while it was observed in nearly all viable
      cells. The findings suggest that rapid induction of EAT may prevent NCR-G3 cells
      from undergoing apoptosis, thereby supporting viability at the early stage of
      differentiation.

PMID- 11339831
TI  - Cell proliferation and CD11b expression are controlled independently during HL60
      cell differentiation initiated by 1,25 alpha-dihydroxyvitamin D(3) or all-trans
      retinoic acid.
AB  - When 1 alpha,25-dihydroxyvitamin D(3) (D(3)) induces HL60 cells to differentiate
      to monocytes, a burst of approximately three shortened cell cycles ("maturation
      divisions") precedes exit from cell cycle and completion of maturation. Here we
      show that similar maturation divisions occur during neutrophil differentiation
      induced by all-trans-retinoic acid (ATRA), but without shortening of the cell
      cycle. Both ATRA and D(3) initiate these maturation divisions as cells pass
      through a "window of sensitivity" during early G1. We also investigated whether
      the initiation of maturation divisions and of the expression of CD11b, an early
      expressed maturation marker, are linked. Cells treated with D(3) or ATRA start to
      express CD11b after 9--14 h, before completing the first maturation division.
      Elutriation was used to isolate small HL60 cells (almost all in G1) and larger
      cells (in G1 and S phases) from unsynchronized populations. When these were
      cultured with D(3) or ATRA, most reentered cycle synchronously, multiplied, and
      differentiated. Following D(3) treatment, the G1-enriched small cells expressed
      CD11b slightly faster than unsynchronized cultures or fractions dominated by late
      G1 cells and/or S phase cells. D(3)-induced CD11b expression occurred at a
      similar rate even in G1 cells that were held at the G1/S boundary by thymidine.
      In conclusion, changes in the control of the cell cycle that characterize the
      onset of monocytic and neutrophil differentiation are only triggered in early G1,
      but CD11b expression can be initiated from most points in the cell cycle.
      Differentiating agents must therefore regulate the proliferation and the
      maturation of differentiating myeloid cells by mechanisms that are at least
      partly independent.

PMID- 11339832
TI  - RasG regulates discoidin gene expression during Dictyostelium growth.
AB  - Activated rasG, rasG(G12T), was expressed in Dictyostelium cells under the
      control of the folate-repressible discoidin promoter (pVEII-rasG(G12T)) and found
      to have a unique pattern of expression when cells were transferred to folate
      deficient media: an initial increase of RasG(G12T) resulting from the removal of
      folate, followed by a rapid decline while cells were still in the early
      exponential phase of growth. Discoidin levels were considerably lower and
      declined more rapidly in the pVEII-rasG(G12T) transformant than they did in the
      wild type, suggesting that RasG(G12T) represses discoidin expression. This was
      independently confirmed by placing the rasG(G12T) gene under the control of the
      ribonucleotide reductase (rnrB) promoter. Exposure of cells to 10 mM methyl
      methanesulfonate (MMS) rapidly generated RasG(G12T) and this was accompanied by
      an equally rapid decrease in discoidin mRNA levels. rasG null cells also
      contained decreased levels of discoidin under all conditions tested, indicating
      that RasG is essential for optimum discoidin expression. However, rasG null cells
      showed normal regulation of discoidin expression in response to PSF, CMF, folate,
      bacteria, and axenic media, indicating that RasG is not necessary for any of
      these responses. These results reveal a role for RasG in regulating discoidin
      gene expression and add a further level of complexity to the regulation of the
      discoidin promoter.

PMID- 11339833
TI  - Caveolin-1 and a 29-kDa caveolin-associated protein are phosphorylated on
      tyrosine in cells expressing a temperature-sensitive v-Abl kinase.
AB  - Caveolin-1 was originally identified as a tyrosine-phosphorylated protein in v
      Src-transformed cells and it was suggested that phosphorylation of this protein
      could mediate transformation by the tyrosine kinase class of oncogenes (J. R.
      Glenney, 1989, J. Biol. Chem. 264, 20163--20166). We found that caveolin-1 is
      also phosphorylated on tyrosine in v-Abl-transformed cells. In fact, caveolin-1
      and a caveolin-associated protein of 29 kDa are among the strongest
      phosphotyrosine signals detected in the Abl-expressing cells. In addition, v-Abl
      shows a preferential phosphorylation of caveolin-1 and the 29-kDa caveolin
      associated protein over other proteins in the caveolin-enriched Triton-resistant
      cell fraction. These data indicate that caveolin-1 and the 29-kDa caveolin
      associated protein may be preferred substrates of the Abl kinase. Caveolin-1 is
      phosphorylated at tyrosine 14 in v-Abl-expressing cells as has been observed
      previously in v-Src-expressing cells. However, using a temperature-sensitive
      allele of v-Abl (ts120 v-Abl) we provide evidence that caveolin-1 phosphorylation
      is not sufficient to mediate the loss of caveolin expression or loss of cell
      adhesion induced by v-Abl.

PMID- 11339834
TI  - Effects of pdgf-bb on rat dermal fibroblast behavior in mechanically stressed and
      unstressed collagen and fibrin gels.
AB  - The dose-response effects of platelet-derived growth factor BB (PDGF-BB) on rat
      dermal fibroblast (RDF) behavior in mechanically stressed and unstressed type I
      collagen and fibrin were investigated using quantitative assays developed in our
      laboratory. In chemotaxis experiments, RDFs responded optimally (P < 0.05) to a
      gradient of 10 ng/ml PDGF-BB in both collagen and fibrin. In separate
      experiments, the migration of RDFs and the traction exerted by RDFs in the
      presence of PDGF-BB (0, 0.1, 1, 10, or 100 ng/ml) were assessed simultaneously in
      the presence or absence of stress. RDF migration increased significantly (P <
      0.05) at doses of 10 and 100 ng/ml PDGF-BB in collagen and fibrin in the presence
      and absence of stress. In contrast, the effects of PDGF-BB on RDF traction
      depended on the gel type and stress state. PDGF-BB decreased fibroblast traction
      in stressed collagen, but increased traction in unstressed collagen (P < 0.05).
      No statistical conclusion could be inferred for stressed fibrin, but increasing
      PDGF-BB decreased traction in unstressed fibrin (P < 0.05). These results
      demonstrate the complex response of fibroblasts to environmental cues and suggest
      that mechanical resistance to compaction may be a crucial element in dictating
      fibroblast behavior.

PMID- 11339835
TI  - Hyaluronidase can modulate expression of CD44.
AB  - CD44 is a family of transmembrane glycoproteins with multiple isoforms generated
      by alternative exon splicing of a single gene. CD44 and its variants are
      expressed on a wide variety of cells including cancer cells. The mechanisms by
      which splice variant exons are selected are unknown. The presence of hyaluronan
      in the environment of the cell appears to influence that selection process. The
      expression of particular splice variants of CD44 as well as the simultaneous
      presence of hyaluronan is important for motility, invasion, and the metastatic
      spread of some tumors. The influence of hyaluronidase digestion on the expression
      of CD44 in human cancer cell lines was examined. CD44 isoforms containing
      alternatively spliced exons were sensitive to hyaluronidase digestion in all
      lines examined, but differences between cell lines were observed. Expression of
      CD44s, the standard form, was resistant to digestion in two of three cell lines.
      A tentative model was formulated proposing that CD44 isoforms containing splice
      variants are unstable, requiring the continuous presence of ligand for
      expression. CD44s is relatively more stable, not requiring the continuous
      presence of hyaluronan. Additionally, a number of new CD44 variant isoforms, not
      previously observed, were identified.

PMID- 11339836
TI  - A new alternatively spliced transcript of the mouse connexin32 gene is expressed
      in embryonic stem cells, oocytes, and liver.
AB  - The rodent gap junction protein connexin32 (Cx32) is highly expressed in
      hepatocytes, less abundantly in Schwann cells and oligodendrocytes, and at low
      levels in the early mouse embryo. In both hepatocytes and Schwann cells, Cx32
      expression is directed by alternative promoter regions (P1 and P2) which activate
      differently spliced transcript isoforms. Here we describe a third Cx32 transcript
      isoform expressed in embryonic cells, oocytes, and liver. Using competitive
      polymerase chain reaction, we have found that this new Cx32 transcript containing
      exon 1A is 200-fold less abundant in liver than the Cx32 isoform with exon 1. In
      mouse oocytes, the exon 1A-containing Cx32 transcript is exclusively expressed.
      Immunoblot analyses revealed no Cx32 protein expression in embryonic stem cells,
      whereas it has previously been demonstrated in oocytes. When the putative Cx32
      promoter region upstream of exon 1A was cloned before the lacZ reporter gene,
      transient transfection yielded weak expression in embryonic stem cells. Our
      results suggest that the exon 1A-containing Cx32 isoform is likely to be
      inherited as an oogenetic product but not translated during early embryogenesis.

PMID- 11339837
TI  - c-Mos proteolysis is independent of the CA(2+) rise induced by 6-DMAP in Xenopus
      oocytes.
AB  - In Xenopus oocytes, metaphase II arrest is due to a cytostatic factor (CSF) that
      involves c-Mos, maintaining a high MPF (cdk1/cyclin B) activity in the cell. At
      fertilization, a rise in intracellular calcium triggers the proteolysis of both
      cyclin B and c-Mos. The kinase inhibitor 6-dimethylaminopurine (6-DMAP) is also
      able to release matured Xenopus oocytes from metaphase II block. This is
      characterized by c-Mos proteolysis without degradation of cyclin B. We
      hypothesized that 6-DMAP induced an increase in intracellular calcium. Using the
      calcium-sensitive fluorescent dye Fura-2, we observed a systematic increase in
      intracellular calcium following 6-DMAP application. In matured oocytes previously
      microinjected with the calcium chelator BAPTA, no calcium changes occurred after
      6-DMAP addition; however, c-Mos was still proteolysed. In oocytes at the GVBD
      stage, c-Mos proteolysis occurred in response to 6-DMAP but not to calcium
      ionophore treatment. We suggest that c-Mos proteolysis is rather controlled by a
      phosphorylation-dependent process.

PMID- 11339838
TI  - Prosomes form sarcomere-like banding patterns in skeletal, cardiac, and smooth
      muscle cells.
AB  - Prosomes (20S proteasomes) constitute the catalytic core of the 26S proteasomes,
      but were first observed as factors associated with unstranslated mRNA. Recently,
      their RNase activity was discovered together with the fact that their proteolytic
      function is dispensable in adapted human cells. By indirect immunofluorescence
      using monoclonal antibodies, we demonstrate as a general phenomenon, regular
      intercalation of specific types of prosomes into the sarcomeric structure of all
      types of striated muscle. Surprisingly, in cultured smooth muscle cells without
      sarcomeric organization, some prosomes also form regular striations in extended
      projections of cytoplasmic regions. The significance of their sarcomeric
      distribution is not understood as yet, but the pattern we observe is very similar
      to that shown by others for muscle-specific mRNAs, identified by in situ
      hybridization, and that of the cognate proteins. A role of prosomes in the
      cotranslational assembly of the myofibrillar proteins is suggested, since
      prosomes organize into pseudo-sarcomeric patterns prior to formation de novo of
      the actin-myosin arrangement.

PMID- 11339839
TI  - Obsessive-compulsive disorder: a neuronal membrane phospholipid hypothesis and
      concomitant therapeutic strategy.
AB  - Obsessive-compulsive disorder (OCD) is briefly characterized and several of the
      hypothesized neuroanatomical and neurochemical substrates of this etiologically
      heterogeneous syndrome are indicated as well as similarities among OCD,
      schizophrenia and bipolar disorder. A neuronal membrane phospholipid hypothesis
      is proposed for OCD analogous to those developed for schizophrenia by Horrobin et
      al. and for bipolar disorder by Stoll et al. Essential fatty acid (EFA) dietary
      supplementation has shown some efficacy in treating schizophrenia and bipolar
      disorder patients and should also be considered for OCD. Supporting this, a case
      report is presented of a subject with OCD who developed comorbid paresthesia, for
      whose latter condition a regimen of ibuprofen was instituted. Thirteen weeks
      thereafter subject's OCD symptomatology had declined by 40% (YBOC scale) from
      baseline. Inasmuch as ibuprofen and numerous other non-steroidal anti
      inflammatory drugs (NSAIDS) block brain neuronal prostaglandin synthase (several
      also inhibiting phospholipases A(2)and C), thereby reducing catabolism of
      neuronal membrane arachidonic acid, the ibuprofen apparently increased the
      integrity of subject's neuronal membranes, as would likely also be the case with
      EFA dietary supplementation. This OCD NSAID-EFA therapy concept should be further
      tested by seeking other OCD subjects, especially from arthritis and rheumatism
      practices (where NSAIDS are routinely employed) and medical record data banks, as
      OCD has an estimated worldwide population lifetime prevalence of 1% to 3% and at
      least a subset of OCD patients might possibly benefit.

PMID- 11339840
TI  - Hind-limb/hind-quarter vascular resistance and blood flow changes: possible
      intrinsic renin--angiotensin system involvement.
AB  - For many years there was a general belief that the enzyme renin, having been
      secreted into the circulation by the kidney in response to appropriate stimuli,
      initially generates the inactive decapeptide angiotensin I in the bloodstream.
      This is then converted to the biologically active octapeptide angiotensin II by
      angiotensin converting enzyme on or near, vascular surface receptors both in the
      lungs and in the organs supplied by the systemic circulation. The results of
      various investigations have, however, latterly led to the conclusion that the
      overall system is widely distributed throughout the vasculature with the local
      intracellular formation of angiotensin II. In this review the reckoned intrinsic
      renin-angiotensin activity in hind-limb/hind-quarter is discussed with particular
      regard to the widespread use of radioimmunoassay, together with a consideration
      of other factors, more especially ACE inhibition, affecting the relevant regional
      vascular resistance and blood flow.

PMID- 11339841
TI  - Microecology, bacterial vaginosis and probiotics: perspectives for
      bacteriotherapy.
AB  - Probiotics enriched in lactobacilli have been proposed as an effective and
      alternative tool to antibiotics for the treatment of bacterial vaginosis. The
      protective role of H(2)O(2)-producing lactobacilli has been strongly emphasized,
      but no clear-cut correlation appears to link the metabolic characteristics of
      administered lactobacilli with the clinical impact of probiotic therapy. On
      account of our review of basic mechanisms involved in bacterial vaginosis, we
      suggest that lactobacilli with an elevated arginine deiminase activity could have
      a greater therapeutic potential than strains producing only H(2)O(2). Preliminary
      results from our laboratory have demonstrated that treatment with probiotics
      containing arginine deiminase-positive lactobacilli improves clinical symptoms
      and is paralleled by a significant decline of polyamine levels in vaginal
      microenvironment. This is of outstanding interest due to the central role of
      polyamines in the pathogenesis of bacterial vaginosis. We should critically
      rethink, against this perspective, the use of probiotics for the treatment of
      affected women.

PMID- 11339842
TI  - Comments on the unreasonable effectiveness of the biological and especially
      medical sciences.
AB  - About 50 years ago it was pointed out by Dr. Eugene Wigner that applications of
      mathematics to a wide range of physical problems were inexplicably effective in
      both their immediate practical results and predictive power. The reasons for this
      remain elusive. In a loosely analogous sense, parallels can be drawn between such
      an effectiveness and the evolving power of the biological sciences, leading to
      the accomplishment of many practical and theoretical goals. We consider some of
      the similarities and differences that distinguish these two modalities with which
      certain features of physical reality are apprehanded, analyzed and manipulated.

PMID- 11339843
TI  - A theory of cellular-function pathology: further development of Virchow's theory
      of cellular pathology.
AB  - A new theory of pathology is introduced. The human cell is an organism in itself.
      It fulfills both cell-oriented and organism-oriented functions. Impairment of
      either one of these functions may lead to disease. This means that a structural
      lesion of a cell is not a sole and necessary cause of the beginning of disease.
      When a cell-oriented function is impaired the cell suffers, but the overt
      symptoms at the organ-organism level might be absent for a very long time. This
      is how a chronic asymptomatic disease starts. Measures of prophylaxis, diagnosis,
      and treatment should be centered upon maintenance and restoration of a balance
      between the cell-oriented and organism-oriented cellular functions.

PMID- 11339844
TI  - Computerized detection of clustered microcalcifications: a modular approach with
      non-linear filters.
AB  - The ideal computerized mammogram processing system still needs to be developed.
      In order to achieve maximum flexibility we suggest a modular scheme, dividing the
      processing sequence into functionally autonomous modules. This paper provides a
      general scheme for detection and/or automated recognition of microcalcifications.
      Some modules that perform ROI selection are introduced, using special non-linear
      filters designed for microcalcification detection. A first type of filter selects
      pixels with specific statistical local features, as compared to the local mean.
      Among these, only pixels satisfying particular constraints on the local standard
      deviation are kept. Another type of filter then checks the local mean values of
      gradient components, so that sharp variations, unrelated to small close objects,
      can be eliminated. The scheme thus applies different non-linear filters in
      combination, making precise identification of clustered microcalcifications
      possible. This modular approach seems greatly to simplify system maintenance and
      consistency, as well as affording a comparison of different processing techniques
      and parameters.

PMID- 11339845
TI  - Redefining 'self': the role of microflora (commensals) mismatch in the
      development of GvHD after allogeneic stem cell transplantation and some possible
      remedies.
AB  - The discovery of human leukocyte antigen (HLA) molecules and their role in
      allorecognition has facilitated the initiation of allogeneic stem cell
      transplantation in human beings. HLA mismatch to a large extent explains the
      phenomenon of graft rejection and graft versus host disease (GvHD). Incidence of
      GvHD even in syngeneic transplants suggests a role for extra genetic factors in
      the causation of GvHD. We hereby propose a hypothesis that the definition of
      'self' (in the immunological sense) should be broadened to include both
      genetically determined molecules (e.g. HLA) and the microbial flora that colonize
      an individual. This hypothesis explains several observations about GvHD which can
      not fully be accounted for by the HLA mismatch theory and gives some clues
      towards circumventing GvHD.

PMID- 11339846
TI  - The natriuretic peptides: universal volume controllers.
AB  - Since the discovery of the natriuretic effect of atrial natriuretic peptide
      (ANP), a family of other natriuretic peptides similar to ANP were isolated,
      including atriopeptin, vessel dilator, long-acting natriuretic peptide,
      urodilatin, and brain natriuretic peptide (BNP) to name a few. ANP was noted to
      possess natriuretic and diuretic properties that controlled increases in
      intravascular volume. ANP was also found to be elevated in conditions of
      increased intraocular pressure and biliary obstruction. BNP was found to be
      elevated in conditions of increased intracranial pressure, pointing towards its
      role in controlling cerebrospinal fluid volume. While at the cellular level, ANP
      controlled individual cell size. This makes the natriuretic peptides not only
      controllers of intravascular volume, but also modulators of a myriad of cavity
      volumes down to the control of individual cell volume.

PMID- 11339847
TI  - Metabolic bioenergy homeostatic disruption: a cause of anorexia nervosa.
AB  - We believe anorexia nervosa is the result of a disruption in bioenergy
      homeostasis induced by lipid dysregulation. This disruption has two major
      determinants: (1) a biological predisposition to primary multihormonal disharmony
      linked to post-pubertal growth and development; and (2) an acquired abnormal
      lipid-induced loop operation precipitated by inappropriate diet. We present a
      step-by-step model describing the cascade of disorders that culminates in
      anorexia nervosa: defective digestion and absorption of essential fatty acids;
      diversion of lipids from adipose cells into bloodstream; defective carbohydrate
      and lipid metabolism which modifies the blood brain barrier; neuroendocrine
      membrane alteration causing severe endocrine impairment; changes in the negative
      feedback mechanism which escalate the body's use of bioenergy; derangement of the
      appetite center which causes a constant sensation of satiety; replacement of the
      correct body image with the premorbid one that encourages poor judgement
      concerning food intake and self-support. The loop-like nature of this mechanism
      perpetuates the disease.

PMID- 11339849
TI  - Therapeutic potential of N-acetylcysteine in age-related mitochondrial
      neurodegenerative diseases.
AB  - Increasing lines of evidence suggest a key role for mitochondrial damage in
      neurodegenerative diseases. Brain aging, Parkinson's disease, Alzheimer's
      disease, Huntington's disease and Friedreich's ataxia have been associated with
      several mitochondrial alterations including impaired oxidative phosphorylation.
      Mitochondrial impairment can decrease cellular bioenergetic capacity, which will
      then increase the generation of reactive oxygen species resulting in oxidative
      damage and programmed cell death. This paper reviews the mechanisms of N
      acetylcysteine action at the cellular level, and the possible usefulness of this
      antioxidant for the treatment of age-associated neurodegenerative diseases.
      First, this thiol can act as a precursor for glutathione synthesis as well as a
      stimulator of the cytosolic enzymes involved in glutathione regeneration. Second,
      N-acetylcysteine can act by direct reaction between its reducing thiol group and
      reactive oxygen species. Third, it has been shown that N-acetylcysteine can
      prevent programmed cell death in cultured neuronal cells. And finally, N
      acetylcysteine also increases mitochondrial complex I and IV specific activities
      both in vitro and in vivo in synaptic mitochondrial preparations from aged mice.
      In view of the above, and because of the ease of its administration and lack of
      toxicity in humans, the potential usefulness of N-acetylcysteine in the treatment
      of age-associated mitochondrial neurodegenerative diseases deserves
      investigation.

PMID- 11339848
TI  - Autism: a novel form of mercury poisoning.
AB  - Autism is a syndrome characterized by impairments in social relatedness and
      communication, repetitive behaviors, abnormal movements, and sensory dysfunction.
      Recent epidemiological studies suggest that autism may affect 1 in 150 US
      children. Exposure to mercury can cause immune, sensory, neurological, motor, and
      behavioral dysfunctions similar to traits defining or associated with autism, and
      the similarities extend to neuroanatomy, neurotransmitters, and biochemistry.
      Thimerosal, a preservative added to many vaccines, has become a major source of
      mercury in children who, within their first two years, may have received a
      quantity of mercury that exceeds safety guidelines. A review of medical
      literature and US government data suggests that: (i) many cases of idiopathic
      autism are induced by early mercury exposure from thimerosal; (ii) this type of
      autism represents an unrecognized mercurial syndrome; and (iii) genetic and non
      genetic factors establish a predisposition whereby thimerosal's adverse effects
      occur only in some children.

PMID- 11339850
TI  - Alpha helix capping and the conformation of threonine.
AB  - The amino acid threonine contains two chiral carbons and thus can exist in four
      possible conformations. However, only a single conformation (2S, 3R) of threonine
      is incorporated in proteins by the cellular translation material. The
      conformation at the alpha carbon (carbon 2) is the same as that of the other
      amino acids in biological proteins, and there is no explanation for why this
      enantiomer was selected. Further, there is no explanation for the choice of
      conformation at the 3 carbon in threonine. Here, I suggest that the preferential
      ability of (2S, 3R) threonine over the (2S, 3S) enantiomer to participate in
      alpha helix capping interactions may have led to the selection of the (2S, 3R)
      conformation.

PMID- 11339851
TI  - Psychosocial interventions and cancer patients: psychological and immune
      responses may depend on cancer type.
AB  - Psychological and immunological responses of cancer patients to a psychosocial
      intervention program will be assessed over time. Previously it has been proposed
      that there are two large divisions in cancer histology (type I and II) and that
      the psychobiology of patients will vary accordingly.

PMID- 11339852
TI  - The Th2-hypothesis of schizophrenia: a strategy to identify a subgroup of
      schizophrenia caused by immune mechanisms.
AB  - Immunologic findings in schizophrenia have been described for decades, but it was
      not possible to identify a pathogen until now. Most of these studies report
      immune abnormalities in a group of the investigated patients, but a distinct
      subgroup of schizophrenia with immune-related pathology has still not been
      characterized. In this paper we have integrated the most important immunologic
      data in schizophrenia research and hypothesize a shift to Th2-like immune
      reactivity in a subgroup of schizophrenic patients. Besides the immunological
      abnormalities, this subgroup is further characterized by more pronounced negative
      symptoms and poor therapy outcome. There is evidence that this subgroup might be
      caused by a prenatal viral infection.

PMID- 11339853
TI  - Downregulation of a tumor promotion immune response via induction of oral
      tolerance towards tumor-associated-antigens: can we 'eat the tumor'?
AB  - The mechanism by which hepatocellular carcinoma (HCC) develops and the role of
      the hepatitis B virus (HBV) in inducing tumors, are not yet well understood.
      Patients persistently infected with HBV tend to have a defective immune response
      against the virus, which fails to clear the virus and also induces liver injury.
      This defective response may also have an inducible effect on the virus and on
      cells that express HBV antigens, as well as play a role in the growth of
      neoplasm. It is possible that one of the mechanisms of tumor growth is related to
      a deviant immune response towards viral or tumor associated antigens. We describe
      two responses against the tumor. A 'good' response that would suppress the tumor
      and a 'bad' response that would promote it and theorize that the net balance
      between 'bad' and 'good' responses of the immune system towards a cancerous cell
      and/or antigen will predict whether a tumor grows or is suppressed. Oral
      tolerance involves the induction of immunological hyporesponsiveness towards
      specific antigens. It was shown that oral tolerance induces antigen-specific
      immune suppression towards tumor-associated-antigens by feeding of HBV or other
      tumor proteins. We hypothesize that induction of immune tolerance towards tumor
      associated antigens will suppress the immune response towards these antigens,
      thus reducing the 'bad' response. The proposed new treatment strategy would
      redirect the focus from augmenting anti-tumor immune responses to inducing host
      tolerance towards the tumor.

PMID- 11339854
TI  - Earth's orbital chirality and driving force of biomolecular evolution.
AB  - In our recent studies, it has been suggested that both symmetry breaking
      (violation) and biological rhythms could be caused by the natural rhythmic right
      handed helical force field produced by the Earth's orbital chirality (EOC) (1-
      3). In this essay, according to the further theoretical and experimental studies,
      it was suggested that the natural EOC force field could serve as the diving force
      of biomolecular evolution via the chiral interactions. In addition, the following
      suggestions also were pointed out: (1) The EOC force field could cause the origin
      of non-coding repetitive DNA sequences ('Junk DNA') to increase the genomes
      stability and complexity; (2) The EOC force field could increase the structural
      order of biological systems via the biomolecular EOC stabilization energy
      effects; (3) The biological information could be spontaneously produced by the
      chiral interactions of the protogenes with the EOC force field.

PMID- 11339855
TI  - Choriodecidual inflammatory syndrome (CoDIS) is the leading, and under
      recognised, cause of early preterm delivery and second trimester miscarriage.
AB  - Severe preterm birth (delivery before 32 completed weeks of gestation), with or
      without preterm premature rupture of the membranes (PPROM), remains the leading
      cause of perinatal mortality. It is proposed that localized inflammation of the
      chorion and decidua in the membranes immediately above the internal cervical os,
      with or without amniotic cavity infection and inflammation, is the leading, but
      under recognised, cause of second trimester miscarriage and severe preterm
      delivery. The term 'CoDIS' (choriodecidual inflammatory syndrome), may provide a
      better understanding of the underlying pathophysiology than currently used
      terminology which over emphasizes the importance of overt intra-amniotic
      infection as opposed to localized extra-amniotic inflammation which stimulates
      uterine evacuation.

PMID- 11339856
TI  - Thoraco-pulmonary disproportion, scoliosis, kyphosis, frozen spine, dystonia and
      other muscular disorders, including those of the universal contractile chambers.
AB  - A nervous system with muscle to do its bidding elevates the animal above the
      plant world. Much of what happens in the body, good or bad, involves muscular
      action. A muscle may underact or quit. It may also overact, even to the point of
      rupturing. Since muscles come in pairs, a muscular action is a double effect
      requiring coordination between the mated muscles. Cooperation between paired
      muscles is sometimes lacking and both muscles contract or relax simultaneously so
      the desired effect does not happen, or destructive conflict develops which leads
      to various secondary disorders and chain reactions. Muscles react
      favorably/unfavorably to whatever stimuli they get.

PMID- 11339857
TI  - Can we identify genes for susceptibility to diabetic microangiopathies using
      stroke-prone spontaneously hypertensive rat models?
AB  - The aortic biochemical properties are reported to be altered in stroke-prone
      spontaneously hypertensive rats (SHR-SPs) as a result not only of the accelerated
      accumulation of advanced glycation end products (AGEs) in thoracic aortae but
      also of primary defects. There is a growing body of evidence that reactive oxygen
      species (ROS) are involved in the formation of AGEs. We propose here a novel
      hypothesis that SHR-SPs are the strain that genetically produce more ROS
      generations. Since ROS formations and AGE accumulations play central roles in the
      pathogenesis of diabetic microvascular complications, SHR-SPs might be more
      susceptible to vascular complications when induced to be diabetic. To reveal new
      genes involved in susceptibility to diabetic microangiopathies through the study
      of these animal models might be a valuable strategy to develop novel therapeutic
      approaches.

PMID- 11339858
TI  - The rise in the atmospheric concentration of carbon dioxide and the effects on
      human health.
AB  - The potential effects on the health of future generations of humans, and other
      mammals arising from the increase in the concentration of carbon dioxide in the
      atmosphere, resulting from the use of large amounts of fossil fuels by
      industrialized societies, is considered. It is concluded that the change in the
      gaseous composition of the atmosphere will lead to a decline in the health of
      humans and may well lead to serious population reductions.

PMID- 11339859
TI  - Total immediate ancestral longevity (TIAL) score as a longevity indicator: an
      analysis on Einstein and three of his scientist peers.
AB  - The total immediate ancestral longevity (TIAL) score was first introduced by
      Raymond Pearl as a convenient parameter for quantitating human longevity. TIAL is
      the summed ages at death of the six immediate ancestors (namely parents and four
      grandparents) of a propositus. In this communication, I present the calculations
      of TIAL score for Einstein (1879--1955) and three of his scientist peers, namely
      Charles Darwin (1809--1882), Irene Joliot Curie (1897--1956) and Aage Bohr (1922-
      ). The TIAL scores for Einstein, Darwin, Irene Curie and Aage Bohr were 390, 378,
      372 and 436 respectively. These are markedly lower than 477 reported for Jeanne
      Calment, the French woman who died in 1997 at the oldest authenticated age of 122
      years and 164 days. I conclude that the TIAL score is a convenient and easily
      quantifiable longevity parameter which anyone interested in determining his or
      her longevity can use to estimate a tentative number. More light could be shed on
      the worth of the TIAL score as a longevity indicator, if additional data on the
      TIAL scores of royalty and celebrities (for whom verified genealogical data are
      available) are reported.

PMID- 11339860
TI  - Intra-monocyte pathogens delineate autism subgroups.
AB  - Immune panels of many autism-spectrum children reveal signs of atypical
      infections and shifted cell counts. In conjunction with trait-related cerebral
      hypometabolism and hypoperfusion, these findings suggest a hypothesis: Several
      autism-spectrum subgroups derive from intra-monocyte pathogens such as measles
      virus, cytomegalovirus, human herpesvirus 6, and Yersinia enterocolitica.
      Furthermore, with much inter-child variation, their effects manifest as
      diminished hematopoiesis, impaired peripheral immunity, and altered blood-brain
      barrier function often accompanied by demyelination. In some such children, one
      or more of these pathogens persists as a chronic-active, seemingly subclinical
      infection etiologically significant to the child's autistic traits. Within these
      subgroups, immune impairments and atypical infections may be treatable.

PMID- 11339861
TI  - Clostridial constipation's broad pathology.
AB  - Clostridia are normally found in the healthy colon, where their numbers are kept
      in check by other bacteria. However, when they establish themselves in the ileum
      they become formidable foes. They produce medium-length fatty acids that increase
      water absorption, causing hypertension and drying up the feces, causing
      constipation.Furthermore, they can deconjugate bile (impaired fat absorption),
      metabolyze tryptophan (the most scarce of the essential amino acids), digest
      fiber (so that the more fiber the patient takes, the more the constipation is
      exacerbated), digest lecithin, produce carcinogenic metabolites and copious
      amounts of extremely foul smelling gas, etc. They can also prevent vitamin B12
      absorption in the ileum, causing anemia. The synthetic sugar lactulose, which can
      only be digested by lactobacilli, can help displace the clostridia and resolve
      the constipation by causing the lactobacilli to produce short fatty acids that
      have the opposite effect to that of the medium fatty acids produced by clostridia
      and their accomplices: they cause water retention in the intestines.

PMID- 11339862
TI  - Smoking and intervertebral disc degeneration.
AB  - Cigarette smokers have an increased risk of low back pain which may be caused by
      disc degeneration and spinal instability, for example. Ischemia, apoptosis,
      faulty synthesis of disc macromolecules, and an imbalance between disc matrix
      proteinases and their inhibitors may be involved in the pathogenesis of disc
      degeneration. Along with degeneration, the primary avascular disc turns vascular.
      There is some evidence that disc degeneration of cigarette smokers is of more
      severe degree than that of non-smokers.Cigarette-smoking increases serum
      proteolytic activity by releasing proteolytic enzymes from neutrophils in
      alveolar capillaries, and by inhibiting the activity of alpha-1-antiprotease, the
      most potent protease inhibitor. We hypothesize that the high serum proteolytic
      activity of cigarette-smokers gets access to a previously degenerated
      neovascularized disc and speeds up the degerative process. The increased
      proteolytic activity may also weaken the spinal ligaments resulting in spinal
      instability. These processes may explain the increased risk of low back pain of
      cigarette smokers.

PMID- 11339863
TI  - Presynaptic vesicles, exocytosis, membrane fusion and basic physical forces.
AB  - The theoretical hypothesis is presented trying to explain the vesicle release
      from presynaptic nerve ending and membrane fusion. This theoretical concept
      implies only essential physical forces such as electrostatic force and surface
      tension force. Transmembrane resting potential of approximately -70 to -80 mV
      means that the intracellular fluid is electronegative in comparison with
      extracellular one. In this concept it is supposed that the inner and outer lipid
      layer of the membrane also have different electrostatic charges. Presynaptic
      vesicles are made from cell membrane by endocytic process through which the
      vesicle loses the contact with cell membrane. Also, during the endocytic process,
      the inner lipid layer of the cell membrane becomes the outer lipid layer of
      presynaptic vesicle and vice versa. During the resting phase, equally charged
      lipid layers of presynaptic vesicle and cell membrane repel each other, but
      during the action potential, differently charged lipid layers strongly attract
      each other, bringing the presynaptic vesicle and cell membrane in close contact.
      Immediately thereafter, the surface tension forces open the pore and fuse both
      membranes trying to minimize the area of the contact between water fluids (extra
      and intracellular fluid) and lipid fluids (lipid membrane bilayer). Since only
      fundamental physical forces are involved in this process, it could be very fast,
      effective and almost inexhaustible. Similar mechanisms could be responsible for
      all exocytic processes and all membrane fusion processes in the cells.

PMID- 11339864
TI  - Earth--moon evolution: implications for the mechanism of the biological clock?
AB  - The geophysical characteristics of the planet Earth dictate the physiological
      traits of living organisms. Changes in the geophysical conditions over the course
      of geological time are responsible for major evolutionary changes in life
      emergence and evolvement. Calendar day length is one of earth's geophysical
      characteristics which is under a constant, if extremely small, progressive
      change. This enforces an adjustment of circadian rhythmicity throughout
      geological time. The calendar day has extended approximately 9 hours in the last
      3.5 billion years. Two mechanisms for circadian-rhythm adjustment are suggested:
      a directional selection mechanism -- an endogenous -- oriented explanation
      regarding a genetic drift in the population's endogenous oscillation toward a
      lengthened daily cycle; and an exogenous calibration mechanism - a hypothesis on
      the existence of a geophysical responsive element which senses a geophysical
      stimuli and calibrates the inner cellular oscillation in accordance with the
      length of the calendar day. A distinguishing experiment between the two
      explanations is suggested and discussed. Circadian rhythm mechanism and the
      evolution of circadian rhythmicity are tightly connected. Circadian rhythms'
      evolutionary theories are discussed in light of their contribution to our
      understanding of the selective pressures being applied throughout geological time
      and of how, once the clock has been established, it maintains an ongoing
      adjustment to a continuous change in the length of day.I argue that the exogenous
      calibration mechanism combines with the endosymbiont coordination theory,
      together, present an explanation to the path by which the calendar day adjustment
      was acquired and maintained. This hypothesis suggests a role for gravity cyclic
      force and for cytoskeleton's components in calendar day adjustment mechanism and
      circadian rhythm entrainment.

PMID- 11339865
TI  - Blindsight.
AB  - The physiological basis for blindsight -- the ability to react adequately but
      unconsciously to visual stimuli -- is assumed to be due to the transmission of
      retinal impulses from the periphery of the retina, elicited by internal
      reflections of the refracted image illuminating the interior of the eye. These
      impulses are transmitted via the superior colliculi to phylogenetic old parts of
      the brain. These same mechanisms are supposed to be responsible for phenomena
      having been confused with 'filling-in'.

PMID- 11339866
TI  - Educational facilitation: a developing role.

PMID- 11339867
TI  - A new paradigm for practice education.
AB  - This paper explores the complex nature of professional practice. It suggests that
      educating for all practice disciplines is about to undergo a paradigm shift
      whereby the value of practical education and experience will be better
      understood, more rigorously analyzed and integrated with propositional knowledge
      in the construction of personal professional knowledge and identity. It relates
      this cross disciplinary position to the present problems of skills deficits which
      are evident in nurses at the point of registration and demonstrates how
      routinization and internalization of process and tacit knowledge can create
      problems for students and newly qualified staff nurses. It also suggests how this
      can be addressed. It discusses the present culture of 'clinical education by
      default', unavailability of mentors and resources, and general lack of formal
      collaborative structures between education and service institutions and suggests
      that the present system cannot sustain the complex demands, expectations and pace
      of the clinical context and the evolution of nursing practice. Clinical
      credibility is an issue as is the current heavy clinical workload of staff nurse
      mentors, and several collaborative clinical education models are outlined which
      ensure that staff nurses or resident clinical educators are available and can
      make clinical teaching their priority. History and the present crisis in nursing
      suggest that there is a case for mandatory collaborative education/service
      structures to ensure adequate funding and to monitor the effectiveness of
      selected models so that staff nurse mentors can work with lecturer colleagues to
      articulate and teach the complexities of clinical practice through related
      research. It is predicted that this collaborative approach is capable of
      addressing both the skills deficits and the wider intellectual challenge of
      developing a new paradigm of practice education and providing an integrated base
      for continuing professional development.

PMID- 11339868
TI  - Pathways to fitness for practice: National Vocational Qualifications as a
      foundation of competence in nurse education.
AB  - Nurse education is currently undergoing major change. This article seeks to
      examine how National Vocational Qualifications (NVQs) are contributing to the
      future of nurse education. Criticisms of Project 2000 (P2K) include failure of
      the programme to produce nurses who are 'fit for practice' at the point of
      registration. A major criticism was that there is not enough skills-based
      training included. Following a recent report, recommendations were made which
      included a move to introduce a competence-based approach in nurse education. This
      approach is becoming more evident in both pre- and post-registration nurse
      education. A mapping exercise demonstrated that many of the UKCC competencies for
      pre-registration nurse education could be mapped to care NVQs. The article
      concludes that the positive aspects of care NVQs and P2K education should be
      embraced to enable programmes of nurse education to prepare nurses who are 'fit
      for practice'.

PMID- 11339869
TI  - Understanding medicines: conceptual analysis of nurses' needs for knowledge and
      understanding of pharmacology (Part I).
AB  - The advent of nurse prescribing in the United Kingdom (UK), albeit from a very
      limited formulary at first, provides a timely prompt for careful reflection on
      the extents and depths of understanding of medicines required by nurses for a
      variety of different purposes. This paper, which is the first of a two-part work,
      presents a conceptual analysis of what is required for patient care and support,
      pro re nata (as required) administration of medicines, protocol-directed
      administration of medicines (dependent prescribing), independent prescribing from
      the current Nurse Prescribers' Formulary or independent prescribing from extended
      formularies or the entire British National Formulary. It includes review, with
      common examples, of presentational issues distinguishing between approved,
      generic names of medicines and trade or brand names, and some discussion of
      combination medicines; and of recent research that has demonstrated that patient
      care was improved when the bioscience knowledge of nurses increased.

PMID- 11339870
TI  - Understanding medicines: extending pharmacology education for dependent and
      independent prescribing (Part II).
AB  - This paper relates to the extent and depth of understanding of medicines that is
      required for supply and administration of medicines under group protocol
      (dependent prescribing) (Crown 1998, 1999) for patients who are taking concurrent
      medications or independent prescribing from extended formularies or the entire
      British National Formulary. This includes a concise account of the level of
      understanding needed of: classifications, actions and effects (pharmacodynamics),
      duration of action and pharmacokinetics, interactions, and drug discovery,
      development and evaluation. A final section relates to aspects which students
      have found most challenging and provides examples of helpful explanations of
      concepts that have been found difficult. The limited familiarity of most nurses
      with chemistry is the greatest cause for anxiety, and yet it is unrealistic to
      argue the case for this subject as a prerequisite to a career in nursing.
      Instead, taking a pragmatic view of the need to meet students where they are, and
      making creative use of domestic analogies and images, has served to make
      pharmacology accessible. Examples of these aids to understanding are outlined.

PMID- 11339871
TI  - Reflecting on the use of student portfolios.
AB  - The use of portfolios in nursing has increased during recent years. We reflect
      upon the design and implementation of a portfolio for pre-registration nursing
      students in the School of Care Sciences(1)at the University of Glamorgan. The
      portfolio was introduced as the result of the need to address the theory-practice
      divide and to provide nurse students with the skills to maintain a professional
      profile upon registration. We also discuss other potential benefits associated
      with using the portfolio. These include the use of a portfolio as a focus for
      discussion between the student and their preceptor or personal tutor, a vehicle
      for the development of reflective skills and a means of assessment. We
      acknowledge that along with benefits, there are a number of potential problems
      and limitations in their use, for example, an increase in the workload for the
      student, preceptor and personal tutor. We include preliminary findings of an
      evaluation of our portfolio, revealing that both students and staff value the
      introduction of the portfolio, although currently it is not a high priority in
      terms of the course as a whole.

PMID- 11339872
TI  - Practice nursing: an evaluation of a training practice initiative.
AB  - Globally, health care is moving towards a primary care approach. In the UK
      initiatives for nurses wishing to gain experience in primary and community care
      may be crucial with the advent of Primary Care Groups (PCGs) and Primary Care
      Trusts (PCTs). This paper outlines an initiative in practice nursing, developed
      as a pilot study by a Health Authority. The training practice initiative was
      aimed at nurses returning to practice and offered them an experiential and
      supportive career pathway into primary care. The evaluation (carried out over 1
      year), highlighted that those primarily involved in the initiative--the trainees,
      educators and general practitioners--felt it had been successful, especially in
      relation to professional development issues. The funding bodies for the
      initiative, who previously had concerns over the recruitment and retention of
      practice nurses, were also optimistic that the support networks which developed
      as a result of the initiative had raised morale. The paper suggests several
      educational, organizational and professional issues which arose from the
      evaluation exercise. Further, it suggests how this initiative, in an extended
      form, could provide an effective basis for the training and development of
      nursing staff in PCGs/PCTs.

PMID- 11339873
TI  - The use of a journal club and clinical seminars on a 4-year undergraduate, pre
      registration mental- health nursing degree.
AB  - This paper presents and critically appraises the usefulness of using a journal
      club and clinical seminars as a learning strategy for mental-health nursing
      students. It begins by outlining the rationale for developing these approaches by
      discussing the importance of integrating theory with practice, and reviewing
      current developments in the education of pre-registration mental health students.
      The approach taken to organizing the sessions is then discussed. This is
      illustrated with key examples of the literature used and issues raised by the
      students. The paper concludes by highlighting the benefits of using a journal
      club and clinical seminars.

PMID- 11339874
TI  - Principles for curriculum development in Australian nursing: an examination of
      the literature.
AB  - The teaching and learning environment involves a complex interplay of various
      elements, each of which has been the subject of much educational research. This
      paper uses a framework for understanding these teaching and learning elements and
      provides a review of relevant literature. This critical review provided a
      foundation and focus for the development of a new bachelor of nursing program
      within a School of Nursing in a Queensland University.

PMID- 11339875
TI  - Principles in practice: an Australian initiative in nursing curriculum
      development.
AB  - This paper explains how curriculum values distilled from educational and nursing
      literature have been incorporated into a new bachelor of nursing program in an
      Australian University. The curriculum philosophy has been constructed to
      acknowledge the current learning climate and diverse learning styles, the active
      role teachers must play in developing competent nurses and critical thinkers, as
      well as the need to celebrate nursing's diversity whilst building a strong
      identity. The philosophy of this new curriculum is to reclaim the human dimension
      of nursing and inject renewed vigour and enthusiasm into the work of teachers and
      students.

PMID- 11339876
TI  - Focus groups as a tool for critical social research in nurse education.
AB  - Focus groups are now widely adopted in qualitative health and social research,
      and have been increasingly used as a data-collection technique in nursing
      research. The focus group is not a new method, but its uses and procedures have
      been considerably revised in recent years. The aim of this paper is to present an
      overview of the focus group as a research tool in social science literature,
      followed by a more considered discussion on the use of focus groups in
      contemporary critical social science. It draws on this work to illustrate the
      potential of focus groups to address some of the political issues in social
      research, in particular the balance of power between researcher and researched,
      and the empowerment of under-represented groups. Advantages of the method in
      connecting the researcher with group perspectives and experiences that may be
      unexplored by other methods of data collection are discussed, and the 'collective
      conscience' is put forward as an appropriate resource in data analysis. It argues
      that the application of focus-group techniques can build on experiences and
      principles of working with or participating in groups. Focus groups are
      particularly applicable to research in nurse education, for involving diverse
      stakeholders in curriculum evaluation and development, and in ongoing appraisals
      of the student's perceptions of their experience, for which universities have
      tended to rely on survey approaches and structured questionnaires. The article
      ends by drawing some conclusions from the health and social research literature
      to inform nursing education research using focus groups.

PMID- 11339880
TI  - Analysis of stress- and host cell-induced expression of the Mycobacterium
      tuberculosis inorganic pyrophosphatase.
AB  - BACKGROUND: The gene encoding the inorganic pyrophosphatase (PPase) of the
      intracellular pathogen Legionella pneumophila is induced during intracellular
      infection, but is constitutively expressed in Escherichia coli. The causative
      agent of tuberculosis, Mycobacterium tuberculosis, contains a well conserved copy
      of PPase. We sought to determine if expression of the M. tuberculosis PPase is
      regulated by the intracellular environment. RESULTS: A strain of Mycobacterium
      bovis bacille Calmette-Guerin (BCG) was constructed in which the Aequoria
      victoria green fluorescent protein (GFP) is controlled by the promoter of the M.
      tuberculosis ppa gene. After prolonged exposure of the recombinant BCG strain
      within murine bone-marrow-derived macrophages, there was no observed increased
      activity of the ppa promoter. Furthermore, there was no change in promoter
      activity after exposure to various stress stimuli such as reduced pH, osmotic
      shock, nutrient limitation or oxidative stress. CONCLUSIONS: These results
      suggest that macrophage induction of ppa is not a general phenomenon among
      intracellular pathogens.

PMID- 11339882
TI  - The analysis of circumsporozoite-protein gene sequences from South Korean
      isolates of Plasmodium vivax.
AB  - The amino-acid sequences corresponding to the circumsporozoite protein (CSP) of
      Plasmodium vivax fall into two main types, VK210 and VK247, each of which has a
      characteristic tandem repeat. When the repetitive domains of the CSP gene from
      six isolates of P. vivax from South Korea were sequenced they were found to show
      a total of 20 tandem amino-acid repeats, and repeat patterns that are regular and
      distinct from those of other P. vivax isolates. The amino-acid sequences of the
      South Korean parasites were found to be most similar to those of three isolates
      from China (CH-3, CH-4, and CH-5) and, particularly, to one from North Korea. A
      sequence (AGGNAANKKAEDAGGNA) and two repeats of the sequence GGNA found in the
      North Korean parasites were found in all six isolates from South Korea. The South
      Korean parasites investigated appear phylogenetically identical and unique to the
      Korean peninsula.

PMID- 11339881
TI  - The concentration of three anti-seizure medications in hair: the effects of hair
      color, controlling for dose and age.
AB  - BACKGROUND: This paper assess the relationship between the quantity of three anti
      seizure medications in hair and the color of the analyzed hair, while controlling
      for the effects of dose, dose duration, and patient age for 140 clinical patients
      undergoing anti-seizure therapy. Three drugs are assessed: carbamazepine (40
      patients), valproic acid (40 patients), and phenytoin (60 patients). The
      relationship between hair assay results, hair color, dose, dose duration, and age
      is modeled using an analysis of covariance. The covariance model posits the hair
      assay results as the dependent variable, the hair color as the qualitative
      categorical independent variable, and dose, dose duration, and age as covariates.
      The null hypothesis assessed is that there is a no relationship between hair
      color and the quantity of analyte determined by hair assay such that darker
      colored hair will demonstrate higher concentrations of analyte than lighter
      colored hair. RESULTS: The analysis reveals that there is a significant
      relationship between dose and concentration for all hair color categories
      independent of the other covariates or the categorical independent variable.
      CONCLUSION: There does not appear to be any relationship between carbamazepine
      concentration and hair color. There is a weak relationship between hair color and
      valproic acid concentration, which the data suggest may be mediated by age. There
      is a significant, moderate relationship between phenytoin concentration and hair
      color such that darker colored hair has greater concentration values than lighter
      colored hair.

PMID- 11339883
TI  - Madagascan isolates of Plasmodium falciparum showing low sensitivity to
      artemether in vitro.
AB  - In Madagascar, although chloroquine (CQ) remains the first-line treatment of
      choice for malaria, the gradual spread of resistance to this antimalarial drug is
      of increasing concern. As part of a larger investigation of the effectiveness of
      the second- and third-line drugs used to treat malaria, the in-vitro
      susceptibilities of Plasmodium falciparum collected in Madagascar to CQ,
      mefloquine (MQ) and artemether (ART) were therefore investigated. Median
      inhibitory concentrations (IC(50)) were determined for isolates collected from
      residents of two villages in the foothills of the central highlands. The IC(50)
      for ART ranged from 0.23-17.50 nM [N = 51; geometric mean = 4.02 nM; 95%
      confidence interval (CI) = 2.99-5.05 nM], four isolates exhibiting IC(50) (> 12
      nM) indicative of resistance to this drug. The artemether IC(50) were found to be
      correlated with those of CQ (N = 46; Spearman's r = 0.51; P = 0.0002), which
      varied widely (0.4-254.3 nM; mean = 23.4 nM; CI = 7.1-39.7 nM; N = 46). Five
      (11%) of the 46 isolates exposed to CQ in vitro were considered resistant to this
      drug (i.e. to have IC(50) > 100 nM), with IC(50) ranging from 109-245.3 nM (mean
      = 171.6 nM; CI = 110.4-232.8 nM). However, all the CQ-resistant isolates were
      considered sensitive to ART and vice versa. All the isolates tested also appeared
      sensitive to MQ (IC(50) = 2.21-43.1 nM; mean = 10.5 nM; CI = 7.95-13.07 nM; N =
      46), the IC(50) for MQ being correlated with those for CQ (N = 46; Spearman's r
      =0.46; P = 0.001). There was no significant correlation between ART and MQ
      activities. Although the sample was fairly small, the present results indicate
      that P. falciparum in Madagascar is generally becoming less sensitive to CQ and
      ART. The observation of a correlation between the IC(50) for these two drugs
      perhaps indicates that artemisinin derivatives would be better used in
      combination with antimalarial drugs other than 4-aminoquinolines.

PMID- 11339884
TI  - American cutaneous leishmaniasis in Guyana, South America.
AB  - The 185 patients who presented at the dermatology clinic of Georgetown Public
      Hospital, Guyana, between 1992 and 1998, with skin ulcers indicative of American
      cutaneous leishmaniasis (ACL) were retrospectively reviewed. The laboratory
      confirmed cases of ACL were identified and the corresponding data were analysed
      for risk factors such as age, gender, areas of residence and of possible exposure
      to the causative agent (Leishmania braziliensis guyanensis), ethnic origin,
      longevity of the ulcers, and treatment regimes prior to the definitive diagnosis.
      Eighty-one (43%) of the 185 subjects were confirmed to be infected with Le. b.
      guyanensis. Although 53 (66%) of the cases lived in or close to the capital city,
      Georgetown, most of the cases had travelled to (and probably been infected in)
      region X in the interior of Guyana (32%) or regions VII (23%), VIII (23%), IX
      (11%), VI (5%), I (3%) or III (3%), usually because they were involved in the
      mining (41%) or lumber (21%) industries, the army or hunting. Almost all (95%) of
      the cases were male and most (58%) were aged 20-39 years. In general, the cases
      had had their skin lesions for many days before presenting for treatment: 46% for
      1-5 weeks and 3% for > 6 months. Prior to presentation at the clinic, many of the
      cases had attempted to cure themselves, using local herbal remedies (37%),
      antibiotics and antifungal remedies (39%), other creams (5%), household chemicals
      (9%) or miscellaneous remedies such as lead salts (especially lead sulphate) and
      battery acid, all without success. Recommendations are made for an
      epidemiological study of active ACL among forest workers, eco-tourists and
      residents of high-risk areas. Diagnostic centres need to be sited in the regions
      most at-risk, particularly in or near environments in which the main vectors -
      sandflies such as Lutzomyia umbratilis, Lu. anduzei and Lu. whitmani - are known
      to be prevalent.

PMID- 11339885
TI  - Wuchereria bancrofti in a community with seasonal transmission: stability of
      microfilaraemia, antigenaemia and filarial-specific antibody concentrations.
AB  - The effect of seasonal transmission on microfilaraemia, antigenaemia and filarial
      specific antibody levels in individuals infected with Wuchereria bancrofti was
      investigated in a follow-up study in an endemic community in north-eastern
      Tanzania. The subjects were 37 adult male residents who were found to be positive
      for circulating filarial antigen (CFA) at the beginning of the study (26 of whom
      were also found microfilaraemic with W. bancrofti at this time). Blood samples
      were collected from each subject in July 1998, January 1999 and July 1999, during
      the seasons when transmission intensity was high, low and high, respectively. The
      mean intensities of microfilaraemia and the mean concentrations of CFA were each
      slightly higher during the low-transmission season than during the two high
      transmission seasons but the differences were not statistically significant (P >
      0.05). Similarly, the mean levels of filarial-specific IgG1, IgG2, IgG3, IgG4 or
      IgE did not differ to a statistically significant degree between the three
      examination times. Microfilaraemias and the levels of CFA and filarial-specific
      antibodies all therefore appeared to be remarkably stable and largely unaffected
      by the seasonal variation in transmission. That no variation in the mean IgG4/IgE
      ratio was observed over the study period may indicate that the level of
      resistance to W. bancrofti infection in the study subjects was also unaffected by
      the transmission season.

PMID- 11339886
TI  - Epidemiology of bancroftian filariasis in three suburban areas of Matara, Sri
      Lanka.
AB  - The epidemiological parameters of bancroftian filariasis were investigated in
      three suburbs of Matara, within the south-western coastal belt of Sri Lanka where
      the disease is endemic. The overall prevalence of microfilaraemia and the
      geometric mean density of the microfilaraemias observed were 4.4% and 20.6
      microfilariae/60 microl fingerprick blood, respectively. Prevalence was
      significantly lower in the female subjects than in the male, and in males aged <
      20 years than in older males. Overall, 9.5% of the subjects had the clinical
      manifestations of bancroftian filariasis (6.4% had filarial fever, 3.0% had
      elephantiasis and/or oedema, and 6.2% had hydrocele). The prevalence of
      elephantiasis/oedema was generally higher among the female subjects (4.2%) than
      among the male (1.4%), and an age-prevalence plot for this manifestation showed a
      linear increase in prevalence after the age of 40 years. Hydrocele also became
      commoner with increasing age, but this increase in prevalence began at the lower
      age of 20 years. More than 60% of the cases of elephantiasis/oedema but only
      26.3% of the subjects found to have hydroceles experienced filarial fever
      attacks. The cases of fever and elephantiasis/oedema (but not those of
      microfilaraemia or hydrocele) were aggregated within households. However, the
      children whose mothers were microfilaraemic were much more likely to be
      microfilaraemic themselves (8.7%) than the children who had amicrofilaraemic
      mothers (2.8%), microfilaraemic fathers (0.0%) or amicrofilaraemic fathers
      (2.7%). The results of entomological surveys indicated that transmission of
      Wuchereria bancrofti occurred throughout the year in the study community.

PMID- 11339887
TI  - Community-directed health (CDH) workers enhance the performance and
      sustainability of CDH programmes: experience from ivermectin distribution in
      Uganda.
AB  - The performance and 'drop-out' rates of ivermectin (Mectizan) distributors in the
      Ugandan programme for community-directed treatment with ivermectin (CDTI) were
      investigated and related to the manner in which the distributors were recruited.
      Distributors, from randomly selected communities endemic for onchocerciasis in
      seven of the 10 affected districts, were interviewed. Questionnaires were
      initially completed for 296 communities (in which ivermectin had been distributed
      in 1998 but not in 1999) and then extended to another 310 communities (in which
      ivermectin had been distributed in both study years). Discussions were also held
      with some other community members, in participatory evaluation meetings (PEM) in
      14 communities from four districts. Despite the CDTI being labelled as 'community
      directed', the first round of interviews and questionnaires revealed that there
      were in fact three categories of distributors: 322 (69.4%) of those questioned
      had been selected by community members and were therefore truly community
      directed health workers (CDHW) but 101 (22%) were community-based health workers
      appointed by the leaders of the local council (CBHW-LC) and 41 (9%) were self
      appointed volunteers (CBHW-SA). During 1999, only the CDHW received good
      community support; they still helped to mobilise and educate their community
      members and advocate CDTI, and 98% of them agreed that they would distribute
      ivermectin during the following year. In contrast, many of the CBHW-LC were
      neither supported nor appreciated by the community members. Presumably in
      consequence, many of the CBHW-LC did not help to mobilise or educate their
      community members in 1999, nor did they advocate CDTI. Almost all (95%) of the
      CBHW-LC said that they would not be available to distribute in the following
      year, and were therefore regarded as total 'drop-outs' from the CDTI. The CBHW-SA
      were better supported by community members than were the CBHW-LC, they did more
      to advocate the CDTI, and 93% reported that they would distribute ivermectin
      during the following year. The 'drop-out' rates for 1999 were < 2% for the CDHW,
      7% for the CBHW-SA, and 95% for the CBHW-LC. The results also indicated that the
      CBHW-SA were not as reliable as the CDHW. Similar results were obtained from the
      second round of questionnaires, in which 224 (73%) of the interviewees were CDHW,
      57 (18%) were CBHW-LC and 28 (9%) were CBHW-SA. The results of the PEM showed
      that the CDHW, who mainly came from the same kinship groups as the people who
      selected them, were likely to achieve higher ivermectin coverage within a week
      than the other categories of distributors. It is clear that, for the optimum
      performance and sustainability of the CDTI, the distributors used should be CDHW
      selected by their own community members.

PMID- 11339888
TI  - Similarity of the patterns of sensilla on the antennae of Triatoma melanosoma and
      Triatoma infestans.
AB  - The patterns of sensilla on the antennae of sylvatic Triatoma melanosoma Lent,
      Jurberg, Galvao and Carcavallo 1994 were compared with those of three samples of
      Triatoma infestans (Klug 1834) - one of domestic populations in Paraguay,
      Bolivia, Argentina and Chile, one of the sylvatic 'dark morph' from the Bolivian
      Chaco, and one from sylvatic sites in the Cochabamba region of Bolivia. The
      results of multivariate analysis indicated that, in terms of their antennal
      sensilla, the T. melanosoma and the 'dark morph' of T. infestans were more
      similar to the domestic T. infestans than to the sylvatic T. infestans from
      Cochabamba. As in previous molecular and genetic studies, there was no evidence
      to indicate that the bugs identified as T. melanosoma and those identified as T.
      infestans belonged to different species. The taxonomic position of T. melanosoma
      should therefore be reconsidered.

PMID- 11339889
TI  - Phlebotomine sandflies in Venezuela. V. Review of the genus Brumptomyia (Diptera:
      Psychodidae), with description of the female of Brumptomyia devenanzii, re
      description of the male and isozymatic profile.
AB  - Recently collected data on the Venezuelan species of the genus Brumptomyia are
      used to produce an updated review of these sandflies. At present, four species
      are recognized in Venezuela: B. devenanzii, B. beaupertuyi, B. avellari and B.
      pintoi. A key for the males is given and the geographical distribution of each of
      these species is outlined. The previously unknown female of B. devenanzii is
      described, the male is re-described, and the genetic variability (based on 11
      enzymatic loci) of this species and of B. beaupertuyi (a sympatric species in
      Rancho Grande, the type locality of B. devenanzii) are reported. Fixed allelic
      differences in one diagnostic locus (adenylate kinase; Ak), between sympatric and
      allopatric populations, allowed for the unequivocal separation of both sexes of
      B. beaupertuyi from those of B. devenanzii. Significant inter-specific
      differences were also detected in the allele frequencies of malate dehydrogenase
      (Mdh-2) and decarboxylating malate dehydrogenase (Me). For B. devenanzii, mean
      heterozygosity and mean number of alleles per locus ranged from 2.0%-3.1% and 1.1
      1.5, respectively. The corresponding values for B. beaupertuyi were 3.8% and 1.2.

PMID- 11339890
TI  - Use of the DELI-microtest to determine the drug sensitivity of Plasmodium
      falciparum in Burkina Faso.

PMID- 11339891
TI  - Detection and direct genomic sequencing of multiple rare unknown flanking DNA in
      highly complex samples.
AB  - By identifying the sequence of retro- and lentiviral integration sites in
      peripheral blood leukocytes, the clonal composition and fate of genetically
      modified hematopoietic progenitor and stem cells could be mapped in vitro and in
      vivo. Previously available methods have been limited to the analysis of mono- or
      oligoclonal integration sites present in high copy numbers. Here, we perform
      characterization of multiple rare retroviral and lentiviral integration sites in
      highly complex DNA samples. The reliability of this method results from nontarget
      DNA removal via magnetic extension primer tag selection (EPTS) preceding solid
      phase ligation-mediated PCR. EPTS/LM-PCR allowed the simultaneous direct genomic
      sequencing of multiple proviral LTR-flanking sequences of retro- and lentiviral
      vectors even if only 1 per 100 to 1000 cells contained the provirus. A primer
      walking "around" the integration locus demonstrated the adaptability of EPTS/LM
      PCR to study unknown flanking DNA regions unrelated to proviruses. The technique
      is fast, inexpensive, and sensitive in minimal samples. It enables studies of
      retro- and lentiviral integration, viral vector tracking in gene therapy,
      insertional mutagenesis, transgene integration, and direct genomic sequencing
      that until now have been difficult or impossible to perform.

PMID- 11339892
TI  - A clinical inflammatory syndrome attributable to aerosolized lipid-DNA
      administration in cystic fibrosis.
AB  - Immunologic reactivity to lipid-DNA conjugates has traditionally been viewed as
      less of an issue than with viral vectors. We performed a dose escalation safety
      trial of aerosolized cystic fibrosis transmembrane conductance regulator (CFTR)
      cDNA to the lower airways of eight adult cystic fibrosis patients, and monitored
      expression by RT-PCR. The cDNA was complexed to a cationic lipid amphiphile (GL
      67) consisting of a cholesterol anchor linked to a spermine head group. CFTR
      transgene was detected in three patients at 2-7 days after gene administration.
      Four of the eight patients developed a pronounced clinical syndrome of fever
      (maximum of 103.3EF), myalgias, and arthralgia beginning within 6 hr of gene
      administration. Serum IL-6 but not levels of IL-8, IL-1, TNF-alpha, or IFN-gamma
      became elevated within 1-3 hr of gene administration. No antibodies to the
      cationic liposome or plasmid DNA were detected. We found that plasmid DNA by
      itself elicited minimal proliferation of peripheral blood mononuclear cells taken
      from study patients, but led to brisk immune cell proliferation when complexed to
      a cationic lipid. Lipid and DNA were synergistic in causing this response.
      Cellular proliferation was also seen with eukaryotic DNA, suggesting that at
      least part of the immunologic response to lipid-DNA conjugates is independent of
      unmethylated (E. coli-derived) CpG sequences that have previously been associated
      with innate inflammatory changes in the lung.

PMID- 11339893
TI  - Tumor suppression and therapy sensitization of localized and metastatic breast
      cancer by adenovirus p53.
AB  - We have examined the effects of a replication-defective adenovirus encoding p53
      (RPR/INGN 201 [Ad5CMV-p53]; Adp53), alone or in combination with the breast
      cancer therapeutic doxorubicin (Adriamycin), to suppress growth and induce
      apoptosis in breast cancer cells in vitro. We have also examined the in vivo
      effect of intratumoral administration of Adp53, alone or in combination with
      doxorubicin, to suppress the growth of established subcutaneous MDA-MB-435 breast
      cancer tumors. Finally, using the MDA-MB-435 orthotopic model of metastatic
      breast cancer, we have examined the effect of systemic administration of Adp53,
      alone or in combination with doxorubicin, to reduce the incidence of metastases.
      We find that whereas in vitro treatment of cells with Adp53 reduces
      [(3)H]thymidine incorporation by about 90% at 48 hr, cell viability at 6 days is
      reduced by only some 50% relative to controls. Although apoptosis is detectable
      in Adp53-treated cultures, these results suggest that a large fraction of Adp53
      treated cells merely undergo reversible cell cycle arrest. Combined treatment
      with Adp53 and doxorubicin results in a greater than additive loss of viability
      in vitro and increased apoptosis. In vivo, locally administered Adp53 suppresses
      growth of established subcutaneous tumors in nude mice and suppression is
      enhanced by doxorubicin. In the metastatic breast cancer model, systemic
      administration of Adp53 plus doxorubicin leads to a significant reduction in the
      incidence of metastases relative to Adp53 or doxorubicin alone. Taken together,
      these data indicate an additive to synergistic effect of Adp53 and doxorubicin
      for the treatment of primary and metastatic breast cancer.

PMID- 11339894
TI  - Cochlear function and transgene expression in the guinea pig cochlea, using
      adenovirus- and adeno-associated virus-directed gene transfer.
AB  - Development of a viral vector that can infect hair cells of the cochlea without
      producing viral-associated ototoxic effects is crucial for utilizing gene
      replacement therapy as a treatment for certain forms of hereditary deafness. In
      the present study, cochlear function was monitored using distortion-product
      otoacoustic emissions (DPOAEs) in guinea pigs that received infusions of either
      (E1(-), E3(-)) adenovirus, or adeno-associated virus (AAV), directly into the
      scala tympani. Replication-deficient (E1(-), E3(-)) adenovirus-directed gene
      transfer, using the cytomegalovirus (CMV) promoter, drove transgene expression to
      inner hair cells and pillar cells of the cochlea. AAV transduction was tested
      with several promoters, such as platelet-derived growth factor (PDGF), neuron
      specific enolase (NSE), and elongation factor 1alpha (EF-1alpha) promoters; which
      drove transgene expression to cochlear blood vessels, nerve fibers, and certain
      spiral limbus cells, respectively. AAV transgene expression was visualized by
      green fluorescent protein immunostaining. Immunocytochemistry to heparan sulfate
      confirmed the absence of proteoglycans in guinea pig hair cells, indicating that
      the receptor for AAV was not present on these cells. However, the heparan sulfate
      proteoglycan expression pattern mimicked the AAV transduction pattern. An overall
      finding was that cochlear function was not altered throughout the infection
      period using AAV titers as high as 5 x 10(8) IP/infused cochlea. In contrast,
      cochlear function was severely compromised by 8 days postinfection with
      adenoviral titers of 5 x 10(8) PFU/infused cochlea, and outer hair cells were
      eliminated. Thus, cochlear hair cells are amenable to in vivo gene transfer using
      a replication-deficient (E1(-), E3(-)) adenovirus. However, replication-defective
      or gutted adenovirus vectors must be employed to overcome the ototoxic effects of
      (E1(-), E3(-)) adenovirus vectors.

PMID- 11339895
TI  - Matrix immobilization enhances the tissue repair activity of growth factor gene
      therapy vectors.
AB  - Although growth factor proteins display potent tissue repair activities,
      difficulty in sustaining localized therapeutic concentrations limits their
      therapeutic activity. We reasoned that enhanced histogenesis might be achieved by
      combining growth factor genes with biocompatible matrices capable of immobilizing
      vectors at delivery sites. When delivered to subcutaneously implanted sponges, a
      platelet-derived growth factor B-encoding adenovirus (AdPDGF-B) formulated in a
      collagen matrix enhanced granulation tissue deposition 3- to 4-fold (p < or =
      0.0002), whereas vectors encoding fibroblast growth factor 2 or vascular
      endothelial growth factor promoted primarily angiogenic responses. By day 8
      posttreatment of ischemic excisional wounds, collagen-formulated AdPDGF-B
      enhanced granulation tissue and epithelial areas up to 13- and 6-fold (p <
      0.009), respectively, and wound closure up to 2-fold (p < 0.05). At longer times,
      complete healing without excessive scar formation was achieved. Collagen matrices
      were shown to retain both vector and transgene products within delivery sites,
      enabling the transduction and stimulation of infiltrating repair cells.
      Quantitative PCR and RT-PCR demonstrated both vector DNA and transgene mRNA
      within wound beds as late as 28 days posttreatment. By contrast, aqueous
      formulations allowed vector seepage from application sites, leading to PDGF
      induced hyperplasia in surrounding tissues but not wound beds. Finally, repeated
      applications of PDGF-BB protein were required for neotissue induction approaching
      equivalence to a single application of collagen-immobilized AdPDGF-B, confirming
      the utility of this gene transfer approach. Overall, these studies demonstrate
      that immobilizing matrices enable the controlled delivery and activity of tissue
      promoting genes for the effective regeneration of injured tissues.

PMID- 11339896
TI  - Cationic liposome-mediated gene delivery to the liver and to hepatocellular
      carcinomas in mice.
AB  - The potential of cationic liposomes as nonviral vectors for in vivo gene delivery
      to the liver and to intrahepatic hepatocellular carcinoma (HCC) was investigated.
      Mice were injected via the tail vein or portal vein with a cationic lipid
      complexed to plasmid DNA (pDNA) encoding the chloramphenicol acetyltransferase
      (CAT) reporter gene at various cationic lipid:pDNA molar ratios to analyze the
      efficiency of gene delivery after intravenous administration. Tail vein injection
      resulted in high CAT expression levels in lung and spleen and low levels in the
      liver. Portal vein injection, by comparison, significantly enhanced hepatic
      reporter gene expression but also resulted in pronounced hepatic toxicity. Gene
      delivery to intrahepatic tumors produced by intrahepatic injection of human HCC
      cells was analyzed in nude mice. Tail vein injection as well as portal vein
      injection resulted in low levels of gene expression in intrahepatic tumors. By
      comparison, high levels of gene expression were achieved by direct, intratumoral
      injection of liposome-pDNA complexes, with only minimal expression in the
      surrounding normal liver. Therefore, direct liposome-pDNA complex injection
      appears far superior to systemic or portal intravenous administration for gene
      therapy of localized intrahepatic tumors, and may be a useful adjunct in the
      treatment of human HCCs.

PMID- 11339897
TI  - Use of viral fusogenic membrane glycoproteins as novel therapeutic transgenes in
      gliomas.
AB  - Malignant gliomas are the most common primary brain tumors in adults and, with
      few exceptions, have a dismal prognosis despite the therapeutic use of surgery,
      radiation therapy, and chemotherapy. Because CNS gliomas rarely metastasize, they
      represent an attractive target for gene therapy through local gene delivery. Here
      we report on the use of two different fusogenic membrane glycoproteins (FMGs),
      the measles virus proteins F and H (MV-F and MV-H) and a mutated form of the
      retroviral envelope protein of the gibbon ape leukemia virus (GALV.fus), as a
      novel class of therapeutic transgenes in gliomas. Transfection of U87 and U118
      cells with MV-F and MV-H cDNA or GALV.fus cDNA led in 48 hr to massive syncytial
      formation followed by cell death. FMG-mediated cytotoxicity in the U87 and U118
      cell lines was superior to the cytotoxicity caused by transfection with HSV-tk
      cDNA followed by ganciclovir (GCV) treatment at all time points. At high-density
      cell seeding, addition of tumor cells transfected with MV-F and H killed at least
      1 log more cells than by HSV-tk + GCV treatment, indicating higher bystander
      effect. Similar results were obtained with GALV.fus. The mechanism of syncytial
      death in cultured glioma cell lines was predominantly apoptotic. Transfection of
      U87 cells with F + H or GALV.fus expression constructs completely suppressed
      their tumorigenicity. Treatment of established U87 xenografts in nude mice with a
      combination of F and H adenoviruses at 1:1 ratio led to complete tumor
      regression, significantly higher antitumor effect, and prolongation of survival
      as compared with control animals treated with a GFP adenovirus. In summary, the
      viral fusogenic membrane glycoproteins (GALV and the MV-F + MV-H combination) are
      potent therapeutic transgenes with potential utility in the gene therapy of
      gliomas.

PMID- 11339898
TI  - A new immunodeficient mouse model for human myoblast transplantation.
AB  - Design of efficient transplantation strategies for myoblast-based gene therapies
      in humans requires animal models in which xenografts are tolerated for long
      periods of time. In addition, such recipients should be able to withstand
      pretransplantation manipulations for enhancement of graft growth. Here we report
      that a newly developed immunodeficient mouse carrying two known mutations (the
      recombinase activating gene 2, RAG2, and the common cytokine receptor gamma,
      gammac) is a candidate fulfilling these requirements. Skeletal muscles from RAG2(
      /-)/gammac(-/-) double mutant mice recover normally after myotoxin application or
      cryolesion, procedures commonly used to induce regeneration and improve
      transplantation efficiency. Well-differentiated donor-derived muscle tissue could
      be detected up to 9 weeks after transplantation of human myoblasts into RAG2(-/
      )/gammac(-/-) muscles. These results suggest that the RAG2(-/-)/gammac(-/-) mouse
      model will provide new opportunities for human muscle research.

PMID- 11339899
TI  - Immune consequences of intraocular administration of modified adenoviral vectors.
AB  - To investigate the immune consequences of intraocular administration of modified
      adenoviral vectors, C57BL/6 normal and retinal degeneration C57BL/6 (rd/rd) mice
      were immunized with subcutaneous, subretinal, vitreal, or anterior chamber
      injections of replication-deficient adenovirus (AdV) containing the Escherichia
      coli beta-galactosidase gene (AdV-LacZ). Fourteen days after the initial
      inoculation, the animals were immune challenged with an injection of AdV-LacZ in
      the right ear pinna. Antigen-induced delayed type hypersensitivity (DTH) was
      measured by determining relative ear swelling. Normal C57BL/6 mice immunized with
      subretinal, vitreal, or anterior chamber injections did not demonstrate a DTH
      response. The rd/rd C57BL/6 mice injected in the anterior chamber with the viral
      construct also did not respond with DTH in a manner similar to normal mice
      responding to intraocular injection and subsequent challenge. However, the rd/rd
      C57BL/6 mice immunized by the subretinal or vitreal route did respond to immune
      challenge with a DTH response. Histologic examination of the eyes showed a lack
      of infiltration by inflammatory cells. Although these results suggest that the
      potential for immune consequences is reduced when modified adenoviral vectors are
      used in the normal ocular environment, these vectors used in the vitreal cavity
      of rd/rd animals may induce a systemic response to the vectors.

PMID- 11339900
TI  - Preexisting antiadenoviral immunity is not a barrier to efficient and stable
      transduction of the brain, mediated by novel high-capacity adenovirus vectors.
AB  - The utility of first-generation adenovirus vectors for long-term gene transfer in
      humans is limited by preexisting antiadenoviral immunity. We demonstrate here
      that new-generation high-capacity adenovirus vectors (HC-Ads) can efficiently
      transduce the brain and mediate stable transgene expression for at least 2
      months, even in the presence of a preexisting antiadenoviral immune response.
      First-generation vector-mediated transduction was almost completely abolished in
      preimmunized animals within 60 days of the vector injection. Levels of HC-Ad
      mediated transduction by 3 days postinjection were not significantly affected by
      preimmunization, were reduced within 14 days to 56% of those levels seen in
      nonimmunized animals, and remained stable until day 60 postinjection. Acute brain
      inflammation elicited by the HC-Ad vector injection was more transient, and was
      reduced in intensity compared with brain inflammation elicited by the first
      generation vector injection in immunized animals. Inflammation was significantly
      higher in all immunized animals than in nonimmunized animals. Our results show
      that preexisting antiadenoviral immunity does not significantly reduce initial HC
      Ad-mediated infection of the brain and is not a barrier to stable HC-Ad vector
      mediated transduction of the CNS. Although input HC-Ad capsid proteins injected
      into the brain may contain transient targets for a brain-infiltrating cellular
      adenovirus-specific immune response, this fails to eliminate transgene
      expression. Thus HC-Ads show promise for gene therapy of chronic brain disease.

PMID- 11339901
TI  - Development of an Rev-independent, minimal simian immunodeficiency virus-derived
      vector system.
AB  - Lentiviral vectors are attractive candidates for gene therapy because of their
      ability to integrate into nondividing cells. To date, conventional HIV-1-based
      vectors can be produced at higher titers, but concerns regarding their safety for
      human use exist because of the possibility of recombination leading to production
      of infectious virions with pathogenic potential. Development of lentivirus
      vectors based on nonhuman lentiviruses constitutes an active area of research. We
      described a novel HIV-SIV hybrid vector system in which an HIV-1-derived transfer
      vector is encapsidated by SIVmac1A11 core particles and pseudotyped with VSV
      glycoprotein G. In an effort to further develop this vector system, we modified
      the packaging plasmid by deletion of the SIV accessory genes. Specifically,
      versions of the packaging plasmid (SIVpack) lacking vif, vpr, vpx, and/or nef
      were constructed. Our results indicate that, as with HIV-1-based packaging
      plasmids, deletion of accessory genes has no significant effect on transduction
      in either dividing or nondividing cells. The SIV packaging plasmid was also
      modified with regard to the requirement for RRE and rev. Deletion of the RRE and
      rev from SIVpack led to dramatic loss of transduction ability. Introduction of
      the 5' LTR from the spleen necrosis virus to packaging plasmids lacking RRE/Rev
      was then sufficient to fully restore vector titer. A minimal SIV transfer vector
      was also developed, which does not require RRE/Rev and exhibits no reduction in
      transduction efficiency in two packaging systems. The SIV-based vector system
      described here recapitulates the biological properties of minimal HIV-1-derived
      systems and is expected to provide an added level of safety for human gene
      transfer. We suggest that the SIV-derived vector system will also be useful to
      deliver anti-HIV-1 gene therapy reagents that would inhibit an HIV-1-derived
      vector.

PMID- 11339903
TI  - An algorithm for approximate tandem repeats.
AB  - A perfect single tandem repeat is defined as a nonempty string that can be
      divided into two identical substrings, e.g., abcabc. An approximate single tandem
      repeat is one in which the substrings are similar, but not identical, e.g.,
      abcdaacd. In this paper we consider two criterions of similarity: the Hamming
      distance (k mismatches) and the edit distance (k differences). For a string S of
      length n and an integer k our algorithm reports all locally optimal approximate
      repeats, r = umacro u, for which the Hamming distance of umacro and u is at most
      k, in O(nk log (n/k)) time, or all those for which the edit distance of umacro
      and u is at most k, in O(nk log k log (n/k)) time. This paper concentrates on a
      more general type of repeat called multiple tandem repeats. A multiple tandem
      repeat in a sequence S is a (periodic) substring r of S of the form r = u(a)u',
      where u is a prefix of r and u' is a prefix of u. An approximate multiple tandem
      repeat is a multiple repeat with errors; the repeated subsequences are similar
      but not identical. We precisely define approximate multiple repeats, and present
      an algorithm that finds all repeats that concur with our definition. The time
      complexity of the algorithm, when searching for repeats with up to k errors in a
      string S of length n, is O(nka log (n/k)) where a is the maximum number of
      periods in any reported repeat. We present some experimental results concerning
      the performance and sensitivity of our algorithm. The problem of finding repeats
      within a string is a computational problem with important applications in the
      field of molecular biology. Both exact and inexact repeats occur frequently in
      the genome, and certain repeats occurring in the genome are known to be related
      to diseases in the human.

PMID- 11339904
TI  - Reducing mass degeneracy in SAR by MS by stable isotopic labeling.
AB  - Mass spectrometry (MS) promises to be an invaluable tool for functional genomics,
      by supporting low-cost, high-throughput experiments. However, large-scale MS
      faces the potential problem of mass degeneracy---indistinguishable masses for
      multiple biopolymer fragments (e.g., from a limited proteolytic digest). This
      paper studies the tasks of planning and interpreting MS experiments that use
      selective isotopic labeling, thereby substantially reducing potential mass
      degeneracy. Our algorithms support an experimental--computational protocol called
      structure-activity relation by mass spectrometry (SAR by MS) for elucidating the
      function of protein-DNA and protein-protein complexes. SAR by MS enzymatically
      cleaves a crosslinked complex and analyzes the resulting mass spectrum for mass
      peaks of hypothesized fragments. Depending on binding mode, some cleavage sites
      will be shielded; the absence of anticipated peaks implicates corresponding
      fragments as either part of the interaction region or inaccessible due to
      conformational change upon binding. Thus, different mass spectra provide evidence
      for different structure--activity relations. We address combinatorial and
      algorithmic questions in the areas of data analysis (constraining binding mode
      based on mass signature) and experiment planning (determining an isotopic
      labeling strategy to reduce mass degeneracy and aid data analysis). We explore
      the computational complexity of these problems, obtaining upper and lower bounds.
      We report experimental results from implementations of our algorithms.

PMID- 11339905
TI  - On differential variability of expression ratios: improving statistical inference
      about gene expression changes from microarray data.
AB  - We consider the problem of inferring fold changes in gene expression from cDNA
      microarray data. Standard procedures focus on the ratio of measured fluorescent
      intensities at each spot on the microarray, but to do so is to ignore the fact
      that the variation of such ratios is not constant. Estimates of gene expression
      changes are derived within a simple hierarchical model that accounts for
      measurement error and fluctuations in absolute gene expression levels.
      Significant gene expression changes are identified by deriving the posterior odds
      of change within a similar model. The methods are tested via simulation and are
      applied to a panel of Escherichia coli microarrays.

PMID- 11339906
TI  - On the structure of syntenic distance.
AB  - This paper examines some of the rich structure of the syntenic distance model of
      evolutionary distance, introduced by Ferretti et al. (1996). The syntenic
      distance between two genomes is the minimum number of fissions, fusions, and
      translocations required to transform one into the other, ignoring gene order
      within chromosomes. We prove that the previously unanalyzed algorithm given by
      Ferretti et al. (1996) is a 2-approximation and no better, and that, further, it
      always outperforms the algorithm presented by DasGupta et al. (1998). We also
      prove the same results for an improved version of the Ferretti et al. algorithm.
      We then prove a number of properties which give insight into the structure of
      optimal move sequences. We give instances in which any move sequence working
      solely within connected components is nearly twice optimal and prove a general
      lower bound based on the spread of genes from each chromosome. We then prove a
      monotonicity property for the syntenic distance, and bound the difficulty of the
      hardest instance of any size. We discuss the results of implementing these
      algorithms and testing them on real and simulated synteny data.

PMID- 11339907
TI  - Perfect phylogenetic networks with recombination.
AB  - The perfect phylogeny problem is a classical problem in evolutionary tree
      construction. In this paper, we propose a new model called phylogenetic network
      with recombination that takes recombination events into account. We show that the
      problem of finding a perfect phylogenetic network with the minimum number of
      recombination events is NP-hard; we also present an efficient polynomial time
      algorithm for an interesting restricted version of the problem.

PMID- 11339908
TI  - Hitch-hiking: a parallel heuristic search strategy, applied to the phylogeny
      problem.
AB  - The article introduces a parallel heuristic search strategy ("Hitch-hiking")
      which can be used in conjunction with other random-walk heuristic search
      strategies. It is applied to an artificial phylogeny problem, in which character
      sequences are evolved using pseudo-random numbers from a hypothetical ancestral
      sequence. The objective function to be minimized is the minimum number of
      character-state changes required on a binary tree that could account for the
      sequences observed at the tips (leaves) of the tree -- the Maximum Parsimony
      criterion. The Hitch-hiking strategy is shown to be useful in that it is robust
      and that on average the solutions found using the strategy are better than those
      found without. Also the strategy can dynamically provide information on the
      characteristics of the landscape of the problem. I argue that Hitch-hiking as a
      scheme for parallelization of existing heuristic search strategies is of
      potentially very general use, in many areas of combinatorial optimization.

PMID- 11339909
TI  - Vaginal clindamycin in preventing preterm birth and peripartal infections in
      asymptomatic women with bacterial vaginosis: a randomized, controlled trial.
AB  - OBJECTIVE: To determine whether treatment of bacterial vaginosis (BV) in early
      pregnancy decreases the risk of preterm delivery and peripartum infectious
      morbidity. METHODS: In this multicenter, randomized, double-masked, placebo
      controlled intervention trial, screening for BV was performed by vaginal Gram
      stain obtained from 5432 healthy women with singleton pregnancies during the
      first antenatal clinic visit at 10--17 weeks' gestation. Bacterial vaginosis
      positive women with no past history of preterm delivery were randomized to a
      single course of treatment with either 2% vaginal clindamycin cream or identical
      placebo cream for 7 days. Repeat Gram stains were taken 1 week after treatment
      and at 30--36 weeks' gestation. Preterm delivery was defined as spontaneous
      delivery before 37 gestational weeks. Peripartum infectious morbidity was defined
      as postpartum endometritis, postpartum sepsis, postcesarean wound infection, or
      episiotomy wound infection, necessitating antimicrobial therapy. According to the
      power analysis, 180 patients were needed for both treatment arms to show a three
      fold difference in the rates of preterm births. RESULTS: The overall prevalence
      of BV was 10.4%. Of all BV-positive women, 375 (66%) were randomized to the
      treatment arms. The primary cure rate was 66% in the clindamycin group; in the
      placebo group, 34% spontaneously cleared BV (odds ratio [OR] 1.9, 95% confidence
      interval [CI] 1.3, 2.8). The rate of preterm deliveries was 5% in the clindamycin
      group and 4% in the placebo group (OR 1.3, 95% CI 0.5, 3.5). The rate of
      peripartum infectious morbidity was 11% in the clindamycin group and 18% in the
      placebo group (OR 1.6, 95% CI 0.9, 2.8). Bacterial vaginosis recurred in 7% of
      women. The rate of preterm deliveries was 15% in this subgroup compared with 2%
      among women who remained BV negative (OR 9.3, 95% CI 1.6, 53.5). CONCLUSION:
      Vaginal clindamycin did not decrease the rate of preterm deliveries or peripartum
      infections, but recurrent or persistent BV increased the risk for these
      complications.

PMID- 11339910
TI  - Multiple lifestyle and psychosocial risks and delivery of small for gestational
      age infants.
AB  - OBJECTIVE: To examine the occurrence of multiple risk behaviors during pregnancy
      among women who delivered a live birth and to examine the risk of delivering
      small for gestational age (SGA) infants for women with multiple risks. METHODS:
      We used data from the Pregnancy Risk Assessment Monitoring System to conduct the
      research. Pregnancy Risk Assessment System is a population-based, mixed-mode
      surveillance system that collects information on maternal behaviors and
      experiences. We used data for 1997 from 13 (n = 19,331) states that had response
      rates of over 70%. We considered ten self-reported individual risk behaviors or
      exposures (eg, smoking, unintended pregnancy) and several demographic variables.
      The main outcome was SGA. RESULTS: Pregnant women engage in or are exposed to
      multiple risks and often these risks are inter-related. The occurrence of
      multiple risks appears to be associated with an increased likelihood of
      delivering an SGA infant. Compared with women with no reported risks or
      exposures, the adjusted odds ratios for delivering an SGA infant were as follows:
      1.29 (95% confidence interval [CI] 0.69, 2.43) for one, 1.86 (95% CI 1.00, 3.44)
      for two, 1.67 (95% CI 0.90, 3.10) for three, 2.06 (95% CI 1.10, 3.89) for four,
      3.53 (95% CI 1.71, 7.30) for five, and 3.82 (95% CI 1.97, 7.41) for six or more
      risks or exposures. CONCLUSION: A large proportion of pregnant women engage in or
      are exposed to multiple risks. Women with a larger number of risks are at greater
      risk for delivering an SGA infant than women with fewer or no risks.

PMID- 11339911
TI  - Second trimester corticotropin-releasing hormone levels in relation to preterm
      delivery and ethnicity.
AB  - OBJECTIVE: To assess the relationship between maternal corticotropin-releasing
      hormone (CRH) levels in second trimester sera, and the risk of preterm delivery
      in an ethnically heterogeneous sample of pregnant women. METHODS: This nested
      case-control study included two case groups (97 women who delivered before 35
      weeks' gestation, 144 who delivered at 35--36 weeks' gestation), and a control
      group (244 women who delivered at or after 37 weeks' gestation) frequency matched
      by ethnicity (black, white) and by alpha-fetoprotein levels (normal, unexplained
      high). Corticotropin-releasing hormone was evaluated in stored maternal sera
      collected at 15--19 weeks' gestation from cases and controls. RESULTS: Delivery
      before 35 weeks' gestation was associated positively with a second trimester,
      ethnic-specific CRH above 1.5 multiples of the median in white women [odds ratio
      (OR) 2.3, 95% confidence interval (CI) 1.1, 5.1] and black women (OR 5.0, 95% CI
      1.8, 13.3). Sensitivity was 29% in whites and 41% in blacks; specificity was 84%
      in whites and 80% in blacks. We estimated the positive and negative predictive
      values to be 6% and 97%, respectively, in white women, and 16% and 93%,
      respectively, in black women. It was also noted that, within case and control
      groups, black women had consistently lower CRH levels than white women.
      CONCLUSION: Factors that lead to a premature increase in placental CRH production
      and are associated with an increased risk of preterm birth are evident as early
      as 15--19 weeks' pregnancy. When considering potential links between stressors,
      placental changes, CRH levels, and preterm birth, it might be important to
      stratify or adjust for ethnicity.

PMID- 11339912
TI  - Polymorphisms within the interleukin-1 beta gene cluster and preeclampsia.
AB  - OBJECTIVE: To identify associations between polymorphisms within the interleukin
      1 beta gene cluster, all of which increase protein expression, and preeclampsia.
      METHODS: We genotyped a Hispanic population (69 women with preeclampsia and 47
      controls) for two polymorphisms of the interleukin-1 beta gene (promoter region
      and exon 5) and one polymorphism of the interleukin-1 receptor antagonist gene in
      intron 2. Clinical data were collected from medical records. Values are given as
      means or medians. Statistical power to identify a difference in occurrence of
      interleukin-1 beta promoter, interleukin-1 beta exon 5, and interleukin-1
      receptor antagonist gene polymorphisms in women with preeclampsia compared with
      controls was 21%, 15.9%, and 30.9%, respectively. RESULTS: We found no
      association between any single polymorphism and occurrence of preeclampsia. Among
      women with preeclampsia, those with polymorphism of interleukin-1 receptor
      antagonist gene had higher mean systolic blood pressure (BP) at admission (178 +/
      33.4 versus 159 +/- 19.5 mmHg, P =.039). When all three polymorphisms combined
      were evaluated, women with preeclampsia and at least three mutant alleles (n = 8)
      had higher mean systolic BP at admission (182 +/- 30 versus 160 +/- 20.5 mmHg, P
      =.009) and increased alanine aminotransferase (67 [10--1024] versus 20 [3--407]
      IU/L, P =.04) and aspartate aminotransferase (119 [25--2239] versus 24 [4--489]
      IU/L, P =.002). At admission, BP in controls was independent of any polymorphism
      identified. CONCLUSION: Although the power of this study was limited, our data do
      not support a role for polymorphisms of the interleukin-1 beta and interleukin-1
      receptor antagonist genes in the pathogenesis of preeclampsia among Hispanic
      women. Our findings do suggest that polymorphisms within the gene cluster might
      influence severity of preeclampsia.

PMID- 11339913
TI  - Plasma volume expansion in early pregnancy.
AB  - OBJECTIVE: To determine the time course of plasma volume expansion in early
      pregnancy. METHODS: We prospectively measured plasma volume by Evans blue dye
      dilution during the menstrual (cycle day 2--3), follicular (cycle day 9--10), and
      luteal phases (cycle day urinary leutinizing hormone [LH] surge plus 9--10) of
      the menstrual cycle and at three additional time points (LH surge + 16 days, LH
      surge + 28 days, and LH surge + 70 days) in women achieving pregnancy. Twenty-one
      subjects were examined during 38 menstrual cycles to establish baseline menstrual
      cycle data. Ten subjects conceived within 1 year of menstrual cycle studies. All
      ten pregnancies were viable and reached the third trimester. Analyses used
      repeated-measures analysis of variance with P <.05 accepted for significance.
      RESULTS: Mean plasma volume was found to change significantly across the period
      of observation (P <.008) in those who conceived. Plasma volume at LH surge + 70
      days (12 menstrual weeks, 2320 +/- 280 mL) was greater than either menstrual
      cycle estimates or early pregnancy estimates of plasma volume. There was no
      difference in plasma volume at LH surge + 16 days (2077 +/- 288 mL) or LH surge +
      28 days (2010 +/- 271 mL) compared with menstrual cycle measurements during the
      menstrual phase (2156 +/- 292 mL), follicular phase (2036 +/- 280 mL), and luteal
      phase (2120 +/- 425 mL). There was no significant difference between those who
      conceived and those who did not in their mean menstrual cycle plasma volume.
      CONCLUSION: Plasma volume expansion in early human pregnancy cannot be identified
      until after the sixth menstrual week. By 12 menstrual weeks, plasma volume has
      expanded by approximately 14% +/- 12% (mean +/- SD) over follicular phase
      measurements.

PMID- 11339915
TI  - Abdominal sacrocolpopexy and anatomy and function of the posterior compartment.
AB  - OBJECTIVE: To assess the effect of abdominal sacrocolpopexy with obliteration of
      the pouch of Douglas on anatomy and function of the posterior compartment.
      METHODS: We prospectively studied 33 consecutive women with pelvic organ prolapse
      who had abdominal sacrocolpopexies [expanded polytetrafluoroethylene (Gore-Tex)]
      with pouch of Douglas obliterations and posterior extensions of mesh, using a
      standardized questionnaire, urodynamic studies, pelvic floor fluoroscopies, and
      vaginal-rectal examinations (Baden-Walker classification). Concomitant
      colpoperineorrhaphy was done if rectoceles remained at rectovaginal examination
      at the end of sacrocolpopexy. The goal was to correct rectoceles
      transabdominally. RESULTS: Thirty-one women returned for follow-up investigations
      after 12--48 months (mean 26 months). Mean age was 61 years (range 41--77 years).
      There was no recurrence of vaginal vault prolapse, enterocele, or anterior rectal
      wall prolapse. Among 28 preoperative rectoceles, 16 recurred (57%) and one
      occurred de novo. Defecation problems (outlet constipation) were present in 21
      women (64%) preoperatively and persisted or were altered in 12 (57%) after
      sacrocolpopexy. Grade of rectocele was associated significantly with symptoms of
      outlet constipation preoperatively, but not postoperatively (P =.002).
      CONCLUSION: Abdominal sacrocolpopexy with obliteration of the pouch of Douglas
      and posterior extension of the mesh was effective for vaginal vault prolapse,
      enterocele, and anterior rectal wall procidentia, but not concomitant rectocele.
      Twenty-eight percent of women described altered defecation with stool stopping
      higher in the rectosigmoid colon ("high outlet constipation"), which might have
      been caused by denervation during rectal mobilization.

PMID- 11339914
TI  - Pelvic floor education after vaginal delivery.
AB  - OBJECTIVE: To assess the effect of pelvic floor education after vaginal delivery
      on pelvic floor characteristics in nulliparous women. METHODS: We examined 107
      nulliparas during pregnancy and at 9 weeks and 10 months after vaginal delivery.
      Methods used included a questionnaire, clinical examination, perineosonography,
      urethral pressure profiles, and intravaginal and intra-anal pressure recordings
      during pelvic floor contraction. After the second examination, the women were
      assigned in alternating manner to either 12 sessions of pelvic floor exercises
      with biofeedback and electrostimulation (n = 51) or no training (n = 56). The two
      groups were compared at the third examination. RESULTS: Stress urinary
      incontinence incidence decreased in 2% of control subjects compared with 19% of
      women who underwent pelvic floor education (P =.002), whereas the incidence of
      fecal incontinence (5% versus 4%, P = 1) and the percentage of women who
      recovered predelivery pelvic floor contraction strength (33% versus 41%, P =.4)
      were no different. We observed no significant differences in bladder neck
      position and mobility, urethral functional length, maximal urethral closure
      pressure, pressure transmission ratio, residual area of continence at stress
      standing, or intravaginal or intra-anal pressures during pelvic floor contraction
      between groups at the third examination. CONCLUSION: Pelvic floor education,
      begun 2 months postpartum, significantly reduced the incidence of stress urinary
      incontinence, but not fecal incontinence or weak pelvic floor. Similarly, bladder
      neck behavior, urodynamic characteristics, intravaginal or intra-anal pressures
      during pelvic floor squeezing also were not modified.

PMID- 11339916
TI  - Cost-effectiveness of universal cystoscopy to identify ureteral injury at
      hysterectomy.
AB  - OBJECTIVE: To evaluate the cost-effectiveness of routine cystoscopy at the time
      of abdominal, vaginal, and laparoscopically assisted vaginal hysterectomy in
      terms of cost per ureteral injury identified and treated. METHODS: Using a
      hospital-based perspective, a decision-analysis model was constructed to estimate
      the outcomes and costs of cystoscopy or no cystoscopy at the time of abdominal
      hysterectomy. A similar model was constructed for vaginal and laparoscopically
      assisted vaginal hysterectomy to account for the cost of conversion to
      laparotomy. Cost estimates were based on estimated costs of Duke University
      Medical Center and from average Medicare reimbursements for similar Diagnostic
      Related Groups from the Health Care Financing Administration. The incidence of
      ureteral injury was obtained from a review of the literature. Sensitivity
      analyses were performed for the following variables: ureteral injury rate, silent
      ureteral injury rate, cost of cystoscopy, and cost of therapeutic interventions.
      We assumed a silent renal death rate of 0%. RESULTS: Routine cystoscopy at
      abdominal hysterectomy was cost-saving above a threshold ureteral injury rate of
      1.5%. At a ureteral injury rate of 0.2%, the marginal increase in the cost of
      routine intraoperative cystoscopy was $108 per abdominal hysterectomy, with an
      associated cost of $54,000 per ureteral injury identified. In comparison, at a
      ureteral injury rate of 2%, routine cystoscopy gave a marginal cost savings of
      $44 per hysterectomy, with a cost savings of $2200 per ureteral injury identified
      intraoperatively. At the baseline ureteral injury rate of 0.5%, routine
      cystoscopy had a marginally increased cost of $83 per hysterectomy, with an
      incremental cost-effectiveness of $16,600 spent per ureteral injury identified.
      The model constructed for vaginal hysterectomy and laparoscopically assisted
      vaginal hysterectomy yielded a threshold ureteral injury rate of 2%, above which
      routine cystoscopy was cost-saving. In both models, the incidence of ureteral
      injury and the cost of readmission were the two variables with the greatest
      influence on cost-effectiveness. CONCLUSION: The cost-effectiveness of routine
      intraoperative cystoscopy depends on the rate of ureteral injury independent of
      the route of hysterectomy. If that rate exceeds 1.5% for abdominal hysterectomy
      and 2% for vaginal or laparoscopically assisted vaginal hysterectomy, then
      routine cystoscopy is cost-effective.

PMID- 11339917
TI  - Psammoma bodies in cervicovaginal smears.
AB  - OBJECTIVE: To estimate the prevalence of psammoma bodies in routine cervical
      cytology specimens and describe clinical diagnoses associated with them in pre-
      and postmenopausal women. METHODS: We identified all reports that contained
      psammoma bodies from a retrospective review of 34,816 cytology reports over 4
      consecutive years from the computerized pathology database at Yale New-Haven
      Medical Center. Slides were reviewed to confirm and qualify psammoma bodies.
      Medical records of women with psammoma bodies were reviewed and information on
      follow-up was collected. RESULTS: We identified 18 women with psammoma bodies on
      their Papanicolaou smears. The median age was 49.5 years (range 17--78 years).
      Seven of eight postmenopausal women had gynecologic malignancies. Five presented
      with postmenopausal bleeding and had uterine serous or clear-cell carcinomas. One
      presented with a pelvic mass that was ovarian serous carcinoma. Another had a
      serous carcinoma of the fallopian tube with only psammoma bodies on Papanicolaou
      smears. Only one of the remaining 11 nonmalignant cases was a postmenopausal
      woman. CONCLUSION: The prevalence of psammoma bodies in consecutively screened
      Papanicolaou smears was 18 of 34,816. Psammoma bodies on Papanicolaou smears are
      ominous in postmenopausal women. Their presence in asymptomatic premenopausal
      women warrants further evaluation, but not necessarily surgical exploration.

PMID- 11339918
TI  - Incisional hernia in gynecologic oncology patients: a 10-year study.
AB  - OBJECTIVE: To evaluate the independent contribution of clinical and
      constitutional factors in the development of early and late incisional hernias in
      women undergoing surgery for uterine cancer. METHODS: Over 10 years, patients
      undergoing extended abdominal hysterectomy for cervical or endometrial
      malignancies through a vertical incision were followed for the identification of
      incisional hernias. Logistic regression and survival analyses were used for
      statistics. RESULTS: Four hundred fifty-five women were included in the study, 77
      of whom (16.9%) developed incisional hernias. The median (range) body mass index
      was higher in women who developed an incisional hernia than in those who did not
      (28 [19--44] kg/m(2) versus 24 [16--41] kg/m(2); P <.01). The frequencies of
      diabetes (14.3% versus 4.8%; P <.01), wound sepsis (10.4% versus 1.3%; P <.05),
      and fascial closure with interrupted sutures (70.1% versus 55.6%; P <.05) were
      significantly higher in women with incisional hernia than in those without.
      Multiple logistic regression revealed that, after adjustment for confounding
      variables, the only factors associated with incisional hernia formation within 1
      year from the operation were body mass index above 27 kg/m(2) (odds ratio [OR]
      3.68; 95% confidence interval [CI] 1.38, 9.81; P <.01) and wound infection (OR
      5.05; 95% CI 1.39, 18.37; P <.01), whereas the factors associated with incisional
      hernia formation at least 3 years after surgery were diabetes (OR 6.68; 95% CI
      2.02, 22; P <.01) and wound infection (OR 8.55; 95% CI 1.54, 47.5; P <.01). For
      hernia developing after 5 years (OR 8.32; 95% CI 1.41, 55.65; P <.05) and 8 years
      (OR 49.52; 95% CI 2.72, 907.14; P <.01), the only significant association was
      found with diabetes. CONCLUSION: Late incisional hernia formation does not depend
      on conditions present at the time of operation or on surgical technique. Other
      factors such as diabetes seem to play an important role in the development of
      late incisional hernia.

PMID- 11339919
TI  - Population-based study of microinvasive adenocarcinoma of the uterine cervix.
AB  - OBJECTIVE: To analyze lymph node status and survival rates of women with
      microinvasive cervical adenocarcinoma (International Federation of Gynecology and
      Obstetrics stages IA(1) and IA(2)). METHODS: The Surveillance, Epidemiology, and
      End Results (SEER) Public-Use Database was used to identify cases of
      microinvasive cervical adenocarcinoma diagnosed between 1988 and 1997. Variables
      analyzed included stage, extent of surgery, lymph node status, radiation therapy,
      and age. Statistics included analysis of trends, analysis of variance, log-rank
      test, one-sided binomial confidence interval estimation, and power analysis.
      RESULTS: Among 301 reported cases, 131 had stage IA(1) and 170 IA(2) disease.
      Simple hysterectomies were done in 54 women with IA(1) and 64 with IA(2) disease
      and radical hysterectomies were done in 50 and 83 women, respectively. Only one
      of 140 women who had lymphadenectomy had a single positive lymph node. There were
      four tumor-related deaths (one with IA(1), and three with IA(2) disease). There
      were no deaths among 96 women (47, IA(1); 49, IA(2)) treated by simple
      hysterectomy alone. The mean follow-up was 46.5 months (range 1--119). The
      censored survival rate was 98.7% overall (99.2% IA(1), 98.2% IA(2)). Power
      analysis estimated that 720 patients would be required in each group to detect a
      2% difference in survival. Using one-sided 95% confidence interval estimations,
      the risk-adverse events rate for IA(1) was no more than 3.57%, and 4.50% for
      IA(2) disease. CONCLUSION: Prognosis is excellent for microinvasive
      adenocarcinoma of the uterine cervix. In 96 cases (31.9%), simple hysterectomy
      alone proved adequate.

PMID- 11339920
TI  - Vaginal hysterectomy as primary treatment of endometrial cancer in medically
      compromised women.
AB  - OBJECTIVE: To study the survival, rates and patterns of recurrence, and
      perioperative morbidity in medically compromised women with endometrial cancer
      treated by primary vaginal hysterectomy. METHODS: Fifty-one patients with
      endometrial cancer treated initially by vaginal hysterectomy between 1977 and
      1999 were identified at the University of California, Irvine Medical Center and
      affiliated hospitals. Data were retrieved from hospital and office records.
      Statistical analysis, including Kaplan-Meier methods, was performed and the
      disease-specific survival rates were estimated. This study has 80% power to
      demonstrate a greater than 20% improvement in 5-year survival over historical
      controls. RESULTS: Fifty-one women with uterine carcinoma clinically confined to
      the uterus underwent primary vaginal hysterectomy with (n = 26) or without (n =
      25) salpingo-oophorectomy. Eighty-four percent were obese with a body mass index
      greater than 27. Additional risk factors for surgical complications included
      hypertension (57%), diabetes mellitus (27%), and cardiovascular disease (18%).
      One-third of patients had three or more risk factors. Surgical morbidity included
      one episode of acute hemorrhage necessitating transfusion and abdominal
      exploration. Blood transfusions were given to four additional patients. There
      were no perioperative deaths. Five women recurred and expired at a median of 13
      months (range 3--53 months) after surgery. The 3- and 5-year disease-specific
      survival rates were 91.4% and 88.0%, respectively. CONCLUSION: Vaginal
      hysterectomy for the initial treatment of early-stage endometrial cancer is
      associated with a high rate of cure and minimal morbidity. Thus, it may be
      considered a reasonable alternative to the abdominal approach in medically
      compromised women.

PMID- 11339921
TI  - Vaginal hysterectomy for enlarged uteri, with or without laparoscopic assistance:
      randomized study.
AB  - OBJECTIVE: To compare short-term results of vaginal hysterectomy (VH) with those
      of laparoscopically assisted vaginal hysterectomy (LAVH) in women with enlarged
      uteri. METHODS: Eighty women referred for abdominal hysterectomies for benign
      disease were assigned randomly to vaginal hysterectomy or LAVH. Inclusion
      criteria were uterine size larger than 280 g and one or more of the following
      traditional contraindications of vaginal hysterectomy: previous pelvic surgery,
      history of pelvic inflammatory disease, moderate or severe endometriosis,
      concomitant adnexal masses, indication for adnexectomy, and nulliparity without
      uterine descent. RESULTS: There were no differences in patients' mean age,
      parity, rate of postmenopausal state, previous pelvic surgery, preoperative
      hemoglobin levels, and mean uterine weight. Indications for surgery were similar
      between groups. No difference was found in the mean +/- standard deviation (SD)
      uterine weight (range) between vaginal hysterectomy and LAVH groups (424 +/- 211
      g [280--930 g] and 513 +/- 360 g [290--1560 g]), respectively. Except for one
      bladder injury in the laparoscopic group (injury treated laparoscopically), there
      were no other major complications. Complication rates in vaginal and laparoscopic
      groups were 15% and 37.5%, respectively (P <.05). Mean operating time was shorter
      in the vaginal than the laparoscopic group (108 +/- 35 minutes and 156 +/- 50
      minutes, respectively [P <.001]). There was no difference in first day hemoglobin
      level drops or hospital stays between groups. CONCLUSION: Vaginal hysterectomy
      can be successful even in women with enlarged uteri and other conditions
      considered by some to contraindicate the operation. Laparoscopically assisted
      vaginal hysterectomy offered no advantages over the standard vaginal
      hysterectomy.

PMID- 11339922
TI  - Primary pelvic non-Hodgkin's lymphoma.
AB  - OBJECTIVE: To describe five cases of primary pelvic non-Hodgkin's lymphoma, a
      rare gynecologic malignancy. METHODS: The charts of five women with primary
      pelvic non-Hodgkin's lymphoma were reviewed. Histologic classification was based
      on the Working Formulation, and staging was based on the Ann Arbor system.
      Disease status was monitored with physical examination and imaging studies.
      RESULTS: During a 10-month period, five women were diagnosed with primary pelvic
      non-Hodgkin's lymphoma, including one parasacral, one uterine, one vaginal, and
      two ovarian tumors. Presentations included abdominal and pelvic pain, abdominal
      and pelvic mass, and abnormal vaginal bleeding. Treatment included combination
      chemotherapy, with or without radiation. Four patients were alive and disease
      free 20--33 months after therapy. CONCLUSION: Primary pelvic non-Hodgkin's
      lymphoma may present like other more common gynecologic cancers. It should be
      considered in the differential diagnosis of gynecologic malignancy.

PMID- 11339923
TI  - Predictors of complications and hospital stay in gynecologic cancer surgery.
AB  - OBJECTIVE: To test the hypothesis that comorbid medical conditions can predict
      length of hospital stay and incidence of postoperative complications. METHODS: We
      reviewed the medical records of 187 women who had surgery for known or suspected
      gynecologic malignancies during 1996 and 1997, and 179 were included in the
      present study. Information on each woman's comorbid medical conditions, surgical
      history, surgicopathologic cancer diagnosis, American Society of
      Anesthesiologists' classification, surgical procedures, and postoperative
      complications was collected and analyzed. RESULTS: Women with two or more
      comorbid medical conditions had significantly longer mean hospital stays (8.62
      days) than those with none or one comorbid medical condition (6.43 days) (P
      <.001). Women with two or more postoperative complications had significantly
      longer mean hospital stays (11.88 days) than those with none or one complication
      (6.02 days) (P <.001). Women with two or more postoperative complications also
      had significantly more comorbid medical conditions (mean 2.5) than those with
      none or one complication (mean 1.7) (P <.001). The American Society of
      Anesthesiologists class also was a significant predictor of postoperative
      complications and length of hospitalization. Age over 60 years also was
      associated with statistically significant increase in comorbid medical conditions
      and significantly longer hospitalizations. CONCLUSION: Our findings indicated
      that certain high-risk patients can be identified before hospital admission based
      on comorbid medical conditions. Certain risk indices, such as the American
      Society of Anesthesiologists classification score, also can predict postoperative
      complications and length of hospital stay. This information can be used to
      coordinate preoperative and postoperative hospital care and be a reference for
      certain future disease management systems.

PMID- 11339924
TI  - Malignant potential of positive peritoneal cytology in endometrial cancer.
AB  - OBJECTIVE: To investigate the malignant potential of positive peritoneal cytology
      in endometrial cancer. METHODS: Fifty patients with clinical stage I-II
      endometrial cancer in whom the disease was completely surgically resected and
      positive peritoneal smears were found at surgery formed the study population. In
      these patients, a tube for cytologic analyses was inserted into the peritoneal
      cavity when closing the abdomen. The peritoneal cavity was irrigated with
      physiologic saline, and washings were obtained through the tube 7 and 14 days
      after the operation. RESULTS: Persistence of positive peritoneal cytology was
      observed in four of seven patients with adnexal metastasis, zero of nine patients
      with nodal disease, and one of 34 patients with disease confined to the uterus,
      for a total of 10% (5 of 50). In the remaining 45 (90%) patients, no malignant
      cells were found in any of the washings. CONCLUSION: The current series suggests
      that endometrial cancer cells found in the peritoneal cavity usually disappear
      within a short time and seem to have a low malignant potential. It also seems
      that only malignant cells from special cases, such as adnexal metastasis, may be
      capable of independent growth, and are possibly associated with intraperitoneal
      recurrence.

PMID- 11339925
TI  - Pregnancy outcomes after prenatal diagnosis of aneuploidy.
AB  - OBJECTIVE: To determine the benefits of antenatal diagnoses of fetal aneuploidy
      in women who continued their pregnancies. METHODS: A questionnaire was mailed to
      51 mothers of children with aneuploidy. Women whose fetuses were diagnosed
      prenatally comprised the study group and those whose infants were diagnosed at
      birth were controls. Outcomes measured included an assessment of pregnancy
      management, neonatal outcome, subjective measures of depression and anxiety, and
      evaluation of women's emotional and physical experience of the pregnancy. For
      outcomes measured by nonparametric survey questions, 20 women were needed in each
      arm to achieve a power of 80% to detect a 2-point difference on a 6-point scale;
      for our neonatal outcomes, 100 women were needed in each arm to achieve 80% power
      to detect a difference in length of stay (less than 1 week versus greater than 1
      week) or need for surgery. RESULTS: Thirty-eight women (75%) responded. Most
      (86%) had children with trisomy 21. Seventeen women (45%) received their child's
      diagnosis at birth; 21 (55%) had prenatal diagnoses. Demographic measures were
      similar except that women with prenatal diagnoses attended religious services
      more frequently (1--3 times per month versus once to several times per year, P
      =.04). Women with prenatal diagnosis had better perceptions of their physical
      experience of pregnancy (median score of 10 versus 6 on a 10-point visual analog
      scale, P =.005) and their emotional experience of the birth (median score of 7.5
      versus 2, P =.001). Mental Health Inventory scores were similar between groups.
      Neonates without prenatal diagnoses were more likely to be transferred to
      tertiary centers after birth (70% versus 24%, P =.004); lengths of hospital stays
      and need for surgery were similar. Seventy-one percent (95% confidence interval
      [CI] 48, 89%) of women with prenatal diagnoses said they would have done nothing
      differently in the pregnancy compared with 29% (95% CI 10, 56%) of women with
      diagnoses at birth. CONCLUSION: Early knowledge of fetal aneuploidy is beneficial
      to women who continue their pregnancies. These results might be useful when
      counseling women who do not intend to terminate abnormal pregnancies, but are
      considering prenatal diagnosis.

PMID- 11339926
TI  - Macrosomia associated with maternal serum insulin-like growth factor-I and -II in
      diabetic pregnancy.
AB  - OBJECTIVE: To determine the possible relation between maternal serum insulin-like
      growth factor I and II (IGF-I and IGF-II) in women with insulin-dependent
      diabetes mellitus and fetal macrosomia. METHODS: This was a prospective,
      observational study of 45 pregnant women with insulin-dependent diabetes mellitus
      without overt nephropathy, examined in an outpatient, antenatal diabetic clinic.
      Maternal venous serum samples were collected from week 14 every fourth week until
      week 30, and every other week until delivery. Levels of IGF-I and -II were
      measured in maternal serum by immunoassays. The repeated measurements were tested
      with two-way analysis of variance. The outcome measures were birth weight and
      serum IGF-I, IGF-II, IGF binding protein (BP)-3, and IGFBP-3 proteases. Before
      the study, minimum sampling size was calculated as 14 subjects in each group if a
      difference in IGF-I of 50 microg/L was to be detected with an estimated standard
      deviation of 40, a two-sided P value (alpha) of.05, and a power of 90 (beta =.1).
      RESULTS: Increasing levels of IGF-I and -II were significantly associated with
      the birth-weight groups: The higher the birth-weight ratio, the higher the levels
      of IGF-I and -II (P <.01). CONCLUSION: Macrosomia in diabetic pregnancy is
      associated with high levels of maternal IGF-I and -II.

PMID- 11339927
TI  - Influence of gestational age and maternal height on fetal femur length
      calculations.
AB  - OBJECTIVE: To determine whether current methods of detecting Down syndrome based
      on fetal femur length calculations are influenced by gestational age or maternal
      height. METHODS: Four formulas were used to calculate expected femur length (FL)
      based on the fetal biparietal diameter (BPD) between 15 0/7 weeks' gestation and
      19 6/7 weeks' gestation. For each gestational age, the BPD:FL ratio for women
      shorter than one standard deviation (SD) below the mean height was compared with
      the ratio for women taller than one SD above the mean height. A measured:expected
      FL ratio of 0.91 or less and a BPD:FL ratio greater than 1.5 SD above the mean
      was considered abnormal. RESULTS: The four formulas used to calculate
      measured:expected FL ratios were significantly more likely to be abnormal at 15-
      16 weeks' gestation, compared with 18-19 weeks' gestation (P <.05). Maternal
      height correlated with femur lengths at 18 and 19 weeks' gestation (P <.05) but
      not at earlier gestational ages. At 18 and 19 weeks' gestation, women shorter
      than one SD below the mean were twice as likely to have an abnormal BPD:FL ratio
      compared with women taller than one SD above the mean (relative risk 2.38; 95%
      confidence interval 1.21, 4.69). CONCLUSION: Early gestational age increases a
      woman's risk of having an abnormal measured:expected FL ratio, whereas short
      stature increases a woman's risk of having an abnormal BPD:FL ratio at later
      gestational ages. These findings indicate that risk assessment for fetal Down
      syndrome for such patients might be inaccurate. (Obstet Gynecol 2001;97:742-6.

PMID- 11339928
TI  - Clinical significance of fetal heart rate tracings during the second stage of
      labor.
AB  - OBJECTIVE: To examine the significance of abnormal fetal heart rate (FHR)
      patterns during the second stage of labor in terms of pregnancy outcome. METHODS:
      A prospective observational study comparing women who had abnormal FHR patterns
      during the second stage of labor with women who demonstrated normal FHR patterns.
      RESULTS: Abnormal second-stage FHR patterns were found in 420 tracings (75%),
      whereas 140 tracings (25%) were normal. In a multivariable analysis, nulliparity
      (odds ratio [OR] 2.5; 95% confidence interval [CI] 1.5, 4.2), cord problems (OR
      1.8; 95% CI 1.03, 3.3), and male sex (OR 1.5; 95% CI 1.01, 2.2) were independent
      factors affecting the occurrence of abnormal second-stage FHR patterns. Patients
      with abnormal tracings had significantly higher rates of operative delivery
      compared with patients with normal tracings. The newborns from the case group had
      significantly higher percentages of Apgar scores lower than 7 at 1 minute,
      arterial pH lower than 7.2, and base deficit of 12 mmol/L or higher, and six were
      admitted to the intensive care unit (ICU). A multiple logistic regression model
      found second-stage late decelerations, bradycardia less than 70 beats per minute,
      and the presence of abnormal FHR patterns during the first stage of labor to be
      independently associated with fetal acidosis (determined by pH less than 7.2 and
      base deficit greater than 12 mmol/L). CONCLUSION: Late decelerations, bradycardia
      less than 70 beats per minute, and abnormal FHR patterns during the first stage
      of labor might jeopardize fetal well-being, and expedited delivery should be
      considered.

PMID- 11339929
TI  - Postnatal screening for thrombophilia in women with severe pregnancy
      complications.
AB  - OBJECTIVE: To examine the prevalence of maternal thrombophilia in women with
      severe preeclampsia/eclampsia, placental abruption, fetal growth restriction, and
      unexplained stillbirth. METHODS: We studied 102 women who had pregnancy
      complications and 44 healthy women with uncomplicated pregnancies. All women were
      tested 10 weeks postpartum for mutations of factor V Leiden,
      methylenetetrahydrofolate reductase (MTHFR) C677T, and G20210A prothrombin gene;
      deficiencies of protein C, protein S, and antithrombin III; and the presence of
      lupus anticoagulant and anticardiolipin antibodies. We aimed to recruit 100 cases
      and 300 controls to detect a 10% difference in thrombophilia between the groups.
      However, we were able to recruit only 44 controls. RESULTS: Abnormal
      thrombophilia screen was found in 54 women with pregnancy complications (53%) and
      in 17 women (39%) with normal pregnancies (odds ratio [OR] 1.8; 95% confidence
      interval [CI] 0.87, 3.67). Mutations encoding for factor V Leiden, G20210A
      prothrombin gene, and MTHFR C677T (homozygous) were identified in 18% of women
      with complications compared with 16% of controls (OR 1.1; 95% CI 0.44, 2.94).
      Activated protein C resistance, not due to factor V Leiden mutation, was the most
      common thrombophilic defect, found in 26% of women with pregnancy complications
      compared with 18% of controls (OR 1.5; 95% CI 0.63, 3.73). Twenty women with
      complications (20%) had multiple thrombophilic defects compared with four
      controls (9%) (OR 2.4; 95% CI 0.78, 7.61). CONCLUSION: In our cohort of women
      with pregnancy complications, maternal thrombophilia was less common than
      previously thought, and multiple thrombophilias were not a major additional risk
      factor.

PMID- 11339930
TI  - Acute respiratory distress syndrome in pregnancy and the puerperium: causes,
      courses, and outcomes.
AB  - OBJECTIVE: To describe causes, courses, complications, and outcomes of patients
      with pregnancy-associated acute respiratory distress syndrome (RDS). METHODS:
      Twenty-eight women with ARDS during pregnancy or within a week postpartum formed
      the study population. Eight cases had been reported previously. Charts were
      abstracted for maternal demographics, etiology, and treatment of acute RDS, and
      maternal outcomes. For antepartum acute RDS, newborn charts were also reviewed.
      RESULTS: The incidence of acute RDS, excluding maternal transports, was one per
      6277 deliveries or 0.016% (95% confidence interval [CI] 0, 0.027%). Leading
      causes were infection (12 cases), preeclampsia or eclampsia (seven cases), and
      aspiration (three cases). Eleven mothers died, a maternal mortality rate of 39.3%
      (CI 21.5%, 59.4%). Six of eight women who were ventilated for over 14 days
      survived. Nine of the acute RDS cases might have been preventable. Ten mothers
      with living fetuses were ventilated during the third trimester; nine delivered
      within 4 days. Among six infants delivered because of fetal heart rate
      abnormalities, one died and at least three had evidence of asphyxia. CONCLUSIONS:
      Acute RDS occurs more frequently in pregnancy than the 1.5 cases per 100,000 per
      year reported for the general population. Prolonged ventilator support is
      warranted. The high rate of perinatal asphyxia in infants who have fetal heart
      rate abnormalities supports a strategy of expeditious delivery during the third
      trimester.

PMID- 11339931
TI  - First-birth cesarean and placental abruption or previa at second birth(1).
AB  - OBJECTIVE: To assess the association between first-birth cesarean delivery and
      second-birth placental abruption and previa. METHODS: We conducted a population
      based, retrospective cohort analysis using data from the Washington State Birth
      Events Record Database. The study cohort included all primiparas who gave birth
      to live singleton infants in nonfederal short-stay hospitals from January 1,
      1987, through December 31, 1996, and who had second singleton births during the
      same period (n = 96,975). Odds ratios (ORs) and 95% confidence intervals (CIs)
      were calculated for placental abruption or previa at second births associated
      with first-birth cesareans. RESULTS: Among our study cohort, abruptio placentae
      complicated 11.5 per 1000 and placenta previa 5.2 per 1000 singleton deliveries
      at second births. In logistic regression analyses adjusted for maternal age,
      women with first-birth cesareans had significantly increased risk of abruptio
      placentae (OR 1.3, 95% CI 1.1, 1.5), and placenta previa (OR 1.4, 95% CI 1.1,
      1.6) at second births, compared with women with prior vaginal deliveries.
      CONCLUSION: We found moderately increased risk of placental abruption and previa
      as a long-term effect of prior cesarean delivery on second births.

PMID- 11339932
TI  - Anal sphincter damage after vaginal delivery using three-dimensional
      endosonography.
AB  - OBJECTIVE: To determine the incidence and functional consequences of external
      sphincter trauma compared with other perineal structures using a novel imaging
      technique, three-dimensional endosonography. METHODS: Fifty-five nulliparous
      women (mean age 30 years, range 18--47 years) had three-dimensional anal
      endosonography, anal manometry, and questionnaire assessment of continence at a
      median gestation of 33 weeks (23--42 weeks) and 10 weeks (7--22 weeks) after
      delivery. RESULTS: There was ultrasound evidence of postpartum trauma in 13 of 45
      women who had a vaginal delivery (29%, confidence interval [CI] 16%, 44%),
      involving the external sphincter in five (11%, CI 4%, 24%), the puboanalis in
      nine (20%, CI 10%, 35%), and the transverse perineii in three (7%, CI 1%, 18%).
      In four, more than one structure was damaged. External sphincter trauma was
      associated with a significant decrease in squeeze pressure (P =.035) and an
      increase in incontinence score (P =.02) compared with those without trauma. Tears
      to the puboanalis or transverse perineii only did not affect pressure or
      incontinence scores. Coronal imaging of the external anal sphincter was a useful
      adjunct to the assessment of trauma. CONCLUSION: The overall incidence of trauma
      to the sphincter complex was similar to that of previous reports, although actual
      damage to the external sphincter was less common and represented the only
      functionally significant component.

PMID- 11339933
TI  - Maternal serum triglyceride at 24--32 weeks' gestation and newborn weight in
      nondiabetic women with positive diabetic screens.
AB  - OBJECTIVE: To determine whether elevated midpregnancy maternal serum lipid levels
      predict newborn weight at term and the risk of large for gestational age (LGA)
      infants in women with positive diabetic screen but normal glucose tolerance test.
      METHODS: Japanese gravidas who had positive diabetic screens and normal 75-g oral
      glucose tolerance tests (GTT) at 24--32 weeks were enrolled. Subjects with
      complications, including diabetes, hypertension, or fetal anomalies were
      excluded, as were women with multifetal gestations. Fasting serum triglyceride,
      free fatty acids, and total cholesterol levels were measured at the time of GTT.
      We tested the association between maternal variables and birth weight by
      univariable analysis. We used multivariable analysis to test whether the
      association between fasting lipids and birth weight was independent of
      prepregnant maternal body mass index (BMI), maternal weight gain during
      pregnancy, and plasma glucose levels at GTT. We also used multiple logistic
      regression analysis to determine whether maternal hyperlipidemia, defined as more
      than the 75th percentile of each lipid, is a risk factor for having an LGA
      infant. RESULTS: We enrolled 146 subjects. Among measured maternal lipids, only
      triglyceride levels correlated with birth weight in univariable analysis (r =
      0.22, P =.009). Birth weight also was correlated with prepregnant maternal BMI (r
      = 0.18, P =.04) and fasting plasma glucose levels (r = 0.17, P =.04). The
      association between maternal fasting triglyceride level and birth weight remained
      significant after adjusting for prepregnant BMI, maternal weight gain, fasting
      plasma glucose levels, fetal gender, and gestational age at birth (P =.01).
      Logistic regression analysis showed that fasting maternal hypertriglyceridemia
      (over 259 mg/dL) was the significant predictor of LGA infants, independent of
      prepregnant BMI, maternal weight gain, and maternal plasma glucose levels (odds
      ratio 11.6; 95% confidence interval 1.1, 122; P =.04). CONCLUSION: In women with
      positive diabetic screens but normal GTTs, fasting triglyceride levels at 24-32
      weeks correlated positively with newborn weight at term, independent of maternal
      plasma glucose levels and obesity. Maternal fasting serum triglyceride levels in
      midpregnancy might be an independent predictor of fetal macrosomia in those
      women.

PMID- 11339934
TI  - Impact of increasing Papanicolaou test sensitivity and compliance: a modeled cost
      and outcomes analysis.
AB  - OBJECTIVE: To model the impact of increasing screening compliance or implementing
      liquid-based cytology in populations with known compliance patterns and risk
      profiles on rates of detection of cervical precancers. METHODS: An adaptation of
      a time-varying Markov model was used to follow a theoretic cohort of 100,000
      women from age 20 through age 80. Separate analyses of all women, white, and
      black women were completed using three compliance rates (self-reported, Healthy
      People 2000, and Healthy People 2010 compliance) and two Papanicolaou test
      sensitivities (conventional Papanicolaou smear and liquid-based cytology).
      RESULTS: All populations benefited from both increased compliance and liquid
      based cytology use. Increasing compliance to Healthy People 2010 goals resulted
      in 23%, 21.7%, and 17% reductions in cervical cancer incidence for all women,
      white, and black women, respectively. Substituting liquid-based cytology for
      traditional Papanicolaou smear collection and processing with no change in
      compliance resulted in 32%, 32%, and 33% reductions in cervical cancer incidence
      for the same three subpopulations. In addition, cost-effectiveness of the liquid
      based technology indirectly related to the risk profile of the population: for
      black women, the cost-effectiveness ratio was $10,335 per life year saved,
      whereas for white women, the ratio was $17,967 per life year saved. CONCLUSION:
      Using liquid-based cytology in all populations would be cost-effective in
      improving outcomes from cervical cancer. In high-risk populations, this new
      technology may represent the most cost-effective approach to improve cervical
      cancer outcomes.

PMID- 11339935
TI  - Cost savings from emergency contraceptive pills in Canada.
AB  - OBJECTIVE: To estimate cost savings from emergency contraceptive pills in Canada.
      METHODS: We modeled cost savings when a single emergency contraceptive treatment
      was provided after unprotected intercourse and when women were provided emergency
      contraceptive pills in advance. RESULTS: Each dollar spent on a single treatment
      saved $1.19--$2.35 (in Canadian currency), depending on the regimen and on
      assumptions about savings from costs avoided by preventing mistimed births. The
      dedicated products Preven (Shire Canada, Inc., Oakville, Ontario) and Plan B
      (Paladin Labs, Inc., Montreal) were cost-saving even under the least favorable
      assumption that mistimed births prevented today occur 2 years later. Each dollar
      spent on advance provision of Preven saved $1.24--$12.23, depending on the
      regular contraception method, on how consistently emergency contraception was
      used when needed, and on whether mistimed births were averted forever or simply
      delayed. Plan B was almost always cost-saving, although less so. CONCLUSION:
      Emergency contraception was cost-saving whether provided when the emergency
      occurred or in advance to be used as needed. More extensive use of emergency
      contraception could save considerable medical costs by reducing unintended
      pregnancies.

PMID- 11339936
TI  - Effect of gender on the obstetric-gynecologic work force.
AB  - As increasing numbers of female physicians enter the specialty of obstetrics and
      gynecology, their productivity (defined as producing goods and services) as
      compared with male physicians becomes important. Data from the American Medical
      Association socioeconomic survey and from a survey of ACOG Fellows indicate that,
      as a group, female physicians in the specialty are approximately 85% as
      productive as male physicians in the specialty. ACOG data for physician net
      income validate the productivity calculations (P <.03). The increasing numbers of
      female physicians in the specialty will lead to a decreasing aggregate
      productivity. At the same time, the increasing numbers of women of all ages in
      the United States will lead to a decline in the available obstetrician
      gynecologist work force beginning in the year 2010.

PMID- 11339937
TI  - Chemistry and properties of starch based desiccants.
AB  - Desiccants currently used in industry include molecular sieves, lithium chloride,
      silica gel, and corn grits. Of these, only corn grits (a form of ground corn) are
      biodegradable and derived from a renewable resource. A major component of the
      corn grits, starch, is the primary adsorptive material in the corn grits. Other
      polysaccharides, including cellulose and hemicellulose also have adsorptive
      properties. The use of alpha-amylase (EC 3.2.1.1) to modify porosity and surface
      properties of starch resulted in materials with enhanced water sorption
      properties compared to the native material. This paper reviews the chemical and
      structural properties of starch, corn grits, and cellulose-based scaffolds on
      which starch can be affixed, in order to attain structures that might someday
      find uses in a range of desiccant applications for industrial, commercial, and
      residential processes.

PMID- 11339938
TI  - The catalytic domain of a Piromyces rhizinflata cellulase expressed in
      Escherichia coli was stabilized by the linker peptide of the enzyme.
AB  - Analysis of a carboxymethyl-cellulase clone isolated from the cDNA library of the
      ruminal fungus, Piromyces rhizinflata 2301, revealed that the clone encoded a
      polypeptide containing a cellulase catalytic domain, designated CelAcd. CelAcd
      was flanked by a 28-amino acid linker peptide at the N-terminus and linked to a
      dockerin domain by a 7-amino acid linker at the C-terminus. CelAcd showed
      homology with the family 5 of glycosyl hydrolases. CelAcd plus the linker
      peptides at both termini (designated CelcdN'C') was expressed in Escherichia coli
      and the purified enzyme was characterized. The feature of particular interest of
      CelcdN'C' was its bifunctional endo- and exo-glucanase activity, demonstrated by
      its ability to hydrolyse carboxymethyl cellulose (CMC) and pNP-beta-D
      cellobioside. Furthermore, CelcdN'C' exhibited relatively high ability to degrade
      both microcrystalline Avicel and filter paper. CelcdN'C' also showed activity
      against barley beta-glucan, Lichenin and oat spelt xylan. The optimal activity
      conditions for CelcdN'C' with CMC as the substrate were pH 5.5 and 50 degrees C.
      Fifty percent of the enzyme activity was lost when CelcdN'C' was treated at 55
      degrees C for 10 min. CelcdN'C' retained more than 10% enzyme activity after
      being heated under 90 degrees C for 10 min. Deletion of the N-terminal flanking
      linker of CelcdN'C' (the resulting protein was designated CelcdC') did not alter
      the enzymatic function of the catalytic domain. However, the thermal stability of
      CelcdC' was dramatically reduced. We conclude that the N-terminal flanking linker
      of CelAcd stabilizes the enzyme protein.

PMID- 11339939
TI  - Encapsulation of tannase for the hydrolysis of tea tannins.
AB  - Tannase was encapsulated in alginate, chitosan, carrageenan or pectin gel
      matrices, and in the case of alginate, coated with high or low molecular weight
      chitosan to reduce enzyme release. Cross-linking with glutaraldehyde also
      improved enzyme retention. Active enzyme preparations were obtained, although
      carrageenan gels were unstable in tea. Tannase activity was evaluated by
      reduction in centrifugable (flocculated) tea solids, and a reduction in tea cream
      measured turbidimetrically after removal of flocculated solids. Tannin
      interactions with the polysaccharide gels increased the level of centrifugable
      solids (flocculent) in the tea. An optimum bead formulation consisted of an
      alginate core, coated with chitosan and cross-linked with glutaraldehyde. Both
      core and coating materials contained active enzyme. Beads were prepared in a
      single step procedure involving extrusion of alginate/tannase solution into a
      hardening bath containing tannase-loaded, chitosan solution. Tannase retained
      hydrolytic activity through three successive batch cycles, for a total period of
      39h processing, and tea cream was visibly removed by treatment with the
      immobilized tannase. Activity remained stable during 1-month bead storage under
      refrigeration.

PMID- 11339940
TI  - Sucrose hydrolysis by thermostable immobilized inulinases from aspergillus
      ficuum.
AB  - The possibility of using thermostable inulinases from Aspergillus ficuum in place
      of invertase for sucrose hydrolysis was explored. The commercial inulinases
      preparation was immobilized onto porous glass beads by covalent coupling using
      activation by a silane reagent and glutaraldehyde before adding the enzyme. The
      immobilization steps were optimized resulting in a support with 5,440 IU/g of
      support (sucrose hydrolysis) that is 77% of the activity of the free enzyme.
      Enzymatic properties of the immobilized inulinases were similar to those of the
      free enzymes with optimum pH near pH 5.0. However, temperature where the activity
      was maximal was shifted of 10 degrees C due to better thermal stability after
      immobilization with similar activation energies. The curve of the effect of
      sucrose concentration on activity was bi-phasic. The first part, for sucrose
      concentrations lower than 0.3 M, followed Michaelis-Menten kinetics with apparent
      K(M) and Vm only slightly affected by immobilization. Substrate inhibition was
      observed at values from 0.3 to 2 M sucrose. Complete sucrose hydrolysis was
      obtained for batch reactors with 0.3 and 1 M sucrose solutions. In continuous
      packed-bed reactor 100% (for 0.3 M sucrose), 90% (1 M sucrose) or 80% sucrose
      conversion were observed at space velocities of 0.06-0.25 h(-1). The operational
      half-life of the immobilized inulinases at 50 degrees C with 2 M sucrose was 350
      days.

PMID- 11339941
TI  - Comparison of two assay procedures for lignin peroxidase.
AB  - The most widely accepted assay for detecting lignin peroxidase, based on the
      oxidation of veratryl alcohol to veratraldehyde, suffers from some drawbacks. At
      310 nm, the wavelength at which the assay is performed, some other materials like
      lignins, quinonic compounds and aromatics also exhibit strong absorbance thus
      interfering with the estimation when present in the media. The present study
      reports the lignin peroxidase production by some white rot fungi under different
      nutritional conditions. The veratryl alcohol oxidation assay procedure for lignin
      peroxidase has been compared with another method based on the oxidation of the
      dye azure B involving absorbance measurements in the visible range. The latter
      method proved to be much more advantageous over the veratryl alcohol oxidation
      method, in media supplemented with malt extract, lignin preparations and
      agricultural residues. The enzyme production by veratryl alcohol assay could be
      detected only in mineral salts broth. By the azure B assay the enzyme activity
      was detected in all the media tested. The supplements gave varied response in
      different media. Veratryl alcohol enhanced the enzyme production in malt extract
      broth and mineral salts malt extract broth. Among the lignin preparations Indulin
      AT increased the lignin peroxidase titres from 2 to 20 fold in different fungi.
      Similarly, wheat straw supplemented in mineral salts broth and malt extract
      broth, separately, strongly stimulated the lignin peroxidase production. The
      above studies revealed that azure B assay may act as a substitute or equivalent
      method.

PMID- 11339942
TI  - Thermostable, alkalophilic and cellulase free xylanase production by
      Thermoactinomyces thalophilus subgroup C.
AB  - Thermoactinomyces thalophilus produced cellulase free extracellular endo-1,4-beta
      xylanase (EC 3.2.1.8) at 50 degrees C and pH 8.5. Maximum xylanase production was
      achieved in fermentation medium using birchwood xylan as substrate after 96 h of
      growth at 50 degrees C. Other agricultural substrates such as wheat bran, wheat
      straw, sugarcane bagasse and cornstover produced less xylanase. The crude enzyme
      preparation from mutant T. thalophilus P2 grown under optimised fermentation
      conditions showed no cellulase contamination and maximum xylanase activity of 42
      U/ml at 65%deg;C and pH 8.5-9.0. This enzyme with initial xylanase activity of 42
      U/ml was found thermostable up to 65 degrees C and retaining 50% of its activity
      after its incubation for 125 min at 65 degrees C.

PMID- 11339943
TI  - Solvent-free enzymatic synthesis of alitame precursor using eutectic substrate
      mixtures.
AB  - N-benzyloxycarbonyl-L-aspartic acid ethyl ester-D-alanine amide, a derivative of
      alitame, was synthesized from a eutectic mixture of the substrates N
      benzyloxycarbonyl-L-aspartic acid diethyl ester and D-alanine amide using alpha
      chymotrypsin. The hydrophilic solvents DMSO and MEA were found to be the best
      adjuvants for formation of a eutectic substrate mixture. A low eutectic
      temperature of 27 degrees C was obtained for the substrate mixture containing 9%
      DMSO, 18% MEA, and 12% water. Under these conditions a conversion yield of 70.3%
      (mol/mol) was obtained at 37 degrees C. The optimum molar ratio of the acyl
      acceptor D-alanine amide and the acyl donor N-benzyloxycarbonyl-L-aspartic acid
      diethyl ester was 1:1.

PMID- 11339944
TI  - Purification and characterization of a novel bromoperoxidase-catalase isolated
      from bacteria found in recycled pulp white water.
AB  - A bacterial strain, Pseudomonad EF group 70B, containing a high catalase-like
      activity was found in process water (white water) from pulp using recycled
      fibers. The enzyme was purified and characterized, and found to be a
      hydroperoxidase. The active enzyme has an apparent molecular mass of about 153
      kDa with two identical subunits and a pI value of 4.7. It has a rather sharp pH
      optimum for catalase activity at 6.0 but exhibits catalase, peroxidase and
      brominating activities over a broad pH range from 4 to 8. It was not inhibited by
      3-amino-1,2,4-triazole. Peroxidase-like activity was found when adding o
      dianisidine, pyrogallol, guaiacol and 4-aminoantipyrine. Brominating activity was
      noticed using monochlorodimedone as a substrate. The absorption spectrum
      exhibited a Soret band at 404 nm. Upon reduction with dithionite the Soret peak
      decreased and shifted to 436 nm. Pyridine hemochrome spectra indicated the
      presence of a protophorfyrin IX heme group and the enzyme was inhibited by the
      known heme ligands cyanide and azide. N-terminal amino acid analysis gave the
      sequence STEVKLPYAVAGGGTTILDAFPGE, which showed no homology with those of known
      catalases or peroxidases. It is concluded that the enzyme is a novel type of
      catalase-peroxidase or, more specifically, a bromoperoxidase-catalase, and that
      future developments of inhibitors of hydrogen peroxide-degrading activities in
      white water may be based on this enzyme and other catalase-peroxidases.

PMID- 11339945
TI  - The potential application of aqueous two-phase systems for in situ recovery of 6
      pentyl-infinity-pyrone produced by Trichoderma harzianum.
AB  - Commercial production of aroma compounds by de novo microbial biosynthesis has
      been principally limited by the low productivity so far achieved. Production of 6
      pentyl-alpha-pyrone (6PP), a coconut-like aroma compound, by Trichoderma
      harzianum has been limited by the toxic effect that occurs even at low
      concentration (<100 ppm). This work evaluated the feasibility of the use of
      aqueous-two phase systems (ATPS), as in situ extraction systems, in order to
      overcome the toxic effects of 6PP and to improve culture productivity. The
      partition behaviour of 6-pentyl-alpha-pyrone and Trichoderma harzianum mycelium
      in polyethylene glycol (PEG)-salt and PEG-dextran two-phase systems was
      investigated and it is reported for the first time. The evaluation of system
      parameters such as PEG molecular mass, concentration of PEG as well as salt,
      volume ratio (Vr) and dextran molecular mass, was carried out to determine under
      which conditions the 6PP partitions to the opposite phase that mycelium does. PEG
      dextran systems proved to be unsuitable for the in situ recovery of 6PP because
      either 6PP and biomass partitioned to the same phase or a large extraction phase
      was required for the process. ATPS extraction comprising Vr = 0.26, PEG 1450
      (7.2% w/w) and sulphate (16.6% w/w) provided the best conditions for the maximum
      accumulation of the biomass into the bottom phase and concentrated the 6PP in the
      opposite phase (i.e. 86% of biomass and 56% of 6PP of the total amount loaded
      from the fermentation extract into the ATPS) for ex situ bioseparation. However,
      this system caused complete inhibition of the growth of the microorganism during
      the in situ bioseparation, probably as a consequence of the high ionic strength
      resulting from the salt concentration. Consequently, two ATPS PEG 8000-sulphate
      (12%/7% and 6%/14%) were evaluated and proved to be more suitable in the
      potential application for the in situ recovery of 6PP.

PMID- 11339946
TI  - Biochemical approaches to the synthesis of ethyl 5-(s)-hydroxyhexanoate and 5-(s)
      hydroxyhexanenitrile.
AB  - Three different biochemical approaches were used for the synthesis of ethyl 5-(S)
      hydroxyhexanoate 1 and 5-(S)-hydroxyhexanenitrile 2. In the first approach, ethyl
      5-oxo-hexanoate 3 and 5-oxo-hexanenitrile 4 were reduced by Pichia methanolica
      (SC 16116) to the corresponding (S)-alcohols, ethyl (S)-5-hydroxyhexanoate 1 and
      5-(S)-hydroxyhexanenitrile 2, with an 80-90% yield and >95% enantiomeric excess
      (e.e). In the second approach, racemic 5-hydroxyhexanenitrile 5 was resolved by
      enzymatic succinylation, leading to the formation of (R)-5-hydroxyhexanenitrile
      hemisuccinate and leaving the desired alcohol 5-(S)-hydroxyhexanenitrile 2 with a
      yield of 34% (50% maximum yield) and >99% e.e. In the third approach, enzymatic
      hydrolysis of racemic 5-acetoxy hexanenitrile 6 resulted in the hydrolysis of the
      R-isomer to provide 5-(R)-hydroxyhexanenitrile, leaving 5-(S)
      acetoxyhexanenitrile 7 with a 42% yield (50% maximum yield) and >99% e.e.

PMID- 11339947
TI  - Oxygen monitoring in supercritical carbon dioxide using a fibre optic sensor.
AB  - Investigations of enzymatic reactions in supercritical CO(2) are often hindered
      by the high pressure involved in these processes, making reaction monitoring
      extremely difficult. This paper describes the implementation of a fiber optic
      based oxygen sensor into a high pressure reactor for supercritical carbon
      dioxide. The sensor is pressure resistant, working in supercritical carbon
      dioxide and reusable after depressurisation. The sensor signal is found to be
      affected by pressure changes, but stable at constant pressure. Oxygen
      concentration in supercritical CO(2) is monitored using the disproportionation of
      hydrogen peroxide as a simple oxygen producing reaction.

PMID- 11339948
TI  - Hydrolysis of whey proteins by proteases extracted from Cynara cardunculus and
      immobilized onto highly activated supports.
AB  - Blends of cardosins A and B, enzymes present in aqueous extracts of the flowers
      of the thistle (Cynara cardunculus L.), have for long been used as rennets by the
      cheesemaking industry in the Iberian Peninsula. These dimeric proteases are
      present in the stigmae and stylets of said flowers, and are thought to play a
      role in sexual reproduction of the plant. In the present research effort,
      production of cardosin derivatives (starting from a crude extract), encompassing
      full stabilization of their dimeric structure, has been attempted via covalent,
      multi-subunit immobilization onto highly activated agarose-glutaraldehyde
      supports. Boiling such enzyme derivatives in the presence of sodium dodecyl
      sulfate and beta-mercaptoethanol did not lead to leaching of enzyme, thus proving
      the effectiveness of the attachment procedure. Furthermore, derivatives prepared
      under optimal conditions presented ca. half the specific activity of the enzyme
      in soluble form, and were successfully employed at lab-scale trials to perform
      (selective) hydrolysis of alpha-lactalbumin, one of the major proteins in bovine
      whey.

PMID- 11339949
TI  - The enantioselective hydrolysis of 3-hydroxy-5-phenyl-4-pentenoicacidethylester
      in supercritical carbon dioxide using lipases.
AB  - A new experimental high-pressure-unit was constructed for the enantioselective
      enzymatic hydrolysis of 3-hydroxy-5-phenyl-4-pentenoicacidethylester (a precursor
      for biological interesting substances) in a biphasic buffer/SCCO(2)-system. One
      objective is to take advantage of the solubility differences of the substrate and
      the produced acid. Thus the different solubilities of the substrates and the
      products in the different phases were studied regarding to an overall process
      integration. One ester enantiomer is preferably hydrolyzed, the other remains in
      the supercritical phase. And the produced acid enantiomer is concentrated in the
      buffer phase. The decrease in pressure is followed by an extraction process of
      the remaining substrate-enantiomer, in consequence it will be possible to combine
      an enzymatic reaction with a separation step. The catalysis was optimized in
      regard to enantioselectivity, enantiomeric excess, conversion and reaction time.
      A high enantioselectivity is achieved for the aromatic substrate using the lipase
      of Pseudomonas cepacia. The results show that this unconventional reaction system
      offers tremendous advantages for enzyme process development.

PMID- 11339950
TI  - Salt inhibition kinetics in nitrification of synthetic saline wastewater.
AB  - Nitrification kinetics of synthetic saline wastewater was investigated by using
      an activated sludge unit. Initial experiments were performed with salt-free
      wastewater to obtain baseline information. Experiments with 3% salt concentration
      were performed at different sludge ages in order to investigate the system
      performance and salt inhibition effects on kinetic constants. Minimum sludge age
      required for complete nitrification increased from 12 days for salt-free
      wastewater to 25 days for 3% salt content. Salt inhibition was non-competitive
      type affecting both the maximum rate and the saturation constants. Inhibition
      constants were determined by using the experimental data as K(T1) = 200 g/liter
      and K(T2) = 7.4 g/liter. Further experiments were performed with salt
      concentrations between 0-5% to quantify variation of the rate and extent of COD
      removal with salt concentration. The rate and extent of nitrification decreased
      approximately 20% with 5% salt as compared to salt-free wastewater.

PMID- 11339951
TI  - Selection of fungal elicitors to increase indole alkaloid accumulation in
      catharanthus roseus suspension cell culture.
AB  - Various fungal elicitors derived from 12 fungi were tested to improve indole
      alkaloid production in Catharanthus roseus cell suspension cultures. Results show
      that different fungal mycelium homogenates stimulate different kinds of indole
      alkaloid (ajmalicine, serpentine and catharanthine) accumulation, which ranged
      from 2- to 5-fold higher than the control. Some fungal culture filtrates also
      efficiently elicited the biosynthesis of different indole alkaloids. The optimal
      elicitor addition and exposure time for the maximal alkaloid production were on
      day 7 after subculture and for 3 days of treatment but different fungal elicitors
      showed the different optimal treatment dosages. Additions of elicitor at the
      doses ranging from 5 mg/l to 30 mg/l of carbon hydrate equivalent resulted in
      varieous amounts and kinds of indole alkaloid accumulation. Exposed to a same
      fungal elicitor, several different cell lines generated the different responses
      regarding as growth rate, culture color and alkaloid production.

PMID- 11339952
TI  - Enhanced catharanthine production in catharanthus roseus cell cultures by
      combined elicitor treatment in shake flasks and bioreactors.
AB  - Chemical and fungal elicitors were added to Catharanthus roseus cell suspension
      cultures so as to improve the production of indole alkaloids. A synergistic
      effect on alkaloid accumulation was observed in C. roseus cell cultures when
      treated with some combined elicitors of fungal preparations and chemicals. Among
      them, the combination of tetramethyl amminium bromide and Aspergillum niger
      mycelial homogenate gave the highest ajmalicine yield (63 mg l(-1)) and an
      improved catharanthine accumulation (17 mg l(-1)). The combined elicitors of
      malate and sodium alginate resulted in the highest catharanthine yield (26 mg l(
      1)) and a high ajmalicine accumulation (41 mg l(-1)) in the cell cultures. Based
      on the synergistic effect of malate and sodium alginate, a process with enhanced
      catharanthine production in Catharanthus roseus cell cultures was developed in
      shake flasks and a bioreactor. After 10 days of culture, 25 mg l(-1), 32 mg l(-1)
      and 22 mg l(-1) catharanthine yield were obtained in 500-ml flasks, 1000-ml
      flasks and in a 20-l airlift bioreactor, respectively. Upon malate-alginate
      combining treatments, peroxidase, catalase and superoxide dismutase activities
      decreased in elicited cells but phenylalanine ammonia lyase and lipoxygenase
      activities increased dramatically. That suggests a typical defense responses took
      place in the combined elicitors-treated cell cultures. Furthermore, the combined
      elicitors also caused a significant increase of malondialdehyde level in cell
      cultures, which suggests a serious lipid peroxidation occurred in the elicited
      cell cultures. Comparison of these results suggests that malate and alginate
      combining treatment also stimulates defense responses, such as lipid
      peroxidation, in all C. roseus culture processes and this may mediate the indole
      alkaloid production via jasmonate pathway.

PMID- 11339953
TI  - Purification and some characteristics of a recombinant dimeric rhizobium meliloti
      beta-galactosidase expressed in escherichia coli.
AB  - A recombinant Rhizobium meliloti beta-galactosidase was purified to homogeneity
      from an Escherichia coli expression system. The gene for the enzyme was cloned
      into a pKK223-3 plasmid which was then used to transform E. coli JM109 cells. The
      enzyme was purified 35-fold with a yield of 34% by a combination of DEAE
      cellulose (pH 8.0) and two sequential Mono Q steps (at pH 8.0 and 6.0,
      respectively). The purified enzyme had an apparent molecular mass of 174 kDa and
      a subunit molecular weight of 88 kDa, indicating that it is a dimer. It was
      active with both synthetic substrates p-nitrophenyl beta-D-galactopyranoside
      (PNPG) and o-nitrophenyl beta-D-galactopyranoside (ONPG) with K(m)(PNPG) and
      K(m)(ONPG) of 1 mM at 25 degrees C. The k(cat)/K(m) ratios for both substrates
      were approximately 70 mM(-1) sec(-1), indicating no clear preference for either
      PNPG or ONPG, unlike E. coli beta-galactosidase. After non-denaturing
      electrophoresis, active beta-galactosidase bands were identified using 5-bromo-4
      chloro-3-indolyl beta-D-galactopyranoside (X-gal) or 6-bromo-2-naphthyl beta-D
      galactopyranoside (BNG) and diazo blue B.

PMID- 11339954
TI  - Submerged cultivation of scytalidium thermophilum on complex lignocellulosic
      biomass for endoglucanase production.
AB  - Scytalidium thermophilum endoglucanase production was analyzed on lignocellulosic
      biomass in submerged cultures at 45 degrees C and 155 rpm for 8 days.
      Endoglucanase, adsorbability of endoglucanase onto avicel, as well as
      exoglucanase, and filter paper activities were determined and compared with those
      on microcrystalline cellulose (avicel) as the main source of carbon. Lentil bran
      and sunflower seed bagasse yielded c. 1.5 fold more endoglucanase and avicel
      adsorbable endoglucanase activity than avicel, and activities on grass clippings
      were similar. Grass clippings yielded the highest percentage of avicel-adsorbable
      endoglucanase among all lignocellulosic substrates tested. By the time when
      endoglucanase activities reached maximal levels, exoglucanase activities on
      lentil bran, sunflower seed bagasse and grass clippings were c. 1.5-3 fold lower
      than those on avicel, although a significant difference in filter paper
      activities was not observed. On lignocellulosic biomass, maximum levels of
      endoglucanase activity were reached within 3-4 days, and within 6-7 days on
      avicel.

PMID- 11339955
TI  - Coimmobilization of L-asparaginase and glutamate dehydrogenase onto highly
      activated supports.
AB  - In the present research work, production of coimmobilized derivatives of L
      asparaginase and glutamate dehydrogenase was attempted. Comparison of
      immobilization of each enzyme independently with coimmobilization of the two
      enzymes unfolded important advantages of the latter, namely a decrease in the
      induction period (time before the maximum reaction rate is virtually achieved)
      and an increase in the maximum reaction rate. The effectiveness of the
      independent enzyme derivatives was low; however, it was enhanced by three-fold
      when the enzymes were coimmobilized onto the same agarose-glutaraldehyde support.
      Each supporting agarose bead may in fact be viewed as a nano-reactor with in situ
      reaction and separation (i.e. elimination of the ammonia formed), with the
      nanoenvironment surrounding each enzyme molecule being essentially devoid of
      steric hindrance.

PMID- 11339956
TI  - Over-expression and properties of a purified recombinant Bacillus licheniformis
      lipase: a comparative report on Bacillus lipases.
AB  - The gene coding for an extracellular lipase of Bacillus licheniformis was cloned
      using PCR techniques. The sequence corresponding to the mature lipase was
      subcloned into the pET 20b(+) expression vector to construct a recombinant lipase
      protein containing 6 histidine residues at the C-terminal. High-level expression
      of the lipase by Escherichia coli cells harbouring the lipase gene-containing
      expression vector was observed upon induction with IPTG at 30 degrees C. A one
      step purification of the recombinant lipase was achieved with Ni-NTA resin. The
      specific activity of the purified enzyme was 130 units/mg with p-nitrophenyl
      palmitate as substrate. The enzyme showed maximum activity at pH 10-11.5 and was
      remarkably stable at alkaline pH values up to 12. The enzyme was active toward p
      nitrophenyl esters of short to long chains fatty acids but with a marked
      preference for esters with C(6) and C(8) acyl groups. The amino acid sequence of
      the lipase shows striking similarities to lipases from Bacillus subtilis and
      Bacillus pumilus. Based on the amino acid identity and biochemical
      characteristics, we propose that Bacillus lipases be classified into two distinct
      subfamilies of their own.

PMID- 11339957
TI  - Optimization of the immobilization parameters and operational stability of
      immobilized hydantoinase and l-N-carbamoylase from Arthrobacter aurescens for the
      production of optically pure l-amino acids.
AB  - 2The immobilization parameters were optimized for the hydantoinase and the L-N
      carbamoylase from Arthrobacter aurescens DSM 3747 or 3745, respectively. To
      optimize activity yields and specific activities for the immobilization to
      Eupergit C, Eupergit C 250 L, and EAH-Sepharose wild-type, recombinant and
      genetically modified ('tagged') enzymes were investigated concerning the
      influence of the protein concentration, the kind of support and the
      immobilization method. For both enzymes, the use of the recombinant proteins
      resulted in enhanced specific activities especially when using a hydrophilic
      support for immobilization such as Sepharose. In the case of a genetically
      modified hydantoinase carrying a His(6)-tag, affinity coupling led to a loss of
      activity of higher than 80%. Both enzymes were significantly stabilized by
      immobilization: In packed bed reactors, Eupergit C 250 L (NH(2))-immobilized
      hydantoinase and EAH-Sepharose-immobilized L-N-carbamoylase showed half-life
      times of approx. 14000 and 900 hours, respectively. Together with specific
      activities of the immobilized enzymes of 2.5 U/g wet carrier (hydantoinase) and
      10 U/g wet carrier (L-N-carbamoylase) the newly developed biocatalysts are
      sufficient to fulfill industrial requirements.In comparison to the free enzymes,
      temperature and pH-optima were increased by 10 degrees C and one pH unit,
      respectively, after immobilization. The pH and temperature optima of the
      hydantoinase (L-N-carbamoylase) were determined to be pH 8.5-10 (pH 9.5) and 45
      60 degrees C (60 degrees C).In order to provide sufficient amounts of biocatalyst
      for the process development in mini plant scale, a 50 fold scale-up of the
      optimized immobilization procedure was carried out for both enzymes. Because of
      the overlapping optima, both immobilized enzymes can be operated together in one
      reactor.

PMID- 11339958
TI  - Reverse transcription of inserted DNA in a monkey gives us ANDi.
AB  - The recent report of the birth of the first transgenic primate, ANDi, marks an
      important next stage in the progressive development of novel gene therapy
      strategies for understanding and treating human genetic disease. The
      opportunities and benefits offered by this technology are significant but must be
      carefully balanced against the particular practical, ethical and financial costs
      involving the use of primates in experimental medicine.

PMID- 11339959
TI  - Reverse transcription of inserted DNA in a monkey gives us ANDi: response from
      Chan et al.

PMID- 11339960
TI  - Hang onto your haem...what's happened to CYP4A?

PMID- 11339961
TI  - iNOS in arthritis--inducible or innocent?

PMID- 11339962
TI  - Antinociceptive and pro-inflammatory roles for NPY Y(1) receptors.

PMID- 11339963
TI  - Animal experiments in the political arena.

PMID- 11339964
TI  - Heparin and cancer revisited.

PMID- 11339965
TI  - Tailored treatments.

PMID- 11339966
TI  - Disappointment for Parkinson's disease patients.

PMID- 11339967
TI  - Patients and patents.

PMID- 11339968
TI  - Conference fast-tracking.

PMID- 11339969
TI  - Clone database unveiled.

PMID- 11339970
TI  - A nicotine fix on the NHS.

PMID- 11339971
TI  - Doing what comes "naturally".

PMID- 11339972
TI  - How does pindolol improve antidepressant action?
AB  - Since 1994, the beta-adrenoceptor and 5-HT(1A/1B) receptor ligand pindolol has
      been used to accelerate or enhance the clinical effects of antidepressant drugs,
      such as the selective 5-HT reuptake inhibitors (SSRIs), that act primarily on 5
      HT-containing neurones. Pindolol was initially thought to act by preventing the
      inhibition of 5-HT release, elicited by SSRIs and other 5-HT-acting drugs, as a
      result of its ability to antagonize the action of 5-HT at midbrain raphe 5-HT(1A)
      autoreceptors that control the activity of ascending 5-HT-mediated pathways.
      However, the partial agonist properties of pindolol at 5-HT(1A) receptors and
      beta-adrenoceptors suggest that other explanations for its action are also
      possible. In this article, recent controversial data on the mechanism of action
      of pindolol, which are crucial for the development of more rapid and efficient
      antidepressant therapies, will be discussed.

PMID- 11339973
TI  - Role of 5-HT(2C) receptors in the control of central dopamine function.
AB  - Substantial evidence suggests that the functional status of the mesocorticolimbic
      dopamine (DA) system originating in the ventral tegmental area is under a phasic
      and tonic inhibitory control by the 5-HT system that acts by stimulating 5-HT(2C)
      receptor subtypes. Indeed, electrophysiological and biochemical data demonstrate
      that 5-HT(2C) receptor agonists decrease, whereas 5-HT(2C) receptor antagonists
      enhance, mesocorticolimbic DA function. However, 5-HT(2C) receptors do not appear
      to play a relevant role in the control of the nigrostriatal DA system originating
      in the substantia nigra pars compacta. In this article, the role of 5-HT(2C)
      receptors in the control of brain DA function will be reviewed, and the search
      for new therapies for neuropsychiatric disorders, such as depression,
      schizophrenia and drug addiction, based on these findings will be discussed.

PMID- 11339974
TI  - Therapeutic modulation of transcription factor activity.
AB  - Aberrant gene expression is a fundamental cause of many disease-associated
      pathophysiologies. The pharmacological modulation of transcription factor
      activity therefore represents an attractive therapeutic approach to such
      disorders. With the exception of nuclear receptors, which are the direct targets
      of pharmaceuticals, other known classes of transcription factors are largely
      regulated indirectly by drugs that impact upon those signal transduction cascades
      that alter transcription factor phosphorylation and dephosphorylation and/or
      nuclear import. However, recent advances in drug discovery technologies now
      enable high-throughput screens that can identify molecules that act directly at
      the level of transcription factor complexes.

PMID- 11339975
TI  - HERG K+ channels: friend and foe.
AB  - The K+ channel encoded by the human ether-a-go-go related gene (HERG) is one of
      many ion channels that are crucial for normal action potential repolarization in
      cardiac myocytes. HERG encodes the pore-forming subunit of the rapid component of
      the delayed rectifier K+ channel, I(K(Vr)). HERG K+ channels are of considerable
      pharmaceutical interest as possible therapeutic targets for anti-arrhythmic
      agents and as the molecular target responsible for the cardiac toxicity of a wide
      range of pharmaceutical agents. Recent studies of the molecular basis of the
      promiscuity of HERG K+ channel drug binding has not only started to shed light on
      this tricky pharmaceutical problem but has also provided further insights into
      the structure and function of HERG K+ channels.

PMID- 11339976
TI  - Pharmacotherapy of obesity: targets and perspectives.
AB  - The search for anti-obesity agents has become one of the most exciting areas in
      drug discovery. Subsequent to an enormous increase in the number of possible
      molecular targets, the focus has shifted from target identification to target
      validation. Because important biological functions such as the regulation of
      energy intake and expenditure are controlled by complex systems, an improved
      understanding of pathophysiology is a prerequisite for the selection of
      successful development candidates for the treatment of obesity. Although most of
      the information on the regulation of energy balance has been obtained from
      rodents, various monogenic forms of human obesity provide clinical proof of
      concept for some of these mechanisms. However, it is still not known which are
      the most promising clinical approaches to lowering body weight and subsequently
      reducing morbidity and mortality.

PMID- 11339977
TI  - Cardiac mechanotransduction: from sensing to disease and treatment.
AB  - In heart muscle a mechanical stimulus is sensed and transformed into adaptive
      changes in cardiac function by a process called mechanotransduction. Adaptation
      of heart muscle to mechanical load consists of neurohumoral activation and
      growth, both of which decrease the initial load. Under prolonged overload this
      process becomes maladaptive, leading to the development of left ventricular
      hypertrophy and ultimately to heart failure. Widespread synergism and crosstalk
      among a variety of molecules and signals involved in hypertrophic signaling
      pathways make the prevention or treatment of left ventricular hypertrophy and
      heart failure a challenging task. Therapeutic strategies should include either a
      complete and continuous reduction of load or normalization of left ventricular
      mass by interventions aimed at specific targets involved in mechanotransduction.

PMID- 11339978
TI  - An integrated approach for genome-wide gene expression analysis.
AB  - Since efficient and relatively cheap methods were developed for determining
      biosequences, a lot of biosequence data has been generated. As the main problem
      in molecular biology is the analysis of the data instead of the data acquisition,
      part of the study of computational biology is to extract all kinds of meaningful
      information from the sequences. Computer-assisted methods have become very
      important in analyzing biosequence data. However, most of the current computer
      assisted methods are limited to finding motifs. Genes can be regulated in many
      ways, including combinations of regulatory elements. This research is aimed at
      developing a new integrated system for genome-wide gene expression analysis. This
      research begins with a new motif-finding method, using a new objective function
      combining multiple well defined components and an improved stochastic iterative
      sampling strategy. Combinatorial motif analysis is accomplished by constructive
      induction that analyzes potential motif combinations. We then apply standard
      inductive learning algorithms to generate hypotheses for different gene
      behaviors. A genome-wide gene expression analysis demonstrated the value of this
      novel integrated system.

PMID- 11339979
TI  - Border-tracing algorithm implementation for the femoral geometry reconstruction.
AB  - In some orthopaedic applications such as the design of custom-made hip
      prostheses, reconstruction of the bone morphology is a fundamental step.
      Different methods are available to extract the geometry of the femoral medullary
      canal from computed tomography (CT) images. In this research, an automatic
      procedure (border-tracing method) for the extraction of bone contours was
      implemented and validated. A composite replica of the human femur was scanned and
      the CT images processed using three different methods, a manual procedure; the
      border-tracing algorithm; and a threshold-based method. The resulting contours
      were used to estimate the accuracy of the implemented procedure. The two software
      techniques were more accurate than the manual procedure. Then, these two
      procedures were applied to an in vivo CT data set in order to determine to most
      critical region for repeatability. Only for the images located in this region,
      the repeatability measurement was carried out for six in vivo CT data sets to
      evaluate the inter-femur repeatability. The border-tracing method was found to
      achieve the highest repeatability.

PMID- 11339980
TI  - A SAS macro for sample size re-estimation.
AB  - The assessment of sample size in clinical trials comparing means requires a
      variance estimate of the main efficacy variable. If no reliable information about
      the variance of the key response is available at the beginning of a clinical
      trial, the use of data from the first 'few' patients entered in the trial
      ('internal pilot') may be appropriate to estimate the variance and thus to
      recalculate the required sample size. A SAS macro that implements the EM
      algorithm for carrying out and simulating such interim power evaluations without
      unblinding the treatment status is presented.

PMID- 11339981
TI  - A step-by-step guide to non-linear regression analysis of experimental data using
      a Microsoft Excel spreadsheet.
AB  - The objective of this present study was to introduce a simple, easily understood
      method for carrying out non-linear regression analysis based on user input
      functions. While it is relatively straightforward to fit data with simple
      functions such as linear or logarithmic functions, fitting data with more
      complicated non-linear functions is more difficult. Commercial specialist
      programmes are available that will carry out this analysis, but these programmes
      are expensive and are not intuitive to learn. An alternative method described
      here is to use the SOLVER function of the ubiquitous spreadsheet programme
      Microsoft Excel, which employs an iterative least squares fitting routine to
      produce the optimal goodness of fit between data and function. The intent of this
      paper is to lead the reader through an easily understood step-by-step guide to
      implementing this method, which can be applied to any function in the form
      y=f(x), and is well suited to fast, reliable analysis of data in all fields of
      biology.

PMID- 11339982
TI  - Estimation of body fat from skinfold thickness.
AB  - The fat content of the human body has physiological and medical importance. It
      may influence morbidity and mortality, it may affect the ability to withstand
      exposure to cold and starvation, and it may alter the effectiveness of drugs and
      anaesthetics. It may also be the cause of reduced insulin sensitivity in some
      population groups. Thus, the measurement of the total body fat provides useful
      information. A computer program, written in quick basic language, was developed,
      to compute the equivalent fat content, as a percentage of body-weight, for a
      range of values for the sum of the four skinfolds, of Egyptian males and females
      of different ages. This is based on a table developed by Durnin and Womersley.
      The computer program was run using skinfolds of Egyptian males and females of
      different ages. Satisfactory results were obtained. This program can be used to
      calculate the total body fat with relative ease and reasonable accuracy. This
      should make it of common use in many fields of medicine, physiology, nutrition
      and anthropology, particularly in population studies comprising a large number of
      subjects.

PMID- 11339983
TI  - Standardization of non-aggregated data: theory and practice.
AB  - Direct standardization of rates is a classical method in epidemiology by which
      the relationship between confounders and variables of analysis is balanced
      between the samples or populations to be compared. While the method is
      appropriate if single variables of aggregated data sets are to be compared, it is
      limited with respect to handling many variables of different measurement scale,
      especially in primary data situations. Therefore the method of direct
      standardization is adapted to the analysis of non-aggregated data. Computation of
      not only rates but other statistics of central tendency and dispersion as well as
      confidence intervals hence becomes feasible. In addition it is possible to re
      adjust the primary data weights in order to perform stratified analyses. A
      procedure to do so, based solely on the available original weights without the
      need for analyzing the standard population is proposed along with an extensive
      SAS macro. The utility allows for the rapid and standardized analysis and
      tabulation of large multi-variable data sets. Both the statistical and technical
      properties of the macro are discussed and its usage is explained as well as
      exemplified.

PMID- 11339984
TI  - The role of coherence and cohesion in text comprehension: an event-related fMRI
      study.
AB  - Text processing requires inferences for establishing coherence between successive
      sentences. In neuropsychological studies and brain imaging studies, these
      coherence-building processes have been ascribed to the right hemisphere. On the
      other hand, there is evidence for prefrontal brain damage causing non-aphasic
      language disorders, in which text level processes are impaired. In this study, we
      used an event-related, whole-head fMRI methodology to evaluate the contributions
      of prefrontal areas and the right hemisphere to coherence building. We scanned 12
      participants while they read 120 sentence pairs and judged their coherence. Four
      conditions were used, resulting from crossing coherence and cohesion (i.e. the
      presence of a lexical connection). A behavioral pretest confirmed that cohesion
      aided establishing coherence, whereas it hindered the detection of coherence
      breaks. In the fMRI study, all language conditions yielded activation in left
      frontolateral and temporolateral regions, when compared to a physical control
      task. The differences due to coherence of the sentence pairs were most evident in
      larger activation for coherent as compared to incoherent sentence pairs in the
      left frontomedian wall, but also in posterior cingulate and precuneal regions.
      Finally, a left inferior prefrontal area was sensitive to the difficulty of the
      task, and in particular to the increase in processing costs when cohesion falsely
      indicated coherence. These results could not provide evidence for a special
      involvement of the right hemisphere during inferencing. Rather, they suggest that
      the left frontomedian cortex plays an important role in coherence building.

PMID- 11339985
TI  - Automaticity and attention: investigating automatic processing in texture
      segmentation with event-related brain potentials.
AB  - The present article deals with the question of automaticity and/or plasticity of
      processes in early vision. The detection of irregularities in an otherwise
      homogeneous surrounding, as studied in texture segmentation tasks, is considered
      an example of an automatic process in the processing of visual information.
      Participants in texture segmentation experiments are usually instructed to
      respond to the texture stimuli, i.e. attention is completely allocated towards
      them. Automaticity, however, would imply that processing takes also place when no
      attention is allocated to the texture stimuli and participants, e.g. perform
      another primary task. We investigated the automaticity of texture segmentation by
      recording Event-related potentials which allow to investigate processing also
      when no overt response is given. Three experiments investigated the role of
      attention in texture segmentation by varying task relevance of the texture
      stimuli. Participants had to either discriminate homogeneous or inhomogeneous
      textures or had to perform a different primary task of varying complexity. Two
      components were found to be sensitive to texture segmentation, a posterior N2 and
      a positivity within the P3 time interval. Both components were also observed when
      texture segmentation was task-irrelevant. However, while the posterior N2 was not
      affected by the complexity of the primary task and thus showed some degree of
      automaticity, the P3 was found to be dependent on the attentional resources left
      over by the primary task.

PMID- 11339986
TI  - Neurophysiological signals of working memory in normal aging.
AB  - To examine how neurophysiological signals of working memory (WM) change with
      normal aging, we recorded EEGs from healthy groups (n=10 each) of young (mean
      age=21 years), middle-aged (mean=47 years), and older (mean=69 years) adults.
      EEGs were recorded while subjects performed easy and difficult versions of a
      spatial WM task. Groups were matched for IQ (mean=123; WAIS-R) and practiced in
      task performance. Responses slowed with age, particularly in the more difficult
      task. Advanced age was associated with decreased amplitude and increased latency
      of the parietal P300 component of the event-related potential and an increase in
      the amplitude of a frontal P200 component. Spectral features of the EEG also
      differed between groups. Younger subjects displayed an increase in the frontal
      midline &theta; rhythm with increased task difficulty, a result not observed in
      older subjects. Age-related changes were also observed in the task-related alpha
      signal, the amplitude of which decreases as more neurons become involved in task
      related processing. Young adults showed a decrease in alpha power with increased
      task difficulty over parietal regions but not over frontal regions. Middle-aged
      and older adults showed decreased alpha power with increased task difficulty over
      both frontal and parietal regions. This suggests that normal aging may be
      associated with changes in the fronto-parietal networks involved with spatial WM
      processes. Younger subjects appear to use a strategy that relies on parietal
      areas involved with spatial processing, whereas older subjects appear to use a
      strategy that relies more on frontal areas.

PMID- 11339987
TI  - Thalamic volume predicts performance on tests of cognitive speed and decreases in
      healthy aging. A magnetic resonance imaging-based volumetric analysis.
AB  - Recent studies have indicated a role for the thalamus in attention, arousal and
      the capacity to perform tasks of speeded information processing. The present
      study evaluated the role of the thalamus in age-related cognitive decline by
      investigating the correlations between thalamic volume, cognition and age. This
      was done in 57 healthy subjects ranging from 21 to 82 years of age. All subjects
      underwent neurocognitive testing with information processing tests and structural
      magnetic resonance imaging. A significant decrease in volume of the thalamus with
      increasing age was found, relatively stronger than and independent of the
      decrease of total brain volume. The decrease of thalamic volume was apparent
      before the onset of loss of volume of the total brain. Over the age-span studied,
      the thalamic decrease in volume correlated with the diminished performance on
      tests of cognitive speed. Additionally, in young and middle-aged, but not in old
      subjects, the size of the thalamus predicted performance on tasks that require
      cognitive speed.

PMID- 11339988
TI  - The effect of immediate and delayed word repetition on event-related potential in
      a continuous recognition task.
AB  - The dissociation of immediate and delayed word repetition was studied using a
      continuous recognition memory task and event-related potential (ERP). Among 240
      stimulus words, 40 words were not repeated, 100 were immediately repeated and 100
      were repeated after 5 intervening words. Words presented only once during the
      experiment were referred to as new words. Subjects responded faster and more
      accurately to words repeated immediately than to new words and to words repeated
      after a delay. In terms of ERP results, immediate repetition was associated with
      large P300 amplitude, early P300 latency and the absence of N400, while delayed
      repetition was associated with small P300 amplitude, late P300 latency and the
      presence of N400. N400 was elicited only to new words and to those repeated after
      intervening words. The general morphology of the waveforms was similar for two
      repetition conditions until around 310 ms after the onset of stimulus. These
      results indicate that distinct neural systems subserve the immediate and delayed
      repetition effect, and that the difference between the two emerges around 310 ms
      poststimulus. Immediate and delayed word repetition are considered in terms of
      template matching and memory searching, and are possibly mediated by the parietal
      and left medial temporal lobes, respectively.

PMID- 11339989
TI  - Semantic processing of open- and closed-class words: an event-related potentials
      study.
AB  - Previous research on open- and closed-class words has revealed the existence of
      several differences in the processing of these types of vocabulary. In this paper
      the processing of open- and closed-class words was compared by means of an early
      electrical brain response, recognition potential (RP), which indexes semantic
      processing and originates from basal extrastriate areas. The effects of word
      frequency on closed-class words were also investigated. For these purposes, open-
      and closed-class words, among other stimuli, were presented by means of the rapid
      stream stimulation procedure. Results showed that there were no significant
      differences when comparing the RP evoked by open- and closed-class words in the
      left hemisphere. However, in the right hemisphere this situation changed: the RP
      evoked by open- and closed-class words did differ. Moreover, there were no
      differences between the RP evoked by closed-class words and pseudowords. These
      patterns of results suggest that the semantic processing of closed-class words
      shares some aspects with the processing of open-class words, despite the
      existence of some differences. Thus, whereas the semantic processing of open
      class words recruits brain areas of both hemispheres, the semantic processing of
      closed-class words is left-lateralized. A second purpose of this work is to study
      word-frequency effects on closed-class words. Our results show the insensitivity
      of closed-class words to word-frequency effects.

PMID- 11339990
TI  - Active, passive and snapshot exploration in a virtual environment: influence on
      scene memory, reorientation and path memory.
AB  - We investigated the importance of active, passive and snapshot exploration on
      spatial memory in a virtual city. The exploration consisted in traveling along a
      series of streets. 'Active exploration' was performed by giving directions to the
      subject who controlled his displacement with a joystick. During 'passive'
      exploration, the travel was imposed by the computer. Finally, during 'snapshot
      exploration', simple views of the scene were presented sequentially every 4 m.
      Travel velocity was the same in all cases. The three visual exploration modes
      were compared with three spatial memory measures: (1) scene recognition, (2) at
      the end of the path, reorientation toward the departure point and (3) drawings of
      the path shape. Scene recognition and estimation of the direction of the starting
      point of the path were not affected by the mode of exploration. In contrast,
      reproduction of the shape of the path was affected: the errors of reproduction
      were greater for the snapshot exploration than for the other two conditions;
      there was no difference between the other two conditions. These results suggest
      that (1) 2D image features from a visual scene are memorized. Moreover, (2)
      pointing towards the origin of the path relies on motion duration integration or
      a frame of reference integrated during displacement. Finally, (3) drawing the
      path shape involves a deliberate reconstruction process.

PMID- 11339991
TI  - Fabrication of ultra-thin polypyrrole-glucose oxidase film from supporting
      electrolyte-free monomer solution for potentiometric biosensing of glucose.
AB  - A simple electropolymerisation process is described for the fabrication of an
      ultra-thin ( approximately 55 nm) polypyrrole (PPy)-glucose oxidase (GOD) film in
      a supporting electrolyte-free monomer solution for potentiometric biosensing of
      glucose. The optimum conditions for growing the ultra-thin film include 0.1 M
      pyrrole, 55-110 U/ml GOD, an applied current density of 0.05 mA/cm(2) and an
      electrical charge of 25 mC/cm(2). Long-term storage of the biosensor in acetate
      buffer improved the sensitivity of the biosensor by a factor of approximately
      two. The biosensor can also be used repeatedly for over 2 months with little or
      no loss in sensitivity. The interference effect of ascorbic acid was successfully
      reduced by inclusion of an outer PPy-Cl layer.

PMID- 11339992
TI  - Optical peroxide biosensor using the electrically controlled-release technique.
AB  - An optical biosensor using an electrically controlled-release system was
      developed for the measurement of peroxide concentration. The electrically
      controlled-release system consisted of a current-supplying system and a polymer
      complex by hydrogen bonding between the carboxylic and oxazoline group. The
      polymer complex was formed below pH 5.0 and was degraded above pH 5.4. The local
      pH change near the surface of the polymer complex could be controlled by applying
      the electric current to release an enzyme reaction reagent, 4-hydroxyphenylacetic
      acid (HPA), in the polymer complex. The releasing rate of HPA was proportional to
      the electric current applied to the polymer complex. The model of the controlled
      release system was proposed to predict the degradation velocity of the polymer
      complex, which is equivalent to the releasing rate of HPA. The released HPA and
      analyte, peroxide, flowed into the reactor with the immobilized enzyme and then
      reacted with the enzyme. The peroxide concentration was measured based on the
      fluorescence detection of enzyme reaction product, 6,6'-dihydroxy (1,1'-biphenyl)
      3,3'-diacetic acid (DBDA). The proposed biosensor had the linear analytical range
      of 0.025 approximately 1.0 mM with a response time of 20 min, good repeatability,
      and reproducibility.

PMID- 11339993
TI  - Mediatorless biosensor for H(2)O(2) based on recombinant forms of horseradish
      peroxidase directly adsorbed on polycrystalline gold.
AB  - Four forms of horseradish peroxidase (HRP) have been used to prepare peroxidase
      modified gold electrodes for mediatorless detection of peroxide: native HRP, wild
      type recombinant HRP, and two recombinant forms containing six-His tag at the C
      terminus and at the N-terminus, respectively. The adsorption of the enzyme
      molecules on gold was studied by direct mass measurements with electrochemical
      quartz crystal microbalance. All the forms of HRP formed a monolayer coverage of
      the enzyme on the gold surface. However, only gold electrodes with adsorbed
      recombinant HRP forms exhibited high and stable current response to H(2)O(2) due
      to its bioelectrocatalytic reduction based on direct electron transfer between
      gold and HRP. The sensitivity of the gold electrodes modified with recombinant
      HRPs was in the range of 1.4-1.5 A M(-1) cm(-2) at -50 mV versus Agmid R:AgCl.
      The response to H(2)O(2) in the concentration range 0.1-40 microM was not
      dependent on the presence of a mediator (i.e. catechol) giving strong evidence
      that the electrode currents are diffusion limited. Lower detection limit for
      H(2)O(2) detection was 10 nM at the electrodes modified with recombinant HRPs.

PMID- 11339994
TI  - An ultrafiltration catheter for monitoring of venous lactate and glucose around
      myocardial ischemia.
AB  - Early detection of myocardial ischemia is of major importance in critical-care
      medicine. Changes of lactate or glucose levels in the cardial venous efflux may
      be useful parameters. We succeeded in integrating an ultrafiltration membrane in
      a cardiac catheter for continuous sampling. The ultrafiltrate was analyzed
      outside the body, resulting in a lag-time of about 24 min. Biosensors in a flow
      injection analysis system were used for minute by minute sample analyses. The
      coronary sinus of pigs was catheterized to monitor the effects of 5, 15 or 45 min
      ischemia by coronary artery obstruction or myocardial stress by dobutamine
      infusion. A total of 27 h was monitored. The intravascular response time was
      1.33+/-0.61 min (10-90%). Linear regression in vivo of blood and ultrafiltrate
      samples was 0.977 for lactate and 0.994 for glucose. Lactate levels rose 0.38+/
      0.10 mM above baseline within 5 min after ischemia. Reperfusion was clearly
      marked by a promptly peaking lactate release (maximum 9.27 mM). Myocardial stress
      by dobutamine increased glucose but not lactate levels. Once, a wall effect was
      noted at the catheter tip. In vivo semi-continuous myocardial monitoring of
      absolute lactate and glucose concentrations was thus achieved by an
      ultrafiltration catheter. Ischemia and reperfusion can be detected very early by
      a lactate level rise. Further, development of the ultrafiltration catheter will
      be focused on the diagnostic potential of lactate monitoring for patients.

PMID- 11339995
TI  - Diagnosing acute liver graft rejection: experimental application of an
      implantable telemetric impedance device in native and transplanted porcine
      livers.
AB  - BACKGROUND AND AIMS: Diagnosis of acute rejection is a complex and persistent
      problem in liver transplantation. Focused on the use of proprietary impedance
      technology a porcine liver model was designed to provide immediate information
      for differentiation of normal and acute rejecting tissue by an implantable
      telemetric device. METHODS: Electrical impedance was analyzed by electrodes
      implanted in vitro and in vivo in the liver of pigs, where impedance is derived
      from measurements of voltage transients produced in response to programmed
      current pulses. Consequent electric recordings in porcine livers after
      transplantation and after mere laparotomy were evaluated in relation to
      biochemical parameters and histological results of liver biopsies. RESULTS: Acute
      rejection was correctly predicted in all cases and correctly excluded in the
      remaining 32 biopsy related impedance recordings (P<0.004). Impedance
      measurements not only correlated with the diagnosis from liver biopsy specimen
      (r=0.84, P<0.0001) but also exemplified the severity of histological acute
      rejection. CONCLUSION: Impedance analysis reveals evident physiologic relation of
      acute liver graft rejection and electrical organ properties. Electrodes implanted
      in transplanted porcine livers allow running less invasive monitoring and thus
      early detection of rejection. The technology may have broad value in providing an
      immediate diagnosis of acute rejection, reducing unnecessary patient anxiety and
      eliminating the significant expenses associated with multiple referrals,
      expensive sample handling and tissue analysis.

PMID- 11339996
TI  - Capacitive detection of glucose using molecularly imprinted polymers.
AB  - A novel glucose biosensor based on capacitive detection has been developed using
      molecularly imprinted polymers. The sensitive layer was prepared by
      electropolymerization of o-phenylenediamine on a gold electrode in the presence
      of the template (glucose). Cyclic voltammetry and capacitive measurements
      monitored the process of electropolymerization. Surface uncovered areas were
      plugged with 1-dodecanethiol to make the layer dense, and the insulating
      properties of the layer were studied in the presence of redox couples. The
      template molecules and the nonbound thiol were removed from the modified
      electrode surface by washing with distilled water. A capacitance decrease could
      be obtained after injection of glucose. The electrode constructed similarly but
      with ascorbic acid or fructose only showed a small response compared with
      glucose. The stability and reproducibility of the biosensor were also
      investigated.

PMID- 11339997
TI  - A laminated, flex structure for electronic transport and hybridization of DNA.
AB  - We have developed the first prototypes of a three-dimensional,
      electrophoretically driven microlaboratory for the analysis of proteins and DNA.
      By selecting the appropriate spacing and geometrical configuration,
      oligonucleotides were transported, in a controlled, rapid fashion, by
      electrophoresis in free-space. Transport efficiencies over 2 mm distances
      exceeded 70%. Electrodes of similar design were combined with an electronically
      addressed DNA hybridization chip to form a fully electrophoretic microlaboratory.
      In this instance, gold-plated copper electrodes were patterned on a 2 mil thick
      polyimide substrate. This polyimide layer was stiffened with 20 mil of polyimide
      to provide support for flip-chip bonding of our standard 100-site Nanochip. This
      composite structure illustrated three-dimensional transport of target
      oligonucleotides, through a via in the polyimide, along a series of electrodes
      and onto the diagnostic chip. Upon reaching the diagnostic chip, electronic
      hybridization was performed for a competitive reverse dot blot assay. The
      electronic assay showed a specific to nonspecific ratio in excess of 20:1. These
      results suggested that this type of structure might be of practical consequence
      with the development of a microlaboratory for biowarfare applications.

PMID- 11339998
TI  - Simultaneous measurement of cellular respiration and acidification with a single
      CMOS ISFET.
AB  - In vivo, the pH value and oxygen partial pressure are the most important physico
      chemical parameters in the microenvironment of human tissues. In vitro, the
      extracellular acidification rate of cell cultures is an indicator of global
      cellular metabolism, while the rate of oxygen consumption is a measure of
      mitochondrial activity. Earlier approaches had the disadvantage that these two
      values had to be measured with two separate sensors at different loci within the
      tissue or cell culture. Furthermore, conventional Clark-type oxygen sensors are
      not very compatible for miniaturisation, making it impossible to measure at small
      cell volumes or even at the single cell level. We have, therefore, developed an
      ISFET based sensor structure which is able to measure both pH and oxygen partial
      pressure. This sensor structure was tested in vitro for simultaneous records of
      cellular acidification and respiration rates at the same site within the cell
      culture. This sensor is manufactured by a CMOS-process.

PMID- 11339999
TI  - Electrical properties of a light-addressable microelectrode chip with high
      electrode density for extracellular stimulation and recording of excitable cells.
AB  - A light-addressable microelectrode chip with 3600 TiN electrodes was fabricated.
      Amorphous silicon (a-Si:H) serves as a photo conductor. The electrodes on the
      chip are addressed by a laser spot and electrical properties of the system are
      determined. DC measurements show a dark to bright dynamic of 10(6)-10(7). The AC
      impedance dynamic @ 1 kHz/100 mV and thus the signal-to-noise-ratio is determined
      to 60. This value is quite sufficient for electrophysiological measurements. For
      the first time, recordings from cardiac myocytes are reported using the principle
      of light-addressing. Measurements were done with a standard laser scan microscope
      (Zeiss LSM 410).

PMID- 11340000
TI  - Voltammetric biosensors for the determination of formate and glucose-6-phosphate
      based on the measurement of dehydrogenase-generated NADH and NADPH.
AB  - This paper describes the development of a modified electrode for the
      electrocatalytic oxidation of beta-nicotinamide adenine dinucleotide (beta-NADH)
      and beta-nicotinamide adenine dinucleotide phosphate (beta-NADPH) using
      electropolymerised 3,4-dihydroxybenzaldehyde (3,4-DHB). Two voltammetric
      biosensors using enzyme-immobilised membranes were constructed for the
      determination of formic acid and glucose-6-phosphate (G6P), respectively. The
      formic acid biosensor based on the combination of formate dehydrogenase (FDH)
      modified membrane with 3,4-DHB-coated glassy carbon electrode is one to two
      orders more sensitive (LOD, 5.0x10(-5) M) than previously reported
      electrochemical biosensors. Similarly, lower detection limit (4.0x10(-5) M) for
      the measurement of G6P was achieved using glucose-6-phosphate dehydrogenase
      (G6PDH) in the presence of beta-NADP(+). The interference of uric acid and
      ascorbate was minimised by incorporating an additional membrane modified with
      uricase and ascorbate oxidase, respectively. The biosensing scheme developed in
      this study can be adopted universally with a number of dehydrogenases for the
      detection of different substrates.

PMID- 11340001
TI  - An immunosensor with potential for the detection of viral antigens in body
      fluids, based on surface second harmonic generation.
AB  - Field methods of assessing the immune status of animals are required to optimise
      vaccination programmes to control bovine viral diarrhoea (BVD) virus. An
      optoelectronic immunosensor was evaluated for the detection of viral antigens in
      a crude cell lysate in a pilot study. Binding of (BVD) virus antigen by two
      monoclonal antibodies immobilised on two different media (ELISA plate wells, and
      glass coverslips) was detected and quantified using the laser induced surface
      second harmonic generation (SSHG) technique. The results for both assays were
      correlated with an enzyme-linked immunoassay (ELISA) used for the diagnosis of
      BVD virus infection in cattle (ELISA plate; R(2)=0.86, coverslips; Exp. 1;
      R(2)=0.75, Exp. 2; R(2)=0.67). The method will allow rapid detection of antigens
      in the body fluids of farm animals.

PMID- 11340002
TI  - Improving clinical decisions and outcomes with information: a review.
AB  - The clinical information available to clinicians is expanding rapidly. It can
      enhance clinical decision-making, but it can also confuse the process. To be most
      useful, information should be available at the time and place it is needed and be
      specific to the task at hand. In the new paradigm of medicine, one based on
      continuous quality improvement, useful information must be relevant to both the
      processes and outcomes of care. Clinical practice guidelines have become
      increasingly popular for improving the quality of health care. The field of
      medical informatics can bring cogent information to the point where decisions are
      being made to augment quality improvement activities in general, and practice
      guidelines in particular. However, such innovations are dependent on the type,
      quantity, and quality of information available. This article discusses when
      guidelines can enhance the quality and outcomes of care and how medical
      informatics can help achieve these goals. In particular, the barriers to the
      broad implementation of electronic medical records in a variety of health care
      settings are explored.

PMID- 11340003
TI  - Mining time dependency patterns in clinical pathways.
AB  - Clinical pathways are widely adopted by many large hospitals around the world in
      order to provide high-quality patient treatment and reduce the length of hospital
      stay of each patient. The development of clinical pathways is a lengthy process,
      and may require the collaboration among physicians, nurses, and staffs in a
      hospital. However, the individual differences cause great variances in the
      execution of clinical pathways. It calls for a more dynamic and adaptive process
      to improve the performance of clinical pathways. This paper reports a data mining
      technique we have developed to discover the time dependency pattern of clinical
      pathways for managing brain stroke. The mining of time dependency pattern is to
      discover patterns of process execution sequences and to identify the dependent
      relation between activities in a majority of cases. By obtaining the time
      dependency patterns, we can predict the paths for new patients when he/she is
      admitted into a hospital; in turn, the health care procedure will be more
      effective and efficient.

PMID- 11340004
TI  - The personal internetworked notary and guardian.
AB  - In this paper, we propose a secure, distributed and scaleable infrastructure for
      a lifelong personal medical record system. We leverage on existing and widely
      available technologies, like the Web and public-key cryptography, to define an
      architecture that allows patients to exercise full control over their medical
      data. This is done without compromising patients' privacy and the ability of
      other interested parties (e.g. physicians, health-care institutions, public
      health researchers) to access the data when appropriately authorized. The system
      organizes the information as a tree of encrypted plain-text XML files, in order
      to ensure platform independence and durability, and uses a role-based
      authorization scheme to assign access privileges. In addition to the basic
      architecture, we describe tools to populate the patient's record with data from
      hospital databases and the first testbed applications we are deploying.

PMID- 11340005
TI  - Patient data confidentiality and patient rights.
AB  - There has been a recent trend to gather and record more comprehensive and more
      detailed personal medical information in computerized databases. Retrieval and
      access are much easier from electronic records than from hard copies stored in
      the archives of care-providing institutions. The Institute of Medicine voiced
      concern that these developments raised numerous problematic issues, the most
      disturbing of which is a much more widespread and systematic violation of privacy
      via what they called 'authorized abuse', i.e. authorized users abusing their
      access privileges. Other worries stemmed from the sharing of patient information
      among different entities. Multitudes of organizations receive information about
      patients' health records, often without their knowledge or consent. These include
      care providers, insurers, pharmacists, employers, life insurance companies and
      marketing firms. This article addresses the issues of medical data ownership and
      some health data-recording problems to which we propose co-ownership and co
      documentation as part of the solution. We believe that a cooperative approach
      will help to maintain greater accuracy of personal medical data, written in
      language that can be shared and understood by the consumers and not one couched
      in terminology understandable only to professional personnel and to delegate the
      power to the patient to decide when and to whom to give authorization for its use
      by a third party and for research.

PMID- 11340006
TI  - A systematic approach for analysis and design of secure health information
      systems.
AB  - A toolset using object-oriented techniques including the nowadays popular unified
      modelling language (UML) approach has been developed to facilitate the different
      users' views for security analysis and design of health care information systems.
      Paradigm and concepts used are based on the component architecture of information
      systems and on a general layered security model. The toolset was developed in
      1996/1997 within the ISHTAR project funded by the European Commission as well as
      through international standardisation activities. Analysing and systematising
      real health care scenarios, only six and nine use case types could be found in
      the health and the security-related view, respectively. By combining these use
      case types, the analysis and design of any thinkable system architecture can be
      simplified significantly. Based on generic schemes, the environment needed for
      both communication and application security can be established by appropriate
      sets of security services and mechanisms. Because of the importance and the basic
      character of electronic health care record (EHCR) systems, the understanding of
      the approach is facilitated by (incomplete) examples for this application.

PMID- 11340007
TI  - Modeling a medical environment: an ontology for integrated medical informatics
      design.
AB  - Modern medical environments have seen an increase in technological complexity and
      pressures of handling more patients with fewer resources, resulting in higher
      demands on medical practitioners. Medical informatics designers will have to
      focus on the problem of organizing medical information more effectively to enable
      practitioners to cope with these challenges. This article addresses this research
      problem for the particular area of medical problem solving in patient care.
      First, we describe a traditional modeling approach for medical reasoning used as
      a basis for developing some decision support systems. We argue these models may
      be faithful to what is known about biomedical knowledge, but they have
      limitations for human problem solving, especially in unanticipated situations.
      Second, we present an ontological framework, known as the abstraction hierarchy
      (Rasmussen, IEEE Trans. Man. Cybernetics 15 (1985) 234-243), for integrating
      patient representations that are faithful to existing biomedical knowledge and
      that are consistent with what is known about human problem solving. Through an
      example of a critical event in the operating room, we reveal how this framework
      can support medical problem solving in unanticipated situations. Third, we show
      how to use these representations as a frame of reference for mapping medical
      roles, responsibilities, sensors, and controls in an operating room context.
      Finally, we provide some insight for medical informatics designers in using this
      framework to design novel training programs and human-computer displays.

PMID- 11340008
TI  - Vascular brachytherapy: from investigation to approval.

PMID- 11340009
TI  - Intracoronary radiation with gamma wire inhibits recurrent in-stent restenosis.
AB  - To study the safety and efficacy of intracoronary gamma radiation delivered via a
      new high-activity (192)Ir source wire for the treatment of in-stent restenosis.
      In-stent restenosis results from neointimal tissue proliferation especially in
      its diffused form and presents a therapeutic challenge. Gamma radiation has been
      shown to decrease neointima formation within stents in animal models and in
      initial clinical trials. A total of 26 patients with in-stent restenosis
      underwent successful intervention and was treated with open-label (192)Ir using a
      high-activity line source. The specific activity of the source wire was 372+/-51
      mCi, and the dwell time was 10.8+/-1.9 min. Primary endpoints were freedom from
      death, myocardial infraction (MI), and repeat target lesion revascularization
      (TLR) at 6 months. Secondary endpoints included angiographic restenosis and
      intravascular ultrasound (IVUS) neointimal hyperplasia. Procedural success was
      high (96.2%), and in-hospital and 30-day complications were low with no deaths,
      MI, or requirement for repeat revascularization. At 6 months, event-free survival
      was 85%: one patient required repeat PTCA, one underwent bypass surgery, and two
      had an MI. Baseline lesion length measured 15.77 mm. Follow-up angiography was
      available in 21/25 (84%) patients. The binary restenosis rates were 19.0% (4/21)
      in-stent and 23.8% (5/21) in-lesion. Follow-up IVUS was available in 20/25
      patients. There was no increase in intimal hyperplasia from postintervention to
      follow-up (3.11.8 vs. 3.41.8 mm(2); P=.32). Eight patients had a reduction of
      neointimal intimal tissue at follow-up. These results indicate that intracoronary
      gamma radiation with the Angiorad source wire is safe and effective in preventing
      in-stent restenosis.

PMID- 11340010
TI  - Samarium-153 for intravascular irradiation therapy with liquid-filled balloons to
      prevent restenosis: acute and long-term results in a hypercholesterolemic rabbit
      restenosis model.
AB  - BACKGROUND: It has been shown that irradiation with either beta and gamma sources
      inhibit neointimal formation. Samarium-153 ((153)Sm) is an isotope with 0.8 MeV,
      subdivided in three different beta energies and 103 keV of gamma energy. This
      compound has been tested and used in humans for palliation of pain from bone
      metastases. The aim of the present study was to evaluate the feasibility and
      efficacy of brachytherapy with (153)Sm-filled balloon to inhibit neointimal
      formation in rabbits after balloon overstretch injury. METHODS: Nineteen rabbits
      underwent balloon injury in their iliac arteries. In 12 animals (control),
      oversized balloons filled with saline solution were inflated up to 5 atm for a
      period of 5 min. In 7 rabbits, the same procedure was performed but using
      balloons filled with (153)Sm. In all cases, both iliac arteries were treated. The
      prescribed radiation dose was 15 Gy at 1 mm depth. After 30 days, the animals
      were sacrificed and their arterial segments were analyzed. Radiation exposure at
      the animal chest to the table and at a distance of 1 m from the table was
      measured. RESULTS: Histopathologic analysis showed a striking reduction in the
      amount of neointima in the irradiated arteries compared with control vessels
      (0.36+/-0.21 vs. 1.07+/-0.56 mm(2), P<.01). The dose delivered to the animal
      chest was 21.5 mR/h, whereas only 1.9 mR/h was measured at the table and
      virtually no radiation could be detected at a distance of 1 m from the table.
      CONCLUSIONS: Brachytherapy with (153)Sm was feasible with minimal personnel
      exposure radiation and effectively inhibited neointimal formation in this
      experimental model. These results warrant further experimental and clinical
      investigations.

PMID- 11340011
TI  - Differential remodeling after balloon overstretch injury and either beta- or
      gamma-intracoronary radiation of porcine coronary arteries.
AB  - BACKGROUND: Restenosis is a consequence of both neointimal hyperplasia and vessel
      remodeling. Prior studies have shown that intracoronary radiation (IR) prevents
      neointima accumulation, but its contribution to vessel remodeling is unknown. The
      purpose of this study was to evaluate the effect of IR on differential vascular
      remodeling after balloon angioplasty in porcine coronary arteries. METHODS: A
      total of 20 juvenile swine (30 coronary arteries) were subjected to overstretch
      balloon injury (BI) followed by IR with either beta- or gamma-radiation ((90)Y or
      (192)Ir). After 2 weeks following treatment, serial tissue sections were
      perfusion fixed and stained by hematoxylin and eosin (H&E), Verhoeff von Giesson
      (VVG), or Masson Trichrome. Adventitial area (AA), lumen area (LA), vessel area
      (VA), intimal area (IA), and IA corrected for medial fracture length (IA/FL) were
      quantified by digital image analysis. The vessel circumference was divided into
      two regions containing (1) the undisrupted region (UReg) with the undisrupted arc
      of media and internal elastic lamina (IEL) and (2) the disrupted region (DReg)
      with the disrupted arc between the medial tears. Quantitative regional analysis
      was performed by (1) measuring the IEL to define the UReg, (2) calculating the
      area of the UReg with the perimeter value derived from measurement of the IEL,
      and (3) calculating the DReg as follows: LA+IA-UReg. Immunohistochemical smooth
      muscle cell alpha-actin and Masson Trichrome were quantified by digital image
      analysis. RESULTS: The IA/FL was significantly smaller following treatment with
      (90)Y or (192)Ir vs. control (P<.01). A smaller AA was obtained following IR with
      both beta- and gamma-sources vs. control (P<.01). The UReg calculation was
      smaller in the irradiated arteries as compared to control (beta: 2.3+/-0.4 mm(2),
      gamma: 2.1+/-0.5 mm(2), P<.01 vs. control; control: 3.6+/-0.7 mm(2)). In
      contrast, the DReg was increased following IR, as demonstrated by the FL and the
      calculated area of the injured segment (control: 2.7+/-0.5 mm(2); beta: 5.5+/-1.1
      mm(2), gamma: 5.5+/-1.1 mm(2), P<.01 vs. control). Adventitial alpha-actin
      positive cell density (CD) was decreased after IR; however, the collagen density
      was similar. In contrast, the neointimal collagen density in the injured segment
      was significantly decreased following IR. CONCLUSION: We consider that the global
      arterial remodeling after IR is a heterogeneous process that includes the absence
      of retraction in an UReg and a positive remodeling in the DReg as shown in the
      porcine coronary model. These changes in adventitia and neointima appear to
      contribute to differential vascular remodeling caused by IR in injured vessels.

PMID- 11340012
TI  - Treatment planning dosimetric parameters for a (90)Y coil source used in
      intravascular brachytherapy.
AB  - BACKGROUND: (90)Y coil sources have been used in animal and clinical trials for
      treatment of restenosis in intravascular brachytherapy (IVBT). This study aims to
      determine the American Association of Physicists in Medicine (AAPM) Task Group-60
      (TG-60) dosimetric quantities in regions surrounding the balloon wall for use in
      treatment planning computer systems. METHODS: The Monte Carlo method was used to
      determine the dose distribution, using MCNP4B2 code. The coil source was modeled
      by a hollow cylinder of 2.9 cm length centered in a balloon (2.5 mm diameter)
      filled with carbon dioxide (CO(2)) at 5 atm. Scoring voxels consisted of
      contiguous annular disk shells with 0.1 mm spacing in the radial direction and
      0.2 mm spacing in the longitudinal direction. The scoring region ranges from the
      center of the source to 1.0 cm in the longitudinal direction, and from 0.13 to 1
      cm in the radial direction. In the plane containing the source axis, the Monte
      Carlo-generated doses in rectilinear coordinates are converted to polar
      coordinates. RESULTS: The dose rate of the source is provided in both Cartesian
      and polar coordinates. The dose rate constant [D(r(0),theta(0))], anisotropy
      function [F(r,theta)], and radial dose function [g(r)] were generated from these
      values and listed in tabular format. At shallow angles and longer distances from
      the source center, large values of the anisotropy function resulted, deviating
      two orders of magnitude from unity. CONCLUSIONS The doses given to the intima,
      media, and adventitia are very crucial quantities in IVBT. The calculated TG-60
      dosimetric quantities, used commonly in conventional brachytherapy applications,
      provide a means for the user to determine the three-dimensional dose surrounding
      the balloon catheter. These parameters can be used in future treatment planning
      system for IVBT. We also discuss the need to develop a new formalism specific to
      longer sources used in IVBT.

PMID- 11340013
TI  - Shielding effects of metallic encapsulations and radiographic contrast agents for
      catheter-based intravascular brachytherapy.
AB  - PURPOSE/OBJECTIVE: Both photon- and beta-emitting radionuclides for intravascular
      brachytherapy (IVB) are under active investigation for prevention of restenosis
      following conventional angioplasty with or without stents. High atomic number
      materials are usually present in the coronary vessels undergoing treatment in the
      form of metallic encapsulations, stents, calcified plaque, or radiographic
      contrast agent. The high atomic number materials are likely to interfere with the
      photons and betas and, thus, change the dosimetry in the treatment volume. The
      purpose of this study is to investigate the shielding effects caused by the
      presence of high atomic number materials in IVB. MATERIALS AND METHODS: Dose
      rates at various distances in water, with and without the presence of various
      high atomic number materials, were calculated using Monte Carlo simulation
      techniques for photon and electron transport in extended media. The high atomic
      number materials investigated included titanium, stainless steel, calcified
      plaque, Hypaque, and Omnipaque. A wide range of monoenergetic photon and electron
      sources and several photon- and beta-emitting radionuclides, which have been
      under consideration for IVB, were used. The energy of the monoenergetic photon
      sources was in the range from 10 keV to 1 MeV, and that of the monoenergetic
      electron sources in the range from 0.5 to 2 MeV. Photon-emitting radionuclides
      (192)Ir, (125)I, and (103)Pd and beta-emitting radionuclides (90)Y, (32)P, and
      (188)Re were also considered. RESULTS: It was found that the high atomic number
      materials interfere considerably with the transport of photons of relatively low
      energies (below 40 keV) and all electron sources. When the energy of photon
      exceeds 100 keV, the interference becomes minimum for the high atomic number
      materials that are likely to be present in clinical situations. The shielding
      correction factors (SCFs) for dose rate at 2 mm from center were essentially 1.00
      for photon energies above 100 keV; as the energy decreased below 100 keV, the SCF
      became smaller reaching a value of almost 0 for the lowest energy studied, 10
      keV. For the photon source of (192)Ir, the SCF was essentially 1.00; while for
      the photon sources of (125)I and (103)Pd, shielding corrections were considerably
      lower than 1.00 depending on the type and thickness of the high atomic number
      material. For the beta emitting sources, the shielding effect can be expressed as
      a loss in effective penetration depth. This loss depends both on the material and
      its thickness. For titanium and stainless steel, the loss of range was about two
      and four times the thickness of the metal. CONCLUSIONS: The effects of high
      atomic number materials, such as metallic stents, calcified plaque, and contrast
      agents are minimal for high energy photon emitters, such as (192)Ir. The effects
      are pronounced for beta emitters and low energy photon emitters, and must be
      included in dosimetry planning.

PMID- 11340014
TI  - Is there a relation between 'candy wrapper,' prevention of (for instance)
      coronary artery disease, and therapy of postdiscectomy syndrome by irradiation?

PMID- 11340015
TI  - Clinical trials of vascular brachytherapy for in-stent restenosis: update.
AB  - Vascular brachytherapy has become the therapeutic strategy of choice for in-stent
      restenosis. Clinical trials evaluating the effectiveness and safety of this
      technology have enrolled nearly 4000 patients using both gamma and beta emitters.
      At present, ongoing controversies include optimal dosimetry, whether beta
      emitters are as effective as gamma and whether centering delivery systems perform
      better than non-centering systems. Complications of brachytherapy such as edge
      effect, late thrombosis and late restenosis have received increasing attention.
      This review provides an update of the current status of clinical trials utilizing
      vascular brachytherapy to prevent the recurrence of in-stent restenosis.

PMID- 11340016
TI  - Successful treatment of intimal hyperplasia in renal arteries by endovascular
      brachytherapy.
AB  - PURPOSE: The present study shows the possibility of preventing restenosis of
      renal arteries by endovascular brachytherapy. METHODS AND MATERIALS: We present a
      patient suffering from rapid restenosis of both renal arteries with decreasing
      renal function. Percutaneous transluminal angioplasty (PTA) and stent
      implantation were unable to stop hypertension and to stabilize renal function.
      Both renal arteries and the right pole artery were treated by endovascular
      brachytherapy in one session. RESULTS: Six months after intervention,
      intraarterial digital subtraction angiography (DSA) showed no evidence of
      recurrence, and the blood pressure remained normal without medical treatment.
      CONCLUSION: Endovascular brachytherapy can help to prevent restenosis in renal
      arteries. It is possible to treat both renal arteries and one pole artery in one
      session without any disadvantage.

PMID- 11340017
TI  - Bringing vascular brachytherapy to the US forefront: FDA approves two radiation
      systems for in-stent restenosis.

PMID- 11340019
TI  - Depression and heart disease.

PMID- 11340018
TI  - A new treatment for peripheral arterial disease.

PMID- 11340020
TI  - Who is harmed by hostility?

PMID- 11340021
TI  - Angioplasty keeps getting better.

PMID- 11340022
TI  - Walking and gardening beneficial for heart disease patients.

PMID- 11340023
TI  - Alcohol and pain from blocked leg arteries.

PMID- 11340024
TI  - Ask the doctor. I've had a leaky mitral valve for many years. My doctor thinks I
      should have the valve replaced fairly soon. Is there anything I can do to delay
      this surgery?

PMID- 11340025
TI  - Diabetes treatment. The tried and true, and what's new.

PMID- 11340026
TI  - Nutrition. Vitamin C.

PMID- 11340027
TI  - Orthopedics. Remedies for aching knees.

PMID- 11340028
TI  - Skin disease. Eczema.

PMID- 11340029
TI  - By the way, doctor... Drugs for atrial fibrillation. I had atrial fibrillation
      and was zapped back into sinus rhythm several weeks ago. It seems like I'm going
      to have to take either aspirin or Coumadin. Which is better, and why?

PMID- 11340031
TI  - Arteriosclerosis and emotional disorders.

PMID- 11340030
TI  - Bipolar disorder -- Part I.

PMID- 11340032
TI  - Atypical antipsychotic drugs: how much better are they?

PMID- 11340033
TI  - How women handle stress: is there a difference?

PMID- 11340034
TI  - Some physical effects of emotional violence.

PMID- 11340035
TI  - Peripheral artery disease. Part I: causes and symptoms.

PMID- 11340036
TI  - Antioxidant supplements and the heart: what went wrong.

PMID- 11340037
TI  - Medical memo. Winning at the losing game.

PMID- 11340038
TI  - Another chapter in the heart and estrogen story.

PMID- 11340039
TI  - Fabulous folate.

PMID- 11340040
TI  - Alternatives to hysterectomy.

PMID- 11340041
TI  - By the way, doctor. I know about the benefits of liposuction. But what about the
      downside? Does it cause much pain? How long does it take to recover? What about
      regaining fat in the same location?

PMID- 11340042
TI  - Increasing the sink:source balance enhances photosynthetic rate of 1-year-old
      balsam fir foliage by increasing allocation of mineral nutrients.
AB  - To determine the impact of altering the sink:source balance on gas exchange rates
      in 1-year-old foliage of balsam fir (Abies balsamea (L.) Mill.), seedlings were
      either debudded before the growing season began or left intact. To assess
      alternative explanations for the observed photosynthetic response, additional
      seedlings were variously root pruned, shaded, drought stressed or deprived of
      fertilizer in combination with debudding. Foliar gas exchange rates and
      carbohydrate concentrations, xylem water potential and current-year growth were
      measured on three occasions spanning the shoot extension period. In addition,
      growth, foliar concentrations of chlorophyll, nitrogen, phosphorus and potassium,
      chlorophyll fluorescence and photosynthetic rate at different CO2 concentrations
      were determined 1 month after shoot extension ceased. Debudded seedlings had
      higher photosynthetic rates than budded seedlings, and the difference increased
      as the growing season progressed. We observed no evidence that debudding
      increased photosynthetic rate by improving water relations or by reducing foliar
      carbohydrate concentrations. Debudding increased foliar concentrations of
      nitrogen, phosphorus, potassium and chlorophyll, as well as quantum yield and
      photochemical quenching as determined by chlorophyll fluorescence measurements.
      Therefore, we conclude that debudding increased the photosynthetic rate by
      increasing the allocation of nutrients to 1-year-old foliage, thereby enhancing
      the amount or activity, or both, of photosynthetic enzymes, as well as increasing
      chlorophyll concentration.

PMID- 11340043
TI  - Effects of drought stress and high density stem inoculations with Leptographium
      wingfieldii on hydraulic properties of young Scots pine trees.
AB  - We examined drought-induced changes in susceptibility of potted Scots pine (Pinus
      sylvestris L.) trees to a bark-beetle associated fungus (Leptographium
      wingfieldii Morelet, from the bark beetle Tomicus piniperda L.). Five-year-old
      field-grown trees were transplanted to 50-l pots and grown for 1 year before the
      treatments were applied. Trees in the drought treatment were subjected to several
      successive, 3-week-long drought cycles, with predawn water potential dropping
      below -2 MPa at peak drought intensity. The experimental drought cycles were more
      severe than the natural drought episodes usually recorded in Scots pine stands.
      Trees were then mass-inoculated with L. wingfieldii at a density close to the
      critical threshold density of inoculations (400 m(-2)) above which tree
      resistance is overcome. Inoculation of well-watered trees resulted in induced
      reaction zones around the inoculation points and very limited damage (resinosis)
      in the sapwood. Drought alone had no long-lasting consequences on tree water
      relations, except for a decrease in hydraulic conductance in the youngest
      segments of the main stem. However, the combination of mass-inoculation and
      drought stress after inoculation resulted in a dramatic loss of stem hydraulic
      conductivity that was paralleled by conspicuous damage to the sapwood (resinosis,
      drying and blue staining). There was a close correlation between amount of
      visible sapwood damage and loss of hydraulic conductivity. The intensity of
      induced reactions in the phloem was unaffected by drought stress. We conclude
      that tree defence against L. wingfieldii is decreased during severe drought
      stress, resulting in changes in the spread and action of the fungus in the
      sapwood but not in the phloem.

PMID- 11340044
TI  - Effect of elevated CO2 on monoterpene emission of young Quercus ilex trees and
      its relation to structural and ecophysiological parameters.
AB  - We investigated growth, leaf monoterpene emission, gas exchange, leaf structure
      and leaf chemical composition of 1-year-old Quercus ilex L. seedlings grown in
      ambient (350 microl l(-1)) and elevated (700 microl l(-1)) CO2 concentrations
      ([CO2]). Monoterpene emission and gas exchange were determined at constant
      temperature and irradiance (25 degrees C and 1000 micromol m(-2) s(-1) of
      photosynthetically active radiation) at an assay [CO2] of 350 or 700 microl l(
      1). Measurements were made on intact shoots after the end of the growing season
      between mid-October and mid-February. On average, plants grown in elevated [CO2]
      had significantly increased foliage biomass (about 50%). Leaves in the elevated
      [CO2] treatment were significantly thicker and had significantly higher
      concentrations of cellulose and lignin and significantly lower concentrations of
      nitrogen and minerals than leaves in the ambient [CO2] treatment. Leaf dry matter
      density and leaf concentrations of starch, soluble sugars, lipids and hemi
      cellulose were not significantly affected by growth in elevated [CO2].
      Monoterpene emissions of seedlings were significantly increased by elevated [CO2]
      but were insensitive to short-term changes in assay [CO2]. On average, plants
      grown in elevated [CO2] had 1.8-fold higher monoterpene emissions irrespective of
      the assay [CO2]. Conversely, assay [CO2] rapidly affected photosynthetic rate,
      but there was no apparent long-term acclimation of photosynthesis to growth in
      elevated [CO2]. Regardless of growth [CO2], photosynthetic rates of all plants
      almost doubled when the assay [CO2] was switched from 350 to 700 microl l(-1). At
      the same assay [CO2], mean photosynthetic rates of seedlings in the two growth
      CO2 treatments were similar. The percentage of assimilated carbon lost as
      monoterpenes was not significantly altered by CO2 enrichment. Leaf emission rates
      were correlated with leaf thickness, leaf concentrations of cellulose, lignin and
      nitrogen, and total plant leaf area. In all plants, monoterpene emissions
      strongly declined during the winter independently of CO2 treatment. The results
      are discussed in the context of the acquisition and allocation of resources by Q.
      ilex seedlings and evaluated in terms of emission predictions.

PMID- 11340045
TI  - Influence of nitrogen and phosphorous availability and ozone stress on Norway
      spruce seedlings.
AB  - Four-year-old Norway spruce (Picea abies L. (Karst.)) seedlings were exposed to
      ambient and elevated (1.5 x ambient in 1997 and 1.6 x ambient in 1998) ozone
      concentrations [O3] and three nitrogen (N) and two phosphorus (P) availabilities:
      "optimal" values (control); 70% of the control N and P values (LN and LP); and
      150% of the control N value (HN). Treatments were applied in an open-field ozone
      fumigation facility during the 1997 and 1998 growing seasons. Effects on growth,
      mineral and pigment concentrations, stomatal conductance and ultrastructure of
      needles were studied. The HN treatment increased growth significantly, whereas
      elevated [O3] had a slight or variable impact on growth and biomass allocation in
      all N treatments. Although there were no significant effects of the LP treatment
      on plant growth during the second year, there was a reduction in 1-year-old shoot
      dry mass in the elevated O3 + LP treatment at the end of the experiment. There
      were no significant treatment effects on mineral concentrations of current-year
      and 1-year-old needles at the final harvest. In response to the HN treatment,
      chlorophyll a and b and carotenoid concentrations increased significantly in
      current-year needles. Chlorophyll a/b ratio decreased in response to elevated
      [O3] alone, but increased in seedlings in the O(3) + LP treatment. Stomatal
      conductance of current-year needles decreased with increasing N availability, but
      increased in response to elevated [O3]. However, the O3-induced increase in
      stomatal conductance was less in the LN and LP treatments than in the control
      treatment. In chloroplasts of current-year needles, increased N availability
      decreased mean starch grain area, but increased the number of plastoglobuli. We
      conclude that Norway spruce seedlings are relatively tolerant to slightly
      elevated [O3], and that nitrogen and phosphorus imbalances do not greatly affect
      the influence of O3 on this species when the exposure lasts for two growing
      seasons or less.

PMID- 11340046
TI  - Distinct effects of auxin and light on adventitious root development in
      Eucalyptus saligna and Eucalyptus globulus.
AB  - Adventitious rooting is essential for vegetative propagation of woody species. We
      studied the effects of auxin and light on the development of adventitious roots
      in cuttings obtained from seedlings of Eucalyptus saligna Smith and E. globulus
      Labill in an attempt to characterize the adventitious rooting process and
      identify factors controlling rhizogenesis. Root development was scored as rooting
      percentage, root density (roots per rooted cutting), mean rooting time and root
      length. In both species, rooting time was reduced in the presence of auxin.
      Cuttings from 2-month-old E. saligna seedlings were responsive to lower auxin
      concentrations than comparable cuttings from E. globulus seedlings. Cuttings from
      3-month-old E. saligna seedlings rooted promptly and rooting was not
      significantly affected by light conditions. In contrast, rooting of cuttings from
      3-month-old E. globulus seedlings exhibited recalcitrant behavior and no roots
      were formed if illuminated during the root formation phase. Effective root
      regeneration of E. globulus cuttings was obtained by a 4-day exposure to 10 mg l(
      1) IBA and culture in darkness during the root formation step. Loss of rooting
      capacity with seedling age was more pronounced in E. globulus than in E. saligna.
      The possibility of switching adventitious rooting off and on by manipulating
      light regime and exogenous auxin supply in E. globulus, and the constitutive
      nature of rooting in E. saligna may provide useful models for examining the
      rooting process at the biochemical and molecular levels in Eucalyptus.

PMID- 11340047
TI  - Effects of soil temperature on biomass and carbohydrate allocation in Scots pine
      (Pinus sylvestris) seedlings at the beginning of the growing season.
AB  - We studied effects of soil temperature on shoot and root extension growth and
      biomass and carbohydrate allocation in Scots pine (Pinus sylvestris L.) seedlings
      at the beginning of the growing season. One-year-old Scots pine seedlings were
      grown for 9 weeks at soil temperatures of 5, 9, 13 and 17 degrees C and an air
      temperature of 17 degrees C. Date of bud burst, and the elongation of shoots and
      roots were monitored. Biomass of current and previous season roots, stem and
      needles was determined at 3-week intervals. Starch, sucrose, glucose, fructose,
      sorbitol and inositol concentrations were determined in all plant parts except
      new roots. The timing of both bud burst and the onset of root elongation were
      unaffected by soil temperature. At Week 9, height growth was reduced and root
      extension growth was much less at a soil temperature of 5 degrees C than at
      higher soil temperatures. Total seedling biomass was lowest in the 5 degrees C
      soil temperature treatment and highest in the 13 degrees C treatment, but there
      was no statistically significant difference in total biomass between seedlings
      grown at 13 and 17 degrees C. In response to increasing soil temperature, below
      ground biomass increased markedly, resulting in a slightly higher allocation of
      biomass to below-ground parts. Among treatments, root length was greatest at a
      soil temperature of 17 degrees C. The sugar content of old roots was unaffected
      by soil temperature, but the sugar content of new needles increased with
      increasing soil temperature. The starch content of all seedling parts was lowest
      in seedlings grown at 17 degrees C. Otherwise, soil temperature had no effect on
      seedling starch content.

PMID- 11340048
TI  - Medium-term sap flux monitoring in a Scots pine stand: analysis of the
      operability of the heat dissipation method for hydrological purposes.
AB  - The operability of Granier-type heat dissipation sap flow meters for the medium
      term monitoring of Scots pine transpiration was tested. Three sensors that had
      been working for 3 years were duplicated by inserting new sensors in the same
      trees. The new sensors operated simultaneously with the old sensors for 18
      months. Analysis of the temporal patterns of thermal dissipation of the sensors
      showed a slight, but significant decrease in all sensors, indicating the
      conservation of sapwood thermal properties. Although there was a high correlation
      between sap flux densities registered by the old and new sensors, significant
      differences in sap flux densities between the duplicated sensors were detected.
      Such differences could not be attributed to tissue injury around the sensors or
      to loss of sensitivity of the old sensors, because two of the old sensors
      registered higher flux rates than the new sensors. No instrumental error to
      explain the sap flux differences was found. Because the new sensors were
      installed at some angular distance from the old sap flow meters to avoid thermal
      interferences, it was inferred that the observed sap flux differences between
      duplicate sensors were the result of an azimuthal sap flow pattern.

PMID- 11340049
TI  - Effect of feeding by the western conifer seed bug, Leptoglossus occidentalis, on
      the major storage reserves of developing seeds and on seedling vigor of Douglas
      fir.
AB  - The impact of feeding by the western conifer seed bug (Leptoglossus occidentalis
      Heidemann) on storage reserves of developing seeds of Douglas-fir (Pseudostuga
      menziesii (Mirb.) Franco) was studied by caging nymphal and adult seed bugs on
      cones during late-season development, and nymphs on cones during early, mid- and
      late-season development. Analysis of the major storage reserves of partially
      damaged seeds revealed that late-season feeding by each life stage and feeding by
      nymphs at all three stages of cone development significantly reduced the amounts
      of lipid and buffer-insoluble (crystalloid) protein in seeds at harvest by up to
      78 and 97%, respectively. Seeds showing light to moderate damage on radiographs
      did not exhibit a reduction in the amount of buffer-soluble (matrix) protein.
      Seeds damaged by feeding during early development compensated in part by
      continuing to synthesize lipid and crystalloid protein. Light or moderate damage
      to mature Douglas-fir seeds exposed to L. occidentalis in the laboratory reduced
      seedling emergence by > 80%, but the seedlings that emerged successfully appeared
      to suffer no adverse effects when grown under standard nursery conditions.

PMID- 11340050
TI  - Hydrogen bonding, base stacking, and steric effects in dna replication.
AB  - Understanding the mechanisms by which genetic information is replicated is
      important both to basic knowledge of biological organisms and to many useful
      applications in biomedical research and biotechnology. One of the main functions
      of a DNA polymerase enzyme is to help DNA recognize itself with high specificity
      when a strand is being copied. Recent studies have shed new light on the question
      of what physical forces cause a polymerase enzyme to insert a nucleotide into a
      strand of DNA and to choose the correct nucleotide over the incorrect ones. This
      is discussed in the light of three main forces that govern DNA recognition: base
      stacking, Watson-Crick hydrogen bonding, and steric interactions. These factors
      are studied with natural and structurally altered DNA nucleosides.

PMID- 11340051
TI  - Structures and proton-pumping strategies of mitochondrial respiratory enzymes.
AB  - Enzymes of the mitochondrial respiratory chain serve as proton pumps, using the
      energy made available from electron transfer reactions to transport protons
      across the inner mitochondrial membrane and create an electrochemical gradient
      used for the production of ATP. The ATP synthase enzyme is reversible and can
      also serve as a proton pump by coupling ATP hydrolysis to proton translocation.
      Each of the respiratory enzymes uses a different strategy for performing proton
      pumping. In this work, the strategies are described and the structural bases for
      the action of these proteins are discussed in light of recent crystal structures
      of several respiratory enzymes. The mechanisms and efficiency of proton
      translocation are also analyzed in terms of the thermodynamics of the substrate
      transformations catalyzed by these enzymes.

PMID- 11340052
TI  - Mass spectrometry as a tool for protein crystallography.
AB  - Atomic resolution structure determinations of proteins by X-ray crystallography
      are formidable multidisciplinary undertakings, requiring protein construct
      design, expression and purification, crystallization trials, phase determination,
      and model building. Modern mass spectrometric methods can greatly facilitate
      these obligate tasks. Thus, mass spectrometry can be used to verify that the
      desired protein construct has been correctly expressed, to define compact domains
      in the target protein, to assess the components contained within the protein
      crystals, and to screen for successful incorporation of seleno-methionine and
      other heavy metal reagents used for phasing. In addition, mass spectrometry can
      be used to address issues of modeling, topology, and side-chain proximity. Here,
      we demonstrate how rational use of mass spectrometry assists and expedites high
      resolution X-ray structure determination through each stage of the process of
      protein crystallography.

PMID- 11340053
TI  - A structural view of cre-loxp site-specific recombination.
AB  - Structural models of site-specific recombinases from the lambda integrase family
      of enzymes have in the last four years provided an important new perspective on
      the three-dimensional nature of the recombination pathway. Members of this
      family, which include the bacteriophage P1 Cre recombinase, bacteriophage lambda
      integrase, the yeast Flp recombinase, and the bacterial XerCD recombinases,
      exchange strands between DNA substrates in a stepwise process. One pair of
      strands is exchanged to form a Holliday junction intermediate, and the second
      pair of strands is exchanged during resolution of the junction to products.
      Crystal structures of reaction intermediates in the Cre-loxP site-specific
      recombination system, together with recent biochemical studies in the field,
      support a "strand swapping" model for recombination that does not require branch
      migration of the Holliday junction intermediate in order to test homology between
      recombining sites.

PMID- 11340054
TI  - Probing the relation between force--lifetime--and chemistry in single molecular
      bonds.
AB  - On laboratory time scales, the energy landscape of a weak bond along a
      dissociation pathway is fully explored through Brownian-thermal excitations, and
      energy barriers become encoded in a dissociation time that varies with applied
      force. Probed with ramps of force over an enormous range of rates (force/time),
      this kinetic profile is transformed into a dynamic spectrum of bond rupture force
      as a function of loading rate. On a logarithmic scale in loading rate, the force
      spectrum provides an easy-to-read map of the prominent energy barriers traversed
      along the force-driven pathway and exposes the differences in energy between
      barriers. In this way, the method of dynamic force spectroscopy (DFS) is being
      used to probe the complex relation between force-lifetime-and chemistry in single
      molecular bonds. Most important, DFS probes the inner world of molecular
      interactions to reveal barriers that are difficult or impossible to detect in
      assays of near equilibrium dissociation but that determine bond lifetime and
      strength under rapid detachment. To use an ultrasensitive force probe as a
      spectroscopic tool, we need to understand the physics of bond dissociation under
      force, the impact of experimental technique on the measurement of detachment
      force (bond strength), the consequences of complex interactions in macromolecular
      bonds, and effects of multiply-bonded attachments.

PMID- 11340055
TI  - Nmr probes of molecular dynamics: overview and comparison with other techniques.
AB  - NMR spin relaxation spectroscopy is a powerful approach for characterizing
      intramolecular and overall rotational motions in proteins. This review describes
      experimental methods for measuring laboratory frame spin relaxation rate
      constants by high-resolution solution-state NMR spectroscopy, together with
      theoretical approaches for interpreting spin relaxation data in order to quantify
      protein conformational dynamics on picosecond-nanosecond time scales. Recent
      applications of these techniques to proteins are surveyed, and investigations of
      the contribution of conformational chain entropy to protein function are
      highlighted. Insights into the dynamical properties of proteins obtained from NMR
      spin relaxation spectroscopy are compared with results derived from other
      experimental and theoretical techniques.

PMID- 11340056
TI  - Structure of proteins involved in synaptic vesicle fusion in neurons.
AB  - The fusion of vesicles with target membranes is controlled by a complex network
      of protein-protein and protein-lipid interactions. Structures of the SNARE
      complex, synaptotagmin III, nSec1, domains of the NSF chaperone and its adaptor
      SNAP, and Rab3 and some of its effectors provide the framework for developing
      molecular models of vesicle fusion and for designing experiments to test these
      models.

PMID- 11340057
TI  - Ab initio protein structure prediction: progress and prospects.
AB  - Considerable recent progress has been made in the field of ab initio protein
      structure prediction, as witnessed by the third Critical Assessment of Structure
      Prediction (CASP3). In spite of this progress, much work remains, for the field
      has yet to produce consistently reliable ab initio structure prediction
      protocols. In this work, we review the features of current ab initio protocols in
      an attempt to highlight the foundations of recent progress in the field and
      suggest promising directions for future work.

PMID- 11340058
TI  - Structural relationships among regulated and unregulated phosphorylases.
AB  - Species and tissue-specific isozymes of phosphorylase display differences in
      regulatory properties consistent with their distinct roles in particular
      organisms and tissues. In this review, we compare crystallographic structures of
      regulated and unregulated phosphorylases, including maltodextrin phosphorylase
      (MalP) from Escherichia coli, glycogen phosphorylase from yeast, and mammalian
      isozymes from muscle and liver tissues. Mutagenesis and functional studies
      supplement the structural work and provide insights into the structural basis for
      allosteric control mechanisms. MalP, a simple, unregulated enzyme, is contrasted
      with the more complicated yeast and mammalian phosphorylases that have evolved
      regulatory sites onto the basic catalytic architecture. The human liver and
      muscle isozymes show differences structurally in their means of invoking
      allosteric activation. Phosphorylation, though common to both the yeast and
      mammalian enzymes, occurs at different sites and activates the enzymes by
      surprisingly different mechanisms.

PMID- 11340059
TI  - Biomolecular simulations: recent developments in force fields, simulations of
      enzyme catalysis, protein-ligand, protein-protein, and protein-nucleic acid
      noncovalent interactions.
AB  - Computer modeling has been developed and widely applied in studying molecules of
      biological interest. The force field is the cornerstone of computer simulations,
      and many force fields have been developed and successfully applied in these
      simulations. Two interesting areas are (a) studying enzyme catalytic mechanisms
      using a combination of quantum mechanics and molecular mechanics, and (b)
      studying macromolecular dynamics and interactions using molecular dynamics (MD)
      and free energy (FE) calculation methods. Enzyme catalysis involves forming and
      breaking of covalent bonds and requires the use of quantum mechanics. Noncovalent
      interactions appear ubiquitously in biology, but here we confine ourselves to
      review only noncovalent interactions between protein and protein, protein and
      ligand, and protein and nucleic acids.

PMID- 11340060
TI  - Chaperonin-mediated protein folding.
AB  - Molecular chaperones are required to assist folding of a subset of proteins in
      Escherichia coli. We describe a conceptual framework for understanding how the
      GroEL-GroES system assists misfolded proteins to reach their native states. The
      architecture of GroEL consists of double toroids stacked back-to-back. However,
      most of the fundamentals of the GroEL action can be described in terms of the
      single ring. A key idea in our framework is that, with coordinated ATP hydrolysis
      and GroES binding, GroEL participates actively by repeatedly unfolding the
      substrate protein (SP), provided that it is trapped in one of the misfolded
      states. We conjecture that the unfolding of SP becomes possible because a
      stretching force is transmitted to the SP when the GroEL particle undergoes
      allosteric transitions. Force-induced unfolding of the SP puts it on a higher
      free-energy point in the multidimensional energy landscape from which the SP can
      either reach the native conformation with some probability or be trapped in one
      of the competing basins of attraction (i.e., the SP undergoes kinetic
      partitioning). The model shows, in a natural way, that the time scales in the
      dynamics of the allosteric transitions are intimately coupled to folding rates of
      the SP. Several scenarios for chaperonin-assisted folding emerge depending on the
      interplay of the time scales governing the cycle. Further refinement of this
      framework may be necessary because single molecule experiments indicate that
      there is a great dispersion in the time scales governing the dynamics of the
      chaperonin cycle.

PMID- 11340061
TI  - Interpreting the effects of small uncharged solutes on protein-folding
      equilibria.
AB  - Proteins are designed to function in environments crowded by cosolutes, but most
      studies of protein equilibria are conducted in dilute solution. While there is no
      doubt that crowding changes protein equilibria, interpretations of the changes
      remain controversial. This review combines experimental observations on the
      effect of small uncharged cosolutes (mostly sugars) on protein stability with a
      discussion of the thermodynamics of cosolute-induced nonideality and critical
      assessments of the most commonly applied interpretations. Despite the controversy
      surrounding the most appropriate manner for interpreting these effects of
      thermodynamic nonideality arising from the presence of small cosolutes,
      experimental advantage may still be taken of the ability of the cosolute effect
      to promote not only protein stabilization but also protein self-association and
      complex formation between dissimilar reactants. This phenomenon clearly has
      potential ramifications in the cell, where the crowded environment could well
      induce the same effects.

PMID- 11340062
TI  - Photosystem II: the solid structural era.
AB  - Understanding the precise role of photosystem II as an element of oxygenic
      photosynthesis requires knowledge of the molecular structure of this membrane
      protein complex. The past few years have been particularly exciting because the
      structural era of the plant photosystem II has begun. Although the atomic
      structure has yet to be determined, the map obtained at 6 A resolution by
      electron crystallography allows assignment of the key reaction center subunits
      with their associated pigment molecules. In the following, we first review the
      structural details that have recently emerged and then discuss the primary and
      secondary photochemical reaction pathways. Finally, in an attempt to establish
      the evolutionary link between the oxygenic and the anoxygenic photosynthesis, a
      framework structure common to all photosynthetic reaction centers has been
      defined, and the implications have been described.

PMID- 11340063
TI  - Binding of ligands and activation of transcription by nuclear receptors.
AB  - Nuclear receptors (NRs) form a superfamily of ligand-inducible transcription
      factors composed of several domains. Recent structural studies focused on domain
      E, which harbors the ligand-binding site and the ligand-dependent transcription
      activation function AF-2. Structures of single representatives in an increasing
      number of various complexes as well as new structures of further NRs addressed
      issues such as discrimination of ligands, superagonism, isotype specificity, and
      partial agonism. Until today, one unique transcriptionally active form of domain
      E was determined; however, divergent tertiary structures of apo-forms and
      transcriptionally inactive forms are known. Thus, recent results link the
      transformation of NRs upon ligand binding to principles of protein folding.
      Furthermore, the ensemble of NR structures, including those of DNA-binding
      domains, provides one of the foundations for the understanding of interactions
      with transcription intermediary factors up to the characterization of the link
      between NR complexes and the basal transcriptional machinery at the structural
      level.

PMID- 11340064
TI  - Protein folding theory: from lattice to all-atom models.
AB  - This review focuses on recent advances in understanding protein folding kinetics
      in the context of nucleation theory. We present basic concepts such as
      nucleation, folding nucleus, and transition state ensemble and then discuss
      recent advances and challenges in theoretical understanding of several key
      aspects of protein folding kinetics. We cover recent topology-based approaches as
      well as evolutionary studies and molecular dynamics approaches to determine
      protein folding nucleus and analyze other aspects of folding kinetics. Finally,
      we briefly discuss successful all-atom Monte-Carlo simulations of protein folding
      and conclude with a brief outlook for the future.

PMID- 11340065
TI  - Activation of LIM kinases by myotonic dystrophy kinase-related Cdc42-binding
      kinase alpha.
AB  - LIM kinases (LIMK1 and LIMK2) regulate actin cytoskeletal reorganization through
      cofilin phosphorylation downstream of distinct Rho family GTPases. Pak1 and ROCK,
      respectively, activate LIMK1 and LIMK2 downstream of Rac and Rho; however, an
      effector protein kinase for LIMKs downstream of Cdc42 remains to be defined. We
      now report evidence that LIMK1 and LIMK2 activities toward cofilin
      phosphorylation are stimulated in cells by the co-expression of myotonic
      dystrophy kinase-related Cdc42-binding kinase alpha (MRCKalpha), an effector
      protein kinase of Cdc42. In vitro, MRCKalpha phosphorylated the protein kinase
      domain of LIM kinases, and the site in LIMK2 phosphorylated by MRCKalpha proved
      to be threonine 505 within the activation segment. Expression of MRCKalpha
      induced phosphorylation of actin depolymerizing factor (ADF)/cofilin in cells,
      whereas MRCKalpha-induced ADF/cofilin phosphorylation was inhibited by the co
      expression with the protein kinase-deficient form of LIM kinases. These results
      indicate that MRCKalpha phosphorylates and activates LIM kinases downstream of
      Cdc42, which in turn regulates the actin cytoskeletal reorganization through the
      phosphorylation and inactivation of ADF/cofilin.

PMID- 11340066
TI  - Molecular basis of aberrant apical protein transport in an intestinal enzyme
      disorder.
AB  - The impaired sorting profile to the apical membrane of human intestinal sucrase
      isomaltase is the underlying cause in the pathogenesis of a novel phenotype of
      intestinal congenital sucrase-isomaltase deficiency. Molecular characterization
      of this novel phenotype reveals a point mutation in the coding region of the
      sucrase-isomaltase (SI) gene that results in an amino acid substitution of a
      glutamine by arginine at residue 117 of the isomaltase subunit. This substitution
      is located in a domain revealing features of a trefoil motif or a P-domain in
      immediate vicinity of the heavily O-glycosylated stalk domain. Expression of the
      mutant SI phenotype in epithelial Madin-Darby canine kidney cells reveals a
      randomly targeted SI protein to the apical and basolateral membranes confirming
      an exclusive role of the Q117R mutation in generating this phenotype. Unlike wild
      type SI, the mutant protein is completely extractable with Triton X-100 despite
      the presence of O-glycans that serve in the wild type protein as an apical
      sorting signal and are required for the association of SI with detergent
      insoluble lipid microdomains. Obviously the O-glycans are not adequately
      recognized in the context of the mutant SI, most likely due to altered folding of
      the P-domain that ultimately affects the access of the O-glycans to a putative
      sorting element.

PMID- 11340067
TI  - Functional organization of the GluR1 glutamate receptor promoter.
AB  - The GluR1 glutamate receptor subunit is expressed in most brain areas and plays a
      major role in excitatory synaptic transmission. We cloned and sequenced 5
      kilobase pairs of the rat GluR1 promoter and identified multiple transcriptional
      start sites between -295 and -202 (relative to the first ATG). Similar to other
      glutamate receptor subunit promoters, the GluR1 promoter lacks TATA and CAAT
      elements in that region but binds Sp1 proteins at two sites. Promoter activity of
      GluR1 fragments cloned into pGL3 was assessed by immunocytochemistry and by
      measuring luciferase activity after transfection into primary cultures of rat
      cortical neurons and glia. GluR1 promoter activity was stronger in neurons, with
      neuronal specificity appearing to reside mainly within the neuronal expression
      enhancing regions, -1395 to -743 and -253 to -48. The latter region contains 4
      sites that bound recombinant cAMP-response element-binding proteins and a glial
      silencing region between -253 and -202. In both neurons and glia, promoter
      activity was increased by a 64-base pair GA repeat upstream of the initiation
      sites and reduced by a 57-base pair region that contained an N box. In contrast
      to the GluR2 promoter the regulatory regions are mainly located outside of the
      GluR1 initiation region.

PMID- 11340068
TI  - BAG-1 is a novel cytoplasmic binding partner of the membrane form of heparin
      binding EGF-like growth factor: a unique role for proHB-EGF in cell survival
      regulation.
AB  - Several cell functions related to growth and survival regulation have been
      attributed specifically to the membrane form of heparin-binding EGF-like growth
      factor (proHB-EGF), rather than to the diffusible, processed HB-EGF isoform.
      These findings suggest the existence of a functional binding partner specifically
      for the membrane form of the growth factor. In this study we have identified the
      prosurvival cochaperone, BAG-1, as a protein that interacts with the cytoplasmic
      tail domain of proHB-EGF. Interaction between BAG-1 and the 24-amino acid proHB
      EGF cytoplasmic tail was initially identified in a yeast two-hybrid screen and
      was confirmed in mammalian cells. The proHB-EGF tail bound BAG-1 in an hsp70
      independent manner and within a 97-amino acid segment that includes the ubiquitin
      homology domain in BAG-1 but does not include the hsp70 binding site. Effects of
      BAG-1 and proHB-EGF co-expression were demonstrated in cell adhesion and cell
      survival assays and in quantitative assays of regulated secretion of soluble HB
      EGF. Because the BAG-1 binding site is not present on the mature, diffusible form
      of the growth factor, these findings suggest a new mechanism by which proHB-EGF,
      in isolation from the diffusible form, can mediate cell signaling events. In
      addition, because effects of BAG-1 on regulated secretion of soluble HB-EGF were
      also identified, this interaction has the potential to alter the signaling
      capabilities of both the membrane-anchored and the diffusible forms of the growth
      factor.

PMID- 11340069
TI  - Crystalline ligand transitions in lamprey hemoglobin. Structural evidence for the
      regulation of oxygen affinity.
AB  - The hemoglobins of the Sea Lamprey (Petromyzon marinus) exist in an equilibrium
      between low affinity oligomers, stabilized by proton binding, and higher affinity
      monomers, stabilized by oxygen binding. Recent crystallographic analysis revealed
      that dimerization is coupled with key changes at the ligand binding site with the
      distal histidine sterically restricting ligand binding in the deoxy dimer but
      with no significant structural rearrangements on the proximal side. These
      structural insights led to the hypothesis that oxygen affinity of lamprey
      hemoglobin is distally regulated. Here we present the 2.9-A crystal structure of
      deoxygenated lamprey hemoglobin in an orthorhombic crystal form along with the
      structure of these crystals exposed to carbon monoxide. The hexameric assemblage
      in this crystal form is very similar to those observed in the previous deoxy
      structure. Whereas the hydrogen bonding network and packing contacts formed in
      the dimeric interface of lamprey hemoglobin are largely unaffected by ligand
      binding, the binding of carbon monoxide induces the distal histidine to swing to
      positions that would preclude the formation of a stabilizing hydrogen bond with
      the bound ligand. These results suggest a dual role for the distal histidine and
      strongly support the hypothesis that ligand affinity in lamprey hemoglobin is
      distally regulated.

PMID- 11340070
TI  - Heat shock RNA polymerase (E sigma(32)) is involved in the transcription of mlc
      and crucial for induction of the Mlc regulon by glucose in Escherichia coli.
AB  - Mlc is a global regulator of carbohydrate metabolism. Recent studies have
      revealed that Mlc is depressed by protein-protein interaction with enzyme
      IICB(Glc), a glucose-specific permease, which is encoded by ptsG. The mlc gene
      has been previously known to be transcribed by two promoters, P1(+1) and P2(+13),
      and have a binding site of its own gene product at +16. However, the mechanism of
      transcriptional regulation of the gene has not yet been established. In vitro
      transcription assays of the mlc gene showed that P2 promoter could be recognized
      by RNA polymerase containing the heat shock sigma factor final sigma(32) (E
      sigma(32)) as well as E sigma(70), while P1 promoter is only recognized by E
      sigma(70). The cyclic AMP receptor protein and cyclic AMP complex (CRP.cAMP)
      increased expression from P2 but showed negative effect on transcription from P1
      by E sigma(70), although it had little effect on transcription from P2 by E
      sigma(32) in vitro. Purified Mlc repressed transcription from both promoters, but
      with different degrees of inhibition. In vivo transcription assays using wild
      type and mlc strains indicated that the level of mlc expression was modulated
      less than 2-fold by glucose in the medium with concerted action of CRP.cAMP and
      Mlc. A dramatic increase in mlc expression was observed upon heat shock or in
      cells overexpressing final sigma(32), confirming that E sigma(32) is involved in
      the expression of mlc. Induction of ptsG P1 and pts P0 transcription by glucose
      was also dependent on E sigma(32). These results indicate that E sigma(32) plays
      an important role in balancing the relative concentration of Mlc and EIICB(Glc)
      in response to availability of glucose in order to maintain inducibility of the
      Mlc regulon at high growth temperature.

PMID- 11340071
TI  - Sticky DNA, a self-associated complex formed at long GAA*TTC repeats in intron 1
      of the frataxin gene, inhibits transcription.
AB  - Friedreich's ataxia (FRDA) is an autosomal recessive neurodegenerative disease
      caused by the expansion of GAA.TTC repeats in the first intron of the frataxin
      (X25) gene. FRDA patients carrying two expanded GAA.TTC repeats show very low
      levels of mature frataxin mRNA and protein. A novel type of unusual DNA
      structure, sticky DNA, was previously found in the expanded GAA.TTC repeats from
      FRDA patients. To evaluate the effect of sticky DNA on transcription, in vitro
      transcription studies of (GAA.TTC)(n) repeats (where n = 9-150) were carried out
      using T7 or SP6 RNA polymerase. When a gel-isolated sticky DNA template was
      transcribed, the amount of full-length RNA synthesized was significantly reduced
      compared with the transcription of the linear template. Surprisingly,
      transcriptional inhibition was observed not only for the sticky DNA template but
      also another DNA molecule used as an internal control in an orientation
      independent manner. The molecular mechanism of transcriptional inhibition by
      sticky DNA was a sequestration of the RNA polymerases by direct binding to the
      complex DNA structure. Moreover, plasmids containing the (GAAGGA.TCCTTC)(65)
      repeat, which does not form sticky DNA, did not inhibit in vitro transcription,
      as expected. These results suggest that the role of sticky DNA in FRDA may be the
      sequestration of transcription factors.

PMID- 11340072
TI  - Photoaffinity labeling of mouse fibroblast enzymes by a base excision repair
      intermediate. Evidence for the role of poly(ADP-ribose) polymerase-1 in DNA
      repair.
AB  - To examine the interaction of mammalian base excision repair (BER) enzymes with
      DNA intermediates formed during BER, we used a novel photoaffinity labeling probe
      and mouse embryonic fibroblast cellular extracts. The probe was formed in situ,
      using an end-labeled oligonucleotide containing a synthetic abasic site; this
      site was incised by apurinic/apyrimidinic endonuclease creating a nick with 3'
      hydroxyl and 5'-reduced sugar phosphate groups at the margins, and then a dNMP
      carrying a photoreactive adduct was added to the 3'-hydroxyl group. With near-UV
      light (312 nm) exposure of the extract/probe mixture, six proteins were strongly
      labeled. Four of these include poly(ADP-ribose) polymerase-1 (PARP-1) and the BER
      participants flap endonuclease-1, DNA polymerase beta, and apurinic/apyrimidinic
      endonuclease. The amount of the probe cross-linked to PARP-1 was greater than
      that cross-linked to the other proteins. The specificity of PARP-1 labeling was
      examined using various competitor oligonucleotides and DNA probes with alternate
      structures. PARP-1 labeling was stronger with a DNA representing a BER
      intermediate than with a nick in double-stranded DNA. These results indicate that
      proteins interacting preferentially with a photoreactive BER intermediate can be
      selected from the crude cellular extract.

PMID- 11340073
TI  - Development of zinc finger domains for recognition of the 5'-ANN-3' family of DNA
      sequences and their use in the construction of artificial transcription factors.
AB  - In previous studies we have developed Cys(2)-His(2) zinc finger domains that
      specifically recognized each of the 16 5'-GNN-3' DNA target sequences and could
      be used to assemble six-finger proteins that bind 18-base pair DNA sequences
      (Beerli, R. R., Dreier, B., and Barbas, C. F., III (2000) Proc. Natl. Acad. Sci.
      U. S. A. 97, 1495--1500). Such proteins provide the basis for the construction of
      artificial transcription factors to study gene/function relationships in the post
      genomic era. Central to the universal application of this approach is the
      development of zinc finger domains that specifically recognize each of the 64
      possible DNA triplets. Here we describe the construction of a novel phage display
      library that enables the selection of zinc finger domains recognizing the 5'-ANN
      3' family of DNA sequences. Library selections provided domains that in most
      cases showed binding specificity for the 3-base pair target site that they were
      selected to bind. These zinc finger domains were used to construct 6-finger
      proteins that specifically bound their 18-base pair target site with affinities
      in the pm to low nm range. When fused to regulatory domains, these proteins
      containing various numbers of 5'-ANN-3' domains were capable of specific
      transcriptional regulation of a reporter gene and the endogenous human ERBB-2 and
      ERBB-3 genes. These results suggest that modular DNA recognition by zinc finger
      domains is not limited to the 5'-GNN-3' family of DNA sequences and can be
      extended to the 5'-ANN-3' family. The domains characterized in this work provide
      for the rapid construction of artificial transcription factors, thereby greatly
      increasing the number of sequences and genes that can be targeted by DNA-binding
      proteins built from pre-defined zinc finger domains.

PMID- 11340074
TI  - Mdm2 mutant defective in binding p300 promotes ubiquitination but not degradation
      of p53: evidence for the role of p300 in integrating ubiquitination and
      proteolysis.
AB  - Turnover of the p53 tumor suppressor protein is mediated by Mdm2 through the
      ubiquitin proteolysis pathway. p300, a co-activator for p53, also participates in
      this process by complexing with Mdm2. We now report that the mutant Mdm2,
      defective in p53 binding, does not promote p53 ubiquitination and degradation in
      vivo or inhibit p53 transcriptional activation. By contrast, the mutant Mdm2,
      defective in p300 binding, still retains its activity to promote p53
      ubiquitination and to inhibit p53 transcriptional activation but fails in
      promoting p53 degradation. We also show that both wild-type Mdm2 and the mutant
      Mdm2, defective in p300 binding, can promote the ubiquitination of cancer-derived
      p53 mutants, but only wild-type Mdm2 can cause their degradation. Furthermore,
      adenoviral oncoprotein, 12S.E.1A, but not its deletion mutant that lacks p300
      binding, was shown to decrease in vivo ubiquitination of mutant p53. Taken
      together, these results provide genetic evidence that p300 plays a pivotal role
      in the regulation of Mdm2-mediated p53 turnover by integrating the cellular
      ubiquitination and proteolytic processes.

PMID- 11340075
TI  - Cytoplasmic dynein intermediate chain phosphorylation regulates binding to
      dynactin.
AB  - Previously, we identified dynactin as a cargo receptor or adaptor for cytoplasmic
      dynein, mediated by an interaction between the dynein intermediate chain and
      p150(Glued). To test phosphorylation as a potential regulatory mechanism for this
      interaction, we analyzed cytoplasmic dynein by two-dimensional gel analysis and
      detected two intermediate chain variants, one of which was eliminated by
      phosphatase treatment. Overlay assays demonstrated that p150(Glued) bound
      dephosphorylated but not phosphorylated intermediate chains. We then subjected
      the purified cytoplasmic dynein intermediate chain to mass spectrometry and
      identified a single phosphorylated tryptic fragment corresponding to the
      p150(Glued)-binding domain. Fragmentation and retention time analysis mapped the
      phosphorylation site to serine 84. Site-directed mutants designed to mimic the
      dephosphorylated or phosphorylated intermediate chain disrupted both in vitro
      phosphorylation and in vivo phosphorylation of transfected proteins. Mutants
      mimicking the dephosphorylated form bound p150(Glued) in vitro and overexpression
      perturbed transport of dynein-dependent membranes. Mutants mimicking the
      phosphorylated form displayed diminished p150(Glued) binding in vitro and did not
      disrupt dynein-mediated transport when expressed in vivo. These findings
      represent the first mapping of an intermediate chain phosphorylation site and
      suggest that this phosphorylation plays an important role in regulating the
      binding of cytoplasmic dynein to dynactin.

PMID- 11340076
TI  - Expression and function of lysophosphatidic acid receptors in cultured rodent
      microglial cells.
AB  - Microglia are the resident tissue macrophages of the central nervous system. They
      are rapidly activated by a variety of insults; and recently, receptors linked to
      cytoplasmic Ca(2+) signals have been implicated in such events. One potential
      class of receptors are those recognizing lysophosphatidic acid (LPA). LPA is a
      phospholipid signaling molecule that has been shown to cause multiple cellular
      responses, including increases in cytoplasmic calcium. We examined whether any of
      the known LPA receptor genes (lp(A1)/Edg2, lp(A2)/Edg4, and lp(A3)/Edg7) are
      expressed by cultured mouse or rat microglia. Reverse transcriptase-polymerase
      chain reaction indicated that mouse microglia predominantly expressed the lp(A1)
      gene, whereas rat microglia predominantly expressed lp(A3). Although LPA induced
      increases in the cytoplasmic Ca(2+) concentration in both microglial
      preparations, the responses differed substantially. The Ca(2+) signal in rat
      microglia occurred primarily through Ca(2+) influx via the plasma membrane,
      whereas the Ca(2+) signal in mouse microglia was due to release from
      intracellular stores. Only at high concentrations was an additional influx
      component recruited. Additionally, LPA induced increased metabolic activity in
      mouse (but not rat) microglial cells. Our findings provide evidence for
      functional LPA receptors on microglia. Thus, LPA might play an important role as
      a mediator of microglial activation in response to central nervous system injury.

PMID- 11340077
TI  - Elk-1, C/EBPalpha, and Pit-1 confer an insulin-responsive phenotype on prolactin
      promoter expression in Chinese hamster ovary cells and define the factors
      required for insulin-increased transcription.
AB  - The transcription factor(s) that mediate insulin-increased gene transcription are
      not well defined. These studies use phenotypic conversion of Rat2 and Chinese
      hamster ovary (CHO) cells with transcription factors to identify components
      required for regulation of prolactin promoter activity and its control by
      insulin. The pituitary-derived GH4 cells contain all of the transcription factors
      required for insulin-increased prolactin-chloramphenicol acetyltransferase (CAT)
      expression while HeLa cells require only Pit-1, a pituitary-specific factor.
      However, Rat2 and CHO cells require additional factors. We had determined
      previously that the transcription factor that mediates insulin-increased
      prolactin gene expression was likely an Ets-related protein. Elk-1 and Sap-1 were
      the only Ets-related transcription factors tested as chimeras with LexA DNA
      binding domain that were able to mediate insulin-increased expression of a LexA
      CAT reporter plasmid. Elk-1 and Sap-1 are expressed in GH4 and HeLa cells but
      Rat2 and CHO cells express Sap-1, but not Elk-1. Expression of Elk-1 made Rat2
      cells (but not CHO cells) insulin responsive. C/EBPalpha also binds to the
      prolactin promoter at a sequence overlapping the binding site for Elk-1.
      Expression of both C/EBPalpha and Pit-1 in CHO cells is required for high basal
      transcription of prolactin-CAT. Expression of Elk-1 converts CHO cells into a
      phenotype in which prolactin gene expression is increased by insulin treatment.
      Finally, antisense mediated reduction of Elk-1 in GH4 cells decreased insulin
      increased prolactin gene expression and confirmed the requirement for Elk-1 for
      insulin-increased prolactin gene expression. Thus, both C/EBPalpha and Pit-1 were
      required for high basal transcription while insulin sensitivity required Elk-1.

PMID- 11340078
TI  - The intronless and TATA-less human TAF(II)55 gene contains a functional initiator
      and a downstream promoter element.
AB  - Human TAF(II)55 (hTAF(II)55) is a component of the multisubunit general
      transcription factor TFIID and has been shown to mediate the functions of many
      transcriptional activators via direct protein-protein interactions. To uncover
      the regulatory properties of the general transcription machinery, we have
      isolated the hTAF(II)55 gene and dissected the regulatory elements and the core
      promoter responsible for hTAF(II)55 gene expression. Surprisingly, the hTAF(II)55
      gene has a single uninterrupted open reading frame and is the only intronless
      general transcription factor identified so far. Its expression is driven by a
      TATA-less promoter that contains a functional initiator and a downstream promoter
      element, as illustrated by both transfection assays and mutational analyses.
      Moreover, this core promoter can mediate the activity of a transcriptional
      activator that is artificially recruited to the promoter in a heterologous
      context. Interestingly, in the promoter-proximal region there are multiple Sp1
      binding sites juxtaposed to a single AP2-binding site, indicating that Sp1 and
      AP2 may regulate the core promoter activity of the hTAF(II)55 gene. These
      findings indicate that a combinatorial regulation of a general transcription
      factor-encoding gene can be conferred by both ubiquitous and cell type-specific
      transcriptional regulators.

PMID- 11340079
TI  - FLASH coordinates NF-kappa B activity via TRAF2.
AB  - FLASH is a protein recently shown to interact with the death effector domain of
      caspase-8 and is likely to be a component of the death-inducing signaling complex
      in receptor-mediated apoptosis. Here we show that antisense oligonucleotide
      induced inhibition of FLASH expression abolished TNF-alpha-induced activation of
      NF-kappaB in HEK293 cells, as determined by luciferase reporter gene expression
      driven by a NF-kappaB responsive promoter. Conversely, overexpression of FLASH
      dose-dependently activated NF-kappaB, an effect suppressed by dominant negative
      mutants of TRAF2, NIK, and IKKalpha, and partially by those of TRAF5 and TRAF6.
      TRAF2 was co-immunoprecipitated with FLASH from the cell extracts of HEK293 cells
      or HeLa cells stably expressing exogenous FLASH (HeLa/HA-FLASH). Furthermore,
      serial deletion mapping demonstrated that a domain spanning the residues 856-1191
      of FLASH activated NF-kappaB as efficiently as the full-length and could directly
      bind to TRAF2 in vitro and in the transfected cells. Taken together, these
      results suggest that FLASH coordinates downstream NF-kappaB activity via a TRAF2
      dependent pathway in the TNF-alpha signaling.

PMID- 11340080
TI  - Reconstitution and molecular analysis of the hRad9-hHus1-hRad1 (9-1-1) DNA damage
      responsive checkpoint complex.
AB  - DNA damage activates cell cycle checkpoint signaling pathways that coordinate
      cell cycle arrest and DNA repair. Three of the proteins involved in checkpoint
      signaling, Rad1, Hus1, and Rad9, have been shown to interact by
      immunoprecipitation and yeast two-hybrid studies. However, it is not known how
      these proteins interact and assemble into a complex. In the present study we
      demonstrated that in human cells all the hRad9 and hHus1 and approximately one
      half of the cellular pool of hRad1 interacted as a stable, biochemically discrete
      complex, with an apparent molecular mass of 160 kDa. This complex was
      reconstituted by co-expression of all three recombinant proteins in a
      heterologous system, and the reconstituted complex exhibited identical
      chromatographic behavior as the endogenous complex. Interaction studies using
      differentially tagged proteins demonstrated that the proteins did not self
      multimerize. Rather, each protein had a binding site for the other two partners,
      with the N terminus of hRad9 interacting with hRad1, the N terminus of hRad1
      interacting with hHus1, and the N terminus of hHus1 interacting with the C
      terminus of hRad9's predicted PCNA-like region. Collectively, these analyses
      suggest a model of how these three proteins assemble to form a functional
      checkpoint complex, which we dubbed the 9-1-1 complex.

PMID- 11340081
TI  - Nck and phosphatidylinositol 4,5-bisphosphate synergistically activate actin
      polymerization through the N-WASP-Arp2/3 pathway.
AB  - The Wiskott-Aldrich syndrome protein (WASP) and its relative neural WASP (N-WASP)
      regulate the nucleation of actin filaments through their interaction with the
      Arp2/3 complex and are regulated in turn by binding to GTP-bound Cdc42 and
      phosphatidylinositol 4,5-bisphosphate. The Nck Src homology (SH) 2/3 adaptor
      binds via its SH3 domains to a proline-rich region on WASP and N-WASP and has
      been implicated in recruitment of these proteins to sites of tyrosine
      phosphorylation. We show here that Nck SH3 domains dramatically stimulate the
      rate of nucleation of actin filaments by purified N-WASP in the presence of
      Arp2/3 in vitro. All three Nck SH3 domains are required for maximal activation.
      Nck-stimulated actin nucleation by N-WASP.Arp2/3 complexes is further stimulated
      by phosphatidylinositol 4,5-bisphosphate, but not by GTP-Cdc42, suggesting that
      Nck and Cdc42 activate N-WASP by redundant mechanisms. These results suggest the
      existence of an Nck-dependent, Cdc42-independent mechanism to induce actin
      polymerization at tyrosine-phosphorylated Nck binding sites.

PMID- 11340082
TI  - Haptotactic migration induced by midkine. Involvement of protein-tyrosine
      phosphatase zeta. Mitogen-activated protein kinase, and phosphatidylinositol 3
      kinase.
AB  - Midkine, a heparin-binding growth factor, plays a critical role in cell migration
      causing suppression of neointima formation in midkine-deficient mice. Here we
      have determined the molecules essential for midkine-induced migration. Midkine
      induced haptotaxis of osteoblast-like cells, which was abrogated by the soluble
      form of midkine or pleiotrophin, a midkine-homologous protein. Chondroitin
      sulfate B, E, chondroitinase ABC, B, and orthovanadate, an inhibitor of protein
      tyrosine phosphatase, suppressed the migration. Supporting these data, the cells
      examined expressed PTPzeta, a receptor-type protein-tyrosine phosphatase that
      exhibits high affinity to both midkine and pleiotrophin and harbors chondroitin
      sulfate chains. Furthermore, strong synergism between midkine and platelet
      derived growth factor in migration was detected. The use of specific inhibitors
      demonstrated that mitogen-activated protein (MAP) kinase and protein-tyrosine
      phosphatase were involved in midkine-induced haptotaxis but not PDGF-induced
      chemotaxis, whereas phosphatidylinositol 3 (PI3)-kinase and protein kinase C were
      involved in both functions. Midkine activated both PI3-kinase and MAP kinases,
      the latter activation was blocked by a PI3-kinase inhibitor. Midkine further
      recruited PTPzeta and PI3-kinase. These results indicate that PTPzeta and
      concerted signaling involving PI3-kinase and MAP kinase are required for midkine
      induced migration and demonstrate for the first time the synergism between
      midkine and platelet-derived growth factor in cell migration.

PMID- 11340083
TI  - Glucose regulation of the acetyl-CoA carboxylase promoter PI in rat hepatocytes.
AB  - The rat acetyl-CoA carboxylase (ACC) alpha gene is transcribed from two
      promoters, denoted PI and PII, that direct regulated expression in a tissue
      specific manner. Induction of ACC, the rate-controlling enzyme of fatty acid
      biosynthesis, occurs in the liver in response to feeding of a high carbohydrate,
      low fat diet, conditions that favor enhanced lipogenesis. This induction is
      mainly due to increases in PI promoter activity. We have used primary cultured
      hepatocytes from the rat to investigate glucose regulation of ACC expression.
      Glucose and insulin synergistically activated expression of ACC mRNAs transcribed
      from the PI promoter with little or no effect on PII mRNAs. Glucose treatment
      stimulated PI promoter activity in transfection assays and a glucose-regulated
      element was identified (-126/-102), homologous to those previously described in
      other responsive genes, including l-type pyruvate kinase, S(14) and fatty acid
      synthase. Mutation of this element eliminated the response to glucose. This
      region of the ACC PI promoter was able to bind a liver nuclear factor designated
      ChoRF that interacts with other conserved glucose-regulated elements. This ACC PI
      element is also capable of conferring a strong response to glucose when linked to
      a heterologous promoter. We conclude that induction of ACC gene expression under
      lipogenic conditions in hepatocytes is mediated in part by the activation of a
      glucose-regulated transcription factor, ChoRF, which stimulates transcription
      from the PI promoter. Similar mechanisms operate on related genes permitting the
      coordinate induction of the lipogenic pathway.

PMID- 11340084
TI  - Rac1 mediates type I collagen-dependent MMP-2 activation. role in cell invasion
      across collagen barrier.
AB  - Cell migration and proteolysis are two essential processes during tumor invasion
      and metastasis. Matrix metalloproteinase (MMP)-2 (type IV collagenase; gelatinase
      A), is implicated in tumor metastasis as well as in primary tumor growth. The Rho
      family of small GTPases regulates the dynamics of actin cytoskeleton associated
      with cell motility. In this report, we provide evidence that Rac1, one member of
      Rho-related small GTPases, is a mediator of MMP-2 activation in HT1080
      fibrosarcoma cells cultured in three-dimensional collagen gel (3D-col) and that
      MMP-2 activation is required for Rac1-promoted cell invasion through collagen
      barrier. Stable expression of dominant negative (Rac1V12N17) and constitutively
      active Rac1 (Rac1V12), respectively, in HT1080 cells demonstrates that Rac1
      promoted cell invasiveness across type I collagen and collagen-dependent MMP-2
      activation. Active Rac1 is sufficient to induce MMP-2 activation in cells
      cultured in fibrin gel, an extracellular matrix component that does not support
      MMP-2 activation. The Rac1-dependent MMP-2 activation occurred in a cell
      associated fashion and required MMP activities. Because the cell membrane
      mediated MMP-2 activation requires MT1-MMP and low amount of issue inhibitor of
      matrix metalloproteinase-2 (TIMP-2), their expression was examined. Rac1
      modulated MT1-MMP mRNA level and the accumulation of a 43-kDa form of MT1-MMP
      protein, in correlation with MMP-2 activation profile. However, TIMP-2 expression
      was independent of Rac1 activity. The coordinate modulation of MMP-2 activity and
      MT1-MMP expression/processing by Rac1 is consistent with cell collagenolytic
      activity. The C-terminal hemopexin-like domain of MMP-2, which interferes with
      the cell membrane activation of MMP-2, reduced Rac1-promoted cell invasiveness as
      monitored by collagen invasion assay. These results suggest that collagen
      dependent MMP-2 activation and MT1-MMP expression/processing contribute to Rac
      promoted tumor cell invasion through interstitial collagen barrier.

PMID- 11340085
TI  - p300 coactivates the adipogenic transcription factor CCAAT/enhancer-binding
      protein alpha.
AB  - Despite the knowledge that CCAAT/enhancer-binding protein alpha (C/EBPalpha)
      plays an important role in preadipocyte differentiation, our understanding of how
      C/EBPalpha interacts with nuclear proteins to regulate transcription is limited.
      Based on the hypothesis that evolutionarily conserved regions are functionally
      important and likely to interact with coactivators, we compared the amino acid
      sequence of C/EBPalpha from different species (frog to human) and identified four
      highly conserved regions (CR1-CR4) within the transactivation domain. A series of
      amino-terminal truncations and internal deletion constructs were made creating
      forms of C/EBPalpha which lack single or multiple conserved regions. To determine
      which regions of the C/EBPalpha transactivation domain are important in its
      ability to induce spontaneous differentiation of 3T3-L1 preadipocytes, we
      infected preadipocytes with expression vectors encoding the C/EBPalpha conserved
      region mutants and observed their ability to induce differentiation. We found
      that CR2 fused to the DNA binding domain is able to induce spontaneous
      differentiation independent of the other conserved regions. However, CR2 was not
      necessary for the adipogenic action of C/EBPalpha because a combination of CR1
      and CR3 can also induce adipogenesis. Because the transcriptional coactivator
      p300 participates in the signaling of many transcription factors to the basal
      transcriptional apparatus, we examined whether functional interaction exists
      between C/EBPalpha and p300. Cotransfection of p300 with p42C/EBPalpha results in
      a synergistic increase in leptin promoter activity, indicating that p300 acts as
      a transcriptional coactivator of C/EBPalpha. Analyses using C/EBPalpha conserved
      region mutants suggest that multiple regions (CR2 and CR3) of the C/EBPalpha
      transactivation domain functionally interact with p300.

PMID- 11340086
TI  - Reciprocal phosphorylation and regulation of endothelial nitric-oxide synthase in
      response to bradykinin stimulation.
AB  - Endothelial nitric-oxide synthase (eNOS) is phosphorylated at Ser-1179 (bovine
      sequence) by Akt after growth factor or shear stress stimulation of endothelial
      cells, resulting in increased eNOS activity. Purified eNOS is also phosphorylated
      at Thr-497 by purified AMP-activated protein kinase, resulting in decreased eNOS
      activity. We investigated whether bradykinin (BK) stimulation of bovine aortic
      endothelial cells (BAECs) regulates eNOS through Akt activation and Ser-1179 or
      Thr-497 phosphorylation. Akt is transiently activated in BK-stimulated BAECs.
      Activation is blocked completely by wortmannin and LY294002, inhibitors of
      phosphatidylinositol 3-kinase, suggesting that Akt activation occurs downstream
      from phosphatidylinositol 3-kinase. BK stimulates a transient phosphorylation of
      eNOS at Ser-1179 that is correlated temporally with a transient dephosphorylation
      of eNOS at Thr-497. Phosphorylation at Ser-1179, but not dephosphorylation at Thr
      497, is blocked by wortmannin and LY294002. BK also stimulates a transient nitric
      oxide (NO) release from BAECs with a time-course similar to Ser-1179
      phosphorylation and Thr-497 dephosphorylation. NO release is not altered by
      wortmannin. BK-stimulated dephosphorylation of Thr-497 and NO release are blocked
      by the calcineurin inhibitor, cyclosporin A. These data suggest that BK
      activation of eNOS in BAECs primarily involves deinhibition of the enzyme through
      calcineurin-mediated dephosphorylation at Thr-497.

PMID- 11340089
TI  - Alcohol, red wine and cardiovascular disease.
AB  - The objective of this article is to review the existing literature concerning the
      effects and mechanisms of action of red wine consumption vs. other alcoholic
      beverages on the risk of cardiovascular disease (CVD). Of particular interest is
      the form and quantity of alcohol consumed. This relationship between alcohol
      consumption and mortality is well supported by epidemiologic studies, which have
      suggested that different forms of alcohol alter the relative risk values for
      mortality from CVD. Although not without exception, current evidence from
      epidemiologic and experimental studies suggests a protective effect against the
      development of CVD with moderate consumption of red wine. The exact nature of the
      protective effect remains to be established. However, mechanisms including LDL
      oxidation and alterations in hemostatic variables are being increasingly
      recognized as contributory. Key components of red wine thought to be responsible
      for the protective effects include phenolic compounds and alcohol content.
      Despite the research presented, some questions relating to the current
      recommendations regarding moderate alcohol consumption and cardiovascular health
      remain. However, collectively, the literature aids in understanding some of the
      ways in which alcoholic beverages and their components affect the health of our
      population.

PMID- 11340090
TI  - Mechanisms involved in the intestinal digestion and absorption of dietary vitamin
      A.
AB  - Dietary retinyl esters are hydrolyzed in the intestine by the pancreatic enzyme,
      pancreatic triglyceride lipase (PTL), and intestinal brush border enzyme,
      phospholipase B. Recent work on the carboxylester lipase (CEL) knockout mouse
      suggests that CEL may not be involved in dietary retinyl ester digestion. The
      possible roles of the pancreatic lipase-related proteins (PLRP) 1 and 2 and other
      enzymes require further investigation. Unesterified retinol is taken up by the
      enterocytes, perhaps involving both diffusion and protein-mediated facilitated
      transport. Once in the cell, retinol is complexed with cellular retinol-binding
      protein type 2 (CRBP2) and the complex serves as a substrate for reesterification
      of the retinol by the enzyme lecithin:retinol acyltransferase (LRAT). Retinol not
      bound to CRBP2 is esterified by acyl-CoA acyltransferase (ARAT). The retinyl
      esters are incorporated into chylomicrons, intestinal lipoproteins that transport
      other dietary lipids such as triglycerides, phospholipids, and cholesterol.
      Chylomicrons containing newly absorbed retinyl esters are then secreted into the
      lymph.

PMID- 11340091
TI  - Isolation of an antitumor compound from Agaricus blazei Murill and its mechanism
      of action.
AB  - The Basidiomycete fungus Agaricus blazei Murill has traditionally been used as a
      health food for the prevention of cancer, diabetes, hyperlipidemia,
      arteriosclerosis and chronic hepatitis. In the present study, we examined the
      antitumor activities of various substances isolated from the lipid fraction of A.
      blazei. Tumor growth was retarded by the oral administration of the lipid
      fraction extracted from A. blazei with a chloroform/methanol mixture in sarcoma
      180-bearing mice. The substance with the antitumor activity in the lipid fraction
      was isolated via silica gel column chromatography, eluted with an
      acetonitrile/methanol (3:2) mixture and identified as ergosterol by direct
      comparison of the (1)H NMR and mass spectrometry spectral data of an authentic
      sample. The oral administration of ergosterol to sarcoma 180-bearing mice
      significantly reduced tumor growth at doses of 400 and 800 mg/kg administered for
      20 d without side effects, such as the decreases in body, epididymal adipose
      tissue, thymus, and spleen weights and leukocyte numbers induced by cancer
      chemotherapy drugs. Ergosterol had no cytotoxicity against tumor cells. To
      clarify the antitumor activity of ergosterol, we examined the effects of
      ergosterol on tumor-induced angiogenesis using two in vivo models.
      Intraperitoneal administration of ergosterol at doses of 5, 10 and 20 mg/kg for 5
      consecutive d inhibited the neovascularization induced by Lewis lung carcinoma
      cell-packed chambers, suggesting that either ergosterol or its metabolites may be
      involved in the inhibition of tumor-induced neovascularization. Therefore, we
      further examined the inhibitory effects of ergosterol on Matrigel-induced
      neovascularization. Female C57BL/6 mice were subcutaneously inoculated with
      Matrigel containing acidic fibroblast growth factor and heparin with or without
      ergosterol. Ergosterol inhibited the Matrigel-induced neovascularization,
      suggesting that ergosterol directly inhibits Matrigel-induced neovascularization.
      From these results, it seems likely that the antitumor activity of ergosterol
      might be due to direct inhibition of angiogenesis induced by solid tumors. This
      is the first report of ergosterol as an antiangiogenic substance.

PMID- 11340092
TI  - Zinc has an insulin-like effect on glucose transport mediated by phosphoinositol
      3-kinase and Akt in 3T3-L1 fibroblasts and adipocytes.
AB  - Zinc has insulin-like effects on cells, including promotion of both lipogenesis
      and glucose transport. The relationship between zinc and the stimulation of
      glucose transport is unclear. We hypothesize that zinc affects the insulin
      signaling pathway. In this study, the effect of zinc on glucose transport and
      insulin signaling was examined in 3T3-L1-preadipocytes and -adipocytes. Treatment
      of cells with up to 200 micromol/L zinc significantly increased glucose transport
      (P < 0.05). The effect of zinc on adipocytes was greater than on preadipocytes,
      and the effect of zinc plus insulin was greater than that of either insulin or
      zinc alone. Cytochalasin D, which disrupts actin filaments, attenuated the
      increase of glucose transport induced by zinc or insulin (P < 0.05). At 100
      nmol/L, wortmannin, the phosphoinositide (PI) 3-kinase inhibitor, decreased basal
      glucose transport and blocked zinc-stimulated glucose transport in both cell
      types (P < 0.05). H7, an inhibitor of protein kinase C, did not reduce basal
      glucose transport but decreased zinc-induced glucose transport (P < 0.05). Zinc
      increased tyrosine phosphorylation of the insulin receptor beta subunit of both
      preadipocytes and adipocytes after 5-10 min of treatment (P < 0.05). Zinc at 200
      micromol/L did not affect tyrosine phosphorylation of insulin receptor substrate
      (IRS)-1 or -2; further, there was no effect of zinc on the association of the p85
      subunit of PI 3-kinase and IRS-1. Zinc significantly increased serine-473
      phosphorylation of Akt in both preadipocytes and adipocytes (P < 0.05). The PI 3
      kinase inhibitor, wortmannin, totally blocked the effect of zinc on Akt
      activation. Hence, it appears that zinc can induce an increase in glucose
      transport into cells and potentiate insulin-induced glucose transport, likely
      acting through the insulin-signaling pathway.

PMID- 11340093
TI  - Red and black rice decrease atherosclerotic plaque formation and increase
      antioxidant status in rabbits.
AB  - The influence of white, red and black rice consumption on atherosclerotic plaque
      formation induced by hypercholesterolemia was investigated in rabbits. Male
      rabbits (n = 36) were divided into five groups. They were fed a normal laboratory
      purified diet (normal group, n = 6), a high cholesterol (0.5 g/100 g) diet (HC
      group, n = 6), a high cholesterol diet with 30 g/100 g white rice (WR group, n =
      8), 30 g/100 g red rice (RR group, n = 8), or 30 g/100 g black rice (BR group, n
      = 8) for 10 wk. Blood samples were collected for lipid measurements and aorta
      were removed for assessment of atherosclerotic plaques at the end of the
      protocol. The oxidant and antioxidant status of blood, erythrocytes, liver and
      aorta was evaluated. The area of atherosclerotic plaque was 50% lower in rabbits
      fed the red or black rice diets than in those fed the white rice diet. Compared
      with the HC and WR groups, serum HDL cholesterol and apolipoprotein (apo) A-I
      concentration were greater (P < 0.05) in the RR and BR groups. Liver reactive
      oxygen species (ROS) and aortic malondialdehyde (MDA) were significantly lower,
      and the liver total antioxidative capacity (TAC) and erythrocyte superoxide
      dismutase (SOD) activity were significantly higher in the RR and BR groups
      compared with the HC and WR groups. Red or black rice consumption reduced or
      retarded the progression of atherosclerotic plaque development induced by dietary
      cholesterol. The enhanced serum HDL cholesterol and apo A-I concentrations, and
      the increased antioxidant and decreased oxidative status may be mechanisms of the
      antiatherogenic effect of red or black rice.

PMID- 11340094
TI  - Tumor suppressor protein p53 mRNA and subcellular localization are altered by
      changes in cellular copper in human Hep G2 cells.
AB  - Copper toxicity causes hepatic damage that can lead to the development of
      hepatocarcinoma. Similarly, copper deficiency has been reported to increase
      hepatocyte tumorigenesis. Thus, the objective of this work was to explore the
      role of copper toxicity and deficiency in the regulation of the tumor suppressor
      protein p53. Using Northern analysis, Western analysis, immunocytochemistry and
      the human hepatoma cell line Hep G2, this work showed that elevations in
      hepatocyte copper consistent with Wilson's disease (5.7-fold increase) induced
      p53 mRNA and confirmed that copper toxicity is correlated with apoptotic cell
      death. However, Western analysis and immunocytochemistry showed that post
      transcriptional mechanisms are a significant part of the process, with p53
      translocation from the cytosol into the nucleus of copper-treated cells.
      Treatment of Hep G2 cells with increasing concentrations of the copper chelator
      tetraethylenepentamine (TEPA, 0-50 micromol/L, 48 h) reduced cellular copper and
      increased mean p53 mRNA abundance by over fourfold with nuclear translocation of
      the wild-type protein. However, TEPA treatment did not result in a loss of cell
      viability or appear to induce apoptosis.

PMID- 11340095
TI  - Alanyl-glutamine dipeptide does not affect hemodynamics despite a greater
      increase in myocardial heat shock protein 72 immunoreactivity in endotoxemic
      sheep.
AB  - The possible beneficial effect of supplemental glutamine (Gln) in critically ill
      patients has been suggested to be mediated by the induction of the cytoprotective
      heat shock proteins (HSP)32 and HSP72. There is evidence that HSP72 and HSP32
      have opposite effects on the hemodynamic situation during endotoxemia. Therefore,
      the effect of Gln supplementation on the cardiovascular system is not clear. We
      investigated the effect of alanyl-Gln (Ala-Gln) dipeptide on cardiovascular
      function in healthy and endotoxemic sheep. Ten sheep catheterized for chronic
      studies received Ala-Gln 700 mg/(kg x d) [equal to 470 mg/(kg x d)Gln] on 4
      consecutive days, and 10 sheep received NaCl (9 g/L) as the control solution. On
      d 4, four sheep of each group were killed and myocardial samples were taken for
      immunohistochemistry. The remaining sheep received a continuous infusion of
      endotoxin [Salmonella typhosa, 10 ng/(kg x min)]. Hemodynamic parameters were
      measured before application of Ala-Gln or the control solution, and during
      endotoxemia. Myocardial HSP72 immunoreactivity was determined by
      immunohistochemistry. After 24 h of endotoxemia, the sheep exhibited a
      hyperdynamic circulation. No difference was found in the hemodynamic parameters
      between treatment and control group. Ala-Gln treated sheep had a greater increase
      in myocardial HSP72 immunoreactivity compared with controls after (P < 0.05) but
      not before endotoxemia. In summary, Ala-Gln increased HSP72 immunoreactivity
      after endotoxemia, but did not alter hemodynamic parameters. Thus, Ala-Gln
      supplementation does not seem to aggravate the hyperdynamic circulation in
      endotoxemic shock.

PMID- 11340096
TI  - Dietary fat and garlic oil independently regulate hepatic cytochrome p(450) 2B1
      and the placental form of glutathione S-transferase expression in rats.
AB  - The individual and combined effects of dietary fat and garlic oil on two drug
      metabolizing enzymes, cytochrome P(450) 2B1 and the placental form of glutathione
      (GSH) S-transferase (PGST), in rat liver were examined in this study. Rats were
      fed a low corn oil, high corn oil or high fish oil diet and received various
      amount of garlic oil (0, 30, 80, 200 mg/kg body) orally three times per week for
      6 wk. The fat energy in the low and high fat diets accounted for 11.6 and 45.7%
      of total energy, respectively. Final body weights did not differ among the three
      dietary fat groups and were not affected by garlic oil treatment. The fatty acid
      profile in hepatic phospholipids revealed higher eicosapentaenoic acid [20:5(n
      3)] and docosahexaenoic acid [22:6(n-3)] levels in the fish oil-fed group than in
      the low and high corn oil-fed groups (P < 0.05). In contrast, the corn oil-fed
      groups had greater hepatic phospholipid arachidonic acid [20:4(n-6)] levels (P <
      0.05). Both dietary fat and garlic oil significantly affected hepatic cytochrome
      7-pentoxyresorufin O-dealkylase (PROD) activity and GST activity toward
      ethacrynic acid. Rats fed the high fish oil diet had 85 and 51% higher PROD
      activity compared with those fed the low or the high corn oil diet, respectively
      (P < 0.05). The GST activity in the high fish oil and the high corn oil groups
      was 33 and 18% higher than that in the low corn oil group (P < 0.05),
      respectively, and the GST activity in rats fed the high fish oil diet was higher
      than in those fed the high corn oil diet (P < 0.05). Garlic oil dose-dependently
      increased GST activity. No interaction between dietary fat and garlic oil on PROD
      or GST activity was noted. Northern and Western blot analysis revealed that
      dietary fish oil increased both cytochrome P(450) 2B1 and PGST mRNA and protein
      levels. Cytochrome P(450) 2B1 and PGST mRNA and protein levels were also dose
      dependently increased by garlic oil treatment. The effects of garlic oil and
      dietary fat on P(450) 2B1 and PGST mRNA and protein expression were independent.
      These results indicate that dietary fat and garlic oil independently modulate
      P(450) 2B1 and PGST expression at transcriptional and/or post-transcriptional
      stages.

PMID- 11340097
TI  - Postpubertal development of the rat mammary gland is preserved during iron
      deficiency.
AB  - We previously showed that moderate iron deficiency is associated with increased
      susceptibility to chemically induced breast carcinogenesis. Epidemiological and
      experimental data suggest that breast cancer risk may be modulated by the
      developmental and proliferative state of the mammary epithelium. The adverse
      effects of iron deficiency on organ growth are well documented. However, the role
      of iron in mammary gland development has not been examined. Therefore, we studied
      the effect of iron deficiency on mammary gland development and epithelial cell
      kinetics in female Sprague-Dawley rats. Weanling rats were fed experimental diets
      that provide 6 (severe), 12 (moderate) or 35 (control) mg Fe/kg diet. After 6 wk
      of treatment, hematocrit and blood hemoglobin were lower in iron-restricted rats
      than in controls, with significant differences from controls observed in rats
      receiving 6 mg Fe/kg diet (P < 0.05). Liver iron was reduced 90 and 80% in severe
      and moderate groups, respectively, compared with controls. Puberty onset and 17
      beta-estradiol levels were unaltered by iron status, but plasma progesterone was
      significantly lower in iron-restricted groups (P < 0.05). Microscopic examination
      of mammary gland whole mounts revealed an increased density of terminal end buds
      in thoracic glands from iron-restricted rats, indicative of decreased
      differentiation, although the differences were not statistically significant
      compared with controls (P = 0.21). Mammary epithelial cell proliferation,
      determined in contralateral glands by measuring 5-bromo-2'-deoxyuridine
      incorporation, did not differ between rats receiving 12 and 35 mg Fe/kg diet. In
      conclusion, these results suggest that alveolar development of the mammary gland
      and the proliferative capacity of the mammary epithelium are refractory to iron
      deficiency during early postpubertal growth of the rat.

PMID- 11340098
TI  - Dietary tomato paste protects against ultraviolet light-induced erythema in
      humans.
AB  - Carotenoids are efficient antioxidants capable of scavenging reactive oxygen
      species generated under conditions of photooxidative stress. It has been shown
      that supplementation with high doses of beta-carotene protects skin against UV
      induced erythema. This study was designed to investigate whether intervention
      with a natural dietary source rich in lycopene protects against UV-induced
      erythema in humans. Tomato paste (40 g), providing approximately 16 mg/d of
      lycopene, was ingested with 10 g of olive oil over a period of 10 wk by 9
      volunteers. Controls (n = 10) received olive oil only. Erythema was induced by
      illumination of dorsal skin (scapular region) with a solar simulator at the
      beginning of the study, after 4 wk and after 10 wk. Intensity of erythema was
      measured by chromatometry; the a-value was determined directly before and 24 h
      after irradiation. Serum carotenoid levels were measured by HPLC. At the
      beginning of the study, carotenoid levels did not differ between the two groups.
      Serum levels of lycopene increased in supplemented subjects; the other
      carotenoids did not change significantly, and no change in serum carotenoids was
      observed in the control group. At wk 10, dorsal erythema formation was 40% lower
      in the group that consumed tomato paste compared with controls (P = 0.02;
      Wilcoxon-Mann-Whitney test). No significant difference between groups was found
      at wk 4 of treatment. The data demonstrate that it is feasible to achieve
      protection against UV light-induced erythema by ingestion of a commonly consumed
      dietary source of lycopene.

PMID- 11340099
TI  - Elevated iron status increases bacterial invasion and survival and alters
      cytokine/chemokine mRNA expression in Caco-2 human intestinal cells.
AB  - Iron status affects both microbial growth and immune function. Mammalian iron
      homeostasis is maintained primarily by regulating the absorption of the
      micronutrient in the proximal small intestine. The iron concentration of the
      enterocyte can fluctuate widely in response to both dietary and whole body iron
      status, as well as in response to infections. The possibility that an enterocyte
      with an elevated iron concentration is more susceptible to invasion by enteric
      pathogens is not known. Therefore, we examined the impact of enterocyte iron
      status on the invasion and survival of an enteric pathogen, as well as on the
      levels of several cytokine and chemokine mRNAs by the host cell. The enterocyte
      like Caco-2 human intestinal cell line and Salmonella enteritidis served as the
      models to examine the effect of iron on the host-parasite interaction. Iron
      status of Caco-2 cells was altered by incubation in serum-free medium
      supplemented with varying levels of iron. Elevated iron status of Caco-2 cells
      increased the efficiency of the invasion and the number of bacteria surviving in
      the intracellular environment. Caco-2 cells constitutively expressed transforming
      growth factor-beta1, interleukin-8, monocyte chemotactic protein-1, tumor
      necrosis factor-alpha and interleukin-1beta, and infection with S. enteritidis
      increased the relative quantities of all cytokine/chemokine mRNAs except
      interleukin-1beta. Elevated iron status of Caco-2 cells decreased the levels of
      cytokine/chemokine mRNAs by 25-45% in uninfected cells. In contrast, bacterial
      infection was associated with a 21-95% increase in cytokine/chemokine mRNAs
      levels in Caco-2 cells with higher iron concentration compared with infected
      cells with lower iron concentration. These data support the hypothesis that
      elevated enterocyte iron status increases susceptibility to infection and
      exacerbates the mucosal inflammatory response initiated by microbial invasion by
      increasing cytokine/chemokine expression.

PMID- 11340100
TI  - Expression of stimulator of Fe transport is not enhanced in Hfe knockout mice.
AB  - Hfe knockout (-/-) mice recapitulate many of the biochemical abnormalities of
      hereditary hemochromatosis (HH), but the molecular mechanisms involved in the
      etiology of iron overload in HH remain poorly understood. It was found previously
      that livers of patients with HH contained 5-fold higher SFT (stimulator of Fe
      transport) mRNA levels relative to subjects without HH. Because this observation
      suggests a possible role for SFT in HH, we investigated SFT mRNA expression in
      Hfe(-/-) mice. The 4- and 10-wk-old Hfe(-/-) mice do not have elevated levels of
      hepatic SFT transcripts relative to age-matched Hfe(+/+) mice, despite having 2.2
      and 3.3-fold greater hepatic nonheme iron concentrations, respectively. Northern
      blot analyses of various mouse tissues revealed that SFT is widely expressed. The
      novel observation that SFT transcripts are abundant in brain prompted a
      comparison of SFT transcript levels and nonheme iron levels in the brains of
      Hfe(+/+) and Hfe(-/-) mice. Neither SFT mRNA levels nor nonheme iron levels
      differed between groups. Further comparisons of Hfe(-/-) and Hfe(+/+) mouse
      tissues revealed no significant differences in SFT mRNA levels in duodenum, the
      site of increased iron absorption in HH. Important distinctions between Hfe(-/-)
      mice and HH patients include not only differences in the relative rate and
      magnitude of iron loading but also the lack of fibrosis and phlebotomy treatment
      in the knockout animals.

PMID- 11340101
TI  - An oat-containing hypocaloric diet reduces systolic blood pressure and improves
      lipid profile beyond effects of weight loss in men and women.
AB  - Hypertension, dyslipidemia and overweight contribute substantially to
      cardiovascular disease risk. One of the most effective methods for improving high
      blood pressure and lipid profiles is loss of excess weight. Other recommendations
      for reducing cardiovascular risk include changes in dietary micronutrient,
      macronutrient and fiber intakes. To better define a diet for reduction in
      cardiovascular risk, 43 adults (body mass index 26.4 +/- 3.3, range 20.5-33.9
      kg/m(2)) participated in an 8-wk study to determine the effects of two diets on
      weight, blood pressure, lipids and insulin sensitivity. For 2 wk, weight was
      maintained and all subjects consumed a control diet. For the next 6 wk, subjects
      consumed one of two hypocaloric diets (maintenance energy minus 4.2 MJ/d): the
      control diet (n = 21) or a diet containing oats [45 g/(4.2 MJ dietary energy. d),
      n = 22]. There was no significant difference between groups in changes in weight
      loss (control -4.0 +/- 1.1 kg, oats -3.9 +/- 1.6 kg, P = 0.8). The oats diet
      resulted in greater decreases in mean systolic blood pressure (oats -6 +/- 7 mm
      Hg, control -1 +/- 10 mm Hg, P = 0.026), whereas diastolic blood pressure change
      did not differ between the two groups (oats -4 +/- 6 mm Hg, control -3 +/- 5 mm
      Hg, P = 0.8). The oat diet resulted in significantly greater decreases in total
      cholesterol (oats -0.87 +/- 0.47 mmol/L, control -0.34 +/- 0.5 mmol/L, P = 0.003)
      and LDL cholesterol (oats -0.6 +/- 0.41 mmol/L, control -0.2 +/- 0.41mmol/L, P =
      0.008). In summary, a hypocaloric diet containing oats consumed over 6 wk
      resulted in greater improvements in systolic blood pressure and lipid profile
      than did a hypocaloric diet without oats.

PMID- 11340102
TI  - Gender may affect the action of garlic oil on plasma cholesterol and glucose
      levels of normal subjects.
AB  - Early trials of garlic preparations on blood lipids mainly supported a lipid
      lowering effect, whereas later well-designed garlic tablet trials were mainly
      entirely null. However, enteric simulation tests suggest that this discordance
      may result from ineffective delivery of bioactive agents from the brands of
      garlic powder (GP) and cyclodextrin-bound garlic oil (GO) tablets tested in some
      recent negative trials. In contrast, enteric simulation tests show that the
      preformed bioactive agents present in "traditional" gelatin capsules of GO are
      efficiently released, although such capsules have rarely been investigated in
      lipid-lowering trials. It was hypothesized that gelatin capsules of GO given to
      normal subjects would improve specified coronary heart disease risk factors.
      Effects of a GP preparation were also investigated. Subjects (n = 51; men and
      women, mean age 27 y) were randomly assigned to receive either 8.2 mg/d of GO
      (allyl sulfides) or placebo for 11 wk. Another 27 subjects received garlic powder
      (GP) of similar biopotential (7.8 mg allicin/d). Outcome measures were 95%
      confidence intervals (CI) between GO and placebo groups for differences between
      baseline and subsequent sample times. Men and women combined showed no
      significant differences save for an improved total antioxidant capacity at 6 wk
      (P = 0.01). Hence, no benefit from GO after 11 wk is one plausible conclusion.
      However, there were significant differences in effect of GO between men and women
      for HDL cholesterol (HDL-C) (P = 0.004) and total cholesterol (TC)/HDL-C (P =
      0.003). Women showed favorable effects in terms of CHD risk factors (i.e.,
      increases in HDL-C and reductions in TC/HDL-C), whereas men had small adverse
      effects. There was a significant difference in the GO effect for glucose (P =
      0.006), with a reduction seen for men and an increase for women. The gender
      effects were unexpected and such analyses were not planned in advance.
      Confirmation of these findings with larger numbers of subjects would have
      importance for the use of garlic against CHD and for the design of future garlic
      studies.

PMID- 11340103
TI  - In vivo biotin supplementation at a pharmacologic dose decreases proliferation
      rates of human peripheral blood mononuclear cells and cytokine release.
AB  - Theoretically, vitamin supplements may either enhance or reduce protein synthesis
      and proliferation in peripheral blood mononuclear cells (PBMC). In the present
      study, we determined whether administration of a pharmacologic dose of biotin
      affects proliferation rates of PBMC and cytokine release. Healthy adults (n = 5)
      ingested 3.1 micromol biotin/d for 14 d; blood and urine were collected pre- and
      postsupplementation. PBMC were isolated by density gradient and incubated with
      the mitogen concanavalin A for up to 3 d. At timed intervals during mitogen
      stimulation, we measured the following: 1) cellular uptake of [(3)H]thymidine to
      determine proliferation rates; 2) concentrations of various cytokines released
      into the medium; and 3) the percentages of PBMC subsets as judged by CD surface
      markers. Biotin supplementation caused a significant decrease of PBMC
      proliferation. At 2 d after mitogen stimulation, [(3)H]thymidine uptake by
      postsupplementation PBMC was 66 +/- 21% of the uptake by presupplementation PBMC
      (P < 0.05). Similarly, concentrations of interleukin-1beta (2 d after mitogen)
      and interleukin-2 (1 d after mitogen) in media from postsupplementation PBMC were
      65 +/- 28% and 44 +/- 23%, respectively, of those for presupplementation PBMC (P
      < 0.01). Percentages of PBMC subsets were not affected by 14 d of biotin
      supplementation. Overall, this study provides evidence that administration of
      pharmacologic doses of biotin for 14 d decreases PBMC proliferation and synthesis
      of interleukin-1beta and interleukin-2.

PMID- 11340104
TI  - Beans, as a source of dietary fiber, increase cholecystokinin and apolipoprotein
      b48 response to test meals in men.
AB  - Dry beans lower plasma cholesterol, an effect that has been associated with both
      the fiber and the protein content of beans. The objective of this study was to
      determine the acute hormone and lipid responses to a test meal that contained dry
      beans as a source of dietary fiber. A crossover design was employed in which men
      consumed the test meal and a control meal in random order. Both meals contained
      egg, bread, jelly, orange juice, milk and margarine. The high fiber meal
      contained white beans, whereas the low fiber (control) meal contained rice and
      dry milk. The men maintained their normal dietary pattern and fasted overnight
      before the study days. After a fasting blood sample was drawn, the men consumed
      the test meal and blood samples were collected over the next 6 h. Blood samples
      were analyzed for cholecystokinin (CCK), insulin and glucose. Plasma was
      separated into lipoprotein fractions and the triglyceride, cholesterol,
      apolipoprotein (apo) B100 and B48 content of triglyceride-rich lipoproteins
      determined. Insulin and glucose responses did not differ significantly between
      test meals; however, the CCK response was twice as high after the bean-containing
      meal than after the low fiber meal (P = 0.03). The increase in apo B48
      concentration was significantly higher after the bean meal than after the low
      fiber meal (P < 0.05). Adding beans to a meal to increase fiber content prolongs
      the postprandial presence of intestinally derived lipoproteins and augments the
      CCK response to the meal.

PMID- 11340105
TI  - Oral exposure to butter, but not fat replacers elevates postprandial
      triacylglycerol concentration in humans.
AB  - Oral exposure to dietary fat augments the postprandial triacylglycerol (TAG)
      concentration. We investigated the TAG response after oral exposure to butter and
      selected fat replacers. At 2200 h, 17 healthy adults consumed 80 g of almonds and
      fasted until 0700 h. Safflower oil (50 g in 1-g capsules) was then consumed. Oral
      stimulation was provided periodically for 2 h as potatoes, potatoes containing
      butter or one of three fat replacers or no oral stimulation in random order at
      weekly intervals. Blood was collected at stipulated intervals for 8 h. Oral
      exposure to butter led to a significantly longer postprandial TAG elevation than
      the other treatments. The results could not be explained by differential stimulus
      ingestion, palatability or perceived fat content. There was no significant
      treatment effect on concentrations of serum oleic acid, apolipoprotein (apo)B-48
      or apoB-100, suggesting any oral exposure influence on release of dietary lipid
      stored in the lacteals or chylomicron and VLDL particle number contributed little
      to the postprandial TAG rise. In summary, oral exposure to butter elicited a
      greater postprandial TAG elevation than the tested fat replacers, possibly due to
      reduced TAG clearance.

PMID- 11340106
TI  - Supplementing lactating women with pureed papaya and grated carrots improved
      vitamin A status in a placebo-controlled trial.
AB  - Doubts have been raised about the effectiveness of carotene-containing foods in
      improving the vitamin A status of populations at risk. We investigated the effect
      of papaya and carrots on the vitamin A status of lactating women with 2- to 12-mo
      old infants in ZIMBABWE: The women were randomly assigned to three
      supplementation groups and a placebo group, and received 6 mg of beta-carotene
      capsules, 650 g pureed papaya, 100 g grated carrots or a placebo, daily for 60 d.
      All groups were given a meal containing 10 g of vegetable oil daily. Serum
      retinol, relative dose response, serum ferritin, hemoglobin and C-reactive
      protein were measured before and after the supplementation period. Mean serum
      retinol increased significantly after supplementation in the beta-carotene group
      (P < 0.001), the papaya group (P < 0.001) and the carrot group (P < 0.001), but
      not in the placebo group (P > 0.05). The relative dose response decreased
      significantly (P < 0.05) in the beta-carotene and papaya groups, but not in the
      carrot or placebo groups (P > 0.05). There was an increase in mean serum ferritin
      in all groups but the increase did not differ among groups. The hemoglobin
      increases in the beta-carotene and papaya groups were greater than that in the
      placebo group. We conclude that pureed papaya and grated carrots can improve the
      vitamin A and iron nutriture of lactating women. These findings reinforce the
      importance of plant food-based approaches in the control of vitamin A deficiency
      in low income countries.

PMID- 11340107
TI  - Nutritional and health consequences are associated with food insecurity among
      U.S. elderly persons.
AB  - The purpose of this study was to examine the consequences associated with food
      insecurity for the nutritional and health status of the elderly in the United
      STATES: The data analyzed were from the Third National Health and Nutrition
      Examination Survey (1988-1994) and the Nutrition Survey of the Elderly in New
      York State (1994). Multiple logistic and linear regression analyses were used to
      assess the extent to which food-insecure elderly were likely to have lower
      nutrient intake, skinfold thickness, self-reported health status and higher
      nutritional risk. Regardless of food insecurity status, older people consumed
      less than the recommended dietary allowance for eight nutrients. Food-insecure
      elderly persons had significantly lower intakes of energy, protein, carbohydrate,
      saturated fat, niacin, riboflavin, vitamins B-6 and B-12, magnesium, iron and
      zinc, as well as lower skinfold thickness. In addition, food-insecure elderly
      persons were 2.33 (95% confidence interval: 1.73-3.14) times more likely to
      report fair/poor health status and had higher nutritional risk. These results
      indicate that food-insecure elderly persons have poorer dietary intake,
      nutritional status and health status than do food-secure elderly persons. It is
      necessary to ensure the nutritional well-being of all elderly persons who are at
      nutritional and health risk, including those who are food insecure and have even
      poorer nutritional and health status than those who are food secure.

PMID- 11340108
TI  - Maternal night blindness increases risk of mortality in the first 6 months of
      life among infants in Nepal.
AB  - Night blindness occurs commonly among women during pregnancy in rural NEPAL: We
      examined the relationship between maternal night blindness and the risk of
      mortality occurring among infants in the first 6 mo of life. Stratified analysis
      by maternal night blindness status during pregnancy was done for 10,000 women
      participating in a randomized, placebo-controlled trial of vitamin A and beta
      carotene supplementation. Mortality of infants of non-night blind women in all
      three supplementation groups was similar, and when combined, was 63/1000 live
      births. Relative to this, mortality was higher by 63% [95% confidence interval
      (CI): 9-138%) and 50% (95% CI: -3 to 133%) among infants of night blind women
      receiving placebo and beta-carotene, respectively, but only by 14% (95% CI: -33
      to 93%) among those receiving vitamin A. Thus, 6-mo mortality was higher among
      infants of women who had night blindness during pregnancy. Maternal receipt of
      vitamin A reduced this risk.

PMID- 11340109
TI  - Diarrhea reduces the rates of cardiac protein synthesis in myofibrillar protein
      fractions in rats in vivo.
AB  - Although chronic diarrhea affects heart function and morphology, the pathogenic
      mechanisms are unknown. It was our hypothesis that diarrhea imposes metabolic
      stress to inhibit the synthesis of new contractile proteins. To test this
      hypothesis, we investigated the effects of lactose-induced diarrhea in rats. The
      groups were: 1) freely fed controls, 2) rats with lactose-induced diarrhea or 3)
      pair-fed rats. After 1 wk, hearts from the rats were subjected to subcellular
      fractionation techniques to isolate the major protein fractions, including
      myofibrillar proteins. The rates of protein synthesis were measured with
      concomitant assay of cardiac composition and plasma analytes. In comparison with
      the control group, diarrhea induced the following changes (P < 0.05): a decrease
      in heart weight, reduced RNA and mixed protein contents and a reduction in the
      fractional rate of mixed protein synthesis. There was a reduction in the content
      of all protein fractions. The fractional synthesis rate was reduced only for the
      myofibrillar fraction. Plasma insulin-like growth factor-I, but not
      corticosterone, was reduced. Plasma cholesterol and triglyceride concentrations
      were also reduced. In comparison with the pair-fed group, diarrhea induced the
      following changes (P < 0.05): a reduction in heart weight and fractional rate of
      mixed protein synthesis, reduced myofibrillar absolute synthesis rate and
      increased sarcoplasmic/myofibrillar fractional synthesis rate ratio. Plasma
      bicarbonate, triglyceride and urea concentrations were reduced, with an increase
      in albumin. Diarrhea impaired cardiac biochemistry, including a reduction in
      protein content and synthesis. A substantial proportion of these changes is due
      to anorexia, but the selective reduction in the synthesis of contractile proteins
      is a feature exclusive to the diarrhea group and may be due to reductions in
      plasma insulin-like growth factor-I.

PMID- 11340110
TI  - Small intestine epithelial barrier function is compromised in pigs with low feed
      intake at weaning.
AB  - Compromising alterations in gastrointestinal architecture are common during the
      weaning transition of pigs. The relation between villous atrophy and epithelial
      barrier function at weaning is not well understood. This study evaluated in vitro
      transepithelial transport by Ussing metabolic chambers, local alterations in T
      cell subsets and villous architecture at low energy intake level and their
      relation with lactose/protein ratios in the diet. Pigs (n = 66, 26 d old) were
      sampled either at weaning (d 0), d 1, 2 or 4 postweaning. Piglets received one of
      three diets at a low energy intake level, which differed in lactose and protein
      ratio as follows: low lactose/high protein (LL/HP), control (C), or high
      lactose/low protein (HL/LP). Mean digestible energy intake was 648 kJ/pig on d 1,
      1668 kJ/pig on d 2, 1995 kJ/pig on d 3 and 1990 kJ/pig on d 4 postweaning. The
      CD4(+)/CD8(+) T-lymphocytes ratio decreased after weaning (P < 0.05). Decreased
      paracellular transport (P < 0.01), greater villous height (P < 0.01), shallower
      crypts and lower villus/crypt ratios (P < 0.01) were observed on d 2 compared
      with d 0. Piglets consuming the HL/LP diet tended to have less paracellular
      transport (P < 0.10) and greater villous height (P < 0.10) compared with piglets
      fed the other diets. During the first 4 d postweaning, the effect of diet
      composition on mucosal integrity was not as important as the sequential effects
      of low energy intake at weaning. Stress and diminished enteral stimulation seem
      to compromise mucosal integrity as indicated by increased paracellular transport
      and altered T-cell subsets.

PMID- 11340111
TI  - Branched-chain amino acid aminotransferase activity decreases during development
      in skeletal muscles of sheep.
AB  - The catabolism of branched-chain amino acid (BCAA) differs between sheep and
      monogastric animals. The transamination of BCAA seems to be affected by
      development of the sheep. We studied the developmental changes in the activity
      and expression of the BCAA aminotransferase (BCAT) isoenzymes in skeletal muscle
      of sheep. Five muscles were taken from fetus, newborn, preruminant and ruminant
      lambs. BCAT specific activity and the contribution of each BCAT isoenzyme
      [mitochondrial and cytosolic (BCATm and BCATc, respectively)] were quantified
      using radioenzymatic and immunoprecipitation assays. BCATm and BCATc mRNAs were
      assessed by real-time reverse transcription-polymerase chain reaction. BCAT
      specific activities were 62% (diaphragma) to 83% (longissimus dorsi) lower in the
      ruminant lamb than in the fetal sheep. BCATm and BCATc were both expressed in
      sheep skeletal muscle at all developmental stages. BCATc was mainly responsible
      for the developmental decrease in BCAT specific activity. BCATc specific
      activities were 77% (diaphragma) to 92% (longissimus dorsi) lower in the ruminant
      lamb than in the fetal sheep, whereas BCATm specific activities were only 36%
      (semimembranosus) to 56% (longissimus dorsi) lower. BCATc and BCATm mRNAs in the
      longissimus dorsi were not affected by development of the sheep. The
      developmental decrease in BCATc activity, and to a lesser extent in BCATm
      activity, probably involves posttranscriptional mechanisms in sheep. The present
      results are consistent with lower in vivo metabolism of BCAA in ruminant than in
      the fetal sheep.

PMID- 11340112
TI  - Replacement of fish oil with rapeseed oil in diets of Atlantic salmon (Salmo
      salar) affects tissue lipid compositions and hepatocyte fatty acid metabolism.
AB  - Duplicate groups of Atlantic salmon post-smolts were fed five practical-type
      diets in which the added lipid was 100% fish oil [FO; 0% rapeseed oil (0% RO)],
      90% FO + 10% RO (10% RO), 75% FO + 25% RO (25% RO), 50% FO + 50% RO (50% RO) or
      100% RO, for a period of 17 wk. There were no effects of diet on growth rate or
      feed conversion nor were any histopathological lesions found in liver, heart,
      muscle or kidney. The greatest accumulation of muscle lipid was in fish fed 0%
      RO, which corresponded to significantly lower muscle protein in this group. The
      highest lipid levels in liver were found in fish fed 100% RO. Fatty acid
      compositions of muscle lipid correlated with RO inclusion in that the proportions
      of 18:1(n-9), 18:2(n-6) and 18:3(n-3) all increased with increasing dietary RO (r
      = 0.98-1.00, P < 0.013). The concentrations of eicosapentaenoic acid [20:5(n-3)]
      and docosahexaenoic acid [22:6(n-3)] in muscle lipid were significantly reduced
      (P < 0.05), along with total saturated fatty acids, with increasing dietary RO.
      Diet-induced changes in liver fatty acid compositions were broadly similar to
      those in muscle. Hepatic fatty acid desaturation and elongation activities,
      measured using [1-(14)C] 18:3(n-3), were increased with increasing dietary RO.
      Limited supplies of marine fish oils require that substitutes be found if growth
      in aquaculture is to be maintained such that fish health and product quality are
      not compromised. Thus, RO can be used successfully as a substitute for fish oil
      in the culture of Atlantic salmon in sea water although at levels of RO >50% of
      dietary lipid, substantial reductions occur in muscle 20:5(n-3), 22:6(n-3) and
      the (n-3)/(n-6) polyunsaturated fatty acid (PUFA) ratio, which will result in
      reduced availability of the (n-3) highly unsaturated fatty acids that are
      beneficial for human health.

PMID- 11340113
TI  - Increased rat mammary tissue vitamin A associated with increased vitamin A intake
      during lactation is maintained after lactation.
AB  - Although increases in dietary vitamin A increase milk vitamin A, little is known
      about effects of vitamin A intake on mammary tissue vitamin A levels during and
      after the reproductive cycle. First, we measured vitamin A concentrations in
      milk, mammary tissue and liver of lactating rats fed 0, 4, or 50 micromol of
      vitamin A/kg diet during pregnancy and through d 12 of lactation. Liver vitamin A
      concentration was significantly affected by diet in lactating females and pups 12
      d after parturition. Milk vitamin A concentrations were significantly higher (7.1
      +/- 2.2 micromol/L, n = 8) in dams fed 50 micromol/kg than in those fed 0 or 4
      micromol/kg (1.9 +/- 0.3, n = 5 and 2.9 +/- 0.7 micromol/L, n = 7; P < 0.001), as
      were mammary tissue vitamin A concentrations (5.1 +/- 1.1 versus 2.2 +/- 0.4 and
      2.4 +/- 0.6 nmol/g; P < 0.001). Next, we maintained female rats on 50 or 10
      micromol vitamin A/kg diet during pregnancy and lactation and then on 4
      micromol/kg diet after pups were weaned on d 21. On d 21, mammary tissue vitamin
      A concentrations were 3.14 +/- 0.75 versus 1.52 +/- 0.21 nmol/g in dams fed 50
      versus 10 micromol/kg (n = 4/group; P < 0.001). Mammary tissue vitamin A
      concentrations were not significantly affected by time from 7 to 49 d after
      lactation and averaged 8.5 +/- 0.4 and 4.9 +/- 0.8 nmol/g on d 49 in dams fed 50
      versus 10 micromol/kg (n = 4; P < 0.001). We conclude that diet-induced
      differences in rat mammary tissue vitamin A developed during pregnancy and
      lactation are maintained for > or =7 wk after lactation.

PMID- 11340114
TI  - Estimation of conjugated linoleic acid intake by written dietary assessment
      methodologies underestimates actual intake evaluated by food duplicate
      methodology.
AB  - Conjugated linoleic acids (CLA) are conjugated isomers of linoleic acid, which
      may promote health with regard to cancer, heart disease, diabetes, bone
      formation, growth modulation and immunity. The c9,t11 isomer of CLA, rumenic acid
      (RA), is the major isomer present in the diet. However, dietary intakes of CLA
      and RA by humans have not been examined rigorously, nor has the relationship
      between dietary CLA or RA and health (e.g., body composition). Three-day dietary
      records (DR) were collected from adult men (n = 46) and women (n = 47) and
      analyzed using a nutrient database modified to contain total CLA and RA.
      Simultaneously, 3-d food duplicates (FD) were collected to determine analytically
      individual fatty acid intakes, including those of total CLA and RA. Chronic total
      CLA and RA intakes were estimated using a semiquantitative food-frequency
      questionnaire (FFQ). Body composition was estimated using body mass index and
      percentage of body fat. Total CLA intake was estimated from FD to be 212 +/- 14
      and 151 +/- 14 mg/d (mean +/- SEM) for men and women, respectively; RA intake was
      estimated to be 193 +/- 13 and 140 +/- 14 mg/d for men and women, respectively.
      In general, CLA and RA intakes estimated by DR and FFQ were significantly lower
      than those estimated by FD. Body composition was not significantly related to
      dietary total CLA or RA intake. In conclusion, results suggest that DR and FFQ
      methodologies are not reliable estimators of individual total CLA and RA intakes
      and may underestimate total CLA and RA intakes of groups. Intake of total CLA and
      RA was found to be significantly lower than that suggested previously by others.

PMID- 11340115
TI  - A protein-restricted diet during pregnancy alters in vitro insulin secretion from
      islets of fetal Wistar rats.
AB  - Previous studies indicate that insulin secretion from the fetuses of dams fed a
      low protein (LP) diet is reduced in response to leucine or arginine. The aim of
      this study was to locate the defect in the insulin secretion pathway induced by a
      LP diet during gestation. The effects of various secretagogues acting at
      different levels of the insulin secretion cascade were investigated in vitro in
      fetal islets from dams fed either a normal or a LP diet during pregnancy. Insulin
      content, insulin secretion and the cAMP content were then measured. Although
      insulin content of LP islets did not differ from that of control islets, insulin
      secretion from LP fetal islets was reduced when challenged by amino acids or cAMP
      enhancers. This reduction did not appear to be related solely to an altered islet
      cAMP content. An impairment of insulin secretion remained after stimulation of
      fetal LP islets with either metabolic or nonmetabolic secretagogues. The insulin
      secretion by LP islets was restored to normal, however, with barium or
      cytochalasin-B. These findings demonstrate that an in utero isocaloric LP diet
      impairs insulin secretion of the fetus. This alteration is located at the
      exocytosis step in the insulin secretion cascade and not in the insulin pool of
      the beta cell.

PMID- 11340116
TI  - Green tea suppresses lipopolysaccharide-induced liver injury in d-galactosamine
      sensitized rats.
AB  - We conducted a series of in vivo experiments to clarify the hepatoprotective
      activity of green tea against lipopolysaccharide (LPS) + D-galactosamine (GalN)
      induced liver injury and to elucidate the mechanism by which green tea exerts its
      effect in 7-wk-old male Wistar rats. Liver injury was assessed by plasma alanine
      aminotransferase and aspartate aminotransferase activities. Green tea extract
      significantly suppressed LPS + GalN-induced liver injury when added to the diet
      (30 or 35 g/kg) and fed to rats for 14 d or when force-fed alone (0.4-1.2 g/kg
      body) 1.5 h before the injection of drugs. Although all five of the fractions
      extracted from green tea extract with different organic solvents had significant
      suppressive effects, the caffeine-containing fraction exhibited the strongest
      effect, suggesting that the protective effect of green tea against LPS + GalN
      induced liver injury is attributable mainly to caffeine. Authentic caffeine also
      significantly suppressed LPS + GalN-induced liver injury when added to the diet
      (2 g/kg) and fed to rats for 14 d. Dietary green tea suppressed LPS + GalN
      induced apoptosis of liver cells, as assessed by DNA fragmentation. However,
      dietary green tea did not suppress LPS-induced enhancement of plasma
      concentration of tumor necrosis factor (TNF)-alpha, the cytokine that is thought
      to play a pivotal role in the pathogenesis of LPS-induced liver injury, although
      it significantly suppressed plasma concentrations of interleukin (IL)-1beta, IL
      2, IL-4, IL-6, IL-10 and interferon (IFN)-gamma. TNF-alpha + GalN-induced liver
      injury and apoptosis were also suppressed by dietary green tea. In contrast,
      dietary caffeine significantly suppressed LPS-induced enhancement not only of
      plasma IL-1beta, IL-6, IL-10 and IFN-gamma concentrations, but also of TNF-alpha
      concentration. The results suggest that green tea might suppress LPS + GalN
      induced liver injury mainly through the inhibition of TNF-alpha-induced apoptosis
      of hepatocytes, rather than through the suppression of TNF-alpha production,
      although the suppressed production of TNF-alpha may be associated with the
      hepatoprotective effect of caffeine.

PMID- 11340117
TI  - Dietary trans fatty acids combined with a marginal essential fatty acid status
      during the pre- and postnatal periods do not affect growth or brain fatty acids
      but may alter behavioral development in B6D2F(2) mice.
AB  - The objective of this study was to investigate whether dietary trans fatty acids
      (TFA) during the pre- and postnatal periods would exacerbate the effects of
      marginal essential fatty acid (EFA) status on growth, brain long-chain
      polyunsaturated fatty acids (LC-PUFA) and behavioral development in B6D2F(2)
      mice. Pregnant B6D2F(1) females were randomly assigned to one of the following
      three diets: marginal EFA plus 22% trans 18:1 (mEFA + TFA); marginal EFA (mEFA);
      and control (CON). The total 18:1 content in all diets was similar. The offspring
      were weaned and maintained on the same diets. Both the mEFA and mEFA + TFA groups
      had reduced growth and brain weight compared with CON, but did not differ from
      one another. As expected, the mEFA and mEFA + TFA groups had reduced
      docosahexaenoic acid [DHA; 22:6(n-3)]) and increased 22:5(n-6) concentrations in
      brain phosphatidylcholine (PC) and phosphatidylethanolamine (PE) compared with
      the CON group, but again did not differ from one another. Reversal learning in
      the T-water maze was significantly slower in the mEFA + TFA groups compared with
      the mEFA group and both were slower than the CON group. These findings illustrate
      that TFA combined with a marginal EFA status do not exacerbate the effects of
      marginal EFA status on growth or brain LC-PUFA. However, long-term effects of
      dietary TFA during the pre- and postnatal period on behavioral development and
      neural function should be investigated in future studies.

PMID- 11340118
TI  - In vitro inhibition of proliferation of estrogen-dependent and estrogen
      independent human breast cancer cells treated with carotenoids or retinoids.
AB  - Both estrogen-receptor (ER) positive MCF-7 and ER-negative Hs578T and MDA-MB-231
      human breast cancer cells were treated with carotenoids (beta-carotene,
      canthaxanthin and lycopene) and retinoids (all-trans-, 9-cis- and 13-cis-retinoic
      acid and all-trans-retinol). Among carotenoids, beta-carotene significantly
      reduced the growth of MCF-7 and Hs578T cells, and lycopene inhibited the growth
      of MCF-7 and MDA-MB-231 cells. Canthaxanthin did not affect the proliferation of
      any of the three cell lines. All-trans- and 9-cis-retinoic acid significantly
      reduced the growth of both MCF-7 and Hs578T cells, whereas 13-cis-retinoic acid
      and all-trans-retinol had a significant effect only on MCF-7 cells. MCF-7 and
      Hs578T cells treated with all-trans-retinoic acid (all-t-RA) were further studied
      for the mechanism behind growth inhibition. Retinoic acid receptors alpha and
      gamma (RARalpha, gamma) in MCF-7 cells and RARalpha, beta and gamma in Hs578T
      cells were not induced by all-t-RA treatment at either the protein or mRNA level.
      Hs578T cells treated with all-t-RA had significantly more cells in the G0/G1
      stage of the cell cycle, but the same was not observed for MCF-7 cells. All-t-RA
      induced a dose-dependent cell death in MCF-7 cells, which may be a necrotic
      phenomenon. These results demonstrate that ER status is an important, although
      not essential factor for breast cancer cell response to carotenoid and retinoid
      treatments, and the mode of action of all-t-RA in MCF-7 and Hs578T cells is not
      through the induction of RAR. Other mechanistic pathways that are either followed
      by or concomitant with growth inhibition are possible.

PMID- 11340119
TI  - Stability of vitamin B-6-dependent aminotransferase activity in frozen packed
      erythrocytes is dependent on storage temperature.
AB  - Pyridoxal 5'-phosphate (PLP) stimulation of erythrocyte alanine and aspartate
      aminotransferase (EALT, EAST) activities is a frequently used functional measure
      of vitamin B-6 status. Stability of enzyme activities and activity coefficients
      (AC, stimulated / unstimulated) was assessed in packed erythrocytes frozen at 
      20, -80 degrees C and under liquid nitrogen (-196 degrees C). Activities of EALT
      and EAST, with and without added PLP, were determined in fresh erythrocytes (d 0)
      and frozen samples on d 1, 7, 14, 28, 58 and 84. In -20 degrees C samples, EALT
      basal activity decreased 17 and 22% (P < or = 0.05 for both) by d 58 and 84,
      respectively, and EAST basal activity decreased 40% (P < or = 0.05) by d 58. In 
      80 and -196 degrees C samples, EALT and EAST basal activities did not change
      significantly. Activity coefficients did not differ significantly from d 0 at any
      storage temperature, but EAST-AC increased 9-19% (nonsignificant) in samples
      stored at -20 and -80 degrees C for 7 to 84 d. Additionally, EAST-AC was
      significantly higher in -20 than -80 and -196 degrees C samples on d 1 and 58,
      respectively. Erythrocytes may be frozen for 28 d at -20 degrees C and 84 d at 
      80 degrees C before analysis for EALT; for EAST, activity should be measured on
      fresh erythrocytes.

PMID- 11340120
TI  - Limited role of transferrin in manganese transport to the brain.

PMID- 11340123
TI  - Selected body composition methods can be used in field studies.
AB  - This article provides an overview of the present status of in vivo body
      composition methodologies that have potential for use in field studies. The
      methods are divided into four general categories: anthropometric indices and
      skinfold, body volume measurements, body water measurements including
      bioelectrical methods, and imaging techniques. Among the newest technologies are
      air-displacement plethysmography, three-dimensional photonic scanning,
      multifrequency bioelectrical impedance spectroscopy and whole-body tomography
      using electrical impedance and magnetic induction. These newer approaches are
      compared with the established reference methods. The advantages and limitations
      of each technique as a field method are presented relative to the corresponding
      concepts of an ideal method.

PMID- 11340124
TI  - Noninvasive and minimally-invasive optical monitoring technologies.
AB  - With recent advancements in micro-fabrication and nano-fabrication techniques as
      well as advancements in the photonics industry, there is now the potential to
      develop less invasive portable sensors for monitoring micronutrients and other
      substances used to assess overall health. There have been many technology
      innovations in the central laboratory for these substances for overall health
      status but the primary motivation for the research and development of a portable
      field instrument has come from a diabetic patient and market-driven desire to
      minimally invasively or noninvasively monitor glucose concentrations in vivo.
      Such a sensor system has the potential to significantly improve the quality of
      life for the estimated 16 million diabetics in this country by making routine
      glucose measurements less painful and more convenient. In addition, there is a
      critical need for the development of less invasive portable technologies to
      assess micronutrient status (iron, vitamin A, iodine and folate), environmental
      hazards (lead) and for other disease-related substances, such as billirubin for
      infant jaundice. Currently, over 100 small companies and universities are working
      to develop improved monitoring devices, primarily for glucose, and optical
      methods are a big part of these efforts. In this article many of these
      potentially less invasive and portable optical sensing technologies, which are
      currently under investigation, will be reviewed including optical absorption
      spectroscopy, polarimetry, Raman spectroscopy and fluorescence.

PMID- 11340126
TI  - The role of a new noninvasive imaging technology in the diagnosis of anemia.
AB  - Traditionally, numerical data regarding the status of a patient are a combination
      of measurements made at the point of care (POC) and those made in the laboratory
      on specimens withdrawn from the patient. We report here on our experiences with a
      new method for a noninvasive determination of anemia, as defined by blood
      hemoglobin (Hb) concentration. This method is based on a novel technology,
      orthogonal polarization spectral imaging, which provides high quality digitized
      images of the microcirculation using reflected light. Measurements of Hb, based
      on the analysis of these images at the POC, were found to compare favorably with
      results obtained with traditional laboratory methods. Additional advantages of
      these new POC technologies are that they will make possible completely new
      measurements that may have no direct analog with existing methods. For example,
      orthogonal polarization spectral imaging can give feedback regarding
      microvascular density, which also may be reduced in anemic subjects. This
      information may give earlier and different insights regarding the patient status
      in nutritional deficiency anemia than an Hb concentration only. However,
      additional research will be required to confirm the accuracy and utility of this
      measurement, especially in adult and pediatric populations, where anemia is more
      commonly encountered. The ultimate success of POC testing will require
      collaboration between the attending health care professional, the laboratory and
      institutional management to rapidly assimilate improved methodologies and new
      information to provide benefits to the patient.

PMID- 11340125
TI  - Molecular approaches to studying nutrient metabolism and function: an array of
      possibilities.
AB  - Genomics promises to revolutionize the study of nutrient function and
      requirements and, thereby, solidify the connection of this field to basic
      sciences, such as molecular genetics. In this short review, we address the
      general concepts and techniques used in high throughput measurements of gene
      expression. We also speculate on how these technologies can be used to further
      our understanding of basic metabolism and nutrient regulation of gene expression
      in developmental and pathological conditions.

PMID- 11340127
TI  - Mass spectrometry methods for metabolic and health assessment.
AB  - Beginning in the mid 1960s, mass spectrometry was introduced in a few academic
      laboratories for the analysis of organic acids by gas chromatography-mass
      spectrometry. Since then, multiple-stage mass spectrometers have become available
      and many new applications have been developed. Major advantages of these new
      techniques include their ability to rapidly determine many different compounds in
      complex biological matrices with high sensitivity and in sample volumes of
      usually < 100 microL. A high sample throughput is further realized because
      extensive sample preparations are often not necessary. However, because the
      technical know-how is not yet widely available and significant experience is
      required for correct interpretation of results, these methods are being
      implemented slowly in routine clinical laboratories as opposed to research
      laboratories. Several of these new applications are considered with regard to
      clinical medicine.

PMID- 11340128
TI  - Human saliva as a diagnostic specimen.
AB  - Human saliva can be easily obtained by noninvasive techniques and contains many
      analytes of interest for screening, diagnosis and monitoring. These include
      steroid and other nonpeptide hormones, therapeutic drugs, drugs of abuse and
      antibodies. Numerous studies in the past 40 y have shown correlations between
      serum and saliva levels. Both diurnal and monthly profiles of hormone levels
      parallel traditional serum patterns. Multiple specimens for steroid hormone
      analysis can be easily collected by the patient, at home, to monitor fertility
      cycles, menopausal fluctuations, stress and other diurnal variations. Drug doses
      can be monitored without inconvenient and costly visits to blood-drawing
      facilities. Antibody levels can be determined to screen for infectious diseases.
      Saliva can be collected directly by spitting into a tube or with one of several
      devices, each of which has its own special advantages and disadvantages. Salivary
      levels of steroid hormones and other analytes that are protein bound in serum
      reflect the unbound and active concentration of the hormone. Saliva can be used
      as a diagnostic specimen not only to obtain information more inexpensively and
      efficiently than serum, but also to provide information not readily available
      from serum testing.

PMID- 11340129
TI  - Innovative approaches to vitamin A assessment.
AB  - The health and sight of millions of children are compromised each year as a
      consequence of vitamin A (VA) deficiency. Serum retinol is the most commonly used
      indicator of VA status. Unfortunately, its use is impractical for national
      surveys because it involves collection of venous blood, centrifugation and frozen
      storage before analysis. To make VA assessment more practical, we have developed
      approaches incorporating dried blood spots (DBS) or portable instrumentation. DBS
      have been used as a sample matrix to screen neonates for many biochemical
      compounds. Until recently, it was not thought that VA was stable in DBS. However,
      we demonstrated that the measure of DBS retinol correlates well with serum
      retinol in both healthy adults (r(2) = 0.88-0.90) and compromised populations
      (r(2) = 0.73-0.84). Compared with serum retinol, the sensitivity and specificity
      of detecting VA deficiency by DBS retinol range from 73 to 93% and from 90 to
      100%, respectively. Although few data are available, retinol binding protein
      (RBP) can also be measured in DBS. RBP has been used as a surrogate marker for
      serum retinol. Correlations coefficients (r(2)) between serum RBP and serum
      retinol range from 0.4 to 0.8. In addition, work has been done to develop
      portable instrumentation to measure VA status in the field. A fluorometer has
      been optimized for VA fluorescence and is linear into the deficient range for the
      direct fluorimetric measurement of serum holo-RBP. Progress is being made to use
      the instrument to directly measure holo-RBP in a drop of whole blood.

PMID- 11340130
TI  - Use of filter paper for the collection and analysis of human whole blood
      specimens.
AB  - The Centers for Disease Control and Prevention and its partners have been
      operating the Newborn Screening Quality Assurance Program for >20 y. The program
      helps participating laboratories to evaluate and improve the quality of their
      newborn-screening testing efforts by providing quality control dried blood spot
      materials and proficiency-testing materials for the external evaluation of
      screening programs. The Newborn Screening Quality Assurance Program provides an
      independent evaluation of filter papers approved by the Food and Drug
      Administration for the collection of blood for clinical tests. These activities
      have created a mechanism for the validation of the filter paper blood collection
      device and the standardization of materials and methods for the analysis of dried
      blood spots.

PMID- 11340131
TI  - 13C breath tests: visions and realities.
AB  - Breath tests have been used in research laboratories for over 25 y. Originally,
      the tests were based on the use of (14)C, rather than on the nonradioactive
      isotope, (13)C. When (13)C became widely available at a reasonable cost, research
      groups in the United States and Europe developed methodologies to measure (13)C
      abundance in samples of CO(2). The tests used a variety of substrates and
      measured pancreatic function, fat absorption, bacterial overgrowth and P(450)
      mixed-function oxidase. Thus far, the only test to be approved by the Food and
      Drug Administration is the (13)C-urea breath test. This manuscript describes the
      process by which approval is gained, and indicates the steps necessary for other
      tests to receive Food and Drug Administration approval.

PMID- 11340132
TI  - Synthesis of a symposium: innovative non- or minimally-invasive technologies for
      monitoring health and nutritional status in mothers and young children.

PMID- 11340133
TI  - SCVIR reporting standards for the treatment of acute limb ischemia with use of
      transluminal removal of arterial thrombus.

PMID- 11340134
TI  - Uterine artery embolization for leiomyomata: resource use and cost estimation.
AB  - PURPOSE: The objective of this study is to provide an assessment of the facility
      cost associated with uterine artery embolization (UAE) for leiomyomata and to
      provide a basis for the estimation of cost so as to compare UAE with surgical
      approaches. MATERIALS AND METHODS: Information was gathered from the
      clinical/accounting system for 23 patients who had UAE performed at a single
      institution. Cost-to-charge ratios and microcosting were employed to derive cost
      estimates. A detailed meta-analysis was also performed on the resource use
      parameters reported in the literature. RESULTS: Facility costs range from 2,058
      dollars to 4,951 dollars and the mean total cost is 3,080 dollars. The radiology
      procedure and observation stay are the largest contributors to facility cost. The
      average length of stay is 21.5 hours with a range from 8 hours to 48 hours. The
      estimates from this analysis provide a good approximation of facility cost; there
      are no significant differences in resource use between this study and the meta
      analysis. CONCLUSIONS: The facility cost of UAE (3,080 dollars) compares
      favorably with hysterectomy, the cost of which ranges from 3,100 dollars to 4,900
      dollars depending on the type of procedure performed. This cost information can
      be used to analyze the cost effectiveness of UAE compared to alternate therapies.

PMID- 11340135
TI  - Elective endovascular treatment of descending thoracic aortic aneurysms and
      chronic dissections with stent-grafts.
AB  - PURPOSE: To report our experience of endovascular stent-graft placement in
      patients with descending thoracic aortic dissections and aneurysms and to
      evaluate the feasibility, safety, and clinical outcomes of the treatment.
      MATERIALS AND METHODS: Stent-grafts were placed in the descending thoracic aortas
      of 23 patients with saccular aneurysms (n = 11) and Stanford type B chronic
      aortic dissections of the descending thoracic and abdominal aorta (n = 12). All
      stent-grafts were individually constructed of self-expandable stainless steel
      stents covered with polytetrafluoroethylene. Vascular access was achieved through
      the femoral artery in all patients. Clinical status of each patient was monitored
      and postoperative CT was performed within 1 month of the procedure and at 3-12
      month intervals after the procedures. RESULTS: Successful exclusion of the
      primary entry tears of dissections and the inlets of saccular aneurysms was
      achieved in all but two patients with aortic dissection. The overall technical
      success rate was 91.3% (dissection: 10 of 12 = 83%; aneurysm: 11 of 11 = 100%).
      All patients in whom technical success was achieved showed complete thrombosis
      and significant decrease in diameter of the thoracic false lumen (preoperative:
      5.3 cm +/- 0.9; postoperative: 4.3 cm +/- 0.9; P = .004) or aneurysm sac
      (preoperative: 5.3 cm +/- 1.7; postoperative: 2.8 cm +/- 2.5; P = .001). In
      addition, five patients demonstrated complete resolution of the dissected
      thoracic false lumen (n = 2) and aneurysm sac (n = 3). However, in all patients
      with aortic dissection, the abdominal aorta was not significantly changed in size
      (P = .302) and shape and their false lumen flows remained persistent. Immediate
      postoperative complications were detected in 12 patients (52%); 10 had fever,
      leukocytosis, and elevation of C-reactive protein, another had wound infection,
      and another had transient abdominal pain. Three patients died 2, 3, and 12 months
      after the procedure: one from septic shock, another from underlying
      mediastinitis, and the other from an unexplained cause. The remaining 20 patients
      were well after the procedure (1-9 days; mean, 3 days), without any stent-graft
      related complications or discomfort (follow up period: 10-65 mo; mean: 25.1 mo +/
      15.6). The cumulative survival rate after the stent graft was 100% at 30 days
      and 91% at 12 months. CONCLUSIONS: For treatment of aortic dissection and
      saccular aneurysm of the descending thoracic aorta, endovascular stent-graft
      repair may be a technically feasible and effective treatment modality.

PMID- 11340136
TI  - Randomized controlled trial of aspiration needle versus automated biopsy device
      for transjugular liver biopsy.
AB  - PURPOSE: The efficacy and safety of transjugular liver biopsy used to obtain
      liver specimens in patients with coagulation disorders have been widely proven.
      However, histopathologic examination is not always possible because of fragmented
      samples provided by the aspiration technique. Recently, an automated device with
      a Tru-Cut-type needle was designed. In this randomized controlled trial, the use
      of this new device is compared with the traditional method in terms of efficacy
      and safety. METHOD: Fifty-six patients were included in the study; 28 were
      randomized to undergo the aspiration technique and 28 were randomized to undergo
      the automated biopsy technique. RESULTS: Correct positioning of the device was
      achieved in 93% of patients undergoing the aspiration technique and 96% of
      patients undergoing the automated biopsy technique (P = NS). Mean duration of the
      procedure and total number of passes were significantly higher in the aspiration
      needle group than in the automated device group (22.6 min +/- 12.6 vs 15.5 min +/
      9.4; P = .03, and 3.3 min +/- 1.9 vs 1.5 min +/- 0.63; P < .001, respectively).
      The number of portal tracts was significantly higher in the automated device
      group (4.7 +/- 2.5 vs. 2.7 +/- 3.4; P < .05). Adequate specimens for
      histopathologic evaluation were obtained in 26 patients in the automated device
      group and 24 patients in the aspiration needle group (92.8% vs 85.7%; P = NS),
      but a definite histopathologic diagnosis was more frequently obtained with the
      automated biopsy device (68% vs 43%; P = .05). No significant differences were
      observed in complication rates (7.14% vs. 10.7%; P = NS). CONCLUSION: The
      automated biopsy device for transjugular liver biopsy is more effective than an
      aspiration needle in obtaining good samples for a definite histologic diagnosis.

PMID- 11340137
TI  - US-guided needle aspiration and catheter drainage as an alternative to open
      surgical drainage for uniloculated neck abscesses.
AB  - PURPOSE: To prospectively evaluate the effectiveness of ultrasound (US)-guided
      needle aspiration and catheter drainage as an alternative to open surgical
      drainage of uniloculated neck abscesses. MATERIALS AND METHODS: Fifteen
      consecutive patients (11 female, four male; age range from 18 days to 78 years,
      mean 42.5 y +/- 22.4) diagnosed with deep neck infections associated with
      uniloculated neck abscesses were treated. The patients were originally scheduled
      for surgical incision and drainage after a period of unsuccessful treatment with
      antibiotics. US-guided needle aspiration (in 10 patients) and US-guided catheter
      drainage (in five patients) were performed under local anesthesia. Open surgical
      drainage was performed when US-guided drainage procedures failed. RESULTS:
      Surgical open drainage was avoided in 13 of the 15 patients (87%). An average of
      6 mL of pus was obtained in patients in the needle aspiration group and 140 mL of
      pus was drained by catheter. One patient had a recurrent pyogenic lymphadenitis
      at the same location and was treated successfully by repeated needle aspiration.
      No complications occurred in this study. CONCLUSION: In a selected group of
      patients without imminent airway obstruction, most uniloculated neck abscesses
      may be managed initially by US-guided needle aspiration and catheter drainage
      before resorting to open surgical drainage.

PMID- 11340138
TI  - Ethanol sclerotherapy of venous malformations: evaluation of systemic ethanol
      contamination.
AB  - PURPOSE: To evaluate blood ethanol concentrations immediately after percutaneous
      ethanol sclerotherapy of venous malformations (VMs). MATERIALS AND METHODS:
      Thirty consecutive sclerotherapy procedures were performed for VMs in various
      anatomic sites. In a prospective study, the blood parameters monitored were
      ethanol plasma level (immediately after the procedure), plasma haptoglobin (Hp;
      before and after the procedure), and standard blood analysis including urea,
      creatinine, bilirubin, and lactic dehydrogenase (LDH) levels during the hospital
      stay. RESULTS: The mean amount of 94% ethanol injected was 19.7 mL (0.03-0.78
      g/kg of body weight). The observed systemic ethanol levels ranged from 0 to 1.16
      g/L (mean, 0.33 g/L, SD = 0.33). The relationship between the observed plasmatic
      ethanol level (ETOH plasma) measured immediately after the procedure and the
      maximum expected plasmatic ethanol amount (ETOH max) was linear and significant
      (correlation coefficient r = 0.91 for all lesions, r = 0.96 for lesions without
      visible venous drainage, r = 0.86 for lesions with visible draining veins, and r
      = 0.93 for lobulated VMs). Minimal changes were observed for indicators of
      hemolysis: macroscopic hemoglobinuria in five of 30, abnormal Hp level in seven
      of 30, and increase in LDH and increase in bilirubinemia in one case each.
      CONCLUSIONS: Systemic ethanol contamination during sclerotherapy of VMs could be
      detected in 25 of 30 cases (83.3%). The plasmatic ethanol level was directly
      proportional to the amount of ethanol injected and not dependent on the VM
      morphology, venous drainage, or injection technique. Clinicians and
      interventional radiologists must be aware of this massive ethanol outflow during
      percutaneous sclerotherapy of VMs and its potentially serious systemic
      complications.

PMID- 11340139
TI  - Delivery of endothelial cells to balloon-dilated rabbit arteries with use of a
      local delivery catheter.
AB  - PURPOSE: Experiments were performed to determine if a local delivery catheter
      could deliver endothelial cells that would be retained on the luminal surface of
      balloon-dilated arteries. MATERIALS AND METHODS: Six New Zealand White rabbits
      underwent carotid catheterization, arteriography, and balloon angioplasty of an
      external iliac artery. A local delivery catheter (Dispatch) was then positioned
      at the site of angioplasty and the 3-mm balloon was inflated. Cultured rabbit
      endothelial cells (1.26 +/- 0.3 x 10(6) ), previously stained with fluorescent
      dye PKH26, were delivered to the artery in three infusions separated by 10
      minutes. The delivery balloon was deflated and removed 25 minutes after the last
      delivery. The arteries were then perfusion-fixed in situ at physiologic pressure,
      removed, and divided into four segments, and the segments were rapidly frozen and
      cryosectioned. Eight sections from each arterial segment were examined by means
      of epifluorescence microscopy. The luminal surface of each artery was visually
      divided into eight sectors of equal length and each sector was assigned a score
      based on the degree of endothelial coverage (0 = no coverage, 1 = <50% coverage,
      2 = >50% coverage). RESULTS: The endothelial coverage score for the six arteries
      averaged 0.40 +/- 0.46 (SD; range, 0.04-1.24). Areas of each artery receiving
      scores of 0, 1, and 2 averaged 68%, 25%, and 7%, respectively. Average coverage
      scores were 0.42, 0.38, 0.51, and 0.28 for individual segments along the length
      of the artery. CONCLUSIONS: The Dispatch local delivery catheter is able to
      deliver endothelial cells that adhere to balloon-dilated arteries. Although the
      magnitude of cellular retention was modest and varied among arteries, the
      retention along the length of each artery was constant.

PMID- 11340140
TI  - Influence of stent edge angle on endothelialization in an in vitro model.
AB  - PURPOSE: To investigate the influence of topographic features in the path of
      migrating endothelial cells, specifically the effect of edge angle of
      intravascular metallic material on endothelialization. MATERIALS AND METHODS:
      Flat 1-cm x 1-cm 316-L pieces of stainless steel were placed on confluent
      monolayers of human aortic endothelial cells. The thickness of each metal piece
      was ground to achieve an edge angle of 35 degrees, 70 degrees, 90 degrees, or 140
      degrees (n = 6 each) in relation to the endothelial surface. Migration distance
      and density of endothelial cell coverage on the metal pieces were measured in
      groups of six each under static conditions at 4, 7, and 11 days and flow
      conditions (16 dynes/cm(2)) at 4 days. RESULTS: Endothelial cell migration
      distance along the surface of the pieces with edge angles of 35 degrees was
      significantly greater than that with those with larger angles (P < .05) under
      static and flow conditions. The migration distances on the 35 degrees piece were
      87.5%, 47.3%, 57.1%, and 66.1% greater than those on the 90 degrees piece at the
      upstream, downstream, right, and left edges, respectively. There were no
      significant differences in cell density among different angle groups under flow
      or static conditions. CONCLUSION: The edge angle of intravascular metallic
      material has an influence on the rate of endothelialization. A smaller edge angle
      facilitates endothelialization over metallic material when compared to a larger
      angle. These results demonstrate the importance of metallic stent profile on
      endothelialization rate.

PMID- 11340141
TI  - In vitro hemodynamic evaluation of a Simon nitinol vena cava filter: possible
      explanation of IVC occlusion.
AB  - PURPOSE: To evaluate the local hemodynamics in the region of the Simon nitinol
      filter (SNF), used to prevent pulmonary emboli by capturing clot and promoting
      lysis. MATERIALS AND METHODS: The hemodynamics of the Simon nitinol inferior vena
      cava (IVC) filter were evaluated under steady flow (Re = 600) in a 20-mm-diameter
      IVC model. The photochromic dye tracer technique was used to estimate the
      velocity and wall shear stress. These flow features were determined for the
      unoccluded and partially occluded (clot volume = 1,500 mm(3)) states of the SNF
      along its center plane. RESULTS: A region of low velocities developed around the
      central axis of the filter extending from the leading edge of the central strut
      to the filter tip. This phenomenon was created by the strong redirection of flow
      toward the periphery of the filter. With the presence of the clot, these effects
      were enhanced, causing flow separation and recirculation. In addition, the shear
      stress on the hip of the clot was about 30 times that of the upstream value, and
      turbulence developed in the near-downstream region. CONCLUSIONS: The extended
      region of almost-stagnant flow near the midsection of the umbrella region could
      lead to organization of thrombus and fibrin mesh network development. The
      presence of a simulated clot led to a significant increase in the size of the
      stagnant, thrombus-prone region as well as turbulence, which, overall, may
      contribute to caval occlusion.

PMID- 11340142
TI  - Microwave coagulation therapy with interruption of hepatic blood in- or outflow:
      an experimental study.
AB  - PURPOSE: To determine how interruption of hepatic blood in- or outflow affects
      the coagulation diameter of microwave coagulation therapy (MCT) in the liver.
      MATERIALS AND METHODS: Laparotomic MCT at 60 W for 1 minute was performed in 11
      Landrace pigs. MCT was performed under six different conditions: without
      occlusion (Group N; in seven lobes of seven pigs); with occlusion of the hepatic
      artery (Group A; in five lobes of five pigs); with occlusion of the portal vein
      (Group P; in five lobes of five pigs); with occlusion of the hepatic artery and
      portal vein (Group AP; in six lobes of six pigs); with occlusion of the hepatic
      vein (Group V; in five lobes of four pigs); and with occlusion of the hepatic
      artery and vein (Group AV; in seven lobes of seven pigs). The maximum diameters
      for each group were compared. RESULTS: The coagulation diameters (mean +/- SD)
      were 8.5 mm +/- 2.0, 10.0 mm +/- 1.6, 14.3 mm +/- 2.5, 14.4 mm +/- 2.4, 13.0 mm
      +/- 0.8, and 14.4 mm +/- 1.5 for Groups N, A, P, AP, V, and AV, respectively. The
      coagulation diameters for groups P, AP, V, and AV were statistically larger than
      those for groups N and A (P < .05). There was no significant difference between
      the coagulation diameters of Groups P, AP, V, and AV. CONCLUSION: The coagulation
      diameter depends mainly on the portal venous flow. In addition of direct
      interruption of the portal vein, interruption of the hepatic vein can also result
      in a substantial increase in the coagulation diameter.

PMID- 11340143
TI  - US-guided nephrostomy with the aid of a magnetic field-based navigation device in
      the porcine pelvicaliceal system.
AB  - PURPOSE: To assess the technique and feasibility of ultrasound (US)-guided
      nephrostomy performed with the aid of a magnetic field-based navigation device.
      MATERIALS AND METHODS: Twelve percutaneous nephrostomy procedures were performed
      in seven domestic pigs under real-time US guidance employing a navigation system.
      Two magnetic field sensors registered the actual position of the puncture needle
      and the US transducer. The actual needle position and the aimed puncture tract
      were graphically projected into the real-time US images, allowing exact
      navigation of the needle. After placement of the needle into the renal pelvis,
      the nephrostomy tube was inserted by means of the Seldinger technique. RESULTS:
      The puncture procedure was successfully performed in each case. The renal pelvis
      was punctured in a single attempt in 10 of 12 cases. In two cases, multiple
      attempts were necessary because bending of the puncture needle led to
      inaccuracies of the navigation system. With exception of two small perirenal
      urinomas, no complications were seen. CONCLUSIONS: The magnetic field-based
      navigation device allows easy and accurate performance of nephrostomy guided
      solely by US.

PMID- 11340144
TI  - Treatment of type II endoleaks with Onyx.
AB  - Endoleaks are defined as persistent perfusion of an abdominal aortic aneurysm
      (AAA) after endovascular stent-graft deployment. The authors describe their
      experience treating six endoleaks with the liquid embolic agent Onyx (ethylene
      vinyl-alcohol copolymer). Complete endoleak occlusion was achieved in five of six
      cases. Follow-up imaging has demonstrated decreased aneurysm diameter in all
      patients 7-29 weeks (mean = 19.2 weeks) after treatment.

PMID- 11340145
TI  - Thromboembolism complicating thrombin injection of femoral artery pseudoaneurysm:
      management with intraarterial thrombolysis.
AB  - Ultrasound (US)-guided compression of pseudoaneurysms is being rapidly replaced
      by US-guided percutaneous treatment with thrombin injection because of the less
      intensive nature of this procedure. Thromboembolism after percutaneous treatment
      with thrombin injection is rare and has been described in brachial artery
      pseudoaneurysms. These were managed with intravenous administration of heparin
      and surgical thrombectomy. In this report, the authors describe thromboembolic
      complication of thrombin injection after treatment of a femoral artery
      pseudoaneurysm. This was managed by intraarterial thrombolysis with use of
      recombinant tissue plasminogen activator (rt-PA) with resolution of all major
      occlusive changes. A lower dose of thrombin injection and frequent postprocedural
      monitoring of distal pulses is recommended.

PMID- 11340146
TI  - Balloon embolization of the internal iliac artery before aneurysm endograft
      deployment.
AB  - Six patients, ranging from 69 to 81 years of age, underwent iliac artery
      embolization with use of Detachable Silicon Balloons (DSB) 11-14 days before
      stent-graft repair of aneurysms. Balloons of 8.8-mm, 9.4-mm, and 9.9-mm sizes
      were used with 20-30 g of release force. Deployment difficulty was experienced in
      three cases. Five of six cases were successful, with the iliac artery remaining
      occluded at the time of endografting; one case required subsequent coil
      replacement. The average operative time for balloon embolization (75 min +/- 28)
      was shorter than that in 18 cases of coil embolization performed within the same
      time period (111 min +/- 105), but the difference was not significant (P = .21).
      Postoperatively, one patient (17%) reported buttock claudication after the
      procedure. Use of the DSB represents an alternative to use of coils for
      embolization of large and tortuous iliac arteries.

PMID- 11340147
TI  - Direct US-guided puncture of the innominate veins for central venous access.
AB  - Maintenance of functioning venous access is recognized as the Achilles heel of
      long-term hemodialysis treatment. In patients who require catheter-directed
      hemodialysis, the internal jugular veins are recognized as the optimal veins for
      insertion of dialysis catheters. When these sites are no longer available,
      alternative venous access sites are required. The authors describe two
      hemodialysis patients with limited access sites in whom hemodialysis catheters
      were successfully inserted directly into the innominate veins with use of
      ultrasound-guided punctures.

PMID- 11340148
TI  - Malignant esophagogastric junction obstruction: palliative treatment with an
      antireflux valve stent.
AB  - The authors assessed the efficacy of an antireflux valve stent in the palliation
      of malignant esophagogastric junction (EGJ) obstruction after in vitro testing of
      the stent. Seventeen patients with inoperable malignant EGJ obstruction were
      treated. Antireflux valves, made of three polyurethane leaflets, were attached to
      the distal part of the stent to prevent reflux. When the flow rate of normal
      saline was 100 mL/sec in the forward direction, the valve fully opened at a
      pressure of 10 mm Hg. When the flow rate of normal saline was 0.35 mL/sec in the
      backward direction, the valve nearly completely closed at a pressure of 10 mm Hg.
      Stent placement was successful in all patients without complications. The median
      dysphagia score decreased significantly, from 3.0 (dysphagia to liquids) to 1.0
      (dysphagia to normal solid food) (P < .0005). No patients experienced reflux
      symptoms. There was one case of stent migration. A valve stent that can prevent
      major reflux is an effective device for the palliation of malignant EGJ
      obstruction.

PMID- 11340149
TI  - SCVIR annual meeting film panel session: diagnosis and discussion of case 5.

PMID- 11340150
TI  - SCVIR annual meeting film panel session: diagnosis and discussion of case 6.

PMID- 11340151
TI  - SCVIR annual meeting film panel session: diagnosis and discussion of case 7.

PMID- 11340152
TI  - SCVIR annual meeting film panel session: diagnosis and discussion of case 8.

PMID- 11340153
TI  - Retrieval of fractured micropuncture wire from the groin.

PMID- 11340154
TI  - Flolan infusion interruption: a lethal complication during venous access.

PMID- 11340155
TI  - All in the family: the BTB/POZ, KRAB, and SCAN domains.

PMID- 11340156
TI  - Requirement for p27(KIP1) in retinoblastoma protein-mediated senescence.
AB  - In vivo and in vitro evidence indicate that cells do not divide indefinitely but
      instead stop growing and undergo a process termed cellular proliferative
      senescence. Very little is known about how senescence occurs, but there are
      several indications that the retinoblastoma protein (pRb) is involved, the most
      striking being that reintroduction of RB into RB(-/-) tumor cell lines induces
      senescence. In investigating the mechanism by which pRb induces senescence, we
      have found that pRb causes a posttranscriptional accumulation of the cyclin
      dependent kinase inhibitor p27(KIP1) that is accompanied by an increase in
      p27(KIP1) specifically bound to cyclin E and a concomitant decrease in cyclin E
      associated kinase activity. In contrast, pRb-related proteins p107 and p130,
      which also decrease cyclin E-kinase activity, do not cause an accumulation of
      p27(KIP1) and induce senescence poorly. In addition, the use of pRb proteins
      mutated in the pocket domain demonstrates that pRb upregulation of p27(KIP1) and
      senescence induction do not require the interaction of pRb with E2F. Furthermore,
      ectopic expression of p21(CIP1) or p27(KIP1) induces senescence but not the
      morphology change associated with pRb-mediated senescence, uncoupling senescence
      from the morphological transformation. Finally, the ability of pRb to maintain
      cell cycle arrest and induce senescence is reversibly abrogated by ablation of
      p27(KIP1) expression. These findings suggest that prolonged cell cycle arrest
      through the persistent and specific inhibition of cdk2 activity by p27(KIP1) is
      critical for pRb-induced senescence.

PMID- 11340157
TI  - Interaction of eukaryotic translation initiation factor 4G with the nuclear cap
      binding complex provides a link between nuclear and cytoplasmic functions of the
      m(7) guanosine cap.
AB  - In eukaryotes the majority of mRNAs have an m(7)G cap that is added
      cotranscriptionally and that plays an important role in many aspects of mRNA
      metabolism. The nuclear cap-binding complex (CBC; consisting of CBP20 and CBP80)
      mediates the stimulatory functions of the cap in pre-mRNA splicing, 3' end
      formation, and U snRNA export. As little is known about how nuclear CBC mediates
      the effects of the cap in higher eukaryotes, we have characterized proteins that
      interact with CBC in HeLa cell nuclear extracts as potential mediators of its
      function. Using cross-linking and coimmunoprecipitation, we show that eukaryotic
      translation initiation factor 4G (eIF4G), in addition to its function in the
      cytoplasm, is a nuclear CBC-interacting protein. We demonstrate that eIF4G
      interacts with CBC in vitro and that, in addition to its cytoplasmic
      localization, there is a significant nuclear pool of eIF4G in mammalian cells in
      vivo. Immunoprecipitation experiments suggest that, in contrast to the
      cytoplasmic pool, much of the nuclear eIF4G is not associated with eIF4E
      (translation cap binding protein of eIF4F) but is associated with CBC. While
      eIF4G stably associates with spliceosomes in vitro and shows close association
      with spliceosomal snRNPs and splicing factors in vivo, depletion studies show
      that it does not participate directly in the splicing reaction. Taken together
      the data indicate that nuclear eIF4G may be recruited to pre-mRNAs via its
      interaction with CBC and accompanies the mRNA to the cytoplasm, facilitating the
      switching of CBC for eIF4F. This may provide a mechanism to couple nuclear and
      cytoplasmic functions of the mRNA cap structure.

PMID- 11340158
TI  - The absence of the dna-dependent protein kinase catalytic subunit in mice results
      in anaphase bridges and in increased telomeric fusions with normal telomere
      length and G-strand overhang.
AB  - The major pathway in mammalian cells for repairing DNA double-strand breaks (DSB)
      is via nonhomologous end joining. Five components function in this pathway, of
      which three (Ku70, Ku80, and the DNA-dependent protein kinase catalytic subunit
      [DNA-PKcs]) constitute a complex termed DNA-dependent protein kinase (DNA-PK).
      Mammalian Ku proteins bind to DSB and recruit DNA-PKcs to the break.
      Interestingly, besides their role in DSB repair, Ku proteins bind to chromosome
      ends, or telomeres, protecting them from end-to-end fusions. Here we show that
      DNA-PKcs(-/-) cells display an increased frequency of spontaneous telomeric
      fusions and anaphase bridges. However, DNA-PKcs deficiency does not result in
      significant changes in telomere length or in deregulation of the G-strand
      overhang at the telomeres. Although less severe, this phenotype is reminiscent of
      the one recently described for Ku86-defective cells. Here we show that, besides
      DNA repair, a role for DNA-PKcs is to protect telomeres, which in turn are
      essential for chromosomal stability.

PMID- 11340159
TI  - p53 Stimulates TFIID-TFIIA-promoter complex assembly, and p53-T antigen complex
      inhibits TATA binding protein-TATA interaction.
AB  - Simian virus 40 large T antigen has been shown to inhibit p53-mediated
      transcription once tethered to p53-responsive promoters through interaction with
      p53. In this study we report that p53 stimulates transcription by enhancing the
      recruitment of the basal transcription factors, TFIIA and TFIID, on the promoter
      (the DA complex) and by inducing a conformational change in the DA complex.
      Significantly, we have demonstrated that T antigen inhibits p53-mediated
      transcription by blocking this ability of p53. We investigated the mechanism for
      this inhibition and found that DA complex formation was resistant to T-antigen
      repression when the TFIID-DNA complex was formed prior to addition of p53-T
      antigen complex, indicating that the T antigen, once tethered to the promoter by
      p53, targets TFIID. Further, we have shown that the p53-T antigen complex
      prevents the TATA binding protein from binding to the TATA box. Thus, these data
      suggest a detailed mechanism by which p53 activates transcription and by which T
      antigen inhibits p53-mediated transcription.

PMID- 11340160
TI  - Embryonic but not postnatal reexpression of hepatocyte nuclear factor 1alpha
      (HNF1alpha) can reactivate the silent phenylalanine hydroxylase gene in HNF1alpha
      deficient hepatocytes.
AB  - The failure to transcribe the phenylalanine hydroxylase (PAH) gene in the liver
      of hepatocyte nuclear factor 1alpha (HNF1alpha)-deficient mice correlated with
      DNA hypermethylation and the presence of an inactive chromatin structure (M.
      Pontoglio, D. M. Faust, A. Doyen, M. Yaniv, and M. C. Weiss, Mol. Cell. Biol.
      17:4948-4956, 1997). To evaluate the precise role played by HNF1alpha, DNA
      methylation, or histone acetylation in PAH gene silencing, we examined conditions
      that could restore PAH gene expression in HNF1alpha-deficient hepatocytes. We
      show that reactivation of PAH transcription can be achieved by reexpression of
      HNF1alpha in embryonic (i.e., embryonic day 12.5 [e12.5] to e13.5) hepatocytes
      but not in fetal (e17.5), newborn, and adult HNF1alpha-deficient hepatocytes.
      This defines a temporal competence window during which HNF1alpha can act to
      (re)program PAH gene transcription. We also show that PAH gene silencing can be
      partially relieved in HNF1alpha-deficient hepatocytes by treatment with the
      demethylating agent 5-azacytidine, even in the absence of HNF1alpha. Treatment
      using 5-azacytidine combined with trichostatin, a histone deacetylase inhibitor,
      resulted in a synergistic reactivation of the silenced PAH gene in adult
      hepatocytes, but this activity was not further increased by HNF1alpha
      reexpression. These results suggest that the HNF1alpha homeoprotein is involved
      in stage-specific developmental control of the methylation state and chromatin
      remodeling of the PAH gene.

PMID- 11340162
TI  - Cisplatin induces the proapoptotic conformation of Bak in a deltaMEKK1-dependent
      manner.
AB  - In a panel of four human melanoma cell lines, equitoxic doses of cisplatin
      induced the proapoptotic conformation of the Bcl-2 family protein Bak prior to
      the execution phase of apoptosis. Because cisplatin-induced modulation of the
      related Bax protein was seen in only one cell line, a degree of specificity in
      the signal to Bak is indicated. Little is known about upstream regulation of Bak
      activity. In this study, we examined whether the apoptosis-specific pathway
      mediated by a kinase fragment of MEKK1 (DeltaMEKK1) is involved in the observed
      Bak modulation. We report that expression of a kinase-inactive fragment of MEKK1
      (dominant negative MEKK [dnMEKK]) efficiently blocked cisplatin-induced
      modulation of Bak and cytochrome c release and consequently also reduced DEVDase
      activation and nuclear fragmentation. Accordingly, expression of a kinase-active
      MEKK1 fragment (dominant positive MEKK) was sufficient to induce modulation of
      Bak in three cell lines and to induce apoptosis in two of these. dnMEKK did not
      block cisplatin-induced c-Jun N-terminal kinase (JNK) activation, in agreement
      with a specifically proapoptotic role for the DeltaMEKK1 pathway. Finally, we
      show that reduction of Bak expression by antisense Bak reduced cisplatin-induced
      loss of mitochondrial integrity and caspase cleavage activity in breast cancer
      cell lines. In summary, we have identified Bak as a cisplatin-regulated component
      downstream in a proapoptotic, JNK-independent DeltaMEKK1 pathway.

PMID- 11340161
TI  - Cyclic AMP-mediated inhibition of cell growth requires the small G protein Rap1.
AB  - In many normal and transformed cell types, the intracellular second messenger
      cyclic AMP (cAMP) blocks the effects of growth factors and serum on mitogenesis,
      proliferation, and cell cycle progression. cAMP exerts these growth-inhibitory
      effects via inhibition of the mitogen-activated protein (MAP) kinase cascade.
      Here, using Hek293 and NIH 3T3 cells, we show that cAMP's inhibition of the MAP
      kinase cascade is mediated by the small G protein Rap1. Activation of Rap1 by
      cAMP induces the association of Rap1 with Raf-1 and limits Ras-dependent
      activation of ERK. In NIH 3T3 cells, Rap1 is required not only for cAMP's
      inhibition of ERK activation but for inhibition of cell proliferation and
      mitogenesis as well.

PMID- 11340163
TI  - A conserved cyclin-binding domain determines functional interplay between
      anaphase-promoting complex-Cdh1 and cyclin A-Cdk2 during cell cycle progression.
AB  - Periodic activity of the anaphase-promoting complex (APC) ubiquitin ligase
      determines progression through multiple cell cycle transitions by targeting cell
      cycle regulators for destruction. At the G(1)/S transition, phosphorylation
      dependent dissociation of the Cdh1-activating subunit inhibits the APC, allowing
      stabilization of proteins required for subsequent cell cycle progression. Cyclin
      dependent kinases (CDKs) that initiate and maintain Cdh1 phosphorylation have
      been identified. However, the issue of which cyclin-CDK complexes are involved
      has been a matter of debate, and the mechanism of how cyclin-CDKs interact with
      APC subunits remains unresolved. Here we substantiate the evidence that mammalian
      cyclin A-Cdk2 prevents unscheduled APC reactivation during S phase by
      demonstrating its periodic interaction with Cdh1 at the level of endogenous
      proteins. Moreover, we identified a conserved cyclin-binding motif within the
      Cdh1 WD-40 domain and show that its disruption abolished the Cdh1-cyclin A-Cdk2
      interaction, eliminated Cdh1-associated histone H1 kinase activity, and impaired
      Cdh1 phosphorylation by cyclin A-Cdk2 in vitro and in vivo. Overexpression of
      cyclin binding-deficient Cdh1 stabilized the APC-Cdh1 interaction and induced
      prolonged cell cycle arrest at the G(1)/S transition. Conversely, cyclin binding
      deficient Cdh1 lost its capability to support APC-dependent proteolysis of cyclin
      A but not that of other APC substrates such as cyclin B and securin Pds1.
      Collectively, these data provide a mechanistic explanation for the mutual
      functional interplay between cyclin A-Cdk2 and APC-Cdh1 and the first evidence
      that Cdh1 may activate the APC by binding specific substrates.

PMID- 11340164
TI  - Tissue-specific transgenic knockdown of Fos-related antigen 2 (Fra-2) expression
      mediated by dominant negative Fra-2.
AB  - Fos-related antigen 2 (Fra-2) is a member of the Fos family of immediate-early
      genes, most of which are rapidly induced by second messengers. All members of
      this family act by binding to AP-1 sites as heterodimeric complexes with other
      proteins. However, each appears to have a distinct role. The role and biology of
      Fra-2 are less well understood than those of its relatives c-Fos, Fra-1, and
      FosB; moreover, Fra-2 target genes remain largely unknown, as does the basis of
      its selective effects on transcriptional activity. To pursue these issues, we
      created a transgenic rat line (NATDNF2) in which a dominant negative fra-2 (DNF2)
      gene is strongly expressed in the pineal gland; tissue selectivity was achieved
      by putting the DNF2 gene under the control of the rat arylalkylamine N
      acetyltransferase (AANAT) regulatory region, which targets gene expression to a
      very restricted set of tissues (pineal gland >> retina). Expression of AANAT is
      normally turned on after the onset of darkness in the rat; as a result, pineal
      DNF2 expression occurs only at night. This was associated with marked suppression
      of the nocturnal increase in fra-2 mRNA and protein levels, indicating that DNF2
      expression inhibits downstream effects of Fra-2, including the maintenance of
      high levels of fra-2 gene expression. Analysis of 1,190 genes in the NATDNF2
      pineal gland, including the AANAT gene, identified two whose expression is
      strongly linked to fra-2 expression: the genes encoding type II iodothyronine
      deiodinase and nectadrin (CD24).

PMID- 11340165
TI  - Xbp1-mediated repression of CLB gene expression contributes to the modifications
      of yeast cell morphology and cell cycle seen during nitrogen-limited growth.
AB  - Yeast cells undergo morphological transformations in response to diverse
      environmental signals. One such event, called pseudohyphal differentiation,
      occurs when diploid yeast cells are partially starved for nitrogen on a solid
      agar medium. The nitrogen-starved cells elongate, and a small fraction form
      filaments that penetrate the agar surface. The molecular basis for the changes in
      cell morphology and cell cycle in response to nitrogen limitation are poorly
      defined, in part because the heterogeneous growth states of partially starved
      cells on agar media are not amenable to biochemical analysis. In this work, we
      used chemostat cultures to study the role of cell cycle regulators with respect
      to yeast differentiation in response to nitrogen limitation under controlled,
      homogeneous culture conditions. We found that Clb1, Clb2, and Clb5 cyclin levels
      are reduced in nitrogen-limited chemostat cultures compared to levels in rich
      medium cultures, whereas the Xbp1 transcriptional repressor is highly induced
      under these conditions. Furthermore, the deletion of XBP1 prevents the drop in
      Clb2 levels and inhibits cellular elongation in nitrogen-limited chemostat
      cultures as well as inhibiting pseudohyphal growth on nitrogen-limited agar
      media. Deletion of the CLB2 gene restores an elongated morphology and
      filamentation to the xbp1Delta mutant in response to nitrogen limitation.
      Transcriptional activation of the XBP1 gene and the subsequent repression of CLB
      gene expression are thus key responses of yeast cells to nitrogen limitation.

PMID- 11340166
TI  - Rfc4 interacts with Rpa1 and is required for both DNA replication and DNA damage
      checkpoints in Saccharomyces cerevisiae.
AB  - The large subunit of replication protein A (Rpa1) consists of three single
      stranded DNA binding domains and an N-terminal domain (Rpa1N) of unknown
      function. To determine the essential role of this domain we searched for
      mutations that require wild-type Rpa1N for viability in yeast. A mutation in
      RFC4, encoding a small subunit of replication factor C (RFC), was found to
      display allele-specific interactions with mutations in the gene encoding Rpa1
      (RFA1). Mutations that map to Rpa1N and confer sensitivity to the DNA synthesis
      inhibitor hydroxyurea, such as rfa1-t11, are lethal in combination with rfc4-2.
      The rfc4-2 mutant itself is sensitive to hydroxyurea, and like rfc2 and rfc5
      strains, it exhibits defects in the DNA replication block and intra-S
      checkpoints. RFC4 and the DNA damage checkpoint gene RAD24 were found to be
      epistatic with respect to DNA damage sensitivity. We show that the rfc4-2 mutant
      is defective in the G(1)/S DNA damage checkpoint response and that both the rfc4
      2 and rfa1-t11 strains are defective in the G(2)/M DNA damage checkpoint. Thus,
      in addition to its essential role as part of the clamp loader in DNA replication,
      Rfc4 plays a role as a sensor in multiple DNA checkpoint pathways. Our results
      suggest that a physical interaction between Rfc4 and Rpa1N is required for both
      roles.

PMID- 11340167
TI  - Pgc-1-related coactivator, a novel, serum-inducible coactivator of nuclear
      respiratory factor 1-dependent transcription in mammalian cells.
AB  - The thermogenic peroxisome proliferator-activated receptor gamma (PPAR-gamma)
      coactivator 1 (PGC-1) has previously been shown to activate mitochondrial
      biogenesis in part through a direct interaction with nuclear respiratory factor 1
      (NRF-1). In order to identify related coactivators that act through NRF-1, we
      searched the databases for sequences with similarities to PGC-1. Here, we
      describe the first characterization of a 177-kDa transcriptional coactivator,
      designated PGC-1-related coactivator (PRC). PRC is ubiquitously expressed in
      murine and human tissues and cell lines; but unlike PGC-1, PRC was not
      dramatically up-regulated during thermogenesis in brown fat. However, its
      expression was down-regulated in quiescent BALB/3T3 cells and was rapidly induced
      by reintroduction of serum, conditions where PGC-1 was not detected. PRC
      activated NRF-1-dependent promoters in a manner similar to that observed for PGC
      1. Moreover, NRF-1 was immunoprecipitated from cell extracts by antibodies
      directed against PRC, and both proteins were colocalized to the nucleoplasm by
      confocal laser scanning microscopy. PRC interacts in vitro with the NRF-1 DNA
      binding domain through two distinct recognition motifs that are separated by an
      unstructured proline-rich region. PRC also contains a potent transcriptional
      activation domain in its amino terminus adjacent to an LXXLL motif. The spatial
      arrangement of these functional domains coincides with those found in PGC-1,
      supporting the conclusion that PRC and PGC-1 are structurally and functionally
      related. We conclude that PRC is a functional relative of PGC-1 that operates
      through NRF-1 and possibly other activators in response to proliferative signals.

PMID- 11340168
TI  - Activation of the Ral and phosphatidylinositol 3' kinase signaling pathways by
      the ras-related protein TC21.
AB  - TC21 is a member of the Ras superfamily of small GTP-binding proteins that, like
      Ras, has been implicated in the regulation of growth-stimulating pathways. We
      have previously identified the Raf/mitogen-activated protein kinase pathway as a
      direct TC21 effector pathway required for TC21-induced transformation (M.
      Rosario, H. F. Paterson, and C. J. Marshall, EMBO J. 18:1270-1279, 1999). In this
      study we have identified two further effector pathways for TC21, which contribute
      to TC21-stimulated transformation: the phosphatidylinositol 3' kinase (PI-3K) and
      Ral signaling pathways. Expression of constitutively active TC21 leads to the
      activation of Ral A and the PI-3K-dependent activation of Akt/protein kinase B.
      Strong activation of the PI-3K/Akt pathway is seen even with very low levels of
      TC21 expression, suggesting that TC21 may be a key small GTPase-regulator of PI
      3K. TC21-induced alterations in cellular morphology in NIH 3T3 and PC12 cells are
      also PI-3K dependent. On the other hand, activation of the Ral pathway by TC21 is
      required for TC21-stimulated DNA synthesis but not transformed morphology. We
      show that inhibition of Ral signaling blocks DNA synthesis in human tumor cell
      lines containing activating mutations in TC21, demonstrating for the first time
      that this pathway is required for the proliferation of human tumor cells.
      Finally, we provide mechanisms for the activation of these pathways, namely, the
      direct in vivo interaction of TC21 with guanine nucleotide exchange factors for
      Ral, resulting in their translocation to the plasma membrane, and the direct
      interaction of TC21 with PI-3K. In both cases, the effector domain region of TC21
      is required since point mutations in this region can interfere with activation of
      downstream signaling.

PMID- 11340169
TI  - Vav1 regulates phospholipase cgamma activation and calcium responses in mast
      cells.
AB  - The hematopoietic cell-specific protein Vav1 is a substrate of tyrosine kinases
      activated following engagement of many receptors, including FcepsilonRI. Vav1
      deficient mice contain normal numbers of mast cells but respond more weakly than
      their normal counterparts to a passive systemic anaphylaxis challenge. Vav1
      deficient bone marrow-derived mast cells also exhibited reduced degranulation and
      cytokine production, although tyrosine phosphorylation of FcepsilonRI, Syk, and
      LAT (linker for activation of T cells) was normal. In contrast, tyrosine
      phosphorylation of phospholipase Cgamma1 (PLCgamma1) and PLCgamma2 and calcium
      mobilization were markedly inhibited. Reconstitution of deficient mast cells with
      Vav1 restored normal tyrosine phosphorylation of PLCgamma1 and PLCgamma2 and
      calcium responses. Thus, Vav1 is essential to FcepsilonRI-mediated activation of
      PLCgamma and calcium mobilization in mast cells. In addition to its known role as
      an activator of Rac1 GTPases, these findings demonstrate a novel function for
      Vav1 as a regulator of PLCgamma-activated calcium signals.

PMID- 11340170
TI  - Mutations in the novel membrane protein spinster interfere with programmed cell
      death and cause neural degeneration in Drosophila melanogaster.
AB  - Mutations in the spin gene are characterized by an extraordinarily strong
      rejection behavior of female flies in response to male courtship. They are also
      accompanied by decreases in the viability, adult life span, and oviposition rate
      of the flies. In spin mutants, some oocytes and adult neural cells undergo
      degeneration, which is preceded by reductions in programmed cell death of nurse
      cells in ovaries and of neurons in the pupal nervous system, respectively. The
      central nervous system (CNS) of spin mutant flies accumulates autofluorescent
      lipopigments with characteristics similar to those of lipofuscin. The spin locus
      generates at least five different transcripts, with only two of these being able
      to rescue the spin behavioral phenotype; each encodes a protein with multiple
      membrane-spanning domains that are expressed in both the surface glial cells in
      the CNS and the follicle cells in the ovaries. Orthologs of the spin gene have
      also been identified in a number of species from nematodes to humans. Analysis of
      the spin mutant will give us new insights into neurodegenerative diseases and
      aging.

PMID- 11340171
TI  - c-Myc is a critical target for c/EBPalpha in granulopoiesis.
AB  - CCAAT/enhancer binding protein alpha (C/EBPalpha) is an integral factor in the
      granulocytic developmental pathway, as myeloblasts from C/EBPalpha-null mice
      exhibit an early block in differentiation. Since mice deficient for known
      C/EBPalpha target genes do not exhibit the same block in granulocyte maturation,
      we sought to identify additional C/EBPalpha target genes essential for myeloid
      cell development. To identify such genes, we used both representational
      difference analysis and oligonucleotide array analysis with RNA derived from a
      C/EBPalpha-inducible myeloid cell line. From each of these independent screens,
      we identified c-Myc as a C/EBPalpha negatively regulated gene. We mapped an E2F
      binding site in the c-Myc promoter as the cis-acting element critical for
      C/EBPalpha negative regulation. The identification of c-Myc as a C/EBPalpha
      target gene is intriguing, as it has been previously shown that down-regulation
      of c-Myc can induce myeloid differentiation. Here we show that stable expression
      of c-Myc from an exogenous promoter not responsive to C/EBPalpha-mediated down
      regulation forces myeloblasts to remain in an undifferentiated state. Therefore,
      C/EBPalpha negative regulation of c-Myc is critical for allowing early myeloid
      precursors to enter a differentiation pathway. This is the first report to
      demonstrate that C/EBPalpha directly affects the level of c-Myc expression and,
      thus, the decision of myeloid blasts to enter into the granulocytic
      differentiation pathway.

PMID- 11340172
TI  - Loss of hippocampal CA3 pyramidal neurons in mice lacking STAM1.
AB  - STAM1, a member of the STAM (signal transducing adapter molecule) family, has a
      unique structure containing a Src homology 3 domain and ITAM (immunoreceptor
      tyrosine-based activation motif). STAM1 was previously shown to be associated
      with the Jak2 and Jak3 tyrosine kinases and to be involved in the regulation of
      intracellular signal transduction mediated by interleukin-2 (IL-2) and
      granulocyte-macrophage colony-stimulating factor (GM-CSF) in vitro. Here we
      generated mice lacking STAM1 by using homologous recombination with embryonic
      stem cells. STAM1(-/-) mice were morphologically indistinguishable from their
      littermates at birth. However, growth retardation in the third week after birth
      was observed for the STAM1(-/-) mice. Unexpectedly, despite the absence of STAM1,
      hematopoietic cells, including T- and B-lymphocyte and other hematopoietic cell
      populations, developed normally and responded well to several cytokines,
      including IL-2 and GM-CSF. However, histological analyses revealed the
      disappearance of hippocampal CA3 pyramidal neurons in STAM1(-/-) mice.
      Furthermore, we observed that primary hippocampal neurons derived from STAM1(-/-)
      mice are vulnerable to cell death induced by excitotoxic amino acids or an NO
      donor. These data suggest that STAM1 is dispensable for cytokine-mediated
      signaling in lymphocytes but may be involved in the survival of hippocampal CA3
      pyramidal neurons.

PMID- 11340173
TI  - Loss of HCF-1-chromatin association precedes temperature-induced growth arrest of
      tsBN67 cells.
AB  - Human HCF-1 is a large, highly conserved, and abundant nuclear protein that plays
      an important but unknown role in cell proliferation. It also plays a role in
      activation of herpes simplex virus immediate-early gene transcription by the
      viral regulatory protein VP16. A single proline-to-serine substitution in the HCF
      1 VP16 interaction domain causes a temperature-induced arrest of cell
      proliferation in hamster tsBN67 cells and prevents transcriptional activation by
      VP16. We show here that HCF-1 is naturally bound to chromatin in uninfected cells
      through its VP16 interaction domain. HCF-1 is chromatin bound in tsBN67 cells at
      permissive temperature but dissociates from chromatin before tsBN67 cells stop
      proliferating at the nonpermissive temperature, suggesting that loss of HCF-1
      chromatin association is the primary cause of the temperature-induced tsBN67 cell
      proliferation arrest. We propose that the role of HCF-1 in cell proliferation is
      to regulate gene transcription by associating with a multiplicity of DNA-bound
      transcription factors through its VP16 interaction domain.

PMID- 11340174
TI  - Poly(dA-dT) promoter elements increase the equilibrium accessibility of
      nucleosomal DNA target sites.
AB  - Polypurine tracts are important elements of eukaryotic promoters. They are
      believed to somehow destabilize chromatin, but the mechanism of their action is
      not known. We show that incorporating an A(16) element at an end of the
      nucleosomal DNA and further inward destabilizes histone-DNA interactions by 0.1
      +/- 0.03 and 0.35 +/- 0.04 kcal mol(-1), respectively, and is accompanied by 1.5-
      +/- 0.1-fold and 1.7- +/- 0.1-fold increases in position-averaged equilibrium
      accessibility of nucleosomal DNA target sites. These effects are comparable in
      magnitude to effects of A(16) elements that correlate with transcription in vivo,
      suggesting that our system may capture most of their physiological role. These
      results point to two distinct but interrelated models for the mechanism of action
      of polypurine tract promoter elements in vivo. Given a nucleosome positioned over
      a promoter region, the presence of a polypurine tract in that nucleosome's DNA
      decreases the stability of the DNA wrapping, increasing the equilibrium
      accessibility of other DNA target sites buried inside that nucleosome.
      Alternatively (if nucleosomes are freely mobile), the presence of a polypurine
      tract provides a free energy bias for the nucleosome to move to alternative
      locations, thereby changing the equilibrium accessibilities of other nearby DNA
      target sites.

PMID- 11340175
TI  - Selective inhibition of selenocysteine tRNA maturation and selenoprotein
      synthesis in transgenic mice expressing isopentenyladenosine-deficient
      selenocysteine tRNA.
AB  - Selenocysteine (Sec) tRNA (tRNA([Ser]Sec)) serves as both the site of Sec
      biosynthesis and the adapter molecule for donation of this amino acid to protein.
      The consequences on selenoprotein biosynthesis of overexpressing either the wild
      type or a mutant tRNA([Ser]Sec) lacking the modified base, isopentenyladenosine,
      in its anticodon loop were examined by introducing multiple copies of the
      corresponding tRNA([Ser]Sec) genes into the mouse genome. Overexpression of wild
      type tRNA([Ser]Sec) did not affect selenoprotein synthesis. In contrast, the
      levels of numerous selenoproteins decreased in mice expressing
      isopentenyladenosine-deficient (i(6)A(-)) tRNA([Ser]Sec) in a protein- and tissue
      specific manner. Cytosolic glutathione peroxidase and mitochondrial thioredoxin
      reductase 3 were the most and least affected selenoproteins, while selenoprotein
      expression was most and least affected in the liver and testes, respectively. The
      defect in selenoprotein expression occurred at translation, since selenoprotein
      mRNA levels were largely unaffected. Analysis of the tRNA([Ser]Sec) population
      showed that expression of i(6)A(-) tRNA([Ser]Sec) altered the distribution of the
      two major isoforms, whereby the maturation of tRNA([Ser]Sec) by methylation of
      the nucleoside in the wobble position was repressed. The data suggest that the
      levels of i(6)A(-) tRNA([Ser]Sec) and wild-type tRNA([Ser]Sec) are regulated
      independently and that the amount of wild-type tRNA([Ser]Sec) is determined, at
      least in part, by a feedback mechanism governed by the level of the
      tRNA([Ser]Sec) population. This study marks the first example of transgenic mice
      engineered to contain functional tRNA transgenes and suggests that i(6)A(-)
      tRNA([Ser]Sec) transgenic mice will be useful in assessing the biological roles
      of selenoproteins.

PMID- 11340176
TI  - A calcium-regulated gatekeeper in phloem sieve tubes.

PMID- 11340177
TI  - slender rice, a constitutive gibberellin response mutant, is caused by a null
      mutation of the SLR1 gene, an ortholog of the height-regulating gene
      GAI/RGA/RHT/D8.
AB  - The rice slender mutant (slr1-1) is caused by a single recessive mutation and
      results in a constitutive gibberellin (GA) response phenotype. The mutant
      elongates as if saturated with GAs. In this mutant, (1) elongation was unaffected
      by an inhibitor of GA biosynthesis, (2) GA-inducible alpha-amylase was produced
      by the aleurone layers without gibberellic acid application, and (3) endogenous
      GA content was lower than in the wild-type plant. These results indicate that the
      product of the SLR1 gene is an intermediate of the GA signal transduction
      pathway. SLR1 maps to OsGAI in rice and has significant homology with height
      regulating genes, such as RHT-1Da in wheat, D8 in maize, and GAI and RGA in
      Arabidopsis. The GAI gene family is likely to encode transcriptional factors
      belonging to the GRAS gene superfamily. DNA sequence analysis revealed that the
      slr1-1 mutation is a single basepair deletion of the nuclear localization signal
      domain, resulting in a frameshift mutation that abolishes protein production.
      Furthermore, introduction of a 6-kb genomic DNA fragment containing the wild-type
      SLR1 gene into the slr1-1 mutant restored GA sensitivity to normal. These results
      indicate that the slr1-1 mutant is caused by a loss-of-function mutation of the
      SLR1 gene, which is an ortholog of GAI, RGA, RHT, and D8. We also succeeded in
      producing GA-insensitive dwarf rice by transforming wild-type rice with a
      modified SLR1 gene construct that has a 17-amino acid deletion affecting the
      DELLA region. Thus, we demonstrate opposite GA response phenotypes depending on
      the type of mutations in SLR1.

PMID- 11340178
TI  - early bolting in short days: an Arabidopsis mutation that causes early flowering
      and partially suppresses the floral phenotype of leafy.
AB  - The time of flowering in Arabidopsis is controlled by multiple endogenous and
      environmental signals. Some of these signals promote the onset of flowering,
      whereas others repress it. We describe here the isolation and characterization of
      two allelic mutations that cause early flowering and define a new locus, EARLY
      BOLTING IN SHORT DAYS (EBS). Acceleration of flowering time in the ebs mutants is
      especially conspicuous under short-day photoperiods and results from a reduction
      of the adult vegetative phase of the plants. In addition to the early flowering
      phenotype, ebs mutants show a reduction in seed dormancy, plant size, and
      fertility. Double mutant analysis with gibberellin-deficient mutants indicates
      that both the early-flowering and the precocious-germination phenotypes require
      gibberellin biosynthesis. Analysis of the genetic interactions among ebs and
      several mutations causing late flowering shows that the ft mutant phenotype is
      epistatic over the early flowering of ebs mutants, suggesting that the precocious
      flowering of ebs requires the FT gene product. Finally, the ebs mutation causes
      an increase in the level of expression of the floral homeotic genes APETALA3
      (AP3), PISTILLATA (PI), and AGAMOUS (AG) and partially rescues the mutant floral
      phenotype of leafy-6 (lfy-6) mutants. These results suggest that EBS participates
      as a negative regulator in developmental processes such as germination, flowering
      induction, and flower organ specification.

PMID- 11340179
TI  - The Arabidopsis mutant cev1 has constitutively active jasmonate and ethylene
      signal pathways and enhanced resistance to pathogens.
AB  - Jasmonates (JAs) inhibit plant growth and induce plant defense responses. To
      define genes in the Arabidopsis JA signal pathway, we screened for mutants with
      constitutive expression of a luciferase reporter for the JA-responsive promoter
      from the vegetative storage protein gene VSP1. One mutant, named constitutive
      expression of VSP1 (cev1), produced plants that were smaller than wild type, had
      stunted roots with long root hairs, accumulated anthocyanin, had constitutive
      expression of the defense-related genes VSP1, VSP2, Thi2.1, PDF1.2, and CHI-B,
      and had enhanced resistance to powdery mildew diseases. Genetic evidence
      indicated that the cev1 phenotype required both COI1, an essential component of
      the JA signal pathway, and ETR1, which encodes the ethylene receptor. We conclude
      that cev1 stimulates both the JA and the ethylene signal pathways and that CEV1
      regulates an early step in an Arabidopsis defense pathway.

PMID- 11340180
TI  - Overexpression of the tobacco Tsi1 gene encoding an EREBP/AP2-type transcription
      factor enhances resistance against pathogen attack and osmotic stress in tobacco.
AB  - Using mRNA differential display analysis, we isolated a salt-induced transcript
      that showed a significant sequence homology with an EREBP/AP2 DNA binding motif
      from oilseed rape plants. With this cDNA fragment as a probe, cDNA clone Tsi1
      (for Tobacco stress-induced gene1) was isolated from a tobacco cDNA library. RNA
      gel blot analysis indicated that transcripts homologous with Tsi1 were induced
      not only in NaCl-treated leaves but also in leaves treated with ethephon or
      salicylic acid. Transient expression analysis using a Tsi1::smGFP fusion gene in
      BY-2 cells indicated that the Tsi1 protein was targeted to the nucleus. Fusion
      protein of Tsi1 with GAL4 DNA binding domain strongly activated transcription in
      yeast, and the transactivating activity was localized to the 13 C-terminal amino
      acids of Tsi1. Electrophoretic mobility shift assays revealed that Tsi1 could
      bind specifically to the GCC and the DRE/CRT sequences, although the binding
      activity to the former was stronger than that to the latter. Furthermore,
      Agrobacterium-mediated transient expression and transgenic plants expressing Tsi1
      demonstrated that overexpression of the Tsi1 gene induced expression of several
      pathogenesis-related genes under normal conditions, resulting in improved
      tolerance to salt and pathogens. These results suggest that Tsi1 might be
      involved as a positive trans-acting factor in two separate signal transduction
      pathways under abiotic and biotic stress.

PMID- 11340181
TI  - Identification of Arabidopsis histone deacetylase HDA6 mutants that affect
      transgene expression.
AB  - A mutant screen was conducted in Arabidopsis that was based on deregulated
      expression of auxin-responsive transgenes. Two different tightly regulated (i.e.,
      very low expression in the absence of auxin treatment and very high expression
      after exogenous auxin treatment) auxin-responsive promoters were used to drive
      the expression of both a beta-glucuronidase (GUS) reporter gene and a hygromycin
      phosphotransferase (HPH)-selectable marker gene. This screen yielded several
      mutants, and five of the mutations (axe1-1 to axe1-5) mapped to the same locus on
      chromosome 5. A map-based cloning approach was used to locate the axe1 mutations
      in an Arabidopsis RPD3-like histone deacetylase gene, referred to as HDA6. The
      axe1 mutant plants displayed increased expression of the GUS and HPH transgenes
      in the absence of auxin treatment and increased auxin-inducible expression of the
      transgenes compared with nonmutant control plants. None of a variety of
      endogenous, natural auxin-inducible genes in the mutant plants were upregulated
      like the transgenes, however. Results of treatment with the DNA methylation
      inhibitor 5-aza-2'-deoxycytidine suggest that the axe1 mutations affect transgene
      silencing; however, histone deacetylase inhibitors had no affect on transgene
      silencing in mutant or control plants. The specific effect of AtHDA6 mutations on
      the auxin-responsive transgenes implicates this RPD3-like histone deacetylase as
      playing a role in transgene silencing. Furthermore, the effect of AtHDA6 on
      transgene silencing may be independent of its histone deacetylase activity.

PMID- 11340182
TI  - Mitochondrial aldehyde dehydrogenase activity is required for male fertility in
      maize.
AB  - Some plant cytoplasms express novel mitochondrial genes that cause male
      sterility. Nuclear genes that disrupt the accumulation of the corresponding
      mitochondrial gene products can restore fertility to such plants. The Texas (T)
      cytoplasm mitochondrial genome of maize expresses a novel protein, URF13, which
      is necessary for T cytoplasm-induced male sterility. Working in concert,
      functional alleles of two nuclear genes, rf1 and rf2, can restore fertility to T
      cytoplasm plants. Rf1 alleles, but not Rf2 alleles, reduce the accumulation of
      URF13. Hence, Rf2 differs from typical nuclear restorers in that it does not
      alter the accumulation of the mitochondrial protein necessary for T cytoplasm
      induced male sterility. This study established that the rf2 gene encodes a
      soluble protein that accumulates in the mitochondrial matrix. Three independent
      lines of evidence establish that the RF2 protein is an aldehyde dehydrogenase
      (ALDH). The finding that T cytoplasm plants that are homozygous for the rf2-R213
      allele are male sterile but accumulate normal amounts of RF2 protein that lacks
      normal mitochondrial (mt) ALDH activity provides strong evidence that rf2-encoded
      mtALDH activity is required to restore male fertility to T cytoplasm maize.
      Detailed genetic analyses have established that the rf2 gene also is required for
      anther development in normal cytoplasm maize. Hence, it appears that the rf2 gene
      was recruited recently to function as a nuclear restorer. ALDHs typically have
      very broad substrate specificities. Indeed, the RF2 protein is capable of
      oxidizing at least three aldehydes. Hence, the specific metabolic pathway(s)
      within which the rf2-encoded mtALDH acts remains to be discovered.

PMID- 11340183
TI  - A harpin binding site in tobacco plasma membranes mediates activation of the
      pathogenesis-related gene HIN1 independent of extracellular calcium but dependent
      on mitogen-activated protein kinase activity.
AB  - Harpin from the bean halo-blight pathogen Pseudomonas syringae pv phaseolicola
      (harpin(Psph)) elicits the hypersensitive response and the accumulation of
      pathogenesis-related gene transcripts in the nonhost plant tobacco. Here, we
      report the characterization of a nonproteinaceous binding site for harpin(Psph)
      in tobacco plasma membranes, which is assumed to mediate the activation of plant
      defense responses in a receptor-like manner. Binding of 125I-harpin(Psph) to
      tobacco microsomal membranes (dissociation constant = 425 nM) and protoplasts
      (dissociation constant = 380 nM) was specific, reversible, and saturable. A close
      correlation was found between the abilities of harpin(Psph) fragments to elicit
      the transcript accumulation of the pathogenesis-related tobacco gene HIN1 and to
      compete for binding of 125I-harpin(Psph) to its binding site. Another elicitor of
      the hypersensitive response and HIN1 induction in tobacco, the Phytophthora
      megasperma-derived beta-elicitin beta-megaspermin, failed to bind to the putative
      harpin(Psph) receptor. In contrast to activation by beta-megaspermin,
      harpin(Psph)-induced activation of the 48-kD salicylic acid-responsive mitogen
      activated protein kinase (MAPK) and HIN1 transcript accumulation were independent
      of extracellular calcium. Moreover, use of the MAPK kinase inhibitor U0126
      revealed that MAPK activity was essential for pathogenesis-related gene
      expression in harpin(Psph)-treated tobacco cells. Thus, a receptor-mediated MAPK
      dependent signaling pathway may mediate the activation of plant defense responses
      induced by harpin(Psph).

PMID- 11340184
TI  - A plant plasma membrane ATP binding cassette-type transporter is involved in
      antifungal terpenoid secretion.
AB  - ATP binding cassette (ABC) transporters, which are found in all species, are
      known mainly for their ability to confer drug resistance. To date, most of the
      ABC transporters characterized in plants have been localized in the vacuolar
      membrane and are considered to be involved in the intracellular sequestration of
      cytotoxins. Working on the assumption that certain ABC transporters might be
      involved in defense metabolite secretion and their expression might be regulated
      by the concentration of these metabolites, we treated a Nicotiana plumbaginifolia
      cell culture with sclareolide, a close analog of sclareol, an antifungal
      diterpene produced at the leaf surface of Nicotiana spp; this resulted in the
      appearance of a 160-kD plasma membrane protein, which was partially sequenced.
      The corresponding cDNA (NpABC1) was cloned and shown to encode an ABC
      transporter. In vitro and in situ immunodetection showed NpABC1 to be localized
      in the plasma membrane. Under normal conditions, expression was found in the leaf
      epidermis. In cell culture and in leaf tissues, NpABC1 expression was strongly
      enhanced by sclareolide and sclareol. In parallel with NpABC1 induction, cells
      acquired the ability to excrete a labeled synthetic sclareolide derivative. These
      data suggest that NpABC1 is involved in the secretion of a secondary metabolite
      that plays a role in plant defense.

PMID- 11340185
TI  - Influence of KDEL on the fate of trimeric or assembly-defective phaseolin:
      selective use of an alternative route to vacuoles.
AB  - The tetrapeptide KDEL is commonly found at the C terminus of soluble proteins of
      the endoplasmic reticulum (ER), and it contributes to their localization by
      interacting with a receptor that recycles between the Golgi complex and the ER.
      We investigated the effects of the addition of KDEL to phaseolin, a protein
      normally delivered from the ER to storage vacuoles via the Golgi complex. We show
      that KDEL prevents acquisition of trans-Golgi-specific glycan modifications and
      causes interactions with the chaperone BiP that are distinct from the ones
      between BiP and defective proteins. KDEL markedly increases the stability of
      phaseolin, but a small proportion of phaseolin-KDEL slowly reaches the vacuole
      without undergoing Golgi-mediated glycan modifications, in a process that can be
      inhibited by brefeldin A but not monensin. Our results indicate that KDEL can
      operate with high efficiency before proteins can reach the late Golgi cisternae
      but allows or promotes delivery to vacuoles via an alternative mechanism.
      However, addition of KDEL does not alter the destiny of an assembly-defective
      form of phaseolin, suggesting that the plant ER quality control mechanism is
      dominant over KDEL effects.

PMID- 11340186
TI  - Sucrose export defective1 encodes a novel protein implicated in chloroplast-to
      nucleus signaling.
AB  - The Sucrose export defective1 (Sxd1) gene of maize was cloned and shown to encode
      a novel protein conserved between plants and cyanobacteria. The structure of the
      Sxd1 locus was determined in wild-type plants and two independent sxd1 alleles.
      Expression analysis demonstrated that the gene was transcribed in all green
      tissues, with highest levels in maturing leaf blades. In situ hybridization
      studies revealed high levels of Sxd1 mRNA in bundle sheath cells, with lower
      levels within the mesophyll. The SXD1 protein was localized to chloroplasts, in
      both bundle sheath and mesophyll cells. Levels of sucrose, glucose, and fructose
      were compared between wild-type and sxd1 plants. Mutant plants were fully capable
      of producing sucrose and accumulated all three sugars at concentrations above
      those measured in wild-type plants. Despite these increased sugar concentrations,
      photosynthetic gene expression was not significantly downregulated in affected
      areas of sxd1 leaf blades. These results are consistent with photosynthate being
      trapped within anthocyanin-accumulating regions of sxd1 leaves due to
      plasmodesmal occlusion at the bundle sheath-vascular parenchyma boundary of the
      minor veins. A model for SXD1 function is proposed in which the protein is
      involved in a chloroplast-to-nucleus signaling pathway necessary for proper late
      stage differentiation of maize bundle sheath cells, including the developmentally
      regulated modification of plasmodesmata.

PMID- 11340187
TI  - Arabidopsis PLC1 is required for secondary responses to abscisic acid signals.
AB  - The role of inositol 1,4,5-trisphosphate (Ins[1,4,5]P3) in transducing the
      abscisic acid (ABA) signal during seed germination and in the stress responses of
      mature plants is poorly understood. We have considered the contributions of the
      phospholipase C1 (encoded by AtPLC1) and an Ins(1,4,5)P3 5-phosphatase (encoded
      by AtIP5PII) to ABA signaling by using a modified version of the glucocorticoid
      inducible system to regulate transgene expression. In the presence of the
      dexamethasone (Dex) inducer, transgenic lines expressing the AtPLC1 antisense and
      AtIP5PII sense transgenes showed no inhibition of germination and growth by ABA,
      whereas in the absence of the inducer they were sensitive. In the presence of
      Dex, these lines accumulated lower Ins(1,4,5)P3 levels upon ABA treatment
      compared with that of the control transgenic lines. RNA gel blot analysis
      revealed a decrease in the induction of the ABA-responsive genes RD29a, KIN2, and
      RD22 but not COR47 in the Dex-induced transgenic plants. In transgenic lines
      expressing the inducible AtPLC1 sense transgene, an increase in AtPLC1 expression
      was not sufficient to activate the expression of ABA-responsive genes in
      vegetative tissues. In vitro experiments demonstrated the induced PLC1 expression
      when extracts were assayed in the presence of calcium, but no increase in
      Ins(1,4,5)P3 levels in vivo was detected, suggesting that the PLC1 enzyme was
      latent. Our results indicate that although an increase in PLC1 activity and
      increased Ins(1,4,5)P3 levels are necessary for maximal gene induction by ABA,
      overexpression of AtPLC1 itself is not sufficient to trigger the expression of
      ABA-responsive genes. We propose that AtPLC1 plays a role in secondary ABA
      responses.

PMID- 11340188
TI  - Both the extracellular leucine-rich repeat domain and the kinase activity of FSL2
      are required for flagellin binding and signaling in Arabidopsis.
AB  - In Arabidopsis, activation of defense responses by flagellin is triggered by the
      specific recognition of the most conserved domain of flagellin, represented by
      the peptide flg22, in a process involving the FLS2 gene, which encodes a leucine
      rich repeat serine/threonine protein kinase. We show here that the two fls2
      mutant alleles, fls2-24 and fls2-17, which were shown previously to confer
      insensitivity to flg22, also cause impaired flagellin binding. These features are
      rescued when a functional FLS2 gene is expressed as a transgene in each of the
      fls2 mutant plants, indicating that FLS2 is necessary for flagellin binding. The
      point mutation of the fls2-17 allele lies in the kinase domain. A kinase carrying
      this missense mutation lacked autophosphorylation activity when expressed in
      Escherichia coli. This indicates that kinase activity is required for binding and
      probably affects the stability of the flagellin receptor complex. We further show
      that overexpression of the kinase-associated protein phosphatase (KAPP) in
      Arabidopsis results in plants that are insensitive to flagellin treatment, and we
      show reduced flg22 binding in these plants. Furthermore, using the yeast two
      hybrid system, we show physical interaction of KAPP with the kinase domain of
      FLS2. These results suggest that KAPP functions as a negative regulator of the
      FLS2 signal transduction pathway and that the phosphorylation of FLS2 is
      necessary for proper binding and signaling of the flagellin receptor complex.

PMID- 11340189
TI  - Cosuppression of the alpha subunits of beta-conglycinin in transgenic soybean
      seeds induces the formation of endoplasmic reticulum-derived protein bodies.
AB  - The expression of the alpha and alpha' subunits of beta-conglycinin was
      suppressed by sequence-mediated gene silencing in transgenic soybean seed. The
      resulting seeds had similar total oil and protein content and ratio compared with
      the parent line. The decrease in beta-conglycinin protein was apparently
      compensated by an increased accumulation of glycinin. In addition, proglycinin,
      the precursor of glycinin, was detected as a prominent polypeptide band in the
      protein profile of the transgenic seed extract. Electron microscopic analysis and
      immunocytochemistry of maturing transgenic soybean seeds indicated that the
      process of storage protein accumulation was altered in the transgenic line. In
      normal soybeans, the storage proteins are deposited in pre-existing vacuoles by
      Golgi-derived vesicles. In contrast, in transgenic seed with reduced beta
      conglycinin levels, endoplasmic reticulum (ER)-derived vesicles were observed
      that resembled precursor accumulating-vesicles of pumpkin seeds and the protein
      bodies accumulated by cereal seeds. Their ER-derived membrane of the novel
      vesicles did not contain the protein storage vacuole tonoplast-specific protein
      alpha-TIP, and the sequestered polypeptides did not contain complex glycans,
      indicating a preGolgi and nonvacuolar nature. Glycinin was identified as a major
      component of these novel protein bodies and its diversion from normal storage
      protein trafficking appears to be related to the proglycinin buildup in the
      transgenic seed. The stable accumulation of proteins in a protein body
      compartment instead of vacuolar accumulation of proteins may provide an
      alternative intracellular site to sequester proteins when soybeans are used as
      protein factories.

PMID- 11340191
TI  - Antisense inhibition of the photosynthetic antenna proteins CP29 and CP26:
      implications for the mechanism of protective energy dissipation.
AB  - The specific roles of the chlorophyll a/b binding proteins CP29 and CP26 in light
      harvesting and energy dissipation within the photosynthetic apparatus have been
      investigated. Arabidopsis was transformed with antisense constructs against the
      genes encoding the CP29 or CP26 apoprotein, which gave rise to several transgenic
      lines with remarkably low amounts of the antisense target proteins. The decrease
      in the level of CP24 protein in the CP29 antisense lines indicates a physical
      interaction between these complexes. Analysis of chlorophyll fluorescence showed
      that removal of the proteins affected photosystem II function, probably as a
      result of changes in the organization of the light-harvesting antenna. However,
      whole plant measurements showed that overall photosynthetic rates were similar to
      those in the wild type. Both antisense lines were capable of the qE type of
      nonphotochemical fluorescence quenching, although there were minor changes in the
      capacity for quenching and in its induction kinetics. High-light-induced
      violaxanthin deepoxidation to zeaxanthin was not affected, although the pool size
      of these pigments was decreased slightly. We conclude that CP29 and CP26 are
      unlikely to be sites for nonphotochemical quenching.

PMID- 11340190
TI  - Small changes in the regulation of one Arabidopsis profilin isovariant, PRF1,
      alter seedling development.
AB  - Profilin (PRF) is a low-molecular-weight actin binding protein encoded by a
      diverse gene family in plants. Arabidopsis PRF1 transcripts are moderately well
      expressed in all vegetative organs. A regulatory mutant in PRF1, prf1-1, was
      isolated from a library of T-DNA insertions. The insertion disrupted the promoter
      region of PRF1 100 bp upstream from the transcriptional start site. Although
      steady state levels of PRF1 transcripts appeared normal in mature prf1-1 plants,
      the levels in young seedlings were only one-half those observed in wild type.
      Reactions with a PRF1 isovariant-specific monoclonal antiserum and general anti
      profilin antisera demonstrated that PRF1 protein levels also were one-half those
      found in wild-type seedlings, although total profilin levels were unaffected.
      Mutant seedlings no longer could downregulate PRF1 levels in the light, as did
      wild type. Consistent with their molecular phenotypes, young mutant seedlings
      displayed several morphological phenotypes but developed into apparently normal
      adult plants. Their initial germination rate and development were slow, and they
      produced excessive numbers of root hairs. Mutant seedlings had abnormally raised
      cotyledons, elongated hypocotyls, and elongated cells in the hypocotyl, typical
      of phenotypes associated with some defects in light and circadian responses. A
      wild-type PRF1 transgene fully complements the hypocotyl phenotypes in the prf1-1
      mutant. The ability of profilin to regulate actin polymerization and participate
      directly in signal transduction pathways is discussed in light of the prf1-1
      phenotypes.

PMID- 11340192
TI  - Hyperosmotic stress induces the rapid phosphorylation of a soybean
      phosphatidylinositol transfer protein homolog through activation of the protein
      kinases SPK1 and SPK2.
AB  - Although phosphatidylinositol transfer proteins (PITPs) are known to serve
      critical functions in regulating a varied array of signal transduction processes
      in animals and yeast, the discovery of a similar class of proteins in plants
      occurred only recently. Here, we report the participation of Ssh1p, a soybean
      PITP-like protein, in the early events of osmosensory signal transduction in
      plants, a function not attributed previously to animal or yeast PITPs. Exposure
      of plant tissues to hyperosmotic stress led to the rapid phosphorylation of
      Ssh1p, a modification that decreased its ability to associate with membranes. An
      osmotic stress-activated Ssh1p kinase activity was detected in several plant
      species by presenting recombinant Ssh1p as a substrate in in-gel kinase assays.
      Elements of a similar osmosensory signaling pathway also were conserved in yeast,
      an observation that facilitated the identification of soybean protein kinases
      SPK1 and SPK2 as stress-activated Ssh1p kinases. This study reveals the
      activation of SPK1 and/or SPK2 and the subsequent phosphorylation of Ssh1p as two
      early successive events in a hyperosmotic stress-induced signaling cascade in
      plants. Furthermore, Ssh1p is shown to enhance the activities of a plant
      phosphatidylinositol 3-kinase and phosphatidylinositol 4-kinase, an observation
      that suggests that the ultimate function of Ssh1p in cellular signaling is to
      alter the plant's capacity to synthesize phosphoinositides during periods of
      hyperosmotic stress.

PMID- 11340193
TI  - Reversible calcium-regulated stopcocks in legume sieve tubes.
AB  - Sieve tubes of legumes (Fabaceae) contain characteristic P-protein crystalloids
      with controversial function. We studied their behavior by conventional light,
      electron, and confocal laser scanning microscopy. In situ, crystalloids are able
      to undergo rapid (<1 sec) and reversible conversions from the condensed resting
      state into a dispersed state, in which they occlude the sieve tubes. Crystalloid
      dispersal is triggered by plasma membrane leakage induced by mechanical injury or
      permeabilizing substances. Similarly, abrupt turgor changes imposed by osmotic
      shock cause crystalloid dispersal. Because chelators generally prevent the
      response, divalent cations appear to be the decisive factor in crystalloid
      expansion. Cycling between dispersal and condensation can be induced in opened
      cells by repetitive exchange of bathing media containing either Ca(2)+ or
      chelators. Sr(2)+ and Ba(2)+, but not Mg(2)+, are equally active. In conclusion,
      the fabacean P-protein crystalloids represent a novel class of mechanically
      active proteinaceous structures, which provide an efficient mechanism with which
      to control sieve tube conductivity.

PMID- 11340194
TI  - The maize golden2 gene defines a novel class of transcriptional regulators in
      plants.
AB  - In the C4 plant maize, three photosynthetic cell types differentiate: C4 bundle
      sheath, C4 mesophyll, and C3 mesophyll cells. C3 mesophyll cells represent the
      ground state, whereas C4 bundle sheath and C4 mesophyll cells are specialized
      cells that differentiate in response to light-induced positional signals. The
      Golden2 (G2) gene regulates plastid biogenesis in all photosynthetic cells during
      the C3 stages of development. However, G2 function is specifically committed to
      the differentiation of bundle sheath cell chloroplasts in C4 leaf blades. In this
      article, we report the isolation of G2-like (Glk) genes from maize and rice,
      providing evidence for a family of Glk genes in plants. The expression profiles
      of the rice Glk genes suggest that these genes may act redundantly to promote
      photosynthetic development in this C3 species. In maize, G2 and ZmGlk1
      transcripts accumulate primarily in C4 bundle sheath and C4 mesophyll cells,
      respectively, suggesting a specific role for each gene in C4 differentiation. We
      show that G2 and ZmGLK1 both can transactivate reporter gene transcription and
      dimerize in yeast, which supports the idea that these proteins act as
      transcriptional regulators of cell-type differentiation processes.

PMID- 11340195
TI  - Bacterial genomic reorganization upon DNA replication.

PMID- 11340197
TI  - Feynman's path-integral approach for intense-laser-atom interactions.
AB  - Atoms interacting with intense laser fields can emit electrons and photons of
      very high energies. An intuitive and quantitative explanation of these highly
      nonlinear processes can be found in terms of a generalization of classical
      Newtonian particle trajectories, the so-called quantum orbits. Very few quantum
      orbits are necessary to reproduce the experimental results. These orbits are
      clearly identified, thus opening the way for an efficient control as well as
      previously unknown applications of these processes.

PMID- 11340196
TI  - Recognition of cognate transfer RNA by the 30S ribosomal subunit.
AB  - Crystal structures of the 30S ribosomal subunit in complex with messenger RNA and
      cognate transfer RNA in the A site, both in the presence and absence of the
      antibiotic paromomycin, have been solved at between 3.1 and 3.3 angstroms
      resolution. Cognate transfer RNA (tRNA) binding induces global domain movements
      of the 30S subunit and changes in the conformation of the universally conserved
      and essential bases A1492, A1493, and G530 of 16S RNA. These bases interact
      intimately with the minor groove of the first two base pairs between the codon
      and anticodon, thus sensing Watson-Crick base-pairing geometry and discriminating
      against near-cognate tRNA. The third, or "wobble," position of the codon is free
      to accommodate certain noncanonical base pairs. By partially inducing these
      structural changes, paromomycin facilitates binding of near-cognate tRNAs.

PMID- 11340198
TI  - Density fluctuations under confinement: when is a fluid not a fluid?
AB  - Knowing the behavior of a fluid in small volumes is essential for the
      understanding of a vast array of common problems in science, such as biological
      interactions, fracture propagation, and molecular tribology and adhesion, as well
      as pressure solvation and other geophysical processes. When a fluid is confined,
      its phase behavior is altered and excluded-volume effects become apparent.
      Pioneering measurements performed with the surface forces apparatus have revealed
      so-called structural or oscillatory solvation forces as well as the occurrence of
      a finite shear stress, which was interpreted as a solidification transition.
      Here, we report measurements obtained with an extended surface forces apparatus,
      which makes use of fast spectral correlation to gain insight into the behavior of
      a thin film of cyclohexane confined within attoliter volumes, with simultaneous
      measurement of film thickness and refractive index. With decreasing pore width,
      cyclohexane is found to undergo a drastic transition from a three-dimensional
      bulk fluid to a two-dimensional adsorbate with strikingly different properties.
      Long-range density fluctuations of unexpected magnitude are observed.

PMID- 11340199
TI  - Water at hydrophobic surfaces: weak hydrogen bonding and strong orientation
      effects.
AB  - Vibrational studies that selectively probe molecular structure at CCl4/H2O and
      hydrocarbon/H2O interfaces show that the hydrogen bonding between adjacent water
      molecules at these interfaces is weak, in contrast to generally accepted models
      of water next to fluid hydrophobic surfaces that suggest strong hydrogen bonding.
      However, interactions between these water molecules and the organic phase result
      in substantial orientation of these weakly hydrogen-bonded water molecules in the
      interfacial region. The results have important implications for understanding
      water adjacent to hydrophobic surfaces and the penetration of water into
      hydrophobic phases.

PMID- 11340200
TI  - Controlled rotation of optically trapped microscopic particles.
AB  - We demonstrate controlled rotation of optically trapped objects in a spiral
      interference pattern. This pattern is generated by interfering an annular shaped
      laser beam with a reference beam. Objects are trapped in the spiral arms of the
      pattern. Changing the optical path length causes this pattern, and thus the
      trapped objects, to rotate. Structures of silica microspheres, microscopic glass
      rods, and chromosomes are set into rotation at rates in excess of 5 hertz. This
      technique does not depend on intrinsic properties of the trapped particle and
      thus offers important applications in optical and biological micromachines.

PMID- 11340201
TI  - Phonon density of states of iron up to 153 gigapascals.
AB  - We report phonon densities of states (DOS) of iron measured by nuclear resonant
      inelastic x-ray scattering to 153 gigapascals and calculated from ab initio
      theory. Qualitatively, they are in agreement, but the theory predicts density at
      higher energies. From the DOS, we derive elastic and thermodynamic parameters of
      iron, including shear modulus, compressional and shear velocities, heat capacity,
      entropy, kinetic energy, zero-point energy, and Debye temperature. In comparison
      to the compressional and shear velocities from the preliminary reference Earth
      model (PREM) seismic model, our results suggest that Earth's inner core has a
      mean atomic number equal to or higher than pure iron, which is consistent with an
      iron-nickel alloy.

PMID- 11340202
TI  - Production of refractory dissolved organic matter by bacteria.
AB  - Most of the oceanic reservoir of dissolved organic matter (DOM) is of marine
      origin and is resistant to microbial oxidation, but little is known about the
      mechanisms of its formation. In a laboratory study, natural assemblages of marine
      bacteria rapidly (in <48 hours) utilized labile compounds (glucose, glutamate)
      and produced refractory DOM that persisted for more than a year. Only 10 to 15%
      of the bacterially derived DOM was identified as hydrolyzable amino acids and
      sugars, a feature consistent with marine DOM. These results suggest that
      microbial processes alter the molecular structure of DOM, making it resistant to
      further degradation and thereby preserving fixed carbon in the ocean.

PMID- 11340203
TI  - Requirement of phospholipase Cdelta4 for the zona pellucida-induced acrosome
      reaction.
AB  - Several phospholipase C (PLC) isoforms have been found in male and female
      mammalian gametes, and splicing isoforms of PLCdelta4 are predominantly expressed
      in testis. Here we report that male mice in which the PLCdelta4 gene had been
      disrupted either produced few small litters or were sterile. In vitro
      fertilization studies showed that insemination with PLCdelta4-/- sperm resulted
      in significantly fewer eggs becoming activated and that the calcium transients
      associated with fertilization were absent or delayed. PLCdelta4-/- sperm were
      unable to initiate the acrosome reaction, an exocytotic event required for
      fertilization and induced by interaction with the egg coat, the zona pellucida.
      These data demonstrate that PLCdelta4 functions in the acrosome reaction that is
      induced by the zona pellucida during mammalian fertilization.

PMID- 11340204
TI  - Control of glutamate clearance and synaptic efficacy by glial coverage of
      neurons.
AB  - Analysis of excitatory synaptic transmission in the rat hypothalamic supraoptic
      nucleus revealed that glutamate clearance and, as a consequence, glutamate
      concentration and diffusion in the extracellular space, is associated with the
      degree of astrocytic coverage of its neurons. Reduction in glutamate clearance,
      whether induced pharmacologically or associated with a relative decrease of glial
      coverage in the vicinity of synapses, affected transmitter release through
      modulation of presynaptic metabotropic glutamate receptors. Astrocytic wrapping
      of neurons, therefore, contributes to the regulation of synaptic efficacy in the
      central nervous system.

PMID- 11340205
TI  - Glia-synapse interaction through Ca2+-permeable AMPA receptors in Bergmann glia.
AB  - Glial cells express a variety of neurotransmitter receptors. Notably, Bergmann
      glial cells in the cerebellum have Ca2+-permeable alpha-amino-3-hydroxy-5-methyl
      4-isoxazolepropionic acid (AMPA)-type glutamate receptors (AMPARs) assembled
      without the GluR2 subunit. To elucidate the role of these Ca2+-permeable AMPARs,
      we converted them into Ca2+-impermeable receptors by adenoviral-mediated delivery
      of the GluR2 gene. This conversion retracted the glial processes ensheathing
      synapses on Purkinje cell dendritic spines and retarded the removal of
      synaptically released glutamate. Furthermore, it caused multiple innervation of
      Purkinje cells by the climbing fibers. Thus, the glial Ca2+-permeable AMPARs are
      indispensable for proper structural and functional relations between Bergmann
      glia and glutamatergic synapses.

PMID- 11340206
TI  - Integrated genomic and proteomic analyses of a systematically perturbed metabolic
      network.
AB  - We demonstrate an integrated approach to build, test, and refine a model of a
      cellular pathway, in which perturbations to critical pathway components are
      analyzed using DNA microarrays, quantitative proteomics, and databases of known
      physical interactions. Using this approach, we identify 997 messenger RNAs
      responding to 20 systematic perturbations of the yeast galactose-utilization
      pathway, provide evidence that approximately 15 of 289 detected proteins are
      regulated posttranscriptionally, and identify explicit physical interactions
      governing the cellular response to each perturbation. We refine the model through
      further iterations of perturbation and global measurements, suggesting hypotheses
      about the regulation of galactose utilization and physical interactions between
      this and a variety of other metabolic pathways.

PMID- 11340207
TI  - Vital involvement of a natural killer cell activation receptor in resistance to
      viral infection.
AB  - Natural killer (NK) cells are lymphocytes that can be distinguished from T and B
      cells through their involvement in innate immunity and their lack of rearranged
      antigen receptors. Although NK cells and their receptors were initially
      characterized in terms of tumor killing in vitro, we have determined that the NK
      cell activation receptor, Ly-49H, is critically involved in resistance to murine
      cytomegalovirus in vivo. Ly-49H requires an immunoreceptor tyrosine-based
      activation motif (ITAM)-containing transmembrane molecule for expression and
      signal transduction. Thus, NK cells use receptors functionally resembling ITAM
      coupled T and B cell antigen receptors to provide vital innate host defense.

PMID- 11340208
TI  - Stroke: 30 years of progress: 1982-1987.

PMID- 11340209
TI  - Chiropractic manipulation and stroke: a population-based case-control study.
AB  - BACKGROUND AND PURPOSE: Several reports have linked chiropractic manipulation of
      the neck to dissection or occlusion of the vertebral artery. However, previous
      studies linking such strokes to neck manipulation consist primarily of
      uncontrolled case series. We designed a population-based nested case-control
      study to test the association. METHODS: Hospitalization records were used to
      identify vertebrobasilar accidents (VBAs) in Ontario, Canada, during 1993-1998.
      Each of 582 cases was age and sex matched to 4 controls from the Ontario
      population with no history of stroke at the event date. Public health insurance
      billing records were used to document use of chiropractic services before the
      event date. RESULTS: Results for those aged <45 years showed VBA cases to be 5
      times more likely than controls to have visited a chiropractor within 1 week of
      the VBA (95% CI from bootstrapping, 1.32 to 43.87). Additionally, in the younger
      age group, cases were 5 times as likely to have had >/=3 visits with a cervical
      diagnosis in the month before the case's VBA date (95% CI from bootstrapping,
      1.34 to 18.57). No significant associations were found for those aged >/=45
      years. CONCLUSIONS: While our analysis is consistent with a positive association
      in young adults, potential sources of bias are also discussed. The rarity of VBAs
      makes this association difficult to study despite high volumes of chiropractic
      treatment. Because of the popularity of spinal manipulation, high-quality
      research on both its risks and benefits is recommended.

PMID- 11340210
TI  - Utilization of intravenous tissue-type plasminogen activator for ischemic stroke
      at academic medical centers: the influence of ethnicity.
AB  - BACKGROUND AND PURPOSE: We sought to measure the overall rate of usage of tissue
      type plasminogen activator (tPA) for ischemic stroke at academic medical centers,
      and to determine whether ethnicity was associated with usage. METHODS: Between
      June and December 1999, 42 academic medical centers in the United States each
      identified 30 consecutive ischemic stroke cases. Medical records were reviewed
      and information on demographics, medical history, and treatment were abstracted.
      Rates of tPA use were compared for African Americans and whites in univariate
      analysis and after adjustment for age, gender, stroke severity, and type of
      medical insurance with multivariable logistic regression. RESULTS: Complete
      information was available for 1195 ischemic stroke patients; 788 were whites and
      285 were African Americans: Overall, 49 patients (4.1%) received tPA. In the
      subgroup of 189 patients without a documented contraindication to therapy, 39
      (20.6%) received tPA. Ten (20%) of those receiving tPA had documented
      contraindication. African Americans were one fifth as likely to receive tPA as
      whites (1.1% African Americans versus 5.3%; P=0.001), and the difference
      persisted after adjustment (OR 0.21, 95% CI 0.06 to 0.68; P=0.01). When
      comparison was restricted to those without a documented contraindication to tPA,
      the difference remained significant (OR 0.24, 95% CI 0.06 to 0.93; P=0.04).
      Medical insurance type was independently associated with tPA treatment. After
      adjustment for ethnicity and other demographic characteristics, those with
      Medicaid or no insurance were one ninth as likely to receive tPA as those with
      private medical insurance (OR 0.11, 95% CI 0.02 to 0.17; P=0.003). CONCLUSIONS:
      tPA is used infrequently for ischemic stroke at US academic medical centers, even
      among qualifying candidates. African Americans are significantly less likely to
      receive tPA for ischemic stroke. Contraindications to treatment do not appear to
      account for the difference.

PMID- 11340211
TI  - Insulin resistance and elevated levels of tissue plasminogen activator in first
      degree relatives of South Asian patients with ischemic cerebrovascular disease.
AB  - BACKGROUND AND PURPOSE: South Asians in the United Kingdom suffer from an
      increased mortality from cerebrovascular disease compared with whites. Evidence
      suggests that the relatives of white stroke patients are at increased risk of
      vascular disease. The aim of this study was to investigate atherothrombotic risk
      factors in the first-degree relatives of South Asian patients suffering from
      ischemic cerebrovascular disease and to compare them with South Asian subjects
      free from clinically detectable cerebrovascular disease. METHODS: We compared 143
      relatives of South Asians with ischemic stroke (South Asian relatives group) with
      146 South Asian control subjects from West Yorkshire, UK. RESULTS: The ages and
      ethnic and sex distributions of South Asian relatives and South Asian controls
      were similar. There were no significant differences in body mass index, waist-hip
      ratio, number of current smokers, and past medical history of hypertension,
      diabetes mellitus, or myocardial infarction between the 2 groups. Fasting blood
      glucose, glycosylated hemoglobin (HbA(1c)), total cholesterol, triglycerides, and
      HDL cholesterol were similar in the 2 groups. Fasting insulin (South Asian
      relatives, 12.0; South Asian controls, 8.5 mU/L; P<0.0001) (independent of tissue
      plasminogen activator) and insulin resistance (derived by Homeostasis Model
      Assessment) (South Asian relatives, 2.7; South Asian controls, 1.9; P=0.001) were
      significantly raised in stroke relatives. Stroke relatives showed elevated levels
      of tissue plasminogen activator (South Asian relatives, 11.6; South Asian
      controls, 8.4 ng/mL; P<0.0001), which was independent of plasma insulin. There
      were no differences in plasminogen activator inhibitor antigen or activity
      between the groups. CONCLUSIONS: South Asians stroke relatives exhibit
      hyperinsulinemia, increased insulin resistance, and increased tissue plasminogen
      activator levels. These observations might account for increased susceptibility
      to atherothrombotic disease in this ethnic group.

PMID- 11340212
TI  - Intravenous tPA for ischemic stroke team performance over time, safety, and
      efficacy in a single-center, 2-year experience.
AB  - BACKGROUND AND PURPOSE: Safety and efficacy concerns toward thrombolysis for
      ischemic stroke prevail among many neurologists because of the risks of
      hemorrhage and the small proportion of suitable patients. We therefore
      prospectively assessed feasibility, safety, efficacy, and team performance in a
      single center to prove whether thrombolytic treatment is practical in daily
      clinical routine. METHODS: Patients were prospectively recruited over a 2-year
      period. Major inclusion and exclusion criteria from large, randomized controlled
      trials were combined. Prespecified outcome parameters were the modified Rankin
      scale (MRS) and the Barthel Index (BI) at 3 months and symptomatic hemorrhagic
      complications. In addition, certain time intervals during the diagnostic process
      preceding thrombolysis were prospectively recorded. RESULTS: Within 2 years a
      total of 75 patients underwent intravenous thrombolysis, corresponding to 9.4% of
      all admitted patients with stroke and 14.9% of patients with ischemic stroke.
      Mean+/-SD age was 68+/-13 (range 34 to 90) years; median baseline National
      Institutes of Health Stroke Scale score was 13+/-6 (range 2 to 34). Thrombolysis
      was started at an average time of 144 minutes after symptom onset, and 13
      patients (17.3%) were treated beyond 3 hours. Two cerebral hemorrhages (2.7%)
      occurred. Outcome according to the MRS was good (MRS 0 to 1) in 40%, moderate
      (MRS 2 to 3) in 32%, and poor (MRS 4 to 5) in 13%; the corresponding results, as
      measured by the BI, were 61% (BI 95 to 100, good), 16% (BI 55 to 90, moderate),
      and 8% (BI 0 to 50, poor). The mortality rate was 15%. Over 2 years the median
      door-to-CT time decreased from 30 to 22 minutes (27%), and the door-to-needle
      time was shortened from 96 to 73 minutes (14%). The mean number of patients
      treated per month increased from 2 to 4. CONCLUSIONS: Thrombolytic therapy can be
      performed safely and efficaciously in daily clinical routine. More than a
      minority of acute stroke patients might be eligible for intravenous thrombolysis.
      The performance of a stroke team can be improved over time, subsequently
      increasing the proportion of eligible patients and thereby the efficiency of the
      method.

PMID- 11340213
TI  - Timing of spontaneous recanalization and risk of hemorrhagic transformation in
      acute cardioembolic stroke.
AB  - BACKGROUND AND PURPOSE: The relationship between reperfusion and hemorrhagic
      transformation (HT) remains uncertain. Therefore, we aimed to clarify the
      relationship between the time course of recanalization and the risk of HT in
      patients with cardioembolic stroke studied within 6 hours of symptom onset.
      METHODS: Fifty-three patients with atrial fibrillation and nonlacunar stroke in
      the middle cerebral artery (MCA) territory admitted within the first 6 hours
      after symptom onset were prospectively studied. Serial TCD examinations were
      performed on admission and at 6, 12, 24, and 48 hours. CT was performed within 6
      hours after stroke onset and again at 36 to 48 hours. RESULTS: Proximal and
      distal MCA occlusions were detected in 32 patients (60.4%) and 18 patients (34%),
      respectively. Early spontaneous recanalization occurring within 6 hours was
      identified in 10 patients (18.8%). Delayed recanalization (>6 hours) occurred in
      28 patients (52.8%). HT on CT scan was detected in 17 patients (32%) within the
      first 48 hours. Only large parenchymal hemorrhage (PH2) was significantly
      associated with an increase (P=0.038, Kruskal-Wallis test) in the National
      Institutes of Health Stroke Scale (NIHSS) score compared with the other subtypes
      of HT. Univariate analysis revealed that an NIHSS score of >14 on baseline
      (P=0.001), proximal MCA occlusion (P=0.004), hypodensity >33% of the MCA
      territory (P=0.012), and delayed recanalization occurring >6 hours of stroke
      onset (P=0.003) were significantly associated with HT. With a multiple logistic
      regression model, delayed recanalization (OR 8.9; 95% CI 2.1 to 33.3) emerged as
      independent predictor of HT. CONCLUSIONS: Delayed recanalization occurring >6
      hours after acute cardioembolic stroke is an independent predictor of HT.

PMID- 11340214
TI  - Diagnosis and initial management of stroke and transient ischemic attack across
      UK health regions from 1992 to 1996: experience of a national primary care
      database.
AB  - BACKGROUND AND PURPOSE: The aim of this study was to establish the difference in
      burden of cerebrovascular disease across the different health regions of the
      United Kingdom and to determine whether the initial management of new cases of
      stroke and transient ischemic attack (TIA) was uniform across the United Kingdom:
      METHODS: The General Practice Research Database (GPRD) is a national database
      used for epidemiological studies. This was a cohort study identifying incident
      cases of stroke and TIA over a 5-year study period between 1992 and 1996. The
      population studied was patients registered with general practitioners
      contributing to the GPRD across the different health regions of the United
      Kingdom: Outcome measures were new diagnoses of stroke and TIA, new prescriptions
      for antiplatelet and anticoagulant agents, and referrals made for specialist
      opinion. RESULTS: The age-adjusted annual incidence rate across all regions was
      151 per 100 000 for stroke and 190 per 100 000 for TIA. There was almost a 2-fold
      difference in the incidence of cerebrovascular disease between the regions. The
      management of stroke and TIA in terms of antiplatelet prescription and of
      referral onward for further opinion to hospital specialists varied significantly
      between regions. CONCLUSIONS: Reported stroke and TIA incidence on the GPRD was
      comparable to that of other European studies. There were striking regional
      differences in the incidence of disease. The primary care management, both in
      prescription and referral rates, varied significantly between the different
      regions. There was a marked underuse of antiplatelet and anticoagulant agents,
      and referral rates for specialists' opinions were low.

PMID- 11340215
TI  - Improving the reliability of stroke subgroup classification using the Trial of
      ORG 10172 in Acute Stroke Treatment (TOAST) criteria.
AB  - BACKGROUND AND PURPOSE: We sought to improve the reliability of the Trial of ORG
      10172 in Acute Stroke Treatment (TOAST) classification of stroke subtype for
      retrospective use in clinical, health services, and quality of care outcome
      studies. The TOAST investigators devised a series of 11 definitions to classify
      patients with ischemic stroke into 5 major etiologic/pathophysiological
      groupings. Interrater agreement was reported to be substantial in a series of
      patients who were independently assessed by pairs of physicians. However, the
      investigators cautioned that disagreements in subtype assignment remain despite
      the use of these explicit criteria and that trials should include measures to
      ensure the most uniform diagnosis possible. METHODS: In preparation for a study
      of outcomes and management practices for patients with ischemic stroke within
      Department of Veterans Affairs hospitals, 2 neurologists and 2 internists first
      retrospectively classified a series of 14 randomly selected stroke patients on
      the basis of the TOAST definitions to provide a baseline assessment of interrater
      agreement. A 2-phase process was then used to improve the reliability of subtype
      assignment. In the first phase, a computerized algorithm was developed to assign
      the TOAST diagnostic category. The reliability of the computerized algorithm was
      tested with a series of synthetic cases designed to provide data fitting each of
      the 11 definitions. In the second phase, critical disagreements in the data
      abstraction process were identified and remaining variability was reduced by the
      development of standardized procedures for retrieving relevant information from
      the medical record. RESULTS: The 4 physicians agreed in subtype diagnosis for
      only 2 of the 14 baseline cases (14%) using all 11 TOAST definitions and for 4 of
      the 14 cases (29%) when the classifications were collapsed into the 5 major
      etiologic/pathophysiological groupings (kappa=0.42; 95% CI, 0.32 to 0.53). There
      was 100% agreement between classifications generated by the computerized
      algorithm and the intended diagnostic groups for the 11 synthetic cases. The
      algorithm was then applied to the original 14 cases, and the diagnostic
      categorization was compared with each of the 4 physicians' baseline assignments.
      For the 5 collapsed subtypes, the algorithm-based and physician-assigned
      diagnoses disagreed for 29% to 50% of the cases, reflecting variation in the
      abstracted data and/or its interpretation. The use of an operations manual
      designed to guide data abstraction improved the reliability subtype assignment
      (kappa=0.54; 95% CI, 0.26 to 0.82). Critical disagreements in the abstracted data
      were identified, and the manual was revised accordingly. Reliability with the use
      of the 5 collapsed groupings then improved for both interrater (kappa=0.68; 95%
      CI, 0.44 to 0.91) and intrarater (kappa=0.74; 95% CI, 0.61 to 0.87) agreement.
      Examining each remaining disagreement revealed that half were due to ambiguities
      in the medical record and half were related to otherwise unexplained errors in
      data abstraction. CONCLUSIONS: Ischemic stroke subtype based on published TOAST
      classification criteria can be reliably assigned with the use of a computerized
      algorithm with data obtained through standardized medical record abstraction
      procedures. Some variability in stroke subtype classification will remain because
      of inconsistencies in the medical record and errors in data abstraction. This
      residual variability can be addressed by having 2 raters classify each case and
      then identifying and resolving the reason(s) for the disagreement.

PMID- 11340216
TI  - Geographic distribution of stroke incidence within an urban population: relations
      to socioeconomic circumstances and prevalence of cardiovascular risk factors.
AB  - BACKGROUND AND PURPOSE: Geographic differences in stroke incidence indicate a
      potential for prevention. The present study from the city of Malmo, Sweden,
      sought to investigate whether incidence of stroke in residential areas is related
      to prevalence of cardiovascular risk factors and socioeconomic circumstances.
      METHODS: The Stroke Register in Malmo, Sweden, was used for retrieval of the 3540
      patients who suffered a first stroke between 1989 and 1998. The Malmo Diet and
      Cancer cohort (n=28 466) was used to assess area specific prevalence of
      hypertension, diabetes, smoking, and being overweight and for computation of a
      cardiovascular risk score. Socioeconomic circumstances for the 17 administrative
      areas were expressed in terms of a composite score. RESULTS: Standardized stroke
      incidence ranged among areas from 437 to 743 per 100 000 for men and from 223 to
      518 per 100 000 for women. Socioeconomic score correlated significantly with area
      specific stroke rates among men (r=-0.62, P=0.008) and women (r=-0.67, P=0.004).
      Incidence of stroke was significantly associated with cardiovascular risk score
      for each area (men, r=0.53, P<0.05; women, r=0.76, P<0.001). The cardiovascular
      score and the socioeconomic score together accounted for 44% of the geographic
      variance among men and 63% among women. CONCLUSIONS: Marked differences occurred
      in stroke incidence among residential areas within this urban population. High
      rate areas were characterized by a higher prevalence of smoking, hypertension,
      diabetes, and being overweight and by inferior socioeconomic circumstances. These
      risk factors accounted for a substantial proportion of the geographic variance in
      incidence of stroke.

PMID- 11340217
TI  - Changes in cardiovascular risk factors during the perimenopause and postmenopause
      and carotid artery atherosclerosis in healthy women.
AB  - BACKGROUND AND PURPOSE: The objectives of this study were to describe the changes
      in cardiovascular risk factors during the perimenopausal and early postmenopausal
      years and correlate those changes in risk factors with carotid intimal-medial
      thickness (IMT) and plaque index measured 5 to 8 years after menopause. METHODS:
      Participants were women (n=372) from Allegheny County, Pennsylvania, enrolled in
      the Healthy Women Study who had been postmenopausal for at least 5 years. Risk
      factor changes were measured during the perimenopause, ie, between the
      premenopausal and first year postmenopausal examinations, and during the early
      postmenopause, ie, between the first and fifth year postmenopausal examinations.
      Carotid ultrasound scans measured IMT and plaque at examinations 5 to 8 years
      after menopause among 314 of the women. RESULTS: Increases in LDL cholesterol and
      triglycerides and declines in HDL cholesterol were greater during perimenopause
      than postmenopause, whereas increases in blood pressure and fasting glucose
      levels were greater during postmenopause. Premenopausal systolic and pulse
      pressure, LDL and HDL cholesterol, triglycerides, and body mass index predicted
      IMT and plaque. Only the change in pulse pressure between premenopausal and first
      year postmenopausal examinations was related to both IMT and plaque. CONCLUSIONS:
      Absolute risk for cardiovascular disease increases substantially in midlife, with
      a particularly adverse effect on lipid metabolism at the menopause. Premenopausal
      levels of risk factors are adequate to identify which women should be targeted
      for intervention.

PMID- 11340218
TI  - Does pretreatment with statins improve clinical outcome after stroke? A pilot
      case-referent study.
AB  - BACKGROUND AND PURPOSE: In primary and secondary prevention trials, statins have
      been shown to reduce the risk of stroke. In addition to lipid lowering, statins
      have a number of antiatherothrombotic and neuroprotective properties. In a
      preliminary observational study, we explored whether clinical outcome is improved
      in patients who are on treatment with statins when stroke occurs. METHODS: We
      conducted a population-based case-referent study of 25- to 74-year-old stroke
      patients with, for each case of a patient who was on statin treatment at the
      onset of stroke (n=125), 2 referent patients who were not treated with statins
      but were matched for age, gender, year of onset, and stroke subtype (n=250).
      RESULTS: The unadjusted odds ratio for early discharge to home (versus late
      discharge or death) was 1.41 (95% CI 0.91 to 2.17) when patients on statin
      treatment were compared with referent stroke patients not on statins. Prognostic
      factors were, in general, more unfavorable among patients on statins. When this
      was adjusted for in a logistic regression model, the use of statins was a
      moderately strong but statistically nonsignificant predictor of discharge to home
      (multiple-adjusted odds ratio 1.42, 95% CI 0.90 to 2.22). CONCLUSIONS: The
      statistical power of this case-referent study was such that only large beneficial
      effects of statins in acute stroke could be confirmed. However, the observed
      trend, together with experimental observations, is interesting enough to warrant
      a more detailed analysis of the relationship between statins and stroke outcome.

PMID- 11340219
TI  - Elevated plasma homocysteine levels and risk of silent brain infarction in
      elderly people.
AB  - BACKGROUND AND PURPOSE: Silent brain infarction (SBI) on MRI is common in elderly
      people, and recent studies have demonstrated that SBI increases the risk of
      progression to clinically apparent stroke and cognitive decline. Therefore, an
      early and accurate detection of SBI and a search for potential treatable risk
      factors may have a significant impact on public health. METHODS: Community
      dwelling elderly people aged >/=66 years who participated in the present study
      (n=153) underwent brain MRI and standardized physical and neuropsychological
      examinations as well as blood biochemistry determinations, including total plasma
      homocysteine (pHcy), renal function, vitamin status, and polymorphisms of the
      methylenetetrahydrofolate reductase gene. RESULTS: SBI was found in 24.8% of the
      participants. In the univariate analysis, the pHcy levels in subjects with SBI
      (13.6+/-4.1 micromol/L) were significantly higher (P=0.0004) than those in
      subjects without SBI (11.0+/-3.3 micromol/L). When pHcy levels were stratified
      into high (>/=15.1 mmol/L), moderate (11.6 to 15.0 mmol/L), and low (</=11.5
      mmol/L) groups, age (P<0.0001), male sex (P<0.0001), the habits of cigarette
      smoking (P<0.0001) and of alcohol consumption (P=0.0002), and folate levels
      (P=0.01) were significantly associated with an elevation of pHcy levels. The
      elevated pHcy levels were significantly associated with SBI after individual
      adjustment for age, sex, hypertension, renal function, and the habits of smoking
      and alcohol consumption. CONCLUSIONS: pHcy level is associated with age and
      nutritional and other lifestyle factors, and it contributes to a risk for SBI.

PMID- 11340220
TI  - Acoustic shadowing on B-mode ultrasound of the carotid artery predicts ischemic
      stroke: the Atherosclerosis Risk in Communities (ARIC) study.
AB  - BACKGROUND AND PURPOSE: We examined the relationship of carotid artery lesions
      (CALs), with and without acoustic shadowing (AS), to incident ischemic stroke
      events in the Atherosclerosis Risk in Communities study cohort. METHODS: The
      study population consisted of 13 123 men and women aged 45 to 64 years, and free
      of stroke, examined during 1986-1989. Over an average follow-up time of 8.0
      years, 226 incident ischemic stroke cases (thromboembolic brain infarctions) were
      identified and classified by a standardized protocol. Three levels of exposure
      were defined on the basis of the presence of B-mode ultrasound-detected CALs and
      AS in a 3-cm segment of the carotid arteries centered at the bifurcation.
      RESULTS: The hazard ratio for ischemic stroke adjusted for age, ethnicity, and
      study site for women with a CAL without AS, compared with those without a CAL,
      was 1.92 (95% CI, 1.23, 3.01), and the hazard ratio comparing those with a CAL
      with AS with those without a CAL was 4.01 (95% CI, 2.28, 7.06). The corresponding
      hazard ratios for men were 1.99 (95% CI, 1.36, 2.91) and 2.23 (95% CI, 1.32,
      3.79). Although adjustment for diabetes, hypertension medication, systolic blood
      pressure, left ventricular hypertrophy score, fibrinogen, von Willebrand factor
      antigen, and smoking status attenuated these associations somewhat, when compared
      with no evidence of CALs, CALs with AS remained statistically significant
      predictors of ischemic stroke in women, while CALs without AS were predictive of
      ischemic stroke in men. CONCLUSIONS: B-mode ultrasound-detected CALs and AS serve
      as markers of atherosclerosis and thus are predictive of ischemic stroke.

PMID- 11340221
TI  - Spontaneous echo contrast caused by platelet and leukocyte aggregates?
AB  - BACKGROUND AND PURPOSE: Spontaneous echocardiographic contrast (SEC) is
      correlated to clinical thromboembolic events. We sought to determine the origin
      of SEC by utilizing direct analysis of left atrial blood. METHODS: We examined
      the blood of 13 patients with and 19 without SEC. Blood samples were taken from
      the femoral vein and artery and from the right and left atria after transseptal
      puncture. Samples were incubated with fluorescence-labeled antibodies directed
      against the platelet (CD41a-PE, CD42b-PE, and CD62p-FITC) and leukocyte membrane
      epitopes (CD45-APC and CD14-FITC). The expressed epitopes were analyzed by dual
      laser flow cytometry immediately after blood withdrawal. RESULTS: In the
      peripheral blood of both groups, more activation and aggregation were found in
      the venous blood than in the arterial blood (CD41a, P=0.007; CD14neutro, P=0.017;
      and leukocyte-platelet aggregates [LTAg], P=0.002). In patients without SEC, the
      degree of activation and aggregation of the cardiac samples closely resembled the
      results of the peripheral samples. The degree of activation and aggregation was
      significantly higher in the right atrium than in the left atrium (LTAg, P<0.01;
      leukocyte activation, P<0.01; CD41a, P<0.01; CD62p, P<0.02). In contrast, in
      patients with SEC the parameters of platelet and leukocyte activation as well as
      LTAg was significantly higher in the left atrium than in the right atrium of the
      same patient (all P<0.01). A correlation between the amount of SEC and platelet
      monocyte aggregates could be found (r=0.92, P<0.0001). CONCLUSIONS: The
      hypothesis that platelet aggregates are involved in the pathogenesis of SEC is
      supported by the fact that platelets in the left atrium of patients with SEC
      showed more activation.

PMID- 11340222
TI  - Functional MRI detects posterior shifts in primary sensorimotor cortex activation
      after stroke: evidence of local adaptive reorganization?
AB  - BACKGROUND AND PURPOSE: Further recovery from stroke can occur late, long after
      the end of the apparent evolution of pathological changes. This observation and
      evidence obtained from functional imaging for altered patterns of activation
      after brain injury suggest that cortical reorganization may contribute to
      recovery. Here, we have tested for potentially adaptive reorganization in the
      primary sensorimotor cortex. METHODS: We used functional MRI to study brain
      activation with dominant hand movement in right-handed healthy control subjects
      (n=20) and in patients after subcortical ischemic infarcts causing mild to
      moderate right hemiparesis (n=8). The numbers of pixels activated above threshold
      and the geometric centers of activation clusters were determined. RESULTS:
      Although random-effects analysis identified some differences in activation
      maxima, similar regions of the brain were activated with sequential finger
      tapping in the patient and control groups. However, consistent with the
      heterogeneity in the locations, sizes, and times after the infarcts, patterns and
      magnitudes of activation showed some heterogeneity between patients. Nonetheless,
      for the group as a whole, there was a decreased motor cortex lateralization index
      (-0.1+/-0.7 in patients and 0.7+/-0.3 in control subjects, P=0.05). The geometric
      center of activation of the primary sensorimotor cortex activation cluster
      contralateral to the affected hand in patients was also shifted posteriorly (mean
      12 mm, P<0.04) relative to that of the control subjects. To confirm the latter
      observation, the activation response with a simple hand-tapping task was examined
      in some of the subjects. With this task, there was also a trend (mean 10 mm,
      P=0.07) toward a more posterior activation in patients. CONCLUSIONS: These
      results confirm altered patterns of activation in the contralateral and
      ipsilateral primary sensorimotor cortices after recovery from strokes causing
      hemiparesis. These (and other changes) suggest that modulation of widely
      distributed parts of the cortical network for motor control may contribute to
      adaptations leading to functional recovery after stroke.

PMID- 11340223
TI  - Viability thresholds of ischemic penumbra of hyperacute stroke defined by
      perfusion-weighted MRI and apparent diffusion coefficient.
AB  - BACKGROUND AND PURPOSE: The penumbra of ischemic stroke consists of hypoperfused,
      but not irreversibly damaged, tissue surrounding the ischemic core. The purpose
      of this study was to determine viability thresholds in the ischemic penumbra,
      defined as the perfusion/diffusion mismatch in hyperacute stroke, by the use of
      diffusion- and perfusion-weighted MRI (DWI and PWI, respectively). METHODS: DWI
      and PWI were performed in 11 patients </=6 hours after the onset of symptoms of
      acute ischemic stroke. Regions of interest (ROIs) were placed covering the
      ischemic core (ROI 1), the penumbra that progressed to infarction on the basis of
      follow-up scans (ROI 2), and the penumbra that recovered (ROI 3). The ratios of
      relative cerebral blood flow (rCBF), relative cerebral blood volume (rCBV), mean
      transit time (MTT), and apparent diffusion coefficient were calculated as lesion
      ROIs relative to the contralateral mirror ROIS: RESULTS: The post hoc analysis
      showed that the penumbra progressed to infarction at the following cutoff values:
      rCBF <0.59 and MTT >1.63. Higher sensitivity and accuracy in predicting outcome
      of the penumbra were obtained from the rCBF maps compared with the rCBV and MTT
      maps. The initial rCBV and apparent diffusion coefficient ratios did not
      differentiate between the part of the penumbra that recovered and the part that
      progressed to infarction. The mean rCBF ratio was optimal in distinguishing the
      parts of the penumbra recovering or progressing to infarction. CONCLUSIONS: The
      thresholds found in this study by combined DWI/PWI might aid in the selection of
      patients suitable for therapeutic intervention within 6 hours. However, these
      hypothesized thresholds need to be prospectively tested at the voxel level on a
      larger patient sample before they can be applied clinically.

PMID- 11340224
TI  - Usefulness of magnetic resonance-derived quantitative measurements of cerebral
      blood flow and volume in prediction of infarct growth in hyperacute stroke.
AB  - BACKGROUND AND PURPOSE: The identification of the tissue at risk for infarction
      remains challenging in stroke patients. In this study, we evaluated the value of
      quantitative cerebral blood flow (CBF) and cerebral blood volume (CBV)
      measurements in the prediction of infarct growth in hyperacute stroke. METHODS:
      Fluid-attenuated inversion recovery (FLAIR), diffusion-weighted (DW), and
      gradient-echo echo-planar perfusion-weighted (PW) sequences were obtained in 66
      patients within 6 hours of stroke onset; ischemia was confirmed on follow-up
      FLAIR images. We delineated the following: (1) the initial infarct on DW images,
      (2) the area of hemodynamic disturbance on mean transit time (MTT) maps, and (3)
      the final infarct on follow-up FLAIR images. MTT, CBF, and CBV were calculated in
      the following areas: area of initial infarct (INF), area of infarct growth (IGR,
      final minus initial infarct), the hemodynamically disturbed area that remained
      viable (OLI, hemodynamic disturbance minus final infarct), and all contralateral
      mirror regions. RESULTS: Compared with mirror regions, the MTT in abnormal areas
      was always prolonged. The respective mean+/-SD CBF and CBV values were as
      follows: for INF, 28+/-16 mL/min per 100 g and 6.9+/-2.7%; for IGR, 36+/-20
      mL/min per 100 g and 8.9+/-3.1%; for OLI, 50+/-17 mL/min per 100 g and 11.2+/-3%;
      and for mirror regions, 64+/-23 mL/min per 100 g and 8.7+/-2.5%. The CBV and CBF
      values were significantly different between all abnormal areas (except for the
      CBF between INF and IGR). In the area of DW/PW mismatch, a combined CBF or CBV
      threshold of 35 or 8.2, respectively, predicted evolution to infarction with a
      sensitivity of 81% and a specificity of 76%. CONCLUSIONS: Quantitative
      measurements of CBF and CBV in hyperacute stroke may help to predict infarct
      growth and to select the subjects who will benefit from thrombolysis.

PMID- 11340225
TI  - Neurological deterioration in acute lacunar infarctions: the role of excitatory
      and inhibitory neurotransmitters.
AB  - BACKGROUND AND PURPOSE: The mechanisms involved in the neurological deterioration
      of acute lacunar strokes are unknown. Although accumulating evidence suggests
      that glutamate release plays a role in the progression of territorial
      infarctions, it remains to be established whether excitotoxicity also
      participates in lacunar stroke progression. We investigated whether excitatory
      and inhibitory amino acid concentrations in blood predict subsequent progressive
      motor deficits in lacunar infarctions. METHODS: We studied 113 consecutive
      patients with lacunar infarct, defined by clinical and computed
      tomography/magnetic resonance imaging criteria, within the first 24 hours after
      stroke onset. Neurological deterioration was defined as a decrease of >/=1 points
      in the motor items of the Canadian Stroke Scale in the first 48 hours after
      admission. Glutamate, glycine, and GABA were determined by high-performance
      liquid chromatography in plasma samples obtained on admission. Predictive values,
      sensitivity, specificity, and accuracy of specific glutamate and GABA
      concentrations and glutamatexglycine/GABA index for progression of lacunar stroke
      were calculated. RESULTS: Twenty-seven patients (23.9%) had neurological
      worsening. Plasma concentrations of glutamate (253+/-70 versus 123+/-73
      micromol/L, mean+/-SD) were higher and those of GABA (140+/-63 versus 411+/-97
      nmol/L) were lower in the progressing group than in the nonprogressing group
      (both P<0.001). Glutamate concentrations >200 micromol/L and GABA levels <240
      nmol/L had a positive predictive value for neurological deterioration of 67% and
      84%, respectively. A excitotoxic index >106 had a positive predictive value of
      85%. CONCLUSIONS: These findings suggest that an imbalance between the glutamate
      and GABA concentrations may play a role in the pathophysiology of progressing
      lacunar infarctions.

PMID- 11340226
TI  - White matter damage is associated with matrix metalloproteinases in vascular
      dementia.
AB  - BACKGROUND AND PURPOSE: Vascular disease causes multi-infarct dementia (MID) or
      Binswanger's disease (BD), the latter of which is a progressive form of vascular
      dementia (VaD) associated pathologically with fibrinoid and hyaline changes in
      brain arterioles with injury to the white matter. Clinically, BD patients have
      long-standing hypertension with disturbances of gait and intellect. Because
      matrix metalloproteinases (MMPs) are important in cerebral infarction, we
      hypothesized that disturbances in the MMPs may be involved in VAD: METHODS: Brain
      tissues from 5 patients with VaD of the BD or multi-infarct type (MID) were
      immunostained with antibodies to glial fibrillary acidic protein (GFAP), a
      microglial/macrophage cell marker (PG-M1), gelatinase A (MMP-2), stromelysin-1
      (MMP-3), and gelatinase B (MMP-9). Control tissues were from 8 elderly patients:
      4 with strokes without dementia and 4 without neurological diseases. RESULTS: PG
      M1+ cells appeared around infarcts in patients with strokes without dementia and
      in patients with VAD: In 2 of the 3 BD patients, PG-M1 cells were prominent near
      damaged arterioles and scattered diffusely in white matter. MMP-2 was seen
      normally in perivascular macrophages and in astrocytic processes near blood
      vessels and was present in patients with strokes in reactive astrocytes. MMP-9
      was rarely seen. MMP-3 was seen in PG-M1+ microglial/macrophage cells around the
      acute infarctions. In BD, MMP-3 persisted in tissue macrophages and disappeared
      in long-standing white matter gliosis. CONCLUSIONS: These observations suggest
      that MMPs may participate in the damage to the white matter associated with VAD:
      Microglia/macrophage-induced damage, which is amenable to treatment, may be a
      factor in the progressive forms of VAD:

PMID- 11340227
TI  - Status epilepticus after stroke.
AB  - BACKGROUND AND PURPOSE: objective of our study was to determine the risk and
      predictive factors of status epilepticus (SE) after stroke. METHODS: From 1988 to
      2000, 1174 patients were admitted to the Department of Neurology at the Karadeniz
      Technical University Farabi Hospital with first-time strokes. Of these, 180
      patients had poststroke first-time seizures (PFSs). We followed these 180 PFS
      patients for an average of 3.7 years or until death to determine the occurrence
      rate of SE. By comparing these data with those of PFS patients without SE, we
      investigated whether there were significant differences. RESULTS: A total of 17
      of the 180 PFS patients (9%) had SE. There was no relationship between the
      occurrence of SE and stroke risk factors, stroke type (ischemic or hemorrhagic
      stroke), stroke topography and cause, cortical involvement, size of lesion,
      seizure type, or electroencephalographic findings. SE occurred more frequently
      among patients with a higher disability rating (Rankin scale >3; odds ratio,
      4.36). Recurrent SE was identified in 5 of 17 patients with SE. In all 5 of these
      patients, the first episode of SE occurred within the first 7 days after stroke
      (early-onset SE). Statistical analysis demonstrated that early-onset SE was
      associated with a higher risk for SE recurrence (P=0.003) and a higher mortality
      rate (P=0.04). CONCLUSIONS: SE was not associated with a higher mortality rate
      but with higher functional disability. We also found that early-onset SE (within
      the first 7 days after stroke) was associated with a higher risk for SE
      recurrence and a higher mortality rate than late-onset SE (after 7 days after
      stroke).

PMID- 11340228
TI  - Attributable risk of common and rare determinants of subarachnoid hemorrhage.
AB  - BACKGROUND AND PURPOSE: Smoking, hypertension, alcohol consumption, autosomal
      dominant polycystic kidney disease (ADPKD), and positive family history for
      subarachnoid hemorrhage (SAH) are well-known risk factors for SAH. For effective
      prevention, knowledge about the contribution of these risk factors to the overall
      occurrence of SAH in the general population is pivotal. We therefore investigated
      the population attributable risks of the risk factors for SAH. METHODS: We
      retrieved the relative risk and prevalence of established risk factors for SAH
      from the literature and calculated the population attributable risks of these
      risk factors. RESULTS: Drinking alcohol 100 to 299 g/wk accounted for 11% of the
      cases of SAH, drinking alcohol >/=300 g/wk accounted for 21%, and smoking
      accounted for 20%. An additional 17% of the cases could be attributed to
      hypertension, 11% to a positive family history for SAH, and 0.3% to ADPKD.
      CONCLUSIONS: Screening and preventive treatment of patients with familial
      preponderance of SAH alone will cause a modest reduction of the incidence of SAH
      in the general population. Further reduction can be achieved by reducing the
      prevalence of the modifiable risk factors alcohol consumption, smoking, and
      hypertension.

PMID- 11340229
TI  - Incidence and significance of early aneurysmal rebleeding before neurosurgical or
      neurological management.
AB  - BACKGROUND AND PURPOSE: Rebleeding is a major cause of death and disability in
      aneurysmal subarachnoid hemorrhage (SAH); however, there has been no report
      focusing on rebleeding before hospitalization in neurosurgical or neurological
      institutions. The aim of this study was to clarify the incidence of
      prehospitalization rebleeding, its impact on the clinical course and prognosis in
      patients with aneurysmal SAH, and the possible factors inducing it. METHODS: In
      273 patients who were admitted to our institution within 24 hours after the
      initial SAH bleeding and whose clinical course before admission could be fully
      evaluated, the patients' clinical conditions and CT findings on admission,
      operability, prognosis, and possible factors inducing rebleeding were
      comparatively evaluated between the patients with and without an episode of
      prehospitalization rebleeding. RESULTS: Of the 273 patients, 37 (13.6%) patients
      suffered from 39 episodes of rebleeding in the ambulance or at the referring
      hospital before admission to our hospital. The peak time of rebleeding was within
      2 hours (77%), in which the incidence was statistically significant compared with
      that occurring 2 to 8 hours after the initial SAH bleeding (P<0.01). The group
      experiencing rebleeding showed more severe Hunt and Hess grades on admission,
      higher rates of intracerebral hematoma, of intraventricular hematoma, and of
      subdural hematoma on CT scan on admission, less operability, and poorer prognoses
      with statistically significant differences compared with the group that did not
      experience rebleeding. Systolic arterial pressure >160 mm Hg was a possible risk
      factor of rebleeding (odds ratio 3.1, 95% CI 1.5 to 6.8). CONCLUSIONS: Rebleeding
      during transfer and at the referring hospital is not rare. To improve overall
      outcome of aneurysmal SAH, the results obtained in this study should be made
      available to general practitioners and the doctors devoted to emergency medicine.

PMID- 11340230
TI  - Association of apolipoprotein E polymorphism with outcome after aneurysmal
      subarachnoid hemorrhage: a preliminary study.
AB  - BACKGROUND AND PURPOSE: Variation in the outcome after aneurysmal subarachnoid
      hemorrhage (SAH) is not fully explained by known prognostic factors. APOE
      genotype is the most important genetic determinant of susceptibility to
      Alzheimer's disease, and it is also shown to be associated with the outcome after
      traumatic brain injury. We studied the association of apolipoprotein E
      polymorphism with the outcome after aneurysmal SAH. METHODS: A total of 160
      consecutive patients were admitted after SAH to a neurosurgical unit. The
      clinical assessment after the SAH was performed with the Hunt and Hess grading
      scale. The severity of the bleeding as visualized on CT was assessed by Fisher's
      grading system. Outcome was assessed with the Glasgow Outcome SCALE: APOE
      genotypes were determined by polymerase chain reaction-restriction fragment
      length polymorphism. RESULTS: 126 patients had aneurysmatic SAH, and detailed
      information on outcome and APOE genotype was available for 108 patients (86%).
      Sixteen (40%) of 40 patients with APOE epsilon4 had an unfavorable outcome
      compared with 13 (19%) of 68 without the APOE epsilon4 allele (OR 2.8, 95% CI
      1.18 to 6.77). Association was more significant after adjustment for age,
      rebleeding, clinical status on admission, and CT scan findings (OR 7.1, 95% CI
      1.9 to 26.3; P=0.0035). CONCLUSIONS: Our findings show a significant genetic
      association of APOE polymorphism with outcome after spontaneous aneurysmal SAH.
      Genetic factors thus seem to explain a part of individual differences in the
      recovery of SAH.

PMID- 11340231
TI  - Temporal relationship between endothelin-1 concentrations and cerebral vasospasm
      in patients with aneurysmal subarachnoid hemorrhage.
AB  - BACKGROUND AND PURPOSE: Endothelin 1 (ET-1) is a potent vasoconstrictor that may
      play a role in cerebral vasospasm following subarachnoid hemorrhage (SAH).
      However, data regarding its pathogenic role in the development of vasospasm are
      controversial. We planned a prospective, observational clinical study to
      investigate the temporal relationship between increased ET-1 production and
      cerebral vasospasm or other neurological sequelae after SAH. METHODS: ET-1 levels
      in cerebrospinal fluid (CSF) were measured in 20 SAH patients from admission
      (within 24 hours from the bleeding) until day 7. Patients received a daily
      transcranial Doppler study and a neurological evaluation. On day 7, angiography
      was performed to verify the degree and extent of vasospasm. Patients were then
      classified as having (1) clinical vasospasm, (2) angiographic vasospasm, (3) no
      vasospasm, or (4) poor neurological condition without significant vasospasm (low
      Glasgow Coma Scale score [GCS]). RESULTS: On admission, ET-1 levels were
      increased in the low-GCS group compared with the other groups (P=0.04). On day 4
      ET-1 levels were not significantly different among groups, whereas on day 7 ET-1
      levels were significantly increased in both the clinical vasospasm and low-GCS
      groups compared with the angiographic vasospasm and no vasospasm groups
      (P<0.005). Moreover, when the low-GCS group was excluded, there was a significant
      relationship between vasospasm grade and CSF ET-1 levels (R(2)=0.73).
      CONCLUSIONS: CSF ET-1 levels were markedly elevated in patients with clinical
      manifestations of vasospasm (day 7) and with a poor neurological condition not
      related to vasospasm. However, ET-1 levels were low in clinical vasospasm
      patients before clinical symptoms were evident (day 4) and remained low in
      angiographic vasospasm patients throughout the study period. Thus, our data
      suggest that CSF ET-1 levels are increased in conditions of severe neuronal
      damage regardless whether this was due to vasospasm or to the primary hemorrhagic
      event. In addition, CSF ET-1 levels paralleled the neurological deterioration but
      were not predictive of vasospasm.

PMID- 11340232
TI  - Risk of aneurysm recurrence in patients with clipped cerebral aneurysms: results
      of long-term follow-up angiography.
AB  - BACKGROUND AND PURPOSE: With many patients living long after microsurgical
      aneurysm clipping for subarachnoid hemorrhage (SAH) and with the evolution of
      intravascular procedures as less invasive alternatives, knowledge of the long
      term results of clipping is becoming important. METHODS: Of 412 patients who
      underwent clipping of ruptured or unruptured cerebral aneurysms at our
      institution between 1976 and 1994 and who survived >3 years after surgery, 225
      patients who were in good general condition and younger than 80 years were
      offered follow-up angiography to detect newly formed aneurysms. Of the 225, 80
      patients (35.6%) agreed to undergo angiography. In addition, 32 patients
      underwent angiography for new medical indications other than SAH. Therefore, 112
      patients underwent angiography, representing a total of 140 clipped aneurysms.
      RESULTS: The mean interval from surgery was 9.3 years for all patients and 9.0
      years for the clipped aneurysms (range 3 to 21 years). Four aneurysm regrowths
      were detected of the 140 (2.9%) clipped aneurysms, representing 3 of 125
      completely clipped aneurysms, 1 of 14 incompletely clipped aneurysms, and 0 of 1
      aneurysm not studied with postoperative angiography. De novo aneurysms were
      detected in 9 of 112 (8.0%) patients. The annual rate of de novo aneurysm
      formation was 0.89%. CONCLUSIONS: This study shows that the annual rate of de
      novo aneurysm formation is relatively high (0.89%) and that the cumulative risk
      becomes significant after 9 years. In consideration of the fatality rate of SAH,
      follow-up angiography may be indicated for patients with clipped aneurysms 9 to
      10 years after surgery.

PMID- 11340233
TI  - Hypertensive caudate hemorrhage prognostic predictor, outcome, and role of
      external ventricular drainage.
AB  - BACKGROUND AND PURPOSE: The purpose of the present study was to analyze the
      outcome and outcome predictors of caudate hemorrhage and role of external
      ventricular drainage in acute hydrocephalus. METHODS: Clinical data from 36
      consecutive patients with hypertensive caudate hemorrhage was used in the present
      study. Age, gender, volume of parenchymal hematoma, hematoma in the internal
      capsule, initial Glasgow Coma Scale (GCS), hydrocephalus, severity of
      intraventricular hemorrhage, and hemorrhagic dilatation of the fourth ventricle
      were analyzed for effect on outcome. Effect of external ventricle drainage for
      hydrocephalus was evaluated by comparing preoperative and postoperative GCS
      scores. RESULTS: By univariate analyses, poor outcome was associated with a poor
      initial GCS score (P=0.016), hydrocephalus (P<0.001), intraventricular hemorrhage
      severity (P<0.01), and hemorrhagic dilatation of the fourth ventricle (P=0.02).
      By multivariate analysis, stepwise logistic regression revealed that
      hydrocephalus was the only independent prognostic factor for poor outcome
      (P<0.001). Postoperative 48-hour GCS score was better than the preoperative score
      by use of paired-sample t test (P<0.001). CONCLUSIONS: Hydrocephalus is the most
      important predictor of poor outcome. External ventricular drainage response for
      hydrocephalus was good in the present study, whereas an early decision should be
      made regarding preoperative neurological condition.

PMID- 11340234
TI  - Cortical neurogenesis in adult rats after transient middle cerebral artery
      occlusion.
AB  - BACKGROUND AND PURPOSE: This study explored the possible occurrence of newly
      generated nerve cells in the ischemic cortex of adult rats after middle cerebral
      artery occlusion and reperfusion. METHODS: Nine- to 10-week-old male Wistar rats
      were subjected to 2 hours of middle cerebral artery occlusion by the monofilament
      method. Rats received repeated intraperitoneal injections of the cell
      proliferation-specific marker 5-bromodeoxyuridine (BrdU) after stroke induction.
      Brain sections were processed for immunohistochemistry with an avidin-biotin
      complex-alkaline phosphatase and/or -peroxidase method. Brain sections processed
      with double-immunofluorescent staining were further scanned by confocal
      microscopy. RESULTS: Interspersed among the predominantly newly formed glial
      cells, some cells were double labeled by BrdU and 1 of the neuron-specific
      markers, Map-2, beta-tubulin III, and Neu N, at 30 and 60 days after stroke
      onset. These cells were randomly distributed throughout cortical layers II
      through VI, occurring with highest density in the ischemic boundary zone. Three
      dimensional confocal analyses of BrdU and the neuron-specific marker Neu N
      confirmed their colocalization within the same cortical cells. CONCLUSIONS: This
      study suggests that new neurons can be generated in the cerebral cortex of adult
      rats after transient focal cerebral ischemia. Cortical neurogenesis may be a
      potential pathway for brain repair after stroke.

PMID- 11340235
TI  - Enhanced expression of Iba1, ionized calcium-binding adapter molecule 1, after
      transient focal cerebral ischemia in rat brain.
AB  - BACKGROUND AND PURPOSE: Iba1 is a novel calcium-binding protein and is
      specifically expressed in microglia in the brain. It has been suggested that Iba1
      plays an important role in regulation of the function of microglia. In the
      present study we examined time-dependent Iba1 expression after transient middle
      cerebral artery occlusion and characterized microglial activation in various
      brain regions. METHODS: Rat middle cerebral artery occlusion was induced by the
      intraluminal filament technique. After 1.5 hours of transient ischemia, Iba1
      expression was examined by immunohistochemical and immunoblot analyses. The
      microglial activation in association with ischemic severity was characterized by
      double immunostaining with other specific markers. RESULTS: In the peri-ischemic
      area, heavily Iba1 immunoreactive cells rapidly appeared at 3.5 hours after
      reperfusion. Immunoreactivity was further increased and peaked at 7 days. In the
      ischemic core, round Iba1-positive cells, which may be blood-borne monocytes,
      appeared from 24 hours and reached a peak at 4 to 7 days. Double immunostaining
      revealed that activated microglia in the peri-ischemic area upregulated Iba1
      expression but were negative for the macrophage marker ED1. ED1-positive cells
      were clearly restricted to the ischemic core. CONCLUSIONS: These findings suggest
      the following: (1) Iba1 expression may be associated with microglial activation
      in ischemic brain, and Iba1 immunostaining can be useful to evaluate the
      pathophysiological roles of activated microglia in ischemic injury. (2)
      Expression of ED1 antigen is strictly restricted to severe ischemic damage,
      whereas activated microglia in the peri-ischemic area showed Iba1 upregulation
      without ED1. Therefore, microglia may exhibit difference of antigenicity in the
      severity of ischemic brain injury.

PMID- 11340236
TI  - Bradykinin mediates the acute effect of an angiotensin-converting enzyme
      inhibitor on cerebral autoregulation in rats.
AB  - BACKGROUND AND PURPOSE: In patients with stroke and long-standing hypertension,
      the autoregulation curve of cerebral blood flow (CBF) shifts toward higher blood
      pressure levels. Angiotensin-converting enzyme (ACE) inhibitors reduce blood
      pressure and shift the autoregulation curve back to normal in hypertensive
      patients. ACE inhibitors have 2 major pharmacological properties: they inhibit
      both the production of angiotensin II and the breakdown of kinins. Hence, we
      investigated whether the effect of an ACE inhibitor on the lower limit of CBF
      autoregulation is mediated by the potentiation of bradykinin-mediated
      vasodilatation. METHODS: In 28 male Sprague-Dawley rats, CBF was measured by
      laser-Doppler flowmetry during stepwise controlled hypotension. The lower limit
      of CBF autoregulation was defined as the mean arterial pressure at which CBF
      decreased by 20% of the baseline value. The rats were treated with an ACE
      inhibitor, captopril, in the captopril group; a bradykinin BK2-receptor
      antagonist, Hoe140, in the Hoe140 group; and both agents in the captopril+Hoe140
      group. Other rats served as a control group. The lower limits of CBF
      autoregulation were compared among the 4 groups. RESULTS: In the captopril group,
      the lower limit of CBF autoregulation was 43+/-8 mm Hg (mean+/-SD), which was
      significantly lower than that in the control group (57+/-14 mm Hg). Inhibition of
      bradykinin abolished the effect of captopril on the lower limit of CBF
      autoregulation. Hoe140 alone had no significant effect on the lower limit of CBF
      autoregulation. CONCLUSIONS: These results suggest that the shift of the lower
      limit of CBF autoregulation by captopril is mediated, at least in part, by
      bradykinin.

PMID- 11340237
TI  - Neuroprotection by the selective cyclooxygenase-2 inhibitor SC-236 results in
      improvements in behavioral deficits induced by reversible spinal cord ischemia.
AB  - BACKGROUND AND PURPOSE: Cyclooxygenase-2 (COX-2), an enzyme that is induced in
      the central nervous system after various insults, has been localized to neurons
      and in cells associated with the cerebral vasculature, where it may be involved
      in the inflammatory component of the ischemic cascade. COX-2 is part of the
      initial reaction that involves the arachidonic acid cascade, which produces
      molecules that support an inflammatory response. The present study evaluated the
      pharmacological effects of a specific long-acting COX-2 inhibitor, SC-236, in a
      reversible rabbit spinal cord ischemia model using clinical rating scores
      (behavioral analysis) as the primary end point. METHODS: SC-236 was administered
      (10 to 100 mg/kg SC) 5 minutes after the start of occlusion to groups of rabbits
      exposed to ischemia induced by temporary (10 to 40 minutes) occlusion of the
      infrarenal aorta. Behavioral analysis, which allowed for the calculation of an
      ET(50) value representing the duration of ischemia (minutes) associated with a
      50% probability of resultant permanent paraplegia, was conducted 18 and 48 hours
      later. A drug was determined to be neuroprotective if it prolonged the ET(50)
      significantly compared with the appropriate control group. RESULTS: Since SC-236
      is not readily soluble in aqueous solutions, it was dissolved in 100% dimethyl
      sulfoxide (DMSO) for subcutaneous administration. Therefore, the vehicle-treated
      control group consisted of rabbits given an equal volume of DMSO without drug. In
      the DMSO-treated control group, the ET(50) assessed 18 hours after initiation of
      aortal occlusion was 18.84+/-3.19 minutes. In contrast, treatment with 100 mg/kg
      of SC-236 given 5 minutes after the start of occlusion prolonged the ET(50) of
      the group significantly to 30.04+/-3.55, an effect that was still evident 48
      hours later. In addition, lower doses of the drug (10 and 50 mg/kg) also showed a
      trend for an increase in ET(50). SC-236 (100 mg/kg) did not significantly alter
      body temperature after a subcutaneous injection. CONCLUSIONS: The present study
      suggests that COX-2 plays an important role in the ischemic cascade of events
      that translate into ischemia-induced behavioral deficits and furthermore that
      selective COX-2 inhibitors may be useful in the treatment of ischemic stroke to
      improve behavioral functions.

PMID- 11340238
TI  - Delayed neuroprotective effect of insulin-like growth factor-i after experimental
      transient focal cerebral ischemia monitored with mri.
AB  - BACKGROUND AND PURPOSE: Insulin-like growth factor (IGF) treatment has been shown
      to have trophic and neuroprotective effects in vitro and in vivo in different
      lesion models. IGF-I has potent neuroprotective effects after hypoxic-ischemic
      injury and global ischemia. The role of IGF-I in focal cerebral ischemia is only
      partially understood. Therefore, in the present study, we evaluated, by applying
      MRI monitoring, whether a clinically relevant systemic administration of IGF-I
      can achieve a long-lasting neuroprotective effect. METHODS: Male Wistar rats
      underwent transient occlusion of the right middle cerebral artery for 1 hour by
      using the suture occlusion model. Animals then were intraventricularly treated
      with 33.33 microg IGF-I/d for 3 days (group A, the IGF-I group [n=13]; group B,
      the placebo group [n=14]) or subcutaneously treated with 200 microg IGF-I/d for 7
      days (group D, the IGF-I group [n=10]; group E, the placebo group [n=10]). Groups
      C and F served as sham-operated controls (n=5 and n=3, respectively). Treatment
      was begun 30 minutes after occlusion of the middle cerebral artery.
      Subcutaneously treated animals underwent MRI studies (diffusion-weighted imaging,
      perfusion imaging, and T2-weighted imaging) beginning 60 minutes after vessel
      occlusion at 6 hours and at days 1, 2, 5, and 7 after ischemia. The animals were
      weighed and neurologically assessed daily (rating scale ranged from 0, indicating
      no deficit, to 5, indicating death). On the third day (intraventricular trial)
      and on the seventh day (subcutaneous trial), animals were euthanized, and brain
      sections were stained with triphenyltetrazolium chloride. RESULTS: The mean
      infarct volume was 52.9+/-25.2 mm(3) in intraventricularly treated animals versus
      146.4+/-62.2 mm(3) in control animals (P<0.01) and 42.2+/-17.9 mm(3) in
      subcutaneously IGF-I-treated animals versus 73.1+/-38.1 mm(3) in control animals
      (P<0.05). Apparent diffusion coefficient-derived lesion volume at 60 minutes
      after occlusion was 40.4+/-23.7 mm(3) versus 38.3+/-19.3 mm(3) (P=NS), increased
      to 168.3+/-49.55 mm(3) versus 105.5+/-33.8 mm(3) (P<0.05) at 24 hours, and then
      decreased to 55.8+/-30.3 mm(3) versus 23.3+/-20.2 mm(3) (P<0.05) for control and
      IGF-I-treated animals, respectively. The T2-weighted-derived ischemic lesion
      volume at 24 hours after occlusion was 236+/-49.2 mm(3) versus 115.9+/-56.8 mm(3)
      (P<0.05) and decreased to 115.9+/-26.2 mm(3) versus 75.7+/-35.8 mm(3) (P<0.05) at
      day 7 for control and IGF-I-treated animals, respectively. The relative regional
      cerebral blood volume was reduced to 50% before reperfusion in all regions of
      interest except for region of interest 1 (vessel territory of anterior cerebral
      artery), recovered during reperfusion, but was not different between the control
      and the growth factor-treated group at any imaging time point. There was no
      significant difference in weight loss. There was less neurological deficit after
      ischemia in intraventricularly and subcutaneously IGF-I-treated animals compared
      with control animals (P<0.05). CONCLUSIONS: Continuous treatment with
      intraventricularly and subcutaneously administered IGF-I achieved a long-lasting
      neuroprotective effect as early as 24 hours after ischemia as measured by MRI.
      Therefore, IGF-I may represent a new approach to the treatment of focal cerebral
      ischemia.

PMID- 11340239
TI  - Glutamate, interleukin-6, and early clinical worsening in patients with acute
      stroke.

PMID- 11340240
TI  - Coagulopathies in ischemic stroke.

PMID- 11340241
TI  - Re: Anticardiolipin antibodies are not an independent risk factor for stroke.

PMID- 11340242
TI  - Revisiting the question, "is the acetazolamide test valid for quantitative
      assessment of maximal cerebral autoregulatory vasodilation?".

PMID- 11340243
TI  - Proinflammatory cytokines and glutamate in acute stroke.

PMID- 11340244
TI  - Stroke Nursing Committee: addressing a special need of the Council of
      Cardiovascular Nursing.

PMID- 11340246
TI  - Immunohematological findings in myelodysplastic syndrome.
AB  - BACKGROUND: Few immunohematological studies have been done in myelodysplastic
      syndrome (MDS). METHODS: Twenty-nine MDS patients were retrospectively evaluated
      with a direct antiglobulin test (DAT), antibody screening, serum electrophoresis
      and immunoelectrophoresis. Clinical and laboratory studies (hemoglobin level,
      reticulocyte count, DHL, total and indirect bilirubin) were done simultaneously,
      as well as the French-American-British subtype and bone marrow biopsy findings.
      RESULTS: Alloantibodies were demonstrated in 17 patients (58.6%), autoantibodies
      in 10 (34.4%) patients and cold agglutinin in 18 (62%) patients. DAT was mediated
      by only IgG in 8 patients (80%), by IgG and C3 in 1 patient (10%) and by IgG, IgA
      and C3 in 1 (10%) patient. No hemolytic disease occurred in patients with
      autoantibodies. Increased serum gammaglobulin was observed in 16 (54.4%)
      patients. There was no correlation between the incidence of allo-/autoantibodies
      and the gammaglobulin level (p = 0.937) and the presence of lymphocyte
      infiltrates in bone marrow biopsies (p = 0.156). No significant difference was
      observed when the incidence of autoantibodies and number of red blood cell
      transfusions were compared (p = 0.334). Patients with refractory anemia and
      refractory anemia with ringed sideroblasts subtypes had a higher incidence of
      allo-/autoantibodies than other MDS subtypes (p = 0.03). CONCLUSION: Patients
      with MDS, in particular refractory anemia and refractory anemia with ringed
      sideroblasts have a high incidence of allo- and autoantibodies, probably related
      to intrinsic immune disorder, without clinical or laboratory hemolysis.

PMID- 11340247
TI  - Immunological evaluation of patients with beta-thalassemia major.
AB  - Abnormalities in the immune system and zinc homeostasis in patients with beta
      thalassemia major (TM) have been reported. Since zinc ion is essential for the
      efficiency of the immune system and is required to induce biological activity to
      thymulin (Zn-FTS), a biochemically defined thymic hormone, we investigated the
      plasma levels of zinc and both active thymulin (Zn-FTS) and total zinc saturable
      thymulin (Zn-FTS+FTS) in 18 patients with TM aged between 2 and 31 years and 22
      normal controls of the same age. Inhibitory molecules anti-thymulin and the
      distribution of lymphocyte subsets were also analyzed. Patients with TM presented
      significantly lowered plasma zinc and thymulin levels when compared to normal
      subjects. The significant enhancement of the active form of the hormone after
      zinc addition in vitro suggests that low thymulin values found in TM are due not
      to a thymic failure in synthesizing and secreting the thymic hormone, but a
      defect in zinc saturation of the hormone. An impairment of cell subset
      distribution was also demonstrated. This study shows that zinc and thymulin
      deficiency contribute to the complex mechanisms underlying immune dysfunction in
      TM.

PMID- 11340248
TI  - Increased frequency and specific reactivity of serum antinuclear antibodies in
      patients with nonimmune chronic idiopathic neutropenia of adults.
AB  - This study describes the frequency of serum organ-specific and organ-nonspecific
      autoantibodies in 157 patients with nonimmune chronic idiopathic neutropenia of
      adults (NI-CINA). Forty-two age- and gender-matched volunteers were used as
      controls. We found that patients with NI-CINA had increased frequency of
      antinuclear antibodies (ANA) compared to controls (33.1 vs. 9.5%, p = 0.0025),
      and that ANA positivity inversely correlated with the number of circulating
      neutrophils (r = -0.2765, p < 0.0001). Speckled pattern of reactivity was seen in
      84.6% of ANA-positive patients, and diffuse pattern in the remaining 15.4%.
      Patients had also increased levels of circulating immune complexes compared to
      controls (3.30 +/- 2.41 vs. 1.70 +/- 1.19 microg/ml, p = 0.0042), which inversely
      correlated with the number of circulating neutrophils (r = -0.2405, p = 0.0154)
      but not with the titer of ANA positivity. No significant differences were found
      between the patients and the normal controls in the frequency of positive tests
      for antibodies to dsDNA, Sm, nRNP, SSA, SSB and Scl-70 antigens, or for parietal
      cell antibodies, anti-neutrophil cytoplasmic antibodies (ANCA), anti-cardiolipin
      and anti-thyroid antibodies. Serum levels of rheumatoid factor, C-reactive
      protein (CRP) and complement factors C3 and C4 ranged within normal limits in the
      patients studied, but a highly significant correlation was noted between the
      levels of CRP and ANA positivity (r = 0.3936, p < 0.0001). These findings are
      suggestive of a chronic inflammation in NI-CINA patients which provides the
      antigenic stimulus for ANA production, and they further support our previously
      reported suggestion for the possible involvement of such a low-grade chronic
      inflammatory process in the pathogenesis of neutropenia in the affected subjects.

PMID- 11340249
TI  - Expansion of CD4+CD16+ blood monocytes in patients with chronic renal failure
      undergoing dialysis: possible involvement of macrophage colony-stimulating
      factor.
AB  - A novel subpopulation of blood monocytes coexpressing CD16 antigen and low levels
      of CD14 antigen (CD14+CD16+ monocytes) has recently been identified, and
      expansion of these CD14+CD16+ monocytes has been reported under some pathological
      conditions. In this study, we examined the immunophenotype of blood monocytes in
      patients with chronic renal failure (CRF) who were undergoing hemodialysis (HD, n
      = 52) or continuous ambulatory peritoneal dialysis (CAPD, n = 36) using two-color
      immunofluorescence flow cytometry. The percentage and absolute number of
      CD14+CD16+ monocytes were significantly higher (p < 0.001) in both HD and CAPD
      patients compared with those in healthy control subjects. We also determined the
      plasma concentrations of hematopoietic growth factors and cytokines using an
      enzyme-linked immunosorbent immunoassay. The plasma levels of macrophage colony
      stimulating factor (M-CSF) were markedly increased in both HD and CAPD patients
      relative to the normal controls. The plasma M-CSF levels correlated significantly
      with the number of CD14+CD16+ monocytes in the whole group of subjects. These
      findings suggest that elevated endogenous M-CSF levels may participate in the
      expansion of CD14+CD16+ monocytes in CRF patients undergoing dialysis.

PMID- 11340250
TI  - Avascular necrosis of the hip in children with sickle cell disease and high Hb F:
      magnetic resonance imaging findings and influence of alpha-thalassemia trait.
AB  - Avascular necrosis (AVN) of the hip is a common cause of morbidity in sickle cell
      disease (SCD). Its prevalence increases with age and predisposing factors include
      coexistent alpha-thalassemia trait, frequent vaso-occlusive crisis and a high
      hematocrit (Hct). SCD is relatively mild among Kuwaiti patients because of their
      elevated Hb F levels, but a subset exists with severe recurrent vaso-occlusive
      crises. We carried out a prospective magnetic resonance imaging (MRI) study of
      the hip in a group of patients being followed in the Pediatric Hematology clinics
      of Al-Mubarak and Al-Amiri Hospitals. The association of AVN with age, frequency
      of hospitalization, alpha-thal trait, steady-state Hb, Hct, Hb F, WBC and
      platelet counts was investigated. MRI was carried out with a 1.5-tesla GE unit
      with a super-conducting magnet. Thirty patients (19 males, 11 females) (23 SS and
      7 SbetaThal) were studied. Their ages ranged from 6 to 17 years, with a mean of
      9.8 +/- 3.5 years, and Hb F from 11 to 35% with a mean of 22.8 +/- 5.7%. Among
      the SS patients, 11 (47.8%) had coexistent alpha-thal trait (-3.7-kb deletion). A
      total of 8 (26.7%) patients (6 SS and 2 SbetaThal) had varying degrees of
      osteonecrosis of the hip. Four (36.4%) of the 11 SS patients with alpha-thal
      trait and 2 (16.7%) of those without alpha-thal trait had osteonecrosis. This
      difference is, however, not statistically significant (chi(2) = 0.3, p = 0.5).
      While there was also no significant difference in the mean age and hematological
      parameters (Hb, Hct, Hb F, WBC, platelets), the SS patients with osteonecrosis
      had a significantly higher number of hospitalizations for vaso-occlusive crisis
      in the preceding 3 years than those without osteonecrosis.

PMID- 11340251
TI  - Investigation of ethnic neutropenia by assessment of bone marrow colony-forming
      cells.
AB  - Healthy individuals with African ancestry have lower neutrophil counts than
      Caucasians. It has previously been postulated that this was consequent on either
      a diminished bone marrow granulocyte reserve or an altered distribution of
      neutrophils between the circulating and marginated granulocyte pools. Recent
      indirect evidence supports the former hypothesis. In this study we have compared
      the number of granulocyte plus granulocyte-macrophage colony-forming units (CFUs)
      in the bone marrow of healthy African and Afro-Caribbean subjects with the number
      of CFUs in the bone marrow of healthy age and sex-matched Caucasians. We found
      the group with African ancestry to have significantly fewer CFUs than the
      Caucasian group. There was no evidence of any qualitative difference between the
      CFUs of the two ethnic groups: they showed similar sensitivity to granulocyte
      monocyte colony stimulating factor and similar enhancement of growth when
      cultured with a larger range of cytokines. These observations suggest that ethnic
      neutropenia observed in those with African ancestry is likely to result from
      reduced numbers of bone marrow progenitor cells in comparison with numbers
      present in Caucasians.

PMID- 11340252
TI  - The activity in ex vivo expansion of cord blood myeloid progenitor cells before
      and after cryopreservation.
AB  - A total of 50 human umbilical cord blood (UCB) samples were studied. The
      hematopoietic stem/progenitor (CD34+) populations were isolated from UCB
      mononuclear cells (MNC) by means of immunomagnetic separation. Double
      immunofluorescent staining of UCB CD34+ cells revealed that there was a high
      proportion (82.33 +/- 4.47%) of CD34+ cells co-expressing CD13, while the
      percentage of CD34+ CD33+ cells was much lower (22.17 +/- 3.35%). In contrast,
      for co-expressing lymphoid differentiation antigens, the proportion of CD34+CD38+
      cells (38.34 +/- 6.09%) was relatively higher than that of CD34+CD10+ cells
      (11.52 +/- 1.24%) or CD34+CD2+ cells (9.84 +/- 2.30%). For stimulating the ex
      vivo expansion of UCB progenitor cells, no single hematopoietic growth factor
      (HGF) was efficacious when used alone, while combination of 4 HGFs, such as GM
      CSF, G-CSF, IL-3, and SCF could induce a 55-fold increase in the myeloid
      progenitor cells, day-14 CFU-GM, in a short term of 7 days' liquid culture.
      Cryopreservation of UCB as MNC preparations at -196 degrees C could
      satisfactorily retain the number and activity of CD34+ cells. After thawing, a
      high recovery rate of about 80% CD34+ cells was obtained. When suspended in
      liquid cultures containing a combination of 4 HGFs, as shown above, the frozen
      cord blood progenitor cells could be well expanded, reaching a >50-fold increase
      in day-14 CFU-GM, which was very similar to that of the fresh UCB samples. In
      addition, a similar result was also seen in CFU-GEMM, indicating that after
      cryopreservation the recovered UCB progenitor cells retain an intact clonogeneic
      ability capable of efficiently responding to hematopoietic growth factors for ex
      vivo expansion.

PMID- 11340254
TI  - Nodal gamma/delta T cell lymphoma in complete remission following allogeneic bone
      marrow transplantation from an HLA-matched unrelated donor.
AB  - Gamma/delta T cell lymphoma is very rare, and usually occurs as an extranodal
      tumor. We describe the case of a 16-year-old Japanese man with an unusual nodal
      gamma/delta T cell lymphoma with generalized lymphadenopathy and bone marrow
      involvement. No tumor involvement was observed in the liver, spleen, or nasal
      cavity. Examination for surface antigens on lymphoma cells revealed a unique
      phenotype, positive for CD3 and T cell receptor (TCR) gamma/delta, but negative
      for CD2. Genotypic analysis revealed the tumor to be of monoclonal origin and
      characterized by TCR gamma-chain gene rearrangement, but there was no
      rearrangement of the TCR beta-chain gene. Our patient's tumor responded to
      combination chemotherapy and subsequent allogeneic bone marrow transplantation
      from an HLA-matched unrelated donor. He has remained well and free of disease for
      35 months.

PMID- 11340253
TI  - Detection of minimal residual disease in a patient having acute myelogenous
      leukemia with t(16;21)(p11;q22) treated by allogeneic bone marrow
      transplantation.
AB  - A 29-year-old woman having acute myelogeneous leukemia-M1 subtype with the
      chromosomal abnormality t(16;21)(p11;q22) is presented. Complete blood count at
      onset showed a hemoglobin level of 7.2 g/dl, a platelet count of 48 x 10(9)/l,
      and a white blood cell count of 161.2 x 10(9)/l with 99% blasts and 1%
      lymphocytes. Bone marrow aspiration revealed massive proliferation of blasts that
      were positive for CD13, CD33, CD34, CD56 and myeloperoxidase, and negative for
      other T-cell, B-cell and monocytic markers. After achieving complete remission
      following conventional chemotherapy, she received an HLA-matched bone marrow
      transplantation (BMT) from her sibling after conditioning with busulfan,
      etoposide and cyclophosphamide. However, 9 months later, the leukemia relapsed as
      a painful extramedullary mass in her left femur. In spite of intensive re
      induction chemotherapy, she died of progressive disease and sepsis. Although we
      could not detect the TLS/FUS-ERG fusion transcripts by reverse transcriptase
      polymerase chain reaction in pre-BMT remission phase, they were clearly
      detectable in bone marrow cells obtained 6 months after transplantation with no
      translocation detected by conventional cytogenetics. We consider that even high
      dose chemotherapy with BMT may not be effective in the eradication of this type
      of leukemia, and that the detection of minimal residual disease possibly
      contributes to the better planning of the therapeutic strategy.

PMID- 11340255
TI  - Non hypoxia-related splenic infarct in a patient with sickle cell trait and
      infectious mononucleosis.
AB  - Splenic infarction in patients with sickle cell trait is usually related to
      hypoxic conditions, while non-hypoxia-related infarcts are extremely rare. We
      report on a case of a 17-year-old male patient, living at sea level, who
      developed a severe left upper quadrant abdominal pain during the course of a
      febrile episode. On physical examination he had a mildly palpable but extremely
      painful spleen. A spleen scan revealed 2 areas of impaired radionucleide
      distribution. Hepatic enzymes were moderately increased and the IgM anti-EBV
      antibodies positive. Hemoglobin electrophoresis revealed the presence of 42% of
      hemoglobin S. A probable diagnosis of splenic infarction was established in a
      patient with sickle cell trait, during the course of infectious mononucleosis.
      The patient was treated symptomatically. The conditions of splenic congestion
      induced by the EBV infection and the high-grade fever may have contributed to
      splenic sequestration and subsequent infarcts.

PMID- 11340256
TI  - Pericytes: cell biology and pathology.
AB  - Pericytes are perivascular cells with multifunctional activities which are now
      being elucidated. The functional interaction of pericytes with endothelial cells
      (EC) is now being established, using current molecular and cytochemical
      techniques. The detailed morphology of the pericyte has been well described.
      Pericytes extend long cytoplasmic processes over the surface of the EC, the two
      cells making interdigitating contacts. At points of contact, communicating gap
      junctions, tight junctions and adhesion plaques are present. Pericytes appear to
      show both structural and functional heterogeneity. The coverage of EC by
      pericytes varies considerably between different microvessel types and the
      location of pericytes on the microvessel is not random but appears to be
      functionally determined. Interaction between pericytes and EC is important for
      the maturation, remodelling and maintenance of the vascular system via the
      secretion of growth factors or modulation of the extracellular matrix. There is
      also evidence that pericytes are involved in the transport across the blood-brain
      barrier and the regulation of vascular permeability. The long-standing view that
      pericytes are the microvessel equivalent of larger vessel smooth muscle cells and
      are contractile is being reassessed using current methods. An important role for
      pericytes in pathology, and neuropathology in particular, has been indicated in
      hypertension, diabetic retinopathy, Alzheimer's disease, multiple sclerosis and
      CNS tumour formation.

PMID- 11340257
TI  - The dynamic in vivo distribution of bone marrow-derived mesenchymal stem cells
      after infusion.
AB  - Bone marrow-derived mesenchymal stem cells (MSCs) have the potential to
      differentiate along different mesenchymal lineages including those forming bone,
      cartilage, tendon, fat, muscle and marrow stroma that supports hematopoiesis.
      This differentiation potential makes MSCs candidates for cell-based therapeutic
      strategies for mesenchymal tissue injuries and for hematopoietic disorders by
      both local and systemic application. In the present study, rat marrow-derived
      MSCs were ex vivo culture-expanded, labeled with (111)In-oxine, and infused into
      syngeneic rats via intra-artery (i.a.), intravenous (i.v.) and intraperitoneal
      cavity (i.p.) infusions. In addition, for i.a. and i.v. infusions, a vasodilator,
      sodium nitroprusside, was administered prior to the cell infusion and examined
      for its effect on MSC circulation. The dynamic distribution of infused MSCs was
      monitored by real-time imaging using a gamma camera immediately after infusion
      and at 48 h postinfusion. After 48 h, radioactivity in excised organs, including
      liver, lungs, kidneys, spleen and long bones, was measured in a gamma well
      counter and expressed as a percentage of injected doses. After both i.a. and i.v.
      infusion, radioactivity associated with MSCs was detected primarily in the lungs
      and then secondarily in the liver and other organs. When sodium nitroprusside was
      used, more labeled MSCs cleared the lungs resulting in a larger proportion
      detected in the liver. Most importantly, the homing of labeled MSCs to the marrow
      of long bones was significantly increased by the pretreatment with vasodilator.
      These results indicate multiple homing sites for injected MSCs and that the
      distribution of MSCs can be influenced by administration of vasodilator.

PMID- 11340258
TI  - Immunohistochemical detection of myogenic cells in muscles of fetal and neonatal
      lambs.
AB  - Previous studies have implied that myonuclei accumulation in a muscle is more
      important than myofibre number in the determination of muscle size in
      fetal/neonatal lambs. However, due to the lack of a reliable marker, the role of
      myogenic precursor nuclei (satellite cells) in myofibre hypertrophy in late fetal
      and postnatal life is not well understood. In this study, MyoD was shown to be a
      useful marker for actively proliferating satellite cells in both fetal and
      neonatal lambs. MyoD was used to determine whether there were differences in the
      number of actively proliferating satellite cells between single and twin
      fetuses/neonates, which may explain at least some of the difference in myofibre
      size observed near birth. Eighteen single-bearing and 9 twin-bearing Coopworth
      ewes were randomly assigned to one of three slaughter groups (100, 120 and 140
      days of gestation). The remaining ewes were kept on pasture until 20 days
      postpartum at which time 4 single and 4 twin lambs were sacrificed. Twin
      fetuses/neonates had lower body weights and muscle weights compared to singles.
      Lower muscle weights in the twins were associated with smaller myofibre cross
      sectional areas and lower total nuclei numbers and myogenic precursor cell
      numbers per muscle in selected hind-limb muscles. These results indicate that
      myofibre hypertrophy in late gestation and early postnatal life is related to
      myogenic precursor cell number which may have important implications for growth
      potential of the growth-restricted fetus.

PMID- 11340259
TI  - Optimization of hepatocyte spheroid formation for hepatic tissue engineering on
      three-dimensional biodegradable polymer within a flow bioreactor prior to
      implantation.
AB  - We hypothesize that in vitro conditioning of hepatocytes within biodegradable
      poly-L-lactic acid (PLLA) polymer matrices prior to implantation may increase
      hepatocyte survival and function after transplantation. The purpose of this study
      was to optimize the culture conditions of hepatocytes in a pulsatile flow
      bioreactor. PLLA discs were seeded with rat hepatocytes in a concentration of
      2.5, 5, 10, 20 and 40 x 10(6) cells/ml. Seeded discs were exposed to recirculated
      perpendicular flow of 0, 7, 15, 24, 32, 52 ml/min of supplemented Williams'
      Medium E and harvested after 6 days in flow culture. Only under flow conditions
      the hepatocytes formed spheroidal aggregates (SphA) of 50-260 microm in diameter
      with a liver-like morphology and active metabolic function. The number of SphA
      was examined by phase contrast microscopy and the reductive enzyme function of
      the hepatocytes was tested using MTT. Hematoxylin and eosin histology showed
      vital hepatocytes within the SphA less than 200 microm in diameter but central
      necrosis in the SphA exceeding this size. Immunohistochemical staining confirmed
      albumin production of hepatocytes within the SphA. The optimal cell seeding
      concentration was 10 x 10(6) cells/ml with a flow speed of 24 ml/min. SphA of
      hepatocytes cultured with this flow bioreactor method may prove useful as a
      functional unit for tissue engineering of an in vivo liver substitute.

PMID- 11340260
TI  - Regulation of embryonic chick insulin cells: effect of retinoic acid and insulin
      like growth factor 1.
AB  - We are interested in the regulation of early pancreatic differentiation,
      particularly with regard to factors that enhance insulin cell proliferation. Both
      retinoic acid and insulin-like growth factor 1 (IGF-1) are known to be important
      in the proliferation and differentiation of insulin cells. Individually, they
      have the ability to increase the proportion of insulin cells when added to
      cultures of chick dorsal pancreatic buds. The aim of this study was to define the
      action of retinoic acid (RA) in combination with IGF-1 on the proportion of
      insulin cells. The dorsal pancreatic bud of 5-day-old chick embryos was excised
      and the endodermal component, with minimal adherent mesenchyme, was explanted
      onto Matrigel. RA (10(-6) M) and IGF-1 (50 ng/ml) were added to Ham's F12 culture
      medium containing transferrin (5 microg/ml) and selenium (10(-10) M) (F12.TS).
      Control explants were cultured in F12.TS alone or in F12.TS containing dimethyl
      sulphoxide (DMSO) [F12.TS (DMSO)]. After 7 days in culture, insulin and glucagon
      cells were localized immunocytochemically; numbers of insulin cells were
      expressed as a percentage of insulin plus glucagon cell counts. Addition of RA
      plus IGF-1 to the medium increased the proportion of insulin cells markedly
      (23.43%) compared with the proportions in control explants (11.3% with F12.TS
      (DMSO), 13.2% with F12.TS). This increase represents a more than twofold increase
      in the proportion of insulin cells over that of control explants.

PMID- 11340261
TI  - Quantitative immunohistochemical analysis of the expression of CD31 during lung
      development in the rat.
AB  - The CD31 antigen, known also as the platelet/endothelial cell adhesion molecule
      1, has been shown to be a good marker for monitoring the formation of the
      vasculature in mammals. Available evidence suggests that the expression of CD31
      is regulated during embryonal and fetal development. The aim of the present study
      was to evaluate the changes in the expression of CD31 during the development of
      the rat lung. We studied samples of lung tissue from rat fetuses (17, 19 and 21
      days after conception), newborns (1, 3, 5, 7, 14 and 21 days after birth) and
      adult animals. The tissue samples from rats in the various age groups were
      divided into sets, with all age groups being represented in every set. After
      immunohistochemical localization of the antigen, the amount of chromogen
      deposited after the immunoreaction (defined in terms of optical density; OD) was
      evaluated by image analysis in the various sets. Measurements were obtained twice
      from each set, and the results were reproducible (paired t test, alpha = 0.05).
      We subjected the results of measurements from all sets to an analysis of variance
      (ANOVA). The amount of chromogen (OD) decreased from fetal day 19 to 5 days after
      delivery and then increased again. The decrease in the level of expression of
      CD31 on days 3 and 5 after delivery was significant (p < 0.0001).

PMID- 11340262
TI  - The Pars tuberalis of the monkey (Macaca fascicularis) hypophysis: cell types and
      hormone expression.
AB  - The pars tuberalis (Pt) of most mammalian species contains specific cells which
      are structurally and functionally different from the pars distalis (Pd) cells. Pt
      specific cells possess melatonin receptors and reveal morphological changes
      dependent on the duration of the photoperiod. Furthermore, in hamsters the
      transmission of photoperiodic stimuli to the endocrine system is influenced by
      melatonin, an effect which is likely to be mediated by Pt-specific cells. In
      monkeys, however, only little is known about this cell type. Therefore, we
      studied the ultrastructural differentiation of Pt-specific cells and describe the
      expression of different hormones and their mRNA by immunohistochemistry and in
      situ hybridization. Apparently the Pt consists of (1) cells similar to
      gonadotropic cells of the Pd, (2) folliculostellate cells and (3) a cell
      population which is morphologically and functionally clearly distinct from all
      other cell types found in the Pd. Morphologically they resemble the Pt-specific
      cells found in other species. Regarding the expression of secretory products
      there is evidence that they transcribe and translate the beta-TSH subunit.
      Although there is a strong signal for the mRNA of the common alpha-chain, protein
      staining is much weaker. POMC mRNA is expressed in the Pt while there is no
      evidence for PRL mRNA. The present results lead to the conclusion that the Pt of
      the monkey contains Pt-specific cells which express different hormonal subunits
      as was already shown for other species. In context with previous findings of
      melatonin receptors in the monkey Pt further investigations are necessary to
      establish the possible role of Pt-specific cells in the photoperiod-dependent
      generation of endocrine rhythms.

PMID- 11340263
TI  - Ultrastructural and quantitative immunohistochemical changes induced by
      nonsteroid antiandrogens on pituitary gonadotroph population of prepubertal male
      rats.
AB  - Specific blockade of the androgen receptor by the nonsteroid antiandrogens
      flutamide and Casodex has proven to be a useful tool for studying androgens in
      vivo. The aim of the present study was to investigate the effect of antiandrogen
      administration at the pituitary level by evaluating the ultrastructural changes
      in gonadotrophs, in correlation with the quantitative immunohistochemical
      findings, and by comparing these alterations with the effect of androgen
      deprivation by castration either with or without subsequent androgen replacement.
      Male Sprague-Dawley rats (23 days old) were grouped as follows: (1) controls, (2)
      flutamide-injected (10 mg/rat/day), (3) Casodex-injected (10 mg/rat/day), (4)
      castrated, and (5) castrated plus androgen-replaced (dihydrotestosterone
      propionate; 40 microg/rat/day). Groups were sacrificed after 10 days of
      maintenance under each condition. Pituitaries were processed for both light and
      electron microscopy. Serial sections (4 microm) were obtained at different levels
      and immunostained by means of the primary murine monoclonal antibodies anti-FSH
      and anti-LH and a peroxidase-mediated EnVision System (Dako). Volume density,
      cell density and mean cell area were measured with an image analysis system
      (Imaging Technology, Software Optimas 5.2). The mean cell area (p < 0.001) and
      the volume density (p < 0.05) increased significantly in the flutamide- and
      Casodex-treated groups as well as the castrated group of FSH and LH cells. On the
      other hand, androgen replacement in the castrated rats, however, reduced in both
      parameters related to control animals. The cell density of FSH-secreting cells
      was increased (p < 0.05) in the Casodex and flutamide treatment as well as
      castrated group. The cell density of LH-secreting cells was augmented (p < 0.05)
      in the Casodex-treated group, while there was no increase in such parameter with
      flutamide and castration. The ultrastructure of all groups showed two types of
      gonadotrophs. Type I cells contained large (300-500 nm) and small (150-200 nm)
      secretory granules, while type II cells were smaller, and exhibited only small
      granules (100-200 nm). Flutamide-treated, Casodex-treated and castrated groups
      presented a decreased number of secretory granules with some exocytotic profiles,
      well-developed rough endoplasmic reticulum and an expanded Golgi complex of both
      types of cells. The gonadotrophs from the castrated group exhibited numerous
      mitochondria with electron-dense ring-shaped laminar figures, while in the
      castrated plus androgen-replaced rats only a few mitochondria had similar changes
      to those observed in castrated animals, as a possible residual alteration.
      Finally, the gonadotrophs from flutamide-treated rats showed mitochondrial
      alterations with clear areas and isolated electron-dense laminar figures. In
      summary, we conclude that lack of androgen reaction through the effects of
      nonsteroid antiandrogens and castration on prepubertal rats produced a
      hypertrophia-hyperplasia of the FSH cells, and hypertrophia of LH-secreting
      cells, with marked alterations at the ultrastructural level suggestive of a
      hyperstimulation stage.

PMID- 11340264
TI  - Stereological study of normal and apoptotic cell populations in the adrenal gland
      in calves.
AB  - Morphometrical features of the adrenal gland in calves were assessed using
      stereological methods for normal and apoptotic cells. Adrenal glands were
      obtained from calves (n = 16) after they were slaughtered in a commercial
      abattoir. Quantitative data of nuclear size showed the highest values in the
      noradrenaline-storing region for all parameters, whereas the nuclei of the zona
      fasciculata were significantly larger than those of the other cortical regions.
      Data of nuclear size and shape of apoptotic cells reflected their morphometrical
      features; as expected, a notable decrease in the nuclear size and a more
      irregular shape were found in apoptosis with respect to the normal nuclei in all
      adrenal regions. The volume fraction data supplied the percentage of the adrenal
      gland occupied by each histological zone, highlighting the zona fasciculata as
      being the most extensive one. A significant increase in V(V)(nucl/tis),
      S(V)(nucl/tis), and Nv(nucl/tis) was observed in cortical regions with respect to
      the medullar regions. A comparison between normal and apoptotic nuclei indicated
      a highly significant decrease in V(V)(nucl/tis), S(V)(nucl/tis), and Nv(nucl/tis)
      for the apoptotic nuclei in all the adrenal zones. The apoptotic nuclei figures
      found in all the adrenal regions suggest that a process of cell renovation
      occurred in all the zones, although the higher number of apoptosis in zona
      reticularis is in agreement with previous results that have pointed out this zone
      as being a cell senescence region. The results of discriminant analyses gave the
      parameter required and the percentage of correct classifications for
      discriminating between normal nuclei, between apoptotic nuclei and between normal
      and apoptotic nuclei.

PMID- 11340265
TI  - Endothelin-1 and big-endothelin concentrations are elevated in liver graft tissue
      during cold storage and reperfusion.
AB  - Endothelin (ET) and its precursor big-ET were synchronously analyzed by RIA in
      liver biopsies and systemic plasma during porcine orthotopic liver
      transplantation (OLT) before graft harvesting (phase A), after cold storage
      (phase B), and early (phase C) and late reperfusion (phase D). Tissue and plasma
      concentrations were correlated with length of survival and reperfusion. Increased
      tissue ET/big-ET levels were already detected during phase B (ET: 46 +/- 20; big
      ET: 245 +/- 119 pg/mg cytosolic protein) and remained elevated in phase C (ET: 49
      +/- 16; big-ET: 306 +/- 144 pg/mg) compared to baseline (ET: 32 +/- 13; big-ET:
      185 +/- 164 pg/mg; p < 0.05). In phase D, a rapid concentration decline was
      detected (ET: 36 +/- 26; big-ET: 163 +/- 138 pg/mg). Systemic ET levels were
      elevated in phase B (3.4 +/- 3.0 pg/ml), C, (2.8 +/- 1.2 pg/ml) and D (2.6 +/-
      2.0 pg/ml), compared to baseline (1.7 +/- 1.1 pg/ml; p < 0.05). ET/big-ET
      kinetics in liver tissue and systemic plasma showed analogous characteristics.
      Intrahepatic ET accumulation during storage and early reperfusion could be of
      relevance for harvest-related disturbances of hepatic microcirculation.

PMID- 11340266
TI  - Expression of Bcl-2 family reduces apoptotic hepatocytes after excessive
      hepatectomy.
AB  - Excessive hepatectomy often causes fatal hepatic failure, but the mechanism is
      unknown. We used a novel protocol of partial 90 and 95% hepatectomy (PHx) to
      investigate this mechanism in 2 groups of rats. The 90% PHx rats survived, but
      the 95% PHx animals died of hepatic failure. In the latter, cytokine (interleukin
      6, tumor necrosis factor-alpha) levels and the apoptotic hepatocyte count
      increased, and there were few mitotic cells. By contrast, in the 90% PHx rats,
      the mitotic cell count increased, and more anti-apoptotic Bcl-xL protein was
      expressed. These results demonstrate that expression of Bcl-xL protein as an anti
      apoptotic factor or regeneration factor contributes to survival after 90% PHx.
      Using an adenovirus vector, the human bcl-2 gene (hbcl-2) was therefore
      transfected to DA rat livers where it was efficiently expressed, and then 95% PHx
      was performed. Liver damage was decreased and the apoptotic cell count decreased
      too, but the rats died. We concluded that transfection of the hbcl-2 gene partly
      prevents cytotoxicity (apoptosis), but cannot ensure survival. Thus, some other
      factor is required (e.g., a regeneration stimulator) to maintain life in these
      models.

PMID- 11340267
TI  - Angiogenic effects of suture biomaterials. An experimental study in rats.
AB  - Angiogenesis is a limiting step of inflammation and wound healing. Although
      laboratory tests for the evaluation of the angiogenetic effects of biomaterials
      are available, no investigations have been performed. In this study we examine
      the angiogenetic effect of suture biomaterials in the rat mesenteric window
      model. Absolute controls had laparotomy only, controls had mesenteric window
      wounding, test groups had the insertion of either a thread of collagen,
      polyglactin 910, polyglycolic acid salt, silk or of a titanium clip. We
      considered the percentage area of the mesenteric window covered by neovessels.
      After 7 days, negligible angiogenesis was found in absolute controls, significant
      angiogenesis in controls, collagen, polyglactin 910 and polyglycolic acid salt
      treated rats, without differences between treatments. A significant increase of
      angiogenesis in comparison to the control group was found in rats treated with
      silk and titanium. Ultramicroscopy of the neovessels showed specific changes of
      their architecture in titanium-treated rats. In conclusion, angiogenesis during
      wound healing is differently influenced by the suture material used. Silk and
      titanium stimulated angiogenesis in a different way.

PMID- 11340268
TI  - Natural course of the functional and morphological changes in canine autogenous
      arterial graft.
AB  - BACKGROUND: We examined the time course of endothelium-dependent and -independent
      responses in reversed autogenous arterial grafts during regeneration and tissue
      repair processes after arterial grafting in dogs. MATERIALS AND METHODS:
      Autogenous arterial grafts implanted in the canine femoral artery were removed,
      cut into rings and suspended in organ chambers for isometric tension recording on
      the 1st, 3rd, 7th, 14th and 28th days after implantation. Electron-microscopic
      examination on the 1st, 3rd,7th, 14th and 28th days after transplantation was
      also performed. Control arteries were taken from nonsurgically treated femoral
      arteries. RESULTS: Acetylcholine (ACh) and A23187 caused endothelium-dependent
      relaxations in arterial grafts throughout the study. Although endothelium
      dependent relaxations to ACh and A23187 on the 3rd day after transplantation were
      only significantly impaired compared to those of control, they were similar to
      the control within 1 week after grafting. Smooth muscle relaxations in response
      to sodium nitroprusside in arterial grafts throughout the study were comparable
      with those of control arteries. No apparent intimal thickening of the arterial
      grafts was observed. Electron microscopy scanning revealed mild endothelial cell
      damage in implanted autogenous arterial grafts on the 1st or 3rd day after
      grafting. Seven to 14 days after grafting, the endothelial cell layer appeared to
      be normal. CONCLUSIONS: It was observed that the endothelial function remained
      intact and there was an absence of intimal thickening in the arterial grafts.
      These observations may explain the improved patency of autogenous arterial grafts
      compared to the vein grafts in aortocoronary revascularization.

PMID- 11340269
TI  - Glycosaminoglycans of normal veins and their alterations in varicose veins and
      varicose veins complicated by thrombophlebitis.
AB  - The aim of the study was to examine the content and molecular differentiation of
      glycosaminoglycans (GAGs) in the wall of varicose veins. The studied material
      consisted of normal, varicose veins and varicose veins complicated by
      thrombophlebitis collected during operations on 26 patients. In the wall of
      varicose veins the mean GAGs' content as well as the content of sulphated GAGs,
      except heparan sulphate was increased, whereas the amount of hyaluronic acid was
      decreased. Furthermore, the increased quantitative ratio between sulphated and
      nonsulphated GAGs was demonstrated. The results indicate an evident extracellular
      matrix remodelling in the wall of varicose veins particularly those complicated
      by thrombophlebitis, that is characterised by alterations in the content and
      molecular differentiation of GAGs.

PMID- 11340270
TI  - Increased monocyte activation in elderly patients after surgical stress.
AB  - OBJECTIVE: To investigate age-related changes in the host response to surgical
      stress. The clinical course, serum interleukin-6 (IL-6) levels, monocyte
      production of tumor necrosis factor-alpha (TNF-alpha), and monocyte expression of
      CD11b/CD18 were used as markers of the systemic response. METHODS: Patients with
      gastric cancer, undergoing distal gastrectomy were divided into 2 groups: >75
      years of age (elderly group) and < or =75 years of age (young group). Serum IL-6
      levels, TNF-alpha production and CD11b/CD18 expression by monocytes, and the
      postoperative clinical course were compared between the 2 groups. RESULTS: TNF
      alpha production by lipopolysaccharide-stimulated monocytes and CD11b/CD18
      expression on monocytes after surgical stress were significantly higher in the
      elderly than in the young group. Moreover, serum IL-6 levels on the first
      postoperative day in the elderly group were significantly higher than those in
      the young group. The incidence and duration of systemic inflammatory response
      syndrome (SIRS) were significantly greater in the elderly than in the young
      group. CONCLUSIONS: The activation of monocytes and hypercytokinemia occur
      readily after surgical stress in the elderly and may therefore contribute to SIRS
      and increased susceptibility to postoperative complications.

PMID- 11340271
TI  - The value of pre-emptive analgesia in the treatment of postoperative pain after
      laparoscopic cholecystectomy.
AB  - BACKGROUND AND AIM: Postoperative pain is an important surgical problem. Recent
      studies in pain pathophysiology have led to the hypothesis that with pre
      operative administration of analgesics (pre-emptive analgesia) it may be possible
      to prevent or reduce postoperative pain. This study was planned to investigate
      the efficacy of pre-emptive analgesia on postoperative pain after laparoscopic
      cholecystectomy. METHODS: 45 patients undergoing laparoscopic cholecystectomy
      were randomized into three groups. Bupivacaine was injected into the area of skin
      incision before trocar entry and after trocar removal in group 1 and 2,
      respectively; however, this procedure was not applied to the control group. The
      pain score of the patients was evaluated by the visual analogue scale (VAS) at 1,
      4, 12( )and 24 h after surgery. The daily analgesic requirement was evaluated in
      terms of diclophenac sodium (Diclomec, Abdi Ibrahim, 75 mg) intake/day.
      Analgesics were given to the patients whose VAS was 5 or higher. RESULTS: While
      there was no significant difference in VAS scores between group 1 and 2, the mean
      pain scores of these two groups were found to be significantly lower than of the
      control group although the analgesic requirement of the patients in each group
      was not statistically significant. CONCLUSION: Pre-emptive analgesia is as
      effective as postsurgical local anaesthesia in reducing postoperative pain.

PMID- 11340274
TI  - Latent prostatic carcinoma. Proceedings of a symposium. Hamburg, Germany,
      November 2-4, 2000.

PMID- 11340275
TI  - Epidemiology of prostate cancer.

PMID- 11340272
TI  - The relationship between revascularisation and osteogenesis in fresh or
      demineralised bone grafts.
AB  - Bone formation generally depends on adequate blood flow. Failure of bone grafts
      has been attributed to delayed revascularisation of the graft. We compared the
      relationship between revascularisation and osteogenesis, evaluated as entrapment
      of (141)Ce-labelled microspheres and uptake of (85)Sr, respectively, in fresh or
      demineralised syngeneic bone grafts 3 weeks after heterotopic implantation in
      rats. Whereas a moderately high linear correlation between (85)Sr and (141)Ce
      radioactivity was found both in the (intact) host iliac bone (r = 0.75, p =
      0.0001) and implanted fresh syngeneic grafts (r = 0.50, p = 0.001), no
      correlation could be demonstrated in demineralised grafts (r = 0.09, p = 0.6).
      The results may indicate differences in the mechanisms of vascularisation and
      osteogenesis in the grafts used fresh or after demineralization but are, at
      present, difficult to fully explain.

PMID- 11340276
TI  - The role of intraductal carcinoma in the natural history of prostatic
      adenocarcinoma.

PMID- 11340277
TI  - Morphogenesis of prostate cancer.

PMID- 11340278
TI  - The molecular pathogenesis of prostate cancer: focus on the earliest steps.

PMID- 11340280
TI  - Familial aggregation of prostate cancer management while waiting for the
      identification of hereditary prostate cancer genes.

PMID- 11340279
TI  - Hereditary prostate cancer in germany.

PMID- 11340281
TI  - Secondary cancers in the prostate do not determine PSA biochemical failure in
      untreated men undergoing radical retropubic prostatectomy.

PMID- 11340282
TI  - Expectant management of prostate cancer with curative intent.

PMID- 11340283
TI  - Detection and characterization of early prostate cancer by six systematic
      biopsies and fine needle aspiration cytology in prostates from bladder cancer
      patients.

PMID- 11340284
TI  - High-grade prostatic intraepithelial neoplasia in cystoprostatectomy specimens.

PMID- 11340285
TI  - Randomized screening trial for prostate cancer in Finland.

PMID- 11340286
TI  - Tumor volume is a valid surrogate endpoint for defining clinically significant
      prostate cancers.

PMID- 11340287
TI  - Latent prostate carcinoma in a screened population.

PMID- 11340288
TI  - Human prostate cancer blocks the generation of dendritic cells from CD34+
      hematopoietic progenitors.

PMID- 11340289
TI  - Latent carcinoma of the prostate.

PMID- 11340290
TI  - Consideration of low PSA cut-off levels to optimize the detection of curable
      prostate cancer.

PMID- 11340291
TI  - Role of hK2, free PSA, and complexed PSA measurements in the very early detection
      of prostate cancer.

PMID- 11340292
TI  - Diagnosis, characterization and potential clinical relevance of prostate cancer
      detected at low PSA ranges.

PMID- 11340293
TI  - IGHV3-associated restriction fragment length polymorphisms confer susceptibility
      to bullous pemphigoid.
AB  - OBJECTIVE: To determine whether the immunoglobulin heavy chain genes contribute
      to the occurrence of bullous pemphigoid (BP), polymorphisms of both the
      immunoglobulin constant IGHC and variable IGHV groups were studied in 100
      Caucasian BP patients and 143 ethnically matched healthy individuals. METHODS: To
      analyze the restriction fragment length polymorphism (RFLP) of the IGHG constant
      locus, a genomic immunoglobulin gamma 3 probe which detects polymorphisms in the
      gamma constant genes was hybridized to BstEII- or BamHI/SacI-digested germline
      DNA, while IGHV3 subgroup polymorphism was analyzed by hybridizing a cloned VH3
      probe to EcoRI-digested DNA. RESULTS: No difference in the frequencies of the
      genotypes defined by the constant probe was observed between patients and
      controls. Analysis of the RFLP obtained with the VH3 probe showed that within the
      range of 4.5 and 1.5 kb, the observed band pattern was composed of 8 monomorphic
      and 7 polymorphic bands. Among the latter, 4 allowed to define 10 different
      restriction patterns. One pattern was shown to be significantly less frequent in
      patients than in controls. CONCLUSION: IGHV3 polymorphism might be a factor
      conferring susceptibility to BP.

PMID- 11340294
TI  - Genotyping interleukin-10 high and low producers with single-tube bidirectional
      allele-specific amplification.
AB  - A simple bidirectional allele-specific PCR method is described for determining
      the -1082 A and G alleles in the interleukin-10 (IL-10) promoter region. This
      polymorphism is associated with IL-10 production capacity, and it is thus
      interesting to see whether different infectious and autoimmune conditions are
      associated with it. With our method, the A and G alleles may be studied
      simultaneously in a single PCR reaction, as amplification of the different
      alleles is performed by using 3'-mismatched and partly overlapping allele
      specific upstream and downstream primers around the -1082 site. The fast and
      simple method described here is especially suitable for large-scale association
      studies.

PMID- 11340295
TI  - An aberrant form of CD59 derived from HeLa cells.
AB  - We isolated a CD59 cDNA from a HeLa cell library which encoded a mutated form of
      CD59, having a single base substitution (G to T) that changed Arg55 to Met. Since
      this mutation occurred in the vicinity of the putative active site of CD59, we
      expressed the aberrant form of the protein in Chinese hamster ovary cells in
      order to test for effects upon function. We found that the mutation did not
      influence complement inhibitory activity of CD59. However, the epitopes
      recognised by the function-blocking CD59 monoclonal antibodies BRIC229 and YTH
      53.1 were significantly affected. The G to T substitution caused loss of an Mnl I
      restriction site which permitted PCR-RFLP analysis. All of 52 human subjects
      studied, and our in-house HeLa cells, were homozygous for the normal CD59
      sequence, indicating that the altered sequence was not due to normal variation in
      the general population. Therefore this mutation probably arose spontaneously in
      the HeLa cell line used to generate the commercially obtained cDNA library.

PMID- 11340296
TI  - Interferon-alpha induces transient suppressors of cytokine signalling expression
      in human T cells.
AB  - The suppressors of cytokine signalling (SOCS) proteins comprise a newly
      identified family of negative feedback regulators of cytokine signalling. SOCS
      expression is differentially induced upon cytokine stimulation in different cell
      types. Here we show that interferon-alpha (IFNalpha) is a potent inducer of SOCS
      expression in human T cells, as high expression of CIS, SOCS-1, SOCS-2, and SOCS
      3 was detectable after IFNalpha stimulation. After 4 h of stimulation, CIS, SOCS
      1, and SOCS-3 expression had returned to baseline levels, whereas SOCS-2
      expression had not declined. In contrast, after IL-2 induction neither CIS, SOCS
      1, nor SOCS-2 expression levels declined after 6 h. In conclusion, we provide the
      first evidence that IFNalpha induces SOCS expression in human T cells. Moreover,
      we show that IFNalpha and IL-2 induce distinct patterns of expression kinetics,
      suggesting that dynamic changes in cytokine sensitivity might be mediated via
      induction of SOCS expression with different kinetics in T cells.

PMID- 11340297
TI  - Gab2 is phosphorylated on tyrosine upon interleukin-2/interleukin-15 stimulation
      in mycosis-fungoides-derived tumor T cells and associates inducibly with SHP-2
      and Stat5a.
AB  - Cutaneous T cell lymphomas (CTCLs) often show abnormal interleukin-2 (IL-2)
      receptor signaling. In this study, we investigated the role of Gab2, a recently
      identified adaptor molecule involved in IL-2 receptor signaling in CTCLs. We show
      that Gab2 was transiently phosphorylated by tyrosine in human mycosis fungoides
      (MF) tumor T cells upon IL-2 stimulation and that SHP2 as well as Stat5a
      associated inducibly with Gab2. IL-15, but not IL-4, also induced tyrosine
      phosphorylation of Gab2, suggesting that the IL-2 receptor beta-chain is
      important for IL-2-induced Gab2 phosphorylation. Preincubation of cells with the
      Src family kinase inhibitor, PP1, surprisingly increased the IL-2- and IL-15
      induced tyrosine phosphorylation of Gab2, indicating that an Src family kinase
      member negatively regulates IL-2 receptor signaling in MF T cells. Thus, although
      Gab2 seems to function normally in MF T cells compared to normal T cells, Gab2
      itself might be abnormally regulated by an Src family kinase.

PMID- 11340298
TI  - Development of single-chain Fv fragments from a human anti-double-stranded DNA
      antibody to study the influence of somatic mutations on antigen binding.
AB  - OBJECTIVE: The monoclonal IgG anti-double-stranded (ds) DNA antibody 32B9,
      obtained from a patient with systemic lupus erythematosus, was found to be
      encoded by somatically mutated immunoglobulin genes. We examined the input of
      several somatic mutations into antibody specificity and affinity. METHODS: Five
      single-chain (sc) Fv fragments [variable domain of the heavy chain (V(H))-linker
      variable domain of the light chain (V(L))] derived from 32B9 were constructed and
      expressed in Escherichia coli. These scFv fragments contained V(H) or V(L)
      fragments, differing in the somatic mutation pattern. The antigen binding
      features of the 32B9 IgG were compared with the corresponding scFv fragments, and
      the binding to DNA of all fragments was analyzed by ELISA. Binding constants to
      dsDNA were determined by surface plasmon resonance and ELISA. RESULTS: The scFv
      32B9 reflected the binding features of the 32B9 IgG. Independently of the somatic
      mutations, all scFv fragments bound to dsDNA in ELISA. The affinity data
      indicated that the mutations studied had only a marginal effect on affinity
      maturation of the 32B9. DISCUSSION: We discuss the approach to constructing scFv
      fragments as a tool to study autoantibody maturation.

PMID- 11340299
TI  - Nomenclature of the human immunoglobulin heavy (IGH) genes.
AB  - 'Nomenclature of the Human Immunoglobulin Heavy (IGH) Genes', the 16th report of
      the 'IMGT Locus in Focus' section, provides the first complete list of all the
      human IGH genes. The total number of human IGH genes per haploid genome is 170
      176 (206-212 genes, if the orphons and the processed gene are included), of which
      77-84 genes are functional. IMGT/Human Genome Organization (HUGO) gene names and
      definitions of the human IGH genes on chromosome 14q32.33, processed gene on
      chromosome 9 and IGH orphons on chromosomes 15 and 16 are provided with the gene
      functionality and the number of alleles, according to the rules of the IMGT
      Scientific chart, with the accession numbers of the IMGT reference sequences and
      with the accession ID of the Genome Database GDB and NCBI LocusLink databases, in
      which all the IMGT human IGH genes have been entered. The tables are available at
      the IMGT Marie-Paule page of IMGT, the international ImMunoGeneTics database
      (http://imgt.cines.fr:8104) created by Marie-Paule Lefranc, Universite
      Montpellier II, CNRS, France.

PMID- 11340300
TI  - Pericyte regulation of renal medullary blood flow.
AB  - Pericytes are contractile smooth muscle-like cells that surround descending vasa
      recta (DVR) and provide their capability for vasomotion. The importance of the
      medullary pericyte derives from the role of DVR to distribute most or all of the
      blood flow from juxtamedullary cortex to the renal inner and outer medulla.
      Physiological processes that are likely to be influenced by pericyte constriction
      of DVR include the urinary concentrating mechanism and pressure natriuresis.
      Oxygen tensions in the medulla are low, so that subtle variation of pericyte
      vasomotion might play a role to abrogate hypoxia and prevent insult to the
      medullary thick ascending limb of Henle. Known vasoconstrictors of DVR include
      angiotensin II, endothelins, norepinephrine, acetylcholine, and adenosine.
      Vasodilators include prostaglandin E2, adenosine, acetylcholine, bradykinin, and
      nitric oxide.

PMID- 11340301
TI  - Long-term ammonium chloride or sodium bicarbonate treatment in two models of
      polycystic kidney disease.
AB  - Administration of ammonium chloride aggravates, while short-term administration
      of sodium or potassium bicarbonate lessens the development of polycystic kidney
      disease in Han:SPRD rats. We have conducted studies to determine whether the
      protection afforded by the administration of sodium bicarbonate is sustained and
      prevents development of uremia during chronic administration and whether the
      effects of the administration of ammonium chloride and sodium bicarbonate are
      also observed in a different model of polycystic kidney disease, the CD1-pcy/pcy
      mouse. We found that chronic administration of 200 mM sodium bicarbonate to
      Han:SPRD rats inhibited cystic enlargement and prevented the subsequent
      development of interstitial inflammation, chronic fibrosis, and uremia. We also
      found that, while the administration of ammonium chloride has similar effects in
      Han:SPRD rats and CD1-pcy/pcy mice, the administration of sodium bicarbonate is
      only protective in the Han:SPRD rats. This probably reflects differences in these
      models (predominately involvement of proximal tubules in Han:SPRD rats and of
      collecting ducts and distal tubules in pcy/pcy mice) and the different location
      and nature of the renal metabolic responses to the administration of acid or
      alkaline load.

PMID- 11340302
TI  - Inhibition of TNF-alpha, induced cytokine and adhesion molecule. Expression in
      glomerular cells in vitro and in vivo by transcription factor decoy for NFkappaB.
AB  - Activation of certain cytokines and adhesion molecules has been postulated being
      involved in the pathogenesis of experimental and human glomerulonephritis. In
      this study, we examined whether the transcription factor, nuclear factor kappaB
      (NFkappaB), mediated the expression of these genes involved with the inflammatory
      response of mesangial cells by using transcription factor decoy
      oligodeoxynucleotides (ODN) to block NFkappaB binding to the promoter site of its
      target genes. We hypothesized that the NFkappaB decoy ODN can inhibit the
      coordinated activation of cytokines and adhesion molecules induced by TNF-alpha.
      Increased binding activity of NFkappaB induced by TNF-alpha was effectively
      blocked by the NFkappaB decoy ODN. TNF-alpha stimulated CAT expression, which was
      significantly inhibited by transfection of NFkappaB, but not by scrambled decoy
      ODN. Of importance, NFkappaB, but not scrambled decoy ODN, significantly
      attenuated the increase in RNA and protein levels of IL-1alpha, IL-1beta, IL-6,
      ICAM-1 and VCAM-1 induced by TNF-alpha assessed by RT-PCR. Moreover, in vivo
      transfection of NFkappaB decoy ODN inhibited expressions of these cytokines and
      adhesion molecules induced by TNF-alpha injection. These results suggest a novel
      therapeutic strategy for the treatment of glomerulonephritis using decoy ODN to
      block the binding of NFkappaB, inhibiting the coordinated transactivation of the
      key cytokines and adhesion molecules, and thereby suppressing the inflammatory
      process.

PMID- 11340303
TI  - Troglitazone stimulates basolateral rheogenic Na+/HCO3- cotransport activity in
      rabbit proximal straight tubules.
AB  - Thiazolidinedione derivatives, new insulin-sensitizing antidiabetic agents, are
      expected to have potential clinical use. Since these drugs cause edema in a
      variable proportion of patients, we examined whether troglitazone (Tro) has
      direct action on Na+ transport of rabbit proximal straight tubule perfused in
      vitro. For this purpose, we measured basolateral membrane voltage (V(B)) by
      conventional microelectrode techniques and intracellular pH (pH(i)) by
      microscopic fluorescence spectrophotometry with a pH-sensitive fluorescent dye,
      2', 7'-bis-2-carboxyethyl-5-carboxyfluorescein. Tro at 50 microM in the bath
      significantly depolarized both transepithelial voltage and V(B). To examine
      whether the basolateral rheogenic Na+/HCO3- cotransport activity is affected by
      Tro, we observed V(B) deflection upon abrupt 10-fold decrease in bath HCO3- in
      the absence and presence of Tro. The apparent transference number of HCO3-
      (tHCO3), as calculated from the V(B) deflection, was significantly greater in the
      presence of Tro (50 microM) than that seen in its absence. Tro caused cell
      acidification and increased the intracellular acidification rates (dpH(i)/dt)
      upon abrupt 10-fold decreases in bath HCO3- and Na+ concentrations. The
      stimulatory effects of Tro on tHCO3 and dpH(i)/dt were dose dependent between 5
      and 50 miccroM, but they were unaffected at 0.5 microM. From these results, we
      conclude that Tro acts on the proximal straight tubule and stimulates the
      basolateral rheogenic Na+/HCO3- cotransport activity. The stimulatory action of
      Tro may partly account for edema formation.

PMID- 11340304
TI  - Molecular mechanisms by which iron induces nitric oxide synthesis in cultured
      proximal tubule cells.
AB  - Nitric oxide (NO) levels are increased after exposure of cultured proximal tubule
      cells (PTC) to non-haem iron, potentially contributing to PTC injury in disease
      states associated with increased iron exposure, including proteinuric renal
      disease. The mechanisms underlying this observed increase were investigated.
      After 3 h exposure to 400 microM nitrilotriacetate (NTA)-Fe, inducible nitric
      oxide synthase (iNOS) mRNA expression was significantly increased, with a
      corresponding increase in iNOS protein after 12 h. The nuclear binding activity
      of NFkappaB with 400 microM NTA-Fe was increased, and pyrrolidine dithiocarbamate
      (PDTC), an antioxidant inhibitor of NFkappaB, prevented both activation of
      NFkappaB and NO production in response to NTA-Fe. Inhibition of protein tyrosine
      kinase reduced iNOS mRNA, iNOS protein levels and NO production in response to
      NTA-Fe. The effect of tyrosine kinase inhibition on NFkappaB activation was
      variable, with herbimycin but not genistein having an inhibitory effect.
      Activation of either protein kinase A or C increased iNOS mRNA and protein
      levels, and NO production in response to NTA-Fe, whereas only the protein kinase
      C activator phorbol dibutyrate (PDBu) had a stimulatory effect on NFkappaB
      activation. The protein kinase A activator forskolin did not alter iron-induced
      activation of NFkappaB. These data suggest that the observed increase in NO
      production by PTC in response to iron is due to increased transcription of iNOS.
      The transcriptional regulation of this response is complex and involves NFkappaB,
      protein tyrosine kinase and the protein kinases A and C.

PMID- 11340305
TI  - Regulation of tubular cell MCP-1 production by intracellular ions: a role for
      sodium and calcium.
AB  - Proximal tubule cells (PTC) in chronic renal disease produce chemokines which
      cause renal interstitial inflammation, and also transport more Na+ than normal.
      To investigate whether these two events might be related, monocyte
      chemoattractant protein-1 (MCP-1) production was examined in rat PTC in primary
      culture. Amiloride reduced, while ouabain increased levels of MCP-1 mRNA and
      protein. Amiloride reduced MCP-1 in cells stimulated with ouabain,
      lipopolysaccharide (LPS) or albumin. Intracellular Na+ rose with ouabain, but not
      LPS or albumin. Effects of amiloride, ouabain, LPS and albumin were abrogated by
      sodium-free but not chloride-free culture medium, and were not explained by
      changes in intracellular pH. Intracellular Ca2+ rose with ouabain, LPS or albumin
      and sodium-free medium. BAPTA-AM reduced intracellular Ca2+ and MCP-1 mRNA levels
      in unstimulated cells, and cells stimulated with ouabain, LPS or albumin. Thus,
      amiloride and ouabain may alter tubular cell MCP-1 by changing intracellular Na+,
      with secondary changes in intracellular Ca2+, whereas stimulation by LPS and
      albumin may involve Ca2+ directly.

PMID- 11340306
TI  - Decreased glomerular expression of agrin in diabetic nephropathy and podocytes,
      cultured in high glucose medium.
AB  - AIM: A decrease in glomerular heparan sulfate (HS) proteoglycan (PG), without
      apparent decrease in HSPG core protein expression, has been reported to occur in
      diabetic nephropathy (DN). In most studies however, agrin, the major HSPG core
      protein in the glomerular basement membrane, has not been studied. This prompted
      us to study the glomerular expression of agrin in parallel to the expression of
      HS-glycosaminoglycans (GAG) in biopsies of patients with DN. Furthermore, the
      influence of glucose on agrin production in cultured podocytes and the expression
      of agrin in fetal kidneys was investigated. METHODS: Cryostat sections of renal
      biopsies from patients with DN (n = 8) and healthy controls (HC, n = 8), were
      stained for agrin and HS-GAG. Sections of fetal kidneys were double stained for
      agrin and CD35 or CD31. Stainings were performed by indirect immunofluorescence
      (IIF). The production of agrin by cultured human podocytes was tested by ELISA
      and IIF. RESULTS: The expression of agrin, detected by AS46, was significantly
      reduced in biopsies from patients with DN compared to HC (p < 0.01). Similar
      findings were observed when monoclonal antibody JM72 was used (p < 0.05). In
      addition, a significant reduction in the glomerular expression of HS-GAG was
      detected with JM403 in these patients (p < 0.01). Agrin is expressed in cultured
      podocytes, the expression hereof was reduced when the cells were cultured in the
      presence of 25 mM D-glucose (p < 0.01). In biopsies of human fetal kidneys,
      glomerular expression of agrin coincided with the expression of CD31. In early
      stages of glomerular differentiation there was a strong staining for agrin and
      CD31 while CD35 was only slightly positive. CONCLUSIONS: Our data argue against a
      selective dysregulation in HSPG sulfation in DN, but suggest a pivotal role for
      hyperglycemia in the downregulation of agrin core protein production.

PMID- 11340307
TI  - 1,25-dihydroxyvitamin D3 differentially regulates IL-1alpha-stimulated IL-8 and
      MCP-1 mRNA expression and chemokine secretion by human primary proximal tubular
      epithelial cells.
AB  - Beside its role in calcium homeostasis, 1,25-D3 modulates multiple immunological
      functions in cells of the immune system. In tubular epithelial cells, it
      increases the expression of HLA-DR and ICAM-1 molecules. Since production of
      chemokines, such as IL-8 and MCP-1, by tubular epithelial cells is crucial for
      the inflammatory response in acute transplant rejection and interstitial
      nephritis, we tested whether 1,25-D3 influences the production of IL-8 and MCP-1
      by primary human tubular epithelial cells (TEC). For chemokine detection we used
      enzyme-linked immunosorbent assays. We differentiated between chemokine secretion
      directed to the apical and basolateral environment by using cell culture inserts
      as a model for the tubular basement membrane. mRNA of IL-8 and MCP-1 after
      stimulation of TEC with IL-1alpha and/or 1,25-D3 was isolated and compared by
      competitive RT-PCR. We found that basolateral production of IL-8 was higher than
      luminal secretion. 1,25-D3 (10(-8) M) alone and in combination with IL-1alpha
      suppressed IL-8 production after 48 h. Basolateral compared to luminal MCP-1
      secretion was higher after stimulation either with IL-1alpha alone or combined
      with 1,25-D3. After 72 h, 1,25-D3 enhanced the IL-1alpha-stimulated MCP-1
      secretion. Increased IL-8 mRNA expression after stimulation with IL-1alpha was
      suppressed by coincubation with 1,25-D3, while MCP-1 mRNA synthesis was enhanced
      by 1,25-D3 alone and in combination with IL-1 alpha. We conclude that 1,25-D3
      differently modulates the expression of CXC-chemokine IL-8 and CC-chemokine MCP-1
      by human TEC. The differential effects of 1,25-D3 on renal tubular cytokine
      secretion have to be considered in therapeutic dials on this hormone, e.g. in
      renal transplant rejection.

PMID- 11340308
TI  - Effect of tissue processing on the ability to recover nucleic acid from specific
      renal tissue compartments by laser capture microdissection.
AB  - The anatomic heterogeneity of the nephron poses obstacles to microdissection of
      individual renal compartments for analysis of gene expression. We have
      systematically analyzed the effects of fixation time and nuclear staining on the
      ability to recover nucleic acid from individual renal compartments by laser
      capture microdissection (LCM). Formalin-fixed kidney sections from Wistar rats
      and archival human renal biopsies were used for DNA analysis. From 1 to 10
      individual glomeruli and from 1 to 10 individual proximal tubules were captured
      sequentially onto polymer films. DNA for beta-globin could be amplified by PCR
      from even a single glomerulus or tubule. Optimal conditions for DNA amplification
      were brief (1- or 2-day) formalin fixation. Use of nuclear counterstains,
      including Weigert's hematoxylin, Harris's hematoxylin, Mayer's hematoxylin, or
      methyl green, did not adversely affect the ability to extract and amplify DNA.
      For RNA extraction, glomeruli and tubules were microdissected from renal cryostat
      sections stored for up to 6 months. By RT-PCR, mRNA expression of the glomerulus
      specific gene, Wilms' tumor-1, was identified in as few as 5 microdissected
      glomeruli and of the tubule-specific gene, aminopeptidase N, in as few as 5
      microdissected tubules, with no cross-contamination between renal compartments.
      Our findings indicate that the LCM method can successfully microdissect pure
      glomerular and tubular tissue compartments and that the optimal fixation and
      staining conditions are those employed routinely for renal biopsies, namely
      overnight formalin fixation and hematoxylin counterstain for DNA extraction, and
      cryostat sectioning with hematoxylin counterstain for RNA extraction. The
      specificity of LCM coupled with the sensitivity of RT-PCR should prove a powerful
      tool for the analysis of gene expression in specific renal compartments from
      archival human renal biopsies.

PMID- 11340309
TI  - [Evaluation of in-hospital treatment with naturopathic methods - the
      'Blankenstein model'. Part I: Patients and therapeutic concepts].
AB  - BACKGROUND: In January 1997 the department for naturopathy with 60 beds has been
      established at the Catholic Hospital St. Elisabeth, Blankenstein, and was taken
      into consideration in Northrhine-Westphalia's plan of hospital budgets. AIM: The
      establishment of this department was connected to a scientific evaluation, which
      was performed to check the diagnostic and therapeutic possibilities and limits of
      naturopathic methods applied within the field of inpatient treatment according to
      section sign 39 SGB V. PATIENTS AND METHODS: Besides sociodemographic surveys,
      questions about the ranges of indication and results of treatments as well as the
      analysis of the cost-benefit relation were part of the evaluation. Additionally,
      a subject of the current check was the delimitation towards means of
      rehabilitation or towards ambulant treatments. In order to initiate or to
      continue an open dialog with other model projects on this field, at first the
      therapeutical concept of the department was presented in excerpts. RESULTS: The
      mean age of the patients treated was 57.3 years. In total, 440 of the 618
      patients (71.3%) were capable of gainful employment, which means they were
      between 17 and 65 years old. In three fourths of all examined patients their
      place of residence was in the areas of Essen, Dortmund, and Hagen. Every patient
      had a therapy time of 4.1 h per day in the hospital. In total, 8.7 medicines per
      patient were taken, with an average quantity of 12.9 single doses per day. 97.3%
      of the patients had a second diagnosis, and 91.8% of the patients had 3 or more
      diagnoses. 60% of the patients suffered from rheumatic diseases. In 84.7% of
      these patients the first diagnosis was 'disease of the skeleton and the muscles'.
      Concerning the diagnostic means, electrocardiograms and X-ray examinations as
      well as in-house councils about these means can be named as being characteristic.
      By means of patient groups that have been differentiated by the tracer diagnosis,
      the corresponding therapy standards are explained. These standards have been
      worked out with classical naturopathic treatments, especially in regard to
      rheumatic diseases. DISCUSSION: The application of naturopathic methods within
      the field of inpatient treatment is especially distinguished by the regular use
      of classical naturopathic treatments (especially hydrotherapy), with a high
      therapy density. By establishing standardized therapy concepts, comparisons with
      the ambulant care of chronically ill patients as well as with the results of
      model projects within the field of rehabilitation are made possible.

PMID- 11340310
TI  - [Criteria for assessing benefit with complementary medical methods].
AB  - Criteria for Assessing Benefit with Complementary Medical Methods BACKGROUND: The
      paper was produced by the author at the request of the Swiss Federal Social
      Insurance Department in a broad-based consensus process involving the principal
      parties in the health system, discussed with international experts at a public
      workshop, and finally approved in the form it is presented here by the Services
      Commission of the Federal Home Office on March 12, 1998. It provides a basis for
      assessing the efficacy, suitability and financial viability of complementary
      medical methods in the context of Swiss health insurance legislation. CONTENTS:
      Evidence-based complementary medicine cannot rest entirely on experimental trials
      but needs all available methods of obtaining evidence to arrive at a fair
      assessment, from the empirical judgement of individual medical practitioners to
      randomized double blind trials. In addition to experimental trials, special
      emphasis lies on test methods involving no experimental change in the medical
      intervention and the conditions pertaining to it. In so far as the experimental
      design on which randomized double blind trials are based takes no account of
      factors that are integral to holistic and individualized complementary medical
      treatment (e.g., the individual aspect of the doctor-patient relationship, and
      motivation), other evaluation concepts are needed that will do justice to these
      methods, such as evaluation of the overall clinical situation.The same applies
      when it is a matter not only of the efficacy of a method within the closely
      defined framework of experimental trials but also of its effectiveness in a wider
      context in practice and the context-related situation in the target population
      for the social security system (real world effectiveness). It is important for
      evaluation to be not primarily design-orientated but problem-orientated, with the
      design developed accordingly.

PMID- 11340311
TI  - [On the general basis of naturopathy and complementary medicine].
AB  - On the General Basis of Naturopathy and Complementary Medicine BACKGROUND:
      Naturopathy and complementary medicine are discussed controversially in public:
      On the one hand naturopathy is increasingly accepted by the interested public, on
      the other hand members of the medical community display a critical or even
      rejecting attitude towards naturopathy. Clarification of the terminology and
      methods of medical science as well as of naturopathy is necessary. The goal is
      not only to reestablish the communication between 'classical medicine' and
      naturopathy but also to gain impulses for the health care system from a
      cooperation of both, especially with regard to cost development and the search
      for new solutions and therapies, for example for 'incurable' diseases. PROCEDURE:
      Here we describe the different view of naturopathy on humans and their diseases
      and investigate the current scientific knowledge. Naturopathy often has a
      different, a 'holistic' basis (anthropology), a different therapeutic approach
      (pathogenesis, salutogenesis). RESULTS: The understanding of science in today's
      medicine has its origin in history, therefore it is not only continuously
      changeable but also in need of change. On the one hand new findings from other
      scientific disciplines should be embraced, on the other hand especially medical
      science should react to the acute needs and questions of patients. Naturopathy in
      theory and in applied medicine proves its efficacy (different validities for
      different procedures). It is followed by the search for the principle of
      functioning (extension of science). Starting here, an extended understanding of
      mankind and nature and new models of disease and therapy can be developed. Also,
      medical ethics in the sense of naturopathy would demand as a first step the use
      of agents causing the least possible damage. Only when those agents fail,
      stronger interventions should be chosen. CONCLUSIONS: Due to the necessary
      enhancement of scientific evaluation of naturopathy and the development of
      explanatory models, impulses for better therapy approaches are to be expected.
      Qualitative (new therapy models) and economic (cost reduction) impulses for the
      health care system would be the result.

PMID- 11340312
TI  - [How scientific is medicine? - the health model in medicine and environmental
      sciences].

PMID- 11340313
TI  - [Metaphorical aspects of mistletoe therapy in patients' experiences--a
      qualitative study].
AB  - OBJECTIVE: Mistletoe therapy is an item of research because of its immunological
      features. Nevertheless, mistletoe should be also an item of research because of
      its semiotics. Long before R. Steiner proposed mistletoe as an anticancer drug,
      this plant seemed to have its meaning not by pharmacodynamics but by
      pharmacosemiotics and magic. Thus, metaphorical aspects of mistletoe therapy
      should be described by processing the transcript and paintings from a therapeutic
      group session of cancer patients. Especially the relation between individually
      and historically coded metaphors should be looked at. MATERIAL AND METHODS:
      Sample of this qualitative study is the transcript of a therapeutic session of 12
      female malignoma patients getting mistletoe infusions (Isorel(r)) since 1.5 years
      in a general practitioners' practice. Sequential coding of the transcript,
      inventory of themes, and structural hypothesis are the first steps. The
      structural hypothesis is triangulated by a textual corpus containing
      anthroposophic and ethnographic material; then a grounded theory is made.
      RESULTS: The material is divided. On the one hand, there is a huge amount of
      historically coded, stereotypic metaphors (sun, cancer, ritual). On the other
      hand, 'ritual' seems not only a stereotypic metaphor but also a container of
      individually coded metaphors concerning body experiences (proprioceptive etc.).
      Metaphors from anthroposophy are rare - the metaphors seem to stem from a deeper
      level of ethnographic sources. The whole session has a polyphone narrative
      structure. Categories of semiotics such as icon, index and symbol are only by the
      context of interaction a suitable description for mistletoe's metaphoric
      function. CONCLUSIONS: Problems of bias (denominator problem, valid but not
      reliable) are discussed, and a proposal is made for further forms of
      generalization of the results (semantic differentials). Moreover, it has to be
      asked if different preparations of mistletoe (e.g. lectine standard, draft from
      planta tota) make different halos of metaphors.

PMID- 11340315
TI  - [Influence of reflex zone therapy of the feet on intestinal blood flow measured
      by color Doppler sonography].
AB  - OBJECTIVE: An influence on organ-associated blood flow is considered as a
      possible mechanism of action of reflex zone massage of the feet (FRZM) therapy.
      In the present study we investigated whether changes in intestinal blood flow can
      be achieved by FRZM. MATERIAL AND METHODS: 32 healthy adults (19 women and 13
      men) were randomly assigned to the treatment or the placebo group. Subjects of
      the treatment group received foot massage on the zones assigned to the intestines
      and those of the placebo group received massage on zones unrelated to the
      intestines. Before, during and after FRZM, the blood flow velocity, the peak
      systolic and the end diastolic velocities in the superior mesenteric artery as
      well as the resistive index as a parameter of vascular resistance were
      calculated. RESULTS: During FRZM, in the subjects of the treatment group there
      was a significant reduction in the resistive index (p = 0.021), suggesting an
      increase in the blood flow in the superior mesenteric artery and the subordinate
      vascular system. In contrast, there were no significant changes in the resistive
      index in the subjects of the placebo group. CONCLUSION: The reduction in the
      resistive index observed in the treatment group supports the assumption that FRZM
      improves blood flow in the organs considered to be associated with the specific
      foot zones, at least during the therapy process.

PMID- 11340314
TI  - [Changes of cognitive brain functions in the elderly by Kneipp therapy].
AB  - INTRODUCTION: Pharmacological and nonpharmacological treatment of brain syndrome
      is multifarious. Until now, plain external applications of physical stimuli, as
      used daily in geriatric care, were not explored regarding their influence on
      cognitive brain function. The aim of this randomized cross-over study was to
      examine the influence of dermatoreceptive stimuli on cognitive brain function of
      healty geriatric volunteers. METHODS: 24 healthy volunteers (23 women, 1 man)
      were randomized into 2 groups (cross-over design). Group A (mean age +/- SD: 68.8
      +/- 6.2 years) was treated according to the following regime: at first a 10-12
      degrees C cold stimulus for 10 s (a so-called Kneipp face shower) and afterwards
      a cold wet pack of 10-12 degrees C at the neck for 1 min. Group B (age 69.8 +/-
      5.3 years) was subjected to an identical procedure but with warm
      thermoindifferent temperatures of 34-36 degrees C. After 1 week the two groups
      were interchanged. The parameters of interest were the critical flicker frequency
      (CFF) and the latencies of the event-related P300 potentials of the visually
      evoked potentials (VEP), which can be considered the electroencephalographic
      substrate of the cognitive functional ability. The CFFs and the P300 latencies
      and amplitudes were measured directly before and 10 min after the application of
      the above-mentioned stimuli. Furthermore, the CFFs were recorded a second and
      third time 30 and 60 min later. RESULTS: Following application of cold-water
      stimuli, the CFF increased from (mean +/- SE) 32.55 +/- 0.44 s(-1) to 33.06 +/-
      0.44 s(-1) (p = 0.003) 10 min after the stimulus. 30 min later the CFF was still
      elevated at 32.95 +/- 0.47 s(-1) (p = 0.043). The P300 latencies decreased by
      4.8% (p < 0.001) after cold-water application from 266.5 +/- 5.28 to 253.7 +/-
      4.22 ms. After warm stimuli they increased from 258.69 +/- 3.71 to 266.17 +/-
      5.03 ms (p = 0.01). The P300 amplitudes were elevated by 5% only with the cold
      stimuli (p = 0.004). CONCLUSION: Cold water applied locally to face and neck
      region is able to provoke significant improvements of cognitive abilities.

PMID- 11340316
TI  - [Meaning of health and illness in change: consequences for patient care].
AB  - Consequences for Patient Care Medical science and education is dealing with
      illness, health and healing. But what is health? How does it work? It is a
      paradox that we know a lot about illness, but in general we do not know much
      about the effects how to become healthy, how to restore our health. Other
      sciences gave us more hints for the reasons that are summarized in this article.
      In order to take care for better circumstances in our social and medical system
      we should promote all ways to get better informed patients with a sense of
      responsibility and to give them the right of self-determination. Finally we are
      giving an example how to achieve patients well trained in conserving or in
      restoring their health: 'Strukturiertes Gesundheitstraining'.

PMID- 11340317
TI  - Cerebral Haemorrhage. Parenchymal intracranial haemorrhage.
AB  - While there have been substantial improvements in the management of patients with
      cerebral infarction and there are likely to be further improvements over the next
      decade, the same may not be true for cerebral haemorrhage. Diagnostic facilities
      and neurosurgical techniques have improved but not all patients are benefiting
      from these. The current literature is reviewed. Further controlled trials of the
      utility of modern neurosurgical techniques are urgently required as at present no
      therapeutic intervention holds out hope for these patients other than optimum
      medical management. The main focus must be on prevention.

PMID- 11340318
TI  - Diminished reserve for cerebral vasomotor response to L-arginine in the elderly:
      evaluation by transcranial Doppler sonography.
AB  - BACKGROUND: Nitric oxide is pivotal in endothelially dependent vasodilatory
      regulation. An association of endothelial dysfunction with aging has been
      documented in the forearm and coronary vascular beds. However, the influence of
      aging in the human cerebral circulation, where regulation is particularly
      complex, is incompletely understood. OBJECTIVE: We systematically administered L
      arginine, a precursor of nitric oxide, to evaluate the influence of aging on
      nitric oxide-mediated cerebral vasomotor regulation. METHODS: Among healthy
      volunteers, 20 older subjects (10 men, 10 women; age: 70.2 +/- 2.8 years) and 22
      younger subjects (10 men, 12 women; age: 28.8 +/- 1.9 years) received intravenous
      infusions of L-arginine monochloride (500 mg/kg) over 30 min. Hemodynamic
      parameters were monitored continuously during and after infusion. The cerebral
      vasomotor response was estimated by transcranial Doppler sonography of the right
      middle cerebral artery. RESULTS: Infusion of saline as a control brought little
      change in the mean blood pressure, heart rate or cerebral blood flow velocity in
      either group. On administration of L-arginine, cerebral blood flow velocity
      increased and mean blood pressure decreased. After completion of infusion, both
      parameters rapidly normalized. While reduction of mean blood pressure did not
      differ between older and younger groups, the cerebral circulation in the older
      group showed a blunted, smaller, and more easily saturated vasomotor response
      compared to the younger group, though both groups had similar baseline values.
      CONCLUSION: Our results indicate a diminished nitric oxide-mediated cerebral
      vasomotor response in aging subjects. Additionally, transcranial Doppler
      sonography can be used to reliably evaluate age-related changes in the
      physiologic responses of the human cerebral circulation.

PMID- 11340319
TI  - Changes in bicycle ergometer test performance and survival in men and women from
      50 to 60 and from 70 to 80 years of age: two longitudinal studies in the Glostrup
      (Denmark) population.
AB  - BACKGROUND: During the aging process longitudinal changes for sustained work in
      humans are poorly understood. Only a few longitudinal follow-up studies have been
      published thus far, and most of them have been based on highly selected groups,
      such as physical education teachers or senior athletes. OBJECTIVE AND METHODS: On
      the basis of random samples of a general population, the purpose of this study
      was to analyze changes in bicycle test performance in two longitudinal designs: a
      10-year follow-up period from 50 to 60 years of age, using a submaximal test
      protocol, and another 10-year follow-up period from 70 to 80 years of age, using
      indirect voluntary maximal tests. In addition, the preventive value of the
      bicycle test results for survival at different age levels was analyzed. The
      subjects in the first part of the study were members of a random sample of
      originally 514 men and 461 women living in the Glostrup area, close to
      Copenhagen, Denmark, in 1964. Of these, 367 men (71.4%) and 206 women (44.7%)
      were tested at the age of 50 years, and 309 men and 245 women were tested 10
      years later. The subjects in the second part of the study came from the same
      original sample. At 70 years of age 171 men and 154 women and at 80 years of age
      70 men and 68 women took part in the maximal test. RESULTS: The submaximal test
      results between the ages of 50 and 60 years showed a mean annual decline in body
      mass adjusted maximal power in sustained work (W/kg) of 0.54% in men and of 0.90%
      in women. Between the ages of 70 and 80 years, when the indirect maximal tests
      were applied, the annual decline in men was on average 1.79% and in women 3.03%.
      When the associations of submaximal test results at ages 50-60 years and the
      voluntary maximal test results at the higher ages were analyzed, a moderate
      positive correlation was observed with the results obtained at the age of 70
      years. The survival analyses showed that the submaximal bicycle test results
      (W/kg body mass) at the age of 60 years had a predictive value for survival in
      women during the subsequent 10-year period. The same was true for the maximal
      test results obtained at the age of 70 years in men; a significantly larger
      proportion of men in the lowest quintile died during the subsequent 10 years than
      of those belonging to the higher quintiles. CONCLUSIONS: The changes in body mass
      related maximal power in sustained work observed in this population on the basis
      of longitudinal studies among the age groups 50-60 and 70-80 years indicated a
      steeper decline at the higher ages. The decline was relatively more pronounced in
      women than in men. However, differences in the test protocols employed at
      different times limit the possibilities for overall comparisons across the data.
      The results of the submaximal bicycle ergometer tests in middle-aged female
      subjects (60 years old) had a predictive value for survival over the 10 years
      immediately following the test; likewise, the voluntary maximal test results at
      higher ages predicted survival in men.

PMID- 11340320
TI  - Slip resistance of casual footwear: implications for falls in older adults.
AB  - BACKGROUND: A large proportion of falls in older people are caused by slipping.
      Previous occupational safety research suggests that inadequate footwear may
      contribute to slipping accidents; however, no studies have assessed the slip
      resistance of casual footwear. OBJECTIVE: To evaluate the slip resistance of
      different types of casual footwear over a range of common household surfaces.
      METHODS: The slip resistance of men's Oxford shoes and women's fashion shoes with
      different heel configurations was determined by measuring the dynamic coefficient
      of friction (DCoF) at heel contact (in both dry and wet conditions) on a bathroom
      tile, concrete, vinyl flooring and a terra cotta tile using a specially-designed
      piezoelectric force plate apparatus. RESULTS: Analysis of variance revealed
      significant shoe, surface, and shoe-surface interaction effects. Men's Oxford
      shoes exhibited higher average DCoF values than the women's fashion shoes,
      however, none of the shoes could be considered safe on wet surfaces. Application
      of a textured sole material did not improve slip resistance of any of the shoes
      on wet surfaces. CONCLUSION: Heel geometry influences the slip resistance of
      casual footwear on common household surfaces. The suboptimal performance of all
      of the test shoes on wet surfaces suggests that a safety standard for casual
      footwear is required to assist in the development of safe footwear for older
      people.

PMID- 11340321
TI  - Changes in antioxidative mechanisms in elderly patients with non-insulin
      dependent diabetes mellitus. Investigation of the redox dynamics of alpha
      tocopherol in erythrocyte membranes.
AB  - BACKGROUND: Recently, it has been suggested that the onset and aggravation of
      diabetes are closely related to free radicals. Also, vitamin E is a lipophilic
      free radical scavenger that is localized mainly in biomembranes. OBJECTIVE: The
      purpose of this study was to clarify the defensive mechanisms against oxidative
      stress by investigating the differences in the redox dynamics of alpha-tocopherol
      in plasma and erythrocyte membranes between elderly patients with non-insulin
      dependent diabetes mellitus (NIDDM) and healthy elderly subjects. METHODS: Total,
      alpha-, beta-, gamma- and delta-tocopherol and alpha-tocopherolquinone
      concentrations were determined by high-performance liquid chromatography with a
      redox detection mode using a series of four coulometric working electrodes.
      RESULTS: The alpha-tocopherolquinone/alpha-tocopherol ratio in plasma and
      erythrocyte membranes was not different between the two groups. Both the alpha
      tocopherol concentrations in erythrocyte membranes and ratio of alpha-tocopherol
      in erythrocyte membranes to alpha- tocopherol in plasma was significantly lower
      in elderly NIDDM patients than in healthy subjects. CONCLUSION: These findings
      suggest that alpha-tocopherol is used normally in both plasma and erythrocyte
      membranes and alpha-tocopherol uptake in erythrocyte membranes is significantly
      decreased in elderly NIDDM patients. The functional disorder of the antioxidative
      activity of alpha-tocopherol in erythrocyte membranes due to impairment of this
      transfer mechanism may be associated with the pathogenesis of NIDDM.

PMID- 11340322
TI  - Lung cancer in the octogenarian.
AB  - BACKGROUND: Older patients with lung cancer tend to have significant coexisting
      diseases and less aggressive treatment is often advisable. OBJECTIVE: To
      investigate the clinicopathological features of lung cancer in patients aged 80
      years and over. METHODS: The medical records of 966 patients with lung cancer
      between 1976 and 1999 were reviewed retrospectively. RESULTS: There were 56
      (5.8%) patients 80 years old or over. Thirty-nine (70%) were male, and 22 (39%)
      patients had poor performance status (2-4). Some of the patients had a medical
      history of cardiovascular disease (n = 23; 41%), cerebrovascular disease (n = 5;
      9%), diabetes mellitus (n = 11; 20%), or malignant disease (n = 8; 14%). Twenty
      one (35%) patients were diagnosed as having surgically resectable disease and 20
      patients underwent radiotherapy, but 25 patients only received supportive care
      because of concomitant illnesses. Only 9 and 2 patients, respectively, had
      chemotherapy and surgery. There was no statistical difference in the survival
      rate of the two groups of patients receiving radiotherapy or supportive care.
      CONCLUSION: Adequate palliative care to provide prolonged quality survival is an
      appropriate primary goal of therapy for lung cancer in the octogenarian until
      less invasive treatments are developed.

PMID- 11340323
TI  - Institutionalized older adults in a health district in the United Arab Emirates:
      health status and utilization rate.
AB  - BACKGROUND: Little is known about the rate of institutionalization and health
      status of nursing home (NH) type patients living in the Middle East. This study
      was set in the Al-Ain Medical District, a geographically discrete region of the
      United Arab Emirates, a country with a developing economy located on the shores
      of the Arabian Gulf. NH-type patients were defined as people aged 60 years and
      older who were admitted to a hospital or a long-term institutionalized setting
      for at least 6 weeks and with no evidence of an expectation of discharge at the
      time of the evaluation. OBJECTIVE: To determine the clinical, functional,
      cognitive, and nutritional status of NH-type patients living in a defined
      community within a developing country. METHOD: Cross-sectional survey. RESULTS:
      All NH-type patients were identified, and all were included in this study (n =
      47, 100% participation rate). All were located within three public institutions,
      none of which was a dedicated NH facility. The rate of institutionalization was
      7.0-14.0 per 1,000 people aged 65 or older. The age distribution was 30% (60-74
      years), 49% (75-84 years), and 21% (85+ years). The length of stay was 3.8 years.
      The female:male ratio was 1.6. All except 1 had a neurological disorder, and 89%
      had dementia. The cognitive deficits were severe with only 61% alert, 41% able to
      speak, 17% orientated in place, and 15% orientated in time. The functional status
      was also poor: 98% received assistance with all instrumental activities of daily
      living, 85% received assistance with five activities of daily living, and 94%
      were bed bound. The nutritional status was also impaired with a mean body weight
      of 45 +/- 14 kg and a mean albumin level of 3.1 +/- 0.6 g/dl. When compared with
      the USA data from the National Center for Health Statistics, the study population
      was younger, had a longer length of stay, a lower female:male ratio, a higher
      rate of neurological diseases and dementia, and were far more dependent and
      disoriented. The rate of institutionalization was one sixth to one third of that
      in the USA. CONCLUSION: From these data we concluded that this region has a
      distinctly different population of institutionalized older people who demonstrate
      greater impairments in all domains of health status.

PMID- 11340324
TI  - Neuroendocrinology of aging: the potential of gene therapy as an interventive
      strategy.
AB  - OBJECTIVE: This paper reviews the current status of gene therapy in the
      neuroendocrine system and discusses the interventive potential of this
      methodology for neuroendocrine pathologies associated with aging. BACKGROUND AND
      RESULTS: A brief description is first presented of the viral-vector-based gene
      delivery systems being currently used in the neuroendocrine system, namely the
      adenoviral and herpetic (HSV1) vector systems. Next, an account of the
      neuroendocrine pathologies for which gene therapy approaches in animal models are
      being implemented is provided. This includes the treatment of experimental
      pituitary tumors by adenoviral-vector-mediated transfer of the suicide gene for
      the HSV-1 thymidine kinase. At the hypothalamic level, an adenovirus harboring
      the cDNA for arginine vasopressin has been used in Brattleboro rats to correct
      their diabetes insipidus. Next, the interventive potential of gene therapy for
      correcting age-associated neurodegenerative processes at neuroendocrine level is
      outlined. Finally, the role that emerging technologies may play in the
      development of future genetic therapies for aging is considered. CONCLUSION:
      Although effective implementation of gene therapy strategies still faces
      significant technical obstacles, these are likely to be progressively overcome as
      gene delivery systems are refined.

PMID- 11340325
TI  - Chemokines, chemokine receptors and allergy.
AB  - Chemokines are a group of cytokines that are responsible for the influx of blood
      cells, including T and B lymphocytes, monocytes, neutrophils, eosinophils and
      basophils, in allergic and other inflammatory conditions. They function as G
      protein-coupled chemotactic factors which also activate the cells with which they
      interact. Certain chemokines function within the afferent arm of the immune
      system, in which antigen is processed and antibody formation initiated, and
      others are active within the effector pathways of cellular immunity and late
      phase allergic reactions. Th2 lymphocytes, which are critical for allergy, employ
      the CC chemokine receptors CCR4 and CCR8 with the ligands thymus- and activation
      regulated chemokine (TARC), macrophage-derived chemokine (MDC) and I-309,
      respectively. The chemokine receptor CCR3 and ligands monocyte chemoattractant
      protein (MCP)-3, MCP-4, regulated upon activation normal T cell expressed and
      secreted (RANTES) and eotaxins I and II are of particular relevance for the
      recruitment and activation of eosinophils. Th1 reactions depend upon interferon
      gamma-induced CXC chemokines interferon- inducible protein (IP)-10, interferon
      inducible T cell-alpha chemoattractant (iTAC) and monokine induced by interferon
      gamma (MiG), which bind to chemokine receptor CXCR3.

PMID- 11340326
TI  - Dendritic cells as regulators of the immune response to inhaled allergen: recent
      findings in animal models of asthma.
AB  - Antigen-presenting dendritic cells are essential for the recognition and
      presentation of allergens to the cells of the immune system. Airway dendritic
      cells capture allergen in the mucosa and present it to naive T cells after
      migration into the draining lymph nodes. In this review article, we discuss the
      most recent findings from animal models of asthma, which highlight an essential
      role for these cells in the induction and maintenance of eosinophilic airway
      inflammation. This increasing knowledge might lead to the identification of new
      targets for the prevention and therapy of asthma.

PMID- 11340327
TI  - New developments in the diagnosis and treatment of hymenoptera venom allergy.
AB  - According to most textbooks, diagnostic tests with Hymenoptera venoms are
      reliable, and immunotherapy with these venoms in Hymenoptera-venom-allergic
      patients leads in near to 100% to full protection. Careful analysis of the
      literature shows however that the specificity of diagnostic tests is far from
      perfect and that both efficacy and tolerance, especially in patients receiving
      honeybee venom immunotherapy, are still suboptimal. The major allergens of
      honeybee and vespid venoms are now available in recombinant form. Preliminary
      trials analyzing diagnostic tests with recombinant allergens in honeybee venom
      allergy are promising: the specificity is clearly increased in both skin testing
      and in determining venom-specific IgE antibodies when compared to natural venom
      allergens. An important recent finding is the frequent association of severe
      Hymenoptera venom allergy and elevated basal serum levels of the mast-cell
      specific enzyme tryptase. Elevated levels are found in up to 30% of the patients
      with a history of severe shock reactions following Hymenoptera stings. The
      current findings indicate that basal tryptase levels indicating an increased mast
      cell load are much more frequent than previously thought and are a risk factor
      for severe or even fatal sting reactions. Premedication with antihistamines in
      the initial phase of venom immunotherapy reduced both local and systemic allergic
      side effects in several controlled studies. In a retrospective analysis of one of
      these trials it was found that reexposure during immunotherapy resulted in
      significantly more systemic allergic reactions in patients on placebo than on
      antihistamine premedication, suggesting that initial antihistamine premedication
      might increase the efficacy of venom immunotherapy. Different ways of allergen
      modification for venom immunotherapy have been proposed. While the results with
      chemical modifications were not convincing, recent studies with T-cell epitope
      peptides from the major bee venom allergen phospholipase A(2) look promising.
      Patient-tailored cocktails of recombinant venom allergens or isoforms thereof may
      be another possibility in the future. A number of prospective studies analyzing
      the duration of venom immunotherapy required for long-term protection have been
      published in the last decade. While most patients are still fully protected 1
      year after discontinuation of therapy, relapses may occur in up to 20% of
      patients reexposed many years after treatment. Various risk factors for such
      relapses have been identified.

PMID- 11340328
TI  - Effects of site-directed mutagenesis in the cysteine residues and the N
      glycosylation motif in recombinant Der f 1 on secretion and protease activity.
AB  - BACKGROUND: The group 1 allergens from mite feces, which belong to the papain
      like cysteine protease family, are the most significant in-door allergens. In
      this study, we analyzed the contribution of the cysteine residues and N
      glycosylation in Der f 1, the group 1 allergen from Dermatophagoides farinae, to
      secretion and maturation by using systems for expression of recombinant Der f 1
      (rDer f 1). METHODS: The rDer f 1 and its mutants were expressed in yeast Pichia
      pastoris and insect SF9 cells. Secretion of their proforms was checked by SDS
      PAGE or immunoblotting. Protease activities of the secreted proform of a mutant
      and the mature form were compared with that of native Der f 1. RESULTS: The
      proform of a mutant Der f 1, pro-N53Q, whose consensus motif for N-glycosylation
      was disrupted, was not secreted in insect SF9 cells although secreted in P.
      pastoris. Indirect evidence was obtained to support the disulfide bond formation
      between Cys4 and Cys118, which were not conserved in papain. A mutant for Cys35
      in the catalytic site of the cysteine protease, pro-C35S/N53Q, was secreted, but
      the other mutants for cysteines concerning intramolecular disulfide bonds were
      not secreted in P. pastoris. The prosequence of pro-C35S/N53Q was removed by an
      in vitro activation process. The mature C35S/N53Q showed low protease activity.
      CONCLUSION: N-glycosylation is essential for secretion in insect SF9 cells but
      not in P. pastoris. Disulfide bonds are essential for secretion in P. pastoris. A
      mutation in the catalytic site, C35S, is not completely critical to removal of
      the prosequence and protease activity. The findings are useful for future design
      of recombinant products for application in immunotherapy.

PMID- 11340329
TI  - The impact of the route and frequency of antigen exposure on the IgE response in
      allergy.
AB  - BACKGROUND: Knowledge of the factors which control IgE production is essential in
      order to understand the pathogenesis of immediate hypersensitivity reactions. We
      have studied the extent to which the route and frequency of antigen application
      as well as different antigen amounts may influence IgE synthesis. METHODS: We
      established sensitisation protocols in BALB/c mice, in which various doses of
      ovalbumin (Ova) were applied via intranasal, epicutaneous or intraperitoneal
      routes. Ova-specific antibodies were measured by ELISA. After 6 weeks of
      sensitisation, anaphylactic shock was measured following intravenous challenge
      with Ova. In addition, bronchoalveolar lavages were performed in intranasally
      sensitised mice. RESULTS: We were able to show that the most efficient IgE
      production was achieved by long-term antigen application via the airways, leading
      to local allergic airway pathology. The epicutaneous route of antigen application
      also induced very high IgE titres, while intraperitoneal sensitisation led to
      significantly lower IgE levels. After intraperitoneal sensitisation, IgE
      synthesis was best induced by increasing the frequency of antigen application,
      but not by increasing the amount of antigen. In all groups of mice, Ova-specific
      IgE antibodies were high enough to induce systemic allergic symptoms leading to
      anaphylactic shock. The severity of shock correlated with the amount of specific
      IgE. CONCLUSIONS: Taken together, our results demonstrate that antigen
      application via the airways or skin induces IgE synthesis more efficiently than
      via the intraperitoneal route. Few exposures with high-dose antigen are less
      efficient than multiple exposures with low doses. Our finding that both the route
      and the frequency of antigen application strongly influence IgE synthesis may
      help to understand how environmental antigens lead to allergic sensitisation.

PMID- 11340330
TI  - Regulation of surface FcepsilonRI expression on human eosinophils by IL-4 and
      IgE.
AB  - BACKGROUND: Recent studies have demonstrated that eosinophils from allergic
      patients express low levels of FcepsilonRI on their surface, but the regulatory
      mechanisms of eosinophil surface FcepsilonRI expression are not fully understood.
      We investigated whether IL-4 and IgE, which are reported to regulate surface
      FcepsilonRI expression on human mast cells, are able to affect surface
      FcepsilonRI expression in normal human eosinophils. METHODS: Eosinophils purified
      from peripheral blood were cultured with IL-5 and with or without IL-4 and/or
      IgE, and surface FcepsilonRI expression was analyzed by flow cytometry using an
      anti-FcepsilonRI mAb, CRA-1. RESULTS: Apparent FcepsilonRI expression
      (approximately 1% of mast cell FcepsilonRI levels) was observed in eosinophils
      cultured with both IL-4 and IgE. A combination of IL-4 (>or=1 ng/ml) and IgE
      (>or= 0.5 microg/ml) was necessary for the maximal induction of surface
      FcepsilonRI expression. In the presence of IL-4 and IgE, eosinophils cultured for
      2 days demonstrated low but statistically significant levels of surface
      FcepsilonRI, which reached a plateau after 7 days of culture. However, cross
      linkage of surface FcepsilonRI molecules by CRA-1 or anti-IgE did not induce any
      eosinophil activation. CONCLUSIONS: IL-4 and IgE can affect the levels of surface
      FcepsilonRI on normal human eosinophils. FcepsilonRI expression on eosinophils
      may be regulated by a mechanism similar to that in mast cells.

PMID- 11340331
TI  - (S)-albuterol increases the production of histamine and IL-4 in mast cells.
AB  - BACKGROUND: Racemic albuterol is an equimolar mixture of (R)-albuterol and (S)
      albuterol. Previous studies indicated that (S)-albuterol may exert
      proinflammatory effects. We investigated the effect of (S)-albuterol in the
      production of mast cell mediators such as histamine and interleukin (IL)-4.
      METHODS: Murine mast cells were either unstimulated or stimulated by IgE-receptor
      crosslinking. Both groups of mast cells were pretreated with either (R)- or (S)
      albuterol. Histamine release and IL-4 secretion were measured by ELISA.
      Expression of L-histidine decarboxylase (L-HDC) and IL-4 was analyzed by
      semiquantitative reverse transcription-polymerase chain reaction. RESULTS: In the
      overnight IgE-stimulated group, secreted histamine and total histamine were
      approximately 19.9 and 18.3% greater in cells co-treated with (S)-albuterol than
      untreated cells, respectively (n = 4, p < 0.002, p < 0.02), whereas there was no
      significant difference between the cells treated with (R)-albuterol and untreated
      cells. When the IgE-stimulated cells were treated with (S)-albuterol for 6 and 24
      h, histamine release was approximately 18.3 and 24% greater, respectively (n = 4,
      p < 0.01). L-HDC is an essential enzyme for synthesizing histamine and its
      message was significantly induced in mast cells treated with (S)-albuterol. Both
      IL-4 message and protein were also significantly increased after treatment with
      (S)-albuterol. In the overnight IgE-stimulated group, IL-4 secretion was
      increased by approximately 58.8% upon exposure to (S)-albuterol (n = 5, p <
      0.01). (R)-albuterol had no effect on mast cell mediator release. CONCLUSION: (S)
      albuterol may have adverse effects in asthma control by activating mast cells to
      produce inflammatory mediators such as histamine and IL-4.

PMID- 11340332
TI  - Roles of CD4+ and CD8+ T cells in adjuvant activity of diesel exhaust particles
      in mice.
AB  - Through an imbalance in Th1 and Th2 cytokine profiles, diesel exhaust particles
      (DEP) are thought to induce Th2-dominated IgE and IgG1 production. However, the
      roles of CD4+ and CD8+ T-cell subtypes in the increased immune responses to
      antigen in mice exposed to DEP are unclear. In the present study, we investigated
      whether treatment with anti-CD4 or anti-CD8 mAb abrogated the adjuvant activity
      of DEP. On day -1 and day 1, each group of mice was injected intraperitoneally
      with anti-CD4, anti-CD8, or rat IgG (vehicle). On day 0, the mice were immunized
      with ovalbumin (OVA) or OVA plus DEP. After 3 weeks, each mouse was boosted with
      10 microg of OVA alone. On day 7 after the first injection with OVA+DEP or OVA
      alone, the numbers of total, IA+, CD80+/IA+ and CD86+/IA+ cells in peritoneal
      exudate cells (PEC) were higher in OVA+DEP-immunized mice than in OVA-immunized
      mice. Depletion of CD8+ cells resulted in a modulation of the production of
      granulocyte-macrophage colony-stimulating factor, IL-12 and PGE(2) in peritoneal
      exudate fluid from OVA+DEP-immunized mice. On day 28, DEP injection markedly
      increased IL-4 production in the culture supernatants of spleen cells from CD4+
      or CD8+-depleted mice. Depletion of CD8+ cells in OVA+DEP-immunized mice resulted
      in a decrease in IFN-gamma production compared with that in OVA-immunized mice.
      Adjuvant activity of DEP was observed in anti-OVA IgE, anti-OVA IgG1, anti-OVA
      IgG3, and total IgE production. Depletion of CD4+ T cells abrogated the adjuvant
      effect of DEP on anti-OVA IgE, and anti-OVA IgG1 production in plasma. However,
      depletion of CD8+ T cell inhibited the upregulated anti-OVA IgG3 production.
      These findings suggest that DEP injection may affect not only the function of
      CD4+ cells but also that of CD8+ T-cell subsets to modulate the synthesis of
      proinflammatory cytokine in PEC and type-1 and type-2 cytokine production in
      spleens.

PMID- 11340333
TI  - CD4+IL13+ T lymphocytes at birth and the development of wheezing and/or asthma
      during the 1st year of life.
AB  - BACKGROUND: Despite our knowledge that maternal inheritance influences the
      development of asthma in childhood, attempts to identify a clear-cut Th2-oriented
      cytokine production by T lymphocytes at birth have given conflicting results. The
      prognostic significance of these cells for asthma development later in life
      remains to be determined. METHODS: We evaluated at the single cell level Th1- and
      Th2-type cytokines in 208 randomly selected cord blood mononuclear cell (CBMC)
      samples obtained from pregnant women (group A, n = 68 with diagnosed respiratory
      allergic disease; group B, n = 140, with no evidence of atopy), and prospectively
      followed newborns for 1 year. RESULTS: There was no difference in IFN-gamma, IL-4
      and IL-5 production at birth between both groups, whereas a correlation between
      CD4+IL13+ lymphocytes from CBMC samples derived from atopic mothers and the
      occurrence of wheezing and/or asthma during the 1st year of life was found.
      CONCLUSIONS: Our observations suggest that the intracellular cytokine profile of
      cord blood CD4+ cells, in terms of IL-13 production, could be considered a useful
      tool for a more accurate identification of newborns from atopic mothers who are
      at high risk of developing asthma.

PMID- 11340334
TI  - Baker's asthma due to xylanase and cellulase without sensitization to alpha
      amylase and only weak sensitization to flour.
AB  - BACKGROUND: The baking additives xylanase and cellulase were described as baking
      additives causing baker's asthma. It is not known whether monosensitization to
      these enzymes may occur. METHODS: We present a case report of a baker with work
      related asthma evaluated by skin prick test (SPT), enzyme-linked immunosorbent
      assay (EAST), immunoblot, EAST and immunoblot inhibition, and specific bronchial
      challenge. Fungal xylanase and alpha-amylase were measured by two-site enzyme
      immunoassays in products used by the patient at work. RESULTS: Allergy to
      xylanase and cellulase was demonstrated by SPT, EAST, immunoblot and specific
      bronchial challenge (for xylanase only). No sensitization to alpha-amylase could
      be demonstrated, but there was a weak flour allergy as documented by EAST and
      immunoblot and a positive occupational-type challenge with high concentrations of
      rye flour. Four baking additives contained measurable amounts of fungal alpha
      amylase and xylanase, without a correlation between these enzymes. CONCLUSIONS:
      We conclude that occupational asthma due to the baking additives xylanase and
      cellulase may occur without concomitant sensitization to alpha-amylase and only
      weak sensitization to flour.

PMID- 11340335
TI  - Leptin receptor immunoreactivity is present in ascending serotonergic and
      catecholaminergic neurons of the rat.
AB  - Using double-labelling immunohistochemistry we have studied the localisation of
      leptin receptor proteins including both long and short forms and their possible
      presence in serotonergic (5-HT) and catecholaminergic neurons in the rat brain.
      Leptin receptor immunoreactivity was found to be widely distributed in the
      central nervous system including cortical areas, amygdala, several hypothalamic
      and thalamic nuclei, the raphe system, pontine nuclei, locus coeruleus,
      parabrachial nucleus, tractus solitarus and the medullary reticular formation.
      Serotonergic cell groups were identified by 5-HT immunocytochemistry and
      classified according to standard nomenclature. High degrees of co-existence of
      leptin receptor immunoreactivity with serotonin in the raphe system were observed
      in B1, B5, B6, B7, B8 and B9. In B3 and B2 less than 50% of the 5-HT cells
      colocalised leptin receptor immunoreactivity. Brainstem and diencephalic
      (catecholaminergic) neurons were identified by tyrosine hydroxylase
      immunocytochemistry and classified according to standard nomenclature. Within the
      periventricular hypothalamic dopaminergic nuclei A14 and A12, the metencephalic
      noradrenergic A6, A7, A2, A1, and the adrenergic C3, C2 and C1 cell groups,
      nearly all tyrosine hydroxylase-positive cells colocalised with leptin receptor
      immunoreactivity. In contrast, co-existence of tyrosine hydroxylase and leptin
      receptor immunoreactivities in the dopaminergic A13, A11, A10, A9 and A8 cell was
      practically non-existent. Thus leptin, the adipose tissue-derived ligand of the
      leptin receptor, may in some brain areas directly influence serotonergic,
      dopaminergic, adrenergic and noradrenergic inputs to the periventricular and
      medial hypothalamic nuclei.

PMID- 11340336
TI  - Effects of leptin and corticosterone on the expression of corticotropin-releasing
      hormone, agouti-related protein, and proopiomelanocortin in the brain of ob/ob
      mouse.
AB  - The present study was conducted to assess the effect of leptin and corticosterone
      on the expression of corticotropin-releasing hormone (CRH), proopiomelanocortin
      (POMC) and agouti-related protein (AGRP) in the mouse brain. To this end, a 3 x 3
      factorial experiment was designed in which adrenalectomized (ADX) ob/ob mice were
      treated with leptin and corticosterone. Leptin and corticosterone downregulated
      CRH expression in the paraventricular hypothalamic nucleus (PVH). Leptin
      prevented the stimulating effects of ADX on the expression of CRH and the
      combination of small doses of leptin and corticosterone was as potent as the high
      dose of corticosterone in suppressing CRH mRNA expression in the PVH. Leptin and
      corticosterone enhanced the expression of CRH in the central nucleus of amygdala
      and in the bed nucleus of the stria terminalis. In addition, the present results
      confirmed the downregulating effects of leptin on the expression of AGRP mRNA in
      the hypothalamic arcuate nucleus (ARC), and demonstrated that this effect was
      more apparent in ADX mice treated with corticosterone than in ADX mice not
      supplemented with corticosterone. Also, leptin and corticosterone had opposite
      effects on the expression of POMC in the ARC. The opposite effect of leptin and
      corticosterone on the expression of POMC and AGRP seems consistent with the
      reported effects that these hormones and peptides have on food intake and
      thermogenesis, suggesting that the modulation of POMC and AGRP expression can be
      a mechanism whereby leptin and corticosterone exert their effects in the
      regulation of energy balance. In contrast, the similarity in the action of leptin
      and corticosterone is not a priori consistent with a role of CRH in the effects
      of these hormones in the regulation of energy balance. The downregulating effect
      of leptin on the expression of CRH in the PVH strongly suggests that leptin can
      be a potent regulator of hypothalamic-pituitary-adrenal axis activity. Finally,
      the present results suggest that the effects of leptin on the expression of CRH,
      POMC and AGRP are not curbed by glucocorticoids.

PMID- 11340337
TI  - Glucose and insulin increase the transport of leptin through the blood-brain
      barrier in normal mice but not in streptozotocin-diabetic mice.
AB  - Since fasting is one of the few factors found to change the rate of entry of
      leptin into brain, we used multiple-time regression analysis to study the effects
      of pretreatment with glucose or insulin on leptin transport across the blood
      brain barrier (BBB). Two hours after intraperitoneal injection of glucose (3
      g/kg), there was a statistically significant increase in the entry rate (K(i)) of
      leptin in fasted (from 4.91 +/- 0.70 x 10(-4) ml/g x min to 9.03 +/- 1.00 x 10(
      4) ml/g x min) but not (p = 0.15) in nonfasted normal (from 4.90 +/- 1.21 x 10(
      4) ml/g x min to 6.42 +/- 1.79 x 10(-4) ml/g x min) or fasted streptozotocin
      (STZ)-treated diabetic mice (from 4.043 +/- 0.959 x 10(-4) ml/g min to 5.395 +/-
      1.355 x 10(-4) ml/g min). Insulin (10 U/kg) increased leptin influx in fasted
      (from 4.77 +/- 0.26 x 10(-4) ml/g x min to 10.6 +/- 0.15 x 10(-4) ml/g x min at
      0.5 h) and nonfasted (from 4.64 +/- 0.75 x 10(-4) ml/g x min to 7.46 +/- 1.48 x
      10(-4) ml/g x min at 0.5 h) normal mice, but not in STZ-diabetic mice deficient
      in insulin (and leptin), even though basal concentrations of glucose were
      similarly increased in the nonfasted normal and STZ-treated mice. Moreover, the
      basal rate of leptin influx was the same in overnight fasted normal mice,
      nonfasted normal mice and STZ-diabetic mice. The results indicate that glucose
      and insulin can increase leptin transport, but they probably are not the
      principal factors responsible for the regulatory effect of the BBB on leptin
      entry into the brain.

PMID- 11340338
TI  - Low leptin levels but normal body mass indices in patients with depression or
      schizophrenia.
AB  - Appetite, food intake and weight are frequently altered in psychiatric disorders
      such as major depression and schizophrenia. The few studies investigating weight
      and the body mass index (BMI) have yielded variable results. Leptin, a fat cell
      derived hormone signalling to the brain the size of the adipose tissue, plays a
      pivotal role in the regulation of weight and food intake. Moreover, leptin is
      involved in the control of other behaviors and in brain development. There is
      almost no information about the amounts of circulating leptin in major depression
      or schizophrenia. We investigated the BMI and plasma leptin levels in patients
      with major depression (n = 62), schizophrenia (n = 42), and in healthy controls
      (n = 64). Mean BMIs did not differ between groups. However, leptin levels were
      significantly lower in both patient groups compared to healthy controls.
      Moreover, patients suffering from schizophrenia showed significantly lower leptin
      levels than depressed patients. Decreased leptin levels were independent of
      psychotropic medication. We conclude that depression and schizophrenia go along
      with decreased systemic leptin concentrations that cannot be explained by
      medication or an altered BMI. Hence, leptin might play an important
      pathophysiological role in these psychiatric disorders that deserves further
      scientific attention.

PMID- 11340339
TI  - Appetite-suppressing effects of urotensin I and corticotropin-releasing hormone
      in goldfish (Carassius auratus).
AB  - Fish urotensin I (UI), a member of the corticotropin-releasing hormone (CRH)
      family of peptides, is a potent inhibitor of food intake in mammals, yet the role
      of UI in the control of food intake in fish is not known. Therefore, to determine
      the acute effects of UI on appetite relative to those of CRH, goldfish were given
      intracerebroventricular (i.c.v.) injections of carp/goldfish UI and rat/human CRH
      (0.2-200 ng/g) and food intake was assessed for a 2-hour period after the
      injection. UI and CRH both suppressed food intake in a dose-related manner and UI
      (ED50 = 3.8 ng/g) was significantly more potent than CRH (ED50 = 43.1 ng/g).
      Pretreatment with the CRH receptor antagonist, alpha-helical CRH(9-41), reversed
      the reduction in food intake induced by i.c.v. UI and CRH. To assess whether
      endogenous UI and CRH modulate fish appetite, goldfish were given intraperitoneal
      implants of the glucocorticoid receptor antagonist, RU-486 (50 and 100 microg/g),
      or the cortisol synthesis inhibitor, metyrapone (100 and 200 microg/g), and food
      intake was monitored over the following 72 h. Fish treated with either RU-486 or
      metyrapone were characterized by a sustained and dose-dependent reduction in food
      intake. Pretreatment with i.c.v. implants of alpha-helical CRH(9-41) partially
      reversed the appetite-suppressing effects of RU-486 and metyrapone. In a parallel
      experiment, the effects of RU-486 (100 microg/g) and metyrapone (200 microg/g)
      intraperitoneal implants on brain UI and CRH gene expression were assessed.
      Relative to sham-implanted controls, fish treated with RU-486 or metyrapone had
      elevated UI mRNA levels in the hypothalamus and CRH mRNA levels in the
      telencephalon-preoptic brain region. Together, these results suggest that UI is a
      potent anorectic peptide in the brain of goldfish and that endogenous CRH-related
      peptides can play a physiological role in the control of fish appetite.

PMID- 11340340
TI  - Glucocorticoid and mineralocorticoid receptors are involved in the facilitation
      of anxiety-like response induced by restraint.
AB  - In previous studies, we have shown that male Wistar rats exposed to a single
      inescapable stressor session (15 min restraint) exhibited 24 h later an
      anxiogenic-like behavior in the elevated plus-maze (EPM), which was reversed by
      inhibition of corticosterone (CS) synthesis with metyrapone (75 mg/kg i.p.) 3 h
      before stress. Since CS binds to two central corticosteroid receptors, the
      mineralocorticoid (MR) and the glucocorticoid (GR) receptors, involvement of MR
      and GR in the modulation of anxiogenic responses was assessed in the EPM.
      Administration of the GR agonist dexamethasone (Dex, 1.25 microg/kg s.c.) to
      metyrapone-pretreated rats 1 h before restraint restored the anxiogenic-like
      response induced by the stressor. Removal of the adrenals also inhibited the
      anxiogenic-like effect, which was restored by either Dex (1.25 microg/kg s.c.),
      the MR agonist deoxycorticosterone (0.8 mg/kg s.c.) or CS, the common endogenous
      agonist of MR and GR (5 mg/kg s.c.) administered 1 h before stress.
      Intracerebroventricular infusion to intact animals 15 min before restraint of
      either a selective GR antagonist (A-GR, RU 38486, 100 ng/2 microl), a selective
      MR antagonist (A-MR, RU 28318, 100 ng/2 microl) or a combination of A-GR and A-MR
      (100 ng of each one/2 microl), abolished the stress-induced anxiogenic-like
      effect. The present findings indicate that both MR and GR are involved in the
      long-term CS modulation of the anxiety response induced by restraint. Both
      receptors mediate CS effects in an independent manner.

PMID- 11340341
TI  - Rat strains that differ in corticotropin-releasing hormone production exhibit
      different sleep-wake responses to interleukin 1.
AB  - Corticotropin-releasing hormone (CRH) is a mediator of responses to a variety of
      stressors, including immune challenge. CRH and the hypothalamic-pituitary-adrenal
      (HPA) axis constitute a negative feedback mechanism for actions of
      immunomodulators, such as interleukin (IL) 1. CRH is a potent inducer of waking,
      whereas IL-1 induces slow-wave sleep (SWS). We hypothesize that the complex
      changes in sleep-wake behavior during immune challenge are mediated in part by
      CRH and its antagonism of IL-1-induced enhancement of SWS. To further explore
      this hypothesis, we administered IL-1beta intracerebroventricularly into rats of
      genetically related strains that differ in CRH/HPA axis responsiveness to IL-1
      and determined subsequent alterations in their sleep-wake behavior. Sprague
      Dawley rats responded to central administration of IL-1 with alterations in sleep
      wake behavior as previously reported; SWS increased, and rapid eye movement sleep
      (REMS) and waking decreased. CRH and the HPA axis of Lewis rats are reported to
      be hyporesponsive to challenge; the onset of the IL-1-induced increase in SWS was
      quicker and the peak magnitude of the response greater than in Sprague-Dawley
      rats. In contrast, Fischer 344 rats exhibit greater CRH release and HPA axis
      activation in response to IL-1. IL-1 induced a profound and transient increase in
      waking of Fischer 344 rats before SWS increased. The febrile responses to IL-1 of
      Fischer 344 and Lewis rats were identical and of greater magnitude than those
      observed in Sprague-Dawley rats. Pretreatment with the CRH receptor antagonist
      alpha-helical CRH(9-41) blocked the initial IL-1-induced increase in waking of
      Fischer 344 rats. CRH receptor blockade did not affect the IL-1-induced
      alterations in sleep-wake behavior of Lewis or Sprague-Dawley rats or brain
      temperature of any rat strain. These observations support the hypothesis that CRH
      is both a modulator of responses to IL-1 and is involved in the regulation of
      waking.

PMID- 11340342
TI  - Oral testosterone self-administration in male hamsters.
AB  - The addiction potential of anabolic steroids remains largely unexplored. Here, we
      demonstrate voluntary oral testosterone intake in hamsters. Using a 2-bottle
      choice test, males preferred an aqueous solution of 200 microg/ml testosterone
      over vehicle. However, the taste of testosterone is not highly preferred.
      Addition of testosterone at 400 microg/ml increased fluid consumption from the
      nonpreferred bottle in a 2-bottle choice test, but cholesterol at the same
      concentration reduced drinking, suggesting that testosterone reward is not common
      to all sterols. With food-induced drinking, testosterone maintained fluid intake
      when food was withdrawn. These data demonstrate that oral self-administration of
      testosterone is reinforcing in hamsters, suggesting the potential for dependence
      in human users.

PMID- 11340343
TI  - Evidence that adequacy of dialysis modulates uremic anemia.

PMID- 11340344
TI  - Pathogenesis of focal glomerulosclerosis.
AB  - Focal segmental glomerulosclerosis (FSGS) is the histologic expression of diverse
      processes affecting the renal glomeruli and occurring in primary and secondary
      forms. A number of pathogenic factors have been identified in primary FSGS, and
      multiple etiologies have been defined as contributing factors for the development
      of secondary FSGS. There is a complex interplay between etiologic and pathogenic
      factors, progression factors and intervention in the phenotypic expression of
      FSGS. Key components include genetic predisposition, environmental influences and
      the impact on phenotype of pharmacologic intervention. The phenotypic spectrum
      for FSGS ranges from mild proteinuria and slow progression to a devastating
      clinical syndrome characterized by heavy proteinuria and rapid loss of renal
      function over a period of months. While the pathogenesis is unknown, much is
      known about factors which are involved in the development and progression of both
      primary and secondary FSGS. The ultimate goal of understanding pathogenesis is to
      provide specific nontoxic therapy for those patients who have a definable form of
      FSGS. While this goal is not yet in sight, many types of intervention, not
      addressed in the current chapter, can influence the course of various diseases
      presenting as FSGS. Until specific therapy can be fashioned, it is necessary for
      the clinician caring for these patients to appreciate the complex interaction of
      pathogenetic factors involved in the development and pregression of FSGS, as a
      rationale for providing intervention to prevent development of the disease and to
      slow its course.

PMID- 11340345
TI  - Shiga toxin-1 regulation of cytokine production by human glomerular epithelial
      cells.
AB  - BACKGROUND/AIMS: Inflammatory cytokines may enhance renal injury in post
      diarrheal hemolytic uremic syndrome (Stx HUS) by enhancing the cytotoxic effect
      of Shiga toxins (Stx). The sources of inflammatory cytokines in Stx HUS are
      unclear. Since Stx-1 potently inhibits protein synthesis by glomerular epithelial
      cells (GEC) and increases cytokine release by renal epithelial cells, we examined
      Stx-1 regulation of cytokine production by human GEC. METHODS: Stx-1 (and
      cycloheximide (CHX), another protein synthesis inhibitor) cytotoxicity, protein
      synthesis inhibition, and effect on interleukin-1 (IL-1), interleukin-6 (IL-6),
      and tumor necrosis factor (TNF) release and mRNA levels were determined. RESULTS:
      Stx-1 alone had a modest stimulatory effect on inflammatory cytokine production
      by GEC that occurred at toxin concentrations ranging from minimal to 50%
      inhibition of protein synthesis. CHX, at concentrations that produced similar
      inhibition of protein synthesis, increased IL-1, IL-6, and TNF protein release
      and mRNA accumulation, but in a different time- and dose-dependent pattern than
      Stx. Lipopolysaccharide (LPS) did not change IL-1, but stimulated IL-6 and TNF
      production. LPS and Stx-1 combined stimulated production of all three cytokines
      to a greater extent than either toxin alone. CONCLUSION: These data indicate
      that: (1) Stx-1 alone modestly stimulates GEC inflammatory cytokine production;
      (2) LPS and Stx-1 combined can potently enhance GEC cytokine release, and (3)
      this action of Stx-1 may relate in part to inhibition of protein synthesis but
      cannot be fully attributed to this effect.

PMID- 11340346
TI  - Enhanced expression of plasminogen activator inhibitor 1 in patients with
      nephrotic syndrome.
AB  - Hypercoagulability is present in patients with nephrotic syndrome. However,
      alterations in coagulation and fibrinolysis reflected in the glomeruli and urine
      are not fully understood. We examined plasma and urine concentrations of tissue
      type plasminogen activator (tPA) and type 1 plasminogen activator inhibitor (PAI
      1) in 33 patients with nephrotic syndrome (nephrotic group). We compared these
      concentrations with the concentrations in 30 nonnephrotic patients with chronic
      glomerulonephritis (nonnephrotic group) and with the concentrations in 30 healthy
      volunteers (control group). We also examined fibrin/fibrinogen degradation
      products in serum and urine and plasma D-dimers. The expression of tPA and PAI-1
      was examined in isolated glomeruli using RT-PCR methods. Deposition of
      fibrinogen/fibrin-related antigen was observed by direct immunofluorescence. The
      incidence of fibrinogen/fibrin-related antigen deposition in the nephrotic group
      was significantly higher than that in the nonnephrotic group. The concentrations
      of fibrin/fibrinogen degradation products in serum and urine and of plasma D
      dimers were significantly elevated in the nephrotic group as compared with the
      nonnephrotic and control groups. The plasma concentrations of tPA in the
      nephrotic group were significantly higher than those in the control group. The
      urinary excretion of tPA in the nephrotic group was also significantly higher
      than in the nonnephrotic and control groups. The urinary excretion of PAI-1 in
      the nephrotic group was higher than that in the control group. The ratio of PAI-1
      mRNA to tPA mRNA in glomeruli was increased in the nephrotic group as compared
      with the nonnephrotic group. These results indicate that the fibrinolytic
      activity is increased in patients with nephrotic syndrome despite urinary losses
      of tPA. However, a relatively enhanced expression of PAI-1 may be involved in the
      intraglomerular fibrinogen/fibrin-related antigen deposition seen in nephrotic
      syndrome.

PMID- 11340347
TI  - Carboxymethyllysine in dermal tissues of diabetic and nondiabetic patients with
      chronic renal failure: relevance to glycoxidation damage.
AB  - Carboxymethyllysine (CML) is currently recognized as a major advanced glycation
      end product and a marker for glycoxidation. Plasma CML levels are increased in
      patients with chronic renal failure (CRF). However, significance and mechanism of
      CML accumulation in these patients are poorly understood. The objective of the
      present study was to analyze CML in soluble and collagen-binding fractions of the
      dermis to investigate CML deposition and formation and collagen damage related to
      CML accumulation in patients with CRF. Skin samples (among them autopsy samples)
      were obtained from 33 subjects: 8 nondiabetic CRF patients, 7 diabetic
      predialysis patients with CRF (CRF-DM), 7 hemodialysis patients, and 11 control
      subjects without either CRF or DM. The dermal samples were extracted sequentially
      by phosphate-buffered normal saline, pepsin, and collagenase. The extracts were
      referred to as the soluble fraction and the proteinase-extracted fraction
      (including pepsin-extracted and collagenase-extracted fractions). Our ELISA assay
      for CML in dermal collagen from predialysis patients with CRF (CRF and CRF-DM
      groups) demonstrated that the levels of CML in both the soluble fraction
      (containing soluble CML which was mainly determined by serum clearance) and the
      structural collagen-binding proteinase-extracted fraction (in which high CML
      levels could be a strong indication of in situ formation) were increased and
      could not be completely reduced after hemodialysis in CRF-DM and CRF groups.
      These results suggest that accumulation of CML may be due to both a low serum
      clearance and/or increased in situ CML formation in CRF. CML contents in the
      proteinase extracted fraction inversely correlated with the susceptibility of
      collagen to extraction by proteinases (n = 33, r = -0.59, p < 0.001). Our results
      provide the first biochemical evidence that CML level is increased in both the
      soluble and collagen-binding fractions and that increased CML level resulted in
      increased fractions of proteinase-resistant collagen in dermal extracts of
      patients with CRF.

PMID- 11340348
TI  - Role of radio-guided surgery in recurrent secondary hyperparathyroidism.
AB  - BACKGROUND: The aim of this paper is to state the role of radio-guided surgery
      (RGS) in case of recurrent secondary hyperparathyroidism. METHODS: Two cases of
      recurrent secondary hyperparathyroidism were treated using RGS. After a
      preoperative assessment, which included ultrasonography (US), MRI and (99m)Tc
      radiolabelled sestamibi scan, a radio-guided neck re-exploration was planned. On
      the day of surgery the patients underwent a radionuclide injection. After 90 min,
      surgery began. RESULTS: Dissection was guided by placing the probe in the wound
      to localize any increased concentration of radioactivity. In the first case the
      probe identified the gland located deeply in the right tracheo-esophageal groove;
      in the other case the probe detected a site of increased uptake in the upper
      mediastinum. Both lesions were dissected and excised; a frozen section confirmed
      they were parathyroid glands with diffuse hyperplasia. The operative time was
      less than 60 min in both cases. The patients were discharged on the first
      postoperative day. A decrease in serum calcium and PTH was observed subsequently.
      A minimum follow-up of 6 months did not show any recurrence. CONCLUSION: RGS can
      help in detecting the parathyroid tissue in selected cases of renal
      hyperparathyroidism and makes operation much easier and more predictable.

PMID- 11340349
TI  - An intron 4 gene polymorphism in endothelial cell nitric oxide synthase might
      modulate lipid metabolism in nondiabetic patients on hemodialysis.
AB  - We investigated the relationship between endothelial constitutive nitric oxide
      synthase (ecNOS) gene polymorphism and lipid metabolism in patients with
      nondiabetic chronic renal failure on hemodialysis. Serum from 181 nondiabetic
      patients on hemodialysis were examined. A genomic DNA fragment was amplified by
      polymerase chain reaction (PCR) for determining the ecNOS genotype. The PCR
      products were designated as a and b alleles by electrophoresis. In hemodialysis
      patients, the frequency of the ecNOS4 for b/b, b/a and a/a genotype was 76.6,
      22.8 and 0.6%, respectively. There was not significant difference in the levels
      of total cholesterol (TC), triglyceride (TG) and calculated low-density
      lipoprotein cholesterol (LDL-c) in sera between patients (aa and ba) with the a
      allele and patients (bb) without the a allele. On the other hand, the levels of
      serum high-density lipoprotein cholesterol (HDL-c) in patients with the a allele
      (51.9 +/- 3.33 mg/dl) were significantly higher than those in patients without
      the a allele (43.05 +/- 1.40 mg/dl) (p = 0.005). The frequency of patients with
      the a allele and low levels of serum HDL-c among patients with a long duration of
      dialysis (> or =10 years) was significantly lower than that in patients with
      short duration of dialysis (<10 years) (p = 0.05). It appears that an intron 4
      gene polymorphism in ecNOS may modulate lipid metabolism in nondiabetic patients
      on hemodialysis and the a allele of ecNOS gene polymorphism may affect the
      prognosis of hemodialysis patients with low levels of serum HDL-c.

PMID- 11340350
TI  - Onset, time course, and persistence of increased haemodialysis-induced breath
      isoprene emission.
AB  - Recent findings of increased isoprene emission in the exhaled breath of patients
      undergoing haemodialysis and experimental evidence of the potential toxic and
      cancerogenic effects of isoprene hydrocarbon led us to assess how long
      haemodialysis patients are exposed to how much isoprene after a single
      haemodialysis session. Patients with end-stage renal failure on regular 4-hour
      (from 08.00 to 12.00 h) maintenance haemodialysis three times weekly were
      monitored. The breath isoprene content was analyzed by gas chromatography.
      Intrapatient evaluations were performed by collecting samples before, during, and
      immediately after the haemodialysis session, during the following hours, and on
      the following nondialysis day. The breath isoprene content increased in all
      patients. Isoprene overproduction showing a biphasic pattern was first detected
      soon after the dialysis session ended. These data show that haemodialyzed
      patients seem to be consistently exposed to high endogenous isoprene
      concentrations. The mechanisms and implications of this endogenous isoprene
      overproduction need to be elucidated with regard to the mevalonic pathway and in
      the physiopathological setting of the uraemia-dialysis syndrome.

PMID- 11340351
TI  - Twelve weeks of exercise training increases muscle function and walking capacity
      in elderly predialysis patients and healthy subjects.
AB  - Muscle function declines with age and progressive uraemia. We examined whether
      elderly predialysis patients could improve thigh muscle function, walking
      capacity, and functional mobility to the same extent as elderly healthy subjects
      when participating in 12 weeks of individual muscle endurance exercises for the
      thigh as well as in a low-intensive group programme. The uraemic exercise and
      comparison groups comprised 16 patients (age 76 +/- 7 years, glomerular
      filtration rate 18 +/- 5 ml/min) and 9 patients (age 72 +/- 6 years, glomerular
      filtration rate 16 +/- 5 ml/min), respectively. The healthy exercise and
      comparison groups comprised 18 subjects (age 75 +/- 7 years) and 5 subjects (age
      79 +/- 4 years), respectively. Muscular strength, dynamic endurance, walking
      capacity, and functional mobility increased significantly in both the uraemic and
      the healthy exercise groups after 12 weeks of regular muscle endurance exercise
      training, whereas there was no significant change in static muscle endurance and
      quality of life in either group. None of the values changed for the uraemic
      comparison group nor the healthy comparison group during the observation period.
      Elderly predialysis patients had lower muscle function and mobility as compared
      with elderly healthy subjects, but were able to improve both after 12 weeks of
      exercise training to the same extent as elderly healthy subjects.

PMID- 11340352
TI  - Thy1 glomerulonephritis induced in young lewis rats accelerates age-related
      glomerulosclerosis.
AB  - Age-related and disease-induced glomerulosclerosis (GS) in rats have both been
      well defined in a number of strains and experimental models, but the inter
      relationship between the two is not clear. The present study was undertaken to
      compare the pattern of glomerular injury in these two types of GS. One- and two
      shot Thy1 glomerulonephritis (GN) was induced at 2 months of age and followed for
      12 months. At 12 months histological injury in proteinuric rats was characterized
      by segmental hyaline lesions. Two-shot Thy1 GN resulted in accelerated, but
      morphologically identical injury at 8 months. Histological lesions predictive of
      subsequent accelerated GS were evaluated at 1, 2, 4 and 6 months. In this regard,
      glomerular hypercellularity, rather than hypertrophy or matrix increase, was the
      most consistent histological index of later accelerated disease. The profibrotic
      cytokines transforming growth factor (TGF)-beta(1) and -beta(3) were localized
      distinctly to segmental hyaline lesions, but not to areas of matrix increase
      within the glomerular tuft. This study reveals that GS after Thy1 GN represents
      acceleration of an age-related disease, presents evidence for use of prolonged
      glomerular hypercellularity as the best histological index of future disease
      progression, and correlates the key lesion of GS in these animals, the segmental
      hyaline lesion, with the presence of TGF-beta peptides.

PMID- 11340353
TI  - Nucleotide sequence and expression of rat beta-defensin-1: its significance in
      diabetic rodent models.
AB  - beta-Defensins are epithelium-derived antimicrobial peptides that function in the
      host's innate defense. We identified the first member of the rat beta-defensin
      family, beta-defensin-1 (BD-1), in the kidney and determined its nucleotide
      sequence. It was predicted to be a 37-amino-acid peptide. Rat BD-1 mRNA was
      expressed most abundantly in the kidney, next in skin, tongue, esophagus, and
      uterus, followed (at low levels) by brain, trachea, stomach, urinary bladder, and
      ovary. BD-1 gene expression in rat kidney was not increased by lipopolysaccharide
      administration. BD-1 gene expressions in the kidneys of diabetic rodent models,
      cholecystokinin-insensitive Otsuka Long-Evans Tokushima Fatty rats, leptin
      insensitive obese (fa/fa) Wistar rats, and db/db mice, were significantly lower
      than those of their lean littermates. BD-1 reduction may be in part responsible
      for the high incidence of urinary tract infections in diabetes mellitus.

PMID- 11340354
TI  - Control of the epidermal growth factor receptor and its ligands during renal
      injury.
AB  - AIM: We studied control of the epidermal growth factor (EGF) receptor and its
      ligands during kidney injury, since they may be importantly involved in repair.
      METHODS: The folic acid model of renal injury was used in these studies.
      Messenger RNA (mRNA) was evaluated by solution hybridization.
      Immunohistochemistry of transforming growth factor alpha (TGF-alpha) was also
      performed. RESULTS: Twenty-four hours after folic acid induced acute renal
      injury, creatinine increased from 0.3 +/- 0.03 mg/dl in controls to 2.0 +/- 0.8
      mg/dl in folic acid injured kidneys (n = 4, p < 0.03). mRNA for the EGF receptor
      was increased nearly sevenfold by 24 h, and mRNA for the receptor was increased
      as early as 1 h following folic acid treatment. EGF receptor ligand caused a
      profound downregulation of the receptors in proximal tubule basolateral
      membranes, but receptors returned rapidly to the membrane surface in injured
      kidneys. The mRNA levels for heparin-binding EGF and TGF-alpha, two EGF receptor
      ligands, increased within 1 h of injury. TGF-alpha mRNA increased from 1.0 +/-
      0.09 (relative densitometry units) in control animals to 2.9 +/- 0.13 in folic
      acid treated rats at 24 h (n = 4, p < 0.01), and immunohistochemical staining for
      TGF-alpha increased in injured kidneys at distal nephron sites. CONCLUSIONS:
      These studies indicate that upregulation of the EGF receptor is related to an
      increase in mRNA. The rapid return of receptors to the membrane surface following
      ligand stimulation may be useful in maintaining a mitogenic stimulus. Multiple
      EGF-like ligands may be important in activating the upregulated EGF receptor
      during repair from renal injury.

PMID- 11340355
TI  - Effect of dilazep dihydrochloride on urinary albumin excretion in patients with
      autosomal dominant polycystic kidney disease.
AB  - Proteinuria and microalbuminuria occur with a highly variable severity and are
      associated with progression of autosomal dominant polycystic kidney disease
      (ADPKD). Dilazep dihydrochloride, an antiplatelet drug, is effective in patients
      with immunoglobulin A nephropathy or diabetic nephropathy. We studied whether
      dilazep dihydrochloride affects the urinary albumin excretion (UAE) in
      normotensive and hypertensive patients with ADPKD. Twelve normotensive ADPKD
      patients with microalbuminuria were randomly assigned to two groups: a dilazep
      (300 mg/day) treatment group (n = 6, group A) and a placebo group (n = 6, group
      B). In addition, 10 hypertensive ADPKD patients with microalbuminuria were
      randomly assigned to two groups: a dilazep (300 mg/day) treatment group (n = 5,
      group C) and a placebo group (n = 5, group D). Treatment with dilazep was
      continued for a period of 6 months, at the end of which the UAE was reduced form
      130 +/- 52 to 46 +/- 26 microg/min (p < 0.01) in group A. There was no reduction
      in group C. There were no changes in UAE in placebo groups B and D. These results
      suggest that dilazep dihydrochloride may be effective in reducing UAE in
      normotensive ADPKD patients with microalbuminuria.

PMID- 11340356
TI  - Hereditary hypophosphatemic rickets with hypercalciuria: report of a new kindred.
AB  - We report a new kindred of hereditary hypophosphatemic rickets with
      hypercalciuria. The symptomatic child and several relatives had increased renal
      phosphate clearance leading to hypophosphatemia, hyperabsorptive hypercalciuria,
      low PTH and increased 1,25-(OH)2D serum level. However, association with vitamin
      D deficiency and normal urinary excretion of cyclic AMP might suggest another
      tubular defect in phosphate transport.

PMID- 11340358
TI  - Diagnosis of glomerular haematuria by imagecytometry of urinary red cells.

PMID- 11340357
TI  - Prognosis of patients with rounded atelectasis undergoing long-term hemodialysis.
AB  - We present 4 patients undergoing hemodialysis in whom thoracic computed
      tomography (CT) suggested a diagnosis of rounded atelectasis (RA) with pleural
      effusion. The clinical setting and follow-up CT of all 4 patients confirmed this
      diagnosis. The pleural fluid of each appeared serosanguineous or hemorrhagic and
      predominantly consisted of lymphocytes. Biochemical analysis of this fluid
      revealed high levels of total protein, lactate dehydrogenase and glucose.
      Bacterial culture and polymerase chain reaction for Mycobacterium tuberculosis
      DNA was negative. Pleural biopsy specimens from 2 of the 4 patients showed
      evidence of fibrinous change and mesothelial cell hyperplasia. Pleural effusion
      from all 4 patients did not respond to either fluid restriction or aggressive
      hemodialysis-induced dehydration. The subsequent clinical course and
      thoracentesis were repeated, and in 1 patient, this was followed by tetracycline
      pleurodesis. However, 2 patients died during pre-pleurodesis and 1 died during
      post-pleurodesis, all due to respiratory failure. We propose that the clinical
      setting and follow-up thoracic CT and thoracentesis of patients receiving long
      term hemodialysis confirmed a diagnosis of rounded atelectasis with uremic
      pleural effusion. We also propose that the prognosis of patients with refractory
      pleural effusion receiving long-term hemodialysis would be improved by early
      pleurodesis.

PMID- 11340359
TI  - Dehydroepiandrosterone sulfate and estradiol in men with diabetic nephropathy.

PMID- 11340360
TI  - Neurotransmitter and hormonal background of hostility in anorexia nervosa.
AB  - Marked hostility toward relatives, therapists and friends is very frequently
      observed in anorexia nervosa (AN) as expression of outward-directed
      aggressiveness which interferes with the therapeutic programs of the patients.
      With the purpose to investigate this aspect of the disorder and its biological
      background, we studied in anorexics some neurotransmitter-hormonal secretions
      which are known to modulate aggressivity-hostility by measuring plasma
      concentrations of total (TT) and free testosterone (FT), total estrogens (TE),
      the TT/E and FT/TE ratios, and the serotonergic function by measuring basal
      prolactin (PRL) levels and responses to stimulation with the specific serotonin
      (5-HT)-releasing agent D-fenfluramine (D-Fen). In 13 women with AN, 5 of the
      restricted (AN-R) and 8 of the bingeing/purging type (AN-BP) in an active phase
      of the disease, and in 13 healthy controls matched for sex and age, we measured
      hostility by the SCL-90 scale (subscale items 11, 24, 63, 67, 74, 81). Basal TT,
      FT, TE, TT/TE, FT/TE, PRL values and PRL responses to D-Fen and to saline
      administration were measured radioimmunologically in AN patients and controls.
      Hostility was significantly higher in AN patients than in controls, TT, FT and TE
      concentrations were significantly lower in AN patients than in controls, TT/TE
      ratio was significantly higher in AN patients than in controls, and FT/TE ratio
      was not different in the two groups. In AN patients and controls, hostility
      correlated positively with TT and FT values. Basal PRL values and responses to D
      Fen administration were significantly lower in anorexics than in controls, but
      they did not correlate with the degree of hostility in either patients or
      controls. In conclusion, hostility is higher than normal in anorexics, and its
      severity seems to be linked to the secretion of FT and not to the alterations in
      the 5-HT function.

PMID- 11340361
TI  - Excess tryptophan hydroxylase 17 779C allele in surviving cotwins of monozygotic
      twin suicide victims.
AB  - OBJECTIVE: To evaluate the relationship of the tryptophan hydroxylase (TPH)
      genotype to suicidality by the study of surviving monozygotic (MZ) cotwins of
      twins who committed suicide. METHOD: Twenty-four surviving Swedish MZ twins whose
      MZ cotwins had committed suicide were compared to 158 demographically sampled
      Swedish general population controls for TPH alleles. We also examined serotonin
      transporter alleles. RESULTS: The living MZ cotwins of suicide victims had a
      significantly higher TPH 17 779C allele frequency than controls. No significant
      difference was observed for serotonin transporter alleles. CONCLUSION: These
      results, in a small sample, suggest the possibility that the 17 779C allele of
      the TPH gene may be associated with an increased risk of suicide. Further studies
      in larger samples are needed.

PMID- 11340362
TI  - Polymorphisms in the promoter and coding regions of the synapsin III gene. A lack
      of association with schizophrenia.
AB  - The human synapsin III gene, located on chromosome 22q12-13, has previously been
      reported to indicate a susceptibility for schizophrenia. Noval rare variants
      (Thr136Thr in exon 3, Pro468Ser, Glu525Gln and Pro534Leu in exon 12, and 1769 G/C
      in the untranslated region of exon 13) were found in addition to the polymorphic
      variant (-196 G/A in the promoter region). No significant differences in
      genotypic or allelic frequencies of the -196 G/A polymorphism were found between
      87 unrelated schizophrenic patients and 100 healthy controls, even when the
      patients were diagnostically subdivided into subtypes and course specifiers.
      Furthermore, allelic frequencies of the GATG repeat in intron 1 were not
      significantly different between the patients and the controls. These results
      suggest that synapsin III gene polymorphisms are not associated with
      schizophrenia.

PMID- 11340363
TI  - Differential effects of age on brain gray matter in bipolar patients and healthy
      individuals.
AB  - This study examined possible differences in total gray and white matter brain
      content in bipolar patients and healthy individuals, and their relationship with
      age. 22 DSM-IV bipolar patients and 22 healthy controls underwent a 1.5-tesla
      Spoiled Gradient Recalled Acquisition (SPGR) MRI. Evaluators blind to patients'
      identities measured total brain, gray and white matter volumes using a semi
      automated software. No differences were found for total brain volume, gray matter
      or white matter volumes between bipolar patients and healthy controls (MANCOVA,
      age as covariate, p > 0.05). Age was inversely correlated with total gray matter
      volume in patients (r = -0.576, p = 0.005), but not in controls (r = -0.193, p =
      0.388). Our findings suggest that any existing gray matter deficits in bipolar
      disorder are likely to be localized to specific brain regions, rather than
      generalized. The inverse correlation between age and brain gray matter volumes in
      bipolar patients, not present in healthy controls, in this sample of mostly
      middle-aged adults, could possibly indicate more pronounced age-related gray
      matter decline in bipolar patients, and may be of potential relevance for the
      pathophysiology of the disorder.

PMID- 11340364
TI  - Polymorphisms in the dopamine, serotonin, and norepinephrine transporter genes
      and their relationship to temperamental dimensions measured by the Temperament
      and Character Inventory in healthy volunteers.
AB  - There is evidence for an association between polymorphisms of monoamine
      transporter genes and temperamental personality traits. Recent findings have
      shown that interaction of allelic variants of the different genes may contribute
      to the personality factors. We studied the association between temperamental
      personality dimensions measured with the Temperament and Character Inventory
      (TCI) and polymorphisms of the dopamine (DAT), norepinephrine (NET) and serotonin
      (5-HTT) transporter genes in 127 healthy Polish volunteers. There were no
      significant differences between means of TCI temperamental dimensions (novelty
      seeking, reward dependence, persistence and harm avoidance) and the transporter
      genes compared by ANOVA. There were some significant associations between
      genotypes and TCI subdimensions. Individuals carrying the A9/A9 DAT genotype have
      lower RD4 scores (dependence vs. independence) than A10/A10 individuals (3.0 +/-
      1.4 vs. 3.5 +/- 1.3); p = 0.01. Examining 5-HTT gene promoter polymorphism,
      heterozygous individuals (l/s) and individuals with 44-bp deletion (s/s) scored
      significantly lower in the HA1 subdimension (anticipatory worry and pessimism vs.
      uninhibited optimism; 4.3 +/- 2.3 vs. 5.5 +/- 2.6) in comparison with individuals
      without deletion (l/l); p = 0.021. The NET transporter gene polymorphism showed
      no significant association with any of the temperamental TCI subdimensions.

PMID- 11340365
TI  - Time course of intranasally administered cholecystokinin-8 on central nervous
      effects.
AB  - The gut and brain peptide cholecystokinin (CCK) exerts a number of central
      nervous effects. Among them are effects on attention and stimulus processing as
      revealed by modulations of event-related potentials (ERPs). In the present study
      the time course of central nervous effects after an intranasal administration of
      CCK-8 was investigated by means of ERPs. ERPs were recorded in an oddball
      paradigm 15, 30, 60, 90, 120, and 240 min after administration. Following the
      double-blind intranasal administration of CCK-8 and placebo, the late positive
      complex (LPC) of the ERP was significantly increased following CCK-8 compared to
      placebo. This effect was more pronounced in women than in men. The enhancement of
      the LPC by intranasal CCK-8 was not restricted to a specific recording time but
      reached its maximum 120 min after administration in men and women. Moreover,
      results tentatively indicate that 30 min after administration of CCK-8 the LPC
      increased only in women but not in men. The early effect of intranasal CCK-8 on
      LPC in women is unlikely to be caused by changes in plasma CCK-8 levels and
      suggests a direct nose-brain pathway.

PMID- 11340366
TI  - Regional cerebral blood flow in patients suffering from post-traumatic stress
      disorder.
AB  - OBJECTIVE: The aim of the study was to determine whether regional cerebral blood
      flow in survivors of torture suffering from post-traumatic stress disorder (PTSD)
      differed significantly from that in healthy controls. METHOD: We examined the
      cerebral regional distribution of 99m-technetium-hexamethylpropyleneamineoxime
      (HMPAO) using single photon emission computed tomography (SPECT) in 8 patients
      and in 8 healthy controls. A semi-quantitative analysis was performed in which
      symmetrical regions of interest (ROI) were drawn in all subjects. RESULTS:
      Regional blood flow was markedly more heterogeneous in patients suffering from
      PTSD than in healthy controls. The differences are significant. CONCLUSION:
      Severe psychological trauma induced by torture can cause neurobiologic
      alterations that may contribute, even years after the original trauma, to a
      number of complaints commonly expressed by patients suffering from PTSD.

PMID- 11340367
TI  - Eeg alpha rhythm and glucose metabolic rate in the thalamus in schizophrenia.
AB  - Positron emission tomography with uptake of [(18)F]fluorodeoxyglucose (FDG) and
      quantitative EEG were simultaneously performed in 18 medication-free patients
      with schizophrenia and in 13 normal volunteers. Subjects performed the Continuous
      Performance Task (CPT) during FDG uptake. Correlations were calculated between
      alpha power during the CPT and glucose metabolic rate (GMR) in thalamic regions
      and between alpha power during the CPT and GMR in occipital cortices. Regression
      analyses were used to describe the prediction of GMR in the occipital cortices
      and in the thalamic regions of occipital alpha power. In normal controls, we
      found (1) significant negative correlations between absolute alpha power and GMR
      in the left occipital cortex, (2) significant positive correlations between
      normalized alpha power and GMR in the right and left lateral thalamus and (3)
      combined effects of GMR in the thalamic regions and the occipital cortices on
      alpha power, which accounted for 98% of the variance of alpha power. In patients
      with schizophrenia, we found no significant correlations between alpha power and
      GMR in the occipital cortices or between alpha power and GMR in the thalamic
      regions. Correlation coefficients between absolute alpha power and GMR in the
      left occipital cortex and between normalized alpha power and GMR in the left
      lateral thalamus were significantly different in normal subjects compared to
      schizophrenic patients. The present findings provide evidence for involvement of
      the thalamus in the generation of alpha rhythm in humans. Furthermore, the
      present results suggest differences in thalamocortical circuits between normal
      controls and schizophrenic subjects.

PMID- 11340368
TI  - Short-term rivastigmine treatment reduces EEG slow-wave power in Alzheimer
      patients.
AB  - The effects of a 5-day treatment with rivastigmine on the resting EEG power
      spectrum were studied in 15 mildly to moderately ill Alzheimer patients. In these
      patients, beta power was positively correlated with cognitive performance and
      negatively correlated with functional impairment. Rivastigmine produced a
      decrease in delta and theta power with no effect of hemisphere and electrode
      position. Delta power decrease reflects the cerebral cholinergic action of
      rivastigmine and may thus allow a quantitative assessment of its CNS effects.

PMID- 11340369
TI  - The evolving role of gemcitabine in the management of breast cancer.
AB  - Despite the common clinical use of numerous active cytotoxic agents for breast
      cancer therapy, and the combinations that are derived from them, the median
      survival for patients with metastatic breast cancer has not been dramatically
      improved over the past two decades. Furthermore, when the expected outcome of
      treatment is not cure, optimizing the dynamic equilibrium between chemotherapy
      induced side effects and the benefits attributable to chemotherapy-mediated
      relief of cancer-related symptomatology becomes paramount. The search for active
      agents to this end has recently included the clinical evaluation of the novel
      nucleoside analogue gemcitabine (2',2'-difluorodeoxycytidine). This review
      summarizes the recent and current development of this agent.

PMID- 11340370
TI  - Hormone replacement therapy after treatment of breast cancer: effects on
      postmenopausal symptoms, bone mineral density and recurrence rates.
AB  - PURPOSE: Breast cancer (BC) is the most frequent female carcinoma and the major
      cause of death in women aged 35--50 years. The total number of patients surviving
      BC and especially the morbidity rate of patients below the age of 55 years has
      increased significantly in the last several years. As a consequence, the number
      of BC patients suffering from the long-term effects of estrogen deficiency due to
      adjuvant treatment is increasing. At present, hormone replacement therapy (HRT)
      following BC treatment is applied individually and mainly depends on the severity
      of postmenopausal symptoms (PMS) experienced by these patients. PATIENTS AND
      METHODS: In a retrospective study (total n = 185 BC patients, 64 with and 121
      without HRT), the effect of HRT during or after adjuvant therapy [chemotherapy
      and/ or (anti-) hormonotherapy] has been investigated. The surveillance period
      was up to 60 months. Evaluated were HRT effects on (1) PMS measured by a
      comprehensive life quality questionnaire, (2) bone mineral density (BMD) measured
      by osteodensitometry and (3) morbidity as well as mortality rates. RESULTS: Both
      groups did not differ with regard to tumor stage, lymph node involvement,
      metastasis, grading, and steroid hormone receptor status. A reduction in PMS was
      significant in women taking HRT (p < 0.001), especially in the subgroup of women
      < or =50 years (p < 0.0001). For both age groups, the median reduction in BMD (z
      score) was less in women receiving HRT (< or =50 years: without HRT -1.99 vs.
      with HRT -0.95, p < 0.05; >50 years: without HRT -2.29 vs. with HRT -1.19, p <
      0.01). There were no statistically significant differences regarding morbidity
      and mortality (p = 0.29). CONCLUSION: In this study of BC patients, the use of
      HRT shows positive effects on PMS and BMD. There was no significant influence on
      morbidity or mortality. However, a reevaluation of HRT in the routine management
      of BC patients should await the results of prospective randomized trials.

PMID- 11340371
TI  - A dose-finding study of irinotecan (CPT-11) plus a four-day continuous 5
      fluorouracil infusion in advanced colorectal cancer.
AB  - OBJECTIVE: Irinotecan (CPT-11) has shown considerable activity in colorectal
      cancer, and its combination with 5-fluorouracil (5-FU) represents an attractive
      approach. A phase I study was conducted to determine the maximum tolerated dose
      (MTD) and the dose-limiting toxicities (DLTs) of CPT-11 in combination with a
      continuous infusion of 5-FU for 4 days. METHODS: Forty-two patients with
      histologically confirmed metastatic colorectal cancer who had not received prior
      treatment for advanced disease were enrolled. The patients' median age was 64
      years; 26 (62%) patients were men, and the performance status (WHO) was 0 in 26
      (62%) patients, 1 in 15 (36%) and 2 in 1 (2%). Twenty-two (52%) patients had 2 or
      more metastatic sites. CPT-11 (starting dose 200 mg/m(2)) was administered as a
      30-min intravenous infusion with increments of 50 mg/m(2) on day 4. 5-FU
      (starting dose 400 mg/m(2)) was administered as a 4-day continuous intravenous
      infusion with increments of 50 mg/m(2) on days 1-4. Treatment was repeated every
      4 weeks. RESULTS: The MTD of the combination was found to be 600 mg/m(2) for 5-FU
      and 350 mg/m(2) for CPT-11. Neutropenia, febrile neutropenia and delayed diarrhea
      were the DLTs. Grade 3/4 neutropenia was observed in 22 (13%) out of 169
      administered treatment cycles, febrile neutropenia in 7 (4%) and grade 3/4
      diarrhea in 20 (12%). Other toxicities were mild. Among 36 patients evaluable for
      response, partial response was achieved in 8 (22%), stable disease in 12 (33%)
      and progressive disease in 16 (44%) patients. Responses were mostly seen at the
      higher dose levels. CONCLUSIONS: The combination of a 4-day continuous infusion
      of 5-FU followed by CPT-11 represents an active and well-tolerated regimen for
      patients with colorectal cancer. This regimen merits further evaluation in phase
      II studies.

PMID- 11340372
TI  - Dose-dense sequential adjuvant chemotherapy with epirubicin, paclitaxel and CMF
      in high-risk breast cancer.
AB  - Dose-dense sequential chemotherapy appears to be a promising approach in the
      management of patients with operable breast cancer. We evaluated the tolerability
      of such a novel chemotherapeutic regimen in high-risk patients. From February
      1995 until September 1997, 49 women with histologically confirmed breast cancer
      and > or =10 involved axillary nodes were treated postoperatively with three
      cycles of epirubicin (110 mg/m(2)) followed by three cycles of paclitaxel (250
      mg/m(2) in a 3-hour infusion) followed by three cycles of 'intensified' CMF
      (cyclophosphamide 840 mg/m(2), methotrexate 57 mg/m(2), fluorouracil 840 mg/m(2);
      E-T-CMF). All cycles were repeated every 2 weeks with G-CSF support. Ovarian
      ablation with monthly injections of triptorelin for 1 year was performed in
      premenopausal patients and tamoxifen was prescribed for 5 years to all women with
      positive receptor status after the completion of chemotherapy. A total of 456
      cycles of chemotherapy were administered, 363 (80%) of them at full dose. Forty
      seven (96%) patients received all 9 cycles of chemotherapy. Relative dose
      intensity of epirubicin was 0.98, of paclitaxel 0.97, of cyclophosphamide 0.99,
      of methotrexate 0.98 and of fluorouracil 0.99. Grade 3--4 toxicities included
      anemia (8%), leukopenia (8%), peripheral neuropathy (6%), neutropenia (4%),
      thrombocytopenia (4%), stomatitis (2%), diarrhea (2%), fatigue (2%) and
      hypersensitivity reaction (2%). Febrile neutropenia occurred in 2 patients.
      Alopecia was universal. After a median follow-up of 3 years, 11 women (22%)
      relapsed and 4 (8%) died. The 3-year actuarial disease-free survival rate was 72%
      and the 3-year overall survival rate 90%. The E-T-CMF regimen is well tolerated,
      as adjuvant treatment, in patients with operable breast cancer with promising
      activity and deserves further evaluation in phase III studies.

PMID- 11340373
TI  - Adjuvant chemotherapy with high-dose cyclophosphamide, etoposide and cisplatin
      intensification without progenitor cell support in breast cancer patients with
      ten or more involved nodes: 5-year results of a pilot trial.
AB  - OBJECTIVES: The purpose of this study was to evaluate the clinical efficacy and
      tolerability of high-dose (HD) chemotherapy with growth factor support in primary
      breast cancer with extensive nodal involvement. PATIENTS AND METHODS: Fifty-three
      patients with ten or more involved nodes were recruited and were given three
      cycles of standard-dose fluorouracil, epidoxorubicin and cyclophosphamide
      followed by one single course of high-dose CEP (cyclophosphamide, etoposide and
      cisplatin). No autologous progenitor support was used. RESULTS: Five-year
      actuarial disease-free and overall survival were 40 and 60%, respectively. High
      dose CEP required a median of 22 days of hospitalization and was associated with
      grade G3--4 nausea and vomiting in two thirds of the cases. Hematological
      toxicity was comparable to that of high-dose therapies delivered with autologous
      progenitor support. No therapy-related mortality was observed. CONCLUSIONS The
      efficacy of treatment was comparable to the best results of conventional therapy,
      with only a trend for improved survival. High-dose CEP was feasible with
      acceptable toxicity. Although this regimen does not require stem cell harvesting
      and storage, it requires clinical support comparable to autotransplantation
      procedures and side effects are not so manageable to recommend its use outside
      specialized units.

PMID- 11340374
TI  - Three-year results of the first educational and early detection program for
      testicular cancer in Hungary.
AB  - OBJECTIVE: To determine whether a testicular self-examination-based early
      detection program may help in the early diagnosis of testicular cancer. METHODS:
      Advertisements were placed in the media describing the early signs of testicular
      cancer, the risk factors, the correct method of self-examination and the
      importance of early detection. Between April 1995 and April 1998, 5,056 men
      underwent physical and ultrasound examination of the testicles, and in case of
      suspicious findings tumor markers were checked. RESULTS: Testicular tumors were
      found in 1.28% of the men with symptoms. No tumors were found in men without
      symptoms or in men with pain, sensitivity to palpation, or complaints unrelated
      to the testicle. Of those with a palpable lump or swollen testicle, 4.5 and 3.9%
      were found to have a tumor. In total, 28 testicular cancers (15 seminomas and 13
      nonseminomas) in 26 volunteers and 4 benign tumors were detected. The occurrence
      of cancer was most frequent in the age group of 15--40 years (1.6%). CONCLUSION:
      The rate of cancer detection and the detected seminoma rate in the program are
      not sufficient to justify a widespread early detection program for testicular
      cancer (examination of men who reveal testicular abnormalities by self
      examination) despite the increased tumor incidence. Early diagnosis should be
      based on an educational program for the population at risk, the training of staff
      engaged in the health care of the young, and the use of early ultrasound
      examination in men with palpable lumps and swollen testicles, especially in young
      men.

PMID- 11340375
TI  - Vinorelbine-based regimens as salvage treatment in patients with advanced non
      small cell lung cancer: two parallel multicenter phase II trials.
AB  - Two parallel phase II trials were conducted in order to evaluate the efficacy and
      toxicity of vinorelbine-ifosfamide (VNB-IFX) and vinorelbine-carboplatin (VNB-C)
      combinations as salvage treatment in patients with advanced non-small cell lung
      cancer (NSCLC). PATIENTS AND METHODS: Patients failing platinum-based front-line
      chemotherapy were enrolled in the VNB-IFX trial while patients failing non
      platinum-containing chemotherapy were treated with VNB-C. Twenty-nine patients
      were treated with VNB-IFX [median age: 59 years; performance status, PS (WHO) 0-
      1: 72% and disease stage IV: 79%] and 37 with VNB-C [median age: 61 years; PS
      (WHO) 0--1: 51% and stage IV: 84%]. Patients received vinorelbine 25 mg/m(2) i.v.
      on days 1 and 8 and ifosfamide 1.6 g/m(2) i.v. on days 8--10 with uroprotective
      mesna, in cycles of 28 days. G-CSF (5 microg/kg/day s.c.) was administered
      prophylactically on days 11--16 or until hematological recovery. The VNB-C
      regimen consisted of carboplatin 300 mg/m(2) on day 1 and vinorelbine 30 mg/m(2)
      on days 1 and 8 every 28 days. RESULTS: Twenty-six patients were evaluable for
      response in the VNB-IFX trial and 29 in the VNB-C. Overall response rates (intent
      to-treat analysis) were 3% (1 patient; duration of response: 3 months) for the
      VNB-IFX and 16% (median duration of response: 7.5 months) for the VNB-C
      combination. The median time to progression and survival for patients receiving
      VNB-IFX were 4.5 and 6 months (1-year survival: 19%), respectively; the
      corresponding values for VNB-C were 9.0 and 8.5 months (1-year survival: 38%).
      The median survival of patients achieving stable disease was 10 (VNB-IFX) and
      14.5 (VNB-C) months. Grade 3--4 neutropenia occurred in 4 (13%) of the patients
      treated with VNB-IFX; all cases were complicated with fever. Grade 3--4
      neutropenia was documented in 13 (35%) patients in the VNB-C trial; 6 (16%)
      developed neutropenic fever. There were no treatment-related deaths. Non
      hematologic toxicity for the VNB-IFX and VNB-C regimens was mild with grade 2--3
      peripheral neurotoxicity occurring in 3 (10%) and 7 (19%) patients, and grade 2-
      3 asthenia in 11 (38%) and 18 (48%) patients, respectively. CONCLUSION: Both
      combinations were associated with a tolerable toxicity profile. VNB-C
      demonstrated notable activity in patients previously treated with a taxane-based
      regimen, whilst VNB-IFX failed to produce a significant response rate in patients
      treated with platinum-containing chemotherapy. Stabilization of disease was
      associated with a favorable survival in both studies.

PMID- 11340376
TI  - Expression and clinical significance of the G1-S modulators in intrahepatic
      cholangiocellular carcinoma.
AB  - OBJECTIVE: To elucidate the clinical roles of G1-S modulators in
      cholangiocellular carcinoma (CCC). METHODS: We performed immunohistochemistry
      using antibodies against the retinoblastoma gene product (pRb), p16, p21, p27,
      p53 and cyclin D1 for 41 cases of CCC as well as normal bile ducts. RESULTS: The
      p27 labeling index (LI) was significantly higher in cases without lymph node
      metastasis than in normal bile ducts, but it decreased greatly in cases with
      lymph node metastasis. It was inversely related to the Ki-67 LI. The p16 LI also
      showed a relationship with lymph node metastasis, but not with the Ki-67 LI. The
      p21 LI was even higher in poorly differentiated cases and showed a direct
      relationship with the Ki-67 LI, although it is a negative regulator of the cell
      cycle. pRb expression did not correlate with any clinicopathological features.
      Cyclin D1 overexpression was more frequently observed in cases with poor or
      moderate differentiation and with lymph node metastasis. Cyclin D1 overexpression
      and aberrant p53 expression showed direct relationships with the Ki-67 LI.
      CONCLUSIONS: These results suggest that in CCC: (1) p27 expression reflects the
      biological character of the carcinoma and may regulate its progression; (2)
      cyclin D1 plays a crucial role in cell cycle progression, and (3) aberrant p53
      expression has some effect on CCC cell proliferating activity.

PMID- 11340377
TI  - Insulin-like growth factor binding protein-3 predicts survival from acute
      childhood leukemia.
AB  - OBJECTIVE: To investigate whether the three principal components of the insulin
      like growth factor (IGF) system, IGF-1, IGF-2 and IGF binding protein-3 (IGFBP
      3), are associated with survival from childhood leukemia. PATIENTS AND METHODS:
      116 children, 0--14 years old, with newly diagnosed and bone-marrow-biopsy
      confirmed acute childhood leukemia between 1993 and 1996 were followed up until
      death or March 31, 1998. IGF-1, IGF-2 and IGFBP-3 were measured at diagnosis and
      clinical data, including presence of hepatosplenomegaly and number of white blood
      cells, were available. RESULTS: After controlling for gender, age, indicators of
      clinical severity and the other measured components of the IGF system there was a
      statistically significant (p < 0.05) inverse association of IGFBP-3 with
      survival. An increment of one standard deviation in IGFBP-3 was associated with a
      65% reduction of the death hazard among the children with leukemia. Neither IGF-1
      nor IGF-2 was associated with survival in this data set. CONCLUSION: The
      presented empirical evidence in conjunction with the fact that IGFBP-3 modulates
      IGF-1 and IGF-2 bioavailability and is likely to have proapoptotic effects makes
      this compound a plausible independent predictor of survival from childhood
      leukemia.

PMID- 11340378
TI  - Imbalance between neutral endopeptidase 24.11 and endothelin-1 expression in
      human endometrial carcinoma.
AB  - OBJECTIVES: Neutral endopeptidase 24.11 (NEP)/CD10 is a cell-surface peptidase
      that degrades various bioactive peptides including endothelin-1 (ET-1). This
      enzyme is known to play a role in maintaining ET-1-regulated vascular homeostasis
      in the normal human endometrium. The purpose of the present study was to
      investigate the expression and localization of NEP and ET-1 in neoplastic
      endometria, and also to clarify the correlation of their expression with the
      tumor grade of endometrial carcinoma. METHODS: Immunohistochemical analysis for
      NEP and ET-1 expression was performed on paraffin-embedded tissue sections of 7
      normal endometria (after menopause), 5 atypical endometrial hyperplasias (AEH),
      and 32 endometrial endometrioid adenocarcinomas. RESULTS: In normal endometrium
      and AEH, NEP immunoreactivity was detected in stromal cells, but not in glandular
      cells. In contrast, ET-1 immunoreactivity was detected in both glandular and
      stromal cells. In the stromal cells of grade 1 endometrial adenocarcinoma, NEP
      was detected at high or moderate quantities. However, significantly decreased NEP
      immunoreactivity was observed in the stromal cells of grade 2 and 3
      adenocarcinomas. However, NEP was not immunostained in adenocarcinoma cells
      except for the lesions of squamous differentiation. ET-1 immunoreactivity was
      weakly detected in the stromal cells of grade 1 adenocarcinoma, but the intensity
      of ET-1 staining increased with advancing tumor grade. The ratio of the staining
      scores of stromal ET-1 to stromal NEP was positively correlated with the tumor
      grade. CONCLUSIONS: These findings demonstrate that NEP expression in the stromal
      cells of endometrial adenocarcinoma is downregulated, while stromal ET-1 is
      upregulated, with increasing tumor grade. The present findings also suggest that
      NEP may play a role in the regulation of neoplastic transformation, tumor
      progression, and differentiation in endometrial neoplasms, possibly by degrading
      certain peptide growth factors such as ET-1.

PMID- 11340379
TI  - Loss of imprinting of long QT intronic transcript 1 in colorectal cancer.
AB  - Loss of imprinting (LOI) of the insulin-like growth factor 2 (IGF2) and H19 genes
      on human chromosome 11 has been found not only in childhood tumors but also in
      common adult cancers including colorectal cancer. Recently, a transcript called
      LIT1 (long QT intronic transcript 1) has been identified within the KvLQT1 locus
      on chromosome 11. LIT1 is expressed preferentially from the paternal allele and
      is transcribed in most human tissues. LOI of LIT1 was found in a considerable
      number of Beckwith-Wiedemann syndrome (BWS) patients, suggesting that it is
      associated with the etiology of BWS. Since LOI of IGF2 was observed in
      association with overexpression of IGF2 in colorectal cancer in our previous
      study, we examined the status of genomic imprinting of LIT1 and H19 in comparison
      with IGF2 in colorectal cancer. We examined 44 surgically dissected colorectal
      cancer tissues. Ten of them represented informative cases for LIT1. None of these
      patients exhibited loss of heterozygosity (LOH) of LIT1, and LOI of LIT1 was
      observed in 4 of the 10 (40%) informative patients, but not in non-cancerous
      tissues. Neither LOH nor LOI of H19 was observed. LOI of IGF2 was observed in 4
      of 18 (22%) informative patients. These results suggest that LOI of LIT1 is
      frequently observed in colorectal cancer and may be a useful marker for diagnosis
      of colorectal cancer.

PMID- 11340380
TI  - Role of the basement membrane in tumor cell dormancy and cytotoxic resistance.
AB  - OBJECTIVES AND METHODS: Tumor dormancy and resistance to cytotoxic agents are key
      limiting events in the treatment of malignant diseases. To determine whether both
      are influenced by the extracellular milieu in which tumors reside, HT1080 human
      fibrosarcoma, MCF-7 breast carcinoma and OSCORT osteosarcoma cell proliferation,
      viability, apoptosis and cytoreductive-treatment-induced death were investigated
      in the presence or absence of extracellular matrix (ECM). RESULTS: ECM-adherent,
      but not plastic-adherent HT1080 cells formed a multicellular network accompanied
      by reduced proliferation and lowered DNA synthetic capacity. The number of cells
      in S-phase was dramatically reduced. Viable cells entered a state of dormancy
      reminiscent of that observed in the step of metastasis after extravasation, i.e.
      prior to the initiation of progressive growth. Such ECM-induced dormancy could be
      reversed by plating cells on plastic, but only after a 48-hour lag period. No
      difference was indicated in clonogenicity of HT1080 cells originated from plastic
      or ECM gel. However, the cells released from ECM gel showed significantly reduced
      migration ability. The resistance of anchored cells against cytotoxic damage was
      increased by ECM gel. Examination of cytoreductive treatment revealed that ECM
      adherence at the time of injury is partially protective, a property which was
      also moderately apparent when injured cells were transferred to the basement
      membrane. CONCLUSIONS: Taken together, these results suggest that the ECM plays a
      key role in tumor dormancy and cytotoxic resistance, both explorable at the
      molecular level using our in vitro model system.

PMID- 11340381
TI  - Effects of octreotide on liver metastasis and intrametastatic lipid peroxidation
      in experimental pancreatic cancer.
AB  - OBJECTIVES: In prospective clinical trials, octreotide improved the quality of
      life and survival time in patients with pancreatic cancer. In this study, we
      analyzed whether octreotide modulates the intrametastatic oxygen radical
      metabolism and might decrease liver metastasis in a model of pancreatic cancer.
      METHODS: Syrian hamsters received 0.9% NaCl or N-nitrosobis(2-oxopropyl)amine for
      3 months. Therapy was performed for 12 weeks by 0.9% NaCl or octreotide. Hamsters
      received a standard diet or were fed a high-fat diet. In the 25th week, pancreas
      and liver were examined macroscopically and histologically. The level of lipid
      peroxidation and the activity of glutathione peroxidase and superoxide dismutase
      were determined intrahepatically and intrametastatically. RESULTS: The number and
      size of liver metastases per animal were increased by high-fat diet and decreased
      by octreotide. While high-fat diet increased intrahepatic extrametastatic lipid
      peroxidation, octreotide decreased intrahepatic extrametastatic lipid
      peroxidation and increased intrametastatic lipid peroxidation. CONCLUSIONS:
      Octreotide decreases the number and size of liver metastases in chemically
      induced pancreatic cancer in Syrian hamsters. Possible mechanisms are the
      prevention of high lipid peroxidation in non-metastatic liver as well as the
      increase in intrametastatic lipid peroxidation, leading to loss of integrity of
      spread tumor cells.

PMID- 11340383
TI  - Normal range of exophthalmos values on orbit computerized tomography in Koreans.
AB  - The value of parameters in Hertel's exophthalmometry was measured by using orbit
      computerized tomography (CT) in this study. We selected images that revealed the
      center of the lens, the largest eyeball contour and the optic canal on the axial
      view of orbit CT. Parameters of exophthalmometry on orbit CT were the distance
      between the lateral orbital rims of both eyes (A), the shortest distance from the
      corneal center to line A (B), the B/A ratio, the distance between the lateral
      orbital rim and the medial orbital rim (C), the length of the line passing
      through the lens center from the apex to line C (D) and the D/C ratio. To compare
      the center position of the eye, we measure the axial length (E) and the longest
      distance between the corneal apex and the posterior pole (F) which is parallel to
      line B. We also calculated B-F/2 and Hertel-F/2 in order to know if there is a
      difference between measurements of orbit CT and of Hertel's exophthalmometer.
      Subjects were classified into group 1 (aged 8-13 years old) and group 2 (aged 20
      years old more). Sixteen subjects were enrolled in group 1 (32 eyes). In group 2,
      100 subjects were male (200 eyes) and 35 were female (70 eyes). In group 1, the
      mean value was 89.94 mm for A, 13.49 mm for B, 35.13 mm for C, 10.64 mm for D,
      24.40 mm for E, 24.20 mm for F, 0.15 for the B/A ratio and 0.30 for the D/C
      ratio. In group 2, the mean value was 100.93 mm for A, 15.03 mm for B, 38.78 mm
      for C, 12.03 mm for D, 24.62 mm for E, 24.33 mm for F, 0.15 for the B/A ratio and
      0.31 for the D/C ratio. There was a statistically significant difference between
      the two groups for parameters A, B, C and D (p = 0.001), but no significant
      difference for the B/A (p = 0.239) and D/C ratios (p = 0.803). In the males and
      females of group 2, there was a statistically significant difference for the B/A
      ratio (p = 0.028). We suggest that the value of the D/C ratio (0.30-0.31) could
      be used as the index of protrusion. The normal values of exophthalmometry
      parameters measured by orbit CT could also be helpful to evaluate the exact
      protrusion in orbital diseases.

PMID- 11340382
TI  - Biodegradable polymers for ocular drug delivery.
AB  - A variety of ocular drug delivery systems, including a controlled release of the
      drug, drug targeting, and penetration enhancement of the drug, have been
      investigated. Biodegradable polymers have been widely used as the drug carrier
      for controlled-release systems. Biodegradable polymers release the drug as they
      themselves degrade and are finally absorbed within the body. Several ocular drug
      delivery systems using different kinds of biodegradable polymers have been
      studied. In this article, we describe the fundamental mechanisms of drug delivery
      systems, polymer erosion and drug release, and then review those systems using
      the most popular biodegradable polymers, poly(lactic acid) and poly(lactic
      glycolic acid).

PMID- 11340384
TI  - Value of positron emission tomography in the diagnosis of malignant ocular
      tumors.
AB  - PURPOSE: To address the question whether positron emission tomography (PET) can
      identify malignant ocular tumors. METHODS: In patients with ocular tumors, PET
      was performed using the incorporation of the glucose analogue (18)F-2-fluoro-2
      deoxy-D-glucose. The diagnosis of the ocular lesions was based on conventional
      diagnostic procedures including histologic examination. RESULTS: Nineteen
      patients with a mean age of 62.8 +/- 14.2 years were included in this study. Nine
      patients with a mean age of 62.9 +/- 13.1 years displayed the presence of a
      malignant tumor including metastatic lesions (4), malignant melanomas (4) and
      squamous cell carcinoma (1). Additionally, 10 patients with a mean age of 62.8 +/
      15.9 years with benign lesions were studied. There was a statistically
      significant difference (p = 0.012) in tumor height and tumor volume, but not in
      tumor diameter between benign and malignant lesions. The smallest PET positive
      lesion measured 7 x 3 mm. PET was positive in 7 out of 9 malignant lesions and
      negative in all 10 benign lesions, i.e. there was no false-positive and two false
      negative results. The two false-negative tumors represented malignant melanomas
      of the choroid. Additionally, results of the PET examination were independent of
      tumor size. CONCLUSION: PET seems to be of limited value for the diagnosis of
      malignant melanoma of the choroid, i.e. a negative result does not exclude a
      malignant process.

PMID- 11340385
TI  - Involutional entropion surgery: a modified technique.
AB  - PURPOSE: A study to evaluate the effectiveness of a modified procedure to correct
      involutional entropion. METHODS: Seventeen cases of involutional entropion
      underwent surgery and had a postoperative follow-up of 18 months. The authors
      describe a technique of vertically shortening the anterior lamella (skin and
      orbicularis muscle), using a blepharoplasty incision and reflection of a skin
      muscle flap. RESULTS: In 16 of 17 eyelids affected by involutional entropion,
      this operative procedure showed good functional outcome (good correction of the
      relation between lower eyelid edge and eyeball) and aesthetic outcome (no
      hypertrophic scar, dyschromia or unnatural folding of the skin). CONCLUSIONS: A
      correct approach to entropion surgery needs an accurate preoperative evaluation
      of the individual physiopathogenic factors. This procedure gives lasting
      functional and pleasing cosmetic results when preseptal orbicularis muscle
      override has been identified as the cause of senile entropion.

PMID- 11340386
TI  - Postoperative inflammation after cataract surgery in patients with rheumatoid
      arthritis.
AB  - The purpose of the present study was to assess the influence of preoperative
      activity of rheumatoid arthritis (RA) on early postoperative anterior chamber
      inflammation after phacoemulsification and intraocular lens implantation. Twenty
      three eyes in 18 patients were included in our study. On the first postoperative
      day, anterior chamber inflammation was observed in 11 eyes (47.8%). Five days
      after surgery, we found postoperative inflammation only in 1 eye (4.3%). Keratic
      precipitates were observed in 1 eye (4.3%) on the second postoperative day. We
      found no correlation between the extent of anterior chamber inflammation and the
      preoperative activity of RA. Postoperative anterior chamber inflammation was also
      not associated with the medical management of RA.

PMID- 11340387
TI  - Ocular attacks after phacoemulsification and intraocular lens implantation in
      patients with Behcet disease.
AB  - PURPOSE: To elucidate factors related to ocular inflammatory attacks after
      cataract surgery, limited to a single procedure of phacoemulsification and
      intraocular lens implantation, in patients with Behcet disease. METHODS: This
      retrospective study included 12 consecutive patients (16 eyes) with Behcet
      disease, who underwent phacoemulsification and intraocular lens implantation
      during 4 years from January 1995 to December 1998 at three institutions. Their
      medical records were reviewed, and factors related to the ocular attacks were
      analyzed. RESULTS: Four eyes of 3 patients experienced ocular attacks during 1
      year before cataract surgery, while 4 eyes of 4 patients developed ocular attacks
      during 1 year after the surgery. The development of ocular attacks after cataract
      surgery was significantly related with the presence of ocular attacks during 1
      year before the surgery (p = 0.0286, chi(2) test). The patients' age or gender,
      the duration of Behcet disease or oral medications for Behcet disease did not
      show any relationship with the presence or absence of ocular attacks after
      cataract surgery. The visual acuity improved in all patients after the surgery,
      including those who developed ocular attacks. CONCLUSIONS: The experience of
      ocular attacks during 1 year before cataract surgery is related to postoperative
      ocular attacks. Despite postoperative ocular attacks, phacoemulsification with
      intraocular lens implantation is a safe procedure to expect a good visual outcome
      in patients with Behcet disease.

PMID- 11340388
TI  - Familial chronic central serous chorioretinopathy.
AB  - Twenty-seven patients with characteristic, mostly bilateral, fundus lesions of
      chronic central serous chorioretinopathy (CSC) and a progressive course, and 80
      of their relatives, mainly siblings, were examined. Ophthalmologic examination
      included assessment of visual acuity, Amsler grid testing, ophthalmoscopy and
      fluorescein angiography. The fundus findings were classified as normal fundus,
      multiple areas of retinal pigment epithelium (RPE) atrophy or chronic CSC: RPE
      atrophy with leakage of fluorescein. In 14 (52%) of the 27 families, 1 or more
      relatives were affected. Thirty-five (44%) of the 80 investigated relatives had
      fundus lesions: 22 had chronic CSC in one eye, 20 of these had chronic CSC or RPE
      atrophy in the fellow eye. Thirteen relatives had RPE atrophy in one or both
      eyes. The mode of inheritance could not be established.

PMID- 11340389
TI  - Comparisons of intraocular-pressure- lowering efficacy and side effects of 2%
      dorzolamide and 1% brinzolamide.
AB  - Forty-one healthy volunteers were recruited for a study to compare the
      intraocular pressure (IOP)-lowering efficacy and side effects of 2% dorzolamide
      and 1% brinzolamide. In a randomized double-blind design, one eye received one
      drop of 2% dorzolamide and the other eye received one drop of 1% brinzolamide.
      The IOP and side effects were evaluated by Goldmann applanation tonometry and
      slit lamp biomicroscopy before administration, and 3, 7 and 14 days after the
      initial administration of eyedrops. The IOP decreased significantly from baseline
      for both drugs (p < 0.05). However, there were no statistically significant
      differences between 2% dorzolamide and 1% brinzolamide either before or after
      eyedrop administration (p > 0.05). The most frequent side effect was ocular pain
      in the case of 2% dorzolamide and blurred vision in 1% brinzolamide. The results
      suggested that 2% dorzolamide and 1% brinzolamide have similar IOP-lowering
      efficacies with different side effects

PMID- 11340390
TI  - Effects of topical vitamin E on keratocyte apoptosis after traditional
      photorefractive keratectomy.
AB  - PURPOSE: To evaluate the keratocyte apoptosis and effects of topical vitamin E on
      keratocyte apoptosis after photorefractive surgery. METHODS: Rabbits were divided
      into 7 groups, and all groups were compared with controls after epithelial
      scraping, epithelial scrape and photorefractive keratectomy (PRK) (traditional
      PRK), transepithelial PRK, production of a corneal flap with microkeratome and
      laser-assisted in situ keratomileusis (LASIK). The effects of topical Vitamin E
      treatment were investigated in the traditional PRK group. The terminal
      deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick-end labelling
      assay (to detect DNA fragmentation in situ) and light microscopy have been used
      to detect apoptosis in rabbit cornea. RESULTS: Transepithelial PRK induced
      minimal keratocyte apoptosis, less than in all other refractive surgical
      procedures. The greatest amount of keratocyte apoptosis was observed after
      traditional PRK (p = 0.001), therefore we tested the effects of topical vitamin E
      in this group. The number of apoptotic keratocytes significantly reduced after
      vitamin E therapy (p < 0.005). CONCLUSION: Keratocytes undergo apoptosis after
      refractive surgery in response to mechanical epithelial removal, preparing of
      corneal flap and excimer laser stromal photoablation. The topical application of
      vitamin E immediately after surgery can prevent keratocyte apoptosis, and this
      result suggests that free radicals may be partly responsible for keratocyte
      apoptosis after excimer laser keratectomy.

PMID- 11340391
TI  - Effects of contact lenses on corneal endothelium - a morphological and functional
      study.
AB  - PURPOSE: To study the corneal endothelial morphological changes and endothelial
      barrier function in contact lens wearers. METHODS: Specular microscopy and
      anterior segment fluorophotometry were performed on 116 controls (group 1) and 76
      daily wear soft contact lens wearers. Group 2 patients (n = 34) had been wearing
      contact lenses for less than 5 years and group 3 (n = 42) for more than 5 years.
      The relationship of corneal thickness, endothelial cell density, hexagonal cell
      percentage, coefficient of variation in cell area, corneal autofluorescence and
      corneal endothelial permeability to the contact lens wear duration was studied.
      RESULTS: The average corneal thickness of contact lens wearers did not differ
      significantly from controls (0.533 +/- 0.031, 0.538 +/- 0.044, 0.532 +/- 0.031 mm
      for groups 1, 2 and 3, respectively; p = 0.89). However, there was a significant
      tendency toward corneal thinning with a longer history of contact lens wear (r = 
      0.31, p = 0.002 in groups 2 and 3). The percentage of hexagonal cells decreased
      with both increasing hours of contact lens wear per day (r = -0.36, p < 0.001)
      and the duration of contact lens wear in years (r = -0.33, p < 0.001), but there
      was no significant change in endothelial cell density in contact lens wearers.
      The coefficient of variation in cell size correlated more closely with increased
      hours of contact lens wear per day (r = 0.35, p = 0.002) than with the duration
      of contact lens wear in years (r = 0.12; p = 0.31). In the functional study,
      corneal autofluorescence increased in contact lens wearers (5.13 +/- 0.71 ng/ml
      in group 1, 6.45 +/- 2.03 ng/ml in group 2 and 7.21 +/- 1.51 ng/ml in group 3,
      respectively, p < 0.001) and the mean endothelial permeability decreased in
      contact lens wearers (3.89 +/- 0.95 x10(-4)/cm in group 1, 2.71 +/- 0.73 x 10(
      4)/cm in group 2 and 2.95 +/- 0.91 x 10(-4)/cm in group 3, respectively, p =
      0.003). CONCLUSIONS: Daily wear soft contact lenses caused morphological changes
      in the corneal endothelium. With an increasing span of contact lens wear, there
      was a significantly increased variation in cell size, a decreased hexagonal cell
      percentage, an evident intercellular dark area and rosette formation. The corneal
      autofluorescence increased and the overall endothelial permeability decreased as
      a consequence of contact lens wear. Contact lens wear also caused corneal
      thinning, and the cornea became thinner with increasing duration of contact lens
      wear.

PMID- 11340392
TI  - Study on tear function abnormality in pterygium.
AB  - The purpose of this study was to determine whether there is any abnormality in
      the tear function in patients with pterygium. Eighty-four patients with pterygia
      (56 with unilateral and 28 with bilateral involvement) and 45 healthy controls
      were entered in the study. Schirmer's test, breakup time test and mucus fern test
      were applied to both eyes of the subjects. This was a prospective, comparative
      and interventional study. Tear function test results between the eyes with
      pterygium and controls were compared. They were similar in the eyes with or
      without pterygium. There were no tear function abnormalities in pterygium.

PMID- 11340393
TI  - Pterygium and dry eye.
AB  - PURPOSE: To assess the correlation between dry eye and pterygium. METHODS: Tear
      breakup time (BUT), Schirmer test with/without anesthesia and tear function index
      were evaluated in both eyes of patients with unilateral pterygium. RESULTS: Tear
      BUT, was shortened significantly in the eye with pterygium. The Schirmer test
      with anesthesia was shortened and the tear function index was decreased in the
      eye with pterygium with marginal significance. CONCLUSION: There is a correlation
      between pterygium formation and shortened BUT. Unstable tear film may contribute
      to the initiation of pterygium.

PMID- 11340394
TI  - [Les ametropies statiques du noir camerounais].
AB  - PURPOSE: We undertook this study with the aim to determine static ametropias of
      black Cameroonians as well as their clinical manifestations. It is a prospective
      study carried out in the Department of Ophthalmology of Douala General Hospital
      from January 1996 to December 1998. PATIENTS AND METHOD: During this period, all
      patients who fulfilled our criteria had a skiascopy done under cycloplegia. We
      thus examined 2,484 patients (4,968 eyes). 66.2% of them were female and 33.8%
      were male. RESULTS: In our series, hyperopia was found in 51% of the cases,
      hyperopic astigmatism in 27.5% of the cases, myopic astigmatism in 9.3% of cases,
      mixed astigmatism in 7.7% of cases and myopia in 4.5% of cases. Distribution of
      ametropias is influenced by age, not by sex or laterality. DISCUSSION AND
      CONCLUSION: Functional signs just have an indicative value; only objective
      refraction under cycloplegia can determine exactly the ametropia.

PMID- 11340395
TI  - No excess of factor V:Q506 genotype but high prevalence of anticardiolipin
      antibodies without antiendothelial cell antibodies in retinal vein occlusion in
      young patients.
AB  - Factor V:Q506 (factor V Leiden) is associated with venous thrombosis and has been
      reported to be a risk factor for retinal vein occlusion (RVO). Anticardiolipin
      antibodies (ACA), also associated with RVO, are a marker for the prothrombotic
      condition antiphospholipid syndrome, in which antiendothelial antibodies (AECA)
      are also frequently present. This study reviewed 45 younger patients <or=55 years
      old (21 with branch, 22 with central and 2 with hemispheric RVO) to examine: (1)
      the role of factor V:Q506 in the pathogenesis of RVO, and (2) the prevalence and
      titre of ACA and AECA in this group. No patient had the factor V:Q506 mutation
      indicating no increase in frequency above background. Our data suggest that
      primary screening for factor V:Q506 is not indicated for young patients with RVO
      who do not have historical evidence suggesting familial thrombophilia. Twenty
      nine patients had low-titre ACA (>10 GPL units); in 6 of these, the titre was >20
      GPL units (population reference range = 0-10 GPL units). No patient had
      antiendothelial cell reactivity. The low-titre ACA may therefore represent a non
      specific response to vascular injury.

PMID- 11340396
TI  - Expression of nitric oxide synthase during the development of RCS rat retinas.
AB  - Nitric oxide (NO) has been reported to be both neurodestructive and
      neuroprotective in the central nervous system and could possibly play an
      important role in neurodegenerative disorders. On the assumption that NO
      synthesis may influence degenerative processes in the retina, we have examined
      the development and distribution of nitric-oxide-synthase(NOS)-immunoreactive
      cells in developing Royal College of Surgeons (RCS) rat retinas, which is an
      animal model for retinal degeneration. An antibody against constitutive neuronal
      NOS was used for immunocytochemistry on RCS rat retinas from postnatal (PN) days
      3, 7, 10, 14, 35, 70 and 281 and compared with that in the normal rats of PN days
      3, 7, 10, 14, 54 and adults. Immunoreactive cells were not seen in PN 3 retinas
      but were distinctly seen in the PN 7 retina along with a plexus in the inner
      plexiform layer. In both groups (normal and RCS rats) a distinct sublayering of
      the plexus in the inner plexiform layer could be seen at PN 10, which became more
      distinct at PN 14. The immunoreactive cells were detected also in the oldest
      retina examined, which was PN 281 in the case of RCS rats. In both groups,
      certain amacrine cells, certain bipolar cells and certain horizontal cells were
      found to be immunoreactive. In conclusion, the developmental timetable of the NOS
      immunoreactivity was identical in the normal and the RCS rat retinas. The NOS
      immunoreactive cells persisted in the RCS retinas even when the retina had
      degenerated extensively. Abnormalities with the inducible isoforms of NOS cannot
      be ruled out from this study. We conclude that the chronological and qualitative
      development of the constitutive neuronal NOS immunoreactivity is normal in RCS
      rat retinas.

PMID- 11340397
TI  - Effects of isopropyl unoprostone ophthalmic solution on cultured rabbit corneal
      epithelial cells.
AB  - PURPOSE: To investigate the effects of isopropyl unoprostone (referred to as
      unoprostone) ophthalmic solution on the barrier function of cultured rabbit
      corneal epithelium grown on permeable supports. METHODS: Rabbit corneal
      epithelial cells cultured on collagen-coated filter inserts were administered one
      of the following for 30 min: unoprostone in vehicle solution (polysorbate 80),
      unoprostone in vehicle solution with a preservative (benzalkonium chloride),
      preservative only or vehicle only. For a control, no chemicals were added to the
      medium. After administration, the transepithelial electrical resistance (TER)
      measurement, a sensitive method by which to investigate the barrier function, and
      morphological observation using phase-contrast microscopy were performed before
      exposure and at 0.5, 1, 3, 6, 12, 24, 48 and 72 h after exposure. The
      transmission electron-microscopic observation was performed before and 72 h after
      exposure in all experimental conditions. RESULTS: The cells exposed to
      unoprostone with the preservative showed a significant decrease in the TER,
      although no morphological changes were observed. The corneal epithelial cells
      exposed to unoprostone without preservative, the vehicle only or the preservative
      only did not show any differences from the control group at any measurements.
      CONCLUSION: The corneal barrier function is damaged by a combined solution of
      unoprostone and preservative, but not by a single solution of unoprostone, in
      vitro.

PMID- 11340398
TI  - Posttraumatic benign pleomorphic adenoma of the lacrimal gland.
AB  - A 55-year-old man presented with a painless and slowly developing mass in the
      right superior lateral eyelid region. He had sustained periorbital blunt injury
      about 4 years previously. The mass was observed several months later in the
      persisting traumatic tumefaction region. Computed tomography showed a cystic soft
      tissue mass with central low density and peripheral enhancement over the upper
      anterior quadrant of the right orbit. Lateral orbitotomy was performed to remove
      the lesion. Histopathologic examination showed proliferation of epithelial and
      myoepithelial cells arranged in ductules and nests in the myxoid stroma. Benign
      pleomorphic adenoma of the lacrimal gland associated with traumatic tumefaction,
      as demonstrated in our patient, may be rare.

PMID- 11340399
TI  - The role of ultrasonography in the diagnosis of orbital lymphangiomas.
AB  - Orbital lymphangiomas are benign hamartomatous tumours usually diagnosed in early
      childhood. In contrast with the benign histology, these lesions have a locally
      aggressive nature. They may enlarge slowly, producing mild proptosis;
      nevertheless intrinsic haemorrhage can occur, producing a mass effect and leading
      to intractable, painful, progressive proptosis, and compressive optic neuropathy.
      A conservative approach is advisable for several reasons: complete resection is
      difficult because these lesions, unlike haemangiomas, are not encapsulated, do
      not respect anatomic boundaries, tend to penetrate into normal structures, and
      can bleed profusely during surgery. For these reasons, an early diagnosis is
      important. On this subject, ultrasonography appears to be the first-choice
      diagnostic test, because of its sensitivity and simplicity, particularly in
      childhood; therefore we recommend to always perform this test in the presence of
      orbital vascular lesion.

PMID- 11340400
TI  - Transpupillary thermotherapy for choroidal metastases.
AB  - INTRODUCTION: We report on a case with bilateral choroidal metastases derived
      from a renal cell carcinoma 13 years after nephrectomy. The treatment modality is
      discussed. METHODS: A male patient (58 years of age) presented with asymptomatic
      bilateral choroidal metastases deriving from renal cell carcinoma. The right
      kidney had been removed because of renal cell carcinoma 13 years before the
      appearance of the choroidal metastases. He had full visual acuity (20/20) and
      normal intraocular pressure in both eyes. Fundus examination showed a small tumor
      in the peripheral choroidea of his right eye and an intermediate-sized solid
      tumor in the periphery of his left eye. RESULTS: The tumor of the right eye was
      treated by TTT and the tumor of the left eye by (106)Ru plaque radiotherapy. The
      tumors showed total regression into flat chorioretinal atrophies in both eyes and
      no tumor could be found 13 moths after treatment maintaining full visual acuity
      (20/20). CONCLUSION: Asymptomatic ocular metastases can develop even many years
      after removal of the primary tumor. TTT and (106)Ru brachytherapy are useful
      treatment modalities in cases of small and intermediate-sized choroidal
      metastases.

PMID- 11340401
TI  - The incidence of central retinal artery occlusion in the district of Split,
      Croatia.

PMID- 11340402
TI  - Three-dimensional confocal microscopy of the human cornea in vivo.
AB  - This paper reviews the literature from 1990 to 2000 and evaluates the seminal
      investigations performed with the confocal microscope on the in vivo human
      cornea. Our pedagogical technique is to illustrate both the advantages and the
      problems associated with occular confocal microscopy by way of annotated
      examples. Confocal microscopy offers improved resolution and has resulted in new
      discoveries of corneal pathology at the cellular level. The ability to provide
      high-resolution, real-time images of the full thickness of the cornea gives the
      clinician and the researcher an important new tool for the investigation of the
      cornea.

PMID- 11340403
TI  - Methicillin-resistant staphylococci and ofloxacin-resistant bacteria from
      clinically healthy conjunctivas.
AB  - We evaluated the existence of methicillin (DMPPC)-resistant staphylococci and
      ofloxacin (OFLX)-resistant bacteria among preoperative patients at an eye clinic.
      Bacterial growth was studied in 194 conjunctival specimens of 125 preoperative
      patients without signs of ocular infection. Specimens were evaluated for growth
      of bacteria on Drigalski's plates, blood agar plates, or chocolate agar plates
      for 2 days at 37 degrees C. Susceptibilities of the strain to DMPPX, OFLX,
      minocycline (MINO), gentamicin (GM), erythromycin (EM), cefmenoxime (CMX),
      chloramphenicol (CP), and sulbenicillin (SBPC) were determined by the disk
      diffusion method. When DMPPC-resistant Staphylococcus aureus (MRSA) or DMPPC
      resistant coagulase- negative staphylococci (MRCNS) were isolated, the
      susceptibility of the isolated strains to vancomycin (VCM) was additionally
      examined by the disk diffusion method. Of the 125 preoperative patients (194
      eyes), 109 patients (159 eyes) had positive bacterial growth. Methicillin
      resistant Staphylococcus aureus (MRSA) were positive in 1 patient. Methicillin
      resistant coagulase-negative staphylococci (MRCNS) were positive in another
      patient. Two eyes with MRSA or MRCNS growth were treated with topical
      instillation of VCM, which was more sensitive than MINO and GM. They underwent
      the planned surgery after two subsequent tests showing negative growth. Of 120
      isolated coagulase-negative staphylococci (CNS) 8 (6.7%) were resistant to OFLX.
      OFLX-resistant CNS were sensitive to MINO, CMX, and CP, but also resistant to
      SBPC. Of 114 isolated aerobic gram-positive rods (GPR), 55 (48.2%) were resistant
      to OFLX. OFLX-resistant aerobic GPR were sensitive to MINO, CMX, SBPC, and DMPPC.
      The 157 eyes with positive bacterial growth other than MRSA were treated with
      topical instillation of sensitive antibiotics. The present findings indicate that
      DMPPC-resistant staphylococci and OFLX-resistant bacteria exist in conjunctivas
      without signs of infection.

PMID- 11340404
TI  - Mitomycin c influence on inhibition of cellular proliferation and subsequent
      synthesis of type I collagen and laminin in primary and recurrent pterygia.
AB  - The purpose was to investigate the biological effects of mitomycin C (MMC) on the
      inhibition of cellular proliferation and the subsequent synthesis of
      extracellular matrix like type I collagen (PIP) and laminin on primary and
      recurrent pterygia. The 3H-thymidine assay for cellular proliferation was
      consistent with the MMC dose and time response of both pterygia. The cellular
      inhibitory effect of MMC was greater on recurrent pterygial cells than primary
      ones. The inhibition of laminin by MMC followed the dose and time-response
      curves, with a stronger effect found in recurrent pterygial cells, but no
      significant difference between the two types concerning type I collagen
      synthesis. The inhibition of fibroblast proliferation and subsequent synthesis of
      laminin by MMC was more marked in recurrent pterygium than the primary one.

PMID- 11340405
TI  - Role of aprotinin in the management of experimental fungal keratitis.
AB  - In an experimentally induced Aspergillus fumigatus fungal keratitis in 20
      rabbits, aprotinin, an antiplasmin agent, was studied to find out its role as an
      adjuvant when given along with other established antifungal agents like natamycin
      and fluconazole. The 20 rabbits included in this study were randomly divided into
      four equal treatment groups. Once the ulcer was produced after intrastromal
      injection of 0.03 ml of A. fumigatus (5.5 x 10(4) spores/ml), different
      drugs/agents in combination were used in a randomized manner. These were
      natamycin (5%) + placebo, natamycin + aprotinin (40 IU/ml), fluconazole (0.3%) +
      placebo and fluconazole + aprotinin. The rabbits were followed up every day to
      note the signs of healing which included subsidence of corneal infiltration,
      disappearance of stromal abscess and subsidence of corneal oedema till complete
      healing. Results showed that the average healing time was 28.2, 28.4, 49.8 and
      49.0 days for natamycin + placebo, natamycin + aprotinin, fluconazole + placebo
      and fluconazole + aprotinin, respectively. It suggests that aprotinin as an
      adjuvant has no definite role in the management of fungal keratitis. The
      plasminogen activator-plasmin system which is inhibited by aprotinin may not be
      the pathway through which filamentous fungi like A. fumigatus cause tissue
      destruction.

PMID- 11340406
TI  - Human and rabbit corneal endothelial permeability after different chemical forms
      of glutathione.
AB  - This study aimed to compare the effects of reduced glutathione (GSH) with those
      of S-(1,2-dicarboxyethyl)glutathione (DCE-GS) (in rabbits and humans), and
      different concentrations of the latter (in humans), on corneal endothelial
      permeability when added to solutions bathing the isolated cornea. Inulin/dextran
      permeability was determined from stromal- to endothelial-facing surfaces of de
      epithelialized corneas. The bathing solution was modified Opeguard(R)-MA (MOMA),
      an ocular irrigating solution, to which either GSH or another intrinsic
      tripeptide, DCE-GS, was added. Paired corneas were used to compare either
      different combinations of GSH with DCE-GS (rabbit or human) or various
      concentrations of DCE-GS from 0.25 to 2.0 mM (human). Endothelial cyclic AMP
      levels were determined in cultured rabbit cells. MOMA alone resulted in
      approximately the same permeability as MOMA + 0.3 mM GSH while the use of 2 mM
      DCE-GS significantly reduced rabbit (40% maximum, p < 0.00001) and human (30%
      maximum, p < 0.01) corneal permeability. Human corneal endothelial permeability
      remained reduced through a range of concentrations of DCE-GS from 0.25 to 2.0 mM
      DCE-GS. Tissue-cultured rabbit corneal endothelium showed an increase in cyclic
      AMP after DCE-GS or GSH. DCE-GS potentially offers a viable alternative to GSH
      for inclusion in ocular irrigating or corneal preservative solutions since it
      maintains human corneal endothelial permeability at a lower, stable value
      relative to non-DCE-GS-containing solutions.

PMID- 11340407
TI  - Role of VEGF-A in endothelial phenotypic shift in human diabetic retinopathy and
      VEGF-A-induced retinopathy in monkeys.
AB  - The endothelium-specific antigen PAL-E, associated with transport vesicles in non
      barrier endothelium, is almost absent from barrier capillaries in the normal
      brain and retina. We have recently demonstrated that only leaking retinal
      capillaries in diabetic retinopathy (DR) in humans characteristically express PAL
      E. Here we investigated the relation between the expression of the PAL-E antigen
      and vascular endothelial growth factor-A (VEGF) in human post-mortem eyes of
      individuals with diabetes mellitus (DM) and in experimental VEGF-induced
      retinopathy in cynomolgus monkeys. Cryosections were cut of eyes of 41
      individuals with and 30 individuals without DM and eyes of 2 cynomolgus monkeys
      who received 4 injections of 0.5 microg VEGF in the vitreous of one eye and PBS
      in the other. The sections were stained with antibodies against VEGF, PAL-E and
      endogenous markers for microvascular leakage. Specific retinal vascular staining
      for VEGF was only observed in 10 out of the 41 cases with DM. These 10 cases also
      had marked uniform PAL-E staining and widespread vascular leakage. In contrast,
      diabetic patients without microvascular leakage and controls were negative for
      VEGF and PAL-E. Likewise, PAL-E was found only in the leaky retinal vessels of
      monkey eyes injected with VEGF. These results indicate that increased expression
      of the PAL-E antigen in retinal endothelium in conditions with microvascular
      leakage is related to VEGF and suggest that VEGF directly or indirectly induces
      PAL-E. PAL-E expression may reflect important endothelial changes involved in the
      disturbance of the blood-retina barrier in DR.

PMID- 11340408
TI  - Retinal cells produce TIMP-1 and TIMP-2 in response to cyclic mechanical
      stretching.
AB  - PURPOSE: Tissue inhibitors of metalloproteinases (TIMPs) are crucial for the
      maintenance of retinal extracellular matrix such as interphotoreceptor matrix and
      internal limiting membrane. This study is to examine whether retinal cells
      respond to mechanical stretching and produce TIMPs. METHODS: Chick retinal
      adherent cells in near confluency were exposed to mechanical stretching of the
      bottom of a 6-cm Petri dish at the maximum magnitude of 4,500 microstrain and at
      a cycle of 30 s for 72 h. TIMP-1 and TIMP-2 levels in the medium at 24, 48 and 72
      h after the beginning of stretching were measured by enzyme immunoassay, and
      their expression was examined by immunohistochemistry. RESULTS: The number of
      retinal cells during the 72-hour period of stretching did not change
      significantly both in the stretched group and in the nonstretched control group.
      Retinal cells in the stretched group produced significantly larger amounts of
      TIMP-1 and TIMP-2 at 48 h after stretching, compared with nonstretched controls
      (p = 0.0163 and p = 0.047, respectively, Mann-Whitney U test).
      Immunohistochemically, a large part of retinal cells in nonstretched Petri dishes
      was positive for glial fibrillary acidic protein, indicative of glial cells,
      while some small foci of cells were positive for neuron-specific enolase,
      indicative of neurons. Fluorescent double labeling demonstrated that both glial
      cells and neurons were positive for TIMP-1 and TIMP-2. CONCLUSION: Chick retinal
      cells, most of which were glial cells mixed with a small number of neurons,
      produced TIMP-1 and TIMP-2. Their production was enhanced by cyclic mechanical
      stretching.

PMID- 11340409
TI  - Turnover and migration of meibomian gland cells in rats' eyelids.
AB  - PURPOSE: The object of this study is to determine the velocity and migration
      course of meibomian gland cells. MATERIALS AND METHODS: Twenty-seven adult rats
      weighing about 200 g were injected intraperitoneally with a single dose of 0.5
      microCi [3H]-thymidine/g body weight. Three rats were sacrificed 1 h after
      injection and 3 rats each on days 3, 6, 9, 12, 15, 18, 21 and 28 after injection.
      The eyes and eyelids were removed in one piece, fixed in formalin, embedded in
      paraffin and cut into 5-micron-thick vertical sections along the pupillary-optic
      nerve axis. The sections were dipped in liquid autoradiographic emulsion, exposed
      for 3 weeks, and stained with HE. Meibomian glands were scanned in the lower
      eyelid of the left eye using an ocular micrometer grid. In each scan the basement
      membrane of each acinus served as a point of origin. Along the entire gland two
      parameters were noted for each nucleus with three grains or more: the distance
      from the basement membrane (Y) and grain count. RESULTS: This study demonstrates
      for the first time the exact timing and direction of meibomian gland cell
      migration. We have shown that the cells migrate from the basement membrane to the
      center of the acinus at an average rate of 0.62 +/- 0.11 micron/day. Cell
      generation time was an average of 4.1 days. CONCLUSIONS: The stem cells of
      meibomian glands lie at the circumference of each acinus. These cells migrate
      synchronously with a constant velocity towards the center of the acinus, and are
      secreted as sebaceous material.

PMID- 11340410
TI  - Variations of lacrimal fluid peroxidase activity in female and male rats.
AB  - Previous research from this laboratory showed that human lacrimal fluid
      peroxidase has cyclic variations during the menstrual cycle, correlated with
      plasma levels of 17beta-oestradiol. In the present investigation, variations of
      enzyme activity and total protein content during the oestrous cycle of young
      adult female rats are analysed. Effects from circadian rhythm and a gender
      related influence are also examined. In female rats, as in women, lacrimal fluid
      peroxidase activity shows cyclic variations; in fact, it significantly (p < 0.05)
      changes during the different phases of the oestrous cycle. In contrast, in males
      such variations do not occur. Thus, we suggest that gender seems to exert a
      significant influence on the secretion of this specific tear protein, probably by
      a direct effect of oestrogens.

PMID- 11340411
TI  - Effects of check size on visual cortex activation studied by functional magnetic
      resonance imaging.
AB  - We studied functional magnetic resonance imaging (fMRI) of visual cortex during
      checkerboard visual stimulation with three standard check sizes to examine
      whether activation in the visual cortex varied among these sizes. We acquired
      fMRI at 1.5 T in 8 normal subjects, each receiving the best refractive
      correction. Each subject underwent an experiment consisting of four conditions:
      black and white checkerboards with three check sizes (0.25-, 0.5-, and 1.0
      degree) flickering at 8 Hz, and a black screen. SPM96 was used for a group data
      analysis with a random effects model after each of the subject's data was motion
      corrected and spatially normalized to a standard brain. The activation in the
      visual cortex showed the greatest signal changes with the 0.5-degree check among
      the three check sizes. When standard check sizes are used to stimulate visual
      cortex in fMRI experiments, our results suggest that 0.5-degree checks flickering
      at 8 Hz produce the most vigorous activation in visual cortex.

PMID- 11340412
TI  - Journal policies on conflict of interest: if this is the therapy, what's the
      disease?

PMID- 11340413
TI  - Stressful life events and skin diseases: disentangling evidence from myth.
AB  - The possibility of a causal influence of emotional stress, especially of
      stressful life events, on the course of various skin diseases has long been
      postulated. Clinical wisdom and experience, as well as many anecdotal
      observations and uncontrolled case series, support this opinion. We reviewed the
      available evidence on the role of stressful life events in triggering or
      exacerbating skin diseases. The role of stressful events in vitiligo, lichen
      planus, acne, pemphigus and seborrhoeic dermatitis was either controversial or
      insufficiently explored. The role of stressful events in psoriasis, alopecia
      areata, atopic dermatitis and urticaria was apparently clearer. However, only a
      few studies met acceptable methodological standards for stress measurement. Also,
      few studies considered common potential confounding factors (e.g. age, duration
      of illness, familial factors), and no study controlled adequately for the
      influence of other crucial factors (e.g. discontinuation of treatment, seasonal
      effects). Adding that the large majority of studies were retrospective, it seems
      wise to conclude that only preliminary evidence has been published so far on the
      role of stressful life events in bringing on or worsening any dermatological
      disease. Further research is mandatory, either in the form of prospective studies
      or, more feasibly, of well-designed case-control studies with adequate
      statistical power. Future studies should also pay more attention to protective as
      well as vulnerability factors in stressful events. Further, it would be important
      to investigate other sources of psychological stress, such as chronic stress and
      everyday stress. Measuring stress appraisal, although difficult, would also be
      important.

PMID- 11340414
TI  - Over-the-counter drug use in gymnasiums: an underrecognized substance abuse
      problem?
AB  - OBJECTIVE: Many individuals, attempting to gain muscle or lose fat, use 'dietary
      supplements'. Though widely available over the counter or by mail order in
      America and Europe, some of these 'supplements' are actually potent drugs such as
      androstenedione and ephedrine. We sought to estimate the prevalence of these
      forms of drug use in American gymnasiums. METHODS: We distributed anonymous
      questionnaires to 511 clients entering five gymnasiums, asking about use of both
      supplements and anabolic steroids. RESULTS: Among men, 18% reported use of
      androstenedione and/or other adrenal hormones, 25% reported ephedrine use, and 5%
      reported anabolic steroid use within the last 3 years; among women these rates
      were 3, 13 and 0%. Extrapolating from these figures to the United States as a
      whole, we estimated that possibly 1.5 million American gymnasium clients have
      used adrenal hormones and 2.8 million have used ephedrine within the last 3
      years. CONCLUSIONS: Millions of men and women are currently using potent drugs,
      widely sold over the counter as 'supplements', despite their known adverse
      effects, unknown long-term risks, and possible potential for causing abuse or
      dependence.

PMID- 11340415
TI  - Diagnostic Accuracy in the First 5 min of a Psychiatric Interview. Impact of the
      information given by patients.
AB  - BACKGROUND: There is little if any research on the explicit contents delivered by
      patients in the first minutes of a psychiatric interview. METHODS: In order to
      study the impact of the first minutes of a psychiatric interview on final
      diagnosis, we gathered information from the speech during the first 5 min in 162
      new psychiatric patients with a checklist including symptoms extracted from the
      SCAN interview. RESULTS: The area reported most frequently was life events
      (51.2%). The average of psychiatric symptoms cited was 2.3. An initial suspected
      diagnosis was done in 126 patients, and in 73 patients (57.9% of those with a
      suspected diagnosis, 45.1% of the total sample) the initial diagnosis was
      coincident with the final diagnosis. The initial clinical impression was more
      accurate in adjustment and 'neurotic' disorders, and less in mood disorders.
      Those patients who cited more symptoms received a less accurate initial
      diagnosis. CONCLUSION: Psychiatric patients spontaneously report a low number of
      symptoms. The accuracy of psychiatric diagnosis in the first minutes of an
      interview is unacceptably low. However, the role of short psychiatric
      interviewing as a screening method deserves to be further investigated.

PMID- 11340416
TI  - Psychiatric symptoms associated with scleroderma.
AB  - BACKGROUND: The prevalence of psychiatric symptoms and hostility factors in
      patients with scleroderma, although a matter of clinical interest, it is rather
      poorly studied. METHODS: Thirty female patients with scleroderma were
      investigated. Thirty-three healthy women were used as a comparison group. The
      applied psychometric instruments were the Hostility and Direction of Hostility
      Questionnaire (HDHQ), the Delusions Symptoms States Inventory/states of Anxiety
      and Depression (DSSI/sAD) and the Symptom Check List-90R (SCL-90R). RESULTS: The
      scleroderma patients reported significantly increased depression and anxiety,
      somatization, interpersonal sensitivity and obsessive-compulsiveness. Paranoid
      ideation and psychotic symptoms scores were also increased. On hostility, they
      presented significantly higher scores predominantly on guilt. CONCLUSIONS:
      Psychiatric symptomatology in the form of anxiety, depression, obsessive
      compulsiveness, somatization and feelings of guilt were reported by the majority
      of the patients with scleroderma.

PMID- 11340417
TI  - Efficacy of 'functional relaxation' in comparison to terbutaline and a 'placebo
      relaxation' method in patients with acute asthma. A randomized, prospective,
      placebo-controlled, crossover experimental investigation.
AB  - BACKGROUND: 'Functional relaxation' (FR) according to Marianne Fuchs is a body
      oriented psychotherapy that involves teaching the patient a type of relaxation
      techniques aimed at maintaining equilibrium of the nervous system. METHODS: In
      order to determine whether the practice of elementary parts of this therapy has
      an immediate beneficial effect on pulmonary function, a randomized, single-blind,
      prospective crossover study was done with 21 asthmatics with acute
      bronchoconstriction. On 3 consecutive days they were given either (1) a 5-min
      verbal standard instruction in elementary exercises of FR (eFR), which they were
      to practice during subsequent bodyplethysmographic measurement or (2) inhalative
      terbutaline (IT), a beta(2)-sympathomimetic drug, or (3) an unspecific 'placebo
      relaxation' technique (PRT), so that all subjects tried all 3 treatments in
      random order. Spirometric variables were assessed. RESULTS: There was a
      significant decrease in specific airway resistance with eFR, which, though not as
      pronounced as with IT, was significantly greater than with PRT. This study shows
      that clinically relevant effects can be achieved for patients with asthma through
      mind-body interaction, which can be triggered by reproducible procedures.
      CONCLUSION: Further development of the FR approach could lead to a
      nonpharmacological and effective supplementary treatment for asthma, which is in
      high demand by many patients.

PMID- 11340418
TI  - Obstetrical and neonatal outcome following clonazepam use during pregnancy: a
      case series.
AB  - BACKGROUND: Given the high prevalence of panic disorder in women, treatment
      decisions are frequently made regarding the use of anti-panic medications during
      the childbearing years and during pregnancy. The objective of this case series
      was to evaluate obstetric and neonatal outcome associated with treatment with
      clonazepam during pregnancy. METHODS: Subjects were 38 women with histories of
      panic disorder who used clonazepam during pregnancy. Information regarding the
      amount and duration of clonazepam use during pregnancy was obtained. Obstetrical
      records describing pregnancy, labor and delivery and infant Apgar scores were
      obtained for all subjects. Neonatal nursery records were obtained for 27
      subjects. RESULTS: Maternal outcome assessed by obstetrical records and acute
      neonatal outcome assessed by Apgar scores were positive. Based on neonatal
      records, there were no cases of orofacial anomalies, neonatal apnea,
      benzodiazepine withdrawal syndromes, or temperature or other autonomic
      dysregulation. In 2 infants born to the same mother, use of clonazepam and
      imipramine at the time of delivery was associated with transient neonatal
      distress. CONCLUSION: Clonazepam use during pregnancy did not appear to be
      directly related to any obstetric complications during pregnancy, labor, or
      delivery. There was no evidence of neonatal toxicity or withdrawal syndromes in
      babies born to mothers who took clonazepam during pregnancy. Absence of serious
      maternal or neonatal compromise following clonazepam use during pregnancy in
      these mothers and infants is somewhat reassuring. One case of hypotonia and 1
      case of respiratory distress in babies who were exposed to clonazepam in
      combination with imipramine at the time of delivery may suggest that
      coadministration of benzodiazepines with other psychotropic medications may
      require close neonatal observation.

PMID- 11340420
TI  - Female depression and menopause.

PMID- 11340419
TI  - Family and past history of mental illness as predisposing factors in post
      traumatic stress disorder.
AB  - BACKGROUND: Family studies of post-traumatic stress disorder (PTSD) have given
      inconsistent results to date. Identifying predisposing factors in PTSD compared
      to anxiety disorders may help to clarify the classification of PTSD as a
      diagnostic entity. METHOD: Retrospective case note study of 87 PTSD patients who
      participated in an RCT, and 51 PTSD patients and 87 agoraphobics treated
      routinely in outpatients. RESULTS: Compared to agoraphobics, PTSD patients had
      significantly less family history of anxiety disorder but not mental illness in
      general. They also had significantly less personal history of mental illness
      prior to the index episode. CONCLUSIONS: Trauma precipitated PTSD in subjects who
      had significantly fewer premorbid predisposing factors than did agoraphobics.
      Such factors may predispose agoraphobics to become psychiatrically ill after more
      minor trauma. Research is needed to systematically compare the events which
      precipitate PTSD as opposed to agoraphobia and other anxiety disorders.

PMID- 11340433
TI  - [Breast calcification: when to do biopsy?].

PMID- 11340422
TI  - [Obesity: can we to improve?].

PMID- 11340432
TI  - [Can the inguinal hernia became a dilemma].

PMID- 11340434
TI  - [Why my asthmatic patient does not stabilize despite of appropriate medication?].

PMID- 11340435
TI  - [May the physician refuse to allow the discharge requested by his patient?].

PMID- 11340436
TI  - [What surgical procedures must be adopted in the treatment of bronchopneumonia
      with pleural effusion in children?].

PMID- 11340445
TI  - [Duty feeling].

PMID- 11340444
TI  - [Hormonal replacement therapy in women with clinical disorders].

PMID- 11340447
TI  - [Snake bites].

PMID- 11340448
TI  - [Absent or reversed diastole to umbilical arteries doppler flow velocities].

PMID- 11340449
TI  - [Vesical endometriosis: diagnosis and therapeutic aspects].

PMID- 11340450
TI  - [Complement system: activation, regulation and congenita and acquired
      deficiency].

PMID- 11340451
TI  - [Assessment of auditory behaviour and neuropsychomotor development of low weight
      infants].
AB  - PURPOSES AND METHODS: The aims of this study were: to detect moderate to profound
      hearing loss in high risk infants for deafness, to follow up their auditory
      development (localization of the sound source- Hear Kit - Downs, 1984); and their
      neuropsychomotor development during the two first years of life. All subjects
      were submitted to cerebral ultra sound assessment. RESULTS: An infant with a
      suspected hearing loss was identified and nine infants presented neuropsychomotor
      development delay. In a transversal analysis of the hearing assessment data it
      was verified that infants in this study presented different response than the
      referred in the American literature. CONCLUSIONS: It was concluded that 5% of the
      infants were delayed in localizing the sound source. Medical peech and hearing
      follow up during the two first years of life of high risk infants for deafness is
      important and advisable.

PMID- 11340452
TI  - [Use of transcranial Doppler in monitoring cerebral vasospasm secondary to
      subarachnoid hemorrhage].
AB  - Cerebral vasospasm accounts for an increased morbidity and mortality in patients
      with spontaneous subarachnoid hemorrhage (SAH). Its early and non invasive
      detection by transcranial Doppler (TCD) may contribute to a better prognosis in
      such cases. PURPOSE: To discuss the use of transcranial Doppler (TCD) in the
      detection of cerebral vasospasm secondary cerebral to spontaneous subarachnoid
      hemorrhage (SAH). METHODS: We analyzed the flow velocities registered by TCD in
      intracranial arteries in 31 patients with SAH, performed sequentially, associated
      with neurological examinations. All patients (except one) had intracranial
      aneurysms. RESULTS: Clinical vasospasm was found in 11 patients (36,6% from the
      total), with correspondent sonographic vasospasm present in 9 cases (82%). In 3
      cases (33.3%) the flow velocity alterations preceded the clinical symptoms.
      Between the 20 asymptomatic patients, 15 (75%) had normal flow velocity, with
      evidence of sonographic vasospasm without clinical repercussion in 5 (25%). The
      index of false negatives in the correlation between clinical examination and TCD
      (symptomatic vasospasm with normal flow velocity records) was 18%. However, there
      was correspondence between clinical and ultrasonographic findings in 26 of the 31
      patients (83.8%). The average flow velocity values in the various arteries and
      its interpretation for each subgroup are discussed with further details.
      CONCLUSION: TCD is a valuable auxiliary method in the detection of cerebral
      vasospasm (even pre-symptomatic) secondary to SAH, allowing a more precocious
      therapeutic intervention. Our results are similar to those described in the
      literature.

PMID- 11340453
TI  - [Use of the CAGE questionnaire for detecting alcohol use disorders in the
      emergency room].
AB  - BACKGROUND: Alcoholism is seldom detected among emergency room outpatients, which
      is attributed to the non-adoption of diagnostic routines, to the difficulty of
      doing a special anamnesis for diagnosing alcoholism, and to the lack of
      sensitivity and specificity of the laboratory tests. This study has the purpose
      to determine whether the CAGE assay (composed by 4 questions of easy
      memorization) is able to supply this difficulty in detecting alcoholism. MATERIAL
      AND METHODS: We did a transversal study with consecutive sampling among
      outpatients of the Internal Medicine Department at Cajuru University Hospital
      emergency room. They were submitted to a standardized interview constituted by
      the CAGE and the CIDI assays (Composite International Diagnostic Interview,
      "demographics" and "disorders resulting from the use of alcohol" sections). From
      the sample obtained (n=374), we correlated the prevalence of alcoholism according
      to both questionnaires, considering the CIDI (DSM-IV criteria) to be the gold
      standard. RESULTS: The prevalence of alcohol dependence according to the DSM-IV
      criteria was 15.77%. We verified that the CAGE has 84.74% of sensitivity and
      73.33% of specificity, with a cut point of 2 positive responses. CONCLUSIONS: We
      concluded that the CAGE is an instrument of easy application and good sensitivity
      and specificity when used at the emergency room, being able to supply the
      difficulties of alcoholism detection. We suggest that the CAGE be adapted as a
      routine at emergency rooms, increasing the alcoholism detection rate.

PMID- 11340454
TI  - [Study of preoperative risk factors for bacteriobilia in patients with acute
      calculosis cholecystitis].
AB  - OBJECTIVE: to determine an association between the preoperative clinical status
      and the result of bile and gallbladder wall cultures. MATERIAL AND METHODS: 28
      variables regarding history, physical examination and labatorial assessment in 38
      patients with acute calculosis cholecystitis submitted to urgency surgery were
      prospectively studied during a 19-month period, between November 1995 and May
      1997. Cultures for aerobic and anaerobic agents from both the gallbladder wall
      and the bile were performed, in three different culture media (BACTEC 9240, BHI
      and HEMOBAC). RESULTS: bacteria were isolated in at least one culture medium, in
      68.2% of the patients. At univariate analysis, five preoperative factors were
      identified as predictors of bactibilia: over 55 years of age, a greater than 0.4
      degrees C difference in the axillary-rectal temperature, a greater than 12.000
      cels/m3 blood leukocyte count, a greater than 75% neutrophil percentage and a
      greater than 4% rod neutrophil percentage. Owing to the small sample size,
      statistical significance of the series could not be noted by logistic regression,
      although a trend to preoperative determination could be observed in 98% of the
      subjects with positive culture, by means of the model based on age and percentage
      of rod neutrophil. By analyzing predictive factors jointly, it was noted that
      patients with more than one predictive factor have a significantly greater
      possibility to yielding positive culture when compared to those with up to one
      predictive factor for bactibilia. CONCLUSIONS: We concluded that, in patients
      with acute calculosis cholecystitis, bactibilia may be predicted yet at the
      preoperative period, by using simple and easily obtained data.

PMID- 11340455
TI  - [Association between race and incidence of end-stage renal disease secondary to
      glomerulonephritis: influence of the histologic type and presence of arterial
      hypertension].
AB  - OBJECTIVE: To assess, retrospectively, the association between race and incidence
      of end-stage renal disease (ESRD) in patients with glomerulonephritis in a
      University Hospital of Bahia, Brazil. METHODS: The sample was comprised of 79
      patients with focal segmental glomerulosclerosis (FSG), 50 with
      membranoproliferative glomerulonephritis (MPGN) and 49 with other types of
      glomerulonephritis (OTGN), followed-up between 1970 and 1996 for at least 6
      months. It was not included patients with acute glomerulonephritis, minimal
      change disease, crescentic glomerulonephritis, connective tissue diseases or
      patients with serum creatinine level greater than or equal to 4.0 mg/dl. The
      patients were classified according to race as caucasian (white), mulatto or
      negro. For patients older than 18 yr, not taking antihypertensives drugs,
      hypertension was defined as a mean of three blood pressure measurements greater
      than or equal to 140 mmHg for systolic or 90 mmHg for diastolic; for ages </= 18
      years. The definition was based on criteria recommended by the Task Force on
      Blood Pressure in Children. RESULTS: In the normotensive group, the incidence of
      ESRD was 72% lower in mulattos and negroes (relative risk (RR)=0.28; 95%
      confidence interval (CI)=0.11-0.67). In the group with hypertension, the
      direction of association between race and ESRD was opposite to that observed in
      the normotensive group (RR=1.49; 95% CI= 0.68-4.34). The modification in the RR
      depending on the presence or the absence of hypertension was statistically
      significant (p=0.01). In the normotensive group the RR shifted toward the null
      hypothesis after the inclusion of histologic type in the Cox model. CONCLUSIONS:
      Among normotensive patients with glomerulonephritis the incidence of ESRD was
      greater in caucasians (whites) than in negroes or mulattoes. By contrast among
      hypertensive patients there was a trend for a higher risk of ESRD in negroes. The
      study suggests that hypertension and the histologic type of glomerulonephritis
      influence the association between race and ESRD.

PMID- 11340456
TI  - Is the relationship between population density and body size consistent across
      independent studies? A meta-analytical approach.
AB  - The Energetic Equivalence Rule (EER) is a controversial issue in ecology. This
      rule states that the amount of energy that each species uses per unit of area is
      independent of its body size. Here, we perform a meta-analytical procedure to
      combine and compare the slopes of population density and body size relationships
      across independent studies of mammals and birds. We then compared a distribution
      of 50,000 bootstrap combined slopes with the expected slope (b = -0.75) under the
      EER. The combined slopes obtained for mammals and birds separately were -0.755
      and -0.321, respectively. The homogeneity hypothesis (i. e. within studies the
      slopes differ by no more than would be expected due sampling variation) was
      rejected in both cases. So, EER cannot be supported since the use of an exponent
      of -0.75 is, in fact, an oversimplification. Significant heterogeneity of slopes
      within each group (mammals and birds) is an indicator of inferential problems
      related with variation in body size, spatial scale, the regression model adopted
      and phylogenetic relationships among species. So, we consider that questions
      regarding the estimation and validity of slopes is the next challenge of density
      body size relationship studies.

PMID- 11340457
TI  - Natural and human impacts on invertebrate communities in Brazilian caves.
AB  - Species richness, abundance, distribution and similarity between cave
      invertebrate communities were compared among seven caves located in the Peruacu
      River valley, north of Minas Gerais State, Brazil. Such comparisons aimed to
      determinate the degree of biological complexity in the sampled caves, calculated
      by the "Index of Biological Complexity in Caves", presented in this manuscript.
      The presence of potential or real impacts on the cave fauna was also
      investigated. A total of 1,468 individuals belonging to 57 families of: Acarina,
      Pseudoscorpionida, Araneida, Opilionida, Amblypygi, Isopoda, Geophilomorpha,
      Scutigeromorpha, Spirostreptida, Coleoptera, Collembola, Diptera, Dictyoptera,
      Ephemeroptera, Ensifera, Heteroptera, Hymenoptera, Lepidoptera, Plecoptera,
      Psocoptera, and Trichoptera was collected. Caves with higher resource
      availability (as those hidrologicaly actives) had a higher biological complexity
      than those with less resource. There are two types of impacts that occur in the
      area: the natural (geological) and the anthropic, as intense "stepping" and
      visitation or use of cave entrances as cattle shelters. There are caves with
      different preservation degrees in the area, with invertebrate communities in
      varied complexity states. The communities of these caves undoubtedly deserve
      care, since the area is extremely important in the Brazilian biospeleological
      context.

PMID- 11340458
TI  - The water level influence on biomass of Echinochloa polystachya (Poaceae) in the
      Jurumirim Reservoir (Sao Paulo, Brazil).
AB  - In the Paranapanema River mouth, Jurumirim Reservoir (23 degrees 27'-23 degrees
      29'S and 48 degrees 39'-48 degrees 36'W, SP, Brazil), the biomass of E.
      polystachya was monthly determined with eight quadrats of 0.25 m2 from August
      1993 to July 1994. The seasonal variation in biomass was unimodal, with greater
      biomass from November 1993 to April 1994. The average biomass was 1,933.7 +/-
      479.5 gDW.m-2, with a variation along the year from 1,149.0 to 2,755.9 gDW.m-2.
      The annual variation of aerial green biomass, aerial and aquatic detritus suggest
      that the main growth period of E. polystachya was from December 1993 to May 1994,
      with peak between February to March 1994. The data indicate that this macrophyte
      is adapted to water level variation.

PMID- 11340459
TI  - Trophic morphology of five benthic-feeding fish species of a tropical floodplain.
AB  - This study describes the morphology of the digestive apparatus and the size and
      organic content of the ingested food of five species of benthic-feeding fishes
      (Prochilodus lineatus, Steindachnerina insculpta, Loricariichthys platymetopon,
      Trachydoras paraguayensis e Iheringichthys labrosus). The samples were taken in
      the floodplain of the up Parana River in February and August 1991. The results
      suggested that these species have different mouth, teeth, gill rakers, stomach
      and intestine length. These morphologic characteristics were related with the
      type, size and nutritional quality of the food ingested. Although these species
      feed on the bottom, the morphologic divergences probably explain the differences
      in diet.

PMID- 11340460
TI  - The soil seed bank during Atlantic Forest regeneration in Southeast Brazil.
AB  - A survey was conducted to determine the density and species composition of viable
      seeds buried in four stands of a tropical montane forest at Parque Estadual
      Intervales, Brazil. The objective was to understand: (1) how numbers and
      composition of the soil seed bank change as the forest regrows, and (2) how such
      changes affect the species available for regeneration if forests of different
      ages are cut down. In each forest stand (5, 18, 27-yr-old and a mature forest),
      57 soil samples were collected (0-2.5 and 2.5-5 cm deep). Viable seed density of
      herbaceous species ranged between 11,003 seeds. m-2 (5-yr-old vegetation) and 482
      (mature forest), and between 25 (5-yr-old vegetation) and 389 seeds. m-2 (mature
      forest) for woody plant species in the 0-5 cm soil layer, suggesting a decrease
      in seed stocks in the course of forest regeneration. Seeds buried in the 0-2.5 cm
      soil layer represented between 56.9% and 67.4% of all viable seeds. Most of the
      viable seeds belonged to weeds of Asteraceae, Poaceae, Malvaceae and Solanaceae.
      The results provide evidence that, in forests of different ages, the soil does
      not store seeds of the same key ecological groups involved in the regeneration of
      Atlantic forest. Allochthonous seeds from remaining patches of forest, as well as
      their vertebrate dispersers, are needed for forest regeneration since the soil
      seed bank does not store large seeds of shade-tolerant species.

PMID- 11340461
TI  - Abundance of cladocerans in the littoral regions of two environments of the Upper
      Parana River floodplain, Mato Grosso do Sul, Brazil.
AB  - The abundance of cladocerans recorded in plankton samples from the littoral
      regions of two environments (Baia River and Guarana lake), the Upper Parana River
      floodplain and some limnological variables important in controlling their
      abundance were investigated at three sites in the lake and two in the river, from
      March/93 to January/94. Abundance was highest in the lake, chiefly during high
      water. Bosminidae dominated in both environments and hydrological periods (high
      and low water). Chydoridae were more important in the lake, and Sididae in the
      river. A higher number of Pearson's correlations significative (p < 0.03) between
      the densities of the ten most important species and the limnological variables
      was observed in the river. This suggests that limnological variables are more
      important in controlling the abundance of cladocerans in the river. On the other
      hand, in the lake their abundance was probably associated with the physical
      structure of the environment, the abundance of aquatic macrophytes, and biotic
      relationships such as competition and predation.

PMID- 11340462
TI  - Gastrointestinal parasites and prey items from a mass stranding of false killer
      whales, Pseudorca crassidens, in Rio Grande do Sul, Southern Brazil.
AB  - The gastrointestinal tract of 14 false killer whales, 6 males and 8 females,
      stranded in June 1995 in southern Brazil, with total standard lengths from 338 to
      507 cm, were analysed for endoparasites and food items. A pregnant female had a
      male foetus of 77.5 cm. Parasites were found in all 14 false killer whales. The
      nematode Anisakis simplex (Rudolphi, 1809) was found in the stomach of 57% of the
      animals and the acanthocephalan Bolbosoma capitatum (Linstow, 1889) Porta, 1908
      was present in the intestine of all specimens and showed densities up to 600 m-1.
      An unidentified cestode (Tethrabothridae) was found also in the intestines of 14%
      of the individuals. The high infections of B. capitatum and A. simplex were not
      directly related with the cause of death. In the stomachs of four females, beaks
      of at least eight specimens of the oceanic and epipelagic species Ommastrephes
      bartramii (Lesueur, 1821) were found, with mantle lengths ranging from 189.8 to
      360.9 mm. The distribution of O. bartramii in the coast of Rio Grande do Sul is
      consistent with false killer whales feeding in continental shelf waters.

PMID- 11340463
TI  - Pollen spectrum of honey of "urucu" bee (Melipona scutellaris Latreille, 1811).
AB  - In spite of the importance of the "urucu" bee as honey producer of excellent
      quality, as well, potential pollinator both in agricultural and natural
      ecosystems, mainly in North-eastern Brazil, just some information is found in
      literature about sources that such bees utilize to collect nectar and pollen. The
      identification of the plants visited by Melipona scutellaris was accomplished
      with base on the analysis of pollen types found in the honey samples collected
      every two months, from March 1997 to February 1998, in 15 colonies located in
      Catu, State of Bahia, Brazil (12 degrees 21'00"S, 38 degrees 22'40"W, 76 m of
      altitude). Qualitative and quantitative analysis of the pollen types were carried
      out determining the percentage and occurrence classes. Twenty-eight pollen types
      were found, being considered dominant pollen, the Eucalyptus spp. and Psidium sp.
      types and secondary pollen, Bauhinia sp., Caesalpinia sp. and Mimosa verrucata
      types. It was verified dominant pollen of Eucalyptus spp. in honeys produced in
      November/December 1997 and January/February 1998. The families Caesalpiniaceae
      (14%), Mimosaceae (25%) and Myrtaceae (56%) were the most represented in the
      pollen spectrum.

PMID- 11340464
TI  - Epithelial gill cells in the armored catfish, Hypostomus cf. plecostomus
      (Loricariidae).
AB  - Epithelial gill cell morphology and distribution were investigated in the armored
      catfish, Hypostomus cf. plecostomus, which lives in soft ion-poor Brazilian
      freshwaters. Pavement cells are the most abundant type of cell on both filament
      and lamellar epithelia and there are a great number of mucous and chloride cells
      between them. Mucous cells are almost covered by adjacent pavement cells and have
      large packed granules showing electrondense differences. No mucous cells were
      found on the lamellar epithelium. Chloride cell were distributed throughout both
      epithelia and usually have large apical surface facing the external medium and
      may exhibit short and sparsely distributed microvilli. The presence of chloride
      cells on the lamellar epithelium may be an adaptation to low ion concentrations
      in the water, allowing for improved ion-transport capacity of the gill. The large
      size of these cells increases the water-blood barrier and may affect the
      transference of respiratory gases. However, the negative effect on the
      respiratory process may be minimized by this species' ability to resort to
      atmospheric air to fulfill its oxygen requirements.

PMID- 11340465
TI  - Reproduction and food habits of the lined seahorse, Hippocampus erectus
      (Teleostei: Syngnathidae) of Chesapeake Bay, Virginia.
AB  - The reproductive and feeding biology of the lined seahorse, Hippocampus erectus,
      was studied in Chesapeake Bay. Seahorses are monogamous, and males incubate the
      eggs received from females in a closed brood pouch (= marsupium). Females do not
      play any parental care after mating. Total sex ratio and the operational sex
      ratio was strongly skewed toward females. Males and females had similar number of
      eggs/embryos and hydrated oocytes, respectively. The number of eggs/embryos found
      in the male brood pouch varied from 97 to 1,552 (fish from 80 to 126 mm TL),
      whereas the number of hydrated oocytes in female varied from 90 to 1,313 (fish
      from 60 to 123 mm TL). Both, the number of eggs/embryos and hydrated oocytes were
      better linearly correlated to total weight than to total length. The small snout
      and mouth size limits the feeding of the lined seahorse to small prey size.
      Amphypods were the predominant food items found in the guts, especially Ampithoe
      longimana, Gammarus mucronatus, and Caprella penantis. The lined seahorse is not
      abundant in Chesapeake Bay, but keeps a breeding population which is probably
      brought inside the bay by currents on drifting vegetation. Chances to find a
      partner may be difficult because of its low abundance, due to turbid waters, and
      its sedentary behavior.

PMID- 11340466
TI  - Evidence of terrestrial feeding in the arboreal lizard Enyalius bilineatus
      (Sauria, Polychrotidae) of south-eastern Brazil.
AB  - The diet of the arboreal lizard E. bilineatus was assessed based on analysis of
      gut contents of specimens collected in the remnants of the Atlantic rainforest in
      Espirito Santo State, south-eastern Brazil. Stomachs of the lizards examined (SVL
      = 57.0-85.0 mm) contained nine arthropod orders. E. bilineatus utilizes a broad
      range of arthopodan prey type and sizes, and can be considered an arthropod
      generalist, which uses a sit-and-wait foraging strategy. Orthoptera represented
      the most important food item, followed by Dictyoptera and Hymenoptera. Hemiptera,
      Homoptera, Lepidoptera (larvae), Coleoptera, Araneae, and Diplopoda constituted
      the remainder of food items. The presence of Diplopoda, which are not generally
      found on tree trunks, provides particularly strong evidence the E. bilineatus
      forages in leaf litter on the ground.

PMID- 11340467
TI  - Dufour glands in the hymenopterans (Apidae, Formicidae, Vespidae): a review.
AB  - Associated to the sting apparatus of the aculeate hymenopterans is found the
      poison gland, originated from the glands associated to the ovipositor of the non
      aculeate hymenopterans and the less derived Dufour gland, homologue of the
      coletterial gland of other insects, and found in all hymenopteran females. The
      Dufour gland functions is mostly uncertain in hymenopterans but in ants it is
      involved with communication and defense and in non social bees with the nest
      building and protection. In wasps possibly with kin-recognition. Differences in
      morphology and chemical composition of the gland secretion were observed among
      species, in the same species, between the castes in the social species and among
      individual of the same caste playing different tasks or belonging to different
      nest. Its original function of egg-protective substance producing, or favoring
      the oviposition, appear to have been replaced or complemented in hymenopterans by
      the production of semiochemicals with function in communication.

PMID- 11340468
TI  - Sandflies (Diptera: Psychodidae) of the Amazonia of Maranhao. V. Seasonal
      occurrence in ancient colonization area and endemic for cutaneous leishmaniasis.
AB  - In this paper, the seasonal abundance of 25 sandfly species (1 of the Brumptomyia
      genus and 24 of the Lutzomyia genus) found at P1V5, municipal district of
      Buriticupu, Maranhao State, is discussed. The capture was carried out from 18:00
      P.M. to 6:00 A.M., once a month, from January to December 1996. CDC light traps
      were set up in the forest, in the peri and intradomicile environments. Five
      species were only found in the rainy season (January to June), being represented
      by one or two individuals; eight species occurred only in the dry season (July to
      December) and eleven species appeared in both seasons. The most frequent species
      in the dry period were: L. whitmani (26.3%), L. serrana (23%), L. choti (22.8%),
      L. evandroi (7.5%), L. longipalpis (5.8%), L. termitophila (3.3%), L. shannoni
      (3%) and L. migonei (2.5%). In the rainy season, L. whitmani was the prevailing
      species (74%), followed by L. termitophila (4%), L. umbratilis (3.4%), L. serrana
      (2.8%), L. evandroi (2,8%) and L. claustrei (2.4%). L. whitmani was thought to be
      an annual species, occurring in the entire year of study. The others species,
      with exception to L. serrana and L. evandroi, showed a seasonal, punctual or
      peripheric pattern.

PMID- 11340469
TI  - Growth of the annual fish Cynopoecilus melanotaenia (Regan, 1912) based in a
      temporary water body population in Rio Grande do Sul State, Brazil
      (Cyprinodontiformes, Rivulidae).
AB  - The growth of the annual fish Cynopoecilus melanotaenia was studied in its
      natural environment, in order to obtain information about its biology. A total of
      797 specimens of C. melanotaenia were collected on a monthly basis between April
      1994 and March 1995 in a temporary water body, located in Rio Grande do Sul
      State, Brazil. The growth curve in total length suggests, to both sexes, a fast
      initial growth. Males present a smaller growth rate than females, but they attain
      a higher average maximum length than the females.

PMID- 11340470
TI  - Characterization of the larval stages of Alphitobius diaperinus (Panzer)
      (Coleoptera: Tenebrionidae) using head capsule width.
AB  - The mean width (n = 5) of the cephalic capsule instar of Alphitobius diaperinus
      was determined. The larvae were reared at 27 degrees C (+/- 0.1 degrees C). The
      result showed that A. diaperinus has eight larval instars. The head capsule of
      the 1st instar larvae measured x = 0.228 (SD = 0.0192) and the last instar larval
      measured x = 1.339 (SD = 0.0436). The developmental rate, determined by Dyar
      Hutchinson's rule, was 1.29. These data may be useful for studies on phenology
      and age structure of A. diaperinus in the field.

PMID- 11340471
TI  - Ultrastructure of ovarian follicular epithelium of the Amazonian fish
      Pseudotylosurus microps (Teleostei: Belonidae): morphological and histochemical
      characterization of the intercellular deposits.
AB  - The present paper reports the presence of great quantities of electrondense
      intercellular material in the follicular epithelium of P. microps. The material
      apparently is uptaken from circulation and enter the follicle through the
      intercellular spaces accumulating in the epithelial median-apical intercellular
      spaces and in perioocytic space. The accumulation starts in the early growth of
      the primary oocyte and proceed until vitellogenesis. The possible chemical nature
      and function of the deposits are discussed.

PMID- 11340472
TI  - Application of deterministic model of isothermals for population dynamics of
      Synthesiomyia nudiseta (Diptera, Muscidae).
AB  - The isothermal deterministic model adherence was studied to evaluate the
      population dynamic of Synthesiomyia nudiseta (Diptera, Muscidae). The linear form
      of equation obtained for the experiments in the several phases, were for Egg: 1/D
      = -0.18 + 0.02. T; Larva: 1/D = -0.028 + 0.01. T; Pupa: 1/D = -0.069 + 0.01. T;
      and Adult: 1/D = -0.4178 + 0.02. T. In function of temperature, S. nudiseta can
      present from 4.18 to 8.95 and from 4.91 to 8.99 generations per year, when
      calculated through the equations of development and through the simulations,
      respectively. And the higher the temperature the larger the generation number.
      Through variance analysis it was verified the significance for the regression
      equations in relation to the annual generation number (Ng/year) of S. nudiseta in
      function of the isothermals, for two studied situations. It was obtained a
      significance of 0,1%. The regression equations obtained for these situations
      were: Ng/year = 5.4 + 0.5. T and Ng/year = 5.1 + 0.52. T. The number of
      generations of S. nudiseta varies linearly with the isothermal. Besides that, the
      number of annual generations for each isothermal does not differ statistically
      when calculated through the development equations or through the simulations.
      Such conditions suggest the adaptation of the deterministic model adopted.

PMID- 11340473
TI  - Morphology and anatomy of developing fruits and seeds of Vismia guianensis
      (Aubl.) Choisy (Clusiaceae).
AB  - Morphological, structural and developmental features of fruits and seeds of
      Vismia guianensis (Aubl.) Choisy. are here presented, with the purpose to
      elucidate their structure and to contribute to taxonomical and ecological studies
      of the family. The fruit is a berry and the "rind" is constituted by the exocarp
      and by the subepidermal layers which constitute the mesocarp. The reddish pulp,
      rich in starch, is constituted by the parenchymatic mesocarp, with branched
      secretory ducts and vascular bundles, joined with the endocarp, which arises from
      a ventral meristem. The bitegmic, anatropous ovules, provided by the endothelium,
      develop into anatropous, bitegmic and exalbuminous seeds. The reddish uniseriate
      testa shows phenolic contents. The tegmen becomes crushed resting only the
      uniseriate exotegmen with undulate, thick walled and lignified cells, which
      contain a number of calcium oxalate prismatic crystals. The embryo, rich in
      lipids, is straight and shows foliaceous cotyledons.

PMID- 11340474
TI  - Triceratium moreirae sp. nov. and Triceratium dubium (Triceratiaceae -
      Bacillariophyta) from estuarine environments of Southern Brazil, with comments on
      the genus Triceratium C. G. Ehrenberg.
AB  - A new species of Triceratiaceae is described for estuarine environments of
      Southern Brazil. The valve of Triceratium moreirae sp. nov. is triangular with
      elevations bearing ocellus and a rimoportula in their basis. The valvar surface
      has robust pseudoloculi, circular to polygonal, each one confining a group of
      areolae arranged in a typical pattern. A central larger areola is surrounded by 5
      8 smaller areolae, and they are poroidal with domed cribra. A septum emerges from
      the valvocopula, having the base reinforced by ribs and the margins folded to the
      innerside of the valve. The new species is compared to the closely related diatom
      Triceratium dubium, which has the same pattern of areolar disposition, formation
      of septum and pseudoloculi. The main differences in relation to T. moreirae are:
      rimoportulae intercalated to ocelli and with a characteristic morphology
      (spinules on the edge of the external aperture), and more elongated elevations
      with a constriction. Some criteria used for the classification of categories into
      the Triceratiaceae are also discussed, and we propose that the type of areola
      (poroidal with cribra) be included in the circumscription of Triceratium.

PMID- 11340475
TI  - Toxicology of Lapachol in rats: embryolethality.
AB  - Lapachol is a naphtoquinone with therapeutic potential against enterovirus,
      Chagas disease and is also used as an antimalarial and antiinflamatory agent. In
      order to study teratogenic potential of Lapachol, pregnant Wistar rats were
      treated with 0.5 ml of distilled water (control group); 0.5 ml of hydroalcoholic
      solution (vehicle group) and 10 mg of Lapachol in 0.5 ml of hydroalcoholic
      solution (treated group) by oral gavage from the 8th to the 12th day of
      pregnancy. The following variables were observed: maternal body weight on days 1,
      6, l5 and 21 and food intake on days 2, 6, 15 and 21 of pregnancy. The number of
      live and dead fetuses and the sites of resorptions were counted. The ovaries were
      weighed and the corpora lutea were counted. Data were analyzed by ANOVA-one way,
      Dunnett test and the chi square test. Significance level test alpha = 0.05.
      Results have shown that mothers were unaffected but there were a 99.2% of fetus
      mortality, indicative of a strong abortifacient effect of Lapachol in rats.

PMID- 11340476
TI  - Endemic Pemphigus foliaceus ("Fogo selvagem"): a series from the Northeastern
      region of the State of Sao Paulo, Brazil, 1973-1998.
AB  - Endemic Pemphigus Foliaceus (EPF) is a bullous autoimmune skin disease whose
      incidence used to be high in the State of Sao Paulo (SP), Brazil, during the
      forties, but has declined thereafter. OBJECTIVES: to report a series of EPF
      patients from the northeastern region of SP. METHODS: a retrospective study
      concerning demographic and epidemiological data of patients seen from 1973 to
      1998 was conducted at the University Hospital, Faculty of Medicine of Ribeirao
      Preto, SP. RESULTS: bullous disease was diagnosed in 340 patients, 245 with EPF
      (72.1%), 9.4 cases per year, 60.4% females, and 70.2% white, 7 to 82 year-old
      (29.4% in their teens); 46.9% lived in the rural zone. Concerning profession,
      housewives predominated among women (67.6%) and agricultural workers among men
      (40.2%). The time of disease was less than 1 year in 62.0% of cases, followed by
      1 and 5 years (27%), and more than 5 years for the remaining patients (11%).
      36.7% of patients were referred by the Direcao Regional de Saude (DIR) XVIII of
      Ribeirao Preto, with the largest number of cases being from Ribeirao Preto and
      Batatais: 33.3% and 23.3%, respectively; 22% from DIR XIII (Franca); 13.5% from
      DIR VII (Araraquara); 2.9% from DIR IX (Barretos); 4.1% from other DIRs of SP,
      and 20.8% from other States (16.7% from Minas Gerais). Thirteen (5.3%) patients
      reported occurrence of the disease in some relative, and 4 (1.6%) in neighbors.
      CONCLUSIONS: the present data characterize the northeastern region of the state
      of Sao Paulo as a remaining endemic focus of EPF.

PMID- 11340477
TI  - Schistosoma mansoni: inflammatory foci around larvae in the peritoneal cavity of
      naive mice is radiosensitive.
AB  - Innate attack to Schistosoma mansoni cercariae was evaluated in irradiated mice.
      It was observed that 70% of the larvae from mice sacrificed one day after whole
      body irradiation with 400 or 800 rads were surrounded by cluster reactivities,
      without difference from controls. Differences were apparent on day 5 after
      irradiation with sub lethal (400 rads) or lethal doses (800 rads) suggesting that
      innate defence to infection take at least 5 days to be affected by low dose whole
      body radiation.

PMID- 11340478
TI  - Pyogenic abscesses and parasitic diseases.
AB  - Parasitic diseases which during their course in the host switch the immune system
      from a T helper 1 to a T helper 2 response may be detrimental to the host,
      contributing to granuloma formation, eosinophilia, hyper-IgE, and increased
      susceptibility to bacterial and fungal infections. Patients and animals with
      acute schistosomiasis and hyper-IgE in their serum develop pyogenic liver abscess
      in the presence of bacteremia caused by Staphylococcus aureus. The Salmonella-S.
      mansoni association has also been well documented. The association of tropical
      pyomyositis (pyogenic muscle abscess) and pyogenic liver abscess with Toxocara
      infection has recently been described in the same context. In tropical countries
      that may be an interesting explanation for the great morbidity of bacterial
      diseases. If the association of parasitic infections and pyogenic abscesses
      and/or fungal diseases are confirmed, there will be a strong case in favor of
      universal treatment for parasitic diseases to prevent or decrease the morbidity
      of superinfection with bacteria and fungi.

PMID- 11340479
TI  - Pancreatic involvement in co-infection visceral leishmaniasis and HIV:
      histological and ultrastructural aspects.
AB  - The involvement of the gastrointestinal tract in the co-infection of HIV and
      Leishmania is rarely reported. We report the case of an HIV-infected adult man co
      infected with a disseminated form of leishmaniasis involving the liver, lymph
      nodes, spleen and, as a feature reported for the first time in the English
      literature, the pancreas. Light microscopy showed amastigote forms of Leishmania
      in pancreatic macrophages and immunohistochemical staining revealed antigens for
      Leishmania and also for HIV p24. Microscopic and ultrastructural analysis
      revealed severe acinar atrophy, decreased zymogen granules in the acinar
      cytoplasm and also nuclear abnormalities such as pyknosis, hyperchromatism and
      thickened chromatin. These findings might correspond to the histologic pattern of
      protein-energy malnutrition in the pancreas as shown in our previous study in
      pancreas with AIDS and no Leishmania. In this particular case, the protein-energy
      malnutrition may be due to cirrhosis, or, Leishmania or HIV infection or all
      mixed. We believe that this case represents the morphologic substratum of the
      protein energy malnutrition in pancreas induced by the HIV infection. Further
      studies are needed to elucidate these issues.

PMID- 11340480
TI  - Contribution to the laboratory diagnosis of human cryptosporidiosis.
AB  - Human cryptosporidiosis is an infection caused by Cryptosporidium spp, a
      coccidial protozoan of emergencial pathogenicity and responsible for severe and
      prostrating watery diarrhea, mainly in immunocompromised patients. Smears of
      stools submitted to concentration and staining by carbol fuchsin technique has
      been used in our laboratory as a diagnostic procedure for cryptosporidiosis. The
      long time observing the smears in the microscope due to the small size of the
      forms and the low contrast of the staining led us to introduce some modifications
      in the original protocol for the acid-fast staining. The smears were treated with
      the carbol fuchsin solution for 3 minutes as recommended by LENNETTE et al., 1985
      and the solution of the ethyl alcohol 70%-chloride acid 0.5% was used instead of
      the ethyl alcohol-sulfuric acid 5% recommended by HENRIKSEN & POHLENZ, 1981.
      Smears were treated with the discoloration solution for 2 minutes. These
      modifications promoted a better washing out of the excess of carbol fuchsin
      therefore increasing the dye efficiency. In such conditions, the visualization of
      protozoan oocysts on the slides examined became easier. They were observed by the
      contrast of their intense pink-reddish pigmentation against the blue background.
      It's worthwhile to emphasize that these modifications offer advantages when time
      and accuracy are concerned.

PMID- 11340481
TI  - Dermatophytoses in children: study of 137 cases.
AB  - Dermatophytoses are common fungal infections caused by dermatophytes but there
      are few data about this condition in the childhood. 137 children below the age of
      12 and clinically diagnosed as tineas were investigated prospectively at
      Instituto de Puericultura e Pediatria, Rio de Janeiro, from 1994 to 1999. Hair,
      skin/nails scraping and pus swabs were collected from lesions and processed for
      fungus. Male children from 2 to 12 years were mostly affected; tinea capitis (78
      cases) mainly caused by Microsporum canis (46 cases) was the most common clinical
      form. Tinea corporis (43 cases) mainly caused by Trichophyton rubrum (17 cases)
      accounted for the second most frequent clinical form. Tinea cruris (10 cases)
      with Trichophyton rubrum (5 cases) as the most common etiologic agent accounted
      for the third most frequent clinical form. Tinea pedis and tinea unguium were
      much less frequent (3 cases each). Trichophyton rubrum was the most common
      etiologic agent isolated in these cases (3 cases).

PMID- 11340482
TI  - Tinea capitis: study of asymptomatic carriers and sick adolescents, adults and
      elderly who live with children with the disease.
AB  - Tinea capitis is a dermatophyte infection that occurs mainly in childhood; there
      are few reports, in Brazil, in adolescents and adults. The detection of
      asymptomatic carriers is of great importance in the disease control. From
      February 1998 to February 1999, a study was performed at the outpatient
      Dermatologic Unit of Instituto de Puericultura e Pediatria Martagao Gesteira
      (Universidade Federal do Rio de Janeiro, Brasil) to verify the frequency of
      asymptomatic carriers and tinea capitis between 79 adolescents, adults and
      elderly who lived in the same household of 56 children (0-12 years) with tinea
      capitis. Of these, one female and one male adults (2.5%) were asymptomatic
      carriers and the cultures revealed Trichophyton tonsurans and Microsporum canis
      respectively. One female adolescent and two female adults (3.8%) had tinea
      capitis and all cultures revealed Trichophyton tonsurans. The study has shown
      that adolescents and adults who live in the same household of children with tinea
      capitis may be sick or asymptomatic carriers.

PMID- 11340483
TI  - Dental caries experience in Indians of the Upper Xingu, Brazil.
AB  - The present study describes the experience of dental caries in Indians
      communities of the Xingu, in order to supply parameters for further analysis of
      trends of the disease in Indians. We performed oral health examination in 288
      Indians from four communities (Yawalapiti, Aweti, Mehinaku and Kamaiura) living
      in the southern part of the Xingu National Park, using international criteria
      defined by the World Health Organization. The outcome measures were the DMFT and
      dmft scores, and the care index. Indians of the Upper Xingu presented high levels
      of caries, in all age groups. The average DMFT for 11 to 13-year-old children -
      5.93 - was lower than the index measured in 1993 for 12-year-old schoolchildren
      in nearby cities - 8.23 -, whose United Nations' human development index ranked
      medium. However, Indians presented a much lower care index, per age group, than
      these cities, and a high ratio of missing teeth for persons above 20 years old.
      These observations indicate low incorporation of dental care services. The
      irregularity of the services programmed for these communities, and the changing
      dietary and cultural patterns, mainly derived from their contact with the non
      indigenous population of Brazil, reinforce the pressing need for health promotion
      initiatives aimed at these groups.

PMID- 11340484
TI  - Study of a cutaneous leishmaniasis outbreak in General Vedia, Province of Chaco,
      1996.
AB  - Between March and July 1996, a focalized epidemic outbreak of cutaneous
      leishmaniasis in General Vedia, province of Chaco, associated to the gallery
      forest of the Oro river was verified. The incidence rate in the area, which was 0
      2/000 cases in preceding years, reached 8/000 cases in 1996. The risk of
      symptomatic infection was similar between sexes, but was different when analyzing
      the different age groups by sex, suggesting a greater relative importance of the
      peridomestic transmission for the females and of the transmission in the
      subtropical forest for the males. Specimens of Lutzomyia intermedia, a species
      already incriminated as a vector of Leishmaniasis in other provinces of northern
      Argentina, were captured and identified in the focus locality in May 1996. The
      possible causes of the outbreak related to the climatic variables and the vector
      abundance are analyzed and the results in the framework of possible preventive
      and control activities are discussed.

PMID- 11340485
TI  - American cutaneous leishmaniasis outbreak, Tartagal city, province of Salta,
      Argentina, 1993.
AB  - An American cutaneous leishmaniasis outbreak, with cases clustering during 1993
      in Tartagal city, Salta, was reported. The outbreak involved 102 individuals,
      43.1% of them with multiple ulcers. Age (mean: 33 years old) and sex distribution
      of cases (74.5% males), as well as working activity (70 forest-related), support
      the hypothesis of classical forest transmission leishmaniasis, despite the fact
      that the place of permanent residence was in periurban Tartagal. Moreover, during
      July, sandflies were only collected from one of the 'deforestation areas'.
      Lutzomyia intermedia was the single species of the 491 phlebotomines captured,
      reinforcing the vector incrimination of this species. Most infections must have
      been acquired during the fall (April to June), a pattern consistent with previous
      sandfly population dynamics data. Based on the epidemiological and entomological
      results, it was advised not to do any vector-targeted periurban control measures
      during July. Further studies should be done to assess if the high rate of
      multiple lesions was due to parasite factors or to infective vector density
      factors.

PMID- 11340486
TI  - Occurrence of Cryptosporidium oocysts and Giardia cysts in raw water from the
      Atibaia River, Campinas, Brazil.
AB  - Cryptosporidium parvum and Giardia duodenalis are waterborne parasites that have
      caused several outbreaks of gastrointestinal disease associated with drinking
      water. Due to the lack of studies about the occurrence of these protozoa in water
      in the Southeast of Brazil, an investigation was conducted to verify the presence
      of cysts and oocysts in superficial raw water of the Atibaia River. The water
      samples were submitted to membrane filtration (3.0 microm) and elution was
      processed by (1) scraping and rinsing of membrane (RM method) and (2) acetone
      dissolution (ADM method). Microbiologic and chemical parameters were analyzed.
      Aliquots of the pellets were examined by immunofluorescence (Merifluor, Meridian
      Diagnostics, Cincinnati, Ohio). All water samples were positive for
      Cryptosporidium and Giardia, in spite of the high turbidity. Higher recovery
      rates occurred in samples treated by the RM method than by the ADM technique. The
      goal for future work is the assessment of viability of cysts and oocysts to
      determine the public health significance of this finding.

PMID- 11340487
TI  - Trypanosoma cruzi parasitemia observed in immunocompromised patients: the
      importance of the artificial xenodiagnosis.
AB  - Trypanosoma cruzi parasitemia observed in immunocompromised patients (transplant
      or positive HIV) occurred more frequently by the artificial xenodiagnosis method
      (10/38) compared with hemoculture (2/38), given the same quantity of blood. Other
      ways of diagnosis, like mice inoculation (5/38), QBC and buffy coat (2/38), were
      evaluated also. This result showed the importance of the artificial
      xenodiagnosis. The other techniques increased only one more patient positive.

PMID- 11340488
TI  - Validity of neck stiffness as a predictor for death from tetanus.

PMID- 11340490
TI  - Infectrons and coevolution.

PMID- 11340491
TI  - [Cutaneous leishmaniasis in the Metropolitan Region of Belo Horizonte: clinical,
      laboratorial, therapeutic and prognosis features (1989-1995)].
AB  - This study investigated clinical, laboratorial, therapeutic and prognostic
      aspects of American cutaneous leishmaniasis in Belo Horizonte in 358 patients
      with cutaneous leishmaniasis (CL) and 25 with mucocutaneous leishmaniasis (MCL).
      Compared to CL patients, the MCL patients reported longer duration of disease and
      higher frequency of other diseases, suggesting that debilitation caused by
      leishmaniasis or other conditions might contribute to activation and/or mucous
      dissemination of the parasite. The sensitivity of skin test, indirect
      immunofluorescence reactions and direct detection of parasites was 78.4, 79.3 and
      68.3%, respectively. The treatment with meglumine antimoniate presented 100%
      efficacy, but 59% patients had side-effects. During two years of follow-up, there
      were 32/318 relapses after successful treatment. Most relapses (31/32) were of CL
      patients treated with 15 mg Sb5+/kg/day. The negative response to skin test was
      the only factor associated with a significant threefold increased risk of
      relapse. Higher dose or longer duration of treatment might improve the prognosis
      in these patients.

PMID- 11340492
TI  - [Hantavirus pulmonary and cardiovascular syndrome: epidemiology, clinical
      presentation, laboratory diagnosis and treatment].
AB  - The Hantavirus pulmonary and cardiovascular syndrome (HPCVS) is an emerging
      disease in Brazil. In this study, eight confirmed cases of HPCVS were studied.
      All the patients presented fever and dyspnea as well as thrombocytopenia and
      hypoxemia. Tachycardia, malaise, hypotension and lung rales occurred in 75 to
      87.5% of the cases. Hemoconcentration, blood cell count increased and immature
      neutrophils, and high levels of creatinine were observed in 75 to 87.5%.
      Intravenous liquid infusion, the use of drugs for increasing systemic vascular
      resistance and inotropism, and mechanic ventilation were used for the patients.
      Mechanical ventilation and volume administration should be started precociously,
      preferable in intensive care units employing recommended universal and
      respiratory precautions. Careful volume administration should be limited if signs
      of pulmonary edema develop. Mortality (50%) is high and probably related to the
      severity of the disease as well as to a delayed attending of the patients for
      intensive management. It is important to report hantaviruses and HPCVS to the
      Brazilian medical community considering that many cases could be undiagnosed.

PMID- 11340493
TI  - [Growth retardation in children with positive intradermic reaction for
      leishmaniasis: preliminary results].
AB  - The objective of this study was to compare growth retardation frequency, and 24-h
      food intake data of children with or without positive Montenegro (leishmanin)
      test, examined in Porteirinha town, Brazil. Daily nutrient intake was determined
      by 24-h food intake recall and the anthropometric data were compared to the
      standard values from WHO. Montenegro-positive (n = 9) and Montenegro-negative (n
      = 17) groups showed similar age (5.5 +/- 1.9 vs 6.7 +/- 2.3y), and energy
      (1,456.8 +/- 314.8 vs 1,316.2 +/- 223.8kcal) and protein (50.4 +/- 16.7 vs 49.9
      +/- 13.9g) daily consumption, respectively. Montenegro-positive children had
      higher percentage of stunting than their Montenegro-negative counterparts (44.4
      vs 5.9), suggesting that previous Leishmania sp infection had negative impact on
      children's nutritional status.

PMID- 11340494
TI  - A longitudinal study on enteropathogenic infections of livestock in Trinidad.
AB  - A longitudinal study was conducted on selected livestock farms to determine the
      prevalence of enteropathogens in diarrhoeic and non-diarrhoeic animals. The
      enteropathogens assayed from faecal samples and rectal swabs were bacteria
      (Escherichia coli, Campylobacter spp. Salmonella spp. and Yersinia
      enterocolitica), parasites (coccidia, gastrointestinal nematodes and
      Cryptosporidium spp.) and viruses (group A rotavirus and parvovirus). The
      prevalence of the enteropathogens in various animal species was related to age
      and month of the year. Generally, younger animals presented a higher prevalence
      of infection by enteropathogens than older animals while most infections occurred
      between the months of January and April.

PMID- 11340495
TI  - [Monitoring of vegetables sold in Ribeirao Preto, SP, Brazil].
AB  - The ingestion of raw vegetables represents an important means of transmission of
      several infectious diseases. The objective of the present study was to perform a
      microbiological and parasitological evaluation of the vegetables commercially
      sold in the municipality of Ribeirao Preto, SP, Brazil. Of a total of 172
      commercial concerns analyzed, 115 (67%) presented irregularities in the
      vegetables they sold, such as elevated concentration of fecal coliforms in 63%,
      presence of Salmonella in 9%, and presence of enteroparasites in 33%. The
      commercial concerns with the highest frequencies of vegetables showing inadequate
      results were: grocery stores (92%), CEAGESP (75%), fruit and vegetables stores
      (71%), traveling vendors (71%), fairs (69%), supermarkets (52%), and vegetable
      gardens (18%). The type of contamination was uniformly distributed among these
      commercial concerns. Most of the contaminated vegetables (61%) were from gardens
      located in the municipality of Ribeirao Preto. Considering the high frequency of
      fecal contamination and the potential risk of disease transmitted by vegetables,
      we suggest greater enforcement in the sanitary surveillance of the food offered
      to the population.

PMID- 11340496
TI  - [Malaria in the state of Parana, Brazil].
AB  - To collect data regarding registered cases of malaria in the state of Parana,
      attendance reports of suspected cases of malaria performed by Fundacao Nacional
      de Saude, Parana regional center, were analyzed from January, 1994 through
      December, 1999. Of 31,975 blood samples examined, 7.4% were positive: 86.4% for
      Plasmodium vivax, 12.7% for P. falciparum, 0.04% for P. malariae and 0.9% for P.
      vivax and P. falciparum. As to the epidemiological classification, 84.5%
      represented heterochthonous cases and 15.5% represented autochthonous cases. The
      municipalities showing higher rates of autochthonous cases were Foz do Iguacu,
      Santa Terezinha do Itaipu and Santa Helena, a region influenced by the Itaipu
      reservoir, where prevention and control actions must be concentrated.

PMID- 11340497
TI  - [Effect of freezing on immunogenicity of the rabies vaccine produced in suckling
      mouse brain].
AB  - The immune humoral response induced by the rabies vaccine produced in suckling
      mouse brain was studied in 23 dogs. The mouse neutralization test (MNT) was used
      to evaluate the level of rabies antibodies. Ten dogs received vaccine stored at 2
      to 8 degrees C, showing the following results: 30 days after vaccination, six
      samples (60%) responded to the MNT; 180 days after vaccination, 4 samples (40%);
      and 360 days after vaccination, only one sample (10%). The remaining 13 dogs
      received previously frozen vaccine and 30 days after vaccination, only two
      samples (l5.4%) responded to the MNT. No titers were detected 180 and 360 days
      after vaccination. Statistical analysis of each variable used Tuckey analysis of
      variance, which showed statistically significant differences between the two
      groups.

PMID- 11340499
TI  - [One century of experience with the control of ancylostomiasis].
AB  - In the beginning of the XX century, ancylostomiasis was considered a serious
      public health problem and governments started the first systematic planning for
      the control of an endemic disease, in large scale. Thereafter, ancylostomiasis
      was considered a less important subject, because efficient anti-helminthic drugs
      were introduced, this in combination with the economic development in rich
      countries, reduced undernourishment and improved housing and sanitary conditions.
      Consequently, the residual cases of the infection became in general asymptomatic.
      However, in the third world the problem is still present, and must be considered
      with realism and managed accordingly. Various suggestions for controling the
      disease are presented in this paper.

PMID- 11340498
TI  - [Serological markers of hepatitis B in users of services at an HIV Testing
      Center].
AB  - The objective of this investigation was to study the prevalence of serological
      markers of hepatitis B and possible risk factors for this disease in a sample of
      404 people who attended a Testing and Couseling Center for HIV in the city of
      Ribeirao Preto, Sao Paulo State, Brazil. The overall prevalence of serologic
      hepatitis B markers was 14.6%, equal to that obtained for anti-HBc. HBsAg and
      anti-HBc IgM showed prevalences of 1%. After adjustment using logistic
      regression, hepatitis B markers showed association with the following variables:
      age, place of residence, use of injectable drugs and positivity to anti-HIV. The
      overall prevalence of human immunodeficiency virus infection was 6.9%. Hepatitis
      B markers were detected in 55.6% among intravenous drug users and in 42.9% among
      those who tested positive for HIV, confirming literature findings which indicates
      high levels of infection in these specific population groups.

PMID- 11340500
TI  - [Hepatitis C].
AB  - It has been estimated that 3% of the world population is infected with the
      hepatitis C virus. Those who are blood product recipients or have been illicit
      drug users are at risk. Dental and medical procedures as well as tattooing and
      acupuncture are also risk factors. Chronic infection occurs in up to 85% of
      infected cases but they may remain without symptoms during years or even decades,
      and clinical presentation varies. Determination of anti-HCV in sera is a fairly
      sensitive tool for the diagnosis, and confirmation requires the identification of
      HCV-RNA. Staging of the liver disease as well as definition of its present
      activity can be graded by liver biopsy. The aim of treatment is to stop the
      progression of the hepatic disease by inhibiting viral replication. Due to the
      low therapeutic efficacy combined with important side-effects, the administration
      of interferon and ribavirin have specific indications and contraindications.
      Predictive factors of therapeutic response, particularly viral load and genotypes
      of HCV, are useful in the evaluation of patients.

PMID- 11340501
TI  - [Pulmonary adiaspiromycosis: casual finding in a patient who died of yellow
      fever].
AB  - During an outbreak of yellow fever (rural form of the infection) occurred
      recently in the State of Goias, Brazil, a patient, with clinical manifestations
      suggestive of the infection, died in the University Hospital of Brasilia, DF, on
      the fifth day from admission. Postmortem examination revealed, microscopically,
      the characteristic alterations of the infection, and discovered in the lungs and
      hilar lymph nodes round microrganisms identified as adiaconidia of Emmonsia parva
      var. crescens.

PMID- 11340502
TI  - [Outbreak of bubonic plague in Jacocha, Huancabamba, Peru ].
AB  - Climatic alterations arising in the north of Peru as a result of the El Nino
      phenomenon (ENSO) have caused variations in the crop volume, changes in the
      direction of rivers and probably an increase in the rodent population. In
      February 1999, in a native community in Jacocha, Huancabamba, Piura's mountains,
      Peru, an outbreak of bubonic plague appeared with five human cases, one of which
      lead to death. The diagnosis was confirmed by serology (passive hemaglutination).
      The presence of antibodies in dogs of localities close to Jacocha has confirmed
      the circulation of Yersinia pestis in the region. The outbreak was controlled by
      the local sanitary authorities' prompt action. This episode, after an
      epidemiological silence for more than four years, showed the necessity of
      intensifying the plague epidemiological surveillance system in this area.

PMID- 11340503
TI  - [Comparison of 4 techniques for the diagnosis of Giardia lamblia in stool of
      children from Belem city, Para State, Brazil].
AB  - We report the evaluation of four techniques for Giardia lamblia diagnosis in
      children's stool. The Iron haematoxilin staining and direct examination with
      lugol showed lower positivity, while the method of Faust et al. Continues to be a
      good option for G. lamblia diagnosis and Immunoenzymatic assay increases the
      detection of this parasite.

PMID- 11340504
TI  - Report on the occurrence of Angiostrongylus costaricensis in southern Brazil, in
      a new intermediate host from the genus Sarasinula (Veronicellidae, Gastropoda).
AB  - Veronicellid slugs are the main intermediate hosts for Angiostrongylus
      costaricencis. In a rural locality in Nova Itaberaba (SC, southern Brazil)
      Sarasinula linguaeformis was identified as a crop pest. The parasitological
      examination revealed A. costaricencis infection in 43 out ot 50 slugs. The
      prevalence of 86% and the individual parasitic burdens are the highest sofar
      reported in Brazil and S. linguaeformis is the first species from the genus
      Sarasinula to be identified as intermediate host for A. costaricencis in southern
      Brazil.

PMID- 11340505
TI  - [Prevalence and intensity of infection by intestinal parasites in school-aged
      children in the City of Salvador (Bahia, Brazil)].
AB  - As part of a major study to evaluate the relationship between environmental
      changes and occurrence of the infection, prevalence and intensity of infection by
      intestinal parasites was studied in a sample of school children aged 7 to 14
      years living in the City of Salvador. The prevalence of infection by at least one
      species of protozoa or helminth was 66.1%. Prevalence of infection by helminths
      increased with age. For all helminth species male children presented the highest
      prevalence.

PMID- 11340506
TI  - [Meglumine antimoniate].

PMID- 11340507
TI  - [Biodegradable microspheres for intraocular drug administration].

PMID- 11340508
TI  - Dry eye: an unexpected inflammatory disease.

PMID- 11340509
TI  - [The ocular surface: a fascinating structure].

PMID- 11340510
TI  - [Technique of inverse scleral flap in the treatment of peripheral corneal defects
      (Abreu and Delgado technique)].
AB  - PURPOSE: To present a new easy-to-perform technique for the treatment of
      peripheral corneal defects (perforation or significant thinning), which has had
      good results. METHODS: This technique, which consists in sliding and suturing a
      limbal based inverted scleral flap (similar to the scleral flap used in glaucoma
      surgery) over the affected peripheral cornea, is described. We present 7 cases:
      one dellen, two marginal ulcers, two perforating traumatisms, one descematocele
      and one case of corneal thinning after pterygium surgery. RESULTS: All 7 cases
      were satisfactorily resolved without modifying either the astigmatism or visual
      acuity. CONCLUSIONS: This is an easy-to-perform technique which offers good
      results and although it has some limitations, it can be recommended for the
      treatment of many peripheral corneal defects (perforations and significant
      thinning).

PMID- 11340511
TI  - [Ocular complications after treatment with intravenous cidofovir for
      cytomegalovirus retinitis].
AB  - PURPOSE: To describe the ocular changes observed in six patients treated with
      intravenous cidofovir for cytomegalovirus retinitis. METHODS: We have studied six
      patients (12 eyes) treated with intravenous cidofovir. A complete ophthalmologic
      examination was performed before and after each dose during the follow-up period,
      paying special attention to intraocular pressure changes. RESULTS: Three cases of
      non-granulomatous anterior uveitis with good response to conventional treatment
      were detected. The intraocular pressure decreased after the administration of the
      two first doses of the drug (p<0.01), and was followed by stabilization of the
      intraocular pressure with the next doses. In two of the eyes (16.7%), the
      decrease in the intraocular pressure was more than 50% in comparison to the
      measurements at the onset of treatment. In three eyes (18.7%), we detected acute
      anterior uveitis, which responded well to conventional treatment. CONCLUSIONS:
      The intravenous administration of cidofovir for the treatment of cytomegalovirus
      retinitis is associated with important ocular changes that must be carefully
      observed in the follow-up of these patients.

PMID- 11340512
TI  - [Indocyanine green angiography and subretinal neovascularization. Patterns in age
      related macular degeneration].
AB  - PURPOSE: To determine the different angiographic patterns of neovascular
      membranes with indocyanine green in age-related macular degeneration (ARMD) and
      to establish the phase in which neovascularizations can be visualized most
      frequently. MATERIAL AND METHOD: We studied 56 eyes from 55 patients with a
      diagnosis of ARMD between April 98 and April 99. All patients underwent
      indocyanine green (ICG) and fluorescein digital videoangiography. We evaluated
      the pattern and the moment of identification of the neovascular membrane with
      both procedures. RESULTS: We found that 13 out of 56 eyes (23.2%) presented well
      defined subretinal neovascularization in fluorescein videoangiography while 43
      (76.8%) showed an occult pattern. ICG videoangiography was able to identify
      choroidal neovascularization in 89.3% of cases. The following patterns were
      found: Type I: visible neovascularization (17.9%), Type II: well-defined
      membranes with hypofluorescent margin (33.9%), Type III: high fluorescent focal
      membranes (hot-spots) (8.9%), Type IV: hyperfluorescent plaques that appeared
      only in late phases (10.7%), Type V: mixed types (17.9%). A high percentage of
      choroidal neovascularization was observed in early or medium phases of the
      angiogram (85.4%). CONCLUSIONS: Choroidal neovascularization in ARMD can appear
      with different patterns in the ICG videoangiographic study. The most frequently
      found pattern was that of well-defined membranes with a hypofluorescent margin. A
      high percentage of cases can be already visualized in the early phases of the
      angiogram.

PMID- 11340513
TI  - [Efficacy of topical povidone-iodine applied the day before cataract surgery to
      reduce conjunctival flora].
AB  - OBJECTIVE: To evaluate the efficacy of the topical use of periocular and
      conjunctival povidone-iodine solution applied the day before cataract surgery to
      reduce conjunctival flora. PATIENTS AND METHODS: Randomized and prospective
      clinical trial with 82 patients. The treatment group (41 patients) received an
      application of topical 10% povidone-iodine solution on the periocular skin and
      instillation of topical 5% povidone-iodine solution on the forniceal conjunctiva
      the day before and one hour before surgery. The control group (41 patients) only
      received the usual perioperative disinfectant. Conjunctival smears were obtained
      from in all patients at the end of the surgery and these were sent to the
      Microbiology Laboratory for culture. RESULTS: In the treatment group 1 positive
      culture was found in the 41 eyes (2.4%). In the control group, there were
      positive cultures in 6 out of 41 eyes (14.6%). The difference is statistically
      significant (p<0.05). CONCLUSIONS: The disinfecting of the periocular skin with
      10% povidone-iodine solution and of the conjunctiva with 5% povidone-iodine
      solution the day before and one hour before cataract surgery is effective in
      reducing conjunctival bacterial colonization compared with perioperative
      disinfection alone.

PMID- 11340514
TI  - [Treatment of the massive suprachoroidal hemorrhages].
AB  - PURPOSE: To analyze the anatomical and functional results obtained in post-
      surgical suprachoroidal hemorrhages treated from 1998 to 2000 and to review the
      information on the series of this complication that have been published during
      the last five years and which included at least 10 patients. METHODS: A
      retrospective analysis of the medical records of patients with suprachoroidal
      hemorrhages at the Instituto Universitario de Oftalmobiologia Aplicada (IOBA) -
      University Hospital of Valladolid. Bibliographic search by Med-Line/Pub Med from
      1995 to 2000 was performed. RESULTS: 8 patients who fulfill these criteria have
      been treated and 8 papers, also complying with the criteria, have been found.
      CONCLUSIONS: The functional and anatomic results of post-surgical suprachoroidal
      hemorrhages are still poor, even though the prognosis seems to have improved in
      the last 20 years. The standardized classification of massive suprachoroidal
      hemorrhages based on severity and the standardization of the follow-up would
      improve these results.

PMID- 11340515
TI  - [Treatment of retinal re-detachment in eyes with intraocular silicone oil].
AB  - PURPOSE: To describe the standardized surgical technique we used to treat
      recurrent retinal detachment in eyes that had been previously operated on with
      silicone oil. METHOD: We present 6 cases in which the following surgical steps
      were carried out as a standardized procedure: 1) silicone oil extraction, 2)
      partial introduction of perfluorcarbon liquids (PFCL), 3) extraction of
      epiretinal membranes, 4) endodiathermy, 5) retinotomy, 6) retinectomy, 7)
      complete filling of the intraocular cavity with PFCL, 8) endophotocoagulation and
      9) 5,000 Cs silicone oil injection. RESULTS: All the patients maintained the
      reattached retina. Five of them still have the silicone oil in the vitreous
      cavity. One patient suffered a macular epiretinal membrane. A second patient
      presented a macular epiretinal membrane with subfoveal PFCL as well as a relapse
      of the retinal re-detachment when we extracted the silicone oil during the
      macular surgery, so that it had to be re-introduced. All of the patients, except
      two who were aphakic, developed different degrees of cataracts. CONCLUSIONS: The
      systematic use of these surgical steps can be very useful in the management of
      retinal detachment relapses in eyes previously treated with silicone oil
      injection.

PMID- 11340517
TI  - [Progressive diffuse subretinal fibrosis syndrome: a case report].
AB  - CASE REPORT: The case of a 63 year old woman presenting fibrous subretinal
      lesions in the posterior pole on a routine ocular fundus check up is reported.
      The angiographic study showed a choroidal origin window defect next to
      hypofluorescence areas. The patient did not complain of vision loss or scotomas
      at any time. DISCUSSION: This clinical picture could be classified as a
      progressive subretinal fibrosis syndrome with atypical features. However, a
      differential diagnosis with other choroidal inflammatory conditions should be
      carried out even though many authors may consider them as different developmental
      phases of the same entity.

PMID- 11340516
TI  - [Comparative study between different conjunctival tissue adhesives].
AB  - PURPOSE: To evaluate efficacy and clinical and histopathological tolerance of a
      new acrylic tissue adhesive (ADAL-2) compared to sutures (Vicryl) and other
      available tissue adhesives (Tisuacryl) for their use in conjunctival surgery.
      METHODS: This was an experimental study performed in New Zealand albino rabbits
      with conjunctival dissection and closure by ADAL-2. Groups treated with Vicryl
      and Tisuacryl were compared regarding efficacy, clinical, and histological
      tolerance at 7, 28 and 42 days. RESULTS: Efficacy was similar in the three
      methods of conjunctival repositioning evaluated. Tolerance to ADAL-2 was similar
      to that of Vicryl suture and tolerance to ADAL-2 was superior to that to
      Tisuacryl. Histopathological results with ADAL-2 and Tisuacryl are similar.
      CONCLUSIONS: ADAL-2 tissue adhesive is an efficient and very well tolerated
      alternative for conjunctival closure in ophthalmic surgery.

PMID- 11340518
TI  - [Supposed nylon allergy after cataract surgery].
AB  - CASE REPORT: We present the case of a patient operated on for extracapsular
      cataract extraction of both eyes. Three weeks after the first operation (right
      eye), the patient presented a local inflammatory reaction at the incision site
      which was characterized by the existence of whitish exudates of different sizes
      surrounding the nylon suture. At one week of the second operation, the patient
      presented the same alteration (left eye), although it was observed sooner and had
      a greater intensity. The allergy skin tests for nylon and other substances were
      negative, however the local inflammatory reaction disappeared when the nylon
      suture was removed. DISCUSSION: This type of reaction, which we have observed in
      several other patients, has been previously described by others authors, although
      no clearly established cause has been demonstrated. Both toxicity and allergy to
      nylon have been proposed as the underlying mechanisms. We consider that a type IV
      hypersensitivity reaction to nylon may be the underlying mechanism of these
      reactions although toxicity cannot be ruled out.

PMID- 11340519
TI  - [Ocular ossification].

PMID- 11340520
TI  - [Rudaki Samarkandi, Persian poet. Rudak (859?)-Samarkand (941?)].

PMID- 11340521
TI  - pap genotype and P fimbrial expression in Escherichia coli causing bacteremic and
      nonbacteremic febrile urinary tract infection.
AB  - Escherichia coli strains from patients with febrile urinary tract infections
      (n=73) were examined for pap genotype and P fimbrial expression in relation to
      bacteremia and patients' background variables. Most isolates were pap(+) by DNA
      hybridization (n=51), and 36 were papG(IA2)(+) and 18 prsG(J96)(+) by polymerase
      chain reaction. The pap and papG genotypes of the infecting strain were shown to
      vary with host compromise, sex, and age. Bacteremia in noncompromised patients
      was caused by papG(IA2)(+) strains, but compromised hosts carried a mixture of
      papG(IA2)(+), prsG(J96)(+), and pap(-) strains. Women of all ages were infected
      with papG(IA2)(+) strains. Infected men carried prsG(J96)(+) or pap(-) strains
      and were older, and most had compromising conditions. papG(IA2)(+) strains
      predominated among patients with medical illness, whereas prsG(J96)(+) strains
      predominated among patients with urinary tract abnormalities. These findings
      emphasize the strong influence of host factors on the selection of E. coli
      strains causing febrile urinary tract infections.

PMID- 11340522
TI  - Association between antifungal prophylaxis and rate of documented bacteremia in
      febrile neutropenic cancer patients.
AB  - Published data have suggested a correlation between antifungal prophylaxis and
      bacteremia in febrile neutropenia. This correlation was investigated among 3002
      febrile neutropenic patients enrolled in 4 trials during 1986-1994. Globally,
      1322 patients (44%) did not receive antifungal prophylaxis; 835 (28%) received
      poorly absorbable antifungal agents and 845 (28%) received absorbable antifungal
      agents. The rates of bacteremia for these groups were 20%, 26%, and 27%,
      respectively (P=.0001). In a multivariate model without including antifungal
      prophylaxis, factors associated with bacteremia were: age, duration of
      hospitalization, duration of neutropenia before enrollment, underlying disease,
      presence of an intravenous catheter, shock, antibacterial prophylaxis,
      temperature, and granulocyte count at onset of fever. When antifungal prophylaxis
      was included, the adjustment quality of the model improved slightly (P=.05), with
      an odds ratio of 1.19 (95% confidence interval [CI], 0.92-1.55) for patients
      receiving nonabsorbable and 1.42 (95% CI, 1.07-1.88) for those who were receiving
      absorbable antifungal agents. Antifungal prophylaxis with absorbable agents might
      have an impact on the rate of documented bacteremia in febrile neutropenia. This
      effect should be confirmed prospectively.

PMID- 11340523
TI  - Antifungal antibiotics and breakthrough bacteremias.
AB  - Patients with fever and neutropenia are at high risk for infection (
      approximately 50%) and bacteremia ( approximately 20%). As a result, most are
      treated with antibacterial prophylaxis until their absolute neutrophil count
      exceeds 500 cells/mm(3) and their temperature returns to normal. The 1997
      guidelines of the Infectious Diseases Society of America suggested 1 of 3
      regimens: vancomycin plus ceftazidime, monotherapy with ceftazidime or imipenem
      (possibly cefepime or meropenem), or dual therapy with an aminoglycoside plus an
      antipseudomonal beta-lactam.

PMID- 11340524
TI  - Clinical and epidemiological features of Enterococcus casseliflavus/flavescens
      and Enterococcus gallinarum bacteremia: a report of 20 cases.
AB  - The clinical significance of intrinsically vancomycin-resistant enterococci is
      not yet fully established, as these organisms are infrequently recovered from
      clinical specimens. We report our experience with 20 cases of Enterococcus
      gallinarum and Enterococcus casseliflavus/flavescens bacteremia in humans from
      1992 through 1998. Sixteen cases of bacteremia were caused by E. gallinarum.
      Underlying conditions were present in 19 (95%) of the patients and included
      malignancy, receipt of transplant, and Caroli's disease. Polymicrobial bacteremia
      was present in 9 patients (45%). E. gallinarum and E. casseliflavus/flavescens,
      although they are infrequently isolated from clinical specimens, may cause
      serious invasive infections.

PMID- 11340525
TI  - Azithromycin-containing regimens for treatment of Mycobacterium avium complex
      lung disease.
AB  - Ninety-two patients were assessable in 3 consecutive, open, noncomparative,
      prospective, controlled, single-center trials of the use of multidrug regimens
      that contain azithromycin for treating pulmonary Mycobacterium avium complex
      (MAC) disease. Azithromycin was provided at a dose of 300-600 mg per day with
      oral companion drugs administered daily (regimen A, 29 patients); 600 mg 3 times
      weekly (t.i.w.), with oral companion drugs administered daily (regimen B, 20
      patients); and 600 mg (t.i.w.), with oral companion drugs administered t.i.w.
      (regimen C, 43 patients). All regimens included rifabutin (or rifampin) and
      ethambutol as companion drugs as well as initial streptomycin. Treatment success
      was defined as 12 months of negative cultures while on therapy. Treatment failure
      was defined as sputum culture positivity after at least 6 months of therapy. Of
      the patients in each regimen who reached study end points, 17 of 29 (59%) were in
      regimen A, 11 of 20 (55%) were in regimen B, and 28 of 43 (65%) were in regimen C
      met the treatment success criterion. There were no statistically significant
      differences in outcome between the 3 regimens. These studies demonstrate the
      effectiveness of daily and t.i.w. regimens containing azithromycin for treatment
      of MAC lung disease.

PMID- 11340526
TI  - Oropharyngeal candidiasis in patients with human immunodeficiency virus:
      correlation of clinical outcome with in vitro resistance, serum azole levels, and
      immunosuppression.
AB  - Azole-resistant thrush has emerged as a problem in people who are infected with
      human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS),
      especially those who have low CD4 cell counts who have had a previous relapse of
      oral candidiasis, and in those who require long-term suppressive antifungal
      therapy. Because of the development of a standardized methodology for antifungal
      susceptibility testing and interpretive criteria for resistance testing, studies
      of the clinical predictive value of in vitro results are possible. In this study,
      61% of organisms isolated from patients who were receiving azole therapy and who
      had clinically resistant thrush had minimal inhibitory concentration values that
      would classify the isolate as "resistant" or "susceptible dose dependent." In
      contrast, 86% of isolates from patients with thrush that was clinically
      responsive to an azole were classified in vitro as "susceptible" or "susceptible
      dose dependent." No resistant isolates were detected in samples obtained from
      asymptomatic control patients who were not exposed to azole drugs. Serum levels
      of azole and CD4 cell counts were also important parameters with regard to
      prediction of response. We conclude that in vivo and in vitro correlations
      compare favorably to studies of susceptibility testing in bacteria.

PMID- 11340527
TI  - Persistently positive culture results in a patient with community-acquired
      pneumonia due to Legionella pneumophila.
AB  - We describe a patient with community-acquired pneumonia due to Legionella
      pneumophila serogroup 6. This patient was found to have bronchoalveolar carcinoma
      of the lung by means of cytologic testing in 1 of 2 bronchoalveolar lavage
      samples, but no lesions were visible on bronchoscopy. Despite intravenous
      administration of azithromycin to the patient, repeat culture and polymerase
      chain reaction showed persistence of Legionella; the isolates remained
      susceptible to azithromycin. The patient did not respond to 14 doses of daily
      intravenously administered azithromycin. The poor outcome may have been partially
      due to the suspected underlying lung malignancy, as shown by cytologic
      examination, and by a delay in seeking medical attention.

PMID- 11340528
TI  - Probiotic agents and infectious diseases: a modern perspective on a traditional
      therapy.
AB  - There is an increasing scientific and commercial interest in the use of
      beneficial microorganisms, or "probiotics," for the prevention and treatment of
      disease. The microorganisms most frequently used as probiotic agents are lactic
      acid bacteria such as Lactobacillus rhamnosus GG (LGG), which has been
      extensively studied in recent literature. Multiple mechanisms of action have been
      postulated, including lactose digestion, production of antimicrobial agents,
      competition for space or nutrients, and immunomodulation. We have reviewed recent
      studies of probiotics for the treatment and control of infectious diseases.
      Studies of pediatric diarrhea show substantial evidence of clinical benefits from
      probiotic therapy in patients with viral gastroenteritis, and data on LGG
      treatment for Clostridium difficile diarrhea appear promising. However, data to
      support use of probiotics for prevention of traveler's diarrhea are more limited.
      New research suggests potential applications in vaccine development and
      prevention of sexually transmitted diseases. Further studies are needed to take
      full advantage of this traditional medical approach and to apply it to the
      infectious diseases of the new millennium.

PMID- 11340529
TI  - Probiotics demonstrating efficacy in clinical settings.

PMID- 11340530
TI  - User's guide to tuberculosis resources on the internet.
AB  - The World Wide Web has become a source of information for clinicians and
      researchers about virtually every aspect of tuberculosis (TB). We provide
      information about TB-related Internet portal sites. We classify selected TB
      related Web pages according to user needs. The questions that we address are as
      follows: (1) Where can I find scientific information about TB? (2) Where can I
      find epidemiologic data? (3) Where can I find literature for laypeople? (4) Where
      can I find recommendations, guidelines, and clinical decision-making algorithms
      for management of TB? (5) Where can I find research databases? (6) Where can I
      find research groups? (7) Where can I find resources for research, teaching, and
      training? (8) Where can I find information about regulatory action? The total
      number of TB-related Web pages is immense, their scope is vast, and their content
      is perpetually changing. Nonetheless, the sites identified here provide the
      reader with a manageable number of entry points to this increasingly important
      resource.

PMID- 11340531
TI  - Infectious disease pathology.
AB  - The anatomic pathologist performs an important role in the diagnosis or exclusion
      of infectious diseases. The morphologic interpretation of biopsies and cytologic
      preparations allows for the definitive establishment or exclusion of a wide
      variety of diseases. Once the pathologist has determined that a disease is likely
      to be due to an infection and has characterized the inflammatory response,
      associated microorganisms or viral-associated cytopathic effects should be
      recorded. Although some microorganisms or their cytopathic effects may be clearly
      visible on routine hematoxylin and eosin-stained sections, additional
      histochemical stains are often needed for their complete characterization. Highly
      specific molecular techniques, such as immunohistochemistry, in situ
      hybridization, and nucleic acid amplification, may be needed in certain instances
      to establish the diagnosis of infection. Through appropriate morphologic
      diagnoses and interlaboratory communication and collaboration, the anatomic
      pathologist contributes greatly to the diagnosis and treatment of infectious
      diseases.

PMID- 11340532
TI  - Nosocomial candiduria: a review.
AB  - Fungal infections of the urinary tract, especially those caused by Candida
      species, are becoming increasingly common. Often the line between Candida
      colonization and infection is blurred. Diagnosis typically depends on the
      discovery of pyuria with high colony Candida counts in the urine. To date, there
      have been few studies to have addressed treatment regimens for patients with
      candiduria. Fluconazole has become a mainstay of therapy; however, questions
      regarding when to treat, whom to treat, and how long to treat are still largely
      unanswered. Asymptomatic nosocomial candiduria does not frequently require
      treatment intervention, because morbidity is low and ascending infection and
      candidemia are rare complications. Treatment decisions are driven by an
      understanding of the anatomic site of infection. For Candida cystitis, the first
      line treatment is fluconazole, given orally. Ascending pyelonephritis usually
      requires the administration of a systemic antifungal agent and often requires
      correction of the obstruction or surgical drainage. More research is needed to
      define diagnostic criteria and therapeutic pathways. This review will attempt to
      summarize the state of the art of diagnosis and management of candiduria.

PMID- 11340533
TI  - Resistance to trimethoprim-sulfamethoxazole.
AB  - Sulfonamides have a glorious history. In 1935, they were the first class of true
      antimicrobial agents with life-saving potency. Today, 66 years later, increased
      bacterial resistance to sulfonamides and to trimethoprim (TMP), a synthetic
      antimicrobial agent that is 30 years younger than sulfonamides, has limited their
      use to only a few indications. In the treatment and prophylaxis of patients with
      urinary tract infections, trimethoprim-sulfamethoxazole (TMP-SMZ) or TMP alone is
      still considered the first-line drug of choice, although increased bacterial
      resistance to these agents has been linked with treatment failure. TMP-SMZ has a
      possible role as a second- or third-line treatment for patients who have
      respiratory tract infections. In the developing world, where this inexpensive
      drug is widely used as first-line treatment, bacterial resistance has caused
      problems, especially with regard to the treatment of patients with severe
      respiratory tract infections. Use of TMP-SMZ as prophylaxis for Pneumocystis
      carinii infection has rapidly increased the multidrug resistance of bacterial
      pathogens found in human immunodeficiency virus-infected patients. Today,
      detailed and reliable knowledge on the resistance of bacterial pathogens to both
      TMP-SMZ and TMP is an essential requirement for the safe and effective use of
      these drugs in all clinical settings.

PMID- 11340534
TI  - Impact of prophylaxis for Mycobacterium avium complex on bacterial infections in
      patients with advanced human immunodeficiency virus disease.
AB  - The epidemiology and natural history of bacterial infections among ambulatory
      patients with advanced human immunodeficiency virus (HIV) disease has not been
      well described. In this prospective study, 394 subjects were enrolled and
      followed at 8-week intervals for a median of 21 months. During follow-up, 164
      (42%) of 394 patients developed at least 1 bacterial infection. The most common
      infections were sinusitis, bacterial pneumonia, skin and soft tissue infection,
      and bronchitis. Serious bacterial infections (defined as bacterial pneumonia,
      bacteremia, or deep visceral abscess) were reported by 56 subjects (14%). Female
      sex, age of <40 years, and Karnofsky score of < or =80 were independent risk
      factors for bacterial infections. Prophylaxis with clarithromycin, trimethoprim
      and sulfamethoxazole, or both had significant protective effect. The occurrence
      of any confirmed bacterial infection was associated with a significantly
      increased risk of mortality. This study documents that bacterial infections are
      common among patients with advanced HIV disease, especially among women.

PMID- 11340535
TI  - Ototoxicity associated with use of nucleoside analog reverse transcriptase
      inhibitors: a report of 3 possible cases and review of the literature.
AB  - Although a variety of adverse effects have been attributed to treatment with
      nucleoside analog reverse transcriptase inhibitors (NRTIs) for human
      immunodeficiency virus type 1 (HIV-1) infection, only 5 cases of ototoxicity have
      been reported in the literature. We describe 3 additional cases of possible NRTI
      associated ototoxicity in HIV-1-infected patients, all of whom were aged >45
      years, had a history of noise-induced hearing loss, and reported tinnitus and
      deterioration in hearing in the setting of antiretroviral therapy. Reductions in
      mitochondrial DNA content induced by NRTIs, as well as mitochondrial DNA
      mutations associated with aging and HIV-1 infection, all may contribute to
      auditory dysfunction in older patients with HIV-1 infection. Prospective studies
      are necessary to determine the incidence of tinnitus and hearing loss among HIV-1
      infected patients and their relationship to the use of NRTIs.

PMID- 11340536
TI  - Kawasaki-like syndromes associated with human immunodeficiency virus infection.
AB  - Kawasaki disease is an acute febrile vasculitic syndrome of early childhood. It
      is very rarely seen in adults. Among the adult patients with Kawasaki disease who
      have been described, a disproportionate number are infected with human
      immunodeficiency virus (HIV). This suggests that the immunocompromised state may
      predispose individuals to this syndrome. We report our experience with 2 HIV
      positive patients who presented with Kawasaki-like syndromes and review the
      published literature on HIV-positive patients with similar syndromes.

PMID- 11340537
TI  - Hypercholesterolemia in a health care worker receiving thyroxine after
      postexposure prophylaxis for human immunodeficiency virus infection.
AB  - We report a case of hypercholesterolemia that occurred 2 weeks after the start of
      highly active antiretroviral therapy following a needlestick exposure to human
      immunodeficiency virus (HIV) in an HIV-negative health care worker who was
      receiving thyroid replacement therapy. The elevated thyrotropic hormone level and
      hypercholesterolemia resolved after the antiretroviral therapy was stopped.

PMID- 11340538
TI  - An outbreak of influenza a caused by imported virus in the United States, July
      1999.
AB  - We report 32 cases of culture-proven influenza A (A/Sydney) caused by virus
      imported into mainland US military barracks from Puerto Rico in July 1999.
      Despite the fact that the shelf life of the influenza vaccine is 18 months and
      that the outbreak strain was a component of the previous year's vaccine, no
      vaccine was available from manufacturers, owing to US Food and Drug
      Administration regulations. Formal consideration should be given to extending the
      date of expiration and to maintaining a supply of the influenza vaccine year
      round.

PMID- 11340539
TI  - Intracellular persistence of Staphylococcus aureus small-colony variants within
      keratinocytes: a cause for antibiotic treatment failure in a patient with
      darier's disease.
AB  - Intracellular persistence assays were performed with small-colony variants (SCVs)
      derived from a patient with Darier's disease from whom different phenotypes and
      genotypes of Staphylococcus aureus were isolated over a 28-month period; the
      assays revealed that >100-fold more SCV cells persisted intracellularly relative
      to the normal phenotype. The presence of intracellular S. aureus SCVs may protect
      against host defenses and antibiotic therapy and thus may have contributed to
      this patient's very prolonged skin infection.

PMID- 11340540
TI  - Lack of transmission of mycobacterium abscessus among patients with cystic
      fibrosis attending a single clinic.
AB  - We retrospectively analyzed 1062 respiratory specimens from 214 patients with
      cystic fibrosis, of whom 5 patients had 36 cultures positive for M. abscessus.
      Results of molecular typing demonstrated that each of these 5 patients carried a
      single unique strain (genotype), which suggests that it may not be necessary to
      segregate patients with CF who are colonized or infected with M. abscessus from
      those who are not.

PMID- 11340541
TI  - Usefulness of blood culture for hospitalized patients who are receiving
      antibiotic therapy.
AB  - We conducted a retrospective study to determine the yield of blood samples drawn
      for culture during the initial 72 h of antibiotic therapy given to 139 patients
      who were admitted to the hospital for community-acquired infections or fever. The
      yield of these blood cultures was predictable and rarely (in only 1 patient
      [0.72%]) isolated new pathogens.

PMID- 11340542
TI  - Susceptibility to antimicrobial agents of Stenotrophomonas maltophilia isolated
      from patients with cancer and bacteremia.

PMID- 11340543
TI  - Hepatitis a vaccine in liver transplant recipients.

PMID- 11340544
TI  - A small, randomized, placebo-controlled trial of the use of antiviral therapy for
      patients with chronic fatigue syndrome.

PMID- 11340545
TI  - Fascioliasis in Antalya.

PMID- 11340546
TI  - Isolation of Leclercia adecarboxylata from an infant with acute lymphoblastic
      leukemia.

PMID- 11340547
TI  - Cryptococcosis in patients with cancer.
AB  - Records of 31 patients with cancer who did not have known human immunodeficiency
      virus infection and who developed culture-proven cryptococcosis during the period
      of 1989-1999 (incidence of 18 cases per 100,000 admissions) were retrospectively
      reviewed. Several presentations of cryptococcosis were seen, including pulmonary
      in 19 patients (13 of which were symptomatic), disseminated in 6, meningeal in 3,
      and other, less common manifestations in 3. Hematologic malignancy (in 20
      patients [65%]) was the most common underlying disease. Lymphopenia was present
      in 19 patients (61%). Previous steroid use was noted in 16 patients (51%). The
      diagnosis of cryptococcosis was rarely suspected; lung and brain malignancy were
      frequent initial impressions. Cryptococcosis was diagnosed postmortem in only 2
      cases (6%). In cases of both pulmonary and meningeal cryptococcosis, the yield of
      invasive diagnostic procedures was good. Antifungal treatment was heterogeneous,
      but only 18% of patients who received it had treatment failure. Fluconazole
      monotherapy was successful in 92% of patients. In conclusion, cryptococcosis is
      rare in patients with cancer and appears to have a relatively good diagnostic
      yield and therapeutic outcome.

PMID- 11340548
TI  - Public health response to 2 clinical cases of blastomycosis in colorado
      residents.
AB  - We summarize the public health response after the identification of 2 cases of
      pneumonia caused by Blastomyces dermatitidis infection in Colorado residents. The
      response to these cases emphasizes the need for physicians to add fungal
      infection to the list of differential diagnoses for patients who have refractory
      pneumonia, even those who live in areas of nonendemicity.

PMID- 11340549
TI  - Medullary gnathostomiasis in a white patient: use of immunodiagnosis and magnetic
      resonance imaging.
AB  - A 48-year-old French diplomat presented with a sensory-motor paraparesis of rapid
      onset, leading to paraplegia. Successive magnetic resonance image scans showed
      lesions of the thoracic spinal cord that were at different levels from one
      examination to the next. Specific anti-gnathostome antibodies were detected by
      means of enzyme-linked immunosorbent assay and Western blot test in both plasma
      and cerebrospinal fluid. Albendazole treatment prevented disease progression, but
      only partial regression of the neurologic symptoms was obtained.

PMID- 11340550
TI  - Disseminated infection and colonization by Scedosporium prolificans: a review of
      18 cases, 1990-1999.
AB  - Scedosporium prolificans infection was analyzed in 18 patients from whom the
      fungus was isolated during the period 1990-1999. Of these 18 patients, 12 had
      some predisposing factor and either unconfirmed infection or colonization, and 6
      patients had confirmed disseminated infection: 4 patients with leukemia died, 1
      patient with breast cancer who underwent autologous bone marrow transplantation
      survived, and 1 patient with advanced acquired immunodeficiency syndrome died,
      although the fungal infection did not seem to affect his clinical symptoms.

PMID- 11340551
TI  - Effects of pubic symphysiodesis in dysplastic puppies.
AB  - OBJECTIVE: To determine the long-term effects of juvenile pubic symphysiodesis
      (JPS) in dysplastic puppies. STUDY DESIGN: Prospective, randomized, clinical
      trial. ANIMALS: Seven dysplastic Chesapeake Bay retrievers and 2 beagle-crosses
      (BX1 and 2). METHODS: Five puppies had JPS performed with electrocauterization at
      12, 16, 20, 22, and 24 weeks of age, respectively. Two puppies served as
      controls. BX1 and BX2 were used to obtain biopsies of the symphysis. Hips were
      evaluated for: pelvic development (transverse computerized tomography for
      acetabular angle [AA] and dorsal acetabular rim angle [DARA]); laxity [hip
      extended and stress radiography [distraction index (DI)]); Ortolani maneuver with
      reduction angles; acetabular coverage (Norberg angles); and function (coxofemoral
      range of motion, hip pain, and gait analysis by force-plate technique at 44 and
      137 weeks of age). RESULTS: The pubis fused prematurely in every puppy that was
      operated on with the JPS technique. Greater acetabular responses were related to
      younger ages at surgery. The final mean AA in dogs that had JPS was 25 degrees
      greater than preoperative values; 40% increased over control. The DARA final mean
      was 10 degrees, 52% less than preoperative values and 46% less than control. The
      final mean DI in dogs having JPS was 0.28, 47% improved over preoperative values
      and 58% better than control. Mean pelvic dimensions in dogs that had JPS were 18%
      less than control. Gait analyses were normal for all dogs at 137 weeks. No
      urinary or bowel complications occurred. CONCLUSIONS: Significant ventrolateral
      acetabular rotation, increased hip coverage, diminished hip laxity, normal pain
      free gait, and insignificantly reduced pelvic size occurred after JPS. CLINICAL
      SIGNIFICANCE: Dysplastic hips in young dogs were significantly improved by JPS.

PMID- 11340552
TI  - Effect of venous strangulation obstruction on length of equine jejunum and
      relevance to small-intestinal resection.
AB  - OBJECTIVE: To determine if venous strangulation obstruction (VSO) of the distal
      half of the equine small intestine would increase length of that segment. STUDY
      DESIGN: Halothane-anesthetized horses were assigned randomly to 3 groups of 5
      horses: Group 1 (controls)--the entire small intestine was measured and rubber
      shod clamps were applied to mark each end of the most distal 50% of the small
      intestine; Group 2--same procedure, except that VSO was induced in the distal 50%
      of the small intestine for 180 minutes; and Group 3--same initial procedure,
      except that VSO was induced for 90 minutes and followed by reperfusion for 90
      minutes. ANIMALS OR SAMPLE POPULATION: Fifteen horses. METHODS: The proximal and
      distal halves of the small intestine were measured before and at 180 minutes
      after clamps and ligatures were applied. At the end of the study, biopsies were
      taken to assess mucosal epithelial damage by light microscopy, and horses were
      euthanatized while under general anesthesia. RESULTS: Intestine subjected to VSO
      and VSO and reperfusion had marked hemorrhagic changes and thickening in the
      intestinal wall. Both groups had incurred a grade 2.8 of 5 mucosal injury by 180
      minutes. Total length of small intestine and length of the distal 50% did not
      change in the control group, but intestine subjected to VSO only and VSO and
      reperfusion had increased in length by 29% (P <.05) and 36% (P <.05),
      respectively. CONCLUSIONS: Small intestine of horses subjected to VSO can
      increase in length, and this change could cause an overestimate of the amount of
      intestine involved in an extensive strangulating lesion. CLINICAL RELEVANCE: An
      overestimate of the amount of intestine involved in an extensive strangulating
      lesion could lead to an overly pessimistic assessment of a horse's risk for
      postresection malabsorption and maldigestion. Therefore, estimates of the
      proportion of small intestine that is strangulated should be corrected for this
      potential error and the risk of malabsorption determined accordingly.

PMID- 11340553
TI  - One percent sodium carboxymethylcellulose prevents experimentally induced
      abdominal adhesions in horses.
AB  - OBJECTIVE: To evaluate the efficacy of 1% sodium carboxymethylcellulose (SCMC)
      for prevention of experimentally induced abdominal adhesions in horses. STUDY
      DESIGN: Prospective, controlled, experimental study. ANIMAL POPULATION: Twelve
      healthy adult horses. METHODS: The effect of 1% SCMC on adhesion formation was
      evaluated in 12 healthy horses by using an established model of serosal trauma to
      induce intraabdominal adhesions. After ventral median celiotomy, 2 separate areas
      of the jejunum were abraded, and three 2-0 chromic gut sutures were placed in
      each abraded area. Jejunal resection and end-to-end anastomosis was performed at
      2 sites distant to the abrasion sites. In treated horses (n = 6), 2 L of 1% SCMC
      was applied to the intestine before and after intestinal manipulation. In control
      horses (n = 6), 2 L of saline solution were applied to the intestine before and
      after surgical manipulation. All horses were euthanatized 10 days after surgery,
      and the abdominal cavity was evaluated for adhesion formation. The frequency of
      intraabdominal adhesions between groups was compared with a chi-square test.
      Statistical significance was set at P <.05. RESULTS: All control horses had
      intraabdominal adhesions. Fibrous adhesions were associated with both jejunal
      abrasion sites in 5 control horses. Fibrous adhesions were also associated with 1
      or both jejunal anastomotic sites in 5 control horses. Only 1 treated horse
      developed adhesions at the jejunal abrasion sites, and no adhesions were present
      at the anastomotic sites in the treated horses. There were significantly fewer
      adhesions in the SCMC treatment group compared with the control group (P <.05).
      CONCLUSION: In this experimental model, application of 1% SCMC reduced the
      frequency of intraabdominal adhesions at areas of serosal abrasion and at jejunal
      anastomotic sites. CLINICAL RELEVANCE: In horses at an increased risk for
      developing intraabdominal adhesions after intestinal surgery, the use of 1% SCMC
      during celiotomy may decrease the frequency of adhesion formation.

PMID- 11340554
TI  - Arthroscopic mosaic arthroplasty in the equine third carpal bone.
AB  - OBJECTIVE: To investigate survival and function of autogenous heterotopic
      osteochondral grafts in a site where injuries are common. STUDY DESIGN: Three
      osteochondral grafts were harvested arthroscopically from the femoropatellar
      joint and transplanted to the third carpal bone (C(3)). Nine months later,
      histologic, histomorphometric, and biochemical comparisons were made between the
      transplanted grafts in C(3) and tissue adjacent to the recipient site, the
      opposing radial carpal bone (C(r)), the donor site in the femoropatellar joint,
      and the sham-operated contralateral C(3). ANIMALS: One mixed-breed pony and 5
      Standardbred horses aged 3 to 8 years old. METHODS: Using instruments modified
      for equine use, four 4.5-mm-diameter osteochondral grafts were harvested
      arthroscopically from the distal aspect of the lateral trochlea of the right
      femur and inserted into the radial facet of the right third carpal bone. The
      fourth graft was kept as a donor-site control sample. Three months later, regular
      exercise was started and at 6 months, repeat arthroscopy was conducted to
      evaluate healing. The horses were euthanatized 9 months after transplantation,
      and comparisons were made between the grafts, opposing radial carpal bone, and
      contralateral third carpal bone. The assessment criteria included paravital
      staining, a modified Mankin scoring system, and biochemical analyses for collagen
      type, total collagen content, and sulfated glycosaminoglycan concentration.
      RESULTS: All horses were sound 21 days' postoperatively. At 6 months, all 18
      grafts were intact but somewhat soft and opaque compared with surrounding carpal
      cartilage. Nine months' postoperatively, the bony portions of the grafts were
      well integrated with the recipient sites, but 6 grafts had histologic evidence of
      cartilage degeneration. From biochemical analysis of grafts, there was little or
      no new repair tissue invading the experimental sites, but sulfated
      glycosaminoglycan (proteoglycan) loss from the transplanted cartilage was marked.
      CONCLUSIONS: Heterotopic transfer of osteochondral grafts from the distal aspect
      of the lateral femoral trochlea to the third carpal bone is feasible with minor
      modifications of human mosaic arthroplasty instruments. The bony portion of the
      osteochondral grafts was quickly remodeled to provide subchondral support to the
      transplanted articular cartilage. The loss of proteoglycan from the transplanted
      cartilage indicates that the grafts might have been injured during harvesting or
      insertion, or, more likely, did not remodel to meet the demands of a new
      biomechanical environment. CLINICAL RELEVANCE: These findings suggest that
      arthroscopic resurfacing of focal osteoarticular defects will not be successful
      in the long term unless donor and recipient sites can be matched with respect to
      cartilage thickness, biochemical constituents, and physical properties. Mosaic
      arthroplasty may be indicated in selected cases in which no other options exist
      to create a confluent cartilage-covered surface.

PMID- 11340555
TI  - Accuracy of radiography, nuclear scintigraphy, and histopathology for determining
      the proximal extent of distal radius osteosarcoma in dogs.
AB  - OBJECTIVE: To compare the accuracy of radiography, nuclear scintigraphy, and
      histopathology for determining the proximal extent of distal radius osteosarcoma
      in dogs. STUDY DESIGN: Retrospective clinical study. SAMPLE POPULATION: Twenty
      client-owned dogs taken to Colorado State University with osteosarcoma of the
      distal radius. METHODS: Medical records of 20 dogs with confirmed osteosarcoma
      that underwent a limb-salvage procedure were reviewed. Measurements were
      performed directly from the lateral view of each radius, from both the scintigram
      and the radiograph, to determine the length of the radius and the distance from
      the proximal extent of the tumor to the distal radiographic or scintographic
      extent of the radius. The ratio of distal radial involvement to total radius
      length was calculated. A similar ratio was also determined using the macroslide,
      which included the entire portion of bone that was excised during the limb
      salvage procedure. All 3 methods of measurement were compared. RESULTS: Nuclear
      scintigraphy significantly overestimated tumor length when compared with
      macroslide specimen measurements. Radiography also overestimated tumor length,
      but these results were not significantly different from macroslide specimen
      measurements. CONCLUSIONS: Both radiography and nuclear scintigraphy overestimate
      the extent of distal radius osteosarcoma in dogs when compared with
      histopathologic macroslides of the same lesions. Nuclear scintigraphy
      overestimated tumor extent to a larger degree than did radiography. CLINICAL
      RELEVANCE: Although radiography is a more accurate method of measurement of the
      extent of distal radius osteosarcoma, because nuclear scintigraphy overestimates
      tumor length to a greater degree, scintigraphy may provide a larger margin of
      safety for determining the site of proximal osteotomy during a limb-salvage
      procedure. However, caution should be taken when utilizing scintigraphy, because
      this method may overestimate length of radius involved to such an extent as to
      cause the surgeon to believe that a patient is not a suitable limb-salvage
      candidate.

PMID- 11340556
TI  - An in vitro biomechanical comparison of two interlocking-nail systems for
      fixation of ostectomized equine third metacarpal bones.
AB  - OBJECTIVE: To compare the mechanical properties of 2 interlocking-nail systems
      for fixation of ostectomized equine third metacarpi (MC3): (1) a standard
      interlocking nail with 2 parallel screws proximal and distal to a 1-cm ostectomy;
      and (2) a modified interlocking nail with 2 screws proximal and distal to a 1-cm
      ostectomy with the screws offset by 30 degrees. ANIMAL OR SAMPLE POPULATION:
      Twelve pairs of adult equine forelimbs intact from the midradius distally.
      METHODS: Twelve pairs of equine MC3 were divided into 2 test groups (6 pairs
      each): torsion and caudocranial 4-point bending. Standard interlocking nails (6
      hole, 13-mm diameter, 230-mm length) were placed in 1 randomly selected bone from
      each pair. Modified interlocking nails (6-hole, 13-mm, 230-mm length, screw holes
      offset by 30 degrees) were placed in the contralateral bone from each pair. All
      bones had 1-cm mid-diaphyseal ostectomies. Six construct pairs were tested in
      caudocranial 4-point bending to determine stiffness and failure properties. The
      remaining 6 construct pairs were tested in torsion to determine torsional
      stiffness and yield load. Mean values for each fixation method were compared
      using a paired t test within each group. Significance was set at P <.05. RESULTS:
      Mean (+/-SEM) values for the MC3-standard interlocking-nail composite and the MC3
      modified interlocking-nail composite, respectively, in 4-point bending were:
      composite rigidity, 3,119 +/- 334.5 Nm/rad (newton. meter/radian) and 3,185 +/-
      401.2 Nm/rad; yield bending moment, 205.0 +/- 18.46 Nm and 186.7 +/- 6.17 Nm; and
      failure bending moment, 366.4 +/- 21.82 Nm and 378.1 +/- 20.41 Nm. There were no
      significant differences in the biomechanical values for bending between the 2
      fixation methods. In torsion, mean (+/-SEM) values for the MC3-standard
      interlocking-nail composite and the MC3-modified interlocking-nail composite
      were: composite rigidity, 135.5 +/- 7.128 Nm/rad and 112.5 +/- 7.432 Nm/rad; gap
      stiffness, 207.6 +/- 10.57 Nm/rad and 181.7 +/- 12.89 Nm/rad; and yield load,
      123.3 +/- 2.563 Nm and 107.5 +/- 8.353 Nm, respectively. Composite rigidity and
      gap stiffness for standard interlocking-nail fixations were significantly higher
      than the modified interlocking-nail fixation technique in torsion. Yield load had
      a tendency to be higher for the standard interlocking-nail fixation (P =.15).
      CONCLUSIONS: No significant differences in biomechanical properties were
      identified between a standard interlocking nail and one with the screw holes
      offset by 30 degrees in caudocranial 4-point bending. The standard interlocking
      nail was superior to the modified interlocking nail in torsional gap stiffness
      and composite rigidity. The torsional yield load also tended to be higher for the
      standard interlocking nail. CLINICAL RELEVANCE: The standard interlocking nail
      with parallel screw holes is superior to a modified interlocking nail with the
      screw holes offset by 30 degrees in ostectomized equine MC3 bones in vitro when
      tested in torsion.

PMID- 11340557
TI  - Pullout properties of 3.5-mm AO/ASIF self-tapping and cortex screws in a uniform
      synthetic material and in canine bone.
AB  - OBJECTIVES--To compare the pullout properties of 3.5-mm AO/ASIF self-tapping
      screws (STS) to corresponding standard cortex screws (CS) in a uniform synthetic
      test material and in canine femoral bone. The influence of screw-insertion
      technique, test material, and test-material thickness were also assessed. STUDY
      DESIGN--In vitro experimental study. SAMPLE POPULATION--Two independent studies:
      a uniform synthetic test material and paired femurs from mature dogs. METHODS
      Mechanical testing was performed in accordance with standards established by the
      American Society for Testing and Materials for determination of axial pullout
      strength of medical bone screws. Completely inserted STS, completely inserted CS,
      and incompletely inserted STS were tested in 3 groups of 10 test specimens each
      in 4.96-mm and 6.8-mm thick sheets of synthetic material. In the bone study,
      group 1 consisted of 24 completely inserted STS compared with 24 completely
      inserted CS, and group 2 consisted of 24 incompletely inserted STS versus 24
      completely inserted CS. Comparisons were made between paired femurs at
      corresponding insertion sites. Pullout data were normalized, thereby eliminating
      the effect of test-material thickness on pullout properties. Mean values were
      compared using 2-way ANOVA. Statistical significance was set at P <.05. RESULTS-
      In both the 4.96-mm and 6.8-mm synthetic material, pullout testing of the
      completely inserted STS demonstrated significantly greater yield strength and
      ultimate strength than completely inserted CS. There was no significant
      difference between incompletely inserted STS and completely inserted STS. The 6.8
      mm test material significantly increased yield strength and ultimate strength for
      all test groups compared with the 4.96-mm test material. In canine bone, there
      was no significant difference in yield strength of completely inserted STS and
      completely inserted CS. Yield strength of completely inserted STS and completely
      inserted CS were significantly greater than incompletely inserted STS.
      CONCLUSIONS--Pullout properties of completely inserted STS were significantly
      greater than corresponding CS in a uniform test material. In canine bone, the
      pullout strength of STS and CS were not different. Incomplete STS insertion
      resulted in an 18% reduction in holding power as compared with completely
      inserted CS and STS in canine bone. CLINICAL RELEVANCE--The length of STS used in
      canine bone should be such that the cutting flutes extend beyond the trans cortex
      to maximize pullout strength.

PMID- 11340558
TI  - Canine pubic symphysiodesis: investigation of electrocautery dose response by
      histologic examination and temperature measurement.
AB  - OBJECTIVES: To determine thermal necrosis zone and the maximal temperature
      achieved with various electrocautery doses applied to the pubic symphysis of
      immature dogs, and to establish the minimal electrocautery dose needed to affect
      thermal necrosis of the germinal chondrocytes of the immature canine pubis. STUDY
      DESIGN: A randomized, controlled, prospective study. ANIMALS: Twelve puppies, 15
      to 17 weeks of age. METHODS: Each treated puppy was randomly selected to receive
      3 of 33 possible doses of electrical current applied at uniform intervals along
      the pelvic symphysis. Three treatment sites were sham-operated controls. All
      treatment zones were biopsied 7 days after application of electrocautery.
      Confocal laser microscopy with calcein green and ethidium homodimer red stains
      were used to determine cell type and viability within treatment and control
      zones. The physeal diameter and thermal necrosis zone were measured. Thermal
      necrosis zone and dose, and temperature and dose were compared using regression
      analysis. Prediction equation analysis was used to establish dose
      recommendations. RESULTS: Doses of 40 W produced a highly significant linear
      relationship (R(2) =.88, P <.01) with thermal necrosis zone, and a significant
      linear relationship (R(2) =.76, P <.02) with maximal temperature. CONCLUSIONS:
      The thermal necrosis zone within the pelvic symphysis and maximal temperature
      achieved can be reliably predicted using electrocautery doses of 40 W. For
      application of electrocautery to induce pubic symphysiodesis, doses should be
      chosen based on measured or estimated physeal size. Using prediction equation
      analysis, the surgeon can plan mean thermal necrosis zone with acceptable
      variance. CLINICAL RELEVANCE: Unipolar needle electrocautery can be used to
      reliably achieve symphyseal necrosis. Prediction equation analysis can be used to
      determine 40-W doses.

PMID- 11340559
TI  - Expression of transforming growth factor beta(1), beta(3), and basic fibroblast
      growth factor in full-thickness skin wounds of equine limbs and thorax.
AB  - OBJECTIVE: To map the expression of transforming growth factor (TGF)-beta(1), TGF
      beta(3), and basic fibroblast growth factor (bFGF) in full-thickness skin wounds
      of the horse. To determine whether their expression differs between limbs and
      thorax, to understand the pathogenesis of exuberant granulation tissue. STUDY
      DESIGN: Six wounds were created on one lateral metacarpal area and one
      midthoracic area of each horse. Sequential wound biopsies allowed comparison of
      the temporal expression of growth factors between limb and thoracic wounds.
      ANIMALS: Four 2- to 4-year-old horses. METHODS: Wounds were assessed grossly and
      histologically at 12 and 24 hours, and 2, 5, 10, and 14 days postoperatively.
      ELISAs were used to measure the growth factor concentrations of homogenates of
      wound biopsies taken at the same timepoints. RESULTS: TGF-beta(1) peaked at 24
      hours in both locations and returned to baseline in thoracic wounds by 14 days
      but remained elevated in limb wounds for the duration of the study. Expression
      kinetics of TGF-beta(3) differed from those of TGF-beta(1). TGF-beta(3)
      concentrations gradually increased over time, showing a trend toward an earlier
      and higher peak in thoracic compared with limb wounds. bFGF expression kinetics
      resembled those of TGF-beta(1), but no statistically significant differences
      existed between limb and thoracic wounds. CONCLUSIONS: Growth factor expression
      is up-regulated during normal equine wound repair. TGF-beta(1) and TGF-beta(3)
      show a reciprocal temporal regulation. Statistically significant differences
      exist between limb and thoracic wounds with respect to TGF-beta(1) expression.
      CLINICAL RELEVANCE: The persistence of TGF-beta(1) expression in leg wounds may
      be related to the development of exuberant granulation tissue in this location,
      because TGF-beta(1) is profibrotic.

PMID- 11340560
TI  - Effect of tibial plateau leveling on cranial and caudal tibial thrusts in canine
      cranial cruciate-deficient stifles: an in vitro experimental study.
AB  - OBJECTIVES: To investigate the effect of tibial plateau leveling (TPL) on tibial
      subluxation and tibial axial rotation; to determine the minimal tibial plateau
      rotation (MinTPR) angle that provides stifle stability; and to evaluate caudal
      cruciate ligament (CaCL) strain following tibial plateau rotation in cranial
      cruciate ligament (CrCL)-deficient stifles. ANIMALS: Fifteen canine cadaver hind
      limbs. METHODS: Tibial subluxation was measured from lateral radiographs in
      intact, loaded stifles and after sequential CrCL transection, MinTPR, TPL, and
      CaCL transection. The MinTPR angle was determined using a custom-made hinge plate
      and compared with the TPL angle. Tibial axial rotation was evaluated in CrCL
      deficient stifles before and after TPL. Finally, CaCL strain was recorded in
      intact, loaded stifles, and following MinTPR, TPL, and tibial plateau over
      rotation (MaxTPR) using a force probe. RESULTS: Cranial tibial subluxation in
      CrCL-deficient stifles was eliminated with TPL. Tibial plateau rotation, however,
      induced caudal tibial subluxation, which significantly increased from MinTPR to
      TPL before and after CaCL transection. The MinTPR angle was 6.5 degrees +/- 0.9
      degrees less than the TPL angle (P <.05). Tibial internal rotation decreased
      significantly after TPL in CrCL-deficient stifles. Finally, CaCL strain increased
      with increasing tibial plateau rotation. CONCLUSIONS: This study suggests that,
      during stance phase, TPL transforms cranial tibial thrust into caudal tibial
      thrust, thereby stabilizing the stifle in the cranio-caudal plane via the
      constraint of the CaCL. The increase in CaCL stress, which results from tibial
      plateau rotation, could predispose the CaCL to fatigue failure and therefore
      would caution against tibial plateau over-rotation.

PMID- 11340561
TI  - Arthrodesis of the equine proximal interphalangeal joint: a biomechanical
      comparison of three 4.5-mm and two 5.5-mm cortical screws.
AB  - OBJECTIVE: To compare the biomechanical characteristics and mode of failure of 2
      parallel-screw techniques for proximal interphalangeal joint arthrodesis in
      horses. STUDY DESIGN: Randomized block design, blocking for horse (1-5), method
      of screw fixation (three 4.5-mm vs two 5.5-mm), side (left limb vs right limb),
      and end (front limb vs hind limb). Constructs were loaded to failure in 3-point
      bending in a dorsal-to-palmar (plantar) direction. SAMPLE POPULATION: Twenty
      limbs (10 limb pairs) from 5 equine cadavers. METHODS: A combined aiming device
      was used to facilitate consistent screw placement. Three parallel 4.5-mm cortical
      screws were placed in lag fashion in 1 limb of a pair, and 2 parallel 5.5-mm
      cortical screws were placed in lag fashion in the contralateral limb. Arthrodesis
      constructs were tested in 3-point bending in a dorsal-to-palmar (plantar)
      direction using a materials-testing machine. Loading rate was 19 mm/s. Maximal
      bending moment at failure and composite stiffness were obtained from bending
      moment-angular deformation curves. Data were analyzed using ANOVA and chi(2)
      analysis. RESULTS: There were no significant differences in bending moment (P
      >.05, power = 0.8 @ delta = 19%) or composite stiffness (P >.05, power = 0.8 @
      delta = 19%) between the 2 fixation techniques. Higher maximal bending moment was
      found in front limbs than hind limbs, and front limbs with two 5.5-mm screws than
      hind limbs with two 5.5-mm screws. In all cases, constructs completely failed. A
      greater number of 4.5-mm cortical screws failed than 5.5-mm cortical screws.
      CONCLUSIONS-In pastern arthrodesis constructs loaded in 3-point bending, end
      (front limb vs hind limb) affected maximal bending moment at failure of
      constructs. There was no significant effect of horse, treatment, or side on
      maximal bending moment or stiffness. Two 5.5-mm cortical screws should provide a
      surgically simpler pastern arthrodesis than three 4.5-mm cortical screws while
      maintaining similar biomechanical characteristics. CLINICAL RELEVANCE: Three 4.5
      mm screws or two 5.5-mm screws will provide similar biomechanical characteristics
      in bending when performing equine pastern arthrodesis.

PMID- 11340562
TI  - HIV and cancer in Africa.

PMID- 11340563
TI  - A case-control study of human immunodeficiency virus infection and cancer in
      adults and children residing in Kampala, Uganda.
AB  - Uganda offers a unique setting in which to study the effect of human
      immunodeficiency virus-1 (HIV-1) on cancer. HIV-1 is prevalent there, and cancers
      which are known to be HIV-associated, such as Kaposi's sarcoma and Burkitt's
      lymphoma, are endemic. Adults residing in Kampala, Uganda, presenting with cancer
      in city hospitals were interviewed and had an HIV test. Of the 302 adults
      recruited, 190 had cancers with a potentially infectious aetiology (cases). The
      remaining 112 adults with tumours not known to have an infectious aetiology
      formed the control group. In addition, 318 children who were also Kampala
      residents were recruited and tested for HIV: 128 with cancer (cases) and 190 with
      non-malignant conditions (controls). HIV seroprevalence was 24% in adult controls
      and 6% in childhood controls. The odds of HIV seropositivity among cases with
      specific cancers (other than Kaposi's sarcoma in adults) were compared with that
      among controls, using odds ratios (ORs), estimated with unconditional logistic
      regression. All ORs were adjusted for age (<5, 5-14, 15-19, 30-44, 45+) and sex
      and, in adults, also for the number of lifetime sexual partners (1 or 2, 3-9,
      10+). In adults, HIV infection was associated with a significantly (p < 0.05)
      increased risk of non-Hodgkin's lymphoma [OR = 6.2, 95% confidence interval (CI)
      1.9-19.9, based on 21 cases] and conjunctival squamous-cell carcinoma (OR = 10.9,
      95% CI 3.1-37.7, based on 22 cases) but not with cancer at other common sites,
      including liver and uterine cervix. In children, HIV infection was associated
      with a significantly increased risk of Kaposi's sarcoma (OR = 94.9, 95% CI 28.5
      315.3, based on 36 cases) and Burkitt's lymphoma (OR = 7.5, 95% CI 2.8-20.1,
      based on 33 cases) but not with other cancers. The pattern of HIV-associated
      cancers in Uganda is broadly similar to that described elsewhere, but the
      relative frequency of specific cancers, such as conjunctival carcinoma, in HIV
      infected people differs.

PMID- 11340564
TI  - [177Lu-DOTA(0),Tyr3] octreotate for somatostatin receptor-targeted radionuclide
      therapy.
AB  - Receptor-targeted scintigraphy using radiolabeled somatostatin analogs such as
      octreotate is being used with great success to demonstrate the in vivo presence
      of somatostatin receptors on various tumors. A new and promising application for
      these analogs is radionuclide therapy. Radionuclides suitable for this
      application include the Auger electron-emitter (111)In and the beta-emitters
      (90)Y (high energy) and (177)Lu (low energy). We investigated
      [DOTA(0),Tyr(3)]octreotate, labeled with the lanthanide (177)Lu, in
      biodistribution and radionuclide therapy experiments using male Lewis rats
      bearing the somatostatin receptor-positive rat CA20948 pancreatic tumor.
      Biodistribution studies in Lewis rats showed the highest uptake in the rat
      pancreatic CA20948 tumor and sst(2)-positive organs, which include the adrenals,
      pituitary and pancreas, of [(177)Lu-DOTA(0),Tyr(3)]octreotate in comparison with
      (88)Y- and (111)In-labeled analogs. Kidney uptake of [(177)Lu
      DOTA(0),Tyr(3)]octreotate could be reduced by approximately 40% by co-injection
      of 400 mg/kg D-lysine. In radionuclide therapy studies, a 100% cure rate was
      achieved in the groups of rats bearing small (< or =1 cm(2)) CA20948 tumors after
      2 doses of 277.5 MBq or after a single dose of 555 MBq [(177)Lu
      DOTA(0),Tyr(3)]octreotate. A cure rate of 75% was achieved after a single
      administration of 277.5 MBq. In rats bearing larger (> or =1 cm(2)) tumors, 40%
      and 50% cure rates were achieved in the groups that received 1 or 2 277.5 MBq
      injections of [(177)Lu-DOTA(0),Tyr(3)]octreotate, respectively. After therapy
      with [(177)Lu-DOTA(0),Tyr(3)]octreotide in rats bearing small tumors, these data
      were 40% cure after 1 injection with 277.5 MBq and 60% cure after 2 repeated
      injections. In conclusion, [(177)Lu-DOTA(0),Tyr(3)]octreotate has demonstrated
      excellent results in radionuclide therapy studies in rats, especially in animals
      bearing smaller tumors. This candidate molecule shows great promise for
      radionuclide therapy in patients with sst(2)-expressing tumors.

PMID- 11340565
TI  - Helicobacter-induced expression of Bcl-X(L) in B lymphocytes in the mouse model:
      a possible step in the development of gastric mucosa-associated lymphoid tissue
      (MALT) lymphoma.
AB  - Primary gastric mucosa-associated lymphoid tissue (MALT) lymphoma may develop
      from chronic infection with Helicobacter sp. in the mouse model. The mechanisms
      of pathogenesis remain unclear. Regulation of B-cell proliferation and death are
      important features to investigate. Proteins encoded by bcl-2 family genes, e.g.,
      Bcl-X(L), regulate apoptosis; and alterations in the expression of these genes
      can contribute to the development of cancer. Our aim was to determine the role of
      Bcl-X(L) in B lymphocytes in the development of gastric MALT lymphoma associated
      with Helicobacter infection using the BALB/c mouse model. We analyzed 37 animals
      with Helicobacter-associated MALT (n = 25), low-grade MALT lymphoma (n = 10) and
      high-grade lymphoma (n = 2), investigating the in vivo distribution of Bcl-X(L)
      in B cells/B-lymphoma cells using immunohistochemical analysis. In vitro
      cultivation of B cells/B-lymphoma cells was employed to perform RT-PCR analysis
      of Bcl-X(L) mRNA expression after cell stimulation with Helicobacter antigen. We
      found significant Bcl-X(L) protein expression in B lymphocytes within MALT and
      low-grade MALT lymphoma, whereas there was no and minimal expression,
      respectively, of Bcl-X(L) in the 2 high-grade MALT lymphoma cases. Expression of
      bcl-X(L) mRNA in B lymphocytes was up-regulated in vitro upon Helicobacter
      antigen stimulation and associated with prolonged cell survival. These findings
      support the hypothesis that Bcl-X(L) plays a role in the pathogenesis of B-cell
      MALT lymphoma by providing cell-survival signals and by triggering the
      acquisition of MALT.

PMID- 11340566
TI  - AlphaVbeta6 integrin promotes invasion of squamous carcinoma cells through up
      regulation of matrix metalloproteinase-9.
AB  - The integrin alphaVbeta6 is a fibronectin receptor, which is not detectable on
      normal epithelium but is neo-expressed in oral epithelial dysplasia and oral
      squamous-cell carcinoma (SCC), suggesting a role in promoting malignant behaviour
      and tumour progression. We used transfection and retroviral infection to create a
      panel of SCC cell lines expressing various levels of alphaVbeta6 to examine this
      possibility. We found that increased expression of alphaVbeta6 in malignant
      keratinocytes up-regulates MMP-9 and MMP-2 expression and promotes invasion in an
      MMP-9-dependent manner. Our results suggest a possible mechanism for the
      involvement of alphaVbeta6 in squamous carcinoma in vivo.

PMID- 11340567
TI  - Radiation-induced apoptosis in human myeloma cell line increases BCL-2/BAX dimer
      formation and does not result in BAX/BAX homodimerization.
AB  - A popular model of BCL-2 and BAX involvement in apoptosis suggests that upon
      apoptosis induction cytosolic BAX translocates to the mitochondria, where it
      displays the pro-apoptotic function, which involves its homodimerization. BCL-2
      exerts anti-apoptotic function by forming heterodimers with BAX, thus
      neutralizing the pro-apoptotic activity of the latter. We have shown that
      irradiation of the human myeloma cell line RPMI-8226 induced apoptosis as
      determined by DNA degradation, cytochrome c release into cytoplasm and BCL-2
      caspase-mediated cleavage. BCL-2 protein was present only in the membrane
      fraction, whereas BAX was found both in cytosol and membranes isolated from non
      irradiated cells. Radiation induced moderate redistribution of BAX from cytosol
      to membranes with a concomitant increase in BCL-2/BAX heterodimer formation.
      Rapid and transient BCL-2 phosphorylation in membrane fractions of irradiated
      cells did not affect BCL-2/BAX heterodimerization. We failed to detect any
      BAX/BAX homodimers in apoptotic cells. Our findings show that in irradiated RPMI
      8226 cells the formation of BCL-2/BAX heterodimers correlates with apoptosis. We
      conclude that BCL-2/BAX heterodimers are negative regulators of death protection,
      and our data agree with those who propose that BCL-2 does not require BAX to
      exert its survival function.

PMID- 11340568
TI  - Expression of retinoic acid receptor gamma correlates with retinoic acid
      sensitivity and metabolism in head and neck squamous cell carcinoma cell lines.
AB  - Retinoids, analogues of vitamin A, can reverse premalignant lesions and prevent
      second primary tumors in patients with head and neck squamous cell carcinoma
      (HNSCC). The effects of retinoids are mediated by retinoic acid receptors (RARs)
      and retinoid X receptors (RXRs), which act as ligand-activated transcription
      factors. The regulation of cell growth, differentiation and retinoid metabolism
      in normal, premalignant and malignant cells by retinoids is thought to be a
      result of their effects on gene expression. We investigated mRNA expression of
      RARs (alpha, beta, and gamma) and RXR-beta by means of RNase protection and
      related this to retinoic acid (RA)-induced growth inhibition and RA turnover in
      four HNSCC cell lines (UM-SCC-14C, UM-SCC-22A, UM-SCC-35 and VU-SCC-OE). An RA
      resistant subline of UM-SCC-35 was generated by exposure to increasing
      concentrations of RA for 8 months (designated UM-SCC-35R). RA turnover was
      determined on the basis of decreasing RA levels in the cells and culture medium
      after exposure to 1 microM RA. We found that RAR-gamma mRNA expression was
      strongly correlated with RA-induced growth inhibition (p = 0.016, R = 0.92) and
      RA turnover (p = 0.041, R = 0.86). RAR-beta transcript levels were reduced in
      three of five cell lines compared with normal mucosa, and these did not correlate
      with RA-induced growth inhibition and RA turnover. Expression of RAR-alpha and
      RXR-beta was not substantially altered in any of the cell lines. These findings
      suggest that in HNSCC cell lines RAR-gamma is the most important retinoid
      receptor for regulation of RA turnover rate and RA-induced growth inhibition.

PMID- 11340569
TI  - Clinical relevance of microvessel density in laryngeal squamous cell carcinomas.
AB  - The clinical implications of microvessel density (MVD) in head and neck tumors
      have not been fully elucidated. We investigated the clinicopathologic correlates
      and prognostic relevance of MVD in a series of 122 consecutive patients with
      surgically treated laryngeal squamous cell carcinoma followed-up for a mean of 79
      months. MVD was evaluated after CD34 immunostaining in 3 250x microscopic fields
      representative of the "hot spot" area, and expressed as the mean value of the
      vessel counts per millimeter squared. The overall median value of the
      intratumoral vessel count was 69.5/mm(2). In the 20 cases we analyzed, MVD
      increased significantly from normal to dysplastic mucosa and infiltrating
      carcinoma (p = 0.0001). Nineteen carcinomas (15.6%) had MVD values that were
      equal to or lower than the highest MVD value (52.7/mm(2)) observed in normal
      mucosa samples (in which the median MVD count was 34.5/mm(2), range 16.6
      52.7/mm(2), mean 35.1 +/- 11.5/mm(2)) and were therefore considered poorly
      vascularized. Periodic acid-Schiff (PAS) staining revealed intratumoral PAS
      positive connective tissue septa in 13 cases (10.7%). The patients with poorly
      vascularized tumors showed a tendency toward a better prognosis, but the
      anatomical site, tumor extension and clinical stage were the only variables
      significantly associated with disease-free and overall survival.

PMID- 11340570
TI  - Optimization of differential photodynamic effectiveness between normal and tumor
      urothelial cells using 5-aminolevulinic acid-induced protoporphyrin IX as
      sensitizer.
AB  - Photodynamic therapy using 5-aminolevulinic acid (5-ALA)-induced protoporphyrin
      IX is a promising tool in bladder-cancer therapy. However, little is known about
      the cellular mechanisms of phototoxicity. Our aim was to characterize the
      cellular damage and to optimize differential photodynamic effectiveness between
      tumor and normal urothelial cells. RT4 tumor and UROtsa normal urothelial cells
      were used to simulate a papillary bladder tumor in contrast to normal urothelium.
      Photodynamically induced damage in plasma membrane and mitochondria was monitored
      by flow cytometry with propidium iodide exclusion and analysis of aggregate
      formation of the dye JC-1. Cell morphology was investigated by phase-contrast and
      fluorescence microscopy following acridine orange staining. Long incubation times
      (3 hr) led to complete RT4 tumor cell kill accompanied by a marked fraction of
      damaged normal UROtsa cells. Shorter incubation intervals (1 hr) also resulted in
      complete RT4 tumor cell kill; however, most UROtsa cells retained their cell
      properties, including intact plasma membrane and active mitochondria as well as
      intact cellular morphology. Phototoxicity depends not only on cellular sensitizer
      accumulation but also on intracellular localization. Analysis of phototoxic
      mechanisms is an important step for planning combination therapy regimens with,
      e.g., DNA-damaging agents. Further, data indicate that differential phototoxicity
      in normal and tumorous urothelium can be enhanced using differences in cellular
      protoporphyrin IX distribution following short 5-ALA incubation times. These data
      are encouraging for the in vivo situation since short incubation times are a more
      practical approach for local photodynamic therapy of early tumor stages not only
      in the bladder but also, e.g., in the gastro-intestinal tract or bronchial
      mucosa.

PMID- 11340571
TI  - Chromosome 16q deletion and loss of E-cadherin expression in Hodgkin and Reed
      Sternberg cells.
AB  - Hodgkin and Reed-Sternberg (H&RS) cells are generally considered to be the
      neoplastic cells of Hodgkin's disease (HD); however, such H&RS cells are a few in
      number due to the numerous reactive cells. Very few data have so far been
      published on the cytogenetic abnormalities in HD. We have previously used the
      analysis of comparative genomic hybridization (CGH), employing sorted H&RS cells.
      The most commonly observed genetic aberrations were a loss on 16q11/21, a gain on
      1p13 and a gain on 7q35/36. To confirm the loss of 16q, we analyzed the loss of
      heterozygosity (LOH) using the regions D16S3075 (16p13), D16S3068 (16q11),
      D16S3136 (16q12), D16S503 (16q13), D16S515 (16q21), D16S3091 (16q23) and D16S520
      (16q24). A total of 100 sorted H&RS cells were compared with a similar number of
      sorted reactive T cells in 15 cases with HD, including 5 cases with nodular
      sclerosis (NS) type and 10 cases with mixed cellularity (MC) type. LOHs of 16q,
      especially 16q21-23, were frequently detected, but 16p deletions were infrequent.
      Analysis of 16q21 showed LOH in 12 of 15 cases with HD (80%), including 9 cases
      with MC type (90%) and 3 cases with NS type (60%). 16q23 showed LOH in 9 of 15
      cases with HD (60%), including 5 cases with MC type (50%) and 4 cases with NS
      (80%). On the other hand, 16p13 showed LOH in 3 of 15 cases with HD (20%).
      Immunohistochemical staining showed that H&RS cells rarely expressed E-cadherin,
      which is located on 16q. Our findings suggest that 16q deletion, especially 16q21
      23, is probably involved in H&RS giant cell formation and tumorigenesis.

PMID- 11340572
TI  - Impact of genetic polymorphisms of 17-hydroxylase cytochrome P-450 (CYP17) and
      steroid 5alpha-reductase type II (SRD5A2) genes on prostate-cancer risk among the
      Japanese population.
AB  - Steroid hormones, especially testosterone, play important roles in the
      carcinogenesis of prostate cancer, and several studies have reported changes in
      risk with polymorphisms of genes involved in steroid metabolism. One example is
      the CYP17 gene, which has a polymorphic T-to-C substitution in the 5'
      untranslated region giving rise to A1 (T) and A2 (C) alleles. Steroid 5alpha
      reductase type II (SRD5A2), which converts testosterone to the metabolically more
      active dihydrotestosterone, exhibits 2 polymorphisms: V89L, which substitutes
      leucine for valine at codon 89, and A49T, which substitutes threonine for alanine
      at codon 49. We therefore designed a case-control study of 105 prostate-cancer
      patients and 210 controls with benign prostatic hyperplasia for the purpose of
      investigating the association between prostate-cancer risk and polymorphisms in
      the SRD5A2 and CYP17 genes among the Japanese. The frequency of the CYP17 A2/A2
      genotype in cases (18.8%) was higher than in controls (14.5%). Compared with the
      A1/A1 genotype, the odds ratio for the A2/A2 genotype was 2.39 (95% confidence
      interval 1.04-5.46, p = 0.04). The frequency of the SRD5A2 LL genotype in cases
      (29.3%) was also slightly higher than in controls (24.6%), but this was not
      significant. Regarding the A49T polymorphism of SRD5A2, we could not detect the T
      allele in any of the examined samples. These data suggest a significant
      association between the CYP17 polymorphism and prostate-cancer risk among the
      Japanese.

PMID- 11340573
TI  - Adult Burkitt's lymphoma in patients with and without human immunodeficiency
      virus infection in Kenya.
AB  - Prior to the acquired immunodeficiency syndrome (AIDS) epidemic, one or two cases
      of adult Burkitt's lymphoma (BL) were seen annually at the Kenyatta National
      Hospital, the national referral medical center in Nairobi, Kenya. To investigate
      the influence of human immunodeficiency virus (HIV) infection in adult BL in
      Kenya, we conducted a national prevalence survey of all patients 16 years of age
      and older with BL. A systematic review of medical records of all patients
      diagnosed with BL between 1992 and 1996 was performed. The diagnosis of BL was
      based and confirmed on review of pathological material from time of original
      diagnosis. HIV serology was confirmed by enzyme-linked immunosorbent assay
      (ELISA). Twenty-nine adult patients with BL were identified during the 5-year
      study period. Of these patients, 17 (59%) were males, 12 (41%) were females, and
      the median age was 26 years. Nineteen patients (66%) with BL were HIV
      seropositive. The proportion of men was similar in HIV-seropositive and 
      seronegative patients (58% vs 60%). HIV-seropositive BL patients were
      significantly older than seronegatives (median 35 vs 19.5 years, p < 0.001). HIV
      seropositive patients uniformly presented with constitutional or B symptoms and
      advanced BL accompanied by diffuse lymph node involvement, whereas the clinical
      presentation of HIV-seronegative patients during this time period was reminiscent
      of the "typical" endemic pattern of disease with complete sparing of peripheral
      lymph nodes. The overall survival of HIV-seropositive cases was significantly
      worse than that of the HIV-seronegative cases; median survival in the HIV
      seropositive patients was 15 weeks. There is an approximate 3-fold increase in
      the incidence of adult BL during the time period of this study, which is
      attributable to the AIDS epidemic. In this setting, patients often present with
      disseminated disease, diffuse peripheral lymphadenopathy and fever, the latter
      two of which heretofore have been commonly associated with non
      lymphoproliferative disorders such as Mycobacterium tuberculosis and sexually
      transmitted diseases in Kenya. These observations warrant inclusion of AIDS
      related BL in the differential diagnosis of the adult patient with unexplained
      fever and lymphadenopathy in Kenya. The corollary is that HIV infection is
      virtually excluded in an adult patient without peripheral lymphadenopathy and
      biopsy-proven BL.

PMID- 11340574
TI  - Expression of HLA class I, beta(2)-microglobulin, TAP1 and IL-10 in Epstein-Barr
      virus-associated nasal NK/T-cell lymphoma: Implications for tumor immune escape
      mechanism.
AB  - Several mechanisms of immune escape might be in operation in Epstein-Barr virus
      (EBV)-associated nasal NK/T-cell lymphoma. We have previously shown the
      downregulation of the immunogenic EBV nuclear antigens by alternative promoter
      usage and the preferential selection of the deletion genotype of latent membrane
      protein 1 in nasal lymphoma. To understand further the strategies used for immune
      escape by this tumor, we examined by immunohistochemistry HLA class I expression
      in 15 cases using frozen sections, along with beta(2)-microglobulin and
      transporter associated with antigen processing 1 (TAP1) expression in 39 cases
      using paraffin sections. All nasal NK/T-cell lymphomas showed positive staining
      for HLA class I, beta(2)-microglobulin and TAP1 on most tumor cells, except for
      two cases (5%) in which most of the tumor cells lacked beta(2)-microglobulin
      staining. We next immunostained for interleukin-10 on frozen sections in 13
      cases, all of which showed strong expression by most tumor cells. Transcription
      of human interleukin-10 but not EBV BCRF1 (viral interleukin-10) was identified
      by reverse transcriptase-polymerase chain reaction in these nasal NK/T-cell
      lymphomas. Overall, our data suggest that global downregulation of HLA class I or
      TAP1 rarely accounts for the ability of nasal NK/T-cell lymphoma to evade
      immunosurveillance and that other immune escape mechanisms may be operating in
      nasal NK/T-cell lymphoma, such as production of interleukin-10 to suppress the
      local immune response.

PMID- 11340575
TI  - NK cells are essential for effective BCG immunotherapy.
AB  - Adjuvant intravesical bacillus Calmette-Guerin (BCG) therapy is a well
      established and successful adjuvant immunotherapy in the treatment of superficial
      bladder cancer. Although the function of natural killer (NK) cells in other
      immunotherapeutic regimens (e.g., lymphokine-activated killer [LAK] cell or
      interleukin-2 [IL-2] therapy) has been established, the contribution of NK cells
      to effective BCG immunotherapy is not clear. We used a human in vitro system to
      analyze the role of NK cells in BCG-induced cellular cytotoxicity. After
      stimulation of mononuclear cells with BCG for 7 days, these BCG-activated killer
      (BAK) cells displayed substantial cytotoxicity against bladder tumor cells.
      Magnetic depletion experiments and fluorescence activated cell sorting revealed
      that NK cells were the major effector cell population. To address NK cell
      function in vivo, we studied a syngeneic orthotopic murine bladder cancer model
      and compared BCG immunotherapy in C57BL/6 wild-type mice, NK-deficient beige mice
      and mice treated with anti-NK1.1 monoclonal antibody. Four weekly instillations
      of viable BCG significantly prolonged survival in wild-type mice compared with
      control mice treated with solvent alone. In contrast, BCG therapy was completely
      ineffective in NK-deficient beige mice and in mice treated with anti-NK1.1
      monoclonal antibody. These findings suggest a key role for NK cells during BCG
      immunotherapy.

PMID- 11340576
TI  - Evaluation of peptide vaccine immunogenicity in draining lymph nodes and
      peripheral blood of melanoma patients.
AB  - Many peptide epitopes for cytotoxic T lymphocytes (CTLs) have been identified
      from melanocytic differentiation proteins. Vaccine trials with these peptides
      have been limited mostly to those associated with HLA-A2, and immune responses
      have been detected inconsistently. Cases of clinical regression have been
      observed after peptide vaccination in some trials, but melanoma regressions have
      not correlated well with T-cell responses measured in peripheral blood
      lymphocytes (PBLs). We vaccinated stage IV melanoma patients with a mixture of
      gp100 and tyrosinase peptides restricted by HLA-A1 (DAEKSDICTDEY), HLA-A2
      (YLEPGPVTA and YMDGTMSQV) and HLA-A3 (ALLAVGATK) in an emulsion with GM-CSF and
      Montanide ISA-51 adjuvant. CTL responses were assessed in PBLs and in a lymph
      node draining a vaccine site (sentinel immunized node, SIN). We found CTL
      responses to vaccinating peptides in the SIN in 5/5 patients (100%). Equivalent
      assays detected peptide-reactive CTLs in PBLs of 2 of these 5 patients (40%).
      CTLs expanded from the SIN lysed melanoma cells naturally expressing tyrosinase
      or gp100. We demonstrated immunogenicity for peptides restricted by HLA-A1 and 
      A3 and for 1 HLA-A2 restricted peptide, YMDGTMSQV. Immune monitoring of clinical
      trials by evaluation of PBLs alone may under-estimate immunogenicity; evaluation
      of SIN provides a new and sensitive approach for defining responses to tumor
      vaccines and correlating these responses with clinical outcomes. This combination
      of an immunogenic vaccine strategy with a sensitive analysis of CTL responses
      demonstrates the potential for inducing and detecting anti-tumor immune responses
      in the majority of melanoma patients.

PMID- 11340577
TI  - Adenovirus-mediated gene therapy for bladder cancer in an orthotopic model using
      a dominant negative H-ras mutant.
AB  - It has been suggested that abnormal Ras function is important in the
      carcinogenesis and progression of bladder cancer. Our aim was to investigate the
      efficacy of transurethral inoculation of an adenovirus expressing the dominant
      negative H-ras mutant N116Y against orthotopically implanted human bladder-cancer
      cells in nude mice. We used a replication-defective adenovirus vector containing
      the beta-galactosidase gene (AdCMV-LacZ) as a control and the N116Y gene (AdCMV
      N116Y) as the therapeutic vector under the transcriptional control of the
      cytomegalovirus promoter. We initially investigated the in vitro growth
      suppressive effects of AdCMV-N116Y on 2 human bladder-cancer cell lines, KU-7 and
      UMUC-2. Thereafter, we examined the inhibitory effects of AdCMV-N116Y on the 2
      orthotopically implanted cell lines in nude mice. Intravesically created,
      orthotopic human bladder cancers were established in female KSN athymic nude mice
      with 1x 10(7) cancer cells. Then, 2, 3 and 4 days following implantation, 1 x
      10(9) pfu of AdCMV-LacZ or AdCMV-N116Y were administered transurethrally. In
      vitro growth assays revealed significant growth suppression (>95%) with apoptosis
      of target cells treated with AdCMV-N116Y compared to AdCMV-LacZ. Transurethral
      inoculation of AdCMV-N116Y into the bladder brought about a significant reduction
      in size (73% to 90%) and number (47% to 78%) of orthotopically implanted human
      bladder tumors compared to AdCMV-LacZ or PBS. Normal mucosa in nude mice had
      minor inflammation with the infiltration of mononuclear cells. Our results
      suggest that gene therapy via transurethral inoculation of AdCMV-N116Y holds
      promise for the treatment of human bladder cancer.

PMID- 11340578
TI  - Pre-clinical evaluation of a methotrexate-albumin conjugate (MTX-HSA) in human
      tumor xenografts in vivo.
AB  - Methotrexate covalently bound to human serum albumin in a 1:1 molar ratio (MTX
      HSA) is a new macromolecular drug which is currently being studied in phase I
      clinical trials by the German Association for Medical Oncology (AIO) Phase I/II
      study group. Previous studies have shown that MTX-HSA differs favorably from
      unbound MTX in terms of plasma half-life time, tumor accumulation of albumin and
      uptake mechanisms into cancer cells. To achieve optimal drug efficacy, repeated
      treatment cycles were necessary. To evaluate the anti-tumor activity of MTX-HSA
      and MTX in pre-clinical in vivo models, we selected 7 solid human tumor
      xenografts growing s.c. in nude mice and administered drug either i.p. or i.v.
      weekly for 3 weeks. The maximal tolerated dose (MTD) of MTX-HSA in nude mice was
      12.5 mg/kg given i.p. on days 1, 8 and 15, whereas the MTD for free MTX was 100
      mg/kg given i.v. MTX-HSA was significantly more active (p > 0.01) than MTX in 3
      models. In the soft tissue sarcoma SXF 1301, MTX-HSA effected complete
      remission/cure after a single injection, whereas free MTX resulted in short
      lasting, partial tumor regression. In the prostate-cancer model PRXF PC3M, MTX
      HSA produced growth inhibition of 92.8% of control or an optimal test/control
      (T/C) of 7.2% compared to a T/C of 20.8% for MTX (p = 0.05). In the osteosarcoma
      model SXF 1410, optimal T/C values were 10.2% and 14.5%, respectively (p =
      0.025). In lung cancers LXFE 409 and LXFL 529, bladder cancer BXF 1258 and breast
      cancer MAXF 449, both compounds were inactive. The improved therapeutic effects
      seen in 3 xenograft models under MTX-HSA treatment are promising and might be due
      to specific accumulation of the compound in solid tumors owing to their enhanced
      permeability and retention effect. Thus, clinical development of MTX-HSA will
      continue and sarcomas as well as prostate cancers will be included as potential
      target tumors for upcoming clinical phase II trials.

PMID- 11340579
TI  - Fusion proteins of B7.1 and a carcinoembryonic antigen (CEA)-specific antibody
      fragment opsonize CEA-expressing tumor cells and coactivate T-cell immunity.
AB  - Genetic engineering can be used to generate antigen-specific molecules for
      improved tumor immunotherapy. We have constructed genes coding for fusion
      proteins consisting of a high-affinity antibody single-chain antibody fragment
      (scFv) specific for the human carcinoembryonic antigen (CEA) and the
      costimulation domain of the murine B7.1 molecule (mB7.1) linked to the antibody
      moiety by an IgG3 peptide linker. The hybrid genes were constructed in 2
      orientations, one with the scFv located N-terminal to mB7.1 and one vice versa.
      Soluble proteins were expressed by CHO cells, purified using anti-idiotype
      affinity chromatography and characterized by tumor-cell binding and costimulation
      activity. When tumor cells expressing CEA on the cell membrane were opsonized
      with the CEA-specific costimulators, both fusion proteins specifically stimulated
      murine T-cell preparations to proliferate in a similar manner. Our data suggest
      that "costimulation coating" of tumor cells may be a suitable approach for
      activation of a sustained cellular antitumor response. It also provides the
      opportunity to increase tumor immunogenicity using easily generated soluble
      fusion proteins that advantageously link biological functions of both the humoral
      and the cellular arm of the specific immune system.

PMID- 11340580
TI  - Oncostatic activity of a thiazolidinedione derivative on human androgen-dependent
      prostate cancer cells.
AB  - Thiazolidinedione derivatives with potent antiarthritic activity, such as CGP
      52608, have been suggested to exert their biological effects through the
      activation of the orphan nuclear receptor RORalpha. Since response elements for
      this receptor are present in the promoter region of cell cycle-related genes
      (i.e., p21(WAF1/CIP1) and cyclin A), we reasoned that CGP 52608 might affect cell
      proliferation, cell cycle progression and the expression of cell cycle-related
      genes. This hypothesis has been verified in the human androgen-dependent prostate
      cancer cell line LNCaP. We found that the treatment of LNCaP cells with CGP 52608
      brings about a significant and dose-dependent decrease of cell proliferation.
      Thiazolidinedione affected cell cycle distribution, inducing an accumulation of
      the cells in the G0/G1 phase and a decrease in the S phase. This effect was
      accompanied by an increased expression of the cyclin-dependent kinase inhibitor
      p21(WAF1/CIP1) and a decreased expression of cyclin A. These data indicate that,
      in human androgen-dependent LNCaP prostate cancer cells, the thiazolidinedione
      derivative CGP 52608 exerts a strong cytostatic activity, by reducing cell
      proliferation and by affecting cell cycle distribution through the modulation of
      the expression of cell cycle-related genes. These biological actions of CGP 52608
      might be mediated by the activation of the orphan nuclear RORalpha receptor,
      which is expressed in LNCaP cells.

PMID- 11340581
TI  - A role for loss of p53 function in sensitivity of ovarian carcinoma cells to
      taxanes.
AB  - Loss of p53 function has been linked to increased responsiveness to taxane
      treatment of ovarian carcinoma in clinical studies. We recently reported that the
      acquisition of cisplatin resistance in an ovarian carcinoma cell line (IGROV-1)
      was associated with mutation of p53 and collateral sensitivity to paclitaxel. The
      increased sensitivity to paclitaxel of the cisplatin-resistant subline appeared
      to be pharmacologically relevant since it was reflected in an in vivo
      sensitization to taxanes. To investigate the cellular and molecular basis of this
      phenomenon, we performed a comparative study of cellular response to taxanes
      (paclitaxel and the novel analog IDN 5109) in the parental cell line, containing
      wild-type p53 and its cisplatin-resistant p53 mutant subline (IGROV-1/Pt1). IDN
      5109 was included in this study because of its higher potency and efficacy
      compared with paclitaxel on both tumor systems. The pattern of cellular response
      of the two ovarian cell lines was different. In IGROV-1 cells, apoptosis was an
      early event consequent to a transient mitotic arrest. The cell death of IGROV
      1/Pt1 cells was a somewhat slow and delayed event, following mitotic arrest and
      appearance of hyperploid cells. The increased cytotoxic effect of IDN 5109,
      compared with paclitaxel, was associated with more marked p34(cdc2)
      dephosphorylation in IGROV-1 cells and higher Bcl-2 phosphorylation in IGROV
      1/Pt1 cells after 24 hr of treatment. In each cell line, these biochemical events
      were not correlated with parallel levels of mitotic cells. Attempts to
      reintroduce wild-type p53 in IGROV-1/Pt1 were unsuccessful. However, in other p53
      deficient cells (osteosarcoma SAOS), taxane treatment was associated with
      hyperploid progression and the introduction of wild-type p53 resulted in a
      reduced sensivity. Although our approach does not allow definitive conclusions,
      these results suggest that loss of p53-dependent post-mitotic checkpoint results
      in a different time-course of taxane-induced cell death following DNA
      reduplication. These events, more evident after exposure to the potent analog IDN
      5109, support the notion that the enhanced sensitivity of p53 mutant cells is
      closely related to the different mode of cell death.

PMID- 11340582
TI  - Selection of peptides and synthesis of pentameric peptabody molecules reacting
      specifically with ErbB-2 receptor.
AB  - The HER-2/ErbB-2 oncoprotein is overexpressed in human breast and ovarian
      adenocarcinomas and is clearly associated with the malignant phenotype. Although
      no specific ligand for this receptor has been positively identified, ErbB-2 was
      shown to play a central role in a network of interactions with the related ErbB
      1, ErbB-3 and ErbB-4 receptors. We have selected new peptides binding to ErbB-2
      extracellular domain protein (ECD) by screening 2 newly developed constrained and
      unconstrained random hexapeptide phage libraries. Out of 37 phage clones, which
      bound specifically to ErbB-2 ECD, we found 6 constrained and 10 linear different
      hexapeptide sequences. Among the latter, 5 consensus motifs, all with a common
      methionine and a positively charged residue at positions 1 and 3, respectively,
      were identified. Furthermore, 3 representative hexapeptides were fused to a
      coiled-coil pentameric recombinant protein to form the so-called peptabodies
      recently developed in our laboratory. The 3 peptabodies bound specifically to the
      ErbB-2 ECD, as determined by enzyme-linked immunosorbent assay and BIAcore
      analysis and to tumor cells overexpressing ErbB-2, as shown by flow cytometry.
      Interestingly, one of the free selected linear peptides and all 3 peptabodies
      inhibited the proliferation of tumor cells overexpressing ErbB-2. In conclusion,
      a novel type of ErbB-2-specific ligand is described that might complement
      presently available monoclonal antibodies.

PMID- 11340583
TI  - Quantification of angiogenesis stimulators in children with solid malignancies.
AB  - Humoral angiogenesis stimulators including vascular endothelial growth factor
      (VEGF) and basic fibroblast growth factor (bFGF) have been implicated in the
      pathogenesis of solid malignancies. However, it has remained unclear whether both
      stimulators contribute to the development and progression of solid malignancies
      of children. The aim of the present study was to determine whether VEGF and bFGF
      are elevated in body fluids of children with solid malignancies and, if so,
      whether these elevated levels correlate with clinical parameters. Using enzyme
      linked immunosorbent assays (ELISAs), we quantified VEGF and bFGF in serum (n =
      107) and urine (n = 57) of healthy children and of children with solid
      malignancies (serum: n(VEGF) = 69, n(bFGF) = 60; urine: n(VEGF) or n(bFGF) = 13).
      Finally, we compared patients' pre-therapeutic and post-therapeutic levels. Serum
      VEGF was elevated in children with several solid tumors (Ewing's sarcoma,
      primitive neuroectodermal tumours, malignant lymphoma, Langerhans cell
      histiocytosis and medulloblastoma). In contrast, serum bFGF, urinary bFGF or
      urinary VEGF were not significantly elevated. Upon successful therapy, elevated
      pre-therapeutic serum VEGF levels declined to levels present in healthy children.
      VEGF could contribute to the progression of pediatric solid malignancies, and
      serum VEGF could be used to monitor therapeutic response. Furthermore, the
      determination of angiogenesis stimulators could identify patients eligible for
      anti-angiogenic therapy.

PMID- 11340584
TI  - In vivo documentation of photochemical internalization, a novel approach to site
      specific cancer therapy.
AB  - Photochemical internalization (PCI) is a unique procedure for site-specific
      delivery of several types of membrane-impermeable molecules to the cytosol of
      target cells. The technology is based on photochemical-induced release of
      endocytosed macromolecules from endosomes and lysosomes into the cytosol. The
      purpose of this study was to evaluate the therapeutic potential of PCI of the
      type I ribosomal-inactivating protein gelonin in an animal model. The
      photosensitizer aluminum phthalocyanine disulfonate (AlPcS(2a)) was injected
      intraperitoneally (10 mg/kg) into athymic female BALB/c (nu/nu) nude mice (8-9
      mice per group) with subcutaneously growing human adenocarcinoma (WiDr) tumors 48
      hr before exposure to 135 J/cm(2) of red light focused on the tumor. Six hours
      before light exposure a single dose of 50 microg gelonin was administrated
      intratumorally. Tumor growth was measured at least twice a week. After
      immunomagnetic separation of in vivo growing tumor cells the subcellular
      localization of the photosensitizer was evaluated by fluorescence microscopy. The
      photosensitizer localized in endocytic vesicles in in vivo growing WiDr cells.
      Furthermore, it was found that in vitro gelonin treatment of WiDr cells isolated
      from photosensitizer-treated mice potentiated a light-induced decrease of clonal
      survival. Complete remission in 6 of 9 (67%) of the treated mice were induced.
      Our findings indicate that photochemical treatment with the photosensitizer
      AlPcS(2a) activates the cytotoxic potential of gelonin in vivo. These results
      demonstrate that the synergistic effect of combining photoactivation of
      photosensitizer located in endocytic vesicles and gelonin is indeed a result of
      PCI of gelonin.

PMID- 11340585
TI  - Types of dietary fat and breast cancer: a pooled analysis of cohort studies.
AB  - Recently, there has been interest in whether intakes of specific types of fat are
      associated with breast cancer risk independently of other types of fat, but
      results have been inconsistent. We identified 8 prospective studies that met
      predefined criteria and analyzed their primary data using a standardized
      approach. Holding total energy intake constant, we calculated relative risks for
      increments of 5% of energy for each type of fat compared with an equivalent
      amount of energy from carbohydrates or from other types of fat. We combined study
      specific relative risks using a random effects model. In the pooled database,
      7,329 incident invasive breast cancer cases occurred among 351,821 women. The
      pooled relative risks (95% confidence intervals [CI]) for an increment of 5% of
      energy were 1.09 (1.00-1.19) for saturated, 0.93 (0.84-1.03) for monounsaturated
      and 1.05 (0.96-1.16) for polyunsaturated fat compared with equivalent energy
      intake from carbohydrates. For a 5% of energy increment, the relative risks were
      1.18 (95% CI 0.99-1.42) for substituting saturated for monounsaturated fat, 0.98
      (95% CI 0.85-1.12) for substituting saturated for polyunsaturated fat and 0.87
      (95% CI 0.73-1.02) for substituting monounsaturated for polyunsaturated fat. No
      associations were observed for animal or vegetable fat intakes. These
      associations were not modified by menopausal status. These data are suggestive of
      only a weak positive association with substitution of saturated fat for
      carbohydrate consumption; none of the other types of fat examined was
      significantly associated with breast cancer risk relative to an equivalent
      reduction in carbohydrate consumption.

PMID- 11340586
TI  - Time- and depth-dependent changes in crosslinking and oxidation of shelf-aged
      polyethylene acetabular liners.
AB  - Since crosslinking and oxidation of ultrahigh-molecular-weight polyethylene
      (UHMWPE) have important roles in determining the wear resistance of UHMWPE total
      joint components, the time and depth dependence of crosslinking and oxidation of
      new shelf-aged (2-11 years), ready-to-implant acetabular liners were studied by
      using solvent extraction and Fourier transform infrared spectroscopy. The
      ultrastructure of these materials also was examined by using low-voltage scanning
      electron microscopy in an oil-free vacuum. Oxidation levels increased with time
      and with depth (p < 0.0001) from the surface of the older liners to a maximum
      value at about 1-2 mm below the surface, then decreased. They were minimal at the
      midsection of the liners. The crosslinking of these liners decreased with time
      and depth (p < 0.0001) and was inversely proportional to the level of oxidation.
      High and depth-dependent oxidation levels were observed in all older liners made
      from GUR 415 and 412 resins but were distinctly absent from a comparably aged
      (i.e., 9 years) liner made from 1900 CM-resin. Some liners showed varying degrees
      of inhomogeneous and discontinuous morphologic ultrastructure in addition to
      varying amounts of porosity while others had a more homogeneous ultrastructure.
      Oxidation and crosslinking of polyethylene are time- and depth-dependent
      processes that are mutually competitive. We suggest that resin choice and perhaps
      consolidation-related variables lead to differences in polyethylene's
      ultrastructure. These ultrastructural differences in polyethylene's
      inhomogeneities, that is, the type (interconnected or closed-cell) or extent may
      affect the oxidation resistance of polyethylene. While oxygen diffusion to free
      radicals in polyethylene already is known to explain some of these time- and
      depth-dependent effects, perhaps such ultrastructural variations also may
      facilitate or retard oxygen diffusion in this material. Resin-based
      ultrastructural variability partially may explain the variability in the clinical
      performance of polyethylene total joint implant components. Thus resin choice or
      processing modifications related to polyethylene's ultrastructure may increase
      its oxidation resistance and ultimately improve the clinical wear performance of
      polyethylene total joint orthopedic implants.

PMID- 11340587
TI  - Osteoclast induction from bone marrow cells is due to pro-inflammatory mediators
      from macrophages exposed to polyethylene particles: a possible mechanism of
      osteolysis in failed THA.
AB  - Polyethylene debris from joint replacements may be transported in synovial fluid
      and be phagocytosed by macrophages. The activation and migration of macrophages
      may play important roles in osteolysis and implant loosening. Tissues from the
      bone-implant interface do not always contain wear debris, which may mean that
      osteolysis may not require direct contact with wear debris. We hypothesized that
      the release of polyethylene debris from the implants induces macrophage
      activation in the joint space. Then the activated macrophages release humoral
      factors, such as inflammatory cytokines, into the joint fluid. These cytokines
      may be transported to the bone marrow tissues around the implants where they
      stimulate the differentiation of the bone marrow cells into osteoclasts. Finally,
      the activated osteoclasts resorb the surrounding bone. To test this hypothesis,
      macrophages were stimulated by polyethylene particles. The levels of interleukin
      6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were determined by enzyme
      linked immunosorbent assay and were increased significantly. To test humoral
      interaction between macrophages and bone-marrow cells, a co-culture system was
      used in an in vitro model. With this system, two kinds of cells can be cultured
      together with humoral contact without the two cell types having to contact each
      other. We stimulated the macrophages with 5 microm of polyethylene particles and
      observed whether the bone marrow cells differentiated into the osteoclasts
      without contact with the macrophages. The numbers of osteoclasts were assessed
      using tartrate-resistant acid phosphatase (TRAP) staining. The numbers of TRAP
      positive cells in the polyethylene particle-stimulated group were higher than in
      the control group. The ability of the TRAP-positive cells to resorb bone was
      confirmed by dentine pit formation assay. The results of this study support our
      hypothesis and suggest that one mechanism of osteolysis in failed joint
      arthroplasty is the more distant effects of pro-inflammatory cytokine release on
      osteoclast differentiation and/or activity.

PMID- 11340588
TI  - Transient electric fields induced by mechanically assisted corrosion of Ti-6Al
      4V.
AB  - Samples of Ti-6Al-4V were immersed in physiological solution and abraded via an
      electrochemical scratch method to observe the development of transient electric
      fields a finite distance from the scratch event. Transient electric fields were
      detected near both potentiostatically held and freely corroding samples.
      Transient currents measured by a potentiostatically held PtIr microelectric probe
      near a potentiostatically held sample were opposite in sign to those of the
      mechanically induced sample currents and were found to change character with
      sample potential, probe potential, and distance from the scratch event. Transient
      probe currents measured near a freely corroding sample were of the opposite sign
      as the sample transient near the primary site of oxidation, but were of the same
      sign near the primary site of reduction. The measured transients are a direct
      result of the electrochemical processes ongoing during oxide fracture and
      repassivation and can be sensed several millimeters remote from the abrasion
      site. A model for the generation of these fields is presented. Possible effects
      that these potentials may have on cellular structures surrounding an implant are
      proposed.

PMID- 11340589
TI  - Modulation of epithelial tissue and cell migration by microgrooves.
AB  - We used a polystyrene substratum to study the response of migrating epithelium to
      1- or 5-microm depth microgrooves with groove/ridge widths of 1, 2, 5, or 10
      microm. The migration of a tissue sheet was enhanced along the microgrooves,
      while migration across the microgrooves was inhibited. Changing the depth of the
      microgrooves had a greater effect on migration than alteration of the
      groove/ridge width. The migration of epithelial cells from a confluent monolayer
      culture followed a similar pattern to that of intact epithelial tissue. Cellular
      extensions generally followed the microgroove direction by tracking along the top
      of the ridges or following the ridge walls, as revealed by scanning electron
      microscopy. Actin filaments within the basal cell layer of the tissue were
      aligned with the microgrooves, unlike filaments in the superficial layers that
      did not appear to be affected by the presence of underlying microgrooves. The
      basal cell layer of the tissue conformed to the contours of the microgroove
      following migration. However, the ultrastructure of the tissue above the ridges
      resembled that of tissue on a flat surface. We concluded that surface
      microgrooves have the potential to direct the migration of immediately adjacent
      epithelial tissue, the effect of which is to guide epithelial tissue on the
      surface of implanted biomaterials.

PMID- 11340590
TI  - Osteoclastic resorption of biomimetic calcium phosphate coatings in vitro.
AB  - A new biomimetic method for coating metal implants enables the fast formation of
      dense and homogeneous calcium phosphate coatings. Titanium alloy (Ti6Al4V) disks
      were coated with a thin, carbonated, amorphous calcium phosphate (ACP) by
      immersion in a saturated solution of calcium, phosphate, magnesium, and
      carbonate. The ACP-coated disks then were processed further by incubation in
      calcium phosphate solutions to produce either crystalline carbonated apatite (CA)
      or octacalcium phosphate (OCP). The resorption behavior of these three biomimetic
      coatings was studied using osteoclast-enriched mouse bone-marrow cell cultures
      for 7 days. Cell-mediated degradation was observed for both carbonated apatite
      and octacalcium phosphate coatings. Numerous resorption lacunae characteristic of
      osteoclastic resorption were found on carbonated apatite after cell culture. The
      results showed that carbonated apatite coatings are resorbed by osteoclasts in a
      manner consistent with normal osteoclastic resorption. Osteoclasts also degraded
      the octacalcium phosphate coatings but not by classical pit formation.

PMID- 11340591
TI  - Sustained release of basic fibroblast growth factor and angiogenesis in a novel
      covalently crosslinked gel of heparin and alginate.
AB  - The construction of organs by tissue engineering and regenerative engineering,
      using an artificial extracellular matrix, is an innovative method that is
      expected to replace artificial organs and organ transplantation. We have produced
      an artificial extracellular matrix of alginate and demonstrated that the matrix
      stimulated the regeneration of skin, nerve, and bone. In this report, the new
      matrix, which consists of heparin and alginate covalently crosslinked with
      ethylenediamine, was produced to stabilize and control the release of growth
      factors. Heparin content of the new matrix was confirmed by toluidine blue
      absorption, elementary analysis, and Fourier transform infrared spectrum. In
      vitro experiments showed that the new matrix significantly suppressed the initial
      burst of basic fibroblast growth factor, which is a representative member of
      heparin-binding growth factors, and released biologically active basic fibroblast
      growth factor for 1 month under physiological conditions. Obvious cellular
      infiltration and angiogenesis were shown to occur in the new matrix which was
      implanted subcutaneously in the dorsal area of rat with 1 microg of basic
      fibroblast growth factor for 2 weeks. This new matrix may be useful for not only
      the construction of transplantable blood vessels of small diameter, but also the
      induction of angiogenesis in regenerated skin constructed by tissue engineering.

PMID- 11340592
TI  - A comparison of the adhesion of mammalian cells and Staphylococcus epidermidis on
      fibronectin-modified polymer surfaces.
AB  - The modification of polymer surfaces to mimic the extracellular matrix, and
      therefore, stimulate cell growth via receptor-mediated interactions, is one
      approach used to promote the integration of tissue-engineering scaffolds and
      biomaterials into the body. However, by optimizing surfaces for tissue
      integration it is likely that bacterial adhesion may also be affected, resulting
      in a greater risk of biomaterial-related infection. This could be detrimental to
      both the implant and the patient because biomaterial related infections are
      particularly resistant to host defenses and antibiotics. In this study, we
      analyzed the adhesion of a Staphylococcus epidermidis clinical isolate and 3T3
      rat fibroblasts to tissue culture plastic coated with varying concentrations of
      fibronectin (Fn). Bacterial adhesion was always lower than tissue culture plastic
      and appeared to decrease with increasing Fn concentrations. Mammalian cell
      adhesion to Fn exceeded adhesion to tissue culture plastic but did not differ
      significantly over the range of protein concentrations or between 1 and 4 h of
      incubation. In most cases, the total surface coverage did not vary with time or
      Fn concentration, indicating that maximal cell adhesion and spreading occurred
      rapidly and at low protein concentrations. This study suggests that, by
      controlling the density of proteins or ligands on a surface, we can potentially
      optimize mammalian cell adhesion without stimulating bacterial adhesion, hence
      reducing the likelihood of infection.

PMID- 11340593
TI  - Degradable and injectable poly(aldehyde guluronate) hydrogels for bone tissue
      engineering.
AB  - Degradable and injectable hydrogels may be ideal for bone-tissue engineering,
      especially in the craniofacial region because of the ease of access for
      injection. Alginate hydrogels potentially could be used as injectable cell
      delivery vehicles, but they exhibit a limited range of mechanical properties and
      uncontrollable disintegration time. Therefore we synthesized new hydrogels,
      composed of poly(aldehyde guluronate) (PAG) and adipic acid dihydrazide, that
      have a wide range of mechanical stiffness and controllable degradation rate.
      MC3T3-E1 cells adhered and multiplied on PAG hydrogels in vitro. When primary rat
      calvarial osteoblasts were mixed with PAG hydrogels and subcutaneously injected
      into the backs of mice, mineralized bone tissues were formed 9 weeks following
      implantation. These hydrogels may find wide utility as an injectable delivery
      system for bone precursor cells as well as for other applications in tissue
      engineering.

PMID- 11340595
TI  - Comparison of three joint simulator wear debris isolation techniques: acid
      digestion, base digestion, and enzyme cleavage.
AB  - Quantification of ultrahigh molecular weight polyethylene (UHMWPE) wear debris
      remains a challenging task in orthopedic device analysis. Currently, the weight
      loss method is the only accepted practice for quantifying the amount of wear
      generated from a PE component. This technique utilizes loaded soak controls and
      weight differences to account for polymeric material lost through wear
      mechanisms. This method enables the determination of the amount of wear in the
      orthopedic device, but it provides no information about debris particulate size
      distribution. In order to shed light on wear mechanisms, information about the
      wear debris and its size distribution is necessary. To date, particulate
      isolation has been performed using the base digestion technique. The method uses
      a strong base, ultracentrifugation, and filtration to digest serum constituents
      and to isolate PE debris from sera. It should be noted that particulate isolation
      methods provide valuable information about particulate size distribution and may
      elucidate the mechanisms of wear associated with polymeric orthopedic implants;
      however, these techniques do not yet provide a direct measure of the amount of
      wear. The aim of this study is to present alternative approaches to wear particle
      isolation for analysis of polymer wear in total joint replacements without
      recourse to ultracentrifugation. Three polymer wear debris isolation techniques
      (the base method, an acid treatment, and an enzymatic digestion technique) are
      compared for effectiveness in simulator studies. A requirement of each technique
      is that the wear particulate must be completely devoid of serum proteins in order
      to effectively image and count these particles. In all methods the isolation is
      performed through filtration and chemical treatment. Subsequently, the isolated
      polymer particles are imaged using scanning electron microscopy and quantified
      with digital image analysis. The results from this study clearly show that
      isolation can be performed without the use of ultracentrifugation and that these
      methods provide a viable option for wear debris analysis.

PMID- 11340594
TI  - Proteomic analysis of human skin fibroblasts grown on titanium: novel approach to
      study molecular biocompatibility.
AB  - Despite the growing use of titanium as an implant material, there is a lack of
      consensus on what constitutes the molecular basis of its biocompatibility. In the
      present study we compared the response of skin fibroblasts to two different
      growth supporting surfaces: commercially pure titanium (cpTi) and tissue culture
      polystyrene (TCPS). Proteins from extracts of whole cells and adsorbed serum were
      separated and identified by 2-dimensional gel electrophoresis. In all, 40
      proteins (46 spots) were identified by matrix-assisted laser
      desorption/ionization and mass spectrometry, database searching, immunoblotting,
      running a standard, or a combination of these techniques. Many of the proteins
      collected from the two surfaces were found to derive from the serum used in the
      culture medium. The surface properties of titanium appeared to promote the
      formation of a more concentrated carpet of serum proteins. Several proteins from
      bovine or human serum, such as albumin, alpha2-HS-glycoprotein, alpha
      fetoprotein, plasminogen, thrombospondin 1, and serotransferrin, along with a few
      unidentified serum components, were found to adsorb onto cpTi in comparatively
      high concentrations. The adsorption of serum proteins did not appear to be
      selective on either substrate. We found that among the major cellular proteins,
      fibronectin and a cytoskeletal protein (non-muscle myosin heavy chain type A)
      were expressed at lower levels by fibroblasts grown on cpTi compared to TCPS. By
      analyzing the changes in the entire proteome of cells in response to different
      growth substrates, we may gain a better understanding of the molecular basis of
      biocompatibility.

PMID- 11340596
TI  - Dissolution of poorly crystalline apatite crystals by osteoclasts determined on
      artificial thin-film apatite.
AB  - Poorly crystalline apatite (PCA) crystals introduced into bone tissue should be
      stable for a definite period before they are dissolved as a result of a host
      response. In this report, the dissolution of PCA crystals by the action of
      osteoclasts was studied on artificial thin films. These consisted of PCA crystals
      having similar crystallographic properties to bone crystals which were developed
      for assaying the osteoclast activity in vitro. The dissolution of minerals by
      osteoclasts decreased along with the decreased amount of labile phosphate and
      hydrogen phosphate domains of apatite crystals, which were caused by the crystal
      maturation temperature. A profound effect on mineral dissolution by pH in the
      culture medium was also shown. Low acidity considerably increased mineral
      dissolution, whereas a slight alkalinity totally blocked mineral dissolution.
      There was little difference in the mineral dissolution behavior of osteoclasts
      near the physiologic pH. In addition, it was determined whether mineral
      dissolution by osteoclasts was dependent on the destruction of the organic
      matrix. Nocodazole was introduced to inhibit the secretion of hydrolytic enzymes,
      and acetazolamide was added to inhibit acid production by the osteoclasts. There
      was no significant change as a result of nocodazole addition on mineral
      dissolution or by the addition of acetazolamide on degradation of collagen. These
      results indicate that small changes in the physicochemical properties of apatite
      crystals can decrease resorption by osteoclasts, which can be highly activated at
      low pH. These results also suggest that mineral dissolution and organic
      degradation by osteoclasts are self-regulating.

PMID- 11340597
TI  - Polyaniline-dacron composite as solid phase in enzyme linked immunosorbent assay
      for Yersinia pestis antibody detection.
AB  - Polyaniline (PANI) was chemically synthesized on a dacron disk surface and an
      antigen (F1 fraction) obtained from Yersinia pestis was covalently fixed onto
      this composite via glutaraldehyde. The enzyme linked immunosorbent assay (ELISA)
      or rapid ELISA procedure detected immunoglobulin G (IgG) anti-F1 fraction in
      human serum employing this derivative. The appropriate conditions for carrying
      out the test were established as an antigen concentration of 2 microg/PANI-dacron
      disk, peroxidase labeled goat anti-human IgG conjugate diluted 4000 times, and a
      serum dilution of 1:100. The PANI-dacron disks showed greater antigen retention
      than conventional poly(vinyl chloride) plates and less antibody unspecific
      adsorption.

PMID- 11340598
TI  - Surface modification of neural recording electrodes with conducting
      polymer/biomolecule blends.
AB  - The interface between micromachined neural microelectrodes and neural tissue
      plays an important role in chronic in vivo recording. Electrochemical
      polymerization was used to optimize the surface of the metal electrode sites.
      Electrically conductive polymers (polypyrrole) combined with biomolecules having
      cell adhesion functionality were deposited with great precision onto
      microelectrode sites of neural probes. The biomolecules used were a silk-like
      polymer having fibronectin fragments (SLPF) and nonapeptide CDPGYIGSR. The
      existence of protein polymers and peptides in the coatings was confirmed by
      reflective microfocusing Fourier transform infrared spectroscopy (FTIR). The
      morphology of the coating was rough and fuzzy, providing a high density of
      bioactive sites for interaction with neural cells. This high interfacial area
      also helped to lower the impedance of the electrode site and, consequently, to
      improve the signal transport. Impedance spectroscopy showed a lowered magnitude
      and phase of impedance around the biologically relevant frequency of 1 kHz.
      Cyclic voltammetry demonstrated the intrinsic redox reaction of the doped
      polypyrrole and the increased charge capacity of the coated electrodes. Rat glial
      cells and human neuroblastoma cells were seeded and cultured on neural probes
      with coated and uncoated electrodes. Glial cells appeared to attach better to
      polypyrrole/SLPF-coated electrodes than to uncoated gold electrodes.
      Neuroblastoma cells grew preferentially on and around the polypyrrole/CDPGYIGSR
      coated electrode sites while the polypyrrole/CH(3)COO(-)-coated sites on the same
      probe did not show a preferential attraction to the cells. These results indicate
      that we can adjust the chemical composition, morphology, electronic transport,
      and bioactivity of polymer coatings on electrode surfaces on a multichannel
      micromachined neural probe by controlling electrochemical deposition conditions.

PMID- 11340600
TI  - Creation of microrough surface on sintered bioactive glass microspheres.
AB  - Bioactive glasses are surface-active, generally silica-based, synthetic materials
      that form a firm chemical bond to bone. The aim of this study was to further
      enhance the bioactivity of glasses by creating a microroughness on their surface.
      Microroughness increases potential surface area for cell attachment and
      biomaterial-cell interactions. Three bioactive glasses of different composition
      were studied. Each material was flame-sprayed into microspheres, and a selected
      fraction of the spheres (250-300 microm) was sintered to form porous bioactive
      glass specimens. To create microrough surfaces, different acid etching techniques
      were tested. Atomic force microscopy (AFM) and back-scattered electron imaging of
      scanning electron microscopy (BEI-SEM) were used to characterize surface
      roughness. The degree of roughness was measured by AFM. A novel chemical-etching
      method, developed through intensive screening of different options, was found
      consistently to create the desired microroughness, with an average roughness
      value (R(a)) of 0.35-0.52 microm and a root mean-square roughness value (R(rms))
      of 0.42-0.64 microm. Microroughening of the glass surface was obtained even in
      the internal parts of the porous glass matrices. Measured by BEI-SEM, the etching
      of a bioactive glass surface did not interfere with the formation of the
      characteristic surface reactions of bioactive glasses. This was confirmed by
      immersing the etched and control glass bodies in a simulated body fluid and
      tris(hydroxymethyl) aminomethane/HCl. The etching process did not significantly
      affect the mechanical strength of the sintered bioactive glass structures. Based
      on these experiments, it seems possible to create a reproducible microroughness
      of appropriate size on the surface of porous bioactive glass. The biologic
      benefits of such a surface treatment need to be validated with in vivo
      experiments.

PMID- 11340599
TI  - Solvent-induced dimensional changes in EDTA-demineralized dentin matrix.
AB  - The purpose of this study was to test the null hypothesis that the re-expansion
      of dried matrix and the shrinkage of moist, demineralized dentin is not
      influenced by polar solvents. Dentin disks were prepared from midcoronal dentin
      of extracted human third molars. After complete demineralization in 0.5M of EDTA
      (pH 7), the specimens were placed in the well of a device that measures changes
      in matrix height in real time. Dry, collapsed matrices were created by blowing
      dry N(2) on the specimens until they shrank to a stable plateau. Polar solvents
      [water, methanol, ethanol, n-propanol, n-butanol, formamide, ethylene glycol,
      hydroxyethyl methacrylate (HEMA), or mixtures of water-HEMA] as model primers
      then were added and the degree of re-expansion measured. These same solvents also
      were applied to moist, expanded matrices and the solvent-induced shrinkages
      measured. Regression analysis was used to test the correlations between matrix
      height and Hansen's dispersive, polar, hydrogen bonding, and total solubility
      parameters (delta(d), delta(p), delta(h), delta(t)). The results indicate that
      water-free polar solvents of low hydrogen bonding (H-bond) ability (e.g., neat
      HEMA) do not re-expand dried matrices and that they shrink moist matrices. When
      HEMA was mixed with progressively higher water concentrations, the model water
      HEMA primers expanded the dried matrix in proportion to their water
      concentrations and they produced less shrinkage of moist matrices. Solvents with
      higher H-bonding capacities (methanol, ethanol, ethylene glycol, formamide, and
      water) re-expanded the dried matrix in proportion to their solubility parameters
      for H-bonding (delta(h)). They also induced small transient shrinkages of moist
      matrices, which slowly re-expanded. The results require rejection of the null
      hypothesis.

PMID- 11340601
TI  - Long-term implantation test and tumorigenicity of polyvinyl alcohol hydrogel
      plates.
AB  - Two types of flat plates made from a polyvinyl alcohol (PVA) hydrogel with a
      water content of 80 and 20 (PVA-H80, PVA-H20), 20 x 10 x 1 mm in size, were
      subcutaneously implanted into each of 50 young, male Wistar rats. As a control, a
      sham operation was done on another set of 50 rats (Sham Op group). The shape and
      transparency of the PVA hydrogel were unchanged for up to 24 months. Tumors arose
      in 14 rats from the PVA-H80 group. In the PVA-H20 group, tumors appeared in 15
      rats. The average tumor latency was 598 +/- 109 days in the PVA-H80 and 637 +/-
      94 days in the PVA-H20. There was no difference in tumor incidence between the
      PVA-H20 and PVA-H80 groups (p < 0.05). In the Sham Op group, no malignant tumors
      appeared. Histopathologically, the tumors induced by hydrogel plates were
      malignant tumors resembling fibrosarcoma or malignant fibrous histiocytoma. This
      indicates that PVA hydrogel implants also induce solid state carcinogenesis at a
      similarly high rate to medical grade hydrophobic material reported in a previous
      study.

PMID- 11340602
TI  - Dental composites reinforced with hydroxyapatite: mechanical behavior and
      absorption/elution characteristics.
AB  - The purpose of this study was to analyze the behavior in water as well as the
      mechanical and surface properties of experimental composites designed for dental
      restoration. Studied materials were composed of a visible-light-cured monomer
      mixture as a matrix (bisphenol-alpha-glycidyl methacrylate with triethyleneglycol
      dimethacrylate or hydroxyethyl methacrylate) and either micrometric or nanometric
      hydroxyapatite (HA) particles as a reinforcing filler. The surface of the filler
      particles was modified by using different coupling agents (citric,
      hydroxysuccinic, acrylic, or methacrylic acid). The hydrolytic stability of the
      evaluated materials was studied through elution-in-water and water-uptake tests.
      Mechanical and surface properties were examined through the results of flexural,
      hardness, and surface roughness tests. Means and standard deviations were
      calculated for each variable. Analysis of variance and multiple comparison tests
      were performed. Materials containing bisphenol-alpha-glycidyl
      methacrylate:triethyleneglycol dimethacrylate and micrometric-HA coated with
      citrate, acrylate, or methacrylate displayed the most favorable results.
      Improvements should be obtained by increasing the total filler amount, and by the
      introduction of nanometric-HA filler into a micrometric-HA reinforced composite
      resin system.

PMID- 11340603
TI  - Proceedings of The Sixth International Conference on the Long-term Complications
      of Treatment of Children and Adolescents for Cancer. Niagara-on-the-Lake,
      Ontario, Canada. June 23-24, 2000.

PMID- 11340604
TI  - Radiation and breast carcinogenesis.
AB  - With the possible exception of radiation-induced leukemia, more is known about
      radiation-induced breast cancer than any other malignancy. Fourteen cohort
      studies have provided quantitative information on the level of risk following a
      wide range of doses in different populations around the world. Comprehensive
      studies have been conducted in Canada, Germany, Japan, Sweden and other Nordic
      countries, the United Kingdom, and the USA [Table I in text]. Key features are
      the linearity in the dose response (i.e., a straight line adequately fits the
      observed data), and the effect modification of age at exposure (i.e., risk is
      inversely related to exposure age and exposures past the menopausal ages appear
      to carry a very low risk); and the minimal effect of fractionating dose on
      subsequent risk. A recent combined analysis of almost 78,000 women and 1,500
      breast cancer cases from eight cohorts confirmed the downturn in risk at the
      highest dose levels (related in part to the killing of cells rather than
      transformation) and that fractionation of dose has little influence on risk, at
      least on an absolute scale. It is not known whether persons predisposed to cancer
      are at enhanced risk of radiation-induced breast cancer from low-dose exposures,
      although this seems unlikely. New data on the effects of high doses following
      childhood exposures will be forthcoming from long-term studies of the survivors
      of childhood cancer.

PMID- 11340605
TI  - The role of hormones in breast carcinogenesis: issues of relevance to female
      childhood cancer survivors.
AB  - Breast cancer is the most common cancer among women in Western industrialized
      countries, and is an important potential second cancer to consider in young women
      who are survivors of childhood or adolescent cancers. This paper reviews the
      relationship between hormones and breast biology, cancer treatment factors that
      may increase or reduce the risk of breast cancer in female survivors of childhood
      cancer, the treatment of ovarian failure in these survivors, and the potential
      for preventive strategies in this population. The expanding numbers of female
      childhood cancer survivors increase the need for health care providers to
      understand the late health effects of treatments on reproductive health and
      breast cancer risk.

PMID- 11340606
TI  - Psychological aspects of cancer screening in high-risk populations.
AB  - BACKGROUND: The focus of this paper is to define who is at high risk for breast
      cancer and the psychological issues in breast cancer screening. Within this
      context, the emphasis is on secondary malignancies after treatment for childhood
      cancers, including age appropriate guidelines for cancer screening. While there
      have been no studies of distress in women at high risk for breast cancer related
      to childhood cancer treatments, we can extrapolate from this study of women at
      high risk for breast cancer because of genetic susceptibility. PROCEDURE: Three
      hundred and ninety one women at increased risk for developing breast cancer from
      rural and urban areas of the United States completed a questionnaire regarding
      genetic testing, psychological distress, and health beliefs. They were compared
      with 382 age-matched controls, from the same geographical areas, with no family
      history of breast cancer in a first degree relative. RESULTS: A multiple
      regression analysis revealed that the best predictors of willingness to undergo
      genetic testing were: greater perception of being a gene mutation carrier, fewer
      negative and more positive aspects to testing, being at higher risk for breast
      cancer, and greater breast cancer anxiety (30% of variance). CONCLUSIONS: Greater
      anxiety increased interest in testing but decreased adherence to screening
      behaviors. Women who have had childhood cancers with chest radiation treatment
      are at higher risk for breast cancer. The information gleaned from this study can
      be adapted to help them learn their real risk for developing breast cancer and to
      understand the importance of screening in the early detection of breast cancer.

PMID- 11340607
TI  - Leukemias related to treatment with DNA topoisomerase II inhibitors.
AB  - The epipodophyllotoxins etoposide and teniposide and other DNA topoisomerase II
      inhibitors including anthracyclines and dactinomycin are highly efficacious
      anticancer drugs. All are associated with a distinct form of leukemia
      characterized by chromosomal translocations as a treatment complication. Most of
      the translocations disrupt a breakpoint cluster region (bcr) of the MLL gene at
      chromosome band 11q23. Other characteristic translocations also may occur. The
      normal function of the nuclear enzyme DNA topoisomerase II is to catalyze changes
      in DNA topology between relaxed and supercoiled states by transiently cleaving
      and re-ligating both strands of the double helix. Anticancer drugs that are DNA
      topoisomerase II inhibitors are cytotoxic because they form complexes with DNA
      and DNA topoisomerase II. The complexes decrease the re-ligation rate, disrupt
      the cleavage-re-ligation equilibrium, and have a net effect of increasing
      cleavage. The increased cleavage damages the DNA and leads to chromosomal
      breakage. Cells with irreparable DNA damage die by apoptosis. The association of
      DNA topoisomerase II inhibitors with leukemia suggests that the drug-induced, DNA
      topoisomerase II-mediated chromosomal breakage may be relevant to translocations
      in addition to this anti-neoplastic, cytotoxic action. Epidemiological studies,
      genomic translocation breakpoint cloning and in vitro DNA topoisomerase II
      cleavage assays together lead to a model for treatment-related leukemia in which
      DNA topoisomerase II causes chromosomal breakage and translocations form when the
      breakage is repaired.

PMID- 11340608
TI  - Therapy-related leukemia associated with alkylating agents.
AB  - The leukemogenic potential of alkylating agents has been known for many years and
      almost all alkylating agents in clinical use have been shown to increase the risk
      of leukemia. With these drugs the risk of leukemia appears to increase with
      increasing patient age, as does the risk of de novo myeloid leukemia in the
      population. Susceptibility to alkylating agent-associated leukemia is influenced
      by the genetic constitution of the patient, and by the nature of the exposure. To
      illustrate the importance of these factors in etiology of leukemia, this paper
      discusses the contribution of disorders such as Fanconi anemia and
      neurofibromatosis to susceptibility to alkylating agent-associated leukemia. This
      paper also discusses the contribution of alkylating agents and other therapeutic
      exposures in the etiology of leukemias occurring after autologous bone marrow
      transplant.

PMID- 11340609
TI  - Genetic predisposition and treatment-related leukemia.
AB  - Treatment-related leukemias are one of the most devastating late complications of
      cancer therapy. Patients with rare cancer predisposition syndromes including
      neurofibromatosis type 1 and inherited p53 mutations are at an increased risk for
      this complication. Other patients may have increased susceptibility because they
      possess common genetic polymorphisms in drug-metabolizing enzymes that result in
      impaired detoxification of chemotherapy or inefficient repair of drug-induced
      genetic damage. We review studies that have identified a potential role for
      polymorphisms in the genes encoding the glutathione-S-transferases (GSTs), NAD(P)
      H: quinone oxidoreductase, myeloperoxidase, N-acetyltransferase (NATs),
      cytochrome P450 (CYP) 1A1 and 3A4, methylenetetrahydrofolate reductase (MTHFR),
      cystathionine-beta-synthase (CBS), and others in the etiology of primary or
      secondary acute leukemias, and therapy-related complications. The identification
      of high risk polymorphisms and use of pharmacogenetically-guided therapies holds
      promise to improve the outcome of cancer therapy and reduce the risk of treatment
      related leukemias.

PMID- 11340610
TI  - Radiation-induced skin cancer in humans.
AB  - The principal epidemiologic studies of ionizing radiation and skin cancer have
      all shown that radiation causes basal cell carcinoma but have not found dose
      related excesses of squamous cell carcinoma or malignant melanoma. The Japanese
      atomic bomb study indicates that doses of radiation under about 1 Gy confer less
      risk per unit dose than higher doses do. All available studies show that skin
      cancer risk is greater from radiation exposure at young ages than at older ages.
      Finding few excess skin cancers among irradiated African-Americans as compared to
      Caucasians with a comparable dose indicates that skin susceptibility to
      ultraviolet exposure modifies the excess risk from ionizing radiation. Available
      evidence indicates that the excess risk of skin cancer lasts for 45 years or more
      following irradiation. Several studies indicate a risk of nonmelanoma skin cancer
      (NMSC) following cancer therapy; however, most of the studies reporting on NMSC
      have not distinguished between patients who received radiotherapy versus
      chemotherapy. Some, but not all, follow-up studies of cancer patients have
      reported excesses of malignant melanoma as second malignant neoplasms. It is not
      clear from the studies how much, if any, of the excess melanoma risk is
      attributable to radiotherapy.

PMID- 11340611
TI  - Genetic determinants of basal cell carcinoma risk.
AB  - Basal cell carcinomas are can be induced by ionizing radiation, in particular in
      patients with the rare autosomal dominant basal cell nevus syndrome (BCNS). These
      patients also are prone to medulloblastomas, and curative ionizing radiation
      therapy for the latter is followed soon by the development of sheets of basal
      cell carcinomas in the overlying skin. Positional cloning of the gene mutant is
      BCNS patients has identified the hedgehog signaling pathway as crucial to the
      development of all basal cell carcinomas and presumably to this susceptibility to
      post-ionizing radiation carcinogenesis. Thus this pathway is a candidate for
      susceptibility to second, post-therapy cancers in the broader population.

PMID- 11340612
TI  - Genetic factors determining cutaneous basal cell carcinoma phenotype.
AB  - BACKGROUND: Basal cell carcinoma (BCC) patients demonstrate considerable
      phenotypic diversity. The basis of this heterogeneity is poorly understood. We
      have shown that presentational phenotypes are associated with BCC numbers. Thus,
      patients with a cluster of new BCC at any presentation comprise a subgroup,
      termed MPP, that is at increased risk of developing numerous lesions. Patients
      with more than one cluster (multiple cluster MPP) are at particular risk.
      PROCEDURE: We determined in a cohort of BCC cases, whether: (i) tumor accrual was
      altered after clustering; and (ii) multiple cluster MPP is associated with
      characteristics linked with sensitivity to UV or, GSTT1, GSTM1, GSTM3, GSTP1,
      MC1R, CYP2D6, TNF-alpha, and VDR genotypes previously associated with BCC
      presentational phenotypes. RESULTS: (i) After clustering BCC accrual increased;
      and (ii) exposure to UV in single and multiple cluster MPP cases were similar. In
      multiple cluster cases, mean age at first presentation with a single tumor
      occurred earlier and, the frequencies of CYP2D6 EM (94.4%) and GSTT1 null (41.2%)
      were significantly greater (P = 0.028 and P = 0.004) than in single cluster cases
      (67.1 and 14.3%). The odds ratios for these associations with the multiple
      cluster MPP were large; 15.5 and 7.39, respectively. CONCLUSIONS: The finding of
      clusters of new, primary BCC is a critical event that is followed by markedly
      increased accrual of further tumors. Clustering occurs at a relatively late age
      and may be associated with a failure in immune surveillance. We propose the MPP
      is not the consequence of excessive UV exposure but reflects the presence of a
      distinct BCC subgroup defined by a combination of risk genes.

PMID- 11340614
TI  - Thyroid cancer after radiotherapy for childhood cancer.
AB  - The thyroid gland in children is among the most sensitive organs to the
      carcinogenic effects of ionizing radiation, and very young children are at
      especially high risk. Risk associated with exposure to external X- or gamma
      radiation increases linearly with increasing dose to the thyroid gland at low-to
      moderate doses, but the dose-response relationship appears to flatten at the very
      high doses characteristic of cancer radiotherapy. Because of the extreme
      sensitivity of the thyroid gland in children, there is a risk of radiation
      induced thyroid cancer even when the thyroid gland is outside of the irradiated
      field. Increased incidence of thyroid cancer has been noted following
      radiotherapy for childhood Hodgkin disease, non-Hodgkin lymphoma, neuroblastoma,
      Wilms tumor, acute lymphocytic leukemia and tumors of the central nervous system.
      Radiation-induced tumors begin to appear 5-10 years after irradiation and excess
      risk persists for decades, perhaps for the remainder of life. The background
      incidence of thyroid cancer is two- to threefold higher among females than males,
      and the absolute increase in risk due to irradiation is higher in females as
      well. Most of the thyroid cancers that occur in association with irradiation are
      of the papillary type, for which the cure rate is high if tumors are detected
      early. This highlights the importance of long-term surveillance of persons
      irradiated during childhood. Important areas for research include the possibility
      that children with certain types of first cancer are especially susceptible, the
      basis of the greater female susceptibility, the joint effects of radiation and
      other factors, and genetic mechanisms in radiation-induced and spontaneously
      occurring thyroid cancer.

PMID- 11340613
TI  - Retinoid chemoprevention in patients at high risk for skin cancer.
AB  - Patients who develop large numbers of skin cancers suffer increased morbidity and
      mortality. A high skin cancer risk can result from inherited disorders such as
      xeroderma pigmentosum (abnormal repair of UV-induced DNA damage) or the nevoid
      basal cell carcinoma syndrome (tumor suppressor gene abnormality). The efficacy
      of systemic retinoid skin cancer chemoprevention was first demonstrated in these
      disorders. Since the mechanism of cancer prevention was not thought to involve
      correction of the underlying defect causing the disorder, individuals at high
      risk for new skin cancers from other causes may also benefit from this approach.
      With the success of organ transplantation, there is a growing population of
      transplant recipients living long, active lives who also have sustained chronic
      UV damage. This population is at high risk for developing aggressive squamous
      cell carcinomas. In this population, extensive skin involvement with human
      papilloma virus induced warts and actinic keratoses results in difficulty with
      diagnosis and monitoring for these dangerous malignancies. Patients who have
      received treatment with agents that cause DNA damage, such as X-radiation, may
      also have a high skin cancer risk. Retinoid chemoprevention may also be of
      benefit in the management of selected patients with these iatrogenic conditions.
      This evolving therapeutic role has heightened the need for the development of new
      retinoids, with more efficacy and less toxicity, for cancer chemoprevention.

PMID- 11340615
TI  - Gene rearrangements in radiation-induced thyroid carcinogenesis.
AB  - BACKGROUND: Radiation is an accepted risk factor for thyroid carcinogenesis in
      children. Recent observations in large cohorts of children and young adults who
      developed papillary thyroid carcinomas (PTC) related to accidental radiation
      exposure after the Chernobyl reactor accident revealed typical genetic
      aberrations shedding light on genetic determinants and mechanisms of radiation
      induced carcinogenesis. PROCEDURE: A molecular genetic analysis was performed on
      191 post-Chernobyl PTC by RT-PCR, multiplex PCR, DNA sequencing, and in some
      cases 5'RACE. Determination of point mutations was by means of PCR and either
      allele-specific oligonucleotide hybridization or SSCP and DNA sequencing.
      RESULTS: In various sporadic thyroid tumor types of adults structural genetic
      aberrations have been found involving mutations of RAS (codon 12, 13, 61), p53
      (exons 5 to 8), Gsalpha (codon 201 and 227), and, at a low prevalence, the
      receptor tyrosine kinases RET or NTRK1. In contrast, in radiation-induced PTC of
      children RET rearrangements are by far the most prevalent genetic aberrations. In
      these RET rearrangements, the transmembrane and extracellular domains of RET are
      lost, and are replaced by parts of other genes at the 5' end. These genes always
      contain coiled-coil domains with dimerization potential and lead to constitutive,
      ligand-independent activation of the ret tyrosine kinase domain at the 3' end of
      the fusion product. The most frequent radiation-induced RET gene fusions involve
      the ELE1 (ARA70) gene, a transcription coactivator of the androgen receptor
      (PTC3), and H4, a gene of unknown function (PTC1). Both rearrangements originate
      from DNA double strand breaks with repair by intrachromosomal balanced
      paracentric inversion and recombination by illegitimate DNA endjoining at small
      stretches of homologous nucleotide sequences and direct or inverted repeats,
      without significant breakpoint clusters in the involved introns. In addition,
      five different RET-fused genes, RIalpha, GOLGA5, HTIF, RFG7 and RFG8, have been
      detected leading to the PTC2, 5, 6, 7 and 8 types of RET rearrangements,
      respectively. Each fusion leads, in principle, to the same effect: The ret
      tyrosine kinase is uncoupled from its stringent physiological regulation by
      replacement of its 5' end and is aberrantly activated by the 5' parts of fused
      genes in thyrocytes that do not normally express ret tyrosine kinase. Ectopic ret
      expression, clonal expansion and early invasion are peculiar to the affected
      cells. The RET-fused gene is obviously decisive for modulating tumor development:
      ELE1/RET rearrangements lead to most rapid tumor progression and are related to
      the solid variant of PTC, in contrast to H4/RET rearrangements connected with
      papillary or follicular variants of PTC. CONCLUSIONS: Typical genetic aberrations
      are produced by radioiodine uptake in the juvenile thyroid gland. They act as
      determinants of phenotype, biology, and clinical course of radiation-induced
      papillary thyroid carcinomas.

PMID- 11340616
TI  - Screening high-risk populations for thyroid cancer.
AB  - BACKGROUND: Children treated with radiotherapy to the neck or exposed to
      environmental radiation are at risk for developing thyroid cancer later in life.
      The best method for screening these high-risk patients is unclear. We
      systematically reviewed evidence on the accuracy of ultrasound and palpation to
      detect thyroid nodules and of fine needle aspiration (FNA), a confirmatory test,
      to diagnose thyroid cancer. PROCEDURE: We searched the MEDLINE database for
      papers published since 1966, using the MeSH term thyroid neoplasms and terms
      related to diagnostic test performance. To supplement our MEDLINE searches, we
      searched reference lists from recent reviews and articles recommended by thyroid
      cancer experts. We recorded the tests used, the gold standard determination of
      disease, the test performance results, and the presence of biases that could
      affect the reported results. We also abstracted the number of patients who
      underwent surgery and the final diagnoses. We created two decision models: one
      for screening 10,000 medically irradiated patients, and one for screening 10,000
      environmentally irradiated patients. RESULTS: Using ultrasound as the gold
      standard determination of the presence of a nodule, the sensitivity of palpation
      for all sized nodules was 10-41 percent, indicating that a high proportion of
      nodules detected by ultrasound are too small to be palpated. Sensitivity of
      palpation increased with nodule size. The specificity of palpation ranged from 95
      to 100%. In studies from referral centers, the reported sensitivity and
      specificity of FNA were 71-95 and 52-99%, respectively. However, most authors
      excluded the proportion of patients (6-33%) who had inadequate or nondiagnostic
      FNA results when calculating sensitivity and specificity, even though 6-100% of
      these patients went on to have a diagnostic lobectomy. When each study was
      reanalyzed so that patients with nondiagnostic FNA results who went directly to
      surgery were reclassified as positive tests, sensitivity increased slightly, but
      specificity dropped by 4-20 percentage points per study. The decision model for
      screening 10,000 medically irradiated patients revealed that if ultrasound were
      used as an initial screen, 2,741 patients would have nodules at least 1 cm in
      size; assuming no patients with smaller nodules had surgery, 1,964 patients would
      have surgery; 275 patients would have a diagnosis of thyroid cancer. Screening
      with ultrasound as an initial test would detect an additional 150 cases of
      thyroid cancer compared to those screened with palpation. However, an additional
      1,689 patients would have surgery for nonmalignant nodules (compared to 480
      patients with nonmalignant nodules screened with palpation). The yield for
      screening 10,000 environmentally irradiated patients was several times smaller
      than for screening 10,000 medically irradiated patients. If 10,000
      environmentally irradiated patients were screened initially with ultrasound,
      approximately 708 patients would have nodules at least 1 cm in size; 89 patients
      would have surgery; and 38 patients would be diagnosed with thyroid cancer.
      CONCLUSIONS: Regardless of type of exposure, testing initially with ultrasound
      detects several times more cases of thyroid cancer than palpation. However, when
      ultrasound is the initial test, many more patients also have surgery for
      nonmalignant nodules. Screening with palpation is not very reassuring,
      particularly to medically irradiated patients with negative tests, since almost
      half (46%) of these patients may have undetected nodules.

PMID- 11340617
TI  - Gene names: the approaching end of a century-long dilemma.

PMID- 11340618
TI  - Comparative insect developmental genetics: phenotypes without mutants.
AB  - The last decade has seen a dramatic increase in interest in the extent to which
      morphological evolution depends on changes in regulatory pathways. Insects
      provide a fertile ground for study because of their diversity and our high level
      of understanding of the genetic regulation of development in Drosophila
      melanogaster. However, comparable genetic approaches are presently possible in
      only a small number of non-Drosophilid insects. In a recent paper, Hughes and
      Kaufman have used a new methodology, RNA interference, in the milkweed bug,
      Oncopeltus fasciatus, to phenocopy the effects of mutations in Hox genes. RNA
      interference involves the injection of double-stranded RNA of the same sequence
      as the relevant mRNA resulting in a depletion of that transcript. Hughes and
      Kaufman focused on the gnathal segments, which elaborate specialized appendages
      important to feeding. Their results indicate that gnathal adaptations in this bug
      are correlated with changes in Hox gene functions and interactions.

PMID- 11340619
TI  - Evolutionary history of vertebrate appendicular muscle.
AB  - The evolutionary history of muscle development in the paired fins of teleost fish
      and the limbs of tetrapod vertebrates is still, to a large extent, uncertain.
      There has been a consensus, however, that in the vertebrate clade the ancestral
      mechanism of fin and limb muscle development involves the extension of epithelial
      tissues from the somite into the fin/limb bud. This mechanism has been documented
      in chondrichthyan, dipnoan, chondrostean and teleost fishes. It has also been
      assumed that in amniotes, in contrast, individual progenitor cells of muscles
      migrate from the somites into the limb buds. Neyt et al. now present the exciting
      finding that in zebrafishes this presumably derived mechanism involving
      individual cell migration, is present. They conclude, based on data on sharks,
      zebrafishes, chickens, quails and mice that the derived mechanism was present in
      the sarcopterygians. This conclusion, however, may be premature in the light of
      further data available in the literature, which show a highly mosaic distribution
      of this character in the vertebrate clade. Furthermore, a developmental mode
      exists that is intermediate between the supposed ancestral and derived modes in
      teleosts, reptiles and possibly amphibians.

PMID- 11340620
TI  - Innexins get into the gap.
AB  - Connexins were first identified in the 1970s as the molecular components of
      vertebrate gap junctions. Since then a large literature has accumulated on the
      cell and molecular biology of this multi-gene family culminating recently in the
      findings that connexin mutations are implicated in a variety of human diseases.
      Over two decades, the terms "connexin" and "gap junction" had become almost
      synonymous. In the last few years a second family of gap-junction genes, the
      innexins, has emerged. These have been shown to form intercellular channels in
      genetically tractable invertebrate organisms such as Drosophila melanogaster and
      Caenorhabditis elegans. The completed genomic sequences for the fly and worm
      allow identification of the full complement of innexin genes in these two
      organisms and provide valuable resources for genetic analyses of gap junction
      function.

PMID- 11340621
TI  - Hypocretin/orexin, sleep and narcolepsy.
AB  - The discovery that hypocretins are involved in narcolepsy, a disorder associated
      with excessive daytime sleepiness, cataplexy and unusually rapid transitions to
      rapid-eye-movement sleep, opens a new field of investigation in the area of sleep
      control physiology. Hypocretin-1 and -2 (also called orexin-A and -B) are newly
      discovered neuropeptides processed from a common precursor, preprohypocretin.
      Hypocretin-containing cells are located exclusively in the lateral hypothalamus,
      with widespread projections to the entire neuroaxis. Two known receptors, Hcrtr1
      and Hcrtr2, have been reported. The functional significance of the hypocretin
      system is rapidly emerging in both animals and humans. Hypocretin abnormalities
      cause narcolepsy in dogs, human and mice. The role of the hypocretin system in
      normal sleep regulation is more uncertain. We believe hypocretin cells drive
      cholinergic and monoaminergic activity across the sleep cycle. Input from the
      suprachiasmatic nucleus to hypocretin-containing neurons may explain the
      occurrence of clock-dependent alertness. Other functions are suggested by
      pharmacological and neurochemical experiments. These include regulation of food
      intake, neuroendocrine function, autonomic nervous system activity and energy
      balance.

PMID- 11340622
TI  - Studies of vitamin A metabolism in mouse model systems.
AB  - Over the past several years, discoveries from mouse genetics have had direct
      impact on our understanding of vitamin A metabolism. Although the metabolism of
      vitamin A in the mouse does have some special features (for example very large
      stores of liver and pulmonary retinyl esters), the ability to construct knockout
      and transgenic mouse models has yielded an impressive amount of information
      directly relevant to understanding the general principles of vitamin A transport,
      storage and degradation. We discuss below the metabolism of vitamin A through a
      number of genetically engineered mouse strains with alterations in genes that
      affect this metabolism. The novelty of this experimental approach is evidenced by
      the fact that the oldest of these strains was first reported only eight years
      ago.1)

PMID- 11340623
TI  - Polyps, peptides and patterning.
AB  - Peptides serve as important signalling molecules in development and
      differentiation in the simple metazoan Hydra. A systematic approach (The Hydra
      Peptide Project) has revealed that Hydra contains several hundreds of peptide
      signalling molecules, some of which are neuropeptides and others emanate from
      epithelial cells. These peptides control biological processes as diverse as
      muscle contraction, neuron differentiation, and the positional value gradient.
      Signal peptides cause changes in cell behaviour by controlling target genes such
      as matrix metalloproteases. The abundance of peptides in Hydra raises the
      question of whether, in early metazoan evolution, cell-cell communication was
      based mainly on these small molecules rather than on the growth-factor-like
      cytokines that control differentiation and development in higher animals.

PMID- 11340624
TI  - Antiviral potential of chemokines.
AB  - In the past few years, a large number of new chemokines (chemotactic cytokines)
      and chemokine receptors have been discovered. The growth in knowledge about these
      molecules has been achieved largely through advances in bioinformatics and the
      expansion of expression sequence tag (EST) databases. It is now clear that
      chemokines are crucial in controlling both the development and functioning of
      leukocytes and that their role is not restricted to cell attraction, as
      originally assumed. In particular, recent findings provide strong support for the
      idea that chemokines and their receptors are especially important in the control
      of viral infection and replication. Thus, specific chemokines are now known to
      enhance the cytotoxic activity of infected cells, thus inhibiting further virus
      replication. In addition, some chemokines orchestrate the recruitment of
      activated leukocytes to foci of infection to aid viral clearance. Viruses, in
      turn, have evolved various defences against chemokines. These range from the
      production of proteins that inhibit biological activity of the host chemokine to
      the hijacking of the chemokine system, whereby certain viruses utilize chemokine
      receptors for their entry. The latter viral defence can itself be blocked by
      chemokines. Altogether, these findings illustrate the central role of chemokines
      in many different phases of the immune response, particularly those aspects
      involving antiviral defence, a variety and versatility that was not fully
      appreciated even a few years ago.

PMID- 11340625
TI  - The Tec family of cytoplasmic tyrosine kinases: mammalian Btk, Bmx, Itk, Tec, Txk
      and homologs in other species.
AB  - Cytoplasmic protein-tyrosine kinases (PTKs) are enzymes involved in transducing a
      vast number of signals in metazoans. The importance of the Tec family of kinases
      was immediately recognized when, in 1993, mutations in the gene encoding Bruton's
      tyrosine kinase (Btk) were reported to cause the human disease X-linked
      agammaglobulinemia (XLA). Since then, additional kinases belonging to this family
      have been isolated, and the availability of full genome sequences allows
      identification of all members in selected species enabling phylogenetic
      considerations. Tec kinases are endowed with Pleckstrin homology (PH) and Tec
      homology (TH) domains and are involved in diverse biological processes related to
      the control of survival and differentiation fate. Membrane translocation
      resulting in the activation of Tec kinases with subsequent Ca2+ release seems to
      be a general feature. However, nuclear translocation may also be of importance.
      The purpose of this essay is to characterize members of the Tec family and
      discuss their involvement in signaling. The three-dimensional structure,
      expression pattern and evolutionary aspects will also be considered.

PMID- 11340626
TI  - Mammalian DNA single-strand break repair: an X-ra(y)ted affair.
AB  - The genetic stability of living cells is continuously threatened by the presence
      of endogenous reactive oxygen species and other genotoxic molecules. Of
      particular threat are the thousands of DNA single-strand breaks that arise in
      each cell, each day, both directly from disintegration of damaged sugars and
      indirectly from the excision repair of damaged bases. If un-repaired, single
      strand breaks can be converted into double-strand breaks during DNA replication,
      potentially resulting in chromosomal rearrangement and genetic deletion.
      Consequently, cells have adopted multiple pathways to ensure the rapid and
      efficient removal of single-strand breaks. A general feature of these pathways
      appears to be the extensive employment of protein-protein interactions to
      stimulate both the individual component steps and the overall repair reaction.
      Our current understanding of DNA single-strand break repair is discussed, and
      testable models for the architectural coordination of this important process are
      presented.

PMID- 11340627
TI  - A plausible function of the prion protein: conjectures and a hypothesis.
AB  - Amyloid beta precursor protein (APP) and prion protein (PrP) are cell membrane
      elements implicated in neurodegenerative diseases. Both proteins undergo
      endoproteolysis. Evidence is adduced from the literature hinting that the process
      in the two proteins could be related, their functions may overlap and their
      distributions coincide. It is proposed that PrP catalyses its own cleavage, the C
      terminal fragment functions as an alpha secretase and the N-terminal segment
      chaperones the active site; the alpha secretase releases anticoagulant and
      neurotrophic ectodomains from APP. The proposals explain some features of
      spongiform encephalopathies.

PMID- 11340628
TI  - Therefore, what are recombination proteins there for?
AB  - The order of discovery can have a profound effect upon the way in which we think
      about the function of a gene. In E. coli, recA is nearly essential for cell
      survival in the presence of DNA damage. However, recA was originally identified,
      as a gene required to obtain recombinant DNA molecules in conjugating bacteria.
      As a result, it has been frequently assumed that recA promotes the survival of
      bacteria containing DNA damage by recombination in which DNA strand exchanges
      occur. We now know that several of the processes that interact with or are
      controlled by recA, such as excision repair and translesion synthesis, operate to
      ensure that DNA replication occurs processively without strand exchanges. Yet the
      view persists in the literature that recA functions primarily to promote
      recombination during DNA repair. With the benefit of hindsight and more than
      three decades of additional research, we reexamine some of the classical
      experiments that established the concept of DNA repair by recombination, and we
      consider the possibilities that recombination is not an efficient mechanism for
      rescuing damaged cells, and that recA may be important for maintaining processive
      replication in a manner that does not generally promote recombination.

PMID- 11340629
TI  - A multicenter clinical trial on the use of alpha1-antichymotrypsin-prostate
      specific antigen in prostate cancer diagnosis.
AB  - BACKGROUND: The aim was to evaluate the clinical performance of alpha(1)
      antichymotrypsin prostate-specific antigen (PSA-ACT) for early diagnosis of
      prostate cancer (PCa) in a multicenter trial. METHODS: Three hundred sixty-seven
      white men with PCa and 290 with benign prostatic hyperplasia (BPH) with tPSA
      concentrations between 2 and 20 microg/L were analyzed. The Elecsys system 2010
      (Roche Diagnostics, Germany) was used for determination of total PSA (tPSA) and
      free PSA (fPSA). The PSA-ACT test was a prototype assay used on the ES system
      (Roche Diagnostics). RESULTS: The median concentrations of tPSA (PCa: 8.43
      microg/L vs. BPH: 6.60 microg/L) and PSA-ACT (8.30 microg/L vs. 6.46 microg/L)
      were significantly different, respectively. The median ratios of fPSA/tPSA (PCa:
      12% vs. BPH: 16%) and PSA-ACT/tPSA (98% vs. 95%) were significantly different.
      Receiver operating characteristics (ROC) analysis for discrimination between PCa
      and BPH (tPSA between 2 and 20 microg/L) was performed with 252 matched pairs and
      showed that the area under the curve (AUC) of the ratio fPSA/tPSA (0.66) was
      significantly different from tPSA (0.50) and PSA-ACT (0.52). PSA-ACT alone or the
      ratio PSA-ACT/tPSA (0.56) were not significantly different from tPSA. For tPSA
      between 4 and 10 microg/L (n = 145 pairs), the AUC of the ratio fPSA/tPSA (0.65)
      was significantly higher than tPSA (0.50) and PSA-ACT (0.54). Significant
      differences between tPSA and PSA-ACT or PSA-ACT/tPSA (0.56) were not found.
      CONCLUSIONS: The determination of PSA-ACT as well as the PSA-ACT/tPSA ratio did
      not improve the diagnostic impact in patients undergoing evaluation for PCa
      compared to fPSA/tPSA ratio.

PMID- 11340630
TI  - Mutation analysis of the p51 gene and correlation between p53, p73, and p51
      expressions in prostatic carcinoma.
AB  - BACKGROUND: p73 and p51 are genes possessing amino-acid similarities to p53. We
      previously found no mutation in p73 in prostatic carcinoma, but did find abnormal
      expression of the gene. Involvement of these genes in prostatic carcinogenesis is
      still poorly understood. METHODS: Mutation analysis of the p51 gene and
      allelotyping of 3q28, on which p51 lies, were performed. Expression of p53, p73,
      and p51 was examined using reverse transcription-polymerase chain reaction, and
      expression levels were compared. RESULTS: No mutation in p51 was found (0/55
      cases). Loss of heterozygosity at 3q28 was detected in 6 of 28 cases (21.8%). By
      expression analysis we found that in p53, 4 of 38 cases (10.5%) showed
      downregulation. No cases showed upregulation of p53. In contrast, p73 and p51
      were downregulated in 42.1 and 39.5% of cases, respectively, and upregulated in
      31.5 and 34.2% of cases, respectively. Expression levels of p51 corresponded with
      those of p73 in 25 of 38 cases (65.8%). CONCLUSIONS: Somatic mutations in p73 and
      p51 are not important in prostatic carcinogenesis. These genes may be associated
      with tumors by expression levels and may have roles in addition to tumor
      suppression.

PMID- 11340631
TI  - Identification of a novel gene on chromosome 13 between BRCA-2 and RB-1.
AB  - METHODS AND RESULTS: By differential display we isolated a new cDNA-fragment,
      named C13, that is downregulated in malignant prostate tissues. Northern
      hybridization revealed the fragment to be part of 3.0 and 4.4 kb mRNAs.
      Fluorescence in situ hybridization, Southern blotting and radiation hybrid
      mapping demonstrated a chromosomal localization of C13 on 13q12-14 closest to the
      SHGC-34125 marker. In the 5% chromosomal environment of C13 we detected changes
      of the allelic status in 13 of 21 prostate cancers. A downregulation was detected
      at the mRNA level in patients with advanced carcinoma. The 3.0 kb full length
      cDNA clone encodes a protein with an open reading frame of 2,202 bp or 733 amino
      acids. The corresponding protein contains a putative nuclear localization signal,
      several glutamine clusters and an alpha-helix-rich domain. By in situ RNA
      hybridization we could demonstrate the mainly epithelial expression of the C13
      mRNA in prostatic tissue. CONCLUSIONS: The localization of C13 between the tumor
      suppressor genes BRCA-2 and RB-1, the detected allelic imbalances, the
      downregulation of its mRNA in some prostatic cancer tissues, the epithelial
      expression and the described protein structure suggest that this gene encodes a
      protein that may have tumor or metastasis suppressing function in prostate
      tissue.

PMID- 11340633
TI  - Pathological features of prostate cancer detected on initial and repeat prostate
      biopsy: results of the prospective European Prostate Cancer Detection study.
AB  - PURPOSE: We evaluated pathological features of prostate cancer detected on repeat
      prostate biopsy in men with a serum total prostate-specific antigen (PSA) level
      between 4 and 10 ng/ml who were diagnosed with benign prostatic tissue after an
      initial biopsy and compared them to those cancers detected on initial prostate
      biopsy. MATERIALS AND METHODS: In this prospective European prostate cancer
      detection study, 1,051 men with a total PSA level between 4 and 10 ng/ml
      underwent transrectal ultrasound (TRUS)-guided sextant biopsy and two additional
      transition zone biopsies. All subjects whose biopsy samples were negative for
      prostate cancer (CaP) underwent a repeat biopsy after 6 weeks. Those with
      clinically localized cancers underwent radical prostatectomy. Pathological and
      clinical features of patients diagnosed with cancer on either initial or repeat
      biopsy and clinically organ confined disease who agreed to undergo radical
      prostatectomy were compared. RESULTS: Initial biopsy was positive (CaP) in 231 of
      1,051 enrolled subjects and negative (benign histology) in 820 subjects. Of these
      820 subjects, CaP was detected in 10% (83/820) upon repeat biopsy. Of cancers
      detected on initial and repeat biopsy, 148/231 (64%) and 56/83 (67.5%) had
      clinically localized disease, respectively, and were offered radical
      prostatectomy. 10/148 (6.7%) and 3/56 (5.3%), respectively, opted for radiation
      therapy and thus, 138/148 (93.3%) and 53/56 (94.7%), respectively, underwent
      radical retropubic prostatectomy. There were statistically significant
      differences with respect to multifocality (P = 0.009) and cancer location (P <
      0.001) with cancers on repeat biopsy showing a lower rate of multifocality and a
      more apico-dorsal location. In contrast, there were no differences with respect
      to stage (P = 0.2), Gleason score (P = 0.36), percentage Gleason grade 4/5 (P =
      0.1), serum PSA (P = 0.62), and patient age (P = 0.517). CONCLUSIONS: At least
      10% of patients with negative prostatic biopsy results will be diagnosed with CaP
      on repeat biopsy. Despite differences in location and multifocality, pathological
      and biochemical features of cancers detected on initial and repeat biopsy are
      similar, suggesting similar biological behavior and thus advocating for a repeat
      prostate biopsy in case of a negative finding on initial biopsy. Cancers missed
      on initial biopsy and subsequently detected on repeat biopsy are located in a
      more apico-dorsal location. Repeat biopsies should thus be directed to this
      rather spared area in order to improve cancer detection rates.

PMID- 11340632
TI  - Increased fatty acid synthase as a therapeutic target in androgen-independent
      prostate cancer progression.
AB  - BACKGROUND: Fatty acid synthase (FAS) performs the anabolic conversion of dietary
      carbohydrate or protein to fat. FAS expression is low in most normal tissues, but
      is elevated in many human cancers, including androgen-sensitive and androgen
      independent prostate cancer. METHODS: Immunohistochemical evaluation of FAS
      expression was performed in human prostate cancer specimens under various states
      of androgen ablation. In vitro and in vivo prostate cancer models were evaluated
      for FAS expression and activity under androgenic and androgen-depleted
      conditions, and were tested for sensitivity to antimetabolite drugs that target
      fatty acid synthesis. RESULTS: While FAS expression in the prostate was androgen
      responsive, it persisted or was reactivated in human prostate carcinoma after
      androgen ablation, and was high in 82% of lethal tumors examined at autopsy.
      Similar patterns of FAS expression and fatty acid synthesis were seen in cell
      culture and xenograft models of human prostate cancer. Pharmacologic inhibition
      of FAS resulted in a dose-dependent reduction of tumor growth in these models,
      including fourfold inhibition of an androgen-independent human prostate cancer
      xenograft with little associated toxicity. CONCLUSIONS: The data suggest that FAS
      expression/FA synthesis provides an important functional aspect of the malignant
      phenotype in prostate cancer, perhaps supporting cell growth or survival. FAS
      expression may be upregulated by alternate signaling pathways important for
      prostate cancer growth under androgen withdrawal. The re-emergence of FAS
      expression and activity during the development of androgen independence
      demonstrate that FAS may serve as a novel target for antimetabolite therapy in
      prostate cancer.

PMID- 11340634
TI  - Transrectal ultrasound for monitoring murine orthotopic prostate tumor.
AB  - BACKGROUND: The mouse orthotopic prostate tumor model has been recognized as an
      ideal preclinical animal model simulating the anatomical and biological milieu of
      the prostate. In comparison with the subcutaneous tumor model, the only
      disadvantage of this model is the difficulty of chronological tumor growth
      monitoring. We have applied recent endoluminal ultrasound technology, transrectal
      ultrasonography (TRUS), to the monitoring of mouse orthotopic prostate tumors.
      METHODS: A 6 Fr. 20 MHz catheter-based radial scan probe was used and TRUS was
      performed without any prior preparation including anesthesia. Orthotopic tumors
      were initiated by inoculation of 5000 RM-9 cells into the dorsal prostate of 12
      week-old C57BL/6 male mice. The tumor growth was monitored by TRUS from day 3 to
      day 21. In addition, TRUS was performed to detect tumor growth suppression after
      intraperitoneal administration of cis-diamminedichloroplatinum (CDDP). RESULTS:
      By ultrasound, tumors became detectable 7 days after tumor cell inoculation. TRUS
      images were clear and parallel to actual tumor growth. The tumor volume (X)
      calculated by TRUS correlated significantly with the actual tumor weight (Y)
      measured at autopsy; Y = 101.653 + 1.174X (R = 0.930, P < 0.001). Similarly,
      tumor growth suppression induced by CDDP was clearly detected by TRUS with
      reasonable accuracy. CONCLUSIONS: A high resolution TRUS allows simple and
      reliable monitoring of in situ tumor growth and growth suppression, making the
      mouse orthotopic prostate tumor model more efficient.

PMID- 11340635
TI  - PRAC: A novel small nuclear protein that is specifically expressed in human
      prostate and colon.
AB  - BACKGROUND: The database of human Expressed Sequence Tags (dbEST) provides a
      potential source for identification of tissue-specific genes. This database
      contains sequences that originate from cDNA libraries from particular tumors,
      organs or cell types. In this report, we have used the EST database to identify
      PRAC, a novel gene specifically expressed in human Prostate, prostate cancer,
      Rectum And distal Colon. METHODS: Using a computer based analysis, a cluster of
      sequence homologous ESTs was identified which contained ESTs derived only from
      human prostate cDNA libraries. The tissue specificity was examined by multiple
      tissue RNA dot blots and RT-PCR. The PRAC transcript and protein was identified
      using Northern blot analysis, RACE-PCR, primer extension, and western blot.
      RESULTS: PRAC encode a 382 nucleotide RNA found in prostate, rectum, distal
      colon, and in three prostate cancer cell lines; LNCaP, PC-3 and DU145. This
      transcript encodes a 6 kDa nuclear protein. The PRAC gene is located on
      chromosome 17 at position 17q21, about 4 kbp downstream from the homeodomain Hoxb
      13 gene. CONCLUSIONS: Our data proves that the EST database can be a useful tool
      for discovery of prostate-specific genes. The nuclear localization,
      identification of potential phosphorylation sites, and possible cotranscription
      with the Hoxb-13 gene suggest that PRAC may have a regulatory role in the
      nucleus.

PMID- 11340636
TI  - Identification of differentially expressed genes in organ-confined prostate
      cancer by gene expression array.
AB  - BACKGROUND: To understand the molecular mechanisms underlying prostate cancer, we
      have utilized the gene expression array to search for genes whose expression is
      altered in this disease. METHODS: RNA quality from manual microdissected tissue
      was compared with that from microselected tissue by electrophoresis. For array
      analysis, malignant and normal prostate epithelium was enriched using
      microselection technique from prostate cancer and the peripheral zone of a normal
      prostate. Identical array membrane was hybridized to labeled cancer and normal
      cDNA, respectively. The differentially expressed gene was further evaluated by RT
      PCR. RESULTS: Microdissection, but not microselection, causes visible degradation
      to RNA. Of the 588 genes on the membrane, 87 genes yielded significant signals.
      Based on a three fold difference relative to normal prostate tissue, 1 gene was
      overexpressed and 12 genes underexpressed in prostate cancer. Of them, five
      showed statistically significant reduction in mRNA levels in six prostate cancer
      specimens compared with seven normal prostate specimens. These five genes are
      glutathione S-transferase M1 (GSTM1), monocyte chemotactic protein-1 (MCP-1),
      tumor necrosis factor-alpha receptor-1 (TNFR-1), transforming growth factor beta3
      (TGF-beta3), and inhibitor of DNA binding-1 (ID-1). CONCLUSIONS: GST-based
      metabolism, cytokine MCP-1 and TNFR-1, and TGF-beta3 signaling pathways, and some
      helix-loop-helix nuclear proteins could be potentially important in organ
      confined prostate cancer and deserve further investigation.

PMID- 11340637
TI  - Temperature and time interval for culture of postmortem neurons from adult rat
      cortex.
AB  - For a model of neurological disease and ischemia, we extended recent work to
      culture adult postmortem rat brain neurons. Frontal cortex sections were removed
      from adult rats immediately following sacrifice and at different postmortem
      intervals and with the brain at either 22 degrees C or 4 degrees C. Brain could
      be stored four times longer at 4 degrees C between sacrifice and neuronal
      disaggregation to achieve the same 20% recovery of live cells from those plated
      compared to 22 degrees C. Each milligram of rat frontal cortex was estimated by
      the optical disector method to contain 160,000 neurons. When cells were isolated
      as rapidly as possible, 9% of the neurons originally present in the brain were
      viable. Various postmortem intervals from 2 to 24 hr resulted in a reduction from
      6% to 3% of the cells originally present. After 5 days in culture, viable neurons
      were 23-42% of those isolated. Neuron-like cells that survived represented 40-75%
      of the viable cells, or 0.5-2.75% of those originally estimated to be present in
      the brain. Electrophysiology experiments show that cells isolated 0 and 24 hr
      postmortem had neuronal electrical properties, including an average resting
      membrane potential of -48 mV, voltage-sensitive currents, and action potentials.
      Neuron-like cells were immunoreactive for neuron-specific enolase, neurofilament
      200, glutamate, MAP2, and tau after 2 weeks in culture. These experiments show
      that neuron-like cells can be reliably cultured from adult rat cortex up to 6 hr
      postmortem when stored at 22 degrees C and up to 24 hr postmortem when stored at
      4 degrees C. These findings should encourage donation of human postmortem brain
      neurons for studies on ischemia, adult pharmacology, and neurological disease.

PMID- 11340638
TI  - In vitro regulated expression of tyrosine hydroxylase in ventral midbrain neurons
      from Nurr1-null mouse pups.
AB  - The transcription factor Nurr1, an orphan member of the steroid-thyroid hormone
      nuclear receptor superfamily, is essential for the proper terminal
      differentiation of ventral midbrain dopaminergic neurons. Disruption of the Nurr1
      gene in mice by homologous recombination abolishes synthesis of dopamine (DA) and
      expression of DA biosynthetic enzymes, including tyrosine hydroxylase (TH), in
      the ventral midbrain without affecting the synthesis of DA in other areas of the
      brain. At birth, however, dopaminergic neuron precursors in Nurr1 null (-/-) pups
      remain as shown by continued expression of residual, untranslated Nurr1 mRNA not
      altered by homologous recombination. Since Nurr1 disruption is lethal shortly
      after birth, to further investigate the developmental properties of these
      neurons, dissociated ventral midbrain neurons from newborn pups were grown for 5
      days on an astrocyte feeder layer, subjected to various treatments and then
      evaluated for expression of TH by fluorescent immunocytochemistry. Initially, a
      small percentage of neurons (0.26% +/- 0.07%) from the ventral midbrain of Nurr1 
      /- pups were TH-immunoreactive (TH-IR). No change in TH expression was observed
      in the presence of glial cell line-derived neurotrophic factor (GDNF), brain
      derived neurotrophic factor (BDNF), or DA alone or in combination. Treatment with
      forskolin (Fsk), however, significantly increased the percentage of TH-IR neurons
      (1.36% +/- 0.15%). Combination of Fsk, BNDF, and DA further increased the
      percentage of TH-IR neurons (2.58% +/- 0.50%). Therefore, these data suggest that
      dopaminergic neuron precursors, which develop in vivo without Nurr1, remain in an
      undifferentiated condition that is permissive to the induction of TH in vitro. J.
      Neurosci. Res. 64:322-330, 2001. Published 2001 Wiley-Liss, Inc.

PMID- 11340639
TI  - Antibody to the extracellular domain of the low affinity NGF receptor stimulates
      p75(NGFR)-mediated apoptosis in cultured sympathetic neurons.
AB  - Recent evidence has established a role for p75(NGFR) in developmentally regulated
      neuronal cell death. Although cell death due to NGF withdrawal is a well
      described, apoptosis in sympathetic neurons through stimulation of p75(NGFR) has
      not been clearly demonstrated. We have found that an antibody directed against
      the extracellular domain of murine p75(NGFR) profoundly effects the survival of
      short-term cultures of sympathetic neurons. Rat superior cervical ganglion
      neurons grown in the presence of NGF and treated with the bioactive antibody
      (9651) display a dose-dependent increase in cell death. This effect was
      independent of NGF concentration and partially reversed by either depolarizing
      stimuli or forskolin. The response to 9651 seems to act directly through a
      p75(NGFR)-mediated pathway and not by disturbing p75(NGFR)/TrkA interactions.
      Moreover, the kinetics of antibody stimulated cell death was more rapid than the
      cell death resulting from removal of NGF and treatment with CNTF failed to
      promote neuronal survival in the presence of 9651. Initiation of cell death is
      often associated with decreased NFkappaB activity, whereas survival or rescue
      correlates with increased NFkappaB. Increases in NFkappaB, however, have been
      observed in neurons in several diseases and late in apoptosis in differentiated
      PC12 cells. Time course studies revealed a rapid decrease in NFkappaB activity
      and a slight, but persistent increase in binding that correlated with decline in
      cell numbers 3 hr after treatment. These results suggest the cell death program
      is initiated shortly after antibody activation of p75(NGFR) and a subpopulation
      of cells may remain susceptible to rescue.

PMID- 11340640
TI  - Endogenous IGF1 enhances cell survival in the postnatal dentate gyrus.
AB  - The dentate gyrus is selectively reduced in size in the insulin-like growth
      factor 1 (IGF1) null mouse brain. The purpose of this study was to determine
      whether this defect is due to reduced granule cell numbers, and if so, to
      determine whether altered cell proliferation, survival, or both contribute to
      attenuation of dentate gyrus size. At postnatal day 10 (P10), granule cell
      numbers were not significantly different in IGF1 null and littermate wildtype
      (WT) dentate gyri. The subgranular zone cell population, however, was relatively
      increased, and the granule cell layer population relatively decreased in the IGF1
      null dentate gyrus. By P50, total dentate cell numbers were decreased by 20% (P =
      0.01) in the IGF1 null mouse, although IGF1 null subgranular zone progenitor
      cells remained relatively increased compared with WT (38%, P < 0.05). IGF1 null
      dentate cell proliferation, assessed by thymidine analogue incorporation, was
      actually increased at P10 (33%, P < 0.05) and P50 (167%, P = 0.001). Dentate
      granule cell death, assessed by the appearance of pycnotic cells and DNA
      fragmentation, was also significantly increased in the IGF1 null dentate (61%, P
      < 0.05 and 101%, P = 0.03). These data suggest that endogenous IGF1 serves an
      important role in dentate granule cell survival during the course of postnatal
      brain development. In addition, this work suggests the potential of a
      compensatory mechanism promoting increased dentate cell proliferation in the face
      of impaired cell survival during postnatal neurogenesis. J. Neurosci. Res. 64:341
      347, 2001. Published 2001 Wiley-Liss, Inc.

PMID- 11340641
TI  - Purkinje cell degeneration in mice lacking the xeroderma pigmentosum group G
      gene.
AB  - Laboratory mice carrying the nonfunctional xeroderma pigmentosum group G gene
      (the mouse counterpart of the human XPG gene) alleles have been generated by
      using gene-targeting and embryonic stem cell technology. Homozygote animals of
      this autosomal recessive disease exhibited signs and symptoms, such as postnatal
      growth retardation, reduced levels of activity, progressive ataxia and premature
      death, similar to the clinical manifestations of Cockayne syndrome (CS).
      Histological analysis of the cerebellum revealed multiple pyknotic cells in the
      Purkinje cell layer of the xpg homozygotes, which had atrophic cell bodies and
      shrunken nuclei. Further examination by an immunohistochemistry for calbindin-D
      28k (CaBP) showed that a large number of immunoreactive Purkinje cells were
      atrophic and their dendritic trees were smaller and shorter than in wild-type
      littermates. These results indicated a marked degeneration of Purkinje cells in
      the xpg mutant cerebellum. Study by in situ detection of DNA fragmentation in the
      cerebellar cortex demonstrated that some deoxynucleotidyl transferase (TdT)
      mediated dUTP-biotin in situ nick labeling (TUNEL)-positive cells appeared in the
      granule layer of the mutant mice, but few cell deaths were confirmed in the
      Purkinje layer. These results suggested Purkinje cell degeneration in the mutant
      cerebellum was underway, in which much Purkinje cell death had not appeared, and
      the appearance of some abnormal cerebellar symptoms in the xpg-deficient mice was
      not only due to a marked Purkinje cell degeneration, but also to damage of other
      cells.

PMID- 11340642
TI  - BDNF dependence in neuroblastoma.
AB  - Neuroblastomas are heterogeneous tumors arising from sympathetic precursors in
      the neural crest. Growth factor stimulation of neuroblastomas promote diverse
      biological responses (mitogenesis, differentiation, cell death) depending on the
      particular tumor studied. Here we show that brief treatment with retinoic acid
      (RA) rendered the human neuroblastoma lines SY5Y, NGP, SMS-KCNR, and SK-N-SH
      dependent on brain-derived neurotrophic factor (BDNF) for survival. The BDNF- and
      trkB-expressing line SMS-KCN was dependent on an autocrine BDNF/trkB survival
      without exposure to RA. We conclude that the BDNF/trkB pathway plays an important
      role in neuroblastoma survival and speculate on a possible role in tumor
      pathogenesis.

PMID- 11340643
TI  - Neurofilaments of Klotho, the mutant mouse prematurely displaying symptoms
      resembling human aging.
AB  - We reported previously that neurofilaments (NFs) of aged rats were highly packed
      in the axon and contained a smaller amount of NF-M as compared with those of
      young rats (Uchida et al. [1999] J. Neurosci. Res. 58:337-348). We studied NFs of
      the mutant mouse, named Klotho, which displays prematurely symptoms resembling
      human aging. The transport of axonal cytoskeletal proteins, including NFs,
      tubulin and actin, was decreased at the leading portion of the peak of
      transported proteins in Klotho during the process of premature aging. The nearest
      neighbor inter-NF distance in Klotho axons (35-39 nm) was shorter than that of
      the wild-type mouse (48-49 nm), indicating the packing of NFs in Klotho. The
      ratio of NF-M to NF-L was slightly decreased in cytoskeletons from the spinal
      cords of Klotho. These changes are similar, though not identical, to those
      observed in aged rats, and are the first evidence of age-related changes in the
      neurons of Klotho.

PMID- 11340644
TI  - Caspase-3 activation in oligodendrocytes from the myelin-deficient rat.
AB  - The myelin-deficient (MD) rat has a point mutation in its proteolipid protein
      (PLP) gene that causes severe dysmyelination and oligodendrocyte cell death.
      Using an in vitro model, we have shown that MD oligodendrocytes initially
      differentiate similarly to wild-type cells, expressing galactocerebroside, 2',3'
      cyclic nucleotide 3'-phosphodiesterase, and myelin basic protein. However, at the
      time when PLP expression would normally begin, the MD oligodendrocytes die via an
      apoptotic pathway involving caspase activation. The active form of caspase-3 was
      detected, along with the cleavage products of poly-(ADP-ribose) polymerase (PARP)
      and spectrin, major targets of caspase-mediated proteolysis. A specific inhibitor
      of casapse-3, Ac-DEVD-CMK, reduced apoptosis in MD oligodendrocytes, but the
      rescued cells did not mature fully or express myelin-oligodendrocyte
      glycoprotein. These results suggest that mutant PLP affects not only cell death
      but also oligodendrocyte differentiation.

PMID- 11340645
TI  - Structural dynamics of oligodendrocyte lysis by perforin in culture: relevance to
      multiple sclerosis.
AB  - The mechanism by which oligodendrocytes are depleted from active lesions in
      multiple sclerosis (MS) is not clear but many reports implicate a cytolytic
      process. The most applied animal model for MS, chronic relapsing experimental
      autoimmune encephalomyelitis (EAE), has been established in inbred strains of
      mice, especially SJL and PL. Studies on oligodendrocytes from these strains in
      vitro have been hampered to date by an inability to grow these cells from mouse
      CNS tissue. We report here a successful method to culture SJL mouse
      oligodendrocytes and have analyzed lysis of these cells in vitro mediated by the
      pore-forming protein, perforin, a candidate effector molecule in inflammatory
      demyelination. Cultures were exposed to murine perforin, 36-72 hemolytic U, for
      up to 2.5 hr and examined using the oligodendrocyte phenotypic markers O4,
      galactocerebroside and myelin basic protein (MBP), in addition to a membrane dye
      (DiI) and a marker of necrosis, propidium iodide, (PI). Cultures were imaged
      chronologically by phase contrast, immunofluorescence, digital, light and
      electron microscopy. Findings showed that the majority of oligodendrocytes were
      killed within 60-90 min via pore expansion and ultimately, membrane disruption.
      The structural features of the cellular damage comprised swelling of the cell
      body, fenestration and fragmentation of membranes and processes, cytoplasmic
      vacuolation and breakdown of the nuclear envelope. Astrocytes in the same system
      were relatively resistant to cell lysis. The above patterns of oligodendrocyte
      damage in SJL oligodendrocytes were reminiscent of patterns in the MS lesion,
      leaving us to conclude that perforin may play an important role in the human
      disease.

PMID- 11340646
TI  - L-Serine regulates the activities of microglial cells that express very low level
      of 3-phosphoglycerate dehydrogenase, an enzyme for L-Serine biosynthesis.
AB  - Microglia are well known to become activated during various kinds of
      neuropathological events. The factors that are responsible for the activation,
      however, are not fully determined. In the present study, L-Ser was shown to
      enhance production of nitric oxide (NO), interleukin-6 (IL-6) and tumor necrosis
      factor alpha (TNF alpha) by lipopolysaccharide (LPS)-stimulated cultured rat
      microglial cells. L-Ser, however, did not enhance the expression of mRNAs
      encoding inducible NO synthase, IL-6 and TNF alpha. On the other hand, astrocytes
      did not depend on L-Ser for release of IL-6 and TNF alpha. The expression of an
      enzyme 3-phosphoglycerate dehydrogenase (3PGDH), which is essential for L-Ser
      biosynthesis from a glycolytic intermediate 3-phosphoglycerate, was investigated.
      As revealed by Western blotting and immunocytochemical staining, 3PGDH-protein
      expression in vitro was the highest in astrocytes, intermediate in neurons and
      the lowest in microglial cells. Semiquantitative RT-PCR showed that microglial
      cells expressed 3PGDH-mRNA at a lower level than astrocytes. In frozen sections
      from rat forebrain, only astrocytes were immunoreactive for 3PGDH. The present
      study suggested that L-Ser is able to modulate microglial function mainly at the
      translation level because microglial cells cannot synthesize sufficient amount of
      L-Ser due to the scarce expression of 3PGDH.

PMID- 11340647
TI  - Inhibitory effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on cAMP-induced
      differentiation of rat C6 glial cell line.
AB  - Dioxin is suspected to cause adverse effects on the development of the central
      nervous system (CNS). To investigate the neurotoxic effects of dioxin on the
      differentiation of astrocytes, rat C6 glial cell line was used as a model,
      because these cells are induced to express astrocyte markers and to change the
      cell morphology toward an astrocytic phenotype by increasing intracellular cAMP
      levels. When C6 cells were simultaneously exposed to 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD) and N(6),O(2')-dibutylyl cAMP (dbcAMP), the expression of
      cytochrome P-450 1A1 (CYP1A1) was dramatically increased, and the expression of
      aryl hydrocarbon receptor (AhR) was moderately decreased in a dose-dependent
      manner. In addition, extension of astrocytic processes was inhibited by 1 nM TCDD
      that did not reduce cell viability. TCDD also inhibited the induction of glial
      fibrillary acidic protein (GFAP) expression in a dose-dependent manner, until the
      end of a 72-hr exposure period. This inhibition was restored by the addition of
      an antagonist of AhR, alpha-naphthoflavone. These results indicate that TCDD
      inhibits astrocytic differentiation of C6 cells, which may be mediated by an AhR
      dependent pathway.

PMID- 11340648
TI  - Inhibitory effect of neuropeptide Y on morphine withdrawal is accompanied by
      reduced c-fos expression in specific brain regions.
AB  - Neuropeptide Y (NPY) was previously shown in our laboratory to attenuate
      behavioral signs of morphine withdrawal. To further characterize the anti
      withdrawal effect of NPY, the present study attempted to identify specific brain
      regions where NPY inhibits neuronal activity during withdrawal. Morphine
      dependence was induced in male Wistar rats by two daily subcutaneous injections
      of morphine at increasing doses, and the withdrawal syndrome was precipitated
      acutely by intraperitoneal administration of naloxone. Rats were pre-treated with
      an intracerebroventricular (icv) injection of NPY (12 nmol) or vehicle 30 min
      before the naloxone challenge. Withdrawal behavior was quantified using a point
      scoring technique based on motor- and non-motor-related signs. Brain areas
      involved in the attenuation of morphine withdrawal were delineated by radioactive
      in situ hybridization for the immediate early gene c-fos, which is a marker for
      neuronal activity. The present study confirmed the inhibitory effect of NPY on
      withdrawal behavior. Inhibition of behavioral signs of naloxone-precipitated
      morphine withdrawal was accompanied by significantly reduced c-fos expression in
      the locus coeruleus, lateral septal nucleus, ventral part of the periaqueductal
      grey, cingulate and frontal cortices, and septohippocampal nucleus. Our data
      suggest that neo- and allo-cortical areas as well as specific brainstem nuclei
      are involved in the anti-withdrawal effects of NPY.

PMID- 11340649
TI  - Strategies for neuroprotection against L-trans-2,4-pyrrolidine dicarboxylate
      induced neuronal damage during energy impairment in vitro.
AB  - Increased levels of extracellular excitatory amino acids and failure of energy
      metabolism are two conditions associated with brain ischemia. In the present
      study we have combined the simultaneous inhibition of glutamate uptake and
      mitochondrial electron transport chain to simulate neuronal damage associated
      with brain ischemia. Results show that cerebellar granule neurons are not
      vulnerable to transient glutamate uptake inhibition by L-trans-pyrrolidine-2,4
      dicarboxylate (PDC) despite the increase in the extracellular concentration of
      glutamate, unless they are simultaneously exposed to the mitochondrial toxins 3
      nitropropionic acid (3-NP) or sodium azide. Cell damage was assessed by light
      microscopy observation, by reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT), and by the fluorescent markers for live and
      dead cells, calcein and ethidium homodimer, respectively. The protective effect
      of alternative energy substrates, such as pyruvate, acetoacetate, and beta
      hydroxybutyrate against PDC-induced neuronal death during 3-NP exposure was
      studied and compared to the effects of the antioxidant vitamin E, the spin
      trapper alpha-phenyl-N-tert-butylnitrone (PBN), voltage-dependent calcium channel
      antagonists, and glutamate receptor antagonists. Results show that neuronal
      damage can be efficiently prevented in the presence of pyruvate and the N-methyl
      D-aspartate (NMDA) receptor antagonist MK-801, whereas the non-NMDA receptor
      antagonist NBQX, acetoacetate, vitamin E, and PBN showed partial protection. In
      contrast, beta-hydroxybutyrate and voltage-dependent calcium channels blockers
      did not show any protective effect at the concentrations tested.

PMID- 11340650
TI  - Cannabinoid receptor agonist-stimulated [35S]guanosine triphosphate gammaS
      binding in the brain of C57BL/6 and DBA/2 mice.
AB  - The two inbred strains of mice C57BL/6 (alcohol-preferring) and DBA/2 (alcohol
      avoiding) mice have been shown to differ significantly in their preference for
      alcohol (EtOH). We have previously demonstrated the differences in the density
      and the affinity of cannabinoid (CB1) receptors in the brains of the two inbred
      C57BL/6 and DBA/2 mouse strains. In the present study, we investigated the CB1
      receptor agonist-stimulated guanosine-5'-O-(3-[(35)S]thio)-triphosphate
      ([(35)S]GTPgammaS) binding in plasma membranes (PM) from C57BL/6 and DBA/2 mice.
      The results indicate that the net CP55,940-stimulated [(35)S]GTPgammaS binding
      was increased with increasing concentrations of CB1 receptor agonists and GDP.
      The net CB1 receptor agonist (WIN55,212-2 or HU-210 or CP55,940)-stimulated
      [(35)S]GTPgammaS binding was reduced significantly (-10% to -12%, P < 0.05) in PM
      from DBA/2 mice; no significant differences were observed in basal
      [(35)S]GTPgammaS binding among these strains. Nonlinear regression analysis of
      net CP55,940-stimulated [(35)S]GTPgammaS binding showed that the B(max) of
      cannabinoid agonist-stimulated binding was significantly reduced (-24%) in DBA/2
      mice (B(max) = 12.43 +/- 0.64 for C57BL/6 and 9.46 +/- 0.98 pmol/mg protein for
      DBA/2; P < 0.05) without any significant changes in the G protein affinity. The
      pharmacological specificity of CP55,940-stimulated [(35)S]GTPgammaS binding was
      examined with CB1 receptor antagonist SR141716A, and these studies indicated that
      CP55,940-stimulated [(35)S]GTPgammaS binding was blocked by SR141716A, with a
      decrease in the IC(50) values in the PM from the DBA/2 mouse strain. These
      results suggest that a signal transduction pathway(s) downstream from the CB1
      receptor system may play an important role in controlling the voluntary EtOH
      consumption by these strains of mice.

PMID- 11340651
TI  - Molecular mechanisms of microheterogeneity-induced defect formation in ferritin
      crystallization.
AB  - We apply in situ atomic force microscopy to the crystallization of ferritins from
      solutions containing approximately 5% (w/w) of their inherent molecular dimers.
      Molecular resolution imaging shows that the dimers consist of two bound monomers.
      The constituent monomers are likely partially denatured, resulting in increased
      hydrophobicity of the dimer surface. Correspondingly, the dimers strongly adsorb
      on the crystal surface. The adsorbed dimers hinder step growth and on
      incorporation by the crystal initiate stacks of up to 10 triple and single
      vacancies in the subsequent crystal layers. The molecules around the vacancies
      are shifted by approximately 0.1 molecular dimensions from their crystallographic
      positions. The shifts strain the lattice and, as a consequence, at crystal sizes
      > 200 microm, the accumulated strain is resolved by a plastic deformation
      whereupon the crystal breaks into mosaic blocks 20-50 microm in size. The
      critical size for the onset of mosaicity is similar for ferritin and apoferritin
      and close to the value for a third protein, lysozyme; it also agrees with
      theoretical predictions. Trapped microcrystals in ferritin and apoferritin induce
      strain with a characteristic length scale equal to that of a single point defect,
      and, as a consequence, trapping does not contribute to the mosaicity. The
      sequence of undesired phenomena that include heterogeneity generation,
      adsorption, incorporation, and the resulting lattice strain and mosaicity in this
      and other proteins systems, could be avoided by improved methods to separate
      similar proteins species (microheterogeneity) or by increasing the biochemical
      stability of the macromolecules against oligomerization.

PMID- 11340652
TI  - Charge centers and formation of the protein folding core.
AB  - Electrostatic interactions are important for protein folding. At low resolution,
      the electrostatic field of the whole molecule can be described in terms of charge
      center(s). To study electrostatic effects, the centers of positive and negative
      charge were calculated for 20 small proteins of known structure, for which
      hydrogen exchange cores had been determined experimentally. Two observations seem
      to be important. First, in all 20 proteins studied 30-100% of the residues
      forming hydrogen exchange core(s) were clustered around the charge centers.
      Moreover, in each protein more than half of the core sequences are located near
      the centers of charge. Second, the general architecture of all-alpha proteins
      from the set seems to be stabilized by interactions of residues surrounding the
      charge centers. In most of the alpha-beta proteins, either or both of the centers
      are located near a pair of consecutive strands, and this is even more
      characteristic for alpha/Beta and all-beta structures. Consecutive strands are
      very probable sites of early folding events. These two points lead to the
      conclusion that charge centers, defined solely from the structure of the folded
      protein may indicate the location of a protein's hydrogen exchange/folding core.
      In addition, almost all the proteins contain well-conserved continuous
      hydrophobic sequences of three or more residues located in the vicinity of the
      charge centers. These hydrophobic sequences may be primary nucleation sites for
      protein folding. The results suggest the following scheme for the order of events
      in folding: local hydrophobic nucleation, electrostatic collapse of the core,
      global hydrophobic collapse, and slow annealing to the native state. This
      analysis emphasizes the importance of treating electrostatics during protein
      folding simulations.

PMID- 11340653
TI  - Molecular dynamics studies on HIV-1 protease drug resistance and folding
      pathways.
AB  - Drug resistance to HIV-1 protease involves the accumulation of multiple mutations
      in the protein. We investigate the role of these mutations by using molecular
      dynamics simulations that exploit the influence of the native-state topology in
      the folding process. Our calculations show that sites contributing to phenotypic
      resistance of FDA-approved drugs are among the most sensitive positions for the
      stability of partially folded states and should play a relevant role in the
      folding process. Furthermore, associations between amino acid sites mutating
      under drug treatment are shown to be statistically correlated. The striking
      correlation between clinical data and our calculations suggest a novel approach
      to the design of drugs tailored to bind regions crucial not only for protein
      function, but for folding as well.

PMID- 11340654
TI  - Significance of aromatic-backbone amide interactions in protein structure.
AB  - Weakly polar interactions between aromatic rings of amino acids and hydrogens of
      backbone amides (Ar-HN) have been shown to support local structures in proteins.
      Their role in secondary structures, however, has not been elucidated. To
      investigate the relationship between Ar-HN interaction and the stability of local
      and secondary structures of polypeptides and to improve the prediction of this
      interaction based on amino acid sequence, the structures of 560 nonhomologous
      proteins, from the Protein Data Bank, were searched for Ar-HN interactions
      between the aromatic ring of each Phe, Tyr, and Trp residue at position i and the
      backbone amide group of any residue, except Pro, at the positions i, i - 1, i -
      2, i - 3, i + 1, i + 2, and i + 3. Ar-HN interactions were identified by
      calculating the chemical shift of the amide hydrogen caused by the proximal
      aromatic ring. Ar(i)-HN(i + 1, i + 2 and i + 3) interactions were more common
      (7.10%, 2.08%, and 0.54%, respectively) than were Ar(i)-HN(i - 1, i - 2, and i -
      3) interactions (0.66%, <0.1%, and 0.18%, respectively). The value of the chi(1)
      torsion angle of the aromatic residue in position i depended on the direction of
      the Ar-HN interaction. The position of the aromatic ring in Ar(i)-HN(i + 1, i +
      2, and i + 3) interactions was mostly trans, in Ar(i)-HN(i - 1, i - 2, and i - 3)
      interactions mainly gauche(-), and in Ar(i)-HN(i) interactions mostly gauche(+).
      The analyses of the secondary structures of the protein fragments containing Ar
      HN interactions showed that Ar-HN interactions were in all types of secondary
      structures. Search results suggest that Ar-HN interactions have a stabilizing
      effect on all types of secondary structures.

PMID- 11340655
TI  - Theoretical evidence of a salt bridge disruption as the initiating process for
      the alpha1d-adrenergic receptor activation: a molecular dynamics and docking
      study.
AB  - This study reports the building of the three-dimensional structure of the rat
      alpha1d-adrenergic receptor through a topology approach based on the structure of
      the rhodopsin receptor from cryoelectron microscopy. The validity and reliability
      of the receptor model were assessed through exhaustive molecular dynamics and
      docking studies. Some interesting ligand-receptor interactions were identified
      along with significant differences between the binding mode of agonists and
      antagonists. The importance of the disruption of a salt bridge as a possible
      initial event leading to receptor activation is discussed on the basis of data
      from mutagenesis and molecular dynamics studies.

PMID- 11340656
TI  - Free energy barrier estimation of unfolding the alpha-helical surfactant
      associated polypeptide C.
AB  - Molecular dynamics simulations were conducted to estimate the free energy barrier
      of unfolding surfactant-associated polypeptide C (SP-C) from an alpha-helical
      conformation. Experimental studies indicate that while the helical fold of SP-C
      is thermodynamically stable in phospholipid micelles, it is metastable in a mixed
      organic solvent of CHCl3/CH3OH/0.1 M HCl at 32:64:5 (v/v/v), in which it
      undergoes an irreversible transformation to an insoluble aggregate that contains
      beta-sheet. On the basis of experimental observations, the free energy barrier
      was estimated to be approximately 100 kJ/mole by applying Eyring's transition
      state theory to the experimental rate of unfolding [Protein Sci 1998;7:2533
      2540]. These studies prompted us to carry out simulations to investigate the
      unwinding process of two helical turns encompassing residues 25-32 in water and
      in methanol. The results give an upper bound estimation for the free energy
      barrier of unfolding of SP-C of approximately 20 kJ/mole. The results suggest a
      need to reconsider the applicability of a single-mode activated process theory to
      protein unfolding.

PMID- 11340657
TI  - Optimizing the hydrogen-bond network in Poisson-Boltzmann equation-based pK(a)
      calculations.
AB  - pK(a) calculation methods that are based on finite difference solutions to the
      Poisson-Boltzmann equation (FDPB) require that energy calculations be performed
      for a large number of different protonation states of the protein. Normally, the
      differences between these protonation states are modeled by changing the charges
      on a few atoms, sometimes the differences are modeled by adding or removing
      hydrogens, and in a few cases the positions of these hydrogens are optimized
      locally. We present an FDPB-based pK(a) calculation method in which the hydrogen
      bond network is globally optimized for every single protonation state used. This
      global optimization gives a significant improvement in the accuracy of calculated
      pK(a) values, especially for buried residues. It is also shown that large errors
      in calculated pK(a) values are often due to structural artifacts induced by
      crystal packing. Optimization of the force fields and parameters used in pK(a)
      calculations should therefore be performed with X-ray structures that are
      corrected for crystal artifacts.

PMID- 11340658
TI  - Crystal structure of a mutant human lysozyme with a substituted disulfide bond.
AB  - The three-dimensional structure of a mutant human lysozyme, W64CC65A, in which a
      non-native disulfide bond Cys64--Cys81 is substituted for the Cys65--Cys81 of the
      wild type protein by replacing Trp64 and Cys65 with Cys and Ala, respectively,
      was determined by X-ray crystallography and refined to an R-value of 0.181, using
      33,187 reflections at 1.87-A resolution. The refined model of the W64CC65A
      protein consisted of four molecules, which were related by two
      noncrystallographic twofold axes and a translation vector. Although no specific
      structural differences could be observed among these four molecules, the overall
      B-factors of each molecule were quite different. The overall structure of
      W64CC65A, especially in the alpha-helical domain, was found to be quite similar
      to that of the wild type protein. Moreover, the side-chain conformation of the
      newly formed Cys64--Cys81 bond was quite similar to that of the Cys65--Cys81 bond
      of the wild-type protein. However, in the beta-sheet domain, the main-chain atoms
      of the loop region from positions 66-75 could not be determined, and significant
      structural changes due to the formation of the non-native disulfide bond could be
      observed. From these results, it is clear that the loop region of the mutant
      protein does not fold with the specific folding as observed in the wild-type
      protein.

PMID- 11340659
TI  - Mechanism of NAD(P)H:quinone reductase: Ab initio studies of reduced flavin.
AB  - NAD(P)H:quinone oxidoreductase type 1 (QR1, NQO1, formerly DT-diaphorase; EC
      1.6.99.2) is an FAD-containing enzyme that catalyzes the nicotinamide nucleotide
      dependent reduction of quinones, quinoneimines, azo dyes, and nitro groups.
      Animal cells are protected by QR1 from the toxic and neoplastic effects of
      quinones and other electrophiles. Alternatively, in tumor cells QR can activate a
      number of cancer chemotherapeutic agents such as mitomycins and
      aziridylbenzoquinones. Thus, the same enzyme that protects the organism from the
      deleterious effects of quinones can activate cytotoxic chemotherapeutic prodrugs
      and cause cancer cell death. The catalytic mechanism of QR includes an important
      initial step in which FAD is reduced by NAD(P)H. The unfavorable charge
      separation that results must be stabilized by the protein. The details of this
      charge stabilization step are inaccessible to easy experimental verification but
      can be studied by quantum chemistry methods. Here we report ab initio quantum
      mechanical calculations in and around the active site of the enzyme that provide
      information about the fine details of the contribution of the protein to the
      stabilization of the reduced flavin. The results show that (1) protein
      interactions provide approximately 2 kcal/mol to stabilize the planar
      conformation of the reduced flavin isoalloxazine ring observed in the X-ray
      structure; (2) the charge separation present in the reduced planar form of the
      flavin is stabilized by interactions with groups of the protein; (3) even after
      stabilization, the reduction potential of the cofactor remains more negative than
      that of the free flavin, making it a better reductant for a larger variety of
      quinones; and (4) the more negative reduction potential may also result in faster
      kinetics for the quinone reduction step.

PMID- 11340660
TI  - Fluctuations in ion pairs and their stabilities in proteins.
AB  - This report investigates the effect of systemic protein conformational
      flexibility on the contribution of ion pairs to protein stability. Toward this
      goal, we use all NMR conformer ensembles in the Protein Data Bank (1) that
      contain at least 40 conformers, (2) whose functional form is monomeric, (3) that
      are nonredundant, and (4) that are large enough. We find 11 proteins adhering to
      these criteria. Within these proteins, we identify 22 ion pairs that are close
      enough to be classified as salt bridges. These are identified in the high
      resolution crystal structures of the respective proteins or in the minimized
      average structures (if the crystal structures are unavailable) or, if both are
      unavailable, in the "most representative" conformer of each of the ensembles. We
      next calculate the electrostatic contribution of each such ion pair in each of
      the conformers in the ensembles. This results in a comprehensive study of 1,201
      ion pairs, which allows us to look for consistent trends in their electrostatic
      contributions to protein stability in large sets of conformers. We find that the
      contributions of ion pairs vary considerably among the conformers of each
      protein. The vast majority of the ion pairs interconvert between being
      stabilizing and destabilizing to the structure at least once in the ensembles.
      These fluctuations reflect the variabilities in the location of the ion pairing
      residues and in the geometric orientation of these residues, both with respect to
      each other, and with respect to other charged groups in the remainder of the
      protein. The higher crystallographic B-factors for the respective side-chains are
      consistent with these fluctuations. The major conclusion from this study is that
      salt bridges observed in crystal structure may break, and new salt bridges may be
      formed. Hence, the overall stabilizing (or, destabilizing) contribution of an ion
      pair is conformer population dependent.

PMID- 11340661
TI  - Structural implications of drug-resistant mutants of HIV-1 protease: high
      resolution crystal structures of the mutant protease/substrate analogue
      complexes.
AB  - Emergence of drug-resistant mutants of HIV-1 protease is an ongoing problem in
      the fight against AIDS. The mechanisms governing resistance are both complex and
      varied. We have determined crystal structures of HIV-1 protease mutants, D30N,
      K45I, N88D, and L90M complexed with peptide inhibitor analogues of CA-p2 and p2
      NC cleavage sites in the Gag-pol precursor in order to study the structural
      mechanisms underlying resistance. The structures were determined at 1.55-1.9-A
      resolution and compared with the wild-type structure. The conformational disorder
      seen for most of the hydrophobic side-chains around the inhibitor binding site
      indicates flexibility of binding. Eight water molecules are conserved in all 9
      structures; their location suggests that they are important for catalysis as well
      as structural stability. Structural differences among the mutants were analyzed
      in relation to the observed changes in protease activity and stability. Mutant
      L90M shows steric contacts with the catalytic Asp25 that could destabilize the
      catalytic loop at the dimer interface, leading to its observed decreased dimer
      stability and activity. Mutant K45I reduces the mobility of the flap and the
      inhibitor and contributes to an enhancement in structural stability and activity.
      The side-chain variations at residue 30 relative to wild-type are the largest in
      D30N and the changes are consistent with the altered activity observed with
      peptide substrates. Polar interactions in D30N are maintained, in agreement with
      the observed urea sensitivity. The side-chains of D30N and N88D are linked
      through a water molecule suggesting correlated changes at the two sites, as seen
      with clinical inhibitors. Structural changes seen in N88D are small; however,
      water molecules that mediate interactions between Asn88 and Thr74/Thr31/Asp30 in
      other complexes are missing in N88D.

PMID- 11340662
TI  - Multiple protein folding nuclei and the transition state ensemble in two-state
      proteins.
AB  - Using exhaustive simulations of lattice models with side-chains, we show that
      optimized two-state folders reach the native state by a nucleation-collapse
      mechanism with multiple folding nuclei (MFN). For both the full model and the Go
      version, there are certain contacts that on an average participate in the
      critical nuclei with higher probability than the others. The high- (> or = 0.5)
      probability contacts are largely determined by the structure of the native state.
      Comparison of the results for the full sequence and the Go model shows that non
      native interactions compromise the degree of cooperativity and stability of the
      native state. From an extremely detailed analysis of the folding kinetics, we
      find that non-native interactions are present in the folding nuclei. The folding
      times decrease if the non-native interactions in the folding nuclei are made
      neutral or repulsive. Using cluster analysis and making no prior assumption about
      reaction coordinate, we show that both full and Go models have three distinct
      transition states that give a structural description for the MFN. In the
      transition states, on an average, about two-thirds of the sequence is structured,
      whereas the rest is disordered, reminiscent of the polarized transition state in
      the SH3 domain. Our studies show that Go models cannot describe the transition
      state characteristics of two-state folders at the molecular level. As a byproduct
      of our investigations, we establish that our method of computing the transition
      state ensemble is numerically equivalent to the technique based on the stochastic
      separatrix, which also does not require a priori knowledge of the folding
      reaction coordinate.

PMID- 11340663
TI  - Anabaena apoflavodoxin hydrogen exchange: on the stable exchange core of the
      alpha/beta(21345) flavodoxin-like family.
AB  - An important issue in modern protein biophysics is whether structurally
      homologous proteins share common stability and/or folding features. Flavodoxin is
      an archetypal alpha/beta protein organized in three layers: a central beta-sheet
      (strand order 21345) flanked by helices 1 and 5 on one side and helices 2, 3, and
      4 on the opposite side. The backbone internal dynamics of the apoflavodoxin from
      Anabaena is analyzed here by the hydrogen exchange method. The hydrogen exchange
      rates indicate that 46 amide protons, distributed throughout the structure of
      apoflavodoxin, exchange relatively slowly at pH 7.0 (k(ex) < 10(-1) min(-1)).
      According to their distribution in the structure, protein stability is highest on
      the beta-sheet, helix 4, and on the layer formed by helices 1 and 5. The exchange
      kinetics of Anabaena apoflavodoxin was compared with those of the apoflavodoxin
      from Azotobacter, with which it shares a 48% sequence identity, and with Che Y
      and cutinase, two other alpha/beta (21345) proteins with no significant sequence
      homology with flavodoxins. Both similarities and differences are observed in the
      cores of these proteins. It is of interest that a cluster of a few structurally
      equivalent residues in the central beta-strands and in helix 5 is common to the
      cores.

PMID- 11340664
TI  - Simulation of two-dimensional streptavidin crystallization.
AB  - We present lattice Monte Carlo simulations of the growth of streptavidin islands
      at a biotinylated lipid layer. The model employed takes into account attractive
      anisotropic lateral interactions between streptavidin tetramers. With a minimal
      set of interactions, we reproduce the formation of rectangular islands
      experimentally observed at pH > or = 9.0. Specifically, we analyze two scenarios
      of the island growth. First, if streptavidin is rapidly adsorbed at t = 0
      (stepwise coverage change without ongoing adsorption), the average linear island
      size is found to grow according to the Lifshitz-Slyozov law, R proportional to
      t(1/3). Second, if the island growth occurs in parallel with streptavidin
      adsorption limited by diffusion in the solution, the Lifshitz-Slyozov law is also
      applicable, but only at the late stage, when the streptavidin coverage is
      appreciable.

PMID- 11340666
TI  - Comparison of different schemes to treat long-range electrostatic interactions in
      molecular dynamics simulations of a protein crystal.
AB  - Eight molecular dynamics simulations of a ubiquitin crystal unit cell were
      performed to investigate the effect of different schemes to treat the long-range
      electrostatic interactions as well as the need to include counter ions. A crystal
      system was chosen as the test system, because the higher charge density compared
      with a protein in solution makes it more sensitive to the way of treating the
      electrostatic interactions. Three different schemes of treating the long-range
      interactions were compared: straight cutoff, reaction-field approximation, and a
      lattice-sum method (P3M). For each of these schemes, two simulations were
      performed, one with and one without the counter ions. Two additional simulations
      with a reaction-field force and different initial placements of the counter ions
      were performed to examine the effect of the initial positions of the ions. The
      inclusion of long-range electrostatic interactions using either a reaction-field
      or a lattice-sum method proved to be necessary for the simulation of crystals.
      These two schemes did not differ much in their ability to reproduce the
      crystallographic structure. The inclusion of counter ions, on the other hand,
      seems not necessary for obtaining a stable simulation. The initial positions of
      the ions have a visible but small effect on the simulation.

PMID- 11340665
TI  - Expression in Pichia pastoris and characterization by circular dichroism and NMR
      of rhodostomin.
AB  - Rhodostomin (Rho) is a snake venom protein isolated from Calloselasma rhodostoma.
      Rho is a disintegrin that inhibits platelet aggregation by blocking the binding
      of fibrinogen to the integrin alpha(IIb)beta3 of platelets. Rho produced in
      Escherichia coli inhibited platelet aggregation with a K(I) value of 263 nM.
      Although functional, Rho produced in E. coli is misfolded based on our 2D and 3D
      NMR studies. In order to correct the folding problem, Rho was expressed in Pichia
      pastoris. The recombinant Rho expressed in P. pastoris inhibited platelet
      aggregation with a resulting K(I) value of 70 nM. This is the same potency as
      that of native Rho. CD analysis showed that the secondary structures of Rho are
      pH-independent and contain 3.5-7.9% alpha-helix, 48.2-50.5% beta-structures, and
      42.3-47% coil. The sequential assignment and structure analysis of Rho were
      obtained using 2D and 3D 15N-edited NMR spectra. These results provide the first
      direct evidence that highly disulfide-bonded disintegrin can be expressed in P.
      pastoris with the correct fold. This evidence may serve as the basis for
      exploring the structure and function relationships as well as the dynamics of
      disintegrin and its variants.

PMID- 11340667
TI  - A refined accuracy index to evaluate algorithms of protein secondary structure
      prediction.
AB  - Nowadays even a 1% increase of the accuracy for the secondary structure
      prediction is considered remarkable progress. In this case, we have to consider
      the reasonableness of the accuracy index Q3, which is used widely. A refined
      accuracy index, called Q8, is proposed to evaluate algorithms of secondary
      structure prediction. It is shown that Q8 is superior to the widely used index Q3
      in that the former carries more information of the predictive accuracy matrix
      than does the latter. Therefore, algorithms are evaluated more objectively by Q8
      than Q3. Based on 396 nonhomologous proteins, five currently available algorithms
      of secondary structure prediction were evaluated and compared using the new index
      Q8. Of the five algorithms, PHD turned out to be the unique algorithm, with Q8
      accuracy better than 70%. It is suggested that Q3 should be replaced by Q8 in
      evaluating secondary structure prediction in future studies.

PMID- 11340669
TI  - Immunopathogenesis of delayed-type hypersensitivity.
AB  - Cell-mediated immunity is defined as a beneficial host response characterized by
      an expanded population of specific T cells, which, in the presence of antigens,
      produce cytokines locally. The activation and recruitment of cells into an area
      of inflammation is a crucial step in the development of DTH responses. DTH is
      immunologically a process similar to cell-mediated immunity, involving T cells
      and cytokines. CD4 T helper (Th) 1 cells, differentiated from naive Th cells by
      IL-12 and IL-18 produced from macrophages, play a regulatory role in the
      expression of DTH and activation of macrophages via interferon gamma generated by
      Th1 and natural killer cells. Macrophages accumulate at the site of DTH and
      become activated through the CD4 Th1 cell-cytokine-macrophage axis. However, DTH
      leads to pathologic responses, such as granulomatous inflammation, calcification,
      caseation necrosis, and cavity formation. Granulomas usually form as a result of
      the persistence of a nondegradable product or as the result of DTH responses. DTH
      is also required for host defense against etiologic agents, such as Mycobacterium
      tuberculosis. The expression of cell-mediated immunity/DTH is a double-edged
      sword that may contribute to both clearance of the etiologic agent and tissue
      damage.

PMID- 11340670
TI  - Peribronchiolar accumulation of dendritic cells and their close association with
      CD4(+) T cells in the murine lung hypersensitivity.
AB  - In order to understand the interaction between dendritic cells (DCs) and helper T
      (Th) cells in the region exposed to antigens during pulmonary delayed-type
      hypersensitivity (DTH), which is considered to be mediated by Th1 cells, we
      immunohistochemically investigated their spatial relationship in the cellular
      infiltrate. At 24 hours after intratracheal instillation of hapten in sensitized
      mice, DCs were preferentially accumulated around the bronchioles, whereas
      macrophages were more abundant around the accompanying arteries. DCs often formed
      a cluster, in which they were interconnected with each other by projections.
      Serial section analysis revealed that clustered DCs made a close apposition to Th
      cells but much less frequently to cytotoxic T cells and B cells. Immunoelectron
      microscopy demonstrated that lymphocytes extravasated the capillaries in the
      peribronchiolar interstitium and made conjugation with DCs. In the interstitial
      tissue, DCs often adhered to the fibroblasts, suggesting the supportive role of
      the latter cells in DC migration. Eosinophils were also frequent around the
      arteries, representing the possible involvement of Th2 cytokines. By contrast, in
      a chronic type of airway inflammation induced by repeated challenges of
      aerosolized ovalbumin, DCs were densely and diffusely accumulated around the
      arteries in the same way as macrophages. The present study demonstrated a close
      association of DCs with Th cells around the bronchioles during pulmonary DTH,
      suggesting that local interaction between them in the lung may play important
      roles in the development of this disorder.

PMID- 11340671
TI  - Role of dendritic cells and Th2 lymphocytes in asthma: lessons from eosinophilic
      airway inflammation in the mouse.
AB  - Asthma is a chronic disorder of the airways characterized by variable airway
      narrowing, mucus hypersecretion, and infiltration of the airway wall with
      eosinophils. It is now believed that asthma is controlled by Th2 lymphocytes
      producing cytokines such as IL-4, IL-5, IL-9, and IL-13. Animal models of
      eosinophilic airway inflammation and airway hyperreactivity have been developed
      to study the contribution of cells or mediators in the pathogenesis of asthma. In
      this review, we discuss the role of antigen presenting cells, CD4(+) and CD8(+) T
      lymphocytes, B lymphocytes, NK cells, and mast cells in the induction and
      maintenance of eosinophilic airway inflammation, mucus hypersecretion, and airway
      hyperreactivity.

PMID- 11340672
TI  - Distinct function of Th1 and Th2 type delayed type hypersensitivity: protective
      and pathological reactions to chlamydial infection.
AB  - The role of delayed-type hypersensitivity (DTH) to chlamydial infection has been
      shown to be a double-edged sword to the host. Reported animal and human studies
      have, on the one hand, shown that DTH is associated with protective immunity
      against chlamydial infection and, on the other hand, shown links to
      immunopathology. Using a murine lung infection model, we recently demonstrated
      that there might be two different functional types of DTH induced by chlamydial
      infection based on its association with cytokine patterns. Th1 type DTH is
      associated with protection while Th2 type DTH is associated with immunopathology.
      The Th2 type DTH demonstrated in IFNgamma gene knockout (KO) mice is
      characterized by eosinophil infiltration in addition to mononuclear cell
      infiltration that exists in Th1 DTH, observed in wild-type C57BL/6 mice and IL-10
      KO mice. In addition, the inflammatory cells in IFNgamma KO mice fail to target
      the cellular sites of chlamydial inclusions in infected tissues and fail to clear
      the infection. The functional differences in Th1 and Th2 type DTH responses may
      account for the dual role DTH plays in chlamydial protective immunity and
      immunopathology.

PMID- 11340673
TI  - Alveolar macrophage-T cell interactions during Th1-type sarcoid inflammation.
AB  - Sarcoidosis is an immunomediated, multisystem disorder of unknown cause(s)
      characterized by a heightened Th1 immune response that leads to an uncontrolled
      granuloma formation at sites of disease activity. The past few years have seen
      outstanding advances in the understanding of immunological and molecular events
      involved in the pathogenesis of this disease. The idea is that several cytokines
      and chemokines, which are secreted at sites of disease activity, participate in
      granuloma formation. This paper describes recent data that have clarified some of
      the events that govern the development of the hypersensitivity reaction during
      sarcoidosis. In particular, we will review recent evidence indicating that a
      complex relationship exists between the macrophage/lymphocyte cellular axis and
      the tissue networks of cytokines.

PMID- 11340674
TI  - Role of monocyte chemoattractant protein-1 in Propionibacterium acnes-induced
      pulmonary granulomatosis.
AB  - The inflammatory process in granulomatous disorders such as sarcoidosis is mainly
      the consequence of delayed hypersensitivity induced by causative antigens.
      Propionibacterial DNA was isolated recently by PCR from human sarcoidosis tissue.
      Hence, we developed a model using sensitized rabbits for T cell-mediated
      pulmonary granulomatosis induced by Propionibacterium acnes (P. acnes) and
      investigated the role of monocyte chemoattractant protein-1 (MCP-1) in the
      pathogenesis of the granuloma formation in vivo. Intravenous injection of P.
      acnes into sensitized rabbits induced massive pulmonary granulomas on day 3.
      Maximum levels of MCP-1 in sera and bronchoalveolar lavage fluid (BALF) were
      detected on day 1 and preceded recruitment of monocyte/macrophages and T cells.
      In BALF, monocyte chemotaxis peaked 1 day after P. acnes challenge, and T cell
      chemotaxis peaked 3 days after P. acnes challenge. Anti-MCP-1 IgG inhibited
      monocyte chemotaxis by 80.2% and T cell chemotaxis by 35.7%. Phenotypic analysis
      of migrating T cells revealed that activated and memory T cells
      (CD26(+)/CD45RO(+)) but not naive cells were preferentially attracted to BALF.
      Administration of MCP-1 antiserum in vivo inhibited the development of granulomas
      in both size 59.9% reduction and number 28.6% reduction, the number of
      infiltrating leukocytes in BALF, and the expression of adhesion molecules on
      leukocytes in peripheral blood and BALF. Our data indicate that MCP-1 plays
      important roles in granuloma formation by attracting and activating specific
      types of cells in this model. Furthermore, results suggest that the rabbit model
      resembles human angiocentric granulomatosis and would be useful for investigating
      the immunopathogenesis of human pulmonary granulomatosis.

PMID- 11340675
TI  - III. Chemokines and other mediators, 8. Chemokines and their receptors in cell
      mediated immune responses in the lung.
AB  - Chemokines constitute a large family of chemotactic cytokines that belong to a
      super-gene family of 8-10 kDa proteins. The chemokines are considered to be
      primarily beneficial in host defense against invading pathogens. However, the
      reactions induced by chemokines can be occasionally excessive, resulting in a
      harmful response to the host. Recent studies in chemokine biology have elucidated
      that chemokines are involved in the initiation, development, and maintenance of
      numbers of diseases including lung diseases. In addition to its chemotactic
      activity, evidence suggests that chemokines can modify the outcome of the cell
      mediated immune responses by altering the Th1/Th2 cytokine profile. Chemokines
      are also capable of dictating the direction of specific immune responses.
      Chemokine action is mediated by a large super-family of G-protein coupled
      receptors, and the receptors are preferentially expressed on Th1/Th2 cells.
      Certain chemokine receptors are constitutively expressed in immune surveying
      cells such as dendritic cells and naive T cells. The corresponding chemokines are
      present in normal lymphoid tissues, suggesting a role of chemokines/receptors in
      cell homing and cell-cell communication in lymphoid tissue that can be an initial
      step for immune recognition. Thus, comprehension of the chemokine biology in
      immune responses appears to be fundamental for understanding the pathogenesis of
      T cell-mediated immune responses. The following review will highlight the current
      insight into the role of chemokines and their receptors in the cell-mediated
      immune response, with a special focus on lung diseases.

PMID- 11340676
TI  - IV. Clinical aspects of delayed hypersensitivity in lungs: pathophysiology of
      hypersensitivity disorders in clinics.
AB  - Hypersensitivity pneumonitis (HP) is an immunologically mediated lung disease of
      inhaled antigens. HP is not a uniform disease but rather a clinical complex
      syndrome characterized by varying intensities of responsiveness to different
      organic antigens. The main aetiological agents include thermophilic bacteria,
      fungi, animal proteins, and chemical compounds. A combination of host and
      environmental factors should be considered as a requisite to developing this
      disease. Although the antigens differ widely, the clinical syndromes that results
      are very similar. HP occurs mainly in non-smokers, and clinically it may be in
      acute, subacute, or chronic forms. The diagnosis of HP requires a constellation
      of clinic, radiographic, physiologic, pathologic, and immunologic criteria. HP is
      characterized by a diffuse and predominantly mononuclear cell inflammation, a
      partly granulomatous, immune disorder of alveolar regions that often involves the
      small airway. A strong evidence supports that delayed cell-mediated
      hypersensitivity mechanisms play a role in pathogenesis of HP. Studies performed
      on lung cells have demonstrated that cells bearing suppressor/cytotoxic phenotype
      characterize the lymphocytic alveolitis in patients with hypersensitivity
      pneumonitis. And also recently evidence has been provided indicating that a
      prominent role of T-helper 1 cell-mediated hypersensitivity with an imbalance in
      T-lymphocyte subsets, although the deposit of immune complex may participate in
      an acute form of the disease as well as in the early phase of the chronic form.

PMID- 11340677
TI  - Enhanced resolution of membranes in cultured cells by cryoimmobilization and
      freeze-substitution.
AB  - Investigations of cellular processes demand immediate arresting of the process at
      any given time and excellent retention of cellular material and excellent
      visibility of membranes. To achieve this goal we used cryofixation to arrest
      cellular processes instantly and tested diverse freeze-substitution protocols.
      Madin-Darby kidney cells and Vero cells were grown on carbon-coated sapphire
      disks. For cryofixation the sapphire disks covered with a cell monolayer were
      injected with the aid of a guillotine into liquid propane or ethane or a mixture
      of both cooled by liquid nitrogen. Freezing of the cryogen was prevented by using
      a partially insulated cylinder and by vigorous stirring that results in a
      substantial decrement of the freezing point of the cryogen. Cell monolayers can
      be cryofixed successfully using the guillotine in a safety hood at ambient
      temperature and humidity or at 37 degrees C and 45% humidity. The freezing unit
      can also be placed in a laminar flow for working under biohazard conditions. For
      visualizing cell membranes at high contrast and high resolution, cells were
      substituted in the presence of various concentrations of glutaraldehyde and
      osmium tetroxide and the temperature was raised to diverse final temperatures.
      Substitution for 4 hours at -90 degrees C in anhydrous acetone containing 0.25%
      anhydrous glutaraldehyde and 0.5% osmium tetroxide followed by a temperature rise
      of 5 degrees C/hour to 0 degrees C and final incubation for 1 hour at 0 degrees C
      resulted in high contrast and excellent visibility of subcellular components at
      the level of the membrane bilayer. The high spatial and temporal resolution makes
      this methodology an excellent tool for studying cell membrane-bound processes,
      such as virus-cell interactions.

PMID- 11340678
TI  - Bronchoalveolar inflammation following airway infection in preterm infants with
      chronic lung disease.
AB  - Chronic lung disease (CLD) of the newborn is associated with pulmonary
      inflammation. However, the origin of this inflammation is not known. We evaluated
      the impact of airway infection on bronchoalveolar inflammation in mechanically
      ventilated preterm infant at risk for CLD (n = 68). Mean and maximum
      concentrations of the inflammatory mediators (IM) interleukin-1 and interleukin-8
      were assayed in the tracheobronchial aspirate fluid (TAF) of neonates with
      perinatal airway infection (Ureaplasma urealyticum, or bacteria), postnatal
      nosocomial airway infection, or respiratory disease without airway infection from
      days 1-10 of postnatal age. Patients with CLD (n = 23;) exhibited increased
      levels of IM in TAF compared to neonates without CLD. Within the three subgroups,
      concentrations of IM were increased in CLD patients with perinatal infection and
      in CLD patients with respiratory disease without airway infection, but not in CLD
      patients with nosocomial airway infection. Although airway colonization with Gram
      negative bacteria was more frequently found in CLD patients within the first
      month of life, there were no differences between levels of IM in patients
      colonized with Gram-negative bacteria or coagulase-negative staphyloccoci. We
      conclude that perinatal infections with Ureaplasma urealyticum or bacteria and
      respiratory disease without infection, but not nosocomial airway infection,
      contribute to the bronchopulmonary inflammatory response in neonates with CLD.

PMID- 11340679
TI  - Lung development: number of terminal bronchiolar duct endings and gas exchange
      surface area in victims of sudden infant death syndrome.
AB  - Previous research has demonstrated impaired renal development, particularly with
      respect to glomerular number, in victims of sudden infant death syndrome (SIDS).
      The present study used stereological principles to estimate the volume of the
      upper lobe of the right lung, total number of terminal bronchiolar duct endings
      (TBDE), and gas exchange surface area of this lobe within a group of human
      infants. The infants were classified according to cause of death (SIDS or non
      SIDS), and further subdivided according to birth-weight: normal birth-weight
      (NBW) or low birth-weight (LBW). The results demonstrated that TBDE density was
      significantly reduced in SIDS compared to non-SIDS (P = 0.014), but only reduced
      from non-SIDS NBW values in the SIDS NBW group (P = 0.044). Total TBDE number was
      significantly reduced in SIDS from non-SIDS (P = 0.001), and was significantly
      reduced from non-SIDS NBW values in SIDS NBW (P = 0.023). Mean gas exchange
      surface area per TBDE was significantly increased in SIDS compared to non-SIDS
      cases (P = 0.049). The results of the present study indicate developmental delay
      of the lung in SIDS NBW infants who had previously not been considered growth
      retarded based on their normal body parameters.

PMID- 11340680
TI  - Progressive lung and cardiac changes associated with pulmonary hypertension in
      the fetal rat.
AB  - To determine the natural history of lung vascular remodeling and cardiac changes
      in the rat model of persistent pulmonary hypertension syndrome (PPHN) of the
      newborn, we studied fetal rats subjected to maternal indomethacin administration
      initiated on day 19 of gestation and continued for 2, 3, or 4 days. Animals
      receiving a similar volume of water or alcohol served as controls. Significant
      pulmonary hypertension was noted in the experimental group, as evidenced by a
      significantly increased right to left ventricular wall ratio to 1.6 +/- 0.1 in
      the 4-day treatment group, as compared with 1.2 +/- 0.4 in the control group (P <
      0.01). The smooth muscle area for <25 microm external diameter arterial vessels
      was significantly increased (12.7 +/- 0.6 vs. 10.0 +/- 0.6 microm; P < 0.01) and
      the adventitial area of all diameters vessels was significantly greater (P <
      0.01) following 3 days of indomethacin treatment, as compared with water
      controls. Associated with these changes, the 4-day treatment group's lung/body
      weight ratio was 0.021 +/- 0.001, and was significantly less (P < 0.01) than for
      the control group (0.035 +/- 0.001). This reduction in lung weight was not
      associated with changes in lung protein content or wet/dry weight ratio,
      indicating that pulmonary hypertension in the fetal rat induced lung hypoplasia.
      In conclusion, closure of the ductus arteriosus in the fetal rat results in early
      onset right ventricular hypertrophy, followed by pulmonary vascular remodeling
      and lung hypoplasia. We speculate that lung growth in late gestation is adversely
      affected by pulmonary hypertension.

PMID- 11340681
TI  - Prospective longitudinal study of urinary eosinophil protein X in children with
      asthma and chronic cough.
AB  - Airway inflammation is the principal abnormality in asthma and many other
      respiratory diseases. Eosinophils are the cells primarily involved in this
      process. The aim of this study was to analyze sequential changes in urinary
      eosinophil protein X (EPX) a biological marker of eosinophil activation in
      asthmatic children and chronic coughers, and to confirm the importance of such
      changes in evaluating the inflammatory process once regular treatment was
      initiated. Eighty-eight asthmatic children (AC), 33 children with chronic cough
      (CC), and 34 control children were included in the study. All those with
      respiratory disease underwent allergy tests (serum total IgE, serum-specific IgE
      for common allergens, peripheral blood eosinophil (PBE), and skin prick tests)
      and a pulmonary function test (PFT), and had chest X-ray and serum eosinophil
      cationic protein (s-ECP) and urinary EPX assays. All subjects attended the
      outpatient clinic every 3 months, irrespective of the treatment prescribed
      following inclusion in this investigation. At baseline, urinary EPX
      concentrations were higher in children with asthma and those with chronic cough
      than in controls (mean 171.1 and 131.3, respectively, vs. 60.2 microg/mmol
      creatinine, P < 0.001). CC children had lower eosinophil counts (0.25 vs. 0.39 x
      10(9)/L, P < 0.02) than those with asthma. There was no significant difference
      between the AC and CC groups in urinary EPX and s-ECP levels. s-ECP
      concentrations were significantly higher (P < 0.01) in atopic vs. nonatopic
      patients (44 vs. 29.9 ng/mL), but no significant difference was observed for
      urinary EPX. Concentrations of urinary EPX were significantly correlated with s
      ECP levels (r = 0.24, P < 0.025) and with PBE (r = 0.38, P < 0.01). No
      correlation was found between urinary EPX values and PFT results. In AC receiving
      inhaled steroids after the start of the study, there was a significant reduction
      after 3 months in urinary EPX (-54, P < 0.02). In contrast, there was no
      significant change in PBE levels. Urinary EPX concentrations are sensitive,
      noninvasive technique that could be useful to the clinician in the evaluation of
      manifestations of airway inflammation.

PMID- 11340682
TI  - Cystic fibrosis-related deaths in infancy and the effect of newborn screening.
AB  - Although newborn screening for cystic fibrosis (CF) is widely advocated, hard
      evidence in its favor is difficult to obtain, partly because of a dramatically
      improved life expectancy. Between 1985--1989 infants, born in Wales and the West
      Midlands were randomized to newborn CF screening by heel-prick immunoreactive
      trypsin (IRT) measurement or diagnosis by clinical presentation. Eligible
      children with CF who died in the first 5 years of life were identified from the
      local pediatricians and from the National UK CF Survey. In all, 230,076 infants
      were randomized to be screened, while 234,510 were unscreened. One hundred
      seventy-six CF children were identified, of whom 7 died in the first 5 years of
      life, 3 having presented with meconium ileus. Median age of diagnosis in the
      screened group was 8 weeks. On an intention to treat analysis, all 4 nonmeconium
      ileus-related deaths occurred in the unscreened group (Fisher's exact test, P <
      0.05). However, the clinical presentation of 2 of these infants led to them being
      diagnosed prior to 8 weeks, i.e., earlier than would have been likely by
      screening. In conclusion, newborn screening has the potential to decrease infant
      CF deaths, but if it is to be successful, identification and treatment must occur
      as soon as possible after birth.

PMID- 11340683
TI  - Efficacy of once-daily tobramycin monotherapy for acute pulmonary exacerbations
      of cystic fibrosis: a preliminary study.
AB  - Our objective was to compare the efficacy, safety, and microbiology of once-daily
      intravenous (IV) tobramycin with conventional 8-hourly tobramycin/ceftazidime IV
      therapy for acute Pseudomonas aeruginosa (PA) pulmonary exacerbations in cystic
      fibrosis (CF). CF patients with PA-induced pulmonary exacerbations were allocated
      to receive either once-daily tobramycin (Mono) or conventional therapy with
      tobramycin/ceftazidime given 8-hourly (Conv). The two longitudinal groups
      received therapy in a double-blind, randomized manner over a period of 2 years.
      Tobramycin doses were adjusted to achieve a daily area under the time
      concentration curve of 100 mg x hr/L in both groups. Results were assessed for
      both short-term changes (efficacy and safety after 10 days of IV antibiotics
      during acute exacerbations) and long-term changes (efficacy, safety, and sputum
      microbiology between study entry and exit). Pulmonary function tests (PFTs) on
      admission were similar in both groups. After 10 days of IV antibiotics, absolute
      mean improvements in percent of predicted PFTs were 12.8, 12.1, and 13.7 for
      forced expiratory volume in 1 sec (FEV(1)), forced vital capacity (FVC), and
      forced expired flow between 25--75% of FVC (FEF(25--75%)) in the Conv group (n =
      51 admissions) compared to 10.6, 9.9, and 10.6 in the Mono group (n = 47)(P<0.05
      for all). Sixteen percent in the Conv group and 15% of patients in the Mono group
      did not respond to therapy by day 10. Long-term PFT patterns were similar for the
      Conv and Mono groups. The time between admissions did not differ. The Mono group
      showed a significant increase in tobramycin minimum inhibitory concentrations
      (MICs) against PA from study entry to study exit (P = 0.02, n = 27 strains); this
      failed to reach significance in the Conv group (P = 0.08, n = 25). There was no
      significant increase in the number of isolates, with MIC> or =8 mg/L in both
      groups. No short- or long-term changes in audiology or serum creatinine were
      found in either group. After 10 days of IV therapy, the urinary enzyme N-acetyl
      beta-d-glucosaminidase/creatinine ratios increased in both groups (P0.05). This
      increase was greater in the Conv compared to the Mono group (P < 0.05). We
      conclude that this pilot study indicates once-daily tobramycin therapy to be as
      effective and safe as conventional 8-hourly tobramycin/ceftazidime therapy.
      Combination antibacterial therapy appears to offer no clinical advantage over
      once-daily tobramycin monotherapy. Tobramycin once-daily monotherapy is a
      potential alternative to conventional IV antibacterial therapy which deserves
      further investigation, including the impact on susceptibility of PA to
      tobramycin.

PMID- 11340684
TI  - Use of computerized tomography and chest x-rays in evaluating efficacy of
      aerosolized recombinant human DNase in cystic fibrosis patients younger than age
      5 years: a preliminary study.
AB  - The aim of this study was to evaluate the ability of high-resolution computerized
      tomography (HRCT) of the chest and chest x-rays (CXR) to determine efficacy of
      inhaled recombinant human DNase (rhDNase) in cystic fibrosis (CF) patients
      younger than 5 years of age. A randomized, double-blind, placebo-controlled pilot
      study of 12 patients with CF younger than 5 years of age, attending the
      University of Michigan Cystic Fibrosis Center (Ann Arbor, MI) was conducted. The
      changes in the HRCT and CXR score from baseline to day 100 of therapy were
      assessed using a previously validated scoring system. The mean changes of HRCT
      scores between the rhDNase and placebo groups were found to be significant at the
      95% level, with mean change +/- SE mean of - 1.00 +/- 0.53 and 0.58 +/- 0.24 for
      rhDNase and placebo groups, respectively (P = 0.02). The difference in CXR score
      was not significant between the two groups. An analysis was performed to relate
      HRCT subscores to CXR score; only thickening of the intra-interlobular septae was
      significantly correlated with the total CXR score (r = - 0.7, P < 0.01). There
      was improvement in the parents' assessments of the patients' well-being, with
      improvement in physical activity, decreased cough, sleep quality, and appetite in
      those subjects receiving rhDNase. We conclude that the administration of rhDNase
      was associated with improvement in the HRCT scan in CF patients younger than 5
      years of age. Findings indicate that HRCT of the chest is useful and sensitive in
      studying responses to therapy in patients with CF lung disease. To our knowledge,
      this is the first report of the use of HRCT to assess the effectiveness of a
      therapeutic modality in so young a CF patient population.

PMID- 11340685
TI  - Bronchoscopically administered recombinant human DNase for lobar atelectasis in
      cystic fibrosis.
AB  - Lobar atelectasis is a common complication of cystic fibrosis. The majority of
      cases respond to intravenous antibiotics and chest physiotherapy. In a subgroup
      of patients, atelectasis is resistant to medical therapy, and its persistence in
      the pediatric population is associated with a poor prognosis. Bronchoscopic
      instillation of human recombinant DNase expanded atelectatic lobes in three
      children resistant to at least 2 weeks of medical therapy. This method of
      administration of DNase has been successful in resistant cases of lobar
      atelectasis in patients with chronic obstructive pulmonary disease, quadriplegia,
      and status asthmaticus. Purulent cystic fibrosis sputum has a very high DNA
      content, and DNA has been shown to become more pourable in vitro when treated
      with rhDNase. Bronchoscopic instillation of rhDNase should be considered in cases
      of persistent lobar atelectasis unresponsive to medical therapy.

PMID- 11340686
TI  - Lung volume reduction surgery in lieu of pneumonectomy in an infant with severe
      unilateral pulmonary interstitial emphysema.
AB  - A male infant with a prenatal diagnosis (at 20 weeks' gestation) of cystic
      adenomatoid malformation was delivered after 38 weeks' gestation (birth weight, 3
      kg) and admitted to the neonatal intensive care unit. During the first few days
      of life, he developed mild respiratory distress; a chest radiograph and computed
      tomography scan showed multiple cystic areas in the left lower lobe with
      hyperinflation and herniation of the upper lobe across the midline. At 3 weeks of
      age, a left lower lobectomy was performed for presumed cystic malformation. To
      our surprise the pathology reports revealed pulmonary interstitial emphysema. The
      postoperative chest radiograph was unchanged, and mechanical ventilation was
      necessary and required progressively increasing ventilatory settings to provide
      adequate support. High-frequency oscillatory ventilation and selective right
      bronchus intubation failed to improve lung function. After 3 weeks, a left
      thoracotomy was repeated and lung volume reduction was performed with removal of
      50' of the peripheral hyperinflated parenchyma. Postoperative recovery was rapid;
      the child was weaned from the ventilator after 3 days and discharged after 3
      weeks. Follow-up chest X-rays showed a normally expanded right lung with
      mediastinal structures back to midline and a small left lung. Favorable results
      persisted at 3 years of follow-up. This first and successful experience with lung
      volume reduction in a neonate suggests that infants who need removal of a large
      portion of lung parenchyma to achieve adequate ventilation and gas exchange, lung
      volume reduction surgery should be considered as an alternative to pneumonectomy.

PMID- 11340687
TI  - Bronchiolitis obliterans organizing pneumonia (BOOP) in a child with mild-to
      moderate asthma: evidence of mast cell and eosinophil recruitment in lung
      specimens.
AB  - Bronchiolitis obliterans with organizing pneumonia (BOOP) is rarely described in
      children and little is known about its pathogenesis. This paper reports on an 11
      year-old patient suffering from mild-to-moderate asthma. He presented with a
      retrocardiac density at chest computed tomography scan that was slow to resolve
      and failed to respond to antibiotic therapy. Open lung biopsy revealed a
      histological picture with buds of granulation tissue in respiratory bronchioles
      and alveolar ducts, with organized extensions into the alveoli. The use of
      monoclonal antibodies on biopsy specimens demonstrated the presence of an
      inflammatory process affecting not only the thickened alveolar walls, but also
      the remaining lung parenchyma, the pulmonary arteries, and the bronchioles. The
      inflammatory infiltrate consisted mainly of mast cells and eosinophils. The
      clinical condition improved with steroid therapy. To the best of the authors'
      knowledge, this is the first report of BOOP in an asthmatic child with
      recruitment of mast cells and eosinophils documented by using monoclonal
      antibodies.

PMID- 11340688
TI  - Anterior skull base trauma during endoscopic sinus surgery for nasal polyposis
      preferred sites for iatrogenic injuries.
AB  - OBJECTIVE: To determine typical locations for traumatic lesions of the anterior
      skull base during endoscopic sinus surgery. STUDY DESIGN: In this retrospective
      study 12 patients were included who had undergone endoscopic sinus surgery for
      nasal polyposis and were referred to the author for revision surgery after
      iatrogenic trauma of the anterior skull base during the procedure. Each patient
      had been operated by a different surgeon, all of the physicians being in an
      advanced stage of their surgical career and being board certified
      otolaryngologists. RESULTS: During endoscopically controlled revision surgery,
      all lesions could be detected, 10 of them being located in the ethmoid roof,
      while one injury had occurred in the lateral lamella of the cribriform plate and
      another one in the olfactory groove between the medial turbinate and the nasal
      septum. CONCLUSION: In contrast to reports in the literature, the preferred site
      for anterior skull base injuries during endoscopic sinus surgery in our group was
      not the lateral lamella of the cribriform plate, but the anterior part of the
      ethmoid roof, just behind the frontal recess. Apparently the course of the
      ethmoid roof might be misinterpreted during sinus surgery even by surgeons who
      are familiar with the operative technique.

PMID- 11340689
TI  - The effect of intranasal budesonide spray on mucosal blood flow measured with
      laser Doppler flowmetry.
AB  - BACKGROUND: Recent reports have shown that, although rare, findings of mucosal
      ulcers and perforations of the nasal septum in some cases may be associated with
      the use of topical nasal glucocorticosteroids (GCS). It can been speculated that,
      a reduction in septal mucosal blood flow causing ischemia may eventually induce
      septal perforations. AIM: To evaluate whether a single dose of a potent nasal GCS
      given in a clinically recommended dose may acutely reduce the mucosal blood flow
      on the nasal septum. METHODS: Six healthy subjects received in a randomised
      double blind placebo controlled crossover procedure one dose of 64 micrograms
      budesonide aqueous nasal spray (Rhinocort aqua, AstraZeneca R&D, Lund, Sweden)
      and placebo. One dose was delivered into each nasal cavity by means of a pump
      spray. As a positive control 140 micrograms of xylometazoline (Nezeril,
      AstraZeneca R&D, Lund, Sweden) was sprayed in the same way, but in an open
      fashion. A wash-out period of at least 3 days followed each session. Blood flow
      was measured on the nasal septum with Laser Doppler flowmetry up to 20 min after
      administration. RESULTS: Budesonide did not affect the nasal septal mucosal blood
      flow as compared to placebo, but xylometazoline reduced the septal mucosal blood
      flow by 60.9 +/- 7.1% measured from baseline values. CONCLUSION: A single dose of
      intranasal budesonide aqueous nasal spray has no acute effects on nasal septal
      mucosal blood flow.

PMID- 11340690
TI  - Local safety of intranasal triamcinolone acetonide: clinical and histological
      aspects of nasal mucosa in the long-term treatment of perennial allergic
      rhinitis.
AB  - Intranasal corticosteroids are increasingly used to treat allergic rhinitis and
      their long-term use is generally safe. However, the long-term safety of each
      molecule should be assessed. The main aim of this multicenter, prospective,
      randomized, open-label study was to evaluate the effect of triamcinolone
      acetonide aqueous intranasal spray on nasal mucosal thickness, macroscopic
      appearance, and mucociliary function. Patients with perennial allergic rhinitis
      were treated with triamcinolone acetonide 220 micrograms/day for six months.
      Nasal biopsies taken before and after treatment were compared with biopsies from
      patients who had been randomized to oral cetirizine 10 mg day or intranasal
      beclomethasone dipropionate 400 micrograms/day. In the evaluable population (n =
      70), there were no significant differences between groups in terms of
      histologically evaluated thickness and endoscopically evaluated macroscopic
      appearance of the nasal mucosa, or indigocarmine saccharine test mucociliary
      function. In the intent-to-treat population (n = 92), there was no difference
      between treatment groups in the incidence of overall adverse events. This study
      indicates that sustained treatment with intranasal triamcinolone acetonide does
      not lead to atrophy of the nasal mucosa or impairment of mucociliary function.

PMID- 11340691
TI  - Accuracy of acoustic rhinometry.
AB  - OBJECTIVES: The objective of this study was to evaluate the ability of acoustic
      rhinometry (AR) (Rhin2100, Rhinometrics, Lynge, Denmark) to accurately determine
      the dimensions (cross-sectional areas and volumes) of the curved and complex slit
      like geometry of the nasal airway. MATERIALS AND METHODS: A plastic model
      representing the replicate of a decongested nasal airway was produced by
      stereolithographic techniques from a 3-D MRI-scan. The exact dimensions of this
      model was determined from a high resolution CT-scan. Dimensions perpendicular to
      the curved course of the acoustic pathway were compared with dimensions inferred
      from parallel sections. The impact of sound loss to the paranasal sinuses and the
      ability to detect posterior volume changes was tested in the same model. RESULTS:
      The error in volume determination was < 14% for the MCA and < 8% for the volumes,
      whereas the error reached 52% for dimensions calculated from parallel sections in
      the coronal plane. The influence of the simulated maxillary sinuses depend
      primarily on the size of the ostia and may represent an important source of error
      for posterior measurements, in particular after decongestion. CONCLUSIONS: The
      accuracy of acoustically derived dimensions of the 3-D model depend on the
      orientation of the planes used to calculate the dimensions of the model. Volume
      estimates based on the smallest cross-sectional areas in points along the
      acoustic pathway correlate well with acoustically derived volumes, whereas single
      cross-sectional areas are more susceptible to error. Sound leakage to patent
      sinus ostia reduce the accuracy of posterior measurements.

PMID- 11340692
TI  - Endonasal and transcanalicular Er:YAG laser dacryocystorhinostomy.
AB  - In the last 10 years different types of lasers were used for
      dacryocystorhinostomy (DCR). Between April 1998 and August 1999, a fibreoptic
      erbium laser DCR was performed on 12 patients. Eight cases were for a presaccal
      stenosis and 4 cases for a postsaccal stenosis. An erbium laser with a specially
      designed handpiece was used endonasaly and transcanaliculary. Preoperative
      epiphora was present in all patients. Double bicanalicular nasal silicone tubes
      were placed during surgery in all cases. The 3 cases of postoperative failure
      included 2 cases of presaccal stenosis and 1 case of the postsaccal group;
      failure manifested with recurrent epiphora/dacryocystitis; the onset of symptom
      recurrence varied from 9 weeks to 11 weeks postoperatively. Laser-assisted DCR
      includes the avoidance of a cutaneous incision, excessive tissue injury, the
      advantage of short operation time and precision. Suitable indications for the
      erbium laser are stenoses in the canaliculi, in the sac, but also for bone
      lacrimal bone cutting.

PMID- 11340693
TI  - Therapy of invasive mucoceles of the frontal sinus.
AB  - Mucoceles of the frontal sinus that extend into the orbits and the anterior
      cranial fossa can, in certain cases, be difficult to manage therapeutically and
      may lead to lethal complications. The surgeon will have to make a decision
      between an endonasal and an extranasal, transfacial procedure to provide an
      adequate access. Between 1995 and 1998 we treated 12 patients suffering from
      invasive mucoceles of the frontal sinus. The mucocele was localized medially in 7
      cases and in the lateral part of the frontal sinus in 5 cases. Five of the
      patients exhibited destruction of the orbital roof and in 7 cases combined
      destruction of the orbital roof and the floor of the frontal sinus were noted.
      The posterior wall of the frontal sinus was destructed in 6 patients, with one
      patient additionally showing partial destruction of the anterior frontal sinus
      wall. The causes of mucocele formation were previous frontal sinus operations (n
      = 8) and frontal sinus fractures (n = 3). In one case the cause remained unknown.
      In 7 cases with a medially localized mucocele the mucocele was marsupialized
      using an endonasal access. The mucoceles with a lateral localization were
      osteoplastically operated via an external access. Here we performed median
      drainage in 3 cases and, in one case each, obliteration and cranialization of the
      frontal sinus. The follow-up period was 2.8 years on average. All patients were
      free of complaints immediately after the operation. Mucocele recurrence or other
      complications did not arise. The cosmetic results were satisfactory in all cases.

PMID- 11340694
TI  - Ultrasound and antral lavage in the examination of maxillary sinuses.
AB  - Two hundred and ninety maxillary sinuses in 206 patients, suspected of having
      acute or prolonged maxillary sinusitis, were examined using ultrasound (US) and
      then irrigated with isotonic saline. The results of the antral lavage and the US
      were compared and various US recording variables were analyzed. The sensitivity
      of US examination to find maxillary sinus secretion was 77% and the specificity
      49%. The distance from the initial echo to the back wall echo (BWE) and the ratio
      of the echo-free area to the distance from the initial echo to the BWE were
      sensitive indicators of the presence of maxillary sinus secretion. The results
      suggest that US is a relatively sensitive method also in the diagnosis of
      prolonged maxillary sinus inflammations. However, its low specificity weakens its
      value in clinical work. The usability of US in the diagnosis of maxillary
      sinusitis can be increased by intermittently controlling US findings by sinus
      puncture. This is of particular importance for general practitioners, but also
      for specialists.

PMID- 11340695
TI  - Reduction of nasal fractures under local anaesthetic.
AB  - Forty five patients with fractured nasal bones underwent nasal fracture reduction
      under local anaesthetic. Patients used linear analog scores to assess pain
      associated with the procedure and satisfaction with the reduction. The surgeon
      also recorded his assessment of the reduction. The patients were reviewed two
      weeks later and the outcome scores repeated. The procedure was well tolerated and
      forty three patients (95.5%) stated they would undergo the same procedure again
      if they fractured their nose in the future. Fifteen patients (33.3%) had
      significant persistent nasal deformities and were listed for septorhinoplasty.
      The results of nasal fracture reduction under localanaesthetic are comparable to
      those obtained under general anaesthetic. The factors that may contribute to poor
      outcomes following reduction of nasal fractures are discussed.

PMID- 11340696
TI  - Primary nasal tuberculosis.
AB  - We present a case of a patient with primary nasal tuberculosis. Although this is
      a rare finding, it should be considered when a patient presents with a nasal
      obstruction. Smears for acid fast bacilli and cultures tend to be negative in
      nasal tuberculosis. Diagnosis is often based on histo- pathologic findings. Nasal
      TB is known to respond well to the regular treatment for (pulmonary)
      tuberculosis.

PMID- 11340697
TI  - Radiological difficulties in the diagnosis of fibrous dysplasia of the sphenoid
      sinus and the cranial base.
AB  - Fibrous dysplasia is a benign disorder of bone. We present the case of a 26-year
      old man with fibrous dysplasia of the sphenoid sinus and the cranial base. The
      presentation and management of this rare condition are discussed highlighting the
      potential for misdiagnosis with MRI.

PMID- 11340698
TI  - The hinged-door composite septal flap as structural support and lining of nasal
      reconstruction by a forehead flap.
AB  - In this paper we describe four patients who underwent extensive nasal surgery for
      carcinoma in the nasal vestibule. Two patients underwent salvage surgery after
      radiotherapy, whereas the other two patients were treated with primary surgery.
      In all cases the nasal defect was reconstructed using a composite hinged-door
      septal flap for structural support and internal lining combined with a paramedian
      forehead flap which supplied the skin coverage. All patients had a pleasing
      aesthetic and good functional result. The combination of a paramedian forehead
      flap with a composite hinged-door septal flap is an excellent reconstruction
      procedure for defects of the lateral nasal wall and alar region.

PMID- 11340699
TI  - Neuroendocrine carcinoma of the sphenoid sinus: a case report.
AB  - The presentation of a neuroendocrine carcinoma in the paranasal sinuses is
      extremely rare. Until now only 25 cases have been reported in the literature. We
      report a case of a 65-year-old male with an atypical carcinoid of the sphenoid
      sinus which seemed to be associated with multiple endocrine neoplasia type 1 (MEN
      1). To the best of our knowledge this is the first report on an atypical
      carcinoid in the sphenoid sinus.

PMID- 11340700
TI  - Pleomorphic adenoma of the nose.
AB  - Pleomorphic adenoma is the most frequent tumor of the major salivary glands. It
      is rarely located in the lacrymal glands and is unusual in the nasal cavity. A
      rare case of a pleomorphic adenoma of the nose is presented along with a review
      of the literature. The use of nasal endoscopy in removing tumors of the nose and
      paranasal sinuses is discussed.

PMID- 11340702
TI  - [Disaffection with university hospital careers].

PMID- 11340701
TI  - Intranasal beclomethasone dipropionate in the treatment of common cold.
AB  - Sinusitis is usually considered a complication of viral rhinitis. Virus
      infections in the upper respiratory tract lead to mucosal swelling, which may
      obstruct paranasal sinus outflow, resulting in infection in the paranasal
      sinuses. Topical nasal steroids have been found beneficial in a variety of acute
      and chronic nasal conditions including allergic and nonallergic rhinitis and
      chronic rhinosinusitis. The purpose of this study was to examine whether the
      intranasal inhalation powder beclomethasone dipropionate (BDP) 400 micrograms/day
      treatment has a beneficial or harmful effect on symptoms and signs of common
      cold, and whether or not it can prevent common cold complications. A total of 54
      patients were randomized, 26 into the placebo-group and 28 into the BDP group.
      During the 14-day follow-up, there were on an average 10.3 symptomatic days in
      the placebo group and 10.7 days in the BDP group (p = 0.72). The use of
      intranasal BDP in the treatment of common cold neither reduced symptoms caused by
      inflammation nor did it shorten the recovery time. On the other hand, because BDP
      does not increase the risk of complications or significantly prolong the recovery
      during the common cold, there is no need to discontinue its use in the patients
      with allergic rhinitis or nasal polyposis.

PMID- 11340703
TI  - [Abdominal compartment syndrome].
AB  - French physicians dealing with abdominal emergencies are not very familiar with
      the abdominal compartment syndrome (ACS). Increased abdominal pressure has
      deleterious consequences on local (intestine, liver, kidney) circulation, leading
      to death in the absence of correct treatment. Abdominal trauma and ruptured
      aortic aneurism are the main causes of ACS. Clinical presentation may be
      misleading: respiratory failure, oliguria or circulatory symptoms are often
      predominant. Abdominal palpation is inefficient for evaluating intra-abdominal
      pressure (IAP); only measurement of cystic pressure allows precise evaluation of
      IAP. Abdominal decompression is the treatment of choice. It must be performed as
      soon as IAP exceeds 25 mmHg. The procedure may be risky with a high incidence of
      severe complications when ischaemic territories are reperfused. Recent data
      underline the importance of compensation of hypovolemia before decompression.
      Abdominal closure may necessitate various techniques (aponevrotomy, Bogota bags,
      etc.). At any rate, IAP must remain low at the end of the procedure. In case of
      suspicion of ACS, early measurement of IAP is mandatory. If pressure is over 25
      mmHg, a decompressive procedure must be initiated.

PMID- 11340704
TI  - [Acute traumatic rupture of the thoracic aorta and its branches. Results of
      surgical management].
AB  - STUDY AIM: The aim of this retrospective study was to report a series of 102
      patients with acute traumatic rupture of the thoracic aorta and its branches
      (TRA) and to evaluate long-term results. PATIENTS AND METHODS: From April 1977 to
      April 2000, 102 patients with RTA were admitted to our unit. Age ranged between
      12 and 74 years (mean age: 33 years). Localisation was: ascending aorta (n = 3),
      aortic arch (n = 1), isthmus (n = 92), descending aorta (n = 1), innominate
      artery (n = 3), and left subclavian artery (n = 2). Associated injuries mainly
      included craniocerebral lesions (n = 76), rib fractures (n = 68), and thoracic (n
      = 38), and abdominal (n = 24) lesions. Average time between trauma and surgery
      was 37 hours. Aortography was used routinely for diagnosis. Five patients were
      inoperable; the procedure was delayed in three patients. In all but two patients
      with rupture of the isthmus, descending aorta and subclavian artery, the
      operation included venous arterial femorofemoral assistance. Rupture was partial
      in 37 patients (37 direct sutures), and complete in 55 patients (40 direct
      sutures). In two cases of left subclavian artery desinsertion, the operation
      included suture of the aortic tear and reimplantation of the artery. In patients
      with rupture of the ascending aorta and aortic arch, surgery was carried out
      under cardiopulmonary bypass with deep hypothermia for aortic arch rupture.
      Repair consisted of direct suture. In patients with rupture of the innominate
      artery, the lesion was treated under cardiopulmonary bypass by direct suture. In
      five cases, abdominal injuries required emergency procedure before aortic repair.
      RESULTS: Four patients died. No postoperative paraplegia occurred. The high
      morbidity rate was in relation to the associated injuries. Among the 93
      survivors, the aortic clinical status was satisfactory in 91 patients (two
      patients were lost to follow-up). Two patients died from cancer and myocardial
      infarction 2 and 7 years later respectively. One patient had prosthetic sepsis
      and was reoperated on with homograft. Angiographic control by aortography (n =
      60) and angioMRI (n = 22) was normal in 76 patients. There were five stenoses at
      the level of the prosthesis, four with a gradient < 20 mmHg and one with a
      gradient > 50 mmHg and one aneurysm at the level of the isthmus. These last two
      patients were reoperated on with good result. CONCLUSION: RTA remains a surgical
      emergency with multiple difficulties. Despite the development of new imaging
      modalities, angiography remains the gold standard for the work-up of these
      patients. Venous arterial femorofemoral assistance with a pump remains the best
      procedure in order to avoid paraplegia and vascular prosthesis implantation when
      possible. Endovascular stent graft insertion, although still under investigation,
      holds tremendous promise for non-surgical treatment of these patients.

PMID- 11340705
TI  - [Outcome of non-operated adrenal masses in 126 patients observed from 1986 to
      1999].
AB  - STUDY AIM: CT scan performed for non-adrenal related symptoms detects an adrenal
      mass or 'incidentaloma' in 0.4 to 4.3% of cases, and most authors advocate a non
      operative policy, after minimal but careful work-up aimed at excluding
      pheochromocytoma and aldosteronoma. The breakthrough of laparoscopic
      adrenalectomy has led some to challenge this attitude. This retrospective study
      focused on the outcome of non-operated adrenal masses. PATIENTS AND METHOD: From
      1986 through 1999, 126 patients (64 men and 62 women) presented with an
      incidental mass of the adrenal fossa, and a non-surgical attitude was elicited.
      Mean size was 36.5 mm in diameter. All patients underwent an in-depth clinical,
      biochemical and imaging work-up. They have been stratified into two groups: group
      I: no contraindication to surgery (n = 95); and group II: contraindication to
      surgery (frail patients, invasive adrenal or metastatic extra-adrenal cancer) (n
      = 31). RESULTS: With a mean follow-up of 4.3 years, 17 patients were lost to
      follow-up (13.5%), including 11/95 in group I; 36 were dead (28.5%), including
      12/95 in group I (no adrenal-related death) and 24/31 in group II; 72 were alive
      and well without operation, including only one in group II; one patient was
      operated for a benign adrenal adenoma removed at the time of surgery for aortic
      aneurysm. CONCLUSION: Careful clinical, biochemical, imaging and nor-iodo
      cholesterol scintigraphy with definite uptake by the adrenal mass, a strong
      indicator of benignancy, allows surgical indication to be postponed, and is
      likely to cancel it if, at one-year follow-up, imaging studies show no change in
      the mass.

PMID- 11340706
TI  - [Duodenal somatostatinoma. Anatomic/clinical study of 12 operated cases].
AB  - STUDY AIM: Duodenal somatostatinomas (DS) are very rare neuro-endocrine tumours.
      The aim of this retrospective and multicentric study was to report the clinical
      and pathological characteristics of these neoplasms in a series of 12 patients
      and to compare them with the literature. PATIENTS AND METHODS: From 1987 to 1998,
      12 patients were operated for a DS. There were seven women and five men ranging
      in age from 23 to 72 years (mean age: 56.6 years). Four patients had an
      associated von Recklinghausen's disease, one of them with multiple endocrine
      neoplasia (MEN type IIa) and medullary carcinoma of the thyroid. The surgical
      procedures were pancreaticoduodenectomy (n = 8), small bowel resection (n = 2),
      inferior gastrectomy (n = 1) and gastrojejunostomy with hepatic metastases
      biopsies (n = 1). The tumour was mainly located on the 2nd duodenum (n = 10),
      with a mean size of 2.7 cm (ranging from 0.4 to 6 cm) and with a pancreatic
      invasion in three patients. A metastatic disease was present at the time of
      diagnosis in eight patients. There were, according to Capella's classification,
      two patients in the groups I and II, and ten patients in group III (83%),
      respectively. RESULTS: There was one postoperative death after a
      pancreaticoduodenectomy. Three patients secondarily died from tumoral
      progression. Eight patients were alive, with a mean follow-up of 84 months
      (ranging from 5 to 290 months), at the end-point of the study. CONCLUSION:
      Duodenal somatostatinomas are rare neuroendocrine, generally non-functioning,
      well-differentiated tumours with a low grade of malignancy. The association with
      the von Recklinghausen's disease is frequent. The clinical somatostatinoma
      syndrome with diabetes, diarrhea and biliary lithiasis is rare. The treatment is
      surgical even with a metastatic disease. The 5-year survival rate is better than
      those of the pancreatic somatostatinomas or the duodenal gastrinomas.

PMID- 11340708
TI  - [Bleeding gastroduodenal ulcer: results of surgical management].
AB  - AIM OF THE STUDY: The aim of this retrospective study was to report the mortality
      and morbidity after surgery for bleeding peptic ulcer while the population is
      aging and while the medical treatment and endoscopic procedures are improving.
      PATIENTS AND METHODS: This retrospective study between 1994 and 1999 included 49
      patients, 15 women, 34 men, aged 72 +/- 14 years. Patients were separated into
      three groups: ten with uncontrollable haemorrhages, 28 with recurrent
      haemorrhages and 11 with persistent haemorrhages. These patients were classified
      ASA II (n = 6), ASA III (n = 20), ASA IV (n = 21) and ASA V (n = 2). The surgical
      procedures for gastric ulcers (n = 5) were resection-oversewing (n = 2) or
      partial gastric resection (n = 3). The surgical procedures for duodenal ulcers (n
      = 44) were oversewing (n = 30), partial gastric resection (n = 10) or exploratory
      duodenotomy (n = 4). RESULTS: The overall postoperative mortality rate was 20.4%
      (10/49). The mortality rate was 40% (4/10) in patients with massive haemorrhage,
      7% (2/28) in patients with recurrent haemorrhage, and 36% (4/11) in patients with
      persistent haemorrhage. There was no significant difference in the mortality rate
      in relation to the surgical procedures. The morbidity rate was 45%, including
      three bleeding recurrences after suture and three duodenal leakages after partial
      gastric resection. CONCLUSION: The morbidity and mortality rate after surgery for
      bleeding peptic ulcer is still high. Recurrent haemorrhages don't worsen the
      prognosis. Delayed surgery for persistent haemorrhage is associated with a severe
      prognosis.

PMID- 11340707
TI  - [Intestinal obstruction in cancer patients: results of palliative surgery].
AB  - OBJECTIVE: The study aim was to investigate predictive factors related to the
      results, in terms of survival and quality of life, of palliative surgery in
      cancer patients presenting with intestinal obstruction. METHODS: A total of 109
      patients already treated for a neoplasm were operated on for intestinal
      obstruction between 1990 and 2000. The investigated prognostic factors were age,
      sex, location of the primary tumour, extension of the cancer at the time of the
      operation and the surgical procedure carried out. The impact on the quality of
      life was assessed by the resumption of intestinal transit and the return home.
      RESULTS: The median survival rate was 64 days and the postoperative mortality
      rate 21%. The quality of life was improved in 65% of the patients. The only
      factors clearly correlated with survival and the success of the operation were
      the aetiological diagnosis of the intestinal obstruction and the type of
      procedure which was possible to carry out. CONCLUSION: Palliative surgery may
      improve the quality of life of a certain number of patients, but it was not
      possible to demonstrate predictive factors for the selection of patients who
      could have the larger benefits of such surgery.

PMID- 11340709
TI  - [Results of tracheal or esophageal resections in invasive thyroid carcinomas].
AB  - STUDY AIM: The aim of this retrospective study was to report results of 21
      tracheal or esophageal resections for invasive thyroid carcinomas. PATIENTS AND
      METHODS: Between January 1988 and August 2000, 21 patients (mean age: 66 years)
      had a tracheal (n = 10) or esophageal (n = 11) resection for involvement by an
      invasive thyroid carcinoma. There were eight undifferentiated carcinomas, 11
      papillary, one follicular and one epidermoid carcinomas. RESULTS: One patient
      died from pulmonary embolism during the postoperative period. Complications were:
      tracheal fistula (n = 2), tracheal stenosis (n = 1), esophageal fistula (n = 2),
      recurrent nerve palsies (n = 8) and hypoparathyroidism (n = 4). Seven patients
      presented local recurrence and seven presented distant metastases. Ten patients
      were alive and ten patients died of their carcinoma. The mean survival in this
      study was 26 months (21 months for anaplastic carcinomas and 41 months for
      differentiated carcinomas). CONCLUSION: Differentiated thyroid carcinomas have to
      benefit from a complete tumoral resection; tracheal or esophageal resection is
      indicated in case of involvement. Anaplastic carcinomas have a poor prognosis;
      complete resection is indicated only for selected patients; radiotherapy and
      chemotherapy are used, because surgery is often impossible.

PMID- 11340710
TI  - [Hydatid cysts of the liver opening in the biliary tract. Report of 64 cases].
AB  - STUDY AIM: The aim of this retrospective study was to report a series of patients
      with hydatid cyst opened in the biliary tract, who were operated in Morocco.
      PATIENTS AND METHOD: From 1991 to 1998, among 250 hydatid cysts of the liver
      operated in the same center, 64 were in communication with the biliary tract
      (25%). There were 39 men and 25 women. The mean age was 34.2 years (range: 6-60).
      The revealing symptoms were abdominal pain, jaundice or cholangitis, but the
      biliary fistula was asymptomatic in more than 50% of the patients. The hydatid
      cysts were recognized by ultrasonography in all the patients but the biliary
      fistula was only suspected in 17 patients. The surgical procedure included
      drainage and sterilization of the cyst, resection of the protruding wall of the
      cyst (84.4%), unblockage of the main hepatic duct (n = 21) associated with a Kehr
      drainage, and treatment of the bilio-cystic fistula with suture (n = 23) or
      double side drainage (n = 24) or cystobiliary disconnection (n = 15). RESULTS:
      There were two postoperative deaths due to septic shock (n = 1) and
      encephalopathy secondary to a biliary cirrhosis (n = 1). The morbidity rate was
      25%. Among complications, there were four subphrenic abscesses, four prolonged
      biliary leakages and two intestinal obstructions. The main hospital stay was 20
      days. CONCLUSION: The opening of hyatid cysts of the liver into the biliary tract
      may be silent or revealed by biliary symptoms. The results of this series favour
      a conservative procedure, including resection of the protruding wall of the cyst
      and cysto-biliary disconnection, in spite of a high morbidity rate and a long
      hospital stay.

PMID- 11340711
TI  - [Portal hypertension in a patient with hepatitic C revealing an iatrogenic
      arterioportal fistula].
AB  - A 67-year-old man with anti-HCV positive serum, was admitted for hematemesis by
      variceal bleeding. Portal hypertension, which initially was thought to be caused
      by a post-hepatitis C cirrhosis, was due to a fistula between a right hepatic
      artery and a right branch of the portal vein. The fistula located under the right
      liver and the adjacent atrophic hepatic segments, were resected by a bi
      segmentectomy VI-VII. The postoperative course was simple. The pathological study
      of the resected liver showed no cirrhosis but active hepatitis. This
      arterioportal fistula was probably iatrogenic. Sixteen years before, this patient
      had undergone a total gastrectomy for cancer, followed by a serious haemorrhage
      requiring a massive transfusion, which was responsible for the transmission of
      hepatitis C.

PMID- 11340712
TI  - [Adrenocortical tumors with oncocytic cells: benign or malignant?].
AB  - Adrenocortical tumor with oncocytic cells are exceptional. They are composed
      exclusively or almost exclusively of oncocytic cells, which are large cells with
      eosinophilic granulations, corresponding to numerous mitochondria in electronic
      microscopic examination. This tumor is usually non-functional and benign, and has
      to be differentiated from the adrenocortical carcinoma.

PMID- 11340713
TI  - [The history of surgical management of hernias].
AB  - At the dawn of the third millennium, the aim of this brief historical review was
      to trace the evolution of the surgical management of hernias during the recent
      past centuries after the advent of true anatomical knowledge. Because it is a
      frequent and ubiquitous surgery, many surgeons have devised new techniques in
      order to perform more and more efficient procedures, suitable to the patients'
      demands, the health care economy and quality care control.

PMID- 11340714
TI  - [Randomized trial of adjuvant chemotherapy with or without radiotherapy in rectal
      cancers].

PMID- 11340715
TI  - [Factors influencing the functional outcome of restorative proctocolectomy in
      ulcerative colitis].

PMID- 11340716
TI  - Pacifier use and the occurrence of otitis media in the first year of life.
AB  - PURPOSE: The purpose of this study was to assess pacifier use as a risk factor
      for otitis media during the first year of life. METHODS: A volunteer cohort of
      1,375 infants was recruited from eight hospital postpartum units in Iowa. Parents
      were asked to provide detailed information on their child's health at 6 weeks, 3,
      6, 9 and 12 months of age. Questions were posed concerning occurrence of specific
      childhood illnesses, including otitis media, at each time point, as well as other
      factors. RESULTS: Over 70% of children were reported to have experienced one or
      more episodes of otitis media during their first year of life, with its
      occurrence much more common during the second six months. Multivariate analyses
      using Generalized Estimating Equations assessed factors associated with otitis
      media during the entire 12-month period. These analyses showed that pacifier use,
      age, male sex, greater number of childcare days, and higher family incomes were
      significantly associated with occurrence of otitis media. CONCLUSIONS:
      Multivariate analyses found that the occurrence of otitis media was associated
      with pacifier use, one of few modifiable risk factors for otitis media.

PMID- 11340717
TI  - Reasons for dental extractions in children.
AB  - PURPOSE: The purpose of this study was to investigate the principal reason for
      primary tooth extraction and the tooth type most frequently extracted in children
      aged 3-13 years. METHODS: The patients selected for this retrospective study were
      identified by analyzing dental records of children receiving treatment at
      Franciscan Children's Hospital & Rehabilitation Center, Boston, MA (FCH & RC). In
      total, 2,000 records were reviewed, and 567 extracted primary teeth were analyzed
      from 277 patients who had at least one primary tooth extracted under local
      anesthesia. The criteria for inclusion in this study included children between
      the ages of 3 and 13 years. RESULTS: First primary molars were the most common
      tooth type extracted and comprised 30% of teeth removed. Central incisors were
      the next common tooth type extracted and accounted for 25% of the extractions.
      There was no difference, by gender, in the extraction of tooth type but there
      were striking differences according to age. Almost half of the primary teeth
      extracted in subjects 3 to 5 years were incisors, and in patients 6 to 9 years
      the first primary molar was the most common tooth type extracted. Molars were the
      tooth type most frequently extracted from those patients aged 10 to 13 years.
      There were significant differences in the reasons for extraction of various tooth
      types, and, while extractions due to caries predominated overall, this was not
      the case for all tooth types. CONCLUSIONS: This study has concluded that despite
      the dramatic improvements in pediatric oral health over the last decades, caries
      and the resulting pulpal pathology remains the most common reason for extraction
      of primary teeth.

PMID- 11340718
TI  - Antimicrobial effect of fluoride mouthrinse on mutans streptococci and
      lactobacilli in saliva.
AB  - PURPOSE: This study was designed to determine whether the long-term use of
      fluoride mouthrinse affects the salivary levels of mutans streptococci and
      lactobacilli. METHODS: The subjects consisted of 414 school children aged 7, 10,
      and 12 yrs. Among these subjects, 243 children had received fluoride mouthrinse
      since 5 years of age at nursery schools, and comprised the "mouthrinse group."
      The remaining 171 children, the "no mouthrinse group," had not received fluoride
      mouthrinse. All of the children received routine dental health education. The
      levels of mutans streptococci and lactobacilli for the subjects in both groups
      were measured using Dentocult SM Strip mutans and Dentocult LB Dip Slide,
      respectively. Dental examinations were conducted to obtain data on caries
      prevalence (dfs and DMFS). Logistic regression analysis was used to control
      confounding factors: age, dfs, DMFS, frequency of toothbrushing, sum of permanent
      tooth surfaces sealed, frequency of sweet snacks, frequency of sweet drinks, and
      the use of fluoridated toothpaste. RESULTS: There was a significant difference in
      mean DMFS between the mouthrinse group and no mouthrinse group at all ages.
      Children with fluoride mouthrinse had lower levels of mutans streptococci, and
      there was a significant association between the experience of fluoride mouthrinse
      and the score of Dentocult SM strip Odds ratio: 0.64, P < 0.05. However, there
      was no significant relation between the experience of fluoride mouthrinse and the
      score of Dentocult LB Dip Slide. The results of this study demonstrated that the
      long-term use of fluoride mouthrinse affected the detectable levels of mutans
      streptococci, but did not affect the levels of lactobacilli. CONCLUSIONS: These
      results suggest that fluoride mouthrinse might contribute to reducing the number
      of mutans streptococci.

PMID- 11340719
TI  - Indicators of mandibular dental crowding in the mixed dentition.
AB  - PURPOSE: Dental crowding occurring in the anterior part of the mandible in the
      early mixed dentition has been a subject of increasing concern for child
      patients, their parents, and the pediatric dentist. The aim of this study was to
      evaluate indicators of crowding found at the primary dentition, which may lead to
      the future manifestation of crowding at the anterior part of the mandibular arch
      in the early mixed dentition. METHODS: Skeletal and dental morphological
      characteristics at the stage of primary dentition were compared between two
      groups, using dental casts and cephalograms of 23 subjects. These two groups had
      been formed by evaluating the degree of crowding at 9 years of age (12 normal and
      11 crowded cases). RESULTS: The size of several teeth in the crowding group was
      significantly greater than that found in the normal group. For the cephalometric
      measurements, a statistically significant difference was found only in the
      cranial base dimension (S-SE). The stepwise discriminant analysis showed that the
      mesiodistal size of the maxillary primary canine, the maxillary and mandibular
      dental arch lengths, and the posterior cranial base length (S-Ba) were effective
      discriminators in separating the two groups. CONCLUSIONS: It is concluded that
      larger primary tooth size is the chief indicator in the development of dental
      crowding. However, the maxillary and mandibular dental arch lengths and the
      cranial base dimensions, especially that of the posterior cranial base length in
      the primary dentition, should also be considered as indicators when attempting to
      predict dental crowding in the early mixed dentition.

PMID- 11340720
TI  - More rigorous studies needed to advance emerging dental caries diagnostic and
      management strategies, says NIH consensus panel. National Institutes of Health
      Consensus Development Conference. Diagnosis and Management of Dental Caries
      Throughout Life. New release.

PMID- 11340721
TI  - American Board initiates changes in eligibility and candidacy.

PMID- 11340722
TI  - Vertical changes in Class III patients after maxillary protraction with expansion
      in the primary and mixed dentitions.
AB  - PURPOSE: This study determined the vertical response of class III patients in the
      primary, mixed, and late mixed dentition phases fitted with a protraction mask
      and expansion. METHODS: The before and after cephalometric records of 112
      patients divided by sex were analyzed at ages 3 to 6, > 6 to 9 and > 9 to 12
      years to assess the vertical changes. Data was correlated by means of paired t
      tests and scheffe's multiple contrasts. The study showed: (1) descriptive
      statistics and the before and after results in males and females in the different
      age groups; (2) the changes in males and females disregarding age; and (3) the
      changes at the different ages disregarding gender. RESULTS: The main vertical
      changes in this study were seen in the FMA angle, GoGn to SN, Facial axis, and
      ANS-Me between the ages of 3 to 6 years. Between 6 to 9 years, a lesser
      significant opening existed and no significant change could be seen in the GoGn
      SN angular measurement. Between 9 to 12 years all linear and angular measurements
      became non significant with the exception of ANS-Me. CONCLUSIONS: Class III
      corrections should be started as early as possible, once the diagnosis is made
      and cooperation allows it. Most of the changes were seen between the ages of 3 to
      6 years. No significance was seen after the age of 9 years with the exception of
      ANS-Me in both males and females (P < 0.05). No differences were seen between
      males and females in all measurements at the different ages with the exception of
      occlusal plane to SN (P < 0.05) between 3 to 6 years. The vertical changes were
      mostly seen in the mandible with no direct benefit from the changes in the
      midfacial region.

PMID- 11340723
TI  - The investigation of major salivary gland agenesis: a case report.
AB  - Salivary gland agenesis is an extremely uncommon congenital anomaly, which may
      cause a profound xerostomia in children. The oral sequelae includes dental
      caries, candidosis, and ascending sialadenitits. The present report details a
      child with rampant dental caries secondary to xerostomia. Despite having oral
      disease for many years, the congenital absence of all the salivary glands failed
      to be established until early adulthood. The appropriate investigation and
      management of the xerostomic child allows a definitive diagnosis to be made and
      attention focused on the prevention and treatment of resultant oral disease.

PMID- 11340724
TI  - American Board of Pediatric Dentistry Advisory Council: selection, duties, and
      training ground for new directors.

PMID- 11340725
TI  - Aided augmentative communication in managing children with cerebral palsy.
AB  - The use of an aided augmentative communication system to achieve effective
      communication between the pediatric dentist and the child with cerebral palsy is
      described. This type of communication involves symbols placed on a communication
      board and may be used together with conventional behavior management techniques
      for successful delivery of dental treatment. A multidisciplinary team caring for
      the child is necessary to achieve successful outcomes. Aided augmentative
      communication is a promising adjunct for the care of the child with communication
      impairment, and may be of particular value in pediatric dental practices where
      the staff are able to practice and master its use for selected child patients.

PMID- 11340726
TI  - Parotitis as the initial sign of juvenile Sjogren's syndrome.
AB  - Parotid swelling may be associated with a variety of glandular disorders in
      children. This case report describes the characteristic features of juvenile
      Sjogren's syndrome in an adolescent girl who presented with recurrent and
      bilateral parotid gland enlargement. Special emphasis is placed on an age
      specific differential diagnosis for major salivary gland enlargements.

PMID- 11340728
TI  - One-step etch/primer for bracket bonding.
AB  - A single step etch/primer that can be used for bonding orthodontic brackets with
      virtually any light polymerized resin-based composite bracket adhesive material
      that has been introduced. Clinical trials have shown it to be especially useful
      in re-bonding detached metallic or ceramic brackets, and for bonding brackets to
      fluorosed enamel. This technique report describes the PROMPT L-POP* system and
      demonstrates its use.

PMID- 11340727
TI  - Placement of a preformed indirect resin composite shell crown: a case report.

PMID- 11340729
TI  - Anterior esthetic fixed appliances for the preschooler: considerations and a
      technique for placement.
AB  - One of the pediatric dentist's greatest restorative challenges is the esthetic
      rehabilitation of a young toddler who has suffered multiple tooth loss subsequent
      to rampant early childhood caries or extensive dental trauma. An anterior
      esthetic appliance may be used to replace lost teeth. The most decisive factor
      for placing an anterior esthetic appliance is parental desire. Other
      considerations include: space maintenance, masticatory function, speech
      development, and tongue habits. However, there is no strong evidence that early
      loss of maxillary incisors will have any significant, long lasting effect on the
      growth and development of the child. This paper discusses in detail one type of
      fixed anterior esthetic appliance and the considerations to be made when deciding
      when and why to place them.

PMID- 11340730
TI  - Compound odontoma--diagnosis and treatment: three case reports.
AB  - Odontomas are the most common type of odontogenic tumors and generally they are
      asymptomatic. This paper describes three cases of compound odontomas diagnosed in
      children due to dislodgement or over-retention of primary anterior teeth and/or
      swelling of the cortical bone. In all cases, the surgical excision of the lesions
      was performed and, in one case, orthodontic treatment was adopted in order to
      move an impacted permanent tooth to its normal position. The results achieved
      indicate that the early diagnosis of odontomas allows the adoption of a less
      complex and expensive treatment and ensures better prognosis.

PMID- 11340731
TI  - Natal and neonatal teeth: review of the literature.
AB  - Child development from conception through the first years of life is marked by
      many changes. Tooth eruption follows a chronology corresponding to the date when
      the tooth erupts into the oral cavity. These dates have been established in the
      literature and are subjected to small variations depending on hereditary,
      endocrine and environmental features. At times, however, the chronology of tooth
      eruption suffers a more significant alteration in terms of onset, and the first
      teeth may be present at birth or arise during the first month of life. The
      expectations about the eruption of the first teeth are great and even greater
      when the teeth appear early in the oral cavity. The objective of the present
      study was to present a review of the literature with important aspects about
      natal and neonatal teeth.

PMID- 11340732
TI  - Insurance fraud.

PMID- 11340733
TI  - Dentists treating Medicaid-enrolled children.

PMID- 11340734
TI  - Protocols for compassion.

PMID- 11340735
TI  - A national survey of critical care nurses' practices related to administration of
      neuromuscular blocking agents.
AB  - BACKGROUND: Recommendations on use of neuromuscular blocking agents include using
      peripheral nerve stimulators to monitor depth of blockade and concomitantly
      administering sedatives and/or analgesics. OBJECTIVE: To evaluate critical care
      nurses' practices in administering neuromuscular blocking agents. METHODS: A 16
      item survey was mailed to 483 acute care facilities in the United States. Of
      these, 246 surveys (51%) were returned and analyzed to determine use of
      neuromuscular blocking agents, peripheral nerve stimulators, sedatives, and
      analgesics. Logistic regression analysis was used to find independent predictors
      of use of peripheral nerve stimulators. RESULTS: Seventy-five percent of
      respondents reported long-term use of neuromuscular blocking agents in critically
      ill patients. Of those, 63% monitored the level of blockade with peripheral nerve
      stimulators. Reasons for not using peripheral nerve stimulators included
      unavailability of equipment (48%), lack of training (36%), and insufficient
      evidence that peripheral nerve stimulators improve care (23%). Predictors of use
      of stimulators were facilities with more than 150 beds (P < .001) and
      administration of neuromuscular blocking agents by continuous infusion (P <
      .001). Ninety-five percent of respondents reported using concurrent
      analgesics/sedatives always or most of the time. Facilities with fewer than 10
      beds in the intensive care unit used concurrent analgesics/sedatives
      significantly less often than did facilities with 10 beds or more (90% vs 98%,
      respectively; P = .03). CONCLUSIONS: Small and large facilities differ in
      concomitant use of analgesics/sedatives and peripheral nerve stimulators.
      Education and research are needed to ensure that patients receive adequate
      monitoring and sedation during administration of neuromuscular blocking agents.

PMID- 11340736
TI  - A comparison of 2 methods of measuring rectal temperatures with digital
      thermometers.
AB  - BACKGROUND: Digital rectal thermometers typically have 2 distinct modes of
      operation: dwell or monitor, in which body temperature is displayed continuously,
      and predictive, in which body temperature is mathematically estimated on the
      basis of the curve of temperature rise that occurs after the thermometer is
      inserted. Although the dwell mode is generally considered more accurate, the
      predictive mode allows more rapid measurement. Direct comparisons of these 2
      methods are lacking. OBJECTIVE: To determine if measurements of rectal
      temperatures obtained with the predictive mode differ significantly from those
      obtained with the dwell mode. METHODS: For each of 10 subjects, both dwell and
      predictive modes were used to measure early morning rectal temperature. For
      comparison of the 2 modes during states of temperature flux, 8 subjects had
      rectal temperatures measured after swimming in cold water. Initial predictive
      values were measured directly after each subject exited from the water. Initial
      dwell values were estimated by linear extrapolation of measured 3- and 6-minute
      dwell values. Paired-sample statistical methods were used to compare data.
      RESULTS: Measurements of early-morning temperatures obtained with the predictive
      mode did not differ significantly from those obtained with the dwell mode (P =
      .64). Predictive values also did not differ significantly from extrapolated dwell
      values for measurements obtained during mild temperature flux after immersion in
      cold water (P = .33). CONCLUSION: The predictive and dwell modes of digital
      rectal thermometers yield similar measurements of temperature during steady-state
      conditions and during states of mild temperature flux.

PMID- 11340737
TI  - Procedures nurses use to remove central venous catheters and complications they
      observe: a pilot study.
AB  - BACKGROUND: Removal of internal jugular and subclavian central venous catheters
      is a common nursing intervention. Venous air embolism is a serious complication
      of catheter removal. Although some procedures have been recommended to prevent
      venous air embolism, whether nurses use these procedures and what complications
      patients experience are unknown. OBJECTIVES: The purposes of this pilot study
      were (1) to determine what procedures nurses use to remove internal jugular and
      subclavian central venous catheters, (2) to find out what complications patients
      are experiencing, (3) to find out if complications experienced are related to the
      procedures used, and (4) to develop a questionnaire about central venous
      catheters. METHODS: A descriptive and correlational design was used. The subjects
      were 29 nurses whose job description included removal of internal jugular and
      subclavian central venous catheters. Two questionnaires were used: a demographics
      questionnaire and the questionnaire about central venous catheters. RESULTS:
      Descriptive statistics were used to analyze the sample, to determine the
      percentage of nurses sampled who use the recommended procedures, and to describe
      the frequency of complications observed. The sample size was not sufficient for
      observed complications to be correlated with procedures. CONCLUSIONS: None of the
      nurses sampled had venous air embolism diagnosed in their patients. They reported
      observing dyspnea, pain, bleeding from the insertion site, and arrhythmias. Many
      of the nurses reported that they did not always use all the recommended
      procedures; only 9 nurses (31%) reported always using all the recommended
      procedures.

PMID- 11340738
TI  - Sedating critically ill patients: factors affecting nurses' delivery of sedative
      therapy.
AB  - BACKGROUND: Critical care nurses often have wide discretion in managing the
      sedative therapy of patients receiving mechanical ventilation. Little is known
      about the factors and processes that influence sedative practice. OBJECTIVES: To
      determine if nurses' personal beliefs about and attitudes toward critical illness
      and their goals for sedation influence the nurses' sedative practice, to discover
      whether social factors influence sedative therapy, and to describe the processes
      that nurses use to assess patients' need for sedative therapy. METHODS:
      Audiotapes of focus group interviews with 5 groups of 34 experienced medical and
      surgical intensive care unit nurses from 2 hospitals were transcribed verbatim.
      Two investigators independently analyzed the verbatim text, and a sample of the
      participants validated the category summaries and interpretations. RESULTS:
      Patients' family members can affect sedative practice directly or indirectly, and
      demands for efficient delivery of care can influence sedative therapy. Primary
      indications for sedation included patients' comfort and amnesia and prevention of
      patients' self-injurious behaviors. Conflicts between physicians and nurses arose
      when explicit and shared goals for sedation were lacking. Participants noted that
      numerous factors impede routine use of sedation protocols even though use of the
      protocols may improve communication and promote uniformity of sedative practice.
      CONCLUSION: Social, personal, and professional factors influence sedative
      therapy. Future research should establish the relative importance of these
      factors and determine whether their impact is attenuated when sedation protocols
      are implemented.

PMID- 11340739
TI  - Elderly patients' reports of physical restraint experiences in intensive care
      units.
AB  - BACKGROUND: Use of physical restraints has undesirable sequelae. As they weigh
      the risks and benefits of protocols for reducing the use of restraints, staff
      members in intensive care units, where restraints are most used in hospitals,
      need to know how well elderly patients remember being restrained and how patients
      perceive the use of restraints. OBJECTIVES: To estimate the proportion of
      patients who remember being restrained, describe the experience from the
      patients' perspectives, and describe any distress caused by use of restraints
      within the overall experience of being in the intensive care unit. METHODS:
      Transcripts of semistructured, audiotaped interviews of patients who had been in
      the medical or surgical intensive care unit in any of 3 eastern and midwestern
      medical centers were analyzed by question and for overall themes. RESULTS: Six
      patients (40%) remembered some aspect of being restrained but did not report
      great distress. Patients accepted restraints as needed because of the lack of
      alternatives. Patients reported remembering that they should not perform certain
      behaviors but being unable to stop themselves. Patients cited hallucinations and
      intubation as major stressors in the intensive care unit. Patients' continuing
      health problems after discharge from the intensive care unit severely limited
      recruitment of subjects. CONCLUSIONS: Patients do not remember great distress
      specifically related to the use of restraints, but the overall situation leading
      to use of restraints is disturbing if remembered. The discovery of methods to
      reduce the distress of intubation and hallucinations could decrease use of
      restraints.

PMID- 11340740
TI  - Botulism in critical care: a case study in wound botulism.

PMID- 11340741
TI  - Breathing new life into practice communities.

PMID- 11340742
TI  - The critical role of the endothelial cell in acute coronary events.

PMID- 11340743
TI  - Family doctors where they are needed.

PMID- 11340745
TI  - Confession is good for doctors.

PMID- 11340744
TI  - Taking the pulse of Canadian children. Health report card for the millennium.

PMID- 11340746
TI  - Which dose should it be?

PMID- 11340747
TI  - Debate over nurse practitioners.

PMID- 11340748
TI  - Prescription for renewal.

PMID- 11340749
TI  - Close to the seat of power. Conversation with former Federal Cabinet Minister
      John C. Crosbie. Interview by Barbara Kermode-Scott.

PMID- 11340750
TI  - Leflunomide: new antirheumatic drug. Effect on pregnancy outcomes.
AB  - QUESTION: I am treating a 34-year-old woman with rheumatoid arthritis. She began
      taking the new drug leflunomide (Arava) 6 months ago and had good clinical
      response. She is now planning her first pregnancy. What should she do? ANSWER:
      Leflunomide is a new and effective disease-modifying antirheumatic drug. Animal
      studies have shown an increased rate of malformations and fetal death in various
      species, but there are no data on pregnancy outcomes in humans treated with
      leflunomide. Since the drug has a prolonged and unpredictable elimination half
      life, it should be stopped during pregnancy. The manufacturer recommends that
      patients who wish to become pregnant be treated with cholestyramine, which
      enhances elimination.

PMID- 11340751
TI  - Dermacase. Diabetic dermopathy.

PMID- 11340752
TI  - Emergency case. Head injury in patients using warfarin.

PMID- 11340753
TI  - Role of glucocorticoids in treating croup.

PMID- 11340754
TI  - Mental health, job satisfaction, and intention to relocate. Opinions of
      physicians in rural British Columbia.
AB  - OBJECTIVE: To determine the prevalence of depression and burnout among family
      physicians working in British Columbia's Northern and Isolation Allowance
      communities. Current level of satisfaction with work and intention to move were
      also investigated. DESIGN: Cross-sectional, mailed survey. SETTING: Family
      practices in rural communities eligible for British Columbia's Northern and
      Isolation Allowance. PARTICIPANTS: A random sample of family physicians
      practising in rural BC communities. Initial response rate was 66% (131/198
      surveys returned); excluding physicians on leave and in temporary situations and
      those who received duplicate mailings gave a corrected response rate of 92%
      (131/142 surveys returned). MAIN OUTCOME MEASURES: Demographics; self-reported
      depression and burnout; Beck Depression Inventory and Maslach Burnout Inventory
      scores; job satisfaction; and intention to leave. RESULTS: Self-reported
      depression rate was 29%; the Beck Depression Inventory indicated 31% of
      physicians suffered from mild to severe depression. About 13% of physicians
      reported taking antidepressants in the past 5 years. Self-reported burnout rate
      was 55%; the Maslach Burnout Inventory showed that 80% of physicians suffered
      from moderate-to-severe emotional exhaustion, 61% suffered from moderate-to
      severe depersonalization, and 44% had moderate-to-low feelings of personal
      accomplishment. Depression scores correlated with emotional exhaustion scores.
      More than half the respondents were considering relocation. CONCLUSION:
      Physicians working in these communities suffer from high levels of depression and
      very high levels of burnout and are dissatisfied with their current jobs. More
      than half are considering relocating. Intention to move is strongly associated
      with poor mental health.

PMID- 11340755
TI  - Short report: burnout, depression, and moving away. How are they related?

PMID- 11340756
TI  - [Collaboration between family physicians and home care professionals. Is it
      possible?].
AB  - OBJECTIVE: To describe perceptions of physicians and home care professionals
      working in local community service centres (CLSCs) with respect to collaboration
      on home care follow up, and to identify conditions likely to help or hinder
      cooperation. DESIGN: Descriptive study using individual and group interviews.
      SETTING: Areas served by three CLSCs in the Quebec city region. PARTICIPANTS:
      Forty-five general practitioners with large home care practices and coordinators
      and representatives of CLSC home care teams. MAIN OUTCOME MEASURES: Perceptions
      of physicians and home care professionals with respect to interprofessional
      cooperation on and barriers to home care follow up. RESULTS: Most participants
      thought that cooperation would be beneficial to complex case management and
      continuity of follow-up care. In practice, however, cooperation is hindered by
      differences in medical practice and home care team service delivery and in
      methods of remuneration, and lack of knowledge of the other field of practice.
      CONCLUSION: All participants recognized the importance of cooperation. This study
      did not reveal any real integration of medical and CLSC home care services.
      Efforts must be made to identify the strategies most conducive to improving
      interprofessional cooperation.

PMID- 11340757
TI  - [Insomnia. Prevalence and treatment of patients in general practice].
AB  - OBJECTIVE: To evaluate the prevalence of insomnia and the treatments used by
      patients attending general practice clinics. DESIGN: Survey of outpatients.
      SETTING: Quebec city, Que. metropolitan area. PARTICIPANTS: Two hundred eighteen
      patients recruited in waiting rooms of general practice clinics. MAIN OUTCOME
      MEASURES: Participants completed a survey on sleep and use of substances for
      insomnia, a questionnaire documenting their medical history and use of health
      care services, and three indices measuring presence of worry and symptoms of
      anxiety and depression. RESULT: Close to 38% of respondents suffered from
      insomnia: 26.2% had chronic insomnia and 11.4% had short-term insomnia.
      Prevalence was higher among women and people 35 to 54 years old. Among
      respondents who used substances to help them sleep, those 55 years and older
      consumed more prescription and medications (benzodiazepines); those 35 to 54
      years old used mainly natural products; and those 16 to 34 years old consumed
      mainly over-the-counter medications. Respondents suffering from insomnia made
      heavier use of health care services and reported more worry and symptoms of
      anxiety and depression than those who slept well. CONCLUSION: Patients attending
      general practice clinics have a high prevalence of insomnia. Physicians must be
      on the lookout for these sleep disturbances so they can offer appropriate
      treatment.

PMID- 11340758
TI  - Office management of minor wounds.
AB  - OBJECTIVE: To review office interventions for minor wounds not requiring sutures,
      such as abrasions, bites, and lacerations. QUALITY OF EVIDENCE: Most information
      on minor wound management comes from descriptive studies. Few comparative studies
      examine the effectiveness of topical antisepsis for minor wounds. Several
      clinical trials have demonstrated that tissue adhesives produce short- and long
      term cosmetic results equivalent to those achieved with suture materials. MAIN
      MESSAGE: Sterile saline is the least toxic solution for wound irrigation.
      Chlorhexidine (2%) and povidone iodine (10%) have been the most investigated
      antiseptic solutions. Systemic antibiotics are unnecessary for wounds unlikely to
      be infected. All bite wounds require special attention. Primary closure of bite
      wounds is indicated in certain circumstances: less than 12-hour-old nonpuncture
      wounds, uninfected wounds, and low-risk lesions (such as on the face). In spite
      of their many advantages, skin tapes should be used for low-tension wounds only.
      The popularity of tissue adhesives has greatly increased. Since the advent of
      newer products (with increased bonding strength and flexibility), adhesives are
      used to manage most lacerations except those in areas of high tension (e.g.,
      joints) and on mucosal surfaces. CONCLUSION: Minor wounds not requiring sutures
      can be managed easily in the office.

PMID- 11340759
TI  - Familial ovarian cancer.
AB  - OBJECTIVE: To assist family physicians in evaluating patients' risk for
      hereditary ovarian cancer and to review strategies for preventing ovarian cancer.
      QUALITY OF EVIDENCE: The MEDLINE, EMBASE, CANCERLIT, and CINAHL databases were
      searched from 1970 to 1999 using key words related to hereditary ovarian cancer,
      screening, oral contraceptives, prophylactic oophorectomy, cancer worriers,
      satisfaction, and perceived risk. Recommendations in this paper are based on
      evidence from case-control and cohort studies and, where appropriate, consensus
      conferences. MAIN MESSAGE: Of all women who present with ovarian cancer, 20% have
      a family history of ovarian cancer and 8% carry a BRCA 1 or BRCA 2 mutation.
      Women who carry a BRCA 1 mutation have a 63% lifetime risk of developing ovarian
      cancer, and women who carry a BRCA 2 mutation have a 27% lifetime risk of
      developing ovarian cancer. Preventive strategies include screening (level 3
      evidence for postmenopausal women and level 5 evidence for women with a family
      history of ovarian cancer), use of oral contraceptives (level 3 evidence for the
      general population and for mutation carriers), and prophylactic oophorectomy
      (level 3 evidence in first-degree relatives of patients with breast or ovarian
      cancer). CONCLUSION: Women who have a family history of ovarian cancer should be
      offered genetic counseling and discussion of various preventive strategies for
      minimizing their risk.

PMID- 11340760
TI  - Case report: cutaneous nerve entrapment. Abdominal wall pain in an elderly
      patient.

PMID- 11340761
TI  - 2000 Canadian hypertension recommendations. Summary of recommendations affecting
      family physicians.

PMID- 11340762
TI  - The public awareness of aphasia: an international survey.
AB  - We surveyed 929 shoppers in Exeter (England), Louisiana (USA) and Sydney
      (Australia) to determine what they knew of aphasia. Between 10% and 18% said they
      had heard of aphasia but only between 1.5% and 7.6% had even some basic knowledge
      of aphasia. We found that more females knew something about aphasia than males
      and that older people were more likely to have heard of it, although those with
      some knowledge were significantly younger. Informants had heard of aphasia mainly
      through their work or the media and were mainly professionals like teachers,
      nurses, therapists, managers and administrators, followed by a retired/student
      group. We found some differences in awareness levels in the different locations
      we sampled. Results have implications for targeting awareness raising and
      campaigning.

PMID- 11340763
TI  - Providing intensive therapy in schools for children with no identified provision.
AB  - The provision of a speech and language therapy service to a school-age child with
      little home support and no identified provision for extra help in school has
      always proved challenging to service providers and causes many services to make
      hard choices in terms of best use of limited resources. These children commonly
      at stage three of the Code of Practice (Department for Education 1994) fall
      between two stools: a school which cannot provide extra help in order to carry
      out a speech and language therapy programme; and a speech and language therapy
      service which cannot effect change without back up in the home or school. In this
      paper a project which provides therapy programmes to this group of children via a
      student clinical placements initiative is reported. The project is discussed in
      terms of client outcomes data and offers suggestions as to how findings may be
      interpreted.

PMID- 11340764
TI  - Equity of service: a protocol for management of children with speech problems.
AB  - In an attempt to achieve equity of service, the level of consistency of speech
      and language therapists in making decisions about the management of children with
      phonological delay was examined. Six cases were created and the therapists were
      interviewed about their management and criteria for therapy for each case.
      Decisions were made about standardising practice within the team. A phonological
      care pathway was devised to consider the criteria outlined in the results. This
      pathway is now being piloted with the expectation that it will facilitate an
      equitable service for all children with sound system problems.

PMID- 11340765
TI  - Are we ready to predict speech development from babble in cleft lip and palate
      children?
AB  - The speech development of nine children with cleft lip/palate was followed
      longitudinally from nine months to three years of age. The results indicate
      speech sound development closer to the non-cleft population than previous
      studies. Nasal fricatives previously not extensively described in the literature
      may be an experimental stage of developmental babble, which spontaneously reduce.
      The study has added to the evidence-base for practice in one cleft unit. It may
      be useful to channel resources at our centre to children who at nine months may
      be more at risk, i.e. children with bilateral clefts and known developmental
      delay.

PMID- 11340766
TI  - Measuring language development in deaf children with cochlear implants.
AB  - For the past ten years profoundly deaf children in the UK have been able to
      receive cochlear implants as an alternative to conventional hearing aids. The
      South of England Cochlear Implant Centre (SOECIC) has implanted 78 profoundly
      deaf children. As cochlear implantation is still a relatively new procedure it is
      important to record progress comprehensively. One of the main aims of
      implantation is to give the recipient access to sound so that, in the case of a
      child, they can acquire speech and language. There is a need for a test that
      assesses a wide range of language abilities and which is also sensitive to
      change. The Preschool Language Scales-3 (UK) (PLS-3)(Zimmerman et al. 1997) has
      been standardised on a British population and was chosen to be part of a test
      battery at SOECIC. The test assesses skills from birth to seven years of age and
      has been administered at regular intervals to the clinic population. The outcome
      results show that average scores improve with use following implantation.

PMID- 11340767
TI  - Selective mutism: how a successful speech and language assessment really is
      possible.
AB  - A speech and language assessment of children with selective mutism is often
      difficult because these children are silent in most situations. In Australia, a
      study was designed to assess the children in their homes, the place where they
      usually speak. Five children who met the Diagnostic and Statistical Manual of
      Mental Disorders (American Psychiatric Association 1994) criteria for selective
      mutism participated in the study. Assessment included audio-taping extracts of
      the children's conversations with members of their family and the administration
      of a number of standardised speech and language tests. The study found that four
      of the five children had a communication disorder. This paper outlines these
      communication disorders and describes how a successful speech and language
      assessment of children with selective mutism is possible.

PMID- 11340768
TI  - Treatment of word retrieval in aphasia: generalisation to conversational speech.
AB  - The question of whether treatment gains in picture naming generalise to
      conversation remains relatively unexplored. Several difficulties surround data
      collection and analysis. A quantitative measure of word retrieval in aphasia is
      presented along with relevant details relating to the reliability of the measure,
      and the relationship between word retrieval in picture naming and noun retrieval
      in conversation. We discuss the clinical application of the measure and its
      applicability outside the field of aphasia.

PMID- 11340769
TI  - Mental illness and communication.
AB  - Historical and more recent descriptions of mental illness emphasise the prominent
      nature of communicative difficulties in persons with these diagnoses (Sims 1995)
      and a large part of psychiatric intervention is verbally-mediated. Within this
      study, a theoretically-driven therapy programme addressed the communication needs
      of two persons with schizophrenia. Significant improvements were demonstrated
      using valid and reliable outcome measures.

PMID- 11340770
TI  - Clinical teaching and mentoring: vital in the development of competent
      therapists.
AB  - The needs of under-graduate students and newly qualified speech and language
      therapists (SLTs) are discussed. The results of a small-scale survey of final
      year SLT students and one of newly qualified therapists are presented.
      Similarities between clinical teaching of under-graduates and mentoring of newly
      qualified therapists are identified. The paper calls for a combined training
      course for experienced SLTs to acquire the core knowledge and skills required to
      carry out either or both roles effectively.

PMID- 11340771
TI  - All placements great and small: an analysis of clinical placement offers made by
      SLT services.
AB  - This paper will present the results of a survey of clinical placement offers for
      one academic year in one particular region. The data presented confirm that there
      are issues of shortfall and inconsistency across speech and language therapy
      (SLT) service providers within this region. This information has been analysed in
      a variety of ways and presented to SLT managers within the region and the lead
      NHS Consortium responsible for purchasing SLT education in the context of a 'work
      force cycle'. Suggestions will be made as to possible ways forward using these
      data.

PMID- 11340772
TI  - A strategic approach to clinical placement learning.
AB  - There are different ways of approaching the nationally reported shortages of
      clinical placements for speech and language therapy students in the UK. Viewing
      the problem as a simple issue of high demand and shortfall may result in seeking
      short-term solutions. However, in order to achieve effective longer term change,
      there is a need for an examination of the underlying aspects of the problem. In
      this paper the development and implementation of one department's clinical and
      professional strategy are described and some of the outcomes presented. It is
      suggested that strategic, long-term approaches also need to be considered more
      widely and that a national professional strategy should be developed.

PMID- 11340773
TI  - Student supervision: risky business?
AB  - Radical and rapid reform of the national health service (NHS) has impacted
      significantly on skill-mix and the work organisation of speech and language
      therapists (SLTs) in recent years. These changes impact on student training at
      macro and micro levels. In the context of a society-in-transition, student
      supervision is argued to be a risky business. Six clinicians were selected for in
      depth interviewing, using theoretical sampling procedures. A small-scale
      qualitative enquiry was undertaken to explore the clinicians' perceptions of and
      attitudes towards the risks involved in delegating clinical work to students.
      Thematic analysis of transcribed and coded data was carried out. Risks to
      clients, students and the service are explored from psychological, behavioural,
      medical and structural perspectives. Risk tolerance and risk management
      approaches are described.

PMID- 11340774
TI  - Active learning in service delivery: an approach to initial clinical placements.
AB  - In their first clinical placement and using an active learning approach, students
      provided an extension to existing service provision. Therapist-led teams of six
      students carried out assessment, therapy and advice. Carefully structured
      preparation, supervision and feedback enabled them to discover and develop
      effective approaches for themselves. The learning experience and service
      provision were evaluated and modifications introduced over a three year period.
      Feedback from students and service users confirmed that the project had provided
      both effective learning and a valuable contribution to the local service.

PMID- 11340775
TI  - The gender imbalance among speech and language therapists and students.
AB  - Speech and language therapy is still a predominantly female profession. This
      paper reports the numbers and percentages of males among the population of
      student speech and language therapists in the UK in 1999-2000. The numbers imply
      that there is no prospect of redressing the gender imbalance in the near future.
      Information was gathered by means of a questionnaire to male speech and language
      therapy students and male therapists on the reasons for their career choice and
      their occupation-related experience concerning their gender. Most therapists
      reported advantages from their gender but a minority reported difficulties
      arising from being a man in the speech and language therapy profession. The issue
      of working alone with children is identified as being in urgent need of
      resolution.

PMID- 11340776
TI  - Speech and language functioning in paediatric HIV disease.
AB  - The Human Immunodeficiency Virus (HIV) can potentially cause impairment to
      linguistic functioning. This study was the first to compare selected aspects of
      speech motor control, expressive language and receptive language functioning in
      individual HIV infected children. Results suggested clinically stable HIV
      infected children can develop linguistic impairment. Such impairment is in danger
      of going unnoticed without assessment. Thorough and regular assessment of the
      linguistic functioning of long-term survivors of paediatric HIV disease is
      essential if optimal speech and language therapy management strategies are to be
      devised.

PMID- 11340777
TI  - An alternative management of older children with persisting communication
      problems.
AB  - Speech and language deficits frequently implicate accompanying psychosocial
      problems (such as low self-esteem). An alternative management approach is
      described which adopts a holistic paradigm and provides a unique opportunity for
      intensive work on communication within a supportive environment. The residential
      programme for 8-14 year olds with persistent communication difficulties
      incorporated cognitive, emotional and psychosocial dimensions of communication,
      co-ordinated with work on speech features. Although the programmes were developed
      for children with cleft palate, they have potential for benefiting a wide range
      of communication impairments of different aetiologies. A forthcoming manual with
      resource material developed by the research team will be used in studies across
      these groups.

PMID- 11340778
TI  - Life story books for the elderly mentally ill.
AB  - The use of life story books with people with moderate to severe dementia in
      continuing care and day hospital settings is examined. The approach involved
      activity-based carer and relative training and support. A collaborative approach
      has developed and shifts in staff attitudes are discussed. Consideration is given
      to generalisation to other aspects of patient care.

PMID- 11340779
TI  - A screening instrument for language in older people (Barnes Language Assessment).
AB  - This paper describes the development of a clinically viable tool for the
      assessment of language and associated cognitive skills in the older population
      which was instigated by the SIG Psychiatry of Old Age (South of England). A
      series of sub-tests is described. Data from normal older people is used to
      establish preliminary means and lower normal limits as a guide to distinguishing
      performance associated with normal age-related change from performance associated
      with pathology. The importance of allowing for the effects of normal age-related
      changes on language processing is illustrated. Data from older people with
      pathology attending clinics and hospital departments is also presented.
      Quantitative and qualitative language profiling is outlined. Data analysis
      suggests that the Barnes Language Assessment is able to profile language skills
      and difficulties. Indications for further research are discussed.

PMID- 11340780
TI  - Voice therapy outcomes in vocal fold nodules: a retrospective audit.
AB  - Twenty-six speech and language therapy (SLT) clinical files, in which patients
      presented with a medical diagnosis of bilateral or unilateral vocal fold
      nodule(s), were audited retrospectively over a six year period (1992-1998). The
      objective of the study was to evaluate current practice within our trust in the
      management of patients with vocal fold nodules against what was considered 'best
      practice' and to take action for improvements where deficits were identified.
      Multidimensional outcome measurements were employed. This study lends support to
      experimental findings of treatment effectiveness. Results demonstrated
      elimination and/or reduction of vocal fold nodules in over 70% of clinical files
      audited. Post-therapy over 80% of patients presented with either a normal voice
      quality or a mild degree of dysphonia.

PMID- 11340781
TI  - Speech and language therapists as trainers: enabling care staff working with
      older people.
AB  - A recently completed evaluation of a one day training package on communication
      has found evidence of a perceived need for training in both communication and
      communication impairment among care workers employed by health and social care
      agencies. This paper is a discussion of the factors that contribute to the
      delivery of successful workshops to front line care workers.

PMID- 11340782
TI  - Sharing knowledge with nursing home staff: an objective investigation.
AB  - Nursing home staff are at the forefront of coping with swallowing and
      communication disorders. Our study, which is ongoing, collates information on the
      existing knowledge of such staff and demonstrates how their understanding can be
      increased by speech and language therapists' input. Twenty nursing homes agreed
      to participate in training (91% uptake). To date 16 nursing homes (113 staff)
      have completed training in swallowing and eight nursing homes (47 staff) in
      communication problems. Questionnaires were completed before and after training.
      There was a highly significant improvement after training.

PMID- 11340783
TI  - The communication, speech and gesture of a group of hearing-impaired children.
AB  - The communication skills, speech and gesture of 20 hearing-impaired children were
      assessed. The children were all being educated in a school using an oral/aural
      approach. Assessment result comparison indicated the importance of assessing
      gesture and speech separately for these children and comparing the use of both
      skills. More informal and formal assessment of gesture and the tools to complete
      this task effectively are needed to ensure that these children's communication
      skills are described accurately.

PMID- 11340784
TI  - Listening to deaf speech: does experience count?
AB  - Listening for intelligibility in disordered speech involves a complex interaction
      of factors, including listener experience. This study examines intelligibility as
      perceived by two groups (experienced and inexperienced listeners) in interpreting
      deaf speech. Speech samples were gathered from a hearing-impaired child over
      thirteen months, immediately post cochlear implantation. Results indicate that
      experienced listeners interpret more of disordered speech than inexperienced, but
      while experience appears to be a factor in intelligibility judgements, it does
      not alone guarantee higher intelligibility rating.

PMID- 11340785
TI  - Developing an information pack for the Asian carers of people with autism
      spectrum disorders.
AB  - An investigation is described which forms the basis for the development of an
      information package for the Asian carers of people with autism spectrum disorders
      (ASD) and learning disabilities. The results of semi-structured interviews and
      planning for questionnaires with three different linguistic Asian groups (Urdu,
      Gujarati and Bengali) are presented. The views, attitudes and awareness of
      autism, knowledge of support services and perceived priority of needs are
      analysed for the three different communities. The investigation concludes with
      recommendations as to whether separate information is needed by each culture or
      whether a single information pack can be used and presented in each language
      format. The possible presentation format in which the information can be produced
      is also discussed.

PMID- 11340786
TI  - Evaluating a programme to enhance vocabulary development in pre-schoolers.
AB  - This study was set up to investigate vocabulary development in a population of
      urban Indian socio-economically impoverished pre-schoolers. Since research has
      shown that a correlation exists with vocabulary and reading skills, hence better
      vocabulary would be indicative of fewer reading related problems. The
      introduction of an oracy programme in a nursery was evaluated and the results
      compared with those from a similar nursery not exposed to the programme. There
      was a significant difference in the growth of receptive vocabulary for the
      experimental group relative to the comparison group but no improvement in the
      expressive lexicon of either group. Results shed light on vocabulary development
      and its implications on later literacy progress, as well as changes to nursery
      practice in India.

PMID- 11340787
TI  - The joint delivery of personal and social education (PSE) in a special school.
AB  - There is a growing need for teachers and speech and language therapists (SLTs) to
      work together in the joint planning and implementation of lessons in the
      educational context to ensure successful differentiation of the national
      curriculum (NC) to students with special educational needs (SEN). This paper
      describes and evaluates the development and delivery of a language and social
      communication programme as part of the PSE subject from the NC to final year
      students at a special needs school for children with significant speech, language
      and communication impairment. The topics covered across a variety of common
      social settings are outlined as well as the controlled and progressive manner in
      which they were introduced.

PMID- 11340788
TI  - Language and conversational abilities in Williams syndrome: how good is good?
AB  - Grammatical performance of individuals with Williams syndrome (WS) has been
      reported as being unimpaired, despite their comparatively low IQ and poor general
      cognitive ability. Specific language impairment (SLI) is often seen as the
      converse of WS, showing poor linguistic ability relative to level of cognitive
      functioning. Detailed profiles of language functioning in four children with WS
      and four with SLI are presented which show a much less clear-cut picture than is
      often portrayed and suggest that children with WS may be less linguistically able
      than is commonly reported. A comparison of results on standardised tests with
      performance in real conversations shows that not only the children with SLI but
      also those with WS have significant linguistic difficulties. This has clear
      implications for their management by speech and language therapists.

PMID- 11340789
TI  - Fountaindale Communication Project.
AB  - Voice output communication aids are expensive in terms of initial outlay and
      ongoing staff support. Further efficacy research and innovative methodologies are
      necessary to explore the role of this technology in facilitating communication
      and to develop more informed, effective therapeutic approaches to service
      delivery in this area. A research project is reported that evaluates the progress
      of four children using voice output communication aids. The children's progress
      has been video-recorded at six monthly intervals and analysed using conversation
      analysis and feedback questionnaires. Initial observations and implications for
      service delivery are discussed.

PMID- 11340790
TI  - Comparing language profiles and learning impairment in pupils in special schools.
AB  - Children were selected from schools for pupils with learning difficulties. Non
      verbal ability measures classified them with what was previously termed moderate
      learning difficulties (MLD). A Surrey Speech, Language and Communication Profile
      (Surrey Profile) (Cave and McGregor 1996) was completed for each child and the
      children's cognition scores were compared. Specific language impairment (SLI) was
      determined by the discrepancy between general language functioning and non-verbal
      ability, with a focus on three Surrey Profile items. Three groups were derived
      using a discrepancy model to view the relationship between language and
      cognition. Groups 1 and 2 showed commensurate and mild language difficulties in
      relation to cognition. For Group 3 results indicate that difficulties in learning
      are due to severe and specific language difficulties. Implications emerge for
      assessment, educational placement, provision and intervention.

PMID- 11340791
TI  - Supporting Partners of People with Aphasia in Relationships and Cconversation
      (SPPARC).
AB  - This paper reviews new theoretical and practical developments in working with
      partners of people with aphasia and describes the development of a clinician's
      resource entitled 'SPPARC: Supporting Partners of People with Aphasia in
      Relationships and Conversation'. It focuses particularly on one part of that
      resource: the SPPARC Conversation Training Programme, which adapts conversation
      analysis for clinical use. The paper describes the stages involved in assessing
      and working on conversation in everyday life.

PMID- 11340792
TI  - Sharing learning through narrative communication.
AB  - This paper examines key aspects of the learning experiences of ten speech and
      language therapy (SLT) students on clinical placements, as revealed by an
      analysis of 102 narrative accounts. We argue that when students on placements
      tell stories of their learning experiences the process of recounting them can
      help them to reflect on and consolidate what they have learned and to have this
      learning validated by peer, clinician or tutor audiences. Thus, sharing learning
      through narrative communication is itself further learning from the original
      experience. We show how students evaluate their learning experiences, how their
      growing confidence is mediated by clinicians and how such narratives are shared
      in normal student interaction. Tutors might use the insights from narrative
      learning to raise students' awareness of their own learning, and thus to improve
      it.

PMID- 11340793
TI  - Reviewing the review process: examining decision-making in practice.
AB  - A national multi-disciplinary audit showed variation in SLT practice on the
      decision to review pre-school children or place them on waiting lists following
      initial assessment. Audit evidence suggests some reasons for these differences
      and contributing factors are illustrated by case history examples. Current health
      care policies encourage practitioners to make decision-making transparent to
      consumers but this process is problematic if there is a lack of evidence to
      support principled choice. An outline is presented to enable therapists to gather
      their own evidence for review outcomes in daily practice.

PMID- 11340794
TI  - Evaluation of the Hanen Early Childhood Educators Programme.
AB  - The current study is an evaluation of the Hanen Early Childhood Educators
      Programme (Weitzman 1992). It explores outcomes for both staff and children
      following staff participation in the training programme. Using a comparative
      study design and pre- and post-training measures the changes in staff and
      children were investigated. Results revealed that the training programme did not
      bring about change in children's receptive and expressive language skills.
      Changes were observed in children's social interaction skills. This was
      reinforced by staff reports of changes in children's interaction. Staff changes
      included increased skills and confidence in identifying and supporting children
      with speech and language difficulties alongside positive changes in their
      interaction styles. The methodological difficulties inherent in evaluating
      training effects and the need for further research are highlighted.

PMID- 11340795
TI  - Piloting new ways of working: evaluation of the WILSTAAR Programme.
AB  - The current study aims to investigate the reliability and effectiveness of the
      WILSTAAR screening assessment and intervention programme. It also explores
      parental perceptions and evaluations of their involvement in the intervention
      programme. At this stage data collection is incomplete however interim results
      are presented. False positive rates are slightly higher than expected raising
      questions regarding the screen's reliability. Numbers are too small at present to
      report with confidence on the effectiveness of the intervention programme.
      Results indicate that parents rate their involvement in the WILSTAAR programme in
      a highly positive manner. The need for further research in this area is
      highlighted to ensure that early identification and intervention programmes meet
      the needs of parents and their children.

PMID- 11340796
TI  - Friendship skills in children with specific language impairment.
AB  - An investigation into friendship skills of pre-school children with specific
      language impairment was carried out in both mainstream and specialist play
      settings. Significant differences in onlooker behaviour were found suggesting
      that the children benefited from observation and information-processing time
      within their mainstream play setting. The amount of solitary play behaviour found
      within the specialist setting supported these findings. Conclusions are drawn for
      inclusive education and collaborative practice.

PMID- 11340798
TI  - Drooling in Parkinson's disease: a novel tool for assessment of swallow
      frequency.
AB  - A non-invasive way to obtain objective measurements of swallowing frequency and
      thus indirectly, drooling was required as part of the study 'Drooling in
      Parkinson's disease: objective measurement and response to therapy'. A hard disk,
      digital recorder was developed, for use on a laptop computer, which was capable
      of collecting large quantities of swallowing data from an anticipated 40 patients
      and 10 controls. An electric microphone was taped to the subjects' larynx for
      recording the swallow sounds when drinking 150 ml of water and at rest for 30
      minutes. The software provides an accurate visual display of the audio-signal
      allowing the researcher easy access to any segment of the recording and to mark
      and extract the swallow events, so that swallow frequency may be efficiently and
      accurately ascertained. Preliminary results are presented.

PMID- 11340797
TI  - Drooling in Parkinson's disease: a novel speech and language therapy
      intervention.
AB  - Drooling and difficulty swallowing saliva are commonly reported in people with
      Parkinson's disease (PD). Drooling in PD is the result of swallowing difficulties
      rather than excessive saliva production. Currently, there is little research into
      the effectiveness of treatments to reduce drooling. The aims of the study were to
      develop objective measures of saliva volume and drooling for PD and to assess the
      efficacy of two therapeutic strategies to control drooling, i.e. specific speech
      and language therapy (SLT) including a portable metronome brooch to cue
      swallowing and injections of botulinum toxin into both parotid glands to reduce
      the amount of saliva produced. This paper will describe the assessments used,
      including the measurement of saliva, swallowing and drooling. The main focus will
      be the strategies used in the SLT intervention. The preliminary results are
      presented.

PMID- 11340799
TI  - The efficacy of oro-facial and articulation exercises in dysarthria following
      stroke.
AB  - Although there are many accounts of appropriate oro-facial and articulation
      exercises and treatment hierarchies for clients with dysarthria following stroke,
      there is little evidence relating to the efficacy of such therapy and little or
      no information indicating either the extent or the frequency with which these
      exercises should be practiced for optimum effect. This study investigates the
      efficacy of such traditional therapy for eight clients. A clinic-based therapy
      programme and an exercise routine for home practice was agreed by a group of
      speech and language therapists. The results indicate not only the value of the
      therapy but also a realistic and viable programme for clients to carry out at
      home.

PMID- 11340800
TI  - Transferring skills--from south to north.
AB  - The primary aim of western-trained speech and language therapists (SLTs) working
      in the 'South' is not to train further SLTs but to transfer a range of practical
      skills to carers, health and education workers working directly with under-served
      populations. Considering current areas of service need in the UK, a model of
      primary health care has been applied to the western model, resulting in further
      discussion of potential applications to future SLT practice in the UK.

PMID- 11340801
TI  - Language remediation in mother tongue: a paediatric multilingual picture
      resource.
AB  - Bilingual clients frequently feature on speech and language therapists' caseloads
      and yet they are rarely assessed and treated in their mother tongue. There are
      few assessments targeting languages other than English. Culturally and
      linguistically appropriate assessment and remediation materials should be devised
      for the differing needs of each distinct population. This paper describes the
      Pakistani Heritage Asian population in Rochdale and one of the first steps taken
      to address its needs: the development of an early expressive language assessment
      and remediation package for paediatric clients. Reference is made to the
      importance of identifying the exact languages spoken, especially when the use of
      one language may be perceived as denoting lower social status. Semantic and
      syntactic issues involved in constructing assessments are highlighted.

PMID- 11340802
TI  - The developmental acquisition of English grammar as an additional language.
AB  - The results are presented here of an investigation into the development of
      receptive and expressive English grammar when this is acquired as a second
      language. A cross-sectional survey using standardised assessments was conducted.
      103 children were randomly selected from three local primary schools. These
      children were aged between 5 and 11 years and were acquiring English
      sequentially. Data relating to the receptive and expressive grammar of English as
      a second language was collected from each child. Analysis of this data revealed
      preliminary developmental patterns that appear to be specific to the sequential
      acquisition of English grammar. This data confirms the importance of not using
      data pertaining to the acquisition of first language English for English that is
      acquired as a second language.

PMID- 11340803
TI  - Helping children with communication difficulties in the classroom.
AB  - As we move towards a more inclusive education system teachers are becoming more
      aware of children with speech and language difficulties and the implications for
      their future learning and literacy development. In order to address this and
      promote collaborative working practice between teachers and speech and language
      therapists two advisory speech and language therapy posts were created for a two
      year pilot project.

PMID- 11340804
TI  - Collaborative development of a new course and service in Sri Lanka.
AB  - Great Ormond Street Hospital (GOSH) has a long established service development
      and research programme with Sri Lankan colleagues. The Centre for International
      Child Health (CICH) is an academic unit with public health interests in the
      countries of the South. Together a group of collaborators at GOSH, CICH and in
      Sri Lanka worked together to plan how a cadre of health workers could be prepared
      to work with people with communication disabilities. This is not an uncommon aim
      in under-served countries and there is a small published literature about the
      courses which have been developed. Choices about models for training, service
      delivery and ensuring sustainability in emerging services for people with
      communication disabilities are complex. Links can be made with development work
      in other disciplines. The literature relating to these issues in countries such
      as Sri Lanka is examined.

PMID- 11340805
TI  - Viability and effectiveness of teletherapy for pre-school children with special
      needs.
AB  - Telemedicine is proving valuable in the delivery of health care services. With
      increased competition in telecommunication markets and lower costs, the
      possibility of providing affordable teletherapy services for the 21st century is
      now a goal that can be achieved. Recognition that parent training is a vital
      component of successful treatment programmes makes the use of teletherapy from
      clinic to home an ideal medium of sharing skills with carers. Commercially
      available products were selected on the basis of cost effectiveness, user
      friendliness and audio-visual quality. Parents reported increased knowledge and
      confidence in developing their child's communication skills and teletherapy was
      demonstrated to be an effective, reliable and exciting addition to a new era of
      therapy provision.

PMID- 11340806
TI  - An integrated multi-media package for learning clinical phonetics and
      linguistics.
AB  - Competence in the phonetic and linguistic analysis of normal and disordered
      spoken language is a basic requirement for all students and practitioners of
      speech and language therapy. This paper presents a learning package specifically
      designed for individuals who need to acquire or update practical skills and
      theoretical knowledge in clinical linguistic analysis. VISUAL-CLIP (VIdeo
      SUpported Active Learning in Clinical LInguistics and Phonetics) is a student
      centred, interactive, multi-media tutorial in clinical linguistics and phonetics,
      based on digitised video- and audio-taped speech data from a child with a complex
      communication disorder. Data can be analysed from different perspectives and at
      different levels of difficulty using separate but inter-linked modules on
      phonetics, phonology, grammar, semantics and pragmatics. Case history
      information, formal assessment results, theoretical background and an annotated
      bibliography are also integrated into the CD-ROM based package.

PMID- 11340807
TI  - Students' expectations of learning key skills and knowledge.
AB  - Students' expectations of the key skills and knowledge they acquire and how their
      perceptions of these change during the four year period of their speech and
      language therapy (SLT) degree programme are explored. This is important because
      students are central to the teaching and learning process so their expectations
      of learning have to be taken into account in order to best help them to achieve
      the required learning outcomes. Over 100 De Montfort University (DMU) SLT under
      graduate students from the four years were surveyed by questionnaire. The
      research findings are discussed to examine the significance of differences
      between and within year cohorts. The outcomes of this research will provide a
      basis for recommendations for DMU and other universities' SLT programmes, and for
      the improvement of student learning guidance.

PMID- 11340808
TI  - The UK education of overseas students in speech and language therapy.
AB  - Informal evidence suggests that many overseas speech and language therapists
      (SLTs) either do not return to their home country on qualification or do not work
      as SLTs in the public sector. Many factors may contribute to this situation.
      However, concern that it may result in part from a poor match between UK SLT
      education and the demands of the role in other countries, led the Royal College
      of Speech and Language Therapists (RCSLT) to fund a study of overseas SLT
      students' experiences of UK qualifying courses. The study involved questionnaires
      and interviews with current students and those qualifying since May 1994. The
      focus of this paper is the respondents' experiences of studying and working in
      the UK, their views of the advantages and disadvantages of working in their home
      countries and the UK and supportive strategies that UK universities and other
      agencies might adopt. Implications of the findings are discussed.

PMID- 11340809
TI  - Meta-syntactic therapy using visual coding for children with severe persistent
      SLI.
AB  - The results of a pilot study into meta-syntactic therapy using visual coding for
      four children (age 11-13 years) with severe receptive and expressive specific
      language impairment (SLI) are presented. The coding system uses shapes, colours
      and a system of arrows to teach grammatical rules. A time-series design
      established baseline pre-therapy measures of comprehension and production of both
      passives and 'wh' questions. All participants made progress with passives and
      this was significant in three cases of the four. Comprehension and production of
      'wh' questions also improved in all participants, although this did not always
      reach statistical significance. The results indicate that meta-syntactic therapy
      of grammatical rules, capitalizing on visual strengths, can improve both
      comprehension and production in secondary age children with severe persistent
      SLI.

PMID- 11340810
TI  - Gesture use following right hemisphere brain damage.
AB  - A group of eight right hemisphere brain damaged (RHBD) individuals' use of
      gesture during discourse was explored at two points post stroke. Three topic
      structured conversational and three procedural discourse samples were elicited at
      one and six months post stroke. Gestures were analysed in terms of communicative
      gesture use and use of physical movements. Results suggest the group's use of
      gesture altered little over time. Some indication of change in the use of head
      movements and the use of kinetographic gestures were suggested as aspects of
      gesture use following RHBD that would benefit from further investigation in
      relation to a non-brain damaged (NBD) control group.

PMID- 11340811
TI  - 'Do you speak practice-ese?' A discourse of practice for sharing communication.
AB  - Speech and language therapy (SLT) is absorbed in an empirical (or 'scientific')
      discourse. A case study, involving a single practitioner, is reported. SLT's
      application of an empirical discourse is critically investigated. Results reveal
      that SLT engages reductionism, essentialism, and 'dis-othering' in its practice
      discourse. Consequently, rich, textured lives are re-manufactured in a less than
      authentic manner. A critically oriented practice discourse is recommended to
      assist SLT in reconsidering its present immersion in a reductionistic, technical
      and utilitarian discourse and toward a discourse that assists an effective
      sharing of communication.

PMID- 11340813
TI  - Safe swallowing?--an opportunity for students working with dysphagic clients.
AB  - The challenges of providing student speech and language therapists (SLTs) with
      clinical experience in acute hospital settings are outlined. An innovative model
      of student clinical placement will be described which takes advantage of the
      recent change in policy by the Royal College of Speech and Language Therapists
      (RCSLT) in respect of student involvement in work with dysphagic clients.

PMID- 11340812
TI  - An inter-disciplinary approach to swallowing problems in acute stroke.
AB  - Many speech and language therapy (SLT) departments are in danger of being swamped
      with dysphagia referrals, often to the detriment of other work. At the same time
      surveys have shown that large numbers of patients with acute stroke have
      swallowing problems which are poorly managed during the critical early phase, not
      referred or missed altogether. The Collaborative Dysphagia Audit (CODA) study,
      carried out in six British hospitals, showed that nurses could quickly be trained
      to carry out basic screening assessments for dysphagia and that implementation of
      a co-ordinated inter-disciplinary dysphagia management policy (DMP) could
      substantially improve the proportion of dysphagic patients in whom appropriate
      feeding precautions were taken. These early DMPs were limited by the need for
      ward staff to keep all patients with suspected swallowing impairment nil by mouth
      until assessed by SLT, so in some acute stroke units nurses have been trained to
      a higher level which allows them to manage most routine transient swallowing
      problems, leaving only complex or persistent cases for referral to SLT. This
      approach has been used successfully in our unit in Gateshead, where a dysphagia
      nurse specialist post has been set up to act as a link between ward staff and
      SLTs, to ensure that the necessary training levels are maintained and to co
      ordinate the DMP.

PMID- 11340814
TI  - A collaborative approach to the assessment and management of dysphagia.
AB  - An inter-disciplinary approach to the assessment and management of dysphagia is
      essential. A partnership between speech and language therapists (SLT) and nurses
      combines in-depth experience of dysphagia with the holistic knowledge of the
      patient. Nurses in acute, rehabilitation and mental health settings are trained
      by SLTs to use a locally-developed screening tool. This allows the nurse to carry
      out a basic screening assessment when dysphagia is identified, start an interim
      feeding regime and monitor the patient's progress. Simple or short-term dysphagia
      can be managed by the dysphagia trained nurses (DTNs). Experience, qualitative
      and quantitative measurement has shown benefits. Audit results enable us to share
      our experiences and to plan for future development of the project including a
      formal validation of the tool.

PMID- 11340815
TI  - Dysphagia training for nurses in an acute hospital setting--a pragmatic approach.
AB  - Dysphagia assessment and management has significant impact on speech and language
      therapy (SLT) resources. Recent reports have highlighted nurses' role in the
      nutrition of their patients. In order to focus SLT input efficiently and
      effectively and to improve nurse confidence in management of patients with
      swallowing problems, a dysphagia screening test (DST) was devised for use by
      nurses within an acute teaching hospital setting. This has since been used for
      training SLT students and junior doctors.

PMID- 11340816
TI  - Dysphagia training programmes: 'fixes that fail' or effective inter-disciplinary
      working?
AB  - A number of factors influencing the development of dysphagia training programmes
      are identified, some of which relate to cultural issues and to the way systems
      operate. Lessons can be learned from current theories of relevance to effecting
      change in professionals' working practice. These lessons can be applied beyond
      dysphagia to other areas in which speech and language therapists are involved.

PMID- 11340817
TI  - Benchmarking can facilitate the sharing of information on outcomes of care.
AB  - Recent restructuring in the national health service (NHS) aimed to effect
      cultural and organisation changes that would ensure fair and equal access for
      service users to effective and efficient services. Clinical governance has been
      introduced as a means of delivering quality improvement. One element of this is
      the use of benchmarking to assess current process and outcome and to use
      comparative information to inform about current and best practice. The use of the
      Therapy Outcome Measure (TOM) (Enderby and John 1997) was investigated as an
      indicator to benchmark the outcomes of treatment for different client-groups and
      compare patterns of outcomes from different speech and language therapy (SLT)
      services. The study recruited eight SLT trust sites and ran for eighteen months.
      The TOM data was analysed to note similarities and differences in cases entering
      treatment, in the direction of change resulting from treatment, and on completing
      treatment. Variation was found on these points between cases with different
      disorders and across the trusts. TOM data could be used to provide a benchmark
      for a disorder against which services could make comparisons. However, for
      benchmarking to succeed there is a need for support and commitment from every
      level of an organisation.

PMID- 11340818
TI  - Implementing the picture exchange communication system (PECS).
AB  - PECS was developed in Delaware, USA over 10 years ago by Bondy and Frost (1994a).
      Over the last two years PECS has been introduced to this country and has raised a
      great deal of interest in people working in the field of autistic spectrum
      disorders (ASD). This paper will address some of the issues that arose during the
      establishment of PECS in one special school. Changes seen in 21 children with
      severe learning difficulties who have been taught to use PECS are reported and
      the use of PECS with children who do not have an ASD is discussed.

PMID- 11340819
TI  - The application of student-centred learning approaches to clinical education.
AB  - This paper explores current thinking on adult learning and discusses its
      application to the clinical education of speech and language therapy students. It
      is based on evidence from a two-year project funded by the Trent Regional
      Consortium, which is trialling an innovative means of providing paediatric
      placements. The educational literature has recognised for some time the
      importance of student-centred teaching and learning and has encouraged movement
      away from a didactic teacher-student model to one where students are seen as
      active in the learning process. This paper offers a model as to how these
      principles may be applied to clinical placements to promote self-directed
      lifelong learning and to prepare speech and language therapists to meet the
      challenges of continuing professional development and the ever-changing working
      environment.

PMID- 11340820
TI  - The development of a self-directed and peer-based clinical training programme.
AB  - A reflective learning approach for clinical training with final year students is
      described. The training programme aims to promote the development of independent
      and reflective practitioners. The theories and ideas that have influenced the
      structure of the programme are described and an outline of the programme is
      provided. The views of students who have participated in the process are
      discussed. Most students were positive about their experiences, but some problems
      were reported. Suggestions for improving the supervisory process are considered.

PMID- 11340821
TI  - Informing educational change to improve clinical competence.
AB  - The factors that have influenced the current approaches to speech and language
      therapy education in Great Britain are discussed. A project is presented which
      will provide data on how educational approaches can more clearly reflect
      professional practice.

PMID- 11340822
TI  - Profiling the membership of self-help groups for aphasic people.
AB  - We surveyed the membership of aphasia self-help groups in England. We wanted to
      know what kinds of people become members and the factors associated with taking
      an active role. So we aimed to describe the membership in terms of age, aphasia
      severity, physical state, socio-economic status and group roles. We collected
      data on 135 members and found them relatively less severe but mainly chronically
      aphasic, living in their own homes and close to the group meeting place, using
      their own or public transport, with little community or state aid. While
      hemiplegia was common, few were wheelchair bound. Those taking active roles were
      younger and less severely aphasic and from more professional and managerial socio
      economic groups.

PMID- 11340823
TI  - Reflective logs: an aid to clinical teaching and learning.
AB  - This paper reports on the use of learning logs for clinical teaching and learning
      in a university clinic. Students were encouraged to submit a written summary of
      their reflections after each clinical session for discussion at the subsequent
      session. Evaluation has shown that clinician-teachers and students value this
      approach because it facilitates clear goal-setting, promotes information exchange
      and provides opportunities for explicit focus on the student's learning needs.
      Although most students reported that completion of the learning log is time
      consuming, the majority considered that this was balanced by the benefits,
      including opportunities for additional feedback and the 'licence to ask
      questions'. The evaluation has also shown, however, that few students elected to
      use their learning logs in subsequent placements, particularly when these were
      undertaken away from the university clinic. Some possible reasons for this are
      explored.

PMID- 11340824
TI  - Teacher/therapist collaboration: a Scottish higher education institution
      development.
AB  - The collaborative work is described of a principal speech and language therapist
      (SLT) and a lecturer in a college of education in Scotland in writing and
      evaluating a Post Graduate Award Scheme (PGAS) module. This was in response to
      Her Majesty's Inspectorate's (HMI) (1996) recommendation that teacher education
      institutions should 'consider the in-service and post-graduate training needs of
      those working with pupils with language and communication disorders and autism'.
      Official Scottish Executive Education Department (SEED) statements were examined
      by analysing HMI (1996) and subsequent official documents. Higher educational
      (HE) institution statements were read in the PGAS handbook and in the module
      descriptor (Northern College 1998). Accounts of change are described in the
      thinking and practice of course members as a result of the module and the
      implications for future module development are considered.

PMID- 11340825
TI  - Supporting primary and secondary pupils with communication and behaviour
      problems.
AB  - Numerous studies have identified communication skills as being most predictive of
      long-term school success. A Communication Opportunity Group Scheme (COGS) took
      place in a primary and secondary school involving 36 students aged 7-15 years.
      There were 24 subjects in two types of teaching group and 12 controls. One group
      was taught for an hour a week over ten weeks (weekly) and the other for two hours
      daily over five days (intensive) by teachers trained in the COGS method.
      Experimental groups showed significant gains compared with controls. Integrating
      systematic teaching of communication into the curriculum may significantly
      increase pupil performance. The project has fostered a learning community of
      schools, support services, national charities and the university.

PMID- 11340826
TI  - The Listening Skills Test--a new instrument to assess children's pragmatic
      ability.
AB  - Research has established that the development of autonomous (as opposed to
      collaborative) communication skills, using referential communication speaker and
      listener tasks, develops only slowly during the primary school years. Such a
      finding has implications for the classroom which puts a premium on independent
      language processing. Although the importance of oral language is recognised in
      the National Curriculum, there has been little attempt to assess the ability
      formally. The Listening Skills Test is a standardised pragmatic instrument
      focusing on the 3 1/2-7 years age group. The test is in four parts and assesses
      the ability to make judgements about the efficacy of verbal messages or
      instructions. Tasks include relating messages to arrays of pictorial items,
      making judgements about statements that refer to one complex picture, marking
      routes on a street plan in response to an extended set of instructions, and the
      ability to evaluate purely verbal utterances. The overall aim of the test is to
      assess children's ability to make sense on their own of verbal information in a
      decontextualised situation thought to represent the nature of much transactional
      communication in the classroom. Suggestions for remediation that have arisen from
      research conducted by the authors are also discussed.

PMID- 11340827
TI  - Day in, day out: the everyday therapy of community clinics.
AB  - This paper describes the timing and nature of therapy provided within a recent
      randomised controlled trial (RCT) of preschool speech and language therapy
      services. There is literature that describes and evaluates speech and language
      therapy but there is little indication of how this is translated into everyday
      practice. The study collected data from 21 speech and language therapists (SLTs)
      in 16 community clinics. The areas targeted, goals, approaches used, the
      frequency and timing of contact for the 68 children who received treatment were
      documented. The data show that several aspects of therapy were frequently
      targeted simultaneously, that approaches were combined and that the frequency of
      therapy did not vary with severity. The discussion will consider the gap between
      published programmes and everyday practice and the implications for
      effectiveness.

PMID- 11340828
TI  - Investigation of theoretical models and therapy activities: phonological
      difficulties.
AB  - A focus group of seven speech and language therapists (SLTs) who work with
      children with phonological difficulties was invited to share their views on their
      current ways of working. Qualitative data was generated through discussion of two
      video-taped recordings of children with phonological difficulties and a series of
      brainstorming tasks. The results indicate the use of an electric approach, a
      mixture of theories rather than a single one. Similarities and differences
      between SLTs are identified. Implications for the development of clinical
      guidelines and the investigation of effectiveness are discussed.

PMID- 11340829
TI  - Mainstream paediatric speech and language therapy service population:
      epidemiology.
AB  - The epidemiology of 1090 referrals to a mainstream paediatric speech and language
      therapy department over fifteen months is discussed, in relation to referral
      information and initial detailed assessment. Clients are classified by their main
      presenting difficulty and by their degree of severity. This information will
      inform clinicians of the nature of the caseload of a typical inner city service
      which will, in turn, aid service planning.

PMID- 11340830
TI  - Seeing the person? Disability theories and speech and language therapy.
AB  - The potential value of a framework enabling practitioners to conceptualise speech
      and language therapy from a range of perspectives engendered by different
      theories about disability is explored. Four disability research paradigms are
      used to categorise professional activities, whilst the 'individual' and 'social'
      models of disability are considered as alternative value systems. Challenges
      facing speech and language therapists in developing roles and services to embrace
      different perspectives are outlined.

PMID- 11340831
TI  - Users in the driving seat or sitting alongside map-reading?
AB  - The government agenda is clear. At the highest level users are involved in policy
      making. We as service providers need to show evidence that users views are
      elicited and used to improve the quality of care. The tool bag of techniques used
      to elicit users views will be explored--questionnaires, structured interviews,
      focus groups and innovative cognitive techniques such as perception score cards.
      We explore the continuum of user-led qualitative techniques to provider-led
      quantitative approaches. Building a framework of techniques which cover the
      diverse needs of people using a speech and language therapy (SLT) service is a
      challenge. A greater challenge is using the views of users to bring about
      meaningful change.

PMID- 11340832
TI  - Speech and language therapy for adults in Hackney: an assessment of need.
AB  - With the development of separate community and the hospital trusts in the London
      borough of Hackney, at a time of increasing numbers and range of referrals, a
      number of gaps in service became apparent. The need for community adult speech
      and language therapy (SLT) in Hackney was identified, based on previous studies
      and other relevant literature. Comparison with services locally and nationally
      shows clearly that Hackney, in having virtually no community SLT for adults, is
      significantly disadvantaged. It was intended that this work would result in the
      widest consultation and discussion by the relevant agencies to explore ways of
      meeting this need.

PMID- 11340833
TI  - Multi-professional staff development programme for PAMs.
AB  - A unique, accredited, multi-professional education programme for junior staff in
      professions allied to medicine (PAMs) developed by Durham and Teesside Education
      and Training Consortium in collaboration with local trusts and social services is
      described. Designed to ensure competence to practice in line with clinical
      governance, it aims to strengthen multi-professional working practice through a
      greater understanding of roles and of the way the national health service (NHS)
      works. It enables staff to analyse their own learning needs and to employ self
      directed learning skills for life-long learning. Using problem-based learning, it
      uses real clinical cases as triggers to promote critical evaluation and reasoning
      and the development of multi-professional care pathways.

PMID- 11340834
TI  - Child'sTalk--for children with autism and pervasive developmental disorder.
AB  - A research assessment protocol and early intervention approach designed for use
      by multi-disciplinary professionals with children who have the severe social
      communication deficits of early autism and pervasive developmental disorder (PDD)
      are described. The assessment analyses the specific pattern of social
      communication impairment in each child and defines the characteristics of the
      dyadic communication between parent and child. The intervention aims to identify
      facilitative strategies, using video feedback, which lead to close interpersonal
      interaction between the child and their parents. Parents can reflect on their own
      interaction and identify which strategies successfully engage their child.
      Child'sTalk aims to facilitate adaptations to the child's level of communication
      by sensitively and finely tuning the interaction and mutual sharing of intentions
      as a fundamental agent for the emergence of communication.

PMID- 11340835
TI  - Making it to work: towards employment for the young adult with autism.
AB  - In the last few decades there has been an increase in the reported prevalence of
      autism and its correlates within what is now termed autistic spectrum disorder
      (ASD): from 20 in every 10,000 children being estimated by Wing and Gould (1979)
      to 91 in every 10,000 by the National Autistic Society (NAS) (1999). While
      changes in criteria may account for some of this it is accepted that such
      children are increasingly being identified and knowledge of autism is growing.
      Semi-structured interviews were conducted with nine teaching staff from seven
      different schools for children with special needs to elicit information in
      relation to preparing young adults with ASD for the world of work. Results
      indicated educational practices are being modified for children with autism.
      Currently the most specifically tailored packages are offered in schools for
      children with severe learning difficulties.

PMID- 11340836
TI  - Challenges and opportunities for speech and language therapists in secondary
      schools.
AB  - Language and communication difficulties experienced by secondary school students
      are outlined. The challenges that the secondary school environment presents for
      both children and speech and language therapy services are discussed. Two case
      studies illustrate how speech and language therapists (SLTs) working for the
      Newham Education Authority Language and Communication Support Service support
      students in their secondary schools.

PMID- 11340837
TI  - Software and speech--a review of software in phonology therapy.
AB  - A review of software was carried out to evaluate to what extent particular titles
      could be used within a phonological therapy programme using a psycholinguistic
      approach for children aged between four and seven years. Some of the software had
      been developed specifically for speech and language therapists working with
      children's phonological impairments. Other titles were from the education market
      and aimed at developing children's literacy skills. This paper describes how
      these software programmes could be used to address phonological impairments
      through developing the sub-skills described within the psycholinguistic
      framework.

PMID- 11340838
TI  - Screening for speech and language impairment: a follow-up of true negatives and
      false positives.
AB  - It is important to ascertain the validity of screening and case-finding
      procedures in terms of long-term outcome, particularly if they constitute the
      primary mode of accessing services. This study is a follow-up of a group of True
      Negatives and False Positives from the 'original' study (Laing et al. 2000),
      which investigated the concurrent validity of a parent-led method and a formal
      screening method. Nine (29.03%) of the 31 children who were re-assessed fell
      below the cut-off point for referral and were identified as cases. In particular,
      as many as eight (57.14%) of the 14 false positives were referred.

PMID- 11340839
TI  - Who's afraid of the randomised controlled trial? Parents' views of an SLT
      research study.
AB  - Evidence-based health care is now a reality within the national health service
      (NHS) and the randomised controlled trial (RCT) is the linchpin of this movement.
      In modern health care, there has also been a shift towards understanding client
      perspectives. With regard to clients' participation in research, much
      consideration has been given to ethical issues and barriers to participation.
      However, less attention has been paid to the participants' views of clinical
      trials and understanding how they construe the research. This paper reports a
      study of the attitudes of parents whose children took part in an RCT. Data were
      collected from the parents of 20 children, using qualitative in-depth interviews.
      Parents talked about the meaning of their participation, their motivation for
      taking part and their understanding of the nature of the trial. The implications
      of the findings for future research will be considered.

PMID- 11340840
TI  - An audit of the application of care aims across the south west Thames region.
AB  - Care aims are a means of defining the purpose of intervention of health care. The
      Malcomess care aims model uses these labels to guide the planning, delivery and
      outcome measurement of care. Within speech and language therapy (SLT) this
      involves the use of one of seven labels which clarify and make explicit the
      purpose of each episode of care undertaken with a client. This relatively simple
      application has been shown to change the way SLTs work, clarifying expectations
      of many who use the service. In the South West Thames Region, a project was put
      in place for SLTs which included undertaking training, audit and support. The
      outcome of the audit showed that care aims had been adopted across the region in
      a sufficiently flexible way to meet local needs and offered therapists the tools
      to reflect on the types of interventions provided to clients.

PMID- 11340841
TI  - The Hanen Parent Programme: a parent's perspective.
AB  - In 1997 Salford Community Healthcare Trust embarked on a research project (funded
      by NHS Executive North West Region) to investigate how viable the Hanen Parent
      Programme (HPP) (Manolson 1992) was in terms of its effectiveness and suitability
      for an inner-city UK population in comparison with clinic-based, direct
      intervention. An important component of that research project involved exploring
      the parents' perceptions of the therapy they had undertaken. In this paper are
      summarised the areas in which there were marked differences between parents'
      experiences and perceptions of therapy as a result of the type of intervention
      they received. Clinical implications are discussed.

PMID- 11340842
TI  - Evaluating training courses for parents of children with cochlear implants.
AB  - The purpose of this study was to investigate the change in effective
      communication between parents and children with cochlear implants when the
      parents attended a modified Hanen training course (Watson 1995). The study
      demonstrates that the course led to improvement in the effectiveness of the
      parent-child interaction, as rated by naive independent observers. The Erber
      rating scale (Erber et al. 1995) was implemented as a tool for evaluating changes
      before and after the courses. Using video samples taken at the above intervals,
      the ratings showed a significant increase in effective communication at the end
      of the courses.

PMID- 11340843
TI  - Sharing stories: life history narratives in stuttering research.
AB  - The life experiences of people who stutter (PWS) have not featured prominently in
      research. Historically, the profession of speech and language therapy has amassed
      data and developed its theory of stuttering within a positivistic frame. As a
      consequence, the existing over-arching theory of research and practice does not
      engage holistically with the dynamic personal, socio-cultural and political
      contexts of the individual who stutters. Therefore a conceptual shift is required
      in ontology, epistemology and methodology underpinning the knowledge construction
      process. The use of the life history narratives as a research tool is promoted.
      An exploratory study of a single participant is presented to illuminate the
      methodological approach and emerging theoretical constructs.

PMID- 11340844
TI  - 'Insuring' a correct differential diagnosis--a 'forensic' collaborative
      experience.
AB  - Mr. J was referred to a speech and language therapist (SLT) by a consultant
      psychiatrist. He had sustained an industrial accident which he claimed was
      responsible for a range of problems which included a speech and language problem.
      Some three years after his accident, he brought an action for damages arising out
      of the accident. His solicitor, on the recommendation of the consultant
      psychiatrist, contacted the SLT requesting his views as to whether Mr. J's speech
      difficulties were due to the injuries sustained and requesting recommendations
      for further treatment. The SLT saw Mr. J and concluded that he had problems at
      all communication levels, the greatest being an articulatory impairment. Some
      reports suggested a psychological basis for his problems and others, including
      the psychiatrists', suggested an organic basis.

PMID- 11340845
TI  - A survey to identify therapists' high-tech AAC knowledge, application and
      training.
AB  - Recent research in Australia (Balandin and Iacono 1998) has identified a lack of
      postgraduate training in high tech or electronic alternative and augmentative
      communication (AAC) equipment for speech and language therapists (SLTs). At
      Treloar College (TC) the SLTs have acquired wide experience and knowledge that
      could be shared with others who have fewer clinical opportunities to acquire
      skill in this area of expertise. Questionnaires were sent to 500 SLTs selected at
      random. The purpose of the questionnaire was to identify how knowledgeable SLTs
      in various clinical settings across the UK considered themselves to be in the
      prescription, training, support and use of high tech AAC in an increasingly
      technological world.

PMID- 11340846
TI  - Phonological and orthographic approaches to the treatment of word retrieval in
      aphasia.
AB  - We present a preliminary report on a study of the treatment of word finding
      difficulties in aphasia using phonological and orthographic cues. These
      techniques although often used to cue word finding in the immediate term have
      been little evaluated in terms of therapy designed to improve word retrieval in
      the long term. The first phase using cued word retrieval in a picture naming task
      was followed by a second phase designed to facilitate use of treated words in
      real-life contexts. The results from both phases were encouraging with improved
      word retrieval for three out of the four participants. The implications for
      clinical practice are discussed.

PMID- 11340847
TI  - Supporting parents of children with communication difficulties: a model.
AB  - The project focuses on 'shared listening' from a structured developmental
      framework of 'sound/no sound awareness' to basic 'phonological awareness' linking
      it to the Foundation Curriculum: Early Years Goals (Department for Education and
      Employment 2000) and National Literacy Framework (Department for Education and
      Employment 1998). The project is based around parents borrowing topic bags where
      their children have been identified by speech and language therapy/specialist
      language and communication support teachers as having listening/phonological
      difficulties. Following a simple screening assessment parents borrow the bags
      weekly for a potential 30 weeks. These have been shown to have an effect on both
      parental attitudes to helping listening (practically-based and focused) and their
      children's listening skills.

PMID- 11340848
TI  - Early screening for dyslexia--a collaborative pilot project.
AB  - An ongoing collaborative project, currently being piloted in 12 Wiltshire primary
      schools, is described. The aim is to provide a means of identifying potentially
      dyslexic children by the end of Key Stage 1 (Year 2) with a view to early
      intervention. The causal links identified by research between phonological skills
      and literacy development are taken as the theoretical basis of an initial
      screening procedure, and an intervention package is implemented for identified
      children. Those demonstrating persistent difficulties one year later are further
      assessed over a school term using an assessment package designed to identify
      those children showing a dyslexic profile. Further intervention is then planned
      and implemented.

PMID- 11340849
TI  - Experiences of ending aphasia therapy.
AB  - Despite a considerable literature on assessment and treatment issues in
      aphasiology, little has been written about how therapy ends. We lack detail about
      how clinicians decide to terminate treatment and about how patients and carers
      view leaving therapy. This paper explores experiences and perceptions of aphasia
      treatment termination. It uses in-depth interview data gathered in South
      Australia as part of a doctoral study with a speech pathologist, three ex
      patients with aphasia and one spouse. This case study allows comparison of client
      and professional narratives to each other and also to the official discharge
      documentation in the medical file. The discharge process arising from this
      analysis is discussed.

PMID- 11340850
TI  - Measuring quality of life in people with aphasia: the Stroke Specific Quality of
      Life Scale.
AB  - Assessing health related quality of life (HRQOL) in people with communication
      disabilities is a challenge in health related research. Materials used to assess
      HRQOL are often linguistically complex and their mode of administration usually
      does not facilitate people with communication disabilities to give their
      experiences. We are currently running a medium scale study (80 participants)
      which aims to explore the HRQOL of people with long-term aphasia and to assess
      the psychometric properties and the acceptability of the Stroke Specific Quality
      of Life Scale (SS-QOL) (Williams et al. 1999) as a single measure for the
      assessment of HRQOL in this population. Here the initial stages of modifying the
      SS-QOL for use with people with aphasia will be presented. We will concentrate on
      the process of making the scale communicatively accessible to people with aphasia
      and increasing its content validity with this population group.

PMID- 11340851
TI  - Evaluation of a model of intervention to create a visually enriched environment.
AB  - Within a day resource for people with learning disabilities 'stand-alone' signing
      training proved ineffectual to sustain lasting change in the formalised gestural
      behaviours of carers. Consideration was given to setting conditions pre- and post
      training and a new model of delivery evolved, designed in partnership with day
      resource staff. Aims of intervention were to promote the adoption and active use
      of signing as an aid to communication and move towards a partnership framework
      which values the role of carers as co-facilitators and lessens dependency on the
      therapist. This paper describes and evaluates a training model which was found to
      be successful in translating knowledge into changes in practice and discusses the
      critical factors which should be built into future interventions.

PMID- 11340852
TI  - Can't or won't? Evidence relating to authorship in facilitated communication.
AB  - Most experimental evaluations of Facilitated Communication (FC) provide no
      evidence that this technique is valid. Important as they are, controlled test
      based studies have characteristically not done justice to the complexity of the
      issues which surround FC. This paper summarises a long term evaluation project
      involving various forms of data collection. In this study too, controlled testing
      has shown very little evidence for the validity of the technique. In contrast,
      other sources of data, including records of naturally occurring message passing
      and intensive video analysis have provided evidence that the communication skills
      of some FC users have been enhanced. An overview of the project is presented, and
      discussed in relation to the blurring of findings (observations of behaviour) and
      inferences (judgements of communicative competence) in the extant literature.

PMID- 11340853
TI  - Bayes factor of model selection validates FLMP.
AB  - The fuzzy logical model of perception (FLMP; Massaro, 1998) has been extremely
      successful at describing performance across a wide range of ecological domains as
      well as for a broad spectrum of individuals. An important issue is whether this
      descriptive ability is theoretically informative or whether it simply reflects
      the model's ability to describe a wider range of possible outcomes. Previous
      tests and contrasts of this model with others have been adjudicated on the basis
      of both a root mean square deviation (RMSD) for goodness-of-fit and an observed
      RMSD relative to a benchmark RMSD if the model was indeed correct. We extend the
      model evaluation by another technique called Bayes factor (Kass & Raftery, 1995;
      Myung & Pitt, 1997). The FLMP maintains its significant descriptive advantage
      with this new criterion. In a series of simulations, the RMSD also accurately
      recovers the correct model under actual experimental conditions. When additional
      variability was added to the results, the models continued to be recoverable. In
      addition to its descriptive accuracy, RMSD should not be ignored in model testing
      because it can be justified theoretically and provides a direct and meaningful
      index of goodness-of-fit. We also make the case for the necessity of free
      parameters in model testing. Finally, using Newton's law of universal gravitation
      as an analogy, we argue that it might not be valid to expect a model's fit to be
      invariant across the whole range of possible parameter values for the model. We
      advocate that model selection should be analogous to perceptual judgment, which
      is characterized by the optimal use of multiple sources of information (e.g., the
      FLMP). Conclusions about models should be based on several selection criteria.

PMID- 11340854
TI  - Orthographically mediated inhibition effects: evidence of activational feedback
      during visual word recognition.
AB  - Models of visual word recognition that have adopted an interactive activation
      framework (e.g., Coltheart, Curtis, Atkins, & Haller, 1993; Grainger & Jacobs,
      1996) assume that activation can spread from semantic to orthographic
      representations via a feedback mechanism during visual word recognition. The
      present study used a mediated priming paradigm to test whether such feedback
      exists and, if so, under what conditions. Participants named aloud targets that
      were preceded either by a semantically related prime (e.g., dog-cat) or by a
      prime that was related to the target via a mediating word (e.g., cat-[dog]-bog).
      Direct evidence of activational feedback was obtained in the form of
      orthographically mediated inhibition effects. These mediated inhibition effects
      are consistent with activational feedback and support models of visual word
      recognition that have adopted an interactive activation framework.

PMID- 11340855
TI  - Modulating semantic feedback in visual word recognition.
AB  - According to the interactive activation framework proposed by McClelland and
      Rumelhart (1981), activation spreads both forward and backward between some
      levels of representation during visual word recognition. An important boundary
      condition, however, is that the spread of activation from lower to higher levels
      can be prevented (e.g., explicit letter processing during prime processing
      eliminates the well-documented semantic priming effect). Can the spread of
      activation from higher to lower levels also be prevented? This question was
      addressed with a choice task procedure in which subjects read a prime word and
      then responded to a target, performing either lexical decision or letter search
      depending on the color of the target. A semantic context effect was observed in
      lexical decision, providing evidence of semantic-level activation. In contrast,
      there was no semantic context effect in the letter search task, despite evidence
      of lexical involvement: Words were searched faster than nonwords. Further
      evidence of lexical involvement in the letter search task appeared in Experiment
      2 in the form of greater identity priming for words than for nonwords. The
      results of these experiments are consistent with the conclusion that feedback
      from the semantic level to the lexical level can be blocked. Hence, between-level
      activation blocks can be instantiated in both bottom-up and top-down directions.

PMID- 11340856
TI  - Illusory words created by repetition blindness: a technique for probing
      sublexical representations.
AB  - When two orthographically similar words are displayed using rapid serial visual
      presentation (RSVP), the repeated letters in the second critical word (W2) are
      not detected, leading to a deficit in reporting this word, a phenomenon known as
      repetition blindness (RB). The unrepeated letters in W2 do appear to be detected
      and available to feed activation to words compatible with them (Morris & Harris,
      1999). When a fragment was strategically placed in the RSVP stream, as in GROW
      throw ank, observers reported seeing thank more often than in the control
      condition BEAT throw ank. Illusory words were facilitated by repetition blindness
      only when the recombining letters maintained their position in the words.
      Illusory word report was insensitive to the phonological similarity of the
      recombining letters; equal quantities of illusory words were created by sequences
      like china CHEAT THR (-->threat) and swung SWEAT THR (-->threat). In addition to
      being an interesting phenomenon in its own right, the illusory words paradigm may
      have considerable use as a tool for probing the perceptual units underlying
      visual word recognition.

PMID- 11340857
TI  - Priming complex words: evidence for supralexical representation of morphology.
AB  - Effects of morphologically related primes were examined in two masked prime
      experiments. Responses to both free root and derived suffixed word targets were
      facilitated when primes were derived suffixed words containing the target's root,
      and this facilitation effect showed a time course similar to that for the
      facilitation effect of repetition primes (though systematically smaller in
      magnitude). In a control experiment only the longest prime duration of Experiment
      1 was used; responses to derived suffixed word targets were facilitated by both
      free root primes and derived suffixed word primes sharing the target's root
      (relative to unrelated and form-related control primes). The free root and
      derived suffixed word prime conditions did not differ significantly. In
      Experiment 2, only true derived word primes produced facilitation, whereas
      morphologically simple primes containing a pseudoroot did not influence
      performance relative to the unrelated prime condition. We argue that this
      supports a supralexical account of morphological representation.

PMID- 11340858
TI  - Limitations on the use of verb information during sentence comprehension.
AB  - An eye tracking experiment was conducted in order to investigate the role of verb
      information in resolving structural ambiguity during sentence comprehension.
      Reading time was measured on sentences containing temporarily ambiguous noun
      phrases (e.g. "The athlete revealed the problem") that were continued as tensed
      sentence (S) complements or noun phrase (NP) complements. Ambiguous noun phrases
      were preceded either by verbs occurring most frequently with NP complements (NP
      biased) or verbs occurring most frequently with S complements (S-biased). Reading
      time was also measured on sentences containing unambiguous S complements preceded
      by either NP-biased or S-biased verbs. The results showed that contrary to
      predictions made by verb guidance theories (e.g., constraint satisfaction;
      MacDonald, Pearlmutter, & Seidenberg, 1994a, 1994b; Trueswell & Tanenhaus, 1994),
      for both NP- and S-biased verb conditions, sentences containing temporarily
      ambiguous noun phrase complements were read most quickly, and sentences
      containing temporarily ambiguous S complements were read more slowly than those
      containing unambiguous S complements.

PMID- 11340859
TI  - Probing memory with conceptual cues at multiple retention intervals: a comparison
      of forgetting rates on implicit and explicit tests.
AB  - The time courses for implicit and explicit conceptual tests of memory were
      compared in two experiments. In Experiment 1, participants encoded target words
      by judging the apparent pleasantness of their meaning. Immediately thereafter or
      48 h later, retrieval cues were presented to different groups of participants for
      either an implicit or an explicit free-association task. Whereas explicit test
      performance showed a decline over the 48-h delay, implicit test performance was
      statistically unaltered. In Experiment 2, memory was tested at five retention
      intervals, lasting up to 3 weeks. The forgetting functions of both implicit and
      explicit tests conformed to a logarithmic function. Despite the large conceptual
      priming effect, which resulted from relational encoding instructions, implicit
      memory performance still declined at a much slower rate than did performance on
      the cued-recall test. We argue that because nominal conceptual cues were held
      constant across the implicit and the explicit conditions, the observed
      dissociation in performance supports a memory systems approach.

PMID- 11340860
TI  - Transfer across modality in perceptual implicit memory.
AB  - We examined whether words studied in one modality (visual or auditory) would
      prime performance in the opposite modality in five different perceptual implicit
      memory tests: auditory perceptual identification, auditory stem completion,
      visual perceptual identification, visual stem completion, and visual fragment
      completion. Significant transfer across modality was observed in all five tasks.
      However, a large proportion of the subjects reported using explicit retrieval
      strategies during the implicit tests. Those subjects who claimed not to have used
      explicit retrieval processes during the test phase demonstrated transfer across
      modalities in the stem completion tests and the perceptual identification tests,
      but not in the fragment completion test. The results indicate that implicit
      visual word-fragment completion is unique, in the sense that it relies
      exclusively on perceptual memory processes, whereas the other tasks rely, in
      part, on nonperceptual memory processes.

PMID- 11340861
TI  - "If I had said it I would have remembered it": reducing false memories with a
      distinctiveness heuristic.
AB  - We examined the contributions of decision processes to the rejection of false
      memories. In two experiments, people studied lists of semantically related words
      and then completed a recognition test containing studied words, unrelated lure
      words, and related lure words. People who said words aloud at study were less
      likely to falsely recognize related lures on the test than were those who heard
      words at study. We suggest that people who said words at study employed a
      distinctiveness heuristic during the test whereby they demanded access to
      distinctive say information in order to judge an item as old. Even when
      retrieving say information is not perfectly diagnostic of prior study, as in
      Experiment 2, in which participants both said and heard words at study, people
      persist in using the distinctiveness heuristic to reduce false memories.

PMID- 11340862
TI  - Scale invariance in the retrieval of retrospective and prospective memories.
AB  - How does memory retrieval depend on time scale? One strong hypothesis is that
      such retrieval is scale-invariant (i.e., invariant across different time scales).
      To test this hypothesis, three groups of participants were given 4 min to recall
      what they did yesterday, last week, or last year (retrospective memories), and 4
      min to recall what they intended to do tomorrow, next week, or next year
      (prospective memories). In line with scale invariance, retrieval performance was
      indistinguishable across time scales, for both retrospective and prospective
      memory. An additional finding was that significantly more prospective memories
      were recalled than retrospective memories, confirming previous observations of
      the "intention-superiority effect" (Goschke & Kuhl, 1993).

PMID- 11340863
TI  - The effects of concurrent task interference on category learning: evidence for
      multiple category learning systems.
AB  - Participants learned simple and complex category structures under typical single
      task conditions and when performing a simultaneous numerical Stroop task. In the
      simple categorization tasks, each set of contrasting categories was separated by
      a unidimensional explicit rule, whereas the complex tasks required integrating
      information from three stimulus dimensions and resulted in implicit rules that
      were difficult to verbalize. The concurrent Stroop task dramatically impaired
      learning of the simple explicit rules, but did not significantly delay learning
      of the complex implicit rules. These results support the hypothesis that category
      learning is mediated by multiple learning systems.

PMID- 11340864
TI  - An optimal period for setting sustained variability levels.
AB  - In two experiments, we investigated how explicit reinforcement of highly variable
      behavior at different points in training affected performance after the
      requirement was eliminated. Two versions of a computer game, differing in the
      number of possible solution paths, were used. In each, an optimal period of
      training for producing sustained high variability was found. Exposure to a high
      lag requirement shortly after acquisition sustained variability. Rewarding
      variability at other times did not have a sustained effect. The implications for
      learning and problem solving are discussed.

PMID- 11340865
TI  - Writing and overwriting short-term memory.
AB  - An integrative account of short-term memory is based on data from pigeons trained
      to report the majority color in a sequence of lights. Performance showed strong
      recency effects, was invariant over changes in the interstimulus interval, and
      improved with increases in the intertrial interval. A compound model of binomial
      variance around geometrically decreasing memory described the data; a logit
      transformation rendered it isomorphic with other memory models. The model was
      generalized for variance in the parameters, where it was shown that averaging
      exponential and power functions from individuals or items with different decay
      rates generates new functions that are hyperbolic in time and in log time,
      respectively. The compound model provides a unified treatment of both the accrual
      and the dissipation of memory and is consistent with data from various
      experiments, including the choose-short bias in delayed recall, multielement
      stimuli, and Rubin and Wenzel's (1996) meta-analyses of forgetting.

PMID- 11340866
TI  - The case for sensorimotor coding in working memory.
AB  - The highly influential Baddeley and Hitch model of working memory (Baddeley &
      Hitch, 1974; see also Baddeley, 1986) posited analogical forms of representation
      that can be broadly characterized as sensorimotor, both for verbal and for
      visuospatial material. However, difficulties with the model of verbal working
      memory in particular have led investigators to develop alternative models that
      avoid appealing either to sensory coding or to motoric coding, or to both. This
      paper examines the evidence for sensorimotor coding in working memory, including
      evidence from neuropsychology and from sign language research, as well as from
      standard working memory paradigms, and concludes that only a sensorimotor model
      can accommodate the broad range of effects that characterize verbal working
      memory. In addition, several findings that have been considered to speak against
      sensorimotor involvement are reexamined and are argued to be in fact compatible
      with sensorimotor coding. These conclusions have broad implications, in that they
      support the emerging theoretical viewpoint of embodied cognition.

PMID- 11340867
TI  - The role of involuntary aware memory in the implicit stem and fragment completion
      tasks: a selective review.
AB  - In this article I argue that an awareness of the study episode that arises
      involuntarily during an implicit stem/fragment completion test can under some
      conditions lead to enhanced repetition priming effects, even though subjects are
      not engaged in intentional retrieval. I review findings that are consistent with
      this possibility, which include the effects of depth of processing, and of
      typography match and new association priming following deep encoding. A
      theoretical account of involuntary aware memory couched within Moscovitch's
      (1995b) memory systems framework which suggests that the medial-temporal
      lobe/hippocampal (MTL/H) complex functions as a memory module is outlined. A
      putative mechanism is proposed in which involuntary aware memory of a studied
      item enhances the size of repetition priming effects by guiding its selection in
      preference to the competitors.

PMID- 11340868
TI  - A global factor in the Hermann grid illusion or an artifact?
AB  - In the first of the present experiments, subjects were required to estimate the
      strength of the Hermann grid illusion in grids containing various numbers of
      intersections even though those grids were not actually presented. The positive
      relationship found by Wolfe (1984) for real grids was, nevertheless, replicated.
      It is argued that this suggests that a response bias might have been the source
      of his effect (although other possibilities are also noted). In addition, in a
      second experiment, subjects who were not aware of the fact that grid size was
      being manipulated (i.e., between subjects) showed no consistent effect of that
      factor, thus supporting the same suggestion.

PMID- 11340869
TI  - Processing bottlenecks in dual-task performance: structural limitation or
      strategic postponement?
AB  - Recent evidence indicates that a central bottleneck causes much of the slowing
      that occurs when two tasks are performed at the same time. This bottleneck might
      reflect a structural limitation inherent in the cognitive architecture.
      Alternatively, the bottleneck might reflect strategic (i.e., voluntary)
      postponement, induced by instructions to emphasize one task over the other. To
      distinguish structural limitations from strategic postponement, we examine a new
      paradigm in which subjects are told to place equal emphasis on both tasks and to
      emit both responses at about the same time. An experiment using this paradigm
      demonstrated patterns of interference that cannot easily be attributed to
      strategic postponement, preparation effects, or conflicts in response production.
      The data conform closely to the predictions of structural central bottleneck
      models.

PMID- 11340870
TI  - Multiple bottlenecks in information processing? An electrophysiological
      examination.
AB  - When two stimuli are to be processed in rapid succession, reaction time (RT) to
      the second stimulus is delayed. The slowing of RT has been attributed to a single
      processing bottleneck at response selection (RS) or to a central bottleneck
      following the initiation of the first response. The hypothesis of a response
      initiation bottleneck is mainly based on reports of underadditive interactions
      between stimulus onset asynchrony (SOA) and the number of stimulus-response
      alternatives (simple vs. two-choice response). The present study tested the
      hypothesis of a response initiation bottleneck by recording the lateralized
      readiness potential (LRP), a brain wave, emerging during or immediately following
      RS. The LRP findings were consistent with a central bottleneck but did not
      support the late bottleneck hypothesis. Instead, the LRP provided direct evidence
      that the underadditive interaction of number of alternatives and SOA is due to an
      increase of response anticipations in the simple response condition.

PMID- 11340871
TI  - The role of attentional breadth in perceptual change detection.
AB  - Previous research has shown that changes to scenes are often surprisingly hard to
      detect. The research reported here investigated the relationship between
      individual differences in attention and change detection. We did this by
      assessing participants' breadth of attention in a functional field of view task
      (FFOV) and relating this measure to the speed with which individuals detected
      changes in scenes. We also examined how the salience, meaningfulness, and
      eccentricity of the scene changes affected perceptual change performance. In
      order to broaden the range of individual differences in attentional breadth, both
      young and old adults participated in the study. A strong negative relationship
      was obtained between attentional breadth and the latency with which perceptual
      changes were detected; observers with broader attentional windows detected
      changes faster. Salience and eccentricity had large effects on change detection,
      but meaning aided the performance of young adults only and only when changes also
      had low salience.

PMID- 11340872
TI  - Shared neighborhood effects in masked orthographic priming.
AB  - Several studies have found effects of orthographically related masked nonword
      primes on lexical decisions to target words. These effects have been explained by
      the neighborhood characteristics of the target word (Forster, 1987), but the
      neighborhood characteristics of the prime in combination with the target are also
      found to be important (Hinton, Liversedge, & Underwood, 1998). In this study, we
      present a new account of masked form-priming effects based on the shared
      neighborhood of prime and target. Shared neighbors are words that are activated
      by both prime and target. According to the interactive activation model
      (McClelland & Rumelhart, 1981), shared neighborhood determines the size of
      priming effects. This prediction was tested and confirmed in a masked priming
      experiment that manipulated the shared neighborhood density of complete primes.

PMID- 11340873
TI  - Frequency dependence of dynamic curvature effects on flow through coronary
      arteries.
AB  - The flow through a curved tube model of a coronary artery was investigated
      computationally to determine the importance of time-varying curvature on flow
      patterns that have been associated with the development of atherosclerosis. The
      entry to the tube was fixed while the radius of curvature varied sinusoidally in
      time at a frequency of 1 or 5 Hz. Angiographic data from other studies suggest
      that the radius of curvature waveform contains significant spectral content up to
      6 Hz. The overall flow patterns were similar to those observed in stationary
      curved tubes; velocity profile skewed toward the outer wall, secondary flow
      patterns, etc. The effects of time-varying curvature on the changes in wall shear
      rate were expressed by normalizing the wall shear rate amplitude with the shear
      rate calculated at the static mean radius of curvature. It was found that the
      wall shear rate varied as much as 94 percent of the mean wall shear rate at the
      mid wall of curvature for a mean curvature ratio of 0.08 and a 50 percent change
      in radius of curvature. The effects of 5 Hz deformation were not well predicted
      by a quasi-static approach. The maximum values of the normalized inner wall shear
      rate amplitude were found to scale well with a dimensionless parameter equivalent
      to the product of the mean curvature ratio (delta), normalized change in radius
      of curvature (epsilon), and a Womersley parameter (alpha). This parameter was
      less successful at predicting the amplitudes elsewhere in the tube, thus
      additional studies are necessary. The mean wall shear rate was well predicted
      with a static geometry. These results indicate that dynamic curvature plays an
      important role in determining the inner wall shear rates in coronary arteries
      that are subjected to deformation levels of epsilon delta alpha > 0.05. The
      effects were not always predictable with a quasi-static approach. These results
      provide guidelines for constructing more realistic models of coronary artery flow
      for atherogenesis research.

PMID- 11340874
TI  - Requirements for mesh resolution in 3D computational hemodynamics.
AB  - Computational techniques are widely used for studying large artery hemodynamics.
      Current trends favor analyzing flow in more anatomically realistic arteries. A
      significant obstacle to such analyses is generation of computational meshes that
      accurately resolve both the complex geometry and the physiologically relevant
      flow features. Here we examine, for a single arterial geometry, how velocity and
      wall shear stress patterns depend on mesh characteristics. A well-validated
      Navier-Stokes solver was used to simulate flow in an anatomically realistic human
      right coronary artery (RCA) using unstructured high-order tetrahedral finite
      element meshes. Velocities, wall shear stresses (WSS), and wall shear stress
      gradients were computed on a conventional "high-resolution" mesh series (60,000
      to 160,000 velocity nodes) generated with a commercial meshing package. Similar
      calculations were then performed in a series of meshes generated through an
      adaptive mesh refinement (AMR) methodology. Mesh-independent velocity fields were
      not very difficult to obtain for both the conventional and adaptive mesh series.
      However, wall shear stress fields, and, in particular, wall shear stress gradient
      fields, were much more difficult to accurately resolve. The conventional
      (nonadaptive) mesh series did not show a consistent trend towards mesh
      independence of WSS results. For the adaptive series, it required approximately
      190,000 velocity nodes to reach an r.m.s. error in normalized WSS of less than 10
      percent. Achieving mesh-independence in computed WSS fields requires a
      surprisingly large number of nodes, and is best approached through a systematic
      solution-adaptive mesh refinement technique. Calculations of WSS, and
      particularly WSS gradients, show appreciable errors even on meshes that appear to
      produce mesh-independent velocity fields.

PMID- 11340875
TI  - Oscillatory flow and gas transport through a symmetrical bifurcation.
AB  - Axial gas transport due to the interaction between radial mixing and radially
      nonuniform axial velocities is responsible for gas transport in thick airways
      during High-frequency oscillatory ventilation (HFO). Because the airways can be
      characterized by a bifurcating tube network, the secondary flow in the curved
      portion of a bifurcating tube contributes to cross-stream mixing. In this study
      the oscillatory flow and concentration fields through a single symmetrical airway
      bifurcating tube model were numerically analyzed by solving three-dimensional
      Navier-Stokes and mass concentration equations with the SIMPLER algorithm. The
      simulation conditions were for a Womersley number, alpha = 9.1 and Reynolds
      numbers in the parent tube between 200 and 1000, corresponding to Dn2/alpha 4 in
      the curved portion between 2 and 80, where Dn is Dean number. For comparison with
      the results from the bifurcating tube, we calculated the velocity and
      concentration fields for fully developed oscillatory flow through a curved tube
      with a curvature rate of 1/10, which is identical to the curved portion of the
      bifurcating tube. For Dn2/alpha 4 < or = 10 in the curved portion of the
      bifurcating tube, the flow divider and area changes dominate the axial gas
      transport, because the effective diffusivity is greater than in either a straight
      or curved tube, in spite of low secondary velocities. However, for Dn2/alpha 4 >
      or = 20, the gas transport characteristics in a bifurcation are similar to a
      curved tube because of the significant effect of secondary flow.

PMID- 11340876
TI  - Specific hydraulic conductivity of corneal stroma as seen by quick-freeze/deep
      etch.
AB  - Previous studies of the hydraulic conductivity of connective tissues have failed
      to show a correspondence between ultrastructure and specific hydraulic
      conductivity. We used the technique of quick-freeze/deep-etch to examine the
      ultrastructure of the corneal stroma and then utilized morphometric studies to
      compute the specific hydraulic conductivity of the corneal stroma. Our studies
      demonstrated ultrastructural elements of the extracellular matrix of the corneal
      stroma that are not seen using conventional electron microscopic techniques.
      Furthermore, we found that these structures may be responsible for generating the
      high flow resistance characteristic of connective tissues. From analysis of
      micrographs corrected for depth-of-field effects, we used Carmen-Kozeny theory to
      bound a morphometrically determined specific hydraulic conductivity of the
      corneal stroma between 0.46 x 10(-14) and 10.3 x 10(-14) cm2. These bounds
      encompass experimentally measured values in the literature of 0.5 x 10(-14) to 2
      x 10(-14) cm2. The largest source of uncertainty was due to the depth-of-field
      estimates that ranged from 15 to 51 nm; a better estimate would substantially
      reduce the uncertainty of these morphometrically determined values.

PMID- 11340877
TI  - Comparison of viscoelastic, structural, and material properties of double-looped
      anterior cruciate ligament grafts made from bovine digital extensor and human
      hamstring tendons.
AB  - Due to ready availability, decreased cost, and freedom from transmissible
      diseases in humans such as hepatitis and AIDS, it would be advantageous to use
      tendon grafts from farm animals as a substitute for human tendon grafts in in
      vitro experiments aimed at improving the outcome of anterior cruciate ligament
      (ACL) reconstructive surgery. Thus the objective of this study was to determine
      whether an anterior cruciate ligament (ACL) graft composed of two loops of bovine
      common digital extensor tendon has the same viscoelastic, structural, and
      material properties as a graft composed of a double loop of semitendinosus and
      gracilis tendons from humans. To satisfy this objective, grafts were constructed
      from each tissue source. The cross-sectional area was measured using an area
      micrometer, and each graft was then pulled using a materials testing system while
      submerged in a saline bath. Using two groups of tendon grafts (n = 10),
      viscoelastic tests were conducted over a three-day period during which a constant
      displacement load relaxation test was followed by a constant amplitude, cyclic
      load creep test (first day), a constant load creep test (second day), and an
      incremental cyclic load creep test (third day). Load-to-failure tests were
      performed on two different groups of grafts (n = 8). When the viscoelastic
      behavior was compared, there were no significant differences in the rate of load
      decay or the final load (relaxation test) and rates of displacement increase or
      final displacements (creep tests) (p > 0.115). To compare both the structural and
      material properties in the toe region (i.e., < 250 N) of the load-elongation
      curve, the tangent stiffness and modulus functions were computed from parameters
      used in an exponential model fit to the load (stress)-elongation (strain) data.
      Although one of the two parameters in the functions was different statistically,
      this difference translated into a difference of only 0.03 mm in displacement at
      250 N of load. In the linear region (i.e., 50-75 percent of ultimate load) of the
      load-elongation curve, the linear stiffness of the two graft types compared
      closely (444 N/mm for bovine and 418 N/mm for human) (p = 0.341). At failure, the
      ultimate loads (2901 N and 2914 N for bovine and human, respectively) and the
      ultimate stresses (71.8 MPa and 65.6 MPa for bovine and human, respectively) were
      not significantly different (p > 0.261). The theoretical effect of any
      differences in properties between these two grafts on the results of two types of
      in vitro experiments (i.e., effect of surgical variables on knee laxity and
      structural properties of fixation devices) are discussed. Despite some
      statistical differences in the properties evaluated, these differences do not
      translate into important effects on the dependent variables of interest in the
      experiments. Thus the bovine tendon graft can be substituted for the human tendon
      graft in both types of experiments.

PMID- 11340878
TI  - Simple shear testing of parallel-fibered planar soft tissues.
AB  - The simple shear test may provide unique information regarding the material
      response of parallel-fibered soft tissues because it allows the elimination of
      the dominant fiber material response from the overall stresses. However,
      inhomogeneities in the strain field due to clamping and free edge effects have
      not been documented. The finite element method was used to study finite simple
      shear of simulated ligament material parallel to the fiber direction. The effects
      of aspect ratio, clamping prestrain, and bulk modulus were assessed using a
      transversely isotropic, hyperelastic material model. For certain geometries,
      there was a central area of uniform strain. An aspect ratio of 1:2 for the fiber
      to cross-fiber directions provided the largest region of uniform strain. The
      deformation was nearly isochoric for all bulk moduli indicating this test may be
      useful for isolating solid viscoelasticity from interstitial flow effects.
      Results suggest this test can be used to characterize the matrix properties for
      the type of materials examined in this study, and that planar measurements will
      suffice to characterize the strain. The test configuration may be useful for the
      study of matrix, fiber-matrix, and fiber-fiber material response in other types
      of parallel-fibered transversely isotropic soft tissues.

PMID- 11340879
TI  - High-resolution three-dimensional-pQCT images can be an adequate basis for in
      vivo microFE analysis of bone.
AB  - Micro-finite element (microFE) models based on high-resolution images have
      enabled the calculation of elastic properties of trabecular bone in vitro.
      Recently, techniques have been developed to image trabecular bone structure in
      vivo, albeit at a lesser resolution. The present work studies the usefulness of
      such in-vivo images for microFE analyses, by comparing their microFE results to
      those of models based on high-resolution micro-CT (microCT) images. Fifteen
      specimens obtained from human femoral heads were imaged first with a 3D-pQCT
      scanner at 165 microns resolution and a second time with a microCT scanner at 56
      microns resolution. A third set of images with a resolution of 165 microns was
      created by downscaling the microCT measurements. The microFE models were created
      directly from these images. Orthotropic elastic properties and the average tissue
      von Mises stress of the specimens were calculated from six FE-analyses per
      specimen. The results of the 165 microns models were compared to those of the 56
      microns model, which was taken as the reference model. The results calculated
      from the pQCT-based models, correlated excellent with those calculated from the
      reference model for both moduli (R2 > 0.95) and for the average tissue von Mises
      stress (R2 > 0.83). Results calculated from the downscaled micro-CT models
      correlated even better with those of the reference models (R2 > 0.99 for the
      moduli and R2 > 0.96 for the average von Mises stress). In the case of the 3D
      pQCT based models, however, the slopes of the regression lines were less than one
      and had to be corrected. The prediction of the Poisson's ratios was less accurate
      (R2 > 0.45 and R2 > 0.67) for the models based on 3D-pQCT and downscaled microCT
      images respectively). The fact that the results from the downscaled and original
      microCT images were nearly identical indicates that the need for a correction in
      the case of the 3D-pQCT measurements was not due to the voxel size of the images
      but due to a higher noise level and a lower contrast in these images, in
      combination with the application of a filtering procedure at 165 micron images.
      In summary: the results of microFE models based on in-vivo images of the 3D-pQCT
      can closely resemble those obtained from microFE models based on higher
      resolution microCT system.

PMID- 11340880
TI  - Dynamic measurements of three-dimensional scapular kinematics: a validation
      study.
AB  - The validation of two noninvasive methods for measuring the dynamic three
      dimensional kinematics of the human scapula with a magnetic tracking device is
      presented. One method consists of simply fixing a sensor directly to the acromion
      and the other consists of mounting a sensor to an adjustable plastic jig that
      fits over the scapular spine and acromion. The concurrent validity of both
      methods was assessed separately by comparison with data collected simultaneously
      from an invasive approach in which pins were drilled directly into the scapula.
      The differences between bone and skin based measurements represents an estimation
      of skin motion artifact. The average motion pattern of each surface method was
      similar to that measured by the invasive technique, especially below 120 degrees
      of elevation. These results indicate that with careful consideration, both
      methods may offer reasonably accurate representations of scapular motion that may
      be used to study shoulder pathologies and help develop computational models.

PMID- 11340881
TI  - Biphasic poroviscoelastic simulation of the unconfined compression of articular
      cartilage: I--Simultaneous prediction of reaction force and lateral displacement.
AB  - This study investigated the ability of the linear biphasic poroelastic (BPE)
      model and the linear biphasic poroviscoelastic (BPVE) model to simultaneously
      predict the reaction force and lateral displacement exhibited by articular
      cartilage during stress relaxation in unconfined compression. Both models
      consider articular cartilage as a binary mixture of a porous incompressible solid
      phase and an incompressible inviscid fluid phase. The BPE model assumes the solid
      phase is elastic, while the BPVE model assumes the solid phase is viscoelastic.
      In addition, the efficacy of two additional models was also examined, i.e., the
      transversely isotropic BPE (TIBPE) model, which considers transverse isotropy of
      the solid matrix within the framework of the linear BPE model assumptions, and a
      linear viscoelastic solid (LVE) model, which assumes that the viscoelastic
      behavior of articular cartilage is solely governed by the intrinsic viscoelastic
      nature of the solid matrix, independent of the interstitial fluid flow. It was
      found that the BPE model was able to accurately account for the lateral
      displacement, but unable to fit the short-term reaction force data of all
      specimens tested. The TIBPE model was able to account for either the lateral
      displacement or the reaction force, but not both simultaneously. The LVE model
      was able to account for the complete reaction force, but unable to fit the
      lateral displacement measured experimentally. The BPVE model was able to
      completely account for both lateral displacement and reaction force for all
      specimens tested. These results suggest that both the fluid flow-dependent and
      fluid flow-independent viscoelastic mechanisms are essential for a complete
      simulation of the viscoelastic phenomena of articular cartilage.

PMID- 11340882
TI  - Biphasic poroviscoelastic simulation of the unconfined compression of articular
      cartilage: II--Effect of variable strain rates.
AB  - This study investigated the abilities of the linear biphasic poroviscoelastic
      (BPVE) model and the linear biphasic poroelastic (BPE) model to simulate the
      effect of variable ramp strain rates on the unconfined compression stress
      relaxation response of articular cartilage. Curve fitting of experimental data
      showed that the BPVE model was able to successfully account for the ramp strain
      rate-dependent viscoelastic behavior of articular cartilage under unconfined
      compression, while the BPE model was able to account for the complete
      viscoelastic response at a slow strain rate, but only the long-term viscoelastic
      response at faster strain rates. We concluded that the short-term viscoelastic
      behavior of articular cartilage, when subjected to a fast ramp strain rate, is
      primarily governed by a fluid flow-independent (intrinsic) viscoelastic
      mechanism, whereas the long-term viscoelastic behavior is governed by a fluid
      flow-dependent (biphasic) viscoelastic mechanism. Furthermore, a linear
      viscoelastic representation of the solid stress was found to be a valid model
      assumption for the simulation of ramp strain rate-dependent relaxation behaviors
      of articular cartilage within the range of ramp strain rates investigated.

PMID- 11340883
TI  - Medical ethics--some thoughts.

PMID- 11340884
TI  - New approaches in the management of choroidal neovascular membrane in age-related
      macular degeneration.
AB  - Age-related macular degeneration (AMD) is a leading cause of blindness in the
      elderly population. The prevalence is reported to be 1.2-1.4% in several
      population-based epidemiological studies. Currently 25-30 million people
      worldwide are blind due to AMD. With the aging world population it is bound to
      increase significantly, and could become a significant public health problem in
      next two decades, with serious socio-economic implications. Several strategies
      are today available to treat the wet form of AMD, which is responsible for
      significant visual loss. These were until recently confined to laser
      photocoagulation, and subretinal surgery, but today two other modalities, namely,
      radiation and photodynamic therapy, are available. These treatment modalities
      however, are aimed at preservation of vision only, and not at reversing the
      process of the disease. Further research on antiangiogenic drugs and gene therapy
      could significantly help AMD patients.

PMID- 11340885
TI  - Comparison of optical and ultrasound pachometry.
AB  - PURPOSE: (1) To determine the agreement between optical and ultrasound pachometry
      for central corneal thickness measurements used to "correct" applanation
      intraocular pressure (IOP) readings. (2) To determine the inter- and intra
      observer variability of optical and ultrasound pachometry. METHOD: Central
      corneal thickness (CCT) was measured in a masked manner using optical and
      ultrasound pachometry in 50 normal eyes. To assess intra- and inter-observer
      variability, multiple masked measurements were obtained in 51 eyes (optical
      pachometry) and 34 eyes (ultrasound pachometry). Agreement was determined by a
      published technique that uses the mean of the differences, standard error (SE)
      and standard deviation (SD). RESULTS: The mean difference in CCT between optical
      and ultrasound pachometry was 0.001 mm (SD 0.031 mm; SE 0.00439 mm). The mean
      inter-observer difference for the optical pachometer was 0.019 mm (SD 0.049 mm;
      SE 0.0069); the mean intra-observer difference was 0.003 mm (SD 0.017; SE
      0.0.0024). The mean inter-observer difference for ultrasound pachometry was 0.001
      mm (SD 0.009; SE 0.0015) and the mean intra-observer difference was 0.002 mm (SD
      0.011; SE 0.0019). CONCLUSIONS: Ultrasound pachometry is the more reliable method
      for the measurement of central corneal thickness used to correct applanation IOP
      values. Optical pachometry had good intra-observer variability. The range of
      error in IOP correction for corneal thickness (inter-observer) that can occur
      using the ultrasound pachometer is -1.2 mmHg to +1.4 mmHg as compared to -5.6
      mmHg to +8.5 mmHg with the optical pachometer.

PMID- 11340886
TI  - Sodium bicarbonate--an alternative to hyaluronidase in ocular anaesthesia for
      cataract surgery.
AB  - PURPOSE: To evaluate and compare the safety, efficacy and cost-effectiveness of
      7.5% sodium bicarbonate buffered lidocaine (pH 7.2) with hyaluronidase mixed
      lidocaine (pH 4.6) for local anaesthesia in cataract surgery. METHODS: This
      prospective study comprised two parts. Part I: We evaluated the ocular and
      systematic anaesthetic safety and efficacy of 7.5% sodium bicarbonate buffered
      lidocaine on 112 consecutive patients undergoing cataract extraction with
      intraocular lens (IOL) implantation. At 12-week postoperative follow up final
      visual acuity and detailed fundus examination was done. Part II: It was conducted
      as a double blind, randomized comparative clinical trial involving 120 patients
      undergoing cataract surgery under retrobulbar anaesthesia. Patients were randomly
      assigned to one of the two groups: 60 eyes received 2 ml of 2% lidocaine with
      1:200,000 epinephrine and 1 ml of 7.5% sodium bicarbonate, (0.299 mmol/ml); the
      remaining 60 eyes received 2 ml of 2% lidocaine with 1:200,000 epinephrine and
      450 units of hyaluronidase (15 U/ml). In the event of incomplete akinesia,
      retrobulbar blocks were supplemented at 10 minutes. Onset and duration of
      anaesthesia and akinesia were assessed and compared in both groups. RESULTS: The
      pH-adjusted lidocaine group did not show any demonstrable variation in blood
      pressure (BP) or other systemic reaction. No anaesthesia-related adverse ocular
      effects were observed either during or after surgery. Thirty-one eyes (51.6%)
      achieved complete anaesthesia and akinesia within 5 minutes compared to 13 eyes
      (21.6%) in the hyaluronidase group. However, the overall mean onset time of
      anaesthesia and akinesia, repeat block rate and the duration of the anaesthesia
      were comparable in both the groups--p: 0.14). Twelve weeks postoperatively 88.39%
      of patients showed a best corrected visual acuity of 6/18 or better (73.21%-6/12
      or better). CONCLUSION: In this study, sodium bicarbonate buffered 2% lidocaine
      was found to be a safe and effective local anaesthetic, with reduced time of
      onset, and improved quality of both anaesthesia and akinesia. Sodium bicarbonate
      (7.5%) may be used as an alternative to hyaluronidase in ocular anaesthesia. It
      is readily available and is cost effective.

PMID- 11340887
TI  - Keratocyte loss in Acanthamoeba keratitis: phagocytosis, necrosis or apoptosis?
AB  - PURPOSE: Pathogenesis of Acanthamoeba keratitis involves breakdown of epithelial
      barrier, stromal invasion by Acanthamoeba, loss of keratocytes, inflammatory
      response and finally stromal necrosis. The loss of keratocytes, believed to be
      due to the phagocytic activity of the parasite, occurs disproportionate to and
      independent of the parasite load, thereby suggesting additional modes of cell
      loss. To test our hypothesis that the loss of keratocytes in Acanthamoeba
      keratitis is due to apoptosis, we did both histology and histochemistry on the
      corneal tissues. METHODS: Routine Haematoxylin and Eosin, Gomori's Methenamine
      Silver and Periodic acid Schiff stained sections of five corneal tissues from
      penetrating keratoplasty and eviscerated eyes were reviewed. TUNEL staining was
      done for morphological detection of apoptosis in three cases, using formalin
      fixed, paraffin-processed tissues. RESULTS: Histological changes were epithelial
      ulceration, loss of keratocytes in all layers, inflammation in anterior two
      thirds of the stroma with necrosis, and deeper quiet stroma. Acanthamoeba
      trophozoites were found in the anterior stroma while the cysts were more in the
      deeper stroma, with minimal or no inflammatory response. TUNEL staining was
      positive in keratocytic nuclei in all layers. CONCLUSIONS: This study
      demonstrates that one of the modes of keratocyte loss in Acanthamoeba keratitis
      is by apoptosis, possibly in addition to the necrotic process and phagocytic
      activity of the parasite. The death of inflammatory cells also appears to be
      mediated by apoptosis.

PMID- 11340888
TI  - Contact trans-scleral diode laser cyclophotocoagulation treatment for refractory
      glaucomas in the Indian population.
AB  - PURPOSE: This study aimed to evaluate the clinical efficacy of contact diode
      trans-scleral cyclophotocoagulation (TSCPC) for treatment of refractory
      glaucomas. METHOD: Fifty two eyes of 52 patients, (post-penetrating keratoplasty
      glaucoma: 16 eyes; adherent leucoma with secondary glaucoma: 8 eyes; aphakic
      glaucoma: 6 eyes; neovascular glaucoma: 6 eyes; narrow angle glaucoma: 6 eyes;
      and other secondary glaucomas: 10 eyes) were followed up from 3.5-18 months
      (average 12 months) after TSCPC. The treatment parameters using the contact G
      probe were--energy: 3-4J; area: 40 spots spread over 360 degrees; site: 1.2-1.5
      mm posterior to limbus. Retreatments (22 eyes; 42%) were given whenever
      intraocular pressure (IOP) exceeded 22 mmHg despite maximum tolerable topical
      therapy. RESULTS: IOP decreased from a baseline of 44.7 (+/- 7.3) mmHg to 15 (+/-
      3.7) mmHg at first week and was 15.2 +/- (8.2) mmHg at the last follow up.
      Successful control of IOP (< 22 mmHg) occurred in 30 (58%) eyes after a single
      treatment and in 48 (92%) eyes following retreatment. Complications included
      reduction in visual acuity from light perception (LP) only to no light perception
      (NLP) in two eyes and phthisis bulbi in one eye. CONCLUSION: Contact trans
      scleral diode laser cyclophotocoagulation is effective in lowering IOP in eyes
      with intractable glaucoma with few side effects in Indian subjects.

PMID- 11340889
TI  - Visual field assessment in glaucoma: comparative evaluation of manual kinetic
      Goldmann perimetry and automated static perimetry.
AB  - PURPOSE: To compare the detection and assessment of progression of visual field
      defects in primary open-angle glaucoma with manual suprathreshold perimetry on
      Goldmann perimeter and automated static threshold perimetry on Humphery visual
      field (HVF) analyzer. METHODS: 105 eyes of 54 patients of primary open-angle
      glaucoma were followed up with 3-monthly perimetry on Goldmann perimeter and HVF
      analyzer, for a period of 9 months. RESULTS: HVF analyzer picked up visual field
      defects in 48 (46%) eyes whereas Goldmann perimeter picked up visual field
      defects in 26 (25%) eyes. HVF analyzer demonstrated progression in 14 eyes
      whereas Goldmann perimeter detected progression in 7 eyes during follow up of 9
      months. CONCLUSIONS: HVF analyzer is superior to Goldmann perimeter to document
      and to demonstrate progression of visual field defects in primary open-angle
      glaucoma.

PMID- 11340890
TI  - Raised platelet thiobarbituric acid-reacting substances in proliferative Eales'
      disease.
AB  - BACKGROUND: Platelets are an elective site for oxidative stress owing to their
      high content of polyunsaturated fatty acid. Increased lipid peroxidation and
      elevated platelet thiobarbituric acid-reacting substances (TBARS) signal
      oxidative stress. This possibly leads to retinal neovascularization in Eales'
      disease. METHODS: TBARS levels were estimated in consecutive cases of Eales'
      disease with neovascularisation (n = 26), Eales' disease without
      neovascularisation (n = 17) and healthy controls (n = 17). RESULTS: Platelet
      TBARS levels in the cases of Eales' disease with neovascularisation, Eales'
      disease without neovascularisation, and healthy controls were 0.66 +/- 0.1, 0.57
      +/- 0.11 and 0.42 +/- 0.14 n moles TBARS formed/hour/10(8) platelets
      respectively. Student's t-test showed a significant increase in platelet TBARS
      levels in cases with neovascularisation as compared to cases without
      neovascularization (p < 0.05) and healthy controls (p < 0.01). CONCLUSION: The
      increase in platelet TBARS levels in proliferative Eales' disease is consistent
      with an emerging view that lipid peroxides may be associated with retinal
      neovascularisation.

PMID- 11340891
TI  - Acute panuveitis with haemorrhagic hypopyon as a presenting feature of acquired
      immunodeficiency syndrome (AIDS).
AB  - Anterior uveitis is a known clinical entity in herpes zoster ophthalmicus
      associated with AIDS. However, reports of acute haemorrhagic hypopyon uveitis in
      such cases are lacking. Herein we describe a young male patient presenting with
      acute panuveitis with haemorrhagic hypopyon, who was found HIV positive on
      investigation.

PMID- 11340892
TI  - Immune recovery vitritis presenting as panuveitis following therapy with protease
      inhibitors.
AB  - Immune reconstitution in acquired immunodeficiency syndrome (AIDS) patients on
      highly active anti-retroviral therapy (HAART) with cytomegalovirus (CMV)
      retinitis manifested as posterior segment intraocular inflammation has been
      reported. We report an adult HIV-positive Indian male with clinically inactive
      CMV retinitis who developed panuveitis with hypopyon. This was related to immune
      recovery mediated by combination anti-retroviral treatment, including protease
      inhibitors.

PMID- 11340893
TI  - Retinal pigment epithelial tears associated with idiopathic central serous
      chorioretinopathy.
AB  - Two patients with idiopathic central serous chorioretinopathy with retinal
      pigment epithelial tears are described.

PMID- 11340894
TI  - Management of diabetic retinopathy.
AB  - Diabetic retinopathy remains a major cause of blindness despite increased
      understanding of this disease and identification of successful treatments. The
      Diabetic Retinopathy Study identified risk factors associated with a high risk of
      blindness and confirmed the benefits of panretinal photocoagulation. The Early
      Treatment Diabetic Retinopathy Study defined the retinal characteristics,
      indications of treatment and results of laser treatment of clinically significant
      macular oedema. The Diabetic Retinopathy Vitrectomy study established the
      benefits and timing of vitrectomy for non-clearing vitreous haemorrhage and
      severe proliferative diabetic retinopathy. The Diabetes Control and Complications
      Trial and the United Kingdom Prospective Diabetes Study have also demonstrated
      the value of tight control of blood sugar and blood pressure in diabetic
      retinopathy. These studies developed specific recommendations for the management
      of diabetic retinopathy. Optimum use of this information can minimize visual loss
      due to diabetic retinopathy.

PMID- 11340895
TI  - Ascaris lumbricoides in the lacrimal passage.

PMID- 11340896
TI  - An unusual presentation of orbital cysticercosis.

PMID- 11340897
TI  - Docetaxel: assessing a range of activity.

PMID- 11340898
TI  - The current status of docetaxel for advanced non-small cell lung cancer.
AB  - Docetaxel is an active single agent in both first- and second-line therapy of
      patients with advanced non-small cell lung cancer (NSCLC). Randomized trials
      versus best supportive care have documented an improvement in overall survival
      for docetaxel therapy in both settings. Docetaxel also produced a significant 1
      year survival rate improvement when compared with vinorelbine or ifosfamide as
      second-line therapy. Docetaxel has been extensively investigated in phase I/II
      studies in combination with cisplatin, carboplatin, irinotecan and gemcitabine.
      Substantial activity has been demonstrated. In a randomized phase II trial
      comparing docetaxel plus cisplatin with docetaxel plus gemcitabine, the efficacy
      of the two regimens was almost identical (response rates 32 and 34%; 1-year
      survival rates 42 and 38%). However, the combination of docetaxel with
      gemcitabine was associated with significantly less grade III/IV neutropenia,
      diarrhea and nausea/vomiting. Three drug regimens combining docetaxel with, for
      example, gemcitabine and carboplatin or with ifosfamide and cisplatin, are
      producing very high response rates in phase II trials. Whether three-drug
      combinations including docetaxel will result in an improved outcome for patients
      with advanced NSCLC remains to be determined.

PMID- 11340899
TI  - Docetaxel in prostate cancer.
AB  - In contrast to several other tumor types, there has been relatively little
      experience with docetaxel in hormone-refractory prostate cancer. However, two
      phase II trials investigated the combination of docetaxel with estramustine, and
      reported prostate-specific antigen response rates of 69 and 74% and objective
      responses in 23% and 57% of patients. This activity is comparable with that of
      other estramustine combinations. However, there is uncertainty about whether
      estramustine itself should be omitted from therapy because of its emetogenic and
      thromboembolic potential, and also over the optimal schedule of docetaxel to
      avoid neutropenia. Preliminary data suggest that weekly docetaxel, with or
      without limited exposure to estramustine, may provide the right balance between
      efficacy and tolerability. Phase III studies now in progress are comparing
      regimens containing docetaxel and estramustine with a recent standard therapy
      consisting of mitoxantrone plus prednisone. In the future, the efficacy of
      docetaxel plus estramustine may be enhanced by adding agents to this regimen.

PMID- 11340900
TI  - Docetaxel in squamous cell cancer of the head and neck.
AB  - Single-agent docetaxel induces a response in 21-42% of patients with recurrent
      squamous cell cancer of the head and neck (SCCHN). When used in combination with
      5-fluorouracil (5-FU), response rates (RRs) of between 24 and 27% have been
      reported. In contrast, in combination with cisplatin, docetaxel has achieved a RR
      of 33% in previously treated patients and 86% in a subgroup of chemotherapy-naive
      advanced stage patients. The docetaxel/cisplatin combination appears to be highly
      active. High-dose induction chemotherapy for patients with locally advanced but
      potentially curable SCCHN is producing promising results: following combination
      therapy involving docetaxel, cisplatin, 5-FU and leucovorin (TPFL), RR are high
      and 75% of patients are alive at 2 years. Intermediate-dose induction
      chemotherapy involving docetaxel is also promising: the TAX 708 trial found an
      excellent 93% RR in 41 evaluable patients treated with docetaxel plus cisplatin
      and 5-FU (TPF). The rate of pathological complete response was also high. The
      toxicities with TPF therapy were similar to those seen with cisplatin/5-FU
      regimens without docetaxel. A phase III trial of this approach is currently being
      conducted.

PMID- 11340901
TI  - Issues involved in research into the neoadjuvant treatment of breast cancer.
AB  - Randomized studies have failed to find convincing evidence that neo-adjuvant
      chemotherapy results in improved overall survival. This may be related to limited
      efficacy of the regimens used. A sequence of an anthracycline-based primary
      chemotherapy followed by docetaxel has shown promising results which are briefly
      discussed. The assessment of the efficacy of neoadjuvant therapy should be based
      on the evaluation of pathological response and a simple, reproducible method of
      grading differential response would be of great value. Positive identification of
      tumor stroma is essential in defining pathological complete response (pCR). This
      paper presents a grading scheme based purely on microscopic assessment which
      classifies patients into five groups with significantly different disease-free
      and overall survival. A system dividing patients into only two groups, i.e. those
      with pCR or those with any evidence of invasive tumor, may lose information of
      prognostic value. Assessing the response of metastatic disease in the lymph
      nodes, as well as response of the primary tumor, may further refine our ability
      to identify those patients likely to gain most from neoadjuvant chemotherapy.

PMID- 11340902
TI  - Neoadjuvant therapy for non-small cell lung cancer.
AB  - Clinical trials evaluating neoadjuvant or preoperative therapy for locally
      advanced non-small cell lung cancer (NSCLC) have demonstrated the feasibility,
      tolerability and activity of this approach. Three randomized trials have reported
      improved survival in patients with stage III NSCLC treated with preoperative
      chemotherapy followed by surgical resection compared to surgery alone.
      Combinations of neoadjuvant chemotherapy plus thoracic radiotherapy have also
      been investigated, generally resulting in higher rates of pathologic response,
      but higher toxicity rates as well. The best approach to neoadjuvant therapy
      remains to be determined and may well be substage dependent. In bulky stage III
      NSCLC, the role of surgery itself remains unclear and is the subject of an
      ongoing intergroup trial in the US. Regardless, neoadjuvant therapy has emerged
      as an important paradigm for clinical research since it serves as an in vivo test
      of chemosensitivity in patients, and represents a 'window of opportunity' for
      testing new chemotherapeutic agents and novel strategies. Among the new
      chemotherapeutic agents being investigated in this setting is docetaxel, one of
      the most active agents in first- and second-line chemotherapy of NSCLC, and a
      potent radiosensitizer. Preliminary studies have confirmed the feasibility of
      integrating docetaxel into neoadjuvant treatment strategies and encouraging
      results have been reported.

PMID- 11340903
TI  - [New infection control regulation should improve prevention. Severe vaccination
      reactions require notification].

PMID- 11340904
TI  - [Apnea diagnosis in general practice. Indications, possibilities and limits].
AB  - In view of the limited capacity of hospital sleep labs, and the high prevalence
      of the sleep apnea syndrome, there is a requirement for a preliminary ambulatory
      diagnostic work-up. Nocturnal polygraphy has proved to be a useful screening
      method. The continuous measurement of respiratory flow, oxygen saturation, heart
      rate and body position enables the severity and frequency of respiratory events
      to be monitored. With consideration being given to the patient's symptoms,
      examination findings, cardiovascular disease and the risks resulting from
      disturbed vigilance, a decision can be made on the need for an inpatient
      diagnostic work-up, and its urgency. Ambulatory apnea screening is not suitable
      for the differential diagnosis of nocturnal respiratory disorders, since it does
      not permit the correlation of symptoms to sleep stages and respiratory movements.

PMID- 11340905
TI  - [Obstructive sleep apnea syndrome. Which therapy for which patients].
AB  - Obstructive sleep apnea syndrome is defined by the American Academy of Sleep
      Medicine as a combination of at least five obstructive events per hour of sleep
      and such other symptoms as daytime sleepiness, ischemic heart disease and stroke.
      In addition to weight reduction, the use of oral appliances, and continuous
      positive airway pressure (CPAP), a number of surgical interventions such as
      uvulopalatopharyngoplasty and maxillomandibular advancement are also available
      for the treatment of sleep apnea. Since no prolongation of life has yet been
      shown for most of the therapeutic options, treatment needs to be individualized
      on the basis of symptoms, clinical findings and compliance.

PMID- 11340906
TI  - [Emergencies in general practice, 9. Epileptic seizure].

PMID- 11340907
TI  - [Worm infection. 1: Intestinal helminths].

PMID- 11340908
TI  - [Acute heart attacks. Prognosis can be further improved].

PMID- 11340909
TI  - [Survey by the International Osteoporosis Foundation. Osteoporosis is criminally
      neglected].

PMID- 11340910
TI  - [Status of osteoporosis therapy. A medical scandal].

PMID- 11340911
TI  - [Prevention in coronary heart disease. Can a CSE inhibitor arrest calcium
      deposits?].

PMID- 11340912
TI  - [Bronchial asthma. Combination therapy becomes simpler].

PMID- 11340913
TI  - [Type 2 diabetes. Acarbose interrupts the vicious circle].

PMID- 11340914
TI  - [A new antihistamine. Inhibiting inflammation in rhinorrhea and nasal
      congestion].

PMID- 11340915
TI  - [Therapeutic angiogenesis. Initial success with coronary vessels].

PMID- 11340916
TI  - [17. Diabetes mellitus--classification, early detection and diagnosis].

PMID- 11340917
TI  - Virtually perfect time sharing in dual-task performance: uncorking the central
      cognitive bottleneck.
AB  - A fundamental issue for psychological science concerns the extent to which people
      can simultaneously perform two perceptual-motor tasks. Some theorists have
      hypothesized that such dual-task performance is severely and persistently
      constrained by a central cognitive "bottle-neck," whereas others have
      hypothesized that skilled procedural decision making and response selection for
      two or more tasks can proceed at the same time under adaptive executive control.
      The three experiments reported here support this latter hypothesis. Their results
      show that after relatively modest amounts of practice, at least some participants
      achieve virtually perfect time sharing in the dual-task performance of basic
      choice reaction tasks. The results also show that observed interference between
      tasks can be modulated by instructions about differential task priorities and
      personal preferences for daring (concurrent) or cautious (successive) scheduling
      of tasks. Given this outcome, future research should investigate exactly when and
      how such sophisticated skills in dual-task performance are acquired.

PMID- 11340918
TI  - When sound affects vision: effects of auditory grouping on visual motion
      perception.
AB  - Two identical visual targets moving across each other can be perceived either to
      bounce off or to stream through each other. A brief sound at the moment the
      targets coincide biases perception toward bouncing. We found that this bounce
      inducing effect was attenuated when other identical sounds (auditory flankers)
      were presented 300 ms before and after the simultaneous sound. The attenuation
      occurred only when the simultaneous sound and auditory flankers had similar
      acoustic characteristics and the simultaneous sound was not salient. These
      results suggest that there is an aspect of auditory-grouping (saliency-assigning)
      processes that is context-sensitive and can be utilized by the visual system for
      solving ambiguity. Furthermore, control experiments revealed that such auditory
      context did not affect the perceptual qualities of the simultaneous sound.
      Because the attenuation effect is not manifest in the perception of acoustic
      characteristics of individual sound elements, we conclude that it is a genuine
      cross-modal effect.

PMID- 11340919
TI  - Granting forgiveness or harboring grudges: implications for emotion, physiology,
      and health.
AB  - Interpersonal offenses frequently mar relationships. Theorists have argued that
      the responses victims adopt toward their offenders have ramifications not only
      for their cognition, but also for their emotion, physiology, and health. This
      study examined the immediate emotional and physiological effects that occurred
      when participants (35 females, 36 males) rehearsed hurtful memories and nursed
      grudges (i.e., were unforgiving) compared with when they cultivated empathic
      perspective taking and imagined granting forgiveness (i.e., were forgiving)
      toward real-life offenders. Unforgiving thoughts prompted more aversive emotion,
      and significantly higher corrugator (brow) electromyogram (EMG), skin
      conductance, heart rate, and blood pressure changes from baseline. The EMG, skin
      conductance, and heart rate effects persisted after imagery into the recovery
      periods. Forgiving thoughts prompted greater perceived control and comparatively
      lower physiological stress responses. The results dovetail with the
      psychophysiology literature and suggest possible mechanisms through which chronic
      unforgiving responses may erode health whereas forgiving responses may enhance
      it.

PMID- 11340920
TI  - End effects of rated life quality: the James Dean Effect.
AB  - In three studies, we explored how the ending of a life influences the perceived
      desirability of that life. We consistently observed that participants neglected
      duration in judging the global quality of life. Across all the studies, the end
      of life was weighted heavily, producing ratings that contradict a simple hedonic
      calculus in which years of pleasure and pain are summed. Respondents rated a
      wonderful life that ended abruptly as better than one with additional mildly
      pleasant years (the "James Dean Effect"). Similarly, a terrible life with
      additional moderately bad years was rated as more desirable than one ending
      abruptly without those unpleasant years (the "Alexander Solzhenitsyn Effect").
      Finally, embedding moderately intense years in the middle of life did not produce
      effects as strong as adding those years to the end of life, suggesting that a
      life's ending is weighted especially heavily in judging quality of life.

PMID- 11340921
TI  - Two kinds of reasoning.
AB  - According to one view of reasoning, people can evaluate arguments in at least two
      qualitatively different ways: in terms of their deductive correctness and in
      terms of their inductive strength. According to a second view, assessments of
      both correctness and strength are a function of an argument's position on a
      single psychological continuum (e.g., subjective conditional probability). A
      deductively correct argument is one with the maximum value on this continuum; a
      strong argument is one with a high value. The present experiment tested these
      theories by asking participants to evaluate the same set of arguments for
      correctness and strength. The results produced an interaction between type of
      argument and instructions: In some conditions, participants judged one argument
      deductively correct more often than a second, but judged the second argument
      inductively strong more often than the first. This finding supports the view that
      people have distinct ways to evaluate arguments.

PMID- 11340922
TI  - Do amnesics exhibit cognitive dissonance reduction? The role of explicit memory
      and attention in attitude change.
AB  - In two studies, we investigated the roles of explicit memory and attentional
      resources in the process of behavior-induced attitude change. Although most
      theories of attitude change (cognitive dissonance and self-perception theories)
      assume an important role for both mechanisms, we propose that behavior-induced
      attitude change can be a relatively automatic process that does not require
      explicit memory for, or consciously controlled processing of, the discrepancy
      between attitude and behavior. Using a free-choice paradigm, we found that both
      amnesics and normal participants under cognitive load showed as much attitude
      change as did control participants.

PMID- 11340923
TI  - Infants' knowledge about occlusion and containment events: a surprising
      discrepancy.
AB  - The present research examined whether infants acquire general principles or more
      specific rules when learning about physical events. Experiments 1 and 2
      investigated 4.5-month-old infants' ability to judge how much of a tall object
      should be hidden when lowered behind an occluder versus inside a container. The
      results indicated that at this age infants are able to reason about height in
      occlusion but not containment events. Experiment 3 showed that this latter
      ability does not emerge until about 7.5 months of age. The marked discrepancy in
      infants' reasoning about height in occlusion and containment events suggests that
      infants sort events into distinct categories, and acquire separate rules for each
      category.

PMID- 11340924
TI  - Gone but not forgotten: the transient nature of retrieval-induced forgetting.
AB  - Recent research has demonstrated that the act of remembering can prompt temporary
      forgetting or, more specifically, the inhibition of particular items in memory.
      Extending work of this kind, the present research investigated some possible
      boundary conditions of retrieval-induced forgetting. As expected, a critical
      determinant of temporary forgetting was the interval between guided retrieval
      practice and a final recall test. When these two phases were separated by 24 hr,
      retrieval-induced forgetting failed to emerge. When they occurred in the same
      testing session, however, retrieval practice prompted the inhibition of related
      items in memory (i.e., Experiment 1). A delay of 24 hr between the encoding of
      material and guided retrieval practice reduced but did not eliminate retrieval
      induced forgetting (i.e., Experiment 2). These findings are considered in the
      wider context of adaptive forgetting.

PMID- 11340925
TI  - The effect of implied orientation derived from verbal context on picture
      recognition.
AB  - Perceptual symbol systems assume an analogue relationship between a symbol and
      its referent, whereas amodal symbol systems assume an arbitrary relationship
      between a symbol and its referent. According to perceptual symbol theories, the
      complete representation of an object, called a simulation, should reflect
      physical characteristics of the object. Amodal theories, in contrast, do not make
      this prediction. We tested the hypothesis, derived from perceptual symbol
      theories, that people mentally represent the orientation of an object implied by
      a verbal description. Orientation (vertical-horizontal) was manipulated by having
      participants read a sentence that implicitly suggested a particular orientation
      for an object. Then recognition latencies to pictures of the object in each of
      the two orientations were measured. Pictures matching the orientation of the
      object implied by the sentence were responded to faster than pictures that did
      not match the orientation. This finding is interpreted as offering support for
      theories positing perceptual symbol systems.

PMID- 11340926
TI  - Seeing sets: representation by statistical properties.
AB  - Sets of similar objects are common occurrences--a crowd of people, a bunch of
      bananas, a copse of trees, a shelf of books, a line of cars. Each item in the set
      may be distinct, highly visible, and discriminable. But when we look away from
      the set, what information do we have? The current article starts to address this
      question by introducing the idea of a set representation. This idea was tested
      using two new paradigms: mean discrimination and member identification. Three
      experiments using sets of different-sized spots showed that observers know a
      set's mean quite accurately but know little about the individual items, except
      their range. Taken together, these results suggest that the visual system
      represents the overall statistical, and not individual, properties of sets.

PMID- 11340927
TI  - Implicit attitude measures: consistency, stability, and convergent validity.
AB  - In recent years, several techniques have been developed to measure implicit
      social cognition. Despite their increased use, little attention has been devoted
      to their reliability and validity. This article undertakes a direct assessment of
      the interitem consistency, stability, and convergent validity of some implicit
      attitude measures. Attitudes toward blacks and whites were measured on four
      separate occasions, each 2 weeks apart, using three relatively implicit measures
      (response-window evaluative priming, the Implicit Association Test, and the
      response-window Implicit Association Test) and one explicit measure (Modern
      Racism Scale). After correcting for interitem inconsistency with latent variable
      analyses, we found that (a) stability indices improved and (b) implicit measures
      were substantially correlated with each other, forming a single latent factor.
      The psychometric properties of response-latency implicit measures have greater
      integrity than recently suggested.

PMID- 11340928
TI  - Where is the gender in gendered language?
AB  - The purpose of these studies was to examine how women and men react and
      accommodate to gender-preferential language in e-mail messages. In Experiment 1,
      participants wrote messages to two assigned "netpals." These netpals were
      actually one of the experimenters. For each participant, one netpal used female
      preferential language and the other used male-preferential language. Analyses
      revealed that the netpals' language style, and not the participants' gender,
      predicted the language used by participants in their e-mail replies. Female and
      male participants used the gender-preferential language that matched the language
      used by their netpals. In Experiment 2, the gender labels and language styles of
      netpals were independently manipulated. As before, linguistic style had the
      greatest impact on participants' language use. These results have implications
      for how people think about gendered behavior, and highlight how gendered language
      is constructed in social interaction.

PMID- 11340929
TI  - How pleasant was your childhood? Beliefs about memory shape inferences from
      experienced difficulty of recall.
AB  - People's beliefs about how memory works can affect their inferences from
      experienced difficulty of recall. Participants were asked to recall either 4
      childhood events (experienced as an easy task) or 12 childhood events
      (experienced as a difficult task). Subsequently, they were led to believe that
      either pleasant or unpleasant periods of one's life fade from memory. When the
      recall task was difficult (12 events), participants who believed that memories
      from unpleasant periods fade away rated their childhood as less happy than
      participants who believed that memories from pleasant periods fade away. The
      opposite pattern was observed when the recall task was easy (4 events). This
      interplay of recall experiences and memory beliefs suggests that the judgmental
      impact of subjective experiences is shaped by beliefs about their meaning. It
      also suggests that the recall difficulty in clinical memory work may lead a
      person to make negative inferences about his or her childhood, provided the
      person shares the popular belief that memory represses negative information.

PMID- 11340930
TI  - Confounding the effects of delay and interference on memory distortion:
      commentary on Schmolck, Buffalo, and Squire.

PMID- 11340932
TI  - [Breast reconstruction using gluteal inferior free flaps. 34 cases in 30
      patients].
AB  - Recent evolution of breast reconstruction favorised autologous tissues, without
      prosthesis. 34 gluteal inferior free flaps have been performed in 30 patients
      aged from 33 to 72 years for immediate reconstruction (6) or secondary
      reconstruction (28), unilateral (26) or bilateral (8 flaps); after complete
      mastectomy (21 included a bilateral one), partial mastectomy (3), sub-cutaneous
      mastectomy with skin-sparing mastectomy (3 bilateral cases), radical mastectomy
      with radiolesion (2), non efficient reconstruction using prosthesis (2). The
      myocutaneous flap vascularized by gluteal inferior artery was anastomosed on
      thoracodorsal pedicle or on humeral vein. Added procedures have been
      symmetrizations (21), flap modifications (21), nipple reconstruction (20). Thirty
      three flaps presented good survey. Cosmetic results were excellent in five cases,
      good in 21 cases, middle in eight cases. Flap disadvantages were: possible
      failure of microsurgery with vessel thrombosis and flap necrosis, long operative
      time (average five hours), variable quality of the skin flap and hypoesthesia of
      the posterior area of buttock. Flap advantages were: the suffisant volume (300 to
      500 g), the simple procedure to raise the flap (after specific training) and
      discrete scar of the donor site. This flap seems to be a excellent method for
      autologous mammary versus TRAM flap or latissimus dorsi added fat flap.

PMID- 11340933
TI  - [The supramalleolar flap. Our experience in 35 cases].
AB  - The authors report 35 cases of use of the supramalleolar flap described by
      Masquelet et al. in 1988. In 27 cases, the arterial blood supply was in a mixed
      (anterograde and retrograde) fashion since the perforating branch of the peroneal
      artery was spared. In eight cases the arterial blood supply was in a retrograde
      fashion due to the location of the skin loss. As described by Valenti et al. In
      1991, the authors recommend the use of a distal subcutaneous pedicled to avoid
      skin grafting over the tendons at the distal part of the lag. In main cases of
      anterograde blood supply the superficial peroneal nerve could be spread. In 33
      cases the plastic result was assessed as satisfactory. The coverage of the weight
      bearing portion of the heel was done two times with no satisfactory result.
      Coverage of the medial malleolus area, Achilles tendon and dorsal skin of the
      foot represent the main indications and the best results. Five times, a venous
      congestion was observed with three cases of partial necrosis of the flap. The use
      of a large subcutaneous pedicle did not always prevent such venous problems,
      though this technical aspect improves the vascular reliability of the flap. The
      main local alternative is the distal pedicled sural flap that needs to divide the
      sural nerve and not allows coverage as distal as the supramalleolar flap. Except
      the distal coverage of the foot, the indications of these previous both flaps are
      similar. In case of foot coverage, the medial plantar flap based on the lateral
      plantar vascular bundle, as described by Martin et al. in 1991, is the other one
      local alternative. Free flaps are indicated for extensive skin losses, or when a
      poor distal vascularity of the leg does not allow reliability of distal pedicled
      flaps.

PMID- 11340934
TI  - [Microsurgery and esthetic considerations. Two cases of heel reconstruction].
AB  - With two case reports of heel reconstruction on female patients the authors
      report the advantages and drawbacks of the two main types of reconstruction: free
      or regional flaps. Regional flaps are technically easy and reliable but their
      aesthetic after-effects on the donor site may be disabling, specially on the leg
      of a female patient. Microsurgery is technically more difficult and presents more
      complications specially on the lower limb. However, in certain conditions, and
      with the appropriate choice of donor site, free flaps authorize good quality
      reconstructions with minimal aesthetic after-effects.

PMID- 11340935
TI  - [Terminal-lateral nerve anastomoses. Preliminary clinical report of two cases].
AB  - Nerve regeneration is based on three phenomenons of critical importance:
      neurotropism, nerve guidance and neurotrophis. These principles allow
      understanding the mechanisms of nerve suture and grafting, but also the newly
      described end-to-side nerve anastomoses. In this procedure, the distal stump of a
      severed nerve is anastomosed on the lateral side of an intact nerve, with or
      without removal of the perineurium. Authors report their beginning experience
      with this procedure (ten cases) and discuss the early results. End-to-side
      anastomosis seems to be a useful and reliable technique for clinical nerve
      repair. Even if nerve grafting remains the gold standard to bridge nerve defects,
      one has nothing to loose if a few minutes, anastomosing the severed nerve on the
      lateral side of an intact nerve, rather than doing nothing.

PMID- 11340936
TI  - [Darrier and Ferrand dermatofibrosarcomas--retrospective analysis of 81 cases
      over ten years (1983-1994)].
AB  - Progressive and recurrent dermatofibrosarcoma, described by Darier and Ferrand in
      1924, is a fibrous skin tumor with essentially local malignancy. This tumor is
      often only diagnosed after several recurrences. The authors present a
      retrospective study of eighty-one cases treated over a ten years period (1983
      1994) and a review of the literature. The treatment is surgical: wide and deep
      excision with respection of the safe subjacent aponeurotic plane. Therapeutic
      modalities are defined, with particular emphasis of the need for primary surgical
      treatment by excision, the possibility of in this case being significantly
      greater than after salvage operations. The prognostical factors are clinical
      factors such as size of the tumor, the risk of malignant evolution or the need
      for repeated excisions.

PMID- 11340937
TI  - [New approach to hand dressings in young children: the puppet dressing].
AB  - Applying a postoperative dressing on a child's hand is a very important matter,
      for it must be done rigorously and according to well established principles in
      order to be effective and inoffensive. The strictness of execution, that holds
      the surgeon's attention, makes us sometimes forget that the dressing is for a
      child who is usually anxious. First, we recall the general principles of a
      postoperative dressing adapted to young children. Then, we explain a method of
      applying a dressing in the shape of a puppet, which at first can appear to be
      funny, but seriously which is completely adapted to a young child. This
      pediatrician adaptation, that parents appreciate very much, makes the situation
      less stressful because the child finds himself in a game situation. The puppet
      dressing seems to be an advantageous modification of the traditional dressing of
      a child's hand.

PMID- 11340938
TI  - [2001, the odyssey of reconstructive microsurgery].

PMID- 11340939
TI  - [Single digit replantations in ambulatory surgery. 85 cases].
AB  - The author performed 85 ambulatory digital replantations between 1994 and 1999.
      Ages varied from 15 to 33 (average 24), with a prevalence of the male sex. The
      main mechanism of injury was guillotine (60%), followed by avulsion (40%).
      Surgical procedure lasted approximately four hours. Patients remained in the
      hospital for eight hours maximum, period in which they were closely observed.
      Patients received printed instructions about the risks of arterial and venous
      thrombosis and how they could observe it themselves. A protocol was established
      to evaluate the results. Patients were instructed to call the surgeon as soon as
      any change--mainly in color--was noticed. Based on a phone call, twenty patients
      were evaluated in the immediate postoperative period (24 initial hours) to rule
      out circulatory problems. In fifteen patients, thrombosis was noted in the
      replanted segment. Twelve of these patients (14.11%) lost the replanted digit
      completely. The loss of the replanted segment was not observed in the group of
      patients that did not call the surgeon.

PMID- 11340940
TI  - [Acute digital ischemia: a microsurgical emergency].
AB  - The authors are reporting their experience about the treatment of the acute
      finger ischemia concerning 14 patients. Twelve men and two women were concerned.
      The average age was 39 years old (18 to 65 years old). The acute finger ischemia
      was caused by emboli released by an ulnar aneurysm in nine cases and consecutive
      to an atrial fibrillation in five cases. The angiography was realized each time
      systemically in the emergency context. The medical or surgical etiological
      treatment was associated each time an emboli was found on the digital arteries. A
      microsurgical dissection of the digital collateral arteries permitted to perform
      a thrombectomy. The transversal arteriotomies were closed after collateral
      arteries were washed. The most proximal emboli were accessible to an extraction
      with a Fogarty's probe up to the superficial palmar arcade. An anticoagulant
      treatment was conducted in the early postoperative period. Considering this
      aggressive treatment, no secondary amputation was necessary up to today. The
      average follow-up was five years. This method has no indication for the chronic
      digital ischemias (diabetes, Buerger's disease) and for infectious or auto-immune
      arteriopathy.

PMID- 11340941
TI  - [Failure of upper limb macro-implantations: surgery and outcome. 11 cases].
AB  - The failure of macro-implantation of the upper limb must not be considered as the
      end of a therapeutic method, but instead as a step in the functional
      rehabilitation of the upper limb. From a group of 24 patients that have been
      operated with a macro-implantation of the upper limb, we have seen 11 patients
      for who the reimplantation had failed. We have studied the surgical procedure of
      those failures, the mid-term evolution (prosthesis and operations), and a long
      term evolution with the functional future of those patients. A surgical procedure
      with latissimus dorsi flap was necessary in six cases, in one hand to maintain a
      sufficient length of the stump for prosthesis and the other hand to preserve the
      articulation of the elbow. Nine patients on 11 were able to be "apparated" by a
      myoelectric prosthesis for the amputation below the elbow (seven cases), by
      prosthesis for the amputation above the elbow (two cases). On a long period of
      time (average time 51 months) only four patients had a permanent use of their
      prosthesis (myoelectric type). For us, the functional rehabilitation of the upper
      limb need two important elements: first a good quality of the stump with a
      sufficient length, and second an important motivation from the patient to live
      with his "new hand".

PMID- 11340942
TI  - [Secondary reconstruction of stumps above the elbow. Five cases].
AB  - The authors report a serie of five patients with five stumps above the elbow who
      needed a secondary reconstruction to allow or facilitate a prosthesis. They used
      in the first case an expansion of the latissimus dorsi flap and of the axillary
      and prepectoral region in order to free the stump of the humerus sutured on the
      thorax. In the second case, a free parascapular flap covered an unstable scar of
      the clavicula after a scapulothoracic amputation. In the third case, the transfer
      of a free flap of fibula associated with a pedicled latissimus dorsi flap had
      allowed the elongation of the stump of the humerus. In the two last cases, a
      latissimus dorsi flap pedicled in one and free in the second one had allowed to
      preserved the length of the humerus for prosthesis. The technical choices are
      eclectic and different in every case. The purpose is to obtain an efficient
      trophicity and a thickness that can support the prosthesis and if possible a
      stump long enough to improve the adaptation of the prosthesis. The five operated
      patients were able to be apparated, reducing in this way their daily functional
      difficulties.

PMID- 11340943
TI  - [Cardiovascular risk factors in essential hypertension].
AB  - Authors analysed the cardiovascular risk factors, their relationship to each
      other, the rate of multiple appearance in 1476 patients (774 men, 702 women) with
      essential hypertension. They produced a special questionnaire and risk factor
      analysing program for performing static and dynamic investigations on the base of
      international and domestic experiences. The data of their investigations
      verified, that the occurrence of obesity is very frequent and is associated with
      abnormal cholesterol and triglyceride values. The appearance of glucose
      metabolism disorder was in 44% of patients. The rate of metabolic syndrome can be
      estimated on 25-30% in the hypertensive population.

PMID- 11340944
TI  - [Effect of antigestagens on human reproduction].
AB  - A short history of antihormones is presented first. After reviewing the
      physiologic role of progesterone in the regulation of human reproduction, the
      theoretical and practical implications of suspending its actions are depicted.
      The tested or theoretically possible applications are enumerated. The initial
      success of contraceptive use of antigestagens is summarized based on their own
      research and international publications. Obstetric application is hindered by
      fear of fetal antiglucocorticoid side effects. The very remarkable success in
      termination of pregnancy is summarized by reviewing partly their own results. The
      combination of antigestagen plus prostaglandin is able to terminate pregnancies
      both in the first and second trimester very effectively (in 95% or over) and with
      very few side effects. It also renders possible the medical termination of
      unsuccessful pregnancies with diminishing complications. Although the most
      important applications take place in the regulation of human fertility, the
      initial results in the treatment of both benign (fibroids, endometriosis) and
      malignant (endometrial and ductus carcinoma) gynaecological conditions are
      encouraging. The production of mifepristone is possible in Hungary, but due to
      marketing considerations and political hurdles its registration and application
      is not considered yet.

PMID- 11340945
TI  - [Molecular biology examination in chronic lymphocytic leukemia].
AB  - Chronic lymphocytic leukaemia (CLL) is the most common adult leukaemia
      characterised by the accumulation of monoclonal CD5 + B-lymphocytes. The
      pathogenesis and the biology of CLL is complex and many details are still
      unknown. Several molecular biological methods have been used in the investigation
      of CLL, among them the study of apoptosis appears to be one of the most
      important. Initial experiences obtained by the spontaneous and fludarabine
      induced apoptosis, multidrug resistance (MDR)-test and fluorescent in situ
      hybridization (FISH) are reported by the authors. Apoptosis of CLL cells could be
      induced by fludarabine, while more studies should be performed to determine the
      exact role of MDR-test and FISH.

PMID- 11340946
TI  - [Liver diseases as risk factors in surgery. View points of internal medicine].
AB  - Morbidity and mortality risk is higher on patients suffering from liver
      disorders. Data in the literature show that elective surgery is contraindicated
      in acute hepatic illness. In case of liver enzyme elevations, an examination is
      necessary to make etiological diagnosis and assess the extent of hepatic injury.
      Risk of surgery is primarily in conjunction with patient's age, extent of liver
      and surgical disease, comorbidities and type of surgery. Among clinical and
      laboratory data even today one can most easily use the Child's classification or
      the Child-Pugh score system. In Child A patients all type of operation can be
      made, lethality is only slightly elevated. Mortality in Child B patient is 10
      30%. In Child C patients elective surgery, except transplantation, is
      contraindicated.

PMID- 11340947
TI  - [Memories about Lajos Markusovszky].

PMID- 11340948
TI  - [Urologic aspects in the work of Johannes Scultetus intitled "Armamentarium
      Chirurgicum" published in 1666].

PMID- 11340949
TI  - [Medical practice in Ferencvaros, 1887-1925. The clinical work of Drs. Jozsef
      Cseley and Marton Czoniczer].

PMID- 11340950
TI  - [Indication for surgery in sciatica. Classical article. 1950].

PMID- 11340951
TI  - [Challenge of evidence-based medicine: sense and non-sense of diagnostic tests in
      gynecology].
AB  - Evidence-based medicine is the synthesis of internal evidence (experience) and
      best external evidence (literature) aiming to solve a particular clinical
      problem. This paper gives an overview on different tools to appraise rationales
      and results of diagnostic tests such as CA-125 monitoring in patients with
      ovarian cancer.

PMID- 11340952
TI  - [Clinical experience with large-core needle biopsies of the breast and evaluation
      of histopathology].
AB  - OBJECTIVE: Interventional techniques allow a microinvasive diagnostic of breast
      lesions. We examined the reliability of large core needle biopsies for histologic
      diagnosis on breast lesions. MATERIAL AND METHODS: 143 ultrasound guided
      automated spring gun biopsies and 16 stereotactic guided vacuum-assisted device
      biopsies were analyzed. Indications included confirmation of malign or benign
      lesions and diagnosis of suspicious lesions. RESULTS: In 113 biopsies (71%) an
      invasive breast carcinoma was diagnosed, in 5 biopsies (3%) in situ/atypical
      lesions were seen and 38 cases (24%) showed benign lesions. Based on the bioptic
      results, 108 patients underwent subsequent surgery. An identical histology was
      seen in 100/108 patients (93%), 5 biopsies were false negative (5%) and 3
      specimens yielded necrotic/insufficient material. The immunohistochemical results
      of percutaneous biopsies and surgical specimens were comparable. 17 out of 113
      patients (15%) with biopsy proven carcinoma were treated with neoadjuvant
      therapy. 32/38 patients with benign lesions were follow-up clinically.
      CONCLUSION: Ultrasound- or stereotactic guided percutaneous biopsies are methods
      to confirm histological diagnosis. Based on the biopsy results the, number of
      surgical excisions can be reduced and treatment of biopsy proven carcinoma can be
      improved by individual presurgical planing.

PMID- 11340953
TI  - [Laparoscopy assisted radical vaginal hysterectomy (LAVRH) for cervical carcinoma
      -perioperative parameters and complications].
AB  - OBJECTIVE: Presently we note a standardization of techniques for laparoscopy
      assisted radical vaginal hysterectomy (LARVH). Altgassen et al. pointed to this
      fact with their evaluation of 108 operations for cervical cancer. They considered
      the necessity to perform 100 such operations before standardizing this method. In
      our survey we compare a similar number of operations performed in our department
      in order to prove whether Altgassen's thesis is correct, taking peri- and
      postoperative parameters as well as complications into consideration. For this
      purpose we analyzed the number of operations necessary to develop and standardize
      laparoscopic pelvic lymphadenectomy combined with radical vaginal hysterectomy in
      women treated for cervical cancer. PATIENTS AND METHODS: Between 1st August 1993
      and 31st January 1999, 80 patients with cervical cancer FIGO stage Ia2-IIb were
      selected for laparoscopy assisted radical vaginal hysterectomy. We were able to
      perform this operation in 71 patients. The operation reports and records of the
      postoperative period were evaluated retrospectively. RESULTS: The average
      duration of the operation increased from 380 minutes in cervix carcinoma Ia2 to
      530 minutes in cervix carcinoma IIb. The average blood loss remained the same at
      1,000 ml for each operation. Correspondingly the average decrease of hemoglobin
      was 3.5% for all operations. The number of pelvic lymph nodes removed
      unilaterally varied between 6 and 13. If the group of 37 patients with cervical
      cancer FIGO stage Ib--particularly homogenous as far as the spread of the tumor
      and the course of the operation are concerned--is divided up into one group up to
      the 50th operation and another group after the 50th operation, the regression
      analysis after the 50th operation shows a statistically significantly higher
      number of lymphnodes (11 compared to 25; Mann-Whitney-U-Test, p = 0.00014).
      However no differences were found for mean blood loss (800 ml compared to 700 ml)
      or duration of operation (400 minutes compared to 420) (Mann-Whitney-U-Test, p >
      0.05). 5% of serious complications were associated with the laparoscopic part of
      the procedure--a blood vessel lesion, a ureter lesion, two postoperative
      intraperitoneal secondary hemorrhages. 7.5% serious complications in the area of
      the bladder and the ureter were associated with the vaginal part of the
      procedure. In 6% of our procedures we observed lymphedema in the lower
      extremities. Deep Compartment Syndrome was observed in 5% of our patients and
      associated with the duration of the procedure. CONCLUSION: To implement and
      standardize our technique of laparoscopic pelvic lymphadenectomy and radical
      vaginal hysterectomy a learning phase of 50 procedures was necessary.

PMID- 11340954
TI  - [Minilaparoscopy below the left costal border with radially expanding STEP-Trocar
      System in patients with previous pelvic surgery--results of a pilot study].
AB  - As a part of a prospective study of 20 patients with previous pelvic surgery, the
      efficacy of using a 2/3 mm dilatable STEP device (InnerDyne, Inc., Sunnyvale,
      USA) for the first insertion in the area below the left costal border was tested,
      using 2 or 3.3 mm minilaparoscopes (Storz). Despite the high incidence of
      periumbilical omental and bowel adhesions (55%), no complications were observed
      in any of the 20 patients with previous pelvic surgery. Herewith could be
      confirmed that the use of a minilaparoscope in the area below the left costal
      border represents in high risk patients a safe and minimally invasive method for
      preventing or reducing the number of trocar-related injuries during first trocar
      insertion. In combination with the use of 2/3 mm disposable STEP-trocars if
      clinically required an atraumatic dilation and safe insertion of reusable 5 mm,
      10 mm or 12 mm trocars is enabled.

PMID- 11340955
TI  - [Risk of uterine rupture after cesarean section--analysis of 1,086 births].
AB  - OBJECTIVE: In the presented paper, obstetrical management after previous
      caesarian section was studied in a large patient collective at the University
      Department of Gynaecology and Obstetrics in Cologne from 1979 to 1995. Particular
      attention was given to the feared complication of rupture of the uterus.
      PATIENTS: From a total of 15,166 deliveries, 1,086 of the births had been
      preceded by one or more caesarian section. These 1,086 births formed the patient
      collective for the present study. RESULTS: Vaginal delivery was attempted in
      44.5% of patients and was successful in 86% of those cases. If there had been a
      previous caesarian section, the percentage shifted in favour of vaginal delivery.
      All patients with more than two previous caesarian sections were delivered by a
      primary caesarian section. The feared complication of rupture of the uterus
      occurred in four cases, for which case reports are presented. In view of such
      cases, signs of imminent uterus rupture often constitute an indication for
      primary (11.5%) or secondary resectioning (31.9%). No relationship was found
      between fetal outcome and mode of delivery. CONCLUSION: This retrospective study
      confirms the general recommendation of vaginal delivery following previous
      caesarian section as long as risks are minimized by a readiness to proceed with
      resectioning when signs of imminent rupture of the uterus arise.

PMID- 11340956
TI  - [Liposuction for "body contouring" in gynecology].
AB  - OBJECTIVES: The aim of this study was to describe the possible use of the
      ultrasound-assisted liposuction and liposuction with the tumescent technique for
      the contouring and remodelling of superficial fat areas of women in the field of
      gynaecology. PATIENTS AND METHODS: Between 1997 and 1999 85 healthy female
      patients underwent a liposuction in the department of gynaecology of the
      university of Essen. The patients were divided into two groups. Thirty patients
      (group 1) underwent an ultrasound-assisted liposuction whereas the remaining 55
      patients (group 2) were operated using only the tumescent technique. RESULTS:
      From the operated 582 body areas a large volume liposuction with the aspiration
      of more than 1,000 cc fat was performed in 48.2% of the cases. In the remaining
      51.8% of the cases aspiration volumes between 300 and 1,000 cc fat were obtained.
      No statistically significant differences could be observed when comparing the
      aspirat volumes between both treatment groups (p > 0.05). Serious complications
      were not observed. DISCUSSION: Our data could show, that liposuction is an
      extremely safe method for eliminating surperficial fat depots in the sense of
      body contouring in gynaecology, but that it should not be used for the reduction
      of obese body volumes. If ultrasound-assisted liposuction is really superior to
      liposuction with the tumescent technique remaining uncertain, no time gain could
      be observed due to this technique.

PMID- 11340957
TI  - [Dynamic tests of the urethral sphincter closure and pelvic floor function].
AB  - In the group of stress incontinent women (n = 54) the values of cough leak point
      pressure (CLPP) and Valsalva leak point pressure (VLPP) were studied together
      with urethral stress profiles. So as to evaluate the function of the pelvic floor
      during stress manoeuvers the electromyographic potentials were simultaneously
      recorded. It was verified, that the values of CLPP were significantly increased
      in comparison with VLPP (p < 0.01), while electromyographic potentials obtained
      by CLPP test were more powerful than those recorded by VLPP (p < 0.01-p < 0.005)
      in different subgroups. According to the results mentioned above it can be
      concluded, that the reaction of the pelvic floor differs significantly due to
      various stress manoeuvers, like coughing, Valsalva etc. These findings should be
      considered in evaluation of the type of dysfunction and of the appropriate
      surgical treatment.

PMID- 11340958
TI  - Laparoscopic management of consecutive ovarian pregnancy in a patient with
      infertility.
AB  - The diagnosis of ovarian pregnancy is based on the improper rise of serum beta
      hCG levels, sonographic findings of an empty uterus, highly characteristic
      ovarian formation with double hyperechogenic ring surrounding small hypoechogenic
      field, and the laparoscopic verification of Spiegelberg's criteria. We present a
      case of ovarian pregnancy in spontaneous cycle in 34-year-old woman following two
      unsuccessful IVF/ET procedures and ovarian pregnancy on contralateral side
      laparoscopically treated seven months ago, also achieved in non-stimulated,
      spontaneous cycle. On admission she had a serum hCG level of 596 mIU/mL on cycle
      day 46 and an empty uterus. Transvaginal sonography showed a 20 mm ring-like
      thick-walled hyperechogenic structure within the left ovary. The echogenic ring
      was surrounded by irregular, hypoechogenic structures suggestive of an ovarian
      pregnancy with periluteal hemorrhage and blood clots. The ruptured cystic ovarian
      pregnancy and the corpus luteum were removed by laparoscopy. During the procedure
      we have seen two clips on the right ovary placed laparoscopically to achieve
      hemostasis after rupture of the ovarian pregnancy seven months ago.
      Histopathology showed isolated chorionic villi within hemorrhagic areas in the
      vicinity of the corpus luteum.

PMID- 11340960
TI  - Idiocy and the law in colonial New England.
AB  - A review of the laws and records of the courts of colonial New England indicate
      some ways the early settlers thought about and responded to idiocy. Early
      Massachusetts laws extended certain rights to idiots: They authorized the
      transfer of property, exonerated idiots who committed capital crimes, and
      extended relief to idiots who were impoverished. There is no documentation of the
      implementation of these laws nor is there direct reference to idiocy in court
      proceedings. Nevertheless, the court records identify certain individuals with
      incompetence and atypical behavior suggestive of idiocy. Most of the colonial
      laws as well as the colonists' ways of thinking about idiocy originated in
      English common law and custom. The New England colonial laws and records of the
      courts offer insights into contemporary issues regarding mental retardation.

PMID- 11340959
TI  - [Two case reports of long-term treatment of endometriosis with cyproterone
      acetate].
AB  - Endometriosis is a benign, chronic disease with high incidence during the female
      fertile period. Conservative treatment is dominated by the use of GnRH-analog
      substances, Gestagens and Danazol. As a case report we present the signs and
      symptoms, as well as the long term therapeutical strategy in two cases of severe
      endometriosis. Combined with signs of hyperandrogenism, the long term use of
      cyproteroneacetate is beneficial.

PMID- 11340961
TI  - Personal characteristics and contextual factors associated with residential
      expenditures for individuals with mental retardation.
AB  - A multivariate analysis was done to determine the relative importance of
      facility, resident, and community characteristics to expenditures. Facility
      factors associated with higher expenditures included ownership, facility size,
      facility services, and location. Individuals with a greater number of activity of
      daily living limitations, developmental disabilities, and more severe levels of
      mental retardation had higher expenses. Findings could improve our understanding
      of the costs of long-term residential care, assisting us to economically and
      effectively bring this population into the community. Data used are from the 1987
      National Medical Expenditure Survey Institutional Population Component.

PMID- 11340962
TI  - Ethical challenges in the conduct of research involving persons with mental
      retardation.
AB  - Researchers face challenges in balancing the demands of sound research methods
      and ethical standards in studies involving persons with mental retardation. While
      the autonomy of individuals must be respected, researchers also have an ethical
      responsibility to protect vulnerable individuals from social, psychological, or
      physical risks of research participation. Some individuals may face significant
      barriers in the research decision-making process due to cognitive limitations,
      lack of information and support, and limited experience and opportunities for
      exercising choice. The historical context of biomedical and behavioral research
      involving persons with mental retardation and current ethical issues related to
      informed consent and surrogate decision-making are examined. Implications for
      researchers and professionals are discussed, including ways to support
      individuals with mental retardation and their families in research decision
      making.

PMID- 11340963
TI  - "Me? I'm not a drooler. I'm the assistant": is it time to abandon mental
      retardation as a classification?

PMID- 11340964
TI  - Images of idiocy in Puritan New England.

PMID- 11340965
TI  - Everyone is beautiful.

PMID- 11340966
TI  - Making moral decisions: comparing two theories.

PMID- 11340967
TI  - The Human Genome Project and eugenics: identifying the impact on individuals with
      mental retardation.

PMID- 11340968
TI  - Consumer and surrogate preferences for a cash option versus traditional services:
      Florida adults with developmental disabilities.
AB  - As long-term service expenditures have risen, policymakers have sought ways to
      control costs while maintaining consumer satisfaction. Concurrently, there is
      increasing interest in the disability community in consumer direction. The Cash
      and Counseling Demonstration and Evaluation (CCDE) seeks to increase consumer
      direction and control costs by offering a cash allowance and information services
      to persons with disabilities, enabling them to purchase needed assistance.
      Because the disability community is composed of diverse subgroups, needs of these
      consumer communities must be assessed individually. Results from a telephone
      survey conducted to assess the interest in a cash option for Florida adults with
      developmental disabilities is presented, the three-state CCDE described, how
      survey findings can inform consumer information efforts discussed, and policy
      issues highlighted.

PMID- 11340969
TI  - Determination of acetonitrile and ethanol in water by guided microwave
      spectroscopy with multivariate calibration.
AB  - The feasibility of using guided microwave spectroscopy (GMS) utilizing the
      frequency range 0.25-3.20 GHz, was combined with multivariate calibration for the
      determination of acetonitrile or ethanol concentration in water. A wide range of
      different concentrations was used (up to 30% v/v). Partial least squares (PLS)
      and weighted ridge regression (WRR) was applied to generate a model for
      prediction, based upon the microwave spectra. A high level of collinearity was
      observed in both of the sample data sets and this was reduced by background
      subtraction. The prediction ability for the two types of regression models were
      found to be comparable with the percentage error of prediction (PEP) being
      approximately 2.5% for the acetonitrile samples and 1.1% for ethanol samples.

PMID- 11340970
TI  - New isoelectric buffers for capillary electrophoresis: N-carboxymethylated
      polyethyleneimine as a macromolecular isoelectric buffer.
AB  - Isoelectric buffers are attractive for electrophoresis because of their low
      conductivity, and their compatibility with indirect photometric detection in
      capillary electrophoresis (CE) where they do not interfere with the detection by
      exhibiting competitive displacement of the UV-absorbing probe ion. N
      carboxymethylated polyethyleneimine (CMPEI) was prepared by introducing a half
      molar equivalent of carboxylate groups onto a polyethyleneimine backbone. Its
      isoelectric point determined by conductometric titration and from the pH of its
      dilute aqueous solution is approx. 6.8, which allows isoelectric buffering at a
      lower pH compared to histidine (pI7.7). Although the isoelectric point is
      somewhat diffuse, as expected for a polymeric compound, it exhibits a buffering
      capacity at a pI point of about twice that of histidine. Studies of
      electroosmotic flow (EOF) profile at various pH values in fused silica
      capillaries showed that CMPEI adsorbs onto the fused silica wall and reverses the
      EOF at pH < 6.5. CMPEI was applied as a buffer in an electrolyte containing 0.5
      mM of the anionic dye tartrazine used as the probe for indirect detection of
      anions. The separation system exhibited a stable baseline, no system peaks,
      separation efficiencies of up to 195,000 theoretical plates, and detection limits
      down to 0.2 microM or 2 amol of injected analyte.

PMID- 11340971
TI  - A quartz crystal resonant sensor (QCRS) study of HSA--drug interactions.
AB  - Human serum albumin (HSA) was immobilised on the gold surface of a quartz crystal
      resonance sensor (QCRS) and exposed to warfarin and diazepam. Distinct decreases
      in frequency of differing magnitudes were observed upon exposure of the protein
      to each of the compounds suggesting strongly that a ligand interaction was
      occurring. Moreover, as sequential exposure in any order was observed to yield
      distinct repeatable frequency decreases for the ligands indicated, screening for
      site specific binding may be possible. Identically immobilised bovine serum
      albumin (BSA) gave no response to either compound.

PMID- 11340972
TI  - Microchip separations of transition metal ions via LED absorbance detection of
      their PAR complexes.
AB  - Micellar electrokinetic chromatography was utilized in the electrophoretic
      separation of seven transition metal ions, colorimetrically complexed by 4-(2
      pyridylazo)resorcinol (PAR) on a glass capillary electrophoresis microchip.
      Detection of the PAR metal chelates was demonstrated using a green light emitting
      diode (540 nm) and a miniature photomultiplier tube. Parameters investigated
      included the effect of buffer type, pH and surfactant concentration (sodium
      dodecyl sulfate, SDS) on the separation efficiency. The optimally determined
      background electrolyte contained 10 mM ammonium phosphate buffer (pH 7.5), 1 mM
      PAR to prevent kinetic lability problems and 75 mM SDS for enhanced resolution.
      The separation of seven transition metal ions, Co2+, V3+, Ni2+, Cu2+, Fe2+, Mn2+
      and Cd2+, was achievable in under 65 s, with the resolution of each metal ion in
      excess of 1.60. Detection limits obtained ranged from 400 ppb for Ni2+ to 1.2 ppm
      for Mn2+.

PMID- 11340973
TI  - Determination of metal cations on miniaturised planar polymeric separation
      devices using isotachophoresis with integrated conductivity detection.
AB  - The feasibility of using miniaturised planar polymeric separation devices for the
      isotachophoretic separation of metal cations was demonstrated. Devices were
      produced in silicone rubber using a cast moulding fabrication technique.
      Detection was performed using an integrated single electrode conductivity
      detector, a design which offers simple fabrication and high resolution. The
      electrical characteristics of the devices were found to be suitable for
      performing electroseparations with a power dissipation of up to 1.5 W m-1 being
      achieved. The separation of a sample containing a mixture of the four metal ions
      lithium, lanthanum, dysprosium and ytterbium was reproducibly achieved using
      miniaturised devices. A comparison with a capillary scale separation of the same
      mixture was made. The miniaturised separations were achieved in under 600 s,
      which is less than half the time taken for the capillary scale separations.

PMID- 11340974
TI  - Enantioselective separation of epoxides by capillary electrophoresis employing
      sulfated beta-cyclodextrin as chiral selector.
AB  - A capillary electrophoresis method was developed for the enantioseparation of
      epoxide compounds. Sulfated beta-cyclodextrin was employed as a chiral selector.
      Phosphate-triethanolamine buffer showed a chiral separation effect when employing
      charged sulfated beta-cyclodextrin. The effect of pH, triethanolamine
      concentration and sulfated beta-cyclodextrin concentration on the resolution was
      studied. Methanol was tested as an organic modifier. Several other epoxides were
      successfully separated by the proposed method.

PMID- 11340975
TI  - On-column amperometric detection of ofloxacin and pasiniazid in urine by
      capillary electrophoresis with an improved fractured joint and small detection
      cell.
AB  - An improved high-voltage electric field isolating joint and small detection cell
      have been carefully designed and fabricated. The joint possesses short steady
      time, high electric conductance efficiency and high performance. The cell is
      convenient to install and remove the capillaries with and without the joint, as
      well as to fix, adjust and insert the microelectrode into the detection
      capillary. Using the joint and the cell, an analytical method for determination
      of ofloxacin (Oflx) and pasiniazid (Ipa) in urine by capillary electrophoresis
      with on-column amperometric detection was developed. The calibration lines were
      linear in the range of 10-100 mg l-1 of Oflx and 1.0-50 mg l-1 of Ipa,
      respectively. The detection limits were 8.5 mg l-1 of Oflx and 0.80 mg l-1 of
      Ipa. Their recovery ranged from 101 to 104%. The accuracy and intra-day and inter
      day reproducibility of Oflx and Ipa were determined with satisfactory results.
      This method was successfully used for determining Oflx and Ipa in human urine.

PMID- 11340976
TI  - Fluorescence quenching high-performance thin-layer chromatographic analysis
      utilizing a scientifically operated charge-coupled device detector.
AB  - A scientifically operated charge-coupled device detector combined with
      fluorescence quenching high-performance thin-layer chromatographic plates was
      employed for the detection of organic compounds, The plates were excited with 254
      nm light from a mercury lamp, and quantitative information was obtained from
      organic compounds that absorbed the optimum conditions for detection. The linear
      dynamic range, sensitivity, and reproducibility of the system were evaluated by
      quantitative analysis of famotidine, acetaminophen, caffeine, and acetylsalicylic
      acid. The detection limits of the system were found to be in the nanogram range.

PMID- 11340977
TI  - Fast sequential injection determination of benzo[A]pyrene using variable angle
      fluorescence with on-line solid-phase extraction.
AB  - A methodology for the analysis of drinking water for one of the most potent
      carcinogenic agents known; benzo[a]pyrene (BaP), in the presence of other
      interfering PAHs is presented. The methodology described is based on the
      sequential injection analysis of the sample on to a microcolumn (containing 5 mg
      of C18) where extraction and preconcentration of BaP takes place, followed by
      elution of BaP with 1 ml of 1,4-dioxane and subsequent detection by using
      variable angle fluorescence. The advantages of the method include the small
      amount of stationary phase employed together with the possibility of re-using the
      phase in order to carry out a large number of injections without the need for
      column re-packing. Also noteworthy is the small volume of 1,4-dioxane used to
      elute the BaP retained on the column and the small sample volumes required (9-10
      ml) for achieving detection limits at the ng l-1 level. Thus, a methodology for
      BaP determination is obtained which complies with the requirements of the
      98/83/EC Directive which fixes a maximum admissible concentration for this
      pollutant in waters for public consumption of 10 ng l-1. The variable angle
      spectra obtained are further processed by means of the multiple linear regression
      technique. The detection limit for BaP is 2.5 ng l-1, and the linear range is
      between 7.5 and 280 ng l-1.

PMID- 11340978
TI  - Chromatographic analysis of phenethylamine-antihistamine combinations using C8,
      C18 or cyano columns and micellar sodium dodecyl sulfate-pentanol mixtures.
AB  - The chromatographic behaviour of binary and ternary mixtures of several
      phenethylamines (phenylephrine, phenylpropanolamine, ephedrine, pseudoephedrine
      and methoxyphenamine) and antihistamines (pheniramine, carbinoxamine, doxylamine,
      chlorpheniramine, dexchlorpheniramine, dexbrompheniramine, diphenhydramine,
      tripolidine, azatadine and phenyltoloxamine), found in cough-cold pharmaceutical
      preparations, was studied using C8, C18 and cyano columns, micellar mobile phases
      of sodium dodecyl sulfate (SDS) and pentanol and UV detection. Using a C8 column
      and mobile phases of 0.05 mol l-1 SDS-6% v/v pentanol or 0.15 mol l-1 SDS-2% v/v
      pentanol at pH 7, more than 30 different phenethylamine-antihistamine
      combinations can be resolved in < 15 min. Intra- and inter-day repeatabilities
      and reproducibilities evaluated at three different drug concentrations (0.5, 5
      and 25 micrograms ml-1, n = 10) were below 1.6, 2.5 and 2.4%, respectively. The
      drug amounts found in 18 formulations agreed with those declared by the
      manufacturers within the tolerance limits, and with those obtained using a mobile
      phase of 55% v/v methanol at pH 7. No interference was observed from other
      accompanying drugs such as acetylsalicylic acid, ascorbic acid, betamethasone,
      bromhexine, caffeine, codeine, dextromethorphan, paracetamol, prednisolone,
      salicylamide and tartrazine. The proposed procedure has the advantage over the
      conventional aqueous-organic procedure of using a small amount of organic
      solvent, which is highly retained in the SDS solution. The efficiencies are also
      greater. On the other hand, in the micellar system, the retentions of
      phenethylamines and antihistamines are similar, although the compounds can be
      easily resolved. In contrast, using the methanol-water mobile phase, the
      phenethylamines are weakly retained, whereas the antihistamines usually show a
      high retention.

PMID- 11340979
TI  - Characteristics of a column suitable for capacity gradient chromatography with a
      borate eluent.
AB  - In capacity gradient elution, the gradient separation of ionic species is
      achieved by decreasing the ion-exchange capacity of a column during the course of
      the separation. Diol-type hydroxy groups on the resin surface form anionic
      complexes with borate as an eluting reagent. Thus, a chemically bonded anion
      exchange column enriched with residual hydroxy groups allows the creation of a
      capacity gradient. An increase in the amount of the complex formed gradually
      brings about a decrease in the ion-exchange capacity of the column, and strongly
      bound analyte ions are eluted. We investigated the characteristics of a column
      suitable for this eluent system. The concentration of borate eluent required to
      remove the ion-exchange capacity depended inversely on the ratio of the residual
      hydroxy groups to functional groups. On a column in which this ratio was
      approximately 100, the ion-exchange capacity could easily be adjusted by using a
      low concentration of mannitol as a competing reagent. Use of this column led to
      very small baseline shifts during the borate-mannitol gradients, and to the
      simultaneous determination of anions with widely varying retention times.

PMID- 11340980
TI  - Headspace gas chromatographic determination of 2-alkyl-5,5-dimethyl-1,3-dioxane
      derivatives in wastewaters of a polyester resin plant.
AB  - The static headspace gas chromatographic technique can be conveniently employed
      to check the presence and amount of the odorous side-products, 2-R-1,3-dioxanes
      (R = H, CH3, C2H5, i-C3H7, n-C3H7), directly from the wastewaters flowing from
      the reactors during the synthesis of polyester resins. By the optimisation of a
      simple and direct analytical method, the amounts of these compounds may be
      continuously monitored and controlled. This method is characterized by good
      repeatability (3-4%) and does not seem to suffer from matrix effects. The
      detection limits for the determination of the five dioxanes fall in the range 400
      700 micrograms dm-3 (alpha = beta = 0.05).

PMID- 11340981
TI  - Determination of aliphatic alcohols, squalene, alpha-tocopherol and sterols in
      olive oils: direct method involving gas chromatography of the unsaponifiable
      fraction following silylation.
AB  - In general, analyses for aliphatic alcohols, sterols and tocopherols in vegetable
      oils are performed separately. A simple and reliable procedure is presented for
      the quantification of the alkanols, squalene, alpha-tocopherol and sterols in
      olive oils by a direct method involving gas chromatographic (GC) analysis of the
      unsaponifiable fraction after silylation. The method eliminates the need for a
      preliminary thin-layer chromatographic (TLC) fractionation prior to GC. External
      standard calibration with reference substances was used for the quantification of
      squalene, alpha-tocopherol and sterols and internal standard calibration for the
      quantification of aliphatic alcohols. The analyte recovery and the repeatability
      of the quantitative results were evaluated and were acceptable for routine use.

PMID- 11340982
TI  - Exposure to 4,4'-methylenediphenyl diisocyanate (MDI) during moulding of rigid
      polyurethane foam: determination of airborne MDI and urinary 4,4'
      methylenedianiline (MDA).
AB  - Occupational exposure to 4,4'-methylenediphenyl diisocyanate (MDI) was measured
      during moulding of rigid polyurethane foam. The aim of the study was to find out
      whether an MDI-derived urinary amine metabolite could be detected in the urine of
      workers exposed to apparently low levels of MDI. Airborne MDI was sampled on 1-(2
      methoxyphenyl)-piperazine (2MP)-impregnated glass fibre filters and determined by
      high-performance liquid chromatography (HPLC) using ultraviolet (UV) and
      electrochemical (EC) detection. The limit of detection of MDI was 3 ng ml-1 for a
      20 microliters injection. The precision of sample preparation, expressed as
      relative standard deviation (RSD), was 1.3% with UV detection and 2.1% with EC
      detection at a concentration of 70 ng MDI ml-1 (n = 6). The 2MP-MDI derivative
      was stable at +4 degrees C up to eight weeks. The accuracy of the method was
      validated in an international quality control programme. Workers (n = 57) from
      three different factories participated in the study. Urinary 4,4'
      methylenedianiline (MDA) metabolite was determined after acid hydrolysis as
      heptafluorobutyric anhydride derivatives by gas chromatography-mass spectrometry
      using chemical ionisation and monitoring negative ions. The limit of detection in
      urine was 0.2 nmol l-1. The precision of six analyses for a urine sample spiked
      to a concentration of 1 nmol l-1 was 29% (RSD). The MDI concentrations were below
      the limit of detection in most (64%) of the air samples collected in the worker's
      breathing zone. Still, detectable amounts of MDA were found in 97% of the urine
      samples. Monitoring of urinary MDA appears to be an appropriate method of
      assessing MDI exposure in work environments with low or undetectable MDI
      concentrations in the workplace air.

PMID- 11340983
TI  - Determination of diphenylamine stabilizer and its nitrated derivatives in
      smokeless gunpowder using a tandem MS method.
AB  - A novel method for determination of diphenylamine (DPA) and its nitrated
      derivatives, which are considered as characteristic components in smokeless
      powder and gunshot residues, is described. A tandem mass spectrometric method is
      established and mass spectrometer parameters optimized for each compound to
      obtain higher sensitivity. Under optimum conditions, quantitative analysis was
      carried out. The linear ranges are 5.0-200.0, 2.0-200.0 and 5.0-250.0 ng ml-1 and
      the detection limits are 1.0, 0.5 and 2.5 ng ml-1 for diphenylamine (DPA), N-NO
      diphenylamine (N-NO-DPA) and 4-NO2-diphenylamine (4-NO2-DPA), respectively. Intra
      assay and inter-assay precision and accuracy of analysis of these three samples
      were investigated. Based on the regression lines obtained above, smokeless
      samples were analyzed. It was found that there are 0.952% DPA, 0.384% N-NO-DPA
      and 0.128% 4-NO2-DPA in smokeless powder. Recovery tests showed that using cotton
      swabs, 80.3 +/- 4.9% DPA, 79.6 +/- 3.1% N-NO-DPA and 83.1 +/- 5.4% 4-NO2-DPA
      could be recovered from human hands.

PMID- 11340984
TI  - High surface density immobilization of oligonucleotide on silicon.
AB  - Oligonucleotide (11-mer) molecules are immobilized on silicon in high surface
      population using either a permanent thioether bond or a chemo-selectively
      reversible disulfide bond to the surface thiol functionality. Substrate hydroxy
      groups are first silanized with an 11 carbon trichlorosilane containing a
      terminal, protected thiol moiety. Oligonucleotide modified with a tether
      possessing a terminal thiol group is further derivatized with a water-soluble,
      halobenzylic bifunctional reagent, which allows the complete conjugate to be
      attached to the surface through a permanent thioether bond. Alternatively, the
      oligonucleotide-tether complex can be combined with a pyridyldisulfide compound,
      which, in turn, facilitates the formation of a reversible disulfide bond with
      surface thiol. The amount of immobilized oligonucleotide was determined by
      radiochemical labeling with 32P. Additional verification of surface amounts was
      obtained from X-ray photoelectron spectroscopic analysis of substrates. The
      results of the immobilization protocols are compared with the oligonucleotide
      surface population achieved through the conventional silanizing agent,
      mercaptopropyltrimethoxysilane. Finally, a preliminary confirmation of duplex
      formation of a TTU-attached 25-mer with its complementary strand is outlined.

PMID- 11340985
TI  - The preparation, solubilisation and binding characteristics of a beta 2
      adrenoceptor isolated from transfected Chinese hamster cells.
AB  - beta 2-Adrenoceptor agonists (beta-agonists) are well known for their growth
      promoting and repartitioning effects in many species. Although the use of these
      compounds to increase muscle mass in stockfarming is prohibited within the EU,
      under directive 96/22/EC, significant illegal use still occurs. With legal and
      illegal synthesis of new structurally related compounds, the detection of
      traditional beta-agonists and new derivatives becomes increasingly problematical.
      This method describes the isolation and solubilisation of a beta 2-adrenoceptor
      from a transfected Chinese hamster ovary cell line, using the detergent
      digitonin. The solubilised receptor retained its activity and was isolated from
      the cell membrane at a concentration of 550 +/- 100 fmol mg-1 of solubilised
      protein. Competition analysis using the tritiated antagonist dihydroalprenolol
      revealed receptor affinity for five structurally different beta-agonists, with
      IC50 values ranging from 2.1 +/- 0.76 x 10(-7) M for salmeterol to 1.1 +/- 0.62 x
      10(-5) M for ractopamine. This study has demonstrated that transfected cell lines
      with a high expression of beta 2-adrenoceptors are a convenient source of active
      receptor material. Solubilised beta 2-adrenoceptors could form the basis of a
      multi-analyte screening assay for use in routine screening.

PMID- 11340986
TI  - Multimembrane carbon fiber microelectrodes for amperometric determination of
      serotonin in human urine.
AB  - An electrochemical sensor for the determination of serotonin in urine was
      prepared using Ni(II)-phthalocyanine and Nafion to modify the surface of a 4 mm
      length carbon fiber microelectrode. The resultant sensor was found to improve the
      response towards this neuronal amine versus the microelectrode without the
      polymer films. Different polymerization conditions, as well as different
      conditioning solutions and buffer systems, were investigated in order to optimize
      the response of the electrodes. Square wave voltammetry (SWV) is proposed as a
      direct method for determination of serotonin in human urine, after a solid-liquid
      extraction process. The proposed method enables a detection limit for serotonin
      of 0.80 +/- 0.04 microgram L-1 to be achieved at a reduction potential of 0.35 V,
      with an overall prediction error of 2.2% and recoveries of 93%.

PMID- 11340987
TI  - Response mechanism of a neutral carrier Hg(II) polymeric membrane ion-selective
      electrode. SEM and EDAX study.
AB  - Scanning electron microscopy (SEM) and energy dispersive atomic X-ray
      spectrometry (EDAX) were used to study the response mechanism of a previously
      reported new Hg membrane ion-selective electrode (ISE) based on 1,3
      diphenylthiourea. These techniques allowed the study of the membrane surface
      characteristics, such as the morphological homogeneity and chemical composition.
      A 'twice Nernstian' response at pH > or = 7 was explained by the detection of the
      Hg(OH)+ cation. A normal Nernstian response was found at acidic pH values. Using
      these techniques, both coordination compounds, [Ligand-Hg-OH] at pH 7 and [Ligand
      Hg-Ligand] at pH 4.5, were confirmed on the electrode membrane surface activated
      with Hg(NO3)2 solution at both pH values. These methods provide results which are
      independent of the potential measurement data and in agreement with them. A
      successful response model has explained both independent and unbiased sets of
      results. These conclusions confirm the proposed response mechanisms for this new
      Hg membrane sensor.

PMID- 11340988
TI  - Silver(I) ion-selective membrane based on Schiff base-p-tert-butylcalix[4]arene.
AB  - A PVC membrane electrode for silver(I) ion based on Schiff base-p-tert
      butylcalix[4]arene is reported. The electrode works well over a wide range of
      concentration (1.0 x 10(-5)-1.0 x 10(-1) mol dm-3) with a Nernstian slope of 59.7
      mV per decade. The electrode shows a fast response time of 20 s and operates in
      the pH range 1.0-5.6. The sensor can be used for more than 6 months without any
      divergence in the potential. The selectivity of the electrode was studied and it
      was found that the electrode exhibits good selectivity for silver ion over some
      alkali, alkaline earth and transition metal ions. The silver ion-selective
      electrode was used as an indicator electrode for the potentiometric titration of
      silver ion in solution using a standard solution of sodium chloride; a sharp
      potential change occurs at the end-point. The applicability of the sensor to
      silver(I) ion measurement in water samples spiked with silver nitrate is
      illustrated.

PMID- 11340989
TI  - Spectroelectrochemical study of the oxidative doping of
      polydialkylphenyleneethynylene using iterative target transformation factor
      analysis.
AB  - Iterative target transformation factor analysis (ITTFA) was used to determine the
      spectra of the individual species generated during the oxidative p-doping of
      films of poly(para-phenyleneethynylene) (PPE). UV-visible spectra of PPE films on
      transparent electrodes were obtained in-situ during an anodic sweep. ITTFA
      identified 4 species present during the oxidation, which we assign as neutral
      polymer, polaron species, bipolaron species, and a species formed by further
      bipolaron reaction. The region of electrochemical stability for each of these
      species was identified and their potential-dependent profiles were obtained. This
      work is the first deconvolution of conjugated polymer spectroelectrochemistry.

PMID- 11340990
TI  - Determination of nucleic acids with crystal violet by a resonance light
      scattering technique.
AB  - For the first time, Crystal Violet (CV) was used to determine nucleic acid
      concentrations using the resonance light-scattering (RLS) technique. Based on the
      enhancement of the RLS of CV by nucleic acids, a new quantitative determination
      method for nucleic acids in aqueous solutions has been developed. At pH 5.03 and
      ionic strength 0.005 mol kg-1, the interaction of CV with nucleic acids results
      in three characteristic RLS peaks at 344.0, 483.0 and 666.0 nm. With 4.0 x 10(-5)
      mol l-1 of CV, linear relationships were found between the enhanced intensity of
      RLS at 666.0 nm and the concentration of nucleic acids in the range 0-2.5
      micrograms ml-1 for herring sperm DNA, 0-4.0 micrograms ml-1 for calf thymus DNA
      and 0-4.5 micrograms ml-1 for yeast RNA. The limits of determination were 13.8 ng
      ml-1 for herring sperm DNA, 36.8 ng ml-1 for calf thymus DNA and 69.0 ng ml-1 for
      yeast RNA. The assay is convenient, rapid, inexpensive and simple.

PMID- 11340991
TI  - Determination of nucleic acids based on shifting the association equilibrium
      between tetrasulfonated aluminium phthalocyanine and acridine orange.
AB  - Based on the ability of nucleic acids to shift the association equilibrium of the
      ion-association complex of Acridine Orange and tetrasulfonated aluminium
      phthalocyanine, thus leading to an increase in the phthalocyanine fluorescence, a
      method is suggested for the fluorimetric determination of nucleic acids.
      Investigations were carried out on the spectral characteristics, order of
      addition of reagents, selection of the buffer system, effect of pH, influence of
      reaction time, effect of salt, the usage of reagents, interference of foreign
      substances and the effect of different acridine derivatives. Under the optimum
      conditions, the calibration graphs for the determination of calf thymus DNA (CT
      DNA), salmon DNA (SM DNA) and yeast RNA were linear over the ranges 0.04-1.2,
      0.04-1.2 and 0.1-1.2 micrograms cm-1, respectively. The detection limits for CT
      DNA, SM DNA and RNA were 17, 24 and 98 micrograms cm-3, respectively. The
      relative standard deviation (n = 6) was within 4.6% for the detection of samples.
      The method was applied to the determination of Staphylococcus aureus DNA and the
      result was in agreement with that achieved by a UV method.

PMID- 11340992
TI  - A new red-region substrate, tetra-substituted amino aluminium phthalocyanine, for
      the fluorimetric determination of H2O2 catalyzed by mimetic peroxidases.
AB  - A new red-region fluorogenic substrate, tetra-substituted amino aluminium
      pthalocyanine, was developed for the selective determination of H2O2 based on the
      catalytic effect of mimetic peroxidases, viz., hemin or iron
      tetrasulfonatophthalocyanine (FeTSPc). Under the optimum conditions, the
      linearity of the calibration graph for the determination of H2O2 with hemin (or
      FeTSPc) as the catalyst was in the range from 0.0 to 3.0 x 10(-7) mol L-1 (or
      from 0.0 to 2.0 x 10(-6) mol L-1). The detection limits were 3.7 x 10(-9) and 4.9
      x 10(-9) mol L-1 H2O2, respectively. The relative standard deviation (n = 7) was
      within 1.5% in the middle of the linear range. The peroxidase activity of the
      mimetic enzymes hemin and FeTSPc, the effects of some experimental conditions and
      the influence of foreign substances were investigated. With this substrate, 0.0
      7.5 x 10(-8) mol L-1 hemin and 0.0-2.0 x 10(-6) mol L-1 FeTSPc can be determined
      with an accuracy and precision of about 1.3%. The potential application of the
      reagent was tested by the determination of H2O2 in rainwater.

PMID- 11340993
TI  - Study of the spectrophotometric analysis of protein solution with p
      iodochlorophosphonazo as adsorbate by the microphase adsorption-spectral
      correction technique.
AB  - A microphase adsorption-spectral correction (MPASC) technique was established,
      which consists of Langmuir adsorption and the spectral correction technique. The
      hypothesis of a microelectric field formed in macromolecules is proposed, the
      existence of which results in the adsorption and aggregation of dye molecules in
      macromolecules. This paper describes the spectrophotometric analysis of protein
      solution with p-iodochlorophosphonazo (p-ICPA) dye. The results showed that the
      adsorption ratios of p-ICPA to proteins (bovine serum albumin, ovalbumin,
      myoglobin and gamma-globulin) at pH 2.56 were 54, 25, 14 and 90, respectively,
      their adsorption constants 2.86 x 10(5), 1.42 x 10(6), 2.38 x 10(5) and 1.09 x
      10(5) and their absorptivities 8.00 x 10(5), 4.02 x 10(5), 1.77 x 10(5) and 1.15
      x 10(6) l mol-1 cm-1 at 620 nm. The analysis of practical samples showed that the
      recovery of protein was between 92.3 and 108% and the relative standard deviation
      was 4.7%.

PMID- 11340994
TI  - Determination of manganese in water samples by flame atomic absorption
      spectrometry after cloud point extraction.
AB  - Cloud point extraction has been used for the preconcentration of manganese, after
      the formation of a complex with 1-(2-thiazolylazo)-2-naphthol (TAN), and later
      analysis by flame atomic absorption spectrometry using
      octylphenoxypolyethoxyethanol (Triton X-114) as surfactant. The chemical
      variables affecting the separation phase and the viscosity affecting the
      detection process were optimized. Under the optimum conditions (i.e., pH = 9.2,
      [TAN] = 2.0 x 10(-5) mol l-1, [Triton X-114] = 0.05%, added methanol volume = 0.2
      ml), preconcentration of 50 ml of sample solution permitted the detection of 0.28
      ppb for manganese. The enhancement factor was 57.6. The proposed method has been
      applied to the determination of manganese in water samples.

PMID- 11340995
TI  - Analysis of single polymer beads for solid phase combinatorial synthesis: the
      determination of reactive thiol and within batch polydispersity of bead loadings.
AB  - Polymer beads are the starting point of many synthetic protocols, and in a number
      of combinatorial syntheses such studies are based on single beads. It has
      therefore become important that individual beads carry the same functional group
      activity and quality control of populations of beads requires a knowledge of the
      distribution of activity between the individual beads. A procedure was developed
      for the measurement of the thiol loading of single copolymer beads which is based
      on the bleaching of Michler's hydrol [4,4'-bis(dimethylamino)-diphenylcarbinol
      (BDC-OH)]. Flow injection colorimetry permits the small volumes of solution
      generated from single beads to be measured with rapid turnover and with a
      reproducibility of ca. 2%. The solution detection limit of 0.17 mM corresponds to
      a bead thiol concentration of 0.33 mmol g-1. The procedure and the variability of
      a bead population were demonstrated using modified styrene-divinylbenzene
      copolymer beads. The apparatus allowed fast, simple and accurate determinations
      to be carried out on the individual polymer beads. Within a single batch of thiol
      modified styrene-divinylbenzene beads thiol loadings ranged from < 0.35 to 2.07
      mmol g-1 or 0.12 to 1.3 mumol per bead. Polydispersity may therefore
      significantly influence screening decisions based on single bead syntheses.

PMID- 11340996
TI  - The scientific process and Hollywood: the case of hexavalent chromium.

PMID- 11340997
TI  - Effect of heterogeneity on radionuclide retardation in the alluvial aquifer near
      Yucca Mountain, Nevada.
AB  - The U.S. Department of Energy is currently studying Yucca Mountain, Nevada, as a
      potential site for a geological high-level waste repository. In the current
      conceptual models of radionuclide transport at Yucca Mountain, part of the
      transport path to pumping locations would be through an alluvial aquifer.
      Interactions with minerals in the alluvium are expected to retard the downstream
      migration of radionuclides, thereby delaying arrival times and reducing ground
      water concentrations. We evaluate the effectiveness of the alluvial aquifer as a
      transport barrier using the stochastic Lagrangian framework. A transport model is
      developed to account for physical and chemical heterogeneities and rate-limited
      mass transfer between mobile and immobile zones. The latter process is caused by
      small-scale heterogeneity and is thought to control the macroscopic-scale
      retardation in some field experiments. A geostatistical model for the spatially
      varying sorption parameters is developed from a site-specific database created
      from hydrochemical measurements and a calibrated modeling approach (Turner and
      Pabalan 1999). Transport of neptunium is considered as an example. The results
      are sensitive to the rate of transfer between mobile and immobile zones, and to
      spatial variability in the hydraulic conductivity. Chemical heterogeneity has
      only a small effect, as does correlation between hydraulic conductivity and the
      neptunium distribution coefficient. These results illustrate how general
      sensitivities can be explored with modest effort within the Lagrangian framework.
      Such studies complement and guide the application of more detailed numerical
      simulations.

PMID- 11340998
TI  - A model of cells as practical approach to simulate spring flow in the Itxina
      karstic aquifer, Basque Country, Spain.
AB  - The aim of this study is to apply a parsimonious hydrologic model to the Itxina
      karstic aquifer that can predict changes in discharge resulting from variable
      inputs (recharge). The Itxina Aquifer was divided into four cells corresponding
      to different recharge areas. Each cell was treated as a tank to characterize the
      conditions within the cell. In the model, when the reservoir boundaries coincide
      with the position of the siphons, the signal simulated is sensitive to input
      pulses of the recharge. This supports the hypothesis that the siphons are the
      controlling mechanism in the flow system of the aquifer. The good agreement
      between predicted and measured discharges demonstrates the ability of the model
      to simulate the flow in the Itxina Aquifer. These results demonstrated that the
      hydraulic conductivity increases downstream within the aquifer. The hydraulic
      conductivities obtained by calibration varied between 4.2 x 10(-3) m/s upstream
      of the aquifer, 6.0 x 10(-2) m/s in the central region, and 9.5 x 10(-1) m/s in
      the lower region of the aquifer. These values seem reasonable because the
      underground features in the principal caves show that the density of caves
      increases downstream in the Itxina Aquifer. The simple representation of the
      system produced results comparable to traditional ground water models with fewer
      data requirements and calibration parameters.

PMID- 11340999
TI  - In situ determination of subsurface microbial enzyme kinetics.
AB  - The single-well, push-pull test has been used in previous field studies to
      measure in situ zero- and first-order rates for aerobic and anaerobic microbial
      respiration in the saturated zone. In this paper we demonstrate that the test can
      also be used to obtain more generalized descriptions of the kinetics of
      microbially mediated enzymatic reactions. Laboratory and field tests were
      performed with the model enzyme substrate p-nitrophenyl-beta-D-glucopyranoside
      (PNG). During a push-pull test, injected PNG is hydrolyzed in situ to p
      nitrophenol (PNP); the rate of PNP production is taken as a measure of the beta
      glucosidase activity expressed by indigenous microorganisms. Laboratory tests
      were performed in physical aquifer models packed with natural aquifer sediment;
      field tests were performed in a shallow unconfined alluvial aquifer at a
      petroleum contaminated site. The laboratory and field tests demonstrate that it
      is possible to compute the in situ rate of PNP production as a function of PNG
      concentration using only data from a single push-pull test. These data can then
      be used to estimate the Michaelis-Menton kinetic parameters Vmax and Km for the
      hydrolysis reaction. This approach potentially extends the range of applicability
      of the push-pull test approach for use in determining kinetic parameters for a
      wide range of microbial processes in situ. These could include the broad class of
      substituted nitrophenyl substrates used to assay other enzyme systems, as well as
      microbially mediated redox reactions that occur during contaminant
      transformations.

PMID- 11341000
TI  - Coefficient of permeability determined by measurable parameters.
AB  - Selection of a coefficient of permeability or the hydraulic conductivity in
      practical situations has required a fair amount of judgment and the expectation
      of accuracy can range over an order of magnitude. A determination of the
      coefficient based on measurable characteristics would greatly reduce the judgment
      aspect. The coefficient of permeability of a porous media can be derived from the
      following measurable parameters: the density and viscosity of the permeating
      fluid, the porosity of the media, the average hydraulic radius of the pores, and
      the gravitation constant. The hydraulic radius is calculated from the grain size
      distribution analysis of the porous media assuming spherical particles and a
      factor to account for the shape of the particles. The shape factor ranges from
      1.0 to 1.4 in the extreme but, for common porous media, ranges only from 1.0 to
      about 1.1. All of the variables, except the shape factor, are measurable by
      standard test procedures. An important advantage of using this procedure for
      determining permeability is that the factors can be visualized as part of the
      physical flow process. The procedure assumes laminar flow and applies equally to
      liquid or gas fluids.

PMID- 11341001
TI  - A variable-volume, head-dependent mine water filling model.
AB  - Current simple mine water filling models suffer from two drawbacks: (1) they
      often do not account for variations in mine void volume with depth; and (2) they
      assume that recharge to the mine is approximately constant. The Mine Water
      Filling Model (MIFIM) presented here rectifies these drawbacks by presenting the
      concept of effective area (Ea) in a lookup table and assigning deep ground water
      inflows a conductance whereby inflow varies in inverse proportion to mine water
      head, once the mine water level exceeds the level of the water inflow. The MIFIM
      concept may be readily programmed in a computer spreadsheet environment, with
      simple graphical output. The approach is particularly suited to mines in low
      permeability rock, with a limited number of discrete inflow features.

PMID- 11341002
TI  - Analytical procedure for simultaneous use of seven fluorobenzoates in multitracer
      tests.
AB  - An analytical procedure allowing simultaneous use of seven fluorobenzoate (FBA)
      isomers was developed and examined through column and field tracer experiments.
      The analytical method, based on high performance liquid chromatography (HPLC),
      included a reverse-phase separation method. This method was found to be very
      efficient for the FBA analysis, allowing accurate determination of seven FBAs in
      a single HPLC run, while avoiding analytical interference of other natural water
      constituents or pollutants. Consequently, this separation method allows the
      simultaneous use of seven isomers in multitracer tests in highly saline or
      contaminated environments. The mobility properties of the FBAs were examined in
      percolation experiments through a column filled with a mixture of crushed chalk
      and common fracture filling and coating material. The FBAs behaved conservatively
      as compared to bromid. All seven FBA isomers were successfully used in a
      multitracer test in a field percolation experiment designed to identify flowpath
      along a fracture plane.

PMID- 11341003
TI  - Modeling preferential flow in reactive barriers: implications for performance and
      design.
AB  - Reactive barriers are passive and in situ ground water treatment systems.
      Heterogeneities in hydraulic conductivity (K) within the aquifer-reactive barrier
      system will result in higher flux rates, and reduced residence times, through
      portions of the barrier. These spatial variations in residence time will affect
      the treatment capacity of the barrier. A numerical flow model was used to
      evaluate the effects of spatial variations in K on preferential flow through
      barriers. The simulations indicate that the impact of heterogeneities in K will
      be a function of their location and distribution; the more localized the high K
      zone, the greater the preferential flow. The geometry of the reactive barrier
      will also strongly influence flow distribution. Aquifer heterogeneities will
      produce greater preferential flow in thinner barriers compared to thicker
      barriers. If the barrier K is heterogeneous, greater preferential flow will occur
      in thicker barriers. The K of the barrier will affect the flow distribution;
      decreasing the K of the barrier can result in more even distribution of flow.
      Results indicate that less variable flow will be attained utilizing thicker,
      homogeneous barriers. The addition of homogeneous zones to thinner barriers will
      be effective at redistributing flow only if installed immediately adjacent to
      both the up- and downgradient faces of the barrier.

PMID- 11341004
TI  - Use of NADP archive samples to determine the isotope composition of
      precipitation: characterizing the meteoric input function for use in ground water
      studies.
AB  - Stable oxygen and hydrogen isotopes have been used in ground water studies to
      investigate recharge, mixing, ground water/surface water interaction, advective
      diffusive transport, paleohydrogeologic interactions and to estimate ground water
      ages. Such studies require that the isotopic composition of precipitation be
      known, as precipitation is a major input to ground water and surface water
      systems. As oxygen-18 and deuterium data for precipitation are lacking across
      much of the United States, there is need to establish additional local meteoric
      water lines as isotope input functions across the region, as well as to develop
      better understanding of the isotopic climate linkages that control oxygen and
      hydrogen isotope ratios in precipitation. In the absence of long-term monitoring
      stations, one possible solution to this problem is to determine the delta 18O and
      delta 2H values of precipitation using archive samples collected at monitoring
      stations managed by the National Atmospheric Deposition Program (NADP). This
      study describes and interprets the seasonal delta 18O and delta 2H composition of
      archived precipitation samples collected in eastern Nebraska near the town of
      Mead during the years 1992-1994. Values for delta 18O range from -23.6 to 
      0.7@1000. Values for delta 2H range from -172 to 0@1000. Yearly arithmetic mean
      delta 18O and delta 2H values for the Mead station are -8.1@1000 and -53@1000,
      respectively. Weighted yearly means for delta 18O and delta 2H were -7.4@1000 and
      -48@1000, respectively. Mead values show a strong isotopic enrichment between
      winter and summer precipitation, and a strong delta 18O-T correlation (r2 = 0.91)
      for mean monthly values of about 0.5@1000 per degree Celsius. The local meteoric
      water line for the Mead site is delta 2H = 7.40 delta 18O + 7.32. Deuterium
      excess values suggest that most of the moisture across the region is derived
      primarily from a Gulf of Mexico source. The results of this study demonstrate
      that in the absence of long-term monitoring stations such as those operated
      globally by the International Atomic Energy Association, NADP archive samples can
      be used to determine the isotopic composition of precipitation, to characterize
      the local meteoric water line and establish the various climatic relationships,
      and define the meteoric input function for use in ground water studies.

PMID- 11341005
TI  - An assessment of a mesocosm approach to the study of microbial respiration in a
      sandy unsaturated zone.
AB  - Microbial respiration rates were determined through a 3.2 m thick, sandy
      unsaturated zone in a 2.4 m diameter x 4.6 m high mesocosm. The mesocosm was
      maintained under near constant temperature (18 degrees to 23 degrees C) and
      reached steady moisture content conditions after several hundred days. Soil-gas
      CO2 concentrations in the mesocosm ranged from 0.09% to 3.31% and increased with
      depth. Respiration rates within the mesocosm were quantified over a 342-day
      period using measured CO2 concentrations and a transient, one-dimensional finite
      element model. Microbial respiration rates were 2 x 10(-1) micrograms C.g-1.d-1
      throughout most of the system, but decreased to 10(-4) to 10(-3) micrograms C.g
      1.d-1 within the capillary fringe. Microbial respiration rates were also
      determined in minicosms (500 g sample mass) over a range in temperatures (4
      degrees to 30 degrees C) and volumetric moisture contents (0.044 to 0.37). The
      functional dependence of CO2 production on temperature and soil-moisture content
      was similar for the two scales of laboratory observation. Respiration rates in
      the minicosms, for temperatures and moisture contents in the mesocosm, were up to
      an order of magnitude greater than those determined for the mesocosm. The higher
      respiration rates in the minicosms, compared to the mesocosm, were attributed to
      greater disturbance of the samples and to shorter acclimation time in the
      minicosms. Extrapolating the laboratory respiration rates to field conditions
      yielded rates that were two to three orders of magnitude greater than rates
      previously determined in situ for C-horizon material. Results show that in situ
      microbial reaction rates determined using disturbed samples in minicosms and
      mesocosms yielded respiration rates that greatly exceeded field conditions.
      Mesocosms can, however, provide a useful environment for conducting process
      related research in unsaturated environments.

PMID- 11341006
TI  - Comparison of upscaling methods to estimate hydraulic conductivity.
AB  - A hydraulic field test program was performed at a hard rock laboratory (Aspo HRL)
      on the Swedish east coast to test upscaling theories. The test program
      investigated the rock volume around a borehole located at a depth of
      approximately 340 m below sea level. Hydraulic packer tests were performed at
      various scales, from 2 m to the entire borehole length of 296 m. From this set of
      data the predictive ability of different upscaling methods could be evaluated.
      The comparison of the evaluated "true" field scale hydraulic conductivity with
      the upscaled hydraulic conductivity yielded that the majority of the upscaling
      methods tested in this paper predict the large scale values with significant
      accuracy. However, the ability to predict rapidly decreases when the variance of
      the natural logarithm of hydraulic conductivity of the subsamples is larger than
      one. Such a variance is consistently found in the crystalline rocks at the tested
      site at the 2 m scale. However, at scales of 10 m and larger, a variance larger
      than one is uncommon. Therefore, it is concluded that there exists a smallest
      possible scale for use of hydraulic pumping test results for estimating the
      effective hydraulic conductivity at scales typical for regional flow.

PMID- 11341007
TI  - Delineating ground water recharge from leaking irrigation canals using water
      chemistry and isotopes.
AB  - Across the Great Plains irrigation canals are used to transport water to
      cropland. Many of these canals are unlined, and leakage from them has been the
      focus of an ongoing legal, economic, and philosophical debate as to whether this
      lost water should be considered waste or be viewed as a beneficial and reasonable
      use since it contributes to regional ground water recharge. While historically
      there has been much speculation about the impact of canal leakage on local ground
      water, actual data are scarce. This study was launched to investigate the impact
      of leakage from the Interstate Canal, in the western panhandle of Nebraska, on
      the hydrology and water quality of the local aquifer using water chemistry and
      environmental isotopes. Numerous monitoring wells were installed in and around a
      small wetland area adjacent to the canal, and ground water levels were monitored
      from June 1992 until January 1995. Using the water level data, the seepage loss
      from the canal was estimated. In addition, the canal, the monitoring wells, and
      several nearby stock and irrigation wells were sampled for inorganic and
      environmental isotope analysis to assess water quality changes, and to determine
      the extent of recharge resulting from canal leakage. The results of water level
      monitoring within study wells indicates a rise in local ground water levels
      occurs seasonally as a result of leakage during periods when the canal is filled.
      This rise redirects local ground water flow and provides water to nearby wetland
      ecosystems during the summer months. Chemical and isotopic results were used to
      delineate canal, surface, and ground water and indicate that leaking canal water
      recharges both the surface alluvial aquifer and upper portions of the underlying
      Brule Aquifer. The results of this study indicate that lining the Interstate
      Canal could lower ground water levels adjacent to the canal, and could adversely
      impact the local aquifer.

PMID- 11341008
TI  - Travel-time based model of bioremediation using circulation wells.
AB  - Vertical circulation wells can efficiently provide microorganisms with substrates
      needed for enhanced bioremediation. We present a travel-time based approach for
      modeling bioreactive transport in a flow field caused by a series of circulation
      wells. Mixing within the aquifer is due to the differences in sorption behavior
      of the reactants. Neglecting local dispersion, transport simplifies to a single
      one-dimensional problem with constant coefficients for each well. Recirculation
      is characterized by the discharge densities over travel time. We apply the model
      to the stimulation of cometabolic dechlorination of trichloroethene (TCE) by
      alternate injection of oxygen and toluene into the circulation wells. Mixing
      within the wells can be minimized by interposing sufficiently long breaks between
      the oxygen and toluene pulses. In our simulation, the proposed injection scheme
      stimulates biomass growth without risking biofouling of the aquifer.

PMID- 11341009
TI  - Arsenic in glacial drift aquifers and the implication for drinking water--lower
      Illinois River Basin.
AB  - The lower Illinois River Basin (LIRB) covers 47,000 km2 of central and western
      Illinois. In the LIRB, 90% of the ground water supplies are from the deep and
      shallow glacial drift aquifers. The deep glacial drift aquifer (DGDA) is below
      152 m altitude, a sand and gravel deposit that fills the Mahomet Buried Bedrock
      Valley, and overlain by more than 30.5 m of clayey till. The LIRB is part of the
      USGS National Water Quality Assessment program, which has an objective to
      describe the status and trends of surface and ground water quality. In the DGDA,
      55% of the wells used for public drinking-water supply and 43% of the wells used
      for domestic drinking water supply have arsenic concentrations above 10
      micrograms/L (a new U.S. EPA drinking water standard). Arsenic concentrations
      greater than 25 micrograms/L in ground water are mostly in the form of arsenite
      (AsIII). The proportion of arsenate (AsV) to arsenite does not change along the
      flowpath of the DGDA. Because of the limited number of arsenic species analyses,
      no clear relations between species and other trace elements, major ions, or
      physical parameters could be established. Arsenic and barium concentrations
      increase from east to west in the DGDA and are positively correlated. Chloride
      and arsenic are positively correlated and provide evidence that arsenic may be
      derived locally from underlying bedrock. Solid phase geochemical analysis of the
      till, sand and gravel, and bedrock show the highest presence of arsenic in the
      underlying organic-rich carbonate bedrock. The black shale or coal within the
      organic-rich carbonate bedrock is a potential source of arsenic. Most high
      arsenic concentrations found in the DGDA are west and downgradient of the bedrock
      structural features. Geologic structures in the bedrock are potential pathways
      for recharge to the DGDA from surrounding bedrock.

PMID- 11341010
TI  - Modeling of a deep-seated geothermal system near Tianjin, China.
AB  - A geothermal field is located in deep-seated basement aquifers in the
      northeastern part of the North China Plain near Tianjin, China. Carbonate rocks
      of Ordovician and Middle and Upper Proterozoic age on the Cangxian Uplift are
      capable of yielding 960 to 4200 m3/d of 57 degrees C to 96 degrees C water to
      wells from a depth of more than 1000 m. A three-dimensional nonisothermal
      numerical model was used to simulate and predict the spatial and temporal
      evolution of pressure and temperature in the geothermal system. The density of
      the geothermal water, which appears in the governing equations, can be expressed
      as a linear function of pressure, temperature, and total dissolved solids. A term
      describing the exchange of heat between water and rock is incorporated in the
      governing heat transport equation. Conductive heat flow from surrounding
      formations can be considered among the boundary conditions. Recent data of
      geothermal water production from the system were used for a first calibration of
      the numerical model. The calibrated model was used to predict the future changes
      in pressure and temperature of the geothermal water caused by two pumping
      schemes. The modeling results indicate that both pressure and temperature have a
      tendency to decrease with time and pumping. The current withdrawal rates and a
      pumping period of five months followed by a shut-off period of seven months are
      helpful in minimizing the degradation of the geothermal resource potential in the
      area.

PMID- 11341011
TI  - A first estimate of ground water ages for the deep aquifer of the Kathmandu
      Basin, Nepal, using the radioisotope chlorine-36.
AB  - The Kathmandu Basin in Nepal contains up to 550 m of Pliocene-Quaternary fluvio
      lacustrine sediments which have formed a dual aquifer system. The unconfined sand
      and gravel aquifer is separated by a clay aquitard, up to 200 m thick, from the
      deeper, confined aquifer, comprised of Pliocene sand and gravel beds,
      intercalated with clay, peat, and lignite. The confined aquifer currently
      provides an important water supply to the central urban area but there are
      increasing concerns about its sustainability due to overexploitation. A limited
      number of determinations of the radioisotope 36Cl have been made on bore waters
      in the basin, allowing us to postulate on the age of ground water in the deeper,
      confined aquifer. Ground water evolution scenarios based on radioisotope decay,
      gradual dissolution of formational salts as the ground waters move downgradient,
      and flow velocity estimations produce comparable ground water ages for the deep
      waters, ranging from 200,000 to 400,000 years. From these ages, we deduce a mean
      ground water flow velocity of only 45 mm/year from recharge in the northeast to
      the main extraction region 15 km to the southwest. We thus estimate current
      recharge at about 5 to 15 mm/year, contributing 40,000 to 1.2 million m3/year to
      the ground water system. Current ground water extraction is estimated to be 20
      times this amount. The low specific discharge confirms that the resource is being
      mined, and, based on current projections, reserves will be used up within 100
      years.

PMID- 11341012
TI  - Storage coefficient revisited: is purely vertical strain a good assumption?
AB  - The storage coefficient that is used ubiquitously today was first defined by the
      analytical work of Theis and Jacob over a half-century ago. Inherent within this
      definition is the restriction of purely vertical compression of the aquifer
      during a reduction in pressure. The assumption is revisited and quantitatively
      evaluated by comparing numerical results using both one- and three-dimensional
      strain models in the presence of three-dimensional flow. Results indicate that
      (1) calculated hydraulic head values are nearly identical for both models; (2)
      the release of water from storage in terms of volume strain is nearly identical
      for both models and that the location of maximum production moves outward from
      the well as a function of time; (3) the vertical strain components are markedly
      different with at least 50% of the total volume of water pumped originating from
      horizontal strain (and increasing to as much as 70%); and (4) for the one
      dimensional strain model to yield the necessary quantity of water to the pumped
      well, the resulting vertical compaction (land subsidence) is as much as four
      times greater and vertical strain is as much as 60% greater than the three
      dimensional strain model. Results indicate that small changes in porosity
      resulting from horizontal strain can yield extremely large quantities of water to
      the pumping well. This study suggests that the assumption of purely vertical
      strain used in the definition of the storage coefficient is not valid.

PMID- 11341013
TI  - Noninvasive determination of the location and distribution of DNAPL using
      advanced seismic reflection techniques.
AB  - Recent advances in seismic reflection amplitude analysis (e.g., amplitude versus
      offset-AVO, bright spot mapping) technology to directly detect the presence of
      subsurface DNAPL (e.g., CCl4) were applied to 216-Z-9 crib, 200 West Area, DOE
      Hanford Site, Washington. Modeling to determine what type of anomaly might be
      present was performed. Model results were incorporated in the interpretation of
      the seismic data to determine the location of any seismic amplitude anomalies
      associated with the presence of high concentrations of CCl4. Seismic reflection
      profiles were collected and analyzed for the presence of DNAPL. Structure contour
      maps of the contact between the Hanford fine unit and the Plio/Pleistocene unit
      and between the Plio/Pleistocene unit and the caliche layer were interpreted to
      determine potential DNAPL flow direction. Models indicate that the contact
      between the Plio/Pleistocene unit and the caliche should have a positive
      reflection coefficient. When high concentrations of CCl4 are present, the
      reflection coefficient of this interface displays a noticeable positive increase
      in the seismic amplitude (i.e., bright spot). Amplitude data contoured on the
      Plio/Pleistocene-caliche boundary display high values indicating the presence of
      DNAPL to the north and east of the crib area. The seismic data agree well with
      the well control in areas of high concentrations of CCl4.

PMID- 11341014
TI  - [MRI in the diagnosis of tumors of the shoulder girdle area].
AB  - The aim of the study was to estimate the value of MRI for evaluation tumors of
      the shoulder girdle. We diagnosed respectively 13 patients with lesions in the
      shoulder region. The imaging has been done with a "Magnetom SP 63" (Siemens,
      Erlangen, Germany). The protocol consisted of T1- and T2-based SE-sequences in
      axial slice orientation, T1-based imaging in coronary respectively in sagittal
      slice orientation as well as T1-based sequences after application of contrast
      medium. The evaluation of the tumor expansion within the soft tissue was
      possible. The exact diagnosis in some individual cases--neurinoma, cyst of the
      synovia--could be found by MRI. Estimation of the dignity in the case of
      infiltrative growth was possible in most cases. To assess the exact type of tumor
      was often difficult. Especially the dignity of the cartilaginous tumors could not
      be precisely described.

PMID- 11341015
TI  - [Digital mammography].

PMID- 11341016
TI  - [MRI of the intratemporal N. facialis].

PMID- 11341017
TI  - [Radiotherapy in vertebral hemangioma].
AB  - Vertebral hemangiomas are the most common benign spinal tumors with an incidence
      range of 10-12%. Approximately 1-2% of the cases develop clinically significant
      symptoms causing the necessity for treatment. Based on our own results and a
      review of the literature we discuss the role of radiotherapy in the management of
      symptomatic vertebral hemangiomas. A total dose of 30.0 Gy given in five weekly
      fractions of 2.0 Gy has been proven as effective for the primary treatment and
      postsurgical irradiation for the prevention of a recurrence. In the literature
      review the results are summarized of 59 reports in the period of 1929-2000 for a
      total of 327 cases. The analysis of 55 studies reporting results in 210 cases
      which underwent primary radiotherapy or combinations with other methods of
      treatment demonstrated that in 54% occurred a complete relief of symptoms (CR),
      in 32% a partial relief (PR), and 11% were non-responders (NR). The analysis of
      21 reports of 63 cases which were treated with radiotherapy as the sole measure
      of treatment demonstrated that 57% had a complete remission of symptoms (CR), 32%
      a partial remission (PR), and 11% did not respond to radiotherapy (NR). We
      conclude that radiation therapy is very effective in the management of
      symptomatic vertebral hemangiomas. With regard on the delayed effects of the
      irradiation, cases with an acute compression of the spinal cord should be treated
      primarily with a surgical procedure and a postsurgical irradiation is recommended
      to prevent a relapse of symptoms. In order to minimise acute or late toxicity and
      the risk of radiation-induced neoplasms the total dose should not exceed 30 Gy.

PMID- 11341019
TI  - [Pitfall: gastric atony vs. abscess of the bursa omentalis].

PMID- 11341018
TI  - [Treatment of rectal carcinoma].

PMID- 11341020
TI  - [Questions and countermeasure of plant protection in produce of Chinese medicinal
      materials].
AB  - Based on large inquest, the authors point out the questions of plant protection
      in produce of Chinese medicinal materials, meanwhile present the methods to solve
      them and list the research subjects which now must be down.

PMID- 11341021
TI  - [A resource investigation and commodity identification of Fructus Amomi].
AB  - Resource investigation and commodity identification were carried out for 28
      samples of Fructus Amomi collected from 7 provinces. The results showed that
      Fructus Amomi used currently were mainly from the dried ripe-fruit of Amomum
      villosum, A. villosum var. xanthioides or A. longiligulare. Fructus Amomi in
      market is nainly A. villosum which comes from Yunnan and Guangdong province.

PMID- 11341022
TI  - [A pharmacognostical study on Eomecon chionathe Hance].
AB  - The morphological and histological characters for the identification of Eomecon
      chionathe Hance was illustrated in this paper.

PMID- 11341023
TI  - [Pharmacognostical identification of Cistanche tubelosa a confused species of
      Cistanche deserticola].
AB  - Pharmacognostical studies on the descriptions, microscopic character, TLC and UV
      of Cistanche tubelosa a confused species of Cistanche deserticola were carried
      out and compared with that of Cistanche deserticola to provide a evidence for
      their identification.

PMID- 11341024
TI  - [Identification of traditional Chinese medicine Baizhi with near-infrared
      spectrum].
AB  - In this paper, 8 kinds of traditional Chinese medicines Baizhi were identified by
      near-infrared spectrum, coping with pattern recognition. The results showed that
      near-infrared spectrum method in identifying traditional Chinese medicines Baizhi
      was not only simple, rapid, but also using few examples, noninvasion. This method
      provided referential information for identifying these traditional Chinese
      medicines.

PMID- 11341025
TI  - [Identification of a confused species of Euphorbia hirta L. E. indica Lam].
AB  - The article reported the morphological and histological identification for
      Euporbia hirta L. and its confused species E. indica Lam.. It provided evidences
      for identifying Euphorbia hirta L..

PMID- 11341026
TI  - [Pharmacognostical studies on cortex Indigoferae Pseudotinctoriae].
AB  - This paper reported the studies on descriptions, microscopical characteristics of
      cross section and podwer, chemical examination and TLC of Cortex indigoferae
      pseudotinctoriae. These studies provided referential information for clinics,
      quality control, development and identification of this crude drug.

PMID- 11341027
TI  - [Isolation and identification of two steroids from Sinularia inexplicita].
AB  - Sinularia inexplicita collected from the South China Sea was studied with
      chromatography, two steroids were isolated. Based on the spectral data and
      elemental analysis, they were identified as 24-methylene-cholestane-3 beta,5
      alpha,6 beta,19-tetrol and grogosterol respectively.

PMID- 11341028
TI  - [Isolation, purification and determination of polysaccharides X-C-3-III and X-C-3
      IV from Angelica sinensis (Oliv) Diels].
AB  - Polysaccharides X-C-3-III and X-C-3-IV had been obtained from Angelica sinensis
      (Oliv) Diels. Their average MW were determined to be 85,000 and 65,765 by gel
      chromatography after the hydrolysates of X-C-3-III and X-C-3-IV, the compositions
      of them were identified by silanization method and capillary gas chromatography.
      X-C-3-III and X-C-3-IV are composed of galacose, arabinose, rhamnose, glucuronic
      acid and galacturonic acid. The molar ratio of those sugars were determined as
      24.3:15.8:4.2:3.1:52.6 and 12.6:10.7:7.2:8.3:61.2, respectively.

PMID- 11341029
TI  - [Antidepressant effect of water decoction of Rhizoma acori tatarinowii in the
      behavioural despair animal models of depression].
AB  - OBJECT: To assess the antidepressant effect of the water decoction of Rhizoma
      acori tatarinowii. METHODS: By using the rat forced swimming test and mouse tail
      suspension test models of depression, the antidepressant effect of Rhizoma acori
      tatarinowii was observed. RESULTS: The water decoction of Rhizoma acori
      tatarinowii and Fluoxetine significantly shortened motionless time of rat forced
      swimming and despair time of mouse tail suspension in the two behavioural despair
      animal models of depression. Antidepressant effect of water decoction of Rhizoma
      acori tatarinowii showed dose-dependence in the certain degree. The effect of
      water decoction of Rhizoma acori tatarinowii was weaker than that of Fluoxetine.
      There was a significant difference between every dose group of Rhizoma acori
      tatarinowii and saline control group. CONCLUSION: The water decoction of Rhizoma
      acori tatarinowii possessed obviously antidepressant effect in the behavioural
      despair animal models of depression.

PMID- 11341030
TI  - [Anti-inflammatory effect of saucernetilignan-8].
AB  - Saucernetilignan-8 (Sc-8), which was isolated from Saururus chinesis, has
      significant anti-inflammatory effect.

PMID- 11341031
TI  - [Studies on the supercritical-CO2 fluid extraction of complex prescription
      Danshen-Jiangxiang].
AB  - This paper first reported the supercritical-CO2 fluid extraction of complex
      prescription Danshen-Jiangxiang. With the active constituents and yield of
      extracts as index, the each other effect of each drug and effect on total complex
      prescription in extraction were studied. And the effects of pressure and
      temperature were also studied. The results showed the effects were different in
      complex prescription extraction and single prescription. Active constituents can
      be extracted, but a obvious effect exist each other and effects together the
      yield of extract, extraction rate and content of active constituents of complex
      prescription extraction, which are concerned in extraction conditions. These
      study results have important reference on the modernization of traditional
      Chinese medicines.

PMID- 11341032
TI  - [Extraction technology of Fructus Psoraleae with orthogonal test].
AB  - The extraction conditions of Fructus Psoraleae were studied with orthogonal test,
      taking the contents of psoralen and isopsoralen as indexes and smesh degree,
      alcohol concentration, alcohol volume, immersion time and immersion times as
      factors. The results showed the optimal extraction process is pulverizing the
      herbs into 20 meshes powder, 6 times volume of 55% alcohol immersed three times
      and two days every time.

PMID- 11341033
TI  - [Determination of protocatechualdehyde in yu xue bi granula].
AB  - The content of Protocatechualdehyde in YuXueBi granula was determined by HPLC.
      The chromatographic column was packed with ODS-2 (particle size 5 microns). The
      mobile phase was MeOH-H2O-H3PO4(17:83:0.003) adjusted to pH 3 with N(C2H5)3. The
      detection wavelength was 280 nm. The velocity of flow was 1.0 ml/min. The average
      recovery rate was 96.14%, RSD was 1.16%. The method was simple and stable.

PMID- 11341034
TI  - Nontoxic potentiation of cancer chemotherapy by dietary oligofructose or inulin.
AB  - Our previously published results indicated that dietary treatment with
      oligofructose or inulin inhibited malignant tumor growth in experimental animals.
      Thus it appeared to be interesting to investigate whether the same treatment
      could have a positive influence on tumor chemotherapy. The chemotherapy
      potentiating effect of 15% oligofructose or inulin incorporated into the basal
      diet for experimental animals was investigated on a transplantable mouse liver
      tumor. This dietary adjuvant therapy was started seven days before
      intraperitoneal transplantation of transplantable liver tumor and was continued
      until the end of experiments. A single, subtherapeutic dose of six different
      cytotoxic drugs commonly utilized in treatment of human cancer was
      intraperitoneally injected 48 hours after tumor transplantation. In all
      experiments, dietary oligofructose or inulin significantly potentiated the
      therapeutic effects of six different cytotoxic drugs. Such dietary treatment
      potentiating cancer chemotherapy could be introduced into classical protocols of
      human cancer treatment as a new, nontoxic, and easily applicable adjuvant cancer
      therapy without any supplementary risk for patients.

PMID- 11341035
TI  - Lack of effect of the flavonoids, myricetin, quercetin, and rutin, on repair of
      H2O2-induced DNA single-strand breaks in Caco-2, Hep G2, and V79 cells.
AB  - In the present study the effects of three flavonoids on the repair of H2O2
      induced DNA strand breaks were investigated in Caco-2, Hep G2, and V79 cells. At
      the concentrations used, myricetin, quercetin, rutin, and H2O2 did not
      significantly affect cell viability in all the cell lines. Catalase activity was
      measured in V79 cells and was found to be considerably lower than activities
      previously measured in Caco-2 and Hep G2 cells. Cells were exposed to 50 microM
      H2O2 for 0.5 hour at 37 degrees C. After treatment, DNA strand break repair in
      H2O2-treated cells was monitored at various time points over a 48-hour period
      using the alkaline single-cell gel electrophoresis assay. Caco-2 cells repaired
      faster than Hep G2 cells, which repaired considerably faster than V79 cells.
      Preincubation with 50 microM quercetin for 24 hours significantly decreased the
      extent of H2O2-induced DNA single-strand breaks throughout repair time points in
      Caco-2 cells (p < 0.05), but not in Hep G2 cells. Myricetin (50 microM) and rutin
      (50 microM) had no effect on repair in Caco-2 and Hep G2 cells. Preincubation for
      10 hours with quercetin and rutin, but not myricetin, significantly decreased the
      initial extent of DNA damage induced by H2O2 in V79 cells (p < 0.05). However,
      from the results of this study, none of the three flavonoids increased the rate
      of repair of strand breaks in any of the cell types.

PMID- 11341036
TI  - Flavonoids suppress androgen-independent human prostate tumor proliferation.
AB  - The present studies compared the effects of selected bioflavonoids on the
      proliferation of androgen-independent human prostatic tumor cells (PC-3).
      Complete growth retardation was observed in PC-3 cells treated with 100 microM
      quercetin, kaempferol, and luteolin, while isomolar genistein, apigenin, and
      myricetin suppressed PC-3 proliferation by 73%, 70%, and 59%, respectively (p <
      0.05). Naringenin and rutin were not as effective and inhibited growth by < 25%.
      Exposure to increasing concentrations of quercetin and kaempferol led to a dose
      dependent decrease in proliferation. Refeeding kaempferol-treated cells (50
      microM) complete medium without the flavonoid resulted in a return toward control
      growth rates. Similar growth recovery was not observed in quercetin-treated
      cells. The antiproliferative response of PC-3 cells to quercetin and kaempferol
      was additive when supplemented to the medium at 25 microM. A block in G2-to-M
      phase progression was observed after the addition of 25 microM kaempferol. When
      quercetin reached 100 microM, an increase in the proportion of cells in the S
      phase became apparent within 24 hours. Apoptosis was not evident, even when
      concentrations of quercetin or kaempferol were raised to 100 microM. The present
      studies suggest that alterations in cell cycle progression contribute
      significantly to the antiproliferative effects of quercetin and kaempferol in PC
      3 cells.

PMID- 11341037
TI  - Molecular mechanisms of cell cycle block by methionine restriction in human
      prostate cancer cells.
AB  - Previous studies have shown that dietary or pharmacological methionine
      restriction inhibits growth of human prostate cancer cells in vitro or as
      xenografts in mice. We undertook the present studies to clarify the molecular
      mechanisms by which methionine restriction inhibits prostate cancer cell growth.
      We found that PC-3 and DU 145 cells stopped proliferating within six days in
      growth medium containing homocysteine in place of methionine. In contrast,
      proliferation of LNCaP cells was only partially inhibited by the absence of
      methionine. Using flow cytometry, we found that methionine restriction caused PC
      3 cells to arrest in all phases of the cell cycle, but predominantly in the G2/M
      phase, whereas LNCaP cells accumulated exclusively in the G1 phase. Methionine
      restriction led to accumulation of the cyclin-dependent kinase inhibitors p21 and
      p27, as determined by Western blot analysis, and inhibited the enzymatic
      activities of the cyclin-dependent kinases CDK2 and cdc2, as determined by an in
      vitro kinase assay: However, methionine restriction had little or no effect on
      CDK2 or cdc2 protein levels. Methionine restriction also induced PC-3 cells to
      undergo apoptosis, as indicated by the appearance of a typical nucleosomal ladder
      on gel electrophoresis of genomic DNA. We conclude that methionine restriction
      has potential as a novel treatment strategy for prostate cancer.

PMID- 11341038
TI  - Foods and nutrients in relation to bladder cancer risk: a case-control study in
      Aichi Prefecture, Central Japan.
AB  - To elucidate the role of diet in the etiology of bladder cancer, we conducted a
      case-control study from 1996 to 1999 in Aichi Prefecture, Central Japan. Cases
      were patients newly diagnosed with bladder cancer, and one hospital control was
      selected for each case, matching gender, age, and hospital. A well-validated food
      frequency questionnaire was adopted to estimate intakes of nutrients and food
      groups. Odds ratios (ORs) adjusted for smoking and occupational history were
      computed using conditional logistic models. The analyses based on 297 cases and
      295 controls revealed the following. 1) The more the intake of milk and dairy
      products, the lower the OR; the ORs across quartiles in all subjects were 1.02,
      0.73, and 0.52. Fruit intake was negatively associated with the risk,
      particularly in men (ORs across quartiles = 0.76, 0.77, and 0.52). Green-yellow
      vegetables were associated with a decreased risk in the highest quartile of
      consumption in men (OR = 0.57). 2) Dietary intakes of retinol and saturated fatty
      acids were related to a reduced risk in all subjects (ORs across quartiles =
      0.75, 0.54, and 0.66 and 0.55, 0.54, and 0.60, respectively). Monounsaturated
      fatty acids had an inverse association with bladder cancer risk in men.

PMID- 11341039
TI  - Effect of curcumin on the apoptosis of rodent and human nonproliferating and
      proliferating lymphoid cells.
AB  - Curcumin, a major active component of turmeric, has been recognized as an
      anticarcinogenic agent because of its propensity to induce apoptosis in vivo and
      in vitro. Previously, we showed that curcumin protects cells against
      oligonucleosomal DNA fragmentation and induces a novel apoptosis-like pathway in
      Jurkat cells (Piwocka et al. Exp Cell Res 249, 299-307, 1999). Here, we have
      studied the ability of curcumin to induce cell death in other human and rodent
      transformed as well as normal cells. Normal cells were quiescent or stimulated to
      proliferate. We showed that 50 microM pigment is able to induce cell death in all
      studied cells, but cell death symptoms varied for different cells. All the cells
      died as assessed by the TdT-mediated UTP nick end labeling method or trypan blue
      exclusion test. No one type of cells showed oligonucleosomal DNA fragmentation
      (DNA "ladder") due to curcumin action, although in HL-60 cells, we were able to
      observe sub-G1 formation and caspase-3 activation. Together, these data showed
      that curcumin induces cell death in all tested cells that can be classified as
      apoptosis-like, and only in HL-60 cells can it be recognized as classical
      apoptosis.

PMID- 11341040
TI  - Vegetables, fruits, related dietary antioxidants, and risk of squamous cell
      carcinoma of the esophagus: a case-control study in Uruguay.
AB  - In 1998-1999, a case-control study on esophageal cancer was conducted in Uruguay.
      For this purpose, 111 cases with squamous cell carcinoma of the esophagus and 444
      controls with conditions unrelated to tobacco smoking, alcohol drinking, or
      recent changes in the diet were frequency matched on age, gender, residence, and
      urban/rural status. Vegetables and, more markedly, fruits were associated with
      strong reductions in risk. On the other hand, 12 of 15 dietary antioxidants
      displayed significant inverse associations with esophageal cancer risk. The
      strongest effect was observed for high intake of beta-cryptoxanthin (odds ratio =
      0.16, 95% confidence interval = 0.08-0.36). Also, alpha-carotene, lycopene, and
      beta-sitosterol were associated with significant reductions in risk. Most
      antioxidants lost their effect when they were further adjusted for a term for all
      vegetables and fruits. beta-Carotene showed an increased risk with high intakes.
      On the other hand, vegetables and fruits remained as significant variables after
      adjustment for each antioxidant, suggesting that other substances or other
      mechanisms could explain this effect.

PMID- 11341041
TI  - Effects of dietary, drinking, and smoking habits on the prognosis of gastric
      cancer.
AB  - Although it has been clarified that dietary, drinking, and smoking habits
      contribute to the onset of gastric cancer, little is known about their impact on
      prognosis of gastric cancer. To examine this question, a prognostic analysis was
      conducted using data from Aichi Cancer Center Research Institute and Hospital.
      From January 1988 to December 1994, information on 877 gastric cancer patients
      (578 men and 299 women) regarding habitual smoking and drinking, food
      consumption, histological grade, and clinical stage of tumor as well as follow-up
      results were collected. Survival status of all patients was followed up until
      December 1998, and the survival function was estimated by the Kaplan-Meier
      method. Proportional hazard analysis was used to test the effect of each
      lifestyle item on gastric cancer death. After controlling for age, gender,
      histological grade, and stage of disease, hazard ratios (HR) were calculated.
      Values for consumption of raw vegetables [HR = 0.74, 95% confidence interval (CI)
      = 0.56-0.98], tofu (HR = 0.65, 95% CI = 0.42-0.99), and chicken meat (HR = 0.61,
      95% CI = 0.39-0.95) more than three times per week demonstrated significantly
      decreased risk. However, the risk ratio was 2.53 (95% CI = 1.22-5.29) for
      habitual smokers, and an inverse dose-response relationship was also found
      between ever smoking and gastric cancer patient survival. Therefore, this study
      suggested that frequent intake of raw vegetables and tofu is favorable, whereas
      habitual smoking is an adverse prognostic factor for gastric cancer. Our study
      implies that an improvement of survival of Japanese gastric cancer might be
      achieved by lifestyle improvement.

PMID- 11341042
TI  - Total and monounsaturated fat intake and serum estrogen concentrations in
      premenopausal Japanese women.
AB  - The relationships between fat intake and serum estrone, estradiol, and sex
      hormone-binding globulin were examined cross-sectionally in 60 premenopausal
      Japanese women. Blood samples were collected on Day 11 of the menstrual cycle.
      Intake of fats, classified according to fat type, and other macro- and
      micronutrients was estimated on the basis of daily diet records from Day 2
      through Day 10 of the cycle. Total fat intake was significantly correlated with
      serum estrone concentration (Spearman r = 0.30, p = 0.02) and marginally
      significantly correlated with serum estradiol concentration (r = 0.26, p = 0.05)
      after controlling for age, total energy, and number of days before the next
      menses. Monounsaturated fat intake was significantly correlated with serum
      estrone (r = 0.32, p = 0.02) and serum estradiol (r = 0.27, p = 0.045). These
      data suggest an effect of dietary fat on serum estrogen concentrations.

PMID- 11341043
TI  - Oxidant stress and glioblastoma multiforme risk: serum antioxidants, gamma
      glutamyl transpeptidase, and ferritin.
AB  - Case-control studies of serum antioxidants are difficult to interpret, because
      antioxidants may be altered by the disease under study. However, because
      glioblastoma multiforme (GBM) is a relatively rare disease, a cohort study would
      require a large sample observed for many years. In the present case-control pilot
      study (34 cases and 35 controls), we evaluated the association between serum
      levels of ascorbic acid (AA) and alpha- and gamma-tocopherol (alpha-T and gamma
      T) measured before diagnostic surgery. To control for influence of GBM on serum
      AA, alpha-T, and gamma-T, we adjusted for oxidant stress indexes (gamma-glutamyl
      transpeptidase and uric acid) and an acute-phase response index (serum ferritin).
      When adjusted, AA is inversely related to GBM (p for trend = 0.007). In addition,
      AA interacts with alpha-T to further reduce GBM risk (test for interaction, p =
      0.04). gamma-T is not associated with GBM (p = 0.71). However, gamma-glutamyl
      transpeptidase (p = 0.004), coenzyme Q (p = 0.01), and ferritin (p = 0.009) are
      positively and uric acid (p = 0.000) is negatively related to GBM. We conclude
      that 1) AA and alpha-T are jointly related to GBM after adjustment for GBM
      produced oxidant stress and 2) there is a strong association between the presence
      of GBM and oxidant stress.

PMID- 11341044
TI  - Suppression of altered hepatic foci development by a high fish oil diet compared
      with a high corn oil diet in rats.
AB  - Effects of low corn oil, high corn oil, and high fish oil diets on altered
      hepatic foci development in female Sprague-Dawley rats were investigated. Rats
      assigned to Groups 1-4 were initiated with saline as the control and those
      assigned to Groups 5-7 were initiated with diethylnitrosamine (DEN 15 mg/kg) at
      24 hours of age. After weaning, all rats, except those in Group 1, received 500
      ppm phenobarbital (PB) in their diet as tumor promoter for three months. Altered
      hepatic foci development was significantly lower in DEN-initiated rats fed the
      high fish oil + PB diet than in DEN-initiated rats fed the high corn oil + PB
      diets. Liver weight and relative liver weight were significantly greater in rats
      fed the high fish oil + PB diet than in rats fed the other diets, and hepatic
      biotransformation/detoxification enzyme activities were greater in rats fed the
      fish oil + PB diets than in rats fed the other diets. These results suggest that
      the effect of a high fish oil diet on altered hepatic foci may occur through
      regulation of hepatic biotransformation/detoxification enzyme activities, leading
      to alteration in the tumor-promoting action of PB. Dietary lipid significantly
      affected the hepatic phospholipid fatty acid composition of rats. n-3
      polyunsaturated fatty acids were incorporated into membrane phospholipid at the
      expense of n-6 polyunsaturated fatty acids. A high fish oil diet caused greater
      oxidative stress in rats, as measured by plasma vitamin E level, red blood cell
      glutathione status, liver lipid peroxidation, and hepatic glutathione reductase
      activity. Pearson's correlation analysis indicated that the foci number was
      negatively correlated to the liver thiobarbituric acid-reactive substance and 7
      pentoxyresorufin O-dealkylase activity, and the foci area was negatively
      correlated to the liver thiobarbituric acid-reactive substance activity (p <
      0.05) in rats of groups that developed foci. These results suggest that the type
      of dietary lipid is the more important determinant for gamma-glutamyl
      transpeptidase-positive foci development than the amount of dietary lipid when
      rats consumed approximately the same amount of calories in all the dietary
      groups, and the underlying mechanisms may be partially ascribed to the
      antioxidant/oxidation status and biotransformation/detoxification system of rats.

PMID- 11341045
TI  - Diet and hepatocellular carcinoma: a case-control study in Greece.
AB  - We conducted a case-control study in Athens, Greece, to investigate the role of
      diet in the etiology of hepatocellular carcinoma (HCC). Subjects were 97 incident
      cases of HCC and 128 controls with no history of cancer admitted for minor
      ailments in three major hospitals. Information on diet was collected using a
      validated food frequency questionnaire, and infection with hepatitis virus B
      (HBV) or C (HCV) was assessed using third-generation assays. Data were modeled
      through multiple logistic regression. We found no evidence that vegetable intake
      may reduce the risk of HCC, as reported in earlier investigations. In a
      multivariate model, only consumption of milk and dairy products appeared to be
      inversely related to HCC risk (odds ratio = 0.70, 95% confidence interval = 0.49
      1.01), but the association was not statistically significant and is likely to
      have been generated by the multiple comparisons undertaken overall. Our data do
      not support an association of specific food groups or particular nutrients with
      the risk of HCC, whether positive or negative for HBV and/or HCV.

PMID- 11341046
TI  - Suppression of azoxymethane-induced preneoplastic lesions and inhibition of
      cyclooxygenase-2 activity in the colonic mucosa of rats drinking a crude green
      tea extract.
AB  - We determined the effects of a crude green tea extract given as drinking fluid on
      the promotion/progression phase of colon carcinogenesis in rats after induction
      of the neoplastic process by azoxymethane. Adult Wistar rats were given
      azoxymethane (15 mg/kg i.p.) once a week for two weeks. One week after the second
      injection, the rats were randomly divided into two groups. One group (n = 8)
      received daily prepared aqueous solutions of green tea extracts (GTE; 0.02%,
      wt/vol); the control group (n = 8) received tap water. After six weeks, rats
      receiving GTE showed a 60% reduction in the number of colonic preneoplastic
      lesions (aberrant crypts). The number of individual crypts per aberrant crypt
      focus (crypt multiplicity) was significantly reduced in the GTE group; the
      majority (80%) of the remaining aberrant foci contained only one or two
      preneoplastic crypts. A significant and selective decrease of cyclooxygenase
      (COX)-2 activity was observed in the colon of rats receiving GTE (23 +/- 3 vs.
      117 +/- 30 mU/mg protein in controls), whereas COX-1 showed no alterations. Our
      data demonstrate that GTE reduces COX-2 and suppresses the formation of colonic
      preneoplastic lesions. They provide new insights into the mechanism of
      chemopreventive and anti-inflammatory properties of green tea.

PMID- 11341047
TI  - A protective role of dietary vitamin D3 in rat colon carcinogenesis.
AB  - The aim of the present work was to gain insight into a putative anticancer effect
      of dietary vitamin D3 (cholecalciferol) in a rat model of colon carcinogenesis.
      Male rats were assigned to three different dietary groups. The dietary regimens
      were based on a standard murine-defined diet (AIN-76A) or a stress diet
      containing 20% fat, reduced Ca2+ concentration, a high phosphorus-to-Ca2+ ratio,
      and either low or high vitamin D3 content. Colorectal cancer was induced by
      administration of the procarcinogen 1,2-dimethylhydrazine (DMH). Blood Ca2+, 1,25
      dihydroxyvitamin D3 [1,25(OH)2D3], and 25-hydroxyvitamin D3 [25(OH)D3] levels
      were measured in DMH-treated rats and in respective weight- and age-matched
      dietary control groups. Colonic epithelial proliferation was assessed by
      determining thymidine kinase (TK) activity, bromodeoxyuridine (BrdUrd)
      incorporation into crypt cell DNA, and the mean labeling index along the colonic
      crypt continuum. Maintenance of rats on the stress diet either unmodified or
      supplemented with vitamin D3 in the absence of carcinogen treatment provoked a
      time-dependent rise in colonic TK activity and hyperproliferation of colonic
      epithelium. DMH treatment of rats maintained on the standard diet caused a marked
      increase in the proliferative indexes of colonic epithelium and in expansion of
      the crypt proliferative compartment. TK activity and the crypt mitotic zone were
      significantly augmented in the animal group fed the stress diet. Supplementary
      vitamin D3 abrogated the stress diet-enhanced colonic responses to the
      carcinogenic insult. Colon tumor multiplicity was fourfold higher in animals fed
      the stress diet than in animals maintained on a standard diet. The marked rise in
      colonic tumor multiplicity and adenocarcinoma incidence in rats fed the stress
      diet was obliterated by supplemental dietary vitamin D3. Cumulatively, the
      present results indicate that dietary vitamin D3 impedes the neoplastic process
      in murine large intestine and strengthen the view that inappropriate changes in
      dietary components and micronutrients are contributory determinants of colorectal
      cancer.

PMID- 11341048
TI  - Endogenous N-nitroso compounds, and their precursors, present in bacon, do not
      initiate or promote aberrant crypt foci in the colon of rats.
AB  - Processed meat intake is associated with increased risk of colorectal cancer.
      This association may be explained by the endogenous formation of N-nitroso
      compounds (NOC). The hypothesis that meat intake can increase fecal NOC levels
      and colon carcinogenesis was tested in 175 Fischer 344 rats. Initiation was
      assessed by the number of aberrant crypt foci (ACF) in the colon of rats 45 days
      after the start of a high-fat bacon-based diet. Promotion was assessed by the
      multiplicity of ACF (crypts per ACF) in rats given experimental diets for 100
      days starting 7 days after an azoxymethane injection. Three promotion studies
      were done, each in 5 groups of 10 rats, whose diets contained 7%, 14%, or 28%
      fat. Tested meats were bacon, pork, chicken, and beef. Fecal and dietary NOC were
      assayed by thermal energy analysis. Results show that feces from rats fed bacon
      based diets contained 10-20 times more NOC than feces from control rats fed a
      casein-based diet (all p < 0.0001 in 4 studies). In bacon-fed rats, the amount of
      NOC input (diet) and output (feces) was similar. Rats fed a diet based on beef,
      pork, or chicken meat had less fecal NOC than controls (most p < 0.01). No ACF
      were detected in the colon of bacon-fed uninitiated rats. After azoxymethane
      injection, unprocessed but cooked meat-based diets did not change the number of
      ACF or the ACF multiplicity compared with control rats. In contrast, the bacon
      based diet consistently reduced the number of large ACF per rat and the ACF
      multiplicity in the three promotion studies by 12%, 17%, and 20% (all p < 0.01).
      Results suggest that NOC from dietary bacon would not enhance colon
      carcinogenesis in rats.

PMID- 11341049
TI  - Effect of tea polyphenols and tea pigments on the inhibition of precancerous
      liver lesions in rats.
AB  - The objective of this study was to investigate the inhibitory effect of tea
      components, tea polyphenols and tea pigments, on precancerous liver lesions in
      rats. A rat liver precancerous lesion model was established by multiple low
      dosage N-nitrosodiethylamine (NDEA) injections, followed by intraperitoneal CCl4
      injection and partial hepatectomy (PH). Tea pigments (0.1%) or tea polyphenols
      (0.1%) were given to Wistar rats in drinking water during the eight weeks of the
      experiment. The number and area of glutathione S-transferase Pi-positive foci in
      the rat liver were used as biomarkers of precancerous liver lesions. Western and
      Northern blot techniques were used to detect rat liver GST-Pi expression at the
      protein and mRNA levels. At the end of the experiment, tea polyphenols and tea
      pigments significantly decreased the number and area of GST-Pi-positive foci that
      were overexpressed in the NDEA-CCl4-PH-treated rats compared with the positive
      control group. The results also showed that GST-Pi mRNA and protein expression
      increased significantly in the NDEA-CCl4-PH-treated group, which is consistent
      with the changing of GST-Pi-positive foci. Tea pigments and tea polyphenols had
      an inhibitory effect on the overexpression of GST-Pi mRNA and protein in NDEA
      CCl4-PH-treated rats. These results suggest that tea pigments and tea polyphenols
      are effective in preventing the occurrence and progression of precancerous liver
      lesions in rats.

PMID- 11341050
TI  - Effects of topical and oral vitamin E on pigmentation and skin cancer induced by
      ultraviolet irradiation in Skh:2 hairless mice.
AB  - This study investigates whether supplementation with topical RRR-alpha-tocopherol
      (Eol), topical RRR-alpha-tocopheryl succinate, and oral RRR-alpha-tocopheryl
      acetate can reduce the incidence of acute and chronic damage to the skin (i.e.,
      sunburn and pigmentation and skin cancer, respectively) induced by ultraviolet
      (UV) irradiation to mice. Groups of twenty Skh:2 female hairless pigmented mice
      were treated with 1) lotion vehicle, 2) 5% Eol lotion, 3) 5% topical RRR-alpha
      tocopheryl succinate lotion, or 4) lotion vehicle and oral RRR-alpha-tocopheryl
      acetate. Within each group, 15 mice were exposed to 0.24 J/cm2 of UV-B radiation
      three times per week. The animals' weights and food intakes were monitored, and
      the vitamin E concentrations of skin, liver, and adipose tissue were measured to
      determine whether the topical Eol resulted in significant tissue levels. Skin
      pigmentation was scored, and the total number of clinically detectable skin
      tumors per animal was counted weekly. Results showed that the skin concentrations
      of Eol, as well as levels in the adipose tissue, were increased after topical
      application. Mice treated with each form of vitamin E showed no signs of toxicity
      and had significantly less acute and chronic skin damage induced by UV
      irradiation, as indicated by reduced inflammation and pigmentation and by later
      onset and lesser incidence of skin cancer.

PMID- 11341051
TI  - Allium sativum potentiates suicide gene therapy for murine transitional cell
      carcinoma.
AB  - This study evaluated the synergistic effect of Allium sativum (AS) with suicide
      gene therapy for transitional cell carcinoma (TCC) of the bladder. Subcutaneous
      TCCs were established in syngeneic C3H/He mice with 1 x 10(5) MBT-2 cells. AS
      liquid extract was injected at the site of tumor transplantation on Day 1 for
      three weeks (Experiment I) and into the established tumors weekly for five weeks
      (Experiment II) in combination with or without gene therapy using a replication
      defective adenoviral vector containing a herpes simplex virus thymidine kinase
      (HSV-TK) gene under the transcriptional control of Rous sarcoma virus (RSV)
      promoter (Ad-RSV-TK, 5 x 10(8) plaque-forming units) plus ganciclovir (20
      mg/kg/day i.p.). AS demonstrated a statistically significant reduction in
      incidence of TCC (cumulative dose 25 mg of AS). Combination AS-suicide gene
      therapy significantly inhibited the tumor growth compared with the controls,
      which was evidenced by apoptosis on histomorphological and immunohistochemical
      studies. These results suggest that AS had a definite antitumor effect in
      inhibiting tumorigenesis and growth of TCC in a murine model. AS treatment
      combined with suicide gene therapy had significant additive antitumor effects on
      TCC and may provide a novel and effective treatment modality for TCC of the
      bladder.

PMID- 11341052
TI  - [General intubation anesthesia in primates for experimental otoneurologic
      surgery].
AB  - INTRODUCTION: We report our experience in anaesthetic and surgical management of
      primates (M. fascicularis) in an experimental otoneurosurgical procedure.
      MATERIAL & METHODS: The VIII cranial nerve was bilaterally sectioned in a
      translabyrinthine approach in 21 adult primates. In 14 animals subsequently, a
      prototype of auditory brainstem implant was placed unilateraly within the brain
      stem for surface stimulation of cochlear nuclei. Premedication consisted in an
      intramuscular mixture of ketamine, midazolam and atropine. Surgical procedure was
      performed under intubated general anaesthesia, after propofol (1.5 mg/kg)
      administration and maintained with nitrous oxide and halotane. RESULTS: The
      mixture of ketamine, midazolam and atropine produced a deep anaesthesia in 4 +/-
      1.7 minutes, permitting safe animal handling. Atraumatic nasotracheal intubation
      without muscle relaxing agents was easily achieved in all animals. Anaesthesia
      was adequately maintained with nitrous oxide and halotane. Animals did not
      present any relevant incidents during surgery, and were extubated 10 +/- 2.5
      minutes after cessation of gas administration. Post-operatively, no relevant
      surgical complications occurred. CONCLUSIONS: We report an anaesthetic technique
      that provides an optimal restrain and anaesthesia for experimental
      otoneurosurgical procedures with primates. This technique offers a quick recovery
      and avoids the use of muscular relaxing agents for intubation, and thus could be
      safely used in other kind of surgical procedures.

PMID- 11341053
TI  - [Role of surgery in the treatment of primary gastric lymphoma].
AB  - Primary gastric lymphoma's optimum management remains controversial. We reviewed
      our series of 23 patients with primary gastric lymphoma treated in our hospital
      between 1976 and 1998 with surgery as main therapy. Ten patients underwent
      surgical resection alone, whereas 13 also received postoperative adjuvant
      therapy, depending on the oncologist-haematologist's recommendations. No
      differences were found between treatments regarding mortality and morbidity.
      Clinical-histological features and patients, follow-up are analyzed. No patient
      died because of lymphoma and there wasn't either local or distant recurrence. We
      consider that surgery remains a valid option for the primary gastric lymphoma
      treatment. The introduction of combined modalities of radiation therapy and
      chemotherapy will depend on the final stage, the tumor histological features, and
      the feasibility of getting a radical resection.

PMID- 11341054
TI  - [Obesity in children].
AB  - Obesity during childhood and adolescence is an increasingly common complaint in
      our daily clinical practice. The increase in its prevalence makes paediatrician
      worry about this disease, which is now considered an epidemic by the World Health
      Organisation. Obesity is a complex disease. Its aetiology is not yet clear, due
      to the multiple factors involved: environment, genetics, behaviour, life style,
      neuroendocrinology and metabolism. Persistent obesity increases the risk of
      suffering from diabetes, cardiovascular disease, hypertension, and gallbladder
      disease. The treatment of obesity is problematic and there are few patients who
      persist on a long term weight reduction programme. A multidisciplinary approach
      is therefore required. Paediatricians, dieticians, nurses, psychologists and
      psychiatrist should intervene in the treatment programme. Dietary changes must
      combine a decrease in energy intake and an increase in energy expenditure,
      inculcating both healthy eating habits and lifestyle without interfering in the
      child's growth and development.

PMID- 11341056
TI  - [Aggressiveness: instinct or learned behavior].

PMID- 11341055
TI  - [Imaging problem case. Antral or prepyloric mucosal diaphragm].

PMID- 11341057
TI  - [Moxifloxacin].

PMID- 11341058
TI  - [Medical continuing education at the University of Navarra].

PMID- 11341059
TI  - The rebirth of the idols. The Freudian unconscious and the Nietzschean
      unconscious.
AB  - The author explores how psychoanalysis mutates in its passing from the privacies
      of the session to the public spaces of academia, shifting away from enquiry into
      unfolding unconscious psychic processes guided by its method, and from the
      clinically based notions Freud and his diverse followers constructed, here called
      the 'Freudian unconscious'. In postmodern intellectual contexts Freud's work
      fuels a 'Nietzschean unconscious', issuing from public lecterns in the
      protagonistic, self-creating feats of a 'psychoanalytic discourse'. The ideology
      of such mutation is here traced from Nietzsche on to Heidegger and Kojeve, and
      then to Lacan and Laplanche. It reflects the might of the 'death of evidences'
      and the Romantic penchant for the limit-experience and the primacy accorded to
      the creative imagination. Discourse as revelation rests on a 'paradox of the
      enunciation' whereby the subject (author) of the statement is taken to be
      identical to the subject (matter) of the statement. Banishing the boundaries of
      illusion and evidence, and of self-overcoming and insight, academic
      'psychoanalytic discourse' creates a 'return of the idols' in 'theoretical'
      narcissistic identification.

PMID- 11341060
TI  - The psychoanalyst of the future: wise enough to dare to be mad at times.
AB  - What sort of patients do we have in psychoanalysis now, at the beginning of the
      third millennium, and what sort will we have in the future? In the author's
      clinical experience, the patients who are currently seeking help from the
      psychoanalyst use primitive defence mechanisms alongside neurotic ones. Most of
      them do not explicitly request psychoanalytic treatment, but this does not mean
      that they would not want it if they knew what it was. She argues that is the
      psychoanalyst's task to identify the latent request behind the 'non-request'. To
      conduct a psychoanalysis with such patients, the psychoanalyst has to identify
      and interpret both primitive and neurotic psychic mechanisms; moreover, he has to
      use not only language that speaks to patients but also language that 'touches'
      them, because these patients are difficult to reach through verbal symbolism.
      This implies that the psychoanalyst must be attentive to the bodily
      manifestations and bodily phantasies accompanying his countertransference
      feelings. The author shows through clinical examples what she means by 'language
      that can touch patients'. The psychoanalyst gradually builds up this language
      while, at the same time, daring to discover in himself his own mad aspects and
      giving himself enough psychical freedom to accept them.

PMID- 11341061
TI  - The countertransference: erotic, erotised and perverse.
AB  - The author begins by drawing attention to the dearth of psychoanalytic theory on
      the sexual countertransference, which he attributes largely to embarrassment
      associated with the personal superego and to fear of censure by the
      psychoanalytic community. After a review of the relevant literature, he points
      out that the term 'countertransference' arose in the context of misbehaviour by
      the early analysts and that the countertransference was originally seen as
      something to be controlled and suppressed, partly for the sake of the reputation
      of psychoanalysis. Theoretical and normative reasons are adduced for the
      disappearance of sexuality from psychoanalytic scenarios, and the wish for sexual
      contact with patients is discussed. While it may be deemed perfectly normal for
      an analyst to have erotic feelings towards patients of either sex,
      psychopathology is, in the author's view, involved only if he acts out. Clinical
      illustrations are given of manifestations of the sexual countertransference in
      its erotic, erotised and perverse forms, which the author considers it important
      to distinguish. He concludes that the relative absence of theory on the subject
      means that not enough clinical use is made of the sexual countertransference,
      which he sees as of great potential value to therapist and patient alike.

PMID- 11341062
TI  - The dream's navel between chaos and thought.
AB  - The authors begin by drawing attention to the problem of the transition from the
      biological to the psychic, noting that Freud himself, with his background in the
      neurosciences, grappled with it throughout his career. Certain recent paradigms
      more commonly applied to the natural sciences, such as in particular chaos and
      complexity theory, can in their view prove fruitful in psychoanalysis too, and it
      is shown how these notions are inherent in some of Freud's conceptions. The
      unconscious is stated to operate like a neural network, performing the kind of
      parallel processing used in the computing of highly complex situations, whereas
      the conscious mind is sequential. Dreams, in the authors' opinion, are organisers
      of the mind, imparting order to the turbulence of the underlying wishes and
      unconscious fantasies and structuring them through the dream work. Through
      dreams, the structured linearity of conscious thought can emerge out of the non
      linear chaos of the drives. The dream's navel can be seen as the chaotic link, or
      interface, between the unconscious wish, which constitutes an attractor, and the
      conscious thought. The attractor may be visualised as having an hourglass or
      clepsydra shape, the narrow section being the dream's navel, and, being the same
      at any scale of observation, has the property of fractality.

PMID- 11341063
TI  - Abraham's discovery of the 'bad mother'. A contribution to the history of the
      theory of depression.
AB  - The author shows how, after Freud struggled in vain from the 1890s to develop a
      theory of depression, Abraham succeeded for the first time in finding an approach
      to the understanding of depression a few years before the publication of Freud's
      'Mourning and melancholia'. It is contained in his study of the painter Giovanni
      Segantini (1911), which also includes a description, imbued with a new
      atmospheric quality, of the mother-son relationship that centres on the concept
      of the 'bad mother'. The author points out that Abraham's 'good/bad' dimension is
      effectively absent from Freud's published work up to 1911 and is also at variance
      with his view of the relationship between son and mother. In later contributions,
      too, Abraham maintained that unconscious hate directed at the mother, who is
      experienced as 'bad' but longed for as 'good', was a central factor in the
      aetiology of depression, a view he had to defend vis-a-vis Freud. The author
      contends that in the Segantini paper Abraham was describing an inner world
      similar to that evinced by the work of Melanie Klein and significantly different
      from Freud's. It is characterised by hate, revenge, death wishes and guilt
      feelings on the one hand and tranquillity and inner peace on the other.

PMID- 11341064
TI  - Distinguishing the drama from the histrionics in a case of hysteria with multiple
      tics.
AB  - The author describes a clinical experience with a hysterical patient with
      multiple tics, an upper-middle class, married woman, who when she started
      analysis at the age of 30 was in a state of profound tension and anxiety. The
      first eight years of this analysis are presented in order to describe how the
      analyst came to identify the dynamics of unconscious phantasies in a situation
      where analyst and patient found themselves involved in several roles of a drama
      dominated by theatrics. The insights and therapeutic benefits suggested that this
      patient unconsciously experienced her oral needs as intensely destructive and
      cruel, an experience she felt to have been exacerbated by her mother's lack of
      response to her emotional needs. This primitive cruel orality was accompanied by
      a split-off experience of a secret, mystical union with the primitive idealised
      mother. The author considers that this split experience of cruel and idealised
      orality suffused the patient's genital sexuality, hindering the evolution and
      realisation of her adult sexuality, giving her a distorted view of the primal
      scene as an impenetrable fused amalgam acting as an omnipotent, self-sufficient,
      excluding phallus. Gradually analysis enabled the patient to transform her bodily
      theatrics into thoughts and to broach the difficult task of relating to others
      instead of being either fused with them or totally excluded by them.

PMID- 11341065
TI  - The 'Medea fantasy'. An unconscious determinant of psychogenic sterility.
AB  - The author begins by pointing out that myths have always been powerful vehicles
      for the projection of ubiquitous unconscious fantasies. Having noted the
      importance of certain male protagonists of the Greek myths in Freud's theories,
      she observes that their female counterparts exert an equal fascination and
      suggests that the Medea myth as recounted by Euripides can be invoked to
      elucidate a central unconscious fantasy found to underlie the psychogenic
      frigidity and sterility of several of her female patients. The manifestation of
      this 'Medea fantasy' is illustrated by a clinical account in which a dream is
      analysed. The author next summarises the Medea story as told by Euripides and
      attempts a psychoanalytic interpretation of it. She draws attention to features
      of the 'unconscious truth' inherent in the myth that were shared by all the
      members of her group of patients. A case history then shows how the progressive
      understanding and working through of the Medea fantasy led to a change in the
      analysand's experience of femininity and enabled her to have children. It is
      postulated that both early infantile sexual fantasies and repressed memories of
      early object-relations traumas such as maternal depression combine with
      ubiquitous bodily fantasies to produce the unconscious Medea fantasy.

PMID- 11341066
TI  - Cocaine addicts and their families. An empirical study of the processes of
      identification.
AB  - The processes of identification between adolescent cocaine addicts and their
      parents were studied in 402 subjects, in total 134 familial triads (father-mother
      son), subdivided into two groups of 67 triads, one of these groups having as the
      child an adolescent of masculine sex dependent on cocaine and the other, equal in
      number, being a control group, duly matched for age and socio-economic status.
      The instrument employed was the Rorschach test (1922), limited to the application
      of the Lerner Defense Scale (LDS; Lerner & Lerner, 1980). The findings in the
      affected triads showed up as consistent statistically for the presence of intense
      processes of pathological identification, especially between father and son, a
      sign of the importance of the presence of disturbances of paternal function in
      the development of this addiction. The utilisation of very regressive defence
      mechanisms, above all of projective identification, was the predominant mode of
      procedure in triads with a dependent child. In comparisons between the fathers
      the odds ratio (OR) for projective identification was 8.66 to 1, which points to
      the association between cocaine addiction and the primitive mental functioning of
      the fathers. With empirical methodology these findings serve to corroborate the
      psychoanalytical conclusions based on studies of single case studies, testifying
      that the dysfunctions of identificatory phenomena in familial functioning are
      predominant in the mental organisation of cocaine addicts.

PMID- 11341067
TI  - Freud and Klein on the concept of phantasy.
AB  - In summary, I think Freud's idea is that the prime mover of psychic life is the
      unconscious wish, not phantasy. The 'work' of making phantasies and the 'work' of
      making dreams are parallel processes in which forbidden unconscious wishes
      achieve disguised expression and partial fulfilment. For Freud himself,
      especially in his central usage, and even more for his immediate followers,
      phantasies are conceived as imagined fulfilments of frustrated wishes. Whether
      they originate in the system conscious or the system preconscious, they are an
      activity of the ego and are formed according to the principles of the secondary
      process. That is not the whole story, however, because phantasies may get
      repressed into the system unconscious, where they become associated with the
      instinctual wishes, become subject to the laws of the primary process, and may
      find their way into dreams and many other derivatives. For Freud and for French
      psychoanalysts particularly, there are the primal phantasies, 'unconscious all
      along', of the primal scene, castration and seduction, also capable of being
      directly incorporated into dreams and expressed through other derivatives. For
      Klein phantasy is an even more central concept than for Freud and it has
      continued to be used by her successors with only minor changes. In Klein's
      thinking unconscious phantasies play the part that Freud assigned to the
      unconscious wish. They underlie dreams rather than being parallel to them--a much
      more inclusive definition of phantasy than Freud's. The earliest and most deeply
      unconscious phantasies are bodily, and only gradually, with maturation and
      developing experience through introjection and projection do some of them come to
      take a verbal form. Freud's central usage, the wish-fulfilling definition of
      phantasy, is a particular type of phantasy within Klein's more inclusive
      definition. And, as in Freud's formulation, conscious phantasies may be
      repressed, but in Klein's formulation this is not the only or even the main
      source of unconscious phantasies. In Klein's usage, unconscious phantasies
      underlie not only dreams but all thought and activity, both creative and
      destructive, including the expression of internal object relations in the
      analytic situation. Finally, it is my tentative suggestion that conceptual and
      clinical focus on the concept of phantasy, especially unconscious phantasy, as in
      Britain and France, tends to involve a heightened awareness of the unconscious-
      hardly surprising, since unconscious phantasy is such a fundamental aspect of the
      unconscious. I have suggested that, although there are many individual
      variations, the structural model and the self-psychology, relational and
      intersubjectivist models tend to discourage focus on the dynamic unconscious.

PMID- 11341068
TI  - Hermeneutics.

PMID- 11341069
TI  - Envy, jealousy and shame.

PMID- 11341070
TI  - IPA overview panel.

PMID- 11341071
TI  - Responses to Colette Chiland's 'the psychoanalyst and the transsexual patient'.

PMID- 11341072
TI  - Responses to Collette Chiland's 'the psychoanalyst and the transsexual patient'.

PMID- 11341073
TI  - Toxicology and immunotoxicology of mercury: a comparative review in fish and
      humans.
AB  - This review addresses an important area of environmental and mammalian toxicology
      by evaluating and comparing mercury-induced effects upon the immune responses of
      two evolutionarily divergent yet immunologically-related species. The mechanisms
      of mercury toxicology and immunotoxicology are described herein, including
      supporting data from the following: sources of exposure; bioavailability and
      biodistribution; metabolism; and laboratory and field investigations. Based upon
      the studies presented, the relative sensitivities of fish and human immune cells
      to mercury exposure are compared and contrasted with regard to mercury's ability
      to stimulate and/or suppress host immunocompetence. In addition, results from
      immune assays are compared to mercury tissue burdens, as well as to toxicological
      threshold level estimates. Such comparisons may help to resolve gaps in our
      knowledge regarding sensitivity of immunological assays, standardization of
      immunotoxicological techniques between species, and the extent to which the
      vertebrate immune system possesses functional reserve and redundancy in response
      to xenobiotics. A review of this type begins to provide support for the potential
      usefulness of fish immune cells to serve as indicators for human immunotoxicology
      risk assessment. Analysis of the reviewed studies supports the following
      conclusions in both lower and higher vertebrates: a threshold for mercury-induced
      immunotoxicological effects is likely; multiple exposure scenarios involving high
      and/or chronic exposures leading to increased body burdens are linked to
      increased risk of immunomodulation; and highly exposed and/or susceptible
      subpopulations are at greater risk of toxicological impact.

PMID- 11341074
TI  - Toxicology of metam sodium.
AB  - Metam sodium is the third most commonly used agricultural pesticide (by weight)
      in the U.S. A spill of 19,000 gallons of metam sodium into the Sacramento River
      in 1991 clearly demonstrated that a major uncontrolled release can have adverse
      ecological and human health effects. Furthermore, this incident revealed that
      estimates of Reference Exposure Levels for the major breakdown product of metam
      sodium (methylisothiocyanate, MITC) were reasonable with regard to the induction
      of discomfort. In fact, the irritant properties of MITC seem to account for many
      of the most commonly reported symptoms in this incident. However, neurotoxicity
      may also account for some of these symptoms. There is evidence that metam sodium
      can act as a contact sensitizer in humans, inducing allergic dermatitis. It also
      may exacerbate or induce respiratory allergy (asthma). The ecological impact of
      routine use of metam sodium is not clear, but adverse effects on non-target
      plants have been inferred from modeling studies, and adverse effects on soil
      microbes have been observed. These issues deserve further study. Human health
      effects of occupational or routine environmental exposure to metam sodium are not
      known, but there is limited evidence for immunological (hypersensitivity) and
      developmental effects as well as irritation and associated symptoms. Animal
      studies suggest a potential for immunological, developmental, carcinogenic, and
      atherogenic effects. Metam sodium and some of its breakdown products have a wide
      variety of molecular and cellular actions that could explain the health effects
      noted here. However, further studies are needed to relate specific molecular or
      cellular actions to specific health effects.

PMID- 11341075
TI  - Patient--heal thyself? Electrophysiology meets alternative medicine.

PMID- 11341076
TI  - Clinical value of electrocardiographic parameters in genotyped individuals with
      familial long QT syndrome.
AB  - Rate corrected QT interval (QTc) and QT dispersion (QTd) have been suggested as
      markers of an increased propensity to arrhythmic events and efficacy of therapy
      in patients with long QT syndrome (LQTS). To evaluate whether QTc and QTd
      correlate to genetic status and clinical symptoms in LQTS patients and their
      relatives, ECGs of 116 genotyped individuals were analyzed. JTc and QTc were
      longest in symptomatic patients (n = 28). Both QTd and JTd were significantly
      higher in symptomatic patients than in asymptomatic (n = 29) or unaffected family
      members (n = 59). The product of QTd/JTd and QTc/JTc was significantly different
      among all three groups. Both dispersion and product put additional and
      independent power on identification of mutation carriers when adjusted for sex
      and age in a logistic regression analysis. Thus, symptomatic patients with LQTS
      show marked inhomogenity of repolarization in the surface ECG. QT dispersion and
      QT product might be helpful in finding LQTS mutation carriers and might serve as
      additional ECG tools to identify asymptomatic LQTS patients.

PMID- 11341077
TI  - Implantation of a dual chamber pacing and sensing single pass defibrillation
      lead.
AB  - Dual-chamber ICDs are increasingly used to avoid inappropriate shocks due to
      supraventricular tachycardias. Additionally, many ICD patients will probably
      benefit from dual chamber pacing. The purpose of this pilot study was to evaluate
      the intraoperative performance and short-term follow-up of an innovative single
      pass right ventricular defibrillation lead capable of bipolar sensing and pacing
      in the right atrium and ventricle. Implantation of this single pass right
      ventricular defibrillation lead was successful in all 13 patients (age 63 +/- 8
      years; LVEF 0.44 +/- 0.16; New York Heart Association [NYHA] 2.4 +/- 0.4,
      previous open heart surgery in all patients). The operation time was 79 +/- 29
      minutes, the fluoroscopy time 4.7 +/- 3.1 minutes. No perioperative complications
      occurred. The intraoperative atrial sensing was 1.7 +/- 0.5 mV, the atrial pacing
      threshold product was 0.20 +/- 0.14 V/ms (range 0.03-0.50 V/ms). The
      defibrillation threshold was 8.8 +/- 2.7 J. At prehospital discharge and at 1
      month and 3-month follow-up, atrial sensing was 1.9 +/- 0.9, 2.1 +/- 0.5, and 2.7
      +/- 0.6 mV, respectively, (P = NS, P < 0.05, P < 0.05 to implant, respectively),
      the mean atrial threshold product 0.79, 1.65, and 1.29 V/ms, respectively. In two
      patients, an intermittent exit block occurred in different body postures. All
      spontaneous and induced ventricular arrhythmias were detected and terminated
      appropriately. Thus, in a highly selected patient group, atrial and ventricular
      sensing and pacing with a single lead is possible under consideration of an
      atrial pacing dysfunction in 17% of patients.

PMID- 11341078
TI  - Clinical utility of intraatrial pacemaker stored electrograms to diagnose atrial
      fibrillation and flutter.
AB  - The purpose of this study was to determine if intraatrial electrograms (EGMs) are
      required to diagnose specific types of atrial tachyarrhythmias detected by
      pacemaker diagnostics. DDD pacemakers in 56 patients were programmed to store
      episodes of atrial tachyarrhythmias. Some episodes had a stored atrial EGM
      snapshot of the atrial tachyarrhythmia. The EGMs were analyzed to confirm whether
      the stored episodes were true atrial tachyarrhythmias or other pacemaker-sensed
      events. EGM confirmation of atrial tachyarrhythmias correlated with increasing
      duration and rate of episodes. In particular, using EGMs, 8 (18%) of 44 episodes
      < 10 seconds in duration confirmed atrial tachyarrhythmias compared to 16 (89%)
      of 18 episodes > 5 minutes in duration (P < 0.001). Only 10 (18%) of 56 detected
      atrial arrhythmia episodes at rates < 250 complexes per minute were confirmed by
      the atrial EGM as true arrhythmias compared to 33 (57%) of 58 detected episodes
      at rates > 250/min (P < 0.001) Twenty-nine (91%) of 32 EGM confirmed episodes of
      atrial fibrillation/flutter had an atrial rate > 250 complexes per minute and
      were a minimum of 10 seconds in duration. Fifteen (88%) of 17 episodes meeting
      the combined stored data criteria of > 250 complexes per minute and duration > 5
      minutes were confirmed as atrial fibrillation or flutter by stored EGMs. Atrial
      EGMs identified that 71 (62%) of 114 stored high atrial rate (HAR) episodes were
      events other than true atrial tachyarrhythmias. Pacemaker diagnostic data with
      intraatrial EGMs can diagnose specific atrial tachyarrhythmias and identify other
      pacemaker-sensed events. Stored episodes > 250 complexes per minute and > 5
      minutes in duration had a high correlation with atrial fibrillation and flutter.

PMID- 11341079
TI  - Safety and efficiency of pulse charge multiplication for chronic ventricular
      output programming.
AB  - Fifty-one patients with Intermedics pacemakers and different chronic (> or = 12
      months) ventricular lead models were investigated. Ventricular charge thresholds
      (microC) were measured telemetrically at 1.0, 2.0, 2.5, and 3.5 V, respectively.
      Then pulse duration was increased until charge per pulse (microC) was twice the
      threshold value in patients not being pacemaker dependent (n = 39) and three
      times the threshold in pacemaker dependent patients (n = 12), thus giving a 2:1
      or 3:1 safety factor in terms of charge ("safety charge"). At safety charge
      settings, the battery current was measured telemetrically for all four pulse
      amplitudes (PA) in VVI mode at 70 beats/min. For safety purposes, only pulse
      amplitudes were considered that fulfilled two conditions: (1) pulse duration
      threshold (PDT) < or = 0.30 ms at PA and (2) PDT < or = 1.00 ms at a pulse
      amplitude of (PA-0.5 V). The combination of pulse amplitude and pulse duration
      that yielded the safety charge at the lowest battery current was defined as
      optimized ventricular output (Copt). It was found at 1.0 V in 27 patients and at
      2.0 V in 24 patients. The safety pulse duration (SPD) that yielded a 2:1 safety
      charge in patients who were not pacemaker dependent was 0.32 +/- 0.12 ms for
      both, 1.0 V (n = 23) and 2.0 V (n = 16), respectively. In pacemaker dependent
      patients, the SPD for the 3:1 safety charge was 0.61 +/- 0.25 ms (at 1.0 V, n =
      4) and 0.47 +/- 0.11 ms (at 2.0 V, n = 8), respectively. The safety factor for
      conversion of PDT into SPD was 3.15 (range 3.00-3.38) for pacemaker dependent
      patients and 2.04 (range 2.00-2.43) for patients who were not pacemaker
      dependent, respectively. Charge thresholds measured at study entrance, after 24
      hours, and again after 6 months showed a median variation of 14% and a maximum
      individual variation of 55%. On day 0 and 180, 24-hour Holter recordings were
      obtained from all patients and revealed constant ventricular capture at output
      settings Copt. When the output was changed from a fixed setting (2.5 V at 0.50
      ms) to Copt, the battery current decreased by 17.5% (P < 0.0001). In conclusion,
      pacing thresholds in patients with chronic ventricular leads are stable enough to
      permit programming battery-saving low output settings, if pacemakers are followed
      on a regular basis. Titration of a 2:1 safety charge (a 3:1 safety charge in
      pacemaker dependent patients) by prolongation of pulse duration is safe, provided
      that pulse amplitude is chosen carefully. Using this approach, current
      consumption can significantly be reduced without jeopardizing patient's life.

PMID- 11341080
TI  - Single catheter determination of local electrogram prematurity using simultaneous
      unipolar and bipolar recordings to replace the surface ECG as a timing reference.
AB  - Bipolar recordings eliminate much of the far-field signal, while minimally
      filtered unipolar recordings contain substantial far-field signal components.
      These properties may allow the onset of the unipolar recording to serve as a
      timing reference for the bipolar recording obtained from the same electrode
      catheter during mapping of focal atrial or ventricular tachycardias. Mapping and
      RF ablation were performed in 26 patients with focal ventricular tachycardia and
      14 patients with focal atrial tachycardia. At 205 mapping sites, simultaneous
      recordings of (1) minimally filtered unipolar electrograms (0.5-500 Hz), (2) high
      pass filtered unipolar electrograms (100 Hz), and (3) filtered bipolar recordings
      (30-500 Hz) were analyzed. The interval between the onset of the minimally
      filtered unipolar electrogram and the first peak of the bipolar electrogram
      (UniOn-BiP) correlated closely with the timing of the local electrogram
      referenced to the surface ECG (r = 0.85, P < 0.001). Of 53 sites where RF
      ablation was performed, UniOn-BiP was shorter at successful compared to
      unsuccessful sites (3.8 +/- 3.5 vs 9.2 +/- 5.2 ms, P < 0.001) and was < 15 ms at
      all successful sites. In conclusion, the comparison of simultaneous unipolar and
      bipolar electrograms from a single catheter allows assessment of the prematurity
      of local electrograms from a focal source without the use of the P wave or QRS
      onset as a timing reference.

PMID- 11341081
TI  - Adenosine induced ventricular arrhythmias in the emergency room.
AB  - While adenosine effectively terminates most supraventricular tachycardias (SVT),
      rare case reports have demonstrated its proarrhythmic potential, including
      induction of ventricular tachycardia (VT). The aim of this study was to define
      the proarrhythmic effects of adenosine in a large, unselected population. During
      a 5-year period, adenosine was used (average dose 9.7 mg) in the emergency room
      to manage 187 episodes of tachycardia in 127 patients. In two thirds of the
      cases, adenosine induced ventricular ectopy following successful termination of
      SVT, including premature ventricular complexes (PVC) and nonsustained VT. The
      adenosine induced PVCs and VT were transient and self-terminating. More than half
      had a right bundle branch block morphology with a superior axis that suggested an
      origin in the inferior left ventricular septum. In conclusion, although adenosine
      is commonly used in clinical practice to treat SVTs, we found that it induced
      PVCs and VT in two thirds of the patients. The high incidence of ventricular
      arrhythmias following adenosine infusion was surprising but did not require
      further intervention. These arrhythmias appeared to frequently originate from the
      inferior left ventricular septum, suggesting that this area may be particularly
      susceptible to the proarrhythmic effects of adenosine.

PMID- 11341082
TI  - Prospective randomized comparison of the safety and effectiveness of placement of
      endocardial pacemaker and defibrillator leads using the extrathoracic subclavian
      vein guided by contrast venography versus the cephalic approach.
AB  - The purpose of this prospective randomized study was to compare the safety and
      efficacy of the cephalic approach versus a contrast-guided extrathoracic approach
      for placement of endocardial leads. Despite an increased incidence of lead
      fracture, the intrathoracic subclavian approach remains the dominant approach for
      placement of pacemaker and implantable defibrillator leads. Although this
      complication can be prevented by lead placement in the cephalic vein or by lead
      placement in the extrathoracic subclavian or axillary vein, these approaches have
      not gained acceptance. A total of 200 patients were randomized to undergo
      placement of pacemaker or implantable defibrillator leads via the contrast-guided
      extrathoracic subclavian vein approach or the cephalic approach. Lead placement
      was accomplished in 99 of the 100 patients randomized to the extrathoracic
      subclavian vein approach as compared to 64 of 100 patients using the cephalic
      approach. In addition to a higher initial success rate, the extrathoracic
      subclavian vein medial approach was determined to be preferable as evidenced by a
      shorter procedure time and less blood loss. There was no difference in the
      incidence of complications. In conclusion, these results demonstrate that lead
      placement in the extrathoracic subclavian vein guided by contrast venography is
      effective and safe. It was also associated with no increased risk of
      complications as compared with the cephalic approach. These findings suggest that
      the contrast-guided approach to the extrathoracic portion of the subclavian vein
      should be considered as an alternative to the cephalic approach.

PMID- 11341083
TI  - Incidence of electromagnetic interference in implantable cardioverter
      defibrillators.
AB  - Electromagnetic interference (EMI) with ICDs can lead to temporary inhibition of
      the device or to inappropriate delivery of antitachycardia pacing and shocks. The
      incidence of interactions between electronic devices and the current generation
      of ICDs is not known. In a retrospective study of 341 patients (665 patient
      years) who underwent a regular follow-up every 3 months, five episodes of EMI
      were detected in four different patients. The risk for receiving inappropriate
      shocks due to EMI is < 1% per year and patient. In conclusion, although
      inappropriate delivery of shocks by ICDs due to EMI rarely occurs, patient
      information should emphasize the avoidance of situations of possible
      interference. Further efforts concerning lead technology and detection algorithms
      are necessary to minimize the risk of EMI.

PMID- 11341084
TI  - A cephalic vein cutdown and venography technique to facilitate pacemaker and
      defibrillator lead implantation.
AB  - The aim of this study was to assess the feasibility of a cephalic vein cutdown
      and venography technique for implantation of a pacemaker or ICD and to determine
      the causes of failure of cephalic vein cutdown. In consecutive patients who
      underwent pacemaker or ICD implants, a modified cephalic vein guidewire technique
      was performed. This technique was attempted in 289 pacemaker implants and 26 ICD
      implants (155 men, 160 women; mean age 74 +/- 10 years). The success rate for
      implantation of a single chamber and a dual chamber device by using this
      technique alone was 84% (54/64) and 74% (185/251), respectively (P = 0.10). In an
      additional 7% of patients with dual chamber implant, the cephalic vein can be
      used for passage of the ventricular lead. A cephalic venogram was required in 82
      patients and facilitated the passage of the guidewire in 62 (79%) of them. No
      complication related to vascular access was observed with this technique. This
      technique failed in 54 (17%) of 315 patients due to (1) failure of cephalic vein
      isolation (48%), (2) venous stenosis (24%), or (3) venous torturosity or
      anomalies (28%). There were no significant differences in the patient's age, sex,
      type of device, and the fluoroscopic time for lead placement between patients
      with or without successful lead placement using this technique (all P > 0.05). In
      conclusion, a simple modification of the cephalic vein guidewire technique
      together with venography has facilitated the placement of leads during pacemaker
      and ICD implant. This technique is safe and applicable in the majority of
      patients and avoids the risk of subclavian puncture.

PMID- 11341085
TI  - Spontaneous, electrically, and cesium chloride induced arrhythmia and
      afterdepolarizations in the rapidly paced dog heart.
AB  - Despite frequent arrhythmia and sudden death in heart failure, attempts to study
      arrhythmia mechanisms in patients are difficult. The dog heart, paced for several
      weeks at a fast rate to induce heart failure is prone to arrhythmia. The aim of
      this study was to determine the activation patterns of spontaneous and
      electrically induced arrhythmia and the susceptibility of the failing dog heart
      to arrhythmia and early afterdepolarization (EAD) induced triggered activity
      elicited by exogenous administration of cesium chloride (CsCl). The hearts of 56
      mongrel dogs were paced at 240 beats/min for 3-5 weeks (heart failure group).
      Twenty-one similarly operated, but not paced dogs served as the control group. At
      baseline, all dogs were healthy as assessed electrophysiologically and
      hemodynamically. Spontaneous (bradycardia, tachycardia, and arrhythmic deaths)
      and electrically induced arrhythmia was frequent in dogs with heart failure.
      Also, the minimal dose of CsCl that produced ventricular tachycardia was
      significantly lower in the heart failure than the control dogs (1.02 +/- 0.02 vs
      1.21 +/- 0.07 mMol/kg, P < 0.05). Epicardial mapping during spontaneous and
      electrically induced arrhythmia in the heart failure dogs showed initiation
      patterns with focal origin, often from multiple sites. This pattern was
      consistent with the patterns observed with CsCl induced ventricular tachycardia.
      In in vitro microelectrode studies, CsCl superfusion (2.5-5 mMol/L) induced
      triggered activity due to EADs within 30 minutes, in seven of the eight Purkinje
      fibers from four heart failure dogs. EADs were also found in ventricular myocytes
      of papillary muscle from two heart failure dogs. In contrast, 5 mMol/L CsCl
      induced EADs in only one of eight Purkinje fibers from the hearts of four control
      dogs and no papillary myocytes even with continuous superfusion for up to 60
      minutes (P < 0.01). These results demonstrate that pacing induced heart failure
      in the dog has an increased tendency to develop ventricular tachycardia and
      triggered activity unmasked by CsCl.

PMID- 11341086
TI  - Left atrial- and left ventricular-based single lead DDD pacing.
AB  - Single lead physiological pacing with right ventricular apex stimulation is
      feasible in patients with normal sinus node function and is associated with lower
      costs and a reduced complication rate. Left ventricular or biventricular pacing
      using the tributaries of the coronary sinus was reported to improve functional
      status and quality-of-life in patients with advanced congestive heart failure and
      intraventricular conduction delays. In addition, the proximal part of the
      coronary sinus has been successfully used for left atrial stimulation. The
      feasibility and pacing characteristics of left atrial- and left ventricular-based
      temporary pacing using a conventional single pass lead were studied. The tip of
      the lead was advanced in a distal position of the lateral or posterolateral
      branches of the coronary sinus, providing a stable position of the middle and
      proximal electrode pair in the first 2-7 cm of the coronary sinus. A successful
      stable position was achieved in 13 of 21 consecutive attempts. Using overlapping
      biphasic (OLBI) stimulation, left atrial and left ventricular pacing threshold
      were 2.3 +/- 0.6 and 2.5 +/- 0.5 V, respectively. Acceptable sensing values were
      measured for P waves (4.1 +/- 0.7 mV) and R waves (9.7 +/- 3.9 mV). There was a
      good correlation between the diameter of the coronary sinus as assessed by
      quantitative coronary angiography at the level of the middle and proximal rings
      and atrial pacing threshold (r = 0.92, P < 0.0001). Thus, single lead left atrial
      and left ventricular-based pacing is feasible although further development is
      necessary to increase the success rate for stable stimulation at both sites.

PMID- 11341087
TI  - Interference with cardiac pacemakers by magnetic resonance imaging: are there
      irreversible changes at 0.5 Tesla?
AB  - The safety and feasibility of magnetic resonance imaging (MRI) in patients with
      cardiac pacemakers is an issue of gaining significance. The effect of MRI on
      patients' pacemaker systems has only been analyzed retrospectively in some case
      reports. Therefore, this study prospectively investigated if MRI causes
      irreversible changes in patients' pacemaker systems. The effect of MRI at 0.5
      Tesla on sensing and stimulation thresholds, lead impedance and battery voltage,
      current, and impedance was estimated during 34 MRI examinations in 32 patients
      with implanted pacemakers. After measurements at baseline and with documentation
      of intrinsic rhythm and modification of the pacing mode, patients underwent MRI.
      The rest of the function time of the pacemaker was calculated. Measurements were
      again performed after 99.5 +/- 29.6 minutes (mean +/- SD), immediately after MRI
      examination, and 3 months later. Lead impedance and sensing and stimulation
      thresholds did not change after MRI. Battery voltage decreased immediately after
      MRI and recovered 3 months later. Battery current and impedance tended to
      increase. The calculated rest of function time did not change immediately after
      MRI. MRI affected neither pacemaker programmed data, nor the ability to
      interrogate, program, or use telemetry. Surprisingly, in the gantry of the
      scanner, temporary deactivation of the reed switch occurred in 12 of 32 patients
      when positioned in the center of the magnetic field. Missing activation of the
      reed switch through the static magnetic field at 0.5 Tesla is not unusual. MRI at
      0.5 Tesla does not cause irreversible changes in patients' pacemaker systems.

PMID- 11341088
TI  - Effect of the atrial blanking time on the detection of atrial fibrillation in
      dual chamber pacing.
AB  - Patients with paroxysmal atrial fibrillation (PAF) and dual chamber pacemakers
      frequently have short postventricular atrial blanking times and sensitive atrial
      sensing thresholds used to provide reliable detection and mode switching during
      AF. However, short atrial blanking times increase the risk of atrial sensing of
      ventricular far-field signals. We evaluated if the length of the atrial blanking
      time influences the detection of AF. The study included ten patients with a VDDR
      (n = 7) or DDDR system (n = 3), who presented with AF at 18 follow-up visits.
      Bipolar atrial sensing was programmed to the most sensitive value. Atrial
      blanking times were programmed from 100 to 200 ms in 25-ms steps in each patient.
      Using marker annotation, the following parameters were measured at ten
      consecutive ventricular beats: VAF = the interval between ventricular stimulus
      and first sensing of AF; AFS = the number of atrial-sensed events between two
      ventricular events; and XAF = the interpolated number of atrial-sensed events
      during atrial blanking time. The intervals between ventricular events and between
      atrial-sensed event markers showed no significant differences for the five
      blanking times tested. There was no significant influence of the atrial blanking
      time onto the measured parameters (least square means +/- standard error) with
      VAF between 281 +/- 12 and 300 +/- 12 ms (P = NS), AFs between 3.4 +/- 0.2 and
      3.6 +/- 0.2 beats (P = NS) and XAF between 1.84 +/- 0.12 and 2.03 +/- 0.12 beats
      (P = NS). At ventricular rates < 100/min, the atrial sensing of AF in dual
      chamber pacemakers demonstrated no evidence for deterioration by an increase of
      the atrial blanking time from 100 to 200 ms. Thus, the risk of ventricular far
      field sensing may be reduced without compromising atrial sensing.

PMID- 11341089
TI  - Clinical use of intracardiac impedance: current applications and future
      perspectives.
AB  - For over 40 years the measurement of intracardiac impedance has been proposed as
      a method of assessing the contractile state of the heart muscle. This technique
      requires the positioning of one or more intracavitary electrodes and the
      generation of an electric field from an alternating current source. Variations in
      the calculated impedance signal reflect changes in the ventricular blood pool
      volume adjacent to the electrodes. Intracardiac impedance measurement has been
      successfully developed as a research tool to assess myocardial contractility, and
      from this, clinical uses have evolved. Commercial rate responsive pacing systems
      use intracardiac impedance to assess the inotropic state of the heart. Further
      development of this technology might allow hemodynamic discrimination of cardiac
      arrhythmias.

PMID- 11341090
TI  - Left atrial to right ventricular bidirectional accessory pathway in a patient
      with Ebstein's anomaly: how does it connect?

PMID- 11341091
TI  - Twenty-seven-year follow-up of arrhythmogenic right ventricular dysplasia.
AB  - This case report describes clinical features, especially of surface ECG changes,
      observed for 27 years in a patient with arrhythmogenic right ventricular
      dysplasia (ARVD). The course of this patient was characterized by progressive
      deterioration of right ventricular function and progression of delayed potentials
      (so-called epsilon waves) following QRS complexes. However, the relation between
      ventricular arrhythmias and ECG changes or the degree of right ventricular
      abnormality was difficult to discern.

PMID- 11341092
TI  - Dual AV nodal pathway physiology after injury with radiofrequency energy in a
      patient without a history of reentrant tachycardia.
AB  - Radiofrequency (RF) atrioventricular (AV) nodal modification has been reported to
      occasionally produce a proarrhythmic effect. Dual AV nodal pathway physiology in
      patients without reentrant tachychardia has also been reported. This case
      describes AV nodal modification with RF energy in an anatomically intermediate
      area resulting in the appearance of discontinuous antegrade conduction curves and
      reentry in a patient in which these were previously not present. This suggests
      that AV nodal injury may be a mechanism for acquired AV nodal reentry.

PMID- 11341093
TI  - Polymorphic ventricular tachycardia in a woman taking cesium chloride.
AB  - A 47-year-old patient presented with syncope and recurrent episodes of
      polymorphic ventricular tachycardia. She had evidence of prolonged QT interval by
      ECG and had been taking cesium as a dietary supplement. Correction of the
      hypokalemia and discontinuation of the cesium resulted in normalization of the QT
      interval during follow-up with no further recurrence of ventricular arrhythmias.
      The use of this drug is potentially hazardous as it may induce fatal ventricular
      arrhythmias.

PMID- 11341094
TI  - ICD malfunction caused by excessive defibrillation charge time.
AB  - A 71-year-old man with a history of myocardial infarction and syncopal
      ventricular tachycardia received an ICD. Progressively, increased defibrillation
      charge times of the ICD were observed. During a fast ventricular tachycardia, the
      patient collapsed. The underlying malfunction could be documented by ICD
      telemetric interrogation. An excessive charge time was recorded causing
      subsequent delayed therapy. The ICD was considered potentially ineffective and
      required a generator exchange. This case report underlines the possible factors
      affecting the ICD charge times. Excessive charge time must be considered as a
      rare, or underestimated, cause of ICD malfunction, requiring generator
      replacement.

PMID- 11341096
TI  - Bradycardia and permanent pacing after bilateral thoracoscopic T2-sympathectomy
      for primary hyperhidrosis.
AB  - A 23-year-old woman with craniofacial hyperhidrosis underwent bilateral
      thoracoscopic T2-sympathectomy. Marked sinus bradycardia with a mean heart rate
      of 49 beats/min by Holter ECG monitoring occurred after the procedure and
      persisted for > 2 years. Normal sinus node function was found by an invasive
      electrophysiological study and unopposed vagotonia after sympathectomy was
      diagnosed. A permanent pacemaker was implanted. Although reduced heart rate is a
      common phenomenon after bilateral dorsal sympathectomy, intractable bradycardia
      with permanent pacing is rare. This patient demonstrates one of the potential
      cardiac complications of bilateral sympathectomy.

PMID- 11341095
TI  - Automatically optimizing pacing output: an excellent idea, but with potentially
      lethal pitfalls.
AB  - AutoCapture (AC) and Ventricular Capture Management (VCM) are pacing algorithms
      that attempt to automatically optimize pacing output, providing consistent
      capture and enhancing device longevity. This report describes potentially serious
      consequences from use of these algorithms. In one pacemaker dependent patient, AC
      malfunction led to failure of ventricular capture. This was fixed with a software
      correction. The potential seriousness of AC malfunction leads to the
      recommendation that this software be downloaded into all susceptible pacemakers.
      In a second patient, VCM malfunction resulted in unnecessary high output pacing.
      Our experience illustrates the need for postmarketing surveillance when embracing
      newer technology.

PMID- 11341097
TI  - Central clinical research issues in electrophysiology: report of the NASPE
      Committee.
AB  - This article contains the results of an attempt by appointed members of the North
      American Society of Pacing and Electrophysiology to define the research frontier
      in electrophysiology and suggest areas of study as an aid in setting the research
      agenda.

PMID- 11341098
TI  - How can we identify the best implantable site for an ECG event recorder?

PMID- 11341099
TI  - The recent study by Wood et al. comparing mode switching algorithms in four
      different Medtronic (Minneapolis, MN, USA) pacemakers.

PMID- 11341100
TI  - Atherosclerosis and autoimmunity.
AB  - Novel risk factors for the progression of atherosclerosis such as C-reactive
      protein (CRP) and adhesion molecules have stimulated much recent interest in the
      role of inflammation in atherosclerotic disease. There is also evidence emerging
      that autoimmunity may have a role in the pathogenesis of atherosclerosis. In this
      article we explore the evidence for the role of autoimmunity in human
      atherosclerosis, both in the general population and in the context of the
      antiphospholipid syndrome. In particular we will focus on several autoantigens,
      review the evidence for their role in the process of atherosclerosis and the
      nature of the immune responses.

PMID- 11341101
TI  - Therapy with pulse methylprednisolone and short course pulse cyclophosphamide for
      diffuse proliferative glomerulonephritis.
AB  - The incidence of renal flares and the long-term outcome in a group of 33 systemic
      lupus erythematosus (SLE) patients with diffuse proliferative glomerulonephritis
      (DPGN) treated with pulse steroids and a short course of pulse cyclophosphamide
      (CYC) are evaluated. Fifteen patients (45%) experienced a flare of renal disease
      at some time after the discontinuation of the immunosuppressive (IS) therapy;
      among these half (24%) were 'early' flares occurring shortly after the
      discontinuation of therapy, and the other half (21%) were 'late' flares occurring
      more than 2 y after the discontinuation of the treatment. Nine patients (27%)
      showed a poor renal outcome at the end of follow-up. On multiple regression
      analysis, a younger age and a high activity index (AI) on renal histology were
      found to be correlated with the occurrence of renal flares. Our results suggest
      that the combination of pulse steroids with a short course of pulse CYC (six to
      nine pulses) is effective in both controlling disease activity and in preventing
      the occurrence of renal flares in DPGN. However, short term IS therapy might not
      be sufficient to maintain disease control in younger patients with active lesions
      on renal histology. Such patients might be candidates to receive more prolonged
      IS treatment.

PMID- 11341102
TI  - Antioxidants suppress mortality in the female NZB x NZW F1 mouse model of
      systemic lupus erythematosus (SLE).
AB  - Inflammation produces reactive oxygen intermediates (ROI) that cause vascular
      damage and activate T lymphocytes. Conversely, antioxidants not only protect
      tissue from oxidative damage but also suppress immune reactivity. The objective
      of this study was to examine immunomodulatory effects of the non-enzymatic
      antioxidants, N-acetylcysteine (NAC) and cysteamine (CYST), on autoimmune
      disease, glomerulonephritis, and mortality in the female B/W mouse model of human
      systemic lupus erythematosus (SLE). The development of murine lupus was assessed
      during the lifespan of female B/W mice given NAC or CYST. Morbidity and mortality
      were assessed daily. At 6 week intervals mice were examined for weight change,
      albuminuria, serum BUN, antibodies to DNA, and IgG immunoglobulin levels. Serum
      prolactin, estrogen and progesterone were measured at 18 weeks of age. In a
      parallel study, NAC- and CYST-treated and control B/W mice were examined at 24
      weeks of age for interval renal histopathology, lymphocyte adhesion molecule
      expression, and antibody titers and in vitro cytokine production in response to
      immunization with DNP-KLH. CYST significantly suppressed development of
      albuminuria and azotemia at 36 and 42 weeks of age compared to control and NAC
      treated mice. NAC significantly suppressed anti-DNA antibody levels at 24 weeks.
      In contrast CYST significantly increased anti-DNA antibody levels at 18 weeks of
      age (P < 0.001 CYST vs control and NAC-treated mice). Kidneys of CYST-treated
      mice also had accelerated inflammatory histologic changes despite their lower
      incidence of albuminuria and azotemia. Mean (+/- s.e.m.) survival of control mice
      was 33 +/- 2 weeks compared to 38 +/- 2 weeks in NAC-treated mice (P < 0.05 vs
      control), and 48 +/- 2 weeks in the CYST-treated group (P < 0.01 vs control
      mice). The antioxidants, NAC and CYST, significantly improved mortality in the
      female B/W mouse model of SLE. NAC suppressed autoantibody formation and modestly
      prolonged survival. CYST, despite its augmentation of anti-DNA levels and renal
      inflammatory changes, inhibited the development of renal insufficiency and
      markedly improved survival. These findings suggest that ROIs play a role in the
      pathogenesis of lupus nephritis and that antioxidants reduce the damage causing
      renal insufficiency. Antioxidants may be a beneficial adjunctive therapy in the
      treatment of human SLE.

PMID- 11341103
TI  - Assessing depression in systemic lupus erythematosus: determining reliable
      change.
AB  - Systemic lupus erythematosus (SLE) can follow an unpredictable course. Clinicians
      and researchers use various self-report inventories to track aspects of the
      patient's functioning during the course of the illness (e.g. health status, pain,
      fatigue, quality of life and psychological status). These self-report inventories
      are used to measure improvement or deterioration as a function of the natural
      history of the disease process, or as a function of response to treatment. Proper
      interpretation of scores derived from these inventories requires an understanding
      of their psychometric properties, in particular, their reliability. It is
      important to calculate reliable change difference scores for tests commonly used
      in rheumatology so clinicians can determine if a change score is a reliable
      indicator of improvement or deterioration in individual patients (i.e. the change
      score is not likely to be due to measurement error). The purpose of this article
      is to illustrate the use of the reliable change difference scores when assessing
      depression in patients with SLE using the Beck Depression Inventory (BDI).

PMID- 11341104
TI  - In vitro ultraviolet irradiation induces pro-inflammatory responses in cells from
      premorbid SLE mice.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disease, in
      which sunlight (especially its ultraviolet radiation (UVR)) is known to induce
      exacerbation of cutaneous lesions as well as systemic manifestations of the
      disease. The aim of this in vitro study was to investigate whether UVR (UVA, UVB)
      amplifies pro-inflammatory factors in cultured dermal fibroblasts (DF) or lymph
      node cells derived from premorbid or morbid mice from the murine SLE strains (MRL
      1pr/1pr, (NZB/NZW)F1), in comparison to cells derived from normal mice from the
      non-SLE strains (C57BL/6, BALB/c). Our results demonstrate the following. Dermal
      fibroblast of premorbid SLE mice showed increased susceptibility to UVA and UVB
      irradiation, determined by viability assay, in comparison to those of normal
      mice. UVB irradiation induced an enhanced expression of ICAM-1 in such SLE
      derived cells, in comparison to cells of normal mice. UVA and UVB increased
      functional activity of LFA-1 in lymph node cells of premorbid SLE mice and not in
      normal controls. UVB irradiation induced increased production and secretion of
      pro-inflammatory cytokines (IL-1, IL-6, TNF-alpha) in DF of premorbid SLE mice,
      in comparison to normal controls. The enhanced pro-inflammatory responses to UVR
      were also observed in experiments conducted with cells derived from morbid SLE
      mice. In conclusion, the pro-inflammatory proneness detected in the premorbid
      stage of murine SLE could be of major importance in SLE pathogenesis.
      Furthermore, it suggests that the autoimmune inflammatory process in vivo,
      triggered initially by immune complex deposition, could be further amplified by
      UVR.

PMID- 11341105
TI  - A possible role of apoptosis for regulating autoreactive responses in systemic
      lupus erythematosus.
AB  - It has been reported that apoptotic cells are increased in the peripheral blood
      from patients with systemic lupus erythematosus (SLE), where dysfunctions of T
      helper 1 (Th1) cells are known. In order to study whether apoptosis of Th1 cells
      is associated with the pathogenesis of SLE, early apoptotic cells in various T
      cell subsets were detected using fluorescence-labeled annexin V (AnV). AnV
      binding was most frequently observed in CD4+CCR5+ T cells, and AnV binding rate
      (%) in this subset was higher in SLE than in normal controls (14.7 +/- 2.6),
      although that in active SLE (43.6 +/- 7.3) tended to be lower than that in
      inactive SLE (48.0 +/- 6.8). CD95/Fas expression was also increased in both
      active and inactive SLE. In some SLE patients, AnV binding rate changed in
      inverse proportion to titer of the serum anti-DNA antibody and in proportion to
      serum complement activity. These data suggest that apoptosis in Th1 cells is
      important in the pathogenesis of SLE and might play a role in regulating over
      activation or autoreactive responses by T cells.

PMID- 11341106
TI  - The effects of a human IgM monoclonal anticardiolipin antibody on pregnancy in a
      transgenic mouse model.
AB  - The clinical features of antiphospholipid (or Hughes') syndrome (APS) are most
      commonly seen in individuals who have raised levels of IgG anticardiolipin
      antibodies. Most murine models of the syndrome have involved the administration
      of such antibodies to normal mice. However, APS can occur in the presence of
      raised levels of serum IgM anticardiolipin antibodies alone. The present study
      was designed to see if an IgM monoclonal antibody can induce changes in mice
      similar to those seen in human APS. This antibody, BH1, has previously been
      derived from a patient with primary APS. In its ligand-binding and idiotypic
      characteristics it is representative of antiphospholipid antibodies (aPL) found
      in the serum of patients with APS. In order to minimise the immune response to
      human IgM, we used transgenic mice (F15) which express, and are predicted to be
      tolerant of, human immunoglobulin mu chains. The features of APS may develop more
      readily in individuals who have an existing autoimmune disorder, such as systemic
      lupus erythematosus (SLE). We therefore crossed these transgenic mice with New
      Zealand Black (NZB, SLE-prone) mice, and used the progeny (F15 x NZB/F1) in our
      experiments. Twenty-four F15 x NZB/F1 mice were given BH1, or a control IgM
      antibody, (A5566) immediately preceding and then three times during pregnancy.
      There was a reduction in the mean number of foetuses in animals given BH1
      compared with those given A5566 (8.6 vs 11.0; P < 0.05), and a similar reduction
      in mean total foetal weight per pregnancy (9.05 vs 12.73 g; P < 0.05). Two mice
      showed a marked reduction in platelet count. No evidence of thrombosis was
      detected macroscopically or histologically. Our results show a lower incidence of
      APS-type features compared to previous studies in which mice have been
      administered aPL. This may be because BH1 is an IgM antibody. Nevertheless, the
      data support the concept that IgM aPL of particular ligand-binding specificities
      may have a direct pathogenetic role in certain cases of human APS.

PMID- 11341107
TI  - Severe bone marrow failure associated with the use of alternating steroid with
      chlorambucil in lupus membranous nephropathy in Chinese.
AB  - Severe pancytopenia associated with the use of alternating steroid with
      chlorambucil regimen was described in six patients with nephrotic syndrome
      secondary to lupus membranous nephropathy (WHO class V). We believe this is the
      first report describing the life-threatening degree of marrow toxicity associated
      with this regimen of alternating steroid with chlorambucil in a Chinese
      population. Our data suggests that the susceptibility to marrow toxicity with the
      use of chlorambucil may only be applicable to Chinese patients with underlying
      systemic lupus erythematosus as a similar degree of toxicity has neither been
      reported in lupus patients of other ethnic groups nor in non-lupus patients of
      Chinese origin.

PMID- 11341108
TI  - Lues and lupus: syphilis mimicking systemic lupus erythematosus (SLE).
AB  - Malar rash and photosensitivity are common findings in systemic lupus
      erythematosus (SLE). However, a number of inflammatory, dermatologic, infectious
      or drug-induced conditions may mimic cutaneous findings of SLE. These typically
      include seborrheic dermatitis, contact dermatitis, rosacea, polymorphous light
      eruption, syphilis and dermatomyositis sine myositis. Herein we describe a
      patient with fever, malar rash, alopecia, photosensitivity, arthralgias and
      lymphadenopathy who was subsequently diagnosed with secondary syphilis. In this
      case report we review clinical and histopathological findings in the differential
      diagnosis of malar rash and photosensitivity and discuss the overlapping features
      of syphilis and SLE.

PMID- 11341109
TI  - Life-threatening angioedema in systemic lupus erythematosus.
AB  - Life-threatening angioedema involving the upper respiratory tract is an uncommon
      manifestation in systemic lupus erythematosus (SLE). We report three patients in
      their late adolescence who had laryngeal oedema causing airway obstruction and
      requiring mechanical ventilation during active disease following symptoms of a
      respiratory tract infection. All of them had major organ involvement from lupus
      and none had a family history of hereditary angioedema (HAE). The mechanisms of
      angioedema in SLE are heterogeneous. There has been little evidence so far of
      anti-Cl inhibitor (Cl INH) autoantibody in SLE patients with angioedema. These
      are the first three cases reported in the literature of life-threatening
      angioedema following respiratory tract infection in SLE.

PMID- 11341110
TI  - Cerebral glucose metabolism in Sneddon's syndrome associated with
      antiphospholipid antibodies.

PMID- 11341111
TI  - Lupus anticoagulant--hypoprothrombinemia syndrome and pregnancy.

PMID- 11341112
TI  - Births: final data for 1999.
AB  - OBJECTIVES: This report presents 1999 data on U.S. births according to a wide
      variety of characteristics. Data are presented for maternal demographic
      characteristics including age, live-birth order, race, Hispanic origin, marital
      status, and educational attainment; maternal characteristics (medical risk
      factors, weight gain, tobacco and alcohol use); medical care utilization by
      pregnant women (prenatal care, obstetric procedures, complications of labor
      and/or delivery, attendant at birth, and method of delivery); and infant
      characteristics (period of gestation, birthweight, Apgar score, abnormal
      conditions, congenital anomalies, and multiple births). Also presented are birth
      and fertility rates by age, live-birth order, race, Hispanic origin, and marital
      status. Selected data by mother's State of residence are shown, as well as data
      on month and day of birth, sex ratio, and age of father. Trends in fertility
      patterns and maternal and infant characteristics are described and interpreted.
      METHODS: Descriptive tabulations of data reported on the birth certificates of
      the 3.96 million births that occurred in 1999 are presented. RESULTS: Overall
      birth and fertility rates changed less than 1 percent in 1999. Teenage birth
      rates fell 2 to 6 percent. The rate for women aged 20-24 years declined slightly,
      while rates for women in their late twenties and their thirties rose 2 to 3
      percent each. The number of births to unmarried women, the birth rate, and the
      percent of births that were to unmarried women each rose 1 percent or less.
      Smoking by pregnant women overall dropped again, but rose among women aged 18-24
      years. Improvements in prenatal care utilization continued. The cesarean delivery
      rate increased for the third year after declining for 7 consecutive years. The
      proportion of multiple births continued to rise; however, higher order multiple
      births (e.g., triplets, quadruplets) declined for the first time in over a
      decade, following increases of 13 percent per year during 1990-98. The percent
      low birthweight remained at 7.6 percent, while preterm births rose to 11.8
      percent. These trends are in large part the result of increases in multiple
      births.

PMID- 11341113
TI  - [Proteases and prostatic disease: cytosolic cathepsin D].
AB  - OBJECTIVE: Cytosolic cathepsin D is a recognized predictor in breast cancer. This
      study was conducted to determine its behaviour in benign prostatic hyperplasia
      (BPH) and prostate cancer. The changes according to prostate volume, its relation
      with other serum markers (PSA, PAP, etc.) in regard to tumor grade, stage and
      survival were analyzed. METHODS: The study was carried out on 376 patients with
      prostatic disease that had been diagnosed from 1991-1996. Determination of
      cytosolic cathepsin D levels was performed on all samples of prostate tissue
      according to the CIS BioInternational Immunoradiometric study. RESULTS: Cathepsin
      D values ranged from 0.2 to 86.5 pmol/mg (mean 14.9) in patients with BPH and
      higher values were found for prostates with a larger volume (p = 0.004). A
      significant difference was found between patients with and those without a
      bladder catheter (p = 0.024); values were higher in the former group of patients.
      Cathepsin D values ranged from 0.5 to 74 pmol/mg (mean 18.13) in patients with
      prostate cancer. A statistically significant difference was found between the
      mean values of patients with prostate cancer and those with BPH (p = 0.047). In
      patients with prostate cancer, a significant difference was also found between
      patients with and those without a catheter (p = 0.04). No relationship was found
      between cathepsin D and the other parameters analyzed. CONCLUSIONS: As in most of
      the literature reviewed, cytosolic cathepsin D was not found to be a predictor in
      prostate cancer. Furthermore, no correlation was found between cathepsin D and
      the other markers analyzed. The foregoing may be due to the small number of tumor
      samples and short follow-up.

PMID- 11341114
TI  - [Quality perceived in the care process by patients treated with prostatectomy for
      cancer. Results of a qualitative study].
AB  - OBJECTIVE: To analyze the care process and treatment outcomes from the
      perspective of patients undergoing prostatectomy. METHODS: A qualitative study
      based on depth interviews was performed in 12 of 14 patients who had undergone
      prostatectomy for localized prostate cancer at a regional hospital. An
      intentional survey was carried out. Patients were informed about the survey
      through a letter and by telephone and were asked to decide where they wished the
      interview to be held. All patients were interviewed by one of the authors who was
      unrelated with the hospital. The interviews were recorded and transcribed with
      the patients' consent and the assurance of confidentiality. We performed
      qualitative analysis of the transcriptions, interviewer's notes and patient
      hospital discharge reports, and validation through discussion of the results
      after deleting all identity-related data. RESULTS: Transmission of the care
      process experiences transcends the presumable adequacy to the conventional phases
      of diagnosis, treatment and outcome. Patient assessment varied according to the
      functional results achieved, previous symptoms, patient expectations and
      interpretation of the information provided. Due to this variability, the
      urologist's approach should be individualized to each patient from the outset,
      before the definitive diagnosis is made, and should continue long after surgery.
      In this regard, substantial shortcomings in urologist-patient communication were
      found. CONCLUSIONS: The approach to the perspectives of patients with localized
      prostate cancer is a necessary component that has not been sufficiently developed
      by the urologist during the clinical management of this disease or its subsequent
      assessment. Apart from the changes in attitude that the foregoing may entail, it
      is advisable to incorporate quantitative and qualitative measures that support
      patient assessment of quality of life and its variability, into the daily
      practice of all the health professionals involved.

PMID- 11341115
TI  - [Detubularized ureterosigmoidostomy Mainz II: a diversion with a future?].
AB  - OBJECTIVE: To review the results achieved with the Mainz II detubularized
      ureterosigmoidostomy for urinary diversion in patients undergoing bladder
      resection. METHODS: This study was conducted on 12 prospective patients
      undergoing radical cystectomy for urothelial carcinoma after 1996. All patients
      met the following selection criteria: no changes in upper urinary tract
      functions, normal rectosigmoid, no previous radiation to the area and good anal
      continence. RESULTS: All patients had a diagnosis of infiltrating urothelial
      carcinoma of the bladder. Four of these patients died from tumor progression.
      Renal function is preserved at 31.7 months' mean follow-up, although 3 patients
      developed moderate metabolic acidosis despite the prophylactic alkalization
      therapy instituted after surgery. One patient presented recurrent pyelonephritis
      and stricture of the ureterointestinal anastomosis that required surgical
      correction. Colonoscopy was unremarkable in all but one patient who showed
      adenomatous polyp of the colon, which was removed endoscopically, and no other
      local changes. Continence was complete from the time the urinary catheters were
      removed. Voiding occurred every 2.9 hours during the day and 2.2 times during the
      night. CONCLUSIONS: The Mainz II modified ureterosigmoidostomy clearly reduces
      the upper urinary tract complications because accommodation of the reservoir is
      better and the pressure inside the pouch is reduced. This technique of urinary
      diversion is well-accepted by the patients because voiding can be achieved
      comfortably, a stoma is not required and body image is preserved. The degree of
      patient satisfaction was high in all cases.

PMID- 11341117
TI  - [Urodynamic behavior of intestinal neobladder: our experience].
AB  - OBJECTIVE: To analyze the urodynamic behavior of the intestinal neobladders in
      our series. METHODS: The study comprised 20 patients with a detubularized
      intestinal neobladder. The ileal segment was utilized in 15 (13 Melchior, 1 Camey
      and 1 Padovana), the ileocecal segment in 4 (3 Mainz, 1 Le Bag) and detubularized
      sigmoid in one patient. A urodynamic study was performed in all patients to
      determine neobladder capacity, presence of peristaltic waves, filling and voiding
      pressures, peak and mean urinary flow and postvoid residual urine. The patients
      were also asked about continence, if a collecting device was required and the
      overall degree of satisfaction. RESULTS: Mean neobladder capacity was 508 ml.,
      mean reservoir accommodation was 38 ml/cm H2O and 66.7% presented significant
      peristaltic contractions. Maximum filling pressure was 27 cm H2O. All patients
      showed peaks in the flowmetry due to the abdominal pressure, with a mean maximum
      peak flow of 16.6 ml/sec. Mean postvoid residual urine was 43.6 ml. Eighty
      percent of the patients were continent during the day, 55% were continent during
      the night and 25% were completely continent. All patients used abdominal pressure
      for voiding and generally in the sitting position. The overall degree of
      satisfaction was moderate to high in all but two patients; one required self
      catheterization and the other had frequent interruptions during work due to leaks
      during the day, but refused to use a collecting device. CONCLUSIONS: If renal
      function is preserved and the criteria for radical oncologic treatment are
      observed, substitution of the compromised bladder should be attempted with a
      reservoir as physiological as possible. The ideal continent urinary diversion
      must meet the following prerequisites: adequate capacity, low pressure inside the
      reservoir, absence of pressure waves, continence and absence of postvoid residual
      urine. The mean capacity of the intestinal neobladders in this study, as well as
      the maximum pressure inside the reservoirs were found to be adequate. However,
      many patients presented peristaltic contractions with urinary leaks in some
      cases, and the percentage of patients with residual urine also appears to be
      high. Most of these patients do not require the use of pads during the day, while
      almost all of the patients require some type of collecting device at night for
      incontinence. Nevertheless, the patients in this series were generally satisfied
      with their neobladder.

PMID- 11341116
TI  - [Clinical prognostic factors in superficial cancer of the urinary bladder].
AB  - OBJECTIVE: To determine the relation of the classical prognostic factors (tumor
      stage, grade, size and location) to the recurrence rate, disease free interval
      and overall survival in patients with superficial bladder cancer. METHODS: The
      study was carried out on 144 patients with superficial transitional cell
      carcinoma of the bladder (pTa, pT1) over a period of three years. Age, sex,
      history of exposure to aniline, smoking, histological type, tumor grade, size,
      stage, localization (single vs multiple) and type of complementary treatment were
      analyzed. Tumors were staged according to the TNM classification (1997 version)
      and cell grade was determined according to the Broders classification. RESULTS:
      Mean age was 70 years +/- 12.55 (range 22-100); 124 (86%) were males and 20 (14%)
      were females. All tumors were superficial transitional cell carcinoma; 93% were
      papillary and the remaining 7% were solid tumors. There were 52 recurrences
      (36%); of these, only 13 (25%) showed tumor progression: 4 became infiltrating
      (31%), one (8%) advanced in superficial tumor stage and 8 (61%) advanced in
      grade. Mean follow-up was 31 months (range 3-61). Overall and disease free
      survival at 5 years were 88.42% and 45%, respectively. No differences were found
      for disease free survival according to the different prognostic factors analyzed.
      Tumor grade correlated with stage and size. Thus, grade III tumors are likely to
      be stage pT1 and greater than 3 cm. in size. CONCLUSIONS: The histological grade
      is the most important prognostic factor in bladder cancer progression. However,
      while grade I and III tumors show a rather similar behavior, the moderately
      differentiated tumors comprise a heterogeneous group with a very disparate
      behavior. Tumor grade was found to correlate with stage and size.

PMID- 11341118
TI  - [Analysis of 109 urethroplasties for hypospadias].
AB  - OBJECTIVE: To review our experience in hypospadias surgery in order to determine
      the most appropriate technique for each particular case. METHODS: 109
      uretroplasty procedures for hypospadias repair in 102 patients that were
      performed by the same surgeon from 1992-1998 were analyzed. Eighty-five patients
      were treated for the first time and 17 had previously undergone surgery. The
      patients were children aged 2-12 years and 4 adults. There were 28 balanic, 45
      subcoronal, 10 distal penile, 12 mid penile and 7 penoscrotal hypospadias. Twenty
      two cases had an associated ventral penile curvature. The Magpi technique was
      utilized for the balanic hypospadias, the Mathieu for the subcoronal and distal
      penile hypospadias without curvature, the Duckett technique was utilized for the
      middle penile third and some penoscrotal hypospadias, and the two-stage procedure
      with extragenital free skin graft in some of the cases with penoscrotal
      hypospadias. RESULTS: The overall complication rate was 6.4%. Good results were
      achieved in all patients treated with the Magpi technique. Two patients treated
      with the Mathieu technique developed fistula that was corrected in a second
      procedure, and one patient developed a stricture at 6 years, which required
      another reconstruction procedure. Three patients treated with the Duckett
      technique developed fistula that required another repair procedure. There was one
      case of stricture along the entire length of the graft in the patients treated
      with the two-stage procedure and extragenital free skin graft, and satisfactory
      results were achieved in the remaining patients. CONCLUSIONS: As in any other
      urethroplasty procedure, hypospadias repair requires a correct choice of
      technique for each particular case. Success depends on good tissue
      vascularization, which a surgeon with experience in these techniques can achieve
      better than one that is less experienced. It is therefore advisable not to
      overdiversify.

PMID- 11341119
TI  - [Percutaneous nephropexy].
AB  - OBJECTIVE: To evaluate the efficacy of percutaneous nephropexy in symptomatic
      renal ptosis. METHODS: From August 1997 to September 1999, 6 women aged 28-49
      years (mean 34.3) with symptomatic renal ptosis underwent percutaneous
      nephropexy. All patients were evaluated preoperatively by IVP and diuretic
      renogram in the standing and lying positions. Patient follow-up ranged from 14-34
      months (mean 21). RESULTS: Mean operating time was 30 minutes and mean length of
      hospital stay was 24 hours. Treatment was successful in 5 patients; lumbar pain
      disappeared and the kidney was fixed in a higher position. CONCLUSIONS:
      Percutaneous nephropexy can be an alternative to conventional and laparoscopic
      nephropexy.

PMID- 11341120
TI  - [Medical treatment of uric acid lithiasis of the urinary tract and usefulness of
      double J catheter].
AB  - OBJECTIVE: To analyze the utility of chemolysis and the double-J ureteral
      catheter in patients with uric acid calculi. METHODS: The study comprised 30
      patients (28 men and 2 women) treated with chemolysis for uric acid calculi and
      who consulted for renal colic. The indication for placement of a double-J
      ureteral stent were pain, moderate-to-severe hydronephrosis, fever and urinary
      tract infection. The calculi were < or = 10 mm in size and were located in the
      renal pelvis (3), upper ureter (5), middle ureter (2) and lower ureter (23).
      RESULTS: The uric acid calculi were dissolved with intravenous and oral
      combination chemolysis. The double-J catheter was useful in the cases with
      urinary tract obstruction, fever or urinary tract infection. CONCLUSIONS: Medical
      treatment is useful in the management of uric acid calculi. The double-J catheter
      is beneficial in patients with urinary tract obstruction.

PMID- 11341121
TI  - [Simple syringocele of Cowper's glands].
AB  - OBJECTIVE: To describe an additional case of simple syringocele of Cowper's
      glands and review the literature. METHODS: An additional case of simple
      syringocele of Cowper's glands is presented and the literature over the last 10
      years is reviewed. RESULTS/CONCLUSIONS: The treatment most commonly utilized is
      marsupialization to the urethra by endoscopy. The foregoing was performed in our
      patient with satisfactory results.

PMID- 11341122
TI  - [Transitional cell carcinoma in a young heavy marihuana smoker].
AB  - OBJECTIVE: To report a case of low grade papillary transitional cell carcinoma of
      the left renal pelvis in a young, heavy smoker of marihuana who denied cocaine
      use, alcohol intake and other habits. METHODS/RESULTS: Intravenous pyelogram
      demonstrated a filling defect in the left renal pelvis and calyces. Biopsy
      revealed a urothelial carcinoma. The pathological analysis demonstrated diffuse
      low-grade non-invasive (Ta) papillary transitional cell carcinoma of the renal
      pelvis and calyces. Nephroureterectomy was performed. CONCLUSIONS: This case
      indicates a cause-effect relationship between heavy and long-term marihuna
      smoking and transitional cell cancer. However, further cases from the literature
      or observations in larger populations are warranted.

PMID- 11341123
TI  - [Acute scrotum and Schonlein-Henoch purpura: report of 2 new cases].
AB  - OBJECTIVE: To report two additional cases of Schonlein-Henoch purpura that
      developed acute scrotum. METHODS: Two patients with Schonlein-Henoch purpura that
      developed acute scrotum in the course of the disease are presented. The
      literature is briefly reviewed and discussed. RESULTS/CONCLUSIONS: Schonlein
      Henoch purpura is a systemic vasculitis with involvement of the genital area in
      15% of the cases and must be distinguished from testicular torsion. The clinical
      features, the findings at physical examination and scrotal ultrasound evaluation
      should suffice to make the correct diagnosis and avoid surgery. However, if the
      findings are inconclusive, techniques using isotopes and/or echo-Doppler can be
      utilized. If these are not available, exploratory scrototomy should not be
      delayed. Excellent response is achieved with steroid therapy.

PMID- 11341124
TI  - [Bilobular benign retroperitoneal schwannoma].
AB  - OBJECTIVE: To describe an additional case of retroperitoneal schwannoma. METHODS:
      A case of retroperitoneal neoplasm in a 29-year-old woman is presented. The
      clinical and therapeutic aspects are discussed. RESULTS: The anatomopathological
      study showed a benign schwannoma. CONCLUSIONS: Retroperitoneal schwannoma is an
      uncommon lesion that is difficult to diagnose preoperatively. Treatment is by
      surgical resection.

PMID- 11341126
TI  - [Idiopathic retroperitoneal fibrosis].
AB  - OBJECTIVE: A case of idiopathic retroperitoneal fibrosis in a 34-year-old man
      with anemia and elevated erythrocyte sedimentation rate is presented.
      METHODS/RESULTS: Ultrasound, CT and MRI evaluation and pathological study were
      performed. These diagnostic imaging techniques demonstrated an infiltrating mass
      in the upper portion of the abdomen which was resected. Histological and
      immunohistochemical studies of the surgical specimen demonstrated sclerosing
      retroperitonitis. CONCLUSIONS: Idiopathic retroperitoneal fibrosis (Ormond's
      disease) is a rare disease entity whose etiology is obscure and is characterized
      by retroperitoneal fibrosis with inflammatory infiltrates composed of plasma
      cells, lymphocytes and eosinophils. This case is of interest due to its atypical
      location, and because the patient was young with no remarkable clinical history
      and only mild anemia and an elevated erythrocyte sedimentation rate.

PMID- 11341125
TI  - [Adrenal gland pseudocyst: 2 cases manifesting with acute abdominal pain and
      shock].
AB  - OBJECTIVE: To describe two cases of adrenal pseudocyst that presented as acute
      abdomen and shock. METHODS: Two cases of adrenal pseudocyst are presented: one
      patient was a 69-year-old woman who presented with shock and pain in the left
      hypochondrium and the other was a 23-year-old woman who complained of dizziness
      and pain in the left hypochondrium. RESULTS: US and CT evaluation showed a
      heterogeneous cystic mass. Blood analysis showed low hematocrit and hemoglobin
      levels. Surgical resection of the retroperitoneal cystic mass was performed. The
      pathological analysis disclosed an adrenal pseudocyst. CONCLUSIONS: Adrenal
      pseudocyst is an uncommon lesion that infrequently causes symptoms and rarely
      presents as acute abdomen. Ultrasound and CT are the most useful diagnostic
      imaging methods. Treatment is by surgery if the lesion is large and symptomatic,
      if it cannot be clearly distinguished from a tumor, and if massive hemorrhage
      occurs.

PMID- 11341127
TI  - [Nephritic colic caused by periureteral fibrosis resulting from metastasis from
      lobular carcinoma of the breast].
AB  - OBJECTIVE: To report a rare case of renoureteral colic in a patient with a
      solitary left kidney, due to fibrosis around the renal pelvis and ureter from
      metastatic lobular carcinoma of the breast. METHODS/RESULTS: A 45-year-old
      patient consulted at the emergency services for pain in the left renal fossa that
      irradiated to the genital organs. Patient evaluation showed lid edema and
      oliguria. An abdominal ultrasound scan demonstrated left hydronephrosis. The
      cause of the obstruction could not be determined by imaging techniques.
      Exploratory lumbotomy was performed and the pelvis and ureter were released from
      the fibrotic covering. The histological analysis showed infiltration of the
      ureteral adventitia arising from lobular breast carcinoma. CONCLUSIONS:
      Retroperitoneal metastases that cause ureteral obstruction usually occur two
      years following diagnosis of the primary tumor. This is one of the few cases of
      ureteral obstruction from metastatic lobular carcinoma of the breast reported in
      the literature. Unlike the other cases, however, our patient showed a complicated
      genitourinary malformation.

PMID- 11341129
TI  - [Ethics and medicine].

PMID- 11341128
TI  - Apoptotic regression of prostatic tissue induced by short-term doxazosin
      treatment in benign prostatic hyperplasia.
AB  - OBJECTIVES: Benign enlargement of the prostate comprises both hypertrophy and in
      particular hyperplasia of prostatic stromal and glandular compartments. Alpha
      adrenergic blockade has been shown to be effective in the management of BPH.
      Recent investigations have shown that this effect may in part be due to
      apoptosis. METHODS: A total of 29 patients who were symptomatic due to BPH were
      enrolled into this prospective placebo controlled, double-blind randomized study
      and underwent prostatectomy at the end of the 4th week. Clinical efficacy was
      evaluated by a set of detailed investigations. Surgical specimens were analyzed
      by immunohistochemistry and tissue components of stroma, smooth muscle and
      glandular epithelium were calculated by a software on a computer after
      representative areas were scanned and captured as high resolution images.
      Apoptosis in each tissue specimen was analyzed by Terminal Deoxynucleotidyl
      Transferase End Labelling (TUNEL) method utilizing Biotin-16-dUTP. RESULTS: Both
      groups were similar in terms of baseline evaluation in all aspects. There was a
      steady decline in patients' urinary complaints as evidenced by International
      Prostate Symptom Score System (IPSS) in the doxazosin group compared to placebo.
      Uroflowmetric investigations on patients revealed that maximum flow rates in the
      active drug group increased throughout the study. Mean PSA levels decreased by
      14% at the end of the study in the doxazosin group, while it increased by 11% in
      the placebo group. Average stroma to epithelial ratio in the doxazosin group was
      2:1 in comparison to a value of 1:1 in the placebo group. The rate of apoptosis
      was 2.2% and 3.2% for the epithelial and stromal compartments, respectively, in
      the doxazosin group, and 1.2% and 2.7% for the placebo arm. CONCLUSIONS: These
      data suggest apoptosis as the possible underlying molecular mechanism partly
      responsible for the clinical efficacy and morphological changes induced by
      doxazosin treatment in BPH.

PMID- 11341130
TI  - Lessons from cisapride.

PMID- 11341131
TI  - Child hunger in Canada.

PMID- 11341132
TI  - Child hunger in Canada.

PMID- 11341133
TI  - The environmental impact of war.

PMID- 11341134
TI  - Cisapride and patient information leaflets.

PMID- 11341135
TI  - Clinical examination for carpal tunnel syndrome.

PMID- 11341136
TI  - Clinical examination for carpal tunnel syndrome.

PMID- 11341137
TI  - Age-related differences in in-hospital mortality and the use of thrombolytic
      therapy for acute myocardial infarction.
AB  - BACKGROUND: Recent guidelines have acknowledged that thrombolysis decreases
      mortality from acute myocardial infarction (AMI) independently of age. The
      purpose of this study was to determine the age-related rates of thrombolytic
      administration and in-hospital mortality and the variables related to the use of
      thrombolytic therapy for patients with AMI. METHODS: A prospective cohort
      analysis involved a registry of 44 acute care Quebec hospitals that enrolled 3741
      patients with AMI between January 1995 and May 1996. The main outcomes of
      interest were crude and adjusted age-related in-hospital mortality rates and
      rates of use of thrombolytic therapy. RESULTS: In-hospital mortality rates
      increased dramatically with age from 2.1% in patients with AMI who were less than
      55 years of age to 26.3% in those who were 85 years of age or older. Overall,
      35.8% of the patients received thrombolysis. There was a pronounced inverse
      gradient in the use of thrombolysis with age, ranging from 46.2% in the youngest
      age group (< 55 years) to 9.5% in the oldest group (> or = 85 years). After
      adjustment for potential confounders, the older patients remained significantly
      less likely to receive thrombolytic therapy. Compared with patients who were less
      than 55 years of age, the odds ratio of receiving thrombolytic therapy was 0.68
      (95% confidence interval [CI] 0.52-0.89) for patients aged 65-74 years, 0.48 (95%
      CI 0.35-0.65) for patients aged 75-84 years and 0.13 (95% CI 0.06-0.26) for
      patients aged 85 years or more. Other variables related to thrombolytic therapy
      were diabetes (odds ratio [OR] 0.77, 95% CI 0.59-1.00), cerebrovascular disease
      (OR 0.46, 95% CI 0.30-0.72), angina (OR 0.73, 95% CI 0.56-0.95), typical chest
      pain (OR 2.56, 95% CI 1.88-3.47); ST elevation (OR 8.93, 95% CI 7.24-11.00), Q
      wave MI (OR 5.26, 95% CI 4.20-6.60) and increased length of time between onset of
      symptoms and arrival at hospital. INTERPRETATION: Age is an important independent
      predictor of in-hospital mortality and lower thrombolytic use following AMI.
      Other studies are required to further evaluate the appropriateness of
      thrombolytic therapy for elderly patients.

PMID- 11341138
TI  - Efficacy of a clinical medication review on the number of potentially
      inappropriate prescriptions prescribed for community-dwelling elderly people.
AB  - BACKGROUND: The administration of many drugs concurrently to elderly patients is
      a well-known problem in geriatrics and involves numerous risks. One way to reduce
      polypharmacy is to provide information to physicians in order to modify their
      prescribing practices. The main objective of this study was to evaluate the
      impact of an intervention program that targeted physicians with the aim of
      reducing the number of potentially inappropriate prescriptions (PIPs) given to
      elderly patients. METHODS: A randomized controlled trial was carried out among
      community-dwelling elderly people in Sherbrooke, Que. The participants were 266
      patients over 75 years of age (experimental group: n = 136, control group: n =
      130). A team comprising 2 physicians, a pharmacist and a nurse reviewed the list
      of drugs and the diagnoses of a subgroup of the experimental group in a case
      conference. Suggestions were formulated and mailed to the patients' physicians
      together with relevant scientific documentation justifying the recommendations.
      The main outcome measure was the number of PIPs. RESULTS: The mean number of PIPs
      per patient declined by 0.24 in the experimental group (n = 127) and by 0.15 in
      the control group (n = 116). The decline in PIPs was even larger in the
      experimental group that had case conferences (n = 80), in which the mean number
      of PIPs per patient declined by 0.31. However, this difference between the
      experimental group and the control group was not statistically significant in the
      intent-to-treat analysis. The number of drugs prescribed was not modified by the
      intervention, nor were the results of the global assessment of the patients' drug
      profiles. INTERPRETATION: This study suggests that the intervention program had
      no effect on the prescribing of PIPs.

PMID- 11341139
TI  - Schizophrenia: people's perceptions in Quebec.

PMID- 11341140
TI  - Thrombolytics in elderly patients: a triumph of hope over experience?

PMID- 11341141
TI  - New advances in the management of acute coronary syndromes.

PMID- 11341142
TI  - Continuing review of research approved by Canadian research ethics boards.

PMID- 11341143
TI  - New advances in the management of acute coronary syndromes: 1. Matching treatment
      to risk.

PMID- 11341144
TI  - PubMed: bridging the information gap.

PMID- 11341146
TI  - Drug patent protection: how long is long enough?

PMID- 11341145
TI  - Monitoring clinical research: report of one hospital's experience.
AB  - Monitoring of research by research ethics boards has been recommended by various
      organizations that fund clinical studies and by other groups. However, little
      evidence has been reported on the processes, costs and outcomes of these
      activities, information that would be helpful to guide the boards in their
      current work and future policies. We report here 3 years of monitoring experience
      by the research ethics board of a 313-bed university-affiliated community
      hospital. Activities newly implemented at the beginning of the study period
      included the use of recruitment logs, audits of completed consent forms and
      interviews with research subjects. Over the study period, we monitored 33
      protocols, through 188 consent form audits and interviews with 17 research
      subjects. In addition, 26 of 34 research investigators and collaborators
      responded to a survey about the monitoring. In general, the investigators were
      supportive of monitoring activities, but most were not willing to contribute
      financially. The types of monitoring we conducted are feasible and may be
      suitable (or could be adapted) for use in other institutions.

PMID- 11341147
TI  - Is Australia's safe injection site experiment bound for Vancouver?

PMID- 11341148
TI  - ORs closed after Aspergillus discovered at Royal Vic.

PMID- 11341149
TI  - Head-hunting in the health care jungle.

PMID- 11341150
TI  - Medical school enrolment growing too slowly?

PMID- 11341151
TI  - Down a dark (carpal) tunnel.

PMID- 11341152
TI  - One country, one medical licence!

PMID- 11341153
TI  - Canadians continue to spend more on drugs than doctors.

PMID- 11341154
TI  - Saskatchewan hopes to ease MD shortage by easing licensing requirements.

PMID- 11341155
TI  - Foot-and-mouth disease in animals and humans.

PMID- 11341156
TI  - Physicians and the pharmaceutical industry (update 2001).

PMID- 11341157
TI  - Mad cow's human toll.

PMID- 11341158
TI  - Taken to heart.

PMID- 11341159
TI  - Shape-shifters.

PMID- 11341160
TI  - Project skyhook.

PMID- 11341161
TI  - Antimicrobe marinade.

PMID- 11341162
TI  - A host with infectious ideas.

PMID- 11341163
TI  - Behind enemy lines.

PMID- 11341164
TI  - What's wrong with this picture?

PMID- 11341165
TI  - [Risk factors for early death and recurrence in stroke].
AB  - The early case fatality rate (28-day mortality) in 500 acute stroke patients of
      Budapest Stroke Data Bank was 17% and it was 25% within the first year with an
      increase between 1-3% annually. In the group with early death significantly
      higher age (p < 0.0001), more serious neurological symptoms, impaired
      consciousness (p < 0.0001), and higher volume of the lesions (p < 0.0001) have
      been detected. In this group significantly more stroke in the territory of
      vertebrobasilar system, a higher number of ischemic heart disease, and atrial
      fibrillation have been registered. According to the stroke subtypes there were
      significantly more cardiogenic embolisms, and hemorrhages, but less lacunar
      infarcts. The level of blood sugar at admission, and the rate of low platelets
      were higher among patients, who died within 28 days. Significantly higher
      percentage of the regions in the right frontal, right parietal, right occipital
      lobes and right thalamus have been affected in the early death group than in the
      survivors' group, however no such difference have been found in the lesions of
      the left homological structures. Severity of recurrent strokes have been more
      serious, and among patients with repetitive stroke significantly more ischemic
      heart diseases have been demonstrated. Atherosclerosis is the main risk for a new
      cerebrovascular accident. The case recurrent rate in the first 28 days is 7%, and
      it is 16% within the first year. The annual increase was between 1-5%. 71% of the
      recurrent strokes had the same mechanism as the first one.

PMID- 11341166
TI  - [Effectiveness of doxorubicin-docetaxel or doxorubicin-cyclophosphamide
      combination in advanced breast cancer with distant metastasis].
AB  - Between June 1996 and March 1998 a multinational multicentric phase III
      randomised comparative study was made for comparing 1. the effectiveness, 2. the
      adverse events and 3. the quality of life of two combinations i.e. DD versus DC.
      18 patients were treated with DD and 15 patients with DC. Age, tumour stage,
      visceral involvement, receptor status were well matched in the two groups. Good
      partial remission was obtained in 10 patients treated with DD whereas only seven
      remissions were seen in the DC arm. Response duration was similar in the 2 arms.
      No difference in adverse events was observed.

PMID- 11341167
TI  - [The role of uterine and umbilical artery Doppler velocimetry for the early
      detection of pathologic pregnancy].
AB  - Pregnancy induced hypertension remains the most frequent reason of maternal and
      fetal complications. Recent studies of the entire pathophysiology of the abnormal
      implantation proved association between the impaired placental performance and
      the reduced uteroplacental circulation. Therefore the Doppler examination of
      uterine and umbilical blood flow may provide the early recognition of high-risk
      pregnancies complicated by maternal hypertension and fetal intrauterine growth
      retardation. The authors endeavor to describe the details and characteristics of
      uteroplacental haemodynamic changes during the course of physiologic and
      defective implantation. On the basis of the currently available scientific
      publications they summarize the role of the uterine and umbilical artery Doppler
      velocimetry as a screening tool in the detection of the consequences of the
      impaired uteroplacental perfusion. They conclude that abnormal velocity waveforms
      obtained from the uterine and umbilical arteries may help to improve the efficacy
      of the prenatal care and the perinatal outcome as well. The clinical benefits of
      this screening method will be precisely defined on the basis of further
      multicenter studies in Hungary.

PMID- 11341168
TI  - [Granular cell tumor of the esophagus].
AB  - Granular cell tumor is a relatively rare, mostly benign lesion, that can be found
      in almost every organ, however, only 2% of the cases is oesophageal. It is named
      after the eosinophilic S-100 protein positive granula in the cytoplasm of the
      tumor cells. Since patients with oesophageal granular cell tumor are mostly
      symptomless, the tumor is usually found accidentally. Even in patients with
      dysphagia, contrast radiograph and gastroscopy show an atypical picture,
      therefore, the diagnosis is based on the histological examination. Therapy is
      usually conservative, but surgical treatment might be necessary sometimes. A
      patient with severe dysphagia is reported here. She was diagnosed with a granular
      cell tumor in the oesophagus, and the tumor was surgically removed.

PMID- 11341169
TI  - [Representation of obstetrics on Hungarian medical coins].

PMID- 11341170
TI  - [Remembering Dr. Adolf Onodi, professor of rhinolaryngology, member of the
      Hungarian Academy of Sciences].

PMID- 11341171
TI  - [Gastric atony. Classical article. 1901].

PMID- 11341172
TI  - Possible mechanisms of diabetic fetopathy.
AB  - By using immunoaffine chromatography and ELISA it was found that 30-35%
      polyclonal of anti-insulin antibodies (AB1) in sera of diabetes patients has
      bound with high-affinity to Nerve Growth Factor (NGF). This indicates the
      presence of common epitop(s) in both molecules and could be a reason for NGF
      deprivation during formation of the nervous system in fetuses of diabetic
      pregnant women. Patient sera also usually characterized by elevated level of
      antiidiotypic antibodies (AIAb2) which interact with membrane insulin receptors,
      and may induce the general metabolic disturbances in fetus and newborns from
      diabetic mothers, fatal sometimes. High levels of anti-insulin/NGF Ab1 may bind
      excess of AIAb2 and prevents the insulin receptors dysfunction (typical for
      newborns in satisfactory health state). On the other hand--children with elevated
      levels of Ab1 at age 1-3 years often revealed clinical signs of neuropathology.

PMID- 11341173
TI  - Analyzing the peripheral blood antibody repertoire of a celiac disease patient
      using phage antibody libraries.
AB  - Celiac disease (CD) is an autoimmune enteropathy characterized by intestinal
      malabsorption and immunological responses to dietary gliadins and an auto antigen
      located in the endomysium. The latter has recently been identified as the enzyme
      tissue transglutaminase (tTG). The linkage between gliadins, tTG and the
      autoimmune response has still to be clarified. In this work we report the
      production and analysis of a phage antibody library from the peripheral blood
      lymphocytes (PLB) of a CD patient. The library contained polyreactive and
      monoreactive antibodies to alpha-gliadin, to the dietary antigen beta
      lactoglobulin, but not to tTG. The majority of the VH regions of the anti-alpha
      gliadin antibodies belonged to the VH 4 family. The possibility of exploiting
      phage display antibodies as tools to study the molecular events associated with
      CD is discussed.

PMID- 11341174
TI  - Selection and characterization of single chain Fv fragments against murine
      recombinant prion protein from a synthetic human antibody phage display library.
AB  - We describe the selection of single chain Fv fragments (scFv) against recombinant
      murine prion protein (mPrP) from a synthetic human antibody phage display
      library. Six different antibodies were isolated after three rounds of panning
      against full-length mPrP. All antibodies recognized a truncated form of mPrP
      containing residues (121-231). The amino acid sequence of the CDR3 of the scFv
      fragments has been determined. Five of the antibodies have been over-expressed,
      purified and their affinity for full-length mPrP determined by ELISA. The
      observed binding affinities vary from 30 nM to 2.7 microM.

PMID- 11341175
TI  - Changes of maternal serum natural antibodies of IgG class to proteins MBP, S100,
      ACBP14/18 and MP65 and embryonic misdevelopments in humans.
AB  - Immunoreactivity that is contents/affinity of natural antibodies (N-Ab) of IgG
      class to developmentally related proteins MBP, S100, ACBP14/18 and MP65 were
      measured in serum samples of 1987 women at their pregnancy terms of 3-12 weeks.
      The pregnancy results of the examined women were analyzed 4-9 months later. It
      was revealed that frequencies of cases of stopped early pregnancies, intrauterine
      and antenatal fetal deaths, and births of newborns with coarse inborn defects are
      directly related to deviation of the examined maternal N-Ab content/affinity from
      the physiological limits: abnormally high as well as abnormally low reactivity
      during first trimester of pregnancy, both could be related to unfavorable results
      of pregnancy.

PMID- 11341176
TI  - Monoclonal antibody CIBCHTB1 defining an epitope on carcinoembryonic antigen
      (CEA).
AB  - Carcinoembryonic antigen (CEA) is an oncofoetal protein first identified by Gold
      and Freedman (1965) in colorectal cancer. It is a cell surface tumor marker which
      has been characterised as a heterogenous group of glycoproteins. It is also
      present in a variety of benign and non-neoplastic diseases like ulcerative
      colitis, Adenomatous polyp, Liver cirrhosis and other cancers like GI tract
      tumors, Cancer of the breast, lung, ovary, pancreas, prostate, hepatoma etc.
      Elevated CEA levels serve as clinical tool in the diagnosis, monitoring,
      detecting early any recurrence or metastasis and in prognostication for confirmed
      colorectal cancers. In order to develop an Enzyme Immuno Assay and
      immunocytochemical assay for CEA, an MAb designated as CIBCHTB1 has been
      generated using CEA isolated from a cell line HT115, human adenocarcinoma of the
      colon, as immunogen by the conventional Hybridoma technology. This MAb of IgG1
      isotope was selected by screening of culture supernatents by ELISA and then by
      its high binding affinity with HT115 cells as revealed by flowcytometric
      analysis. By ABC method of immunocytochemical assay, this Ab exhibited strong
      staining of cells in frozen tissue sections of normal colon and malignant
      colorectal lesions and various other types of human cancers. This MAb has useful
      application to study the expression of CEA in human cancers. Serum CEA levels of
      patients with colorectal cancers and other CEA producing cancers and controls
      determined by EIA using this MAb were in good correlation with the results
      obtained using commercial kit. The diagnostic potential of this Mab in the
      management of colorectal cancers is discussed.

PMID- 11341177
TI  - Antibodies to hepatitis B virus and hepatitis C virus in residential
      detoxification clients in Jamaica.
AB  - The role of non-injecting drug abuse in viral hepatitis has not been studied
      widely and is not well understood. A total of 301 substance abusers, residents of
      a detoxification/rehabilitation unit, were investigated for exposure to hepatitis
      B virus (HBV) and hepatitis C virus (HCV). Samples of serum were tested for anti
      HCV and anti-HBc antibodies and HBsAg. All of the patients were non-injecting
      drug users (non-IDUs). The prevalence of anti-HCV was 1.7%; anti-HBc was found in
      28.7% and HbsAg in 0.6% of patients. Anti-HCV positivity correlated with the
      presence of elevated aminotransferases (80%). Exposure to HBV correlated
      significantly with gender (p < 0.05); age (p < 0.05); and duration of substance
      abuse (p < 0.05). No significant correlations were found between HCV and/or HBV
      infection, the drug of abuse, HIV, HTLV-1 or syphilitic infection. Residential
      detoxification/rehabilitation provides an opportune moment to identify and treat
      HCV positive substance abusers in the attempt to avert the severe hepatic
      sequelae. Measures which exclude substance abusers from volunteer blood donation
      should be considered.

PMID- 11341178
TI  - Sleeping like a baby: attitudes and experiences of bedsharing in northeast
      England.
AB  - This paper reports findings from a study that investigated infant care practices
      in a small population of Northeast England in order to determine whether parent
      infant bedsharing is common parenting behavior. In a year-long prospective study
      we examined the opinions and practices of parents with regard to their infants'
      nighttime sleeping strategies before and after the birth of their babies. Results
      confirm that parents pursue a heterogeneous array of nighttime parenting
      strategies and that 65 percent of the sample had actually bedshared. Parents with
      no previous intention to do so slept with their babies for a variety of reasons.
      One of this study's most important findings is that babies were being brought
      into bed with both parents. Ninety five percent of the bedsharing infants slept
      with both mother and father. This study has shown that bedsharing is a relatively
      common parenting practice. Despite initial worries and fears, mainly concerning
      overlaying, some parents found bedsharing an effective option yet were covert in
      their practices, fearing the disapproval of health professionals and relatives.

PMID- 11341179
TI  - Power in the nursing home: the case of a special care unit.
AB  - This article examines the effects and nature of power in a special care unit of a
      nursing home devoted to elders with dementia and/or disturbed behaviors. Drawing
      from two case studies and contemporary theories on power, I illustrate how the
      hierarchical structure of the clinic, together with the diffuseness and
      pervasiveness of disciplinary power, serves to shape the lives of--and to
      constrain the resistance opportunities open to--elders within the clinic. I also
      discuss the dilemma facing ethnographers of the clinic who may witness the
      sometimes disastrous effects of power but feel incapable, in their positions as
      researchers, of challenging the actions of clinical staff. At the same time, I
      observe how the contradictions of disciplinary power are often experienced by
      clinical staff who themselves struggle between taking actions they feel they must
      and those they would prefer. Far from acceding to the impotency that clinical
      anthropologists too often feel within a research setting, I argue that they can
      help to incite in their clinical colleagues the urgency of carrying out more
      productive alternatives to conventional "disciplinary" practices.

PMID- 11341180
TI  - From quarantine to condoms: shifting policies and problems of HIV control in
      Cuba.
AB  - This study reviews HIV prevention in Cuba in light of (1) the liberalization of
      HIV quarantine, (2) the growth in tourism, and (3) the aggressive system of
      public health promotion. Sixty-two key informants, including Cubans who are HIV
      positive, at risk, or working as health professionals, were interviewed during
      June and July of 1996. Findings include: (1) there is a common public perception
      that the government's national HIV screening and contact tracing system obviates
      the need for individual precaution; and (2) both commercial sex workers and men
      who have sex with men believe that legal and social forces hinder their
      indigenous HIV prevention efforts. A well developed system of preventive health
      care offers the potential for effective HIV prevention. The fact that Cuban
      officials use the success of their HIV/AIDS control program to promote national
      pride may retard appropriate changes in their response to currently rising levels
      of infection.

PMID- 11341181
TI  - [Histoacryl vs Dermabond cyanoacrylate glue for closing small operative wounds].
AB  - Acrylate glues used in a childrens' day care unit to close small surgical wounds
      were compared. In 157 children, aged 12 weeks to 3.7 years, either Histoacryl or
      Dermabond was used (respectively, H: Ethicon Inc., Johnson & Johnson, NJ or D:
      Dermabond, Braun Surgical Gmbh, Melsungen, Germany). Operations were for inguinal
      hernia (110 cases), hydrocele (25), undescended testis (16), umbilical hernia
      (13) and funiculocele (3). 1 week after surgery the wounds were evaluated in
      terms of integrity of closure, redness or infection, need for antibiotics, wound
      granuloma, and parental satisfaction with instructions and actual method of wound
      caring. 3 months after surgery the wound/scar was reexamined. The margins of the
      wounds were separated partially or completely in 8 of 85 in group H (9.4%) while
      in the D group, 2 wounds (2.4%) had partially opened (p < 0.05). There were no
      differences between the glues with regard to wound infection or cosmetic results.
      Parental satisfaction was higher with D (96%) than H (82%) but the difference was
      not statistically significant. It is convenient to use glue to close operative
      wounds in children after ambulatory surgery. The use of D significantly reduced
      wound ruptures compared to H. Long-term cosmetic results were similar.

PMID- 11341182
TI  - [Pneumomediastinum following drug abuse].
AB  - Pneumomediastinum is termed spontaneous when not associated with trauma or other
      identifiable pathological process. There are several reports of pneumomediastinum
      following narcotic drug inhalation or smoking while applying positive pressure.
      We describe a 37-year-old male drug addict, hospitalized after having being found
      unconscious with shortness of breath. CT scan demonstrated bilateral pneumonia
      with pneumomediastinum. After a day of mechanical ventilation he gradually
      recovered and the mediastinal air disappeared. Pneumomediastinum may occur in
      addicts but usually has no dangerous clinical consequences. If there is
      respiratory deterioration another cause should be sought.

PMID- 11341183
TI  - [Atrophic gastritis presenting with pulmonary embolism].
AB  - Atrophic gastritis is an autoimmune gastropathy in which there is destruction of
      gastric parietal cells. This results in intrinsic factor deficiency and
      disturbance in vitamin B12 absorption. Its clinical manifestationa are therefore
      the consequences of B12 deficiency and include anemia and neurological defect. In
      addition, lack of B12 results in metabolic changes, including disturbances of
      methionine metabolism and accumulation of homocysteine. In recent years, there
      has been increasing evidence suggesting that hyperhomocysteinemia is a risk
      factor for thrombo-embolic disease. We describe a 51-year-old man with atrophic
      gastritis, severe B12 deficiency and hyperhomocysteinemia. The initial clinical
      manifestation was pulmonary embolism, without either anemia or neurological
      signs. B12 deficiency should therefore be considered in patients being
      investigated for hypercoagulability.

PMID- 11341184
TI  - [Folic acid use by pregnant women in Israel for preventing neural tube defects].
AB  - Spina bifida and anencephaly are the most common, serious malformations in neural
      tube defects (NTD). Randomized trials in the last 2 decades have demonstrated
      that folic acid, 0.4 mg/d, reduces the incidence of NTD by more than 50%. We
      investigated the use of folic acid and multivitamins containing folic acid in
      childbearing women. Of 221 women interviewed, 67 (30%) regularly took pills
      containing 0.4 mg folic acid. Women with higher educational levels were more
      likely to take multivitamins with folic acid than were the less educated (p =
      0.05). Of the women who took folic acid, only 5 (7.5%) used separate folic acid
      tablets, before and during their pregnancy. The rest used multivitamins
      containing folic acid. The 5 women who took folic acid separately were college
      educated and nonreligious, and they took multivitamins in addition (p > 0.05). Of
      the women interviewed, 58 (26.2%) were Bedouin of the Negev. 24 (41.4%) of them
      took pills containing folic acid on a regular basis. This percentage is higher
      than that in the Jewish women in the study who took folic acid for prevention of
      NTD (17%; p = 0.038). Most of the women took folic acid after the first
      trimester. Only a minority took daily periconceptional folic acid. Multivitamins
      containing 0.4 mg of folic acid were more popular than folic acid tablets alone.
      This study emphasizes the need for continuing efforts to increase consumption of
      folic acid and awareness of its benefits among women of childbearing age.

PMID- 11341185
TI  - [Assisted reproductive technologies reported in the National Registry of Israel
      1995-1996].
AB  - National registration of the results of assisted reproductive technology (ART) is
      maintained by many countries. The Israel Committee for Registry of ART asked 19
      in-vitro fertilization (IVF) units in 1995 and 20 in 1996 to report on their
      activities and results. Data were collected by questionnaires and analyzed by
      computer. The most common ovarian stimulation was the combination of GnRH agonist
      and gonadotropins. There were 10.89 treatment cycles in 1995, of which 45% were
      with intracytoplasmic sperm injection (ICSI). In 1996, of 12.72 cycles, 54% were
      with the ICSI procedure. Embryos were transferred into the uterine cavity in 90%
      of the conventional IVF cycles and in 95% of the ICSI cycles. The overall
      pregnancy rate was 22% per embryo transfer in the conventional IVF and ICSI
      cycles. The delivery rate was 13.7% and 15.4% per embryo transfer in the
      conventional IVF and ICSI cycles, respectively. The rates for abortion and tubal
      pregnancy were 24% and 1.3%, respectively. These results are better than in
      previous years and are comparable with results in some western European
      countries. Efforts are being made to convert the registry into a real-time
      computerized system.

PMID- 11341186
TI  - [Prematurity as an interplay between psychological and biological risk factors
      leading to infant psychopathology].
AB  - Concepts such as risk factor, vulnerability, protective factor and resiliency
      have become central in the field of developmental psychopathology. The birth of a
      very-low-birth weight premature baby can be used as a paradigm of the interplay
      between these factors. Indeed, prematurity implies for both infant and parents,
      biological as well as psychological risk factors. They may interact in such a way
      that the child's emotional, cognitive and social development will deviate from
      normal. Understanding the psychological impact of premature birth includes
      reference to both the normal psychological processes that characterize pregnancy
      that are jeopardized by a premature, often traumatic delivery, and to the special
      significance of being a parent in the Special Care Nursery. The contrast between
      the expected appearance of the baby and that of the sick-looking, tiny premature,
      together with uncertainty about its medical status, often affect the parents'
      bonding process. In addition, parents must learn quickly to cope with issues such
      as total dependence on a very busy team, loss of control of the care of their
      baby, and their unclear roles as parents. Added to these risk factors are the
      specific neurobehavioral characteristics of premature babies, which often make it
      hard for parents to read their cues and respond to them properly. A clinical
      vignette illustrates the chain of psychological and biological events that lead
      to severe disturbance of the early parent-child relationship. It also brings up
      the question of psychosocial intervention in the Special Care Nursery, both in
      terms of early detection of families at risk and the types of intervention.

PMID- 11341187
TI  - [A molecular method of diagnosis of congenital adrenal hyperplasia].
AB  - Congenital adrenal hyperplasia (CAH) is caused mainly by deficiency of the 21
      hydroxylase enzyme. The disease may appear in the classical salt-losing, simple
      virilizing forms or as a mild, nonclassical form. 21-hydroxylase is encoded by
      the CYP21B gene on the short arm of chromosome 6, in the midst of the human
      leukocyte antigen (HLA) complex, between HLA Class I and Class II regions. We
      describe a method for identifying mutations in the CYP21B gene. It is based on
      amplification of the gene using the polymerase chain reaction and identification
      of mutations with sequence-specific oligo-probes. The mutations identified were:
      V281 and P30L responsible for nonclassical CAH, and 12 splice, Q318X, I172N,
      cluster E6, and a deletion including 8bP in the third exon (8bP del) responsible
      for the classical form of CAH. We also analyzed 2 families affected with the
      classical form of CAH which demonstrate possible complications in genotyping.
      Typing for HLA haplotypes can be helpful in certain cases, as demonstrated in 1
      of the families presented. In this case it was necessary to distinguish between 2
      possible genotypes: 1 with the mutations in tandem on 1 chromosome and the other
      with the mutated genes on both chromosomes. HLA haplotyping enabled the
      assignment of the mutations to the relevant chromosomes and thus allowed correct
      genetic counseling. The other family demonstrated the importance of CYP21B
      genotyping in individuals with the nonclassical form of CAH. This form may
      consist of 1 mild and 1 severe mutation, representing a serious potential for
      transmitting the classical form of CAH.

PMID- 11341188
TI  - [Surgery for blepharoptosis in muscular dystrophy].
AB  - In some muscular dystrophies there is ocular involvement characterized by
      blepharoptosis and ophthalmoplegia. These conditions occur in chronic progressive
      external ophthalmoplegia, oculopharyngeal muscular dystrophy, mitochondrial
      myopathy, myotonic dystrophy, and ocular myasthenia, among others. Although they
      differ in their systemic clinical manifestations and in genetic inheritance,
      ocular involvement is common to all of them. Manifestations include bilateral
      progressive blepharoptosis with or without extraocular muscle malfunction. During
      surgical repair of the ptotic eyelid, consideration must be given to eyeball
      movements, in addition to maximal eyelid elevation, and to avoiding
      overcorrection and consequent corneal overexposure, leading to dryness and visual
      impairment. With these muscular dystrophic disorders, resection of the levator
      muscle or blepharoplasty alone does not suffice. Follow-up shows that most
      patients need a secondary repair after a short while. Operative correction uses a
      frontalis sling for eyelid elevation and support. A series of 8 patients with
      these diseases, operated on by various surgical techniques during the past 7
      years, is presented.

PMID- 11341189
TI  - [Eosinophilic pneumonia induced by minocycline].
AB  - Eosinophilic pneumonia is a rare adverse effect of minocycline. To date there are
      about 70 chemical compounds that cause drug-induced, eosinophilic lung disease. A
      20-year-old woman who developed eosinophilic pneumonia due to minocycline is
      described. Diagnosis was established by history, signs and symptoms, peripheral
      eosinophilia, chest x-rays and response to combined cessation of treatment and a
      short course of steroids. Physicians should be aware to this rare adverse effect
      of the drug. Attention to the possibility of minocycline-induced eosinophilic
      pneumonia can prevent unnecessary, expensive investigation. Cessation of intake
      is usually sufficient for cure.

PMID- 11341190
TI  - [Are research physicians an endangered species in Irael?].

PMID- 11341191
TI  - [Tissue transglutaminase--the main enzyme in pathogenesis and diagnosis of celiac
      disease (ileus)].

PMID- 11341192
TI  - [Metalloproteinases and their inhibitors: the importance of extracellular matrix
      degradation in malignancy].

PMID- 11341193
TI  - [Doctor, what should I do about the tissue covering my eye? Pterygium:
      epidemiology, natural history and current treatment].

PMID- 11341194
TI  - [Immune recovery in AIDS patients: changes in the clinical presentation and
      therapy of cytomegalovirus retinitis].

PMID- 11341195
TI  - [New understanding in the prevention of post-coronary angioplasty restenosis].

PMID- 11341196
TI  - [Genetic contribution to the etiology of anorexia nervosa].

PMID- 11341197
TI  - [Treatment of the overactive bladder with detrusitol].

PMID- 11341198
TI  - [Dry mouth: a common adverse effect of medication].

PMID- 11341199
TI  - [Medical selection of free immigration to Israel--the debate on the medical
      limits during the large immigration in the Fifties].

PMID- 11341200
TI  - [Medical use of animals and animal matter in Israel and its neighboring countries
      during Middle Ages].

PMID- 11341202
TI  - [First Israeli Conference on Aerosols in Medicine, Tel Aviv, 29.6.2000].

PMID- 11341201
TI  - [Jonas Edward Salk (1914-1995)].

PMID- 11341203
TI  - [Problems in fetal monitoring characteristic of risks for malpractice suits].
AB  - Medical malpractice suits in obstetrics comprise about 10% of all claims against
      medical institutions in Israel. A significant proportion are due to failures
      relating to fetal monitoring. We studied the characteristics of 102 of 4125
      obstetrical cases reported to the Medical Risk Management Co. as being at risk
      for a malpractice suit. The cases were divided into those with medical management
      failures (misinterpretation of fetal monitor tracing, failure to respond promptly
      to fetal monitoring indicating distress, etc.) and technical failures (loss of
      monitor tracings, interruption in the tracing at a critical time, unreadable
      tracings, etc.). The monetary quantum in fetal monitoring failures exceeded
      $30,000,000. The majority of these failures could have been avoided by using
      central electronic fetal monitoring systems with alerting and archival
      capabilities.

PMID- 11341204
TI  - [Postmortem sperm procurement--juridical and Halachic aspects].
AB  - The ability to fertilize human ova with sperm retrieved soon after death has been
      utilized in Israel and in other countries. However, postmortem sperm procurement
      (PMSP) has significant Halachic, juridical and ethical implications with regard
      to both the action of sperm and its implications for mother and offspring. In
      specific situations, and with reliable supervision aimed at preventing sperm
      interchange, Halacha may allow the procedure, while the juridical approach in
      such a situation is not as yet well established. As for Halacha, even if a son is
      born, the widowed mother will still be obligated by the Halacha of yibum
      (marrying the deceased husband's brother). The child's rights as heir, aspects of
      implications for its future life, or even social aspects of PMSP, all are factors
      to be seriously considered before PMSP is performed, without bias by temporary
      emotions. Thus, PMSP should be reserved for only very special circumstances, and
      only after consultation with the appropriate medical, Halachic, juridical and
      ethical experts.

PMID- 11341205
TI  - [Laparoscopic cholecystectomy--1,000 procedures in a surgical department].
AB  - The first 1,000 laparoscopic cholecystectomies performed in our department were
      reviewed. There was no operative mortality; conversion to open cholecystectomy
      was necessary in 2%. In the last 600 cases the rate of conversion had decreased
      to 0.5%. There was common bile duct injury in 0.3%, with the injuries identified
      during primary surgery. This clinical experience is consistent with previous
      studies, which proved that laparoscopic cholecystectomy is safe and should
      replace open operation as the procedure of choice.

PMID- 11341206
TI  - [Regulation of natural medicines in Israel and abroad].
AB  - Hand-in-hand with the public's growing interest in health care, there has been an
      increasing demand for natural health products considered both safe and medically
      effective. But many such products have not been shown to meet efficacy and safety
      criteria and therefore can not be registered as pharmaceuticals. On the other
      hand, it is quite clear that some products do have pharmacological activity and
      are being used for therapeutic or preventive effects. In Israel, the marketing
      rules for food or dietary supplements prevent their manufacturers from claiming
      medicinal/healing properties that the product might have, and allow only limited
      health statements. But great demand for these products has created massive
      publication attributing medicinal indications for products whose quality,
      efficacy and safety have neither been examined nor proven according to accepted
      medical criteria. We review the regulation and supervision of natural health
      products in Israel and other developed countries and find a broad range of
      opinions about natural health products. They range from acceptance as
      conventional drugs reimbursable by health insurance, as in Switzerland and
      Germany, to their status as dietary supplements requiring no significant
      authorization or supervision, as in the USA. Analysis of the current situation in
      Israel and the western world would indicate that some natural health products do
      possess pharmacological activity and therefore manufacturers should be allowed to
      make limited claims for specified therapeutic properties. A stricter set of
      registration regulations are needed for proof of safety, efficacy and quality of
      these products, but more lenient than those for registering a pharmaceutical
      product.

PMID- 11341207
TI  - [Coloring the floor of Schlemm's canal in deep sclerectomy].
AB  - Increased intraocular pressure in glaucoma, resistant to maximal tolerated
      medical therapy, can be relieved by deep sclerectomy. Its advantage over
      classical trabeculotomy is fewer postoperative complications. This probably
      results from its being relatively noninvasive, since the anterior chamber is not
      penetrated. Successful deep sclerectomy requires preservation of the trabeculo
      descemetic membrane, which forms part of the floor of Schlemm's canal. Aqueous
      flows from the anterior chamber across the trabeculo-descemetic membrane and into
      the ocular venous drainage. Despite the importance of its preservation, during
      deep sclerectomy it is perforated in 10-15% of cases. Coloring the endothelium
      lining the floor of the canal with gentian violet solution improves visualization
      of the membrane and thus aids in its preservation. Its use makes the procedure
      easier and should improve results.

PMID- 11341208
TI  - [The Zavanelli maneuver--back to the womb].
AB  - The Zavanelli maneuver is the manual replacement of a partially-born fetus due to
      severe shoulder dystocia. It is described in obstetrical textbooks as being among
      the last to be tried in a series of maneuvers to rescue the fetus with severe
      shoulder dystocia, as it is considered a very difficult and heroic maneuver. Few
      obstetricians have seen it and fewer have done it themselves. It is even more
      rare when a single obstetrician has done the Zavanelli maneuver repeatedly.
      Therefore, both experienced obstetricians and certainly young residents are
      fearful when they have to use this maneuver and can lose control in cases of
      shoulder dystocia. We have found descriptions of 93 cases of use of the Zavanelli
      maneuver in vertex presentations. We also describe a recent case in our
      experience. We conclude that this maneuver is safe and not too difficult to
      perform even without previous experience. Fetal and maternal complications are
      few, but there is of course a bias against reporting bad results. We recommend
      that every obstetrician become familiar with this maneuver so as to feel sure
      that it is safe for him to use in severe cases of shoulder dystocia.

PMID- 11341209
TI  - [Burch laparoscopic procedure for repairing proven stress incontinence--report of
      32 cases].
AB  - There are more than 200 procedures for repairing stress urinary incontinence. We
      evaluated the safety and efficiency of the Burch laparoscopic procedure in 32
      women with urodynamically proven genuine stress incontinence. Mean operating time
      was 40 minutes and mean hospitalization time after the procedure was 30 hours.
      The cure rate was 97%, similar to that reported in other studies (80-95%). The
      major complications were 2 cases (6.2%) of unintended bladder injury, diagnosed
      and repaired laparoscopically. Although follow-up has only been for 3-42 months,
      the high cure rate and safety and advantages of laparoscopy over laparotomy, make
      laparoscopic Burch colposuspension the procedure of choice for repairing stress
      incontinence.

PMID- 11341210
TI  - [Penile reconstruction after complete glans amputation during ritual
      circumcision].
AB  - Circumcision, so commonly performed, is considered a safe procedure rarely
      associated with significant complications. A case of complete amputation of the
      glans penis during neonatal circumcision is reported. The glans was successfully
      reimplanted, with good post-operative functional and esthetic results.

PMID- 11341211
TI  - [Pulmonary adenocarcinoma in myasthenia gravis--autoimmunity and late development
      of malignancy].
AB  - We report a 75-year-old man with myasthenia gravis for many years, who was
      hospitalized because of cough, fever, and dyspnea. Chest x-ray revealed a
      bilateral pleural effusion. Adenocarcinomatous cells were found in the pleural
      fluid. Computerized tomography of the chest showed widespread pulmonary
      dissemination of the tumor. The relationship between myasthenia gravis, an
      autoimmune disease involving the motor end-plate, and malignancy (thymoma) has
      been widely recognized. Current literature documents few reports of lung
      malignancies with concurrent development of myasthenia gravis. A tentative
      explanation, based on current research, is provided for the possible role of
      myasthenia gravis and the late development of lung cancer. Moreover, a model for
      the autoimmune phenomenon and the development of late malignancies is provided
      with explicit explanations. It is important to search for occult, developing
      malignancies in newly diagnosed autoimmune diseases.

PMID- 11341212
TI  - [Oral rehydration in acute gastroenteritis in infants and children--advantages of
      a standardized protocol].
AB  - Oral rehydration (OR) for acute gastroenteritis in infants and children has been
      shown to be as effective as IV therapy, with less discomfort and lower costs. In
      this retrospective study we compared 2 pediatric wards, in 1 of which only a
      standardized, simplified, bedside protocol, based on American Academy of
      Pediatrics guidelines, was used. There were no significant clinical
      characteristics in the 208 patients. In the ward which used the above protocol,
      OR utilization was significantly more frequent than in the other ward (48% versus
      15%), thus saving equipment costs of nearly $1,000/3 months. There were no
      significant differences in outcome between the wards. We conclude that
      introducing a standardized management protocol may increase OR utilization in
      hospitalized children with acute diarrhea.

PMID- 11341213
TI  - [Changing of the guard--tribute to Ya'acov Rotem].

PMID- 11341214
TI  - [Cellular phones--prosperity or carcinogenesis].

PMID- 11341215
TI  - [Will cystatin C replace creatinine as the endogenous metabolite for measuring
      GFR?].

PMID- 11341216
TI  - [Periarticular new bone formation following traumatic brain injury].

PMID- 11341217
TI  - [Monteggia fractures in children and adults--an update].

PMID- 11341218
TI  - [Elective cesarean section for every pregnant HIV carrier--is it justified?].

PMID- 11341219
TI  - [Criteria for safe discharge after ambulatory surgery].

PMID- 11341220
TI  - [Integration of erythropoietin in radiotherapy for malignant diseases].

PMID- 11341221
TI  - [Hereditary basis of attention deficit and hyperactivity disorder].

PMID- 11341222
TI  - [Non-cardiogenic pulmonary edema following upper airway obstruction in adults].

PMID- 11341223
TI  - [Treatment of calf vein thrombosis--has the debate ended?].

PMID- 11341224
TI  - [Increased physiological vulnerability of women to alcohol and its significance
      in preventive medicine].

PMID- 11341225
TI  - [Attitudes of physicians and the medical system in Israel to the Holocaust].

PMID- 11341226
TI  - [A hospital in the Land of Israel 110 years ago--Baron Rothschild's hospital in
      Rishon Letzion (1891-1901)].

PMID- 11341227
TI  - Recommendations for the reporting of surgical specimens containing uterine
      cervical neoplasms.

PMID- 11341228
TI  - [The concept of quality of life in a group of nursing teachers--elements for
      reflection].
AB  - It is a qualitative study, which was realized from the concept of quality of
      life, adopted by Meeberg (1993) and it is related to the opinion of a group of
      nursing teachers. It was observed that this concept is current in the speech of
      the people who were interviewed in a very clear way, especially in the attributes
      which are related to life itself and to an acceptable physical, mental, social
      and emotional state.

PMID- 11341229
TI  - [The effect of anxiety on the patient's cognition in the postoperative period].
AB  - The man confronting surgery and anesthesia, has hormonal alterations provoked by
      the anxiety, modulated by the cognitive evaluation done in the person that faces
      this situation and were accompanied by perceptible physiologic alterations. The
      goals of this study were to verify the influence of trate-anxiety and state
      anxiety in psychobiological manifestation of patient in immediate post-operative
      period. The data were collected using trate and state anxiety inventary, two
      questionnaires to evaluate clinical conditions of 33 surgical patients. The data
      were collected in immediate pre-operative and post-operative periods. The results
      showed a significative correlation between trate and state anxiety in pre
      operative period. There was no significative correlation among state anxiety in
      pre-operative period and clinical conditions in post-operative period. As
      conclusion, the correlation was no significative among trate anxiety, state
      anxiety and psychobiological manifestations in post-operative period.

PMID- 11341230
TI  - [Family planning in Brazil in the context of public health policies: important
      historical factors].
AB  - This study searches historical records for the formulation and implementation of
      public health policies in Brazil, focusing on those referent to family planning.
      Initial conclusions show that the policies were geared toward international
      controlling interests. Family planning today, though officially recognized as an
      inalienable right of every citizen, still reflects the contradictory political,
      economic and ideological interests of the ruling power.

PMID- 11341231
TI  - [Is blood pressure being measured?].
AB  - The blood pressure measure is part of the physical exam and it should be
      accomplished in every medical consultation. To verify the blood pressure measured
      in the accomplished medical consultations record of first they were consulted it
      consults 500 patient's ambulatorial being 335 (67%) coming of medical and
      surgical clinics and 165 (33%) of the gynecological and obstetric clinics. The
      blood pressure was written down in 39% of the accomplished consultations (135 +
      32 mm Hg 85 + 19 mm Hg), and 11% of this annotations the pressure diastolica was
      above 90 mm Hg. In relation to the previous diagnosis of hypertension it was
      verified that: a) in 62% of the records there was not this information; b) 20%
      referred to have hypertension, and in 79% of these the arterial pressure was
      scored; and c) 18% referred not to have hypertension and 46% of these had
      registration of the arterial pressure. Therefore, most of the patients didn't
      have its logged arterial pressure.

PMID- 11341232
TI  - [Family planning policies in Joao Pessoa-PB: analysis of the contradictions
      between official and practical discourses].
AB  - This research project's main objective is to analyze the contradictions
      encountered between official and practical discourses referent to family planning
      in public health policies in Joao Pessoa, PB, Brasil, using as its reference,
      PAISM (Program for Assistance in Women's Health). The policy was analyzed
      according to its official intentions and its practical use through interviews
      with people linked to PAISM. It was concluded that, this program is being
      developed under a utilitarian ideal, negating the individual citizen's right to
      regulate one's own fertility.

PMID- 11341233
TI  - A case of adenoid squamous cell carcinoma of the breast skin.

PMID- 11341234
TI  - Reply to: Lipoprotein (a) and chronic obstructive pulmonary disease.

PMID- 11341235
TI  - Obituary: Bjorn Ekwall, MD, Associate Professor of Toxicology.

PMID- 11341236
TI  - Oxygen radical-mediated reduction in basal and agonist-evoked NO release in
      isolated rat heart.
AB  - Oxygen free radicals (OFR) play a primary role in ischemia-reperfusion-mediated
      vascular dysfunction and this is paralleled by a loss of endothelial nitric oxide
      synthase (eNOS) activity. The authors tested whether a direct exposure to OFR may
      affect vascular relaxation by altering nitric oxide (NO) release. Effects of
      electrolysis(EL)-generated OFR on basal and agonist-evoked NO release were
      monitored in isolated rat hearts by oxyhemoglobin assay. Electrolysis-induced
      changes were compared with those obtained after 30 min perfusion with NOS and
      cyclooxygenase (COX) inhibitors NG-nitro-L-arginine methyl ester (L-NAME, 100
      microM) and indomethacin (INDO, 1 m M). Electrolysis-generated hydroxyl radical
      (.OH) formed by.O2-and H2O2 via the Fenton reaction as revealed by Electron
      Paramagnetic Resonance (EPR). After EL, basal NO release declined by 60% and
      coronary perfusion pressure (CPP) increased by approximately 70%. L-NAME/INDO
      perfusion similarly lowered NO release (-63%) but increased CPP less than EL
      (56+/-3%P<0.03 v post-EL). In presence of excess substrates and cofactors eNOS
      activity was not affected by EL. Both acetylcholine (ACh; 1 microM) and
      bradykinin (BK; 10 n M) had minimal effect in reversing EL-induced
      vasoconstriction, whereas both partially reversed L -NAME/INDO-mediated
      constriction. Sodium nitroprusside (SNP, 1 microM) completely reversed L
      NAME/INDO constriction and partly countered that after EL (-38+/-2.5, P<0.001).
      Acetylcholine-evoked NO release was nearly abolished by both treatments whereas
      BK still elicited partial NO release after eNOS/cyclooxygenase inhibition
      (P<0.001) but not after EL. In conclusion, OFR severely impair NO-mediated
      coronary vasorelaxation affecting both basal and agonist-evoked NO release but
      not eNOS activity. However, EL also significantly blunts NOS/COX-independent
      vasodilation suggesting alteration of other vasodilatative pathways.

PMID- 11341237
TI  - Back to the future.

PMID- 11341238
TI  - Treating 'mannequins'.

PMID- 11341239
TI  - Why expand the role of dental staff members?

PMID- 11341240
TI  - NY, ME hospitals handle emergencies well; but weaknesses are noted.

PMID- 11341241
TI  - Models of clinical infusional brachytherapy.

PMID- 11341242
TI  - In regard to Zurlo et al., IJROBP 2000;48:277-288.

PMID- 11341243
TI  - Cooperative research group members question advertisement.

PMID- 11341244
TI  - Near 10-year and longer periods modulate circadians: intersecting anti-aging and
      chronoastrobiological research.
AB  - Biological cycles with relatively long and some unusual periods in the range of
      the half-week, the half-year, years, or decades are being discovered. Their prior
      neglect constituted a confounder in aging and much other research, which
      then"flew blind" concerning the uncertainties associated with these cycles when
      they are not assessed. The resolution of more about 10-year and other cycles,
      some reported herein, replaces the admission of complete unpredictability,
      implied by using the label "secularity." Heretofore unaccounted-for variability
      becomes predictable insofar as it proves to be rhythmic and is mapped
      systematically to serve as a battery of useful reference values. About 10-year
      cycles in urinary 17-ketosteroid excretion and in heart rate and its variability,
      among others, are aligned with cycles of similar length in mortality from
      myocardial infarction. Associations accumulate between cycles of natural physical
      time structures, chronomes such as the 10.5-year (circadecennian) Schwabe and the
      21-year (circavigintunennian) Hale cycles of solar activity, and chronomes in
      biota. There are about 50-year (circasemicentennian) cycles in mortality from
      stroke in Minnesota and in the Czech Republic and also in human morphology at
      birth, the latter result reducing the likelihood that these cycles are purely
      human made. Associations among large populations warrant long-term systematic
      coordinated sampling of natural physical and biological variables of interest for
      the design of countermeasures against already documented elevated risks of
      stroke, myocardial infarction, and other catastrophic diseases, notably in
      elderly adults. New findings will be introduced against the background of the
      documented value of mapping rhythms in medicine and gerontology. In both these
      fields, rhythms promise the seeming paradox of better care for less.

PMID- 11341245
TI  - [The measurement of end-tidal carbon dioxide (PETCO2) is not a significant
      parameter to monitor in patients with severe traumatic brain injury].
AB  - PURPOSE: To evaluate the agreement between end-tidal carbon dioxide (PETCO2) and
      arterial CO2 (PaCO2) in patients with traumatic brain injury and to document the
      course of the (PaCO2-PETCO2) gradient over time. METHODS: Twenty one traumatic
      brain injury patients (Coma Glasgow Scale < or = 8) were included in this
      prospective observational study over a period of six months. Simultaneous
      determinations of PaCO2 and PETCO2 (by infrared capnometry) were recorded.
      Agreement between PaCO2 and PETCO2 was determined by the statistical method
      described by Bland and Altman. Changes in PETCO2 over time were compared with
      changes in PaCO2. Factors likely to explain a gradient superior to +/- 4 mmHg
      were explored. RESULTS: One hundred and eleven data pairs were obtained. The bias
      was 5.5 mmHg with a precision of 5.1 mmHg and limits of agreement ranged from 
      4.5 mmHg to 15.5 mmHg. The latter exceeded the predefined limits of agreement
      established to determine interchangeability between methods (+/- 4 mmHg). PETCO2
      and PoCO2 changed in opposite directions in 20% of 90 consecutive measurements.
      Only the duration of ventilation was found to be significantly associated with a
      gradient superior to +/- 4 mmHg. CONCLUSIONS: In this selected population of
      patients with severe traumatic brain injury, measurements of PETCO2 and PaCO2 are
      not interchangeable. Further the PoCO2-PETCO2 gradient is not stable over time
      and cannot predict variations of PaCO2. The use of PETCO2 instead of PaCO2 could
      be deleterious in patients in whom strict control of PaCO2 values is required.

PMID- 11341246
TI  - On alcohol consumption and all-case mortality.

PMID- 11341247
TI  - A new cognitive behavioural approach to the treatment of obesity.
AB  - While behavioural approaches to the management of obesity are often successful in
      achieving clinically significant weight loss, the weight lost is generally
      regained. The great majority of patients return to their pre-treatment weight
      within 3 years. There have been attempts to improve the long-term effectiveness
      of behavioural treatment but the results have been disappointing. In this paper
      we suggest that, among other factors, this is because of the neglect of the
      contribution of cognitive factors to weight regain, and because there is often
      ambiguity over the goals of treatment. We present a cognitive behavioural
      analysis of the processes involved in weight regain, and we describe a new
      cognitive behavioural treatment derived from it. This treatment is designed to
      minimise the problem of weight regain by addressing psychological obstacles to
      the acquisition of, and long-term adherence to, effective weight-control
      behaviour.

PMID- 11341248
TI  - On the scientific status of cognitive appraisal models of anxiety disorder.
AB  - The cognitive paradigm for understanding and treating anxiety disorders comprises
      two distinct and potentially incompatible approaches: appraisal and information
      processing. Advocates of the latter approach have sharply criticized the
      scientific adequacy of the appraisal models popularized by cognitive therapists.
      The purpose of this essay is to provide a reappraisal of these critiques of
      appraisal, and to defend an argument for methodological pluralism.

PMID- 11341249
TI  - Hopelessness depression as a distinct dimension of depressive symptoms among
      clinical and non-clinical samples.
AB  - Subtyping depression has been an interest of theorists and clinicians for at
      least four centuries. In this paper, we examined the validity of the symptom
      cluster component of the hopelessness theory of depression. We used structural
      equation modeling analyses on large samples of psychiatric outpatients (N=1604,
      844, and 680) and Air Force cadets (N=1404) who completed the items of the Beck
      Depression Inventory (BDI). Findings were supportive of the hopelessness
      depression cluster as a distinct depressive syndrome. Implications for the
      nosology of depression and for depression theory were discussed.

PMID- 11341250
TI  - The thought-action fusion scale: further evidence for its reliability and
      validity.
AB  - Thought-action fusion (TAF) refers to a set of cognitive biases that are thought
      to play a role in the development of obsessional phenomena. To measure these
      biases, R. Shafran, D. S. Thordarson, and S. Rachman (1996; Journal of Anxiety
      Disorders, 10, 379-391) developed the TAF-scale. They concluded that the TAF
      scale possesses adequate psychometric qualities. The current study sought to
      further explore the reliability and validity of the TAF-scale. Results indicate
      that the TAF-scale has good internal consistency. TAF-scores correlated with self
      reports of obsessional problems. Furthermore, mean scores in a mixed sample of
      anxiety disordered patients were higher than those in a normal sample. However,
      temporal consistency was somewhat disappointing. Also, the question remains
      whether TAF is specific to obsessive-compulsive disorder or taps more pervasive
      biases that play a role in a variety of disorders.

PMID- 11341251
TI  - How do trigger factors acquire the capacity to precipitate headaches?
AB  - This study tested two contrasting theories of how trigger factors acquire the
      capacity to precipitate headaches. The sample consisted of 110 participants, of
      whom 48 suffered from regular headaches. Participants were exposed to a validated
      headache trigger factor for one of five exposure durations. The trigger used was
      "visual disturbance" (flicker, glare and eyestrain) induced by a very bright,
      stroboscopic light. Response to the stimulus was measured by participant ratings
      of the degree of visual disturbance and head pain caused by the stimulus. As
      expected, the headache sufferers experienced more visual disturbance and head
      pain in response to the stimulus than the non-headache individuals. Longer
      exposure to the stimulus was associated with a subsequent reduction in pain
      ratings in response to the stimulus. This desensitization effect supported an
      avoidance model of how trigger factors acquire the capacity to precipitate
      headaches. The findings of this study have implications for the etiology of
      headache disorders. Also, the findings imply that the traditional clinical advice
      that the best way to prevent migraine and headache is to avoid the factors that
      trigger them, may be counterproductive, as any short-term gains may be more than
      wiped out by decreased tolerance for the trigger factors.

PMID- 11341252
TI  - Protective and vulnerability factors of depression in normal adolescents.
AB  - The present study investigated the role of various protective and vulnerability
      factors in the development of depressive symptoms. A sample of normal adolescents
      (N=373) completed the Children's Depression Inventory and measures of a negative
      attributional style, parental rearing behaviour, coping styles, and perceived
      self-efficacy. In addition to computing the correlations between depression and
      these protective and vulnerability factors, the present data were also subjected
      to structural equations modelling to examine the correlational structure of the
      data. Depression was accompanied by high levels of parental rejection, negative
      attributions, and passive coping, and by low levels of active coping and self
      efficacy. Furthermore, a model in which negative parental rearing behaviour and a
      negative attributional style featured as the primary sources of depression, while
      coping styles and self-efficacy played a mediating role in the formation of
      depressive symptoms, provided a reasonable fit for the data.

PMID- 11341253
TI  - Psychological vulnerabilities in patients with major depression vs panic
      disorder.
AB  - The tripartite model (Clark & Watson, 1991: Clark, L. A., & Watson, D. (1991).
      Tripartite model of anxiety and depression: Psychometric evidence and taxonomic
      implications. Journal of Abnormal Psychology, 100, 316-336) posits that anxiety
      and depression share nonspecific features of neuroticism but that somatic arousal
      appears unique to anxiety, and low positive affect appears unique to depression.
      The present study controlled for these higher-order effects and evaluated the
      relative contributions of four, specific lower-order vulnerabilities (anxiety
      sensitivity, rumination, self-criticism, self-oriented perfectionism).
      Participants were 38 depressed patients and 38 patients with panic disorder
      matched as closely as possible for age and gender, and all were diagnosed using
      the same structured interview by an experienced clinician. Results from
      hierarchical logistic regression analysis were consistent with predictions from
      the tripartite model in that only the unique features of arousal and positive
      affectivity differentiated the two diagnostic groups. At a lower-order level,
      only anxiety sensitivity (and its facet of fear of physical symptoms) and a
      ruminative response style demonstrated incremental predictive ability. The
      discussion focuses on the relationships among these higher-order and lower-order
      variables, and their potential importance for understanding specific
      manifestations of psychopathology.

PMID- 11341254
TI  - The myth of DSM's invention of new categories of disorder: Houts's diagnostic
      discontinuity thesis disconfirmed.
AB  - Houts (2001) argues that increases in DSM diagnostic categories are due to the
      invention of new disorders that are discontinuous with old conceptions of
      disorder and would not have been previously diagnosed. He maintains that DSM
      category increases are not comparable in nature to ICD category increases, which
      are mainly refinements of recognized disorders. I survey categories of disorder
      introduced after DSM-II and assess whether they are discontinuous with old
      concepts and categories of disorder. Candidate categories are identified from:
      Houts and Follette (1998), Mentalism, mechanisms, and medical analogues: Reply to
      Wakefield. Journal of Consulting and Clinical Psychology; Kutchins and Kirk
      (1997) Making us crazy: DSM: The psychiatric bible and the creation of mental
      disorders. New York: Free Press; and my own list. The result is that virtually
      none of the candidate categories are invented, discontinuous categories. In
      almost every case, the newly labeled conditions were considered disorders at the
      time of DSM-II and would have been diagnosed under DSM-II categories. I also
      reexamine DSM-IV sleep disorder categories, which Houts claims are discontinuous
      with past diagnostic conceptions. The result is that all DSM-IV sleep disorders
      were recognized as disorders at the time of DSM-II, and most were recognized as
      mental disorders. I conclude that DSM category increases are comparable in nature
      to ICD category increases, and that the invention-of-disorder account cannot
      explain the vast majority of such increases.

PMID- 11341255
TI  - Eating disorder examination questionnaire: norms for young adolescent girls.
AB  - This paper reports young adolescent female norms for the Eating Disorder
      Examination Questionnaire (EDE-Q). The standardization sample was comprised of
      808 girls aged between 12 and 14 years from three single-sex schools (one private
      and two state schools). Means, standard deviations and percentile ranks for raw
      EDE-Q subscale scores are presented. Prevalence figures for key eating disorder
      behaviors over the previous two weeks were as follows: 4% self-induced vomiting;
      1% laxative misuse; 0.4% diuretic misuse; and 8% regular binge eating.

PMID- 11341256
TI  - A better future for European science?

PMID- 11341258
TI  - Astrophysics. Echoes of the big bang put theories in tune.

PMID- 11341257
TI  - Genome sequencing. Celera assembles mouse genome; public labs plan new strategy.

PMID- 11341259
TI  - Quantum physics. Loopy electron model solves ion mystery.

PMID- 11341260
TI  - Technology. Liquid crystal displays rub out the rub.

PMID- 11341261
TI  - Digital security. Music industry strikes sour note for academics.

PMID- 11341262
TI  - Origins of BSE. Intriguing clues to a scrapie-mad cow link.

PMID- 11341263
TI  - Science and commerce. Few authors disclose conflicts, survey finds.

PMID- 11341264
TI  - French universities. Reform plan seen as halting step.

PMID- 11341266
TI  - Lobbying. Can ASTRA restore a glow to the physical sciences?

PMID- 11341265
TI  - Lobbying. Perfecting the art of the science deal.

PMID- 11341267
TI  - Lobbying. Tools of the trade.

PMID- 11341269
TI  - Lobbying. Hawaii rides a wave of research earmarks.

PMID- 11341268
TI  - Lobbying. Faces in the crowd.

PMID- 11341270
TI  - Albania. Physicist-President battles ethnic wars and illiteracy.

PMID- 11341271
TI  - Society of Toxicology meeting. Toxicologists hit the West Coast.

PMID- 11341273
TI  - Geodynamics. A lively or stagnant lowermost mantle?

PMID- 11341272
TI  - Cell biology. New clue to how the cell controls its proteins.

PMID- 11341274
TI  - Continuing research into Gulf War illness.

PMID- 11341275
TI  - Continuing research into Gulf War illness.

PMID- 11341276
TI  - Statistics: what seems natural?

PMID- 11341277
TI  - The bioenergetics of the immune system.

PMID- 11341278
TI  - A metaphor for the map.

PMID- 11341279
TI  - Essays on science and society. The end for Indonesia's lowland forests?

PMID- 11341280
TI  - Apoptosis. Death of a monopoly?

PMID- 11341281
TI  - Putting liquids under molecular-scale confinement.

PMID- 11341282
TI  - Ribosome structure. The ribosome in action.

PMID- 11341283
TI  - Interstellar chemistry. Tunneling reactions in interstellar ices.

PMID- 11341284
TI  - Paleoclimate. CO2 and climate change.

PMID- 11341285
TI  - Neuroscience. Unwrapping glial cells from the synapse: what lies inside?

PMID- 11341286
TI  - Impact of trace metals and nutrients levels on phytoplankton from the Kuwait
      coast.
AB  - The impact of marine pollution was estimated from seven stations of Kuwait
      coastal waters. The mean concentrations of all trace metals in seawater (0.07
      7.04 microg/l) and in phytoplankton (14.90-52.01 microg/g) revealed less
      phytoplankton abundance in Stations IV VI during the four seasons. However, a
      relative surge in the phytoplankton abundance, with an increase in the mean
      concentrations of all trace metals in seawater (0.15-8.94 microg/l) and
      phytoplankton (22.82-61.25 microg/g), was observed in Station II. A low
      phytoplankton abundance was noted in Stations I, III, and VII despite low mean
      concentrations of all the trace metals in seawater (0.11-5.77 microg/l) and
      phytoplankton (1.40-20 microg/g) during the four seasons. Statistical tests
      revealed significant difference in Fe, Ni, and Pb between the four seasons in
      seawater and Fe and Co in phytoplankton. No significant difference in trace
      metals between locations was observed in seawater and in phytoplankton. The major
      nutrients in all the four seasons were found in the magnitude of SiO3 > NO3 > PO4
      in all the stations, and thus, support the presence of rich diatoms and
      dinoflagellates than other phytoplankton groups. The seven stations also
      represented indicator species of oil and industrial waste pollution.

PMID- 11341287
TI  - Monitoring natural organic matter in water with scanning spectrophotometer.
AB  - This study uses scanning ultraviolet-visible (UV-Vis) spectrophotometer to
      monitor natural organic matter (NOM) in water. The results showed that the area
      under the UV-Vis spectra is a good surrogate to monitor the concentration of the
      aqueous NOM. No apparent difference was found between the spectra of the three
      commercially available humic acids used in this study. The use of the scanning
      spectra compensates the potential random error in the absorbance determined at
      single wavelength due to the heterogeneous NOM compositions. The major
      interference of the proposed method comes from the formazine turbidity and
      nitrate nitrogen (NO3- -N). Although filtration with a 0.45-microm filter can
      remove most of the interference from formazine, some interference is still
      present at a wavelength less than 250 nm. Also it is found that the presence of
      the NO3- -N greatly affect the spectra of the NOM. In order to monitor the NOM in
      water with minimized interference, it is recommended that the area under the
      spectra between 250 and 350 nm should be used as a surrogate for concentration of
      NOM in water.

PMID- 11341288
TI  - Surface ozone trends in Hong Kong in 1985-1995.
AB  - Ozone trends in Hong Kong were assessed from the ozone data recorded at three
      urban stations and one station in the new development area. Three parameters were
      selected as the robust trend indicators in the study: monthly mean, monthly
      averaged daily 1-h maximum, and number of annual hours > 120 microg m(-3). As the
      ozone data displayed obvious seasonal variation, using deseasonalized monthly
      average parameters to estimate the ozone trends could smooth out the influence of
      seasonal fluctuations. The detection of an increase of more than 10% per year in
      ozone concentration at one station was particularly alarming. Effects of
      meteorological factors, control programmes of ozone precursors, and long-range
      transport on the ambient ozone level were examined in the study.

PMID- 11341289
TI  - The relationship of dissolved Pb to some dissolved trace metals (Al, Cr, Mn, and
      Zn) and to dissolved nitrate and phosphate in a freshwater aquatic system in
      Mauritius.
AB  - The relationship of some dissolved trace metals (Al, Cr, Mn, Zn, and Pb) with one
      another and to dissolved phosphate and nitrate in a freshwater aquatic system at
      Flic en Flac and Grand River North West (GRNW) in Mauritius (1850 km2, 20 degrees
      S and 57 degrees E, Western Indian ocean) is reported following trace metal
      determination using inductively coupled plasma mass spectrometry (ICP-MS).
      Dissolved Al (<200 ng ml(-1)), Cr (<50 ng ml(-1)), Mn (<50 ng ml(-1)), Zn (< 100
      ng ml(-1)), and Pb (<50 ng ml(-1)) upstream, downstream GRNW and in the marshes
      and rivulet at Flic en Flac were found to be below the recommended EEC maximum
      admissible concentrations and within the ambient drinking water quality standards
      in Mauritius. Dissolved Pb was significantly positively correlated to both
      dissolved Cr and Zn suggesting that the cycling for dissolved Pb is linked to the
      cycling of both dissolved Cr and Zn along GRNW. The common influential cycling of
      Pb and Zn was further reinforced as both dissolved Pb and Zn were significantly
      positively correlated to dissolved phosphate, which suggested a biological role
      in the cycling of Zn and Pb. The role of biological activity or adsorption to
      biological systems in Pb cycling along GRNW is further suggested as dissolved Pb
      was significantly correlated to dissolved nitrate. The apparent absence of the
      dissolved Al, Cr, and Mn with dissolved nitrate and phosphate could be attributed
      to factors such as the lower sensitivity of the GRNW to metal uptake during
      biological activity during the time frame considered. The cycling of dissolved Al
      and Mn was also not linked to the cycling of Cr, Zn, and Pb as no significant
      correlation was found along GRNW.

PMID- 11341290
TI  - Assessment of organochlorine pesticide residue levels in dairy milk and buffalo
      milk from Jaipur City, Rajasthan, India.
AB  - The widespread application of pesticides in agriculture, public health, and
      industry and in and around the home can result in the accumulation of pesticides
      in the environment. Therefore, a survey has been conducted during 1993-1996 to
      investigate the magnitude of contamination of bovine milk with organochlorine
      pesticide (OCP) residues from Jaipur City, Rajasthan, India. Milk samples, i.e.,
      dairy (toned and whole) and buffalo milk, were collected seasonally, and
      pesticide residues were assessed using a gas chromatograph (GC) with an electron
      capture detector (ECD). The results indicate that all the milk samples were
      contaminated with dichlorodiphenyltrichloroethane (DDT) and its metabolites (DDE
      and p,p'-dichlorodiphenyldichloroethane [DDD]), isomers of hexachlorocyclohexane
      (HCH; alpha, beta, and gamma), heptachlor and its epoxide, and aldrin. Seasonal
      variations of these pesticide residue levels were also observed in all the milk
      samples. Samples collected during winter season were found to contain higher
      residue levels as compared to other seasons.

PMID- 11341291
TI  - Denitrification with acrylonitrile as a substrate using pure bacteria cultures
      isolated from acrylonitrile-butadiene-styrene wastewater.
AB  - This study attempted to isolate and identify the denitrifying bacteria that
      utilize acrylonitrile as a substrate from acrylonitrile-butadiene-styrene (ABS)
      resin wastewater. The performance of the denitrifying bacteria for treating
      different initial acrylonitrile concentrations was also investigated under anoxic
      conditions. The results showed that seven strains of denitrifying bacteria that
      can use acrylonitrile or acrylic acid as a substrate were isolated from the
      denitrification tank of a wastewater treatment plant in a ABS resin manufacturing
      plant and a lab-scale anoxic granular activated carbon-fluidized bed. The
      bacteria strains Acidovorax facilis B and Pseudomonas nautica could utilize
      acrylonitrile up to 279 mg/l as a substrate for denitrification. For complete
      nitrate removal, an adequate supply of acrylonitrile was necessary. Under the
      assumption that the acrylic acid would be completely removed, the removal of 1
      mg/l nitrate by A. facilis B or P. nautica, about 0.64-0.74 mg/l acrylonitrile or
      0.87-1 mg/l acrylic acid was needed. Because strains A. facilis B and P. nautica
      could utilize acrylonitrile for denitrification, they are expected to play an
      important role in the treatment of acrylonitrile in the wastewater treatment
      plant (denitrification and nitrification processes) and lab-scale granular
      activated carbon-fluidized bed.

PMID- 11341292
TI  - Heavy metal levels in the sediments of four Dar es Salaam mangroves. Accumulation
      in, and effect on the morphology of the periwinkle, Littoraria scabra (Mollusca:
      Gastropoda).
AB  - Heavy metals were determined in the soft tissue and shells of the littorinid,
      Littoraria scabra, and in the sediments of four mangrove areas along the Dar es
      Salaam coastline where L. scabra was collected. Several metals accumulate,
      preferentially in the animals' soft body parts, but do not seem to affect the
      shell morphology of this species. Sediment-metal levels, measured in the direct
      vicinity of Dar es Salaam have increased dramatically over the last decade.
      Nonetheless, these levels are still lower compared to metal-sediment levels
      reported in polluted European and American estuaries. Soft-tissue metal levels
      detected in L. scabra are, nevertheless, with the exception of Cr and Zn,
      comparable to metal levels reported in other gastropod species.

PMID- 11341293
TI  - Trace and major element pollution originating from coal ash suspension and
      transport processes.
AB  - Coal ash obtained by coal combustion in the "Nikola Tesla A" power plant in
      Obrenovac, near Belgrade, Yugoslavia, is mixed with water of the Sava river and
      transported to the dump. In order to assess pollution caused by leaching of some
      minor and major elements during ash transport through the pipeline, two sets of
      samples (six samples each) were subjected to a modified sequential extraction.
      The first set consisted of coal ash samples taken immediately after combustion,
      while the second set was obtained by extraction with river water, imitating the
      processes that occur in the pipeline. Samples were extracted consecutively with
      distilled water and a 1 M solution of KCl, pH 7, and the differences in
      extractability were compared in order to predict potential pollution. Considering
      concentrations of seven trace elements as well as five major elements in extracts
      from a total of 12 samples, it can be concluded that lead and cadmium do not
      present an environmental threat during and immediately after ash transport to the
      dump. Portions of zinc, nickel and chromium are released during the ash
      transport, and arsenic and manganese are released continuously. Copper and iron
      do not present an environmental threat due to element leaching during and
      immediately after the coal ash suspension and transport. On the contrary, these
      elements, as well as chromium, become concentrated during coal ash transport.
      Adsorbed portions of calcium, magnesium and potassium are also leached during
      coal ash transport.

PMID- 11341294
TI  - The effects of FeCl3 on the distribution of the heavy metals Cd, Cu, Cr, and Zn
      in a simulated multimetal incineration system.
AB  - Recognizing that waste-derived chlorine can enhance heavy metal emissions by
      forming volatile metallic chlorides during municipal solid waste (MSW)
      combustion, and that in Taiwan, FeCl3-containing sewage sludge may either be
      landfilled or coincinerated with other MSW, this study thus investigated the
      effects of FeCl3 on the speciation and partitioning of heavy metals in a
      multimetal incineration system by using a tubular furnace and FeCl3-spiked
      simulated wastes. The molar ratio of chlorine content to heavy metal content
      (referred to as the Cl/ M ratio), ranging from 3 to 200, was used as a parameter
      to evaluate the effects of chlorine on the movement of heavy metals between the
      incinerator discharges. Results indicate that speciation and partitioning were
      related to the affinity between the chlorine and the heavy metals and between
      chlorine and hydrogen in the combustion system. The effectiveness of increasing
      the Cl/M ratio to the formation potential of metallic chlorides and on the shift
      of heavy metals from the bottom ash to the fly ash and/or the flue gases was
      found to have in increasing order as follows: Zn>Cu>Cr, a phenomenon basically
      reflecting the volatility of the heavy metals and their chlorides formed during
      combustion.

PMID- 11341295
TI  - Heavy metal anomalies in lagoon sediments related to intensive agriculture in
      Altata-Ensenada del Pabellon coastal system (SE Gulf of California).
AB  - Heavy metal concentrations were examined in surface sediments from 79 sites
      within the Altata-Ensenada del Pabellon lagoon system. Data were normalized to
      separate natural from anthropogenic factors using aluminum and lithium as
      conservative elements and following two different discriminating criteria. For
      the normalization process, the natural metal concentrations were assumed to vary
      consistently with aluminum and lithium, unless the metal contents were of human
      origin. Strong linear correlations (P < .001) were observed between the
      conservative elements and the metals measured. According to Szefer's normalizing
      criteria, about 90% of the polluted sites, for at least one metal, occurred near
      agricultural discharge drains. In accordance with the Muller [Umschau 79 (1979)
      778.] scale, this lagoon system is subject to pollutant effects only with regard
      to Pb (moderately to strongly polluted). It was concluded that either Al and Li
      could be useful to normalize granulometric variability in heavy metal studies of
      these lagoon sediments, and that Summers' normalization criterion proved more
      rigorous than Szefer's for these types of sediments.

PMID- 11341296
TI  - Heavy metal contamination of brown seaweed and sediments from the UK coastline
      between the Wear river and the Tees river.
AB  - The concentration of Fe, Mn, Zn, Cu, Pb, Ni, Cr, Cd, and Ag were determined in
      the brown alga Fucus vesiculosus and intertidal surface sediments from coastal
      locations of northeast England. Levels of heavy metals similar to those of
      polluted areas of the British coastline were detected. There is evidence of
      contamination (especially with Zn and Pb) in sediments from sites affected by
      colliery spoil and from the Wear estuary. The pelitic fraction ( < 63 microm) is
      usually more enriched in heavy metals, but it represents a very small percentage
      of the bulk samples. The fine-grained sand is a very important repository of
      contaminants especially where particles of colliery spoil, secondary mineral, and
      amorphous phases are present. Aqua regia-extracted Zn, Cu, and Pb in sediments
      are significantly correlated with those in seaweed. Despite the closure of all
      base metal and coal mines, and the cessation of many industrial activities in the
      region, sediments and brown algae are contaminated with heavy metals. The control
      site (Holy Island) and the Tees estuary appear to be the least affected.

PMID- 11341297
TI  - GG-genotype in the promotor region of uncoupling-protein-1 gene is associated
      with lower level of dehydroepiandrosterone in type 2 diabetes.
AB  - The A-->G (-3826) point mutation within the distal region of the uncoupling
      protein-1 (UCP-1) promoter is possibly involved in the development of obesity,
      diabetes and related disorders. DHEAS has been found to stimulate expression of
      UCP-1-mRNA. The aim of our study was to evaluate the prevalence of the three UCP
      1 genotypes in type 2 diabetic patients out of a population based sample.
      Possible associations of A-->G mutation with serum levels of DHEAS and with
      obesity, diabetes and retinopathy were examined. - In 549 diabetic patients (312
      males and 237 females) out of a population-based sample UCP-1 genotype was
      determined by genomic PCR and Bcl-I-RFLP analysis. Serum levels of DHEAS were
      measured by ELISA. - Genotype frequencies were: GG genotype, 4.4% (n= 24); AG
      genotype 37.3% (n=205) and AA genotype 58.3% (n= 320). The genotype groups were
      comparable with respect to sex, BMI, HbA1c, systolic blood pressure (BP),
      retinopathy and also to serum levels of C-peptide, leptin and cortisol. Serum
      levels of DHEAS were lowest in GG-genotype as compared to AG and AA (GG: 1.8+/
      1.5 micromol/l, AG: 2.2+/-1.8 micromol/l, AA: 2.6+/-2.1 micromol/l; AA vs AG, AA
      vs GG: p<0.05). In a multiple linear regression analysis, which controlled for
      age, C-peptide, cholesterol, systolic BP, BMI, and HbA1c DHEAS was significantly
      negatively correlated with levels of cholesterol and positively with systolic BP
      only in females (p<0.05). - Allelic frequency for G in diabetic subjects was 0.23
      which was similar as compared to a non-diabetic population examined by us in an
      earlier study. GG-genotype was associated with low levels of DHEAS in diabetic
      patients but not with retinopathy. We suggest a role for UCP-1 polymorphism in
      the pathogenesis of obesity and arteriosclerosis. This hypothesis, however, needs
      further investigation.

PMID- 11341298
TI  - Analysis of TGFbeta3 gene expression and protein levels in human bone and serum.
AB  - Recent data indicate that TGFbeta3, one member of the TGFbeta-isoforms, has an
      important role in bone remodeling. Up to date little is known about the
      expression and regulation of TGFbeta3 in man. We established a highly specific
      ELISA for quantitative measurement of TGFbeta3 in bone and blood samples and a RT
      PCR in combination with HPLC for detection and quantification of TGFbeta3 mRNA in
      89 human bone samples. Levels of TGFbeta3 protein ranged between 30 and 66 pg/mg
      bone (mean 36,6 +/-1,03 pg/mg) and between 30 and 1910 pg/ml in serum (mean
      128.9+/-38.9 pg/ml). TGFbeta3 mRNA expression as well as protein levels in serum
      and in bone declined age dependently. No specific load- or site-specific
      distribution of TGFbeta3 mRNA expression or protein content was detected at
      different sites indicating an absence of mechanical regulation. Protein levels of
      TGFbeta3 in serum correlated with TGFbeta3 mRNA expression in bone (p= 0.0027;
      r=0.49). By contrast, TGFbeta3 protein levels stored in the bone matrix were not
      related to TGFbeta3 mRNA reflecting the long term process of TGFbeta3 deposition
      during bone remodeling. Notably TGFbeta3 serum levels were highly correlated with
      IGF-I and osteocalcin levels in serum. We conclude that TGFbeta3 in man
      circulates in significant amounts which appears to be representative for TGFbeta3
      expression in bone tissue and may be in part derived from bone. The high
      correlation of TGFbeta3 with IGF-I suggests parallel systemic principles of
      regulation.

PMID- 11341299
TI  - Macroencapsulation of rat islets without alteration of insulin secretion
      kinetics.
AB  - Transplantation of encapsulated islets may restore endogenous insulin secretion
      in type 1 diabetics with no need of lifetime immunosuppression of the recipient.
      A biomaterial should be developed which combined immunoisolation with rapid and
      efficient diffusion of glucose and insulin. Rat islets were macroencapsulated in
      capillaries (molecular cut off 50 kD) of differently modified polysulphone.
      Macroencapsulated islets were perifused to study the kinetics of glucose induced
      insulin secretion into the perifusion medium. Blending polysulphone (PSU) with
      poly vinyl pyrrolidone or sodium dodecyl sulphate was not suited for islet
      macroencapsulation since glucose induced insulin release was absent after
      encapsulation. Hydroxy methylation (CH2OH) of PSU improved the secretory
      behaviour of macroencapsulated islets depending on the degree of substitution
      (DS). At 0.8 DS glucose induced insulin secretion was delayed and inefficient. At
      maximal degrees of PSU-substitution (1.8) the kinetics of insulin release and the
      efficiency of insulin release were very similar to that observed of free floating
      islets. In conclusion, highly substituted hydroxy methylated polysulphone allows
      a rapid and efficient insulin release after macroencapsulation and is suited for
      the further development of a bioartificial pancreas.

PMID- 11341300
TI  - Fatigue and hyponatremia in a 75-year-old woman: unusual presentation of
      hypophysitis.
AB  - A 75-year-old woman presented with general fatigue progressing to somnolence.
      Laboratory tests showed marked hyponatremia. TSH in the normal range, but low
      levels of free T3 and free T4. Evaluation of pituitary hormones and magnetic
      resonance imaging of the pituitary unmasked findings characteristic for
      hypophysitis with secondary adrenal insufficiency and secondary hypothyroidism.
      Hormonal substitution with hydrocortisone and levothyroxine resulted in rapid
      improvement of all symptoms and signs. Without additional treatment shrinkage of
      the pituitary gland could be documented. Our report extends the known clinical
      and pathological spectrum of hypophysitis and illustrates the need to include
      this uncommon entity in the differential diagnosis of hyponatremia even in
      elderly patients.

PMID- 11341301
TI  - Reproductive functions, fertility and genetic risks of ageing men.
AB  - The changes of reproductive functions, fertility and genetic risks of ageing
      females have been investigated relatively intensively. The state of knowledge
      about endocrine and reproductive changes in ageing men as well as possible age
      related paternal genetic risks lags far behind. In general serum testosterone
      levels decrease with increasing age. In ageing men testis morphology and semen
      production can be absolutely normal. However, in some testes degenerative forms
      of germ cells can be observed. Fertility may be maintained up to a very high age.
      The genetic quality of sperm produced by older men may be reduced for several
      reasons, among which age-related increases in germ cell mutations, impairment of
      DNA-repair mechanisms and apoptotic processes are the most likely. The incidence
      of several autosomal dominant diseases, such as achondroplasia, polyposis coli,
      Marfan syndrome, Apert syndrome or basal cell naevi is associated with advanced
      paternal age, whereas there is no clear evidence for a paternal effect on
      structural or numeric chromosome anomalies. Hence even if offspring of older men
      have a slightly increased incidence of certain genetic diseases, the individual
      risk of such a new disease must be considered as extremely small, as the
      incidence of these diseases is very low.

PMID- 11341302
TI  - Intraadrenal mechanisms of DHEA regulation: a hypothesis for adrenopause.
AB  - Dehydroepiandrosterone (DHEA) and its sulfate metabolite DHEAS are the major
      androgens secreted by the human adrenal gland. The specific control of these
      hormones remains unclear. While ACTH is a potent stimulator of DHEA secretion,
      other factors both systemic and local have been involved in adrenal androgen
      control. Here we review the extra and intraadrenal regulation of DHEA and propose
      a hypothetical model for adrenal senescence.

PMID- 11341303
TI  - Oxytocin in the male: an old hormone growing sexy with age.
AB  - It has long been a mystery of oxytocin research that males have similar levels of
      the hormone in their blood as females, but there is no known function associated
      with this. This review brings together some diverse literature to point out a
      possible role of oxytocin in the context of stress and sexuality.

PMID- 11341304
TI  - Vitamin D status, trunk muscle strength, body sway, falls, and fractures among
      237 postmenopausal women with osteoporosis.
AB  - The aim of this study was to identify factors associated with fractures in
      patients with postmenopausal osteoporosis. The overall hypothesis was that trunk
      muscle strength, body sway and hypovitaminosis D would influence daily activities
      and the likelihood of falls and fractures. - In 237 women (mean age 62.9+/-7.4
      years) osteoporosis was defined by a T-score at the femoral neck below -2.5 SD.
      Trunk muscle strength was determined using isokinetic dynamometry and body sway
      was measured according to Lord et al. Limitations in everyday life were assessed
      and the history of falls was documented. A fracture was defined as a vertebral
      height reduction of more than 20% or at least 4 mm. The assessment was carried
      out using the Spine Deformity Index (SDI) and was confirmed by an experienced
      radiologist. Pearson coefficients of correlation were calculated. - After
      correction for age, significant associations were found for body sway and 25
      hydroxyvitamin D (p<0.001), body sway and falls (p<0.001), body sway and rib
      fractures (p<0.01), trunk muscle strength and limitations in everyday life
      (p<0.001), trunk muscle strength and SDI (p<0.001), trunk muscle strength and
      bone density (p<0.001), and bone density and 25-hydroxyvitamin D (p<0.001). No
      significant correlation was found for trunk muscle strength and 25-hydroxyvitamin
      D (p=0.712). - Findings suggest that hypovitaminosis D is associated with
      increased body sway and an elevated risk for falls and falls-related fractures.
      Musculoskeletal rehabilitation should include strengthening exercises for the
      trunk muscles and training of neuromuscular co-ordination and balance.

PMID- 11341305
TI  - Differential age-related changes of hypothalamus - pituitary - adrenal axis
      hormones in healthy women and men - role of interleukin 6.
AB  - Aging is accompanied by marked changes of steroid hormone levels which vary among
      women and men. The age-related increase of cytokines such as interleukin (IL)- 6
      may modulate the endocrine system. We aimed to investigate the role of IL-6 for
      the gender-specific changes of acrophase steroid hormone secretion in healthy
      subjects during aging. Out of 120 healthy subjects, 60 men and 48 women (non
      luteal phase) were recruited (age: 18 to 75 years). Age was positively correlated
      with IL-6 (female and male: p<0.001) and adrenocorticotropic hormone (ACTH) in
      women only (p<0.001). Age was negatively correlated with progesterone (female and
      male: p<0.001), cortisol (only female: p=0.003), androstenedione (female and
      male: p<0.001), but not 17OH progesterone. After correction for IL-6, the age
      related decrease of steroid hormones was blunted in both gender groups except for
      androstenedione (female and male: p<0.005). Furthermore, the ratio of serum
      cortisol to plasma ACTH decreased with age only in women but not in men (female:
      p< 0.001). Correction for IL-6 did not markedly change the negative
      interrelationship between age and the mentioned ratio in these women. However, a
      linear regression analysis revealed that the increase of ACTH in relation to
      cortisol depends on serum free testosterone in men (p=0.042) and on serum free 17
      beta-estradiol (p<0.001) together with serum IL-6 in women (p=0.021). In
      conclusion, IL-6 plays an important role for acrophase pituitary and peripheral
      hormone secretion in women only. The gender-specific changes of cortisol in
      relation to ACTH depend on the age-related decrease of the respective sex hormone
      in both gender groups and the increase of IL-6 in women. This study underlines
      the hormone-like role of IL-6 in the aging process of the endocrine system in
      women.

PMID- 11341306
TI  - Metabolic engineering.
AB  - Metabolic engineering has developed as a very powerful approach to optimising
      industrial fermentation processes through the introduction of directed genetic
      changes using recombinant DNA technology. Successful metabolic engineering starts
      with a careful analysis of cellular function; based on the results of this
      analysis, an improved strain is designed and subsequently constructed by genetic
      engineering. In recent years some very powerful tools have been developed, both
      for analysing cellular function and for introducing directed genetic changes. In
      this paper, some of these tools are reviewed and many examples of metabolic
      engineering are presented to illustrate the power of the technology. The examples
      are categorised according to the approach taken or the aim: (1) heterologous
      protein production, (2) extension of substrate range, (3) pathways leading to new
      products, (4) pathways for degradation of xenobiotics, (5) improvement of overall
      cellular physiology, (6) elimination or reduction of by-product formation, and
      (7) improvement of yield or productivity.

PMID- 11341307
TI  - Solid-state fermentation: a promising microbial technology for secondary
      metabolite production.
AB  - Solid state (substrate) fermentation (SSF) has been used successfully for the
      production of enzymes and secondary metabolites. These products are associated
      with the stationary phase of microbial growth and are produced on an industrial
      scale for use in agriculture and the treatment of disease. Many of these
      secondary metabolites are still produced by submerged liquid fermentations (SmF)
      even though production by this method has been shown to be less efficient than
      SSF. As large-scale production increases further, so do the costs and energy
      demands. SSF has been shown to produce a more stable product, requiring less
      energy, in smaller fermenters, with easier downstream processing measures. In
      this article we review an important area of biotechnology, since the recent
      evidence indicates that bacteria and fungi, growing under SSF conditions, are
      more than capable of supplying the growing global demand for secondary
      metabolites.

PMID- 11341308
TI  - Production of 3-nitrocatechol by oxygenase-containing bacteria: optimization of
      the nitrobenzene biotransformation by Nocardia S3.
AB  - Twenty-one microorganisms were screened for their ability to convert
      nitroaromatics into 3-nitrocatechol as a result of the action of an oxygenase.
      Cultures containing toluene dioxygenases and phenol monooxygenases accumulated 3
      nitrocatechol during incubation with nitrobenzene and nitrophenol, respectively.
      Nocardia S3 was selected and studied in more detail. Toluene-pregrown cultures
      were able to degrade nitrobenzene with a concomitant formation of 3
      nitrocatechol. The rates of nitrobenzene utilization decreased throughout the
      biotransformation period and finally the accumulation ceased. The gradual
      deterioration of the biotransformation rates was not a consequence of depletion
      of the NADH pool, but was due to the accumulation of 3-nitrocatechol. The
      inhibition of nitrobenzene biotransformation by 3-nitrocatechol greatly impacts 3
      nitrocatechol production processes.

PMID- 11341309
TI  - Involvement of branched-chain amino acid aminotransferases in the production of
      fusel alcohols during fermentation in yeast.
AB  - Organoleptic compounds produced by yeast during the fermentation of wort have a
      great impact on beer smell and taste. Among them, fusel alcohols are the major
      abundant volatile compounds. The availability of Saccharomyces cerevisiae mutants
      in which the genes coding for the two branched-chain amino acid aminotransferases
      have been deleted offers the possibility of further defining the role of these
      enzymes in the formation of higher alcohols. Comparing the production profiles of
      different strains, it is clear that they are not all influenced in the same way
      by branched-chain amino acid aminotransferase mutations. First of all, as
      propanol is synthesised from alpha-ketobutyrate, the first metabolic intermediate
      in the anabolic pathway of isoleucine, neither the eca39 nor eca40 mutations have
      any effect on the production of this higher alcohol. On the other hand, it can be
      concluded that the eca40 mutation has a drastic effect on the production of
      isobutanol. To a certain extent, the same conclusion can be made for the
      production of active amyl alcohol and isoamyl alcohol, although the results
      suggest that another route could lead to the formation of these two higher
      alcohols.

PMID- 11341310
TI  - Improved beta-thujaplicin production in Cupressus lusitanica suspension cultures
      by fungal elicitor and methyl jasmonate.
AB  - Production of a novel antimicrobial tropolone, beta-thujaplicin, in Cupressus
      lusitanica suspension cultures was studied by using a variety of chemicals and
      fungal elicitors. Sodium alginate, chitin, and methyl jasmonate resulted in 2-,
      2.5-, and 3-fold higher beta-thujaplicin production, respectively, than in the
      control. Significantly improved beta-thujaplicin production (187 mg l(-1)) was
      obtained using a high cell density (180-200 g l(-1)) and fungal elicitor
      treatment [10 mg (g fresh cells)(-1)] in a production medium with a high ferrous
      ion concentration (0.3 mM). This improved volumetric productivity was 3- to 4
      fold higher than obtained under standard conditions. A synergistic effect of
      fungal elicitor and ferrous ion on beta-thujaplicin production was also suggested
      by our study. Plant cell culture technology is a promising alternative for
      producing a large variety of secondary metabolites that are widely used as food
      additives, pharmaceuticals, and dairy products (Verpoorte et al. 1999). Thus,
      beta-thujaplicin production by plant cell cultures was developed with the goal of
      commercial application (Berlin and Witte 1988; Itose and Sakai 1997; Ono et al.
      1998). However, the production of beta-thujaplicin by plant cell cultures is
      still not competitive for use in industrial applications. In this study, we
      assessed the effects of methyl jasmonate, alginate, chitin, and fungal elicitor
      on beta-thujaplicin production; we obtained a significantly elevated beta
      thujaplicin production by using an improved culture strategy.

PMID- 11341311
TI  - Combination of Trichoderma harzianum endochitinase and a membrane-affecting
      fungicide on control of Alternaria leaf spot in transgenic broccoli plants.
AB  - Progeny from transgenic broccoli (cv. Green Comet) expressing a Trichoderma
      harzianum endochitinase gene were used to assess the interaction between
      endochitinase and the fungicide Bayleton in the control of Alternaria
      brassicicola. In vitro assays have shown synergistic effects of endochitinase and
      fungicides on fungal pathogens. Our study examined the in planta effects of
      endochitinase and Bayleton, individually and in combination. Two month old
      transgenic and non-transgenic plants were sprayed with ED50 levels of Bayleton
      and/or inoculated with an A. brassicicola spore suspension. Disease levels in non
      sprayed transgenic plants were not statistically different from sprayed
      transgenic plants nor from sprayed non-transgenic controls. Thus endochitinase
      transgenic plants alone provided a significant reduction of disease severity,
      comparable to the protection by fungicide on non-transgenic plants. Comparison of
      the expected additive and observed effects revealed no synergism between
      endochitinase and Bayleton (at ED50 level), and usually less than an additive
      effect. Some transgenic lines sprayed with fungicide at doses higher than ED50
      showed resistance similar to the non-sprayed transgenic lines, again suggesting
      no synergistic effect. Lack of synergism may be due to incomplete digestion of
      the cell wall by endochitinase, so that the effect of Bayleton at the cell
      membrane is not enhanced.

PMID- 11341312
TI  - Enhanced degradation of naphthalene by immobilization of Pseudomonas sp. strain
      NGK1 in polyurethane foam.
AB  - A Pseudomonas sp. strain NGKI (NCIM 5120) capable of degrading naphthalene was
      immobilized in polyurethane foam. The naphthalene-degrading activity of the
      freely suspended cells was compared with that of immobilized cells in batches in
      shaken culture and in a continuous culture system in a packed-bed reactor.
      Increasing concentrations of naphthalene were better tolerated and more quickly
      degraded by immobilized cell cultures than by free cells. An initial naphthalene
      concentration of 25 mM was completely degraded by freely suspended cells (4 x
      10(10) cfu ml(-1)) and polyurethane-foam-immobilized cells (0.8-1 x 10(12) cfu g(
      1) foam cubes) after 4 days and 2 days of incubation, respectively. Free cells
      degraded a maximum of 30 mM naphthalene after 4 days of incubation with 50 mM
      naphthalene, and no further degradation was observed even after 15 days of
      incubation, whereas foam-immobilized cells brought about the complete degradation
      of 50 mM initial naphthalene after 6 days of incubation. Furthermore, with 25 mM
      naphthalene, the polyurethane-foam-immobilized cells were re-used 45 times over a
      period of 90 days without losing naphthalene-degrading activity. By contrast,
      with the same amount of naphthalene, alginate-, agar-, and polyacrylamide
      entrapped cells could be reused for 18, 12, and 23 times over a period of 44, 28,
      and 50 days, respectively. During continuous degradation in a packed-bed reactor,
      foam-immobilized cells degraded 80 mM naphthalene at a rate of 150 ml(-1) h(-1).
      With the same flow rate and 40 mM naphthalene, this system operated efficiently
      and continuously for about 120 days, whereas the packed-bed reactor with alginate
      , agar-, and polyacrylamide-entrapped cells could be operated only for 45, 40,
      and 60 days respectively. Thus, more efficient degradation of naphthalene could
      be achieved by immobilizing cells of Pseudomonas sp. strain NGK1 in polyurethane
      foam, rather than in the other matrices tested.

PMID- 11341313
TI  - Reactivity of Trametes laccases with fatty and resin acids.
AB  - Lipophilic extractives commonly referred to as wood pitch or wood resin can have
      a negative impact on paper machine runnability and product quality. The
      lipophilic extractives are composed mainly of fatty acids, resin acids, sterols,
      steryl esters and triglycerides. In this work, the suitability of laccases for
      the modification of fatty and resin acids was studied, using two model fractions.
      In the treatments, resin and fatty acid dispersions were treated with two
      different laccases, i.e. laccases from Trametes hirsuta and T. villosa. Different
      chromatographic methods were used to elucidate the effects of laccase treatments
      on the chemistry of the fatty and resin acids. Both laccases were able to modify
      the fatty and resin acids to some extent. In the case of fatty acids, a decrease
      in the amount of linoleic, oleic and pinolenic acids was observed, whereas the
      modification of resin acids resulted in a reduced amount of conjugated resin
      acids.

PMID- 11341314
TI  - Biotransformations catalyzed by cloned p-cymene monooxygenase from Pseudomonas
      putida F1.
AB  - p-Cymene monooxygenase (CMO) from Pseudomonas putida F1 consists of a hydroxylase
      (CymA1) and a reductase component (CymA2) which initiate pcymene (p
      isopropyltoluene) catabolism by oxidation of the methyl group to p
      isopropylbenzyl alcohol (p-cumic alcohol). To study the possible diverse range of
      substrates catalyzed by CMO, the cymA1A2 genes were cloned in an Escherichia coli
      pT7-5 expression system and the cells were used in transformation experiments.
      The tested substrates include different substituents on the aromatic ring at the
      2 (ortho), 3 (meta) or 4 (para) position relative to the methyl moiety. As a
      result, a distinct preference was observed for substrates containing at least an
      alkyl or heteroatom substituent at the para-position of toluene. The conversion
      rate of 4-chlorotoluene or 4-methylthiotoluene to the corresponding benzyl
      alcohol was found to be as good as the canonical substrate, p-cymene. But 3
      chlorotoluene, 4-fluorotoluene and 4-nitrotoluene were relatively poor
      substrates. CMO is also capable of producing styrene oxide from styrene. However,
      the oxidation of 4-chlorostyrene to 4-chlorostyrene oxide was by far the fastest
      among the substrates used in this study. The various biotransformation products
      were identified by a combined solid phase microextraction/gas chromatographic
      mass spectrometric analytical technique.

PMID- 11341315
TI  - Proteome and transcriptome based analysis of Bacillus subtilis cells
      overproducing an insoluble heterologous protein.
AB  - Bacillus subtilis and related Bacillus species are frequently used as hosts for
      the industrial production of recombinant proteins. In this study the cellular
      response of B. subtilis to the overproduction of an insoluble heterologous
      protein was investigated. For this purpose PorA, an outer membrane protein from
      Neisseria meningitidis, which accumulates after overexpression in the cytoplasm
      of B. subtilis mainly in the form of inclusion bodies, was used. The molecular
      response to overexpression of porA has been analysed at the transcriptional level
      using the DNA macro array technique and at the translational level by two
      dimensional polyacrylamide gel electrophoresis. It was found that the expression
      of the heat shock genes of class I (dnaK, groEL and grpE) and class III (clpP and
      clpC) are increased under overproducing conditions. Furthermore, the protein
      levels of the two ribosomal proteins RpsB and RplJ are increased in the PorA
      overproducing cells. The transcriptome analysis indicated that mRNA levels of
      genes encoding pyrimidine and purine synthesis enzymes but also from ribosomal
      protein genes have elevated levels under overproducing conditions. Finally, the
      association of the protease ClpP and its ATPase subunits ClpC and ClpX with the
      PorA inclusion bodies was demonstrated by means of the immunogold labelling
      technique.

PMID- 11341316
TI  - HO gene polymorphism in Saccharomyces industrial yeasts and application of novel
      HO genes to convert homothallism to heterothallism in combination with the mating
      type detection cassette.
AB  - Southern blot analysis of industrial yeasts showed that all top-fermenting
      yeasts, distiller's yeasts and a proportion of wine yeasts tested in the present
      study produced a hybridization signal (approximately 7 kb), corresponding to a
      Saccharomyces cerevisiae-type HO gene (Sc-HO). It also showed that bottom
      fermenting yeasts gave rise to 7-kb and 4-kb hybridization signals, corresponding
      to the Sc-HO gene and the lager yeast HO gene (Lg-HO), respectively. Two wine
      yeasts produced a 4-kb hybridization signal, corresponding to Lg-HO; and one wine
      yeast produced 2.5-kb and 1.5-kb hybridization bands, corresponding to a S.
      uvarum-type HO gene (Uv-HO). Partial nucleotide sequences of HO genes amplified
      from these wine yeasts perfectly matched those of Lg-HO and Uv-HO, respectively.
      HO disruption vectors were constructed by inserting a dominant selective marker
      PGK1p-neo and the mating-type detection cassette MFalpha1p-PHO5 within the Lg-HO
      or Uv-HO gene. From transformants carrying a single-disrupted ho gene, mating
      competent progenies were easily obtained through meiosis. Moreover, mating
      competent derivatives appearing at very low frequency could be obtained from a
      double-disrupted ho transformant without meiosis (even from a wine yeast lacking
      sporulation ability), because the sensitive phosphatase-staining method allowed
      detection of the Pho+ mating-competent derivatives from confluent colonies by the
      random spore method. Our study describes a rapid and convenient method for
      isolating mating-competent clones from industrial yeasts.

PMID- 11341317
TI  - Citrate, a possible precursor of astaxanthin in Phaffia rhodozyma: influence of
      varying levels of ammonium, phosphate and citrate in a chemically defined medium.
AB  - The influence of ammonium, phosphate and citrate on astaxanthin production by the
      yeast Phaffia rhodozyma was investigated. The astaxanthin content in cells and
      the final astaxanthin concentration increased upon reduction of ammonium from 61
      mM to 12.9 mM (from 140 microg/g to 230 microg/g and 1.2 microg/ml to 2.3
      microg/ml, respectively). Similarly, both the astaxanthin content and astaxanthin
      concentration increased by reducing phosphate from 4.8 mM to 0.65 mM (160
      microg/g to 215 microg/g and 1.7 microg/ml to 2.4 microg/ml, respectively). Low
      concentrations of ammonium or phosphate also increased the fatty acid content in
      cells. By analogy with lipid synthesis in other oleaginous yeasts, an examination
      of the data for varying nitrogen and phosphate levels suggested that citrate
      could be the source of carbon for fatty acids and carotenoid synthesis.
      Supporting this possibility was the fact that supplementation of citrate in the
      medium at levels of 28 mM or higher notably increased the final pigment
      concentration and pigment content in cells. Increased carotenoid synthesis at low
      ammonium or phosphate levels, and stimulation by citrate were both paralleled by
      decreased protein synthesis. This suggested that restriction of protein synthesis
      could play an important role in carotenoid synthesis by P. rhodozyma.

PMID- 11341318
TI  - Isolation and characterization of two aerobic bacterial strains that completely
      degrade ethyl tert-butyl ether (ETBE).
AB  - Two bacterial strains, E1 and E2, isolated from gasoline-polluted soil completely
      degraded ethyl tert-butyl ether (ETBE), as the sole source of carbon and energy,
      at specific rates of about 80 mg g(-1) and 58 mg g(-1) of cell protein day(-1),
      respectively. On the basis of morphological and phenotypic characteristics,
      strain E1 was tentatively identified as Comamonas testosteroni and strain E2 as
      belonging to Centre for Disease Control group A-5. The inhibitory effect of
      metyrapone on the degradative ability of both strains was the first evidence
      indicating the involvement of a soluble cytochrome P-450 in the cleavage of the
      ETBE ether bond. This observation was confirmed by spectrophotometric analysis of
      reduced cell extracts that gave, in the presence of carbon monoxide, a major
      absorbance peak at about 450 nm. Both strains were also able to degrade, as the
      sole source of carbon and energy, ETBE's major metabolic intermediates (tert
      butyl alcohol and tert-butyl formate) and other gasoline oxygenates (methyl tert
      butyl ether and tert-amyl methyl ether). The degradation rates varied
      considerably, with both strains exhibiting a preferential activity for ETBE's
      metabolic intermediates.

PMID- 11341319
TI  - Screening, overexpression and characterization of an N-acylamino acid racemase
      from Amycolatopsis orientalis subsp. lurida.
AB  - Thirty-one different actinomycete strains were used in a genetic screening using
      PCR and Southern hybridization methods to detect N-acetylamino acid racemases
      (AAR) in order to obtain enzymes with different properties. Cloning and
      sequencing of a 2.5 kb EcoRI DNA fragment from Amycolatopsis orientalis subsp.
      lurida revealed the coding gene of an N-acetylamino acid racemase, which had
      identities to the aar gene of Amycolatopsis sp. TS-1-60 [Tokuyama and Hatano
      (1995) Appl Microbiol Biotechnol 42:884-889] of 86% at the level of DNA, and 90%
      at the level of amino acids. The heterologous overexpression in Escherichia coli
      resulted in a specific activity of about 0.2 U/mg of this racemase. A two-step
      purification with heat treatment followed by anion-exchange chromatography led to
      almost homogeneous enzyme. The optimum pH of the enzyme was 8.0 and it was stable
      at 50 degrees C for 30 min. The relative molecular mass of the native enzyme and
      the subunit was calculated to be 300 kDa and 40 kDa by gel filtration and SDS
      PAGE, respectively. The isoelectric point (pI) of the AAR was 4.4. It catalyzed
      the racemization of optically active N-acetylamino acids such as N-acetyl-L- or 
      D-methionine and N-acetyl-L-phenylalanine. Further characterization of the
      racemase demonstrated a requirement for divalent metal ions (Co2+, Mn2+, Mg2+)
      for activity and inhibition by EDTA and p-hydroxymercuribenzoic acid. AAR is
      sensitive to substrate inhibition at concentrations exceeding 200 mM.

PMID- 11341320
TI  - Automatic method for evaluating the activity of sourdough strains based on gas
      pressure measurements.
AB  - A new method is proposed for the evaluation of the activity of sourdough strains,
      based on gas pressure measurements in closed air-tight reactors. Gas pressure and
      pH were monitored on-line during the cultivation of commercial yeasts and
      heterofermentative lactic acid bacteria on a semi-synthetic medium with glucose
      as the major carbon source. Relative gas pressure evolution was compared both to
      glucose consumption and to acidification and growth. It became obvious that gas
      pressure evolution is related to glucose consumption kinetics. For each strain, a
      correlation was made between maximum gas pressure variation and amount of glucose
      consumed. The mass balance of CO2 in both liquid and gas phase demonstrated that
      around 90% of CO2 was recovered. Concerning biomass production, a linear
      relationship was found between log colony-forming units/ml and log pressure for
      both yeasts and bacteria during the exponential phase; and for yeasts, relative
      gas pressure evolution also followed optical density variation.

PMID- 11341321
TI  - Biodegradation of tert-butyl alcohol and related xenobiotics by a methylotrophic
      bacterial isolate.
AB  - A new aerobic bacterial strain, CIP 1-2052, isolated from an activated sludge
      sample, was able to use tert-butyl alcohol (TBA), a product of methyl tert-butyl
      ether (MTBE) and ethyl tert-butyl ether (ETBE) degradation, as its sole carbon
      and energy source. Cobalt ions stimulated TBA mineralization. The maximum growth
      and TBA degradation rates were 0.032 +/- 0.004 h(-1) and 35.8 +/- 8.5 mg TBA x g(
      1) (cell dry mass) per h, respectively. The growth yield on TBA was 0.54 +/- 0.02
      g x g(-1). Strain CIP 1-2052 exhibited a particular substrate specificity towards
      alcohols. It degraded tertiary alcohols, TBA and tert-amyl alcohol (TAA), but
      neither their primary and secondary alcohol homologues, nor ethanol. However, one
      carbon compounds, namely methanol and formate, were degraded by strain CIP 1
      2052, showing the methylotrophic nature of this isolate. The properties of this
      new strain suggest that it could be used for bioremediation of contaminated
      aquifers.

PMID- 11341322
TI  - Long-term repeated biodesulfurization by immobilized Rhodococcus erythropolis KA2
      5-1 cells.
AB  - In this study, biodesulfurization (BDS) was carried out using immobilized
      Rhodococcus erythropolis KA2-5-1 in n-tetradecane containing dibenzothiophene
      (DBT) as a model oil (n-tetradecane/immobilized cell biphasic system). The cells
      were immobilized by entrapping them with calcium alginate, agar, photo
      crosslinkable resin prepolymers (ENT-4000 and ENTP-4000), and urethane
      prepolymers (PU-3 and PU-6); and it was found that ENT-4000-immobilized cells had
      the highest DBT desulfurization activity in the model oil system without leakage
      of cells from the support. Furthermore, ENT4000-immobilized cells could catalyze
      BDS repeatedly in this system for more than 900 h with reactivation; and recovery
      of both the biocatalyst and the desulfurized model oil was easy. This study would
      give a solution to the problems in BDS, such as the troublesome process of
      recovering desulfurized oil and the short life of BDS biocatalysts.

PMID- 11341323
TI  - Concurrent sorption of Ni2+ and Cu2+ by Chlorella vulgaris from a binary metal
      solution.
AB  - Kinetics and capacity of Ni2+ and Cu2+ sorption by Chlorella vulgaris were
      studied using single and binary metal solutions at various concentrations of
      these metal ions. The second-order rate law best described the kinetics of metal
      sorption from both single and binary metal systems. C. vulgaris preferentially
      sorbed Cu2+ over Ni2+ in the binary system. In comparison to the single metal
      system, the amounts of Ni2+ and Cu2+ sorbed at equilibrium (qe) were respectively
      73% and 25%, and the initial rate of sorption (h) was ca. 50% in the case of the
      binary metal system. The test metals inhibited sorption of each other, thereby
      indicating competition between Ni2+ and Cu2+ for sorption onto non-specific
      binding sites. The present study showed that C. vulgaris has specific as well as
      non-specific sites for the binding of Ni2+ and Cu2+. Participation of these sites
      for sorption depended on the ratio of Ni2+ and CU2+ in solution. The maximum
      metal sorption capacity of C. vulgaris was 6.75 mmol g(-1) from the binary metal
      solution at the tested biomass concentration (100 mg dry weight l(-1)). Total
      metal sorption was enhanced with increasing total concentration of both the
      metals up to 1.6 mM, beyond which a decrease occurred. Two-dimensional contour
      plots were successfully used for the first time for the evaluation of metal
      sorption potential.

PMID- 11341324
TI  - Inaccuracies inherent in dual-energy X-ray absorptiometry in vivo bone mineral
      density can seriously mislead diagnostic/prognostic interpretations of patient
      specific bone fragility.

PMID- 11341325
TI  - Renal phosphate wasting in fibrous dysplasia of bone is part of a generalized
      renal tubular dysfunction similar to that seen in tumor-induced osteomalacia.
AB  - Fibrous dysplasia (FD) of bone is characterized by focal replacement of normal
      bone and marrow with abnormal bone and fibrous tissue. It arises from postzygotic
      activating mutations of the GNAS1 gene. Hypophosphatemia due to renal phosphate
      wasting has been reported in association with FD as a part of the McCune-Albright
      Syndrome (MAS), which is characterized by FD, skin hyperpigmentation, and
      precocious puberty. To date, the prevalence and mechanism of phosphate wasting
      has not been well studied. We evaluated 42 patients with FD/MAS. Serum and urine
      samples were tested for indices of mineral metabolism, amino acid handling, and
      markers of bone metabolism. Twenty (48%) patients had some degree of renal
      phosphate wasting. Nephrogenous cyclic adenosine monophosphate (cAMP) was normal
      in FD patients, suggesting that the underlying cause of phosphate wasting is not
      the presence of activating GNAS1 mutations in the kidney. In addition, there was
      evidence of a more generalized renal tubulopathy as represented by the presence
      of abnormal vitamin D metabolism, proteinuria in 36 (86%) patients, and
      aminoaciduria in 39 (94%) patients. Renal phosphate wasting significantly
      correlated with the degree of bone involvement, as assessed by serum and urine
      markers of bone metabolism, suggesting that a circulating factor produced by FD
      bone and impacting on the kidney may be the mechanism. These data show that
      phosphaturia as part of a generalized renal tubulopathy represents the most
      common extraskeletal manifestation of FD and that the observed tubulopathy is
      similar to that seen in tumor-induced osteomalacia (TIO).

PMID- 11341326
TI  - ADAM8: a novel osteoclast stimulating factor.
AB  - We used polymerase chain reaction (PCR)-selective complementary DNA (cDNA)
      subtraction hybridization with an immortalized murine osteoclast (OCL) precursor
      cell line to identify genes that are highly expressed in OCLs compared with OCL
      precursors and which may be involved in the OCL differentiation process. ADAM8
      was one of the 50 genes identified. ADAM (a disintegrin and metalloproteinase)
      peptides are membrane-bound proteins that can act as cell-to-cell and cell-to
      matrix adhesion molecules, degrade the extracellular matrix, and play a role in
      tissue morphogenesis. Addition of antisense (AS) S-oligonucleotides for ADAM8 (1
      10 nM) to mouse bone marrow cultures treated with 10(-9) M 1,25-dihydroxyvitamin
      D3 [1,25-(OH)2D3] significantly inhibited OCL formation compared with treatment
      with the control S-oligonucleotide. Furthermore, conditioned media from 293 cells
      transiently transfected with a secretable form of the ADAM8 cDNA increased OCL
      formation in a dose-dependent manner. In addition, treatment of OCLs with soluble
      ADAM8 conditioned media significantly increased pit formation per dentin slice
      compared with control OCLs. Time course studies indicated that ADAM8 increased
      OCL formation only when it was present during days 4-7 of the 7-day culture
      period. Structural analysis, using truncated constructs of ADAM8, showed that the
      cysteine-rich/disintegrin domain was responsible for its OCL stimulatory
      activity. Western blot analysis confirmed that the soluble form of ADAM8 is
      present in normal marrow cultures. These data suggest that ADAM8 plays an
      important role in OCL formation and acts primarily at the later stages of OCL
      differentiation.

PMID- 11341327
TI  - The hormonal milieu in early stages of bone cell differentiation modifies the
      subsequent sex-specific responsiveness of the developing bone to gonadal
      steroids.
AB  - We have established previously that rat bone tissue, as well as rat and human
      derived bone cells in culture, show a sex-specific response to gonadal steroids
      in stimulation of the specific activity of the BB isozyme of creatine kinase (CK)
      and DNA synthesis. This response could be modified by manipulation of the
      endocrine environment during early stages in rat development. To further examine
      the influence of changing hormonal steroid milieu and vitamin D status on the
      action of gonadal steroids in developing bone tissue, we used two models of
      ectopic bone formation: demineralized tooth matrix (DTM) implanted under the
      skin, and femoral bone marrow (BM) transplanted under the kidney capsule of a
      syngeneic recipient mouse. The response to gonadal steroids in ossicles developed
      from implanted DTM depended on the recipient's gender; injection of estradiol
      17beta (E2; 5 microg) into young female mice 21 days after DTM implantation
      increased, 24 h later, CK activity in the newly formed ossicles by approximately
      60%, whereas injection of dihydrotestosterone (DHT; 50 microg) had no effect on
      CK activity. In contrast, in male mice, DHT but not E2 increased CK activity in
      the ossicles by approximately 50%. This sex-specific response was abolished in
      gonadectomized mice resulting in a similar response of the ossicles to both E2
      and DHT. When DTM was implanted into vitamin D- deficient female mice, there was
      a lower basal CK activity and a significantly diminished response to E2 in the
      newly formed bone tissues. When BM, which contains mesenchymal and stromal cells
      and committed osteoprogenitor cells, was transplanted into 6-week-old intact or
      gonadectomized female or male mice, the response of the newly formed bone
      ossicles, 21 days after transplantation, to E2 or to DHT was according to the
      gender of the donor. Bone formed from BM obtained from female mice responded to
      E2 only and those formed from male BM responded to DHT only. Ossicles developed
      from BM obtained from gonadectomized mice showed lack of response to either
      gonadal steroid. Furthermore, only approximately 25% of the BM transplants
      obtained from castrated (CAST) male donors developed into ossicles. Ossicles
      formed from BM obtained from vitamin D-deficient female donors showed lack of
      response to gonadal steroids. These findings suggest that the manipulation of the
      hormonal milieu in early stages of the differentiation sequence of bone cells
      modifies the subsequent selective responsiveness of the developing bone tissue to
      gonadal steroids.

PMID- 11341328
TI  - Role of N-cadherin and protein kinase C in osteoblast gene activation induced by
      the S252W fibroblast growth factor receptor 2 mutation in Apert craniosynostosis.
AB  - Apert (Ap) syndrome is characterized by premature cranial suture ossification
      caused by fibroblast growth factor receptor 2 (FGFR-2) mutations. We studied the
      role of cadherins and signaling events in the phenotypic alterations induced by
      the Ap FGFR-2 S252W mutation in mutant immortalized fetal human calvaria
      osteoblasts. The FGFR-2 mutation caused increased expression of the osteoblast
      markers alkaline phosphatase (ALP), type 1 collagen (COLIA1), and osteocalcin
      (OC) in long-term culture. The mutation also increased cell-cell aggregation,
      which was suppressed by specific neutralizing anti-N- and anti-E-cadherin
      antibodies. Mutant osteoblasts showed increased N- and E-cadherin, but not N-cell
      adhesion molecule (N-CAM) messenger RNA (mRNA) and protein levels. This was
      confirmed in vivo by the abundant immunoreactive N- and E-cadherins in
      preosteoblasts in the Ap suture whereas N-CAM and alpha- and beta-catenins were
      unaffected. Neutralizing anti-N-cadherin antibody or N-cadherin antisense (AS)
      oligonucleotides but not anti-E-cadherin antibody or AS reduced ALP activity as
      well as ALP, COLIA1, and OC mRNA overexpression in mutant osteoblasts. Analysis
      of signal transduction revealed increased phospholipase Cgamma (PLCgamma) and
      protein kinase Calpha (PKCalpha) phosphorylation and increased PKC activity in
      mutant cells in basal conditions. Inhibition of PKC by calphostin C or the
      PKCalpha-specific inhibitor Go6976 suppressed the increased N-cadherin mRNA and
      protein levels as well as the overexpression of ALP, COLIA1, and OC mRNA in
      mutant cells. Thus, N-cadherin plays a role in the activation of osteoblast
      differentiation marker genes in mutant osteoblasts and PKCalpha signaling appears
      to be involved in the increased N-cadherin and osteoblast gene expression induced
      by the S252W FGFR-2 mutation in human osteoblasts.

PMID- 11341329
TI  - Expression of a P2X7 receptor by a subpopulation of human osteoblasts.
AB  - There is now conclusive evidence that extracellular nucleotides acting via cell
      surface P2 receptors are important local modulators of bone cell function.
      Multiple subtypes of P2 receptors have been localized to bone, where their
      activation modulates multiple processes including osteoblast proliferation,
      osteoblast-mediated bone formation, and osteoclast formation and resorptive
      capacity. Locally released nucleotides also have been shown to sensitize
      surrounding cells to the action of systemic factors such as parathyroid hormone
      (PTH). In nonskeletal tissue recent attention has focused on one particular P2
      receptor, the P2X7 receptor (previously termed P2Z), and its ability to form
      nonselective aqueous pores in the plasma membrane on prolonged stimulation.
      Expression of this receptor originally was thought to be restricted to cells of
      hemopoietic origin, in which it has been implicated in cell fusion, apoptosis,
      and release of proinflammatory cytokines. However, recent reports have indicated
      expression of this receptor in cells of stromal origin. In this study, we
      investigated the expression of the P2X7 receptor in two human osteosarcoma cell
      lines, as well as several populations of primary human bone-derived cells (HBDCs)
      at the levels of messenger RNA (mRNA) and protein. We found that there is a
      subpopulation of osteoblasts that expresses the P2X7 receptor and that these
      receptors are functional as assessed by monitoring ethidium bromide uptake
      following pore formation. Inhibition of delayed lactate dehydrogenase (LDH)
      release in response to the specific agonist 2',3'-(4-benzoyl)-benzoyl-adenosine
      triphosphate (BzATP) by the nonspecific P2X receptor antagonist PPADS confirmed a
      receptor-mediated event. After treatment with BzATP SaOS-2 cells exhibited
      dramatic morphological changes consistent with those observed after P2X7-mediated
      apoptosis in hemopoietic cells. Dual staining with terminal deoxynucleotidyl
      transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL)
      and a P2X7-specific monoclonal antibody confirmed the induction of apoptosis in
      osteoblasts expressing the P2X7 receptor. These data show for the first time the
      expression of functional P2X7 receptors in a subpopulation of osteoblasts,
      activation of which can result in ATP-mediated apoptosis.

PMID- 11341330
TI  - Bone formation by transplanted human osteoblasts cultured within collagen sponge
      with dexamethasone in vitro.
AB  - To apply osteoblasts to bone reconstruction, we proved that transplanted
      osteoblasts possessed the differentiated osteoblastic function and formed
      bonelike tissue in vivo after transplantation. First, we confirmed that
      dexamethasone (Dex) promoted the expression of osteoblastic phenotype in human
      osteoblast culture using reverse-transcription-polymerase chain reaction (RT
      PCR). These osteoblasts were cultured for 10 days within collagen sponge, which
      consists of denatured type I collagen, in the presence or absence of 10(-7) M
      Dex. The osteoblasts along with collagen sponge were transplanted into the
      trapezius muscles of 8-week-old severe combined immunodeficiency (SCID) mice, and
      the transplants were harvested at 2, 4, 6, and 8 weeks. At 2 weeks, Dex-treated
      osteoblasts formed bonelike tissue, the quantity of which increased in a time
      dependent manner to 8 weeks. This bonelike tissue was composed of mineralized
      collagen matrix newly synthesized by the transplanted osteoblasts. This
      mineralized matrix was separated from the osteoblasts by nonmineralized
      matrixlike osteoid. Furthermore, many osteocytic cells were observed in this
      mineralized matrix. A high expression of alkaline phosphatase (ALPase) and
      osteocalcin was detected in the transplanted cells surrounding the bonelike
      tissue. In situ hybridization for human-specific alu sequence indicated that
      newly formed bone was of donor origin. The transplants of nontreated cells failed
      to form bonelike tissue. The transplants of collagen sponge alone formed no
      bonelike tissue. These studies indicate that Dex-treated human osteoblasts
      possess the differentiated osteoblastic function and are able to form bone tissue
      in vivo. These new findings are of use in facilitating the application of
      osteoblasts to bone reconstruction.

PMID- 11341331
TI  - Variations in site and levels of expression of chondrocyte nucleotide
      pyrophosphohydrolase with aging.
AB  - The aim of this study was to identify changes in cartilage intermediate layer
      protein/nucleotide pyrophosphohydrolase (CILP/NTPPH) expression in articular
      cartilage during aging. Adult (3-4 years old) and young (7-10 days old) porcine
      articular hyaline cartilage and fibrocartilage were studied by Northern blot
      analysis, in situ hybridization, and immunohistochemistry using a complementary
      DNA (cDNA) probe encoding porcine CILP/NTPPH and antibody to a synthetic peptide
      corresponding to a CILP/NTPPH sequence. Northern blot analysis of chondrocytes
      showed lower expression of CILP/NTPPH messenger RNA (mRNA) in young cartilage
      than in adult cartilage. In adult cartilage, extracellular matrix from the
      surface to the middeep zone was immunoreactive for CILP/NTPPH, especially in the
      pericellular matrix surrounding the middeep zone chondrocytes. In young
      cartilage, chondrocytes were moderately immunoreactive for CILP/NTPPH throughout
      all zones except the calcified zone. The matrix of young cartilage was negative
      except in the superficial zone. In young cartilage, CILP/NTPPH mRNA expression
      was undetectable. In adult cartilage, chondrocytes showed strong mRNA expression
      for CILP/NTPPH throughout middeep zones. Protein and mRNA signals were not
      detectable below the tidemark. CILP/NTPPH secretion into matrix around
      chondrocytes increases with aging. In this extracellular site it may generate
      inorganic pyrophosphate and contribute to age-related calcium pyrophosphate
      dihydrate crystal deposition disease.

PMID- 11341332
TI  - Colocalization of noggin and bone morphogenetic protein-4 during fracture
      healing.
AB  - The regulation of callus formation during fracture repair involves the coordinate
      expression of growth factors and their receptors. This article describes the
      temporal and spatial expression of noggin gene, an antagonist to bone
      morphogenetic protein (BMP), during the fracture repair process. Noggin
      expression was examined by means of Northern blotting and in situ hybridization
      and compared with the expression pattern of BMP-4 in a model of fracture repair
      in adult mice. Expression levels of noggin messenger RNA (mRNA) were enhanced in
      the early phase of fracture callus formation. The localization of the noggin mRNA
      was similar to that of BMP-4 mRNA. Distinct noggin mRNA signals were located
      predominantly in cells lining the periosteum and the cortical endosteum near the
      fracture site at 2 days after fracture. At 5, 10, and 21 days after fracture,
      noggin mRNA was detected in the chondrocytes and osteoblasts in the newly formed
      callus. The pattern of localization was indistinguishable from that of BMP-4.
      These results suggest that the noggin/BMP-4 balance could be an important factor
      in the regulation of callus formation during fracture healing.

PMID- 11341333
TI  - Differential expression patterns of Runx2 isoforms in cranial suture
      morphogenesis.
AB  - Runx2 (previously known as Cbfal/Pebp2alphaA/AML3), a key transcription factor in
      osteoblast differentiation, has at least two different isoforms using alternative
      promoters, which suggests that the isoforms might be expressed differentially.
      Haploinsufficiency of the Runx2 gene is associated with cleidocranial dysplasia
      (CCD), the main phenotype of which is inadequate development of calvaria. In
      spite of the biological relevance, Runx2 gene expression patterns in developing
      calvaria has not been explored previously, and toward this aim we developed three
      probes: pRunx2, which comprises the common coding sequence of Runx2 and
      hybridizes with all isoforms; pPebp2alphaA, which specifically hybridizes with
      the isoform transcribed with the proximal promoter; and pOsf2, which hybridizes
      with the isoform transcribed with the distal promoter. These probes were
      hybridized with tissue sections of mouse calvaria taken at various time points in
      development. Runx2 expression was localized to the critical area of cranial
      suture closure, being found in parietal bones, osteogenic fronts, and sutural
      mesenchyme. Pebp2alphaA and Osf2 showed tissue-specific expression patterns. The
      sites of Pebp2alphaA expression were almost identical to that of pRunx2
      hybridization but expression was most intense in the sutural mesenchyme, where
      undifferentiated mesenchymal cells reside. The Osf2 isoform was strongly
      expressed in the osteogenic fronts, as well as in developing parietal bones,
      where osteopontin (OP) and osteocalcin (OC) also were expressed. However, in
      contrast to Pebp2alphaA, Osf2 expression did not occur in sutural mesenchyme.
      Pebp2alphaA also was expressed prominently in primordial cartilage that is found
      under the sutural mesenchyme and is not destined to be mineralized. Thus, Osf2
      isoforms contribute to events later in osteoblast differentiation whereas the
      Pebp2alphaA isoform participates in a wide variety of cellular activities ranging
      from early stages of osteoblast differentiation to the final differentiation of
      osteoblasts.

PMID- 11341334
TI  - Infrared microscopic imaging of bone: spatial distribution of CO3(2-).
AB  - This article describes a novel technology for quantitative determination of the
      spatial distribution of CO3(2-) substitution in bone mineral using infrared (IR)
      imaging at approximately 6 microm spatial resolution. This novel technology
      consists of an IR array detector of 64 x 64 elements mapped to a 400 microm x 400
      microm spot at the focal plane of an IR microscope. During each scan, a complete
      IR spectrum is acquired from each element in the array. The variation of any IR
      parameter across the array may be mapped. In the current study, a linear
      relationship was observed between the band area or the peak height ratio of the
      CO3(2-) v3 contour at 1415 cm(-1) to the PO4(3-) v1,v3 contour in a series of
      synthetic carbonated apatites. The correlation coefficient between the
      spectroscopically and analytically determined ratios (R2 = 0.989) attests to the
      practical utility of this IR area ratio for determination of bone CO3(2-) levels.
      The relationship forms the basis for the determination of CO3(2-) in tissue
      sections using IR imaging. In four images of trabecular bone the average CO3(2-)
      levels were 5.95 wt% (2298 data points), 6.67% (2040 data points), 6.66% (1176
      data points), and 6.73% (2256 data points) with an overall average of 6.38+/
      0.14% (7770 data points). The highest levels of CO3(2-) were found at the edge of
      the trabeculae and immediately adjacent to the Haversian canal. Examination of
      parameters derived from the phosphate v1,v3 contour of the synthetic apatites
      revealed that the crystallinity/perfection of the hydroxyapatite (HA) crystals
      was diminished as CO3(2-) levels increased. The methodology described will permit
      evaluation of the spatial distribution of CO3(2-) levels in diseased and normal
      mineralized tissues.

PMID- 11341335
TI  - Classification of osteoporosis based on bone mineral densities.
AB  - In this article we examine the role of bone mineral density (BMD) in the
      diagnosis of osteoporosis. Using information from 7671 women in the Study of
      Osteoporotic Fractures (SOF) with BMD measurements at the proximal femur, lumbar
      spine, forearm, and calcaneus, we examine three models with differing criteria
      for the diagnosis of osteoporosis. Model 1 is based on the World Health
      Organization (WHO) criteria using a T score of -2.5 relative to the
      manufacturers' young normative data aged 20-29 years, with modifications using
      information from the Third National Health and Nutrition Examination Survey
      (NHANES). Model 2 uses a T score of -1 relative to women aged 65 years at the
      baseline of the SOF population. Model 3 classifies women as osteoporotic if their
      estimated osteoporotic fracture risk (spine and/or hip) based on age and BMD is
      above 14.6%. We compare the agreement in osteoporosis classification according to
      the different BMD measurements for the three models. We also consider whether
      reporting additional BMD parameters at the femur or forearm improves risk
      assessment for osteoporotic fractures. We observe that using the WHO criteria
      with the manufacturers' normative data results in very inconsistent diagnoses.
      Only 25% of subjects are consistently diagnosed by all of the eight BMD
      variables. Such inconsistency is reduced by using a common elderly normative
      population as in model 2, in which case 50% of the subjects are consistently
      diagnosed as osteoporotic by all of the eight diagnostic methods. Risk-based
      diagnostic criteria as in model 3 improve consistency substantially to 68%.
      Combining the results of BMD assessments at more than one region of interest
      (ROI) from a single scan significantly increases prediction of hip and/or spine
      fracture risk and elevates the relative risk with increasing number of low BMD
      subregions. We conclude that standardization of normative data, perhaps
      referenced to an older population, may be necessary when applying T scores as
      diagnostic criteria in patient management. A risk-based osteoporosis
      classification does not depend on the manufacturers' reference data and may be
      more consistent and efficient for patient diagnosis.

PMID- 11341336
TI  - A common promotor variant in the cytochrome P450c17alpha (CYP17) gene is
      associated with bioavailability testosterone levels and bone size in men.
AB  - Cytochrome P450c17alpha (CYP17) encodes an enzyme with 17a-hydroxylase and 17,20
      lyase activities, which is essential for the normal production of adrenal and
      gonadal androgens. Because androgens have powerful effects on bone growth and
      metabolism, we determined whether a single base pair (bp) substitution (T-->C) in
      the promoter region (-34 bp) of CYP17 is associated with sex hormone levels,
      stature, and femoral mass and size in 333 white men aged 51-84 years (mean +/-
      SD; 66+/-7 years). Femoral neck bone mineral content (BMC), cross-sectional area
      (CSA), and bone mineral density (BMD) were measured using dual-energy X-ray
      absorptiometry (DXA). Genotype frequencies did not deviate from Hardy-Weinberg
      expectations. Serum bioavailable testosterone levels were 20% or 0.5 SDs higher
      in men with the C/C compared with the T/T genotype, whereas heterozygous men had
      intermediate hormone levels (p = 0.019). Men with the C/C genotype also were
      nearly 3 cm taller and had 0.6 SD greater femoral neck CSA than men with the T/T
      genotype (p < or = 0.01 for both). The association with CSA persisted after
      adjusting for age, height, and body weight. In contrast, CYP17 genotype was not
      associated with femoral neck BMC, areal BMD (g/cm2), or estimated volumetric BMD
      (g/cm3). These results suggest that allelic variation at the CYP17 locus may
      contribute to the genetic influence on stature and femoral size in men.

PMID- 11341337
TI  - Effects of loading frequency on mechanically induced bone formation.
AB  - The anabolic effect of mechanical loading on bone tissue is modulated by loading
      frequency. The objective of this study was to characterize the new bone formation
      on the periosteal and endocortical surfaces of the ulnar diaphysis in adult,
      female rats in response to controlled dynamic loading and to examine the
      interactions between strain magnitude, loading frequency, and bone formation rate
      (BFR/BS) for frequencies ranging from 1 to 10 Hz. Cyclic, compressive loading was
      applied to the ulnas of 60 adult, female rats divided into 12 loading groups.
      Loading was applied for 360 cycles/day with peak loads ranging from 4.3 to 18N at
      frequencies of 1, 5, and 10 Hz. After 2 weeks of loading, bone formation on the
      periosteal and endocortical surfaces of the ulna was quantified using double
      label histomorphometry on transverse sections obtained at the middiaphysis.
      Periosteal bone formation increased in a dose-response manner with peak load at
      each of the three loading frequencies tested. Loading frequency significantly
      affected the x intercepts and slopes of the peak strain versus BFR/BS (p < 0.001)
      and peak strain versus mineralizing surface (MS/BS; p < 0.001) curves. Periosteal
      osteogenesis was best predicted by a mathematical model that assumed: (1) bone
      cells are activated by fluid shear stresses and (2) that stiffness of the bone
      cells and the extracellular matrix near the cells increases at higher loading
      frequencies because of viscoelasticity. Consequently, mechanotransduction appears
      to involve a complex interaction between extracellular fluid forces and cellular
      mechanics.

PMID- 11341338
TI  - Parathyroid hormone added to established hormone therapy: effects on vertebral
      fracture and maintenance of bone mass after parathyroid hormone withdrawal.
AB  - Our best pharmacologic agents for osteoporosis treatment prevent no more than 40
      60% of osteoporotic fractures in patients at highest risk. Thus, there is a need
      for agents that can further augment bone mass and reduce fracture risk more
      substantially. To this end, we investigated the utility of parathyroid hormone
      (PTH) in combination with established hormone-replacement therapy (HRT) in women
      with osteoporosis. Fifty-two women who had been on HRT for at least 2 years were
      enrolled in this trial in which 25 were assigned randomly to remain on HRT alone
      and 27 were assigned to remain on HRT and also receive daily subcutaneous PTH(1
      34) 400 U (25 microg) per day for 3 years. Bone mineral density (BMD)
      measurements at the spine, hip, and total body as well as biochemical
      determinations of bone turnover and calcium homeostasis were obtained every 6
      months. Lateral thoracic and lumbar spine X-rays were obtained at baseline and
      annually. Subjects also had measurements of bone density and biochemical indices
      of bone turnover 1 year after discontinuation of PTH, while HRT was continued. In
      the group receiving HRT alone, bone density and biochemical variables of bone
      turnover remained stable throughout the 3-year treatment trial and 1-year follow
      up. In the PTH + HRT group, biochemical variables of bone formation and
      resorption peaked at 6 months and subsequently remained elevated until 30 months
      at which time levels were indistinguishable from baseline. Subjects in the PTH +
      HRT group increased bone mass by 13.4+/-1.4% in the spine, 4.4+/-1.0% in the
      total hip, and 3.7+/-1.4% in the total body. Bone density measurements remained
      stable 1 year after discontinuation of PTH without any significant loss while
      women continued HRT. Biochemical variables did not change significantly after
      cessation of PTH through the 1-year follow-up period. PTH + HRT reduced the
      percent of women who had vertebral fractures from 37.5% to 8.3% (using a 15%
      height reduction criterion) and from 25% to 0% (using a 20% height reduction
      criterion) compared with women receiving HRT alone (p < 0.02 for both). We
      conclude that ongoing HRT maintains almost all of the PTH-induced bone mass
      increment for 1 year after discontinuation of PTH. Furthermore, PTH in
      combination with hormone therapy is an effective means of increasing bone mass
      throughout the skeleton and specifically reducing vertebral fracture occurrence
      by 75-100%, compared with HRT alone.

PMID- 11341339
TI  - Effect of long-term exposure to fluoride in drinking water on risks of bone
      fractures.
AB  - Findings on the risk of bone fractures associated with long-term fluoride
      exposure from drinking water have been contradictory. The purpose of this study
      was to determine the prevalence of bone fracture, including hip fracture, in six
      Chinese populations with water fluoride concentrations ranging from 0.25 to 7.97
      parts per million (ppm). A total of 8266 male and female subjects > or =50 years
      of age were enrolled. Parameters evaluated included fluoride exposure, prevalence
      of bone fractures, demographics, medical history, physical activity, cigarette
      smoking, and alcohol consumption. The results confirmed that drinking water was
      the only major source of fluoride exposure in the study populations. A U-shaped
      pattern was detected for the relationship between the prevalence of bone fracture
      and water fluoride level. The prevalence of overall bone fracture was lowest in
      the population of 1.00-1.06 ppm fluoride in drinking water, which was
      significantly lower (p < 0.05) than that of the groups exposed to water fluoride
      levels > or =4.32 and < or =0.34 ppm. The prevalence of hip fractures was highest
      in the group with the highest water fluoride (4.32-7.97 ppm). The value is
      significantly higher than the population with 1.00-1.06 ppm water fluoride, which
      had the lowest prevalence rate. It is concluded that long-term fluoride exposure
      from drinking water containing > or =4.32 ppm increases the risk of overall
      fractures as well as hip fractures. Water fluoride levels at 1.00-1.06 ppm
      decrease the risk of overall fractures relative to negligible fluoride in water;
      however, there does not appear to be similar protective benefits for the risk of
      hip fractures.

PMID- 11341340
TI  - Eating attitudes and habitual calcium intake in peripubertal girls are associated
      with initial bone mineral content and its change over 2 years.
AB  - This 2-year prospective study examined associations among bone mineral
      acquisition and physical, maturational, and lifestyle variables during the
      pubertal transition in healthy girls. Forty-five girls, initially 10.5+/-0.6
      years, participated. Body composition and bone mineral content (BMC) at the spine
      and total body (TB) were assessed at baseline and annually thereafter using dual
      energy X-ray absorptiometry (DXA). Nutrient intakes were assessed using 3-day
      diet records and a calcium food frequency questionnaire (FFQ), physical activity
      by questionnaire, sexual maturation using Tanner's stages of breast and pubic
      hair maturation, growth by height and weight, and eating attitudes using the
      children's Eating Attitudes Test (Children's EAT). Mean children's EAT subscale
      scores (dieting, oral control [OC], and bulimia) were stable over time. Median
      split of OC subscale scores was used to form high and low OC groups. Groups had
      similar body composition, dietary intake, activity, and Tanner stage at baseline
      and 2 years. Using height, weight, and Tanner breast stage as covariates, girls
      with low OC scores had greater TB BMC at baseline (1452+/-221 g vs. 1387+/-197 g;
      p = 0.030) and 2 years (2003+/-323 g vs. 1909+/-299 g; p = 0.049) and greater
      lumbar spine (LS) BMC at 2 years (45.2+/-8.8 g vs. 41.2+/-9.6 g; p = 0.042). In
      multiple regression analysis, OC score predicted baseline, 2 years, and 2-year
      change in TB and spinal BMC, contributing 0.9-7.6% to explained variance. Calcium
      intake predicted baseline, 2 years, and 2-year change in TB BMC, explaining 1.6
      5.3% of variance. We conclude that both OC and habitual calcium intake may
      influence bone mineral acquisition.

PMID- 11341341
TI  - Functional impact of human collagen alpha2(XI) gene polymorphism in pathogenesis
      of ossification of the posterior longitudinal ligament of the spine.
AB  - Ossification of the posterior longitudinal ligament (OPLL) of the spine is the
      leading cause of myelopathy in Japan. In earlier studies, we provided genetic
      linkage and allelic association evidence of distinct differences in the human
      collagen alpha2(XI) gene (COL11A2) that might constitute inherited predisposition
      to OPLL. In the present study, a strong allelic association with non-OPLL (p =
      0.0003) was observed with an intron 6 polymorphism [intron 6 (-4A)], in which the
      intron 6 (-4A) allele is more frequently observed in non-OPLL subjects than in
      OPLL patients. In addition, a newly identified polymorphism in exon 6 [exon 6
      (+28A)] was in linkage disequilibrium with the intron 6 (-4A). The functional
      impact of the polymorphisms was analyzed by comparing the differences in
      messenger RNA (mRNA) splicing by reverse-transcription polymerase chain reaction
      (RT-PCR) analysis in cultured cells from the interspinous ligament and an in
      vitro exon trapping study. The intron 6 (-4A) allele resulted in skipping exon 6
      and retaining exon 7, while the exon 6 (+28A) allele was not associated with
      alteration in mRNA splicing. Similar mRNA species were observed in
      undifferentiated osteoblast (Ob) cells and in cells from posterior longitudinal
      ligament of non-OPLL subjects. The region containing exons 6-8 is an acidic
      subdomain presumably exposed to the surface that could interact with molecules of
      the extracellular matrix. Accordingly, retaining exon 7 together with removal of
      exon 6 observed in intron 6 (-4A) could play a protective role in the ectopic
      ossification process because the same pattern was observed in undifferentiated Ob
      cells and nonossified posterior longitudinal ligament cells.

PMID- 11341342
TI  - Amylin and bone metabolism in streptozotocin-induced diabetic rats.
AB  - Amylin (AMY) is a 37 amino acid peptide cosecreted with insulin (INS) by
      pancreatic beta-cells and absent in type 1 diabetes, a condition frequently
      associated with osteopenia. AMY binds to calcitonin receptors, lowers plasma
      calcium concentration, inhibits osteoclast activity, and stimulates osteoblasts.
      In the present study, we examined the effects of AMY replacement on bone loss in
      a streptozotocin (STZ)-induced rodent model type 1 diabetes. Of 50 male Wistar
      rats studied, 40 were made diabetic with intraperitoneal STZ (50 mg/kg; plasma
      glucose concentrations > 11 mM within 5 days). Ten nondiabetic control (CONT)
      rats received citrate buffer without STZ. Diabetic rats were divided into four
      groups (n = 10/group) and injected subcutaneously with rat AMY (45 mg/kg), INS
      (12 U/kg), both (same doses), or saline (STZ; diabetic controls) once per day.
      After 40 days of treatment and five 24-h periods of urine collection for
      deoxypyridinoline (DPD), the animals were killed, blood was sampled, and femurs
      were removed. The left femur was tested for mechanical resistance (three-point
      bending). The right femur was tested for total, diaphyseal (cortical bone), and
      metaphyseal (trabecular bone) bone densities using dual-energy X-ray
      absorptiometry (DXA). Bone was ashed to determine total bone mineral (calcium)
      content. None of the treatments had any significant effect on femoral length and
      diameter. Untreated diabetic rats (STZ; 145+/-7N) had lower bone strength than
      did nondiabetic CONT (164+/-38; p < 0.05). Total bone mineral density (BMD;
      g/cm2) was significantly lower in STZ (0. 2523+/-0.0076) than in CONT (0.2826+/
      0.0055), as were metaphyseal and diaphyseal densities. Diabetic rats treated with
      AMY, INS, or both had bone strengths and bone densities that were
      indistinguishable from those in nondiabetic CONT. Changes in bone mineral content
      paralleled those for total BMD (T-BMD). Plasma osteocalcin (OC) concentration, a
      marker for osteoblastic activity, was markedly lower in untreated diabetic rats
      (7. 6+/-0.9 ng/ml); p < 0.05) than in nondiabetic CONT (29.8+/-1.7; p < 0.05) or
      than in AMY (20.1+/-0.7; p < 0.05). Urinary DPD excretion, a marker for bone
      resorption, was similar in untreated and AMY-treated diabetic rats (35.0+/-3.1
      vs. 35.1+/-4.4 nmol/mmol creatinine), intermediate in rats treated with INS
      (49.9+/-2.7), and normalized in diabetic rats treated with both agents (58.8+/
      8.9 vs. 63.2+/-4.5 in CONT). Thus, in our STZ rat model of diabetic osteopenia,
      addition of AMY improved bone indices apparently by both inhibiting resorption
      and stimulating bone formation.

PMID- 11341343
TI  - Is there a causal relationship between quantitative ultrasound and the elastic
      constants of cancellous bone?

PMID- 11341344
TI  - Rutin cannot explain the effect of vegetables on bone metabolism.

PMID- 11341345
TI  - Sensitive detection of p53 mutation: analysis by direct sequencing and
      multisequence analysis.
AB  - In a wide variety of tumors, p53 mutations may have prognostic and diagnostic
      value. However, mutational screening methods often are restricted to the core
      domain and, therefore, do not detect all mutations. We improved existing
      sequencing-based mutation analysis methods consisting of direct sequencing of all
      exons of the p53 gene and RNA. Multisequence analysis software was developed and
      applied to increase the sensitivity of mutation identification. Multisequence
      analysis compares a large number of sequences and identifies profiles with
      additional small peaks, potentially indicating a mutation. Concordance between
      blood and tumor sequences indicates polymorphism, whereas discordance indicates a
      mutation. We could detect mutations with a limit of approximately 5% to 10%
      mutated DNA. In our ongoing studies, we applied sequencing-based mutation
      analysis for more than 50 patients with head and neck squamous cell carcinoma and
      identified mutations in more than 95% of all tumors. We encountered some
      differences between the previously published reference p53 sequence and all our
      sequences and identified polymorphism in six regions.

PMID- 11341346
TI  - Detection of serum autoantibodies to tumor suppressor gene p53 with a new enzyme
      linked immunosorbent assay in patients with ovarian cancer.
AB  - Sera from 99 ovarian cancer patients were assayed for serum autoantibodies to p53
      using a newly developed enzyme-linked immunosorbent assay (ELISA). Results were
      compared to the investigation using the former ELISA. The incidence of
      autoantibodies (25%) was lower using the newly developed ELISA as compared to the
      previous results (41%). The results were consistent in 79% of patients (P <
      .001). The incidence of autoantibodies was lower in patients with complete
      remission (19%) as compared to that of patients with recurrence (30%) and before
      primary surgery (26%). No statistically significant correlation was found among
      p53 serum autoantibody status and tumor stage, degree of malignancy, histologic
      subtype, and residual tumor after primary surgery. Use of the newly developed
      ELISA resulted in a higher consensus between immunohistochemically negative and
      autoantibody negative cases. Owing to further purifying of the prepared human
      recombinant p53. the newly developed ELISA seems to be of higher specificity as
      compared to the former ELISA.

PMID- 11341347
TI  - Aberrant expression of cell-cycle regulatory proteins in human mesenchymal
      neoplasia.
AB  - We previously demonstrated that approximately one-half of soft-tissue sarcomas
      were devoid of either pRB, the product of the retinoblastoma gene, or 16, the
      product of the MTS1/CDKN2 gene, while a smaller subset of aggressive mesenchymal
      tumors without metastatic potential did not express RB by immunohistochemistry.
      We now studied the expression of two additional important cell-cycle regulators,
      namely cyclin D1 and p53, in the same cohort of high- and low-grade lesions. In
      the aggregate, our data provide a comprehensive overview of the importance of
      cell-cycle deregulation in mesenchymal neoplasia. Paraffin sections of 58
      sarcomas and 23 soft-tissue tumors of low malignant potential (STT-LMP) were
      reacted with monoclonal antibodies against cyclin D1 and p53, using optimized
      immunohistochemical staining protocols. The staining data were correlated with
      expression of pRB and p15 and with a variety of pathologic parameters. A total of
      33 of 58 sarcomas (57%) and 9 of 23 STT-LMP (39%) overexpressed p53. Fourteen
      sarcomas (24%) and 4 STT-LMP (17%) overexpressed cyclin D1. There was no
      correlation between expression of these two genes and histologic tumor type or
      grade. Loss of RB and loss of p16 or overexpression of cyclin D1 were mutually
      exclusive events. Considering all four cell-cycle regulators, sarcomas had a
      significantly higher abnormality rate than did STT-LMP (P < .005). Only 10% of
      the sarcomas but 39% of STT-LMP showed normal expression of all four gene
      products. Based on our findings, overexpression of cyclin D1 and (presumably
      mutant) p53 appear to be among the most common molecular alterations in human
      mesenchymal neoplasia, and abrogation of cell-cycle control is observed in the
      great majority of sarcomas; it is present significantly less frequently in low
      grade lesions.

PMID- 11341348
TI  - Nonattendance in mammographic screening: a study of intraurban differences in
      Malmo, Sweden, 1990-1994.
AB  - Mammographic screening may reduce breast cancer mortality. Not all women,
      however, come for examination. The objective in this study from Malmo has been to
      assess extent to which the rate of nonattendance varies between residential areas
      with different sociodemographic profiles. The study is based on 32,605 women, 45
      to 68 years old and living in 17 areas, who between 1990 and 1994 were invited to
      screening. Between age groups, the age-specific nonattendance rate ranged from
      31% to 35 % (P < .01). The nonattendance rate was highest for women 65 years or
      older. Between residential areas, age-adjusted nonattendance rates ranged from
      23% to 43% (P < .01). A socioeconomic score was developed to express the
      socioeconomic circumstances in the residential areas and ranged from -7.18 in the
      most deprived area to 5.01 in the least. Nonattendance covaried in an inverse
      fashion with the socioeconomic score (r = -0.78; P < .01). One of three women in
      this urban population did not accept the invitation to mammographic screening.
      Our conclusion is that women in areas with less favorable circumstances seem to
      be less willing to participate.

PMID- 11341349
TI  - Early indicators of the effect of a breast cancer screening program for low
      income women.
AB  - The National Breast and Cervical Cancer Early Detection Program (NBCCEDP) was
      developed to increase screening among low-income women who are uninsured or
      underinsured. This study reports early indicators of the effectiveness of this
      breast screening program in Iowa. Using data from the Census Bureau and the Iowa
      Behavioral Risk Factor Surveillance System, we found that racial and ethnic
      minorities aged 50 to 64 more likely were screened by the NBCCEDP than were their
      counterparts. Data collected by the Iowa BCCEDP showed a breast cancer detection
      rate (7.1 per 1,000 women screened) that was at least three times higher than its
      historical comparison, an indication of the lead time of the screened over the
      nonscreened population. Predictive values positive (referral and biopsy) and
      stage distribution were typically higher than for the national program but lower
      than in other countries. In conclusion, a breast cancer screening program among
      low-income women can be implemented successfully, judged by early indicators of
      program effectiveness.

PMID- 11341350
TI  - A meta-analysis of mammography screening promotion.
AB  - The purpose of this study was to identify factors that influence the
      effectiveness of interventions in increasing women's use of mammography screening
      programs. To this end, we conducted a systematic literature review of studies
      published between 1966 and 1997. In this review, we recorded data about the year
      and country in which studies were completed, the study design, the methods for
      measuring screening rates, various sample characteristics, the nature of the
      intervention, and the resulting screening rates. The PRECEDE model was used as a
      framework to make distinctions between the various interventions. To synthesize
      evidence about the baseline screening rates and the effect of interventions on
      the incidence of mammography screening, we fit random-effects logistic regression
      models. These models revealed that more recent studies (those conducted from 1990
      to 1996) were associated with higher screening rates (odds ratio [OR], 2.1; 95%
      confidence interval [CI], 1.2-3.9). Conversely, those designed to target older
      women (minimum age, 50-65 years) and those set in clinics exhibited smaller
      screening rates (OR, 0.6, 95% CI, 0.3-1.0, and OR, 0.5; 95% CI, 0.3-0.8,
      respectively). The meta-analyses also suggested methodologic issues that must be
      considered before the relative strength of various interventions can be assessed
      rigorously.

PMID- 11341351
TI  - Rhesus D-phenotype does not provide prognostic information additional to TNM
      staging in gastric cancer patients.
AB  - Recently, the Rhesus D-negative phenotype was identified in multivariate analysis
      as an important independent risk factor in gastric cancer patients who underwent
      curative resection. The distribution of Rhesus (Rh) D phenotype was investigated
      in a group of 268 patients who underwent gastrectomy for gastric cancer from June
      1988 to April 1999. After excluding patients with short, potentially guaranteed
      follow-up or who deceased in the postoperative period, the prognostic
      significance of Rh D phenotype was evaluated in a subgroup of 239 patients by Cox
      regression model controlling for gender, age, site, histology, depth of tumor
      invasion (T), node metastasis (N), and type of resection (R). Two hundred and
      thirty-six patients (88.1%) presented an Rh+ phenotype and 32 (11.9%) presented
      an Rh- phenotype. A significant association was found between Rh D- phenotype and
      the presence of residual tumor after surgery (P = .01). The cumulative 5-year
      survival rate (95% confidence interval) was 37.3% (18.1-56.6) in patients with Rh
      phenotype and 47.0% (39.2-54.4) in patients with Rh+ phenotype. The Rh D
      phenotype did not affect survival independently either in univariate analysis (P
      = .27) or in multivariate analysis (P = .55). The relative risk of death in D
      negative versus D-positive patients decreased from 1.36 (95% confidence interval,
      0.80-2.30) in univariate analysis to 0.84 (0.47-1.49) in multivariate analysis
      after controlling for depth of tumor invasion, lymph node metastases, and type of
      resection. Our study did not confirm the prognostic significance of Rh D
      phenotype in gastric cancer patients.

PMID- 11341352
TI  - Routine endoscopy using electronic endoscopes for gastric cancer diagnosis:
      retrospective study of inconsistencies between endoscopic and biopsy diagnoses.
AB  - To clarify the actual conditions and problems encountered in the diagnosis of
      gastric cancer during routine endoscopic examinations using electronic
      endoscopes, a retrospective study of cases that had shown inconsistencies between
      the endoscopic and biopsy diagnoses was conducted. The subjects were 5,640
      patients who had undergone gastric biopsies. They were selected from among 18,248
      patients in whom upper gastrointestinal endoscopy had been performed between July
      1992 and July 1997 at the National Cancer Center Hospital East. The study was
      conducted focusing on macroscopic type, size, location, and pathologic findings
      of the lesions. Cases showing inconsistencies between the endoscopic and biopsy
      diagnoses comprised 2.7% of all biopsy cases (150 of 5,640). Most of these
      inconsistently diagnosed lesions were less than 20 mm in diameter. The frequency
      of inaccurate diagnosis for depressed lesions in the areas of upper and middle
      thirds of the stomach from the lesser curvature to the posterior wall was
      significantly higher in the inconsistent group, compared with the accurate
      diagnoses from the control group. In diagnostic reviews of depressed lesions,
      46.0% (46 of 100) were diagnosed accurately, but cases with fewer malignant
      indices were recognized. These results indicate that diagnostic accuracy must be
      enhanced through objective biopsy-implementation standards and the use of image
      processing in using diagnostic methods that employ electronic endoscopes.

PMID- 11341353
TI  - Measuring complete diagnostic evaluation in colorectal cancer screening.
AB  - Complete diagnostic evaluation, or CDE (i.e., a colonoscopy or combined barium
      enema X-ray and flexible sigmoidoscopy) is recommended for individuals who have
      an abnormal screening fecal occult blood test result. Accurate measures of CDE
      use are needed in colorectal cancer (CRC) screening programs. This study compares
      the sensitivity and specificity of different methods for measuring CDE
      recommendation and performance. We identified 17 primary-care practices with 120
      patients who had a positive fecal occult blood test result in a CRC screening
      program operated by a managed-care organization. Approaches used to measure CDE
      recommendation and performance included external chart audit (ECA) only; internal
      chart audit (ICA) only; administrative data review (ADR) of electronic claims
      data; ICA plus ADR; and ECA plus ADR (the "gold standard"). Sensitivity and
      specificity of each method were assessed relative to CDE recommendation and
      performance as measured by ECA plus ADR. For CDE recommendation, sensitivity
      measures were ECA only, 0.926; ICA only, 0.790; ADR only, 0.617; and ICA plus
      ADR, 0.901. The specificity of each method for CDE recommendation was no less
      than 0.95. In terms of CDE performance, sensitivity measures were ECA only,
      0.877; ICA only, 0.790; ADR only, 0.877; and ICA plus ADR, 0.965. The specificity
      of each method for CDE performance was 1.0. The ICA-plus-ADR method was a highly
      sensitive and specific measure of CDE use. This method should be considered in
      situations that involve primary-care physician follow-up of patients with
      abnormal CRC screening test results.

PMID- 11341354
TI  - Investigating the role of immunomodulation for colon cancer prevention: results
      of an in vivo dose escalation trial of levamisole with immunologic endpoints.
AB  - The potential role of immunomodulatory agents for colon cancer prevention has not
      been studied systematically. Levamisole (LMS), which is immunostimulatory, is
      synergistic with 5-fluorouracil in the adjuvant therapy of patients with stage
      III colon cancer. This pilot study was initiated to explore the potential utility
      of LMS as a colon cancer prevention agent and to define the minimum dose at which
      it retains potentially beneficial effects on the immune system. Normal volunteers
      were treated over 3 days with LMS at four different dose levels and were
      monitored for toxicity and immunologic changes. Immunologic endpoints included
      lymphocyte antigen expression, serum cytokine levels, and two new ex vivo assays
      that defined LMS's activity in modulating T-helper-1 (Th1) cytokine production.
      In addition, in vitro dose-response analyses of LMS's effects on cellular immune
      function were performed. LMS was tolerated without toxicity at low dosages only.
      Significant increases (P < .0001) in the proportion of peripheral blood
      mononuclear cells expressing the natural killer antigen CD16 were noted at all
      dose levels. LMS did not alter serum cytokine levels and only minimally affected
      Th1 cellular immune function. In vitro analysis demonstrated that LMS is
      synergistic with interleukin 12 in the induction of a Th1 cytokine response at
      very low concentrations (1microM). This study suggests that short-term LMS is
      only minimally immunomodulatory but that immune activity is equivalent at low
      dosages where the medication is better tolerated. Additional, longer-term,
      studies of low-dose LMS as a potential colon cancer chemopreventive agent should
      be considered.

PMID- 11341356
TI  - Cytokeratin 20 as an immunocytochemical marker for detection of urothelial
      carcinoma in atypical cytology: preliminary retrospective study on archived urine
      slides.
AB  - Previous studies have shown that expression of cytokeratin 20 (CK20), a
      constituent of intermediate filaments, is increased in malignant versus benign
      urine samples. To evaluate whether immunocytochemical staining of CK20 on
      archived urine slides could be used as a potential adjunct marker for triage of
      atypical urine cytology, we analyzed a total of 77 archived urine slides obtained
      from a spectrum of patients with various risks of developing urothelial
      carcinoma. These patients were divided into four groups on the basis of initial
      urine cytologic results and subsequent follow-up biopsy findings; group 1 had
      negative results in both evaluations, whereas the results in group 4 were
      positive for both cytology and biopsy. Groups 2 and 3 had a diagnosis of atypical
      urine cytology; however, patients in group 3 had a positive follow-up biopsy, and
      patients in group 2 did not. The Papanicolaou-stained archived urine slides were
      destained and then restained immunocytochemically with monoclonal antibody
      against CK20. With 5% positively stained nonumbrella cells as a threshold, CK20
      was positive in 94.4% of group 3 or 4 patients. In contrast, CK20 was positive in
      27.3% of group 2 patients and in 10.5% of group 1 patients. The overall
      sensitivity and specificity for CK20 for the detection of urothelial carcinoma in
      this population of patients were 94.4% and 80.5%, respectively. This study
      demonstrated that immunocytochemical analysis of CK20 on archived urine slides
      could be used to triage atypical urine cytology into low- and high-risk
      categories and that CK20 might be a simple and useful early detection marker for
      urothelial carcinoma.

PMID- 11341355
TI  - The role of duck hepatitis B virus and aflatoxin B1 in the induction of oxidative
      stress in the liver.
AB  - The aim of our study was to use the Pekin duck model to investigate the
      interactions between hepadnaviral infection and aflatoxin B1 (AFB1) exposure
      including the role of both factors in the induction of oxidative stress in the
      liver. AFB1 exposure of duck hepatitis B virus (DHBV) infected Pekin ducks
      induced a significant increase in viral replication associated with an intense
      biliary ductular cells proliferation. Interestingly, extremely high levels of
      AFB1-DNA adducts (40-120 pmol AFB1-Fapy/mg DNA) and AFB1-albumin adducts (1,500
      3,000 pg AFB1-lys Eq/mg albumin) were detected in duck liver and serum
      respectively, as compared to other animal species exposed to a similar AFB1 dose.
      DHBV infection was found to induce a non-significant increase in AFB1-albumin
      adduct levels in duck serum. During the treatment duration there was no effect on
      formation of oxidative base damage within DNA and no effect on oxidative lipid
      peroxidation following either viral infection or AFB1 exposure. In terms of
      hepatic antioxidant enzymes (catalase, superoxide dismutase (SOD), glutathione
      peroxidase) a significant increase in SOD activity occurred following AFB1
      exposure, but not DHBV infection, but this was observed only after the cessation
      of treatment, when biliary ductular cells proliferation was reduced.

PMID- 11341357
TI  - Ki-67: a proliferative marker that may predict pulmonary metastases and mortality
      of primary osteosarcoma.
AB  - Alterations in Ki-67 activity have been associated with tumor progression and
      poor outcome in cancer patients. This study was undertaken to identify the
      potential of this proliferative marker as a predictor of pulmonary metastases
      (PM) and mortality in osteosarcoma patients. In 38 patients with tissue available
      for immunohistochemical analysis, overexpression of Ki-67 was assessed. Chi
      square and log rank tests were used to determine differences between proportions
      of the marker with PM and mortality and survival distributions respectively. P
      values equal or less than .05 were considered statistically significant. The
      median follow up of this case series was 28 months. Eighteen (47.4%) of 38
      patients developed PM, and 17 (44%) overexpressed Ki-67. We found a high
      frequency of PM (15 of 17) among those cases that overexpressed Ki-67. This
      relationship was significant (P = .000006) when compared to the rest of the
      group. We also found a statistically significant correlation between patients
      with positive and negative Ki-67 scores and higher and lower mortality (P =
      .000962). These findings suggest that Ki-67 overexpression could be used as a
      prognostic molecular marker for the development of PM in osteosarcoma patients.

PMID- 11341358
TI  - Ethnopharmacology in drug discovery: an analysis of its role and potential
      contribution.
AB  - In this paper we discuss some examples of ethnopharmacological research as it has
      been conducted during the last two centuries and look at the current role of this
      discipline in drug discovery (especially with respect to the American and
      European markets) and the further development of these phytotherapeutical
      resources for local use in the countries of origin (ethnopharmacology). Examples
      from 19th century research on curare (Humboldt and Bernard), from the 20th
      century on hallucinogenic mushrooms (Wasson), on Mexican Indian indigenous plants
      (our own research) and of current industry based research are used to illustrate
      the development of this discipline and to highlight the challenges for the
      future.

PMID- 11341359
TI  - Improvement in site-specific intestinal absorption of furosemide by Eudragit L100
      55.
AB  - Furosemide (frusemide) is a weakly acidic diuretic drug. Its absorption is poor
      and variable, in part due to its restricted sites of absorption, mainly the
      stomach. The narrow absorption window of this drug can be explained by pH
      partition theory. The purpose of this study was to investigate the feasibility of
      widening the absorption window of furosemide by controlling the pH in distal
      portions of the gastrointestinal tract with officially used additives.
      Methacrylate copolymer (Eudragit L100-55), hydroxypropylmethylcellulose phthalate
      (HP-55) and hydroxypropylmethylcellulose acetate succinate (AS-MF) were selected
      as additives. The pH of suspensions of these additives was about 4, and the pH
      was adjusted to about 6-7 by the addition of NaOH. The Eudragit L100-55
      suspension was found to be the most resistant to NaOH titration. When Eudragit
      L100-55 was used in an in-situ ileal loop experiment in rats, the pH of the
      intestinal contents was significantly reduced, from 7.9+/-0.1 to 5.7+/-0.1, and
      the plasma concentration of furosemide 15 min after administration was about 3
      times higher than that in controls, 1.81+/- 0.42microg mL(-1) vs 0.63+/-0.08
      microg mL(-1). However, the plasma concentration of [14C] mannitol was not
      changed by the co-administration of Eudragit L100-55. Furthermore, the AUC of
      furosemide was significantly increased by a factor of about 1.6 relative to that
      in controls by the co-administration of Eudragit L100-55, to 21.4+/-4.0 microg h
      mL(-1) from 13.3+/- 3.9 microg h mL(-1), and the gastrointestinal pH in the
      midgut and ileum was significantly reduced, with most of the furosemide remaining
      in these segments at 2 h following the oral administration of furosemide with
      Eudragit L100-55 to rats. These findings clearly demonstrate that the addition of
      Eudragit L100-55 can increase the absorption of furosemide in distal portions of
      the gastrointestinal tract. In conclusion, it is feasible to widen the absorption
      window of furosemide by controlling the pH in distal portions of the
      gastrointestinal tract by the co-administration of Eudragit L100-55.

PMID- 11341360
TI  - Application of pressure-controlled colon delivery capsule to oral administration
      of glycyrrhizin in dogs.
AB  - A colon delivery system has been used to improve the bioavailability of
      glycyrrhizin, a glycoside of glycyrrhetic acid. The bioavailability of
      glycyrrhizin is low when administered in conventional oral galenic dosage forms
      because glycyrrhizin is enzymatically hydrolysed both in the stomach and in the
      intestine. It was reasoned that if large amounts of glycyrrhizin were directly
      delivered to the colon, enzymatic activity should be reduced due to saturation so
      that intact glycyrrhizin could be absorbed into the systemic circulation. Based
      on this assumption, pressure-controlled colon delivery capsules (PCDCs) were used
      as a colon delivery system. Eight types of glycyrrhizin solution were prepared
      and were introduced into PCDCs. After oral administration of the test PCDCs to
      beagle dogs, blood samples were obtained over 24 h and plasma glycyrrhizin
      concentrations were measured by an HPLC method. With PCDCs containing aqueous
      glycyrrhizin and propylene glycol solutions, plasma glycyrrhizin levels were
      extremely low and the bioavailabilities of glycyrrhizin were 0.6% and 0.4%,
      respectively. When Labrasol was added to both types of glycyrrhizin solution, the
      bioavailability was improved to 4.6% for aqueous solution and 3.8% for propylene
      glycol solution. When a surfactant, Polysorbate 80, was added in combination with
      Labrasol, synergistic effects were not obtained. Furthermore, dose-dependent
      effects of Polysorbate 80 were not obtained. Labrasol, which is a component of
      self-emulsifying drug delivery systems (SEDDS), has been shown to strongly
      improve the bioavailability of glycyrrhizin from the colon.

PMID- 11341361
TI  - The effect of selective serotonin reuptake inhibitors (SSRIs) on the
      pharmacokinetics and metabolism of perazine in the rat.
AB  - The aim of this study was to investigate the effect of three selective serotonin
      reuptake inhibitors (SSRIs), fluoxetine, fluvoxamine and sertraline, on the
      pharmacokinetics and metabolism of perazine in a steady state in rats. Perazine
      (10 mg kg(-1), i.p.) was administered twice daily for two weeks, alone or jointly
      with one of the SSRIs. Concentrations of perazine and its two main metabolites (N
      desmethylperazine and 5-sulfoxide) in the plasma and brain were measured 30 min
      and 6 and 12 h after the last dose of the drugs. Of the investigated SSRIs,
      fluoxetine and fluvoxamine significantly increased plasma and brain
      concentrations of perazine (up to 900% and 760% of the control value,
      respectively), their effect being most pronounced after 30 min and 6 h. Moreover,
      simultaneous increases in perazine metabolites concentrations and in the
      perazine/metabolite concentration ratios were observed. Sertraline elevated
      plasma and brain concentrations of perazine after 30 min. In-vitro studies with
      liver microsomes of rats treated chronically with perazine, SSRIs ortheir
      combinations showed decreased concentrations of cytochrome P-450 after perazine
      and a combination of perazine and fluvoxamine (vs control), and increased
      concentration after a combination of perazine and fluoxetine (vs perazine-treated
      group). Prolonged treatment with perazine did not significantly change the rate
      of its own metabolism. Chronic administration of fluoxetine or sertraline, alone
      or in a combination with perazine, accelerated perazine N-demethylation (vs
      control or perazine group, respectively). Fluvoxamine had a similar effect. The 5
      sulfoxidation of perazine was accelerated by fluvoxamine and sertraline
      treatment, but the process was inhibited by administration of a combination of
      perazine and fluoxetine or fluvoxamine (vs control). Kinetic studies using
      control liver microsomes, in the absence or presence of SSRIs added in-vitro,
      demonstrated competitive inhibition of both N-demethylation and sulfoxidation by
      the investigated SSRIs. Sertraline was the most potent inhibitor of perazine N
      demethylation but the weakest inhibitor of sulfoxidation. Results of in-vivo and
      in-vitro studies indicate that the observed interaction between perazine and
      SSRIs mainly involves competition for an active site of perazine N-demethylase
      and sulfoxidase. Moreover, increases in the concentrations of both perazine and
      metabolites measured, produced by the investigated drug combinations in-vivo,
      suggest simultaneous inhibition of another, yet to be investigated, metabolic
      pathway of perazine (e.g. aromatic hydroxylation).

PMID- 11341362
TI  - Reversible binding of the novel anti-tumour agent 5,6-dimethylxanthenone-4-acetic
      acid to plasma proteins and its distribution into blood cells in various species.
AB  - The plasma protein binding and distribution in blood cells of the novel anti
      tumour agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA) has been investigated
      in-vitro using filtration and an HPLC method to measure DMXAA. DMXAA (500 microM)
      was extensively bound in plasma from all species with an unbound fraction (fu) of
      4.61+/-1.10 (mouse), 2.59+/-0.32 (rat), 2.02+/-0.48 (rabbit) and 2.07+/-0.23%
      (human). The binding was concentration dependent with DMXAA concentrations > or =
      1,000 microM markedly increasing the fu in the plasma from all species. The
      estimated number of binding sites in plasma were 2.4+/-0.2 (mouse), 1.7+/-0.2
      (rat), 0.8+/-0.1 (rabbit) and 2.1+/- 0.2 (human). The major binding protein in
      human plasma was albumin, with negligible binding to gamma-globulin and alpha1
      acid glycoprotein. There was a significant linear relationship between the
      bound:free DMXAA concentration ratio (Cb/Cu) and albumin concentration in human
      serum albumin solution (r = 0.955; P < 0.05) and in healthy human plasma (r =
      0.998; P< 0.05), but not in plasma from cancer patients (n = 5), nor across
      species. In cancer patients (n = 5) DMXAA had a significantly higher (P < 0.05)
      fu (4.60+/- 0.42%) compared with healthy human plasma (2.07+/-0.23%). In human
      plasma, the fu of DMXAA (500 microM) was significantly reduced by 500 microM
      diazepam (P < 0.05), but not by warfarin, phenylbutazone, salicylic acid,
      ibuprofen or clofibric acid at that concentration. DMXAA significantly reduced
      the binding of dansylsarcosine (a Site-II binder) to HSA, but significantly
      increased the binding of dansylamide (a Site-I binder). Within species, the
      blood:plasma concentration ratio (CBL/CP) of DMXAA was relatively constant
      (mouse, 0.581+/-0.005; rat, 0.667+/-0.025; rabbit, 0.637+/-0.019; human, 0.673+/
      0.103) over the range 50-1000 microM, but increased significantly at DMXAA
      concentrations > 1000 microM in all species except the rabbit. These results
      indicate that significant alterations in DMXAA plasma binding and distribution
      into blood cells occur with increasing concentrations of DMXAA in all species,
      and also that significant interspecies differences exist. It would be more
      appropriate to compare plasma unbound concentrations when assessing DMXAA
      exposure in cancer patients or when extrapolating across species.

PMID- 11341363
TI  - Synthesis and kinetic evaluation of peptide alpha-keto-beta-aldehyde-based
      inhibitors of trypsin-like serine proteases.
AB  - New, synthetic peptide analogues bearing a C-terminal basic alpha-keto-beta
      aldehyde moiety were prepared as novel inhibitors of the trypsin-like serine
      proteases. The compounds, Ac-Leu-Leu-Arg-COCHO, Ac-Arg-Gln-Arg-COCHO and Boc-Val
      Leu-Lys-COCHO were evaluated kinetically against trypsin and three other trypsin
      like serine proteases, tryptase, plasmin and thrombin, all of which are
      implicated as mediators of important disease processes. Results illustrate that
      alpha-keto-beta-aldehydes are potent inhibitors, with similar potency to
      comparable peptide aldehydes, and intriguingly, appearto act, in some instances,
      by a novel mechanism of action. Ac-Leu-Leu-Arg-COCHO, an analogue of the natural
      product leupeptin, is a potent, tight-binding inhibitor of trypsin (Ki(final) =
      1.9 microM), plasmin (Ki(final) = 4.9 microM) and tryptase (Ki(final) = 1.2
      microM) and an irreversible inactivator of thrombin (k2nd 4,500 M(-1).min(-1)).
      Boc-Val-Leu-Lys-COCHO was found to be a tight-binding inhibitor of its target
      protease plasmin (Ki(final) = 3.1 microM) and was inactive against thrombin. Ac
      Arg-Gln-Arg-COCHO was a slow-binding inhibitor of tryptase (Ki(final) = 1.6
      microM) and also irreversibly inactivated trypsin (k2nd = 8,920 M(-1) min(-1)).
      Peptides or peptidomimetics with a C-terminal basic alpha-keto-beta-aldehyde
      function thus provide a useful new molecular template for the development of new
      therapeutic agents against a wide range of disorders, such as coagulopathies and
      asthma, which may be mediated by the aberrant activity of trypsin-like serine
      proteases.

PMID- 11341364
TI  - Characterization and purification of the vitamin K1 2,3 epoxide reductases system
      from rat liver.
AB  - The enzyme vitamin K1 2,3 epoxide reductase is responsible for converting vitamin
      K1 2,3 epoxide to vitamin K1 quinone thus completing the vitamin K cycle. The
      enzyme is also the target of inhibition by the oral anticoagulant, R,S-warfarin.
      Purification of this protein would enable the interaction of the inhibitor with
      its target to be elucidated. To date a single protein possessing vitamin K1 2,3
      epoxide reductase activity and binding R,S-warfarin has yet to be purified to
      homogeneity, but recent studies have indicated that the enzyme is in fact at
      least two interacting proteins. We report on the attempted purification of the
      vitamin K1 2,3 epoxide reductase complex from rat liver microsomes by ion
      exchange and size exclusion chromatography techniques. The intact system
      consisted of a warfarin-binding factor, which possessed no vitamin K1 2,3 epoxide
      reductase activity and a catalytic protein. This catalytic protein was purified
      327-fold and was insensitive to R,S-warfarin inhibition at concentrations up to 5
      mM. The addition of the S-200 size exclusion chromatography fraction containing
      the inhibitor-binding factor resulted in the return of R,S-warfarin inhibition.
      Thus, to function normally, the rat liver endoplasmic reticulum vitamin K1 2,3
      epoxide reductase system requires the association of two components, one with
      catalytic activity for the conversion of the epoxide to the quinone and the
      second, the inhibitor binding factor. This latter enzyme forms the thiol
      disulphide redox centre that in the oxidized form binds R,S-warfarin.

PMID- 11341365
TI  - Inhibition of field stimulation-induced contractions of rabbit vas deferens by
      muscarinic receptor agonists: selectivity of McN-A-343 for M1 receptors.
AB  - Inhibition of the field stimulation-induced twitch responses of the rabbit vas
      deferens by the muscarinic receptor agonist, McN-A-343, has been attributed to
      presynaptic muscarinic receptors of the M1 subtype located on noradrenergic nerve
      terminals. Stimulation of these receptors causes inhibition of transmitter
      release and inhibition of the contractile response. However, the selectivity of
      McN-A-343 for M1 receptors has been questioned and this throws doubt on whether
      the prejunctional receptors of the rabbit vas deferens are of the M1 subtype. In
      this study we have undertaken a comprehensive re-evaluation of the inhibition of
      prostatic and epididymal portions of the rabbit isolated field-stimulated vas
      deferens by several agonists, including McN-A-343, and quantified the antagonism
      by M1-selective antagonists, pirenzepine and telenzepine. Prostatic and
      epididymal portions of vasa deferentia from New Zealand White rabbits were
      immersed in a low Ca2+ Krebs solution at 32+/-0.5 degrees C gassed with 5% CO2 in
      oxygen. Yohimbine (1.0mM) was present throughout to block prejunctional alpha2
      adrenoceptors. Field stimulation was applied by repeated application of single
      pulses (30 V, 0.05 Hz, 0.5 ms) and isometric contractions recorded. Carbachol and
      oxotremorine initially potentiated the epididymal contractions but at higher
      concentrations there was inhibition. In the prostatic portion, oxotremorine only
      inhibited. McN-A-343 produced inhibitory responses only in both epididymal and
      prostatic portions. Pirenzepine shifted the concentration-response curves forthe
      inhibitory responses to oxotremorine to the right. However, the potentiation of
      the twitches also became more apparent with the lower concentrations of
      oxotremorine. Schild plots for the antagonism by pirenzepine yielded pA2 values
      of 7.96+/-0.004 and 7.7+/-0.02 for the epididymal and prostatic portions,
      respectively. The concentration-response curves for the inhibition of twitches by
      McN-A-343 were displaced to the right in a parallel manner by pirenzepine in both
      prostatic and epididymal portions with no potentiation of the twitches. The
      Schild plot for this antagonism generated pA2 values of 7.68+/-0.01 and 8.07+/
      0.01, respectively. Telenzepine caused parallel shifts of the McN-A-343
      concentration-response curves to the right in prostatic portions, the pA2 value
      being 8.70+/-0.13. Telenzepine (10(-7) M) abolished the inhibitory effect of
      carbachol to reveal only concentration-dependent potentiation of the
      contractions. The Schild plot for antagonism of this contractile effect yielded a
      pA2 value (7.07+/-0.09) that was significantly less by almost two orders of
      magnitude (1.70) than the value for the antagonism by telenzepine of the McN-A
      343-induced inhibitory response. The pA2 values of pirenzepine and telenzepine
      against the inhibitory responses of the rabbit vas deferens are consistent with
      the involvement of M1 receptors. This leads to the conclusion that McN-A-343
      causes inhibition through this receptor type. The doubts concerning the
      selectivity of McN-A-343 for M1 receptors are therefore unfounded. The fact that
      McN-A-343 does not display a selective binding profile suggests that its
      selectivity does not arise from affinity differences but probably resides in its
      intrinsic efficacy.

PMID- 11341366
TI  - Molecular and functional identification of large neutral amino acid transporters
      LAT1 and LAT2 and their pharmacological relevance at the blood-brain barrier.
AB  - We present here the evidence of molecular and functional expression of LAT1 and
      LAT2, subunits of the large neutral amino acid transporter system L, in cultured
      brain capillary endothelial cells of the rat. By means of the RT-PCR method,
      transcripts of LAT1, LAT2 and heavy chain of 4F2 antigen (4F2hc) were detected in
      rat primary cultured brain capillary endothelial cells (BCECs) and immortalized
      subline, RBEC1. The uptake properties of RBEC1, such as [3H]leucine and L
      [3H]DOPA uptake, were similar to those of primary cultured BCECs. So, RBEC1 may
      retain almost native properties of the large neutral amino acid uptake
      activities. [3H]Leucine uptake by RBEC1 showed two saturable components and the
      Km values of the high- and low-affinity components were 8.92+/-3.18 and 119+/-45
      microM, respectively. The Km value of the high-affinity component agreed well
      with that of LAT1 and the amino acid transport selectivity of RBEC1 was similar
      to that of LAT1. Therefore, it is suggested that LAT1 is important at the blood
      brain barrier of rats. Additionally, the Km value of the low-affinity component
      was similar to that of LAT2. These observations indicate that LAT1 and LAT2 are
      involved as transporters for large neutral amino acids at the blood-brain
      barrier. Additionally, we concluded that RBEC1 is useful as an in-vitro model for
      evaluation of the pharmacological relevance of system L at the blood-brain
      barrier.

PMID- 11341367
TI  - 1,8-cineole protects against liver failure in an in-vivo murine model of
      endotoxemic shock.
AB  - The effects of 1,8-cineole on D-galactosamine/lipopolysaccharide (GalN/LPS)
      induced shock model of liver injury was investigated in mice. The co
      administration of GalN (700 mg kg(-1), i.p.) and LPS (5 microg kg(-1), i.p.)
      greatly elevated serum concentrations of tumour necrosis factor-alpha (TNF
      alpha), alanine aminotransferase and aspartate aminotransferase, and induced
      massive hepatic necrosis and lethality in 100% of control mice. Pretreatment with
      1,8-cineole (400 mg kg(-1), p.o.) and dexamethasone (1 mg kg(-1), s.c.), 60 min
      before GalN/LPS, offered complete protection (100%) against the lethal shock and
      acute elevation in serum TNF-alpha and serum transaminases. Hepatic necrosis
      induced by GalN/LPS was also greatly reduced by both 1,8-cineole and
      dexamethasone treatment. The results indicate that 1,8-cineole protects mice
      against GalN/LPS-induced liver injury through the inhibition of TNF-alpha
      production, and suggest that 1,8-cineole may be a promising agent to combat
      septic-shock-associated pathologies.

PMID- 11341368
TI  - The evaluation of novel mixed metal hydroxy-carbonates as phosphate binders: an
      in-vivo study in the rat.
AB  - A number of novel phosphate binders based on mixed metal hydroxide structures
      incorporating Fe and Ca, or Fe and Mg (classified as CT, Crosfield test
      compounds), were compared with the established phosphate binders Mg(OH)2,
      Al(OH)3, CaCO3 and a commercial hydrotalcite (Al- and Mg-based) using a rat
      model. The changes in urine and soluble faecal phosphate were used to evaluate
      efficacy of phosphate binding. The binders were mixed into a standard rat
      maintenance food at a concentration of 1% (w/w). Four rats were used for each
      binder study group and fed over 7 days. Urine and faeces were collected (in a
      metabolic cage) over the last 24-h study period and the phosphate content
      measured. The urinary phosphate was significantly reduced (P < 0.001) with CTFeCa
      (72+/-44 microm), CTFeMg (13+/-4 microm), CT100 (26+/-11 microm), and Mg(OH)2
      (65+/-53 microm), compared with control (766+/-188 microm), Al(OH)3 (1,256+/-279
      microm), and CaCO3 (857+/-25 microm). The soluble phosphate content of the faeces
      was significantly reduced (P < 0.05) by up to 60 % with CTFeCa, CTFeMg and
      Mg(OH)2, and up to 40% with CT100 and Al(OH)3, compared with 30% in controls and
      10% with CaCO3. The new mixed metal hydroxy-carbonate compounds based on FeCa or
      FeMg are effective phosphate binders in-vivo and warrant further testing in
      patients.

PMID- 11341369
TI  - Antinociceptive effect of U-50488H, a kappa-opioid agonist, in streptozotocin
      induced diabetic mice.
AB  - We compared the antinociceptive activity of a kappa-opioid agonist, U-50488H, in
      streptozotocin-induced diabetic mice with that in non-diabetic mice.
      Subcutaneously administered U-50488H (3 and 10 mg kg(-1)) showed a more potent
      antinociceptive effect, as evaluated by the tail-pressure method, in diabetic
      mice than in non-diabetic mice. Increased antinociceptive activity of U-50488H
      observed in diabetic mice was also observed in mice given U-50488H intrathecally
      (3 and 10 microg). However, there were no differences observed between diabetic
      and non-diabetic mice given U-50488H intracerebroventricularly (3 and 10 microg).
      Although the antinociceptive effect of U-50488H (3 mg kg(-1), s.c.) in non
      diabetic mice was increased by treatment with PD135158 (100 ng, i.c.v.), a
      cholecystokininB (CCKB) antagonist, the antinociceptive activity of U-50488H
      which was enhanced in diabetic mice was not influenced by PD135158. Moreover, the
      increased antinociceptive activity of U-50488H (3 mg kg(-1), s.c.) in diabetic
      mice diminished when desulfated octapeptide of cholecystokinin (3-100 ng,
      i.c.v.), a CCKB agonist, was administered. These results suggested that diabetic
      mice were selectively hyper-responsive to spinal kappa-opioid receptor-mediated
      antinociception. The function of the analgesia inhibitory system in which
      cholecystokinin is used as a transmitter might be diminished in diabetic mice.

PMID- 11341370
TI  - Effect of gamma-butyrobetaine on fatty liver in juvenile visceral steatosis mice.
AB  - We pharmacokinetically examined the effect of gamma-butyrobetaine, a precursor of
      L-carnitine, on the change of fatty acid metabolism in juvenile visceral
      steatosis (JVS) mice, which have systemic L-carnitine deficiency due to lack of L
      carnitine transporter activity. The concentrations of total free fatty acid
      (FFA), palmitic acid and stearic acid in the liver of JVS mice were significantly
      higher than those in wild-type mice. After intravenous administration of gamma
      butyrobetaine (50 mg kg(-1)), the concentration of L-carnitine in the plasma of
      JVS mice reached about twice that of the control level and levels in the brain,
      liver and kidney were also significantly increased, whereas those in wild-type
      mice hardly changed. Although the plasma concentrations of FFA in both types of
      mice were unchanged after administration of gamma-butyrobetaine, the
      concentrations of palmitic acid and stearic acid were significantly decreased. In
      particular, the liver concentration of FFA in JVS mice was decreased to the wild
      type control level, accompanied by significant decreases in long-chain fatty
      acids, palmitic acid and stearic acid, whereas those in wild-type mice were not
      changed. These results suggest that gamma-butyrobetaine can be taken up into
      organs, including the liver, of JVS mice, and transformed to L-carnitine.
      Consequently, administration of gamma-butyrobetaine may be more useful than that
      of L-carnitine itself for treatment of primary deficiency of carnitine due to a
      functional defect of the carnitine transporter.

PMID- 11341371
TI  - The lipid-lowering effect of trans-dehydrocrotonin, a clerodane diterpene from
      Croton cajucara Benth. in mice fed on high-fat diet.
AB  - The clerodane diterpene trans-dehydrocrotonin extracted and isolated from the
      stem bark of Croton cajucara Benth. was investigated for its lipid-lowering
      effect in mice fed on a high-fat diet. Mice fed on a high-fat diet for a two-week
      period demonstrated significantly increased blood levels of total cholesterol and
      triglycerides, compared with normal controls. Oral treatment with trans
      dehydrocrotonin at a dose of 25 or 50 mg kg(-1) daily markedly suppressed the
      high-fat-diet associated rise in total cholesterol and triglyceride levels. The
      hypocholesterolaemic effect of trans-dehydrocrotonin was more prominent at the
      dose of 50 mg kg(-1) with significant decreases in high-density lipoprotein, very
      low-density lipoprotein and low-density lipoprotein cholesterol levels. The lower
      atherogenic index of the trans-dehydrocrotonin-treated groups suggests the
      hypolipidaemic potential of this plant-based drug. These results indicate that
      orally administered trans-dehydrocrotonin is effective in suppressing high-fat
      diet-induced hyperlipidaemia in mice and suggest its likely beneficial use as
      anti-atherogenic agent.

PMID- 11341372
TI  - Interactions among proteins and hydrophobically modified polyelectrolytes.
AB  - A special class of hydrophobically modified polyelectrolytes was studied wherein
      poly(acrylic acid) (PAA) was conjugated with Pluronic F127 NF surfactant. The
      Pluronic-PAA copolymer solutions form gels at low concentrations when exposed to
      bodytemperature. Such gels possess enhanced retention in topical applications.
      Circular dichroism spectra indicate that tertiary structures of human insulin,
      haemoglobin, and albumin were stabilized in solutions of Pluronic-PAA.
      Aggregation of insulin in gelled solutions of Pluronic-PAA was impeded as
      demonstrated in shaking tests. The presence of Pluronic-PAA hindered the insulin
      degradation by alpha-chymotrypsin by at least 7-fold. Extraction of calcium ions
      from trypsin by Pluronic-PAA led to the dramatic changes in the tertiary
      structure and total loss of enzymatic activity, suggesting that Pluronic-PAA
      could inhibit tryptic degradation of proteins.

PMID- 11341373
TI  - Turbidimetric and HPLC assays for the determination of formulated lysozyme
      activity.
AB  - In several studies lysozyme has been employed as a model protein to investigate
      the effects of formulation factors upon biological activity. The aim of this work
      was to develop and validate an HPLC technique to assay lysozyme and to compare
      the results with biological activity determined from a validated turbidimetric
      assay. The turbidimetric assay was based upon the lytic action of lysozyme on
      Micrococcus lysodeikticus cells, whilst the reverse-phase HPLC assay employed an
      acetonitrile gradient in 0.1% trifluoroacetic acid. The limits of detection and
      quantification were 3.84 and 6.24 microg mL(-1) for HPLC assay, whilst the
      corresponding values for turbidimetric assay were 1.94 and 3.86 microg mL(-1).
      The methods were used to monitor the loss of enzyme activity after heating.
      Lysozyme concentrations determined from HPLC peak height were found to correlate
      (r2 = 0.9963) with those obtained from turbidimetric assay.

PMID- 11341374
TI  - Pro-inflammatory activity of contaminating DNA in hyaluronic acid preparations.
AB  - Hyaluronic acid (HA), an abundant non-sulfated glycosaminoglycan component of the
      extracellular matrix, has applications in drug delivery, tissue engineering and
      as an ingredient in cosmetics. HA preparations containing high-molecular-weight
      polymers are also used in the treatment of inflammatory disorders such as
      arthritis and interstitial cystitis. Low-molecular-weight fragments derived from
      HA have been reported to induce pro-inflammatory cytokines such as IL-12 and TNF
      alpha, and could therefore potentially exacerbate existing inflammation. We
      therefore examined the pro-inflammatory activity of HA preparations, since
      inflammatory reactions are known to occur following administration of HA. We
      tested low-molecular-weight fragments obtained from seven different HA
      preparations, either by sonication (approximately equals 3 x 10(5) Da) or by
      hyaluronidase digestion (approximately equals 1 x 10(4) Da), for the ability to
      induce the synthesis of IL-12 and TNF-alpha by human monocytic cells. We found
      that two of the seven HA preparations tested stimulated the synthesis of IL-12
      and TNF-alpha by human monocytic cells. We unexpectedly found that the induction
      of IL-12 and TNF-alpha by these HA preparations was not due to their degradation
      to low-molecular-weight fragments, since their native high-molecular-weight forms
      possessed the same ability to stimulate IL-12 and TNF-alpha synthesis, but was
      due to the presence of contaminating DNA. Treatment of these two HA preparations
      with deoxyribonuclease I abrogated or reduced the induction of IL-12 and TNF
      alpha. It is clear from this study that HA preparations can induce the synthesis
      of pro-inflammatory cytokines by monocytes. The ability of HA to act as a pro
      inflammatory mediator may not, however, be related to the presence of low
      molecular-weight HA fragments, but to the presence of DNA. The presence of pro
      inflammatory DNA in HA preparations should be evaluated before its use, not only
      for the treatment of patients with inflammatory disorders, but also before many
      other applications.

PMID- 11341375
TI  - Cryptofolione derivatives from Cryptocarya alba fruits.
AB  - Cryptofolione (1) and the new cryptofolione derivative 6-(4,6-dimethoxy-8-phenyl
      octa-1,7-dienyl)-4-hydroxy-tetrahydro-pyran-2-one (2) were isolated from the
      fruits of Cryptocarya alba. The structures were elucidated by spectroscopic
      methods. Cryptofolione showed activity towards Trypanosoma cruzi trypomastigotes,
      reducing their number by 77% at 250 microg mL(-1). Cryptofolione showed moderate
      cytotoxicity in both macrophages and T. cruzi amastigotes. It also displayed a
      mild inhibitory effect on the promastigote form of Leishmania spp. As both
      cytotoxic and trypanocidal effects are similar, the compound presented little
      selectivity in our assay models.

PMID- 11341376
TI  - Tea consumption modulates hepatic drug metabolizing enzymes in Wistar rats.
AB  - The antioxidant, antimutagenic and anticarcinogenic activities of green tea and
      its polyphenols have been reported. As bioactivation of the precarcinogens and
      detoxification of ultimate carcinogens are mainly carried out by hepatic
      metabolizing enzymes, we have investigated the modulation of these enzyme
      activities subsequent to tea consumption in rats. Female Wistar rats were divided
      into eight groups (n = 5). Six groups were given aqueous solutions (2%, w/v) of
      six different teas (New Zealand green tea, Australian green tea, Java green tea,
      Dragon green tea, Gunpowder green tea or English Breakfast black tea) as the sole
      source of fluid. One group was given a standard green tea extract (0.5%, w/v)
      while the control group had free access to water. At the end of four-weeks
      treatment, different cytochrome P450 (CYP) isoform and phase II enzyme activities
      were determined by incubation of the liver microsomes or cytosols with
      appropriate substrates. CYP 1A2 activity was markedly increased in all the tea
      treatment groups (P < 0.05). CYP 1A1 activity was increased significantly in most
      of the groups except for the Madura, Gunpowder, and Java green tea-treatment
      groups. Cytosolic glutathione-S-transferase activity was significantly increased
      (P< 0.05) in the New Zealand, Gunpowder, and Java green tea-treatment groups. The
      microsomal UDP-glucuronosyl transferase activity remained unchanged or was
      moderately increased in most of the groups. The balance between the phase I
      carcinogen-activating enzymes and the phase II detoxifying enzymes could be
      important in determining the risk of developing chemically-induced cancer.

PMID- 11341377
TI  - Buchu (Agathosma betulina and A. crenulata, Rutaceae) essential oils: their
      pharmacological action on guinea-pig ileum and antimicrobial activity on
      microorganisms.
AB  - The mode of action of essential oils from two buchu species (Agathosma betulina
      and A. crenulata, Rutaceae) from the Cape region of South Africa has been studied
      on smooth muscle in-vitro using guinea-pig ileum. At high concentration, the oils
      had an initial spasmogenic activity followed by spasmolysis. The spasmolytic
      action was post-synaptic, not atropine-like and did not involve adrenoceptor or
      guanylyl cyclase activation. In the presence of the phosphodiesterase inhibitor
      rolipram, the spasmolytic action of A. betulina was significantly increased
      whilst that due to A. crenulata was also increased but not to a significant
      level. These results suggested a mode of action for the oils involving cyclic
      adenosine monophosphate. In addition, A. betulina appeared to block calcium
      channels but this was not seen with A. crenulata, possibly because the initial
      spasmogenic activity complicated the study of its spasmolytic action. Neither
      essential oil (10 microL, undiluted) demonstrated antimicrobial action against
      Enterococcus hirae and Pseudomonas aeruginosa but very low activity was observed
      against Escherichia coli, Saccharomyces cerevisiae and Staphylococcus aureus,
      suggesting little potential for these oils as antimicrobial agents/preservatives.

PMID- 11341378
TI  - Authors do not believe article provides evidence of vaccine efficacy.

PMID- 11341379
TI  - Questions evaluation of refractometer.

PMID- 11341380
TI  - Assessment of a point-of-care instrument for identification of primary hemostatic
      disorders in dogs.
AB  - OBJECTIVE: To assess a point-of-care instrument for identification of primary
      hemostatic disorders in dogs. ANIMALS: 29 healthy dogs and 23 nonanemic dogs with
      primary hemostatic disorders (thrombocytopenia, n = 6; thrombopathia, 6; von
      Willebrand disease [vWD], 11). PROCEDURE: Citrated blood was obtained and closure
      times (CT) were determined by measuring the time required for occlusion of an
      aperture by a platelet plug within the point-of-care instrument. Reference ranges
      for CT were established, and CT were determined for dogs with primary hemostatic
      disorders. RESULTS: CT measured with adenosine diphosphate as the platelet
      agonist (ADP-CT) ranged from 52 to 86 seconds for healthy dogs (mean +/- 2 SD, 67
      +/- 7.8 seconds; median, 65 seconds), and CT measured with epinephrine as the
      agonist (EPI-CT), from 97 to 225 seconds (151 +/- 38 seconds; 148 seconds). In
      thrombocytopenic dogs, ADP- and EPI-CT were prolonged (> 165 and > 264 seconds,
      respectively). Five of 6 dogs with thrombopathia had prolonged ADP-CT, whereas
      EPI-CT was prolonged in all 6 dogs. In all dogs with vWD, ADP-CT was prolonged;
      EPI-CT was prolonged in 10 of these dogs. Sensitivity and specificity for ADP-CT
      were 95.7 and 100%, respectively, and positive and negative predictive values,
      100 and 96.7%, respectively, whereas for EPI-CT, these values were 95.7 and
      82.8%, respectively, and 81.5 and 96%, respectively. CONCLUSIONS AND CLINICAL
      RELEVANCE: The point-of-care instrument allowed quick assessment of primary
      hemostasis in nonanemic dogs. Use of this instrument may be helpful for making
      decisions regarding management of dogs with primary hemostatic disorders.

PMID- 11341381
TI  - Spectrum analysis of respiratory sounds in exercising horses with experimentally
      induced laryngeal hemiplegia or dorsal displacement of the soft palate.
AB  - OBJECTIVE: To record respiratory sounds in exercising horses and determine
      whether spectrum analysis could be use to identify sounds specific for laryngeal
      hemiplegia (LH) and dorsal displacement of the soft palate (DDSP). ANIMALS: 5
      Standardbred horses. PROCEDURE: Respiratory sounds were recorded and pharyngeal
      pressure and stride frequency were measured while horses exercised at speeds
      corresponding to maximum heart rate, before and after induction of LH and DDSP.
      RESULTS: When airway function was normal, expiratory sounds predominated and
      lasted throughout exhalation. After induction of LH, expiratory sounds were
      unaffected; however, all horses produced inspiratory sounds characterized by 3
      frequency bands centered at approximately 0.3, 1.6, and 3.8 kHz. After induction
      of DDSP, inspiratory sounds were unaffected, but a broad-frequency expiratory
      sound, characterized by rapid periodicity (rattling) was heard throughout
      expiration. This sound was not consistently detected in all horses. CONCLUSIONS
      AND CLINICAL RELEVANCE: The technique used to record respiratory sounds was well
      tolerated by the horses, easy, and inexpensive. Spectrum analysis of respiratory
      sounds from exercising horses after experimental induction of LH or DDSP revealed
      unique sound patterns. If other conditions causing airway obstruction are also
      associated with unique sound patterns, spectrum analysis of respiratory sounds
      may prove to be useful in the diagnosis of airway abnormalities in horses.

PMID- 11341382
TI  - Comparison of bronchoalveolar lavage fluid obtained from Mannheimia haemolytica
      inoculated calves with and without prior treatment with the selectin inhibitor
      TBC1269.
AB  - OBJECTIVES: To determine effects of selectin inhibitor TBC1269 on neutrophil
      infiltration, and neutrophil-associated injury during pneumonia induced by
      Mannheimia haemolytica and concentration of antimicrobial anionic peptide (AAP)
      in bronchoalveolar lavage fluid (BALF) as well as antimicrobial activity of BALF
      from healthy (control) neonatal calves, neonatal calves with M haemolytica
      induced pneumonia, neonatal calves with prior treatment with TBC1269, and adult
      cattle. ANIMALS: Eighteen 1- to 3-day-old calves and 9 adult cattle. PROCEDURE:
      Calves were inoculated with M haemolytica or pyrogen-free saline (0.14M NaCl)
      solution into the right cranial lung lobe, and BALF was collected 2 or 6 hours
      after inoculation. Thirty minutes before and 2 hours after inoculation, 4 calves
      received TBC1269. The BALF collected from 9 adult cattle was used for comparison
      of BALF AAP concentration and antimicrobial activity. Protein concentration and
      neutrophil differential percentage and degeneration in BALF were determined. An
      ELISA and killing assay were used to determine BALF AAP concentration and
      antimicrobial activity, respectively. RESULTS: Total protein concentration was
      significantly decreased in BALF from calves receiving TBC1269. Similar
      concentrations of AAP were detected in BALF from all calves, which were 3-fold
      higher than those in BALF from adult cattle. However, BALF from neonates had
      little or no anti-M haemolytica activity. CONCLUSIONS AND CLINICAL RELEVANCE:
      These results suggest that TBC1269 decreases pulmonary tissue injury in neonatal
      calves infected with M haemolytica. Although AAP is detectable in neonatal BALF
      at 3 times the concentration detected in adult BALF, neonatal BALF lacks
      antimicrobial activity for M haemolytica.

PMID- 11341383
TI  - Pharmacokinetics of phenylbutazone and its metabolite oxyphenbutazone in
      miniature donkeys.
AB  - OBJECTIVE: To describe the pharmacokinetics of phenylbutazone and oxyphenbutazone
      after IV administration in miniature donkeys. ANIMALS: 6 clinically normal
      miniature donkeys. PROCEDURE: Blood samples were collected before and 5, 10, 20,
      30, 45, 60, 90, 120, 180, 240, 300, 360, and 480 minutes after IV administration
      of phenylbutazone (4.4 mg/kg of body weight). Serum was analyzed in triplicate by
      use of high-performance liquid chromatography for determination of phenylbutazone
      and oxyphenbutazone concentrations. The serum concentration-time curve for each
      donkey was analyzed separately to estimate model-independent pharmacokinetic
      variables. RESULTS: Serum concentrations decreased rapidly after IV
      administration of phenylbutazone, and they reached undetectable concentrations
      within 4 hours. Values for mean residence time ranged from 0.5 to 3.0 hours
      (median, 1.1 hour), whereas total body clearance ranged from 4.2 to 7.5 ml/kg/min
      (mean, 5.8 ml/kg/min). Oxyphenbutazone appeared rapidly in the serum; time to
      peak concentration ranged from 13 to 41 minutes (mean, 26.4 minutes), and peak
      concentration in serum ranged from 2.8 to 4.0 mg/ml (mean, 3.5 microg/ml).
      CONCLUSION AND CLINICAL RELEVANCE: Clearance of phenylbutazone in miniature
      donkeys after injection of a single dose (4.4 mg/kg, IV) is rapid. Compared with
      horses, miniature donkeys may require more frequent administration of
      phenylbutazone to achieve therapeutic efficacy.

PMID- 11341384
TI  - Relationship between mean body surface temperature measured by use of infrared
      thermography and ambient temperature in clinically normal pigs and pigs
      inoculated with Actinobacillus pleuropneumoniae.
AB  - OBJECTIVE: To determine the relationship between ambient temperature and mean
      body surface temperature (MBST) measured by use of infrared thermography (IRT)
      and to evaluate the ability of IRT to detect febrile responses in pigs following
      inoculation with Actinobacillus pleuropneumoniae. ANIMALS: 28 crossbred barrows.
      PROCEDURES: Pigs (n = 4) were subjected to ambient temperatures ranging from 10
      to 32 C in an environmental chamber. Infrared thermographs were obtained, and
      regression analysis was used to determine the relationship between ambient
      temperature and MBST. The remaining pigs were assigned to groups in an unbalanced
      randomized complete block design (6 A pleuropneumoniae-inoculated febrile pigs
      [increase in rectal temperature > or = 1.67 C], 6 A pleuropneumoniae-inoculated
      nonfebrile pigs [increase in rectal temperature < 1.67 C], and 12 noninoculated
      pigs). Infrared thermographs and rectal temperatures were obtained for the period
      from 2 hours before to 18 hours after inoculation, and results were analyzed by
      use of repeated-measures ANOVA. RESULTS: A significant linear relationship was
      observed between ambient temperature and MBST (slope, 0.40 C). For inoculated
      febrile pigs, a treatment X method interaction was evident for rectal temperature
      and MBST, whereas inoculated nonfebrile pigs only had increased rectal
      temperatures, compared with noninoculated pigs. A method X time interaction
      resulted from the longer interval after inoculation until detection of an
      increase in MBST by use of IRT. CONCLUSIONS AND CLINICAL RELEVANCE: Infrared
      thermography can be adjusted to account for ambient temperature and used to
      detect changes in MBST and radiant heat production attributable to a febrile
      response in pigs.

PMID- 11341385
TI  - Glucose tolerance testing in llamas and alpacas.
AB  - OBJECTIVE: To determine blood glucose clearance in 2 species of New World
      camelids after IV challenge and to examine mechanisms of this clearance. ANIMALS:
      5 adult female llamas and 5 adult gelded alpacas. PROCEDURE: After food was
      withheld for 12 hours, camelids received 0.5 g of glucose/kg of body weight by
      rapid IV infusion. Serum concentrations of glucose, nonesterified fatty acids,
      cortisol, and insulin, and plasma concentrations of lactate were determined
      before and 0, 1, 2, 3, 4, 5, 15, 30, 60, 90, 120, 180, and 240 minutes after
      infusion. Ratios of insulin to glucose and insulin to cortisol were calculated
      for each time point. RESULTS: Postinfusion glucose concentrations were
      significantly higher in llamas than alpacas for the first 15 minutes and remained
      significantly higher than baseline values in both species for 180 minutes.
      Lactate and cortisol concentrations did not change significantly; nonesterified
      fatty acid concentrations decreased in both species 30 minutes after infusion.
      Baseline insulin concentrations were < 6 microU/ml in both species and increased
      only to 10.1 +/- 0.7 microU/ml in llamas. Insulin concentrations did not change
      significantly in alpacas. CONCLUSIONS AND CLINICAL RELEVANCE: Llamas and alpacas
      clear glucose more slowly than other domestic species after challenge, mainly
      because of a weak insulin response and slow cellular uptake. This response may
      impair the assimilation of exogenous glucose as well as make llamas and alpacas
      prone to diabetes-like disorders when an abundance of endogenous or exogenous
      glucogenic agents are present.

PMID- 11341386
TI  - Inoculation of two genotypes of Hemobartonella felis (California and Ohio
      variants) to induce infection in cats and the response to treatment with
      azithromycin.
AB  - OBJECTIVES: To describe clinical and laboratory findings associated with cats
      experimentally infected by inoculation with the 2 recognized genotypes of
      Hemobartonella felis (small variant, Hfsm; large variant, Hflg) and to determine
      the response of cats to treatment with azithromycin. ANIMALS: 18 young adult
      domestic shorthair cats of both sexes. PROCEDURES: Cats were inoculated with H
      felis and monitored weekly, using CBC counts and a polymerase chain reaction
      (PCR) designed to detect both genetic variants of H felis. Beginning 26 days
      after inoculation, 11 cats were administered azithromycin (15 mg/kg of body
      weight, PO, q 12 h, for 7 days). RESULTS: Inoculation resulted in coinfection
      with Hflg and Hfsm, and both variants were detected by PCR. Clinical
      abnormalities and anemia were most severe in Hflg- and dual-infected cats.
      Results of PCR and CBC were positive for H felis in 112/112 (100%) and 42/112
      (37.5%), respectively, samples collected after inoculation. Administration of
      azithromycin had little effect on clinical variables, including anemia. All cats,
      regardless of treatment with azithromycin, had positive results for the PCR at
      the end of the study period. CONCLUSIONS AND CLINICAL RELEVANCE: In these cats,
      Hflg was more pathogenic than Hfsm, and coinfection with both variants was
      detected. Results of the PCR were superior to results of CBC for detecting
      infection with H felis. Azithromycin administered at the dose and duration
      reported here was not efficacious for the treatment of cats with
      hemobartonellosis.

PMID- 11341387
TI  - Experimental deer-to-deer transmission of Mycobacterium bovis.
AB  - OBJECTIVE: To determine whether Mycobacterium bovis can be transmitted from
      experimentally infected deer to uninfected in-contact deer. ANIMALS: Twenty-three
      6-month-old white-tailed deer. PROCEDURE: On day 0, M bovis (2 X 10(8) colony
      forming units) was administered by intratonsillar instillation to 8 deer; 3
      control deer received saline (0.9% NaCl) solution. Eight in-contact deer were
      comingled with inoculated deer from day 21. On day 120, inoculated deer were
      euthanatized and necropsied. On day 180, 4 in-contact deer were euthanatized, and
      4 new in-contact deer were introduced. On day 360, all in-contact deer were
      euthanatized. Rectal, oral, and nasal swab specimens and samples of hay, pelleted
      feed, water, and feces were collected for bacteriologic culture. Tissue specimens
      were also collected at necropsy for bacteriologic culture and histologic
      analysis. RESULTS: On day 90, inoculated and in-contact deer developed delayed
      type hypersensitivity (DTH) reactions to purified protein derivative of M bovis.
      Similarly, new in-contact deer developed DTH reactions by 100 days of contact
      with original in-contact deer. Tuberculous lesions in in-contact deer were most
      commonly detected in lungs and tracheobronchial and medial retropharyngeal lymph
      nodes. Mycobacterium bovis was isolated from nasal secretions and saliva from
      inoculated and in-contact deer, urine and feces from in-contact deer, and hay and
      pelleted feed. CONCLUSIONS AND CLINICAL RELEVANCE: Mycobacterium bovis is
      efficiently transmitted from experimentally infected deer to uninfected in
      contact deer through nasal secretions, saliva, or contaminated feed. Wildlife
      management practices that result in unnatural gatherings of deer may enhance both
      direct and indirect transmission of M bovis.

PMID- 11341388
TI  - Intranasal vaccination of rabbits with Pasteurella multocida A:3 outer membranes
      that express iron-regulated proteins.
AB  - OBJECTIVE: To determine efficacy of intranasal vaccination of rabbits with
      Pasteurella multocida A:3 outer membrane proteins (OMP) expressing iron-regulated
      OMP (IROMP) in conferring protection against experimental challenge exposure.
      ANIMALS: 52 male New Zealand White rabbits. PROCEDURE: Rabbits were vaccinated
      intranasally on days 0, 7, and 14; some vaccines included cholera toxin (CT) as
      an adjuvant. Concentrations of intranasal IgA and serum IgG antibodies against P
      multocida OMP were determined. In experiment A, rabbits were vaccinated with
      either phospate-buffered saline solution (PBSS), PBSS-CT, OMP-CT, or IROMP-CT,
      challenge-exposed intranasally on day 16, and euthanatized and necropsied on day
      28. Rabbits were also vaccinated with OMP or IROMP without CT and were not
      challenge-exposed. In experiment B, rabbits were vaccinated with PBSS, PBSS-CT,
      IROMP, or IROMP-CT. On day 17, rabbits were challenge-exposed intranasally. Nasal
      bacteria and antibodies were determined on day 24. RESULTS: In experiment A, OMP
      CT vaccination stimulated mucosal and systemic antibody responses to the
      bacterium and enhanced resistance against challenge exposure. Intranasal
      bacterial counts were not significantly reduced. Vaccination with IROMP-CT
      stimulated mucosal and systemic antibodies, enhanced resistance to challenge
      exposure, and significantly reduced nasal bacterial counts. In experiment B,
      natural infection was detected in several rabbits at challenge exposure; however,
      IROMP-CT-vaccinated rabbits had significantly higher serum and nasal antibody
      responses, compared with other rabbits IROMP-CT-vaccinated rabbits had
      significantly lower nasal bacterial counts compared to control rabbits.
      CONCLUSIONS AND CLINICAL RELEVANCE: Intranasal vaccination of rabbits with P
      multocida outer membranes containing IROMP and CT stimulated immunity against
      experimental pneumonic pasteurellosis.

PMID- 11341389
TI  - Effects of enrofloxacin and ciprofloxacin hydrochloride on canine and equine
      chondrocytes in culture.
AB  - OBJECTIVE: To study chondrotoxic effects of enrofloxacin (ENR) and ciprofloxacin
      hydrochloride (CFX) on canine and equine articular chondrocytes in culture and to
      compare the effects with that of cultivation in Mg2+-free medium. SAMPLE
      POPULATION: Chondrocytes from articular cartilage of 4- and 6 -month old dogs and
      2- to 4- year-old horses. PROCEDURE: Chondrocytes were cultivated with 10, 40,
      80, and 160 microg of CFX/ml, 10, 50, 100, and 150 microg of ENR/ml, or in Mg2+
      free medium. A live-to-dead test was performed to test cytotoxic effects.
      Morphologic changes were evaluated by electron microscopy. An attachment assay
      was used to test the ability of chondrocytes to adhere to collagen type-II coated
      chamber slides in the presence of CFX and with Mg2+-free medium. RESULTS:
      Chondrocytes cultivated in quinolone-supplemented medium or Mg2+-free medium had
      a decreased ability to adhere to culture dishes. Cell shape and the actin and
      vimentin cytoskeleton changed in a concentration-dependent manner. These effects
      were not species-specific and developed with both quinolones. On day 1 of
      culture, adhesion of chondrocytes to collagen type II was reduced to 70 and 45%
      of control values in the CFX treatment and Mg2+-free treatment groups,
      respectively. On day 5 of culture, adhesion of chondrocytes was reduced to 45 and
      40% of control values in the CFX treatment and Mg2+-free treatment groups,
      respectively. CONCLUSION AND CLINICAL RELEVANCE: In vitro, chondrotoxic effects
      of quinolones appear to be the result of irregular integrin signaling and
      subsequent cellular changes. Drug concentrations leading to morphologic changes
      in vitro may be achieved in articular cartilage in vivo.

PMID- 11341390
TI  - Effect of topical administration of 2% dorzlamide hydrochloride or 2% dorzlamide
      hydrochloride-0.5% timolol maleate on intraocular pressure in clinically normal
      horses.
AB  - OBJECTIVE: To evaluate the effect of topical administration of 2% dorzolamide
      hydrochloride or 2% dorzolamide hydrochloride-0.5% timolol maleate on intraocular
      pressure (IOP) in clinically normal horses. ANIMALS: 18 healthy adult horses
      without ocular abnormalities. PROCEDURE: The IOP was measured at 5 time points (7
      AM, 9 AM, 11 AM, 3 PM, 7 PM) over 11 days. On days 1 and 2, baseline values were
      established. On days 3 through 5, horses received 2% dorzolamide HCI (group D, n
      = 9) or 2% dorzolamide HCl-0.5% timolol maleate (group DT, 9) in 1 randomly
      assigned eye every 24 hours immediately following each daily 7 AM IOP
      measurement. On days 6 through 9, each drug was given every 12 hours (7 AM and 7
      PM) in the treated eye. Measurements on days 10 and 11 assessed return to
      baseline. Mixed linear regression models compared mean IOP difference for each
      drug at each time period. RESULTS: Mean IOP decreased significantly in all eyes
      during the 2 dose/d period, compared with the baseline, 1 dose/d, and follow-up
      periods. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of either drug every
      24 hours for short-term treatment does not reduce IOP significantly.
      Administering either drug every 12 hours induced a significant reduction of IOP;
      however, controlling for all variables, the reduction was less than 2 mm Hg.

PMID- 11341391
TI  - Expression of interleukin-1beta in the digital laminae of horses in the prodromal
      stage of experimentally induced laminitis.
AB  - OBJECTIVE: To study expression of interleukin-1beta (IL-1beta) in the digital
      laminae of horses in the prodromal stage of experimentally induced laminitis.
      ANIMALS: 8 healthy adult horses with no signs of laminitis. PROCEDURES: Black
      walnut extract was administered via nasogastric tube to 4 horses, and water was
      administered to the remaining 4 (controls). Complete blood counts and physical
      examinations were performed every 30 minutes after administration of black walnut
      extract or water. General anesthesia was induced when total WBC count decreased
      by 30% in horses given the black walnut extract and 3 hours after water
      administration in control horses. The left forefoot was perfusion fixed with
      neutral-buffered 10% formalin, and paraffin-embedded sections of the digit were
      used for in situ hybridization with an equine-specific IL-1beta probe. RESULTS:
      IL-1beta mRNA expression was observed in perivascular cells of the small laminar
      venules and capillaries in all 4 horses given black walnut extract and in
      interstitial cells remote from the microvasculature in 1 of the 4. Other cellular
      components of the laminar tissue and cellular components of the digital
      arterioles and veins did not exhibit IL-1beta mRNA expression. Expression of IL
      1beta mRNA was not detected in laminae from control horses. CONCLUSIONS AND
      CLINICAL RELEVANCE: Results suggest that IL-1beta mRNA is expressed by
      perivascular cells in the laminar tissues of horses in the prodromal stage of
      experimentally induced laminitis. This provides evidence of an inflammatory
      process during the prodromal stage of laminitis, indicating that local digital
      proinflammatory cytokine expression may be an initiating factor in laminitis.

PMID- 11341392
TI  - Biomechanical analysis of suture anchors and suture materials used for toggle pin
      stabilization of hip joint luxation in dogs.
AB  - OBJECTIVE: To compare in vitro mechanical properties of toggle pins and toggle
      rods used as suture anchors and of 3 suture materials (50-lb monofilament
      polybutester, No. 5 braided polyester, and 5-mm woven polyester) commonly used as
      prosthetic ligaments in the repair of hip joint luxation in dogs. SAMPLE
      POPULATION: Femoropelvic specimens from the cadavers of 18 dogs. PROCEDURE:
      Suture anchors were compared by use of pullout tests. Suture materials were
      compared by use of monotonic and cyclic tensile tests; cyclic tensile tests were
      performed with the suture placed over the edge of an aluminum bar to simulate the
      edge of the femoral bone tunnel. In vitro mechanical properties of the ligament
      of the femoral head were determined by use of monotonic tensile tests, using bone
      ligament-bone cadaveric specimens. The in vitro mechanical properties of the
      acetabulum-ligament-femur complex and of this complex following rupture of the
      ligament and stabilization with a toggle rod and 5-mm woven polyester were
      determined by use of compression tests that simulated weight-bearing. RESULTS:
      Mechanical properties of the toggle rod were not significantly different from
      those of the toggle pin. Woven polyester had the longest fatigue life in cyclic
      testing. Hip joints stabilized with a toggle rod and woven polyester had less
      than half the strength in vitro of intact joints. CONCLUSIONS AND CLINICAL
      RELEVANCE: Results suggested that a toggle rod or toggle pin can be used for
      stabilization of hip joint luxations in dogs. Of the materials tested, braided
      polyester had the best in vitro mechanical properties.

PMID- 11341393
TI  - Arthrocentesis of the temporomandibular joint in adult horses.
AB  - OBJECTIVE: To develop a method for arthrocentesis of the temporomandibular joint
      in adult horses. ANIMALS: 7 equine cadaver heads and 6 clinically normal adult
      horses. PROCEDURE: Fluoroscopy, contrast radiography, and computed tomography
      were used on cadaver specimens to locate the temporomandibular joint, identify
      externally palpable landmarks for joint access, guide needle placement into the
      joint, and illustrate regional anatomy. The arthrocentesis technique was
      performed on 6 live healthy adult horses to determine efficacy and safety of this
      procedure. RESULTS: Externally palpable structures were identified as landmarks
      for temporomandibular arthrocentesis, including the lateral border of the
      condylar process of the mandible, the zygomatic process of the temporal bone, and
      the lateral pericapsular fat pad. Arthrocentesis was successful in all 6 joints
      in the live horses, and no complications developed. CONCLUSIONS AND CLINICAL
      RELEVANCE: The technique identified will improve the ability to examine and treat
      the temporomandibular joint in horses.

PMID- 11341394
TI  - Effect of storage conditions on hemostatic parameters of canine plasma obtained
      for transfusion.
AB  - OBJECTIVE: To evaluate the effects of various storage conditions on one-stage
      prothrombin time (OSPT), activated partial thromboplastin time (APTT), and
      fibrinogen concentration of canine plasma collected for transfusion. SAMPLE
      POPULATION: Plasma from 9 dogs. PROCEDURE: Whole blood was collected from dogs by
      means of jugular venipuncture and centrifuged at 7,300 X g for 20 minutes at 0 C.
      A plasma extractor was then used to generate plasma. Aliquots of plasma were
      collected in segments of plastic tubing and in microcentrifuge tubes, and plasma
      collection bags, tubing segments, and microcentrifuge tubes were immediately
      frozen at -30 C. Additional tubing segments and microcentrifuge tubes were stored
      at 2 C. After 1 week of storage, all samples were thawed, and OSPT, APTT, and
      fibrinogen concentration were measured. Collection bags and microcentrifuge tubes
      were refrozen at -30 C, and values were measured again 30 days after blood
      collection. RESULTS: Values for OSPT, APTT, and fibrinogen concentration did not
      vary significantly with storage time, temperature, or container. CONCLUSIONS AND
      CLINICAL RELEVANCE: Results suggested that storage for up to 30 days and at 2 C
      versus -30 C did not have any significant effect on hemostatic parameters of
      canine plasma obtained for transfusion.

PMID- 11341395
TI  - Serologic evaluation, efficacy, and safety of a commerical modified-live canine
      distemper vaccine in domestic ferrets.
AB  - OBJECTIVE: To determine efficacy and safety of a commercial modified-live canine
      distemper virus (CDV) vaccine used for prophylaxis in domestic ferrets. ANIMALS:
      Sixteen 16-week-old neutered male ferrets. PROCEDURES: Equal groups of ferrets
      were inoculated subcutaneously at 16 and 20 weeks of age with saline (0.9% NaCl)
      solution or a vaccine derived from the Onderstepoort CDV strain and attenuated in
      a primate cell line. Live virulent CDV was administered to all ferrets
      intranasally and orally 3 weeks after the second inoculation. Clinical signs and
      body weights were monitored regularly during the study. Blood samples for
      serologic examination were drawn prior to each inoculation, before challenge
      exposure, and 10, 15, and 21 days after exposure. Blood samples for reverse
      transcriptase polymerase chain reaction (RT-PCR) were obtained 5 days after the
      first vaccination, and 5, 10, 15, and 21 days after challenge exposure. RESULTS:
      After challenge exposure, control ferrets had significantly more clinical signs
      and weight loss, compared with vaccinates. All vaccinated ferrets survived,
      whereas all control ferrets died. The RT-PCR assay was successful in detecting
      CDV in blood and fresh or formalin-fixed tissues from infected ferrets.
      CONCLUSIONS AND CLINICAL RELEVANCE: Findings suggest that the vaccine when given
      SC to domestic ferrets as directed is safe and protective against challenge
      exposure with virulent CDV. The RT-PCR assay may simplify detection of CDV in
      fresh and fixed tissues.

PMID- 11341396
TI  - Bovine papillomavirus DNA in neoplastic and nonneoplastic tissues obtained from
      horses with and without sarcoids in the western United States.
AB  - OBJECTIVE: To determine the incidence of bovine papillomavirus (BPV) type 1 or 2
      in sarcoids and other samples of cutaneous tissues collected from horses in the
      western United States. ANIMALS: 55 horses with sarcoids and 12 horses without
      sarcoids. PROCEDURE: Tissue samples (tumor and normal skin from horses with
      sarcoids and normal skin, papillomas, and nonsarcoid cutaneous neoplasms from
      horses without sarcoids) were collected. Tissue samples were analyzed for BPV-1
      or -2 DNA, using a polymerase chain reaction (PCR) and restriction fragment
      length polymorphism. The PCR products from 7 sarcoid-affected horses were
      sequenced to evaluate percentage homology with expected sequences for BPV-1 or-2.
      RESULTS: Most (94/96, 98%) sarcoids contained BPV DNA. Sixty-two percent of the
      tumors examined had restriction enzyme patterns consistent with BPV-2. Thirty-one
      of 49 (63%) samples of normal skin obtained from horses with sarcoids contained
      BPV DNA. All samples subsequently sequenced had 100% homology with the expected
      sequences for the specific viral type. All tissues from healthy horses,
      nonsarcoid neoplasms, and papillomas were negative for BPV DNA. CONCLUSIONS AND
      CLINICAL RELEVANCE: Bovine papillomaviral DNA was detected in essentially all
      sarcoids examined. There appears to be regional variation in the prevalence of
      viral types in these tumors. The fact that we detected viral DNA in normal skin
      samples from horses with sarcoids suggests the possibility of a latent viral
      phase. Viral latency may be 1 explanation for the high rate of recurrence
      following surgical excision of sarcoids.

PMID- 11341397
TI  - Comparison of bending modulus and yield strength between outer stratum medium and
      stratum medium zona alba in equine hooves.
AB  - OBJECTIVE: To determine whether the bending modulus and yield strength of the
      outer stratum medium (SM) differed from those of the SM zona alba (SMZA) and to
      what degree they differed. In addition, a comparison was made among our values
      and values reported elsewhere. SAMPLE POPULATION: 10 normal equine feet.
      PROCEDURE: A 3-point bending technique was used to determine the bending modulus
      and yield strength of the outer SM and SMZA. Efforts were made to minimize
      biological and technical factors that could influence the bending modulus.
      RESULTS: Bending modulus of the outer SM was (mean +/- SD) 187.6 +/- 41.3 MPa,
      whereas mean value for the SMZA was 98.2 +/- 36.8 MPa. Mean yield strength was
      19.4 +/- 2.6 MPa for the outer SM and 5.6 +/- 1.7 MPa for the SMZA. Values for
      bending modulus and yield strength differed significantly between the outer SM
      and SMZA. Significant differences were not detected when the outer SM was loaded
      in bending from the outer or inner surface. CONCLUSIONS AND CLINICAL RELEVANCE:
      Potentially, the SMZA could serve as a mechanical buffer zone between the rigid
      hoof wall and bone and laminar tissues. This buffer zone potentially assists the
      feet of horses in transmitting a load through the tissues and prevents the most
      susceptible tissues from becoming damaged. More consistency among tissue
      selection, preparation, and testing protocols must be attained before an accurate
      3-dimensional finite-element model of an equine foot can be constructed.

PMID- 11341398
TI  - Evaluation of dual energy x-ray absorptiometry for in situ measurement of bone
      mineral density of equine metacarpi.
AB  - OBJECTIVE: To determine the accuracy and precision of dual energy x-ray
      absorptiometry (DEXA) for measuring bone mineral density in horses in situ.
      Sample Population-12 randomly selected forelimbs from 12 horses. PROCEDURE:
      Metacarpi were scanned in 2 planes and DEXA measurements obtained for 6 regions
      of interest (ROI). Each ROI was isolated and bone density measured by Archimedes'
      principle. Linear regression analysis was used to determine the correlation
      between the 2 measurements at each ROI. An additional metacarpus was measured 10
      times to determine the coefficient of variation for both techniques. RESULTS:
      Dual energy x-ray absorptiometry and bone density were significantly associated
      at multiple ROI. The addition of age, weight, and soft tissue or bone thickness
      improved these associations. Repeated measurements had a low coefficient of
      variation. CONCLUSIONS AND CLINICAL RELEVANCE: Dual energy x-ray absorptiometry
      can be used to accurately and precisely measure the bone density in the equine
      metacarpus. Dual energy x-ray absorptiometry appears suitable for serial in vivo
      measurement of bone density of the equine metacarpus. Dual energy x-ray
      absorptiometry may be used for studies to evaluate the effects of diet or drugs
      on bone density or density changes from bone remodeling that develop prior to
      stress fractures.

PMID- 11341399
TI  - Basic three-dimensional kinematics of the vertebral column of horses trotting on
      a treadmill.
AB  - OBJECTIVE: To determine movements of the vertebral column of horses during normal
      locomotion. ANIMALS: 5 young Dutch Warmblood horses that did not have signs of
      back problems or lameness. PROCEDURE: Kinematics of 8 vertebrae (T6, T10, T13,
      T17, L1, L3, L5, and S3) and both tuber coxae were determined, using bone-fixated
      markers. Measurements were recorded when the horses were trotting on a treadmill
      at a constant speed of 4.0 m/s. RESULTS: Flexion-extension and axial rotation
      were characterized by a double sinusoidal pattern of motion during 1 stride
      cycle, whereas lateral bending was characterized by 1 peak and 1 trough. Ranges
      of motion for all vertebrae were: flexion-extension, 2.8 degrees to 4.9 degrees;
      lateral bending, 1.9 degrees to 3.6 degrees; axial rotation, 4.6 to 5.8 degrees,
      except for T10 and T13, where the amount of axial rotation decreased to 3.1
      degrees and 3.3 degrees, respectively. CONCLUSION AND CLINICAL RELEVANCE: During
      locomotion, 3 types of rotations are evident in the thoracolumbar vertebrae.
      Regional differences are observed in the shape and timing of the rotations. These
      differences are related to actions of the limbs. The method described here for
      direct measurement of vertebral column motion provides insights into the complex
      movements of the thoracolumbar portion of the vertebral column in trotting
      horses. Information on normal kinematics is a prerequisite for a better
      understanding of abnormal function of the vertebral column in horses.

PMID- 11341400
TI  - Comparison of heartworm extract-induced shock and endotoxin-induced shock in dogs
      by determination of serum tumor necrosis factor concentrations.
AB  - OBJECTIVE: To compare the mechanisms of heartworm (HW) extract-induced shock and
      endotoxin-induced shock in dogs by determination of serum tumor necrosis factor
      (TNF) concentrations. ANIMALS: 11 mixed-breed dogs (7 without and 4 with HW
      infections). PROCEDURE: Eight dogs were treated with 2 ml of HW extract IV, and 3
      dogs were given endotoxin (Escherichia coli lipopolysaccharide [LPS]) at 40 or
      400 microg/kg of body weight, IV. Changes in clinical and hematologic findings
      and serum TNF concentrations were examined from before treatment to 120 minutes
      after treatment in dogs given HW extract or from before treatment to 180 minutes
      after treatment in dogs given LPS. Tumor necrosis factor concentration was
      determined by cytotoxic assay, using WEHI-164 murine sarcoma cells, and plasma
      endotoxin concentration was determined in 2 dogs treated with HW extract, using
      the endotoxin-specific chromogenic test. RESULTS: Eight dogs developed shock 3 to
      16 minutes after HW extract treatment. Rectal temperature did not change during
      examination. Serum TNF concentration was detected at a low concentration only 60
      and 120 minutes after HW extract treatment, and plasma endotoxin was not detected
      during examination. In dogs treated with LPS, rectal temperature increased to >
      40 C in 2 of 3 dogs, and serum TNF concentration began to increase 30 minutes
      after LPS treatment, reaching a maximum concentration by 60 minutes. CONCLUSIONS:
      The cause and mechanism of HW extract-induced shock may be different from those
      of endotoxin-induced shock, because TNF, which was a pivotal mediator in
      endotoxin-induced shock, increased minimally in serum of dogs treated with HW
      extract.

PMID- 11341401
TI  - Role of histamine in heartworm extract-induced shock in dogs.
AB  - OBJECTIVE: To determine whether heartworm (HW) extract-induced shock in dogs is
      consistent with anaphylactic shock by examining the role of histamine. ANIMALS: 6
      mixed-breed dogs (3 without and 3 with HW infections) and 4 specific pathogen
      free (SPF) Beagles. PROCEDURE: Four experiments were performed as follows: 1) 6
      mixed-breed dogs were treated IV with 2 ml of HW extract, and plasma histamine
      concentrations were determined; 2) 4 SPF dogs were treated IV with 2 ml of HW
      extract and examined for shock; 3) sera from 6 dogs of experiment 1 and from 4
      SPF dogs of experiment 2 that were obtained before HW extract treatment were
      tested for heterologous passive cutaneous anaphylaxis (PCA), using rabbits during
      a sensitization period of 48 to 72 hours; and 4) mast cell degranulation by HW
      extract was tested, using rat mesentery and canine cultured mast cells. RESULTS:
      Experiment 1: 6 dogs developed shock, and plasma histamine concentrations
      increased significantly from 0.3 +/- 0.2 (mean +/- SD) ng/ml before HW extract
      treatment to 44.6 +/- 68.9 ng/ml at the onset of shock; experiment 2: all SPF
      dogs developed shock and had an increase in plasma histamine concentrations;
      experiment 3: sera from mixed-breed dogs without HW infection and from SPF dogs
      had negative PCA reactions; experiment 4: HW extract degranulated rat mesentery
      mast cells and released histamine directly from canine mast cells. CONCLUSIONS
      AND CLINICAL RELEVANCE: Results of our study indicate that an unknown mast cell
      degranulating substances contained in HW extract may degranulate mast cells
      directly, consequently releasing histamine that may participate in the onset of
      shock in HW extract-induced shock in dogs.

PMID- 11341402
TI  - Effect of a tongue-tie on upper airway mechanics in horses during exercise.
AB  - OBJECTIVE: To determine the effect of a tongue-tie on upper airway mechanics in
      exercising horses. ANIMALS: 5 Standardbreds. PROCEDURE: Peak inspiratory and
      expiratory tracheal and pharyngeal pressures and airflow were measured while
      horses exercised on a treadmill with and without a tongue-tie. Respiratory rate
      was also measured. Horses ran at speeds that corresponded to 50 (HR50), 75, 90
      (HR90), and 100% of maximal heart rate. The tongue-tie was applied by pulling the
      tongue forward out of the mouth as far as possible and tying it at the level of
      the base of the frenulum to the mandible with an elastic gauze bandage. Peak
      inspiratory and expiratory tracheal, pharyngeal, and translaryngeal resistance,
      minute ventilation, and tidal volume were calculated. Data were analyzed by use
      of 2-way repeated-measures ANOVA. For post hoc comparison of significant data,
      the Student-Newman-Keuls test was used. RESULTS: We were unable to detect
      significant differences between groups for peak inspiratory or expiratory
      tracheal or pharyngeal resistance, peak pressure, peak expiratory flow, tidal
      volume, respiratory rate, or minute ventilation. Horses that ran with a tongue
      tie had significantly higher peak inspiratory flows, compared with horses that
      ran without a tongue-tie. In the post hoc comparison, this effect was significant
      at 4 m/s, HR50, and HR90. CONCLUSION AND CLINICAL RELEVANCE: Application of a
      tongue-tie did not alter upper respiratory mechanics in exercising horses and may
      be beneficial in exercising horses with certain types of obstructive dysfunction
      of the upper airways. However, application of a tongue-tie does not improve upper
      airway mechanics in clinically normal horses.

PMID- 11341403
TI  - Effect of a tongue-tie on upper airway mechanics during exercise following
      sternothyrohyoid myectomy in clinically normal horses.
AB  - OBJECTIVE: To determine the effect of a tongue-tie on upper airway mechanics in
      clinically normal horses exercising on a treadmill following sternothyrohyoid
      myectomy. ANIMALS: 6 Standardbreds. PROCEDURE: Upper airway mechanics were
      measured with horses exercising on a treadmill at 5, 8, and 10 m/s 4 weeks after
      a sternothyrohyoid myectomy was performed. Pharyngeal and tracheal inspiratory
      and expiratory pressures were measured by use of transnasal pharyngeal and
      tracheal catheters connected to differential pressure transducers. Horses were
      fitted with a facemask and airflow was measured by use of a pneumotachograph.
      Horses underwent a standardized exercise protocol on a treadmill at 5, 8, and 10
      m/s with and without a tongue-tie in a randomized cross-over design. Inspiratory
      and expiratory airflow, tracheal pressure, and pharyngeal pressure were measured,
      and inspiratory and expiratory resistances were calculated. RESULTS: We were
      unable to detect an effect of a tongue-tie on any of the respiratory variables
      measured. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicate that a tongue-tie
      does not alter upper airway mechanics following sternothyrohyoid myectomy in
      clinically normal horses during exercise.

PMID- 11341404
TI  - Pharmacokinetics of imipramine in narcoleptic horses.
AB  - OBJECTIVE: To validate use of high-performance liquid chromatography (HPLC) in
      determining imipramine concentrations in equine serum and to determine
      pharmacokinetics of imipramine in narcoleptic horses. ANIMALS: 5 horses with
      adult-onset narcolepsy. PROCEDURE: Blood samples were collected before (time 0)
      and 3, 5, 10, 15, 20, 30, and 45 minutes and 1, 2, 3, 4, 6, 8, 12, and 24 hours
      after IV administration of imipramine hydrochloride (2 or 4 mg/kg of body
      weight). Serum was analyzed, using HPLC, to determine imipramine concentration.
      The serum concentration-versus-time curve for each horse was analyzed separately
      to estimate pharmacokinetic values. RESULTS: Adverse effects (muscle
      fasciculations, tachycardia, hyperresponsiveness to sound, and hemolysis) were
      detected in most horses when serum imipramine concentrations were high, and these
      effects were most severe in horses receiving 4 mg of imipramine/kg. Residual
      adverse effects were not apparent. Value (mean +/- SD) for area under the curve
      was 3.9 +/- 0.7 h X microg/ml, whereas volume of distribution was 584 +/- 161.7
      ml/kg, total body clearance was 522 +/- 102 ml/kg/h, and mean residence time was
      1.8 +/- 0.6 hours. One horse had signs of narcolepsy 6 and 12 hours after
      imipramine administration; corrresponding serum imipramine concentrations were
      less than the therapeutic range. CONCLUSIONS AND CLINICAL RELEVANCE: Potentially
      serious adverse effects may be seen in horses administered doses of imipramine
      that exceed a dosage of 2 mg/kg. Total body clearance of imipramine in horses is
      slower than that in humans; thus, the interval between subsequent doses should be
      longer in horses.

PMID- 11341405
TI  - Site-specific adaptive remodeling of Greyhound metacarpal cortical bone subjected
      to asymmetrical cyclic loading.
AB  - OBJECTIVE: To quantify geometric, inertial, and histomorphometric properties at
      the mid-diaphyseal level of left and right metacarpal bones (MCB) of racing
      Greyhounds. SAMPLE POPULATION: MCB from 7 racing Greyhounds euthanatized for
      reasons unrelated to MCB abnormalities. PROCEDURES: Mid-diaphyseal transverse
      sections of left and right MCB were stained with H&E or microradiographed. Images
      of stained sections were digitized, and cross-sectional area, cortical area, and
      maximum and minimum area moments of inertia of each bone were determined.
      Histomorphometric data (osteonal density, osteonal birefringence, and endosteal
      new lamellar bone thickness) were collected in 4 quadrants (dorsal, palmar,
      lateral, medial). Values were compared between limbs and among bones and
      quadrants. RESULTS: Cross-sectional area, cortical area, and maximum and minimum
      moments of inertia of left MCB-IV and -V were significantly greater, compared
      with contralateral bones. Overall osteonal densities in the dorsal quadrants of
      left MCB were greater, compared with lateral and medial quadrants. Also,
      percentage of birefringent osteons was significantly greater in the dorsal
      quadrant of left MCB-III, -IV, and -V, compared with the palmar quadrant.
      Thickness of new endosteal lamellar bone was not significantly influenced by
      limb, bone, or quadrant. CONCLUSIONS AND CLINICAL RELEVANCE: Increased cortical
      thickness and geometric properties of left MCB-IV and -V of Greyhounds, together
      with altered turnover and orientation of osteons in the dorsal quadrants of left
      MCB, are site-specific adaptive responses associated with asymmetric cyclic
      loading as a result of racing on circular tracks. Site-specific adaptive
      remodeling may be important in the etiopathogenesis of fatigue fractures in
      racing Greyhounds.

PMID- 11341406
TI  - Effects of long-term administration of recombinant bovine tumor necrosis factor
      alpha on glucose metabolism and growth hormone secretion in steers.
AB  - OBJECTIVE: To investigate the effects of long-term administration of recombinant
      bovine tumor necrosis factor-alpha (rbTNF) on plasma glucose and growth hormone
      concentrations, and to determine whether treatment with rbTNF causes insulin
      resistance in steers. ANIMALS: 5 steers treated with rbTNF and 5 steers treated
      with saline (0.9% NaCl) solution (control). PROCEDURES: In experiment 1, rbTNF
      (5.0 microg/kg of body weight) or saline solution (5 ml) was administered SC
      daily for 12 days. Blood samples were obtained before treatment, and plasma was
      harvested for determination of glucose, insulin, and growth hormone (GH)
      concentrations. In experiment 2, insulin, glucose, or growth hormone-releasing
      hormone (GHRH) was administered IV on days 7, 9, and 11, respectively, after
      initiation of rbTNF or saline treatment in experiment 1. Plasma glucose and
      insulin concentrations were measured before and at various times for 4 hours
      after insulin or glucose administration. Plasma GH concentrations were measured
      at various times for 3 hours after GHRH administration. RESULTS: In experiment 1,
      administration of rbTNF resulted in hyperinsulinemia without hypoglycemia and
      decreased plasma GH concentrations. In experiment 2, plasma glucose
      concentrations were higher in steers treated with rbTNF and insulin than in
      controls. Plasma GH concentrations were lower in steers treated with rbTNF and
      GHRH than in controls. CONCLUSIONS AND CLINICAL RELEVANCE: Prolonged treatment
      with rbTNF induced insulin resistance and inhibited GHRH-stimulated release of GH
      in steers. Results indicate that rbTNF is a proximal mediator of insulin
      resistance and inhibits release of GH during periods of endotoxemia or infection.

PMID- 11341407
TI  - Blood oxygen binding in calves with naturally occurring diarrhea.
AB  - OBJECTIVE: To assess blood oxygen binding in calves with diarrhea. ANIMALS: 22
      dairy and 26 double-muscled calves with diarrhea, 31 healthy dairy calves and 37
      healthy double-muscled calves. PROCEDURE: Severity of disease, including the
      ability of affected calves to stand, was evaluated. Hydration and signs of
      depression were scored. Venous and arterial blood samples were collected, and 2,3
      diphosphoglycerate, ATP, chloride, inorganic phosphate, lactate, pyruvate, total
      protein, albumin, and hemoglobin concentrations, and Hct, pH, Pco2, and PO2 were
      determined. Oxygen equilibrium curves (OEC) were constructed under standard
      conditions, and oxygen extraction ratios were calculated. RESULTS: Recumbent
      calves of both breed-types were more dehydrated and had more severe signs of
      depression than ambulatory affected calves. In both breed-types, hemoglobin
      oxygen affinity was increased in calves with diarrhea, compared with healthy
      calves, as indicated by a decrease in standard partial oxygen pressure (P50).
      Diarrhea induced hypocapnia and hypothermia in the most severely affected calves,
      which counteracted the acidosis-induced right shift in arterial and venous OEC.
      Arterial and venous P50 were significantly less in double-muscled calves with
      diarrhea than healthy calves, whereas P50 for affected dairy calves were similar
      to those of healthy calves. Except in the most severely affected dairy calves,
      oxygen extraction ratio was significantly less in calves with diarrhea, compared
      with healthy calves. CONCLUSIONS AND CLINICAL RELEVANCE: Release of oxygen from
      blood may be impaired in calves with diarrhea, depending on the effect of the
      disease on certain blood biochemical variables.

PMID- 11341408
TI  - Development of an ex vivo model to study adherence of Mannheimia haemolytica
      serovar 1 to mucosal tissues of the respiratory tract of cattle.
AB  - OBJECTIVE: To develop and validate an ex vivo model for study of adherence of
      Mannheimia haemolytica (formerly Pasteurella haemolytica) to respiratory tract
      mucosa of cattle and to use this model to confirm adherence of M haemolytica
      serovar 1 (Mh1) to several relevant respiratory mucosal surfaces. SAMPLE
      POPULATION: Excised nasal, nasopharyngeal, turbinate, and tonsillar mucosal
      tissue from the bovine upper respiratory tract. PROCEDURE: Mh1 was radiolabeled
      by use of tritiated leucine. Various concentrations of labeled bacteria were
      incubated with bovine upper respiratory tract tissues for various times. Tissue
      was washed to remove nonadherent bacteria, and percentage of bacteria adhered
      (percentage of adherence) was estimated using radioactivity. Using an optimal
      inoculum concentration and incubation time, percentage of Mh1 adherence was
      compared on nasal, nasopharyngeal, turbinate, and tonsillar mucosal tissue, and
      adherence to nasopharyngeal tissue was confirmed by scanning and transmission
      electron microscopy. RESULTS: The optimal Mh1 inoculum concentration was 1 X
      10(7) colony forming units/ml and incubation time was 3 hours. Percentage of
      adherence of Mh1 to nasopharyngeal tissue was greater than adherence to other
      tissue types. CONCLUSIONS AND CLINICAL RELEVANCE: The ex vivo model maintained
      the functional and structural integrity of bovine upper respiratory tract mucosa,
      as confirmed by light and electron microscopy. Electron microscopy revealed
      participation of epithelial cell cilia and surface mucus in adherence of Mh1 to
      nasopharyngeal tissue. Adherence of Mh1 was confirmed in repeated assays,
      indicating that this organism adheres to upper respiratory tract mucosa of
      cattle.

PMID- 11341410
TI  - Outcomes evaluation in orthopaedics.

PMID- 11341409
TI  - Development of the refractive state in eyes of ostrich chicks (Struthio camelus).
AB  - OBJECTIVE: To follow the development of the refractive error in the eyes of
      ostrich chicks from age 0 to day 37 after hatching. ANIMALS: 35 ostrich chicks.
      PROCEDURES: Spot retinoscopy was conducted to assess refractive error in ostrich
      chicks. Seventy eyes of 35 ostrich chicks were examined. Of these, 18 chicks were
      followed over time. At least 4 serial measurements (at 2- to 7- day intervals)
      were conducted in each of these chicks from day 1 to 37 after hatching. Seventeen
      additional chicks were examined on days 0, 3, 12, and 19 after hatching. RESULTS:
      Ostrich chicks were myopic at hatching, with a mean +/- SD refractive error of 
      4.47 +/- 0.15 diopters (D). The refractive error rapidly decreased during the
      first week of life, and by day 7 after hatching, chicks were slightly hyperopic,
      with a mean refractive error of 0.42 +/- 0.12 D. After day 7, there were no
      significant differences in the mean refractive error. CONCLUSIONS: The
      development of optics in the ostrich eye appears to be unique among animals and
      is characterized by myopia at hatching, rapid onset of emmetropia, and minimal
      variation in refractive error among chicks.

PMID- 11341412
TI  - Long-term review of the lumbar spine in javelin throwers.
AB  - We studied 21 former top-class competitive javelin throwers to investigate
      radiological and clinical symptoms in the lumbar spine many years after the end
      of their athletic careers. The athletes underwent clinical and radiological
      examinations at an average of 20 years after retiring from athletics. The
      Hannover questionnaire was used to evaluate functional restrictions in daily
      living. Degenerative changes in the lumbar spine were more marked towards the
      caudal aspect of the spine. Ten athletes also had spondylolisthesis, but with
      little progression (< 15%) throughout the observation period. Athletes both with
      and without radiologically demonstrated spondylolisthesis, complained of no more
      back problems than the normal population (93% for athletes v 86% for controls).
      Slight progression followed their retirement from athletics.

PMID- 11341411
TI  - The management of osteoporosis.
AB  - Osteoporosis poses a significant orthopaedic problem of epidemic proportions.
      Clear guidelines for the management of osteoporosis presenting early or late are
      still being debated. Several recommendations, however, are now generally
      accepted. Measurements of BMD should be taken if the diagnosis is in doubt or as
      an adjunct to encourage patient compliance with treatment. Those with multiple
      risk factors and who are under the age of 65 years would benefit from a scan.
      Those with previous fractures and no obvious risk factors should also be sent for
      DXA assessment. The elderly with fractures and multiple risk factors do not need
      scanning and can normally be started on treatment. Mass population screening is
      not cost-effective. Prevention strategies should be targeted at high-risk
      patients and not offered to everyone. In the perimenopausal woman HRT is the
      first line of treatment and prevention, along with changes in lifestyle. Tibolone
      may be an option for those who find cyclical bleeding unacceptable. In the
      elderly, institutionalised patient, calcium and vitamin-D supplements should be
      considered to replace depleted levels, particularly for secondary prevention.
      Postmenopausal women with multiple risk factors and at least one insufficiency
      fracture should be treated. The most likely pharmacological agent will be a
      bisphosphonate with supplemental calcium if indicated. Each hospital should have
      a recognised link person through whom referrals can be channelled, either a
      clinical nurse specialist or physician. A protocol for treatment should be agreed
      locally and publicised among the primary health-care groups. The first step of
      identification of high-risk patients is most often in fracture clinics.
      Standardised letters attached to the clinic note to general practitioners are an
      easy way of 'getting these patients into the system'.

PMID- 11341413
TI  - Stenosis of the cervical canal in craniodiaphyseal dysplasia.
AB  - Craniodiaphyseal dysplasia (CDD) is a rare sclerosing bone disorder, the severity
      of which depends on its phenotypic expression. Hyperostosis can cause progressive
      foraminal stenosis leading to palsy of cranial nerves, epilepsy and mental
      retardation. We report the only case of CDD in an adult, with stenosis of the
      cervical canal leading to quadriparesis as a late complication of hyperostosis,
      and describe the problems associated with its treatment. Although the syndrome is
      rare, its pathophysiological and therapeutic considerations may be applicable to
      the management of stenosis of the spinal canal in other hyperostotic bone
      disorders.

PMID- 11341414
TI  - Radiation therapy for the prevention of heterotopic ossification at the elbow.
AB  - We present nine patients (five men and four women) who underwent surgical
      excision of clinically significant heterotopic ossification at the elbow. They
      also received perioperative radiation therapy using total doses between 600 and
      1000 cGy. Five received fractionated radiotherapy, with two fractions of 500 cGy
      applied on the first two postoperative days, and the remaining four were
      irradiated with single doses of 600 and 700 cGy. After a mean period of
      observation of 7.7 months (6 to 13) none had radiological recurrence of
      heterotopic ossification and eight showed clinical improvement. Assessment of the
      functional outcome showed a mean improvement in the Morrey score from 33.3 to
      84.5 points indicating a high therapeutic efficacy of prophylactic irradiation.

PMID- 11341415
TI  - Selective lengthening of the proximal flexor tendon in the management of acquired
      claw toes.
AB  - We report the management of the acquired claw-toe deformity in ten adults. Each
      patient developed a varying number of claw toes at a mean interval of six months
      after the time of injury. There was clinical evidence of an acute compartment
      syndrome in one case. The clawing occurred at the start of heel-rise in the
      stance phase of gait. At this stage the patients complained of increasing pain
      and pressure on the tips of the toes. The deformities were corrected by
      lengthening flexor hallucis longus and flexor digitorum longus alone or in
      combination. The presence of variable intertendinous digitations between the
      tendons of flexor hallucis longus and flexor digitorum longus means that in some
      cases release of flexor hallucis longus alone may correct clawing of lesser toes.

PMID- 11341416
TI  - Appropriate questionnaires for knee arthroplasty. Results of a survey of 3600
      patients from The Swedish Knee Arthroplasty Registry.
AB  - The Swedish Knee Arthroplasty Registry (SKAR) has recorded knee arthroplasties
      prospectively in Sweden since 1975. The only outcome measure available to date
      has been revision status. While questionnaires on health outcome may function as
      more comprehensive endpoints, it is unclear which are the most appropriate. We
      tested various outcome questionnaires in order to determine which is the best for
      patients who have had knee arthroplasty as applied in a cross-sectional,
      discriminative, postal survey. Four general health questionnaires (NHP, SF-12, SF
      36 and SIP) and three disease/site-specific questionnaires (Lequesne, Oxford-12,
      and WOMAC) were tested on 3600 patients randomly selected from the SKAR.
      Differences were found between questionnaires in response rate, time required for
      completion, the need for assistance, the efficiency of completion, the validity
      of the content and the reliability. The mean overall ranks for each questionnaire
      were generated. The SF-12 ranked the best for the general health, and the Oxford
      12 for the disease/site-specific questionnaires. These two questionnaires could
      therefore be recommended as the most appropriate for use with a large knee
      arthroplasty database in a cross-sectional population.

PMID- 11341417
TI  - Specificity of the Oxford knee status questionnaire. The effect of disease of the
      hip or lumbar spine on patients' perception of knee disability.
AB  - There is a need for the accurate measurement of the outcome after knee surgery.
      The Oxford Knee Score is being increasingly used since it is reported to be
      short, simple, inexpensive and validated. We sent the questionnaire to 346
      patients awaiting surgery to the hip or lumbar spine. Only 11% of 141 patients
      with proximal pathology who denied knee problems gave a maximum score. Their mean
      score was substantially lower than expected at 28.7 (maximum 48), and was
      significantly lower than the score of 36.5 obtained from patients after total
      knee replacement. We therefore suggest that the frequent coexistence of hip or
      spinal pathology will significantly alter both the absolute score and any
      improvement to be expected after knee surgery. Although sensitive to disability
      originating from the knee the Oxford Knee Score is not sufficiently specific
      since it is heavily influenced by more proximal pathology.

PMID- 11341418
TI  - A comparison of quadruple semitendinosus and patellar tendon grafts in
      reconstruction of the anterior cruciate ligament.
AB  - In a two-centre study, 164 patients with unilateral instability of the anterior
      cruciate ligament were prospectively randomised to arthroscopic reconstruction
      with either a patellar tendon graft using interference screw fixation or a
      quadruple semitendinosus graft using an endobutton fixation technique. The same
      postoperative rehabilitation protocol was used for all patients and follow-up at
      a median of 31 months (24 to 59) was carried out by independent observers. Four
      patients (2%) were lost to follow-up. No significant differences were found
      between the groups regarding the Stryker laxity test, one-leg hop test, Tegner
      activity level, Lysholm score, patellofemoral pain score, International Knee
      Documentation Committee (IKDC) score or visual analogue scale, reflecting patient
      satisfaction and knee function. Slightly decreased extension, compared with the
      non-operated side, was found in the patellar tendon group (p < 0.05). Patients
      with associated meniscal injuries had lower IKDC, visual analogue (p < 0.01) and
      Lysholm scores (p < 0.05) than those without such injuries. Patients in whom
      reconstruction had been carried out less than five months after the injury had
      better final IKDC scores than the more chronic cases (p < 0.05). We conclude that
      patellar tendon and quadruple semitendinous tendon grafts have similar outcomes
      in the medium term. Associated meniscal pathology significantly affects the final
      outcome and early reconstruction seems to be beneficial.

PMID- 11341419
TI  - Long-term results of Kinematic Condylar knee replacement. An analysis of 404
      knees.
AB  - We present the long-term results of the Kinematic Condylar Knee Arthroplasty
      followed in a prospective fashion. Between October 1982 and March 1988, 404
      consecutive replacement arthroplasties were carried out on 335 patients. Of
      these, 354 knees had osteoarthritis, 45 rheumatoid arthritis and five other
      diagnoses. At the time of final follow-up 158 patients (188 knees) had died. No
      patient was lost to follow-up. The minimum follow-up for all living patients was
      ten years (10 to 17). The mean age at surgery was 68 years (30 to 92). There were
      seven complications (1.7%). Sixteen knees (3.9%) were revised, four because of
      infection. Survivorship was 99.4% (CI 97.9 to 99.8) at five years, 98.2% (CI 96.1
      to 99.2) at ten years and 92.6% (CI 87.6 to 95.6) at 17 years.

PMID- 11341420
TI  - The Kinemax total knee arthroplasty. Nine years' experience.
AB  - We reviewed the outcome of 422 primary cemented Kinemax total knee arthroplasties
      implanted into 369 patients over a period of five years, from January 1989. The
      operations were carried out at two NHS district general hospitals and one
      teaching hospital by 31 surgeons. During the period of review, 49 patients died
      and ten knees were lost to follow-up (68 knees). The mean Knee Society score
      improved from 28 before to 89 after surgery, and the mean function score
      increased from 23 to 79. The range of flexion improved from 92 degrees to 105
      degrees. These improvements were maintained throughout the period of study. At
      the latest review radiolucent lines of 1 mm were seen around 15% of tibial
      components, 1.4% of patellar components and 9.5% of femoral components. In no
      case were these changes progressive. Using revision as the endpoint, cumulative
      survival was 99% after five years and 96.95% after nine years. All revisions were
      undertaken for deep infection or secondary trauma. Our study has shown that the
      Kinemax total knee replacement, when carried out with retention of the posterior
      cruciate ligament by surgeons of varying experience, produces very satisfactory
      results in the medium term.

PMID- 11341421
TI  - Isolated calf lengthening in cerebral palsy. Outcome analysis of risk factors.
AB  - We assessed the medium-term outcome of three methods of isolated calf lengthening
      in cerebral palsy by clinical examination, observational gait analysis and, where
      appropriate, instrumented gait analysis. The procedures used were percutaneous
      lengthening of tendo Achillis, open Z-lengthening of tendo Achillis and
      lengthening of the gastrosoleus aponeurosis (Baker's procedure). We reviewed 195
      procedures in 134 children; 45 had hemiplegia, 65 diplegia and 24 quadriplegia.
      We established the incidence of calcaneus and recurrent equinus and identified
      'at-risk' groups for each. At follow-up, 42% had satisfactory calf length, 22%
      had recurrent equinus and 36% calcaneus. The incidence of calcaneus in girls at
      follow-up was significantly higher (p = 0.002) while boys had an increased rate
      of recurrent equinus (p = 0.012). Children with diplegia who had surgery when
      aged eight years or younger had a 44% risk of calcaneus, while those over eight
      years had a 19% risk (p = 0.046). Percutaneous lengthening of tendo Achillis in
      diplegia was the least predictable, only 38% having a satisfactory outcome
      compared with 50% in the other procedures. The incidence of recurrent equinus in
      hemiplegic patients was 38%. Only 4% developed calcaneus. The type of surgery did
      not influence the outcome in patients with hemiplegia or quadriplegia. Severity
      of involvement, female gender, age at operation of less than eight years and
      percutaneous lengthening of tendo Achillis were 'risk factors' for calcaneus.
      Hemiplegia, male gender, and an aponeurosis muscle lengthening increased the risk
      of recurrent equinus.

PMID- 11341422
TI  - Natural history of scoliosis in children with syringomyelia.
AB  - We performed a retrospective review of 27 scoliotic patients with syringomyelia
      using MRI. Their mean age at the first MRI examination was 10.9 years, and at the
      final review 15.8 years. The mean ratio of the diameter of the syrinx to the cord
      on the midsagittal MRI (S/C ratio) decreased from 0.49 to 0.24; 14 patients
      showed a decrease of 50% or more (reduction group). In this reduction group, the
      cerebellar tonsillar herniation decreased from a mean of 11.3 mm to 6.0 mm, and
      some improvement in dissociated sensory disturbance was seen in nine of 13
      patients. The scoliosis improved by 5 degrees or more in six patients in the
      reduction group. Our results indicate that spontaneous shrinkage of syringomyelia
      in children is not unusual and is associated with improvement in the tonsillar
      herniation, the scoliosis and the neurological deficit.

PMID- 11341423
TI  - Microanatomy of the acetabular cavity and its relation to growth.
AB  - The anatomy and development of the growing acetabulum are not clearly understood.
      We dissected and studied histologically two acetabula from the pelvis of a three
      month-old infant. Relative rates of growth at the different growth plates were
      assessed by comparing the height of the proliferative layer with that of the
      hypertrophic layer. The three bones which form the acetabulum are surrounded by
      growth plates on all sides except medially. These face towards the centre of the
      triradiate cartilage, the limbs of the triradiate cartilage and the articular
      surface and each may be divided into four distinct areas according to the
      orientation of its cell columns which reflect the direction of growth. Growth was
      particularly rapid at the ischial growth plates directed towards the centre and
      the articular cartilage, add on both sides of the anterior limb of the triradiate
      cartilage. These findings may explain the mechanism by which the acetabulum
      changes orientation and inclination with growth.

PMID- 11341424
TI  - Talectomy in patients with recurrent deformity in club foot. A long-term follow
      up study.
AB  - We reviewed 24 feet in 15 patients who had undergone talectomy for recurrent
      equinovarus deformity; 21 were associated with arthrogryposis multiplex
      congenita, two with myelomeningocele and one with idiopathic congenital talipes
      equinovarus. The mean follow-up was 20 years. Good results were achieved in eight
      feet (33%) in which further surgery was not needed and walking was painless; a
      fair result was obtained in ten feet (42%) in which further surgery for
      recurrence of a hindfoot deformity had been necessary but walking was painless;
      the remaining six feet (25%) were poor, with pain on walking. All patients wore
      normal shoes and could walk independently, except one who was wheelchair-bound
      because of other joint problems. Recurrent deformity, the development of
      tibiocalcaneal arthritis and spontaneous fusion of the tibia to the calcaneum
      were all seen in these patients.

PMID- 11341425
TI  - Anxiety reaction in children during removal of their plaster cast with a saw.
AB  - We have had experience of an 18-month-old boy with a cardiomyopathy who died a
      few minutes after removal of his cast with a saw, apparently from a malignant
      cardiac arrhythmia triggered by anxiety. We therefore examined the anxiety
      reaction to this method of removal of a plaster cast in 20 healthy children; ten
      were provided with hearing protectors and ten were not. The level of anxiety was
      assessed by measuring the heart rate, a known physiological indicator of anxiety,
      before, during and five minutes after removal of the cast. The noise level was
      also measured. The results showed a mean increase in heart rate during the
      procedure of 27.9 beats per minute (bpm) (26.9%) in the children with no hearing
      protectors and 10.4 bpm (11.1%) in children who used hearing protectors (p <
      0.001). Five minutes after the procedure the heart rate had returned to the
      baseline rate in all patients. We recommend that hearing protectors should be
      used in children undergoing removal of a plaster cast to decrease the anxiety
      reaction. If possible, clinicians should avoid the use of a saw for this purpose
      in children with a cardiomyopathy.

PMID- 11341426
TI  - Percutaneous radiofrequency ablation in osteoid osteoma.
AB  - We treated 58 patients with osteoid osteoma by CT-guided radiofrequency ablation
      (RF). In 16 it followed one or two unsuccessful open procedures. It was performed
      under general anaesthesia in 48, and spinal anaesthesia in ten. The nidus was
      first located by thin-cut CT (2 to 3 mm) sections. In hard bony areas a 2 mm
      coaxial drill system was applied. In softer areas an 11-gauge Jamshidi needle was
      inserted to allow the passage of a 1 mm RF probe into the centre of the nidus. RF
      ablation was administered at 90 degrees C for a period of four to five minutes.
      Three patients had recurrence of pain three, five and seven months after
      treatment, respectively, and a second percutaneous procedure was successful.
      Thus, the primary rate of success for all patients was 95% and the secondary rate
      was 100%. One minor complication was encountered. CT-guided RF ablation is a
      safe, simple and effective method of treatment for osteoid osteoma.

PMID- 11341427
TI  - Sample size and statistical power of randomised, controlled trials in
      orthopaedics.
AB  - We reviewed all 717 manuscripts published in the 1997 issues of the British and
      American volumes of the Journal of Bone and Joint Surgery and in Clinical
      Orthopaedics and Related Research, from which 33 randomised, controlled trials
      were identified. The results and sample sizes were used to calculate the
      statistical power of the study to distinguish small (0.2 of standard deviation),
      medium (0.5 of standard deviation), and large (0.8 of standard deviation) effect
      sizes. Of the 33 manuscripts analysed, only three studies (9%) described
      calculations of sample size. To perform post-hoc power assessments and
      estimations of deficiencies of sample size, the standard effect sizes of Cohen
      (small, medium and large) were calculated. Of the 25 studies which reported
      negative results, none had adequate power (beta < 0.2) to detect a small effect
      size and 12 (48%) lacked the power necessary to detect a large effect size. Of
      the 25 studies which did not have an adequate size of sample to detect small
      differences, the average used was only 10% of the required number Our findings
      suggest that randomised, controlled trials in clinical orthopaedic research
      utilise sample sizes which are too small to ensure statistical significance for
      what may be clinically important results.

PMID- 11341428
TI  - Chronic osteomyelitis. The effect of the extent of surgical resection on
      infection-free survival.
AB  - We studied prospectively a consecutive series of 50 patients with chronic
      osteomyelitis. Patients were allocated to the following treatment groups: 1) wide
      resection, with a clearance margin of 5 mm or more; 2) marginal resection, with a
      clearance margin of less than 5 mm; and 3) intralesional biopsy, with debulking
      of the infected area. All patients had a course of antibiotics, intravenously for
      six weeks followed by orally for a further six weeks. No patients in group 1 had
      recurrence. In patients treated by marginal resection (group 2), 8 of 29 (28%)
      had recurrence. All patients who had debulking had a recurrence within one year
      of surgery. We performed a survival analysis to determine the time of the
      recurrence of infection. In group 2 there was a higher rate of recurrence in type
      B hosts (p < 0.05); no type-A hosts had recurrence. This information is of use in
      planning surgery for chronic osteomyelitis.

PMID- 11341429
TI  - Survival analysis of cementless grit-blasted titanium total hip arthroplasties.
AB  - Although about 200000 cementless Zweymuller-Alloclassic total hip arthroplasties
      (THAs) were carried out worldwide in the last decade, the survival analysis of
      these prostheses was not available in the 2000 report of the Swedish national hip
      arthroplasty registry. We report a prospective survivorship analysis of 200
      consecutive grit-blasted cementless Alloclassic primary THAs carried out since
      1988. Using surgical, clinical and radiological endpoints for the stem and the
      threaded cup the ten-year survivorship was 91.5% for reoperation for any cause,
      96.4% for hip pain (Merle d'Aubigne score < 5 points, clinical failure), 99.4%
      for definite aseptic loosening (radiological failure) and 99.3% for revision for
      aseptic loosening. Using the Swedish registry criteria of primary osteoarthritis
      and revision for aseptic loosening as the endpoint, the survival rate of 99.1% at
      ten years for the subgroup of 157 Alloclassic THAs in osteoarthritis compares
      favourably with that of the best modern cemented hip replacements reported in the
      Swedish arthroplasty registry.

PMID- 11341430
TI  - Cardiac output during hemiarthroplasty of the hip. A prospective, controlled
      trial of cemented and uncemented prostheses.
AB  - In a prospective, controlled study, we measured the effect on cardiac output of
      the introduction of methylmethacrylate during hemiarthroplasty for displaced
      fractures of the femoral neck. We treated 20 elderly patients who were similar in
      age, height, weight and preoperative left ventricular function with either
      cemented or uncemented hemiarthroplasty. Using a transoesophageal Doppler probe,
      we measured cardiac output before incision and at six stages of the procedure:
      during the surgical approach, reaming and lavage of the femoral canal, the
      introduction of cement, the insertion of the prosthesis, and in reduction and
      closure. We found that before the cement was introduced, there was no difference
      in stroke volume or cardiac output (p > 0.25). Cementation produced a transient
      but significant reduction in cardiac output of 33% (p < 0.01) and a reduction in
      stroke volume of 44% (p < 0.02). The introduction of cement did not affect the
      heart rate or mean arterial pressure. There was no significant difference in
      cardiac function on insertion of the prosthesis. Standard non-invasive
      haemodynamic monitoring did not detect the cardiovascular changes which may
      account for the sudden deaths that sometimes occur during cemented
      hemiarthroplasty. The fall in stroke volume and cardiac output may be caused by
      embolism occurring during cementation, but there was no similar fall during
      reaming or insertion of the prosthesis.

PMID- 11341431
TI  - The extent of osteocyte death in the proximal femur of patients with
      osteonecrosis of the femoral head.
AB  - Our aim was to assess the local extent of osteocyte death in the proximal femur
      of 16 patients with osteonecrosis of the femoral head. We performed histological
      examination of the femoral heads and cancellous bone biopsies from four regions
      of the proximal femur in patients undergoing total hip arthroplasty. A control
      group consisted of 19 patients with osteoarthritis. All histological specimens
      were examined in a blinded fashion. Extensive osteonecrosis was shown in the
      proximal femur up to 4 cm below the lesser trochanter in the group with
      osteonecrosis. There was an overall statistically significant difference in the
      extent of osteocyte death distal to the femoral head between the two groups (p <
      0.001). We discuss the implications of these findings as possible contributing
      factors in regard to the early failure of total hip arthroplasty reported in
      patients with osteonecrosis of the femoral head.

PMID- 11341432
TI  - Fractures involving splitting of the humeral head.
AB  - Splitting fractures of the humeral head are rare; part of the humeral head
      dislocates and the unfractured part remains attached to the shaft. We report
      eight cases in young patients. In five the diagnosis was made at presentation:
      three had minimal internal fixation using a superior subacromial approach, one
      had a closed reduction and one a primary prosthetic replacement. All five
      patients regained excellent function with no avascular necrosis at two years. In
      three the injury was initially unrecognised; two developed a painless bony
      ankylosis and one is awaiting hemiarthroplasty. It is important to obtain the
      three trauma radiographic views to diagnose these unusual fractures reliably. CT
      delineates the configuration of the fracture. In young patients open reduction
      and internal fixation seems preferable to replacement of the humeral head, since
      we have shown that the head is potentially viable.

PMID- 11341433
TI  - Characteristics of degeneration in an unstable knee with a coronal surface step
      off.
AB  - To investigate the effect of instability on the remodelling of a minor articular
      surface offset, we created a 0.5 mm coronal step-off of the medial femoral
      condyle in 12 New Zealand white rabbits and transected the anterior cruciate
      ligament (ACL). A control group of 12 rabbits had only ACL resection and the
      opposite knee was used as the non-operated control. The osteoarthritic changes at
      6, 12 and 24 weeks after surgery were evaluated histologically. In addition,
      changes in the immunological detection of 3-B-3(-) and 7-D-4 chondroitin-6
      sulphate epitopes were determined because of the previous association of such
      changes with repair of cartilage and early osteoarthritis. In the
      instability/step-off group there was rapidly progressing focal degeneration of
      cartilage on the high side of the defect, not seen in previous step-off studies
      in stable knees. The rest of the femoral condyles and the tibial plateaux of the
      instability/step-off group had moderate osteoarthritis similar to that of the
      instability group. 3-B-3(-) was detectable in the early and the intermediate
      stages of osteoarthritis but no staining was seen in the severely damaged
      cartilage zones. Immunoreactivity with 7-D-4 increased as degeneration
      progressed.

PMID- 11341434
TI  - Implant fixation enhanced by intermittent treatment with parathyroid hormone.
AB  - The intermittent administration of parathyroid hormone (PTH) increases the
      formation of bone by stimulating osteoblastic activity. Our study evaluates the
      possibility that intermittent treatment with PTH (1-34) may also enhance the
      implant-bone fixation of stainless-steel screws. Twenty-eight rats received one
      screw in either one (n = 8) or in both (n = 20) proximal tibiae. We administered
      either PTH (1-34) in a dosage of 60 microg/kg/day (n = 14) or vehicle (n = 14)
      over a period of four weeks. At the end of this time, the degree of fixation was
      assessed by measuring the removal torque on one screw in each rat (n = 28) and
      the pull-out strength on the contralateral screw (n = 20). PTH increased the mean
      removal torque from 1.1 to 3.5 Ncm (p = 0.001) and the mean pull-out strength
      from 66 to 145 N (p = 0.002). No significant differences in body-weight or ash
      weight of the femora were seen. Histological examination showed that both groups
      had areas of soft tissue at the implant-bone interface, but these appeared less
      in the PTH group. These results indicate that intermittent treatment with PTH may
      enhance the early fixation of orthopaedic implants.

PMID- 11341435
TI  - Sealing effect of hydroxyapatite coating on peri-implant migration of particles.
      An experimental study in dogs.
AB  - We have studied the beneficial effects of a hydroxyapatite (HA) coating on the
      prevention of the migration of wear debris along the implant-bone interface. We
      implanted a loaded HA-coated implant and a non-coated grit-blasted titanium alloy
      (Ti) implant in each distal femoral condyle of eight Labrador dogs. The test
      implant was surrounded by a gap communicating with the joint space and allowing
      access of joint fluid to the implant-bone interface. We injected polyethylene
      (PE) particles into the right knee three weeks after surgery and repeated this
      weekly for the following five weeks. The left knee received sham injections. The
      animals were killed eight weeks after surgery. Specimens from the implant-bone
      interface were examined under plain and polarised light. Only a few particles
      were found around HA-coated implants, but around Ti implants there was a large
      amount of particles. HA-coated implants had approximately 35% bone ingrowth,
      whereas Ti implants had virtually no bone ingrowth and were surrounded by a
      fibrous membrane. Our findings suggest that HA coating of implants is able to
      inhibit peri-implant migration of PE particles by creating a seal of tightly
      bonded bone on the surface of the implant.

PMID- 11341436
TI  - Effect of PMMA particles and movement on an implant interface in a canine model.
AB  - The pathogenesis of aseptic loosening of total joint prostheses is not clearly
      understood. Two features are associated with loosened prostheses, namely,
      particulate debris and movement of the implant. While numerous studies have
      evaluated the cellular response to particulate biomaterials, few have
      investigated the influence of movement of the implant on the biological response
      to particles. Our aim was therefore to test the hypothesis that excessive
      mechanical stimulation of the periprosthetic tissues induces an inflammatory
      response and that the addition of particulate biomaterials intensifies this. We
      allocated 66 adult Beagle dogs to four groups as follows: stable implants with
      (I) and without (II) particulate polymethylmethacrylate (PMMA) and moving
      implants with (III) and without (IV) particulate PMMA. They were then evaluated
      at 2, 4, 6, 12 and 24 weeks. The stable implants were well tolerated and a thin,
      fibrous membrane of connective tissue was observed. There was evidence of
      positive staining in some cells for interleukin-6 (IL-6). Addition of particulate
      PMMA around the stable implants resulted in an increase in the fibroblastic
      response and positive staining for IL-6 and tumour necrosis factor-alpha (TNF
      alpha). By contrast, movement of the implant resulted in an immediate
      inflammatory response characterised by large numbers of histiocytes and cytokine
      staining for IL-1beta, TNF-alpha and IL-6. Introduction of particulate PMMA
      aggravated this response. Animals with particulate PMMA and movement of the
      implant have an intense inflammatory response associated with accelerated bone
      loss. Our results indicate that the initiation of the inflammatory response to
      biomaterial particles was much slower than that to gross mechanical instability.
      Furthermore, when there was both particulate debris and movement, there was an
      amplification of the adverse tissue response as evidenced by the presence of
      osteolysis and increases in the presence of inflammatory cells and their
      associated cytokines.

PMID- 11341437
TI  - Anatomical reduction of intra-articular fractures of the distal radius.

PMID- 11341438
TI  - Meta-analysis of thromboembolic prophylaxis after total knee arthroplasty.

PMID- 11341439
TI  - Proximal femoral bone loss and increased rate of fracture with a proximally
      hydroxyapatite-coated femoral component.

PMID- 11341440
TI  - The orthopaedic management of peripheral ischaemia in meningococcal septicaemia
      in children.

PMID- 11341441
TI  - Interstitial laser photocoagulation for the treatment of osteoid osteoma.

PMID- 11341442
TI  - Clinical outcome of congenital talipes equinovarus diagnosed antenatally by
      ultrasound.

PMID- 11341443
TI  - Clinicopathological report Periocular tumour of the follicular infundibulum.
AB  - Tumour of the follicular infundibulum (TFI) is an uncommon, benign lesion of the
      skin adnexae. Four cases are reported of periocular TFI. In all cases a clinical
      diagnosis of basal cell carcinoma was made before surgery; however, histopatholog
      ca examination revealed TFI. This is an epithelial tumour showing differentiation
      along the lines of the follicular infundibulum. Characteristic features are a
      shelf-like proliferat on of pale epithelia cells in the upper dermis, attachment
      to the epidermis and the upper portions of the pilosebaceous units, a dense
      border of elastic fibres, and palisading of the peripheral cell layer of the
      tumour plate. This benign tumour has not, to the authors' knowledge, been
      reported in the ophthalmic literature. It has a non-specific appearance and may
      be clinically misdiagnosed as naevus sebaceous, xanthoma, seborrhoeic keratosis,
      or basal cell carcinoma.

PMID- 11341444
TI  - Detection and treatment of diabetic retinopathy.

PMID- 11341445
TI  - Uveitis: what do we know and how does it help?
AB  - Uveitis essentially means intraocular inflammation and encompasses a wide variety
      of different disorders. This includes both mild and severe types of inflammation
      affecting different parts of the eye. Histologically, all uveitis is
      characterized by an influx of lymphocytes into the affected tissue. In all types
      these lymphocytes are predominantly of the CD4 type, whether the disorder is mild
      or blinding, giving no clue as to why. New studies comparing cells in ocular
      fluids taken from inflamed eyes with different types of inflammation have, for
      the first time, shown a difference in the cytokine profile, so that in visually
      benign disease interleukin 10 levels are higher than in those which are
      blinding.The potential for this in terms of therapy is discussed.

PMID- 11341446
TI  - Diabetic retinopathy: effects of national guidelines on the referral, examination
      and treatment practices of ophthalmologists and optometrists.
AB  - OBJECTIVE: To investigate the changes in referral, examination and treatment
      practices for diabetic retinopathy by ophthalmologists and optometrists following
      the release of national guidelines. METHODS: A two-page self-administered
      questionnaire was mailed to all Australian ophthalmologists and a random sample
      of 500 Australian optometrists prior to and 1 year after release of the National
      Health and Medical Research Council of Australia (NHMRC) clinical practice
      guidelines for the management of diabetic retinopathy. The questionnaires
      elicited information about current practice related to the management of patients
      with diabetic retinopathy. RESULTS: Of the 464 contactable ophthalmologists who
      responded to the baseline survey, 374 (80.6% response) completed the follow-up
      survey The response rate for the contactable optometrists was 80.1% (310 of 384).
      There were almost no significant changes in management practices from baseline to
      follow up. For example, the percentage of ophthalmologists who reported that they
      were often or almost always confident in detecting moderate retinal thickening
      near the macula remained nearly identical from baseline to follow up (80.2% vs
      79.1 %). The rate was also similar from baseline to follow up for optometrists
      (31.1% vs 28.8%). The one area in which ophthalmologists reported significant
      changes in management towards agreement with the NHMRC guidelines was use of
      angiography; they were less likely to manage their patients this way (20.4% vs
      14.2% with laser and 48.9% vs 38.4% without laser for increasing level of
      severity in clinical signs; both P < 0.05). CONCLUSIONS: The NHMRC guidelines for
      diabetic retinopathy have been successfully distributed to ophthalmologists and
      optometrists in Australia. However, the mere provision of the guidelines has had
      little impact on management practices. It will be important to determine if
      ongoing dissemination and implementation strategies not only increase awareness
      of health-care practitioners to the guidelines, but also change behaviours.

PMID- 11341447
TI  - Ophthalmologists in teaching hospitals: do we make a difference to patient
      outcome?
AB  - PURPOSE: To determine the type and frequency of consultations with the eye
      department of a major tertiary care teaching hospital. METHODS: A retrospective
      review was undertaken of the medical records of npatient consultations within the
      Ophthalmology Department of Royal Prince Alfred Hospital over the period from
      July 1995 to 30 June 1997. The consults were dvided into sx types of
      consultation. A determination was made of the outcome and effect on patient
      management of each consultation. RESULTS: There were 506 consultations over the 2
      year period. For 389 patients a full ophthalmic assessment was requested and 175
      of them (45%) had an ophthalmological diagnosis made or had change in management
      as a result of the consultation. CONCLUSION: Ophthalmological consultation is a
      valuable npatient consultation service that makes a significant difference in the
      management of patients from other medical and surgical units within the hospital.

PMID- 11341448
TI  - Evaluation of the quality of generic polymethylmethacrylate intraocular lenses
      marketed in India.
AB  - PURPOSE: To determine the quality of single-piece, allpolymethylmethacrylate
      (PMMA) Intraocular lenses (IOLs) from eght generic manufacturers marketing their
      product in India. This assessment of quality was made with respect to compliance
      with internationa standards for the manufacture of IOLs, specifically those
      parameters most likely to affect patient postoperat ve visual acuity and the long
      term biocompatibility of the implanted lens. METHODS: Ten IOLs from each of eight
      manufacturers were purchased randomly from commercial retail outlets in India.
      Each IOL, in a masked fashion, had its physical dimensions, optical performance
      and cosmetic appearance assessed, using the methods prescribed in ISO 11979-2 and
      11979-3. Validation of manufacturing process controls were determined by
      statistical process contro techniques. Four IOLs from each manufacturer were also
      tested for the presence of unpolymerized PMMA using gas chromatography. RESULTS:
      Only lenses from two IOL manufacturers complied with the optical and mechanical
      standards. All other manufacturers' lenses failed one or more of these tests.
      Intraocular lenses from only two producers met with surface quality and bulk
      homogeneity standards. All others exhibited defects such as surface contamination
      and scratches, poor polishing, and chipped or rough positioning holes. Lenses
      from two producers exhibited high levels of methylmethacrylate monomer (MMA).
      CONCLUSIONS: Non-clinical grade PMMA starting material may have been used in the
      manufacture of IOLs by some producers. Critical manufacturing defects occurred in
      the IOLs from five of the eight producers tested. Only one manufacturer's IOLs
      met all specifications, and on statistical analysis demonstrated good
      manufacturing process contro with respect to the properties tested. With the
      widespread acceptance of IOL implantation in developing countries, such as India,
      it is essential that in the rush to make this the norm, the quality of implants
      used not be overlooked.

PMID- 11341449
TI  - Visual outcomes for remote Australian Aboriginal people after cataract surgery.
AB  - PURPOSE: To assess the visual outcomes and quality of life after cataract surgery
      in Aborig nal people and compare them with a case-matched population of non
      Aborginal people living in remote and rural areas in the Top End of the Northern
      Territory. METHODS: Patients living in remote areas of the Top End of the
      Northern Territory who underwent cataract surgery between 1994 and 1999 were
      identified from records at the three major hospitals in the region. Eighty-three
      patients were included in the study. Each patient underwent a complete ocular
      assessment and then was administered a standardized, field-tested, 12-item
      questionnaire concerning visual function. This was analyzed and the results of
      the Aboriginal and matched non-Aboriginal populations compared. RESULTS: Sixty
      one Aboriginal and 22 non-Aboriginal people from a total of 295 patients who
      underwent cataract surgery were included in the study. The two study groups were
      closely matched by sex, age at the time of surgery, time of follow up from
      surgery and the number who had undergone bilateral surgeryThe median preoperative
      visual acuity for the Aboriginal group was 6/60 against 6/24 of the non
      Aboriginal group. After surgery, at the time of follow up, 26% of eyes in
      Aboriginal patients did not correct to 6/12 or better with pinhole approximation.
      Posterior capsule opacities were the most common principal postoperative cause
      for a deterioration of visual acuity in both groups. Postoperatve trauma was a
      common cause for a low best-corrected visual acuity n the Aboriginal group but
      not in the non-Aboriginal group. The majority (75.5%) of Aboriginal patients were
      satisfied with their operated eyes. Patients who were dissatisfied all had a
      visual acuity worse than 6/36. Aborigina patients reported worse visual function
      than did those in the non-Aboriginal group. CONCLUSIONS: Cataract surgery has a
      beneficial effect on the visual acuity and quality of life of Aboriginal and non
      Aboriginal people. As compared to their non-Aboriginal counterparts, most
      Aboriginal people underwent surgery when they were legally blind, had a lower
      level of attained postoperative visual acuity and a high incidence of uncorrected
      refractive errors and posterior capsular opacification requiring laser
      capsulotomy. The positive mpact of cataract surgery on the lives of the majority
      of Aboriginal patients is highlighted, as is the need for continued postoperative
      follow up.

PMID- 11341450
TI  - Childhood cataracts.
AB  - OBJECTIVE: The aim of this study was to determine the surgical outcome of
      childhood cataracts. METHOD: Between 1990 and 1997, 137 patients less than 10
      years of age (181 eyes) underwent cataract surgery at the Royal Alexandra
      Hospital for Children/New Children's Hospital. Data were collected
      retrospectively from medical records and supplemented with data from referrng
      ophthalmologists. RESULTS: In the majority of patients (53.0%), the cause of
      cataract was unknown. Sixty-two patients (45.3%) had bilateral and 75 patents
      (54.7%) had unilateral cataracts. In 84 patients (107 eyes: 59.1%), the onset of
      visually significant cataract was estimated to be before the age of 2 years.
      Reliable postoperatve visual acuity (VA) was obtained in 150 eyes from 116
      patients. The mean LogMAR VA was 0.71 +/- 0.55 in bilateral cataracts and 1.17 +/
      0.68 in unilateral cataracts. Visual acuity was poor (LogMARVA > 1.0) in 71.8%
      of unilateral cataracts (compared to 27.9% in bilateral cataracts, P < 0.0001),
      and in 64.9% when onset was ess than 2 years (compared to 22.4% in later onset
      cataract, P < 0.0001). Posterior capsular opacity requiring laser or surgical
      removal was noted in 40 patients (44 eyes; 24.4%). Other complications included
      raised intraocular pressure in six patients (seven eyes: 3.7%), displaced
      intraocular lens or iris capture in 11 patients (12 eyes; 6.6%), ectopic pupil in
      five patients (five eyes; 2.7%), and severe inflammation in eight patients (12
      eyes; 6.6%). There was cosmetically significant esotropia or exotropia in 24
      patients (23 eyes; 12.7%). CONCLUSION: The prognosis for vision was significantly
      poorer in unilateral and earlier onset cataract. The importance of early
      diagnosis, prompt treatment and vigilant postoperative follow up in this subgroup
      cannot be overemphasized.

PMID- 11341451
TI  - Pars planitis: a comparison of childhood onset and adult onset disease.
AB  - PURPOSE: To compare the symptoms, visual acuities and complications found in
      childhood onset pars planitis, with those seen in adult onset disease. METHOD:
      The records of 26 patients (52 eyes) with idiopathic pars planitis seen at a
      tertiary care clinic were reviewed. The study design allowed comparison of follow
      up visual acuities for the adult onset and childhood onset groups at 2 years and
      5 years from the time of initial diagnosis. RESULTS: The visual acuity at the
      time of initial diagnosis, at 2 years' follow up and at 5 years' follow up was
      worse for children than for adults, but this difference only reached statistical
      significance at 2 years' follow up (6/10 vs 6/7; P = 0.026). When looking at
      correlation coefficients between age and acuity, the same trend was observed at
      all time intervals, only reaching statistical significance with initial visual
      acuities (r = 0.32; P = 0.019). Adults had a tendency to complain more at
      presentation of blurred vision and floaters than children. Complication rates
      were similar for both groups. CONCLUSION: The study presents data supporting the
      idea that patients presenting with idiopathic pars planitis in childhood have a
      worse visual acuity both at initial diagnosis and at follow up than those
      presenting in adulthood. This is a long-suspected finding that has not previously
      been demonstrated.

PMID- 11341452
TI  - Transcaruncular medial orbitotomy for stabilization of the posterior limb of the
      medial canthal tendon.
AB  - PURPOSE: A method to stabilize the posterior limb of the medial canthal tendon
      (MCT), using a transcaruncular medial orbitotomy (TMO) approach, is described in
      a stepwise fashion. The technique described is a modified version of procedures
      published by Ritleng, Crawford and Collin, and Fante and Elner METHODS: A
      prospective clinical evaluation of MCT stabilization via the TMO approach was
      undertaken in I I consecutive patients who presented with MCT laxity as one of
      the features of their ectropion. These cases are initially described in detail in
      two representative case reports, and summarized in 11 cases. The stepwise
      surgical approach is outlined. RESULTS: All patients had improved symptomatology
      in terms of epiphora and comfort. Furthermore, in all cases the lid position was
      improved or normalized. In four of the I cases (36%) the lower punctum did not
      ultimately reside in the lacrimal ake, but the punctal position was nevertheless
      improved and the MCT was stabilized. CONCLUSION: The TMO procedure provides both
      excellent MCT stabilization and adequate placement of the lower lacrimal punctum
      onto the globe. It does not require canalicular resection, and avoids continued
      anterior displacement of the medial lower lid which may occur when only the
      anterior limb of the MCT is addressed surgically.

PMID- 11341453
TI  - Prepapillary vascular loops.
AB  - A case is reported of a 10-year-old girl with prepapillary vascular loops. These
      are normal blood vessels of excessive length, usually arterial, that project from
      the optic disc into the vitreous cavity. Stereoscopic photographs and fluorescein
      angiographs of the condition are presented.

PMID- 11341454
TI  - Bacillus circulans endophthalmitis.
AB  - An 80-year-old woman presented with right endophthalmitis, characterized by
      chalky white deposits covering her posterior capsule. This occurred 17 months
      after uncomplicated right cataract surgery. A three-port pars plana vitrectomy
      and partial posterior capsulectomy isolated Bacillus circulans, and the patient
      made a rapid and full recovery on topical cephalothin and prednisolone acetate
      1%. The case demonstrates that, unlike endophthalmitis due to other Bacillus
      spp., B. circulans endophthalmitis does not necessarily follow a fulminant
      course. It is the first report describing a subacute presentation, and response
      to posterior capsulectomy and simple antibiotic therapy It is also the first
      description of B. circulans causing white plaques in the posterior capsule, a
      finding characteristic of chronic endophthalmitis and previously considered
      pathognomonic of Proprionibacterium acnes endophthalmitis.

PMID- 11341455
TI  - Simultaneous choroidal melanoma and rhegmatogenous retinal detachment.
AB  - A case is reported of a 30-year-old man who presented with the unusual
      combination of a unilateral inferonasal choroidal melanoma and an unassociated
      rhegmatogenous retinal detachment attributable to a large horseshoe tear in the
      superotemporal quadrant. Over 20 cases of simultaneous occurrence of these two
      phenomena have now been reported but this patient appears to be the youngest. The
      reports of this uncommon association are reviewed.

PMID- 11341456
TI  - Orbital inflammation in a patient with extrascleral spread of choroidal malignant
      melanoma.
AB  - An elderly woman presented with fever, dehydration, orbital inflammation, total
      external and internal ophthalmoplegia and blindness, resembling the clinical
      appearance at presentation of severe orbital inflammatory disease or
      mucormycosis. Orbital computed tomography scanning demonstrated a retrobulbar
      orbital mass. Subsequent B-scan ultrasound examination confirmed the orbital mass
      but also demonstrated a mass within the eye. At lateral orbitotomy, extrascleral
      spread of an entirely necrotic intraocular melanoma was demonstrated. As computed
      tomography scanning may not be able to delineate an entirely necrotic intraocular
      malignant melanoma, B-scan ultrasonography should be considered in patients with
      orbital inflammation, especially in the presence of a retrobulbar mass.

PMID- 11341457
TI  - 20 years ago: the British Homoeopathic Journal, April 1981.

PMID- 11341458
TI  - Long-term follow-up after homeopathic treatment of chronic headache. Do not
      generalise from such a special case.

PMID- 11341459
TI  - The long-term effects of homeopathic treatment of chronic headaches: one year
      follow-up and single case time series analysis.
AB  - Little is known about long-term effects of homeopathic treatment. Following a
      double-blind, placebo controlled trial of classical homeopathy in chronic
      headaches, we conducted a 1-year observational study of 18 patients following the
      double-blind phase, and a complete follow-up study of all trial participants.
      Eighteen patients received free treatment for daily diary data (frequency,
      intensity, duration of headaches) over the course of 1 y. All patients enrolled
      in the double-blind study were sent a 6-week headache diary, a follow-up
      questionnaire, a personality inventory and a complaint list. Eighty-seven, of the
      original 98 patients enrolled returned questionnaires, 81 returned diaries. There
      was no additional change from the end of the trial to the one-year follow-up. The
      improvement seen at the end of the 12-week trial was stable after 1 y. No
      differential effects according to treatment after the trial could be seen.
      Patients with no treatment following the trial had the most improvement after 1
      y. Five of 18 patients can be counted responders according to ARIMA analysis of
      single-case time-series. Patients with double diagnoses and longer treatment
      duration tended to have clearer improvements than the rest of the patients.
      Approximately 30% of patients in homeopathic treatment will benefit after 1 y of
      treatment. There is no indication of a specific, or of a delayed effect of
      homeopathy.

PMID- 11341460
TI  - Prophylactic and acute treatment with the homeopathic medicine, Betula 30c for
      birch pollen allergy: a double-blind, randomized, placebo-controlled study of
      consistency of VAS responses.
AB  - A study of the consistency of responses by allergic patients in repeated studies
      of the homeopathic remedy Betula 30c or placebo against birch pollen allergy, was
      made. A randomized, double-blind, placebo-controlled trial was performed
      including participants with a known allergy to birch pollen. Allergy symptoms
      were assessed on a visual analogue scale (VAS) by patients or parents each day
      during a 20-day period during two different pollen seasons. The work was carried
      out in Oslo, Norway during May 1995, 1996 and 1997. There were 51 patients
      ranging in age from 7 to 50y. The homeopathic remedy Betula 30c or placebo was
      given as tablets, both as a prophylactic agent, once a week for 4 weeks before
      the pollen season started, and as an acute remedy during the pollen season. The
      mean value of the symptom scores on the visual analogue scale, for all
      registration days from each patient was the main outcome. The patient groups that
      received either placebo or Betula 30c for two successive years showed a
      consistent response (r=0.75, P=0.01 and r=0.70, P=0.003, respectively). No such
      correlation was found in the two groups that changed remedy from one year to
      another (either from placebo to Betula or vice versa). Subjective assessment of
      allergic symptoms to birch pollen differed more from one year to another when
      different regimens (placebo or homeopathic) had been administered these two
      seasons, than when the same treatment had been given.

PMID- 11341462
TI  - Homeopathic Secretin in autism: a clinical pilot study.
AB  - Autism is a condition characterised by impairments of social communication,
      social interaction and social imagination. The exact aetiology of autism is
      unknown but some autistic features have been explained by the 'opioid excess
      theory' in which excess brain peptide levels have a morphine-like activity.
      Reduction of peptide levels by administration of the duodenal enzyme Secretin has
      been found to improve social and language skills in autistic patients.
      Homeopathic Secretin has been said to produce similar effects. A pilot study was
      undertaken to study these effects by administration of Secretin to a group of
      autistic patients. Weekly assessment for 12 weeks was performed by the patients'
      care workers. Statistical analysis of the mean pre-treatment results compared
      with the mean treatment results suggested a worsening in the autistic symptoms
      during treatment. Discussion with the care workers revealed changes and some
      improvements that were not recordable on the scoring system. Further research
      into Secretin treatment of autism using a more detailed and customized scoring
      system would be justified. Following this pilot study a randomised controlled
      trial of Secretin vs placebo would be appropriate.

PMID- 11341461
TI  - Nux vomica 30 prepared with and without succession shows antialcoholic effect on
      toads and distinctive molecular association.
AB  - Adult toads, Bufo melanostictus, were administered Nux vomica (Nux v) 30 prepared
      with and without succussion on the tongue. The drug was mixed with sterile
      distilled water at the rate 0.05ml/ml water and given orally 0.05ml/individual.
      The control consisted of blank ethanol solution. Seeds of Strychnos nuxvomica
      were ground and extracted with 90% ethanol in the laboratory. Nux v 30 was
      prepared by successive dilution and succussion in 30 steps, Nux v 30 u was
      prepared by successive dilution only. Four hours after treatment, toads were
      given 25% ethanol i.p. at 8g/kg body weight. The duration of ethanol induced
      sleep time was recorded for each toad. Both Nux v 30 and Nux v 30 u significantly
      reduced ethanol induced sleep time in toads as compared to their respective
      controls. Electronic, infra red and nuclear magnetic resonance spectra of Nux v
      30, Nux v 30 u and their diluent medium (90% ethanol) show marked differences
      from each other. These dilutions and ethanol 30 and ethanol 30 u show marked
      differences from each other with respect to spin-lattice relaxation time (T1) and
      chemical shift. The difference has been attributed to the variation in intra and
      inter-molecular association of ethanol and water.

PMID- 11341463
TI  - On the scientific status of homeopathy.
AB  - Critics of homeopathy often claim that it is non-scientific. By offering adequate
      tools for the analysis of the foundations, structure and implications of
      scientific theories, philosophy of science can help to clarify this medical
      controversy. However, homeopathy has not yet attracted the attention of
      philosophers of science to any noticeable extent. Among the many topics to which
      philosophy of science could contribute, this paper selects two, not only for
      their intrinsic importance, but also because they are essential for any fruitful
      discussion of the rest. It is shown, first, that in homeopathy, as developed by
      Hahnemann, two related, but distinct theoretical levels can be identified. Then
      it is indicated that at least one of them-the phenomenological level-can be seen
      as embodying a largely autonomous research programme, on which homeopathic
      medical practice can rest. Finally, it is argued that this programme displays the
      basic theoretical and methodological traits of a genuine science, according to an
      influential contemporary approach in philosophy of science. Some
      misunderstandings involved in the debate are pointed out.

PMID- 11341464
TI  - Homeopathy in the USA.
AB  - Homeopathy was introduced into the USA by Hans Burch Gram in 1825. It developed
      largely through immigration of German homeopaths. The first homeopathic medical
      college was established in Allentown, PA in 1835. The American institute of
      Homeopathy (AIH) was founded in 1844. The American Medical Association was
      founded in 1847 and pursued policies hostile to homeopathy from the outset.
      Eclectic medicine was widespread in nineteenth century medicine, one of the
      greatest homeopaths, JT Kent had originally been an eclectic. The International
      Hahnemannian Association split from the AIH in 1880. The Flexner Report of 1910
      resulted in many homeopathic medical colleges being closed down. Homeopathy in
      the USA was in steep decline from the 1920s to the 1960s but has had a strong
      recovery since the 1970s.

PMID- 11341465
TI  - Induction of hepatic metallothioneins in tumor-bearing IL-6-null mice.
AB  - Interleukin-6 (IL-6) has been thought to play a key role in the induction of
      hepatic metallothionein (MT) synthesis in tumor-bearing animals. In order to
      clarify the role of IL-6 and to distinguish its effect from those of other
      cytokines, we inoculated IL-6-null and B6J129Sv (wild-type control) mice SC with
      1 x 10(7) Ehrlich carcinoma cells and examined tumor growth, hepatic MT, and
      serum cytokines. We have found that tumor growth was followed by an increase of
      hepatic MT in both IL-6-null and wild-type mice and that the two strains of mice
      had a similar hepatic MT induction followed by zinc accumulation in the liver.
      These results could be explained by our finding that tumor-bearing IL-6-null mice
      had a high level of tumor-secreted IL-6 in the blood. In conclusion, by utilizing
      tumor-bearing IL-6-null mice, we have demonstrated that IL-6 secreted from the
      tumor cells is responsible for the tumor-evoked increase of hepatic MT level.

PMID- 11341466
TI  - Human interferon-gamma enhances expression of ganglioside GM2 on human lung
      cancer cells and their susceptibility for antiganglioside GM2 monoclonal antibody
      dependent cellular cytotoxicity.
AB  - Interferons are known to modulate several cellular functions by the induction of
      various proteins. In this study, we demonstrated that human interferon-gamma
      (HuIFN-gamma) enhanced the expression of ganglioside GM2 (GM2), which is a kind
      of tumor-associated antigen substantially expressed in human lung cancer and that
      human lung cancer cells expressing GM2 became more susceptible to anti-GM2
      monoclonal antibody (mAb)-dependent tumor cell killing mediated by human effector
      cells after HuIFN-gamma treatment. GM2 expression on human lung cancer cells
      treated with or without HuIFN-gamma was measured by flow cytometry. The antibody
      dependent cellular cytotoxicity (ADCC) activity was assessed by 4-h 51Cr release
      assay. HuIFN-gamma enhanced GM2 expression on human small-cell lung cancer
      (SCLC), SBC-3, and human non-small-cell lung cancer (NSCLC), A549 cells in a dose
      dependent manner. The optimal concentration of HulIFN-gamma was 1,000 U/ml. The
      effect of HulFN-gamma reached maximum after 4 days of culture. HulFN-gamma did
      not have any effect to enhance the expression of other gangliosides in SBC-3
      cells. No other cytokines used in this study modulated GM2 expression in SBC-3
      cells. Anti-GM2 mAb-dependent ADCC activities induced by lymphocytes and
      monocytes were more potent against IFN-gamma-treated SBC-3 and A549 cells than
      nontreated cells. Taken together, HulFN-gamma combined with anti-GM2 mAb may be
      useful for immunotherapy against GM2-positive human lung cancer.

PMID- 11341467
TI  - Expression of the ATF3 gene on cell lines and surgically excised specimens.
AB  - TI-241 (ATF3 homologue gene) is a metastasis-associated gene that is expressed at
      higher levels in the high-metastatic mouse B16 melanoma subline B16-FIO than in
      the low-metastatic clone Fl. We studied ATF3 expression in established cell lines
      of human colon and stomach cancer and surgically excised human colon cancer. ATF3
      was expressed at higher levels in the cell lines that were established from
      metastatic sites than in those from original tumor sites. Also ATF3 was expressed
      at higher levels in tumor specimens than in adjacent normal mucosa. especially in
      the tumors that had invaded the lymphatic ducts and/or the vessels, while there
      was not a significant relationship hetween its expression and the other
      pathological features. As metastasis is the most important factor in determining
      prognosis, these results show the potential for ATF3 in making the prognosis.

PMID- 11341468
TI  - 4-[3-(2-Nitro-1-imidazolyl)propylamino]-7-chloroquinoline hydrochloride (NLCQ-1),
      a novel bioreductive compound as a hypoxia-selective cytotoxin.
AB  - A novel weakly DNA-intercalative bioreductive compound. 4-[3-(2-nitro-1
      imidazolyl)-propylamino]-7-chloroquinoline hydrochloride (NLCQ-1). has been
      synthesized and studied as a hypoxia-selective cytotoxin in vitro. NLCQ-1, which
      shares a similar structure with the DNA-intercalative antimalarial drug
      chloroquine, bound more strongly to DNA than the nonchlorinated analog NLQ-1 (4
      [3-(2-nitro-1-imidazolyl)propylamino]-quinaldine hydrochloride). Thus, NLCQ-1
      exhibited a C50 [concentration for 50% displacement of the ethidium bromide (EB)
      from a DNA-EB complex] of 44 microM, whereas a C50 value could not be reached for
      NLQ-1 up to 225 microM. NLCQ-1 demonstrated significant hypoxic selectivity in
      several rodent (V79, EMT6, SCCVII) or human (A549, OVCAR-3) tumor cell lines. Its
      potency as a hypoxic cytotoxin (expressed as the product of exposure time and
      concentration for 50% survival) ranged between 10 and 136 microM x h, for the
      cell lines tested, at 30 microM input concentration. Because uptake in all cell
      lines was similar, the differences in potency may reflect differences in the
      enzymatic profile or damage repair processes among the cell lines. In addition,
      however, the most striking feature of NLCQ-1 was that hypoxic selectivity
      increased with exposure time, a common feature normally found in only bis
      bioreductive agents carrying two moieties with different redox potentials. Thus,
      hypoxic selectivity of NLCQ-1 in V79 cells at 50% survival was increased from
      fivefold up to 388-fold by increasing exposure time from 1 to 4.5 h, as the
      result of a concomitant increase and decrease in its hypoxic and aerobic potency,
      respectively, over time. Because the nonchlorinated analog NLQ-1 did not
      demonstrate similar behavior, we hypothesized that the C-7 chlorine of NLCQ-1
      might play a significant role in this phenomenon.

PMID- 11341469
TI  - Sodium butyrate-induced differentiation of human LIM2537 colon cancer cells
      decreases GSK-3beta activity and increases levels of both membrane-bound and
      Apc/axin/GSK-3beta complex-associated pools of beta-catenin.
AB  - Analysis of the glycogen synthase kinase-3beta (GSK-33) activity in several colon
      cancer cell lines suggested a correlation between comparatively low enzyme
      activity and moderate to high differentiation status. Treatment of LIM2537 cells,
      a poorly differentiated colon cancer cell line, with the potent differentiating
      agent sodium butyrate resulted in 34% reduction in GSK-3beta activity in the
      treated cells (P < 0.028, n = 3). Decreases in GSK-3beta activity were paralleled
      by stabilization of cytoplasmic beta-catenin, a hallmark of Wnt signaling.
      However, in contrast to Wnt signaling, expression of the beta-catenin/ TCF target
      genes c-myc and cyclin D1 did not appear to be increased in the sodium butyrate
      treated cells. Interestingly, expression of membrane-bound beta-catenin was
      increased in the sodium butyrate-treated cells. This suggests that, in the
      context of cellular differentiation, increases in beta-catenin expression may be
      sequestered at the cell membrane and suggests that a possible role of sodium
      butyrate in promoting differentiation may be via increasing the levels of beta
      catenin available for cell adhesion.

PMID- 11341470
TI  - Angiogenesis and p53 expression in the colorectal adenoma-carcinoma sequence.
AB  - Angiogenesis, the formation of new vessels, is essential for tumor growth and
      metastasis. Mutations of p53 tumor suppressor gene are frequent and play an
      important role in colorectal oncogenesis. A role of p53 as an angiogenesis
      inhibitor has also been proposed. We evaluated angiogenesis and p53 expression in
      16 hyperplastic polyps, 35 solitary tubular and tubulovillous adenomas, and 47
      cases of sporadic colorectal carcinomas arising on the basis of preexisting
      adenomas, with standard immunohistochemical techniques. The mean microvessel
      density (MVD) in carcinomas was significantly higher compared with the respective
      adenomatous part of the same tumor (27.9 vs. 7; P=0.0001). Linear regression
      analysis of MVD between cancerous and adenomatous areas showed a significant
      correlation (P = 0.0001, r = 0.56), raising the possibility that carcinomas
      arising from better vascularized adenomas might show increased vascularity. The
      MVD was significantly higher in stage C compared with stage A cases (P=0.04). p53
      positivity was detected in 26 of 47 cancerous (55%) and in 14 of 47 adenomatous
      areas (30%; P = 0.0002). All carcinomas arising from p53-positive adenomas were
      also p53 positive. p53 positivity associated with a higher MVD in adenomas (P =
      0.02), but not in carcinomas (P = 0.78). We conclude that angiogenesis and p53
      play a critical role in colorectal neoplasia, and the process of malignant
      transformation in tumors arising from highly angiogenic adenomas, particularly
      those carrying p53 mutations, is accelerated with rapid tumor progression from
      stage to stage, indicating a more aggressive tumor phenotype.

PMID- 11341472
TI  - A practical guide to antimicrobial management of complicated urinary tract
      infection.
AB  - Complicated urinary tract infection occurs in the setting of a functionally or
      structurally abnormal genitourinary tract. Many different abnormalities may lead
      to a designation of complicated urinary tract infection, and these abnormalities
      will have different influences on the frequency of infection and likelihood of
      relapse or reinfection. The microbiology of complicated urinary tract infection
      is characterised by a greater variety of organisms and increased likelihood of
      antimicrobial resistance compared with acute uncomplicated urinary tract
      infection. Appropriate management requires a urine specimen for culture prior to
      institution of antimicrobial therapy, and ensuring that the underlying
      abnormality is fully characterised to determine whether it can be corrected. A
      wide variety of antimicrobial agents are effective for treatment, and are usually
      given for 7 to 14 days. If the underlying abnormality can be corrected,
      subsequent infections may be prevented. However, if the underlying abnormality
      cannot be corrected a high recurrence rate of infection, approaching 50% by 4 to
      6 weeks, is expected. Further study of complicated urinary tract infection is
      necessary, including determination of when asymptomatic bacteriuria warrants
      treatment, and exploration of nonantimicrobial approaches to management.

PMID- 11341471
TI  - Age-related macular degeneration: cost-of-illness issues.
AB  - Macular degeneration refers to the breakdown of cells in the centre of the
      retina. Some degeneration is an inevitable consequence of the aging process;
      however, when this is associated with loss of sight in the central part of the
      field of vision an underlying pathology is considered present. Among those aged
      55 years, the prevalence of the disease in the US was estimated at 1% rising to
      approximately 15% among those aged 80 years. Other studies estimate the
      prevalence of the disease to be higher and to be increasing. The main effect of
      the disease is to reduce the ability of the individual to engage in everyday
      activities that require clear central vision. It may also be associated with
      elevated risks of depression and increased levels of dependency. Currently there
      is no effective treatment for the majority of patients. For a minority (< 10%)
      laser photocoagulation therapy may be effective in reducing the risk of severe
      vision loss. Another treatment, photodynamic therapy, is in development and many
      others are at an experimental stage. This review sought to establish current
      knowledge on the cost of illness associated with age-related macular degeneration
      (ARMD). A search of the literature, together with direct communication with
      researchers in related fields and patient support/advocacy groups, was undertaken
      to ascertain current knowledge on the cost of illness of ARMD. While literature
      on the disease is extensive and literature on treatments is emerging, no
      substantive information on direct or indirect costs was found although evidence
      that loss of earnings may occur is beginning to emerge. Some information does
      exist on cost of illness in diabetic retinopathy, a disease with similarities to
      ARMD, though even for this disease gaps in knowledge are apparent and wide
      variations exhibited. Given current knowledge, it is not possible to report on
      the cost of illness for ARMD with confidence. The lack of information on the cost
      of illness in ARMD presents difficulties for researchers and policy makers in
      assessing the cost effectiveness of the existing treatment, as well as new
      treatments as they become available. Given developments in treatments and the
      increasing prevalence of the disease, it is important that cost-of-illness
      information is gathered for ARMD.

PMID- 11341473
TI  - Botulinum toxin A treatment of adult upper and lower limb spasticity.
AB  - This article discusses the treatment of spasticity with botulinum toxin A as a
      new approach in the neurological rehabilitation of patients after stroke.
      Clinical studies have been reviewed to provide information about target groups,
      technical aspects and the advantages and disadvantages of treating spasticity
      with botulinum toxin A. Open and controlled studies showed that the intramuscular
      injection of Dysport 500 to 1,500U or Botox 100 to 300U could reversibly relieve
      upper limb flexor and lower limb extensor spasticity. A reduced muscle tone, pain
      relief, better hand hygiene and improved walking function were the main benefits.
      Patients tolerated the treatment well. Activity or, if not possible, electrical
      stimulation of the injected muscles may enhance the effectiveness of the costly
      toxin. Serial casting is another option. With respect to the action of botulinum
      toxin A, it is suggested that the effect of the toxin could be mediated by
      paresis of both the extrafusal and intrafusal muscle fibres, thereby altering the
      afferent discharge in the muscle.

PMID- 11341474
TI  - Clinical implications of physiological changes in the aging heart.
AB  - Elderly individuals experience a disproportionate burden from cardiovascular
      disease. Global changes in aging will have a significant impact on the future of
      medical practice. However, most physicians have little formal training in
      geriatric medicine and sometimes fail to distinguish disease states from normal
      aging. Increasingly, it is recognised that a sedentary lifestyle may be
      responsible for a large fraction of the so-called 'age-related' changes in the
      cardiovascular system. Nonetheless, well characterised changes do occur in most
      individuals with aging. Loss of myocytes with subsequent hypertrophy of the
      remaining cells is usually observed. Calcification involving the conduction and
      valvular apparatus is seen in most elderly individuals and may predispose to the
      common arrhythmias of old age. Age-related loss of arterial compliance
      contributes to isolated systolic hypertension and left ventricular hypertrophy.
      Despite these changes, for the majority of healthy older adults, cardiac output
      is well maintained in the basal state through use of the Frank-Starling
      principle, in the setting of reduced early diastolic filling. Myocardial
      relaxation is slowed in part due to age-related changes in the sarcoplasmic
      reticulum Ca2+ ATPase pump. Elevated blood levels of catecholamines contribute to
      desensitisation to noradrenergic stimulation and this is associated with an age
      related decline in maximum achievable heart rate. Changes in the baroreceptor
      reflex function and decreased sodium conservation may predispose some individuals
      to orthostatic and postprandial hypotension. The aetiology of cardiovascular
      aging is under intense study. The most likely mechanisms involve the result of
      cumulative damage mediated through a variety of insults. Oxidative stress, non
      enzymatic glycation, inflammation and changes in cardiovascular gene expression
      all seem to influence cardiovascular aging. The benefits of exercise continue to
      be discovered. Endurance-type training has been shown to have a dramatic impact
      on parameters of cardiovascular aging. Favourable effects are seen in maximum
      oxygen consumption, diastolic filling, relaxation and arterial stiffness. Some
      changes such as the maximum heart rate response do not appear to change with
      conditioning. Pharmacotherapy may afford the opportunity to influence the aging
      process. Drugs that can reduce age-associated arterial stiffness, cardiac
      fibrosis and ventricular hypertrophy should prove useful. Antioxidants continue
      to be a topic of great interest and require more study. Despite some well
      described changes with aging, most elderly individuals maintain the opportunity
      for improved cardiovascular function through conditioning. Early recognition and
      treatment of diseases that are distinguishable from normal aging, including
      hypertension and atherosclerosis, together with preventive efforts, should reduce
      the predicted trends in cardiovascular morbidity and mortality among the aged.

PMID- 11341476
TI  - Characterization of 5-HT2A receptor desensitization and the effect of
      cycloheximide on it in C6 cells.
AB  - Effect of prolonged pretreatment with serotonin (5-HT) on 5-HT2A receptor
      desensitization was examined by the measurement of intracellular calcium
      ([Ca2+]i) mobilization in C6 cells. 5-HT-induced desensitization of [Ca2+]i
      mobilization was in a time and dose dependent manner and reached a plateau after
      3 hr. After 1 and 3 hr 5-HT pretreatment, 5-HT concentration in the medium little
      changed. 5-HT pretreatment with cycloheximide, a protein synthesis inhibitor,
      produced an enhancement of the desensitization for 3 and 6 hr pretreatment.
      However, 5-HT pretreatment for 3 and 6 hr caused no marked change in the 5-HT2A
      receptor mRNA level or Galphaq/11 protein in this study, suggesting that 5-HT may
      decrease 5-HT-induced [Ca2+]i mobilization independent of 5-HT2A receptor mRNA or
      G-proteins. Endothelin-1-induced [Ca2+]i mobilization did not alter after 5-HT
      and/or cycloheximide pretreatment. These results showed that activation of the 5
      HT2A receptor induced homologous desensitization and pretreatment with 5-HT
      and/or cycloheximide did not change the efficacy of the second messenger pathway
      from Gq to a [Ca2+]i rise.

PMID- 11341475
TI  - Tolterodine: a review of its use in the treatment of overactive bladder.
AB  - Tolterodine is a competitive muscarinic receptor antagonist that shows in vivo
      selectivity for the bladder over the salivary glands compared with oxybutinin.
      Results of randomised double-blind placebo-controlled studies indicate that
      tolterodine 4 mg/day (administered as immediate-release tablets 2mg twice daily
      or extended-release capsules 4mg daily) is superior to placebo in improving
      micturition diary variables in patients with overactive bladder. Moreover,
      tolterodine 2mg twice daily is as effective as oxybutynin 5mg 3 times daily.
      Maximum treatment effects with both drugs occurred after 5 to 8 weeks of
      treatment and improvements were maintained during long term treatment for up to
      24 months. In a pooled analysis of four 12-week studies, equivalent and
      significant reductions in micturition frequency (-2.3 and -2.0 vs -1.4, p <
      0.001) and the incidence of urge incontinence episodes (-1.6 and -1.8 vs -1.1, p
      < 0.05) were reported for tolterodine 2mg twice daily and oxybutynin 5mg 3 times
      daily compared with placebo. Functional bladder capacity was also significantly
      increased. Improvements in patient perceptions of their urgency symptoms and of
      problems caused by their bladder condition were significantly greater during
      treatment with tolterodine than with placebo. Tolterodine was generally well
      tolerated in clinical trials of up to 24 months' duration. Dry mouth was the most
      frequent adverse event. The incidence (40 vs 78%, p < 0.001) and intensity of
      this event was lower with tolterodine 2mg twice daily than oxybutynin 5mg 3 times
      daily. Additionally, a 23% lower incidence of dry mouth was reported with once
      daily extended-release tolterodine capsules than with twice daily immediate
      release tablets (p < 0.02). The incidence of adverse CNS events with tolterodine
      was low and similar to that of placebo. Tolterodine was well tolerated in elderly
      patients and no serious tolerability concerns were identified. CONCLUSION:
      Tolterodine is the first antimuscarinic agent to specifically developed for the
      treatment of overactive bladder. The functional selectivity of tolterodine for
      the bladder translates into good efficacy and tolerability in patients, including
      the elderly, with overactive bladder. Tolterodine is as effective as oxybutynin
      in improving micturition diary variables but is associated with a significantly
      lower incidence and intensity of dry mouth. This favourable tolerability profile,
      together with sustained clinical efficacy during long term treatment, places
      tolterodine as valuable treatment for the symptoms of overactive bladder.

PMID- 11341477
TI  - Effects of dexmedetomidine after transient and permanent occlusion of the middle
      cerebral artery in the rat.
AB  - Increased sympathetic tone is a consequence of cerebral ischemia. Although the
      role of catecholamines in ischemic damage is still unclear, in some experimental
      ischemia models alpha2-adrenergic agonism has proved to be neuroprotective. In
      the present work we have compared the effects of transient and permanent middle
      cerebral artery occlusion (MCAO) on the infarct volume, and, also, examined
      whether a selective alpha2-adrenergic receptor agonist, dexmedetomidine (9
      microg/kg or 15 microg/kg i.v.), is able to reduce ischemic damage after
      transient or permanent MCAO in rats. Permanent MCAO led to a significantly larger
      infarct volume than transient occlusion (p < 0.05). The rats receiving the higher
      dose of dexmedetomidine were detectected to have smaller (statistically non
      significant) infarct volume in the cortex (30.9%) and in the striatum (20.3%)
      after transient occlusion. Additionally, dexmedetomidine caused significant
      variations in the physiological parameters.

PMID- 11341478
TI  - Sodium azide treatment decreases striatal and cortical concentrations of alpha
      tocopherol in rats.
AB  - Sodium azide (20mg/kgsc), given for a maximum of 3 days to rats, significantly
      decreased the alpha-tocopherol concentrations in the cortex on day 2 and in the
      striatum on day 3. In these brain regions the oxidized glutathione values showed
      30 to 36% (statistically not significant) elevation on day 3. Reduced glutathione
      levels were not altered. The observations suggest an important role for alpha
      tocopherol in the defense against azide induced free radicals probably including
      NO and lipid peroxide radicals.

PMID- 11341479
TI  - A consideration of the dopamine D2 receptor monomer-dimer equilibrium and the
      anomalous binding properties of the dopamine D2 receptor ligand, N-methyl
      spiperone.
AB  - Some discrepancies between experimental results with the two D2 antagonists N
      methyl spiperone (NMSP) and raclopride (RAC) have been observed. Among these are
      the observation that MK-801 increases NMSP binding but not RAC binding:
      pretreatment with reserpine increases RAC binding but decreases NMSP binding; and
      that the two ligands yield different values for Bmax. It has been observed that
      the D2 receptor can exist in both a monomer and dimer form and that a NMSP
      photolabel ligand binds primarily to the monomer form while a RAC-like photolabel
      ligand binds both. Using a model of the dimerization in which the equilibrium
      dissociation constant increases with increasing dopamine (DA) concentration, the
      free monomer concentration can be shown to go through a maximum value with
      increasing DA. Using this model with data from a baboon PET study, it can be
      shown that under certain conditions an increase in binding could be observed.
      Further research may show that there are clusters of D2 receptors forming
      oligomers with more than two receptors in which NMSP binds to more sites on
      clusters with fewer receptors. If increasing DA favors cluster with fewer
      receptors, an increase in NMSP binding sites may also occur under some
      circumstances with an increase in DA.

PMID- 11341480
TI  - Synchrony of rest tremor in multiple limbs in parkinson's disease: evidence for
      multiple oscillators.
AB  - Recent evidence points to involvement of central nervous system oscillators in
      Parkinson's disease (PD) rest tremor. It remains unknown whether one or multiple
      oscillators cause tremor in multiple limbs. Based on the prediction that multiple
      oscillators would cause low coherence even with similar average frequency, we
      studied 22 PD patients using accelerometers on multiple limbs. Records were
      digitized and spectral analysis was performed. Peak frequencies in the arms,
      legs, and chin were similar, indicating that biomechanical factors did not
      determine the frequency. Coherence between different axes of individual
      accelerometers and between different segments of the same limb was high. However,
      coherence between tremor in different limbs was low. There was no consistent
      pattern across patients of ipsi- vs. contralateral predominance of coherence.
      These data suggest that tremor in PD is generated by multiple oscillatory
      circuits, which operate on similar frequencies.

PMID- 11341481
TI  - No evidence of association between CAG expansions and essential tremor in a large
      cohort of Italian patients.
AB  - Essential tremor (ET) is one of the most common movement disorders. However the
      pathogenesis is as yet unknown, although a genetic cause has long been
      recognised. Clinical and molecular evidences suggested that the ET gene might
      contain a CAG expanded region. In a cohort of Italian ET patients Repeat
      Expansion Detection (RED) approach did not demonstrate large CAG expansions. We
      extended the study towards specific targets: the channel proteins hSKCa3 and
      CACNL1A4. Direct assessment of CAG stretches within these two genes did not
      demonstrate any CAG expansion in affected subjects. Also a case-control analysis
      failed to reveal any evidence of association, thus excluding these genes as a
      cause of ET.

PMID- 11341482
TI  - No evidence of association between the D10S1423 locus and Alzheimer disease in
      Brazilian patients.
AB  - In a genome survey for Alzheimer's disease (AD), Zubenko et al. (1998) reported
      that the 234bp allele of the D10S1423 locus was more frequent among AD cases than
      in controls. We have analyzed this polymorphic locus in patients and healthy
      controls and observed that the 226bp allele is the most frequent allele in the
      D10S1423 locus in Brazilian AD patients. However, no statistically significant
      association between any D10S1423 allele was observed in AD patients as well as in
      controls.

PMID- 11341483
TI  - Brain monoamine receptors in a chronic unpredictable stress model in rats.
AB  - Antidepressant drugs are devoid of mood-elevating effects in normal (non
      depressed) human subjects, thus, it is necessary to evaluate the antidepressant
      property of compounds (drugs) in animal models of depression. Several animal
      models of depression have been introduced, however, only a few have been
      extensively validated. In the present study we report the results of
      investigations into monoaminergic receptors in the brain of rats subjected to
      chronic unpredictable stress (CUS) procedure (one of the well validated animal
      models of depression). We have examined the dopaminergic (D-1, D-2), adrenergic
      (alpha-1, beta-1) and serotonergic (5HT-1A, 5HT-2A) receptors in different brain
      regions by a saturation radioligand binding method in rats subjected to CUS
      paradigm and control animals. CUS procedure resulted in a significant 29%
      increase in the D-1 receptor density in the limbic system and 52% increase of the
      density of 5HT-2A receptors in the cerebral cortex. The present data indicate
      that the increase of the density of brain D-1 and 5HT-2A receptors of rats
      subjected to CUS might be involved in the pathophysiology of "animal depression"
      (since chronic antidepressant treatment produced opposite changes i.e. decrease
      in the density of these receptors) and thus in pathophysiology of human
      depression.

PMID- 11341484
TI  - Effects of lithium on dopamine D2 receptor expression in the rat brain striatum.
AB  - Effects of lithium on the dopamine D2 receptor expression in the rat brain
      striatum were studied. Feeding the chow containing 0.2% LiCO3 for 6 days
      increased the level of the dopamine D2 receptor mRNA, and the transcription rate
      of the dopamine D2 receptor gene, indicating the stimulatory effects of lithium
      on the transcription of the dopamine D2 receptor gene. [3H] Spiperone binding to
      the striatal membranes increased in the rats treated with lithium, while the
      Western blotting analysis showed no change of the amount of the dopamine D2
      receptors. These results suggested that lithium might induce the conformational
      changes of the dopamine D2 receptors. The methamphetamine-induced locomotor
      activity was enhanced by the pretreatment with lithium, whereas simultaneous
      increase in the methamphetamine concentration in the striatum was also observed.
      These observations suggested that the stimulation of methamphetamine-induced
      locomotor activity by lithium might be, at least partly, due to either increased
      sensitivity of the dopamine receptors, or increased concentration of
      methamphetamine in brain, or combination of both.

PMID- 11341485
TI  - Changes in the cAMP-related signal transduction mechanism in postmortem human
      brains of heroin addicts.
AB  - Immunoreactivities of adenylyl cyclase (AC) type I (AC-I), and basal, forskolin-
      and Mn2+-stimulated AC activities with or without calcium and calmodulin
      (Ca2+/CaM) were estimated in temporal cortex (TC)-and nucleus accumbens (NAc)
      membranes from brains of heroin addicts and controls. Immunoreactivity of AC-I
      was significantly decreased in TC from brains of heroin addicts, but that did not
      change in NAc. Ca2+/CaM-sensitive AC activity was significantly lower in TC from
      brains of heroin addicts, but that activity in NAc did not show significant
      difference compared with the control. Some previous reports demonstrated that
      Ca2+/CaM-sensitive AC activity in membranes from postmortem human brain reflected
      the function of AC-I. Therefore, the downregulation of AC-I in TC plays an
      important role in the molecular mechanism of chronic opiate addiction in human
      brain.

PMID- 11341486
TI  - Long-term effects of tricyclic antidepressants on norepinephrine kinetics in
      humans.
AB  - The nature of the discrepancy between short-term pharmacokinetic data (hours) on
      the one hand and long-term pharmacodynamic effects and the clinical latency of
      therapeutic amelioration on the other hand by tricyclic antidepressants is still
      unclear. A relapsed sensibilization of neuronal, immunologic, and endocrinologic
      systems by changes in receptor sensitivity has been proposed. However, the
      discrepancy may have a strong influence on many aspects of antidepressive therapy
      in humans. The aim of our study was to demonstrate long-term pharmacodynamic
      effects by single-dose antidepressive treatment in humans by measuring heart rate
      parameters in response to neurochemical parameters. 25 young healthy probands,
      divided into three treatment groups (amitriptyline, n = 10; clomipramine, n = 10;
      placebo, n = 5), were challenged by a noradrenaline infusion test at baseline and
      one and 21 days after a single dose of antidepressant. Heart rate and blood
      pressure as well as plasma levels of antidepressants and of noradrenaline and
      adrenaline were measured in response to noradrenaline infusion test.
      Noradrenaline infusion rate to reach an increase in blood pressure of RR > 30
      mmHg was significantly decreased for both antidepressants on day 1. The same
      effect was true for the amitriptyline group on day 21. Furthermore, pretreated
      probands respond to antidepressants in a different way when compared to untreated
      probands. Like depressed patients under therapy they respond with a dramatic
      increase in sensitivity of the alphal-adrenergic receptor. We could demonstrate
      that the long-term pharmacodynamic effects have a strong influence on
      antidepressive therapy. A prolonged pharmacodynamic effect influences further
      clinical studies as well as our thinking about adverse drug effects. In clinical
      studies, washout periods may be to short to overcome the benefits of a previous
      medication. Adverse drug effects are often seen during periods when drugs were
      changed. The negative effect may be due to an additional effect of both
      medicaments.

PMID- 11341487
TI  - Decreased cerebrospinal fluid levels of beta-endorphin and ACTH in children with
      infantile spasms.
AB  - To investigate the pathophysiology of infantile spasms (IS), we measured the
      cerebrospinal fluid (CSF) levels of beta-endorphin (beta-EP), adrenocorticotropic
      hormone (ACTH), and corticotropin-releasing hormone (CRH) in 20 patients with IS,
      including 11 with the secondary form and 9 with the cryptogenic form of the
      disease. The findings were compared with those obtained in age-matched controls
      without neurologic disease. The CSF levels of beta-EP and ACTH were significantly
      lower in patients with IS than those in the controls. The CSF levels of CRH in
      patients with IS were lower, although, this trend was not significant. These
      reductions in the CSF levels of these neuropeptides could explain the impairment
      of the brain-adrenal axis in such patients. These results might support the
      hypothesis that, instead of originating from an increased abundance of CRH, which
      can act as a rapid and potent convulsant, some infantile seizures could be caused
      by an ACTH deficiency.

PMID- 11341488
TI  - Mutation profiling in haemophilia A.

PMID- 11341489
TI  - Rapid hemophilia A molecular diagnosis by a simple DNA sequencing procedure:
      identification of 14 novel mutations.
AB  - We here describe a simple, efficient DNA sequencing procedure for hemophilia A
      molecular diagnosis. In severe patients we first test for the presence of factor
      VIII gene intron 22 inversion using a recently described single-tube PCR method.
      In moderate, mild, or inversion-negative severe patients we systematically
      sequence the promoter, all exons and splice junctions of factor VIII gene.
      Specially designed primers allow amplification of 23 PCR products under the same
      salt conditions and thermocycling parameters. The whole sequencing procedure,
      from blood extraction to mutation identification, can be readily done within 42 h
      when using regular instruments or in just 14 h when using a high-throughput
      sequencer. Thus, this is a versatile and cost-effective strategy with little
      hands-on time requirements. Since its implementation we have identified mutations
      in 45/46 hemophilia A patients, 14 of which are novel. Once the genetic defect
      has been identified, accurate genetic counseling is then easily performed.

PMID- 11341490
TI  - Hemostatic risk factors and arterial thrombotic disease.

PMID- 11341491
TI  - Modeling human zymogen factor IX.
AB  - Modern theoretical techniques are employed to provide complete three dimensional
      structure for the zymogen and activated forms of human coagulation factors IX and
      IXa. These structures are fully calcium bound and equilibrated in an electrically
      neutral aqueous environment. The relationship of structure to mutational data is
      examined. We find that a substantial relative orientational change of the
      catalytic domain occurs on activation. Also, we find that the
      electrostatistically dipolar nature of the catalytic domain is substantially
      modified upon activation, with cleavage of the negatively charged activation
      peptide leaving behind a largely hydrophobic face in factor IXa. While the
      backbone atoms of the catalytic residues have little relative movement, nearby
      loops are found that do move. The presence or absence of these changes likely
      defines specificity.

PMID- 11341492
TI  - Acute pulmonary embolism: impact of selection bias in prospective diagnostic
      studies. ANTELOPE Study Group. Advances in New Technologies Evaluating the
      Localization of Pulmonary Embolism.
AB  - We evaluated selection bias in a prospective study of 1,162 consecutive patients
      with suspected pulmonary embolism. Of these, 983 were eligible, and 627 could
      actually be included. During two months extensive data were collected on all non
      included patients. Finally, our patient characteristics were compared with those
      of the PIOPED study (1990) and the study of Hull et al. (1994). Compared with
      included patients, the non-included patients had more often non-diagnostic V/Q
      scans (50% vs. 36%, p <0.01) and were more often already hospitalized (31% vs.
      22%, P = 0.04). The subgroup of patients not included due to refusal or inability
      to give informed consent (IC) was older (mean age 61 vs. 53 years, P <0.01), more
      often suffered from malignancies (26% vs. 11%, P <0.01) and frequently had non
      diagnostic V/Q scans (57%) as compared to included patients. In our study, 54% of
      all patients screened was eventually included versus 27% in the PIOPED study. In
      the PIOPED study patients who had contra-indications for pulmonary angiography
      were excluded, while in the study of Hull et al. those with inadequate
      cardiorespiratory reserve were excluded. In studies on new diagnostic
      technologies, patient selection bias does occur. The potential for such a
      selection bias should be taken into account when diagnostic strategies are
      devised to improve their generalizability and acceptability.

PMID- 11341493
TI  - Coumarins during pregnancy: long-term effects on growth and development of school
      age children.
AB  - Anticoagulation during pregnancy is complicated because of potential risks for
      mother and foetus. Unfractionated or low-molecular-weight heparin is used for
      most anticoagulant indications. Its efficacy, however, in pregnant women with
      prosthetic heart valves is questioned, therefore coumarins are preferred for this
      indication. We studied long-term effects of prenatal coumarin-exposure on growth
      and on neurological, behavioural and cognitive development in 274 school-age
      children in comparison with 231 age-matched non-exposed controls. No major
      abnormalities were found. The exposed children had an increased risk for minor
      neurological dysfunction and for a low intelligence quotient (IQ below 80). The
      risk for a combination of two or more (minor) abnormalities was higher for the
      exposed children, RR = 7.6. We conclude that prenatal exposure to coumarins is
      associated with an increased risk for disturbances in development in school-age
      children. However, for the vast majority of children there is no clinical
      significant effect on growth and long-term development.

PMID- 11341494
TI  - Measurement of activated protein C resistance during menstrual cycle in women
      with and without the Leiden mutation.
AB  - Variations in the APC ratio during the menstrual cycle were assessed in 25 women
      without the Leiden mutation, and 10 women who were carrier of the mutation. Blood
      samples were collected at four occasions during one menstrual cycle. APC ratios
      were measured with two APTT based plasma methods with and without factor V
      depleted plasma. None of the methods were able to accurately discriminate between
      mutated and non mutated women in all samples. Although a normalized method with
      factor V depleted plasma was favorable. The levels of estradiol and progesterone
      did not differ between mutated and non mutated women. Our findings suggest that
      the level of estradiol at estimated time of ovulation is of importance for the
      response to APC during luteal phase, since the women exhibiting the highest
      levels of estradiol at time for ovulation had the lowest response to APC.

PMID- 11341495
TI  - Effects of oral and transdermal estrogen replacement therapy on markers of
      coagulation, fibrinolysis, inflammation and serum lipids and lipoproteins in
      postmenopausal women.
AB  - We compared the effects of oral estradiol (2 mg), transdermal estradiol (50
      microg), and placebo on measures of coagulation, fibrinolysis, inflammation and
      serum lipids and lipoproteins in 27 postmenopausal women at baseline and after 2
      and 12 weeks of treatment. Oral and transdermal estradiol induced similar
      increases in serum free estradiol concentrations. Oral therapy increased the
      plasma concentrations of factor VII antigen (FVIIag) and activated factor VII
      (FVIIa), and the plasma concentration of the prothrombin activation marker
      prothrombin fragment 1+2 (F1+2). Oral but not transdermal estradiol therapy
      significantly lowered plasma plasminogen activator inhibitor-1 (PAI-1) antigen
      and tissue-type plasminogen activator (tPA) antigen concentrations and PAI-1
      activity, and increased D-dimer concentrations, suggesting increased
      fibrinolysis. The concentration of soluble E-selectin decreased and serum C
      reactive protein (CRP) increased significantly in the oral but not in the
      transdermal or placebo groups. In the oral but not in the transdermal or placebo
      estradiol groups low-density-lipoprotein (LDL) cholesterol, apolipoprotein B and
      lipoprotein (a) concentrations decreased while high-density-lipoprotein (HDL)
      cholesterol, apolipoprotein AI and apolipoprotein All concentrations increased
      significantly. LDL particle size remained unchanged. In summary, oral estradiol
      increased markers of fibrinolytic activity, decreased serum soluble E-selectin
      levels and induced potentially antiatherogenic changes in lipids and
      lipoproteins. In contrast to these beneficial effects, oral estradiol changed
      markers of coagulation towards hypercoagulability, and increased serum CRP
      concentrations. Transdermal estradiol or placebo had no effects on any of these
      parameters. These data demonstrate that oral estradiol does not have uniformly
      beneficial effects on cardiovascular risk markers and that the oral route of
      estradiol administration rather than the circulating free estradiol concentration
      is critical for any changes to be observed.

PMID- 11341496
TI  - Platelet glycoprotein receptor IIIa polymorphism PLA1/PLA2 and coronary risk: a
      meta-analysis.
AB  - Membrane glycoprotein IIb/IIIa plays a major role in platelet function. The gene
      encoding the glycoprotein IIIa shows a common polymorphism PLA1/PLA2 that was
      variably associated with vascular disease. To clarify the role of PLA1/PLA2
      polymorphism in coronary risk, a meta-analysis of published data was conducted.
      Studies were identified both by MEDLINE searches, and hand searching of journals
      and abstract books. A total of 34 studies for coronary artery disease (CAD), and
      6 for restenosis after revascularization were identified, for a total of 9,095
      cases and 12,508 controls. In CAD, the overall odds ratio for carriers of the
      PLA2 allele was 1.10 (95% CI: 1.03 to 1.18), and it was 1.21 (95% CI: 1.05 to
      1.38) in subjects younger than 60. Overall odds ratio was 1.31 (95% CI: 1.10 to
      1.56) after revascularization procedures. The association of PLA2 status with
      overall cardiovascular disease in the general population is significant but weak;
      higher risk has been identified in less heterogeneous subgroups as in the younger
      cohorts and in the restenosis subset with stents.

PMID- 11341497
TI  - Standardisation of factor VIII and von Willebrand factor in plasma: calibration
      of the 4th International Standard (97/586).
AB  - The 4th International Standard (IS) Factor VIII/von Willebrand Factor (FVIII/VWF)
      plasma was calibrated in 25 laboratories by assay against the 3rd IS plasma and
      fresh normal plasma pools. Five parameters were measured, FVIII:coagulant
      activity (FVIII:C), FVIII:Antigen (FVIII:Ag), VWF:Antigen (VWF:Ag),
      VWF:Ristocetin Cofactor (VWF:RCof), and a new parameter, VWF:collagen binding
      (VWF:CB). Mean potency estimates for the 4th IS, calculated relative to the 3rd
      IS, were significantly greater than the mean estimates calculated relative to the
      fresh normal pools by 15, 14 and 20% respectively for FVIII:C, VWF:Ag and
      VWF:RCof. These results indicate a drift in the International Unit away from the
      fresh plasma unit. Partial rectification of this drift was achieved by assigning
      the mean of the estimates calculated relative to the 3rd IS and the fresh plasma
      pools, i.e. FVIII:C 0.57 IU/ampoule, VWF:Ag 0.79 IU/ampoule and VWF:RCof 0.73
      IU/ampoule. This represents a shift in the IU between the 3rd and 4th IS of 7.5%
      for FVIII:C, 7% for VWF:Ag and 10% for VWF:RCof. Mean estimates of FVIII:Ag
      relative to the 3rd IS and the fresh normal pools agreed to give an assigned
      value of 0.89 IU/ampoule. Excessive inter-laboratory variability and a low number
      of estimates (n = 6) precluded the assignment of a potency for VWF:CB. The 4th IS
      Factor VIII/VWF plasma (97/586) was established in October 1998.

PMID- 11341498
TI  - Cell-derived microparticles circulate in healthy humans and support low grade
      thrombin generation.
AB  - We determined the numbers, cellular origin and thrombin-generating properties of
      microparticles in healthy individuals (n = 15). Microparticles, isolated from
      fresh blood samples and identified by flow cytometry, originated from platelets
      [237 x 10(6)/L (median; range 116-565)], erythrocytes (28 x 10(6)/L; 13-46),
      granulocytes (46 x 10(6)/L; 16-94) and endothelial cells (64 x 10(6)/L; 16-136).
      They bound annexin V, indicating surface exposure of phosphatidylserine, and
      supported coagulation in vitro. Interestingly, coagulation occurred via tissue
      factor (TF)-independent pathways, because antibodies against TF or factor (F)VII
      were ineffective. In contrast, in our in vitro experiments coagulation was
      partially inhibited by antibodies against FXII (12%, p = 0.006), FXI (36%, p
      <0.001), FIX (28%, p <0.001) or FVIII (32%, p <0.001). Both the number of annexin
      V-positive microparticles present in plasma and the thrombin-generating capacity
      inversely correlated to the plasma concentrations of thrombin-antithrombin
      complex (r = -0.49, p = 0.072 and r = -0.77, p = 0.001, respectively), but did
      not correlate to prothrombin fragment F1+2 (r = -0.002, p = 0.99). The inverse
      correlations between the number of microparticles and their thrombin-forming
      capacity and the levels of thrombin-antithrombin complex in plasma may indicate
      that microparticles present in the circulation of healthy individuals have an
      anticoagulant function by promoting the generation of low amounts of thrombin
      that activate protein C. We conclude that microparticles in blood from healthy
      individuals support thrombin generation via TF- and FVII-independent pathways,
      and which may have an anticoagulant function.

PMID- 11341499
TI  - Prothrombin time ratio is reduced by magnesium contamination in evacuated blood
      collection tubes.
AB  - Magnesium ions were detected in sodium citrate solutions in several lots of
      evacuated blood collection tubes. The mean concentrations ranged between 1.3 and
      1.6 mmol/L. Magnesium was also present in the rubber stoppers of the blood
      collection tubes and could be leached into the citrate solution. It was shown
      that magnesium added to citrated plasma shortened the prothrombin time of both
      coumarin and normal plasma. The effect of magnesium was relatively greater on
      coumarin than on normal plasma resulting in reduced prothrombin time ratio.
      Shortening of the prothrombin time was also observed when magnesium chloride was
      added to dialysed plasma, i.e., in the absence of citrate. These results indicate
      that magnesium contamination can interfere with accurate INR determination in the
      control of oral anticoagulant therapy.

PMID- 11341500
TI  - Prothrombin Scranton: substitution of an amino acid residue involved in the
      binding of Na+ (LYS-556 to THR) leads to dysprothrombinemia.
AB  - Several members of a family from Scranton, Pennsylvania were identified to have
      normal levels of prothrombin antigen while their prothrombin clotting activity
      was approximately 50% of normal. There has been no previous history of bleeding
      or other clinical manifestations in this family. The genomic DNA from the proband
      was amplified for all exons in the prothrombin gene and analyzed by single strand
      conformation polymorphism (SSCP)/heteroduplex analysis followed by DNA sequence
      analysis and restriction enzyme digestion. A mutation at nucleotide 20040 in exon
      14 was identified and confirmed by restriction enzyme digestion. This mutation
      results in the substitution of Thr for Lys at amino acid 556. Amino acid 556 has
      been reported as one of the key residues for the binding of Na+ in the thrombin
      portion of the protein.

PMID- 11341501
TI  - Protein Z circulates in plasma in a complex with protein Z-dependent protease
      inhibitor.
AB  - Protein Z (PZ) is a vitamin K-dependent plasma protein that forms a Ca++
      dependent complex with factor Xa at phospholipid surfaces. This interaction
      between PZ and factor Xa enhances by >1,000-fold the inhibition of factor Xa by
      the serpin called protein Z-dependent protease inhibitor (ZPI). These experiments
      show that PZ also binds ZPI in a process that does not require Ca++ or
      phospholipids. In pooled normal plasma, which contains excess ZPI relative to PZ,
      all the PZ appears to be bound in a complex with ZPI. The binding of PZ to ZPI
      reduces the rate and extent of factor XIa inhibition produced by ZPI. During the
      course of these studies, it was noted that a PZ purification procedure, that
      included NaSCN (2.0 M) elution of PZ from an immunoaffinity column, produced
      aggregated, inactive forms of PZ.

PMID- 11341502
TI  - Thrombin activatable fibrinolysis inhibitor (TAFI) does not inhibit in vitro
      thrombolysis by pharmacological concentrations of t-PA.
AB  - TAFI (thrombin activatable fibrinolysis inhibitor) is a plasma
      procarboxypeptidase that upon activation inhibits the fibrinolytic process by
      removing the C-terminal lysines from partially degraded fibrin. The generation of
      activated TAFI (TAFIa) has been suggested to represent a mechanism of thrombus
      resistance to thrombolytic therapy. However, the ability of TAFI to inhibit
      fibrinolysis by pharmacological concentrations of t-PA has not been properly
      investigated. We used an in vitro model consisting of 125I-fibrin blood clots
      submerged in autologous defibrinated plasma. Upon addition of t-PA (125-5,000
      ng/ml) and CaCl2 (25 mM), samples were incubated at 37 degrees C, and clot lysis
      was measured at intervals from the radioactivity released into solution. The role
      of TAFI was assessed either by neutralizing the generated TAFIa with the specific
      inhibitor PTI (50 microg/ml) or by enhancing TAFI activation through the addition
      of recombinant soluble thrombomodulin (solulin, 1 microg/ml). In our clot lysis
      model, activation of TAFI amounted to about 20% of inducible carboxypeptidase
      activity. Addition of PTI, however, produced a significant increase in the extent
      of lysis only at concentrations of t-PA equal to or lower than 250 ng/ml. When
      solulin was added to the plasma surrounding the clot, about 70% of TAFI was
      activated within 15 min. Under these conditions, inhibition of clot lysis was
      very marked in samples containing 125 or 250 ng/ml of t-PA, but negligible in
      those containing pharmacological concentrations of the activator (1,000 and 5,000
      ng/ml). Additional experiments suggest that loss of fibrin-dependence by elevated
      concentrations of t-PA may be one of the mechanisms explaining the lack of effect
      of TAFIa. Our data indicate that, under our experimental conditions, clot lysis
      by pharmacological concentrations of t-PA is not influenced by TAFIa even after
      maximal activation of this procarboxy-peptidase.

PMID- 11341503
TI  - Low levels of thrombin activatable fibrinolysis inhibitor (TAFI) in patients with
      chronic liver disease.
AB  - Thrombin Activatable Fibrinolysis Inhibitor (TAFI) is a 60 kappaD glycoprotein
      present in plasma that regulates fibrinolysis by limiting the amount of fibrin
      available for fibrinolysis by tissue plasminogen activator (t-PA). Chronic liver
      disease is well-known to be associated with a low-grade fibrinolytic syndrome
      that under the appropriate stimulus proceeds to an overt disseminated
      intravascular coagulopathy (DIC) with demonstrable bleeding. In the present
      study, TAFI activity was measured in the plasma of 74 patients with advanced
      liver disease, and the levels of TAFI were related to those of other important
      coagulation and fibrinolytic factors. TAFI levels were very low and essentially
      undetectable in the plasma of patients with advanced hepatocellular liver
      disease. No relationship with the degradation products of fibrin was evident.

PMID- 11341504
TI  - The Fibrin Assay Comparison Trial (FACT): evaluation of 23 quantitative D-dimer
      assays as basis for the development of D-dimer calibrators. FACT study group.
AB  - Although D-dimer has gained widespread clinical use as a parameter for detection
      of in vivo fibrin formation, the issue of standardization of D-dimer assays
      remains to be resolved. The FACT study was performed to generate basic data for
      development of calibrators and standard preparations. A set of 86 samples,
      including plasma samples from patients with DIC, DVT. and other clinical
      conditions, serial dilutions of pooled plasma samples, and plasma samples
      containing fibrinogen- and fibrin derivatives, were distributed to 12
      manufacturers of D-dimer assays. D-dimer assays differ concerning specificity for
      crosslinked fibrin, and preference for either high molecular weight fibrin
      complexes, or low molecular weight fibrin degradation products. Terminal plasmin
      digests of fibrin clots for calibration produce aberrant results in some assays,
      especially those with preference for high molecular weight crosslinked fibrin
      derivatives. The best conformity is achieved by the use of pooled plasma samples
      from patients with high levels of D-dimer antigen in plasma. In vitro
      preparations containing a comparable composition of fibrin derivatives to
      clinical plasma samples may also serve as reference material.

PMID- 11341505
TI  - Fc-receptor dependent platelet aggregation induced by monoclonal antibodies
      against platelet glycoprotein Ib or von Willebrand factor.
AB  - In this paper we describe two pathways leading to platelet activation by
      crosslinking glycoprotein (GP) Ibalpha to the platelet Fc-receptor (FcgammaRII).
      First the monoclonal antibody (MoAb) 9C8, raised against human platelet
      GPIbalpha, dose-dependently induced platelet aggregation of citrate
      anticoagulated platelet-rich plasma, an effect that can be inhibited by several
      activation inhibitors. The FcgammaRII-inhibitory MoAb IV.3 was able to prevent
      the aggregatory effects of MoAb 9C8, indicating that crosslinking of the antigen
      GPIbalpha to the FcgammaII-receptor is necessary for the activating effect.
      Secondly we observed a synergistic activating effect of two anti-von Willebrand
      factor (vWF) MoAbs IC1E7 and B724, both known to enhance vWF binding to GPIbalpha
      in the presence of shear or ristocetin. When these antibodies are added together
      to PRP, platelet aggregation is induced without further need for an additional
      modulator. This effect can be blocked by either MoAb IV.3 or an inhibitory anti
      GPIb MoAb, indicating that again the platelet activation results from signaling
      through FcgammaRII crosslinked to vWF bound to GPIbalpha. In addition, both the
      anti-GPIb MoAb 9C8, or the two anti-vWF MoAbs 1C1E7 and B724 induce genuine
      platelet activation, as evidenced by the secretion of ATP and protein tyrosine
      phosphorylation. These findings with both anti-GPIb and anti-vWF MoAbs add
      further proof to recent reports demonstrating an interaction between the platelet
      receptors GPIb and FcgammaRII, suggesting a role for the FcgammaII-receptor in
      GPIb-related signaling.

PMID- 11341506
TI  - Binding of recombinant apolipoprotein(a) to human platelets and effect on
      platelet aggregation.
AB  - The interaction of lipoprotein(a) [Lp(a)] with platelets is not well defined,
      particularly with regards to the individual contribution of the protein
      components of Lp(a), the apo B-100 and the apolipoprotein apo(a). This study
      investigated the binding of different recombinant apo(a) [r-apo(a)] isoforms, to
      human platelets and its effect on platelet aggregation. Scatchard analysis of
      saturation binding experiments demonstrated that human platelets display a single
      class of high affinity r-apo(a) binding sites (71 +/- 46 molec./platelet, Kd =
      5.6 +/- 2.0 nmol/L). Platelet activation with strong agonists (thrombin,
      arachidonic acid) increased 2- to 10-fold the r-apo(a) binding, without affecting
      the affinity. Competition assays showed that the binding sites are highly
      specific for r-apo(a) and Lp(a). At high concentration t-PA could also bind to
      the r-apo(a) binding sites. By contrast, neither fibrinogen nor plasminogen
      inhibited to the r-apo(a) binding. The lysine analogue EACA inhibits the binding
      of r-apo(a) to platelets, thus suggesting the involvement of lysine residues in
      that interaction. Moreover, the r-apo(a) binding to platelets is unlikely
      mediated by GPIIb/IIIa-attached fibrin since it is not affected by platelet
      treatment with either LJ-CP8, a monoclonal antibody that specifically blocks
      fibrinogen binding to GPIIb/IIIa, nor GPRP, an inhibitor of fibrin
      polymerisation. Finally, we show that the distinct recombinant apo(a) proteins,
      as well as native Lp(a), promote an aggregation response of platelets to
      otherwise subaggregant doses of arachidonic acid. This proaggregant effect of r
      apo(a) is dependent on its binding to platelets since it requires a minimum
      incubation time, and it is prevented by EACA at concentration inhibiting the r
      apo(a)-platelet interaction. These results suggest that the prothrombotic action
      of Lp(a) may be in part mediated by modulating the platelet function through the
      interaction of its apo(a) subunit with a specific receptor at the platelet
      surface.

PMID- 11341507
TI  - Differential involvement of the P2Y1 and P2YT receptors in the morphological
      changes of platelet aggregation.
AB  - The relative contributions of the P2Y1 and P2YT receptors to the morphological
      changes induced in platelets by ADP or ADP-releasing agonists were assessed using
      two P2 antagonists, A2P5P and AR-C67085, selective for P2Y1 and P2YT,
      respectively. The P2Y1 receptor was found to be involved in i) the centralization
      of secretory granules elicited by ADP, ii) the formation of filopodia induced by
      released ADP in weakly activated platelets and iii) actin polymerization and the
      cytoskeletal translocation of cdc42, rac1 and rhoA, in an integrin alphaIIbbeta3
      dependent manner, in ADP-stimulated platelets. In contrast, the P2YT receptor was
      shown i) to be essential for the formation of stable macroaggregates, ii) to
      enhance actin polymerization and the cytoskeletal translocation of small GTPases,
      probably through amplification of platelet aggregation, and iii) not to be
      involved in the early steps of platelet activation since its blockade did not
      affect the cytoskeletal translocation of rhoA.

PMID- 11341508
TI  - Studies on the binding of 3H-SR121566, an inhibitor of Gp IIb-IIIa activation.
AB  - SR121566 is a new synthetic agent which inhibits the binding of fibrinogen to
      activated platelets, and platelet aggregation. 3H-SR121566 bound with nanomolar
      affinity (KD ranging from 45 to 72 nM) to Gp IIb-IIIa expressing cells only. On
      activated human platelets, this ligand allowed the detection of a maximal number
      of 100-140,000 binding sites. The binding of SR121566 to platelets, was displaced
      by several agents including RGD-containing peptides and synthetic RGD mimetics,
      but not by ReoPro, a humanised monoclonal antibody which inhibits the binding of
      fibrinogen to the Gp IIb-IIIa complex. Neither the fibrinogen dodecapeptide nor
      fibrinogen itself were able to compete with SR121566 whether platelets were
      activated or not. Flow cytometry studies indicated that SR121566 which did not
      activate Gp IIb-IIIa by itself, dose-dependently prevented the detection of
      activation-induced binding sites on TRAP-stimulated platelets in the presence or
      absence of exogenous fibrinogen, indicating a direct effect on the activation
      state of the Gp IIb-IIIa complex. Moreover, SR121566 was able to reverse the
      activation of Gp IIb-IIIa and to displace the binding of fibrinogen when added up
      to 5 min after TRAP stimulation of platelets. When added at later times (15 to 30
      min), SR121566 failed to displace fibrinogen binding, even if SR121566 binding
      sites were still accessible and the Gp IIb-IIIa complex not activated. In
      conclusion, our study is in accordance with the finding that fibrinogen is
      recognised by the activated Gp IIb-IIIa complex through the dodecapeptide
      sequence present on its gamma chain, and that this interaction is inhibited by
      SR121566 by preventing and reversing the activated conformation of Gp IIb-IIIa
      and not by direct competition with fibrinogen.

PMID- 11341509
TI  - Characterization of aspercetin, a platelet aggregating component from the venom
      of the snake Bothrops asper which induces thrombocytopenia and potentiates
      metalloproteinase-induced hemorrhage.
AB  - Thrombocytopenia occurs in a number of patients bitten by Bothrops asper, a
      species responsible for the majority of snakebites in Central America and
      southern Mexico. In this work we describe the isolation of a new platelet
      aggregating protein, named aspercetin, from the venom of B. asper, which induces
      thrombocytopenia in mice. Isolation was carried out by a combination of ion
      exchange chromatography on DEAE-Sepharose and affinity chromatography on Affi-Gel
      Blue. Aspercetin is a disulfide-linked heterodimer, with a pI of 4.5 and a
      molecular mass of 29,759 Da, detemined by MALDI-ESI mass spectrometry. N-terminal
      sequence shows homology with a number of venom proteins which belong to the C
      type lectin family. Aspercetin has functional similarities with botrocetin, from
      B. jararaca venom, since it induces platelet aggregation only in the presence of
      plasma or purified von Willebrand factor. Aspercetin-mediated platelet
      aggregation results from the interaction of von Willebrand factor with platelet
      receptor GPIb. Aspercetin lacks anticoagulant effect and does not agglutinate
      erythrocytes, in contrast with other representatives of the C-type lectin family
      isolated from snake venoms. Moreover, aspercetin is not lethal, nor does it
      induce myonecrosis, hemorrhage and edema. When injected intravenously or
      intramuscularly in mice it induces a rapid, dose-dependent drop in platelet
      counts and prolongs the bleeding time, suggesting that it may play a role in the
      thrombocytopenia that develops in a number of B. asper envenomations. Moreover,
      mice injected intravenously with aspercetin and then receiving an intradermal
      injection of B. asper hemorrhagic metalloproteinase BaP1 develop a larger
      hemorrhagic lesion than mice receiving only BaP1. This suggests that aspercetin,
      by reducing platelet numbers, may

PMID- 11341510
TI  - Evidence from site-directed mutagenesis that the cytoplasmic domain of the beta3
      subunit influences the conformational state of the alphaVbeta3 integrin
      ectodomain.
AB  - In order to explore the mechanisms leading to conformational changes of the
      vitronectin receptor alphavbeta3 following ligand or divalent cation binding, we
      have investigated the expression of epitopes known as ligand-induced binding
      sites (LIBS) on beta3 cytoplasmic tail mutants expressed in CHO cells. Truncation
      of the entire beta3 cytoplasmic domain induced constitutive LIBS exposure on
      alphavbeta3 and alphaIIbeta3. Deletion of the C-terminal NITY759 sequence or
      disruption of the NPLY747 motif by a Y747A substitution impaired extracellular
      conformational changes on alphavbeta3 following RGDS, echistatin or Mn2+ binding,
      whereas the substitutions Y747F, Y759A or Y759F allowed normal LIBS exposure.
      Furthermore, metabolic energy depletion totally prevented Mn2+-dependent LIBS
      exposure, but had only a minor effect on RGDS-induced conformational changes. Our
      results demonstrate that the structural integrity of the NPLY747 motif in the
      beta3 cytoplasmic domain, rather than potential phosphorylation of Tyr747 or
      Tyr759, is a prerequisite for conformational changes within the alphavbeta3
      ectodomain, and suggest that two different mechanisms are responsible for RGDS-
      and Mn2+-dependent conformational changes.

PMID- 11341511
TI  - N-acetyl-cysteine reduces neointimal thickening and procoagulant activity after
      balloon-induced injury in abdominal aortae of New Zealand white rabbits.
AB  - BACKGROUND: Procoagulant activity and oxidative stress generated by balloon
      injury to normal vessels promote the migration of medial smooth muscle cells and
      their proliferation in the intima. We hypothesised that administering levo N
      acetyl-cysteine (NAC) i.v. at the time of injury, and s.c. before and after
      injury would reduce neointimal formation 4 weeks later and would regulate
      procoagulant activity in vessels with neointima undergoing ballooning a second
      time. METHODS AND RESULTS: at the time of injury rabbits received: NAC,
      unfractionated heparin (HEP) or both (NAC + HEP). Neointimal thickening at 28
      days, calculated as the ratio between the intimal and medial area, was attenuated
      after NAC, HEP and NAC+HEP by 39%, 30% and 47% respectively when compared to
      untreated injured animals (CONTROLS) (p <0.05). At 28 days, bound thrombin
      activity and platelet adhesion 1 h after a repeated balloon injury decreased in
      animals receiving NAC, HEP and NAC+HEP bv 54%, 63% and 64% for thrombin activity
      (p <0.05 vs CONTROLS), and by 56%, 66% and 75% respectively for 111Indium
      platelet deposition (p <0.05 vs CONTROLS). CONCLUSIONS: NAC in-vivo was effective
      in reducing neointimal thickening and procoagulant response after balloon injury.

PMID- 11341512
TI  - High density lipoproteins induce cell cycle entry in vascular smooth muscle cells
      via mitogen activated protein kinase-dependent pathway.
AB  - In this study we found that HDL acts as a potent and specific mitogen in vascular
      smooth muscle cells (VSMC) by stimulating entry into S-phase and DNA synthesis in
      a time- and concentration-dependent manner, induction of cyclins D1, E, and A, as
      well as activation of cyclin D-dependent kinases as inferred from phosphorylation
      of the retinoblastoma protein (pRb). Moreover, HDL induced activation of the
      mitogen-activated protein kinase pathway including Raf-, MEK-1, and ERK1/2, as
      well as the expression of proto-oncogen c-fos, which is controlled by ERK1/2.
      PD98059, an inhibitor of MEK-1 blocked the mitogenic activity of HDL and cyclin
      D1 expression. HDL-induced VSMC proliferation, cell cycle progression, cyclin D1
      expression, and activation of the Raf-1/MEK-1/ERK1/2 cascade were blocked by
      preincubation of cells with pertussis toxin indicating involvement of trimeric G
      protein. By contrast, none of these responses was inhibited by the protein kinase
      C inhibitor, GF109203X. The mitogenic effects of native HDL were not mimicked by
      apo A-I, reconstituted HDL containing apo A-I, or cholesterol-containing
      liposomes. In conclusion, HDL possesses an intrinsic property to induce G-protein
      and MAP-kinase-dependent proliferation and cell cycle progression in VSMC. The
      strong and specific mitogenic effect of HDL should be taken into account, when
      therapeutic strategies to elevate the plasma level of these lipoproteins are
      developed.

PMID- 11341513
TI  - Absence of fibrinogen in afibrinogenemia results in large but loosely packed
      thrombi under flow conditions.
AB  - We studied the role of fibrinogen in platelet thrombus formation under flow on
      adhesive proteins using afibrinogenemic blood (LMWH anticoagulated) in a
      perfusion system. Perfusions with afibrinogenemic blood showed strong increased
      surface coverage and thrombus volume that normalized upon addition of fibrinogen.
      Similar studies using citrate anticoagulated blood showed that this was due to
      fibrinogen and not fibrin. Morphological analysis showed that afibrinogenemic
      thrombi were loosely packed and consisted mainly of dendritic platelets that
      contacted one another through filopodia. However, in the presence of fibrinogen,
      platelets formed lamellipodia and spread out on top of one another. Studies with
      radiolabeled platelets showed similar numbers of platelets in both conditions
      demonstrating that the difference is one of packing and the larger size is due to
      absence of lamellipodia formation and spreading. The found increased thrombus
      size and loosely packed platelets might help to understand thrombotic
      complications sometimes seen in afibrinogenemia patients.

PMID- 11341514
TI  - The blue toe syndrome during oral anticoagulant therapy with acenocoumarol.

PMID- 11341515
TI  - Should the D-dimer cut-off value be increased in elderly patients suspected of
      pulmonary embolism?

PMID- 11341516
TI  - The PLA1/A2 polymorphism of platelet glycoprotein IIIa is not associated with
      peripheral arterial disease.

PMID- 11341517
TI  - Factor VII polymorphisms and myocardial infarction: what is special in Italians?
      REGRESS study group. Regression Growth Evaluation Statin Study.

PMID- 11341518
TI  - A tail vein bleeding time model and delayed bleeding in hemophiliac mice.

PMID- 11341519
TI  - Combined fresh frozen plasma with recombinant factor VIIa in restoring hemostasis
      for invasive procedures in children with liver diseases.

PMID- 11341520
TI  - The endothelial protein C receptor (EPCR) 23bp insert in patients with myocardial
      infarction.

PMID- 11341521
TI  - The expression of exercise-induced tPA activity in blood is regulated by the
      basal level of PAI-1.

PMID- 11341522
TI  - Should a normal D-dimer rule out angiographic pulmonary embolism or unfavorable
      outcome in patients left untreated?

PMID- 11341523
TI  - Rebuttal to: Passive smoking adversely affects the haemostasis/fibrinolytic
      parameters in healthy non-smoker offspring of healthy smokers.

PMID- 11341524
TI  - Noise reduction in brain evoked potentials based on third-order correlations.
AB  - In this paper, we use third-order correlations (TOC) in developing a filtering
      technique for the recovery of brain evoked potentials (EPs). The main idea behind
      the presented technique is to pass the noisy signal through a finite impulse
      response filter whose impulse response is matched with the shape of the noise
      free signal. It is shown that it is possible to estimate the filter impulse
      response on basis of a selected third-order correlation slice (TOCS) of the input
      noisy signal. This is justified by two facts. The first one is that the noise
      free EPs can be modeled as a sum of damped sinusoidal signals and the selected
      TOCS preserve the signal structure. The second fact is that the TOCS is
      insensitive to both Gaussian noise and other symmetrically distributed non
      Gaussian noise, (white or colored). Furthermore, the approach can be applied to
      either nonaveraged or averaged EP observation data. In the nonaveraged data case,
      the approach therefore preserves information about amplitude and latency changes.
      Both fixed and adaptive versions of the proposed filtering technique are
      described. Extensive simulation results are provided to show the validity and
      effectiveness of the proposed cumulant-based filtering technique in comparison
      with the conventional correlation-based counterpart.

PMID- 11341525
TI  - An arrhythmia detector and heart rate estimator for overnight polysomnography
      studies.
AB  - We present an algorithm for automatic on-line analysis of the electrocardiography
      (ECG) channel acquired during overnight polysomnography (PSG) studies. The system
      is independent of ECG morphology, requires no manual initialization, and operates
      automatically throughout the night. It highlights likely occurrences of
      arrhythmias and intervals of bad signal quality while outputting a continual
      estimate of heart rate. Algorithm performance is validated against standard ECG
      databases and PSG data. Results demonstrate a minimal false negative rate and a
      low false positive rate for arrhythmia detection, and robustness over a wide
      range of noise contamination.

PMID- 11341526
TI  - A method for diagnosing multiple diseases in MUNIN.
AB  - A new method for diagnosing multiple diseases in large medical decision support
      systems based on causal probabilistic networks is proposed. The method is based
      on characteristics of the diagnostic process that we believe to be present in
      many diagnostic tasks, both inside and outside medicine. The diagnosis must often
      be made under uncertainty, choosing between diagnoses that each have small prior
      probabilities, but not so small that the possibility of two or more simultaneous
      diseases can be ignored. Often a symptom can be caused by several diseases and
      the presence of several diseases tend to aggravate the symptoms. For diagnostic
      problems that share these characteristic, we have proposed a method that operates
      in a number of phases: in the first phase only single diseases are considered and
      this helps to focus the attention on a smaller number of plausible diseases. In
      the second phase, pairs of diseases are considered, which make it possible to
      narrow down the field of plausible diagnoses further. In the following phases,
      larger subsets of diseases are considered. The method was applied to the
      diagnosis of neuromuscular disorders, using previous experience with the so
      called MUNIN system as a starting point. The results showed that the method gave
      large reductions in computation time without compromising the computational
      accuracy in any substantial way. It is concluded that the method enables
      practical inference in large medical expert systems based on causal probabilistic
      networks.

PMID- 11341527
TI  - A probabilistic solution to the MEG inverse problem via MCMC methods: the
      reversible jump and parallel tempering algorithms.
AB  - We investigated the usefulness of probabilistic Markov chain Monte Carlo (MCMC)
      methods for solving the magnetoencephalography (MEG) inverse problem, by using an
      algorithm composed of the combination of two MCMC samplers: Reversible Jump (RJ)
      and Parallel Tempering (PT). The MEG inverse problem was formulated in a
      probabilistic Bayesian approach, and we describe how the RJ and PT algorithms are
      fitted to our application. This approach offers better resolution of the MEG
      inverse problem even when the number of source dipoles is unknown (RJ), and
      significant reduction of the probability of erroneous convergence to local modes
      (PT). First estimates of the accuracy and resolution of our composite algorithm
      are given from results of simulation studies obtained with an unknown number of
      sources, and with white and neuromagnetic noise. In contrast to other approaches,
      MCMC methods do not just give an estimation of a "single best" solution, but they
      provide confidence interval for the source localization, probability distribution
      for the number of fitted dipoles, and estimation of other almost equally likely
      solutions.

PMID- 11341528
TI  - An acoustic model of the respiratory tract.
AB  - With the emerging use of tracheal sound analysis to detect and monitor
      respiratory tract changes such as those found in asthma and obstructive sleep
      apnea, there is a need to link the attributes of these easily measured sounds
      first to the underlying anatomy, and then to specific pathophysiology. To begin
      this process, we have developed a model of the acoustic properties of the entire
      respiratory tract (supraglottal plus subglottal airways) over the frequency range
      of tracheal sound measurements, 100 to 3000 Hz. The respiratory tract is
      represented by a transmission line acoustical analogy with varying cross
      sectional area, yielding walls, and dichotomous branching in the subglottal
      component. The model predicts the location in frequency of the natural acoustic
      resonances of components or the entire tract. Individually, the supra and
      subglottal portions of the model predict well the distinct locations of the
      spectral peaks (formants) from speech sounds such as /a/ as measured at the mouth
      and the trachea, respectively, in healthy subjects. When combining the
      supraglottic and subglottic portions to form a complete tract model, the
      predicted peak locations compare favorably with those of tracheal sounds measured
      during normal breathing. This modeling effort provides the first insights into
      the complex relationships between the spectral peaks of tracheal sounds and the
      underlying anatomy of the respiratory tract.

PMID- 11341529
TI  - Geometrical aspects of the interindividual variability of multilead ECG
      recordings.
AB  - The electrocardiogram (ECG) as measured from healthy subjects shows a
      considerable interindividual variability. This variability is caused by
      geometrical as well as by physiological factors. In this study, the relative
      contribution of the geometrical factors is estimated. In addition a method aimed
      at correcting for these factors is described. First, a measure (RV) for
      quantifying the overall variability is presented, and for healthy individuals its
      value is estimated as 0.52. Next, based on a simulation study using the
      individual (heart-lung-torso) geometry of 25 subjects, the variability caused by
      geometrical factors is estimated as 0.40, indicating that in healthy subjects the
      RV for healthy individuals resulting from electrophysiology is of the order of
      0.33. In an evaluation of the correction procedure, applied to realistic,
      simulated body surface potentials, it is shown that RV caused by geometrical
      factors can be reduced from 0.40 to 0.06. When applying the correction procedure
      to measured ECG data no reduction of the RV value could be demonstrated. These
      results indicate that the involved procedure of the inverse computation of a
      cardiac equivalent source, at the present time, is of insufficient quality to
      cash in on the substantial reduction of RV values from 0.52 down to 0.33 that
      might be obtainable.

PMID- 11341530
TI  - Quantitative three-dimensional analysis and diffusion modeling of oligonucleotide
      concentrations after direct intraparenchymal brain infusion.
AB  - We compared quantitative experimental results on the diffusion of 35S-labeled
      phosphorothioate oligonucleotide (PS-ODN) after intraparenchymal infusion in rat
      brain, with the distributions predicted by Fick's second law of diffusion.
      Fischer 344 rats underwent identical intracerebral infusions of 36S-PS-ODN. After
      0, 5, 11, 23, and 47 h, groups of animals were sacrificed and sequential brain
      cryosections subjected to autoradiography. The resulting experimental data were
      compared to the predicted distributions, for estimation of the apparent free
      diffusion coefficient, D*. Volumes of distribution and total content of 36 S-PS
      ODN in the parenchyma were also computed, to monitor loss of total material. The
      values for D* were within the expected range for the 21-mer PS-ODN used, but a
      progressive decrease in D* over time was noted. The model requires D* to remain
      constant and, thus, does not adequately explain the spread of 35S-PS-ODN
      following infusion. The progressive slowing of spread over time suggests that at
      later time points, 35S-PS-ODN may be fixed by tissue binding or cellular uptake
      in the brain. Loss of material via vascular and CSF clearance may also contribute
      to the lack of fit. Our results highlight issues to be addressed in the modeling
      and experimental design of the intraparenchymal infusion process.

PMID- 11341531
TI  - Handling individual mammalian embryos using microfluidics.
AB  - We have designed, built, and tested microfluidic systems capable of transporting
      individual, preimplantation mouse embryos (100-microm to 150-microm diameter)
      through a network of channels. Typical channels are 160 to 200 microm deep, 250
      to 400 microm wide at the top, and narrower at the bottom (0 to 250 microm wide)
      due to the fabrication process. In these channels, a pressure gradient of 1 Pa/mm
      causes the medium to flow on the order of 10(-10) m3/s (100 nl/s), with an
      average speed of 1 to 2 mm/s. Under these flow conditions the embryos roll along
      the bottoms of the channels, traveling at 1/2 the speed of the fluid. By
      manipulating the pressure at the wells connected to the ends of the channels, the
      embryos can be transported to (and retained at) specific locations including
      culture compartments and retrieval wells.

PMID- 11341532
TI  - Markov modeling of minimally invasive surgery based on tool/tissue interaction
      and force/torque signatures for evaluating surgical skills.
AB  - The best method of training for laparoscopic surgical skills is controversial.
      Some advocate observation in the operating room, while others promote animal and
      simulated models or a combination of surgery-related tasks. A crucial process in
      surgical education is to evaluate the level of surgical skills. For laparoscopic
      surgery, skill evaluation is traditionally performed subjectively by experts
      grading a video of a procedure performed by a student. By its nature, this
      process uses fuzzy criteria. The objective of the current study was to develop
      and assess a skill scale using Markov models (MMs). Ten surgeons [five novice
      surgeons (NS); five expert surgeons (ES)] performed a cholecystectomy and Nissen
      fundoplication in a porcine model. An instrumented laparoscopic grasper equipped
      with a three-axis force/torque (F/T) sensor was used to measure the
      forces/torques at the hand/tool interface synchronized with a video of the tool
      operative maneuvers. A synthesis of frame-by-frame video analysis and a vector
      quantization algorithm, allowed to define F/T signatures associated with 14
      different types of tool/tissue interactions. The magnitude of F/T applied by NS
      and ES were significantly different (p < 0.05) and varied based on the task being
      performed. High F/T magnitudes were applied by NS compared with ES while
      performing tissue manipulation and vise versa in tasks involved tissue
      dissection. From each step of the surgical procedures, two MMs were developed
      representing the performance of three surgeons out of the five in the ES and NS
      groups. The data obtained by the remaining two surgeons in each group were used
      for evaluating the performance scale. The final result was a surgical performance
      index which represented a ratio of statistical similarity between the examined
      surgeon's MM and the MM of NS and ES. The difference between the performance
      index value, for a surgeon under study, and the NS/ES boundary, indicated the
      level of expertise in the surgeon's own group. Using this index, 87.5% of the
      surgical procedures were correctly classified into the NS and ES groups. The
      12.5% of the procedures that were misclassified were performed by the ES and
      classified as NS. However in these cases the performance index values were very
      close to the NS/ES boundary. Preliminary data suggest that a performance index
      based on MM and F/T signatures provides an objective means of distinguishing NS
      from ES. In addition, this methodology can be further applied to evaluate haptic
      virtual reality surgical simulators for improving realism in surgical education.

PMID- 11341533
TI  - Light paths in retinal vessel oxymetry.
AB  - The oxygen utilization and, therefore, the metabolic state, of a distinctive area
      of the retina may be calculated from the diameter of the supplying artery and
      vein, the haemoglobin oxygenation, and the velocity of the blood. The first two
      parameters can be determined by imaging spectrometry at the patients ocular
      fundus. However, the reflected light emerging from a vessel followed different
      pathways through the ocular fundus layers and the vessel embedded in the retina.
      The contribution of the single pathways to the vessel reflection profile is
      investigated by a Monte Carlo simulation. Considering retinal vessels with
      diameters of 25-200 microm we found the reflection from a thin vessel to be
      determined by the single and double transmission of light at 560 nm. The
      backscattering from the blood column determines the reflectance in the case of a
      thick vessel. However, both components are in the same order of magnitude. This
      has to be considered in the calculation of the oxygen saturation of blood in
      retinal vessels from their reflection spectra.

PMID- 11341534
TI  - A 915-MHz antenna for microwave thermal ablation treatment: physical design,
      computer modeling and experimental measurement.
AB  - A 915-MHz antenna design that produces specific absorption rate distributions
      with preferential power deposition in tissues surrounding and including the
      distal end of the catheter antenna is described. The design features minimal
      reflected microwave current from the antenna flowing up the transmission line.
      This cap-choke antenna consists of an annular cap and a coaxial choke which
      matches the antenna to the coaxial transmission line. The design minimizes
      heating of the coaxial cable and its performance is not affected by the depth of
      insertion of the antenna into tissue. The paper provides a comparison of results
      obtained from computer modeling and experimental measurements made in tissue
      equivalent phantom materials. There is excellent agreement between numerical
      modeling and experimental measurement. The cap-choke, matched-dipole type antenna
      is suitable for intracavitary microwave thermal ablation therapy.

PMID- 11341535
TI  - Detection of delayed gastric emptying from electrogastrograms with support vector
      machine.
AB  - A recent study reported a conventional neural network (NN) approach for the
      noninvasive diagnosis of delayed gastric emptying from the cutaneous
      electrogastrograms. Using support vector machine, we show that this relatively
      new technique can be used for detection of delayed gastric emptying and is in
      fact able to outdo the conventional NN.

PMID- 11341536
TI  - Fast detection and characterization of vessels in very large 3-D data sets using
      geometrical moments.
AB  - An improved and very fast algorithm dealing with the extraction of vessels in
      three-dimensional imaging is described. The approach is based on geometrical
      moments and a local cylindrical approximation. A robust estimation of vessel and
      background intensity levels, position, orientation, and diameter of the vessels
      with adaptive control of key parameters, is provided during vessel tracking.
      Experimental results are presented for lower limb arteries in multidetector
      computed tomography scanner.

PMID- 11341537
TI  - A novel and simple technique to allow detection of the position of the R-waves
      from intraventricular pressure waveforms: application to the conductance catheter
      method.
AB  - A simple and novel technique that utilizes the zero-crossing points of the first
      time derivative of intra-ventricular pressure (dP/dt) to mark systole, is
      proposed. Discrete differentiation of the sampled pressure waveform is calculated
      using a difference equation. Filtration of high-frequency noise in dP/dt is
      achieved using a low-pass Butterworth filter of order 4 and a cutoff frequency of
      10 Hz. The filter is realized digitally using infinite impulse response filter
      stages. Double filtering of discrete dP/dt is used to eliminate time shifts. The
      methods are evaluated on data obtained from six large, white, anaesthetised and
      open chest pigs, instrumented with a conductance catheter. The zero-crossing
      points of the filtered dP/dt compare very well with the R-waves of the
      electrocardiogram (ECG) as markers of systole. The mean error is 1.3% of the
      duration of the heartcycle. Significantly, our results provide a solution to a
      problem often encountered with multiuse pressure-volume catheters when an ECG
      signal cannot be obtained. In this situation, the zero-crossing points of dP/dt,
      rather than the R-waves of the ECG, can be used as a marker of systole, thus
      enabling the construction of end-systolic pressure-volume relations to assess
      cardiac contractility.

PMID- 11341538
TI  - Comments on "Is accurate recording of the ECG surface Laplacian feasible?".

PMID- 11341539
TI  - In vivo studies of man-made mineral fibers--fibrosis-related factors.
AB  - Pneumoconiosis that pursues a chronic course may result from repeated injury and
      repair caused by dust particles that remain in the lungs, leading to fibrosis. We
      will introduce in vivo studies concerning these processes using animals exposed
      to man-made mineral fibers and asbestos. We will report on whether there are
      developmental changes with the mineral fiber and animal model in proinflammatory
      cytokine, chemokine, free radicals, proteinase and other genes that lead to
      injury, as well as in genes that effect repair such as growth factor, and we will
      also report on the effects of surfactant protein and clara cell secretory protein
      on fibrosis.

PMID- 11341540
TI  - Biopersistence of man-made fibers by animal inhalation experiments in recent
      reports.
AB  - Biopersistence of man-made fibers by animal inhalation experiments was mainly
      reviewed. This report showed that the biopersistence and maximum tolerated dose
      are significantly important factors for hazard assessment for man-made fibers as
      well as fiber size (diameter/length), chemical compositions and surface
      properties.

PMID- 11341541
TI  - Man-made respirable-sized organic fibers: what do we know about their
      toxicological profiles?
AB  - Man-made organic fibers (MMOFs) have been manufactured for over 50 years. Until
      recently, there have been few concerns raised regarding the safety of organic
      fiber dusts. This is due, in large part, to the perception that the dimensions of
      most, if not all, of these products were too large to be inhaled into the distal
      lungs of workers, i.e., were considered to be nonrespirable. A brief review of
      some of the issues related to organic fiber toxicology is presented herein. Some
      of the organic fiber-types used in commerce are identified and some fundamental
      tenets of fiber toxicology are discussed. In addition, the European Union, in
      their recent consideration for banning chrysotile asbestos fibers, evaluated some
      organic fiber substitutes and compared them to the hazards of asbestos. A brief
      review of their conclusions is described below. Finally, the results of some
      recent studies assessing the mechanisms of biodegradability of para-aramid
      respirable-sized, fiber-shaped particulates (RFP) are presented. Para-aramid (p
      aramid) RFP are the most extensively-studied respirable organic fiber-type and
      RFP is the new term which describes respirable-sized organic fibers (ECETOC,
      1996) (1). The results of these studies provide clues regarding the mechanism(s)
      of p-aramid RFP shortening in the lungs of exposed animals, and may be relevant
      for humans.

PMID- 11341542
TI  - The trend in airborne asbestos concentrations at plants manufacturing asbestos
      containing products in Japan.
AB  - In Japan, chrysotile is still permitted to use under the Ordinance on Prevention
      of Hazards due to Specified Chemical Substances. In recent years many countries
      have introduced a policy of prohibiting the use of asbestos, based on clinical
      and epidemiological studies. In light of this, it is important to evaluate the
      airborne asbestos concentrations in workplaces and also estimate the number of
      related disease cases in order to discuss the ban of asbestos use. The survey
      covered 528 workplaces in 145 plants and included 2795 asbestos handling workers
      from 1985 to 1998. These plants were belonging to the Japan Asbestos Association
      (JAA) as member companies. In Japan, nearly all of the asbestos using
      manufacturing companies are members of JAA. In our study, all of the workplaces
      were divided under each separate manufacturing process and classified into 3
      categories of Control Classes. Of the 454/528 (86.0%) workplaces classified as
      Control Class 1 are improved to 376/378 (99.5%). Though in the cases of small
      enterprises, other factors such as a shift in product lines, and the economic
      recession, as well as efforts, contributed to improvements in working conditions.
      JAA recommended self-administered concentrations of 1.0 f/ml (compatible to <0.3
      f/ml in personal exposure level) in 1991 to promote further improvements of the
      work environment. From this point of view, exposure limits can almost be
      technically achieved in Japan, and it is expected that asbestos related disease
      could be expected to decrease in 20 to 30 years later. This survey will become
      basic material for verifications whether we could control asbestos related
      diseases enough in such well-controlled work environment.

PMID- 11341543
TI  - Airborne fiber concentration and size distribution of mineral fibers in area with
      serpentinite outcrops in Aichi prefecture, Japan.
AB  - Airborne fiber concentrations and size distributions of both asbestos and
      nonasbestos fibers were determined at property boundaries of 4 serpentinite
      quarries producing crushed stone (quarry property boundary), 10 sites within 10
      km of the area with serpentinite outcrops (serpentinite area), and 2 sites in a
      reference area. The asbestos was identified in 7 rock and 3 soil samples
      collected in the serpentinite area. The geometric means of airborne
      concentrations of asbestos and nonasbestos fibers longer than 0.2 microm in
      length were: 384 and 447 fibers/liter (f/L) in the quarry property boundary (in
      operation), 12 and 124 f/L in the quarry property boundary (in closed), 5 and 103
      fibers/liter in the serpentinite area, and less than 2 and 59 fibers/liter in the
      reference area, respectively. There was a significant difference in airborne
      concentrations of both asbestos and nonasbestos fibers among the areas.
      Ttremolite/actinolite were found with chrysotile in the stones. Airborne
      concentrations of tremolite/actinolite were higher than those of chrysotile at
      the quarry property boundary and in the serpentinite area. Tremolite/actinolite
      were also found in the soils. There was no significant difference among the areas
      in the arithmetic means of fiber size distribution of both asbestos and
      nonasbestos fibers.

PMID- 11341544
TI  - Estimation of fibrous aerosol deposition in upper bronchi based on experimental
      data with model bifurcation.
AB  - Lung deposition of fibrous aerosol was studied by using a model of the lung
      bifurcation with dimensions based on the symmetric model A of Weibel. The fibrous
      aerosols were introduced to the model under steady inspiratory flow conditions.
      Glass fibers depositing in the daughter tubes and these escaping from them were
      observed under a scanning electron microscope (SEM). The deposited fractions were
      calculated for each length and diameter using a bivariate lognormal distribution.
      In this study the authors propose empirical equations to estimate total deposited
      fractions of fibrous aerosol at upper bronchi. The dimensionless relationship
      among deposited fractions Fd, Stokes number St for randomly-oriented fibers and
      interception parameter I were used to estimate the deposited fraction at
      arbitrary position in the upper bronchi. The calculation procedure for Fd(St,I)
      consists of two steps: the determination of the four deposited fractions, Fdn for
      each In (n=1-4) followed by interpolation or extrapolation from Fdn to find the
      deposited fraction Fd at a given I. With this procedure, it is possible to
      determine the deposited fraction Fd in the range of 2 x 10(-3)<St<5 x 10(-2) and
      5 x 10(-4)<I<5 x 10(-2). Penetration from the trachea to the 10th generation of
      lung bifurcation was calculated for several cases of fiber diameter, length and
      flow rate. In the case corresponding to an inspiration of 500 cm3 air at a
      constant rate for 2 s, more than half of the fibers with a length of 100 microm
      and diameter of 3 microm are deposited at upper bronchi but more than 90% of
      fibers of the same length and 1 microm in diameter pass through the region.

PMID- 11341545
TI  - Asbestos tissue burden study on human malignant mesothelioma.
AB  - Asbestos fibers in the lung and mesothelial tissues (mesotheliomatous tissue and
      hyaline plaque) taken from 151 human malignant mesothelioma cases were identified
      and characterized by high resolution analytical electron microscopy. Asbestos
      fibers were present in almost all of the lung tissue as well as in the
      mesothelial tissue. The most common asbestos types seen in the lung were an
      admixture of chrysotile with amphiboles followed by amphiboles alone and
      chrysotile alone. The majority of asbestos types seen in the mesothelial tissues
      were chrysotile alone, followed by chrysotile plus amphibole and amphibole alone.
      A disproportion of asbestos types between the lung and mesothelial tissues was
      frequently observed. The most common pattern of the disproportion was chrysotile
      plus amphibole(s) in the lung and chrysotile only in the mesothelial tissues,
      followed by amphibole(s) in the lung and chrysotile only in the mesothelial
      tissues. Such a disproportion was considered to have been caused by chrysotile
      fiber's strong capacity to translocate from the lung to mesothelial tissues. The
      number of asbestos fibers in the lung was 456.4 x 10(6) fibers/dry gram in
      maximum, 0.08 x 106 fibers/dry gram in minimum and 105 x 10(6) fibers/dry gram on
      average; in the mesothelial tissues it was 240.0 x 106 fibers/dry gram in
      maximum, 0.03 x 106 fibers/dry gram in minimum and 49.84 x 106 fibers/dry gram on
      average. These numbers were greater than those seen in the general population.
      The majority of asbestos fibers detected in the lung and mesothelial tissues were
      shorter than 5 microm in length. Asbestos fibers fit to Stanton's hypothetical
      dimensions (> or =8.0 microm in length and < or =0.25 microm in diameter) were
      only 4.0%, since the majority of these fibers were shorter (<8 microm) and
      thinner (<0.25 microm) fibers. We concluded that such short, thin asbestos fibers
      should not be excluded from those contributing to the induction of human
      malignant mesothelioma. The present study supports that chrysotile asbestos can
      induce human malignant mesothelioma, since, in some of the mesothelioma cases,
      asbestos fibers detected in both the lung and mesothelial tissues, or lung tissue
      alone or mesothelial tissues alone were exclusively chrysotile fibers.

PMID- 11341546
TI  - Asbestos exposure in malignant mesothelioma of the pleura: a survey of 557 cases.
AB  - A series of 557 malignant mesotheliomas of the pleura diagnosed in the Trieste
      Monfalcone area, Italy, in the period 1968-2000 were reviewed. The series
      included 492 men and 65 women, aged between 32 and 93 years (median age 69
      years). Necropsy findings were available in 456 cases (82%). Occupational
      histories were obtained from the patients themselves or from their relatives by
      personal or telephone interviews. Routine lung sections were examined for
      asbestos bodies in 442 cases. In 109 cases isolation and counting of asbestos
      bodies were performed. A majority of people had histories of working in the
      shipyards. Asbestos bodies were observed in lung sections in 67% of the cases.
      Lung asbestos body burdens after isolation ranged between 20 bodies and about 10
      millions of bodies/g dried tissue. Latency periods (time intervals between first
      exposure to asbestos and death) ranged between 14 and 75 years (mean 48.8 years,
      median 51.0). Latency periods among insulators and dock workers were shorter than
      among the other categories. High asbestos consumption occurred in many countries
      in the 1960s and in the 1970s. The data on latency periods obtained in the
      present study suggest that a world mesothelioma epidemic has to be expected in
      the coming decades.

PMID- 11341547
TI  - A trial on the quantitative risk assessment of man-made mineral fibers by the rat
      intraperitoneal administration assay using the JFM standard fibrous samples.
AB  - We tried to evaluate the carcinogenic risk of man-made mineral fiber based on the
      mesothelioma incidence in female F344 rats after intraperitoneal administration.
      Rats (female F344/ Nslc, 5-week-old, n=330) were observed for 2 years after the
      intraperitoneal administration of 5 to 20 mg of 9 types of the JFM (Japan Fibrous
      Material Research Association) standard fiber samples (glass wool, rock wool,
      micro fiber glass, three types of refractory fiber, potassium titanate whisker,
      silicon carbide whisker, titanium oxide whisker), wollastonite (natural fiber)
      and UICC chrysotile B. All rats administered 10 mg of silicon carbide whisker had
      developed peritoneal mesothelioma within a year. The cumulative incidence of
      peritoneal mesothelioma at the end of the experiment was 85% for 10 mg UICC
      chrysotile B, 77% for 10 mg of potassium titanate whisker, 70% for 5 mg of
      silicon carbide whisker, 20% for 5 mg of potassium titanate whisker, 20% for 20
      mg of refractory fiber 2 and 10% for 20 mg of refractory fiber 1. Carcinogenicity
      was estimated 2.4 times for silicon carbide whisker and 0.23 for potassium
      titanate whisker in comparison with UICC chrysotile B. It has been well
      documented from several experimental studies that man-made fibers are safer than
      asbestos because of the different durability in the lung. Present results
      consistently suggest that man-made fibers with high durability have similar or
      higher risk as carcinogen than asbestos.

PMID- 11341548
TI  - Short term effect of silicon carbide whisker to the rat lung.
AB  - We studied the short-term effect of silicon carbide whisker (SiCW) in vivo by
      instillation and inhalation to the rat lung. SiCW was instilled low dose (2
      mg/0.5 ml saline) or high dose (10 mg/ 0.5 ml) intratracheally into the lungs of
      25 rats. SiCW was also inhaled to another 25 rats at the average concentration of
      10.4 mg/m3 for 1 month. In instillation study, the lung had focal alveolitis with
      the destruction of alveolar wall especially at 3 days after the instillation, and
      the lesion remained as an aggregated foci of SiCW at 6 months. The 'inflammation
      score' of the instilled group by point counting method of the specimen
      correspondingly decreased gradually. In inhalation group, a minimum inflammatory
      change was observed. Collagen deposition in the aggregated foci of SiCW with
      accumulated alveolar macrophages and neutrophils was not progressive during the
      observed period. These findings suggest that SiCW may cause a minor effect to the
      rat lung in 6 months after exposure.

PMID- 11341549
TI  - Pathology of human malignant mesothelioma--preliminary analysis of 1,517
      mesothelioma cases.
AB  - The author reviewed 1,517 human malignant mesothelioma cases from 1975 through
      August 2000. These mesothelioma cases were definite or probable in diagnostic
      certainty. Sources of these cases varied including asbestos insulation workers,
      UNARCO workers, Cancer and Leukemia B mesothelioma panel cases and random cases.
      Pathology materials consisted of autopsy, biopsy and rare cytology specimens.
      92.3% of these patients were male, and 85.8% were between 50 and 79 years in age.
      The major primary site of the tumor was the pleura (73.1%). However, in a group
      of the asbestos insulation workers, the peritoneum was the more common primary
      site of malignant mesothelioma, compared to the pleura. Histologically,
      epithelial cell type was the majority (61.1%), followed by biphasic (22.1%) and
      fibrosarcomatous (16.4%). A double primary tumor (malignant mesothelioma
      associated with other cancer) was present in 32 of the 1,517 cases. These 32
      cancers included lung cancers, renal cell carcinomas, colorectal cancers,
      pancreatic cancers and a cancer of the larynx, which are known to be at higher
      risk among asbestos insulation workers. The latency period of the vast majority
      (98.1%) of these mesothelioma cases were longer than 20 years. It is well
      accepted that cigarette smoking does not contribute to the induction of malignant
      mesothelioma. Indeed, the present study confirmed that 19.9% of these
      mesothelioma patients had never smoked cigarettes.

PMID- 11341551
TI  - A patient with asbestos-induced lung cancer complicated by silicosis.
AB  - A 76-year-old male died of lung cancer. At first, he was diagnosed as a
      silicosis, because he had worked for 30 years as a caster in shipyard and large
      opacities detected by chest x-ray and CT scanning. After the operation of lung
      cancer, numerous asbestos bodies were observed in the operated lung tissues. The
      detailed occupational inquiry revealed his asbestos use as a caster in shipyard.
      Early stage of asbestosis was suspected by chest CT scanning, but not definitely
      diagnosed in premortal examinations. Asbestosis, pleural plaques, silicosis and
      large cell carcinoma of the lung were histopathologically confirmed at the
      autopsy. A patient with asbestos-induced lung cancer complicated by silicosis was
      rarely published in the literature.

PMID- 11341550
TI  - Urinary 8-oxo-7, 8-dihydro-2'-deoxyguanosine and biopyrrins levels among
      construction workers with asbestos exposure history.
AB  - It has been suggested that oxidative stress is associated with the cancers caused
      by asbestos. Since construction workers are sometimes exposed to low levels of
      asbestos, we investigated whether oxidative stress was elevated in construction
      workers who had been exposed to low levels of asbestos. The subjects were 48
      Japanese construction workers. The defined asbestos-exposed group consisted of
      subjects who had the history of suspected exposure to asbestos and were diagnosed
      to have irregular opacities or pleural plaques. We measured the amount of 8-oxo
      7, 8-dihydro-2'-deoxyguanosine (8-oxodG) and biopyyrins in the urine of the
      subjects. The results showed that 8-oxodG and biopyyrins levels in the defined
      asbestos-exposed group were higher, although they were not statistically
      significant, than those in the control group. In addition, the urinary 8-oxodG
      levels tended to correlate positively with the duration of suspected exposure to
      asbestos. These results suggest that even low-level asbestos exposure may induce
      oxidative stress and that the resulting's the oxidative stress might be related
      to lung cancer in construction workers.

PMID- 11341552
TI  - An operated case of lung cancer with pleural plaques: its asbestos bodies, fiber
      analysis and asbestos exposure.
AB  - This case was a 79-year-old man with pleural plaques, which had been pointed out
      in the left lung field on chest X-ray six years ago. A new shadow in the right
      chest appeared in 1999 and was closely examined. Cytological class IV carcinoma
      was detected in his lung tissue obtained by broncho-fiberscope. Lobectomy of the
      right upper lobe was performed, and calcified pleural plaques were found on the
      chest wall. The clinical diagnosis was poorly differentiated squamous cell
      carcinoma, T1N0M0. In World War II when he was 26 years old, he had worked as a
      boiler man on a battle cruiser for one year. The amount of asbestos bodies (AB)
      was 3,348 per gram dry lung tissue. The cores of AB and asbestos fibers were
      examined and showed that amosite was the most prevalent and crocidolite,
      tremolite and chrysotile were present in that order. After leaving the navy, he
      had worked as a farmer throughout his life, suggesting that he had never
      contacted asbestos occupationally after being a boiler man. It is strongly
      suggested that he had been exposed to asbestos during his work as a boiler man
      and that produced pleural plaques and lung cancer 50 years' later.

PMID- 11341553
TI  - Sympathetic predominance in young male white-collar workers with mild to moderate
      hypertension.
AB  - In order to investigate the difference in diurnal variation of autonomic control
      between young male mild to moderate hypertensive and normotensive white-collar
      workers, we accessed heart rate variability with ambulatory blood pressure for
      over 24 hours including work and sleep periods. Both mean systolic and diastolic
      blood pressures (SBP and DBP) were significantly (p<0.01) higher in hypertensives
      (HT, n=11) than normotensives (NT, n=11) in all phases, whereas heart rate was
      not different between them in any phase. Blood pressures during work period (on
      duty) were significantly higher than those during non-work period (off-duty) in
      both NT and HT. High frequency (HF; 0.15-0.40 Hz) power showed a circadian
      pattern in phase with the sleep-wake cycle. Both HF and low frequency (LF; 0.05
      0.15 Hz) powers in HT were significantly lower than that in NT during the sleep
      period (p<0.05). LF/HF ratio showed a circadian pattern that was almost opposite
      of the pattern in HF power. Twenty-four-hour average LF/HF in HT was higher than
      that in NT (p<0.05). Especially during on-duty, LF/HF in HT was significantly
      higher than in NT (p<0.05). The increase of SBP and LF/HF from off-duty period to
      on-duty period (deltaSBP and deltaLF/HF) showed significant positive correlation
      (r=0.67, P<0.05) in HT group, suggesting that the SBP elevation during on-duty in
      HT may be coupled with sympathetic activation. These results suggest that HT
      showed significantly reduced parasympathetic control during sleep and an
      increased sympathetic activity especially during on-duty as compared with NT. Our
      findings imply that persistence of sympathodominant states together with reduced
      vagal activity in young mild to moderate hypertensive workers may be related to
      future cardiovascular disorders.

PMID- 11341554
TI  - Effect of benzene, toluene, xylene on the semen quality and the function of
      accessory gonad of exposed workers.
AB  - The effects on semen and the function of accessory gonad of workers after short
      and long term exposure to benzene, toluene, and xylene were examined. The semen
      and blood of 24 married workers exposed to benzene, toluene, and xylene were
      collected. Routine sperm characteristic, acrosin activity, and Lactate
      dehydrogenase C4 (LDH-C4) relative activity were detected. The results showed
      that benzene, toluene, and xylene were found in the blood and semen of some ex
      workers at workplaces where the air concentration of benzene, toluene, and xylene
      exceeded the maximum allowable concentration (MAC). No such solvents were
      detected in the blood and semen of workers of the control group. The sperm
      vitality and sperm motility decreased in the exposed workers. The mean acrosin
      activity, gamma-GT activity and LDH-C4 relative activity in the exposed workers
      were lower, and fructose concentration was higher than those in the control.
      There were negative correlations between sperm vitality, sperm activity, acrosin
      activity, or LDH-C4 relative activity and working history. These results suggest
      that the mixture of these solvents could affect the sperm and the function of
      accessory gonad. This might be one reason of the abnormal pregnancy outcome among
      the wives of workers exposed to benzene, toluene, and xylene.

PMID- 11341555
TI  - Fifteen year follow-up study of VC and FEV1 in dust-exposed workers.
AB  - A baseline survey of 3457 male workers exposed to various forms of dust from 11
      medical facilities throughout Japan was carried out in 1978 or 1979. We completed
      the present follow-up study 15 years later on 693 of the men. Vital capacity (VC)
      and forced expiratory volume in one second (FEV1) were analyzed as indices of
      lung function. We examined factors that affected both baseline and interval
      changes in VC and FEV1 by stepwise multiple regression analysis. In the cross
      sectional data analysis of baseline, height, profusion rate (PR) and age were
      selected as predictor variables for VC and FEV1, additionally duration of working
      for FEV1. It indicated that baseline VC decreased by 84.0 ml with each increase
      in PR classification. Similarly, baseline FEV1 decreased by 146.6 ml with
      increasing PR. Baseline VC and FEV1 were both positively influenced by subject
      height. In the longitudinal analysis, baseline PR, age and smoking habits were
      selected for predictor variables for decline of VC and FEV1. It indicated a
      negative influence of baseline PR classification on VC and FEV1 changes (-5.0 and
      -7.5 ml/y, respectively). Smoking decreased VC and FEV1 by 6.1 and 5.8 ml/y,
      respectively.

PMID- 11341556
TI  - Lower percentage of CD56+ cells associated with long working hours.
AB  - In a study of 142 Japanese men from a cross-section of the workforce of a
      technology development company, we found that the percentage of CD56+ cells was
      inversely correlated with the number of hours worked per week. A low CD56+ cell
      percentage was associated with longer weekly working hours and shorter daily
      sleeping hours.

PMID- 11341557
TI  - Measurement of airborne fibers: a review.
AB  - Current fiber measurement techniques arose primarily due to health concerns over
      asbestos exposure. Fiber toxicity appears to be primarily a function of fiber
      concentration, dimensions and durability in the lungs. There are two basic
      approaches to fiber measurement. Fibers can be collected on filters and counted
      or analyzed by light or electron microscopy; alternatively, fibers can be
      detected directly using a combination of fiber alignment and light scattering
      techniques. All of these measurement approaches work best when the fibers are
      simple rod-shaped particles. However, most fibers can exist as curved rods,
      complex bundles of fibrils, and agglomerates of fibers and compact particles.
      These non-ideal shapes contribute to measurement bias and variability.

PMID- 11341558
TI  - Retrospective view of airborne dust levels in workplace of a chrysotile mine in
      Ural, Russia.
AB  - The Bazhenovskoye chrysotile asbestos deposit has been exploited for 115 years.
      All the technological operations in the quarry are accompanied by the formation
      of high-dispersion asbestos-containing aerosols. The dust concentrations at the
      miner's working places for the last 30 years (1970-2000) were at or below the
      Russian MACs(m.s.) level (4.0 mg/m3). The seasonal precipitation amount in the
      deposit area causes a rise in dust content in certain periods. The maximum
      density of asbestos respirable fibres exceeded 2.7 f/cm3. All the identified
      fibres belonged to chrysotile asbestos, and no amphibole asbestos, such as
      tremolite asbestos, has been identified. An excessive dust level remains, despite
      the dust content level decrease, at the work sites of oversized lump drillers and
      unloaders, and oncopathology heightened risk remains in these occupational
      groups, as a result.

PMID- 11341559
TI  - The carcinogenicity of chrysotile asbestos--a review.
AB  - The world production of asbestos has been declining dramatically in recent years,
      particularly in Europe and the United States. However, increases have occurred in
      Asian nations and chrysotile is the dominant fiber used. Important uses are in
      cement products, wallboards, friction products and textiles. From studies in the
      United States and Great Britain, chrysotile has been shown to increase the risk
      of lung cancer and to produce mesothelioma in exposed workers.

PMID- 11341560
TI  - Asbestos-related lung cancer and mesothelioma in Japan.
AB  - In Japan, crocidolite had been used for asbestos cement pipe and spraying, and
      amosite had been used for building board and spraying. These two types of
      asbestos had stopped to use in Japan in the late 1970s. An extreme increase in
      imported asbestos (all 3 commercial types) was observed between 1960 and 1974. In
      1960, 77,000 tons of asbestos were imported, and reached the peak as 352,316 tons
      in 1974. This extreme rise of asbestos imports corresponds with the recent rapid
      increase in mortality of malignant pleural mesothelioma. Between 1995 and 1999,
      an estimated mean annual death from pleural mesothelioma was about 500. The
      annual number of compensated occupational respiratory cancers due to asbestos
      exposure has also been increasing. Up to the end of March 2000, 162 cases with
      malignant mesothelioma and 197 cases with lung cancer were compensated. As for
      lung cancer, epidemiological studies are scanty in Japan. Limited environmental
      data of the working places in asbestos textile factories suggests that heavy
      asbestos exposure in the past made deaths from respiratory diseases. Less
      asbestos exposure will enable exposed workers to survive enough to reach cancer
      age. Even now smoking rate among males in Japan are over 50%. So lung cancer
      deaths caused by the interaction between smoking and asbestos exposure will be
      continuing.

PMID- 11341561
TI  - Epidemiology of occupational asbestos-related diseases in China.
AB  - In 1950s and 60s, asbestosis had been a major health hazard for asbestos exposed
      workers. In the late 1970s, lung cancers with or without asbestosis were found
      among asbestos workers. All cohort studies on asbestos workers and on chrysotile
      miners in China showed excess deaths from lung cancer. In a large scale of cohort
      study on asbestos workers, a synergistic effect was found between cigarette
      smoking and asbestos exposure in the production of lung cancer. There have been
      not so many cases of malignant mesotheliomas reported, so far. In the cohort of
      chrysotile miners, 4 cases of pleural mesothelioma were observed. In the large
      scale of cohort study on asbestos workers in 9 factories using only chrysotile
      only one case of pleural mesothelioma was detected for 10 years' observation. In
      another 2 cohort studies, 2 cases of peritoneal mesotheliomas were found, one in
      Shanghai asbestos factory where a small amount of crocidolite had been used in
      1960s, and one in Anqing asbestos factory that was located near tremolite mine.
      Further study is needed especially for the relationship between exposure to
      Chinese chrysotile and malignant mesotheliomas.

PMID- 11341562
TI  - Biological effects of asbestos fibers on human cells in vitro--especially on
      lymphocytes and neutrophils.
AB  - Biological effects of asbestos fibers were reviewed in relation to the polyclonal
      activation of human lymphocytes and to the release of free radicals from human
      neutrophils in vitro. Chrysotile, crocidolite, and amosite asbestos activate CD4+
      T lymphocytes polyclonally, followed by activation-induced cell death (a type of
      apoptosis). The activation is HLA class II dependent, and certain Vbeta
      repertoire, e.g. Vbeta 5.3, are detected among the fractionated T cells with a
      high Ca++ level that had been stimulated by asbestos fibers. These observations
      support the possibility that asbestos acts as a superantigen, and that asbestos
      stimulate lymphocytes repeatedly in vivo. It has been reported that asbestos
      induced cytotoxicity can be suppressed by the scavengers of superoxide or
      hydroxyl radical. Some of these scavengers such as dimethylsulfoxide (DMSO) or
      retinoic acid are known as inducers of cell differentiation. The biological
      functions of DMSO for cell differentiation of HL-60 cells to neutrophils are
      suppressed by co-culturing of crocidolite asbestos, because DMSO reacts with the
      hydroxyl radical released after the stimulation with crocidolite and spent
      itself. Superoxide dismutase (SOD) inhibited the effects of crocidolite, reacting
      rapidly with *O2- before the secondary release of *OH. It seems to be probable
      that asbestos fibers, especially crocidolite, suppress the tissue cell
      differentiation by releasing free radicals and by wasting inducers of cell
      differentiation as radical scavengers.

PMID- 11341563
TI  - In vitro studies on biological effects of fibrous minerals.
AB  - Asbestos substitutes have been used recently in industrial various applications.
      Since certain asbestos substitutes have similar characteristics of asbestos, they
      require urgent in vitro and in vivo evaluation of these asbestos substitutes
      prior to occupational applications. Though in vitro studies do not offer precise
      assessment of toxicity of the fibers, it is possible to provide useful
      information as to the biological effects of asbestos and its substitutes. This
      review articles described the findings of in vitro experiments in investigation
      of biological effects of asbestos and man made mineral fibers (MMMF) and their
      correlation with in vivo assays; 1. Cytotoxicity, geometry and dimension of
      fibers. 2. In vitro biological effects of fibers on a mass basis and a numerical
      basis. 3. Mechanism of cytotoxicity, carcinogenecity and cell proliferation
      including in vitro cytokines production. The relationships between the in vitro
      and the in vivo biological effects of fibers do not always coincide. Therefore,
      safety of the fibers must be assessed in both in vivo and in vitro using an inert
      fiber as negative control. Additionally, evaluation of safety of these fibers in
      vitro must be conducted in comparable concentrations, sizes and numbers of fibers
      for used in in vivo experiments.

PMID- 11341564
TI  - New theorems on global convergence of some dynamical systems.
AB  - In this paper, we discuss dynamical behaviors of recurrently asymmetrically
      connected neural networks. We propose a new approach to study global convergence
      of the networks. Better test conditions for global convergence are given.

PMID- 11341565
TI  - Bayesian approach for neural networks--review and case studies.
AB  - We give a short review on the Bayesian approach for neural network learning and
      demonstrate the advantages of the approach in three real applications. We discuss
      the Bayesian approach with emphasis on the role of prior knowledge in Bayesian
      models and in classical error minimization approaches. The generalization
      capability of a statistical model, classical or Bayesian, is ultimately based on
      the prior assumptions. The Bayesian approach permits propagation of uncertainty
      in quantities which are unknown to other assumptions in the model, which may be
      more generally valid or easier to guess in the problem. The case problem studied
      in this paper include a regression, a classification, and an inverse problem. In
      the most thoroughly analyzed regression problem, the best models were those with
      less restrictive priors. This emphasizes the major advantage of the Bayesian
      approach, that we are not forced to guess attributes that are unknown, such as
      the number of degrees of freedom in the model, non-linearity of the model with
      respect to each input variable, or the exact form for the distribution of the
      model residuals.

PMID- 11341566
TI  - Temporal clustering with spiking neurons and dynamic synapses: towards
      technological applications.
AB  - We apply spiking neurons with dynamic synapses to detect temporal patterns in a
      multi-dimensional signal. We use a network of integrate-and-fire neurons, fully
      connected via dynamic synapses, each of which is given by a biologically
      plausible dynamical model based on the exact pre- and post-synaptic spike timing.
      Dependent on their adaptable configuration (learning) the synapses automatically
      implement specific delays. Hence, each output neuron with its set of incoming
      synapses works as a detector for a specific temporal pattern. The whole network
      functions as a temporal clustering mechanism with one output per input cluster.
      The classification capability is demonstrated by illustrative examples including
      patterns from Poisson processes and the analysis of speech data.

PMID- 11341567
TI  - An evaluation of standard retrieval algorithms and a binary neural approach.
AB  - In this paper we evaluate a selection of data retrieval algorithms for storage
      efficiency, retrieval speed and partial matching capabilities using a large
      Information Retrieval dataset. We evaluate standard data structures, for example
      inverted file lists and hash tables, but also a novel binary neural network that
      incorporates: single-epoch training, superimposed coding and associative matching
      in a binary matrix data structure. We identify the strengths and weaknesses of
      the approaches. From our evaluation, the novel neural network approach is
      superior with respect to training speed and partial match retrieval time. From
      the results, we make recommendations for the appropriate usage of the novel
      neural approach.

PMID- 11341568
TI  - Pseudo-outer product based fuzzy neural network fingerprint verification system.
AB  - Fingerprint identification has been used in law enforcement applications over the
      last century, and has become the de facto international standard for positive
      identification. With the emergence of automated fingerprint identification
      technologies, it has assisted in making the once labour-intensive process of
      classifying, searching and matching a thing of the past. As a biometrics proof of
      identification, not many have ventured into the world of fingerprint
      identification using fuzzy neural networks. In this paper, a database of
      fingerprint images is constructed and a fuzzy neural network called the pseudo
      outer product fuzzy neural network (POPFNN) [Zhou, R.W. & Quek, C. (1996). A
      pseudo outer-product based fuzzy neural network. Neural Networks, 9(9), 1569
      1581] is trained to detect similarity between two fingerprints and decide whether
      they belong to the same person. The fundamental idea is that, given a person's
      fingerprints taken under different conditions, the POPFNN based fingerprint
      verification system should be sufficiently robust to distinguish the difference.
      The people providing the fingerprint samples are subjected to different 'adverse'
      conditions; from wetness to chemical treatments. Fingerprint images are taken
      after conditions such as: after a shower, holding pineapples (mild acid from
      fruit), after washing one's hands, etc. The characteristics of POPFNN, such as
      the learning, generalisation, and high computational abilities, make fingerprint
      verification particularly powerful when verifying authentic fingerprints
      subjected to external conditions and recognising spurious ones. In order to
      demonstrate the efficacy of POPFNN and its application in the fingerprint
      verification system (FVS), several types of experiments have been designed and
      implemented in this work. The experimental results and analysis are presented at
      the end of the paper for discussion.

PMID- 11341569
TI  - A what-and-where fusion neural network for recognition and tracking of multiple
      radar emitters.
AB  - A neural network recognition and tracking system is proposed for classification
      of radar pulses in autonomous Electronic Support Measure systems. Radar type
      information is considered with position-specific information from active emitters
      in a scene. Type-specific parameters of the input pulse stream are fed to a
      neural network classifier trained on samples of data collected in the field.
      Meanwhile, a clustering algorithm is used to separate pulses from different
      emitters according to position-specific parameters of the input pulse stream.
      Classifier responses corresponding to different emitters are separated into
      tracks, or trajectories, one per active emitter, allowing for more accurate
      identification of radar types based on multiple views of emitter data along each
      emitter trajectory. Such a What-and-Where fusion strategy is motivated by a
      similar subdivision of labor in the brain. The fuzzy ARTMAP neural network is
      used to classify streams of pulses according to radar type using their functional
      parameters. Simulation results obtained with a radar pulse data set indicate that
      fuzzy ARTMAP compares favorably to several other approaches when performance is
      measured in terms of accuracy and computational complexity. Incorporation into
      fuzzy ARTMAP of negative match tracking (from ARTMAP-IC) facilitated convergence
      during training with this data set. Other modifications improved classification
      of data that include missing input pattern components and missing training
      classes. Fuzzy ARTMAP was combined with a bank of Kalman filters to group pulses
      transmitted from different emitters based on their position-specific parameters,
      and with a module to accumulate evidence from fuzzy ARTMAP responses
      corresponding to the track defined for each emitter. Simulation results
      demonstrate that the system provides a high level of performance on complex,
      incomplete and overlapping radar data.

PMID- 11341570
TI  - Graph matching vs mutual information maximization for object detection.
AB  - Labeled Graph Matching (LGM) has been shown successful in numerous object vision
      tasks. This method is the basis for arguably the best face recognition system in
      the world. We present an algorithm for visual pattern recognition that is an
      extension of LGM ('LGM+'). We compare the performance of LGM and LGM+ algorithms
      with a state of the art statistical method based on Mutual Information
      Maximization (MIM). We present an adaptation of the MIM method for multi
      dimensional Gabor wavelet features. The three pattern recognition methods were
      evaluated on an object detection task, using a set of stimuli on which none of
      the methods had been tested previously. The results indicate that while the
      performance of the MIM method operating upon Gabor wavelets is superior to the
      same method operating on pixels and to LGM, it is surpassed by LGM+. LGM+ offers
      a significant improvement in performance over LGM without losing LGM' s virtues
      of simplicity, biological plausibility, and a computational cost that is 2-3
      orders of magnitude lower than that of the MIM algorithm.

PMID- 11341571
TI  - Neural networks for improved target differentiation and localization with sonar.
AB  - This study investigates the processing of sonar signals using neural networks for
      robust differentiation of commonly encountered features in indoor robot
      environments. Differentiation of such features is of interest for intelligent
      systems in a variety of applications. Different representations of amplitude and
      time-of-flight measurement patterns acquired from a real sonar system are
      processed. In most cases, best results are obtained with the low-frequency
      component of the discrete wavelet transform of these patterns. Modular and non
      modular neural network structures trained with the back-propagation and
      generating-shrinking algorithms are used to incorporate learning in the
      identification of parameter relations for target primitives. Networks trained
      with the generating-shrinking algorithm demonstrate better generalization and
      interpolation capability and faster convergence rate. Neural networks can
      differentiate more targets employing only a single sensor node, with a higher
      correct differentiation percentage (99%) than achieved with previously reported
      methods (61-90%) employing multiple sensor nodes. A sensor node is a pair of
      transducers with fixed separation, that can rotate and scan the target to collect
      data. Had the number of sensing nodes been reduced in the other methods, their
      performance would have been even worse. The success of the neural network
      approach shows that the sonar signals do contain sufficient information to
      differentiate all target types, but the previously reported methods are unable to
      resolve this identifying information. This work can find application in areas
      where recognition of patterns hidden in sonar signals is required. Some examples
      are system control based on acoustic signal detection and identification, map
      building, navigation, obstacle avoidance, and target-tracking applications for
      mobile robots and other intelligent systems.

PMID- 11341572
TI  - Escape hatches for the clonal offspring of serpulid polychaetes.
AB  - Serpulid polychaetes in the genera Filograna and Salmacina reproduce asexually by
      releasing a single bud at a time from their posterior ends into their calcareous
      tubes. Here I show that buds of Salmacina amphidentata gain access to the
      exterior of these tubes via escape hatches built into the tubes by the parent
      worms. Each escape hatch consists of a hole in the tube blocked by a calcareous
      disc that is supported in place by an organic membrane. After buds detach from
      their parents, the calcareous discs are dislodged, and buds begin to form their
      own tubes from the resulting openings. Repeated bouts of asexual reproduction
      result in the formation of aggregations of branched tubes. A survey of Filograna
      and Salmacina spp. from the Atlantic, Indian, and Pacific oceans suggests that
      the formation of escape hatches for clonal offspring is common to many members of
      these genera.

PMID- 11341573
TI  - Factors controlling the expansion behavior of favia favus (Cnidaria:
      Scleractinia): effects of light, flow, and planktonic prey.
AB  - Colonies of the massive stony coral Faviafavus were exposed to different flow
      speeds and levels of light, and to the addition of zooplankton prey. The relative
      importance of each factor in controlling polyp expansion behavior was tested. The
      coral polyps fully expanded when they were exposed to low light intensity (0-40
      micromol m(-2) s(-1)) and high flow speed (15 cm s(-1)), regardless of prey
      presence. They also partially expanded under low and medium light (40-80 micromol
      m(-2) s(-1)) at medium flow speed (10 cm s(-1)). The corals expanded their polyps
      only when they were exposed to light levels below compensation irradiance (Icom:
      light level at which photosynthesis = respiration), which was determined to be
      about 107 +/- 24 micromol m(-2) s. The results presented here indicate that high
      flow, low light, and the presence of planktonic prey induce coral expansion.
      There is a hierarchy of response to these stimuli, in which light level and flow
      speed are dominant over prey presence. Coral response to these three factors is
      probably due to the relative importance of gas exchange and zooplankton prey.

PMID- 11341574
TI  - Development of host- and symbiont-specific monoclonal antibodies and confirmation
      of the origin of the symbiosome membrane in a cnidarian-dinoflagellate symbiosis.
AB  - The "symbiosome membrane" as defined by Roth et al. (1988) is a single, host
      derived membrane that surrounds an endosymbiotic organism, separating it from the
      cytoplasm of the host cell. However, in the case of cnidarian-dinoflagellate
      endosymbioses, clear identification of the symbiosome membrane is complicated by
      the fact that each algal symbiont is surrounded by multiple layers of apparent
      membrane. The origin and molecular nature of these membranes has been the subject
      of considerable debate in the literature. Here we report the development of host
      specific (G12) and symbiont-specific (PC3) monoclonal antibodies that allow
      separation of the host and symbiont components of these multiple membranes. Using
      immunocytochemistry at both the light and the electron microscopic level, we
      present data supporting the conclusion that the definitive symbiosome membrane is
      a single, host-derived membrane, whereas the remainder of the underlying apparent
      membranes surrounding the algal cell are symbiont-derived. The potential for
      macromolecules associated with these membranes to act as cellular signals
      critical to recruiting symbionts and maintaining established symbioses is
      discussed.

PMID- 11341575
TI  - Invertebrate sensory information processing: implications for biologically
      inspired autonomous systems. Proceedings of a workshop. 15-17 June 2000, Woods
      Hole, Massachusetts, USA.

PMID- 11341576
TI  - Fan organs of crayfish enhance chemical information flow.
AB  - Animals as well as autonomous robots need to acquire environmental signals in
      order to adjust their activity in time and space. Some information is accessible
      to the sensors only as a result of specific behaviors for stimulus acquisition.
      Due to the slow rate of molecular diffusion, dispersal of chemical stimuli
      depends on fluid flow. Aquatic crustaceans can generate directed water currents
      by specialized appendages. Here I describe the crayfish fan organs, which are
      feathered flagella of the mouthparts, and their activity in sending and receiving
      chemical signals in environments with stagnant flow conditions. During the power
      stroke, the fan opens and displaces water; during the return stroke, it collapses
      and thereby minimizes drag. These organs can create a variety of flow fields
      including water jets, and in many different directions. Bilateral upward fanning
      draws water horizontally from all directions toward the anterior chemoreceptors.
      Unilateral upward fanning draws water from only one side towards the body. The
      versatility of the crayfish fan organ makes it a candidate for biomimetic
      reconstruction and use in autonomous robots that can search chemical sources.

PMID- 11341577
TI  - Statocysts in crabs: short-term control of locomotion and long-term monitoring of
      hydrostatic pressure.
AB  - Crabs show well-coordinated locomotion. They have proprioceptors similar to those
      of lobsters, but they differ in terms of their balancing systems and their
      condensed nervous system, which allows rapid interganglionic conduction.
      Typically they exhibit dynamically stable locomotion with a highly developed
      semicircular canal system that codes angular acceleration in each of three
      orthogonal planes (horizontal and vertical at 45 degrees and 135 degrees to the
      pitching plane). Left and right interneurons each code one direction of angular
      acceleration, carrying information between the brain and the thoracic ganglia.
      Cell A codes head-up vertical plane angular accelerations. Cell B codes rotations
      in the horizontal plane. Interneurons C and D code headdown vertical plane
      information, carrying it ipsilaterally and contralaterally respectively. These
      interneurons have a central role in locomotion. They are activated and have their
      responsiveness to angular acceleration enhanced before and during locomotion.
      Such simple activation pathways point to how an angular-acceleration-controlled
      robot (CRABOT) could be constructed. Hydrostatic pressure information carried by
      the thread hairs, which also sense angular acceleration, is filtered out from
      direct pathways onto the interneurons, but spectral analysis shows that it still
      has an influence via central pathways. Long-term recordings from equilibrium
      interneurons in free-walking crabs taken from the wild into constant conditions
      show tidally changing frequencies

PMID- 11341578
TI  - Invertebrate-Inspired sensory-motor systems and autonomous, olfactory-guided
      exploration.
AB  - The localization of resources in a natural environment is a multifaceted problem
      faced by both invertebrate animals and autonomous robots. At a first
      approximation, locomotion through natural environments must be guided by reliable
      sensory information. But natural environments can be unpredictable, so from time
      to time, information from any one sensory modality is likely to become
      temporarily unreliable. Fortunately, compensating mechanisms ensure that such
      signals are replaced or disambiguated by information from more reliable
      modalities. For invertebrates and robots to rely primarily on chemical senses has
      advantages and pitfalls, and these are discussed. The role of turbulence, which
      makes tracking a single odor to its source a complex problem, is contrasted with
      the high-fidelity identification of stimulus quality by the invertebrate
      chemoreceptor and by artificial sensors.

PMID- 11341579
TI  - Limulus vision in the marine environment.
AB  - Horseshoe crabs use vision to find mates. They can reliably detect objects
      resembling potential mates under a variety of lighting conditions. To understand
      how they achieve this remarkable performance, we constructed a cell based
      realistic model of the lateral eye to compute the ensembles of optic nerve
      activity ("neural images") it transmits to the brain. The neural images reveal a
      robust encocding of mate-like objects that move underwater during the day. The
      neural images are much less clear at night, even though the eyes undergo large
      circadian increases of sensitivity that nearly compensate for the millionfold
      decreasein underwater lighting after sundown. At night the neurral images are
      noisy, dominated by bursts of nerve impulses from random photon events that occur
      at low nighttime levels of illumination. Deciphering the eye's input to the brain
      begins at the first synaptic level with lowpass temporal and spatial filtering.
      Both neural filtering mechanisms improve the signal-to-noise properties of the
      eye's input, yielding clearer neural images of potential mates, especiallyat
      night. Insights about visual processing by the relatively simple visual system of
      Limulus may aid in the designof robotic sensors for the marine environment.

PMID- 11341581
TI  - View from the boundary.
AB  - Re-implementing biological mechanisms on robots not only has technological
      application but can provide a unique perspective on the nature of sensory
      processing in animals. To make a robot work, we need to understand the function
      as part of an embodied, behaving system. I argue that this perspective suggests
      that the terms "representation" and "information processing" can be misleading
      when we seek to understand how neurobiological mechanisms carry out perceptual
      processes. This argument is presented here with reference to a robot model of
      cricket behavior, which has demonstrated competence comparable to that of the
      insect, but utilizes surprisingly simple central processing. Instead it depends
      on sensory interfaces that are well matched to the task, and on the link between
      environment, action, and perception.

PMID- 11341580
TI  - Parallel processing and image analysis in the eyes of mantis shrimps.
AB  - The compound eyes of mantis shrimps, a group of tropical marine crustaceans,
      incorporate principles of serial and parallel processing of visual information
      that may be applicable to artificial imaging systems. Their eyes include numerous
      specializations for analysis of the spectral and polarizational properties of
      light, and include more photoreceptor classes for analysis of ultraviolet light,
      color, and polarization than occur in any other known visual system. This is
      possible because receptors in different regions of the eye are anatomically
      diverse and incorporate unusual structural features, such as spectral filters,
      not seen in other compound eyes. Unlike eyes of most other animals, eyes of
      mantis shrimps must move to acquire some types of visual information and to
      integrate color and polarization with spatial vision. Information leaving the
      retina appears to be processed into numerous parallel data streams leading into
      the central nervous system, greatly reducing the analytical requirements at
      higher levels. Many of these unusual features of mantis shrimp vision may inspire
      new sensor designs for machine vision.

PMID- 11341582
TI  - Innovative biomechanics for directional hearing in small flies.
AB  - In humans and animals alike, the localization of sound constitutes a fundamental
      processing task of the auditory system. Directional hearing relies on acoustic
      cues such as the interaural amplitude and time differences and also, sometimes,
      the signal spectral composition. In small animals, such as insects, the auditory
      receptors are forcibly set close together, a design constraint imposing very
      short interaural distances. Due to the physics of sound propagation, the close
      proximity of the sound receivers results in vanishingly small amplitude and time
      cues. Yet, because of their directionality, small auditory systems embed original
      and innovative solutions that can be of inspirational value to some acute
      problems of technological miniaturization. Such ears are found in a parasitoid
      fly that acoustically locates its singing cricket host. Anatomically rather
      unconventional, the fly's auditory system is endowed with a directional
      sensitivity that is based on the mechanical coupling between its two hemilateral
      tympanal membranes. The functional principle permitting this directionality may
      be of particular relevance for technological applications necessitating sensors
      that are low cost, low weight, and low energy. Based on silicon-etching
      technology, early prototypes of sub-millimeter acoustic sensors provide evidence
      for directional mechanical responses. Further developments hold the promise of
      applications in hearing aid technology, vibration sensors, and miniature video
      acoustic surveillance systems.

PMID- 11341583
TI  - A biologically inspired controller for hexapod walking: simple solutions by
      exploiting physical properties.
AB  - The locomotor system of slowly walking insects is well suited for coping with
      highly irregular terrain and therefore might represent a paragon for an
      artificial six-legged walking machine. Our investigations of the stick insect
      Carausius morosus indicate that these animals gain their adaptivity and
      flexibility mainly from the extremely decentralized organization of the control
      system that generates the leg movements. Neither the movement of a single leg nor
      the coordination of all six legs (i.e., the gait) appears to be centrally pre
      programmed. Thus, instead of using a single, central controller with global
      knowledge, each leg appears to possess its own controller with only procedural
      knowledge for the generation of the leg's movement. This is possible because
      exploiting the physical properties avoids the need for complete information on
      the geometry of the system that would be a prerequisite for explicitly solving
      the problems. Hence, production of the gait is an emergent property of the whole
      system, in which each of the six single-leg controllers obeys a few simple and
      local rules in processing state-dependent information about its neighbors.

PMID- 11341584
TI  - Insights for robotic design from studies of the control of abdominal position in
      crayfish.
AB  - Studies of the control of position and movement of the abdomen of crayfish
      illustrate a number of features of invertebrate sensory-motor systems that have
      implications for their use to inform robotic design. We use the abdominal slow
      extensor motor system to illustrate three of them here: first, the way in which a
      behaviorally flexible length-servo device can be achieved with very few elements;
      second, the importance of knowledge of the biological and behavioral context in
      which the elements operate; third, that design solutions resulting from natural
      selection have been constrained by the previous evolutionary history of the
      animal, which can affect the outcomes in ways that may not be immediately
      apparent in a design context.

PMID- 11341585
TI  - Increasing sensor flexibility through neuromodulation.
AB  - Both biological and man-made motor control networks require input from sensors to
      allow for modification of the motor program. Real sensory neurons are more
      flexible than typical robotic sensors because they are dynamic rather than
      static. The membrane properties of neurons and hence their excitability can be
      modified by the presence of neuromodulatory substances. In the case of a sensory
      neuron, this can change, in a functionally significant way, the code used to
      describe a stimulus. For instance, extension of the neuron's dynamic range or
      modification of its filtering characteristics can result. This flexibility has an
      apparent cost. The code used may be situation-dependent and hence difficult to
      interpret. To address this issue and to understand how neuromodulation is used
      effectively in a motor control network, I am studying the GPR2 stretch receptor
      in the crustacean stomatogastric nervous system. Several different
      neuromodulatory substances can modify its encoding properties. Comparisons of
      physiological and anatomical evidence suggest that neuromodulation can be
      effected both by GPR2 itself and by other neurons in the network. These results
      suggest that the analog of neuromodulation might be useful for improving sensor
      performance in an artificial motor control system.

PMID- 11341586
TI  - Why do animals have so many receptors? The role of multiple chemosensors in
      animal perception.
AB  - Many animals have an abundance and diverse assortment of peripheral sensors, both
      across and within sensory modalities. Multiple sensors offer many functional
      advantages to an animal's ability to perceive and respond to environmental
      signals. Advantages include extending the ability to detect and determine the
      spatial distribution of stimuli, improving the range and accuracy of
      discrimination among stimuli of different types and intensities, increasing
      behavioral sensitivity to stimuli, ensuring continued sensory capabilities when
      the probability of damage or other loss of function to some sensors is high,
      maintaining sensory function over the entire sensory surface during development
      and growth, and increasing the richness of behavioral output to sensory
      stimulation. In this paper, we use the crustacean chemosensory system as the
      primary example to discuss these functions of multiple sensors. These principles
      may be applicable to the function of autonomous robots and should be considered
      in their design.

PMID- 11341587
TI  - Landing strategies in honeybees, and possible applications to autonomous airborne
      vehicles.
AB  - Insects, being perhaps more reliant on image motion cues than mammals or higher
      vertebrates, are proving to be an excellent organism in which to investigate how
      information on optic flow is exploited to guide locomotion and navigation. This
      paper describes one example, illustrating how bees perform grazing landings on a
      flat surface. A smooth landing is achieved by a surprisingly simple and elegant
      strategy: image velocity is held constant as the surface is approached, thus
      automatically ensuring that flight speed is close to zero at touchdown. No
      explicit knowledge of flight speed or height above the ground is necessary. The
      feasibility of this landing strategy is tested by implementation in a robotic
      gantry, and its applicability to autonomous airborne vehicles is discussed.

PMID- 11341588
TI  - Plume-tracking robots: a new application of chemical sensors.
AB  - Many animals have the ability to search for odor sources by tracking their
      plumes. Some of the key features of this search behavior have been successfully
      transferred to robot platforms, although the capabilities of animals are still
      beyond the current level of sensor technologies. The examples described in this
      paper are (1) incorporating into a wheeled robot the upwind surges and casting
      used by moths in tracking pheromone plumes, (2) extracting useful information
      from the response patterns of a chemical sensor array patterned after the
      spatially distributed chemoreceptors of some animals, and (3) mimicking the
      fanning behavior of silkworm moths to enhance the reception of chemical signals
      by drawing molecules from one direction. The achievements so far and current
      efforts are reviewed to illustrate the steps to be taken toward future
      development of this technology.

PMID- 11341589
TI  - Sensing scenes with silicon.
AB  - Scene analysis, the process of converting sensory information from peripheral
      receptors into a representation of objects in the external world, is central to
      our human experience of perception. Through our efforts to design systems for
      object recognition and for robot navigation, we have come to appreciate that a
      number of common themes apply across the sensory modalities of vision, audition,
      and olfaction; and many apply across species ranging from invertebrates to
      mammals. These themes include the need for adaptation in the periphery and trade
      offs between selectivity for frequency or molecular structure with resolution in
      time or space. In addition, neural mechanisms involving coincidence detection are
      found in many different subsystems that appear to implement cross-correlation or
      autocorrelation computations.

PMID- 11341590
TI  - Sensory architectures for biologically inspired autonomous robotics.
AB  - Engineers have a lot to gain from studying biology. The study of biological
      neural systems alone provides numerous examples of computational systems that are
      far more complex than any man-made system and perform real-time sensory and motor
      tasks in a manner that humbles the most advanced artificial systems. Despite the
      evolutionary genesis of these systems and the vast apparent differences between
      species, there are common design strategies employed by biological systems that
      span taxa, and engineers would do well to emulate these strategies. However,
      biologically-inspired computational architectures, which are continuous-time and
      parallel in nature, do not map well onto conventional processors, which are
      discrete-time and serial in operation. Rather, an implementation technology that
      is capable of directly realizing the layered parallel structure and nonlinear
      elements employed by neurobiology is required for power- and space-efficient
      implementation. Custom neuromorphic hardware meets these criteria and yields low
      power dedicated sensory systems that are small, light, and ideal for autonomous
      robot applications. As examples of how this technology is applied, this article
      describes both a low-level neuromorphic hardware emulation of an elementary
      visual motion detector, and a large-scale, system-level spatial motion
      integration system.

PMID- 11341591
TI  - Hybrids of two closely related tropical sea urchins (genus Echinometra): evidence
      against postzygotic isolating mechanisms.
AB  - A series of cross-fertilization experiments were conducted with two unnamed,
      sympatric species of sea urchins in the Echinometra mathaei species complex,
      Echinometra sp. A (Ea) and Echinometra sp. C (Ec). Heterogametic fertilization
      success was high when eggs of Ec and sperm of Ea were involved, and low with eggs
      of Ea and sperm of Ec. Hybrids produced from crosses in either direction
      developed normally to sexually mature adults; Ea x Ea were largest in test size,
      followed by Ec (ova) x Ea (sperm), Ea (ova) x Ec (sperm), and Ec x Ec,
      respectively. Color patterns of the hybrids were closer to the maternal
      coloration, whereas other characters such as relative test dimensions and spine
      lengths, morphology of tubefoot and gonad spicules, and gamete sizes were
      intermediate. Fertilization rates in F1 backcrosses were high, minimizing the
      possibility that hybrid infertility is a postzygotic mechanism of reproductive
      isolation. On the other hand, intensive surveys failed to find individuals with
      hybrid characteristics in the field, suggesting that natural hybridization
      between the two species is rare. Prezygotic isolating mechanisms, such as
      microhabitat separation and gamete incompatibility, at least between Ea eggs and
      Ec sperm, most likely maintain the genetic integrity of these two closely related
      species.

PMID- 11341592
TI  - Autologous blood transfusion as an immunomodulator in experimental sepsis.
AB  - BACKGROUND: Homologous blood transfusion is associated with immunosuppressive
      consequences. Some clinical and experimental studies have suggested an
      immunostimulating action of autologous blood transfusion. The aim of this paper
      is to ascertain the effects of either homologous blood transfusion or autologous
      blood transfusion on the lymphocyte subsets and cytokines in a model of intra
      abdominal sepsis. MATERIALS AND METHODS: There were three study groups. Group A:
      10 Wistar-Furth (WF) rats underwent cecal ligation and puncture (CLP) aimed at
      causing an intra-abdomial sepsis; Group B: 10 WF rats underwent CLP plus 1 ml
      homologous blood perioperative transfusion obtained from Fisher-344 rat while
      Group C: 10 WF rats underwent CLP plus 1 ml autologous blood perioperative
      transfusion. Changes of peripheral lymphocyte subsets, percentages of total T
      lymphocytes (CD3), Helper T-lymphocytes (CD4), supressor/cytotoxic T-lymphocytes
      (CD8), CD4/CD8 ratio, Interleukin-2 receptor expression (IL-2R) and cytokines IL
      1 and TNF-alpha were measured in peripheral blood on the preoperative, 1st, 3rd
      and 7th postsepsis (PO) days. RESULTS: Rats in homologous transfused group showed
      a decrease of %CD4 on the 3rd PO (from preoperative to 3rd PO;p < 0.01; and from
      1st to 3rd PO; p < 0.05) and on the 7th PO (from preoperative to 7th PO; p <
      0.05); %CD8 increased from preoperative to 3rd PO (p < 0.05), from 1st to 3rd PO
      (p < 0.01) and from 1st to 7th PO (p < 0.05). An initial decrease on day 1 (p <
      0.01) followed by an increase on the 3rd PO (p < 0.01) with regard to IL-2R and a
      significant increase of IL-1 levels within the first 24h (p < 0.01). Rats in
      autologous transfused group showed an increase of %CD3 from preoperative to 7th
      PO (p < 0.05), and from 3rd to 7th PO (p < 0.01). CONCLUSIONS: We observed that
      homologous blood transfusions induce a greater alteration in the cellular immune
      response and of the cascade of cytokines than autologous transfusions. This
      modulates the variations of the immune response induced by sepsis.

PMID- 11341593
TI  - Esophageal and gastric motile response to rectal distension with identification
      of a recto-esophagogastric reflex.
AB  - PURPOSE: To investigate the effect of rectal distension with a balloon simulating
      fecal mass, on the motile activity of the esophagus and stomach. METHOD: Nine
      healthy volunteers (7 men, 2 women, mean age 46.6 +/- 4.7 years) were studied. A
      manometric tube was introduced into the stomach and a balloon-tipped catheter
      into the rectum. The gastric and esophageal pressure response to rectal
      distension in increments of 10 ml up to 80 ml of water was recorded. The test was
      repeated after rectal anesthetization. RESULTS: There was no esophageal or
      gastric pressure response to rectal distension up to 70 ml. At 80 ml distension,
      the rectal pressure rose (p < 0.001) and the balloon was dispelled to the
      exterior. Meanwhile, the pressure in the esophagus, corpus of the stomach and
      pyloric antrum showed a significant drop (p < 0.05) and in the lower esophageal
      sphincter and pyloric sphincter a significant rise (p < 0.05). There was no
      esophageal or gastric response to distension of the anesthetized rectum.
      CONCLUSION: Lower esophageal and pyloric sphincter contraction and esophageal and
      gastric relaxation during rectal distension appear to delay gastric emptying. The
      response of the esophagus and stomach to rectal distension seems to be elicited
      by a reflex which we call "recto-esophagogastric reflex". It is suggested that
      rectal lesions or dysfunction might disturb the esophageal or gastric motility
      and vice versa. The reflex may therefore prove to be of significance in the
      diagnosis of such disorders.

PMID- 11341594
TI  - The effect of intraislet somatostatin immunoneutralization on insulin secretion
      in the isolated perfused rat pancreas.
AB  - BACKGROUND: There is evidence of a local inhibitory effect of somatostatin on
      insulin secretion in the isolated human pancreas, but this has not been shown in
      a rat model. The possible phasic effect of somatostatin on insulin secretion has
      not been demonstrated. AIMS: This study was undertaken to determine if
      somatostatin has a local regulatory effect on phasic insulin secretion within a
      rat pancreas model. METHODS: The basal and glucose stimulated secretion of
      insulin was compared with and without immunoneutralization of somatostatin using
      a somatostatin antibody in an isolated perfused rat pancreas model. High
      concentration, high affinity monoclonal somatostatin antibody was perfused
      through isolated rat pancreata. Radioimmunoassay for insulin was performed on the
      portal effluent. RESULTS: Immunoneutralization of somatostatin during basal
      insulin secretion produced a rise in insulin secretion of 551 +/- 163% that
      approached significance. Immunoneutralization during glucose stimulated insulin
      secretion produced a significant rise in insulin secretion compared to the
      control group of 2,678 +/- 187% vs. 535 +/- 39% (p < 0.05). The phase I vs. the
      phase II response in the glucose stimulated pancreas was similar in the presence
      of control antibody, 867 +/- 351% vs. 900 +/- 398% (p = NS). With somatostatin
      immunoneutralization, the glucose stimulated pancreas had a significantly higher
      phase II response than phase I; 3,832 +/- 688% vs. 2,516 +/- 431% (p < 0.05).
      CONCLUSION: These data indicate that intraislet somatostatin is an inhibitor of
      insulin secretion in the isolated perfused rat pancreas. This effect occurs
      primarily in phase II of insulin secretion.

PMID- 11341595
TI  - Prognostic factors in node-negative squamous cell carcinoma of the thoracic
      esophagus.
AB  - BACKGROUND: Among several clinicopathological factors influencing the outcome of
      patients with esophageal carcinoma, the presence or absence of lymph node
      metastasis is the most important. Prognostic indicators, however, in patients
      without lymph node involvement have not been fully understood. MATERIALS AND
      METHODS: Out of 247 patients with primary squamous cell carcinoma of the thoracic
      esophagus between February 1981 and December 1998, 154 patients (62.3%) underwent
      esophagectomy with curative intent; 78 patients (50.6%) had no lymph node
      metastasis. Clinicopathological characteristics of those node-negative 78
      patients were investigated. RESULTS: Pathological tumor stages (pT) were pT1 in
      44 patients, pT2 in 24 patients, pT3 in 9 patients, and pT4 in one patient. Forty
      six patients are alive free of cancer and another one with pT2N0 tumor is alive
      with recurrence. Four patients died of recurrence; one in pT1 and three in pT3.
      The remaining 27 patients died of miscellaneous causes other than esophageal
      cancer. The 1-, 3-, 5-, and 10-year overall survival rates of all 78 patients
      including in-hospital mortality were 86.3%, 73%, 66.5%, and 34.6%, respectively.
      The 3- and 5-year survival rates were 75.4% and 67.7% for those with pT1, T2
      tumor (n = 68) and 57.1% and 57.1% for those with pT3, T4 tumor (n = 10) (p =
      0.0151). The factors influencing overall survival rate were patient age (< 65 vs.
      > or = 65), depth of invasion (pT1,T2 vs. pT3, T4), time of operation (< or = 420
      min vs. > 420 min), and estimated blood loss (< or = 810 ml vs. > 810 ml). More
      elderly patients died of unrelated causes to esophageal cancer than younger
      patients. Among those four variables, the patient age (p = 0.0114) and depth of
      invasion (p = 0.0443) were independent prognosticators for survival determined by
      multivariate analysis. CONCLUSION: For follow-up of elderly patients with node
      negative esophageal cancer, evaluation of medical problems is more important than
      detection of recurrence. pT2N0 stage tumors should be considered a group with an
      excellent prognosis like pT1N0 tumors.

PMID- 11341596
TI  - Novel methods to evaluate controlled reperfusion techniques in cardiac surgery.
AB  - BACKGROUND: This manuscript describes two novel techniques that may be useful for
      comparing methods to reperfuse the heart during cardiac operations. These
      techniques are based on measurements of intra-myocyte ion content and the
      analysis of reperfusion arrhythmias. METHODS: Myocyte ion content was measured in
      normal porcine hearts before and after ischemia (cardioplegic arrest, CP arrest)
      using atomic absorption spectroscopy. A cobalt-EDTA complex served as the extra
      cellular marker. Cobalt-EDTA was infused into the aorta together with blood or
      cardioplegia (CP) solution. Myocardial biopsies were taken prior to CP arrest and
      upon successful defibrillation 5 min after initiating reperfusion. Ventricular
      fibrillation (VF) was recorded prior to ischemia, and then during reperfusion. VF
      wavefront (WF) morphology and propagation patterns were analyzed using computer
      algorithms. Electrophysiologic variables for measuring VF included the
      multiplicity index (a descriptor of VF organization), the number of WFs detected
      (nwaves/s) and the mean peak first derivative of electrogram voltage with respect
      to time (mp d V/dt). RESULTS: Intra-cellular sodium content increased, while
      intra-cellular magnesium content decreased between control and reperfusion
      measurements (p < 0.05). Electrophysiologic recovery was characterized by
      increasingly rapid depolarization (i.e. more negative mp d V/dt) and an
      increasing nwaves/s during the first minute of post-CP reperfusion. CONCLUSIONS:
      Atomic absorption spectroscopy and computer-based analysis of reperfusion VF
      successfully measured metabolic and electrophysiologic events that occurred
      during controlled reperfusion. These methods may be useful for comparing
      controlled reperfusion techniques.

PMID- 11341597
TI  - Female urethral reconstruction with amnion grafts.
AB  - BACKGROUND: About 1-5% of female babies are born with Mullerian duct
      abnormalities such as Mayer-Rokitansky-Kuster-Hauser syndrome, urogenital sinus,
      and cloacal malformation. In some intersex cases the urethra and vagina both
      empty into a urogenital sinus. One major issue in single-stage surgical
      reconstruction of large urethral defects is tissue availability. AIM: To
      investigate the usefulness of amnion grafts in female urethral reconstruction.
      METHODS: This is a prospective cohort study describing the use of amnion grafts
      for urethral reconstruction in 8 patients with ambiguous genitalia associated
      with low or mid-portion urethrovaginal confluence or vaginal agenesis with low
      external urethral meatus implantation. RESULTS: The procedure was felt to be
      easy, quick and effective for appropriate restoration of both the function and
      the cosmetics of the lower urogenital tract. CONCLUSIONS: Amnion grafts add a
      valuable option to the surgical armamentarium and offers potential advantages for
      urogenital reconstructive surgery.

PMID- 11341598
TI  - Liposome mediated gene transfer into GH3 cells, and rat brain, liver and gut:
      comparison of different polar or aliphatic domains.
AB  - BACKGROUND: Cationic liposomes may be used in gene transfer. However, different
      liposome configurations have varying efficiency in different tissues. AIMS: To
      compare multiple lipids during gene transfer into the intestinal mucosa, liver
      and central nervous system in the adult rat. We evaluate different lipid
      aliphatic and polar head domains. MATERIALS AND METHODS: Nine cationic or neutral
      phospholipids, combined with a cationic cholesterol derivative, have been
      compared to Lipofectin. Transfection was into GH3 cells and the adult rat brain,
      liver or intestinal mucosa. Results Optimum DNA:lipid ratio was lowest (1:2) in
      the intestinal mucosa and highest in GH3 cells (1:40). Lipofectin ", was most
      effective in brain and GH3 cells but had no activity in intestinal mucosa.
      Saturated cationic lipids transfect differently in GH3 cells and GI mucosa than
      in liver and brain. However, with saturated neutral phospholipids, GH3 cells,
      intestinal mucosa and liver transfect similarly. DOTAP the longest unsaturated
      cationic lipid (18:1) was most effective in the intestine, whereas DMEPC the
      shortest saturated neutral lipid (14:0) was optimal in the liver. CONCLUSIONS: In
      this study we propose a rational approach, based on systematic variations of
      lipids, to optimize liposome mediated gene transfer into the ventricular system
      of the brain, the liver and gastro-intestinal tract in the adult rat.
      Additionally, we demonstrate the feasibility of gene transfer into the mucosal
      cells of the gastro-intestinal tract as well as throughout the ventricular system
      of the rat brain. This requires liposomes which contain a cationic cholesterol
      derivative.

PMID- 11341599
TI  - Research on the best chemohyperthermia technique of treatment of peritoneal
      carcinomatosis after complete resection.
AB  - BACKGROUND: The complete or almost complete resection of peritoneal
      carcinomatosis (PC) followed by intraperitoneal chemohyperthermia (IPCH) is
      potentially capable of curing some patients presenting with disease confined to
      the peritoneum. AIMS: The aim of this prospective phase I-II study was to develop
      an efficient IPCH procedure with good thermal homogeneity and good spatial
      diffusion, that would be reproducible (and thus could be standardized and
      exported), and to evaluate patient tolerance and its efficiency in eradicating
      tumor tissue. METHODS: Seven IPCH procedures were tested successively in 32
      patients (up to a total of 35 IPCH). Each procedure was tested in at least 4
      patients before modifications for technical reasons or due to inacceptable
      tolerance. Five of them were followed by early postoperative intraperitoneal
      chemotherapy (EPIC) lasting 4 days. Thermal homogeneity was measured with 6
      thermal probes placed in different positions inside the abdominal cavity. Spatial
      diffusion was studied in the last patients by adding methylene blue to the IPCH
      liquid. The mean follow-up was 23.85 months for the series. RESULTS: From the
      technological point of view, we have progressively shown that procedures with
      closure of the abdomen are not satisfactory: it was impossible to obtain thermal
      homogeneity when the entire parietal wound was closed, but markedly improved when
      only the skin was closed. However, these "closed" procedures did not allow us to
      treat all surfaces at risk. The peritoneal cavity "expander" did not permit
      treatment of the parietal wound and an indeterminate amount of the perfusion
      oozed out at its periphery. The open technique with traction of the skin upwards
      was superior. Using different procedures successively undermined the quality of
      the postoperative results. Three patients (8.6%) died and morbidity (albeit
      minimal) occurred in 27 patients (77%) during the postoperative course. Mortality
      and morbidity were significantly correlated (P = 0.02) with the peritoneal index
      (scoring the extent of PC). The 2-year survival rate was 60% and PC did not recur
      in 49% of the patients. The survival rate was correlated with the extent of PC
      (peritoneal index greater than or below 15) (P = 0.004), and with the absence of
      extraperitoneal disease (P = 0.01).

PMID- 11341600
TI  - Ultrathin cutting needle biopsy histology in the tissue diagnosis of acute
      pancreatitis--experimental study and application in a human case.
AB  - BACKGROUND AND AIMS: This study was to assess whether the tissue obtained with an
      ultrathin cutting needle, that is as thin as used for aspiration cytology and
      bacteriology, can give enough material to diagnose acute pancreatitis in rat
      model and in a human case. METHODS: Wistar rats were randomly allocated into
      control group (n = 6), cerulein group (n = 6), ligation group (n = 6) and bile
      salt group (n = 6). In the cerulein, ligation and bile salt groups acute
      pancreatitis was induced by cerulein intraperitoneal injections, low ligation of
      common biliopancreatic duct and sodium taurodeoxycholate intraductal injection,
      respectively. Serum amylase activity was measured and a large cut specimen and
      two ultrathin needle biopsy specimens were obtained from the pancreas for light
      microscopic histology. Oedema, acinar cell necrosis, haemorrhage or fat necrosis,
      and leukocyte infiltration were evaluated semiquantitatively and compared with
      large cut specimens. RESULTS: The pancreatitis groups revealed different severity
      in oedema, acinar cell necrosis, haemorrhage or fat necrosis, and leukocyte
      infiltration. The needle biopsy showed 100% sensitivity and 100% specificity in
      the diagnosis of acute pancreatitis. The histopathologic scores showed a good and
      significant correlation between ultrathin biopsy and large cut specimens in all
      the four histologic parameters, especially in oedema and acinar cell necrosis. A
      human case is presented, whose percutaneous ultrathin needle biopsy histology was
      successfully applied for diagnosing acute pancreatitis. CONCLUSIONS: The
      ultrathin needle biopsy histology can give enough material for the diagnosis of
      acute pancreatitis. Further studies with ultrasonography guided percutanous or
      endosonography guided transduodenal technique will be needed to assess the role
      of tissue sampling in acute pancreatitis.

PMID- 11341601
TI  - Experience with a generic quality of life instrument in a general surgical
      practice.
AB  - BACKGROUND: The new emphasis on measuring outcomes has generated interest in
      quality of life instruments. One such instrument is the SF-36, a well-tested and
      widely used health status survey. This survey was prospectively evaluated over a
      three month period in a general surgical practice. STUDY DESIGN: Ninety-seven
      patients completed 115 surveys. Patients were asked the following questions: (1)
      Do you like the survery? (2) Does it accurately reflect your present health
      condition? (3) Does it reflect the reason for which you came to the surgeon?
      Patients were then categorized into distinct groups. The results were averaged
      and compared with national norms of a cross-sectional survey of 2,474
      individuals, 79.5% of whom had medical problems. RESULTS Sixty-four percent of
      patients liked the survey; 77% thought it accurately reflected their health
      status; but only 45% thought it accurately reflected the problem for which they
      came to the surgeon. Patients with breast masses did not differ from the norms in
      any of the eight domains measured by the SF-36. Those with fibrocystic
      disease/mastalgia showed poorer scores in three domains; patients with thyroid
      disease had poorer scores in three domains; those with irritable bowel
      syndrome/chronic abdominal pain had poorer scores in six domains; and those with
      anorectal disease in three domains. Follow-up surveys were obtained in 18
      patients. The measurement of the effects of treatment by the SF-36 was variable.
      CONCLUSION: In conclusion, the SF-36 can measure changes in health status as
      caused by disease seen by a general surgeon; however, it may be too insensitive
      to measure the effects of surgery on improvement in health status.

PMID- 11341602
TI  - Expression of molecular messages for angiogenesis by fibroblasts from aneurysmal
      abdominal aorta versus dermal fibroblasts.
AB  - BACKGROUND: The molecular messages which drive angiogenesis in the adventitia of
      an aneurysmal aorta are uncertain. The emergence of molecular phenotyping by cDNA
      expression arrays provides a simple and rapid method for a preliminary approach
      to the analysis of molecular messengers for neovascularization in cultured cells.
      In the present experiment, fibroblasts cultured from the aorta of a patient with
      abdominal aortic aneurysm (AAA) were compared with normal dermal fibroblasts, on
      an array that evaluates several mRNAs with known roles in angiogenesis. METHODS:
      RNA was isolated from fibroblasts and purified. Labelled cDNA probes were
      generated from a mixture of RNA and CDS primers. Atlas Array membranes (Clontech)
      were prehybridized by ExpressHyb buffer. The cDNA probes were then added to the
      membranes, which were exposed to Phospholmage Screen (Molecular Dynamics) and
      analysed by a dedicated computer program. RESULTS: The most significantly
      upregulated mRNAs in AAA (by comparison to dermal fibroblasts) were: MCAF, MDNCF,
      EGR-1, VEGF, FGF-7, Mal protein, Mac Marcks, Transducin, Interleukin-9 receptor,
      and TNF. CONCLUSION: VEGF and TNF were upregulated, as expected. However, the
      upregulation of monocyte chemotactic and activating factor (MCAF) and monocyte
      derived neutrophil chemotactic factor (MDNCF) suggest that the fibroblast may be
      more significantly involved in driving the inflammatory response that leads to
      AAA than previously realized.

PMID- 11341603
TI  - Enhanced cytokine response to surgical trauma in patients with colorectal cancer.
AB  - OBJECTIVE: Cancer is an immunologic challenge, and it was hypothesized that the
      presence of a cancer could modulate the cytokine response to operative trauma.
      SETTING: University hospital, Sweden. SUBJECTS: Patients operated with colonic or
      rectal resections; 9 patients with colorectal cancer and 16 patients with benign
      lesions--8 of which were inflammatory. INTERVENTION: Venous blood samples were
      collected preoperatively; every 30 min intraoperatively; 6 h postoperatively and
      daily for 6 days in the postoperative period. MAIN OUTCOME MEASURES: IL-1beta and
      TNF-alpha were analyzed by commercial ELISAs, whereas IL-6 was analyzed by the B9
      bio-assay. RESULTS: Preoperative cytokine levels were similar in the malignant
      and benign groups, but intraoperative IL-6, IL-1beta and TNF-alpha serum levels
      and postoperative IL-6 and TNF-alpha serum levels were significantly (p < 0.05)
      higher in the malignant group. CONCLUSION: The results indicate that colorectal
      malignancy enhances the IL-1beta, TNF-alpha and IL-6 response to surgical trauma.

PMID- 11341604
TI  - Extrapancreatic multiorgan injury in a severe sublethal acute pancreatitis model.
AB  - In order to develop a new severe but sublethal acute pancreatitis model for the
      study of clinically relevant extrapancreatic multiorgan injury, we have induced
      acute pancreatitis in a rat model by intraductal injection with low dose and
      moderate concentration of bile acid under low pressure. We examined the
      structural and functional features in the pancreas, lung, liver and kidney. The
      animals were divided into two groups: the bile acid injection group and the
      control group. In the bile acid injection group, acute necrotizing pancreatitis
      was induced by intraductal administration of 0.2 ml of 2.0% bile acid under 30 cm
      H2O pressure, while the controls underwent the sham operation. The two groups
      were divided into six subgroups (8 rats for each) and sacrificed at 12, 24, 36,
      48, 72 and 144 h, respectively. The pancreatitis induced hyperamylasemia,
      ascites, pancreatic oedema, haemorrhage, acinar cell necrosis and extensive fat
      necrosis without early mortality. Accompanied with the pancreatic injury, the
      function and histologic changes have developed continuously in the kidney and
      liver for 72 and 144 h in the bile acid injection animals respectively. No
      pancreatitis associated pulmonary changes were found. Taking into account the
      results with the two previously developed models of pancreatitis, we conclude
      that the extrapancreatic injury in acute pancreatitis is found in the liver,
      kidney and lung, in that order, depending on the severity of pancreatitis. The
      present sublethal pancreatitis model, in comparison with the two previously
      studied acute pancreatitis models, is perfect for pathogenetic and therapeutic
      study of liver and renal changes in acute necrotizing pancreatitis.

PMID- 11341605
TI  - One-year experience with a new expanded polytetrafluoroethylene vascular graft
      for hemodialysis.
AB  - Hemodialysis access achieved through a prosthetic vascular graft has become more
      popular, especially in diabetic and older patients and those who have had several
      unsuccessful surgical accesses. From January to December 1996, we implanted a
      newly available expanded polytetrafluoroethylene (ePTFE) graft (DIASTAT Vascular
      Access Graft) that allows early cannulation in 18 patients (11 men and 7 women;
      mean age +/- SD, 63.7 +/- 11 years). Thirteen of these patients had at least one
      failed vascular access. All grafts were cannulated for dialysis within 7 days of
      implantation, with flow rates > or = 300 ml/min. The time to hemostasis after the
      first cannulation ranged from 2 to 4 min. The primary patency rate at one year
      was 56%. Four grafts developed thrombosis requiring surgical intervention; three
      were salvaged and one was removed. The one-year assisted or cumulative patency
      rate was 72%. One patient had persistent bleeding requiring graft revision
      immediately after surgery. The bleeding stopped and its origin was not
      determined. There were no graft infections or hematomas. Because of the early
      cannulation possible with the DIASTAT graft, as well as the lesser time to
      hemostasis than that generally achieved with standard ePTFE grafts, this
      prosthesis is a good alternative to autogenous access construction.

PMID- 11341606
TI  - Cimetidine does not influence TIL in breast cancer.
AB  - Cimetidine is known to have immunomodulatory effects and this study aimed to
      examine the effect of pre-operative cimetidine treatment on lymphocytic
      infiltration in n = 72 women with breast cancer randomised to 400 mg bd or
      placebo for five days presurgery. A combined index was devised by adding
      infiltrating lymphocyte percentage and lymphoid score. There were no significant
      differences in circumferential infiltrate and lymphoid follicles in cimetidine
      treated patients and control patients with breast cancer.

PMID- 11341607
TI  - Optimal revascularization of segmental pancreatic transplant.
AB  - Vascular anastomotic thrombosis is one of the most frequent complications after
      segmental transplantation of the pancreas (STP). We propose a new type of
      vascular anastomosis to reduce the rate of vascular thrombosis following STP. For
      this purpose we used double arterial-double venous anastomosis (DADVA). Four
      different types of vascular anastomosis used for STP were studied and compared.
      The rate of vascular anastomotic thrombosis was evaluated in correlation with the
      type of vascular anastomosis used. Traditional vascular anastomosis (TVA) was
      complicated by vascular thrombosis in 51.9% of cases. DADVA reduced rate of
      vascular thrombosis to 2.6% (P < 0.01).

PMID- 11341608
TI  - Thromboxane A2 receptor antagonist prevents pancreatic microvascular leakage in
      rats with caerulein-induced acute pancreatitis.
AB  - This study was designed to evaluate the protective effect of thromboxane A2
      (TXA2) receptor antagonist, seratrodast, against pancreatic injuries during acute
      pancreatitis. Acute pancreatitis was induced in rats by intravenous infusion of a
      supramaximal dose of caerulein (5 microg/kg x h for 4 h). In this model, marked
      hyperamylasemia, a significant increase in pancreatic water content, and a
      significant increase in pancreatic micro-vascular leakage of Evans blue dye were
      observed. Pancreatic subcellular redistribution of a lysosomal enzyme, cathepsin
      B from the lysosomal fraction to the zymogen fraction as well as a significant
      increase in pancreatic trypsin content were also observed. Pretreatment with
      seratrodast at a dose of 2 mg/kg (twice, 8 and 4 h before caerulein infusion)
      significantly inhibited these pancreatic injuries including hyperamylasemia,
      increased pancreatic microvascular leakage, redistribution of cathepsin B and
      increased pancreatic trypsin content. These results suggest that TXA2 may be
      involved in the pathogenesis of acute pancreatitis in the early stage of the
      disease and that TXA2 receptor antagonist might be of therapeutic value for
      treatment of acute pancreatitis.

PMID- 11341609
TI  - Experimental studies on small intestinal pouch motility and evacuation.
AB  - The aim of the study was to investigate pouch motility and evacuation under
      standardised conditions with a minimum of external influence. METHODS: Ileal J
      pouches had been constructed 30 cm proximal to the ileocecal valve in 10 dogs (6
      pelvic/4 gastric configuration). After 8 weeks the following examinations were
      performed: (1) measurement of pouch compliance by balloon distension, (2)
      measurement of pouch contractions by strain gauge transducers, (3) radiological
      imaging of pouch contractions and evacuation, (4) evacuation scintigraphy and (5)
      radiological determination of small intestinal transit time. RESULTS: Compliance
      (2.3 +/- 1.1 mmHg/ml) and small intestinal transit time (31.6 +/- 7.5 h) were
      significantly higher in the pouch group than in controls (0.5 +/- 0.2 mmHg/ml,
      8.0 +/- 2.8 h; p < 0.05). Scintigraphy and radiography showed delayed pouch
      evacuation (t(1/2) = 109 +/- 52 min). Strain gauge measurements revealed
      irregular pouch contractions without detectable propagation. Contraction
      amplitudes (40.4 +/- 22.9 g) and frequencies (10.4 +/- 1.0/min) were equal all
      over the pouch. There were no functional differences between gastric and pelvic
      pouch configuration. CONCLUSION: Small intestinal pouches act as reservoirs.
      Uncoordinated motility patterns contribute to this function. Other factors than
      pouch motility are responsible for evacuation.

PMID- 11341610
TI  - Synthesis of type I and III collagen, expression of fibronectin and matrix
      metalloproteinases-1 and -13 in hernial sac of patients with inguinal hernia.
AB  - Since many years the importance of a weakness of the soft tissue for the
      development of hernias is discussed controversially. The tensile strength of the
      tissue is supposed to depend largely on the varying proportion of type I collagen
      with its high tensile strength and the immature type III collagen. Their relation
      is regulated by several collagenases, mainly matrix metalloproteinases-1 and -13
      (MMP-1 and MMP-13), whereas fibronectin plays a key role for the adherence of
      cells within the extracellular matrix. The aim of this study was to investigate
      whether an alteration in type I and type III collagen synthesis, amounts of MMP-1
      and MMP-13 and the expression of fibronectin were associated with the development
      of inguinal hernia. We analysed the hernial sac of patients with indirect (n = 9)
      and direct (n = 7) inguinal hernias and peritoneum in controls (n = 7) by
      immunohistochemistry and Western blot analysis. The results showed that the ratio
      of relative amount of I/III collagen was markedly decreased in patients with
      either indirect or direct hernias as compared with controls (p < 0.001) with a
      concomitant increase in type III collagen synthesis. MMP-13 was expressed neither
      in the hernial sac nor in the peritoneum of the controls, but the positive
      reactions of MMP-1 were found in the surface of the subserosa of the hernial sac
      in patients with indirect or direct hernias without any difference compared to
      controls. Furthermore, the relative amount of fibronectin in patients with either
      indirect or direct hernias is not significantly different from controls (p >
      0.05). In regard to the known alterations of the collagen metabolism in fascia
      and skin of hernia patients the changed collagen I/III ratio with its increase of
      type III collagen in hernial sacs support the presence of a systemic disturbance
      of collagen metabolism. The absence of changes of the expression of collagenases
      (MMP-1, MMP-13) and the constant levels of fibronectin underline the central role
      of collagen synthesis for the development of indirect or direct hernias.

PMID- 11341611
TI  - Endotoxin fails to stimulate inositol triphosphate production in macrophages.
AB  - Inositol Triphosphate (IP3) production is an early cell signaling event which
      leads to mobilization of intracellular calcium (Ca++). We examined whether
      bacterial endotoxin (lipopolysaccharide, LPS) stimulates IP3 production in
      macrophages pretreated with LPS (tolerant) or not. METHODS: RAW 264.7 macrophages
      were cultured at 5 x 10(6) cells in RPMI supplemented with 10% FCS. LPS tolerance
      was induced by pretreating macrophages (Tol) for 19 h with 10 ng/ml of LPS. Non
      tolerant (Non-Tol) macrophages received no LPS pretreatment. Macrophages were
      next washed, repleted with fresh media, and stimulated with 100 ng/ml LPS. Paired
      cultures were stimulated with 1 microM platelet activating factor (PAF), a known
      stimulant of IP3 production. Following 1, 10, and 15-min stimulation intervals,
      IP3 was extracted with trichloroacetic acid and measured by receptor displacement
      assay. RESULTS: LPS did not stimulate IP3 production in either Non-Tol or Tol
      macrophages. In contrast, PAF stimulated significant increases in IP3 levels
      within 1 min in both Non-Tol (9.5 +/- 3.0 pmol/ml) and Tol (9.5 +/- 2.4 pmol/ml)
      macrophages. Non-Tol IP3 levels returned to baseline by 10 min, while Tol IP3
      levels remained significantly elevated (8.2 +/- 1.7 pmol/ml). CONCLUSIONS: Unlike
      PAF, bacterial LPS fails to stimulate IP3 production in macrophages. Furthermore,
      IP3 production could not be elicited in cultured macrophages repetitively
      stimulated with LPS.

PMID- 11341612
TI  - Rejection pattern of simultaneously transplanted cardiac and skeletal muscle
      grafts in a rat model.
AB  - BACKGROUND: We studied the correlation of cardiac and skeletal muscle allograft
      rejection in a rat model to assess the feasibility of using biopsies from
      simultaneously transplanted skeletal muscle for surveillance of cardiac graft
      rejection. METHODS: Thirty Lewis rats (RT1l)) underwent simultaneous heterotopic
      heart and cutaneous maximus flap (HHCM) allotransplant. Seven recipient rats
      (control) received syngeneic HHCM grafts from Lewis donors while the remaining 23
      (study group) received HHCM grafts from Brown Norway (RT1n) donors. Control rats
      were sacrificed after 7 days while rats in the study group were serially
      sacrificed at days 1-7 after transplantation. No immunosuppression was given. The
      tissue sections from the HHCM grafts were assessed for acute rejection based on
      the grading system adopted by the International Society for Heart and Lung
      Transplantation. RESULTS: As expected, all the control rats had no evidence of
      rejection. One study animal developed an infection in the skeletal muscle
      allograft and was excluded. Two study animals had no evidence of rejection when
      sacrificed 1 day after transplant. The remaining 20 rats developed acute cellular
      rejection in their graft(s). Upon comparison of acute cellular rejection between
      the heterotopic heart and the cutaneous maximus flap grafts, rejection correlated
      grade for grade in 75% (15 of 20 rats). All five rats that did not have identical
      grades of rejection had mild rejection (grades IA, IB and II). Presence or
      absence of rejection, therefore, correlated in 20/22 rats: 15/20 rats with
      cardiac rejection and 2/2 rats without cardiac rejection. CONCLUSION: Cardiac and
      skeletal muscle allografts have similar pattern of rejection with little grade to
      grade variability. The clinical implications for surveillance of cardiac
      rejection warrants further investigation.

PMID- 11341613
TI  - Use of laparoscopic techniques in colorectal cancer surgery.

PMID- 11341614
TI  - Are peritoneal seeding and port site tumor recurrences a problem with
      laparoscopic cancer treatment?

PMID- 11341615
TI  - Technique of laparoscopic left hemicolectomy.

PMID- 11341616
TI  - Controversies regarding laparoscopic versus open resections for colorectal
      cancer.

PMID- 11341617
TI  - Laparoscopic therapy of colonic diverticular disease.

PMID- 11341618
TI  - Treatment options for advanced pelvic recurrence of rectal cancer.

PMID- 11341619
TI  - Mesorectal excision (TME) in the operative treatment of rectal cancer.

PMID- 11341620
TI  - Prevention of complications in colorectal surgery.

PMID- 11341621
TI  - Surgeon-related factors and outcome in rectal cancer treatment.

PMID- 11341622
TI  - Preoperative radiotherapy in rectal cancer--is there a survival benefit?

PMID- 11341623
TI  - Critical review and future perspectives of the colon pouch.

PMID- 11341624
TI  - Total anorectal reconstruction after abdominoperineal resection.

PMID- 11341625
TI  - Functional results of total mesorectal excision for rectal cancer.

PMID- 11341626
TI  - Dynamic graciloplasty.

PMID- 11341627
TI  - The anal artificial sphincter in severe anal incontinence.

PMID- 11341628
TI  - Bilateral gluteoplasty.

PMID- 11341629
TI  - Extrapancreatic organ manifestations in a moderately severe acute pancreatitis
      model.
AB  - In order to study the extent of clinically relevant extrapancreatic organ injury
      in a moderately severe pancreatitis model, we examined the structural and
      functional features of the pancreas, lung, liver and kidney in a rat model
      simulating gallstone pancreatitis. The animals were divided into three groups:
      the low-ligation group, the high-ligation group and the control group, and
      sacrificed at 6, 24, 42, 60 and 96 h. In the low-ligation group, moderately
      severe acute pancreatitis was induced by the ligation of the common
      biliopancreatic duct plus intralipid intragastric injection, while controls
      underwent the ligation of the bile duct above the pancreas (the high-ligation
      group) or only sham operation (the control group) with fat injection. The
      pancreatitis induced hyperamylasemia, pancreatic oedema, haemorrhage, acinar cell
      necrosis and extensive fat necrosis. Accompanied with a peak value of serum
      amylase activity 24 h after the induction, the kidney changes developed,
      characterized by decrease in urine output, increase in serum urea and creatinine,
      and proximal convoluted tubular damage under electron microscope. There were no
      pancreatitis associated lung or liver changes. These results suggest that this
      model can be used to study the pathogenesis and therapy of renal injury during
      acute moderately severe pancreatitis.

PMID- 11341630
TI  - The effect of various types of splenectomy on the development of B-16 melanoma in
      mice.
AB  - Two hundred and sixty CB57BL/J6 mice were used in an experimental protocol
      designed to investigate the effects of four different varieties of splenectomy on
      the growth rate of subcutaneously implanted GB-16 melanoma. In addition, the mean
      and absolute survival of the mice, the histopathology of the tumour and the
      effects of the same procedures on the immunological status of the tumour-bearing
      animals as assessed by serum IgG levels and immunoelectrophoresis were
      determined. The effects of timing of splenectomy and the removal of the primary
      tumour after splenectomy on the above parameters were also annotated. The
      following were found: 1. Splenectomy performed 8 days after B-16 melanoma tumour
      implantation in mice i.e. in the early period of oncogenesis, lengthened the
      survival of the grafted experiments, delayed tumour growth, reduced the
      "activity" of the tumour and caused pseudoencapsulation of the tumour by fibrous
      tissue. It increased, but not by a statistically significant degree (p > 0.05),
      the circulating levels of the IgG immunoglobulin. 2. Splenectomy performed 28
      days prior to grafting of the same tumour did not affect the circulating IgG
      levels nor did it prolong survival; however it reduced the rate of tumour growth
      and pseudoencapsulation of the tumour was observed. 3. Splenectomy at the early
      stages of oncogenesis in combination with surgical removal of the primary tumour
      increased absolute and mean survival, delayed the tumour growth rate, increased
      the time to relapse and reduced the "activity" of the pseudoencapsulated tumour.

PMID- 11341631
TI  - A method for the measurement of glucose oxidation using the constant infusion of
      stable isotope.
AB  - We developed a method to measure the oxidation of glucose using the primed
      constant infusion of [U-13C] glucose in critically ill patients fed by total
      parenteral nutrition. The results obtained from the isotopic method were compared
      to those from indirect calorimetry in the critically ill patients. A patient with
      esophageal carcinoma was used for the preliminary study. The study was performed
      on the third postoperative day, assuming severely stressed state. Priming doses
      of NaH13CO3 at a dosage of 0.32 mg/kg and D-[U-13C] glucose at a dosage of 0.32
      mg/kg were injected. D-[U-13C] glucose was then infused at an infusion rate of
      0.004 mg/kg/min. It was revealed that the time required for an isotopic plateau
      was approximately 45 min in plasma glucose and 120 min in an expired air in
      highly stressed state. Isotopic measurement and indirect calorimetry were
      performed simultaneously pre- and postoperatively on three patients who underwent
      surgery for esophageal carcinoma. Increased fat oxidation was obtained by the
      isotopic method, whereas indirect calorimetry indicated nonprotein RQ above 1.0.
      Isotopic measurement offered a useful information that cannot be obtained from
      indirect calorimetry concerning the energy metabolism in the critical illness.
      Thus our method for the measurement of glucose oxidation is both simple and
      useful in investigating the energy metabolism in critically ill patients.

PMID- 11341632
TI  - The stenosis ratio: a new tool for the diagnosis of degenerative spinal stenosis.
AB  - CLINICAL RELEVANCE: Low back pain from lumbar spinal stenosis is a significant
      source of morbidity, especially among the elderly population. Accurate diagnosis
      is imperative for effective treatment to be initiated. This paper presents a
      quantitative method for the evaluation of spinal stenosis that, when used in
      conjunction with CT and MRI, may greatly aid the clinician in the diagnosis of
      this debilitating condition. OBJECTIVE: Precise clinical tools for the diagnosis
      of spinal stenosis are severely lacking. Low back pain and dysfunction derived
      from lumbar spinal stenosis is a significant source of morbidity, especially
      among the elderly. Despite its importance, there has been little progress made
      towards establishing valid, quantitative criteria for the diagnosis of spinal
      stenosis. We present a new quantitative tool for the diagnosis of lumbar
      stenosis, the Stenosis Ratio (SR). METHODS: CT scans and MRI scans of 43 patients
      presenting with clinico-radiographic evidence of lumbar stenosis were used. The
      patient group consisted of 13 males and 30 females between the ages 49 and 82
      with average age of 67. CT and MRI/scans of 43 patients were digitized and
      computer analyzed. Measurements of SR, defined as the ratio of the cross
      sectional dural area of the motion segment to that of the stable segment, were
      established for L3-L4, L4-L5 and L5-S1 stenotic levels and compared to SR values
      for a non-stenotic (internal control) level, L2-L3. RESULTS: The L4-L5 level had
      the lowest SR value of 0.71, followed by 0.74 at L3-L4, and 0.87 at L5-S1. Ninety
      five percent confidence intervals of (0.66, 0.81), (0.62, 0.81), and (0.73, 1.00)
      were found for SR values at levels L3-L4, L4-L5 and L5-S1 respectively. The SR at
      L2-L3 had a mean value of 1.37 with a 95% confidence interval of (0.970, 1.78).
      At all levels, SRs were significantly lower for the spinal stenotic L3-S1 levels
      than for the L2-L3 control as confirmed by a student's t-test (p < 0.05).
      CONCLUSION: In a select population of patients with spinal stenosis confirmed by
      neuroradiological assessment, values of SRs were consistently and significantly
      lower than controls. We believe that measurements of SRs may provide reproducible
      quantitative measures for the diagnosis of spinal stenosis. SR values below the
      95% confidence limit may be indicative of lumbar stenosis. Through the use of
      ratios, inherent differences in patient size are controlled for, thus allowing
      comparison of values between patients and treatment groups and effective clinical
      diagnosis of spinal stenosis.

PMID- 11341633
TI  - Image analysis for quantitation of solid tumor drug sensitivity.
AB  - BACKGROUND: A method of assessing chemosensitivity of tissue has been described
      by Rotman et al. The aim of this study was to use image analysis to provide a
      more rapid and quantitative means of assessing drug effect on tissue
      proliferative capacity. METHOD: Fluoropyrimidine sensitive Ward rat colon
      adenocarcinoma tumor was implanted onto collagen impregnated cellulose fibers
      suspended on metal grids at an air-fluid interface and kept in a 95% air/5% CO2
      incubator at 37 degrees C. The fluorescent microscopic image captured by a
      silicon intensified target (low light detecting) camera and linked to an image
      processing unit was measured for fluorescent brightness and tumor image area.
      Blinded 5-Fluorouracil (5-FU) drug treatment was begun 8 days after tumor
      explantation on the collagen-cellulose matrix. Tumor image area and fluorescent
      brightness were measured at 24 h pretreatment, 48 h posttreatment, and at 48 h
      post drug removal. RESULTS: Nontreated tumor cultures demonstrated an increase in
      area and fluorescent brightness with time following tumor implantation on the
      collagen gel. Dose responsiveness was seen with increasing concentrations of 5
      FU. At the highest clinically achievable concentration of 5-FU (500 microM),
      there was a 39% decrease in area compared with the nontreated group, 113%. Linear
      dose responsiveness was not demonstrated between 50 and 150microM 5-FU.
      CONCLUSIONS: Fluoropyrimidine activity was demonstrated with the implemented
      image analysis system. The in vitro tumor sensitivity to FU using collagen gel
      was consistent with responsiveness of tumors in vivo borne by rats.

PMID- 11341634
TI  - Comparison of functional state between bilateral lung volume reduction surgery
      and pulmonary rehabilitation: a six-month followup study.
AB  - STUDY OBJECTIVE: The effectiveness of bilateral lung volume reduction surgery
      (BLVRS) in the improvement of functional state in severe chronic obstructive
      pulmonary disease (COPD) has not been reported. This study examined the effects
      of BLVRS on subjective and objective measures of functional state (FS) and
      compared these effects with those gained from pulmonary rehabilitation (PR).
      METHODS: Twenty-eight consecutive patients were studied. Of 13 BLVRS and 15 PR
      patients enrolled in the study, 12 and 13 patients, respectively, completed the 6
      month protocol. Pulmonary function (FEV1, FVC, and FEF25-75) was measured by
      spirometry. Subjective FS was measured with the activity component of the
      Pulmonary Functional Status and Dyspnea Questionnaire (PFSDQ) and objective FS
      was determined as the 6-min walk distance (6mwD). Additionally, the maximal
      dyspnea intensity measured with the Borg scale during the 6-min test was
      recorded. All outcomes were recorded prior to, and six months following
      treatment. RESULTS: In patients undergoing BLVRS, FEV1 and FVC increased (17.3%
      and 16.8%) while in those treated with PR alone, FEV1 and FVC decreased (7.6% and
      16.1%,p < 0.05). The subjective functional state (PFSDQ) was also significantly
      different between BLVRS and PR alone (PFSDQ = -49.4% vs. +4.7%, p < 0.05).
      Although the absolute distance walked over 6 min did not reach statistical
      significance, the BLVRS group increased the distance by 20% while the PR alone
      group had a decrease (-28%). Both groups demonstrated a reduction in dyspnea with
      exercise but the volume reduction patients showed a significantly greater
      reduction (PR = -1.0; BLVRS = -2.6, p < 0.05). CONCLUSION: BLVRS results in
      greater improvement in pulmonary function, dyspnea with exercise, and subjective
      FS when compared to PR 6 months after surgery.

PMID- 11341635
TI  - Prevention of abdominal adhesions does not interfere with jejunal anastomosis
      healing.
AB  - OBJECTIVE: To determine the prevention of adhesions interferes with the healing
      of jejunal anastomosis. PARTICIPANTS: Twenty-five rats allocated into five
      groups. INTERVENTIONS: Group 1- intraperitoneal injection of 12ml-1% sodium
      carboxymethylcellulose (SCMC). Groups 2-5- jejunal anastomosis. Groups 3 and 5-
      intraperitoneal SCMC-12 ml. The animals of the groups 2 and 4- only anastomosis.
      The rats of the groups 2 and 3- reopened on the 5th and those of groups 4 and 5
      on the 21st postoperative days. Abdominal adhesions were graded and burst
      pressure of the anastomosis measured. Histological studies of anastomotic healing
      were performed. RESULTS: Group 1 did not present any abnormality. Groups reopened
      on the 5th day did not differ in the burst pressures of the anastomosis and
      adhesion grades. The burst pressures in the groups reopened on the 21st
      postoperative day also did not differ. Histological patterns were similar in both
      groups on the 5th day, but on the 21st day, the rats treated with SCMC showed a
      maturer intestinal healing. CONCLUSIONS: The prevention of adhesions not only did
      not interfere with jejunal anastomotic resistance, but also improved the
      intestinal healing in the rat.

PMID- 11341636
TI  - Perioperative urinary catheterisation in conjunction with epidural anaesthesia
      for hip and knee arthroplasty. Is it safe?
AB  - The place of indwelling urinary catheterisation following epidural anaesthesia to
      prevent acute retention of urine after hip and knee arthroplasty is
      controversial. Even with the use of aseptic techniques and closed sterile
      drainage, bacteriuria has been reported in 10-27% of catheterised patients. A
      prospective trial was carried out in 68 consecutive patients undergoing knee or
      hip joint arthroplasty with epidural anaesthesia to investigate the perioperative
      complications of short term urinary catheterisation. Following establishment of
      combined epidural and general anaesthesia, all patients underwent urinary
      catheterisation under aseptic technique by a member of the surgical team.
      Prophylactic antibiotics were given prior to insertion and continued for 24-48h
      postoperatively to minimise the risk of prosthetic infection. The mean indwelling
      urinary catheter (IDC) period was 3.6 days (range 2-14). There were three (4.4%)
      urinary tract infections (UTIs) all of which resolved with appropriate
      antibiotics. Two were detected upon removal of the urinary catheter and one was
      detected on the seventh postoperative day when symptoms were detected. No patient
      required recatheterisation. There was no other infective morbidity or wound
      infection. Our findings suggest the use of IDC for short periods combined with
      prophylactic antibiotics is safe in the perioperative phase of joint
      arthroplasty.

PMID- 11341637
TI  - Cyclic guanine monophosphate (cGMP) an intracellular mediator of cavernosal
      smooth muscle relaxation following penile vascular surgery.
AB  - BACKGROUND: We describe a new surgical method for treatment of male impotence.
      This procedure allows preservation of erectile tissues and avoids the need for
      implantable devices. It was demonstrated, that after this procedure sustained and
      reproducible erections were feasible. The role of cyclic guanine monophosphate
      (cGMP) in generation of erection following this procedure was studied. METHODS:
      Concentration of cGMP in erectile tissues was studied in the chronic canine
      experimental model. cGMP measurements were obtained using enzymeimmunoassay
      method. RESULTS: It was detected that the process of erection was accompanied
      with increased concentration of cGMP in the involved erectile structures (from
      39.59 +/- 8.95 and 39.39 +/- 8.54 pm/g to 78.67 +/- 24.05 and 81.62 +/- 18.80
      pm/g respectively with p = 0.0001). Concentration of cGMP did not change in the
      control (from 41.14 +/- 5.38 to 39.26 +/- 7.59 pm/g with p = 0.4568). CONCLUSION:
      It can be concluded, that proposed new surgical procedure causes erection not by
      simple distention of erectile tissue sinuses by arterial blood. Arterial blood
      inflow is accompanied by activation of intracellular mechanisms responsible for
      smooth muscle relaxation in erectile tissues. Normal values of cGMP concentration
      in canine erectile tissues are also reported.

PMID- 11341638
TI  - Calcium signaling pathways in the enteric nervous system.
AB  - The intracellular calcium level is an important regulator of cellular
      functioning, and its tight regulation occurs at several levels. Influx of
      extracellular calcium occurs via voltage-gated channels in response to a
      depolarization, and "capacitative" extracellular calcium occurs with cellular
      calcium depletion. Intracellular release of calcium also occurs through both the
      inositol trisphosphate- and ryanodine-sensitive stores of calcium. The following
      will detail these events and recent discoveries in Ca2+ signaling, and will
      specifically focus on their role in the functioning of the enteric nervous
      system.

PMID- 11341639
TI  - Assessment of skeletal muscle damage in experimental animal using In-111
      antimyosin.
AB  - Skeletal muscle injury induced in the thigh muscles of New Zealand rabbits was
      investigated using radionuclide imaging technique after intravenous injection of
      In-111 antimyosin. Images were obtained for 3 weeks beginning from the first day
      of injury. The injury was visualized as early as 3 h after injection of the
      tracer. The mean uptake ratio of the injury to the normal muscle was 2.8 +/- 0.62
      (p < 0.001) on the third to fifth day, decreasing with healing to 1.40 +/- 0.15
      by the end of the study (3 weeks). The mean uptake ratio of the more severely
      crushed left to less severely crushed right side was 1.36 +/- 0.17 (p < 0.01) on
      the third day. The results of this study show that the radionuclide imaging
      technique using In-111 antimyosin is useful for the assessment of skeletal muscle
      damage and also for monitoring the progress of healing. This technique can be
      applied clinically to evaluate skeletal muscle damage in problematic fractures.

PMID- 11341640
TI  - Enhanced expression of transforming growth factor (TGF) -alpha precursor and TGF
      beta1 during Paneth cell regeneration.
AB  - An intravenous injection of diphenylthiocarbazone (dithizone), a zinc chelator,
      induces selective killing and rapid regeneration of Paneth cells, which have a
      large amount of zinc in their cytoplasmic granules. We examined the expression
      pattern of transforming growth factor (TGF) -alpha and TGF-beta1 in this
      regenerative process. Messenger RNA expression of TGF-alpha and TGF-beta1 reached
      their peaks at 12 and 24 hr after dithizone injection, respectively. Protein
      expression of TGF-alpha precursor and TGF-beta1 increased to a maximum at 24 and
      72 hr, respectively. Their immunoreactivities were localized in the epithelial
      cells in the vicinity of Paneth cells, whereas they were prominent in the upper
      half of the crypts in control rats. In conclusion, destruction of Paneth cells
      induced TGF-alpha precursor expression, followed by an increase of TGF-beta1
      especially in the crypt bases. This unique expression pattern of two growth
      factors may be involved in rapid regeneration of Paneth cells.

PMID- 11341641
TI  - Does bovine lactoferrin inhibit Helicobacter pylori?

PMID- 11341642
TI  - Gastric phytobezoar: treatment using meat tenderizer.
AB  - In summary bezoars are rarely symptomatic. CT scan of the abdomen is rapidly
      becoming the first tool of diagnosis, while endoscopy still remains the best
      diagnostic test. Medical treatment is usually successful, as in this case and
      rarely do patients require surgery.

PMID- 11341643
TI  - A novel isoform of human fibroblast growth factor 8 is induced by androgens and
      associated with progression of esophageal carcinoma.
AB  - Human esophageal carcinomas occur more frequently in males, suggesting that
      androgens may play a role in the regulation of gene expression associated with
      malignant transformation. We previously established an androgen-sensitive
      squamous cell carcinoma line, KSE-1, from a male patient with esophageal cancer;
      recently a novel isoform of human fibroblast growth factor 8 (FGF8f, isoform
      FGF8b) was identified and expressed following androgen stimulation of KSE-1
      cells. The predicted amino acid sequence of FGF8f contained an additional 29
      amino acids when compared to FGF8b. Flutamide, an androgen antagonist, inhibited
      both FGF8b and FGF8f transcription in a dose-dependent manner. Tissue analysis
      from tumors revealed FGF8b expression in 24 of 41 male, but in 0 of 9 female
      esophageal carcinomas (58.5%), and none in adjacent normal esophageal mucosa. In
      addition, FGF8f was detected in 9 of 24 FGF8b-positive tumors (37.5%), and this
      observation was significantly associated with a poor prognosis (P < 0.001). Our
      observations suggest that androgenic exposure will induce FGF isoforms in tumor
      cells, and expression of these growth factors is associated with the prevalence
      and prognosis of esophageal carcinoma in males.

PMID- 11341645
TI  - Refractory pancreatitis secondary to ruptured hepatocellular carcinoma into the
      common bile duct.

PMID- 11341644
TI  - Risk factors for hepatocellular carcinoma in Turkey.
AB  - The contribution of hepatitis B, hepatitis C, and excess alcohol intake to the
      development of hepatocellular carcinoma in Turkey was assessed. The study was
      conducted through a questionnaire sent to seven major medical referral centers in
      different regions of Turkey and is based on 207 patients seen in the period 1994
      1997. Of the seven centers, two were located in West Turkey (54 patients), two
      were in Central Turkey (85 patients), and two were in south and southeast Turkey
      (68 patients). In 196 of the 207 patients (94.7%), there was a history of chronic
      liver disease, and in 180 patients (87%) liver cirrhosis was documented. Of the
      207 patients, 116 (56%) had hepatitis B, 48 (23.2%) had hepatitis C, and 33
      (15.9%) had a history of excess alcohol intake. Anti-delta testing was available
      in 69 of 116 patients with hepatitis B, and anti-HDV was positive in 13 of these
      patients (13/69, 18.8%). Of the 33 patients with a history of heavy alcohol
      intake, 18 had concomitant chronic viral hepatitis infection, and alcohol alone
      was the etiology of hepatocellular carcinoma in only 15 cases (7.2%). The
      distribution of etiologic factors was not homogenous in different geographical
      regions in Turkey. In central, south, and southeastern Turkey, the predominant
      etiology of hepatocellular carcinoma was hepatitis B, whereas in western Turkey
      the impact of hepatitis B, hepatitis C, and alcohol was similar. This study
      indicates that hepatitis B virus infection is the leading cause of hepatocellular
      carcinoma in Turkey, followed by hepatitis C infection and alcoholic liver
      disease.

PMID- 11341646
TI  - Groove pancreatitis: an important differential diagnosis to malignant stenosis of
      the duodenum.

PMID- 11341647
TI  - Synergies of heparin and second messengers pathways involved in tissue-specific
      gene expression in hepatocytes.
AB  - We have investigated the effect of soluble or extracellular-matrix (ECM) -bound
      heparin in conjunction with various second messenger pathways on cell
      proliferation and tissue-specific gene expression in primary cultures of
      hepatocytes. None of the combinations of heparin and second messenger stimulators
      or inhibitors had an effect on hepatocyte proliferation. Soluble heparin enhanced
      albumin expression in hepatocytes. Activation of protein kinase C, as well as an
      increase in intracellular cAMP, abolished this increase in albumin expression in
      the presence of heparin. When hepatocytes were plated on hepatocyte-derived ECM,
      containing highly sulfated heparan sulfate chains, activation of protein kinase C
      and an increase in intracellular cAMP strongly reduced albumin expression in
      hepatocytes. When heparan sulfate chains were removed from the ECM by heparinase
      treatment, activation of protein kinase C and increased cAMP were less inhibitory
      for albumin expression in hepatocytes. Inhibition of tyrosine kinases did not
      affect the induction of albumin mRNA by heparin. We conclude that heparin induces
      albumin expression in hepatocytes and activation of protein kinase C or increased
      intracellular cAMP antagonize this effect. ECM-bound heparan sulfates do not act
      in the same manner as soluble heparin.

PMID- 11341648
TI  - Development and characterization of a hybrid bioartificial liver using primary
      hepatocytes entrapped in a basement membrane matrix.
AB  - For the development of a bioartificial liver (BAL) support device, it is most
      important to establish highly differentiated liver cells cultured at high
      density. When rat hepatocytes were cultured on a basement membrane matrix,
      Engelbreth-Holm-Swarm (EHS) gel, their rates of albumin secretion were very high,
      as measured by ELISA, and these high rates were maintained for more than three
      weeks of culturing. This level of activity greatly exceeded that of hepatocytes
      cultured on a plastic substratum, poly-N-p-vinylbenzyl-D-lactonamide (PVLA), on a
      single layer of collagen, or in a collagen sandwich culture. In an in vitro
      perfusion experiment, rat hepatocytes rapidly and completely removed ammonia from
      Eagle's MEM supplemented with 0.2 mM NH4Cl, although ammonia levels of the medium
      serially increased in modules containing HepG2 cells. A hybrid liver support
      system was developed and consisted of plasma perfusion through porous hollow
      fiber modules inoculated with 10 billion porcine hepatocytes entrapped in EHS
      gel. This system was applied to pigs with ischemic liver failure 8 hr after
      creation of a portocaval shunt and hepatic devascularization. In animals treated
      with the BAL support system, blood bicarbonate levels were increased immediately
      after treatment, and hemodynamic stability was improved. In control pigs, on the
      other hand, blood bicarbonate levels and blood pressure remained low. Plasma
      levels of ammonia and lactate decreased in pigs treated with the BAL device, but
      not in control animals. These results indicate that primary hepatocytes
      outperform HepG2 cells as a source of biotransformation functions in a BAL system
      and that the use of a BAL support device in combination with a hollow fiber
      module and hepatocytes entrapped in EHS gel has potential advantages for clinical
      use in patients with fulminant hepatic failure.

PMID- 11341649
TI  - Oxygen free radical production in rat liver: dose-related effect of ethanol on
      reperfusion injury.
AB  - Ethanol is known to have a deleterious effect on liver ischemia-reperfusion
      injury, but recent reports suggest that light ethanol consumption may produce a
      protective effect in several organs. We aimed to investigate effects of different
      doses of ethanol on liver oxidative injury. Rats were fed with ethanol-containing
      diets (24, 30, 36, 40% for groups A, B, C, D, respectively). After four weeks,
      livers were exposed to ischemia-reperfusion. Chemiluminescence was recorded;
      total lipids, adenosine triphosphate, malondialdehyde, reduced glutathione and
      lactic dehydrogenase were assessed. In all groups, ischemia resulted in the
      disappearance of O2*-, a decrease in glutathione and adenosine triphosphate, and
      stable malondialdehyde values. During the reperfusion phase, O2*- production,
      malondialdehyde and lactic dehydrogenase increased, reaching significantly higher
      values in groups C and D and significantly lower values in group B. The effect of
      ethanol on ischemia-reperfusion injury seems to be a dose-related response, with
      an additional toxic effect only at high doses of ethanol.

PMID- 11341650
TI  - Combined therapy with interferon and ribavirin in chronic hepatitis C does not
      affect serum quasispecies diversity.
AB  - Our aim was to investigate if interferon plus ribavirin has any effect on serum
      HCV quasispecies distribution and the relationship between diversity of HCV
      quasispecies and treatment response. In all, 21 patients were treated with
      interferon plus ribavirin for 48 weeks. The presence of HCV quasispecies was
      determined in serum samples at baseline and at the fourth week of treatment by
      SSCP analysis of the hypervariable region. SSCP pattern was defined as single or
      multiple band. A single band was found in six patients and multiple bands in
      nine. No significant difference was found between SSCP pattern in pretreatment
      samples and response to the therapy. In none of the patients were observed
      changes in number of SSCP bands between samples taken at baseline and in the
      fourth week of the therapy. In conclusion, the complexity of HCV quasispecies
      before the therapy was not related to treatment response; combined therapy did
      not affect serum HCV quasispecies.

PMID- 11341651
TI  - Nitric oxide and chronic HCV and HIV infections.
AB  - High concentrations of nitric oxide (NO) are generated by the inducible form of
      the enzyme nitric oxide synthase (iNOS), which is expressed in activated
      macrophages and in hepatocytes. Increased expression of iNOS in hepatocytes or
      macrophages might be expected in chronic HCV liver disease and HIV infections.
      This might in turn be reflected in increased serum NO levels in these two
      conditions. In view of the discrepant findings in published reports, we measured
      serum NO levels in a large number of chronic HCV-infected patients and patients
      with chronic HIV infections with or without AIDS-related opportunistic infection.
      We also localized HCV and iNOS antigens by immunohistochemistry, in liver biopsy
      tissue from patients with chronic HCV-related hepatitis, HCV-related cirrhosis,
      and HCV-related hepatocellular carcinoma. A group of 121 subjects with
      serological evidence of HCV with or without HIV infection were studied. These
      were compared with 14 controls without HIV or HCV disease (group A). Among the
      subjects with HCV, 35 were negative for HIV (group B), 66 were HIV positive
      (group C), and 20 had AIDS-related opportunistic infection (group D). The serum
      NO concentration was determined by the Brucine method. A well-characterized
      commercially available antibody (HCV88) directed against a synthetic NS3 peptide
      fragment of HCV, which localizes to the hepatocyte nuclei, and an antibody to
      human macrophage iNOS, were both used to detect these proteins in liver biopsy
      tissue by immunohistochemistry. Mean serum NO values in HIV negative/HCV negative
      control patients (group A) (54.6+/-12 microM) were similar to those in HIV
      negative/HCV positive patients (group B) (55.0+/-13 microM) and HIV positive
      without AIDS-related disease/HCV positive patients (group C) (47.2+/-25 microM).
      By contrast, the mean serum NO (70.1+/-24 microM) was significantly increased in
      HCV-positive patients with AIDS-related infection (group D) compared to controls
      (P = 0.02). HCV NS3 and iNOS antibody staining hepatocytes were not detected in
      any of the control non-HCV-infected biopsy samples. In early chronic HCV
      hepatitis (fibrosis scores F0-F2), HCV NS3 antigen localized focally to only a
      small number of hepatocytes. In cirrhosis (fibrosis score F4) with or without
      hepatocellular carcinoma, the majority of hepatocyte nuclei stained positively
      with HCV NS3 antibody. The majority of hepatocytes in chronic HCV hepatitis
      expressed iNOS, irrespective of histological disease severity. The staining was
      present uniformly in the cytoplasm. In chronic HCV and HIV coinfection, the
      pattern and number of iNOS staining cells were similar to that in patients with
      chronic HCV infection alone. In conclusion, there is widespread expression of
      iNOS in hepatocytes in chronic HCV liver disease, irrespective of liver disease
      stage. However, elevated NO levels in serum were related only to active AIDS
      related bacterial, protozoan, and fungal infections, rather than to chronic viral
      infection with HCV or HIV alone. NO may play a role in the local control of
      chronic viral infections at tissue level, but this is not reflected in serum
      levels.

PMID- 11341652
TI  - Small intestine bacterial overgrowth and metabolic bone disease.
AB  - Small intestine bacterial overgrowth is a malabsorption syndrome and, therefore,
      it may contribute to the occurrence of metabolic bone disease. However, studies
      that evaluate the magnitude of this problem and the potential underlying
      mechanisms are still needed. Fourteen patients with bacterial overgrowth and 22
      comparable healthy volunteers took part in this study. All patients were affected
      by conditions known to predispose to bacterial overgrowth. Diagnosis was based on
      the following criteria: increased breath hydrogen levels in the fasting state
      and/or increased breath hydrogen excretion after the ingestion of 50 g of glucose
      solution, improvement after a 10-day course of antibiotic therapy of severity of
      symptoms and of H2 excretion parameters. Measurement of bone mineral density by
      dual-energy x-ray absorptiometry at lumbar spine and femoral level and evaluation
      of nutritional status were performed. Physical activity, sunlight exposure, and
      cigarette smoking were also evaluated. Patients showed lumbar and femoral bone
      mineral density values significantly lower than control group; also the
      prevalence of bone loss at both lumbar and femoral levels was higher in patient
      group than in healthy volunteers. Body mass index was significantly lower in
      patients than in healthy volunteers. Lumbar and femoral bone mineral density were
      significantly correlated and both correlated with body mass index and with
      duration of symptoms. No correlation between BMD values and physical activity,
      sunlight exposure, and cigarette smoking was evident. Our results show that small
      intestine bacterial overgrowth is an important cofactor in the development of
      metabolic bone disease. The severity of bone loss is related to poor nutritional
      status and duration of malabsorption symptoms.

PMID- 11341653
TI  - Epithelial proliferation and ras p21 oncoprotein expression in rectal mucosa of
      patients with ulcerative colitis.
AB  - In ulcerative colitis (UC), epithelial proliferation plays a role in crypt repair
      and neoplastic evolution. Proliferative status is predominantly connoted in
      active disease, but not defined in remission. Histologically, remission is
      characterized by normalization of the picture or development of atrophy. Mutation
      of the ras oncogene is involved in intestinal carcinogenesis. Aim of this work
      was to assess the proliferative pattern of rectal epithelium in UC during disease
      activity and in remission and correlate it with ras oncoprotein p21. The study
      was performed retrospectively in rectal biopsies from four groups each of 10
      patients: active ulcerative colitis (AUC), remission with a normal histology
      (RUC), remission with rectal atrophy (ARUC), and irritable bowel syndrome (C,
      control group). In all, immunohistostain was employed to evaluate the
      proliferation cell nuclear antigen labeling index (PCNA LI) and ras p21.
      Statistical analysis was performed by ANOVA and Student-Neumann-Keuls tests. PCNA
      LI was significantly higher in AUC and ARUC than in RUC and C. Positive cells
      were predominant in the lower zone of crypts in RUC and C, while a significant
      expression of PCNA was also observed in the upper areas in AUC and ARUC.
      Oncoprotein p21 was expressed on the apical surface of the epithelium in 3/10 AUC
      patients, in all 10 ARUC patients and in none of RUC and C. The persistently
      increased epithelial proliferation associated with ras p21 expression in ARUC may
      be due to the action of an abnormal, mutated ras gene that could play a role in
      UC-related tumorigenesis.

PMID- 11341654
TI  - Effect of iron supplementation on oxidative stress and intestinal inflammation in
      rats with acute colitis.
AB  - In this study, we investigated the effect of intraperitoneal iron dextran (100
      mg/100 g body weight) on oxidative stress and intestinal inflammation in rats
      with acute colitis induced by 5% dextran sulfate sodium. In both colitis and
      healthy animals, disease activity index, crypt and inflammatory scores, colon
      length, plasma and colonic lipid peroxides, and plasma vitamins E, C, and retinol
      were assessed. The results showed that iron-supplemented groups had moderate iron
      deposition in the colonic submucosa and lamina propria. In the colitis group
      supplemented with iron, colon length was significantly shorter; disease activity
      index, crypt, and inflammatory scores and colonic lipid peroxides were
      significantly higher; and plasma alpha-tocopherol was significantly lower
      compared to the colitis group without iron supplementation. There was no
      intestinal inflammation and no significant increase in colonic lipid peroxides in
      healthy rats supplemented with iron. In conclusion, iron injection resulted in an
      increased oxidative stress and intestinal inflammation in rats with colitis but
      not in healthy rats.

PMID- 11341655
TI  - Peyer's patches epithelium in the rat: a morphological, immunohistochemical, and
      morphometrical study.
AB  - The epithelial layer covering lymphoid follicles of Peyer's patches consists of
      cells with a different surface morphology. Some of these cells have been
      described as a distinct cytotype, the so-called M cells. In order to resolve the
      controversy on the specific morphological and biochemical markers of M cells,
      structural, ultrastructural, and morphometrical study of the epithelium covering
      the rat Peyer's patches were performed. Peyer's patches from healthy rats were
      processed for light microscopy, immunohistochemistry, in situ nick-end labeling
      (TUNEL), and scanning and transmission electron microscopy. A morphometric study
      was also performed to evaluate microvillus density, length, and number of
      lysosomes in different areas of the epithelium. Peyer's patches were covered by
      simple columnar/cubical dome epithelium (DE). Scarce goblet cells and a large
      number of enterocytes were observed. Ultrastructural observations revealed that
      the DE showed cells with different morphology. The density and length of
      microvilli and the lysosome number varied along the whole dome without
      significant differences. The DE cells characterized by short and disorganized
      microvilli appeared always in close spatial relationship with lymphocytes. In
      conclusion, the concept that distinct cell types (enterocytes and M cells) can be
      identified in the rat DE does not appear to be valid based on morphological
      criteria. It seems correct to consider that in rat Peyer's patches the presence
      of scarce goblet cells and a large number of enterocytes showing dynamic
      morphofunctional modifications is related to the functional state and/or to cell
      cycle.

PMID- 11341656
TI  - Stimulation of non-sodium-dependent water, electrolyte, and glucose transport in
      rat small intestine by gum arabic.
AB  - In experimental models of gastroenterological disease, the soluble fiber gum
      arabic (GA) acts as a proabsorptive adjuvant. This study investigated which
      specific transport pathway(s) are affected by GA. Rat jejunum was perfused under
      anesthesia with a standardized oral rehydration solution (ORS) containing D
      glucose, with or without GA (2.5 g/liter). In some preparations either
      phloridizin, a competitive inhibitor of Na+-coupled D-glucose transport, or
      phloretin, an inhibitor of basolateral glucose transport, were added to the ORS,
      with or without GA. Diffusion and paracellular transport changes due to GA were
      evaluated with L-glucose and [14C]polyethlyene glycol 4000 (PEG). GA partially
      reversed water, Na+, and D-glucose absorption inhibition induced by phloridzin
      and normalized water and Na+ absorption in the presence of phloretin. GA also
      increased absorption of water, Na+, and PEG from an L-glucose ORS. The data
      suggest that GA does not act via Na+ dependent mechanism(s), but stimulates
      transcellular and/or transjunctional transport pathways; therefore GA may be
      useful to increase absorption of solutes transported by diffusion.

PMID- 11341657
TI  - Effect of lipopolysaccharide on small intestinal L-leucine transport in rabbit.
AB  - In the present study, we have investigated whether the lipopolysaccharide (LPS)
      endotoxin from Escherichia coli is able to alter the jejunal transport of L
      leucine when the tissue is exposed to endotoxin. The results have shown that the
      LPS at 3 x 10(-5) microg/ml decreases the uptake of L-leucine into the
      enterocyte, as well as the mucosal to serosal flux of L-leucine. The secretagogue
      effect of LPS on the gut did not affect the inhibitory effect of LPS on the
      intestinal absorption of the amino acid. The endotoxin did not modify amino acid
      diffusion across the intestinal epithelium. However, from the mediated transport,
      only the Na+-dependent transport system was affected by LPS with a diminution of
      the transporter affinity (the apparent Km was increased). In addition, we found a
      reduction of the Na+, K+-ATPase activity, which could explain the L-leucine Na+
      dependent transport inhibition.

PMID- 11341658
TI  - Time course of spontaneous bacterial translocation from gastrointestinal tract
      and its relationship to intestinal microflora in conventionally reared infant
      rats.
AB  - Whereas the developed gut mucosal barrier prevents luminal bacteria from invading
      the host, bacterial translocation appears to be facilitated in the neonate. The
      aim of this study was to determine the extent to which bacteria spontaneously
      translocate from the gut to extraintestinal organs during the neonatal period and
      to relate translocation to the evolving intestinal flora in the rat. Newborn
      Sprague-Dawley rats suckled ad libitum and ate regular chow after weaning. A
      total of 167 rats were killed either immediately or at 1, 9, 14, 21, 26, or 42
      days after delivery. Mesenteric lymph nodes (MLN), liver, heart blood, and the
      terminal ileal loop were harvested under sterile conditions and analyzed for
      aerobic and facultatively anaerobic bacteria by standard microbiologic
      procedures. Bacterial translocation to the MLN and liver began soon after birth
      and peaked during the second week. On day 14, translocation to any organ was
      present in 85% of rats. All cultures from the liver were sterile after day 26. By
      contrast, the fall in translocation to the MLN was incomplete, as 50% of pups
      still had positive MLN on day 42. Blood cultures were positive in three of the
      167 rats. The intensity of translocation as determined by the number of organs
      infected significantly increased with the number of gram-negative enterics and
      gram-positive cocci in the gut and was negatively correlated with the percentage
      of lactobacilli from the total measured intestinal flora (P < 0.0001). In
      conclusion, bacterial translocation from the gut is a physiological and age
      dependent phenomenon in the neonatal rat. Translocation appears to be facilitated
      when intestinal concentrations of gram-negative enterics and gram-positive cocci
      are high and when the concentration of lactobacilli is low.

PMID- 11341659
TI  - Acute pancreatitis and bacterial translocation.
AB  - Infectious complications are the most frequent and severe complications of acute
      narcotizing pancreatitis (AP) with a mortality rate up to 80%. Although
      experimental and clinical studies suggest that the microbiologic source of
      pancreatic infection could be enteric, information in this regard is scant. This
      study evaluated bacterial translocation (BT) using mild and severe models of AP.
      Mild AP was induced by 6-hr continuous intravenous infusion of cerulein, while
      severe AP was induced by additional infusion of glycodeoxycholic acid into the
      biliopancreatic duct. BT was evaluated with organ cultures performed when animals
      were killed (24 hr). To confirm the gastrointestinal origin of the translocating
      microorganisms, fluorescent microspheres were also given to the animals in
      drinking water 24 hr before induction of AP. At the time of death beads were
      counted with a (fluorescence-activated cell sorter) (FACS) in peritoneal lavages
      and with fluorescent microscopy in frozen sections of the pancreata. Morphology
      of the distal small bowel showed significant changes in the animals with AP
      compared to controls, such as reduction of villus high and altered
      microvasculature. Mild AP induced BT to the pancreas in 100% of the animals,
      compared to pancreata from control groups. Severe AP induced increased BT to the
      pancreas. BT to liver and spleen was also significantly increased with AP. The
      presence of fluorescent microspheres confirmed their enteric derivation. This
      study provides evidence for the enteric origin of microorganisms responsible for
      pancreatic infectious complications during AP. The evidence of BT after
      laparotomy suggests an increased risk of infections with the association of these
      conditions. This could provide an explanation for the high mortality associated
      with laparotomy in course of AP.

PMID- 11341661
TI  - Necrotizing fasciitis of abdominal wall in AIDS.
AB  - Necrotizing fasciitis (NF) is an uncommon but potentially lethal soft-tissue
      infection. Mortality rate is high and has not changed since it was first
      described by Meleny. Although immunodeficiency is a risk factor for NF, there is
      only one reported case of NF in AIDS involving the cervical region. We report the
      first case of necrotizing fasciitis of the abdominal wall in an AIDS patient.

PMID- 11341660
TI  - Lack of evidence for small intestinal mucosal T-cell activation as a pathogenic
      mechanism in African HIV-associated enteropathy.
AB  - The role of mucosal T-cell activation in HIV-associated enteropathy is uncertain.
      Twenty Zambian patients with AIDS and chronic diarrhea were studied, as were nine
      controls. Distal duodenal biopsies were taken at endoscopy. Morphometric analysis
      and dual color immunofluorescence staining were performed. Villous height was
      reduced [177 (118-228) vs 305 (244-358) microm P = 0.002] and crypt depth
      increased [220 (164-202) vs 194 (164-202) microm P = 0.008] in AIDS patients
      compared to controls. CD3+CD4+ T cells were reduced in AIDS patients compared to
      controls [12.9 (5.7-25.2) vs 47.6 (33.4-65.5)% P = 0.04]. There was no
      significant difference in expression of CD8, CD25, CD69, HML-1, or HLA-DR on T
      cells between the AIDS patients and controls, with the exception of CD3+HML-1+
      cells, which were increased in AIDS patients (P = 0.05). Small intestinal T-cell
      activation was similar between AIDS patients and controls. We conclude,
      therefore, that this mechanism is not likely to be important in the pathogenesis
      of HIV-associated enteropathy.

PMID- 11341662
TI  - Mechanisms of cisapride affecting gallbladder motility.
AB  - Regulation of gallbladder motility is complex. Mechanisms via which cisapride may
      interact with gallbladder function are being reviewed. These are multiple and
      include direct effects on gallbladder and the sphincter of oddi, as well as
      indirect effects involving gastro-intestinal hormone levels, gastric emptying,
      gallbladder refilling, interdigestive migrating motor cycle (IMMC) and small
      intestinal transit. Effects, moreover, may vary according to dose, route and
      duration of cisapride administration, which may explain conflicting data so far
      with cisapride.

PMID- 11341663
TI  - Effect of coffee on motor and sensory function of proximal stomach.
AB  - Some people attribute dyspeptic symptoms to drinking coffee, suggesting that
      coffee affects one or more functions of the proximal gastrointestinal tract. In a
      randomized controlled, cross-over, single-blinded study, the effects of coffee on
      gastric relaxation, gastric wall compliance and sensations, elicited by
      distension, were investigated in 10 healthy volunteers. Using the barostat
      technique, volume changes of an intragastric bag were recorded for 20 min after
      intragastric administration of 280 ml of coffee or water. Then, after deflation,
      the volume of the bag was increased stepwise every 3 min to assess gastric wall
      compliance and wall tension. At the end of every volume step, sensations (nausea,
      pain, and bloating) were scored. During the first 20 min after coffee
      administration, the volume change of the intragastric bag was larger than after
      water (P < 0.05). There were no differences in gastric wall compliance, wall
      tension, or symptom scores. In conclusions, coffee, in comparison with water,
      enhances the adaptive relaxation of the proximal stomach, but has no effect on
      its wall compliance, wall tension, or sensory function.

PMID- 11341664
TI  - Effect of vincristine on gastric motility in conscious rats.
AB  - We investigated the possible involvement of the upper alimentary tract in
      vincristine (VCR)-induced dysmotility. Gastric contractions were recorded by a
      strain-gauge force transducer in conscious rats. Rats were injected with various
      doses of VCR followed by continuous recording for 12 hr. Additionally, 3-hr
      recordings to study the later effects were performed one and three days after
      injection. Gastric motility was dose-dependently increased by VCR. Post- versus
      preinjection motility index (MI; area under contraction waves) ratios were 0.78+/
      0.12 for saline and 1.95+/-0.21 for VCR at 0.75 mg/kg. This increase in MI was
      completely inhibited by atropine and hexamethonium. MI one day after injection of
      VCR (0.75 mg/kg) was significantly less than in control (0.32+/-0.10 vs 0.92+/
      0.24, respectively). The decrease was reversed by acetylcholine. In conclusion,
      VCR first increased gastric motility, and this was followed by a gradual decrease
      in conscious rats. These alterations may involve a presynaptic cholinergic
      pathway.

PMID- 11341665
TI  - Tension-strain relations and morphometry of rat small intestine in experimental
      diabetes.
AB  - Tension-strain relations and morphometric data were studied in isolated segments
      of the jejunum and distal ileum in untreated diabetic rats, insulin-treated
      diabetic rats, and nondiabetic control rats. Diabetes was induced by a single
      intravenous injection of streptozotocin (28 mg/kg body wt). All injected rats
      developed hyperglycemia. The experiment was terminated after 28 days and the
      intestinal segments were superfused with saline solution containing papaverine to
      abolish contractile activity. Stepwise inflation of a balloon in which the cross
      sectional area (CSA) was measured provided the luminal pressure-loading stimulus.
      The circumferential tension-strain relation was derived from steady-state values
      of internal radius and applied pressure. The intestinal weight, length, and
      weight per unit length increased significantly in untreated diabetic rats
      compared to the two other groups (P < 0.05). The body weight decreased in
      untreated diabetic rats compared to the two other groups (P < 0.05). The pressure
      CSA relations differed between jejunum and distal ileum (P < 0.001) but not
      between the groups (P > 0.2). The tension-strain relations in jejunum and distal
      ileum were nonlinear and the curves for the two diabetic groups were shifted to
      the left compared to the curve for controls (P < 0.05), indicating increased wall
      stiffness. The histomorphometric data showed increased wall thickness in
      untreated diabetic rats compared to the two other groups both in jejunum and
      distal ileum (P < 0.02). Mucosal, submucosal, and muscle layer thicknesses did
      not differ between the three groups. No significant association was found between
      the histomorphometric and biomechanical parameters.

PMID- 11341666
TI  - Matrix composition in opossum esophagus.
AB  - The esophagus of mammalian species is organized into mucosa, connective tissue,
      and muscle, but little is known about the matrix of these layers. We studied by
      immunohistochemistry the distribution of collagens, fibronectin, versican, and
      elastin in the smooth muscle segment of the American opossum. Cryosections were
      exposed to specific antibodies and fluorescent-stained using conjugates of
      rhodamine or isothiocyanate. Staining was scored by two observers. We found that
      collagen I was prominent in the submucosa and in the muscular septa; collagen III
      formed fibrillar meshes in the lamina propria and the submucosa but was virtually
      absent from the epithelial and muscular layers; collagen IV was restricted to the
      base of the epithelium; collagen V, in contrast to collagen III, was prominent in
      epithelium and muscularis mucosae and sparse in muscular septa and submucosa.
      Fibronectin distribution followed collagen III; it formed layers in lamina
      propria and submucosa and strands in muscle septa and between individual muscle
      cells. Versican distribution followed collagen V; it was prominent in large
      muscle septa and formed thick sheets at the boundaries of submucosa/circular
      muscle and of circular/longitudinal muscle. We also determined the tissue
      contents of protein, hexuronic acid, and fibronectin. The mucosal layers exceeded
      the muscular layers in their content of hexuronic acid and fibronectin but not
      protein. We conclude that individual layers of the smooth muscle esophagus each
      have their own characteristic matrix. Lamina propria and submucosa are similar
      with regard to fiber orientation but lamina propria contains relatively more
      collagen III (small fibril) and submucosa comparatively more collagen I (large
      fibril). Nonfibrillar collagen V and versican are particularly prominent
      specifically on the boundaries between contracting muscle tissue and connective
      tissue framework.

PMID- 11341667
TI  - Protective effect of ammonia against reflux esophagitis in rats.
AB  - Although several recent studies have reported that curing Helicobacter pylori (H.
      pylori) may result in the development of reflux esophagitis (RE), the mechanisms
      leading to this complication are unknown. One by product of H. pylori infection
      is ammonia, which serves as an acid neutralizer. The aim of this study was to
      clarify whether ammonia, which is produced during H. pylori infection, has a
      protective effect on the esophagus. Eight-week-old male Sprague-Dawley rats were
      fasted for 24 hrs. Under anesthesia, both the pylorus and limiting ridge were
      simultaneously ligated. One hour postligation, 0.3 ml of saline or ammonia at
      various concentrations was administered intragastrically by gastric intubation.
      Three hours after ligation, the animals were killed, the esophagus and stomach
      were removed, and the length of esophageal hemorrhagic erosions was measured. The
      incidence of RE was 100% (7/7) in the control group, 71% (5/7) in the low-ammonia
      group, 29% (2/7) in the middle-ammonia group, and 14% (1/7) in the high-ammonia
      group. The severity of lesions decreased in correspondence to increases in
      ammonia concentration. The development of RE was significantly inhibited by
      ammonia in a dose-dependent manner. This study indicates that ammonia protects
      against development of RE. A decreased amount of ammonia in the stomach might be
      related to the development of RE after H. pylori eradication therapy.

PMID- 11341668
TI  - Ischemic necrosis of gastric wall after long-term ergotamine pill abuse: case
      report and review of the literature.

PMID- 11341669
TI  - Double-blind, placebo-controlled trial of famotidine in children with abdominal
      pain and dyspepsia: global and quantitative assessment.
AB  - To determine the benefit of using an H2-receptor antagonist in children with
      abdominal pain and dyspepsia, 25 such children were enrolled in a double-blind,
      placebo-controlled trial of famotidine. Global and quantitative pain assessments
      were done before and after each treatment period. The quantitative assessment was
      calculated based on the abdominal pain score that was the sum of three
      components. Based on the global evaluation, there was a clear benefit of
      famotidine over placebo (68% vs 12%). Using the quantitative assessment, however,
      the mean improvement of the score using famotidine versus placebo was not
      statistically significant (3.37+/-3.53 vs 1.66+/-2.7). There was a significant
      improvement in this score during the first treatment period regardless of
      medication used (period effect: P = 0.05). A subset of patients with peptic
      symptoms demonstrated a significant drug effect that outweighed the period effect
      (drug effect: P = 0.01; period effect: P = 0.02). We conclude that famotidine
      subjectively improves the symptoms of children with recurrent abdominal pain but
      not objectively using the derived score. However, famotidine is significantly
      more effective than placebo among children with peptic symptoms. The use of this
      simple scoring scale may facilitate selecting those children who will benefit
      from H2-receptor antagonist therapy.

PMID- 11341670
TI  - Reversible pheripheral edema in female patients taking proton pump inhibitors for
      peptic acid diseases.
AB  - Pheripheral edema was observed in five female patients after taking proton pump
      inhibitors omeprazole, lansoprazole, or pantoprazole for 7-15 days for peptic
      acid diseases in recommended standard doses. Edema disappeared two to three days
      after stopping therapy but reappeared in all five patients after being reexposed
      to the drugs. In three of the patients drug kinetic investigations were performed
      and revealed a slow metabolizer status. During dose-finding studies for
      intravenous proton pump inhibitors omeprazole and pantoprazole, three of six
      young female volunteers receiving omeprazole and two young female volunteers
      receiving pantoprazole developed peripheral edema within 8 hr when high doses of
      the proton pump inhibitors were applied by continuous infusion together with
      large volumes of fluid. The edema disappeared within 24 hr after stopping the
      infusion therapy. Serum hormone concentrations in these patients did not change
      during therapy, neither did the edema factor C1-esterase inhibitor. As a possible
      mechanism, a competitive inhibition at the receptor site of female hormones
      involved in water regulation is suspected.

PMID- 11341671
TI  - Inhibition of gastric acid secretion by saiboku-to, an oriental herbal medicine,
      in rats.
AB  - Intraduodenal saiboku-to (250-1000 mg/kg) dose-dependently reduced gastric acid
      secretion and histamine output, without altering acetylcholine output in pylorus
      ligated rats. Saiboku-to also inhibited subcutaneous bethanechol (1 mg/kg) and
      tetragastrin (0.3 mg/kg) -induced increases in gastric acid secretion in
      vagotomized pylorus-ligated rats; however, it did not inhibit subcutaneous
      histamine (20 mg/kg) -induced increase in acid secretion. These results, taken
      together, suggest a possibility that saiboku-to may inhibit histamine release.
      Thus, the effect of saiboku-to on histamine release was directly investigated by
      using anti-dinitrophenyl IgE-sensitized rat peritoneal mast cells. Antigen
      (dinitrophenyl)-induced histamine release from the mast cells was clearly dose
      dependently inhibited by saiboku-to at concentrations of 0.1-1.0 mg/ml. These
      results suggest that the inhibited gastric acid secretion with saiboku-to is due
      to inhibited histamine release.

PMID- 11341672
TI  - Teeth outside the mouth in teleost fishes: how to benefit from a developmental
      accident.
AB  - Evolution proceeds by the selection of characters that enhance survival rates so
      that the long-term outcome for a species is better adaptation to its environment.
      These new characters are "accidentally" acquired, mostly through mutations
      leading to modifications of developmental events. However, changes that lead to
      the ectopic expression of an organ are rare and, whereas their subsequent
      selection for a new role is even more rare, such a scenario has apparently
      occurred for denticles in some teleost fish. Small, conical denticles are
      present, mainly on the dermal bones of the head, in a few, unrelated lineages of
      living teleosts. Here, I show that the morphology and structure of the denticles
      in Atherion elymus, an atheriniform, is similar to those of teeth inside the oral
      cavity. These denticles are not derived evolutionarily from odontodes of early
      vertebrates, nor do they represent a re-expression as such (i.e., a long-lasting
      ability to make odontodes outside the oral cavity). Teeth and odontodes are
      homologous organs but the origin of the denticles is to be found in teeth, not in
      odontodes. The denticles are simply teeth that form outside the mouth, probably
      derived from a sub-population of odontogenically pre-specified neural crest
      cells. These "accidental" extra-oral teeth have arisen independently in these
      lineages and were selectively advantageous in a hydrodynamic context.

PMID- 11341673
TI  - Developmental system drift and flexibility in evolutionary trajectories.
AB  - The comparative analysis of homologous characters is a staple of evolutionary
      developmental biology and often involves extrapolating from experimental data in
      model organisms to infer developmental events in non-model organisms. In order to
      determine the general importance of data obtained in model organisms, it is
      critical to know how often and to what degree similar phenotypes expressed in
      different taxa are formed by divergent developmental processes. Both comparative
      studies of distantly related species and genetic analysis of closely related
      species indicate that many characters known to be homologous between taxa have
      diverged in their morphogenetic or gene regulatory underpinnings. This process,
      which we call "developmental system drift" (DSD), is apparently ubiquitous and
      has significant implications for the flexibility of developmental evolution of
      both conserved and evolving characters. Current data on the population genetics
      and molecular mechanisms of DSD illustrate how the details of developmental
      processes are constantly changing within evolutionary lineages, indicating that
      developmental systems may possess a great deal of plasticity in their responses
      to natural selection.

PMID- 11341674
TI  - Morphogenesis of the turtle shell: the development of a novel structure in
      tetrapod evolution.
AB  - The turtle shell is an evolutionary novelty that is synapomorphic for chelonians.
      The carapace is initiated by the entrapment of the ribs by the carapacial ridge
      (CR), a lateral bulge of the dorsal ectoderm and dermal mesoderm. The mechanisms
      by which the CR is initiated, the ribs entrapped and the dorsal dermis ossified,
      remains unknown. Similarly, the formation of the plastron remains unexplained.
      Here, we present a series of anatomical investigations into plastron and carapace
      formation in the red-eared slider, Trachemys scripta, and the snapping turtle,
      Chelydra serpentina. We document the entrapment of the ribs by the CR and the
      formation of the plastron and carapacial bones by intramembranous ossification.
      We note the formation of the ossification centers around each rib, which suggest
      that the rib is organizing dermal ossification by secreting paracrine factors.
      The nuchal ossification center is complex and appears to involve multiple bone
      forming regions. Individual ossification centers at the periphery of the carapace
      form the peripheral and pygial bones. The intramembranous ossification of the
      plastron proceeds from nine distinct ossification centers, and there appear to be
      interactions between the spicules of apposing centers as they draw near each
      other.

PMID- 11341675
TI  - Modularity, evolvability, and adaptive radiations: a comparison of the hemi- and
      holometabolous insects.
AB  - Despite recent attention given to the concept of modularity and its potential
      contribution to the evolvability of organisms, there has been little mention of
      how such a contribution may affect rates of diversification or how this would be
      assessed. A first key prediction is that lineages with relatively greater degrees
      of modularity in given traits should exhibit higher rates of diversification.
      Four general conditions for testing this prediction of the modular evolvability
      hypothesis are outlined here. The potential role of modularity as a deterministic
      factor in adaptive radiations is best examined by looking at historic patterns of
      diversification rather than just levels of extant diversity, the focus of most
      analyses of key innovations. Recent developmental evidence supports the notion
      that phenotypes of juvenile and adult stages of insects with "complete"
      metamorphosis (Holometabola) are distinct developmental and evolvable modules
      compared to the highly correlated life stages of insects with "incomplete"
      metamorphosis (Hemimetabola). Family-level rates of diversification for these two
      groups were calculated from the fossil record. The Holometabola was found to have
      a significantly and characteristically higher rate of diversification compared to
      the less modular Hemimetabola, consistent with the idea that intrinsic
      differences in modularity can influence the long-term evolvability of organisms.
      The modular evolvability hypothesis also makes a second key prediction: that
      characters in more modular clades will exhibit greater levels of variation due to
      their independence. This provides an independent, phenotypically based test of
      the hypothesis. We discuss here how this second prediction may be tested in the
      case of the Hemi- and Holometabola.

PMID- 11341676
TI  - Bias in the introduction of variation as an orienting factor in evolution.
AB  - According to New Synthesis doctrine, the direction of evolution is determined by
      selection and not by "internal causes" that act by way of propensities of
      variation. This doctrine rests on the theoretical claim that because mutation
      rates are small in comparison to selection coefficients, mutation is powerless to
      overcome opposing selection. Using a simple population-genetic model, this claim
      is shown to depend on assuming the prior availability of variation, so that
      mutation may act only as a "pressure" on the frequencies of existing alleles, and
      not as the evolutionary process that introduces novelty. As shown here,
      mutational bias in the introduction of novelty can strongly influence the course
      of evolution, even when mutation rates are small in comparison to selection
      coefficients. Recognizing this mode of causation provides a distinct mechanistic
      basis for an "internalist" approach to determining the contribution of mutational
      and developmental factors to evolutionary phenomena such as homoplasy,
      parallelism, and directionality.

PMID- 11341677
TI  - Phenotypic and dynamical transitions in model genetic networks. I. Emergence of
      patterns and genotype-phenotype relationships.
AB  - Genotype-phenotype interactions during the evolution of form in multicellular
      organisms is a complex problem but one that can be aided by computational
      approaches. We present here a framework within which developmental patterns and
      their underlying genetic networks can be simulated. Gene networks were chosen to
      reflect realistic regulatory circuits, including positive and negative feedback
      control, and the exchange of a subset of gene products between cells, or within a
      syncytium. Some of these networks generate stable spatial patterns of a subset of
      their molecular constituents, and can be assigned to categories (e.g., "emergent"
      or "hierarchic") based on the topology of molecular circuitry. These categories
      roughly correspond to what has been discussed in the literature as "self
      organizing" and "programmed" processes of development. The capability of such
      networks to form patterns of repeating stripes was studied in network ensembles
      in which parameters of gene-gene interaction were caused to vary in a manner
      analogous to genetic mutation. The evolution under mutational change of
      individual representative networks of each category was also simulated. We have
      found that patterns with few stripes (< or =3) are most likely to originate in
      the form of a hierarchic network, whereas those with greater numbers of stripes
      (> or =4) originate most readily as emergent networks. However, regardless of how
      many stripes it contains, once a pattern is established, there appears to be an
      evolutionary tendency for emergent mechanisms to be replaced by hierarchic
      mechanisms. These results have potential significance for the understanding of
      genotype-phenotype relationships in the evolution of metazoan form.

PMID- 11341678
TI  - Phenotypic and dynamical transitions in model genetic networks. II. Application
      to the evolution of segmentation mechanisms.
AB  - Knowledge of the genetic control of segmentation in Drosophila has made insect
      segmentation a paradigmatic case in the study of the evolution of developmental
      mechanisms. In Drosophila, the patterns of expression of segmentation genes are
      established simultaneously in all segments by a complex set of interactions
      between transcriptional factors that diffuse in a syncytium occupying the whole
      embryo. Such mechanisms cannot act in short germ-band insects where segments
      appear sequentially from a cellularized posterior proliferative zone. Here, we
      compare mechanisms of segmentation in different organisms and discuss how the
      transition between the different types of segmentation can be explained by small
      and progressive changes in the underlying gene networks. The recent discovery of
      a temporal oscillation in expression during somitogenesis of vertebrate homologs
      of the pair-rule gene hairy enhances the plausibility of an earlier proposal that
      the evolutionary origin of both the short- and long germ-band modes of
      segmentation was an oscillatory genetic network (Newman 1993). An implication of
      this scenario is that the self-organizing, pattern-forming system embodied in an
      oscillatory network operating in the context of a syncytium (i.e., a reaction
      diffusion system)-which is hypothesized to have originated the simultaneous mode
      of segmentation-must have been replaced by the genetic hierarchy seen in modern
      day Drosophila over the course of evolution. As demonstrated by the simulations
      in the accompanying article, the tendency for "emergent" genetic networks,
      associated with self-organizing processes, to be replaced through natural
      selection with hierarchical networks is discussed in relation to the evolution of
      segmentation.

PMID- 11341679
TI  - A novel thermostable xylanase from Thermomonospora sp.: influence of additives on
      thermostability.
AB  - An alkalothermophilic Thermomonospora sp. producing high levels of xylanase was
      isolated from self-heating compost. The culture produced 125 IU/ml of xylanase
      when grown in shake flasks at pH 9 and 50 degrees C for 96 h. The culture
      filtrate also contained cellulase (23 IU/ml), mannanase (1 IU/ml) and beta
      xylosidase (0.1 IU/ml) activities. The xylanase was active at a broad range of pH
      (5-9) and temperature (40-90 degrees C). The optimum pH and temperature were 7
      and 70 degrees C, respectively. The enzyme was stable in the pH range 5-8 and was
      thermostable with half-lives of 8 and 4 h at 60 degrees C and 70 degrees C,
      respectively, but only 9 min at 80 degrees C. The effects of a variety of
      compounds to enhance the stability of xylanase at 80 degrees C was studied.
      Addition of sorbitol, mannitol and glycerol increased the thermostability of
      xylanase in proportion to the number of hydroxyl groups per polyol molecule.
      Glycine also offered protection against thermoinactivation. Xylan, trehalose,
      gelatin and trehalose-gelatin mixture had marginal effect on the thermostability
      of xylanase at 80 degrees C.

PMID- 11341680
TI  - Utilisation of tomato pomace as a substrate for the production of vitamin B12--a
      preliminary appraisal.
AB  - The cellulose fraction in tomato pomace was hydrolysed using Trichoderma reesei,
      and the resultant sugars were fermented with Propionibacterium shermanii to
      produce vitamin B12. A multifactorial experiment revealed that aeration of the
      culture of T. reesei gave substantial improvements in cellulase activity as did
      higher concentrations of available nitrogen, but a rapid drop in pH appeared to
      inhibit extensive hydrolysis; after 14 days, the maximum level of cellulose
      degradation was only 34.4% of the total available, and the highest level of
      reducing sugars achieved was 15 g l(-1). When flasks with the latter
      concentration of reducing sugars were inoculated with P. shermanii, 11.1 mg l(-1)
      of B12 were produced under optimum conditions. If the degree of hydrolysis of the
      cellulose could be increased, then sufficient vitamin B12 might be generated to
      justify extraction but, even if purification does not prove to be economically
      feasible, a fermented tomato pomace (dried) with 50-55 mg kg(-1) or more of B12
      could prove a useful feedstuff for animals.

PMID- 11341681
TI  - Influence of the liquid-phase mass transfer on the performance of a packed-bed
      bioreactor for wastewater treatment.
AB  - This paper reports on the influence of the liquid-phase mass transfer on the
      performance of a horizontal-flow, anaerobic, immobilized-biomass (HAIB) reactor
      treating low-strength wastewater. The HAIB reactor was subjected to liquid
      superficial velocities (vs) ranging from 10 to 50 cm h(-1), corresponding to
      hydraulic detention time (theta h) of 10-2 h. The best performance was achieved
      at an overall theta h of 3.3 h due to the interdependence of biochemical
      reactions and mass transfer mechanisms for process optimization. The HAIB reactor
      was provided with four intermediate sampling ports, and the values of v(s) were
      fixed to permit sampling at different ports corresponding to thetah of 2 h as vs
      increased. The chemical oxygen demand removal (COD) efficiencies increased from
      68% to 82% with the increase of v(s) from 10 to 50 cm h(-1). It could be
      concluded that the performance of the HAIB reactor was improved significantly by
      increasing vs, thus decreasing the liquid-phase mass transfer resistance.

PMID- 11341682
TI  - Description of characteristics of humic substances from different waste
      materials.
AB  - Humic acids (HAs) extracted from different organic wastes have been characterised
      by chemical methods. The chemical properties of HAs showed differences depending
      on the source from which they were obtained. The C content in HAs from organic
      wastes (41.1-63.2%) fluctuated around the C value in soil HA with the exception
      of composted bark and tobacco dust. Compared with soil HA, the N contents of HAs
      from sewage sludge and brewery sludge were found much higher than the others.
      E4:E6 ratios for HAs in organic wastes were generally greater than that for soil
      HA, which indicated a low degree of condensation and humification. The carboxyl
      and phenolic-OH group contents ranged 0.51-2.23 and 11.1-20.7 meq g(-1),
      respectively. High values of carboxyl and phenolic-OH contents indicated that
      these materials were still within early stages of humification.

PMID- 11341683
TI  - Heavy metal removal in a biosorption column by immobilized M. rouxii biomass.
AB  - Mucor rouxii biomass was immobilized in a polysulfone matrix. The spherical
      immobilized biomass beads were packed in a column. The biosorption column was
      able to remove metal ions such as Pb, Cd, Ni and Zn not only from single
      component metal solutions but also from multi-component metal solutions. Column
      kinetics for metal removal were described by the Thomas model. For single
      component metal solutions, the metal removal capacities of the beads for Pb, Cd,
      Ni and Zn were 4.06, 3.76, 0.36 and 1.36 mg/g, respectively. For a multi
      component metal solution containing Cd, Ni and Zn, the capacities were 0.36, 0.31
      and 0.40 mg/g for Cd, Ni and Zn, respectively. The adsorbed metal ions were
      easily desorbed from the beads with 0.05N HNO3 solution. After acid desorption
      and regeneration with deionized water, the beads could be reused to adsorb metal
      ions at a comparable capacity.

PMID- 11341684
TI  - Allometry and biomass of Korean pine (Pinus koraiensis) in central Korea.
AB  - Aboveground tree biomass of Korean pine (Pinus koraiensis Sieb. et Zucc.) was
      determined for a natural forest of Korean pine and mixed deciduous trees and
      seven age classes of plantation forests in central Korea. Regression analyses of
      the dry weights of stem wood, stem bark, branches, and needles versus diameter at
      breast height were used to calculate regression equations of the form of log Y =
      a + b log X. Biomass of Korean pine in the mixed forest was 118 Mg ha(-1), and
      biomass in the plantations was linearly related to stand age, ranging from 52.3
      Mg ha(-1) in 11 to 20-year-old stands to 317.9 Mg ha(-1) in 71 to 80-year-old
      stands. The proportions of stem wood and stem bark in the total aboveground
      biomass decreased with stand age while those of branch and needle increased.
      Specific leaf area of Korean pine ranging from 35.2 to 52.1 cm2 g(-1) was
      significantly different among crown positions and needle ages; in general, lower
      crown position and current needles had the greatest surface area per unit dry
      weight.

PMID- 11341685
TI  - Characterisation of organic matter from anaerobic digestion of organic waste by
      aerobic microbial activity.
AB  - The aim of this study was to examine whether the characterisation of organic
      matter on the basis of an oxygen uptake rate (OUR) could be applied to organic
      waste from an anaerobic waste treatment process. Three anaerobic digestion
      experiments were carried out in a bioreactor. Volatile fatty acids (VFA) and
      dissolved organic carbon (DOC) were monitored. OUR-experiments were carried out
      with diluted samples from the process. The graphs of the OUR-experiments showed a
      clear lag-phase, which was due to the slow adaptation of aerobic microorganisms.
      Model simulations of the OUR versus time curve showed sufficient agreement, if
      based on one fraction of readily biodegradable and two fractions of less easily
      biodegradable organic matter. The shape of the simulated graphs was affected
      considerably by the value of the maintenance energy requirement rate qm and could
      be improved by reducing the standard value qm = 1 d(-1) to qm = 0.1 d(-1). Only
      little agreement was achieved when comparing the results of the OUR-experiments
      with the VFA- and DOC-concentrations. Experiments with additional trace elements
      and vitamins led to an increase in the OUR and proved that the oxygen consumption
      was not exclusively determined by the availability of organic matter.

PMID- 11341686
TI  - Production of a biopolymer flocculant from Bacillus licheniformis and its
      flocculation properties.
AB  - Bacillus licheniformis CCRC 12826 produced extracellularly an excellent
      biopolymer flocculant in a large amount when it was grown aerobically in a
      culture medium containing citric acid, glutamic acid and glycerol as carbon
      sources. The biopolymer flocculant was an extremely viscous material with a
      molecular weight over 2 x 10(6) by gel permeation chromatography. It could be
      easily purified from the culture medium by ethanol precipitation. It was shown to
      be a homopolymer of glutamic acid by amino acid analysis and thin layer
      chromatography and presumed to be poly-glutamic acid (PGA). This bioflocculant
      efficiently flocculated various organic and inorganic suspensions. It flocculated
      a suspended kaolin suspension without cations, although its flocculating activity
      was synergistically stimulated by the addition of bivalent or trivalent cations
      Ca2+, Fe3+ and Al3+. However, the synergistic effects of metal cations were most
      effective at neutral pH ranges. The comparison of the flocculating activity
      between the present biopolymer and a commercial lower molecular weight product
      showed that the biopolymer of the present study had much higher activity. The
      high productivity and versatile applications of PGA make its development as a new
      biodegradable, harmless, biopolymer flocculant economical and advantageous.

PMID- 11341687
TI  - Two-stage biohumus production from inedible potato biomass.
AB  - The feasibility of a two-stage bioconversion of inedible potato biomass into
      biohumus by oyster mushroom followed by worms was tested. As a raw material for
      biohumus production the inedible potato biomass in certain properties ranked
      below wheat straw. The most feasible method to convert the potato wastes into
      biohumus was to mix them with wheat straw at the mass ratio of 1:3 and then treat
      with mushrooms followed by worms. This gave a good yield of mushrooms. The
      biohumus produced from the mixture was suitable for use as a plant growth medium.

PMID- 11341688
TI  - Bioconversion of corn straw by coupling ensiling and solid-state fermentation.
AB  - A two-stage process that combined solid-state fermentation (SSF) and ensiling was
      used for bioconversion of corn straw, in order to increase nutritional value and
      palatability for animal feed. SSF of corn straw increased the level of protein
      from 6.7% to 14.7% and decreased the cellulose by 38.0% and hemicellulose by
      21.2%. Cellulase and xylanase were produced during SSF. After SSF, the fermented
      substrate was directly ensiled by inoculating with lactic acid bacteria (LAB). In
      situ produced enzymes and bacterial inoculation resulted in a rapid drop in pH, a
      high level of lactic acid production, partial degradation of cell wall components
      and generation of reducing sugars (RSs). Efficiency of ensiling at 25 degrees C,
      30 degrees C, 35 degrees C, 40 degrees C was evaluated. Temperature influenced
      the effect of ensiling; the higher the temperature, the shorter the ensiling
      period. The combined fermentation upgraded the nutritional value, enhanced the
      efficiency of ensiling and reduced bioprocessing costs.

PMID- 11341689
TI  - Hydrolysis of rice hull by crosslinked Aspergillus niger cellulase.
AB  - A. niger cellulase was crosslinked by glutaraldehyde to obtain a heat-stable
      enzyme preparation for rice hull cellulose hydrolysis. Under optimized
      crosslinking conditions of 0.12 M glutaraldehyde, pH 7.0, temperature 40 degrees
      C and at 45 min of crosslinking, a preparation having 15% more activity than free
      enzyme was obtained which also had considerable improvement in heat stability at
      65 degrees C and 70 degrees C. Whereas the free enzyme lost 80% of its activity
      in 4 h at 65 degrees C, the crosslinked preparation lost only 30% activity. The
      crosslinked preparation hydrolyzed cellulosic biomass more effectively giving 2.2
      mg/ml glucose and 52% corresponding saccharification in 4 h at 65 degrees C as
      compared to 14% saccharification by free enzyme under similar conditions.

PMID- 11341690
TI  - Regulation of cellulases and xylanases from a derepressed mutant of Cellulomonas
      flavigena growing on sugar-cane bagasse in continuous culture.
AB  - When the wild type Cellulomonas flavigena was grown on glycerol, xylose or
      cellobiose, it produced basal levels of carboxymethyl-cellulase (CMCase), filter
      paperase (FPase) and xylanase activities. By comparison, a catabolic derepressed
      mutant strain of the same organism produced markedly higher levels of these
      enzymes when grown on the same carbon sources. Sugar-cane bagasse induced both
      the wild type and the mutant strain to produce three- to eight-time higher levels
      of FPase and xylanase than was observed with xylose or cellobiose. Continuous
      culture was used to determine the minimal cellobiose or glucose concentrations
      that repress the enzyme synthesis in both strains. 2.5 g l(-1) glucose repressed
      FPase and xylanases from wild type, while 1.6 times more glucose was needed to
      repress the same activities in the PN-120 strain. In the same way, twofold more
      cellobiose was needed to reduce by 75% the CMCase and xylanase activities in the
      mutant compared to the wild type. The FPase in the presence of 4 g l(-1)
      cellobiose did not change in the same strain. Therefore, its derepressed and
      feedback resistant characters of PN-120 mutant are evident. On the other hand,
      isoelectrofocused crude extracts of mutant and wild strains induced by sugar-cane
      bagasse, did not show differences in protein patterns, however, the Schiffs
      staining was more intense in the PN-120 than in the wild strain. These results
      point out that the mutational treatment did not apparently change the
      extracellular proteins from mutant PN-120 and this could affect their regulation
      sites, since derepressed and feed-back resistant enzymes may be produced.

PMID- 11341691
TI  - Biological efficiency and nutritional value of Pleurotus ostreatus cultivated on
      spent beer grain.
AB  - Unpretreated spent beer grains were successfully used as a basic substrate
      material for the cultivation of Pleurotus ostreatus. The effects of spent grain
      types, additives, substrate moisture content, and substrate packing density on
      the yield and nutrition of fruit bodies were investigated. The cultivation
      results showed that few fruit bodies were formed on spent grain alone; however, a
      significantly high biological efficiency (19.1%) was obtained with the addition
      of wheat bran to (45%). The chemical analysis of fruit bodies indicated that P.
      ostreatus cultivated on spent grain substrate had a higher nutritional value than
      those grown on other reported types of substrates. The total amino acid content
      in the fruit bodies was 347.5 mg/g dry matter, and the crude protein content was
      as high as 53.3% on a dry weight basis. It was also found that the cultivation of
      P. ostreatus increased the crude protein content, while it decreased the ratio of
      lignin to cellulose, of the spent grain substrate.

PMID- 11341692
TI  - Nitrogen transformation during organic waste composting by the Rutgers system and
      its effects on pH, EC and maturity of the composting mixtures.
AB  - The evolution of the different forms of nitrogen during the composting of several
      wastes was studied, as well as its relation to the pH, electrical conductivity
      and parameters of maturity of the composts obtained. Four mixtures were prepared
      from different organic materials: sewage sludge, municipal solid waste, brewery
      sludge, sorghum bagasse, cotton waste and pine bark. The evolution of the
      different forms of nitrogen during composting depended on the material which
      supplied the nitrogen to the mixtures and the organic matter (OM) degradation
      rate during composting. The greatest concentration of ammonium was observed
      during the first weeks of composting, coinciding with the most intense period of
      OM degradation, and ammonium then decreased gradually to reach final values of
      below 0.04%. The use of urea as a nitrogen source in the mixtures led to high
      ammonium levels during the first weeks as a result of its rapid hydrolysis. The
      nitrification process began only when the temperature of the mixtures had dropped
      below 40 degrees C and its intensity depended on the quantity of ammonium present
      when the process began. The highest concentrations of NO3-N were always produced
      at the end of maturation, reaching values of 0.52%, 0.53%, 0.12% and 0.20% in the
      four mixtures studied. Nitrogen losses during composting depended on the
      materials used and on the pH values of the mixtures. Mixtures with the highest
      lignocellulose content showed the lowest losses (below 25%), while those
      containing municipal solid waste lost more than 40% of the initial content.
      Statistically significant correlations at a high probability level were found
      between the NO3-N concentration and pH and electrical conductivity. confirming
      that nitrification was responsible for the falling pH values and increasing
      electrical conductivity. The ratio of NH4-N and NO3-N concentrations was shown to
      be a clear indicator of the maturity of the mixtures during composting, the final
      values of 0.08, 0.04, 0,16 and 0.11 for the four mixtures being equal to, or
      below the maximum value established as a maturity index in other materials.

PMID- 11341693
TI  - Beneficial effects of Rhizopus oligosporus fermentation on reduction of
      glucosinolates, fibre and phytic acid in rapeseed (Brassica napus) meal.
AB  - Solid state fermentation was employed using Rhizopus oligosporus to develop a
      fermented product from rapeseed meal (RSM). The contents of glucosinolates,
      thiooxazolidones, phytic acid and crude fibre declined by 43.1%, 34%, 42.4% and
      25.5%, respectively, following inoculation with R. oligosporus. Fermentation also
      increased nitrogen and protein contents of the meal. This study may open a new
      prospective for a simple and cost effective technique for reduction of toxicants
      in RSM.

PMID- 11341694
TI  - Increased biogas production using microbial stimulants.
AB  - Laboratory studies were undertaken to evaluate the effect of microbial stimulants
      Aquasan and Teresan, on biogas yields from cattle dung and combined residues of
      cattle dung and kitchen waste, respectively. The addition of single dose of
      Aquasan at the rate of 10, 15 and 20 ppm to cattle dung on the first day of
      incubation resulted in increased gas yields ranging between 45.1 and 62.1 l/kg
      dry matter. Subsequent addition of Aquasan at 15 and 20 ppm dosage after a period
      of 15 days increased the gas yields by 15-16%. The gas production was found to be
      optimum at a dosage level of 15 ppm and was 39% and 55% higher with single and
      dual additions, respectively, than untreated cattle dung. In another bench scale
      study (1:1 dry matter) the addition of Teresan at 10 ppm concentration to the
      mixed residues of cattle dung and kitchen wastes at different solids
      concentration, produced 34.8% more gas (272.4 l/kg d.m.) than the uninoculated
      mixture at 15% TS concentration (202.4 l/kg d.m.).

PMID- 11341695
TI  - Mechanistic aspects of organophosphorothionate toxicity in fish and humans.
AB  - Metabolic transformation plays a major role in the mechanism of toxicity of
      organophosphorous (OP) pesticides. The modulation of their toxicity by oxonases
      and monooxygenases, alone or in combination, has been shown in mammals and fish.
      Very limited information exists for the identification of the metabolic factors
      relevant in the human toxicology of such chemicals. In this paper, we develop a
      simple algorithm, based on in vitro data, for the identification of fish species
      more susceptible to diazinon (D). Similar algorithms are likely to be applicable
      to other organophosphothionate (OPT) pesticides. We also report on preliminary
      studies on the OPT substrate specificity of human liver cytochromes P450 (CYPs):
      such information may be useful to understand the role of sulphoxidation in OPT
      toxicity to humans and to identify individuals with increased susceptibility to
      OPT toxicity. Studies of the mechanism of OPT toxicity may provide useful tools
      for a more detailed characterisation of these chemicals, with reference to the
      risk for the human population and to the impact on the fish species present in
      specific environments.

PMID- 11341696
TI  - Effects of atrazine and nicosulfuron on freshwater microalgae.
AB  - Growth modifications caused by various concentrations of atrazine and
      nicosulfuron were monitored in closed and continuous culture of Chlorella
      vulgaris (chlorophyta), Navicula accommoda (diatomophyta), and Oscillatoria
      limnetica (cyanophyta). The concentration at which algal growth rate was reduced
      twofold (EC50) was determined in the three species for both herbicides.
      Comparatively, the two toxicants were applied at 10 microg/l level in microcosms
      inoculated with natural phytoplankton from Lake Geneva. The relative abundances
      of major phytoplanktonic species were measured by algal cell count at the
      beginning and at the end of each experiment. Atrazine and nicosulfuron have
      different targets in plant metabolism, respectively, photosystem II (PSII) and
      acetolactate synthase (ALS), and the expected effects were different. Generally,
      the cultured phytoplankton exhibited various sensitivities, depending on species
      or herbicide. In the microcosms, the major taxa of natural phytoplanktonic
      samples exhibited various patterns, from acute toxicity to growth enhancement.
      For example, the diatoms inside the community were not affected by atrazine and
      nicosulfuron, except for Stephanodiscus minutulus that was sensitive to both, and
      Asterionella/formosa that was sensitive only to nicosulfuron. The specific
      physiology and the relationships among the phytoplanktonic communities have to be
      carefully considered when one would try to predict the extent of herbicide action
      on natural phytoplankton using in vitro tests. There is a need to test the toxic
      effect on various cultured strains, representative of most of the taxonomic
      composition of natural communities, to take into account the wide range of
      sensitivities and reaction to herbicide contamination. But this is not enough to
      give a solid frame when transposing the results to the field, and the use of more
      ecologically relevant systems is recommended.

PMID- 11341697
TI  - Effects of 2,4-dichlorophenoxy acetic acid dimethyl amine salt on dental hard
      tissue formation in rats.
AB  - 2,4-Dichlorophenoxy acetic acid dimethyl amine salt (2,4-D DMA), as one of the
      phenoxy acids, is used as a herbicide mainly against broad-leaf weeds in cereal
      crops, sugar cane, and on turf, pasture, and non-crop land. Some formulations of
      2,4-D may be contaminated with dioxins. Recently, it has been shown that
      chlorinated organic compounds, dioxins, and furans are present in mother's milk
      and may cause developmental defects in children's teeth. Therefore, we aimed to
      evaluate the effects of 2,4-D DMA on odontogenesis in rats. 2,4-D DMA was given
      orally combined with rat food to pregnant albino rats. Each group consisted of
      two pregnant rats and, 0 (control, group A), 25 ppm (group B), 50 ppm (group C),
      and 100 ppm (group D) 2,4-D DMA was given to each pregnant rat as daily intake.
      2,4-D DMA affected young rat's dental development and dose-related findings were
      found in experimental groups. The odontoblast layer was irregular and globular
      dentin formation was present in Groups B, C, and D but not in the control group.
      Thickness of enamel decreased in Groups C and D. The results of the study have
      shown that 2,4-D DMA could disturb dental development in rats even in relatively
      low doses. It is concluded that environmental contaminants such as chlorinated
      organic pesticides may play an important role in infant's dental development when
      taken via mother's milk.

PMID- 11341698
TI  - Differences between blood and liver aromatic DNA adduct formation.
AB  - Aromatic DNA adducts in the livers and blood of grey mullet (Mugil sp.) have been
      monitored between 1993 and 1996 by the isolation of DNA and the postlabeling of
      the DNA adducts with 32P. The grey mullet were sampled from three well
      characterised harbours, two in the northeastern Mediterranean and one in the
      northeastern Black Sea near Trabzon close to a site of aquaculture. One of the
      northeastern Mediterranean harbours was highly polluted with polynuclear aromatic
      hydrocarbons (PAHs) and was rich in inorganic nutrients. Larger grey mullet lived
      in this harbour than the other harbours and their livers possessed approximately
      100 aromatic DNA adducts per 10(8) nucleotides. The livers from grey mullet in
      the other two harbours possessed < or = 25 aromatic DNA adducts per 10(8)
      nucleotides but these concentrations depended on a variety of factors. Blood cell
      being regenerated more rapidly than liver cells, it is found that generally the
      ratio of DNA adduct concentrations in piscine liver and blood will increase with
      the pollution of the surrounding marine environment. Fishes are acceptable models
      for the metabolism of xenobiotics and the associated formation of harmful
      aromatic DNA adducts in organisms.

PMID- 11341699
TI  - Tissue distribution and temperature-dependence of Anguilla anguilla L. EROD
      activity following exposure to model inducers and relationship with plasma
      cortisol, lactate and glucose levels.
AB  - Anguilla anguilla L. ethoxyresorufin-O-deethylase (EROD) elevation by 2.7 microM
      beta-naphthoflavone (BNF) 3 days water exposure, or 4 mg/kg ip exposure, was
      studied in four different organs--liver, kidney, gills, and intestine. The
      results demonstrated a significant increase in liver EROD activity for the two
      previous conditions, whereas kidney EROD activity only increased during the
      intraperitoneal exposure. A. anguilla was also exposed during 8, 16, and 24 h to
      water contaminated with 2.7 microM BNF or benzo[a]pyrene (BaP) at 20 degrees C
      and 25 degrees C. Both compounds significantly increased liver EROD activity from
      8 up to 24 h. There was no significant difference in liver EROD activity
      elevation by both compounds, either at 20 degrees C or 25 degrees C. Liver EROD
      activity was demonstrated to be one of the first warning systems concerning the
      presence of polycyclic aromatic hydrocarbons (PAHs) in water. A. anguilla 3 h
      exposure to diesel oil water-soluble fraction (DWSF) significantly increased
      plasma cortisol and significantly decreased plasma lactate. A prolonged exposure
      beyond 3 h, i.e. 4 h, 2, 3, 4, and 6 days to the previous conditions demonstrated
      a significant liver EROD activity elevation from Day 2 up to 6, and a significant
      increase in erythrocytic nuclear abnormalities (ENA) at Day 6.

PMID- 11341700
TI  - Towards a clean Izmit Bay.
AB  - The elongated semi-enclosed Bay of Izmit, which receives both domestic and
      industrial wastes, has been monitored by measuring its physical and biochemical
      parameters for 2 years, 1994-1995. It is clear that there are two distinct water
      masses. The upper layer has been occupied by the less saline (22-26 ppt) waters
      of the Black Sea origin; whereas the lower layer contains saline (38.5 ppt)
      Mediterranean waters. The seasonal variations in the biochemical characteristics
      were dependent on the bay's two-layer flow system. If one considers the
      distribution of transparency in the upper bay waters, it has been observed that
      the Secchi disk depth (SDD) decreases from west to east. Furthermore, these
      depths are limited by the high primary productivity associated with the low
      concentrations of nutrients observed during the spring. Discharges of wastes into
      the surface waters significantly affect the biological production and oxygen
      consumption in the lower layer. Within the last 10 years, 80% of organic matter
      has been removed from industrial wastewater. However, organic loads from the
      domestic wastewaters have doubled because of the growth in the surrounding
      population. Fortunately, as a result, the total organic loads in the bay have not
      changed significantly within the last 10 years.

PMID- 11341701
TI  - The pollution status and the toxicity of surface sediments in Izmit Bay (Marmara
      Sea), Turkey.
AB  - Izmit Bay is one of the most polluted and populated enclosed sea in Turkey. It
      has been the centre of industrial activities for the last 30 years. Seven major
      sources enter the bay waters along the north coastline of the bay. This
      investigation forms part of continuing ecotoxicology studies in the Izmit Bay
      designed to constrain and minimise the pollution caused by flourishing industry
      and a growing population. Sediments sampled from the mouths of the major
      discharges of Izmit Bay were analysed for their organic carbon, total polycyclic
      aromatic hydrocarbon (t-PAH) and trace inorganic element (Cd, Al, As, Pb, Hg and
      Cu) contents and compared with those found in the sediments from the reference
      station in the outer bay (in the Marmara Sea). The toxicity of sediments was
      determined in the bulk and elutriate samples by using algal (Phaeodactylum
      tricornutum) batch bioassays. Chemical data showed that the sediments collected
      from the inner sites of the bay have been contaminated with Cd, Hg, As and PAHs.
      Organic carbon contents were also found higher. All the major industrial
      discharges into the bay are now biologically treated but bioassays performed with
      bulk sediments revealed that the recent sediments are toxic to the microalgae
      throughout the bay. The results are consistent with the previous toxicity studies
      performed with the industrial discharges.

PMID- 11341702
TI  - Distributions of heavy metals in the surface sediments of the Gulf of Saros, NE
      Aegean Sea.
AB  - The Gulf of Saros in the northeastern Aegean Sea (Turkey) is a relatively
      unpolluted marine environment. There is almost no industry and only small
      settlements in the surrounding region. The main sources of fresh water and
      sediment to the Gulf are the Meric River in the northwest and the Kavak Creek in
      the east. It has an asymmetric bathymetry with a 10-km-wide shelf to the north
      and up to 15-km-wide, 700-m-deep trough in the south. Water circulation in the
      Gulf is characterized by longshore currents and anticyclonic eddies. The Black
      Sea waters, leaving the Sea of Marmara through the Canakkale Strait, are known to
      enter the southern Gulf during the summer. The surface sediments on the northern
      shelf consist mainly of sand, whereas those on the slope and the deep trough are
      mainly silt and clay. The ranges of Fe, Mn, Cu, Zn, Pb, Ni, and Hg contents of
      the surface sediments from the Gulf of Saros are 0.25 4.60%, 114 1740 ppm, 6-44
      ppm, 23-154 ppm, 2-80 ppm, 14-145 ppm, and 10-130 ppb, respectively. These values
      are low compared to those from the other neighboring marine environments,
      indicating the pristine nature of the Gulf in terms of metal pollution. However,
      most metal and organic carbon (Corg) distributions in the Gulf sediments show the
      effect of anthropogenic and natural inputs to the northwestern and eastern shelf
      areas from the Meric River and the Kavak Creek and to the deep trough from the
      Black Sea waters.

PMID- 11341703
TI  - Long-term abundance dynamics of coastal zooplankton in the Gulf of Riga.
AB  - The dynamics of three most abundant mesozooplankton species in the coastal zone
      of the Gulf of Riga--Bosmina longispina, Synchaeta baltica, Keratella quadrata-
      is analyzed to detect the regulating environmental factors. The only significant
      downward trend of species abundance was found for S. baltica in autumn.
      Statistically significant correlation was estimated only between the summer
      salinity and the abundance of B. longispina. K. quadrata though showed a negative
      correlation with summer salinity. The abundance of S. baltica had only
      nonsignificant correlations with the environmental factors. The abundance of
      coastal mesozooplankton species is determined by the combination of hydrological
      regime, predation pressure, benthic conditions and the success of living
      strategy. The change of fresh- and saline water masses at the coastal areas
      supplies sufficient food amount but can cause decline in hatching abilities.

PMID- 11341704
TI  - Migration ability of radionuclides in soil-vegetation cover of Belarus after
      Chernobyl accident.
AB  - This article illustrates the experimental experience achieved in the research of
      the self-restoration of radioactive-contaminated natural ecosystems. The main
      directions of studies were: the content and geochemical stability of "hot"
      particles in radioactive fallout from Chernobyl accident; the physicochemical
      forms (water-soluble, exchangeable, mobile and fixed) of Cs-137, Sr-90, Pu-239,
      240 and Am-241 in the wide varieties of soils; the biological accessibility of
      radionuclides and their contents in soil pore solutions; and the dynamics and
      migration parameters of radionuclides vertical redistribution in different
      landscape conditions.

PMID- 11341705
TI  - Treatment of wastewater by natural systems.
AB  - Experimental results from a pilot-scale constructed wetland (CW) treatment plant
      have been described. The study was conducted at two different systems: continuous
      and batch. In the continuous system, the treatment yields were monitored in
      different loading conditions in 1-year period. The pilot plant consists of two
      serially connected tanks settled up with fillers; Cyperus was used as treatment
      media and wastewater between the two tanks was recycled periodically. Chemical
      oxygen demand (COD) and suspended solid (SS) removal efficiencies were obtained
      as 90% and 95%, respectively. The effluent COD concentration at an average
      loading of 122 g COD/m2 day was satisfactory for the Turkish Water Pollution
      Control Regulation. This means that a 0.8 m2 of garden area per person is
      required. Other removal values for the same conditions were as follows: total
      Kjeldahl nitrogen (TKN) was 77%, total nitrogen (TN) was 61%, and PO4(3-) -P was
      39%. The batch experimental systems consist of 12 pairs of serially connected
      tanks, with each pair having a surface area of 1 m2. Each set was filled with
      sewage once a day, and the wastewater between the paired tanks was recycled
      periodically by the pump. Each pair of tanks was filled with materials such as
      gravel, peat, and perlite. Seven of them were vegetated with Phragmites, Cyperus,
      Rush, Iris, Lolium, Canna, and Paspalum, while the other five were not seeded.
      The best performances were obtained by Iris for COD (% 94), by Canna for ammonia
      nitrogen (% 98), and by Iris for total nitrogen (% 90) and phosphorus (% 55)
      removal.

PMID- 11341706
TI  - Three-dimensional Bayesian optical image reconstruction with domain
      decomposition.
AB  - Most current efforts in near-infrared optical tomography are effectively limited
      to two-dimensional reconstructions due to the computationally intensive nature of
      full three-dimensional (3-D) data inversion. Previously, we described a new
      computationally efficient and statistically powerful inversion method APPRIZE
      (automatic progressive parameter-reducing inverse zonation and estimation). The
      APPRIZE method computes minimum-variance estimates of parameter values (here,
      spatially variant absorption due to a fluorescent contrast agent) and covariance,
      while simultaneously estimating the number of parameters needed as well as the
      size, shape, and location of the spatial regions that correspond to those
      parameters. Estimates of measurement and model error are explicitly incorporated
      into the procedure and implicitly regularize the inversion in a physically based
      manner. The optimal estimation of parameters is bounds-constrained, precluding
      infeasible values. In this paper, the APPRIZE method for optical imaging is
      extended for application to arbitrarily large 3-D domains through the use of
      domain decomposition. The effect of subdomain size on the performance of the
      method is examined by assessing the sensitivity for identifying 112 randomly
      located single-voxel heterogeneities in 58 3-D domains. Also investigated are the
      effects of unmodeled heterogeneity in background optical properties. The method
      is tested on simulated frequency-domain photon migration measurements at 100 MHz
      in order to recover absorption maps owing to fluorescent contrast agent. This
      study provides a new approach for computationally tractable 3-D optical
      tomography.

PMID- 11341707
TI  - Noninvasive estimation of the aorta input function for measurement of tumor blood
      flow with.
AB  - Quantitative measurement of tumor blood flow with [15O]water can be used to
      evaluate the effects of tumor treatment over time. Since quantitative flow
      measurements require an input function, we developed the profile fitting method
      (PFM) to measure the input function from positron emission tomography images of
      the aorta. First, a [11C]CO scan was acquired and the aorta region was analyzed.
      The aorta diameter was determined by fitting the image data with a model that
      includes scanner resolution, the measured venous blood radioactivity
      concentration, and the spillover of counts from the background. The diameter was
      used in subsequent fitting of [15O]water dynamic images to estimate the aorta and
      background radioactivity concentrations. Phantom experiments were performed to
      test the model. Image quantification biases (up to 15%) were found for small
      objects, particularly for those in a large elliptical phantom. However, the bias
      in the PFM concentration estimates was much smaller (2%-6%). A simulation study
      showed that PFM had less bias and/or variability in flow parameter estimates than
      an ROI method. PFM was applied to human [11C]CO and [15O]water dynamic studies
      with left ventricle input functions used as the gold standard. PFM parameter
      estimates had higher variability than found in the simulation but with minimal
      bias. These studies suggest that PFM is a promising technique for the noninvasive
      measurement of the aorta [15O]water input function.

PMID- 11341708
TI  - Robust midsagittal plane extraction from normal and pathological 3-D
      neuroradiology images.
AB  - This paper focuses on extracting the ideal midsagittal plane (iMSP) from three
      dimensional (3-D) normal and pathological neuroimages. The main challenges in
      this work are the structural asymmetry that may exist in pathological brains, and
      the anisotropic, unevenly sampled image data that is common in clinical practice.
      We present an edge-based, cross-correlation approach that decomposes the plane
      fitting problem into discovery of two-dimensional symmetry axes on each slice,
      followed by a robust estimation of plane parameters. The algorithm's tolerance to
      brain asymmetries, input image offsets and image noise is quantitatively
      evaluated. We find that the algorithm can extract the iMSP from input 3-D images
      with 1) large asymmetrical lesions; 2) arbitrary initial rotation offsets; 3) low
      signal-to-noise ratio or high bias field. The iMSP algorithm is compared with an
      approach based on maximization of mutual information registration, and is found
      to exhibit superior performance under adverse conditions. Finally, no
      statistically significant difference is found between the midsagittal plane
      computed by the iMSP algorithm and that estimated by two trained
      neuroradiologists.

PMID- 11341709
TI  - Elastic registration of fMRI data using Bezier-spline transformations.
AB  - A three-dimensional (3-D) elastic registration algorithm has been developed to
      find a veridical transformation that maps activation patterns from functional
      magnetic resonance imaging (fMRI) experiments onto a 3-D high-resolution
      anatomical dataset. The proposed algorithm uses trilinear Bezier-splines and a 3
      D voxel-based optimization technique to determine the transformation that maps
      the functional data onto the coordinate system of the anatomical dataset. Simple
      conditions are presented which guarantee that the data are mapped one-to-one on
      each other. Two voxel-based similarity measures, the linear correlation
      coefficient and the entropy correlation coefficient, are used. Their performance
      with respect to the registration of fMRI data is compared. Tests on simulated and
      real data have been performed to evaluate the accuracy of the method. Our results
      demonstrate that subvoxel accuracy can be achieved even for noisy low-resolution
      multislice datasets with local distortions up to 10 mm. Although the method is
      optimized for the registration of functional and anatomical MR images, it can
      also be used for solving other elastic registration problems.

PMID- 11341710
TI  - A rapid look-up table method for reconstructing MR images from arbitrary K-space
      trajectories.
AB  - Look-up tables (LUTs) are a common method for increasing the speed of many
      algorithms. Their use can be extended to the reconstruction of nonuniformly
      sampled k-space data using either a discrete Fourier transform (DFT) algorithm or
      a convolution-based gridding algorithm. A table for the DFT would be
      precalculated arrays of weights describing how each data point affects all of
      image space. A table for a convolution-based gridding operation would be a
      precalculated table of weights describing how each data point affects a small k
      space neighborhood. These LUT methods were implemented in C++ on a modest
      personal computer system; they allowed a radial k-space acquisition sequence,
      consisting of 180 views of 256 points each, to be gridded in 36.2 ms, or, in
      approximately 800 ns/point. By comparison, a similar implementation of the
      gridding operation, without LUTs, required 45 times longer (1639.2 ms) to grid
      the same data. This was possible even while using a 4 x 4 Kaiser-Bessel
      convolution kernel, which is larger than typically used. These table-based
      computations will allow real time reconstruction in the future and can currently
      be run concurrently with the acquisition allowing for completely real-time
      gridding.

PMID- 11341711
TI  - An EM algorithm for estimating SPECT emission and transmission parameters from
      emissions data only.
AB  - A maximum-likelihood (ML) expectation-maximization (EM) algorithm (called EM
      IntraSPECT) is presented for simultaneously estimating single photon emission
      computed tomography (SPECT) emission and attenuation parameters from emission
      data alone. The algorithm uses the activity within the patient as transmission
      tomography sources, with which attenuation coefficients can be estimated. For
      this initial study, EM-IntraSPECT was tested on computer-simulated attenuation
      and emission maps representing a simplified human thorax as well as on SPECT data
      obtained from a physical phantom. Two evaluations were performed. First, to
      corroborate the idea of reconstructing attenuation parameters from emission data,
      attenuation parameters (mu) were estimated with the emission intensities (lambda)
      fixed at their true values. Accurate reconstructions of attenuation parameters
      were obtained. Second, emission parameters lambda and attenuation parameters mu
      were simultaneously estimated from the emission data alone. In this case there
      was crosstalk between estimates of lambda and mu and final estimates of lambda
      and mu depended on initial values. Estimates degraded significantly as the
      support extended out farther from the body, and an explanation for this is
      proposed. In the EM-IntraSPECT reconstructed attenuation images, the lungs,
      spine, and soft tissue were readily distinguished and had approximately correct
      shapes and sizes. As compared with standard EM reconstruction assuming a fix
      uniform attenuation map, EM-IntraSPECT provided more uniform estimates of cardiac
      activity in the physical phantom study and in the simulation study with tight
      support, but less uniform estimates with a broad support. The new EM algorithm
      derived here has additional applications, including reconstructing emission and
      transmission projection data under a unified statistical model.

PMID- 11341712
TI  - Automated melanoma recognition.
AB  - A system for the computerized analysis of images obtained from ELM has been
      developed to enhance the early recognition of malignant melanoma. As an initial
      step, the binary mask of the skin lesion is determined by several basic
      segmentation algorithms together with a fusion strategy. A set of features
      containing shape and radiometric features as well as local and global parameters
      is calculated to describe the malignancy of a lesion. Significant features are
      then selected from this set by application of statistical feature subset
      selection methods. The final kNN classification delivers a sensitivity of 87%
      with a specificity of 92%.

PMID- 11341713
TI  - Comparison of low-contrast detail perception on storage phosphor radiographs and
      digital flat panel detector images.
AB  - A contrast detail analysis was performed to compare perception of low-contrast
      details on X-ray images derived from digital storage phosphor radiography and
      from a flat panel detector system based on a cesium iodide/amorphous silicon
      matrix. The CDRAD 2.0 phantom was used to perform a comparative contrast detail
      analysis of a clinical storage phosphor radiography system and an indirect type
      digital flat panel detector unit. Images were acquired at exposure levels
      comparable to film speeds of 50/100/200/400 and 800. Four observers evaluated a
      total of 50 films with respect to the threshold contrast for each detail size.
      The numbers of correctly identified objects were determined for all image
      subsets. The overall results show that low-contrast detail perception with
      digital flat panel detector images is better than with state of the art storage
      phosphor screens. This is especially true for the low-exposure setting, where a
      nearly 10% higher correct observation ratio is reached. Given its high detective
      quantum efficiency the digital flat panel technology based on the cesium iodide
      scintillator/amorphous silicon matrix is best suited for detection of low
      contrast detail structures, which shows its high potential for clinical imaging.

PMID- 11341714
TI  - Permutation testing made practical for functional magnetic resonance image
      analysis.
AB  - We describe an efficient algorithm for the step-down permutation test, applied to
      the analysis of functional magnetic resonance images. The algorithm's time bound
      is nearly linear, making it feasible as an interactive tool. Results of the
      permutation test algorithm applied to data from a cognitive activation paradigm
      are compared with those of a standard parametric test corrected for multiple
      comparisons. The permutation test identifies more weakly activated voxels than
      the parametric test, always activates a superset of the voxels activated by this
      parametric method, almost always yields significance levels greater than or equal
      to those produced by the parametric method, and tends to enlarge activated
      clusters rather than adding isolated voxels. Our implementation of the
      permutation test is freely available as part of a widely distributed software
      package for analysis of functional brain images.

PMID- 11341715
TI  - State of the journal: 2001.

PMID- 11341716
TI  - Maternal perceptions of pediatric providers for children with chronic illnesses.
AB  - OBJECTIVE: To identify maternal perceptions of general and subspecialty pediatric
      providers of children with selected chronic illnesses. METHOD: Cross-sectional
      analyses of survey data. Sample was recruited from eight specialty and four
      general pediatric practices in an urban setting. Interviews were conducted with
      mothers of 159 children with one of four chronic illnesses: sickle cell anemia,
      cystic fibrosis, diabetes, and moderate/severe asthma. About 56% of the
      participants were white; 40% were African-American; 11% were receiving public
      assistance. The main outcome measures were maternal reports of which pediatric
      providers: are visited in the past year, are seen most frequently, have been seen
      over the longest period of time, relied on most, and know their family best.
      Rates of dissatisfaction with these providers are also reported. RESULTS:
      Overall, more mothers reported that they relied on their general pediatric
      providers, saw them more frequently, and had longer relationships with them than
      their subspecialty pediatric providers. However, mothers were more satisfied with
      the care they received from their subspecialty providers than from their primary
      care providers. CONCLUSIONS: Our findings illustrate the complexity of maternal
      perceptions of the different roles that general and subspecialty pediatric
      providers play in the care of children with chronic illness.

PMID- 11341717
TI  - Prenatal care utilization among non-Hispanic Whites, African Americans, and
      Mexican Americans.
AB  - OBJECTIVES: The general objective of this study is to explain differentials in
      prenatal care (PNC) utilization in a nationally representative sample of non
      Hispanic White (Anglo), African American, and Mexican American women. METHOD: The
      analysis is based on the National Maternal and Infant Health Survey.
      Multivariate, multinomial logistic regression models were employed to adjust for
      demographic, socioeconomic, medical risk, and program participation factors, as
      well as for perceived barriers. Both race/ethnic-specific models and models with
      race/ethnicity as a covariate were estimated. RESULTS: Inadequate PNC use was
      much less common among Anglos (10.4%) as compared to African Americans and
      Mexican Americans (22.1% and 25.0%, respectively). In fully adjusted models, the
      odds ratio (OR) of African Americans receiving inadequate PNC was 1.46, while the
      risk for Mexican Americans was greater (OR = 1.93). Perception of obstacles to
      PNC access doubled the odds of receiving inadequate care, but this psychosocial
      variable had little impact on race/ethnic differentials. Race/ethnic-specific
      models uncovered potentially important racial/ethnic variations associated with
      perception of barriers, marital status, and program participation. CONCLUSIONS:
      Although the same risk factors sometimes have different effects across
      race/ethnic groups, and while certain findings indicate a beneficial impact of
      health outreach efforts and program participation, our findings support the
      conclusion that PNC utilization continues to be stratified along race/ethnic
      lines.

PMID- 11341718
TI  - The impact of national health insurance on the utilization of health care
      services by pregnant women: the case in Taiwan.
AB  - OBJECTIVES: Substantially increased funding for health care services occurred in
      Taiwan after the implementation of a national health insurance plan in 1995. This
      study attempts to examine the impact of this national health insurance plan on
      the utilization of prenatal and intrapartum care services. METHODS: Nationally
      representative surveys of all pregnant women in Taiwan in 1989 (1,662
      participants) and in 1996 (3,626 participants) were included in the analysis. We
      first compared the distribution of birth characteristics between the two surveys.
      We then calculated the rate of utilization of various prenatal and intrapartum
      care services in the two surveys in the overall sample and in subsamples,
      stratified by maternal education, age, and parity. RESULTS: The utilization of
      most prenatal and intrapartum care services, especially the complicated
      laboratory tests, increased in 1996 compared to 1989. For example, the proportion
      of women who received amniocentesis increased from 1.62% in 1989 to 5.60% in 1996
      and German measles testing increased from 5.96% to 27.11%. By contrast, the
      proportion of women who received consultation services was stable over time, or
      for family planning, consultation declined from 33.21% to 27.00%. These changes
      in utilization over time were consistently observed across different maternal
      education, age, and parity groups. CONCLUSIONS: The utilization of prenatal and
      intrapartum care services, especially for the more expensive services, has
      substantially increased in Taiwan since the implementation of the national health
      insurance. For countries considering similar national health insurance plan, it
      may be helpful to consider cost-containing measures before the implementation of
      such a plan.

PMID- 11341719
TI  - Children's access to dental care in Connecticut's Medicaid managed care program.
AB  - OBJECTIVE: To describe dental care utilization and access problems in
      Connecticut's Medicaid managed care program, using quantitative and qualitative
      research methods. METHODS: Using Medicaid managed care enrollment and encounter
      data from Connecticut, utilization rates for preventive care and treatment
      services are determined for 87,181 children who were continuously enrolled in
      Medicaid managed care for 1 year in 1996-97. Sociodemographic and enrollment
      factors associated with utilization are identified using bivariate and
      multivariate methods. Dental providers and practices where children received
      services are described. Qualitative methods are used to characterize problems
      experienced by families seeking dental care during the study period. RESULTS:
      Only 30.5% of children continuously enrolled in Medicaid managed care for 1 year
      received any preventive dental services; 17.8% received any treatment services.
      Children who received preventive care were eight times more likely to have
      received treatment services. Utilization was higher among (a) younger children,
      (b) children who lived in Hartford and in other counties served by public dental
      clinics, and (c) children enrolled in health plans that did not subcontract for
      administration of dental services. Just 5% of providers, primarily those in
      public dental clinics, performed 50% of the services. Families whose children
      needed care encountered significant administrative and logistical problems when
      trying to find willing providers and obtain appointments. CONCLUSIONS: Access to
      dental care is a problem for children in Connecticut's Medicaid managed care
      program. Several features of managed care have negatively affected access. Public
      dental clinics served many children across the state and contributed to higher
      utilization of preventive care and treatment services among children living in
      Hartford.

PMID- 11341720
TI  - The MCH Certificate Program: a new path to graduate education in public health.
AB  - OBJECTIVE: The purpose of the MCH Certificate Program was threefold: to develop a
      new educational initiative in response to national and local demands for
      increased MCH workforce capacity, to eliminate key financial and nonfinancial
      barriers to advanced MCH academic preparation, and to improve rates of
      recruitment and retention of students from minority communities, thus enhancing
      the quality of MCH services available to the region. METHODS: An MCH Certificate
      Program, designed for clinicians (e.g., nurses, occupational therapists and
      nutritionists) and public health practitioners as a bridge to graduate programs
      in public health, combined a competency based curriculum with skills workshops,
      leadership seminars, mentoring, small group activities, and an interactive
      teaching format. RESULSTS: Students from the first two cohorts (n = 45) report an
      expansion of core public health knowledge (issues, policies, and strategies),
      enhanced self-confidence, and efficacy. Half have experienced job changes that
      represent increased responsibility, leadership, and professional advancement. A
      third are enrolled in or have completed a formal program of graduate study in
      MCH. CONCLUSIONS: This innovative MCH Certificate Program, now in its fourth
      year, is a new approach to increasing workforce capacity and a successful model
      of instruction for adult learners. It has the potential for adaptation to a
      variety of educational settings and MCH populations, and helps to expand the
      continuum of MCH training experiences in schools of public health.

PMID- 11341721
TI  - Recognition of a new field: the National MCH Epidemiology Awards.

PMID- 11341722
TI  - Predictors of pregnancy-associated change in physical activity in a rural white
      population.
AB  - OBJECTIVE: The objective of this study was to examine the relationship of
      sociodemographic and psychosocial characteristics and exercise prior to pregnancy
      to change in physical activity (PA) during pregnancy. METHODS: This study was
      part of the Bassett Mothers' Health Project (BMHP), a prospective cohort study of
      women who enrolled for prenatal care in the Bassett Healthcare system between
      November 7, 1994, and November 15, 1996. Six hundred twenty-two women met the
      eligibility criteria and were enrolled in the study. Sociodemographic and
      psychosocial characteristics and exercise behavior were assessed prenatally using
      the medical record and an anonymous mailed questionnaire. Staged linear
      regression analysis was used to predict change in physical activity with the
      psychosocial and sociodemographic characteristics as the independent variables
      and prepregnancy exercise frequency as a control variable. RESULTS: Women who
      were older, more educated, and had higher household incomes were more likely to
      exercise prior to pregnancy (p < .05). Change in PA after becoming pregnant was
      associated with prepregnancy exercise frequency (p < .001). Women who exercised
      frequently moderated their activity, while sedentary women maintained or
      increased their PA after becoming pregnant. Exercise self-efficacy (the belief in
      one's ability to exercise regularly) and body mass index (BMI) were positive
      predictors of change in PA (p < .05), while prepregnancy exercise frequency
      remained significant as a control variable. CONCLUSION: Interventions that aim to
      help women maintain or increase their PA during the perinatal period should be
      designed to increase exercise self-efficacy.

PMID- 11341723
TI  - Construction of a framework map in Pinus contorta subsp. latifolia using random
      amplified polymorphic DNA markers.
AB  - We report on the construction of the first random amplified polymorphic DNA
      (RAPD) framework map in Pinus contorta subsp. latifolia. Genomic DNA of haploid
      megagametophytes from 90 open-pollinated seeds originating from a single tree
      were amplified with 840 random decamer oligonucleotide primers by the polymerase
      chain reaction. Three-hundred twenty-eight RAPD markers with fragment sizes that
      ranged between 260 and 3080 base pairs were found segregating at 110 random
      decamer oligonucleotide primers. Of these 328 RAPD markers, 148 were mapped to 16
      framework linkage groups and 77 were mapped as accessory markers onto the
      framework linkage groups, on a support interval of minimal LOD score of 3. The 16
      framework maps cover a distance of 2287 cM. The estimate of genome size was 2407
      cM with a 95% confidence interval of 2304-2459 cM.

PMID- 11341724
TI  - Melon bacterial artificial chromosome (BAC) library construction using improved
      methods and identification of clones linked to the locus conferring resistance to
      melon Fusarium wilt (Fom-2).
AB  - Utilizing improved methods, two bacterial artificial chromosome (BAC) libraries
      were constructed for the multidisease-resistant line of melon MR-1. The HindIII
      library consists of 177 microtiter plates in a 384-well format, while the EcoRI
      library consists of 222 microtiter plates. Approximately 95.6% of the HindIII
      library clones contain nuclear DNA inserts with an average size of 118 kb,
      providing a coverage of 15.4 genome equivalents. Similarly, 96% of the EcoRI
      library clones contain nuclear DNA inserts with an average size of 114 kb,
      providing a coverage of 18.7 genome equivalents. Both libraries were evaluated
      for contamination with high-copy vector, empty pIndigoBac536 vector, and
      organellar DNA sequences. High-density filters were screened with two genetic
      markers FM and AM that co-segregate with Fom-2, a gene conferring resistance to
      races 0 and 1 of Fusarium wilt. Fourteen and 18 candidate BAC clones were
      identified for the FM and AM probes, respectively, from the HindIII library,
      while 34 were identified for the AM probe from filters A, B, and C of the EcoRI
      library.

PMID- 11341725
TI  - Dynamic microsatellites in transcribed regions of gastropod mitochondrial 16S
      rDNA.
AB  - Length variations of repetitive sequences in different AT-rich loop-coding
      regions of mitochondrial 16S rDNA in two gastropod species were discovered during
      intraspecific haplotype surveys. Examination of the discrete length variation of
      the basic repeat unit in a phylogenetic framework led to the conclusion of a
      microsatellite-like mutational dynamic. The observations suggest that the
      presence of a repetitive sequence structure alone is sufficient to trigger this
      dynamic.

PMID- 11341726
TI  - Characterization of an opsin gene from the ascomycete Leptosphaeria maculans.
AB  - An opsin gene (ops) has been characterized from Leptosphaeria maculans, the
      ascomycete that causes black-leg disease of Brassica species. This is the second
      opsin identified outside the archaeal and animal kingdoms. The gene encodes a
      predicted protein with high similarity (70.3%) and identity (53.3%) to the nop-1
      opsin of another ascomycete Neurospora crassa. The L. maculans opsin also has
      identical amino acid residues in 20 of the 22 residues in the retinal-binding
      pocket of archaeal opsins. Opsin, on the fourth largest chromosome of L. maculans
      and 22 cM from the mating type locus, is the first cloned gene to be mapped in L.
      maculans. Opsin is transcribed at high levels in mycelia grown in the presence
      and absence of light; this pattern is in contrast with that of the N. crassa
      opsin, which is transcribed only in the light.

PMID- 11341727
TI  - Chromosomal principle of radiation-induced F1 sterility in Ephestia kuehniella
      (Lepidoptera: Pyralidae).
AB  - A dose-response analysis of chromosomal aberrations was performed in male progeny
      of gamma-irradiated males in the flour moth, Ephestia kuehniella. For comparison,
      several female progeny from each dose level were examined. Aberrations were
      detected on microspread preparations of pachytene nuclei in the electron
      microscope and classified according to pairing configurations of synaptonemal
      complexes (SCs). Fragmentation and various translocations were the most numerous
      aberrations, whereas interstitial deletion and inversion were rare. At 100 Gy,
      relatively simple multiple translocations were found. Multiple translocations
      showing complicated configurations occurred at 150 and 200 Gy, and their number
      increased with the dose. In males, the mean number of chromosomal breaks
      resulting in aberrations linearly increased with the dose from 8.4 to 16.2 per
      nucleus. In females, this value achieved a maximum of 11.2 breaks/nucleus at 200
      Gy. Three factors were suggested to contribute to the reported higher level of F1
      sterility in males than females: (i) survival of males with high numbers of
      breaks, (ii) crossing-over in spermatogenesis but not in the achiasmatic
      oogenesis, and (iii) a higher impact of induced changes on the fertility of males
      than females. It was concluded that translocations are most responsible for the
      production of unbalanced gametes resulting in sterility of F1 moths. However, F1
      sterility predicted according to the observed frequency of aberrations was much
      higher than the actual sterility reported earlier. This suggests a regulation
      factor which corrects the predicted unbalanced state towards balanced segregation
      of translocated chromosomes.

PMID- 11341728
TI  - Inheritance of microsatellite loci in the polyploid lake sturgeon (Acipenser
      fulvescens).
AB  - Inheritance in the expression of amplicons for four microsatellite primer pairs
      was determined using 10 families created from gametes of wild lake sturgeon
      (Acipenser fulvescens). Loci Afu34 and Afu68 expressed a maximum of two even
      intensity bands per individual and had progeny genotype ratios that fit disomic
      inheritance (P > 0.05). Some variation exhibited at Afu34 and Afu68 was
      attributable to a null allele. Genotype expression at both loci also indicated
      that one female parent had transmitted unreduced gametes. Primer Afu39 amplified
      products that exhibited four gene doses, where genotype counts fit expected
      ratios for disomic inheritance (P > 0.05) indicating amplification of products
      from two disomic loci that share alleles. Meiotic drive was evident at the Afu39
      loci based on a test for random segregation (P < 0.05). Only the expression of
      Afu19 gave evidence of tetrasomic inheritance based on a single progeny
      potentially produced by a double reduction gamete. No evidence for proposed
      octoploid inheritance was observed.

PMID- 11341729
TI  - A restriction fragment length polymorphism based linkage map of a diploid Avena
      recombinant inbred line population.
AB  - A population of 100 F6-derived recombinant inbred lines was developed from the
      cross of two diploid (2n = 14) Avena accessions, CI3815 (A. strigosa) and C11994
      (A. wiestii). Restriction fragment length polymorphism (RFLP) probes previously
      mapped in other grass species were used to develop a framework linkage map
      suitable for comparative genetics. Nine linkage groups were identified among the
      181 loci mapped, with an average interlocus distance of 5 cM, and a total genetic
      map length of 880 cM. A cluster of five tightly linked crown rust resistance
      genes (Pca) was localized on the map, as were five loci identified by disease
      resistance gene analogs from maize, sorghum, and wheat. None of the five loci
      identified by the gene analogs were linked to the Pca locus. The linkage map was
      compared with previously published diploid and hexaploid linkage maps in an
      attempt to identify homologous or homoeologous chromosomes between populations.
      Locus orders and linkage relationships were poorly conserved between the A.
      strigosa x A. wiestii map and other Avena maps. In spite of mapping complications
      due to duplications within a basic genome a well as the allopolyploid
      constitution of many Avena species, such map comparisons within Avena provide
      further evi dence of substantial chromosomal rearrangement between species within
      Avena.

PMID- 11341730
TI  - Candidate disease resistance genes in sunflower cloned using conserved nucleotide
      binding site motifs: genetic mapping and linkage to the downy mildew resistance
      gene Pl1.
AB  - Disease resistance gene candidates (RGCs) belonging to the nucleotide-binding
      site (NBS) superfamily have been cloned from numerous crop plants using highly
      conserved DNA sequence motifs. The aims of this research were to (i) isolate
      genomic DNA clones for RGCs in cultivated sunflower (Helianthus annuus L.) and
      (ii) map RGC markers and Pl1, a gene for resistance to downy mildew (Plasmopara
      halstedii (Farl.) Berl. & de Toni) race 1. Degenerate oligonucleotide primers
      targeted to conserved NBS DNA sequence motifs were used to amplify RGC fragments
      from sunflower genomic DNA. PCR products were cloned, sequenced, and assigned to
      11 groups. RFLP analyses mapped six RGC loci to three linkage groups. One of the
      RGCs (Ha-4W2) was linked to Pl1, a downy mildew resistance gene. A cleaved
      amplified polymorphic sequence (CAPS) marker was developed for Ha-4W2 using gene
      specific oligonucleotide primers. Downy mildew susceptible lines (HA89 and HA372)
      lacked a 276-bp Tsp5091 restriction fragment that was present in downy mildew
      resistant lines (HA370, 335, 336, 337, 338, and 339). HA370 x HA372 F2 progeny
      were genotyped for the Ha-4W2 CAPS marker and phenotyped for resistance to downy
      mildew race 1. The CAPS marker was linked to but did not completely cosegregate
      with Pl1 on linkage group 8. Ha-4W2 was found to comprise a gene family with at
      least five members. Although genetic markers for Ha-4W2 have utility for marker
      assisted selection, the RGC detected by the CAPS marker has been ruled out as a
      candidate gene for Pl1. Three of the RGC probes were monomorphic between HA370
      and HA372 and still need to be mapped and screened for linkage to disease
      resistance loci.

PMID- 11341731
TI  - An integrated restriction fragment length polymorphism--amplified fragment length
      polymorphism linkage map for cultivated sunflower.
AB  - Restriction fragment length polymorphism (RFLP) maps have been constructed for
      cultivated sunflower (Helianthus annuus L.) using three independent sets of RFLP
      probes. The aim of this research was to integrate RFLP markers from two sets with
      RFLP markers for resistance gene candidate (RGC) and amplified fragment length
      polymorphism (AFLP) markers. Genomic DNA samples of HA370 and HA372, the parents
      of the F2 population used to build the map, were screened for AFLPs using 42
      primer combinations and RFLPs using 136 cDNA probes (RFLP analyses were performed
      on DNA digested with EcoRI, HindIII, EcoRV, or DraI). The AFLP primers produced
      446 polymorphic and 1101 monomorphic bands between HA370 and HA372. The
      integrated map was built by genotyping 296 AFLP and 104 RFLP markers on 180 HA370
      x HA372 F2 progeny (the AFLP marker assays were performed using 18 primer
      combinations). The HA370 x HA372 map comprised 17 linkage groups, presumably
      corresponding to the 17 haploid chromosomes of sunflower, had a mean density of
      3.3 cM, and was 1326 cM long. Six RGC RFLP loci were polymorphic and mapped to
      three linkage groups (LG8, LG13, and LG15). AFLP markers were densely clustered
      on several linkage groups, and presumably reside in centromeric regions where
      recombination is reduced and the ratio of genetic to physical distance is low.
      Strategies for targeting markers to euchromatic DNA need to be tested in
      sunflower. The HA370 x HA372 map integrated 14 of 17 linkage groups from two
      independent RFLP maps. Three linkage groups were devoid of RFLP markers from one
      of the two maps.

PMID- 11341732
TI  - Apomixis in Tripsacum: comparative mapping of a multigene phenomenon.
AB  - A relationship has been established between the expression of apomixis in natural
      polyploids of Tripsacum dactyloides and fertility as measured by percent seed
      set. Thus, fertility may be reliably used as a defining phenotype for apomixis
      when scoring the progeny from diploid (2n = 2x = 36) x tetraploid (2n = 4x = 72)
      crosses in Tripsacum. By exploiting the relationship between apomixis and
      fertility, as defined by seed set, analyses were performed on a set of related
      second-generation triploid populations segregating for apomixis. These
      populations were derived from sexual (diploid) x apomictic (tetraploid) crosses.
      Six out of 25 genome-dispersed restriction fragment length polymorphism (RFLP)
      markers co-segregate with fertility. Five of these markers were previously
      reported and include: php20855, tda48, tda53, umc62, and umc83, and are linked to
      Tripsacum genetic linkage groups F, I, H, L, and A, respectively. Significantly,
      we report here the syntenic relationships of the maize chromosome intervals to
      Tripsacum that segregate for numerous meiosis-specific and fertility-associated
      genes. Utilizing RFLP locus comparative mapping based on conservation of
      chromosome (genic) regions between related species, it may be concluded that the
      genes controlling fertility have been preserved in both Tripsacum and maize. A
      sixth marker, umc166, has also been shown to co-segregate with fertility and is
      conserved in both grass species. Specifically, umc166 is linked to Tripsacum
      linkage group D and, by syntenic comparison, to the short arm of maize chromosome
      5. Encoded within this marked interval is the gene Ameiotic1 (Am1) whose function
      is required for the initiation of meiosis in both micro- and megaspore mother
      cells and whose absence of expression in the female is, in all likelihood, a
      prerequisite for the expression of apomixis.

PMID- 11341733
TI  - Genome size in 21 Artemisia L. species (Asteraceae, Anthemideae): systematic,
      evolutionary, and ecological implications.
AB  - Genome size was estimated by flow cytometry in 24 populations belonging to 22
      Artemisia taxa (21 species, 1 with two subspecies), which represent the distinct
      subgenera, life forms, basic chromosome numbers, and ploidy levels in the genus.
      2C nuclear DNA content values range from 3.5 to 25.65 pg, which represents a more
      than sevenfold variation. DNA content per haploid genome ranges from 1.75 to 5.76
      pg. DNA amount is very well correlated with karyotype length and ploidy level.
      Some variations in genome size have systematic and evolutionary implications,
      whereas others are linked to ecological selection pressures.

PMID- 11341734
TI  - Maternal inheritance of plastids in Encephalartos Lehm. (Zamiaceae, Cycadales).
AB  - The mode of inheritance of chloroplast DNA has been determined in Encephalartos
      by employing a restriction fragment length polymorphism analysis of chloroplast
      DNA. Artificial F1 hybrids were produced between a female specimen of E.
      natalensis and a male specimen of E. woodii. The hybridization patterns of all
      hybrids correspond, in all cases, with that of E. natalensis, and are different
      from that of E. woodii, thus indicating the maternal inheritance of cpDNA in
      cycads.

PMID- 11341735
TI  - Identification of X chromosomal restriction fragment length polymorphism markers
      and their use in a gene localization study in Drosophila virilis and D.
      littoralis.
AB  - We have identified six restriction fragment length polymorphism (RFLP) markers
      based on unique gene sequences on the X chromosome of Drosophila virilis and D.
      littoralis. The markers were localized by in situ hybridization on larval
      polytene chromosomes, and the conjugation of the X chromosomes of the two species
      was studied in salivary glands of interspecific hybrid female larvae. The gene
      arrangement of D. virilis and D. littoralis appeared to be very different at the
      proximal end of the X chromosome preventing recombination between RFLP markers
      located in this area. Simple quantitative trait loci (QTL) analysis showed that
      five of our marker genes (including nonA and Dmca1A, previously found to affect
      male courtship song in D. melanogaster) are linked with a gene(s) having a major
      effect on species differences in the male courtship song between D. virilis and
      D. littoralis. This shows that the song gene(s) may be located inside a large X
      chromosomal inversion in D. littoralis (as previously suggested), but that it may
      also be located on an area between this inversion and the centromere, close to
      nonA and Dmca1A. Localization of this gene or gene complex will be continued with
      the aid of our newly identified RFLP markers by making interspecific crosses
      between D. virilis group species with more similar X chromosomes.

PMID- 11341736
TI  - A linkage map of hexaploid oat based on grass anchor DNA clones and its
      relationship to other oat maps.
AB  - A cultivated oat linkage map was developed using a recombinant inbred population
      of 136 F6:7 lines from the cross 'Ogle' x 'TAM O-301'. A total of 441 marker
      loci, including 355 restriction fragment length polymorphism (RFLP) markers, 40
      amplified fragment length polymorphisms (AFLPs), 22 random amplified polymorphic
      DNAs (RAPDs), 7 sequence-tagged sites (STSs), 1 simple sequence repeat (SSR), 12
      isozyme loci, and 4 discrete morphological traits, was mapped. Fifteen loci
      remained unlinked, and 426 loci produced 34 linkage groups (with 2-43 loci each)
      spanning 2049 cM of the oat genome (from 4.2 to 174.0 cM per group). Comparisons
      with other Avena maps revealed 35 genome regions syntenic between hexaploid maps
      and 16-34 regions conserved between diploid and hexaploid maps. Those portions of
      hexaploid oat maps that could be compared were completely conserved. Considerable
      conservation of diploid genome regions on the hexaploid map also was observed (89
      95%); however, at the whole-chromosome level, colinearity was much lower.
      Comparisons among linkage groups, both within and among Avena mapping
      populations, revealed several putative homoeologous linkage group sets as well as
      some linkage groups composed of segments from different homoeologous groups. The
      relationships between many Avena linkage groups remain uncertain, however, due to
      incomplete coverage by comparative markers and to complications introduced by
      genomic duplications and rearrangements.

PMID- 11341737
TI  - Identification of Bilby, a diverged centromeric Ty1-copia retrotransposon family
      from cereal rye (Secale cereale L.).
AB  - A diminutive rye chromosome (midget) in wheat was used as a model system to
      isolate a highly reiterated centromeric sequence from a rye chromosome.
      Fluorescence in situ hybridization (FISH) shows this sequence localized within
      all rye centromeres and no signal was detected on wheat chromosomes. DNA
      sequencing of the repetitive element has revealed the presence of some catalytic
      domains and signature motifs typical of retrotransposon genes and has been called
      the Bilby family, representing a diverged family of retrotransposon-like
      elements. Extensive DNA database searching revealed some sequence similarity to
      centromeric retrotransposons from wheat, barley, and centromeric repetitive
      sequences from rice. Very low levels of signal were observed when Bilby was used
      as a probe against barley, and no signal was detected with rice DNA during
      Southern hybridization. The abundance of Bilby in rye indicates that this family
      may have diverged from other distantly related centromeric retrotransposons or
      incorporated in the centromere but rapidly evolved in rye during speciation. The
      isolation of a rye retrotransposon also allowed the analysis of centromeric
      breakpoints in wheat-rye translocation lines. A quantitative analysis shows that
      the breakpoint in IDS.1RL and 1DL.1RS and recombinant lines containing proximal
      rye chromatin have a portion of the rye centromere that may contribute to the
      normal function of the centromeric region.

PMID- 11341738
TI  - Genome discrimination by in situ hybridization in Icelandic species of Elymus and
      Elytrigia (Poaceae: Triticeae).
AB  - The genome constitution of Icelandic Elymus caninus, E. alaskanus, and Elytrigia
      repens was examined by fluorescence in situ hybridization using genomic DNA and
      selected cloned sequences as probes. Genomic in situ hybridization (GISH) of
      Hordeum brachyantherum ssp. californicum (diploid, H genome) probe confirmed the
      presence of an H genome in the two tetraploid Elymus species and identified its
      presence in the hexaploid Elytrigia repens. The H chromosomes were painted
      uniformly except for some chromosomes of Elytrigia repens which showed extended
      unlabelled pericentromeric and subterminal regions. A mixture of genomic DNA from
      H. marinum ssp. marinum (diploid, Xa genome) and H. murinum ssp. leporinum
      (tetraploid, Xu genome) did not hybridize to chromosomes of the Elymus species or
      Elytrigia repens, confirming that these genomes were different from the H genome.
      The St genomic probe from Pseudoroegneria spicata (diploid) did not discriminate
      between the genomes of the Elymus species, whereas it produced dispersed and
      spotty hybridization signals most likely on the two St genomes of Elytrigia
      repens. Chromosomes of the two genera Elymus and Elytrigia showed different
      patterns of hybridization with clones pTa71 and pAes41, while clones pTa1 and
      pSc119.2 hybridized only to Elytrigia chromosomes. Based on FISH with these
      genomic and cloned probes, the two Elymus species are genomically similar, but
      they are evidently different from Elytrigia repens. Therefore the genomes of
      Icelandic Elymus caninus and E. alaskanus remain as StH, whereas the genomes of
      Elytrigia repens are proposed as XXH.

PMID- 11341739
TI  - Construction of a genetic map of barley (Hordeum vulgare L.) cross 'Azumamugi' x
      'Kanto Nakate Gold' using a simple and efficient amplified fragment-length
      polymorphism system.
AB  - We have devised a simple and efficient amplified fragment-length polymorphism
      (AFLP) system consisting of small slab gels, a discontinuous buffer system, and
      silver staining. Using this system, a single worker developed a barley map with
      227 polymorphic fragments in 2 months. As a mapping population, 99 recombinant
      inbred lines of barley cultivars 'Azumamugi' x 'Kanto Nakate Gold' were used.
      Most of the 227 AFLP fragments showed a Mendelian segregation ratio of 1:1, and
      all were assigned to the seven barley chromosomes. Thus, these fragments are
      useful as molecular markers. They were integrated with 40 previously
      characterized sequence-tagged sites, 3 isozymes, and 2 morphological markers to
      construct an integrated map. The resulting map covered 925.6 cM with 272 markers
      (detecting 150 loci) at an average interval of 6.5 cM/locus. This system greatly
      simplifies map construction.

PMID- 11341740
TI  - Spectral karyotyping (SKY) of mouse meiotic chromosomes.
AB  - The spectral karyotyping procedure of in situ hybridization with chromosome
      specific probes assigns a unique colour code to each of the 21 mouse mitotic
      chromosomes. We have adapted this procedure to meiotic prophase chromosomes, and
      the results show that each of the pachytene or metaphase I bivalents can be
      identified. This technique has the potential to recognize synaptic anomalies and
      chromosome-specific structural and behavioural characteristics. We confirm these
      potentials by the recognition of the heterologous synapsis of the X and Y
      chromosomes and by the variances of synaptonemal complex lengths for each of the
      colour-coded bivalents in eight prophase nuclei.

PMID- 11341741
TI  - Genomic in situ hybridization analysis of a trigenomic hybrid involving Solanum
      and Lycopersicon species.
AB  - A 4x potato (+) tomato fusion hybrid (2n = 4x = 48) was successfully backcrossed
      with a diploid Lycopersicon pennellii (2n = 2x = 24). Genomic in situ
      hybridization (GISH) on somatic and meiotic chromosomes confirmed that the
      progenies were triploids (2n = 3x = 36) and possessed three different genomes:
      potato, tomato, and L. pennellii. Therefore, they have been called trigenomic
      hybrids. Total genomic probes of both Lycopersicon species were found to
      hybridize mutually, whereas the potato genome was clearly differentiated. During
      metaphase I, bivalents were formed predominantly between tomato and L. pennellii
      chromosomes and the univalents of potato chromosomes were most common. Trivalents
      in all cases included homoeologous chromosomes of potato, tomato, and L.
      pennellii. However, the triploids were totally sterile as determined from
      extensive crossing. On chromosome doubling of triploids by shoot regeneration
      from callus, hexaploids (2n = 6x = 72) were obtained. Despite exhibiting clear
      allohexaploid behaviour by forming 36 bivalents at meiosis, these were also
      completely sterile like their triploid counterparts. In spite of this drawback,
      the prospects of chromosome pairing between potato L. pennellii and Solanum
      genomes does open the possibilities for bringing the two genera close.

PMID- 11341742
TI  - A system of rapid isolation of end-DNA from a small amount of fosmid DNA, with
      vector-based PCR for chromosome walking.
AB  - The pBAC 108L and pFos 1 vectors were developed as stable propagation vectors
      which, due to their extremely low copy number, facilitate the cloning of a large
      sized insert containing repeated DNA. However, the low copy number requires
      laborious end-DNA preparation for end sequencing and chromosome walking. Here we
      describe efficient methods for end-DNA isolation. The entire process, including
      small-scale DNA preparation, restriction digestion, self-ligation, and PCR with
      vector-based primers, is carried out in 96-well formats. Using a Fosmid library
      of genomic DNA of Candida albicans, PCR products ranging in size from 0.1 to 8
      kbp were generated from 118 end sequences in 140 reactions from 70 Fosmid clones.
      A single or a prominent band was found in 101 of these reactions. Twenty-six of
      these bands were tested for walking and all of them proved to be specific. Thus,
      the system overcomes the disadvantage caused by low copy number. This system
      allows rapid physical mapping of genomes, and is adaptable for several other
      vectors including BAC (bacterial artificial chromosome), PAC (P1-derived
      artificial chromosome), and YAC (yeast artificial chromosome).

PMID- 11341744
TI  - Free and complexed prostate-specific antigen (PSA) in the early detection of
      prostate cancer.
AB  - We evaluated the analytical performance and diagnostic utility of complexed
      prostate-specific antigen (CPSA) and their ratios, complexed-to-total PSA (C/T
      PSA) and free-to-complexed PSA (F/C PSA), in comparison with the total PSA (TPSA)
      and free-to-total PSA ratio (F/T PSA) as means of diagnosing prostate cancer
      (PC). Samples (n=101) were drawn from men with no evidence of malignancy (n=80)
      and from men with PC (n=21) at biopsy. For determination of the F/T PSA ratio,
      the DPC Immulite-2000 method was used; and the Bayer Immuno-1 CPSA and TPSA
      assays were used to determine the C/T PSA ratio. The Bayer Immuno-1 CPSA assay
      provides accurate and precise CPSA values in human serum. The performance of the
      different forms and ratios was compared using receiver operating characteristic
      curve analysis. CPSA had the greatest area under the curve (AUC, 0.689) although
      it was not statistically different from the other parameters. A cut-off value of
      4.66 ng/ml for CPSA provided a specificity of 38% and a sensitivity of 93%. The
      F/C PSA ratio maintained a sensitivity of 93% and had an increased specificity of
      41%. The measurement of CPSA provides a slight increase in specificity compared
      with the use of the TPSA in the early detection of prostate cancer.

PMID- 11341743
TI  - The effects of impaired trace element status on polymorphonuclear leukocyte
      activation in the development of vascular complications in type 2 diabetes
      mellitus.
AB  - Impaired trace element metabolism may be involved in some of the metabolic
      dysfunctions, and contribute to the development of vascular complications in
      diabetic patients. In order to investigate the relationships among diabetes
      mellitus, trace element status, leukocyte activation and vascular complications,
      55 type 2 diabetic patients (34 with vascular complications and 21 without
      vascular complications) and 50 non-diabetic control subjects were studied. The
      mean leukocyte count (p<0.001), polymorphonuclear elastase (p<0.001), erythrocyte
      malondialdehyde (p<0.001), and glycated haemoglobin (p<0.001) levels, and copper/
      zinc ratio (p<0.001) were found to be higher in diabetic patients than in the
      control group, but serum zinc levels (p<0.001) and erythrocyte superoxide
      dismutase activities (p<0.001) were lower, and serum copper levels showed no
      differences. In patients with vascular complications, the mean leukocyte count
      (p<0.05), zinc (p<0.05), polymorphonuclear elastase (p<0.05), erythrocyte
      malondialdehyde (p<0.001) and glycated haemoglobin (p<0.05) levels, and
      copper/zinc ratio (p<0.001) were significantly different from those patients
      without complications. Closer correlations between the copper/zinc ratio and
      polymorphonuclear elastase (r=0.82, p<0.01), erythrocyte malondialdehyde (r=0.46,
      p<0.05) or erythrocyte superoxide dismutase (r= -0.85, p<0.01) were found in
      patients with vascular complications compared to those without, and all of those
      showed significant relationships with poor glycaemic metabolic control. We
      conclude that zinc deficiency may provoke polymorphonuclear leukocyte activation,
      and contributes to the development of vascular complications in type 2 diabetic
      patients. Furthermore, copper/zinc ratio and polymorphonuclear elastase may be
      used as important markers to evaluate the presence of vascular complications.

PMID- 11341745
TI  - Heterogeneity of DNA methylation status analyzed by bisulfite-PCR-SSCP and
      correlation with clinico-pathological characteristics in colorectal cancer.
AB  - Aberrant DNA methylation has been identified as an important mechanism for
      inactivation of tumor suppressor genes and mismatch repair genes during
      carcinogenesis. We used bisulfite treatment and the PCR-single strand
      conformation polymorphism (SSCP) (BiPS) technique to analyze methylation status
      of the promoter regions of the hMLH1, p16, and HIC1 genes in several cancer cell
      lines and colorectal cancer tissues. The methylation of the hMLH1, p16 and HIC1
      genes was observed in 2, 8, and 13 of 13 cancer cell lines, respectively. The
      SSCP for p16 and HIC1 in each of the methylation-positive cell lines were
      similar, indicating relative homogeneity of methylation status and complete
      methylation in the cell lines. Methylation was observed in 8, 5, and 21 of 25
      colorectal cancer tissues for the hMLH1, p16, and HIC1 genes, respectively. The
      methylated bands revealed by BiPS analysis of the hMLH1 gene were homogeneous,
      whereas those of the p16 and HIC1 genes were different in each case. The
      methylation of the promoter region of the HIC1 gene in colorectal cancer was
      observed most frequently and could serve as a sensitive marker for colorectal
      cancer. Methylation status of the hMLH1 and p16 gene promoters was correlated
      with microsatellite instability status, tumor location, and differentiation but
      not with K-ras mutation or allelic loss of p53.

PMID- 11341746
TI  - Serum amyloid A protein (SAA) in colorectal carcinoma.
AB  - The changes in serum levels of serum amyloid A protein were studied in 67
      patients suffering from colorectal carcinoma and compared to three other major
      acute phase proteins: C-reactive protein, alpha1-antichymotrypsin and alpha1-acid
      glycoprotein. Although the presence of colorectal carcinoma caused an increase in
      serum levels of all the acute phase reactants studied, serum amyloid A protein
      showed the most powerful reaction in pre-operative disease stage, with the mean
      value of 330 mg/l (range 7-2506 mg/l) as compared to the normal values of <1.2
      mg/l obtained in 30 healthy adults. The mean serum amyloid A protein
      concentration increased to 487 mg/l after surgery, declining during the post
      operative clinical course until the sixth chemotherapy cycle (from 167 mg/l to 64
      mg/l), but never returned to the normal range. In the later chemotherapy cycles,
      mean serum amyloid A protein increased to 163 mg/l, probably as a result of the
      disease relapse. According to the statistical relations among exact confidence
      intervals for proportions, serum amyloid A protein showed the best specificity
      for colorectal carcinoma of all the acute phase proteins studied (83-100%) and
      also a sensitivity of 100%. We concluded that serum amyloid A protein seems to be
      a reliable parameter, which could be recommended for clinical routine as a non
      specific tumour marker for colorectal carcinoma.

PMID- 11341747
TI  - Metal exposure from amalgam alters the distribution of trace elements in blood
      cells and plasma.
AB  - Twenty-seven consecutive patients with health problems associated with dental
      amalgam were recruited. In spite of thorough medical examinations, there were no
      diagnoses available. The patient group was dominated by women. A healthy age- and
      sex-matched control group with dental amalgams without symptoms was also
      recruited. Metal level monitoring in plasma and nuclear microscopy of isolated
      individual blood cells were carried out. Significant increases of copper, iron,
      zinc and strontium were found in patient plasma. There was no significant
      difference in plasma selenium between the groups. Mercury was significantly
      increased in patient plasma, although there was overlap between the groups. In
      erythrocytes a significant increase in calcium and a significant decrease in
      magnesium, copper, manganese and zinc were found. Calcium, magnesium, manganese
      and copper increased in patient neutrophil granulocytes. A significant decrease
      was found for zinc. A conspicuous finding was the presence of measurable mercury
      in a few of the cells from the patient but not in the control group. Thus,
      nuclear microscopy of isolated individual blood cells might provide a better
      diagnostic tool for metal exposure than blood plasma measurements.

PMID- 11341748
TI  - Diabetic cataract and the total antioxidant status in aqueous humor.
AB  - Some mechanisms have been proposed for cataract formation in diabetes mellitus
      such as excessive tissue sorbitol concentrations, abnormal glycosylation of lens
      proteins and increased free radical production in the intraocular region. We
      measured total antioxidant status and uric acid levels in aqueous humor from
      diabetic (n=20) and non-diabetic subjects (n=16) with cataracts. The patients
      with diabetes and cataract had significantly lower aqueous humor total
      antioxidant status than those with senile cataract (p = 0.001). Serum and aqueous
      humor uric acid levels were significantly lower in the diabetic cataract group
      compared to the senile cataract group. In the diabetic cataract group, the
      aqueous humor antioxidant status correlated positively with the aqueous humor
      uric acid levels (p < 0.05). The results of this study suggest that reduced
      aqueous humor antioxidant status might be associated with reduced aqueous humor
      uric acid in patients with diabetic cataract. This decrease in aqueous humor uric
      acid levels might lead to the acceleration of cataract formation.

PMID- 11341749
TI  - Candidate gene polymorphisms in cardiovascular disease: a comparative study of
      frequencies between a French and an Italian population.
AB  - A multilocus assay was used to genotype up to 27 variable sites in 15 genes in
      French and Italian, presumed to be healthy populations (n=1480, n=162,
      respectively). These genes are involved in lipid metabolism (APOE, APOB, APOC3,
      CETP, LPL, PON), homocysteine metabolism (CBS, MTHFR), blood viscosity
      (Fibrinogen, FV), platelet aggregation (GpIIIa), leukocyte adhesion (SELE), and
      renin-angiotensin system (AT1R, ACE, AGT). Allele frequencies for all the markers
      were compared between the two populations. Five allele frequencies differed
      between the two European countries: APOB 71Ile (p < 0.001), SELE 98T (p < 0.001),
      SELE 128Arg (p < or = 0.01), APOE E4 (p < or = 0.01) and MTHFR 677T (p < or =
      0.01), suggesting the existence of a north-south gradient in European allele
      frequencies. The other allele frequencies : APOC3 -482T, -455C, 1100T, 3175G,
      3206G; LPL -93G, 9Asn, 291Ser; CETP 405Val; PON 192Arg; ACE Del; AGT 235Thr; AT1R
      1166C; CBS 278Thr, GpIIIa P1A2; Fibrinogen -455A, FV 506Gln and SELE 554Phe, were
      similar between the two populations. They were also similar to those observed in
      other European countries.

PMID- 11341750
TI  - Reference values for plasma dipeptidyl-peptidase IV activity and their
      association with other laboratory parameters.
AB  - In blood, the exopeptidase dipeptidyl-peptidase IV (DPPIV; EC 3.4.14.5) is
      predominantly present in a soluble form in plasma/serum and as an activation
      antigen on the membrane of lymphocytes (CD26). It modifies some important
      biologically active peptides (neuropeptides, chemokines), and a regulatory role
      for DPPIV/CD26 in immune and endocrine processes has been demonstrated. The aim
      of this study was to determine reference values for plasma/serum DPPIV activity
      and to study the association of this activity with a series of biochemical and
      hematological parameters and baseline characteristics such as age, gender, blood
      pressure and body mass index. We studied 481 healthy subjects aged between 19 and
      61 years. The group consisted of 213 men and 268 women equally divided between
      the different categories of age. Among the women, 127 were taking hormone therapy
      (contraception/hormone replacement) and 141 were not. A multiple regression model
      shows that DPPIV activity decreases significantly with age. The activity in women
      is slightly lower than in men. We observed an important association with liver,
      muscle and lipid metabolism-related parameters. In this model, no significant
      contribution of body mass index, blood pressure or hormone therapy could be
      stated.

PMID- 11341751
TI  - Influence of index of individuality on false positives in repeated sampling from
      healthy individuals.
AB  - The index of individuality is defined as the ratio of the within-subject
      biological variation to the between-subject variation, i.e., the variation
      between the biological set-points. It has been disputed whether the index of
      individuality has influence on the usefulness of conventional population-based
      reference intervals. In this investigation we found that, as long as only a
      single sample is taken, for a certain change in an individual's set-point, the
      index of individuality has no influence on the usefulness of reference intervals.
      When two or more samples are taken into account, however, the outcome of the
      measurement is highly dependent on the index of individuality. For a low index,
      repeat measurement has only limited effect on the fraction of false-positive
      results, as the next result will be close to the first, but, when the index is
      high, the fraction of false-positive results will be reduced considerably through
      repeating the test. Moreover, the distribution of biological set-points for which
      the fraction of false-positive results originate is described and the influence
      of analytical imprecision is discussed. The calculations are performed for values
      of the index of individuality from 0 to 2.0 for the traditional 95% reference
      interval based on x +/- 2*s(total) (s(total) = total biological variation), and
      also for a decision limit (cut-off point) x +/- 3*s(total). The numbers are, of
      course, different, but the effects of the index of individuality are the same,
      independent of the chosen cut-off point. This concept is related to the clinical
      classification (diagnosis, prognosis, screening) and the difference from
      different principles of monitoring is discussed. Further, five examples are
      evaluated and aspects of index of individuality in relation to false-positive
      results are discussed.

PMID- 11341752
TI  - Regional reference values for some quantities measured with the ADVIA Centaur
      analyser. A model of co-operation between the in vitro diagnostic industry and
      clinical laboratories.
AB  - This work is a model of co-operation between the in vitro diagnostic industry and
      clinical laboratories for the production of reference values. Thirteen clinical
      laboratories having an ADVIA Centaur analyser and representing the majority of
      the geographical regions of Spain have shared the search for reference
      individuals and the production of reference values for thyrotropin, free
      thyroxine, free triiodothyronine, cobalamine and folate concentrations in serum.
      All the logistic work has been done in co-operation with the Spanish supplier of
      the ADVIA Centaur analyser. The reference limits produced in the virtual
      laboratory are derived from the blend of reference values obtained by each
      laboratory. The multicentre reference limits were estimated according to the
      recommendations of the International Federation of Clinical Chemistry and
      Laboratory Medicine (IFCC).

PMID- 11341753
TI  - Tissue polypeptide-specific antigen (TPS) concentrations in cerebrospinal fluid
      in patients with breast cancer metastases in the central nervous system.

PMID- 11341754
TI  - The measurement of anti-hepatitis C virus antibody in sera using a new generation
      immunoassay.

PMID- 11341755
TI  - Quality specifications for cardiac troponin assays.

PMID- 11341756
TI  - Clinical biological and genetic heterogeneity of the inborn errors of pulmonary
      surfactant metabolism.
AB  - Pulmonary surfactant is a multimolecular complex located at the air-water
      interface within the alveolus to which a range of physical (surface-active
      properties) and immune functions has been assigned. This complex consists of a
      surface-active lipid layer (consisting mainly of phospholipids), and of an
      aqueous subphase. From discrete surfactant sub-fractions one can isolate strongly
      hydrophobic surfactant proteins B (SP-B) and C (SP-C) as well as collectins SP-A
      and SP-D, which were shown to have specific structural, metabolic, or immune
      properties. Inborn or acquired abnormalities of the surfactant, qualitative or
      quantitative in nature, account for a number of human diseases. Beside hyaline
      membrane disease of the preterm neonate, a cluster of hereditary or acquired lung
      diseases has been characterized by periodic acid-Schiff-positive material filling
      the alveoli. From this heterogeneous nosologic group, at least two discrete
      entities presently emerge. The first is the SP-B deficiency, in which an
      essentially proteinaceous material is stored within the alveoli, and which
      represents an autosomal recessive Mendelian entity linked to the SFTPB gene (MIM
      1786640). The disease usually generally entails neonatal respiratory distress
      with rapid fatal outcome, although partial or transient deficiencies have also
      been observed. The second is alveolar proteinosis, characterized by the storage
      of a mixed protein and lipid material, which constitutes a relatively
      heterogeneous clinical and biological syndrome, especially with regard to age at
      onset (from the neonate through to adulthood) as well as the severity of
      associated signs. Murine models, with a targeted mutation of the gene encoding
      granulocyte macrophage colony-stimulating factor (GM-CSF) (Csfgm) or the beta
      subunit of its receptor (II3rb1) support the hypothesis of an abnormality of
      surfactant turnover in which the alveolar macrophage is a key player. Apart from
      SP-B deficiency, in which a near-consensus diagnostic chart can be designed, the
      ascertainment of other abnormalities of surfactant metabolism is not
      straightforward. The disentanglement of this disease cluster is however essential
      to propose specific therapeutic procedures: repeated broncho-alveolar lavages, GM
      CSF replacement, bone marrow grafting or lung transplantation.

PMID- 11341757
TI  - NMR structure of a 2',5' RNA favors A type duplex with compact C2'endo nucleotide
      repeat.
AB  - In order to provide a structural basis for the unusual properties of 2',5'
      nucleic acids, especially their unsuitability as information molecules, we report
      here a high resolution NMR structure of a 2',5' RNA fragment r(GCCGCGGC). It
      forms an A type duplex with C2'endo compact nucleotide repeat, instead of the
      familiar C3'endo compact nucleotide (seen in RNA) supporting the deductions made
      earlier from stereochemical considerations. This data together with the
      observation that 2',5' nucleic acids require mandatory slide and displacement for
      duplex and triplex structure formation suggest their reluctance to form the
      biologically relevant B type duplex. It is argued that this lack of flexibility
      for helical polymorphism and other inadequacies as a consequence of this may be a
      contributing factor for the rejection of 2',5' links by nature. The structure
      exhibits interesting features such as the syn glycosyl conformation for the
      terminal guanine and a hydrogen bond between O3' hydroxyl and anionic oxygen of
      the phosphate.

PMID- 11341758
TI  - Transcriptional regulation of the leptin promoter by insulin-stimulated glucose
      metabolism in 3t3-l1 adipocytes.
AB  - Insulin-stimulated glucose metabolism plays a key role in the regulation of
      leptin mRNA expression and protein secretion. However, it is not known whether
      stimulation of leptin production by glucose metabolism is regulated at the level
      of promoter activation or at a step distal to the promoter. Therefore, in order
      to investigate the transcriptional regulation of the leptin promoter by insulin
      stimulated glucose metabolism, 3T3-L1 cells were transfected with a plasmid
      containing the leptin promoter driving a luciferase reporter gene. Leptin
      promoter activity was increased after 48 hours of treatment by 219 +/- 64 (p =
      0.028) and 225 +/- 69% (p = 0.046) at insulin concentrations of 16 and 160 nM,
      respectively. The activation of the leptin promoter induced by insulin (16 nM)
      was markedly inhibited by 2-deoxy-D-glucose (2-DG, 50 mg/dl), a competitive
      inhibitor of glucose metabolism. The increment of insulin-stimulated leptin
      promoter activation was reduced by 52 +/- 11% (p = 0.028 vs insulin alone). The
      activity of a control plasmid (pGL2-Control) was unaffected by insulin or 2-DG.
      These results provide strong evidence that insulin-stimulated glucose metabolism,
      and not insulin per se, mediates the effects of insulin to increase the
      transcriptional activity of the leptin promoter.

PMID- 11341759
TI  - Downregulation of K(+) channel genes expression in type I diabetic
      cardiomyopathy.
AB  - Type I diabetic cardiomyopathy has consistently been shown to be associated with
      decrease of repolarising K(+) currents, but the mechanisms responsible for the
      decrease are not well defined. We investigated the streptozotocin (STZ) rat model
      of type I diabetes. We utilized RNase protection assay and Western blot analysis
      to investigate the message expression and protein density of key cardiac K(+)
      channel genes in the diabetic rat left ventricular (LV) myocytes. Our results
      show that message and protein density of Kv2.1, Kv4.2, and Kv4.3 are
      significantly decreased as early as 14 days following induction of type I
      diabetes in the rat. The results demonstrate, for the first time, that insulin
      deficient type I diabetes is associated with early downregulation of the
      expression of key cardiac K(+) channel genes that could account for the
      depression of cardiac K(+) currents, I(to-f) and I(to-s). These represent the
      main electrophysiological abnormality in diabetic cardiomyopathy and is known to
      enhance the arrhythmogenecity of the diabetic heart. The findings also extend the
      extensive list of gene expression regulation by insulin.

PMID- 11341760
TI  - Expression of Smads during in vitro transdifferentiation of hepatic stellate
      cells to myofibroblasts.
AB  - TGFbeta is of crucial importance during transdifferentiation of resting retinoid
      storing hepatic stellate cells (HSC) to extracellular matrix producing
      myofibroblasts (MFB) and consequently, inhibition of TGFbeta signal transduction
      is an effective means for preventing experimental fibrosis. We have shown that
      isolated HSC lose TGFbeta-dependent growth control during in vitro activation and
      that alpha2 (I) collagen production in transdifferentiated MFB is TGFbeta
      independent. Furthermore, Smad complexes with SBE binding activity were only
      detected in early cultures of HSC, although TGFbeta receptor types I and II were
      significantly expressed in HSC and MFB. In the present report, we compared the
      expression pattern of TGFbeta downstream mediators, i.e., the Smads, in TGFbeta
      responsive HSC versus nonresponding MFB. The transdifferentiation process was
      monitored by morphology and increasing expression of TGFbeta and alpha-smooth
      muscle actin, and TGFbeta signaling was investigated by (CAGA)(9)-MLP-Luc. The
      expression level of all Smads remained essentially unchanged both during the
      activation process and after TGFbeta-treatment. Smad7 was transiently upregulated
      upon TGFbeta stimulation in quiescent HSC, indicating a negative feed back loop
      in responsive cells. In contrast, MFB neither displayed TGFbeta-inducible nor
      constitutively upregulated Smad7 expression. Instead, Smad3 mRNA was increased in
      MFB. Our data indicate that abrogation of the TGFbeta response in MFB versus HSC
      is not based on different regulation of Smad expression.

PMID- 11341761
TI  - Target genes downregulated by the BCL-6/LAZ3 oncoprotein in mouse Ba/F3 cells.
AB  - The BCL-6/LAZ3 gene encodes a zinc-finger transcriptional repressor and is
      located at the breakpoint of the 3q27-associated translocations that occur most
      frequently in non-Hodgkin's lymphomas (NHLs). A number of chromosomal
      translocations involving BCL-6 have been analyzed, but the biological functions
      of this protein remain obscure. To examine cell responses and target genes
      related to the BCL-6 signaling pathway, we established Ba/F3 pro-B cells carrying
      a human BCL-6 transgene that is inducible under control of the lactose operon.
      Using a cDNA array hybridization technique, we found that the induced BCL-6
      protein can downregulate the expressions of the genes, cyclin A2, chemokine
      receptor CXCR4, and insulin-like growth factor binding protein-4 (IGFBP-4) in the
      Ba/F3 cells. Northern blot analysis established that the expressions of these
      genes were indeed downregulated by the induced BCL-6 protein but in a somewhat
      different manner. The induced BCL-6 protein also inhibited cell proliferation of
      Ba/F3 cells. These findings strongly suggest that three key genes, namely cyclin
      A2, CXCR4, and IGFBP-4 may play a role in the downstream of the BCL-6 signaling
      pathway during B-lymphoid differentiation.

PMID- 11341762
TI  - Characterization of the bi-directional transcriptional control region between the
      human UFD1L and CDC45L genes.
AB  - The human UFD1L and CDC45L genes, adjacently located in the head-to-head
      direction on chromosome 22q11, are separated by a 884 base-pair (bp) segment
      constituting the putative transcriptional control region. In this region we
      mapped one transcription start site at 69 bp upstream of UFD1L gene, and one
      major and one minor start sites at 76 bp and 503 bp upstream of CDC45L gene,
      which are to center in the putative core promoters designated as P(UFD1L),
      P(CDC45L/major), and P(CDC45L/minor), respectively. The three core promoters
      lacked a TATA-motif and had a high GC-content. To determine the approximate
      ranges for the regulatory promoters, the 884-bp fragment or those with a series
      of deletions were placed between firefly and renilla luciferase genes present in
      the head-to-head direction in a single plasmid, and the resulting plasmids were
      assayed for the two transiently induced enzyme activities. The P(UFD1L) and
      P(CDC45L/major) regulatory promoters were within 418 and 454 bp upstream of the
      respective start sites and their greater parts were not overlapping. The activity
      of P(CDC45L/minor) regulatory promoter was markedly enhanced when P(CDC45L/major)
      and its regulatory promoter were deleted. The deletion analyses revealed the
      basal activities of the three core promoters, which were enhanced by
      approximately twofold by the respective regulatory promoters, on the transfected
      DNA templates.

PMID- 11341763
TI  - Promoter analysis for daily expression of Drosophila timeless gene.
AB  - Drosophila circadian clock gene timeless (tim) displays circadian oscillation in
      its mRNA level, and such oscillation is transcriptionally regulated. The promoter
      region up to -756 of tim is suggested to promote the circadian mRNA expression,
      however, the role of the sequence upstream of tim promoter region in the
      transcriptional regulation is still unrevealed. We novelly isolated and
      determined tim 5'-flanking sequence -2764 to -757, and found a putative cAMP
      response element, six regions of the half site for PAR-basic leucine zipper
      transcription factors and six nonpalindromic E-boxes. Our in vivo reporter assay
      showed that 966 bp of tim promoter region, including a palindromic CACGTG E-box
      and a half site of PAR-basic leucine zipper transcription factors, was minimally
      required for its daily mRNA expression. While, the deletion of the 5'-flanking
      region -1970 to -967 caused a slight decrease in the reporter mRNA levels. These
      results indicate that the 5'-flanking sequence upstream of the promoter region
      have a role in the daily regulation of tim mRNA expression in Drosophila.

PMID- 11341764
TI  - Gap junction-dependent increases in smooth muscle cAMP underpin the EDHF
      phenomenon in rabbit arteries.
AB  - We have investigated the role of cAMP in nitric oxide (NO)- and prostanoid
      independent vascular relaxations evoked by acetylcholine (ACh) in isolated
      arteries and perfused ear preparations from the rabbit. These EDHF-type responses
      are shown to be associated with elevated cAMP levels specifically in smooth
      muscle and are attenuated by blocking adenylyl cyclase or protein kinase A (PKA).
      Relaxations are amplified by 3-isobutyl-1-methylxanthine, which prevents cAMP
      hydrolysis, while remaining susceptible to inhibition by the combination of two
      K(Ca) channel blockers, apamin and charybdotoxin. Analogous endothelium- and cAMP
      dependent relaxations were evoked by cyclopiazonic acid (CPA) which stimulates
      Ca(2+) influx via channels linked to the depletion of Ca(2+) stores. Responses to
      ACh and CPA were both inhibited by interrupting cell-to-cell coupling via gap
      junctions with 18alpha-glycyrrhetinic acid and a connexin-specific Gap 27
      peptide. The findings suggest that EDHF-type responses are initiated by
      capacitative Ca(2+) influx into the endothelium and propagated by direct
      intercellular communication to effect relaxation via cAMP/PKA-dependent
      phosphorylation events in smooth muscle.

PMID- 11341765
TI  - Identification of an alternative transcript of ABCA1 gene in different human cell
      types.
AB  - We have observed two ABCA1 gene transcripts in human skin fibroblasts. The RT-PCR
      amplification of the exon 3-exon 8 region generated a normal fragment (740 bp)
      and an abnormal fragment (600 bp) in a ratio ranging from 3:1 to 8/9:1. These two
      transcripts were present in other cells such as leukemia T-cells, endothelial and
      smooth muscle cells as well human hepatoma cells (HepG2). Restriction enzyme
      analysis and sequencing indicated that in the abnormal fragment exon 3 was
      followed by exon 5. The complete skipping of exon 4 leads to a premature stop and
      a predicted translation product of 74 amino acids. The ratio between the normal
      and alternative transcript is not affected by variation in ABCA1 gene expression
      induced by incubating cells in serum-free medium and in the presence of
      cholesterol. It is possible that this alternative splicing represents as
      mechanism that regulates the ABCA1 content in tissues.

PMID- 11341766
TI  - Critical sites for the interaction between IL-2Rgamma and JAK3 and the following
      signaling.
AB  - JAK3 is the only known protein tyrosine kinase associating with IL-2Rgamma. This
      interaction is supposed to be very important to IL-2 signaling. In order to
      identify the critical residues for these two molecular interactions and the
      following signal events, various mutants of gammac and JAK3 were constructed on
      the basis of computer analysis. The direct interaction was determined via the
      yeast two-hybrid system, while the signaling was analyzed with reporter genes
      under the control of the c-fos, c-myc, or tnf-beta promoters, respectively.
      Results showed that there are two key sites on gammac involved in this
      interaction and the following signal transduction: the critical one is E327 via
      electrostatic interaction, the other is L293 via hydrophobic interaction. As to
      JAK3, the data indicated that Y100 is important for the interaction with gammac.
      These results also document that the requirement for interaction between gammac
      and JAK3 is different to activate different signaling pathways mediated by
      gammac, such as c-fos, c-myc, and JAK-STAT.

PMID- 11341767
TI  - Identification of HGF-like protein as a novel neurotrophic factor for avian
      dorsal root ganglion sensory neurons.
AB  - HGF-like protein (HLP) is a member of the hepatocyte growth factor (HGF) family.
      Although HGF is shown to have neurotrophic activities on many of CNS and PNS
      neurons, the role of HLP in the nervous system is poorly understood despite the
      knowledge that Ron/HLP receptor is expressed in embryonic neurons. Here we show
      that HGF but not HLP promotes neurite extension and migration emanating from
      chick embryonic day 9 (E9) dorsal root ganglia (DRG) explants in the presence of
      low levels of NGF, however, HLP does promote neurite extension and cellular
      migration from E15 chick DRG explants with low levels of NGF. Ron-Fc, a chimeric
      molecule composed of the extracellular domain of Ron fused with immunoglobulin
      Fc, eliminated activities of HLP, such as cellular migration and long neurite
      extension emanating from E15 DRG explants in the presence of NGF, but did not
      eliminate short neurites. These results suggested that promotion of long neurite
      extension and migration depends on activities of HLP through its receptor/Ron.
      Taken together, we propose that HLP may play an important role in chick sensory
      ganglia at relatively late stages of development. This is the first evidence that
      HLP functions as a neurotrophic factor.

PMID- 11341768
TI  - Role of FK506-binding protein 12 in development of the chick embryonic heart.
AB  - A cDNA encoding chicken FK506-binding protein 12 (FKBP12) was isolated and
      sequenced. The predicted amino acid sequence of the chicken protein shows high
      homology to those of FKBP12 proteins of other species ranging from human to frog.
      The possible role of FKBP12 in chick embryonic cardiac development was examined.
      Northern blot analysis revealed that FKBP12 mRNA is distributed widely in chick
      embryos, being especially abundant in the heart; the amount of FKBP12 mRNA in the
      embryonic heart decreased with time. Administration of FK506 to chick embryos at
      7 to 9 days resulted in marked cardiac enlargement. FK506 also reduced the
      expression of myosin, induced a more elongated cell morphology, and impaired
      network formation in cultured chick embryonic cardiomyocytes. These results
      suggest that FKBP12 is important in the regulation of contractile function and
      phenotypic expression in chick cardiomyocytes during embryonic development.

PMID- 11341769
TI  - The invariant F283 and its strategic position in the hydrophobic cleft of
      Streptomyces jumonjinensis isopenicillin N synthase active site are functionally
      important.
AB  - Isopenicillin N synthase (IPNS) and related non-haem iron-binding enzymes
      including deacetoxycephalosporin C synthase (DAOCS) are proposed to have
      structurally similar active centers. Sequence alignment and computational
      structural analyses of predicted structures revealed 11 highly conserved
      hydrophobic amino acid residues in 134 IPNS-related enzymes form a contiguous
      hydrophobic patch in the IPNS active center, wherein F283 is strategically
      positioned. The investigation of single and double mutations at F283, adjacent
      (L284) and proximal sites (N285 and S216) of Streptomyces jumonjinensis IPNS
      advocate the explicit importance of the phenyl ring at position 283. A similarly
      placed phenylalanine (F264) in DAOCS was found to be also crucial for its enzyme
      activity.

PMID- 11341770
TI  - Cloning, expression, and mapping of a mouse gene, Uchl4, highly homologous to
      human and mouse Uchl3.
AB  - Ubiquitin carboxyl-terminal hydrolases (UCHs) are implicated in the proteolytic
      processing of polymeric ubiquitin. We have isolated a novel mouse gene for
      ubiquitin carboxyl-terminal hydrolase isozyme L4. The gene named Uchl4 encodes a
      novel member of the family of ubiquitin carboxyl-terminal hydrolases (UCHs) whose
      predicted amino acid sequence shows 95% identity to mouse UCH-L3 and 94% identity
      to human UCH-L3. Genomic structure, chromosome localization, and expression
      pattern of Uchl3 and Uchl4 were characterized in the mouse. Both Uchl3 and Uchl4
      were expressed in various tissues examined; however, expression level was quite
      lower in Uchl4. While Uchl3 consists of at least 9 exons spanning about 12 kb,
      Uchl4 was an intronless gene with a size of about 2 kb. By PCR-based analysis
      with T31 radiation hybrid mapping panel, Uchl3 and Uchl4 were mapped on mouse
      chromosome 9 and 14, respectively.

PMID- 11341771
TI  - Identification of a nuclear variant of MGEA5, a cytoplasmic hyaluronidase and a
      beta-N-acetylglucosaminidase.
AB  - MGEA5 was originally identified to be a novel human hyaluronidase, which is
      immunogenic in meningioma patients. Recently an N-acetylglucosaminidase was
      reported with identical sequence. Here, we define the origin of a splice variant
      by determining the genomic organization of the mgea5 gene. We find the splice
      variant missing a putative acetyltransferase domain of MGEA5. As for evolutionary
      analysis, we show that the MGEA5 is highly conserved in higher eukaryotes. As for
      expression analysis, we find both mRNA variants ubiquitously expressed in various
      human tissues and throughout mouse development. We generated polyclonal
      antibodies against MGEA5s/5 and identified proteins of 75 and 130 kDa, indicating
      posttranslational modifications of the larger protein. Cell fractionation
      revealed the cytoplasmic/cytoskeletal localization of the 130-kDa protein and the
      nuclear localization of the 75-kDa protein. We propose a model in which MGEA5
      functions both as a hyaluronidase and an N-acetylglucosaminidase.

PMID- 11341772
TI  - ERK mediates effects of glycated albumin in mesangial cells.
AB  - The alterations in glomerular cell biology induced by glycated albumin resemble
      those caused by high ambient glucose, but are operative in physiologic (5.5 mM)
      glucose concentration. Recently, high glucose has been shown to activate
      extracellular signal-related kinase (ERK) in mesangial cells, but whether the
      mitogen-activated protein kinase (MAPK) cascade participates in signal
      transduction triggered by glycated albumin is unknown. Using a specific inhibitor
      of MAPK/ERK kinase, we demonstrate for the first time that activation of ERK is
      required for the inhibition of cell growth and enhanced elaboration of
      extracellular matrix protein provoked by glycated albumin. These findings
      indicate that the MAPK/ERK pathway mediates biologic activities of this glycated
      protein.

PMID- 11341773
TI  - A house fly gene homologous to the zinc finger proto-oncogene Gfi-1.
AB  - Gfi-1 was first cloned from rats (and subsequently from mice, chickens, and
      humans) and was found to be a 55-kDa protein that bound to DNA in a sequence
      specific manner to act as a transcriptional repressor and proto-oncogene. Using
      PCR, a Gfi-1 homologous cDNA (mdGfi-1) was cloned from the house fly, Musca
      domestica. Comparison of the mdGfi-1-deduced amino acid sequence with those of
      vertebrates indicates only moderate overall homology (40.9-43.0% identity).
      However, these proteins are highly conserved when the zinc finger domains are
      compared, with mdGfi-1 having 81.0-82.2% identity to the vertebrate homologues.
      Within each of the six zinc finger domains there are three amino acids that are
      predicted to contact the DNA and these amino acids are 100% identical for all six
      domains for all species. Given that Gfi-1 is highly conserved from insects to
      vertebrates suggests this may be an important transcription factor in many taxa.

PMID- 11341774
TI  - Spermine supports catalysis of hairpin ribozyme variants to differing extents.
AB  - Because of the ability to cleave RNA substrates in trans, the hairpin ribozyme
      has great potential for therapeutic application. Activity of a three-stranded
      version of the minimal truncated form is enhanced by the presence of the
      polyamine spermine. Since spermine is the most abundant polyamine in eucariots,
      improved prospects for the hairpin ribozyme as therapeutic agent were predicted.
      We have found that not all hairpin ribozyme variants accept spermine equally well
      as counter-ion. Particularly the two-stranded versions commonly used for
      therapeutic studies show rather decreased activity when spermine is present. We
      have investigated a number of hairpin ribozyme derivatives regarding their
      ability to carry out spermine supported catalysis. Among the studied structures a
      two-stranded reverse-joined hairpin ribozyme displayed the highest cleavage rates
      in a synergistic mixture of magnesium ions and spermine. The specific features of
      this ribozyme along with its potential for in vivo application are discussed.

PMID- 11341775
TI  - Histone acetylation induced by granulocyte colony-stimulating factor in a map
      kinase-dependent manner.
AB  - Histone acetylation has been shown to affect chromatin structure and gene
      expression. The mitogen-activated protein (MAP) kinase pathway is activated by a
      number of cytokines and plays critical roles in hematopoietic cell survival,
      proliferation, and differentiation. We focused on the part of the MAP kinase
      cascade and granulocyte colony-stimulating factor (G-CSF)in histone acetylation
      at one of the critical myeloid differentiation-associated genes, myeloperoxidase
      (MPO). G-CSF caused rapid acetylation of histone H3 and H4 at the promoter of MPO
      as revealed by chromatin immunoprecipitation. In addition, CBP and p300 were
      recruited to the promoter in response to G-CSF. Furthermore, we showed that rapid
      histone acetylation induced by G-CSF is MAP kinase-dependent. These results
      illustrate how myeloid-differentiating signals via G-CSF may be coupled with
      histone acetylation during the process of gene expression.

PMID- 11341776
TI  - Nongenomic estrogen action in human lung myofibroblasts.
AB  - Recent studies have suggested that the antiproliferative effects of E2 may be
      mediated through a nongenomic action. Herein, we asked whether nongenomic
      estrogen action regulates phosphorylation of Raf1 and ERK1/2 mitogen-activated
      protein (MAP) kinase in lung myofibroblasts. We demonstrated that lung
      myofibroblasts, incubated in the presence of E2, showed a rapid phosphorylation
      on serine-259 of Raf1 and tyrosine-204 of ERK1/2 MAP kinase at 15 min, by
      approximately 3- and 5-fold, respectively. This phosphorylation was followed by
      dephosphorylation between 30 and 60 min. Western blot analysis showed that E2
      regulates tyrosine phosphorylation of four main cytoplasmic proteins in lung
      myofibroblasts, of 42, 44, 70 and 100 kDa. Furthermore, our results indicated
      that E2 inhibits cell proliferation (BrdU index) in lung myofibroblasts by
      approximately 30% (P < 0.01). These data provide evidence that nongenomic action
      of E2, regulates both serine and tyrosine phosphorylation of cytoplasmic proteins
      in lung myofibroblasts, including Raf1 and ERK1/2 MAP kinase, which may regulate
      proliferation in lung myofibroblasts.

PMID- 11341777
TI  - alpha(6) Integrin is the main receptor of human papillomavirus type 16 VLP.
AB  - The present study was performed to determine the specific receptor of type HPV-16
      using recombinant human papillomavirus-like particle (HPV-16 L1-VLP). The
      expression levels of alpha(6), beta(1), and beta(4) integrins were determined and
      compared with the amount of HPV-VLP binding in ten cell lines by flow cytometry.
      Our results show that the amount of VLP binding and the expression level of
      alpha(6) integrin are correlated, which was confirmed by an inhibition experiment
      using antibodies and by immunocytochemistry. Both the expression level of
      alpha(6) integrin and the amount of HPV-VLP binding were high in cervical cancer
      cell lines, as the type HPV-16 is the main cause of cervical cancer. The degree
      of binding of HPV-VLP matched the alpha(6) integrin expression level in cell
      lines but was not correlated with beta(1) and beta(4) levels, which suggests that
      alpha(6) integrin is the main receptor of HPV type 16.

PMID- 11341778
TI  - Identification of pristanal dehydrogenase activity in peroxisomes: conclusive
      evidence that the complete phytanic acid alpha-oxidation pathway is localized in
      peroxisomes.
AB  - Phytanic acid (3,7,11,15-tetramethylhexadecanoic acid) is a branched-chain fatty
      acid which, due to the methyl-group at the 3-position, can not undergo beta
      oxidation unless the terminal carboxyl-group is removed by alpha-oxidation. The
      structure of the phytanic acid alpha-oxidation machinery in terms of the
      reactions involved, has been resolved in recent years and includes a series of
      four reactions: (1) activation of phytanic acid to phytanoyl-CoA, (2)
      hydroxylation of phytanoyl-CoA to 2-hydroxyphytanoyl-CoA, (3) cleavage of 2
      hydroxyphytanoyl-CoA to pristanal and formyl-CoA, and (4) oxidation of pristanal
      to pristanic acid. The subcellular localization of the enzymes involved has
      remained enigmatic, with the exception of phytanoyl-CoA hydroxylase and 2
      hydroxyphytanoyl-CoA lyase which are both localized in peroxisomes. The oxidation
      of pristanal to pristanic acid has been claimed to be catalysed by the microsomal
      aldehyde dehydrogenase FALDH encoded by the ALDH10-gene. Making use of mutant
      fibroblasts deficient in FALDH activity, we show that phytanic acid alpha
      oxidation is completely normal in these cells. Furthermore, we show that
      pristanal dehydrogenase activity is not fully deficient in FALDH-deficient cells,
      implying the existence of one or more additional aldehyde dehydrogenases reacting
      with pristanal. Using subcellular localization studies, we now show that
      peroxisomes contain pristanal dehydrogenase activity which leads us to conclude
      that the complete phytanic acid alpha-oxidation pathway is localized in
      peroxisomes.

PMID- 11341779
TI  - Tryptophan-216 is essential for the transglycosylation activity of endo-beta-N
      acetylglucosaminidase A.
AB  - Endo-beta-N-acetylglucosaminidase from Arthrobacter protophormiae (Endo-A) has a
      high level of transglycosylation activity. To determine which amino acids are
      involved in this activity, we employed deletion analysis, as well as random and
      site-directed mutagenesis. Using PCR random mutagenesis, 11 mutants with greatly
      decreased levels of enzyme activity were isolated. Six catalytically essential
      amino acids were identified by site-directed mutagenesis. Mutants E173G, E175Q,
      D206G, and D270N had markedly reduced hydrolysis activity, while mutants V109D,
      E173D, and E173Q lost all enzymatic activity, indicating that Val-109 and Glu-173
      are important for the catalytic function. Moreover, we isolated a random mutation
      that abolished the transglycosylation activity without affecting the hydrolysis
      activity. The Trp-216 to Arg mutation was identified, by site-directed
      mutagenesis, as that responsible for the loss of transglycosylation activity.
      While other mutants of Trp-216 showed reduced activity, mutation to another
      positively charged residue (Lys) also abolished the transglycosylation activity.
      Sequence comparison with two other endo-beta-N-acetylglucosaminidases, that
      possess transglycosylation activity and that have been cloned recently, reveals a
      high degree of identity in the N-terminal regions of the three enzymes. These
      results indicate that the tryptophan residue at position 216 of Endo-A has a key
      role in the transglycosylation.

PMID- 11341780
TI  - Abnormal calcium homeostasis in fibroblasts from patients with Leigh disease.
AB  - Recently, we reported that in various cell lines under conditions of
      deenergization of the mitochondrial membrane, the release of Ca(2+) from the
      endoplasmic reticulum (ER) does not produce the expected activation of store
      operated calcium channels (SOCs) in the plasma membrane. In the present work, we
      examined the activation of SOCs in fibroblasts derived from three patients with
      Leigh disease (LS). We identified mutations in the SURF-1 gene in all these
      cells. Consequently, cytochrome oxidase (COX) deficiency was found in all these
      (LS(COX)) cell lines and, thus, the main mitochondrial mechanism of generation of
      the electrochemical proton gradient on the mitochondrial membrane was naturally
      depressed. We demonstrated that, in untreated LS(COX) fibroblasts, the rate of
      Ca(2+)-inflow through SOCs was low compared to the fibroblasts from healthy
      individuals even after thapsigargin-induced maximal release of Ca(2+) from the
      ER. Moreover, the pretreatment of LS(COX) fibroblasts with a protonophore did not
      modify this rate. Thus, in LS(COX) fibroblasts, the activation of SOCs was
      naturally impaired. Our findings suggest that altered calcium metabolism, apart
      from severe energy production failure, may also contribute to developing
      pathological conditions in patients with COX-deficient Leigh disease related to
      SURF-1 gene mutation.

PMID- 11341781
TI  - Relative contribution of hemopoietic and pulmonary parenchymal cells to lung
      inducible nitric oxide synthase (inos) activity in murine endotoxemia.
AB  - Acute lung injury is an important feature of sepsis and increased iNOS expression
      and NO production contribute to the pathogenesis of this syndrome. We generated
      bone marrow-transplanted chimeric mice with iNOS expression limited to either
      inflammatory or pulmonary parenchymal cells, and assessed pulmonary iNOS activity
      and systemic levels of NO metabolites in an endotoxemic model of sepsis. We found
      that while both pulmonary parenchymal cells and inflammatory cells contribute to
      the increased lung iNOS activity in endotoxemia, pulmonary parenchymal cells
      contribute to a significantly greater degree. Using measurement of plasma NO(
      )(x), whole body NO production was assessed in this model. We found that the main
      source of NO(-)(x) was again, parenchymal cells and not inflammatory cells. This
      is the first study to demonstrate that most of the increased NO production in
      this model of endotoxemic sepsis derives from parenchymal cells rather than
      inflammatory cells.

PMID- 11341782
TI  - Activation and apoptosis of murine peritoneal macrophages by acute cold stress.
AB  - Effects of acute cold stress (5 degrees C for 24 h) on the functions of
      peritoneal macrophages and the mechanisms for controlling host homeostasis were
      investigated in mice. Phagocytic activity and expression of the cell surface
      adhesion molecule CD11b/CD18 were markedly increased in peritoneal exudate cells
      by acute cold stress. These alterations were attributable to an increased number
      and phenotypical changes of adherent cells from acute cold-stressed mice. On the
      other hand, a lipopolysaccharide-induced activity of src-family tyrosine kinase
      Fgr, an expression of interleukin-1beta (IL-1 beta) mRNA, and a bioactivity of IL
      1 in the culture supernatants of adherent cells from acute cold-stressed mice
      were markedly lower than those from control mice. A time course study revealed
      that the number of adherent cells in peritoneal exudate cells was markedly
      increased in mice exposed to cold for 24 h but returned to normal numbers when
      mice were exposed to cold for 72 h. DNA fragmentation and Annexin-V(+) cells were
      observed in peritoneal exudate cells from acute-cold stressed mice. Thus, cold
      stress activated macrophages but these macrophages were destined to be eliminated
      by apoptosis.

PMID- 11341783
TI  - Exposure of RBL-2H3 mast cells to Ag(+) induces cell degranulation and mediator
      release.
AB  - There is a growing need to understand the impact of environmental sulfhydryl
      group-reactive heavy metals on the immune system. Here we show that Ag(+) induces
      mast cell degranulation, as does the aggregation of the high affinity
      immunoglobulin E receptor (FcepsilonRI). Micromolar quantities of Ag(+)
      specifically induced degranulation of mast cell model rat basophilic leukemia
      (RBL-2H3) cells without showing cytotoxicity. The Ag(+)-mediated degranulation
      could be observed as rapidly as 5 min after the addition of the ions. Ag(+) also
      induced a rapid change in tyrosine phosphorylation of multiple cellular proteins
      including the focal adhesion kinase but not Syk kinase. The Syk-selective
      inhibitor piceatannol and the Src family-selective tyrosine kinase inhibitor PP1
      dose-dependently inhibited FcepsilonRI-mediated degranulation, whereas neither
      compound inhibited the Ag(+)-mediated degranulation. Furthermore, likewise
      FcepsilonRI aggregation, Ag(+) also induced leukotriene secretion. These results
      show that Ag(+) activates RBL-2H3 mast cells through a tyrosine phosphorylation
      linked mechanism, which is distinct from that involved in FcepsilonRI-mediated
      activation.

PMID- 11341784
TI  - Identification of MUC1 proteolytic cleavage sites in vivo.
AB  - Mucins are high molecular weight glycoproteins that provide a protective layer on
      epithelial surfaces and are involved in cell-cell interactions, signaling, and
      metastasis. The identification of several membrane-tethered mucins, including
      MUC1, MUC3, MUC4, and MUC12, has incited interest in the processing of these
      mucins and the mechanisms that govern their release from the cell surface. MUC1
      consists of an extracellular subunit and a membrane-associated subunit. The two
      moieties are produced from a single precursor polypeptide by an early proteolytic
      cleavage event but remain associated throughout intracellular processing and
      transport to the cell surface. We identified the MUC1 proteolytic cleavage site
      and showed it to be identical in pancreas and colon cell lines and not to be
      influenced by the presence of heavily glycosylated tandem repeats. The MUC1
      cleavage site shows homology with sequences in other cell-surface-associated
      proteins and may represent a common mechanism for processing of these molecules.

PMID- 11341785
TI  - Transforming growth factor beta(2) lowers the incidence of incisional hernias.
AB  - BACKGROUND: Approximately 200,000 incisional hernias are repaired annually in the
      United States. The high incidence (11-20%) and recurrence rate (24-54%) for
      incisional hernias have not changed appreciably in 75 years. Mechanical advances
      in suture material, incision orientation, and closure technique have failed to
      eliminate this common surgical complication. A biological approach to acute wound
      failure may offer a new strategy. METHODS: A rodent incisional hernia model was
      used. Seventy rats underwent 5-cm midline celiotomies and were closed with fine,
      fast-absorbing sutures to induce intentional acute wound failure. Group 1
      received no other treatment. The midline fascia in groups 2 and 3 was injected
      immediately prior to incision with 100 microl of vehicle alone or vehicle
      containing 1 microg of transforming growth factor beta(2) (TGF-beta(2)). Necropsy
      was performed on Postoperative Day 28 and the wounds were examined for
      herniation. RESULTS: Incisional hernias developed in 88% (35/40) and 79% (11/14)
      of untreated incisions and those treated with vehicle alone. No hernias formed in
      the TGF-beta(2)-treated incisions (0/16, P < 0.05). Standard histology and
      immunohistochemistry demonstrated enhanced macrophage, lymphocyte, and fibroblast
      chemotaxis and increased collagen I and III production in TGF-beta(2) treated
      incisions. CONCLUSIONS: Treatment of abdominal wall fascial incisions with TGF
      beta(2) prevented the development of incisional hernias in this rat model. TGF
      beta(2) stimulated fascial macrophage and fibroblast chemotaxis as well as acute
      wound collagen production. A biological approach such as this may reduce the
      incidence of incisional hernia formation in humans.

PMID- 11341786
TI  - Expression of a dominant negative inhibitor of NF-kappaB protects MIN6 beta-cells
      from cytokine-induced apoptosis.
AB  - BACKGROUND: Islet graft injury by cytokines released from inflammatory cells
      (macrophages) that infiltrate the transplant site is an important mechanism of
      early islet transplant dysfunction. This detrimental "cytokine effect" is thought
      to be mediated by NF-kappaB-dependent up-regulation of iNOS gene expression and
      increased nitric oxide (NO) production by the islet. We attempted to make a beta
      cell resistant to cytokine-induced apoptosis by transfecting the parent line with
      a dominant negative inhibitor of NF-kappaB. METHODS: A flag-tagged IkappaBalphaM
      cDNA subcloned into an SFFV-neo vector was used to transfect parent beta-Cell
      line MIN6. MIN6 and the resultant mutant (2Bm) were cultured for 24 h in a
      cytokine mixture including IL-1beta (50 units/mL), TNF-alpha (1000 units/mL), and
      IFN-gamma (750 units/mL) and cotreated with either the iNOS inhibitor L-NMMA (1
      mM) or the caspase inhibitor Z-VAD (0.1 mM). NF-kappaB translocation was
      determined by gel shift. Nitrite production was determined by the Griess
      reaction. Apoptosis was determined by flow cytometry. RESULTS: When treated with
      cytokine 2Bm demonstrated significantly less NF-kappaB nuclear translocation,
      nitrite production, and apoptosis than parent MIN6. The rate of apoptosis in
      cytokine-treated 2Bm was a third less than that for cytokine-treated MIN6 and was
      similar to MIN6 cotreated with L-NMMA. Z-VAD cotreatment completely eliminated
      apoptosis in both MIN6 and 2Bm. CONCLUSIONS: Cytokine-induced cell death in the
      MIN6 beta-cell line involves mechanisms that are, in part, NF-kappaB and NO
      dependent. Inhibition of NF-kappaB and NO production by the dominant negative
      inhibitor of NF-kappaB is cytoprotective. This type of genetic modification may
      prove to be one avenue for improving efficacy of islet transplantation.

PMID- 11341787
TI  - FRAP-p70s6K signaling is required for pancreatic cancer cell proliferation.
AB  - BACKGROUND: FRAP-p70s6K signaling regulates mitogenic responses to growth factors
      in eukaryotic cells. Constitutive p70s6K activation occurs in some human
      malignancies and may contribute to dysregulated cell growth. We examined whether
      inhibition of this pathway affects mitogen-induced proliferation and cell cycle
      progression of human pancreatic cancer cells in vitro. METHODS: Quiescent BxPC3
      and Panc-1 human pancreatic cancer cells treated with or without 20 ng/mL
      rapamycin (FRAP inhibitor) were repleted with 10% FCS to induce cell cycle entry.
      Proliferation was measured with MTT assay. Cell cycle and apoptosis were
      determined by FACS analysis. Phosphorylation of p70s6K, Akt, and cdc2 was
      evaluated by Western blot. Statistical analysis was by two-tailed t test (P <
      0.05). RESULTS: Rapamycin (Rapa) inhibited the phosphorylation of p70s6K while
      inducing G(1) cell cycle arrest (P < 0.005). In both cell lines, Rapa inhibited
      serum-induced proliferation (P < 0.05) without affecting apoptosis. Cdc2
      phosphorylation was inhibited by 15 min with Rapa (not shown), consistent with
      cell cycle arrest. Akt phosphorylation was not affected, indicating FRAP
      specificity of Rapa. CONCLUSIONS: FRAP-p70s6K signaling appears to be necessary
      for G(1)-to-S phase progression and proliferation in pancreatic cancer cells.
      This supports earlier work demonstrating a similar regulatory role for PI-3'
      kinase, an upstream activator of FRAP-p70s6K.

PMID- 11341788
TI  - Antitumor and antiangiogenic effects of somatostatin receptor-targeted in situ
      radiation with (111)In-DTPA-JIC 2DL.
AB  - INTRODUCTION: Expression of somatostatin receptor subtype 2 (sst 2) in angiogenic
      tumor vessels appears to be homogeneous, while tumor cell expression of this
      receptor is often heterogeneous. We have developed a novel in vitro three
      dimensional tumor angiogenesis model to study the antitumor and the
      antiangiogenic effects of radiolabeled somatostatin analogs. We hypothesized that
      targeted in situ radiation with an Auger electron-emitting radiolabeled
      somatostatin analog would produce receptor-specific cytotoxicity in sst 2
      expressing cells. MATERIALS AND METHODS: IMR-32 human neuroblastoma (sst 2
      positive) and MDA MB-231 human breast cancer (sst 2-negative) xenografts were
      created in nude mice from monolayer cell cultures. Fragments of these tumors were
      embedded in three-dimensional fibrin gels supplemented with endothelial growth
      media and incubated for a period of 14 days. Tumor fragments were treated with 50
      microCi/ml of (111)In-JIC 2DL, a sst 2-preferring somatostatin analog, or medium
      on Day 1. Initial angiogenic activity was determined at 48 h and the mean
      angiogenic score and tumoricidal responses were assessed on Day 14. RESULTS AND
      CONCLUSION: Tumoricidal effects of (111)In-JIC 2DL were seen only in sst 2
      positive IMR-32 tumors. However, the angiogenic response was inhibited in both
      IMR-32 and MDA MB-231 tumors independent of the tumor cells' sst 2 status.
      Somatostatin receptor-mediated in situ radiation therapy has profound cytotoxic
      effects on angiogenic blood vessels and sst 2-expressing tumor cells.

PMID- 11341789
TI  - A dedicated craniofacial trauma team improves efficiency and reduces cost.
AB  - BACKGROUND: In this era of limited medical resources there is ever increasing
      pressure to lower costs, while preserving high-quality patient care. A dedicated
      craniofacial and skull base trauma team (SBT) was established at our Level I
      trauma center in July 1998. Previously, a rotating call panel of multiple private
      surgical subspecialists consulted on trauma patients with craniofacial or skull
      base injuries (Pre-SBT). This study was designed to assess the impact a dedicated
      craniofacial and skull base trauma team has on the cost and quality of patient
      care. MATERIALS AND METHODS: A retrospective review of the trauma registry and
      charts was performed including all craniofacial and skull base trauma cases in
      the 18 months Pre-SBT and 18 months following the establishment of a SBT.
      RESULTS: During the Pre-SBT period there were 29 craniofacial and skull base
      operations, whereas 28 such cases were performed by the SBT. The age, sex, injury
      severity score (ISS), mechanism of injury, and type of craniofacial/skull base
      injuries were comparable between groups. The SBT group demonstrated a reduction
      in the number of patients transferred to other institutions for definitive care
      (7 vs 1, P = 0.05) and statistically significant reduction in the number of
      subspecialty consultations (2.4 vs 1.3), time to operation (7.5 vs 3.0 days), and
      length of hospitalization (11.8 vs 6.8, all with P <or= 0.001). Additionally,
      hospital charges were markedly reduced in the SBT group (106,424 dollars vs
      58,136 dollars, P < 0.01). CONCLUSIONS: The addition of a dedicated craniofacial
      trauma team to a Level I trauma center provides more comprehensive care, improves
      efficiency, and reduces cost.

PMID- 11341790
TI  - Protein kinase C inhibition abrogates hepatic ischemic preconditioning responses.
AB  - INTRODUCTION: A transient period of warm ischemia prior to a longer ischemic
      episode (ischemic preconditioning) protects the hepatic graft from cold ischemia.
      The mechanism for this protection is unknown, as is the role of protein kinase C
      in ischemic preconditioning responses. METHODS: Livers from 40 kg Yorkshire pigs
      were harvested and subjected to 2 h of cold ischemia (n = 6) (control). Another
      group of harvested livers was pretreated with a 15-min ischemic period followed
      by 15 min of in situ perfusion with (n = 5) or without (n = 5) a protein kinase C
      inhibitor, chelerythrine. Following cold ischemia, all grafts were reperfused on
      a perfusion circuit and the following variables evaluated: (1) hepatic graft
      function, (2) graft circulatory impairment, (3) hepatocellular damage, and (4)
      endothelial cell damage. Protein kinase C levels were also evaluated by Western
      blot in the cytoplasm of all grafts. RESULTS AND DISCUSSION: Ischemic
      preconditioned grafts demonstrate improved graft function, reduced graft
      circulatory impairment, and reduced endothelial cell damage as compared to cold
      ischemia controls. When preconditioned grafts were pretreated with chelerythrine,
      graft function, graft circulatory impairment, and endothelial cell damage were no
      different than cold ischemia controls. Ischemic preconditioned grafts
      demonstrated decreased levels of protein kinase C prior to cold ischemia. There
      was no change in protein kinase C levels in cold ischemia controls or
      chelerythrine-pretreated grafts prior to cold ischemia. These data indicate that
      modulation of protein kinase C is essential for ischemic preconditioning
      responses in the cold preserved hepatic graft.

PMID- 11341791
TI  - Inducible nitric oxide synthase mediates gut ischemia/reperfusion-induced ileus
      only after severe insults.
AB  - Inducible nitric oxide synthase (NOS 2) is thought to play a role in gut motility
      disorders that occur under proinflammatory conditions. Clinically, ileus occurs
      after sepsis and shock-induced gut ischemia/reperfusion (I/R). The purpose of
      this study was to determine if NOS 2 mediates impaired intestinal transit in well
      established models of both moderate and severe gut ischemia/reperfusion. At
      laparotomy, Sprague-Dawley rats had duodenal catheters placed. Small intestinal
      transit was determined by quantitating the percentage tracer (FITC-dextran) in 10
      equal segments of intestine 30 min after catheter injection [expressed as the
      mean geometric center (MGC) of distribution]. Transit was assessed at 6 and 24 h
      after gut ischemia [45 or 75 min of superior mesenteric artery occlusion (SMAO)
      with sham laparotomy as control]. In a separate set of experiments, N(6)
      (iminoethyl)-L-lysine (L-NIL), a selective NOS 2 antagonist, was administered 1 h
      prior to laparotomy and transit was determined after 6 h as described above.
      Ileal NOS 2 expression was assessed by Western immunoblot and quantitative "real
      time" RT-PCR. We observed that both 45 and 75 min of SMAO decreased intestinal
      transit at 6 h of reperfusion compared to sham. Ileal NOS 2 mRNA and protein were
      increased after 75, but not 45, min of SMAO. In addition, L-NIL improved transit
      after 75, but not 45, min of SMAO. We conclude that (1) NOS 2 is upregulated in
      the gut only after more severe ischemic insults, and (2) ileus is mediated, at
      least in part, by NOS 2 under these conditions.

PMID- 11341792
TI  - Modified AdCTLA-4 vector blocks alloimmune response in vitro.
AB  - BACKGROUND: Gene transfer of the costimulatory blockade molecule CTLA-4Ig into
      cold-preserved rat liver allografts results in indefinite allograft survival.
      Despite local delivery, this mode of immunomodulation is associated with systemic
      immunosuppression. In an effort to restrict immunosuppression to the graft, we
      have constructed a novel adenoviral vector, AdCTLA-4ex-TAG, in which the Ig
      sequence of CTLA-4Ig DNA has been deleted to destabilize the gene product to
      promote rapid extrahepatic degradation while maintaining its immunosuppressive
      activity within the graft milieu. METHODS: (1) Vector construction. CTLA-4
      extracellular binding domain (CTLA-4ex) was prepared by PCR-based cloning methods
      and fused in frame to a genetic element encoding an epitope TAG allowing
      identification of the transgene product CTLA-4exTAG. CTLA-4exTAG was subcloned
      into a shuttle vector enabling isolation of AdCTLA-4exTAG. (2) In vitro
      transfection: AdCTLA-4exTAG was transfected into MH(1)C(1) cells and then
      supernatant was recovered for Western blot analysis. (3) In vitro alloimmune
      response was characterized by CFSE proliferation assay. (4) Extrahepatic effect
      of AdCTLA-4exTAG was characterized by the ability to control tumor growth after
      implantation of a regressive, immune sensitive cancer cell line (REGb) in the
      skin of BDIX rats after liver transduction with AdCTLA-4exTAG. RESULTS:
      Expression and secretion of the recombinant protein were documented by Western
      blot after infection of the MH(1)C(1) cell line() with AdCTLA-4exTAG. Addition of
      infected MH(1)C(1) cell supernatant resulted in abrogation of alloimmune response
      as shown by markedly diminished division of CD4(+) T cells in a CFSE
      proliferation assay. Extrahepatic tumor regressed normally after liver
      transduction with AdCTLA-4exTAG. CONCLUSIONS: These results show efficient in
      vitro expression of CTLA-4exTAG after transfection with AdCTLA-4exTAG. The
      modified protein retains its ability to abrogate in vitro alloimmune response.
      Efficient control of extrahepatic tumor growth after liver-directed delivery of
      AdCTLA-4exTAG suggests that the immunosuppressive effect of this vector is
      restricted to the liver. These results set the ground for the utilization of this
      novel adenoviral vector in the transplant setting.

PMID- 11341793
TI  - Oxygen dilation in fetal pulmonary arterioles: role of K(+) channels.
AB  - BACKGROUND: Oxygen is a potent stimulus for pulmonary vasodilation. Potassium
      channels have been implicated as both sensors and effectors for oxygen-induced
      changes in pulmonary vascular tone. We have examined the effect of potassium
      channel blockers on oxygen-induced vasodilation in isolated pulmonary arterioles
      from fetal rats at term. MATERIALS AND METHODS: Third generation pulmonary
      arterioles were isolated from fetal rats on Day 22 of gestation, cannulated,
      pressurized at constant distending pressures, and preconstricted by suffusion
      with a salt solution bubbled with a "hypoxic gas" mixture (pO(2) <or=50 mm Hg).
      Oxygen-induced vasodilation was measured as percentage reversal of the "hypoxic"
      vasoconstriction after 30 min of suffusion with "normoxic" solution (pO(2) 90-145
      mm Hg). Responses were recorded in the absence of blockers (controls) or in the
      presence of a voltage-gated K(+) channel (K(v)) blocker, 4-aminopyridine; an ATP
      sensitive K(+) channel (K(ATP)) blocker, glibenclamide; a Ca(2+)-activated K(+)
      channel (K(Ca)) blocker, charybdotoxin; or a nonspecific K(+) channel blocker,
      tetraethylammonium. RESULTS: In control arterioles, normoxic suffusion for 30 min
      reversed hypoxic preconstriction by 83 +/- 19%. 4-aminopyridine significantly
      attenuated (44 +/- 9%), and glibenclamide and charybdotoxin had no effect (80 +/-
      16 and 79 +/- 20%) on the magnitude of normoxic vasodilation. CONCLUSIONS: Our
      results are consistent with a contribution of K(v) channels, but not K(ATP) or
      K(Ca) channels, to oxygen-induced vasodilation in third generation pulmonary
      arterioles from term fetal rats.

PMID- 11341795
TI  - Do medical school surgical rotations influence subspecialty choice?
AB  - BACKGROUND: A comprehensive exposure to general surgery is essential for medical
      students pursuing careers in surgery. Occasionally, students applying for
      surgical residency positions must choose a subspecialty field prior to starting
      their residency training. Often, this decision is heavily based on their
      experience on various surgical clerkships. MATERIALS AND METHODS: To determine if
      surgical clerkships influence subspecialty choice, we surveyed medical students
      who interviewed for general surgery training over a 2-year period at The Johns
      Hopkins Hospital. RESULTS: Of 211 surveys sent, 146 were returned (66%). The mean
      age of the students was 26 +/- 0 years with 21% being female. Students
      anticipating subspecialization in cardiothoracic, plastic, pediatric, and
      transplant surgery saw significantly more operations in their respective fields.
      Similar trends were seen in vascular surgery and surgical oncology. Despite the
      apparent differences in exposure to subspecialty operations, all students saw
      equal numbers of hernia repairs and laparoscopic cholecystectomies. CONCLUSIONS:
      While medical students pursuing careers in surgery have equal exposure to general
      surgery, their anticipated subspecialty field highly correlated with their
      operative exposure to that field. Thus, medical school surgical rotations appear
      to highly influence subspecialty choice.

PMID- 11341794
TI  - Laparoscopic repair of traumatic diaphragmatic injuries.
AB  - BACKGROUND: Laparoscopy has been proposed as a diagnostic and potentially
      therapeutic modality for penetrating diaphragmatic lacerations. The purpose of
      this study was to assess the technical feasibility and strength of various
      laparoscopic repairs of diaphragmatic injuries. METHODS: Swine underwent either
      open suture repair or laparoscopic repair by staple, suture, or patch technique
      of a 2-cm laceration to both the right and the left muscular or tendinous
      diaphragmatic leaflets. Six weeks after operation, diaphragms were harvested for
      either histologic analysis or bursting strength measurements. RESULTS: All
      methods of repair proved technically feasible. There was no significant
      difference in bursting strength measurements between treatment groups. Bursting
      was due to tissue failure either at or adjacent to the repair site. Histologic
      analysis confirmed healing of all specimens with the laparoscopic patch technique
      inciting less inflammation and greater fibroblastic proliferation than the other
      techniques. CONCLUSIONS: Laparoscopic repair of diaphragmatic lacerations can be
      accomplished using any of the currently available techniques. Laparoscopic
      stapling, suturing, or patch techniques all result in complete healing with a
      strong and durable repair. When selecting a particular technique, familiarity of
      the surgeon should be used as a guideline.

PMID- 11341796
TI  - Assessment of knowledge of melanoma risk factors, prevention, and detection
      principles in Texas teenagers.
AB  - INTRODUCTION: The incidence of melanoma has increased in the past 10 years more
      rapidly than any other cancer. Exposure to intense solar radiation in youth
      significantly increases the lifetime risk of developing melanoma. We postulate
      that teenagers have little awareness of melanoma prevention or detection
      principles. The purpose of this study was to assess the knowledge of teenagers
      about melanoma and to identify which age groups are most receptive to altering
      their sun exposure behaviors. METHODS: Two hundred and ten examinations testing
      general knowledge of sun exposure and melanoma were completed and returned by
      junior high and high school students ages 12 to 18 in Dallas and Houston, Texas.
      All students completing and returning the examination were provided with the
      correct answers to the test and a detailed explanation of each of the test items
      as part of an educational exercise. A second questionnaire was then administered
      to determine the effect of the educational exercise on future sun exposure
      practices. Students were divided into two age groups (12 to 15 and >or=16 years
      old) for comparison of scores on the knowledge examination and responses to
      behavioral items. Comparison of response rates between age groups was performed
      using chi(2) analysis. RESULTS: The return rate was 100%, with 109 students age
      12-15 years, and 101 students >or=16 years. Seventy-six percent of all
      respondents sunbathed outdoors, and 18% had used a tanning bed in the past 6
      months. Thirty-three percent of students admitted to at least three blistering
      sunburns in the past. The average score on the knowledge assessment examination
      was 65% correct for students >or=16 years old and 54% correct for those 12-15
      years old. Students 12 to 15 years old were significantly more likely to indicate
      they planned to change future behaviors regarding performance of skin self
      examinations and limiting sun exposure as compared to the older students.
      CONCLUSION: A significant number of teenagers have already enhanced their risk
      for future melanoma by suffering severe sunburns. Students younger than 16 years
      of age were significantly more likely to indicate they planned to change future
      behaviors after receiving information about melanoma. The data from this pilot
      study support education aimed at younger age groups to most effectively achieve
      risk reduction and prevent future melanomas.

PMID- 11341797
TI  - Human T-cell-porcine endothelial cell interactions induce human Th1 cytokines and
      porcine activation markers.
AB  - BACKGROUND: Since the future of clinical transplantation will undoubtedly include
      xenotransplantation, there is a need to examine human anti-pig cellular
      reactions. The objective of this study is to use human anti-porcine mixed
      lymphocyte endothelial cell culture (MLEC) to investigate cell interactions,
      cross-species molecular compatibilities, and the induction of human cytokines and
      porcine activation markers. METHODS: Human peripheral blood mononuclear cells or
      enriched CD4+ T cells depleted of professional antigen-presenting cells were
      cultured with resting pig aortic endothelial cells in the absence of exogenous
      cytokines. T-cell proliferative responses were measured and PAEC were monitored
      for cell surface markers by flow cytometry. Culture supernatants were assayed for
      human TNF-alpha and IFN-gamma by ELISA. RESULTS: Human T cells proliferated
      strongly in response to PAEC (median stimulation index = 75), even in serum-free
      cultures. High levels of the human Th1 cytokines TNF-alpha (20-350 pg/ml) and IFN
      gamma (200-3800 pg/ml) were detected only in cultures containing PAEC, with
      levels peaking on Day 4. CD4+ T-cell-enriched, APC-depleted responders maintained
      proliferative anti-PAEC responses and cytokine release. By Day 3, MHC Class II
      and VCAM expression was induced in 92-96% PAEC: mean fluorescence intensity (MFI)
      increased from 5 to 83 +/- 12 and 166 +/- 74, respectively, and MHC Class I was
      increased from MFI 31 to 965 +/- 269. CONCLUSIONS: These results indicate that
      MLEC is an excellent in vitro model in which to study human anti-porcine cellular
      responses. Human T cells are activated in response to direct antigen presentation
      by PAEC, which are also activated in this system. Specific cytokines, receptors,
      and adhesion molecules appear to cross the xenograft barrier and play a critical
      role in T-cell - PAEC interactions. Such interactions are likely to affect VEC
      activation and immune responses to porcine xenografts in vivo.

PMID- 11341798
TI  - Novel effect of leptin on small intestine adaptation.
AB  - BACKGROUND: Leptin is a 16-kDa peptide produced by adipocytes that plays an
      important role in the regulation of body fat and satiety. We have previously
      shown that leptin is a growth factor for normal rat small intestine. This study
      was designed to examine the effect of systemic leptin administration on small
      bowel absorptive function after massive small bowel resection (MSBR). MATERIALS
      AND METHODS: Twenty-one adult male Sprague-Dawley rats underwent an 80% small
      bowel resection and end-to-end jejunoileal anastomosis. Seven days following
      resection, all rats had placement of a jugular venous catheter connected to a
      subcutaneously placed osmotic minipump and were divided into three groups based
      on the content of each minipump: Group 1 (n = 7) 0.1% bovine serum albumin; Group
      2 (n = 7) leptin 2 microg/kg/day; and Group 3 (n = 7) leptin 4 microg/kg/day.
      Following a 14-day infusion period, [(14)C]galactose absorption was measured
      using a closed-recirculation technique. Mucosal DNA content was determined for
      all groups using a standard DNA purification kit. Mucosal RNA was extracted and
      RT-PCR was performed using the following primers: sodium/glucose cotransporter
      (SGLT-1), fructose transporter (GLUT-5), and glyceraldehyde-3-phosphate
      dehydrogenase, an internal standard. PCR products were separated on a 4% agarose
      gel and relative band intensities were measured. Statistical analysis was
      performed using ANOVA and expressed as means +/- SEM. RESULTS: Group 2 showed a
      44% increase in galactose absorption (P < 0.01) and a 14% increase in GLUT-5 band
      intensity (P < 0.05), but no change in DNA content or SGLT band intensity.
      CONCLUSIONS: This study demonstrates for the first time that leptin enhances
      small intestine carbohydrate absorption beyond the normal adaptive response
      following MSBR. Leptin may be clinically useful in patients with inadequate
      intestinal function.

PMID- 11341799
TI  - Dehydroepiandrosterone restores hepatocellular function and prevents liver damage
      in estrogen-deficient females following trauma and hemorrhage.
AB  - INTRODUCTION: Recent studies have shown that administration of the sex steroid
      dehydroepiandrosterone (DHEA) in males following trauma-hemorrhagic shock has
      salutary effects on the depressed cardiovascular and immunological functions
      under those conditions. Since the effects of sex steroids are gender specific, we
      examined whether administration of DHEA has any beneficial effects on
      hepatocellular function in female rats with low estrogen levels following trauma
      hemorrhage. METHODS: Ovariectomy was performed in female Sprague-Dawley rats 14
      days prior to the experiments. The animals then underwent a 5-cm midline
      laparotomy and were subjected to hemorrhagic shock (40 mm Hg for 90 min). This
      was followed by fluid resuscitation (Ringer's lactate over 60 min) and
      administration of DHEA (30 mg/kg BW) or vehicle subcutaneously at the end of
      resuscitation. At 24 h after resuscitation hepatocellular function, i.e.,
      clearance of indocyanine green (ICG), and hepatocyte damage (serum alanine
      aminotransferase) were measured. Plasma levels of DHEA and 17beta-estradiol were
      also assayed. RESULTS: Vehicle-treated rats had significantly reduced
      hepatocellular function, increased ALT activity, and decreased levels of 17beta
      estradiol following trauma-hemorrhage compared to sham-operated animals (P <
      0.05, ANOVA and Student-Newman-Keuls test). In animals receiving DHEA following
      trauma-hemorrhage, hepatocellular function and ALT activity were similar to those
      of shams. However, administration of DHEA did not influence the plasma levels of
      17beta-estradiol. CONCLUSIONS: Administration of DHEA following trauma-hemorrhage
      restored hepatocellular function and reduced hepatic damage that was observed in
      ovariectomized female rats under such conditions. This salutary effect of DHEA
      did not appear to be due to elevated levels of plasma 17beta-estradiol. We
      therefore propose that DHEA should be considered a novel, safe, and useful
      adjunct in the treatment of trauma-induced hepatocellular dysfunction in
      ovariectomized and postmenopausal females.

PMID- 11341800
TI  - Why nuclear ribosomal DNA spacers (ITS) tell different stories in Quercus.
AB  - The molecular systematics of Quercus (Fagaceae) was recently assessed by two
      teams using independently generated ITS sequences. Although the results disagreed
      in several remarkable features, the phylogenetic trees for either hypothesis were
      highly supported by bootstrap resampling. We have reanalyzed the ITS sequences
      used by both teams (eight taxa) to reveal the underlying patterns of this
      divergence. Within species, conspicuous length and G + C% divergence were evident
      in most sequence comparisons. In addition, a high rate of substitutions and
      deletions involving highly conserved motifs in both ITS spacers were present in a
      set of sequences. This was coupled with a less thermodynamic stability in the RNA
      structure, lacking conserved hairpins that are putatively involved in the
      processing of the RNA transcripts. Compelling evidence suggests that the
      divergent ITS alleles reported by one team are pseudogenes, i.e., nonfunctional
      paralogous loci. The hypothesis that the contrasting phylogenetic histories drawn
      from Quercus using ITS data are not strictly related to technical differences
      between laboratories, but that they have rather been generated from the analysis
      of paralogous sequences, best reconciles the available data. The risk of
      incorporating ITS paralogues in plant evolutionary studies which can distortion
      the phylogenetic signal should caution molecular systematists. Without a detailed
      inspection of some basic features of the sequence, including the integrity of the
      conserved motifs and the thermodynamic stability of the secondary structures of
      the RNA transcripts, errors in evolutionary inferences could be easily
      overlooked.

PMID- 11341801
TI  - Evolution of Lycopodiaceae (Lycopsida): estimating divergence times from rbcL
      gene sequences by use of nonparametric rate smoothing.
AB  - By use of nonparametric rate smoothing and nucleotide sequences of the rbcL gene,
      divergence times in Lycopodiaceae are estimated. The results show that much
      extant species diversity in Lycopodiaceae stems from relatively recent cladogenic
      events. These results corroborate previous ideas based on paleobotanical and
      biogeographical data. Previous molecular phylogenetic analyses recognized a split
      into neotropical and paleotropical clades in Huperzia, which contains 85-90% of
      all living species. Connecting this biogeographical pattern with continent
      movements, the diversification of this epiphytic group was suggested to coincide
      with that of angiosperms in the mid to Late Cretaceous. Results presented here
      are consistent with this idea, and the diversification of the two clades is
      resolved as Late Cretacous (78 and 95 Myr). In the related genera Lycopodium and
      Lycopodiella, the patterns are somewhat different. Here species diversity is
      scattered among different subgeneric groups. Most of the high-diversity
      subgeneric groups seem to have diversified very recently (Late Tertiary), whereas
      the cladogenic events leading to these groups are much older (Early to Late
      Cretaceous). Our analysis shows that, although much living species diversity
      stems from relatively recent cladogenesis, the origins of the family (Early
      Carboniferous) and generic crown groups (Early Permian to Early Jurassic) are
      much more ancient events.

PMID- 11341802
TI  - Evolution of the mitochondrial DNA control region and cytochrome b genes and the
      inference of phylogenetic relationships in the avian genus Lophura (Galliformes).
AB  - The entire mitochondrial DNA control region (mtDNA CR) and cytochrome b (cyt b)
      genes were sequenced in 10 of the 11 extant species of gallopheasants (Lophura).
      The cyt b from L. diardi and L. ignita showed unusual leucine-coding codons at
      the expected terminal 3' end of the gene. Presence of conserved functional motifs
      in the inferred amino acid sequences, conserved secondary structures of the
      flanking tRNA(Pro) and tRNA(Thr), and Southern hybridization concordantly suggest
      that these cyt b represent functional mitochondrial genes and not nuclear
      transpositions. Functional stop codons can be generated by RNA editing of the
      primary transcripts from these sequences. Despite strong site and domain
      substitution rate heterogeneity, CR and cyt b diverged at similar rates, on
      average, and expressed congruent phylogenetic signals. Phylogenetic analyses of
      the concatenated sequences split Lophura into five clades including (1) L.
      bulweri, (2) L. diardi-L. ignita, (3) L. erythrophthalma-L. inornata, (4) L.
      leucomelanos-L. nycthemera, and (5) L. swinhoii-L. edwardsi-L. hatinhensis. Basal
      relationships among these clades, which include species distributed in
      continental South East Asia and the Sundaland archipelago, were weakly resolved,
      suggesting the occurrence of rapid cladogenic events in the early evolutionary
      history of Lophura. A conventional calibration of mtDNA sequence divergence
      indicates a mid to late Pliocene evolution of the main clades in Lophura, which
      could have diversified in allopatry in continental South East Asia. Sundaland
      could have been colonized lately and independently by the different clades.
      Consequently, cyclic changes in late Pleistocene climate and landscape might not
      have increased rates of speciation in genus Lophura in Sundaland.

PMID- 11341804
TI  - Molecular phylogeny of tubificid oligochaetes with special emphasis on Tubifex
      tubifex (Tubificidae).
AB  - Tubifex tubifex is a cosmopolitan freshwater oligochaete whose presence has been
      studied as a health indicator of the aquatic environment and as a host for
      several myxozoan parasites of fish. Unfortunately, current morphological criteria
      used to distinguish Tubifex spp. (Tubificidae) are inadequate. We therefore
      developed mitochondrial 16S ribosomal DNA markers to examine phylogenetic
      relationships among aquatic oligochaetes and to distinguish species of Tubifex
      that might serve as hosts for a particular myxozoan parasite, Myxobolus
      cerebralis. Our phylogenetic analyses of oligochaetes based on a 378-bp segment
      yielded one most parsimonious tree with three major groups that corresponded to
      the families Lumbricidae, Sparganophilidae, and Tubificidae. T. tubifex and T.
      ignotus formed a monophyletic assemblage, and a sister relationship between the
      genera Tubifex and Limnodrilus was strongly supported. A second analysis of the
      relationship within the genus Tubifex identified six genetically distinct
      lineages of T. tubifex from North America and Europe that were separated by
      genetic distances comparable to those found for "well-defined" species of
      Limnodrilus. Therefore, the existence of several morphologically
      indistinguishable, thus cryptic, species of Tubifex in North America and Europe
      is suggested.

PMID- 11341805
TI  - New clades of euthyneuran gastropods (Mollusca) from 28S rRNA sequences.
AB  - Recent morphological and molecular results on phylogeny of euthyneuran
      gastropods, which include opisthobranchs and pulmonates, have greatly diminished
      previous supposed resolution of their phylogenetic relationships. In addition to
      recent morphological results, sequences of the D1 and D2 domains of the 28S rRNA
      are here analyzed by parsimony for 31 euthyneuran species. The molecular and
      previous morphological data sets were not congruent according to an ILD test, and
      morphological and molecular data could not be analyzed simultaneously.
      Consequently Bremer's Combinable Component Consensus was used to obtain a new
      tree, with the following supported molecular results: monophyly of a new clade of
      opisthobranchs including actively swimming Euthyneura, i.e., pelagic Gymnosomata
      and Thecosomata plus benthic Anaspidea; first molecular confirmation of
      monophylies of Hygrophila, including Chilina, Acteonoidea, and Sacoglossa, which
      include both shell-bearing species and slugs; and new confirmation of the
      monophyly of Stylommatophora. Morphological characters which support the new
      clades obtained here are discussed.

PMID- 11341803
TI  - Phylogenetic analysis of partial sequences of elongation factor 1alpha identifies
      major groups of lice (Insecta: Phthiraptera).
AB  - As a first attempt to use molecular data to resolve the relationships between the
      four suborders of lice and within the suborder Ischnocera, we sequenced a 347-bp
      fragment of the elongation factor 1alpha gene of 127 lice (Insecta: Phthiraptera)
      as well as outgroup taxa from the order Psocoptera. A number of well-supported
      monophyletic groups were found but the relationships among many of these groups
      could not be resolved. While it is probable that multiple substitutions at high
      divergences and ancient radiation over a short period of time have contributed to
      the problem, we attribute most of this lack of resolution to the high ratio of
      taxa to characters. Nevertheless, the sequence data unequivocally support a
      number of important relationships that are at variance with the conclusions of
      morphological taxonomy. These include the sister group relationship of
      Chelopistes and Oxylipeurus, two lice occupying different ecological niches on
      the same host, which have previously been assigned to different families. These
      results provide evidence in support of the hypothesis that lice have speciated in
      situ on the host in response to niche specialization and that this has given rise
      to convergent morphologies in the lice of different host groups which share
      similar ecological niches. We discuss our attempts to overcome the limitations of
      this large data set, including the use of leaf stability analysis, a new method
      for analyzing the stability of taxa in a phylogenetic tree, and examine a number
      of hypotheses of relationships based on both traditional taxonomy and host
      associations.

PMID- 11341806
TI  - Molecular phylogeny of Eastern Pacific porcelain crabs, genera Petrolisthes and
      Pachycheles, based on the mtDNA 16S rDNA sequence: phylogeographic and systematic
      implications.
AB  - Porcelain crabs, genera Petrolisthes and Pachycheles, are diverse and abundant
      members of the eastern Pacific near-shore decapod crustacean community.
      Morphology-based taxonomic analyses of these crabs have determined groupings of
      affiliated species, but phylogenetic relationships remain unknown. We used
      sequence data from the mitochondrial 16S rRNA gene of 46 species of eastern
      Pacific porcelain crabs to perform phylogenetic analyses by distance and
      parsimony methods. Our results are used to compare the taxonomic significance of
      morphological and molecular characters, to examine sequence divergence rates of
      crab 16S rRNA genes, and to analyze the phylogeographic history of these crabs.
      Our phylogenetic trees indicate that the genus Petrolisthes is divided into two
      main clades, reflecting morphological features. One clade contains primarily
      tropical species, and the other contains species from throughout the eastern
      Pacific, as well as species in the genera Allopetrolisthes and Liopetrolisthes.
      Phylogenetic trees of Pachycheles suggest an antitropical distribution; north and
      south temperate species form one clade and tropical species form a second clade.
      Sequence divergence rates of the 16S rRNA gene from three pairs of geminate
      species can be used to date divergence times, and we discuss porcelain crab
      phylogeographic patterns in relation to paleogeographic events.

PMID- 11341807
TI  - Phylogeny and biogeography of the genus Lycium (Solanaceae): inferences from
      chloroplast DNA sequences.
AB  - Lycium comprises approximately 70 species and is disjunctly distributed in
      temperate to subtropical regions in South America, North America, southern
      Africa, Eurasia, and Australia. Among them, only Lycium sandwicense A. Gray
      sporadically occurs widely on oceanic islands in the Pacific Ocean. To
      investigate phylogenetic and biogeographic relationships of the genus with
      emphasis on L. sandwicense, the coding region of matK, the two intergenic spacers
      trnT (UGU)-trnL (UAA) and trnL (UAA)-trnF (GAA), and the trnL (UAA) intron of
      chloroplast DNA (cpDNA) were sequenced. A strict consensus tree resulting from
      the phylogenetic analysis indicates the following: (1) New World species comprise
      a potentially paraphyletic assemblage; (2) southern African, Australian, and
      Eurasian species together are monophyletic; (3) southern African species are a
      paraphyletic assemblage; and (4) L. sandwicense is in a clade with certain New
      World species. The estimated biogeographic events based on the cpDNA analysis
      indicate that (1) Lycium originated in the New World, (2) all southern African,
      Australian, and Eurasian species have a common ancestor from the New World, (3)
      Australian and Eurasian species originated once from a southern African
      progenitor, and (4) L. sandwicense differentiated from the New World species.

PMID- 11341808
TI  - Relationships among "ancient araliads" and their significance for the systematics
      of Apiales.
AB  - The relationship between the angiosperm families Apiaceae and Araliaceae (order
      Apiales) has been difficult to resolve, due in large part to problems associated
      with taxa characterized by a mixture of features typical of both families. Among
      such confounding groups are the araliads Delarbrea, Pseudosciadium, Myodocarpus,
      Mackinlaya, and Apiopetalum and many members of Apiaceae subfamily
      Hydrocotyloideae. Traditional systems have often envisioned these taxa as
      phyletic intermediates or bridges between the two families. To reevaluate the
      phylogenetic position of the "intermediate" araliad genera, molecular data were
      collected from nuclear (rDNA ITS) and plastid (matK) sequences from a complete or
      near-complete sampling of species in each genus. When analyzed with samples
      representing the other major clades now recognized within Apiales, results
      confirm and expand the findings of previously published studies. The five araliad
      "intermediates" are placed within two well-supported clades clearly segregated
      from the "core" groups of both Apiaceae and Araliaceae. These segregate clades
      closely parallel traditional definitions of the araliad tribes Myodocarpeae
      (Delarbrea, Pseudosciadium, and Myodocarpus) and Mackinlayeae (Mackinlaya and
      Apiopetalum), and relationships among the species within these clades are largely
      supported by morphological and anatomical data. Based on these results,
      Myodocarpeae and Mackinlayeae may best be treated as distinct families. This
      approach would render four monophyletic groups within Apiales, to which a fifth,
      Pittosporaceae, cannot at present be excluded. Sampling of taxa from
      Hydrocotyloideae remains preliminary, but results confirm previous studies
      indicating the polyphyly of this subfamily: hydrocotyloid taxa may be found in no
      fewer than three major clades in Apiales.

PMID- 11341809
TI  - Phylogeny of Limia (Teleostei: Poeciliidae) based on NADH dehydrogenase subunit 2
      sequences.
AB  - Complete sequences for the mitochondrial gene NADH Dehydrogenase 2 (ND2) and
      partial sequences for the tRNA-Met and tRNA-Trp genes were obtained for 11
      populations of the poeciliid fish genus (or subgenus) Limia, including species
      from Hispaniola, Cuba, Jamaica, and Grand Cayman Islands. Additional sequences
      for Limia (2 species), Pamphorichthys (3), Poecilia (16), and Xiphophorus (1),
      all from the tribe Poeciliini, were extracted from GenBank, as was a sequence for
      Heterandria formosa, from the tribe Heterandriini. Phylogenetic analyses included
      parsimony, distance methods, and maximum-likelihood. Several Limia species groups
      that had been proposed based on morphological data were evaluated. The versicolor
      species group was strongly supported, as was the close relationship between the
      Cuban Limia vittata and the Grand Cayman Limia caymanensis. However, the proposed
      vittata species group was not upheld by the ND2 data. The phylogenetic position
      of Limia melanogaster, from Jamaica, was either sister to the versicolor species
      group or basal to all other included Limia species. Limia was found to be
      monophyletic; however, Limia species from the island of Hispaniola were not
      monophyletic. There was little support for any proposed sister group to Limia.
      The phylogeny was used to reconsider a previous comparative study of poeciliid
      courtship behavior and sexual dimorphism. The data indicated that there may have
      been two independent appearances of courtship display behavior in Limia;
      considering the tribe Poeciliini as a whole, there is evidence for as many as
      five appearances of display (including two within Limia), or a complex pattern of
      gains and losses of such behavior. The application of phylogenetic information to
      the comparative study did not refute the previously hypothesized correlation
      between the presence of a courtship display and the presence of sexual dimorphism
      in poeciliid fish.

PMID- 11341810
TI  - Phylogeny of rodentia (Mammalia) inferred from the nuclear-encoded gene IRBP.
AB  - The order Rodentia includes nearly half of all living mammalian species.
      Phylogenetic relationships among 22 species of rodents were investigated by use
      of a 1.2-kb region from exon 1 of the single-copy nuclear gene IRBP. IRBP has
      been extensively used for study of interordinal phylogeny in mammals, which
      allowed inclusion of 50 outgroup species, representing every eutherian order plus
      seven marsupials. Several clades were strongly supported, regardless of
      analytical method or inclusion/exclusion of data. These include a monophyletic
      Muroidea, with a clade including Spalax and Rhizomys as the first divergence; a
      clade uniting Zapus with Dipus, but excluding Sicista; a monophyletic Myodonta
      (Muroidea plus Dipodidae); and a clade including Aplodontidae as sister to
      Sciuridae. One bipartition, separating Hystricognathi and Geomyoidea from the
      remaining rodents, is strongly supported in all analyses that include third
      position sites but almost completely absent from analyses that exclude third
      position sites. A combination of nonstationary nucleotide composition and branch
      length effects may be causing all methods examined (including those using the
      LogDet distance) to support an incorrect conclusion when third-position sites are
      analyzed together with first- and second-position sites.

PMID- 11341811
TI  - Pruned median networks: a technique for reducing the complexity of median
      networks.
AB  - Observations from molecular marker studies on recently diverged species indicate
      that substitution patterns in DNA sequences can often be complex and poorly
      described by tree-like bifurcating evolutionary models. These observations might
      result from processes of species diversification and/or processes of sequence
      evolution that are not tree-like. In these cases, bifurcating tree
      representations provide poor visualization of phylogenetic signals in sequence
      data. In this paper, we use median networks to study DNA sequence substitution
      patterns in plant nuclear and chloroplast markers. We describe how to prune
      median networks to obtain so called pruned median networks. These simpler
      networks may help to provide a useful framework for investigating the
      phylogenetic complexity of recently diverged taxa with hybrid origins.

PMID- 11341813
TI  - Mapping of resistance to vegetable polyphenols among Aedes taxa (Diptera,
      Culicidae) on a molecular phylogeny.
AB  - To recover some evolutionary aspects of the interaction between culicine larvae
      and dietary polyphenols of the vegetation surrounding mosquito breeding sites, we
      constructed a phylogeny of the most common French Aedes species, chosen as
      reference species. We also evaluated the differential resistance of these larval
      taxa to the polyphenols of leaf litter from the riparian vegetation used as a
      food source. Mitochondrial DNA sequence analysis was performed among 14 different
      taxa and ecotypes (Aedes aegypti, Ae. albopictus, Ae. cantans, Ae. caspius, Ae.
      cataphylla, Ae. cinereus, Ae. detritus, Ae. geniculatus, Ae. mariae, Ae.
      pullatus, Ae. punctor, Ae. rusticus, Ae. sticticus, and Ae. vexans) through
      direct sequencing of a 763-base segment of the cytochrome oxidase subunit I gene.
      Phylogenetic analysis, based on nucleotide and amino acid sequences, was
      conducted by means of parsimony and distance methods. The differential tolerance
      of larvae to vegetable leaf litter was comparatively tested by use of 10-month
      old alder leaf litter as an experimental standard. The absence of correlation
      between resistance to polyphenols and molecular phylogeny suggests that larval
      adaptation to polyphenol-rich vegetable breeding sites is a labile character. The
      acquisition of such resistance appears not to be ancestrally inherited, but
      rather to be a dynamic adaptation to the environment. Molecular data also support
      the classical morphological classification within the Aedes genus.

PMID- 11341812
TI  - Relationships of scincid lizards (Mabuya spp; Reptilia: Scincidae) from the Cape
      Verde islands based on mitochondrial and nuclear DNA sequences.
AB  - Partial DNA sequences from two mitochondrial (mt) and one nuclear gene
      (cytochrome b, 12S rRNA, and C-mos) were used to estimate the phylogenetic
      relationships among the six extant species of skinks endemic to the Cape Verde
      Archipelago. The species form a monophyletic unit, indicating a single
      colonization of the islands, probably from West Africa. Mabuya vaillanti and M.
      delalandii are sister taxa, as indicated by morphological characters. Mabuya
      fogoensis and M. stangeri are closely related, but the former is probably
      paraphyletic. Mabuya spinalis and M. salensis are also probably paraphyletic.
      Within species, samples from separate islands always form monophyletic groups.
      Some colonization events can be hypothesized, which are in line with the age of
      the islands. C-mos variation is concordant with the topology derived from mtDNA.

PMID- 11341814
TI  - Reevaluation of 16S ribosomal RNA variation in Bufo (Anura: Amphibia).

PMID- 11341815
TI  - Effects of Training Goals and Goal Orientation Traits on Multidimensional
      Training Outcomes and Performance Adaptability.
AB  - This research examined the effects of mastery vs. performance training goals and
      learning and performance goal orientation traits on multidimensional outcomes of
      training. Training outcomes included declarative knowledge, knowledge structure
      coherence, training performance, and self-efficacy. We also examined the unique
      impact of the training outcomes on performance adaptability by predicting
      generalization to a more difficult and complex version of the task. The
      experiment involved 60 trainees learning a complex computer simulation over 2
      days. The research model posited independent effects for training goals relative
      to goal orientation traits and independent contributions of training outcomes to
      the performance adaptability of trainees. The findings were consistent with the
      proposed model. In particular, self-efficacy and knowledge structure coherence
      made unique contributions to the prediction of performance adaptability after
      controlling for prior training performance and declarative knowledge.
      Implications and extensions are discussed. Copyright 2001 Academic Press. 

PMID- 11341816
TI  - The Assessment of Goal Commitment: A Measurement Model Meta-Analysis.
AB  - Goals are central to current treatments of work motivation, and goal commitment
      is a critical construct in understanding the relationship between goals and
      performance. Inconsistency in the measurement of goal commitment hindered early
      research in this area but the nine-item, self-report scale developed by
      Hollenbeck, Williams, and Klein (1989b), and derivatives of that scale, have
      become the most commonly used measures of goal commitment. Despite this
      convergence, a few authors, based on small sample studies, have raised questions
      about the dimensionality of this measure. To address the conflicting
      recommendations in the literature regarding what items to use in assessing goal
      commitment, the current study combines the results of 17 independent samples and
      2918 subjects to provide a more conclusive assessment by combining meta-analytic
      and multisample confirmatory factor analytic techniques. This effort reflects the
      first combined use of these techniques to test a measurement model and allowed
      for the creation of a database substantially larger than that of previously
      factor analyzed samples containing these scale items. By mitigating sampling
      error, the results clarified a number of debated issues that have arisen out of
      previous small sample factor analyses and revealed a five-item scale that is
      unidimensional and equivalent across measurement timing, goal origin, and task
      complexity. It is recommended that this five-item scale be used in future
      research assessing goal commitment. Copyright 2001 Academic Press. 

PMID- 11341817
TI  - Gain-Loss Framing and Choice: Separating Outcome Formulations from Descriptor
      Formulations.
AB  - This article reexamines the assumptions underlying the disease problem used by
      Tversky and Kahneman (1981) to illustrate gain-loss formulation effects. It is
      argued that their reported effect may have been due to asymmetries in the
      ambiguity of the sure and risky prospects and to the entanglement of two distinct
      types of formulation manipulations: one having to do with the expected outcomes
      that are made explicit (positive vs negative) and the other having to do with the
      descriptors used to convey the relevant expected outcomes (lives saved/not saved
      vs lives lost/not lost). Two experiments using a formally equivalent problem in
      which these confounds were eliminated revealed no significant predictive effect
      of either descriptor or outcomes frames on choice, although a marginally
      significant framing effect was obtained in Experiment 1 when the signs of the two
      framing manipulations were congruent. Implications for prospect theory are
      discussed. Copyright 2001 Academic Press. 

PMID- 11341818
TI  - When Equal Chances = Good Chances: Verbal Probabilities and the Equiprobability
      Effect.
AB  - When six equally qualified candidates compete for the same position, p = 1/6 for
      each. People seem to accept this principle more readily for numerical than for
      verbal probabilities. Equal chances with three to six alternatives are often
      verbally described in a positive vein as "entirely possible" or "a good chance"
      and rarely negatively as "doubtful" or "improbable." This equiprobability effect
      of verbal probabilities is demonstrated in five studies describing job
      applicants, lottery players, competing athletes, and examination candidates. The
      equiprobability effect is consistent with a causal (propensity) view of
      probabilities, where chances are believed to reflect the relative strength of
      facilitating and preventive causes. If important conditions in support of the
      target outcome are present (the candidate is qualified for the position), and
      there is little to prevent it from occurring (no stronger candidates), chances
      appear to be good. In the presence of obstacles (one stronger candidate), or in
      the absence of facilitating conditions (the candidate is poorly qualified),
      chances appear to be poor, even when numerical p values remain constant. The
      findings indicate that verbal and numerical probability estimates can reflect
      different intuitions. Copyright 2001 Academic Press. 

PMID- 11341819
TI  - The Influence of Alternative Outcomes on Gut-Level Perceptions of Certainty.
AB  - Recent research has demonstrated that the perceived certainty of a focal outcome
      depends not only on the overall amount of evidence supporting the alternatives to
      the focal outcome, but also on how that evidence is distributed across those
      alternatives (e.g., Windschitl & Wells, 1998). Three experiments replicated this
      alternative-outcomes effect across a variety of evidence distributions and
      investigated a heuristic comparison account for the effect. Participants provided
      gut-level certainty estimates for winning hypothetical raffles in which they and
      several other players held specified numbers of tickets. Results revealed that
      alternative-outcomes effects are not dependent on variations in the rank-order
      status of the focal outcome (Experiment 1) and are reliable but reduced in
      magnitude when the focal outcome is the least likely outcome (Experiment 2).
      Also, consistent with a core premise of the heuristic comparison account,
      evidence supporting the strongest alternative outcome was shown to play the
      primary role in producing alternative-outcomes effects (Experiment 3). Copyright
      2001 Academic Press. 

PMID- 11341820
TI  - Bonus and Penalty in Common Pool Resource Dilemmas under Uncertainty.
AB  - Common pool resource (CPR) dilemmas constitute a class of social dilemmas in
      which equilibrium behavior results in Pareto deficient outcomes that are not at
      all desirable by the group. We focus on a class of CPR dilemmas that, in addition
      to strategic uncertainty about the harvesting behavior of the other group
      members, include environmental uncertainty about the size of the CPR. In an
      attempt to decrease the rate of requests from the common pool, and thereby
      increase individual payoffs, we extend previous research-both theoretically and
      experimentally-in two different directions. In the bonus treatment, a reward is
      given to the agent(s) who requests the least, and in the penalty treatment, a
      charge is imposed on the agent(s) who requests the most. We show that under
      equilibrium play the bonus treatment decreases total group request, whereas the
      penalty treatment increases it. Our experimental results do not support this
      prediction. Rather, both treatments considerably decrease the rate of request
      and, therefore, increase the rate of provision. The penalty treatment is shown to
      be more effective in reducing individual requests and enhancing provision rates
      than the bonus treatment. Copyright 2001 Academic Press. 

PMID- 11341821
TI  - The Role of Inferences in Sequential Bargaining with One-Sided Incomplete
      Information: Some Experimental Evidence.
AB  - Two experiments tested a sequential bargaining model with one-sided incomplete
      information and time discounting. The findings suggest that although the
      comparative statics of the normative model are somewhat descriptive of the
      qualitative features of the data, bargainers do not conform to the signaling
      process that underlies bargaining models with incomplete information. Rather than
      assess and refine a probabilistic assessment of the private information based on
      the informed bargainer's behavior, uninformed bargainers infer their opponents'
      competitiveness. Further, bargainers are unable to use cost of delay in the
      strategic manner dictated by the equilibrium solution. The evidence suggests that
      although bargaining behavior is primarily determined by situational constraints,
      bargainers attribute their opponents' behavior to personal disposition, such as
      their level of competitiveness. Copyright 2001 Academic Press. 

PMID- 11341822
TI  - ATP hydrolysis-coupled gating of CFTR chloride channels: structure and function.

PMID- 11341823
TI  - Crystallographic analysis of a novel complex of actinomycin D bound to the DNA
      decamer CGATCGATCG.
AB  - The potent anticancer drug actinomycin D (ActD) acts by binding to DNA, thereby
      interfering with replication and transcription. ActD inhibits RNA polymerase far
      more specifically than DNA polymerase. Such discrimination is not easily
      understood by the conventional DNA binding mode of ActD. We have solved and
      refined at 1.7 A resolution the crystal structure of ActD complexed to
      CGATCGATCG, which contains no canonical GpC binding sequence. The crystal data
      are space group P4(3)2(1)2, a = b = 47.01 A, and c = 160.37 A. The structure was
      solved by the multiple wavelength anomalous diffraction method using a 5-bromo-U
      DNA. The asymmetric unit of the unit cell contains two independent dimers of a
      novel slipped duplex complex consisting of two decamer DNA strands bound with two
      ActD drug molecules. (The DNA in one dimer is numbered C1 to G10 in one strand
      and C11 to G20 in the complementary strand and in the second dimer, C101 to G110
      and C111 to G120, respectively.) The structure reveals a highly unusual ActD
      binding mode in which the DNA adopts a slipped duplex with the A3-T4/A13-T14
      dinucleotides looped out. ActD intercalates between G2-C11* (C11* being from a
      symmetry-related molecule) and C5-G20 base pairs. Two such slipped duplex-ActD
      complexes bound to each other by mutually intercalating their T4/T14 bases into
      the helix cavities (located between C5-G20 and G6-C19 base pairs) of neighboring
      complexes, forming a dimer of drug-DNA complexes. The binding site mimics the
      drug binding at the elongation point during transcription. Modeling studies show
      that the ActD-DNA complex fits snugly in the active site cavity in RNA polymerase
      but not in DNA polymerase. This may explain the strong preference of ActD
      inhibition toward transcription.

PMID- 11341824
TI  - Role of the core region of the PufX protein in inhibition of reconstitution of
      the core light-harvesting complexes of Rhodobacter sphaeroides and Rhodobacter
      capsulatus.
AB  - PufX, the protein encoded by the pufX gene of Rhodobacter capsulatus and
      Rhodobacter sphaeroides, has been further characterized. The mature forms of
      these proteins contain 9 and 12 fewer amino acids, respectively, at the C
      terminal end of the protein than are encoded by their pufX genes. To identify the
      portion of PufX responsible for inhibition of LH1 formation in reconstitution
      experiments, different regions (N-terminus and several core regions containing
      different lengths of the C-terminus) of Rb. sphaeroides and Rb. capsulatus PufX
      were chemically synthesized. Neither the N- nor C-terminal polypeptides of Rb.
      sphaeroides were inhibitory to LH1 reconstitution. However, all core segments
      were active, causing 50% inhibition at a concentration ratio of between 3:1 and
      6:1 relative to the LH1 alpha-polypeptides whose concentrations were 3-4 microM.
      CD measurements indicated that the core segment containing 39 amino acids of Rb.
      sphaeroides PufX exhibited 47% alpha-helix in trifluoroethanol while the core
      segment containing 43 amino acids of Rb. capsulatus PufX exhibited 59 and 55%
      alpha-helix in trifluoroethanol and in 0.80% octylglucoside in water,
      respectively. Approximately 50% alpha-helix was also indicated by a PHD (Burkhard
      Rost) structure prediction. Binding of bacteriochlorophyll to these PufX core
      segments is implicated.

PMID- 11341825
TI  - Redox-dependent conformational selection in a Cys4Fe2S2 ferredoxin.
AB  - Putidaredoxin (Pdx), a Cys4Fe2S2 ferredoxin from Pseudomonas putida, exhibits
      redox-dependent binding to its physiological redox partner, cytochrome P450(cam)
      (CYP101), with the reduced form of Pdx (Pdx(r)) binding with greater affinity to
      oxidized camphor-bound CYP101 than the oxidized form, Pdx(o). It has been
      previously shown that Pdx(o) is more dynamic than Pdx(r) on all accessible time
      scales, and it has been proposed that Pdx(r) samples only a fraction of the
      conformational substates populated by Pdx(o) on a time average. It is postulated
      that the ensemble subset populated by Pdx(r) is the same subset that binds
      CYP101, providing a mechanism for coupling the Pdx oxidation state to binding
      affinity for CYP101. Evidence from a variety of sources, including redox
      dependent shifts of 15N and 13C resonances, indicates that the metal cluster
      binding loop of Pdx is the primary determinant of redox-dependent conformational
      selection. Patterns of paramagnetic effects suggest that the metal cluster
      binding loop contracts around the metal cluster upon reduction, possibly due to
      the strengthening of hydrogen bonds between the sulfur atoms of the metal cluster
      and the surrounding polypeptide NH and OH groups. Effects of this perturbation
      are then transmitted mechanically to other affected regions of the protein. A
      specific mutation has been introduced into the metal binding loop of Pdx, G40N,
      that slows conformational exchange sufficiently that the ensemble of
      conformational substates in Pdx(o) are directly observable as severe broadenings
      or splittings in affected NMR resonances. Many of the residues most affected by
      the mutation also show significant exchange contributions to 15N T(2) relaxation
      in wild-type Pdx(o). As predicted, G40N Pdx(r) shows a collapse of many of these
      multiplets and broadened lines to form much sharper resonances that are
      essentially identical to those observed in wild-type Pdx(r), indicating that
      Pdx(r) occupies fewer conformational substates than does Pdx(o). This is the
      first direct observation of such redox-dependent ensembles at slow exchange on
      the chemical shift time scale. These results confirm that conformational
      selection within the Fe2S2 cluster binding loop is the primary source of redox
      dependent changes in protein dynamics in Pdx.

PMID- 11341826
TI  - Alanine-scanning mutagenesis of the small-subunit beta A-beta B loop of
      chloroplast ribulose-1,5-bisphosphate carboxylase/oxygenase: substitution at Arg
      71 affects thermal stability and CO2/O2 specificity.
AB  - Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) enzymes from different
      species differ with respect to carboxylation catalytic efficiency and CO2/O2
      specificity, but the structural basis for these differences is not known. Whereas
      much is known about the chloroplast-encoded large subunit, which contains the
      alpha/beta-barrel active site, much less is known about the role of the nuclear
      encoded small subunit in Rubisco structure and function. In particular, a loop
      between beta-strands A and B contains 21 or more residues in plants and green
      algae, but only 10 residues in prokaryotes and nongreen algae. To determine the
      significance of these additional residues, a mutant of the green alga
      Chlamydomonas reinhardtii, which lacks both small-subunit genes, was used as a
      host for transformation with directed-mutant genes. Although previous studies had
      indicated that the betaA-betaB loop was essential for holoenzyme assembly, Ala
      substitutions at residues conserved among land plants and algae (Arg-59, Tyr-67,
      Tyr-68, Asp-69, and Arg-71) failed to block assembly or eliminate function. Only
      the Arg-71 --> Ala substitution causes a substantial decrease in holoenzyme
      thermal stability. Tyr-68 --> Ala and Asp-69 --> Ala enzymes have lower K(m)(CO2)
      values, but these improvements are offset by decreases in carboxylation V(max)
      values. The Arg-71 --> Ala enzyme has a decreased carboxylation V(max) and
      increased K(m)(CO2) and K(m)(O2) values, which account for an observed 8%
      decrease in CO2/O2 specificity. Despite the fact that Arg-71 is more than 20 A
      from the large-subunit active site, it is apparent that the small-subunit betaA
      betaB loop region can influence catalytic efficiency and CO2/O2 specificity.

PMID- 11341827
TI  - Influence of bulky polynuclear carcinogen lesions in a TATA promoter sequence on
      TATA binding protein-DNA complex formation.
AB  - The TATA binding protein (TBP) is an essential component of the transcription
      initiation complex that recognizes and binds to the minor groove of the TATA DNA
      duplex consensus sequences. The objective of this study was to determine the
      effect of a carcinogen-modified adenine residue, positioned site-specifically
      within a regulatory TATA DNA sequence, on the binding of TBP. Two 25-mer
      oligonucleotides with stereoisomeric 10S (+)-trans-anti- or 10R (-)-trans-anti
      BPDE-N(6)-dA residues at A(1) or A(2) within the TATA sequence element (5'
      ...TA(1)TAAA...-3')-(5'-...TTTA(2)TA...) were synthesized (anti-BPDE-N(6)-dA
      denotes an adduct formed from the reaction of r7,t8-dihydroxy-t9,10-epoxy
      7,8,9,10-tetrahydobenzo[a]pyrene). The formation of complexes with TBP of these
      two sequences in the double-stranded forms (1 nM) were studied employing
      electrophoretic mobility shift assays (EMSA) at different TBP concentrations (0
      70 nM). The overall affinity of TBP for the BPDE-modified target DNA sequences
      was weakly enhanced in the case of the (+)-trans or (-)-trans lesions positioned
      at site A(1) with K(d) approximately 8 and 6 nM, respectively (K(d) approximately
      9 nM for the unmodified TATA DNA). Higher-order TBP-DNA complexes were observed
      at TBP concentrations in excess of approximately 15 nM. However, the stabilities
      of the biologically significant monomeric TBP-DNA complexes was dramatically
      increased or decreased, depending on the position of the lesion (A(1) or A(2)),
      or on its stereochemical and conformational characteristics. A molecular docking
      modeling approach was employed to insert the stereoisomeric BPDE residues into
      the known TATA box-TBP structure [Nikolov, D. B., et al. (1996) Proc. Natl. Acad.
      Sci. U.S.A. 4862-4867] to rationalize these observations. Native gel
      electrophoresis experiments with the same duplexes without TBP indicate that none
      of the modified sequences exhibit unusual bending induced by the lesions, nor
      that they differ from one another in this respect. These results suggest that the
      hydrophobic, bulky BPDE residues influence the binding of TBP by mechanisms other
      than prebending. The efficiency of RNA transcription of TBP-controlled promoters
      could be strongly influenced by the presence of such bulky lesions that could
      adversely affect the levels of gene expression.

PMID- 11341828
TI  - Thermodynamics of peptide inhibitor binding to HIV-1 gp41.
AB  - The gp41 subunit of the human immunodeficiency virus type 1 envelope glycoprotein
      mediates fusion of the cellular and viral membranes. The gp41 ectodomain is a
      trimer of alpha-helical hairpins, where N-terminal helices form a parallel three
      stranded coiled-coil core and C-terminal helices pack around the core. A deep
      hydrophobic pocket on the N-terminal core represents an attractive target for
      antiviral therapeutics. We have employed a soluble derivative of the gp41 core
      ectodomain and small cyclic disulfide D-peptide inhibitors to define the
      stoichiometry, affinity, and thermodynamics of ligand binding to this pocket
      using isothermal titration calorimetry. These inhibitors bind with micromolar
      affinity to the pocket with the expected stoichiometry of three peptides per gp41
      core trimer. There are no cooperative interactions among the three binding sites.
      Linear eight- or nine-residue D-peptides derived from the pocket-binding domain
      of the cyclic molecules also bind specifically. A negative heat capacity change
      is observed and is consistent with burial of hydrophobic surface upon binding.
      Contrary to expectations for a reaction dominated by the classical hydrophobic
      effect, peptide binding is enthalpically driven and is opposed by an unfavorable
      negative entropy change. The calorimetry data support models whereby dominant
      negative inhibitors bind to a transiently exposed surface on the prefusion
      intermediate state of gp41 and disrupt subsequent resolution to the fusion-active
      six-stranded hairpin conformation.

PMID- 11341829
TI  - Small molecule peptidomimetics containing a novel phosphotyrosine bioisostere
      inhibit protein tyrosine phosphatase 1B and augment insulin action.
AB  - Protein tyrosine phosphatase 1B (PTP1B) attenuates insulin signaling by
      catalyzing dephosphorylation of insulin receptors (IR) and is an attractive
      target of potential new drugs for treating the insulin resistance that is central
      to type II diabetes. Several analogues of cholecystokinin(26)(-)(33) (CCK-8) were
      found to be surprisingly potent inhibitors of PTP1B, and a common N-terminal
      tripeptide, N-acetyl-Asp-Tyr(SO(3)H)-Nle-, was shown to be necessary and
      sufficient for inhibition. This tripeptide was modified to reduce size and
      peptide character, and to replace the metabolically unstable sulfotyrosyl group.
      This led to the discovery of a novel phosphotyrosine bioisostere, 2
      carboxymethoxybenzoic acid, and to analogues that were >100-fold more potent than
      the CCK-8 analogues and >10-fold selective for PTP1B over two other PTP enzymes
      (LAR and SHP-2), a dual specificity phosphatase (cdc25b), and a serine/threonine
      phosphatase (calcineurin). These inhibitors disrupted the binding of PTP1B to
      activated IR in vitro and prevented the loss of tyrosine kinase (IRTK) activity
      that accompanied PTP1B-catalyzed dephosphorylation of IR. Introduction of these
      poorly cell permeant inhibitors into insulin-treated cells by microinjection
      (oocytes) or by esterification to more lipophilic proinhibitors (3T3-L1
      adipocytes and L6 myocytes) resulted in increased potency, but not efficacy, of
      insulin. In some instances, PTP1B inhibitors were insulin-mimetic, suggesting
      that in unstimulated cells PTP1B may suppress basal IRTK activity. X-ray
      crystallography of PTP1B-inhibitor complexes revealed that binding of an
      inhibitor incorporating phenyl-O-malonic acid as a phosphotyrosine bioisostere
      occurred with the mobile WPD loop in the open conformation, while a closely
      related inhibitor with a 2-carboxymethoxybenzoic acid bioisostere bound with the
      WPD loop closed, perhaps accounting for its superior potency. These CCK-derived
      peptidomimetic inhibitors of PTP1B represent a novel template for further
      development of potent, selective inhibitors, and their cell activity further
      justifies the selection of PTP1B as a therapeutic target.

PMID- 11341830
TI  - Structural basis for the activity and substrate specificity of Erwinia
      chrysanthemi L-asparaginase.
AB  - Bacterial L-asparaginases, enzymes that catalyze the hydrolysis of L-asparagine
      to aspartic acid, have been used for over 30 years as therapeutic agents in the
      treatment of acute childhood lymphoblastic leukemia. Other substrates of
      asparaginases include L-glutamine, D-asparagine, and succinic acid monoamide. In
      this report, we present high-resolution crystal structures of the complexes of
      Erwinia chrysanthemi L-asparaginase (ErA) with the products of such reactions
      that also can serve as substrates, namely L-glutamic acid (L-Glu), D-aspartic
      acid (D-Asp), and succinic acid (Suc). Comparison of the four independent active
      sites within each complex indicates unique and specific binding of the ligand
      molecules; the mode of binding is also similar between complexes. The lack of the
      alpha-NH3(+) group in Suc, compared to L-Asp, does not affect the binding mode.
      The side chain of L-Glu, larger than that of L-Asp, causes several structural
      distortions in the ErA active side. The active site flexible loop (residues 15
      33) does not exhibit stable conformation, resulting in suboptimal orientation of
      the nucleophile, Thr15. Additionally, the delta-COO(-) plane of L-Glu is
      approximately perpendicular to the plane of gamma-COO(-) in L-Asp bound to the
      asparaginase active site. Binding of D-Asp to the ErA active site is very
      distinctive compared to the other ligands, suggesting that the low activity of
      ErA against D-Asp could be mainly attributed to the low k(cat) value. A
      comparison of the amino acid sequence and the crystal structure of ErA with those
      of other bacterial L-asparaginases shows that the presence of two active-site
      residues, Glu63(ErA) and Ser254(ErA), may correlate with significant glutaminase
      activity, while their substitution by Gln and Asn, respectively, may lead to
      minimal L-glutaminase activity.

PMID- 11341831
TI  - Crystal structure of the lytic transglycosylase from bacteriophage lambda in
      complex with hexa-N-acetylchitohexaose.
AB  - The three-dimensional structure of the lytic transglycosylase from bacteriophage
      lambda, also known as bacteriophage lambda lysozyme, complexed to the
      hexasaccharide inhibitor, hexa-N-acetylchitohexaose, has been determined by X-ray
      crystallography at 2.6 A resolution. The unit cell contains two molecules of the
      lytic transglycosylase with two hexasaccharides bound. Each enzyme molecule is
      found to interact with four N-acetylglucosamine units from one hexasaccharide
      (subsites A-D) and two N-acetylglucosamine units from the second hexasaccharide
      (subsites E and F), resulting in all six subsites of the active site of this
      enzyme being filled. This crystallographic structure, therefore, represents the
      first example of a lysozyme in which all subsites are occupied, and detailed
      protein-oligosaccharide interactions are now available for this bacteriophage
      lytic transglycosylase. Examination of the active site furthermore reveals that
      of the two residues that have been implicated in the reaction mechanism of most
      other c-type lysozymes (Glu35 and Asp52 in hen egg white lysozyme), only a
      homologous Glu residue is present. The lambda lytic transglycosylase is therefore
      functionally closely related to the Escherichia coli Slt70 and Slt35 lytic
      transglycosylases and goose egg white lysozyme which also lack the catalytic
      aspartic acid.

PMID- 11341832
TI  - Crystal structure of a novel red copper protein from Nitrosomonas europaea.
AB  - Nitrosocyanin (NC) is a mononuclear red copper protein isolated from the ammonia
      oxidizing bacterium Nitrosomonas europaea. Although NC exhibits some sequence
      homology to classic blue copper proteins, its spectroscopic and electrochemical
      properties are drastically different. The 1.65 A resolution crystal structure of
      oxidized NC reveals an unprecedented trimer of single domain cupredoxins. Each
      copper center is partially covered by an unusual extended beta-hairpin structure
      from an adjacent monomer. The copper ion is coordinated by His 98, His 103, Cys
      95, a single side chain oxygen of Glu 60, and a solvent molecule. In the 2.3 A
      resolution structure of reduced NC, His 98 shifts away from the copper ion, and
      the solvent molecule is not observed. The arrangement of these ligands renders
      the coordination geometry of the NC red copper center distinct from that of blue
      copper centers. In particular, the red copper center has a higher coordination
      number and lacks the long Cu-S(Met) and short Cu-S(Cys) bond distances
      characteristic of blue copper. Moreover, the red copper center is square
      pyramidal whereas blue copper is typically distorted tetrahedral. Analysis of the
      NC structure provides insight into possible functions of this new type of
      biological copper center.

PMID- 11341833
TI  - Short, strong hydrogen bonds at the active site of human acetylcholinesterase:
      proton NMR studies.
AB  - Cholinesterases use a Glu-His-Ser catalytic triad to enhance the nucleophilicity
      of the catalytic serine. We have previously shown by proton NMR that horse serum
      butyryl cholinesterase, like serine proteases, forms a short, strong hydrogen
      bond (SSHB) between the Glu-His pair upon binding mechanism-based inhibitors,
      which form tetrahedral adducts, analogous to the tetrahedral intermediates in
      catalysis [Viragh, C., et al. (2000) Biochemistry 39, 16200-16205]. We now extend
      these studies to human acetylcholinesterase, a 136 kDa homodimer. The free enzyme
      at pH 7.5 shows a proton resonance at 14.4 ppm assigned to an imidazole NH of the
      active-site histidine, but no deshielded proton resonances between 15 and 21 ppm.
      Addition of a 3-fold excess of the mechanism-based inhibitor m-(N,N,N
      trimethylammonio)trifluoroacetophenone (TMTFA) induced the complete loss of the
      14.4 ppm signal and the appearance of a broad, deshielded resonance of equal
      intensity with a chemical shift delta of 17.8 ppm and a D/H fractionation factor
      phi of 0.76 +/- 0.10, consistent with a SSHB between Glu and His of the catalytic
      triad. From an empirical correlation of delta with hydrogen bond lengths in small
      crystalline compounds, the length of this SSHB is 2.62 +/- 0.02 A, in agreement
      with the length of 2.63 +/- 0.03 A, independently obtained from phi. Upon
      addition of a 3-fold excess of the mechanism-based inhibitor 4-nitrophenyl
      diethyl phosphate (paraoxon) to the free enzyme at pH 7.5, and subsequent
      deethylation, two deshielded resonances of unequal intensity appeared at 16.6 and
      15.5 ppm, consistent with SSHBs with lengths of 2.63 +/- 0.02 and 2.65 +/- 0.02
      A, respectively, suggesting conformational heterogeneity of the active-site
      histidine as a hydrogen bond donor to either Glu-327 of the catalytic triad or to
      Glu-199, also in the active site. Conformational heterogeneity was confirmed with
      the methylphosphonate ester anion adduct of the active-site serine, which showed
      two deshielded resonances of equal intensity at 16.5 and 15.8 ppm with phi values
      of 0.47 +/- 0.10 and 0.49 +/- 0.10 corresponding to average hydrogen bond lengths
      of 2.59 +/- 0.04 and 2.61 +/- 0.04 A, respectively. Similarly, lowering the pH of
      the free enzyme to 5.1 to protonate the active-site histidine (pK(a) = 6.0 +/-
      0.4) resulted in the appearance of two deshielded resonances, at 17.7 and 16.4
      ppm, consistent with SSHBs with lengths of 2.62 +/- 0.02 and 2.63 +/- 0.02 A,
      respectively. The NMR-derived distances agree with those found in the X-ray
      structures of the homologous acetylcholinesterase from Torpedo californica
      complexed with TMTFA (2.66 +/- 0.28 A) and sarin (2.53 +/- 0.26 A) and at low pH
      (2.52 +/- 0.25 A). However, the order of magnitude greater precision of the NMR
      derived distances establishes the presence of SSHBs at the active site of
      acetylcholinesterase, and detect conformational heterogeneity of the active-site
      histidine. We suggest that the high catalytic power of cholinesterases results in
      part from the formation of a SSHB between Glu and His of the catalytic triad.

PMID- 11341834
TI  - Functional interrelationships in the alkaline phosphatase superfamily:
      phosphodiesterase activity of Escherichia coli alkaline phosphatase.
AB  - Escherichia coli alkaline phosphatase (AP) is a proficient phosphomonoesterase
      with two Zn(2+) ions in its active site. Sequence homology suggests a distant
      evolutionary relationship between AP and alkaline phosphodiesterase/nucleotide
      pyrophosphatase, with conservation of the catalytic metal ions. Furthermore, many
      other phosphodiesterases, although not evolutionarily related, have a similar
      active site configuration of divalent metal ions in their active sites. These
      observations led us to test whether AP could also catalyze the hydrolysis of
      phosphate diesters. The results described herein demonstrate that AP does have
      phosphodiesterase activity: the phosphatase and phosphodiesterase activities
      copurify over several steps; inorganic phosphate, a strong competitive inhibitor
      of AP, inhibits the phosphodiesterase and phosphatase activities with the same
      inhibition constant; a point mutation that weakens phosphate binding to AP
      correspondingly weakens phosphate inhibition of the phosphodiesterase activity;
      and mutation of active site residues substantially reduces both the mono- and
      diesterase activities. AP accelerates the rate of phosphate diester hydrolysis by
      10(11)-fold relative to the rate of the uncatalyzed reaction
      [(k(cat)/K(m))/k(w)]. Although this rate enhancement is substantial, it is at
      least 10(6)-fold less than the rate enhancement for AP-catalyzed phosphate
      monoester hydrolysis. Mutational analysis suggests that common active site
      features contribute to hydrolysis of both phosphate monoesters and phosphate
      diesters. However, mutation of the active site arginine to serine, R166S,
      decreases the monoesterase activity but not the diesterase activity, suggesting
      that the interaction of this arginine with the nonbridging oxygen(s) of the
      phosphate monoester substrate provides a substantial amount of the preferential
      hydrolysis of phosphate monoesters. The observation of phosphodiesterase activity
      extends the previous observation that AP has a low level of sulfatase activity,
      further establishing the functional interrelationships among the sulfatases,
      phosphatases, and phosphodiesterases within the evolutionarily related AP
      superfamily. The catalytic promiscuity of AP could have facilitated divergent
      evolution via gene duplication by providing a selective advantage upon which
      natural selection could have acted.

PMID- 11341835
TI  - Role of hydrogen bonding in the interaction between a xylan binding module and
      xylan.
AB  - NMR studies of the internal family 2b carbohydrate binding module (CBM2b-1) of
      Cellulomonas fimi xylanase 11A have identified six polar residues and two
      aromatic residues that interact with its target ligand, xylan. To investigate the
      importance of the various interactions, free energy and enthalpy changes have
      been measured for the binding of xylan to native and mutant forms of CBM2b-1. The
      data show that the two aromatic residues, Trp 259 and Trp 291, play a critical
      role in the binding, and similarly that mutants N264A and T316A have no affinity
      for the xylose polymer. Interestingly, mutations E257A, Q288A, N292A,
      E257A/Q288A, E257A/N292A, and E257A/N292A/Q288A do not significantly diminish the
      affinity of CBM2b-1 for the xylose polymers, but do influence the thermodynamics
      driving the protein-carbohydrate interactions. These thermodynamic parameters
      have been interpreted in light of a fresh understanding of enthalpy-entropy
      compensation and show the following. (1) For proteins whose ligands are bound on
      an exposed surface, hydrogen bonding confers little specificity or affinity. It
      also displays little cooperativity. Most specificity and affinity derive from
      binding between the face of sugar rings and aromatic rings. (2) Loss of hydrogen
      bonding interactions leads to a redistribution of the remaining bonding
      interactions such that the entropic mobility of the ligand is maximized, at the
      expense (if necessary) of enthalpically favorable bonds. (3) Changes in entropy
      and enthalpy in the binding between polysaccharide and a range of mutants can be
      interpreted by considering changes in binding and flexibility, without any need
      to consider solvent reorganization.

PMID- 11341836
TI  - An amino acid region at the N-terminus of rat hepatoma alpha1-->2
      fucosyltransferase modulates enzyme activity and interaction with lipids: strong
      preference for glycosphingolipids containing terminal Galbeta1-->3GalNAc
      structures.
AB  - A GDP-fucose:GM1 alpha1-->2 fucosyltransferase (FucT) is induced during early
      stages of chemical hepatocarcinogenesis in parenchymal cells of Fischer 344 rats
      fed a diet supplemented with 0.03% N-2-acetylaminofluorene (AAF). This enzyme is
      undetectable in normal rat liver tissues but is highly expressed in many rat
      hepatoma cell lines, including rat hepatoma H35 cells. Enzymatic properties and
      acceptor specificity of native rat hepatoma H35 cell alpha1-->2FucT, expressed
      recombinant full-length H35 cell alpha1-->2FucT, and a truncated form missing the
      first 27 amino acid residues from the N-terminus, comprising the cytoplasmic and
      transmembrane domains of the enzyme, were studied. The results indicate that the
      recombinant full-length enzyme has a specific activity over 80-fold higher than
      the truncated enzyme. Both the native and recombinant full-length enzymes display
      significant activity in the absence of detergent or phospholipid and optimal
      activity in the presence of Triton CF-54 detergent. The truncated enzyme is
      optimally activated by CHAPSO, showing little activity in its absence. These
      findings are in agreement with previous studies demonstrating a requirement of a
      lipidic environment for optimal activity with this enzyme and suggest that the N
      terminal transmembrane domain is important either in the maintenance of an active
      conformation or in allowing efficient interaction with acceptor glycolipids. Both
      the full-length and truncated enzymes transfer fucose not only to GM1 and asialo
      GM1 (Gg4) but also to galactosyl globoside (Gb5) as well. Weak or undetectable
      transfer to lacto- and neolacto-series acceptors was observed, demonstrating a
      strong preference for terminal Galbeta1-->3GalNAc- structures. The structures of
      two reaction products generated by expressed recombinant full-length alpha1-
      >2FucT, which are known to be important tumor-associated antigens (fucosyl-GM1
      and fucosyl-Gb5), were unambiguously confirmed by 1H-NMR spectral analysis.

PMID- 11341837
TI  - Structure of antibody-bound peptides and retro-inverso analogues. A transferred
      nuclear Overhauser effect spectroscopy and molecular dynamics approach.
AB  - The three-dimensional structures of the two L-peptides, H-CGGIRGERA-OH, called
      L(A), and H-CGGIRGERG-OH, called L(G), corresponding or close to the IRGERA
      sequence present in the C-terminal region (residues 130-135) of histone H3, and
      their retro-inverso analogues HO-mAreGriGGC-NH2, called RI(mA), and HO-mGreGriGGC
      NH2, called RI(mG), have been studied by two-dimensional 1H NMR and molecular
      dynamics calculations in association with a monoclonal antibody generated against
      L(A). At 25 degrees C, the affinity constants of the monoclonal antibody with
      respect to RI(mA) and RI(mG) were 75- and 270-fold higher than those measured
      with the homologous L(A) and L(G) peptides, respectively. Due to the spontaneous
      epimerization of the mA malonic residue, RI(mA) gave rise to two sets of
      resonances. With regard to the NH amide region, one set was similar to that for
      RI(mG) while the second was similar to those for the parent L-peptides L(A) and
      L(G). The antibody-bound conformations of the two couples of L- and retro-inverso
      peptides have been analyzed using molecular modeling calculations based on the
      transferred NOE interproton distances. Folded structures appeared in both cases
      with a type II' beta-turn in the parent GGIR sequence and a type I' beta-turn in
      the retro-inverso reGr sequence.

PMID- 11341838
TI  - Water penetration and binding to ferric myoglobin.
AB  - Flash photolysis investigations of horse heart metmyoglobin bound with NO
      (Mb(3+)NO) reveal the kinetics of water entry and binding to the heme iron.
      Photodissociation of NO leaves the sample in the dehydrated Mb(3+) (5-coordinate)
      state. After NO photolysis and escape, a water molecule enters the heme pocket
      and binds to the heme iron, forming the 6-coordinate aquometMb state (Mb(3+)H2O).
      At longer times, NO displaces the H2O ligand to reestablish equilibrium. At 293
      K, we determine a value k(w) approximately 5.7 x 10(6) s(-1) for the rate of H2O
      binding and estimate the H2O dissociation constant as 60 mM. The Arrhenius
      barrier height H(w) = 42 +/- 3 kJ/mol determined for H2O binding is identical to
      the barrier for CO escape after photolysis of Mb(2+)CO, within experimental
      uncertainty, consistent with a common mechanism for entry and exit of small
      molecules from the heme pocket. We propose that both processes are gated by
      displacement of His-64 from the heme pocket. We also observe that the bimolecular
      NO rebinding rate is enhanced by 3 orders of magnitude both for the H64L mutant,
      which does not bind water, and for the H64G mutant, where the bound water is no
      longer stabilized by hydrogen bonding with His-64. These results emphasize the
      importance of the hydrogen bond in stabilizing H2O binding and thus preventing NO
      scavenging by ferric heme proteins at physiological NO concentrations.

PMID- 11341839
TI  - Recognition and kinetics for excision of a base lesion within clustered DNA
      damage by the Escherichia coli proteins Fpg and Nth.
AB  - Ionizing radiation and radiomimetic anticancer agents induce clustered DNA
      damages that are thought to lead to deleterious biological consequences, due to
      the challenge that clustered damage may present to the repair machinery of the
      cell. Specific oligonucleotides, containing either dihydrothymine (DHT) or 7,8
      dihydro-8-oxoguanine (8-oxoG) opposite to specific lesions at defined positions
      on the complementary strand, have been used to determine the kinetic constants,
      K(M), k(cat), and specificity constants, for excision of DHT and 8-oxoG by the
      Escherichia coli base excision repair proteins, endonuclease III (Nth) and
      formamidopyrimidine glycosylase (Fpg), respectively. For excision of DHT opposite
      to 8-oxoadenine by Nth or Fpg proteins, or 8-oxoG opposite to 8-oxoG by Fpg, the
      major change in the specificity constant occurs when the second lesion on the
      complementary strand is one base to the site opposite to DHT or 8-oxoG. The
      specificity constants for excision of DHT or 8-oxoG by both proteins are reduced
      by up to 2 orders of magnitude when an abasic site or a strand break is opposite
      on the complementary strand. Whereas the values of K(M) are only slightly
      affected by the presence of a second lesion, the major change is seen as a
      reduction in the values of k(cat). The binding of Fpg protein to oligonucleotides
      containing 8-oxoG is inhibited, particularly when a single strand break is near
      to 8-oxoG on the complementary strand. It is inferred that not only the binding
      affinity of Fpg protein to the base lesion but also the rate of excision of the
      damaged base is reduced by the presence of another lesion, particularly a single
      strand break or an AP site on the complementary strand.

PMID- 11341841
TI  - Caldesmon reduces the apparent rate of binding of myosin S1 to actin-tropomyosin.
AB  - Equilibrium measurements of the rate of binding of caldesmon and myosin S1 to
      actin-tropomyosin from different laboratories have yielded different results and
      have led to different models of caldesmon function. An alternate approach to
      answering these questions is to study the kinetics of binding of both caldesmon
      and S1 to actin. We observed that caldesmon decreased the rate of binding of S1
      to actin in a concentration-dependent manner. The inhibition of the rate of S1
      binding was enhanced by tropomyosin, but the effect of tropomyosin on the binding
      was small. Premixing actin with S1 reduced the amplitude (extent) of caldesmon
      binding in proportion to the fraction of actin that contained bound S1, but the
      rate of binding of caldesmon to free sites was not greatly altered. No evidence
      for a stable caldesmon-actin-tropomyosin-S1 complex was observed, although S1 did
      apparently bind to gaps between caldesmon molecules. These results indicate that
      experiments involving caldesmon, actin, tropomyosin, and myosin are inherently
      complex. When the concentration of either S1 or caldesmon is varied, the amount
      of the other component bound to actin-tropomyosin cannot be assumed to remain
      fixed. The results are not readily explained by a mechanism in which caldesmon
      acts only by stabilizing an inactive state of actin-tropomyosin. The results
      support regulatory mechanisms that involve changes in the actin-S1 interaction.

PMID- 11341840
TI  - Methylation of histone H3 by coactivator-associated arginine methyltransferase 1.
AB  - The preferential in vitro methylation of histone H3 by coactivator-associated
      arginine methyltransferase 1 (CARM1) has been proposed as a basis for its ability
      to enhance gene transcription [Chen, D., et al. (1999) Science 284, 2174-2177].
      To further evaluate the significance of H3 methylation, we studied the kinetics
      and site specificity of its modification by CARM1. Affinity-purified CARM1
      methylated recombinant chick H3, which is free of posttranslational
      modifications, and calf thymus H3, which is heterogeneous with regard to
      preexisting modifications, equally well, exhibiting a V(max) of 4500 pmol min(-1)
      (mg of enzyme)(-1) and an apparent K(m) for H3 of < or = 0.2 microM. The
      catalytic efficiency (k(cat)/K(m)) of CARM1 toward H3 was at least 1000 times
      that toward R1 (GGFGGRGGFGG-amide), a highly effective substrate for protein
      arginine methyltransferase 1. Peptide mapping of 3H-methyl-labeled H3 indicated
      methylation at Arg-2, Arg-17, and Arg-26 in the N-terminal region and at one or
      more of four arginines (128/129/131/134) at the C-terminus. Two of the N-terminal
      sites, Arg-17 and Arg-26, occur in the sequence KAXRK and appear to be more
      efficiently methylated than Arg-2. CARM1 catalyzed formation of N(G),N(G)
      dimethylarginine (asymmetric) but little or no N(G),N'(G)-dimethylarginine
      (symmetric) and no form of methyllysine. Amino acid analysis of untreated calf
      thymus H3 revealed that 3.7% of the molecules naturally contain asymmetric
      dimethylarginine and/or monomethylarginine. Our findings support the hypothesis
      that methylation of H3 may be involved in the mechanism of transcriptional
      coactivation by CARM1 of genes whose expression is under the control of nuclear
      receptors.

PMID- 11341843
TI  - Design of Gram-negative selective antimicrobial peptides.
AB  - Lipopolysaccharide (LPS), a major component of Gram-negative bacteria, signals
      bacterial invasion and triggers defensive host responses. However, excessive
      responses also lead to the serious pathophysiological consequence of septic
      shock. To develop Gram-negative selective compounds that can inhibit the effects
      of LPS-induced sepsis, we have designed constrained cyclic antimicrobial peptides
      based on a cystine-stabilized beta-stranded framework mimicking the putative LPS
      binding sites of the LPS-binding protein family. Our prototype termed R4A,
      c(PACRCRAG-PARCRCAG), consists of an eight amino acid degenerated repeat
      constrained by a head-to-tail cyclic peptide backbone and two cross-bracing
      disulfides. NMR study of K4A, an R4A analogue with four Arg --> Lys replacements,
      confirmed the amphipathic design elements with four Lys on one face of the
      antiparallel beta-strand and two hydrophobic cystine pairs plus two Ala on the
      opposite face. K4A and R4A displayed moderate microbicidal potency and Gram
      negative selectivity. However, R4A analogues with single or multiple replacements
      of Ala and Gly with Arg or bulky hydrophobic amino acids displayed increased
      potency and selectivity in both low- and high-salt conditions. Analogues R5L and
      R6Y containing additional cationic and bulky hydrophobic amino acids proved the
      best mimics of the amphipathic topology of the "active-site" beta-strands of LPS
      binding proteins. They displayed potent activity against Gram-negative E. coli
      with a minimal inhibitory concentration of 20 nM and a >200-fold selectivity over
      Gram-positive S. aureus. Our results suggest that an LPS-targeted design may
      present an effective approach for preparing selective peptide antibiotics.

PMID- 11341842
TI  - Catalytic function of nongastric H,K-ATPase expressed in Sf-21 insect cells.
AB  - We previously demonstrated that the alpha-subunit of human nongastric H,K-ATPase
      (Atp1al1) can assemble with the gastric H,K-ATPase beta-subunit (betaHK) into an
      active ion pump upon coexpression in Xenopus oocytes. To gain insight into
      enzymatic functions, we have analyzed the Atp1al1-betaHK complex using a
      baculovirus expression system. The efficient formation of the functional Atp1al1
      betaHK complex in membranes of Sf-21 insect cells was obtained upon co-infection
      with recombinant baculoviruses expressing Atp1al1 and betaHK. Expression of
      either protein alone did not produce active ATPase. The effects of K(+), Na(+),
      pH, and ATP and inhibitors on ATPase activity of the recombinant Atp1al1-betaHK
      complex were analyzed. The Atp1al1-betaHK complex was shown to exhibit
      significant ATPase activity in nominally K(+)-free medium. The addition of K(+)
      stimulated the ATP hydrolysis up to 3-fold with K(m) approximately 116 microM
      K(+). The ATPase activity was moderately sensitive to ouabain and to SCH 28080
      with apparent K(i) values in K(+)-free medium of approximately 64 microM and
      approximately 93 microM, respectively. Potassium exhibited strong antagonism
      toward both inhibitors. Assays of the ouabain-sensitive ATPase activity revealed
      inhibitory effects of Na(+) with the apparent K(i) of approximately 24 mM in the
      absence of added K(+) and with K(i) within the range of 60-70 mM in the presence
      of > or = 1 mM K(+). Thus, the human nongastric H,K-ATPase represented by the
      recombinant Atp1al1-betaHK complex exhibits enzymatic properties of K(+)
      dependent ATPase sensitive to ouabain, SCH 28080, and Na(+). It differs from Na,K
      ATPase in cation dependence and differs from gastric H,K-ATPase and Na,K-ATPase
      in sensitivity to inhibitors.

PMID- 11341844
TI  - Developmental and cell-cycle regulation of Caenorhabditis elegans HCF
      phosphorylation.
AB  - HCF-1 is a mammalian protein required for cell proliferation. It is also involved
      in transcriptional activation of herpes-simplex-virus immediate-early gene
      transcription in association with the viral transactivator VP16. HCF-1 and a
      related protein called HCF-2 possess a homologue in Caenorhabditis elegans that
      can associate with and activate VP16. Here, we demonstrate developmental
      regulation of C. elegans HCF (CeHCF) phosphorylation: a hyperphosphorylated form
      of CeHCF is present in embryos, whereas a hypophosphorylated form is present in
      L1 larvae. The phosphorylation patterns of endogenous CeHCF in worms and
      ectopically synthesized CeHCF in mammalian cells are remarkably similar,
      suggesting that the way CeHCF can be recognized by kinases is conserved in
      animals. Phosphorylation-site mapping of endogenous CeHCF, however, revealed that
      phosphorylation occurs at four clustered sites in the region of the protein that
      is not highly conserved among HCF proteins and is not required for VP16-induced
      complex formation. Indeed, phosphorylation of either CeHCF or human HCF-1 appears
      to be dispensable for association with VP16. All four CeHCF phosphorylation sites
      match the consensus recognition site for the cell-cycle kinases CDC2 and CDK2.
      Consistent with this similarity and with the developmental phosphorylation of
      CeHCF in C. elegans embryos, CeHCF phosphorylation is cell-cycle-regulated in
      mammalian cells.

PMID- 11341845
TI  - Kinetic analysis of matrix metalloproteinase activity using fluorogenic triple
      helical substrates.
AB  - Matrix metalloproteinase (MMP) family members are involved in the physiological
      remodeling of tissues and embryonic development as well as pathological
      destruction of extracellular matrix components. To study the mechanisms of MMP
      action on collagenous substrates, we have constructed homotrimeric, fluorogenic
      triple-helical peptide (THP) models of the MMP-1 cleavage site in type II
      collagen. The substrates were designed to incorporate the fluorophore/quencher
      pair of (7-methoxycoumarin-4-yl)acetyl (Mca) and N-2,4-dinitrophenyl (Dnp) in the
      P(5) and P(5)' positions, respectively. In addition, Arg was incorporated in the
      P(2)' and P(8)' positions to enhance enzyme activity and improve substrate
      solubility. The desired sequences were Gly-Pro-Lys(Mca)-Gly-Pro-Gln-Gly
      approximately Leu-Arg-Gly-Gln-Lys(Dnp)-Gly-Ile/Val-Arg. Two fluorogenic
      substrates were prepared, one using a covalent branching protocol (fTHP-1) and
      one using a peptide self-assembly approach (fTHP-3). An analogous single-stranded
      substrate (fSSP-3) was also synthesized. Both THPs were hydrolyzed by MMP-1 at
      the Gly approximately Leu bond, analogous to the bond cleaved in the native
      collagen. The individual kinetic parameters for MMP-1 hydrolysis of fTHP-3 were
      k(cat) = 0.080 s(-1) and K(M) = 61.2 microM. Subsequent investigations showed
      fTHP-3 hydrolysis by MMP-2, MMP-3, MMP-13, a C-terminal domain-deleted MMP-1 [MMP
      1(Delta(243-450))], and a C-terminal domain-deleted MMP-3 [MMP-3(Delta(248
      460))]. The order of k(cat)/K(M) values was MMP-13 > MMP-1 approximately MMP
      1(Delta(243-450)) approximately MMP-2 >> MMP-3 approximately MMP-3(Delta(248
      460)). Studies on the effect of temperature on fTHP-3 and fSSP-3 hydrolysis by
      MMP-1 showed that the activation energies between these two substrates differed
      by 3.4-fold, similar to the difference in activation energies for MMP-1
      hydrolysis of type I collagen and gelatin. This indicates that fluorogenic triple
      helical substrates mimic the behavior of the native collagen substrate and may be
      useful for the investigation of collagenase triple-helical activity.

PMID- 11341846
TI  - Slow-binding inhibition of gamma-glutamyl transpeptidase by gamma-boroGlu.
AB  - gamma-Glutamyl transpeptidase (gammaGTase) catalyzes the transfer of the gamma
      glutamyl moiety of gamma-glutamyl-derived peptides, such as glutathione (gammaGlu
      Cys-Gly), and anilides, such as gamma-glutamyl-7-amido-4-methylcoumarin (gammaGlu
      AMC), to acceptor molecules, including water and various dipeptides. These acyl
      transfer reactions all occur through a common acyl-enzyme intermediate formed
      from attack of an active site hydroxyl on the gamma-carbonyl carbon of gammaGlu-X
      with displacement of X. In this paper, we report that gammaGTase is potently
      inhibited by the gamma-boronic acid analogue of L-glutamic acid, 3-amino-3
      carboxypropaneboronic acid (gamma-boroGlu). We propose that gamma-boroGlu adds to
      the active site hydroxyl of gammaGTase to form a covalent, tetrahedral adduct
      that resembles tetrahedral transition states and intermediates that occur along
      the reaction pathway for gammaGTase-catalyzed reactions. Our studies demonstrate
      that gamma-boroGlu is a competitive inhibitor of the gammaGTase-catalyzed
      hydrolysis of gammaGlu-AMC with a K(i) value of 35 nM. Kinetics of inhibition
      studies allow us to estimate the following values: k(on) = 400 mM(-1) s(-1) and
      k(off) = 0.02 s(-1). We also found that gamma-boroGlu is an uncompetitive
      inhibitor of Gly-Gly-promoted transamidation of gammaGlu-AMC. This observation is
      consistent with the kinetic mechanism we determined for gammaGTase-catalyzed
      transamidation of gammaGlu-AMC by Gly-Gly to form gammaGlu-Gly-Gly. To probe rate
      limiting transition states for gammaGTase catalysis and inhibition, we determined
      solvent deuterium isotope effects. Solvent isotope effects on k(c)/K(m) for
      hydrolysis of gammaGlu-AMC and k(on) for inhibition by gamma-boroGlu are
      identical and equal unity, suggesting that the processes governed by these rate
      constants are both rate-limited by a step that is insensitive to solvent
      deuterium such as a conformational fluctuation of the initially formed E-S or E-I
      complex. In contrast, the solvent isotope effect on k(c) is 2.4. k(c) is rate
      limited by hydrolysis of the acyl-enzyme intermediate that is formed during
      reaction of gammaGTase with gammaGlu-AMC. Thus, the magnitude of this isotope
      effect suggests the formation of a catalytically important protonic bridge in the
      rate-limiting transition state for deacylation.

PMID- 11341847
TI  - Temperature and driving force dependence of the folding rate of reduced horse
      heart cytochrome c.
AB  - Utilizing the stability difference between the ferro and ferri forms of horse
      heart cytochrome c (cyt c), folding of reduced cyt c was triggered by laser
      induced reduction of unfolded oxidized cyt c. Measurements were made of the
      kinetics of the main folding phase (1 ms-10 s) in which collapsed reduced cyt c
      transforms to the native conformation. The folding rates were studied extensively
      as a function of temperature (5-75 degrees C) and guanidine hydrochloride
      (GdnHCl) concentration (1.6-4.9 M). At constant [GdnHCl], the Arrhenius plot of
      the folding rate constant (k) is nonlinear. At temperatures above 40 degrees C,
      the decrease in protein stability counteracts the expected increase in folding
      rate. Introducing free energy (DeltaG), derived from protein stability data, into
      the Eyring and Arrhenius equations leads to: ln k = ln(k(b)T/h) + DeltaS()/R -
      DeltaH()/RT - theta(m)DeltaG/RT = ln A - E(a)/RT - theta(m)DeltaG/RT, where
      theta(m) is the ratio between the denaturant dependence of the folding rate and
      the stability. By using this equation at constant DeltaG [or constant equilibrium
      constant (K)], linear Arrhenius plots are obtained. For the main folding phase of
      reduced cyt c, a positive DeltaS() is obtained indicating that the transition
      state is less ordered than the reactant. A model is proposed in which reduced cyt
      c first collapses into a compact intermediate, which needs to expand to reach the
      transition state of the rate-limiting folding reaction.

PMID- 11341848
TI  - Secondary stabilization reactions and proton-coupled electron transport in
      photosystem II investigated by electroluminescence and fluorescence spectroscopy.
AB  - The oxidized primary electron donor in photosystem II, P(680)(+), is reduced in
      several phases, extending over 4 orders of magnitude in time. Especially the
      slower phases may reflect the back-pressure exerted by water oxidation and
      provide information on the reactions involved. The kinetics of secondary electron
      transfer reactions in the microseconds time range after charge separation were
      investigated in oxygen-evolving thylakoids suspended in H2O or D2O. Flash-induced
      changes of chlorophyll fluorescence yield and electric field-induced
      recombination luminescence were decomposed into contributions from oxidation
      states S(0), S(1), S(2), and S(3) of the oxygen-evolving complex and interpreted
      in terms of stabilization kinetics of the initial charge-separated state
      S(j)Y(Z)P(680)(+)Q(A)(-)Q(B). In approximately 10% of the centers, only charge
      recombination took place. Otherwise, no static heterogeneity was involved in the
      microsecond reduction of P(680)(+) by Y(Z) (stabilization) or Q(A)(-)
      (recombination). The recombination component in active centers occurs mainly upon
      charge separation in S(3), and, in the presence of D2O, in S(2) as well and is
      tentatively attributed to the presence of Y(Z)(ox)S(j-1) in equilibrium with
      Y(Z)S(j). A 20-30 micros stabilization occurs in all S-states, but to different
      extents. Possible mechanisms for this component are discussed. D2O was found to
      decrease: (i) the rate of the reaction Y(Z)(ox)S(1) to Y(Z)S(2), (ii) the
      equilibrium constant between P680(+)Y(Z)S(2) and P(680)Y(Z)(ox)S(2), (iii) the
      rate of the slow phase of P(680)(+) reduction for the S(3) --> S(0) transition,
      and (iv) the rate of electron transfer from Q(A)(-) to Q(B) /Q(B)(-). The
      increased 'miss probability' in D2O is due to (iii).

PMID- 11341849
TI  - Biological implication of conformational flexibility in ouabain: observations
      with two ouabain phosphate isomers.
AB  - Ouabain is a highly polar and unusually potent sodium pump inhibitor that
      possesses uncommon conformational flexibility in its steroid A-ring moiety. The
      biological significance of ring flection in the cardiotonic steroids has not been
      described. Accordingly, we prepared ouabain 1,5,19- and 1,11,19-phosphates. The
      former stabilizes the steroid A-ring chair conformation and the latter locks the
      A-ring in the half-boat conformation and decreases flection of the ABC-ring
      moiety. Using a dog kidney cell line (MDCK) in a pH microphysiometer
      (Cytosensor), ouabain and its 1,5,19-phosphate at 10(-5) M reduced the rate of
      extracellular acidification by 15-20%. During inhibitor washout, the rate of
      recovery from the 1,5,19-phosphate analogue was approximately 3 times faster than
      ouabain. The 1,11,19-phosphate at 10(-4) M elicited a weak ( approximately 7%)
      response, and the effects reversed approximately 44-fold faster than ouabain.
      Studies with purified Na(+),K(+)-ATPase showed that ouabain and its 1,5,19
      phosphate analogue were of similar efficacy (EC(50) = 1.1 and 5.2 x 10(-7) M,
      respectively) and >100-fold more potent than the 1,11,19-phosphate analogue.
      Studies of the binding kinetics showed that the 1,5,19-phosphate analogue bound 3
      fold and dissociated 16-fold faster from the purified Na(+),K(+)-ATPase than
      ouabain. Both analogues were competitive inhibitors of 3H-ouabain binding. Taken
      together, these results suggest that the marked conformational flexibility of the
      A-ring in ouabain ordinarily slows the initial binding of this steroid to the
      sodium pump. However, once ouabain is bound, flection of the steroidal A- and BC
      rings is critical for the maintenance of high-affinity binding. Our results
      indicate that the ouabain-binding site is comprised of structurally mobile
      elements and highlight the roles that synchronization between receptor and ligand
      dynamics play as determinants of biological activity in this system.

PMID- 11341850
TI  - New directions in the genetic mechanisms underlying nicotine addiction.
AB  - Major advances have been made in understanding nicotine addiction and smoking
      behaviour in recent years. In particular, evidence for the relative importance of
      genetic and environmental effects on smoking initiation and persistence has
      emerged from behaviour genetic studies. These data have supported evidence from
      molecular genetic studies for the role of particular candidate genes in tobacco
      dependence. Studies of the personality correlates of smoking behaviour suggest
      that these factors mediate the association between genetics and smoking
      initiation, while learning models of nicotine addiction suggest a role for
      dopaminergic genes in facilitating neuroadaptations associated with smoking
      persistence and development of nicotine dependence. Integrating these different
      avenues of research represents one of the most interesting and potentially
      fruitful ventures in the treatment of tobacco dependence.

PMID- 11341851
TI  - Alcohol tolerance and nicotine cross-tolerance in adolescent mice.
AB  - The present experiment was designed to evaluate the development of tolerance to
      alcohol and cross-tolerance to nicotine in adolescent mice. C57BL/6J mice (30-40
      days old) were injected IP with alcohol (2.5 g/kg) for 4 consecutive days. A
      control group received four saline injections. On the test day, all subjects
      received an alcohol injection. Tolerance to alcohol's hypothermic effect was
      observed. Mice (male and female) exposed to alcohol for the 4 previous days
      showed less hypothermic response to an alcohol challenge than animals injected
      for 4 days with saline and then challenged with alcohol. Tolerance to alcohol's
      motor incoordinating effects and differences in blood alcohol concentrations were
      not observed. Thirty days following alcohol treatment, the same mice received a
      single nicotine injection (1 mg/kg) to assess cross-tolerance. Nicotine's effect
      on locomotor activity (open field test) and rectal temperature varied as a
      function of prior adolescent alcohol exposure and gender. Specifically, female
      mice who had been exposed to alcohol administrations were more resistant to
      nicotine's effect on locomotion and temperature than saline-treated animals. In
      summary, these data demonstrate that adolescent mice develop tolerance to some,
      but not all, alcohol-induced responses, and that female mice are cross-tolerant
      to nicotine's effects on temperature and activity.

PMID- 11341852
TI  - Effects of central and systemic injections of peripheral benzodiazepine receptor
      ligands on the anxiolytic actions of ethanol in rats.
AB  - The influence of peripheral benzodiazepine receptor ligands Ro5-4864 (0.05 or 1.0
      mg/kg, i.p.) or PK11195 (0.05 or 1.0 mg/kg, i.p.) on the anxiolytic effect of
      ethanol (1.2 g/kg; 14% p/v; i.p.) was investigated in rats tested on the elevated
      plus-maze. Other animals were injected through intrahippocampal administrations
      of the ligands (0.5 or 1.0 nmol/0.5 &mgr;l) before ethanol (1.2g/kg; 14% p/v;
      i.p.) and submitted to the elevated plus-maze test. The results showed that the
      systemic administration of either ligands 24 hours before the ethanol treatment
      resulted in a reduced anxiolytic effect of this drug. Only PK11195 reversed the
      effect of ethanol after intrahippocampal injection. These data suggest that
      peripheral benzodiazepine receptors play a role in ethanol anxiolysis.

PMID- 11341853
TI  - The effect of tobacco smoking on subjective symptoms of inadequacy ("not
      holding") of methadone dose among opiate addicts in methadone maintenance
      treatment.
AB  - The objective of this study was to examine the relationship between subjective
      symptoms of inadequacy of methadone dose (not feeling "held") and tobacco smoking
      in patients in methadone maintenance treatment (MMT). This was a cross-sectional
      study of smoking behaviour, investigating subjective, physiological and
      psychological symptoms. The study took place in a community-based methadone
      maintenance clinic of a psychiatric teaching hospital in South London. Fifty
      adult opiate addicts (37 males and 13 females) were on a stable daily methadone
      dose; the number of cigarettes smoked during the day and previous day of
      investigation, salivary cotinine measurements and carbon monoxide (CO) from
      expired air were measured. The Methadone Symptom Checklist (MSC) was used to
      score withdrawal symptoms encountered in patients not feeling "held" during MMT
      The Hamilton Anxiety Score was also used. The prevalence of tobacco-smoking was
      high (98%), with two-thirds (68%) smoking self-fabricated cigarettes ("roll
      ups"). Scores from rating scales measuring symptoms of not being "held"
      correlated with number of cigarettes smoked the previous day (p < 0.05). A
      similar correlation was found with the Hamilton Anxiety Score. However, there was
      no correlation between rating scale scores and either salivary cotinine
      concentration or CO from expired air. Methadone patients who smoke more are
      significantly more likely to report problems of not feeling "held" by their
      methadone dose and they also show a higher level of anxiety. However, this
      increased cigarette consumption is not reflected in increased salivary continine
      levels or levels of CO in expired air, and it may be that the raised level of
      anxiety leads to a smoking-pattern consisting of frequent lighting-up of
      cigarettes or "roll-ups" which are consumed incompletely and/or not smoked by
      inhalation.

PMID- 11341854
TI  - The impact of naloxone/lofexidine combination treatment on the opiate withdrawal
      syndrome.
AB  - Clinical studies in opiate-dependent patients suggest that detoxification
      treatment with opiate antagonists may accelerate the resolution of the opiate
      withdrawal syndrome, permitting early induction onto naltrexone maintenance
      treatment. The present open study compared the clinical efficacy of daily
      naloxone injections in conjunction with lofexidine, with conventional lofexidine
      monotherapy, in 49 polysubstance-misusing opiate-dependent patients. Overall, the
      addition of naloxone did not confer substantial benefit over lofexidine
      monotherapy, although area-under-the-curve analysis showed that withdrawal
      severity in the naloxone/lofexidine combination group was significantly less than
      in the lofexidine monotherapy group, who experienced more severe withdrawal
      symptoms on days 4, 7, 9 and 13 of treatment. There were no significant
      differences in rates of completion of detoxification. Blood pressure remained
      within normal limits in both groups. Naltrexone maintenance treatment
      acceptability was low; only four patients continued with treatment for 5 or more
      days. The modest benefit of adding naloxone to lofexidine compared to the
      findings of previous opiate antagonist detoxification treatment studies is
      discussed in the context of the hypothesis that a critical level of opiate
      receptor occupancy is required to accelerate resolution of opiate withdrawal; the
      neurochemical mechanisms which may promote this are discussed.

PMID- 11341855
TI  - Salivary cortisol during opiate dependence and withdrawal.
AB  - Seventeen inpatients (14 men, three women) with opiate dependence and
      polysubstance misuse participated in a longitudinal study of salivary cortisol
      secretion during and after lofexidine detoxification treatment. Both opiate
      withdrawal symptoms and salivary cortisol were measured every morning for up to
      25 days. Results were compared with a control group of 10 normal volunteers.
      There was an 80% reduction in withdrawal symptom severity between the first 12
      days and the subsequent 12 days of treatment. Salivary cortisol fell from a mean
      of 22.3 nm/l over days 1-12 to 18.5 nm/l during days 13-25, a reduction of 17%.
      Salivary cortisol concentration correlated significantly with withdrawal symptom
      severity. Salivary cortisol levels remained significantly higher than controls
      for the duration of the study. The study supports a role for hypothalamo
      pituitary-adrenal (HPA) activation in opiate withdrawal. The contribution of
      persistant dysregulation of the HPA, found in this study, to the vulnerability
      for relapse after abstinence has been achieved, is discussed.

PMID- 11341856
TI  - Impaired sleep during the post-alcohol withdrawal period in alcoholic patients.
AB  - Twenty-seven patients who suffered from alcohol dependence syndrome and who were
      admitted to the Department of Psychiatry at NCNP were investigated for impaired
      sleep. The incidence of "insomnia night", when a patient has trouble getting
      sufficient sleep even after taking additional drugs for insomnia, was used as the
      index for impaired sleep. "Insomnia night" was observed among 51.9% (14 of 27) of
      the patients during administration; 18.5% (nine of 27) experienced "insomnia
      night" only during the withdrawal period. The mean incidence was 3.5 nights of 10
      nights for 0-9th day after abstinence and 2.0 nights of 10 nights for 10-19th day
      after abstinence; 33.3% (nine of 27) claimed "insomnia night" even after the
      withdrawal period and the highest incidence was the 160-169th day after
      abstinence, average frequency being 4.4 nights of 10 nights. Impaired sleep
      emerging after the withdrawal period neared the clinical course of Komiyama's
      protracted withdrawal symptoms, thus suggesting that it might be one of the
      protracted withdrawal symptoms.

PMID- 11341857
TI  - Influence of concomitant drugs on methadone elimination half-life in patients
      under a maintenance treatment.
AB  - Methadone elimination half-life was determined in 18 patients under maintenance
      treatments and found to range from 2.05 to 49.6 h. A study of potential
      correlations between this parameter and the presence of concomitant drugs,
      inhibitors or inducers of cytochrome P450, revealed an increase or decrease of
      methadone elimination half-life, respectively. Twenty-four-hour urinary excretion
      of methadone was determined in three patients, who were found to release 22.3
      49.8% of the dose taken. The amount excreted varied with the chemical form
      (unaltered drug or its main metabolite) in the three cases. No statistically
      significant correlation was found between urine pH and the elimination half-life
      (p < 0.50).

PMID- 11341858
TI  - Phenylalkylamine abuse among opiate addicts attending a methadone treatment
      programme in the Republic of Ireland.
AB  - Since the early 1990s ring-substituted derivatives of amphetamine have been
      abused widely in the Republic of Ireland. The main ring-substituted amphetamines
      being abused include methylenedioxyamphetamine (MDA),
      methylenedioxymethamphetamine (MDMA) and methylenedioxyethamphetamine (MDEA). A
      newer illicit synthetic analogue, which has been seized to a lesser extent by
      Irish police, is N-methyl-1-(3,4-methylenedioxyphenyl)-2-butanamine (MBDB). The
      work presented here involved the determination of the type of ring-substituted
      amphetamines being abused by a group of recovering opiate abusers participating
      in a methadone maintenance programme in a Dublin Drug Rehabilitation Centre.
      Urine samples which tested positive for amphetamines and ring-substituted
      amphetamines via EMIT immunoassay were subjected to further analysis using GC-MS
      with MBTFA flash derivatization. It was found that the methylenedioxypropanamines
      were being abused, as was amphetamine itself. However, no abuse of
      methylenedioxybutanamines or thioamphetamines was observed.

PMID- 11341859
TI  - The cannabinoid receptor gene (CNR1) is not affected in German i.v. drug users.
AB  - The aim of the study was to investigate a possible contribution of the
      cannabinoid receptor gene (CNR1) to the development of i.v. drug addiction.
      Allele and genotype frequencies of a previously associated flanking triplet
      repeat polymorphism were compared between patients and controls, and the whole
      coding region of the CNR1 gene of all patients were screened for presence of
      mutations. The study took place at the Addiction Treatment Unit of the Medical
      School Hannover, and two outpatients' departments in Hannover, Germany. Forty
      German unrelated opioid addicts (27 males and 13 females; mean age 37.9 years;
      range 16-53 years), took part, all of them satisfying ICD-10 and DSM-IV
      diagnostic criteria for opioid dependence and 81 age- and sex-matched controls
      (German blood donors). Measurements used were lengths of alleles, genotyping and
      single strand conformation polymorphism (SSCP) analysis. Neither the >/= 5
      alleles of the extragenic triplet repeat (AAT) marker nor the alleles of an
      intragenic biallelic CNR1 polymorphism (1359G/A) were associated with i.v. drug
      use in our study group. In addition, we did not detect any sequence variation
      within the CNR1 gene which could confer susceptibility to i.v. drug abuse. In
      contrast to previous investigations, we found no evidence for an involvement of
      the CNR1 gene in i.v. drug addiction.

PMID- 11341862
TI  - Intermittent Claudication.
AB  - Intermittent claudication is the most common symptom in patients with peripheral
      arterial disease (PAD). As such, it is mandatory for clinicians to treat both the
      PAD-specific symptoms (to decrease functional impairment and thereby improve
      quality- of-life, as well as to decrease rates of amputation) and the underlying
      systemic atherosclerosis (and thereby reduce cardiovascular ischemic events,
      especially myocardial infarction and stroke). Most patients with claudication can
      successfully decrease their exertional limb symptoms via a combination of
      exercise (preferably supervised) and pharmacotherapeutic interventions (eg,
      cilostazol). Endovascular revascularization currently serves as an effective
      therapy for patients with high-grade stenoses of the proximal limb arterial
      segments, (eg, the distal aorta, common iliac artery, or external iliac artery,
      and occasionally the proximal common femoral artery). Surgical revascularization
      usually is reserved for patients who present with severe aortoiliac disease in
      whom long-term patency is likely to be achieved (eg, aortobifemoral or femoral
      femoral bypass) and who have a low cardiovascular perioperative ischemic risk.
      Patients who undergo successful revascularization also are likely to benefit from
      exercise rehabilitation programs. All patients with PAD, of any severity, must
      successfully normalize atherosclerosis risk factors and use antiplatelet
      therapies. Such interventions include complete smoking cessation, glycemic
      control, normalization of blood pressure (less than 130/90 mm Hg), and lowering
      of low-density lipoprotein (LDL) cholesterol to less than 100 mg/dL. Antiplatelet
      agents (eg, clopidogrel, aspirin) should be prescribed to decrease rates of
      cardiovascular ischemic events in all patients with PAD, unless otherwise
      contraindicated.

PMID- 11341863
TI  - Embolism from the Aorta: Atheroemboli and Thromboemboli.
AB  - To date, there are no evidence-based data to support specific drug therapy for a
      patient with atheroembolism. It makes sense to use HMG CoA (3-hydroxy-3
      methylglutaryl coenzyme A) reductase inhibitors (statins) in any patient with
      atherosclerosis, as these drugs have been shown to reduce the risk of myocardial
      infarction and stroke, and have a theoretical benefit on plaque stabilization.
      Surgical treatment should be considered for patients with abdominal aortic or
      popliteal artery aneurysms and downstream atheroembolism. There are case reports
      of atheroemboli in patients worsening after given warfarin or heparin. For this
      reason, some institutions are reluctant to prescribe these drugs for patients
      with atheroemboli or thromboemboli from aortic plaque. However, the incidence of
      this complication is quite low. Anticoagulation probably should be stopped if a
      patient develops atheroembolism. Similarly, the current state of knowledge does
      not allow for selecting specific pharmacologic intervention in patients with
      thromboemboli from aortic plaque. Statin therapy does make sense, as these drugs
      theoretically stabilize plaques and prevent plaque hemorrhage, thrombosis, and
      subsequent embolization. Unstable aortic plaques may develop superimposed thrombi
      (red thrombi on pathologic examination), easily seen as mobile elements on
      transesophageal echocardiography. Therefore, it is possible that anticoagulation
      with warfarin might prevent embolic events in these patients. For this reason, we
      are often in the position of recommending warfarin therapy for patients with
      emboli and severe atheromas seen on transesophageal echocardiography, especially
      when superimposed mobile thrombi are seen. There are small series in the
      literature that indicate the potential benefit of warfarin. However, until a
      large multicenter randomized clinical trial is done, the use of warfarin can not
      be definitively recommended. Antiplatelet agents, although safer than warfarin
      (less risk of hemorrhage), have not been proven beneficial in patients with
      thromboembolism from the aorta. Surgery (endarterectomy) of the aortic arch is a
      very risky procedure that should not be performed routinely, but may be used in
      highly selected patients.

PMID- 11341864
TI  - Renal Artery Stenosis.
AB  - Renal artery stenosis (RAS) can accelerate or generate progressive hypertension
      and renal dysfunction. The goals for treating patients with RAS are to reduce
      cardiovascular morbidity and mortality attributable to elevated arterial pressure
      and to preserve renal function beyond critical stenosis. Recent, randomized
      trials with current antihypertensive agents indicate that many patients with RAS
      can be managed for years without renal artery revascularization. As it does
      elsewhere, atherosclerotic disease can progress to more severe occlusion in the
      renal arteries. Rapid advances in endovascular techniques, including stenting,
      make restoration of renal blood flow possible in more patients than before.
      Therapeutic goals are achieved by 1) avoidance of tobacco, 2) reducing arterial
      pressure with antihypertensive drug therapy, particularly those agents capable of
      blocking the renin-angiotensin system, and 3) renal revascularization, using
      balloon angioplasty and stent placement, surgical bypass, or endarterectomy. The
      major clinical challenges are to identify progressive occlusive disease and to
      determine appropriate timing for vascular intervention.

PMID- 11341865
TI  - Mesenteric Vascular Disease.
AB  - The clinical presentation of mesenteric ischemia depends on the site, grade, and
      cause of vascular obstruction; the degree of collateralization; and the stage of
      disease. Patients in the early stages of ischemia typically have abdominal pain
      out of context with an unimpressive abdominal examination. It is during this
      stage that medical and endovascular techniques can be most effective. After signs
      of peritonitis are present (signaling bowel infarction), surgical exploration and
      bowel resection are necessary. Chronic mesenteric ischemia induced by stenotic
      arteriosclerosis should be treated with percutaneous transluminal angioplasty and
      stenting (PTAS). Chronic mesenteric arterial occlusions are better handled with
      bypass surgery. Acute embolic or thrombotic ischemia is surgically treated after
      medical resuscitation. Endovascular techniques may be applicable in selected
      patients (usually in those with subacute symptoms), but thrombolytic therapy
      should be avoided if intestinal infarction is suspected. Non-occlusive mesenteric
      ischemia requires a rapid correction of the predisposing hypotension or sepsis
      followed by papaverine infusion into the superior mesenteric artery. Celiac
      artery compression syndrome requiring treatment is best treated with surgical
      release of the median arcuate ligament; PTAS should not be performed. Mesenteric
      venous occlusion should be treated with anticoagulation. Surgical exploration and
      bowel resection is necessary in patients presenting with acute signs and
      symptoms, reserving thrombolytic therapy for early, mildly symptomatic,
      thromboses in whom there is no contraindication to thrombolysis.

PMID- 11341866
TI  - Venous Thrombosis of the Upper Extremities.
AB  - The goals of treating patients with upper-extremity deep vein thrombosis (UEDVT)
      are to relieve acute symptoms of venous occlusion, prevent pulmonary embolism,
      reduce the likelihood of recurrent thrombosis, and avoid the development of
      postphlebitic syndrome. Although the details of management differ, depending on
      the underlying cause and precipitating factors, anticoagulant therapy should be
      the first-line treatment of choice in all cases. For patients with primary or
      idiopathic UEDVT (Paget-von Schroetter syndrome), aggressive measures including
      catheter-directed thrombolysis, vascular procedures (eg, balloon angioplasty,
      stenting, filter), and surgical maneuvers (eg, first rib resection) have been
      advocated by some surgeons, but none of these high-risk interventions has been
      evaluated properly in prospective controlled trials. In contrast, for patients
      with catheter-associated central venous thrombosis (CACVT), or other secondary
      cases of UEDVT, many clinicians simply withdraw the catheter and avoid
      anticoagulant therapy. Because well-designed clinical trials are lacking,
      recommendations about the management of UEDVT are derived from descriptive
      studies and case series. Until further research identifies the natural history
      and optimum management of UEDVT, it seems reasonable to base treatment on
      anticoagulant regimens with proven effectiveness in lower-extremity deep vein
      thrombosis (LEDVT). The use of additional intervention(s) should be reserved for
      carefully selected patients.

PMID- 11341867
TI  - Heparin-induced Thrombocytopenia.
AB  - Treatment with heparin is associated with two types of thrombocytopenia. The most
      worrisome of these is the immune-mediated heparin-induced thrombocytopenia (HIT
      type II). Suspicion of HIT type II mandates immediate cessation of heparin
      administration and consideration of an alternative anticoagulation therapy.
      Hirudin and argatroban are approved alternative anticoagulants with no cross
      reactivity with the HIT antibody. HIT type II is a clinicopathologic syndrome,
      and therefore diagnosis requires clinical and laboratory confirmation. The
      laboratory evaluation for HIT type II should also determine whether or not there
      is HIT-antibody cross-reactivity with danaparoid and low molecular weight
      heparin. Patients with HIT type II who require coronary artery bypass graft
      surgery present a particularly difficult situation, as there is no ideal
      alternative to heparin anticoagulation.

PMID- 11341868
TI  - Prophylaxis of Venous Thrombosis.
AB  - Mechanical measures such as graduated compression stockings and intermittent
      compression boots are available for venous thrombosis prophylaxis, but compliance
      may be limited. Plantar venous pneumatic compression devices have attained
      widespread acceptance by both patients and nurses because of their comfort and
      compact size, but their track record for efficacy is poor. Inferior vena cava
      filters prevent pulmonary embolism, but do not halt the thrombotic process or
      prevent venous thrombosis. Pharmacologic prophylaxis traditionally has relied
      upon minidose unfractionated heparin; however, re-examination is warranted in the
      face of increasingly ill and complex patients. My opinion is that small, fixed
      doses of once-daily low molecular weight heparin will eventually replace minidose
      unfractionated heparin as the standard pharmacologic prophylaxis regimen for most
      surgical and medical patients. Prolongation of prophylaxis after hospital
      discharge should receive increased emphasis. Most patients being transferred to a
      skilled nursing facility should receive venous thromboembolism prophylaxis.
      Similarly, most patients undergoing total hip or knee replacement should receive
      prolonged preventive regimens, with at least 1 month of anticoagulation. Despite
      advances, certain aspects of venous thrombosis prophylaxis remain problematic.
      First, a surprisingly high number of hospitalized patients develop venous
      thrombosis because of failed (rather than omitted) prophylaxis. Second, many
      patients in intensive care have a combination of peripheral vascular disease and
      active bleeding (usually gastrointestinal) that precludes mechanical or
      pharmacologic prophylaxis. Third, neurosurgical patients undergoing craniotomy
      for brain tumors suffer a high rate of venous thrombosis and major pulmonary
      embolism despite the routine use of combined mechanical and pharmacologic
      prophylaxis. My opinion is that these three areas, in addition to the hospital
      culture of prophylaxis, should receive increased attention in an effort to
      prevent venous thromboembolism.

PMID- 11341878
TI  - Postlicensure safety surveillance for varicella vaccine. Wise RP,*(1) Salive ME,
      Braun MM, Mootrey GT, Seward JF, Rider LG, Krause PR. JAMA 2000;284:1271-1279.

PMID- 11341869
TI  - Critical Limb Ischemia.
AB  - Patients with critical limb ischemia (CLI) present with ischemic rest pain or
      with tissue loss. Tissue loss, in its mildest presentation, includes focal
      ischemic ulceration or nonhealing wounds. Gangrene is the manifestation of severe
      chronic ischemia. Without revascularization, patients with CLI are at risk for
      limb loss and for potentially fatal complications from the progression of
      gangrene and the development of sepsis. The best patient outcomes are achieved
      when the diagnosis and appropriate treatment for CLI are not delayed. Simple
      noninvasive tests, such as measurement of ankle-to-brachial indices or toe
      Doppler pressures, take only minutes to provide sufficient information to confirm
      the diagnosis of peripheral artery disease (PAD) and to document the severity of
      limb ischemia. Subsequent diagnostic imaging studies, such as arteriography,
      magnetic resonance angiography, or ultrasound duplex scanning, provide the
      detailed information needed to plan revascularization therapy. Balloon
      angioplasty and stenting work best for focal segments of narrowing or short
      occlusions of the iliac arteries, but endovascular treatments yield progressively
      poorer results with longer and more distal lesions. Long segments of occlusion,
      especially those distal to the common femoral artery, are best treated with
      surgical bypass. Pharmacotherapy and adjunctive therapies, such as topical
      therapies or hyperbaric oxygen treatment, may have a limited role in patients in
      whom revascularization procedures have failed or for those in whom
      revascularization is not technically possible--particularly when amputation is
      the only alternative. Prostanoids are the best-studied class of drugs for such
      applications, but their use is still investigational in the United States. Though
      other medical approaches, such as use of other vasoactive agents, drugs that
      treat claudication, or gene-induced angiogenesis may prove useful, they do not
      yet have demonstrated roles in the treatment of patients with CLI.

PMID- 11341880
TI  - Long-term results of pneumatic retinopexy. Eter N,*(1) Boker T, Spitznas M.
      Graefes Arch Clin Exp Ophthalmol 2000;238:677-681.

PMID- 11341879
TI  - Evidence-based medicine: principles for applying the users' guides to patient
      care. Guyatt GH,*(1) Haynes RB, Jaeschke RZ, Cook DJ, Green L, Naylor CD, Wilson
      MC, Richardson WS for the Evidence-Based Medicine Working Group. JAMA
      2000;284:1290-1296.

PMID- 11341881
TI  - Intramuscular interferon beta-1a therapy initiated during a first demyelinating
      event in multiple sclerosis. Jacobs LD,*(1) Beck RW, Simon JH, Kinkel RP,
      Brownscheidle CM, Murray TJ, Simonian NA, Slasor PJ, Sandrock AW, and the CHAMPS
      Study Group. N Engl J Med 2000;343:898-904.

PMID- 11341882
TI  - Changes in optic nerve head blood flow and retrobulbar hemodynamics following
      calcium-channel blocker treatment of normal-tension glaucoma. Tomita G,*(1) Niwa
      Y, Shinohara H, Hayashi N, Yamamoto T, Kitazawa Y. Int Ophthalmol 1999;23: 3-10.

PMID- 11341883
TI  - Detection of gonioscopically occludable angles and primary angle closure glaucoma
      by estimation of limbal chamber depth in Asians: modified grading scheme. Foster
      PJ, Devereux JG, Alsbirk PH, Pak Lee PS, Uranchimeg D, Machin D, Johnson GJ,*(1)
      Baasanhu J. Br J Ophthalmol 2000;84:186-192.

PMID- 11341885
TI  - Effects of glaucoma medications on the cardiorespiratory and intraocular pressure
      status of newly diagnosed glaucoma patients. Waldock A,*(1) Snape J, Graham CM.
      Br J Ophthalmol 2000;84:710-713.

PMID- 11341884
TI  - Amniotic membrane transplantation for severe neurotrophic corneal ulcers. Chen H
      J, Pires RTF, Tseng SCG*(1). Br J Ophthalmol 2000;84:826-833.

PMID- 11341887
TI  - Mutations in MKKS cause obesity, retinal dystrophy and renal malformations
      associated with Bardet-Biedl syndrome. Katsanis N, Beals PL, Woods MO, Lewis RA,
      Green JS, Patfrey PS, Ansley SJ, Davidson WS, Lupski JR.*(1) Nat Gen 2000;26:67
      70.

PMID- 11341886
TI  - Myopia profile in Copenhagen medical students 1996-98. refractive stability over
      a century is suggested. Fledelius HC.*(1) Acta Ophthalmol Scand 2000;78:501-505.

PMID- 11341888
TI  - Human microphthalmia associated with mutations in the retinal homeobox gene
      CHX10. Percin EF, Ploder LA, Yu JJ, Arici K, Horsford DJ, Rutherford A, Bapat B,
      Cox DW, Duncan AMV, Kalnins VI, Kocak-Altintas A, Sowden JC, Trabousli E,
      Sarfarazi M, McInnes RR.*(1) Nat Gen 2000;25:397-401.

PMID- 11341889
TI  - Cyclin-dependent kinase inhibitory protein expression in human choroidal melanoma
      tumors. Mouriaux F,*(1) Maurage CA, Labalette P, Sablonniere B, Malecaze F,
      Darbon JM. Inv Ophthalmol Vis Sci 2000;41:2837-2843.

PMID- 11341890
TI  - Corrections.

PMID- 11341891
TI  - Corrections.

PMID- 11341892
TI  - Sclerostomy with an Erbium YAG Laser. The Relationship with Pulse Energy.
AB  - Purpose: To investigate the optimal pulse energy to do sclerostomy with an erbium
      YAG laser.Materials and Methods: The experiments were performed in enucleated
      porcine eyes. We changed pulse energy and examined the effects on surrounding
      tissue.Results: With the increase of pulse energy, the effects of the laser
      extended to the area surrounding the laser probe. At the threshold energy for
      doing full-thickness sclerostomy, the total energy was significantly higher than
      with higher pulse energy. And with pulse energy higher than 2 mJ, the total
      energy did not show any significant change. Histopathologically, the damaged area
      around sclerostomy became larger with the increase of pulse energy.Conclusion:
      The optimal energy to do full-thickness sclerostomy with this system seemed to be
      2 mJ.

PMID- 11341893
TI  - Effect of Antioxidants on Radical-initiated Peroxidation of Retinal Homogenate.
AB  - Purpose: To compare the effect of antioxidants on radical-initiated peroxidation
      of retinal homogenate.Methods: Lipid peroxides in bovine retinal homogenate were
      induced by 5 mM FeNO(3) (Fe), 25 mM 2, 2'-azobis(2, 4'-dimethylvaleronitrile)
      (lipid-soluble, AMVN) or 50 mM 2, 2'-azobis (2-amidinoprpane) dihydrochloride
      (water-soluble, AAPH) and the preventive effects of antioxidants were measured.
      Phosphatidylcholine hydroperoxide (PC-OOH) was analyzed with high performance
      liquid chromatography (HPLC) as the endpoint biomarker.Results and Conclusion:
      Troglitazone, an oral hypoglycemic agent, inhibited PC-OOH production by Fe and
      AMVN. Therefore, it may be effective for protecting against oxidative stress on
      the inner surface plasma membranes and subcellular organelle. Quercetin has
      radical scavenging effects on both sides of the membrane, because it prevents PC
      OOH production by AMVN or AAPH. These results demonstrate the usefulness of an in
      vitro screening test that can accurately and rapidly determine the capacity of an
      antioxidant against lipid peroxidation or oxidative stress. (Jpn Ophthalmol Soc
      104:466-70, 2000)

PMID- 11341894
TI  - Study on Collagen Viscoelastic Substance as an Auxiliary Agent in Anterior
      Segment Surgery. Ocular Irritation Study by Replace ment of the Aqueous Humor in
      Rabbits.
AB  - Purpose: Collagen solution was assessed as a possible visoelastic substance in
      anterior segment surgery, in terms of the depth of the anterior chamber and
      ocular irritation.Methods: The depth of the anterior chamber of enucleated rabbit
      eyes was evaluated 5 minutes after injection of collagen solution. For ocular
      irritation test, the aqueous humor of rabbits was replaced with collagen using
      sodium hyaluronate (HEALON((R))) and phosphate buffer (PB) as controls. Follow-up
      clinical examinations with hand-slit-lamp-microscopy, tonometry, pachymetry, and
      specular microscopy were performed for 7 days or 28 days, and then aqueous humor,
      corneal endothelium, and eye tissues were evaluated by gel electrophoresis,
      scanning electron microscopy, and light microscopy, respectively.Results: 2.5% to
      3% collagen solution was found to be optimal for maintaining the depth of the
      anterior chamber. No significant differences in clinical findings such as
      anterior chamber and corneal thickness or in biochemical and histological
      findings were observed among collagen-, hyaluronate- and PB-treated groups,
      except for intraocular pressure which was increased in the hyaluronate-treated
      group, but not in the collagen-treated group.Conclusion: Collagen specifically
      prepared for this study seems to be an excellent auxiliary agent for anterior
      segment surgery, providing an appropriate anterior chamber with little ocular
      irritation. (Jpn Ophthalmol Soc 104:458-65, 2000)

PMID- 11341895
TI  - Variables That Influence Visual Acuity After Macular Hole Surgery.
AB  - Purpose: To evaluate the variables that influence visual acuity and visual
      improvement after macular hole surgery.Methods: Our study included 421 eyes in
      which macular holes were successfully closed after surgery and followed up at
      least 1 year after the last surgery. Surgical techniques were conventional
      methods (Group 1: 350 eyes) with retinal pigment scalping of the macular hole
      basis added in the refractory cases (Group 2: 71 eyes). The variables used for
      the multiple regression were gender, age, preoperative visual acuity, hole stage,
      duration of symptoms, hole size, and axial length.Results: The variables that
      most influenced postoperative visual acuity were as follows: Group 1: gender (r =
      -0.011, P =.016), age (r = -0.17, P =.005), preoperative visual acuity (r = 0.51,
      P <.0001), duration of symptoms (r = -0.015, P <.0001), and axial length (r = 
      0.090, P =.045). Group 2: age (r = -0.18, P =.047), and preoperative visual
      acuity (r = 0.47, P <.0001).Conclusions: The variables that influenced visual
      acuity and visual improvement after macular hole surgery were common. In Group 1:
      gender, age, preoperative visual acuity, duration of symptoms, and axial length;
      in Group 2: age and preoperative visual acuity.

PMID- 11341896
TI  - Typing of Herpes Simplex Virus in Patients with Uveitis.
AB  - Aim: To examine the type of herpes simplex virus (HSV) in cases with
      uveitis.Materials and Methods: Intraocular fluid specimens obtained from 3 cases
      with herpetic iridocyclitis and 6 cases with acute retinal necrosis (ARN) were
      examined by polymerase chain reaction (PCR). HSV typing was performed by the
      restriction patterns of the PCR products. Serum samples obtained from these cases
      and 33 cases with uveitis were examined by neutralization test (NT) for the
      availability of the typing of HSV.Results: The restriction patterns of the PCR
      products amplified from 3 specimens of iridocyclitis revealed HSV type 1 DNA. HSV
      type 2 DNA was identified in 5 of 6 cases of ARN and HSV type 1 DNA was found in
      only one case. The results of serum NT titers correlated with the typing of the
      amplicons.Conclusions: In the cases studied, HSV type 1 was the dominant
      etiological agent in herpetic iridocyclitis, while HSV type 2 plated a similar
      role in HSV-associated ARN. The examination of the serum NT may be helpful for
      the identification of the etiological types of HSV in patients with uveitis.

PMID- 11341897
TI  - Incidence of Reopening and Variables That Influence Reopening After Macular Hole
      Surgery.
AB  - Purpose: To evaluate the incidence and variables of reopening of macular holes
      after macular hole surgery.Methods: Our study included 467 eyes in which macular
      holes were successfully closed after surgery. Surgical techniques consisted of
      conventional methods (358 eyes) and scalping methods (109 eyes) with retinal
      pigment scalping of the macular hole basis added in such cases: reoperation, hole
      size (more than 0.4 disc diameter), duration of symptoms (more than 2 years).
      Long term incidence of reopening was predicted by life table method. After we
      compared reopened cases with non-reopened cases, the variables of gender, stage,
      biocular occurrence, age, duration of symptoms, hole size, preoperative visual
      acuity, refraction axial length ratio, and intraoperative retinal tears were used
      for the multiple regression.Results: Reopening was found in 20 eyes (5.6%)
      treated by conventional methods and in 10 eyes (9.2%) treated by scalping
      methods. Survival ratio was 87% for the conventional methods in 6 years and 79%
      for the scalping methods in 5 years. The variables influencing reopening were as
      follows: conventional methods: gender (r = 0.065, P =.19), biocular occurrence (r
      = 0.12, P =.026), and refraction axial length ratio (r = -0.11, P =.045);
      scalping methods: hole size (r = 0.14, P =.25).Conclusions: Incidence of
      reopening in scalping methods was high. The variables that influenced reopening
      after macular hole surgery were biocular occurrence and refraction axial length
      ratio in conventional methods. The shape of the eye may be related to reopening.

PMID- 11341898
TI  - Factors Influencing Visual Acuity Following Vitrectomy for Exudative Age-related
      Macular Degeneration.
AB  - Purpose: We investigated the influence of various factors on visual results in
      patients undergoing surgical removal of choroidal neovascular membranes (CNVM)
      caused by age-related macular degeneration (AMD).Subjects and Methods: This study
      was performed in 55 eyes of 55 patients who underwent surgical removal of CNVM
      for AMD and followed them for 6 months or more. The criterion for surgical
      eligibility was active subfoveal choroidal neovascular membrane of 0.5 or more
      disc diameter above the retinal pigment epithelium with visual acuity of 0.3 or
      worse. We investigated the influence of various factors on the logarithm of the
      minimum angle of resolution (log MAR) final visual acuity. The factors were age,
      symptom duration, preoperative log MAR visual acuity, CNVM diameter, mean
      deviation with visual field analyzer, previous laser treatment, posterior
      vitreous detachment, findings of indocyanine green angiography, operative
      complications, and recurrence of CNVM.Results: Better preoperative visual acuity,
      shorter symptom duration, and smaller CNVM diameter were correlated with better
      postoperative final visual acuity.Conclusions: Surgical excision of subfoveal
      CNVM may be the better therapeutic choice in selected cases with AMD.

PMID- 11341899
TI  - Light and Electron Microscopic Study of the Retina in a Patient with Congenital
      Glaucoma.
AB  - Purpose: The morphological observation of the human retinal changes caused by
      severely elevated intraocular pressure (IOP) in congenital glaucoma.Method: Light
      and electron microscopy.Subjects: One eye of a 15-year-old boy diagnosed as
      having congenital glaucoma was obtained after he had suffered from severe visual
      disturbance and ocular pain because of extensive elevated IOP, corneal leucoma,
      and exophthalmos.Results: Ganglion cells and nerve fibers in the inner layer were
      lost and replaced by Muller cell processes. The cellular elements in the outer
      layer were regularly arranged, but these cytoplasmic organelles were not very
      well developed. Most of the cellular elements of the whole retina contained many
      dense bodies. The retinal capillaries in the nerve fiber layer were lost or
      severly damaged, but some of these in the inner plexiform layer were intact. In
      the retinal arteries and veins marked thickening of the adventitial tissues was
      observed. These tissues consisted of remarkably increased and irregularly
      arranged collagen fibers, and a few elastic fibers scattered in some
      parts.Conclusion: It appeared that the pathological changes in the inner layer of
      the retina were caused by ischemia. The retinal vascular abnormality was thought
      to be the result of protective reaction against the severly elevated IOP.

PMID- 11341900
TI  - Intracameral and Lenticular Penetration of Locally Applied Deuterium-Labeled
      Vitamin E in Rats.
AB  - Purpose: To confirm the intraocular dynamics of 1% deuterium (D) labeled alpha
      tocopheral acetate (VEA) solution.Methods: The concentrations of D(3)-VEA and
      D(3)-alpha-tocopherol (VE) derived from D(3)-VEA in the aqueous humor and lens
      were measured after instilling 1% D(3)-VEA continuously into the cul-de-sac of
      rat eyes for one and three weeks. D(3)-VEA and D(3)-VE concentrations were
      determined by gas chromatograph/mass spectrometry.Results: D(3)-VEA and D(3)-VE
      concentrations in the aqueous humor after one and three weeks of continuous
      administration were 93.1 and 498.9, and 9.4 and 21.5 ng/mL, respectively. The
      concentrations in the lens were 15.0 and 6.1, and 9.8 and 4.8 ng/g,
      respectively.Conclusion: The penetration of VEA into the aqueous humor and lens
      by eyedrop application was confirmed.

PMID- 11341901
TI  - Effect of Topically Applied Iganidipine Dihydrochloride, a Novel Ca(2+)
      Antagonist, on Optic Nerve Head Circulation in Rabbits.
AB  - Purpose: We studied the effect of topically applied iganidipine dihydrochloride,
      a novel water-soluble calcium channel blocker on the blood flow of optic nerve
      head (ONH), intraocular pressure, and blood pressure in rabbits.Methods: (1) 0.1%
      iganidipine (20 &mgr;l) was instilled into a normal eye. The change in blood flow
      in the ONH was measured using a hydrogen gas clearance flowmeter. (2) Iganidipine
      (0.0001%-0.1%) was instilled into a circulation-disordered eye before or after
      the intravitreal injection of endothelin-1, and change in the blood flow in the
      ONH was measured. (3) Changes in intraocular pressure and blood pressure after
      instillation of 0.1% iganidipine were measured. In all experiments, physiological
      saline was instilled in each contralateral eye as a control.Results: (1)
      Instillation of iganidipine significantly increased the blood flow in the ONH by
      40% at 45 minutes after instillation. (2) Pre-instillation of 0.01 and 0.1%
      iganidipine almost completely inhibited the decrease of blood flow in the ONH in
      the circulation-disordered model. The decrease of blood flow in the ONH was
      corrected with post-instillation of 0.1% iganidipine. These effects were
      continuous. (3) Instillation of 0.1% iganidipine did not change either
      intraocular pressure or blood pressure.Conclusion: It was shown that instillation
      of iganidipine continuously increased and maintained the blood flow in the ONH in
      normal and circulation-disordered rabbit eye models.

PMID- 11341902
TI  - The Effects of Aging on the Multifocal Electroretinogram.
AB  - Purpose: In order to use multifocal electroretinogram (m-ERG) for clinical
      assessment, we investigated the effects of aging on waves of the first and second
      order kernels of the m-ERG.Subjects and Methods: m-ERGs were recorded from 93
      eyes (refractive error 0 to -3. 0 D) of 56 normal subjects (range, 12-79, mean,
      44.2 +/- 20. 7 years of age) using the Visual Evoked Response Imaging System
      (VERIS Science((R)), version 3.0.1). We analyzed effects of aging on the response
      densities and the peak latencies of the first positive wave (P 1) of the first
      order kernel and the second and third positive waves (P 2 and P 3) of the second
      order kernel.Results: The response densities of the P 1 and P 2 waves
      significantly decreased, and the peak latencies of the P 1, P 2 and P 3 were
      significantly prolonged (P < 0.05) in the subjects above 50 years old.Conclusion:
      The results suggested that the aging effect on the m-ERG should be considered
      when evaluating retinal function using m-ERGs in basic and clinical studies.

PMID- 11341903
TI  - Refraction and Anterior Chamber Depth Change After Vitrectomy for Pseudophakia.
AB  - Purpose: To evaluate the association between the vitreous and the refractive
      error in pseudophakia.Methods: Vitrectomy was performed in 67 eyes of 61 patients
      who underwent cataract surgery. Vitrectomy was needed for epiretinal membrane in
      30 eyes, macular edema in 22 eyes, macular hole in 3 eyes, lamelar macular hole
      in 2 eyes, macular hole in 3 eyes, lamelar macular hole in 2 eyes, vitreous
      opacity in 6 eyes, and vitreous hemorrhage in 4 eyes. Refraction was measured
      before the operation, and 1 month, 3 months, 6 months, and 12 months after
      operation. Anterior chamber depth was measured in 10 eyes before the operation,
      and 1 month, 3 months, and 6 months after operation. We evaluated the refractive
      error after vitrectomy in 49 eyes that had predicted refraction.Results: The mean
      value of refractive change was -0.3 D 1 month postoperatively, and then gradually
      became positive. The variation of refraction (6-month postoperative refraction
      minus preoperative refraction) was negatively correlated with preoperative
      refraction (P =.0052, R(2) = 0.146). If preoperative refraction was more myopic
      than -1.5 D, then refraction became positive. If preoperative refraction was not
      more myopic than -1.5 D, then refraction became negative.Conclusion: About 15% of
      postoperative refractive error may be associated with the vitreous, but further
      investigation is required.

PMID- 11341904
TI  - Scanning Laser Ophthalmoscopic Microperimetry on Idiopathic Epiretinal Membrane
      and Vitreomacular Traction Syndrome.
AB  - Purpose: To evaluate visual function before and after vitrectomy for idiopathic
      epiretinal membrane and vitreomacular traction syndrome.Methods: Microperimetry
      with scanning laser ophthalmoscope (SLO) was performed in 4 eyes with idiopathic
      epiretinal membrane (IERM) and 2 eyes with vitreomacular traction syndrome
      (VMTS), before and at least 3 months after vitrectomy.Results: Five eyes had
      preoperative scotoma, which disappeared postoperatively. In 1 eye, absolute and
      relative scotomas developed postoperatively over the areas where the retinal
      surface was vigorously scratched to peel off an overlying membrane, and in
      another eye new scatomas appeared over a newly formed epiretinal membrane 8
      months after vitrectomy.Conclusions: To our knowledge, the present report is the
      first to describe preoperative absolute scotoma in IERM, VMTS and also iatrogenic
      absolute scotoma due to retinal scratching. SLO microperimetry is useful for
      evaluation of visual function before and after vitrectomy for epiretinal membrane
      and vitreomacular traction syndrome.

PMID- 11341905
TI  - Bacterial Infection in the Conjunctiva of Patients with Adenoviral
      Conjunctivitis.
AB  - Purpose: We evaluate the microbiological features of mixed infection in
      adenovirus-infected conjunctiva.Subjects: Isolation of bacteria was performed in
      82 samples of adenoviral conjunctivitis at six eye clinics in Japan.Methods: For
      microbiological diagnosis, we performed immunochromatography (IC) and polymerase
      chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis for
      detection and serotyping of adenovirus, and PCR for detection of herpes simplex
      virus (HSV) and Chlamydia trachomatis antigens out of 82 samples with adenoviral
      conjunctivitis.Results: Pathogenic bacteria were isolated in 6 samples out of 82.
      Out of these 6 cases, 5 samples were gram-negative rods and most of them were
      Flavobacterium meningosepticum (4 samples). Adenovirus type 8 was isolated from
      all these mixed infection cases. However, HSV-1 and Chlamydia trachomatis were
      not found.Conclusions: From these results, it is suggested that gram-negative
      rods, especially F. meningosepticum, are the most common bacteria causing mixed
      bacterial infection in adenoviral conjunctivitis.

PMID- 11341906
TI  - Investigation of Corneal Autofluorescence in Diabetic Patients.
AB  - Purpose: The investigation of corneal autofluorescence in diabetic
      patients.Objects and Methods: Corneal autofluorescence was investigated with a
      newly-developed fluorophotometer (wave length: excitation, 290-390 nm; emission,
      430-630 nm) having, fluorescence characteristics involving those of reduced
      pyridine nucleotides (PN) and advanced glycation endoproduct (AGE) except
      pentosidine and pyrraline. Twenty-eight patients with non-insulin-dependent
      diabetes mellitus and sixty-seven healthy volunteers were studied.Results: The
      corneal autofluorescence was 1.65 times higher than that of controls (P <.0001).
      In non-insulin-dependent diabetes mellitus, the corneal autofluorescenece was not
      correlated significantly with various diabetic parameters in blood (r < 0.4). In
      controls, the corneal autofluorescence was correlated significantly with age (r =
      0.438).Conclusion: The corneal autofluorescence has some relation with PN and AGE
      accumulation in the cornea.

PMID- 11341907
TI  - Quantitative Analysis of Indocyanine Green Angiographic Image in Central Serous
      Chorioretinopathy.
AB  - Purpose: To disclose the possible involvement of choroidal vascular change in
      developement of central serous chorioretinopathy (CSC).Methods: Indocyanine green
      (ICG) angiography was performed in 31 eyes with acute CSC, and 21 eyes from
      normal subjects. The maximum diameter of the choroidal veins and intensity of
      background fluorescence in the posterior fundus with ICG video images were
      measured for further analysis using IMAGEnet((R)) (Topcon). Then the results from
      CSC affected eyes, their fellow eyes, and normal eyes were compared. Aging
      factors were taken into consideration when we analyzed the data.Result: The
      maximum diameters of the choroidal veins were larger in both affected and fellow
      eyes than in the normal eyes (P <.001), and had a positive correlation with aging
      particularly in fellow eyes (r = 36). Both in the affected and fellow eyes, the
      background fluorescein intensity in the posterior pole of the late phase images
      was lower than in the normal eyes (P <.001), and was correlated with aging (r =
      0.28, r = 0.43).Conclusion: This quantitative study showed that choroidal venous
      dilatation and the residual background fluorescence in the posterior fundus might
      be positive findings reflecting the pathogenesis of CSC.

PMID- 11341908
TI  - Binocular Function of Intermittent Exotropia Before and After Surgery.
AB  - Purpose: We examined the binocular function of intermittent exotropia before and
      after surgery, and studied the effect of the surgery and the factor that might be
      involved in its result.Materials and Methods: 402 intermittent exotropic
      patients, who underwent their first surgical correction for the strabismus at
      Teikyo University Hospital, were examined for retinal correspondence and stereo
      acuity before and after surgery.Results: 367 patients (91.3%) had already had
      good stereo acuity before surgery when their eyes were straight. Regarding
      retinal correspondence, though 192 patients (47.8%) were abnormal (dual) before
      surgery, 301 patients (74.9%) were normal after surgery. The eye deviation of 101
      patients who could not get normal retinal correspondence after surgery was
      significantly larger than normal (P <.001), and 77.2% of them had also vertical
      strabismus which was mainly composed of dissociated vertical
      deviation.Conclusion: Normal binocular function could be recovered by surgical
      treatment in most intermittent exotropic patients. When patients could not get
      normal retinal correspondence after surgery, we supposed that dissociated
      vertical deviation might exert an important effect upon their binocular function.

PMID- 11341909
TI  - One Case of Harada Disease Complicated by Acute Posterior Multifocal Placoid
      Pigment Epitheliopathy-like Recurrence in Both Eyes.
AB  - Background: We encountered a patient who developed serous retinal detachment in
      one eye first, subsequently showed multiple small subretinal punctated opacity
      looking like acute posterior multifocal placoid pigment epitheliopathy (APMPPE)
      in both eyes, and had repeated recurrence.Case: A 28-year-old female presented
      with serous retinal detachment accompanied by multifocal small subretinal white
      punctated opacity at the posterior pole of the fundus in the left eye.
      Fluorescein angiography (FAG) revealed many small punctated hypofluorescent
      lesions scattered all over the eye in the early stage and multiple subretinal
      spotty leakage of fluorescein, subretinal accumulation of dye, and leakage of
      fluorescein from the optic disc in the late stage. Indocyanine green angiography
      (ICG) revealed small punctated hypofluorescent lesions from the early to late
      stage in both eyes. The disease recurred five and a half months after, and there
      appeared many yellowish white round opaque parts and serous retinal detachment at
      the posterior pole in both eyes. FAG showed a reversal phenomenon of fluorescein
      in both eyes. On ICG many small punctated hypofluorescent lesions were noted and
      in the late stage insular faint hypofluorescence consistent with serous retinal
      detachment, light tissue stain and fluorescent leakage in the center of the
      hypofluorescent lesion were also found. The disease recurred three times
      thereafter. At present, about two years after the first medical examination, the
      fundus does not show any sunset glow-like fundus, and vision of 1.2 is maintained
      on the right and left.Conclusion: A rare case of Harada disease complicated with
      APMPPE-like recurrence is presented.

PMID- 11341910
TI  - Study on the Progression of Visual Field Defect and Clinical Factors in Normal
      Tension Glaucoma.
AB  - Purpose: We investigated the relationship between the progression of visual field
      defect and clinical factors in patients with normal-tension glaucoma
      (NTG).Subjects and Methods: Forty-eight eyes of 48 NTG patients undergoing more
      than 5-year follow-up were enrolled in this study. Their visual field defects
      ranged between Aulhorn's classification stage 2 and 4, and mean deviation (MD)
      more than -10 dB measured by Humphrey Field Analyzer (HFA). End points of this
      follow-up study were defined as follows: in HFA STATPAC 2 glaucoma change
      probability analysis, more than 5 points which significantly deteriorated at P
      <.05 were found at 2 consecutive examinations (Criterion 1) or a significant
      decrease in MD value at P <.025 was encountered at one examination or in MD value
      at P <.05 at consecutive examinations (Criterion 2).Results: During the follow-up
      period, 18 eyes of 48 patients satisfied Criterion 1 and 21 eyes Criterion 2.
      There were no significant differences in clinical factors between patients with
      progression and without progression. By multiple logistic regression analysis,
      minimum flow velocity of central retinal artery (CRA) showed significant relation
      (odds ratio for a 1 cm/sec rise = 0.2215; 95% confidence interval: 0.0530-0.9253)
      to progression of visual field defect in Criterion 1, and minimum flow velocity
      of CRA (odds ratio for a 1 cm/sec rise = 0.2099; 95% confidence interval: 0.0506
      0.8712) and cholesterol (odds ratio for a 1 cm/dl rise = 1.0332; 95% confidence
      interval: 0.4096-2.6064) showed significant relation in Criterion 2.Conclusion:
      These results suggests that vascular risk factors of ocular blood flow may play a
      role in the progression of visual field defects in NTG patients.

PMID- 11341911
TI  - Structure of cytochrome c oxidase: a comparison of the bacterial and
      mitochondrial enzymes.
AB  - It has been almost 5 years since the first structures of cytochrome c oxidase,
      from Paracoccus denitrificans and bovine heart mitochondria, were revealed. Since
      then many different proton pumping mechanisms have been proposed for the enzyme;
      however, no definitive conclusion has been achieved. In this article, we revisit
      the original structures of bacterial and mitochondrial oxidases and try to
      clarify similarities as well as differences between the two structures.

PMID- 11341912
TI  - Contribution of an aspartate residue, D114, in the active site of clostridial
      glutamate dehydrogenase to the enzyme's unusual pH dependence.
AB  - Glutamate dehydrogenase from Clostridium symbiosum displays unusual kinetic
      behaviour at high pH when compared with other members of this enzyme family.
      Structural and sequence comparisons with GDHs from other organisms have indicated
      that the Asp residue at position 114 in the clostridial enzyme may account for
      these differences. By replacing this residue by Asn, a mutant protein has been
      created with altered functional properties at high pH. This mutant protein can be
      efficiently overexpressed in Escherichia coli, and several criteria, including
      mobility in non-denaturing electrophoresis, circular dichroism (CD) spectra and
      initial crystallisation studies, suggest a folding and an assembly comparable to
      those of the wild-type protein. The D114N mutant enzyme shows a higher optimum pH
      for activity than the wild-type enzyme, and both CD data and activity
      measurements show that the distinctive time-dependent reversible conformational
      inactivation seen at high pH in the wild-type enzyme is abolished in the mutant.

PMID- 11341913
TI  - Kinetic evidence for surface residues influencing the active site of Coprinus
      cinereus peroxidase: analysis of the pH dependence of G154E, P90H and P90H-G154E
      substrate entrance mutants.
AB  - Three mutants of Coprinus cinereus peroxidase (CIP) were made to mimic the
      substrate entrance histidine 82-glutamic acid 146 pair of the substrate channel
      in lignin peroxidase (LIP). Compound I formation of LIP has a low pH optimum
      around pH 3, while optimal formation of CIP compound I is obtained at pH 6-11.
      The mutants were glycine 154-->glutamic acid (G154E), proline 90-->histidine
      (P90H) and the double mutant P90H-G154E. All three showed kinetics of compound I
      formation similar to that of wt CIP between pH 3 and 9. However, the stability of
      compound I was strongly affected by these mutations. In wt CIP compound I is
      stable for approximately 30 min, while compound I of the mutants were stable for
      5 s or less. The P90H and P90H-G154E mutants showed pK(a) values for the alkaline
      transition at least one pH unit lower than for wt CIP and the G154E mutant. We
      suggest that the changed electrostatic field results in destabilisation of the
      oxidised heme in compound I and II and that the P90H residue increases the
      electrostatic potential in the distal cavity thereby decreasing the pK(a) for the
      alkaline transition.

PMID- 11341914
TI  - Characterization of yeast homoserine dehydrogenase, an antifungal target: the
      invariant histidine 309 is important for enzyme integrity.
AB  - Fungal homoserine dehydrogenase (HSD) is required for the biosynthesis of
      threonine, isoleucine and methionine from aspartic acid, and is a target for
      antifungal agents. HSD from the yeast Saccharomyces cerevisiae was overproduced
      in Escherichia coli and 25 mg of soluble dimeric enzyme was purified per liter of
      cell culture in two steps. HSD efficiently reduces aspartate semialdehyde to
      homoserine (Hse) using either NADH or NADPH with kcat/Km in the order of 10(6-7)
      M(-1) x s(-1) at pH 7.5. The rate constant of the reverse direction (Hse
      oxidation) was also significant at pH 9.0 (kcat/Km approximately 10(4-5) M(-1) x
      s(-1)) but was minimal at pH 7.5. Chemical modification of HSD with diethyl
      pyrocarbonate (DEPC) resulted in a loss of activity that could be obviated by the
      presence of substrates. UV difference spectra revealed an increase in absorbance
      at 240 nm for DEPC-modified HSD consistent with the modification of two
      histidines (His) per subunit. Amino acid sequence alignment of HSD illustrated
      the conservation of two His residues among HSDs. These residues, His79 and
      His309, were substituted to alanine (Ala) using site directed mutagenesis. HSD
      H79A had similar steady state kinetics to wild type, while kcat/Km for HSD H309A
      decreased by almost two orders of magnitude. The recent determination of the X
      ray structure of HSD revealed that His309 is located at the dimer interface [B.
      DeLaBarre, P.R. Thompson, G.D. Wright, A.M. Berghuis, Nat. Struct. Biol. 7 (2000)
      238-244]. The His309Ala mutant enzyme was found in very high molecular weight
      complexes rather than the expected dimer by analytical gel filtration
      chromatography analysis. Thus the invariant His309 plays a structural rather than
      catalytic role in these enzymes.

PMID- 11341915
TI  - Homoserine dehydrogenase from Saccharomyces cerevisiae: kinetic mechanism and
      stereochemistry of hydride transfer.
AB  - Homoserine dehydrogenase (HSD), which is required for the synthesis of threonine,
      isoleucine and methionine in fungi, is a potential target for novel antifungal
      drugs. In order to design effective inhibitors, the kinetic mechanism of
      Saccharomyces cerevisiae HSD and the stereochemistry of hydride transfer were
      examined. Product inhibition experiments revealed that yeast HSD follows an
      ordered Bi Bi kinetic mechanism, where NAD(P)H must bind the enzyme prior to
      aspartate semialdehyde (ASA) and homoserine is released first followed by
      NAD(P)+. H-(1,2,4-triazol-3-yl)-D,L-alanine was an uncompetitive inhibitor of HSD
      with respect to NADPH (K(ii)=3.04+/-0.18 mM) and a noncompetitive inhibitor with
      respect to ASA (K(is)=1.64+/-0.36 mM, K(ii)=3.84+/-0.46 mM), in agreement with
      the proposed substrate order. Both kinetic isotope and viscosity experiments
      provided evidence for a very rapid catalytic step and suggest nicotinamide
      release to be primarily rate limiting. Incubation of HSD with stereospecifically
      deuterated NADP[2H] and subsaturating amounts of aspartate semialdehyde revealed
      that the pro-S NADPH hydride is transferred to the aldehyde. The pH dependence of
      steady state kinetic parameters indicate that ionizable groups with basic pKs may
      be involved in substrate binding, consistent with the observation of Lys223 at
      the enzyme active site in the recently determined 3D structure [B. DeLaBarre,
      P.R. Thompson, G.D. Wright, A.M. Berghuis, Nat. Struct. Biol. 7 (2000) 238-244].
      These findings provide the requisite foundation for future exploitation of fungal
      HSD in inhibitor design.

PMID- 11341916
TI  - Cloning, expression and some properties of alpha-carbonic anhydrase from
      Helicobacter pylori.
AB  - The alpha-carbonic anhydrase gene from Helicobacter pylori strain 26695 has been
      cloned and sequenced. The full-length protein appears to be toxic to Escherichia
      coli, so we prepared a modified form of the gene lacking a part that presumably
      encodes a cleavable signal peptide. This truncated gene could be expressed in E.
      coli yielding an active enzyme comprising 229 amino acid residues. The amino acid
      sequence shows 36% identity with that of the enzyme from Neisseria gonorrhoeae
      and 28% with that of human carbonic anhydrase II. The H. pylori enzyme was
      purified by sulfonamide affinity chromatography and its circular dichroism
      spectrum and denaturation profile in guanidine hydrochloride have been measured.
      Kinetic parameters for CO2 hydration catalyzed by the H. pylori enzyme at pH 8.9
      and 25 degrees C are kcat=2.4x10(5) s(-1), KM=17 mM and kcat/KM=1.4x10(7) M(-1) x
      s(-1). The pH dependence of kcat/KM fits with a simple titration curve with
      pK(a)=7.5. Thiocyanate yields an uncompetitive inhibition pattern at pH 9
      indicating that the maximal rate of CO2 hydration is limited by proton transfer
      between a zinc-bound water molecule and the reaction medium in analogy to other
      forms of the enzyme. The 4-nitrophenyl acetate hydrolase activity of the H.
      pylori enzyme is quite low with an apparent catalytic second-order rate constant,
      k(enz), of 24 M(-1) x s(-1) at pH 8.8 and 25 degrees C. However, with 2
      nitrophenyl acetate as substrate a k(enz) value of 665 M(-1) x s(-1) was obtained
      under similar conditions.

PMID- 11341917
TI  - Thermal inactivation of the plasma membrane H+-ATPase from Kluyveromyces lactis.
      Protection by trehalose.
AB  - The activity of the isolated plasma membrane H+-ATPase from Kluyveromyces lactis
      was measured during incubation at 35-45 degrees C and in the absence or in the
      presence of 0-0.6 M trehalose. As the temperature of incubation was raised from
      35 to 45 degrees C, increasing enzyme inactivation rates were observed. Thermal
      inactivation kinetics of the H+-ATPase were biphasic exhibiting a first rapid
      phase and then a second slow phase. The transition from the native state occurred
      through a temperature-mediated increase in the inactivation rate constants of
      both phases. A model is proposed where the native H+-ATPase yields a partially
      active intermediary during the first phase of inactivation and then the
      intermediary is slowly converted into a totally inactive enzyme in the second
      phase. At each of these temperatures trehalose protected the enzymatic activity
      in a concentration dependent manner. Full protection was observed at 0.6 M
      trehalose in the range of 35-40 degrees C. Whereas, at 42 and 45 degrees C, the
      trehalose-mediated thermoprotection of the H+-ATPase was only partial. Trehalose
      stabilized the enzyme mainly by preventing the temperature dependent increase of
      the first and second inactivation rate constants.

PMID- 11341918
TI  - Interaction of Escherichia coli purine nucleoside phosphorylase (PNP) with the
      cationic and zwitterionic forms of the fluorescent substrate N(7)
      methylguanosine.
AB  - Steady-state and time-resolved fluorescence spectroscopy, and enzyme kinetics,
      were applied to study the reaction of purine nucleoside phosphorylase (PNP) from
      Escherichia coli with its substrate N(7)-methylguanosine (m7Guo), which consists
      of an equilibrium mixture of cationic and zwitterionic forms (pK(a)=7.0), each
      with characteristic absorption and fluorescence spectra, over the pH range 6-9,
      where absorption and intrinsic fluorescence of the enzyme are virtually
      unchanged. The pH-dependence of kinetic constants for phosphorolysis of m7Guo
      were studied under condition where the population of the zwitterion varied from
      10% to 100%. This demonstrated that, whereas the zwitterion is a 3- to 6-fold
      poorer substrate, if at all, than the cation for the mammalian enzymes, both
      ionic species are almost equally good substrates for E. coli PNP. The imidazole
      ring-opened form of m7Guo is neither a substrate nor an inhibitor of
      phosphorolysis. Enzyme fluorescence quenching, and concomitant changes in
      absorption and fluorescence spectra of the two ionic species of m7Guo on binding,
      showed that both forms are bound by the enzyme, the affinity of the zwitterion
      being 3-fold lower than that of the cation. Binding of m7Guo is bimodal, i.e., an
      increase in ligand concentration leads to a decrease in the association constant
      of the enzyme-ligand complex, typical for negative cooperativity of enzyme-ligand
      binding, with a Hill constant <1. This is in striking contrast to interaction of
      the enzyme with the parent Guo, for which the association constant is independent
      of concentration. The weakly fluorescent N(7)-methylguanine (m7Gua), the product
      of phosphorolysis of m7Guo, is a competitive non-substrate inhibitor of
      phosphorolysis (K(i)=8+/-2 microM) and exhibits negative cooperativity on binding
      to the enzyme at pH 6.9. Quenching of enzyme emission by the ligands is a static
      process, inasmuch as the mean excited-state lifetime, <tau>=2.7 ns, is unchanged
      in the presence of the ligands, and the constants K(SV) may therefore be
      considered as the association constants for the enzyme-ligand complexes. In the
      pH range 9.5-11 there is an instantaneous reversible decrease in PNP emission of
      approximately 15%, corresponding to one of the six tyrosine residues per subunit
      readily accessible to solvent, and OH- ions. Relevance of the overall results to
      the mechanism of phosphorolysis, and binding of substrates/inhibitors is
      discussed.

PMID- 11341919
TI  - Interaction of Cu2+ ion with milk xanthine oxidase.
AB  - The interaction of Cu2+ ion with milk xanthine oxidase (XO) has been studied by
      optical spectroscopy, circular dichroism, ESR and transient kinetic techniques.
      It is observed that XO forms optically observable complexes with Cu2+ ion. The pH
      dependence studies of the formation of Cu2+-XO complex by optical spectroscopy
      and circular dichroism show that at least one ionizable group may be responsible
      for the formation of the complex. The EPR studies show that Cu2+ ion binds to XO
      with sulfur and nitrogenous ligands. The transient kinetic study of the
      interaction of Cu2+ with XO shows the existence of two Cu2+ bound XO complexes
      formed at two different time scales of the interaction, one at < or =5 ms and the
      other one at around 20 s. The complex formed at longer time scale may be
      responsible for the inhibition of the enzyme activity.

PMID- 11341920
TI  - Complement C4bC2 complex formation: an investigation by surface plasmon
      resonance.
AB  - Complex formation between the human complement proteins C4b and C2 was
      investigated by surface plasmon resonance. C4b was immobilised and C2 was used in
      the fluid phase to measure interaction at different ionic strengths (30-830 mM
      NaCl) and in the absence and presence of MgCl2. Maximum binding was observed at
      30 mM NaCl, and was negligible above 300 mM NaCl. Binding was not greatly
      influenced by variation in Mg(2+) in the range of 2.5-15 mM. C4bC2 affinity (Kd)
      was determined by steady-state analysis to be 7.2x10(-8) M in physiological
      conditions (10 mM Hepes, 2.5 mM MgCl2, 0.75 mM CaCl2 and 140 mM NaCl, pH 7.4).
      For C4(H2O)C2 complex formation, a Kd of 4.0x10(-8) M was calculated. As far as
      detected by the applied method, complex formation does not involve conformational
      changes of one of the binding partners. Consistent with previous reports, C4bC2
      binding takes place as a multiple-site binding event in the presence of Mg2+.
      C4bC2 complex formation in 10 mM Hepes, 2.5 mM EDTA and 140 mM NaCl (pH 7.4) was
      also observed and the interaction showed characteristics of a single-site binding
      event. Kd was 1.5x10(-8) M. Complement factor B (FB) was also tested for its
      binding to immobilised C4b. Weak interaction was observed at FB concentrations in
      the physiological range (500-1000 nM). Kd was 1.2x10(-6) M, indicating possible
      cross-reactivity between classical and alternative pathways of the activation of
      the complement system.

PMID- 11341921
TI  - Substrate specificity of human cathepsin D using internally quenched fluorescent
      peptides derived from reactive site loop of kallistatin.
AB  - Kallistatin, a serpin that specifically inhibits human tissue kallikrein, was
      demonstrated to be cleaved at the Phe-Phe bond in its reactive site loop (RSL) by
      cathepsin D. Internally quenched fluorescent peptides containing the amino acid
      sequence of kallistatin RSL were highly susceptible to hydrolysis by cathepsin D.
      Surprisingly, these peptides were efficiently hydrolyzed at Phe-Phe bond, despite
      having Lys and Ser at P2 and P2' positions, respectively, which was reported to
      be very unfavorable for substrates for cathepsin D. Due to the importance of
      cathepsin D in several physiological and pathological processes, we took the
      peptide containing kallistatin RSL sequence, Abz-Ala-Ile-Lys-Phe-Phe-Ser-Arg-Gln
      EDDnp, as a reference substrate for a systematic specificity study of S3 to S3'
      protease subsites (EDDnp=N-[2,4-dinitrophenyl]-ethylenediamine and Abz=ortho
      amino benzoic acid). We present in this paper some internally quenched
      fluorescent peptides that were efficient substrates for cathepsin D. They
      essentially differ from other previously described substrates by their higher
      kcat/Km values due, mainly, to low Km values, such as the substrate Abz-Ala-Ile
      Ala-Phe-Phe-Ser-Arg-Gln-EDDnp (Km=0.27 microM, kcat=16.25 s(-1), kcat/Km=60185
      microM(-1) x s(-1)).

PMID- 11341922
TI  - Regulation of skeletal muscle AMP deaminase: lysine residues are critical for the
      pH-dependent positive homotropic cooperativity behaviour of the rabbit enzyme.
AB  - Reaction of rabbit skeletal muscle AMP deaminase with a low molar excess of
      trinitrobenzene sulfonic acid (TNBS) results in conversion of the enzyme into a
      species with about six trinitrophenylated lysine residues per molecule which no
      longer manifests positive homotropic cooperativity at pH 7.1 or at the optimal pH
      value of 6.5 in the presence of low K+ concentrations. Substitution of the
      reactive thiol groups with 5,5'-dithiobis-(2-nitrobenzoic acid) does not protect
      the enzyme from the TNBS-induced changes of the catalytic properties, indicating
      that cysteine residues modification is not at the basis of the effects of TNBS
      treatment on AMP deaminase and strongly suggesting the obligatory participation
      of lysine residues to the constitution of a regulatory anionic site to which AMP
      must bind to stimulate the enzyme at alkaline pH. The TNBS-treated enzyme is also
      completely desensitized to inhibition by ATP, but not to inhibition by GTP and
      stimulation by ADP. This observation suggests a connection between the operation
      of the hypothesized anionic activating site, responsible for positive homotropic
      cooperativity, and the inhibition exerted by anionic compounds that compete for
      the same site, among them the most efficient metabolite being probably ATP.

PMID- 11341923
TI  - Electrospray ionization mass spectrometry, circular dichroism and SAXS studies of
      the (S)-hydroxynitrile lyase from Hevea brasiliensis.
AB  - We report on experiments pertaining to solution properties of the (S)
      hydroxynitrile lyase from Hevea brasiliensis (HbHNL). Small angle X-ray
      scattering unequivocally established the enzyme to occur in solution as a dimer,
      presumably of the same structure as in the crystal. The acid induced,
      irreversible deactivation of HbHNL was examined by electrospray ionization mass
      spectrometry (ESI-MS), circular dichroism (CD) and by measuring the enzyme
      activity. The deactivation is paralleled by an unfolding of the enzyme. ESI-MS of
      this 30000 Da per monomer heavy protein demonstrated that unfolding took place in
      several stages which are paralleled by a decrease in enzyme activity. Unfolding
      can also be observed by CD spectroscopy, and there is a clear correlation between
      enzyme activity and unfolding as detected by ESI-MS and CD.

PMID- 11341924
TI  - Replacement of Lys-75 of calmodulin affects its interaction with smooth muscle
      caldesmon.
AB  - The interaction of smooth muscle caldesmon with synthetic calmodulin (SynCam) and
      its five mutants with replacement of Lys-75 was analyzed by means of intrinsic
      Trp fluorescence, zero-length crosslinking and by caldesmon-induced inhibition of
      actomyosin ATPase activity. SynCam and its double mutant with replacement K75P
      and simultaneous insertion of KGK between residues 80 and 81 have a comparably
      low affinity to caldesmon and the probability of crosslinking of this mutant to
      caldesmon was the lowest among all mutants analyzed. SynCam and its double mutant
      (K75P+KGK) induced nearly complete reversion of caldesmon inhibition of
      actomyosin ATPase activity with half-maximal reversion achieved at about 1
      microM. Two mutants, K75A and K75V, with partially stabilized less positive
      central domain have higher affinity to caldesmon. These mutants induce 80-85%
      reversion of caldesmon inhibition of actomyosin ATPase and the half-maximal
      reversion was achieved at about 0.3-0.4 microM. Two last mutants, K75P and K75E,
      with distorted central domain have high affinity to caldesmon and the probability
      of crosslinking of K75P to caldesmon was the highest among calmodulin mutants
      tested. These mutants induced complete reversion of caldesmon inhibition with
      half-maximal effect observed at 0.3-0.4 microM. We suggest that the length,
      flexibility and charge of the central domain affect binding of calmodulin mutants
      and their ability to reverse caldesmon-induced inhibition of actomyosin ATPase
      activity.

PMID- 11341925
TI  - Xanthine dehydrogenase from Pseudomonas putida 86: specificity, oxidation
      reduction potentials of its redox-active centers, and first EPR characterization.
AB  - Xanthine dehydrogenase (XDH) from Pseudomonas putida 86, which was induced 65
      fold by growth on hypoxanthine, was purified to homogeneity. It catalyzes the
      oxidation of hypoxanthine, xanthine, purine, and some aromatic aldehydes, using
      NAD+ as the preferred electron acceptor. In the hypoxanthine:NAD+ assay, the
      specific activity of purified XDH was 26.7 U (mg protein)(-1). Its activity with
      ferricyanide and dioxygen was 58% and 4%, respectively, relative to the activity
      observed with NAD+. XDH from P. putida 86 consists of 91.0 kDa and 46.2 kDa
      subunits presumably forming an alpha4beta4 structure and contains the same set of
      redox-active centers as eukaryotic XDHs. After reduction of the enzyme with
      xanthine, electron paramagnetic resonance (EPR) signals of the neutral FAD
      semiquinone radical and the Mo(V) rapid signal were observed at 77 K. Resonances
      from FeSI and FeSII were detected at 15 K. Whereas the observable g factors for
      FeSII resemble those of other molybdenum hydroxylases, the FeSI center in
      contrast to most other known FeSI centers has nearly axial symmetry. The EPR
      features of the redox-active centers of P. putida XDH are very similar to those
      of eukaryotic XDHs/xanthine oxidases, suggesting that the environment of each
      center and their functionality are analogous in these enzymes. The midpoint
      potentials determined for the molybdenum, FeSI and FAD redox couples are close to
      each other and resemble those of the corresponding centers in eukaryotic XDHs.

PMID- 11341926
TI  - Effects of mutations of active site residues and amino acids interacting with the
      Omega loop on substrate activation of butyrylcholinesterase.
AB  - The peripheral anionic site (PAS) of human butyrylcholinesterase is involved in
      the mechanism of substrate activation by positively charged substrates and
      ligands. Two substrate binding loci, D70 in the PAS and W82 in the active site,
      are connected by the Omega loop. To determine whether the Omega loop plays a role
      in the signal transduction between the PAS and the active site, residues involved
      in stabilization of the loop, N83, K339 and W430, were mutated. Mutations N83A
      and N83Q caused loss of substrate activation, suggesting that N83 which interacts
      with the D70 backbone may be an element of the transducing system. The K339M and
      W430A mutant enzymes retained substrate activation. Residues W82, E197, and A328
      in the active site gorge have been reported to be involved in substrate
      activation. At butyrylthiocholine concentrations greater then 2 mM, W82A showed
      apparent substrate activation. Mutations E197Q and E197G strongly reduced
      substrate activation, while mutation E197D caused a moderate effect, suggesting
      that the carboxylate of residue E197 is involved in substrate activation.
      Mutations A328F and A328Y showed no substrate activation, whereas A328G retained
      substrate activation. Substrate activation can result from an allosteric effect
      due to binding of the second substrate molecule on the PAS. Mutation W430A was of
      special interest because this residue hydrogen bonds to W82 and Y332. W430A had
      strongly reduced affinity for tetramethylammonium. The bimolecular rate constant
      for reaction with diisopropyl fluorophosphate was reduced 10000-fold, indicating
      severe alteration in the binding area in W430A. The kcat values for
      butyrylthiocholine, o-nitrophenyl butyrate, and succinyldithiocholine were lower.
      This suggested that the mutation had caused misfolding of the active site gorge
      without altering the Omega loop conformation/dynamics. W430 as well as W231 and
      W82 appear to form the wall of the active site gorge. Mutation of any of these
      tryptophans disrupts the architecture of the active site.

PMID- 11341927
TI  - Phosphodiester and phosphorothioate oligonucleotide condensation and preparation
      of antisense nanoparticles.
AB  - Protamine is a cationic peptide with a molecular mass of approx. 4000 Da that is
      able to condense DNA. In the present study it was used to complex antisense
      oligonucleotides (ODNs) and to form solid particles with initial diameters of 90
      150 nm. The reaction was very rapid and occurred by simple mixing of diluted
      solutions of the polycation with the oligonucleotide. The aggregation was
      dependent on the oligonucleotide chain length and the protamine/ODN mass ratio.
      Particle formation required a minimal chain length of nine nucleotides and a mass
      ratio of 0.5:1. The particle surface charge and the number of particles depended
      on the mass ratio. With increasing amounts of the peptide, the number of
      particles and the zeta potential increased. Both negatively and positively
      charged particles improved the stability of oligonucleotides against DNase I
      digestion. Above a mass ratio of 2.5:1 no degradation was found. The uptake of
      unbound rhodamine-labelled ODNs and its complexes with protamine was determined
      with Vero cells under in vitro cell culture conditions at 37 degrees C and 4
      degrees C. At 37 degrees C the cellular uptake increased with increasing mass
      ratio. The internalized oligonucleotides were localized in the cytoplasm and in
      the nucleus of the cells. When Vero cells were treated with these samples at 4
      degrees C for 4 h, no fluorescence could be detected inside the cells. Therefore,
      our data indicate an energy dependent endocytotic uptake mechanism. In contrast,
      spermine and spermidine, which are also known condensation agents, did not
      aggregate with oligonucleotides into nanoparticles under the same conditions.

PMID- 11341928
TI  - Comparison of salt effects on the reactions of acetylcholinesterase with cationic
      and anionic inhibitors.
AB  - The influence of inorganic salts on the inhibition of acetylcholinesterase by
      charged organophosphorous inhibitors has been studied. It has been shown that the
      salt effect on the reaction of acetylcholinesterase with anionic bis(p
      nitrophenyl) phosphate is determined by the influence of added salts on the
      activity coefficient of the inhibitor. In contrast to the salt effects on the
      reaction of acetylcholinesterase with cationic compounds, it does not include
      contribution from the enzyme charges. The smaller salt effect in the case of
      anionic inhibitor can be explained assuming that the anionic inhibitor does not
      form a non-covalent complex with the enzyme before the phosphorylation step of
      the reaction. Comparison of salt effects on the substrate turnover showed that in
      the case of cholinesterases from natural sources they are larger than in the case
      of enzymes expressed in recombinant cell clones. The enhanced salt effects may
      result from post-translational modification of the enzyme.

PMID- 11341929
TI  - Isolation and characterization of a D-7 LEA protein from pollen that stabilizes
      glasses in vitro.
AB  - A heat-soluble protein present in substantial quantities in Typha latifolia
      pollen was purified to homogeneity. The protein was subjected to cyanogen bromide
      cleavage, and the peptides produced were separated by HPLC chromatography and
      sequenced. The two sequences determined were found to be related to the putative
      D76 LEA protein from Brassica napus seeds and one of them to the D-7 LEA protein
      from upland cotton. This suggests the pollen protein to be a member of the LEA
      group III family of proteins. The secondary structure of the protein in solution
      and in the dry state was investigated using Fourier transform IR spectroscopy.
      Whereas the protein in solution was highly unordered, being largely in a random
      coil conformation, the conformation was largely alpha-helical after fast drying.
      Slow drying reversibly led to both alpha-helical and intermolecular extended beta
      sheet structures. When dried in the presence of sucrose, the protein adopted
      alpha-helical conformation, irrespective of drying rate. The effect of the
      protein on the stability of sucrose glasses was also investigated. The dehydrated
      mixture of sucrose and the LEA protein had higher glass transition temperatures
      and average strength of hydrogen bonding than dehydrated sucrose alone. We
      suggest that LEA proteins may play a role together with sugars in the formation
      of a tight hydrogen bonding network in the dehydrating cytoplasm, thus conferring
      long-term stability.

PMID- 11341930
TI  - Effects of ethanol on protein kinase C activity induced by filamentous actin.
AB  - Protein kinase C (PKC) can be activated by interaction with filamentous actin (F
      actin) in the absence of membrane lipids (S.J. Slater, S.K. Milano, B.A.
      Stagliano, K.J. Gergich, J.P. Curry, F.J. Taddeo and C.D. Stubbs, Biochemistry 39
      (2000) 271-280). Here, the effects of ethanol on the F-actin-induced activities
      of a panel of PKC isoforms consisting of 'conventional' (cPKC) alpha, betaI,
      gamma, 'novel' (nPKC) delta, epsilon and 'atypical' (aPKC) zeta were investigated
      using purified PKC and F-actin. Ethanol was found to inhibit the Ca2+- and
      phorbol ester-dependent activities of cPKCalpha and betaI, and the Ca2+- and
      phorbol ester-independent activity of cPKCgamma, whereas the activities of
      nPKCdelta, epsilon and aPKCzeta were unaffected. Although the activities of
      cPKCalpha and betaI induced by saturating levels of phorbol ester were inhibited
      by ethanol, the binding of these isozymes to F-actin was unaffected within the
      same phorbol ester concentration range. Conversely, within submaximal levels of
      phorbol ester, cPKCalpha and betaI activities were unaffected by ethanol whereas
      binding to F-actin was inhibited. The potency of the inhibition of F-actin
      induced cPKCbetaI activity increased with n-alkanol chain length up to n-hexanol,
      after which it declined. The results indicate that PKC activities associated with
      F-actin, and therefore cellular processes involving the actin cytoskeleton, are
      potential targets for ethanol action. The effects of ethanol on these processes
      may differ according to the particular regulating PKC isoform, its intracellular
      localization and the presence of activators and cofactors.

PMID- 11341931
TI  - Structure-based sequence alignment of type-II restriction endonucleases.
AB  - The type-II restriction endonucleases generally do not share appreciable amino
      acid sequence homology. The crystal structures of restriction endonucleases EcoRI
      and BamHI have shown these enzymes to possess striking 3D-structural resemblance,
      i.e., they have a similar overall fold and similar active sites, though they
      possess <23% sequence identity. Structural superimposition of EcoRI, BamHI,
      EcoRV, and PvuII based on active site residues led to sequence alignments which
      showed nine possible sequence motifs. EcoRV and PvuII show a more similar pattern
      than EcoRI and BamHI suggesting that they belong to a different subgroup. The
      motifs are characterized by charged and/or hydrophobic residues. From other
      studies on the structure of these endonucleases, three of the motifs could be
      implicated in DNA binding, three in forming the active site and one in dimer
      formation. However, the motifs were not identifiable by regular sequence
      alignment methods. It is found that motif IX in BamHI is formed by reverse
      sequence order and the motif IX in PvuII is formed from the symmetry related
      monomer of the dimer. The inter-motif distance is also quite different in these
      cases. Of the nine motifs, motif III has been earlier identified as containing
      the PD motif involving one of the active site residues. These motifs were used in
      a modified profile analysis procedure to identify similar regions in eight other
      endonuclease sequences for which structures are not known.

PMID- 11341932
TI  - Cloning, purification and characterisation of Staphylococcus warneri lipase 2.
AB  - A gene encoding an extracellular lipase was identified in Staphylococcus warneri
      863. The deduced lipase is organised as a prepro-protein and has significant
      similarity to other staphylococcal lipases. The mature part of the lipase was
      expressed with an N-terminal histidine tag in Escherichia coli, purified and
      biochemically characterised. The results show that the purified lipase (named
      SWL2) combines the properties of the staphylococcal lipases characterised so far.
      It has both a high preference for short chain substrates and surprisingly, it
      also displays phospholipase activity. Homology alignment was used to analyse
      sequence-function relationships of the staphylococcal lipase family with the aim
      to identify the structural basis underlying the different properties of the
      staphylococcal lipases.

PMID- 11341933
TI  - The Val-210-Ile pathogenic Creutzfeldt-Jakob disease mutation increases both the
      helical and aggregation propensities of a sequence corresponding to helix-3 of
      PrP(C).
AB  - A peptide corresponding to the third helical region within the PrP(C) protein,
      from residues 198 to 218 (helix-3), was synthesised with and without the familial
      210-Val to Ile Creutzfeldt-Jakob disease mutation. The NMR structure of PrP(C)
      predicts no global variation in stability for this mutation, indicating that
      local sequence rather than global structural factors are involved in the
      pathological effects of this mutation. 1H NMR analysis of peptides with and
      without this mutation indicated that it had no significant effect on local
      helical structure. Temperature denaturation studies monitored by CD showed that
      the mutation increased the helical content within this region (helical
      propensity), but did not stabilise the helix toward denaturation (helical
      stability). Aggregation data indicated that, in addition to increasing helical
      propensity, this mutation increased the aggregation propensity of this sequence.
      CD and NMR data indicate that helical interactions, stabilised by the Val-210-Ile
      mutation, may precede the formation of beta-sheet aggregates in this peptide
      sequence. Therefore, this pathological mutation probably does not facilitate
      PrP(C) to PrP(Sc) conversion by directly destabilising the helical structure of
      PrP(C), but may preferentially stabilise PrP(Sc) by facilitating beta-sheet
      formation within this sequence region of PrP. In addition, helical interactions
      between helix-3 in two or more PrP(C) molecules may promote conversion to
      PrP(Sc).

PMID- 11341934
TI  - Towards molecularly imprinted polymers selective to peptides and proteins. The
      epitope approach.
AB  - In this paper, we describe the epitope approach to molecular imprinting. The
      applicability of molecular imprinting, a method that allows the preparation of
      biomimetic compounds (artificial receptors and antibodies), is extended by this
      approach. Our approach makes it possible to obtain imprinted polymers selective
      to peptides and proteins whereas, to date, molecular imprinting has been used
      primarily for the preparation of polymers that selectively bind to relatively low
      molecular weight substances. The epitope approach is based on using (as a
      template) a short peptide that represents only part of a larger peptide or
      protein (as an epitope represents an antigen), which in turn can be recognized by
      the synthesized polymer. It is demonstrated that although other parts of peptides
      can influence the process of molecular recognition, the polymers imprinted with a
      short peptide efficiently recognize both the template and larger peptides (for
      example, oxytocin) that possess the same C-terminal part of the structure.

PMID- 11341935
TI  - Molecular characterization of L-amino acid oxidase from Agkistrodon halys
      blomhoffii with special reference to platelet aggregation.
AB  - L-Amino acid oxidase (LAO, EC 1.4.3.2) is widely distributed in snake venom, and
      induces apoptosis in vascular endothelial cells, causing prolonged bleeding from
      vessel walls at bite sites. The effect of snake venom LAOs on platelet function
      is controversial. Further, we have little information on their structural
      characterization. We purified M (mamushi)-LAO, a single-chain glycoprotein with a
      molecular mass of 60 kDa and a pI of 4.9, from Agkistrodon halys blomhoffii
      (Japanese mamushi) venom, and determined the N-terminal and several internal
      amino acid sequences of this enzyme. Molecular cloning based on these data was
      conducted to elucidate its full-length cDNA structure (2192 nucleotides), which
      includes a putative 18 amino acid residue signal peptide and a 504 residue mature
      subunit. The predicted M-LAO translation product shares 87.3% identity with that
      of Crotalus adamanteus (Southeastern diamondback rattlesnake) LAO. M-LAO, up to a
      final concentration of 2.6 microM, inhibited both agonist- and shear stress
      induced platelet aggregation (SIPA) dose-dependently. In agonist-induced platelet
      aggregation, M-LAO predominantly inhibited the second aggregation, but with a
      marginal inhibition of the first. In SIPA, the inhibition was more dramatic under
      low-shear stress than high-shear stress, and was enhanced by the presence of L
      leucine, a substrate of this enzyme. Catalase, a H2O2 scavenger, totally quenched
      such enhancement. These results suggest that M-LAO inhibits the interaction
      between activated platelet integrin alphaIIb/beta3 and fibrinogen through the
      continuous generation of H2O2, and may contribute to prolonged bleeding from the
      vessels at snake bite sites.

PMID- 11341936
TI  - Detection of regions in the MC1 receptor of importance for the selectivity of the
      MC1 receptor super-selective MS04/MS05 peptides.
AB  - We have investigated the ability of our earlier identified MS04-MS05 MSH-peptide
      analogues to bind to chimeric MC1-MC3 receptors. While the MS04 and MS05 peptides
      bind with nanomolar and sub-nanomolar affinities to the wild type MC1 receptor,
      they bind only with micromolar affinities for the wild type MC3 receptor, thus
      being the hitherto most MC1 receptor selective ligands. Upon exchanging portions
      involving transmembrane regions TM1, TM2-3, and TM6-7 of the MC1 receptor with
      corresponding portions of the MC3 receptor both of these peptides showed major
      losses of affinities. By contrast exchanges involving TM4-5 did not appreciably
      affect the affinity of either MS04 or MS05. Our data suggest that the binding
      pocket for the MS04-MS05 MSH-peptides is located between TM1-3 and TM6-7 of the
      melanocortin receptors.

PMID- 11341937
TI  - High-affinity binding of NADPH to camel lens zeta-crystallin.
AB  - Fluorescence spectrum of camel lens zeta-crystallin, a major protein in the lens
      of camelids and histicomorph rodents, showed maximum emission at 315 nm. This
      emission maximum is blue shifted compared to most proteins, including alpha
      crystallin, and appeared to be due to tryptophan in highly hydrophobic
      environment. Interaction of NADPH with zeta-crystallin quenched the protein
      fluorescence and enhanced the fluorescence of bound NADPH. Analysis of
      fluorescence quenching suggested high-affinity interaction between NADPH and zeta
      crystallin with an apparent Km<0.45 microM. This value is at least an order of
      magnitude lower than that suggested by activity measurements. Analysis of NADPH
      fluorescence showed a biphasic curve representing fluorescence of free- and bound
      NADPH. The intersection between free- and bound-NADPH closely paralleled the
      enzyme concentration, suggesting one mole of NADPH was bound per subunit of the
      enzyme. Phenanthrenequinone (PQ), the substrate of zeta-crystallin, also was able
      to quench the fluorescence of zeta-crystallin, albeit weaker than NADPH.
      Quantitative analysis suggested that zeta-crystallin had low affinity for PQ in
      the absence of NADPH, and PQ binding induced significant conformational changes
      in zeta-crystallin.

PMID- 11341938
TI  - Effect of captopril on mushroom tyrosinase activity in vitro.
AB  - The study presented here demonstrates that the antihypertensive drug captopril
      ([2S]-N-[3-mercapto-2-methylpropionyl]-L-proline) is an irreversible non
      competitive inhibitor and an irreversible competitive inhibitor of the
      monophenolase and diphenolase activities of mushroom tyrosinase when L-tyrosine
      and L-DOPA were assayed spectrophotometrically in vitro, respectively. Captopril
      was rendered unstable by tyrosinase catalysis because of the interaction between
      the enzymatic-generated product (o-quinone) and captopril to give rise to a
      colourless conjugate. Therefore, captopril was able to prevent melanin formation.
      The spectrophotometric recordings of the inhibition of tyrosinase by captopril
      were characterised by the presence of a lag period prior to the attainment of an
      inhibited steady state rate. The lag period corresponded to the time in which
      captopril was reacting with the enzymatically generated o-quinone. Increasing
      captopril concentrations provoked longer lag periods as well as a concomitant
      decrease in the tyrosinase activity. Both lag period and steady state rate were
      dependent of captopril, substrate and tyrosinase concentrations. The inhibition
      of both monophenolase and diphenolase activities of tyrosinase by captopril
      showed positive kinetic co-operativity which arose from the protection of both
      substrate and o-quinone against inhibition by captopril. Inhibition experiments
      carried out using a latent mushroom tyrosinase demonstrated that captopril only
      bound the enzyme at its active site. The presence of copper ions only partially
      prevented but not reverted mushroom tyrosinase inhibition. This could be due to
      the formation of both copper-captopril complex and disulphide interchange
      reactions between captopril and cysteine rich domains at the active site of the
      enzyme.

PMID- 11341939
TI  - A study of protein-carotenoid interactions in the astaxanthin-protein
      crustacyanin by absorption and Stark spectroscopy; evidence for the presence of
      three spectrally distinct species.
AB  - Molecular mechanisms underlying the peculiar spectral properties of the
      carotenoid astaxanthin in alpha-crustacyanin, the blue carotenoprotein isolated
      from the exoskeleton of the lobster Homarus gammarus, were investigated by
      comparing the basic electrooptical parameters of astaxanthin free in vitro with
      those of astaxanthin in the complex. Absorption and electroabsorption (Stark
      effect) spectra were obtained for alpha-crustacyanin in low-temperature glasses
      to provide information about the molecular interactions that lead to the large
      bathochromic shift of the spectra resulting from this complexation. The low
      temperature spectra reveal the presence of at least three spectral forms of alpha
      crustacyanin, with vibronic (0-0) transitions at 14000 cm(-1), 13500 cm(-1) and
      11600 cm(-1) (corresponding to approximately 630, 660 and 780 nm, respectively,
      at room temperature) and with relative aboundance 85%, 10% and 5%. The longer
      wavelength absorbing species have not previously been detected. The changes in
      polarizability and in permanent dipole moments associated with the S0-->S2
      electronic transition for all these forms are about 1.5 times larger than for
      isolated astaxanthin. The results are discussed with reference to the symmetric
      polarization model for astaxanthin in alpha-crustacyanin.

PMID- 11341940
TI  - Interaction between alphaB-crystallin and the human 20S proteasomal subunit
      C8/alpha7.
AB  - alphaB-Crystallin, a member of the small heat shock protein (sHsp) family, can
      bind unfolding proteins, but is unable to refold them. To fulfil its protective
      function in vivo it is therefore likely to interact with other cellular proteins.
      Here we report that alphaB-crystallin binds very specifically both in vitro and
      in vivo to C8/alpha7, one of the 14 subunits of the 20S proteasome. The C8/alpha7
      protein forms heterogeneous complexes with alphaB-crystallin of about 540 kDa.
      However, no strong interaction between alphaB-crystallin and 20S proteasomes was
      observed. Since both proteins are localized in the cytoplasm, the interaction
      between alphaB-crystallin and C8/alpha7 subunit might affect the assembly of the
      proteasome complex or facilitate the degradation of unfolded proteins bound to
      alphaB-crystallin.

PMID- 11341941
TI  - Identification of equilibrium and kinetic intermediates involved in folding of
      urea-denatured creatine kinase.
AB  - The unfolding transition and kinetic refolding of dimeric creatine kinase after
      urea denaturation were monitored by intrinsic fluorescence and far ultraviolet
      circular dichroism. An equilibrium intermediate and a kinetic folding
      intermediate were identified and characterized. The fluorescence intensity of the
      equilibrium intermediate is close to that of the unfolded state, whereas its
      ellipticity at 222 nm is about 50% of the native state. The transition curves
      measured by these two methods are therefore non-coincident. The kinetic folding
      intermediate, formed during the burst phase of refolding under native-like
      conditions, possesses 75% of the native secondary structure, but is mostly
      lacking in native tertiary structure. In moderate concentrations of urea, only
      the initial, rapid change in fluorescence intensity or negative ellipticity is
      observed, and the final state values do not reach the equivalent unfolding
      values. The unfolding and refolding transition curves measured under identical
      conditions are non-coincident within the transition from intermediate to fully
      unfolded state. It is observed by SDS-PAGE that disulfide bond-linked dimeric or
      oligomeric intermediates are formed in moderate urea concentrations, especially
      in the refolding reaction. These rapidly formed, soluble intermediates represent
      an off-pathway event that leads to the hysteresis in the refolding transition
      curves.

PMID- 11341942
TI  - Comparison of photovoltaic behaviors for horseradish peroxidase and its mimicry
      by surface photovoltage spectroscopy.
AB  - Surface photovoltage spectroscopy (SPS) was chosen to study the photovoltaic
      behavior of horseradish peroxidase (HRP), hemin and immobilized hemin
      (poly(NIPAAm/MBA/hemin)). Different photovoltaic behaviors were observed in these
      three systems. In air, similar SPS curves were found for HRP and
      poly(NIPAAm/MBA/hemin) with different response intensities. However,
      poly(NIPAAm/MBA/hemin) showed a wider changing range upon increasing the positive
      and negative bias to 1.0 V. The SPS of hemin showed a total different behavior
      when an external positive potential was applied. In vacuum, clearly different
      photovoltaic behaviors were found. Moreover, the response value decreased when
      HRP was exposed to O2, the SPS intensity was different from that in air, and
      could be altered by changing the external biases. On the other hand, the SPS
      could not be changed before and after poly(NIPAAm/MBA/hemin) was exposed to O2.
      These differences may result from different chemical microenvironments for hemin
      in HRP versus that in poly(NIPAAm/MBA/hemin). It could be concluded that H2O and
      O2 were important factors affecting the photovoltage response in HRP, but only
      H2O played this important role in poly(NIPAAm/MBA/hemin).

PMID- 11341943
TI  - Comparison of sucrase-free isomaltase with sucrase-isomaltase purified from the
      house musk shrew Suncus murinus.
AB  - We purified sucrase-isomaltase and sucrase-free isomaltase from a normal and a
      sucrase-deficient line, respectively, of the house musk shrew Suncus murinus and
      examined the effects of mutation on enzyme structure and activities. Recent cDNA
      cloning studies have predicted that sucrase-free mutant isomaltase lacks the C
      terminal 69 amino acids of normal isomaltase, as well as the entire sucrase. On
      SDS-polyacrylamide gel electrophoresis purified sucrase-free isomaltase gave a
      single protein band of 103 kDa, while sucrase-isomaltase gave two major protein
      bands of 106 and 115 kDa. The 115, but not 106, kDa band was quite similar to the
      103 kDa band on Western blotting with Aleuria aurantia lectin and antibody
      against shrew sucrase-isomaltase, suggesting that the 115 and 103 kDa bands are
      due to normal and mutant isomaltases, respectively, in accordance with the above
      prediction. Purified isomaltase and sucrase-isomaltase were similar in Km and
      Vmax (based on isomaltase mass) values for isomaltose hydrolysis and in
      inhibition of isomaltase activity by antibody against rabbit sucrase-isomaltase,
      suggesting that the enzymatic properties of isomaltase are mostly unaffected by
      mutation.

PMID- 11341944
TI  - PLS modeling of chimeric MS04/MSH-peptide and MC1/MC3-receptor interactions
      reveals a novel method for the analysis of ligand-receptor interactions.
AB  - A novel method has been developed for the analysis of ligand-receptor
      interactions. The method utilizes binding data generated from the analysis of
      chimeric proteins with chimeric peptides. To each chimeric part of the peptide
      and receptor are assigned descriptors, thus creating a matrix of X descriptors.
      These descriptors are then correlated with the experimentally determined
      interaction binding affinities for each chimeric receptor/peptide pair by use of
      partial least-squares projection to latent structures (PLS). The method was
      applied to analyze the interactions of chimeric MSH-peptides with wild-type MC1
      and MC3 receptors, and MC1/MC3 receptor chimeras (in total 40 peptide-receptor
      combinations). Two types of PLS models could be created, one that revealed the
      relationships between receptor and peptide structure and peptide binding pK(i)
      values (i.e., affinity) (R2 and Q2 being 0.71 and 0.62, respectively), and
      another that revealed the relationships between peptide and receptor structure
      and peptide-receptor selectivity (R2 and Q2 being 0.64 and 0.57, respectively).
      After addition of cross-terms these models improved significantly; the R2 and Q2
      being 0.93 and 0.75 for affinity, and 0.92 and 0.72 for selectivity,
      respectively. The analysis shows that the high affinity of the MSH-peptides is
      primarily achieved by interactions of the peptides' C-terminal amino acids with
      TM2 and TM3 of the receptor, and, to a lesser extent, by the interaction of the N
      terminus with TM1, TM2 and TM3 of the receptor. However, in contrast, the MC1
      receptor selectivity is primarily determined by an interaction of the peptides' N
      termini with TM2/3 of the receptor. Moreover, the cross-terms of the PLS model
      revealed the existence of a strong interaction between TM6/7 and TM2/3 of the
      receptors.

PMID- 11341945
TI  - Differential induction of peroxisomal populations in subcellular fractions of rat
      liver.
AB  - In rat liver, peroxisome proliferators induce profound changes in the number and
      protein composition of peroxisomes, which upon subcellular fractionation is
      reflected in heterogeneity in sedimentation properties of peroxisome populations.
      In this study we have investigated the time course of induction of the
      peroxisomal proteins catalase, acyl-CoA oxidase (ACO) and the 70 kDa peroxisomal
      membrane protein (PMP70) in different subcellular fractions. Rats were fed a di(2
      ethylhexyl)phthalate (DEHP) containing diet for 8 days and livers were removed at
      different time-points, fractionated by differential centrifugation into nuclear,
      heavy and light mitochondrial, microsomal and soluble fractions, and organelle
      marker enzymes were measured. Catalase was enriched mainly in the light
      mitochondrial and soluble fractions, while ACO was enriched in the nuclear
      fraction (about 30%) and in the soluble fraction. PMP70 was found in all
      fractions except the soluble fraction. DEHP treatment induced ACO, catalase and
      PMP70 activity and immunoreactive protein, but the time course and extent of
      induction was markedly different in the various subcellular fractions. All three
      proteins were induced more rapidly in the nuclear fraction than in the light
      mitochondrial or microsomal fractions, with catalase and PMP70 being maximally
      induced in the nuclear fraction already at 2 days of treatment. Refeeding a
      normal diet quickly normalized most parameters. These results suggest that
      induction of a heavy peroxisomal compartment is an early event and that induction
      of 'small peroxisomes', containing PMP70 and ACO, is a late event. These data are
      compatible with a model where peroxisomes initially proliferate by growth of a
      heavy, possibly reticular-like, structure rather than formation of peroxisomes by
      division of pre-existing organelles into small peroxisomes that subsequently
      grow. The various peroxisome populations that can be separated by subcellular
      fractionation may represent peroxisomes at different stages of biogenesis.

PMID- 11341946
TI  - Effects of hyperoxia and iron on iron regulatory protein-1 activity and the
      ferritin synthesis in mouse peritoneal macrophages.
AB  - Ferritin is an intracellular iron storage protein and its translation is
      inhibited by binding of iron regulatory proteins (IRPs) to the iron-responsive
      element (IRE) located in the 5' untranslated region of its mRNA. In this paper,
      we have investigated the effect of hyperoxia and iron on the binding activity of
      IRP-1 and the ferritin synthesis in mouse peritoneal macrophages. The binding
      activity of IRP-1 was increased and the ferritin synthesis was suppressed when
      the macrophages were cultured under hyperoxia, and the reverse occurred under
      hypoxia. Iron diminished the IRP-1-binding activity and the enhanced synthesis of
      ferritin. However, this effect was arrested under hyperoxia. Consistently,
      hypoxia-induced loss of binding activity of IRP-1 and the enhanced synthesis of
      ferritin were blocked in the presence of an iron chelator deferoxamine. These
      alterations of the binding activity of IRP-1 in response to oxygen and iron were
      not reproduced in the cell-free extract. The data suggest that in the macrophages
      oxygen and iron inversely act on the binding activity of IRP-1 and the ferritin
      synthesis, and that intracellular mechanism(s) to sense iron and/or oxygen is
      required for these actions.

PMID- 11341947
TI  - Ribosomes with large synthetic N-terminal extensions of protein S15 are active in
      vivo.
AB  - The genes for ribosomal proteins S4, S13 or S15 were fused with the gene for
      staphylococcal protein A, or derivatives thereof (2A'-7A'). The gene fusions were
      introduced into Escherichia coli strains, mutated in the corresponding ribosomal
      protein gene, by transformation. These mutated ribosomal proteins cause a
      phenotype that can be complemented. Thus, the phenotype of the transformants was
      tested and the ribosomal proteins were analyzed. The S4 N-terminal fusion protein
      severely disturbed growth of both the mutant and the wild-type strains. The S13 C
      terminal fusion protein was proteolyzed close to the fusion point, giving a
      ribosomal protein moiety that could assemble into the ribosome normally. S15 N
      terminal fusion proteins complemented a cold-sensitive strain lacking protein S15
      in its ribosomes. These fused proteins were assembled into active ribosomes. The
      position of S15 in the 30S ribosomal subunit is well known. Therefore, in
      structural studies of the ribosome in vivo, the S15 fusion proteins can be used
      as a physical reporter for S15.

PMID- 11341948
TI  - Binding properties of human albumin modified by covalent binding of penicillin.
AB  - Derivatisation of lysine residues in human albumin was performed in vitro by
      reaction with penicillin G. This modification reaction has been reported to occur
      in patients treated with high dosages of the antibiotic. The structure of the
      modified protein was characterised by mass spectrometry and circular dichroism.
      The number of the lysine residues involved depends on the time of incubation and
      on the drug/protein molar ratio. The secondary structure of the modified protein
      does not change significantly with respect to the native protein. Furthermore,
      the binding properties of the modified albumin were characterised by CD
      spectroscopy. Phenylbutazone, diazepam and bilirubin, known to bind to specific
      binding areas, were used as markers. A decrease of the affinity to the high
      affinity binding sites was observed after the modification.

PMID- 11341949
TI  - Mutual effects of alpha-actinin, calponin and filamin on actin binding.
AB  - The mutual effect of three actin-binding proteins (alpha-actinin, calponin and
      filamin) on the binding to actin was analyzed by means of differential
      centrifugation and electron microscopy. In the absence of actin alpha-actinin,
      calponin and filamin do not interact with each other. Calponin and filamin do not
      interfere with each other in the binding to actin bundles. Slight interference
      was observed in the binding of alpha-actinin and calponin to actin bundles.
      Higher ability of calponin to depress alpha-actinin binding can be due to the
      higher stoichiometry calponin/actin in the complexes formed. The largest
      interference was observed in the pair filamin-alpha-actinin. These proteins
      interfere with each other in the binding to the bundled actin filaments; however,
      neither of them completely displaced another protein from its complexes with
      actin. The structure of actin bundles formed in the presence of any one actin
      binding protein was different from that observed in the presence of binary
      mixtures of two actin-binding proteins. In the case of calponin or its binary
      mixtures with alpha-actinin or filamin the total stoichiometry actin-binding
      protein/actin was larger than 0.5. This means that alpha-actinin, calponin and
      filamin may coexist on actin filaments and more than mol of any actin-binding
      protein is bound per two actin monomers. This may be important for formation of
      different elements of cytoskeleton.

PMID- 11341954
TI  - Nuclear phospholipase C and signaling.

PMID- 11341955
TI  - Abundant expression of uncoupling protein-2 in the small intestine: up-regulation
      by dietary fish oil and fibrates.
AB  - Mitochondrial uncoupling protein-2 (UCP-2) is widely expressed in various
      mammalian tissues, although its physiological functions are not well understood.
      We examined the effects of dietary fish oil on UCP-2 expression in the rat small
      intestine, in which UCP-2 mRNA levels are higher than in other organs. Feeding
      with fish oil (20%) up-regulated UCP-2 mRNA within 6 days in the small intestine
      as well as the liver, compared to feeding with soybean oil. This was mimicked by
      feeding with agonists for peroxisome proliferator-activated receptor alpha
      (PPARalpha) such as fenofibrate and bezafibrate, but not the PPARgamma agonist
      troglitazone. The bezafibrate-induced increase in UCP-2 expression was found
      within 2 days in the small intestine, but only after 6 days in the liver. The up
      regulation of UCP-2 was also found in cultured intestinal epithelial cells (IEC
      6) treated for 24 h with various long-chain fatty acids and PPARalpha agonists.
      These results indicated that intestinal UCP-2 is up-regulated through direct
      activation of PPARalpha by dietary fatty acids.

PMID- 11341956
TI  - Identification of novel membrane-bound phospholipase D from Streptoverticillium
      cinnamoneum, possessing only hydrolytic activity.
AB  - A membrane-bound phospholipase D (PLD) has been identified and isolated in a
      soluble form from an actinomycete, Streptoverticillium cinnamoneum. The enzyme
      has a monomeric structure with a molecular size of about 37 kDa, being the
      smallest among the enzymes so far reported. The enzyme catalyzes the hydrolysis
      of phosphatidylethanolamine and phosphatidylserine as preferred substrates, but
      not the transphosphatidylation reaction of their phospholipid groups to ethanol.
      Together with the absence of immunochemical cross-reactivity, these enzymatic
      properties demonstrate that the membrane-bound enzyme is distinct from the
      extracellular enzyme recently characterized and cloned from the same bacterial
      strain [C. Ogino et al., J. Biochem. 125 (1999) 263-269] and is therefore
      regarded as a novel prokaryotic PLD.

PMID- 11341957
TI  - The Rossmann fold of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a
      nuclear docking site for antisense oligonucleotides containing a TAAAT motif.
AB  - The subcellular localisation of oligodeoxynucleotides (ODN) is a major limitation
      for their use against nuclear targets. In this study we demonstrate that an
      antisense ODN directed against cytosolic phospholipase A(2) (cPLA2) mRNA is
      efficiently taken up and accumulates in the nuclei of endothelial cells (HUVEC),
      human monocytes and HeLa cells. Gel shift experiments and incubation of cells
      with oligonucleotide derivatives show that the anti-cPLA2 oligo binds a 37 kDa
      protein in nuclear extracts. The TAAAT sequence was identified as the major
      binding motif for the nuclear protein in competition experiments with mutated
      ODNs. Modification of the AAA triplet resulted in an ODN which failed to localise
      in the nucleus. Moreover, inserting a TAAAT motif into an ODN localising in the
      cytosol did not modify its localisation. The 37 kDa protein was purified and
      identified after peptide sequencing as glyceraldehyde-3-phosphate dehydrogenase
      (GAPDH). It was shown by confocal microscopy that GAPDH co-localises with anti
      cPLA2 ODN in the nucleus and commercial GAPDH effectively binds the oligo.
      Competition experiments with increasing concentration of NAD(+) co-factor
      indicate that the GAPDH Rossmann fold is a docking site for antisense
      oligonucleotides containing a TAAAT motif.

PMID- 11341958
TI  - 1H NMR-visible mobile lipid domains correlate with cytoplasmic lipid bodies in
      apoptotic T-lymphoblastoid cells.
AB  - The presence of nuclear magnetic resonance (NMR)-visible mobile lipid (ML)
      domains in apoptotic lymphoblasts suggests alterations in neutral lipid
      metabolism and compartmentation during programmed cell death. The detection of
      similar ML signals in activated lymphocytes raises questions about common
      mechanisms of ML formation during apoptosis and upon lymphoblast stimulation.
      Structure and subcellular localization of ML domains were therefore investigated
      by NMR, fluorescence and electron microscopy in Jurkat T-lymphoblasts either
      induced to apoptosis (by anthracyclines or dexamethasone or by serum deprivation)
      or activated by phorbol myristate acetate (PMA) plus ionomycin. ML contents in
      drug-treated cells correlated linearly with apoptosis, irrespective of the
      specific inducer and cell cycle arrest phase (r = 0.993, P < 0.001). Similar ML
      levels were measured in drug-induced apoptotic cells (A approximately 30-40%) and
      in non-apoptotic PMA/ionomycin-treated lymphoblasts (72 h). Lower ML contents
      were instead formed in serum-deprived apoptotic cells, with respect to controls.
      Increases in ML signals were associated, in either apoptotic or activated cells,
      with the accumulation of cytoplasmic, osmophilic lipid bodies (diameter < or =
      1.0 microm), surrounded by own membrane, possessing intramembrane particles. The
      results support the hypothesis that ML are formed in the cytoplasm of drug
      induced apoptotic cells during an early, 'biochemically active' phase of
      programmed cell death.

PMID- 11341959
TI  - Group X secretory phospholipase A(2) induces potent productions of various lipid
      mediators in mouse peritoneal macrophages.
AB  - We have previously shown the expression of group X secretory phospholipase A(2)
      (sPLA(2)-X) in mouse splenic macrophages and its powerful potency for releasing
      fatty acids from various intact cell membranes. Here, we examined the potency of
      sPLA(2)-X in the production of lipid mediators in murine peritoneal macrophages.
      Mouse sPLA(2)-X was found to induce a marked release of fatty acids including
      arachidonic acid and linoleic acid, which contrasted with little, if any, release
      by the action of group IB and IIA sPLA(2)s. In resting macrophages, sPLA(2)-X
      elicited a modest production of prostaglandin E(2) and thromboxane A(2). After
      the induction of cyclooxygenase-2 (COX-2) by pretreatment with
      lipopolysaccharide, a dramatic increase in the production of these eicosanoids
      was observed in sPLA(2)-X-treated macrophages, which was completely blocked by
      the addition of either the specific sPLA(2) inhibitor indoxam or the COX
      inhibitor indomethacin. In accordance with its higher hydrolyzing activity toward
      phosphatidylcholine, mouse sPLA(2)-X induced a potent production of
      lysophosphatidylcholine. These findings strongly suggest that sPLA(2)-X plays a
      critical role in the production of various lipid mediators from macrophages.
      These events might be relevant to the progression of various pathological states,
      including chronic inflammation and atherosclerosis.

PMID- 11341960
TI  - Active-site residues of a plant membrane-bound fatty acid elongase beta-ketoacyl
      CoA synthase, FAE1 KCS.
AB  - The fatty acid elongase-1 beta-ketoacyl-CoA synthase, FAE1 KCS, a seed-specific
      elongase condensing enzyme from Arabidopsis, is involved in the production of
      eicosenoic (C20:1) and erucic (C22:1) acids. Alignment of the amino acid
      sequences of FAE1 KCS, KCS1, and five other putative elongase condensing enzymes
      (KCSs) revealed the presence of six conserved cysteine and four conserved
      histidine residues. Each of the conserved cysteine and histidine residues was
      individually converted by site-directed mutagenesis to both alanine and serine,
      and alanine and lysine respectively. After expression in yeast cells, the mutant
      enzymes were analyzed for their fatty acid elongase activity. Our results
      indicated that only cysteine 223 is an essential residue for enzyme activity,
      presumably for acyl chain transfer. All histidine substitutions resulted in
      complete loss of elongase activity. The loss of activity of these mutants was not
      due to their lower expression level since immunoblot analysis confirmed each was
      expressed to the same extent as the wild type FAE1 KCS.

PMID- 11341961
TI  - Group IIA and group V secretory phospholipase A(2): quantitative analysis of
      expression and secretion and determination of the localization and routing in rat
      mesangial cells.
AB  - Mesangial cells can be induced to express group IIA and group V secretory
      phospholipase A(2) (sPLA(2)) at the mRNA level and at the protein level. In this
      report we quantitatively analyze the expression of both proteins in stimulated
      cells by Western blot techniques. We found that 75-80% of the total amount of
      synthesized group IIA sPLA(2) was secreted. The synthesized group V sPLA(2),
      however, was present almost exclusively intracellularly. The amount of group V
      present in the cell was comparable to the intracellular amount of group IIA
      sPLA(2). We furthermore studied the localization and routing of both proteins.
      Using fusion proteins of the group IIA or group V pre-sPLA(2) with green
      fluorescent protein it was established that both presequences are able to direct
      the proteins to the Golgi system. In immunofluorescence studies group V sPLA(2)
      expressed by rat mesangial cells was located in a punctate pattern in the cytosol
      with an enrichment near the nucleus. Immunofluorescent confocal laser scanning
      microscopy revealed that the group V and IIA sPLA(2) show partial colocalization
      in a Golgi-like structure in the inner part in the cell, but no colocalization
      was seen in the vesicles in the cytoplasm. The images also showed that group IIA
      sPLA(2) was located throughout the cell while group V was mainly present in the
      inner part of the cell. After treatment of the cells with brefeldin A or monensin
      the group IIA enzyme could no longer be detected, while group V sPLA(2) was still
      present although its localization was somewhat dependent on the treatment.
      Collectively, these results indicate that the two enzymes differ in both
      localization and routing in the cell, which underscores the hypothesis that the
      enzymes might have different functions.

PMID- 11341962
TI  - Presence of a phospholipase D (PLD) distinct from PLD1 or PLD2 in human
      neutrophils: immunobiochemical characterization and initial purification.
AB  - Utilizing the transphosphatidylation reaction catalyzed by phospholipase D (PLD)
      in the presence of a primary alcohol and the short-chain phospholipid PC8, we
      have characterized the enzyme from human neutrophils. A pH optimum of 7.8-8.0 was
      determined. PIP(2), EDTA/EGTA, and ATP were found to enhance basal PLD activity
      in vitro. Inhibitory elements were: oleate, Triton X-100, n-octyl-beta
      glucopyranoside, divalent cations, GTPgammaS and H(2)O(2). The apparent K(m) for
      the butanol substrate was 0.1 mM and the V(max) was 6.0 nmol mg(-1) h(-1).
      Immunochemical analysis by anti-pan PLD antibodies revealed a neutrophil PLD of
      approximately 90 kDa and other bands recognized minimally by anti-PLD1 or anti
      PLD2 antibodies. The 90-kDa protein is tyrosine-phosphorylated upon cell
      stimulation with GM-CSF and formyl-Met-Leu-Phe. Protein partial purification
      using column liquid chromatography was performed after cell subfractionation.
      Based on the enzyme's regulatory and inhibitory factors, and its molecular
      weight, these data indicate an enzyme isoform that might be different from the
      mammalian PLD1/2 forms described earlier. The present results lay the foundation
      for further purification of this granulocyte PLD isoform.

PMID- 11341963
TI  - Effects of high-density lipoprotein(2) on cholesterol transport and acyl-coenzyme
      A:cholesterol acyltransferase activity in P388D1 macrophages.
AB  - High-density lipoproteins are the putative vehicles for cholesterol removal from
      monocyte-derived macrophages, which are an important cell type in all stages of
      atherosclerosis. The role of HDL(2), an HDL subclass that accounts for most
      variation in plasma HDL-cholesterol concentration, in cholesterol metabolism in
      monocyte-derived macrophages is not known. In this study, the dose-dependent
      effects of HDL(2) on cellular cholesterol mass, efflux, and esterification, and
      on cellular cholesteryl ester (CE) hydrolysis using the mouse macrophage P388D1
      cell line was investigated. HDL(2) at low concentrations (40 microg protein/ml)
      decreased CE content without affecting cellular free cholesterol content (FC), CE
      hydrolysis, or cholesterol biosynthesis. In addition, HDL(2) at low
      concentrations reduced cellular acyl-coenzyme A:cholesterol acyltransferase
      (ACAT) activity and increased FC efflux from macrophages. Thus, HDL(2) has two
      potential roles in reverse cholesterol transport. In one, HDL(2) is an acceptor
      of macrophage FC. In the other, more novel role, HDL(2) increases the
      availability of macrophage FC through the inhibition of ACAT. Elucidation of the
      mechanism by which HDL(2) inhibits ACAT could identify new therapeutic targets
      that enhance the transfer of cholesterol from macrophages to the liver.

PMID- 11341964
TI  - Free leucine dissociates homo- and heterodimers formed between proteins
      containing leucine heptad repeats.
AB  - A highly specific method for the dissociation of protein dimers has been
      developed. The method involves exposure of the dimers to free leucine at a
      concentration ranging between 3 and 10 mM. Using this method it has been possible
      to dissociate goat uterine oestrogen receptor homodimers, heterodimers formed
      between the non-activated oestrogen receptor (naER) and the oestrogen receptor
      activation factor (E-RAF) of the goat uterus, c-jun homodimers derived from
      bovine bone marrow and also glucocorticoid receptor homodimers isolated from rat
      liver cytosol. The pattern of dimer dissociation by leucine clearly
      differentiates two classes of proteins. The first is represented by steroid
      hormone receptors where dimerization is apparently contributed by both coiled
      coil dimerization interfaces and the conserved heptad repeats of leucine. The
      second is represented by oncoproteins like c-fos and c-jun which dimerize through
      the exclusive involvement of leucine zippers. The patterns of dissociation of
      these two groups of proteins from the concerned affinity columns are distinctly
      different. This indicates a possibility that the elution pattern may be used as a
      yardstick to determine whether two proteins dimerize through the exclusive
      involvement of leucine zippers or whether coiled-coil interfaces are also
      involved in the dimerization process.

PMID- 11341965
TI  - Establishment of variant PC12 subclones deficient in stimulation-secretion
      coupling.
AB  - Clonal rat pheochromocytoma (PC12) cells have been widely used to study the
      molecular mechanism of exocytosis. We have isolated variant PC12 subclones with
      deficiencies in stimulation-secretion coupling, by a single cell recloning, and
      investigated the defects. PC12-1G2 hardly released dopamine following high-K(+)
      induced depolarization, but normal release was evoked by the Ca(2+)-ionophore,
      ionomycin. Fura-2 fluorometry indicated that a nicardipine-sensitive component of
      Ca(2+) influx was missing, suggesting that PC12-1G2 has defects in L-type Ca(2+)
      channel function. PC12-2B3 was not responsive to high-K(+)-induced depolarization
      and ionomycin, and voltage-dependent Ca(2+) entry was identical to that of the
      normal clone. Electron microscopy revealed that the number of vesicles adjacent
      or directly attached to the plasma membrane was decreased in PC12-2B3. The
      expression of presynaptic proteins was analyzed by immunoblotting using a panel
      of antibodies. Syntaxin 1, VAMP-2, SNAP-25, Munc18, Rab3C and Sec-6 were
      decreased compared to the control clone and that of synaptophysin was extremely
      low. PC12-D60 synthesized and released dopamine normally, but had almost lost its
      catecholamine-uptake activity. These results show that multiple PC12 cells
      variants are spontaneously generated, and that recloning can select PC12
      subclones useful for the study of the molecular mechanisms of neurotransmitter
      release.

PMID- 11341966
TI  - Cloning and characterization of an inhibitor of apoptosis protein (IAP) from
      Bombyx mori.
AB  - We cloned a novel inhibitor of apoptosis protein (IAP) family member, BmIAP, from
      Bombyx mori BmN cells. BmIAP contains two baculoviral IAP repeat (BIR) domains
      followed by a RING domain. BmIAP shares striking amino acid sequence similarity
      with lepidopteran IAPs, SfIAP and TnIAP, and with two baculoviral IAPs, CpIAP and
      OpIAP, suggesting evolutionary conservation. BmIAP blocks programmed cell death
      (apoptosis) in Spodoptera frugiperda Sf-21 cells induced by p35 deficient
      Autographa californica nucleopolyhedrovirus (AcMNPV). This anti-apoptotic
      function requires both the BIR domains and RING domain of BmIAP. In mammalian
      cells, BmIAP inhibits Bax induced but not Fas induced apoptosis. Further
      biochemical data suggest that BmIAP is a specific inhibitor of mammalian caspase
      9, an initiator caspase in the mitochondria/cytochrome-c pathway, but not the
      downstream effector proteases, caspase-3 and caspase-7. These results suggest
      that suppression of apoptosis by lepidopteran IAPs in insect cells may involve
      inhibition of an upstream initiator caspase in the conserved
      mitochondria/cytochrome-c pathway for apoptosis.

PMID- 11341967
TI  - The role of calcium in the activation of glycogen phosphorylase in the fat body
      of the fruit beetle, Pachnoda sinuata, by hypertrehalosaemic hormone.
AB  - The role of calcium in the mediation of the hypertrehalosaemic signal of the
      endogenous neuropeptide Mem-CC was investigated in vitro and in vivo in the
      cetoniid beetle Pachnoda sinuata. The presence of Mem-CC increases the influx of
      extracellular 45Ca(2+) into the fat body as well as the efflux of 45Ca(2+) from
      pre-loaded fat body into the incubation medium. Extracellular calcium is
      essential to exert maximal activation of the fat body glycogen phosphorylase by
      saturating doses of Mem-CC (0.3 nM). This effect of extracellular Ca(2+) is dose
      dependent: maximal activation of glycogen phosphorylase by Mem-CC is achieved at
      calcium concentrations of approximately 1.2 mM and the ED(50) was calculated to
      be 0.6 mM. Both, thimerosal and thapsigargin caused a stimulation of carbohydrate
      metabolism in the fat body, suggesting that a release of calcium from the
      endoplasmic reticulum is involved in this process. However, neither entry of
      extracellular calcium nor the release from the endoplasmic reticulum are
      sufficient alone for a full activation of the phosphorylase. The results of the
      present study suggest that calcium from extracellular as well as from
      intracellular sources is part of the second messenger system for the transduction
      of the hypertrehalosaemic signal of Mem-CC in the fat body of P. sinuata.

PMID- 11341968
TI  - Regulation of phospholipase D (PLD) in growth plate chondrocytes by 24R,25
      (OH)2D3 is dependent on cell maturation state (resting zone cells) and is
      specific to the PLD2 isoform.
AB  - Many of the effects of 1alpha,25-(OH)2D3 and 24R,25-(OH)2D3 on costochondral
      chondrocytes are mediated by the protein kinase C (PKC) signal transduction
      pathway. 1alpha,25-(OH)2D3 activates PKC in costochondral growth zone
      chondrocytes through a specific membrane receptor (1alpha,25-mVDR), involving
      rapid increases in diacylglycerol via a phospholipase C (PLC)-dependent
      mechanism. 24R,25-(OH)2D3 activates PKC in resting zone chondrocytes. Although
      diacylglycerol is increased by 24R,25-(OH)2D3, PLC is not involved, suggesting a
      phospholipase D (PLD)-dependent mechanism. Here, we show that resting zone and
      growth zone cells express mRNAs for PLD1a, PLD1b, and PLD2. Both cell types have
      PLD activity, but levels are higher in resting zone cells. 24R,25-(OH)2D3, but
      not 24S,25-(OH)2D3 or 1alpha,25-(OH)2D3, stimulates PLD activity in resting zone
      cells within 3 min via nongenomic mechanisms. Neither 1alpha,25-(OH)2D3 nor
      24R,25-(OH)2D3 affected PLD in growth zone cells. Basal and 24R,25-(OH)2D3
      stimulated PLD were inhibited by the PLD inhibitors wortmannin and EDS.
      Inhibition of phosphatidylinositol 3-kinase (PI 3-kinase), PKC,
      phosphatidylinositol-specific PLC (PI-PLC), and phosphatidylcholine-specific PLC
      (PC-PLC) had no effect on PLD activity. Thus, 24R,25-(OH)2D3 stimulates PLD, and
      PI 3-kinase, PI-PLC and PKC are not involved, whereas PLD is required for
      stimulation of PKC by 24R,25-(OH)2D3. Pertussis toxin, GDPbetaS, and GTPgammaS
      had no effect on 24R,25-(OH)2D3-dependent PLD when added to cell cultures,
      indicating that G-proteins are not involved. These data show that PKC activation
      in resting zone cells is mediated by PLD and suggest that a functional 24R,25
      (OH)2D3-mVDR is required. The results also support the conclusion that the 24R,25
      (OH)2D3-responsive PLD is PLD2, since this PLD isoform is G-protein-independent.

PMID- 11341969
TI  - Functional testing of putative oligopeptide permease (Opp) proteins of Borrelia
      burgdorferi: a complementation model in opp(-) Escherichia coli.
AB  - Studies of the protein function of Borrelia burgdorferi have been limited by a
      lack of tools for manipulating borrelial DNA. We devised a system to study the
      function of a B. burgdorferi oligopeptide permease (Opp) orthologue by
      complementation with Escherichia coli Opp proteins. The Opp system of E. coli has
      been extensively studied and has well defined substrate specificities. The system
      is of interest in B. burgdorferi because analysis of its genome has revealed
      little identifiable machinery for synthesis or transport of amino acids and only
      a single intact peptide transporter operon. As such, peptide uptake may play a
      major role in nutrition for the organism. Substrate specificity for ABC peptide
      transporters in other organisms is determined by their substrate binding protein.
      The B. burgdorferi Opp operon differs from the E. coli Opp operon in that it has
      three separate substrate binding proteins, OppA-1, -2 and -3. In addition, B.
      burgdorferi has two OppA orthologues, OppA-4 and -5, encoded on separate
      plasmids. The substrate binding proteins interact with integral membrane
      proteins, OppB and OppC, to transport peptides into the cell. The process is
      driven by two ATP binding proteins, OppD and OppF. Using opp-deleted E. coli
      mutants, we transformed cells with B. burgdorferi oppA-1, -2, -4 or -5 and E.
      coli oppBCDF. All of the B. burgdorferi OppA proteins are able to complement E.
      coli OppBCDF to form a functional Opp transport system capable of transporting
      peptides for nutritional use. Although there is overlap in substrate
      specificities, the substrate specificities for B. burgdorferi OppAs are not
      identical to that of E. coli OppA. Transport of toxic peptides by B. burgdorferi
      grown in nutrient-rich medium parallels borrelial OppA substrate specificity in
      the complementation system. Use of this complementation system will pave the way
      for more detailed studies of B. burgdorferi peptide transport than currently
      available tools for manipulating borrelial DNA will allow.

PMID- 11341970
TI  - Modulation of alpha2beta1 integrin changes during mammary gland development by
      beta-oestradiol.
AB  - In order to study the role of cell-matrix interactions in mammary gland function,
      temporal changes in alpha2beta1 integrin, the major receptor for collagen and the
      influence of beta-oestradiol on its level and distribution in rat mammary gland
      at different stages of development were studied. The level of alpha2beta1
      integrin determined by ELISA, was found to be high during different days of
      pregnancy, while in the lactating stage, it was significantly reduced. By
      immunocytochemical analysis, alpha2beta1 integrin was found to be localized
      towards the luminal side of acinar cells, both in the virgin and midpregnant
      stage, while it was not detected in the lactating stage. The possible role of
      hormones in modulating the level of integrin was examined in both in vitro and in
      vivo experiments using beta-oestradiol. Supplementing beta-oestradiol to isolated
      mammary epithelial cells from both virgin and lactating glands caused a
      concentration dependent increase in the incorporation of [35S]methionine into
      alpha2beta1 integrin associated with the cells. Administration of beta-oestradiol
      to virgin and lactating glands caused about 1.4-4-fold increase in the level of
      alpha2 integrin, indicating that upregulation of integrin during pregnancy may be
      due to oestrogen and as the oestrogen level falls during lactating phase,
      downregulation of alpha2beta1 integrin occurs. Treatment with beta-oestradiol
      also resulted in the appearance of alpha2beta1 integrin in the acinar region of
      the lactating tissue, while in the untreated controls no staining for integrin
      was seen. These results indicate that oestrogen, apart from directly affecting
      the cellular activity, can influence mammary tissue function by affecting cell
      ECM interactions through the modulation of integrin receptors for matrix
      proteins.

PMID- 11341971
TI  - Growth condition-dependent synchronized changes in transcript levels of type II
      hexokinase and type 1 glucose transporter in tumor cells.
AB  - Transcript levels of hexokinase (HK) isozymes and glucose transporter (GLUT)
      isoforms in RNA samples of AH130 cells obtained from dish cultures and ascites
      were evaluated in a quantitative manner. In AH130 cells cultured in dishes, HKI
      and HKII were expressed at a similar level, but HKIII and HKIV were not. GLUT1
      and GLUT3 were also expressed, and messages of these two isoforms represented 27%
      and 71%, respectively, of the total GLUT messages. A faint signal of GLUT2 was
      also observed. On the contrary, in cells grown as ascites, the transcript of HKII
      was dominant, and its level was about 15-fold over that of dish-cultured AH130
      cells. Transcript levels of GLUT1 and GLUT3 were 4.5- and 2-fold, respectively,
      higher than those in dish-cultured cells. Thus, GLUT1 was more susceptible to
      changes in culture conditions than GLUT3. Based on these results, we concluded
      that the change in growth conditions caused synchronized changes in the
      transcript levels of HKII and GLUT1 in AH130 cells. However, such marked changes
      in the transcript levels of HKII and GLUT1 were not observed when AH130 cells
      were cultured in dishes under a hypoxic condition, indicating that the observed
      changes were not solely attributable to the difference in oxygen concentration
      between the ascites and cell culture conditions. Accordingly, other factors such
      as growth factors may be responsible for this difference in levels of HKII and
      GLUT1 between the two growth conditions.

PMID- 11341972
TI  - Increased uncoupling protein-2 gene expression in brain of lipopolysaccharide
      injected mice: role of tumour necrosis factor-alpha?
AB  - In order to understand the role of brain localized uncoupling proteins, we have
      examined the UCP2 and BMCP-1 gene expression in mice brain in two different
      catabolic states: administration of lipopolysaccharide (LPS) (2.5 mg/kg, i.p.)
      and tumour burden. Administration of LPS resulted in an increased UCP2 gene
      expression both in brain (208%) and cerebellum (77%). An increase in UCP2 gene
      expression was also observed after LPS treatment in double knockout mice for
      tumour necrosis factor-alpha (TNF) receptors 1 and 2 (75% in brain and 33% in
      cerebellum). Tumour growth also resulted in increased brain UCP2 gene expression
      (80%) in mice bearing the Lewis lung carcinoma as compared with the non-tumour
      bearing controls. No changes were observed in BMCP-1 mRNA levels of either LPS
      injected or tumour-bearing mice. From the results presented it may be suggested
      that: (a) the brain may contribute significantly to the increase in energy
      expenditure associated with hypermetabolic states such as fever and tumour
      burden, and (b) the regulation of UCP2 gene expression in brain does not seem to
      be influenced by TNF; therefore the action of other cytokines cannot be
      discarded.

PMID- 11341973
TI  - N1E-115 mouse neuroblastoma cells express MT1 melatonin receptors and produce
      neurites in response to melatonin.
AB  - Melatonin, a pineal hormone that induces sleep, has become a popular over-the
      counter drug. The cellular effects of melatonin, however, are only beginning to
      be studied. We have recently shown that stimulation of the MT1 melatonin receptor
      induces rapid and dramatic cytoskeletal rearrangements in transformed non
      neuronal cells (Witt-Enderby et al., Cell. Motil. Cytoskel. 46 (2000) 28). These
      cytoskeletal changes result in the formation of structures that closely resemble
      neurites. In this work, we show that the N1E-115 mouse neuroblastoma cell line
      rapidly responds to melatonin stimulation and forms neurites within 24 h. We also
      demonstrate that these cells readily bind 2-[125I]iodomelatonin at levels
      consistent with what is noted for native tissues (B(max)=3.43+/-1.56 fmol/mg
      protein; K(d)=240 pM). Western analysis shows that these cells possess and
      express melatonin receptors of the MT1 subtype. Treatment with pertussis toxin
      eliminates neurite formation whereas treatment with the MT2 subtype-specific
      activator, BMNEP, does not induce neurite formation. We have previously shown
      that increases in MEK 1/2 and ERK 1/2 phosphorylation are correlated with the
      shape changes in transformed CHO cells. Western analysis of the MEK/ERK signaling
      pathway in N1E-115 cells shows that this pathway is most likely maximally and
      constitutively stimulated. This may account for the spontaneous production of
      neurites noted for this cell line after long culture periods. The results of this
      work show that melatonin receptor stimulation in a neuronal cell type results in
      the formation of neurites and that the receptors responsible for melatonin
      induced neurite formation in N1E-115 cells are most likely of the MT1 subtype.

PMID- 11341974
TI  - Docosahexaenoic acid induces apoptosis in Jurkat cells by a protein phosphatase
      mediated process.
AB  - Docosahexaenoic acid (DHA) is an omega-3 fatty acid under intense investigation
      for its ability to modulate cancer cell growth and survival. This research was
      performed to study the cellular and molecular effects of DHA. Our experiments
      indicated that the treatment of Jurkat cells with DHA inhibited their survival,
      whereas similar concentrations (60 and 90 microM) of arachidonic acid and oleic
      acid had little effect. To explore the mechanism of inhibition, we used several
      measures of apoptosis to determine whether this process was involved in DHA
      induced cell death in Jurkat cells. Caspase-3, an important cytosolic downstream
      regulator of apoptosis, is activated by death signals through proteolytic
      cleavage. Incubation of Jurkat cells with 60 and 90 microM DHA caused proteolysis
      of caspase-3 within 48 and 24 h, respectively. DHA treatment also caused the
      degradation of poly-ADP-ribose polymerase and DNA fragmentation as assayed by
      flow cytometric TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick
      end labeling) assay. These results indicate that DHA induces apoptosis in Jurkat
      leukemic cells. DHA-induced apoptosis was effectively inhibited by tautomycin and
      cypermethrin at concentrations that affect protein phosphatase 1 (PP1) and
      protein phosphatase 2B (PP2B) activities, respectively, implying a role for these
      phosphatases in the apoptotic pathway. Okadaic acid, an inhibitor of protein
      phosphatase 2A, had no effect on DHA-induced apoptosis. These results suggest
      that one mechanism through which DHA may control cancer cell growth is through
      apoptosis involving PP1/PP2B protein phosphatase activities.

PMID- 11341976
TI  - The Experts at Hadamar.

PMID- 11341977
TI  - Activation of extracellular-regulated kinases by normal and mutant EGF receptors.
AB  - Glioblastoma cells express a mutant EGF receptor (EGFRvIII) that has constitutive
      tyrosine kinase activity and enhances their tumorigenicity. Here we show that
      EGFRvIII promotes constitutive phosphorylation of extracellular regulated kinases
      (ERKs) in glioblastoma cells in the absence of EGF. EGFRvIII also promoted
      constitutive activation of phosphoinositide 3-kinase in these cells, as assessed
      by phosphorylation of protein kinase B/akt. As expected, phosphorylation of
      protein kinase B/akt was blocked by the phosphoinositide 3-kinase inhibitors
      wortmannin and LY294002. Less expectedly, we found that this treatment also
      blocked EGFRvIII-induced phosphorylation of ERKs. In contrast, ERK
      phosphorylation induced by EGF-activated normal EGF receptor in the same cells
      was largely unaffected by treatment with phosphoinositide 3-kinase inhibitors.
      This difference in behavior between the normal receptor and EGFRvIII was not due
      to differences in the levels of activated EGFRvIII and wild-type EGF receptor, as
      the two types of receptor were tyrosine phosphorylated to a similar extent under
      the experimental conditions used. EGFRvIII activation of ERKs was also sensitive
      to the phospholipase C inhibitor U73122, whereas ERK activation by normal EGF
      receptor was not. These results show that EGFRvIII and wild-type EGF receptor
      preferentially use different signaling pathways to induce ERK phosphorylation.
      The different mechanisms of ERK activation used by normal and mutant EGF
      receptors may be important in understanding the potent tumorigenic activity of
      EGFRvIII.

PMID- 11341978
TI  - Dynamin inhibits phosphatidylinositol 3-kinase in hematopoietic cells.
AB  - Phosphatidylinositol 3-kinase (PI 3-kinase) plays a role in late stages of
      endocytosis as well as in cellular proliferation and transformation. The SH3
      domain of its regulatory p85 subunit stimulates the GTPase activity of dynamin in
      vitro. Dynamin is a GTPase enzyme required for endocytosis of activated growth
      factor receptors. An interaction between these proteins has not been demonstrated
      in vivo. Here, we report that dynamin associates with PI 3-kinase in
      hematopoietic cells. We detected both p85 and PI 3-kinase activity in dynamin
      immune complexes from IL-3-dependent BaF3 cells. However, this association was
      significantly reduced in BaF3 cells transformed with the BCR/abl oncogene. After
      transformation only a 4-fold increase in PI 3-kinase activity was detected in
      dynamin immune complexes, whereas grb2 associated activity was elevated 20-fold.
      Furthermore, dynamin inhibited the activity of both purified recombinant and
      immunoprecipitated PI 3-kinase. In BaF3 cells expressing a temperature-sensitive
      mutant of BCR/abl, a significant decrease in p85 and dynamin association was
      observed 4 h after the induction of BCR/abl activity. In contrast, in IL-3
      stimulated parental BaF3 cells, this association was increased. Our results
      demonstrate an in vivo association of PI 3-kinase with dynamin and this
      interaction regulates the activity of PI 3-kinase.

PMID- 11341979
TI  - Osmotically induced cytosolic free Ca(2+) changes in human neutrophils.
AB  - Cytosolic free Ca(2+) concentration in neutrophils was measured by ratiometric
      fluorometry of intracellular fura2. Increasing the extracellular osmolarity, by
      either NaCl (300-600 mM) or sucrose (600-1200 mM), caused a rise in cytosolic
      free Ca(2+) (Delta(max) approximately equal to 600 nM). This was not due to cell
      lysis as the cytosolic free Ca(2+) concentration was reversed by restoration of
      isotonicity and a second rise in cytosolic free Ca(2+) could be provoked by
      repeating the change in extracellular osmolarity. Furthermore, the rise in
      cytosolic free Ca(2+) concentration occurred in the absence of extracellular
      Ca(2+), demonstrating that release of intracellular fura2 into the external
      medium did not occur. The osmotically-induced rise in cytosolic free Ca(2+) was
      not inhibited by either the phospholipase C-inhibitor U73122, or the
      microfilament inhibitor cytochalasin B, suggesting that neither signalling via
      inositol tris-phosphate or the cytoskeletal system were involved. However, the
      rise in cytosolic free Ca(2+) may have resulted from a reduction in neutrophil
      water volume in hyperosmotic conditions. As these rises in cytosolic Ca(2+)
      (Delta(max) approximately equal to 600 nM) were large enough to provoke changes
      in neutrophil activity, we propose that conditions which removes cell water may
      similarly elevate cytosolic free Ca(2+) to physiologically important levels.

PMID- 11341980
TI  - Electrical stimulation influences mineral formation of osteoblast-like cells in
      vitro.
AB  - The aim of the present study was to assess the structure of newly formed mineral
      crystals after electrical stimulation of osteoblast-like cells in vitro. Pulsed
      electrical stimulation was coupled capacitively or semi-capacitively to primary
      osteoblast-like cells derived from bovine metacarpals. Computer calculations
      revealed that the chosen input signal (saw-tooth, 100 V, 63 ms width, 16 Hz
      repetition rate) generated a short pulsed voltage drop of 100 microV (capacitive
      coupled mode) and of 350 microV (semi-capacitive coupled mode) across the cell
      matrix layer. Stimulated cultures showed an enhanced mineral formation compared
      to the non stimulated controls. In cultures exposed to capacitively coupled
      electric fields and in control cultures nodules and mineralized globules were
      found. Nodules with a diameter of less than 200 nm covered the cell surface,
      whereas mineral globules with a diameter of up to 700 nm formed characteristic
      mineral deposits in the vicinity of the cells similar to biomineral formations
      occurring in mineralizing tissues. In contrast, large rod-shaped crystals were
      found in cultures stimulated by semi-capacitive coupled electric fields,
      indicating a non-physiological precipitation process. In conclusion, osteoblasts
      in culture are sensitive to electrical stimulation resulting in an enhancement of
      the biomineralization process.

PMID- 11341981
TI  - Modulation of the stress response during apoptosis and necrosis induction in
      cadmium-treated U-937 human promonocytic cells.
AB  - Treatment for 2 h with 200 microM cadmium chloride, followed by recovery, caused
      apoptosis and induced heat-shock protein 70 (HSP70) expression in U-937
      promonocytic cells. However, pre-incubation with the GSH depleting agent L
      buthionine-[S,R]-sulfoximine (BSO, 1 mM for 24 h) caused necrosis instead of
      apoptosis and failed to induce HSP70 expression. This failure was a consequence
      of necrosis instead of GSH depletion, since BSO allowed or even potentiated HSP70
      induction when used in combination with heat shock (2 h at 42.5 degrees C) or
      with 50 microM cadmium, which caused apoptosis. The administration of N-acetyl-L
      cysteine (NAC) at the beginning of recovery after BSO/200 microM cadmium
      treatment prevented the execution of necrosis and restored the execution of
      apoptosis, but did not restore HSP70 induction, indicating that the inhibition by
      BSO of HSP70 expression is an early regulated event. This contrasted with the
      capacity of NAC to prevent the alterations caused by BSO/200 microM cadmium in
      other proteins, namely the suppression of Bax expression and the increase in Bcl
      2 and HSP-60 expression. Finally, it was observed that treatment with 200 microM
      cadmium rapidly increased the HSP70 mRNA level and stimulated heat-shock factor 1
      (HSF1) trimerization and binding, and that these effects were prevented by pre
      incubation with BSO. Taken together, these results indicate that the stress
      response is compatible with apoptosis but not with necrosis in cadmium-treated
      promonocytic cells. The suppression of the stress response is specifically due to
      the early inhibition of HSF1 activation.

PMID- 11341982
TI  - Distinct patterns of insulin-like growth factor binding protein (IGFBP)-2 and
      IGFBP-3 expression in oxidant exposed lung epithelial cells.
AB  - Oxygen (O(2)) species are involved in a large variety of pulmonary diseases.
      Among the various cell types that compose the lung, the epithelial cells of the
      alveolar structure appear to be a major target for oxidant injury. Despite their
      importance in the repair processes, the mechanisms which regulate the replication
      of the stem cells of the alveolar epithelium, the type 2 cells, remain poorly
      understood. Based on the results of several studies which have documented the
      involvement of the insulin-like growth factor (IGF) system in lung epithelial
      cell replication, and which have also suggested a role for IGF binding proteins
      (IGFBPs) in the control of cell proliferation, the aim of the present work was to
      determine whether IGFBPs could be involved in the modulation of growth of human
      lung epithelial cells exposed to oxidants. Experiments were performed using a
      human lung adenocarcinoma cell line (A549) which was exposed for various
      durations to hyperoxia (95% O(2)). We observed a rapid and reversible growth
      arrest of the cells after only 24 h of O(2) exposure. When oxidant injury was
      prolonged, growth arrest was followed by induction of apoptosis with activation
      of the Fas pathway. These effects were associated with an increased expression of
      IGFBP-2 and IGFBP-3. In addition, study of localization of these proteins
      revealed distinct patterns of distribution. IGFBP-3 was mainly present in the
      extracellular compartment. In comparison, the fraction of IGFBP-2 secreted was
      less abundant whereas the IGFBP-2 fraction in the intracellular compartment
      appeared stronger. In addition, analysis of the subcellular localization provided
      data indicating the presence of IGFBP-2 in the nucleus. Taken together these data
      support a role for IGFBP-2 and IGFBP-3 in the processes of growth arrest and
      apoptosis in lung epithelial cells upon oxidant exposure. They also suggest that
      distinct mechanisms may link IGFBP-2 and IGFBP-3 to the key regulators of the
      cell cycle.

PMID- 11341983
TI  - HCV core protein modulates Rb pathway through pRb down-regulation and E2F-1 up
      regulation.
AB  - It has been recognized that the HCV (hepatitis C virus) core protein plays an
      important role in hepatocarcinogenesis. The functional inactivation of the Rb
      pathway appears to be a major event for multi-step cancer carcinogenesis. To
      elucidate the role of the HCV core protein in hepatocarcinogenesis, we
      investigated the effect of the HCV core protein on the Rb pathway in both Rat-1
      cell lines, stably expressing the HCV core protein and the doxycycline-regulated
      cell lines. The HCV core stable transfectants showed a dramatic decrease in the
      pRb levels and E2F-1 up-regulation. In the doxycycline-regulated cell lines, the
      pRb levels were significantly decreased which are followed by E2F-1 up
      regulation. HCV core stable transfectants showed higher cell growth rates and
      were sensitize to apoptosis. Thus, our results first indicate that the HCV core
      protein decreases the expression of pRb, thereby allowing E2F-1 to be
      constitutively active, which is thought to result in rapid cell proliferation or
      sensitizing to apoptosis.

PMID- 11341984
TI  - Zinc affects the conformation of nucleoprotein filaments formed by replication
      protein A (RPA) and long natural DNA molecules.
AB  - Replication protein A is the major single strand DNA binding protein of human
      cells, composed of three subunits with molecular weights of 70, 32, and 14 kDa.
      Most of the DNA binding activity of RPA has been mapped to the largest subunit
      that contains two OB-fold DNA binding domains and a third, OB-like structure in
      the carboxyterminal domain (CTD). This third domain resembles an OB-fold with a
      zinc binding domain inserted in the middle of the structure, and has recently
      been shown to carry a coordinated Zn(II) ion. The bound metal ion is essential
      for the tertiary structure of the RPA70-CTD, and appears to modulate its DNA
      binding activity when tested with synthetic oligonucleotides. We show here that
      zinc strongly affects the conformation of nucleoprotein filaments formed between
      RPA and long natural DNA molecules. In these experiments, the CTD is dispensable
      for DNA binding and the unwinding of long double stranded DNA molecules. However,
      using band shift assays and electron microscopy, we found that RPA-DNA complexes
      contract at zinc concentrations that do not affect the conformations of complexes
      formed between DNA and a RPA70 deletion construct lacking the CTD. Our data
      suggest that nucleoprotein complexes with RPA in its natural, zinc-bearing form
      may have a compact rather than an extended conformation.

PMID- 11341985
TI  - Influence of proteasome and redox state on heat shock-induced activation of
      stress kinases, AP-1 and HSF.
AB  - We studied the pattern of activation of stress kinases and of transcription
      factors activator protein-1 (AP-1) and heat shock factor (HSF) in FAO cells by
      combining two treatments, i.e. heating (42 degrees C for 1 h) and proteasome
      inhibition, each known to cause cellular heat shock response. The co-treatment
      heat shock (HS) and proteasome inhibitor (a peptidyl aldehyde or lactacystin)
      showed cumulative effects on the intensity and duration of activation of c-Jun N
      terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) at the end
      of the HS period and during recovery. Similarly, the thiol-reducing agents N-(2
      mercaptoethyl)-1,3-diaminopropane and dithiothreitol strongly activated both JNK
      and p38 MAPK in cells undergoing HS. AP-1 DNA binding activity in response to
      proteasome inhibitors was so strong that it shadowed the stimulatory effect of HS
      in the combined treatment, but lactacystin, which is the most potent and specific
      proteasome inhibitor, decreased the binding late during recovery from HS. Thiol
      reducing agents prevented AP-1 DNA binding induced by HS. The combined
      HS/proteasome inhibitors or HS/thiol-reducing agents treatments cooperatively
      activated HSF DNA binding. Expression of collagenase I and hsp 70 mRNAs reflects
      the different behavior of AP-1 and HSF transcription factors in cells exposed to
      HS and proteasome inhibition. The data seem to indicate that JNK and p38 MAPK
      activations are not necessarily coupled to DNA binding of AP-1, which can be
      either increased or inhibited when these kinases are activated. AP-1 and HSF show
      opposite patterns of response to HS in the presence of proteasome inhibitors or
      reducing agents.

PMID- 11341987
TI  - Erratum to "Quantitative analysis of polymorphs in binary and multi-component
      powder mixtures by near-infrared reflectance spectroscopy".

PMID- 11341986
TI  - Growth arrest in A549 cells during hyperoxic stress is associated with decreased
      cyclin B1 and increased p21(Waf1/Cip1/Sdi1) levels.
AB  - Exposure to high concentrations of oxygen has previously been shown to cause
      growth arrest in A549 cells, a distal lung epithelial cell line. We found that
      when A549 cells were exposed to 95% oxygen they underwent substantial growth
      inhibition. This was associated with induction of p21(Waf1/Cip1/Sdi1) protein and
      a decrease in cyclin B1 protein. Flow cytometry revealed that A549 cells exposed
      to hyperoxia had a significant decrease in the percentage of cells in G(1) and a
      modest but significant increase in the percentage of cells in S phase and G(2)/M,
      consistent with cells entering S phase. A549 cells in room air and hyperoxia were
      then treated with nocodazole, a mitotic inhibitor. Room air A549 cells treated
      with nocodazole showed a marked increase in G(2)/M consistent with mitotic
      arrest. In contrast, hyperoxic treated cells had a modest but significant
      decrease in G(1) but only a minimal increase in G(2)/M consistent with partial
      G(1)/S arrest and growth inhibition in S phase. To further investigate the role
      of p21(Waf1/Cip1/Sdi1) as a checkpoint regulator during hyperoxic growth
      inhibition, HCT116 cells with wild-type and null p21(Waf1/Cip1/Sdi1) were exposed
      to hyperoxia. Both wild-type p21(+/+) cells and null p21(-/-) cells underwent
      growth inhibition when exposed to hyperoxia. At 48 h the hyperoxic treated HCT116
      p21(+/+) had a similar cell cycle distribution as the hyperoxic treated HCT116
      p21(-/-) cells, suggesting that p21(Waf1/Cip1/Sdi1) may not be essential for
      growth arrest during hyperoxia. These findings suggest that hyperoxia causes
      partial growth arrest at different phases of the cell cycle but primarily in S
      phase, that hyperoxic growth arrest is associated with a decrease in cyclin B1
      protein and that p21 induction may not be essential for hyperoxic growth arrest.

PMID- 11341989
TI  - Controlling the efficiency of excision repair.
AB  - The early studies are recounted, that led to the discovery of the ubiquitous
      process of DNA excision repair, followed by a review of the pathways of
      transcription-coupled repair (TCR) and global genomic nucleotide excision repair
      (GGR). Repair replication of damaged DNA in UV-irradiated bacteria was discovered
      through the use of 5-bromouracil to density-label newly synthesized DNA. This
      assay was then used in human cells to validate the phenomenon of unscheduled DNA
      synthesis as a measure of excision repair and to elucidate the first example of a
      DNA repair disorder, xeroderma pigmentosum. Features of the TCR pathway (that is
      defective in Cockayne syndrome (CS)) include the possibility of "gratuitous TCR"
      at transcription pause sites in undamaged DNA. The GGR pathway is shown to be
      controlled through the SOS stress response in E. coli and through the activated
      product of the p53 tumor suppressor gene in human cells. These regulatory systems
      particularly affect the efficiency of repair of the predominant UV-induced
      photoproduct, the cyclobutane pyrimidine dimer, as well as that of chemical
      carcinogen adducts, such as benzo(a)pyrene diol-epoxide. Rodent cells (typically
      lacking the p53-controlled GGR pathway) and tumor virus infected human cells (in
      which p53 function is abrogated) are unable to carry out efficient GGR of some
      lesions. Therefore, caution should be exercised in the interpretation of results
      from such systems for risk assessment in genetic toxicology. Many problems in
      excision repair remain to be solved, including the mechanism of scanning the DNA
      for lesions and the subcellular localization of the repair factories. Also there
      are persisting questions regarding the multiple options of repair, recombination,
      and translesion synthesis when replication forks encounter lesions in the
      template DNA. That is where the field of DNA excision repair began four decades
      ago with studies on the recovery of DNA synthesis in UV-irradiated bacteria.

PMID- 11341990
TI  - Gene and sequence specificity of DNA damage induction and repair: consequences
      for mutagenesis.
AB  - The field of DNA repair has been expanded enormously in the last 20 years. In
      this paper, work on gene and sequence specificity of DNA damage induction and
      repair is summarized in the light of the large and broad contribution of Phil
      Hanawalt to this field of research. Furthermore, the consequences of DNA damage
      and repair for mutation induction is discussed, and the contribution of Paul
      Lohman to the development of assays employing transgenic mice for the detection
      of gene mutations is highlighted.

PMID- 11341991
TI  - Nucleotide excision repair "a legacy of creativity".
AB  - The first half of the 20th century has seen an enormous growth in our knowledge
      of DNA repair, in no small part due to the work of Dirk Bootsma, Philip Hanawalt
      and Bryn Bridges; those honored by this issue. For the new millennium, we have
      asked three general questions: (A) Do we know all possible strategies of
      nucleotide excision repair (NER) in all organisms? (B) How is NER integrated and
      regulated in cells and tissues? (C) Does DNA replication represent a new frontier
      in the roles of DNA repair? We make some suggestions for the kinds of answers the
      next generation may provide. The kingdom of archea represents an untapped field
      for investigation of DNA repair in organisms with extreme lifestyles. NER appears
      to involve a similar strategy to the other kingdoms of prokaryotes and
      eukaryotes, but subtle differences suggest that individual components of the
      system may differ. NER appears to be regulated by several major factors,
      especially p53 and Rb which interact with transcription coupled repair and global
      genomic repair, respectively. Examples can be found of major regulatory changes
      in repair in testicular tissue and melanoma cells. Our understanding of
      replication of damaged DNA has undergone a revolution in recent years, with the
      discovery of multiple low-fidelity DNA polymerases that facilitate replicative
      bypass. A secondary mechanism of replication in the absence of NER or of one or
      more of these polymerases involves sister chromatid exchange and recombination
      (hMre11/hRad50/Nbs1). The relative importance of bypass and recombination is
      determined by the action of p53. We hypothesise that these polymerases may be
      involved in resolution of complex DNA structures during completion of replication
      and sister chromatid resolution. With these fascinating problems to investigate,
      the field of DNA repair will surely not disappoint the next generation.

PMID- 11341992
TI  - The "Dutch DNA Repair Group", in retrospect.
AB  - The "Dutch DNA Repair Group" was established about 35 years ago. In this brief
      historical review some of the crucial decisions are described that have
      contributed to the relative success of the research of this group. The emphasis
      of the work of this group has been for many years on the genetic analysis of
      nucleotide excision repair (NER) and genetic diseases based on defects in this
      repair process: xeroderma pigmentosum (XP), Cockayne syndrome and
      trichothiodystrophy.

PMID- 11341993
TI  - From xeroderma pigmentosum to the biological clock contributions of Dirk Bootsma
      to human genetics.
AB  - This paper commemorates the multiple contributions of Dirk Bootsma to human
      genetics. During a scientific 'Bootsma' cruise on his sailing-boat 'de Losbol',
      we visit a variety of scenery locations along the lakes and canals in Friesland,
      passing the highlights of Dirk Bootsma's scientific oeuvre. Departing from 'de
      Fluessen', his homeport, with his PhD work on the effect of X-rays and UV on cell
      cycle progression, we head for the pioneering endeavours of his team on mapping
      genes on human chromosomes by cell hybridization. Next we explore the use of cell
      hybrids by the Bootsma team culminating in the molecular cloning of one of the
      first chromosomal breakpoints involved in oncogenesis: the bcr-abl fusion gene
      responsible for chronic myelocytic leukemia. This seminal achievement enabled
      later development of new methods for early detection and very promising
      therapeutic intervention. A series of highlights at the horizon constitute the
      contributions of his team to the field of DNA repair, beginning with the
      discovery of genetic heterogeneity in the repair syndrome xeroderma pigmentosum
      (XP) followed later by the cloning of a large number of human repair genes. This
      led to the discovery that DNA repair is strongly conserved in evolution rendering
      knowledge from yeast relevant for mammals and vice versa. In addition, it
      resolved the molecular basis of several repair syndromes and permitted functional
      analysis of the encoded proteins. Another milestone is the discovery of the
      surprising connection between DNA repair and transcription initiation via the
      dual functional TFIIH complex in collaboration with Jean-Marc Egly et al. in
      Strasbourg. This provided an explanation for many puzzling clinical features and
      triggered a novel concept in human genetics: the existence of
      repair/transcription syndromes. The generation of many mouse mutants carrying
      defects in repair pathways yielded valuable models for assessing the clinical
      relevance of DNA repair including carcinogenesis and the identification of a link
      between DNA damage and premature aging. His team also opened a fascinating area
      of cell biology with the analysis of repair and transcription in living cells. A
      final surprising evolutionary twist was the discovery that photolyases designed
      for the light-dependent repair of UV-induced DNA lesions appeared to be adopted
      for driving the mammalian biological clock. The latter indicates that it is time
      to return to 'de Fluessen', where we will consider briefly the merits of Dirk
      Bootsma for Dutch science in general.

PMID- 11341994
TI  - The two-step model for translesion synthesis: then and now.
AB  - The formation of base substitution mutations following exposure of bacteria to
      ultraviolet light and many other mutagens occurs during translesion synthesis
      opposite a photoproduct or other lesion in the template strand of DNA. This
      process requires the UmuD(2)' UmuC complex, only formed to a significant extent
      in SOS-induced cells. The "two-step" model proposed that there were two steps,
      insertion of a wrong base (misincorporation) and use of the misincorporated base
      as a primer for further chain extension (bypass). The original evidence suggested
      that UmuD(2)' UmuC was needed only for the second step and that in its absence
      other polymerases such as DNA polymerase III could make misincorporations. Now we
      know that the UmuD(2)' UmuC complex is DNA polymerase V and that it can carry out
      both steps in vitro and probably does both in vivo in wild-type cells. Even so,
      DNA polymerase III clearly has an important accessory role in vitro and a
      possibly essential role in vivo, the precise nature of which is not clear. DNA
      polymerases II and IV are also up-regulated in SOS-induced cells and their
      involvement in the broader picture of translesion synthesis is only now beginning
      to emerge. It is suggested that we need to think of the chromosomal replication
      factory as a structure through which the DNA passes and within which as many as
      five DNA polymerases may need to act. Protein-protein interactions may result in
      a cassette system in which the most appropriate polymerase can be engaged with
      the DNA at any given time. The original two-step model was very specific, and
      thus an oversimplification. As a general concept, however, it reflects reality
      and has been demonstrated in experiments with eukaryotic DNA polymerases in
      vitro.

PMID- 11341995
TI  - Bryn Bridges and mutagenesis: exploring the intellectual space.
AB  - The products of the SOS-regulated umuDC genes are required for most UV and
      chemical mutagenesis in Escherichia coli. Recently it has been recognized that
      UmuC is the founding member of a superfamily of novel DNA polymerases found in
      all three kingdoms of life. Key findings leading to these insights are reviewed,
      placing a particular emphasis on contributions made by Bryn Bridges and on his
      interest in the importance of interactions between the umuDC gene products and
      the replicative DNA polymerase.

PMID- 11341996
TI  - Evolution of the two-step model for UV-mutagenesis.
AB  - It is quite remarkable how our understanding of translesion DNA synthesis (TLS)
      has changed so dramatically in the past 2 years. Until very recently, little was
      known about the molecular mechanisms of TLS in higher eukaryotes and what we did
      know, was largely based upon Escherichia coli and Saccharomyces cerevisiae model
      systems. The paradigm, proposed by Bryn Bridges and I [Mutat. Res. 150 (1985)
      133] in 1985, was that error-prone TLS occurred in two steps; namely a
      misinsertion event opposite a lesion, followed by extension of the mispair so as
      to facilitate complete bypass of the lesion. The initial concept was that at
      least for E. coli, the misinsertion event was performed by the cell's main
      replicase, DNA polymerase III holoenzyme, and that elongation was achieved
      through the actions of specialized polymerase accessory proteins, such as UmuD
      and UmuC. Some 15 years later, we now know that this view is likely to be
      incorrect in that both misinsertion and bypass are performed by the Umu proteins
      (now called pol V). As pol V is normally a distributive enzyme, pol III may only
      be required to "fix" the misincorporation as a mutation by completing chromosome
      duplication. However, while the role of the E. coli proteins involved in TLS have
      changed, the initial concept of misincorporation followed by extension/bypass
      remains valid. Indeed, recent evidence suggests that it can equally be applied to
      TLS in eukaryotic cells where there are many more DNA polymerases to choose from.
      The aim of this review is, therefore, to provide a historical perspective to the
      "two-step" model for UV-mutagenesis, how it has recently evolved, and in
      particular, to highlight the seminal contributions made to it by Bryn Bridges.

PMID- 11341997
TI  - Phenotype determination of anti-GM3 positive cells in atherosclerotic lesions of
      the human aorta. Hypothetical role of ganglioside GM3 in foam cell formation.
AB  - Earlier we reported that atherosclerotic plaques contain cells which were
      specifically and very intensively stained with anti-GM3 antibodies although no
      GM3 positive cells were detected in the normal non-diseased arterial intima.
      Because of their lipid inclusions, GM3 positive cells in atherosclerotic lesions
      seemed to be foam cells but their origin needed clarification. Using an
      immunohistochemical technique in the present work, we showed that some of these
      foam cells contained CD68 antigen. However, the most intense accumulation of GM3
      occurred in the areas composed of foam cells which did not stain with any cell
      type-specific antibodies, including antibodies to macrophages (anti-CD68) and
      smooth muscle cells (anti-smooth muscle alpha-actin), perhaps, because the cell
      type-specific antigens were lost during the transformation of intimal cells into
      foam cells. Ultrastructural analysis of the areas where foam cells overexpressed
      GM3 demonstrated that some foam cells lacked both a basal membrane and
      myofilaments but contained a large number of secondary lysosomes and
      phagolysosomes, morphological features which might indicate their macrophage
      origin. Other foam cells contained a few myofilaments and fragments of basal
      membrane around their plasmalemmal membrane, suggesting a smooth muscle cell
      origin. These observations indicate that accumulation of excessive amounts of GM3
      occurs in different cell types transforming into foam cells. We suggest that up
      regulation of GM3 synthesis in intimal cells might be an essential event in foam
      cell formation. Shedding of a large number of membrane-bound microvesicles from
      the cell surface of foam cells was observed in areas of atherosclerotic lesions
      corresponding to extracellular GM3 accumulation. We speculate that
      extracellularly localised GM3 might affect the differentiation and modification
      of intimal cells in atherosclerotic lesions.

PMID- 11341998
TI  - Inhibitory effects of tumor necrosis factor-alpha on cationic lipid-mediated gene
      delivery to airway cells in vitro.
AB  - Cationic liposomes have been used successfully for DNA delivery to airway cells
      in vitro and are being tested in human clinical trials for their efficacy in
      cystic fibrosis transmembrane conductance regulator (CFTR) gene delivery in
      cystic fibrosis patients. While cationic liposomes are effective for transfection
      of airway cells in culture, they have not been effectively used for gene delivery
      to human airway cells in vivo. Several barriers in cystic fibrosis lungs,
      including increased amounts of mucus, phagocytic cell activity and cytokine-rich
      milieu caused by inflammation, may cause inhibition of gene transfection. As
      presented in this paper, we examined the effects of inflammatory cytokines on
      cationic lipid-mediated transfection of model airway cells. The results of these
      experiments indicate that tumor necrosis factor (TNF)-alpha dramatically inhibits
      Lipofectin-mediated transfection efficiency of H441 cells. Addition of anti-TNF
      alpha neutralizing antibody results in recovery of efficiency. Results of
      temporal studies are consistent with the concept that TNF-alpha reduces
      transfection efficiency by a mechanism(s) other than or in addition to gene
      expression. These results are corroborated by fluorescence microscopic
      experiments which demonstrate that endocytosis of lipoplex is altered in the
      presence of TNF-alpha.

PMID- 11341999
TI  - Inhibitors of advanced glycation end product-associated protein cross-linking.
AB  - The reaction of lens proteins with sugars over time results in the formation of
      protein-bound advanced glycation end products (AGEs). The most damaging element
      of AGE formation may be the synthesis of protein-protein cross-links in long
      lived proteins, such as collagen or lens crystallins. A quantitative cross
      linking assay, involving the sugar-dependent incorporation of [U-(14)C]lysine
      into protein, was employed to determine the efficacy of a variety of potential
      cross-linking inhibitors. Reaction mixtures contained 5.0 mM L-threose, 2.5
      microCi [(14)C]lysine (1.0 mCi/mmole), 5.0 mg/ml bovine lens proteins, 0-10 mM
      inhibitor and 1.0 mM DTPA in 100 mM phosphate buffer, pH 7.0. Of 17 potential
      inhibitors tested, 11 showed 50% inhibition or less at 10 mM. The dicarbonyl
      reactive compounds 2-aminoguanidine, semicarbazide and o-phenylenediamine
      inhibited 50% at 2.0 mM, whereas 10 mM dimethylguanidine had no effect. Several
      amino acids failed to compete effectively with [(14)C]lysine in the cross-linking
      assay; however, cysteine inhibited 50% at 1.0 mM. This was likely due to the
      sulfhydryl group of cysteine, because 3-mercaptopropionic acid and reduced
      glutathione exhibited similar activity. Sodium metabisulfite had the highest
      activity, inhibiting 50% at only 0.1-0.2 mM. Protein dimer formation, as
      determined by SDS-PAGE, was inhibited in a quantitatively similar manner. The
      dicarbonyl-reactive inhibitors and the sulfur-containing compounds produced
      similar inhibition curves for [(14)C]lysine incorporation over a 3 week assay
      with 250 mM glucose. A much lesser effect was observed on either the
      incorporation of [(14)C]glucose, or on fluorophore formation (360/420 nm),
      suggesting that non-cross-link fluorophores were also formed. The inhibitor data
      were consistent with cross-linking by a dicarbonyl intermediate. This was
      supported by the fact that the inhibitors were uniformly less effective when the
      5.0 mM threose was replaced by either 3.0 mM 3-deoxythreosone or 3.0 mM
      threosone.

PMID- 11342000
TI  - The phorbol ester PMA and cyclic AMP activate different Cl(-) and HCO3(-) fluxes
      in C127 cells expressing CFTR.
AB  - In mouse mammary epithelial C127 cells expressing wild-type cystic fibrosis
      transmembrane conductance regulator (CFTR), chloride efflux, measured with the
      Cl(-)-sensitive dye 6-methoxy-N-(3-sulfopropyl)quinolinium (SPQ), was stimulated
      by activation of protein kinase A with cyclic AMP elevating agents forskolin plus
      3-isobutyl-1-methyl-xanthine (IBMX) and, to a less extent, by activation of
      protein kinase C with the phorbol 12-myristate 13-acetate (PMA). Conversely,
      bicarbonate influx, determined by intracellular alkalinization of cells incubated
      with the pH-sensitive dye 2',7'-bis(2-carboxyethyl)-5(6)
      carboxyfluoresceintetraacetoxymethyl ester (BCECF-AM), was stimulated by cyclic
      AMP elevation, but not by PMA. Patch clamp analysis revealed that PMA activated a
      Cl(-) current with the typical biophysical characteristics of swelling-activated
      current and not of CFTR.

PMID- 11342001
TI  - Oligomerization of Escherichia coli enterotoxin b through its C-terminal
      hydrophobic alpha-helix.
AB  - Using a chemical cross-linker and gel electrophoresis or a dot blot overlay
      assay, we studied protein-protein interaction of STb toxin, a 48-residue
      amphiphilic polypeptide causing intestinal disorders. For the first time, we
      report on the oligomerization property of STb. This enterotoxin forms hexamers
      and heptamers in a temperature-independent fashion in presence or absence of its
      receptor (sulfatide) anchored in a 50-nm liposome or as a free molecule. Full STb
      structure integrity is necessary for its oligomerization as this process is not
      observed under reducing conditions in the presence of beta-mercaptoethanol. STb
      treatment with tetramethylurea (TMU) and different detergents prevented
      oligomerization. Site-directed mutagenesis decreasing overall STb hydrophobicity
      in the hydrophobic alpha-helix resulted in the incapacity to form oligomers.
      Taken together, these data suggest that the C-terminal hydrophobic alpha-helix
      corresponds to the domain of STb-STb inter-binding where hydrophobic interaction
      is involved.

PMID- 11342002
TI  - Apolipoprotein E acts to increase nitric oxide production in macrophages by
      stimulating arginine transport.
AB  - Previous studies have shown that apolipoprotein E (apoE) plays a role in immune
      function by modulating tissue redox balance. Using a mouse macrophage cell line
      (RAW 264.7), we have examined the mechanism by which apoE regulates nitric oxide
      (NO) production in macrophages. ApoE potentiates NO production in immune
      activated RAW cells in combination with lipopolysaccharide or
      polyinosinic:polycytidylic acid (PIC), agents known to induce expression of
      inducible nitric oxide synthase mRNA and protein. The effect is not observed with
      apolipoprotein B or heat-inactivated apoE. The combination of PIC plus apoE
      produced more NO than the level expected from an additive effect of PIC and apoE
      alone. Furthermore, this increase was observed at submaximal extracellular
      arginine concentrations, suggesting that apoE altered arginine (substrate)
      availability. Examination of [(3)H]arginine uptake across the cell membrane
      demonstrated that arginine uptake was increased by PIC but further increased by
      PIC plus apoE. Treatment of RAW cells with apoE was associated with an increased
      apparent V(max) and decreased affinity for arginine as well as a switch in the
      induction of mRNA for subtypes of cationic amino acid transporters (CAT).
      Treatment of RAW cells with PIC plus apoE resulted in the loss of detectable CAT1
      mRNA and expression of CAT2 mRNA. Regulation of arginine availability is a novel
      action of apoE on the regulation of macrophage function and the immune response.

PMID- 11342003
TI  - Acrolein inhibits respiration in isolated brain mitochondria.
AB  - Lipid peroxidation is elevated in diseased regions of brain in several
      neurodegenerative diseases. Acrolein (2-propenal) is a major cytotoxic product of
      lipid peroxidation and its adduction to neuronal proteins has been demonstrated
      in diseased brain regions from patients with Alzheimer's disease. Mitochondrial
      abnormalities are implicated in several neurodegenerative disorders, and
      mitochondria are targets of alkenal adduction in vivo. We examined the effects of
      acrolein upon multiple endpoints associated with the mitochondrial involvement in
      neurodegenerative disease. Acrolein inhibited state 3 respiration with an IC(50)
      of approx. 0.4 micromol/mg protein; however, there was no reduction in activity
      of complexes I-V. This inhibition was prevented by glutathione and N
      acetylcysteine. Acrolein did not alter mitochondrial calcium transporter activity
      or induce cytochrome c release. These studies indicate that acrolein is a potent
      inhibitor of brain mitochondrial respiration.

PMID- 11342004
TI  - The effect of Pb(2+) on the structure and hydroxyapatite binding properties of
      osteocalcin.
AB  - Lead toxicity is a major environmental health problem in the United States. Bone
      is the major reservoir for body lead. Although lead has been shown to impair bone
      metabolism in animals and at the cellular level, the effect of Pb(2+) at the
      molecular level is largely unknown. We have used circular dichroism (CD), and a
      hydroxyapatite binding assay to investigate the effect of Pb(2+) on the structure
      and mineral binding properties of osteocalcin, a noncollagenous bone protein. The
      CD data indicate Pb(2+) induces a similar structure in osteocalcin as Ca(2+) but
      at 2 orders of magnitude lower concentration. These results were explained by the
      more than 4 orders of magnitude tighter binding of Pb(2+) to osteocalcin
      (K(d)=0.085 microM) than Ca(2+) (K(d)=1.25 mM). The hydroxyapatite binding assays
      show that Pb(2+) causes an increased adsorption to hydroxyapatite, similar to
      Ca(2+), but at 2-3 orders of magnitude lower concentration. Low Pb(2+) levels (1
      microM) in addition to physiological Ca(2+) levels (1 mM) caused a significant
      (40%) increase in the amount of mineral bound osteocalcin as compared to 1 mM
      Ca(2+) alone. These results suggest a molecular mechanism of Pb(2+) toxicity
      where low Pb(2+) levels can inappropriately perturb Ca(2+) regulated processes.
      In-vivo, the increased mineral bound osteocalcin could play a role in the
      observed low bone formation rates and decreased bone density observed in Pb(2+)
      intoxicated animals.

PMID- 11342005
TI  - The measured level of prion infectivity varies in a predictable way according to
      the aggregation state of the infectious agent.
AB  - Transmissible spongiform encephalopathies are believed to be caused by an
      infectious form of the prion protein, designated PrP(Sc). The concentration of
      PrP(Sc) is often poorly correlated to the level of infectivity. Infectivity can
      be measured in two ways, namely endpoint titration and the incubation time assay,
      but patterns of infectivity vary depending on which method is used. These
      discrepancies can be explained by variation in the aggregation state of PrP(Sc).
      Both methods of measuring infectivity are modelled mathematically, and the
      theoretical results are in agreement with published data. It was found to be
      theoretically impossible to characterise prion infectivity by a multiple of a
      single quantity representing 'one prion', no matter how it is measured.
      Infectivity is instead characterised by both the number and sizes of the PrP(Sc)
      aggregates. Apparent discrepancies arise when these complexities are reduced to a
      single number.

PMID- 11342006
TI  - Insulin can enhance GLUT4 gene expression in 3T3-F442A cells and this effect is
      mimicked by vanadate but counteracted by cAMP and high glucose--potential
      implications for insulin resistance.
AB  - It is well-established that high levels of cAMP or glucose can produce insulin
      resistance. The aim of this study was to characterize the interaction between
      these agents and insulin with respect to adipose tissue/muscle glucose
      transporter isoform (glucose transporter 4, GLUT4) gene regulation in cultured
      3T3-F442A adipocytes and to further elucidate the GLUT4-related mechanisms in
      insulin resistance. Insulin (10(4) microU/ml) treatment for 16 h clearly
      increased GLUT4 mRNA level in cells cultured in medium containing 5.6 mM glucose
      but not in cells cultured in medium with high glucose (25 mM). 8-Bromo-cAMP (1 or
      4 mM) or N(6)-monobutyryl cAMP, a hydrolyzable and a non-hydrolyzable cAMP
      analog, respectively, markedly decreased the GLUT4 mRNA level irrespective of
      glucose concentrations. In addition, these cAMP analogs also inhibited the
      upregulating effect of insulin on GLUT4 mRNA level. Interestingly, the tyrosine
      phosphatase inhibitor vanadate (1-50 microM) clearly increased GLUT4 mRNA level
      in a time- and concentration-dependent manner. Furthermore, cAMP-induced
      inhibition of the insulin effect was also prevented by vanadate. In parallel to
      the effects on GLUT4 gene expression, both insulin, vanadate and cAMP produced
      similar changes in cellular GLUT4 protein content and cAMP impaired the effect of
      insulin to stimulate (14)C-deoxyglucose uptake. In contrast, insulin, vanadate or
      cAMP did not alter insulin receptor (IR) mRNA or the cellular content of IR
      protein. IN CONCLUSION: (1) Both insulin and vanadate elicit a stimulating effect
      on GLUT4 gene expression in 3T3-F442A cells, but a prerequisite is that the
      surrounding glucose concentration is low. (2) Cyclic AMP impairs the insulin
      effect on GLUT4 gene expression, but this is prevented by vanadate, probably by
      enhancing the tyrosine phosphorylation of signalling peptides and/or
      transcription factors. (3) IR gene and protein expression is not altered by
      insulin, vanadate or cAMP in this cell type. (4) The changes in GLUT4 gene
      expression produced by cAMP or vanadate are accompanied by similar alterations in
      GLUT4 protein expression and glucose uptake, suggesting a role of GLUT4 gene
      expression for the long-term regulation of cellular insulin action on glucose
      transport.

PMID- 11342007
TI  - Evaluation of oxidative stress during apoptosis and necrosis caused by carbon
      tetrachloride in rat liver.
AB  - After 12, 18, and 24 h of oral administration of carbon tetrachloride (as a 1:1
      mixture with mineral oil: 4 ml/kg body weight) to rats, the activity of caspase-3
      like protease in the liver increased significantly compared to that in the
      control group that was given mineral oil (4 ml/kg). In plasma, the activity of
      caspase-3 was barely detectable in the control rat, but increased significantly
      24 h after drug administration along with a dramatic increase in glutamate
      oxaloacetate transaminase. These results indicate that carbon tetrachloride
      causes apoptosis in the liver by activating caspase-3, which is released to
      plasma by secondary necrosis. After 18 and 24 h of carbon tetrachloride
      administration, the liver concentration of hydrophilic vitamin C was decreased
      significantly, while that of hydrophobic vitamin E was not affected. The plasma
      concentration of vitamins C and E was not influenced significantly. These results
      suggest that carbon tetrachloride induces oxidative stress mainly in the aqueous
      phase of the liver cell.

PMID- 11342008
TI  - Differentially expressed DNA sequences following recovery from unilateral
      testicular torsion in rat.
AB  - The molecular response during recovery from torsion-induced stress in the testis
      is diverse with a variety of mechanisms. In this study, using unilateral
      testicular torsion in rat as a model, we used subtractive hybridisation to
      identify differentially expressed DNA sequences in the torsioned and control
      testes. Three genes were identified as being down regulated in the torsioned
      testis compared with controls: Control Testis genes 1, 2 and 3 (CT1, CT2 and
      CT3). Two genes were up regulated in the torsioned testes: Torsioned Testes genes
      1 and 2 (TT1 and TT2). Differential expression was confirmed by Reverse Northern
      blot analysis. An homology search revealed that CT1 had 88% homology with rat
      metallothionein cDNA; CT2 had 81% homology with rat cell surface antigen in MHC
      class I, but no homology could be found for CT3. TT1 had 92% identity with rat
      Rieske iron-sulphur protein mRNA whereas TT2 had 73% identity with a human clone
      of unknown function (RP 11-252D22). These results indicate that changes in gene
      expression occur following torsion induced stress, and that identification of
      differentially expressed genes may provide insights into the mechanisms of
      cellular tissue damage in this model.

PMID- 11342009
TI  - Lanthanide ions induce hydrolysis of hemoglobin-bound 2,3-diphosphoglycerate (2,3
      DPG), conformational changes of globin and bidirectional changes of 2,3-DPG
      hemoglobin's oxygen affinity.
AB  - The changes in structure and function of 2,3-diphosphoglycerate-hemoglobin (2,3
      DPG-Hb) induced by Ln(3+) binding were studied by spectroscopic methods. The
      binding of lanthanide cations to 2,3-DPG is prior to that to Hb. Ln(3+) binding
      causes the hydrolysis of either one from the two phosphomonoester bonds in 2,3
      DPG non-specifically. The results using the ultrafiltration method indicate that
      Ln(3+) binding sites for Hb can be classified into three categories: i.e.
      positive cooperative sites (N(I)), non-cooperative strong sites (N(S)) and non
      cooperative weak sites (N(W)) with binding constants in decreasing order:
      K(I)>K(S)>K(W). The total number of binding sites amounts to about 65 per Hb
      tetramer. Information on reaction kinetics was obtained from the change of
      intrinsic fluorescence in Hb monitored by stopped-flow fluorometry. Fluctuation
      of fluorescence dependent on Ln(3+) concentration and temperature was observed
      and can be attributed to the successive conformational changes induced by Ln(3+)
      binding. The results also reveal the bidirectional changes of the oxygen affinity
      of Hb in the dependence on Ln(3+) concentration. At the range of [Ln(3+)]/[Hb]<2,
      the marked increase of oxygen affinity (P(50) decrease) with the Ln(3+)
      concentration can be attributed to the hydrolysis of 2,3-DPG, while the slight
      rebound of oxygen affinity in higher Ln(3+) concentration can be interpreted by
      the transition to the T-state of the Hb tetramer induced by Ln(3+) binding. This
      was indicated by the changes in secondary structure characterized by the decrease
      of alpha-helix content.

PMID- 11342011
TI  - Answer to the previous case of the month.

PMID- 11342010
TI  - Case of the month.
AB  - Each month, we will present a challenging Case of the Month for Green Journal
      readers, who must use their clinical acumen to arrive at the correct answer. We
      will also post the case each month on the Journal's web site
      (http://www.elsevier.com/ajmselect). Several possible answers may be consistent
      with the case presentation; use your best judgment. Please send your answer (one
      per respondent) to The Green Journal at editors@amjmed.org or via FAX to (415)
      447-2799. Indicate the case to which you are responding and include your complete
      address. The correct answer will appear in the next issue of the Journal. The
      first five persons who submit correct answers will receive a free one-year
      subscription to the Journal. Because of the volume of answers we receive, neither
      correct nor incorrect answers can be individually acknowledged. Colleagues of
      Drs. Green, Nallamothu, and Shea are not eligible for this month's case. If you
      would like to contribute a case, please submit a brief synopsis (<250 words) to
      the editorial office.

PMID- 11342012
TI  - In this issue ellipsis.

PMID- 11342013
TI  - Commentary.

PMID- 11342014
TI  - Commentary.

PMID- 11342015
TI  - Commentary.

PMID- 11342016
TI  - Commentary.

PMID- 11342017
TI  - Commentary.

PMID- 11342019
TI  - Commentary.

PMID- 11342018
TI  - Commentary.

PMID- 11342020
TI  - Commentary.

PMID- 11342025
TI  - Redox state dependence of rotamer distributions in tyrosine and neutral tyrosyl
      radical.
AB  - Redox state-dependent changes in the relative orientation of the phenol side
      chain and the peptide group in model tyrosine have been characterized using
      specific 2H isotopic labelling and X-band electron paramagnetic resonance (EPR)
      spectroscopy. Tyrosyl radicals were generated by UV photolysis of tyrosine
      trapped in rigid polycrystalline basic-aqueous medium at T < or = 170 K. Ring
      2H(4) and beta-2H(2) substitutions on tyrosine were used to enhance the lineshape
      contributions from beta-hydrogen or ring-hydrogen hyperfine interactions,
      respectively. The EPR lineshape at 120 K of the trapped ring-2H(4)-tyrosyl
      radical is altered dramatically after annealing at 235 K. In contrast, the
      lineshape of the beta-2H(2)-tyrosyl radical is impervious to annealing. The
      effect of annealing on the lineshape therefore arises from a change in the
      isotropic hyperfine coupling between unpaired pi-electron spin density at the
      ring carbon atom C(1) and the beta-hydrogen nuclei, which is caused by rotational
      relaxation of the ring and peptide group about the C(1)-C(beta) bond. EPR
      simulations indicate angular distributions of the peptide group (R-) of 0 degrees
      < or = theta(R) < or = 30 degrees and 0 degrees < or = theta(R)< or = 18 degrees
      in the rigid and relaxed radical states, respectively. Redox-induced changes in
      the C(1)-C(beta) rotamer distribution must be accounted for in assessments of
      stable amino acid side chain equilibrium structures, and may influence catalytic
      tyrosyl radical/tyrosine function in enzymes.

PMID- 11342026
TI  - Inhibition kinetics of green crab (Scylla serrata) alkaline phosphatase by zinc
      ions: a new type of complexing inhibition.
AB  - The Tsou method was used to study the kinetic course of inactivation of green
      crab alkaline phosphatase by zinc ions. The results show that the enzyme was
      inactivated by a complexing scheme which has not been previously identified. The
      enzyme first reversibly and quickly binds Zn(2+) and then undergoes a slow
      reversible course to inactivation and slow conformational change. The
      inactivation reaction is a single molecule reaction and the apparent inactivation
      rate constant is for a saturated reaction being independent of Zn(2+)
      concentration if the concentration is sufficiently high. The microscopic rate
      constants of inactivation and the association constant were determined from the
      measurements.

PMID- 11342027
TI  - Ribonuclease Rs from Rhizopus stolonifer: lowering of optimum temperature in the
      presence of urea.
AB  - RNase Rs showed an approx. 2-fold increase in its activity when incubated in the
      presence of 2 M urea at 37 degrees C. The increase in its activity, in the
      presence of urea, was comparable to the activity at its optimum temperature, i.e.
      45 degrees C. Compared to the native enzyme at 37 degrees C, the K(m) and V(max)
      of RNase Rs at 45 degrees C and in the presence of 2 M urea at 37 degrees C
      showed an increase while k(cat)/K(m) decreased. Arrhenius plots in the presence
      and absence of urea showed a decrease in the activation energy in the presence of
      urea. Though there was no change in the secondary structure of the protein in the
      presence of urea, minor changes were observed in the tertiary structure. Hence,
      the increase in the activity of RNase Rs, in the presence of 2 M urea at 37
      degrees C, is due to the lowering of the activation energy as a result of changes
      in the microenvironment of the active site.

PMID- 11342028
TI  - A model of activation of the protein tyrosine phosphatase SHP-2 by the human
      leptin receptor.
AB  - Signalling through the leptin receptor has been shown to activate the SH2 domain
      containing tyrosine phosphatase SHP-2 through tyrosine phosphorylation. The human
      leptin receptor contains five tyrosine residues in the cytoplasmic domain that
      may become phosphorylated. We show here using BIAcore studies, wherein binding of
      peptides to SHP-2 was detected, that peptides corresponding to sequences
      containing phosphotyrosines 974 and 986 (LR974P and LR986P, respectively) from
      the leptin receptor cytoplasmic domain were the only two peptides that bound to
      the enzyme. Binding of LR974P to SHP-2 was inhibited in a dose-dependent fashion
      by orthovanadate, whereas binding of LY986P was not, indicating that the enzyme
      binds to these peptides through different sites. Only the leptin receptor-derived
      peptide corresponding to tyrosine 974 was dephosphorylated by recombinant
      purified SHP-2. Time courses of the reaction were complex, and fitted a two
      exponent rate equation. Preincubation of SHP-2 with LR986P markedly activated the
      enzyme at early time points and time courses of the activated enzyme fitted a
      single exponential first order rate equation. We propose that LR974P binds to the
      active site of SHP-2, whereas LR986P may bind to the N- and C-terminal SH2
      domains of SHP-2, thus activating the phosphatase activity. These data support a
      model in which SHP-2 binds to phosphotyrosine 986 in the activated leptin
      receptor and is activated to dephosphorylate phosphotyrosine 974, downregulating
      signalling events emanating from SH2 domain-containing proteins that bind here.

PMID- 11342029
TI  - Purification and properties of three new phospholipase A2 isoenzymes from
      Micropechis ikaheka venom.
AB  - Three new phospholipase A2 (PLA2) isoenzymes were purified from the Micropechis
      ikaheka venom by successive chromatographies. The homogeneity of them was
      accessed by capillary zone electrophoresis and mass spectrometry. Their N
      terminal sequences showed high identity (94, 88 and 90, respectively) with MiPLA
      1, a group IB PLA2 also from this venom. In addition, strong immuno-cross
      reaction with anti-MiPLA-1 serum was observed. These results suggested that three
      newly purified PLA2 belonged to group IB. Beside enzymatic activity, they induced
      various pharmacological effects, including myotoxic, anticoagulant effects and
      insulin secretion stimulating effects. Our results indicated that enzymatic
      activity is essential for their myotoxic and anticoagulant effects. On the other
      hand, no direct correlation between their insulin secretion stimulating effect
      and enzymatic activity was observed, suggesting that they may stimulate insulin
      secretion through a non-enzymatic mechanism.

PMID- 11342030
TI  - Amino acid residues involved in substrate binding and catalysis in an insect
      digestive beta-glycosidase.
AB  - A beta-glycosidase (M(r) 50000) from Spodoptera frugiperda larval midgut was
      purified, cloned and sequenced. It is active on aryl and alkyl beta-glucosides
      and cellodextrins that are all hydrolyzed at the same active site, as inferred
      from experiments of competition between substrates. Enzyme activity is dependent
      on two ionizable groups (pK(a1)=4.9 and pK(a2)=7.5). Effect of pH on carbodiimide
      inactivation indicates that the pK(a) 7.5 group is a carboxyl. k(cat) and K(m)
      values were obtained for different p-nitrophenyl beta-glycosides and K(i) values
      were determined for a range of alkyl beta-glucosides and cellodextrins, revealing
      that the aglycone site has three subsites. Binding data, sequence alignments and
      literature beta-glycosidase 3D data supported the following conclusions: (1) the
      groups involved in catalysis were E(187) (proton donor) and E(399) (nucleophile);
      (2) the glycone moiety is stabilized in the transition state by a hydrophobic
      region around the C-6 hydroxyl and by hydrogen bonds with the other equatorial
      hydroxyls; (3) the aglycone site is a cleft made up of hydrophobic amino acids
      with a polar amino acid only at its first (+1) subsite.

PMID- 11342031
TI  - Cloning and biochemical characterization of Co(2+)-activated bromoperoxidase
      esterase (perhydrolase) from Pseudomonas putida IF-3 strain.
AB  - The gene encoding Co(2+)-activated bromoperoxidase (BPO)-esterase (EST),
      catalyzing the organic acid-assisted bromination of some organic compounds with
      H2O2 and Br(-) and quite specific hydrolysis of (R)-acetylthioisobutyric acid
      methyl ester, was cloned from the chromosomal DNA of the Pseudomonas putida IF-3
      strain. The bpo-est gene comprises 831 bp and encoded a protein of 30181 Da. The
      enzyme was expressed at a high level in Escherichia coli and purified to
      homogeneity by ammonium sulfate fractionation and two-step column
      chromatographies. The recombinant enzyme required acetic acid, propionic acid,
      isobutyric acid or n-butyric acid in addition to H2O2 and Br(-) for the
      brominating reaction and was activated by Co(2+) ions. It catalyzed the
      bromination of styrene and indene to give the corresponding racemic bromohydrin.
      Although the enzyme did not release free peracetic acid in the reaction mixture,
      chemical reaction with peracetic acid could well explain such enzymatic reactions
      via a peracetic acid intermediate. The results indicated that the enzyme was a
      novel Co(2+)-activated organic acid-dependent BPO (perhydrolase)-EST, belonging
      to the non-metal haloperoxidase-hydrolase family.

PMID- 11342032
TI  - Inhibitors of dihydrodipicolinate reductase, a key enzyme of the diaminopimelate
      pathway of Mycobacterium tuberculosis.
AB  - Tuberculosis (TB) remains a leading cause of infectious disease in the world
      today and therapies developed over the last forty years are becoming increasingly
      ineffective against resistant strains of Mycobacterium tuberculosis. In an effort
      to explore new mechanisms for drug development, we have investigated the enzymes
      of the diaminopimelate biosynthetic pathway as potential targets. Specifically,
      dihydrodipicolinate reductase, the essential gene product of dapB, was screened
      for novel inhibitors. Inhibitors were identified both by a molecular modeling
      approach which utilized the available crystal structure of the enzyme with an
      inhibitor bound at the active site as well as by more conventional screening
      strategies. The resulting compounds contain a number of structural motifs and
      were all found to be competitive with respect to the DHDP substrate. The K(i)
      values for the inhibitors range from 10 to 90 microM. The molecular modeling
      approach was very effective in identifying novel inhibitors of the enzyme. These
      compounds were obtained at a higher frequency based on the number of compounds
      analyzed than those inhibitors discovered via conventional screening. However,
      conventional screening proved beneficial in identifying compounds with greater
      structural diversity.

PMID- 11342033
TI  - Enhancement of chymotrypsin-inhibitor/substrate interactions by 3 M NaCl.
AB  - A series of 16 bovine pancreatic trypsin inhibitor variants mutated at the P(1)
      position of the binding loop and seven tetrapeptide p-nitroanilide (pNa)
      substrates of the general formula: suc-Ala-Ala-Pro-Aaa-pNa (where Aaa denotes
      either: Phe, Arg, Lys, Leu, Met, Nva, Nle) were used to investigate the influence
      of high salt concentration on the activity of bovine chymotrypsin. The increase
      of the association constant (K(a)) and the specificity index (k(cat)/K(m)) in the
      presence of 3 M NaCl highly depends on the chemical nature of the residue at the
      P(1) position. The highest increase was observed for inhibitors/substrates
      containing the basic side chains at this site. Surprisingly, for the remaining 13
      residues the observed salt effect is not correlated with any side chain
      properties. In particular, there is a lack of correlation between the accessible
      non-polar surface area and the magnitude of the salt effect. It suggests that
      salt-induced increase of the K(a) and k(cat)/K(m) values is not caused by the
      enhancement of the hydrophobic interactions in chymotrypsin-inhibitor/substrate
      complex. Moreover, the increase of the K(a) and k(cat)/K(m) values occurs only in
      the presence of Na(+) ions, while K(+) and Li(+) ions do not change the activity
      of chymotrypsin. Additionally, the activities of two other proteinases: bovine
      trypsin and Streptomyces griseus proteinase B were tested in the presence of 3 M
      NaCl using their specific substrates. The activity of both enzymes was almost not
      affected by the presence of high NaCl concentration.

PMID- 11342034
TI  - Is salivary histatin 5 a metallopeptide?
AB  - Histatins are small histidine-rich salivary polypeptides which exhibit
      antimicrobial activity against Candida albicans. This antimicrobial activity has
      been ascribed in part to a high content of basic amino acids. However, unlike
      most other antimicrobial proteins histatins have a high content of histidine,
      tyrosine and acidic amino acids known to participate in metal ion coordination.
      This study was conducted to test whether histatin 5 could bind zinc and copper
      which are metals present in salivary secretions and whole saliva. Physical
      binding parameters and spectral properties of zinc- and copper-histatin complexes
      were investigated in order to obtain direct evidence of these interactions. A
      spectrophotometric competition assay using the metallochromic indicator murexide
      showed that histatin 5 dissociates metal indicator complexes containing zinc or
      copper ions. Absorption spectra of histatin 5 at increasing copper chloride
      concentrations resulted in higher absorbance in the 230-280 nm wavelength range
      and this spectral change was saturated at a peptide:metal molar ratio of approx.
      1:1. A corresponding band was observed in the visible range of the spectrum with
      a maximum and molar extinction coefficient corresponding to that of copper
      binding to an ATCUN motif. Quantitative assessment of zinc and copper binding to
      histatin 5 using isothermal titration calorimetry revealed at least one high
      affinity site for each metal, with binding constants of 1.2x10(5) and 2.6x10(7)
      M(-1), respectively. These results indicate that histatin 5 exhibits
      metallopeptide-like properties. The precise biological significance of this has
      not yet been established but histatins may contribute significantly to salivary
      metal binding capacity.

PMID- 11342035
TI  - Differences in the pathways for unfolding and hydrogen exchange among mutants of
      Escherichia coli alkaline phosphatase.
AB  - Our initial studies of hydrogen-deuterium (H-D) exchange of tryptophan 109 in
      Escherichia coli alkaline phosphatase (AP) suggested that significant local
      unfolding of the protein might occur to allow for the exchange reaction, which is
      very slow at room temperature (Fischer et al., Biochemistry 39 (2000) 1455-1461).
      In order to investigate whether the partial unfolding and/or 'breathing' motions
      leading to H-D exchange were part of the unfolding pathway of the protein we
      prepared a series of mutants, designed to produce cavities around the exchanging
      residue, and compared their rates of H-D exchange to their lability (rate of
      inactivation) in guanidine hydrochloride (Gd:HCl). The complex unfolding kinetics
      of the mutants in the presence of Gd:HCl showed several components with rates
      that differed substantially among these proteins, but none of the rates of
      denaturation induced with Gd:HCl was consistently correlated with the H-D
      exchange rates. We conclude that the partial opening of the AP structure during
      the H-D exchange of tryptophan 109, although very slow, is not a rate determining
      step in the unfolding of this protein.

PMID- 11342036
TI  - Isolation and characterization of an alpha-macroglobulin from the gastropod
      mollusc Helix pomatia with tetrameric structure and preserved activity after
      methylamine treatment.
AB  - A proteinase inhibitor with M(r) 697000 and 20.3% (w/w) carbohydrate was isolated
      from the haemolymph of the snail Helix pomatia and characterized. It was shown to
      have a tetrameric structure with subunits disulphide linked by two. It inhibited
      the activity of several types of proteinases against large substrates but not
      that of trypsin against N-alpha-benzoyl-DL-arginine-4-nitroanilide. This
      indicated a nonspecific and steric hindrance mode of inhibition. The ratio of
      trypsin molecules inactivated per inhibitor amounted to 1.5. This interaction led
      to a cleavage of the subunits into two equal fragments and to a slow to fast
      conformational change of the whole molecules. Experiments with 125I-labelled
      trypsin indicated that the proteinase had become covalently linked to one of the
      fragments. Heating of the inhibitor led to autolytic cleavage products but not
      when methylamine treated. Thiol titration after trypsin or methylamine treatment
      indicated the presence of one thiol ester bond per subunit. These facts are all
      indicative of an alpha-macroglobulin type of inhibitor. However, unlike for most
      of them the methylamine treatment did not induce a conformational change nor
      suppress its proteinase inhibitory activity. Moreover, invertebrate alpha
      macroglobulins are mostly dimeric in structure but tetramers likewise do occur in
      Biomphalaria glabrata.

PMID- 11342037
TI  - Rational evolution of a medium chain-specific cytochrome P-450 BM-3 variant.
AB  - The single mutant F87A of cytochrome P-450 BM-3 from Bacillus megaterium was
      engineered by rational evolution to achieve improved hydroxylation activity for
      medium chain length substrates (C8-C10). Rational evolution combines rational
      design and directed evolution to overcome the drawbacks of these methods when
      applied individually. Based on the X-ray structure of the enzyme, eight mutation
      sites (P25, V26, R47, Y51, S72, A74, L188, and M354) were identified by modeling.
      Sublibraries created by site-specific randomization mutagenesis of each single
      site were screened using a spectroscopic assay based on omega-p
      nitrophenoxycarboxylic acids (pNCA). The mutants showing activity for shorter
      chain length substrates were combined, and these combi-libraries were screened
      again for mutants with even better catalytic properties. Using this approach, a P
      450 BM-3 variant with five mutations (V26T, R47F, A74G, L188K, and F87A) that
      efficiently hydrolyzes 8-pNCA was obtained. The catalytic efficiency of this
      mutant towards omega-p-nitrophenoxydecanoic acid (10-pNCA) and omega-p
      nitrophenoxydodecanoic acid (12-pNCA) is comparable to that of the wild-type P
      450 BM-3.

PMID- 11342038
TI  - Partially folded states of the cytolytic protein sticholysin II.
AB  - Sticholysin II (Stn II) is a cytolytic protein produced by the sea anemone
      Stichodactyla helianthus, its effect being related to pore formation. The
      conformation of the protein and its temperature-induced transitions, in the 1.5
      12.0 pH range and in the 0-0.5 M NaCl concentration interval, have been studied
      by circular dichroism and fluorescence spectroscopy. At temperature < 35 degrees
      C, the protein maintains the same, high beta-structure content, folded
      conformation in the 1.5-11.0 pH range and ionic strength up to 0.5 M. In the 1.5
      3.5 pH range and ionic strength > or = 0.1 M, Stn II shows a thermal transition,
      resulting in a partially folded state characterized by: (i) a native-like content
      of regular secondary structure, as detected by far-UV CD; (ii) a largely
      disordered tertiary structure, as detected by near-UV CD, with partially exposed
      tryptophan residues according to their fluorescence emission; and (iii) ability
      to bind the hydrophobic probe 2-anilinonaphthalene-6-sulfonic acid. In the pH
      range 4.0-10.5, thermally-induced protein aggregation occurs. The obtained
      results demonstrate the existence of partially folded state of Stn II, which may
      contribute to the pore formation ability of this cytolysin.

PMID- 11342039
TI  - Substrate and cofactor binding to fluorescently labeled cytoplasmic malate
      dehydrogenase.
AB  - Cytoplasmic malate dehydrogenase (cMDH) is a key enzyme in several metabolic
      pathways. Though its activity has been examined extensively, there are lingering
      mechanistic uncertainties involving substrate and cofactor binding. To more
      completely understand this enzyme's interactions with cofactor and substrate
      ligands, a fluorescent reporter group was introduced into the enzyme's structure.
      This was accomplished by selective modification of Cys 110. The reaction placed
      an aminonaphthaline sulfonic acid group near the enzyme's active site. Substrate,
      inhibitor, and NAD binding activities were characterized using changes in this
      label's fluorescence. Results demonstrated that both substrate and cofactor
      molecules bound to the enzyme in the absence of their companion ligands. This is
      in contrast to strictly ordered cofactor then substrate binding as has been
      suggested by kinetic analyses of closely related enzymes. Binding results also
      indicated that the cofactor, NAD, bound to cMDH in a negatively cooperative
      manner, but substrates and the inhibitor, hydroxymalonate, bound non
      cooperatively. Multiple substrate binding modes were identified and interactions
      between substrate and cofactor binding were found.

PMID- 11342040
TI  - Isolation of chymase complexed with physiological inhibitor similar to secretory
      leukocyte protease inhibitor (SLPI) from hamster cheek pouch tissues.
AB  - A low molecular weight protein complexed with chymase was isolated from hamster
      cheek pouch tissues. This protein had an apparent molecular mass of about 10 kDa
      on SDS-PAGE and the N-terminal sequence showed some homology to secretory
      leukocyte protease inhibitor (SLPI), which is known as the predominant inhibitor
      of neutrophil elastase and cathepsin G. Remarkably enhanced inhibition of chymase
      activity was achieved in the presence of heparin, indicating that the functional
      property was also similar to SLPI. These findings suggest that this SLPI-like
      protein is a candidate for a physiological inhibitor of chymase.

PMID- 11342041
TI  - Solution structure of micelle-bound H5 peptide (427-452): a primary structure
      corresponding to the pore forming region of the voltage dependent potassium
      channel.
AB  - A 26-mer peptide with the sequence of the pore forming region (residues 427-452)
      of the Shaker K(+) channel (H5 region) was chemically synthesized. Analyses by CD
      and two-dimensional 1H NMR spectroscopy were used to investigate the structure of
      the peptide bound to SDS micelles in solution, which are commonly used in
      biophysical studies. The tertiary structure of the peptide as a monomer was
      composed of an alpha-helix (431-438), a turn (439-442), and random coils (427
      430, 443-452), and was very similar to that of the pore forming region of the
      native K(+) channel from Streptomyces lividans determined by X-ray analysis. This
      result suggests that even an isolated peptide forms a native-like conformation
      for residues from 431 to 442, depending on its intrinsic amino acid sequence and
      the surrounding environment.

PMID- 11342042
TI  - Nucleotide binding to the chaperonin GroEL: non-cooperative binding of ATP
      analogs and ADP, and cooperative effect of ATP.
AB  - Chaperonin-assisted protein folding proceeds through cycles of ATP binding and
      hydrolysis by GroEL, which undergoes a large structural change by the ATP binding
      or hydrolysis. One of the main concerns of GroEL is the mechanism of the
      productive and cooperative structural change of GroEL induced by the nucleotide.
      We studied the cooperative nature of GroEL by nucleotide titration using
      isothermal titration calorimetry and fluorescence spectroscopy. Our results
      indicated that the binding of ADP and ATP analogs to a single ring mutant (SR1),
      as well as that to GroEL, was non-cooperative. Only ATP induces an apparently
      cooperative conformational change in both proteins. Furthermore, the fluorescence
      changes of pyrene-labeled GroEL indicated that GroEL has two kinds of nucleotide
      binding sites. The fluorescence titration result fits well with a model in which
      two kinds of binding sites are both non-cooperative and independent of each
      other. These results suggest that the binding and hydrolysis of ATP may be
      necessary for the cooperative transition of GroEL.

PMID- 11342043
TI  - Thermostabilization of a chimeric enzyme by residue substitutions: four amino
      acid residues in loop regions are responsible for the thermostability of Thermus
      thermophilus isopropylmalate dehydrogenase.
AB  - A chimeric 3-isopropylmalate dehydrogenase, named 2T2M6T, made of parts from an
      extreme thermophile, Thermus thermophilus, and a mesophile, Bacillus subtilis,
      was found to be considerably more labile than the T. thermophilus wild-type
      isopropylmalate dehydrogenase. In order to identify the molecular basis of the
      thermal stability of the T. thermophilus isopropylmalate dehydrogenase, 11 amino
      acid residues in the mesophilic portion of the chimera were substituted by the
      corresponding residues of the T. thermophilus enzyme, and the effects of the side
      chain substitutions were analyzed by comparing the reaction rate of irreversible
      heat denaturation and catalytic parameters of the mutant chimeras with those of
      the original chimera, 2T2M6T. Four single-site mutants were successfully
      stabilized without any loss of the catalytic function. All these four sites are
      located in loop regions of the enzyme. Our results strongly suggest the
      importance of these loop structures to the extreme stability of the T.
      thermophilus isopropylmalate dehydrogenase.

PMID- 11342044
TI  - Changes in the kinetic parameters of hepatic gamma-glutamyltransferase from
      streptozotocin-induced diabetic rats.
AB  - Previous research has shown that the enzymatic activity of hepatic gamma
      glutamyltransferase was increased in streptozotocin-induced diabetic rats with no
      increase in the expression of the protein. The current work has characterized the
      differences in the kinetic properties of hepatic gamma-glutamyltransferase from
      diabetic versus control rats. Hepatic gamma-glutamyltransferase was purified from
      control male and female rats and from rats made diabetic 30 days previously with
      streptozotocin. The maximal velocity and the Michaelis constant were determined
      for the purified enzyme with two separate donors (L-gamma-glutamyl-p-nitroanilide
      or L-gamma-glutamyl-(7-amido-4-methylcoumarin)) in the presence of one of eight
      acceptors (L-alanine-glycine, L-glycine-glycine, L-methionine, L-glutamate, L
      alanine, L-glutamine, L-phenylalanine or L-aspartate). With both donors, hepatic
      gamma-glutamyltransferase from diabetic rats had a consistently higher kinetic
      efficiency than gamma-glutamyltransferase from controls. The kinetic efficiency
      percent increase of diabetic over control gamma-glutamyltransferase when averaged
      across all acceptors was higher in males than in females. With L-gamma-glutamyl-p
      nitroanilide, the kinetic efficiency increase of diabetic over control gamma
      glutamyltransferase was higher with poor acceptors than with highly efficient
      acceptors. These data indicate that there are differences in the physical
      properties of hepatic gamma-glutamyltransferase from diabetic versus control rats
      and from female versus male rats.

PMID- 11342045
TI  - Protease C2, a cysteine endopeptidase involved in the continuing mobilization of
      soybean beta-conglycinin seed proteins.
AB  - The protease that degrades the beta subunit of the soybean (Glycine max (L.)
      Merrill) storage protein beta-conglycinin was purified from the cotyledons of
      seedlings grown for 12 days. The enzyme was named protease C2 because it is the
      second enzyme to cleave the beta-conglycinin storage protein, the first (protease
      C1) being one that degrades only the alpha' and alpha subunits of the storage
      protein to products similar in size and sequence to the remaining intact beta
      subunit. Protease C2 activity is not evident in vivo until 4 days after
      imbibition of the seed. The 31 kDa enzyme is a cysteine protease with a pH
      optimum with beta-conglycinin as substrate of 5.5. The action of protease C2 on
      native beta-conglycinin produces a set of large fragments (52-46 kDa in size) and
      small fragments (29-25 kDa). This is consistent with cleavage of all beta
      conglycinin subunits at the region linking their N- and C-domains. Protease C2
      also cleaves phaseolin, the Phaseolus vulgaris vicilin homologous to beta
      conglycinin, to fragments in the 25-28 kDa range. N-Terminal sequences of
      isolated beta-conglycinin and phaseolin products show that protease C2 cleaves at
      a bond within a very mobile surface loop connecting the two compact structural
      domains of each subunit. The protease C2 cleavage specificity appears to be
      dictated by the substrate's three-dimensional structure rather than a specificity
      for a particular amino acid or sequence.

PMID- 11342046
TI  - Slow inhibition of almond beta-glucosidase by azasugars: determination of
      activation energies for slow binding.
AB  - The thermodynamic and activation energies of the slow inhibition of almond beta
      glucosidase with a series of azasugars were determined. The inhibitors studied
      were isofagomine ((3R,4R,5R)-3,4-dihydroxy-5-hydroxymethylpiperidine, 1),
      isogalactofagomine ((3R,4S,5R)-3,4-dihydroxy-5-hydroxymethylpiperidine, 2), (-)-1
      azafagomine ((3R,4R,5R)-4,5-dihydroxy-3-hydroxymethylhexahydropyridazine, 3), 3
      amino-3-deoxy-1-azafagomine (4) and 1-deoxynojirimycin (5). It was found that the
      binding of 1 to the enzyme has an activation enthalpy of 56.1 kJ/mol and an
      activation entropy of 25.8 J/molK. The dissociation of the enzyme-1 complex had
      an activation enthalpy of -2.5 kJ/mol and an activation entropy of -297 J/molK.
      It is suggested that the activation enthalpy of association is due to the
      breaking of bonds to water, while the large negative activation entropy of
      dissociation is due at least in part to the resolvation of the enzyme with water
      molecules. For the association of 1 DeltaH(0) is 58.6 kJ/mol and DeltaS(0) is
      323.8 J/molK. Inhibitor 3 has an activation enthalpy of 39.3 kJ/mol and an
      activation entropy of -17.9 J/molK for binding to the enzyme, and an activation
      enthalpy of 40.8 kJ/mol and an activation entropy of -141.0 J/molK for
      dissociation of the enzyme-inhibitor complex. For the association of 3 DeltaH(0)
      is -1.5 kJ/mol and DeltaS(0) is 123.1 J/molK. Inhibitor 5 is not a slow
      inhibitor, but its DeltaH(0) and DeltaS(0) of association are -30 kJ/mol and 
      13.1 J/molK. The large difference in DeltaS(0) of association of the different
      inhibitors suggests that the anomeric nitrogen atom of inhibitors 1-4 is involved
      in an interaction that results in a large entropy increase.

PMID- 11342047
TI  - Thermal stability of acetylcholinesterase from Bungarus fasciatus venom as
      investigated by capillary electrophoresis.
AB  - Previous studies on the conformation of the monomeric acetylcholinesterase (AChE)
      from the krait (Bungarus fasciatus) venom showed that the protein possesses a
      large permanent dipole moment. These studies predicted that thermal irreversible
      denaturation must occur via partially unfolded states. The thermal stability of
      Bungarus AChE was determined using capillary electrophoresis (CE) with optimized
      conditions. Runs performed at convenient temperature scanning rates provided
      evidence for an irreversible denaturation process according to the Lumry and
      Eyring model. The mid-transition temperature, T(m), and the effective enthalpy
      change, DeltaH(m) were determined at different pH. The temperature dependence of
      the free energy, DeltaG, of Bungarus AChE unfolding was drawn using values of
      T(m), DeltaH(m) and DeltaC(p) determined by CE. The thermodynamic parameters for
      the thermal denaturation of the monomeric snake enzyme were compared with those
      of different dimeric and tetrameric ChEs. It was shown that the changes in the
      ratio of DeltaH(cal/)DeltaH(vH) and DeltaC(p) reflect the oligomerization state
      of these proteins. All these results indicate that wild-type monomeric Bungarus
      AChE is a stable enzyme under standard conditions. However, designed mutants of
      this enzyme capable of degrading organophosphates have to be engineered to
      enhance their thermostability.

PMID- 11342049
TI  - Multiple unfolded states of alcohol dehydrogenase I from Kluyveromyces lactis by
      guanidinium chloride.
AB  - Inactivation, dissociation, and unfolding of tetrameric alcohol dehydrogenase I
      from Kluyveromyces lactis (KlADH I) were investigated using guanidinium chloride
      (GdmCl) as denaturant. Protein transitions were monitored by enzyme activity,
      intrinsic fluorescence and gel filtration chromatography. At low denaturant
      concentrations (less than 0.3 M), reversible transformation of enzyme into
      tetrameric inactive form occurs. At denaturant concentrations between 0.3 and 0.5
      M, the enzyme progressively dissociates into structured monomers through an
      irreversible reaction. At higher denaturant concentrations, the monomers unfold
      completely. Refolding studies indicate that a total reactivation occurs only with
      the enzyme denatured between 0 and 0.3 M GdmCl concentrations. The enzyme
      denatured at GdmCl concentrations higher than 0.3 M refolds only partially. All
      together, our results indicate that unfolding of the KlADH I is a multistep
      process, i.e., inactivation of the structured tetramer, dissociation into
      partially structured monomers, followed by complete unfolding.

PMID- 11342048
TI  - The chaperone-like activity of a small heat shock protein is lost after
      sulfoxidation of conserved methionines in a surface-exposed amphipathic alpha
      helix.
AB  - The small heat shock proteins (sHsps) possess a chaperone-like activity which
      prevents aggregation of other proteins during transient heat or oxidative stress.
      The sHsps bind, onto their surface, molten globule forms of other proteins,
      thereby keeping them in a refolding competent state. In Hsp21, a chloroplast
      located sHsp in all higher plants, there is a highly conserved region forming an
      amphipathic alpha-helix with several methionines on the hydrophobic side
      according to secondary structure prediction. This paper describes how
      sulfoxidation of the methionines in this amphipathic alpha-helix caused
      conformational changes and a reduction in the Hsp21 oligomer size, and a complete
      loss of the chaperone-like activity. Concomitantly, there was a loss of an outer
      surface located alpha-helix as determined by limited proteolysis and circular
      dichroism spectroscopy. The present data indicate that the methionine-rich
      amphipathic alpha-helix, a motif of unknown physiological significance which
      evolved during the land plant evolution, is crucial for binding of substrate
      proteins and has rendered the chaperone-like activity of Hsp21 very dependent on
      the chloroplast redox state.

PMID- 11342050
TI  - Ca(2+)-induced structural changes in rat m-calpain revealed by partial
      proteolysis.
AB  - Partial proteolysis by exogenous proteases in the presence and absence of Ca(2+)
      was used to map the protease-resistant domains in m-calpain, and to obtain
      evidence for the conformational changes induced in this thiol protease by Ca(2+).
      The complication of autoproteolysis was avoided by using the inactive Cys105Ser
      calpain mutant. Both trypsin and chymotrypsin produced similar cleavage patterns
      from the large subunit (domains I-IV), while the small subunit (domain VI) was
      largely unaffected. N-Terminal sequencing of the major products showed that
      hydrolysis occurred in the N-terminal anchor peptide, which binds domain I to
      domain VI, at a site close to the C terminus of domain II, and at several sites
      within domain III. Of particular importance to the overall Ca(2+)-induced
      conformational changes was the increase in mobility and accessibility of domain
      III. The same sites were cleaved in the presence and absence of Ca(2+), but with
      one exception digestion was much more rapid in the presence of Ca(2+). The
      exception was a site close to residue 255 located within the active site cleft.
      This site was accessible to cleavage in the absence of Ca(2+), when the active
      site is not assembled, but was protected in the presence of Ca(2+). This result
      supports the hypothesis that Ca(2+) induces movement of domains I and II closer
      together to form the functional active site of calpain.

PMID- 11342051
TI  - Different susceptibility of the two dimers of ribonuclease A to subtilisin.
      Implications for their structure.
AB  - RNase A and its minor and major dimers were digested with subtilisin under
      controlled conditions. The major dimer was found to be slightly more resistant,
      the minor dimer markedly less resistant to subtilisin than monomeric RNase A. Two
      S-proteins formed for each RNase A species, one starting with Ser-21, the other
      with Ser-22. Their relative proportions indicate that the structure of the minor
      dimer, whose identity with that of a RNase A dimer shown to be 3D domain-swapped
      is strongly suggested by recent work [S. Sorrentino et al. (2000) FEBS Lett. 466,
      35-39], makes its peptide bond between Ser-21 and Ser-22 more accessible to
      subtilisin than it is in RNase A and its major dimer. Moreover, (i) both subunits
      constituting the minor dimer are more susceptible to subtilisin than monomeric
      RNase A, and (ii) the susceptible bonds in one of its two exchanging N-terminal
      arms are more accessible to the protease than in the other. The properties of the
      major dimer suggest that its structure could be different.

PMID- 11342052
TI  - Understanding the role of internal lysine residues of serum albumins in
      conformational stability and bilirubin binding.
AB  - The role of internal lysine residues of different serum albumins, viz. from
      human, rabbit, goat, sheep and buffalo (HSA, RbSA, GSA, SSA and BuSA), in
      conformational stability and bilirubin binding was investigated after blocking
      them using acetylation, succinylation and guanidination reactions. No significant
      change in the secondary structure was noticed whereas the tertiary structure of
      these proteins was slightly altered upon acetylation or succinylation as revealed
      by circular dichroism (CD), fluorescence and gel filtration results.
      Guanidination did not affect the native protein conformation to a measurable
      extent. Scatchard analysis, CD and absorption spectroscopic results showed marked
      reductions (5-21-fold decrease in K(a) and approximately 50% decrease in the CD
      Cotton effect intensity) in the affinity of albumins for bilirubin upon
      acetylation or succinylation whereas guanidination produced a small change.
      Interestingly, monosignate CD spectra of bilirubin complexed with GSA, SSA and
      BuSA were transformed to bisignate CD spectra upon acetylation or succinylation
      of internal lysine residues whereas spectra remained bisignate in the case of
      bilirubin bound to acetylated or succinylated derivatives of HSA and RbSA. When
      probed by CD spectroscopy, bilirubin bound to acetylated or succinylated
      derivatives of GSA and SSA rapidly switched over to native albumins and not vice
      versa. These results suggested that salt linkage(s) contributed by internal
      lysine residue(s) play an important role in the high-affinity binding of
      bilirubin to albumin and provide stability to the native three-dimensional
      conformation of the bound pigment. Chloroform severely decreased the intensity of
      both positive and negative CD Cotton effects of bilirubin complexed with
      acetylated or succinylated derivatives of all albumins which otherwise increased
      significantly in the case of bilirubin complexed with native and guanidinated
      albumin derivatives, except the bilirubin-RbSA complex which showed a small
      decrease in intensity. These results suggest that the presence of salt linkage(s)
      in bilirubin-albumin complexation is(are) crucial to bring about effective and
      efficient stereochemical changes in the bound pigment by co-binding of chloroform
      which seems to have at least one conserved binding site on these albumins that is
      shared with bilirubin.

PMID- 11342053
TI  - Structural determinants influencing the reaction of cysteine-containing peptides
      with palmitoyl-coenzyme A and other thioesters.
AB  - Non-enzymatic thioesterification of specific cysteinyl peptides with fatty acyl
      CoA has been previously demonstrated in both liposomes and aqueous medium. To
      identify the molecular basis for the differential reactivity of polypeptides in
      aqueous solutions, 26 synthetic cysteinyl peptides encompassing the
      palmitoylation sites of well known proteins (protein zero, proteolipid protein,
      beta-adrenergic receptor, p21(K-ras), transferrin receptor, CD-4 and SNAP-25) and
      six small thiol compounds were incubated separately with [3H]palmitoyl-CoA,
      [14C]acetyl-CoA and p-nitrophenyl thioacetate (NPTA). For each peptide, both the
      observed reaction rate constant at pH 7.5 and the pH-independent rate constant
      (k(2)) were calculated, and reactivity of the attacking sulfhydryl group was
      characterized using the Bronsted equation (log k(2)=beta(nuc) pK(a)+C). In
      general, peptides bearing basic and aromatic amino acid residues showed the
      lowest thiol pK(a)s, and consequently displayed the highest acylation rates.
      Reaction with palmitoyl-CoA was complicated to analyze because of the variable
      partition of peptides in the acyl chain donor/detergent micelles. In contrast, a
      linear Bronsted relationship was found for the reaction of the peptides with the
      water-soluble acetyl-CoA (beta(nuc)=0.59). A similar beta(nuc) value was obtained
      with the neutral NPTA, indicating that electronic effects other than those
      responsible for the acid-base properties of the thiol are less important. Thus,
      the concentration of the thiolate anion appears to be the major factor
      influencing the rate of the nucleophilic substitution reaction. These findings
      and the fact that the acylation sites in most proteins are surrounded by basic
      amino acids may partially explain the specificity of non-enzymatic palmitoylation
      regarding the acceptor sequences.

PMID- 11342054
TI  - Full-length and truncated forms of vitronectin provide insight into effects of
      proteolytic processing on function.
AB  - A genetic polymorphism in the vitronectin allele directs the production of two
      distinct forms of the 459 amino acid glycoprotein. A methionine present at
      position 381 favors production of the single-chain form of vitronectin, while
      threonine at this position increases the susceptibility of vitronectin to
      cleavage just beyond its heparin-binding domain at residue 379. This reaction
      gives rise to a disulfide-bonded, two-chain form of vitronectin. In order to
      investigate the functional significance of the vitronectin polymorphism, the
      baculovirus system has been used to express recombinant full-length vitronectin
      and a truncated form of the molecule that represents the 62-kDa fragment of two
      chain vitronectin. Both forms of vitronectin bind and neutralize heparin
      anticoagulant activity. The proteins also bind PAI-1 and stabilize its active
      conformation. These experiments suggest that the C-terminal 80 amino acids do not
      confer a functional difference in the two allelic variants. Immunoassays and gel
      filtration experiments indicate that both full-length and truncated recombinant
      forms of vitronectin are multimeric. Together with other reports from this
      laboratory, these results provide information regarding the primary binding sites
      for two vitronectin ligands and further define regions that may be involved in
      multimerization of the protein.

PMID- 11342055
TI  - Reactivation and refolding of rabbit muscle creatine kinase denatured in 2,2,2
      trifluoroethanol solutions.
AB  - The unfolding and refolding of creatine kinase (ATP:creatine N-phosphotransferase
      (CK), EC 2.7.3.2) during denaturation and reactivation by trifluoroethanol (TFE)
      have been studied. Significant aggregation was observed when CK was denatured at
      TFE concentrations between 10% and 40% (v/v). 50% TFE (v/v) was used to study the
      denaturation and unfolding of CK. The activity loss of CK was a very quick
      process, as was the marked conformational changes during denaturation followed by
      fluorescence emission spectra and far-ultraviolet CD spectra. DTNB modification
      and size exclusion chromatography were used to find that CK dissociated and was
      in its monomer state after denaturation with 50% TFE. Reactivation and refolding
      were observed after 80-fold dilution of the denatured CK into 0.05 M Tris-HCl
      buffer, pH 8.0. The denatured CK recovered about 38% activity following a two
      phase course (k(1)=4.82+/-0.41x10(-3) s(-1), k(2)=0.60+/-0.01x10(-3) s(-1)).
      Intrinsic fluorescence maximum intensity changes showed that the refolding
      process also followed biphasic kinetics (k(1)=4.34+/-0.27x10(-3) s(-1),
      k(2)=0.76+/-0.02x10(-3) s(-1)) after dilution into the proper solutions. The far
      ultraviolet CD spectra ellipticity changes at 222 nm during the refolding process
      also showed a two phase course (k(1)=4.50+/-0.07x10(-3) s(-1), k(2)=1.13+/
      0.05x10(-3) s(-1)). Our results suggest that TFE can be used as a reversible
      denaturant like urea and GuHCl. The 50% TFE induced CK denaturation state, which
      was referred to as the 'TFE state', and the partially refolded CK are compared
      with the molten globule state. The aggregation caused by TFE during denaturation
      is also discussed in this paper.

PMID- 11342056
TI  - Acyl-CoA-binding protein in the armadillo Harderian gland: its primary structure
      and possible role in lipid secretion.
AB  - Similar to those of other species, the Harderian glands of armadillo produce an
      abundant lipid secretion, most of which is composed of 1-alkyl-2,3
      diacylglycerol. Biosynthesis of this component is apparently performed with the
      participation of one cytosolic pool of acyl-CoA and another of free fatty acids.
      The acyl-CoA-binding protein (ACBP) is present at a concentration at least 7-fold
      that of the heart-type fatty acid-binding protein (H-FABP), though lower than
      that in other armadillo organs such as liver and brain. The ACBP complete amino
      acid sequence was determined by Edman degradation of peptides generated by
      cleavage of the protein with cyanogen bromide, endopeptidase Glu-C, and trypsin.
      ACBP consists of 86 residues and has a calculated molecular mass of 9783 Da,
      taking into account that an acetyl group is blocking the N-terminus. Identity
      percentages between armadillo Harderian gland ACBP and other known ACBPs show
      that the protein belongs to the liver-specific ACBP isoform (L-ACBP). The fact
      that the ACBP concentration is higher than that of FABP suggests that the
      Harderian gland is able to store acyl-CoA amounts in ACBP larger than those of
      fatty acids in H-FABP for 1-alkyl-2,3-diacylglycerol synthesis.

PMID- 11342057
TI  - Homotropic cooperative binding of organic solvent vapors by solid trypsin.
AB  - Homotropic cooperative binding was observed at vapor sorption of organic solvents
      (acetonitrile, propionitrile, ethanol, 1-propanol, 2-propanol, nitroethane) by
      dried solid trypsin from porcine pancreas (0.05 g H2O/g protein). The vapor
      sorption isotherms were obtained by the static method of gas chromatographic
      headspace analysis at 298 K for 'vapor solvent+solid trypsin' systems in the
      absence of the liquid phase. All isotherms have a sigmoidal shape with
      significant sorbate uptake only above the threshold of sorbate thermodynamic
      activity. On the sorption isotherms of non-hydroxylic sorbates the saturation of
      trypsin by organic solvent was observed above the sorbate threshold activity. The
      formation of inclusion compounds with phase transition between solvent-free and
      solvent-saturated trypsin is supposed. Approximation of obtained isotherms by the
      Hill equation gives the inclusion stoichiometry S, inclusion free energy, and the
      Hill constant N of clathrates. The inclusion stoichiometry S depends
      significantly on the size and shape of sorbate molecules and changes from S=31
      mol of sorbate per mol of trypsin for ethanol to S=6 for nitroethane. The
      inclusion free energies determined for the standard states of pure liquid sorbate
      and infinitely dilute solution in toluene are in the range from -0.5 to -1.2
      kJ/mol and from -3.1 to -8.1 kJ/mol, respectively, per 1 mol of sorbate. The Hill
      constants are relatively high: from N=5.6 for 1-propanol to N approximately equal
      to 10(3) for nitroethane. The implication of the obtained results for the
      interpretation of solvent effects on the enzyme activity and stability in low
      water medium is discussed.

PMID- 11342058
TI  - Reactions of soybean peroxidase and hydrogen peroxide pH 2.4-12.0, and veratryl
      alcohol at pH 2.4.
AB  - Peroxidase from soybean seed coat (SBP) has properties that makes it particularly
      suited for practical applications. Therefore, it is essential to know its
      fundamental enzymatic properties. Stopped-flow techniques were used to
      investigate the pH dependence of the reaction of SBP and hydrogen peroxide. The
      reaction is linearly dependent on hydrogen peroxide concentration at acidic and
      neutral pH with the second order rate constant k(1)=2.0x10(7) M(-1) s(-1), pH 4
      8. From pH 9.3 to 10.2 the reaction is biphasic, a novel observation for a
      peroxidase at alkaline pH. A fast reaction has the characteristics of the
      reaction at neutral pH, and a slow reaction shows hyperbolic dependence on
      hydrogen peroxide concentration. At pH >10.5 only the slow reaction is seen. The
      shift in mechanism is coincident with the change in haem iron co-ordination to a
      six-coordinate low spin hydroxy ligated alkaline form. The pK(a) value for the
      alkaline transition was observed at 9.7+/-0.1, 9.6+/-0.1 and 9.9+/-0.2 by
      spectrophotometric titration, the fast phase amplitude, and decrease in the
      apparent second order rate constant, respectively. An acidic pK(a) at 3.2+/-0.3
      was also determined from the apparent second order rate constant. The reactions
      of soybean peroxidase compounds I and II with veratryl alcohol at pH 2.44 give
      very similar second order rate constants, k(2)=(2.5+/-0.1)x10(4) M(-1) s(-1) and
      k(3)=(2.2+/-0.1)x10(4) M(-1) s(-1), respectively, which is unusual. The
      electronic absorption spectra of compounds I, II and III at pH 7.07 show
      characteristic bands at 400 and 651 nm (compound I), 416, 527 and 555 nm
      (compound II), and 414, 541 and 576 nm (compound III). No additional
      intermediates were observed.

PMID- 11342059
TI  - Enzyme activity determination on macromolecular substrates by isothermal
      titration calorimetry: application to mesophilic and psychrophilic chitinases.
AB  - Isothermal titration calorimetry has been applied to the determination of the
      kinetic parameters of chitinases (EC 3.2.1.14) by monitoring the heat released
      during the hydrolysis of chitin glycosidic bonds. Experiments were carried out
      using two different macromolecular substrates: a soluble polymer of N
      acetylglucosamine and the insoluble chitin from crab shells. Different
      experimental temperatures were used in order to compare the thermodependence of
      the activity of two chitinases from the psychrophile Arthrobacter sp. TAD20 and
      of chitinase A from the mesophile Serratia marcescens. The method allowed to
      determine unequivocally the catalytic rate constant k(cat), the activation energy
      (E(a)) and the thermodynamic activation parameters (DeltaG(#), DeltaH(#),
      DeltaS(#)) of the chitinolytic reaction on the soluble substrate. The catalytic
      activity has also been determined on insoluble chitin, which displays an effect
      of substrate saturation by chitinases. On both substrates, the thermodependence
      of the activity of the psychrophilic chitinases was lower than that observed with
      the mesophilic counterpart.

PMID- 11342060
TI  - NO donors inhibit Leishmania infantum cysteine proteinase activity.
AB  - Nitric oxide (NO) releasing drugs (e.g., glyceryl trinitrate) were successfully
      used in the treatment of cutaneous leishmaniasis in man. In the present study,
      the effect of NO donors on the catalytic activity of the cysteine proteinase from
      promastigotes of Leishmania infantum, an agent of Old World visceral and
      cutaneous leishmaniases, is reported. In particular, one equivalent of NO,
      released by the NO donors S-nitrosoglutathione, glyceryl trinitrate, (+/-)-(E)-4
      ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide, 3-morpholinosydnonimine, S
      nitrosoacetylpenicillamine and sodium nitroprusside, inhibited one equivalent of
      the parasite cysteine proteinase. As expected, NO-deprived compounds did not
      affect the catalytic activity of the parasite cysteine proteinase. Furthermore,
      the absorption spectrum of the (+/-)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3
      hexenamide-treated inactive L. infantum enzyme displayed a maximum in the 330-350
      nm wavelength range. The reducing agents dithiothreitol and L-ascorbic acid
      completely prevented parasite cysteine proteinase inhibition by NO, fully
      restored the catalytic activity, and reversed the NO-induced absorption spectrum
      of the inactive enzyme. Moreover, S-nitrosoacetylpenicillamine displayed a
      leishmanicidal effect, inhibiting the cysteine proteinase activity in vivo. As
      expected, the NO-deprived compound N-acetylpenicillamine did not affect
      significantly the parasite viability and the enzyme activity in vivo. These data
      suggest that the L. infantum cysteine proteinase undergoes NO-mediated S
      nitrosylation, thereby representing a possible mechanism of antiparasitic host
      defence.

PMID- 11342061
TI  - Nucleotide and deduced amino acid sequences of an alkaline pullulanase from the
      alkaliphilic bacterium Bacillus sp. KSM-1876.
AB  - The nucleotide sequence of an alkaline pullulanase-encoding gene from
      alkaliphilic Bacillus sp. strain KSM-1876 was determined. The open reading frame
      of the gene encoded 1142 amino acids with a calculated molecular mass of 128739
      Da. The alkaline pullulanase showed very limited homology (<32% identity) to
      previously reported debranching enzymes from prokaryotes and eukaryotes. It
      contained unique tandem repeats in both the N-terminal and the C-terminal
      regions.

PMID- 11342063
TI  - Editor's note.

PMID- 11342062
TI  - Preliminary cryocrystallography analysis of an eumenine mastoparan toxin isolated
      from the venom of the wasp Anterhynchium flavomarginatum micado.
AB  - Mastoparans are tetradecapeptides found to be the major component of vespid
      venoms. These peptides present a wide spectrum of biological activities, such as
      mast cell degranulation, hemolytic activity and also reveals antimicrobial
      activity. A mastoparan toxin isolated from the venom of Anterhynchium
      flavomarginatum micado has been crystallized. At room temperature these crystals
      diffracted to 2.8 A resolution. However, upon cooling to cryogenic temperature
      around 85 K, the original resolution limit could be improved to 2.0 A. Crystals
      were determined to belong to the space group P3(1) (P3(2)). This is the first
      mastoparan to be crystallized and it will provide further insights in the
      conformational significance of mastoparan toxins, with respect to their potency
      and activity in G protein regulation.

PMID- 11342064
TI  - Consultation section: refractive surgical problem.

PMID- 11342066
TI  - Consultation section: refractive surgical problem.

PMID- 11342065
TI  - Consultation section: refractive surgical problem.

PMID- 11342067
TI  - Consultation section: refractive surgical problem.

PMID- 11342069
TI  - Consultation section: refractive surgical problem.

PMID- 11342068
TI  - Consultation section: refractive surgical problem.

PMID- 11342070
TI  - Consultation section: refractive surgical problem.

PMID- 11342071
TI  - Consultation section: refractive surgical problem.

PMID- 11342093
TI  - New Frontiers 2001.

PMID- 11342094
TI  - Low molecular weight heparin and neuraxial anesthesia.
AB  - Spinal and epidural anesthesia/analgesia provide several advantages over systemic
      opioids, including superior analgesia, reduced blood loss and need for
      transfusion, and decreased incidence of thromboembolic complications. However,
      patients hospitalized for major surgery often receive an anticoagulant and/or
      antiplatelet medication perioperatively to prevent venous thrombosis and
      pulmonary embolism, although the pharmacologic agent, degree of anticoagulation
      desired, and duration of therapy remain controversial. These patients are often
      not considered candidates for spinal or epidural anesthesia/analgesia because of
      a theoretically greater risk of spinal hematoma. Spinal hematoma is a rare and
      potentially catastrophic complication of spinal or epidural anesthesia. The
      incidence of neurologic dysfunction resulting from hemorrhagic complications
      associated with central neural blockade is estimated to be less than 1 in 150,000
      epidural and less than 1 in 220,000 spinal anesthetics. The decision to perform
      neuraxial blockade on these patients must be made on an individual basis,
      weighing the risk of spinal hematoma from needle or catheter placement against
      the theoretical benefits gained. Familiarity with the pharmacology of hemostasis
      altering drugs, as well as case reports and clinical studies involving patients
      undergoing neuraxial blockade while receiving these medications will guide the
      clinician faced with this difficult decision.

PMID- 11342095
TI  - Low-molecular-weight heparin prophylaxis: preoperative versus postoperative
      initiation in patients undergoing elective hip surgery.
AB  - Administration of low-molecular-weight heparin prophylaxis in elective hip
      implant patients commonly begins 12 h preoperatively in European practices to
      optimize effectiveness, and 12 to 24 h postoperatively in North American
      practices to optimize safety. A meta-analysis comparing these two treatment
      regimes revealed that preoperative initiation demonstrated greater efficacy and
      superior safety for patients (10.0% rate of total deep-vein thrombosis vs. 15.3%,
      P = .023). In addition to the pre/postsurgical debate, proximity of initiation of
      low-molecular-weight heparin in relation to surgery is an issue of critical
      importance. Recent studies revealed that beginning therapy immediately within 2 h
      preoperatively or 6 h postoperatively dramatically decreased the risk of venous
      thrombosis. An investigation of low-molecular-weight heparin prophylaxis
      initiated 2 h before elective hip surgery or approximately 6 h after surgery
      compared with warfarin sodium revealed that total and proximal deep-vein
      thrombosis rates were reduced in patients receiving low-molecular-weight heparin
      compared with warfarin. The frequencies of deep-vein thrombosis for patients
      receiving preoperative and postoperative dalteparin vs. warfarin for all deep
      vein thrombosis were 36 of 337 (10.7%, P < .001) and 44 of 336 (13.1%, P < .001)
      vs. 81 of 338 (24.0%); and for proximal deep-vein thrombosis were 3 of 354 (0.8%,
      P = .035) and 3 of 358 (0.8%, P = .033) vs. 11 of 363 (3.0%). Relative risk
      reductions for the dalteparin groups vs. warfarin ranged from 45% to 72%. In this
      case, low-molecular-weight heparin administered in close proximity to surgery
      provided superior efficacy over warfarin. Major bleeding was significantly
      increased with the preoperative regimen but not the postoperative regimen.

PMID- 11342096
TI  - Low-molecular-weight heparin: the optimal duration of prophylaxis against
      postoperative venous thromboembolism after total hip or knee replacement.
AB  - Venous thromboembolism is a major health problem. In about 20% of cases, the
      initial clinical manifestation of venous thromboembolism is sudden death due to
      pulmonary embolism. Consequently, appropriate prophylaxis is critical in order to
      improve survival. Because patients with recent surgery have a 22-fold increased
      risk of postoperative venous thromboembolism, a large research effort has been
      directed toward identifying the safest and most effective prophylaxis after
      surgery, especially after total hip or knee replacement. While low-molecular
      weight heparin is the most effective prophylaxis currently available, from 15% to
      30% of hip or knee replacement patients still develop deep vein thrombosis by the
      time of hospital discharge, and another 25% develop new deep vein thrombosis by 3
      weeks after discharge. Extended out-of-hospital low-molecular-weight heparin
      prophylaxis can safely reduce the prevalence of deep vein thrombosis by about
      50%. However, essentially all of these thrombi are small, asymptomatic, and
      resolve without serious clinical sequelae. Based on one clinical trial, out-of
      hospital low-molecular-weight heparin prophylaxis could reduce the incidence of
      symptomatic venous thromboembolism or all-cause death after discharge by a
      maximum of 2.2%. At current drug costs, universal out-of-hospital low-molecular
      weight heparin prophylaxis is unlikely to be cost-effective. For most patients, 7
      to 10 days of low-molecular-weight heparin prophylaxis is adequate. Future
      research should be directed at identifying patients at risk for out-of-hospital
      venous thromboembolism, and targeting extended prophylaxis to those at highest
      risk.

PMID- 11342097
TI  - Low-molecular-weight heparin during pregnancy.
AB  - Thromboembolism is an infrequent, yet serious cause of both maternal and fetal
      morbidity and death during pregnancy and the puerperium. Pregnancy itself
      increases the risk of thromboembolic complications probably owing to a
      combination of hypercoagulability and venous stasis due to venous dilation.
      Recent studies have indicated that some serious obstetric complications are
      correlated with inherited or acquired thrombophilia. The prevalence of venous
      thromboembolism (VTE) has been extimated to be 1 per 1000-2000 pregnancies in
      retrospective studies. Anticoagulant treatment and prophylaxis both before and
      during pregnancy are based on unfractionated heparin (UH), low-molecular-weight
      heparin (LMWH) and warfarin. Warfarin is teratogenous if administered between the
      6th and the 12th week. LMWH is replacing UH in the prevention and treatment of
      VTE both outside and more recently during pregnancy with the same indications,
      and also for obstetric complications. This paper assesses the safety and efficacy
      of heparin therapy during pregnancy and the puerperium. Its cardiovascular and
      obstetric indications and regimens and maternal and fetal side-effects are also
      discussed.

PMID- 11342098
TI  - Positive and negative regulation of squalene synthase (ERG9), an ergosterol
      biosynthetic gene, in Saccharomyces cerevisiae.
AB  - To identify regulatory cis-elements in the proximal promoter of the yeast ERG9
      squalene synthase gene, promoter deletion analysis was performed. This approach
      identified two regulatory elements, one an upstream repressing cis-element (URS),
      and the other an upstream activating cis-element (UAS). Electromobility shift
      assays (EMSAs) demonstrated that distinct proteins bind each element. Genetic
      screens were performed to identify yeast mutants that altered expression of ERG9
      promoter-reporter gene fusions. Three non-ergosterol biosynthetic pathway genes
      were identified. A mutation in TPO1(YLL028W) led to a 5.5-fold increase in ERG9
      expression while mutations in YER064C and SLK19 (YOR195W) led to a 3.1- and 5.6
      fold decrease, respectively. Deletion analysis of these genes demonstrated that
      TPO1 and SLK19 specifically regulated ERG9 expression when tested with several
      different promoter-reporter gene fusions. Additionally, EMSAs demonstrated that
      extracts derived from the TPO1 deletion strain was unable to shift the repressing
      cis-element while protein extracts from the SLK19 deletion strain had a reduced
      shift of the activating cis-element. Furthermore, these two mutants showed
      quantitative differences in sterols and antifungal drug susceptibilities
      consistent with their role in regulating ERG9 expression.

PMID- 11342099
TI  - Identification and distribution of CCK-related peptides and mRNAs in the rainbow
      trout, Oncorhynchus mykiss.
AB  - Peptides homologous to mammalian cholecystokinin (CCK), and their corresponding
      cDNAs, have been isolated and sequenced from the rainbow trout, Oncorhynchus
      mykiss. Three cDNAs encoding CCK-like preprohormones were identified from the
      brain. The cDNAs encode three different putative CCK-8 peptides containing Asn,
      Leu or Thr, in position 6 (counting from the C-terminus). Hence, the trout CCKs
      are named CCK-N, CCK-L and CCK-T respectively. RT-PCR showed differential
      expression of the three mRNAs although all were detected in the brain and
      intestine, similar to the expression pattern of CCK in tetrapods. In situ
      hybridization on trout brain sections using (35)S-labeled gene-specific antisense
      oligonucleotides showed that the three mRNAs were present in different parts,
      suggesting that the three CCK peptides may have different functions in the brain.
      Purification of CCK-immunoreactive material from the trout brain resulted in two
      CCK octapeptides: DYNGWMDF(.)NH2 (CCK-N) and DYLGWMDF(.)NH2 (CCK-L) present in
      equal amounts. In the pyloric caeca, three forms of CCK-L were identified,
      consisting of 7, 8 and 21 residues, respectively. The last was dominating and had
      the sequence ASGPGPSHKIKDRDYLGWMDF(.)NH2. All isolated peptides were fully
      sulfated. The trout is the first species in which three different CCK-like cDNAs
      have been identified.

PMID- 11342100
TI  - The rainbow trout metallothionein-B gene promoter: contributions of distal
      promoter elements to metal and oxidant regulation.
AB  - In this report, the contributions of the distal 5'-regulatory sequences of the
      rainbow trout (Oncorhynchus mykiss) metallothionein (tMT)-B gene promoter (-738
      to +5) were studied. Transfection of the -738 promoter fragment in a rainbow
      trout hepatoma cell line (RTH-149) resulted in 4- to 5-fold greater activity
      compared to the proximal -137 promoter region. Mutation of the proximal MREa
      abolishes the basal activity of the -738 fragment indicating that the distal
      regulatory elements require a cooperative interaction with MREa. However, the
      fragments containing both distal MREs, c and d (positioning -570 and -680,
      respectively), or MREc alone could confer basal and metal-induced activity when
      fused to the TATA box. This suggests that these distal elements are functional
      and therefore may play a role as basal elements in their natural state. The trout
      MT genes are also induced by oxidants including H2O2, tBHP and tBHQ. The larger
      promoter fragment -738 responds to H2O2, while the -137 fragment does not.
      However, fusion of the isolated MREc fragment (-648 to -533) in its native
      orientation, upstream of the -137 promoter elicits a response to H2O2, although
      no response is seen with MREc in reverse. These data suggest that this distal
      fragment contains functional oxidant responsive elements which have resemblance
      to the mammalian antioxidant responsive element (AREs).

PMID- 11342101
TI  - TCF11/Nrf1 overexpression increases the intracellular glutathione level and can
      transactivate the gamma-glutamylcysteine synthetase (GCS) heavy subunit promoter.
AB  - Gamma-glutamylcysteinylglycine or glutathione (GSH) performs important protective
      functions in the cell through maintenance of the intracellular redox balance and
      elimination of xenobiotics and free radicals. The production of GSH involves a
      number of enzymes and enzyme subunits offering multiple opportunities for
      regulation. Two members of the CNC subfamily of bZIP transcription factors
      (TCF11/Nrf1 and Nrf2) have been implicated in the regulation of detoxification
      enzymes and the oxidative stress response. Here we investigate the potential role
      of one of these factors, TCF11/Nrf1, in the regulation of GSH levels in the cell
      and particularly its influence on the expression of one of the enzymatic
      components necessary for the synthesis of GSH, the heavy subunit of gamma
      glutamylcysteine synthetase (GCS(h)). Using overexpression of the transcription
      factor in COS-1 cells we show that TCF11/Nrf1 stimulates GSH accumulation. Using
      co-transfection with reporter constructs where reporter expression is driven
      through the GCS(h) promoter we show that this increase may be mediated in part by
      induced expression of the GCS(h) gene by TCF11/Nrf1. We further show that a
      distal portion of the promoter including two antioxidant-response elements (AREs)
      predominantly mediates the TCF11/Nrf1 transactivation and an electromobility
      shift assay showed that just one of these AREs specifically binds TCF11/Nrf1 as
      heterodimers with small Maf proteins. We suggest that TCF11/Nrf1 can operate
      through a subset of AREs to modulate the expression of GCS(h) together with other
      components of the pathway and in this way play a role in regulating cellular
      glutathione levels.

PMID- 11342102
TI  - Binding mode of 4',6-diamidino-2-phenylindole and ethidium to
      poly(dG).poly(dC).poly(dC)(+) triplex and poly(dG).poly(dC) duplex.
AB  - Optical spectroscopic properties of 4',6-diamidino-2-phenylindole (DAPI) and
      ethidium bromide complexed with poly(dG).poly(dC).poly(dC)(+) triplex and
      poly(dG).poly(dC) duplex were compared in this study. When complexed with both
      duplex and triplex, ethidium is characterized by hypochromism and a red shift in
      the absorption spectrum, a complicate induced circular dichroism (CD) band in the
      polynucleotide absorption region, and a negative reduced linear dichroism signal
      in both polynucleotide and drug absorption regions. The spectral properties for
      both duplex- and triplex-bound ethidium are identical and both can be understood
      by the intercalation binding mode. In contrast, the absorption and CD spectra of
      DAPI complexed with triplex differ from those of the DAPI-duplex complex,
      although both complexes can be understood by the intercalation binding mode.
      Considering that the third strand runs along the major groove of the template
      duplex, we conclude that the DAPI molecule partially intercalates near the major
      groove of the duplex, where the third strand can affect its spectroscopic
      properties.

PMID- 11342103
TI  - Genomic organization of a human 5beta-reductase and its pseudogene and substrate
      selectivity of the expressed enzyme.
AB  - The enzyme 5beta-reductase catalyzes the reduction of the 4-ene of 3
      ketosteroids, converting them into 5beta-dihydro-3-ketosteroids and, thus, could
      be involved in the metabolism of 4-cholestene-3-one, progesterone, 17~
      hydroxyprogesterone, aldosterone, corticosterone, cortisol, 4-androstenedione,
      and testosterone. In this study, we report the genomic structure of a human 5beta
      reductase gene, its tissue distribution, the characterization of an intronless
      pseudogene and the substrate selectivity of the enzyme. The gene coding for the
      active 5beta-reductase contains nine exons like most members of the aldo-keto
      reductase family, but the sequence covered by the gene, more than 42 kb, is much
      longer than the sequence of other members of this family. There are many large
      introns, especially introns 3, 4 and 7 that span approx. 7 kb, and intron 1 that
      contains more than 10 kb. Northern blot analysis showed three band sizes of 1.3,
      2.2 and 2.7 kb. The 1.3 and 2.7 kb bands are highly expressed in the liver while
      weaker 2.2 and 1.3 kb bands have been observed in the testis and colon,
      respectively. We also identified an intronless gene having 86% homology with the
      5beta-reductase cDNA sequence. Since its sequence contains many stop codons, this
      gene is most probably a pseudogene. To determine more precisely the substrate
      selectivity of the enzyme, we established a stable cell line expressing human
      5beta-reductase in transformed embryonic kidney (HEK-293) cells. The transfected
      cells efficiently catalyze the transformation of progesterone, androstenedione,
      17alpha-hydroxyprogesterone and testosterone. However, they catalyze much less
      efficiently the transformation of compounds containing an 11beta-hydroxy group,
      such as aldosterone, corticosterone and cortisol. In addition to its role in
      cholesterol catabolism, it is well recognized that 5beta-reductase inactivates
      active androgens. Indeed, 5beta-dihydrotestosterone (5beta-DHT), the product of
      the reduction of testosterone by 5beta-reductase, is not active while its 5~
      isomer (DHT) is the most potent natural androgen. Recent findings show that 5beta
      pregnanes are active ligands in the induction of CYP3A through the orphan
      receptor hPAR. Our results thus open an opportunity for studying the new role of
      5beta-reductase in the formation of a new type of active steroids.

PMID- 11342104
TI  - Characterization of an enhancer element in the proximal promoter of the mouse
      glucagon receptor gene.
AB  - The 5'-flanking region of the mouse glucagon receptor has been previously cloned
      and two promoter regions were characterized. Functional analysis of the proximal
      promoter was now performed to characterize cis-acting element(s) regulating basal
      gene expression. Promoter analysis using deletion constructs in a rat cell line
      (CA-77) expressing the glucagon receptor, showed that the region from -64 to +127
      relative to the proximal transcription start site was sufficient for maximal
      proximal promoter activity. A DNA sequence spanning the -28 to -16 region
      organized as an imperfect palindrome was demonstrated to be functional as a cis
      acting enhancer. Constructs including several copies of this motif strongly
      increased activity of the heterologous thymidine kinase promoter. Gel mobility
      shift assays performed with different DNA fragments spanning this region
      confirmed that it specifically bound nuclear protein(s) from CA-77 cells, mouse
      MIN-6 cells or mouse liver. Mutations in the core sequence of this site impaired
      both reporter gene activity and nuclear protein binding. The palindrome is a
      novel DNA sequence with no homology to existing transcription factor binding site
      database. This is the first characterization of a functional cis-acting sequence
      into the proximal promoter of the mouse glucagon receptor that may support
      constitutive expression of the gene.

PMID- 11342105
TI  - Identification of a growth phase-dependent promoter in the rplJL operon of
      Streptomyces coelicolor A3(2).
AB  - A single promoter, rplJp (P(L10)), has been identified in the rplJL operon from
      Streptomyces coelicolor A3(2) by promoter probe and primer extension analyses.
      P(L10) is located upstream of the rplL gene and of the DNA encoding the mRNA
      leader region that contains the putative L10 (or L10.L12(4)) binding site for
      translational autogenous regulation. The potential start point for transcription
      was found 239 nucleotides upstream of the predicted translational start codon of
      rplJ. The promoter sequence shows -35 and -10 hexamers that resemble those of
      Streptomyces consensus Escherichia coli sigma(70)-like promoters and the rplJp
      from Streptomyces griseus. The amount of the transcript detected by primer
      extension analysis decreases during growth immediately after the transition
      phase, a slowdown in growth occurring during exponential phase associated with
      increases in ppGpp level. The temporal pattern of transcripts shows a clear
      correlation with the temporal pattern of L10 and L7/L12 protein synthesis
      reported in previous kinetic studies. This indicates that P(L10) is a growth
      phase-dependent promoter which may contribute, together with translational
      regulation, to the decrease in the synthesis of L10 and L7/L12 observed in liquid
      minimal medium. This is supported by results of promoter probe experiments.
      Although no significant promoter activity has been found by promoter probing in
      the rplJ and rplL intergenic region, an additional 5'-transcript end was detected
      by primer extension, probably as a result of mRNA processing event from a longer
      transcript. This may be required to maintain the 1:4 ratio observed for L10 and
      L7/L12 in the ribosomes.

PMID- 11342106
TI  - Epidermal growth factor induces Gadd45 (growth arrest and DNA damage inducible
      protein) expression in A431 cells.
AB  - Epidermal growth factor (EGF) receptor over-expressing, p53-deficient A431 cells
      response to toxic dose of EGF by G1 arrest and apoptosis. Applying cDNA
      expression array technology we demonstrated that EGF increased the levels of
      Gadd45 mRNA. Northern blot and Western blot analyses confirmed that both Gadd45
      mRNA and protein were increased. Concurrently half-lives of Gadd45 mRNA and
      protein also increased. Nuclear run-on experiments did not show a large increase
      of Gadd45 mRNA transcription rate. Gadd45 mRNA and protein started to increase
      after 1 h of EGF treatment and remained high for up to 10 h. We have also
      confirmed previous studies which showed that in EGF-stimulated A431 cells
      p21(Cip1/Waf1) (cyclin-dependent kinase interacting protein 1) was up-regulated
      within the same time frame. Thus it appears that in addition to inducing G2
      arrest by directly disrupting Cdc2/Cyclin B1 complex in genotoxic-stressed cells,
      Gadd45 may also participate in G1 arrest in growth factor overexposed cells.

PMID- 11342107
TI  - Rat adrenoleukodystrophy-related (ALDR) gene: full-length cDNA sequence and new
      insight in expression.
AB  - X-linked adrenoleukodystrophy (X-ALD) is an inherited demyelinating disorder due
      to mutations in the ALD gene, which encodes a peroxisomal ABC half-transporter
      (ALDP). It has been suggested that ALDP assembles with ALDRP
      (adrenoleukodystrophy-related protein), a close homologous half-transporter, to
      form a functional heterodimer. For the first time full-length ALDRP cDNA (5.5 kb)
      was cloned, and 5' and 3' RACE analysis revealed that alternative usage of
      polyadenylation sites generates the two transcripts of 3.0 and 5.5 kb observed in
      the rat in Northern blot analysis. Southern blotting and chromosomal mapping
      demonstrated one ALDR locus in the rat genome. Characterisation of the 3'
      flanking region suggested that an ID sequence might be responsible for high
      expression of the 5.5 kb ALDRP transcript in rat brain. ALDR gene expression was
      found to be high in the liver of rats before weaning and very low in adult rats;
      the reverse developmental regulation was observed in the brain. Fenofibrate,
      which is a potent inducer of the ALDR gene in the liver of adult rats, could not
      induce the ALDR gene in suckling rats. The exact significance of this result with
      regard to development of an efficient pharmacological gene therapy for X-ALD is
      discussed.

PMID- 11342108
TI  - Cloning of new members of heat shock protein HSP101 gene family in wheat
      (Triticum aestivum (L.) Moench) inducible by heat, dehydration, and ABA(1).
AB  - We have cloned two cDNAs, TaHSP101B and TaHSP101C, encoding two heat stress
      inducible members of HSP101/ClpB family in bread wheat (Triticum aestivum (L.)
      Moench.). Proteins encoded by these cDNAs are highly similar at the primary
      sequence level and diverged from the previously reported TaHSP101 (designated
      TaHSP101A) both in the consensus ATP/GTP-binding region II and in the carboxy
      terminal region. The HSP101 gene was determined to be a single copy gene or a
      member of a small gene family in hexaploid wheat. Messages encoding HSP101
      proteins were inducible by heat stress treatments in both wheat leaves and roots.
      Accumulation of the TaHSP101C mRNA was less abundant than that of TaHSP101B mRNA.
      We are showing for the first time that in addition to heat stress, expression of
      HSP101 mRNAs in wheat leaves was induced by a 2-h dehydration and a treatment
      with 5x10(-5)M ABA, but not affected by chilling or wounding, indicating that
      HSP101 proteins may be involved in both heat and drought responses in wheat.

PMID- 11342109
TI  - Human Ca2+/calmodulin-dependent phosphodiesterase PDE1A: novel splice variants,
      their specific expression, genomic organization, and chromosomal localization.
AB  - We report here the identification of novel human PDE1A splice variants, their
      tissue distribution patterns, genomic structure, and chromosomal localization of
      the gene. We identified one N-terminus (N3) and one C-terminus (C3) by cDNA
      library screening and dbEST database search. These N- and C-termini, including
      the reported N-termini (N1 and N2) and C-termini (C1 and C2), combined to
      generate nine different PDE1A cDNAs. N1 and N2 are similar to the 5' ends of the
      bovine PDE1A proteins of 61 kDa and 59 kDa, respectively, and C1 and C2 are the
      3' ends of the reported human PDE1A variants. The results of PCR and Southern
      blot analysis show that nine PDE1A splice variants exhibit distinctive tissue
      distribution patterns by the difference of the N-terminus. PDE1As with N2 were
      widely expressed in various tissues, mainly in the kidney, liver, and pancreas.
      On the other hand, PDE1As with N1 and N3 were particularly expressed at a high
      level in the brain and testis, respectively. These findings suggest that the
      distinct expression patterns among PDE1A variants depend on the several promoters
      situated upstream of exons encoding 5' ends of the variants. The PDE1A gene spans
      over 120 kb of genomic DNA, and consists of at least 17 exons and 16 introns. The
      PDE1A gene was located on human chromosome 2q32 by fluorescent in situ
      hybridization analysis.

PMID- 11342110
TI  - Isolation and expression of a gene (CGR1) regulated during the yeast-hyphal
      transition in Candida albicans.
AB  - We used RNA fingerprinting of arbitrarily primed PCR to isolate genes upregulated
      during the yeast-hyphal transition in Candida albicans. The sequence and
      expression of one of these genes (CGR1, Candida growth regulation) are presented.
      Our results suggest that CGR1 expression is associated with a growth cessation of
      yeast cells, a prerequisite for germination in this organism.

PMID- 11342111
TI  - Isolation and characterization of a human thiamine pyrophosphokinase cDNA.
AB  - A human thiamine pyrophosphokinase cDNA clone (hTPK1) was isolated and sequenced.
      When the intact hTPK1 open reading frame was expressed as a histidine-tag fusion
      protein in Escherichia coli, marked enzyme activity was detected in the bacterial
      cells. The hTPK1 mRNA was widely expressed in various human tissues at a very low
      level, and the mRNA content in cultured fibroblasts was unaffected by the
      thiamine concentration of the medium. The chromosome localization of the hTPK1
      gene was assigned to 7q34.

PMID- 11342112
TI  - Identification and characterization of UBXD1, a novel UBX domain-containing gene
      on human chromosome 19p13, and its mouse ortholog.
AB  - We have identified a novel human gene, UBXD1, on chromosome 19p13, which encodes
      a putative protein containing a UBX domain. Expression analysis showed an
      enhanced presence in testis. We identified the corresponding orthologous genes in
      mouse and rat. The characterization of UBXD1 has allowed us to define a new class
      of UBX domain-containing proteins conserved during evolution.

PMID- 11342113
TI  - Cloning and characterization of the cDNA for a plastid sigma factor from the moss
      Physcomitrella patens.
AB  - We isolated a cDNA PpSig1 encoding a plastid sigma factor from the moss
      Physcomitrella patens. The PpSIG1 protein is composed of the conserved subdomains
      for recognition of -10 and -35 promoter elements, core complex binding and DNA
      melting. Southern blot analysis showed that the moss sig1 gene is likely a member
      of a small gene family. Transient expression assay using green fluorescent
      protein demonstrated that the N-terminal region of PpSIG1 functions as a
      chloroplast-targeting signal peptide. These observations suggest that multiple
      nuclear-encoded sigma factors regulate chloroplast gene expression in P. patens.

PMID- 11342114
TI  - A cDNA from human bone marrow encoding a protein exhibiting homology to the
      ATP1gamma1/PLM/MAT8 family of transmembrane proteins.
AB  - A cDNA clone, IWU-1, was cloned from human bone marrow. Its putative open reading
      frame encoded a protein of 115 amino acids with a calculated molecular mass of
      12.9 kDa. The deduced amino acid sequence exhibited high homology (>68%) to
      members of the ATP1gamma1/PLM/MAT8 family of single transmembrane proteins,
      primarily in the region containing the putative transmembrane domain. The
      sequence at the amino-terminal side exhibited high homology (>61%) to the
      cytoplasmic region of the angiotensin II type 1 receptors.

PMID- 11342115
TI  - Cloning and characterization of tissue inhibitor of metalloproteinase-3 (TIMP-3)
      from shark, Scyliorhinus torazame.
AB  - We cloned the full-length cDNA encoding TIMP-3 from the cartilage of cloudy
      dogfish, Scyliorhinus torazame. The entire open reading frame was composed of 645
      nucleotides and 214 residues including 12 conserved cysteines and asparagine-184,
      a putative site for N-linked sugars. It showed about 72% identity to those of
      other species based on the deduced amino acid sequence. The mRNA of shark TIMP-3
      were expressed abundantly in brain and cartilage tissues. To investigate the
      roles of shark TIMP-3, an expression vector was constructed and transfected into
      HT1080 human fibrosarcoma cells. Overexpression of shark TIMP-3 reduced the
      activity of MMP-2 in gelatin zymography. Through human Alu PCR based CAM assay,
      we also confirmed that shark TIMP-3 transfected HT1080 cells had less
      intravasation effects.

PMID- 11342116
TI  - Molecular cloning of PalBH, a mammalian homologue of the Aspergillus atypical
      calpain PalB.
AB  - A mammalian homologue of the Aspergillus atypical calpain PalB, PalBH, was
      identified and its cDNA sequences were determined in human and mouse. The PalBH
      mRNA was expressed nearly ubiquitously throughout mammalian tissues. When
      expressed in COS cells, PalBH was enriched in the nucleus, suggesting its role is
      distinct from that of conventional calpains.

PMID- 11342117
TI  - Molecular cloning of human thiamin pyrophosphokinase.
AB  - Thiamin pyrophosphokinase (TPK, EC 2.7.6.2) catalyses phosphorylation of thiamin
      to thiamin pyrophosphate, an active enzyme cofactor. Here we describe the cloning
      of complete human TPK1 cDNA from an adult liver library. Human TPK1 is 89%
      identical to murine TPK1 at the protein level. The gene maps to chromosome 7q34
      36, consists of at least eight exons, and spans a distance at least of 420 kb.
      The mRNA of human TPK1 is highly expressed in testis, small intestine and kidney
      with lesser but detectable expression in brain, liver, placenta and spleen. The
      availability of the human TPK1 gene will provide another useful tool for studying
      the role of this enzyme in human thiamin metabolism and deficiency state.

PMID- 11342118
TI  - Structure of a full-length cDNA clone for the pro-alpha1(V/XI) collagen chain of
      red seabream.
AB  - The cDNA of type V/XI collagen alpha1 (rsCOL) chain has been isolated from cells
      established from eyed-period eggs of red seabream, Pagrus major, and sequenced.
      The amino acid sequence deduced from red seabream alpha1(V/XI) chain resembles
      that of type XI collagen alpha1 chain. On the other hand, tissue distribution of
      rsCOL resembles that of type V collagen based on RT-PCR analysis. This is the
      first report of the cloning of the full-length cDNA of type V/XI collagen alpha1
      chain from fish.

PMID- 11342120
TI  - Commentary from the Editor.

PMID- 11342119
TI  - Cloning and characterization of a novel human leptin receptor overlapping
      transcript-like 1 gene (LEPROTL1).
AB  - A new full-length cDNA encoding a novel protein was isolated from our human fetal
      brain cDNA library. The cDNA consists of 2701 bp and has a putative open reading
      frame encoding 131 amino acids which possesses a JAK binding site (Pro(46)-Ile
      Pro(48) which is preceded by a cluster of hydrophobic residues) and is highly
      homologous to the leptin receptor gene-related protein (OB-RGRP). Northern blot
      analysis showed that this new gene is widely expressed in human tissues and
      radiation hybrid mapping placed the gene to human chromosome 8p21.1-8p21.2.

PMID- 11342121
TI  - Corrigendum to "Rhabdomyosarcoma rho(0) cells: isolation and characterization of
      mitochondrial DNA depleted cell line with 'muscle-like' properties"

PMID- 11342130
TI  - Crystal structure of 3,4-dihydroxy-2-butanone 4-phosphate synthase of riboflavin
      biosynthesis.
AB  - BACKGROUND: 3,4-Dihydroxy-2-butanone-4-phosphate synthase catalyzes a commitment
      step in the biosynthesis of riboflavin. On the enzyme, ribulose 5-phosphate is
      converted to 3,4-dihydroxy-2-butanone 4-phosphate and formate in steps involving
      enolization, ketonization, dehydration, skeleton rearrangement, and formate
      elimination. The enzyme is absent in humans and an attractive target for the
      discovery of antimicrobials for pathogens incapable of acquiring sufficient
      riboflavin from their hosts. The homodimer of 23 kDa subunits requires Mg(2+) for
      activity. RESULTS: The first three-dimensional structure of the enzyme was
      determined at 1.4 A resolution using the multiwavelength anomalous diffraction
      (MAD) method on Escherichia coli protein crystals containing gold. The protein
      consists of an alpha + beta fold having a complex linkage of beta strands.
      Intersubunit contacts are mediated by numerous hydrophobic interactions and three
      hydrogen bond networks. CONCLUSIONS: A proposed active site was identified on the
      basis of amino acid residues that are conserved among the enzyme from 19 species.
      There are two well-separated active sites per dimer, each of which comprise
      residues from both subunits. In addition to three arginines and two threonines,
      which may be used for recognizing the phosphate group of the substrate, the
      active site consists of three glutamates, two aspartates, two histidines, and a
      cysteine which may provide the means for general acid and base catalysis and for
      coordinating the Mg(2+) cofactor within the active site.

PMID- 11342129
TI  - Directed evolution of a new catalytic site in 2-keto-3-deoxy-6-phosphogluconate
      aldolase from Escherichia coli.
AB  - BACKGROUND: Aldolases are carbon bond-forming enzymes that have long been
      identified as useful tools for the organic chemist. However, their utility is
      limited in part by their narrow substrate utilization. Site-directed mutagenesis
      of various enzymes to alter their specificity has been performed for many years,
      typically without the desired effect. More recently directed evolution has been
      employed to engineer new activities onto existing scaffoldings. This approach
      allows random mutation of the gene and then selects for fitness to purpose those
      proteins with the desired activity. To date such approaches have furnished novel
      activities through multiple mutations of residues involved in recognition; in no
      instance has a key catalytic residue been altered while activity is retained.
      RESULTS: We report a double mutant of E. coli 2-keto-3-deoxy-6-phosphogluconate
      aldolase with reduced but measurable enzyme activity and a synthetically useful
      substrate profile. The mutant was identified from directed-evolution experiments.
      Modification of substrate specificity is achieved by altering the position of the
      active site lysine from one beta strand to a neighboring strand rather than by
      modification of the substrate recognition site. The new enzyme is different to
      all other existing aldolases with respect to the location of its active site to
      secondary structure. The new enzyme still displays enantiofacial discrimination
      during aldol addition. We have determined the crystal structure of the wild-type
      enzyme (by multiple wavelength methods) to 2.17 A and the double mutant enzyme to
      2.7 A resolution. CONCLUSIONS: These results suggest that the scope of directed
      evolution is substantially larger than previously envisioned in that it is
      possible to perturb the active site residues themselves as well as surrounding
      loops to alter specificity. The structure of the double mutant shows how
      catalytic competency is maintained despite spatial reorganization of the active
      site with respect to substrate.

PMID- 11342131
TI  - Structures of trihydroxynaphthalene reductase-fungicide complexes: implications
      for structure-based design and catalysis.
AB  - BACKGROUND: Trihydroxynaphthalene reductase catalyzes two intermediate steps in
      the fungal melanin biosynthetic pathway. The enzyme, a typical short-chain
      dehydrogenase, is the biochemical target of three commercial fungicides. The
      fungicides bind preferentially to the NADPH form of the enzyme. RESULTS: Three X
      ray structures of the Magnaporthe grisea enzyme complexed with NADPH and two
      commercial and one experimental fungicide were determined at 1.7 A (pyroquilon),
      2.0 A (2,3-dihydro-4-nitro-1H-inden-1-one, 1), and 2.1 A (phthalide) resolutions.
      The chemically distinct inhibitors occupy similar space within the enzyme's
      active site. The three inhibitors share hydrogen bonds with the side chain
      hydroxyls of Ser-164 and Tyr-178 via a carbonyl oxygen (pyroquilon and 1) or via
      a carbonyl oxygen and a ring oxygen (phthalide). Active site residues occupy
      similar positions among the three structures. A buried water molecule that is
      hydrogen bonded to the NZ nitrogen of Lys-182 in each of the three structures
      likely serves to stabilize the cationic form of the residue for participation in
      catalysis. CONCLUSIONS: The pro S hydrogen of NADPH (which is transferred as a
      hydride to the enzyme's naphthol substrates) is directed toward the carbonyl
      carbon of the inhibitors that mimic an intermediate along the reaction
      coordinate. Modeling tetrahydroxynaphthalene and trihydroxynaphthalene in the
      active site shows steric and electrostatic repulsion between the extra hydroxyl
      oxygen of the former substrate and the sulfur atom of Met-283 (the C-terminal
      residue), which accounts, in part, for the 4-fold greater substrate specificity
      for trihydroxynaphthalene over tetrahydroxynaphthalene.

PMID- 11342132
TI  - Structural basis for inhibition promiscuity of dual specific thrombin and factor
      Xa blood coagulation inhibitors.
AB  - BACKGROUND: A major current focus of pharmaceutical research is the development
      of selective inhibitors of the blood coagulation enzymes thrombin or factor Xa to
      be used as orally bioavailable anticoagulant drugs in thromboembolic disorders
      and in the prevention of venous and arterial thrombosis. Simultaneous direct
      inhibition of thrombin and factor Xa by synthetic proteinase inhibitors as a
      novel approach to antithrombotic therapy could result in potent anticoagulants
      with improved pharmacological properties. RESULTS: The binding mode of such dual
      specific inhibitors of thrombin and factor Xa was determined for the first time
      by comparative crystallography using human alpha-thrombin, human des-Gla (1--44)
      factor Xa and bovine trypsin as the ligand receptors. The benzamidine-based
      inhibitors utilize two different conformations for the interaction with thrombin
      and factor Xa/trypsin, which are evoked by the steric requirements of the
      topologically different S2 subsites of the enzymes. Compared to the unliganded
      forms of the proteinases, ligand binding induces conformational adjustments of
      thrombin and factor Xa active site residues indicative of a pronounced induced
      fit mechanism. CONCLUSION: The structural data reveal the molecular basis for a
      desired unselective inhibition of the two key components of the blood coagulation
      cascade. The 4-(1-methyl-benzimidazole-2-yl)-methylamino-benzamidine moieties of
      the inhibitors are able to fill both the small solvent accessible as well as the
      larger hydrophobic S2 pockets of factor Xa and thrombin, respectively. Distal
      fragments of the inhibitors are identified which fit into both the cation
      hole/aromatic box of factor Xa and the hydrophobic aryl binding site of thrombin.
      Thus, binding constants in the medium-to-low nanomolar range are obtained against
      both enzymes.

PMID- 11342133
TI  - Structure of the globular region of the prion protein Ure2 from the yeast
      Saccharomyces cerevisiae.
AB  - BACKGROUND: The [URE3] non-Mendelian element of the yeast S. cerevisiae is due to
      the propagation of a transmissible form of the protein Ure2. The infectivity of
      Ure2p is thought to originate from a conformational change of the normal form of
      the prion protein. This conformational change generates a form of Ure2p that
      assembles into amyloid fibrils. Hence, knowledge of the three-dimensional
      structure of prion proteins such as Ure2p should help in understanding the
      mechanism of amyloid formation associated with a number of neurodegenerative
      diseases. RESULTS: Here we report the three-dimensional crystal structure of the
      globular region of Ure2p (residues 95--354), also called the functional region,
      solved at 2.5 A resolution by the MAD method. The structure of Ure2p 95--354
      shows a two-domain protein forming a globular dimer. The N-terminal domain is
      composed of a central 4 strand beta sheet flanked by four alpha helices, two on
      each side. In contrast, the C-terminal domain is entirely alpha-helical. The fold
      of Ure2p 95--354 resembles that of the beta class glutathione S-transferases
      (GST), in line with a weak similarity in the amino acid sequence that exists
      between these proteins. Ure2p dimerizes as GST does and possesses a potential
      ligand binding site, although it lacks GST activity. CONCLUSIONS: The structure
      of the functional region of Ure2p is the first crystal structure of a prion
      protein. Structure comparisons between Ure2p 95--354 and GST identified a 32
      amino acid residues cap region in Ure2p exposed to the solvent. The cap region is
      highly flexible and may interact with the N-terminal region of the partner
      subunit in the dimer. The implication of this interaction in the assembly of
      Ure2p into amyloid fibrils is discussed.

PMID- 11342134
TI  - Phe217 regulates the transfer of allosteric information across the subunit
      interface of the RecA protein filament.
AB  - BACKGROUND: ATP-mediated cooperative assembly of a RecA nucleoprotein filament
      activates the protein for catalysis of DNA strand exchange. RecA is a classic
      allosterically regulated enzyme in that ATP binding results in a dramatic
      increase in ssDNA binding affinity. This increase in ssDNA binding affinity
      results almost exclusively from an ATP-mediated increase in cooperative filament
      assembly rather than an increase in the inherent affinity of monomeric RecA for
      DNA. Therefore, certain residues at the subunit interface must play an important
      role in transmitting allosteric information across the filament structure of
      RecA. RESULTS: Using electron microscopic analysis of RecA polymer formation in
      the absence of DNA, we show that while wild-type RecA undergoes a slight decrease
      in filament length in the presence of ATP, a Phe217Tyr substitution results in a
      dramatic ATP-induced increase in cooperative filament assembly. Biosensor DNA
      binding measurements reveal that the Phe217Tyr mutation increases ATP-mediated
      cooperative interaction between RecA subunits by more than 250-fold. CONCLUSIONS:
      These studies represent the first identification of a subunit interface residue
      in RecA (Phe217) that plays a critical role in regulating the flow of ATP
      mediated information throughout the protein filament structure. We propose a
      model by which conformational changes that occur upon ATP binding are propagated
      through the structure of a RecA monomer, resulting in the insertion of the Phe217
      side chain into a pocket in the neighboring subunit. This event serves as a key
      step in intersubunit communication leading to ATP-mediated cooperative filament
      assembly and high affinity binding to ssDNA.

PMID- 11342135
TI  - Annexin V--heparin oligosaccharide complex suggests heparan sulfate--mediated
      assembly on cell surfaces.
AB  - BACKGROUND: Annexin V, an abundant anticoagulant protein, has been proposed to
      exert its effects by self-assembling into highly ordered arrays on phospholipid
      membranes to form a protective anti-thrombotic shield at the cell surface. The
      protein exhibits very high-affinity calcium-dependent interactions with acidic
      phospholipid membranes, as well as specific binding to glycosaminoglycans (GAGs)
      such as heparin and heparan sulfate, a major component of cell surface
      proteoglycans. At present, there is no structural information to elucidate this
      interaction or the role it may play in annexin V function at the cell surface.
      RESULTS: We report the 1.9 A crystal structure of annexin V in complex with
      heparin-derived tetrasaccharides. This structure represents the first of a
      heparin oligosaccharide binding to a protein where calcium ions are essential for
      the interaction. Two distinct GAG binding sites are situated on opposite protein
      surfaces. Basic residues at each site were identified from the structure and site
      directed mutants were prepared. The heparin binding properties of these mutants
      were measured by surface plasmon resonance. The results confirm the roles of
      these mutated residues in heparin binding, and the kinetic and thermodynamic data
      define the functionally distinct character of each distal binding surface.
      CONCLUSION: The annexin V molecule, as it self-assembles into an organized array
      on the membrane surface, can bind the heparan sulfate components of cell surface
      proteoglycans. A novel model is presented in which proteoglycan heparan sulfate
      could assist in the localization of annexin V to the cell surface membrane and/or
      stabilization of the entire molecular assembly to promote anticoagulation.

PMID- 11342136
TI  - Crystal structure of phosphoserine phosphatase from Methanococcus jannaschii, a
      hyperthermophile, at 1.8 A resolution.
AB  - BACKGROUND: D-Serine is a co-agonist of the N-methyl-D-aspartate subtype of
      glutamate receptors, a major neurotransmitter receptor family in mammalian
      nervous systems. D-Serine is converted from L-serine, 90% of which is the product
      of the enzyme phosphoserine phosphatase (PSP). PSP from M. jannaschii (MJ) shares
      significant sequence homology with human PSP. PSPs and P-type ATPases are members
      of the haloacid dehalogenase (HAD)-like hydrolase family, and all members share
      three conserved sequence motifs. PSP and P-type ATPases utilize a common
      mechanism that involves Mg(2+)-dependent phosphorylation and
      autodephosphorylation at an aspartyl side chain in the active site. The strong
      resemblance in sequence and mechanism implies structural similarity among these
      enzymes. RESULTS: The PSP crystal structure resembles the NAD(P) binding Rossmann
      fold with a large insertion of a four-helix-bundle domain and a beta hairpin.
      Three known conserved sequence motifs are arranged next to each other in space
      and outline the active site. A phosphate and a magnesium ion are bound to the
      active site. The active site is within a closed environment between the core
      alpha/beta domain and the four-helix-bundle domain. CONCLUSIONS: The crystal
      structure of MJ PSP was determined at 1.8 A resolution. Critical residues were
      assigned based on the active site structure and ligand binding geometry. The PSP
      structure is in a closed conformation that may resemble the phosphoserine bound
      state or the state after autodephosphorylation. Compared to a P-type ATPase
      (Ca(2+)-ATPase) structure, which is in an open state, this PSP structure appears
      also to be a good model for the closed conformation of P-type ATPase.

PMID- 11342137
TI  - Molecular basis for regulatory subunit diversity in cAMP-dependent protein
      kinase: crystal structure of the type II beta regulatory subunit.
AB  - BACKGROUND: Cyclic AMP binding domains possess common structural features yet are
      diversely coupled to different signaling modules. Each cAMP binding domain
      receives and transmits a cAMP signal; however, the signaling networks differ even
      within the same family of regulatory proteins as evidenced by the long-standing
      biochemical and physiological differences between type I and type II regulatory
      subunits of cAMP-dependent protein kinase. RESULTS: We report the first type II
      regulatory subunit crystal structure, which we determined to 2.45 A resolution
      and refined to an R factor of 0.176 with a free R factor of 0.198. This new
      structure of the type II beta regulatory subunit of cAMP-dependent protein kinase
      demonstrates that the relative orientations of the two tandem cAMP binding
      domains are very different in the type II beta as compared to the type I alpha
      regulatory subunit. Each structural unit for binding cAMP contains the highly
      conserved phosphate binding cassette that can be considered the "signature" motif
      of cAMP binding domains. This motif is coupled to nonconserved regions that link
      the cAMP signal to diverse structural and functional modules. CONCLUSIONS: Both
      the diversity and similarity of cAMP binding sites are demonstrated by this new
      type II regulatory subunit structure. The structure represents an intramolecular
      paradigm for the cooperative triad that links two cAMP binding sites through a
      domain interface to the catalytic subunit of cAMP-dependent protein kinase. The
      domain interface surface is created by the binding of only one cAMP molecule and
      is enabled by amino acid sequence variability within the peptide chain that
      tethers the two domains together.

PMID- 11342140
TI  - Exploring the domain structure of modular nonribosomal peptide synthetases.
AB  - Recently, considerable insight has been gained into the modular organization of
      nonribosomal peptide synthetases (NRPS). The three-dimensional structures of
      domains associated with substrate adenylation and covalent binding have been
      solved as well as the structure of a priming enzyme required for the post
      translational modification of NRPS. Taken together, these studies will help us to
      understand the architecture of these mega-enzymes.

PMID- 11342141
TI  - Selenomethionine incorporation in Saccharomyces cerevisiae RNA polymerase II.
AB  - A protocol for the incorporation of SeMet into yeast proteins is described.
      Incorporation at a level of about 50% suffices for the location of Se sites in an
      anomalous difference Fourier map of the 0.5 MDa yeast RNA polymerase II. This
      shows the utility of the approach as an aid in the model-building of large
      protein complexes.

PMID- 11342142
TI  - Potassium and sodium ions in a potassium channel studied by molecular dynamics
      simulations.
AB  - We have performed simulations of both a single potassium ion and a single sodium
      ion within the pore of the bacterial potassium channel KcsA. For both ions there
      is a dehydration energy barrier at the cytoplasmic mouth suggesting that the
      crystal structure is a closed conformation of the channel. There is a potential
      energy barrier for a sodium ion in the selectivity filter that is not seen for
      potassium. Radial distribution functions for both ions with the carbonyl oxygens
      of the selectivity filter indicate that sodium may interact more tightly with the
      filter than does potassium. This suggests that the key to the ion selectivity of
      KcsA is the greater dehydration energy of Na(+) ions, and helps to explain the
      block of KcsA by internal Na(+) ions.

PMID- 11342143
TI  - Evidence for the transport of neutral as well as cationic amino acids by ATA3, a
      novel and liver-specific subtype of amino acid transport system A.
AB  - We report here on the cloning and functional characterization of the third
      subtype of amino acid transport system A, designated ATA3 (amino acid transporter
      A3), from a human liver cell line. This transporter consists of 547 amino acids
      and is structurally related to the members of the glutamine transporter family.
      The human ATA3 (hATA3) exhibits 88% identity in amino acid sequence with rat
      ATA3. The gene coding for hATA3 contains 16 exons and is located on human
      chromosome 12q13. It is expressed almost exclusively in the liver. hATA3 mediates
      the transport of neutral amino acids including alpha-(methylamino)isobutyric acid
      (MeAIB), the model substrate for system A, in a Na(+)-coupled manner and the
      transport of cationic amino acids in a Na(+)-independent manner. The affinity of
      hATA3 for cationic amino acids is higher than for neutral amino acids. The
      transport function of hATA3 is thus similar to that of system y(+)L. The ability
      of hATA3 to transport cationic amino acids with high affinity is unique among the
      members of the glutamine transporter family. hATA1 and hATA2, the other two known
      members of the system A subfamily, show little affinity toward cationic amino
      acids. hATA3 also differs from hATA1 and hATA2 in exhibiting low affinity for
      MeAIB. Since liver does not express any of the previously known high-affinity
      cationic amino acid transporters, ATA3 is likely to provide the major route for
      the uptake of arginine in this tissue.

PMID- 11342144
TI  - Cholesterol regulates membrane binding and aggregation by annexin 2 at
      submicromolar Ca(2+) concentration.
AB  - Annexin 2 is a member of the annexin family which has been implicated in calcium
      regulated exocytosis. This contention is largely based on Ca(2+)-dependent
      binding of the protein to anionic phospholipids. However, annexin 2 was shown to
      be associated with chromaffin granules in the presence of EGTA. A fraction of
      this bound annexin 2 was released by methyl-beta-cyclodextrin, a reagent which
      depletes cholesterol from membranes. Restoration of the cholesterol content of
      chromaffin granule membranes with cholesterol/methyl-beta-cyclodextrin complexes
      restored the Ca(2+)-independent binding of annexin 2. The binding of both,
      monomeric and tetrameric forms of annexin 2 was also tested on liposomes of
      different composition. In the absence of Ca(2+), annexin 2, especially in its
      tetrameric form, bound to liposomes containing phosphatidylserine, and the
      addition of cholesterol to these liposomes increased the binding. Consistent with
      this observation, liposomes containing phosphatidylserine and cholesterol were
      aggregated by the tetrameric form of annexin 2 at submicromolar Ca(2+)
      concentrations. These results indicate that the lipid composition of membranes,
      and especially their cholesterol content, is important in the control of the
      subcellular localization of annexin 2 in resting cells, at low Ca(2+)
      concentration. Annexin 2 might be associated with membrane domains enriched in
      phosphatidylserine and cholesterol.

PMID- 11342145
TI  - Activation of an ATP-dependent K(+) conductance in Xenopus oocytes by expression
      of adenylate kinase cloned from renal proximal tubules.
AB  - In rabbit proximal convoluted tubules, an ATP-sensitive K(+) (K(ATP)) channel has
      been shown to be involved in membrane cross-talk, i.e. the coupling (most likely
      mediated through intracellular ATP) between transepithelial Na(+) transport and
      basolateral K(+) conductance. This K(+) conductance is inhibited by taurine. We
      sought to isolate this K(+) channel by expression cloning in Xenopus oocytes.
      Injection of renal cortex mRNA into oocytes induced a K(+) conductance, largely
      inhibited by extracellular Ba(2+) and intracellular taurine. Using this
      functional test, we isolated from our proximal tubule cDNA library a unique
      clone, which induced a large K(+) current which was Ba(2+)-, taurine- and
      glibenclamide-sensitive. Surprisingly, this clone is not a K(+) channel but an
      adenylate kinase protein (AK3), known to convert NTP+AMP into NDP+ADP (N could be
      G, I or A). AK3 expression resulted in a large ATP decrease and activation of the
      whole-cell currents including a previously unknown, endogenous K(+) current. To
      verify whether ATP decrease was responsible for the current activation, we
      demonstrated that inhibition of glycolysis greatly reduces oocyte ATP levels and
      increases an inwardly rectifying K(+) current. The possible involvement of AK in
      the K(ATP) channel's regulation provides a means of explaining their observed
      activity in cytosolic environments characterized by high ATP concentrations.

PMID- 11342147
TI  - Selective protein interactions with phosphatidylserine containing liposomes alter
      the steric stabilization properties of poly(ethylene glycol).
AB  - Incorporation of 5 mol% poly(ethylene glycol)-conjugated lipids (PEG-lipids) has
      been shown to extend the circulation longevity of neutral liposomes due to steric
      repulsion of PEG at the membrane surface. The effects of PEG-lipids on protein
      interactions with biologically reactive membranes were examined using
      phosphatidylserine (PS) containing liposomes as the model. Incorporating 15 mol%
      1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE)-PEG 2000 into PS liposomes
      resulted in circulation lifetimes comparable to that obtained with neutral
      liposomes containing 5 mol% DSPE-PEG 2000. These results suggested that 15 mol%
      DSPE-PEG 2000 may be effective in protecting PS liposomes from the high affinity,
      PS-mediated binding of plasma proteins. This was determined by monitoring the
      effects of PEG-lipids on calcium-mediated blood coagulation protein interactions
      with PS liposomes. Prothrombin binding and procoagulant activity of PS liposomes
      could be inhibited >80% when 15 mol% DSPE-PEG 2000 was used. These results are
      consistent with PS on membrane surfaces forming transient nucleation sites for
      protein binding that may result in lateral exclusion of PEG-lipids incorporated
      at <10 mol%. These nucleation sites may be inaccessible when PEG-lipids are
      present at elevated levels where they adopt a highly compressed brush
      conformation. This suggests that liposomes with reactive groups and PEG-lipids
      may be appropriately designed to impart selectivity to protein interactions with
      membrane surfaces.

PMID- 11342146
TI  - Anti-MUC-1 immunoliposomal doxorubicin in the treatment of murine models of
      metastatic breast cancer.
AB  - The fate of breast cancer patients is dependent upon elimination or control of
      metastases. We studied the effect of antibody-targeted liposomes containing
      entrapped doxorubicin (DXR) on development of tumours in two models of breast
      cancer, pseudometastatic and metastatic, in mice. The former used the mouse
      mammary carcinoma cell line GZHI, which expresses the human MUC-1 gene (L. Ding,
      E.N. Lalani, M. Reddish, R. Koganty, T. Wong, J. Samuel, M.B. Yacyshyn, A.
      Meikle, P.Y.S. Fung, J. Taylor-Papadimitriou, B.M. Longenecker, Cancer Immunol.
      Immunother. 36 (1993) 9--17). GZHI cells seed into the lungs of Balb/c mice
      following intravenous injection. The latter used the 4T1-MUC1 cell line, a MUC-1
      transfectant of the mouse mammary carcinoma cell line 4T1, which metastasizes
      from a primary mammary fatpad (mfp) implant to the lungs (C.J. Aslakson, F.R.
      Miller, Cancer Res. 52 (1992) 1399--1405). B27.29, a monoclonal antibody against
      the MUC-1 antigen, was used to target sterically stabilized immunoliposomes
      (SIL[B27.29]) to tumour cells. In vitro, SIL[B27.29] showed high specific binding
      to both GZHI and 4T1-MUC1 cells. The IC(50) of DXR-loaded SIL[B27.29] was similar
      to that of free drug for GZHI cells. In the pseudometastatic model, mice treated
      with a single injection of 6 mg DXR/kg in DXR-SIL[B27.29] at 24 h after cell
      implantation had longer survival times than those injected with non-targeted
      liposomal drug. In the metastatic model, severe combined immune deficiency mice
      given weekly injectionsx3 of 2.5 mg DXR/kg encapsulated in either targeted or non
      targeted liposomes were almost equally effective in slowing growth of the primary
      tumour and reducing development of lung tumours. Surgical removal of the primary
      tumour from mfp, followed by various chemotherapy regimens, was attempted, but
      removal of the primary tumour was generally incomplete; tumour regrowth occurred
      and metastases developed in the lungs in all treatment groups. DXR-SL reduced the
      occurrence of regrowth of the primary tumour, whereas neither targeted liposomal
      drug or free drug prevented regrowth. We conclude that monoclonal antibody
      targeted liposomal DXR is effective in treating early lesions in both the
      pseudometastatic and metastatic models, but limitations to the access of the
      targeted liposomes to tumour cells in the primary tumour compromised their
      therapeutic efficacy in treating the more advanced lesions.

PMID- 11342148
TI  - The thermotropic phase behavior of cationic lipids: calorimetric, infrared
      spectroscopic and X-ray diffraction studies of lipid bilayer membranes composed
      of 1,2-di-O-myristoyl-3-N,N,N-trimethylaminopropane (DM-TAP).
AB  - The thermotropic phase behavior of lipid bilayer model membranes composed of the
      cationic lipid 1,2-di-O-myristoyl-3-N,N,N-trimethylaminopropane (DM-TAP) was
      examined by differential scanning calorimetry, infrared spectroscopy and X-ray
      diffraction. Aqueous dispersions of this lipid exhibit a highly energetic
      endothermic transition at 38.4 degrees C upon heating and two exothermic
      transitions between 20 and 30 degrees C upon cooling. These transitions are
      accompanied by enthalpy changes that are considerably greater than normally
      observed with typical gel/liquid--crystalline phase transitions and have been
      assigned to interconversions between lamellar crystalline and lamellar liquid-
      crystalline forms of this lipid. Both infrared spectroscopy and X-ray diffraction
      indicate that the lamellar crystalline phase is a highly ordered, substantially
      dehydrated structure in which the hydrocarbon chains are essentially immobilized
      in a distorted orthorhombic subcell. Upon heating to temperatures near 38.4
      degrees C, this structure converts to a liquid-crystalline phase in which there
      is excessive swelling of the aqueous interlamellar spaces owing to charge
      repulsion between, and undulations of, the positively charged lipid surfaces. The
      polar/apolar interfaces of liquid--crystalline DM-TAP bilayers are not as well
      hydrated as those formed by other classes of phospho- and glycolipids. Such
      differences are attributed to the relatively small size of the polar headgroup
      and its limited capacity for interaction with moieties in the bilayer
      polar/apolar interface.

PMID- 11342149
TI  - Cholesterol attenuates the interaction of the antimicrobial peptide gramicidin S
      with phospholipid bilayer membranes.
AB  - We have investigated the effect of the presence of 25 mol percent cholesterol on
      the interactions of the antimicrobial peptide gramicidin S (GS) with
      phosphatidylcholine and phosphatidylethanolamine model membrane systems using a
      variety of methods. Our circular dichroism spectroscopic measurements indicate
      that the incorporation of cholesterol into egg phosphatidylcholine vesicles has
      no significant effect on the conformation of the GS molecule but that this
      peptide resides in a range of intermediate polarity as compared to aqueous
      solution or an organic solvent. Our Fourier transform infrared spectroscopic
      measurements confirm these findings and demonstrate that in both cholesterol
      containing and cholesterol-free dimyristoylphosphatidylcholine liquid-crystalline
      bilayers, GS is located in a region of intermediate polarity at the polar-
      nonpolar interfacial region of the lipid bilayer. However, GS appears to be
      located in a more polar environment nearer the bilayer surface when cholesterol
      is present. Our (31)P-nuclear magnetic resonance studies demonstrate that the
      presence of cholesterol markedly reduces the tendency of GS to induce the
      formation of inverted nonlamellar phases in model membranes composed of an
      unsaturated phosphatidylethanolamine. Finally, fluorescence dye leakage
      experiments indicate that cholesterol inhibits the GS-induced permeabilization of
      phosphatidylcholine vesicles. Thus in all respects the presence of cholesterol
      attenuates but does not abolish the interactions of GS with, and the
      characteristic effects of GS on, phospholipid bilayers. These findings may
      explain why it is more potent at disrupting cholesterol-free bacterial than
      cholesterol-containing eukaryotic membranes while nevertheless disrupting the
      integrity of the latter at higher peptide concentrations. This additional example
      of the lipid specificity of GS may aid in the rational design of GS analogs with
      increased antibacterial but reduced hemolytic activities.

PMID- 11342150
TI  - Local anesthetic-induced microscopic and mesoscopic effects in micelles. A
      fluorescence, spin label and SAXS study. Single angle X-ray scattering.
AB  - The interaction of the local anesthetic tetracaine (TTC) with anionic sodium
      lauryl sulfate (SLS) and zwitterionic 3-(N-hexadecyl-N,N
      dimethylammonio)propanesulfonate (HPS) micelles was investigated by fluorescence,
      spin labeling EPR and small angle X-ray scattering (SAXS). Fluorescence pH
      titrations allowed the choice of adequate pHs for the EPR and SAXS experiments,
      where either charged or uncharged TTC would be present. The data also indicated
      that the anesthetic is located in a less polar environment than its charged
      counterpart in both micellar systems. EPR spectra evidenced that both anesthetic
      forms increased molecular organization within the SLS micelle, the cationic form
      exerting a more pronounced effect. The SAXS data showed that protonated TTC
      causes an increase in the SLS polar shell thickness, hydration number, and
      aggregation number, whereas the micellar features are not altered upon
      incorporation of the uncharged drug. The combined results suggest that the
      electrostatic interaction between charged TTC and SLS, and the intercalation of
      the drug in the micellar polar region induce a change in molecular packing with a
      decrease in the mean cross-sectional area, not observed when the neutral drug
      sinks more deeply into the micellar hydrophobic domain. In the case of HPS
      micelles, the EPR spectral changes were small for the charged anesthetic and the
      SAXS data did not evidence any change in micellar structure, suggesting that this
      species protrudes more into the aqueous phase due to the lack of electrostatic
      attractive forces in this system.

PMID- 11342151
TI  - Surface activity and film formation from the surface associated material of
      artificial surfactant preparations.
AB  - Surfactant proteins B and C (SP-B and SP-C) are present in natural derived
      surfactant preparations used for treatment of respiratory distress syndrome.
      Herein the surface activity of an SP-C analogue (SP-C(LKS)), a hybrid peptide
      between SP-C and bacteriorhodopsin (SP-C/BR) and a model peptide (KL(4)) was
      studied with a captive bubble surfactometer (CBS). The peptides were mixed with
      either 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC)/phosphatidylglycerol
      (PG) (7:3, by weight) or DPPC/PG/palmitic acid (68:22:9, by weight) at a
      concentration of 1 mg/ml in HEPES buffer, pH 6.9 and a polypeptide/lipid weight
      ratio of 0.02--0.03. In some lipid/peptide preparations also 2% of SP-B was
      included. Adsorption, monitored as surface tension vs. time for 10 min after
      bubble formation did not show discernible differences for the whole set of
      preparations. Equilibrium surface tensions of approximately 25 mN/m were reached
      after 5--10 min for all preparations, although those with SP-C/BR appeared not to
      reach end point of adsorption within 10 min. Area compression needed to reach
      minimum surface tension of 0.5--2.0 mN/m was least for the KL(4) preparation,
      about 13% in the first cycle. 3% SP-C(LKS) in DPPC:PG (7:3, by weight) reached
      minimum surface tension upon 27% compression in the first cycle. If DPPC:PG:PA
      (68:22:9, by weight) was used instead only 16% area compression was needed and
      14% if also 2% SP-B was included. 3% SP-C(LKS) in DPPC:PG (7:3, by weight)+2% SP
      B needed 34% compression to reach minimum surface tension. The replenishment of
      material from a surface associated surfactant reservoir was estimated with
      subphase depletion experiments. With the 2% KL(4) preparation incorporation of
      excess material took place at a surface tension of 25--35 mN/m during stepwise
      bubble expansion and excess material equivalent to 4.3 monolayers was found. When
      2% SP-B was added to 3% SP-C(LKS) in DPPC:PG (7:3, by weight) the number of
      excess monolayers increased from 1.5 to 3.6 and the incorporation took place at
      30--40 mN/m. When SP-B was added to 3% SP-C(LKS) in DPPC:PG:PA (68:22:9, by
      weight) the number of excess monolayers increased from 0.5 to 3.4 and
      incorporation took place at 40--50 mN/m. With 2% SP-C/BR incorporation took place
      at 40--45 mN/m, frequent instability clicks were observed and excess material of
      approximately 1.1 monolayer was estimated.

PMID- 11342152
TI  - Differential regulation of Na(+),K(+)-ATPase and the Na(+)-coupled glucose
      transporter in hypertensive rat kidney.
AB  - Several Na(+) transporters are functionally abnormal in the hypertensive rat.
      Here, we examined the effects of a high-salt load on renal Na(+),K(+)-ATPase and
      the sodium-coupled glucose transporter (SGLT1) in Dahl salt-resistant (DR) and
      salt-sensitive (DS) rats. The protein levels of Na(+),K(+)-ATPase and SGLT1 in
      the DS rat were the same as those in the DR rat, and were not affected by the
      high-salt load. In the DS rat, a high-salt load decreased Na(+),K(+)-ATPase
      activity, and this decrease coincided with a decrease in the apparent Mechaelis
      constant (K(m)) for ATP, but not with a change of maximum velocity (V(max)). On
      the contrary, a high-salt load increased SGLT1 activity in the DS rat, which
      coincided with an increase in the V(max) for alpha-methyl glucopyranoside. The
      protein level of phosphorylated tyrosine residues in Na(+),K(+)-ATPase was
      decreased by the high-salt load in the DS rat. The amount of phosphorylated
      serine was not affected by the high-salt load in DR rats, and could not be
      detected in DS rats. On the other hand, the amount of phosphorylated serine
      residues in SGLT1 was increased by the high-salt load. However, the
      phosphorylated tyrosine was the same for all samples. Therefore, we concluded
      that the high-salt load changes the protein kinase levels in DS rats, and that
      the regulation of Na(+),K(+)-ATPase and SGLT1 activity occurs via protein
      phosphorylation.

PMID- 11342153
TI  - A photophysical study of the polyene antibiotic filipin. Self-aggregation and
      filipin--ergosterol interaction.
AB  - Filipin, a macrolide polyene antibiotic, is known to interact selectively with
      ergosterol, a constituent of fungi membranes. In this work, the fluorescence
      resonance energy transfer (FRET) between a fluorescent analog of ergosterol,
      dehydroergosterol (DHE), and filipin was measured in small unilamellar vesicles
      of dipalmitoylphosphatidylcholine at 25 degrees C. The time-resolved FRET results
      were rationalized in the framework of the mean concentration model, and were
      complemented with steady-state fluorescence intensity, anisotropy and absorption
      measurements. The results point to the formation of both DHE--filipin aggregates
      (evidence from static quenching of DHE fluorescence by filipin) and filipin-
      filipin aggregates (evidence from: (i) the FRET acceptor concentration
      distributions; (ii) spectral changes of filipin absorption in the vesicles, the
      excitonic interaction suggesting a stack arrangement; (iii) filipin fluorescence
      self-quenching), even in presence of DHE and low antibiotic mole fractions (<1
      mol%). These results point out that apparently contradictory biochemical models
      for the action of filipin (some based on the presence of sterols, others not) can
      be equally valid. Moreover, since results (ii) and (iii) are also observed when a
      sterol is present, both models of action can actually coexist in membranes with a
      low sterol content.

PMID- 11342154
TI  - Kinetic analysis of the initial steps involved in lipoplex--cell interactions:
      effect of various factors that influence transfection activity.
AB  - We investigated the mode of interaction of lipoplexes (DOTAP:DOPE/DNA) with HeLa
      cells, focusing on the analysis of the initial steps involved in the process of
      gene delivery. We evaluated the effect of different factors, namely the
      stoichiometry of cationic lipids and DNA, the presence of serum in the cell
      culture medium, and the incorporation of the ligand transferrin into the
      lipoplexes, on the extent of binding, association and fusion (lipid mixing) of
      the lipoplexes with the cells. Parallel experiments were performed upon cell
      treatment with inhibitors of endocytosis. Our results indicate that a decrease of
      the net charge of the complexes (upon addition of DNA) generally leads to a
      decrease in the extent of binding, cell association and fusion, except for the
      neutral complexes. Association of transferrin to the lipoplexes resulted in a
      significant enhancement of the interaction processes referred to above, which
      correlates well with the promotion of transfection observed under the same
      conditions. Besides triggering internalization of the complexes, transferrin was
      also shown to mediate fusion with the endosomal membrane. The extent of fusion of
      this type of complexes was reduced upon their incubation with cells in the
      presence of serum, suggesting that serum components limit the transferrin
      fusogenic properties. Results were analyzed by using a theoretical model which
      allowed to estimate the kinetic parameters involved in lipoplex--cell
      interactions. The deduced fusion and endocytosis rate constants are discussed and
      compared with those obtained for other biological systems. From the kinetic
      studies we found a twofold enhancement of the fusion rate constant (f) for the
      ternary lipoplexes. We also concluded that HeLa cells yield a relatively low rate
      of endocytosis. Overall, our results estimate the relative contribution of fusion
      of lipoplexes with the plasma membrane, endocytosis and fusion with the endosomal
      membrane to their interactions with cells, this information being of crucial
      importance for the development of gene therapy strategies.

PMID- 11342155
TI  - Efficient encapsulation of antisense oligonucleotides in lipid vesicles using
      ionizable aminolipids: formation of novel small multilamellar vesicle structures.
AB  - Typical methods used for encapsulating antisense oligodeoxynucleotides (ODN) and
      plasmid DNA in lipid vesicles result in very low encapsulation efficiencies or
      employ cationic lipids that exhibit unfavorable pharmacokinetic and toxicity
      characteristics when administered intravenously. In this study, we describe and
      characterize a novel formulation process that utilizes an ionizable aminolipid
      (1,2-dioleoyl-3-dimethylammonium propane, DODAP) and an ethanol-containing buffer
      system for encapsulating large quantities (0.15--0.25 g ODN/g lipid) of
      polyanionic ODN in lipid vesicles. This process requires the presence of up to
      40% ethanol (v/v) and initial formulation at acidic pH values where the DODAP is
      positively charged. In addition, the presence of a poly(ethylene glycol)-lipid
      was required during the formulation process to prevent aggregation. The
      'stabilized antisense-lipid particles' (SALP) formed are stable on adjustment of
      the external pH to neutral pH values and the formulation process allows
      encapsulation efficiencies of up to 70%. ODN encapsulation was confirmed by
      nuclease protection assays and (31)P NMR measurements. Cryo-electron microscopy
      indicated that the final particles consisted of a mixed population of unilamellar
      and small multilamellar vesicles (80--140 nm diameter), the relative proportion
      of which was dependent on the initial ODN to lipid ratio. Finally, SALP exhibited
      significantly enhanced circulation lifetimes in mice relative to free antisense
      ODN, cationic lipid/ODN complexes and SALP prepared with quaternary aminolipids.
      Given the small particle sizes and improved encapsulation efficiency, ODN to
      lipid ratios, and circulation times of this formulation compared to others, we
      believe SALP represent a viable candidate for systemic applications involving
      nucleic acid therapeutics.

PMID- 11342156
TI  - Interaction of ceramides with phosphatidylcholine, sphingomyelin and
      sphingomyelin/cholesterol bilayers.
AB  - Ceramides (Cers) may exert their biological activity through changes in membrane
      structure and organization. To understand this mechanism, the effect of Cer on
      the biophysical properties of phosphatidylcholine, sphingomyelin (SM) and
      SM/cholesterol bilayers was determined using fluorescence probe techniques. The
      Cers were bovine brain Cer and synthetic Cers that contained a single acyl chain
      species. The phospholipids were 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine
      (POPC) and 1,2-dipalmitoyl-sn-glyero-3-phosphocholine (DPPC) and bovine brain,
      egg yolk and bovine erythrocyte SM. The addition of Cer to POPC and DPPC bilayers
      that were in the liquid-crystalline phase resulted in a linear increase in acyl
      chain order and decrease in membrane polarity. The addition of Cer to DPPC and SM
      bilayers also resulted in a linear increase in the gel to liquid-crystalline
      phase transition temperature (T(M)). The magnitude of the change was dependent
      upon Cer lipid composition and was much higher in SM bilayers than DPPC bilayers.
      The addition of 33 mol% cholesterol essentially eliminated the thermal transition
      of SM and SM/Cer bilayers. However, there is still a linear increase in acyl
      chain order induced by the addition of Cer. The results are interpreted as the
      formation of DPPC/Cer and SM/Cer lipid complexes. SM/Cer lipid complexes have
      higher T(M)s than the corresponding SM because the addition of Cer reduces the
      repulsion between the bulky headgroup and allows closer packing of the acyl
      chains. The biophysical properties of a SM/Cer-rich bilayer are dependent upon
      the amount of cholesterol present. In a cholesterol-poor membrane, a
      sphingomyelinase could catalyze the isothermal conversion of a liquid-crystalline
      SM bilayer to a gel phase SM/Cer complex at physiological temperature.

PMID- 11342157
TI  - Physico-chemical analysis of lipid A fractions of lipopolysaccharide from Erwinia
      carotovora in relation to bioactivity.
AB  - Highly purified bisphosphoryl, monophosphoryl and dephosphoryl lipids A from
      Erwinia carotovora with different acylation patterns were characterized physico
      chemically. Applying matrix assisted laser desorption/ionization mass
      spectrometry, the purity of the lipid A fractions was determined, and from
      monolayer measurements the molecular space requirement was estimated. Fourier
      transform infrared spectroscopy allowed the elucidation of the gel to liquid
      crystalline phase transition of the acyl chains as well as the determination of
      the tilt angle of the diglucosamine backbone with respect to the acyl chain
      direction applying dichroitic measurements with attenuated total reflectance.
      With synchrotron radiation small-angle X-ray diffraction the supramolecular
      aggregate structure was determined, and with fluorescence resonance energy
      transfer spectroscopy the lipopolysaccharide binding protein induced
      intercalation of lipid A into a phospholipid matrix corresponding to that of the
      macrophage membrane was investigated. From the results, a clear dependence of the
      physico-chemical parameters on the particular lipid A structure can be followed.
      Furthermore, these parameters correlate well with the biological activities of
      the various lipids A as deduced from their ability to induce biological activity
      (Limulus assay and cytokine induction in mononuclear cells). These results
      contribute to a closer interpretation of the physico-chemical prerequisites for
      endotoxic activity as found for enterobacterial lipid A.

PMID- 11342158
TI  - Enhancement of gene delivery by an analogue of alpha-MSH in a receptor
      independent fashion.
AB  - In order to transfect melanoma specifically by receptor-mediated endocytosis we
      prepared dioctadecyl aminoglycylspermine (lipospermine)--DNA complexes with
      [Nle(4),D-Phe(7)]-alpha-MSH(4--10), a pseudo-peptide analogue of alpha-melanocyte
      stimulating hormone (alpha-MSH) linked to a thiol-reactive phospholipid. With
      these complexes we obtained an up to 70-fold increase of transfection with B16-F1
      melanoma cells. However when B16-G4F, an alpha-MSH receptor negative melanoma
      cell line was transfected, an up to 700-fold increased transfection efficiency
      was observed. The peptide hormone analogue was equally efficient when it was only
      mixed with lipospermine--DNA complexes without covalent coupling. In addition to
      melanoma cells we also obtained up to 30-fold increased transfection with BN
      cells (embryonic liver cells). Our data show that an alpha-MSH analogue increased
      transfection independently of the MSH receptor expression but reaches
      efficiencies approaching those obtained with peptides derived from viral fusion
      proteins. The absence of targeting of constructs containing [Nle(4),D-Phe(7)]
      alpha-MSH(4-10) can probably be attributed due to the relatively modest number of
      MSH receptors at the surface of melanoma. We suggest, however, that the peptide
      hormone analogue used in this study has membrane-active properties and could be
      of interest as helper agent to enhance non-viral gene delivery presumably by
      endosomal-destabilizing properties.

PMID- 11342159
TI  - Ion channels formed by transcription factors recognize consensus DNA sequences.
AB  - Transcription factors (TFs) are proteins which bind to specific DNA sequences and
      thus participate in the regulation of the initiation of transcription. We report
      in this communication our observations that several of these proteins interact
      with lipid membranes and form ion-permeable channels. For each of the TFs that we
      studied, the single channel conductance was distinctively different, i.e. each TF
      had its own electrical signature. More importantly, we show for the first time
      that addition of cognate double-stranded DNA sequences leads to a specific
      response: an increase in the conductance of the TF-containing membrane.
      Strikingly, the effect of cognate DNA was observed when it was added to the trans
      side of the membrane (opposite to where the TF was added), strongly suggesting
      that the TFs span the membrane and that the DNA-binding domain is trans
      accessible. Alterations in the primary structure of the TF factors in their basic
      and DNA-binding regions change the characteristics of the conductance of the
      protein-containing membranes as well as the response to DNA addition, reinforcing
      the notion that the changes we measure are due to specific interactions.

PMID- 11342160
TI  - The effect of ethanol on the phase transition temperature and the phase structure
      of monounsaturated phosphatidylcholines.
AB  - Previous studies from our laboratories have delineated the relationship between
      the acyl chain asymmetry of mixed-chain phosphatidylcholines, C(X):C(Y)PC, and
      the effect of ethanol concentration, [EtOH], on the main phase transition
      temperature, T(m), and the phase structure of the lipid bilayer composed of
      C(X):C(Y)PC using differential scanning calorimetry and X-ray diffraction
      techniques [Huang and McIntosh, Biophys. J. 72 (1997) 2702--2709]. In the present
      work, we have extended these studies to characterize the effect of [EtOH] on the
      T(m) and the phase structure of the lipid bilayer composed of sn-1 saturated/sn-2
      monounsaturated phosphatidylcholines with various positions of the cis double
      bond. Specifically, five positional isomers of 1-eicosanoyl-2-eicosenoyl-sn
      glycero-3-phosphocholines, C(20):C(20:1 Delta(n))PC with n=5, 8, 11, 13 and 17,
      were synthesized and studied. For C(20):C(20:1 Delta(n))PC with n=5 and 8,
      results from the calorimetric experiments showed that in response to various
      concentrations of ethanol, the change in T(m) of the lipid bilayer composed of
      monounsaturated lipids was characterized by a sigmoidal or biphasic profile in
      the plot of T(m) versus [EtOH]. In contrast, a continuous depression of the T(m)
      by ethanol was observed calorimetrically for C(20):C(20:1 Delta(n))PC with n> or
      =11. The X-ray diffraction experiments further demonstrated that C(20):C(20:1
      Delta(5))PC and C(20):C(20:1 Delta(8))PC can undergo the ethanol-induced gel-to
      fully interdigitated phase transition at T<T(m). Such a transition, however, was
      not observed for C(20):C(20:1 Delta(13))PC even at a very high ethanol
      concentration of 100 mg/ml. These distinct different effects of [EtOH] on the
      phase transition temperature and the phase structure can be attributed to various
      positions of the cis double bond in these monounsaturated phosphatidylcholines.
      And the different effects of ethanol can, in fact, be explained based on the
      molecular structures of these monounsaturated lipids packed in the gel-state
      bilayer as generated by molecular mechanics simulations. To the best of our
      knowledge, this is the first time that the ethanol-induced fully interdigitated
      bilayers are observed at T<T(m) for unsaturated phospholipids with well defined
      double bond positions in their sn-2 acyl chains.

PMID- 11342161
TI  - Physiological evidence for an interaction between helices II and XI in the
      melibiose carrier of Escherichia coli.
AB  - The melibiose carrier from Escherichia coli is a cation-substrate cotransporter
      that catalyzes the accumulation of galactosides at the expense of H(+), Na(+), or
      Li(+) electrochemical gradients. Charged residues on transmembrane domains in the
      amino-terminal portion of this carrier play an important role in the recognition
      of cations, while the carboxyl portion of the protein seems to be important for
      sugar recognition. In the present study, we substituted Lys-377 on helix XI with
      Val. This mutant carrier, K377V, had reduced melibiose transport activity. We
      subsequently used this mutant for the isolation of functional second-site
      revertants. Revertant strains showed the additional substitutions of Val or Asn
      for Asp-59 (helix II), or Leu for Phe-20 (helix I). Isolation of revertant
      strains where both Lys-377 and Asp-59 are substituted with neutral residues
      suggested the possibility that a salt bridge exists between helix II and helix
      XI. To further test this idea, we constructed three additional site-directed
      mutants: Asp-59-->Lys (D59K), Lys-377-->Asp (K377D), and a double mutant, Asp-59-
      >Lys/Lys-377-->Asp (D59K/K377D), in which the position of these charges was
      exchanged. K377D accumulated melibiose only marginally while D59K could not
      accumulate. However, the D59K/K377D double mutant accumulated melibiose to a
      modest level although this activity was no longer stimulated by Na(+). We suggest
      that Asp-59 and Lys-377 interact via a salt bridge that brings helix II and helix
      XI close to one another in the three-dimensional structure of the carrier.

PMID- 11342162
TI  - Effects of inhibitors of the vacuolar proton pump on hepatic heterophagy and
      autophagy.
AB  - Bafilomycin A(1) (BAF) and concanamycin A (ConcA) are selective inhibitors of the
      H(+)-ATPases of the vacuolar system. We have examined the effects of these
      inhibitors on different steps in endocytic pathways in rat hepatocytes, using
      [(125)I]tyramine-cellobiose-labeled asialoorosomucoid ([(125)I]TC-AOM) and
      [(125)I]tyramine-cellobiose-labeled bovine serum albumin ([(125)I]TC-BSA) as
      probes for respectively receptor-mediated endocytosis and pinocytosis (here
      defined as fluid phase endocytosis). The effects of BAF and ConcA were in
      principle identical, although ConcA was more effective than BAF. The main
      findings were as follows. (1) BAF/ConcA reduced the rate of uptake of both
      [(125)I]TC-AOM and [(125)I]TC-BSA. The reduced uptake of [(125)I]TC-AOM was
      partly due to a redistribution of the asialoglycoprotein receptors (ASGPR) such
      that the number of surface receptors was reduced approximately 40% without a
      change in the total number of receptors. (2) BAF/ConcA at the same time increased
      retroendocytosis (recycling) of both probes. The increased recycling of the
      ligand ([(125)I]TC-AOM) is partly a consequence of the enhanced pH in endosomes,
      which prevents dissociation of ligand. (3) It was furthermore found that the
      ligand remained bound to the receptor in presence of BAF/ConcA and that the total
      amount of ligand molecules internalized in BAF/ConcA-treated cells was only
      slightly in excess of the total number of receptors. These data indicate that
      reduced pH in endosomes is the prime cause of receptor inactivation and release
      of ligand in early endosomes. (4) Subcellular fractionation experiments showed
      that [(125)I]TC-AOM remained in early endosomes, well separated from lysosomes in
      sucrose gradients. The fluid phase marker, [(125)I]TC-BSA, on the other hand,
      seemed to reach a later endosome in the BAF/ConcA-treated cells. This organelle
      coincided with lysosomes in the gradient, but hypotonic medium was found to
      selectively release a lysosomal enzyme (beta-acetylglucosaminidase), indicating
      that even [(125)I]TC-BSA remained in a prelysosomal compartment in the BAF/ConcA
      treated cells. (5) Electron microscopy using horseradish peroxidase (HRP) as a
      fluid phase marker verified that BAF/ConcA inhibited transfer of material from
      late endosomes ('multivesicular bodies'). (6) BAF/ConcA led to accumulation of
      lactate dehydrogenase (LDH) in autophagic vacuoles, but although the drugs partly
      inhibited fusion between autophagosomes and lysosomes a number of autolysosomes
      was formed in the presence of BAF/ConcA. This observation explains the reduced
      buoyant density of lysosomes (revealed in sucrose density gradients). In
      conclusion, BAF/ConcA inhibit transfer of endocytosed material from late
      endosomes to lysosomes, but do not at the same time prevent fusion between
      autophagosomes and lysosomes.

PMID- 11342163
TI  - Effect of phloretin on ionophore mediated electroneutral transmembrane
      translocations of H(+), K(+) and Na(+) in phospholipid vesicles.
AB  - Rates of M(+)/H(+) exchange (M(+)=K(+), Na(+)) across phospholipid membranes by
      ionophore mediated electroneutral translocations and transports through channels
      could either increase or decrease or change negligibly on adding the polar
      molecule phloretin to the membrane. The changes depend on pH, the concentration
      and choice of M(+) and choice of ionophore/channel. Such diverse behaviours have
      been inferred from studies on the decay of the pH difference across soybean
      phospholipid vesicular membrane (=Delta pH). The transporters used in this study
      are (a) the exchange ionophores: nigericin, monensin; (b) combinations of alkali
      metal ion carriers, valinomycin or nonactin with weak acids carbonyl cyanide m
      chlorophenylhydrazone or 2,4-dinitrophenol and (c) channels formed by gramicidin
      A. All the diverse results can be rationally explained if we take note of the
      following. (i) The rate limiting steps are associated with the transmembrane
      translocations involving the rate limiting species identified in the literature.
      (ii) Phloretin in the membrane decreases the apparent M(+) dissociation constant,
      K(M), of the M(+) bound ionophores/channels which has the effect of increasing
      the concentration of these species. (iii) The concentrations of H(+) bound
      ionophores/channels decrease on adding phloretin. (iv) Phloretin inhibits ternary
      complex formation (involving valinomycin or nonactin, M(+) and an anion) by
      forming 1:2 complexes with valinomycin-M(+) or nonactin-M(+). (v) On adding 6
      ketocholestanol to the membrane (instead of phloretin) K(M) increases. The
      decreases/increases in K(M) mentioned above are consistent with the consequences
      of a hypothesis in which phloretin decreases and 6-ketocholestanol increases the
      positive internal membrane dipole potential.

PMID- 11342164
TI  - Destabilization of neutrophil NADPH oxidase by ATP and other trinucleotides and
      its prevention by Mg(2+).
AB  - Neutrophil NADPH oxidase (O(2)(-) generating enzyme) activated in a cell-free
      system was deactivated by dilution. When ATP was included in dilution the
      deactivation was further accelerated. The deactivation by dilution was biphasic,
      and the half-life of the enzyme was significantly shortened by ATP in each phase.
      ADP and AMP had little effect on the enzyme longevity while GTP and CTP had a
      similar effect to ATP. Staurosporine, a wide-range inhibitor of protein kinases,
      had no effect on ATP-induced deactivation, suggesting that the effect was not due
      to a protein phosphorylation. Mg(2+) addition largely prevented the deactivation
      by ATP. Chemical crosslinking of the activated oxidase prevented the deactivation
      by dilution and ATP, suggesting that the deactivation is caused by dissociation
      of the oxidase complex. Estimation of actin filament (F-actin) showed that the F
      actin level was markedly reduced by addition of ATP. The ATP effect on the
      deactivation was not prominent in a semi-recombinant system which does not
      contain cytosol. These results suggest that ATP-induced deactivation is largely
      due to the chelation of Mg(2+) and are consistent with the concept that Mg(2+)
      stabilizes the oxidase complex by stabilizing F-actin.

PMID- 11342165
TI  - Characterization of sterically stabilized cisplatin liposomes by nuclear magnetic
      resonance.
AB  - Extensive scientific efforts are directed towards finding new and improved
      platinum anticancer agents. A promising approach is the encapsulation of
      cisplatin in sterically stabilized, long circulating, PEGylated 100 nm liposomes.
      This liposomal cisplatin (STEALTH cisplatin, formerly known as SPI-77) shows
      excellent stability in plasma and has a longer circulation time, greater efficacy
      and lower toxicity than much free cisplatin. However, so far, the physicochemical
      characterization of STEALTH cisplatin has been limited to size distribution, drug
      to-lipid ratio and stability. Information on the physical state of the drug in
      the liposome aqueous phases and the drug's interaction with the liposome membrane
      has been lacking. This study was aimed at filling this gap. We report a
      multinuclear NMR study in which several techniques have been used to assess the
      physical nature of cisplatin in liposomal formulations and if and to what extent
      the drug affects the liposome phospholipids. Since NMR detects only the soluble
      cisplatin in the liposomes and not the insoluble drug, combining NMR and atomic
      absorption data enables one to determine how much of the encapsulated drug is
      soluble in the intraliposomal aqueous phase. Our results indicate that almost all
      of the cisplatin remains intact during the loading process, and that the entire
      liposomal drug is present in a soluble form in the internal aqueous phase of the
      liposomes.

PMID- 11342166
TI  - Streptolysin O: the C-terminal, tryptophan-rich domain carries functional sites
      for both membrane binding and self-interaction but not for stable
      oligomerization.
AB  - Streptolysin O belongs to the class of thiol-activated toxins, which are single
      chain, four-domain proteins that bind to membranes containing cholesterol and
      then assemble to form large oligomeric pores. Membrane binding involves a
      conserved tryptophan-rich sequence motif located within the C-terminally located
      domain 4. In contrast, sites involved in oligomerization and pore formation have
      been assigned to domains 1 and 3, respectively. We here examined the functional
      properties of domain 4, which was recombinantly expressed with an N-terminal
      histidine tag for purification and an additional cysteine residue for covalent
      labeling. The fluorescently labeled fragment readily bound to membranes, but it
      did not form oligomers nor lyse cell membranes. Moreover, the labeled fragment
      did not detectably become incorporated into hybrid oligomers when combined with
      lytically active full-length toxin. However, when present in large excess over
      the active toxin, the domain 4 fragment effected reduction of hemolytic activity
      and of functional pore size, which indicates interference with oligomerization of
      the lytically active species. Our findings support the notion that domain 4 of
      the streptolysin O molecule may fold autonomously, is essential for membrane
      binding and is capable not of irreversible but of reversible association with the
      entire toxin molecule.

PMID- 11342167
TI  - Changes of structural and dynamic properties of model lipid membranes induced by
      alpha-tocopherol: implication to the membrane stabilization under external
      electric field.
AB  - The effects of alpha-tocopherol on electric properties of bilayer lipid membranes
      were investigated. Planar bilayer membranes formed by the Mueller-Rudin method
      were used. Voltammetric and chronopotentiometric measurements were performed
      using a four-electrode potentiostat-galvanostat. It was demonstrated that
      registration of membrane capacitance, resistance, and voltammetric
      characteristics provided information about the change in the structure and
      permeability of bilayer lipid membranes. The results suggested that incorporation
      of alpha-tocopherol into lipid membrane destabilized its structure and
      facilitated the electrogeneration of pores. The possible role of observed changes
      in physiological functions of alpha-tocopherol was discussed.

PMID- 11342168
TI  - Fructans insert between the headgroups of phospholipids.
AB  - Fructans are polysaccharides consisting of one glucose unit and two or more
      fructose units. It was hypothesized that fructans play a role in drought
      tolerance in plants by interacting directly with the membrane. In this paper we
      investigated this hypothesis by studying fructan-membrane interactions in
      hydrated mono- and bilayer systems. It was found that fructans inserted between
      the headgroups of different kinds of phospholipids with some preference for
      phosphatidylethanolamine. Insertion occurred even under conditions of very tight
      lipid packing. The presence of a surface associated layer of fructan was observed
      in both model systems. This layer was able to reduce the ability of a surface
      active protein to interact with the lipids. Fructans showed a much stronger
      effect on the different lipid systems than other (poly)saccharides, which appears
      to be related to their hydrophobic properties. Fructans were able to stabilize
      the liquid-crystalline lamellar phase, which is consistent with a drought
      protecting role in plants.

PMID- 11342169
TI  - Characterization of an insulin receptor-related receptor in Biomphalaria glabrata
      embryonic cells.
AB  - Tyrosine kinase receptors play a key role in the communication of cells with
      their environment. Growth hormone receptors, such as insulin receptors, are
      involved in the regulation of cell growth, differentiation and metabolism in
      multicellular organisms. Insulin-related peptides and members of the insulin
      receptor subfamily have been described in a wide variety of invertebrates,
      including freshwater molluscs. In this paper, we describe the metabolic effect of
      insulin on a mollusc cell line (Bge) derived from embryos of the snail
      Biomphalaria glabrata. Using a PCR strategy, we have cloned from Bge cells a cDNA
      encoding a protein (BgIR) homologous to, and exhibiting all of the typical
      features of insulin receptors. Northern blot analysis confirmed the expression of
      BgIR in B. glabrata snails and suggested its wide distribution in the snail body.
      Bge cells have been shown to provide the environmental conditions necessary for
      the in vitro development of the sporocysts of Schistosoma mansoni, a trematode
      parasite that uses B. glabrata as an intermediate host. The possible implication
      of BgIR in the activating and proliferating processes observed in Bge cells
      during their coculture with S. mansoni larvae is discussed.

PMID- 11342170
TI  - Organotin compounds alter the physical organization of phosphatidylcholine
      membranes.
AB  - Organotin compounds have a broad range of biological activities and are
      ubiquitous contaminants in the environment. Their toxicity mainly lies in their
      action on the membrane. In this contribution we study the interaction of
      tributyltin and triphenyltin with model membranes composed of
      phosphatidylcholines of different acyl chain lengths using differential scanning
      calorimetry, (31)P-nuclear magnetic resonance, X-ray diffraction and infrared
      spectroscopy. Organotin compounds broaden the main gel to liquid-crystalline
      phase transition, shift the transition temperature to lower values and induce the
      appearance of a new peak below the main transition peak. These effects are more
      pronounced in the case of tributyltin and are quantitatively larger as the
      phosphatidylcholine acyl chain length decreases. Both tributyltin and
      triphenyltin increase the enthalpy change of the transition in all the
      phosphatidylcholine systems studied except in dilauroylphosphatidylcholine.
      Organotin compounds do not affect the macroscopic bilayer organization of the
      phospholipid but do affect the degree of hydration of its carbonyl moiety. The
      above evidence supports the idea that organotin compounds are located in the
      upper part of the phospholipid palisade near the lipid/water interface.

PMID- 11342171
TI  - Oxidative and drug-induced alterations in brush border membrane hemileaflet
      fluidity, functional consequences for glucose transport.
AB  - Oxidation of biological membranes has been suggested as a major pathological
      process in a variety of disease states including intestinal ischemia and
      inflammatory bowel disease. Previous studies on the small intestinal brush border
      membrane have shown that part of the decrease in the activity of the Na(+)
      dependent glucose transporter (SGLT1) observed after oxidation could be secondary
      to the derangement in membrane fluidity that accompanied oxidative damage. The
      present study examined the relationship between oxidative-induced hemileaflet
      fluidity alterations and the resultant change in Na(+)-dependent glucose
      transport activity. To address this issue, in vitro oxidation of guinea pig brush
      border membrane vesicles was induced by incubation of the vesicles with ferrous
      sulfate and ascorbate. We found that oxidation decreased the fluidity of both the
      outer and inner hemileaflets, the decrease being greater in the outer leaflet.
      Moreover, the preferential alteration in hemileaflet fluidity was accompanied by
      a decrease in glucose transport. However, when membrane perturbing agents such as
      hexanol and A(2)C were used to restore membrane fluidity to levels comparable to
      controls, rates of glucose transport could not be interpreted in terms of
      variation of bulk membrane fluidity or variation in fluidity of any specific
      membrane leaflet. On the basis of these experiments, we propose that previous
      studies that reported coincidental alteration in membrane fluidity and glucose
      transport cannot be interpreted on the basis of bulk fluidity or hemileaflet
      fluidity.

PMID- 11342172
TI  - Glycans are involved in RANTES binding to CCR5 positive as well as to CCR5
      negative cells.
AB  - We show that cell surface glycans, sialic acid and mannose-containing species,
      are involved beside glycosaminoglycans (GAGs), heparan sulfate and chondroitin
      sulfate in the binding of full length (1--68) RANTES not only to CCR5 positive
      human primary lymphocytes or macrophages but also to CCR5 negative monocytic U937
      cells. Pretreating the cells with neuraminidase, heparitinase, chondroitinase or
      adding soluble glycans such as mannan or GAGs (heparin or chondroitin sulfate),
      significantly inhibited RANTES binding. Such effects were not observed with
      truncated (10--68) RANTES. Heat-denaturation of (1--68) RANTES strongly decreased
      its binding to the cells, demonstrating involvement of the three-dimensional
      structure. Accordingly, full length, but not truncated (10--68) RANTES,
      specifically bound to soluble mannan as well as to mannose-divinylsulfone-agarose
      affinity matrix and to soluble heparin or chondroitin sulfate as well as to
      heparin-agarose. Soluble heparin exerts, depending on its concentration,
      inhibitory or enhancing effects on RANTES binding to mannose-divinylsulfone
      agarose, which indicates that RANTES interaction with glycans is modulated by
      GAGs. These data demonstrate that full length RANTES, but not its (10--68)
      truncated counterpart, interacts with glycans and GAGs, in soluble forms or
      presented either by affinity matrices or CCR5 positive as well as CCR5 negative
      cells.

PMID- 11342173
TI  - Effects of efrapeptin and destruxin, metabolites of entomogenous fungi, on the
      hydrolytic activity of a vacuolar type ATPase identified on the brush border
      membrane vesicles of Galleria mellonella midgut and on plant membrane bound
      hydrolytic enzymes.
AB  - The brush border membrane of the insect midgut is an initial site for interaction
      of insecticidal proteins. We have investigated the possibility that it may
      contain a target site for two insecticidal fungal toxins, destruxin and
      efrapeptin, both of which are ATPase inhibitors. We have studied the effects of
      the toxins on the hydrolytic activity of a vacuolar type ATPase (V-ATPase) that
      we have identified from Galleria mellonella midgut columnar cell brush border
      membrane vesicles (BBMV) by its cation and pH dependence, sensitivity to proton
      pump inhibitors and K(m) (0.49 mM ATP). Efrapeptin strongly inhibited the BBMV V
      ATPase but destruxin had little effect. We compared the effects of the inhibitors
      on known plant membrane hydrolytic enzymes, and although the vacuolar
      pyrophosphatase and plasma membrane ATPase were not inhibited by the toxins, the
      V-ATPase from mung bean, but not barley, was inhibited (50%) by 10 microM
      concentrations of both compounds. Different forms of the toxins were tested on
      the ATPases and destruxin B and efrapeptin F were the most effective. Kinetic
      analysis showed that the purified forms of both compounds inhibited the V-ATPases
      uncompetitively and modelling of data for inhibition of the BBMV V-ATPase by
      efrapeptin at concentrations of 0.06--12 microM yielded a K(i) of 0.125 microM.

PMID- 11342174
TI  - Covalent modification of the non-catalytic sites of the H(+)-ATPase from
      chloroplasts with 2-azido-[alpha-(32)P]ATP and its effect on ATP synthesis and
      ATP hydrolysis.
AB  - Incubation of the isolated H(+)-ATPase from chloroplasts, CF(0)F(1), with 2-azido
      [alpha-(32)P]ATP leads to the binding of this nucleotide to different sites.
      These sites were identified after removal of free nucleotides, UV-irradiation and
      trypsin treatment by separation of the tryptic peptides by ion exchange
      chromatography. The nitreno-AMP, nitreno-ADP and nitreno-ATP peptides were
      further separated on a reversed phase column, the main fractions were subjected
      to amino acid sequence analysis and the derivatized tyrosines were used to
      distinguish between catalytic (beta-Tyr362) and non-catalytic (beta-Tyr385)
      sites. Several incubation procedures were developed which allow a selective
      occupation of each of the three non-catalytic sites. The non-catalytic site with
      the highest dissociation constant (site 6) becomes half maximally filled at 50
      microM 2-azido-[alpha-(32)P]ATP, that with the intermediate dissociation constant
      (site 5) at 2 microM. The ATP at the site with the lowest dissociation constant
      had to be hydrolyzed first to ADP before a replacement by 2-azido-[alpha
      (32)P]ATP was possible. CF(0)F(1) with non-covalently bound 2-azido-[alpha
      (32)P]ATP and after covalent derivatization was reconstituted into liposomes and
      the rates of ATP synthesis as well as ATP hydrolysis were measured after
      energization of the proteoliposomes by Delta pH/Delta phi. Non-covalent binding
      of 2-azido-ATP to any of the three non-catalytic sites does not influence ATP
      synthesis and ATP hydrolysis, whereas covalent derivatization of any of the three
      sites inhibits both, the degree being proportional to the degree of
      derivatization. Extrapolation to complete inhibition indicates that
      derivatization of one site (either 4 or 5 or 6) is sufficient to block completely
      multi-site catalysis. The rates of ATP synthesis and ATP hydrolysis were measured
      as a function of the ADP and ATP concentration from uni-site to multi-site
      conditions with covalently derivatized and non-derivatized CF(0)F(1). Uni-site
      ATP synthesis and ATP hydrolysis were not inhibited by covalent derivatization of
      any of the non-catalytic sites, whereas multi-site catalysis is inhibited. These
      results indicate that multi-site catalysis requires some flexibility between beta
      and alpha-subunits which is abolished by covalent derivatization of beta-Tyr385
      with a 2-nitreno-adenine nucleotide. Conformational changes connected with energy
      transduction between the F(0)-part and the F(1)-part are either not required for
      uni-site ATP synthesis or they are not impaired by the derivatization of any of
      the three beta-Tyr385.

PMID- 11342175
TI  - The specificity of monoglyceride-protein interactions and mechanism of the
      protein induced L(beta) to coagel phase transition.
AB  - This study aims at gaining insight into the specificity and molecular mechanism
      of monoglyceride-protein interactions. We used beta-lactoglobulin (beta-LG) and
      lysozyme as model proteins and both monostearoylglycerol and
      monopalmitoylglycerol as defined gel phase monoglycerides. The monoglycerides
      were used in different combinations with the two negatively charged amphiphiles
      dicetylphosphate and distearylphosphate. The interactions were characterized
      using the monolayer technique, isothermal titration calorimetry, (2)H-nuclear
      magnetic resonance (NMR) using deuterium labelled monoglycerides and freeze
      fracture electron microscopy (EM). Our results show that lysozyme inserts
      efficiently into all monolayers tested, including pure monoglyceride layers. The
      insertion of beta-LG depends on the lipid composition of the monolayer and is
      promoted when the acylchains of the negatively charged amphiphile are shorter
      than that of the monoglyceride. The binding parameters found for the interaction
      of beta-LG and lysozyme with monoglyceride bilayers were generally similar.
      Moreover, in all cases a large exothermic binding enthalpy was observed which was
      found to depend on the nature of the monoglycerides but not of the proteins. (2)H
      NMR and freeze fracture EM showed that this large enthalpy results from a protein
      mediated catalysis of the monoglyceride L(beta) to coagel phase transition. The
      mechanism of this phase transition consists of two steps, an initial protein
      mediated vesicle aggregation step which is followed by stacking and probably
      fusion of the bilayers.

PMID- 11342176
TI  - Trifluoperazine induces domain formation in zwitterionic phosphatidylcholine but
      not in charged phosphatidylglycerol bilayers.
AB  - The interaction of trifluoperazine with the zwitterionic lipids
      dipalmitoylphosphatidylcholine and dimyristoylphosphatidylcholine and with
      anionic dimyristoylphosphatidylglycerol was studied by means of microcalorimetry
      and fluorescence spectroscopy. Intercalation of drug molecules into the lipid
      bilayers was confirmed by the observed differential scanning calorimetry peak
      broadening and the decrease in chain-melting temperatures. For
      trifluoperazine:lipid mole ratios higher than 0.4 and 0.6 (for
      dipalmitoylphosphatidylcholine and dimyristoylphosphatidylcholine, respectively)
      the deconvolution of transition profiles into two Gaussian components was
      possible, which suggests phase separation in the studied mixtures. Deconvolution
      of the thermograms was not possible for any of the
      drug:dimyristoylphosphatidylglycerol mole ratios studied. To confirm the
      existence of phase separation in trifluoperazine-phosphatidylcholine mixtures
      fluorescence spectroscopy experiments were performed using Laurdan as a probe.
      From the generalised polarisation versus excitation wavelength dependences,
      recorded at different temperatures, we conclude that a phase separation occurs in
      the gel state of the studied trifluoperazine-phosphatidylcholine mixtures. We
      attribute the existence of domains in the bilayer to the dissimilar interactions
      of two protonation forms of trifluoperazine with phosphatidylcholine molecules.
      Structural defects present at domain boundaries could be related to the
      trifluoperazine induced increase of membrane permeability and fluidity. This may
      partially explain the mechanism of multidrug resistance modulation by
      trifluoperazine.

PMID- 11342177
TI  - Vesicular monoamine transporters heterologously expressed in the yeast
      Saccharomyces cerevisiae display high-affinity tetrabenazine binding.
AB  - A mammalian vesicular neurotransmitter transporter has been expressed in the
      yeast Saccharomyces cerevisiae. The gene encoding the rat vesicular monoamine
      transporter (rVMAT(1)) was cloned in several expression plasmids. The transporter
      was expressed at detectable levels only when short sequences using codons favored
      by S. cerevisiae were fused preceding the start of translation of rVMAT(1). The
      scarce expression of the wild-type protein was, most likely, due to the fact that
      part of the N-terminus of the protein is encoded by codons not preferred in S.
      cerevisiae. Furthermore, low growth temperatures increased rVMAT(1) expression
      and altered its processing. Whereas at 30 degrees C the protein is not
      glycosylated, at lower temperatures ( approximately 16 degrees C) half of the
      expressed transporters undergo core glycosylation. In addition, under these
      conditions the levels of protein expression significantly increase. Using a
      functional chimeric protein composed by VMAT and the green fluorescent protein
      (GFP), it is shown that the punctate pattern of intracellular distribution
      remains invariable at the different temperatures. Using a similar fusion
      sequence, the bovine VMAT isoform 2 (bVMAT(2)) was also expressed in yeast. The
      yeast-expressed bVMAT(2) binds [(3)H]dihydrotetrabenazine ([(3)H]TBZOH) with the
      same characteristics found in the native protein from bovine chromaffin granules.
      Dodecyl maltoside-solubilized bVMAT(2) retains the conformation required for
      [(3)H]TBZOH binding. We exploited the robust binding to follow the transporter
      during purification assays on a Ni(2+)-chelating column. In this report we
      describe for the first time the heterologous expression of a neurotransmitter
      transporter in the yeast S. cerevisiae.

PMID- 11342178
TI  - Inhibition by mercuric chloride of Na-K-2Cl cotransport activity in rectal gland
      plasma membrane vesicles isolated from Squalus acanthias.
AB  - The rectal gland of the dogfish shark is a model system for active
      transepithelial transport of chloride. It has been shown previously that mercuric
      chloride, one of the toxic environmental pollutants, inhibits chloride secretion
      in this organ. In order to investigate the mechanism of action of HgCl(2) at a
      membrane-molecular level, plasma membrane vesicles were isolated from the rectal
      gland and the effect of mercury on the activity of the Na-K-2Cl cotransporter was
      investigated in isotope flux studies. During a 30 s exposure HgCl(2) inhibited
      cotransport activity in a dose-dependent manner with an apparent K(i) of approx.
      50 microM. The inhibition was complete after 15 s, partly reversible by dilution
      of the incubation medium and completely attenuated upon addition of reduced
      glutathione. The extent of inhibition by mercury depended on the ionic
      composition of the medium. The sensitivity of the cotransporter was highest when
      only the high affinity binding sites for sodium and chloride were saturated.
      Organic mercurials such as p-chloromercuribenzoic acid and p
      chloromercuriphenylsulfonic acid at 100 microM did not inhibit the cotransporter,
      similarly exposure of the vesicles to 10 mM H(2)O(2) or 1 mM dithiothreitol for
      30 min at 15 degrees C did not change cotransport activity. Transport activity
      was, however, reduced by 45.9+/-2.5% after an incubation with 3 mM N
      ethylmaleimide for 20 min. Blocking free amino groups by N-hydroxysuccinimide or
      biotinamidocapronate-N-hydroxysulfosuccinimide had no effect. Investigations on
      the sidedness of the plasma membrane vesicles, employing the asymmetry of the
      (Na+K)-ATPase, demonstrated a right-side-out orientation in which the former
      extracellular face of the membrane is exposed to the incubation medium. In
      addition, extracellular mercury (5x10(-5) M) inhibited bumetanide-sensitive
      rubidium uptake into T84 cells by 48.5+/-7.1% after a 2 min incubation period.
      This inhibition was reversible in a manner similar to that observed in the plasma
      membrane vesicles. These studies suggest that in isolated rectal gland plasma
      membrane vesicles the Na-K-2Cl cotransporter (sNKCC1) exposes functionally
      relevant mercury binding sites at its external surface. These sites represent
      probably cysteines, the accessibility and/or sensitivity of which depends on the
      functional state of the transporter.

PMID- 11342179
TI  - Interaction of the antimicrobial peptide gramicidin S with dimyristoyl-
      phosphatidylcholine bilayer membranes: a densitometry and sound velocimetry
      study.
AB  - We determined changes in the volume and adiabatic compressibility of large multi-
      and unilamellar vesicles composed of dimyristoylphosphatidylcholine containing
      various concentrations of the antimicrobial peptide gramicidin S (GS) by applying
      densitometry and sound velocimetry. Gramicidin S incorporation was found to
      progressively decrease the phase transition temperature of DMPC vesicles as well
      as to decrease the degree of cooperativity of the main phase transition and to
      increase the volume compressibility of the vesicles. GS probably enhanced thermal
      fluctuations at the region of main phase transition and provide more freedom of
      rotational movement for the phospholipid hydrocarbon chains. The ability of GS to
      increase the membrane compressibility and to decrease the phase transition
      temperature is evidence for regions of distorted membrane structure around
      incorporated gramicidin S molecules. At relatively high GS concentration (10
      mol%), more significant changes of specific volume and compressibility appear.
      This might suggest changes in the integrity of the lipid bilayer upon interaction
      with high concentrations of GS.

PMID- 11342180
TI  - Specific spin labelling of the sugar-H(+) symporter, GalP, in cell membranes of
      Escherichia coli: site mobility and overall rotational diffusion of the protein.
AB  - The D-galactose-H(+) symport protein (GalP) of Escherichia coli is a homologue of
      the human glucose transport protein, GLUT1. After amplified expression of the
      GalP transporter in E. coli, other membrane proteins were prereacted with N
      ethylmaleimide in the presence of excess D-galactose to protect GalP. Inner
      membranes were then specifically spin labelled on Cys(374) of GalP with 4
      maleimide-2,2,6,6-tetramethylpiperidine-1-oxyl. The electron paramagnetic
      resonance (EPR) spectra are characteristic of a single labelling site in which
      the mobility of the spin label is very highly constrained. This is confirmed with
      other nitroxyl spin labels, which are derivatives of iodoacetamide and
      indanedione. Saturation transfer EPR spectra indicate that the overall rotation
      of the GalP protein in the membrane is slow at low temperatures (approx. 2
      degrees C), but considerably more rapid and highly anisotropic at physiological
      temperatures. The rate of rotation about the membrane normal at 37 degrees C is
      consistent with predictions for a 12-transmembrane helix assembly that is less
      than closely packed.

PMID- 11342181
TI  - Biochemical characterization of integral membrane heparan sulfate proteoglycans
      in Sertoli cells from immature rat testis.
AB  - (35)S-Radiolabeled cultured Sertoli cells from immature rat testis were extracted
      with detergent and the different proteoheparan sulfate (HSPG) forms of the
      extract were discriminated and quantified on the basis of their high anionic
      charge, hydrodynamic size, lipophilic properties, susceptibility to trypsin and
      phosphatidylinositol phospholipase C (PI-PLC). Trypsin released 50% of total
      cellular HSPG corresponding to 80% of total hydrophobic HSPG. Trypsin-accessible
      HSPG were presumed to be integral membrane species. Trypsin-resistant HSPG,
      probably intracellular, distributed into non-lipophilic (37.5%) and lipophilic
      (12.5%) populations. Biochemical analysis of PG copurified with plasma membrane
      confirmed the existence of hydrophobic HSPG integrated into this structure. Among
      hydrophobic HSPG accessible to trypsin, 35% were PI-PLC released and radiolabeled
      by [(3)H]inositol indicating that about one third of integral membrane HSPG were
      intercalated into the plasma membrane through a phosphatidylinositol anchor
      (glypican type). PI-PLC-resistant forms represented HSPG inserted into the
      membrane through a hydrophobic segment of the core protein (syndecan type). No
      lipophilic PG was present in other cell compartments (culture medium, cell
      periphery, extracellular matrix). (125)I-Iodinated hydrophobic HSPG were
      deglycanated and submitted to SDS-polyacrylamide gel electrophoresis. In the
      glypican family, a core protein (64--65 kDa) was detected, whereas in the
      syndecan family, bands of 60 and 68 kDa were observed which may correspond to
      self-association of different core proteins. In Sertoli cell, specific functional
      attributes of different integral membrane HSPG forms remain to be investigated.

PMID- 11342182
TI  - Immunization-related products: introduction to the panel discussion.

PMID- 11342183
TI  - The use of common genetic polymorphisms to enhance the epidemiologic study of
      environmental carcinogens.
AB  - Overwhelming evidence indicates that environmental exposures, broadly defined,
      are responsible for most cancer. There is reason to believe, however, that
      relatively common polymorphisms in a wide spectrum of genes may modify the effect
      of these exposures. We discuss the rationale for using common polymorphisms to
      enhance our understanding of how environmental exposures cause cancer and comment
      on epidemiologic strategies to assess these effects, including study design,
      genetic and statistical analysis, and sample size requirements. Special attention
      is given to sources of potential bias in population studies of gene--environment
      interactions, including exposure and genotype misclassification and population
      stratification (i.e., confounding by ethnicity). Nevertheless, by merging
      epidemiologic and molecular approaches in the twenty-first century, there will be
      enormous opportunities for unraveling the environmental determinants of cancer.
      In particular, studies of genetically susceptible subgroups may enable the
      detection of low levels of risk due to certain common exposures that have eluded
      traditional epidemiologic methods. Further, by identifying susceptibility genes
      and their pathways of action, it may be possible to identify previously
      unsuspected carcinogens. Finally, by gaining a more comprehensive understanding
      of environmental and genetic risk factors, there should emerge new clinical and
      public health strategies aimed at preventing and controlling cancer.

PMID- 11342184
TI  - A new family of IKK-related kinases may function as I kappa B kinase kinases.

PMID- 11342185
TI  - Regulation of the p53 pathway by Ras, the plot thickens.

PMID- 11342186
TI  - Mouse models of neurofibromatosis.

PMID- 11342187
TI  - Centrosome abnormalities, genomic instability and carcinogenic progression.
AB  - Centrosome abnormalities are a frequent finding in various malignant tumors.
      Since centrosomes form the poles of the mitotic spindle, these abnormalities have
      been implicated in chromosome missegregation and the generation of aneuploid
      cells which is commonly found in many human neoplasms. It is a matter of debate,
      however, whether centrosome alterations can drive cells into aneuploidy or simply
      reflect loss of genomic integrity by other mechanisms. Since these two models
      have fundamentally different implications for the diagnostic and prognostic value
      of centrosome abnormalities, we will discuss the relevance of abnormal
      centrosomes in the context of different oncogenic events as exemplified by high
      risk human papillomavirus-associated carcinogenesis.

PMID- 11342188
TI  - The role of beta-tubulin isotypes in resistance to antimitotic drugs.

PMID- 11342190
TI  - Erratum to: Is attentional focusing an inhibitory process at distractor
      location?.

PMID- 11342189
TI  - Molecular biology and experimental models for hematologic malignant diseases:
      workshop of the NIH Pathology B Study Section.

PMID- 11342193
TI  - Introduction.

PMID- 11342194
TI  - The value of the human epidermal growth factor receptor-2 (HER2) as a prognostic
      marker.
AB  - The prognosis for patients with breast cancer is determined by well-established
      pathological features associated with biological aggressiveness, histological
      grade, tumour size and nodal involvement. These remain the key determinants,
      despite the identification of numerous other potential biological markers. The
      use of prognostic indices, such as the Nottingham Prognostic Index (NPI), which
      combines and weights these factors, enables clinicians to predict outcome with a
      certain amount of accuracy. Approximately 20-30% of breast cancers express very
      high quantities of the human epidermal growth factor receptor-2 (HER2) protein
      and this is almost always associated with gene amplification. With the use of
      sensitive techniques, such as the radio-immunohistochemical method (rIHC)
      described herein, to quantify HER2 protein levels, up to a further 50% of such
      cancers will be found to express the HER2 receptor at least 4-fold higher than
      normal breast cells. Adding HER2 expression to the NPI helps to determine more
      accurately the prognosis for individual patients, particularly those with node
      negative disease. Overall, the main value of HER2 measurement is likely to be in
      the prediction of response to therapies targeting the HER2 gene and protein.

PMID- 11342195
TI  - Assessment of the need and appropriate method for testing for the human epidermal
      growth factor receptor-2 (HER2).
AB  - The human epidermal growth factor receptor-2 (HER2) gene (also known as c-erbB-2
      or neu) is amplified in 20-30% of breast cancers. HER2 gene amplification and
      HER2 overexpression occur early in the development of breast cancers and are
      found in a high proportion of ductal carcinomas in situ (DCIS), non-invasive
      cancers that generally do not give rise to metastases. In DCIS, HER2
      overexpression is found specifically in poorly histologically differentiated
      disease and not in well differentiated cancers. Various methods have been used to
      analyse the HER2 status of a tumour. These either measure the degree of HER2 gene
      amplification, receptor overexpression or the amount of circulating HER2 protein.
      In practice, immunohistochemistry is the most frequently used method, being
      available as a standard technique in all pathology laboratories. It is of
      critical importance to standardise the methods used for staining and to apply
      common interpretation criteria to enable direct comparison of results between
      laboratories.

PMID- 11342196
TI  - Clinical trials of Herceptin(R) (trastuzumab).
AB  - This report summarises the clinical efficacy and safety findings from clinical
      trials of the new anti-HER2 monoclonal antibody Herceptin(R) (trastuzumab). Data
      from pivotal trials indicate that trastuzumab is active when added to
      chemotherapy in patients with advanced metastatic breast cancer. In particular,
      the combination significantly prolonged the median time to disease progression,
      increased the overall response rate, increased the duration of response, and
      improved median survival time by approximately 25% compared with chemotherapy
      alone. Furthermore, trastuzumab is active as a single agent in women with HER2
      positive metastatic breast cancer, inducing durable objective tumour responses.
      In total, 15% of patients who had received extensive prior treatment for
      metastatic disease had an objective response. The median duration of response was
      9.1 months following administration of single-agent trastuzumab. Notably, 2% of
      patients were free of disease progression at 6 months. The safety profile of
      trastuzumab either given alone or in combination was favourable.

PMID- 11342197
TI  - First-line, single-agent Herceptin(R) (trastuzumab) in metastatic breast cancer.
      a preliminary report.
AB  - Following confirmation of the appropriate dosage, safety and potential efficacy
      of Herceptin(R) (trastuzumab) in small-scale phase I and II trials involving
      patients with refractory disease, a large trial was conducted in 222 patients
      with breast cancer who had relapsed after one or two chemotherapy regimens for
      their metastatic disease. The results showed a positive and durable overall
      response rate (15% according to a response evaluation committee (REC) assessment)
      using trastuzumab monotherapy (initial dose 4 mg/kg intravenously (i.v.) followed
      by 2 mg/kg i.v. weekly). In another recently completed phase II trial, 113
      patients were randomised to two dose levels (initial dose of 4 mg/kg i.v. dose
      followed by 2 mg/kg i.v. weekly, or initial dose of 8 mg/kg followed by 4 mg/kg
      i.v. weekly) of single-agent trastuzumab as first-line therapy for metastatic
      disease. The preliminary overall response rate was 23% based on investigator
      assessment, and tolerability was excellent as in previous trials; efficacy was
      similar in both dose groups, but the side-effects tended to be more frequent in
      the higher dose group. The preferred dosage is therefore the same as that
      currently recommended, i.e. an initial dose of 4 mg/kg i.v. followed by 2 mg/kg
      weekly i.v. until disease progression.

PMID- 11342198
TI  - Closing remarks and treatment guidelines.
AB  - The human epidermal growth factor receptor HER2 or C-erbB-2/neu is a tyrosine
      kinase membrane receptor, which when activated, induces a phosphorylation cascade
      in cytoplasmic kinases leading to increased protein transcription and cellular
      growth. HER2 plays an important role in the biology of breast cancer, an
      observation that has led to the selection of HER2 as a potential target for
      breast cancer treatment. Trastuzumab (Herceptin(R)) is the first anti-HER2
      monoclonal antibody that has shown a survival benefit in metastatic breast cancer
      patients with HER2-positive tumours (Norton et al., Proc ASCO 2000 18, 127a
      (abstract 483)). Tumour HER2 status should no longer be ignored because of its
      direct implications for the optimal management of breast cancer patients. A high
      priority for future research is to refine and standardise HER2 testing in order
      to minimise false-negative results. Furthermore, this procedure would overcome
      current issues relating to test reproducibility between pathology laboratories
      and definitions of HER2 positivity. In the meantime, a HER2-positive status on
      testing using any approved technique has implications for clinical practice (Fig.
      1). The treatment algorithm given in Fig. 1 considers the lack of level 1,
      evidence-based studies that demonstrate convincingly the value of HER2 as a
      predictive marker for resistance or sensitivity to classic forms of breast cancer
      therapy (Piccart et al., Eur J Cancer 2000, 36, 1755-1761). In addition, the
      algorithm incorporates the available data from 1999-2000, which were generated
      from prospective trials exploring the value of trastuzumab both as a single agent
      and in combination with chemotherapy.

PMID- 11342201
TI  - An association between plasma free protein s concentration and risk of coronary
      heart disease in middle-aged men.
AB  - Protein S is a vitamin K-dependent protein with anticoagulant properties. Case
      series have reported reduced plasma concentrations in patients with arterial
      thromboses, while other studies have reported increased levels in patients with
      coronary heart disease (CHD). The present study sought to clarify the relation
      between free protein S and risk of CHD. A prospective survey was conducted of
      3000 men aged 50 to 61 years, free of clinical CHD at baseline. Free protein S
      was measured by commercial immunoassay. End-points recorded were sudden coronary
      death, first nonfatal and fatal myocardial infarction (MI), surgical intervention
      for symptomatic, angiographically demonstrated CHD, and all-causes mortality.
      Statistical analysis employed univariate incidence rate ratios followed by Cox
      proportional hazards regression. There were 168 CHD events recorded during 21,000
      person-years of risk. Mean free protein S concentration was 6% higher in those
      who developed CHD than in the remainder, the crude hazard ratio (HR) for a one
      standard deviation (S.D.) increase in free protein S being 1.25 (95% CI, 1.08
      1.25). Free protein S was associated with cholesterol concentration and other
      conventional CHD risk factors. In multivariate regression analysis, after
      adjustment for conventional CHD risk factors a 1 S.D. increase in free protein S
      was associated with a HR of 1.15 (0.98-1.35) for CHD, of borderline conventional
      statistical significance. This association of free protein S with risk of CHD may
      reflect effects of plaque-destabilising inflammatory activity on protein S
      levels.

PMID- 11342202
TI  - Hemostatic activation in acute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to examine the association
      between hemostatic activation and stroke severity, and to provide data on
      hemostatic variables in acute ischemic stroke. METHODS: The patient material
      comprised 76 consecutive patients with acute ischemic stroke (median 16 h,
      interquartile range 3-48). Levels of hemostatic variables were determined in
      blood samples collected on the day of hospitalization. Stroke severity was
      assessed on admission by the Oxfordshire Community Stroke Project (OCSP)
      classification, and on discharge (median 9 days, interquartile range 6-14) by
      Barthel Index (BI, scores 0-50, 55-90, or 95-100) and modified Rankin Scale (mRS,
      scores 0-1 or 2-6). Associations were assessed by multiple linear regression
      analyses. RESULTS: Levels of the fibrin degradation product D-Dimer and the
      activation peptide prothrombin fragment 1 + 2 (F1 + 2) were linearly related to
      stroke severity, whether assessed on admission (P = .001 and.03, respectively,
      for the OCSP classification), or on discharge (P = .009 and.43, respectively, for
      BI; and.001 and.05, respectively, for mRS). High levels of D-Dimer and F(1 + 2),
      as well as low levels of antithrombin and protein C were also present in patients
      with a presumed embolic source, and low antithrombin or protein C was borderline
      significantly associated with atrial fibrillation (P = .072 and.058,
      respectively). Low levels of protein C or protein S, and the presence of
      antiphospholipid antibodies, including lupus anticoagulant (LA), was detected in
      13/73 (18%) and 15/70 (21%) of the patients, respectively. CONCLUSION: Activation
      of the hemostatic system is independently related to acute stroke severity and
      short-term outcome. Low levels of coagulation inhibitors or presence of
      antiphospholipid antibodies is a relatively frequent finding in unselected
      patients with acute ischemic stroke, but a causative role cannot be inferred from
      our study.

PMID- 11342203
TI  - Post-thrombotic syndrome after primary event of deep venous thrombosis 10 to 20
      years ago.
AB  - AIMS: We investigated the impact of the extent of primary deep venous thrombosis
      (DVT) and recurrent thrombotic events in accordance to other presumed prognostic
      factors for long-term clinical outcome after first DVT. PATIENTS AND METHODS: All
      consecutive in-patients, who were treated following first acute DVT between
      January 1, 1978 and December 31, 1988 at the Department of Angiology were
      identified by admission lists. Localisation, extent of primary DVT, etiology and
      concomitant pulmonary embolism (PE) at the time of initial presentation and
      occurrence of post-thrombotic syndrome (PTS) at follow-up visits were assessed by
      chart review. The duration and quality of the compression therapy, as well as the
      accuracy of the oral anticoagulant (OAC) treatment were documented. Recurrence of
      thrombosis embolism and/or PE with respect to the intensity of OAC was analyzed.
      Patients were invited to participate in clinical reinvestigation. Patients'
      history and clinical stage of PTS were re-evaluated and patients were asked for
      compliance in wearing compression stockings. A survey concerning restriction in
      quality of life was conducted. Hemodynamic measurements by strain-gauge
      plethysmography (SGP) were performed. RESULTS: One hundred and sixty-one patients
      were eligible for the study. Out of these 132 patients, 82% suffered from the
      PTS, defined as signs of chronic venous insufficiency (CVI) secondary to DVT of
      the lower limbs: 74 patients (46%) presented with clinical stage I after Widmer,
      47 patients (29%) with clinical stage II and 11 patients (7%) with clinical stage
      III. No sign of PTS was seen in 29 patients (18%). The mean follow-up period of
      6.6 years was statistically not different between the three severity groups of
      PTS. The severity of clinical symptoms was significantly associated with the
      recurrence of ipsilateral thrombosis (n = 26/16%). Highest risk for developing
      severe PTS was seen after four-level DVT and deep vein thrombosis of the lower
      leg. Patients having had a non-sufficient OAC (Hepatoquick > 25% in more than 50%
      of measurements) exhibited worse progradient clinical stages. Besides the high
      rate of bleeding complications after thrombolytic therapy, this strategy did not
      show more efficiency in prevention of development of severe PTS than heparin
      therapy alone. CONCLUSION: Our results show that primary four-level DVT, calf
      vein thrombosis, recurrence of ipsilateral DVT and a non-sufficient oral
      anticoagulation are of prognostic significance for developing clinically relevant
      PTS within 10 to 20 years after first DVT.

PMID- 11342204
TI  - Association of circulating cellular adhesion molecules with menopausal status and
      hormone replacement therapy. Time-dependent change in transdermal, but not oral
      estrogen users.
AB  - The incidence of coronary heart disease is lower in premenopausal than in
      postmenopausal women, and estrogen use may be cardioprotective among
      postmenopausal women. Cellular adhesion molecules (CAM) are involved in the early
      stage of atherosclerosis, and short-term administration of oral estrogen
      decreased plasma concentrations of their soluble forms in postmenopausal women.
      However, data evaluating transdermal estrogen are sparse and long-term effect of
      hormone replacement therapy (HRT) on CAM is unknown. Therefore, we have
      investigated the association of circulating CAM (cCAM) with menopausal status and
      long-term HRT. Plasma levels of intercellular adhesion molecule-1 (cICAM-1),
      vascular cell adhesion molecule-1 (cVCAM-1), P-selectin, E-selectin, C-reactive
      protein (CRP), and fibrinogen were measured in 74 premenopausal women, 60
      postmenopausal women not using HRT, 30 postmenopausal women using opposed oral
      estrogen therapy, and 30 postmenopausal women using opposed transdermal estrogen
      therapy. All women were apparently healthy and aged between 45 and 54 years.
      Duration of HRT ranged from 3 to 96 months. Postmenopausal women not receiving
      HRT had 24% higher mean levels of cICAM-1 than premenopausal women (318 vs. 255
      ng/ml, P < .001). In postmenopausal women, users of oral estrogen had 16% lower,
      and users of transdermal estrogen had 17% lower mean levels of cICAM-1 than non
      users (268 and 264 vs. 318 ng/ml, P = .001 for both comparisons). Furthermore, in
      users of transdermal route, the lowering effect of estrogen on cICAM-1 was
      dependent on treatment duration, while no time-dependent effect was seen in oral
      estrogen users. Users of transdermal estrogen had lower cVCAM-1 and P-selectin
      levels than postmenopausal non-users (327 vs. 364 ng/ml (P = .05) and 18 vs. 23
      ng/ml (P = .05). There was no difference in CRP and E-selectin levels between the
      groups. Adjustment for age and body mass index (BMI) made no substantial change
      in the results. These data suggest that oral and transdermal estrogen may play a
      long-term cardioprotective role through favourable changes in endothelial
      function.

PMID- 11342205
TI  - As compared to kaolin clotting time, silica clotting time is a specific and
      sensitive automated method for detecting lupus anticoagulant.
AB  - Lupus anticoagulants (LAs) are antiphospholipid antibodies capable of interfering
      with the coagulation system and modifying in vitro the phospholipid-dependent
      clotting tests. Colloidal silica was used as activator to perform an activated
      partial thromboplastin time (aPTT) in 73 plasma samples with pathologically
      elevated kaolin clotting time (KCT) values using a photooptical automated
      coagulometer. Samples were incubated for 5 min with micronized silica, and after
      recalcification, the clotting times were measured. Pathologically prolonged
      results were confirmed by a confirmation and a neutralization test adding
      platelet-poor normal plasma (PPNP) and natural phospholipids, respectively.
      Silica clotting time (SCT) was abnormally elevated in 72/73 (98.6%) (mean ratio
      1.71 +/- 0.28) KCT positive samples and normalized (mean ratio 1.03 +/- 0.16)
      after adding natural phospholipids to test plasma. The values expressed as SCT
      and KCT ratios were significantly correlated (r = .92; P < .001). SCT was normal
      in 40 healthy subjects utilised as controls (mean ratio 0.99 +/- 12).
      Sensitivity, specificity and diagnostic accuracy of SCT were 98.6%, 100% and
      97.6%, respectively. Our data suggest that SCT is a sensitive test for detecting
      LA with a prolonged KCT in automated photooptical coagulometers. This peculiarity
      makes it particularly useful, in combination with diluted Russel viper venom time
      (dRVVT), for large-scale screening tests on LA.

PMID- 11342206
TI  - Differential antiplatelet effects of various glycoprotein IIb-IIIa antagonists.
AB  - The blockade of platelet glycoprotein IIb-IIIa (GPIIb-IIIa) was recently
      introduced as a new antiplatelet strategy. At present, various GPIIb-IIIa
      inhibitors are available to treat patients with acute coronary syndrome or when
      undergoing percutaneous coronary interventions. The current study systematically
      evaluates the antiplatelet effects of GPIIb-IIIa inhibitors in clinical use.
      Using conformation-dependent monoclonal antibodies [ligand-induced binding sites
      (LIBS-1), PMI-1] and flow cytometry, we showed that the GPIIb-IIIa antagonists
      abciximab, integrelin, lamifiban, and tirofiban, but not EMD 122347 or YM 337,
      induced LIBS activity of platelet GPIIb-IIIa. The LIBS activity of GPIIb-IIIa
      antagonists correlates with a proaggregatory response of fixed platelets
      pretreated with GPIIb-IIIa antagonists (intrinsic activity). All tested GPIIb
      IIIa antagonists completely inhibit concentration-dependent ADP (20 micromol/l)
      induced aggregation. In contrast, substantial TRAP (25 micromol/l)-induced
      platelet aggregation still occurs even at high inhibitor concentrations of the
      tested GPIIb-IIIa antagonists. In addition, we show that GPIIb-IIIa antagonists
      are poor inhibitors of platelet release reaction (ATP and P-selectin secretion)
      especially when strong agonists such as TRAP are used to activate platelets.
      Inhibition of platelet procoagulant activity (thrombin generation) by GPIIb-IIIa
      antagonists is dependent on the type and concentration of antagonists and on the
      strength of stimulus (thrombin, tissue factor) used to induce platelet-dependent
      thrombin generation. The present data show that significant pharmacological
      differences exist between GPIIb-IIIa antagonists that may have consequences for
      antithrombotic strategies and for future drug development.

PMID- 11342207
TI  - Characterization of whole blood aggregation with a new type of aggregometer by a
      screen filtration pressure method.
AB  - A new type of platelet aggregometer of whole blood, based on the screen
      filtration pressure method, has been developed and characterized. It measures
      resistance of flow of whole blood samples through a screen of microsieve with 30
      microm(2) openings and provides pressure rate as an index of platelet
      aggregation. On optical microscopic observation, platelet aggregates, but not
      fibrin fibers, were found to be trapped on microsieves, and the pressure rate and
      protein amounts on microsieves are correlated. The aggregometer showed good
      reproducibility for investigations performed on different days. The time course
      of pressure rates indicated a bell curve change, where the pressure rate was very
      low immediately after blood collection and gradually increased up to 60 min
      thereafter. Use of the aggregometer was able to confirm that orally administered
      aspirin inhibits ADP- and collagen-induced whole blood aggregation as well as
      platelet aggregation. The results suggest that this platelet aggregometer might
      be useful in research and clinical diagnosis of thrombotic diseases.

PMID- 11342208
TI  - Association of whole blood aggregation response with immunogold-labeled
      glycoproteins in adult and neonatal platelets.
AB  - A growing body of recent data has provided specifics about the hemostatic system
      in infants, emphasizing differences from adults. Although platelet structure in
      newborns and adults appears to be quite similar, precise information about
      platelets in the first week of life indicates functional hyporeactiveness. This
      study was designed with a twofold purpose: one was to determine if aggregation
      results corresponded to immunogold-labeled activation markers; the second was to
      use immunogold labeling to determine if infant platelets circulate in an
      activated state. The results showed significant differences in ristocetin (P =
      .03) and collagen (P = .003) impedance, and whole blood aggregation lag times in
      infants when compared to adults. Treatment of neonatal platelets with collagen
      yielded decreased ATP release compared with adults. Immunogold labeling of
      specific activation markers CD62 (P-selectin) and CD63 (GP53) revealed that
      neonatal platelets were not circulating in an activated state. Significant (P =
      .04) anti-CD41 (GPIIb) immunogold labeling differences were observed after
      thrombin stimulation, with adults binding more particles. These data suggest that
      hyporeactivity of neonatal platelets is not due to a circulating preactivated
      state, but instead may be a consequence of impaired intracellular signaling that
      affects both aggregation and membrane activation labeling. Whether this signaling
      is secondary to an intrinsic neonatal alteration or a maternal (in utero)
      environmental effect is yet to be determined.

PMID- 11342209
TI  - An unknown FVIII-inactivating substance derived from endothelial cells inhibits
      the intrinsic tenase complex.

PMID- 11342210
TI  - Confirmation of mendelian properties of heterodimeric fibrinogen molecules in a
      heterozygotic dysfibrinogenemia, "fibrinogen Amarillo," using gprphoresis to
      differentiate semifibrin molecules from fibrinogen and fibrin.
AB  - The fibrinogen molecule consists of two sets of Aalpha, Bbeta, and gamma chains
      assembled into a bilateral disulfide linked (Aalpha, Bbeta, gamma)2 structure.
      Cleavage of the two A-fibrinopeptides (FPA, Aalpha1-16) from normal Aalpha chains
      with arginine at position 16 (RFPA) by thrombin or the venom enzyme atroxin
      transforms fibrinogen into self-aggregating fibrin monomers (alpha, Bbeta,
      gamma)(2). Mutant Aalpha16R-->H fibrinopeptide (HFPA) cannot be cleaved from
      fibrinogen by atroxin. Many studies on heterozygous dysfibrinogenemias with this
      mutation suggested that incorporation of the mutant chains into the molecules was
      ordered in a manner yielding only (1) homodimeric normal (RFPARFPA) atroxin
      coagulable molecules and (2) homodimeric abnormal (H(FPA)HFPA) atroxin
      incoagulable molecules in equal quantities. Although heterodimeric molecules
      (RFPAHFPA) could not be found in studies on the intact protein, Meh et al.
      demonstrated their existence by showing that CNBr digests of fibrinogens from
      atroxin-treated Aalpha16R-->H heterozygotic dysfibrinogenemias consistently
      yielded N-terminal fragments (NDSKs) with partially resolved electrophoretic
      bands predominantly in between the NDSKs of fibrinogen and alpha-fibrin. An
      opportunity to confirm and better quantify the heterodimers arose with the recent
      development of a method (GPRphoresis) for identifying molecules lacking only one
      FPA, which is applied here in study of a newly presenting case of an Aalpha16R-
      >H dysfibrinogenemia, "fibrinogen Amarillo." GPRphoresis uses electrophoretic
      shifts, staged with GPRP-NH(2) to separate the self-aggregating fibrin monomers
      lacking both FPAs from weakly aggregating "semifibrin" molecules lacking one FPA
      An antifibrin alpha17-23 antibody is used to measure and differentiate the
      semifibrin from fibrinogen with FPA fully intact. Applying GPRphoresis to atroxin
      digests of fibrinogen Amarillo clearly demonstrated RFPARFPA, RFPAHFPA, and
      HFPAHFPA molecules in nearly perfect Mendelian 1:2:1 proportions. In turn, the
      high levels of the semifibrin in the terminal atroxin digests provide genetic
      phenotypic evidence supporting fidelity of the GPRphoresis method.

PMID- 11342211
TI  - Transcriptional activation of bovine mimecan by p53 through an intronic DNA
      binding site.
AB  - Mimecan is a small leucine-rich proteoglycan that can occur as either keratan
      sulfate proteoglycan in the cornea or as glycoprotein in many connective tissues.
      As yet, there is no information on its transcriptional regulation. Recently we
      demonstrated the presence of eight mimecan mRNA transcripts generated by
      alternative transcription initiation, alternative polyadenylation, and
      differential splicing, all of which encode an identical protein. Here we report a
      conserved consensus p53-binding DNA sequence in the first intron of bovine and
      human mimecan genes and show that wild-type p53 binds to this sequence in vitro.
      Co-transfections of Saos-2, HeLa, NIH 3T3, and primary bovine corneal keratocytes
      with bovine mimecan promoter/luciferase reporter constructs in combination with
      p53 expression vectors activate the second mimecan promoter through the p53
      binding sequence. In addition, we show absence of mimecan expression in different
      tumors and cancer cell lines, where p53 frequently is inactivated/mutated. Thus,
      this work provides novel information that links mimecan to the p53 network.

PMID- 11342212
TI  - New epidermal keratin genes from Xenopus laevis: hormonal and regional regulation
      of their expression during anuran skin metamorphosis.
AB  - Xenopus larval keratin (XLK) was isolated by gel electrophoresis of proteins of
      tadpole skin. Screening of an expression cDNA library of tail tissues by specific
      polyclonal antibodies against XLK produced XLK cDNA (xlk). Its complete
      nucleotide and predicted amino acid sequences revealed that XLK was a new member
      of type II keratin. Screening of a cDNA library of adult Xenopus skin using an
      oligonucleotide probe which had been designed from well-conserved N-terminal
      amino acid sequences of the rod domain of type I keratin produced two cDNAs, xak
      a and xak-b, which were found to be new members of type I keratin gene. Northern
      blot analysis showed that xlk was expressed exclusively in the larval skin
      whereas xak-a and xak-b were expressed exclusively in the adult skin. Their
      expression level was regulated in a region- and metamorphic stage- dependent
      manner during larval skin development. mRNA in situ hybridization experiments
      identified the cells that expressed xlk, and xak-a and xak-b as larva- specific
      epidermal cells (skein cells and basal cells), and adult suprabasal epidermal
      cells, respectively. These three genes were found to be late responsive to
      thyroid hormone. Phylogenetic relationships of these keratins with known ones are
      discussed.

PMID- 11342213
TI  - Comparative study and prediction of DNA fragments associated with various
      elements of the nuclear matrix.
AB  - Scaffold/matrix-associated region (S/MAR) sequences are DNA regions that are
      attached to the nuclear matrix, and participate in many cellular processes. The
      nuclear matrix is a complex structure consisting of various elements. In this
      paper we compared frequencies of simple nucleotide motifs in S/MAR sequences and
      in sequences extracted directly from various nuclear matrix elements, such as
      nuclear lamina, cores of rosette-like structures, synaptonemal complex.
      Multivariate linear discriminant analysis revealed significant differences
      between these sequences. Based on this result we have developed a program,
      ChrClass (Win/NT version, ftp.bionet.nsc.ru/pub/biology/chrclass/chrclass.zip),
      for the prediction of the regions associated with various elements of the nuclear
      matrix in a query sequence. Subsequently, several test samples were analyzed by
      using two S/MAR prediction programs (a ChrClass and MAR-Finder) and a simple MRS
      criterion (S/MAR recognition signature) indicating the presence of S/MARs. Some
      overlap between the predictions of all MAR prediction tools has been found.
      Simultaneous use of the ChrClass, MRS criterion and MAR-Finder programs may help
      to obtain a more clearcut picture of S/MAR distribution in a query sequence. In
      general, our results suggest that the proportion of missed S/MARs is lower for
      ChrClass, whereas the proportion of wrong S/MARs is lower for MAR-Finder and MRS.

PMID- 11342214
TI  - Crosslinking of the complementary strands of DNA by UV light: dependence on the
      oligonucleotide composition of the UV irradiated DNA.
AB  - UV light crosslinks the complementary strands of DNA. The interstrand crosslinks
      may contribute to the biological and pathological effects that UV irradiation is
      known to bring about. Here alkaline agarose gel electrophoresis was used to
      assess the crosslinked fraction of 31 selected restriction fragments of six viral
      and plasmid DNA molecules exposed to UVC light irradiation. As many as 17
      independent experiments were performed with the particular DNA fragments to get
      sufficiently precise data suitable for quantitative analyses. The data were used
      to determine how the crosslinked fraction depended on the dinucleotide,
      trinucleotide and tetranucleotide contents of the irradiated DNA fragments. This
      analysis demonstrated that DNA conformation and/or flexibility, rather than the
      local double helix thermostability, governed the phenomenon of crosslinking. For
      example, (GA).(TC) suppressed the crosslink formation in DNA more than any
      dinucleotide composed of only G and C. In addition, (CTAG).(CTAG) promoted
      crosslinking much more than any other tetranucleotide, including e.g.
      (TATA).(TATA), whereas the closely related (CATG).(CATG) belonged among the
      tetranucleotides that most suppressed the UV light induced crosslinks between the
      complementary strands of DNA. The present data reproduced crosslinking of the
      analyzed 31 restriction fragments with a correlation coefficient exceeding 0.90.
      This result will be useful to predict crosslinking along the whole human genome.

PMID- 11342215
TI  - Identification of human and mouse HIRA-interacting protein-5 (HIRIP5), two
      mammalian representatives in a family of phylogenetically conserved proteins with
      a role in the biogenesis of Fe/S proteins.
AB  - The human HIRA protein is encoded from a region of chromosome 22q that is
      critical for the DiGeorge syndrome and the velocardiofacial syndrome. We have
      previously reported that it directly interacts with core histones, with a novel
      histone-binding protein, HIRIP3, and during mouse embryogenesis, with the
      developmentally regulated homeodomain protein Pax3, suggesting a promoter
      targeted function at the chromatin level. We here report on HIRA-interacting
      protein 5 (HIRIP5), a small acidic protein that interacted with HIRA in a double
      hybrid screen performed in yeast and in in vitro protein interaction experiments.
      HIRIP5 has highly conserved homologs in both prokaryotes and eukaryotes,
      including the NFU1 gene product which has been implicated in iron metabolism in
      mitochondria of the yeast Saccharomyces cerevisiae. By radioactive in situ
      hybridization, the HIRIP5 gene was mapped to the 2p13-p15 chromosomal region,
      separate from any region previously associated with DiGeorge syndrome.

PMID- 11342216
TI  - Sequencing, expression, characterisation and phylogeny of the ADP-dependent
      phosphofructokinase from the hyperthermophilic, euryarchaeal Thermococcus
      zilligii.
AB  - The full-length gene encoding the ADP-dependent phosphofructokinase (PFK) from
      the euryarchaeal Thermococcus zilligii was cloned, using degenerate primer
      polymerase chain reaction (PCR) combined with inverse-PCR techniques, and
      ultimately expressed in Escherichia coli. The expressed enzyme was biochemically
      characterised and found to be similar to the native enzyme for most properties
      examined. Sequence database searches suggest that this unique ADP-PFK possesses a
      limited phylogenetic distribution with homologues being found only in the other
      euryarchaeta Methanococcus jannaschii, Methanosarcina mazei and closely related
      members of the order Thermococcales. A phylogenetic analysis suggests that a
      single ancestral gene diverged to form the glucokinase and PFK lineages of this
      unique sequence family. Thus, the PFK reaction, one of the defining enzymatic
      activities of the Embden-Meyerhof pathway, can now be represented by three
      separate sequence families, the well-known PFKA family exemplified by the primary
      E. coli ATP-PFK (E.C. 2.7.1.11) and its associated ATP- and pyrophosphate
      dependent PFKs (EC.2.7.1.90), the PFKB family (E. coli PFK 2 encoded by the pfkB
      gene and its homologues) and the ADP-PFKs of the Euryarchaeota reported here.

PMID- 11342217
TI  - p53 binds to cisplatin-damaged DNA.
AB  - We have previously shown that bacterially expressed p53 protein or p53 protein
      isolated from cis-diamminedichloroplatinum II (cisplatin)-damaged cells is
      capable of binding to double-stranded platinated DNA molecules lacking any p53
      DNA binding sites. Here we report using various p53 mutants that two separate
      domains of p53 protein affect p53 binding to platinated DNA. Mutations within the
      central core of p53, the domain responsible for sequence-specific DNA binding
      activity, completely eliminated p53 binding to platinated DNA. Based on
      competition experiments p53 preferred binding to sequence-specific DNA molecules
      over platinated DNA molecules. However, p53 binding to platinated DNA molecules
      was significantly stronger than p53 interactions with DNA molecules lacking
      damage and a p53 consensus site. Finally, an antibody specific to the C-terminal
      domain of p53 (pAb421) which activates sequence-specific DNA binding activity
      inhibited p53 binding to platinated DNA. Taken together, these results suggest
      that in addition to binding to p53 DNA binding sites, p53 also interacts with
      cisplatin-damaged DNA molecules.

PMID- 11342219
TI  - Transcriptional analysis and regulation of the sigma-E gene of Streptomyces
      antibioticus.
AB  - We report here the mapping of the transcriptional start point and identification
      of the promoter for the sigE gene of Streptomyces antibioticus. Sequence analysis
      revealed a conserved genetic organization of five genes encompassing sigE in S.
      antibioticus and S. coelicolor. Upstream of sigE a number of direct repeats,
      while conserved in both species, are arranged differently. Gel shift analysis
      demonstrated binding of a component of both S. antibioticus and S. coelicolor
      crude protein extracts to a 30 bp sequence encompassing one repeat, the A-rich
      box. Deletion analysis in promoter probes showed that maximal activity of the S.
      antibioticus promoter depends upon the presence of the sequence surrounding the A
      rich box, as well as the region further upstream carrying other direct repeats.

PMID- 11342218
TI  - Enhanced activity of cloned hamster TERT gene promoter in transformed cells.
AB  - In 7,12-dimethylbenz[a]anthracene-treated hamster pouch epithelial cells,
      telomerase activity increased within 1 week of treatment and reached a 6-7-fold
      increase within 3 weeks. To investigate this phenomenon, we have cloned and
      sequenced the hamster telomerase catalytic subunit (hamTERT) promoter. Transient
      transfection with different genomic segments upstream of the ATG translation
      initiation codon linked to the luciferase reporter gene mapped the core promoter
      within a 250 bp region. Three major transcription initiation sites and several
      minor sites were found between -42 and -140 bp relative to the ATG site. Like the
      human and murine TERT promoters, the hamTERT promoter lacks TATA and CAT boxes
      and all three promoters share similar regulatory factor binding sites. DNase I
      footprint analysis revealed six protected regions which contain sequences
      homologous with known transcription factor binding sites. Three protein binding
      regions (I, II, and III) were essential for the promoter activity. Regions I and
      III bound to Sp1 and Sp3 transcriptional factors, whereas region II bound to an
      unknown factor. Transient transfection of a promoter-luciferase plasmid into
      Drosophila SL2 cells showed that Sp1 and Sp3 regulated the hamster TERT promoter
      in a concentration-dependent and synergistic manner. Telomerase activity showed a
      2-4-fold and 8-10-fold increase in immortalized cells and tumor cells,
      respectively, but hamTERT expression was only increased 1.7-fold and 2.4-fold,
      respectively, in the same cells.

PMID- 11342220
TI  - Characterization of the human UDP-galactose:ceramide galactosyltransferase gene
      promoter.
AB  - UDP-galactose:ceramide galactosyltransferase (CGT, EC 2.4.1.45) is a key enzyme
      in the biosynthesis of galactocerebroside, the most abundant glycosphingolipid in
      the myelin sheath. An 8 kb fragment upstream from the transcription initiation
      site of CGT gene was isolated from a human genomic DNA library. Primer extension
      analysis revealed a single transcription initiation site 329 bp upstream from the
      ATG start codon. Neither a consensus TATA nor a CCAAT box was identified in the
      proximity to the transcription start site; however, this region contains a high
      GC content and multiple putative regulatory elements. To investigate the
      transcriptional regulation of CGT, a series of 5' deletion constructs of the 5'
      flanking region were generated and cloned upstream from the luciferase reporter
      gene. By comparing promoter activity in the human oligodendroglioma (HOG) and
      human neuroblastoma (LAN-5) cell lines, we found that the CGT promoter functions
      in a cell type-specific manner. Three positive cis-acting regulatory regions were
      identified, including a proximal region at -292/-256 which contains the potential
      binding sites for known transcription factors (TFs) such as Ets and SP1 (GC box),
      a distal region at -747/-688 comprising a number of binding sites such as the ERE
      half-site, NF1-like, TGGCA-BP, and CRE, and a third positive cis-acting region
      distally localized at -1325/-1083 consisting of binding sites for TFs such as
      nitrogen regulatory, TCF-1, TGGCA-BP, NF-IL6, CF1, bHLH, NF1-like, GATA, and
      gamma-IRE. A negative cis-acting domain localized in a far distal region at 
      1594/-1326 was also identified. Our results suggest the presence of both positive
      and negative cis-regulatory regions essential for the cell-specific expression in
      the TATA-less promoter of the human CGT gene.

PMID- 11342221
TI  - Molecular cloning and analysis of the 5'-flanking region of the human MYPT1 gene.
AB  - We have cloned and sequenced a 5 kb genomic fragment in the 5'-flanking region of
      the human myosin phosphatase target subunit 1. The transcription initiation site
      (+1) was 268 bp upstream from the translation start site. In this promoter there
      are no canonical TATA or CAAT box elements but there is a high GC-rich sequence.
      Basal promoter activity was due to the GC-rich region that contained one Sp1
      transcription factor binding site, thus demonstrating that the MYPT1 gene is a
      housekeeping gene. Luciferase reporter assays showed the presence of two regions
      for positive elements and one for a negative element.

PMID- 11342222
TI  - Genomic structure and promoter activity of the human tissue factor pathway
      inhibitor-2 gene.
AB  - Human type-2 tissue factor pathway inhibitor (TFPI-2), also known as placental
      protein 5, is a 32 kDa serine proteinase inhibitor consisting of three tandemly
      arranged Kunitz-type inhibitor domains homologous to tissue factor pathway
      inhibitor. TFPI-2 strongly inhibits a wide variety of serine proteinases
      including trypsin, chymotrypsin, plasmin, kallikrein and blood coagulation factor
      XIa. In this study, we have isolated and characterized a genomic clone from an
      artificial chromosome genomic library that encodes the entire human TFPI-2 gene.
      The human TFPI-2 gene spans approximately 7 kb and consists of five exons and
      four introns. Each Kunitz-type domain is encoded by a single exon, similar to
      that observed for murine TFPI-2 and other Kunitz-type proteinase inhibitors. A
      total of 535 bp of the 3'-flanking region contain two probable polyadenylation
      sites (AATAAA) at +4297 and +4314. A single transcription initiation site was
      identified by oligo-capping and reverse transcription-PCR analysis. Transient
      transfection of reporter plasmids containing segments of the 5'-flanking region
      into human transformed bone marrow endothelial cells and glioblastoma cells
      identified an 85 bp region (-224 to -139) sufficient for transcription of the
      human TFPI-2 gene.

PMID- 11342223
TI  - Characterization and transcriptional analysis of Pseudomonas fluorescens
      denitrifying clusters containing the nar, nir, nor and nos genes.
AB  - In this study, we report the cloning and characterization of denitrifying gene
      clusters of Pseudomonas fluorescens C7R12 containing the narXLDKGHJI, nirPOQSM,
      norCB and nosRZDFYL genes. While consensus sequences for Fnr-like protein binding
      sites were identified in the promoter regions of the nar, nir, nor and nos genes,
      consensus sequences corresponding to the NarL binding sites were identified only
      upstream the nar genes. Monitoring by mRNA analysis the expression of the narG,
      nirS, norB and nosZ structural genes suggests a sequential induction of the
      denitrification system in P. fluorescens.

PMID- 11342224
TI  - Identification of SCAN dimerization domains in four gene families.
AB  - Zinc-finger transcription factors are often accompanied by modular sequence
      motifs such as the Kruppel-associated box (KRAB) and the SCAN domain. The KRAB
      domain mediates transcriptional repression while the SCAN domain mediates
      selective protein dimerization. The hypoalphalipoproteinemia susceptibility gene
      ZNF202 encodes a SCAN box and a KRAB domain followed by eight Cys2-His2 zinc
      finger motifs. In order to identify the existence of genes which encode proteins
      of structural homology to ZNF202, a mouse lambda library was screened with a
      human ZNF202 cDNA probe. The isolated cDNA clones represented three SCAN-domain
      encoding gene families. We purified three novel cDNAs that encode a SCAN-KRAB
      (Cys2-His2)x domain alignment and one cDNA that encodes a SCAN-(Cys2-His2)x
      domain alignment. In addition, we identified one cDNA sequence with a predicted
      protein sequence containing a KRAB-SCAN-KRAB-(Cys2-His2)x domain alignment.
      Therefore, when combined with the recently discovered family of isolated SCAN
      domain-encoding genes, four SCAN domain gene families can be distinguished. The
      consensus sequences for the murine SCAN and KRAB domains are highly conserved
      within the mammalian phylogenetic tree which may be useful in elucidating the
      biological function of these protein modules and the crucial residues responsible
      for their binding specificity.

PMID- 11342225
TI  - Identification of the human crooked neck gene by comparative gene identification.
AB  - Drosophila melanogaster serves as a useful model organism for functional genomic
      studies, and its genome project was recently completed. We previously described a
      comparative-gene-identification approach to assist human ortholog gene
      identification that involves applying an entire proteome as an alignment
      template. Analysis of the available 14100 Drosophila protein sequences revealed
      that 37% of them (5228 sequences) might lead to discoveries of novel human genes.
      Upon further database interrogations, we found several putative full-length human
      gene transcripts, including the human crooked neck (crn) gene. Based on sequence
      gap-closure experiments using reverse transcriptase-polymerase chain reaction as
      well as bioinformatic analysis, we found that the assembled human cDNA contig of
      crooked neck gene was at least 3903 base pairs in length with alternative
      splicing variations which encoded mainly for a 687-amino-acid residue protein.
      The human crooked neck gene was located on chromosome 20 with at least 15 exons.
      The unique features of the 16 copies of the tetratrico peptide repeat (TPR) motif
      were conserved in the yeast, fly and human crooked neck orthologous proteins,
      which were important for spliceosome assembly in cells.

PMID- 11342226
TI  - Identification of a murine cysteinyl leukotriene receptor by expression in
      Xenopus laevis oocytes.
AB  - We report the identification of an EST encoding a murine cysteinyl leukotriene
      (mCysLT) receptor. LTD4, LTC4 and LTE4 but not LTB4 or various nucleotides
      activated Ca2+-evoked Cl- currents in mCysLT1 expressing Xenopus laevis oocytes.
      The response to LTD4 was blocked by MK-571, reduced by pretreatment with
      pertussis toxin (PTX), and was partly dependent on extracellular Ca2+. The
      identified murine CysLT1 receptor differs from the hCysLT1 receptor with regard
      to PTX sensitivity, receptor-mediated Ca2+ influx, and antagonist sensitivity.

PMID- 11342227
TI  - Identification of a novel fibroblast growth factor, FGF-22, preferentially
      expressed in the inner root sheath of the hair follicle.
AB  - We isolated cDNA encoding a novel fibroblast growth factor (FGF-22) (170 amino
      acids) from human placenta. Of the FGF family members, FGF-22, which appears to
      be a secreted protein, is most similar to FGF-10 and FGF-7 (approximately 46% and
      approximately 40% amino acid identities, respectively). The human FGF-22 gene was
      localized on chromosome 19p13.3. We also isolated mouse cDNA encoding FGF-22 (162
      amino acids) from the skin. Mouse FGF-22 shows high homology (87% amino acid
      identity) to human FGF-22. Mouse FGF-22 mRNA was found to be preferentially
      expressed in the skin among the mouse adult tissues examined by Northern blotting
      analysis. By in situ hybridization, FGF-22 mRNA in the skin was found to be
      preferentially expressed in the inner root sheath of the hair follicle.
      Therefore, FGF-22 is expected to be a unique FGF that plays a role in hair
      development.

PMID- 11342228
TI  - Identification of eight novel 5'-exons in cerebral capillary malformation gene-1
      (CCM1) encoding KRIT1.
AB  - Truncating mutations in the CCM1 gene encoding KRIT1 were recently found in
      patients affected by inherited cerebral capillary malformations, lesions that
      cause a wide variety of neurologic problems. However, CCM1 mutations have not
      been identified in all the families linked to CCM1. Here we demonstrate that the
      CCM1 gene contains eight additional exons which may thus encompass the missing
      mutations.

PMID- 11342230
TI  - The NBA First-Round Draft.

PMID- 11342229
TI  - cDNA cloning and expression of swine IL-7 from neonatal intestinal epithelium.
AB  - Swine IL-7 (sIL-7) cDNA has been isolated from neonatal intestinal epithelium by
      reverse transcription polymerase chain reaction (RT-PCR) with designated primers
      based on the conserved sequences of the other mammalian IL-7. Recombinant sIL-7
      was able to induce the bone marrow cell proliferation like human IL-7. The
      complete open reading frame contains 531 bp coding deduced 176 amino acid
      residues, with a calculated molecular mass of 20.1 kDa. The observed similarity
      between swine and human IL-7 sequences (66% identical and 89% conserved) suggests
      that a study on the immune responses correlated with IL-7 in the gut of swine
      will be valuable to understand their mechanisms in human. By RT-PCR using the
      constructed specific primers to sIL-7, sIL-7 mRNA was confirmed to be expressed
      in swine intestine, thymus, kidney and skin but not in the heart.

PMID- 11342231
TI  - "The Vulvar Mass in the Prepubertal Child"

PMID- 11342234
TI  - Halogenated 2,5-pyrrolidinediones: synthesis, bacterial mutagenicity in Ames
      tester strain TA-100 and semi-empirical molecular orbital calculations.
AB  - The chloroimide 3,3-dichloro-4-(dichloromethylene)-2,5-pyrrolidinedione, a
      tetrachloroitaconimide, is the principal mutagen produced by chlorination of
      simulated poultry chiller water. It is the second most potent mutagenic
      disinfection by-product of chlorination ever reported. Six of seven new synthetic
      analogs of this compound are direct-acting mutagens in Ames tester strain TA-100.
      Computed energies of the lowest unoccupied molecular orbital (E(LUMO)) and of the
      radical anion stability (DeltaH(f)(rad)-DeltaH(f)) from MNDO-PM3 for the
      chloroimides show a quantitative correlation with the Ames TA-100 bacterial
      mutagenicity values. The molar mutagenicities of these direct acting mutagenic
      imides having an exocyclic double bond fit the same linear correlation (lnM(m)
      vs. E(LUMO); lnM(m) vs. DeltaH(f)(rad)--DeltaH(f)) as the chlorinated 2(5H)
      furanones, including the potent mutagen MX, 3-chloro-4-(dichloro-methyl)-5
      hydroxy-2(5H)-furanone, a by-product of water chlorination and paper bleaching
      with chlorine. Mutagenicity data for related haloimides having endocyclic double
      bonds are also given. For the same number of chlorine atoms, the imides with
      endocyclic double bonds have significantly higher Ames mutagenicity compared to
      their structural analogs with exocyclic double bonds, but do not follow the same
      E(LUMO) or DeltaH(f)(rad)-DeltaH(f) correlation as the exocyclic chloroimides and
      the chlorinated 2(5H)-furanones.

PMID- 11342235
TI  - Genotoxic ability of cadmium, chromium and nickel salts studied by kinetochore
      staining in the cytokinesis-blocked micronucleus assay.
AB  - The aneugenic and clastogenic ability of cadmium chloride(II), cadmium
      sulfate(II), nickel chloride(II), nickel sulfate(II), chromium chloride(III) and
      potassium dichromate(IV) have been evaluated through kinetochore-stained
      micronucleus test. Traditional genotoxicity assays evaluate DNA damage, gene
      mutations and chromosome breakage. However, these tests are not adequate to
      detect aneugenic agents that do not act directly on DNA. Staining kinetochores in
      the cytokinesis-blocked micronucleus assay is a useful way to discriminate
      between clastogens and aneuploidogens and may allow a rapid identification of
      aneuploidy-inducing environmental compounds. Human diploid fibroblasts (MRC-5)
      were employed. All compounds increased micronuclei frequency in a statistically
      significant way. However, increases in kinetochore-positive micronuclei
      frequencies were higher than in kinetochore-negative ones. The present work
      demonstrates the genotoxic ability of the cadmium and chromium salts studied.
      Aneugenic as well as clastogenic ability could be observed with this assay.
      Nickel salts, as it was expected because of their known weak mutagenicity, showed
      lower genotoxic effects than the other metal salts studied. As the test employed
      only allows the detection of malsegregation, it is proposed that this mechanism
      is at least one of those by which the tested metal salts induced aneuploidy. On
      the other hand, visualization of kinetochores in all experiments suggests that
      the compounds studied did not act by damaging these structures.

PMID- 11342236
TI  - Chromosome aberrations and sister chromatid exchanges in cultured human
      lymphocytes treated with sodium metabisulfite, a food preservative.
AB  - The aim of this study was to investigate the ability of sodium metabisulfite
      (SMB) which is used as an antimicrobial substance in food, to induce chromosome
      aberrations (CA) and sister chromatid exchanges (SCE) in human lymphocytes. SMB
      induced CAs and SCEs at all concentrations (75, 150 and 300 microg/ml) and
      treatment periods (24 and 48h) dose-dependently. However, SMB decreased the
      replication index (RI) and the mitotic index (MI) at the concentrations of 150
      and 300 microg/ml for 24 and 48h treatment periods. This decrease was dose
      dependent as well.

PMID- 11342237
TI  - SeO(2) induces apoptosis with down-regulation of Bcl-2 and up-regulation of P53
      expression in both immortal human hepatic cell line and hepatoma cell line.
AB  - An immortal human hepatic cell line HL-7702 and human hepatoma cell line SMMC
      7721 were treated with 3-30 microM SeO(2). SeO(2) at 30 microM markedly inhibited
      cell proliferation and viability, and prompted apoptosis of both normal hepatic
      and hepatoma cells after 48h treatment. SeO(2) could also down-regulate the Bcl-2
      level, greatly in HL-7702 and slightly in SMMC-7721 cells, but up-regulate wild
      type P53 level a little in HL-7702 and significantly in SMMC-7721 cells. The Bcl
      2/P53 value was closely correlated with the apoptotic rate as well as SeO(2)
      concentrations.

PMID- 11342238
TI  - Assessment of DNA strand breakage by comet assay in diabetic patients and the
      role of antioxidant supplementation.
AB  - Diabetes patients often show increased production of reactive oxidative species
      (ROS) together with vascular complications. The presence of these ROS may lead to
      increased DNA damage in peripheral blood lymphocytes that may be revealed by the
      comet assay. To test whether DNA is damaged in diabetes, peripheral blood samples
      were taken from 30 control individuals and 63 diabetic patients (15 insulin
      dependent (IDDM) and 48 non-insulin dependent (NIDDM)) and the alkaline comet
      assay was used to evaluate background levels of DNA damage. Significant
      differences were detected between control and diabetic patients in terms of
      frequencies of damaged cells. The extend of DNA migration was greater in NIDDM
      patients by comparison with IDDM patients which might indicate that IDDM patients
      are handling more oxidative damage on a regular basis. Smoker individuals had
      higher frequencies of cells with migration by comparison with the non-smokers in
      both groups. Also, clear differences between patients on placebo and on Vitamin E
      supplementation for 12 weeks were observed on the basis of the extend of DNA
      migration during single cell gel electrophoresis.

PMID- 11342239
TI  - Oxidative mutagenesis of doxorubicin-Fe(III) complex.
AB  - Doxorubicin has a high affinity for inorganic iron, Fe(III), and has potential to
      form doxorubicin-Fe(III) complexes in biological systems. Indirect involvement of
      iron has been substantiated in the oxidative mutagenicity of doxorubicin. In this
      study, however, direct involvement of Fe(III) was evaluated in mutagenicity
      studies with the doxorubicin-Fe(III) complex. The Salmonella mutagenicity assay
      with strain TA102 was used with a pre-incubation step. The highest mutagenicity
      of doxorubicin-Fe(III) complex was observed at the dose of 2.5nmol/plate of the
      complex. The S9-mix decreased this highest mutagenicity but increased the number
      of revertants at a higher dose of 10nmol/plate of the complex. On the other hand,
      the mutagenicity of the doxorubicin-Fe(III) complex at the doses of 0.25, 0.5, 1
      and 2nmol/plate was enhanced about twice by the addition of glutathione plus
      H(2)O(2). This enhanced mutagenicity as well as of the complex itself, the
      complex plus glutathione, and the complex plus H(2)O(2) were reduced by the
      addition of ADR-529, an Fe(III) chelator, and potassium iodide, a hydroxyl
      radical scavenger. These results indicate that doxorubicin-Fe(III) complex exert
      the mutagenicity through oxidative DNA damage and that Fe(III) is a required
      element in the mutagenesis of doxorubicin.

PMID- 11342240
TI  - Genotoxicity assessment in aquatic environments under the influence of heavy
      metals and organic contaminants.
AB  - The genotoxicity of river water and sediment including interstitial water was
      evaluated by microscreen phage-induction and Salmonella/microsome assays.
      Different processes used to fractionate the sediment sample were compared using
      solvents with different polarities. The results obtained for mutagenic activity
      using the Salmonella/microsome test were negative in the water and interstitial
      water samples analysed using the direct concentration method. The responses in
      the microscreen phage-induction assay showed the presence of genotoxic or
      indicative genotoxic activity for at least one water sample of each site analysed
      using the same concentration method. Similar results were obtained for
      interstitial water samples, i.e. absence of mutagenic activity in the
      Salmonella/microsome test and presence of genotoxic activity in the microscreen
      phage-induction assay. Metal contamination, as evidenced by the concentrations in
      stream sediments, may also help explain some of these genotoxic results. Stream
      sediment organic extracts showed frameshift mutagenic activity in the ether
      extract detected by Salmonella/microsome assay. The concentrates evaluated by
      microscreen phage-induction assay identified the action of organic compounds in
      the non-polar, medium polar and polar fractions. Thus, the microscreen phage
      induction assay has proven to be a more appropriate methodology than the
      Salmonella/microsome test to analyse multiple pollutants in this ecosystem where
      both organic compounds and heavy metals are present.

PMID- 11342241
TI  - Monitoring airborne genotoxicants in the rubber industry using genotoxicity tests
      and chemical analyses.
AB  - This research was designed to examine the presence of mutagenic/carcinogenic
      compounds in airborne pollutants in the rubber industry using an integrated
      chemical/biological approach. Inhalable airborne particulate matter (PM-10: <10
      microm) was collected in four rubber factories using a high-volume sampler
      equipped with a cascade impactor for particle fractionation. The organic extracts
      of two different fractions (0.5-10 microm and <0.5 microm) were examined for
      mutagenicity with the Ames test and for in vitro DNA-damaging activity in human
      leukocytes by single-cell microgel electrophoresis (Comet assay). The extracts
      were also studied by gas chromatography/mass spectrometry (GC/MS) for polycyclic
      aromatic hydrocarbon (PAH) content. Nitrosamines in ambient air were sampled on
      cartridges and analysed by GC with a thermal energy analyser (TEA) detector.
      Airborne volatile genotoxins were monitored in situ using a clastogenicity plant
      test (Tradescantia/micronuclei test). The results showed that airborne
      particulates were mainly very fine (<0.5 microm) and that trace amounts of
      genotoxic nitrosamines (N-nitrosodimethylamine: 0.10-0.98 microg/m(3); N
      nitrosomorpholine: 0.77-2.40 microg/m(3)) and PAH (total PAH: 0.34-11.35
      microg/m(3)) were present in air samples. Some extracts, particularly those
      obtained from the finest fractions, were mutagenic with the Ames test and
      genotoxic with the Comet assay. In situ monitoring of volatile mutagens using the
      Tradescantia/micronuclei test gave positive results in two working environments.
      The results showed the applicability of this integrated chemical-biological
      approach for detecting volatile and non-volatile genotoxins and for monitoring
      genotoxic hazards in the rubber industry.

PMID- 11342242
TI  - Frequencies of chromosome aberrations in a control population determined by G
      banding.
AB  - Control data on chromosome aberration frequencies determined by G banding from
      several studies undertaken in this laboratory have been re-analysed in relation
      to age and smoking. The combined study group comprised a total of 162 men (90 non
      smokers and 72 smokers) with ages ranging from 20 to 72 years. For the group as a
      whole, significant increases were observed in translocations and all symmetrical
      exchanges with increasing age and also when smokers were compared with non
      smokers.

PMID- 11342243
TI  - Analysis of chromosomal aberrations in men occupationally exposed to cement dust.
AB  - Cement industry is considered as a major pollution problem on account of dust and
      particulate matter emitted at various steps of cement manufacture. Cement dust
      consists of many toxic constituents. The workers who are employed in cement
      industries are exposed to cement dust for long periods. Therefore, it is
      mandatory to evaluate the mutagenic effects of occupational exposure to cement
      dust in such workers. In the present study, we analyzed the samples of 124 male
      workers including 59 smokers and 65 non-smokers who were employed in cement
      industry for a period of 1-17 years. For comparison, 106 controls (including 47
      smokers and 59 non-smokers) of the same age group and socio-economic status were
      also studied. Controls had no exposure to cement dust or any known physical or
      chemical agent. A significant increase in the incidence of chromosomal
      aberrations was observed in the exposed group when compared to the control group.
      The results were analyzed separately for non-smokers and smokers. The chromosomal
      damage was more pronounced in the smokers when compared with the non-smokers both
      in control and exposed groups. A significant increase in the frequency of
      chromosomal aberrations was also observed with increase in age in both control
      and exposed subjects.

PMID- 11342244
TI  - Gamma ray induced DNA damage in human and mouse leucocytes measured by SCGE-Pro:
      a software developed for automated image analysis and data processing for Comet
      assay.
AB  - The studies reported in this communication had two major objectives: first to
      validate the in-house developed SCGE-Pro: a software developed for automated
      image analysis and data processing for Comet assay using human peripheral blood
      leucocytes exposed to radiation doses, viz. 2, 4 and 8 Gy, which are known to
      produce DNA/chromosome damage using alkaline Comet assay. The second objective
      was to investigate the effect of gamma radiation on DNA damage in mouse
      peripheral blood leucocytes using identical doses and experimental conditions,
      e.g. lyses, electrophoretic conditions and duration of electrophoresis which are
      known to affect tail moment (TM) and tail length (TL) of comets. Human and mouse
      whole blood samples were irradiated with different doses of gamma rays, e.g. 2, 4
      and 8 Gy at a dose rate of 0.668Gy/min between 0 and 4 degrees C in air. After
      lyses, cells were electrophorased under alkaline conditions at pH 13, washed and
      stained with propidium iodide. Images of the cells were acquired and analyzed
      using in-house developed imaging software, SCGE-Pro, for Comet assay. For each
      comet, total fluorescence, tail fluorescence and tail length were measured.
      Increase in TM and TL was considered as the criteria of DNA damage. Analysis of
      data revealed heterogeneity in the response of leucocytes to gamma ray induced
      DNA damage both in human as well as in mouse. A wide variation in TM and TL was
      observed in control and irradiated groups of all the three donors. Data were
      analyzed for statistical significance using one-way ANOVA. Though a small
      variation in basal level of TM and TL was observed amongst human and mouse
      controls, the differences were not statistically significant. A dose-dependent
      increase in TM (P<0.001) and TL (P<0.001) was obtained at all the radiation doses
      (2-8 Gy) both in human and mouse leucocytes. However, there was a difference in
      the nature of dose response curves for human and mouse leucocytes. In human
      leucocytes, a linear increase in TM and TL was observed up to the highest
      radiation dose of 8 Gy. However, in case of mouse leucocytes, a sharp increase in
      TM and TL was observed only up to 4 Gy, and there after saturation ensued. In
      human samples, the dose response of both TM and TL showed best fits with linear
      model (r(TM)=0.999 and r(TL)=0.999), where as in mouse, the best fit was obtained
      with Sigmoid (Boltzman) model. From the present data on leucocytes with increase
      in TM and TL as the criteria of DNA damage, it appears that mouse is relatively
      more sensitive to radiation damage than humans.

PMID- 11342245
TI  - Mutagenicity of bisphenol A and its suppression by interferon-alpha in human RSa
      cells.
AB  - Bisphenol A is used as a monomer in the production of polycarbonate plastic
      products. The widespread use of bisphenol A has raised concerns about its effects
      in humans. Since there is little information on the mutagenic potential of the
      chemical, the mutagenicity of bisphenol A was tested using human RSa cells, which
      has been utilized for identification of novel mutagens. In genomic DNA from cells
      treated with bisphenol A at concentrations ranging from 1x10(-7) to 1x10(-5)M,
      base substitution mutations at K-ras codon 12 were detected using PCR and
      differential dot-blot hybridization with mutant probes. Mutations were also
      detected using the method of peptide nucleic acid (PNA)-mediated PCR clamping.
      The latter method enabled us to detect the mutation in bisphenol A-treated cells
      at a dose (1x10(-8)M) equivalent to that typically found in the environment.
      Induction of ouabain-resistant (Oua(R)) phenotypic mutation was also found in
      cells treated with 1x10(-7) and 1x10(-5)M of bisphenol A. The induction of K-ras
      codon 12 mutations and Oua(R) mutations was suppressed by pretreating RSa cells
      with human interferon (HuIFN)-alpha prior to bisphenol A treatment. The cells
      treated with bisphenol A at the concentration of 1x10(-6)M elicited unscheduled
      DNA synthesis (UDS). These findings suggested that bisphenol A has mutagenicity
      in RSa cells as well as mutagens that have been tested in these cells, and
      furthermore, that a combination of the PNA-mediated PCR clamping method with the
      human RSa cell line may be used as an assay system for screening the mutagenic
      chemicals at very low doses.

PMID- 11342246
TI  - Detection of DNA damage in haemocytes of zebra mussel using comet assay.
AB  - The aim of the study was to use the comet assay on haemocytes of freshwater
      mussel, Dreissena polymorpha Pallas, for detection of possible DNA damage after
      exposure to pentachlorophenol (PCP) and to evaluate the potential application of
      the comet assay on mussel haemocytes for genotoxicity monitoring of freshwater
      environment. Zebra mussels were exposed for seven days to different
      concentrations (10, 80, 100, 150 microg/l) of PCP and in the river Sava
      downstream from Zagreb municipal wastewater outlet. Significant increase in DNA
      damage was observed after exposure to PCP at doses of 80 microg/l and higher and
      after in situ exposure in the river Sava as well. This study confirmed that the
      comet assay applied on zebra mussel haemocytes may be a useful tool in
      determining the potential genotoxicity of water pollutants.

PMID- 11342247
TI  - Novel functions of complex carbohydrates elucidated by the mutant mice of
      glycosyltransferase genes.
AB  - Complex carbohydrates consist of carbohydrate moieties and protein or lipid
      portions, resulting in the formation of glycoproteins, proteoglycans or
      glycosphingolipids. The polymorphic carbohydrate structures are believed to
      contain profound biological implications which are important in cell-cell or cell
      extracellular matrix interactions. A number of studies to delineate the roles of
      carbohydrates have been performed, and demonstrated definite changes in their
      profiles, cellular phenotypic changes or, sometimes, morphological and functional
      changes in tissues after modification of their structures. Recent successes in
      the isolation of glycosyltransferase genes and their modification enzyme genes
      has enabled clearer demonstrations of the roles of complex carbohydrates. In
      particular, genetic modification of glycosyltransferase genes in mice can
      elucidate the biological significances of their products in vivo. Here, we
      summarize recent advances in the understanding of the roles of complex
      carbohydrates provided from studies of gene knock-out mice of glycosyltransferase
      and modification enzyme genes focusing on novel functions which had not been
      expected.

PMID- 11342248
TI  - Occurrence of an unusual phosphorylated N-acetyllactosamine in horse colostrum.
AB  - The colostrum of horses (thoroughbreds) was extracted and fractionated to yield
      Gal(beta1-4)GlcNAcalpha1-phosphate, which has not previously been detected in any
      mammalian milk or colostrum, as well as Neu5Ac(alpha2-3)Gal(beta1-4)Glc. The
      structures of these saccharides were established by NMR spectroscopy and MALDI
      TOF mass spectrometry.

PMID- 11342249
TI  - An extracellular beta-galactofuranosidase from Aspergillus niger and its use as a
      tool for glycoconjugate analysis.
AB  - Aspergillus niger produces an extracellular beta-galactofuranosidase, which can
      specifically hydrolyse beta-D-galactofuranose (Galf) from glycoconjugates. The
      production of this enzyme can be induced by the addition of a Galf-containing A.
      niger mycelial wall extract. However, on other carbon sources accumulation
      occurred only during the starvation conditions of the late stationary phase.
      Extracellular glucoamylases from this stage of cultivation possessed
      significantly lower levels of Galf than those from the earlier exponential growth
      phase when beta-galactofuranosidase is absent, suggesting in situ beta
      galactofuranosidic hydrolysis. The beta-galactofuranosidase responsible was
      subsequently purified to homogeneity and characterised. It is a glycoprotein of
      90 kDa (determined by SDS-PAGE) with activity against beta-linked Galf residues,
      with a Km of 4 mM against p-nitrophenyl-beta-D-galactofuranoside and a pH optimum
      of 3-4. The preparation did not contain other contaminating glycosidase
      activities; p-nitrophenyl-beta-D- and -alpha-D-galactopyranose, and alpha-D
      methyl-Galf were not hydrolysed. Results are presented to show that this enzyme
      could be employed as a useful tool for the analysis of glycoconjugates containing
      biologically important Galf components.

PMID- 11342250
TI  - An investigation of the action of porcine pancreatic alpha-amylase on native and
      gelatinised starches.
AB  - The action of pancreatic alpha-amylase (EC 3.2.1.1) on various starches has been
      studied in order to achieve better understanding of how starch structural
      properties influence enzyme kinetic parameters. Such studies are important in
      seeking explanations for the wide differences reported in postprandial glycaemic
      and insulinaemic indices associated with different starchy foodstuffs. Using
      starches from a number of different sources, in both native and gelatinised
      forms, as substrates for porcine alpha-amylase, we showed by enzyme kinetic
      studies that adsorption of amylase to starch is of kinetic importance in the
      reaction mechanism, so that the relationship between reaction velocity and enzyme
      concentration [E0] is logarithmic and described by the Freundlich equation.
      Estimations of catalytic efficiencies were derived from measurements of kcat/Km
      performed with constant enzyme concentration so that comparisons between
      different starches were not complicated by the logarithmic relationship between
      E0 and reaction velocity. Such studies reveal that native starches from normal
      and waxy rice are slightly better substrates than those from wheat and potato.
      After gelatinisation at 100 degrees C, kcat/Km values increased by 13-fold (waxy
      rice) to 239-fold (potato). Phosphate present in potato starch may aid the
      swelling process during heating of suspensions; this seems to produce a very
      favourable substrate for the enzyme. Investigation of pre-heat treatment effects
      on wheat starch shows that the relationship between treatment and kcat/Km is not
      a simple one. The value of kcat/Km rises to reach a maximum at a pre-treatment
      temperature of 75 degrees C and then falls sharply if the treatment is conducted
      at higher temperatures. It is known that amylose is leached from starch granules
      during heating and dissolves. On cooling, the dissolved starch is likely to
      retrograde and become resistant to amylolysis. Thus the catalytic efficiency
      tends to fall. In addition, we find that the catalytic efficiency on the
      different starches varies inversely with their solubility and we interpret this
      finding on the assumption that the greater the solubility, the greater is the
      likelihood of retrogradation. We conclude that although alpha-amylase is present
      in high activity in digestive fluid, the enzymic hydrolysis of starch may be a
      limiting factor in carbohydrate digestion because of factors related to the
      physico-chemical properties of starchy foods.

PMID- 11342251
TI  - Gossypol isomers bind specifically to blood plasma proteins and spermatozoa of
      rainbow trout fed diets containing cottonseed meal.
AB  - We investigated the role of gossypol isomers binding to blood plasma, seminal
      plasma and spermatozoa to elucidate gossypol anti-fertility action in the teleost
      fish, rainbow trout (Oncorhynchus mykiss). Growth and hematological indicators of
      males were depressed when fish meal protein in diets was completely replaced with
      cottonseed meal. The cottonseed meal contained equal proportions of (-) (47.8+/
      1.6%) and (+) gossypol isomers. Concentrations of spermatozoa were decreased with
      increasing proportions of gossypol in diets (from 0.22% to 0.95%); however, sperm
      motility and fertilizing ability were not affected. In contrast to mammals,
      steroid hormone concentrations were not suppressed in fish given diets with
      gradual increase of gossypol level. Gossypol concentrations were 100-fold higher
      in blood plasma than in seminal plasma, confirming a barrier in gossypol transfer
      between the general circulation and the testis. Spermatozoa accumulated
      predominantly (+) enantiomer (65-75%) with decreasing proportions as dietary
      gossypol concentrations increased. Spermatozoa bound most of the gossypol
      contained in the semen; however, this did not result in impairment of the sperm
      motility apparatus. Teleost fish sperm rely on ATP stores that accumulate during
      maturation as a source of energy during activation. In addition, the duration of
      sperm movement is short in these fish. As such, we hypothesize that the major
      action of gossypol on mammalian sperm, which is uncoupling of oxidative
      phosphorylation, does not impair the energy supply required for flagellar beating
      in fish spermatozoa.

PMID- 11342252
TI  - Interaction of enkephalin derivatives with reactive oxygen species.
AB  - The oxidation of opioid peptides by tyrosinase in the presence of an excess of a
      thiol gives rise to cysteinyldopa derivatives. The major products arising from
      the reaction between Leu-enkephalin and cysteine are represented by 5-S
      cysteinyldopaenkephalin (5-CDenk) and 2-S-cysteinyldopaenkephalin (2-CDenk). The
      interaction of 5-CDenk and 2-CDenk with reactive oxygen species (ROS) has been
      studied. These compounds are able to scavenge superoxide anion, hydroxyl and
      peroxyl radicals as well as to reduce the lipid peroxidation rate induced by
      ABAP. The scavenging activities in all instances are dose-dependent. In some
      cases CDenks are more active than compounds recognized as strong radical
      scavengers, such as Trolox and mannitol. As a result of the action of the Fenton
      system, the CDenks (as well as the Enks) are oxidized into pigmented derivatives.
      The possible implications of the interaction of CDenks and Enks with ROS on
      melanization process in Parkinson's disease are discussed.

PMID- 11342253
TI  - Comparative study of blood group-recognizing lectins toward ABO blood group
      antigens on neoglycoproteins, glycoproteins and complex-type oligosaccharides.
AB  - Binding specificities of ABO blood group-recognizing lectins toward blood group
      antigens on neoglycoproteins, glycoproteins and complex-type oligosaccharides
      were studied by lectin-blotting analysis, enzyme linked immunosorbent assay and
      lectin-conjugated agarose column chromatography. Human serum albumin conjugated
      with A- and B-trisaccharides was clearly recognized by Helix pomatia (HPA),
      Phaseolus lunatus, Dolichos biflorus agglutinins, and Griffonia simplicifolia I
      agglutinin B(4), respectively. Almost the same results were obtained for human
      group A and B ovarian cyst and A-active hog gastric mucins, but Glycine max
      agglutinin only reacted to the group A hog mucin. When human plasma von
      Willebrand factor (vWF), having Asn-linked blood group antigens, was tested, HPA
      was highly sensitive to blood group A antigen on the vWF. Ulex europaeus
      agglutinin I (UEA-I) preferentially bound to the vWF from blood group O plasma.
      Within the GalNAc-recognizing lectins examined, a biantennary complex-type
      oligosaccharide having the blood group A structure retarded on an HPA-agarose
      column, and the affinity was diminished after digestion with alpha-N
      acetylgalactosaminidase. This product bound to UEA-I agarose column. These
      results indicate that HPA and UEA-I are most sensitive for detection of
      glycoproteins possessing small amounts of blood group A and H antigens and also
      useful for fractionation of complex-type oligosaccharides with blood group A and
      H antigens, respectively.

PMID- 11342254
TI  - Characterization of blood group ABO(H)-active gangliosides in type AB
      erythrocytes and structural analysis of type A-active ganglioside variants in
      type A human erythrocytes.
AB  - Several monosialogangliosides containing the type A-active epitope have been
      detected in type A erythrocytes on immunological analysis with a monoclonal
      antibody, and three of them were purified by repeated silica bead column
      chromatography and by scraping from the TLC plate. Two of these A-active
      gangliosides were characterized by methylation analysis by GC/MS, negative SIMS,
      MALDI-TOF/MS, proton nuclear magnetic resonance spectroscopy, and immunological
      assays, and their structures were concluded to be as follows. A-active
      ganglioside I:A-active ganglioside II:The reactivity of the purified gangliosides
      to the anti-A monoclonal antibodies (mAbs) exhibited enhancement after removal of
      the sialic acid. Therefore, the sialic residue has been shown to inhibit the
      binding to the terminal A-active epitope through the formation of an immune
      complex. To confirm the presence of A- (including S-A-I, -II and -III) and B
      active gangliosides, the reactivity of anti-A and -B mAbs were investigated using
      total gangliosides from type A, -B and -AB erythrocytes on TLC plate. The results
      were that the gangliosides from types A and AB showed positive reaction to anti-A
      mAbs, whereas in the anti-B mAbs binding the gangliosides from types B and AB
      were positive. Thus, it revealed that A-active gangliosides were present in type
      A and -AB, and B-active gangliosides in types B and AB. As there was no
      difference in respective gangliosides on type AB erythrocytes of 22 individuals,
      both A- and B-active gangliosides are equally present in type AB erythrocytes.
      The biological significance of these A- and B-active ganglioside variants remains
      vague at present. As these molecules exhibit different reactivities to the anti-A
      mAbs, it is very likely that they can regulate the antigenicity of the A-epitope
      on the cell surface.

PMID- 11342255
TI  - Cellular sites of H2O2-induced damage and their protection by nitroxides.
AB  - While the exact mechanism of H2O2-induced cytotoxicity is unknown, there is
      considerable evidence implicating DNA as a primary target. A recent study showed
      that a cell-impermeable nitroxide protected mammalian cells from H2O2-induced
      cell killing and suggested that the protection was mediated through cell membrane
      bound or extracellular factors. To further define the protective properties of
      nitroxides, Chinese hamster V79 cells were exposed to H2O2 with or without cell
      permeable and impermeable nitroxides and selected metal chelators. EPR
      spectroscopy and paramagnetic line broadening agents were used to distinguish
      between intra- and extracellular nitroxide distribution. To study the
      effectiveness of nitroxide protection, in the absence of a cell membrane, H2O2
      mediated damage to supercoiled plasmid DNA was evaluated. Both deferrioxamine and
      Tempol cross the cell membrane, and inhibited H2O2-mediated cell killing, whereas
      the cell-impermeable DTPA and nitroxide, CAT-1, failed to protect. Similar
      protective effects of the chelators and nitroxides were observed when L
      histidine, which enhances intracellular injury, was added to H2O2. In contrast,
      when damage to plasmid DNA was induced (in the absence of a cell membrane), both
      nitroxides were protective. Collectively, these results do not support a role for
      membrane-bound or extracellular factors in mediating H2O2 cytotoxicity in
      mammalian cells.

PMID- 11342256
TI  - Cinnamophilin as a novel antiperoxidative cytoprotectant and free radical
      scavenger.
AB  - The antioxidant properties of cinnamophilin were evaluated by studying its
      ability to react with relevant reactive oxygen species, and its protective effect
      on cultured cells and biomacromolecules under oxidative stress. Cinnamophilin
      concentration-dependently suppressed non-enzymatic iron-induced lipid
      peroxidation in rat brain homogenates with an IC50 value of 8.0+/-0.7 microM and
      iron ion/ADP/ascorbate-initiated rat liver mitochondrial lipid peroxidation with
      an IC50 value of 17.7+/-0.2 microM. It also exerted an inhibitory activity on
      NADPH-dependent microsomal lipid peroxidation with an IC50 value of 3.4+/-0.1
      microM without affecting microsomal electron transport of NADPH-cytochrome P-450
      reductase. Both 1,1-diphenyl-2-picrylhydrazyl and 2,2'-azo-bis(2-amidinopropane)
      dihydrochloride-derived peroxyl radical tests demonstrated that cinnamophilin
      possessed marked free radical scavenging capacity. Cinnamophilin significantly
      protected cultured rat aortic smooth muscle cells (A7r5) against alloxan/iron
      ion/H2O2-induced damage resulting in cytoplasmic membranous disturbance and
      mitochondrial potential decay. By the way, cinnamophilin inhibited copper
      catalyzed oxidation of human low-density lipoprotein, as measured by fluorescence
      intensity and thiobarbituric acid-reactive substance formation in a concentration
      dependent manner. On the other hand, it was reactive toward superoxide anions
      generated by the xanthine/xanthine oxidase system and the aortic segment from
      aged spontaneously hypertensive rat. Furthermore, cinnamophilin exerted a
      divergent effect on the respiratory burst of human neutrophil by different
      stimulators. Our results show that cinnamophilin acts as a novel antioxidant and
      cytoprotectant against oxidative damage.

PMID- 11342257
TI  - Studies on reactions of oxidizing sulfur-sulfur three-electron-bond complexes and
      reducing alpha-amino radicals derived from OH reaction with methionine in aqueous
      solution.
AB  - The technique of pulse radiolysis with spectrophotometric detection has been used
      to investigate the possibility of electron transfer reactions between oxidizing
      sulfur-sulfur three-electron-bond complexes (Met2/S thereforeS+), or reducing
      alpha-amino radicals (CH3SCH2CH2CH.NH2) derived from reaction of methionine with
      OH radicals and hydroxycinnamic acid (HCA) derivatives, riboflavin (RF) or flavin
      adenine dinucleotide (FAD), respectively. The HCA derivatives, such as caffeic
      acid, ferulic acid, sinapic acid and chlorogenic acid, widely distributed
      phenolic acids in fruit and vegetables, have been identified as good antioxidants
      previously can rapidly and efficiently repair oxidizing three-electron-bond
      complexes via electron transfer. RF and FAD can oxidize reducing alpha-amino
      radicals derived from methionine. The electron transfer rate constants
      approximately 10(9) dm3 x mol(-1)x s(-1) were determined by following the build
      up kinetics of species produced.

PMID- 11342258
TI  - Changes in hydration, protein and proteoglycan composition of the collagen
      keratocyte matrix of the bovine corneal stroma ex vivo in a bicarbonate-mixed
      salts solution, compared to other solutions.
AB  - Many solutions have been used to investigate the swelling properties of the
      mammalian corneal stroma but few of the solutions resemble the expected
      extracellular matrix fluid of the corneal stroma, and little information is
      available on whether incubation ex vivo causes significant changes in the gross
      composition of the stroma. From quality-selected recent post-mortem eyes of adult
      cattle, stroma preparations were cut from the central part of the cornea. The
      time-dependent changes in wet mass were assessed over 9 h at 37 degrees C, and
      the preparations then dried. Various solutions of known pH (6.88-8.32) and
      osmolality (<50-327 mosmol/kg) were used, and were assayed for protein and
      proteoglycan after the incubation. The rates and extent of stromal swelling were
      lowest in a glucose-supplemented mixed salts solution containing 35 mM
      bicarbonate (0.5% CO2) solution, marginally greater in a mixed salts solution
      containing 35 mM bicarbonate (5% CO2) or similar non-bicarbonate mixed salts
      solutions (including BSS), and progressively greater in phosphate-buffered saline
      (PBS), various phosphate buffers (10-67 mM) and saline solutions (0.025-1%), and
      greatest in water. The initial rates of swelling ranged from 44 to 451 mg/h and
      the secondary rates from 9 to 106 mg/h. In all solutions, protein and
      proteoglycans were detected, but these ranged from around 1 to 10% of the samples
      with the bicarbonate-buffered solutions, to around 30% with the use of some
      phosphate buffers or saline.

PMID- 11342259
TI  - Reaction rates of oxygen with hemoglobin measured by non-equilibrium facilitated
      oxygen diffusion through hemoglobin solutions.
AB  - The purpose of this study was to verify the concept of non-equilibrium
      facilitated oxygen diffusion. This work succeeds our previous study, where
      facilitated oxygen diffusion by hemoglobin was measured at conditions of chemical
      equilibrium, and which yielded diffusion coefficients of hemoglobin and of
      oxygen. In the present work chemical non-equilibrium was induced using very thin
      diffusion layers. As a result, facilitation was decreased as predicted by theory.
      Thus, this work presents the first experimental demonstration of non-equilibrium
      facilitated oxygen diffusion. In addition, association and dissociation rate
      parameters of the reaction between oxygen and bovine and human hemoglobin were
      calculated and the effect of the homotropic and heterotropic interactions on each
      rate parameter was demonstrated. The results indicate that the homotropic
      interaction--which leads to increasing oxygen affinity with increasing
      oxygenation--is predominantly due to an increase in the association rate. The
      heterotropic interaction--which leads to decreasing oxygen affinity by anionic
      ligands--appears to be effected in two ways. Cl- increases the dissociation rate.
      In contrast, 2,3-diphosphoglycerate decreases the association rate.

PMID- 11342260
TI  - Insulin-like growth factor-I stimulates amino acid transport in a glutamine
      deprived human neuroblastoma cell line.
AB  - It is still unknown how insulin-like growth factor-I (IGF-I) regulates cancer
      cell growth in the condition of the limited availability of key nutrients, such
      as glutamine. We investigated the effects of IGF-I on cell growth and amino acid
      transport in a glutamine-deprived human neuroblastoma cell line, SK-N-SH. Cell
      growth was measured, and 3H-labeled amino acid transport was assayed after
      treatment with or without IGF-I (50 ng/ml) in 2 mM (control) and 100 microM
      glutamine concentrations. Cell growth rates were dependent on glutamine
      concentrations. IGF-I stimulated cell growth in both 2 mM and 100 microM
      glutamine. IGF-I stimulated glutamine transport in 100 microM glutamine with the
      mechanism of increasing carrier Vmax, but had no effect in 2 mM glutamine. IGF-I
      also stimulated leucine, glutamate and 2-(methylamino)isobutyric acid transport
      in 100 microM glutamine. There were significant increases in [3H]thymidine and
      [3H]leucine incorporation in IGF-I-treated cells in both 2 mM and 100 microM
      glutamine. These data suggest that IGF-I stimulates cell growth by increasing
      amino acid transport in the condition of low glutamine levels in a human
      neuroblastoma cell line. This mechanism may allow to maintain cell growth even in
      nutrient-deprived tumor tissues.

PMID- 11342261
TI  - Effect of bile acids on the uptake of irinotecan and its active metabolite, SN
      38, by intestinal cells.
AB  - The intestinal transport of irinotecan (CPT-11) and its active metabolite, SN-38,
      has been previously reported (K. Kobayashi et al., Int. J. Cancer, 83 (1999) 491
      496). In the present study, the effect of the two major primary bile acids,
      cholic acid (CA) and taurocholic acid (TCA), on the uptake of CPT-11 and SN-38 by
      hamster intestinal epithelial cells was investigated. These two bile acids at
      concentrations up to 200 microM did not directly alter the cellular uptake of CPT
      11 and SN-38. However, under physiologically acidic intestinal pH conditions,
      micelle formation induced by 20 mM TCA significantly reduced the cellular uptake
      of CPT-11 and SN-38 by 60% and 80%, respectively.

PMID- 11342262
TI  - A possible solvent effect of adenosine diphosphate influences the binding of 1,N6
      ethenoadenosine diphosphate to myosin from skeletal muscle.
AB  - Skeletal muscle myosin displays two independent and equivalent binding sites for
      1,N6 ethenoadenosine diphosphate, with a dissociation constant of 24.7 microM.
      MgADP, 10 to 40 microM, behaves as a pure competitive type inhibitor (K(SI)=8-9
      microM) for the binding of 1,N6 ethenoadenosine diphosphate to skeletal muscle
      myosin. On the contrary, the inhibition by MgADP, 0.11-1.54 mM, is neither
      competitive nor non-competitive nor mixed, as is revealed by the analysis with
      the general kinetic equation (K.J. Laidler, P.S. Bunting, The Chemical Kinetics
      of Enzyme Action, 2nd ed., Clarendon, Oxford, 1973, p. 94). To explain our
      finding we propose that MgADP operates a complex type of inhibition, acting both
      directly as a competitor for myosin active sites, and indirectly by perturbing
      the regions of the solvent near to the protein.

PMID- 11342263
TI  - Oxidative changes in brain pyridine nucleotides and neuroprotection using
      nicotinamide.
AB  - Pyridine nucleotides are critical during oxidative stress due to their roles in
      reductive reactions and energetics. The aim of the present study was to examine
      pyridine nucleotide changes in six brain regions of mice after an
      intracerebroventricular injection of the oxidative stress inducing agent, t-butyl
      hydroperoxide (t-BuOOH). A secondary aim was to investigate the correlation
      between NAD+ levels and DNA fragmentation. Here, we demonstrate that t-BuOOH
      induced a rapid oxidation of NADPH and a slow depletion of NAD+ in most brain
      regions. A slight increase in NADH also occurred in five brain regions. NAD+
      depletion was associated with increased DNA fragmentation. This suggests the
      initiation of a death cascade involving poly(ADP-ribose) polymerase (PARP), NAD+,
      ATP depletion and consequent cell death in brain tissue. PARP activity was
      accelerated in some brain regions after 20 min of oxidative stress. To counteract
      oxidative stress induced toxicity, NAD+ levels were increased in the brain using
      an intraperitoneal injection of nicotinamide. A surplus of brain NAD+ prevented
      DNA fragmentation in some brain regions. Nicotinamide administration also
      resulted in higher brain NADH, NADP+ and NADPH levels in some regions. Their
      synthesis was further upregulated during oxidative stress. Nicotinamide as a
      precursor for NAD+ may provide a useful therapeutic strategy in the treatment of
      neurodegeneration.

PMID- 11342264
TI  - Structural characteristics of the N-glycans of two isoforms of prostate-specific
      antigens purified from human seminal fluid.
AB  - Prostate-specific antigen (PSA) is a glycosylated chymotrypsin-like serine
      protease and is found mainly in prostatic tissue and seminal fluid. We purified
      two forms of PSA (PSA-A and PSA-B) from human seminal fluid with pI values of
      approx. 7.2 and approx. 6.9, respectively. To characterize the N-glycans of the
      two isoforms, the sugar chains were liberated by hydrazinolysis followed by N
      acetylation, and derivatized with 2-aminobenzamide. Both PSA-A and PSA-B
      contained mono- and disialylated sugar chains, although PSA-B had a much higher
      content of the latter. After removal of sialic acid residues by sialidase
      digestion, mono- and biantennary N-glycans and three outer chain moieties
      (Galbeta1-4GlcNAcbeta1-, GlcNAcbeta1-, GalNAcbeta1-4GlcNAcbeta1-) were found in
      both samples. However, the ratios of each N-glycan were different. These results
      indicate that PSA-A and PSA-B differ not only in their sialic acid contents, but
      also in their outer chain features.

PMID- 11342265
TI  - Molecular association of betaine and betaine hydrochloride in aqueous solutions-
      a study by Raman spectroscopy.
AB  - Raman vibrational spectroscopy, at 298 K, has been used to study the hydration of
      betaine hydrochloride and betaine in the concentration range 0.5-2 M. The
      observed changes in the internal vibrations of the solutes, namely, in the C=O,
      COO- and C-H stretchings, and in the components of the O-H stretching band are
      consonant with anionic water-betaine and betaine hydrochloride dimeric species
      involving simultaneously hydrogen-bonding between two solute and water molecules.
      In both cases, betaine hydrochloride and 'zwitterionic' betaine behave like
      structure-makers promoting a larger association in the 'bulk' liquid water.

PMID- 11342266
TI  - Pathophysiological significance of in vivo ESR signal decay in brain damage
      caused by X-irradiation. Radiation effect on nitroxyl decay of a lipophilic spin
      probe in the head region.
AB  - X-irradiation of mice decreased the decay rate of the in vivo ESR signal in the
      head region to 75% of the control when 3-methoxycarbonyl-2,2,5,5
      tetramethylpyrrolidine-1-yloxy (MCPROXYL), a lipophilic and blood-brain barrier
      permeable spin probe, was used. We attempted to identify the specific factor
      responsible for the decrease in the signal decay rate caused by X-irradiation.
      The signal decay of MCPROXYL in the head region depends on the following three
      factors: (1) blood concentration of MCPROXYL, (2) reduction to the corresponding
      hydroxylamine in the brain tissue, and (3) effusion of MCPROXYL from the brain
      tissue. Irradiation at 15 Gy did not significantly change the rate of decrease of
      blood concentration of MCPROXYL at 1 h post-irradiation. The reducing activity of
      the brain homogenate was not changed by the X-irradiation (15 Gy). The contents
      of MCPROXYL and its hydroxylamine derivative in the brain of 15 Gy-irradiated
      mice remained higher than in non-irradiated mice. These findings suggest that the
      effect of X-irradiation observed by in vivo ESR is attributable not to the redox
      reaction of MCPROXYL in the brain but to the change of the efflux rate of the
      MCPROXYL from the brain.

PMID- 11342267
TI  - Reduction of dehydroascorbic acid by homocysteine.
AB  - To determine the reductive process of extracellular dehydroascorbic acid (DHA),
      molecules (homocysteine, homocysteine thiolactone, methionine, cysteine, and
      homoserine) were tested to identify those with the potential to reduce DHA to
      ascorbic acid (AA). Homocysteine (Hcy) was the most potent of the molecules
      tested. The efficacy of Hcy was compared with that of other molecules able to
      reduce DHA (reduced glutathione (GSH) and cysteine (Cy)). Although all three
      molecules were able to reduce DHA, GSH and Cy were not to reduce DHA to AA at
      concentrations lower than 100 micromol/l, and only less than 5% DHA was reduced
      to AA at concentrations of 200-300 micromol/l. In contrast, Hcy reduced DHA to AA
      stoichiometrically at concentrations as low as 10 micromol/l. In Jurkat and U937
      cells, the increasing concentrations of extracellular Hcy suppressed
      intracellular dehydroascorbic acid uptake, indicating that extracellular
      reduction of DHA by Hcy leads to decreasing extracellular DHA available for its
      intracellular uptake. Simultaneous oxidation and reduction of Hcy and DHA were
      accelerated extracellularly in the presence of quercetin, an inhibitor of DHA
      uptake, suggesting that extracellular ascorbic acid concentration increased via
      blocking DHA uptake by quercetin and reducing extracellular DHA by Hcy. The
      effect of homocysteine on DHA reduction and uptake was confirmed with human
      umbilical vein endothelial cells. The oxidation of Hcy also prevented the
      decrease in DNA synthesis in human umbilical vein endothelial cells, which would
      occur following exposure to Hcy.

PMID- 11342268
TI  - Development of proteo-chemometrics: a novel technology for the analysis of drug
      receptor interactions.
AB  - A novel method for the analysis of drug receptor interactions has been developed
      and used to explore mechanisms involved in the binding of 4-piperidyl oxazole
      antagonists to alpha1a-, alpha1b- and alpha1d-adrenoceptors. The method exploits
      affinity data for a series of organic chemical compounds binding to wild-type and
      artificially mutated receptors. The receptor sequences and compounds are assigned
      predictor variables that are correlated to the measured pharmacological
      activities using partial least-squares projections to latent structures. The
      predictor variables consist of one descriptor block derived from the chemical
      properties of the receptors' primary amino acid sequences and another descriptor
      block derived from the chemical properties of the organic compounds. The cross
      terms generated from the two descriptor blocks are also derived. Using this
      approach, very sturdy models were generated describing the interactions of the
      chemical compounds with the receptors. Models are useful to predict binding
      affinity and receptor subtype selectivity of compounds prior to their synthesis,
      and may find use in rational drug design. Moreover, models also give quantitative
      information about the interactions of the amino acids of the receptors with the
      ligands, thereby giving an insight into the molecular mechanisms involved in
      ligand binding.

PMID- 11342269
TI  - Construction of tumor-specific cells expressing a membrane-anchored single-chain
      Fv of anti-ErbB-2 antibody.
AB  - Cells expressing a membrane-anchored single-chain fragment variable (scFv) domain
      against a tumor-specific antibody were fabricated. These cells were able to bind
      to cells of a human colon cancer line (BM314) expressing the erbB-2 proto
      oncogene. A plasmid, pMFverbB, was first constructed in which the anti-ErbB-2
      scFv gene was cloned in-frame between a signal peptide sequence and the platelet
      derived growth factor receptor (PDGFR) transmembrane domain gene to express scFv
      on the cell surface. An African green monkey cell line, COS-1, was stably
      transfected with pMFverbB. Immunofluorescence assay experiments and microscopic
      observation showed that the cells expressing scFv bound to the human tumor cells
      overexpressing the ErbB-2 protein as well as to cells of a mouse fibroblast line
      (NIH-3T3) transfected with the erbB-2 gene. The cells expressing scFv could take
      up magnetite cationic liposomes as a model of particle-type drug and retained the
      ability to target ErbB-2-expressing cells. The fabricated cells have the
      potential to serve as drug carriers in drug targeting applications.

PMID- 11342277
TI  - Slow detection reaction can mimic initial inhibition of an enzymic reaction.
AB  - An analysis of sigmoid-shaped progress curves in the reaction between Electric
      Eel acetylcholinesterase (acetylcholine acetylhydrolase, EC 3.1.1.7, AChE) and
      its substrate acetylthiocholine in low concentrations at pH 7 is presented. In
      order to be able to explain an initial apparent inhibition of the enzyme
      substrate reaction, the rate of detection reaction had to be taken into account.
      The theoretical curves obtained by the fitting of differential equations for the
      reaction mechanism to the data of six progress curves simultaneously, exactly
      reproduce the course of the experimental curves. The measurements performed with
      various concentrations of detection reagent confirm the proposed cause of
      sigmoidity.

PMID- 11342278
TI  - Synthesis and in-vitro evaluation of novel low molecular weight thiocarbamates as
      inhibitors of human leukocyte elastase.
AB  - A series of novel low molecular weight thiocarbamate esters (1e-6e) were
      synthesized and evaluated as inhibitors of human leukocyte elastase (HLE). The
      thiocarbamate esters studied consist of a substituted primary or secondary
      aliphatic or aromatic amine and a 1-phenyl-1H-tetrazole-5-thiol (Table I). The
      HLE catalyzed hydrolysis of N-methoxysuccinyl- L-Ala-L-Ala-L-Pro-L-Val-p
      nitroanilide substrate was utilized as the measure of inhibition. N-n-butyl, 1
      phenyl-1H-tetrazole-5-thiocarbamate (1e) exhibited the highest inhibitory
      activity (k(obs) /[I] = 2.1 x 10(5) M(-1). min(-1) ) and N-allyl, 1-phenyl-1H
      tetrazole-5-thiocarbamate (2e) (K(obs) /[I] = 6.1 x 10(4) M(-1). min(-1) )
      exhibited the second highest inhibitory activity of all the thiocarbamates. The
      aromatic N-phenyl, 1-phenyl-1H-tetrazole-5-thiocarbamate (4e) showed the lowest
      inhibitory activity (K(obs) /[I] = 1.9 x 10(2) M(-1). min(-1) ) among the N
      monosubstituted derivatives, similar to that of N-ethyl-N-n-butyl, 1-phenyl-1H
      tetrazole-5-thiocarbamate (5e) (K(obs) /[I] = 1.8 x 10(2) M(-1).min(-1) ). The N
      isopropyl, 1-phenyl-1H-tetrazole-5-thiocarbamate (3e) (K(obs) /[I] = 3.3 x 10(3)
      M(-1).min(-1) ) was about 10 fold more active than (4e) and N, N-diisopropyl, 1
      phenyl-1H-tetrazole- 5-thiocarbamate (6e) showed no inhibitory activity against
      HLE. In the present work less than 3% of HLE specific activity was regained after
      24 hours incubation with each of the tested N-monosubstituted thiocarbamates (1e
      4e). The time-dependent inhibition of HLE by the thiocarbamate compounds (1e-5e)
      seems to involve the interaction and possible chemical modification of one enzyme
      residue. Straight chain nonpolar aliphatic substituents on the nitrogen of the
      thiocarbamate functionality may be essential for high inhibitory activity. As the
      degree of substitution (branching) on the nitrogen of the thiocarbamate
      functionality increases the inhibitory activity of the compounds decreases. The
      time-dependent inhibition of HLE and the slow deacylation rates by the N
      monosubstituted thiocarbamates are consistent with irreversible inhibition.

PMID- 11342279
TI  - Inhibition of chitin synthetase from Saccharomyces cerevisiae by a new UDP-GlcNAc
      analogue.
AB  - The synthesis and biological evaluation of a new UDP-GlcNAc competitor (I),
      designed to mimic the transition state of the sugar donor in the enzymatic
      reaction catalysed by chitin synthetase, is described. Compound (I) was found to
      competitively inhibit chitin synthetase from Saccharomyces cerevisiae with
      respect to UDP-GlcNAc, but displayed minimal antifungal activity.

PMID- 11342280
TI  - Carbonic anhydrase inhibitors: synthesis and inhibition against isozymes I, II
      and IV of topically acting antiglaucoma sulfonamides incorporating cis-5
      norbornene-endo-3-carboxy-2-carboxamido moieties.
AB  - Sulfonamides incorporating cis-5-norbornene-endo-3-carboxy-2-carboxamido moieties
      in their molecules were prepared by reaction of cis-5-norbornene-endo-2,3
      dicarboxylic anhydride with aromatic/heterocyclic sulfonamides possessing free
      amino, hydrazino, or imino groups. Some of these compounds showed very good CA II
      and CA IV inhibitory properties, with affinities for the enzymes in the low
      nanomolar range. Some of the most active CA II inhibitors reported here have been
      formulated as aqueous solutions for topical administration as antiglaucoma agents
      in normotensive rabbits. Some of the derivatives incorporating cis-5-norbornene
      endo-3-carboxy-2-carboxamido and aromatic sulfonamide moieties (as sodium salts)
      showed effective and longer lasting intraocular pressure (IOP) lowering as
      compared to dorzolamide, a widely used topical antiglaucoma drug. Compounds
      incorporating cis-5-norbornene-endo-2,3-carboximido moieties, although stronger
      in vitro CA inhibitors as compared to the corresponding cis-5-norbornene-endo-3
      carboxy-2-carboxamido-;derivatives, showed no topical IOP lowering properties,
      probably due to their very poor water solubility.

PMID- 11342281
TI  - Carbonic anhydrase inhibitors, interaction of boron derivatives with isozymes I
      and II: a new binding site for hydrophobic inhibitors at the entrance of the
      active site as shown by docking studies.
AB  - The interaction of human carbonic anhydrase (hCA) isozymes I and II with boron
      derivatives was investigated by kinetic and spectroscopic studies. These
      derivatives, tested as new inhibitors of carbonic anhydrase, are sulfonamide and
      non-sulfonamide boron derivatives and some of them proved to be moderately
      efficient inhibitors of hCA I and hCA II, their activities being comparable to
      those of the unsubstituted sulfonamides, the classical inhibitors of these zinc
      enzymes. Ph(2) BOH, one of the compounds with the highest affinity for hCA II in
      the present study, has been docked within the active site. After minimisation it
      was found situated at 7.9 A from zinc, within the hydrophobic half of the active
      site, in Van der Waals contacts with the amino acid residues: Val 121, Phe 130,
      Val 135, Leu 141, Val 143, Val 207 and Pro 201. This is the first time that a CA
      inhibitor has been found to bind at the edge of the active site cavity, similarly
      to the CA activator histamine, which binds on the hydrophilic half. This finding
      may be of importance also for the design of novel types of inhibitors with
      increased affinity for the different CA isozymes.

PMID- 11342282
TI  - Inhibition of potato polyphenol oxidase by anions and activity in various
      carboxylate buffers (pH 4.8) at constant ionic strength.
AB  - The activity of potato polyphenol oxidase (tyrosinase) toward DL-3,4
      dihydroxyphenylalanine (K(M) 5.39 mM) was studied using a variety of carboxylate
      buffers at a common pH and ionic strength. Enzyme activity, greatest in citrate
      and least in oxalate, correlated with increasing carboxyl concentration and
      molecular mass. The lower activity in oxalate was attributed to more effective
      chelation of a copper(II) form of the enzyme by the oxalate dianion. Sodium
      halide salts inhibited the enzyme. Although there was little difference in
      inhibition between sodium and potassium salts, the degree and type of inhibition
      was anion dependent; K(is), values for NaCl and KCl, (competitive inhibitors)
      were 1.82 and 1.62 mM, whereas Na(2) SO(4) and K(2) SO(4) (mixed inhibitors) had
      K(is) and K(ii) values in the 250 to 450 mM range.

PMID- 11342283
TI  - Inhibition of pig liver and Zea mays L. polyamine oxidase: a comparative study.
AB  - Polyamine oxidase (PAO) is involved in polyamine metabolism and production of
      hydrogen peroxide in animal and plants, thus representing a key system in
      development and programmed cell death. In the present study, the inhibitory
      effect of amiloride, p-aminobenzamidine, clonidine, 4',6-diamidino-2-phenyl
      indole (DAPI), gabexate mesylate, guazatine, and N,N'-bis(2,3-butadienyl)-1,4
      butane-diamine (MDL72527) on the catalytic activity of pig liver and Zea mays L.
      PAO, Lens culinaris L. and Pisum sativum L. and swine kidney copper amine
      oxidase, bovine trypsin, as well as neuronal constitutive nitric oxide synthase
      (NOS-I) was investigated. Moreover, agmatine and N(3) -prenylagmatine (G3) were
      observed to inhibit pig liver and Zea mays L. PAO, bovine trypsin, and NOS-I
      action, but were substrates for Lens culinaris L., Pisum sativum L. and swine
      kidney copper amine oxidase. Guazatine and G3 inhibited selectively Zea mays L.
      PAO with K(i) values of 7.5 x 10(-9) M and 1.5 x 10(-8) M, respectively (at pH
      6.5 and 25.0 degrees C). As a whole, the data reported here represent examples of
      enzyme cross-inhibition, and appear to be relevant in view of the use of cationic
      L-arginine-and imidazole-based compounds as drugs.

PMID- 11342284
TI  - Evidence for an essential arginine in the flavoprotein nitroalkane oxidase.
AB  - The flavoprotein nitroalkane oxidase from the fungus Fusarium oxysporum catalyzes
      the oxidative denitrification of primary or secondary nitroalkanes to yield the
      respective aldehydes or ketones, hydrogen peroxide and nitrite. The enzyme is
      inactivated in a time-dependent fashion upon treatment with the arginine-directed
      reagents phenylglyoxal, 2,3-butanedione, and cyclohexanedione. The inactivation
      shows first order kinetics with all reagents. Valerate, a competitive inhibitor
      of the enzyme, fully protects the enzyme from inactivation, indicating that
      modification is active site directed. The most rapid inactivation is seen with
      phenylglyoxal, with a k(inact) of 14.3 +/- 1.1 M(-1) min(-1) in phosphate buffer
      at pH 7.3 and 30 degrees C. The lack of increase in the enzymatic activity of the
      phenylglyoxal-inactivated enzyme after removing the unreacted reagent by gel
      filtration is consistent with inactivation being due to covalent modification of
      the enzyme. A possible role for an active site arginine in substrate binding is
      discussed.

PMID- 11342285
TI  - Purification and characterization of catalase from chard (Beta vulgaris var.
      cicla).
AB  - Catalase is a major primary antioxidant defence component that primarily
      catalyses the decomposition of H(2) O(2) to H(2) O. Here we report the
      purification and characterization of catalase from chard (Beta vulgaris var.
      cicla). Following a procedure that involved chloroform treatment, ammonium
      sulfate precipitation and three chromatographic steps (CM-cellulose, Sephadex G
      25, and Sephadex G-200), catalase was purified about 250-fold to a final specific
      activity of 56947 U/mg of protein. The molecular weight of the purified catalase
      and its subunit were determined to be 235 000 and 58 500 daltons, indicating that
      the chard catalase is a tetramer. The absorption spectra showed a soret peak at
      406 nm, and there was slightly reduction by dithionite. The ratio of absorption
      at 406 and 275 nanometers was 1.5, the value being similar to that obtained for
      catalase from other plant sources. In the catalytic reaction, the apparent Km
      value for chard catalase was 50 mM. The purified protein has a broad pH optimum
      for catalase activity between 6.0 and 8.0. The enzyme had an optimum reaction
      temperature at 30 degrees C. Heme catalase inhibitors, such as azide and cyanide,
      inhibited the enzyme activity markedly and the enzyme was also inactivated by ?
      mercaptoethanol, dithiothreitol and iodoacetamide.

PMID- 11342286
TI  - Evaluation of theophylline-stimulated changes in carnitine palmitoyltransferase
      activity in skeletal muscle and liver of rats.
AB  - The effect of theophylline treatments on the activity of carnitine
      palmitoyltransferase (CPT) in skeletal muscle and the liver of rats was
      investigated. Theophylline was administered at 100 mg/kg bw/day and effects were
      monitored after a treatment period that lasted between a week and five weeks.
      Results showed that a significant increase in the activity of CPT was observed in
      skeletal muscle of theophylline-treated groups as compared to either control or
      placebo groups. However, there was no significant change in the activity of CPT
      in the hepatic tissues of theophylline-treated groups. The observed discrepancies
      in activity of CPT might be due to the presence of two isoenzymes, the muscle
      type (M-CPT) and liver type (L-CPT); it is possible that theophylline affects
      only M-CPT activity.

PMID- 11342287
TI  - Study of diastereomeric thioureas formed with a new chiral derivatizing agent.
AB  - (1S,2S)-1,3-Diacetoxy-1-(4-nitrophenyl)-2-propyl isothiocyanate ((S,S)-DANI) was
      recently introduced as a new chiral derivatizing agent for the enantioseparation
      of amino compounds. In the present study, diastereomeric derivatives of racemic
      amino acids were formed with (S,S)-DANI. The thioureas produced were
      distinguished by means of infrared spectroscopy, theoretical calculations and
      high-performance liquid chromatography. The differences observed between the
      corresponding diastereomers by the independent methods are considered to prove
      the applicability of the new reagent in the field of enantiomer separation.

PMID- 11342288
TI  - Determination of the absolute configuration of synthetic pterocarpans by chiral
      HPLC using on-line CD detection.
AB  - Resolution of synthetic racemic pterocarpans was achieved by CD monitored HPLC
      using a chiral stationary phase. No sign of exciton coupling was seen in the CD
      spectra of the pterocarpan enantiomers. The predominance of the chromane
      chromophore was indicated by the high intensity of the (1) L(b) band. The
      chirality of both the chromane and dihydrobenzo[b]furane chromophores was found
      to be governed by the second chiral sphere. An oxygen atom in pseudoaxial
      position at the benzylic atom of the chroman ring system gave rise to an
      increased third-sphere contribution and the positive sign of the (1) L(b) and
      negative sign of the (1) L(a) band. This resulted in a general positive-negative
      negative sign pattern of the (1) L(b), (1) L(a) and (1) B(b) bands of the second
      eluted enantiomer of P helicity suggesting homochirality and the same absolute
      configuration of the chiral centers.

PMID- 11342289
TI  - Chirality and art-ropes and twisted strings in paintings.

PMID- 11342290
TI  - Diastereoselection through chiral conformations.
AB  - Chiral conformations of flexible molecules may develop in a concerted manner if
      the molecule is crowded enough to assure sufficient level of through-the-space
      contacts. Higher number (> 4) of groups connected to the same atom, as in many
      coordination compounds, can be advantageous in this respect. The case study of
      R,S-[(sec-butoxycarbonyl)methyl]cobalt tricarbonyl triphenylphosphine is
      presented here. X-ray diffraction shows that the possible number of enantiomeric
      and diastereomeric conformations is reduced by 75% (from 8 to 2) by concerted
      development of the molecular conformations in crystalline phase.

PMID- 11342291
TI  - Semipreparative scale enantioseparation of racemic amine and amino ester hydrogen
      perchlorate salts using a silica gel-bound optically active di-tert-butylpyridino
      18-crown-6 ligand.
AB  - We report herein results on the enantioseparation of selected racemic amine and
      amino ester hydrogen perchlorate salts using a silica gel-bound optically pure
      chiral di-tert-butylpyridino-18-crown-6 ligand (R,R)-1. The effect of solvent
      composition was studied using appropriate binary and ternary solvent mixtures as
      eluents. We found that acetonitrile/ methanol/ dichloromethane (MeCN/MeOH/CH2 Cl2
      ) ternary solvent mixtures gave better enantioseparations for the racemic salts
      using chiral stationary phase (R,R)-1 than any of the binary ones. In the present
      paper we also describe the studies of chromatographic parameters such as loading,
      flow rate and eluent polarity.

PMID- 11342292
TI  - The interaction of R(+)- or S(-)-2,2'-diamino-1,1'-binaphthalene with a Pd/silica
      catalyst in tetrahydrofuran.
AB  - The interaction of 2,2'-diamino-1,1'-binaphthalene over a Pd/silica catalyst and
      its interaction with hydrogen in the system and with the solvent tetrahydrofuran,
      (THF) has been investigated. Three interactions have been identified, i)
      conversion of amine groups to hydroxy groups, ii) hydrogenation of one or more of
      the aromatic rings, and iii) reaction between the amine group(s) and the THF
      solvent.

PMID- 11342293
TI  - One-wedge convention for stereochemical representations.
AB  - We propose that various bonds (see figure below) used for specification of
      absolute configuration, e.g. the two types (I and II) of solid wedge and broken
      wedge representation most frequently seen in literature, can be replaced by only
      one kind of wedge, namely the solid wedge (III and IV). Only one wedge should be
      used when representing a quadrivalent center (IV). The three normal bonds are
      distributed on a cone opposite to the wedge. The flexibility, simplicity,
      unambiguity and usefulness for R-S specification of the one-wedge system are
      discussed, as well as its esthetic appeal.

PMID- 11342294
TI  - Asymmetric synthesis of biologically useful 3,4-disubstitutedgamma- lactone (3,4
      db).
AB  - 3,4-Disubstituted gamma-lactones 9 and 10 were stereoselectively synthesized from
      3,4-unsaturated aliphatic alcohol. The synthetic methods of homoallylic alcohol
      were discussed. Asymmetric dihydroxylation of the double bond was performed by
      Sharpless' method with (DHQD)2 PHAL or (DHQ)2 PHAL. The stereochemistry of the
      product was assigned. The (3R,4R)- and (3S,4S)-compounds were obtained with high
      enantiomeric excess.

PMID- 11342295
TI  - Stepwise lineage restriction of progenitors in lympho-myelopoiesis.
AB  - It has long been controversial whether hematopoiesis progresses through ordered
      stages of determination as in embryonic development. This is due to the absence
      of a methodology capable of exactly determining the developmental potential of
      hematopoietic stem/progenitor cells. The multilineage progenitor (MLP) assay
      enabled us to discriminate among seven types of hematopoietic progenitors, which
      are multipotent progenitor p-MTB (capable of generating myeloid, T and B cells),
      bipotent progenitors p-MT, p-MB and p-TB, and unipotent progenitors p-M, p-T and
      p-B. Among these seven types, the p-TB type progenitor was found to be absent.
      These findings indicate that the process of lineage commitment proceeds through
      an ordered but not random process. By extending the area of investigation to
      include the erythroid lineage, more convincing evidence for the ordered process
      was obtained. Detailed and exact illustration of the process of hematopoiesis
      will provide an opportunity to revive hematopoiesis as one of the most
      fascinating targets of research in developmental biology.

PMID- 11342296
TI  - Origin of hematopoietic progenitors during embryogenesis.
AB  - It has been widely accepted that hematopoietic and endothelial cell lineages
      diverge from a common progenitor referred to as the hemangioblast. Recently,
      analyses of the potential of progenitor cells purified from mouse embryos as well
      as embryonic stem cells differentiating in vitro resolved intermediate stages
      between mesodermal cells and committed precursors for hematopoietic and
      endothelial cell lineages. There are two distinct hematopoietic cell lineages
      which have different origins, i.e., primitive hematopoietic lineage derived from
      mesoderm or hemangioblasts and definitive hematopoietic lineage derived from
      endothelial cells. The endothelium is suggested to provide a milieu in which the
      definitive hematopoietic lineage acquires multiple potentials.

PMID- 11342297
TI  - Regulation of lineage commitment during lymphocyte development.

PMID- 11342298
TI  - Pax5 determines the identity of B cells from the beginning to the end of B
      lymphopoiesis.
AB  - Despite being one of the most intensively studied cell types, the molecular basis
      of B cell specification is largely unknown. The Pax5 gene encoding the
      transcription factor BSAP is required for progression of B-lymphopoiesis beyond
      the pro-B cell stage. Pax5-deficient pro-B cells are, however, not yet committed
      to the B-lymphoid lineage, but instead have a broad lymphomyeloid developmental
      potential. Pax5 appears to mediate B-lineage commitment by repressing the
      transcription of non-B-lymphoid genes and by simultaneously activating the
      expression of B-lineage-specific genes. Pax5 thus functions both as a
      transcriptional repressor and activator, depending on its interactions with
      corepressors of the Groucho protein family or with positive regulators such as
      the TATA-binding protein. Once committed to the B-lineage, B cells require Pax5
      function to maintain their B-lymphoid identity throughout B cell development.

PMID- 11342300
TI  - What can we learn from leukemia as for the process of lineage commitment in
      hematopoiesis?
AB  - Most contemporary models of hematopoiesis assume lineage fidelity of early
      progenitor cells. Along with this concept normal hematopoietic cells and the
      majority of leukemias express exclusively myeloid or lymphoid specific antigens.
      On the other hand, growing evidence exists challenging the lineage fidelity
      model. Chronic myeloid leukemia (CML) in the blast crisis may switch to acute
      lymphoblastic leukemia (ALL) and as a result of the chemotherapy ALL may converse
      to acute myeloid leukemia (AML). Furthermore, a substantial portion of leukemia
      cases, named acute mixed-lineage leukemia (AMLL), show simultaneous expression of
      both myeloid and lymphoid antigens. Immunoglobulin (Ig) and T-cell receptor (TCR)
      gene rearrangements, correlating with myeloid-lymphoid immunophenotype in AMLL,
      support the hypothesis of lineage infidelity of early progenitor cells, rather
      than the aberrant antigen expression. Based on a detailed characterization of
      AMLL we present a modified model of a "common myeloid/lymphoid progenitor cell".
      This hypothetical very early hematopoietic progenitor cell shows a transient
      expression of myeloid and B- or T-lymphoid antigen and may also have rearranged
      its Ig and/or TCR genes. Subsequently, myeloid or lymphoid markers are
      downregulated and the hematopoietic cell enters either myeloid, T-lymphoid or B
      lymphoid differentiation pathway.

PMID- 11342299
TI  - Transcription factors that regulate growth and differentiation of myeloid cells.
AB  - Recently much progress has been made in our understanding of how myeloid
      progenitor cells undergo commitment and become mature granulocytes or
      monocytes/macrophages. Studies of normal and leukemic myeloid cells as well as
      those of cells derived from mice with targeted disruption showed that a series of
      transcription factors play a major role in both commitment and maturation of
      myeloid cells. This is primarily because these transcription factors direct an
      ordered pattern of gene expression according to a well-defined developmental
      program. PU.1, an Ets family member, is one of the master transcription factors
      identified to regulate development of both granulocytes and
      monocytes/macrophages. Further, C/EBPalpha and C/EBPvarepsilon of the bZip family
      have important roles in directing granulocytic maturation. A number of additional
      transcription factors such as AML1, RARalpha, MZF-1, Hox and STAT families of
      transcription factors, Egr-1 and c-myb etc are shown to play roles in myeloid
      cell differentiation. Our laboratory has recently obtained evidence that ICSBP, a
      member of the IRF family, is involved in lineage commitment during myeloid cell
      differentiation and stimulates maturation of functional macrophages. Future
      elucidation of pathways and networks through which these transcription factors
      act in various stages of development would provide a more definitive picture of
      myeloid cell commitment and maturation.

PMID- 11342301
TI  - Derivation of dendritic cells from myeloid and lymphoid precursors.
AB  - The antigen presenting dendritic cells (DC) found in mouse and human lymphoid
      tissues are heterogeneous. Several subsets of mature DC have been described and
      these may correspond to distinct lineages. In this review, we present evidence
      obtained from a series of studies on the lineage origin of DC. This evidence
      points to the existence of at least three pathways for DC development, namely one
      from myeloid progenitors, a second from lymphoid progenitors and the third for
      Langerhans cells from precursors whose relationship to myeloid or lymphoid cell
      types is not yet clearly defined.

PMID- 11342302
TI  - The relationship of CD5+ B lymphocytes to macrophages: insights from normal
      biphenotypic B/macrophage cells.
AB  - For decades, numerous investigators have reported derivation of macrophage-like
      cells from CD5(+) pre-B cell lymphomas. Recently, it has become clear that
      biphenotypic CD5(+) B/macrophage cells are not a spurious result of malignancy.
      Indeed, the existence of normal biphenotypic cells with CD5(+) B lymphocyte and
      macrophage characteristics has been demonstrated in the mouse. This review
      considers normal B/macrophage cell function in an evolutionary context where a
      primitive, flexible cell type could perform dual roles in adaptive and innate
      immunity.

PMID- 11342303
TI  - Secondary leukaemia and myelodysplasia after autografting for lymphoma: is the
      transplant to blame?
AB  - Haemopoietic stem cell autografting is becoming a standard part of the
      therapeutic repertoire for salvage of relapsed lymphoma patients. Over the last
      five years or so a number of studies have identified that such patients are at
      high risk of developing secondary acute myeloid leukaemia (AML) or
      myelodysplastic syndromes (MDS). The actuarial risks have been estimated to be up
      to 18% in some series. More recently, studies from France and the EBMT suggest
      that in Registries containing large numbers of transplanted patients the risks
      are lower and are of the order of 3-5% at five years. Cytogenetic examination of
      bone marrow cells taken pre-transplant may also show identical abnormalities to
      those found in the leukaemic clone after transplant indicating that in many
      instances the stem cell damage was caused by prior treatment. In addition, a
      report from the British National Lymphoma Investigation has identified that post
      transplant MDS/AML was related to the total quantity of treatment received, with
      mustine being identified as a particular culprit. It thus seems probable that the
      additional stem cell insult offered by the transplant may be small although a
      factor which may increase the risk is the use of total body irradiation.

PMID- 11342304
TI  - Reactivation of human herpesviruses after allogeneic peripheral blood stem cell
      transplantation and bone marrow transplantation.
AB  - Reactivation of latent herpesviruses results in outcomes ranging from
      asymptomatic shedding of viruses to severe diseases, depending on the
      immunological competence of the host. Severe and prolonged suppression of
      cellular and humoral immunity after hematopoietic stem cell transplantation is
      accompanied by a high incidence of symptomatic recurrent herpesvirus infections.
      Subclinical reactivation also occurs more frequently than previously expected in
      transplant recipients. An increasing viral load in the blood detected by an
      antigenemia assay or PCR and viral shedding in regional fluids have a predictive
      value for subsequent diseases. Monitoring of viral DNA in the peripheral blood
      after allogeneic bone marrow transplantation (allo-BMT) reveals unique temporal
      profiles of detection for each herpesvirus. Recent studies demonstrate that
      recovery of CD4+ T cells is enhanced within one month after allogeneic peripheral
      blood stem cell transplantation (allo-PBSCT) compared to allo-BMT. To clarify
      whether this immunological advantage could affect the reactivation of human
      herpesvirus (HHV), we monitored the emergence of viral DNA by a nested-double
      polymerase chain reaction in peripheral blood leukocytes. Detection rates of HHV
      6 DNAs which peak at 3-4 weeks post-transplant, were significantly reduced after
      allo-PBSCT compared to allo-BMT, while those of other herpesviruses which tend to
      be reactivated later than this period (Epstein-Barr virus and cytomegalovirus)
      were similar between the two types of transplants. Detection of HHV-6 DNA within
      the first month after the transplant was associated with delayed platelet
      engraftment. These results underscore the important role of CD4+ T reconstitution
      in inhibiting virus reactivation post-transplant.

PMID- 11342305
TI  - TALE homeoproteins as HOX11-interacting partners in T-cell leukemia.
AB  - The mammalian PBX and Meis proteins belong to the TALE (three-amino acid-loop
      extension) superfamily of homeodomain-containing transcription factors. Members
      of both the PBX and Meis groups have been implicated in tumorigenesis and are
      known to cooperatively bind DNA with Class I (clustered) HOX homeoproteins. Here
      we show that PBX and Meis homeoproteins cooperatively bind the PBX-responsive
      sequence in vitro with the oncoprotein encoded by the non-clustered homeobox gene
      HOX11 activated by the t(10;14)(q24;q11) chromosomal translocation in T-cell
      acute lymphoblastic leukemia (T-ALL). An FPWME motif N-terminal to the
      homeodomain is required for interaction with PBX proteins, which appears to
      confer DNA-binding specificity to HOX11. PBX proteins are highly expressed in
      HOX11 immortalized/transformed hematopoietic cells; in particular, the 10q24
      translocation-carrying T-ALL Sil and K3P lines were found to selectively express
      PBX2. Ectopic retroviral-directed overexpression of PBX2 in concert with HOX11 in
      NIH3T3 cells resulted in decreased contact inhibition of growth as evidenced by
      focus formation in confluent cell monolayers. The accumulated data are thus
      consistent with a role of TALE homeoproteins in HOX11-mediated leukemogenesis.

PMID- 11342306
TI  - Biology of monocyte-specific esterase.
AB  - The monocyte-specific (carboxyl)esterase (MSE) is a marker enzyme which is well
      known to hematologists as its detection is part of the traditional cytochemical
      stainings of leukemia cells. There are a variety of synonyms for MSE among
      hematologists and biochemists. Biochemically, MSE is well-characterized, but
      should be discerned from other esterases with similar or identical substrate
      specificities and other features. Intensive analysis of normal and malignant
      hematopoietic cells and leukemia-lymphoma cell lines using isoelectric focusing
      established the specificity of this enzyme for monocytes and related cells, hence
      its designation as monocyte-specific esterase. Cloning of the gene led to its
      molecular characterization and provided new opportunities to examine MSE
      expression also at the RNA level which confirmed the monocyte/macrophage
      specificity. The availability of the gene sequences of various serine esterases
      and lipases which also hydrolyze ester bonds allowed for the identification of
      identical isolates from different tissues and the construction of an unrooted
      dendrogram based on sequence homologies of 22 enzymes. The detailed regulation of
      the gene and the functional role of MSE have remained largely unknown as of yet.
      However, DNA binding sites for various transcription factors have already been
      detected. Some evidence suggests involvement in physiological detoxification
      processes and in the immune defense against tumor cells. A more thorough
      understanding of the in vivo function of this truly unique enzyme should be
      helped by characterizing the signals and signal transduction mechanisms which
      lead to MSE expression.

PMID- 11342307
TI  - Retinoic acid receptor alpha (RAralpha) Mutations in Human Leukemia.
AB  - The retinoic acid receptor alpha (RARalpha) plays a central role in the biology
      of the myeloid cellular compartment. Chromosomal translocations involving the
      RARalpha locus probably represent the malignant initiating events in acute
      promyelocytic leukemia (APL). Recent studies that identify novel interactions
      between RARalpha and the nuclear receptor co-activators and co-repressors, new
      functions of the oncogenic RARalpha fusion proteins and their catabolism in
      retinoic acid-induced differentiation, and the availability of new transgenic
      mice models have provided important insights into our understanding of the
      mechanisms by which mutant forms of RARalpha can be implicated in the development
      of leukemia. Novel alterations of the RARalpha gene identified in hematopoietic
      malignant disorders other than APL, such as myelodysplastic syndromes, non-APL
      acute myeloid leukemias and B-chronic lymphocytic leukemias, suggest that
      disruption of the RARalpha gene might predispose to myeloid and lymphoid
      disorders.

PMID- 11342308
TI  - Prolonged disease-free survival after autografting for chemosensitive non-bulky
      low grade non-Hodgkin's Lymphoma.
AB  - The results of autografting in patients with relapsed low grade non-Hodgkin's
      Lymphoma (NHL) have generally been disappointing due to the failure to maintain
      remission and the late development of myelodysplasia. Most series have used
      regimens that include total body irradiation and purged stem cells. We evaluated
      the outcome in 32 patients with low grade NHL autografted using chemotherapy-only
      busulfan-based conditioning and unpurged stem cells. Seven of 10 patients with
      poor prognostic features at diagnosis remain alive in CR a median of 78 months
      (range 14-129) post-transplant. Twenty two patients with relapsed,
      chemosensitive, low bulk disease, most of whom did not have marrow involvement or
      an elevated LDH, were transplanted. Only five of the 22 have relapsed, with an 86
      +/- 8% overall survival and 72 +/- 10% event free survival (EFS) after a median
      follow-up of 56.5 months. All but one patient has an EFS period longer, often
      substantially so, than their previous longest remission. No patient has developed
      myelodysplasia. These data suggest that in selected patients with poor prognosis
      or relapsed low grade NHL autografting has a favourable impact on the natural
      history of their disease and may result in long-term disease control.

PMID- 11342309
TI  - Infusional vinorelbine in relapsed or refractory lymphomas.
AB  - Vinorelbine (Navelbine is a semisynthetic vinca alkaloid devoid of serious
      neurotoxicity. When given weekly vinorelbine has documented activity against many
      tumors, including lymphomas. Since weekly schedules cannot be easily incorporated
      in combination regimens, we tested an infusional schedule of vinorelbine given
      every 21 days in adults with relapsed or refractory lymphoma. Patients with
      inadequate organ or bone marrow reserve, HIV or other serious infection, central
      nervous system disease, or prior stem cell or bone marrow transplantation were
      ineligible. In the phase I part, patients received a constant intravenous bolus
      of 8 mg/m(2), followed by intravenous continuous infusion over 24 hours daily for
      four days increasing from 10, 12, to 14 mg/m(2) /d in successive three-patient
      cohorts. Cycles were repeated every 21 days, and the daily continuous infusion
      dose was adjusted for toxicity. Dose-limiting mucositis and neutropenia were
      reached at the continuous dose of 14 mg/m(2) /d. Consequently, for the Phase II
      trial the starting continuous infusion dose was 12 mg/m(2) /d. After the first 19
      patients were entered in the phase II study, the starting infusion dose was
      reduced to 10 mg/m(2) /d because of frequent grade (3/4) myelosuppression and
      mucositis. Forty-four patients were entered in the phase II study, of whom 41 are
      evaluable. Median age was 61 years, 23 were males, with clinically aggressive non
      Hodgkin's lymphoma (NHL) in 22, indolent NHL in 18, and Hodgkin's Disease in one
      patient. The median number of prior regimens was 3 (range 1-11). The lymphoma was
      refractory to the initial regimen in nine patients, and to the regimen
      immediately before vinorelbine in 20 patients. Serum LDH was high in 2(1/4)1, and
      serum beta(2) -microglobulin > 3.0 mg / L in 16/31 patients. Responses were
      observed in four of 22 patients with aggressive NHL (18%, 95% confidence interval
      5%-40%), and in six of 18 with indolent NHL (33%, 95% confidence interval 13%
      59%). Median progression-free survival was 6 months for responders. During the
      Phase II trial 114 vinorelbine courses were administered. Neutrophil nadir was <
      1000/microl in 65% and < 100/microl in 35% of courses, respectively. Platelet
      nadir was < 100,000/microl in 30% and < 20,000/microl in 8% of courses,
      respectively. Grade (3/4) mucositis was seen in 18% of courses, and neutropenic
      fever in 13%, and was complicated by death in one patient. We conclude that this
      dosage and schedule of vinorelbine has modest activity in patients with relapsed
      or refractory NHL. Myelosuppression is frequent but reversible, but there is no
      significant neurotoxicity. The role of vinorelbine in combination regimens for
      patients with relapsed lymphomas, particularly those of indolent histology,
      should be further investigated.

PMID- 11342310
TI  - Is there any difference in PBPC mobilization between cyclophosphamide plus G-CSF
      and G-CSF alone in patients with non-Hodgkin's Lymphoma?
AB  - We attempted to analyze whether the use of high-dose cyclophosphamide (CTX 7g/m2,
      group A) plus hematopoietic growth factor (G-CSF) or G-CSF alone (10 microg/Kg,
      group B) as a mobilizing regimen, could result in harvesting different numbers of
      CD34+ cells, committed progenitors and CD34+ cells subsets. The number of CD34+
      cells considered as the target for each high-dose chemotherapy was > or = 2 x
      10(6) /Kg/bw. Fifteen leukaphereses procedures were necessary in group A, while
      16 procedures were performed in group B. We did not observe any difference
      between the two groups in terms of CD34+ cells/microl in the peripheral blood
      (117 vs 78; p = NS), whereas in the aphereses product we found a significant
      difference between the two groups of patients in terms of CD34+ cells (6.41 vs
      2.89 x 10(6) /Kg/bw; p = .009), CFU-GM (82.5 vs 52.3 x 10(4) /Kg/bw; p = .04).
      Interestingly, we noted a different distribution of CD34+/33- cells between the 2
      groups (mean value 39% vs 65%; p < .05), whereas we did not find any differences
      regarding CD34+/38-, CD34+/Thy1+, CD34+/HLADR-. The higher number of CFU-GM/Kg/bw
      collected in the former group did not translate into a superior plating
      efficiency (27.75 vs 30.29). Furthermore, we observed a strong correlation
      between CD34+ cells/microl in the peripheral blood and the total number of CD34+
      cells in the leukaphereses product (r = 0.97), whereas this correlation was not
      found in group B (r = 0.15). In both groups of patients the number of CD34+ cells
      collected correlated well with CFU-GM (r = 0.93; r = 0.94), but definitely we did
      not observe any correlation between CD34+ cells/microl and CFU-GM in patients
      mobilized with G-CSF alone and this did not allow us to predict the harvest
      accurately. Finally, we evaluated the engraftment kinetics and we did not observe
      any statistically significant difference between the two groups of patients.

PMID- 11342311
TI  - Second lethal events associated with treatment for Hodgkin's disease: a review of
      2980 patients treated in a single Mexican institute.
AB  - Presence of second neoplasms and cardiac toxicity has been recognized as
      potential late lethal second events in patients treated for Hodgkin's disease.
      However, most reports analyze these association independently. We reviewed 2980
      cases of patients treated during 1970-1995 with long-term follow-up (> 4 years)
      in an attempt to identify all late events in Hodgkin's disease secondary to the
      treatment or those which are unrelated. Three hundred and ten patients died, and
      of these 156 were secondary to relapse and tumor progression. Death associated
      second tumors and cardiac events were increased 37 fold and 29 fold respectively
      compared to the general population. The risk factors for this complications did
      not differ to previous reports and included alkylating agents and/or radiotherapy
      for second neoplasms and anthracycline therapy and radiotherapy for cardiac
      toxicity. Moreover, 61 patients died secondary to non-related events.
      Nevertheless, at 20-years overall survival was 90 % (95 % confidence interval
      (CI): 78 % to 97 %) and event free survival was 88 % (95 % CI: 76 % to 96 %) for
      these patients. Thus, second events, fatal in most cases, should be considered as
      an expected risk to the treatment in patients with Hodgkin's disease; the
      proposed modifications of therapy may indeed be useful to avoid or diminish these
      complications in the future.

PMID- 11342312
TI  - Circulating and tumor-infiltrating gamma delta T Cells in patients with B-cell
      lymphomas.
AB  - In order to analyze the involvement of gamma delta T cells in the immune
      surveillance against B cell lymphomas (BCL), we investigated the proportion of
      circulating gamma delta T cells in 52 BCL patients using two-color flow
      cytometry, together with tumor-infiltrating gamma delta T cells in 22 of those
      patients. We found that the proportion of tumor-infiltrating gamma delta T cells
      in BCL patients was not different from that of lymph node gamma delta T cells in
      reactive hyperplasia patients. However, a decreased percentage of circulating
      gamma delta T cells were observed in indolent lymphoma (IL) and limited
      aggressive lymphoma (AL) patients when compared with normal controls. In
      contrast, as a result of a histogram, advanced AL patients were divided into two
      subgroups: the patients with increased circulating gamma delta T cells and those
      without any increase. However, there was no difference in the clinical features
      of between the two AL subgroups.

PMID- 11342314
TI  - Screening of Bcr-Abl transcripts in Philadelphia negative essential
      thrombocythemia.
AB  - Essential thrombocythemia (ET) is a chronic myeloproliferative disorder
      characterised by the absence of the Philadelphia (Ph+) chromosome. Recent studies
      have reported controversial results relating to BCR-ABL rearrangements in ET
      patients. We studied 44 Ph-negative ET patients with the RT-PCR technique at
      diagnosis or during the follow-up. None of them showed any of the BCR-ABL
      transcript actually described by others in ET; neither the "classical" P210 nor
      the P190 or P230 variants. Our results confirm the absence of BCR-ABL
      abnormalities in Ph-negative ET patients.

PMID- 11342313
TI  - Association of Burkitt's lymphoma with the Epstein-Barr virus in two developing
      countries.
AB  - The clinical presentation of Burkitt's lymphoma (BL) and it's association with
      the Epstein-Barr virus (EBV) varies in different geographic areas, BL in
      developing countries being "intermediate" between the sporadic and endemic types,
      both in it's clinical presentation and it's association with EBV, which varies
      from 25-80%. In this study we have analysed the clinical features, EBV
      association, subtype and prevalence of the deleted variant of the Latent Membrane
      Protein-1 (LMP-1) of EBV in forty-two cases from two developing countries- India
      (n = 25) and Argentina (n = 17). In both countries the abdomen was the site most
      commonly involved while jaw involvement was rare. EBV was detected by in-situ
      hybridization using the EBER-1 RNA probe. 47% of cases from Argentina and 80% of
      cases from India were EBER positive. EBV typing using EBNA-3C primers showed a
      predominance of Type A in both countries (India-13/16 and Argentina-(7/8)). The
      30bp deletion of the LMP-1 gene was detected in all evaluated cases from
      Argentina while the wild type of the gene was seen in all the evaluable Indian
      cases. Our study highlights the similarities and differences in the clinical
      presentation and EBV association of BL in two developing countries and also
      indicates that the subtype of EBV and prevalence of the LMP-1 deletion may
      reflect the predominant subtype in a particular population.

PMID- 11342315
TI  - Cathepsin inhibition induces apoptotic death in human leukemia and lymphoma
      cells.
AB  - We examined the effects of cathepsin inhibitor 1 (CATI-1), a selective inhibitor
      of cysteine cathepsins, on human leukemia and lymphoma cells. CATI-1 induced
      apoptosis in all 12 cell lines tested. Apoptosis of CATI-1-treated
      leukemia/lymphoma cells was caspase-independent, p53-independent, BAX-independent
      as well as MAP kinase-independent. Our findings provide unprecedented
      experimental evidence that cathepsins play a pivotal role for the survival of
      human leukemia/lymphoma cells. Therefore, cathepsin inhibitors may provide the
      basis for new treatment programs against leukemia and lymphoma.

PMID- 11342316
TI  - Decrease of circulating hematopoietic progenitor cells During interleukin-2
      treatment is associated with an increase of vascular cell adhesion molecule-1, a
      critical molecule for progenitor cell adhesion.
AB  - Administration of interleukin-2 (IL-2) to cancer patients has been shown to
      transiently decrease the number of circulating hematopoietic progenitor cells,
      but the mechanism of this phenomenon is unknown. Recently, the interaction of
      vascular adhesion molecule-1 (VCAM-1) with leukocyte very late antigen-4 (VLA-4)
      has been demonstrated to play a crucial role in the adhesion of progenitor cells
      to bone marrow stromal elements. Cytokine induced upregulation of VCAM-1 leads to
      increased binding of progenitor cells to stromal cells in vitro, and inhibition
      of this interaction by monoclonal antibodies is associated with marked progenitor
      cell mobilisation in vivo. In the present study we serially determined peripheral
      blood progenitor cell numbers during IL-2 treatment (10 courses) in 6 cancer
      patients and determined in parallel levels of soluble VCAM-1 as a surrogate
      marker for the in vivo activation of this molecule. Our data indicate that
      continuous intravenous administration of IL-2 for 5 days leads to a marked
      decrease of circulating progenitor cells associated with a substantial increase
      of circulating VCAM-1. Circulating myeloid progenitor cells (CFU-GM) dropped from
      a mean value of 167 +/- 187 / ml pre IL-2 to 16 +/- 15 / ml on day 3 (p < 0.01).
      Similarily, mean erythroid progenitors (BFU-E) decreased from 282 +/- 204 / ml
      before IL-2 administration to 86 +/- 61 / ml on day 3 (p < 0.005). In contrast,
      soluble VCAM-1 rose from a mean value of 1814 +/- 451 ng/ml before to 4607 +/-
      736 ng/ml at the end of IL-2 therapy (p < 0.0001). Sera from IL-2 treated
      patients did not inhibit hematopoietic colony formation from normal bone marrow.
      These results suggest redistribution and increased adhesion of progenitor cells
      to stromal and/or endothelial elements during IL-2 via the VCAM-1/VLA-4
      interaction as a possible mechanism for the decrease of circulating progenitor
      cells during IL-2 therapy.

PMID- 11342317
TI  - Sex steroid receptors in Hodgkin's disease.
AB  - A case report of a dramatic therapeutic response of Hodgkin's disease (HD) to
      diethylstilbestrol (DES) in a man who was being treated for concurrent prostate
      cancer suggested that there also may be a role for sex steroids in the
      pathogenesis of HD (1). High levels of estrogen receptors (ER) comparable to
      those seen in breast carcinoma cells were detected in that patient's Hodgkin's
      biopsy specimen. In order to determine whether this patient was unique or whether
      sex steroid receptors commonly are present in HD specimens, we examined
      expression of ER and progesterone receptors (PR) in diagnostic tissue from
      pediatric (n = 14) and adult (n = 41) patients with HD using
      immunohistochemistry. None of the 55 samples expressed PR. 16/55 (29%)
      demonstrated weak nuclear ER positivity, which was confined to germinal center
      and occasional mantle zone lymphocytes and was comparable to that seen in non
      malignant control lymph nodes. (4/5)5 (7.3%) samples exhibited moderate
      positivity in Reed Sternberg cells, which in one case was nuclear. ER commonly
      are expressed weakly in some HD tumors unrelated to clinical stage or patient sex
      but are generally limited to germinal center and mantle zone lymphocytes. A rare
      patient displays moderate cytoplasmic or nuclear ER in Reed-Sternberg cells.

PMID- 11342318
TI  - Establishment of a myeloid cell line, YM711, characterized by retinoid
      resistance.
AB  - A myeloid cell line (YM711) was established by transfecting exogenous
      PML/RARalpha cDNA into peripheral blood stem cells. The cells were positive for
      CD33, CD34, CD38, CD13, CD14, and CD11b. Cytochemical examination revealed YM711
      cells to be positive for peroxidase, alpha-naphtyl butyrate esterase, and acid
      phosphatase as well. Karyotypic analysis showed them to be nearly tetraploid (92
      XXYY). Reverse-transcription polymerase chain reaction showed that, although
      PML/RARalpha mRNA was detected in YM711, these cells could not be differentiated
      by all-trans retinoic acid (ATRA). We therefore designated the YM711 cell line as
      being ATRA resistant. Because YM711 expressed multi drug resistance 1 (MDR-1)
      mRNA and p-glycoprotein cell surface protein, we assessed whether verapamil and
      ATRA would induce the differentiation of YM711 cells; they did not. An increased
      expression of cellular retinoic acid-binding protein (CRABP)-II was also detected
      on YM711 cells compared with that of HL-60. These results suggest that high level
      of expression of CRABP-II may contribute to be the mechanism of ATRA resistance.
      This cell line may be useful in evaluating the mechanism of resistance to
      retinoid.

PMID- 11342319
TI  - Consistent loss of heterozygosity at 14Q32 in lymphoid blast crisis of chronic
      myeloid leukemia.
AB  - Little is understood about the basic biological mechanisms that underlie the
      reasons for acute transformation in chronic myeloid leukemia (CML). Progression
      of disease may include inactivation of one or more tumor suppressor genes (TSGs).
      A widely used methodology for indirectly detecting somatic inactivation of TSGs
      is searching loss of heterozygosity (LOH) for polymorphic loci located in or near
      the gene(s) of interest. We aimed to analyze DNA of chronic phase and blastic
      phase archive material of 15 CML patients for LOH using D1S430, D2S123, D3S1611,
      D11S29, D14S65, D17S520, BAT 40 markers, the dinucleotide repeat located in the
      ABL gene and the trinucleotide repeat located in the BCR gene (amplification of
      the trinucleotide in the BCR gene could not be succeeded). LOH was identified by
      a %50 lost of one of the alleles intensity. LOH was detected with the ABL
      dinucleotide repeat and D2S123 marker in two patients and with the D14S65 marker
      in three patients. The three patients exhibiting LOH at the D14S65 locus, all
      proceeded through lymphoid blast crisis. The D14S65 marker is located at the
      14q32 locus which contains the immunoglobulin heavy chain gene and the TCL1
      oncogene. 14q32 abnormalities at the molecular level, may be predictive for
      lymphoid blast crisis, whether or not they are detectable cytogenetically.

PMID- 11342320
TI  - Fish demonstrates treatment-related chromosome damage in myeloid but not plasma
      cells in primary systemic amyloidosis.
AB  - Conventional cytogenetic analysis is limited in the evaluation of plasma cell
      disorders because, relative to normal hematopoietic elements, plasma cells divide
      slowly. Moreover, it is difficult to know whether abnormal metaphases originate
      from malignant plasma cells or myeloid cells harboring other abnormalities. We
      studied a patient with primary systemic amyloidosis who had previously been
      treated with an alkylating agent. Bone marrow cells were analyzed by cytoplasmic
      immunoglobulin fluorescent staining combined with fluorescent in situ
      hybridization (cIg-FISH). Both chromosome enumeration probes for chromosome 1 and
      7 and loci-specific probes for the short and long arm of chromosome 7 were used.
      Cytogenetic analysis disclosed the following abnormality: +der(1;7)(q10;p10). On
      cIg-FISH, the myeloid cells had fusion signals between chromosome enumeration
      probes for chromosomes 1 and 7, whereas plasma cells had the normal appearance of
      two pairs of signals. There was a second clone of abnormal myeloid cells with
      monosomy of chromosome 7. The bone marrow did not show any evidence of
      myelodysplasia. Interphase cIg-FISH is a useful technique for assigning the
      lineage of chromosomal abnormalities in plasma cell disorders.

PMID- 11342321
TI  - Non-caseating granulomata associated with hypocellular myelodysplastic syndrome.
AB  - Non-caseating granuloma (NCG) remains a histopathological hallmark for
      sarcoidosis. Although the exact mechanism for NCG formation is unknown, the
      pathogenesis may involve a disordered antigen presentation in the
      monocyte/macrophage system, functional abnormalities in activated T-lymphocytes
      and uncontrolled cytokine production. Similar immunological dysfunction has been
      described in myelodysplastic syndrome (MDS). However, the association of NCG and
      MDS is rarely documented. We report a case of hypocellular MDS associated with
      generalized NCG. Despite treatment for both sarcoidosis and tuberculosis, the
      patient failed to respond. A clonal myeloid disorder which was initially
      suppressed by T-cell immunosurveillance evolved after treatment with anti
      thymocyte globulin. Although the coexistence of sarcoidosis remains a
      possibility, the lack of supportive clinical evidence of sarcoidosis, the
      abnormal appearances of the bone marrow, together with the failure to improve on
      high-dose steroid favour the clonal myeloid disorder as the sole pathology.

PMID- 11342322
TI  - Trisomy 10 as the sole abnormality in biphenotypic leukemia.
AB  - We observed a case of acute biphenotypic leukemia with trisomy 10 as the sole
      abnormality. The patient was an adult male diagnosed with ALL(L2), Cell marker
      studies showed positivity for CD3, CD7, CD13 and CD33, so the phenotypic
      diagnosis was determined to be biphenotypic leukemia. No case of biphenotypic
      leukemia with trisomy 10 has been previously reported, until now.

PMID- 11342323
TI  - Successful treatment of aggressive post transplant lymphoproliferative disorder
      using rituximab.
AB  - A 52 year -old female developed a histologically aggressive, Epstein-Barr virus
      positive, lymphoproliferative disorder involving the brain and liver 4 months
      following a combined kidney/pancreas transplant. Following a brief trial of
      reduced immunosuppression, she was treated with rituximab. Despite subsequent re
      intensification of immunosuppression, the lesions showed continued regression
      with almost complete disappearance by 5 months. Rituximab appears to be a safe,
      effective treatment for post transplant lymphoproliferative disorder.

PMID- 11342324
TI  - Varicella zoster meningitis preceeded by thrombophlebitis in a patient with
      Hodgkin's disease.
AB  - Varicella zoster (V-Z) infections are common among patients with hematological
      malignancies, particularly Hodgkin's disease (HD). The common denominator in both
      HD and V-Z infections is immunosuppression. Most of V-Z infections occur in
      patients with HD during the remission period, who have mixed cellularity sub
      type, with stage III disease and who have received combined chemo-radiation
      therapy. Involvement of the central nervous system usually manifests as post
      herpetic neuralgia or encephalitis. Angiitis has also been found in association
      with V-Z infections. The authors describe a case of HD who developed V-Z
      meningitis preceeded by superficial thrombophlebitis of upper extremities during
      the period of active chemotherapy.

PMID- 11342325
TI  - Idiopathic myelofibrosis developing isolated granulocytic sarcoma with der
      (1;7)(q10; p10) after splenectomy and finally transforming to acute myelogenous
      leukemia.
AB  - A 47-year-old female with idiopathic myelofibrosis developed isolated
      granulocytic sarcoma with der (1; 7)(q10; p10) after splenectomy, followed by
      acute myelogenous leukemia. The patient had myelofibrosis since 22 years of age,
      received splenectomy at 47 years, and developed isolated submandibular
      granulocytic sarcoma, 8 months later. Although the initial tumor disappeared
      after irradiation, recurrent tumors selectively appeared in the areas of
      operative scars. She subsequently developed blastic transformation with der (1;
      7)(q10; p10), and the blasts were refractory to different chemotherapy. This case
      is very rare in the following aspects: the onset of myelofibrosis occurred at a
      relatively young age; isolated granulocytic sarcoma after splenectomy preceded
      the transformation to acute leukemia; and the subcutaneous tumors developed in
      areas of operative scars.

PMID- 11342326
TI  - Nodal T cell blast crisis in chronic myeloid leukemia.
AB  - We report the case of a 54 year old male with an original diagnosis of chronic
      myeloid leukemia (CML) who developed a nodal T cell blast crisis (BC) while he
      was in a complete hematological remission (CR). We describe the clinical
      presentation and the histological, immunophenotypic and molecular
      characterization of the lymph node blast cells. Our case, together with other
      rare similar reports in the literature, argue that a T cell nodal blast crisis of
      CML resembles the presentation of a T-cell non-Hodgkin's lymphoma.

PMID- 11342327
TI  - Vaccination of a refractory essential monoclonal cryoglobulinemia patient with
      cryoglobulin-pulsed dendritic cells.
AB  - We vaccinated a refractory essential monoclonal cryoglobulinemia patient with
      monocyte-derived DCs (Mo-DCs) pulsed with purified cryoglobulin as a tumor
      antigen. During the vaccinations, his acrocyanosis improved and we were able to
      reduce the number of hot baths used to treat his symptoms, with no side effects.
      Furthermore, cryoglobulin-specific proliferative responses were observed after
      the vaccination. As there was a recurrence of acrocyanosis after the final
      vaccination, vaccination with Mo-DCs pulsed with purified cryoglobulin would seem
      to be a useful treatment for refractory essential monoclonal cryoglobulinemia.

PMID- 11342328
TI  - The nuclear migration gene NudC and human hematopoiesis.
AB  - The filamentous fungus Aspergillus nidulans nudC (nuclear distribution C) gene is
      required for movement of nuclei following mitosis and for normal colony growth.
      It is highly conserved, structurally and functionally, throughout most of
      evolution. The human homolog, called HnudC, has been cloned and has an important
      role in cell proliferation. In hematopoiesis, HNUDC is highly expressed in early
      hematopoietic precursors and declines during normal differentiation. Stimulation
      of proliferation of the erythroleukemia cell line TF-1 with GM-CSF enhances HnudC
      protein and mRNA expression and treatment with antisense (but not sense)
      oligonucleotides to HnudC mRNA significantly reduces cell division. A significant
      increase in HNUDC is present in bone marrow aspirates from patients with acute
      lymphoblastic leukemia (ALL) and acute myelogenous leukemia (AML) compared to the
      level in normal cellular counterparts, demonstrating dysregulated expression in
      leukemia. These data support the conclusion that HnudC plays a functional role in
      promoting hematopoietic cell growth and that it is involved in leukemogenesis.

PMID- 11342329
TI  - The use of cytotoxic t cells for the prevention and treatment of epstein-barr
      virus induced lymphoma in transplant recipients.
AB  - Epstein-Barr Virus Lymphoproliferative Diseases (EBV-LPD) can affect patients
      receiving allogeneic hemopoietic stem cell or solid organ transplant. They are
      caused by impairment of EBV specific CD8+ cytotoxic T-lymphocyte (CTL) response
      due to the immunosuppression that follows these procedures. Despite different
      therapies LPD can still have a rapid and lethal course. A promising solution is
      the application of adoptive immunotherapy approaches such as ex vivo generated
      EBV-specific CTLs for prevention and therapy. Their infusion has been
      demonstrated to be safe and effective in allogeneic hemopoietic stem cell
      transplant recipients and their use after allogeneic solid organ transplant is
      also under evaluation.

PMID- 11342330
TI  - Clinical and epidemiological features of acute lymphoblastic leukemia following a
      previous malignancy.
AB  - Secondary malignancies represent a relevant complication of chemotherapy employed
      for a previous cancer. Acute leukemias represent the most frequent secondary
      malignancy in the first decade following primary neoplasms; secondary leukemias
      are generally myeloid and can be preceeded by a myelodysplastic syndrome. The
      biological and epidemiological characteristics of secondary acute myeloid are
      well known and have been the subject of numerous reports and reviews in the last
      few years. The observation of a secondary acute lymphoblastic leukemia is
      considered rare, and the correlation with antecedent therapies is not definitive.
      Most of reported cases are single reports, and no large study has been performed
      to investigate the real importance of this problem. In this review we report data
      of the current literature on secondary acute lymphoblastic leukemia, both in
      adults and children, in order to analyze its incidence and clinical and
      laboratory features.

PMID- 11342331
TI  - Biology of tartrate-resistant acid phosphatase.
AB  - Tartrate-resistant acid phosphatase (TRAP) is a member of the ubiquitously
      expressed enzyme family of the acid phosphatases. Nearly 30 years ago, TRAP
      became known to hematologists as cytochemical marker enzyme of hairy cell
      leukemia. Physiologically, TRAP is primarily a cytochemical marker of
      macrophages, osteoclasts and dendritic cells. TRAP is localized intracellularly
      in the lysosomal compartment. Recent data suggest also secretion of TRAP by some
      cell types, in particular by osteoclasts. Human, mouse and rat TRAP are
      biochemically well characterized. While the complete genomic sequence of TRAP has
      been elucidated, only limited information on the genetic details of the gene and
      its regulation is available. It appears that the intracellular iron content is
      involved in the regulation of the enzyme. The physiological substrates for this
      enzyme have not been identified yet and consequently the functional role of TRAP
      remains completely unknown, though some hypotheses have been forwarded, e.g.
      involvement in bone resorption and iron homeostasis (transport, metabolism).
      Taken together, research on the biology of TRAP has been intensive and has led to
      considerable progress on a number of fronts, including the cloning of the gene.
      Further studies are, however, still required to determine the role of TRAP in
      vivo.

PMID- 11342332
TI  - Matrix metalloproteinases and their tissue inhibitors - expression, role and
      regulation in human malignant non-Hodgkin's lymphomas.
AB  - Human malignant non-Hodgkin's lymphomas (NHL) represent a heterogeneous group of
      neoplasms, which vary in their clinical behavior and pathophysiology. Matrix
      metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) have been shown to
      play a role in the pathophysiology and clinical aggressiveness of human NHL. In
      this setting, MMP-9 and TIMP-1 appear to be the most important members of the MMP
      and TIMP families, and overexpression of both correlates with a poor clinical
      outcome of patients with NHL. MMP-9 and TIMP-1, however, act through different
      mechanisms and are produced by different cell types. Expression of both is
      upregulated by interleukin-6 (IL-6), a cytokine that is known as one of the
      factors involved in the pathophysiology of human NHL. In this review we summarize
      the complex regulation of MMP and TIMP expression in human NHL and propose a
      mechanism by which MMP-9, TIMP-1 and IL-6 may influence the biology of these
      tumors.

PMID- 11342333
TI  - Marrow transplants from unrelated donors as treatment for acute leukemia.

PMID- 11342334
TI  - Characterization and outcome of "hard to mobilize"' lymphoma patients undergoing
      autologous stem cell transplantation.
AB  - A "hard to mobilize" patient was defined as one in whom >or= 1x10(6) CD 34+
      cells/kg cannot be obtained after two consecutive large volume aphereses. Forty
      four consecutive Hodgkin's and non-Hodgkin's lymphoma patients who underwent
      autologous peripheral blood stem cell (PBSC) transplant treatment between June
      1996 and June 1998 were included in this study. Twenty-one patients (48%) met the
      definition of "hard to mobilize" (Group I). All the rest of the patients (n=23)
      were the good mobilizers (Group II). The initial mobilization protocol for most
      patients was 10 microg/kg of G-CSF alone for both groups. For Group I, 7/21 (33%)
      patients were unable to achieve a minimal dose of >or= 1x10(6) CD34+ cells/kg
      even after a second mobilization attempt and/or bone marrow (BM) harvest (n=5).
      Overall, 11/21 (52%) required an additional mobilization and/or BM harvest. Only
      3/21 (14%) patients were able to meet the target cell dose of >or= 2.5x10(6)
      CD34+ cells/kg (median of 4 apheresis). In contrast, 87% of Group II achieved the
      target dose with a median of 2 aphereses. Predictors of poor mobilization were
      greater than two prior treatment regimens (p=0.038) and the WBC count
      (<25,000/microL) on the first day of apheresis (p=0.053). Nineteen patients in
      Group I and all Group II completed treatment with a median time to engraftment of
      ANC>500/microl of 12 and 11 days, and platelet >20x10(3)/microl of 31 and 13
      days, respectively. Outcome analysis revealed that 6/19 patients in Group I died
      of relapse within one year from transplant compared with only 2/23 of Group II
      who died of relapse (p=0.005, log rank test). There were no treatment related
      deaths in either group. Independent predictive features for "hard to mobilize"
      patients are a lack of significant increase in WBC count on the first day of
      apheresis and the number of prior treatment regimens. Poor mobilization appears
      to predict a worse outcome after autografting for lymphoma patients.

PMID- 11342335
TI  - Acute myeloid leukemia in the elderly: results of an individualized approach in
      two centres.
AB  - We retrospectively assessed seventy-four consecutive patients with AML over 65
      years of age (median 71; range 65-88) treated with an individualized approach in
      two specialized cancer centers. Patients were managed according to their
      performance status (PS) and associated diseases in both institutions. The
      proportion of patients with poor PS (3-4) was higher in center 1 (37%) than in
      center 2 (10%) and in center 1 palliative treatment was given more frequently
      (16/32 patients) than in center 2 (7/42 patients). Fifty-one patients received
      intensive combination chemotherapy including an anthracycline and ara-C or VP16
      (2 patients) and 36 patients received a second intensive course as reinduction or
      as consolidation treatment after complete remission. Patients not eligible for
      myelosuppressive chemotherapy were treated with palliative measures (23
      patients). With intensive chemotherapy, complete remission (CR) was achieved in
      29 of 51 patients (57%), after first (20 patients) or second course (9 patients)
      and the rate of deaths during induction was 14% (7 patients). The CR rate was
      lower for patients with performance status >or= 2 (48%) as compared to patients
      with performance status <or= 1 (78%) and for patients with secondary AML (46%) as
      compared to patients with de novo AML (60%). Median survival was 9.1 months for
      patients receiving intensive treatment and 1.2 months for patients receiving
      palliative treatment (P=0.001). In the Cox model for overall survival, treatment
      with curative intent was associated with longer survival (hazard ratio: 0.33, 95%
      confidence interval: 0.18-0.58) and poor performance status (PS >or= 2) was
      associated with reduced survival (hazard ratio: 3.29, 95% confidence interval:
      1.75-6.17). Overall 2-years and 5-years survival were 20% and 11% for the
      patients treated intensively. From this study it appears that an individualized
      approach of treatment with intensive chemotherapy for selected patients offers a
      substantial CR rate and an improvement in survival. This analysis also suggests
      that differences in outcome between single institutions can be explained mainly
      by referral and selection biases

PMID- 11342336
TI  - Non-Hodgkin's lymphoma subtypes over time in an unselected population of 646
      patients: a study of clinico-pathological data and incidence based on a review
      using the REAL-classification.
AB  - Biopsies from 646 consecutive unselected cases of non-Hodgkin's lymphoma from a
      Danish population-based registry were reclassified according to the REAL
      classification 1) to study the distribution of subtypes over time, and 2) to
      correlate a number of clinical parameters with the various subtypes. Two cohorts
      from 1986 and 1992, of 292 and 354 cases, respectively, were studied. From 1986
      to 1992 diffuse large B-cell lymphoma showed a change in incidence of + 43.1%, as
      opposed + 2.5% for all other subtypes combined (p = 0.05), suggesting that the
      increasing general incidence of non-Hodgkin's lymphoma is due primarily to an
      increasing incidence of diffuse large B-cell lymphoma. A higher rate of cell
      proliferation was associated with an increasing chance of having extranodal
      disease. For the various subgroups there was good agreement between survival and
      the International prognostic index.

PMID- 11342337
TI  - 18-FDG-PET as a prognostic indicator in the treatment of aggressive Non-Hodgkin's
      Lymphoma-comparison with CT.
AB  - Less than 50% of newly diagnosed patients with aggressive histology Non-Hodgkin's
      Lymphoma (NHL) are cured with standard treatment. The ability to accurately
      monitor response to treatment is crucial in order to select out patients who need
      more intensive or salvage treatment. This study assesses the accuracy of FDG-PET
      as compared to CT in remission assessment following treatment of aggressive NHL,
      and its value in estimating relapse-free survival. It also evaluates the
      prognostic value of early interim PET scan in prediction of treatment outcome.
      Forty-nine adult patients with biopsy-proven aggressive NHL between September
      1993 and December 1997 were included. All patients had pre-treatment FDG-PET
      demonstrating increased uptake in sites of disease. Forty-five patients had a
      post-treatment PET to assess remission status and 4 had an interim but not a post
      treatment PET. Thirty-three of these patients also had a pre- and a post
      treatment CT scan. Twenty-three of the 49 patients had an interim PET during
      chemotherapy to assess early response. PET and CT scan results were correlated
      with relapse data to examine their accuracy in remission assessment and
      prediction of prognosis. The median follow-up duration is 30 months. Overall the
      result of post-treatment PET scan appears to predict disease outcome, with
      relapse rates of 100% (9/9) and 17% (6/36) for positive and negative PET
      respectively [p<0.001]. In a subgroup of 33 patients, direct comparison of post
      treatment PET and CT shows that PET was more accurate than CT in assessing
      remission status following treatment. Relapse rate was 100% for positive PET and
      only 18% for negative PET (p<0.001), compared to 41% and 25% for patients with
      positive and negative CT respectively (p>0.1). PET was particularly useful in
      assessment of residual masses seen on CT scan. The interim PET provided valuable
      information regarding early assessment of response and long-term prognosis, with
      no relapses in patients with no or minimal residual uptake compared to 87.5%
      relapse rate in patients with persistent PET activity (p<0.001). FDG-PET is an
      accurate method of assessing remission and estimating prognosis following
      treatment of aggressive NHL, with positive and negative predictive accuracies of
      100% and 82% respectively. PET is more accurate than CT in assessing remission
      and prediction of relapse-free survival. An interim PET scan after 2-3 cycles of
      chemotherapy predicts the long-term outcome early-on and has a high negative
      predictive value (100%). This may assist to separate at an early stage good
      prognosis patients who are likely to be cured with standard chemotherapy from
      those patients with poorer prognosis who require alternative treatment.

PMID- 11342338
TI  - High prevelance of chronic magnesium deficiency in T cell lymphoblastic leukemia
      and chronic zinc deficiency in children with acute lymphoblastic leukemia and
      malignant lymphoma.
AB  - Magnesium and zinc are the elements having essential roles in regulation of cell
      growth, division and differentiation. There have been some studies in the
      literature suggesting an association between the deficiency of these elements and
      the development of malignant disorders. In this study hair and serum zinc and
      magnesium levels were investigated in children with acute lymphoblastic leukemia
      (ALL) and malignant lymphoma (ML) at the time of initial diagnosis. Ten children
      with T-cell ALL, 10 children with B-precursor ALL, 5 children with Burkitt's
      Lymphoma (BL), 11 children with Hodgkin's lymphoma (HL), 10 children with non
      Burkitt non-Hodgkin's lymphoma (NBNHL) and 12 age and sex matched healthy
      children as a control group were included in the study. Mean hair magnesium
      levels in all of the groups of the patients were lower than the levels in the
      control group but the difference was statistically significant only in the
      children with T cell ALL comparable to the controls (28.9+/-3.9 microg/g and
      87.6+/-18.5 microg/g respectiveley, p<0,05). Mean serum magnesium levels in all
      the cohorts were not significantly different than those in controls (p>0.05 in
      each comparison). Mean hair zinc levels in the patients with T-cell, B-precursor
      ALL, BL, HL, NBNHL were 103.4+/-14.6 microg/g, 100.9+/-7.8 microg/g, 91.1+/-19
      microg/g, 72.5+/-9.1 microg/g, 103.2+/-12.2 microg/g respectively. Each of these
      levels were significantly lower than the mean hair zinc levels of the control
      group (141.2+/-9.6 microg/g, p<0.05 in each comparison). Although mean serum zinc
      levels in all of the groups were also decreased, the differences were
      statistically significant only in the groups with B-precursor ALL, HL and NBNHL
      (75.9+/-5.29 microg/dl, 68.6+/-7.3 microg/dl, 85.7+/-5.5 microg/dl respectively)
      when compared with controls (105.1+/-9.9 microg/dl, p<0.05 in each comparison).
      Hair magnesium and zinc levels showed a positive correlation with each other in
      all the groups (r congruent with 0.5). No significant difference was found in the
      mean hair/serum magnesium and zinc levels between malnourished and
      nonmalnourished patients. In conclusion, regarding the results of our study and
      previous data in the literature chronic magnesium and zinc deficiency seems to be
      associated with the development of ALL and malignant lymphoma in a group of
      patients.

PMID- 11342339
TI  - Epstein-Barr virus-latent membrane protein 1 expression has a favorable influence
      in the outcome of patients with Hodgkin's Disease treated with chemotherapy.
AB  - The effect of molecular factors in the outcome of Hodgkin's Disease (HD) is being
      currently studied. In a previous series of HD, including patients treated only
      with radiotherapy and patients treated with chemotherapy (with or without
      radiotherapy), we found that a high proliferation index had an adverse influence
      in overall survival (OS) and in the achievement of a complete remission (CR).
      Loss of Rb expression also had an adverse prognostic influence in achievement of
      CR. On the other hand LMP1-EBV expression had a favorable influence for OS. The
      expression of other molecular factors, p53, bcl2 and CD15 did not show prognostic
      influence. In the present paper we have studied the effect of these molecular
      variables in 110 patients, of the previous series who had been treated with
      chemotherapy. A retrospective study was performed in these 110 patients with HD
      treated with chemotherapy (ABVD or variants, 62%, or regimes not containing
      adriamycin, 38%) with or without adjutant radiotherapy, collected at the 11
      centers belonging to the Spanish Collaborative Group for the Study of Hodgkin's
      Disease. The prognostic value of clinical variables and the expression of p53,
      bcl2, CD15, Rb, LMP 1-EBV and proliferative fraction demonstrated with sensitive
      immunohistochemical methods were studied. Cox's multivariate analysis was
      performed to assess their influence in failure-free survival (FFS) and OS. A
      multivariate logistic regression analysis was performed for studying the effect
      of the variables in the achievement of a CR. Of the clinical variables, only
      advanced stage (III/IV) had a significant independent adverse influence in FFS,
      in OS and in the achievement of CR and advanced age in OS. Of the molecular
      variables, LMP1-EBV had an independent and strong favorable influence in FFS, in
      OS and in the achievement of CR. Rb expression had a modest favorable influence
      in CR. The rest of the molecular variables had no independent influence on the
      outcome of the disease. In conclusion these results confirm the favorable
      prognostic value of LMP1-EBV expression in the subset of patients with HD treated
      with chemotherapy.

PMID- 11342340
TI  - Increased cytotoxicity against B-chronic lymphocytic leukemia by cellular
      manipulations: potentials for therapeutic use.
AB  - B-cell chronic lymphocytic leukemia (CLL) is characterized by profound immune
      dysfunction and a marked resistance to apoptosis. Understanding the cellular
      biology of immune effector cells from CLL patients as well as leukemic target
      cells is essential to developing immune mediated therapeutic strategies for CLL.
      In this study, an immortal CLL cell line called WSU-CLL has been used to study
      the characteristics of B-cell CLL as a tumor target for natural killer (NK),
      activated natural killer, and lymphokine activated killer (LAK) cells. The WSU
      CLL cells were significantly less (p<0.001) susceptible to NK cell mediated
      cytotoxicity compared to K562, a standard tumor target cell line. In vitro
      activation of effector cells with either short term, low dose IL-2 or long term,
      high dose IL-2 significantly increased the susceptibility of CLL cells for cell
      mediated killing. The addition of CD1a+/CD3-/CD4+/CD80+/CD83+ dendritic cells
      derived from human umbilical cord blood increased the cytotoxicity of LAK cells
      against WSU-CLL. There is an increased expression of Bcl-2 and decreased
      expression of Fas on WSU-CLL cells as determined by RT-PCR techniques indicating
      possible roles for these genes in exerting resistance to immune cell mediated
      lysis. When Bcl-2 expression was downregulated in WSU-CLL cells using gene
      specific antisense oligonucleotides, the susceptibility of WSU-CLL cells to the
      cytotoxicity of chemotherapeutic agent Fludarabine was increased. Thus, our
      results suggest that in vitro activation with cytokines, addition of accessory
      cell populations such as dendritic cells and/or manipulation of key gene
      expression i.e. down regulation of Bcl-2 might be potential strategies to
      increase the antitumor cytotoxicity against CLL cells.

PMID- 11342341
TI  - Mitoxantrone, etoposide, carboplatinum and ara-C combination therapy (MECA) in
      refractory and relapsed acute leukemia.
AB  - The present study was undertaken to assess the feasibility, toxicity and
      antileukemic activity of sequential chemotherapy including mitoxantrone,
      etoposide, carboplatin and intermediate-dose cytarabine in adult patients with
      refractory and relapsed acute myelogenous (AML) or lymphoid (ALL) leukemia. Fifty
      one patients with poor-risk AML and ALL received 64 courses of MECA therapy. The
      overall response in the entire group was 51% (43% complete remission). The stage
      of the disease (relapsed or primarily refractory) and the age of the patients did
      not strongly affect the response rate. MECA therapy was more effective in ALL
      than in AML, and in those patients who presented at salvage treatment with a bone
      marrow infiltration lower than 25% blasts. Hematological and extra-hematological
      toxicities were tolerable and there were 6 deaths related to the treatment (11%).
      The incidence of documented infectious episodes was 71%. MECA therapy is a safe
      treatment and has a high antileukemic activity in relapsed and primarily
      refractory AML or ALL.

PMID- 11342342
TI  - Relationship of the CD22 immunotoxin dose and the tumour establishment in a SCID
      mice model.
AB  - Immunotoxins (ITs) may be very potent to erradicate tumour growth in vivo. We
      investigated the influence of the IT-dose, in relation to the establishment of
      the tumour, on the anti-tumour activity of CD22-recombinant (rec) ricin A for a
      disseminated tumour (Ramos) in SCID mice. Furthermore, the enhancement of the IT
      cytotoxicity in vivo by chloroquine was assessed. CD22-rec ricin A appeared to be
      highly effective. Paralysis of the hind legs was significantly delayed by a very
      low IT-dose of 2 microg administered intravenously (i.v.) 7 days after i.v.
      inoculation of the tumour cells. Even a dose of 30 microg administered 21 days
      after inoculation of the target cells significantly delayed the onset of
      paralysis up to 8 days compared with the median paralysis time (MPT) of the
      control group. The efficacy of treatment was obviously influenced by the
      establishment of the tumour, the tumour load and localisation. The anti-tumour
      activity of 10 and 30 microg IT diminished when the IT was administered after
      increasing the time lag following inoculation of tumour cells. Delaying IT
      administration resulted in growth of solid tumours. This implies that cells
      migrate to sanctuaries protected from the IT indicating that the anti-tumour
      activity was influenced by the accessibility of the IT to the target cells. The
      in vivo anti-tumour activity of CD22-rec ricin A could not be enhanced by
      simultaneously administered chloroquine, despite the continuous infusion with an
      intraperitoneally (i.p.) implanted mini-osmotic pump. Ex vivo experiments
      revealed that the maximally tolerated serum concentration (3.9 microM) was too
      low to be effective. In conclusion, CD22-rec ricin A is highly effective for in
      vivo treatment of B-cell malignancies, in particular if treatment is started when
      the tumour load is low and before migration takes place to poorly accessible
      sanctuaries.

PMID- 11342343
TI  - Bcl-2 in cell-cycle regulation of hematopoietic cells by transforming growth
      factor-beta1.
AB  - We reported that several growth factors regulate the doubling time of
      hematopoietic progenitor cells by modulating the time required to pass through
      the G1 phase. As recent studies revealed the link between cell death and cell
      cycle progression, we asked if cell death regulators such as Bcl-2 play a role in
      regulating the cell-cycle of hematopoietic cells by growth factors. Among growth
      factors, transforming growth factor-beta1 (TGF-beta1), a negative regulator of
      hematopoiesis, was chosen. When a large number of cells was required for
      analysis, we used IL-3-dependent Ba/F3 cells instead of primary hematopoietic
      progenitor cells because the response of Ba/F3 cells to TGF-beta1 was similar to
      that of primary hematopoietic progenitor cells. TGF-beta1 decelerated the cell
      cycling of hematopoietic cells by inducing a delay in G1 to S phase transition,
      an event associated with increase in the level of Bcl-2 as well as p27, a
      cyclin/cyclin-dependent kinase inhibitor. In experiments using Ba/F3 cells with
      the potential to produce Bcl-2 in an inducible manner, Bcl-2 apparently functions
      upstream of p27. The effects of TGF-beta1 on Bcl-2 and p27 expression as well as
      cell growth were abrogated by c-kit ligand. These findings suggest that Bcl-2
      plays a crucial role in regulating the cell-cycle of hematopoietic progenitor
      cells.

PMID- 11342344
TI  - Normal frequencies of the C677T genotypes on the methylenetetrahydrofolate
      reductase (MTHFR) gene among lymphoproliferative disorders but not in multiple
      myeloma.
AB  - The folate availability seems to be critical for the DNA integrity since it is
      required for the transfer of methyl groups in the biosynthesis of thymidilate.
      Although the excessive incorporation of uracils to the DNA can be efficiently
      removed, this mechanism of reparation produces many double-strand breaks from two
      opposing nicks. Several chromosomal abnormalities (mainly translocations and
      deletions perhaps not well understood) are involved in the origin of
      lymphoproliferative disorders. The TT homozygosity at nucleotide 677 in the gene
      of methylene tetrahydrofolatereductase (MTHFR), a key enzyme in folate
      metabolism, was recently linked to a significant protection against colon
      carcinoma and acute lymphoblastic leukaemia in adults. We analysed the genotype
      frequencies of C677T-MTHFR in a group of 143 patients with lymphoproliferative
      disorders (REAL classification) and 200 controls. Overally, the frequencies of
      the polymorphic allele were similar (35.3% and 32.0% respectively)(P=0.6). We did
      not find differences between patients and controls except for
      myeloma/plasmacytoma group (n=26) which showed a CC genotype less than expected
      (19% vs 46%) (p=0.01) with a frequency ratio of 0.28 (0.10-0.77). Even among the
      IgG myeloma cases only one patient showed a common genotype (CC) (1/15, 7%)
      (P=0.003). If these preliminary data are validated with prospective studies, the
      677C allele of MTHFR gene could be confirmed as an effective multiple myeloma
      protective factor (specially for the IgG cases).

PMID- 11342345
TI  - In vitro hematopoiesis in patients with malignant lymphoma during active disease
      and at complete clinical remission after chemotherapy.
AB  - Malignant lymphomas are neoplastic diseases of lymphoid cells, which usually
      originate in the lymph nodes. During the last two decades, significant progress
      has been made in the characterization of chromosomal and molecular alterations in
      these malignancies. To date, however, the composition and function of the
      hematopoietic system in this group of hematological disorders is still not fully
      understood. In the present study, we have determined the progenitor cell content
      in 10 patients with diffuse large-cell lymphoma (DLCL) and characterized the
      proliferation of these cells in long-term marrow cultures. We have also addressed
      some issues regarding the composition and function of the hematopoietic
      microenvironment in this malignancy. All the patients included in this study
      showed normal hematological parameters in peripheral blood, both before and after
      chemotherapy, however, significant hematopoietic alterations were consistently
      observed. As compared to normal subjects, lymphoma patients showed a 35%
      reduction in progenitor cell numbers, including myeloid, erythroid and
      multipotent progenitors. The in vitro proliferation of these cells was also
      deficient, since their levels in long-term marrow cultures were significantly
      lower than those observed in normal bone marrow cultures. Fibroblastic
      progenitors were reduced by >50% and this correlated with a deficient adherent
      cell layer development in culture. A reduction was also seen in the levels in
      culture supernatant of the stimulatory cytokines Stem Cell Factor and Interleukin
      6. Interestingly, all the hematopoietic alterations mentioned above were still
      present in patients at complete clinical remission after chemotherapy. Thus, in
      the present study we have demonstrated significant in vitro deficiencies in the
      composition and function of the hematopoietic system in patients with diffuse
      large-cell lymphoma, both during active disease and at the time of complete
      clinical remission.

PMID- 11342346
TI  - CD5+ true SLL/CLL with plasmacytic differentiation and an unusual 1p36
      translocation: case report and review of the literature.
AB  - Lymphoplasmacytic lymphoma (LPL) and small lymphocytic lymphoma/chronic
      lymphocytic leukemia (SLL/CLL)are distinct clinicopathologic entities. Although
      some cases of SLL/CLL may show plasmacytic differentiation and be associated with
      monoclonal immunoglobulin in serum, such cases appear to be very rare, and if
      plasma cell differentiation were marked, differentiation of SLL/CLL from LPL
      could be difficult. We report a rare case of true CD5-positive small lymphocytic
      lymphoma/chronic lymphocytic leukemia with unequivocal plasmacytic
      differentiation. This case also showed an abnormality of chromosome 1p36 not
      previously described in small lymphocytic lymphoma/chronic lymphocytic leukemia.

PMID- 11342348
TI  - An infant with precursor natural killer (NK) cell leukemia successfully treated
      with an unrelated cord blood transplantation.
AB  - Here we report a case with precursor natural killer (NK) cell leukemia
      successfully treated with an unrelated cord blood transplantation. A 7-month-old
      Japanese boy was diagnosed to have NK cell leukemia based on the existence of
      abnormal cells in the bone marrow with the phenotype of CD3(-) /CD4(+) /CD7(-)
      /CD8(-) /CD16(-) /CD33(+) /CD34(-) /CD56(+) /HLA-DR(+) /NKB1(+) / CD94(+). The
      leukemic cells showed few azurophilic granules in the cytoplasm and weak
      cytotoxic activity. Although he presented with a huge mass occupying the
      bilateral paranasal sinuses and hepatosplenomegaly, he achieved complete
      remission by the conventional chemotherapeutic regimen for acute myelogenous
      leukemia, followed by an unrelated cord blood transplantation. He has remained in
      complete remission for 14 months posttransplant. To our knowledge, this is the
      youngest reported case with precursor NK cell leukemia; cord blood
      transplantation may thus be the treatment of choice for this disease.

PMID- 11342347
TI  - CD7 and CD56-positive primary effusion lymphoma in a human immunodeficiency virus
      negative host.
AB  - Primary effusion lymphoma is an entity with distinctive features. The majority of
      cases are diagnosed in patients infected with human immunodeficiency virus. We
      report a case of pleural-based primary effusion lymphoma in an elderly patient
      negative for human immunodeficiency virus. By flow cytometry, lymphoma cells
      expressed CD7, CD38, CD45, CD56, HLA-DR, and kappa surface light chains. A
      monoclonal rearrangement of the immunoglobulin heavy chain and the presence of
      human herpesvirus 8 genome were detected. Our case lacked CD30 or CD138 with
      expression of surface light chains. There was strong expression of CD7 and CD56.
      These findings are unusual or unique in primary effusion lymphoma. Our report
      suggests that aberrant expression of T cell and natural killer cell markers can
      be seen in primary effusion lymphoma.

PMID- 11342349
TI  - Acute pancreatitis associated with interferon alpha therapy for chronic
      myelogenous leukemia.
AB  - Acute pancreatitis related to interferon alpha therapy is very rare. We report
      two patients with chronic myelogenous leukemia (CML) who developed acute
      pancreatitis following treatment with interferon alpha. A review of the
      literature on the association of pancreatitis and interferon alpha is provided.
      Possible pathophysiologic mechanisms are also discussed.

PMID- 11342350
TI  - Acute myeloid leukemia with inv(8)(p11q13).
AB  - A patient with acute monoblastic leukemia (AML M5a) and the pericentric inversion
      inv(8)(p11q13) as well as additional chromosome abnormalities in her bone marrow
      cells is described. This is the fourth known case of inv(8)(p11q13)-positive
      acute leukemia, and the second such case in which gain of 1q material occurred
      during clonal evolution. All patients with acute leukemia and inv(8)(p11q13) have
      been females, most have been young, and there has been a tendency for the disease
      to run an aggressive course. Both hematologically and cytogenetically, therefore,
      inv(8)(p11q13)-positive leukemia may be viewed as a variant of AML with
      t(8;16)(p11;p13). This similarity is also apparent at the molecular genetic
      level, in-as-much as the MOZ gene in 8p11 is rearranged in both the translocation
      and the inversion; in t(8;16)-positive leukemia, a MOZ-CBP chimeric gene is
      generated, whereas inv(8) has been shown to generate a MOZ-TIF2 fusion gene.
      Southern blot analysis of the present case after MOZ0.8 hybridization of Bam HI
      digested DNA gave an 11 kb aberrant band in addition to the germline band,
      corresponding to a breakpoint immediately upstream of the 4 kb long MOZ exon that
      begins at position 3746. Also previously investigated inv(8)-positive leukemias
      have shown breaks in this intron indicating that it contains sequence motifs
      predisposing to illegitimate recombination.

PMID- 11342351
TI  - Guillain-Barre syndrome following 2-chlorodeoxyadenosine treatment for Hairy Cell
      Leukemia.
AB  - A 68-year-old man, with Hairy Cell Leukemia developed a Guillain-Barre syndrome
      (G-B), 32 days after a single course of 2-Chlorodeoxyadenosine (CDA) at 0,14
      mg/k/d, for five days in a two-hour-i.v. infusion and following a febrile
      neutropenia episode. In order to clarify whether this G-B case was related to an
      infection or to CDA neurotoxicity, we screened for infection-related autoimmune G
      B and for antibodies (abs.) against gangliosides of peripheral nerves. Blood and
      urinary cultures were negative as well as serum anti-virus abs. However, serum
      anti-ganglioside abs. were positive for anti-asialo GM1 and anti-Gd1b. This
      latter finding was consistent with an autoimmune mechanism, not described until
      now as CDA neurotoxicity. In the present case, we do not have enough evidence to
      link CDA administration to the G-B syndrome. We think that it is necessary to
      exclude other causes of neurotoxicity before considering CDA adverse effect.

PMID- 11342352
TI  - Myelofibrosis in systemic lupus erythematosus.
AB  - In this study we present a case of coexisting systemic lupus erythematosus (SLE)
      and myelofibrosis. Literature review supports the fact that the two diseases
      rarely occur together in the same patient. The young female patient studied was
      admitted with pancytopenia and a clinical picture which met the criteria of SLE.
      Histological examination of the bone marrow biopsy revealed severe myelofibrosis
      with hypocellularity of the myeloid cell lines. Treatment with immunosuppressive
      and colony stimulating factor led to slow but complete regeneration of the bone
      marrow and subsequently to an improved haematological status, and the patient was
      spared bone marrow transplantation.

PMID- 11342353
TI  - Current status of retroviral vector mediated gene transfer into human
      hematopoietic stem cells.
AB  - Genetic modification of hematopoietic stem cells (HSCs) has been proposed as a
      treatment strategy for a variety of hematologic diseases, tracking marked cells
      or conferring resistance to chemotherapeutic agents. Despite early enthusiasm,
      the results of clinical studies involving gene transfer into HSCs have not
      resulted in therapeutic benefits for the vast majority of treated patients. This
      review describes the limitations and advances that have been made in the areas of
      gene transfer vectors, identification of the appropriate HSCs to target for
      genetic modifications and the methods used to perform gene transfer.

PMID- 11342354
TI  - Bone marrow cell graft engineering: from bench to bedside.
AB  - Bone marrow transplantation (BMT) has the potential to treat hemoglobinopathies
      (sickle cell and thalassemia) autoimmunity (diabetes, lupus, multiple sclerosis,
      rheumatoid arthritis, Crohn's colitis) and enzyme deficiency states. Graft versus
      host disease (GVHD) is a major complication and limitation to the therapeutic
      application of BMT. There have been many clinical trials and experimental animal
      models that have attempted to control GVHD through the engineering of the donor
      bone marrow cells (BMC). Historically, several methods have demonstrated
      effectiveness in controlling GVHD; however they were also associated with a
      marked increase in the rate of graft failure. Highly purified hematopoietic stem
      cells (HSC) engraft quite readily in genetically-matched recipients while they do
      not engraft as easily in MHC-disparate recipients. The numbers of HSC must be
      increased 100-200 fold in order to overcome the allogeneic barrier. We were the
      first to phenotypically and to functionally characterize a novel cell in the bone
      marrow that enables engraftment of highly purified HSC in allogeneic recipients.
      The discovery of graft facilitating cell populations has resulted in the
      restoration of the engraftment-potential of purified HSC between genetically
      disparate individuals. The addition of facilitating cells (FC) to T cell-depleted
      BMC grafts results in allogeneic engraftment without GVHD or graft failure. New
      strategies of BMC engineering that retain FC and HSC but avoid GVHD have allowed
      successful engraftment in mismatched and older recipients. These techniques have
      expanded the therapeutic potential of BMT to virtually every candidate as well as
      to non-malignant diseases in which the morbidity associated with conventional BMT
      could not be accepted. This article reviews the transition of the FC technology
      from bench to bedside and discuss the potentially broad-reaching applications of
      BMT and mixed chimerism.

PMID- 11342355
TI  - Telomerase activity and clinical progression in chronic lymphoproliferative
      disorders of B-cell lineage.
AB  - The activation of telomerase, which specifically occurs in neoplastic cells to
      avoid telomere attrition at each cell division, is a necessary event in
      tumorigenesis. The evidence that telomerase is also present in normal B cells at
      different levels according to their differentiation and activation state makes
      the study of telomerase activity in B cell tumors particularly interesting. This
      review summarizes data concerning telomerase activity in chronic
      lymphoproliferative disorders of B-cell lineage (B-CLD), making suggestions
      regarding B-cell development and B-cell tumor histogenesis. The role of
      telomerase activity as a potential prognostic marker, as well as a target of new
      antineoplastic strategies is discussed.

PMID- 11342356
TI  - Genetic alterations in primary mediastinal B-cell lymphoma: an update.
AB  - Primary mediastinal B-cell lymphoma (PMBL) is a distinct clinical entity among
      non-Hodgkin's lymphoma. The malignancy has received little attention from a
      standpoint of basic research due in part to its rarity. However, based on recent
      studies consistent trends are beginning to emerge regarding the molecular and
      chromosomal alterations commonly observed in this disease. By both CGH and AP
      PCR, genetic gains involving chromosomes 2, 5, 7, 9p, 12, and Xq are among the
      most frequently observed events. From a molecular standpoint, alterations in the
      c-myc, p16(INK4) and p53 genes have been observed in up to 30% of cases. This
      information along with the well-established histological, immunological, and
      clinical features should convince the few remaining disbelievers that PMBL is a
      distinct pathological entity among non-Hodgkin's lymphomas.

PMID- 11342357
TI  - Autoimmune lymphoproliferative syndrome type III: an indefinite disorder.
AB  - Autoimmune Lymphoproliferative Syndrome (ALPS) is a childhood disorder
      characterized by chronic nonmalignant lymphoproliferation and autoimmunity.
      Although the pathogenesis is not fully understood, deficient Fas mediated
      apoptosis appears to be an important factor. This deficiency can be caused by a
      mutation of the APT1 gene (ALPS type Ia), of the FasL gene (ALPS type Ib), or of
      the Caspase-10 gene (ALPS type II). In one sub population of patients, no
      mutations have been identified as yet (ALPS type III). According to published
      data, the latter group is much smaller than the group of patients with ALPS type
      Ia. However, because of the variability of the clinical presentation and the
      absence of a known genetic defect, this disease is difficult to diagnose, the
      more so as few data have been reported on these patients. Thus, ALPS type III
      could be more common than believed until now. In this review we provide evidence
      for this hypothesis.

PMID- 11342358
TI  - Lowering the prophylactic platelet transfusion threshold: a prospective analysis.
AB  - The 20 x 10(9) /L threshold for prophylactic platelet transfusion may be
      unnecessarily high. Few prospective studies, however, in which other trigger
      values were tested have been published. In this study all hospitalized,
      thrombocytopenic adult hematology-oncology patients in our institution were
      prospectively evaluated daily for hemorrhage and platelet transfusion during a
      one year period; no patients were excluded for bleeding or infectious problems.
      By design, during the initial six-months (baseline period), the prophylactic
      platelet transfusion trigger was 20 x 10(9) /L; for the second six-months (study
      period) this threshold was changed to 10 x 10(9) /L. Patients studied during the
      two periods did not differ significantly in age, gender, diagnosis, blood or
      marrow transplant status, and duration of neutropenia. Compliance with the
      thresholds was 95.6% (baseline period) and 93.5% (study period). For patients
      with platelet counts under 20 x 10(9) /L, the mean use of platelet transfusions
      per patient per day was significantly lower in the study period (4.47) than in
      the baseline period (6.48; p<0.001). Both mean prophylactic (1.54/patient-day)
      and therapeutic (2.93/patient-day) platelet transfusions were reduced in the
      study period compared with the baseline period (2.26 and 4.22/patient-day,
      respectively). Hemorrhage was slightly reduced in the study period compared with
      the baseline period: major hemorrhage, 15.2% vs. 18.4% (p=0.014); minor
      hemorrhage, 63.6% vs. 70.1% (p<0.001). Thus, hemorrhage was not increased with
      the lower trigger level. A 10 x 10(9) /L prophylactic platelet transfusion
      threshold value is safe and effective.

PMID- 11342360
TI  - Bone marrow transplantation in hemophagocytic lymphohistiocytosis.
AB  - Two important syndromes of hemophagocytic lymphohistiocytosis (HLH) have to be
      considered in infants and young children with recurrent fever, organomegaly and
      cytopenias. Familial hemophagocytic lymphohistiocytosis (FHLH) is a genetically
      heterogeneous autosomal recessive disease with histiocytic and lymphocytic
      infiltrations in multiple organs and is currently curable only by bone marrow
      transplantation (BMT). Secondary HLH most commonly results from viral infections
      and some patients may be cured by treating the causative organism, others will
      need chemotherapy and immunosuppression. Since infections can also trigger
      disease episodes in FHLH, making the correct diagnosis can prove difficult. The
      published experience of BMT in HLH is reviewed. Taken together, cure of the
      majority of patients with HLH by matched related BMT, unrelated or haploidentical
      BMT is possible. Incomplete resolution of disease activity does not necessarily
      impede a successful outcome. Central nervous system involvement will eventually
      develop in many HLH patients and may cause considerable morbidity. Appropriate
      early treatment and a timely BMT will hopefully decrease mortality rates and
      improve neurodevelopmental outcome in this disease.

PMID- 11342359
TI  - A phase II multicenter study of CAMPATH-1H antibody in previously treated
      patients with nonbulky non-Hodgkin's lymphoma.
AB  - CAMPATH-1H is a humanized antilymphocyte monoclonal antibody (mAb) directed
      against the CD52 antigen expressed on normal and malignant lymphocytes. We report
      the results of a multicenter phase II trial using intravenous CAMPATH-1H in
      previously treated patients with nonbulky non-Hodgkin's lymphoma (NHL) or minimal
      residual NHL. Sixteen previously treated patients with nonbulky NHL and two
      patients with minimal residual NHL, were treated with CAMPATH-1H. Changes in
      peripheral blood lymphocyte subsets were analyzed by multiparameter flow
      cytometric techniques in eleven patients. The 18 patients enrolled in the studies
      received CAMPATH-1H for a median duration of 6 weeks (range, 3 to 14 weeks), and
      a median cumulative dose of 470 mg (range, 180 to 1185 mg). Two of the sixteen
      patients with nonbulky NHL achieved a complete response (CR) and one patient
      achieved a partial response (PR). One of the two patients with minimal residual
      NHL achieved a molecular CR. Infusional complications were seen with the majority
      of patients but were more common with initial infusions. Significant hematologic
      toxicity was also observed with grade (3/4) thrombocytopenia (n=10), grade (3/4)
      neutropenia (n=4) and grade 3 anemia (n=3). Due to excessive infectious
      complications observed with the patients enrolled, the trials were terminated
      early. Anti-tumor activity was demonstrated in a small subset of previously
      treated low-grade lymphoma patients with nonbulky or minimal residual disease.
      Future studies evaluating the effect of different drug schedules, modes of mAb
      administration, and concurrent use of prophylactic
      antibiotics/antiviral/antifungal agents to optimize anti-tumor activity and limit
      infectious toxicities are planned.

PMID- 11342362
TI  - Changing incidence and survival in patients with aids-related non-Hodgkin's
      lymphomas in the era of highly active antiretroviral therapy (HAART).
AB  - To determine role of highly active antiretroviral therapy (HAART) and additional
      factors in incidence and outcome of patients with AIDS-related non-Hodgkin's
      lymphomas (NHL) we retrospectively analyzed 257 cases of AIDS-related NHL (24 low
      grade, 168 high-grade B-cell, 6 high-grade T-cell, and 59 primary CNS lymphomas
      (PCNSL) among 2004 patients with HIV-infection treated at the University Hospital
      of Frankfurt, Germany from January 1983 to May 1999. Data were evaluated by
      univariate and multivariate analyses, using overall survival as end point.
      Patients received CHOP-like therapy as standard treatment. Until May 1999
      incidence of all diagnosed cases of NHL was decreasing (1991-94: 14.2% versus
      1995-5/99: 12.8%). Mainly, the incidence of low-grade NHL and PCNSL clearly
      decreased whereas the incidence of high-grade B-cell NHL increased compared to
      all diagnosed cases of NHL (1983-86: 53.3% versus 1995-5/99: 78.6%). One-year
      survival probability of all screened patients with AIDS related NHL was 54%,
      while 5-year survival rate remained 5%. We found age <25 years, development of
      NHL in the years before 1990, IVDU, CD4 counts <150/microl, PCNSL as well as NHL
      as the AIDS index disease, to be highly significant independent predictors of
      poor survival, including increased hazard ratios. In the era of HAART incidence
      of NHL is decreasing, mainly the incidence of low-grade NHL and PCNSL. Overall
      survival of patients has been prolonged with HAART. This development is mainly
      due to improvement of antiretroviral therapy, rather than to any fundamental
      changes in the chemotherapeutic treatment of NHL. Therefore, new treatment
      approaches for AIDS-related NHL should focus on more efficient antiretroviral
      therapy in association with combination chemotherapy.

PMID- 11342361
TI  - Is total body irradiation a necessary component of preparative therapy for
      autologous transplantation in non-Hodgkin's lymphoma.
AB  - Between September 1986 and June 1998, 157 patients with low grade, intermediate
      grade, or high grade lymphoma underwent autologous transplantation at a single
      institution. Two preparative regimens were used: cyclophosphamide, etoposide,
      total body irradiation (CY-VP-TBI) (N=110) and cyclophosphamide, BCNU, etoposide
      (CBV) (N=47). The two groups were not significantly different with respect to
      source of stem cells, gender, stage at presentation, incidence of prior bone
      marrow involvement, sensitivity to salvage therapy, or histologic grade of
      lymphoma. The CBV group was significantly older, 49% of patients over age 50, as
      compared to 26% of patients over age 50 for the CY-VP-TBI group. Response rates
      and the incidence of fatal toxicity were similar for the two groups. Five year
      actuarial survival was 31% +/- 9% for CBV and 38% +/- 5% for CY-VP-TBI, p =.85.
      In a multivariate analysis, in which preparative regimen, age, histologic grade
      of lymphoma, and sensitivity to salvage therapy were the independent variables,
      TBI was not significantly associated with survival, and the direction of the
      trend was for TBI to be less effective than CBV. TBI does not appear to be an
      essential component of preparative therapy for autologous transplantation in
      patients with lymphoma.

PMID- 11342363
TI  - Cytarabine added to interferon improves the cost-effectiveness of initial therapy
      for patients with early chronic phase chronic myelogenous leukemia.
AB  - The French Chronic Myeloid Leukemia Study Group prospective randomized study
      results indicate that the addition of cytarabine to alpha interferon (IFN-alpha)
      increases the rate of major cytogenetic response and prolongs survival in
      patients with early chronic phase chronic myelogenous leukemia (CML). The French
      group study design permitted a single crossover to include or discontinue
      cytarabine or interferon. Endpoints were overall survival, complete hematologic
      remission (CHR) at six months, and major cytogenetic response at 12 months. We
      modified a published Markov model that compared IFN-alpha alone to IFN-alpha plus
      cytarabine and included the possibility of crossover as in the French study. The
      model permits allogeneic and autologous stem cell transplantation (SCT), and
      follows cytogenetic response and acceleration of CML through death. Treatment
      response, toxicity, and survival are drawn from the French Chronic Myeloid
      Leukemia Study Group population of 810 patients on an intention-to-treat model.
      Survivals are extended to 62 months based on currently available follow-up. Costs
      from a United States oncology specialty institution, and state utilities from
      previous research and a quality-adjusted Time Without Symptoms or Toxicity
      analysis of the subject study were discounted at 3% per annum. At the median
      cohort age of 50, cytarabine offers 21 months of added median survival to IFN
      alpha, which itself is superior to conventional chemotherapy by 21 months. Cost
      effectiveness estimates for cytarabine added to IFN-alpha range from $7,000 per
      quality-adjusted life year (QALY) to $35,000 per QALY, under all plausible
      assumptions superior to IFN-alpha alone. The model is sensitive to the quality of
      life on therapy, as well as to remission rate with additive cytarabine, although
      the cost-effectiveness calculations are robust over the entire range of clinical
      assumptions. Based on data from the French study, cytarabine added to IFN-alpha
      substantially improves the cost-effectiveness of initial therapy for early
      chronic phase CML.

PMID- 11342365
TI  - Fludarabine in alkylator-resistant follicular non-Hodgkin's lymphoma.
AB  - Follicular small cell and follicular mixed small and large cell lymphoma (FL) are
      incurable with conventional chemotherapy, and generally follow a relapsing
      course, eventually becoming resistant to first-line therapy with alkylating
      agents. Fludarabine is a novel chemotherapeutic agent that is effective in FL,
      but its role in alkylator-resistant disease remains unclear. We conducted a
      retrospective review of all patients with alkylator-resistant FL treated with
      fludarabine. Patients were identified from pharmacy records and included if they
      fulfilled criteria for alkylator-resistant FL. Resistance was defined as failure
      to achieve a partial response, progression while on therapy, or relapse within
      six months of completing therapy. Seventeen patients met the criteria of
      alkylator-resistant FL and were included in the analysis. All patients received
      fludarabine 25 mg/m(2) for five days. A median of 2.5 courses of fludarabine was
      given. One patient had a complete remission and eight patients had partial
      remissions, for an overall response rate of 53%. Median progression-free survival
      was 5.4 months and median overall survival was 15.4 months for all patients. Four
      patients underwent subsequent autologous stem cell transplantation; all required
      additional salvage chemotherapy for post-fludarabine relapses. Three patients
      remain in remission more than 12 months post-transplantation. Fludarabine
      produces partial responses in patients with advanced refractory FL; however, the
      duration of the response limits its utility in alkylator-resistant disease.

PMID- 11342364
TI  - Cemp, a mitoxantrone containing combination, in the treatment of intermediate and
      high grade non-hodgkin's lymphoma: an effective and non toxic therapeutic
      alternative for adult and elderly patients.
AB  - Here we report the results of a randomised multicenter phase III clinical trial
      which assesses the therapeutic efficacy and tolerability of a chemotherapy
      protocol CEMP (cyclophosphamide, etoposide, mitoxantrone and prednisone) in adult
      and elderly patients with advanced intermediate and high-grade NHL. Between
      October 1991 and October 1995, 139 patients, aged 55 to 79 years, with diffuse
      intermediate and high-grade lymphoma, were enrolled. A considerable percentage of
      patients had clinically aggressive disease: 32.4% had systemic symptoms, 79% had
      stage III or IV disease, 33.8% had bone marrow involvement, 46% had splenic
      involvement and 42.5% had increased values of serum lactate dehydrogenate.
      Complete remission was achieved in 70 of the 139 patients (51.9%) and PR in 12
      (16.6%) with an overall response of 68.5%. The overall response survival rate at
      6 years was 39%, whereas DFS rate was 48.7% and PFS rate was 28.5%. At four years
      49% of the patients were still in CR. Dividing the patients in two groups, under
      and over 65 years of age, we obtained the same results as far as overall response
      is concerned. No toxic deaths occurred, neither cardiac, renal nor liver
      complications happened. CEMP regimen is an effective and safe protocol with good
      results in elderly people, well comparable to those achieved in younger ones.

PMID- 11342366
TI  - Hyperhomocysteinemia in myelodysplastic syndromes: specific association with
      autoimmunity and cardiovascular disease.
AB  - Hyperhomocysteinemia (HH) has been associated with cardiovascular and autoimmune
      diseases and oxidative cell damage. Myelodysplastic syndromes (MDS) are
      associated with autoimmunity (AI) and increased oxidative stress. We tested the
      association of HH and oxidative stress in 33 MDS patients, by measuring plasma
      homocysteine and malondialdehyde (MDA). HH was found in 42% of cases, (4/5) cases
      with associated cardiovascular events (CVE)(80%), and 9/15 cases with associated
      AI (60%). Thus in MDS, HH was significantly associated with AI/CVE (chi(2) :
      p=0.0011), and this association seems to be specific, as demonstrated by the
      comparison of MDS presenting AI/CVE with the ischemic cardiopathy/rheumatoid
      arthritis control group (13/20, 65% vs 19/69, 27%; chi(2) : p=0.0021). The levels
      of MDA indicated increased oxidative stress. Our data may suggest that in a
      subset of MDS, HH may simultaneously contribute to bone marrow myelodysplasia,
      CVE and AI pathogenesis, possibly through oxidative cell damage.

PMID- 11342367
TI  - Hodgkin's disease involving Waldeyer's ring: a study of four cases.
AB  - We report four cases of Hodgkin's disease who presented with involvement of
      Waldeyer's ring. Their clinical, morphological and immunohistochemical features
      are discussed. The patients were immuno-competent, were between 17 and 65 years
      of age and presented with symptoms related to swelling in the nasopharynx or
      oropharynx and cervical lymphadenopathy. The nasopharyngeal biopsy and the
      cervical lymph node in all four cases showed features of classical Hodgkin's
      disease. The Reed Sternberg cells expressed CD15 and CD30, and in three cases,
      CD20 and Epstein-Barr virus--latent membrane protein -1 (EBV-LMP-1). Extranodal
      involvement by Hodgkin's disease which is not in continuity with nodal disease is
      rare in immunocompetent patients. Morphologically, such extranodal lesions,
      especially in locations like the oropharynx and nasopharynx, should be
      differentiated from EBV-associated lymphoproliferations.

PMID- 11342368
TI  - Familial persistent polyclonal B-cell lymphocytosis.
AB  - We report the occurrence of the syndrome of persistent polyclonal B-cell
      lymphocytosis in a brother and a sister. Both showed the morphological and
      immunophenotypic features of this rare disorder. In addition both had mild
      splenomegaly, increase of serum IgM and serological evidence of previous EBV
      infection. Of interest, two additional brothers had no evidence of PPBL but were
      indistinguishable in terms of HLA haplotype (HLA-DR7), smoking habits or evidence
      of EBV infection. These observations provide additional support for a genetic
      basis of the syndrome but suggest that pathogenic factors other than those known
      so far may be required for its full expression.

PMID- 11342370
TI  - Soluble Fas (APO-1/CD95) isoform in adult T-cell leukemia.
AB  - Fas (APO-1/CD95) consists mainly of 2 isoforms, membrane-anchored (mFas) and
      soluble (sFas), both of which can mediate apoptosis through the Fas-signalling
      process, not only in normal but also in leukemia T-cells. This suggests that
      aberrant expression of either mFas or sFas may affect the natural history of T
      cell neoplasms, such as adult T-cell leukemia (ATL). For studying the tumor
      biology related to Fas-mediated apoptosis, ATL cells with up-regulated Fas
      proteins and its mRNAs are convenient and useful for understanding apoptotic
      oncology as it occurs in nature. Most attention, so far, has been focused on
      mFas, and little is known about neoplasms from the viewpoint of sFas.
      Accordingly, we herein review and discuss the biological and clinical
      implications of sFas in ATL.

PMID- 11342369
TI  - In vivo effects of IL-4, IL-10, and amifostine on cytokine production in patients
      with acute myelogenous leukemia.
AB  - Both IL-4 and IL-10 have been shown in vitro to inhibit leukemia cell secretion
      of IL-1beta, GM-CSF, and TNFalpha, and increase leukemia cell release of IL-1ra.
      In this study, we have investigated the in vivo effects of IL-4, IL-10, and
      amifostine on cytokine production in patients with acute myelogenous leukemia
      (AML). Serum IL-1ra, IL-1beta, TNFalpha, GM-CSF, and SCF levels were measured in
      AML patients who received IL-4, IL-10, or amifostine. No significant changes in
      the serum levels of IL-1ra, IL-1beta, TNFalpha, GM-CSF, and SCF were found in AML
      patients who received amifostine. Both IL-4 and IL-10 were found to increase
      serum IL-1ra. This data is in accord with the in vitro studies. However, IL-4
      increased serum GM-CSF levels and IL-10 increased serum IL-1beta and TNFalpha
      levels. These in vivo effects of the two cytokines differ from their in vitro
      effects. Despite the similar effects of IL-4 and IL-10 on cytokine production by
      AML cells in vitro, different effects were observed in AML patients in vivo. IL-4
      increased serum SCF levels, whereas IL-10 decreased serum SCF levels. IL-4
      increased serum GM-CSF levels, whereas IL-10 had no effect on them. Although IL
      10 increased serum IL-1beta and TNFalpha levels, IL-4 had no effect on them.
      These findings indicate that the in vitro effects of IL-4 and IL-10 do not
      necessarily reflect their in vivo effects, and that the complex effects of the
      two cytokines on serum cytokine levels make it difficult to predict their
      therapeutic potential.

PMID- 11342371
TI  - PPP2R1B gene in chronic lymphocytic leukemias and mantle cell lymphomas.
AB  - Deletion of chromosome bands 11q22-q23 is one of the most common structural
      chromosome alterations in chronic lymphocytic leukemia (CLL) and mantle cell
      lymphoma (MCL). The PPP2R1B gene is located very close to the minimal common
      deletion region of 11q22-q23 in CLL and MCL. Recently, the PPP2R1B gene was found
      to be mutated in human lung and colon cancers. To evaluate the role of the
      PPP2R1B gene in the pathogenesis of CLL and MCL, we performed RT-PCR analysis and
      cDNA sequencing on 10 CLL RNA samples and SSCP analysis on 26 CLL and 37 MCL
      genomic DNA samples. A deletion of exon 3 was found in one CLL sample. No
      mutation was detected in the SSCP analysis. To exclude the possibility of large
      genomic deletions we performed Southern blotting analysis. One MCL sample showed
      abnormal bands. Our results do not suggest that the PPP2R1B gene has a major
      pathogenic role in CLL and MCL.

PMID- 11342372
TI  - Primary effusion lymphoma in an HIV-negative patient with no serologic evidence
      of Kaposi's sarcoma virus.
AB  - Primary effusion lymphoma (PEL) is a newly described high-grade B cell lymphoma
      which develops in association with Kaposi's sarcoma-associated herpesvirus (KSV)
      in human immunodeficiency virus (HIV)-infected individuals. We hereby describe a
      very unusual presentation of PEL that developed in the abdominal cavity of an HIV
      negative, KSV negative patient with a 1-year history of refractory ascites due to
      alcohol-related liver cirrhosis. Possible factors aiding lymphomagenesis in the
      cirrhotic state are discussed.

PMID- 11342373
TI  - Lamivudine and glycyrrhizin for treatment of chemotherapy-induced hepatitis B
      virus (HBV) hepatitis in a chronic HBV carrier with non-Hodgkin lymphoma.
AB  - We report a chronic hepatitis B virus (HBV) carrier with non-Hodgkin lymphoma
      (NHL) who developed HBV hepatitis following conventional dose chemotherapy and
      was successfully treated with lamivudine and glycyrrhizin. A 55 year-old male
      patient with primary testicular NHL (diffuse large B-cell type) relapsed. During
      the salvage chemotherapy, the patient showed elevated serum levels of
      transaminase and HBV-DNA due to HBV reactivation. Treatment with lamivudine, an
      antiviral nucleoside analog, was started at a dose of 100mg/day. Shortly after
      the treatment the HBV-DNA level was suppressed, and sustained elevation of
      transaminase levels were normalized after additional treatment with glycyrrhizin.
      This experience suggests that lamivudine combined with glycyrrhizin may be
      effective for controlling HBV replication and treating chemotherapy-induced HBV
      hepatitis in chronic HBV carriers with NHL.

PMID- 11342374
TI  - Pathologic splenic rupture as the presentation of mantle cell lymphoma.
AB  - Pathologic splenic rupture in non-Hodgkin's lymphoma (NHL) is a rare event, with
      32 cases previously reported. Initial presentation of NHL with this complication
      is even rarer. We report such a case in an 80-year-old man with mantle cell
      lymphoma (MCL). It is notable that of the previously reported cases of pathologic
      rupture, three have occurred in MCL, suggesting that patients with this uncommon
      subtype of NHL may be particularly vulnerable to pathologic splenic rupture.
      Following splenectomy the patient's disease behaved in a high-grade fashion.
      Despite an initially encouraging response, his disease ran an aggressive course
      and he succumbed within four months. This case demonstrates the presentation of
      MCL with pathologic splenic rupture, as well as the potentially highly malignant
      behaviour of the disease.

PMID- 11342376
TI  - T-large granular lymphocyte leukemia accompanied by an increase of natural killer
      cells (CD3-) and associated with ulcerative colitis and autoimmune hepatitis.
AB  - Clonal expansion of large granular lymphocyte(LGL) have been classified into T
      LGL and NK-LGL leukemia. T-LGL leukemia cells have a CD3+ phenotype and show
      clonal T-cell receptor(TCR) gene rearrangement. NK-LGL leukemia cells have a CD3-
      phenotype and no TCR gene rearrangement. We report a case of T-LGL leukemia
      accompanied by NK LGL expansions in a 65-year-old man who was observed 3 years
      earlier to have a LGL lymphocytosis in association with ulcerative colitis(UC)
      and autoimmune hepatitis (AIH). Phenotypic analysis of peripheral blood by flow
      cytometry disclosed an increase of both T-LGL(CD3+,CD56-,CD57+,and TCRalphabeta+)
      and NK-LGL (CD3-,CD16+,CD56+, and CD57+). Clonal rearrangement of the TCR beta
      gene was detected. A diagnosis of UC and AIH was made on the basis of the X-ray
      and mucosal biopsy findings of the large intestine, and on the scoring system for
      diagnosis of AIH, respectively. The disease was nonprogressive, and mesalazine
      and prednisolone were successful for treatment of UC and AIH. Previously reported
      cases of T-LGL, NK-LGL leukemia, or NK cell lymphocytosis had no association with
      UC or AIH, and there have been no reports having both T-LGL leukemia with T-cell
      receptor gene rearrangement and chronic NK cell lymphocytosis co-existing in a
      single patient.

PMID- 11342375
TI  - Hypercalcemia as the presenting feature of t-cell lymphoid blast crisis of ph
      positive chronic myeloid leukemia.
AB  - Hypercalcemia is a rare complication of chronic myeloid leukemia (CML), usually
      seen in the accelerated or blastic phases of the disease and associated with a
      poor prognosis. T-cell lymphoid phenotype is also an infrequent finding in the
      blast crisis (BC) of CML. A CML patient who had hypercalcemia as the presenting
      feature of a T-cell BC is reported. She was a 78 year-old woman who, at four
      months of CML diagnosis, developed weakness, bone pain, and mental confusion,
      with hypercalcemia being subsequently found. Although the peripheral blood and
      bone marrow were consistent with the chronic phase of CML, mediastinal
      enlargement, a soft tissue mass adjacent to the iliac bone, and multiple
      osteolytic lesions were seen. Serum levels of parathyroid hormone (PTH) and PTH
      related peptide were normal, whereas the search for a second neoplasm was
      negative. The hypercalcemia initially responded to conventional treatment, but it
      reappeared two weeks later. Coincidentally, a high proportion of blast cells of T
      cell origin at the cortical thymocyte stage were observed in the patient's
      peripheral blood and bone marrow, and she died shortly afterwards.

PMID- 11342377
TI  - Reversal of fludarabine induced testicular damage in a patient with chronic
      lymphocytic leukaemia (CLL), by suppression of pituitary-testicular axis using
      gonadotrophin releasing hormone (GnRH).
AB  - We describe a case of a 47 year old man with CLL who was treated with 7 courses
      of fludarabine with simultaneous suppression of his pituitary-testicular axis (P
      T) with Gonadotrophin releasing hormone (GnRH) and replacement treatment with
      testosterone. Despite initial gonadal damage as evident by endocrine and sperm
      studies, testicular recovery was observed 11 months post treatment. Although
      spontaneous recovery cannot be ruled out, continuous treatment with GnRH and
      testosterone may play a crucial role protecting the gonads from the cytotoxic
      effects of the chemotherapeutic agents.

PMID- 11342378
TI  - Idiopathic thrombocytopenic purpura following successful treatment of acute
      lymphoblastic leukemia.
AB  - Thrombocytopenia is common in patients with acute lymphocytic leukemia (ALL) at
      diagnosis. It is a universal side effect of dose-intensive regimens employed in
      the treatment of adult ALL. In patients with ALL who achieve remission,
      thrombocytopenia frequently indicates relapse. We report three adult patients
      successfully treated for ALL who developed thrombocytopenia and were found to
      have immune-mediated thrombocytopenia (ITP). Possible pathophysiologic mechanisms
      underlying the association of ALL and ITP are discussed.

PMID- 11342380
TI  - Primary splenic Hodgkin's disease with remarkable granulomatous reaction.

PMID- 11342381
TI  - Isolation of larval behavioral mutants in Drosophila melanogaster.
AB  - Genetic loci that influence behavior are often difficult to identify and localize
      in part due to the quantitative nature of behavioral phenotypes. Previous studies
      had found an association between pupal lethality and altered larval behavior for
      mutants of several genes. To facilitate the identification and localization of
      new mutants that influence larval foraging (movement in the presence of food) and
      general locomotion (movement in the absence of food) behaviors we identified and
      then screened a collection of strains carrying pupal-lethal mutations for
      alterations in these larval behaviors. When the lethal mutation segregated with
      the behavioral alteration this permitted the mapping of the behavioral locus.
      Nine new loci on the second chromosome were found to affect larval behavior. Of
      these, seven loci affected foraging and two affected locomotion. Analyses of
      these new loci will lead to further understanding of the mechanistic bases of
      larval behavior.

PMID- 11342379
TI  - Autologous peripheral blood stem cell transplantation following heart
      transplantation for primary systemic amyloidosis.
AB  - A 47 years old woman was admitted with severe congestive heart failure. Cardiac
      echography showed increased intra-ventricular septum thickness, and there was a
      serum Ig G lambda monoclonal component. Cardiac biopsies confirmed diffuse
      amyloidosis of Al type. To avoid cardiac toxicity of chemotherapy, the patient
      received first a heart transplantation (HT), followed six months later by
      melphalan 200 mg/m(2) and autologous peripheral blood stem cell support (PBSCT).
      This case suggests that such strategy is feasible with a favorable outcome, and
      HT may be an appropriate procedure for some patients with Al amyloidosis who meet
      the criteria for PBSCT.

PMID- 11342382
TI  - Genomic organization of the human metabotropic glutamate receptor subtype 3.
AB  - In this study, the genomic organization of the human metabotropic glutamate
      receptor subtype 3 (mGluR3) gene has been determined. We have identified two
      transcription initiation sites and the polyadenylation signal by using 5'-rapid
      amplification of cDNA ends (RACE) and 3'-RACE, respectively. The exon/intron
      organization of the human mGluR3 gene revealed the presence of 6 exons separated
      by 5 introns. The size of introns varied from 10.4 to 120 kbp that contained
      consensus sequences for repetitive elements such as Alu and long interspersed
      elements. A putative promoter region flanking the 5' sequence of exon 1 was
      identified by computer-aided analysis. The putative promoter region was
      characterized by the presence of a CAAT and GC box, and the absence of a TATA box
      or CpG islands. Several putative binding sites for transcription factors were
      also identified. In addition, we have isolated, from a mouse genomic library,
      part of the mouse mGluR3 gene and found it to correspond to exon 2 in the human
      mGluR3 gene. The mouse mGluR3 gene was then mapped by fluorescent in situ
      hybridization analysis to chromosome 5qA2.

PMID- 11342383
TI  - The effects of ectopic white and transformer expression on Drosophila courtship
      behavior.
AB  - The sex determining genes of Drosophila males and females function to establish
      the potential for sex-specific behaviors. Previous studies suggest that ectopic
      GAL4-directed misexpression of the female-specific isoform of the sex-determining
      gene transformer (tra) in specific sub-domains of an otherwise male brain can
      lead to bisexual courtship behavior, thus identifying brain domains that may
      mediate sex-specific behavior. However, expression of mini-white, the marker gene
      used in both P[GAL4] and P[UAS(G)] constructs, also induces males to court other
      males, questioning whether GAL4-mediated tra expression alone can induce bisexual
      behavior. Here we demonstrate the consequences of inducing mutations in the mini
      white genes within P[GAL4] and P[UAS(G)] constructs to generate flies in which a
      white mutant phenotype is revealed. In these mini-white mutant strains, P[GAL4]
      mediated transformer expression alone is both sufficient and necessary to
      generate bisexual behavior. In addition, using RT-PCR, we reveal the presence of
      female transcripts of doublesex and fruitless in the brains of otherwise male
      (XY) flies exhibiting P[GAL4]-directed tra-expression, demonstrating that P[GAL4]
      directed tra is functional at the molecular level. We conclude that P[GAL4]
      directed misexpression of tra is responsible for the bisexual behavior previously
      described and that this is mediated via sex-specific splicing of dsx and fru. Our
      results support the validity of such strategies for identifying regions of the
      fly brain that underlie sex-specific behaviors.

PMID- 11342384
TI  - Molecular and behavioral analysis of sex-linked courtship song variation in a
      natural population of Drosophila melanogaster.
AB  - Genes controlling the "lovesong" in Drosophila are particularly interesting under
      a evolutionary point of view as they could be involved in the reproductive
      isolation between closely related species and, as a consequence, in the
      speciation process. We carried out a survey of sex-linked molecular and
      behavioral courtship song variation in 27 lines derived from a natural population
      of Drosophila melanogaster in Italy. We sequenced a 983 bp fragment of
      cacophony(cac), a calcium channel gene controlling aspects of the courtship song.
      The same region was also sequenced in a D. simulans strain. Only 5 non-coding
      sites were polymorphic among the D. melanogaster lines, and no amino acid
      substitutions were found between the two species. Statistical tests applied to
      the data did not reveal any significant deviations from a neutral model. Using
      the same lines we also carried out an analysis of three different song parameters
      which are known to be affected by the cac(S) song mutation: interpulse-interval
      (IPI), pulse amplitude (PA) and cycles per pulse (CPP). We found significant
      differences among the lines in IPI and PA, and for the latter a significant
      association with one of the polymorphic sites of cac.

PMID- 11342385
TI  - The status of SCA1, MJD/SCA3, FRDA, DRPLA and MD triplet containing genes in
      patients with Huntington disease and healthy controls.
AB  - A number of human hereditary neuromuscular and neurodegenerative disorders are
      caused by the expansion of trinucleotide repeats within certain genes. Here we
      report the results of the analysis of five trinucleotide repeats containing genes
      (SCA1, MJD/SCA3, DRPLA, FRDA and MD) in HD patients and in a group of healthy
      controls. Allelic frequency distributions for SCA1 and FRDA genes were shifted
      toward larger alleles in the group of unrelated HD patients, compared to healthy
      controls. This linkage disequilibrium suggests a possible existence of a common
      mechanism of trinucleotide repeats expansion in these loci.

PMID- 11342387
TI  - Voltage-dependent effects of Ca(2+)/calmodulin on Cl(-) channel in cardiac
      sarcoplasmic reticulum.
AB  - A new kind of chloride channels in the cardiac sarcoplasmic reticulum, 116 pS Cl(
      ) channel (500 mM Cl(-) in the cis and 50 mM Cl(-) in the trans chamber
      solutions), which is activated by protein-kinase-A-dependent phosphorylation, has
      been determined to conduct adenine nucleotide as a transporter between cytosol
      and SR lumen. We investigated the voltage-dependent gating of this Cl(-) channel
      by recording single-channel activities using the planar lipid bilayer-vesicle
      fusion technique. The channel activities did not change at different membrane
      potentials (-100 mV to +50 mV) or different Ca(2+) concentrations (1 nM to 1 mM)
      in cis solution. In the presence of calmodulin (CaM) (0.1 microM /microg SR
      vesicles), however, Ca(2+) added to the cis solution at 0 mV inhibited channel
      openings in a Ca(2+) -concentration-dependent manner. These effects were
      prevented by the addition of CaM inhibitors. The blocking effects of CaM differed
      depending on the membrane potentials at negative potentials below -20 mV. With
      CaM and 3 microM Ca(2+), the values of opening probability were 0 at -80 mV, 0.2
      at -40 mV, 0.3 at -20 mV, 0.71 at 0 mV and 0.92 at +20 mV. These results may
      indicate the membrane potential affects the action of Ca(2+) /CaM complex

PMID- 11342386
TI  - Alpha-adrenoceptor stimulation induces hypertrophy and increases L-type calcium
      current density in neonatal rat ventricular cardiomyocytes in culture.
AB  - Effects of chronic alpha-adrenoceptor stimulation on hypertrophy and L-type
      calcium current (I(Ca-L) ) were investigated in neonatal rat ventricular
      cardiomyocytes in culture using whole-cell patch-clamp technique and measurement
      of protein- and RNA-to-DNA ratios. Chronic exposure to norepinephrine (2 microM)
      plus propranolol (2 microM) of cardiomyocytes during 1 and 3 days in culture
      increased cell membrane capacitance, protein- and RNA-to DNA ratios and was
      accompanied by an increase in I(Ca-L) density. These effects were not observed in
      the presence of prazosin (2 microM) suggesting that they could be due to alpha(1)
      -adrenoceptor stimulation. They were also prevented by cycloheximide (5 microM)
      and actinomycin D (1 microM). These effects were not observed in 1 and 3 day
      cultured cells pre-treated for only 1 hour with norepinephrine. They were
      potentiated when calcium concentration was increased in the culture medium and,
      in contrast they were abolished in the presence of the L-type calcium current
      inhibitor, nifedipine (2 microM). The present study demonstrates that hypertrophy
      induced by long-term stimulation of alpha(1) -adrenoceptors is accompanied by an
      increase in the expression of functional calcium channels in neonatal rat
      cardiomyocytes. These results reveal the existence of a novel alpha(1) -mediated
      positive regulation of L-type calcium current different from that due to acute
      stimulation of alpha(1) -adrenoceptors in neonatal ventricular cardiomyocytes.

PMID- 11342390
TI  - Possible influence of intramolecular hydrogen bonds on the three-dimensional
      structure of polyamine amides and their interaction with ionotropic glutamate
      receptors.
AB  - Polyamine amides are potent antagonists of many classes of ionotropic receptor.
      Here, calculations of the conformations of 26 polyamine amides using molecular
      mechanics methodology have shown that intramolecular hydrogen bonds strongly
      influence the in vacuo three-dimensional structure of a polyamine amide. Although
      these bonds are less stable in an aqueous environment, they may occur more when a
      polyamine amide interacts with a binding site. The estimated three-dimensional
      structures of polyamine amides provide an explanation for the differences in
      their antagonist potency at quisqualate-sensitive ionotropic glutamate receptors
      (qGluR) observed in experimental studies. Relative antagonist potency at qGluR is
      correlated with the number of free amino groups on a polyamine amide, i.e. those
      not involved in intramolecular hydrogen bonds. Also, intramolecular hydrogen
      bonds significantly restrict the conformational freedom of the uncharged moiety
      of a polyamine amide. Docking of polyamine amides to a molecular model of a
      mammalian AMPA receptor (GluR1) channel shows that intramolecular H-bonds may
      also provide a good structural explanation for the action of these compounds at
      this site.

PMID- 11342388
TI  - Functional domains of delta- and mu-opioid receptors responsible for adenylyl
      cyclase inhibition.
AB  - Opioid receptors (delta, mu) belong to the large superfamily of G protein coupled
      receptors that inhibit adenylyl cyclase. We have studied the effects of seven
      synthetic peptides representing selected cytoplasmic regions of the murine delta
      opioid receptor on forskolin-mediated adenylyl cyclase activity in membranes of
      D2 and Neuro(2A) cells stably expressing the delta- and mu-opioid receptors
      respectively. The entire third intracellular loop (i3), its amino-terminal
      portion (i3.1) and the carboxyl-terminal region of the second cytoplasmic loop
      (i2.2) enhanced dose-dependently the agonist-mediated inhibition of cAMP
      accumulation. The peptide-mediated effects are blocked by pertussis toxin
      treatment and are not observed in parental cells that lack these receptors. The
      inhibitory effects of the peptides on adenylyl cyclase were markedly attenuated
      when membranes from D2 and Neuro(2A) cells were preincubated with antisera
      against Gi(2) alpha and G beta subunits of G proteins. Our results provide
      evidence on domains of the delta- and mu-opioid receptors responsible for
      adenylyl cyclase inhibition.

PMID- 11342389
TI  - Monospecific antibodies as probes for the stoichiometry of recombinant GABA(A)
      receptors.
AB  - GABA(A) receptors composed of alpha1beta3 gamma2 and alpha1beta3 subunits were
      expressed in insect Sf9 cells and solubilized in 1% Triton X100. In sucrose
      density gradients, [3H]-Ro15-1788 binding activity, in the case of alpha1beta3
      gamma2, and [3H]-muscimol binding activity, in the case of alpha1beta3 containing
      receptors sedimented as a single sharp peak suggesting the formation of receptors
      containing a defined number of subunits. When alpha1beta3gamma2 -containing
      receptors were incubated with an alpha-subunit specific antibody (bd24), a single
      class of antibody receptor complex was formed irrespective of the receptor
      antibody ratio. This is consistent with two alpha subunits cross-linked within
      the receptor by the antibody. Similar results were obtained using a beta-subunit
      specific antibody (bd17). Several classes of antibody-receptor complex were
      formed when receptors were pre-incubated with a gamma specific antibody (anti
      gamma(2) 1-15 Cys). This profile is consistent with the presence of a single
      gamma subunit in each complex. Experiments with alpha1beta3 subunit containing
      receptors and antibody bd24 produced a profile similar to that seen with
      alpha1beta3 gamma2 receptors, consistent with two alpha subunits per receptor
      complex. In this case, the anti-beta subunit antibody, bd17, produced a unique
      and complex profile consistent with three beta subunits per receptor. This method
      permits the rapid determination of subunit stoichiometries of homogeneous
      receptor populations

PMID- 11342391
TI  - Evidence for voltage-gated potassium channel beta-subunits with oxidoreductase
      motifs in human and rodent pancreatic beta cells.
AB  - Voltage-gated K(+) channel alpha subunits (K(V) alpha) have been previously
      identified in pancreatic islet beta-cells where it has been suggested they have a
      role in membrane repolarization and insulin secretion. Here we report the cloning
      of the three mammalian K(V) beta subunits, including splice variants of these
      subunits, from both human and rat pancreatic islets and from the rat insulinoma
      cell line INS-1. Two of the splice variants, K(V) beta1a and K(V) beta3,
      previously reported to be neuronal tissue specific, are expressed in islets and
      INS-1 cells. In addition, a splice variant of K(V) beta2 that lacks two potential
      protein kinase C phosphorylation sites at the amino terminus is present.
      Immunoblot analysis suggests a high level of K(V) beta2 subunit protein in rat
      pancreatic islets and immunoprecipitation with anti-K(V) beta2 antibody pulls
      down a protein from INS-1 cells that reacts with anti-aldose reductase antibody.
      The K(V) beta subunits, which are attached to the cytoplasmic face of the alpha
      subunits and are members of the aldose reductase superfamily of NADPH
      oxidoreductases, may have an as yet undetermined role in the regulation of
      insulin secretion by the intracellular redox potential. Finally, we suggest that
      a systematic nomenclature for K(V) beta subunits first proposed by McCormack et
      al. be adopted for this family of potassium channel subunits as it corresponds
      with the nomenclature used for their cognate K(V) alpha subunits.

PMID- 11342393
TI  - Activity-stress increases density of GFAP-immunoreactive astrocytes in the rat
      hippocampus.
AB  - Although past research has indicated that stress and the accompanying increase in
      glucocorticoids compromises hippocampal neurons, little is known about the effect
      of stress on hippocampal glial cells. In the current study, male rats were
      exposed to activity-stress (A-S) for six days; this comprised housing with an
      activity wheel and restricted access (1h/day) to food. Physiological data (e.g.,
      relative adrenal and thymus weights, gastric ulceration) suggested that the A-S
      rats experienced more stress than pair-fed (no wheel) and control (fed ad
      libitum, no wheel) rats. Whereas stress did not influence the quantitative
      morphology of glial fibrillary acidic protein (GFAP)-immunoreactive cells, a semi
      quantitative analysis revealed that the A-S rats had significantly more (30%)
      GFAP-immunoreactive cells in the hippocampal CA3 region than the control rats.
      Based on the present findings, it appears that the hippocampal astrocytic
      response to chronic stress may be similar to the response found in endangered, or
      challenged hippocampal environments, such as in ischemia.

PMID- 11342392
TI  - Persistent neuroendocrine changes in multiple hormonal axes after a single or
      repeated stressor exposures.
AB  - Many researchers have studied acute responses to stress in animals and how they
      are modified by prior stressor exposure, but relatively few have examined whether
      responses to stressors might last for prolonged periods of time. We have
      previously demonstrated that trough plasma corticosterone levels in rats are
      elevated for three to five days after single or repeated exposures to mild
      restraint and inescapable tailshock. The current study measured other aspects of
      the adrenal axis, and activity in other neuroendocrine systems, 24 hours after
      one or three consecutive exposures to the same stress paradigm. The data
      indicated persistent activation of the adrenal axis and prolactin levels, whereas
      the thyroid and reproductive hormone axes were inhibited after either one or
      three stress sessions. These changes are remarkable in that one would have
      expected acute responses to even intense stressors to have ended within hours
      after the end of the stressor. It will be important to understand the
      interactions among these responding neuroendocrine systems and to know how long
      such persistent changes last. Finally, it will be critical to understand the
      relative contributions of neuroendocrine and psychological factors in maintaining
      these persistent neuroendocrine changes after exposure to intense stressors.

PMID- 11342394
TI  - Plasma corticosterone and immune reactivity in restrained female C3H mice.
AB  - Psychological stressors are known to stimulate the hypothalamic-pituitary-adrenal
      axis and the sympathetic nervous system resulting in the release of
      corticosterone and catecholamines respectively. They have also been reported to
      induce cytokine production. All these molecules affect various immune parameters
      and can alter overall immune competence of the individual. The purpose of this
      investigation was to study the regulation of the production of corticosterone
      during stress and its possible effects on immune reactivity. In a first series of
      experiments, the possible regulation of corticosterone production by interleukin
      (IL)-1beta and peripheral catecholamines during restraint was assessed using a
      pharmacological approach in mice. Plasma IL-1beta concentrations remained at
      basal after 1-h restraint and the stress-induced increase of plasma
      corticosterone was not modified by a peripheral injection of an IL-1 receptor
      antagonist (IL-1ra). By contrast, chemical sympathectomy potentiated the
      restraint-induced increase in plasma corticosterone concentration, this
      potentiation being reversed by IL-1ra. In a second series of experiments, the
      role of corticosterone in stress-immune relationships was studied in
      adrenalectomized mice subjected to restraint and immunized with sheep
      erythrocytes. Non-specific immunity, i.e. proliferation of splenocytes and
      thymocytes and plasma levels of IL-1beta, as well as specific immunity, i.e.
      antibody production and delayed hypersensitivity, were not altered after 2-h
      restraint. Adrenalectomy failed to induce immune effects in stressed animals,
      except that delayed hypersensitivity was stronger in adrenalectomized animals,
      revealing that the high levels of corticosterone produced during stress have an
      anti-inflammatory activity. The present data show that the stress-induced
      production of corticosterone was modulated by both peripheral catecholamines and
      IL-1beta. However, this production of corticosterone was unable to modulate
      immune reactivity except delayed hypersensitivity.

PMID- 11342395
TI  - The effect of stress and in vivo vasoactive intestinal peptide (VIP) treatment on
      the response of isolated rat aorta to norepinephrine, angiotensin II and
      vasopressin, and adventitial mast cells.
AB  - The effects of cold-restraint stress, repeated over 3 days, and treatment of rats
      with vasoactive intestinal peptide (VIP) on the contractile responses of isolated
      aorta to vasoconstrictors, and on aortic adventitial mast cells were
      investigated. Stress significantly reduced the contractile response of rat aorta
      smooth muscle to norepinephrine (NE), angiotensin II (Ang II) and vasopressin
      (VP). Decreased sensitivity to NE, Ang II and VP may result from decreased
      receptor density, and affinity or reduced effector efficacy. Stress induced
      degranulation, decreased the number and changed the granular content of mast
      cells; all degranulated mast cells were stained with alcian blue, and the
      percentage of safranin staining cells was decreased. Given prior to stress, VIP
      reversed the reduced contractile responses and sensitivity of aorta to NE and Ang
      II but had no effect on VP subsensitivity. VIP also inhibited stress-induced
      degranulation of mast cells, and after VIP only alcian blue-stained mast cells
      were seen. When VIP was given to non-stressed rats, the contractile response of
      the aorta to NE, but not Ang II or VP, was increased compared with control. Mast
      cell count was decreased in the adventitia of non-stressed VIP treated rats. The
      results indicate that stress decreases the heparin content of mast cells and VIP
      has an additive effect. In conclusion, VIP modulates both stress-induced mast
      cell activity and reduced sensitivity of aorta smooth muscle to NE and Ang II. It
      can be suggested that VIP may moderate some effects of stress on vascular
      pathophysiology.

PMID- 11342396
TI  - Autonomic ganglionic neurones in rabbits with differing resistance to emotional
      stress.
AB  - The aim of the present study was to evaluate the reactions of autonomic neurones
      of the nodose ganglion of the vagus nerve, and the stellate and superior cervical
      ganglia in rabbits under emotional stress, and to correlate these reactions with
      the individual variations in responses to the stressor. Emotional stress was
      induced in immobilized adult male Chinchilla rabbits by electrical stimulation of
      the ventromedial hypothalamus and skin. During the experiment (3 hours) arterial
      blood pressure (BP) was recorded. Metabolic activities of the stellate and
      superior cervical sympathetic ganglia and nodose ganglion were measured as
      contents of biogenic amines and their synthesizing and degrading enzymes,
      neuronal size and dry mass and total RNA; these corresponded to the changes in
      BP. One group of rabbits showed small fluctuations of BP throughout the
      experiment and were defined as resistant to stress, whereas in the other group
      (predisposed to stress) BP progressively decreased. In the former, there was a
      smaller increase of sympathetic and nodose ganglia metabolic activity than in the
      latter, in which changes included reduced neuronal dry mass, increased RNA
      content compared with controls, and reduced tyrosine hydroxylase activity and
      increased norepinephrine content compare with controls and stress- resistant
      rabbits. The predisposed rabbits showed earlier and greater increases in
      circulating norepinephrine concentrations than the resistant rabbits, indicating
      sustained sympathetic activation. The data indicate that the ganglia of the
      sympathetic nervous system are part of a major mechanism of BP regulation under
      acute experimental emotional/painful stress. The nodose ganglion participates in
      the maintenance of stable cardiovascular function in extreme conditions.

PMID- 11342397
TI  - Cardiovascular responses to open-field stress in rats: sex differences and
      effects of gonadal hormones.
AB  - We studied sex differences in cardiovascular responses to stress using a new
      radio-telemetry model in which freely-moving Spontaneously Hypertensive rats
      (SHR) are exposed to open-field novelty stress. This model allowed simultaneous
      assessment of cardiovascular and behavioural responses to psychological stress.
      Female SHR in the diestrous stage of their estrous cycle had markedly greater
      pressor and tachycardic responses to open-field exposure when compared to either
      female rats not in diestrous or male SHR. Treatment of ovariectomized SHR with
      estrogen alone had no significant effect on cardiovascular reactivity, while a
      combined treatment of estrogen and progesterone slightly, but significantly
      attenuated their pressor response to open-field stress. In addition, treatment of
      castrated male rats with testosterone significantly enhanced their pressor
      responses to stress when compared to values obtained before treatment. None of
      the hormone treatments had any significant effect on heart rate responses to
      stress. Neither at different stages of the estrous cycle nor after hormone
      treatments were there any marked changes in behavioural responses in the open
      field, making it unlikely that the differences in cardiovascular stress responses
      were caused by changes in behavioural activity. These data demonstrate
      differences in cardiovascular stress responses that seem to be dependent on the
      stage of the estrous cycle. They suggest that particularly androgens, such as
      testosterone, may enhance pressor responses to stress. On the other hand, a
      combination of estrogen and progesterone, rather than estrogen alone, may have a
      small attenuating effect on cardiovascular reactivity.

PMID- 11342398
TI  - Holisitic nursing: taking your practice to the next level.
AB  - The goal of holistic nursing is to enhance healing of the whole person from birth
      to death. The new American Holistic Nursing Association's (AHNAs) Standards of
      Holistic Nursing Practice defines the ways to accomplish this goal, describing
      the scope of holistic nursing practice and the level of care expected from a
      holistic nurse. Nurses can reduce the devastating effects of crisis and illness
      in individuals by using the AHNA standards of practice. As nurses integrate
      interdiciplinarity into their work and think at the intersections, the human
      story enfolds in a new way, and health moves into the domain of healing.

PMID- 11342399
TI  - Nurturing and caring for self.
AB  - As instruments of healing, nurses commonly provide therapeutic counseling, but
      often do not heed their own advice for self-care. To give to others, nurses need
      to nourish all aspects of self. The self extends far beyond the needs of the
      physical body. Therefore, giving of the self requires self-nurturance of the
      physical, mental, emotional, and spiritual aspects. This article describes how to
      nurture and care for the self.

PMID- 11342400
TI  - Characteristics of spirituality, assessment, and prayer in holistic nursing.
AB  - There is a rediscovery and interest in spirituality at the outset of the third
      millennium. The challenge will be to harness the spiritual energy naturally
      available so that patients may be healed and not necessarily cured. Engaging in a
      patient's own healing process, nurturing a spirituality of life, learning the
      tools of spiritual assessment, developing ways of praying, being attentive to
      developing caring relationships so as to be an "Anam Cara" or soul friend, and
      networking with other spiritual care professionals are useful resources for the
      holistic nurse.

PMID- 11342401
TI  - Meditation, yoga, and guided imagery.
AB  - The author presents an introduction to insight or mindfulness meditation, yoga,
      and guided imagery from theoretical and practical perspectives. She provides
      clear, easy-to-follow steps to begin using sitting meditation, walking
      meditation, and yoga for the health care provider and for the patient. She
      presents the material first for self-knowledge and self-care and secondarily for
      connecting to others in healing relationships.

PMID- 11342403
TI  - The environment as a healing tool.
AB  - Environmental pollution is a growing concern in developed and developing nations.
      Since the advent of air tight construction, there has been an onset of in
      building allergens and consequent respiratory problems. Solutions exist for
      combating external environmental pollution. A person's awareness about their own
      internal mental environment is necessary for them to address ways to better cope
      with the inevitable external environmental stresses.

PMID- 11342402
TI  - The role of aromatherapy in nursing care.
AB  - Aromatherapy is the fastest growing of all complementary therapies among nurses
      in the United States. Although aromatherapy has been used by the public for
      recreation for thousands of years and by nurses throughout the world during the
      last 15 years, it is only in the last few years that aromatherapy has become
      recognized by US State Boards of Nursing as a legitimate part of holistic
      nursing. Aromatherapy is now set to become one of the most popular tools that
      nurses can use to enhance their nursing care and simultaneously empower
      themselves. This article explores the potential role of aromatherapy in nursing,
      highlights four essential oils, and suggests practical ways that nurses can begin
      using this gentle therapy.

PMID- 11342404
TI  - Music as intervention: a notable endeavor to improve patient outcomes.
AB  - Music interventions have been used in medicine and nursing throughout history.
      Music therapy is an easy-to-administer, relatively inexpensive, noninvasive
      intervention that has been used to reduce heart rate, blood pressure, myocardial
      oxygen consumption, gastrointestinal function, anxiety, and pain. A review of
      theoretic and empirical base for the use of music therapy to improve patient
      outcomes in a variety of areas of clinical practice is presented. Implications
      for practice and future research are suggested.

PMID- 11342405
TI  - Cognitive therapy: applications for health promotion, disease prevention, and
      disease management.
AB  - Cognitive therapy is a short-term therapeutic intervention that can be helpful
      for patients with or at risk for health problems that may be caused or
      exacerbated by stress and has implications for nursing practice across the
      biologic, psychosocial and spiritual domains. This article outlines the
      psychophysiology of stress, examines cognitive therapy as an intervention to
      mediate its harmful effects, reviews clinical situations in which it has been
      shown to be effective, details the steps of the process, and explores the unique
      perspective that nurses bring to its application.

PMID- 11342406
TI  - Listening and focusing: holistic health care tools for nurses.
AB  - This article explores the roles of two methods of holistic communication: active
      listening and focusing. Active listening is a technique used by the nurse to
      reflect on what a patient has said to him or her and can help patients feel more
      deeply and be understood better by the nurse. Focusing, a body-centered method
      for developing self-awareness, is a way of listening to feelings by becoming
      aware of body sensations that carry meaning about issues or concerns. This
      article includes four uses of focusing: (1) reducing stress, (2) creating better
      coping strategies (e.g., pain control, decision making), (3) making behavioral
      changes, and (4) developing a collaborative approach with patients. Clinical
      examples (mini-focusing moments) that demonstrate how listening and focusing may
      be integrated into daily nursing care are also included.

PMID- 11342407
TI  - The journal as a guide for the healing journey.
AB  - The healing influence of the journal is now being recognized through research and
      in the practices of those who are using this modality. The journal is an
      important tool because it works as a catalyst for self-discovery and self
      reflection. As nurses practice holistic living, the journal is a friend that
      helps nurture the self and lifts others to higher levels of empowerment on the
      journey of healing and wellness.

PMID- 11342408
TI  - Healing touch.
AB  - This article explores how nurses can use energetic principles and Healing Touch
      to enhance the healing of their patients, for their own personal healing and
      growth, for improving job satisfaction, and for identifying educational resources
      available for more intense study.

PMID- 11342409
TI  - Massage therapy and reflexology awareness.
AB  - Massage therapy and reflexology are manual therapeutic approaches used to
      facilitate healing and health and can be used by nurses in almost any setting.
      Information about massage therapy and reflexology is shared for the purpose of
      creating awareness about healing modalities and encouraging the use of basic
      techniques of these manual therapies. A review of a case study illustrates the
      safe and effective use of massage therapy and reflexology and familiarizes the
      nurse with the components of assessment and hands-on practice. Holistic nursing
      principles related to massage therapy and reflexology are woven throughout the
      text.

PMID- 11342414
TI  - Ligation of CD11b and CD11c beta(2) integrins by antibodies or soluble CD23
      induces macrophage inflammatory protein 1alpha (MIP-1alpha) and MIP-1beta
      production in primary human monocytes through a pathway dependent on nuclear
      factor-kappaB.
AB  - Chemokines and adhesion molecules such as integrins play a major part in the
      trafficking, extravasation, and recruitment of leukocytes to inflammatory sites.
      This study investigated the effects of beta(2) integrin engagement on chemokine
      production by freshly isolated human monocytes. We found that ligation of CD11b
      or CD11c but not CD11a alpha chains of beta(2) integrins by antibodies or soluble
      CD23 (sCD23) fusion proteins rapidly induced transcription and secretion of
      interleukin 8, macrophage inflammatory protein (MIP) 1alpha, and MIP-1beta.
      Because the promoters of these chemokine genes contain kappaB binding sites, we
      assessed the possible role of nuclear factor-kappaB (NF-kappaB) in controlling
      induction of the genes through beta(2) integrin engagement. Electrophoretic
      mobility shift assays showed that sCD23 or antibodies to CD11b or to CD11c up
      regulated DNA-binding activity of NF-kappaB. Activation of NF-kappaB was
      accompanied by degradation of its cytosolic inhibitor IkappaB-alpha. Blockade of
      depletion of IkappaB-alpha by proteasome inhibitors (proteasome inhibitor I or
      acetyl-leucinyl-leucinyl-norleucinal) led to concomitant inhibition of NF-kappaB
      DNA-binding activity and expression of MIP-1alpha and MIP-1beta messenger RNA
      induced by beta(2) integrin ligation. These results suggest that triggering of
      CD11b or CD11c beta(2) integrin on primary human monocytes provides activation
      signals leading to nuclear translocation of NF-kappaB and subsequent secretion of
      MIP-1alpha and MIP-1beta that may have an important role in recruitment of other
      inflammatory cells during initiation of an inflammatory response.

PMID- 11342413
TI  - Expansion of cytolytic CD8(+) natural killer T cells with limited capacity for
      graft-versus-host disease induction due to interferon gamma production.
AB  - T cells with natural killer cell phenotype and function (NKT cells) have been
      described in both human and murine tissues. In this study, culture conditions
      were developed that resulted in the expansion of CD8(+) NKT cells from bone
      marrow, thymus, and spleen by the timed addition of interferon-gamma (IFN-gamma),
      interleukin 2 (IL-2), and anti-CD3 monoclonal antibody. After 14 to 21 days in
      culture, dramatic expansion of CD3(+), CD8(+), alphabetaT-cell receptor(+) T
      cells resulted with approximately 20% to 50% of the cells also expressing the NK
      markers NK1.1 and DX5. The CD8(+) NKT cells demonstrated lytic activity against
      several tumor target cells with more than 90% lysis by day 14 to day 21 of
      culture. Cytotoxicity was observed against both syngeneic and allogeneic tumor
      cell targets with the greatest lytic activity by the cells expressing either
      NK1.1 or DX5. The expanded CD8(+) NKT cells produce T(H)1-type cytokines with
      high levels of IFN-gamma and tumor necrosis factor alpha. Expansion of the CD8(+)
      NKT cells was independent of CD1d. Ly49 molecules were expressed on only a
      minority of cells. A single injection of expanded CD8(+) NKT cells was capable of
      protecting syngeneic animals from an otherwise lethal dose of Bcl1 leukemia
      cells. Expanded CD8(+) NKT cells produced far less graft-versus-host disease
      (GVHD) than splenocytes across major histocompatibility barriers, even when 10
      times the number of CD8(+) NKT cells as compared to splenocytes were injected.
      This reduction in GVHD was related to IFN-gamma production since cells expanded
      from IFN-gamma knock-out animals caused acute lethal GVHD, whereas cells expanded
      from animals defective in fas ligand, fas, IL-2, and perforin did not. These data
      indicate that CD8(+) NKT cells expanded in this fashion could be useful for
      preserving graft-versus-leukemia activity without causing GVHD.

PMID- 11342415
TI  - The synthetic peptide WKYMVm attenuates the function of the chemokine receptors
      CCR5 and CXCR4 through activation of formyl peptide receptor-like 1.
AB  - The G protein-coupled 7 transmembrane (STM) chemoattractant receptors can be
      inactivated by heterologous desensitization. Earlier work showed that formly
      peptide receptor-like 1 (FPRL1), an STM receptor with low affinity for the
      bacterial chemotactic peptide formyl-methionyl-leucyl-phenylalamine (fMLF), is
      activated by peptide domains derived from the human immunodeficiency virus (HIV)
      1 envelope glycoprotein gp120 and its activation results in desensitization and
      down-regulation of the chemokine receptors CCR5 and CXCR4 from monocyte surfaces.
      This study investigated the possibility of interfering with the function of CCR5
      or CXCR4 as HIV-1 coreceptors by activating FPRL1. Cell lines were established
      expressing FPRL1 in combination with CD4/CXCR4 or CD4/CCR5 and the effect of a
      synthetic peptide, WKYMVm, a potent activator of formyl peptide receptors with
      preference for FPRL1 was determined. Both CXCR4 and CCR5 were desensitized by
      activation of the cells with WKYMVm via a staurosporine-sensitive pathway. This
      desensitization of CXCR4 and CCR5 also attenuated their capacity as the fusion
      cofactors for HIV-1 envelope glycoprotein and resulted in a significant
      inhibition of p24 production by cell lines infected with HIV-1 that use CCR5 or
      CXCR4 as coreceptors. Furthermore, WKYMVm inhibited the infection of human
      peripheral monocyte-derived macrophages and CD4(+) T lymphocytes by R5 or X4
      strains of HIV-1, respectively. These results indicate that heterologous
      desensitization of CCR5 and CXCR4 by an FPRL1 agonist attenuates their major
      biologic functions and suggest an approach to the development of additional anti
      HIV-1 agents. (Blood. 2001;97:2941-2947)

PMID- 11342416
TI  - Larger numbers of CD4(bright) dendritic cells in donor bone marrow are associated
      with increased relapse after allogeneic bone marrow transplantation.
AB  - Relapse is the major cause of death after allogeneic bone marrow transplantation
      (BMT). This study tested the hypothesis that the numbers of donor mononuclear
      cells, lymphocytes, and CD34(+) cells influence relapse and event-free survival
      (EFS) after BMT. The study population consisted of 113 consecutive patients with
      hematologic malignancies who underwent non-T-cell-depleted BMT from HLA-matched
      siblings. Sixty-four patients had low-risk diagnoses (ALL/AML CR1, MDS RA/RARS,
      and CML CP1); 49 patients had high-risk diagnoses (all others). CD34(+) cells, T
      cells, B cells, natural killer cells, monocytes, and a rare population of CD3(-),
      CD4(bright) cells in the allografts were measured by flow cytometry. The CD3(-),
      CD4(bright) cells in bone marrow had the same frequency and phenotype as
      CD123(bright) type 2 dendritic cell (DC) progenitors, and they differentiated
      into typical DCs after short-term culture. Cox regression analyses evaluated risk
      strata, age, gender, and the numbers of nucleated cells, CD3(+) T cells, CD34(+)
      hematopoietic cells, and CD4(bright) cells as covariates for EFS, relapse, and
      nonrelapse mortality. Recipients of larger numbers of CD4(bright) cells had
      significantly lower EFS, a lower incidence of chronic graft-versus-host disease
      (cGVHD), and an increased incidence of relapse. Recipients of larger numbers of
      CD34(+) cells had improved EFS; recipients of fewer CD34(+) cells had delayed
      hematopoietic engraftment and increased death from infections. In conclusion, the
      content of donor CD4(bright) cells was associated with decreased cGVHD and graft
      versus-leukemia effects in recipients of allogeneic bone marrow transplantation,
      consistent with a role for donor DCs in determining immune responses after
      allogeneic BMT.

PMID- 11342417
TI  - Survival after transplantation of unrelated donor umbilical cord blood is
      comparable to that of human leukocyte antigen-matched unrelated donor bone
      marrow: results of a matched-pair analysis.
AB  - Umbilical cord blood (UCB) is being increasingly used for hematopoietic stem cell
      transplantation and has been associated with a reduced incidence of severe graft
      versus-host disease (GVHD). To further investigate the relative merits of
      unrelated donor UCB versus bone marrow (BM), a matched-pair analysis comparing
      the outcomes of recipients of 0 to 3 human leukocyte antigen (HLA)-mismatched UCB
      and HLA-A, B, DRB1-matched BM was performed. UCB patients, who received
      cyclosporine (CSA) and methylprednisolone (MP), were matched for age, diagnosis,
      and disease stage with BM patients, who received either methotrexate (MTX) and
      CSA (26 pairs) or T-cell depletion (TCD) and CSA/MP (31 pairs). Patients were
      predominantly children (median age, 5 years) undergoing transplantation for
      malignancy, storage diseases, BM failure, and immunodeficiency syndromes between
      1991 and 1999. Although neutrophil recovery was significantly slower after UCB
      transplantation, the probability of donor-derived engraftment at day 45 was 88%
      in UCB versus 96% in BM-MTX recipients (P =.41) and 85% in UCB versus 90% in BM
      TCD recipients (P =.32), respectively. Platelet recovery was similar in UCB
      versus BM pairs. Furthermore, incidences of acute and chronic GVHD were similar
      in UCB and BM recipients, with 53% of UCB versus 41% of BM-MTX recipients alive
      (P =.40) and 52% of UCB versus 56% of BM-TCD recipients alive at 2 years (P
      >.80), respectively. These data suggest that despite increased HLA disparity,
      probabilities of engraftment, GVHD, and survival after UCB transplantation are
      comparable to those observed after HLA-matched BM transplantation. Therefore, UCB
      should be considered an acceptable alternative to HLA-matched BM for pediatric
      patients.

PMID- 11342418
TI  - Comparison of outcomes of unrelated bone marrow and umbilical cord blood
      transplants in children with acute leukemia.
AB  - In order to compare the outcomes of unrelated umbilical cord blood transplants
      (UCBTs) or bone marrow transplants, 541 children with acute leukemia (AL)
      transplanted with umbilical cord blood (n = 99), T-cell-depleted unrelated bone
      marrow transplants (T-UBMT) (n = 180), or nonmanipulated (UBMT) (n = 262), were
      analyzed in a retrospective multicenter study. Comparisons were performed after
      adjustment for patient, disease, and transplant variables. The major difference
      between the 3 groups was the higher number in the UCBT group of HLA mismatches
      (defined by serology for class I and molecular typing for DRB1). The donor was
      HLA mismatched in 92% of UCBTs, in 18% of UBMTs, and in 43% of T-UBMTs (P <.001).
      Other significant differences were observed in pretransplant disease
      characteristics, preparative regimens, graft-versus-host disease (GVHD)
      prophylaxis, and number of cells infused. Nonadjusted estimates of 2-year
      survival and event-free survival rates were 49% and 43%, respectively, in the
      UBMT group, 41% and 37% in the T-UBMT group, and 35% and 31% in the UCBT group.
      After adjustment, differences in outcomes appeared in the first 100 days after
      the transplantation. Compared with UBMT recipients, UCBT recipients had delayed
      hematopoietic recovery (Hazard ratio [HR] = 0.37; 95% confidence interval [95CI]:
      0.27-0.52; P <.001), increased 100 day transplant-related mortality (HR = 2.13;
      95CI: 1.20-3.76; P <.01) and decreased acute graft-versus-host disease (aGVHD)
      (HR = 0.50; 95CI: 0.34-0.73; P <.001). T-UBMT recipients had decreased aGVHD (HR
      = 0.25; 95CI: 0.17-0.36; P <.0001) and increased risk of relapse (HR = 1.96;
      95CI: 1.11-3.45; P =.02). After day 100 posttransplant, the 3 groups achieved
      similar results in terms of relapse. Chronic GVHD was decreased after T-UBMT (HR
      = 0.21; 95CI: 0.11-0.37; P <.0001) and UCBT (HR = 0.24; 95CI: 0.01-0.66; P
      =.002), and overall mortality was higher in T-UBMT recipients (HR = 1.39; 95CI:
      0.97-1.99; P <.07). In conclusion, the use of UCBT, as a source of hematopoietic
      stem cells, is a reasonable option for children with AL lacking an acceptably
      matched unrelated marrow donor.

PMID- 11342419
TI  - Highly heterogeneous nature of delta-aminolevulinate dehydratase (ALAD)
      deficiencies in ALAD porphyria.
AB  - The properties of 9 delta-aminolevulinate dehydratase (ALAD) mutants from
      patients with ALAD porphyria (ADP) were examined by bacterial expression of their
      complementary DNAs and by enzymologic and immunologic assays. ALADs were
      expressed as glutathione-S-transferase (GST) fusion proteins in Escherichia coli
      and purified by glutathione-affinity column chromatography. The GST-ALAD fusion
      proteins were recognized by anti-ALAD antibodies and were enzymatically active as
      ALAD. The enzymatic activities of 3 ALAD mutants, K59N, A274T, and V153M, were
      69.9%, 19.3%, and 41.0% of that of the wild-type ALAD, respectively, whereas 6
      mutants, G133R, K59N/G133R, F12L, R240W, V275M, and delTC, showed little activity
      (< 8%). These variations generally reflect the phenotype of ALAD in vivo in
      patients with ADP and indicate that GST-ALAD fusion protein is indeed useful for
      predicting of the phenotype of ALAD mutants. The location of F12L mutation in the
      enzyme's molecular structure indicates that its disturbance of the quaternary
      contact of the ALAD dimer appears to have a significant influence on the
      enzymatic activity. Mouse monoclonal antibodies to human ALAD were developed that
      specifically recognized a carboxy terminal portion of ALAD, or other regions in
      the enzyme. This study represents the first complete analysis of 9 mutants of
      ALAD identified in ADP and indicates the highly heterogeneous nature of mutations
      in this disorder.

PMID- 11342420
TI  - Polymorphisms of clotting factors modify the risk for primary intracranial
      hemorrhage.
AB  - Intracranial hemorrhage is the third most frequent cause of cerebrovascular
      disease, but few genetic risk factors have been associated with its development.
      Recently, it has been reported that some polymorphisms that affect clotting
      factors increase the risk for thrombosis. However, reports have analyzed the
      effect of polymorphisms influencing the hemostatic state in bleeding disorders
      insufficiently. A case-control study was conducted of 201 patients with
      spontaneous intracranial hemorrhage and 201 control subjects matched for age,
      race, sex, and selected risk factors (hypertension, smoking, and alcohol
      consumption). Genomic polymerase chain reaction was used to analyze the
      prevalence of 4 polymorphisms: factor V Leiden, prothrombin 20210A, factor VII
      323 Del/Ins of a decanucleotide, and factor XIII V34L. Subjects with factor V
      Leiden had decreased risk for spontaneous intracranial hemorrhage (odds ratio,
      0.19; 95% confidence interval, 0.03-0.95). The frequency of the prothrombin
      20210A/G genotype was also lower among patients than controls (1.5% vs 3%,
      respectively). Moreover, carriers of the -323 Ins allele of factor VII had a 1.54
      fold risk for intracranial hemorrhage (95% CI, 1.03-2.72). Finally, no
      significant differences were observed in the prevalence of factor XIII V34L
      polymorphism between patients and controls. Therefore, new genetic factors
      affecting the risk for spontaneous intracranial hemorrhage were identified. These
      data, together with the relevance of these polymorphisms in thrombotic diseases,
      support the idea that a polymorphism may play opposite roles in thrombosis and
      hemorrhage, suggesting an explanation for the high frequency of these
      polymorphisms in the general population.

PMID- 11342421
TI  - A potential role for interleukin-7 in T-cell homeostasis.
AB  - Interleukin (IL)-7 is known to up-regulate thymopoietic pathways of T-cell
      regeneration. Recent work also has shown it to potently enhance thymic
      independent peripheral expansion and to restore immunocompetence in athymic T
      cell-depleted hosts. We hypothesized that endogenous IL-7 could contribute to the
      restoration of T-cell homeostasis following T-cell depletion. To analyze this, we
      evaluated circulating IL-7 levels and lymphocyte subsets in multiple clinical
      cohorts with T-cell depletion of varying etiologies. In pediatric (n = 41) and
      adult (n = 51) human immunodeficiency virus-infected CD4-depleted patients, there
      were strong inverse correlations between IL-7 levels and CD4 counts (r = -0.77, P
      <.0001, and r = -0.68, P <.0001). Declines in IL-7 were temporally correlated
      with recovery of CD4 counts. Similar patterns were observed in CD4-depleted
      patients receiving cancer chemotherapy (r = -0.65, P =.009). Therefore, in 2
      disparate clinical scenarios involving CD4 depletion, IL-7 levels dynamically
      respond to changes in CD4 T-cell number, making this cytokine uniquely suited as
      a candidate regulator of T-cell homeostasis. Furthermore, in patients with
      idiopathic CD4 lymphopenia, a much weaker relationship between IL-7 levels and
      peripheral blood CD4 counts was observed, suggesting that an impaired IL-7
      response to CD4 depletion may contribute to the impaired lymphocyte homeostasis
      observed in this population. In light of the known effects of IL-7 on T-cell
      regeneration, we postulate that increased availability of IL-7 could play a
      critical role in restoring T-cell homeostasis following T-cell depletion.

PMID- 11342422
TI  - Mitoxantrone is superior to doxorubicin in a multiagent weekly regimen for
      patients older than 60 with high-grade lymphoma: results of a BNLI randomized
      trial of PAdriaCEBO versus PMitCEBO.
AB  - A prospective, multicenter, randomized trial was undertaken to compare the
      efficacy and toxicity of adriamycin with mitoxantrone within a 6-drug combination
      chemotherapy regimen for elderly patients (older than 60 years) with high-grade
      non-Hodgkin lymphoma (HGL) given for a minimum of 8 weeks. A total of 516
      previously untreated patients aged older than 60 years were randomized to receive
      1 of 2 anthracycline-containing regimens: adriamycin, 35 mg/m(2) intravenously
      (IV) on day 1 (n = 259), or mitoxantrone, 7 mg/m(2) IV on day 1 (n = 257); with
      prednisolone, 50 mg orally on days 1 to 14; cyclophosphamide, 300 mg/m(2) IV on
      day 1; etoposide, 150 mg/m(2) IV on day 1; vincristine, 1.4 mg/m(2) IV on day 8;
      and bleomycin, 10 mg/m(2) IV on day 8. Each 2-week cycle was administered for a
      minimum of 8 weeks in the absence of progression. Forty-three patients were
      ineligible for analysis. The overall and complete remission rates were 78% and
      60% for patients receiving PMitCEBO and 69% and 52% for patients receiving
      PAdriaCEBO (P =.05, P =.12, respectively). Overall survival was significantly
      better with PMitCEBO than PAdriaCEBO (P =.0067). However, relapse-free survival
      was not significantly different (P =.16). At 4 years, 28% of PAdriaCEBO patients
      and 50% of PMitCEBO patients were alive (P =.0001). Ann Arbor stage III/IV, World
      Health Organization performance status 2-4, and elevated lactate dehydrogenase
      negatively influenced overall survival from diagnosis. In conclusion, the
      PMitCEBO 8-week combination chemotherapy regimen offers high response rates,
      durable remissions, and acceptable toxicity in elderly patients with HGL.

PMID- 11342423
TI  - A randomized comparison between rasburicase and allopurinol in children with
      lymphoma or leukemia at high risk for tumor lysis.
AB  - Standard therapy in the United States for malignancy-associated hyperuricemia
      consists of hydration, alkalinization, and allopurinol. Urate oxidase catalyzes
      the enzymatic oxidation of uric acid to a 5 times increased urine soluble
      product, allantoin. Rasburicase is a new recombinant form of urate oxidase
      available for clinical evaluation. This multicenter randomized trial compared
      allopurinol to rasburicase in pediatric patients with leukemia or lymphoma at
      high risk for tumor lysis. Patients received the assigned uric acid-lowering
      agent for 5 to 7 days during induction chemotherapy. The primary efficacy end
      point was to compare the area under the serial plasma uric acid concentration
      curves during the first 96 hours of therapy (AUC(0-96)). Fifty-two patients were
      randomized at 6 sites. In an intent-to-treat analysis, the mean uric acid AUC(0
      96) was 128 +/- 70 mg/dL.hour for the rasburicase group and 329 +/- 129
      mg/dL.hour for the allopurinol group (P <.0001). The rasburicase versus
      allopurinol group experienced a 2.6-fold (95% CI: 2.0-3.4) less exposure to uric
      acid. Four hours after the first dose, patients randomized to rasburicase
      compared to allopurinol achieved an 86% versus 12% reduction (P <.0001) of
      initial plasma uric acid levels. No antirasburicase antibodies were detected at
      day 14. This randomized study demonstrated more rapid control and lower levels of
      plasma uric acid in patients at high risk for tumor lysis who received
      rasburicase compared to allopurinol. For pediatric patients with advanced stage
      lymphoma or high tumor burden leukemia, rasburicase is a safe and effective
      alternative to allopurinol during initial chemotherapy.

PMID- 11342424
TI  - Efficient retrovirus-mediated PIG-A gene transfer and stable restoration of GPI
      anchored protein expression in cells with the PNH phenotype.
AB  - Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal hematopoietic stem cell
      disorder characterized by complement-mediated hemolysis due to deficiencies of
      glycosylphosphatidylinositol-anchored proteins (GPI-APs) in subpopulations of
      blood cells. Acquired mutations in the X-linked phosphatidylinositol glycan-class
      A (PIG-A) gene appear to be the characteristic and pathogenetic cause of PNH. To
      develop a gene therapy approach for PNH, a retroviral vector construct, termed
      MPIN, was made containing the PIG-A complementary DNA along with an internal
      ribosome entry site and the nerve growth factor receptor (NGFR) as a selectable
      marker. MPIN transduction led to efficient and stable PIG-A and NGFR gene
      expression in a PIG-A-deficient B-cell line (JY5), a PIG-A-deficient K562 cell
      line, an Epstein-Barr virus-transformed B-cell line (TK-14(-)) established from a
      patient with PNH, as well as peripheral blood (PB) mononuclear cells from a
      patient with PNH. PIG-A expression in these cell lines stably restored GPI-AP
      expression. MPIN was transduced into bone marrow mononuclear cells from a patient
      with PNH, and myeloid/erythroid colonies and erythroid cells were derived. These
      transduced erythroid cells restored surface expression of GPI-APs and resistance
      to hemolysis. These results indicate that MPIN is capable of efficient and stable
      functional restoration of GPI-APs in a variety of PIG-A-deficient hematopoietic
      cell types. Furthermore, MPIN also transduced into PB CD34(+) cells from a normal
      donor, indicating that MPIN can transduce primitive human progenitors. These
      findings set the stage for determining whether MPIN can restore PIG-A function in
      multipotential stem cells, thereby providing a potential new therapeutic option
      in PNH.

PMID- 11342425
TI  - Shwachman-Diamond syndrome marrow cells show abnormally increased apoptosis
      mediated through the Fas pathway.
AB  - Shwachman-Diamond syndrome (SDS) is an inherited bone marrow disorder with
      varying cytopenias and a strong predilection to myelodysplastic syndrome (MDS)
      and acute myeloid leukemia. Previously, it was found that the percentage of
      CD34(+) cells in bone marrow and the in vitro colony formation from CD34(+) cells
      of patients with SDS were markedly reduced. For these reasons, and because
      apoptosis is central in the pathogenesis of bone marrow dysfunction in MDS, this
      study was initiated to delineate the role of apoptosis in the pathogenesis of the
      marrow failure. Eleven children with SDS were studied. Compared to normal
      controls, patients' marrow mononuclear cells plated in clonogenic cultures showed
      a significantly higher tendency to undergo apoptosis. The defect in SDS was found
      in patients with and without MDS. Patients showed a more prominent decrease in
      colony formation and increased apoptosis after preincubation with activating anti
      Fas antibody. Fas expression on marrow cells from patients was significantly
      higher than from normal controls. The difference between patients and controls
      for Fas expression was also significant for the following cell fraction
      subpopulations: CD34(-)/CD38(-), CD34(-)/CD38(+), and CD34(+). In conclusion, SDS
      hematopoietic progenitors are intrinsically flawed and have faulty proliferative
      properties and increased apoptosis. Bone marrow failure in SDS appears mediated
      by increased apoptosis as the central pathogenetic mechanism. This increased
      propensity for apoptosis is linked to increased expression of the Fas antigen and
      to hyperactivation of the Fas signaling pathway.

PMID- 11342426
TI  - Functional correction of FA-C cells with FANCC suppresses the expression of
      interferon gamma-inducible genes.
AB  - Because hematopoietic cells derived from Fanconi anemia (FA) patients of the C
      complementation group (FA-C) are hypersensitive to the inhibitory effects of
      interferon gamma (IFNgamma), the products of certain IFNgamma-inducible genes
      known to influence hematopoietic cell survival were quantified. High constitutive
      expression of the IFNgamma-inducible genes, IFN-stimulated gene factor 3 gamma
      subunit (ISGF3gamma), IFN regulatory factor-1 (IRF-1), and the cyclin-dependent
      kinase inhibitor p21(WAF1) was found in FANCC mutant B lymphoblasts, low-density
      bone marrow cells, and murine embryonic fibroblasts. Paradoxically, these cells
      do not activate signal transducer and activator of transcription (STAT) 1
      properly. In an attempt to clarify mechanisms by which FA-C cells overexpress
      IFNgamma-inducible genes in the face of defective STAT1 phosphorylation, it was
      reasoned that decreased levels of activated STAT1 might result in reduced
      expression of a hematopoietic IFNgamma-responsive protein that normally modulates
      expression of other IFNgamma-responsive genes. Levels of the IFNgamma-inducible
      factor IFN consensus sequence binding protein (ICSBP), a negative trans-acting
      regulator of some IFNgamma-inducible genes, were quantified. ICSBP levels were
      reduced in FA-C B lymphoblasts and MEFs. However, enforced expression of ICSBP
      failed to down-regulate IRF-1, ISGF3gamma, and p21(WAF1). Thus, the FANCC protein
      functions to modulate expression of a family of genes that in normal cells are
      inducible only by specific environmental cues for apoptosis or mitogenic
      inhibition, but it does so independently of the classic IFN-STAT1 pathway and is
      not the direct result of reduced ICSBP expression.

PMID- 11342427
TI  - Mimicry between neurokinin-1 and fibronectin may explain the transport and
      stability of increased substance P immunoreactivity in patients with bone marrow
      fibrosis.
AB  - Bone marrow (BM) fibrosis may occur in myeloproliferative diseases, lymphoma,
      myelodysplastic syndrome, myeloma, and infectious diseases. In this study, the
      role of substance P (SP), a peptide with pleiotropic functions, was examined.
      Some of its functions-angiogenesis, fibroblast proliferation, and stimulation of
      BM progenitors-are amenable to inducing BM fibrosis. Indeed, a significant
      increase was found in SP-immunoreactivity (SP-IR) in the sera of patients with BM
      fibrosis (n = 44) compared with the sera of patients with hematologic disorders
      and no histologic evidence of fibrosis (n = 46) (140 +/-12 vs 18 +/-3; P <.01).
      Immunoprecipitation of sera SP indicated that this peptide exists in the form of
      a complex with other molecule(s). It was, therefore, hypothesized that SP might
      be complexed with NK-1, its natural receptor, or with a molecule homologous to NK
      1. To address this, 3 cDNA libraries were screened that were constructed from
      pooled BM stroma or mononuclear cells with an NK-1 cDNA probe. A partial clone
      (clone 1) was retrieved that was 97% homologous to the ED-A region of fibronectin
      (FN). Furthermore, sequence analyses indicated that clone 1 shared significant
      homology with exon 5 of NK-1. Immunoprecipitation and Western blot analysis
      indicated co-migration of SP and FN in 27 of 31 patients with BM fibrosis.
      Computer-assisted molecular modeling suggested that similar secondary structural
      features between FN and NK-1 and the relative electrostatic charge might explain
      a complex formed between FN (negative) and SP (positive). This study suggests
      that SP may be implicated in the pathophysiology of myelofibrosis, though its
      role would have to be substantiated in future research. (Blood. 2001;97:3025
      3031)

PMID- 11342429
TI  - Accentuated response to phenylhydrazine and erythropoietin in mice genetically
      impaired for their GATA-1 expression (GATA-1(low) mice).
AB  - The response of mice genetically unable to up-regulate GATA-1 expression (GATA
      1(low) mice) to acute (phenylhydrazine [PHZ]-induced anemia) and chronic (in vivo
      treatment for 5 days with 10 U erythropoietin [EPO] per mouse) erythroid stimuli
      was investigated. Adult GATA-1(low) mice are profoundly thrombocytopenic
      (platelet counts [x 10(9)/L] 82.0 +/- 28.0 vs 840 +/- 170.0 of their control
      littermates, P <.001) but have a normal hematocrit (Hct) (approximately.47
      proportion of 1.0 [47%]). The spleens of these mutants are 2.5-fold larger than
      normal and contain 5-fold more megakaryocytic (4A5(+)), erythroid (TER-119(+)),
      and bipotent (erythroid/megakaryocytic, TER-119(+)/4A5(+)) precursor cells. Both
      the marrow and the spleen of these animals contain higher frequencies of burst
      forming units-erythroid (BFU-E)- and colony-forming units-erythroid (CFU-E)
      derived colonies (2-fold and 6-fold, respectively) than their normal littermates.
      The GATA-1(low) mice recover 2 days faster from the PHZ-induced anemia than their
      normal littermates (P <.01). In response to EPO, the Hct of the GATA-1(low) mice
      raised to.68 proportion of 1.0 (68%) vs the.55 proportion of 1.0 (55%) reached by
      the controls (P <.01). Both the GATA-1(low) and the normal mice respond to PHZ
      and EPO with similar (2- to 3-fold) increases in size and cellularity of the
      spleen (increases are limited mostly to cells, both progenitor and precursor, of
      the erythroid lineage). However, in spite of the similar relative cellular
      increases, the increases of all these cell populations are significantly higher,
      in absolute cell numbers, in the mutant than in the wild-type mice. In
      conclusion, the GATA-1(low) mutation increases the magnitude of the response to
      erythroid stimuli as a consequence of the expansion of the erythroid progenitor
      cells in their spleen.

PMID- 11342428
TI  - Inhibitory effect of the mi transcription factor encoded by the mutant mi allele
      on GA binding protein-mediated transcript expression in mouse mast cells.
AB  - The mi transcription factor (MITF) is a basic-helix-loop-helix leucine zipper
      (bHLH-Zip) transcription factor that is important for the development of mast
      cells. Mast cells of mi/mi genotype express normal amounts of abnormal MITF (mi
      MITF), whereas mast cells of tg/tg genotype do not express any MITFs. The
      synthesis of heparin is abnormal in the skin mast cells of mi/mi mice. Because N
      deacetylase/N-sulfotransferase 2 (NDST-2) is essential for the synthesis of
      heparin, the amount of NDST-2 messenger RNA (mRNA) was compared among cultured
      mast cells (CMCs) of +/+, mi/mi, and tg/tg genotypes. The NDST-2 mRNA was
      detected by in situ hybridization in the skin mast cells of +/+ and tg/tg mice,
      but not in the skin mast cells of mi/mi mice. The amount of NDST-2 mRNA decreased
      significantly in CMCs derived from mi/mi mice when compared to the values of +/+
      and tg/tg mice, suggesting that the defective form of MITF inhibited the
      expression of the NDST-2 transcript. The expression of NDST-2 transcript was
      mediated by the GGAA motif located in the 5'-untranslated region. GA binding
      protein (GABP) bound the GGAA motif and increased the amount of NDST-2
      transcript. The mi-MITF appeared to inhibit the ability of GABP to express NDST-2
      transcript by disturbing its nuclear localization. This is the first study to
      show that expression of an abnormal form of a bHLH-Zip transcription factor can
      dramatically alter the intracellular location of another DNA/RNA binding factor,
      which in turn brings about profound and unexpected consequences on transcript
      expression.

PMID- 11342430
TI  - A novel regulator of G-protein signaling bearing GAP activity for Galphai and
      Galphaq in megakaryocytes.
AB  - The regulator of G-protein signaling (RGS) negatively regulates the alpha subunit
      of G proteins by accelerating their intrinsic guanosine triphosphatase (GTPase)
      activity. Here are reported the isolation and characterization of a novel mouse
      RGS, termed RGS18, which is a new member of RGS subfamily B. Northern blot
      analysis showed that RGS18 messenger RNA was detected predominantly in spleen and
      hematopoietic cells, and immunohistochemical studies demonstrated that RGS18 was
      expressed in megakaryocytes, platelets, granulocytes/monocytes, and, weakly, in
      hematopoietic stem cells, but not in lymphocytes or erythrocytes. Although
      various subcellular localizations of RGS have been reported, RGS18 was found to
      be localized in cytoplasm in megakaryocytes. In vitro binding assays of RGS18
      with megakaryocyte cell lysates with or without AlF(4)(-) treatment demonstrated
      that RGS18 specifically binds to 2 alpha subunits of the G protein, Galphai and
      Galphaq. Furthermore, RGS18 clearly exhibited GTPase-activating protein (GAP)
      activity for Galphai and Galphaq but not for Galphas or Galpha12. In addition,
      chemokine stromal-derived factor 1 (SDF-1), which has been reported to stimulate
      megakaryocyte colony formation in the presence of thrombopoietin, affected the
      binding of RGS18 to Galphai but not to Galphaq. Therefore, the newly isolated
      RGS18 turned out to be a new member of the RGS family bearing GAP activity for
      Galphai, which might be stimulated by SDF-1 in megakaryocytes, as well as for
      Galphaq. Thus, RGS18 may play an important role in proliferation,
      differentiation, and/or migration of megakaryocytes.

PMID- 11342431
TI  - The relative quiescence of hematopoietic stem cells in nonhuman primates.
AB  - Quiescence has been thought to be required for the retention of the full
      biological potential of pluripotent hematopoietic stem cells (PHSCs). This
      hypothesis has been challenged recently by the observation that all murine PHSCs
      cycle continuously and constantly contribute to steady-state blood cell
      production. It was asked whether these observations could be extrapolated to
      describe hematopoiesis in higher mammals. In this series of experiments, the
      replicative history of PHSCs was examined in baboons by continuously
      administering bromodeoxyuridine (BrdU) for more than 85 weeks. The results
      indicate that under steady-state conditions, PHSCs remain largely quiescent but
      do cycle, albeit at a far lower rate than previously reported for rodent PHSCs.
      BrdU-labeled cycling PHSCs and progenitor cells were shown to have an extensive
      proliferative capacity and to contribute to blood cell production for prolonged
      periods of time. The proportion of PHSCs entering cell cycle could, however, be
      rapidly increased by the in vivo administration of granulocyte-colony stimulating
      factor. These data indicate that during steady-state hematopoiesis, baboon PHSCs
      require prolonged periods of time to cycle and that the proportion of PHSCs in
      cycle is not fixed but can be altered by external stimuli. The relative
      quiescence of PHSCs observed in this nonhuman primate model, in contrast to
      murine PHSCs, might explain the current barriers to genetic modification and ex
      vivo expansion of human PHSCs.

PMID- 11342432
TI  - Natural killer cell-dependent apoptosis of peripheral murine hematopoietic
      progenitor cells in response to Fas cross-linking: involvement of tumor necrosis
      factor-alpha.
AB  - Recently, a marked extramedullary myelopoiesis in Fas/CD95- or FasL/CD95L
      deficient mice has been reported. In the present in vitro study, the mechanisms
      underlying Fas-induced apoptosis of normal peripheral colony-forming unit-C (CFU
      C) progenitors in the spleen were analyzed. Surprisingly, it was found that
      clonogenic progenitors were protected from gammaIFN plus Fas-induced programmed
      cell death when Lin(+) cells were removed from cultured splenocytes. The cells
      that rendered CFU-C sensitive to the activation of the Fas pathway did not belong
      to the T or the myelocytic-monocytic lineage but comprised a non-B-cell subset
      expressing the activation marker B220. Among CD19(-) B220(+) splenocytes, nearly
      half were natural killer (NK) 1.1(+) cells whose in vivo depletion or deficiency
      in RAG2-gamma(c)(-/-) mice abrogated the effect of Fas cross-linking. NK cells
      exerted their accessory function, at least in part, through tumor necrosis factor
      alpha (TNF-alpha), which they readily produced during pretreatment with the anti
      Fas/CD95 monoclonal antibody and IFN-gamma and whose addition could compensate
      for the loss of sensitivity. In conclusion, this study provides evidence that
      peripheral clonogenic progenitors are not directly responsive to Fas cross
      linking, even in the presence of IFN-gamma, but require NK cells as a source of
      TNF-alpha to make them susceptible to this death pathway.

PMID- 11342433
TI  - Numerous growth factors, cytokines, and chemokines are secreted by human CD34(+)
      cells, myeloblasts, erythroblasts, and megakaryoblasts and regulate normal
      hematopoiesis in an autocrine/paracrine manner.
AB  - The aim of this study was to explore further the hypothesis that early stages of
      normal human hematopoiesis might be coregulated by autocrine/paracrine regulatory
      loops and by cross-talk among early hematopoietic cells. Highly purified normal
      human CD34(+) cells and ex vivo expanded early colony-forming unit-granulocyte
      macrophage (CFU-GM)-derived, burst forming unit-erythroid (BFU-E)-derived, and
      CFU-megakaryocyte (CFU-Meg)-derived cells were phenotyped for messenger RNA
      expression and protein secretion of various growth factors, cytokines, and
      chemokines to determine the biological significance of this secretion.
      Transcripts were found for numerous growth factors (kit ligand [KL], FLT3 ligand,
      fibroblast growth factor-2 [FGF-2], vascular endothelial growth factor [VEGF],
      hepatocyte growth factor [HGF], insulinlike growth factor-1 [IGF-1], and
      thrombopoietin [TPO]); cytokines (tumor necrosis factor-alpha, Fas ligand,
      interferon alpha, interleukin 1 [IL-1], and IL-16); and chemokines (macrophage
      inflammatory protein-1alpha [MIP-1alpha], MIP-1beta, regulated upon activation,
      normal T cell expressed and secreted [RANTES], monocyte chemotactic protein-3
      [MCP-3], MCP-4, IL-8, interferon-inducible protein-10, macrophage-derived
      chemokine [MDC], and platelet factor-4 [PF-4]) to be expressed by CD34(+) cells.
      More importantly, the regulatory proteins VEGF, HGF, FGF-2, KL, FLT3 ligand, TPO,
      IL-16, IGF-1, transforming growth factor-beta1 (TGF-beta1), TGF-beta2, RANTES,
      MIP-1alpha, MIP-1beta, IL-8, and PF-4 were identified in media conditioned by
      these cells. Moreover, media conditioned by CD34(+) cells were found to inhibit
      apoptosis and slightly stimulate the proliferation of other freshly isolated
      CD34(+) cells; chemo-attract CFU-GM- and CFU-Meg-derived cells as well as other
      CD34(+) cells; and, finally, stimulate the proliferation of human endothelial
      cells. It was also demonstrated that these various hematopoietic growth factors,
      cytokines, and chemokines are expressed and secreted by CFU-GM-, CFU-Meg-, and
      BFU-E-derived cells. It is concluded that normal human CD34(+) cells and
      hematopoietic precursors secrete numerous regulatory molecules that form the
      basis of intercellular cross-talk networks and regulate in an autocrine and/or a
      paracrine manner the various stages of normal human hematopoiesis.

PMID- 11342434
TI  - Depletion of circulating alpha(2)-antiplasmin by intravenous plasmin or
      immunoneutralization reduces focal cerebral ischemic injury in the absence of
      arterial recanalization.
AB  - In the absence of arterial recanalization, thrombolytic agents induce a dose
      related extension of focal cerebral ischemic injury (FII) in experimental
      animals. However, FII is smaller in mice lacking alpha(2)-antiplasmin (alpha(2)
      AP), the physiologic inhibitor of plasmin, suggesting its depletion might reduce
      FII in the absence of reperfusion. Therefore, the effect of human plasmin (Pli),
      human miniplasmin (mPli), and an Fab fragment neutralizing murine alpha(2)-AP
      (Fab-4H9) on FII after middle cerebral artery (MCA) ligation was studied in mice
      and in hamsters. In BALB/c mice, the median FII after 24 hours was 28 microL
      (range, 20-34) (n = 10) with saline and 23 microL (range, 17-26) (n = 9) with a
      single bolus of 0.07 mg Pli, given after MCA ligation (P =.010), which reduced
      alpha(2)-AP to 44% and fibrinogen from 0.75 to 0.44 g/L. FII was 20 microL
      (range, 13-26) (n = 6, P =.025) with 0.2 mg mPli and was 24 microL (range, 20-27)
      (n = 6, P =.020) with 1.7 mg Fab-4H9. Neuronal atrophy and reduction of laminin
      immunoreactivity were comparably observed in the infarct area after saline and
      Pli. In hamsters, a single bolus injection of 1 mg Pli, after MCA ligation,
      depleted alpha(2)-AP and fibrinogen and reduced FII at 24 hours from 20 microL
      (range, 9.9-38) (n = 6) to 7.0 microL (range, 0.44-31) (n = 7, P =.032). Thus,
      reduction of circulating alpha(2)-AP, with a single bolus of plasmin or of a
      neutralizing antibody fragment, significantly reduced FII after MCA ligation in
      mouse and hamster models, suggesting that, provided these observations can be
      extrapolated to human beings, transient depletion of circulating alpha(2)-AP
      might reduce ischemic stroke in the absence of reperfusion.

PMID- 11342435
TI  - Effect of the Pl(A2) alloantigen on the function of beta(3)-integrins in
      platelets.
AB  - The polymorphism responsible for the Pl(A2) alloantigen on the beta(3)-component
      of beta(3)-containing integrins is reported to be a risk factor for coronary
      thrombosis. This study examined the effect of Pl(A2) on the function of beta(3)
      integrins using platelets from subjects homozygous and heterozygous for Pl(A1)
      and Pl(A2). There was overlap in the distribution of the dissociation constant
      (K(d)) and maximum fibrinogen binding (B(max)) values for fibrinogen binding to
      alpha(IIb)beta(3) on platelets from Pl(A1) and Pl(A2) homozygotes and
      Pl(A1)/Pl(A2) heterozygotes. However, whereas there was no statistical difference
      in these values for the Pl(A1) homozygotes and Pl(A2) heterozygotes, the K(d) for
      the Pl(A2) homozygotes was significantly lower than that for the Pl(A1)/Pl(A2)
      heterozygotes, but was not statistically different from that for the Pl(A1)
      homozygotes. No differences were detected in ADP sensitivity between platelets
      from Pl(A1) homozygotes and Pl(A1)/Pl(A2) heterozygotes, in the IC(50) for RGDS
      inhibition of fibrinogen binding to alpha(IIb)beta(3), in the alpha(v)beta(3)
      mediated adhesion of platelets to osteopontin and vitronectin, and in the phorbol
      ester-stimulated adhesion to fibrinogen of B lymphocytes expressing
      alpha(IIb)beta(3) containing either the Pl(A1) or the Pl(A2) polymorphism.
      Finally, no differential effects of Pl(A2) on turbidometric platelet aggregation,
      platelet secretion, or platelet thrombus formation were found as measured in the
      PFA-100. Because no differences were detected in the ability of beta(3)-integrins
      to interact with ligands based on the presence or absence of the Pl(A2)
      polymorphism, the results suggest that factors unrelated to beta(3)-integrin
      function may account for the reported association of the Pl(A2) allele with
      coronary thrombosis.

PMID- 11342436
TI  - Platelet activation by Shiga toxin and circulatory factors as a pathogenetic
      mechanism in the hemolytic uremic syndrome.
AB  - Thrombocytopenia caused by platelet consumption in thrombi is a major
      manifestation of hemolytic uremic syndrome (HUS) associated with Shiga toxin
      (Stx) producing Escherichia coli. Platelets have glycosphingolipid receptors
      capable of binding Stx, but a direct interaction between the toxin and platelets,
      leading to platelet activation, has not been reported. In this study, it is shown
      that Stx1 and its B (binding) subunit (Stx1B), at 10 pg/mL to 10 ng/mL, bound to
      platelets. Toxin was internalized in platelets within 2 hours. This led to
      increased platelet aggregation, as demonstrated by confocal microscopy.
      Preincubation of Stx1B with anti-Stx1 antibody inhibited this reaction. Stx1
      induced morphologic changes in platelets seen on scanning electron microscopy. In
      the presence of platelets and tumor necrosis factor-pretreated human umbilical
      vein endothelial cells (HUVEC), Stx1 and Stx1B induced the binding of platelets
      to the endothelial cell membrane and were present at this binding site.
      Incubation of Stx1 and Stx1B with whole blood increased fibrinogen binding to
      platelets detected by flow cytometry. Fibrinogen binding was partially inhibited
      by preincubation with anti-Stx1. Stx1 increased platelet retention measured in a
      glass bead assay. In addition, plasma from 17 patients with HUS, taken during the
      acute phase of the disease, increased the retention of normal platelets and
      normalized after recovery. Taken together, the results of this investigation show
      that Stx1, Stx1B, and a factor or factors in the plasma of patients with HUS
      activate platelets. The presence of Stx1 at the binding site of platelets to
      HUVEC suggests that Stx may be directly involved in the prothrombotic state seen
      in HUS.

PMID- 11342438
TI  - Model for a factor IX activation complex on blood platelets: dimeric conformation
      of factor XIa is essential.
AB  - Human coagulation factor XI (FXI) is a plasma serine protease composed of 2
      identical 80-kd polypeptides connected by a disulfide bond. This dimeric
      structure is unique among blood coagulation enzymes. The hypothesis was tested
      that dimeric conformation is required for normal FXI function by generating a
      monomeric version of FXI (FXI/PKA4) and comparing it to wild-type FXI in assays
      requiring factor IX activation by activated FXI (FXIa). FXI/PKA4 was made by
      replacing the FXI A4 domain with the A4 domain from prekallikrein (PK). A dimeric
      version of FXI/PKA4 (FXI/PKA4-Gly326) was prepared as a control. Activated
      FXI/PKA4 and FXI/PKA4-Gly326 activate factor IX with kinetic parameters similar
      to those of FXIa. In kaolin-triggered plasma clotting assays containing purified
      phospholipid, FXI/PKA4 and FXI/PKA4-Gly326 have coagulant activity similar to
      FXI. The surface of activated platelets is likely to be a physiologic site for
      reactions involving FXI/FXIa. In competition binding assays FXI/PKA4, FXI/PKA4
      Gly326, and FXI have similar affinities for activated platelets (K(i) = 12-16
      nM). In clotting assays in which phospholipid is replaced by activated platelets,
      the dimeric proteins FXI and FXI/PKA4-Gly326 promote coagulation similarly;
      however, monomeric FXI/PKA4 has greatly reduced activity. Western immunoblot
      analysis confirmed that activated monomeric FXI/PKA4 activates factor IX poorly
      in the presence of activated platelets. These findings demonstrate the importance
      of the dimeric state to FXI activity and suggest a novel model for factor IX
      activation in which FXIa binds to activated platelets by one chain of the dimer,
      while binding to factor IX through the other.

PMID- 11342437
TI  - Gene induction by coagulation factor Xa is mediated by activation of protease
      activated receptor 1.
AB  - Cell signaling by coagulation factor Xa (Xa) contributes to pro-inflammatory
      responses in vivo. This study characterizes the signaling mechanism of Xa in a
      HeLa cell line that expresses protease-activated receptor 1 (PAR-1) but not PAR
      2, -3, or -4. Xa induced NF-kappaB in HeLa cells efficiently but with delayed
      kinetics compared to thrombin. This delay caused no difference in gene expression
      patterns, as determined by high-density microarray analysis. Both proteases
      prominently induced the angiogenesis-promoting gene Cyr61 and connective tissue
      growth factor. Inhibition of PAR-1 cleavage abolished MAP kinase phosphorylation
      and gene induction by Xa, demonstrating that Xa signals through PAR-1 and not
      through a novel member of the PAR family. Activation of cell surface prothrombin
      with the snake venom enzyme Ecarin also produced PAR-1-dependent signaling.
      However, though the response to Ecarin was completely blocked by the thrombin
      inhibitor hirudin, the response to Xa was not. This suggests that the Xa response
      is not mediated by locally generated thrombin. The concentration dependence of Xa
      for PAR-1 activation is consistent with previously characterized Xa-mediated PAR
      2 signaling, suggesting that local concentration of Xa on the cell surface,
      rather than sequence-specific recognition of the PAR scissile bond, determines
      receptor cleavage. This study demonstrates that PAR-1 cleavage by Xa can elicit
      the same cellular response as thrombin, but mechanistic differences in receptor
      recognition may be crucial for specific roles for Xa in signaling during spatial
      or temporal separation from thrombin generation.

PMID- 11342439
TI  - Proteolysis of the urokinase-type plasminogen activator receptor by
      metalloproteinase-12: implication for angiogenesis in fibrin matrices.
AB  - Pericellular proteolysis plays an important role in cell migration and the
      formation of new capillary structures. The plasminogen activator/plasmin and
      matrix degrading metalloproteinase (MMP) cascades act together in the remodeling
      of matrix and cell-matrix contacts. Previously we have shown that the formation
      of capillary structures by human foreskin microvascular endothelial cells
      (hMVECs) in a 3-dimensional fibrin matrix requires a functional urokinase-type
      plasminogen activator receptor (u-PAR). Here we report on the unexpected finding
      that inhibition of hMVEC-derived MMP activity by BB94 (batimastat) increased the
      outgrowth of capillary structures in a fibrin matrix. BB94 prevented the release
      of the u-PA binding domain D1 of u-PAR and thereby increased the number of
      functional u-PARs on hMVECs without affecting the u-PAR messenger RNA levels.
      Comparison of various types of protease inhibitors pointed to the prime
      involvement of MMP activity. Using recombinant MMPs it was shown that MMP-12
      activity was able to release the D1 domain of cellularly expressed u-PAR. In
      addition, the expression of MMP-12 in control and basic fibroblast growth
      factor/tumor necrosis factor-alpha-stimulated hMVECs was shown by reverse
      transcriptase-polymerase chain reaction, suggesting that endothelial cell-derived
      MMP-12 may be involved in angiogenesis-related u-PAR shedding. This new mechanism
      of u-PAR cleavage provides new insights into the mutual interactions between the
      MMP and u-PA/plasmin systems. Moreover, it may be helpful in the interpretation
      of recent data on the use of specific MMP inhibitors in the treatment of several
      types of cancer.

PMID- 11342440
TI  - Augmentation of antitumor effects by NK cell inhibitory receptor blockade in
      vitro and in vivo.
AB  - Subsets of natural killer (NK) cells are characterized by the expression of
      inhibitory and/or stimulatory receptors specific for major histocompatibility
      complex (MHC) class I determinants. In mice, these include the Ly49 family of
      molecules. One mechanism by which tumor cells may evade NK cell killing is by
      expressing the appropriate MHC class I and binding inhibitory Ly49 receptors.
      Therefore, the question of whether blocking the interaction between the Ly49
      inhibitory receptors on NK and MHC class I cells on tumor cells augments
      antitumor activity was investigated. Blockade of Ly49C and I inhibitory receptors
      using F(ab')(2) fragments of the 5E6 monoclonal antibody (mAb) resulted in
      increased cytotoxicity against syngeneic tumors and decreased tumor cell growth
      in vitro. The effect of 5E6 F(ab')(2) was specific for the MHC of the tumor, as
      the use of F(ab')(2) of the mAb against Ly49G2 failed to increase NK activity.
      Treatment of leukemia-bearing mice with 5E6 F(ab')(2) fragments or adoptive
      transfer of NK cells treated ex vivo with the F(ab')(2) resulted in significant
      increases in survival. These results demonstrate that blockade of NK inhibitory
      receptors enhances antitumor activity both in vitro and in vivo, suggesting that
      NK inhibitory receptors can be responsible for diminishing antitumor responses.
      Therefore, strategies to block inhibitory receptors may be of potential use in
      increasing the efficacy of immunotherapy. (Blood. 2001;97:3132-3137)

PMID- 11342441
TI  - Targeting of a B7-1 (CD80) immunoglobulin G fusion protein to acute myeloid
      leukemia blasts increases their costimulatory activity for autologous remission T
      cells.
AB  - Transfection of tumor cells with the gene encoding the costimulatory molecule B7
      1 (CD80), the ligand for CD28 and cytotoxic T lymphocye antigen-4 on T cells, has
      been shown to result in potent T-cell-mediated antitumor immunity. As an
      alternative approach, this study analyzed the costimulatory capacity of a human
      B7-1 immunoglobulin G (IgG) fusion protein targeted to the cell membrane of human
      acute myeloid leukemia (AML) blasts. Flow cytometric analysis revealed a low
      constitutive expression of B7-1 on human AML blasts (on average, 3.0 +/- 4.3%; n
      = 50). In contrast, the expression of B7-2 (CD86) was highly heterogeneous and
      higher in AML blasts of French-American-British classification types M4 and M5 (P
      <.0001). The B7-1 IgG fusion protein used in this study efficiently costimulated
      the proliferation of resting and preactivated T cells when immobilized on
      plastic. After preincubation with B7-1 IgG, specific binding of the fusion
      protein to the high-affinity Fcgammareceptor I (CD64) on leukemic cells was
      demonstrated and was found to increase the proliferation of both allogeneic and
      autologous T cells in costimulation experiments. Furthermore, targeting of B7-1
      IgG to the tumor membrane resulted in increased proliferation of autologous
      remission T cells and had the potential to generate an enhanced redirected
      cytotoxic T-cell response against autologous AML blasts. In summary, the
      targeting of B7-1 IgG fusion protein described in this study represents a
      strategy alternative to gene therapy to restore the expression of the
      costimulatory molecule B7-1 on human AML blasts, thereby enhancing their
      immunogenicity for autologous T cells. This new approach may have implications
      for T-cell-mediated immunotherapy in AML.

PMID- 11342442
TI  - Human natural killer cells: a unique innate immunoregulatory role for the
      CD56(bright) subset.
AB  - During the innate immune response to infection, monocyte-derived cytokines
      (monokines), stimulate natural killer (NK) cells to produce immunoregulatory
      cytokines that are important to the host's early defense. Human NK cell subsets
      can be distinguished by CD56 surface density expression (ie, CD56(bright) and
      CD56(dim)). In this report, it is shown that CD56(bright) NK cells produce
      significantly greater levels of interferon-gamma, tumor necrosis factor-beta,
      granulocyte macrophage-colony-stimulating factor, IL-10, and IL-13 protein in
      response to monokine stimulation than do CD56(dim) NK cells, which produce
      negligible amounts of these cytokines. Further, qualitative differences in
      CD56(bright) NK-derived cytokines are shown to be dependent on the specific
      monokines present. For example, the monokine IL-15 appears to be required for
      type 2 cytokine production by CD56(bright) NK cells. It is proposed that human
      CD56(bright) NK cells have a unique functional role in the innate immune response
      as the primary source of NK cell-derived immunoregulatory cytokines, regulated in
      part by differential monokine production.

PMID- 11342443
TI  - Red blood cells inhibit activation-induced cell death and oxidative stress in
      human peripheral blood T lymphocytes.
AB  - Red blood cells (RBCs) are known to perform one prominent function: to carry and
      deliver oxygen to the tissues. Earlier studies, however, suggested a role for
      RBCs in potentiating T-cell proliferation in vitro. Here it is shown that the
      presence of RBCs in cultures of stimulated human peripheral blood lymphocytes
      strengthens T-cell proliferation and survival. Analysis of phosphatidylserine
      externalization and DNA fragmentation showed that RBCs inhibit T-cell apoptosis.
      This inhibition correlated with a reduction in CD71 but not CD95 expression. RBCs
      enhanced T-cell proliferation and survival upon activation with
      phytohemagglutinin and with OKT3 antibodies. Studies aimed at characterizing the
      cellular and molecular basis of the protection afforded to T cells by RBCs showed
      that (1) optimal protection required intact RBCs and red cell/T-cell contact but
      not monocytes; (2) RBCs markedly reduced the level of intracellular reactive
      oxygen species; and (3) RBCs inhibited the formation of protein-bound acrolein, a
      peroxidation adduct in biologic systems. Overall, these data indicate that human
      RBCs protect T cells from activation-induced cell death, at least in part by
      reducing the pro-oxidant state, and suggest a role for RBCs as conceivable
      modulators of T-cell homeostasis.

PMID- 11342444
TI  - Increases in circulating and lymphoid tissue interleukin-10 in autoimmune
      lymphoproliferative syndrome are associated with disease expression.
AB  - Autoimmune lymphoproliferative syndrome (ALPS) is an inherited disorder in which
      genetic defects in proteins that mediate lymphocyte apoptosis, most often Fas,
      are associated with enlargement of lymph nodes and the spleen and a variety of
      autoimmune manifestations. Some patients with ALPS have relatives with these same
      apoptotic defects, however, who are clinically well. This study showed that the
      circulating levels of interleukin 10 (IL-10) were significantly higher (P <.001)
      in 21 patients with ALPS than in healthy controls. Moreover, the peripheral blood
      mononuclear cells (PBMCs) and lymphoid tissues of these patients with ALPS
      contained significantly higher levels of IL-10 messenger RNA (mRNA; P <.001 and P
      <.01, respectively). By fractionating PBMC populations, disproportionately high
      concentrations of IL-10 mRNA were found in the CD4(-)CD8(-) T-cell population,
      expansion of which is virtually pathognomonic for ALPS. Immunohistochemical
      staining showed intense IL-10 protein signals in lymph node regions known to
      contain CD4(-)CD8(-) T cells. Nonetheless, in vitro studies showed no influence
      of IL-10 on the survival of CD4(-)CD8(-) T cells. Overexpression of IL-10 in
      patients with inherited apoptotic defects is strongly associated with the overt
      manifestations of ALPS.

PMID- 11342445
TI  - Impaired dendritic cell maturation in patients with chronic, but not resolved,
      hepatitis C virus infection.
AB  - Dendritic cells (DCs) are important for the initiation of immune responses to
      foreign antigens. Their antigen uptake and presentation capacities enable them to
      prime and activate T cells. Immature DCs capture antigens; however, they must be
      activated to mature before serving as efficient antigen-presenting cells. The
      antigen-presenting capacity of DCs can be diminished during viral infection and
      as a consequence of tumor formation. Chronic infection with hepatitis C virus
      (HCV) has been shown to affect the allostimulatory function of DCs. In this
      study, it is demonstrated that monocyte-derived DCs from patients with chronic
      HCV infection do not respond to maturation stimuli. Instead, they maintain their
      immature phenotype, reflected by the pattern of cell surface markers and by their
      continued capacity to uptake antigen. Moreover, their allostimulatory abilities
      are impaired compared with those of mature DCs derived from healthy donors. To
      investigate a possible correlation between viral clearance and this DC maturation
      defect, patients with resolved HCV infection after a course of antiviral therapy
      were studied. Results demonstrate that DCs from patients who cleared HCV behaved
      like DCs from healthy donors: in response to maturation stimuli, they decrease
      antigen uptake, up-regulate expression of appropriate surface markers, and are
      potent stimulators of allogeneic T cells. (Blood. 2001;97:3171-3176)

PMID- 11342446
TI  - Impaired production of naive T lymphocytes in human T-cell leukemia virus type I
      infected individuals: its implications in the immunodeficient state.
AB  - Opportunistic infections frequently occur in patients with adult T-cell leukemia
      (ATL) and human T-cell leukemia virus type I (HTLV-I) carriers. However, the
      underlying mechanisms of such infections remain unknown. To clarify the mechanism
      of immunodeficiency in those infected with HTLV-I, this study analyzed the T-cell
      subsets in HTLV-I carriers and patients with HTLV-I-associated
      myelopathy/tropical spastic paraparesis and ATL using 3-color fluorescence with
      CD62L and CD45RA coexpression either with CD4(+) or CD8(+) T cells. The number of
      naive T lymphocytes was markedly suppressed in patients with ATL, particularly in
      those with acute form, compared with uninfected control individuals. The number
      of naive T cells was low in HTLV-I-infected individuals under 50 years old
      compared with uninfected individuals, whereas the number of memory T lymphocytes
      was greater in HTLV-I-infected individuals. Although the increase of memory T
      lymphocytes correlated with HTLV-I provirus loads, no relationship was found
      between naive T-cell counts and provirus loads. T-cell receptor rearrangement
      excision circles (TRECs), which are generated by DNA recombination during early T
      lymphopoiesis, were quantified to evaluate thymic function in HTLV-I-infected
      individuals. TREC levels were lower in HTLV-I-infected individuals than in
      uninfected individuals. In HTLV-I carriers less than 70 years old, an increase of
      Epstein-Barr virus DNA in peripheral blood mononuclear cells was observed in 6 of
      16 (38%) examined, whereas it was detectable in only 1 of 11 uninfected controls.
      These results suggested that the low number of naive T lymphocytes was due to
      suppressed production of T lymphocytes in the thymus, which might account for
      immunodeficiency observed in HTLV-I-infected individuals.

PMID- 11342448
TI  - Defective octamer-dependent transcription is responsible for silenced
      immunoglobulin transcription in Reed-Sternberg cells.
AB  - The absence of immunoglobulin (Ig) expression in B-cell-derived Hodgkin and Reed
      Sternberg (HRS) cells of classical Hodgkin disease (cHD) was initially suggested
      to be caused by crippling mutations in the Ig promoter or coding region. More
      recent investigations have, however, challenged this concept. This study
      addressed the role of mutations in the Ig promoter region in HRS cells. Nine
      cases of cHD and 3 B-cell-derived HD lines were analyzed for mutations in the
      TATA box and octamer motif of the Ig promoter. Mutations in the octamer motif
      were found in only 1 of the 9 cases and in 1 of the 3 HD cell lines (L1236).
      Furthermore, in all cases either a complete lack or strong reduction in the
      expression of the Oct2 transcription factor and the BOB.1/OBF.1 coactivator were
      found. The relevance of the rare promoter mutations was investigated by assaying
      the activity of Ig promoter reporter constructs transfected into the HD cell line
      L1236, which harbors a mutated octamer motif. These Ig reporter constructs were
      completely inactive in L1236 cells; however, their activity could be
      reconstituted by the cotransfection of a BOB.1/OBF.1 expression vector. The
      additional transfection with an Oct2 expression vector did not further enhance
      the Ig promoter activity. The conclusions drawn from these results are that
      crippling mutations in the Ig promoter and coding region are not the sole cause
      for the lack of Ig expression in HRS cells and that defects in the transcription
      machinery such as absence of BOB.1/OBF.1 are more important for this phenomenon.

PMID- 11342447
TI  - Truncated thioredoxin (Trx80) induces production of interleukin-12 and enhances
      CD14 expression in human monocytes.
AB  - Human thioredoxin (Trx) is the major 12-kd cellular disulfide-reductase that on
      secretion acts as a cocytokine with several interleukins. Truncated Trx with the
      80 N-terminal residues (Trx80), also present in plasma, was by itself a mitogenic
      cytokine for human peripheral blood mononuclear cells (PBMC). This study
      investigated which cells in PBMC are targets of recombinant Trx80. Purified human
      CD14(+) monocytes, but not B or T cells, in a synthetic medium were activated to
      differentiation by Trx80 as measured by flow cytometry of surface antigens
      because exposure to 100 nM Trx80 increased expression of CD14, CD40, CD54, and
      CD86. Proliferation of the monocytes was increased in a dose-dependent manner by
      Trx80 in concentrations ranging from 10 nM to 1 microM. Trx or interleukin (IL) 2
      did not induce proliferation or expression of surface antigens on monocytes.
      Trx80 alone induced secretion of IL-12 from CD40(+) monocytes in the PBMC
      cultures and this effect was enhanced by IL-2. Trx80 and IL-2 together were
      strongly synergistic to induce secretion of interferon-gamma in PBMC cultures.
      The results showed that Trx80 is a potent cytokine for normal human monocytes and
      directs the immune system in favor of a Th1 response via IL-12 production.

PMID- 11342449
TI  - Targeting of the CD33-calicheamicin immunoconjugate Mylotarg (CMA-676) in acute
      myeloid leukemia: in vivo and in vitro saturation and internalization by leukemic
      and normal myeloid cells.
AB  - Antibody-targeted chemotherapy is a promising therapy in patients with acute
      myeloid leukemia (AML). In a phase II study of Mylotarg (CMA-676, gemtuzumab
      ozogamicin), which consists of a CD33 antibody linked to calicheamicin,
      saturation and internalization by leukemic and normal myeloid cells were analyzed
      in 122 patients with relapsed AML. Peripheral blood samples were obtained just
      before and 3 and 6 hours after the start of the first and second Mylotarg
      treatment cycles. Within 3 to 6 hours after infusion, near complete saturation of
      CD33 antigenic sites by Mylotarg was reached for AML blasts, monocytes, and
      granulocytes, whereas Mylotarg did not bind to lymphocytes. Saturation levels
      prior to the start of the second Mylotarg treatment cycle were significantly
      increased compared with background levels before the start of the first cycle.
      This apparently was caused by remaining circulating Mylotarg from the first
      treatment cycle (approximately 2 weeks earlier). On binding of Mylotarg to the
      CD33 antigen, Mylotarg was rapidly internalized, as determined by the decrease in
      maximal surface membrane Mylotarg binding. Internalization of Mylotarg was also
      demonstrated in myeloid cells in vitro and was confirmed by confocal laser
      microscopy. In vitro studies using pulse labeling with Mylotarg showed a
      continuous renewed membrane expression of CD33 antigens, which can significantly
      increase the internalization process and thereby the intracellular accumulation
      of the drug. Finally, Mylotarg induced dose-dependent apoptosis in myeloid cells
      in vitro. These data indicate that Mylotarg is rapidly and specifically targeted
      to CD33(+) cells, followed by internalization and subsequent induction of cell
      death.

PMID- 11342450
TI  - Association between polymorphisms of folate- and methionine-metabolizing enzymes
      and susceptibility to malignant lymphoma.
AB  - Genetic alteration is considered a probable cause of malignant lymphoma. Folate
      and methionine metabolism play essential roles in DNA synthesis and DNA
      methylation, and their metabolic pathways might thus affect disease
      susceptibility. In the present study, 2 polymorphisms were evaluated for a folate
      metabolic enzyme, methylenetetrahydrofolate reductase (MTHFR), and one was
      evaluated for methionine synthase (MS). The 2 polymorphisms, MTHFR677 C-->T and
      MTHFR1298 A-->C, are reported to reduce the enzyme activity, which causes
      intracellular accumulation of 5,10-methylenetetrahydrofolate and results in a
      reduced incidence of DNA double-strand breakage. The MS2756 A-->G polymorphism
      also reduces the enzyme activity and results in the hypomethylation of DNA. To
      evaluate the association between malignant lymphoma susceptibility and these
      polymorphisms, hospital-based case-control study was conducted in Aichi Cancer
      Center. Ninety-eight patients with histologically confirmed lymphoma and 243
      control subjects without cancer were evaluated. Unconditional logistic regression
      analyses revealed a higher susceptibility with the MTHFR677 CC and the MTHFR1298
      AA genotypes (odds ratio, 2.26; 95% confidence interval, 1.26-4.02) when those
      harboring at least one variant allele in either polymorphism of MTHFR were
      defined as the reference. For the MS polymorphism, the MS2756 GG genotype also
      showed a higher susceptibility (odds ratio, 3.83; 95% CI, 1.21-12.1) than those
      with MS2756 AA or AG types. The significance was not altered when these 3
      polymorphisms were evaluated in combination, and the results suggest that folate
      and methionine metabolism play important roles in the occurrence of malignant
      lymphomas. Further studies to confirm the association and detailed biologic
      mechanisms are now required.

PMID- 11342452
TI  - Preconditioning with fetal cord blood facilitates engraftment of primary
      childhood T-cell acute lymphoblastic leukemia in immunodeficient mice.
AB  - Childhood T-cell acute lymphoblastic leukemia (T-ALL) is one of the most common
      childhood cancers. It is reported that preconditioning sublethally irradiated
      immunodeficient NOD/SCID (nonobese diabetic/X-linked severe combined
      immunodeficient) mice with human cord blood mononuclear cells facilitates the
      engraftment, expansion, and dissemination in these mice of primary T-ALL cells
      obtained from patients at the time of diagnosis. Cells recovered from mouse bone
      marrow or spleen resembled the original leukemia cells from patients with respect
      to surface lineage markers and T-cell receptor Vbeta gene rearrangements.
      Moreover, the pattern of leukemia dissemination in mouse tissues, resulting in
      universally fatal leukemia, is reminiscent of the human clinical disease. In
      addition, the fidelity of the model to the human disease is documented with
      regard to the presence of morphologically identifiable human leukemia cells in
      mouse bone marrow and blood and the maintenance of leukemia-initiating capacity
      within the leukemia-engrafted mouse. Therefore, several lines of independent
      approaches are used to suggest that the engrafted cells are of human leukemia
      origin and are not derived from cord blood. The in vivo model described here
      should enable the study of the growth properties of primary T-ALL cells obtained
      from patients and should prove useful in evaluating the potential efficacy of
      therapeutic strategies directed toward T-ALL.

PMID- 11342453
TI  - Novel methylation targets in de novo acute myeloid leukemia with prevalence of
      chromosome 11 loci.
AB  - Aberrant DNA methylation is believed to be important in tumorigenesis by causing
      either transcriptional inactivation of genes or chromosomal instability. Several
      laboratories have identified promoter hypermethylation of tumor suppressor genes
      in acute myeloid leukemia (AML). However, these studies do not provide a global
      assessment of overall methylation changes and do not allow the identification of
      novel methylated sequences. Previously, nonrandom CpG island methylation was
      reported in 17 adult de novo AML diagnostic samples when compared with the
      corresponding remission samples by means of restriction landmark genomic scanning
      (RLGS). That study has been expanded on by an analysis of a larger set of CpG
      islands (1740 vs 1184), which now provides details of 33 cloned methylated loci,
      including 21 known genes or expressed sequence tags. Five of these cloned loci
      appear to be methylated only in AML and not in the 6 solid tumors studied in this
      study (more than 98 samples analyzed). Chromosomal location was available for 30
      of the 33 loci, and 5 of these 30 (17%) are localized to chromosome 11,
      suggesting a trend toward overrepresentation of methylation events on this
      chromosome. These results provide evidence for widespread aberrant methylation in
      AML, with identification of novel methylation targets, epigenetic changes that
      appear unique to AML, and apparent preferential methylation on chromosome 11.

PMID- 11342451
TI  - Identification of a leukemic counterpart of the plasmacytoid dendritic cells.
AB  - This work aims to demonstrate that CD4(+)CD56(+) malignancies arise from
      transformed cells of the lymphoid-related plasmacytoid dendritic cell (pDC)
      subset. The analysis of malignant cells from 7 patients shows that in all cases,
      like pDCs, leukemic cells are negative for lineage markers CD3, CD19, CD13, CD33,
      and CD11c but express high levels of interleukin-3 receptor alpha chain (IL
      3Ralpha), HLA-DR, and CD45RA. Tumor cells produce interferon-alpha in response to
      influenza virus, while upon maturation with IL-3 they become a powerful inducer
      of naive CD4(+) T-cell proliferation and promote their T-helper 2 polarization.
      As pDCs, leukemic cells also express pre-Talpha and lambda-like 14.1 transcripts,
      arguing in favor of a lymphoid origin. In addition, malignant cells express
      significant levels of CD56 and granzyme B. Overall, those observations suggest
      that CD4(+)CD56(+) leukemic cells could represent the malignant counterpart of
      pDCs, both of which are closely related to B, T, and NK cells.

PMID- 11342454
TI  - Tyrosine kinase inhibitor STI571 potentiates the pharmacologic activity of
      retinoic acid in acute promyelocytic leukemia cells: effects on the degradation
      of RARalpha and PML-RARalpha.
AB  - The 2-phenylaminopyrimidine derivative STI571 is a selective inhibitor of c-Abl,
      c-kit, and platelet-derived growth factor-receptor tyrosine kinases and is
      presently in phase II-III clinical studies. Here, this study reports on a novel
      pharmacologic activity of the compound, ie, enhancement of the cyto
      differentiating, growth-inhibitory, and apoptogenic actions of all-trans-retinoic
      acid (ATRA). Whereas STI571 is not a cytodifferentiating agent by itself, the
      compound interacts with ATRA and enhances the myeloid maturation program set in
      motion by the retinoid in the PML-RARalpha(+) acute promyelocytic leukemia NB4
      and the PML-RARalpha(-) myeloblastic HL60 and U937 cell lines. In addition,
      STI571 relieves the cyto-differentiation block observed in the ATRA-resistant
      cell lines, NB4.R1, NB4.306, and NB4.007. In NB4 promyelocytes, a RARalpha
      agonist, but not an RXR agonist, can substitute for ATRA and interact with
      STI571. By contrast, STI571 is unique among c-Abl-specific tyrosine kinase
      inhibitors in modulating the pharmacologic activity of ATRA. In NB4 cells,
      enhanced cyto-differentiation results in increased up-regulation of the
      expression of a number of genes coding for myeloid differentiation markers,
      including CD11b, CD11c, and some of the components of the nicotinamide adenine
      dinucleotide phosphate-oxidase enzymatic complex. All this is accompanied by
      inhibition of c-Abl tyrosine phosphorylation and retardation of the retinoid
      dependent degradation of PML-RARalpha and RARalpha. Stabilization of the 2
      retinoic acid receptors is likely to be the result of augmented and accelerated
      inhibition of the proteasome-dependent proteolytic activity observed on ATRA
      treatment.

PMID- 11342455
TI  - Hypoxia induces lytic replication of Kaposi sarcoma-associated herpesvirus.
AB  - There is substantial evidence that Kaposi sarcoma-associated herpesvirus (KSHV)
      plays an important role in the pathogenesis of all forms of Kaposi sarcoma (KS).
      It has been noted that KS commonly occurs in locations, such as the feet, where
      tissue may be poorly oxygenated. On the basis of this observation, the potential
      role of hypoxia in the reactivation of KSHV replication was explored by studying
      2 KSHV-infected primary effusion lymphoma B-cell lines (BC-3 and BCBL-1) latently
      infected with KSHV. Acute and chronic exposure of these cells to hypoxia (1%
      O(2)) induced KSHV lytic replication, as indicated by an increase in
      intracellular lytic protein expression and detection of virus in cell
      supernatants by Western immunoblotting. In addition, hypoxia increased the levels
      of secreted viral interleukin-6. Moreover, hypoxia enhanced the lytic replication
      initiated by the viral inducer 12-O-tetradecanoylphorbol-13-acetate.
      Desferoxamine and cobalt chloride, 2 compounds that increase the intracellular
      levels of hypoxia-inducible factor 1, were also able to induce KSHV lytic
      replication. These studies suggest that hypoxia is an inducer of KSHV
      replication. This process may play an important role in the pathogenesis of KS.

PMID- 11342456
TI  - Phosphoinositide 3-kinase modulation of beta(3)-integrin represents an endogenous
      "braking" mechanism during neutrophil transmatrix migration.
AB  - During episodes of inflammation, neutrophils (polymorphonuclear leukocytes
      [PMNs]) encounter subendothelial matrix substrates that may require additional
      signaling pathways as directives for movement through the extracellular space.
      Using an in vitro endothelial and epithelial model, inhibitors of
      phosphoinositide 3-kinase (PI3K) were observed to promote chemoattractant
      stimulated migration by as much as 8 +/- 0.3-fold. Subsequent studies indicated
      that PMNs respond in a similar manner to RGD-containing matrix substrates and
      that PMN-matrix interactions are potently inhibited by antibodies directed
      against beta(3)- but not beta(1)-integrin antibodies, and that PI3K inhibitors
      block beta(3)-integrin dependence. Biochemical analysis of intracellular beta(3)
      integrin uncoupling by PI3K inhibitors revealed diminished beta(3)-integrin
      tyrosine phosphorylation and decreased association with p72(syk). Similarly, the
      p72(syk) inhibitor piceatannol promoted PMN transmatrix migration, whereas HIV
      tat peptide-facilitated loading of peptides corresponding to the beta(3)-integrin
      cytoplasmic tail identified the functional tyrosine residues for this activity.
      These data indicate that PI3K-regulated beta(3)-integrin represents a natural
      "braking" mechanism for PMNs during transit through the extracellular matrix.

PMID- 11342457
TI  - Short-chain fatty acid derivatives stimulate cell proliferation and induce STAT-5
      activation.
AB  - Current chemotherapeutic and butyrate therapeutics that induce fetal hemoglobin
      expression generally also suppress erythropoiesis, limiting the production of
      cells containing fetal hemoglobin (F cells). Recently, selected short-chain fatty
      acid derivatives (SCFADs) were identified that induce endogenous gamma-globin
      expression in K562 cells and human burst-forming units-erythroid and that
      increase proliferation of human erythroid progenitors and a multilineage
      interleukin-3-dependent hematopoietic cell line. In this report, gamma-globin
      inducibility by these SCFADs was further demonstrated in mice transgenic for the
      locus control region and the entire beta-globin gene locus in a yeast artificial
      chromosome and in 2 globin promoter-reporter assays. Conditioned media
      experiments strongly suggest that their proliferative activity is a direct effect
      of the test compounds. Investigation of potential mechanisms of action of these
      SCFADs demonstrates that these compounds induce prolonged expression of the
      growth-promoting genes c-myb and c-myc. Both butyrate and specific growth
      stimulatory SCFADs induced prolonged signal transducer and activator of
      transcription (STAT)-5 phosphorylation and activation, and c-cis expression,
      persisting for more than 120 minutes, whereas with IL-3 alone phosphorylation
      disappeared within minutes. In contrast to butyrate treatment, the growth
      stimulating SCFADs did not result in bulk histone H4 hyperacetylation or
      induction of p21(Waf/Cip), which mediates the suppression of cellular growth by
      butyrate. These findings suggest that the absence of bulk histone
      hyperacetylation and p21 induction, but prolonged induction of cis, myb, myc, and
      STAT-5 activation, contribute to the cellular proliferation induced by selected
      SCFADs.

PMID- 11342458
TI  - Modifications in the CD36 binding domain of the Plasmodium falciparum variant
      antigen are responsible for the inability of chondroitin sulfate A adherent
      parasites to bind CD36.
AB  - Adhesion of mature Plasmodium falciparum parasitized erythrocytes to
      microvascular endothelial cells or to placenta contributes directly to the
      virulence and severe pathology of P falciparum malaria. Whereas CD36 is the major
      endothelial receptor for microvasculature sequestration, infected erythrocytes
      adhering in the placenta bind chondroitin sulfate A (CSA) but not CD36. Binding
      to both receptors is mediated by different members of the large and diverse
      protein family P falciparum erythrocyte membrane protein-1 (PfEMP-1) and involves
      different regions of the molecule. The PfEMP-1-binding domain for CD36 resides in
      the cysteine-rich interdomain region 1 (CIDR-1). To explore why CSA-binding
      parasites do not bind CD36, CIDR-1 domains from CD36- or CSA-binding parasites
      were expressed in mammalian cells and tested for adhesion. Although CIDR-1
      domains from CD36-adherent strains strongly bound CD36, those from CSA-adherent
      parasites did not. The CIDR-1 domain has also been reported to bind CSA. However,
      none of the CIDR-1 domains tested bound CSA. Chimeric proteins between CIDR-1
      domains that bind or do not bind CD36 and mutagenesis experiments revealed that
      modifications in the minimal CD36-binding region (M2 region) are responsible for
      the inability of CSA-selected parasites to bind CD36. One of these modifications,
      mapped to a 3-amino acid substitution in the M2 region, ablated binding in one
      variant and largely reduced binding of another. These findings provide a
      molecular explanation for the inability of placental sequestered parasites to
      bind CD36 and provide additional insight into critical residues for the CIDR
      1/CD36 interaction.

PMID- 11342459
TI  - Functional requirements for phenotypic correction of murine beta-thalassemia:
      implications for human gene therapy.
AB  - As initial human gene therapy trials for beta-thalassemia are contemplated, 2
      critical questions important to trial design and planning have emerged. First,
      what proportion of genetically corrected hematopoietic stem cells (HSCs) will be
      needed to achieve a therapeutic benefit? Second, what level of expression of a
      transferred globin gene will be required to improve beta-thalassemic
      erythropoiesis? These questions were directly addressed by means of a murine
      model of severe beta-thalassemia. Generation of beta-thalassemic mice chimeric
      for a minority proportion of genetically normal HSCs demonstrated that normal HSC
      chimerism levels as low as 10% to 20% resulted in significant increases in
      hemoglobin (Hb) level and diminished extramedullary erythropoiesis. A large
      majority of the peripheral red cells in these mice were derived from the small
      minority of normal HSCs. In a separate set of independent experiments, beta
      thalassemic mice were bred with transgenic mice that expressed different levels
      of human globins. Human gamma-globin messenger RNA (mRNA) expression at 7% of the
      level of total endogenous alpha-globin mRNA in thalassemic erythroid cells
      resulted in improved red cell morphology, a greater than 2-g/dL increase in Hb,
      and diminished reticulocytosis and extramedullary erythropoiesis. Furthermore,
      gamma-globin mRNA expression at 13% resulted in a 3-g/dL increase in Hb and
      nearly complete correction of red cell morphology and other indices of
      inefficient erythropoiesis. These data indicate that a significant therapeutic
      benefit could be achieved with expression of a transferred globin gene at about
      15% of the level of total alpha-globin mRNA in patients with severe beta
      thalassemia in whom 20% of erythroid precursors express the vector genome.

PMID- 11342461
TI  - Intra-bone marrow injection of allogeneic bone marrow cells: a powerful new
      strategy for treatment of intractable autoimmune diseases in MRL/lpr mice.
AB  - Intractable autoimmune diseases in chimeric resistant MRL/lpr mice were treated
      by a new bone marrow transplantation (BMT) method consisting of fractionated
      irradiation, 5.5 Gy x 2, followed by intra-bone marrow (IBM) injection of whole
      bone marrow cells (BMCs) from allogeneic normal C57BL/6 (B6) mice (5.5 Gy x 2 +
      IBM). In MRL/lpr mice treated with this method, the number of donor-derived cells
      in the bone marrow, spleen, and liver rapidly increased (almost 100% donor
      derived cells by 14 days after the treatment), and the number of donor-derived
      hemopoietic progenitor cells concomitantly increased. Furthermore, donor-derived
      stromal cells were clearly detected in the cultured bone pieces from MRL/lpr mice
      treated with 5.5 Gy x 2 + IBM. All the recipients thus treated survived more than
      1 year (> 60 weeks after birth) and remained free from autoimmune diseases.
      Autoantibodies decreased to almost normal levels, and abnormal T cells
      (Thy1.2(+)/B220(+)/CD4(-)/CD8(-)) disappeared. Hematolymphoid cells were
      reconstituted with donor-derived cells, and newly developed T cells were tolerant
      to both donor (B6)-type and host (MRL/lpr)-type major histocompatibility complex
      determinants. Successful cooperation was achieved among T cells, B cells, and
      antigen-presenting cells when evaluated by in vitro antisheep red blood cell
      responses. These findings clearly indicate that this new strategy (IBM-BMT)
      creates the appropriate hemopoietic environment for the early recovery of
      hemopoiesis and donor cell engraftment, resulting in the complete amelioration of
      intractable autoimmune diseases in chimeric resistant MRL/lpr mice without
      recourse to immunosuppressants. This strategy would therefore be suitable for
      human therapy.

PMID- 11342462
TI  - Induction of monocyte tissue factor expression by antibodies to heparin-platelet
      factor 4 complexes developed in heparin-induced thrombocytopenia.
AB  - The pathogenesis of thrombosis in heparin-induced thrombocytopenia (HIT) was
      studied by investigating whether antibodies to heparin-platelet factor 4 (H-PF4)
      induced tissue factor (TF) synthesis by monocytes. Plasma from 5 patients with
      HIT containing IgG to H-PF4 was incubated with peripheral blood mononuclear cells
      without or with purified PF4 and heparin. Significant TF-dependent procoagulant
      activity (PCA) expressed by monocytes, measured with a factor Xa-based
      chromogenic assay, was induced after incubation of each HIT plasma sample. This
      monocyte PCA required the presence of PF4 and was inhibited by high
      concentrations of heparin. Furthermore, purified HIT IgG added to whole blood
      with PF4 and heparin also provoked significant synthesis of TF mRNA by monocytes,
      demonstrated by RT-PCR, and this effect was not observed with normal IgG. These
      findings strongly support the hypothesis that antibodies to PF4 developed in HIT
      trigger the production of tissue factor by monocytes, and this effect could
      account in vivo for hypercoagulability and thrombotic complications in affected
      patients.

PMID- 11342460
TI  - Rapid and efficient homing of human CD34(+)CD38(-/low)CXCR4(+) stem and
      progenitor cells to the bone marrow and spleen of NOD/SCID and NOD/SCID/B2m(null)
      mice.
AB  - Stem cell homing into the bone microenvironment is the first step in the
      initiation of marrow-derived blood cells. It is reported that human severe
      combined immunodeficient (SCID) repopulating cells home and accumulate rapidly,
      within a few hours, in the bone marrow and spleen of immunodeficient mice
      previously conditioned with total body irradiation. Primitive CD34(+)CD38(
      /low)CXCR4(+) cells capable of engrafting primary and secondary recipient mice
      selectively homed to the bone marrow and spleen, whereas CD34(-)CD38(-/low)Lin(-)
      cells were not detected. Moreover, whereas freshly isolated CD34(+)CD38(+/high)
      cells did not home, in vivo stimulation with granulocyte colony-stimulating
      factor as part of the mobilization process, or in vitro stem cell factor
      stimulation for 2 to 4 days, potentiated the homing capabilities of cytokine
      stimulated CD34(+)CD38(+) cells. Homing of enriched human CD34(+) cells was
      inhibited by pretreatment with anti-CXCR4 antibodies. Moreover, primitive
      CD34(+)CD38(-/low)CXCR4(+) cells also homed in response to a gradient of human
      stromal cell-derived factor 1 (SDF-1), directly injected into the bone marrow or
      spleen of nonirradiated NOD/SCID mice. Homing was also inhibited by pretreatment
      of CD34(+) cells with antibodies for the major integrins VLA-4, VLA-5, and LFA-1.
      Pertussis toxin, an inhibitor of signals mediated by Galpha(i) proteins,
      inhibited SDF-1-mediated in vitro transwell migration but not adhesion or in vivo
      homing of CD34(+) cells. Homing of human CD34(+) cells was also blocked by
      chelerythrine chloride, a broad-range protein kinase C inhibitor. This study
      reveals rapid and efficient homing to the murine bone marrow by primitive human
      CD34(+)CD38(-/low)CXCR4(+) cells that is integrin mediated and depends on
      activation of the protein kinase C signal transduction pathway by SDF-1.

PMID- 11342463
TI  - The basophil activation marker defined by antibody 97A6 is identical to the
      ectonucleotide pyrophosphatase/phosphodiesterase 3.
AB  - It has recently been shown that monoclonal antibody (MoAb) 97A6 detects a surface
      antigen expressed on basophils and their CD34(+) precursor cells, as well as the
      basophil cell line KU-812. In this report the partial amino acid sequence of
      affinity chromatography- and sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis-separated 97A6 antigen(s) from KU-812 lysates was determined.
      Sequence alignment of high-performance liquid chromatography-selected tryptic
      peptides from the resulting 130- and 150-kd bands revealed a 100% identity with
      amino acids 393 to 405 of ectonucleotide pyrophosphatase/phosphodiesterase-3 (E
      NPP3; CD203c) but not of the related ectoenzyme PC-1 (E-NPP1). Moreover, MoAb
      97A6 selectively recognized 293 cells transfected with human E-NPP3, but did not
      react with cells transfected with PC-1 or parental 293 cells. In addition, E-NPP3
      messenger RNA expression was detected in basophils but not other peripheral blood
      cells. Finally, MoAb 97A6 immunoprecipitated phosphodiesterase activity from KU
      812 cells and peripheral blood basophils, but not from other cell populations.
      These data demonstrate that MoAb 97A6 recognizes the functionally active type II
      transmembrane ectoenzyme E-NPP3.

PMID- 11342464
TI  - Human polymorphism of P-selectin glycoprotein ligand 1 attributable to variable
      numbers of tandem decameric repeats in the mucinlike region.
AB  - Platelet GP Ibalpha and leukocyte P-selectin glycoprotein ligand 1 (PSGL-1) are
      membrane mucins with a number of structural and functional similarities. It was
      investigated whether, like GP Ibalpha, PSGL-1 is affected by a variable number of
      tandem repeat polymorphism in its mucin-like region. By polymerase chain reaction
      amplification of the genomic region encoding the PSGL-1 repeats, 3 allelic
      variants were identified in the human population. The 3 alleles-A, B, and C-from
      largest to smallest, contained 16, 15, and 14 decameric repeats, respectively,
      with the B variant lacking repeat 2 and the C variant retaining repeat 2 but
      lacking repeats 9 and 10. Allele frequencies were highest for the A variant and
      lowest for the C variant in the 2 populations studied (frequencies of 0.81, 0.17,
      and 0.02 in white persons and 0.65, 0.35, and 0.00 in Japanese). Thus, PSGL-1 is
      highly polymorphic and contains a structural polymorphism that potentially
      indicates functional variation in the human population.

PMID- 11342465
TI  - Molecular genetic basis of porcine histo-blood group AO system.
AB  - Histo-blood group A and B antigens are oligosaccharide antigens important in
      transfusion and transplantation medicine. The final steps in the synthesis of
      these antigens are catalyzed by glycosyltransferases encoded by the functional
      alleles at the ABO locus. Humans have 3 major alleles (A, B, and O), whereas pigs
      are known to have only A and O alleles. This paper reports the molecular genetic
      basis of the porcine AO system. The porcine A gene is homologous to the ABO genes
      in humans and other species. It encodes an alpha1 --> 3 N-acetyl-D
      galactosaminyltransferase that synthesizes A antigens. Southern hybridization
      experiments using a porcine A gene coding-sequence probe failed to identify a
      corresponding homologous sequence in genomic DNA from group O pigs, thus
      suggesting a major deletion in the O gene. Therefore, inadvertent activation of a
      silent O gene seems unlikely in porcine organs xenotransplanted into humans.

PMID- 11342466
TI  - Induction of tolerance to human factor VIII in mice.
AB  - This paper reports loss of human factor VIII (hFVIII) inhibitory antibody in
      immunocompetent C57BL/6 mice. High-titer anti-hFVIII antibody developed in the
      mice within 7 to 14 days of intraportal administration of adeno-associated virus
      (AAV) carrying FVIII that coincided with a reduction in plasma hFVIII antigen.
      Bethesda titers (> 100 units) persisted relatively unchanged for 9 to 10 months.
      Unexpectedly, at 10 months after injection of the virus, hFVIII protein (up to 59
      ng/mL) was detected in 3 mice at the same time as disappearance of hFVIII
      inhibitor. The level of hFVIII was similar to that found in immunodeficient mice
      receiving the same dose of recombinant AAV carrying hFVIII without hFVIII
      inhibitor. These results suggest that tolerance to hFVIII can be induced by
      sustained expression of hFVIII in a mouse model. Further elucidation of this
      observation may affect use of FVIII gene transfer in the treatment of inhibitor
      positive patients with hemophilia A.

PMID- 11342467
TI  - On genetics, inflammation, and abdominal aortic aneurysm: can single nucleotide
      polymorphisms predict the outcome?

PMID- 11342469
TI  - Assessment of myocardial perfusion in coronary artery disease by magnetic
      resonance: a comparison with positron emission tomography and coronary
      angiography.
AB  - BACKGROUND: Monitoring contrast medium wash-in kinetics in hyperemic myocardium
      by magnetic resonance (MR) allows for the detection of stenosed coronary
      arteries. In this prospective study, the quality of a multislice MR approach with
      respect to the detection and sizing of compromised myocardium was determined and
      compared with positron emission tomography (PET) and quantitative coronary
      angiography. METHODS AND RESULTS: A total of 48 patients and healthy subjects
      were studied by MR using a multislice hybrid echo-planar pulse sequence for
      monitoring the myocardial first pass kinetics of gadolinium-diethylenetriamine
      pentaacetic acid bismethylamide (Omniscan; 0.1 mmol/kg injected at 3 mL/s IV)
      during hyperemia (dipyridamole 0.56 mg/kg). Signal intensity upslope as a measure
      of myocardial perfusion was calculated in 32 sectors per heart from pixelwise
      parametric maps in the subendocardial layer and for full wall thickness. Before
      coronary angiography, coronary flow reserve (hyperemia induced by dipyridamole
      0.56 mg/kg) was determined in corresponding sectors by (13)N-ammonia PET.
      Receiver-operator characteristic analysis of subendocardial upslope data revealed
      a sensitivity and specificity of 91% and 94%, respectively, for the detection of
      coronary artery disease as defined by PET (mean coronary flow reserve minus 2SD
      of controls) and a sensitivity and specificity of 87% and 85%, respectively, in
      comparison with quantitative coronary angiography (diameter stenosis >/=50%). The
      number of pathological sectors per patient on PET and MR studies correlated
      linearly (slope, 0.94; r=0.76; P<0.0001). CONCLUSIONS: The presented MR approach
      reliably identifies patients with coronary artery stenoses and provides
      information on the amount of compromised myocardium, even when perfusion
      abnormalities are confined to the subendocardial layer. This modality may qualify
      for its clinical application in the management of coronary artery disease.

PMID- 11342468
TI  - Premature atherosclerosis associated with monogenic insulin resistance.
AB  - BACKGROUND: The common insulin resistance syndrome, with obesity, dyslipidemia,
      hyperglycemia, and hypertension, is associated with increased risk of
      atherosclerosis. Early atherosclerosis in rare monogenic forms of insulin
      resistance, however, has not been extensively documented. Cardiovascular end
      points were thus evaluated in subjects with Dunnigan-type familial partial
      lipodystrophy (FPLD) due to mutations at LMNA codon 482. METHODS AND RESULTS:
      FPLD subjects >/=35 years old were stratified by genotype for either the LMNA
      R482Q or R482W mutation. Twenty-three subjects were heterozygous mutation
      carriers, and 17 were R482/R482 homozygous family control subjects. All LMNA
      mutation carriers had FPLD with insulin resistance. In addition, LMNA mutation
      carriers had significantly more type 2 diabetes, hypertension, and dyslipidemia
      than normal family control subjects. Eight LMNA mutation carriers had coronary
      heart disease (CHD), compared with 1 normal control subject (OR 5.9, 95% CI 1.2
      to 30.2). Six LMNA mutation carriers had CHD end points before age 55 years, and
      4 of these, all women, had been hospitalized for CABG surgery between the ages of
      35 and 54 years. CONCLUSIONS: Rare LMNA mutations that underlie FPLD with insulin
      resistance and hyperinsulinemia are also associated with early CHD, notably in
      women. This suggests that abnormalities of the nuclear envelope can result in a
      phenotype that recapitulates most of the important attributes of the common
      insulin resistance syndrome, including accelerated cardiovascular disease. FPLD
      thus appears to be an appropriate human monogenic model for the common insulin
      resistance syndrome.

PMID- 11342470
TI  - Enhanced response of blood monocytes to in vitro lipopolysaccharide-challenge in
      patients with recurrent unstable angina.
AB  - BACKGROUND: C-reactive protein (CRP) plasma levels have been associated with
      short- and long-term occurrence of coronary events. We investigated whether
      circulating inflammatory cell responsiveness to low-grade stimuli could
      contribute to the reported association between CRP and coronary events. METHODS
      AND RESULTS: We studied 32 patients with unstable angina who were followed for 24
      months and were free of symptoms for 6 months (group 1): 19 patients had
      persistently high CRP levels (>0.3 mg/dL) (group 1A); 13 patients had normal CRP
      levels (group 1B). During the follow-up, 12 (63%) group 1A but no group 1B
      patients developed an infarction or recurrence of unstable angina (P<0.001).
      Eighteen patients with chronic stable angina (group 2) and 18 healthy subjects
      (group 3) were studied as controls. Interleukin (IL)-6 production (median, range)
      by peripheral blood mononuclear cells after 4 hours of in vitro stimulation with
      1 ng/mL lipopolysaccharide (LPS) was significantly higher in group 1A (4526
      pg/mL, 3042 to 10 583 pg/mL) than in group 1B (1752 pg/mL, 75 to 3981 pg/mL),
      group 2 (707 pg/mL, 41 to 3275 pg/mL), and group 3 (488 pg/mL, 92 to 3503 pg/mL)
      (all P<0.001). No significant differences were observed among the other groups.
      IL-6 production after LPS-challenge was correlated with baseline CRP levels
      (r=0.42, P=0.005). CONCLUSIONS: Mononuclear cells of patients with recurrent
      phases of instability exhibit an enhanced production of IL-6 in response to low
      dose of LPS, correlated with baseline CRP levels, 6 months after the last acute
      event. This persisting enhanced acute-phase responsiveness may help explain the
      association between CRP and acute coronary events.

PMID- 11342471
TI  - Chromosomal location, exon structure, and vascular expression patterns of the
      human PDGFC and PDGFD genes.
AB  - BACKGROUND: Platelet-derived growth factor (PDGF), which is a major mitogen for
      vascular smooth muscle cells and has been implicated in the pathogenesis of
      arteriosclerosis, is composed of dimers of PDGF-A and PDGF-B polypeptide chains,
      encoded by different genes. Here, we have analyzed the chromosomal localization,
      structure, and expression of 2 newly identified human genes of the PDGF family,
      called PDGFC and PDGFD. METHODS AND RESULTS: We used fluorescence in situ
      hybridization to locate PDGFC and PDGFD in chromosomes 4q32 and 11q22.3 to 23.2,
      respectively. Exon structures of PDGFC and PDGFD were determined by sequencing
      from genomic DNA clones. The coding region of PDGFC consists of 6 and PDGFD of 7
      exons, of which the last 2 encode the C-terminal PDGF cystine knot growth factor
      homology domain. An N-terminal CUB domain is encoded by exons 2 and 3 of both
      genes, and a region of proteolytic cleavage involved in releasing and activating
      the growth factor domain is located in exon 4 in PDGFC and exon 5 in PDGFD. PDGF
      C was expressed predominantly in smooth muscle cells and PDGF-D in fibroblastic
      adventitial cells, and both genes were active in cultured endothelial cells and
      in a variety of tumor cell lines. Both PDGF-C and PDGF-D also stimulated human
      coronary artery smooth muscle cells. CONCLUSIONS: PDGFC and PDGFD have similar
      genomic structures, which resemble those of the PDGFA and PDGFB genes. Their
      expression in the arterial wall and cultured vascular cells suggests that they
      can transduce proliferation/migration signals to pericytes and smooth muscle
      cells.

PMID- 11342472
TI  - Simvastatin depresses blood clotting by inhibiting activation of prothrombin,
      factor V, and factor XIII and by enhancing factor Va inactivation.
AB  - BACKGROUND: The mechanism of the antithrombotic action of statins is unclear. The
      aim of this study was to evaluate the effects of simvastatin on the coagulation
      process at sites of microvascular injury. METHODS AND RESULTS: Tissue factor
      initiated coagulation was assessed in blood samples collected every 30 seconds
      from bleeding-time wounds of 17 patients who had advanced coronary artery disease
      and total cholesterol levels of 224.6+/-11.8 mg/dL (mean+/-SEM). Quantitative
      Western blotting for time courses of fibrinogen depletion and activation of
      prothrombin, factor V, and factor XIII was performed before and after 3 months of
      simvastatin treatment (20 mg/d). Simvastatin induced reductions in total
      cholesterol (23%) and LDL-cholesterol (36%), which were accompanied by
      significant decreases in the rates of prothrombin activation (16.2+/-2.1%;
      P=0.004), formation of alpha-thrombin B-chain (27.4+/-1.8%; P=0.001), generation
      of factor Va heavy chain (29.7+/-3.1%; P=0.007) and factor Va light chain (18.9+/
      1.2%; P=0.02), factor XIII activation (19.8+/-1.3%; P=0.001), and fibrinogen
      conversion to fibrin (72.2+/-3%; P=0.002). Posttreatment fibrinopeptides A and B
      concentrations, determined by using high-performance liquid chromatography, were
      reduced within the last 30 seconds of bleeding. The 30-kDa fragment of the factor
      Va heavy chain (residues 307 to 506), produced by activated protein C, and the 97
      kDa fragment of the factor Va heavy chain (residues 1 to 643) were released more
      rapidly after simvastatin treatment. The antithrombotic actions of simvastatin
      showed no relationship to its cholesterol-lowering action. CONCLUSIONS:
      Simvastatin treatment depresses blood clotting, which leads to reduced rates of
      prothrombin activation, factor Va generation, fibrinogen cleavage, factor XIII
      activation, and an increased rate of factor Va inactivation. These effects are
      not related to cholesterol reduction.

PMID- 11342473
TI  - Controlled trial of intravenous immune globulin in recent-onset dilated
      cardiomyopathy.
AB  - BACKGROUND: This prospective placebo-controlled trial was designed to determine
      whether intravenous immune globulin (IVIG) improves left ventricular ejection
      fraction (LVEF) in adults with recent onset of idiopathic dilated cardiomyopathy
      or myocarditis. METHODS AND RESULTS: Sixty-two patients (37 men, 25 women; mean
      age +/-SD 43.0+/-12.3 years) with recent onset (</=6 months of symptoms) of
      dilated cardiomyopathy and LVEF </=0.40 were randomized to 2 g/kg IVIG or
      placebo. All underwent an endomyocardial biopsy before randomization, which
      revealed cellular inflammation in 16%. The primary outcome was change in LVEF at
      6 and 12 months after randomiz. Overall, LVEF improved from 0.25+/-0.08 to 0.41+/
      0.17 at 6 months (P<0.001) and 0.42+/-0.14 (P<0.001 versus baseline) at 12
      months. The increase was virtually identical in patients receiving IVIG and those
      given placebo (6 months: IVIG 0.14+/-0.12, placebo 0.14+/-0.14; 12 months: IVIG
      0.16+/-0.12, placebo 0.15+/-0.16). Overall, 31 (56%) of 55 patients at 1 year had
      an increase in LVEF >/=0.10 from study entry, and 20 (36%) of 56 normalized their
      ejection fraction (>/=0.50). The transplant-free survival rate was 92% at 1 year
      and 88% at 2 years. CONCLUSIONS: These results suggest that for patients with
      recent-onset dilated cardiomyopathy, IVIG does not augment the improvement in
      LVEF. However, in this overall cohort, LVEF improved significantly during follow
      up, and the short-term prognosis remains favorable.

PMID- 11342474
TI  - Interleukin-6 (IL-6) and the prognosis of abdominal aortic aneurysms.
AB  - BACKGROUND: Abdominal aortic aneurysm is a multifactorial disorder in which
      inflammation is an important pathophysiological feature. In explant culture,
      aneurysm biopsies secrete large amounts of interleukin-6 (IL-6), and among
      aneurysm patients, the circulating concentration of IL-6 appears to be increased.
      METHODS AND RESULTS: We investigated, in 19 patients, whether aneurysm wall was
      an important source of circulating IL-6. We also tested the hypotheses, in 466
      patients with a small aneurysm, that (1) high concentrations of circulating IL-6
      signaled rapid aneurysm growth and (2) the -174 G-->C polymorphism in the IL-6
      promoter predicted survival. For 19 patients with large or inflammatory
      aneurysms, the concentration of IL-6 was higher in the iliac arteries than the
      brachial arteries (median difference 26.5 pg/mL, this difference increasing with
      aneurysm diameter, P=0.01). In 466 patients with small aneurysms, the frequency
      of the -174 C allele (0.40) was similar to that in a normal healthy population.
      Patients of GG genotype had lower plasma concentrations of IL-6 than patients of
      GC and CC genotypes (medians 1.9, 4.8, and 15.6 pg/mL, respectively, Kruskal
      Wallis P=0.047). Cardiovascular and all-cause mortalities were lower for patients
      of GG genotype than for patients of GC and CC genotype: hazard ratios 0.32 (95%
      CI 0.12 to 0.93), P=0.036, and 0.51 (95% CI 0.25 to 1.00), P=0.05, respectively.
      There was no association between plasma IL-6 or IL-6 genotype and aneurysm
      growth. CONCLUSIONS: Aortic aneurysms appear to be an important source of
      circulating IL-6, the concentration being influenced by genotype. For patients
      with small aneurysms, the -174 G-->C IL-6 genotype predicts future cardiovascular
      mortality.

PMID- 11342475
TI  - Atrial reentrant tachycardia after surgery for congenital heart disease:
      endocardial mapping and radiofrequency catheter ablation using a novel,
      noncontact mapping system.
AB  - BACKGROUND: The purpose of the present study was to determine the role of a
      novel, noncontact mapping system for assessing a variety of atrial reentrant
      tachycardias (ART) in patients after the surgical correction of congenital heart
      disease. METHODS AND RESULTS: In 14 patients, an electrophysiological study using
      the Ensite 3000 system was performed to assess ARTs resistant to medical
      treatment. Sixteen different forms of ART were inducible in the 14 patients
      studied. The reentrant circuit of all ARTs could be characterized and localized
      with respect to anatomic landmarks such as atriotomy scars, intraatrial
      patches/baffles, and cardiac structures. In 15 of the 16 ARTs (in 13 of the 14
      patients), a target area of the reentrant circuit for radiofrequency current
      application (ie, an area of conduction between 2 anatomical obstacles such as
      surgical barriers and cardiac structures of electrical isolation) could be
      localized within the systemic venous atrium. Nine patients exhibited
      macroreentry, and 4 showed microreentry. In 12 patients, ART could be terminated
      by creating linear radiofrequency current lesions (75 degrees C, 180 to 390 s).
      Completeness of linear lesions after radiofrequency current delivery was proven
      by analyzing color-coded isopotential maps of atrial activation while applying
      atrial pacing techniques. The mean duration of the procedures was 286 minutes
      (range, 130 to 435 minutes); fluoroscopy time ranged from 7 to 33.8 minutes
      (mean, 17.4 minutes). CONCLUSIONS: In patients with ART after the surgical
      correction of congenital heart disease, the use of the noncontact mapping system
      allows for characterization of the tachycardia and guidance for effective
      radiofrequency current delivery.

PMID- 11342476
TI  - Influence of hypoxia on nitric oxide synthase activity and gene expression in
      children with congenital heart disease: a novel pathophysiological adaptive
      mechanism.
AB  - BACKGROUND: Chronic hypoxia has been shown to modulate nitric oxide (NO)
      responses in different cell models, but the relationship between hypoxia and NO
      synthase (NOS) regulation in humans was not studied. We studied the relationship
      between endothelial and inducible NOS (eNOS and iNOS) activities and expression
      and chronic hypoxia in children with cyanotic and acyanotic congenital heart
      defects. METHODS AND RESULTS: Right atrial tissue was excised from 18 patients
      during cardiac surgery. eNOS and iNOS activities were measured by conversion of L
      [H(3)]arginine to L-[H(3)]citrulline. Gene expression of eNOS and iNOS was
      quantified by competitive reverse transcription-polymerase chain reaction. The
      eNOS activity and expression were significantly reduced in cyanotic hearts
      compared with acyanotic hearts: 0.38+/-0.14 versus 1.06+/-0.11 pmol. mg(-1). min(
      1) (P<0.0001) and 0.54+/-0.08 versus 0.80+/-0.10 relative optical density (ROD)
      of cDNA (P<0.0001), respectively. In contrast, iNOS activity and expression were
      significantly higher in cyanotic than in acyanotic children: 7.04+/-1.20 versus
      4.17+/-1.10 pmol. mg(-1). min(-1) (P<0.0001) and 2.55+/-0.11 versus 1.91+/-0.18
      ROD of cDNA (P<0.0001), respectively. CONCLUSIONS: Hypoxia downregulates eNOS
      activity and gene expression in cardiac tissue from patients with cyanotic
      congenital heart defects. By contrast, iNOS activity and expression are increased
      in cyanotic children and may represent an alternative mechanism to counteract the
      effects of hypoxia in the cardiovascular system. Therefore, a novel adaptive
      mechanism during hypoxia is suggested.

PMID- 11342477
TI  - Absence of 12/15-lipoxygenase expression decreases lipid peroxidation and
      atherogenesis in apolipoprotein e-deficient mice.
AB  - BACKGROUND: The enzyme 12/15-lipoxygenase (12/15-LO) has been implicated in the
      oxidative modification of LDL. In a murine model, we tested the hypothesis that
      deletion of 12/15-LO decreases atherogenesis by reducing oxidant stress, as
      measured by 2 indices of lipid peroxidation: isoprostane generation and
      autoantibody formation to malondialdehyde (MDA)-LDL, an epitope of LDL formed as
      a result of oxidative modification. METHODS AND RESULTS: 12/15-LO-deficient
      (12/15-LO(-/-)) mice were crossed with apolipoprotein E-deficient (apoE(-/-))
      mice. At 10 weeks of age, atherosclerotic lesion initiation was significantly
      delayed in the double-knockout mice. The rate of lesion progression was
      diminished at 8 and 12 months, and even at 15 months, lesion size was reduced 50%
      (P<0.0005) compared with control apoE(-/-) mice. The urinary and plasma levels of
      the specific isoprostane 8,12-iso-iPF(2alpha)-VI, as well as IgG autoantibodies
      against MDA-LDL, were significantly reduced in the double-deficient mice in
      parallel with decreased atherosclerosis at all time points from 10 weeks to 15
      months of age compared with apoE(-/-) controls. CONCLUSIONS: Enzymatic action of
      12/15-LO contributes significantly to atherosclerotic lesion initiation and
      propagation in this murine model. Strong positive correlations exist between
      lesion size, isoprostane levels, and MDA-LDL autoantibodies, providing in vivo
      evidence for an enzymatic (12/15-LO) component to lipid peroxidation and
      atherogenesis.

PMID- 11342478
TI  - High-density lipoprotein loses its anti-inflammatory properties during acute
      influenza a infection.
AB  - BACKGROUND: Viruses have been identified as one of a variety of potential agents
      that are implicated in atherogenesis. METHODS AND RESULTS: C57BL/6J mice were
      killed before or 2, 3, 5, 7, or 9 days after intranasal infection with 10(5)
      plaque-forming units (pfu) of Influenza A strain WSN/33. Peak infectivity in
      lungs was reached by 72 hours, and it returned to baseline by 9 days. No viremia
      was observed at any time. The activities of paraoxonase and platelet-activating
      factor acetylhydrolase in HDL decreased after infection and reached their lowest
      levels 7 days after inoculation. The ability of HDL from infected mice to inhibit
      LDL oxidation and LDL-induced monocyte chemotactic activity in human artery wall
      cell cocultures decreased with time after inoculation. Moreover, as the infection
      progressed, LDL more readily induced monocyte chemotaxis. Peak interleukin-6 and
      serum amyloid A plasma levels were observed at 2 and 7 days after inoculation.
      HDL apoA-I levels did not change. ApoJ and ceruloplasmin levels in HDL peaked 3
      days after infection. Ceruloplasmin remained elevated throughout the time course,
      whereas apoJ levels decreased toward baseline after the third day. CONCLUSIONS:
      We conclude that alterations in the relative levels of paraoxonase, platelet
      activating factor acetylhydrolase, ceruloplasmin, and apoJ in HDL occur during
      acute influenza infection, causing HDL to lose its anti-inflammatory properties.

PMID- 11342479
TI  - Paclitaxel stent coating inhibits neointimal hyperplasia at 4 weeks in a porcine
      model of coronary restenosis.
AB  - BACKGROUND: Despite limiting elastic recoil and late vascular remodeling after
      angioplasty, coronary stents remain vulnerable to restenosis, caused primarily by
      neointimal hyperplasia. Paclitaxel, a microtubule-stabilizing drug, has been
      shown to inhibit vascular smooth muscle cell migration and proliferation
      contributing to neointimal hyperplasia. We tested whether paclitaxel-coated
      coronary stents are effective at preventing neointimal proliferation in a porcine
      model of restenosis. METHODS AND RESULTS: Palmaz-Schatz stents were dip-coated
      with paclitaxel (0, 0.2, 15, or 187 microgram/stent) by immersion in ethanolic
      paclitaxel and evaporation of the solvent. Stents were deployed with mild
      oversizing in the left anterior descending coronary artery (LAD) of 41 minipigs.
      The treatment effect was assessed 4 weeks after stent implantation. The
      angiographic late loss index (mean luminal diameter) decreased with increasing
      paclitaxel dose (P<0.0028 by ANOVA), declining by 84.3% (from 0.352 to 0.055,
      P<0.05) at the highest level tested (187 microgram/stent versus control).
      Accompanying this change, the neointimal area decreased (by 39.5%, high-dose
      versus control; P<0.05) with increasing dose (P<0.040 by ANOVA), whereas the
      luminal area increased (by 90.4%, high-dose versus control; P<0.05) with
      escalating dose (P<0.0004 by ANOVA). Inflammatory cells were seen infrequently,
      and there were no cases of aneurysm or thrombosis. CONCLUSIONS: Paclitaxel-coated
      coronary stents produced a significant dose-dependent inhibition of neointimal
      hyperplasia and luminal encroachment in the pig LAD 28 days after implantation;
      later effects require further study. These results demonstrate the potential
      therapeutic benefit of paclitaxel-coated coronary stents in the prevention and
      treatment of human coronary restenosis.

PMID- 11342480
TI  - Ischemia-reperfusion of rat myocardium activates nuclear factor-KappaB and
      induces neutrophil infiltration via lipopolysaccharide-induced CXC chemokine.
AB  - BACKGROUND: Mechanisms by which neutrophils are attracted to the myocardium in
      ischemia/reperfusion are not fully defined. Lipopolysaccharide-induced CXC
      chemokine (LIX), cytokine-induced neutrophil chemoattractant (KC), and macrophage
      inflammatory protein-2 (MIP-2) are rodent chemokines with potent neutrophil
      chemotactic activity. The goals of the present study were to evaluate the roles
      of these chemokines in a rat model of ischemia/reperfusion and to examine the
      mechanisms of chemokine induction by oxidative stress and cytokines in cultured
      cardiomyocytes. METHODS AND RESULTS: Male Wistar-Kyoto rats underwent 45 minutes
      of ligation of the left anterior descending coronary artery, followed by
      reperfusion for various periods. Compared with sham-operated controls, myocardium
      from reperfused animals had higher levels of free radicals, increased neutrophil
      infiltration evidenced histologically and by elevated myeloperoxidase activity,
      and increased nuclear factor (NF)-kappaB DNA binding activity. Ischemia
      reperfusion also induced the expression of interleukin-1beta, tumor necrosis
      factor (TNF)-alpha, LIX, KC, and MIP-2 mRNA and protein. LIX expression was
      localized to resident myocardial cells, whereas KC and MIP-2 were expressed only
      in infiltrating inflammatory cells. Neutralization of LIX inhibited 79% of
      neutrophil infiltration into previously ischemic myocardium. In contrast,
      neutralization of KC and MIP-2 reduced neutrophil infiltration by only 28% and
      37%, respectively. In cultured cardiomyocytes, LIX expression was induced by
      oxidative stress or TNF-alpha and was blocked by the NF-kappaB inhibitor
      pyrrolidinedithiocarbamate. CONCLUSIONS: LIX is expressed by resident myocardial
      cells during ischemia-reperfusion and is induced in cultured cardiomyocytes by
      oxidative stress or TNF-alpha via NF-kappaB activation. Although KC and MIP-2 are
      expressed by inflammatory cells infiltrating the myocardium during reperfusion
      after ischemia, neutrophil recruitment to reperfused rat myocardium is mainly due
      to cardiomyocyte expression of LIX.

PMID- 11342482
TI  - The search for replacements for unfractionated heparin.

PMID- 11342481
TI  - Matrix metalloproteinase inhibition attenuates left ventricular remodeling and
      dysfunction in a rat model of progressive heart failure.
AB  - BACKGROUND: Matrix metalloproteinase (MMP) activation contributes to tissue
      remodeling in several disease states, and increased MMP activity has been
      observed in left ventricular (LV) failure. The present study tested the
      hypothesis that MMP inhibition would influence LV remodeling and function in
      developing LV failure. METHODS AND RESULTS: LV size and function were measured in
      5 groups of rats: (1) obese male spontaneously hypertensive heart failure rats
      (SHHF) at 9 months (n=10), (2) SHHF at 13 months (n=12), (3) SHHF rats treated
      with an MMP inhibitor during months 9 to 13 (PD166793 5 mg. kg(-1). d(-1) PO;
      n=14), (4) normotensive Wistar-Furth rats (WF) at 9 months (n=12), and (5) WF at
      13 months (n=12). Plasma concentrations of the MMP inhibitor (116+/-11
      micromol/L) reduced in vitro LV myocardial MMP-2 activity by approximately 100%.
      LV function and geometry were similar in WF rats at 9 and 13 months. LV peak
      +dP/dt was unchanged at 9 months in SHHF but by 13 months was reduced in the SHHF
      group compared with WF (3578+/-477 versus 5983+/-109 mm Hg/s, P</=0.05). LV
      volume measured at an equivalent ex vivo pressure (10 mm Hg) was increased in
      SHHF at 9 months compared with WF (443+/-12 versus 563+/-33 mL, P</=0.05) and
      increased further by 13 months (899+/-64 mL, P</=0.05). LV myocardial MMP-2
      activity was increased by approximately 2-fold in SHHF at 9 and 13 months. With
      MMP inhibition, LV peak +dP/dt was similar to WF values and LV volume was reduced
      compared with untreated SHHF values (678+/-28 mL, P</=0.05). CONCLUSIONS: MMP
      activity contributes to LV dilation and progression to LV dysfunction in a rodent
      HF model, and direct MMP inhibition can attenuate this process.

PMID- 11342483
TI  - Resolution of stress-induced myocardial ischemia during aggressive medical
      therapy as demonstrated by single photon emission computed tomography imaging.

PMID- 11342484
TI  - Acute endothelin a receptor blockade in heart failure.

PMID- 11342486
TI  - Myocardial infarction after dog bite.

PMID- 11342485
TI  - Myocardial infarction after dog bite.

PMID- 11342487
TI  - Myocardial infarction after dog bite.

PMID- 11342488
TI  - Impairment of ventilatory efficiency in heart failure.

PMID- 11342492
TI  - Are cribs the safest place for infants to sleep? Yes: bed sharing is too
      hazardous.

PMID- 11342493
TI  - Are cribs the safest place for infants to sleep? No: evidence supports respecting
      informed parental preference.

PMID- 11342494
TI  - The cost to global health of drug company profits.

PMID- 11342496
TI  - The helix and health: applying genetics to primary care.

PMID- 11342498
TI  - Bush's initiative could help groups that promote faith healing.

PMID- 11342497
TI  - Protein can predict survival from breast cancer.

PMID- 11342499
TI  - A belt buckle allergy?

PMID- 11342501
TI  - The prevention and cure of physician burnout.

PMID- 11342503
TI  - Effects of patients' preferences on the treatment of atrial fibrillation:
      observational study of patient-based decision analysis.
AB  - OBJECTIVE: To investigate the effect of patients' preferences in the treatment of
      atrial fibrillation by using individualized decision analysis in which
      probability and utility assessments are combined into a decision tree. DESIGN:
      Observational study based on interviews with patients. SETTING: 8 general
      practices in Avon, England. PARTICIPANTS: 260 randomly selected patients aged 70
      to 85 years with atrial fibrillation. MAIN OUTCOME MEASURES: Patients' treatment
      preferences regarding anticoagulation treatment (warfarin sodium) after
      individualized decision analysis; comparison of these preferences with treatment
      guidelines on the basis of comorbidity and absolute risk and compared with
      current prescription. RESULTS: Of 195 eligible patients, 97 participated in
      decision making using decision analysis. Among these 97, the decision analysis
      indicated that 59 (61%; 95% confidence interval, 50%-71%) would prefer
      anticoagulation treatment, considerably fewer than those who would be recommended
      treatment according to guidelines. There was marked disagreement between the
      decision analysis and guideline recommendations (kappa> or =0.25). Of 38 patients
      whose decision analysis indicated a preference for anticoagulation, 17 (45%) were
      being prescribed warfarin; on the other hand, 28 (47%) of 59 patients were not
      being prescribed warfarin, although the results of their decision analysis
      suggested they wanted to be. CONCLUSIONS: In the context of shared decision
      making, individualized decision analysis is valuable in a sizable proportion of
      elderly patients with atrial fibrillation. Taking account of patients'
      preferences would lead to fewer prescriptions for warfarin than under published
      recommendations. Decision analysis as a shared decision-making tool should be
      evaluated in a randomized controlled trial.

PMID- 11342504
TI  - Toward a more practical decision analysis: a patient's perspective.

PMID- 11342505
TI  - Patients, preferences, and evidence.

PMID- 11342506
TI  - The relation of family violence, employment status, welfare benefits, and alcohol
      drinking in the United States.
AB  - OBJECTIVE: To examine the contribution of employment status, welfare benefits,
      alcohol use, and other individual and contextual factors to physical aggression
      during marital conflict. METHODS: Logistic regression models were used to analyze
      panel data collected in the National Survey of Families and Households in 1987
      and 1992. A total of 4,780 married or cohabiting persons reinterviewed in 1992
      were included in the analysis. Domestic violence was defined as reporting that
      both partners were physically violent during arguments. RESULTS: Unemployed
      respondents are not at greater risk of family violence than employed respondents,
      after alcohol misuse, income, education, age, and other factors are controlled
      for; however, employed persons receiving welfare benefits are at significantly
      higher risk. Alcohol misuse, which remains a predictor of violence even after
      other factors are controlled for, increases the risk of family violence, and
      satisfaction with social support from family and friends is associated with its
      decrease. CONCLUSIONS: Alcohol misuse has an important effect on domestic
      violence, and the potential impact of welfare reform on domestic violence needs
      to be monitored.

PMID- 11342507
TI  - Clinicians, intimate partner violence, and opportunities.

PMID- 11342510
TI  - Above all, do no harm: assessing the risk of an adverse reaction.

PMID- 11342512
TI  - Coronary artery disease: part 2. Treatment.

PMID- 11342518
TI  - Genetic testing.

PMID- 11342513
TI  - Psychological effect of genetic testing for Huntington's disease: an update of
      the literature.

PMID- 11342519
TI  - Oral cancer.

PMID- 11342521
TI  - What do I do now?

PMID- 11342522
TI  - Witnessing unethical conduct: the effects.

PMID- 11342524
TI  - How is Darwinian medicine useful?

PMID- 11342525
TI  - Evolution and our environment: will we adapt?

PMID- 11342526
TI  - No shrinking violet: Rose Kushner and the rise of American breast cancer
      activism.

PMID- 11342528
TI  - Oxygen sensing and HIF-1 activation does not require an active mitochondrial
      respiratory chain electron-transfer pathway.
AB  - Hypoxia induces the stabilization and transcriptional activation of the hypoxia
      inducible factor 1alpha (HIF-1alpha) protein, the regulatory member of the HIF-1
      complex. The molecular mechanisms that are responsible for oxygen sensing and the
      downstream pathways utilized by the hypoxic signal are still poorly understood.
      One hypothesis for oxygen sensing has postulated that reactive oxygen species
      generated at mitochondrial complex III are the initiators of the hypoxic signal.
      Here we find that mitochondrial DNA-less (rho(o)) cells have a normal response to
      hypoxia, measured at the level of HIF-1alpha protein stabilization, nuclear
      translocation, and its transcriptional activation activity. Furthermore,
      overexpression of catalase, either in the mitochondria or in the cytosol, fails
      to modify the hypoxia response indicating that hydrogen peroxide is not a
      signaling molecule in the hypoxic signaling cascade that culminates with HIF-1
      activation.

PMID- 11342529
TI  - Leptin induces mitochondrial superoxide production and monocyte chemoattractant
      protein-1 expression in aortic endothelial cells by increasing fatty acid
      oxidation via protein kinase A.
AB  - Leptin, a circulating hormone secreted mainly from adipose tissues, is involved
      in the control of body weight. The plasma concentrations are correlated with body
      mass index, and are reported to be high in patients with insulin resistance,
      which is one of the major risk factors for cardiovascular disease. However, the
      direct effect of leptin on vascular wall cells is not fully understood. In this
      study, we investigated the effects of leptin on reactive oxygen species (ROS)
      generation and expression of monocyte chemoattractant protein-1 (MCP-1) in bovine
      aortic endothelial cells (BAEC). We found that leptin increases ROS generation in
      BAEC in a dose-dependent manner and that its effects are additive with those of
      glucose. Rotenone, thenoyltrifluoroacetone (TTFA), carbonyl cyanide m
      chlorophenylhydrazone (CCCP), Mn(III)tetrakis (4-benzoic acid) porphyrin
      (MnTBAP), uncoupling protein-1 (UCP1) HVJ-liposomes, or manganese superoxide
      dismutase (MnSOD) HVJ-liposomes completely prevented the effect of leptin,
      suggesting that ROS arise from mitochondrial electron transport. Leptin increased
      fatty acid oxidation by stimulating the activity of carnitine
      palmitoyltransferase-1 (CPT-1) and inhibiting that of acetyl-CoA carboxylase
      (ACC), pace-setting enzymes for fatty acid oxidation and synthesis, respectively.
      Leptin-induced ROS generation, CPT-1 activation, ACC inhibition, and MCP-1
      overproduction were found to be completely prevented by either genistein, a
      tyrosine kinase inhibitor, H-89, a protein kinase A (PKA) inhibitor, or
      tetradecylglycidate, a CPT-1 inhibitor. Leptin activated PKA, and the effects of
      leptin were inhibited by the cAMP antagonist Rp-cAMPS. These results suggest that
      leptin induces ROS generation by increasing fatty acid oxidation via PKA
      activation, which may play an important role in the progression of
      atherosclerosis in insulin-resistant obese diabetic patients.

PMID- 11342530
TI  - Identification of a target site in plasminogen activator inhibitor-1 that allows
      neutralization of its inhibitor properties concomitant with an allosteric up
      regulation of its antiadhesive properties.
AB  - The serpin plasminogen activator inhibitor-1 (PAI-1) has a dual function: 1) it
      plays an important role as a direct inhibitor of the plasminogen activation
      system, and 2) its interaction with the adhesive glycoprotein vitronectin
      suggests a role in tissue remodeling and metastasis, independent from its
      proteinase inhibitory properties. Unique to this serpin is the close association
      between its conformational and functional properties. Indeed, PAI-1 can occur in
      an active and a latent conformation, but both functions are exclusively present
      in the active conformation. We report here the epitope localization and
      functional effects of a monoclonal antibody (MA-124K1) that inhibits rat PAI-1
      activity and simultaneously increases the binding of inactive PAI-1 to
      vitronectin (the affinity constant of PAI-1 for vitronectin is 2 x 10(7) m(-1) in
      the absence of MA-124K1 and 160 x 10(7) m(-1) in the presence of MA-124K1). To
      the best of our knowledge, this is the first monoclonal antibody dissociating the
      proteinase inhibitory properties from the vitronectin binding properties in PAI
      1. Mutation of Glu(212) and/or Glu(220) in rat PAI-1 to Ala results in a strongly
      reduced affinity or absence of binding to MA-124K1. The three-dimensional
      structure of PAI-1 reveals that these residues constitute a conformational
      epitope close to the reactive-site loop and compatible with the effect of MA
      124K1 on the inhibitory properties of PAI-1. However, the vitronectin binding
      site is localized at the opposite site of the molecule, indicating that the
      effect of MA-124K1 involves an allosteric modulation of the vitronectin binding
      site. Cell culture experiments revealed a significant reduction of cell
      attachment and migration in the presence of MA-124K1, providing evidence for the
      functional relevance of this antibody-mediated up-regulation of the vitronectin
      binding properties of PAI-1. In conclusion, a novel mechanism for interference
      with PAI-1 functions has been identified and is of importance in the modulation
      of cell migration and related events (e.g. tumor metastasis).

PMID- 11342531
TI  - Suppressors of cytokine signaling-1 and -6 associate with and inhibit the insulin
      receptor. A potential mechanism for cytokine-mediated insulin resistance.
AB  - Insulin resistance contributes to a number of metabolic disorders, including type
      II diabetes, hypertension, and atherosclerosis. Cytokines, such as tumor necrosis
      factor-alpha, interleukin-1 beta, and interleukin-6, and hormones, such as growth
      hormone, are known to cause insulin resistance, but the mechanisms by which they
      inhibit the cellular response to insulin have not been elucidated. One mechanism
      by which these agents could cause insulin resistance is by inducing the
      expression of cellular proteins that inhibit insulin receptor (IR) signaling.
      Suppressors of cytokine signaling (SOCS) proteins are negative regulators of
      cytokine signaling pathways, the expression of which is regulated by certain
      cytokines. SOCS proteins are therefore attractive candidates as mediators of
      cytokine-induced insulin resistance. We have found that SOCS-1 and SOCS-6
      interact with the IR when expressed in human hepatoma cells (HepG2) or in rat
      hepatoma cells overexpressing the human IR. In SOCS-1-expressing cells, insulin
      treatment increases the extent of interaction with the IR, whereas in SOCS-6
      expressing cells the association with the IR appears to require insulin
      treatment. SOCS-1 and SOCS-6 do not inhibit insulin-dependent IR
      autophosphorylation, but both proteins inhibit insulin-dependent activation of
      ERK1/2 and protein kinase B in vivo and IR-directed phosphorylation of IRS-1 in
      vitro. These results suggest that SOCS proteins may be inhibitors of IR signaling
      and could mediate cytokine-induced insulin resistance and contribute to the
      pathogenesis of type II diabetes.

PMID- 11342532
TI  - Potentiation of insulin-related signal transduction by a novel protein-tyrosine
      phosphatase inhibitor, Et-3,4-dephostatin, on cultured 3T3-L1 adipocytes.
AB  - We previously isolated dephostatin from Streptomyces as a novel inhibitor of CD45
      associated protein-tyrosine phosphatase. We prepared Et-3,4-dephostatin as a
      stable analogue and found it to inhibit PTP-1B and SHPTP-1 protein-tyrosine
      phosphatases selectively but not to inhibit CD45 and leukocyte common antigen
      related phosphatase ones effectively. Et-3,4-dephostatin increased the tyrosine
      phosphorylation of the insulin receptor and insulin receptor substrate-1 with or
      without insulin in differentiated 3T3-L1 mouse adipocytes. The increase of
      tyrosine phosphorylation by Et-3,4-dephostatin was more prominent in 6-h than in
      30-min incubation. It also increased phosphorylation and activation of Akt with
      or without insulin. Et-3,4-dephostatin also enhanced translocation of glucose
      transporter 4 from the cytoplasm to the membrane and 2-deoxy-glucose transport.
      Et-3,4-dephostatin-induced glucose uptake was inhibited by SB203580, a p38
      inhibitor, but not by PD98059, a MEK inhibitor, or by cycloheximide as insulin
      induced uptake. Interestingly, although LY294002, a phosphatidylinositol 3-kinase
      inhibitor, inhibited the insulin-induced glucose uptake completely, it only
      partially inhibited the Et-3,4-dephostatin-induced uptake. It also blocked
      insulin-induced glucose transporter 4 translocation but not the Et-3,4
      dephostatin-induced one. The increase in c-Cbl tyrosine phosphorylation caused by
      Et-3,4-dephostatin was stronger than that in insulin receptor phosphorylation.
      These observations indicate that a phosphatidylinositol 3-kinase-independent
      pathway involving c-Cbl is more important in Et-3,4-dephostatin-induced glucose
      uptake than in insulin-induced uptake. Et-3,4-dephostatin showed an in vivo
      antidiabetic effect in terms of reducing the high blood glucose level in KK-A(y)
      mice after oral administration. Thus, Et-3,4-dephostatin potentiated insulin
      related signal transductions in cultured mouse adipocytes and showed an
      antidiabetic effect in mice.

PMID- 11342533
TI  - Expression of the oligomerization domain of the replication-associated protein
      (Rep) of Tomato leaf curl New Delhi virus interferes with DNA accumulation of
      heterologous geminiviruses.
AB  - The minimal DNA binding domain of the replication-associated protein (Rep) of
      Tomato leaf curl New Delhi virus was determined by electrophoretic mobility gel
      shift analysis and co-purification assays. DNA binding activity maps to amino
      acids 1-160 (Rep-(1-160)) of the Rep protein and overlaps with the protein
      oligomerization domain. Transient expression of Rep protein (Rep-(1-160)) was
      found to inhibit homologous viral DNA accumulation by 70-86% in tobacco
      protoplasts and in Nicotiana benthamiana plants. The results obtained showed that
      expression of N-terminal sequences of Rep protein could efficiently interfere
      with DNA binding and oligomerization activities during virus infection.
      Surprisingly, this protein reduced accumulation of the African cassava mosaic
      virus, Pepper huasteco yellow vein virus and Potato yellow mosaic virus by 22
      48%. electrophoretic mobility shift assays and co-purification studies showed
      that Rep-(1-160) did not bind with high affinity in vitro to the corresponding
      common region sequences of heterologous geminiviruses. However, Rep-(1-160)
      formed oligomers with the Rep proteins of the other geminiviruses. These data
      suggest that the regulation of virus accumulation may involve binding of the Rep
      to target DNA sequences and to the other Rep molecules during virus replication.

PMID- 11342534
TI  - Cholesterol-dependent formation of GM1 ganglioside-bound amyloid beta-protein, an
      endogenous seed for Alzheimer amyloid.
AB  - GM1 ganglioside-bound amyloid beta-protein (GM1/Abeta), found in brains
      exhibiting early pathological changes of Alzheimer's disease (AD) including
      diffuse plaques, has been suggested to be involved in the initiation of amyloid
      fibril formation in vivo by acting as a seed. To elucidate the molecular
      mechanism underlying GM1/Abeta formation, the effects of lipid composition on the
      binding of Abeta to GM1-containing lipid bilayers were examined in detail using
      fluorescent dye-labeled human Abeta-(1-40). Increases in not only GM1 but also
      cholesterol contents in the lipid bilayers facilitated the binding of Abeta to
      the membranes by altering the binding capacity but not the binding affinity. An
      increase in membrane-bound Abeta concentration triggered its conformational
      transition from helix-rich to beta-sheet-rich structures. Excimer formation of
      fluorescent dye-labeled GM1 suggested that Abeta recognizes a GM1 "cluster" in
      membranes, the formation of which is facilitated by cholesterol. The results of
      the present study strongly suggested that increases in intramembrane cholesterol
      content, which are likely to occur during aging, appear to be a risk factor for
      amyloid fibril formation.

PMID- 11342535
TI  - Divergent adaptation of tRNA recognition by Methanococcus jannaschii prolyl-tRNA
      synthetase.
AB  - Analysis of prolyl-tRNA synthetase (ProRS) across all three taxonomic domains
      (Eubacteria, Eucarya, and Archaea) reveals that the sequences are divided into
      two distinct groups. Recent studies show that Escherichia coli ProRS, a member of
      the "prokaryotic-like" group, recognizes specific tRNA bases at both the acceptor
      and anticodon ends, whereas human ProRS, a member of the "eukaryotic-like" group,
      recognizes nucleotide bases primarily in the anticodon. The archaeal
      Methanococcus jannaschii ProRS is a member of the eukaryotic-like group, although
      its tRNA(Pro) possesses prokaryotic features in the acceptor stem. We show here
      that, in some respects, recognition of tRNA(Pro) by M. jannaschii ProRS parallels
      that of human, with a strong emphasis on the anticodon and only weak recognition
      of the acceptor stem. However, our data also indicate differences in the details
      of the anticodon recognition between these two eukaryotic-like synthetases.
      Although the human enzyme places a stronger emphasis on G35, the M. jannaschii
      enzyme places a stronger emphasis on G36, a feature that is shared by E. coli
      ProRS. These results, interpreted in the context of an extensive sequence
      alignment, provide evidence of divergent adaptation by M. jannaschii ProRS;
      recognition of the tRNA acceptor end is eukaryotic-like, whereas the details of
      the anticodon recognition are prokaryotic-like. This divergence may be a
      reflection of the unusual dual function of this enzyme, which catalyzes specific
      aminoacylation with proline as well as with cysteine.

PMID- 11342536
TI  - Terminal minihelix, a novel RNA motif that directs polymerase III transcripts to
      the cell cytoplasm. Terminal minihelix and RNA export.
AB  - Determining the cis-acting elements controlling nuclear export of RNA is
      critical, because they specify which RNA will be selected for transport. We have
      characterized the nuclear export motif of the adenoviral VA1 RNA, a small
      cytoplasmic RNA transcribed by RNA polymerase III. Using a large panel of VA1
      mutants in both transfected COS cells and injected Xenopus oocytes, we showed
      that the terminal stem of VA1 is necessary and sufficient for its export.
      Surprisingly, we found that the nucleotide sequence within the terminal stem is
      not important. Rather, the salient features of this motif are its length and its
      relative position within the RNA. Such stems thus define a novel and degenerate
      cytoplasmic localization motif that we termed the minihelix. This motif is found
      in a variety of polymerase III transcripts, and cross-competition analysis in
      Xenopus oocytes revealed that export of one such RNA, like hY1 RNA, is
      specifically competed by VA1 or artificial minihelix. Taken together these
      results show that the minihelix defines a new cis-acting export element and that
      this motif could be exported via a novel and specific nuclear export pathway.

PMID- 11342537
TI  - Induction of the phospholipid transfer protein gene accounts for the high density
      lipoprotein enlargement in mice treated with fenofibrate.
AB  - Fibrate treatment in mice is known to modulate high density lipoprotein (HDL)
      metabolism by regulating apolipoprotein (apo)AI and apoAII gene expression. In
      addition to alterations in plasma HDL levels, fibrates induce the emergence of
      large, cholesteryl ester-rich HDL in treated transgenic mice expressing human
      apoAI (HuAITg). The mechanisms of these changes may not be restricted to the
      modulation of apolipoprotein gene expression, and the aim of the present study
      was to determine whether the expression of factors known to affect HDL metabolism
      (i.e. phospholipid transfer protein (PLTP), lecithin:cholesterol acyltransferase,
      and hepatic lipase) are modified in fenofibrate-treated mice. Significant rises
      in plasma PLTP activity were observed after 2 weeks of fenofibrate treatment in
      both wild-type and HuAITg mice. Simultaneously, hepatic PLTP mRNA levels
      increased in a dose-dependent fashion. In contrast to PLTP, lecithin:cholesterol
      acyltransferase mRNA levels in HuAITg mice were not significantly modified by
      fenofibrate despite a significant decrease in plasma cholesterol esterification
      activity. Fenofibrate did not induce any change in hepatic lipase activity.
      Fenofibrate significantly increased HDL size, an effect that was more pronounced
      in HuAITg mice than in wild-type mice. This effect in wild-type mice was
      completely abolished in PLTP-deficient mice. Finally, fenofibrate treatment did
      not influence PLTP activity or hepatic mRNA in peroxisome proliferator-activated
      receptor-alpha-deficient mice. It is concluded that 1) fenofibrate treatment
      increases plasma phospholipid transfer activity as the result of up-regulation of
      PLTP gene expression through a peroxisome proliferator-activated receptor-alpha
      dependent mechanism, and 2) increased plasma PLTP levels account for the marked
      enlargement of HDL in fenofibrate-treated mice.

PMID- 11342538
TI  - Nuclear import/export of hRPF1/Nedd4 regulates the ubiquitin-dependent
      degradation of its nuclear substrates.
AB  - The ubiquitin-protein ligase (E3), hRPF1/Nedd4, is a component of the ubiquitin
      proteasome pathway responsible for substrate recognition and specificity.
      Although previously characterized as a regulator of the stability of cytoplasmic
      proteins, hRPF1/Nedd4 has also been suggested to have a role in the nucleus.
      However, in light of the cytoplasmic localization of hRPF1/Nedd4, it is unclear
      whether bona fide nuclear substrates of hRPF1/Nedd4 exist, and if so, what
      mechanism may allow a cytoplasmic ubiquitin ligase to manifest nuclear activity.
      Our search for nuclear substrates led to the identification of the human proline
      rich transcript, brain-expressed (hPRTB) protein, the ubiquitination and
      degradation of which is regulated by hRPF1/Nedd4. Interestingly, hPRTB
      colocalizes with the splicing factor SC35 in nuclear speckles. Finally, we
      demonstrate that hRPF1/Nedd4 is indeed capable of entering the nucleus; however,
      the presence of a functional Rev-like nuclear export sequence in hRPF1/Nedd4
      ensures a predominant cytoplasmic localization. Cumulatively, these findings
      highlight a nuclear role for the ubiquitin ligase hRPF1/Nedd4 and underscore
      cytoplasmic/nuclear localization as an important regulatory component of
      hRPF1/Nedd4-substrate recognition.

PMID- 11342539
TI  - Proteolytic cleavage of chromogranin A (CgA) by plasmin. Selective liberation of
      a specific bioactive CgA fragment that regulates catecholamine release.
AB  - Chromogranin A (CgA), the major soluble protein in catecholamine storage
      vesicles, serves as a prohormone that is cleaved into bioactive peptides that
      inhibit catecholamine release, providing an autocrine, negative feedback
      mechanism for regulating catecholamine responses during stress. However, the
      proteases responsible for the processing of CgA and release of bioactive peptides
      have not been established. Recently, we found that chromaffin cells express
      components of the plasmin(ogen) system, including tissue plasminogen activator,
      which is targeted to catecholamine storage vesicles and released with CgA and
      catecholamines in response to sympathoadrenal stimulation, and high affinity cell
      surface receptors for plasminogen, to promote plasminogen activation at the cell
      surface. In the present study, we investigated processing of CgA by plasmin and
      sought to identify specific bioactive CgA peptides produced by plasmin
      proteolysis. Highly purified human CgA (hCgA) was produced by expression in
      Escherichia coli and purification using metal affinity chromatography. hCgA was
      digested with plasmin. Matrix-assisted laser desorption/ionization mass
      spectrometry identified a major peptide produced with a mass/charge ratio (m/z)
      of 1546, corresponding uniquely to hCgA-(360-373), the identity of which was
      confirmed by reverse phase high pressure liquid chromatography and amino-terminal
      microsequencing. hCgA-(360-373) was selectively liberated by plasmin from hCgA at
      early time points and was stable even after prolonged exposure to plasmin. The
      corresponding synthetic peptide markedly inhibited nicotine-induced catecholamine
      release from pheochromocytoma cells. These results identify plasmin as a
      protease, present in the local environment of the chromaffin cell, that
      selectively cleaves CgA to generate a bioactive fragment, hCgA-(360-373), that
      inhibits nicotinic-mediated catecholamine release. These results suggest that the
      plasminogen/plasmin system through its interaction with CgA may play a major role
      in catecholaminergic function and suggest a specific mechanism as well as a
      discrete CgA peptide through which this effect is mediated.

PMID- 11342540
TI  - Urokinase induces expression of its own receptor in Beas2B lung epithelial cells.
AB  - Interaction between the urokinase-type plasminogen activator (uPA) and its
      receptor (uPAR) localizes cellular proteolysis and promotes cellular
      proliferation and migration. The interaction between uPA and uPAR at the surface
      of epithelial cells thereby contributes to the pathogenesis of lung inflammation
      and neoplasia. In this study, we sought to determine if uPA itself alters uPAR
      expression by lung epithelial cells. uPA enhanced uPAR expression as well as
      (125)I-uPA binding in Beas2B lung epithelial cells in a time- and concentration
      dependent manner. The uPA-mediated induction of uPAR is not accomplished through
      its receptor and requires enzymatic activity. The low molecular weight fragment
      of uPA, lacking the receptor binding domain, was as potent as intact two-chain
      uPA in inducing expression of uPAR at the cell surface. Plasmin, the end product
      of plasminogen activation, did not alter uPA-mediated uPAR expression. Induction
      of uPAR by uPA represents a novel pathway by which epithelial cells can regulate
      uPAR-dependent cellular responses that may contribute to stromal remodeling in
      lung injury or neoplasia.

PMID- 11342541
TI  - Analysis of fertilin alpha (ADAM1)-mediated sperm-egg cell adhesion during
      fertilization and identification of an adhesion-mediating sequence in the
      disintegrin-like domain.
AB  - Fertilin alpha (also known as ADAM1) is a member of the ADAM (A disintegrin and A
      metalloprotease domain) family of proteins. In this study, we examine the
      mechanism of mouse fertilin alpha's in adhesion of sperm to the egg plasma
      membrane during fertilization. We find that recombinant forms of fertilin alpha
      corresponding to either the disintegrin-like domain or the cysteine-rich domain
      and the EGF-like repeat can perturb sperm-egg binding, suggesting that both of
      these domains can participate in fertilin alpha-mediated adhesion events. In
      further examination of the fertilin alpha disintegrin-like domain, we find that a
      subdomain of disintegrin-like domain with the sequence DLEECDCG outside the
      putative disintegrin loop but with homology to the fertilin beta disintegrin loop
      can inhibit the binding of both sperm and recombinant fertilin alpha to eggs,
      suggesting that this is an adhesion-mediating motif of the fertilin alpha
      disintegrin-like domain. This sequence also inhibits the binding of recombinant
      fertilin beta to eggs and thus is the first peptide sequence found to block two
      different sperm ligands. Finally, a monoclonal antibody to the tetraspanin
      protein CD9, KMC.8, inhibited the binding of recombinant fertilin alpha to eggs
      in one type of binding assay, suggesting that, under certain conditions, fertilin
      alpha may interact with a KMC.8-sensitive binding site on the egg plasma
      membrane.

PMID- 11342542
TI  - Alternative splicing regulates the endoplasmic reticulum localization or
      secretion of soluble secreted endopeptidase.
AB  - A subfamily of zinc metalloproteases, represented by Neutral endopeptidase (EC )
      and endothelin-converting enzyme, is involved in the metabolism of a variety of
      biologically active peptides. Recently, we cloned and characterized a novel
      member of this metalloprotease family termed soluble secreted endopeptidase
      (SEP), which hydrolyzes many vasoactive peptides. Here we report that alternative
      splicing of the mouse SEP gene generates two polypeptides, SEP(Delta) and SEP.
      After synthesis, both isoforms are inserted into the endoplasmic reticulum (ER)
      as type II membrane proteins. SEP(Delta) then becomes an ER resident, whereas
      SEP, which differs by only the presence of 23 residues at the beginning of its
      luminal domain, is proteolytically cleaved by membrane secretase(s) in the ER and
      transported into the extracellular compartment. An analysis of the chimeric
      proteins between SEP(Delta) and bovine endothelin-converting enzyme-1b (bECE-1b)
      demonstrated that the retention of SEP(Delta) in the ER is mediated by the
      luminal domain. In addition, the dissection of the chimeric bECE-1b/SEP insertion
      showed that its insertion domain is obviously responsible for its secretion. A
      series of mutagenesis in this region revealed that the minimal requirement for
      cleavage was found to be a WDERTVV motif. Our results suggest that the unique
      subcellular localization and secretion of SEP proteins provide a novel model of
      protein trafficking within the secretory pathway.

PMID- 11342543
TI  - A novel heat shock protein plays an important role in thermal stress management
      in cyanobacteria.
AB  - A novel heat shock gene, orf7.5, which encodes a putative acidic polypeptide of
      63 amino acids, was cloned from the cyanobacterium Synechococcus sp. PCC 7942.
      Northern blot analysis revealed the presence of 400- and 330-base orf7.5 mRNAs,
      which were barely detectable in the cells grown at 30 degrees C but increased
      transiently in response to heat shock at 40 or 45 degrees C. Primer extension
      analysis showed that the two mRNAs have different 5'-ends. Chloramphenicol
      enhanced the accumulation of the orf7.5 mRNA, whereas it inhibited the increase
      in the amount of the groESL mRNA. To reveal the role of the orf7.5 gene in
      thermal stress management, we constructed a stable mutant in which a gene
      conferring resistance to an antibiotic was inserted into the coding region of the
      orf7.5 gene. The interruption led to a marked inhibition of growth at 45 degrees
      C and a decrease in the basal and acquired thermo-tolerances at 50 degrees C in
      the transformants, indicating that the gene plays a role in thermal stress
      management. The orf7.5 mutant could be complemented with a return to the wild
      type phenotype by a DNA fragment containing orf7.5 but not by mutated orf7.5s, in
      which a nonsense mutation was generated by introducing a frameshift or a point
      mutation within the orf7.5-coding region. Thus, thermo-tolerance requires an
      appropriate translation product, not simply a transcript. Accumulation of the
      groESL transcript in the orf7.5 mutant was strongly reduced, suggesting that the
      orf7.5 gene product controls the expression of the groESL operon.

PMID- 11342544
TI  - Quaternary structure and metal ion requirement of family II pyrophosphatases from
      Bacillus subtilis, Streptococcus gordonii, and Streptococcus mutans.
AB  - Pyrophosphatase (PPase) from Bacillus subtilis has recently been found to be the
      first example of a family II soluble PPase with a unique requirement for Mn2+. In
      the present work, we cloned and overexpressed in Escherichia coli putative genes
      for two more family II PPases (from Streptococcus mutans and Streptococcus
      gordonii), isolated the recombinant proteins, and showed them to be highly
      specific and active PPases (catalytic constants of 1700-3300 s(-)1 at 25 degrees
      C in comparison with 200-400 s(-)1 for family I). All three family II PPases were
      found to be dimeric manganese metalloenzymes, dissociating into much less active
      monomers upon removal of Mn2+. The dimers were found to have one high affinity
      manganese-specific site (K(d) of 0.2-3 nm for Mn2+ and 10-80 microm for Mg2+) and
      two or three moderate affinity sites (K(d) approximately 1 mm for both cations)
      per subunit. Mn2+ binding to the high affinity site, which occurs with a half
      time of less than 10 s at 1.5 mm Mn2+, dramatically shifts the monomer <--> dimer
      equilibrium in the direction of the dimer, further activates the dimer, and
      allows substantial activity (60-180 s(-)1) against calcium pyrophosphate, a
      potent inhibitor of family I PPases.

PMID- 11342545
TI  - Endothelin-1 induces serine phosphorylation of the adaptor protein p66Shc and its
      association with 14-3-3 protein in glomerular mesangial cells.
AB  - Endothelin-1 (ET-1) is a vasoconstrictor peptide known to be a potent mitogen for
      glomerular mesangial cells (GMC). In the current study, it is demonstrated that
      ET-1 treatment of GMC results in serine phosphorylation of the 66-kDa isoform of
      the adapter protein Shc (p66(Shc)). ET-1-induced serine phosphorylation of
      p66(Shc) requires activation of the mitogen-activated protein kinase
      (MAPK)/extracellular signal-regulated kinase (ERK) signaling module and is
      efficiently inhibited by both a MAPK/ERK kinase (MEK)-selective inhibitor and
      adenovirus-mediated transfer of a dominant interfering MEK1 mutant. Furthermore,
      adenovirus-mediated transfer of a constitutively active MEK1 mutant was found to
      markedly increase p66(Shc) serine phosphorylation. Adenoviruses encoding
      constitutively active mutants of MAPK kinases 3 and 6 (upstream kinases of
      p38(MAPK)) and 7 (upstream kinase of c-Jun NH(2)-terminal kinase) failed to
      induce serine phosphorylation of this adaptor protein. Serine phosphorylation of
      p66(Shc) resulted in its association with the serine binding motif-containing
      protein 14-3-3. ET-1-induced phosphorylation of a serine encompassed in the 14-3
      3 binding motif of p66(Shc) was confirmed in experiments employing anti-phospho
      14-3-3 binding motif antibodies. These studies are the first to demonstrate that
      G protein-coupled receptors stimulate serine phosphorylation of p66(Shc) and the
      first to report the formation of a signaling complex between p66(Shc) and 14-3-3.

PMID- 11342546
TI  - Alloxan-induced mitochondrial permeability transition triggered by calcium, thiol
      oxidation, and matrix ATP.
AB  - In addition to their critical function in energy metabolism, mitochondria contain
      a permeability transition pore, which is regulated by adenine nucleotides. We
      investigated conditions required for ATP to induce a permeability transition in
      mammalian mitochondria. Mitochondrial swelling associated with mitochondria
      permeability transition (MPT) was initiated by adding succinate to a rat liver
      mitochondrial suspension containing alloxan, a diabetogenic agent. If alloxan was
      added immediately with or 5 min after adding succinate, MPT was strikingly
      decreased. MPT induced by alloxan was inhibited by EGTA and several agents
      causing thiol oxidation, suggesting that alloxan leads to permeability transition
      through a mechanism dependent on Ca(2+) uptake and sulfhydryl oxidation.
      Antimycin A and cyanide, inhibitors of electron transfer, carbonyl cyanide m
      chlorophenylhydrazone, and oligomycin all inhibited MPT. During incubation with
      succinate, alloxan depleted ATP in mitochondria after an initial transient
      increase. However, in a mitochondrial suspension containing EGTA, ATP
      significantly increased in the presence of alloxan to a level greater than that
      of the control. These results suggest the involvement of energized transport of
      Ca(2+) in the MPT initiation. Addition of exogenous ATP, however, did not trigger
      MPT in the presence of alloxan and had no effect on MPT induced by alloxan. We
      conclude that alloxan-induced MPT requires mitochondrial energization, oxidation
      of protein thiols, and matrix ATP to promote energized uptake of Ca(2+).

PMID- 11342547
TI  - Antigen specificity and high affinity binding provided by one single loop of a
      camel single-domain antibody.
AB  - Detailed knowledge on antibody-antigen recognition is scarce given the unlimited
      antibody specificities of which only few have been investigated at an atomic
      level. We report the crystal structures of an antibody fragment derived from a
      camel heavy chain antibody against carbonic anhydrase, free and in complex with
      antigen. Surprisingly, this single-domain antibody interacts with nanomolar
      affinity with the antigen through its third hypervariable loop (19 amino acids
      long), providing a flat interacting surface of 620 A(2). For the first time, a
      single-domain antibody is observed with its first hypervariable loop adopting a
      type-1 canonical structure. The second hypervariable loop, of unique size due to
      a somatic mutation, reveals a regular beta-turn. The third hypervariable loop
      covers the remaining hypervariable loops and the side of the domain that normally
      interacts with the variable domain of the light chain. Specific amino acid
      substitutions and reoriented side chains reshape this side of the domain and
      increase its hydrophilicity. Of interest is the substitution of the conserved Trp
      103 by Arg because it opens new perspectives to 'humanize' a camel variable
      domain of heavy chain of heavy chain antibody (VHH) or to 'camelize' a human or a
      mouse variable domain of heavy chain of conventional antibody (VH).

PMID- 11342548
TI  - Role of a cluster of hydrophobic residues near the FAD cofactor in Anabaena PCC
      7119 ferredoxin-NADP+ reductase for optimal complex formation and electron
      transfer to ferredoxin.
AB  - In the ferredoxin-NADP(+) reductase (FNR)/ferredoxin (Fd) system, an aromatic
      amino acid residue on the surface of Anabaena Fd, Phe-65, has been shown to be
      essential for the electron transfer (ET) reaction. We have investigated further
      the role of hydrophobic interactions in complex stabilization and ET between
      these proteins by replacing three hydrophobic residues, Leu-76, Leu-78, and Val
      136, situated on the FNR surface in the vicinity of its FAD cofactor. Whereas
      neither the ability of FNR to accept electrons from NADPH nor its structure
      appears to be affected by the introduced mutations, different behaviors with Fd
      are observed. Thus, the ET interaction with Fd is almost completely lost upon
      introduction of negatively charged side chains. In contrast, only subtle changes
      are observed upon conservative replacement. Introduction of Ser residues produces
      relatively sizable alterations of the FAD redox potential, which can explain the
      modified behavior of these mutants. The introduction of bulky aromatic side
      chains appears to produce rearrangements of the side chains at the FNR/Fd
      interaction surface. Thus, subtle changes in the hydrophobic patch influence the
      rates of ET to and from Fd by altering the binding constants and the FAD redox
      potentials, indicating that these residues are especially important in the
      binding and orientation of Fd for efficient ET. These results are consistent with
      the structure reported for the Anabaena FNR.Fd complex.

PMID- 11342549
TI  - A novel nucleolar protein, NIFK, interacts with the forkhead associated domain of
      Ki-67 antigen in mitosis.
AB  - In a previous study, we demonstrated that the forkhead associated (FHA) domain of
      pKi-67 interacts with the novel kinesin-like protein, Hklp2 (Sueishi, M., Takagi,
      M., and Yoneda, Y. (2000) J. Biol. Chem. 275, 28888-28892). In this study, we
      report on the identification of a putative RNA-binding protein of 293 residues as
      another binding partner of the FHA domain of pKi-67 (referred to as NIFK for
      nucleolar protein interacting with the FHA domain of pKi-67). Human NIFK (hNIFK)
      interacted with the FHA domain of pKi-67 (Ki-FHA) efficiently in vitro when hNIFK
      was derived from mitotically arrested cells. In addition, a moiety of hNIFK was
      co-localized with pKi-67 at the peripheral region of mitotic chromosomes. The
      hNIFK domain that interacts with Ki-FHA was mapped in the yeast two-hybrid system
      to a portion encompassed by residues 226-269. In a binding assay utilizing
      Xenopus egg extracts, it was found that the mitosis-specific environment and two
      threonine residues within this portion of hNIFK (Thr-234 and Thr-238) were
      crucial for the efficient interaction of hNIFK and Ki-FHA, suggesting that hNIFK
      interacts with Ki-FHA in a mitosis-specific and phosphorylation-dependent manner.
      These findings provide a new clue to our understanding of the cellular function
      of pKi-67.

PMID- 11342550
TI  - A central functional role for the 49-kDa subunit within the catalytic core of
      mitochondrial complex I.
AB  - We have analyzed a series of eleven mutations in the 49-kDa protein of
      mitochondrial complex I (NADH:ubiquinone oxidoreductase) from Yarrowia lipolytica
      to identify functionally important domains in this central subunit. The mutations
      were selected based on sequence homology with the large subunit of [NiFe]
      hydrogenases. None of the mutations affected assembly of complex I, all decreased
      or abolished ubiquinone reductase activity. Several mutants exhibited decreased
      sensitivities toward ubiquinone-analogous inhibitors. Unexpectedly, seven
      mutations affected the properties of iron-sulfur cluster N2, a prosthetic group
      not located in the 49-kDa subunit. In three of these mutants cluster N2 was not
      detectable by electron-paramagnetic resonance spectroscopy. The fact that the
      small subunit of hydrogenase is homologous to the PSST subunit of complex I
      proposed to host cluster N2 offers a straightforward explanation for the
      observed, unforeseen effects on this iron-sulfur cluster. We propose that the
      fold around the hydrogen reactive site of [NiFe] hydrogenase is conserved in the
      49-kDa subunit of complex I and has become part of the inhibitor and ubiquinone
      binding region. We discuss that the fourth ligand of iron-sulfur cluster N2
      missing in the PSST subunit may be provided by the 49-kDa subunit.

PMID- 11342551
TI  - Replication protein A in Pyrococcus furiosus is involved in homologous DNA
      recombination.
AB  - Single-stranded DNA-binding protein in Bacteria and replication protein A (RPA)
      in Eukarya play crucial roles in DNA replication, repair, and recombination
      processes. We identified an RPA complex from the hyperthermophilic archaeon,
      Pyrococcus furiosus. Unlike the single-peptide RPAs from the methanogenic
      archaea, Methanococcus jannaschii and Methanothermobacter thermoautotrophicus, P.
      furiosus RPA (PfuRPA) exists as a stable hetero-oligomeric complex consisting of
      three subunits, RPA41, RPA14, and RPA32. The amino acid sequence of RPA41 has
      some similarity to those of the eukaryotic RPA70 subunit and the M. jannaschii
      RPA. On the other hand, RPA14 and RPA32 do not share homology with any known open
      reading frames from Bacteria and Eukarya. However, six of eight archaea, whose
      total genome sequences have been published, have the open reading frame
      homologous to RPA32. The PfuRPA complex, but not each subunit alone, specifically
      bound to a single-stranded DNA and clearly enhanced the efficiency of an in vitro
      strand-exchange reaction by the P. furiosus RadA protein. Moreover,
      immunoprecipitation analyses showed that PfuRPA interacts with the recombination
      proteins, RadA and Hjc, as well as replication proteins, DNA polymerases,
      primase, proliferating cell nuclear antigen, and replication factor C in P.
      furiosus cells. These results indicate that PfuRPA plays important roles in the
      homologous DNA recombination in P. furiosus.

PMID- 11342552
TI  - Interaction of human pancreatic ribonuclease with human ribonuclease inhibitor.
      Generation of inhibitor-resistant cytotoxic variants.
AB  - Mammalian ribonucleases interact very strongly with the intracellular
      ribonuclease inhibitor (RI). Eukaryotic cells exposed to mammalian ribonucleases
      are protected from their cytotoxic action by the intracellular inhibition of
      ribonucleases by RI. Human pancreatic ribonuclease (HPR) is structurally and
      functionally very similar to bovine RNase A and interacts with human RI with a
      high affinity. In the current study, we have investigated the involvement of Lys
      7, Gln-11, Asn-71, Asn-88, Gly-89, Ser-90, and Glu-111 in HPR in its interaction
      with human ribonuclease inhibitor. These contact residues were mutated either
      individually or in combination to generate mutants K7A, Q11A, N71A, E111A, N88R,
      G89R, S90R, K7A/E111A, Q11A/E111A, N71A/E111A, K7A/N71A/E111A, Q11A/N71A/E111A,
      and K7A/Q11A/N71A/E111A. Out of these, eight mutants, K7A, Q11A, N71A, S90R,
      E111A, Q11A/E111A, N71A/E111A, and K7A/N71A/E111A, showed an ability to evade RI
      more than the wild type HPR, with the triple mutant K7A/N71A/E111A having the
      maximum RI resistance. As a result, these variants exhibited higher cytotoxic
      activity than wild type HPR. The mutation of Gly-89 in HPR produced no change in
      the sensitivity of HPR for RI, whereas it has been reported that mutating the
      equivalent residue Gly-88 in RNase A yielded a variant with increased RI
      resistance and cytotoxicity. Hence, despite its considerable homology with RNase
      A, HPR shows differences in its interaction with RI. We demonstrate that
      interaction between human pancreatic ribonuclease and RI can be disrupted by
      mutating residues that are involved in HPR-RI binding. The inhibitor-resistant
      cytotoxic HPR mutants should be useful in developing therapeutic molecules.

PMID- 11342553
TI  - Differential usage of signal transduction pathways defines two types of serum
      response factor target gene.
AB  - Activation of the transcription factor serum response factor (SRF) is dependent
      on Rho-controlled changes in actin dynamics. We used pathway-specific inhibitors
      to compare the roles of actin dynamics, extracellular signal-regulated kinase
      (ERK) signaling, and phosphatidylinositol 3-kinase in signaling either to SRF
      itself or to four cellular SRF target genes. Serum, lysophosphatidic acid,
      platelet-derived growth factor, and phorbol 12-myristate 13-acetate (PMA) each
      activated transcription of a stably integrated SRF reporter gene dependent on
      functional RhoA GTPase. Inhibition of mitogen-activated protein kinase-ERK kinase
      (MEK) signalling reduced activation of the SRF reporter by all stimuli by about
      50%, except for PMA, which was effectively blocked. Inhibition of
      phosphatidylinositol 3-kinase slightly reduced reporter activation by serum and
      lysophosphatidic acid but substantially inhibited activation by platelet-derived
      growth factor and PMA. Reporter induction by all stimuli was absolutely dependent
      on actin dynamics. Regulation of the SRF (srf) and vinculin (vcl) genes was
      similar to that of the SRF reporter gene; activation by all stimuli was Rho
      dependent and required actin dynamics but was largely independent of MEK
      activity. In contrast, activation of fos and egr1 occurred independently of RhoA
      and actin polymerization but was almost completely dependent on MEK activation.
      These results show that at least two classes of SRF target genes can be
      distinguished on the basis of their relative sensitivity to RhoA-actin and MEK
      ERK signaling pathways.

PMID- 11342554
TI  - Structural characterization of the Pseudomonas aeruginosa 1244 pilin glycan.
AB  - An antigenic similarity between lipopolysaccharide (LPS) and glycosylated pilin
      of Pseudomonas aeruginosa 1244 was noted. We purified a glycan-containing
      molecule from proteolytically digested pili and showed it to be composed of three
      sugars and serine. This glycan competed with pure pili and LPS for reaction with
      an LPS-specific monoclonal antibody, which also inhibited twitching motility by
      P. aeruginosa bearing glycosylated pili. One-dimensional NMR analysis of the
      glycan indicated the sugars to be 5N beta OHC(4)7NfmPse, Xyl, and FucNAc. The
      complete proton assignments of these sugars as well as the serine residue were
      determined by COSY and TOCSY. Electrospray ionization mass spectrometry (MS)
      determined the mass of this molecule to be 771.5. The ROESY NMR spectrum, tandem
      MS/MS analysis, and methylation analysis provided information on linkage and the
      sequence of oligosaccharide components. These data indicated that the molecule
      had the following structure: alpha-5N beta OHC(4)7NFmPse-(2-->4)beta-Xyl-(1-->3)
      beta-FucNAc-(1-->3)-beta-Ser.

PMID- 11342555
TI  - Beta-amino acid scan of a class I major histocompatibility complex-restricted
      alloreactive T-cell epitope.
AB  - An HLA-B27-restricted self-octapeptide known to react with an alloreactive T-cell
      receptor has been modified by systematic substitution of a beta-amino acid for
      the natural alpha-amino acid residue, over the whole length of the parent
      epitope. All modified peptides were shown to bind to recombinant HLA-B*2705 and
      induce stable major histocompatibility complex-peptide complexes, but with some
      variation depending on the position of the beta-amino acid on the peptide
      sequence. Alteration of the natural peptide sequence at the two N-terminal
      positions (positions 1 and 2) decreases binding affinity and thermodynamic
      stability of the refolded complex, but all other positions (from position 3 to
      the C-terminal residue) were insensitive to the beta-amino acid substitution. All
      modified peptides were recognized by an alloreactive T-cell clone specific for
      the parent epitope with decreased efficiency, to an extent dependent of the
      position that was modified. Furthermore, the introduction of a single beta-amino
      acid at the first two positions of the modified peptide was shown to be
      sufficient to protect them against enzymatic cleavage. Thus, beta-amino acids
      represent new interesting templates for alteration of T-cell epitopes to design
      either synthetic vaccines of T-cell receptor antagonists.

PMID- 11342556
TI  - Contributions of the individual domains in human La protein to its RNA 3'-end
      binding activity.
AB  - The autoantigen La regulates the maturation of RNA polymerase III transcripts by
      binding to their poly(U) termination signal. The modular protein harbors a N
      terminal RNA recognition motif (RRM), RRM1, and in the C-terminal domain, a
      second, atypical RRM2, in addition to a phosphorylation site, and a putative
      nucleotide binding site. This study presents a detailed investigation into the
      RNA 3'-end binding properties of La by using binding titration and competition
      assays with subsequent gel mobility shift analysis. Two truncation mutants
      containing one (La-RRM1) or both (La-RRM1-RRM2) RNA-binding domains were
      constructed, overexpressed, and purified. A K(d) value of 25 +/- 10 nm for La
      binding to a nonameric RNA ligand with the oligouridylate recognition sequence
      was obtained, discriminating with a specificity ratio of approximately 100 for
      this probe over a RNA ligand with a 3'-poly(A) stretch. The N-terminal La-RRM1
      region was identified as the major contributor of these properties to La,
      manifested in a 5-fold lower K(d) of 5 +/- 3 nm and a slightly increased
      specificity ratio of 120 for the RNA ligand. The atypical RRM2 in the C-terminal
      domain of La has an unprecedented negative effect on 3'-end RNA recognition, as
      indicated by a higher K(d) value of 90 +/- 10 nm for the La-RRM1-RRM2 mutant but
      comparable specificity. Thus the C-terminal regions beyond RRM2 positively
      modulate the RNA binding affinity of La. Negative regulation, however, occurs
      through Ser(366) phosphorylation decreasing the binding affinity by 2-fold. ATP
      had no influence on RNA complex formation. The functional implications of these
      findings for the mechanism of action of La are discussed.

PMID- 11342557
TI  - HSP22, a new member of the small heat shock protein superfamily, interacts with
      mimic of phosphorylated HSP27 ((3D)HSP27).
AB  - Most of the members of the superfamily of mammalian small heat shock or stress
      proteins are abundant in muscles where they play a role in muscle function and
      maintenance of muscle integrity. One member of this protein superfamily, human
      HSP27, is rapidly phosphorylated on three serine residues (Ser(15), Ser(78), and
      Ser(82)) during cellular response to a number of extracellular factors. To
      understand better the role of HSP27, we performed a yeast two-hybrid screen of a
      human heart cDNA library for HSP27-interacting proteins. By using the triple
      aspartate mutant, a mimic of phosphorylated HSP27, as "bait" construct, a protein
      with a molecular mass of 21.6 kDa was identified as an HSP27-binding protein.
      Sequence analysis revealed that this new protein shares an overall sequence
      identity of 33% with human HSP27. This protein also contains the alpha-crystallin
      domain in its C-terminal half, a hallmark of the superfamily of small stress
      proteins. Thus, the new protein itself is a member of this protein superfamily,
      and consequently we designated it HSP22. According to the two-hybrid data, HSP22
      interacts preferentially with the triple aspartate form of HSP27 as compared with
      wild-type HSP27. HSP22 is expressed predominantly in muscles. In vitro, HSP22 is
      phosphorylated by protein kinase C (at residues Ser(14) and Thr(63)) and by p44
      mitogen-activated protein kinase (at residues Ser(27) and Thr(87)) but not by
      MAPKAPK-2.

PMID- 11342558
TI  - SOCS-1 protein prevents Janus Kinase/STAT-dependent inhibition of beta cell
      insulin gene transcription and secretion in response to interferon-gamma.
AB  - In the pathogenesis of type I diabetes mellitus, activated leukocytes infiltrate
      pancreatic islets and induce beta cell dysfunction and destruction. Interferon
      (IFN)-gamma, tumor necrosis factor-alpha and interleukin (IL)-1 beta play
      important, although not completely defined, roles in these mechanisms. Here,
      using the highly differentiated beta Tc-Tet insulin-secreting cell line, we
      showed that IFN-gamma dose- and time-dependently suppressed insulin synthesis and
      glucose-stimulated secretion. As described previously IFN-gamma, in combination
      with IL-1 beta, also induces inducible NO synthase expression and apoptosis
      (Dupraz, P., Cottet, S., Hamburger, F., Dolci, W., Felley-Bosco, E., and Thorens,
      B. (2000) J. Biol. Chem. 275, 37672--37678). To assess the role of the Janus
      kinase/signal transducer and activator of transcription (STAT) pathway in IFN
      gamma intracellular signaling, we stably overexpressed SOCS-1 (suppressor of
      cytokine signaling-1) in the beta cell line. We demonstrated that SOCS-1
      suppressed cytokine-induced STAT-1 phosphorylation and increased cellular
      accumulation. This was accompanied by a suppression of the effect of IFN-gamma
      on: (i) reduction in insulin promoter-luciferase reporter gene transcription,
      (ii) decrease in insulin mRNA and peptide content, and (iii) suppression of
      glucose-stimulated insulin secretion. Furthermore, SOCS-1 also suppressed the
      cellular effects that require the combined presence of IL-1 beta and IFN-gamma:
      induction of nitric oxide production and apoptosis. Together our data demonstrate
      that IFN-gamma is responsible for the cytokine-induced defect in insulin gene
      expression and secretion and that this effect can be completely blocked by
      constitutive inhibition of the Janus kinase/STAT pathway.

PMID- 11342559
TI  - Interactions of the rapsyn RING-H2 domain with dystroglycan.
AB  - Rapsyn, a peripheral membrane protein of skeletal muscle, is necessary for the
      formation of the highly organized structure of the vertebrate neuromuscular
      junction. For mice lacking rapsyn, there is a failure of postsynaptic
      specialization characterized by an absence of nicotinic acetylcholine receptors
      (nAChRs) and other integral and peripheral membrane proteins such as beta
      dystroglycan and utrophin. Dystroglycan is necessary for the formation of the
      mature neuromuscular junction and has been shown to interact directly with
      rapsyn. Previous studies with rapsyn fragments and mutants, expressed in 293T
      cells along with nAChRs, establish that the rapsyn tetratricopeptide repeat (TPR)
      domain is involved in self-association and its coiled-coil domain is necessary
      for nAChR clustering. The function of the rapsyn RING-H2 domain, which is not
      necessary for rapsyn self-association or nAChR clustering, is unknown. To further
      characterize these domains, we have used a yeast two-hybrid assay to test for
      interactions at the plasma membrane between rapsyn domains and a nAChR beta
      subunit fragment, the beta-dystroglycan cytoplasmic domain, or rapsyn domains.
      The rapsyn coiled-coil domain interacts with the nAChR beta-subunit cytoplasmic
      domain, but not with itself, other rapsyn domains, or beta-dystroglycan. The RING
      H2 domain interacts only with the beta-dystroglycan cytoplasmic domain.
      Furthermore, when expressed in 293T cells, a rapsyn construct containing as few
      as two TPRs and the RING-H2 domain self-associates and clusters dystroglycan, but
      not nAChRs. These results emphasize the modular character of the rapsyn
      structural domains.

PMID- 11342560
TI  - Specificities for the small G proteins ARF1 and ARF6 of the guanine nucleotide
      exchange factors ARNO and EFA6.
AB  - ARF1 and ARF6 are distant members of the ADP-ribosylation factor (ARF) small G
      protein subfamily. Their distinct cellular functions must result from specificity
      of interaction with different effectors and regulators, including guanine
      nucleotide exchange factors (GEFs). ARF nucleotide-binding site opener (ARNO),
      and EFA6 are analogous ARF-GEFs, both comprising a catalytic "Sec7" domain and a
      pleckstrin homology domain. In vivo ARNO, like ARF1, is mostly cytosolic, with
      minor localizations at the Golgi and plasma membrane; EFA6, like ARF6, is
      restricted to the plasma membrane. However, depending on conditions, ARNO appears
      active on ARF6 as well as on ARF1. Here we analyze the origin of these ARF-GEF
      selectivities. In vitro, in the presence of phospholipid membranes, ARNO
      activates ARF1 preferentially and ARF6 slightly, whereas EFA6 activates ARF6
      exclusively; the stimulation efficiency of EFA6 on ARF6 is comparable with that
      of ARNO on ARF1. These selectivities are determined by the GEFs Sec7 domains
      alone, without the pleckstrin homology and N-terminal domains, and by the ARF
      core domains, without the myristoylated N-terminal helix; they are not modified
      upon permutation between ARF1 and ARF6 of the few amino acids that differ within
      the switch regions. Thus selectivity for ARF1 or ARF6 must depend on subtle
      folding differences between the ARFs switch regions that interact with the Sec7
      domains.

PMID- 11342561
TI  - Uncoupled ATPase activity and heat production by the sarcoplasmic reticulum Ca2+
      ATPase. Regulation by ADP.
AB  - Sarcoplasmic reticulum vesicles of rabbit skeletal muscle accumulate Ca2+ at the
      expense of ATP hydrolysis. The heat released during the hydrolysis of each ATP
      molecule varies depending on whether or not a Ca2+ gradient is formed across the
      vesicle membrane. After Ca2+ accumulation, a part of the Ca2+-ATPase activity is
      not coupled with Ca2+ transport (Yu, X., and Inesi, G. (1995) J. Biol. Chem. 270,
      4361-4367). I now show that both the heat produced during substrate hydrolysis
      and the uncoupled ATPase activity vary depending on the ADP/ATP ratio in the
      medium. With a low ratio, the Ca2+ transport is exothermic, and the formation of
      the gradient increases the amount of heat produced during the hydrolysis of each
      ATP molecule cleaved. With a high ADP/ATP ratio, the Ca2+ transport is
      endothermic, and formation of a gradient increased the amount of heat absorbed
      from the medium. Heat is absorbed from the medium when the Ca2+ efflux is coupled
      with the synthesis of ATP (5.7 kcal/mol of ATP). When there is no ATP synthesis,
      the Ca2+ efflux is exothermic (14-16 kcal/Ca2+ mol). It is concluded that in the
      presence of a low ADP concentration the uncoupled ATPase activity is the dominant
      route of heat production. With a high ADP/ATP ratio, the uncoupled ATPase
      activity is abolished, and the Ca2+ transport is endothermic. The possible
      correlation of these findings with thermogenesis and anoxia is discussed.

PMID- 11342562
TI  - Electrophysiological characterization and ionic stoichiometry of the rat brain
      K(+)-dependent NA(+)/CA(2+) exchanger, NCKX2.
AB  - We have recently described a novel K(+)-dependent Na(+)/Ca(2+) exchanger, NCKX2,
      that is abundantly expressed in brain neurons (Tsoi, M., Rhee, K.-H., Bungard,
      D., Li, X.-F., Lee, S.-L., Auer, R. N., and Lytton, J. (1998) J. Biol. Chem. 273,
      4115--4162). The precise role for NCKX2 in neuronal Ca(2+) homeostasis is not yet
      clearly understood but will depend upon the functional properties of the
      molecule. Here, we have performed whole-cell patch clamp analysis to characterize
      cation dependences and ion stoichiometry for rat brain NCKX2, heterologously
      expressed in HEK293 cells. Outward currents generated by reverse NCKX2 exchange
      depended on external Ca(2+) with a K(12) of 1.4 or 101 microm without or with 1
      mm Mg(2+), and on external K(+) with a K(1/2) of about 12 or 36 mm with choline
      or Li(+) as counter ion, respectively. Na(+) inhibited outward currents with a
      K(1/2) of about 60 mm. Inward currents generated by forward NCKX2 exchange
      depended upon external Na(+) with a K(1/2) of 30 mm and a Hill coefficient of
      2.8. K(+) inhibited the inward currents by a maximum of 40%, with a K(1/2) of 2
      mm or less, depending upon the conditions. The transport stoichiometry of NCKX2
      was determined by observing the change in reversal potential as individual ion
      gradients were altered. Our data support a stoichiometry for rat brain NCKX2 of 4
      Na(+):(1 Ca(2+) + 1 K(+)). These findings provide the first electrophysiological
      characterization of rat brain NCKX2, and the first evidence that a single
      recombinantly expressed NCKX polypeptide encodes a K(+)-transporting Na(+)/Ca(2+)
      exchanger with a transport stoichiometry of 4 Na(+):(1 Ca(2+) + 1 K(+)).

PMID- 11342563
TI  - The second PDZ domain of INAD is a type I domain involved in binding to eye
      protein kinase C. Mutational analysis and naturally occurring variants.
AB  - INAD is a scaffolding protein containing five PSD95/dlg/zonular occludens-1 (PDZ)
      domains that tether NORPA (phospholipase Cbeta(4)), the TRP calcium channel, and
      eye-PKC in Drosophila photoreceptors. We previously showed that eye-PKC
      interacted with the second PDZ domain (PDZ2) of INAD. Sequence comparison with a
      prototypical type I PDZ domain predicts that PDZ2 is the best candidate among the
      five PDZ domains to recognize eye-PKC that contains a type I PDZ ligand, Ile-Thr
      Ile-Ile, at its carboxyl terminus. Replacement of Ile(-3) in eye-PKC with charged
      residues resulted in a drastic reduction of the PDZ2 interaction. Substitution of
      a conserved His with Arg at the second alpha-helix of PDZ2 led to a reduced
      binding; however, a Leu replacement resulted in an enhanced eye-PKC association.
      We isolated and sequenced the InaD gene. The coding sequence of InaD contains
      nine exons spanning 3 kilobases. Translation of coding sequences from three wild
      type alleles revealed three SNPs affecting residues, 282, 319, and 333 of INAD.
      These polymorphisms are localized in PDZ2. Interestingly, we found two of three
      PDZ2 variants displayed a greater affinity for eye-PKC. In summary, we evaluated
      the molecular basis of the eye-PKC and PDZ2 association by mutational analysis
      and concluded that PDZ2 of INAD is a type I domain important for the eye-PKC
      interaction.

PMID- 11342564
TI  - Lithium sensitizes tumor cells in an NF-kappa B-independent way to caspase
      activation and apoptosis induced by tumor necrosis factor (TNF). Evidence for a
      role of the TNF receptor-associated death domain protein.
AB  - We have previously shown that lithium salts can considerably increase the direct
      cytotoxic effect of tumor necrosis factor (TNF) on various tumor cells in vitro
      and in vivo. However, the underlying mechanism has remained largely unknown. Here
      we show that the TNF-sensitizing effect of lithium chloride (LiCl) is independent
      of the type of cell death, either necrosis or apoptosis. In the case of
      apoptosis, TNF/lithium synergism is associated with an enhanced activation of
      caspases and mitochondrial cytochrome c release. Sensitization to apoptosis is
      specific for TNF-induced apoptosis, whereas Fas-mediated or etoposide-induced
      apoptosis remains unaffected. LiCl also potentiates cell death induced by
      artificial oligomerization of a fusion protein between FKBP and the TNF receptor
      associated death domain protein. TNF-induced activation of NF-kappa B-dependent
      gene expression is not modulated by LiCl treatment. These results indicate that
      LiCl enhances TNF-induced cell death in an NF-kappa B-independent way, and
      suggest that the TNF receptor-associated death domain protein plays a crucial
      role in the TNF-sensitizing effect of LiCl.

PMID- 11342565
TI  - SPARC, a matricellular protein that functions in cellular differentiation and
      tissue response to injury.

PMID- 11342566
TI  - Osteopontin as a means to cope with environmental insults: regulation of
      inflammation, tissue remodeling, and cell survival.

PMID- 11342567
TI  - The Ehlers-Danlos syndrome: on beyond collagens.

PMID- 11342568
TI  - The case of CO signaling: why the jury is still out.

PMID- 11342569
TI  - A TWIST in the fate of human osteoblasts identifies signaling molecules involved
      in skull development.

PMID- 11342570
TI  - Cycling with the parathyroid.

PMID- 11342571
TI  - Cytokines and cellular interactions in inflammatory synovitis.

PMID- 11342572
TI  - Reversal of experimental diabetic neuropathy by VEGF gene transfer.
AB  - The pathogenetic basis for diabetic neuropathy has been enigmatic. Using two
      different animal models of diabetes, we have investigated the hypothesis that
      experimental diabetic neuropathy results from destruction of the vasa nervorum
      and can be reversed by administration of an angiogenic growth factor. Nerve blood
      flow, as measured by laser Doppler imaging or direct detection of a locally
      administered fluorescent lectin analogue, was markedly attenuated in rats with
      streptozotocin-induced diabetes, consistent with a profound reduction in the
      number of vessels observed. A severe peripheral neuropathy developed in parallel,
      characterized by significant slowing of motor and sensory nerve conduction
      velocities, compared with nondiabetic control animals. In contrast, 4 weeks after
      intramuscular gene transfer of plasmid DNA encoding VEGF-1 or VEGF-2, vascularity
      and blood flow in the nerves of treated animals were similar to those of
      nondiabetic control rats; constitutive overexpression of both transgenes resulted
      in restoration of large and small fiber peripheral nerve function. Similar
      experiments performed in a rabbit model of alloxan-induced diabetes produced
      comparable results. These findings support the notion that diabetic neuropathy
      results from microvascular ischemia involving the vasa nervorum and suggest the
      feasibility of a novel treatment strategy for patients in whom peripheral
      neuropathy constitutes a secondary complication of diabetes.

PMID- 11342573
TI  - Primary hyperparathyroidism caused by parathyroid-targeted overexpression of
      cyclin D1 in transgenic mice.
AB  - The relationship between abnormal cell proliferation and aberrant control of
      hormonal secretion is a fundamental and poorly understood issue in endocrine cell
      neoplasia. Transgenic mice with parathyroid-targeted overexpression of the cyclin
      D1 oncogene, modeling a gene rearrangement found in human tumors, were created to
      determine whether a primary defect in this cell-cycle regulator can cause an
      abnormal relationship between serum calcium and parathyroid hormone response, as
      is typical of human primary hyperparathyroidism. We also sought to develop an
      animal model of hyperparathyroidism and to examine directly cyclin D1's role in
      parathyroid tumorigenesis. Parathyroid hormone gene regulatory region--cyclin D1
      (PTH--cyclin D1) mice not only developed abnormal parathyroid cell proliferation,
      but also developed chronic biochemical hyperparathyroidism with characteristic
      abnormalities in bone and, notably, a shift in the relationship between serum
      calcium and PTH. Thus, this animal model of human primary hyperparathyroidism
      provides direct experimental evidence that overexpression of the cyclin D1
      oncogene can drive excessive parathyroid cell proliferation and that this
      proliferative defect need not occur solely as a downstream consequence of a
      defect in parathyroid hormone secretory control by serum calcium, as had been
      hypothesized. Instead, primary deregulation of cell-growth pathways can cause
      both the hypercellularity and abnormal control of hormonal secretion that are
      almost inevitably linked together in this common disorder.

PMID- 11342574
TI  - Functional reconstitution, membrane targeting, genomic structure, and chromosomal
      localization of a human urate transporter.
AB  - Elevated serum levels of uric acid have been associated with an increased risk
      for gout, hypertension, cardiovascular disease, and renal failure. The molecular
      mechanisms for the diminished excretion of urate in these disorders, however,
      remain poorly understood. Human galectin 9, which is highly homologous to the rat
      urate transporter rUAT, has been reported to be a secreted or cytosolic protein.
      We provide data that galectin 9 is hUAT, the first identified human urate
      transporter. hUAT is a highly selective urate ion channel when inserted in lipid
      bilayers. When expressed in renal epithelial cells it is an integral plasma
      membrane protein with at least two transmembrane domains. The gene for hUAT
      consists of 11 exons and is mapped to chromosome 17; a highly homologous gene,
      hUAT2, maps to a nearby region of chromosome 17 and is also likely to be a urate
      transporter. hUAT is expressed in a wide variety of tissues and is present in at
      least three isoforms; hUAT2 is less widely expressed at severalfold lower levels
      than hUAT. Further knowledge about the functions of hUAT, its isoforms, and
      hUAT2, as well as mutational analysis of hUAT1 and hUAT2 in individuals or
      families with hyperuricemia, should significantly improve our understanding of
      the molecular mechanisms of urate homeostasis.

PMID- 11342575
TI  - Tissue factor pathway inhibitor-2 is a novel inhibitor of matrix
      metalloproteinases with implications for atherosclerosis.
AB  - Degradation of ECM, particularly interstitial collagen, promotes plaque
      instability, rendering atheroma prone to rupture. Previous studies implicated
      matrix metalloproteinases (MMPs) in these processes, suggesting that dysregulated
      MMP activity, probably due to imbalance with endogenous inhibitors, promotes
      complications of atherosclerosis. We report here that the serine proteinase
      inhibitor tissue factor pathway inhibitor-2 (TFPI-2) can function as an MMP
      inhibitor. TFPI-2 diminished the ability of the interstitial collagenases MMP-1
      and MMP-13 to degrade triple-helical collagen, the primary load-bearing molecule
      of the ECM within human atheroma. In addition, TFPI-2 also reduced the activity
      of the gelatinases MMP-2 and MMP-9. In contrast to the "classical" tissue
      inhibitors of MMPs (TIMPs), TFPI-2 expression in situ correlated inversely with
      MMP levels in human atheroma. TFPI-2 colocalized primarily with smooth muscle
      cells in the normal media as well as the plaque's fibrous cap. Conversely, the
      macrophage-enriched shoulder region, the prototypical site of matrix degradation
      and plaque rupture, stained only weakly for TFPI-2 but intensely for gelatinases
      and interstitial collagenases. Evidently, human mononuclear phagocytes, an
      abundant source of MMPs within human atheroma, lost their ability to express this
      inhibitor during differentiation in vitro. These findings establish a new, anti
      inflammatory function of TFPI-2 of potential pathophysiological significance for
      human diseases, including atherosclerosis.

PMID- 11342576
TI  - Macrophage- and neutrophil-dominant arthritis in human IL-1 alpha transgenic
      mice.
AB  - To study the effects of IL-1 alpha in arthritis, we generated human IL-1 alpha
      (hIL-1 alpha). Transgenic mice expressed hIL-1 alpha mRNA in various organs, had
      high serum levels of hIL-1 alpha, and developed a severe polyarthritic phenotype
      at 4 weeks of age. Not only bone marrow cells but also synoviocytes from knee
      joints produced biologically active hIL-1 alpha. Synovitis started 2 weeks after
      birth, and 8-week-old mice showed hyperplasia of the synovial lining layer, the
      formation of hyperplastic synovium (pannus) and, ultimately, destruction of
      cartilage. Hyperplasia of the synovial lining was due to the accumulation of
      macrophage-like cells expressing F4/80 molecules. hIL-1 alpha was widely
      distributed in macrophage- and fibroblast-like cells of the synovial lining
      cells, as well as synovial fluid monocytes. T and B cells were rare in the
      synovial fluid, and analysis of marker expression suggests that synoviocytes were
      directly histolytic and did not act as antigen-presenting cells. In the joints of
      these mice, we found elevated levels of cells of the monocyte/macrophage and
      granulocyte lineages and of polymorphonuclear neutrophils (PMNs), most of which
      expressed Gr-1, indicating that they were mature, tissue-degrading PMNS: Cultured
      synoviocytes and PMNs from these animals overexpress GM-CSF, suggesting that the
      hematopoietic changes induced by IL-1 and the consequent PMN activation and joint
      destruction are mediated by this cytokine.

PMID- 11342577
TI  - A Glanzmann's mutation in beta 3 integrin specifically impairs osteoclast
      function.
AB  - Osteoclastic bone resorption requires cell-matrix contact, an event mediated by
      the alpha v beta 3 integrin. The structural components of the integrin that
      mediate osteoclast function are, however, not in hand. To address this issue, we
      generated mice lacking the beta 3 integrin gene, which have dysfunctional
      osteoclasts. Here, we show the full rescue of beta 3(-/-) osteoclast function
      following expression of a full-length beta 3 integrin. In contrast, truncated
      beta 3, lacking a cytoplasmic domain (h beta 3c), is completely ineffective in
      restoring function to beta 3(-/-) osteoclasts. To identify the components of the
      beta 3 cytoplasmic domain regulating osteoclast function, we generated six point
      mutants known, in other circumstances, to mediate beta integrin signaling. Of the
      six, only the S(752)P substitution, which also characterizes a form of the human
      bleeding disorder Glanzmann's thrombasthenia, fails to rescue beta 3(-/-)
      osteoclasts or restore ligand-activated signaling in the form of c-src
      activation. Interestingly, the double mutation Y(747)F/Y(759)F, which disrupts
      platelet function, does not affect the osteoclast. Thus similarities and
      distinctions exist in the mechanisms by which the beta 3 integrin regulates
      platelets and osteoclasts.

PMID- 11342578
TI  - Impaired IL-18 processing protects caspase-1-deficient mice from ischemic acute
      renal failure.
AB  - We sought to determine whether mice deficient in the proinflammatory caspase-1,
      which cleaves precursors of IL-1 beta and IL-18, were protected against ischemic
      acute renal failure (ARF). Caspase-1(-/-) mice developed less ischemic ARF as
      judged by renal function and renal histology. These animals had significantly
      reduced blood urea nitrogen and serum creatinine levels and a lower morphological
      tubular necrosis score than did wild-type mice with ischemic ARF. Since caspase-1
      activates IL-18, lack of mature IL-18 might protect these caspase-1(-/-) mice
      from ARF. In wild-type animals, we found that ARF causes kidney IL-18 levels to
      more than double and induces the conversion of the IL-18 precursor to the mature
      form. This conversion is not observed in caspase-1(-/-) ARF mice or sham-operated
      controls. We then injected wild-type mice with IL-18-neutralizing antiserum
      before the ischemic insult and found a similar degree of protection from ARF as
      seen in caspase-1(-/-) mice. In addition, we observed a fivefold increase in
      myeloperoxidase activity in control mice with ARF, but no such increase in
      caspase-1(-/-) or IL-18 antiserum-treated mice. Finally, we confirmed
      histologically that caspase-1(-/-) mice show decreased neutrophil infiltration,
      indicating that the deleterious role of IL-18 in ischemic ARF may be due to
      increased neutrophil infiltration.

PMID- 11342579
TI  - Increased bone formation and decreased osteocalcin expression induced by reduced
      Twist dosage in Saethre-Chotzen syndrome.
AB  - The Saethre-Chotzen syndrome is characterized by premature fusion of cranial
      sutures resulting from mutations in Twist, a basic helix-loop-helix (bHLH)
      transcription factor. We have identified Twist target genes using human mutant
      calvaria osteoblastic cells from a child with Saethre-Chotzen syndrome with a
      Twist mutation that introduces a stop codon upstream of the bHLH domain. We
      observed that Twist mRNA and protein levels were reduced in mutant cells and that
      the Twist mutation increased cell growth in mutant osteoblasts compared with
      control cells. The mutation also caused increased alkaline phosphatase and type I
      collagen expression independently of cell growth. During in vitro osteogenesis,
      Twist mutant cells showed increased ability to form alkaline phosphatase-positive
      bone-like nodular structures associated with increased type I collagen
      expression. Mutant cells also showed increased collagen synthesis and matrix
      production when cultured in aggregates, as well as an increased capacity to form
      a collagenous matrix in vivo when transplanted into nude mice. In contrast, Twist
      mutant osteoblasts displayed a cell-autonomous reduction of osteocalcin mRNA
      expression in basal conditions and during osteogenesis. The data show that
      genetic deletion of Twist causing reduced Twist dosage increases cell growth,
      collagen expression, and osteogenic capability, but inhibits osteocalcin gene
      expression. This provides one mechanism that may contribute to the premature
      cranial ossification induced by deletion of the bHLH Twist domain in Saethre
      Chotzen syndrome.

PMID- 11342580
TI  - Carbon monoxide of vascular origin attenuates the sensitivity of renal arterial
      vessels to vasoconstrictors.
AB  - Rat renal interlobar arteries express heme oxygenase 2 (HO-2) and manufacture
      carbon monoxide (CO), which is released into the headspace gas. CO release falls
      to 30% and 54% of control, respectively, after inhibition of HO activity with
      chromium mesoporphyrin (CrMP) or of HO-2 expression with antisense
      oligodeoxynucleotides (HO-2 AS-ODN). Patch-clamp studies revealed that CrMP
      decreases the open probability of a tetraethylammonium-sensitive (TEA-sensitive)
      105 pS K channel in interlobar artery smooth muscle cells, and that this effect
      of CrMP is reversed by CO. Assessment of phenylephrine-induced tension
      development revealed reduction of the EC(50) in vessels treated with HO-2 AS-ODN,
      CrMP, or TEA. Exogenous CO greatly minimized the sensitizing effect on agonist
      induced contractions of agents that decrease vascular CO production, but not the
      sensitizing effect of K channel blockade with TEA. Collectively, these data
      suggest that vascular CO serves as an inhibitory modulator of vascular reactivity
      to vasoconstrictors via a mechanism that involves a TEA-sensitive K channel.

PMID- 11342581
TI  - Fractalkine (CX3CL1) as an amplification circuit of polarized Th1 responses.
AB  - Fractalkine (FKN, CX3CL1) is a membrane-bound CX3C chemokine induced by primary
      proinflammatory signals in vascular endothelial cells (ECs). Here we examined the
      role of FKN in polarized Th1 or Th2 responses. Proinflammatory signals, including
      LPS, IL-1, TNF, and CD40 ligand, induced FKN, as did IFN-gamma, which had
      synergistic activity with TNF. IL-4 and IL-13 did not stimulate the expression of
      FKN and markedly reduced induction by TNF and IFN-gamma. TNF alone or combined
      with IFN-gamma also induced release of soluble FKN, which was inhibited by IL-4
      and IL-13. In light of this differential regulation of FKN by the master
      cytokines that control polarized responses, we analyzed the interaction of FKN
      with natural killer (NK) cells and polarized T-cell populations. NK cells
      expressed high levels of the FKN receptor CX3CR1 and responded to FKN. CX3CR1 was
      preferentially expressed in Th1 compared with Th2 cells. Th1 but not Th2 cells
      responded to FKN. By immunohistochemistry, FKN was expressed on ECs in psoriasis,
      a Th1-dominated skin disorder, but not in Th2-driven atopic dermatitis.
      Similarly, ECs in Mycobacterium tuberculosis granulomatous lymphadenitis, but not
      those in reactive lymph node hyperplasia or in Castelman's disease, showed
      immunoreactive FKN. These results indicate that regulated expression of FKN in
      ECs participates in an amplification circuit of polarized type I responses.

PMID- 11342582
TI  - Heparin-binding defective lipoprotein lipase is unstable and causes abnormalities
      in lipid delivery to tissues.
AB  - Lipoprotein lipase (LpL) binding to heparan sulfate proteoglycans (HSPGs) is
      hypothesized to stabilize the enzyme, localize LpL in specific capillary beds,
      and route lipoprotein lipids to the underlying tissues. To test these hypotheses
      in vivo, we created mice expressing a human LpL minigene (hLpL(HBM)) carrying a
      mutated heparin-binding site. Three basic amino acids in the carboxyl terminal
      region of LpL were mutated, yielding an active enzyme with reduced heparin
      binding. Mice expressing hLpL(HBM) accumulated inactive human LpL (hLpL) protein
      in preheparin blood. hLpL(HBM) rapidly lost activity during a 37 degrees C
      incubation, confirming a requirement for heparin binding to stabilize LPL:
      Nevertheless, expression of hLpL(HBM) prevented the neonatal demise of LpL
      knockout mice. On the LpL-deficient background hLpL(HBM) expression led to
      defective targeting of lipids to tissues. Compared with mice expressing native
      hLpL in the muscle, hLpL(HBM) transgenic mice had increased postprandial FFAs,
      decreased lipid uptake in muscle tissue, and increased lipid uptake in kidneys.
      Thus, heparin association is required for LpL stability and normal physiologic
      functions. These experiments confirm in vivo that association with HSPGs can
      provide a means to maintain proteins in their stable conformations and to anchor
      them at sites where their activity is required.

PMID- 11342583
TI  - Chronic endothelin-1 treatment leads to heterologous desensitization of insulin
      signaling in 3T3-L1 adipocytes.
AB  - We recently reported that insulin and endothelin-1 (ET-1) can stimulate GLUT4
      translocation via the heterotrimeric G protein G alpha q/11 and through PI3
      kinase--mediated pathways in 3T3-L1 adipocytes. Because both hormones stimulate
      glucose transport through a common downstream pathway, we determined whether
      chronic ET-1 pretreatment would desensitize these cells to acute insulin
      signaling. We found that ET-1 pretreatment substantially inhibited insulin
      stimulated 2-deoxyglucose uptake and GLUT4 translocation. Cotreatment with the
      ETA receptor antagonist BQ 610 prevented these effects, whereas inhibitors of G
      alpha i or G beta gamma were without effect. Chronic ET-1 treatment inhibited
      insulin-stimulated tyrosine phosphorylation of G alpha q/11 and IRS-1, as well as
      their association with PI3-kinase and blocked the activation of PI3-kinase
      activity and phosphorylation of AKT: In addition, chronic ET-1 treatment caused
      IRS-1 degradation, which could be blocked by inhibitors of PI3-kinase or p70 S6
      kinase. Similarly, expression of a constitutively active G alpha q mutant, but
      not the wild-type G alpha q, led to IRS-1 degradation and inhibited insulin
      stimulated phosphorylation of IRS-1, suggesting that the ET-1-induced decrease in
      IRS-1 depends on G alpha q/11 and PI3-kinase. Insulin-stimulated tyrosine
      phosphorylation of SHC was also reduced in ET-1 treated cells, resulting in
      inhibition of the MAPK pathway. In conclusion, chronic ET-1 treatment of 3T3-L1
      adipocytes leads to heterologous desensitization of metabolic and mitogenic
      actions of insulin, most likely through the decreased tyrosine phosphorylation of
      the insulin receptor substrates IRS-1, SHC, and G alpha q/11.

PMID- 11342584
TI  - Testicular damage by microcirculatory disruption and colonization of an immune
      privileged site during Borrelia crocidurae infection.
AB  - The agent of African relapsing fever, Borrelia crocidurae, causes reversible
      multiple organ damage. We hypothesize that this damage is caused when the
      spirochete forms aggregate with erythrocytes in vivo, creating rosettes that plug
      the microcirculatory system. To test this hypothesis, we compared testicular
      microcirculation over an extended time period in two groups of rats: one
      experimentally inoculated with B. crocidurae, the other with the nonerythrocyte
      rosette-forming Borrelia hermsii. In the B. crocidurae group, erythrocyte
      rosettes formed during spiro-chetemia blocked precapillary blood vessels and
      reduced the normal pattern of microcirculatory blood flow. After spirochetemia,
      erythrocyte rosettes disappeared and flow was normalized. Decreased blood flow
      and focal vascular damage with increased permeability and interstitial bleeding
      adjacent to the erythrocyte microemboli induced cell death in seminiferous
      tubules. Interestingly, we found that B. crocidurae could penetrate the tubules
      and remain in the testis long after the end of spirochetemia, suggesting that the
      testis can serve as a reservoir for this bacteria in subsequent relapses. The
      group infected with B. hermsii displayed normal testicular blood flow and
      vasomotion at all selected time points, and suffered no testicular damage. These
      results confirmed our hypothesis that the erythrocyte rosettes produce vascular
      obstruction and are the main cause of histopathology seen in model animal and
      human infections.

PMID- 11342585
TI  - Vascular endothelial growth factor and angiopoietin-1 stimulate postnatal
      hematopoiesis by recruitment of vasculogenic and hematopoietic stem cells.
AB  - Tyrosine kinase receptors for angiogenic factors vascular endothelial growth
      factor (VEGF) and angiopoietin-1 (Ang-1) are expressed not only by endothelial
      cells but also by subsets of hematopoietic stem cells (HSCs). To further define
      their role in the regulation of postnatal hematopoiesis and vasculogenesis, VEGF
      and Ang-1 plasma levels were elevated by injecting recombinant protein or
      adenoviral vectors expressing soluble VEGF(165), matrix-bound VEGF(189), or Ang-1
      into mice. VEGF(165), but not VEGF(189), induced a rapid mobilization of HSCs and
      VEGF receptor (VEGFR)2(+) circulating endothelial precursor cells (CEPs). In
      contrast, Ang-1 induced delayed mobilization of CEPs and HSCs. Combined sustained
      elevation of Ang-1 and VEGF(165) was associated with an induction of
      hematopoiesis and increased marrow cellularity followed by proliferation of
      capillaries and expansion of sinusoidal space. Concomitant to this vascular
      remodeling, there was a transient depletion of hematopoietic activity in the
      marrow, which was compensated by an increase in mobilization and recruitment of
      HSCs and CEPs to the spleen resulting in splenomegaly. Neutralizing monoclonal
      antibody to VEGFR2 completely inhibited VEGF(165), but not Ang-1-induced
      mobilization and splenomegaly. These data suggest that temporal and regional
      activation of VEGF/VEGFR2 and Ang-1/Tie-2 signaling pathways are critical for
      mobilization and recruitment of HSCs and CEPs and may play a role in the
      physiology of postnatal angiogenesis and hematopoiesis.

PMID- 11342586
TI  - The TprK protein of Treponema pallidum is periplasmic and is not a target of
      opsonic antibody or protective immunity.
AB  - The finding that Treponema pallidum, the syphilis spirochete, contains 12
      orthologs of the Treponema denticola outer membrane major sheath protein has
      engendered speculation that members of this T. pallidum repeat (Tpr) family may
      be similarly surface exposed. In this regard, the TprK protein was reported to be
      a target of opsonic antibody and protective immunity and subject to
      immunologically driven sequence variation. Despite these findings, results from
      our previous analyses of treponemal outer membranes in concert with computer
      based predictions for TprK prompted us to examine the cellular location of this
      protein. TprK-alkaline phosphatase fusions expressed in Escherichia coli
      demonstrate that TprK contains a signal peptide. However, opsonophagocytosis
      assays failed to indicate surface exposure of TprK. Moreover, results from three
      independent methodologies, i.e., (a) indirect immunofluorescence analysis of
      agarose-encapsulated organisms, (b) proteinase K treatment of intact spirochetes,
      and (c) Triton X-114 phase partitioning of T. pallidum conclusively demonstrated
      that native TprK is entirely periplasmic. Consistent with this location,
      immunization with the recombinant protein failed to induce either protective
      immunity or select for TprK variants in the rabbit model of experimental
      syphilis. These findings challenge the notion that TprK will be a component of an
      efficacious syphilis vaccine.

PMID- 11342587
TI  - Hypoxia-inducible factor 1-dependent induction of intestinal trefoil factor
      protects barrier function during hypoxia.
AB  - Mucosal organs such as the intestine are supported by a rich and complex
      underlying vasculature. For this reason, the intestine, and particularly barrier
      protective epithelial cells, are susceptible to damage related to diminished
      blood flow and concomitant tissue hypoxia. We sought to identify compensatory
      mechanisms that protect epithelial barrier during episodes of intestinal hypoxia.
      Initial studies examining T84 colonic epithelial cells revealed that barrier
      function is uniquely resistant to changes elicited by hypoxia. A search for
      intestinal-specific, barrier-protective factors revealed that the human
      intestinal trefoil factor (ITF) gene promoter bears a previously unappreciated
      binding site for hypoxia-inducible factor (HIF)-1. Hypoxia resulted in parallel
      induction of ITF mRNA and protein. Electrophoretic mobility shift assay analysis
      using ITF-specific, HIF-1 consensus motifs resulted in a hypoxia-inducible DNA
      binding activity, and loading cells with antisense oligonucleotides directed
      against the alpha chain of HIF-1 resulted in a loss of ITF hypoxia inducibility.
      Moreover, addition of anti-ITF antibody resulted in a loss of barrier function in
      epithelial cells exposed to hypoxia, and the addition of recombinant human ITF to
      vascular endothelial cells partially protected endothelial cells from hypoxia
      elicited barrier disruption. Extensions of these studies in vivo revealed
      prominent hypoxia-elicited increases in intestinal permeability in ITF null mice.
      HIF-1-dependent induction of ITF may provide an adaptive link for maintenance of
      barrier function during hypoxia.

PMID- 11342588
TI  - The adenylate cyclase toxin of Bordetella pertussis binds to target cells via the
      alpha(M)beta(2) integrin (CD11b/CD18).
AB  - The adenylate cyclase toxin (CyaA) of Bordetella pertussis is a major virulence
      factor required for the early phases of lung colonization. It can invade
      eukaryotic cells where, upon activation by endogenous calmodulin, it catalyzes
      the formation of unregulated cAMP levels. CyaA intoxication leads to evident
      toxic effects on macrophages and neutrophils. Here, we demonstrate that CyaA uses
      the alpha(M)beta(2) integrin (CD11b/CD18) as a cell receptor. Indeed, the
      saturable binding of CyaA to the surface of various hematopoietic cell lines
      correlated with the presence of the alpha(M)beta(2) integrin on these cells.
      Moreover, binding of CyaA to various murine cell lines and human neutrophils was
      specifically blocked by anti-CD11b monoclonal antibodies. The increase of
      intracellular cAMP level and cell death triggered by CyaA intoxication was also
      specifically blocked by anti-CD11b monoclonal antibodies. In addition, CyaA bound
      efficiently and triggered intracellular cAMP increase and cell death in Chinese
      hamster ovary cells transfected with alpha(M)beta(2) (CD11b/CD18) but not in
      cells transfected with the vector alone or with the alpha(X)beta(2) (CD11c/CD18)
      integrin. Thus, the cellular distribution of CD11b, mostly on neutrophils,
      macrophages, and dendritic and natural killer cells, supports a role for CyaA in
      disrupting the early, innate antibacterial immune response.

PMID- 11342589
TI  - An endoplasmic reticulum retention function for the cytoplasmic tail of the human
      pre-T cell receptor (TCR) alpha chain: potential role in the regulation of cell
      surface pre-TCR expression levels.
AB  - The pre-T cell receptor (TCR), which consists of a TCR-beta chain paired with pre
      TCR-alpha (pTalpha) and associated with CD3/zeta components, is a critical
      regulator of T cell development. For unknown reasons, extremely low pre-TCR
      levels reach the plasma membrane of pre-T cells. By transfecting chimeric TCR
      alpha-pTalpha proteins into pre-T and mature T cell lines, we show here that the
      low surface expression of the human pre-TCR is pTalpha chain dependent.
      Particularly, the cytoplasmic domain of pTalpha is sufficient to reduce surface
      expression of a conventional TCR-alpha/beta to pre-TCR expression levels. Such
      reduced expression cannot be attributed to qualitative differences in the
      biochemical composition of the CD3/zeta modules associated with pre-TCR and TCR
      surface complexes. Rather, evidence is provided that the pTalpha cytoplasmic tail
      also causes a reduced surface expression of individual membrane molecules such as
      CD25 and CD4, which are shown to be retained in the endoplasmic reticulum (ER).
      Native pTalpha is also observed to be predominantly ER localized. Finally,
      sequential truncations along the pTalpha cytoplasmic domain revealed that removal
      of the COOH-terminal 48 residues is sufficient to release a CD4-pTalpha chimera
      from ER retention, and to restore native CD4 surface expression levels. As such a
      truncation in pTalpha also correlates with enhanced pre-TCR expression, the
      observed pTalpha ER retention function may contribute to the regulation of
      surface pre-TCR expression on pre-T cells.

PMID- 11342590
TI  - Sulfated tyrosines contribute to the formation of the C5a docking site of the
      human C5a anaphylatoxin receptor.
AB  - The complement anaphylatoxin C5a and its seven-transmembrane segment (7TMS)
      receptor play an important role in host defense and in a number of inflammation
      associated pathologies. The NH(2)-terminal domain of the C5a receptor (C5aR/CD88)
      contributes substantially to its ability to bind C5a. Here we show that the
      tyrosines at positions 11 and 14 of the C5aR are posttranslationally modified by
      the addition of sulfate groups. The sulfate moieties of each of these tyrosines
      are critical to the ability of the C5aR to bind C5a and to mobilize calcium. A
      C5aR variant lacking these sulfate moieties efficiently mobilized calcium in
      response to a small peptide agonist, but not to C5a, consistent with a two-site
      model of ligand association in which the tyrosine-sulfated region of the C5aR
      mediates the initial docking interaction. A peptide based on the NH(2) terminus
      of the C5aR and sulfated at these two tyrosines, but not its unsulfated analogue
      or a doubly sulfated control peptide, partially inhibited C5a association with
      its receptor. These observations clarify structural and mutagenic studies of the
      C5a/C5aR association and suggest that related 7TMS receptors are also modified by
      functionally important sulfate groups on their NH(2)-terminal tyrosines.

PMID- 11342591
TI  - Staphylococcus aureus resistance to human defensins and evasion of neutrophil
      killing via the novel virulence factor MprF is based on modification of membrane
      lipids with l-lysine.
AB  - Defensins, antimicrobial peptides of the innate immune system, protect human
      mucosal epithelia and skin against microbial infections and are produced in large
      amounts by neutrophils. The bacterial pathogen Staphylococcus aureus is
      insensitive to defensins by virtue of an unknown resistance mechanism. We
      describe a novel staphylococcal gene, mprF, which determines resistance to
      several host defense peptides such as defensins and protegrins. An mprF mutant
      strain was killed considerably faster by human neutrophils and exhibited
      attenuated virulence in mice, indicating a key role for defensin resistance in
      the pathogenicity of S. aureus. Analysis of membrane lipids demonstrated that the
      mprF mutant no longer modifies phosphatidylglycerol with l-lysine. As this
      unusual modification leads to a reduced negative charge of the membrane surface,
      MprF-mediated peptide resistance is most likely based on repulsion of the
      cationic peptides. Accordingly, inactivation of mprF led to increased binding of
      antimicrobial peptides by the bacteria. MprF has no similarity with genes of
      known function, but related genes were identified in the genomes of several
      pathogens including Mycobacterium tuberculosis, Pseudomonas aeruginosa, and
      Enterococcus faecalis. MprF thus constitutes a novel virulence factor, which may
      be of general relevance for bacterial pathogens and represents a new target for
      attacking multidrug resistant bacteria.

PMID- 11342592
TI  - Invasion and persistent intracellular colonization of erythrocytes. A unique
      parasitic strategy of the emerging pathogen Bartonella.
AB  - The expanding genus Bartonella includes zoonotic and human-specific pathogens
      that can cause a wide range of clinical manifestations. A productive infection
      allowing bacterial transmission by blood-sucking arthropods is marked by an
      intraerythrocytic bacteremia that occurs exclusively in specific human or animal
      reservoir hosts. Incidental human infection by animal-adapted bartonellae can
      cause disease without evidence for erythrocyte parasitism. A better understanding
      of the intraerythrocytic lifestyle of bartonellae may permit the design of
      strategies to control the reservoir and transmittable stages of these emerging
      pathogens. We have dissected the process of Bartonella erythrocyte parasitism in
      experimentally infected animals using a novel approach for tracking blood
      infections based on flow cytometric quantification of green fluorescent protein
      expressing bacteria during their interaction with in vivo-biotinylated
      erythrocytes. Bacteremia onset occurs several days after inoculation by a
      synchronous wave of bacterial invasion into mature erythrocytes. Intracellular
      bacteria replicate until reaching a stagnant number, which is sustained for the
      remaining life span of the infected erythrocyte. The initial wave of erythrocyte
      infection is followed by reinfection waves occurring at intervals of several
      days. Our findings unravel a unique bacterial persistence strategy adapted to a
      nonhemolytic intracellular colonization of erythrocytes that preserves the
      pathogen for efficient transmission by blood-sucking arthropods.

PMID- 11342593
TI  - Signal transducer and activator of transcription 6 controls chemokine production
      and T helper cell type 2 cell trafficking in allergic pulmonary inflammation.
AB  - Antigen-specific CD4 T helper type 2 (Th2) cells play a pivotal role in the
      induction of allergic asthma, but the mechanisms regulating their recruitment
      into the airways are unknown. Signal transducer and activator of transcription
      factor (Stat)6 is a transcription factor essential for Th2 cell differentiation.
      Here we show that Stat6 also controls Th2 cell recruitment and effector function
      in allergic inflammation in vivo. To isolate the role of Stat6 in regulating Th2
      cell trafficking and effector function from its role in Th2 cell differentiation,
      we used a murine model of asthma in which in vitro-differentiated Stat6(+/+)
      antigen-specific Th2 cells were adoptively transferred into naive Stat6(-/-) and
      Stat6(+/+) mice followed by aerosol antigen challenge. We found that all of the
      features of asthma, including Th2 cell accumulation, Th2 and eosinophil-active
      chemokine production, and airway eosinophilia, mucus production, and
      hyperresponsiveness seen in Stat6(+/+) mice, were dramatically absent in Stat6(
      /)- mice that received Stat6(+/)+ antigen-specific Th2 cells. Our findings
      establish Stat6 as essential for Th2 cell trafficking and effector function and
      suggest that interruption of Stat6 signaling in resident cells of the lung is a
      novel approach to asthma therapy.

PMID- 11342594
TI  - The Exocytosis-regulatory protein synaptotagmin VII mediates cell invasion by
      Trypanosoma cruzi.
AB  - The intracellular protozoan parasite Trypanosoma cruzi causes Chagas' disease,
      which affects millions of people in Latin America. T. cruzi enters a large number
      of cell types by an unusual mechanism that involves Ca(2+)-triggered fusion of
      lysosomes with the plasma membrane. Here we show that synaptotagmin VII (Syt
      VII), a ubiquitously expressed synaptotagmin isoform that regulates exocytosis of
      lysosomes, is localized on the membranes of intracellular vacuoles containing T.
      cruzi. Antibodies against the C(2)A domain of Syt VII or recombinant peptides
      including this domain inhibit cell entry by T. cruzi, but not by Toxoplasma
      gondii or Salmonella typhimurium. The C(2)A domains of other ubiquitously
      expressed synaptotagmin isoforms have no effect on T. cruzi invasion, and
      mutation of critical residues on Syt VII C(2)A abolish its inhibitory activity.
      These findings indicate that T. cruzi exploits the Syt VII-dependent, Ca(2+)
      regulated lysosomal exocytic pathway for invading host cells.

PMID- 11342595
TI  - The CCR7 ligand elc (CCL19) is transcytosed in high endothelial venules and
      mediates T cell recruitment.
AB  - Lymphocyte homing to secondary lymphoid tissue is defined by a multistep sequence
      of interactions between lymphocytes and endothelial cells in high endothelial
      venules (HEVs). After initial selectin-mediated tethering and rolling, firm
      adhesion of lymphocytes requires rapid upregulation of lymphocyte integrin
      adhesiveness. This step is mediated in part by the HEV-derived chemokine SLC
      (secondary lymphoid-tissue chemokine, or CCL21) that binds to the CC chemokine
      receptor (CCR)7 on lymphocytes. However, the CC chemokine ELC (Epstein-Barr virus
      induced molecule 1 ligand chemokine, or CCL19) shares the same receptor, and ELC
      transcripts have been observed in the T cell areas of lymphoid organs. Here, we
      show that perivascular ELC is transcytosed to the luminal surfaces of HEVs and
      enables efficient T cell homing to lymph nodes. In situ hybridization on sections
      of human tonsil showed no ELC mRNA in HEVs, but immunostaining revealed ELC
      protein in cytoplasmic vesicles of HEV cells. Furthermore, ELC injected into the
      footpads of mice entered the draining lymph nodes and was presented by HEVs.
      Finally, intracutaneous injections of ELC in mice lacking functionally relevant
      ELC and SLC (plt/plt mice) restored T cell trafficking to draining lymph nodes as
      efficiently as SLC. We conclude that perivascular ELC is transcytosed to the
      luminal surfaces of HEVs and participates in CCR7-mediated triggering of
      lymphocyte arrest.

PMID- 11342596
TI  - Fatal attraction evaded. How pathogenic bacteria resist cationic polypeptides.

PMID- 11342597
TI  - Cutting edge: FISP (IL-4-induced secreted protein), a novel cytokine-like
      molecule secreted by Th2 cells.
AB  - Th cell subsets, namely Th1 and Th2 cells, play an important role in mounting an
      immune response against invading pathogens. Several genes are selectively up
      regulated during differentiation and effector phases of Th subsets. In this
      study, we report the identification of a novel cytokine-like molecule designated
      FISP (IL-4-induced secreted protein), which is selectively expressed and secreted
      by Th2 cells. Detectable levels of FISP are observed only 3 days after initiation
      of Th2 differentiation. Expression of FISP in developing Th cells requires at
      least two signals: TCR signaling involving protein kinase C activation and STAT6
      dependent IL-4R signaling.

PMID- 11342598
TI  - Cutting edge: antigen-independent CD8 T cell proliferation.
AB  - Recent analyses of CD8 T cell responses to Listeria monocytogenes infection
      demonstrate that the duration of in vivo T cell proliferation is not determined
      by the amount or duration of Ag presentation. However, the extent to which T
      lymphocytes are capable of proliferating in the absence of Ag is unknown. Herein
      we demonstrate that CD8 T lymphocytes undergo up to eight rounds of proliferation
      in the absence of Ag following transient, 2.5-h in vitro antigenic stimulation.
      Ag-independent expansion of CD8 T cells is driven by IL-2 and is further
      augmented by IL-7 or IL-15. These experiments clearly demonstrate that CD8 T
      cells undergo prolonged proliferation following transient Ag exposure and support
      the notion that in vivo CD8 T cell expansion following infection can be uncoupled
      from Ag presentation.

PMID- 11342599
TI  - Cutting edge: a NK complex-linked locus governs acute versus latent herpes
      simplex virus infection of neurons.
AB  - Herpes simplex causes latent infections that periodically reactivate. Specific
      immunization attempts are failing to control herpes, prompting a fresh look at
      which host responses predominate. We report a NK complex-linked genetic locus,
      Rhs1, whose alleles influence the magnitude of experimental herpes simplex. Rhs1
      provided rapid control of primary infection but caused a reciprocal increase in
      the number of latently infected neurons. Thus, in principle, establishment of
      latency is a consequence of efficient front line defense against herpesvirus
      infection. Based on conservation between human and mouse NK complexes, the data
      predict the presence of a human Rhs1 orthologue on chromosome 12p12-13.

PMID- 11342600
TI  - Cutting edge: a single MHC anchor residue alters the conformation of a peptide
      MHC complex inducing T cells that survive negative selection.
AB  - We generated transgenic mice that expressed hen egg-white lysozyme (HEL) under a
      class II MHC promoter. The A7 line expressed HEL with a point mutation in the
      Asp(52) residue, the main anchor amino acid responsible for the selection of the
      chemically dominant family of peptides (52-60) by I-A(k) molecules. Mice
      expressing HEL with Ala(52) were completely unresponsive when immunized with the
      same protein, i.e., HEL A52. However, the same mice immunized with wild-type HEL
      elicited T cells that recognized a conformation of the 52-61 core sequence
      uniquely different between Asp(52) and Ala(52) containing peptides. Importantly,
      some T cells also recognized the HEL A52 peptide given exogenously but not the
      same peptide processed from HEL A52 protein. Thus, a core MHC anchor residue
      influences markedly the specificity of the T cells. We discuss the relevance of
      these findings to autoimmunity and vaccination with altered peptides.

PMID- 11342601
TI  - Cutting edge: systemic inhibition of angiogenesis underlies resistance to tumors
      during acute toxoplasmosis.
AB  - The ability of various infections to suppress neoplastic growth has been well
      documented. This phenomenon has been traditionally attributed to infection
      induced concomitant, cell-mediated antitumor immunity. We found that infection
      with Toxoplasma gondii effectively blocked neoplastic growth of a nonimmunogenic
      B16.F10 melanoma. Moreover, this effect was independent of cytotoxic T or NK
      cells, production of NO by macrophages, or the function of the cytokines IL-12
      and TNF-alpha. These findings suggested that antitumor cytotoxicity was not the
      primary mechanism of resistance. However, infection was accompanied by strong,
      systemic suppression of angiogenesis, both in a model system and inside the
      nascent tumor. This suppression resulted in severe hypoxia and avascular necrosis
      that are incompatible with progressive neoplastic growth. Our results identify
      the suppression of tumor neovascularization as a novel mechanism critical for
      infection-induced resistance to tumors.

PMID- 11342602
TI  - Mycobacterium leprae-specific, HLA class II-restricted killing of human Schwann
      cells by CD4+ Th1 cells: a novel immunopathogenic mechanism of nerve damage in
      leprosy.
AB  - Peripheral nerve damage is a major complication of reversal (or type-1) reactions
      in leprosy. The pathogenesis of nerve damage remains largely unresolved, but
      detailed in situ analyses suggest that type-1 T cells play an important role.
      Mycobacterium leprae is known to have a remarkable tropism for Schwann cells of
      the peripheral nerve. Reversal reactions in leprosy are often accompanied by
      severe and irreversible nerve destruction and are associated with increased
      cellular immune reactivity against M. leprae. Thus, a likely immunopathogenic
      mechanism of Schwann cell and nerve damage in leprosy is that infected Schwann
      cells process and present Ags of M. leprae to Ag-specific, inflammatory type-1 T
      cells and that these T cells subsequently damage and lyse infected Schwann cells.
      Thus far it has been difficult to study this directly because of the inability to
      grow large numbers of human Schwann cells. We now have established long-term
      human Schwann cell cultures from sural nerves and show that human Schwann cells
      express MHC class I and II, ICAM-1, and CD80 surface molecules involved in Ag
      presentation. Human Schwann cells process and present M. leprae, as well as
      recombinant proteins and peptides to MHC class II-restricted CD4(+) T cells, and
      are efficiently killed by these activated T cells. These findings elucidate a
      novel mechanism that is likely involved in the immunopathogenesis of nerve damage
      in leprosy.

PMID- 11342603
TI  - CD44-deficient mice exhibit enhanced hepatitis after concanavalin A injection:
      evidence for involvement of CD44 in activation-induced cell death.
AB  - Administration of Con A induces severe injury to hepatocytes in mice and is
      considered to be a model for human hepatitis. In the current study, we
      investigated the role of CD44 in Con A-induced hepatitis. Intravenous
      administration of Con A (20 mg/kg) caused 100% mortality in C57BL/6 CD44-knockout
      (KO) mice, although it was not lethal in C57BL/6 CD44 wild-type (WT) mice.
      Administration of lower doses of Con A (12 mg/kg body weight) into CD44 WT mice
      induced hepatitis as evident from increased plasma aspartate aminotransferase
      levels accompanied by active infiltration of mononuclear cells and neutrophils,
      and significant induction of apoptosis in the liver. Interestingly, CD44 KO mice
      injected with similar doses of Con A exhibited more severe acute suppurative
      hepatitis. Transfer of spleen cells from Con A-injected CD44 KO mice into CD44 WT
      mice induced higher levels of hepatitis when compared with transfer of similar
      cells from CD44 WT mice into CD44 WT mice. The increased hepatitis seen in CD44
      KO mice was accompanied by increased production of cytokines such as TNF-alpha,
      IL-2 and IFN-gamma, but not Fas or Fas ligand. The increased susceptibility of
      CD44 KO mice to hepatitis correlated with the observation that T cells from CD44
      KO mice were more resistant to activation-induced cell death when compared with
      the CD44 WT mice. Together, these data demonstrate that activated T cells use
      CD44 to undergo apoptosis, and dysregulation in this pathway could lead to
      increased pathogenesis in a number of diseases, including hepatitis.

PMID- 11342604
TI  - Distinct mechanisms contribute to generate and change the CD4:CD8 cell ratio
      during thymus development: a role for the Notch ligand, Jagged1.
AB  - In adult life, the high CD4:CD8 cell ratio observed in peripheral lymphoid organs
      originates in the thymus. Our results show that the low peripheral CD4:CD8 cell
      ratio seen during fetal life also has an intrathymic origin. This distinct
      production of CD4(+)CD8(-) and CD4(-)CD8(+) thymocytes is regulated by the
      developmental age of the thymic stroma. The differential expression of Notch
      receptors and their ligands, especially Jagged1, throughout thymus development
      plays a key role in the generation of the different CD4:CD8 cell ratios. We also
      show that the intrathymic CD4:CD8 cell ratio sharply changes from fetal to adult
      values around birth. Differences in the proliferation and emigration rates of the
      mature thymocyte subsets contribute to this change.

PMID- 11342605
TI  - Requirement for leptin in the induction and progression of autoimmune
      encephalomyelitis.
AB  - Recent evidence indicates that leptin modifies T cell immunity, and may provide a
      key link between nutritional deficiency and immune dysfunction. To study the
      influence of leptin on autoimmunity, susceptibility to experimental autoimmune
      encephalomyelitis induced by immunization with a myelin-derived peptide was
      examined in leptin-deficient, C57BL/6J-ob/ob mice, with or without leptin
      replacement, and in wild-type controls. Leptin replacement converted disease
      resistance to susceptibility in the C57BL/6J-ob/ob mice; this was accompanied by
      a switch from a Th2 to Th1 pattern of cytokine release and consequent reversal of
      Ig subclass production. Our findings suggest that leptin is required for the
      induction and maintenance of an effective proinflammatory immune response in the
      CNS.

PMID- 11342606
TI  - Human dendritic cells are activated by chimeric human papillomavirus type-16
      virus-like particles and induce epitope-specific human T cell responses in vitro.
AB  - Human papillomavirus (HPV)-derived chimeric virus-like particles (VLPs) are the
      leading candidate vaccine for the treatment or prevention of cervical cancer in
      humans. Dendritic cells (DCs) are the most potent inducers of immune responses
      and here we show for the first time evidence for binding of chimeric HPV-16 VLPs
      to human peripheral blood-derived DCS: Incubation of immature human DCs with VLPs
      for 48 h induced a significant up-regulation of the CD80 and CD83 molecules as
      well as secretion of IL-12. Confocal microscopy analysis revealed that cell
      surface-bound chimeric VLPs were taken up by DCS: Moreover, DCs loaded with
      chimeric HPV-16 L1L2-E7 VLPs induced an HLA-*0201-restricted human T cell
      response in vitro specific for E7-derived peptides. These results clearly
      demonstrate that immature human DCs are fully activated by chimeric HPV-16 VLPs
      and subsequently are capable of inducing endogenously processed epitope-specific
      human T cell responses in vitro. Overall, these findings could explain the high
      immunogenicity and efficiency of VLPs as vaccines.

PMID- 11342607
TI  - Distinct BMI-1 and EZH2 expression patterns in thymocytes and mature T cells
      suggest a role for Polycomb genes in human T cell differentiation.
AB  - BMI-1 and EZH2 Polycomb-group (PcG) proteins belong to two distinct protein
      complexes involved in the regulation of hematopoiesis. Using unique PcG-specific
      antisera and triple immunofluorescence, we found that mature resting peripheral T
      cells expressed BMI-1, whereas dividing blasts were EZH2(+). By contrast,
      subcapsular immature double-negative (DN) (CD4(-)/CD8(-)) T cells in the thymus
      coexpressed BMI-1 and EZH2 or were BMI-1 single positive. Their descendants,
      double-positive (DP; CD4(+)/CD8(+)) cortical thymocytes, expressed EZH2 without
      BMI-1. Most EZH2(+) DN and DP thymocytes were dividing, while DN BMI-1(+)/EZH2(-)
      thymocytes were resting and proliferation was occasionally noted in DN BMI
      1(+)/EZH2(+) cells. Maturation of DP cortical thymocytes to single-positive
      (CD4(+)/CD8(-) or CD8(+)/CD4(-)) medullar thymocytes correlated with decreased
      detectability of EZH2 and continued relative absence of BMI-1. Our data show that
      BMI-1 and EZH2 expression in mature peripheral T cells is mutually exclusive and
      linked to proliferation status, and that this pattern is not yet established in
      thymocytes of the cortex and medulla. T cell stage-specific PcG expression
      profiles suggest that PcG genes contribute to regulation of T cell
      differentiation. They probably reflect stabilization of cell type-specific gene
      expression and irreversibility of lineage choice. The difference in PcG
      expression between medullar thymocytes and mature interfollicular T cells
      indicates that additional maturation processes occur after thymocyte
      transportation from the thymus.

PMID- 11342608
TI  - Definition of a novel cellular constituent of the bone marrow that regulates the
      response of immature B cells to B cell antigen receptor engagement.
AB  - Previously we defined a Thy1(dull) bone marrow-derived cell population that
      regulated fate decisions by immature B cells after Ag receptor signaling. The
      microenvironmental signals provided by this cell population were shown to
      redirect the B cell Ag receptor -induced apoptotic response of immature B cells
      toward continued recombination-activating gene (RAG) expression and secondary
      light chain recombination (receptor editing). Neither the identity of the cell
      responsible for this activity nor its role in immature B cell development in vivo
      were addressed by these previous studies. Here we show that this protective
      microenvironmental niche is defined by the presence of a novel Thy1(dull),
      DX5(pos) cell that can be found in close association with immature B cells in
      vivo. Depletion of this cell eliminates the anti-apoptotic effect of bone marrow
      in vitro and leads to a significant decrease in the number and frequency of bone
      marrow immature B cells in vivo. We propose that, just as the bone marrow
      environment is essential for the survival and progression of pro-B and pre-B
      cells through their respective developmental checkpoints, this cellular niche
      regulates the progression of immature stage B cells through negative selection.

PMID- 11342609
TI  - A requirement for IL-2/IL-2 receptor signaling in intrathymic negative selection.
AB  - The nature of the signals that influence thymocyte selection and determine the
      fate of CD4(+)8(+) (double positive) thymocytes remains unclear. Cytokines
      produced locally in the thymus may modulate signals delivered by TCR-MHC/peptide
      interactions and thereby influence the fate of double-positive thymocytes.
      Because the IL-2/IL-2R signaling pathway has been implicated in thymocyte and
      peripheral T cell survival, we investigated the possibility that IL-2/IL-2R
      interactions contribute to the deletion of self-reactive, Ag-specific thymocytes.
      By using nontransgenic and transgenic IL-2-sufficient and -deficient animal model
      systems, we have shown that during TCR-mediated thymocyte apoptosis, IL-2 protein
      is expressed in situ in the thymus, and apoptotic thymocytes up-regulate
      expression of IL-2RS: IL-2R(+) double-positive and CD4 single-positive thymocytes
      undergoing activation-induced cell death bind and internalize IL-2. IL-2
      deficient thymocytes are resistant to TCR/CD3-mediated apoptotic death, which is
      overcome by providing exogenous IL-2 to IL-2(-/-) mice. Furthermore, disruption
      or blockade of IL-2/IL-2R interactions in vivo during Ag-mediated selection
      rescues some MHC class II-restricted thymocytes from apoptosis. Collectively,
      these findings provide evidence for the direct involvement of the IL-2/IL-2R
      signaling pathway in the deletion of Ag-specific thymocyte populations and
      suggest that CD4 T cell hyperplasia and autoimmunity in IL-2(-/-) mice is a
      consequence of ineffective deletion of self-reactive T cells.

PMID- 11342610
TI  - Protein kinase C-theta mediates a selective T cell survival signal via
      phosphorylation of BAD.
AB  - Protein kinase C (PKC)-activating phorbol esters protect T cells from Fas-induced
      apoptosis. However, the mechanism of this protective effect and the identity of
      the relevant PKC isoform(s) are poorly understood. Here, we show that PKCtheta
      plays a selective and important role in this protection. Fas triggering led to a
      selective caspase-3-dependent cleavage of the enzyme and proteasome-mediated
      degradation and inactivation of its catalytic fragment. These events preceded the
      onset of apoptosis. Pharmacological inhibition of PKCtheta promoted Fas-mediated
      apoptosis in three different types of T cells. Conversely, constitutively active
      PKCtheta (and, to a lesser degree, PKCepsilon) selectively protected T cells from
      Fas-induced apoptosis. We provide evidence that the distant Bcl-2 family member,
      BAD, is a PKCtheta substrate, is phosphorylated by TCR stimulation, and can
      mediate at least in part the anti-apoptotic effect of PKCtheta.

PMID- 11342611
TI  - Generation of macrophages from early T progenitors in vitro.
AB  - Early T progenitors in the thymus have been reported to have the capacity to
      develop into B cells, thymic dendritic cells, and NK cells. Here we describe
      conditions that induce early T progenitors to develop into macrophages.
      Initially, we observed that early T progenitors could be induced to develop into
      macrophages by cytokines produced from a thymic stromal cell line, TFGD, and
      later we found that the cytokine mixture of M-CSF plus IL-6 plus IL-7 also
      induced macrophage differentiation from pro-T cells. M-CSF by itself was unable
      to induce macrophage differentiation from early T progenitors. To correlate this
      observation with the developmental potential of early T progenitors, mouse
      embryonic thymocytes were sorted into four populations, pro-T1 to pro-T4, based
      on the expression of CD44 and CD25, and then cultured with TFGD culture
      supernatant. We found that pro-T1 and pro-T2 cells, but not pro-T3 and pro-T4
      cells, generate macrophages. Limiting dilution analysis of the differentiation
      capability of sorted pro-T2 cells also confirmed that pro-T2 cells could generate
      macrophages. These results suggest that T cells and thymic macrophages could
      originate from a common intrathymic precursor.

PMID- 11342612
TI  - Murine IL-10 gene transfer inhibits established collagen-induced arthritis and
      reduces adenovirus-mediated inflammatory responses in mouse liver.
AB  - The effects of homologous IL-10 administration during an established autoimmune
      disease are controversial, given its reported immunostimulatory and
      immunosuppressive properties. Studies of collagen-induced arthritis have shown
      efficacy with repeated administrations of IL-10; however, when the EBV IL-10
      homologue was administered via adenovirus gene transfer technology the results
      were equivocal. Therefore, the present study was undertaken to elucidate the
      effects of prolonged homologous IL-10 administration via adenovirus-mediated gene
      delivery on the progression of established arthritis. Collagen type II (CII)
      immunized mice received i.v. injections of 10(7) or 10(8) PFU of an E1-deleted
      adenoviral vector containing the murine IL-10 gene (AdIL-10), after arthritis
      onset. Mice were monitored for 3 wk for disease progression, and gene
      transduction was assessed by quantification of serum mIL-10. CII-specific cell
      mediated and humoral immune responses were analyzed by lymph node cell
      proliferation, cytokine production, and anti-CII Ab responses. Furthermore,
      because adenoviral vectors have been reported to induce organ dysfunction due to
      cell-mediated immune responses to the viral Ags, we have also evaluated delayed
      type hypersensitivity responses and reactive hepatitis to the systemically
      delivered adenovirus and whether the IL-10 produced could influence those
      responses. Sustained suppression of autoimmune arthritis and elevated serum
      levels of IL-10 were achieved in our study. AdIL-10 treatment reduced cell
      mediated immune reactivity, but did not affect humoral responses. Furthermore, IL
      10 was able to reduce, but not totally abrogate, adenovirus-induced hepatic
      inflammation. These findings provide further insights into the diverse interplay
      of immune processes involved in autoimmune inflammation and the mechanism of
      cytokine immunotherapy.

PMID- 11342613
TI  - Inhibition of antigen-induced mediator release from IgE-sensitized cells by a
      monoclonal anti-Fc epsilon RI alpha-chain receptor antibody: implications for the
      involvement of the membrane-proximal alpha-chain region in Fc epsilon RI-mediated
      cell activation.
AB  - The interaction between human IgE and its high affinity receptor, FcepsilonRI, is
      a critical event in mediating the allergic response. Aggregation of the alpha
      chain of FcepsilonRI (FcepsilonRIalpha) occurs via cross-linking of receptor
      bound IgE by Ag, resulting in cell activation and the release of mediators of
      hypersensitivity. Recently, we mapped the epitopes of two anti-FcepsilonRIalpha
      mAbs, 15/1 and 5H5F8. In contrast to 15/1, mAb 5H5F8 does not inhibit IgE binding
      to FcepsilonRIalpha. Here we demonstrate both 5H5F8 binding to FcepsilonRI(+)
      cells as well as a high level of IgE binding to 5H5F8-saturated cells. At the
      same time 5H5F8 strongly inhibits hexosaminidase release and Ca(2+) flux after Ag
      triggering from human IgE-sensitized RBL-2H3 cells stably transfected with human
      FcepsilonRIalpha. Further, 5H5F8 and its Fab inhibit sulfidoleukotriene and
      histamine release from primary human peripheral blood leukocytes, including cells
      bearing endogenous IGE: Furthermore, we confirm that 5H5F8 maps to a linear
      peptide sequence in close proximity to the cell membrane. Two chemically
      synthesized peptides containing the 5H5F8 epitope sequence PREKY were selected
      for detailed analysis of 5H5F8 and 5H5F8 Fab binding and were found to produce
      K(d) values of similar magnitude to that observed for binding to recombinant
      FcepsilonRIalpha. These peptides may prove useful as targets for the
      identification of antagonists of FcepsilonRIalpha-mediated biological activity.
      Moreover, our data indicate that FcepsilonRIalpha-mediated activation may involve
      a novel alpha-chain epitope in an early step of the cell-triggering pathway
      leading to cellular activation.

PMID- 11342614
TI  - Early intestinal Th1 inflammation and mucosal T cell recruitment during acute
      graft-versus-host reaction.
AB  - Little is understood about the earliest cytokine responses and the role(s) of
      donor CD4 T cells in the intestine during the induced graft-vs-host reaction
      (GVHR). We investigated the activation and mucosal homing phenotype of the donor
      CD4 cells and the kinetics of cytokine responses within the intestine and
      associated lymphoid tissues during early GVHR. Significant frequencies of donor
      CD4 cells accumulated within recipient Peyer's patches (PP), mesenteric lymph
      nodes (MLN), lamina propria (LP), and spleen (SP), during the first 9 days of
      GVHR. Many donor CD4 cells in SP, MLN, and LP expressed CD44 and also expressed
      de novo the mucosal homing integrin alpha(4)beta(7) (LPAM-1). A large IFN-gamma
      response occurred by day 3 in cells from PP and MLN, but much later (day 9) in SP
      and LP cells. IL-10 production by SP and MLN cells was elevated initially but
      declined substantially by day 9. IL-4 production by SP, MLN, and PP cells was low
      on day 3 and showed gradual decline in LP by day 9. IL-5 production by LP cells
      gradually increased in direct contrast to IL-5 production by MLN cells. The MLN
      CD4 cells showed the most dynamic changes, with high numbers of
      activated/effector donor CD4 cells and altered cytokine production consistent
      with a developing Th1 response. The IFN-gamma responses in PP and MLN preceded
      that of the SP, suggesting an intestinal origin for some Th1 effector cells in
      GVHR. Donor CD4 T cells apparently acquire the ability to home to the LP during
      early GVHR.

PMID- 11342615
TI  - Histamine induces CD86 expression and chemokine production by human immature
      dendritic cells.
AB  - Mast cells and immature dendritic cells (DC) are in close contact in peripheral
      tissues. Upon activation, mast cells release histamine, a mediator involved in
      the immediate hypersensitivity reaction. We therefore tested whether histamine
      could affect human DC activation and maturation. Histamine induces CD86
      expression on immature DC in a dose-dependent (significant at 10(-7) M) and
      transient manner (maximal after 24-h stimulation). Histamine also transiently up
      regulates the expression of the costimulatory and accessory molecules, CD40,
      CD49d, CD54, CD80, and MHC class II. As a consequence, immature DC exposed for 24
      h to histamine stimulate memory T cells more efficiently than untreated DC. In
      addition, histamine induces a potent production of IL-6, IL-8, monocyte
      chemoattractant protein 1, and macrophage-inflammatory protein 1alpha by immature
      DC and also up-regulates IL-1beta, RANTES, and macrophage-inflammatory protein
      1beta but not TNF-alpha and IL-12 mRNA expression. Histamine activates immature
      DC through both the H1 and H2 receptors. However, histamine-treated DC do not
      have a phenotype of fully mature cells, as they do neither show significant
      changes in the expression of the chemokine receptors, CCR5, CCR7 and CXC
      chemokine receptor 4, nor expression of CD83 de novo. These data demonstrate that
      histamine activates immature DC and induces chemokine production, thereby
      suggesting that histamine, via stimulation of resident DC, may participate
      locally in T cell stimulation and in the late inflammatory reaction associated
      with allergic disorders.

PMID- 11342616
TI  - An IFN-gamma-dependent pathway controls stimulation of memory phenotype CD8+ T
      cell turnover in vivo by IL-12, IL-18, and IFN-gamma.
AB  - Unlike naive T cells, memory phenotype (CD44(high)) T cells exhibit a high
      background rate of turnover in vivo. Previous studies showed that the turnover of
      memory phenotype CD8(+) (but not CD4(+)) cells in vivo can be considerably
      enhanced by products of infectious agents such as LPS. Such stimulation is TCR
      independent and hinges on the release of type I IFNs (IFN-I) which leads to the
      production of an effector cytokine, probably IL-15. In this study, we describe a
      second pathway of CD44(high) CD8(+) stimulation in vivo. This pathway is IFN
      gamma rather than IFN-I dependent and is mediated by at least three cytokines, IL
      12, IL-18, and IFN-gamma. As for IFN-I, these three cytokines are nonstimulatory
      for purified T cells and under in vivo conditions probably act via production of
      IL-15.

PMID- 11342617
TI  - Differential regulation of Th1 and Th2 functions of NKT cells by CD28 and CD40
      costimulatory pathways.
AB  - Valpha14 NKT cells produce large amounts of IFN-gamma and IL-4 upon recognition
      of their specific ligand alpha-galactosylceramide (alpha-GalCer) by their
      invariant TCR. We show here that NKT cells constitutively express CD28, and that
      blockade of CD28-CD80/CD86 interactions by anti-CD80 and anti-CD86 mAbs inhibits
      the alpha-GalCer-induced IFN-gamma and IL-4 production by splenic Valpha14 NKT
      cells. On the other, the blockade of CD40-CD154 interactions by anti-CD154 mAb
      inhibited alpha-GalCer-induced IFN-gamma production, but not IL-4 production.
      Consistent with these findings, CD28-deficient mice showed impaired IFN-gamma and
      IL-4 production in response to alpha-GalCer stimulation in vitro and in vivo,
      whereas production of IFN-gamma but not IL-4 was impaired in CD40-deficient mice.
      Moreover, alpha-GalCer-induced Th1-type responses, represented by enhanced
      cytotoxic activity of splenic or hepatic mononuclear cells and antimetastatic
      effect, were impaired in both CD28-deficient mice and CD40-deficient mice. In
      contrast, alpha-GalCer-induced Th2-type responses, represented by serum IgE and
      IgG1 elevation, were impaired in the absence of the CD28 costimulatory pathway
      but not in the absence of the CD40 costimulatory pathway. These results indicate
      that CD28-CD80/CD86 and CD40-CD154 costimulatory pathways differentially
      contribute to the regulation of Th1 and Th2 functions of Valpha14 NKT cells in
      vivo.

PMID- 11342618
TI  - Signaling through MHC class II molecules blocks CD95-induced apoptosis.
AB  - B cells are induced to express CD95 upon interaction with T cells. This
      interaction renders the B cells sensitive to CD95-mediated apoptosis, but
      ligation of proviability surface receptors is able to inhibit apoptosis
      induction. MHC class II is a key molecule required for Ag presentation to Th
      cells, productive T cell-B cell interaction, and B cell activation. We
      demonstrate here for the first time that MHC class II ligation also confers a
      rapid resistance to CD95-induced apoptosis, an affect that does not require de
      novo protein synthesis. Signaling through class II molecules blocks the
      activation of caspase 8, but does not affect the association of CD95 and Fas
      associated death domain-containing protein. MHC class II ligation thus blocks
      proximal signaling events in the CD95-mediated apoptotic pathway.

PMID- 11342619
TI  - Involvement of Bik, a proapoptotic member of the Bcl-2 family, in surface IgM
      mediated B cell apoptosis.
AB  - Apoptosis plays a central role in shaping the repertoire of circulating mature B
      lymphocytes, but the underlying molecular mechanisms regulating B cell fate are
      not well understood. Human B104 B lymphoma cells undergo apoptosis after surface
      Ig (sIg)M, but not sIgD, ligation; sIgM-mediated apoptosis of B104 cells
      apparently requires new gene transcription because actinomycin D can inhibit the
      apoptotic response. Here we report that expression of Bik, a proapoptotic member
      of the Bcl-2 family, is greatly increased after sIgM ligation. Bik expression was
      tightly controlled at both transcriptional and post-transcriptional levels.
      Whereas a calcineurin-dependent pathway was essential for Bik mRNA induction,
      both the phosphatidylinositol 3-kinase (PI3K)- and the calcineurin-dependent
      pathways were required for the sustained production of Bik protein. Consistent
      with these findings, sIgD ligation, which leads to the similar calcium
      mobilization and increases in Bik mRNA, induced only a transient activation of
      PI3K and did not lead to sustained Bik protein expression. Furthermore, sustained
      Bik protein expression correlated with B cell apoptosis, as treatment with either
      a calcineurin inhibitor or PI3K inhibitors blocked both sIgM-mediated sustained
      Bik protein induction and apoptosis. In addition, sIgM ligation strongly
      increased the amount of Bik associated with endogenous Bcl-x, but sIgD ligation
      did not. Studies with caspase inhibitors also revealed that Bik and Bcl-x
      interacted upstream of caspases in the B cell apoptosis cascade. Thus, Bik
      protein induction and, subsequently, sequestering of antiapoptotic Bcl-x by Bik
      may play an important role in regulating B cell apoptosis.

PMID- 11342620
TI  - CD45 tyrosine phosphatase controls common gamma-chain cytokine-mediated STAT and
      extracellular signal-related kinase phosphorylation in activated human
      lymphoblasts: inhibition of proliferation without induction of apoptosis.
AB  - The objective of this study was to test whether CD45 signals can influence
      signaling processes in activated human lymphoblasts. To this end, we generated
      lymphoblasts which proliferate in response to common gamma-chain cytokines, but
      readily undergo apoptosis after cytokine withdrawal. In experiments with the
      CD45R0 mAb UCHL-1, but not control CD45 mAbs, we found significant inhibition of
      proliferation. Interestingly, the pan-CD45 mAb GAP8.3, which is most effective in
      inhibition of OKT-3-mediated proliferation in quiescent lymphocytes, was
      ineffective in lymphoblasts. Addition of CD3 mAb OKT-3 had no influence on IL-2
      mediated proliferation (with or without UCHL-1). In contrast, after addition of
      OKT-3 to IL-4- and IL-7-stimulated proliferation assays, UCHL-1 signals could not
      significantly alter cellular proliferation. We did not find induction of
      apoptosis following CD45R0 signaling. In Western blots using mAbs detecting
      phosphorylated STAT-3, STAT-5, STAT-6, or extracellular signal-related kinase
      1/2, we found that CD45R0 signaling could effectively diminish phosphorylation of
      these intracellular signaling components. Using RT-PCR, we found that CD45R0
      signaling inhibited IL-2 mRNA production without major influence on IL-13, IL-5,
      or IFN-gamma mRNA levels. Costimulation with OKT-3 and IL-2 optimally induced
      secretion of IFN-gamma, TNF-alpha, and IL-5, which was not decreased by CD45
      signals. In conclusion, we illustrate that CD45R0 signals control early cytokine
      receptor-associated signaling processes and mRNA and DNA synthesis in activated
      human lymphoblasts. Furthermore, we show the existence of CD45 epitopes (GAP8.3),
      which are active and critical for signaling in quiescent lymphocytes, but are
      nonfunctional in activated human lymphoblasts.

PMID- 11342621
TI  - B cell immunodeficiency fails to develop in CD4-deficient mice infected with BM5:
      murine AIDS as a multistep disease.
AB  - The immunodeficiency syndrome murine AIDS (MAIDS), caused by the BM5 retrovirus
      preparation, involves the activation, division, and subsequent anergy of the
      entire CD4(+) T cell population as well as extensive B cell hyperproliferation
      and hypergammaglobulinemia, resulting in splenomegaly and lymphadenopathy,
      followed many weeks later by death. The development of MAIDS requires CD4(+) T
      cells and MHC class II expression by the infected host, supporting a role for T-B
      interaction in disease development or progression. To explore this possibility,
      we examined development of MAIDS in mice deficient in CD4 (CD4 knockout), in
      which T-B interactions are compromised. We find that in CD4 knockout hosts, BM5
      causes T cell immunodeficiency in the remaining T cells but has only a limited
      ability to induce B cell phenotypic changes, hyperproliferation,
      hypergammaglobulinemia, or splenomegaly. There is also delayed death of infected
      mice. This implies that CD4 dependent T-B interaction is needed to induce the B
      cell aspects of disease and supports a multistep mechanism of disease in which B
      cell changes follow and are caused by CD4(+) T cell effects.

PMID- 11342622
TI  - Requirement for a complex array of costimulators in the negative selection of
      autoreactive thymocytes in vivo.
AB  - Autoreactive thymocytes can be deleted at an immature stage of their development
      by Ag-induced apoptosis or negative selection. In addition to Ag, negative
      selection also requires costimulatory signals from APC. We recently used a fetal
      thymus organ culture system to show that CD5, CD28, and TNF cooperatively
      regulate deletion of autoreactive thymocytes. Although these experiments provided
      strong evidence for the action of several costimulators in negative selection, we
      wished to demonstrate a role for these molecules in a physiologically natural
      model where thymocytes are deleted in vivo by endogenously expressed AGS:
      Accordingly, we examined thymocyte deletion in costimulator-null mice in three
      models of autoantigen-induced negative selection. We compared CD5(-/-) CD28(-/-)
      mice to CD40L(-/-) mice, which exhibited a profound block in negative selection
      in all three systems. Surprisingly, only one of the three models revealed a
      requirement for the CD5 and CD28 costimulators in autoantigen-induced deletion.
      These results suggest that an extraordinarily complex array of costimulators is
      involved in negative selection. We predict that different sets of costimulators
      will be required depending on the timing of negative selection, the Ag, the
      signal strength, the APC, and whether Ag presentation occurs on class I or class
      II MHC molecules.

PMID- 11342623
TI  - Recombinant allergens with reduced allergenicity but retaining immunogenicity of
      the natural allergens: hybrids of yellow jacket and paper wasp venom allergen
      antigen 5s.
AB  - The homologous venom allergen Ag 5s from the yellow jacket (Vespula vulgaris) and
      paper wasp (Polistes annularis) have 59% sequence identity of their respective
      204 and 205 amino acid residues, and they have low degrees of antigenic cross
      reactivity in insect allergic patients and in animal models. Hybrids containing
      different segments of these two vespid Ag 5s were expressed in yeast. Circular
      dichroism spectroscopy suggests the hybrids to have the secondary structure of
      natural Ag 5. Inhibition ELISA with human and murine Abs suggests the hybrids to
      have the discontinuous B cell epitopes of the natural Ag 5 but with an altered
      epitope density. The hybrids were immunogenic in mice for B and T cell responses
      to both Ag 5s. The N-terminal region of Ag 5 was found to contain its dominant B
      cell epitope(s). Hybrids containing 10-49 residues of yellow jacket Ag 5 showed
      100- to 3000-fold reduction in allergenicity when tested by histamine release
      assay with basophils of yellow jacket-sensitive patients. Our findings suggest
      that hybrids represent a useful approach to map the discontinuous B cell epitope
      containing regions of proteins. They also suggest that Ag 5 hybrids may be useful
      immunotherapeutic reagents in man.

PMID- 11342624
TI  - Development of intestinal intraepithelial lymphocytes, NK cells, and NK 1.1+ T
      cells in CD45-deficient mice.
AB  - The transmembrane protein tyrosine phosphatase CD45 is differentially required
      for the development and function of B, T, and NK cells, with mice partially
      deficient for CD45 having a significant inhibition of T cell, but not NK or B
      cell, development. CD45-mediated signaling has also been implicated in the
      development of intrathymic, but not extrathymic, intestinal intraepithelial T
      lymphocytes (iIELs) in the CD45ex6(-/-) mouse. As NK1.1(+) CD3(+) (NK-T) cells
      can also develop through extrathymic pathways, we have investigated the role of
      CD45 in NK-T cell development. In mice with a complete absence of CD45 expression
      (CD45ex9(-/-)) the NK-T cell population was maintained in the iIEL compartment,
      but not in the spleen. Functionally, CD45-deficient NK-T cells were unable to
      secrete IL-4 in response to TCR-mediated signals, a phenotype similar to that of
      CD45-deficient iIELs, in which in vitro cytokine production was dramatically
      reduced. Using the CD45ex9(-/-) mouse strain, we have also demonstrated that only
      one distinct population of NK-T cells (CD8(+)) appears to develop normally in the
      absence of CD45. Interestingly, although an increase in cytotoxic NK cells is
      seen in the absence of CD45, these NK calls are functionally unable to secrete
      IFN-gamma. In the absence of CD45, a significant population of extrathymically
      derived CD8alphaalpha(+) iIELs is also maintained. These results demonstrate that
      in contrast to conventional T cells, CD45 is not required during the development
      of CD8(+) NK-T cells, NK cells, or CD8alphaalpha(+) iIELs, but is essential for
      TCR-mediated function and cytokine production.

PMID- 11342625
TI  - CD8+ tumor-infiltrating lymphocytes are primed for Fas-mediated activation
      induced cell death but are not apoptotic in situ.
AB  - Induction of Fas-mediated activation-induced cell death in antitumor T cells has
      been hypothesized to permit tumor escape from immune destruction. Several
      laboratories have proposed that expression of Fas ligand (L) by tumor is the
      basis for this form of T cell tolerance. In this study, we characterized murine
      tumor-infiltrating lymphocytes (TIL) for activation status, cell cycle status,
      level of apoptosis, cytokine secretion, and proliferative capacity. TILs express
      multiple activation markers (circa CD69, CD95L, CD122, and LFA-1) and contain IL
      2 and IFN-gamma mRNAs, but are neither cycling nor apoptotic in situ. In
      addition, TIL are dramatically suppressed in proliferative response and do not
      secrete IL-2 and IFN-gamma. However, upon purification and activation in vitro,
      TIL secrete high levels of IL-2 and IFN-gamma, enter S phase, and then die by Fas
      mediated apoptosis. Activation by injection of anti-TCR Ab or IL-2 into tumor
      bearing mice induced TIL entrance into S phase preceding apoptosis, showing that
      TIL have functional TCR-mediated signal transduction in situ. Our data
      demonstrate that TIL, not tumor, express both Fas and FasL, are arrested in G(1),
      do not secrete cytokine in situ, and, upon activation in vitro and in vivo,
      rapidly die by activation-induced cell death.

PMID- 11342626
TI  - p27kip protein levels and E2F activity are targets of Cot kinase during G1 phase
      progression in T cells.
AB  - Cot/Tpl-2 kinase, homologous to members of mitogen-activated protein kinase
      kinase kinase, was initially discovered by its capacity to promote cell
      transformation. Cot/Tpl-2 mRNA levels are increased during G(0) to G(1) phase
      progression in T lymphocytes, suggesting a role for this kinase later on in the
      cell cycle. The IL-2-dependent CTLL-2 cells were used to investigate the role of
      Cot kinase in G(1) to S phase transition. Transient expression of Cot kinase in
      CTLL-2 cells increases DNA synthesis triggered by IL-2 and the transient
      expression of a dominant negative form of Cot kinase in CTLL-2 markedly reduces
      the DNA synthesis triggered by this cytokine. Cell cycle analysis of synchronized
      CTLL-2 stabling overexpressing Cot kinase indicates that this kinase contributes
      to the passage to S and G(2)-M phases of the cell cycle. Cot kinase reduces the
      levels of the cyclin kinase inhibitor p27(kip), whereas bcl-x(L) expression is
      unaffected. Cot kinase also increases E2F transcriptional activity in a
      phosphatidylinositol 3 kinase-independent way and acts in synergy with this
      kinase. These data give evidence, for the first time, of the regulation of
      different G(1) progression events by Cot kinase.

PMID- 11342627
TI  - Role for transcription Pax5A factor in maintaining commitment to the B cell
      lineage by selective inhibition of granulocyte-macrophage colony-stimulating
      factor receptor expression.
AB  - During early B lymphopoiesis, developing B cells maintain lineage commitment
      despite the local presence of myeloid lineage-promoting cytokines such as GM-CSF
      and IL-3. Previous observations suggest that the B cell-specific transcription
      factor Pax5A (paired box 5A transcription factor) plays a role in maintaining B
      cell lineage commitment by limiting expansion and survival of early IL-3/GM-CSF
      dependent myeloid lineage cells. To define a mechanism by which Pax5A can exert
      these inhibitory effects on myeloid lineage differentiation, an inducible form of
      the Pax5A protein was expressed in the myeloid cell line FDC-P1. This cell line
      models myeloid progenitors in that it responds to the survival and growth
      potentiating effects of IL-3 and GM-CSF. We observed that enforced expression of
      Pax5A selectively suppressed proliferation in response to GM-CSF, but not IL-3.
      This effect was associated with specific down-regulation of GM-CSFR alpha-chain,
      but not beta-chain expression. These data provide a molecular mechanism to
      enforce commitment to the B cell lineage despite the presence of GM-CSF, a factor
      that has been shown to convert early developing B cells to the myeloid lineage.
      Furthermore, they indicate a role for B cell Pax5A expression in maintaining
      rather than directing commitment to the B cell lineage.

PMID- 11342628
TI  - Cell-associated ovalbumin is cross-presented much more efficiently than soluble
      ovalbumin in vivo.
AB  - To better understand the antigenic requirements for cross-presentation, we
      compared the in vivo efficiency of presentation of cell-associated vs soluble OVA
      with the OT-I (CD8) and OT-II (CD4) TCR transgenic lines. Cross-presentation of
      cell-associated OVA was very efficient, requiring as little as 21 ng of OVA to
      activate OT-II cells and 100-fold less to activate OT-I cells. In contrast,
      soluble OVA was presented inefficiently, requiring at least 10,000 ng OVA for
      activation of either T cell subset. Thus, cell-associated OVA was presented 500
      fold more efficiently than soluble OVA to CD4 T cells and 50,000-fold more
      efficiently to CD8 T cells. These data, which represent the first quantitative in
      vivo analysis of cross-presentation, show that cell-associated OVA is very
      efficiently presented via the class I pathway.

PMID- 11342629
TI  - Stage-specific modulation of IFN-regulatory factor 4 function by Kruppel-type
      zinc finger proteins.
AB  - Optimal humoral responses depend on the activation of Ag-specific B cells,
      followed by their progression toward a fully differentiated phenotype.
      Acquisition of stage-appropriate patterns of gene expression is crucial to this
      differentiation program. However, the molecular mechanisms used by B cells to
      modulate gene expression as they complete their maturation program are poorly
      understood. IFN-regulatory factor 4 (IRF-4) plays a critical role in mature B
      cell function. Using the transcriptional regulation of the human B cell
      activation marker CD23 as a model system, we have previously demonstrated that
      IRF-4 is induced in response to B cell-activating stimuli and that it acts as a
      transactivator of CD23 gene expression. We have furthermore found that IRF-4
      function can be blocked by B cell lymphomas 6 (BCL-6) protein, a Kruppel-type
      zinc finger repressor normally expressed in germinal center B cells. However,
      CD23 expression is known to be down-regulated in plasma cells despite high level
      expression of IRF-4 and the lack of BCL-6, suggesting that in plasma cells the
      IRF-4-mediated induction of CD23 is prevented by its interaction with a distinct
      repressor. In this set of studies, we demonstrate that IRF-4 interacts with B
      lymphocyte-induced maturation protein/positive regulatory domain I-binding factor
      1 (Blimp1/PRD1-BF1), a Kruppel-type zinc finger protein whose expression
      correlates with terminal B cell differentiation. Functional studies indicate that
      Blimp1, like BCL-6, can block IRF-4-transactivating ability. These findings thus
      support a model whereby IRF-4 function is modulated in a stage-specific manner by
      its interaction with developmentally restricted sets of Kruppel-type zinc finger
      proteins.

PMID- 11342630
TI  - Increasing the affinity for tumor antigen enhances bispecific antibody
      cytotoxicity.
AB  - We tested the hypothesis that bispecific Abs (Bsab) with increased binding
      affinity for tumor Ags augment retargeted antitumor cytotoxicity. We report that
      an increase in the affinity of Bsab for the HER2/neu Ag correlates with an
      increase in the ability of the Bsab to promote retargeted cytotoxicity against
      HER2/neu-positive cell lines. A series of anti-HER2/neu extracellular domain
      directed single-chain Fv fragments (scFv), ranging in affinity for HER2/neu from
      10(-7) to 10(-11) M, were fused to the phage display-derived NM3E2 human scFV:
      NM3E2 associates with the extracellular domain of human FcgammaRIII (CD16). The
      resulting series of Bsab promoted cytotoxicity of SKOV3 human ovarian carcinoma
      cells overexpressing HER2/neu by human PBMC preparations containing CD16-positive
      NK cells. The affinity for HER2/neu clearly influenced the ability of the Bsab to
      promote cytotoxicity of (51)Cr-labeled SKOV3 cells. Lysis was 6.5% with an anti
      HER2/neu K(D) = 1.7 x 10(-7) M, 14.5% with K(D) = 5.7 x 10(-9) M, and 21.3% with
      K(D) = 1.7 x 10(-10) M at 50:1 E:T ratios. These scFv-based Bsab did not cross
      link receptors and induce leukocyte calcium mobilization in the absence of tumor
      cell engagement. Thus, these novel Bsab structures should not induce the dose
      limiting cytokine release syndromes that have been observed in clinical trials
      with intact IgG BSAB: Additional manipulations in Bsab structure that improve
      selective tumor retention or facilitate the ability of Bsab to selectively cross
      link tumor and effector cells at tumor sites should further improve the utility
      of this therapeutic strategy.

PMID- 11342631
TI  - Lupus antibody bivalency is required to enhance prothrombin binding to
      phospholipid.
AB  - Lupus anticoagulants (LA) are a family of autoantibodies that are associated with
      in vitro anticoagulant activity but a strong predisposition to in vivo
      thrombosis. They are directed against plasma phospholipid-binding proteins
      including prothrombin. We have proposed that LA propagates coagulation in flowing
      blood by facilitating prothrombin interaction with the damaged blood vessel wall.
      A murine monoclonal anti-prothrombin Ab and three of three LA IgGs enhanced
      prothrombin binding to 75:25 phosphatidyl choline:phosphatidyl serine vesicles
      measured by either ultracentrifugation or right-angle light scattering. The
      assembly of prothrombin and LA IgG on phospholipid vesicles was estimated by
      surface plasmon resonance. The on rates for prothrombin and LA IgG were
      approximately the same as the on rate for prothrombin alone. In contrast, the off
      rates for prothrombin and LA IgG were 2- to 3-fold slower than the off rate for
      prothrombin. LA IgG bivalency was required for enhanced prothrombin binding to
      phospholipid vesicles, as Fab of the LA IgGs did not influence prothrombin
      binding at concentrations up to 40 microM. Modeling of the interactions of
      prothrombin, LA IgG and phospholipid vesicles indicated that augmentation of
      prothrombin binding to phospholipid vesicles by LA IgG could be accounted for by
      the bivalency of the LA IgG and the elevated microenvironmental concentration of
      prothrombin on the surface of phospholipid vesicles.

PMID- 11342632
TI  - Fundamental Ca2+ signaling mechanisms in mouse dendritic cells: CRAC is the major
      Ca2+ entry pathway.
AB  - Although Ca(2+)-signaling processes are thought to underlie many dendritic cell
      (DC) functions, the Ca(2+) entry pathways are unknown. Therefore, we investigated
      Ca(2+)-signaling in mouse myeloid DC using Ca(2+) imaging and
      electrophysiological techniques. Neither Ca(2+) currents nor changes in
      intracellular Ca(2+) were detected following membrane depolarization, ruling out
      the presence of functional voltage-dependent Ca(2+) channels. ATP, a purinergic
      receptor ligand, and 1-4 dihydropyridines, previously suggested to activate a
      plasma membrane Ca(2+) channel in human myeloid DC, both elicited Ca(2+) rises in
      murine DC. However, in this study these responses were found to be due to
      mobilization from intracellular stores rather than by Ca(2+) entry. In contrast,
      Ca(2+) influx was activated by depletion of intracellular Ca(2+) stores with
      thapsigargin, or inositol trisphosphate. This Ca(2+) influx was enhanced by
      membrane hyperpolarization, inhibited by SKF 96365, and exhibited a cation
      permeability similar to the Ca(2+) release-activated Ca(2+) channel (CRAC) found
      in T lymphocytes. Furthermore, ATP, a putative DC chemotactic and maturation
      factor, induced a delayed Ca(2+) entry with a voltage dependence similar to CRAC.
      Moreover, the level of phenotypic DC maturation was correlated with the
      extracellular Ca(2+) concentration and enhanced by thapsigargin treatment. These
      results suggest that CRAC is a major pathway for Ca(2+) entry in mouse myeloid DC
      and support the proposal that CRAC participates in DC maturation and migration.

PMID- 11342633
TI  - Transcriptional regulation of CD28 expression by CD28GR, a novel promoter element
      located in exon 1 of the CD28 gene.
AB  - CD28 provides an essential costimulatory signal required for Ag-mediated T cell
      activation via the TCR. Although accumulating evidence exists for the signaling
      properties of CD28, less is known regarding the regulation of CD28 expression. In
      this study, we have identified a novel promoter element of CD28, CD28GR
      (GGGGAGGAGGGG), which is located between +181 and +192 in exon 1 of the CD28
      gene. Mutations within the 12-bp CD28GR sequence abolished its transcriptional
      activity. CD28GR contains a Sp1/EGR-1 binding site, which was found to act as the
      predominant functional element for regulating CD28 gene expression in Jurkat
      cells. Exon 1/CD28GR-driven transcription in Jurkat cells was augmented by
      cotransfection with Sp1 or EGR-1 expression plasmid. Similar augmentation was
      also shown with pharmacologic activation. This study is the first to identify a
      regulatory element that is critical for conferring constitutive and activation
      induced transcriptional activation of the CD28 gene. Furthermore, our results
      proposed potential involvement of Sp1 in regulating CD28 expression. The linkage
      between Sp1 and the expression of CD28 has important implications in how viral
      infections, such as HIV, can induce immunosuppression.

PMID- 11342634
TI  - The exon A (C77G) mutation is a common cause of abnormal CD45 splicing in humans.
AB  - The leukocyte common (CD45) Ag is essential for normal T lymphocyte function and
      alternative splicing at the N terminus of the gene is associated with changes in
      T cell maturation and differentiation. Recently, a statistically significant
      association was reported in a large series of human thymus samples between
      phenotypically abnormal CD45 splicing and the presence of the CC chemokine
      receptor 5 deletion 32 (CCR5del32) allele, which confers resistance to HIV
      infection in homozygotes. We show here that abnormal splicing in these thymus
      samples is associated with the presence of the only established cause of CD45
      abnormal splicing, a C77G transversion in exon A. In addition we have examined
      227 DNA samples from peripheral blood of healthy donors and find no association
      between the exon A (C77G) and CCR5del32 mutations. Among 135 PBMC samples, tested
      by flow cytometric analysis, all those exhibiting abnormal splicing of CD45 also
      showed the exon A C77G transversion. We conclude that the exon A (C77G) mutation
      is a common cause of abnormal CD45 splicing and that further disease association
      studies of this mutation are warranted.

PMID- 11342635
TI  - Transcriptional regulation of intracellular IL-1 receptor antagonist gene by IL-1
      alpha in primary mouse keratinocytes.
AB  - The inflammatory cytokine IL-1alpha mediates inflammatory reactions in skin and
      up-regulates the expression of other proinflammatory genes. We previously found
      that IL-1alpha also increases steady state mRNA levels for intracellular IL-1
      receptor antagonist (icIL-1Ra) in primary mouse keratinocytes; however, the
      mechanism for this was unknown. Here we show that increased expression in primary
      keratinocytes is due to increased rates of transcription. To study the
      transcriptional regulation of icIL-1Ra expression induced by IL-1alpha, we
      functionally characterized 4.5 kb of the 5'-flanking region of the human icIL-1Ra
      gene. Deletion analysis showed that regulatory elements were contained in the 
      598- and -288-bp region upstream of the transcription start site. Then we
      investigated cis- and trans-acting factors required for icIL-1Ra expression and
      found that a NF-IL-6 site and a NF-kappaB site in the icIL-1Ra promoter were
      responsible for IL-1alpha-induced icIL-1Ra expression. Moreover, gel shift assays
      and cotransfection experiments showed that CCAAT/enhancer-binding proteins alpha,
      beta, and p65 bind to the NF-IL-6 site and NF-kappaB site, respectively, and
      functionally trans-activate the icIL-1Ra promoter. Finally, mutational analysis
      confirmed that these elements were both essential for maximal transcription
      induced by IL-1alpha.

PMID- 11342636
TI  - Multiple transcription factors regulate the inducible expression of the human
      complement receptor 2 promoter.
AB  - Complement receptor 2 (CR2) is regulated at the transcriptional level, but the
      promoter elements and the transcription factors that bind to them and contribute
      to its regulation are unknown. After documenting that PMA and cAMP induced the
      activity of the CR2 promoter by 10-fold, we conducted promoter truncation and
      mutagenesis experiments, in conjunction with shift assays, to determine the
      functionally important regions of the promoter and the proteins that bind to
      them. We identified two regions, separated by approximately 900 nucleotides,
      which together were responsible for inducible promoter activity. Mutagenesis of
      single promoter elements demonstrated a functional upstream stimulatory factor/E
      box in the TATA box-proximal region and three equally important, closely spaced,
      CREB/AP-1 half-sites in the upstream promoter region. The cAMP response element
      binding protein (CREB)/AP-1 half-sites bound in vitro Jun and CREB that are
      induced by protein kinases A and/or C. The 900-nucleotide segment stretching
      between the above two regions had no functional impact on the induced
      transcription, and its deletion increased the promoter activity. Finally, a
      region upstream of the distal site had a repressor activity on CR2 transcription.
      Moreover, IL-4 induced binding of CREB and AP-1 to the upstream promoter elements
      and resulted in increased CR2 surface protein expression. These studies have
      characterized regions of the CR2 promoter and the transcription factors that bind
      to them and are crucial to induced CR2 expression. Our studies may provide
      insights to novel approaches to modulate B cell function by regulating CR2 gene
      transcription.

PMID- 11342637
TI  - Characteristics of HIV-1 Nef regions containing multiple CD8+ T cell epitopes:
      wealth of HLA-binding motifs and sensitivity to proteasome degradation.
AB  - First and foremost among the many factors that influence epitope presentation are
      the degradation of Ag, which results in peptide liberation, and the presence of
      HLA class I molecules able to present the peptides to T lymphocytes. To define
      the regions of HIV-1 Nef that can provide multiple T cell epitopes, we analyzed
      the Nef sequence and determined that there are 73 peptides containing 81 HLA
      binding motifs. We tested the binding of these peptides to six common HLA
      molecules (HLA-A2, -A3, -A24, -B7, -B8, and -B35), and we showed that most of
      them were efficient binders (54% of motifs), especially peptides associating with
      HLA-A3, -B7/35, and -B8 molecules. Nef peptides most frequently recognized by T
      cells of HIV-1-infected individuals were 90-97, 135-143, 71-81, 77-85, 90-100, 73
      82, and 128-137. The frequency of T cell recognition was not directly related to
      the strength of peptide-HLA binding. The generation of Nef epitopes is crucial;
      therefore, we investigated the digestion by the 20S proteasome of a large
      peptide, Nef(66-100). This fragment was efficiently cleaved, and NH(2)-terminally
      extended precursors of epitope 71-81 were recognized by T cells of an HIV-1
      infected individual. These results suggest that a high frequency of T cell
      recognition may depend on proteasome cleavage.

PMID- 11342638
TI  - RNA-dependent protein kinase PKR is required for activation of NF-kappa B by IFN
      gamma in a STAT1-independent pathway.
AB  - The IFN-inducible dsRNA-activated protein kinase PKR regulates protein synthesis
      through phosphorylation of eukaryotic initiation factor-2alpha. It also acts as a
      signal transducer for transcription factors NF-kappaB, IFN regulatory factor-1,
      and activating transcription factor-2. IFN-gamma, a pleiotropic cytokine, elicits
      gene expression by activating the Janus kinase-STAT signaling pathway. IFN-gamma
      can synergize with TNF-alpha to activate NF-kappaB in a number of cell lines.
      Here we show that IFN-gamma alone can activate NF-kappaB, by a Janus kinase-1
      mediated, but Stat1-independent, mechanism. NF-kappaB activation by IFN-gamma is
      associated with degradation of IkappaB beta. The IFN-gamma response can be
      blocked by 2',5'-oligoadenylate-linked antisense chimeras against PKR mRNA. There
      was no activation of NF-kappaB by IFN in PKR-null cells, indicating that PKR is
      required for IFN-gamma signaling to NF-kappaB.

PMID- 11342639
TI  - Positive and negative roles of the trans-acting T cell factor-1 for the
      acquisition of distinct Ly-49 MHC class I receptors by NK cells.
AB  - Members of the Ly-49 gene family code for class I MHC-specific receptors that
      regulate NK cell function. Due to a combinatorial distribution of Ly-49
      receptors, NK cells display considerable clonal heterogeneity. The acquisition of
      one Ly-49 receptor, Ly-49A is strictly dependent on the transcriptional trans
      acting factor T cell-specific factor-1 (TCF-1). Indeed, TCF-1 binds to two sites
      in the Ly-49a promoter and regulates its activity, suggesting that the Ly-49a
      gene is a direct TCF-1 target. TCF-1 deficiency resulted in the altered usage of
      additional Ly-49 receptors. We show in this study, using TCF-1 beta(2)
      microglobulin double-deficient mice, that these repertoire alterations are not
      due to Ly-49/MHC class I interactions. Our findings rather suggest a TCF-1
      dependent, cell autonomous effect on the acquisition of multiple Ly-49 receptors.
      Besides reduced receptor usage (Ly-49A and D), we also observed no effect (Ly
      49C) and significantly expanded (Ly-49G and I) receptor usage in the absence of
      TCF-1. These effects did not in all cases correlate with the presence of TCF
      binding sites in the respective proximal promoter. Therefore, besides TCF-1
      binding to the proximal promoter, Ly-49 acquisition may also be regulated by TCF
      1 binding to more distant cis-acting elements and/or by regulating the expression
      of additional trans-acting factors. Consistent with the observed differential,
      positive or negative role of TCF-1 for Ly-49 receptor acquisition, reporter gene
      assays revealed the presence of an inducing as well as a repressing TCF site in
      certain proximal Ly-49 promoters. These findings reveal an important role of TCF
      1 for the formation of the NK cell receptor repertoire.

PMID- 11342640
TI  - A prominent role for activator protein-1 in the transcription of the human 2B4
      (CD244) gene in NK cells.
AB  - The cell surface glycoprotein 2B4 (CD244) of the Ig superfamily is involved in
      the regulation of NK and T lymphocyte functions. We have recently identified CD48
      as the high affinity counterreceptor for 2B4 in both mice and humans. The
      cytoplasmic domain of 2B4 associates with src homology 2 domain-containing
      protein or signaling lymphocyte activation molecule-associated protein, whose
      mutation is the underlying genetic defect in the X-linked lymphoproliferative
      syndrome. In this study, we report the molecular cloning and characterization of
      the human 2B4 (h2B4) promoter. Through primer extension analysis, we found that
      the transcription of the h2B4 gene initiates at multiple start sites. We isolated
      h2B4 genomic clones and PCR amplified the 5' untranslated region containing the
      promoter elements. We have identified a functional AP-1 site that lies between (
      106 to -100) through transient transfection analysis in YT cells, a human NK cell
      line. EMSAs with Abs specific for various protein factors of the AP-1 family
      revealed that multiple members of the Jun family are involved in the regulation
      of the h2B4 gene. Mutation of the AP-1 site not only abolishes protein/DNA
      interactions but also promoter activity. These results demonstrate a significant
      role for AP-1 in the transcriptional regulation of the h2B4 gene.

PMID- 11342641
TI  - Characterization of mouse carboxypeptidase N small active subunit gene structure.
AB  - Carboxypeptidase N (CPN) is a plasma zinc metalloprotease comprised of two small
      subunits that have enzymatic activity, and two large subunits, which protect the
      enzyme from degradation. CPN cleaves the carboxyl-terminal amino acids arginine
      and lysine from biologically active peptides such as complement anaphylatoxins,
      kinins, and fibrinopeptides. To delineate the murine CPN small subunit coding
      region, gene structure, and chromosome location, cDNA and genomic clones were
      isolated, characterized, and used in Northern and fluorescence in situ
      hybridization analyses. The results from this study demonstrate that the murine
      CPN small subunit gene is a single copy gene of approximately 29 kb that is
      transcribed in the liver into a 1793-bp mRNA with an open reading frame of 1371
      nucleotides encoding 457 aa. The gene contains nine exons ranging in size from
      455 bp (exon 1) to 100 bp (exon 7), and eight introns ranging in size from 6.2 kb
      (intron 2) to 1.4 kb (intron 4). All intron/exon junctions follow the normal
      consensus rule. The mouse CPN small subunit gene localized to chromosomal band
      19D2, which is syntenic to human chromosome 10q23-25. Primer extension
      experiments using mouse liver mRNA indicate one major transcriptional initiation
      site and three minor sites. Sequence analysis of the 5'-flanking region indicated
      a TATA-less promoter and numerous transcription factor binding sites, which may
      confer liver-specific expression of the CPN small subunit gene.

PMID- 11342642
TI  - Culture at high density improves the ability of human macrophages to control
      mycobacterial growth.
AB  - The mechanisms through which granuloma formation helps control mycobacterial
      infection are poorly understood, but it is possible that the accumulation of
      macrophages at high density at sites of infection promotes the differentiation of
      macrophages into cells with improved mycobactericidal activity. To test this
      possibility, varying numbers of monocytes were cultured in 96-well plates for 3
      days, infected with Mycobacterium bovis bacillus Calmette-Guerin, and
      mycobacterial number was assessed 7 days after infection based on the measurement
      of luciferase activity expressed by a mycobacterial reporter strain or by
      counting CFU. Mycobacterial growth was optimal in cultures containing 5 x 10(4)
      cells/well, but increasing the number of cells to 2 x 10(5) cells/well resulted
      in complete inhibition of mycobacterial growth. This effect could not be
      explained by differences in mycobacterial uptake, multiplicity of infection,
      acidification of the extracellular medium in high density cultures, enhanced NO
      production, or paracrine stimulation resulting from secretion of cytokines or
      other proteins. The morphology of cells cultured at high density was strikingly
      different from that of monocytes cultured at 5 x 10(4) cells/well, including the
      appearance of numerous giant cells. The bacteriostatic activity of monocyte
      derived macrophages was also dependent on cell number, but fewer of these more
      mature cells were required to control mycobacterial growth. Thus, the ability of
      human macrophages to control mycobacterial infection in vitro is influenced by
      the density of cells present, findings that may help explain why the formation of
      granulomas in vivo appears to be a key event in the control of mycobacterial
      infections.

PMID- 11342643
TI  - Combined treatment of a murine breast cancer model with type 5 adenovirus vectors
      expressing murine angiostatin and IL-12: a role for combined anti-angiogenesis
      and immunotherapy.
AB  - In this study, we used intratumor delivery of adenoviral vectors to induce a
      selective anti-tumor response by combining the potent angiogenesis inhibitor
      murine angiostatin (adenovirus (Ad)-angiostatin) with the powerful immune
      simulator and angiostatic cytokine murine IL-12 (Ad-IL-12). In a murine model of
      breast carcinoma, intratumor injection of Ad-angiostatin delayed mean tumor
      growth, as compared with control virus with an initial regression of tumor
      growth, in 65% of treated animals. However, all treated animals eventually
      succumbed to the tumors. Mice injected with Ad-IL-12 alone responded with an
      initial regression in 20% of treated animals, with only 13% developing a total
      regression. Coinjection of the vectors resulted in 96% of the treated animals
      developing an initial regression, with 54% undergoing a total regression of the
      tumor. These mice were resistant to tumor rechallenge and developed a strong CTL
      response. Frozen tumor sections were stained for microvessel density using an Ab
      against murine CD31, an endothelial cell marker. Automated image analysis
      revealed the mean microvessel density following the administration of Ad
      angiostatin and Ad-IL-12 alone or in combination was significantly reduced
      compared with the control-treated tumor. In summary, we have shown that a short
      term course of antiangiogenic therapy combined with immunotherapy can effectively
      shrink a solid tumor and vaccinate the animal against rechallenge. The rationale
      for this therapy is to limit the tumor size by attacking the vasculature with
      angiostatin, thereby allowing IL-12 to mount a T cell-specific response against
      the tumor AG:

PMID- 11342644
TI  - Enhancement of Sindbis virus self-replicating RNA vaccine potency by linkage of
      Mycobacterium tuberculosis heat shock protein 70 gene to an antigen gene.
AB  - Recently, self-replicating RNA vaccines (RNA replicons) have emerged as an
      effective strategy for nucleic acid vaccine development. Unlike naked DNA
      vaccines, RNA replicons eventually cause lysis of transfected cells and therefore
      do not raise the concern of integration into the host genome. We evaluated the
      effect of linking human papillomavirus type 16 E7 as a model Ag to Mycobacterium
      tuberculosis heat shock protein 70 (HSP70) on the potency of Ag-specific immunity
      generated by a Sindbis virus self-replicating RNA vector, SINrep5. Our results
      indicated that this RNA replicon vaccine containing an E7/HSP70 fusion gene
      generated significantly higher E7-specific T cell-mediated immune responses in
      vaccinated mice than did vaccines containing the wild-type E7 gene. Furthermore,
      our in vitro studies demonstrated that E7 Ag from E7/HSP70 RNA replicon
      transfected cells can be processed by bone marrow-derived dendritic cells and
      presented more efficiently through the MHC class I pathway than can wild-type E7
      RNA replicon-transfected cells. More importantly, the fusion of HSP70 to E7
      converted a less effective vaccine into one with significant potency against E7
      expressing tumors. This antitumor effect was dependent on NK cells and CD8(+) T
      cells. These results indicated that fusion of HSP70 to an Ag gene may greatly
      enhance the potency of self-replicating RNA vaccines.

PMID- 11342645
TI  - Vaccination with the T cell antigen Mtb 8.4 protects against challenge with
      Mycobacterium tuberculosis.
AB  - The development of an effective vaccine against Mycobacterium tuberculosis is a
      research area of intense interest. Mounting evidence suggests that protective
      immunity to M. tuberculosis relies on both MHC class II-restricted CD4(+) T cells
      and MHC class I-restricted CD8(+) T cells. By purifying polypeptides present in
      the culture filtrate of M. tuberculosis and evaluating these molecules for their
      ability to stimulate PBMC from purified protein derivative-positive healthy
      individuals, we previously identified a low-m.w. immunoreactive T cell Ag, Mtb
      8.4, which elicited strong Th1 T cell responses in healthy purified protein
      derivative-positive human PBMC and in mice immunized with recombinant Mtb 8.4.
      Herein we report that Mtb 8.4-specific T cells can be detected in mice immunized
      with the current live attenuated vaccine, Mycobacterium bovis-bacillus Calmette
      Guerin as well as in mice infected i.v. with M. tuberculosis. More importantly,
      immunization of mice with either plasmid DNA encoding Mtb 8.4 or Mtb 8.4
      recombinant protein formulated with IFA elicited strong CD4(+) T cell and CD8(+)
      CTL responses and induced protection on challenge with virulent M. tuberculosis.
      Thus, these results suggest that Mtb 8.4 is a potential candidate for inclusion
      in a subunit vaccine against TB.

PMID- 11342646
TI  - A critical role of Fc receptor-mediated antibody-dependent phagocytosis in the
      host resistance to blood-stage Plasmodium berghei XAT infection.
AB  - Plasmodium berghei XAT is an irradiation-induced attenuated variant derived from
      the lethal strain P. berghei NK65, and its blood-stage parasites are
      spontaneously cleared in immune competent mice. In the present study, we studied
      the mechanism of host resistance to blood-stage malaria infection using P.
      berghei XAT. Infection enhanced Ab-dependent phagocytosis of PRBC by splenic
      macrophages in wild-type C57BL/6 mice. In contrast, FcR gamma-chain knockout
      (FcRgamma(-/-)) mice, which lack the ability to mediate Ab-dependent phagocytosis
      and Ab-dependent cell-mediated cytotoxicity through FcgammaRI, FcgammaRII, and
      FcgammaRIII, could not induce Ab-dependent phagocytic activity. These FcRgamma(-/
      ) mice showed increased susceptibility to the P. berghei XAT infection, with
      eventually fatal results, although they produced comparable amounts of IFN-gamma
      by spleen cells and anti-XAT Abs in serum. In addition, passive transfer of anti
      XAT IgG obtained from wild-type mice that had recovered from infection into
      FcRgamma(-/-) mice could not suppress the increase in parasitemia, and almost all
      of these mice died after marked parasitemia. In contrast, passive transfer of
      anti-XAT IgG into control wild-type mice inhibited the increase in parasitemia.
      IFN-gamma(-/-) mice, which were highly susceptible to the P. berghei XAT
      infection, failed to induce Ab-dependent phagocytic activity and also showed
      reduced production of serum anti-XAT IgG2a isotype compared with control wild
      type mice. These results suggest that FcR-mediated Ab-dependent phagocytosis,
      which is located downstream of IFN-gamma production, is important as an effector
      mechanism to eliminate PRBC in blood-stage P. berghei XAT infection.

PMID- 11342647
TI  - Herpes simplex inhibits the capacity of lymphoblastoid B cell lines to stimulate
      CD4+ T cells.
AB  - HSV establish a lifelong persistent infection in their host even among
      immunocompetent persons. The viruses use a variety of immune evasion strategies,
      presumably to assist persistent replication in the human host. We have observed
      that infection of human B lymphoblastoid cells (B-LCL) by HSV resulted in a
      strong inhibition of their ability to induce CD4(+) T cell clone proliferation
      and cytokine secretion. This inhibitory effect occurs in a variety of both HSV-
      and HIV-specific clones from three different patients. The inhibition is observed
      when the Ag is provided either as a soluble protein or as a synthetic peptide and
      is not associated with detectable down-modulation of the MHC class II molecules
      or costimulatory molecules. Expression of the HSV-1 unique sequence 1 gene (US1)
      is necessary and sufficient to induce this inhibition of APC function. US1 gene
      expression also made B-LCL less susceptible to CD4(+) T cell-mediated lysis.
      These data indicate a novel immune evasion strategy by HSV-1 in which Ag
      processing cells that become infected by HSV-1 are inhibited in their ability to
      induce subsequent CD4(+) T cell activation.

PMID- 11342648
TI  - Activity of human IgG and IgA subclasses in immune defense against Neisseria
      meningitidis serogroup B.
AB  - Both IgG and IgA Abs have been implicated in host defense against bacterial
      infections, although their relative contributions remain unclear. We generated a
      unique panel of human chimeric Abs of all human IgG and IgA subclasses with
      identical V genes against porin A, a major subcapsular protein Ag of Neisseria
      meningitidis and a vaccine candidate. Chimeric Abs were produced in baby hamster
      kidney cells, and IgA-producing clones were cotransfected with human J chain
      and/or human secretory component. Although IgG (isotypes IgG1-3) mediated
      efficient complement-dependent lysis, IgA was unable to. However, IgA proved
      equally active to IgG in stimulating polymorphonuclear leukocyte respiratory
      burst. Remarkably, although porin-specific monomeric, dimeric, and polymeric IgA
      triggered efficient phagocytosis, secretory IgA did not. These studies reveal
      unique and nonoverlapping roles for IgG and IgA Abs in defense against
      meningococcal infections.

PMID- 11342649
TI  - Secretory IgA specific for a conserved epitope on gp41 envelope glycoprotein
      inhibits epithelial transcytosis of HIV-1.
AB  - As one of the initial mucosal transmission pathways of HIV (HIV-1), epithelial
      cells translocate HIV-1 from apical to basolateral surface by nondegradative
      transcytosis. Transcytosis is initiated when HIV-1 envelope glycoproteins bind to
      the epithelial cell membrane. Here we show that the transmembrane gp41 subunit of
      the viral envelope binds to the epithelial glycosphingolipid galactosyl ceramide
      (Gal Cer), an alternative receptor for HIV-1, at a site involving the conserved
      ELDKWA epitope. Disrupting the raft organization of the Gal Cer-containing
      microdomains at the apical surface inhibited HIV-1 transcytosis. Immunological
      studies confirmed the critical role of the conserved ELDKWA hexapeptide in HIV-1
      transcytosis. Mucosal IgA, but not IgG, from seropositive subjects targeted the
      conserved peptide, neutralized gp41 binding to Gal Cer, and blocked HIV-1
      transcytosis. These results underscore the important role of secretory IgA in
      designing strategies for mucosal protection against HIV-1 infection.

PMID- 11342650
TI  - Extrafollicular plasmablast B cells play a key role in carrying retroviral
      infection to peripheral organs.
AB  - B cells can either differentiate in germinal centers or in extrafollicular
      compartments of secondary lymphoid organs. Here we show the migration properties
      of B cells after differentiation in murine peripheral lymph node infected with
      mouse mammary tumor virus. Naive B cells become activated, infected, and carry
      integrated retroviral DNA sequences. After production of a retroviral
      superantigen, the infected B cells receive cognate T cell help and differentiate
      along the two main differentiation pathways analogous to classical Ag responses.
      The extrafollicular differentiation peaks on day 6 of mouse mammary tumor virus
      infection, and the follicular one becomes detectable after day 10. B cells
      participating in this immune response carry a retroviral DNA marker that can be
      detected by using semiquantitative PCR. We determined the migration patterns of B
      cells having taken part in the T cell-B cell interaction from the draining lymph
      node to different tissues. Waves of immigration and retention of infected cells
      in secondary lymphoid organs, mammary gland, salivary gland, skin, lung, and
      liver were observed correlating with the two peaks of B cell differentiation in
      the draining lymph node. Other organs revealed immigration of infected cells at
      later time points. The migration properties were correlated with a strong up
      regulation of alpha(4)beta(1) integrin expression. These results show the
      migration properties of B cells during an immune response and demonstrate that a
      large proportion of extrafolliculary differentiating plasmablasts can escape
      local cell death and carry the retroviral infection to peripheral organs.

PMID- 11342651
TI  - ATP-mediated killing of Mycobacterium bovis bacille Calmette-Guerin within human
      macrophages is calcium dependent and associated with the acidification of
      mycobacteria-containing phagosomes.
AB  - We previously demonstrated that extracellular ATP stimulated macrophage death and
      mycobacterial killing within Mycobacterium bovis Bacille Calmette-Guerin (BCG)
      infected human macrophages. ATP increases the cytosolic Ca(2+) concentration in
      macrophages by mobilizing intracellular Ca(2+) via G protein-coupled P2Y
      receptors, or promoting the influx of extracellular Ca(2+) via P2X purinoceptors.
      The relative contribution of these receptors and Ca(2+) sources to ATP-stimulated
      macrophage death and mycobacterial killing was investigated. We demonstrate that
      1) ATP mobilizes Ca(2+) in UTP-desensitized macrophages (in Ca(2+)-free medium)
      and 2) UTP but not ATP fails to deplete the intracellular Ca(2+) store,
      suggesting that the pharmacological properties of ATP and UTP differ, and that a
      Ca(2+)-mobilizing P2Y purinoceptor in addition to the P2Y(2) subtype is expressed
      on human macrophages. ATP and the Ca(2+) ionophore, ionomycin, promoted
      macrophage death and BCG killing, but ionomycin-mediated macrophage death was
      inhibited whereas BCG killing was largely retained in Ca(2+)-free medium.
      Pretreatment of cells with thapsigargin (which depletes inositol (1,4,5)
      trisphosphate-mobilizable intracellular stores) or 1,2-bis-(2-aminophenoxy)ethane
      N, N, N',N'-tetraacetic acid acetoxymethyl ester (an intracellular Ca(2+)
      chelator) failed to inhibit ATP-stimulated macrophage death but blocked
      mycobacterial killing. Using the acidotropic molecular probe, 3-(2,4
      dinitroanilino)-3'-amino-N-methyl dipropylamine, it was revealed that ATP
      stimulation promoted the acidification of BCG-containing phagosomes within human
      macrophages, and this effect was similarly dependent upon Ca(2+) mobilization
      from intracellular stores. We conclude that the cytotoxic and bactericidal
      effects of ATP can be uncoupled and that BCG killing is not the inevitable
      consequence of death of the host macrophage.

PMID- 11342652
TI  - Cell density regulates neutrophil IL-8 synthesis: role of IL-1 receptor
      antagonist and soluble TNF receptors.
AB  - Although cytokine synthesis in polymorphonuclear leukocytes (PMN) was shown to be
      modulated by soluble mediators, the impact of microenvironmental conditions has
      not been elucidated. In this study, we investigated the effect of cell density on
      cytokine release from human neutrophils. PMN were cultured at various cell
      densities (10 x 10(6) PMN/ml; 60 x 10(6) PMN/ml), and LPS-induced release of
      cytokines was quantified by ELISA technique. Upon an increase in PMN density,
      secretion of the CXC chemokine IL-8 was progressively reduced. This effect was
      paralleled by a decrease in IL-8 mRNA. In contrast, TNF-alpha and IL-1beta rose
      proportionally with increasing cell density. The inhibition of IL-8 secretion was
      reproduced by conditioned media of PMN at high cell density, but was not affected
      by blocking beta(2) integrin-dependent adhesion. When analyzing the supernatant
      of LPS-challenged neutrophils, large amounts of soluble TNFRs p55 and p75
      (sTNFRI, sTNFRII), and IL-1R antagonist (IL-1RA), rising constantly with the cell
      density, were detected. Interestingly, combined blocking of the bioactivities of
      these mediators completely restored neutrophil IL-8 secretion at high cell
      densities, with the anti-IL-1RA Ab being the more potent agent. Moreover,
      combined application of exogenous IL-1RA and sTNFRs to 10 x 10(6) PMN/ml
      reproduced the suppression of IL-8 generation. We conclude that neutrophil IL-8
      synthesis is autoregulated, being suppressed under conditions of high cell
      density. IL-1RA and sTNFRs, accumulating under these circumstances, seem to be
      centrally involved in this regulatory mechanism by interfering with the IL-1beta-
      and TNF-alpha-dependent IL-8 generation. This feedback mechanism may control
      further neutrophil recruitment and activation in a neutrophil-rich environment,
      thereby preventing tissue destruction.

PMID- 11342653
TI  - A potential role for annexin 1 as a physiologic mediator of glucocorticoid
      induced L-selectin shedding from myeloid cells.
AB  - Glucocorticoids can dampen inflammatory responses by inhibiting neutrophil
      recruitment to tissue sites. The detailed mechanism by which glucocorticoids
      exert this affect on neutrophils is unknown. L-selectin is a leukocyte cell
      surface receptor that is implicated in several steps of neutrophil recruitment.
      Recently, several studies have shown that systemic treatment of animals and
      humans with glucocorticoids induces decreased L-selectin expression on
      neutrophils, suggesting one mechanism by which inflammation may be negatively
      regulated. However, when neutrophils are treated in vitro with glucocorticoids,
      no effect on L-selectin expression is observed. Thus, the existence of an
      additional mediator is plausible. In this study, we investigate whether annexin 1
      (ANX1), a recognized second messenger of glucocorticoids, could be such a
      mediator. We show that ANX1 induces a dose- and time-dependent decrease in L
      selectin expression on both peripheral blood neutrophils and monocytes but has no
      effect on lymphocytes. The loss of L-selectin from neutrophils is due to shedding
      that is mediated by a cell surface metalloprotease ("sheddase"). Using cell shape
      and a beta(2) integrin activation epitope, we show that the ANX1-induced shedding
      of L-selectin appears to occur without overt cell activation. These data may
      provide the basis for further understanding of mechanisms involved in the down
      regulation of inflammatory responses.

PMID- 11342654
TI  - Reactive nitrogen species inhibit alveolar epithelial fluid transport after
      hemorrhagic shock in rats.
AB  - Our recent experimental work demonstrated that a neutrophil-dependent
      inflammatory response in the lung prevented the normal up-regulation of alveolar
      fluid clearance by catecholamines following hemorrhagic shock. In this study, we
      tested the hypothesis that the release of NO within the airspaces of the lung was
      responsible for the shock-mediated failure of the alveolar epithelium to respond
      to catecholamines in rats. Hemorrhagic shock was associated with an inducible NO
      synthase (iNOS)-dependent increase in the lung production of NO and a failure of
      the alveolar epithelium to up-regulate vectorial fluid transport in response to
      beta-adrenergic agonists. Inhibition of iNOS restored the normal catecholamine
      mediated up-regulation of alveolar liquid clearance. Airspace instillation of
      dibutyryl cAMP, a stable analog of cAMP, restored the normal fluid transport
      capacity of the alveolar epithelium after prolonged hemorrhagic shock, whereas
      direct stimulation of adenyl cyclase by forskolin had no effect. Pretreatment
      with pyrrolidine dithiocarbamate or sulfasalazine attenuated the iNOS-dependent
      production of NO in the lung and restored the normal up-regulation of alveolar
      fluid clearance by catecholamines after prolonged hemorrhagic shock. Based on in
      vitro studies with an alveolar epithelial cell line, A549 cells, the effect of
      sulfasalazine appeared to be mediated in part by inhibition of NF-kappaB
      activation, and the protective effect was mediated by the inhibition of
      IkappaBalpha protein degradation. In summary, these results provide the first in
      vivo evidence that NO, released within the airspaces of the lung probably
      secondary to the NF-kappaB-dependent activation of iNOS, is a major proximal
      inflammatory mediator that limits the rate of alveolar epithelial transport after
      prolonged hemorrhagic shock by directly impairing the function of membrane
      proteins involved in the beta-adrenergic receptor-cAMP signaling pathway in
      alveolar epithelium.

PMID- 11342655
TI  - Role of p190RhoGAP in beta 2 integrin regulation of RhoA in human neutrophils.
AB  - We found that engagement of beta(2) integrins on human neutrophils induced
      activation of RhoA, as indicated by the increased ratio of GTP:GTP + GDP
      recovered on RhoA and translocation of RhoA to a membrane fraction. The
      clustering of beta(2) integrins also induced a time-dependent increase in GDP
      bound to RhoA, which correlated with beta(2) integrin-induced activation of
      p190RHOGAP: The activation of p190RhoGAP was completely blocked by [4-amino-5-(4
      methylphenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine] (PP1), a selective inhibitor
      of Src family tyrosine kinases. However, clustering of beta(2) integrins did not
      increase the basal tyrosine phosphorylation of p190RhoGAP, nor did it affect the
      amount of p120RasGAP bound to p190RHOGAP: Instead, the beta(2) integrin-induced
      activation of p190RhoGAP was accompanied by increased tyrosine phosphorylation of
      a p190RhoGAP-associated protein, p120RasGAP, and accumulation of both p120RasGAP
      and p190RhoGAP in a membrane fraction. PP1 blocked the beta(2) integrin-induced
      phosphorylation of p120RasGAP, as well as the translocation of p190RhoGAP and
      p120RasGAP, but it did not affect the accumulation of RhoA in the membrane
      fraction. In agreement with the mentioned findings, PP1 also increased the
      GTP:GTP + GDP ratio recovered on RhoA immunoprecipitated from beta(2) integrin
      stimulated cells. Thus, in neutrophils, beta(2) integrin-induced activation of
      p190RhoGAP requires a signal from a Src family tyrosine kinase, but it does not
      occur via the signaling pathway responsible for activation of RHOA:

PMID- 11342656
TI  - IL-10-deficient mice demonstrate multiple organ failure and increased mortality
      during Escherichia coli peritonitis despite an accelerated bacterial clearance.
AB  - To determine the role of endogenous IL-10 in local antibacterial host defense and
      in the development of a systemic inflammatory response syndrome during abdominal
      sepsis, IL-10 gene-deficient (IL-10(-/-)) and wild-type (IL-10(+/+)) mice
      received an i.p. injection with Escherichia coli. Peritonitis was associated with
      a bacterial dose-dependent increase in IL-10 concentrations in peritoneal fluid
      and plasma. The recovery of E. coli from the peritoneal fluid, blood, and lungs
      was diminished in IL-10(-/-) mice, indicating that endogenous IL-10 impaired
      bacterial clearance. Despite a lower bacterial load, IL-10(-/-) mice had higher
      concentrations of TNF, macrophage inflammatory protein-2 and keratinocyte in
      peritoneal fluid and plasma, and demonstrated more severe multiple organ damage
      as indicated by clinical chemistry and histopathology. Furthermore, IL-10(-/-)
      mice showed an increased neutrophil recruitment to the peritoneal cavity. To
      examine the role of elevated TNF levels in the altered host response in IL-10(-/
      ) mice, the effect of a neutralizing anti-TNF mAb was determined. Anti-TNF did
      not influence the clearance of E. coli in either IL-10(+/+) or IL-10(-/-) mice.
      Furthermore, anti-TNF did not affect leukocyte influx in the peritoneal fluid,
      multiple organ damage, or survival in IL-10(+/+) mice. In IL-10(-/-) mice, anti
      TNF partially attenuated neutrophil recruitment and multiple organ damage, and
      prevented the increased lethality. These data suggest that although endogenous IL
      10 facilitates the outgrowth and dissemination of bacteria during E. coli
      peritonitis, it protects mice from lethality by attenuating the development of a
      systemic inflammatory response syndrome by a mechanism that involves inhibition
      of TNF release.

PMID- 11342657
TI  - Antioxidants inhibit indoleamine 2,3-dioxygenase in IFN-gamma-activated human
      macrophages: posttranslational regulation by pyrrolidine dithiocarbamate.
AB  - Induction of the heme-containing indoleamine 2,3-dioxygenase (IDO) by IFN-gamma
      is implicated in anti-microbial and pro-inflammatory activities of human
      macrophages. Antioxidants can modulate the expression of immune and inflammatory
      genes, and pyrrolidine dithiocarbamate (PDTC) is a frequently used antioxidant to
      inhibit the transcription factor NF-kappaB. Here we show that IFN-gamma treatment
      of human monocyte-derived macrophages (hMDMs) increased the proportion of
      oxidized glutathione. PDTC attenuated this increase and inhibited IDO activity,
      although it increased IDO protein expression and did not affect IDO mRNA
      expression and enzyme activity directly. Other antioxidants, 2-ME, ebselen, and t
      butyl hydroquinone, inhibited IDO protein expression. Similar to PDTC, the heme
      biosynthesis inhibitor succinylacetone (SA) and the iron-chelator pyridoxal
      isonicotinoyl hydrazone inhibited cellular IDO activity without affecting protein
      expression, whereas addition of hemin or the heme precursor delta-aminolevulinic
      acid increased IDO activity. Also, incubation of IFN-gamma-activated hMDM with
      delta-[(14)C]-aminolevulinic acid resulted in the incorporation of label into
      immunoprecipitated IDO, a process inhibited by PDTC and SA. Furthermore,
      supplementation of lysates from PDTC- or SA-treated hMDM with hemin fully
      restored IDO activity to control levels, and hemin also reversed the inhibitory
      action of SA but not PDTC in intact cells. Together these results establish a
      requirement for de novo heme synthesis for IDO activity in IFN-gamma-activated
      hMDM. They show that, similar to other pro-inflammatory proteins, the activity of
      IDO is modulated by antioxidants though in the case of PDTC this takes place
      posttranslationally, in part by limiting the availability of heme for the
      formation of holo-IDO.

PMID- 11342658
TI  - Identification of a selective nonpeptide antagonist of the anaphylatoxin C3a
      receptor that demonstrates antiinflammatory activity in animal models.
AB  - The anaphylatoxin C3a is a potent chemotactic peptide and inflammatory mediator
      released during complement activation which binds to and activates a G-protein
      coupled receptor. Molecular cloning of the C3aR has facilitated studies to
      identify nonpeptide antagonists of the C3aR. A chemical lead that selectively
      inhibited the C3aR in a high throughput screen was identified and chemically
      optimized. The resulting antagonist, N(2)-[(2,2-diphenylethoxy)acetyl]-L-arginine
      (SB 290157), functioned as a competitive antagonist of (125)I-C3a radioligand
      binding to rat basophilic leukemia (RBL)-2H3 cells expressing the human C3aR (RBL
      C3aR), with an IC(50) of 200 nM. SB 290157 was a functional antagonist, blocking
      C3a-induced C3aR internalization in a concentration-dependent manner and C3a
      induced Ca(2+) mobilization in RBL-C3aR cells and human neutrophils with IC(50)s
      of 27.7 and 28 nM, respectively. SB 290157 was selective for the C3aR in that it
      did not antagonize the C5aR or six other chemotactic G protein-coupled receptors.
      Functional antagonism was not solely limited to the human C3aR; SB 290157 also
      inhibited C3a-induced Ca(2+) mobilization of RBL-2H3 cells expressing the mouse
      and guinea pig C3aRS: It potently inhibited C3a-mediated ATP release from guinea
      pig platelets and inhibited C3a-induced potentiation of the contractile response
      to field stimulation of perfused rat caudal artery. Furthermore, in animal
      models, SB 290157, inhibited neutrophil recruitment in a guinea pig LPS-induced
      airway neutrophilia model and decreased paw edema in a rat adjuvant-induced
      arthritis model. This selective antagonist may be useful to define the
      physiological and pathophysiological roles of the C3aR.

PMID- 11342659
TI  - Phosphorylation of the activation loop of gamma p21-activated kinase (gamma-Pak)
      and related kinases (MSTs) in normal and stressed neutrophils.
AB  - Neutrophils stimulated with a variety of chemoattractants exhibit a rapid
      activation of two p21-activated kinases (Paks) with molecular masses of
      approximately 63 and 69 kDa (gamma- and alpha-Pak). A number of in vitro studies
      suggest that modification of Thr(402) in the activation loop (AL) of gamma-Pak
      can play a critical role in the regulation of this kinase under certain
      circumstances. A phosphospecific Ab was generated to this region of Pak
      (pPak(AL)Ab). This Ab reacted with activated gamma- and alpha-Pak from fMLP
      stimulated neutrophils that contain the sequence KRXT(P)XXGTP in their ALS: The
      rapid but transient activation of Paks in normal stimulated neutrophils coincided
      with phosphorylation and dephosphorylation at the ALs of these enzymes. In
      contrast, stressed cells exhibited a prolonged phosphorylation at Thr(402) in
      both intact gamma-Pak and a proteolytic fragment of this kinase. The pPak(AL)Ab
      also reacted with the mammalian sterile twenty-like kinases (MSTs) (members of
      the Pak family) in osmotically stressed neutrophils and neutrophils treated with
      certain apoptotic agents (i.e., tumor promoters that inhibit type 1 and 2A
      protein phosphatases) but not in normal fMLP-stimulated cells. Thus, our results
      indicate that the AL of gamma-Pak undergoes transient phosphorylation during
      normal neutrophil stimulation and chronic phosphorylation in stressed cells. In
      addition, we demonstrate that a number of MSTs are present in neutrophils and
      also undergo phosphorylation during stressful circumstances.

PMID- 11342660
TI  - Il-10 up-regulates macrophage expression of the S100 protein S100A8.
AB  - The murine calcium binding protein S100A8 (A8) is a leukocyte chemoattractant,
      but high levels may be protective and scavenge hypochlorite. A8 is induced by
      LPS, IFN-gamma, and TNF in elicited macrophages. Th2 cytokines generally suppress
      proinflammatory gene expression, and IL-4 and IL-13 partially decreased A8
      induction in macrophages and endothelial cells stimulated by LPS or IFN. In
      contrast, IL-10 synergized with LPS and IFN to increase mRNA levels > or =9-fold
      and secreted A8 levels approximately 4-fold. IL-10 decreased the optimal time of
      mRNA expression induced by LPS from 24 to 8 h. Blocking experiments indicated
      that endogenous IL-10 contributes to gene induction by LPS. Cooperation between
      IL-10 and LPS was not due to altered mRNA stability but was dependent on de novo
      protein synthesis. Transfection analysis with A8 luciferase constructs confirmed
      that synergy was due to increased transcription. The region of the promoter
      involved was localized to a 178-bp fragment flanking the transcription start site
      of the gene. This region was also responsible for the suppressive effects of IL-4
      and IL-13. Forskolin, CTP-cAMP, and PGE(2) also enhanced LPS- and IFN-induced A8
      mRNA, whereas indomethacin significantly reduced synergy between IL-10 and LPS.
      Mitogen-activated protein kinase/cyclooxygenase 2/cAMP pathways involving CCAAT
      enhancing binding protein, located within the active promoter, may mediate A8
      gene up-regulation in a manner mechanistically distinct to genes regulated by IL
      10 via the STAT pathway. A8 exhibits pleiotropic effects, and the high levels
      secreted as a result of IL-10 synergy may regulate untoward inflammatory damage
      by virtue of its an antioxidant capacity.

PMID- 11342661
TI  - Mycobacterium bovis strain bacillus Calmette-Guerin-induced liver granulomas
      contain a diverse TCR repertoire, but a monoclonal T cell population is
      sufficient for protective granuloma formation.
AB  - Granuloma formation is a form of delayed-type hypersensitivity requiring CD4(+) T
      cells. Granulomas control the growth and dissemination of pathogens, preventing
      host inflammation from harming surrounding tissues. Using a murine model of
      Mycobacterium bovis strain bacillus Calmette-Guerin (BCG) infection we studied
      the extent of T cell heterogeneity present in liver granulomas. We demonstrate
      that the TCR repertoire of granuloma-infiltrating T cells is very diverse even at
      the single-granuloma level, suggesting that before granuloma closure, a large
      number of different T cells are recruited to the lesion. At the same time, the
      TCR repertoire is selected, because AND TCR transgenic T cells (Valpha11/Vbeta3
      anti-pigeon cytochrome c) are preferentially excluded from granulomas of BCG
      infected AND mice, and cells expressing secondary endemic Vbeta-chains are
      enriched among AND cells homing to granulomas. Next, we addressed whether TCR
      heterogeneity is required for effective granuloma formation. We infected
      5CC7/recombinase-activating gene 2(-/-) mice with recombinant BCG that express
      pigeon cytochrome c peptide in a mycobacterial 19-kDa bacterial surface
      lipoprotein. A CD4(+) T cell with a single specificity in the absence of CD8(+) T
      cells is sufficient to form granulomas and adequately control bacteria. Our study
      shows that expanded monoclonal T cell populations can be protective in
      mycobacterial infection.

PMID- 11342662
TI  - Surfactant protein A suppresses lipopolysaccharide-induced IL-10 production by
      murine macrophages.
AB  - Upon LPS exposure, mononuclear phagocytes produce TNF-alpha and IL-10, two
      cytokines with pro- and anti-inflammatory activities, respectively. We previously
      described that murine resident alveolar macrophages, which play a central role in
      the immunosurveillance of the lung alveoli, do not synthesize IL-10 in vivo or in
      vitro when exposed to LPS. In the present report we demonstrate that during lung
      inflammation induced by the intranasal administration of LPS, bronchoalveolar
      cells collected between days 3 and 5 are able to synthesize IL-10 when exposed to
      LPS. We also show that depletion of resident alveolar macrophages by an
      intratracheal instillation of liposome-encapsulated clodronate is followed by
      subsequent replenishment of the airspaces by mononuclear phagocytes. This is
      accompanied by the transient competence of cells for IL-10 production. The cell
      capacity to produce IL-10 is evident up to 3 days and then decreases. This led us
      to hypothesize that the alveolar environment contains a down-regulator of LPS
      induced IL-10 synthesis by recently emigrating mononuclear phagocytes. We show
      that the surfactant protein A, an airspace protein that has known
      immunomodulatory activities, dramatically inhibits LPS-induced IL-10 formation by
      bone marrow-derived macrophages. These data show a difference between resident
      and inflammatory macrophages with respect to IL-10 synthesis. Moreover, this
      study highlights for the first time the inhibitory role of surfactant protein A
      in the anti-inflammatory activity of macrophages through inhibition of IL-10
      production.

PMID- 11342663
TI  - ATP mediates calcium signaling between astrocytes and microglial cells:
      modulation by IFN-gamma.
AB  - Calcium-mediated intercellular communication is a mechanism by which astrocytes
      communicate with each other and modulate the activity of adjacent cells,
      including neurons and oligodendrocytes. We have investigated whether microglia,
      the immune effector cells involved in several diseases of the CNS, are actively
      involved in this communication network. To address this issue, we analyzed
      calcium dynamics in fura-2-loaded cocultures of astrocytes and microglia under
      physiological conditions and in the presence of the inflammatory cytokine IFN
      gamma. The intracellular calcium increases in astrocytes, occurring spontaneously
      or as a result of mechanical or bradykinin stimulation, induced the release of
      ATP, which, in turn, was responsible for triggering a delayed calcium response in
      microglial cells. Repeated stimulations of microglial cells by astrocyte-released
      ATP activated P2X(7) purinergic receptor on microglial cells and greatly
      increased membrane permeability, eventually leading to microglial apoptosis. IFN
      gamma increased ATP release and potentiated the P2X(7)-mediated cytolytic effect.
      This is the first study showing that ATP mediates a form of calcium signaling
      between astrocytes and microglia. This mechanism of intercellular communication
      may be involved in controlling the number and function of microglial cells under
      pathophysiologic CNS conditions.

PMID- 11342664
TI  - Il-18 gene transfer by adenovirus prevents the development of and reverses
      established allergen-induced airway hyperreactivity.
AB  - We examined the role of IL-18 in preventing the development of and in reversing
      established allergen-induced airway inflammation and airway hyperreactivity
      (AHR), the cardinal features of asthma. IL-18, which potently induces IFN-gamma,
      was administered into the respiratory tract as cDNA in a replication-deficient
      adenovirus (Adv). Treatment of OVA-sensitized mice with the IL-18-expressing Adv
      reduced allergen-specific IL-4 production, airway eosinophilia, and mucus
      production, increased IFN-gamma production, and prevented the development of AHR.
      The effects of the IL-18 Adv treatment were dependent on the presence of IFN
      gamma and IL-12. Moreover, administration of the IL-18 Adv to mice with
      established AHR greatly reduced AHR and IL-4 production and increased IFN-gamma
      production. These results demonstrate that IL-18, when administered by Adv into
      the respiratory tract, effectively reduces AHR and replaces an established Th2
      biased immune response with a Th1-biased response.

PMID- 11342665
TI  - Apoptosis: one of the mechanisms that maintains unresponsiveness of the
      intestinal mucosal immune system.
AB  - Intestinal mucosa is constantly exposed to environmental AGS: Activation of
      lamina propria (LP) T cells by luminal Ags may lead to the production of
      inflammatory cytokines and subsequent mucosal inflammation and tissue damage.
      However, in normal circumstances, LP T cells do not respond to antigenic
      stimulation. The mechanisms of this unresponsiveness in healthy subjects are not
      fully understood. In this study, we found by in vivo analysis that, except for T
      cells in lymph nodules of the mucosa, 15% of LP T cells underwent apoptosis in
      normal individuals. In contrast, there was a marked reduction in apoptosis of LP
      T cells in patients with inflammatory bowel disease (Crohn's disease and
      ulcerative colitis) and those with specific colitis. Our findings suggest that
      apoptosis might be a mechanism that turns off mucosal T cell responses to
      environmental Ags in healthy subjects, and resistance to apoptosis could be an
      important cause of mucosal immune dysregulation and tissue inflammation in
      colitis.

PMID- 11342666
TI  - A novel serum protein that is selectively produced by cytotoxic lymphocytes.
AB  - Cytotoxic lymphocytes such as CTL and NK cells play principal roles in the host
      defense mechanisms. Monitoring these effector cells in vivo is helpful to
      understand the immune responses in disorders such as cancer and infectious
      diseases. In this study, we identified a novel secretory protein, killer-specific
      secretory protein of 37 kDa (Ksp37), as a Th1-specific protein by a subtractive
      cloning method between human Th1 and Th2 cells. In peripheral blood leukocytes,
      Ksp37 expression was limited to Th1-type CD4(+) T cells, effector CD8(+) T cells,
      gammadelta T cells, and CD16(+) NK cells. Most of these Ksp37-expressing cells
      coexpressed perforin, indicating that Ksp37 is selectively and commonly expressed
      in the lymphocytes that have cytotoxic potential. Ksp37 was released at constant
      rate from both unstimulated and stimulated PBMCs in vitro and also detected in
      normal human sera. In healthy individuals, serum Ksp37 levels were significantly
      higher in children (mean +/- SD; 984 +/- 365 ng/ml for age 0-9) than in adults
      (441 +/- 135 ng/ml for age 20-99), consistent with reported differences in the
      absolute counts of blood T and NK cells between children and adults. In patients
      with infectious mononucleosis, transient elevation of serum Ksp37 levels was
      observed during the early acute phase of primary EBV infection. These results
      suggest that Ksp37 may be involved in an essential process of cytotoxic
      lymphocyte-mediated immunity and that Ksp37 may also have clinical value as a new
      type of serum indicator for monitoring cytotoxic lymphocytes in vivo.

PMID- 11342667
TI  - Genetic regulation of autoimmune disease: BALB/c background TGF-beta 1-deficient
      mice develop necroinflammatory IFN-gamma-dependent hepatitis.
AB  - Autoimmune hepatitis (AIH) in humans arises spontaneously in genetically
      susceptible individuals and is associated with the presence of Th1 cells in the
      liver. The understanding of AIH has advanced more slowly than that of other organ
      specific autoimmune diseases, however, largely because of the lack of an
      appropriate animal model. We now describe a new mouse model characterized by
      spontaneous development of necroinflammatory hepatitis that is restricted by
      genetic background. Mice deficient in the immunomodulatory cytokine TGF-beta1
      were extensively back-bred to the BALB/c background. The BALB/c background
      dramatically modified the phenotype of TGF-beta1(-/-) mice: specifically, BALB/c
      TGF-beta1(-/-) mice developed a lethal necroinflammatory hepatitis that was not
      observed in TGF-beta1(-/-) mice on a different genetic background. BALB/c
      background TGF-beta1(-/-) livers contained large numbers of activated CD4(+) T
      cells that produced large quantities of IFN-gamma, but little IL-4, identifying
      them as Th1 cells. BALB/c background TGF-beta1(-/-)/IFN-gamma(-/-) double
      knockout mice, generated by cross-breeding, did not develop necroinflammatory
      hepatitis, demonstrating that IFN-gamma is mechanistically required for its
      pathogenesis. This represents the first murine model of hepatitis that develops
      spontaneously, is restricted by genetic background, and is dependent upon the Th1
      cytokine IFN-gamma, and that thus recapitulates these important aspects of AIH.

PMID- 11342668
TI  - Calreticulin, a potential cell surface receptor involved in cell penetration of
      anti-DNA antibodies.
AB  - A 50-kDa protein was purified as a potential receptor, using an affinity matrix
      containing biotinylated F14.6 or H9.3 anti-DNA mAbs derived from autoimmune (New
      Zealand Black x New Zealand White)F(1) mouse and membrane extracts from cells.
      This protein was identified as calreticulin (CRT) by microsequencing. Confocal
      microscopy and FACS analysis showed that CRT was present on the surface of
      various cells. CRT protein was recognized by a panel of anti-DNA mAbs in ELISA.
      The binding of F14.6 to lymphocytes and Chinese hamster ovary cells was inhibited
      by soluble CRT or SPA-600. Thus, the anti-DNA mAbs used in this study bound to
      CRT, suggesting that CRT may mediate their penetration into the cells and play an
      important role in lupus pathogenesis.

PMID- 11342669
TI  - Anti-CTLA-4 antibody treatment triggers determinant spreading and enhances murine
      myasthenia gravis.
AB  - CTLA-4 appears to be a negative regulator of T cell activation and is implicated
      in T cell-mediated autoimmune diseases. Experimental autoimmune myasthenia gravis
      (EAMG), induced by immunization of C57BL/6 mice with acetylcholine receptor
      (AChR) in adjuvant, is an autoantibody-mediated disease model for human
      myasthenia gravis (MG). The production of anti-AChR Abs in MG and EAMG is T cell
      dependent. In the present study, we demonstrate that anti-CTLA-4 Ab treatment
      enhances T cell responses to AChR, increases anti-AChR Ab production, and
      provokes a rapid onset and severe EAMG. To address possible mechanisms underlying
      the enhanced autoreactive T cell responses after anti-CTLA-4 Ab treatment, mice
      were immunized with the immunodominant peptide alpha(146-162) representing an
      extracellular sequence of the ACHR: Anti-CTLA-4 Ab, but not control Ab, treatment
      subsequent to peptide immunization results in clinical EAMG with diversification
      of the autoantibody repertoire as well as enhanced T cell proliferation against
      not only the immunizing alpha(146-162) peptide, but also against other
      subdominant epitopes. Thus, treatment with anti-CTLA-4 Ab appears to induce
      determinant spreading, diversify the autoantibody repertoire, and enhance B cell
      mediated autoimmune disease in this murine model of MG.

PMID- 11342670
TI  - Nonproliferating bystander CD4+ T cells lacking activation markers support HIV
      replication during immune activation.
AB  - HIV replicates primarily in lymphoid tissue and immune activation is a major
      stimulus in vivo. To determine the cells responsible for HIV replication during
      Ag-driven T cell activation, we used a novel in vitro model employing dendritic
      cell presentation of superantigen to CD4(+) T cells. Dendritic cells and CD4(+) T
      cells are the major constituents of the paracortical region of lymphoid organs,
      the main site of Ag-specific activation and HIV replication. Unexpectedly,
      replication occurred in nonproliferating bystander CD4(+) T cells that lacked
      activation markers. In contrast, activated Ag-specific cells were relatively
      protected from infection, which was associated with CCR5 and CXC chemokine
      receptor 4 down-regulation. The finding that HIV replication is not restricted to
      highly activated Ag-specific CD4(+) T cells has implications for therapy, efforts
      to eradicate viral reservoirs, immune control of HIV, and Ag-specific immune
      defects.

PMID- 11342671
TI  - Complement component C3 is not required for full expression of immune complex
      glomerulonephritis in MRL/lpr mice.
AB  - Complement activation and tissue deposition of complement fragments occur during
      disease progression in lupus nephritis. Genetic deficiency of some complement
      components (e.g., Factor B) and infusion of complement inhibitors (e.g., Crry,
      anti-C5 Ab) protect against inflammatory renal disease. Paradoxically, genetic
      deficiencies of early components of the classical complement pathway (e.g., C1q,
      C4, and C2) are associated with an increased incidence of lupus in humans and
      lupus-like disease in murine knockout strains. Complement protein C3 is the
      converging point for activation of all three complement pathways and thus plays a
      critical role in biologic processes mediated by complement activation. To define
      the role of C3 in lupus nephritis, mice rendered C3 deficient by targeted
      deletion were backcrossed for eight generations to MRL/lpr mice, a mouse strain
      that spontaneously develops lupus-like disease. We derived homozygous knockout
      (C3(-/-)), heterozygous (C3(+/-)), and C3 wild-type (C3(+/+)) MRL/lpr mice. Serum
      levels of autoantibodies and circulating immune complexes were similar among the
      three groups. However, there was earlier and significantly greater albuminuria in
      the C3(-/-) mice compared with the other two groups. Glomerular IgG deposition
      was also significantly greater in the C3(-/-) mice than in the other two groups,
      although overall pathologic renal scores were similar. These results indicate
      that C3 and/or activation of C3 is not required for full expression of immune
      complex renal disease in MRL/lpr mice and may in fact play a beneficial role via
      clearance of immune complexes.

PMID- 11342672
TI  - Impairment of CD8+ T suppressor cell function in patients with active systemic
      lupus erythematosus.
AB  - Alteration of T cell suppression function has been recognized in patients with
      systemic lupus erythematosus (SLE). Recently, CD8(+) T suppressor lymphocytes
      (CD8(+) Ts) have been generated in vitro by incubating purified CD8(+) T cells
      with IL-2 and GM-CSF. Using this method, we generated CD8(+) Ts from patients
      affected by SLE. No major differences were found in the CD8(+) Ts phenotype
      between SLE patients and healthy subjects. CD8(+) Ts from SLE patients with
      active disease did not inhibit the anti-CD3 mAb-induced proliferation of
      autologous PBMC, whereas CD8(+) Ts from SLE patients in remission exerted an
      inhibitory activity comparable to normal subjects. The inhibitory effect of
      CD8(+) Ts cells was neither mediated by cytotoxic activity nor by apoptosis
      induction. Two cytokines, IFN-gamma and IL-6, were found to be responsible for
      the function of CD8(+) TS: In fact, counteraction of CD8(+) Ts suppression
      activity was obtained by blocking IFN-gamma with a specific Ab or by inhibiting
      CD8(+) Ts-mediated IL-6 secretion by an antisense oligonucleotide. Interestingly,
      CD8(+) Ts from SLE patients showed a peculiar cytokine pattern characterized by
      an impaired secretion of IL-6 and an increased secretion of IL-12. Thus, it
      appears that an altered balance between inhibitory (IL-6) and stimulatory (IL-12)
      cytokines might be responsible for the functional impairment of CD8(+) Ts in SLE
      patients.

PMID- 11342673
TI  - Chlamydia pneumoniae and its proposed link to multiple sclerosis: to be or not to
      be?

PMID- 11342674
TI  - Association of Chlamydia pneumoniae and multiple sclerosis: stage two?

PMID- 11342675
TI  - Chlamydia: conflict and controversy.

PMID- 11342676
TI  - Of MCI and dementia: improving diagnosis and treatment.

PMID- 11342677
TI  - Practice parameter: early detection of dementia: mild cognitive impairment (an
      evidence-based review). Report of the Quality Standards Subcommittee of the
      American Academy of Neurology.
AB  - OBJECTIVE: The goal of this project was to determine whether screening different
      groups of elderly individuals in a general or specialty practice would be
      beneficial in detecting dementia. BACKGROUND: Epidemiologic studies of aging and
      dementia have demonstrated that the use of research criteria for the
      classification of dementia has yielded three groups of subjects: those who are
      demented, those who are not demented, and a third group of individuals who cannot
      be classified as normal or demented but who are cognitively (usually memory)
      impaired. METHODS: The authors conducted computerized literature searches and
      generated a set of abstracts based on text and index words selected to reflect
      the key issues to be addressed. Articles were abstracted to determine whether
      there were sufficient data to recommend the screening of asymptomatic
      individuals. Other research studies were evaluated to determine whether there was
      value in identifying individuals who were memory-impaired beyond what one would
      expect for age but who were not demented. Finally, screening instruments and
      evaluation techniques for the identification of cognitive impairment were
      reviewed. RESULTS: There were insufficient data to make any recommendations
      regarding cognitive screening of asymptomatic individuals. Persons with memory
      impairment who were not demented were characterized in the literature as having
      mild cognitive impairment. These subjects were at increased risk for developing
      dementia or AD when compared with similarly aged individuals in the general
      population. RECOMMENDATIONS: There were sufficient data to recommend the
      evaluation and clinical monitoring of persons with mild cognitive impairment due
      to their increased risk for developing dementia (Guideline). Screening
      instruments, e.g., Mini-Mental State Examination, were found to be useful to the
      clinician for assessing the degree of cognitive impairment (Guideline), as were
      neuropsychologic batteries (Guideline), brief focused cognitive instruments
      (Option), and certain structured informant interviews (Option). Increasing
      attention is being paid to persons with mild cognitive impairment for whom
      treatment options are being evaluated that may alter the rate of progression to
      dementia.

PMID- 11342678
TI  - Practice parameter: diagnosis of dementia (an evidence-based review). Report of
      the Quality Standards Subcommittee of the American Academy of Neurology.
AB  - OBJECTIVE: To update the 1994 practice parameter for the diagnosis of dementia in
      the elderly. BACKGROUND: The AAN previously published a practice parameter on
      dementia in 1994. New research and clinical developments warrant an update of
      some aspects of diagnosis. METHODS: Studies published in English from 1985
      through 1999 were identified that addressed four questions: 1) Are the current
      criteria for the diagnosis of dementia reliable? 2) Are the current diagnostic
      criteria able to establish a diagnosis for the prevalent dementias in the
      elderly? 3) Do laboratory tests improve the accuracy of the clinical diagnosis of
      dementing illness? 4) What comorbidities should be evaluated in elderly patients
      undergoing an initial assessment for dementia? RECOMMENDATIONS: Based on evidence
      in the literature, the following recommendations are made. 1) The DSM-III-R
      definition of dementia is reliable and should be used (Guideline). 2) The
      National Institute of Neurologic, Communicative Disorders and Stroke--AD and
      Related Disorders Association (NINCDS-ADRDA) or the Diagnostic and Statistical
      Manual, 3rd edition, revised (DSM-IIIR) diagnostic criteria for AD and clinical
      criteria for Creutzfeldt--Jakob disease (CJD) have sufficient reliability and
      validity and should be used (Guideline). Diagnostic criteria for vascular
      dementia, dementia with Lewy bodies, and frontotemporal dementia may be of use in
      clinical practice (Option) but have imperfect reliability and validity. 3)
      Structural neuroimaging with either a noncontrast CT or MR scan in the initial
      evaluation of patients with dementia is appropriate. Because of insufficient data
      on validity, no other imaging procedure is recommended (Guideline). There are
      currently no genetic markers recommended for routine diagnostic purposes
      (Guideline). The CSF 14-3-3 protein is useful for confirming or rejecting the
      diagnosis of CJD (Guideline). 4) Screening for depression, B(12) deficiency, and
      hypothyroidism should be performed (Guideline). Screening for syphilis in
      patients with dementia is not justified unless clinical suspicion for
      neurosyphilis is present (Guideline). CONCLUSIONS: Diagnostic criteria for
      dementia have improved since the 1994 practice parameter. Further research is
      needed to improve clinical definitions of dementia and its subtypes, as well as
      to determine the utility of various instruments of neuroimaging, biomarkers, and
      genetic testing in increasing diagnostic accuracy.

PMID- 11342679
TI  - Practice parameter: management of dementia (an evidence-based review). Report of
      the Quality Standards Subcommittee of the American Academy of Neurology.
AB  - OBJECTIVE: To define and investigate key issues in the management of dementia and
      to make literature-based treatment recommendations. METHODS: The authors searched
      the literature for four clinical questions: 1) Does pharmacotherapy for cognitive
      symptoms improve outcomes in patients with dementia? 2) Does pharmacotherapy for
      noncognitive symptoms improve outcomes in patients with dementia? 3) Do
      educational interventions improve outcomes in patients and/or caregivers? 4) Do
      other nonpharmacologic interventions improve outcomes in patients and/or
      caregivers? RESULTS: Cholinesterase inhibitors benefit patients with AD
      (Standard), although the average benefit appears small; vitamin E likely delays
      the time to clinical worsening (Guideline); selegiline, other antioxidants, anti
      inflammatories, and estrogen require further study. Antipsychotics are effective
      for agitation or psychosis in patients with dementia where environmental
      manipulation fails (Standard), and antidepressants are effective in depressed
      patients with dementia (Guideline). Educational programs should be offered to
      family caregivers to improve caregiver satisfaction and to delay the time to
      nursing home placement (Guideline). Staff of long-term care facilities should
      also be educated about AD to minimize the unnecessary use of antipsychotic
      medications (Guideline). Behavior modification, scheduled toileting, and prompted
      voiding reduce urinary incontinence (Standard). Functional independence can be
      increased by graded assistance, skills practice, and positive reinforcement
      (Guideline).

PMID- 11342681
TI  - CSF oligoclonal bands in MS include antibodies against Chlamydophila antigens.
AB  - BACKGROUND: Considerable evidence suggests the role of an infectious agent in MS.
      The presence of Chlamydophila pneumoniae in CSF from patients with MS was shown
      earlier; to further examine this association the reactivity of the oligoclonal
      antibody response in the CSF of patients with MS to C pneumoniae antigens was
      determined and compared with other antigens. METHODS: Seventeen patients with MS
      and 14 control subjects with other neurologic disease were studied. Affinity
      driven immunoblot studies and solid-phase adsorption of CSF oligoclonal bands by
      elementary body antigens of C pneumoniae, viral antigens (measles and herpes
      simplex virus-1), bacterial antigen (Escherichia coli and Staphylococcus aureus),
      and heat shock protein-60 were performed. RESULTS: Affinity-driven immunoblot
      studies demonstrated reactivity of oligoclonal bands in CSF samples from 16
      patients with MS against elementary body antigens of C pneumoniae. None of the
      control subjects showed a prominent reactivity to elementary body antigens of C
      pneumoniae. In 14 of 17 patients with MS examined, oligoclonal bands were
      adsorbed either partially or completely from the CSF by elementary body antigens
      of C pneumoniae, but not by myelin basic protein, heat shock protein-60, or
      bacterial or viral antigens. In three patients with subacute sclerosing
      panencephalitis, adsorption of oligoclonal bands was seen with measles virus
      antigens but not with elementary body antigens of C pneumoniae. CONCLUSIONS:
      Oligoclonal bands in CSF of patients with MS include antibodies against
      Chlamydophila antigens.

PMID- 11342682
TI  - Differential cognitive and behavioral effects of carbamazepine and lamotrigine.
AB  - BACKGROUND: The relative cognitive and behavioral effects of lamotrigine compared
      with the older standard antiepileptic drugs (AED) are uncertain. OBJECTIVE: To
      directly compare the cognitive and behavioral effects of carbamazepine and
      lamotrigine. METHODS: The cognitive and behavioral effects of carbamazepine and
      lamotrigine were assessed in 25 healthy adults using a double-blind, randomized
      crossover design with two 10-week treatment periods. During each treatment
      condition, subjects received either lamotrigine (150 mg/day) or carbamazepine
      (mean 696 mg/day) adjusted to a dose to achieve midrange standard therapeutic
      blood levels (mean 7.6 microg/mL). Subjects were tested at the end of each AED
      treatment period and in three drug-free conditions (two pretreatment baselines
      and a final posttreatment period [1 month after last AED]). The
      neuropsychological test battery included 19 measures yielding 40 total variables.
      RESULTS: Direct comparison of the two AED revealed significantly better
      performance on 19 (48%) variables for lamotrigine but none for carbamazepine.
      Differences spanned both objective cognitive and subjective behavioral measures,
      including cognitive speed, memory, graphomotor coding, neurotoxic symptoms, mood
      factors, sedation, perception of cognitive performance, and other quality-of-life
      perceptions. Comparison of carbamazepine with the nondrug average revealed
      significantly better performance for nondrug average on 24 (62%) variables but
      none for carbamazepine. Comparison of lamotrigine with nondrug average revealed
      better performance on one (2.5%) variable for nondrug average and on one (2.5%)
      variable for lamotrigine. CONCLUSION: Lamotrigine produces significantly fewer
      untoward cognitive and behavioral effects than carbamazepine at the dosages used
      in this study.

PMID- 11342683
TI  - VLDL receptor polymorphism, cognitive impairment, and dementia.
AB  - OBJECTIVE: Clinical, epidemiologic, and pathologic observations suggest that
      vascular risk factors are associated with impaired cognition. Previous studies
      supported an association between cognitive decline and APOE. Although the
      underlying mechanism is not clear, it might involve apoE receptors, such as the
      very low density lipoprotein receptor. METHODS: The impact of a polymorphic
      triplet repeat in the very low density lipoprotein receptor gene (VLDLR) on
      cognitive function was examined in two independent studies: a population study
      involving 221 demented subjects compared with 249 control subjects and a clinical
      study involving 124 demented subjects compared with 179 control subjects.
      RESULTS: In the population study, the presence of the VLDLR-5-repeat allele was
      associated with a relative risk of dementia (OR, 1.9; 95% CI, 1.2 to 3.0). This
      result was confirmed in the clinical study (OR, 8.1; 95% CI, 4.4 to 15.1) and was
      more pronounced in subjects with mixed or vascular dementia than in patients with
      AD. CONCLUSION: The VLDLR-5-repeat allele may constitute a genetic susceptibility
      factor for dementia, particularly in the presence of vascular risk factors. This
      observation suggests the influence of vascular risk factors in the occurrence of
      dementia.

PMID- 11342684
TI  - Vitamin B(12) and folate in relation to the development of Alzheimer's disease.
AB  - OBJECTIVE: To explore the associations of low serum levels of vitamin B(12) and
      folate with AD occurrence. METHODS: A population-based longitudinal study in
      Sweden, the Kungsholmen PROJECT: A random sample of 370 nondemented persons, aged
      75 years and older and not treated with B(12) and folate, was followed for 3
      years to detect incident AD cases. Two cut-off points were used to define low
      levels of vitamin B(12) (< or =150 and < or =250 pmol/L) and folate (< or =10 and
      < or =12 nmol/L), and all analyses were performed using both definitions. AD and
      other types of dementia were diagnosed by specialists according to DSM-III-R
      criteria. RESULTS: When using B(12) < or =150 pmol/L and folate < or =10 nmol/L
      to define low levels, compared with people with normal levels of both vitamins,
      subjects with low levels of B(12) or folate had twice higher risks of developing
      AD (relative risk [RR] = 2.1, 95% CI = 1.2 to 3.5). These associations were even
      stronger in subjects with good baseline cognition (RR = 3.1, 95% CI = 1.1 to
      8.4). Similar relative risks of AD were found in subjects with low levels of
      B(12) or folate and among those with both vitamins at low levels. A comparable
      pattern was detected when low vitamin levels were defined as B(12) < or =250
      pmol/L and folate < or =12 nmol/L. CONCLUSIONS: This study suggests that vitamin
      B(12) and folate may be involved in the development of AD. A clear association
      was detected only when both vitamins were taken into account, especially among
      the cognitively intact subjects. No interaction was found between the two
      vitamins. Monitoring serum B(12) and folate concentration in the elderly may be
      relevant for prevention of AD.

PMID- 11342685
TI  - A comparison of (18)F-dopa PET and inversion recovery MRI in the diagnosis of
      Parkinson's disease.
AB  - OBJECTIVE: To quantify structural changes in the substantia nigra of patients
      with PD with inversion recovery MRI and to compare these with striatal
      dopaminergic function measured with (18)F-dopa PET. METHODS: The authors studied
      10 patients with PD and eight age-matched control subjects with a combination of
      MR sequences previously reported to be sensitive to nigral cell loss. Striatal
      regions of interest were defined on T1-weighted MRI coregistered to (18)F-dopa
      PET in all subjects. RESULTS: Discriminant function analysis of the quantified MR
      nigral signal correctly classified 83% of the combined PD patient/control group;
      three of 10 PD cases were incorrectly classified as "normal" (Wilks' lambda =
      0.724, p > 0.05). Discriminant function analysis correctly classified 100% of PD
      patients and control subjects with (18)F-dopa PET based on mean caudate and
      putamen K(i) values (Wilks' lambda = 0.065, p < 0.001). Correlations between mean
      putamen K(i) and rostral and caudal nigral MR signal changes and mean caudate
      K(i) and caudal nigral MR signal changes were found (r = -0.76, -0.69, -0.80, p <
      0.05). CONCLUSION: (18)F-dopa PET is more reliable than inversion recovery MRI in
      discriminating patients with moderately severe PD from normal subjects. However,
      the structural changes detected within the substantia nigra of patients with PD
      found using inversion recovery MRI correlate with measures of striatal
      dopaminergic function using (18)F-dopa PET.

PMID- 11342686
TI  - FLAIR MRI of striatonigral degeneration.

PMID- 11342687
TI  - Samuel Adams' tremor.
AB  - BACKGROUND: Samuel Adams (1722--1803), the American Revolutionist and brewer, is
      said to have had a tremor. There has not been a formal study of the clinical
      characteristics and progression of his tremor. OBJECTIVE: To use historical
      accounts and original materials to document the clinical characteristics and
      progression of Adams' tremor. MATERIALS: In addition to historical accounts of
      Adams, the following materials were reviewed: 1) Samuel Adams' known writings,
      including personal and political letters, published posthumously in a four-volume
      book; and 2) original letters and speeches (handwritten by Adams) that are held
      in collection in the Manuscripts and Archives Division of the New York Public
      Library. RESULTS: Adams had a tremor that affected his hands, head, and voice.
      Although mild, the tremor was already manifest when Adams was in his early 40s.
      Adams, who was very prolific, experienced progressive difficulty with his ability
      to write while in his 50s and early 60s. His letters contain frequent references
      to his illness and reveal a penmanship that became more compromised with time. By
      age 71, he was forced to dictate all his correspondence. His tremor was familial,
      affecting his daughter Hannah and her children. CONCLUSIONS: Samuel Adams'
      progressive tremor rendered him unable to write his own letters for the last 10
      years of his life. Adams had one of the earliest documented cases of essential
      tremor.

PMID- 11342688
TI  - Neurologists' use of ICD-9CM codes for dementia.
AB  - Neurologists' use of ICD-9CM codes in a sample of 181 consecutive, new patients
      evaluated for dementia by 48 of all 49 neurologists from the Rochester, NY, area
      over a 1-year period was examined. The specific code for AD, 331.0, was used for
      only 36.5% of patients judged by the neurologist to have AD as the most likely
      diagnosis. Other codes used were not inaccurate but would result in lower
      reimbursement. Variation in coding could affect validity of dementia research
      using claims data.

PMID- 11342689
TI  - A pilot study of drug-induced hypertension for treatment of acute stroke.
AB  - The aim of this pilot study was to determine whether the use of induced
      hypertension in acute stroke is feasible and associated with neurologic
      improvement. Phenylephrine was used to raise the systolic blood pressure in
      patients with acute stroke by 20%, not to exceed 200 mmHG: Of 13 patients
      treated, 7 improved by 2 points on the NIH Stroke SCALE: No systemic or
      neurologic complications were seen. The authors conclude that induced
      hypertension in acute stroke is feasible and likely safe and can improve the
      neurologic examination in some patients.

PMID- 11342690
TI  - A major locus for several phenotypes of myoclonus--dystonia on chromosome 7q.
AB  - Myoclonus--dystonia is a genetically heterogeneous autosomal dominant disorder
      caused by a mutation in the D2 dopamine receptor on chromosome 11 and a locus on
      chromosome 7q21-q31. The authors tested linkage to the chromosome 7q candidate
      region in four families with either myoclonic dystonia (n = 3) or essential
      myoclonus (n = 1). Age at onset ranged from 0.5 to 38 years. Only four patients
      from two families had a positive response to alcohol. Lod scores were positive in
      all four families, suggesting that chromosome 7q21-q31 is a major locus for
      myoclonus-dystonia with several phenotypes.

PMID- 11342691
TI  - Proliferation index is related to patient age in glioblastoma.
AB  - Younger patients with glioblastomas have a significantly better prognosis than do
      older patients. To determine whether patient age might be related to
      proliferation of glioblastoma cells, glioblastomas from patients of different
      ages were stained with the Molecular Immunology Borstel number 1 antibody to
      detect proliferating cells. Younger patient age was a significant predictor of a
      low Molecular Immunology Borstel number 1 proliferation index (p = 0.0001). This
      previously unreported association favors an intrinsic difference in the type of
      glioblastomas that afflict younger patients.

PMID- 11342692
TI  - Response of radiochemotherapy-associated cerebral edema to a phytotherapeutic
      agent, H15.
AB  - Twelve patients with brain tumors and progressive edema caused by tumor
      progression or radiochemotherapy-related leukoencephalopathy were treated with
      H15, a phytotherapeutic anti-inflammatory agent. Edema was reduced in two of
      seven patients with glioblastoma with tumor progression and in three of five
      patients with treatment-related leukoencephalopathy. All patients with
      leukoencephalopathy improved clinically for several months.

PMID- 11342693
TI  - Monocular elevator paresis in neurofibromatosis type 2.
AB  - A retrospective review of 29 consecutive unselected patients referred for neuro
      ophthalmic evaluation after the diagnosis of neurofibromatosis type 2 (NF2)
      showed that four of them had a monocular elevator paresis. In two of the four MRI
      demonstrated lesions, presumed to be schwannomas, of the third nerve. These
      findings indicate that monocular elevator paresis is a common neuro-ophthalmic
      finding in NF2, which the authors suspect is probably a sign of third nerve
      infiltration or compression by a schwannoma.

PMID- 11342694
TI  - Differentiation between reactive gliosis and diffuse astrocytoma by in situ
      hybridization.
AB  - The authors examined the use of chromosomal analysis by in situ hybridization to
      differentiate between nonneoplastic reactive gliosis and astrocytomas in cases in
      which routine histology was inconclusive. Numerical chromosomal aberrations were
      found in 80% of low-grade astrocytoma specimens and in none of the reactive
      gliosis specimens. Aneusomic tumor cells were detected in four of 13 stereotactic
      samples with an initially inconclusive tissue diagnosis, three of which were
      later diagnosed as astrocytoma. The in situ hybridization procedure may have
      additional value in the differential diagnosis of reactive gliosis versus low
      grade astrocytoma.

PMID- 11342695
TI  - Guillain-Barre syndrome associated with IgG monospecific to ganglioside GD1b.
AB  - The authors examined serum antiglycolipid antibodies in 445 patients with
      Guillain-Barre syndrome (GBS). Among them, nine had anti-GD1b IgG antibodies with
      no reactivity to other glycolipids tested. All those patients had sensory
      disturbance, and none had the primary axonal form. Anti-GD1b IgG antibodies may
      bind to primary sensory neurons and paranodal myelin, where GD1b is localized,
      and be involved in the pathogenesis of sensory disturbance and demyelination.
      However, more study is needed to substantiate the roles of anti-GD1b IgG
      antibodies.

PMID- 11342696
TI  - SPG15, a new locus for autosomal recessive complicated HSP on chromosome 14q.
AB  - The authors studied two families with autosomal recessive hereditary spastic
      paraplegia (HSP) complicated by the presence of additional symptoms of pigmented
      maculopathy, distal amyotrophy, dysarthria, mental retardation, and further
      intellectual deterioration. Evidence was obtained for linkage to a locus on
      chromosome 14q that is distinct from the SPG3 locus for autosomal dominant HSP
      (D14S77: lod score of 4.20 at zero recombination). Haplotype construction of
      nearby markers confirms the existence of this novel HSP locus (SPG15) and narrows
      it to a 19-cM interval flanked by D14S1038 and D14S61.

PMID- 11342697
TI  - Increased familial risk of cluster headache.
AB  - The authors studied the occurrence of cluster headache in the families of 220
      Italian patients with cluster headache. A positive family history was found in
      20% (44/220) of the families. Compared with the general population, first-degree
      relatives had a 39-fold significantly increased risk of cluster headache. Second
      degree relatives had an eightfold significantly increased risk. The increased
      familial risk strongly supports the hypothesis that cluster headache has a
      genetic component in some families.

PMID- 11342698
TI  - A favorable response to antiparkinsonian treatment in juvenile neuronal ceroid
      lipofuscinosis.
AB  - To study the effect of dopaminergic drugs on the parkinsonism in juvenile
      neuronal ceroid lipofuscinosis, the authors conducted an open study of 21
      patients. According to the motor Unified PD Rating Scale (UPDRS) score, treatment
      was initiated with either levodopa (n = 10) or selegiline (n = 6). Five patients
      served as a control group. The UPDRS score after 1 year was compared with the
      score at onset. Both in the control group and in the selegiline group, the mean
      UPDRS score increased, whereas in the levodopa group, the mean UPDRS score
      decreased. The difference between the levodopa group and the control group was
      significant.

PMID- 11342699
TI  - Dual-release formulation, a novel principle in L-dopa treatment of Parkinson's
      disease.
AB  - A single morning dose of dual-release formulation was compared with a slow
      release formulation of L-dopa plus benserazide in a randomized, double-blind,
      cross-over study in 16 fluctuating patients with PD. The mean time to "on" was
      shorter with the dual-release formulation (43 +/- 31 minutes) than with the slow
      release formulation (81 +/- 39 minutes) (p < 0.001), whereas the mean time to
      relapse to "off" was similar for both formulations. The dual-release formulation
      had a significantly shorter time to reach peak concentration (t(max)) and greater
      maximum concentration (C(max)) and area under the plasma concentration time curve
      (AUC(0--5 h)) than the slow-release formulation, whereas apparent elimination
      half-life (t(1/2)) was similar for both formulations.

PMID- 11342700
TI  - Unusually prominent perivascular spaces.

PMID- 11342701
TI  - Intracranial hemorrhages associated with sumatriptan.

PMID- 11342702
TI  - Brainstem infarction following Korean viper bite.

PMID- 11342703
TI  - Association between the alpha(1a) calcium channel gene CACNA1A and idiopathic
      generalized epilepsy.

PMID- 11342704
TI  - Interaction between ESR1 and HLA-DR2 may contribute to the development of MS in
      women.

PMID- 11342705
TI  - Significance of hyperintense vessels on FLAIR MRI in acute stroke.

PMID- 11342706
TI  - Worsening of motor function in Parkinson's disease: a "typical" response to
      "atypical" antipsychotic medications.

PMID- 11342707
TI  - Complications during apnea testing in the determination of brain death:
      predisposing factors.

PMID- 11342708
TI  - Quality of life as a predictor for change in disability in MS.

PMID- 11342709
TI  - Structural adaptation of enzymes to low temperatures.
AB  - A systematic comparative analysis of 21 psychrophilic enzymes belonging to
      different structural families from prokaryotic and eukaryotic organisms is
      reported. The sequences of these enzymes were multiply aligned to 427 homologous
      proteins from mesophiles and thermophiles. The net flux of amino acid exchanges
      from meso/thermophilic to psychrophilic enzymes was measured. To assign the
      observed preferred exchanges to different structural environments, such as
      secondary structure, solvent accessibility and subunit interfaces, homology
      modeling was utilized to predict the secondary structure and accessibility of
      amino acid residues for the psychrophilic enzymes for which no experimental three
      dimensional structure is available. Our results show a clear tendency for the
      charged residues Arg and Glu to be replaced at exposed sites on alpha-helices by
      Lys and Ala, respectively, in the direction from 'hot' to 'cold' enzymes. Val is
      replaced by Ala at buried regions in alpha-helices. Compositional analysis of
      psychrophilic enzymes shows a significant increase in Ala and Asn and a decrease
      in Arg at exposed sites. Buried sites in beta-strands tend to be depleted of VAL:
      Possible implications of the observed structural variations for protein stability
      and engineering are discussed.

PMID- 11342710
TI  - Different strategies to recover the activity of monomeric triosephosphate
      isomerase by directed evolution.
AB  - A monomeric version of triosephosphate isomerase from Trypanosoma brucei,
      MonoTIM, has very low activity, and the same is true for all of the additional
      monomeric variants so far constructed. Here, we subjected MonoTIM to directed
      evolution schemes to achieve an activity improvement. The construction of a
      suitable strain for genetic selection provided an effective way to obtain active
      catalysts from a diverse population of protein variants. We used this tool to
      identify active mutants from two different strategies of mutagenesis: random
      mutagenesis of the whole gene and randomization of loop 2. Both strategies
      converged in the isolation of mutations Ala43 to Pro and Thr44 to either Ala or
      Ser, when randomizing the entire gene or to Arg in the case of randomization of
      loop 2. The kinetic characterization of the two more active mutants showed an
      increase of 11-fold in k(cat) and a reduction of 4-fold in K(m) for both of them,
      demonstrating the sensitivity of the selection method. A small difference in
      growth rate is observed when both mutant genes are compared, which seems to be
      attributable to a difference in solubility of the expressed proteins.

PMID- 11342711
TI  - Characterization of the amino acids essential for the photo- and radioprotective
      effects of a Bowman-Birk protease inhibitor-derived nonapeptide.
AB  - The Bowman-Birk protease inhibitor has been reported to exert photo- and
      radioprotective activity. This effect was assigned to a cyclic nonapeptide
      sequence which is known to contain the amino acids responsible for the anti
      chymotryptic activity of the BBI. The present study indicated that linearization
      of the nonapeptide resulted in a significant loss of anti-proteolytic activity,
      whereas the photo- and radioprotective capacity persisted. Substitution of the
      amino acids Leu or Ser of the nonapeptide, essential for the anti-proteolytic
      activity, with different amino acids, indicated that rather the hydrophobic
      features of the amino acids in this position than charge are critical to retain
      the photo- and radioprotective effect. These results suggest the existence of a
      bifunctional peptide sequence with anti-proteolytic and photo-/radioprotective
      capacity. However, the lack of correlation between the photo-/radioprotective
      activity and the anti-proteolytic activity within the peptides generated by
      modification of the linear nonapeptide argues for the existence of two closely
      colocalized domains within the nonapeptide responsible for photo-/radioprotection
      and protease inhibition.

PMID- 11342712
TI  - Analysis of a conserved hydrophobic pocket important for the thermostability of
      Bacillus pumilus chloramphenicol acetyltransferase (CAT-86).
AB  - Site-directed mutagenesis was carried out on Bacillus pumilus chloramphenicol
      acetyltransferase (CAT-86) to determine the effects of substitution at a
      conserved hydrophobic pocket identified earlier as important for thermostability.
      Mutations were introduced that would substitute residues at consensus positions
      33, 191 and 203 in the enzyme, both individually and in combination. Two mutants,
      SDM1 (CAT-86 Y33F, A203V) and SDM5 (CAT-86 A203I), were more thermostable than
      wild-type and two mutants, SDM4 (CAT-86 I191V) and SDM7 (CAT-86 A203G), were less
      stable. Reconstruction of the residues of this hydrophobic pocket to that of a
      more thermostable CAT-R387 enzyme pocket (as a Y33F, I191V, A203V triple mutant)
      increased the thermostability of the enzyme above the wild-type, but its
      stability was less than that of SDM1 and SDM5. The K(m) values of the mutant
      enzymes for chloramphenicol and acetyl-CoA were essentially unaltered (in the
      ranges 15-30 and 26-35 microM respectively) and the specific activity of purified
      enzyme was in the range 270-710 units/mg protein. The possible effects of the
      amino acid substitutions on the CAT-86 structure were determined by homology
      modelling. A reduction in conformational strain and optimized hydrophobic
      interactions are predicted to be responsible for the increased thermostability of
      the SDM1 and SDM5 mutants.

PMID- 11342713
TI  - Do domain interactions of glycosyl hydrolases from Clostridium thermocellum
      contribute to protein thermostability?
AB  - Cellulolytic and hemicellulolytic enzymes usually have a domain composition. The
      mutual influence of a cellulose-binding domain and a catalytic domain was
      investigated with cellobiohydrolase CelK and xylanase XynZ from Clostridium
      thermocellum. CelK is composed of an N-terminal family IV cellulose-binding
      domain (CBDIV(CelK)), a family 9 glycosyl hydrolase domain (Gh9(CelK)) and a
      dockerin domain (DD). CelK without the DD, (CBDIV-Gh9)(CelK) and CBDIV(CelK)
      bound cellulose. The thermostability of (CBDIV-Gh9)(CelK) was significantly
      higher than that of CBDIV(CelK) and Gh9(CelK). The temperature optima of (CBDIV
      Gh9)(CelK) and Gh9(CelK) were 65 and 45 degrees C, respectively. XynZ consists of
      an N-terminal feruloyl esterase domain (FAE(XynZ)), a linker (L), a family VI CBD
      (CBDVI(XynZ)), a DD and a xylanase domain. FAE(XynZ) and (FAE-L-CBDVI)(XynZ),
      used in the present study did not bind cellulose, but both were highly
      thermostable. Replacement of CBDVI(XynZ) with CBDIV(CelK) resulted in chimeras
      with feruloyl esterase activity and the ability to bind cellulose. CBDIV(CelK)
      FAE(XynZ) bound cellulose with parameters similar to that of (CBDIV-Gh9)(CelK).
      (FAE-L)(XynZ)-CBDIV(CelK) and FAE(XynZ)-CBDIV(CelK) had lower relative affinities
      and binding capacities than those of (CBDIV-Gh9)(CelK). The three chimeras were
      much less thermostable than FAE(XynZ) and (FAE-L-CBDVI)(XynZ). The results
      indicate that domains of glycosyl hydrolases are not randomly combined and that
      domain interactions affect properties of these domain-structured enzymes.

PMID- 11342714
TI  - Stabilization of apoflavodoxin by replacing hydrogen-bonded charged Asp or Glu
      residues by the neutral isosteric Asn or Gln.
AB  - Knowledge of protein stability principles provides a means to increase protein
      stability in a rational way. Here we explore the feasibility of stabilizing
      proteins by replacing solvent-exposed hydrogen-bonded charged Asp or Glu residues
      by the neutral isosteric Asn or GLN: The rationale behind this is a previous
      observation that, in some cases, neutral hydrogen bonds may be more stable that
      charged ones. We identified, in the apoflavodoxin from Anabaena PCC 7119, three
      surface-exposed aspartate or glutamate residues involved in hydrogen bonding with
      a single partner and we mutated them to asparagine or glutamine, respectively.
      The effect of the mutations on apoflavodoxin stability was measured by both urea
      and temperature denaturation. We observed that the three mutant proteins are more
      stable than wild-type (on average 0.43 kcal/mol from urea denaturation and 2.8
      degrees C from a two-state analysis of fluorescence thermal unfolding data). At
      high ionic strength, where potential electrostatic repulsions in the acidic
      apoflavodoxin should be masked, the three mutants are similarly more stable (on
      average 0.46 kcal/mol). To rule out further that the stabilization observed is
      due to removal of electrostatic repulsions in apoflavodoxin upon mutation, we
      analysed three control mutants and showed that, when the charged residue mutated
      to a neutral one is not hydrogen bonded, there is no general stabilizing effect.
      Replacing hydrogen-bonded charged Asp or Glu residues by Asn or Gln,
      respectively, could be a straightforward strategy to increase protein stability.

PMID- 11342715
TI  - Folding screening assayed by proteolysis: application to various cystine deletion
      mutants of vascular endothelial growth factor.
AB  - The production of recombinant proteins in Escherichia coli often leads to the
      formation of inclusion bodies. Although this has a number of advantages, a major
      disadvantage is the need to develop folding protocols for the renaturing of the
      proteins. However, the systematic screening of folding conditions is often
      hampered by the lack of convenient assays to detect correctly folded proteins. To
      address this problem we present a simple protocol, which combines folding screens
      and limited proteolysis to rapidly assess and optimize folding conditions. The
      efficacy of this method, termed FSAP (folding screening assayed by proteolysis),
      is demonstrated by the large-scale folding, purification and crystallization of
      various cystine deletion mutants of the cystine knot family member: vascular
      endothelial growth factor (VEGF). These mutants are particularly difficult to
      fold as the cystine knot is believed to make major contributions to the stability
      of the protein and this family of proteins lacks extensive hydrophobic core
      regions.

PMID- 11342716
TI  - Selection of novel ligands from a whole-molecule randomly mutated C5a library.
AB  - Novel antagonists of the proinflammatory leukocyte chemoattractant C5a have been
      produced from a phage display library of whole-molecule random mutants. The cDNA
      for the inflammatory polypeptide C5adR(74) was used as template in a PCR reaction
      doped with the mutagenic nucleoside triphosphates dPTP [dP: 6-(2-deoxy-beta-D
      ribofuranosyl)-3,4-dihydro-8H-pyrimido-[4,5-c][1,2]oxazin-7-one] and 8-oxodGTP (8
      oxodG: 8-oxo-2'-deoxyguanosine) to allow the introduction of mutations in a
      highly controlled manner throughout the cDNA. The resultant library of mutants
      was displayed on bacteriophage M13 using a jun/fos linker sequence. Functional
      polypeptides were isolated by several rounds of selection against the receptor
      for C5a expressed on the surface of CHO cells. From this selection procedure, a
      limited number of variants of C5adR(74) were obtained. When expressed as free
      polypeptide, the binding affinities of the selected C5adR(74) sequences were
      increased 5-fold relative to wild-type protein. Site-directed mutagenesis of the
      C-terminus of these variants resulted in the production of antagonists of
      C5adR(74) activity.

PMID- 11342717
TI  - Enzymatically mediated engineering of multivalent MHC class II-peptide chimeras.
AB  - We previously reported the genetic engineering of the first soluble, bivalent
      major histocompatibility complex (MHC) class II-peptide ligand for T-cell
      receptor (TCR). This ligand binds stably and specifically to cognate T-cells and
      exhibits immunomodulatory effects in vitro and in vivo. The increase in valence
      of MHC class II-peptide ligands was shown to parallel their avidity for cognate
      TCRs and potency in stimulating cognate T-cells. We describe a new enzymatic
      method to increase the valence of MHC-peptide ligands by cross-linking the N
      glycan moieties of dimeric MHC II-peptide units through a flexible, bifunctional
      polyethylene glycol linker. Using this method, we generated covalently stabilized
      tetravalent and octavalent MHC II-peptide ligands which bound stably and
      specifically to cognate TCR and preserved their structural integrity in blood and
      lymphoid organs for 72 h. Depending on the TCR/CD4 occupancy and degree of
      TCR/CD4 co-clustering, the multivalent MHC II-peptide ligands polarized
      efficiently the antigen-specific CD4(+) T-cells toward type 2 cell
      differentiation or induced T-cell anergy and apoptosis. The enzymatically
      mediated engineering of multivalent MHC-peptide ligands for cognate TCRs may
      provide rational grounds for the development of new therapeutic agents endowed
      with strong modulatory effects on antigen-specific T-cells.

PMID- 11342718
TI  - Characterization of glycosylated variants of beta-lactoglobulin expressed in
      Pichia pastoris.
AB  - Glycosylated variants of beta-lactoglobulin (BLG) were produced in the
      methylotrophic yeast Pichia pastoris to mimic the glycosylation pattern of
      glycodelin, a homologue of BLG found in humans. Glycodelin has three sites for
      glycosylation, corresponding to amino acids 63-65 (S1), 85-87 (S2) and 28-30 (S3)
      of BLG. These three sites were engineered into BLG to produce the variants S2,
      S12 and S123, which carried one, two and three glycosylation sites, respectively.
      The oligosaccharides on these BLG variants ranged from (mannose)(9)(N
      acetylglucosamine)(2) (Man(9)GN(2)) to Man(15)GN(2) and were of the alpha-linked
      high mannose type. The variant S123 exhibited highest levels of glycosylation,
      with the range of glycans being Man(9-14)GN(2). Digestion of S123 with alpha-1,2
      linkage specific mannosidase resulted in a single product corresponding to
      Man(6)GN(2). These results indicated a glycosylation pattern consisting of a
      Man(5)GN(2) structure extended by 4-9 mannose residues attached mainly by alpha
      1,2 linkages. The results also indicated extension of the Man(5)GN(2) structure
      by a single alpha-1,6-linked mannose. The N-linked glycosylation pathway in
      P.pastoris is significantly different from that in Saccharomyces cerevisiae, with
      the addition of shorter outer chains to the core and no alpha-1,3 outer
      extensions.

PMID- 11342719
TI  - Industry-sponsored research in minimally invasive surgery.
AB  - In many disciplines, including minimally invasive surgery, pharmaceutical and
      instrument companies are major sources of industry-sponsored research. There are
      two types of such research, industry-initiated and investigator-initiated.
      Distinction between them is sometimes blurred. In industry-sponsored research a
      conflict may occur between clinicians and sponsor. In all cases, a clinical trial
      should be done properly and ethically, and results, whether negative or positive,
      should be published. Disposition of intellectual property and authorship should
      be established before starting the trial.

PMID- 11342720
TI  - A system of credentialing physicians in advanced gynecologic endoscopy.

PMID- 11342721
TI  - Retained fetal bones in the uterine cavity.
AB  - A 33-year-old woman was referred for infertility of 5 years' duration. Her
      history included pregnancy terminations at 6 weeks' gestation in 1992 and at 16
      weeks' gestation in 1993. Both abortions were performed by curettage in West
      Africa. Her menses were every 28 days with normal flow. Due to a suggestion of a
      filling defect in the uterus on hysterosalpingography, hysteroscopic examination
      was performed. At hysteroscopy, several fragments of fetal bones were present in
      the uterus. These appeared as white structures, some with trabeculated pattern.
      They were removed until the entire uterine cavity was devoid of bony fragments.
      Histopathology examination confirmed the diagnosis. It is very likely that the
      findings were related to the woman's abortion in 1993. Similar to intrauterine
      contraceptive devices, fetal bones in the uterine cavity prevent conception.

PMID- 11342722
TI  - Venous air and gas emboli in operative hysteroscopy.
AB  - Air and gas emboli have been reported in almost all areas of clinical and
      surgical practice. The literature is replete with observations and methods for
      treating these events. It is possible to mitigate the consequences of this risk,
      particularly in operative hysteroscopy. Recommendations include monitoring
      devices such as capnography to facilitate intraoperative diagnosis of these
      emboli.

PMID- 11342723
TI  - Hysteroscopy and gynecology: past, present, and future.

PMID- 11342724
TI  - Hysteroscopy may be the method of choice for management of residual trophoblastic
      tissue.
AB  - STUDY OBJECTIVE: To assess the efficacy of and reproductive outcome after
      selective curettage of residual trophoblastic tissue directed by hysteroscopy
      compared with conventional, nonselective, blind curettage. DESIGN: Retrospective
      analysis (Canadian Task Force classification II-1). SETTING: Tertiary care
      medical center. PATIENTS: Seventy patients after curettage or delivery, with
      clinical and ultrasonographic signs of suspected residual trophoblastic tissue.
      MEASUREMENTS AND MAIN RESULTS: Twenty-four women underwent traditional curettage
      and 46 underwent hysteroscopic selective curettage. Five (20.8%) patients who
      underwent traditional curettage later required operative hysteroscopy due to
      persistent residual tissue. None of those who underwent hysteroscopic selective
      curettage needed a second operation. No patient in either group experienced
      anesthetic complications, perforation of the uterus, fluid overload, or other
      surgical complication. Reproductive outcome was similar in both groups, with
      tendency to conceive earlier in the hysteroscopy group, but no difference in
      overall pregnancy rates. CONCLUSION: Operative hysteroscopy for selective
      curettage of residual trophoblastic tissue should be considered an alternative to
      nonselective, blind curettage.

PMID- 11342725
TI  - Effects of local bupivacaine instillation on pain after laparoscopy.
AB  - STUDY OBJECTIVE: To evaluate the effect of preincisional and intraperitoneal
      bupivacaine administration on immediate and late pain after operative
      laparoscopy. DESIGN: Randomized study (Canadian Task Force classification I).
      SETTING: University teaching hospital. PATIENTS: One hundred fifty women
      undergoing laparoscopy for various gynecologic indications. INTERVENTION: A dose
      of 0.5% bupivacaine 10 ml (50 mg) was injected into cannula sites before
      incisions and another 10 ml diluted with 100 ml saline into the peritoneal cavity
      at completion of the procedure. Equal amount of physiologic saline was used in
      controls. MEASUREMENTS AND MAIN RESULTS: Modified McGill pain intensity scores
      and amount of analgesic required in the recovery room and within 24 hours
      postoperatively were evaluated. Of 150 women, 142 completed the study (71
      bupivacaine group, 71 controls). Groups did not differ significantly in body mass
      index, duration of surgery, return to consciousness, and analgesic requirement
      during 3-hour observation in the recovery room and 24 hours after discharge. Pain
      scores were highest 30 minutes after the procedure in both groups. At that time
      the pain score in the bupivacaine group was lower than that in the control group
      (1.8 +/- 0.2 vs 2.3 +/- 0.2, p <0.05). Beyond that time, the groups did not
      differ in pain scores and analgesic requirements. CONCLUSION: Postoperative pain
      is the highest within 30 minutes after laparoscopy. Local instillation of
      bupivacaine before incision and intraperitoneally was effective in reducing pain
      immediately after operative laparoscopy, but the effect was not seen beyond 30
      minutes.

PMID- 11342726
TI  - Accuracy of hysteroscopy in predicting histopathology of endometrium in 1500
      women.
AB  - STUDY OBJECTIVE: To estimate the accuracy of hysteroscopy in predicting
      endometrial histopathology. DESIGN: Retrospective analysis (Canadian Task Force
      classification II-2). SETTING: Public hospital. PATIENTS: One thousand five
      hundred women undergoing diagnostic hysteroscopy for suspected endometrial
      pathology, mostly because of abnormal uterine bleeding. INTERVENTIONS:
      Hysteroscopy and endometrial biopsy. MEASUREMENTS AND MAIN RESULTS: Hysteroscopy
      imaging was matched with histology. Functional, dysfunctional, and atrophic
      endometrium were considered normal findings; endometritis, endometrial polyps,
      hyperplasia, and carcinomas were considered abnormal. Sensitivity, specificity,
      and negative (NPV) and positive (PPV) predictive values of hysteroscopy in
      detecting normal or abnormal endometrium were calculated. These figures were
      defined to assess hysteroscopic accuracy in estimating pathologic conditions.
      Histology showed normal endometrium in 927 patients. Endometritis, polyps,
      hyperplasia, and malignancies were found in 21, 265, 185, and 102 patients,
      respectively. Hysteroscopy showed sensitivity, specificity, NPV, and PPV of
      94.2%, 88.8%, 96.3%, and 83.1%, respectively, in predicting normal or abnormal
      histopathology of endometrium. Highest accuracy was in diagnosing endometrial
      polyps, with sensitivity, specificity, NPV, and PPV of 95.3%, 95.4%, 98.9%, and
      81.7%, respectively; the worst result was in estimating hyperplasia, with
      respective figures of 70%, 91.6%, 94.3%, and 60.6%. All failures of hysteroscopic
      assessment resulted from poor visualization of the uterine cavity or from
      underestimation or overestimation of irregularly shaped endometrium. CONCLUSION:
      Hysteroscopy was accurate in distinguishing between normal and abnormal
      endometrium. Nevertheless, better knowledge of relationship between hysteroscopic
      imaging and pathophysiologic states of endometrium is necessary to improve its
      accuracy. Endometrial sampling is recommended in all hysteroscopies showing
      unevenly shaped and thick endometrial mucosa or an anatomically distorted uterine
      cavity, and when endouterine visualization is less than optimal.

PMID- 11342727
TI  - A system of credentialing physicians in advanced gynecologic endoscopy.
AB  - STUDY OBJECTIVE: To develop criteria for credentialing physicians in advanced
      gynecologic endoscopy. DESIGN: Descriptive study (Canadian Task Force
      classification III). SETTING: University-affiliated community hospital. Patients.
      None. INTERVENTION: Criteria for credentialing physicians were tested.
      MEASUREMENTS AND MAIN RESULTS: Physicians were granted universal privileges in
      advanced gynecologic laparoscopy or hysteroscopy when they were certified by the
      Accreditation Council for Gynecologic Endoscopy (ACGE). Alternatively, they
      received category-specific privileges in any one of six categories when they
      provided documentation of having satisfactorily performed 10 cases in four
      categories or 5 cases in the remaining two. Required cases included those
      performed during residency or with a proctor. Completion of an approved
      residency, board certification or eligibility, and good standing were other
      requirements. Proof of continuing medical education in endoscopy was also
      considered. Of 31 physicians in the department, 3 had ACGE certification: 1 in
      laparoscopy, 2 in laparoscopy and hysteroscopy. Three physicians gained
      privileges under the alternative system. One received category 1, one received
      categories 1 and 2, and the third received categories 1, 2, and 6 privileges.
      Twenty-five physicians were granted standard endoscopy privileges, including six
      who applied for advanced endoscopy privileges. These applications are pending
      case documentation and proctorship. CONCLUSION: A system for credentialing
      physicians in advanced gynecologic endoscopy, using two alternative pathways, was
      implemented.

PMID- 11342728
TI  - Salpingoscopic and laparoscopic investigations in relation to fertility outcome.
AB  - STUDY OBJECTIVE: To evaluate the correlation between salpingoscopic and
      laparoscopic findings and their relation to reproductive outcomes. DESIGN:
      Prospective study (Canadian Task Force classification II-2). SETTING: University
      affiliated hospital. PATIENTS: Ninety-one infertile women. INTERVENTION:
      Salpingoscopy and laparoscopy. MEASUREMENTS AND MAIN RESULTS: Salpingoscopic
      findings were expressed according to a widely used classification. Tubal
      morphology at laparoscopy was defined as regular (normal morphology), convoluted
      (any kind of distortion or adhesion), or hydrosalpinx. Laparoscopic and
      salpingoscopic findings did not correlate. Seventeen pregnancies occurred within
      1 year from the procedures. According to life table analysis, the cumulative
      pregnancy rate was significantly higher in women with endotubal morphology
      showing minimal or no tubal damage, than in women with higher grades of endotubal
      damage. Conversely, tubal morphology at laparoscopy was not able to predict
      pregnancy outcome. CONCLUSION: Laparoscopy alone might not be sufficient to
      predict tubal integrity. Performing salpingoscopy with laparoscopy could
      significantly increase accuracy in predicting short-term fertility outcome. Given
      its low complication rate and brief duration, salpingoscopy should have a primary
      role in management of infertility.

PMID- 11342729
TI  - Hysteroscopic and immunohistochemical findings in type I and type II endometrial
      carcinomas.
AB  - STUDY OBJECTIVE: To determine whether types I and II endometrial carcinomas have
      different precursor lesions recognized at hysteroscopy and immunohistochemistry.
      DESIGN: Single center case study (Canadian Task Force classification II-2).
      SETTING: A private, university affiliated hospital. PATIENTS: One hundred forty
      six postmenopausal women with endometrial pathology diagnosed by hysteroscopy and
      biopsy. INTERVENTION: Hysteroscopy and immunohistochemical determination of p53
      overexpression. MEASUREMENTS AND MAIN RESULTS: The number of cells showing p53
      overexpression was low in endometrial polyps, hyperplasia, and G1 endometrioid
      carcinomas. A marked increase was seen only in high-grade G2-G3 endometrioid
      carcinomas and in cases of uterine papillary serous carcinoma. In the latter,
      strong p53 overexpression was detected in early forms still confined to
      endometrial polyps. Hysteroscopy could not differentiate between high- and low
      grade endometrioid carcinomas. CONCLUSION: The p53-driven pathway plays an
      important role in the origin of papillary serous carcinoma but not in G1
      endometrioid cancer that evolves from estrogen-stimulated endometrium. However,
      this pathway is important for progression of low-grade endometrioid carcinomas to
      higher-grade tumors.

PMID- 11342730
TI  - Laparoscopic myomectomy: technique, complications, and ultrasound scan
      evaluations.
AB  - STUDY OBJECTIVE: To evaluate the feasibility, limits, and complications of
      laparoscopic myomectomy, assess time to full recovery, and evaluate uterine wound
      healing by ultrasound in the early postoperative period. DESIGN: Prospective
      study (Canadian Task Force classification II-2). SETTING: General hospital.
      PATIENTS: Three hundred sixty-eight women undergoing laparoscopic myomectomy.
      INTERVENTION: Laparoscopic myomectomy and laparoscopic and/or hysteroscopic
      treatment of associated pathologies. MEASUREMENTS AND MAIN RESULTS: In these
      women 768 myomas were removed laparoscopically. Mean operating time was 100.78 +/
      43.83 minutes, mean decreases in hemoglobin and hematocrit were 1.38 +/- 0.93
      g/100 ml and 4.8 +/- 2.9 g/100 ml, respectively, and mean length of hospital stay
      was 2.89 +/- 1.3 days. Intraoperative complications occurred in 12 patients
      (3.34%) and intraoperative transfusion of autologous blood was required in 10.
      Main postoperative complications were continuing hemorrhage requiring blood
      transfusion in three women and second laparoscopy in two. Pyrexia occurred in 12
      patients. Average time to full recovery was 10.58 +/- 6.68 days. At 1-month
      follow-up 12 of 282 women developed further complications: abdominal pain 5,
      vaginitis 4, metrorrhagia 2, and dysuria 1. Sonographic evaluation of the uterine
      scar showed a highly echogenic area with ill-defined margins. In 81 women who had
      sonographic evaluation 30 days postoperatively, the uterine scar was reduced by
      an average of 44.1% (p <0.001). Of 176 patients screened at day 30, 6 (3.4%) had
      anechoic areas adjacent to the uterine scar, possibly due to hematoma. A
      previously unknown myoma, two ovarian cysts, and two pelvic hematoma were also
      discovered. CONCLUSION: . Laparoscopic myomectomy is effective and relatively
      safe. In skilled hands it has a low risk of complications and appears to be a
      valid alternative to the open procedure. Sonographic assessment allows detection
      of alterations in muscular echotexture, but its effectiveness in identifying
      women at risk of uterine rupture or dehiscence has to be proved.

PMID- 11342731
TI  - Laparoscopic bipolar coagulation of uterine vessels to treat symptomatic myomas
      in women with elevated Ca 125.
AB  - STUDY OBJECTIVE: To assess laparoscopic bipolar coagulation of uterine vessels
      (LBCUV) for symptomatic myomas in women with elevated CA 125 (>35 U/ml). DESIGN:
      Prospective, longitudinal study (Canadian Task Force classification II-1).
      SETTING: Private practice, university-affiliated hospital. PATIENTS: Forty-six
      women (age 30-50 yrs) with symptomatic myomas and elevated CA 125 level.
      INTERVENTION: Laparoscopic bipolar coagulation of uterine vessels performed over
      10 months. MEASUREMENTS AND MAIN RESULTS: All patients underwent successful LBCUV
      and coagulation of anastomotic site of uterine arteries with ovarian arteries
      without intraoperative complication. One, 3, and 6 months after treatment,
      respectively, 52.2%, 65.2%, and 71.7% of women reported improvement in
      menorrhagia, 19.6%, 45.7%, and 56.5% noted improvement in dysmenorrhea, and 6.5%,
      16.1%, and 38.7% had improvement in bulk-related symptoms. Average reduction in
      uterine volume was 9.1%, 16.9%, and 38.3% and average reduction in dominant myoma
      was 12.1%, 23.9%, and 59.1% at those times; the average reduction of CA 125 in
      all patients was 39.8, 75.4, and 126.1U/ml. CONCLUSION: Symptoms were improved
      and uterine volume and dominant myoma were reduced by LBCUV. The CA 125 level
      fell during follow-up in 40 patients (87.0%). Improvement in symptoms, especially
      menorrhagia, and shrinkage of uterine volume and dominant myoma seemed to be more
      pronounced in women with decreased than in those without decreased CA 125 after
      treatment (p = 0.045). The CA 125 level may be a valuable indicator for
      monitoring the efficacy of LBCUV.

PMID- 11342732
TI  - Effect of heating and humidifying gas on patients undergoing awake laparoscopy.
AB  - STUDY OBJECTIVE: To determine the effect of heating and humidifying CO2 on the
      tolerance of awake laparoscopy and frequency of shoulder pain and patient
      recovery. DESIGN: Randomized, controlled study (Canadian Task Force
      classification I). SETTING: University-affiliated hospital. PATIENTS: Forty
      consecutive women. INTERVENTION: Awake laparoscopy with and without heating and
      humidifying CO2. MEASUREMENTS AND MAIN RESULTS: Heating and humidifying CO2
      decreased the frequency of shoulder pain and increased tolerance of the
      procedure. Thirty percent of patients required no intravenous sedation and did
      not experience shoulder pain when 3 L of gas or 15 mm Hg pressure was achieved.
      When shoulder pain did occur with heated and humidified gas, it was brief.
      CONCLUSION: Heating and humidifying CO2 increases tolerance of awake laparoscopy
      and decreases the frequency and duration of shoulder pain.

PMID- 11342733
TI  - Bipolar electrical energy in physiologic solution--a revolution in operative
      hysteroscopy.
AB  - STUDY OBJECTIVE: To evaluate the feasibility and efficiency of operative
      hysteroscopy in physiologic saline solution. DESIGN: Prospective observational
      study (Canadian Task Force classification II-2). SETTING: Tertiary university
      hospital. PATIENTS: One hundred sixteen women (56% menopausal) with intrauterine
      pathology with or without symptoms, in whom malignancy was excluded by
      endometrial sampling. INTERVENTION: Operative hysteroscopy for resection of
      uterine septa, lysis of adhesions, and resection of myomas or polyps using a
      bipolar electrical energy system (VersaPoint) developed for this purpose.
      MEASUREMENTS AND MAIN RESULTS: Polyps were significantly more common in
      menopausal than in premenopausal women. Symptoms (mainly bleeding) occurred in
      66.9% of premenopausal and 74.5% of menopausal patients. Endometrial polyps and
      submucous myomata were associated with symptoms in 68% and 70%, respectively.
      Operating time was less than 25 minutes. Two specimens revealed malignancy. One
      uncomplicated uterine perforation occurred. CONCLUSION: This new technique has
      the potential to replace monopolar-based intrauterine interventions and may
      become the treatment of choice for benign intrauterine pathology.

PMID- 11342734
TI  - Laparoscopic repair of ureteral injuries.
AB  - STUDY OBJECTIVE: To assess the outcome of laparoscopic repair of pelvic ureter
      injuries. DESIGN: Retrospective case series (Canadian Task Force classification
      II-2). SETTING: Large urban tertiary care medical center. PATIENTS: Four women
      who had pelvic ureter injuries and laparoscopic repair during laparoscopic
      gynecologic procedures. INTERVENTION: Laparoscopic ureteroureterostomy.
      MEASUREMENTS AND MAIN RESULTS: All injuries were identified immediately and
      repaired laparoscopically. No patient required repeat surgery. On assessment by
      physical examination, serum creatinine, and intravenous urogram, no patient had
      evidence of renal insufficiency. One woman had a narrowing at the site of
      ureteroureterostomy 6 weeks after repair; it was resolved on urogram 8 months
      after the injury. CONCLUSION: Laparoscopic ureteroureterostomy is feasible in
      some cases of ureteral injury. Experience with laparoscopic suturing is necessary
      to perform this procedure.

PMID- 11342735
TI  - Clinical utility of pelvic pain mapping.
AB  - STUDY OBJECTIVE: To survey physicians' opinions concerning the impact of pelvic
      pain mapping on clinical management and surgical decisions. DESIGN: Opinions of
      physicians based on clinical experience (Canadian Task Force classification III).
      SETTING: Evening meetings appended to two national meetings. MEASUREMENTS AND
      MAIN RESULTS: After viewing videotaped interviews, physical examinations,
      standard laparoscopy, and pelvic pain mapping at laparoscopy in two patients,
      practicing gynecologists completed questionnaires recording their opinions about
      the utility of pelvic pain mapping. A second group of gynecologists viewed only
      one tape. The first group considered pain mapping to be moderately or extremely
      useful (patient 1, 57.9%; patient 2, 73.7%). Mapping data either made surgeons
      change the surgical procedure they would have chosen or further clarified the
      diagnosis (patient 1, 68.4%; patient 2, 84.2%). Of the second group of 67
      surgeons, 73% thought that mapping results would have made them change their
      surgical approach. CONCLUSION: In appropriate cases, pelvic pain mapping during
      microlaparoscopy under conscious sedation can provide information that may
      influence surgical decisions as well as general clinical management.

PMID- 11342736
TI  - Vaginal expulsion of submucous myomas after laparoscopic-assisted uterine
      depletion of the myomas.
AB  - STUDY OBJECTIVE: To determine the safety and side effects that may be caused by
      laparoscopic-assisted uterine depletion (LAUD) of submucous myomas. DESIGN:
      Retrospective chart review and follow-up (Canadian Task Force classification II
      2). SETTING: University-affiliated tertiary referral center. PATIENTS: Five
      hundred twenty women with symptomatic myomas warranting surgical treatment, who
      wished to retain their uteri. INTERVENTION: Laparoscopic bipolar coagulation of
      uterine arteries and anastomotic sites of uterine arteries with ovarian arteries.
      MEASUREMENTS AND MAIN RESULTS: Postoperative sonographs showed submucous myomas
      in 53 (10.2%) women. During follow-up for a mean of 8.6 months very few
      complications occurred; however, nine women (1.7%) experienced vaginal expulsion
      of myomas from 2 weeks to 5 months postoperatively. Four of them were readmitted
      within 43 days with high fever and fetid discharge, and cervical cultures
      revealed heavy growth of Escherichia coli in three. Vaginal myomectomy was
      performed in six patients, and one woman passed the myoma spontaneously.
      Histopathologic studies of these nine specimens showed that two had infarction,
      three had coagulative necrosis, and four had degeneration. After treatment, all
      nine women had normal menstruation and their symptoms resolved during follow-up
      of at least 3 months. CONCLUSION: In our experience LAUD led to satisfactory
      symptomatic improvement and reduction in myoma volume and few complications. If
      vaginal expulsion of submucous fibroids can be viewed as a side effect, we should
      pay close attention to women with submucous myomas, especially within 2 months of
      LAUD. Otherwise, more dangerous complications could occur.

PMID- 11342737
TI  - Reoperative hysteroscopic surgery in the management of patients who fail
      endometrial ablation and resection.
AB  - STUDY OBJECTIVE: To determine the safety and efficacy of reoperative
      hysteroscopic surgery for women who fail endometrial ablation and resection.
      DESIGN: Retrospective chart review and follow-up (Canadian Task Force
      classification II-2). SETTING: Private office practice. PATIENTS: Twenty-six
      women who had undergone endometrial ablation or resection and experienced failure
      characterized by intolerable pain, bleeding, or asymptomatic hematometra.
      INTERVENTION: Sonographically guided hysteroscopic endomyometrial resection.
      MEASUREMENTS AND MAIN RESULTS: Mean length of time from initial treatment for
      abnormal uterine bleeding and reoperative hysteroscopic surgery was 41.2 +/- 47.9
      months. Five (19.2%) women required simple dilatation and 21 (80.8%) required
      endocervical resection to achieve access to the uterine cavity. There were no
      operative complications. Mean operating time was 20.3 +/- 9.5 minutes. Mean
      specimen weight was 6.7 +/- 4.9 g. Adenomyosis was present in 15 (57.7%)
      specimens. Women were followed for a mean of 23.2 +/- 22.7 months. Twenty-three
      (88.5%) achieved satisfactory results and avoided hysterectomy. Three women
      (11.5%) eventually required hysterectomy because of recurrent pain or bleeding.
      CONCLUSION: Reoperative hysteroscopy is useful in managing women after failed
      endometrial ablation and resection. It produces excellent results in achieving
      amenorrhea and relief of cyclic pelvic pain, thereby avoiding hysterectomy in
      most patients.

PMID- 11342738
TI  - Benign or malignant ovarian neoplasms and ovarian endometriomas.
AB  - STUDY OBJECTIVE: To investigate clinical features and biologic behavior of
      ovarian cancer that might be closely related to endometrioma and/or
      endometriosis. DESIGN: Retrospective study (Canadian Task Force classification II
      2). SETTING: University hospital. PATIENTS: All 324 women who were operated for
      endometriomas and/or ovarian tumors 5 cm or greater in diameter between January
      1988 and December 1997. INTERVENTION: One hundred twelve women underwent
      laparoscopic surgery and 212 had laparotomy. MEASUREMENTS AND MAIN RESULTS: All
      tissues were evaluated histologically. Clinical examinations including ultrasound
      and serum tumor makers were performed in all patients preoperatively. No
      malignancies were found at laparoscopic surgery (76 endometriomas, 36 ovarian
      tumors). The frequency of endometriosis in benign, borderline malignant, and
      malignant tumors was 9.7%, 12.5%, and 11.4%, respectively. Endometriosis was
      present most frequently (40%) in women with endometrioid adenocarcinoma. It was
      present in 81 patients with endometriomas and 25 with ovarian neoplasms. Of
      these, nine women (8.5%) had malignant tumors, including borderline malignancy.
      Among patients with malignant tumors, those without endometriosis were
      significantly older (mean +/- SD age 54.9 +/- 16.2 yrs) than those with
      endometriosis elsewhere in the pelvis (45.9 +/- 8.9 yrs). CONCLUSION:
      Endometriosis may be closely related to ovarian tumors such as endometrioid
      adenocarcinoma. Surgeons should be aware of this possibility, and candidates for
      laparoscopic surgery should be carefully selected based on preoperative
      evaluations.

PMID- 11342739
TI  - Serum biochemical changes after laparoscopy may be indicators of bladder injury.
AB  - We evaluated the serum renal biochemical profile as an indicator of unrecognized
      laparoscopic bladder injury in four women. The patients were seen 24 to 56 hours
      postoperatively with elevated serum creatinine and urea levels, and electrolyte
      changes compatible with acute renal dysfunction. The mechanism responsible for
      these biochemical changes appears to be extravasation and reabsorption of urine.
      Biochemical values returned to normal within 24 hours after bladder repair.

PMID- 11342740
TI  - Pneumothorax complicating laparoscopic-assisted vaginal hysterectomy.
AB  - Right pneumothorax occurred 2 days after laparoscopic-assisted vaginal
      hysterectomy. The mechanism was most likely CO2 diffusion from pneumoperitoneum
      through a diaphragmatic defect. It is essential to be aware of this rare
      complication because of its late onset after the surgical procedure.

PMID- 11342741
TI  - Laparoscopic-assisted surgery for benign ovarian cyst in a young girl.
AB  - A 7-year-old girl was admitted to our hospital because of sudden lower abdominal
      pain and vomiting. Emergency laparoscopy and cystectomy were performed, with a
      diagnosis of torsion of an ovarian cyst. All manipulations were possible through
      a 2-cm incision in the abdominal wall.

PMID- 11342742
TI  - Laparoscopic ligation and resection of two ipsilateral interstitial pregnancies
      in the same patient.
AB  - A 31-year-old woman had bilateral interstitial-isthmic tubal anastomoses. After
      one spontaneous abortion and one term vaginal delivery, she had a right
      unruptured interstitial pregnancy that was laparoscopically ligated with
      endoloops and resected. Ten months later she experienced a second unruptured
      interstitial pregnancy on the same side. This was also laparoscopically suture
      ligated and resected uneventfully. The contralateral patent tube was ligated at
      the same time.

PMID- 11342743
TI  - An automatic camera-holding system for gynecologic laparoscopy.
AB  - Ergonomic analysis of conditions prevailing during laparoscopy show that static
      holding work causes considerable problems. The surgeon's assistant is
      particularly affected, for example, by holding the endoscope optical system. To
      minimize strain for the entire operating team and to increase the range of
      activities that can be performed by the assistant, an automatic surgical camera
      holding system was developed. Its value in clinical practice was tested in
      gynecologic laparoscopy, where it enabled the surgical team to work more
      comfortably.

PMID- 11342744
TI  - Echosight patton coaxial catheter-guided hysteroscopy.
AB  - Two women requiring assisted reproduction had cervical stenosis on diagnostic
      evaluation. Office hysteroscopy was performed with paracervical block
      supplemented with mild intravenous sedation. When cervical pathology precluded
      placement of a diagnostic hysteroscopy, an Echosight Patton coaxial catheter with
      an outer echogenic sheath (5.7F) and inner 0.018-inch diameter guidewire with
      coude tip was introduced transcervically. Intraoperative transvaginal ultrasound
      was performed to ensure proper placement into the uterine cavity. When the
      uterine cavity was identified, cervical pathology was corrected with a VersaPoint
      electrosurgical electrode with bipolar coagulation through an operative
      hysteroscope. Concomitant diagnostic laparoscopy was not necessary. Echosight
      Patton coaxial catheter-guided ultrasound is a reassuring method to confirm
      hysteroscopic placement.

PMID- 11342745
TI  - Use of the CEEA stapler to avoid ultra-low segmental resection of a full
      thickness rectal endometriotic nodule.
AB  - A woman with a history of numerous surgical episodes for treatment of aggressive
      endometriosis experienced rectal symptoms. She was prepared for the possibility
      of laparotomy with or without colostomy to relieve her symptoms. After extensive
      laparoscopic dissection of the rectovaginal septum, a circular stapling device
      (Premium Plus CEEA; Autosuture, Melbourne, Victoria, Australia) was used to
      excise completely an anterior rectal lesion that otherwise would have resulted in
      ultra-low rectal resection and anastomosis. Morbidity associated with the latter
      procedure was avoided; the patient was discharged within 72 hours and experienced
      no early or late complications. Postoperative barium enema was obviated by rapid
      return to normal bowel habits and complete resolution of dyschezia and
      dyspareunia.

PMID- 11342746
TI  - Three-year follow-up of uterine thermal balloon therapy for treatment of
      menorrhagia.

PMID- 11342748
TI  - Arrhythmia mechanisms in the new millennium.

PMID- 11342749
TI  - Cardiac conduction abnormalities in a mouse model of Lyme borreliosis.
AB  - BACKGROUND: Borrelia Burgdorferi (BB) induces cardiac conduction abnormalities in
      infected humans. Mice models of Lyme disease have been developed, however their
      electrophysiologic (EP) properties of conduction are unknown. METHODS: Seventy
      six C3H/J mice (BB infected and age- and gender-matched controls) underwent
      blinded in vivo EP studies. In a first phase of the study, 40 male C3H/J mice
      were divided into 2 groups: Group (A) mice were infected at age 3 (weeks) and
      studied at 5, and Group (B) mice were infected at 9 and studied at 11. In a
      second phase, 36 female mice were divided into 2 groups: Group (C) mice were
      infected at 3 weeks and studied at 5, and Group (D) mice were infected at 3 and
      studied at 11. RESULTS: Infected mice of group (A) and (C) had wider QRS
      complexes (21.0+/-1.6 versus 17.3+/-1.3ms, p< or =0.0001 and 20.3+/-2.1 versus
      18.5+/-1.7, p = 0.05, respectively) compared to the healthy controls (HC).
      Infected mice of group (B) and group (D) were similar to the HC. In all groups,
      the presence of conduction abnormalities correlated very closely with the amount
      of inflammation on pathology. CONCLUSION: This study describes the first EP mouse
      model of Lyme carditis. C3H/J mice exhibit conduction abnormalities that are
      reversible 8 weeks after inoculation, closely paralleling the resolution of
      inflammation on pathology. This model can be a valuable tool in the developing
      and testing of new modalities for the prevention and treatment of Lyme carditis.

PMID- 11342750
TI  - Endocardial stimulation of efferent parasympathetic nerves to the
      atrioventricular node in humans: optimal stimulation sites and the effects of
      digoxin.
AB  - The purposes of this study were to identify optimal sites of stimulation of
      efferent parasympathetic nerve fibers to the human atrioventricular node via an
      endocardial catheter and to investigate the interaction between digoxin and vagal
      activation at the end organ. METHODS: The ventricular rate was measured during
      atrial fibrillation, prior to and during parasympathetic nerve stimulation, in 8
      patients taking digoxin and in 10 controls. High frequency electrical stimuli
      were delivered via an hexapolar or quadripolar electrode catheter, placed at the
      posteroseptal right atrium near the atrioventricular node (n=18 patients) or in
      the coronary sinus (n=12 of 18 patients). In 4 patients, stimulation was repeated
      after intravenous administration of 1 to 2 mg of atropine. RESULTS: Nerve
      stimulation prolonged the R-R interval in all patients. Stimulation close to the
      posteroseptal right atrium led to maximal atrioventricular nodal slowing. The
      mean R-R intervals at baseline and during parasympathetic nerve stimulation (60
      mA) from the posteroseptal right atrium and the proximal coronary sinus were
      581+/-79 ms, 2440+/-466, and 900+/-228 ms respectively (p=0.0001). The response
      to nerve stimulation was greater in patients taking digoxin than in patients not
      taking the drug (p=0.02). Junctional rhythm occurred during nerve stimulation in
      8/8 patients taking digoxin and 0/10 not taking the drug (p=0.0001). The response
      to stimulation was eliminated after atropine (p=0.01). CONCLUSIONS:
      Parasympathetic nerves to the atrioventricular node were stimulated from the
      proximal coronary sinus as well as the posteroseptal right atrium. Stimulation at
      the posteroseptal right atrium resulted in the greatest response, and digoxin
      enhanced this response. The augmented response suggests that an interaction may
      exist between parasympathetic stimulation and digoxin at the end organ.

PMID- 11342751
TI  - Atrioventricular dissociation exacerbating posturally-induced syncope.
AB  - We report a case of an 85-year-old patient with posturally-induced syncope in
      whom symptoms were reproduced during tilt table testing in conjunction with
      development of an accelerated junctional rhythm with isorhythmic atrio
      ventricular (AV) dissociation. That loss of AV synchrony was crucial to
      development of hypotension and syncope was demonstrated during electrophysiologic
      testing in which both an accelerated junctional rhythm and an inducible atypical
      AV nodal re-entrant tachycardia (AVNRT) were induced. The accelerated junctional
      rhythm was accompanied by moderate hypotension with the patient in the supine
      posture, whereas blood pressure was well maintained during atypical AVNRT despite
      a much faster ventricular rate. Thus, symptomatic hypotension due to AV
      dissociation, presumably the result of transient autonomic disturbance, may be
      another manifestation of neurally-mediated syncope.

PMID- 11342752
TI  - Cardiac swelling associated with linear radiofrequency ablation in the atrium.
AB  - OBJECTIVES: To characterize myocardial swelling in response to application of
      endocardial radio-frequency ablation lesions. BACKGROUND: In individual patients,
      we have observed that ablation in the posterior right atrium was associated with
      echocardiographic evidence of atrial and contiguous right pulmonary vein wall
      swelling. METHODS: 1. Human Subjects: "linear" ablation was performed in the
      posterior right atrium in 10 subjects; a portion of the ablation lesion was
      contiguous to the right pulmonary vein; this area was defined as the "contiguity
      zone". In the contiguity zone, right atrial wall thickness and pulmonary vein
      lumen diameter were measured utilizing intracardiac echocardiography.
      Measurements were made just prior to (baseline) and immediately after ablation.2.
      Porcine Subjects: linear ablation was performed in the posterior right atrium of
      14 pigs. In the contiguity zone, atrial wall thickness, interstitial space
      thickness, right pulmonary vein wall thickness and lumen diameter were measured
      using intracardiac echocardiography. Measurements were made at baseline,
      immediately after ablation, and at 1, 4, 8 or 12 weeks after ablation (followup).
      Post-mortem pathologic evaluation of the contiguity zone was performed. RESULTS:
      1. Human Subjects: Immediately after ablation, relative to baseline right atrial
      wall thickness was significantly increased (9.4+/-3.1mm versus 5.4+/-1.5 mm) and
      right pulmonary vein lumen diameter was significantly decreased (6.2+/-2.9 mm
      versus 8.1+/-2.9 mm).2. Porcine Subjects: Immediately after ablation, right
      atrial wall thickness (4.1+/-1.2 mm), interstitial space thickness (1.9+/-1.1mm),
      and right pulmonary vein wall thickness (1.2+/-0.4 mm) were each significantly
      increased relative to baseline (1.0+/-0.3 mm, 0+/-0 mm, and 0.7+/-0.2 mm,
      respectively) and pulmonary vein lumen diameter was significantly decreased
      (5.0+/-1.4 mm versus 6.9+/-2.2 mm). Similar findings were made at the 1 week
      followup interval. At 4, 8 and 12 week followup intervals, thicknesses and lumen
      diameter were not significantly different from baseline. At post-mortem
      examination, direct measurements of wall thickness were significantly correlated
      with echocardiographic measurements. Histologic analysis demonstrated edema to be
      the cause of the early wall thickness and lumen diameter changes. Ablation
      lesions were transmural in the right atria of all animals; in some animals,
      lesion formation was also observed in the pulmonary vein wall. CONCLUSIONS:
      Cardiac edema resulting from right atrial linear ablation results in swelling of
      atrial and contiguous right pulmonary vein walls, as well as the interposed
      extracardiac interstitial space. These changes are associated with a decrease in
      pulmonary vein lumen diameter. Swelling evolves rapidly and resolves within 4
      weeks.

PMID- 11342753
TI  - P wave polarity during pacing in pulmonary veins.
AB  - INTRODUCTION: Recent studies have demonstrated that premature depolarizations
      that trigger atrial fibrillation often arise in pulmonary veins. The purpose of
      this study was to evaluate whether P wave polarity is helpful in distinguishing
      which of the 4 pulmonary veins is the site of origin of a premature
      depolarization. METHODS AND RESULTS: In 28 patients without structural heart
      disease who underwent focal ablation of paroxysmal atrial fibrillation, P wave
      polarity on a 12-lead electrocardiogram (ECG) was analyzed during sinus rhythm,
      and during pacing at a cycle length of 500--600 ms in the high right atrium and
      within each of the 4 pulmonary veins. P waves were categorized as positive,
      negative, biphasic or isoelectric. A negative or biphasic P wave in lead I
      (sensitivity 85 %, specificity 71 %) or a positive P wave in V1 (sensitivity 85
      %, specificity 89 %) were helpful in predicting a pulmonary venous site of origin
      as opposed to a right atrial site of origin. A positive P wave in lead II and III
      distinguished superior from inferior pulmonary veins (sensitivity 90 %,
      specificity 84 %). The sensitivity and specificity of negative or biphasic P
      waves in lead aVL in distinguishing a left from right pulmonary vein site of
      origin were 94 % and 42 %, respectively. CONCLUSIONS: Analysis of P waves
      polarity may be helpful in localizing the pulmonary vein that is the site of
      origin of a premature depolarization. Among the 12 ECG leads, I, II, III, aVL,
      and V1 are the most helpful in regionalizing premature depolarizations arising in
      the pulmonary veins.

PMID- 11342754
TI  - Bundle branch reentry tachycardia: why is the HV interval often longer than in
      sinus rhythm? The critical role of anisotropic conduction.

PMID- 11342755
TI  - Ultrasound-assisted cannulation of the right internal jugular vein during
      electrophysiologic studies in children.
AB  - Percutaneous access of the right internal jugular vein for coronary sinus
      cannulation in pediatric patients undergoing electrophysiologic studies may be
      technically difficult. We report the use of an ultrasound-guided technique for
      obtaining jugular venous access. Forty-five pediatric patients who underwent
      electrophysiologic study were analyzed. Access was obtained in 100 % of the
      patients using this technique with no major complications. Ultrasound guidance
      for access of the internal jugular vein for coronary sinus cannulation during
      electrophysiologic studies in pediatric patients, may increase the success rate
      and prevent the development of complications.

PMID- 11342756
TI  - Prognostic value of heart rate variability in time domain analysis in congestive
      heart failure.
AB  - AIMS: Analysis of heart rate variability is a noninvasive tool that allows to
      study autonomic control of the heart. Several studies have shown disturbed heart
      rate variability in patients with chronic heart failure (CHF). We sought to
      assess the prognostic value of time domain measures of heart rate variability in
      CHF. METHODS AND RESULTS: We prospectively enrolled 190 patients with CHF in
      sinus rhythm, mean age 61+/-12 years, 109 (57.4 %) in NYHA class II and 81 (42.6
      %) in class III or IV, mean cardiothoracic ratio 57.6+/-6.4 % and mean left
      ventricular ejection fraction 28.2+/-8.8 %, 85 (45 %) with ischemic and 105 (55
      %) with idiopathic dilated cardiomyopathy. Time domain measures of heart rate
      variability were obtained from 24 h Holter ECG recordings. During follow-up (22+/
      18 months), 55 patients died. In multivariate analysis, independent predictors
      for all-cause mortality were: ischemic heart disease, cardiothoracic ratio > or
      =60 % and standard deviation of all normal RR intervals <67 ms (RR=2.5, 95 % CI
      1.5--4.2). CONCLUSIONS: Depressed heart rate variability has independent
      prognostic value in patients with CHF.

PMID- 11342757
TI  - Incidence and management of prolonged charge times in the Medtronic model 7219
      implantable cardioverter defibrillator.
AB  - The Medtronic Jewel PCD model 7219, introduced in 1994, was the first downsized,
      pectoral implantable cardioverter defibrillator (ICD), and many of these units
      are approaching or have reached the elective replacement indicator (ERI). Unlike
      later Medtronic ICDs and most other ICDs, in which ERI is defined by battery
      voltage, the ERI in the model 7219 series is defined when either the capacitor
      charge time to full output is repeatedly> or =14.5 s or when battery voltage is<
      or =4.91 V. In this study we examined which of the two ERI criteria was met first
      in patients with this device model. We also assessed the effects of manual
      dumping and recharging and of increasing the automatic capacitor reformation
      frequency on prolonged charge times. In 16 patients with follow-up <2 years, 15
      reached the charge time ERI before battery voltage ERI. Manual dumping and
      recharging led to spuriously low charge times due to residual charge at the start
      of recharging, and increasing the automatic capacitor reformation frequency to
      once a month did not decrease prolonged charge times. Because of persistently
      prolonged charge times, 15 patients had generator changes. None of these patients
      had reached battery voltage ERI (battery voltage at time of explantation 5.06+/
      0.06 V). Thus in this early pectoral device, prolonged charge times occur
      commonly before battery voltage ERI is reached. Whether prolonged charge times
      will have an impact on device longevity in later model ICDs is unknown.

PMID- 11342758
TI  - Radiofrequency catheter ablation of posteroseptal accessory pathways--results of
      a step-by-step ablation approach.
AB  - INTRODUCTION: Transcatheter radiofrequency ablation of posteroseptal accessory
      pathways (AP) is challenging. A number of different interventional approaches
      have been suggested by different groups. The selection of the initial approach is
      crucial in order to reduce radiation exposure and the number of unsuccessful
      lesions applied. We present our ablation technique as guided by a simplified
      electrocardiographic analysis of the delta wave polarity and the
      electrophysiologic mapping results. METHODS AND RESULTS: Out of 35 manifest APs
      encountered in the right (n=17) or the left posteroseptum (n=18) in 35 patients,
      34 were successfully ablated. Despite their left sided location, 7 of the 18
      "left" sided APs were ablated after switching from an initial arterial to a
      venous approach looking for an appropriate target site in the right posteroseptal
      space or within the coronary sinus network. The other 11 left sided APs were
      ablated in the mitral ring, on 2 occasions, on their atrial aspect through a
      retrograde transmitral approach. On the contrary, 16 of the 17 "right" sided APs
      were successfully ablated exclusively through a venous approach. Fourteen of
      these were ablated in the right posteroseptum, in 2 cases, only after reaching
      their ventricular aspect. Two right sided APs were interrupted in the coronary
      sinus os and the middle cardiac vein respectively. CONCLUSION: It appears that
      even though the electrocardiographic and electrophysiologic location of the AP in
      the posteroseptal space helps select the appropriate initial approach, it does
      not always guarantee a successful ablation procedure in the expected site of the
      corresponding atrioventricular ring. Not uncommonly, it will be necessary to look
      after intermediate target sites within the coronary sinus to improve the overall
      ablation success rate.

PMID- 11342759
TI  - Echocardiographic transponder-guided catheter ablation feasibility and accuracy.
AB  - BACKGROUND: The utility of echocardiography for catheter guidance during
      percutaneous endocardial ablation is increasingly apparent. However, the
      technique is currently imperfect due to limitations in discerning the ablation
      electrode from other parts of the catheter shaft. PURPOSE: To examine the
      feasibility and accuracy of echocardiography-guided ablation using commercial
      ablation catheters fitted with a transponder to improve localization of the
      ablation electrode. METHODS: Fifteen healthy pigs and five pigs with chronic
      anterior myocardial infarction were studied. In healthy animals,
      echocardiographically distinct endocardial sites in right and left cardiac
      chambers were targeted for ablation. In infarcted animals, the left ventricular
      infarction border zone was targeted. Both intracardiac (ICE; 12.5 megahertz and 5
      megahertz) and transesophageal echocardiographic (TEE) techniques were utilized.
      RESULTS: In healthy animals, transponder-guided ablation was feasible with each
      of the echocardiographic techniques. Accuracy was 82 % (45 of 55 lesions) with
      ICE-12.5 MHz, 87 % (27 of 31 lesions) with ICE-5 MHz, and 81 % (22 of 27 lesions)
      with TEE. In infarcted animals, the accuracy was 38 % (3 of 8 lesions) for ICE-5
      MHz and 38 % (3 of 8 lesions) for TEE. Errant lesions in healthy animals were
      observed in earlier experiments, due to operator misinterpretation of the plane
      of imaging. Errant lesions in infarcted animals were observed throughout the
      experimental series, and may have been due to a variable relationship between
      echocardiographic and histologic infarction border zones. CONCLUSIONS:
      Echocardiographic transponder-guided catheter ablation is feasible. Accuracy for
      normal endocardial targets was excellent, less so for chronic infarction border.

PMID- 11342760
TI  - Catheter ablation of idiopathic left ventricular tachycardia with multiple
      breakthrough sites guided by an electroanatomical mapping system.
AB  - Idiopathic ventricular tachycardia (VT) has been considered to be amenable to
      radiofrequency catheter ablation guided by Purkinje potentials. However, there
      appear to be various types of reentrant circuits associated with this VT deduced
      from the results of the successful radiofrequency catheter ablation cases. We
      describe in this report a patient with idiopathic left ventricular tachycardia
      which was electrically inducible and verapamil sensitive. Multiple earliest
      ventricular activation sites during tachycardia were detected with
      electroanatomical mapping using the CARTO system. Multiple applications at these
      sites failed to eliminate the VT. The earliest Purkinje potential was recorded at
      least 1.5 cm away from the earliest ventricular activation sites, and the
      radiofrequency current application at this site resulted in the complete
      abolition of this VT. The reentrant circuit of this tachycardia seemed to have
      multiple breakthrough sites to the ventricular myocardium, which were distant
      from the requisite part of the reentrant circuit of this VT involving the
      Purkinje fiber network conduction system.

PMID- 11342761
TI  - Catheter ablation of idiopathic ventricular tachycardia: pathophysiological
      insights and electroanatomical mapping.

PMID- 11342762
TI  - Entrapment of a guide wire by the Chiari network in a patient with ablated
      idiopathic ventricular tachycardia.
AB  - Using a guide wire before insertion of a sheath is a common procedure with
      infrequent complications. We report an unusual case of a guide wire having been
      entrapped by the Chiari network prior to an intended radiofrequency ablation
      procedure, and which could be observed using intracardiac echocardiography. Using
      transthoracic echocardiography prior to ablation, this patient had been shown to
      have a relatively large Chiari network. We caution against using a long guide
      wire in patients with a large Chiari network.

PMID- 11342763
TI  - Images in cardiac pacing and electrophysiology. Augustin Castellanos.

PMID- 11342765
TI  - The world of pacing and electrophysiology. EP2001, symposium at the American
      College of Cardiology, Orlando, Florida, March 18, 2001.

PMID- 11342766
TI  - Ovarian mucinous carcinoids including some with a carcinomatous component: a
      report of 17 cases.
AB  - Only rare primary mucinous (goblet cell) carcinoids of the ovary have been
      reported, and their clinicopathologic features have not been well delineated. The
      authors studied 17 examples from patients 14 to 74 years of age. The clinical
      presentations were similar to those of ovarian neoplasms in general. The tumors
      ranged from 0.8 to 30 cm in diameter. In six cases the tumor was in the wall of a
      mature cystic teratoma, appearing grossly as solid nodules or areas of thickening
      in four of them, six tumors were entirely solid, and five were solid associated
      with other types of cystic tumor. The tumors were divided into three groups on
      the basis of their microscopic features. Six neoplasms, designated "well
      differentiated," were composed of small glands, many of which floated in pools of
      mucin. The glands were lined by goblet cells and columnar cells, some of which
      were of neuroendocrine type. Three tumors, designated "atypical," were
      characterized by crowded glands, some of which were confluent, small islands with
      a cribriform pattern, and scattered microcystic glands. The glands were lined by
      cuboidal to columnar cells, some of them neuroendocrine, admixed with goblet
      cells. Eight tumors, designated "carcinoma arising in mucinous carcinoid,"
      contained islands and larger nodules of tumor cells, or closely packed glands, as
      well as single cells, mainly of the signet ring cell type. Most of the cells were
      devoid of mucin and were severely atypical with marked mitotic activity. Necrosis
      was present in all eight tumors. Seven of the eight tumors with a carcinomatous
      component contained at least minor foci of well-differentiated mucinous
      carcinoid; the eighth contained only foci of atypical mucinous carcinoid. The
      neuroendocrine nature of a variable proportion of the cells in all three groups
      was demonstrated by staining for neuroendocrine markers. The mucinous nature of
      other cells was confirmed by mucicarmine or Alcian blue stains. The ovary
      contained an intrinsic component of trabecular and insular carcinoid, and of
      strumal carcinoid in one case each, an adjacent mature cystic teratoma in six
      cases, mucinous cystadenocarcinoma in three cases, and borderline mucinous cystic
      tumor, borderline Brenner tumor, and epidermoid cyst in one case each. Fifteen
      tumors were stage I, one was stage II, and one was stage III. The last two tumors
      had a carcinomatous component. Follow-up data were available for 15 patients; 12
      were alive and free of tumor 2.3 to 14 years (average, 4.7 years) after the
      ovarian tumor was excised. One patient, whose tumor had a carcinomatous
      component, died 3 years postoperatively of unrelated causes. Two patients, both
      of whom had a carcinomatous component in their tumor, died 9 and 12 months
      postoperatively. Primary mucinous carcinoids must be distinguished from
      metastatic mucinous carcinoid tumors from the appendix or elsewhere. Features
      supporting an ovarian origin are the additional presence in the specimen of
      teratoma or an ovarian surface epithelial tumor, an absence of blood vessel or
      lymphatic space invasion, and confinement to a single ovary. Similar features
      help to distinguish mucinous carcinoids from Krukenberg tumors. Mucinous
      carcinoids should also be distinguished from strumal carcinoids, which can
      contain mucinous glands, and insular carcinoid tumors that arise rarely in the
      wall of a mucinous cystic neoplasm. Although the number of cases in this series
      is small, the follow-up data suggest that the degree of differentiation,
      particularly the presence of frank carcinoma, is an important prognostic factor.

PMID- 11342767
TI  - Phenotypic characteristics of a distinctive multilayered epithelium suggests that
      it is a precursor in the development of Barrett's esophagus.
AB  - A distinctive type of multilayered epithelium (ME) has been described at the neo
      squamocolumnar junction and within columnar mucosa in patients with Barrett's
      esophagus (BE). This epithelium has morphologic and ultrastructural features of
      both squamous and columnar epithelium. Multilayered epithelium may represent an
      early or intermediate stage of columnar metaplasia; therefore, we performed this
      study to determine the morphologic and biologic characteristics of this
      epithelium and to gain insight into its derivation. Esophageal mucosal biopsies
      containing ME from 17 patients with BE were evaluated morphologically, stained
      with a variety of mucin histochemical stains; and also immunostained with
      antibodies against cytokeratins (CK) 13 (squamous epithelium marker); 14 (basal
      squamous epithelium marker) 7, 8/18, 19, and 20 (columnar epithelium markers),
      MIB-1 (proliferation marker); villin (intestinal brush border protein); and
      TGFalpha, EGFR, pS2, and hSP (enteric proliferation/differentiation regulatory
      peptides). The results were compared with normal esophageal squamous epithelium,
      normal gastric cardia epithelium, specialized-type intestinal epithelium (BE),
      and esophageal mucosal and submucosal gland duct epithelium. Multilayered
      epithelium expressed a pattern of mucin production (neutral mucin, sialomucin,
      and sulfomucin in 88%, 100%, and 71% of cases, respectively) and cytokeratin
      expression (CK 13 and 19 in the basal "squamoid" cells, CK 7, 8/18, 19, and 20 in
      the superficial "columnar" cells) similar to that of columnar epithelium in BE,
      and showed a high capacity for cellular proliferation (Ki-67-positive in 88% of
      cases) and differentiation (TGFalpha, EGFR, pS2 and villin-positive in 100%,
      100%, 93%, and 66% of cases, respectively). The mucosal gland duct epithelium
      showed a similar phenotypic pattern and, in one case, was seen to give rise to ME
      at the surface of the mucosa. These data provide evidence in support of the
      hypothesis that ME represents an early or intermediate stage in the development
      of esophageal columnar metaplasia (BE). The mucosal gland duct epithelium may
      contain progenitor cells that can give rise to ME.

PMID- 11342768
TI  - Pancreatic intraepithelial neoplasia: a new nomenclature and classification
      system for pancreatic duct lesions.
AB  - Proliferative epithelial lesions in the smaller caliber pancreatic ducts and
      ductules have been the subject of numerous morphologic, clinical, and genetic
      studies; however, a standard nomenclature and diagnostic criteria for classifying
      these lesion have not been established. To evaluate the uniformity of existing
      systems for grading duct lesions in the pancreas, 35 microscopic slides with 35
      representative duct lesions were sent to eight expert pathologists from the
      United States, Canada, and Europe. Kappa values for interobserver agreement could
      not be calculated initially because more than 70 different diagnostic terms were
      used by the eight pathologists. In several cases, the diagnoses rendered for a
      single duct lesion ranged from "hyperplasia," to "metaplasia," to "dysplasia," to
      "carcinoma in situ." This review therefore demonstrated the need for a standard
      nomenclature and classification system. Subsequently, during a working group
      meeting, the pathologists agreed to adopt a single standard system. The
      terminology pancreatic intraepithelial neoplasia (or PanIN) was selected, and
      diagnostic criteria for each grade of PanIN were established
      (http://pathology.jhu.edu/pancreas_panin). This new system was then evaluated by
      having the eight pathologists rereview the original 35 cases. Only seven
      different diagnoses were rendered, and kappa values of 0.43, 0.14, and 0.42 were
      obtained for PanINs 1, 2, and 3 respectively. Cases assigned other diagnoses
      (e.g., squamous metaplasia) collectively had a kappa value of 0.41. These results
      show both the potential of the classification system, and also the difficulty of
      classifying these lesions even with a consistent nomenclature. However, even when
      there is lack of consensus, having a restricted set of descriptions and terms
      allows a better understanding of the reasons for disagreement. It is suggested
      that we adopt and apply this system uniformly, with continued study of its
      reliability and use, and possibly further refinement. The acceptance of a
      standard classification system will facilitate the study of pancreatic duct
      lesions, and will lead ultimately to a better understanding of their biologic
      importance.

PMID- 11342769
TI  - Dendritic cell neurofibroma with pseudorosettes: a report of 18 cases of a
      distinct and hitherto unrecognized neurofibroma variant.
AB  - The authors present 18 cases of a hitherto unrecognized variant of cutaneous
      neurofibroma. The tumors presented in adults (10 occurred in men and eight
      occurred in women) as a solitary, well-circumscribed, superficial lesion located
      in the dermis measuring 3 to 17 mm (mean size, 6.2 mm). The tumors formed oval
      shaped masses that ran perpendicular to the epidermis. In the deep part of the
      tumor there was multinodular arrangement with two types of cells: Type I cells
      were small, dark, lymphocyte-like cells with a slightly irregular nucleus and
      inconspicuous cytoplasm. Type II cells were larger, with pale-staining vesicular
      nuclei, with frequent invaginations and intranuclear inclusions, and had copious
      clear eosinophilic cytoplasm that formed a stellate growth pattern, which was
      poorly visible on hematoxylin and eosin staining. Type I cells were grouped
      concentrically around type II cells and formed pseudorosettes. Most of the type I
      and type II cells were S-100 protein and CD57 positive, and various proportions
      of both cell types were CD56 and PGP9.5 positive. All cells were chromogranin A,
      synaptophysin, glial fibrillary acidic protein, cytokeratins, CD1a, CD21, CD31,
      alpha-smooth muscle actin, muscle-specific actin, desmin, and HMB-45 negative.
      CD34 stained intralesional fibroblasts. Antibody to epithelial membrane antigen
      stained only the perineurium around the tumor masses, suggesting that the tumors
      arose inside the nerve sheath. No signs of neurosecretory granules were present
      at ultrastructural level. None of the lesions recurred and none metastasized over
      a mean follow-up of 8.1 years.

PMID- 11342770
TI  - Small cell carcinoma of the gallbladder: a clinicopathologic,
      immunohistochemical, and molecular pathology study of 12 cases.
AB  - Small cell carcinomas of the gallbladder are unusual neoplasms that have been
      characterized only recently. The authors describe the clinical, histopathologic,
      immunohistochemical, and molecular features of 12 small cell carcinomas of the
      gallbladder. The mean age at diagnosis was 69 years, and the male-to-female ratio
      was 5:7. The neoplasms had an average size of 3 cm, and 90% showed invasion of
      the muscularis propria and perimuscular connective tissue. Seventy-five percent
      of the carcinomas had metastasized or extended locally beyond the gallbladder at
      surgery. Survival was uniformly poor, with a mean survival of 10.7 months (range,
      3-25 months). Half the small cell carcinomas were combined with other neoplasms.
      Four had foci of adenocarcinoma, one contained areas of squamous differentiation,
      and another had a component of carcinosarcoma. Immunohistochemical analysis
      showed focal reactivity for chromogranin (six of six cases), neuron-specific
      enolase (six of six cases), and Leu-7 (three of three cases). The molecular
      changes in small cell carcinomas were similar to those of adenocarcinomas
      occurring at this site, with a high frequency of p53 (75%) and p16INK4a (33%)
      abnormalities, and a low frequency of deleted in pancreatic carcinoma-4
      inactivation (0%) and K-ras codon 12 mutations (17%). In contrast to pulmonary
      small cell carcinomas, p16INK4a function appears to be abrogated more frequently
      in these carcinomas.

PMID- 11342771
TI  - Clear cell endocrine pancreatic tumor mimicking renal cell carcinoma: a
      distinctive neoplasm of von Hippel-Lindau disease.
AB  - The dominantly inherited von Hippel-Lindau disease is characterized by clear cell
      neoplasms in various organs including the kidney and pancreas. Determination of
      primary versus metastatic lesion in this setting can be a diagnostic dilemma. The
      authors present five cases of clear cell endocrine pancreatic tumor (EPT) closely
      mimicking renal cell carcinomas in five patients with a family history or
      histologic evidence of von Hippel-Lindau disease. In fact, two of these tumors
      were confused with metastatic renal cell carcinoma by fine-needle aspiration. All
      five tumors had a component of clear cells arranged in nests, cords, and tubules
      with central hemorrhage separated by thin-wall vessels resembling renal cell
      carcinoma. However, these tumors also exhibited cords and festoons and a gyriform
      pattern suggestive of an endocrine neoplasm, and expressed chromogranin and
      synaptophysin. Vascular invasion was identified in four tumors, one of which
      metastasized. The concurrent primary renal cell carcinomas and the multicentric
      microcystic adenomas found in three patients did not show reactivity for the
      neuroendocrine markers. Focal clear cell change was noted in only one of 29
      endocrine pancreatic tumors arising in patients without von Hippel-Lindau
      disease. Eleven metastatic renal cell carcinomas in the pancreas did not show
      immunoreactivity with the endocrine markers. Clear cell EPTs closely mimicking
      renal cell carcinoma are distinctive neoplasms of von Hippel-Lindau disease. In
      contrast to clear cell EPT, metastatic renal cell carcinoma does not express
      neuroendocrine markers and lacks neurosecretory granules by electron microscopy.
      Von Hippel-Lindau disease should be strongly suspected in patients with renal
      cell carcinoma, clear cell EPT, and multifocal microcystic serous adenomas.

PMID- 11342773
TI  - Prostatic foamy gland carcinoma with aggressive behavior: clinicopathologic,
      immunohistochemical, and ultrastructural analysis.
AB  - Foamy gland carcinoma is a recently described histologic variant of prostatic
      adenocarcinoma characterized by abundant foamy cytoplasm and minimal cytologic
      atypia. The biologic behavior and biochemical nature of the foamy adenocarcinoma
      cells are unknown. Six cases of prostatic adenocarcinoma with marked foamy
      appearance were identified from radical prostatectomies. Clinicopathologic,
      histochemical, immunohistochemical, and ultrastructural analyses were conducted.
      The patients ranged in age from 50 to 73 years (mean age, 65 years) with
      preoperative serum prostate-specific antigen levels ranging from 2.7 to 37.5
      ng/mL (mean, 15.2 ng/mL). All six cases were bilateral high-volume tumors. Five
      of six patients had high-grade tumors with extraprostatic extension. The foamy
      tumor cells were negative for mucin and lipid stains, but were positive for
      colloidal iron and Alcian blue stain. Ultrastructurally, the foamy cells
      displayed numerous intracytoplasmic vesicles and numerous polyribosomes. The
      authors conclude that the foamy appearance of these tumor cells is the result of
      the presence of numerous intracytoplasmic vesicles, and not the result of the
      presence of lipid or neutral mucin. This study illustrates that foamy gland
      carcinoma is a distinctive histologic variant of prostatic adenocarcinoma and is
      often associated with an aggressive behavior despite its deceivingly benign
      histologic appearance.

PMID- 11342772
TI  - Calretinin and other mesothelioma markers in synovial sarcoma: analysis of
      antigenic similarities and differences with malignant mesothelioma.
AB  - Synovial sarcoma (SS) is a mesenchymal neoplasm that typically shows epithelial
      differentiation. SS commonly metastasizes to lung and pleura, and has also been
      reported as the primary in these locations. The histologic distinction of SS from
      mesothelioma may be difficult because of the combination of epithelioid and
      spindle cells, potentially shared locations, and antigenic expression. In this
      study the authors examined 103 well-documented SSs including 41 biphasic, 44
      monophasic, and 18 poorly differentiated SSs in comparison with 23 epithelioid
      and seven sarcomatous mesotheliomas. Most biphasic SSs (29 of 41, 71%) had fields
      or foci of calretinin-positive tumor cells. The spindle cell components were more
      often positive (55%), whereas 14% of tumors had positive epithelial cells. The
      monophasic and poorly differentiated SSs commonly had foci of calretinin-positive
      cells (in 52% and 56% of cases respectively). In comparison, all 23 epithelioid
      mesotheliomas (EM) were extensively calretinin positive and seven sarcomatoid
      mesotheliomas were variably calretinin positive. HBME-1 positivity was similarly
      detected in biphasic SS and EM (100% and 87% respectively). Among the other
      sarcomas, two of 15 malignant peripheral nerve sheath tumors were focally
      calretinin positive, whereas 16 epithelioid sarcomas, 20 leiomyosarcomas, 20
      gastrointestinal stromal tumors, and 20 angiosarcomas were negative. Biphasic SSs
      differed from mesotheliomas by their more common BerEp4 positivity (90%) whereas
      EMs showed focal reactivity in 13% cases. Marked CD15 reactivity was rare in
      both. Wilms tumor protein-1 (WT1) was not detected in SS, but was present in 12
      of 17 EMs. CD141 was rare in SS, limited to spindle cell components, whereas EMs
      typically showed prominent membrane staining in epithelial cells. Simple
      epithelial keratins were present in all epithelial cells of biphasic SS and
      mesothelioma (keratin 7[K7], K19), but were only focal in monophasic and poorly
      differentiated SS. Biphasic SSs were extensively K14 positive (89% of cases),
      whereas epithelial and sarcomatoid mesotheliomas typically showed only scattered
      positive cells. The potentially shared calretinin patterns in SS and mesothelioma
      require the use of other markers. The discriminating features include extensive
      BerEp4 positivity, rarity of CD141, and lack of WT1 in SS. Global expression of
      K7 and K19 in mesotheliomas versus focal expression in monophasic and poorly
      differentiated SSs, and differential patterns of K14 expression may also be
      helpful.

PMID- 11342774
TI  - Human herpesvirus-8 genes are expressed in pulmonary inflammatory myofibroblastic
      tumor (inflammatory pseudotumor).
AB  - The presence of human herpesvirus-8 DNA sequences, as well as an overexpression
      of human interleukin-6 and human cyclin D1 in myofibroblastic cells of
      inflammatory myofibroblastic tumor (inflammatory pseudotumor), has recently been
      reported. We describe the pattern of human herpesvirus-8 gene expression in five
      cases of pulmonary inflammatory myofibroblastic tumor. Reverse transcriptase
      polymerase chain reaction (RT-PCR), with several positive and negative controls,
      was performed to detect mRNA of 11 open reading frames encoded by human
      herpesvirus-8 in lytic and latent stages of viral replicative cycle. We found
      molecular transcripts from ORF16, ORFK13, and ORF72 in the five cases and from
      ORFK2 in four of five neoplasms. The corresponding encoded proteins were human
      homologous oncoproteins (viral cyclin-D), inflammatory cytokines (viral IL-6),
      and inhibitors of apoptotic pathways (viral FLIP and viral Bcl-2), mostly
      expressed in a latent viral replicative stage. The rest of open reading frames
      examined included mainly lytic-associated genes and showed no expression. The
      spectrum of expressed viral genes is not the same as can be observed in Kaposi's
      sarcoma or multicentric Castleman's disease, suggesting that human herpesvirus-8
      plays a different role in the pathogenesis of its associated diseases. These
      differences may be related to either cell-specific or immunologic host factors.

PMID- 11342775
TI  - Pulmonary Langerhans' cell histiocytosis: molecular analysis of clonality.
AB  - Pulmonary Langerhans' cell histiocytosis (LCH) is a form of Langerhans' cell
      disease that primarily affects smokers in the third to fifth decade.
      Extrapulmonary manifestations are rare. Its clinical course is typically
      characterized by stabilization or regression of bilateral micronodular
      infiltrates seen on chest radiographs; progression to honeycomb fibrosis is rare.
      Because the clinical course of pulmonary LCH is distinct from systemic multiorgan
      LCH, currently thought to be a clonal proliferative disorder, we examined the X
      linked polymorphic human androgen receptor assay (HUMARA) locus to assess
      clonality in female patients with one or more discrete LCH cell nodules in open
      lung biopsies. Langerhans' cells (LCH cells) were excised from formalin-fixed,
      paraffin-embedded tissue by microdissection to assure a relatively pure cellular
      population, and studies for differential methylation patterns at the HUMARA locus
      were performed. Twenty-four nodules in 13 patients were evaluated. Seven (29%)
      were clonal and 17 (71%) were nonclonal. Of six cases with multiple discrete
      nodules, three (50%) showed a nonclonal LCH cell population. In one biopsy with
      five nodules, two nodules were clonal with one allele inactivated, one nodule was
      clonal with the other allele inactivated, and two nodules were nonclonal. In
      contrast to systemic LCH, pulmonary LCH appears to be primarily a reactive
      process in which nonlethal, nonmalignant clonal evolution of LCH cells may arise
      in the setting of nonclonal LCH cell hyperplasia. Cigarette smoking may be the
      stimulus for pulmonary LCH in contrast to other forms of LCH.

PMID- 11342776
TI  - Upper gastrointestinal tract injury in patients receiving kayexalate (sodium
      polystyrene sulfonate) in sorbitol: clinical, endoscopic, and histopathologic
      findings.
AB  - Kayexalate (sodium polystyrene sulfonate) in sorbitol has been demonstrated to
      cause colonic necrosis in a subset of uremic patients who are administered the
      cation exchange resin for treatment of hyperkalemia. Upper gastrointestinal
      damage associated with Kayexalate in sorbitol is reported far less frequently,
      and the clinicopathologic spectrum of disease in cases with upper
      gastrointestinal damage has not been investigated previously. The authors studied
      the clinical, endoscopic, and histologic features of 11 patients with Kayexalate
      crystals in biopsies from the esophagus (n = 7), stomach (n = 6), and duodenum (n
      = 2). The endoscopic appearance was markedly abnormal in all 11 patients. The
      effects of the medication closely mimicked other endoscopic and radiologic
      diagnoses in three cases, including esophageal carcinoma, Candidal esophagitis,
      and gastric bezoar. Histologic and/or endoscopic evidence of mucosal injury in
      the form of an ulcer or erosion was present in nine patients (82%). In four
      patients with mucosal injury, no other etiology apart from Kayexalate in sorbitol
      could be identified. In comparison with a cohort of patients with Kayexalate
      crystals in lower gastrointestinal specimens identified during the same period
      (11 patients) the frequency of associated mucosal damage was not significantly
      different (55%, p = 0.19), but no patient with upper gastrointestinal Kayexalate
      required surgical resection or died as a result of Kayexalate-induced mucosal
      injury. The results of this study provide evidence that Kayexalate in sorbitol
      can induce damage to the upper gastrointestinal tract. Recognition of Kayexalate
      crystals in histologic sections as a marker for sorbitol-induced mucosal damage
      may aid in establishing the correct diagnosis for clinically or endoscopically
      misleading lesions.

PMID- 11342777
TI  - Gardner-associated fibromas (GAF) in young patients: a distinct fibrous lesion
      that identifies unsuspected Gardner syndrome and risk for fibromatosis.
AB  - Gardner syndrome (GS), caused by mutations in the adenomatous polyposis coli
      (APC) gene, is characterized by polyposis coli, osteomas, and various soft-tissue
      tumors. If undetected or untreated, virtually all patients develop colonic
      carcinoma at a young age. Early detection, while essential, can be difficult
      because of attenuated phenotypes or spontaneous mutations. We present the
      clinicopathologic features of 11 identical fibromatous lesions that we have
      termed Gardner-associated fibroma (GAF), which not only appear to be a part of
      the spectrum of lesions associated with GS but, in some cases, represent the
      sentinel event leading to its detection. The GAFs occurred in 11 patients (5 boys
      and 6 girls; age range, 3 months-14 years), were solitary (n = 7) or multiple (n
      = 4), and occurred in the superficial and deep soft tissues of the paraspinal
      region (n = 7), back (n = 3), face (n = 2), scalp (n = 2), chest wall (n = 2),
      thigh (n = 1), neck (n = 1), and flank (n = 1). Histologically, GAFs resemble
      nuchal-type fibromas (NFs), consisting of thick, haphazardly arranged collagen
      bundles between which are found occasional bland fibroblasts, and having margins
      that frequently engulf surrounding structures including adjacent fat, muscle and
      nerves. After surgical excision, four patients developed recurrences that were
      classic desmoid fibromatoses (DFs). In one patient with multiple GAFs, one lesion
      had the features of GAF and DF in the absence of surgical trauma. A family
      history of GS or polyposis (n = 6) or DF (n = 1) was known at the time of surgery
      in seven patients. In three patients, the diagnosis of GAF resulted in the
      diagnosis of unsuspected APC in older family members, with the detection of an
      occult colonic adenocarcinoma in one parent. In the family of the remaining
      patient, no stigmata of GS were present. Genetic analysis of this child was
      performed to investigate the presence of a spontaneous (new) mutation; however,
      no abnormalities were detected. The significance of GAF is that it serves as a
      sentinel event for identifying GS kindreds, including those with a high risk for
      the development of DF, and it may potentially identify children with spontaneous
      mutations of the APC gene. Because NFs and GAFs resemble one another, we suggest
      that a subset of NF occurring in multiple sites, unusual locations, or children
      may be GAF.

PMID- 11342778
TI  - Bizarre epithelial atypia of the sinonasal tract after chemotherapy.
AB  - Certain chemotherapeutic agents can induce bizarre epithelial atypia. The lower
      respiratory tract is a frequently targeted site, but similar changes have not
      been described adequately in the sinonasal tract. Unfamiliarity with these
      changes could potentially cause confusion with an infectious or neoplastic
      process. All biopsies of the sinonasal tract at The Johns Hopkins Hospital were
      reviewed prospectively over a 54-month period. Eleven cases with bizarre atypia
      of the respiratory epithelium formed the basis of this study. The medical records
      of these patients were reviewed. The specimens were from 11 patients who had
      previously undergone chemotherapy and bone marrow transplantation for acute
      myelocytic leukemia (n = 5), multiple myeloma (n = 3), acute lymphocytic leukemia
      (n = 2), and chronic myelocytic leukemia (n = 1). Although the chemotherapy
      regimens were highly variable, all included one or more of the alkylating agents
      (cyclophosphamide, n = 11; busulfan, n = 5; melphalan, n = 1). In all 11
      patients, biopsies were acquired to rule out invasive fungal sinusitis. The
      atypical epithelial changes included striking nuclear enlargement,
      hyperchromasia, and pleomorphism. Sometimes these changes were full thickness and
      were associated with squamous metaplasia. Two of eight cases evaluated by frozen
      section were misinterpreted initially as high-grade epithelial dysplasia. Certain
      chemotherapeutic agents can induce striking epithelial atypia in the sinonasal
      tract. These changes should not be interpreted as neoplastic in nature, a
      potential pitfall in the frozen section evaluation of a destructive nasal process
      in oncology patients.

PMID- 11342779
TI  - Primary Gleason pattern as a predictor of disease progression in gleason score 7
      prostate cancer: a multivariate analysis of 823 men treated with radical
      prostatectomy.
AB  - Gleason score (GS) is a powerful predictor of disease progression in men with
      prostate cancer (PCa). The majority of clinically localized prostate cancers,
      however, are moderately (GS5/6) or moderate to poorly (GS7) differentiated tumors
      with indeterminate prognosis. Differences in disease progression between patients
      with GS5/6 and GS7 tumors suggest the presence of any component of high-grade
      tumor (Gleason pattern [GP] 4/5) worsens prognosis markedly. Indeed, McNeal et
      al. have shown that quantification of GP4/5 provides prognostic information
      beyond the standard GS. Few investigators have analyzed whether primary and
      secondary GPs are important prognostically within GS7 PCa. All 823 whole-mount
      radical prostatectomy specimens with GS7 from a single surgeon (P.T.S.) were
      analyzed. Tumors were either 3+4 or 4+3, and primary GP was assigned by the same
      pathologist (T.M.W.). A total of 643 patients with 3+4 tumors and 180 patients
      with 4+3 tumors were studied. Statistical analysis using the log-rank test showed
      a significant difference in recurrence-free survival between patients with
      primary GP4 and those with GP3 (p <0.0001). However, in multivariate analysis
      with preoperative prostate-specific antigen, total tumor volume, surgical margin
      status, and the presence or absence of seminal vesicle involvement,
      extraprostatic extension, and lymph node metastasis, the primary GP did not
      retain independent significance (p = 0.0557). GS7 PCa is a heterogeneous group of
      tumors. In this cohort of men with GS7 tumors treated by radical retropubic
      prostatectomy, primary GP showed a significant correlation with other histologic
      and clinical predictors of disease progression; however, it was not independently
      predictive of disease progression in multivariate analysis (p = 0.76).

PMID- 11342780
TI  - Chondroblastoma-like chondroma of soft tissue: an underrecognized variant and its
      differential diagnosis.
AB  - Soft-tissue chondromas are usually composed entirely of mature hyaline cartilage.
      Infrequently, however, they may exhibit morphologic features that result in
      diagnostic difficulty. The authors report a series of eight hypercellular soft
      tissue chondromas composed of enlarged chondrocytes within a variable amount of
      chondroid matrix that often demonstrated delicate calcifications and contained
      numerous osteoclast-like multinucleated giant cells. This histologic appearance
      closely resembles that of chondroblastoma of bone. However, its extraosseous
      location, dense cellularity, and poorly formed cartilage can cause confusion with
      more aggressive chondroid neoplasms of soft tissue. The clinicopathologic
      features of these chondroblastoma-like chondromas are discussed, emphasizing the
      characteristics that facilitate their accurate identification.

PMID- 11342781
TI  - Absence of estrogen receptor-alpha expression in human ovarian clear cell
      adenocarcinoma compared with ovarian serous, endometrioid, and mucinous
      adenocarcinoma.
AB  - The mechanism that regulates growth in ovarian clear cell adenocarcinoma (CCA) is
      not well understood. A high incidence of concurrent endometriosis with CCA may
      indicate that estrogen is a growth promotor in CCA. To determine estrogen as a
      growth promotor, the authors investigated the presence or absence of estrogen
      receptor-alpha (ER-alpha), ER-beta, progesterone receptor, and dioxin receptor
      (i.e., aromatic hydrocarbon receptor) in clinically resected ovarian CCA, serous
      adenocarcinoma (SAC), endometrioid adenocarcinoma (EAC), and mucinous
      adenocarcinoma (MAC) specimens using an immunohistochemical method. Expression of
      ER-alpha and ER-beta messenger ribonucleic acid was examined by reverse
      transcription-polymerase chain reaction in three established CCA cell lines: KK,
      RMG-1, and HAC-II. None of the surgically resected CCA and CCA cell lines showed
      positive staining for ER-alpha. Conversely, 97.2% of SACs, 100% of EACs, and 70%
      of MACs showed positive nuclear staining for ER-alpha (p < 0.001). Conversely,
      positive ER-beta staining for CCA (39.3%) was similar to that of SAC (41.7%) and
      MAC (30.0%). EAC (75%) showed a higher expression of ER-beta (p < 0.02).
      Progesterone receptor was detected in only 10.7% of CCA, compared with SAC and
      EAC (SAC, 86.1%; EAC, 91.7%; p < 0.01). Aromatic hydrocarbon receptor was
      detected in all histologic types at an incidence of approximately 50% to 60%.
      Messenger ribonucleic acid of ER-alpha and ER-beta was not detected in the three
      CCA cell lines. These findings indicate biologic characteristics that distinguish
      CCA from other types of ovarian epithelial cancer.

PMID- 11342782
TI  - Clinicopathologic features and human papillomavirus dna prevalence of warty and
      squamous cell carcinoma of the penis.
AB  - Squamous cell carcinoma (SCC) accounts for 95% of penile malignant neoplasms. A
      subtype of SCC, named warty carcinoma (WC), is a morphologically distinct
      verruciform tumor with features of human papillomavirus (HPV)-related lesions.
      Descriptions of the behavior and histologic features of this tumor are scarce in
      the literature. The aim of this report is to analyze the clinicopathologic
      features and HPV deoxyribonucleic acid status in 60 SCCs and 11 WCs. The mean
      patient age was 46.5 +/- 15.9 years for WC and 52.6 +/- 12.4 years for SCC. No
      significant differences in age (p = 0.154) and clinical staging (T, p = 0.649; N,
      p = 0.497) between the two groups of tumors were found. When compared with SCCs,
      WCs exhibited less lymphatic embolization (p = 0.001), nodal metastasis (p =
      0.019), and corpora cavernosa and corpus spongiosum infiltration (p = 0.040).
      Lymph node metastases were found in 34 of 60 SCC patients (56.7%) and in two of
      11 WC patients (18.2%). No patients with WC tumors died of the disease compared
      with 19 of 60 (5-year specific survival, 66.0%) in the SCC group (p = 0.032). HPV
      deoxyribonucleic acid was more likely to be associated with WC (five of 11,
      45.5%) than SCC (16 of 60, 26.7%), although significance was not reached (p =
      0.209). The results suggest that WC is less aggressive and confers a better
      prognosis than typical SCC of the penis.

PMID- 11342783
TI  - Pulmonary apical cap: a distinctive but poorly recognized lesion in pulmonary
      surgical pathology.
AB  - Thirteen cases of pulmonary apical cap (PAC), resected for the exclusion of a
      clinical diagnosis of lung carcinoma, were reviewed, and their distinctive
      morphology was described. PAC occurred in older individuals, particularly in the
      apices of the upper lobes, and by radiographic examination appeared as spiculated
      subpleural masses ranging from 0.7 to 5.2 cm in diameter. Microscopically, these
      subpleural scars were pyramid shaped with overlying pleural adhesions and hyaline
      pleural plaques. They were characterized by a dense basophilic fibrosis of the
      pulmonary parenchyma with air spaces filled with old, mature collagen and the
      underlying elastic skeleton contracted in an accordion-like fashion with
      reduplicated curls of elastic fibers. Scar emphysema was prominent at the
      periphery of these fibrous nodules. PAC should be recognized for its unique
      histology because its appearance in the surgical pathology laboratory will likely
      increase in incidence with the evolution of more sensitive pulmonary radiographic
      studies. A chronic ischemic etiology is favored.

PMID- 11342784
TI  - Translocation t(1;3)(p36.3;q25) is a nonrandom aberration in epithelioid
      hemangioendothelioma.
AB  - The cytogenetic findings for two epithelioid hemangioendotheliomas are reported.
      An identical chromosomal translocation involving chromosomes 1 and 3
      [t(1;3)(p36.3;q25)] was detected in both cases of epithelioid
      hemangioendothelioma, possibly representing a characteristic rearrangement for
      this histopathologic entity. The presence of clonal karyotypic abnormalities
      supports a neoplastic origin for the epithelioid variant of hemangioendothelioma.
      Identification of the 1;3 translocation may be useful diagnostically. Should
      additional studies confirm these data, this could lead to the identification of
      the gene(s) central to this neoplastic process.

PMID- 11342785
TI  - Pulmonary gangliocytic paraganglioma: case report and comparative
      immunohistochemical study of related neuroendocrine neoplasms.
AB  - The authors report a case of gangliocytic paraganglioma of the lung, which has
      not yet been described in a pulmonary neoplasm. A 75-year-old man underwent right
      middle and lower lobe lobectomy. A slightly yellowish mass was located at the
      bifurcation between the lower and middle lobe bronchus, protruding into the
      truncus intermedius. The neoplastic cells were composed of three cellular
      elements: uniform endocrine cells in a Zellballen arrangement, large ganglion
      like cells within the nests of endocrine cells, and spindle-shaped cells arranged
      in streams to surround the nests. Each component exhibited the characteristic
      immunohistochemical properties, which were similar to those of the corresponding
      neuroendocrine neoplasms: Endocrine cells were positive for CAM 5.2, chromogranin
      A, and synaptophysin, like carcinoid tumor; ganglion-like cells were positive
      only for neurofilament, like ganglioneuroma; and spindle-shaped cells were
      positive for neurofilament and S-100 protein, like paraganglioma. These results
      agreed with those in gangliocytic paraganglioma of the duodenum. Pulmonary
      gangliocytic paraganglioma is similar to that in the duodenum, and is a
      hamartomatous proliferation of epithelial endocrine and neuronal cells of the
      bronchus.

PMID- 11342786
TI  - Gastric dysplasia: the Pavoda International Classification.

PMID- 11342787
TI  - Gardner syndrome.

PMID- 11342788
TI  - Epithelial sheath neuroma: a benign neoplasm?

PMID- 11342789
TI  - Economic evaluation and the treatment of end-stage renal disease.

PMID- 11342791
TI  - Tubulointerstitial renal disease.
AB  - Tubulointerstitial damage, in progressive chronic renal disease of all types,
      arises because of a complex interplay between factors in the tubular lumen,
      tubular epithelial cells, peritubular capillaries, resident and infiltrating
      interstitial cells and extracellular matrix. Particularly in proteinuric renal
      disease, tubular epithelial cells play a central role in orchestrating these
      events. In response to mediators arising systemically, in the tubular lumen or
      from other renal cells, tubular epithelial cells undergo a complex series of
      structural and functional changes and produce a bewildering number of soluble and
      fixed mediators, which in turn lead to interstitial inflammation and fibrosis.
      Knowledge of these interactions has increased exponentially over the past decade,
      and has defined a number of new targets for treatment. Both expansion and
      consolidation of this knowledge is needed to determine which of these targets
      holds the most promise for future treatment.

PMID- 11342792
TI  - Renal fibrosis: an update.
AB  - Tubulointerstitial fibrosis invariably accompanies the course of chronic renal
      failure towards end-stage renal disease. Tubular epithelial cells, the
      predominant cell type in the tubulointerstitium, are increasingly being
      recognized for playing a dominant role as mediators of renal fibrogenesis.
      Tubular epithelial cells become activated either by the glomerular ultrafiltrate
      from their apical side or by mononuclear cells from their basolateral side. They
      initiate the scarring process by secreting chemokines, which in return attract
      mononuclear cells as well as growth factors that stimulate interstitial
      fibroblasts. In later phases of renal fibrogenesis, cellular changes of tubular
      epithelial cells contribute to the chronic impairment of renal function. Whereas
      tubular epithelial cells react by proliferation or hypertrophy to initial
      stimuli, they may undergo apoptosis or transdifferentiate into fibroblasts, and
      thus contribute to tubular atrophy in later stages of progressive renal disease.
      Resident interstitial fibroblasts are also important in renal fibrogenesis, and
      recent research has demonstrated that these cells are much more heterogeneous
      than expected. Cytokines such as fibroblast growth factor type 2 and epithelial
      growth factor have been shown to be pro-fibrogenic, whereas hepatocyte growth
      factor and bone morphogenic protein type 7 may inhibit fibrogenesis. Despite
      recent progress, further research is mandatory for a better understanding and the
      development of novel therapeutic approaches.

PMID- 11342793
TI  - Proinflammatory actions of angiotensins.
AB  - Many experimental data have suggested that the renin-angiotensin system
      participates in immune and inflammatory responses. Angiotensin II is involved in
      several steps of the inflammatory process: mononuclear cells respond to
      angiotensin II stimulation (cell proliferation and chemotaxis); angiotensin II
      regulates the recruitment of proinflammatory cells into the site of injury
      (mediated by the expression of vascular permeability factors, adhesion molecules
      and chemokines by resident cells); inflammatory cells can produce angiotensin II,
      and might therefore contribute to the perpetuation of tissue damage. In this
      review, we summarize the proinflammatory properties of angiotensin II, to
      demonstrate the novel role of this vasoactive peptide as a true cytokine. We will
      show the information obtained as a result of the pharmacological blockade of the
      renin angiotensin system, which has demonstrated that this system is involved in
      immune and inflammatory diseases. In this aspect, we discuss the molecular
      mechanism of angiotensin II-induced tissue damage, as well as its contribution to
      the pathogenesis of several diseases, including atherosclerosis, hypertension and
      renal damage, showing that angiotensin II plays an active role in the
      inflammatory response of these diseases.

PMID- 11342794
TI  - Update in podocyte biology.
AB  - Knowledge of podocyte biology is growing rapidly. Podocytes are crucially
      involved in most hereditary diseases affecting the glomerulus, which all exhibit
      podocyte-specific defects, that is, foot process effacement and protein leakage.
      Efforts to understand molecular mechanisms causing these derangements are
      increasingly successful and will allow a better targeting of interventions to
      halt the progression of chronic renal disease.

PMID- 11342795
TI  - Macrophages in renal inflammation.
AB  - This review describes recent advances in macrophage biology in the context of
      renal inflammation. It highlights the importance of the activated macrophage for
      the progression and resolution of renal disease, and discusses recent and
      potential future approaches to modify macrophage function selectively within the
      kidney to activate them specifically to promote the healing of kidney disease.

PMID- 11342796
TI  - Advances in transplant immunobiology.
AB  - The present review briefly addresses the most recent knowledge acquired in the
      field of transplant immunology. A particular emphasis is placed on articles
      published during the past 12-18 months that have focused on allorecognition,
      dendritic cells and tolerance.

PMID- 11342797
TI  - Immunopathogenesis of the antiphospholipid antibody syndrome: an update.
AB  - The primary antiphospholipid antibody syndrome is characterized clinically by the
      presence of venous and arterial thrombosis, recurrent fetal loss, and
      thrombocytopenia. The presence of antiphospholipid antibodies is a central
      serologic finding in primary antiphospholipid antibody syndrome, and plays a
      critical role in diagnosis. Contrary to initial reports, it is now widely
      accepted that these autoantibodies are directed predominantly against two
      antigens: phospholipid-binding plasma protein beta2-glycoprotein I and
      prothrombin. The mechanism by which antiphospholipid antibodies cause disease is
      under vigorous investigation. It is hypothesized that antiphospholipid antibodies
      induce a procoagulant state by binding to antigens on endothelial cells and
      trophoblast cell surfaces. Indeed, beta2-glycoprotein I appears to function as a
      cofactor that facilitates this interaction. The resulting endothelial cell
      activation is associated with cell-surface expression of adhesion molecules that
      lead to monocyte adhesion - the first steps in thrombosis. Although the precise
      mechanism that mediates endothelial cell-platelet interaction have not been fully
      elucidated, platelet binding to the endothelium appears to be the next phase in
      thrombosis. Thus, the antiphospholipid antibody may be a triggering or activating
      factor in placental spiral artery thrombosis and subsequent placental infarction.
      More recently, a role for annexin V has emerged. Studies suggest that thrombosis
      in the antiphospholipid syndrome may be due to disruption of the annexin shield
      by antiphospholipid (and cofactor) antibodies, which results in the increased
      exposure of trophoblasts and endothelial cells to thrombogenic phospholipids.

PMID- 11342798
TI  - Dietary modification and changes in blood pressure.
AB  - Several recently published clinical trials and epidemiological studies have added
      significant new data to our understanding of the impact of dietary modifications
      on blood pressure. Such studies confirm the blood pressure-lowering effects of
      sodium restriction, the consumption of diets that are low in fat and enriched in
      fruits and vegetables, and the sustained effects of weight reduction. This
      reaffirms the role of lifestyle modifications as both preventative and adjunctive
      means to lower blood pressure.

PMID- 11342799
TI  - Non-invasive assessments of cardiovascular disease in patients with renal
      failure.
AB  - Vascular calcification is common in patients with chronic renal failure, and it
      may contribute to the very high mortality rate from cardiovascular causes in the
      end-stage renal disease population. Vascular calcification in chronic renal
      failure can arise from the calcification of the intimal layer of arteries as a
      result of atherosclerosis or from medial wall calcification due largely to
      alterations in mineral metabolism. Although several reports indicate that
      coronary artery calcification, as measured by electron-beam computed tomography,
      is quite common in patients with end-stage renal disease who are treated with
      dialysis, the clinical significance of these findings remain uncertain. In the
      general population, electron-beam computed tomography evidence of coronary
      calcification serves as a useful index of atherosclerotic burden and has value as
      a predictor of adverse coronary events. The relationship between coronary artery
      calcification and atherosclerotic cardiovascular disease has not been adequately
      studied, however, in patients with end-stage renal disease, and calcification
      scores in this population may reflect both intimal and medial wall calcification.
      Assessments using coronary angiography are needed to determine the diagnostic
      value of electron-beam computed tomography as a predictor of atherosclerotic
      cardiovascular disease in patients with chronic renal failure. Nevertheless,
      electron-beam computed tomography makes it possible to detect the presence and
      monitor the progression of coronary calcification in those undergoing long-term
      dialysis. The technique may provide important information about the impact of new
      therapeutic strategies aimed at reducing the risks of vascular calcification in
      those with chronic renal failure.

PMID- 11342800
TI  - Uric acid and cardiovascular disease: a renal-cardiac relationship?
AB  - Elevated serum uric acid is a frequent finding in patients with kidney disease
      and cardiovascular disease. Intrarenal ischaemia, induced by hypertension,
      increased sympathetic nervous system activity, and hyperinsulinaemia have all
      been implicated in reduced renal clearance of urate. This frequently results in
      elevated serum uric acid levels. The association of hyperuricaemia with
      cardiovascular disease remains controversial. Current evidence suggests that
      serum uric acid may provide additional prognostic information in patients with
      essential hypertension. However, there has been no test of the hypothesis that a
      reduction in serum uric acid would prevent cardiovascular disease. Furthermore, a
      critical review of the current literature does not support a causal role of serum
      uric acid in the development of cardiovascular disease. Serum uric acid probably
      reflects and integrates different risk factors and their possible interactions.

PMID- 11342801
TI  - Associations of homocysteine, C-reactive protein and cardiovascular disease in
      patients with renal disease.
AB  - In the past year, evidence from epidemiological studies in patients with renal
      disease has confirmed associations between both elevated plasma total
      homocysteine concentrations and the inflammatory marker C-reactive protein with
      an increased risk of arteriosclerotic vascular disease. However, it remains to be
      determined whether lowering total homocysteine or reducing inflammation will
      prevent 'hard' clinical outcome events such as stroke, myocardial infarction, and
      vascular death. Randomized trials of homocysteine lowering are currently ongoing
      and should further clarify the nature of the observed association between
      elevated total homocysteine and cardiovascular risk in patients with or without
      renal disease, and whether it is causal and modifiable. There are currently no
      known therapeutic interventions that specifically lower C-reactive protein levels
      in individuals or the prevalence of elevated C-reactive protein in the population
      but randomized trials of anti-inflammatory therapy (e.g. using selective cyclo
      oxygenase-2 inhibitors) aimed at preventing cardiovascular disease are currently
      being planned.

PMID- 11342802
TI  - Alcohol: role in the development of hypertension and end-stage renal disease.
AB  - Alcohol is a common risk factor in the general population for a variety of health
      outcomes. In the present review, we discuss the recent literature on alcohol,
      hypertension, and renal disease. The regular consumption of more than two drinks
      per day is associated with both hypertension and renal disease. The mechanisms by
      which consumption of alcohol leads to hypertension and perhaps renal disease are
      unknown.

PMID- 11342803
TI  - Control of blood pressure in the ambulatory setting.
AB  - Control of blood pressure still relies on conventional office or clinical blood
      pressure measurement using mercury sphygmomanometry. However, it has long been
      known that office measurement, even when repeated, does not fully reflect usual
      blood pressure. The additional use of ambulatory devices for prolonged periods of
      blood pressure measurement is now clinically feasible. Previous research has
      indicated that ambulatory blood pressure measurement is better than office
      measurement at predicting individual cardiovascular risk. Guidelines for clinical
      use of ambulatory blood pressure measurement and for quality control of devices
      are available. Ambulatory measurement has revealed characteristics of circadian
      rhythm and variability that are promising with regard both to improving our
      understanding of the aetiology of high blood pressure and to individual risk
      assessment. Some of the latest developments in research on ambulatory blood
      pressure measurement are discussed.

PMID- 11342804
TI  - Evaluation and treatment of renal artery stenosis: impact on blood pressure and
      renal function.
AB  - The conventional non-invasive tests to diagnose renal artery stenosis in a
      general hypertensive population are not accurate enough for screening purposes.
      Magnetic resonance angiography might become the new gold standard, with the
      advantages of the absence of contrast toxicity, good accuracy, and information on
      flow characteristics. With regard to the treatment of hypertension in patients
      with renal artery stenosis, intervention is advised only when blood pressure
      cannot be controlled by at least three antihypertensive drugs. Patency after
      stenting is superior to angioplasty, although its clinical benefit has not been
      proved. As for renal function, evidence - although from uncontrolled studies -
      for the preservation of renal function by intervention is accumulating,
      especially in those patients with bilateral stenosis or stenosis in a single
      functioning kidney.

PMID- 11342805
TI  - Bouncing the question from the whole animal to the test tube and back.

PMID- 11342806
TI  - Factor V Leiden mutation: potential thrombogenic role in renal vein, dialysis
      graft and transplant vascular thrombosis.
AB  - Factor V is an important blood coagulation factor, the procoagulatory activity of
      which is inhibited by activated protein C. The factor V Leiden mutation is due to
      a single base-pair change (G1691A), which alters the initial cleavage site for
      activated protein C. The impaired degradation of factor V by activated protein C
      yields a hypercoagulable state that confers a lifelong increased risk of
      thrombosis in heterozygous and homozygous individuals. The factor V Leiden
      mutation represents the most common cause of inherited thrombophilia, and
      enhances the risk for venous thrombosis by approximately sevenfold. In normal
      Western populations, heterozygosity for the factor V Leiden mutation is present
      in 2-5%, whereas in patients with venous thrombosis and a family history of
      thrombotic disease this figure may reach 50-60%. The presence of the mutation
      markedly increases the risk for renal vein thrombosis, particularly in neonates.
      Heterozygosity for factor V Leiden mutation does not appear to be a major risk
      factor for dialysis access clotting. The presence of factor V Leiden mutation is
      most devastating in kidney transplant recipients. In these patients the mutation
      predisposes to renal transplant vein thrombosis and early graft loss. The risk
      for acute vascular rejection is also enhanced in transplant recipients who are
      heterozygous for the mutation. Routine screening for factor V Leiden mutation by
      polymerase chain reaction, and appropriate perioperative and postoperative
      anticoagulation after renal transplantation might be a valuable strategy to
      prevent thromboembolic complications in transplant recipients.

PMID- 11342807
TI  - Role of ClC-5 in the pathogenesis of hypercalciuria: recent insights from
      transgenic mouse models.
AB  - Dent's disease is an inherited disorder characterized by hypercalciuria, low
      molecular weight proteinuria, and Fanconi syndrome, which is caused by
      inactivating mutations in ClC-5, a chloride channel expressed in endosomes of the
      proximal renal tubule. The role of ClC-5 in the pathogenesis of the
      hypercalciuria and other myriad manifestations of this disease, however, is
      largely unknown. New insights from three new transgenic mouse models of Dent's
      disease, reported in the past year, are discussed.

PMID- 11342808
TI  - Is there an optimal parathyroid hormone level in end-stage renal failure: the
      lower the better?
AB  - Skeletal resistance to parathyroid hormone is well defined in patients with
      chronic renal failure. In recent years, with the increased frequency of
      development of adynamic bone disease, it has been recognized that secondary
      hyperparathyroidism must exist as a 'trade off' mechanism to maintain skeletal
      bone remodeling in this patient population. An optimal level of intact
      parathyroid hormone to maintain the normal skeletal bone turnover is believed to
      be between 2.0 and 2.5 times the upper limit of normal parathyroid hormone. It
      has very recently been argued that the optimal parathyroid hormone level for
      maintenance of skeletal bone remodeling may be insufficient to prevent the
      extraskeletal complications of coronary artery calcifications, calcific valvular
      heart disease, and cardiac death. To provide optimal health care for these
      patients several new treatments have been developed, including use of new vitamin
      D analogs, calcimimetic agents, and noncalcium-based phosphorus binders. It is
      anticipated that with lower suppression of parathyroid hormone by these vitamin D
      analogs, intermittent suppression of parathyroid hormone with calcimimetic
      agents, and the use of noncalcium phosphorus binders (Renageltrade) by regulating
      serum calcium, the resultant phosphorus concentrations will provide an optimal
      parathyroid hormone activity to maintain skeletal bone remodeling, while
      preventing extraskeletal complications.

PMID- 11342809
TI  - Genes and proteins involved in mesenchymal to epithelial transition.
AB  - It has been known for many years that the epithelia of the urogenital system
      derive from mesenchyme. Essential regulators of this conversion have recently
      been discovered, and cellular changes have been described. However, we do not
      have a coherent view of how these dramatic changes are integrated, nor do we know
      the source or identity of extracellular signals that must regulate
      epithelialization of mesenchymal precursors. The metanephric kidney, Wolffian
      duct, and the Drosophila midgut are the leading model systems to describe how
      epithelia derive from mesenchyme.

PMID- 11342810
TI  - The genetics of lupus.
AB  - The complex multifactorial inheritance pattern of systemic lupus erythematosus in
      various murine models has been dissected via both classic genetic analysis and
      the use of modern technologies in genomic manipulation. Current information
      suggests that lupus may be mediated by a multitude of genetic abnormalities that
      impact on specific checkpoints in a three-step pathogenic pathway. These steps
      are as follows: loss of immunologic tolerance to nuclear antigens; the transition
      to pathogenic autoimmunity; and end-organ targeting. The identities of the genes
      that are responsible for transition between the specific steps of the pathway are
      still unknown and will require further study. However, several recent findings
      have provided insights into specific elements in each stage of lupus. These
      findings suggest that mouse models of lupus may provide valuable insights into
      the genetic basis of human systemic lupus erythematosus.

PMID- 11342811
TI  - Nanobacteria: controversial pathogens in nephrolithiasis and polycystic kidney
      disease.
AB  - Nanobacteria are unconventional agents 100-fold smaller than common bacteria that
      can replicate apatite-forming units. Nanobacteria are powerful mediators of
      biogenic apatite nucleation (crystal form of calcium phosphate) and crystal
      growth under conditions simulating blood and urine. Apatite is found in the
      central nidus of most kidney stones and in mineral plaques (Randall's plaques) in
      renal papilla. The direct injection of nanobacteria into rat kidneys resulted in
      stone formation in the nanobacteria-injected kidney during one month follow-up,
      but not in the control kidney injected with vehicle. After intravenous
      administration in rats and rabbits, nanobacteria are rapidly excreted from the
      blood into the urine, as a major elimination route, and damage renal collecting
      tubuli. Nanobacteria are cytotoxic to fibroblasts in vitro. Human kidney cyst
      fluids contain nanobacteria. Nanobacteria thus appear to be potential
      provocateurs and initiators of kidney stones, tubular damage, and kidney cyst
      formation. It is hypothesized that nanobacteria are the initial nidi on which
      kidney stone is built up, at a rate dependent on the supersaturation status of
      the urine. Those individuals having both nanobacteria and diminished defences
      against stone formation (i.e. genetic factors, diet and drinking habits) could be
      at high risk. Kidney cyst formation is hypothesized to involve nanobacteria
      induced tubular damage and defective tissue regeneration yielding cyst formation,
      the extent of which is dependent on genetic vulnerability.

PMID- 11342813
TI  - AUA Urology Research Announcements.

PMID- 11342882
TI  - Re: Ureteropelvic junction obstruction: long-term followup of adults with and
      without surgical treatment.

PMID- 11342885
TI  - The intrarenal resistive index as a pathophysiological marker of obstructive
      uropathy.
AB  - PURPOSE: The intrarenal resistive index is a physiological parameter that
      indirectly reflects the degree of resistance in the intrarenal vasculature.
      Resistive index measurements have been advocated for the diagnostic evaluation of
      several renal pathologies, including obstructive uropathy. However, despite
      extensive research in this field during the last decade clear guidelines on the
      use of resistive index measurements for discriminating obstructive from
      nonobstructive dilatation of the upper urinary tract remain elusive. Therefore,
      we reviewed the literature to clarify the proper role of resistive index
      measurements in the context of obstructive uropathy. MATERIALS AND METHODS: We
      reviewed the recent literature on the use of resistive index measurements for the
      diagnostic evaluation of obstructive uropathy. RESULTS: Despite a continuously
      growing body of literature the resistive index has yet to be recognized as a
      dependable parameter when it comes to resolving the long-standing dilemma of the
      dilated upper urinary tract. While proponents have observed that this method has
      sensitivity and specificity that supersede those of conventional methods,
      opponents have reported that the resistive index is an unreliable parameter that
      is prone to systemic and local influences. CONCLUSIONS: Resistive index
      measurements are still in a developmental phase. Additional studies are needed
      before this technique may be used reliably for the diagnosis of obstructive
      uropathy.

PMID- 11342886
TI  - Susruta, the pioneer urologist of antiquity.
AB  - PURPOSE: Susruta, a pioneer surgeon of antiquity, practiced around 1000 BC in
      India. We review his many contributions with special reference to the management
      of urological ailments. MATERIALS AND METHODS: Information gleaned from the
      available English translation of 3 volumes of Susruta's treatise in surgery is
      analyzed with commentaries and historical perspectives chronicled by Oriental and
      Occidental historians. RESULTS: Susruta belonged to the period between 600 and
      1000 BC. His conceptions of anatomy, physiopathology and therapeutic strategies
      were of unparalleled brilliance, considering the early age in the history of
      mankind with no supportive knowledge base preceding his era. His discussions of
      many aspects of urological diseases are often reaffirmed in the principles of
      urology today. CONCLUSIONS: Through his rational understanding, elaborate
      teachings and practice of the art of surgery, and many urological ailments in
      particular Susruta has earned the glory of being the pioneer urologist of
      antiquity.

PMID- 11342887
TI  - Prostate cancer detection in men with prior high grade prostatic intraepithelial
      neoplasia or atypical prostate biopsy.
AB  - PURPOSE: We used clinical variables to predict prostate cancer detection on re
      biopsy among patients diagnosed with high grade prostatic intraepithelial
      neoplasia (PIN) or atypia on initial prostate biopsy. MATERIALS AND METHODS: A
      total of 45 men with atypia and 43 with high grade PIN were eligible for our
      study. Clinical variables were tested with univariate and multivariate logistic
      regression to predict who would have cancer on re-biopsy. We also calculated the
      odds of detecting cancer with various repeat sampling strategies and determined
      whether the location of initial atypia or high grade PIN is correlated to that of
      cancer on re-biopsy. RESULTS: Of the patients in the atypia and high grade PIN
      groups 51% had cancer on re-biopsy. Cancer was diagnosed significantly earlier in
      the high grade PIN than in the atypia cohort (average 7.5 versus 22.9 months,
      respectively, p = 0.005). Multivariate logistic modeling showed that digital
      rectal examination and patient age were independent predictors of cancer in
      atypia, whereas no variables were significantly predictive for high grade PIN. Of
      cancers in the atypia and high grade PIN 65% and 74%, respectively, would have
      been detected if re-biopsy was focused only at the initial site of disease.
      CONCLUSIONS: Men with atypia or high grade PIN merit close followup because 50%
      will have cancer on re-biopsy as will those who are older with an abnormal
      digital rectal examination. Although re-biopsy should focus primarily on the
      original site of atypia or high grade PIN, cancer detection significantly
      increases with the sampling of adjacent sites.

PMID- 11342888
TI  - Impact of lower pole renal anatomy on stone clearance after shock wave
      lithotripsy: fact or fiction?
AB  - PURPOSE: We determined whether there is a significant relationship between the
      spatial anatomy of the lower pole on preoperative excretory urography and stone
      fragment clearance after shock wave lithotripsy. MATERIALS AND METHODS: The
      anatomical factors affecting lower pole stone clearance after shock wave
      lithotripsy were evaluated retrospectively in 108 patients. Stone-free status was
      assessed by renal computerized tomography with or without renal ultrasound. The
      stone-free rate at 3 months was correlated with lower pole infundibular length
      and width in mm. as well as with the lower pole infundibulopelvic angle in
      degrees. The statistical significance of each lower pole anatomical factor as
      well as other stone, renal and treatment factors were correlated with the stone
      free rate using the Mann-Whitney and chi-square tests. RESULTS: Three months
      after shock wave lithotripsy 79 patients (73.1%) were free of stones. Mean lower
      infundibular length plus or minus standard deviation was 20.9 +/- 6.56 mm., mean
      infundibular width was 5.65 +/- 2.34 mm. and the mean lower pole
      infundibulopelvic angle was 48.33 +/- 14.84 degrees. In 49 (45.4%) and 59 (54.6%)
      patients infundibular length was greater than 3 cm. and 3 cm. or less,
      respectively. Infundibular width was greater than 5 mm. and 5 mm. or less in 45
      (41.7%) and 63 (58.3%) patients, respectively. No obtuse infundibulopelvic angles
      were noted. None of the 3 lower pole anatomical factors had any significant
      impact on the stone-free rate at 3 months. Renal morphology was the only factor
      significantly affecting the stone-free rate since stone clearance was
      significantly less in pyelonephritic kidneys (p = 0.0009). CONCLUSIONS:
      Differences in the intrarenal anatomy of the lower pole have no significant
      impact on stone clearance after shock wave lithotripsy. Further examination of
      the lower pole renal anatomy with a search for other contributing factors is
      still warranted.

PMID- 11342889
TI  - A prospective randomized controlled trial comparing nonstented versus stented
      ureteroscopic lithotripsy.
AB  - PURPOSE: A prospective randomized controlled trial was performed to determine
      whether stents may be eliminated after uncomplicated ureteroscopic lithotripsy
      for ureteral stones. MATERIALS AND METHODS: A total of 58 patients underwent
      uncomplicated ureteroscopic intracorporeal lithotripsy. After stone fragmentation
      patients were randomized to a nonstented (29) or a stented (29) treatment group.
      Intracorporeal lithotripsy was performed with the holmium laser in 57 cases and
      by electrohydraulic lithotripsy in 1 without balloon dilation or the extraction
      of stone fragments. Patients were followed 1, 6 and 12 weeks postoperatively. In
      stented cases the stent was removed at 1 week. Outcome measures included
      postoperative symptoms assessed with a visual analog scale, postoperative
      analgesic requirements, complications and the stone-free rate. RESULTS: At 1 week
      the symptoms of flank pain, abdominal pain, dysuria and frequency were
      significantly greater in the stented group (p <0.005). There were no differences
      in symptoms in the groups at subsequent followup visits. There was no difference
      in treatment groups in terms of the amount of analgesic required in the recovery
      room or during 1 week after ureteroscopy. Similarly there was no difference in
      the number of patients requiring antiemetics. One patient in the stented group
      required hospitalization for genitourinary sepsis and 1 patient in the nonstented
      group visited the emergency room for postoperative vomiting. The stone-free rate
      was 100% in each group. CONCLUSIONS: These results demonstrate that after
      ureteroscopic intracorporeal lithotripsy with the holmium laser patients with a
      stent have significantly greater irritative and painful symptoms than those
      without a stent in the early postoperative period. There was no difference in
      nonstented and stented ureteroscopy with respect to complications or stone-free
      status. Therefore, we believe that routine stenting after ureteroscopic
      intracorporeal lithotripsy with the holmium laser is not required as long as the
      procedure is uncomplicated and performed without balloon dilation of the ureteral
      orifice.

PMID- 11342890
TI  - The Hadera continent reservoir: a new appendico-umbilical continent stoma
      mechanism for urinary diversion.
AB  - PURPOSE: Creating a reliable continence mechanism for a continent reservoir is a
      great challenge. We describe an easily formed mechanism for allowing complete
      continence in such patients. MATERIALS AND METHODS: The native appendix attached
      to a detubularized right colonic reservoir was used as the catheterizable
      efferent limb. The continence mechanism was created by crossing 2 nondetached
      right rectus muscle strips around the appendix. RESULTS: At a mean followup of 32
      months (range 4 to 52) in 17 patients complete continence was obtained between 2
      to 4-hour self-catheterizations in all positions and even during straining.
      CONCLUSIONS: This continence mechanism is easy to construct and creates a
      reliable continent stoma in all patients who are not candidates for orthotopic
      bladder replacement and who retain the native appendix. In patients who have
      undergone appendectomy an alternate method is to create a small caliber efferent
      limb from a tailored terminal ileum and build the continence mechanism around it.

PMID- 11342891
TI  - Functional results of orthotopic ileal neobladder with serous-lined extramural
      ureteral reimplantation: experience with 450 patients.
AB  - PURPOSE: We report functional results of the orthotopic ileal neobladder using a
      serous-lined extramural tunnel as an antireflux procedure. MATERIAL AND METHODS:
      One-stage radical cystectomy and orthotopic ileal W-shaped neobladder creation
      were performed in 353 male and 97 female patients for invasive bladder cancer.
      The ureters were reimplanted using a serous-lined extramural tunnel for reflux
      prevention. Of the patients 344 were evaluable at a mean followup plus or minus
      standard deviation of 38 +/- 25 months. Evaluation included clinical and
      radiographic studies to determine functional and oncological outcomes. RESULTS:
      Four patients (0.8%) died in the hospital. Early complications in 42 patients
      (9%) were treated conservatively but 3 women underwent vaginal repair of a pouch
      vaginal fistula. During the observation period there were 90 oncological
      failures, of which 3 were isolated urethral recurrence. Late complications
      included pouch stones in 10 cases, outflow obstruction in 11, mucous retention in
      2, adhesive bowel obstruction in 3 and hypercontinence in 9 females. The
      incidence of daytime and nighttime continence was 93.3% and 80%, respectively.
      The upper tracts remain unchanged or improved in 96.2% of the reimplanted renal
      units, while reflux was observed in 3%. CONCLUSIONS: The serous-lined extramural
      tunnel has proved its efficiency and durability as an antireflux technique.

PMID- 11342892
TI  - Reducing mucus production after urinary reconstruction: a prospective randomized
      trial.
AB  - PURPOSE: After transposition into the urinary tract, intestinal segments continue
      to produce mucus. We determine the effectiveness of muco-regulatory drugs,
      including N-acetylcysteine, aspirin and ranitidine, in reducing mucus secretion
      and urine viscosity in patients with transposed segments. MATERIALS AND METHODS:
      Our trial was a prospective randomized, double-blind placebo controlled crossover
      study involving 12 patients who underwent ileal conduit and 31 who underwent
      bladder reconstruction. Each treatment lasted 3 weeks with a 2-week washout.
      Pretreatment and posttreatment 24-hour urine samples were analyzed for mucin and
      viscosity after papain digestion, sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis and periodic acid-Schiff assay. A disease specific questionnaire
      and SF-36 quality of life survey were completed. RESULTS: According to the
      questionnaire, mucus production did not decrease with time in 67% of patients.
      Mucin comprised 3% of the total nondialyzable material in urine (65 mg./24-hour
      for ileal conduit and 60 mg./24-hour for bladder reconstruction). Analysis of
      questionnaires and laboratory results failed to demonstrate any benefit of taking
      muco-regulatory agents compared with placebo. CONCLUSIONS: The use of N
      acetylcysteine, aspirin and ranitidine did not result in a reduction in mucin
      production, urine viscosity or improvement in quality of life.

PMID- 11342893
TI  - The effect of cholinergic enhancement during filling cystometry: can edrophonium
      chloride be used as a provocative test for overactive bladder?
AB  - PURPOSE: Overactive bladder, a highly prevalent disorder, is suspected of having
      a low detection rate due to the lack of sensitive diagnostic tools. Recent
      studies imply the involvement of the cholinergic system in the pathophysiological
      mechanism underlying overactive bladder. We determined whether in vivo
      enhancement of cholinergic activity with edrophonium chloride, a potent
      cholinesterase inhibitor, would serve as a provocative maneuver to increase the
      sensitivity of filling cystometry. MATERIALS AND METHODS: A total of 27 patients
      underwent a multichannel video urodynamic evaluation, followed by filling
      cystometry with the intravenous administration of 10 mg. edrophonium chloride.
      The response to edrophonium was defined as a significant change in sensation and
      decreased bladder capacity, the induction or amplification of involuntary
      detrusor contractions, or significantly decreased detrusor compliance. Findings
      were compared in responders and nonresponders. RESULTS: We identified 11
      responders and 16 nonresponders. A response was noted in 78% of the patients with
      the symptomatology of overactive bladder but in none with no specific complaints
      suggesting bladder overactivity. In 7 of the 12 responders (64%) baseline
      cystometry was interpreted as normal. In 6 of the 11 responders (54%) uninhibited
      urinary leakage was observed in response to edrophonium. There were no serious
      adverse reactions to the drug. CONCLUSIONS: This preliminary study implies that
      edrophonium may serve as a novel, practical and safe drug for provocative
      cystometry. By significantly increasing cystometry sensitivity the drug would
      facilitate the identification of the subset of patients with overactive bladder
      who are currently classified with sensory urgency.

PMID- 11342894
TI  - A pharmacokinetic and pharmacodynamic comparison of desmopressin administered as
      whole, chewed and crushed tablets, and as an oral solution.
AB  - PURPOSE: We performed a crossover study to determine the relative pharmacokinetic
      bioavailability and antidiuretic activity of desmopressin in 16 orally hydrated,
      healthy human subjects. MATERIALS AND METHODS: The investigation included 5 study
      periods with 1 period used to establish baseline diuresis in the absence of
      desmopressin and the remaining 4 randomized to a single 0.6 mg. oral dose of
      desmopressin administered as whole, crushed or chewed tablets, or as an oral
      solution. Serial plasma samples were collected for 12 hours for desmopressin
      pharmacokinetic analysis. Pharmacodynamics were assessed by measuring changes in
      urine volume and osmolality from baseline. Standard bioequivalence metrics were
      used to compare the pharmacokinetics and pharmacodynamics of crushed and chewed
      tablets, and oral solution to that of swallowing whole tablets. RESULTS: The 90%
      confidence interval analysis of log transformed plasma desmopressin area under
      the plasma concentration-time curve from time 0 to infinity and maximum plasma
      drug concentration showed that crushed and chewed tablet treatments were
      bioequivalent to swallowing whole tablets. The 90% confidence interval analysis
      for the decrease in urine volume and increase in urine osmolality demonstrated
      that crushed and chewed tablets, and oral solution treatments were equivalent to
      whole tablet treatment in the area under curve from time 0 to the last sampling
      time point and maximum drug effect. CONCLUSIONS: The results of this study imply
      that desmopressin administered orally as crushed or chewed tablets, or as an oral
      solution has the same net effect on decreasing urine volume and increasing urine
      osmolality as swallowing tablets whole.

PMID- 11342895
TI  - Tolterodine: superior tolerability than and comparable efficacy to oxybutynin in
      individuals 50 years old or older with overactive bladder: a randomized
      controlled trial.
AB  - PURPOSE: We compared the tolerability and clinical efficacy of tolterodine with
      those of oxybutynin in patients with an overactive bladder using an upward
      oxybutynin dose titration strategy analogous to that used in routine clinical
      practice in the United Kingdom and Republic of Ireland. MATERIALS AND METHODS: In
      a randomized double-blind trial 378 male and female patients 50 years old or
      older with symptoms of overactive bladder (a urinary frequency of 8 or more voids
      per 24 hours with urgency and/or urge incontinence, that is 1 or more urge
      incontinence episodes per 24 hours) received 10 weeks of treatment with 2 mg.
      tolterodine twice daily/or an initial dose of 2.5 mg. oxybutynin twice daily,
      increasing to 5 mg. twice daily after 2 weeks of treatment. The main outcome
      measures were changes in voiding diary variables combined with detailed
      tolerability-safety assessments. RESULTS: Patients treated with tolterodine had
      significantly fewer adverse events (69% versus 81%, p = 0.01), notably dry mouth
      (37% versus 61%, p <0.0001), as well as a lower incidence of dose reduction (6%
      versus 25%, p <0.0001) than those in the oxybutynin group. Each agent had
      comparable efficacy for improving urinary symptoms. Tolterodine and oxybutynin
      caused a significant decrease (p = 0.0001) in the mean number of voids per 24
      hours (-1.7 or -15% and -1.7 or -15%, respectively), urge incontinence episodes
      per 24 hours (-1.3 or -54% and -1.8 or -62%, respectively) and mean voided volume
      per void (33 ml. or 22% and 34 ml. or 23%) after 10 weeks of treatment.
      CONCLUSIONS: Tolterodine is as effective as oxybutynin for improving the symptoms
      of overactive bladder but it has superior tolerability. The combination of these
      qualities makes tolterodine the preferred pharmacological therapy for the long
      term treatment of this condition.

PMID- 11342896
TI  - Inducible nitric oxide synthase in the bladder of spinal cord injured patients
      with a chronic indwelling urinary catheter.
AB  - PURPOSE: Spinal cord injured patients are at increased risk for bladder
      carcinoma. Nitric oxide production in areas of chronic inflammation may provide a
      stimulus for carcinogenesis by serving as a source of nitrosating agents that
      generate potentially carcinogenic nitrosamines from secondary amines normally
      present in urine. MATERIALS AND METHODS: To determine whether inducible nitric
      oxide synthase is expressed as a catalyst for sustained nitric oxide production
      by cellular elements in chronically inflamed bladder mucosa immunohistochemical
      studies were performed on mucosal biopsies obtained from 37 adults with spinal
      cord injury. All participants had required a chronic indwelling urethral or
      suprapubic catheter for greater than 8 years. RESULTS: Histopathological studies
      revealed active inflammatory infiltrates in all 37 biopsy specimens, squamous
      metaplasia in 20, epithelial dysplasia in 3 and carcinoma in 1. Inducible nitric
      oxide synthase was detected in inflammatory cells localized to the lamina
      propria. Inducible nitric oxide synthase positive cells were identified as
      macrophages using monoclonal antibodies to macrophage antigen. There was no
      inducible nitric oxide synthase expression in the urothelial cell layers.
      Immunostaining for inducible nitric oxide synthase was not detected in bladder
      mucosal biopsy specimens obtained from cadaveric organ donors. CONCLUSIONS:
      Inducible nitric oxide synthase is expressed in inflammatory macrophages in areas
      of chronic inflammation in the bladder mucosa of spinal cord injured patients
      with a chronic indwelling bladder catheter. The expression of inducible nitric
      oxide synthase may potentially lead to the sustained production of nitric oxide
      and its oxidative products, the nitrosation of urinary amines and the formation
      of potentially carcinogenic nitrosamines in the bladder.

PMID- 11342897
TI  - Comparative predictive values of urinary cytology, urinary bladder cancer
      antigen, CYFRA 21-1 and NMP22 for evaluating symptomatic patients at risk for
      bladder cancer.
AB  - PURPOSE: We study the potential diagnostic use of urinary bladder cancer antigen,
      CYFRA 21-1 and NMP22*; for evaluating symptomatic patients who present with
      microscopic hematuria and are at risk for bladder cancer. MATERIALS AND METHODS:
      Urinary tumor markers were determined in 187 samples from 112 patients
      symptomatic of bladder cancer (group 1), and 75 with benign and other urological
      conditions (group 2). Immunoassays were used to measure the 3 selected
      biomarkers. Sensitivity and specificity were established by previously defined
      cut points. Biomarker results were reported as corrected and uncorrected for
      urinary creatinine. Urinalysis was performed in all samples. RESULTS: Positive
      and negative predictive values were 85.5%, 80.5% and 81.1%, and 80.8%, 79.2% and
      76.5% for urinary bladder cancer antigen, CYFRA 21-1 and NMP22, with the cutoffs
      9.7 microg./l., 5.4 microg./l and 10.0 units per ml., respectively. These
      predictives values were 85.2% and 72.5%, respectively, for urinary cytology. The
      combination of biomarkers decreased the positive predictive values to 72.3% to
      78.6% and increased negative predictive values to 84.2% to 86.1%. Urinary tract
      infection, inflammation and malignancy associated with other genitourinary organs
      were the primary cause for false-positive test results in the 3 assays evaluated.
      CONCLUSIONS: With a single biomarker, around 80% of the positive results would
      have correctly identified symptomatic patients for cystoscopy. Of the negative
      results 75% would have correctly reduced the number of cystoscopies. Sensitivity
      and negative predictive values could be improved with the combination of
      biomarkers but with a loss of specificity and positive predictive values. Urinary
      tract inflammation and other genitourinary malignancies might contribute to the
      reduction in specificity of these tests.

PMID- 11342898
TI  - Expression of cyclooxygenase-2 in patients with bladder carcinoma.
AB  - PURPOSE: Cyclooxygenase-2 is considered to have an important role in the
      development of metastasis in cancer due to angiogenesis function. The expression
      of cyclooxygenase-2 was found to be up-regulated in colorectal carcinoma and
      other cancers. We investigated cyclooxygenase-1 and 2 expressions in patients
      with bladder cancer, chronic cystitis and normal bladder. MATERIALS AND METHODS:
      A total of 118 specimens were obtained from patients treated at Osaka City
      University Hospital for bladder cancer, including 10 with chronic cystitis and 8
      with normal bladder tissue. Immunohistochemistry, with affinity purified
      antibodies against human cyclooxygenase-1 and 2 that did not have cross
      reactivity with each other, and reverse transcriptase polymerase chain reaction
      to study the messenger RNA expression were performed. RESULTS: Although no marked
      expression of cyclooxygenase-2 was observed in the normal bladder, it was
      slightly seen in infiltrative inflammatory cells of chronic cystitis, and a
      higher expression was found in cancer cells. The extent and intensity of
      immunoreactive cyclooxygenase-2 polypeptides in cancer cells was statistically
      much greater than those in cells from normal bladder tissue. Moreover,
      correlation between cyclooxygenase-2 expression and tissue type or progression of
      bladder cancer was observed. Cyclooxygenase-2 expression was higher in grade 3
      bladder cancer than in grade 1, and was higher in advanced than in early stage
      cancer. CONCLUSIONS: These results demonstrate that generated cyclooxygenase-2 in
      the cells of patients with bladder cancer might be significant in the
      proliferation of bladder malignant cells and development of invasions.

PMID- 11342899
TI  - E-cadherin immunostaining of bladder transitional cell carcinoma, carcinoma in
      situ and lymph node metastases with long-term followup.
AB  - PURPOSE: We analyze the expression of E-cadherin in bladder transitional cell
      carcinoma, areas of carcinoma in situ and lymph node metastases, and determine
      the value of E-cadherin immunoreactivity for predicting disease progression and
      survival of patients with bladder transitional cell carcinoma. MATERIALS AND
      METHODS: The study group consisted of 77 patients who underwent radical
      cystectomy. Formalin fixed paraffin sections were processed with a hot, citric
      acid antigen retrieval method, followed by immunostaining with anti-E-cadherin
      monoclonal antibody and a standard avidin biotin complex technique. E-cadherin
      expression was also evaluated in carcinoma in situ sections (18) and in regional
      lymph node metastases (17). RESULTS: Loss of normal membrane E-cadherin
      immunoreactivity was found in 59 (77%) patients. Abnormal expression of E
      cadherin was associated with muscle invasive disease (p = 0.010) and lymph node
      metastasis (p = 0.044). Of the 18 carcinoma in situ specimens 15 (83%) and of the
      17 metastatic lymph nodes 13 (76%) had abnormal E-cadherin expression.
      Concordance rates of E-cadherin status in carcinoma in situ areas and metastatic
      lymph nodes with the primary tumors were 85% and 88%, respectively. At a median
      followup of 128 months, abnormal E-cadherin expression was significantly
      associated with disease progression (p = 0.0219) and bladder cancer specific
      survival (p = 0.037). E-cadherin expression and pathological stage but not grade
      were independent predictors of disease progression (p = 0.042, 0.047 and 0.158,
      respectively). CONCLUSIONS: In bladder cancer altered E-cadherin expression is
      associated with the degree of invasiveness, lymph node metastasis and increased
      risk of death from bladder cancer. Furthermore, E-cadherin status is an
      independent predictor of disease progression in patients treated with cystectomy
      for transitional cell carcinoma of the bladder.

PMID- 11342900
TI  - Macroscopic, microscopic and molecular observations of bladder cancer.

PMID- 11342901
TI  - Bilharzial related, organ confined, muscle invasive bladder cancer: prognostic
      value of apoptosis markers, proliferation markers, p53, E-cadherin, epidermal
      growth factor receptor and c-erbB-2.
AB  - PURPOSE: We investigated the association of the apoptosis related proteins Bcl-2,
      Bcl-x, Bax and Bak, p53, the adhesion molecule E-cadherin, the receptor proteins
      epidermal growth factor receptor and c-erbB-2, and the proliferation markers
      proliferating cell nuclear antigen and Ki-67 with the clinical outcome of
      bilharzial related transitional cell carcinoma and squamous cell carcinoma.
      MATERIALS AND METHODS: Cystectomy specimens from 109 patients with organ
      confined, muscle invasive stage, pT2pN0M0, bilharziall positive bladder cancer
      were examined, including 60 with squamous cell carcinoma and 49 with transitional
      cell carcinoma. Immunohistochemical results were correlated with tumor
      progression. RESULTS: In squamous cell carcinoma but not in transitional cell
      carcinoma the loss of epidermal growth factor receptor, Bax and Bak was
      significantly associated with higher histological grade (p = 0.02, 0.006 and
      0.01, respectively). On univariate analysis patients with transitional cell
      carcinoma had a poorer prognosis than those with squamous cell carcinoma. p53
      Over expression and the loss of Bak positivity were associated with shortened
      progression-free survival in transitional cell carcinoma (p = 0.006 and 0.04,
      respectively), and squamous cell carcinoma (p = 0.00001 and 0.04, respectively).
      In squamous cell carcinoma high tumor grade (p = 0.02) and in transitional cell
      carcinoma high labeling indexes for MIB-1, Bcl-x expression and c-erbB-2
      positivity (p = 0.03, 0.02 and 0.04, respectively) were associated with a poorer
      prognosis. On multivariate analysis p53 emerged as a significant prognostic
      factor for each condition. Additional independent prognostic factors were
      proliferating cell nuclear antigen for squamous cell carcinoma, and MIB-1, Bcl-x
      and Bax for transitional cell carcinoma. CONCLUSIONS: Bilharzial related
      transitional cell carcinoma and squamous cell carcinoma of the bladder differ in
      interims of protein expression and prognosis. Independent prognostic factors were
      p53, MIB-1, Bcl-x, and Bax in the former disease, and p53 and proliferating cell
      nuclear antigen in the latter disease.

PMID- 11342902
TI  - Control group and maintenance treatment with bacillus Calmette-Guerin for
      carcinoma in situ and/or high grade bladder tumors.
AB  - PURPOSE: Intravesical instillations of bacillus Calmette-Guerin have demonstrated
      satisfactory results in the treatment of vesical carcinoma in situ and high grade
      superficial bladder tumors. We designed a protocol to evaluate the decrease in
      tumor recurrence with maintenance therapy. MATERIALS AND METHODS: Between June
      1989 and May 1995 an initial course of 6 intravesical instillations of Connaught
      strain bacillus Calmette-Guerin was administered in patients with carcinoma in
      situ and/or high grade superficial bladder tumors. Six months later 131 disease
      free patients were randomly assigned to a control group or a maintenance therapy
      group that received 6 instillations every 6 months (6 x 6) for a 2-year period.
      RESULTS: Of the 126 evaluable patients at a mean followup of 79 months there were
      no significant differences in recurrence nor progression. A total of 16 patients
      (26.2%) in the control and 10 (15.1%) in the maintenance group had superficial
      relapse at a mean of 24 and 20 months, respectively (p = 0.07). Eight patients
      underwent radical cystectomy due to bladder contraction in 1, high grade
      superficial recurrence in 4 and disease progression in 3. Of the 65 patients on
      maintenance therapy 22 (33.85%) completed the planned 2-year treatment.
      CONCLUSIONS: Six-month maintenance therapy in patients treated initially for
      carcinoma in situ and/or high grade superficial bladder tumors who are disease
      free at 6 months did not significantly decrease recurrence or progression.

PMID- 11342903
TI  - The nature of urethral injury in cases of pelvic fracture urethral trauma.
AB  - PURPOSE: We examine the urethral injury associated with pelvic fracture that is
      said to be due to a shearing force through the membranous urethra which
      inevitably destroys the urethral sphincter mechanism. MATERIALS AND METHODS: A
      total of 20 asymptomatic cases were prospectively studied, including
      symptomatically, radiologically, endoscopically and urodynamically, 1 to 4 years
      after an apparently successful anastomotic repair of a pelvic fracture urethral
      distraction defect. RESULTS: There was evidence of urethral sphincter function,
      including urodynamically in 11 (55%), endoscopically in 13 (65%) and functionally
      in 17 (85%) patients. CONCLUSIONS: These findings, coupled with surgical
      observation, suggest that the urethral injury associated with pelvic fracture is
      avulsion of the membranous urethra from the bulbar urethra rather than a shearing
      through the membranous urethra, and that some degree of urethral sphincter
      function is preserved in a significant percentage of patients.

PMID- 11342904
TI  - The augmented anastomotic urethroplasty: indications and outcome in 29 patients.
AB  - PURPOSE: A short bulbar stricture of 1 cm. or less is best managed by stricture
      excision and primary anastomosis. However, a dilemma exists when the total length
      of the stricture is too great for excision and anastomosis. Options include
      stricture incision and flap-graft onlay or stricture excision with roof or floor
      strip anastomosis augmented by an onlay. We report our results with the latter
      type of augmented anastomotic urethroplasty. MATERIALS AND METHODS: We
      retrospectively reviewed the charts of 29 patients who underwent augmented
      anastomotic urethroplasty between 1990 and 1999. Retrograde urethrography was
      performed 3 weeks and 3 months postoperatively, and later if the patient was
      symptomatic. When possible, followup clinic notes and x-rays from referring
      physicians were obtained and patients were contacted directly to assess the long
      term outcome. RESULTS: The stricture was in the bulbar urethra in all cases. Six
      patients had a completely obliterative stricture. Mean stricture length was 1.5
      cm. on retrograde urethrography and the mean excised length was 1.2 cm. In 9 of
      the 29 patients a roof strip anastomosis was augmented by a ventral onlay and in
      20 a floor strip anastomosis was formed with a dorsal onlay. Onlays included a
      pedicled skin flap in 7 cases and a graft in 22. Mean onlay length was 4.5 cm. At
      a mean followup of 28 months (range 3 to 126) 27 of the 29 patients (93%) were
      stricture-free and all those surveyed were satisfied with the procedure.
      Complications include new erectile dysfunction in 1 patient, post-void dribbling
      in 13, pseudodiverticulum formation in 2 and subjective penile shortening in 5.
      CONCLUSIONS: Augmented anastomotic urethroplasty is a useful technique for
      strictures that are too long to be managed by excision and primary anastomosis.
      Greater than 90% of the patients are stricture-free and the results seem durable,
      although longer followup is needed. Complications are few and minor.

PMID- 11342905
TI  - Urethral sensitivity and the impact on urinary continence in patients with an
      ileal bladder substitute after cystectomy.
AB  - PURPOSE: After cystectomy and ileal bladder substitution, sensitivity in the
      membranous urethra correlates with postoperative urinary continence. We determine
      whether sensitivity is decreased only in the most proximal part of the urethra or
      also more distally in the bulbar urethra, which would give some indication as to
      which nerves may be injured during radical cystoprostatectomy. MATERIALS AND
      METHODS: The sensory threshold for electrical stimulation was measured with
      double ring electrodes in the membranous urethra, and 2.5 cm. distally to it in
      41 men after cystectomy and ileal bladder substitution, and in a control group of
      29 men. RESULTS: The mean sensory threshold plus or minus standard deviation of
      the membranous urethra was 9 +/- 2 mA. in the control group compared to 26 +/- 11
      mA. in the postoperative group (p <0.001). Mean sensory threshold 2.5 cm. distal
      to the membranous urethra was 8 +/- 3 versus 9 +/- 3 mA. in the control and
      postoperative groups, respectively (not significant). Patients with daytime
      continence had a mean threshold of 22 +/- 8 mA. in the membranous urethra
      compared to 38 +/- 11 mA. in those who were incontinent (p <0.004) and a
      threshold of 8 +/- 3 mA. 2.5 cm. distal to the membranous urethra compared to 8
      +/- 2 mA. in those who were incontinent (not significant). CONCLUSIONS: After
      cystectomy and ileal bladder substitution, urethral sensitivity 2.5 cm. distal to
      the membranous urethra is unaffected by surgery and does not correlate with
      postoperative continence. In contrast, a decreased sensitivity in the membranous
      urethra correlates with an increased risk of postoperative incontinence.
      Preservation of sensitivity in the membranous urethra seems to be an important
      factor for achieving continence after cystectomy and ileal bladder substitution,
      and does not seem to be dependent on the extrapelvic portion of the pudendal
      nerve.

PMID- 11342906
TI  - Prospective validation of the association of local tumor stage and grade as a
      predictive factor for occult lymph node micrometastasis in patients with penile
      carcinoma and clinically negative inguinal lymph nodes.
AB  - PURPOSE: We prospectively validated the association of local tumor stage and
      grade as a predictive factor for occult lymph node micrometastasis in patients
      with penile carcinoma and clinically negative lymph nodes. MATERIALS AND METHODS:
      In a retrospective study of 66 patients we demonstrated the predictive value of
      the association of local tumor stage and grade for occult micrometastasis,
      identifying 3 risk groups. A therapy strategy was designed according to these
      risk groups. A total of 37 consecutive patients were included in a prospective
      study in which the same criteria for risk group allocation and the same
      therapeutic recommendations were used as in the retrospective study. RESULTS: In
      the prospective study we noted positive lymph nodes in 11% of stage T1, 63% of
      stages T2-3, 15% of grade 1, 67% of grade 2 and 75% of grade 3 cases. The
      incidence of positive nodes was 0% in the low, 83.3% in the high and 33.3% in the
      intermediate risk group. These rates were similar to those in the retrospective
      study with no significant difference. CONCLUSIONS: The predictive value of the
      association of local tumor stage and grade for occult lymph node micrometastasis
      was validated in a prospective study. This factor allows the differentiation of 3
      risk groups of patients with high reliability in the low and high risk groups.
      However, other prognostic factors are needed in the intermediate risk group to
      improve the prediction of lymph node involvement.

PMID- 11342907
TI  - Varicocelectomy improves intrauterine insemination success rates in men with
      varicocele.
AB  - PURPOSE: We determined whether varicocele treatment before intrauterine
      insemination significantly affects intrauterine insemination success rates.
      MATERIALS AND METHODS: A total of 58 infertile couples, of whom the women had
      normal evaluations and men had abnormal semen analyses and a history of
      varicocele, were included in this study. They were identified after reviewing the
      charts of all women undergoing intrauterine insemination for male factor
      infertility at our center. Of the men 24 participated in 63 intrauterine
      insemination cycles without varicocele treatment, while in the remaining 34
      varicocele was treated before a total of 101 intrauterine insemination cycles.
      Variables associated with pregnancy or live birth were analyzed using repeat
      measures logistic regression with generalized estimating equation techniques. An
      initial stepwise generalized estimating equation was performed without including
      varicocele treatment status. Subsequently varicocele treatment status and the
      significant associated factors were included in analysis. The semen
      characteristics of untreated and treated varicocele groups were compared with
      repeat measures analysis of variance. RESULTS: On pre-wash semen analysis
      patients with untreated varicocele had significantly higher mean motility plus or
      minus standard error than patients whose varicoceles were treated (48.6% +/- 2.3%
      versus 38.1% +/- 1.8%, p = 0.02). However, no statistically significant
      difference was noted in the mean post-wash total motile sperm count in the
      treated and untreated groups (7.2 +/- 1.0 versus 14.8 +/- 2.6, p = 0.1). Despite
      these findings the pregnancy and live birth rates per cycle were significantly
      higher in patients in whom varicocele was treated than in those without
      varicocele treatment (11.8% versus 6.3%, p = 0.04 and 11.8% versus 1.6%, p =
      0.007, respectively). CONCLUSIONS: Varicocele treatment may not improve semen
      characteristics in all men but it appears to improve pregnancy and live birth
      rates among couples undergoing intrauterine insemination for male factor
      infertility. A functional factor not measured on routine semen analysis may
      affect pregnancy rates in this setting. Men should be screened for varicocele
      before intrauterine insemination is initiated for male factor infertility.

PMID- 11342908
TI  - Germ cell tumor associated primitive neuroectodermal tumors.
AB  - PURPOSE: This retrospective review was done to assess the prognosis and response
      in patients presenting with primitive neuroectodermal tumor admixed with germ
      cell tumor. MATERIALS AND METHODS: Of the 40 patients treated at our institution
      from 1984 to 1999, 15 had initial stage I and 25 had initial metastatic disease.
      Median followup after the diagnosis was 25 months (range 4 to 142). RESULTS: Of
      the 40 patients 15 presented with clinical stage I disease, including 9 treated
      with retroperitoneal lymph node dissection and 6 who elected surveillance. Seven
      of the 9 patients had normal lymph nodes and all continuously had no evidence of
      disease. Two of the 9 patients had lymph nodes involved with teratoma with or
      without primitive neuroectodermal tumor. Retroperitoneal relapse in 5 of the 6
      patients on surveillance was treated with cisplatin based chemotherapy followed
      by post-chemotherapy retroperitoneal lymph node dissection. Residual primitive
      neuroectodermal tumor was noted in 4 of the 5 patients and only 3 of 6 are
      currently without disease at a median followup of 17 months (range 15 to 69). A
      total of 25 patients presented with metastatic disease, of whom 23 underwent
      cisplatin based chemotherapy. Only 3 patients achieved complete remission with
      chemotherapy alone and 2 of the 3 subsequently relapsed. Of the remaining 20
      patients 16 underwent post-chemotherapy retroperitoneal lymph node dissection,
      including 11 with primitive neuroectodermal tumor in the resected specimen. Two
      of these 11 patients have continuously had no evidence of disease, while an
      additional 3 currently have no evidence of disease after further therapy.
      Teratoma was present in the resected specimen in 5 of 16 patients, of whom 2 have
      continuously had no evidence of disease, while an additional 2 currently have no
      evidence of disease after further surgical resection. Therefore, 11 of 25
      patients who presented with metastatic disease currently have no evidence of
      disease at a median followup of 19 months (range 2 to 111). CONCLUSIONS:
      Primitive neuroectodermal tumor in the orchiectomy specimen has adverse
      prognostic significance. This condition in the retroperitoneum is potentially
      curable by retroperitoneal lymph node dissection but rarely eradicated by
      chemotherapy. Therefore, we recommend retroperitoneal lymph node dissection for
      all clinical stage I cases with primitive neuroectodermal tumor in the
      orchiectomy specimen. Patients who present with metastatic primitive
      neuroectodermal tumor should be treated aggressively with surgical resection as
      an integral part of the therapeutic strategy.

PMID- 11342909
TI  - Aortic replacement during post-chemotherapy retroperitoneal lymph node
      dissection.
AB  - PURPOSE: We reviewed the records of 15 patients with metastatic germ cell cancer
      who underwent aortic resection and replacement during post-chemotherapy
      retroperitoneal lymph node dissection to determine the morbidity and the
      therapeutic benefit. MATERIALS AND METHODS: Between 1970 and 1998, 1,250 patients
      underwent post-chemotherapy retroperitoneal lymph node dissection. Our
      retrospective review revealed that 15 patients underwent aortic replacement at
      that operation. RESULTS: In addition to aortic replacement 11 patients underwent
      15 additional procedures, including nephrectomy in 7, vena caval resection in 3,
      pulmonary resection in 1, small bowel resection in 2, 1 hepatic resection in 1
      and L4 vertebrectomy in 1. No patient had necrosis as the only pathological
      condition. Three patients (20%) had teratoma and 12 (80%) had viable tumor in the
      retroperitoneal specimen. All 4 patients who underwent post-chemotherapy
      retroperitoneal lymph node dissection and aortic replacement after induction
      chemotherapy alone have no evidence of disease. Only 1 of the 11 patients who
      received salvage chemotherapy with or without previous post-chemotherapy
      retroperitoneal lymph node dissection have no evidence of disease. Overall 33% of
      the patients have no evidence of disease. There were no graft related
      complications. CONCLUSIONS: Aortic resection at post-chemotherapy retroperitoneal
      lymph node dissection is justified based on therapeutic benefit and morbidity.

PMID- 11342910
TI  - The natural history of lower urinary tract symptoms in black American men:
      relationships with aging, prostate size, flow rate and bothersomeness.
AB  - PURPOSE: Studies of lower urinary tract symptoms in men have been restricted to
      predominately white populations and these observations may not be generalized to
      black American men. A goal of the Flint Men's Health Study was to evaluate the
      prevalence of lower urinary tract symptoms in a community based sample of black
      American men. MATERIALS AND METHODS: We identified 721 eligible subjects after a
      2-stage stratified sampling protocol of black American men residing in Flint,
      Michigan and an in-home interview. Of these men 364 (50%) completed the study
      protocol, including serum prostate specific antigen measurement, digital rectal
      examination, uroflowmetry and transrectal ultrasound. These men comprised our
      study group. Patients completed the American Urological Association (AUA) symptom
      and bothersomeness scores. Moderate to severe symptoms and impairment were
      defined as an AUA symptom score of greater than 7 and bothersomeness score of
      greater than 3, respectively. Data were stratified by 10-year age groups.
      RESULTS: Prostate volume increased, while the peak urinary flow rate decreased
      with increasing age (p <0.001). Total AUA symptom and bothersomeness scores were
      marginally associated with age (p = 0.08 and 0.01, respectively). Although only
      8.2% of the men reported an enlarged prostate and 3% reported being on medical
      therapy for benign prostatic hyperplasia, moderate to severe lower urinary tract
      symptoms were reported by 39.6% and moderate to severe impairment was present in
      35%. CONCLUSIONS: To our knowledge this is the first study to describe the
      prevalence of lower urinary tract symptoms and its associations with age,
      prostate size and peak flow rate in a black American population. A large
      proportion of the men in this study had from moderate to severe lower urinary
      tract symptoms, of whom many were undiagnosed and untreated. The AUA symptom
      score has the potential to identify these men and its validity in black Americans
      has now been established.

PMID- 11342911
TI  - Transurethral incision compared with transurethral resection of the prostate for
      bladder outlet obstruction: a systematic review and meta-analysis of randomized
      controlled trials.
AB  - PURPOSE: Transurethral prostatic resection is the gold standard surgical
      treatment in men with lower urinary tract symptoms suggestive of bladder outlet
      obstruction but it has also been related to some risks, such as a relatively high
      rate of blood transfusion, sexual function problems and so forth. Transurethral
      prostatic incision is a simpler and less invasive procedure than transurethral
      prostatic resection. However, it is underused. We systematically reviewed all
      published randomized controlled trials comparing the effectiveness of
      transurethral prostatic incision with standard transurethral prostatic resection
      for bladder outlet obstruction and performed a meta-analysis of the available
      relevant data. MATERIALS AND METHODS: Nine randomized controlled trials comparing
      the treatment effectiveness of transurethral prostatic resection and
      transurethral prostatic incision were identified, evaluated and reviewed in a
      meta-analysis. The quality of these studies was also appraised. RESULTS: Each
      treatment achieved clear improvements in subjective and objective outcomes. The
      improvement in symptoms was equivalent 12 months postoperatively for
      transurethral prostatic incision and resection. For maximum flow rate
      transurethral prostatic resection resulted in greater improvement than
      transurethral prostatic incision. However, transurethral prostatic incision had
      several advantages over transurethral prostatic resection, such as lower
      incidence of complications, fewer blood transfusions, decreased risk of
      retrograde ejaculation, and shorter operative time and hospital stay. Also, the
      treatments had an equivalent incidence of postoperative catheterization duration
      and reoperation rate within the first 12 months. Furthermore, patients in each
      group had a similar subjective view of the treatments received. CONCLUSIONS: In
      the first 12 months after surgery transurethral prostatic incision has
      effectiveness that is equivalent to transurethral prostatic resection for
      treating patients with suspected benign prostatic obstruction who have a
      relatively small prostate. However, there is little evidence on the relative long
      term effectiveness of the 2 treatments 2 to 5 or 10 years after surgery. There is
      no clear cutoff point for prostate size that leads to good results after
      transurethral prostatic incision. A large-scale, multicenter randomized
      controlled trial is now required to evaluate comprehensively the effectiveness,
      impact on quality of life and overall cost of transurethral prostatic incision
      compared with transurethral prostatic resection.

PMID- 11342912
TI  - Long-term followup of randomized transurethral microwave thermotherapy versus
      transurethral prostatic resection study.
AB  - PURPOSE: We evaluate the durable effect of high-energy transurethral microwave
      thermotherapy and transurethral prostatic resection for treatment of patients
      with lower urinary tract symptoms suggestive of bladder outflow obstruction.
      MATERIALS AND METHODS: Between January 1996 and March 1997, 155 patients with
      lower urinary tract symptoms suggestive of bladder outflow obstruction were
      randomized to receive transurethral microwave thermotherapy (Prostatron*; device
      and commercial software) (82) or undergo transurethral prostatic resection (73).
      Initial patient evaluation was performed according to international standards.
      Patients were followed annually with the International Prostate Symptom Score (I
      PSS) and uroflowmetry (maximum flow rate). The Kaplan-Meier survival analysis was
      used to calculate the cumulative risk of re-treatment, adjusted for loss to
      followup. RESULTS: A total of 78 patients received transurethral microwave
      thermotherapy and 66 underwent transurethral prostatic resection. Median followup
      was 33 months. In the thermotherapy group mean maximum urinary flow rate improved
      from 9.2 ml. per second at baseline to 15.1, 14.5 and 11.9 ml. per second at 1, 2
      and 3 years, and mean I-PSS decreased from 20 to 8, 9, and 12, respectively. In
      the resection group the corresponding numbers for maximum urinary flow rate were
      7.8, 24.5, 23.0 and 24.7 ml. per second at 1, 2 and 3 years, and for I-PSS were
      20, 3, 4 and 3, respectively. At 36 months, 14 patients in the thermotherapy and
      8 from the resection groups underwent re-treatment, and the cumulative risk was
      19.8% (95% confidence interval 10.4% to 29.3%) and 12.9% (4.5% to 21.3%),
      respectively (p = 0.28). CONCLUSIONS: Transurethral microwave thermotherapy and
      transurethral prostatic resection achieve durable improvement in patients with
      lower urinary tract symptoms suggestive of bladder outflow obstruction, while the
      magnitude of improvement is higher with resection. The repeat thermotherapy is
      based on failure of therapy whereas repeat resection is based on complications of
      therapy.

PMID- 11342913
TI  - Predictors of patient response to antibiotic therapy for the chronic
      prostatitis/chronic pelvic pain syndrome: a prospective multicenter clinical
      trial.
AB  - PURPOSE: To our knowledge antibiotics are the most popular choice of therapy for
      all categories of the chronic prostatitis/chronic pelvic pain syndrome. We
      determine if culture, leukocyte and/or antibody status of prostate specific
      specimens predicts patient response to antibiotic therapy. MATERIALS AND METHODS:
      Patients clinically diagnosed with the chronic prostatitis/chronic pelvic pain
      syndrome according to the National Institutes of Health (NIH) definition had a
      lower urinary tract evaluation that included standard microscopy and culture of
      prostate specific specimens, and determination of the ratio of voided bladder 3
      and voided bladder 2 antibody levels against a panel of identified prostate
      pathogens (enzyme linked immunosorbent assay methodology). Symptom evaluation
      consisted of the NIH chronic prostatitis symptom index (derived) pain scale 0 to
      21, symptom severity index scale 0 to 100, symptom frequency questionnaire scale
      0 to 50 and quality of life scale 0 to 6. Patients were stratified according to
      microscopy, culture and immune status, were treated with 12 weeks of ofloxacin,
      and were assessed at 4, 12 and 24 weeks with symptom scores as well as global
      assessments. RESULTS: Based on leukocyte and culture results, 102 evaluable
      patients were stratified into categories II (14%), IIIA (48%) and IIIB (38%) of
      the chronic prostatitis/chronic pelvic pain syndrome. Of the cases 23% were
      categorized as antibody positive and 77% as antibody negative. Average age was 42
      +/- 10 years and 92% of patients were white. Of the patients 57% believed that
      they had moderate to marked improvement. All categories of the chronic
      prostatitis/chronic pelvic pain syndrome and patients in whom antibody was
      positive or negative had significant improvement in the NIH chronic prostatitis
      symptom index, symptom severity index, symptom frequency questionnaire and
      quality of life scores compared with baseline (p <0.001). There was no
      significant difference in patient response to the stratification based on
      culture, leukocyte, that is categories II, IIIA and IIIB had same beneficial
      response, or antibody status. CONCLUSIONS: Culture, leukocyte and antibody status
      of prostate specific specimens does not predict antibiotic response in patients
      with the chronic prostatitis/chronic pelvic pain syndrome. The perceived
      beneficial effect of antibiotics needs to be evaluated in a randomized placebo
      controlled trial.

PMID- 11342914
TI  - Evaluation of cold knife urethrotomy for the treatment of anastomotic stricture
      after radical retropubic prostatectomy.
AB  - PURPOSE: We evaluated the efficacy of cold knife urethrotomy for anastomotic
      stricture after radical retropubic prostatectomy. MATERIALS AND METHODS: We
      contacted all patients who underwent cold knife urethrotomy for a symptomatic
      anastomotic stricture from May 1, 1992 through January 1, 2000 at our
      institution. A control group of patients who underwent radical retropubic
      prostatectomy but did not complain of a decreased urine stream was similarly
      evaluated. Maximum urinary flow rate, post-void residual urine volume, American
      Urological Association (AUA) symptom index for benign prostatic hyperplasia, and
      continence status with a questionnaire adapted from the RAND-University of
      California-Los Angeles Prostate Cancer Index were determined in each study
      participant. RESULTS: We identified and contacted 61 patients. Complete data were
      collected on 36 of the 52 patients (59%) who agreed to participate. Mean time
      after urethrotomy was 31 months (range 1 to 77). In the control group the mean
      time after prostatectomy was 18.6 months (range 3 to 95). There was no
      statistically significant difference in the measured urinary parameters of
      maximum flow rate, post-void residual urine volume, AUA symptom index or
      continence status in the study and control groups. CONCLUSIONS: Cold knife
      urethrotomy provides a safe and effective response for the initial treatment of
      patients with anastomotic stricture after radical retropubic prostatectomy.
      Maximum urinary flow, post-void residual volume, AUA symptom score and
      perceptions of continence are similar to those in patients who underwent radical
      retropubic prostatectomy and had no complaints of a weak urine stream.

PMID- 11342915
TI  - A prospective study to evaluate the role of complexed prostate specific antigen
      and free/total prostate specific antigen ratio for the diagnosis of prostate
      cancer.
AB  - PURPOSE: Patients are increasingly undergoing prostatic biopsy to identify
      localized prostate cancer. The decision to perform a biopsy is often made on the
      basis of total prostate specific antigen (PSA). However, this value lacks
      adequate specificity for this task. We evaluate the role that a number of these
      tests, including the Bayer complexed PSA (Bayer Diagnostics, Tarrytown, New York)
      and free/total PSA ratio, may have in our clinical practice. MATERIALS AND
      METHODS: A total of 160 consecutive patients attending a prostate assessment
      clinic were enrolled during an 18-month period in our study. All patients had a
      previously recorded total PSA (range 2.6 to 20.0 ng./ml.). Before transrectal
      ultrasound biopsy of the prostate gland, a blood sample was taken with patient
      consent. The findings on ultrasound were then recorded, including prostate
      volume. Serum samples were immediately sent for subsequent storage and analysis.
      RESULTS: Of the patients enrolled 109 had benign histology while 51 had prostatic
      carcinoma. The 2 patient groups were well matched for age. In our series patients
      with prostate cancer had significantly smaller prostates and higher mean total
      PSA. At a high sensitivity, such as 95%, it appeared that Bayer complexed PSA
      performed better than the other tests and ratios, with an estimated specificity
      of 24.8% compared with 17.4% for Bayer total PSA and 15.6% for Abbott free/total
      PSA (Abbott Laboratories, Abbott Park, Illinois). Receiver operator
      characteristics curves were drawn, and when the areas under them were calculated,
      we demonstrated that the area under the curve for Bayer complexed PSA (0.706) was
      between the values for total PSA (0.671) and free/total PSA ratio (0.731).
      However, the only statistically significant improvement in performance was in
      Bayer complexed PSA over the total PSA assays. CONCLUSIONS: Our study revealed
      that the overall diagnostic performance of Bayer complexed PSA appears to be
      better than the other PSA tests and ratios studied. The use of Bayer complexed
      PSA may lead to a reduction in the number of men undergoing unnecessary prostatic
      biopsy.

PMID- 11342916
TI  - Optimal combinations of systematic sextant and laterally directed biopsies for
      the detection of prostate cancer.
AB  - PURPOSE: The standard sextant protocol for obtaining transrectal ultrasound
      guided biopsy of the prostate has been shown to underestimate the presence of
      prostate cancer. Studies have demonstrated an increased cancer detection rate
      with additional laterally directed biopsies. We compared the sensitivity of
      individual biopsy cores and evaluated combinations of these cores to identify an
      optimal biopsy strategy. MATERIALS AND METHODS: A total of 396 consecutive
      patients underwent biopsy of the lateral peripheral zone in addition to standard
      sextant biopsy. The cancer detection rate for each biopsy core was calculated.
      The sensitivity of different combinations of biopsy cores was compared with those
      of standard sextant biopsies and with a 12 core biopsy protocol that combined the
      standard sextant biopsy with a complete set of laterally directed cores. RESULTS:
      Cancer was detected in 160 of 396 (40.3%) patients. Of the possible combinations
      of biopsy cores a strategy that included laterally directed cores at the base,
      mid gland and apex of the prostate with mid lobar base and apical cores detected
      98.5% of cancers. The detection rate of this 10 core biopsy regimen was
      significantly better than that of the standard sextant protocol (p < or =0.001),
      and was equivalent to that of the 12 core regional biopsy (p > or =0.302).
      CONCLUSIONS: The standard sextant protocol failed to detect a large proportion of
      cancers located laterally in the peripheral zone. A 10 core biopsy regimen that
      combined laterally directed cores at the base, mid gland and apex of the prostate
      with mid lobar biopsy cores at the base and apex maximizes the sensitivity of
      transrectal ultrasound guided systematic biopsy.

PMID- 11342917
TI  - Prostate biopsy.

PMID- 11342918
TI  - A catalog of prostate cancer nomograms.
AB  - PURPOSE: Prediction is central to the management of prostate cancer. Nomograms
      are devices that make predictions. We organized many nomograms for prostate
      cancer. MATERIALS AND METHODS: Using MEDLINE a literature search was performed on
      prostate cancer nomograms from January 1966 to February 2000. We recorded input
      variables, prediction form, the number of patients used to develop the nomogram
      and the outcome being predicted. We also recorded the accuracy measures reported
      by the original authors and whether the nomograms have withstood validation. In
      addition, we noted whether the nomograms were proprietary or in the public
      domain. Each nomogram was classified into patient clinical disease state and the
      outcome being predicted. RESULTS: The literature search generated 42 published
      nomograms that may be applied to patients in various clinical stages of disease.
      Of the 42 nomograms only 18 had undergone validation, of which 2 partially
      failed. Few nomograms have been compared for predictive superiority and none
      appears to have been compared with clinical judgment alone. CONCLUSIONS: Patients
      with prostate cancer need accurate predictions. Prognostic nomograms are
      available for many clinical states and outcomes, and may provide the most
      accurate predictions currently available. Selection among them and progress in
      this field are hampered by the lack of comparisons for predictive accuracy.

PMID- 11342919
TI  - Predictors of biological aggressiveness of prostate specific antigen screening
      detected prostate cancer.
AB  - PURPOSE: It is not known whether screening of asymptomatic men with prostate
      specific antigen (PSA) decreases the mortality of prostate cancer. We evaluated
      the extent to which PSA screening identifies clinically significant prostate
      cancer by analyzing markers of biological aggressiveness. MATERIALS AND METHODS:
      We compared prostate cancer in 56 patients in the screening and 21 in the
      randomized control arm of a population based cohort of 8,975 men 55 to 67 years
      old participating in the Finnish arm of the European Randomized Study of
      Screening for Prostate Cancer to 47 clinically detected organ confined, 30
      clinically detected metastatic and 16 latent prostate tumors identified at
      autopsy in 46 consecutive subjects. Biological aggressiveness was determined by
      histological grading using the Gleason and Mostofi scales, tumor proliferation
      rate by Ki-67 immunostaining, p53 over expression by immunostaining and
      aneuploidy by fluorescence in situ hybridization using formalin fixed, paraffin
      embedded tumor specimens. RESULTS: A total of 56 neoplasms were detected in 2,781
      men (2%) who participated in PSA screening and 21 were detected in 5,975
      nonscreened controls (0.35%) during the study period. Disease in nonscreened
      controls more often involved a high tumor proliferation rate (p = 0.004) and p53
      over expression (p = 0.015) than screening detected disease. At least 1 feature
      of biological aggressiveness was present in 19% of latent, 34% of screening
      detected, 51% of clinically detected and organ confined, 62% of randomized
      control and 87% of metastasis cases. Of the screening detected tumors defined as
      biologically aggressive 74% were identified at organ confined stages pT1-2N0M0.
      CONCLUSIONS: PSA screening detects a significant number of biologically
      aggressive cancers at an early clinical stage, implying that screening may
      decrease mortality.

PMID- 11342920
TI  - Systematic transperineal ultrasound guided template biopsy of the prostate in
      patients at high risk.
AB  - PURPOSE: A negative biopsy result does not necessarily equate with cancer in
      specific high risk groups. We describe an alternative systematic biopsy technique
      for evaluating this subgroup of patients. MATERIALS AND METHODS: From March 1997
      to May 1999 a total of 88 men underwent systematic ultrasound guided biopsy using
      the transperineal template technique. All patients had undergone at least 1 and
      75 (85%) had undergone 2 or more previous sets of biopsies. In addition, study
      inclusion required high risk parameters, including prostate specific antigen
      (PSA) velocity greater than 0.75 ng./ml., PSA greater than 10 ng./ml. or previous
      prostatic intraepithelial neoplasia on biopsy, and/or atypical small cell acinar
      proliferation. RESULTS: Cancer was identified in 38 of the 88 men (43%) in this
      high risk subgroup undergoing repeat biopsy. A mean of 15.1 previous biopsy cores
      had been obtained. The most common biopsy grade was 6 (range 4 to 9).
      Adenocarcinoma was identified in the transition zone area in 29 of 38 cases
      (76%), including 15 (39%) in which disease was detected in the transition zone
      only. Persistent PSA acceleration greater than 0.75 ng./ml. was the major
      indicator for transperineal template biopsy in 83 of the 88 patients (94%). The
      only significant independent variable predictive of positive biopsy was prostate
      volume. Mean prostate volume in the positive and negative biopsy groups was 48
      and 73 gm., respectively (p <0.001). Complications were rare and self-limiting,
      consisting primarily of hematuria and urinary retention requiring overnight
      catheterization in 2 patients. CONCLUSIONS: Systematic transperineal template
      biopsy of the prostate is a safe and precise repeat biopsy technique in patients
      who remain at high risk for adenocarcinoma.

PMID- 11342921
TI  - The efficacy of transurethral biopsy for predicting the long-term clinical impact
      of prostatic invasive bladder cancer.
AB  - PURPOSE: Involvement of the prostate by bladder cancer directly impacts survival,
      the risk of urethral recurrence, and treatment decisions concerning the timing of
      cystectomy and type of urinary diversion. Transurethral lateromontanal loop
      biopsies are proposed as the most accurate method for evaluating the prostatic
      urethra. Due to the potential clinical impact on individuals we assessed its
      accuracy in a large cohort. MATERIALS AND METHODS: Transurethral lateromontanal
      loop biopsies were performed in 246 of 416 male patients at our institution
      between 1989 and 1997. The predictive value and sensitivity of transurethral
      biopsy, patterns of recurrence, survival and clinical impact were assessed in a
      cohort with 10 years of followup. RESULTS: The sensitivity of transurethral
      biopsy for prostatic stromal invasion was 53%, specificity was 77%, positive
      predictive value was 45% and negative predictive value was 82%. At the 10-year
      followup 129 patients (52.4%) were dead, 85 (32%) had no evidence of disease, 16
      (6.5%) had disease and 16 (6.5%) were lost to followup. Mean followup in patients
      at risk for urethral recurrence was 61.7 months (range 0.56 to 134.1, median
      56.8). Delayed urethrectomy was performed in 15 of 235 cases (6.4%) at a mean of
      15.2 months. Of the 246 patients 99 had prostatic disease at transurethral biopsy
      and/or cystectomy, including 11 (11%) with urethral recurrence. No patient
      required continent diversion takedown or died of urethral recurrence.
      CONCLUSIONS: Transurethral biopsy did not accurately determine prostatic
      involvement. Prostatic involvement at biopsy or cystectomy translated into a
      higher risk of urethral recurrence. However, it did not have significant clinical
      impact or affect survival and should not be an absolute contraindication to
      urethral diversion.

PMID- 11342923
TI  - Radioactive implant migration in patients treated for localized prostate cancer
      with interstitial brachytherapy.
AB  - PURPOSE: In several of the initial patients undergoing brachytherapy at our
      institution radioactive implants were visible in the thorax on chest radiography.
      The clinical ramifications of this unanticipated finding were unclear. Thus, we
      investigated the incidence of brachytherapy seed migration to the chest and
      whether these seeds were associated with any clinical significance. MATERIALS AND
      METHODS: We retrospectively reviewed the records of all patients who underwent
      ultrasound or computerized tomography guided brachytherapy of 103palladium seeds
      from March 1997 to March 1999. This list of patients on brachytherapy was then
      matched against the radiology computer system to determine those who had
      undergone chest X-ray after brachytherapy. When the radiology report was unclear
      regarding brachytherapy seeds, chest x-rays were reviewed by one of us (R. O.) to
      determine the presence and position of the seeds. RESULTS: Post-brachytherapy
      chest x-rays were available in 110 of the 183 patients. In 78 cases no
      brachytherapy seeds were identified. Radioactive implants were identified on
      chest radiography in 32 patients (29%), including 1 to 5 seeds in 20, 8, 1, 2 and
      1, respectively. No patients complained of any change in pulmonary symptoms after
      brachytherapy. CONCLUSIONS: Radioactive implants migrated after brachytherapy for
      localized prostate cancer in 29% of the patients who underwent post-procedure
      radiography. There did not appear to be a pattern to the seed distribution.
      However, while the incidence was not negligible, no patient appeared to have any
      acute pulmonary symptoms. Therefore, while the migration of radioactive implants
      to the chest is a real phenomenon, it appears to have no adverse clinical
      consequences in the early post-procedure period.

PMID- 11342922
TI  - The gonadotropin-releasing hormone antagonist abarelix depot versus luteinizing
      hormone releasing hormone agonists leuprolide or goserelin: initial results of
      endocrinological and biochemical efficacies in patients with prostate cancer.
AB  - PURPOSE: We contrasted the endocrinological and biochemical efficacies of
      abarelix depot, a pure gonadotropin-releasing hormone antagonist, with a
      prospective concurrent control cohort receiving luteinizing hormone releasing
      hormone (LH-RH) agonists with or without antiandrogen for treatment of patients
      with prostate cancer receiving initial hormonal therapy. MATERIALS AND METHODS:
      In this phase 2 open label study 242 patients with prostate cancer requiring
      initial hormonal treatment received abarelix depot (209) or LH-RH agonists (33)
      with or without antiandrogen. A total of 100 mg. abarelix depot was delivered
      intramuscularly every 28 days with an additional injection on day 15. LH-RH
      agonists with or without antiandrogen were administered according to the depot
      formulation used. Endocrine efficacy was measured by the absence of testosterone
      surge and rapidity of castration onset. The rate of prostate specific antigen
      decrease was assessed. RESULTS: No patient treated with abarelix depot had
      testosterone surge during week 1 compared with 82% of those treated with LH-RH
      agonists. The concomitant administration of antiandrogen had no effect. During
      the first week of drug administration, in 75% of patients treated with abarelix
      depot and in 0% of those treated with LH-RH agonist medical castration was
      achieved. Prostate specific antigen decrease was faster, with no flare or surge
      in patients treated with abarelix depot. Abarelix depot was well tolerated.
      CONCLUSIONS: Abarelix depot represents a new class of hormonal therapy,
      gonadotropin releasing hormone antagonists, that has rapid medical castration and
      avoids the testosterone surge characteristic of LH-RH agonists.

PMID- 11342924
TI  - The stone cone: a new generation of basketry.
AB  - PURPOSE: We designed a device to minimize ureteral stone migration during
      intracorporeal lithotripsy, decrease the likelihood of stone and/or basket
      entrapment, and extract whole stones and fragments. MATERIALS AND METHODS:
      Nitinol and stainless steel wires were configured into expandable tapered cones,
      which were placed cephalad to in vitro and in vivo concretions, and used to trap
      and extract stones as well as other test material. Safety features were evaluated
      by measuring the release of ball bearings and the tension needed to unwind the
      coils of the cone, which were greater than 4 mm. in diameter. We treated 4
      patients with ureteral calculi using the Stone Conedagger to prevent migration
      and extract fragments. RESULTS: The cone-shaped devices expanded to occlude the
      test devices and human ureters, and prevented stone migration. They extracted
      whole concretions and fragments greater than 1.5 mm. The cone-shaped basket
      released a 5.5 mm. ball bearing at an average 0.127 pounds of tension when pulled
      through a 5 mm. plastic orifice. Coils greater than 4 mm. in diameter were
      straightened at a tension of 0.10 to 0.14 pounds. Stone migration during
      intracorporeal lithotripsy was prevented in the 4 patients with ureteral calculi,
      in whom large and small fragments were safely extracted. CONCLUSIONS: The Stone
      Cone may be placed via a ureteral catheter and opened cephalad to a ureteral
      stone to prevent stone migration during intracorporeal lithotripsy. It may
      extract whole stones and fragments greater than 1.5 mm. It is designed, so that
      its coils greater than 4 mm. in diameter release concretions too wide for the
      ureter or ureteral orifice after approximately 0.127 pounds of tension are
      applied. Because of these features, the Stone Cone represents a new generation of
      basketry appropriate to the era of ureteroscopy and intracorporeal lithotripsy.
      It is worthy of further clinical study.

PMID- 11342925
TI  - Pubovaginal sling surgery for simple stress urinary incontinence: analysis by an
      outcome score.
AB  - PURPOSE: We assessed the results of pubovaginal sling surgery in women with
      simple stress urinary incontinence using strict subjective and objective
      criteria. MATERIALS AND METHODS: Simple incontinence was defined as sphincteric
      incontinence with no concomitant urge incontinence, pipe stem or fixed scarred
      urethra, urethral or vesicovaginal fistula, urethral diverticulum, grade 3 or 4
      cystocele, or neurogenic bladder. A total of 67 consecutive women with a mean age
      plus or minus standard deviation of 56 +/- 11 years who underwent pubovaginal
      sling surgery for simple sphincteric incontinence were prospectively followed for
      12 to 60 months (mean 33.9 +/- 22.2). Treatment outcomes were classified
      according to a new outcome score. Cure was defined as no urinary loss due to urge
      or stress incontinence, as documented by 24-hour diary and pad test, with the
      patient considering herself cured. Failure was defined as poor objective results
      with the patient considering surgery to have failed. Cases that did not fulfill
      these cure-failure criteria were considered improved and further classified into
      a good, fair or poor response. RESULTS: Of the 67 patients 46 (69%) had type II
      and 21 (31%) had type III incontinence. Preoperative diary and pad tests revealed
      a mean of 5.9 +/- 3.6 stress incontinence episodes and a mean urinary loss of
      91.8 +/- 81.9 gm. per 24 hours. There were no major intraoperative, perioperative
      or postoperative complications. Two patients (3%) had persistent minimal stress
      incontinence and 7 (10%) had new onset urge incontinence within 1 year after
      surgery. Overall using the strict criteria of our outcome score 67% of the cases
      were classified as cured and the remaining 33% were classified as improved. The
      degree of improvement was defined as a good, fair and poor response in 21%, 9%
      and 3% of patients, respectively. CONCLUSIONS: Mid-term outcome results defined
      by strict subjective and objective criteria confirm that the pubovaginal sling is
      highly effective and safe surgery for simple sphincteric incontinence. A followup
      of more than 5 years is required to establish the long-term durability of this
      procedure.

PMID- 11342926
TI  - A prospective evaluation of the efficiency of early postoperative bladder
      emptying after the Stamey procedure or pubovaginal sling for stress urinary
      incontinence.
AB  - PURPOSE: The pubovaginal sling has been criticized as having a higher incidence
      of postoperative voiding dysfunction than other surgical approaches for the
      management of stress urinary incontinence. In 2 similar patient groups we
      prospectively compared the rates of early postoperative voiding dysfunction after
      the pubovaginal sling or Stamey procedure. MATERIALS AND METHODS: Between June
      1995 and January 1997, 50 consecutive patients underwent the pubovaginal sling or
      Stamey procedure. Emptying efficiency was measured 48 hours postoperatively by
      suprapubic catheter in the Stamey group and intermittent catheterization in the
      pubovaginal sling group. When emptying efficiency was greater than 75%,
      intermittent catheterization was stopped or the suprapubic catheter was removed.
      RESULTS: There was no statistically significant difference in emptying efficiency
      for the first 3 voids using the Dunn multiple comparison method. Median voiding
      efficiencies were 37%, 43% and 61% with the Stamey procedure in group 1 (mean
      43%, 45% and 54%), and 60%, 75% and 75% with the pubovaginal sling in group 2
      (mean 49%, 68% and 69%), respectively. The mean number of intermittent
      catheterizations performed in patients with the pubovaginal sling was 5.7 in less
      than 1 day. In the Stamey group the suprapubic catheter was removed an average of
      6 days postoperatively. The mean duration of hospital stay was similar for the
      sling and Stamey groups (5.4 versus 6 days, respectively). There were 2 patients
      in each group who were voiding inefficiently after day 7. Voiding efficiency was
      restored at 53 and 86 days in the 2 patients with slings and at 18 days in 1 of
      the 2 who underwent the Stamey procedure, respectively. The second patient who
      underwent the Stamey procedure was able to void without using the catheter at
      all, and it was removed 30 days postoperatively when emptying efficiency was
      confirmed greater than 75%. CONCLUSIONS: These data show that early postoperative
      voiding dysfunction, measured using bladder emptying efficiency, after the
      pubovaginal sling is no more common than after the Stamey procedure and help
      justify the broadened indications for pubovaginal sling for treatment of stress
      urinary incontinence.

PMID- 11342927
TI  - Pubovaginal sling using cadaveric fascia and bone anchors: disappointing early
      results.
AB  - PURPOSE: Pubovaginal sling procedures offer highly effective treatment for
      patients with female stress urinary incontinence. A recent modification of this
      technique is the use of cadaveric fascia lata as a sling material supported with
      titanium anchors placed bilaterally in the pubic bone. We reviewed our experience
      with this procedure and assessed our outcome. MATERIALS AND METHODS: A total of
      154 consecutive patients underwent a bone anchored, cadaveric fascia pubovaginal
      sling procedure by a single surgeon from July 1998 to June 1999. All patients
      were evaluated preoperatively with a detailed history, pelvic examination and
      radiographic or multichannel video urodynamic studies to diagnose stress urinary
      incontinence. Our technique begins with the nonincision placement of titanium
      bone anchors transvaginally into the pubic bone bilaterally. A 2 cm. wide tunnel
      is created bluntly beneath the vaginal epithelium between the 2 puncture sites
      with a right angle clamp. A 2 x 7 cm. strip of cadaveric fascia is then passed
      through the tunnel, into the retropubic space and secured to 2-0 polypropylene
      sutures attached to the anchors. After securing the sling, the transvaginal
      puncture sites are closed with 2-0 polyglactin sutures. Patients were seen
      postoperatively at 6 weeks, and 3 and 6-month followup. Patient age averaged 60
      years (range 38 to 85), with an overall average length of followup from surgery
      of 10.6 months (range 6 to 16). All patients were mailed a self-administered
      questionnaire and participated in a telephone interview with an office nurse to
      retrospectively assess outcome and evaluate for recurrent stress urinary
      incontinence. Recurrent stress urinary incontinence was graded as 0-none, 1-rare,
      2-moderate and 3-severe. Repeat pubovaginal sling procedure that was performed in
      patients with grades 2 to 3 stress urinary incontinence was considered a failure
      for the purpose of our study. RESULTS: Of all 154 patients 58 (37.6%) had
      recurrent moderate to severe (grades 2 to 3) stress urinary incontinence at
      followup. A total of 26 patients underwent a second pubovaginal sling procedure
      for a reoperation rate of 16.9%. Intraoperative findings at reoperation revealed
      the titanium anchors to be in position, the polypropylene sutures to be intact,
      and retropubic fibrosis and scarring of the urethropelvic ligament suggesting
      appropriate retropubic placement of the sling in all cases. Uniformly all
      allogenic cadaveric fascia used for sling material appeared to be fragmented,
      attenuated or simply absent. Average time to reoperation was 9 months (range 3 to
      15). CONCLUSIONS: Early results using a bone anchored cadaveric fascia
      pubovaginal sling procedure were discouraging. Based on findings at reoperation,
      we attribute this result to the failure of our sling material and have abandoned
      the use of cadaveric fascia allografts in all pubovaginal slings at our
      institution.

PMID- 11342928
TI  - Female stress incontinence.

PMID- 11342929
TI  - The Ehlers-Danlos syndrome presenting with flank pain.

PMID- 11342930
TI  - Spontaneous shunt between the superior mesenteric vein and the right renal vein
      caused by portal hypertension.

PMID- 11342931
TI  - Antibody induced coagulopathy from bovine thrombin use during partial
      nephrectomy.

PMID- 11342932
TI  - Post-transplant lymphoproliferative disorder presenting as a large tumor of the
      renal allograft.

PMID- 11342933
TI  - Perirenal myelolipoma causing giant, infected hydronephrosis and renal pelvic
      stone.

PMID- 11342934
TI  - Incidental cystic, partially differentiated nephroblastoma in an adult.

PMID- 11342935
TI  - Parenchymal sparing surgery in a patient with multiple bilateral papillary renal
      cancer.

PMID- 11342936
TI  - Laparoscopic assisted autotransplantation for treatment of transitional cell
      carcinoma of the mid ureter.

PMID- 11342937
TI  - Ureteral fibroepithelial polyp prolapsed into the bladder cavity suspending a
      bladder stone.

PMID- 11342938
TI  - Tripe palms and malignant acanthosis nigricans: cutaneous signs of imminent
      metastasis in bladder cancer?

PMID- 11342939
TI  - Regression of metastatic transitional cell carcinoma in response to tamoxifen.

PMID- 11342940
TI  - Intracavernosal phenylephrine for recurrent priapism: self-administration by drug
      delivery implant.

PMID- 11342941
TI  - Positron emission tomography detection of metastatic penile squamous cell
      carcinoma.

PMID- 11342942
TI  - Development of seminoma following conservative treatment of testicular epidermoid
      cyst.

PMID- 11342943
TI  - Scrotal metastasis from ureteral cancer.

PMID- 11342944
TI  - Urological medical malpractice.
AB  - PURPOSE: Like all other medical and surgical practitioners, urologists are
      occasionally confronted with the unpleasant realization that they are being sued
      for medical malpractice. These suits are generated through any number of acts or
      failures to act during innumerable circumstances. We reviewed all urological
      claims presented to 1 representative insurance company and delineated the types
      of acts, settings, expenses and disposition of these claims. This review was
      performed to understand better the claims confronting urologists and provide
      future guidance to urologists in the medical malpractice setting. METHODS AND
      MATERIALS: Working with The St. Paul Companies 259 medical malpractice claims
      against urologists consecutively closed from 1995 to 1999 were reviewed. Claims
      were defined as urological malpractice when the insured-defendant in a
      malpractice claim was a urologist. Each claim was reviewed in terms of
      disposition, patient age, geographic location, office-hospital setting, purported
      negligent act, procedure if applicable, litigation status and expenses incurred.
      Data ascertained were then compared to national practice statistics provided by
      the American Urological Association (AUA) and American Medical Association. In
      addition, a literature search with the key words urology and malpractice was
      performed. Related pertinent documents were reviewed and incorporated into this
      analysis. RESULTS: We reviewed 259 urological medical malpractice claims closed
      between 1995 and 1999. During this period The St. Paul Companies insured various
      numbers of private practice urologists. In the years ending 1995 to 1999, 489,
      492, 438, 377 and 426 individual urologists, respectively, were insured with
      respective premiums paid in the amounts of $6.27, $6.23, $5.80, $5.15 and $3.87
      million. Claims were analyzed by AUA section. The greatest incidence of claims
      occurred in the Southeastern section, followed by the North Central, South
      Central, Mid-Atlantic, New England, Western and New York sections. According to
      AUA statistics the greatest number of practicing urologists are in the
      Southeastern section, followed by the Western, North Central, South Central, Mid
      Atlantic, New York, New England and Northeastern sections. When analyzing average
      expenses, the New England section had the most costly claims, followed by the Mid
      Atlantic, North Central, Southeastern, South Central, Western and New York
      sections with respective mean expenses of $266,887, $145,031, $47,667, $41,843,
      $38,365, $30,037 and $1,065 per claim, respectively. The greatest percent of
      claims arose from the categories of inpatient, adult and surgical procedures.
      Endourological procedures resulted in the greatest incidence of surgical claims.
      However, claims related to prostatectomy involved the most expensive claims with
      a mean cost of $185,345. Of the surgical procedures incidents defined as
      postoperative complications were the most common acts of negligence generating a
      malpractice claim. The majority of malpractice claims were filed in court but
      subsequently voluntarily dismissed by the plaintiff. CONCLUSIONS: Medical
      malpractice persists as an issue confronting urologists. Urologists must strive
      to maintain open, honest, in-depth communications with their patients when
      occurrences with potential malpractice overtones arise.

PMID- 11342946
TI  - Re: Influence of tumor stage, size, grade, vascular involvement, histological
      cell type and histological pattern on multifocality of renal cell carcinoma.

PMID- 11342947
TI  - Lamina muscularis propria thickness of renal pelvis predicts radiological outcome
      of surgical correction of ureteropelvic junction obstruction.
AB  - PURPOSE: We examine if there is a relationship between the histopathology of the
      renal pelvis and postoperative radiological findings in children with
      ureteropelvic junction obstruction. MATERIALS AND METHODS: The records of 220
      patients who underwent pyeloplasty for isolated ureteropelvic junction
      obstruction between 1988 and 1996 were retrospectively reviewed, and 41 (42
      kidneys) were identified who had adequate histological specimens and
      postoperative radiographic studies (ultrasonography and/or well tempered
      renogram) for examination. Histological features of the lamina muscularis propria
      from the renal pelvis were correlated with the radiographic outcome after
      pyeloplasty. RESULTS: Lamina muscularis propria thickness of the renal pelvis
      correlated significantly with radiological improvement. All kidneys with renal
      pelvic lamina muscularis propria thickness less than 250 microm. showed
      radiological improvement at 3 to 6 months postoperatively, those with thickness
      between 250 and 350 microm. had improvement at 9 months and those with lamina
      thickness greater than 350 microm. had a significantly worse outcome at all
      observation points. At 3 and 6 months postoperatively 16 of 30 (53%) and 23 of 34
      (68%) children with radiological improvement had a mean lamina muscularis propria
      thickness of 252 +/- 131.5 microm. and 263 +/- 122.8 microm., respectively, while
      the remaining unimproved 14 and 12 patients had a mean thickness of 374 +/- 64.3
      microm. (p <0.01) 372 +/- 66.1 microm. (p <0.05), respectively. CONCLUSIONS: The
      lamina muscularis propria thickness of the renal pelvic wall can provide insight
      to the expected time of postoperative improvement on radiological studies in
      children with ureteropelvic junction obstruction.

PMID- 11342948
TI  - The pelvic plexus and antireflux surgery: topographical findings and clinical
      consequences.
AB  - PURPOSE: Voiding dysfunction and urinary retention are rare complications of
      antireflux surgery. As mainly reported after bilateral antireflux surgery with
      extravesical technique, bladder insufficiency has been suspected to be caused by
      intraoperative damage to neural structures. We studied the topography of the
      pelvic plexus and assessed the injury to the plexus resulting from antireflux
      surgery. MATERIALS AND METHODS: Human cadavers fixed with Thiel solution were
      used for dissection. The superior hypogastric plexus and hypogastric nerves were
      identified as the pathway to the pelvic plexus. After dissecting the surrounding
      fatty tissue the S2 to S4 nerves and efferent nerve bundles from the pelvic
      plexus were identified. RESULTS: The main portion of the pelvic plexus was
      located about 1.5 cm. dorsal and medial to the ureterovesical junction. The
      bundles of the pelvic plexus ended at the distal ureter, trigone and rectum. When
      simulating an antireflux procedure, there was a high risk of injury to the pelvic
      plexus and its efferent nerves if dissection was performed distal to the ureter
      and dorsal trigone. CONCLUSIONS: Careful dissection close to the ureter avoids
      inadvertent injury to the pelvic plexus. To minimize the risk of voiding
      dysfunction bilateral antireflux surgery should be performed at 2 sessions unless
      the operative technique allows preservation of the neural structures.

PMID- 11342949
TI  - The newborn exstrophy bladder inadequate for primary closure: evaluation,
      management and outcome.
AB  - PURPOSE: The surgical approach to the small newborn exstrophy bladder inadequate
      for primary closure remains undetermined. Various methods for long-term
      management have been implemented. We evaluated our experience with late primary
      closure of the small exstrophied bladder template. MATERIALS AND METHODS: Our
      institutional database of patients treated and followed for the exstrophy
      epispadias complex was reviewed. Of these patients 19 had a bladder template that
      was too small to close in the newborn period. The treatment and outcome of these
      19 patients were reviewed. RESULTS: Of the 19 children who had delayed closure
      due to a small bladder template 14 were males and 5 were females. Followup from
      birth ranged from 2 to 36 years (mean 18 years). Primary closure was performed at
      a mean patient age of 13 months (range 6 months to 2 years). Pelvic osteotomy was
      performed in 16 patients. Of the 19 patients 9 achieved continence after gaining
      a bladder capacity sufficient for bladder neck reconstruction, 4 required
      enterocystoplasty to augment bladder volume and perform clean intermittent
      catheterization (2 per stoma and 2 per urethra), 1 required a colon conduit for
      an extremely small bladder, and 1 underwent cystectomy and ureterosigmoidostomy
      for rhabdomyosarcoma. Four patients are currently incontinent, including 3 who
      are awaiting bladder neck reconstruction and 1 who has frequent nighttime
      incontinence that is medically managed. CONCLUSIONS: Delayed primary closure of
      the small bladder exstrophy template can allow the native bladder tissue adequate
      time to grow to a size feasible for successful closure. Epispadias repair can
      usually be performed at the same time and is facilitated by prior testosterone
      administration. Bladder neck reconstructive techniques have achieved continence
      without the need for augmentation or bladder replacement in 47% of the patients
      in our series. For patients who do not achieve adequate capacity for bladder neck
      reconstruction, preservation of the native bladder template facilitates future
      augmentation and ureteral reimplantation, thus requiring use of less bowel in the
      growing child.

PMID- 11342950
TI  - Pelvic fracture urethral injuries in girls.
AB  - PURPOSE: Injuries to the female urethra associated with pelvic fracture are
      uncommon. They may vary from urethral contusion to partial or circumferential
      rupture. When disruption has occurred at the level of the proximal urethra, it is
      usually complete and often associated with vaginal laceration. We retrospectively
      reviewed the records of a series of girls with pelvic fracture urethral stricture
      and present surgical treatment to restore urethral continuity and the outcome.
      MATERIALS AND METHODS: Between 1984 and 1997, 8 girls 4 to 16 years old (median
      age 9.6) with urethral injuries associated with pelvic fracture were treated at
      our institutions. Immediate therapy involved suprapubic cystostomy in 4 cases,
      urethral catheter alignment and simultaneous suprapubic cystostomy in 3, and
      primary suturing of the urethra, bladder neck and vagina in 1. Delayed 1-stage
      anastomotic repair was performed in 1 patient with urethral avulsion at the level
      of the bladder neck and in 5 with a proximal urethral distraction defect, while a
      neourethra was constructed from the anterior vaginal wall in a 2-stage procedure
      in 1 with mid urethral avulsion. Concomitant vaginal rupture in 7 cases was
      treated at delayed urethral reconstruction in 5 and by primary repair in 2. The
      surgical approach was retropubic in 3 cases, vaginal-retropubic in 1 and vaginal
      transpubic in 4. Associated injuries included rectal injury in 3 girls and
      bladder neck laceration in 4. Overall postoperative followup was 6 months to 6.3
      years (median 3 years). RESULTS: Urethral obliteration developed in all patients
      treated with suprapubic cystostomy and simultaneous urethral realignment. The
      stricture-free rate for 1-stage anastomotic repair and substitution urethroplasty
      was 100%. In 1 girl complete urinary incontinence developed, while another has
      mild stress incontinence. Retrospectively the 2 incontinent girls had had an
      associated bladder neck injury at the initial trauma. Two recurrent vaginal
      strictures were treated successfully with additional transpositions of lateral
      labial flaps. CONCLUSIONS: This study emphasizes that combined vaginal-partial
      transpubic access is a reliable approach for resolving complex obliterative
      urethral strictures and associated urethrovaginal fistulas or severe bladder neck
      damage after traumatic pelvic fracture injury in female pediatric patients.
      Although our experience with the initial management of these injuries is limited,
      we advocate early cystostomy drainage and deferred surgical reconstruction when
      life threatening clinical conditions are present or extensive traumatized tissue
      in the affected area precludes immediate ideal surgical repair.

PMID- 11342951
TI  - Collagen injection for treatment of urinary incontinence in children.
AB  - PURPOSE: We assess the success rate of periurethral collagen injection in
      children with neurogenic bladder dysfunction secondary to myelomeningocele.
      MATERIALS AND METHODS: From 1992 to 1998, 15 male and 5 female patients with
      spina bifida (age 13.3 +/- 3.8 years) underwent endoscopic collagen injection for
      the treatment of urinary incontinence secondary to sphincter deficiency. Mean
      followup was 4.2 years. Pretreatment urodynamic study showed a stable compliant
      bladder with an average leak point pressure of 52 cm. H2O (range 23 to 100).
      Concurrent medical management included anticholinergics in 15 cases, agonists in
      3, and clean intermittent catheterization in 16. Five patients had undergone
      previous ileocystoplasty. RESULTS: Collagen injections were given with the
      patient under general anesthesia. The number of injections was 1 in 5 cases, 2 in
      11, 3 in 3, and 4 in 1. Average collagen volume injected per treatment was 6.6 cc
      (range 2 to 13). All patients were evaluated on a subjective continence scale of
      no change (wet), improved or completely dry at the time of assessment. Of the 20
      patients, 16 had no change, 3 showed improvement and 1 was dry. Initial
      improvement in the first 2 months after injection deteriorated thereafter in 16
      cases. CONCLUSIONS: The previously reported high success rate of collagen
      injection is not supported by this study. With long-term followup collagen
      injection is rarely effective for treating urinary incontinence in children with
      neurogenic sphincter deficiency.

PMID- 11342952
TI  - A prospective randomized clinical trial to evaluate methods of postoperative care
      of hypospadias.
AB  - PURPOSE: Hypospadias repair is a common operation performed by pediatric
      urologists. Perhaps the greatest variable and source of controversy of
      postoperative care is the surgical dressing. We hypothesized that using no
      dressing would achieve surgically comparable results to those traditionally
      achieved by a postoperative dressing and it would also simplify postoperative
      parent delivered home care. Accordingly we designed a prospective randomized
      clinical trial to compare surgical outcome and postoperative care after
      hypospadias repair in boys with no dressing and those who received 1 of the 2
      most common types of dressing. MATERIALS AND METHODS: In a 12-month period 120
      boys with an average age of 2.2 years underwent primary 1-stage hypospadias
      repair at a single center with 4 participating surgeons. Repair was performed in
      60 boys with proximal and 60 with distal hypospadias on an outpatient basis.
      Ethics and Internal Review Board approval, and informed consent were obtained.
      Boys were then prospectively randomized to receive no dressing, an adhesive
      biomembrane dressing or a compressive wrap dressing. Comprehensive instructions
      on postoperative care were distributed to all families and a questionnaire was
      distributed to the parents at the initial followup. Surgical outcome was
      evaluated and questionnaire responses were analyzed. Fisher's exact test was done
      to test the significance of differences in surgical outcomes and questionnaire
      responses. RESULTS: A total of 117 boys completed the prospective randomized
      trial. Surgical staff withdrew 3 cases from randomized selection to place a
      dressing for postoperative hemostasis. We obtained 101 questionnaires for
      response analysis. The type or absence of the dressing did not correlate with the
      need for repeat procedures, urethrocutaneous fistula, or meatal stenosis or
      regression. Analysis revealed less narcotic use in the no dressing group and
      fewer telephone calls to the urology nurse, or on-call resident and/or fellow.
      These findings were statistically significant. In addition, there were more
      unscheduled visits to the urology clinic, emergency room or primary physician
      office by boys with than without a dressing. Furthermore, 29% of the parents were
      not psychologically prepared to remove the dressing and 12% were so reluctant
      that the dressing was removed at the urology outpatient clinic. CONCLUSIONS: The
      surgical outcome and rate of adverse events or complications were not compromised
      without a postoperative dressing. An absent dressing simplified postoperative
      ambulatory parent delivered home care. We recommend that dressings should be
      omitted from routine use after hypospadias repair.

PMID- 11342953
TI  - Leydig insulin-like hormone, gubernacular development and testicular descent.
AB  - PURPOSE: Testicular descent is controlled by 2 morphological and hormonal steps.
      Transabdominal testicular descent is mediated by gubernacular swelling and
      regression of the cranial suspensory ligament. Mullerian inhibiting substance
      (MIS) has been proposed to stimulate the swelling but this remains controversial.
      Recently, a mouse mutant for Leydig insulin-like hormone (Insl3) was found to
      have undescended testis and deficient gubernaculum. We examine the testicular
      position of Insl3 mutant mice and the development of gubernacula. MATERIALS AND
      METHODS: Mice with Insl3 homozygotes (-/-), heterozygotes (+/-) and wild-types
      (+/+) were examined at embryonic day 16.5 and birth. Macroscopic dissections and
      measurements of the testicular position, as well as microscopic analysis
      (hematoxylin and eosin, and Masson's trichrome) were performed. RESULTS: Of the
      mice 11 Insl3 homozygote males had significantly impaired testicular descent at
      embryonic day 16.5 and birth (p <0.01), and the cord was thin and elongated,
      while 14 heterozygotes and 7 wild-types had normal testicular descent.
      Microscopically, the gubernaculum of Insl3 homozygotes was small with some muscle
      development but no central core of mesenchyme at embryonic day 16.5. On the other
      hand, heterozygotes and wild-types had normal gubernacular development with a
      swelling reaction. CONCLUSIONS: Insl3 mutants show feminized gubernaculum with
      deficient mesenchymal core. Insl3 appears to have some role in the gubernacular
      swelling reaction in mice.

PMID- 11342954
TI  - Primary prostatic leiomyosarcoma.

PMID- 11342955
TI  - Implications of prenatal ultrasound screening in the incidence of major
      genitourinary malformations.
AB  - PURPOSE: During the last 3 decades infant mortality has decreased nearly 50%.
      While neonatal intensive care deserves much of the credit, the recent increase in
      prenatal ultrasound from 33% of pregnancies in 1980 to 78% in 1987 has improved
      early detection. We evaluate the impact of prenatal ultrasound on major
      genitourinary malformations. MATERIALS AND METHODS: Data obtained from the
      Malformations Surveillance Program at Brigham and Women's Hospital between 1974
      and 1994 tracked 163,431 pregnancies and termination rates of fetuses with spina
      bifida, bladder exstrophy, the prune belly syndrome and posterior urethral
      valves. RESULTS: Hospital data revealed that pregnancy was electively terminated
      due to spina bifida in 65% of cases, posterior urethral valves in 46%, the prune
      belly syndrome in 31% and exstrophy in 25%. CONCLUSIONS: Clearly, surveillance
      programs and improved accuracy of prenatal ultrasound have allowed early
      diagnosis of major genitourinary malformations. Many factors influence decision
      making in these affected fetal cases, including the financial and emotional
      impact of these major anomalies during lifetime. Future societal decisions and
      reduction in these anomalies may influence our training programs, manpower needs,
      medical facility requirements and character of our practices. These findings may
      have significant implications in the field of pediatric urology.

PMID- 11342956
TI  - Expression of inter-alpha inhibitor related proteins in kidneys and urine of
      hyperoxaluric rats.
AB  - PURPOSE: To investigate the involvement of the inter-alpha inhibitor family of
      proteins in calcium oxalate stone formation we determined immunohistochemical
      distribution in the kidneys and excretion in the urine of these proteins in
      normal and hyperoxaluric rats. Various members of the family have been shown to
      inhibit the formation and retention of calcium oxalate crystals in the kidneys.
      MATERIALS AND METHODS: Hyperoxaluria was induced in male Sprague-Dawley rats by
      administering 0.75% ethylene glycol. The inter-alpha inhibitor family consists of
      inter-alpha inhibitor, pre-alpha inhibitor, the so-called heavy chains H1, H2 and
      H3, and the light chain bikunin. Antibodies against these molecules were used to
      localize various proteins in rat kidneys by immunohistochemical techniques. Urine
      was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and
      Western blot analysis to determine the expression of various members of the inter
      alpha inhibitor family. RESULTS: In normal kidneys staining for inter-alpha
      inhibitor and other members of the family was mostly limited to the proximal
      tubules and generally to their luminal contents. Eight weeks after the induction
      of hyperoxaluria various sections of renal tubules stained positive for inter
      alpha inhibitor, bikunin and H3. Positive staining was observed in the tubular
      lumina as well as in the cytoplasm of epithelial cells. Crystal associated
      material was heavily stained. Western blot analysis recognized 7 protein bands in
      the urine. The urinary expression of H1, H3 and pre-alpha-inhibitor was
      significantly increased. CONCLUSIONS: Apparently hyperoxaluria and renal calcium
      oxalate crystal deposition result in the increased expression of crystallization
      inhibitors, such as inter-alpha-inhibitor related proteins, in the kidneys and
      urine. Results indicate that kidneys respond to nephrolithic challenges by
      producing proteins that inhibit crystal formation and retention.

PMID- 11342957
TI  - Renal parenchymal injury after standard and mini percutaneous nephrostolithotomy.
AB  - PURPOSE: Mini percutaneous nephrostolithotomy was developed for use in children
      and in adults with a reduced renal reserve to minimize the morbidity and renal
      parenchymal damage presumed to occur with traditional percutaneous
      nephrostolithotomy. We compared the extent of renal injury incurred by different
      sized nephrostomy tracts in female farm pigs undergoing 11 or 30Fr percutaneous
      nephrostomy. MATERIALS AND METHODS: Bilateral percutaneous nephrostomy was
      attempted via a mid or lower pole calix under fluoroscopic guidance in 6 pigs. In
      2 pigs the procedure was unsuccessful on 1 side, leaving 5 successfully
      established nephrostomy tracts on each side. In each pig the right percutaneous
      tract was dilated with a 28Fr dilating balloon and a 30Fr Amplatz working sheath
      (Cook Urological, Spencer, Indiana) was positioned in the collecting system. On
      the left side an 11Fr sheath (Cook Urological) was placed. The sheaths were
      removed after 1 hour and nephrostomy tubes (22Fr on the right and 8Fr on the left
      side) were left in place overnight and then removed. Six weeks later the pigs
      were sacrificed and the kidneys were harvested. The nephrostomy tracts were
      identified grossly and examined microscopically, and the fibrotic scar was
      measured using digital analysis. The volume of scar was estimated using the
      calculated volume of a cylinder. RESULTS: At kidney harvest all 10 kidneys
      appeared grossly normal. No intra-abdominal urine collection or perirenal
      hematoma was noted. Mean estimated scar volume of the 30 and 11Fr tracts was 0.29
      and 0.40 cc, which translates into a mean fractional loss of parenchyma of 0.63%
      and 0.91%, respectively (p not significant). CONCLUSIONS: Renal parenchymal
      damage resulting from the creation of a nephrostomy tract is small compared to
      overall renal volume regardless of the size of the nephrostomy tract.
      Consequently there is no advantage to the use of a small access sheath based on
      renal scarring alone.

PMID- 11342958
TI  - Renal blood flow increase during volume expansion in hydronephrotic rats.
AB  - PURPOSE: We assessed the renal blood flow pattern in experimental hydronephrosis
      during normal hydration and extracellular volume expansion. MATERIALS AND
      METHODS: Partial obstruction of the left ureter was created in 3-week-old Sprague
      Dawley rats by embedding the ureter in a psoas muscle groove. Moderate
      hydronephrosis without kidney weight reduction developed in all cases. The
      effects on renal hemodynamics were studied with real-time ultrasound flowmetry 3
      weeks later during normal hydration and then during volume expansion. The degree
      of hydronephrosis was classified as mild, moderate or severe. RESULTS: Under
      baseline conditions renal blood flow was normal in mild and moderate
      hydronephrosis but low in severe hydronephrosis. During volume expansion renal
      blood flow increased significantly in all experimental animals (mean 14%)
      compared to that in controls, which remained unaffected or decreased (mean -3%).
      The flow increase was related to the degree of dilatation, which was 2% in mild,
      13% in moderate and 44% in severe hydronephrosis when the groups were considered
      separately. CONCLUSIONS: A significant increase in renal blood flow proportional
      to the degree of hydronephrosis occurred as a result of volume expansion. This
      finding may be explained by a state of vasodilatation combined with a reduction
      in the filtration coefficient.

PMID- 11342959
TI  - Ureteroneocystostomy contributes to late functional and morphological changes in
      rat kidney transplants.
AB  - PURPOSE: We investigated whether the surgical technique used to reconstruct the
      ureter has an impact on the late function of kidney transplants by comparing
      ureteroneocystostomy and ureteroureterostomy. To rule out alloantigeneic mediated
      effects on late graft dysfunction kidney transplants were performed in a
      syngeneic model. MATERIALS AND METHODS: Rat kidney isografts were transplanted
      with simultaneous ureteroneocystostomy or ureteroureterostomy. Unilaterally
      nephrectomized rats served as controls. Eight weeks after transplantation
      intrapelvic pressure was measured during baseline diuresis, and after
      intravesical and intrapelvic infusion. Albuminuria was determined monthly until
      sacrifice at week 52. Histomorphological analysis included the degree of
      glomerulopathy, tubular atrophy, interstitial fibrosis and intimal hyperplasia.
      CD4+- and CD8+ T cells, and macrophages were identified using immunohistochemical
      testing. RESULTS: Eight weeks after transplantation intrapelvic pressure during
      baseline diuresis and after intrapelvic infusion was significantly increased in
      rats with ureteroneocystostomy versus those with ureterostomy and unilateral
      nephrectomy, whereas intravesical infusion did not change the pressure in any
      group. During followup albuminuria after ureteroureterostomy did not differ from
      that after unilateral nephrectomy. In contrast, albuminuria significantly
      increased after ureteroneocystostomy from week 36 onward. At week 52 the ureter
      and kidney after ureteroureterostomy and unilateral nephrectomy had a normal
      appearance, whereas all ureters were dilated after ureteroneocystostomy.
      Nevertheless, 6 of the 8 kidneys in the ureteroneocystostomy group had a normal
      appearance. However, histomorphological findings in rats with transplants and
      ureterovesical anastomosis demonstrated significantly more interstitial fibrosis,
      CD8+ T cells and macrophages than isografts ureteroureterostomy. CONCLUSIONS: As
      a surgical technique for restoring the urinary tract after kidney
      transplantation, ureteroneocystostomy contributes to the development of long-term
      functional and histological renal changes. Partial obstruction may be the cause
      of this renal impairment.

PMID- 11342960
TI  - Expression and immunogenicity of oncofetal antigen-immature laminin receptor in
      human renal cell carcinoma.
AB  - PURPOSE: The 32 to 44 kDa. oncofetal antigen-immature laminin receptor (OFA-iLR)
      is a multifunctional protein expressed by various tumors, including breast, lung,
      ovary and prostate carcinoma as well as lymphoma. OFA-iLR has been implicated in
      tumor invasiveness, metastasis and growth. Interferon-gamma producing effector T
      cells and interleukin (IL)-10 producing suppressor T cells specific for OFA-iLR
      have been described. MATERIALS AND METHODS: The 43515 IgG2a anti-OFA-iLR
      monoclonal antibody was used to detect OFA-iLR expression in human renal cell
      carcinoma tissue by flow cytometry and immunoblotting. Spontaneous or therapy
      induced immune responses against OFA-iLR were determined in patients with
      metastatic renal cell carcinoma. Proliferative and cytokine (interferon-gamma and
      IL-10) responses of peripheral blood mononuclear cells from patients with renal
      cell carcinoma against recombinant OFA-iLR were assessed. RESULTS: Using flow
      cytometry OFA-iLR was detected in all 13 tumors tested. Immunoblotting revealed
      differences in OFA-iLR expression in renal cell carcinoma and normal kidney
      tissue. OFA-iLR specific proliferative and cytokine responses of mononuclear
      cells were detected in all 6 patients tested. Importantly evidence was also
      obtained that treating metastatic renal cell carcinoma with tumor lysate pulsed
      dendritic cells would enhance OFA-iLR specific immunity. CONCLUSIONS: This study
      demonstrates that OFA-iLR is an immunogenic tumor associated antigen in human
      renal cell carcinoma. OFA-iLR specific effector T cells producing interferon
      gamma may have a role in the control of tumor growth, whereas suppressor T cells
      producing IL-10 may promote tumor tolerance and, thus, tumor progression.

PMID- 11342961
TI  - Metallothionein expression in renal cell carcinoma: subcellular localization and
      prognostic significance.
AB  - PURPOSE: We investigated the immunohistochemical localization of metallothionein
      (MT) in renal cell carcinoma and determined the potential role of MT expression
      as a possible prognostic variable for tumor proliferation and progression.
      MATERIALS AND METHODS: Tumor tissue blocks from 70 patients with renal cell
      carcinoma who underwent radical or partial nephrectomy were investigated. Mean
      followup plus or minus standard error was 36 +/- 3 months. Immunohistochemical
      testing was performed by the avidin-streptavidin method using a monoclonal mouse
      antiMT antibody. MT staining intensity in samples was evaluated
      semiquantitatively. The subcellular distribution of MT was also determined.
      Staining characteristics were compared with the clinicopathological results.
      RESULTS: MT immunostaining was found in 39 of 70 tumors (55.7%) and subcellulary
      MT was localized in the cytoplasm, nucleus and cell membrane. The survival of
      patients with MT immunostaining was significantly worse than that of those with
      MT negative results (p = 0.02). A significant relationship of higher tumor grade
      and MT staining intensity was observed in grades I and III (p = 0.01), and grades
      II and III (p = 0.02) tumors. No association was found of MT expression and
      pathological stage. Sarcomatoid tumors showed significantly higher MT expression
      than clear cell, papillary, granular or chromophobe tumors (p = 0.02, 0.001, 0.01
      and 0.01, respectively). MT expression was not an independent prognostic
      variable. CONCLUSIONS: MT over expression seems to be associated with malignant
      behavior and poor prognosis in renal cell carcinoma. Therefore, MT expression may
      be considered a useful marker of less differentiated and more aggressive renal
      cell carcinoma.

PMID- 11342962
TI  - Tranilast ameliorates renal tubular damage in unilateral ureteral obstruction.
AB  - PURPOSE: We determined whether tranilast, the anti-allergic agent N-(3, 4
      dimethoxyciannamoyl)-anthranilic acid, would diminish renal transforming growth
      factor-beta (TGF-beta) levels in unilateral ureteral obstruction and
      concomitantly affect renal tubular apoptosis and proliferation in that condition.
      MATERIALS AND METHODS: Tranilast (150 mg./kg.) was administered to rats 1 day
      before unilateral ureteral obstruction and each day thereafter. Kidneys were
      harvested day 14 after unilateral ureteral obstruction. Tissue TGF-beta was
      measured by bioassay using mink lung epithelial cells. Renal tubular
      proliferation and apoptosis were detected by immunostaining proliferating cell
      nuclear antigen and the terminal deoxynucleotidyl transferase mediated
      deoxyuridine triphosphate nick end labeling assay, respectively. Fibrosis was
      assessed by measuring collagen deposition with trichrome stained slides. RESULTS:
      TGF-beta bioassay showed that obstructed kidneys in controls contained
      significantly higher mean TGF-beta plus or minus standard deviation than
      unobstructed kidneys in controls (73.7 +/- 13.6 versus 14.1 +/- 5.5 pg./mg.
      tissue) and tranilast significantly decreased tissue TGF-beta in obstructed
      kidneys (15.9 +/- 4.8 pg./mg. tissue). The terminal deoxynucleotidyl transferase
      mediated deoxyuridine triphosphate nick end labeling assay demonstrated that
      obstructed kidneys in controls had significantly more mean tubular apoptosis than
      the unobstructed counterparts (36.6 +/- 6.7 versus 5.8 +/- 5.5 nuclei per high
      power field) and tranilast significantly decreased mean renal tubular apoptosis
      in obstructed kidneys (16.2 +/- 1.7 nuclei per high power field). In addition,
      immunostaining proliferating cell nuclear antigen showed that obstructed kidneys
      in controls had significantly more mean renal tubular proliferation than
      unobstructed kidneys (20.7 +/- 3.4 versus 6.2 +/- 2.1 per high power field) and
      tranilast significantly increased proliferating renal tubules in obstructed and
      unobstructed kidneys (26.5 +/- 8.3 and 14.5 +/- 3.4 per high power field,
      respectively). Control obstructed kidneys exhibited significantly more fibrosis,
      which was also blunted by tranilast. CONCLUSIONS: Tranilast significantly
      decreases tissue TGF-beta, resulting in a reduction in tubular apoptosis and an
      increase in tubular proliferation. This finding suggests that tranilast is a
      promising agent for preventing renal tubular damage in unilateral ureteral
      obstruction.

PMID- 11342963
TI  - Ureteral reconstruction: small intestine submucosa for the management of
      strictures and defects of the upper third of the ureter.
AB  - PURPOSE: We evaluated the effectiveness of small intestine submucosa in ureteral
      reconstruction. MATERIALS AND METHODS: We report an experimental study in 6
      female pigs weighing between 50 and 60 pounds. The animals were anesthetized,
      midline laparotomy was performed and two-thirds of the diameter of the upper
      third of the left ureter were incised parallel to the ureteral axis, leaving
      intact only a third of the ureteral wall for a segment of 7 cm. A 5Fr double-J*;
      stent was positioned to secure patency at all times. The created gap was then
      bridged with an small intestine submucosa patch in a cylindrical format, which
      was subsequently sutured to the proximal and distal ureteral segment. The right
      ureter served as our control and simple intubated Davis ureterotomy was
      performed. RESULTS: All animals survived the whole followup of 7 weeks.
      Histologically there was evidence of epithelial regeneration along the segments
      reconstructed with small intestine submucosa, supported by a well vascularized
      collagen and smooth muscle background. There was no evidence of foreign body
      reaction to the graft material. In vivo patency was confirmed by retrograde
      pyelography in the bridged ureters 7 weeks after the initial procedure. All the
      ureters without an small intestine submucosa bridge had ureteral stenosis without
      evidence of epithelial regeneration. CONCLUSIONS: The use of small intestine
      submucosa is a novel, effective material for the scaffolding of ureteral defects
      and/or strictures of the upper ureteral segment in the pig model.

PMID- 11342964
TI  - Localization of constitutive nitric oxide synthase isoforms and the nitric oxide
      target enzyme soluble guanylyl cyclase in the human bladder.
AB  - PURPOSE: Nitric oxide is a free radical gas synthesized from L-arginine by a
      family of isoenzymes called nitric oxide synthase that has an important role in
      smooth muscle relaxation. L-arginine, the substrate for nitric oxide synthase,
      may be beneficial under pathophysiological conditions in the bladder, as in
      interstitial cystitis. We determined the localization of nitric oxide synthase
      and the target enzyme of NO, soluble guanylyl cyclase, in the human bladder.
      MATERIALS AND METHODS: Benign bladder tissues were obtained from 18 patients with
      localized superficial bladder tumors undergoing transurethral bladder resection.
      Histochemical nicotinamide adenine dinucleotide phosphate-diaphorase staining,
      nitric oxide synthase immunohistochemical testing and soluble guanylyl cyclase
      immunoreactivity studies were performed in all benign tissue specimens. RESULTS:
      A different pattern of nitric oxide synthase expression was confirmed by
      nicotinamide adenine dinucleotide phosphate-diaphorase staining and
      immunohistochemical testing for endothelial and neuronal nitric oxide synthase.
      In addition to endothelial nitric oxide synthase expression, detrusor smooth
      muscle was recognized as an important location of endothelial nitric oxide
      synthase, while the urothelium had only small endothelial nitric oxide synthase
      positive cell clusters. Neuronal nitric oxide synthase expression was only found
      in nitrinergic fibers of the submucosal surface and between muscle cells.
      Detrusor and vascular smooth muscle as well as interstitial cells, nerve fibers
      and transitional epithelium were recognized as targets of nitric oxide, as shown
      by soluble guanylyl cyclase expression. CONCLUSIONS: The distribution of
      constitutive nitric oxide synthase isoforms and soluble guanylyl cyclase provides
      evidence of nitric oxide-cyclic guanosine monophosphate mediated regulation of
      detrusor smooth muscle relaxation, neurotransmission and blood flow. Furthermore,
      the urothelium may also be a target of nitric oxide.

PMID- 11342965
TI  - A quantitative analysis of purinoceptor expression in human fetal and adult
      bladders.
AB  - PURPOSE: In adults there is evidence that adenosine triphosphate acting at P2X
      receptors functions as a co-transmitter at vesical smooth muscle. The contractile
      mechanisms of human fetal bladder have been studied to a limited extent and it
      remains undetermined whether P2X receptors contribute. We compared the expression
      of the 7 known P2X receptors in fetal and adult human bladders using a
      quantitative polymerase chain reaction (PCR) based method. MATERIALS AND METHODS:
      Real-time quantitative reverse transcriptase-PCR provides a system for the
      detection and analysis of RNA. Four complete cadaver fetal bladders were obtained
      at 16 weeks to full-term gestation and divided into a total of 12 segments. Adult
      bladder samples were obtained from 4 patients requiring bladder biopsy. Total RNA
      was extracted from each sample and 10 ng. were used for individual PCR reactions.
      An ABI 7700 machine (PE Applied Biosystems, California) determined expression
      levels of the 7 P2X genes in total RNA. RESULTS: In adult bladders P2X1 was by
      far the predominant purinergic receptor at the messenger RNA level. The remaining
      purinergic receptors were consistently present in the order P2X1 >> P2X4 > P2X7
      >> P2X5 > P2X2 >> P2X3 = P2X6 = 0. In fetal bladders the expression of P2X1
      transcripts was much lower than in adult bladders, and P2X4 and P2X7 were also
      present. The rank order of the P2X transcript level was P2X1 = P2X4 > P2X7 >>
      P2X5 >> P2X2 >> P2X3 = P2X6 = 0. With increasing gestation the P2X receptor
      transcript level (expression) shifted from the dome to the body of the bladder.
      CONCLUSIONS: P2X1 is the predominant purinoceptor subtype in adult human
      bladders, consistent with pharmacological evidence. The fetal expression of all
      P2X receptor transcripts is much lower than in adults, suggesting that purinergic
      transmission is of less importance. However, there are also several marked
      developmental changes in purinoceptor expression in the bladder, in that P2X4 is
      expressed in developing bladders at relatively high levels. There is also a
      marked developmental change in the regional distribution of purinoceptors. These
      changes are likely to reflect the changing role of purinergic transmission in the
      control of bladder motility during fetal maturation.

PMID- 11342966
TI  - The bladder angiotensin system in female rats: response to infusions of
      angiotensin I and the angiotensin converting enzyme inhibitor enalaprilat.
AB  - PURPOSE: A local renin angiotensin (ANG) system has been identified in the
      bladder. To our knowledge little is known about this system. To define further
      the physiology of this system we performed this study. MATERIALS AND METHODS: The
      circulating and bladder tissue concentrations of ANG I and ANG II were examined
      in anesthetized Sprague-Dawley female rats in estrus, diestrus or pregnancy. Each
      was given an intravenous bolus infusion of ANG I, the ANG converting enzyme
      inhibitor enalaprilat or saline. RESULTS: The mean concentrations of ANG I and
      ANG II were markedly higher in bladder tissue than in whole blood at the highest
      levels in pregnancy. The concentration of ANG I and ANG II increased
      significantly in the bladder tissue and circulation after the ANG I infusion in
      estrus and diestrus. In pregnancy only circulatory ANG I increased, while
      circulatory ANG II, tissue ANG I and ANG II remained unchanged. Enalaprilat
      infusion was associated with an increased concentration of whole blood ANG I in
      all groups and decreased plasma ANG II in estrus and diestrus but not in
      pregnancy. The bladder tissue ANG I response was unchanged in all groups. Bladder
      tissue ANG II was decreased in estrus and diestrus but unchanged in pregnancy.
      CONCLUSIONS: These data support the hypothesis that ANG converting enzyme is
      deactivated and an alternate pathway is activated in pregnancy. The data also
      demonstrate that tissue absorption of ANG peptide is diminished in pregnancy.
      Compared with responses in similarly studied male rats the circulating conversion
      of ANG I to ANG II is delayed in female rats and responses to ANG converting
      enzyme inhibition are enhanced, thus, suggesting subtle differences in the sexes
      in the renin ANG system. Enalapril appears to have more effect at the tissue
      level in nonpregnant females than in pregnant females and male rats.

PMID- 11342967
TI  - Evidence of a peripheral role of neurokinins in detrusor hyperreflexia: a further
      study of selective tachykinin antagonists in chronic spinal injured rats.
AB  - PURPOSE: Spinal cord injury above the sacral micturition center usually leads to
      detrusor hyperreflexia, increased intravesical pressure and post-void residual
      urine. Detrusor hyperreflexia is believed to be mediated by afferent C fibers
      with tachykinins as neurotransmitters. We investigated the selective peptide
      tachykinin antagonists MEN 11420 and GR 82334 of NK-2 and NK-1 receptors,
      respectively, in a chronic rat model of detrusor hyperreflexia after suprasacral
      spinal cord injury. MATERIALS AND METHODS: Adult female Sprague-Dawley rats
      weighing 200 to 250 gm. were used. The spinal cord was transected at the T10
      level. The bladder was evacuated by the Crede maneuver 3 times daily. After 6
      weeks the rats were implanted with femoral vein and bladder dome catheters 2 days
      before filling cystometry. The 5 rats in group 1 received 100 nmol./kg. of the NK
      2 antagonist MEN 11420 intravenously. The 5 rats in group 2 received 100
      nmol./kg. of the NK-1 antagonist GR 82334 intravenously. The 5 rats in group 3
      received a combination of the same dose of each antagonist. Three repetitive
      micturition cycles were recorded before injection. Three micturition cycles were
      done 20 minutes after the injection of each antagonist. Mean cystometric
      parameters were reported, including bladder capacity, micturition pressure,
      baseline pressure, post-void residual urine and micturition volume, and the
      number and amplitude of hyperreflexic contractions greater than 15 cm. water.
      RESULTS: MEN 11420 significantly reduced the frequency of hyperreflexic
      contractions and baseline bladder pressure (p <0.05). There was no statistically
      significant effect on the other cystometric parameters. GR 82334 reduced the
      amplitude of hyperreflexic contractions but not statistically significant. A
      combination of MEN 11420 and GR 82334 significantly reduced the frequency and
      amplitude of hyperreflexic contractions (p <0.05) with no significant effects on
      other cystometric parameters, although there was a tendency toward increased
      micturition volume and bladder capacity. CONCLUSIONS: These results suggest that
      at the peripheral level there is an efferent role of tachykinins in detrusor
      hyperreflexia after spinal cord injury. NK-1 and NK-2 receptor selective
      antagonists reduced the frequency and amplitude of hyperreflexic contractions as
      well as baseline bladder pressure. This finding may lead to potential new
      therapeutic modalities using selective tachykinins antagonists with other
      pharmacological agents to combat detrusor hyperreflexia.

PMID- 11342968
TI  - Bladder dysfunction after acute urinary retention in rats.
AB  - PURPOSE: We investigated bladder function in acute urinary retention and
      subsequent catheterization in rat bladders. MATERIALS AND METHODS: The penile
      urethra in rats was clamped with a small clip and cystostomy was performed to
      infuse 3 ml. of saline for inducing acute urinary retention. At 30 minutes after
      the induction of urinary retention the cystostomy was opened to empty the
      bladder. In functional studies contractile responses to carbachol were measured
      in group 1-before, group 2-at 3 ml. of urinary retention, group 3-at 3 ml. of
      urinary retention exposed for 30 minutes and group 4-30 minutes after
      catheterization. Moreover, in vivo real-time monitoring of blood flow and vesical
      pressure were measured in the bladders with a laser Doppler flowmeter and
      cystometrography, respectively. Malonaldehyde and 4-hydroxyalkenals were measured
      by colorimetric assay in these groups. RESULTS: In functional studies the mean
      maximum contractile response value plus or minus standard deviation of carbachol
      to-bladder in groups 1 to 4 was 11.8 +/- 1.3, 11.9 +/- 1.7, 9.8 +/- 0.8 and 6.9
      +/- 0.7 gm./mm.2, respectively. In real-time monitoring of blood flow and vesical
      pressure acute urinary retention significantly decreased blood flow and increased
      vesical pressure, and subsequent catheterization increased blood flow and
      decreased vesical pressure in the bladders. The concentrations of malonaldehyde
      and 4-hydroxyalkenals in the bladders in group 4 were significantly higher than
      in the other groups. CONCLUSIONS: Our data indicate that bladder dysfunction
      after catheterization is partially caused by free radicals, which have an
      important role in bladder dysfunction during acute urinary retention.

PMID- 11342969
TI  - Herpes simplex virus mediated nerve growth factor expression in bladder and
      afferent neurons: potential treatment for diabetic bladder dysfunction.
AB  - PURPOSE: Diabetic cystopathy resulting from sensory neuropathy may potentially be
      treated by direct gene therapy. It has been suggested that nerve growth factor
      (NGF) has an ameliorative effect in preventing the death in diabetes of afferent
      dorsal root ganglion neurons, which control bladder function. We investigated NGF
      gene transfer to the bladder and bladder afferent pathways for treating diabetic
      cystopathy. We used replication competent and replication defective herpes
      simplex virus type 1 (HSV-1) vectors that express a functionally active form of
      the beta-subunit of mouse NGF (beta-NGF) to examine the level and duration of
      therapeutic gene expression after administration of the vectors. MATERIALS AND
      METHODS: NGF expression during acute (3 days) and latent (21 days) infections was
      assessed by enzyme-linked immunosorbent assay (ELISA) and immunohistochemical
      testing after the injection of 1 x 106 to 1 x 108 pfu HSV-NGF expression vectors
      into the bladder wall of adult rats. RESULTS: HSV vectors with the strong human
      cytomegalovirus immediate early promoter used to drive beta-NGF gene expression
      exhibited increased NGF 3 days after infection in the bladder and L6 to S1 dorsal
      root ganglia, where bladder afferent neurons are located. ELISA analysis revealed
      that NGF in the bladder tissue and dorsal root ganglia was increased 7 to 9 and 2
      to 4-fold, respectively, over the control vector. Increased NGF expression in L6
      to S1 dorsal root ganglia neurons was also detected by immunohistochemical
      staining with antiNGF antibodies. Extended NGF expression was detected by ELISA
      21 days after injection. Replication defective vectors containing HSV-1 latency
      promoter (LAP-2) driving NGF expressed NGF in the bladder and dorsal root ganglia
      21 days after bladder injection. ELISA analysis confirmed an approximate 2 to 3
      fold increase of NGF expression in the bladder and L6 to S1 dorsal root ganglia.
      CONCLUSIONS: The NGF gene may be transferred and expressed in the bladder and
      bladder afferent pathways using HSV vectors. To our knowledge our study
      represents the first demonstration of the effectiveness of gene therapy for
      altering neurotrophic expression in visceral sensory neurons. This technique of
      gene transfer may be useful for treating certain types of neurogenic bladder
      dysfunction, such as diabetic cystopathy, in which decreased NGF transport may be
      a causative factor.

PMID- 11342970
TI  - Time dependent smooth muscle regeneration and maturation in a bladder acellular
      matrix graft: histological studies and in vivo functional evaluation.
AB  - PURPOSE: We evaluated the time dependence of smooth muscle regeneration and
      restoration of in vivo functional properties in bladder augmented with a bladder
      acellular matrix graft. MATERIALS AND METHODS: A total of 45 Sprague-Dawley rats
      underwent augmentation cystoplasty with a bladder acellular matrix graft. Two
      rats each were sacrificed at various intervals within the first 21 days and 6
      each were sacrificed at 4, 8 and 12 weeks. This second group underwent
      preoperative and postoperative assessment of bladder function, including
      cystometry, electrostimulation and stimulation with ice water, potassium and
      carbachol, as well as labeling of the bladder wall by the injection of
      fluorescent microspheres. After sacrifice slides of the bladders prepared for
      hematoxylin and eosin, trichrome, KI67, vimentin, desmin, smooth muscle specific
      alpha-actin and fluorescent microspheres were evaluated. RESULTS: Within 2 weeks
      the number of cells in the matrix as well as the proliferation index increased
      rapidly and then decreased gradually. Erythrocytes and inflammatory cells were
      found in the matrix within 2 to 4 days, followed by fibroblasts. A bladder host
      to-matrix shift was evident by the appearance of microspheres in the matrix. Cell
      marker expression indicated the early appearance of vimentin and alpha-actin
      within the first 10 days. Distinct desmin expression was observed later, when the
      first smooth muscle cells were recognized. Functional evaluation revealed
      restored bladder function at 12 weeks. CONCLUSIONS: The time dependent increase
      of muscle cell markers during smooth muscle cell regeneration in a bladder
      acellular matrix graft is concordant with the progressive restoration of bladder
      function. These results may support the bladder acellular matrix graft concept
      for clinical application.

PMID- 11342971
TI  - Genetic analysis of hMLH1 in transitional cell carcinoma of the urinary tract:
      promoter methylation or mutation.
AB  - PURPOSE: Loss of DNA mismatch repair due to diminished expression or mutation of
      hMLH1 is associated with genomic instability followed by cancer. We performed
      genetic analyses of hMLH1 to determine whether hMLH1 alterations have a role in
      urothelial tumorigenesis. MATERIALS AND METHODS: We examined genomic DNA from 118
      sporadic transitional cell carcinomas, including 83 bladder and 35 renal pelvis
      or ureter cases, for aberrant promoter methylation and mutation in the hMLH1
      gene. Immunohistochemical reactivity to hMLH1 protein and genome instability in
      these transitional cell carcinomas were also studied. RESULTS: Two of the 118
      cases (1.7%) had microsatellite instability and hMLH1 promoter methylation with
      loss of or reduced hMLH1 protein expression. A single transitional cell carcinoma
      (0.8%) without microsatellite instability had an hMLH1 missense mutation with a C
      to-T transition, resulting in the substitution Arg217 --> Cys. Immunostaining
      with antihMLH1 antibody was found in this transitional cell carcinoma.
      CONCLUSIONS: To our knowledge these findings provide the first in vivo evidence
      for the type and frequency of possible involvement of promoter methylation and
      mutation of hMLH1 in sporadic urothelial transitional cell carcinoma. They also
      suggest that hMLH1 alterations may not account for many cases of sporadic
      transitional cell carcinoma tumorigenesis.

PMID- 11342972
TI  - The fate of bacillus Calmette-Guerin after intravesical instillation.
AB  - PURPOSE: Long-term activation of immunocompetent cells of the bladder wall as
      well as case reports of systemic infections some months or years after
      intravesical bacillus Calmette-Guerin (BCG) therapy imply that mycobacteria may
      persist in the body. Therefore. we investigated the fate of BCG in patients after
      uncomplicated intravesical instillation therapy. MATERIAL AND METHODS: A total of
      49 patients were included in the study, from whom various numbers of specimens
      were used for mycobacterial culture and molecular biological detection
      techniques. In 23 patients who received a total of 128 instillations urine,
      sputum, venous blood and bladder biopsies were screened for BCG by acid-fast
      staining and culture at different times before and after instillation. From 16 of
      the 23 patients and from an additional 26 a total of 180 bladder biopsies
      obtained at intervals 3 to 30 months after instillation were screened for
      mycobacterial 16S ribosomal DNA by a nested polymerase chain reaction protocol.
      RESULTS: No viable BCG was found in venous blood or in 127 of 128 sputum
      specimens before and 2 hours after instillation. Two of 56 bladder biopsies were
      culture positive. In urine BCG was detected in 96.4% of the specimens after 2
      hours and in 67.9% after 24 hours after instillation. The number of positive
      specimens decreased and it was 27.1% on day 7 immediately before the next
      instillation. In 14 of 44 bladder biopsies (31.8%) mycobacterial ribosomal DNA
      was found within 1 week after the sixth instillation. A positive polymerase chain
      reaction was evident up to 24 months in between 4.2% and 37.5% of the
      investigated biopsies. After 30 months no ribosomal DNA was evident in the 6
      samples available for testing. CONCLUSIONS: Nontraumatic intravesical
      instillation of BCG is not accompanied by systemic mycobacterial spread. Local
      persistence during the instillation course is evident since viable BCG is
      commonly found in the urine. Long lasting and persistent BCG DNA in the bladder
      wall may account for long-term immuno-activation. However, the remaining BCG may
      be a possible source of late systemic infections.

PMID- 11342973
TI  - Significance of matrix metalloproteinases and tissue inhibitors of
      metalloproteinase expression in the recurrence of superficial transitional cell
      carcinoma of the bladder.
AB  - PURPOSE: We determined whether expression levels of matrix metalloproteinase
      (MMP)-2, MMP-9, membrane-type MMP-1 (MT1-MMP), tissue inhibitor of
      metalloproteinase (TIMP)-1 and TIMP-2 messenger (m) RNA in superficial
      transitional cell carcinoma of the bladder may be used as predictors of tumor
      recurrence. MATERIALS AND METHODS: Total RNA was extracted from 51 superficial
      transitional cell carcinomas of the bladder, and expression levels of MMP-2, MMP
      9, MT1-MMP, TIMP-1 and TIMP-2 messenger mRNA in these specimens were measured by
      Northern blot analysis. Results were evaluated in regard to tumor recurrence.
      RESULTS: Mean MMP-9 and TIMP-2 mRNA expression in the tumors of patients with
      recurrence were 2.5 and 3-fold higher, respectively, than in those of patients
      without recurrence despite no significant differences in MMP-2, MT1-MMP or TIMP-1
      expression. The recurrence-free survival rate of patients with elevated MMP-9 and
      TIMP-2 mRNA expression was significantly lower than that of patients with normal
      MMP-9 and TIMP-2 expression, respectively. In addition, Cox's multivariate
      analysis revealed that elevated MMP-9 and TIMP-2 were strongly associated with a
      high incidence of intravesical recurrence of superficial bladder cancer.
      CONCLUSIONS: These results indicate that MMP-9 and TIMP-2 are strongly expressed
      in the tumors of patients with recurrence compared with those without recurrence
      and elevated MMP-9 and TIMP-2 may be used as predictors of recurrence in patients
      with superficial transitional cell carcinoma.

PMID- 11342974
TI  - Radiographic imaging of the artificial urinary sphincter pressure regulating
      balloon.
AB  - PURPOSE: Radiography of the artificial urinary sphincter is done for the
      postoperative evaluation of recurrent incontinence. We investigated the ability
      of urologists and radiologists to detect changes in the radiographic appearance
      of the pressure regulating balloon at various volumes of contrast solution.
      MATERIALS AND METHODS: We obtained 20 sequential radiographs of a pressure
      regulating balloon lying atop the pelvic region of a body phantom. The volume of
      contrast solution within the balloon was decreased by 1 cc in each radiograph
      from 20 to 1 cc. Urologists and radiologists examined the radiographs for changes
      in balloon size, density and circularity. Radiographs were reviewed in side-by
      side comparison with a baseline radiograph and also independently without
      reference to baseline study. RESULTS: On side-by-side comparison changes in
      balloon size, density and circularity were first seen at 17, 13 and 8 cc of
      contrast solution, respectively. On independent review changes in size, density
      and circularity were first seen at 10, 8 and 6 cc, respectively. CONCLUSIONS: If
      there are no contraindications, contrast solution should be used to fill the
      balloon component of the artificial urinary sphincter system. Immediately after
      implantation a baseline radiograph should be obtained. Without a baseline film
      for comparison radiographic imaging of the balloon does not detect changes until
      at least 50% of its volume has been lost. Because comparison imaging is
      invaluable for detecting volume loss, a radiograph should be obtained immediately
      after initial placement of the artificial urinary sphincter.

PMID- 11342975
TI  - Corporeal structural and vascular micro architecture with X-ray micro
      computerized tomography in normal and diabetic rabbits: histopathological
      correlation.
AB  - PURPOSE: The pathophysiology of diabetes mellitus induced erectile dysfunction is
      poorly understood. In patients with diffuse venous leakage structural changes in
      the corpora cavernosa have correlated with failure of the veno-occlusive
      mechanism. Three-dimensional (D) micro computerized tomography (CT) has proved to
      be an important imaging technique for the intact kidney, heart, liver and bone.
      We examined control and diabetic rabbit penises by 3-D micro CT and quantified
      any structural changes. MATERIALS AND METHODS: Male white New Zealand rabbits
      were treated with alloxan to induce diabetes or used as normal controls. Via
      aortic access at laparotomy the penile vascular tree was vasodilated with
      papaverine and perfused with radiopaque silicone rubber. X-ray micro CT was then
      performed at 21 microm. resolution and images were analyzed in 3-D using custom
      software. RESULTS: Nine diabetic rabbits with blood glucose greater than 400
      mg./dl. and 9 control animals were used for micro CT analysis. Significant
      decreases (p <0.05) were observed in the mean sinusoidal and vascular volume
      fraction plus or minus standard error of mean of the corpus cavernosum in the
      diabetic (323.7 +/- 43.1 mm.3 and 37.9 +/- 2.0%, respectively) and control (510.1
      +/- 47.4 mm.3 and 53.1 +/- 3.80%, respectively) groups. Also, the mean left and
      right cavernous artery luminal cross-sectional area in diabetics (0.15 +/- 0.02
      and 0.16 +/- 0.01 mm.2, respectively) versus controls (0.2 +/- 0.01 and 0.2 +/-
      0.01 mm.2, respectively) was significantly decreased (p <0.05). Furthermore, the
      mean left and right total cavernous artery luminal volume in diabetics (0.4 +/-
      0.07 and 0.4 +/- 0.09 mm.3, respectively) versus controls (1.0 +/- 0.13 and 0.9
      +/- 0.11 mm.3, respectively) was significantly decreased (p <0.05). CONCLUSIONS:
      Diabetic rabbit penises showed a significant decrease in corporeal vascular
      volume as well as decreased cavernous artery diameter and luminal volume compared
      to controls. This finding correlated well with the mean decrease in trabecular
      smooth muscle in control and severely diabetic rabbits on histopathological
      studies (42.2% +/- 1.5% versus 35.8% +/- 1.5%). This combination of potential
      arterial insufficiency as well as an increase in diffuse connective tissue may
      contribute to the overall pathophysiology of diabetic erectile dysfunction. These
      results suggest that 3-D x-ray micro CT with molecular analysis may be a powerful
      tool for examining the pathophysiology of diabetic erectile dysfunction.

PMID- 11342976
TI  - Osteoporosis and mild metabolic acidosis in the rat after orchiectomy and their
      prevention: should prophylactic therapy be administered to patients with androgen
      deprivation?
AB  - PURPOSE: To date there has been little research on the etiology and prophylaxis
      of osteopenia during androgen deprivation. This condition is gaining increasing
      attention, partially due to the considerable osteoporosis related side effects of
      hormone withdrawal symptoms in patients with prostate cancer. We characterized
      androgen deprivation and its prophylaxis. MATERIALS AND METHODS: A total of 36
      male Sprague-Dawley rats underwent laparotomy, orchiectomy or orchiectomy with
      subsequently treatment with calcium acetate and sodium citrate via the water
      supply. Postoperative observation was 19 weeks. Test parameters were weight
      development, testosterone, parathyroid hormone, vitamin D, osteocalcin, cross
      links, hydroxyproline and cyclic adenosine monophosphate as well as bone density,
      tensile strength, mineral content and histomorphometry. RESULTS: Animals
      subjected to orchiectomy had a reduction in bone mineral content and fracture
      energy with mild metabolic acidosis. The markers of bone metabolism were
      statistically unchanged, while the ratio of trabeculae-to-tissue area decreased.
      Animals treated with orchiectomy, calcium acetate and sodium citrate had
      moderately compensated metabolic alkalosis and increased bone minerals. Fracture
      energy was likewise normal and there was a tendency toward higher bone
      metabolism. CONCLUSIONS: Castration led to a reduced increase in body mass,
      considerable standard deviation from biochemical and histological criteria for
      tubular bone and, thus, an increased fracture risk. A possible cause may be
      reduced formation and unchanged bone loss combined with mild metabolic acidosis.
      Calcium and alkalization seem to be effective prophylaxis for androgen
      deprivation. Considering the large number of osteoporotic complications after
      androgen deprivation, further clinical studies are justified to show the benefits
      of prophylactic therapy.

PMID- 11342977
TI  - Expression patterns of cancer testis antigens in testicular germ cell tumors and
      adjacent testicular tissue.
AB  - PURPOSE: The human cancer-testis antigens (CTAs) are a group of tumor specific
      antigens recognized by cytotoxic T lymphocytes whose expression occurs in human
      malignancies as well as in normal testicular tissue. We studied a series of CTA
      gene transcripts in testicular germ cell tumors of various histological types to
      test the hypothesis that the expression of CTA in testicular germ cell tumors
      reflects developmental stages of tumorigenesis rather than constitutive tumor
      antigens recognized by cytotoxic T lymphocytes. MATERIALS AND METHODS: Total RNA
      was obtained from 31 primary and 3 metastatic testicular germ cell tumors, and 11
      parenchymal tissues adjacent to the testicular germ cell tumors. We performed an
      expression study of the CTA genes MAGE-A, MAGE-B, GAGE, PAGE-1, HOM-MEL-40
      (SSX2), NY-ESO-1, LAGE-1 and SCP-1 in these samples using reverse transcriptase
      polymerase chain reaction. RESULTS: The results showed that expression patterns
      of CTA genes depended on the histological differentiation of the testicular germ
      cell tumors. Overall CTA expression was more common in seminomas than in
      nonseminomatous germ cell tumors. Specifically all 13 seminomas (100%)
      demonstrated the positive expression of MAGE-B1 and MAGE-B2, while 3 of 17
      nonseminomatous germ cell tumor samples (18%) showed positive expression of these
      genes. All 5 teratomatous elements (100%) had homogenous null expression with
      regard to all CTA genes examined. In addition, we detected deficiencies in CTA
      expression in 7 of 11 parenchymal tissues adjacent to the testicular germ cell
      tumors (64%). CONCLUSIONS: These data support the idea that CTA transcripts in
      testicular germ cell tumors serve as developmental footprints of testicular germ
      cell tumors rather than as constitutive tumor antigens recognized by cytotoxic T
      lymphocytes.

PMID- 11342978
TI  - Studies of tin ethyl etiopurpurin photodynamic therapy of the canine prostate.
AB  - PURPOSE: Previous studies have demonstrated the technical feasibility of
      destroying prostate tissue using photodynamic therapy for benign and malignant
      disease. A series of canine studies was performed to evaluate the systemic uptake
      and distribution of the photosensitizer tin ethyl etiopurpurin (SnET2) in the
      prostate and surrounding tissues, and determine the optimal combination of drug
      dose, light dose and time interval between drug and light administration using
      transurethral and transperineal interstitial light delivery. MATERIALS AND
      METHODS: Adult male mongrel source dogs received intravenous bolus injections of
      0.5 or 1.0 mg./kg. SnET2 in 4 studies. In the first study the concentration of
      SnET2 in the prostate and surrounding tissue was measured at various time points
      after dosing. In the second study a tissue dose response relationship of SnET2
      PDT was studied after transperineal interstitial light application. The third and
      fourth studies evaluated the tissue effects of combined transurethral and
      transperineal interstitial light application on SnET2 sensitized prostates.
      RESULTS: Substantial amounts of SnET2 were measured in the prostate between 24
      and 168 hours after infusion. Drug and light dose dependent prostatic tissue
      necrosis and volume reduction were documented in the dose response relationship
      study. The combination of transurethral and transperineal light resulted in the
      extensive destruction of glandular epithelium with minimal damage to surrounding
      structures. Average prostate volume decreased 52%. Transperineal interstitial
      light delivery with multiple diffusers resulted in substantial glandular
      destruction of the prostate. An average volume reduction of more than 60% was
      achieved. CONCLUSIONS: SnET2-PDT is a viable minimally invasive treatment
      modality for prostate tissue destruction.

PMID- 11342979
TI  - The use of telomerase activity for the detection of prostatic cancer cells after
      prostatic massage.
AB  - PURPOSE: Prostate cancer is the most commonly diagnosed cancer in the United
      States. The diagnosis or followup of prostate cancer in men older than 50 years
      is based on digital rectal examination, measurement of the free-to-total
      prostatic specific antigen ratio and transrectal ultrasound assisted needle
      biopsy of the prostate. We developed and evaluated a noninvasive method for
      diagnosing prostate cancer based on the measurement of telomerase activity after
      prostatic massage in fresh voided urine or after urethral washing. MATERIALS AND
      METHODS: We obtained 36 specimens of cells after prostatic massage in the fresh
      voided urine of 16 patients who subsequently underwent radical prostatectomy and
      after urethral washing in 20 who underwent prostate needle biopsies.
      Ethylenediaminetetraacetic acid was immediately added to the collected urine or
      washing to a final concentration of 20 mM. After protein extraction by CHAPS
      buffer each specimen was tested for telomerase activity in a 2-step modified
      telomeric repeat amplification protocol assay. The 2 prostate cancer cell lines
      PC-3 and LNCaP with high telomerase activity were used as a positive control.
      RESULTS: Telomerase activity was detected in 14 of 24 samples with known prostate
      cancer (sensitivity 58%). In contrast, no telomerase activity was found in the 12
      cases without histological evidence of prostate tumor (specificity 100%). Eight
      of 9 poorly differentiated cancers expressed telomerase activity (89%), while
      only 6 of 15 well and moderately differentiated cancers showed telomerase
      activity (40%). CONCLUSIONS: Our data illustrate that telomerase activity may be
      detected in voided urine or washing after prostatic massage in patients with
      prostate cancer. Sensitivity was higher for poorly differentiated tumors. This
      approach is not currently available for detecting prostate cancer in clinical
      practice. However, these results are promising and further studies are ongoing.

PMID- 11342980
TI  - Clinical development of trastuzumab in breast cancer.
AB  - The HER-2/neu protein is thought to be a unique and useful target for antibody
      therapy of cancers overexpressing the HER-2/neu gene. The recombinant humanized
      anti-HER-2 monoclonal antibody, trastuzumab (Herceptin) is now available for
      clinical use in the U.S.A. It is also expected to be available in Japan in the
      near future. In this paper, the details of this novel biologic agent are reviewed
      in conjunction with a phase I study performed in Japan.

PMID- 11342981
TI  - Immunohistochemical analysis on biological markers in ductal carcinoma in situ of
      the breast.
AB  - BACKGROUND: The increasing use of mammographic screening has led to an increased
      detection of ductal carcinoma in situ (DCIS) of the breast. The detailed
      biological characteristics of DCIS and a new classification of DCIS based on
      these characteristics are needed. METHODS: Immunohistochemical studies were
      performed to assess the expression of c-erbB-2 (ErbB-2), estrogen receptor (ER),
      p53 and proliferative activity (Ki-67) in 65 patients with pure DCIS and 60 with
      invasive ductal carcinoma (IDC). We classified pure DCIS tumors using three
      classifications, the architectural, Nottingham, and Van Nuys classifications.
      RESULTS: ErbB-2, ER and p53 staining was positive in 34%, 66% and 21% of patients
      with DCIS, respectively, and 58%, 42% and 33% in patients with IDC, respectively.
      Ki-67 stained positively in 1.5% of patients with DCIS and 11.2% of patients with
      IDC. The comedo type showed a high rate of positive ErbB-2 and p53 staining. The
      cribriform and papillary types showed a high rate of positive ER staining. Under
      the Van Nuys classification, ErbB-2, p53 and Ki-67 expression were highest in the
      group with high nuclear grade and lowest in the group with non-high nuclear grade
      without necrosis. CONCLUSION: Although the biological markers of IDC tended to
      suggest aggressive behavior more so than those of DCIS, these differences were
      based on the histological sub-type, comedo or non-comedo. The Van Nuys
      classification best defined the subgroups of DCIS with a distinct expression
      pattern of biological markers, and the best candidates for breast-conserving
      surgery.

PMID- 11342982
TI  - Correlation between nuclear grade and biological prognostic variables in invasive
      breast cancer.
AB  - BACKGROUND: Grading of carcinomas is an estimation of differentiation. Nuclear
      grading is the cytological evaluation of tumor nuclei in comparison with the
      nuclei of normal mammary epithelial cells. Because nuclear grading does not
      involve an assessment of the growth pattern of the tumor, it applies not only to
      invasive ductal carcinoma but also to other subtypes of breast carcinoma.
      METHODS: A total of 215 primary breast carcinomas obtained from the Affiliated
      Kihoku Hospital of Wakayama Medical College were enrolled in our present study.
      Nuclear grade was evaluated according to the criteria of the National Surgical
      Adjuvant Study of Breast Cancer (NSAS-B) protocol. Immunohistochemistry was also
      performed to determine Bcl-2, p53, c-erbB-2, estrogen receptor (ER) and MIB-1
      expression in paraffin-embedded tissues for all cases. RESULTS: Thirty-two
      (14.9%) of the patients were graded as 1,124 (57.7%) as 2, and 59 (27.4%) as 3.
      Nuclear grade displayed a negative correlation with Bcl-2 expression (r=-0.308,
      p<0.0001), and a positive correlation with c-erbB-2 overexpression (r= 0.172,
      p=0.0117) and tumor proliferative index labeling by MIB-1 (r=0.485, p<0.0001).
      CONCLUSIONS: These results imply that nuclear grade is related to the
      characteristics of tumor biology, indicating that the morphology and biology of
      breast cancer are tightly linked. Our present results also suggest that adding
      the nuclear grade to the pathological diagnosis of invasive breast carcinoma may
      be clinically useful for predicting tumor behavior, for example aggressiveness,
      and for prognostication.

PMID- 11342983
TI  - Localization of gelatinolytic activity can be detected in breast cancer tissues
      by film in situ zymography.
AB  - BACKGROUND: Extracellular matrix-degrading proteinases secreted by malignant
      tumor cells have been thought to play an essential role in the processes of
      invasion and metastasis. However, existence and localization of gelatinase
      activity in breast cancer tissues have not been clarified. METHODS: We developed
      a novel film for highly reproducible detection and the localization of
      gelatinolytic activity. This film has a gelatin layer with a constant thickness 7
      microm, and adequate crosslinking to control the speed of degradation by
      proteases. Cryosections of several breast cancer tissues were put on this gelatin
      film and incubated for 16 hrs at 37 degrees C. After staining with ponceau 3R
      dye, the digested area was evaluated under light microscopy. RESULTS: Digestion
      of gelatin was detected in more than 90%of breast cancer specimens, although it
      varied in degree and area for each case. In most cases, the gelatinolytic
      activity was located within cancer nests, and was not detected in stromal cells
      surrounding cancer cells. The gelatinolytic activity was inhibited by 1,10
      phenanthroline, an inhibitor of matrix metalloproteinases (MMPs). CONCLUSIONS: In
      this study, the localization of net MMP activity was confirmed in breast cancer
      nest using film in situ zymography. Detailed analysis on the relationship between
      the strength or distribution of MMP activity and malignancy are anticipated in
      the future.

PMID- 11342984
TI  - Three-dimensional MR imaging of mammographically detected suspicious
      microcalcifications.
AB  - BACKGROUND: The purpose of this study was to evaluate the diagnostic value and
      clinical significance of three-dimensional MR imaging of the breast in patients
      with mammographically detected suspicious microcalcifications. METHODS: Forty
      patients with suspicious microcalcifications on mammography were evaluated with
      three-dimensional MR imaging. MR findings were grouped mainly by distribution of
      abnormal enhancement (linear, focal-clumped, segmental-clumped, segmental
      stippled and diffuse-stippled). These findings were compared with the mammography
      findings according to the criteria of the Breast Imaging Reporting and Data
      System (BI-RADS) and histopathologic data. RESULTS: Twenty patients had proven
      malignancies, most frequently ductal carcinoma in situ. For all the cases, linear
      (100%) and segmental-clumped type (100%) enhancement on MR imaging showed a
      significantly higher risk for malignancy. Diffuse stippled type (7%) and no
      enhancement (0%) on MR imaging indicated the lowest possibility of malignancy. 3D
      MR imaging showed a sensitivity of 90%, a specificity of 95% and an overall
      accuracy of 93% in this study. CONCLUSIONS: Three-dimensional MR imaging of the
      breast can more accurately diagnose ductal carcinoma in situ. Combined with
      mammography, this procedure is useful for reducing the number of false-positive
      biopsies and helpful for deciding the better management of patients with
      mammographically detected suspicious microcalcifications.

PMID- 11342985
TI  - Staging of palpable T1-2 invasive breast cancer with helical CT.
AB  - BACKGROUND: The purpose of this study was to evaluate the accuracy of contrast
      enhanced high resolution helical computed tomography (CT) for assessing
      locoregional staging of palpable T1-2 invasive breast cancer. METHODS: Helical CT
      studies of 156 lesions from 156 patients with invasive breast cancer before
      breast-conserving surgery were examined. A lesion was defined as positive if
      focal enhancement was detected by CT within 100 seconds after contrast material
      administration. After resection, tumors were histopathologically mapped and
      comparison made with the extent of contrast enhancement. RESULTS: Helical CT
      enabled detection of all 156 index tumors. CT enabled detection of 28 of 43
      multifocal lesions (65%) and five of five multicentric lesions (100%). In 24 of
      33 lesions (73%), CT revealed additional cancers not seen on mammography. The
      extent of tumor significantly correlated with CT measurements (r=0.76, p<0.0001).
      CONCLUSION: Helical CT of the breast is an accurate preoperative imaging modality
      for assessing the locoregional staging of T1-2 invasive breast cancer.

PMID- 11342986
TI  - Evaluation of bone metabolic markers in breast cancer with bone metastasis.
AB  - PURPOSE: In the present study, four bone metabolic markers were examined to
      clarify them meaning and clinical value in the detection of bone metastasis (BM)
      from breast cancer. METHODS: we examined serum carboxyterminal telopeptide of
      type I collagen (ICTP), tartrate resistant acid phosphatase (TRACP), total
      alkaline phosphatase (ALP) and urinary type I collagen cross-linked N
      telopeptides (NTx) as potential markers. These bone markers were evaluated
      simultaneously in 156 breast cancer patients; 114 patients without metastasis
      (group A), 23 patients with BM (group B) and 19 patients with metastasis at sites
      other than bone (group C). RESULTS: The mean values of ICTP and TRACP in group B
      were significantly greater than those in group A. Group B consisted of the
      patients with varying degrees of BM and variation in their treatments. The
      patients in group B were divided into BM (+) and BM (++) according to hot spots
      in bone scan. ICTP and TRACP were elevated in BM (++) patients compared to BM (+)
      patients (p<0.05). The values of ICTP and TRACP of the twelve patients without
      treatment in group B were significantly higher than those in group A. In the
      treated patients of group B, the mean values of ICTP and TRACP were lower in
      responders and cases of stable disease than those with progression. NTx and ALP
      were inferior to ICTP and TRACP for clinical evaluation of BM. CONCLUSIONS: We
      confirmed that ICTP and TRACP might be useful markers for screening and
      monitoring BM in breast cancer.

PMID- 11342987
TI  - Quantitative morphometric analysis of fine needle aspirates of breast carcinoma.
AB  - BACKGROUND: Reports of morphometric analysis using computerized digitized images
      of fine needle aspirates of breast cancer are rare. We aimed to evaluate whether
      quantitative morphometric estimations of cytological nuclear features could be
      used for preoperative prediction of the risk of recurrence as well as
      chemosensitivity. METHODS: Seventy consecutive breast cancer patients were
      treated with preoperative chemotherapy (Doxifluridine 800 mg/body/day, orally)
      for 4 weeks and subsequently they underwent surgery. Using Papanicolaou-stained
      cytological materials, computerized morphometric analyses were performed. Mean
      nuclear area (NA) was measured and the coefficient of variation of NA (NACV) was
      calculated as the quantitative parameter of nuclear atypism. NA and NACV were
      compared with prognostic factors (tumor size, histological grade, hormone
      receptor status, nodal status, and ploidy status), and with the response to the
      chemotherapy. RESULTS: NA and NACV were significantly associated with hormone
      receptor status and ploidy status (p<0.05). NACV correlated with histological
      grade (p<0.05). Neither NA nor NACV were associated with tumor size and nodal
      status. Patients with high NACV (>35%) had lower rates of disease-free survival
      (p<0.05) than those with low NACV (< or =35%). Responders to preoperative
      chemotherapy had statistically larger NA, higher NACV and higher S-phase fraction
      at the time of diagnosis compared with non-responders (p<0.001, p<0.0005, and
      p<0.05 respectively). CONCLUSIONS: Morphometric analysis of preoperative fine
      needle aspirates reflects important clinical information, such as the risk of
      recurrence, and particularly, chemosensitivity.

PMID- 11342988
TI  - An analysis of relapsed breast cancer in patients previously treated with breast
      conserving surgery.
AB  - BACKGROUND: Recent advances in breast surgery have focused on breast conserving
      surgery in combination with radiotherapy. In the present study, we examine by
      retrospective analysis 105 patients with breast cancer who received breast
      conserving surgery for factors influencing disease free survival. METHODS: The
      analysis was performed on 105 patients with breast cancer who received breast
      conserving surgery in our department, including 38 patients without radiotherapy
      and 67 patients treated with radiotherapy. The disease-free survival of the
      patients was analyzed using the Kaplan-Meier method. The relapsed patients were
      assessed by examining pathological features and gene expression by
      immunohistochemical staining. RESULTS: There was no significant difference in the
      disease free survival at 5 years between patients without radiotherapy (89.6%)
      and with radiotherapy (94.5%). Relapse after breast conserving surgery was found
      in 6 patients including 4 patients without radiotherapy and 2 patients with
      radiotherapy. Local relapse and bone metastasis were found in 4 (3.8%) and 2
      patients, respectively. Among the 4 local relapses, 1 patient had received
      radiotherapy and 3 patients had not. There was no significant difference between
      the type of relapse in terms of lymph node metastasis, hormone receptor, nuclear
      grade and intraductal component, but more vessel invasion was observed in the 2
      cases with bone metastasis. The overexpression of apoptosis and angiogenesis
      genes such as p53, Bax, Bcl-XL, Bcl-2 and VEGF was not common in the relapsed
      patients, whereas the overexpression of drug resistance genes, either P-gp or
      MRP1, was found in the all patients. CONCLUSIONS: Although radiotherapy may
      reduce the incidence of local relapse and increase disease free survival after
      breast conserving surgery, the development of an effective adjuvant chemotherapy
      based on drug resistance markers, is also required.

PMID- 11342989
TI  - Results of breast-conserving therapy for ductal carcinoma in situ: the Kyoto
      University experiences.
AB  - BACKGROUND: The purpose of this study was to evaluate the results of breast
      conserving therapy (BCT), defined as the combination of breast-conserving surgery
      with axillary dissection and definitive radiation therapy for ductal carcinoma in
      situ (DCIS). METHODS: Between November 1987 and March 1998, 33 patients with DCIS
      undergoing BCT at our hospital were examined. The mean age was 48. All patients
      underwent quadrantectomy or wide excision as well as axillary dissection.
      Radiation therapy consisted of 50 Gy to the ipsilateral whole breast. Boost
      irradiation of 10 Gy was given to 15 patients with close or positive margins.
      Nearly all patients received adjuvant chemotherapy with 5-fluorouracil or its
      derivatives and adjuvant endocrine therapy with tamoxifen for 2 years. RESULTS:
      The minimum and median follow-up periods were 32 and 80 months, respectively. All
      patients but one were followed. Only one patient had a non-invasive local
      recurrence, 23 months after her operation. This patient was salvaged with simple
      mastectomy. Her prognostic index score was 8. The five-year local control rate
      was 97%. No serious acute or late complications were noted. CONCLUSION: The
      results of this retrospective study substantiate favorable data and appear to
      confirm the efficacy and reasonable local recurrence rate of BCT for the
      treatment of DCIS.

PMID- 11342990
TI  - Two cases of cholesterol granuloma of the breast.
AB  - We report two cases of cholesterol granuloma of the breast clinically diagnosed
      as malignant and describe the features. The first patient was a 74-year-old woman
      who complained of a lump in the left breast. The mammography and ultrasonography
      suggested a malignant mass. Fine needle aspiration showed multinucleated giant
      cells. We suspected breast cancer, but cholesterol granuloma was diagnosed on
      excisional biopsy. The second case was a 51-year-old woman who was found to have
      a breast tumor on a screening mammography. The mammography and ultrasonography
      suggested carcinoma, but excisional biopsy revealed cholesterol granuloma.
      Reports of cholesterol granuloma of the breast are very rare. Cholesterol
      granuloma should be considered in the differential diagnosis of breast carcinoma.

PMID- 11342991
TI  - Reconstruction of breast using a laser lithographic model: a case report.
AB  - A three-dimensional laser scanner enables the measurement of surface data from
      objects with no contact, both quickly and in three dimensions. A 40-year-old
      woman with a right breast cancer had undergone a simple mastectomy. The surface
      of the chest was then measured with the non-contact three-dimensional laser
      scanner. Using the mirror image of data obtained by the same system, a mask-like
      model of the breast was made using laser lithography technology. This model was
      used for reconstruction of the breast after mastectomy. It was effective in
      determining the position and form of the breast which was to be repaired.

PMID- 11342992
TI  - A case of leiomyoma of the breast.
AB  - Leiomyomas are common in the genitourinary and gastrointestinal tracts and less
      frequent in skin and soft tissue. It is quite uncommon for them to develop in the
      breast, especially in the breast parenchyma. Only 12 cases of leiomyoma in the
      breast parenchyma proper apart from the areola have been reported. We present a
      thirteenth case, the first to be reported in Japan. Its clinical features,
      mammographic and ultrasonographic findings, histological and immunohistochemical
      characteristics are quite consistent with previous reports.

PMID- 11342993
TI  - Prevention of venous thromboembolism. International Consensus Statement.
      Guidelines compiled in accordance with the scientific evidence.

PMID- 11342994
TI  - Interchangeability of carotid and femoral intima-media thickness in risk
      stratification.
AB  - BACKGROUND: Carotid intima-media thickness (c-IMT) is an intermediate phenotype
      not only for the local but also the global arteriosclerotic status, a concept
      which has been validated by its ability to act as a marker for future
      cardiovascular and cerebrovascular events. Whether the association between c-IMT
      and risk factors, distant atherosclerotic disease and prognosis are the sole
      prerogative of the carotid artery, or whether these findings can be extrapolated
      to other arterial sites is less well studied. In view of the concept of vascular
      heterogeneity, we measured the IMT in a muscular, lower extremity artery, the
      common femoral (f-IMT), and in elastic upper extremity artery, the common
      carotid, in apparently healthy individuals and explored the relationship with
      risk factors and the individuals 10-year cardiovascular (CV) risk, calculated
      using the Framingham systolic blood pressure equation. METHODS: A population of
      156 apparently healthy normotensive Caucasian volunteers between 18 and 65 years
      was studied (mean age 43+/-13 years; 68 men, 88 women; mean arterial blood
      pressure 126 +/- 15/70 +/- 10 mmHg). The c-IMT and f-IMT were measured using a 10
      MHz vascular linear array transducer at the far walls 1 to 2 centimetres proximal
      to the right common carotid and right common femoral artery bifurcations,
      respectively. Risk factors were assessed and the 10-year cardiovascular risk was
      calculated using the Framingham systolic blood pressure equation. RESULTS: The
      median c-IMT was 0.52 mm (interquartile range 0.45-0.62 mm) and f-INT was 0.52 mm
      (0.39-0.67). Both parameters were significantly correlated (r = 0.363; p < 0.01)
      and both were significantly correlated to the calculated 10-year CV risk (r =
      0.579; p < 0.01 and r = 0.574; p < 0.01 for the carotid and c-IMT and f-IMT,
      respectively). Median risk was low: 2.11% (0.27-5.50). Although measures of
      agreement were higher for the f-IMT versus risk (0.47) than for the c-IMT versus
      risk (0.30), the former showed a significantly wider scatter with increasing age
      and with quartiles of CV risk. The c-IMT and f-IMT do not share determinant risk
      factors to the same extent and with only 20% of mutual variance explained, cannot
      be regarded as interchangeable. CONCLUSIONS: Although the c-IMT and f-IMT are
      significantly intercorrelated and correlate to the calculated 10-year CV risk,
      they are not interchangeable. While the f-IMT is less suited as a continuous
      variable for risk stratification in a low-risk population, our data suggest its
      possible use as a dichotomised risk marker.

PMID- 11342995
TI  - Worsening lipid profile is associated with progression of carotid artery
      stenosis.
AB  - BACKGROUND: To determine if uncontrolled hypercholesterolaemia predisposes to
      progression of carotid artery stenosis. METHODS: Fasting blood samples were
      collected from 76 patients referred for carotid duplex ultrasound for
      investigation of transient ischaemic attacks or recent stroke. Patients were
      grouped depending on the severity of the stenosis found. Patients on lipid
      lowering agents were excluded. The data were analysed using one way analysis of
      variance and the c2 test as appropriate. RESULTS: There were more men in the 70
      99% group (15 vs 6, c2 = 10.6, p < 0.001, Table I). The total cholesterol was
      raised in all three groups. Patients with carotid stenosis of 70-99% had
      significantly elevated triglycerides (2.4 mmol vs 1.47 mmol and 1.37 mmol, p <
      0.003), low HDL (1.14 mmol vs 1.45 mmol and 1.18 mmol, p < 0.003) and a higher
      cholesterol/HDL ratio (5.56 vs 4.29 and 4.71, p < 0.014) compared with the other
      two groups. There was no difference in lipoprotein(a) in the three groups.
      CONCLUSIONS: Increased triglycerides and low HDL cholesterol seen in the 70-99%
      group suggest that a worsening lipid profile is associated with progression of
      carotid artery stenosis.

PMID- 11342996
TI  - Carotid plaque echogenicity and types of silent CT-brain infarcts. Is there an
      association in patients with asymptomatic carotid stenosis?
AB  - BACKGROUND: The aim of this study was to identify the differences in echogenicity
      and the degree of stenosis of asymptomatic carotid plaques associated with
      different types of ipsilateral silent CT-brain infarcts. METHODS: Some 273
      asymptomatic carotid plaques (218 patients) causing 50 to 99% stenosis were
      studied with high-resolution ultrasound. B-mode images were digitised and
      normalised by assigning certain grey values to blood and adventitia. The grey
      scale median (GSM) of the plaque in the normalised image was used to quantify
      echogenicity. Every patient had a CT-brain scan which an independent
      neuroradiologist read. The presence of 1) non-lacunar and 2) lacunar silent CT
      brain infarcts ipsilateral to the carotid plaque was noted. RESULTS: The mean GSM
      of plaques associated with non-lacunar silent CT-brain infarcts was 19.6, of
      plaques associated with lacunar infarcts was 35.5 and of those associated with no
      infarcts was 32 (p=0.008, ANOVA). The mean degree of stenosis was 79%, 72% and
      73% respectively (p = 0.1, ANOVA). Plaque echogenicity (p = 0.007) and not the
      degree of stenosis (p = 0.07) predicted the presence of non-lacunar silent CT
      brain infarcts (logistic regression). CONCLUSIONS: Carotid bifurcation plaques,
      which are associated with non-lacunar silent CT-brain infarcts, are significantly
      more hypoechoic than those associated with lacunar or no infarcts. Plaques
      associated with lacunar silent infarcts and no infarcts have the same
      echogenicity and degree of stenosis. These findings suggest an embologenic
      mechanism of non-lacunar silent CT-brain infarcts that may have prognostic
      implications in patients with asymptomatic carotid stenosis. Prospective studies
      of asymptomatic carotid stenosis should assess the significance of 1) plaque
      echogenicity and 2) the presence of different types of silent CT-brain infarcts
      and atheroembolic stroke.

PMID- 11342997
TI  - A new study demonstrates the efficacy of naftidrofuryl in the treatment of
      intermittent claudication. Findings of the Naftidrofuryl Clinical Ischemia Study
      (NCIS).
AB  - BACKGROUND: The efficacy and safety of naftidrofuryl were assessed in a double
      blind, placebo controlled, parallel group study, in patients presenting with
      intermittent claudication, according to the latest European guidelines. METHODS:
      The outpatients selected were of both sexes, aged 35 to 85, with moderately
      severe chronic, stable intermittent claudication and a pain-free (PFWD) and
      maximum walking distance (MWD) on the treadmill of between 100 and 300 metres.
      They received naftidrofuryl 200 mg tid or placebo for six months and were then
      assessed during a six-month follow-up period without treatment. The primary
      outcome measures were the pain-free walking distance and maximum walking
      distance. RESULTS: Of the 221 selected patients, 196 were randomised and 181
      entered the intention-to-treat analysis. The two groups were well matched for
      demographic variables, risk factors and history of vascular disease. After six
      months of treatment, patients who received naftidrofuryl had a 92% im-provement
      of geometric pain-free walking distance versus 17% in the placebo group (p <
      0.001) and an 83% improvement of geometric maximum walking distance versus 14% in
      the placebo group (p < 0.001). During the follow-up period without treatment, the
      walking distances of the patients in the naftidrofuryl group significantly
      decreased. The incidence of adverse events was similar in the two groups.
      CONCLUSIONS: This study demonstrated the efficacy of naftidrofuryl versus placebo
      in patients with intermittent claudication with a highly significant and
      clinically relevant difference and confirmed its good safety profile.

PMID- 11342998
TI  - Long-term results of percutaneous thrombo-embolectomy in patients with
      infrainguinal embolic occlusions.
AB  - BACKGROUND: The aim of the study was to review early and long term clinical
      results of percutaneous thrombo-embolectomy in patients with acute embolic
      occlusions of the infrainguinal arteries. METHODS: Retrospective analysis of
      consecutive cases. A total of 88 procedures in 84 patients were performed between
      1986 and 1996 in a University Hospital (46 men, 42 women; mean age 67.6 +/- 14.4
      years). Patients with a history of chronic symptomatic arterial occlusive disease
      were not included in the analysis. Indications for treatment were severe
      claudication (n = 45 procedures) and limb threatening ischaemia (n = 43
      procedures). Percutaneous thrombo-embolectomy was performed via an ipsilateral
      approach by means of an end hole aspiration catheter. Local thrombolysis or
      balloon angioplasty was used as appropriate during the intervention. Follow-up
      included clinical data, ankle pressure measurements, pulse volume recordings and
      duplex sonography or angiography if indicated. RESULTS: Technical success was
      achieved in 85 (96.6%) of the 88 procedures. Two patients (2.3%) suffered major
      and two patients (2.3%) minor complications. One patient died within 30 days
      after the procedure. Mean follow-up was 3.7 +/- 2.9 years. Twelve patients (16%)
      were lost to follow-up. Primary clinical success rate was 88.4% at one and 81.7%
      at two years and declined to 76.5% at eight years. Out of the 16 interval
      failures 10 (63%) were due to recurrent embolism to the same leg. They resulted
      in nine catheter reinterventions and one bypass graft. Six patients were treated
      conservatively. Cumulative mortality was 11.7% at one year and increased to 29.5%
      at eight years. CONCLUSIONS: From our single centre experience we conclude that
      catheter treatment of acute embolic occlusion of infrainguinal arteries is safe
      and has favourable long-term RESULTS. We therefore regard the technique as a less
      invasive alternative to surgery.

PMID- 11342999
TI  - The characteristics of screened patients with abdominal aortic aneurysm.
AB  - BACKGROUND: Screening for abdominal aortic aneurysm (AAA) has not yet been
      established in Japan. We therefore report the characteristics of a screened
      population and discuss the implications of screening using ultrasound in Japan.
      METHODS: The subjects in our screening group were composed of 4428 participants
      who were 60 years of age or older. Aneurysm was detected in 16 cases, 15 males
      and 1 female, the detection rate being 0.4% in total and 0.9% in the males. We
      compare the characteristics of screened patients (n = 16) with non-screened
      patients operated on for abdominal aortic aneurysm (n = 166). RESULTS: There were
      no significant differences in the mean age or in the female ratio between the
      screened and non-screened groups (71 vs 70 y/o, 6% vs 13%, respectively).
      Solitary iliac aneurysms were significantly (p < 0.05) more frequent in the
      screened than in the non-screened group (19% vs 3%). The size of aneurysm in the
      screened group was significantly (p < 0.05) smaller compared with the non
      screened group. Sixty-three per cent of the screened group and only 8% of the non
      screened group had an aneurysm less than 40 mm in size. Aneurysm was palpable in
      only 31% of those of the screened group. There were no significant differences
      between the groups in the frequency of arteriosclerotic risk factors such as
      hypertension, ischaemic heart disease, diabetes mellitus, peripheral vascular
      disease and smoking habits. Surgical treatment was selected in 7 out of 16
      screened patients. The remaining 9 patients with small-sized abdominal aortic
      aneurysms have been carefully followed up. CONCLUSIONS: Screening for abdominal
      aortic aneurysm using ultrasound is advisable especially for male participants
      and for the detection of iliac aneurysms. This screening procedure is useful for
      early detection because the screened aneurysm is generally small-sized and
      impalpable.

PMID- 11343000
TI  - Antiplatelet and anticoagulant therapy to prevent bypass graft thrombosis in
      patients with lower extremity arterial occlusive disease.
AB  - The incidence of graft failure for above knee femoropopliteal grafts is described
      by the European Consensus Document on Critical Limb Ischaemia. It occurs in
      approximately 15% of patients when vein is used for the grafting procedure and in
      20% of patients when PTFA (polytetrafluoroethylene) or other prosthetic material
      is used. Femorodistal grafts have a much poorer outcome with 45% and 75% failure
      rates for vein and prosthetic grafts, respectively. Prevention of primary graft
      failure and thus the need for surgical reintervention is of major clinical and
      economic importance. Early failure, occurring within one month of operation, is
      usually due to technical error such as poor patient selection or operative
      technique. Approximately 10% of graft failures will fall into this time period.
      When grafts thrombose after two years, progression of native atherosclerosis
      either proximally or distally is the usual cause. This accounts for 2-3% of all
      graft failures each year. The most common time for grafts to fail is between one
      month and two years (80% of all failures) and this is the same period in which
      graft stenoses are now known to develop. There are few evidence-based
      recommendations for the use of pharmacological agents in maintaining graft
      patency following peripheral vascular surgery. This article reviews the evidence
      for or against the use of anticoagulant and antiplatelet therapy for the
      prevention of bypass graft thrombosis in patients with peripheral arterial
      occlusive disease.

PMID- 11343001
TI  - Letter of the president, International Union of Angiology.

PMID- 11343002
TI  - Gender differences in health perceptions and meaning in persons living with heart
      failure.
AB  - OBJECTIVE: The goal of this study was to determine whether gender differences
      exist in health perceptions, psychosocial adjustment to illness, and concerns
      related to illness in patients with heart failure (HF). DESIGN: Thirty-two
      patients (50% women) from a single outpatient HF clinic were asked to complete
      standardized tools to assess health perceptions and psychosocial adjustment to
      illness. Open-ended questions were used to obtain data on concerns related to HF.
      RESULTS: The women had higher health perceptions than men did; they also
      demonstrated better psychosocial adjustment to illness. The qualitative data
      further suggest that women ascribed more positive meanings to their illness than
      men did. CONCLUSION: The current study underscored the importance of gender
      differences in health perceptions related to HF. Patient teaching and counseling
      can be tailored to address the gender-specific concerns of men and women
      suffering with this condition to improve patient outcomes.

PMID- 11343003
TI  - Reliability and validity of the compliance belief scales among patients with
      heart failure.
AB  - BACKGROUND: Lack of medication and dietary compliance leads to troublesome
      symptoms and hospitalization in patients with heart failure. Compliance behaviors
      are influenced by beliefs about the behavior. OBJECTIVE: The purpose of this
      study was to evaluate the reliability and validity of the Beliefs about
      Medication Compliance Scale (BMCS) and the Beliefs about Dietary Compliance Scale
      (BDCS) among patients with heart failure. THEORETICAL FRAMEWORK: This study's
      theoretical framework is the Health Belief Model. METHODS: A convenience sample
      of 234 patients with heart failure completed the BMCS and the BDCS. Patients
      completed the scales at baseline by face-to-face interviews and at 8 and 52 weeks
      after baseline by telephone interview. RESULTS: Construct validity of the scales
      was supported by confirmatory factor analysis. Both the BMCS and the BDCS had
      benefits and barriers scales with clear factor loadings. The internal consistency
      reliability estimates of the scales ranged from.63 to.88, with the BMCS having
      some estimates lower than.70. The test-retest reliability estimates ranged
      from.07 to.57. The intraclass correlation coefficient estimates were higher
      between the 8-week and 52-week scores for all scales. Possible reasons for the
      varying estimates are discussed. CONCLUSIONS: The BMCS and the BDCS have
      documented reliability and validity. Future work should be directed at evaluating
      the responsiveness of the scales to changing patient conditions and testing
      interventions to improve medication and dietary compliance through changing
      beliefs.

PMID- 11343004
TI  - Can a nurse trained in coronary care expedite emergency department management of
      patients with acute coronary syndromes?
AB  - OBJECTIVE: The goal of this study was to determine the effect of a coronary care
      trained nurse (CCTN) on transfer times of patients presenting with acute coronary
      syndromes (ACS) from the emergency department (ED) to the coronary care unit
      (CCU) for definitive cardiac treatment (DCT). DESIGN: This was a prospective
      randomized controlled study. SETTING: The study took place in the ED of a
      metropolitan public teaching hospital in South Australia. PATIENTS: The study
      sample was comprised of 893 patients who presented to the ED with a complaint of
      chest pain. INTERVENTION: An experienced senior CCTN was randomly assigned to
      work in an ED for 16 randomly selected hours per week; comparable hours over the
      same period without a CCTN in attendance were used as control data. The major
      endpoint was time to CCU transfer where DCT was completed for patients with ACS.
      RESULTS: Out of 893 patients assessed as having possible ACS, 91 (10%) were
      admitted to the CCU, 47 with a diagnosis of unstable angina pectoris (UAP) and 44
      with a diagnosis of acute myocardial infarction. Nineteen patients required
      thrombolysis and/or percutaneous coronary angioplasty. Mean times (in minutes) to
      transfer for DCT (95% CI) were 102 (70-134) and 117 (95-139) in the presence and
      absence of a CCTN, respectively, for all ACS, and 33 (10-55) and 54 (25-82),
      respectively, for acute myocardial infarction requiring thrombolysis and/or
      percutaneous coronary angioplasty. CONCLUSIONS: These pilot data show a
      nonsignificant trend suggesting that DCT is expedited by assignment of senior
      CCTNs to EDs and provides direction for further study.

PMID- 11343005
TI  - Effects of home telemonitoring and community-based monitoring on blood pressure
      control in urban African Americans: a pilot study.
AB  - BACKGROUND: African Americans have a higher prevalence and greater severity of
      hypertension than do other minorities and whites. This fact is particularly
      problematic when one realizes that the rate of control and treatment of
      hypertension in the US population is getting worse rather than better.
      Alternative strategies to promote blood pressure control need to be tested.
      OBJECTIVES: The purpose of this pilot study was to test the following hypothesis:
      Persons who participate in nurse-managed home telemonitoring (HT) plus usual care
      or who participate in nurse-managed community-based monitoring (CBM) plus usual
      care will have greater improvement in blood pressure from baseline to 3 months'
      follow-up than will persons who receive usual care only. METHODS: This study used
      a randomized controlled design; participants were randomly assigned to 1 of 3
      groups that were stratified by use or nonuse of antihypertension medication. One
      way analysis of variance (ANOVA) and analysis of covariance (ANCOVA) controlling
      for age and body weight were used to determine changes in blood pressure from
      baseline to 3 months. The sample contained 26 African Americans with a mean age
      of 59 years. RESULTS: Both the HT group and the CBM group had clinically and
      statistically significant (P <.05) drops in systolic blood pressure (SBP) and
      diastolic blood pressure (DBP) at 3 months' follow-up, with participants in the
      HT group demonstrating the greatest improvement (HT: baseline SBP 148.8 +/- 13.8,
      DBP 90.2 +/- 5.79; 3 months' follow-up SBP 124.1 +/- 13.82, DBP 75.58 +/- 11.4;
      CBM: baseline SBP 155.25 +/- 17.014, DBP 89.42 +/- 10.95; 3 months' follow-up SBP
      142.3 +/- 12.1, DBP 78.25 +/- 6.86). There was little change in SBP or DBP at 3
      months' follow-up in the usual care only group. CONCLUSION: These are important
      pilot results, which if replicated in a larger sample will significantly improve
      care for urban African Americans with hypertension.

PMID- 11343006
TI  - Effects of a 12-week cardiac rehabilitation exercise program on motivation and
      health-promoting lifestyle.
AB  - OBJECTIVE: The purpose of this study was to determine the effects of a 12-week
      cardiac rehabilitation exercise program on the motivation and lifestyle of
      persons recovering from a recent heart attack or cardiac-related procedures.
      DESIGN: The study design was a pretest and posttest quasi-experimental, nonrandom
      assignment. SETTING: The study was conducted at 4 cardiac rehabilitation centers
      in Northeast Ohio. SUBJECTS: The study included 57 participants in a cardiac
      rehabilitation exercise program (mean age = 64 years) and 57 comparisons (mean
      age = 64.6 years) who recently had a heart attack or underwent cardiac-related
      procedures. OUTCOME MEASURE: Motivation and health-promoting lifestyle were
      measured. INTERVENTION: A 12-week cardiac rehabilitation exercise program for
      small groups of participants (fewer than 12 persons) was conducted. The program
      provided arm and leg exercises 3 times a week for 30 to 60 minutes per session at
      an intensity of 60% to 90% of the maximum heart rate. RESULTS: Analysis of
      covariance was used to analyze the data. After controlling for education, income,
      and pretest scores, the exercise group scored significantly higher than the
      comparison group in most motivation-related variables. Regarding lifestyle, after
      adjusting for the control variables both groups showed positive changes during
      the 12-week period, but no significant difference was found between the 2 groups
      in overall lifestyle. CONCLUSION: The findings of the study confirmed that
      motivational variables were modifiable. Thus, when developing health promotion
      programs for initiating and maintaining a healthy lifestyle, the relative
      importance of different motivational variables should be considered.

PMID- 11343007
TI  - Barriers and facilitators to the prescription of automated external
      defibrillators for home use in patients with heart disease: a survey of
      cardiologists.
AB  - OBJECTIVE: Because the majority of cardiac arrests occur at home, the use of
      automated external defibrillators (AEDs) in the home could potentially improve
      survival of out-of-hospital cardiac arrest. Currently, physicians must prescribe
      AEDs for home use by patients. The purpose of this study was to investigate the
      barriers and facilitators to prescription of home use of AEDs. DESIGN: Telephone
      interviews were conducted with 85 cardiologists and paper and pencil surveys (via
      fax) with 59 additional cardiologists in Washington State. OUTCOME MEASURES:
      Cardiologists were asked about their current practices and their perceived
      barriers and facilitators to prescription of AEDs for home use. RESULTS: Eighty
      five percent of the sample believed that AEDs could be effective in preventing
      death, although only 7% of the cardiologists had ever prescribed an AED. Reasons
      for nonprescription included the use of implantable cardioverter defibrillators,
      perceived lack of a clear patient niche, and lack of knowledge about the device.
      The majority of respondents reported that they would be more likely to prescribe
      AEDs if they were the standard of care (71%), were covered by insurance (67%),
      and came with comprehensive training (58%). CONCLUSION: The results showed that
      cardiologists believe that home use of AEDs can be effective but that many issues
      regarding the prescription of AEDs remain.

PMID- 11343008
TI  - Do any preoperative variables affect extubation time after coronary artery bypass
      graft surgery?
AB  - OBJECTIVE: The purpose of this study was to determine whether any preoperative
      variable had a significant effect on extubation time after coronary artery bypass
      graft surgery. DESIGN: The study design was retrospective. SETTING: The study was
      conducted in a cardiac center in the United Kingdom where 1700 cardiac surgical
      operations are performed per year. SUBJECTS: The study sample was composed of 89
      patients who had coronary artery bypass graft surgery performed by the designated
      consultant cardiac surgeon in the first 6 months of 1998. OUTCOME MEASURES: The
      measures included preoperative variables (age, gender, body mass index, cardiac
      status, pulmonary status) and extubation time. RESULTS: Mean extubation time was
      found to be 4.97 hours. Left ventricular function was found to be statistically
      significant (P =.05) to extubation time. CONCLUSIONS: We found that cardiac
      status had an effect on extubation time and that this warranted further
      investigation. No other preoperative variable had a significant effect on
      extubation time, raising questions concerning the need for strict preoperative
      exclusion criteria.

PMID- 11343009
TI  - Effect of reusing suction catheters on the occurrence of pneumonia in children.
AB  - OBJECTIVE: The purpose of this study was to determine whether disposable suction
      catheters can be reused in the same patient for a 24-hour period without
      affecting the incidence of pneumonia. DESIGN: The study design was a randomized
      controlled trial. SETTING: The study was conducted in the pediatric intensive
      care unit of a tertiary pediatric center. SAMPLE: Subjects included 486 children
      with an endotracheal tube in place. OUTCOME MEASURES: The development of
      pneumonia, diagnosed with radiographic and clinical evidence, was the measure.
      Cost analysis was also undertaken. METHOD: Subjects in the study group (n = 241)
      were suctioned using the same catheter for a 24-hour period. Those in the control
      group (n = 245) had a new catheter for each episode of suctioning. RESULTS:
      Pneumonia developed in 14 members (5.71%) of the control group and in 12 members
      (4.98%) of the study group, a difference of 0.7% (95% CI, -3.3% to 4.7%). Cost
      analysis indicated a saving of Aust $4.14 per patient per day. CONCLUSION:
      Reusing suction catheters for up to 24 hours is both safe and cost-effective.

PMID- 11343010
TI  - Shocking tachycardia.

PMID- 11343011
TI  - Premolar extraction: Observations on a case report.

PMID- 11343012
TI  - Functional orthopedics.

PMID- 11343013
TI  - More observations on the case report.

PMID- 11343014
TI  - Cervical vertebrae maturity.

PMID- 11343016
TI  - Creating a professional community--online.

PMID- 11343017
TI  - Significance of the soft tissue profile on facial esthetics.
AB  - The soft tissue profile has been studied extensively in orthodontics, primarily
      from lateral cephalometric radiographs, under the assumption that the form of the
      soft tissue outline largely determines the esthetics of the whole face. The
      purpose of this study was to assess the relative contribution of the shape of the
      soft tissue profile outline on the attractiveness of the face, as seen from the
      profile view. Pretreatment color profile facial photographs of 20 female patients
      were used. The photographs were scanned, and the soft tissue outlines were
      digitized. The average outline of the 20 original photographs was then calculated
      and used as a template for modifying the photographs with computer warping
      methods. This resulted in 20 warped photographs, all with the same soft tissue
      outline. Three additional photographs were constructed with 1 face-the composite
      average of the 20 original photographs-and 3 hairstyles from 3 of the original
      pictures. The photographs were printed and presented to 10 laypersons and 10
      orthodontists for scoring. Scoring was performed on 2 occasions separated by at
      least 1 week. On the first occasion, the original photographs of 10 of the
      patients and the warped photographs of the other 10 patients were shown. At the
      next session, the remaining 10 original and 10 warped photographs were shown. The
      3 composite photographs were interspersed with the 20 pictures shown to the
      judges in each scoring session. Judges were asked to score facial attractiveness
      on a scale of 0 to 10. The judges were unaware of both the computer modification
      of the photographs and the purpose of the study. Good agreement was noted between
      the judges, although the orthodontists tended to be more influenced by the
      profile outline than did the laypersons. The 3 averaged composite photographs
      were consistently given the highest scores. The modified photographs were given
      higher scores than their original counterparts, showing that facial
      attractiveness is influenced by soft tissue outline form. However, the score
      improvement was not sufficient to reach the level of the composite images,
      especially for faces initially judged as being unattractive. This shows that
      factors other than profile outline shape may be more influential in facial
      esthetics.

PMID- 11343018
TI  - Cephalometric digitization: A determination of the minimum scanner settings
      necessary for precise landmark identification.
AB  - This study focused on the interpretation of scanned cephalometric images after
      the digitization of the original analog film, with a variety of standard scanner
      settings. The purpose was to determine the minimum allowable resolution,
      grayscale, and color settings of these digital images, without compromising the
      precision of orthodontic landmark identification. Forty-nine orthodontic
      residents and faculty at Saint Louis University identified 13 landmarks in 3
      separate trials on either an original lateral cephalogram or 1 of 6 digitized
      radiographic images. They also subjectively assessed the quality of the image.
      Ability to identify landmarks did not differ significantly among the groups
      tested. Conversely, opinions of image quality differed significantly among the
      groups. Participants found the quality of the grayscale images without color to
      be poorer than that of the original film but could detect differences only at
      resolution extremes. Prediction of ability to identify landmarks was
      substantially greater for higher resolution images. In conclusion, the scanner
      settings used in the digitization of a cephalometric film did not matter
      significantly when standard settings were used. In addition, subjective opinion
      of image quality was predictive of how precisely landmarks were identified when
      the resolution was relatively high.

PMID- 11343019
TI  - The use of palatal rugae for the assessment of anteroposterior tooth movements.
AB  - Currently, cephalometric superimpositions are the accepted means for the
      assessment of orthodontic tooth movement. The present investigation evaluated the
      use of palatal rugae as reference points for the measurement of tooth movement,
      in a manner comparable with cephalometric superimpositions. The sample consisted
      of pretreatment and posttreatment maxillary study models and lateral
      cephalometric radiographs from 33 patients who had received orthodontic treatment
      that involved the extraction of the maxillary first permanent premolars. The mean
      age at the start of treatment was 13 years 11 months, and the average time
      between records was 35 months. The anteroposterior movement of the maxillary
      first molars and central incisors was evaluated with the use of 2 cephalometric
      variables and 12 study model variables that were reduced to 6 by the combining of
      the left and right sides. No statistical differences were found between the mean
      molar movement that was measured cephalometrically and the mean molar movement
      that was relative to the medial and lateral ends of the first and second palatal
      rugae or relative to the medial end of the third palatal ruga. Also, no
      statistical differences were found between the mean incisor movement that was
      measured cephalometrically and the mean incisor movement that was relative to the
      medial and lateral end of the third palatal ruga. These findings suggest that
      ruga landmarks can be used as reliably as cephalometric superimpositions to
      assess anteroposterior molar movements.

PMID- 11343020
TI  - A clinical and histological evaluation of titanium mini-implants as anchors for
      orthodontic intrusion in the beagle dog.
AB  - The aim of this study was to determine the anchorage potential of the titanium
      mini-implant for orthodontic intrusion of the mandibular posterior teeth. Six
      mini-implants were surgically placed around the mandibular third premolars on
      each side in 3 adult male beagle dogs. On the buccal site, three mini-implants
      were placed distal to the apex of the distal root of the third premolar, at the
      interradicular septa of the third premolar, and mesial to the apex of the mesial
      root of the third premolar, as linearly as possible. The same procedure was
      performed at the lingual site on both sides of the mandibular third premolars in
      each dog. Bilateral interradicular mini-implants on both the buccal and the
      lingual sites were used as the anchorage for the intrusion of the third premolars
      (loaded implants) and the other mini-implants were used as control (unloaded)
      implants. In 6 weeks, an intrusive force (150 g) was applied between the
      interradicular implants on the buccal and the lingual sites by closed coil
      springs run across the crowns of the third premolars. After 12 to 18 weeks of
      orthodontic intrusion, the animals were killed and their mandibles were dissected
      and prepared for histologic and fluorescent observation. The results indicated
      that the mandibular third premolars intruded 4.5 mm, on average, after 12 to 18
      weeks of orthodontic force application, with mild root resorption at the
      furcation area as well as the root apex. All the mini-implants remained stable
      during orthodontic tooth movement without any mobility or displacement. The
      morphometrical findings indicated that the calcification of the peri-implant bone
      on the loaded implants was equal to or slightly greater than those of the
      controls. In addition, 6 of the 36 mini-implants were removed after tooth
      movement, and all of them were easily removed with a screwdriver. These findings
      suggest that mini-implants are effective tools for the anchorage of orthodontic
      intrusion in beagle dogs.

PMID- 11343021
TI  - Three-dimensional finite element analysis of stress in the periodontal ligament
      of the maxillary first molar with simulated bone loss.
AB  - The purpose of the study was to use the finite element method to simulate the
      effect of alveolar bone loss on orthodontically induced stress in the periodontal
      ligament of the maxillary first molar. A 3-dimensional finite element model of a
      tooth with different levels of bone height was constructed to estimate the
      reduction in force and the increase in moment to force (M/F) ratio necessary to
      obtain evenly distributed stress in the periodontal ligament of a tooth with
      horizontal bone loss. The 3-dimensional finite model comprised a maxillary first
      molar, the periodontal ligament, and alveolar bone and consisted of 3097 nodes
      and 2521 elements. An anterior force of 300 g was applied at the center of the
      buccal crown surfaces of teeth with normal bone height and with bone loss that
      ranged from 2.0 to 6.0 mm. The results showed that force magnitude required
      lowering from 80% (2-mm bone loss) and gradually to 37% (6-mm bone loss) of the
      initial load applied to the tooth without bone loss. The countertipping moment
      (gram-millimeters) to force (gram) ratio should increase from 9 (no bone loss) to
      nearly 13 (6-mm bone loss) to maintain the same range of stress in the
      periodontal ligament as was obtained without bone loss. A linear relationship was
      observed between the amount of bone loss, the desired reduction in force
      magnitude, and the increase in M/F ratio. The results of this study indicate that
      a combination of force reduction and increased M/F ratio is required to achieve
      uniform stress in the periodontal ligament of a tooth with bone loss.

PMID- 11343022
TI  - Predicting and preventing root resorption: Part I. Diagnostic factors.
AB  - The purpose of this study was to determine whether it would be possible to
      identify pretreatment factors that will allow the clinician to predict the
      incidence, location, and severity of root resorption before the commencement of
      orthodontic treatment. The records of 868 patients who were treated with full,
      fixed edgewise appliances were obtained from 6 private offices; full-mouth
      periapical radiographs were used to accurately assess apical root resorption from
      first molar to first molar in both arches. The results showed that resorption
      occurs primarily in the maxillary anterior teeth, averaging over 1.4 mm. The
      worst resorption was seen in maxillary lateral incisors and in teeth with
      abnormal root shape (pipette, pointed, or dilacerated). Adult patients
      experienced more resorption than children did in the mandibular anterior segment
      only. Asian patients were found to experience significantly less root resorption
      than white or Hispanic patients. Increased overjet, but not overbite, was
      significantly associated with greater root resorption. There was no difference in
      either the incidence or severity of root resorption between male and female
      patients.

PMID- 11343023
TI  - Predicting and preventing root resorption: Part II. Treatment factors.
AB  - The main objective of this study was to determine which treatment factors are
      most clearly identified with external apical root resorption that is detectable
      on periapical radiographs at the end of orthodontic treatment. The records of 868
      patients who completed fixed, edgewise treatment from experienced clinicians in
      private practice were examined. The horizontal and vertical displacement of the
      root apex of the maxillary central incisor was measured on cephalometric
      radiographs. Patients who underwent first premolar extraction therapy had more
      resorption than those patients who had no extractions or had only maxillary first
      premolars removed. Duration of treatment and the horizontal (but not vertical)
      displacement of the incisor apices were significantly associated with root
      resorption. No differences were found for slot size, archwire type, use of
      elastics, and types of expansion. However, there was considerable variation among
      the 6 offices that were surveyed; 1 office averaged nearly a full millimeter more
      of resorption per anterior tooth than the office with the least amount of root
      resorption. We conclude that the clinician should exercise caution with those
      patients in whom extraction therapy is planned for overjet correction that
      requires above average treatment time. Finally, each clinician should be aware
      that the root resorption seen in one practice may be different from the root
      resorption found in another practice.

PMID- 11343024
TI  - Detection of apoptosis during orthodontic tooth movement in rats.
AB  - Experimental evidence suggests that cellular changes and tissue turnover occurs
      in the periapical tissue during tooth movement. The possible role of apoptosis in
      tooth movement has never been investigated. The purpose of this study was to show
      whether apoptosis plays any role in orthodontic tooth movement. A sample of 21
      adult male Sprague-Dawley rats was divided into 4 groups. Orthodontic appliances
      were attached to the rats for various times-to group I (n = 6) for 3 days, to
      group II (n = 6) for 1 week, and to group III (n = 6) for 2 weeks. Rats in group
      IV (n = 3) had appliances but no force and served as the control group. At the
      end of the observation period, the animals were killed and tissue blocks of
      involved teeth were processed and prepared for TUNEL (terminal deoxynucleotidyl
      transferase-mediated dUTP nick end labeling) reaction. TUNEL-positive cells from
      selected areas on each slide were counted and compared by means of an analysis of
      variance. Group I demonstrated a significantly higher (P <.05) number of positive
      cells. This suggests that the maximum apoptosis occurs approximately 3 days after
      the application of the appliance.

PMID- 11343025
TI  - Changes in mandibular growth direction during and after cervical headgear
      treatment.
AB  - Cervical headgear is widely used to modify sagittal growth in growing patients.
      However, cervical headgear can affect vertical growth as well. The purpose of
      this retrospective cephalometric study was to examine mandibular growth changes
      in 30 growing Class II patients treated with cervical headgear and full edgewise
      appliances and to compare those changes with the changes occurring in 26
      untreated controls. Cephalometric data were obtained from lateral cephalometric
      radiographs representing pretreatment, posttreatment, and postretention for each
      patient and from chronologically comparable radiographs for the control subjects.
      During the 4-year treatment or observation period, the mean mandibular rotation
      was 0.25 degrees in the treatment group and -1.7 degrees in the control group.
      After an average posttreatment period of 6 years 5 months, the mandible had
      rotated -1.5 degrees in the treatment group and -0.7 degrees in the control
      group. Mean changes in the y-axis angle and the mandibular plane angle during
      retention were not different between the 2 groups. Mandibular rotation during
      retention did not show any significant inverse correlation with mandibular
      rotation during treatment. These findings suggest that mandibular rotation during
      retention reflects the inherent growth pattern of an individual that is
      reasserted after treatment, rather than rebound. There were no significant
      differences in the size of the mandible between the 2 groups during the study
      period. None of the variables reflecting pretreatment morphology of the face had
      a clinically significant bearing on mandibular rotation. Vertical changes in the
      maxillary and mandibular molars showed no significant correlation with mandibular
      rotation, which suggests that the changes in vertical dimension of the dentition
      are not a major determinant of the rotational change of the mandible.

PMID- 11343026
TI  - Effects of cervical headgear and edgewise appliances on growing patients.
AB  - Maxillary basal bone, dentoalveolar, and dental changes in Class II Division 1
      patients treated to normal occlusion by using cervical headgear and edgewise
      appliances were retrospectively evaluated. A sample of 45 treated patients was
      compared with a group of 30 untreated patients. Subjects were drawn from the
      Department of Orthodontics, Araraquara School of Dentistry, Brazil, and ranged in
      age from 7.5 to 13.5 years. The groups were matched based on age, gender, and
      malocclusion. Roughly 87% of the treated group had a mesocephalic or
      brachicephalic pattern, and 13% had a dolicocephalic pattern. Cervical headgear
      was used until a Class I dental relationship was achieved. Our results
      demonstrated that the malocclusions were probably corrected by maintaining the
      maxillary first molars in position during maxillary growth. Maxillary basal bone
      changes (excluding dentoalveolar changes) did not differ significantly between
      the treated and the untreated groups. Molar extrusion after the use of cervical
      headgear was not supported by our data, and this must be considered in the
      treatment plan of patients who present similar facial types.

PMID- 11343027
TI  - A unique treatment approach for maxillary canine-lateral incisor transposition.
AB  - Maxillary canine-lateral incisor transposition [Mx3-2] is a relatively rare
      anomaly, with both dental and facial esthetic implications. A challenging
      treatment approach for selected cases is described in detail, including the
      mechanics and sequencing used to align the completely transposed teeth to their
      normal anatomic position in the arch. The long-term esthetic outcome warrants the
      longer treatment time and greater efforts required in the successful treatment of
      this unusual abnormality.

PMID- 11343028
TI  - A relatively minor adult case becomes significantly complex: A lesson in
      humility.
AB  - A 41-year-old white woman with no particular concerns about facial esthetics was
      first seen with bilateral Class II molar relationship, a Class I right canine,
      and a Class II left canine. Overjet was 3 mm and overbite was 0.5 mm, with no
      incisor contact. A maxillary right premolar was missing for unknown reasons and
      all 4 third molars had previously been extracted. The maxillary midline was 2 mm
      to the right of the facial midline, and the mandibular midline was 3.5 mm to the
      left of the maxillary midline. There was 7 mm of crowding in the maxillary arch
      and 6 mm of crowding in the mandibular arch, with an increased curve of Spee. The
      patient had a well-positioned maxilla, a retrognathic mandible with increased
      convexity, a Class II denture base relationship, and a vertical facial pattern.
      The treatment plan consisted of extracting the maxillary left first premolar and
      the mandibular left central incisor. After 4 months of treatment, an open bite
      from second premolar to second premolar was noted. After 6 months of treatment,
      the patient expressed concern with her chin position and mentalis hyperactivity.
      It was apparent that the orthodontic treatment had resulted in molar extrusion,
      which the musculature was not able to withstand. Treatment continued and the case
      was set up for posterior maxillary impaction and mandibular advancement surgical
      procedures.

PMID- 11343029
TI  - Acquisition of 3-dimensional shapes from images.
AB  - Advances in computer vision have started to infiltrate the specialty of
      orthodontics. During the past few years, a number of new products have appeared
      that are capable of extracting the 3-dimensional (3-D) structure of an object
      just by "looking." Examples include laser scanners for creating 3-D models of the
      face, and hand-held scanners for creating virtual models of the teeth. Such
      noninvasive methods will surely evolve rapidly and be applied to a multitude of
      diagnostic and therapeutic modalities, changing the way we think and practice.
      This article introduces the basic principles behind such technology so that we
      can better appreciate its advantages, limitations and possibilities. From the
      large number of methods for acquiring 3-D shapes from images, 4 were selected and
      are described below. For more comprehensive coverage, see the book by Klette et
      al (1).

PMID- 11343030
TI  - Litigation, Legislation, and Ethics: Before, during, and after.

PMID- 11343031
TI  - AMSPDC: an overview of its history and evolving mission.

PMID- 11343032
TI  - Early menarche and adult height: reprise of the hare and the tortoise?

PMID- 11343033
TI  - Grading the graders of congestive heart failure in children.

PMID- 11343034
TI  - Gastrointestinal polyps in children: advances in molecular genetics, diagnosis,
      and management.

PMID- 11343035
TI  - Germline characterization of early-aged onset of hereditary non-polyposis
      colorectal cancer.
AB  - OBJECTIVES: Hereditary non-polyposis colorectal cancer (HNPCC) is characterized
      by the early onset of colorectal cancer (approximately 40 years). Adolescent
      colorectal cancer is unusual in HNPCC families. We speculated that some DNA
      mismatch repair germline mutations might be associated with early onset of
      disease. STUDY DESIGN: Genomic DNA was extracted from members of a kindred with
      virulent HNPCC fitting the Amsterdam Criteria for HNPCC and sequenced for 2 DNA
      mismatch repair genes, hMSH2 and hMLH1. A sigmoid adenocarcinoma from the 14-year
      old proband was analyzed for highfrequency microsatellite instability and
      immunostained for DNA mismatch repair gene expression. RESULTS: A germline
      mutation was identified at nucleotide 676 (codon 226) of the hMLH1 gene. The C to
      T transition created a nonsense mutation, truncating the hMLH1 protein. This
      mutation also alters the splice donor sequence, because nucleotide 676 is 2 base
      pairs from the 3' end of the exon 8. The proband's tumor demonstrated high
      frequency microsatellite instability and displayed loss of hMLH1 expression,
      indicating bi-allelic inactivation of hMLH1. CONCLUSIONS: A complex mutation of
      hMLH1 at codon 226 is associated with adolescent onset of colorectal cancer in an
      HNPCC family. Genetic screening of other suspected HNPCC families with unusually
      young members with cancer might reveal certain genotypes with particularly
      virulent forms of this disease.

PMID- 11343037
TI  - The New York University Pediatric Heart Failure Index: a new method of
      quantifying chronic heart failure severity in children.
AB  - OBJECTIVE: The assessment of the severity of heart failure in pediatric patients
      is handicapped by the subjectivity of diagnostic parameters. This study evaluated
      the feasibility of a new standardized heart failure index, the New York
      University Pediatric Heart Failure Index (NYU PHFI), to quantify the degree of
      heart failure in a selected pediatric population. METHODS AND RESULTS: The index
      is a weighted, linear combination of scores based on symptoms, physical signs,
      and medical regimen. Overall, healthy children (n = 12) scored very low (0 to 2)
      on this index. Mean scores of children (<2 years; mean age, 4.8 months; n = 12)
      with a left-to-right shunt lesion declined from 11.4 (SD +/- 4.1, P <.001, 2
      tailed test) before surgery to 1.8 (SD +/- 1.3) after surgical correction of
      their cardiac defects. The average inter-observer correlation coefficient was
      0.95 (P <.001), despite a wide range of scores. CONCLUSIONS: The NYU PHFI appears
      to be a reliable and convenient instrument for measuring heart failure severity
      in children. These initial results support further testing in broader diagnostic
      and age groups and over longer periods.

PMID- 11343036
TI  - Impact of timing of pubertal maturation on growth in black and white female
      adolescents: The National Heart, Lung, and Blood Institute Growth and Health
      Study.
AB  - OBJECTIVES: To evaluate the impact of early, mid-onset, and late maturation, as
      assessed by timing of menarche, on height, height velocity, weight, body mass
      index, and sum of skinfolds in a group of white and black girls. STUDY DESIGN:
      The Growth and Health Study recruited 9- and 10-year-old girls from Richmond,
      California, Cincinnati, Ohio, and Washington, DC. There were 616 white and 539
      black participants recruited at age 9 and 550 white and 674 black participants
      recruited at age 10. Participants were seen annually for 10 visits. Longitudinal
      regression models were used to test for differences in each growth measure by
      timing of menarche across all ages and to determine whether these differences
      change with age. RESULTS: Mean age at menarche among white participants was 12.7
      years, and among black participants, 12.0 years. According to race-specific 20th
      and 80th percentiles, early maturers were tallest at early ages and shortest
      after adult stature had been attained. Peak height velocity and post-menarche
      increment in stature were greatest in early maturers and least in late maturers.
      Weight was greatest in early and least in late maturers, as was body mass index.
      Sum of skinfolds was also greatest in early and least in late maturers. There was
      no impact of timing of maturation on two common measures of regional fat
      distribution. CONCLUSIONS: Girls who matured early were shorter in early
      adulthood, despite having greater peak height velocity and post-menarchal
      increment in height. Throughout puberty, early maturers had greater ponderosity
      and adiposity, although there was no association with regional distribution of
      fat.

PMID- 11343038
TI  - A randomized, double-blind, placebo-controlled trial of single-dose intravenous
      secretin as treatment for children with autism.
AB  - OBJECTIVE: To determine whether a single injection of intravenous secretin
      results in measurable improvements in socialization and/or communication skills
      in children with autism. STUDY DESIGN: Sixty subjects with autism were randomly
      selected and assigned to either treatment or placebo group. Subjects in the
      treatment group received 2.0 clinical units of secretin per kilogram of body
      weight as a single intravenous dose. Subjects in the placebo group received
      normal saline solution. Neurodevelopmental and behavioral assessments were
      performed for all subjects before injection and at 3 and 6 weeks after injection.
      RESULTS: Assessment of language skills and parents' behavioral assessments
      revealed no significant differences between the treatment and placebo groups.
      Raters' assessments of severity of autistic symptoms did not differ for the 2
      groups at 6 weeks after injection. A marginally statistically significant
      improvement in autistic behaviors was seen in the treatment group at 3 weeks
      after injection (P =.051). CONCLUSIONS: A single dose of intravenous secretin
      does not appear to have significant effects on either parents' perception of
      autistic behaviors or language skills at 6 weeks after injection. Transient,
      marginally significant improvements in autistic behaviors may occur in some
      children.

PMID- 11343039
TI  - Children's school performance is not impaired by short-term administration of
      diphenhydramine or loratadine.
AB  - OBJECTIVE: The purpose of this study was to determine whether a second-generation
      H1 antihistamine produces less sedation in children and permits greater learning
      in a school setting than a classic antihistamine. STUDY DESIGN: Sixty-three 8- to
      10-year-old children who had histories of seasonal allergic rhinitis but had no
      symptoms at the time of the study were randomly assigned to 1 of 3 treatment
      groups: placebo, diphenhydramine, or loratadine. Medications were administered on
      3 of 4 study days, twice 6 hours apart, while participants attended a laboratory
      school. Classroom testing at the end of each school day evaluated the children's
      retention of curriculum material. Potential sedative effects were additionally
      evaluated by self-report of somnolence and computerized reaction-time testing.
      RESULTS: No treatment-related differences emerged on the verbal instruction
      score, reading test score, reaction time, or somnolence scale. CONCLUSIONS:
      Learning and response time in children attending a laboratory school were not
      significantly affected by either antihistamine.

PMID- 11343040
TI  - A competing risk model of sudden infant death syndrome incidence in two US birth
      cohorts.
AB  - OBJECTIVES: To compare changing incidence and changing risk factors associated
      with sudden infant death syndrome (SIDS) in the 1989 and 1996 US birth cohorts.
      STUDY DESIGN: All available singleton births over 500 g from the 1989 linked
      birth-infant death file and the 1996 and 1997 Perinatal Mortality files were
      examined. A log-logistic survival model was used to explicitly account for
      declining competing risks among low birth weight infants. RESULTS: Controlling
      for maternal prenatal smoking and other confounders, SIDS incidence declined by
      >33% between the 2 survey years (adjusted odds ratio = 0.628 with 95% CI [0.598,
      0.660]). Self-reported declines in maternal prenatal smoking were also associated
      with significant declines in SIDS incidence. African American infants and infants
      born weighing <1000 g experienced increased relative risk compared with non
      Hispanic white infants born weighing >2500 g. Hispanic/Latino infants had
      significantly lower SIDS risk than non-Hispanic white infants in both years.
      Accounting for declining competing risks and other factors, relative SIDS risks
      among infants born between 500 and 1000 g increased over the study period.
      CONCLUSIONS: SIDS incidence sharply declined between 1989 and 1996. High
      incidence of SIDS in African Americans and increased relative SIDS risk for
      infants born weighing <1000 g require increased attention from clinicians and
      public health policy makers.

PMID- 11343041
TI  - Risk for birth defects among premature infants: a population-based study.
AB  - OBJECTIVE: To investigate the relationship between prematurity and birth defects.
      STUDY DESIGN: In a population-based cohort study, infants with birth defects were
      ascertained through the Metropolitan Atlanta Congenital Defects Program, a
      surveillance system with active methods of ascertainment. Gestational age data
      were obtained from birth certificates of liveborn, singleton infants with and
      without birth defects born in the 5-county metropolitan Atlanta area. RESULTS:
      Among 264,392 infants with known gestational ages born between 1989 and 1995,
      7738 were identified as having birth defects (2.93%). Premature infants (<37
      weeks' gestation) were more than two times as likely to have birth defects than
      term infants (37-41 weeks) (risk ratio = 2.43; 95% CI 2.30-2.56). This
      relationship was evident for several categories of birth defects. The rate of
      birth defects varied by gestational age categories, with the highest risk in the
      29- to 32-week gestational age category (risk ratio = 3.37). CONCLUSIONS: The
      risk for birth defects is increased in premature infants. Awareness of this
      relationship is important for clinicians caring for premature infants. The
      morbidity and mortality associated with a particular defect may be significantly
      altered by the presence of prematurity. Further study of this association may
      provide insight into the etiology of these relatively common problems.

PMID- 11343042
TI  - Efficacy of automated auditory brainstem response hearing screening in very
      preterm newborns.
AB  - OBJECTIVE: To investigate the efficacy of an automated auditory brainstem
      response (AABR) hearing screening method in very preterm newborns in the neonatal
      intensive care setting. STUDY DESIGN: In this prospective cohort study, 90
      consecutive preterm newborns (<32 weeks' gestational age) had AABR hearing
      screening weekly from birth until a bilateral pass result was obtained. If the
      newborn had a unilateral pass result, AABR screening was repeated in the same
      week. Data were analyzed by using the Kaplan-Meier survival function technique,
      resulting in a cumulative pass rate curve for postmenstrual age. Cox's regression
      method was used to analyze the effect of co-variables, such as sex and growth
      restriction, on pass rates. RESULTS: Median gestational age was 29.5 weeks
      (range, 25.3-31.9 weeks), and median birth weight was 1115 g (range, 600-1960 g).
      Mean age was 6.2 days (SD 4.3) at first test, 15.7 (SD 8.1) at second test, and
      21.4 (SD 8.6) at third test. Eighty percent (CI: 70.2%-89.8%) of the newborns
      passed at 30.3 weeks' postmenstrual age, 90% (CI: 83.6%-96.4%) passed at 31.2
      weeks, and 100% passed at 34 weeks' postmenstrual age. The attainment of these
      pass rates correlated to postmenstrual age was not significantly influenced by
      sex, growth restriction, or gestational age at birth. Postnatal pass rates (in
      days) were strongly influenced by gestational age. CONCLUSION: AABR pass rates of
      >80% can be obtained from 30 weeks' postmenstrual age. Therefore AABR neonatal
      hearing screening can be used before discharge from a neonatal intensive care
      unit.

PMID- 11343043
TI  - Iron supplementation of breast-fed Honduran and Swedish infants from 4 to 9
      months of age.
AB  - OBJECTIVE: The objective was to study the effects of iron supplementation on
      hemoglobin and iron status in 2 different populations. STUDY DESIGN: In a
      randomized, placebo-controlled, masked clinical trial, we assigned term Swedish
      (n = 101) and Honduran (n = 131) infants to 3 groups at 4 months of age: (1) iron
      supplements, 1 mg/kg/d, from 4 to 9 months, (2) placebo, 4 to 6 months and iron,
      6 to 9 months, and (3) placebo, 4 to 9 months. All infants were breast-fed
      exclusively to 6 months and partially to 9 months. RESULTS: From 4 to 6 months,
      the effect of iron (group 1 vs 2 + 3) was significant and similar in both
      populations for hemoglobin, ferritin, and zinc protoporphyrin. From 6 to 9
      months, the effect (group 2 vs group 3) was significant and similar at both sites
      for all iron status variables except hemoglobin, for which there was a
      significant effect only in Honduras. In Honduras, the prevalence of iron
      deficiency anemia at 9 months was 29% in the placebo group and 9% in the
      supplemented groups. In Sweden, iron supplements caused no reduction in the
      already low prevalence of iron deficiency anemia at 9 months (<3%). CONCLUSION:
      Iron supplementation from 4 to 9 months or 6 to 9 months significantly reduced
      iron deficiency anemia in Honduran breast-fed infants. The unexpected hemoglobin
      response at 4 to 6 months in both populations suggests that regulation of
      hemoglobin synthesis is immature at this age.

PMID- 11343044
TI  - Hypoallergenicity and efficacy of an amino acid-based formula in children with
      cow's milk and multiple food hypersensitivities.
AB  - OBJECTIVE: To determine the hypoallergenicity and efficacy of a pediatric amino
      acid-based formula (AAF), EleCare, for children with cow's milk allergy (CMA) and
      multiple food allergies (MFA). STUDY DESIGN: Hypoallergenicity was determined by
      performing blinded oral food challenges in 31 consecutive children with
      documented CMA. Growth, tolerance, and biochemical response were evaluated during
      a nonrandomized feeding study with each child serving as his or her own control.
      RESULTS: Thirty-one children (median age, 23.3 months; range, 6 months to 17.5
      years) were recruited; 29 had MFA, 17 had acute reactions and cow's milk-specific
      IgE antibody, and 14 had allergic eosinophilic gastroenteritis. At study entry,
      23 were receiving another AAF; 13 had not tolerated extensively hydrolyzed
      formula. Eighteen subjects with allergic eosinophilic gastroenteritis and/or MFA
      were followed up while receiving AAF for a median of 21 months (range, 7 to 40
      months), with biochemical analysis performed at 4 months. No statistically
      significant differences were observed in the change in weight or height National
      Center for Health Statistics z scores from entry; the percent of expected growth
      exceeded 90%. There was a small decline in percent eosinophils and increase in
      hemoglobin, hematocrit, and serum ferritin level (P < .05). Except for small
      increases in plasma leucine and valine levels (P < or = .006), the remaining
      biochemical markers were unchanged. CONCLUSIONS: The AAF was hypoallergenic and
      effective in maintaining normal growth for children with CMA and MFA.

PMID- 11343045
TI  - Montelukast added to budesonide in children with persistent asthma: a randomized,
      double-blind, crossover study.
AB  - OBJECTIVE: We tested the hypothesis that adding montelukast to budesonide would
      improve asthma control in children with inhaled glucocorticoid-dependent
      persistent asthma. STUDY DESIGN: In a multicenter, randomized, double-blind,
      crossover study, we compared the benefit of adding montelukast, 5 mg, or placebo
      once daily to budesonide, 200 microg, twice daily. RESULTS: After a 1-month run
      in with budesonide, 200 microg, twice daily, 279 children were randomized to
      montelukast or placebo. The mean +/- SD age was 10.4 +/- 2.2 years, the mean
      forced expiratory volume in 1 second (FEV(1)) was 77.7% +/- 10.6% predicted, and
      reversibility was 18.1% +/- 12.9%. Compared with adding placebo to budesonide,
      adding montelukast produced significant improvements in mean percent change from
      baseline FEV(1) (P =.062 [P =.010 for per-protocol analysis]), mean absolute
      change from baseline FEV(1) (P =.040), mean increase from baseline in morning (P
      =.023) and evening (P =.012) peak expiratory flows, decrease in exacerbation days
      by approximately 23% (P <.001), decreased beta2-agonist use (P =.013), and
      reduced blood eosinophil counts (P <.001). The treatments did not differ
      significantly with regard to safety. CONCLUSIONS: Montelukast, 5 mg, added to
      budesonide improved asthma control significantly, indicated by a small additive
      effect on lung function and a clinically relevant decrease in asthma exacerbation
      days.

PMID- 11343046
TI  - Clinical outcome after early Pseudomonas aeruginosa infection in cystic fibrosis.
AB  - OBJECTIVE: To determine the clinical consequences of acquiring Pseudomonas
      aeruginosa infection during early childhood in children with cystic fibrosis
      (CF). DESIGN: Prospective, observational cohort study of 56 children with CF
      identified by newborn screening during 1990-92. Each child underwent an annual
      bronchial lavage during the first 2 to 3 years of life. Clinical outcome was
      determined at 7 years of age. RESULTS: P aeruginosa infection was diagnosed in 24
      (43%) cohort subjects. Four children died before 7 years of age, all of whom had
      been infected with a multi-resistant, mucoid strain of P aeruginosa (P =.04). In
      survivors, P aeruginosa infection was associated with significantly increased
      morbidity as measured by lower National Institutes of Health scores, greater
      variability in lung function, increased time in the hospital, and higher rates of
      recombinant human deoxyribonuclease therapy (P <.01). In this young CF cohort,
      best forced expiratory volume in 1 second was an insensitive measure of increased
      morbidity. CONCLUSIONS: Acquisition of P aeruginosa was common by 7 years of age
      in this CF birth cohort and was associated with increased morbidity and
      mortality. An improved disease severity score would improve the evaluation and
      study of early CF lung disease.

PMID- 11343047
TI  - A prevalence study of hepatitis A virus infection in a migrant community: Is
      hepatitis A vaccine indicated?
AB  - BACKGROUND: The Advisory Committee on Immunization Practices recommends routine
      hepatitis A vaccination of children living in communities with high rates of
      hepatitis A. Rates among children living in migrant farm worker families are
      unknown. METHODS: Participants recruited from the 1243 migrant children aged 2 to
      18 years in Okeechobee County, Florida, were administered a questionnaire. A
      blood sample was taken for testing for antibodies to hepatitis A virus (anti
      HAV), and hepatitis A vaccine was administered. RESULTS: Of 244 (20%)
      participating children, 125 (51%) were anti-HAV-positive. Seropositivity
      increased with age from 34% (2- to 5-year-olds) to 81% (>/=14-year-olds) (P
      <.0001). In multivariate analysis, age (odds ratio [OR] = 1.2/year; 95% CI = 1.1
      to 1.3), having a Mexican-born father (OR = 12.2; 95% CI = 2.2 to 227.9), and age
      on moving to the United States (OR = 1.3/year; 95% CI = 1.0 to 1.6) were
      independently associated with anti-HAV positivity. Among US-born children aged 2
      to 5 years who had never left the United States, 33% were anti-HAV-positive.
      CONCLUSIONS: Anti-HAV prevalence among migrant children in Okeechobee County,
      including the youngest US-born children, is high, indicating ongoing transmission
      of HAV. Children in this and other US migrant communities may benefit from
      hepatitis A vaccination.

PMID- 11343048
TI  - Identification of poor responders to erythropoietin among children undergoing
      hemodialysis.
AB  - OBJECTIVES: To identify the factors determining a high recombinant human
      erythropoietin (rHuEPO) dose requirement and associated side effects in children
      undergoing hemodialysis. STUDY DESIGN: We retrospectively analyzed the clinical
      data of 23 children (aged 5-20 years) undergoing long-term hemodialysis. All
      subjects received intravenous rHuEPO to maintain hemoglobin levels > or = 10 g/dL
      and had iron supplement. Subjects were divided into 2 groups: those receiving
      high-dose rHuEPO (> or = 450 U/kg/wk) and those receiving an average dose (< 450
      U/kg/wk). We compared the specific variables between both groups by using Mann
      Whitney, Fisher exact, and linear regression tests; a P value < .05 was
      considered significant. RESULTS: Four of 23 subjects (17%) received high-dose
      rHuEPO despite iron repletion. These subjects were small and young and had
      frequent bacterial infections, high ferritin levels, and severe
      hyperparathyroidism. Two patients with human immunodeficiency virus infection
      required high-dose rHuEPO. The main adverse effect of high-dose rHuEPO was an
      increase in the heparin requirement during hemodialysis. CONCLUSIONS: Age, body
      weight, inflammatory status, and severity of hyperparathyroidism should be taken
      into account when adjusting rHuEPO dose for children undergoing hemodialysis.
      Furthermore, we suggest that high rHuEPO doses are related to an increase in the
      heparin requirement in these children.

PMID- 11343049
TI  - Glucocorticoid-remediable aldosteronism is associated with severe hypertension in
      early childhood.
AB  - OBJECTIVES: To review the childhood course of glucocorticoid-remediable
      aldosteronism (GRA) in order to provide management guidelines for hypertension in
      children. METHODS: Records for 20 children with GRA (aged 1 month to 18 years; 16
      with hypertension) were retrospectively reviewed. RESULTS: Of the 16 children
      with GRA who developed hypertension, 50% had moderate-severe hypertension (blood
      pressure [BP] >99th centile for age and sex); 32% had mild hypertension (BP >95th
      and <99th centile), and 18% had borderline normal BP (BP >90th and <95th
      centile). Eight of 16 children with hypertension who received directed
      monotherapy (glucocorticoid suppression or aldosterone receptor/sodium epithelial
      channel antagonists) maintained BP below the 90th centile. Three additional
      subjects receiving a combination of directed therapies or a combination of
      directed therapies and nifedipine were unable to achieve BP control. At GRA
      diagnosis, 5 of 8 children were normokalemic, and plasma renin activity was
      suppressed in 5 of 5 subjects. CONCLUSIONS: Clinicians should have a high index
      of suspicion for GRA, especially in children with severe hypertension and a
      positive family history of early-onset hypertension and/or premature hemorrhagic
      stroke. Directed monotherapy is often successful in controlling BP in GRA.

PMID- 11343050
TI  - Measuring pain accurately in children with cognitive impairments: refinement of a
      caregiver scale.
AB  - OBJECTIVE: To examine whether typical pain behavior, as reported by caregivers,
      could be used prospectively to predict future pain behavior and to derive a
      subset of core items from the Non-Communicating Children's Pain Checklist. STUDY
      DESIGN: Caregivers (n = 33) of children with cognitive impairments completed the
      Non-Communicating Children's Pain Checklist retrospectively and immediately after
      subsequent episodes of pain and distress in their homes. Odds ratios were
      computed for checklist items, and multiple regressions were used to predict
      numerical pain and distress ratings with items that had significant odds ratios.
      A logistic regression was used to test whether the items found to predict pain
      could correctly classify the presence or absence of pain in a new cohort of 63
      children with similar cognitive impairments. RESULTS: Seven of the checklist
      items had significant odds ratios: Cranky, Seeking Comfort, Change in Eyes, Less
      Active, Gesture to Part That Hurts, Tears, and Gasping. This subset of items
      significantly predicted numerical pain ratings by caregivers (multiple R =.70),
      but not distress ratings (multiple R =.31). In a second group of 63 children with
      cognitive impairments, this subset of items displayed 85% sensitivity and 89%
      specificity for pain. CONCLUSION: A subset of items from the Non-Communicating
      Children's Pain Checklist could predict pain in children with cognitive
      impairments. Caregivers' retrospective reports may be useful for clinicians
      making judgments about pain in these children.

PMID- 11343051
TI  - A randomized trial of treatment for multisystem Langerhans' cell histiocytosis.
AB  - OBJECTIVE: To compare 2 active agents, vinblastine and etoposide, in the
      treatment of multisystem Langerhans' cell histiocytosis (LCH) in an international
      randomized study. STUDY DESIGN: One hundred forty-three untreated patients were
      randomly assigned to receive 24 weeks of vinblastine (6 mg/m(2), given
      intravenously every week) or etoposide (150 mg/m(2)/d, given intravenously for 3
      days every 3 weeks), and a single initial dose of corticosteroids. RESULTS:
      Vinblastine and etoposide were equivalent (P > or = .2) in all respects: response
      at week 6 (57% and 49%); response at the last evaluation (58% and 69%); toxicity
      (47% and 58%); and probability of survival (76% and 83%) [corrected], of disease
      reactivation (61% and 55%), and of developing permanent consequences (39% and
      51%) including diabetes insipidus (22% and 23%). LCH reactivations were usually
      mild, as was toxicity. All children > or = 2 years old without risk organ
      involvement (liver, lungs, hematopoietic system, or spleen) survived. With such
      involvement, lack of rapid (within 6 weeks) response was identified as a new
      prognostic indicator, predicting a high (66%) mortality rate. CONCLUSIONS:
      Vinblastine and etoposide, with one dose of corticosteroids, are equally
      effective treatments for multisystem LCH, but patients who do not respond within
      6 weeks are at increased risk for treatment failure and may require different
      therapy.

PMID- 11343052
TI  - Infantile cholestatic jaundice associated with adult-onset type II citrullinemia.
AB  - Adult-onset type II citrullinemia, characterized by a liver-specific
      argininosuccinate synthetase deficiency, is caused by a deficiency of citrin that
      is encoded by the SLC25A13 gene. Three patients with infantile cholestatic
      jaundice were found to have mutations of the SLC25A13 gene. Adult-onset type II
      citrullinemia may be associated with infantile cholestatic disease.

PMID- 11343053
TI  - Possible clinical and histologic manifestations of adult-onset type II
      citrullinemia in early infancy.
AB  - We describe 2 patients with adult-onset type II citrullinemia who developed
      transient hypoproteinemia and jaundice in early infancy. Liver histology showed a
      marked fatty change and fibrosis. After the patients had lived without symptoms
      to the ages of 5 and 16 years, respectively, the diagnosis was made by genetic
      analysis.

PMID- 11343054
TI  - Hyponatremia and polyuria in children with central diabetes insipidus: challenges
      in diagnosis and management.
AB  - Five patients with well-controlled, long-standing, central diabetes insipidus had
      acute development of dehydration, hyponatremia, and inappropriate natriuresis in
      the setting of polyuria resistant to exogenous antidiuretic hormone. Hyponatremia
      and dehydration worsened with fluid restriction or use of exogenous antidiuretic
      hormone. We discuss the challenges in diagnosis and management of probable salt
      wasting in children with central diabetes insipidus.

PMID- 11343055
TI  - Mitochondrial DNA depletion, near-fatal metabolic acidosis, and liver failure in
      an HIV-infected child treated with combination antiretroviral therapy.
AB  - A child with controlled human immunodeficiency virus infection presented with
      neurologic deterioration, lactic acidosis, and organic aciduria. Muscle biopsy
      revealed abnormal mitochondrial (mt) morphology, reduced mt enzyme activities,
      and mtDNA depletion. After adjustment of antiretroviral therapy to a regimen free
      of nucleoside analogs, marked improvement was seen in clinical status and mt
      abnormalities.

PMID- 11343056
TI  - Effect of thimerosal recommendations on hospitals' neonatal hepatitis B
      vaccination policies.
AB  - We describe neonatal hepatitis B virus (HBV) vaccine policies in Colorado before
      and after thimerosal recommendations, plans for use of thimerosal-free HBV
      vaccine, and nurses' awareness of high-risk criteria for HBV vaccination. The
      results suggest that fewer neonates are receiving HBV vaccine at birth hospitals.

PMID- 11343057
TI  - Early surgical intervention in a patient with Kasabach-Merritt phenomenon.
AB  - A 3-day-old male infant with a 3-cm firm subcutaneous mass was found to have
      decreased platelets, decreased fibrin, and increased fibrin split products
      diagnostic of Kasabach-Merritt phenomenon. The vascular lesion was resected
      without complications. We suggest that early surgical intervention is an
      excellent therapeutic option for Kasabach-Merritt phenomenon.

PMID- 11343058
TI  - Incidence of familial Mediterranean fever (FMF) mutations among children of
      Mediterranean extraction with functional abdominal pain.
AB  - Of 59 Sephardic Jewish and Arab children in whom functional abdominal pain was
      diagnosed, we found that 20% were homozygote for the familial Mediterranean fever
      gene. Inclusion of genetic screening for familial Mediterranean fever may be
      advisable in the investigation of recurrent abdominal pain among children of
      Mediterranean extraction.

PMID- 11343060
TI  - The oral cavity in Crohn's disease.
AB  - We assessed the utility of expert oral examination as a part of the diagnostic
      evaluation of patients with suspected Crohn's disease. Of 45 patients with newly
      diagnosed CD, 25 had been examined by a dentist. Twelve (48%) of these had oral
      CD lesions. Mucosal tags constituted the most frequent form of oral lesion
      (8/12). Of 8 oral biopsy specimens, 6 (75%) contained non-caseating granulomas.
      Patients with oral CD had more oral symptoms, presented for diagnosis sooner, and
      were more likely to have other upper gastrointestinal inflammation than those
      without oral lesions. Oral manifestations of CD are common in children;
      therefore, expert oral examination may be useful during diagnostic evaluation of
      children with suspected inflammatory bowel disease.

PMID- 11343059
TI  - New insight into calcinosis of juvenile dermatomyositis: a study of composition
      and treatment.
AB  - Milk of calcium developed in 2 children with juvenile dermatomyositis. The fluid
      of the collection contained macrophages, interleukin-6, IL-1, and tumor necrosis
      factor. The patient who had dystrophic calcinosis had a dramatic improvement with
      the introduction of alendronate. These findings suggest that calcinosis of
      juvenile dermatomyositis may be mediated by activated macrophages and that
      alendronate can be an effective treatment for this condition.

PMID- 11343061
TI  - Medial medullary injury during adenoidectomy.
AB  - We report medullary injury during adenoidectomy in two children who received
      injections of local anesthetic agents into the operative bed. Initial
      manifestations included hemiparesis, nystagmus, and ataxia. Magnetic resonance
      imaging showed hemorrhagic, paramedian medullary lesions in both patients. The
      mechanism of injury is likely to be injection of fluid into the medulla.

PMID- 11343062
TI  - Foot problems in Turner's syndrome.
AB  - In a randomized, prospective study, data were collected on 23 girls with Turner's
      syndrome (TS) and an age- and sex-matched control group of 47 girls in order to
      document foot problems and to establish their cause. History revealed that 6
      (26%) girls with TS had problems with ingrowing toenails compared with none of
      the control subjects. Compared with the control subjects, girls with TS showed a
      significantly increased incidence of short, broad feet; hyperextension of the
      great toes at the interphalangeal joint; toe nail involution; inflammation of the
      periungual tissues; and intermittent lymphedema. These features in combination
      with excessive subtalar joint pronation predispose to an increased risk of
      ingrowing toenails. We conclude that foot care problems are common in TS because
      of a number of predisposing factors and that foot examination should be part of
      routine surveillance.

PMID- 11343063
TI  - Calcinosis cutis as a complication of parenteral calcium gluconate therapy.

PMID- 11343064
TI  - Possible mechanisms of pacifier protection against SIDS.

PMID- 11343066
TI  - Risks and benefits of steroids in preterm infants.

PMID- 11343069
TI  - The role of lung biopsy in deteriorating lung disease with unfavorable evolution.

PMID- 11343070
TI  - Blood pressure percentiles and standard deviations.

PMID- 11343071
TI  - On the conservative management of acute immune thrombocytopenia in children.

PMID- 11343073
TI  - Nature's 2001.

PMID- 11343074
TI  - Ruling on cleaner diesel leaves Republicans facing a dilemma.

PMID- 11343075
TI  - Human Proteome Index launched.

PMID- 11343076
TI  - Computer modellers seek out 'Ten Most Wanted' proteins.

PMID- 11343077
TI  - Major UK cancer research charities to consider merger.

PMID- 11343078
TI  - Study focuses on genetic fallout of the bomb.

PMID- 11343079
TI  - Parliament gives green light to stem-cell research.

PMID- 11343081
TI  - Mind the pseudogap.

PMID- 11343082
TI  - Global biodiversity plan needs to convince local policy-makers.

PMID- 11343083
TI  - Is this the first portrayal of tool use by a chimp?

PMID- 11343084
TI  - 1901 and all that.

PMID- 11343090
TI  - Genius loci.

PMID- 11343091
TI  - Time for gas planets to grow.

PMID- 11343093
TI  - Neurobiology. Background inhibition to the fore.

PMID- 11343095
TI  - Quantum engineering. Squeezing entanglement.

PMID- 11343096
TI  - Entomology. The alkaloid defence.

PMID- 11343097
TI  - Mammalian evolution. Relationships to chew over.

PMID- 11343098
TI  - Immunology. It takes more than two to tango.

PMID- 11343099
TI  - Molecular electronics. Nanowires begin to shine.

PMID- 11343100
TI  - DNA replication. SOS polymerases.

PMID- 11343101
TI  - Tarantula peptide inhibits atrial fibrillation.

PMID- 11343102
TI  - Photonic engineering. Aphrodite's iridescence.
AB  - The most intense colours displayed in nature result from either multilayer
      reflectors or linear diffraction gratings. Here we investigate the spectacular
      iridescence of a spine (notoseta) from the sea mouse Aphrodita sp. (Polychaeta:
      Aphroditidae). The spine normally appears to be deep red in colour, but when
      light is incident perpendicular to the axis of the spine, different colours are
      seen as stripes running parallel to the axis of the spine; over a range of
      smaller incident angles, the complete visible spectrum is reflected with a
      reflectivity of 100% to the human eye. The simple structure responsible for this
      effect is a remarkable example of photonic engineering by a living organism.

PMID- 11343103
TI  - Oceanography. Vertical mixing in the ocean.
AB  - The thermohaline circulation of the ocean results primarily from downwelling at
      sites in the Nordic and Labrador Seas and upwelling throughout the rest of the
      ocean. The latter is often described as being due to breaking internal waves.
      Here we reconcile the difference between theoretical and observed estimates of
      vertical mixing in the deep ocean by presenting a revised view of the
      thermohaline circulation, which allows for additional upwelling in the Southern
      Ocean and the separation of the North Atlantic Deep Water cell from the Antarctic
      Bottom Water cell. The changes also mean that much less wind and tidal energy
      needs to be dissipated in the deep ocean than was originally thought.

PMID- 11343104
TI  - Antibiotic resistance. How wild are wild mammals?
AB  - In bacteria associated with humans, antimicrobial resistance is common, both in
      clinical isolates and in the less-studied commensal flora, and it is thought that
      commensal and environmental bacteria might be a hidden reservoir of resistance.
      Gilliver et al. have reported that resistance is also prevalent in faecal
      bacteria from wild rodents living in northwest England. Here we test the faeces
      of moose, deer and vole in Finland and find an almost complete absence of
      resistance in enterobacteria. Resistance is thus not a universal property of
      enterobacterial populations, but may be a result of the human use of antibiotics.

PMID- 11343106
TI  - X-ray clusters of galaxies as tracers of structure in the Universe.
AB  - Clusters of galaxies are visible tracers of the network of matter in the
      Universe, marking the high-density regions where filaments of dark matter join
      together. When observed at X-ray wavelengths these clusters shine like cosmic
      lighthouses, as a consequence of the hot gas trapped within their gravitational
      potential wells. The X-ray emission is linked directly to the total mass of a
      cluster, and so can be used to investigate the mass distribution for a sizeable
      fraction of the Universe. The picture that has emerged from recent studies is
      remarkably consistent with the predictions for a low-density Universe dominated
      by cold dark matter.

PMID- 11343107
TI  - A scheme for efficient quantum computation with linear optics.
AB  - Quantum computers promise to increase greatly the efficiency of solving problems
      such as factoring large integers, combinatorial optimization and quantum physics
      simulation. One of the greatest challenges now is to implement the basic quantum
      computational elements in a physical system and to demonstrate that they can be
      reliably and scalably controlled. One of the earliest proposals for quantum
      computation is based on implementing a quantum bit with two optical modes
      containing one photon. The proposal is appealing because of the ease with which
      photon interference can be observed. Until now, it suffered from the requirement
      for non-linear couplings between optical modes containing few photons. Here we
      show that efficient quantum computation is possible using only beam splitters,
      phase shifters, single photon sources and photo-detectors. Our methods exploit
      feedback from photo-detectors and are robust against errors from photon loss and
      detector inefficiency. The basic elements are accessible to experimental
      investigation with current technology.

PMID- 11343108
TI  - Dual origin of tribosphenic mammals.
AB  - Marsupials, placentals and their close therian relatives possess complex
      (tribosphenic) molars that are capable of versatile occlusal functions. This
      functional complex is widely thought to be a key to the early diversification and
      evolutionary success of extant therians and their close relatives
      (tribosphenidans). Long thought to have arisen on northern continents,
      tribosphenic mammals have recently been reported from southern landmasses. The
      great age and advanced morphology of these new mammals has led to the alternative
      suggestion of a Gondwanan origin for the group. Implicit in both biogeographic
      hypotheses is the assumption that tribosphenic molars evolved only once in
      mammalian evolutionary history. Phylogenetic and morphometric analyses including
      these newly discovered taxa suggest a different interpretation: that mammals with
      tribosphenic molars are not monophyletic. Tribosphenic molars evolved
      independently in two ancient (holotherian) mammalian groups with different
      geographic distributions during the Jurassic/Early Cretaceous: an
      australosphenidan clade endemic to Gondwanan landmasses, survived by extant
      monotremes; and a boreosphenidan clade of Laurasian continents, including extant
      marsupials, placentals and their relatives.

PMID- 11343109
TI  - A massive reservoir of low-excitation molecular gas at high redshift.
AB  - Molecular hydrogen (H2) is an important component of galaxies because it fuels
      star formation and the accretion of gas onto active galactic nuclei (AGN), the
      two processes that can generate the large infrared luminosities of gas-rich
      galaxies. Observations of spectral-line emission from the tracer molecule carbon
      monoxide (CO) are used to probe the properties of this gas. But the lines that
      have been studied in the local Universe-mostly the lower rotational transitions
      of J = 1 --> 0 and J = 2 --> 1-have hitherto been unobservable in high-redshift
      galaxies. Instead, higher transitions have been used, although the densities and
      temperatures required to excite these higher transitions may not be reached by
      much of the gas. As a result, past observations may have underestimated the total
      amount of molecular gas by a substantial amount. Here we report the discovery of
      large amounts of low-excitation molecular gas around the infrared-luminous quasar
      APM08279+5255 at redshift z = 3.91, using the two lowest excitation lines of 12
      CO (J = 1 --> 0 and J = 2 --> 1). The maps confirm the presence of hot and dense
      gas near the nucleus, and reveal an extended reservoir of molecular gas with low
      excitation that is 10 to 100 times more massive than the gas traced by the higher
      excitation observations. This raises the possibility that significant amounts of
      low-excitation molecular gas may exist in the environments of high-redshift (z >
      3) galaxies.

PMID- 11343110
TI  - Substantial reservoirs of molecular hydrogen in the debris disks around young
      stars.
AB  - Circumstellar accretion disks transfer matter from molecular clouds to young
      stars and to the sites of planet formation. The disks observed around pre-main
      sequence stars have properties consistent with those expected for the pre-solar
      nebula from which our own Solar System formed 4.5 Gyr ago. But the 'debris' disks
      that encircle more than 15% of nearby main-sequence stars appear to have very
      small amounts of gas, based on observations of the tracer molecule carbon
      monoxide: these observations have yielded gas/dust ratios much less than 0.1,
      whereas the interstellar value is about 100 (ref. 9). Here we report observations
      of the lowest rotational transitions of molecular hydrogen (H2) that reveal large
      quantities of gas in the debris disks around the stars beta Pictoris, 49 Ceti and
      HD135344. The gas masses calculated from the data are several hundreds to a
      thousand times greater than those estimated from the CO observations, and yield
      gas/dust ratios of the same order as the interstellar value.

PMID- 11343111
TI  - Many-particle entanglement with Bose-Einstein condensates.
AB  - The possibility of creating and manipulating entangled states of systems of many
      particles is of significant interest for quantum information processing; such a
      capability could lead to new applications that rely on the basic principles of
      quantum mechanics. So far, up to four atoms have been entangled in a controlled
      way. A crucial requirement for the production of entangled states is that they
      can be considered pure at the single-particle level. Bose-Einstein condensates
      fulfil this requirement; hence it is natural to investigate whether they can also
      be used in some applications of quantum information. Here we propose a method to
      achieve substantial entanglement of a large number of atoms in a Bose-Einstein
      condensate. A single resonant laser pulse is applied to all the atoms in the
      condensate, which is then allowed to evolve freely; in this latter stage,
      collisional interactions produce entanglement between the atoms. The technique
      should be realizable with present technology.

PMID- 11343112
TI  - Indium phosphide nanowires as building blocks for nanoscale electronic and
      optoelectronic devices.
AB  - Nanowires and nanotubes carry charge and excitons efficiently, and are therefore
      potentially ideal building blocks for nanoscale electronics and optoelectronics.
      Carbon nanotubes have already been exploited in devices such as field-effect and
      single-electron transistors, but the practical utility of nanotube components for
      building electronic circuits is limited, as it is not yet possible to selectively
      grow semiconducting or metallic nanotubes. Here we report the assembly of
      functional nanoscale devices from indium phosphide nanowires, the electrical
      properties of which are controlled by selective doping. Gate-voltage-dependent
      transport measurements demonstrate that the nanowires can be predictably
      synthesized as either n- or p-type. These doped nanowires function as nanoscale
      field-effect transistors, and can be assembled into crossed-wire p-n junctions
      that exhibit rectifying behaviour. Significantly, the p-n junctions emit light
      strongly and are perhaps the smallest light-emitting diodes that have yet been
      made. Finally, we show that electric-field-directed assembly can be used to
      create highly integrated device arrays from nanowire building blocks.

PMID- 11343113
TI  - Computational design of direct-bandgap semiconductors that lattice-match silicon.
AB  - Crystalline silicon is an indirect-bandgap semiconductor, making it an
      inefficient emitter of light. The successful integration of silicon-based
      electronics with optical components will therefore require optically active (for
      example, direct-bandgap) materials that can be grown on silicon with high-quality
      interfaces. For well ordered materials, this effectively translates into the
      requirement that such materials lattice-match silicon: lattice mismatch generally
      causes cracks and poor interface properties once the mismatched overlayer exceeds
      a very thin critical thickness. But no direct-bandgap semiconductor has yet been
      produced that can lattice-match silicon, and previously suggested structures pose
      formidable challenges for synthesis. Much recent work has therefore focused on
      introducing compliant transition layers between the mismatched components. Here
      we propose a more direct solution to integrating silicon electronics with optical
      components. We have computationally designed two hypothetical direct-bandgap
      semiconductor alloys, the synthesis of which should be possible through the
      deposition of specific group-IV precursor molecules and which lattice-match
      silicon to 0.5-1% along lattice planes with low Miller indices. The calculated
      bandgaps (and hence the frequency of emitted light) lie in the window of minimal
      absorption in current optical fibres.

PMID- 11343114
TI  - Evidence from gabbro of the Troodos ophiolite for lateral magma transport along a
      slow-spreading mid-ocean ridge.
AB  - The lateral flow of magma and ductile deformation of the lower crust along
      oceanic spreading axes has been thought to play a significant role in suppressing
      both mid-ocean ridge segmentation and variations in crustal thickness. Direct
      investigation of such flow patterns is hampered by the kilometres of water that
      cover the oceanic crust, but such studies can be made on ophiolites (fragments of
      oceanic crust accreted to a continent). In the Oman ophiolite, small-scale radial
      patterns of flow have been mapped along what is thought to be the relict of a
      fast-spreading mid-ocean ridge. Here we present evidence for broad-scale along
      axis flow that has been frozen into the gabbro of the Troodos ophiolite in Cyprus
      (thought to be representative of a slow-spreading ridge axis). The gabbro suite
      of Troodos spans nearly 20 km of a segment of a fossil spreading axis, near a
      ridge-transform intersection. We mapped the pattern of magma flow by analysing
      the rocks' magnetic fabric at 20 sites widely distributed in the gabbro suite,
      and by examining the petrographic fabric at 9 sites. We infer an along-axis magma
      flow for much of the gabbro suite, which indicates that redistribution of melt
      occurred towards the segment edge in a large depth range of the oceanic crust.
      Our results support the magma plumbing structure that has been inferred
      indirectly from a seismic tomography experiment on the slow-spreading Mid
      Atlantic Ridge.

PMID- 11343115
TI  - The Earth's 'missing' niobium may be in the core.
AB  - As the Earth's metallic core segregated from the silicate mantle, some of the
      moderately siderophile ('iron-loving') elements such as vanadium and chromium are
      thought to have entered the metal phase, thus causing the observed depletions of
      these elements in the silicate part of the Earth. In contrast, refractory
      'lithophile' elements such as calcium, scandium and the rare-earth elements are
      known to be present in the same proportions in the silicate portion of the Earth
      as in the chondritic meteorites-thought to represent primitive planetary
      material. Hence these lithophile elements apparently did not enter the core.
      Niobium has always been considered to be lithophile and refractory yet it has
      been observed to be depleted relative to other elements of the same type in the
      crust and upper mantle. This observation has been used to infer the existence of
      hidden niobium-rich reservoirs in the Earth's deep mantle. Here we show, however,
      that niobium and vanadium partition in virtually identical fashion between liquid
      metal and liquid silicate at high pressure. Thus, if a significant fraction of
      the Earth's vanadium entered the core (as is thought), then so has a similar
      fraction of its niobium, and no hidden reservoir need be sought in the Earth's
      deep mantle.

PMID- 11343116
TI  - Symbiotic fungal endophytes control insect host-parasite interaction webs.
AB  - Symbiotic microorganisms that live intimately associated with terrestrial plants
      affect both the quantity and quality of resources, and thus the energy supply to
      consumer populations at higher levels in the food chain. Empirical evidence on
      resource limitation of food webs points to primary productivity as a major
      determinant of consumer abundance and trophic structure. Prey quality plays a
      critical role in community regulation. Plants infected by endophytic fungi are
      known to be chemically protected against herbivore consumption. However, the
      influence of this microbe-plant association on multi-trophic interactions remains
      largely unexplored. Here we present the effects of fungal endophytes on insect
      food webs that reflect limited energy transfer to consumers as a result of low
      plant quality, rather than low productivity. Herbivore-parasite webs on endophyte
      free grasses show enhanced insect abundance at alternate trophic levels, higher
      rates of parasitism, and increased dominance by a few trophic links. These
      results mirror predicted effects of increased productivity on food-web dynamics.
      Thus 'hidden' microbial symbionts can have community-wide impacts on the pattern
      and strength of resource-consumer interactions.

PMID- 11343117
TI  - Evolution of the bilaterian larval foregut.
AB  - Bilateria are subdivided into Protostomia and Deuterostomia. Indirect development
      through primary, ciliary larvae occurs in both of these branches; however, the
      closing blastopore develops into mouth and anus in Protostomia and into anus only
      in Deuterostomia. Because of this important difference in larval gut ontogeny,
      the tube-shaped guts in protostome and deuterostome primary larvae are thought to
      have evolved independently. To test this hypothesis, we have analysed the
      expression of brachyury, otx and goosecoid homologues in the polychaete
      Platynereis dumerilii, which develops by means of a trochophora larva-the
      primary, ciliary larva prototypic for Protostomia. Here we show that brachyury
      expression in the ventral portion of the developing foregut in Platynereis and
      also otx expression along ciliated bands in the mouth region of the trochophora
      larva parallels expression in primary larvae in Deuterostomia. In addition,
      goosecoid expression in the foregut of Platynereis mirrors the function in higher
      Deuterostomia. We present molecular evidence for the evolutionary conservation of
      larval foreguts and mouth regions of Protostomia and Deuterostomia. Our data
      indicate that Urbilateria, the common bilaterian ancestors, developed through a
      primary, ciliary larva that already possessed a tripartite tube-shaped gut.

PMID- 11343118
TI  - Self-motion and the perception of stationary objects.
AB  - One of the ways that we perceive shape is through seeing motion. Visual motion
      may be actively generated (for example, in locomotion), or passively observed. In
      the study of the perception of three-dimensional structure from motion, the non
      moving, passive observer in an environment of moving rigid objects has been used
      as a substitute for an active observer moving in an environment of stationary
      objects; this 'rigidity hypothesis' has played a central role in computational
      and experimental studies of structure from motion. Here we show that this is not
      an adequate substitution because active and passive observers can perceive three
      dimensional structure differently, despite experiencing the same visual stimulus:
      active observers' perception of three-dimensional structure depends on
      extraretinal information about their own movements. The visual system thus treats
      objects that are stationary (in an allocentric, earth-fixed reference frame)
      differently from objects that are merely rigid. These results show that action
      makes an important contribution to depth perception, and argue for a revision of
      the rigidity hypothesis to incorporate the special case of stationary objects.

PMID- 11343119
TI  - Adaptive regulation of neuronal excitability by a voltage-independent potassium
      conductance.
AB  - Many neurons receive a continuous, or 'tonic', synaptic input, which increases
      their membrane conductance, and so modifies the spatial and temporal integration
      of excitatory signals. In cerebellar granule cells, although the frequency of
      inhibitory synaptic currents is relatively low, the spillover of synaptically
      released GABA (gamma-aminobutyric acid) gives rise to a persistent conductance
      mediated by the GABA A receptor that also modifies the excitability of granule
      cells. Here we show that this tonic conductance is absent in granule cells that
      lack the alpha6 and delta-subunits of the GABAA receptor. The response of these
      granule cells to excitatory synaptic input remains unaltered, owing to an
      increase in a 'leak' conductance, which is present at rest, with properties
      characteristic of the two-pore-domain K+ channel TASK-1 (refs 9,10,11,12). Our
      results highlight the importance of tonic inhibition mediated by GABAA receptors,
      loss of which triggers a form of homeostatic plasticity leading to a change in
      the magnitude of a voltage-independent K + conductance that maintains normal
      neuronal behaviour.

PMID- 11343120
TI  - The lipid phosphatase SHIP2 controls insulin sensitivity.
AB  - Insulin is the primary hormone involved in glucose homeostasis, and impairment of
      insulin action and/or secretion has a critical role in the pathogenesis of
      diabetes mellitus. Type-II SH2-domain-containing inositol 5-phosphatase, or
      'SHIP2', is a member of the inositol polyphosphate 5-phosphatase family. In vitro
      studies have shown that SHIP2, in response to stimulation by numerous growth
      factors and insulin, is closely linked to signalling events mediated by both
      phosphoinositide-3-OH kinase and Ras/mitogen-activated protein kinase. Here we
      report the generation of mice lacking the SHIP2 gene. Loss of SHIP2 leads to
      increased sensitivity to insulin, which is characterized by severe neonatal
      hypoglycaemia, deregulated expression of the genes involved in gluconeogenesis,
      and perinatal death. Adult mice that are heterozygous for the SHIP2 mutation have
      increased glucose tolerance and insulin sensitivity associated with an increased
      recruitment of the GLUT4 glucose transporter and increased glycogen synthesis in
      skeletal muscles. Our results show that SHIP2 is a potent negative regulator of
      insulin signalling and insulin sensitivity in vivo.

PMID- 11343121
TI  - ICOS co-stimulatory receptor is essential for T-cell activation and function.
AB  - T-lymphocyte activation and immune function are regulated by co-stimulatory
      molecules. CD28, a receptor for B7 gene products, has a chief role in initiating
      T-cell immune responses. CTLA4, which binds B7 with a higher affinity, is induced
      after T-cell activation and is involved in downregulating T-cell responses. The
      inducible co-stimulatory molecule (ICOS), a third member of the CD28/CTLA4
      family, is expressed on activated T cells. Its ligand B7H/B7RP-1 is expressed on
      B cells and in non-immune tissues after injection of lipopolysaccharide into
      animals. To understand the role of ICOS in T-cell activation and function, we
      generated and analysed ICOS-deficient mice. Here we show that T-cell activation
      and proliferation are defective in the absence of ICOS. In addition, ICOS -/- T
      cells fail to produce interleukin-4 when differentiated in vitro or when primed
      in vivo. ICOS is required for humoral immune responses after immunization with
      several antigens. ICOS-/- mice showed greatly enhanced susceptibility to
      experimental autoimmune encephalomyelitis, indicating that ICOS has a protective
      role in inflammatory autoimmune diseases.

PMID- 11343122
TI  - ICOS is critical for CD40-mediated antibody class switching.
AB  - The inducible co-stimulatory molecule (ICOS) is a CD28 homologue implicated in
      regulating T-cell differentiation. Because co-stimulatory signals are critical
      for regulating T-cell activation, an understanding of co-stimulatory signals may
      enable the design of rational therapies for immune-mediated diseases. According
      to the two-signal model for T-cell activation, T cells require an antigen
      specific signal and a second, co-stimulatory, signal for optimal T-cell
      activation. The co-stimulatory signal promotes T-cell proliferation, lymphokine
      secretion and effector function. The B7-CD28 pathway provides essential signals
      for T-cell activation, but does not account for all co-stimulation. We have
      generated mice lacking ICOS (ICOS-/- ) to determine the essential functions of
      ICOS. Here we report that ICOS-/- mice exhibit profound deficits in
      immunoglobulin isotype class switching, accompanied by impaired germinal centre
      formation. Class switching was restored in ICOS-/- mice by CD40 stimulation,
      showing that ICOS promotes T-cell/B-cell collaboration through the CD40/CD40L
      pathway.

PMID- 11343123
TI  - ICOS is essential for effective T-helper-cell responses.
AB  - The outcome of T-cell responses after T-cell encounter with specific antigens is
      modulated by co-stimulatory signals, which are required for both lymphocyte
      activation and development of adaptive immunity. ICOS, an inducible co-stimulator
      with homology to CD28, is expressed on activated, but not resting T cells, and
      shows T-cell co-stimulatory function in vitro. ICOS binds specifically to its
      counter-receptor B7RP-1 (refs 5,6,7), but not to B7-1 or B7-2. Here we provide in
      vivo genetic evidence that ICOS delivers a co-stimulatory signal that is
      essential both for efficient interaction between T and B cells and for normal
      antibody responses to T-cell-dependent antigens. To determine the physiological
      function of ICOS, we generated and characterized gene-targeted ICOS-deficient
      mice. In vivo, a lack of ICOS results in severely deficient T-cell-dependent B
      cell responses. Germinal centre formation is impaired and immunoglobulin class
      switching, including production of allergy-mediating IgE, is defective. ICOS
      deficient T cells primed in in vivo and restimulated in vitro with specific
      antigen produce only low levels of interleukin-4, but remain fully competent to
      produce interferon-gamma.

PMID- 11343124
TI  - Telomere looping permits gene activation by a downstream UAS in yeast.
AB  - In yeast (Saccharomyces cerevisiae), transcriptional activators, such as Gal4 and
      Gal4-VP16, work ordinarily from sites located in the upstream activating sequence
      (UAS) positioned about 250 base pairs upstream of the transcription start site.
      In contrast to their behaviour in mammalian cells, however, such activators fail
      to work when positioned at distances greater than approximately 600-700 base
      pairs upstream, or anywhere downstream of the gene. Here we show that, in yeast,
      a gene bearing an enhancer positioned 1-2 kilobases downstream of the gene is
      activated if the reporter is linked to a telomere, but not if it is positioned at
      an internal chromosomal locus. These observations are explained by the finding
      that yeast telomeres form back-folding, or looped, structures. Because yeast
      telomeric regions resemble the heterochromatin found in higher eukaryotes, these
      findings might also explain why transcription of some higher eukaryotic genes
      depends on their location in heterochromatin.

PMID- 11343125
TI  - Direct observation of DNA rotation during transcription by Escherichia coli RNA
      polymerase.
AB  - Helical filaments driven by linear molecular motors are anticipated to rotate
      around their axis, but rotation consistent with the helical pitch has not been
      observed. 14S dynein and non-claret disjunctional protein (ncd) rotated a
      microtubule more efficiently than expected for its helical pitch, and myosin
      rotated an actin filament only poorly. For DNA-based motors such as RNA
      polymerase, transcription-induced supercoiling of DNA supports the general
      picture of tracking along the DNA helix. Here we report direct and real-time
      optical microscopy measurements of rotation rate that are consistent with high
      fidelity tracking. Single RNA polymerase molecules attached to a glass surface
      rotated DNA for >100 revolutions around the right-handed screw axis of the double
      helix with a rotary torque of >5 pN nm. This real-time observation of rotation
      opens the possibility of resolving individual transcription steps.

PMID- 11343127
TI  - Complete mitochondrial DNA sequence of Conger myriaster (Teleostei:
      Anguilliformes): novel gene order for vertebrate mitochondrial genomes and the
      phylogenetic implications for anguilliform families.
AB  - The complete nucleotide sequence of the mitochondrial genome was determined for a
      conger eel, Conger myriaster (Elopomorpha: Anguilliformes), using a PCR-based
      approach that employs a long PCR technique and many fish-versatile primers.
      Although the genome [18,705 base pairs (bp)] contained the same set of 37
      mitochondrial genes [two ribosomal RNA (rRNA), 22 transfer RNA (tRNA), and 13
      protein-coding genes] as found in other vertebrates, the gene order differed from
      that recorded for any other vertebrates. In typical vertebrates, the ND6,
      tRNA(Glu), and tRNA(Pro) genes are located between the ND5 gene and the control
      region, whereas the former three genes, in C. myriaster, have been translocated
      to a position between the control region and the tRNA(Phe) gene that are
      contiguously located at the 5' end of the 12S rRNA gene in typical vertebrates.
      This gene order is similar to the recently reported gene order in four lineages
      of birds in that the latter lack the ND6, tRNA(Glu), and tRNA(Pro) genes between
      the ND5 gene and the control region; however, the relative position of the
      tRNA(Pro) to the ND6-tRNA(Glu) genes in C. myriaster was different from that in
      the four birds, which presumably resulted from different patterns of tandem
      duplication of gene regions followed by gene deletions in two distantly related
      groups of organisms. Sequencing of the ND5-cyt b region in 11 other anguilliform
      species, representing 11 families, plus one outgroup species, revealed that the
      same gene order as C. myriaster was shared by another 4 families, belonging to
      the suborder Congroidei. Although the novel gene orders of four lineages of birds
      were indicated to have multiple independent origins, phylogenetic analyses using
      nucleotide sequences from the mitochondrial 12S rRNA and cyt b genes suggested
      that the novel gene orders of the five anguilliform families had originated in a
      single ancestral species.

PMID- 11343128
TI  - The evolution of bioluminescent oxygen consumption as an ancient oxygen
      detoxification mechanism.
AB  - Endogenous reductants such as hydrogen sulfide and alkylthiols provided free
      radical scavenging systems during the early evolution of life. The development of
      oxygenic photosynthesis spectacularly increased oxygen levels, and ancient life
      forms were obliged to develop additional antioxidative systems. We develop here
      the hypothesis of how "prototypical" bioluminescent reactions had a plausible
      role as an ancient defense against oxygen toxicity through their "futile"
      consumption of oxygen. As oxygen concentrations increased, sufficient light would
      have been emitted from such systems for detection by primitive photosensors, and
      evolutionary pressures could then act upon the light emitting characteristics of
      such systems independently of their use as futile consumers of oxygen. Finally,
      an example of survival of this ancient mechanism in present-day bioluminescent
      bacteria (in the Euprymna scolopes-Vibrio fischeri mutualism) is discussed. Once
      increasing ambient oxygen levels reached sufficiently high levels, the use of
      "futile" oxygen consumption became too bioenergetically costly, so that from this
      time the evolution of bioluminescence via this role was made impossible, and
      other mechanisms must be developed to account for the evolution of
      bioluminescence by a wide range of organisms that patently occurred after this
      (e.g., by insects).

PMID- 11343129
TI  - Horizontal transfer of the photosynthesis gene cluster and operon rearrangement
      in purple bacteria.
AB  - A 37-kb photosynthesis gene cluster was sequenced in a photosynthetic bacterium
      belonging to the beta subclass of purple bacteria (Proteobacteria), Rubrivivax
      gelatinosus. The cluster contained 12 bacteriochlorophyll biosynthesis genes
      (bch), 7 carotenoid biosynthesis genes (crt), structural genes for photosynthetic
      apparatuses (puf and puh), and some other related genes. The gene arrangement was
      markedly different from those of other purple photosynthetic bacteria, while two
      superoperonal structures, crtEF-bchCXYZ-puf and bchFNBHLM-lhaA-puhA, were
      conserved. Molecular phylogenetic analyses of these photosynthesis genes showed
      that the photosynthesis gene cluster of Rvi. gelatinosus was originated from
      those of the species belonging to the alpha subclass of purple bacteria. It was
      concluded that a horizontal transfer of the photosynthesis gene cluster from an
      ancestral species belonging to the alpha subclass to that of the beta subclass of
      purple bacteria had occurred and was followed by rearrangements of the operons in
      this cluster.

PMID- 11343130
TI  - Amplification and phylogenetic relationships of a subfamily of blood, a
      retrotransposable element of Drosophila.
AB  - To get a better understanding of the effect of interelement selection on the
      variation of long terminal repeat retrotransposon families, we have investigated
      the evolutionary history of blood in the Drosophila melanogaster species complex.
      We carried out a PCR approach to amplify the 5' untranslated region from blood in
      the four species of the complex. This procedure revealed two main classes of size
      variants. Phylogenetic analyses of nucleotide sequences from these variants and
      blood elements from the Drosophila Genome Projects database show that elements
      are grouped according to their size, so that they probably correspond to two
      subfamilies. These two subfamilies arose prior to the split of the complex, and
      several facts indicate that the expansion of one of them is leading to the
      competitive exclusion of the other, at least from the euchromatic regions of the
      genome.

PMID- 11343131
TI  - Non-LTR retrotransposons encoding a restriction enzyme-like endonuclease in
      vertebrates.
AB  - All autonomous non-long terminal repeat (non-LTR) retrotransposons reported to
      date in vertebrates encode an apurinic/apyrimidinic endonuclease-like enzyme
      necessary for target sequence cleavage and subsequent target-primed reverse
      transcription. We describe here vertebrate non-LTR retrotransposons encoding
      another type of endonuclease more related to type IIS restriction enzymes. Such
      retrotransposons have been detected until now only in trypanosomes, nematodes,
      and arthropods. The retrotransposon Rex6 was identified in the genome of several
      teleost fish including Xiphophorus maculatus (platyfish), Oryzias latipes
      (medakafish), Oreochromis niloticus (Nile tilapia), and Fugu rubripes (Japanese
      pufferfish). Rex6 encodes a reverse transcriptase and a putative restriction
      enzyme-like endonuclease and is a member of the R4 family of non-LTR
      retrotransposons containing the Dong and R4 elements found in nematodes and
      insects. Rex6 was active in many species during teleost evolution and underwent
      several bursts of retrotransposition (some of them being relatively recent)
      leading to a high copy number of Rex6 in the genome of numerous fish. Extremely
      truncated Rex6-related sequences were detected by database screening in reptiles,
      including the snake Trimeresus flavoviridis and the lizard Anolis carolinensis,
      but not in sequences from the human genome project, suggesting that this element
      might have been lost from certain vertebrate lineages.

PMID- 11343132
TI  - Mutation and recombination in cattle satellite DNA: a feedback model for the
      evolution of satellite DNA repeats.
AB  - The cattle genome contains several distinct centromeric satellites with
      interrelated evolutionary histories. We compared these satellites in Bovini
      species that diverged 0.2 to about 5 Myr ago. Quantification of hybridization
      signals by phosphor imaging revealed a large variation in the relative amounts of
      the major satellites. In the genome of water buffalo this has led to the complete
      deletion of satellite III. Comparative sequencing and PCR-RFLP analysis of
      satellites IV, 1.711a, and 1.711b from the related Bos and Bison species revealed
      heterogeneities in 0.5 to 2% of the positions, again with variations in the
      relative amounts of sequence variants. Restriction patterns generated by double
      digestions suggested a recombination of sequence variants. Our results are
      compatible with a model of the life history of satellites during which
      homogeneity of interacting repeat units is both cause and consequence of the
      rapid turnover of satellite DNA. Initially, a positive feedback loop leads to a
      rapid saltatory amplification of homogeneous repeat units. In the second phase,
      mutations inhibit the interaction of repeat units and coexisting sequence
      variants amplify independently. Homogenization by the spreading of one of the
      variants is prevented by recombination and the satellite is eventually
      outcompeted by another, more homogeneous tandem repeat sequence.

PMID- 11343133
TI  - The level and landscape of optimization in the origin of the genetic code.
AB  - We consider a model of the origin of genetic code organization incorporating the
      biosynthetic relationships between amino acids and their physicochemical
      properties. We study the behavior of the genetic code in the set of codes subject
      both to biosynthetic constraints and to the constraint that the biosynthetic
      classes of amino acids must occupy only their own codon domain, as observed in
      the genetic code. Therefore, this set contains the smallest number of elements
      ever analyzed in similar studies. Under these conditions and if, as predicted by
      physicochemical postulates, the amino acid properties played a fundamental role
      in genetic code organization, it can be expected that the code must display an
      extremely high level of optimization. This prediction is not supported by our
      analysis, which indicates, for instance, a minimization percentage of only 80%.
      These observations can therefore be more easily explained by the coevolution
      theory of genetic code origin, which postulates a role that is important but not
      fundamental for the amino acid properties in the structuring of the code. We have
      also investigated the shape of the optimization landscape that might have arisen
      during genetic code origin. Here, too, the results seem to favor the coevolution
      theory because, for instance, the fact that only a few amino acid exchanges would
      have been sufficient to transform the genetic code (which is not a local minimum)
      into a much better optimized code, and that such exchanges did not actually take
      place, seems to suggest that, for instance, the reduction of translation errors
      was not the main adaptive theme structuring the genetic code.

PMID- 11343135
TI  - Proposal for an American Association of Pediatric Cardiology.

PMID- 11343134
TI  - Evolution of base composition and codon usage bias in the genus Flavivirus.
AB  - The extent to which base composition and codon usage vary among RNA viruses, and
      the possible causes of this bias, is undetermined in most cases. A maximum
      likelihood statistical method was used to test whether base composition and codon
      usage bias covary with arthropod association in the genus Flavivirus, a major
      source of disease in humans and animals. Flaviviruses are transmitted by
      mosquitoes, by ticks, or directly between vertebrate hosts. Those viruses
      associated with ticks were found to have a significantly lower G+C content than
      non-vector-borne flaviviruses and this difference was present throughout the
      genome at all amino acids and codon positions. In contrast, mosquito-borne
      viruses had an intermediate G+C content which was not significantly different
      from those of the other two groups. In addition, biases in dinucleotide and codon
      usage that were independent of base composition were detected in all
      flaviviruses, but these did not covary with arthropod association. However, the
      overall effect of these biases was slight, suggesting only weak selection at
      synonymous sites. A preliminary analysis of base composition, codon usage, and
      vector specificity in other RNA virus families also revealed a possible
      association between base composition and vector specificity, although with biases
      different from those seen in the Flavivirus genus.

PMID- 11343136
TI  - Alexander Sandor Nadas, M.D. (1913-2000).

PMID- 11343137
TI  - Feasibility of percutaneous transluminal coronary angioplasty to patients with
      Kawasaki Disease as an early management strategy.
AB  - We successfully performed percutaneous transluminal coronary angioplasty (PTCA)
      in three infants with Kawasaki disease ages 11 to 29 months. The time from the
      onset of disease to PTCA ranged from 6 to 21 months. On period reevaluation 12 to
      40 months after PTCA, they had no evidence of myocardial ischemia or restenosis.
      As an early management strategy, PTCA could be a good palliation to control
      myocardial ischemia associated with Kawasaki disease. From our study and a
      literature review, we suggest that PTCA may be more effective if it is performed
      earlier, even in young patients.

PMID- 11343138
TI  - Has the time arrived for PTCA in CAD following Kawasaki disease?

PMID- 11343139
TI  - Coronary blood flow assessed by transthoracic echocardiography in neonates.
AB  - Coronary flow measurement has provided useful clinical and physiologic
      information. However, there is little information about values for coronary flow
      in normal neonates, much less neonates with congenital heart disease. The aim of
      this study was to assess coronary blood flow in normal neonates and to compare
      the results with those in infants with ventricular septal defect. The study
      groups consisted of 12 normal neonates and 9 infants with simple ventricular
      septal defect associated with pulmonary hypertension. Left ventricular dimension,
      left ventricular mass, and the diameter of the coronary vessel were measured by
      standard M-mode and two-dimensional echocardiography. Peak flow velocities, flow
      velocity integrals, and flow volumes in the left anterior descending and
      circumflex coronary arteries were measured. The flow signals from the left
      anterior descending and circumflex coronary arteries were recorded in 84% (10/12)
      and 17% (2/12), respectively, in the normal neonates and 78% (7/9) and 11% (1/9),
      respectively, in the patients. The left ventricular end diastolic diameter and
      mass were significantly lower in normal infants than in the infants with
      ventricular septal defect (1.56 +/- 0.11 vs 1.84 +/- 0.09 cm and 5.4 +/- 1.6 vs
      8.8 +/- 0.8 g, respectively, p < 0.01). The mean peak diastolic velocity and the
      flow velocity time integral in the left anterior descending coronary artery were
      significantly lower in the normal neonates than in the patients (15 +/- 4 vs 28
      +/- 6 cm/sec and 2.3 +/- 0.6 vs 5.9 +/- 1.5 cm, respectively, p < 0.01). The
      coronary flow volume was significantly lower in the normal neonates than in the
      patients (3.1 +/- 1.4 vs 7.9 +/- 4.7 ml/min, p < 0.05). However, the flow volume
      of the left anterior descending coronary artery/left ventricular mass did not
      show any significant difference between the two groups. Our study demonstrated in
      neonates that it is feasible to detect noninvasively and to evaluate the flow of
      the left anterior descending coronary artery under physiologic conditions and
      abnormal hemodynamic situations. Increased flow volume in the left anterior
      descending coronary artery in patients with ventricular septal defect may be a
      compensated mechanism for the increase in oxygen demand of hypertrophic
      myocardium of the left ventricle.

PMID- 11343140
TI  - Surgical cutdown of the right carotid artery for aortic balloon valvuloplasty in
      infancy: midterm follow-up.
AB  - A vascular approach for balloon aortic dilatation in infants is of major concern
      due to the high risk of femoral artery injury. To overcome this problem, a
      surgical right carotid artery (RCA) approach has been advocated. No reports are
      available on RCA after neonatal cutdown. Since 1990, RCA cutdown has been
      performed in 29 infants with congenital aortic stenosis. Periprocedural
      complications included one asymptomatic occlusion and one transient trauma of the
      stellate ganglion. At a mean follow-up of 4.4 +/- 2.2 years from aortic
      valvuloplasty, ultrasound assessment of morphology and flow of RCA was performed
      in 17 children. RCA was patent in all patients. The mean ratio of right/left
      carotid artery diameter was 0.95 +/- 0.16 (range 0.65-1.2). The site of surgical
      incision could be identified in 5 children in the absence of flow disturbance. A
      6-year-old asymptomatic girl, who underwent two procedures, had a 35% reduction
      of RCA diameter at the site of cannulation and turbulent flow at Doppler
      interrogation, indicating mild obstruction. Our data demonstrate that RCA is well
      preserved after neonatal surgical cutdown; asymptomatic obstruction can
      occasionally be present.

PMID- 11343141
TI  - Age dependency of stiffness of the abdominal aorta and the mechanical properties
      of the aorta in Kawasaki disease in children.
AB  - Measuring aortic distensibility has been shown to be useful in adults as a
      noninvasive method in the early detection of atherosclerosis. This study had two
      purposes: to assess the stiffness of the abdominal aorta by using two-dimensional
      echocardiography (2DE) in healthy neonates, children, and adults and to assess
      aortic distensibility in children with Kawasaki disease in acute and subacute
      phases. The study comprised 168 healthy subjects and 40 patients with Kawasaki
      disease. We recorded systolic (Ps) and diastolic (Pd) blood pressure and measured
      aortic diameter (Dd) at both minimum diastolic pressure and maximum systolic
      expansion (Ds) by 2DE. These measurements were used to determine (1) aortic
      strain (S) = (Ds - Dd)/Dd, (2) pressure strain elastic modulus (Ep) = (Ps -
      Pd)/S, and (3) normalized Ep (Ep*) = Ep/Pd. Significant correlations were found
      between S and age, Ep and age, and Ep* and age. In Kawasaki disease, Ep and Ep*
      showed negative correlations to day after onset. The aorta was less distensible
      in infants, became soft in 12- to 16-year-olds, and then stiffened with
      increasing age among normal subjects. In Kawasaki disease, aortic stiffness was
      high at the acute phase and normal at the subacute phase. These tendencies may be
      related to the biological characteristics of smooth muscle cells.

PMID- 11343142
TI  - Around Pediheart: angiographic measurements.

PMID- 11343143
TI  - Access to the left atrium for delivery of radiofrequency ablation in young
      patients: retrograde aortic vs transseptal approach.
AB  - Reported experience with the transseptal approach to the left atrium for delivery
      of radiofrequency energy in the young patient is limited. To compare two
      approaches for radiofrequency ablation (RFA) in the left atrium we reviewed our
      experience from January 1, 1991, through February 1, 1999, in 154 procedures
      performed on 136 patients (mean age 12.2 years). The patients were grouped by
      either the retrograde aortic route (R, n = 30) or the transseptal atrial route
      (T, n = 106). No significant differences were found in age, weight, height,
      supraventricular tachycardia cycle length, or electrocardiograph characteristics
      (manifest vs concealed accessory pathway) between the two approaches. Comparison
      of the transseptal group to the retrograde aortic group revealed a significant
      difference in the number of catheters (mean = 4 R vs 3 T, p < 0.0001), total
      fluoroscopic time (71.3 min R vs 43.0 min T, p = 0.0007), diagnostic fluoroscopic
      time (40.2 min R vs 16.6 min T, p < 0.0001), ablation fluoroscopic time (44.7 min
      R vs 25.3 min T, p = 0.019), and procedure time (5.0 hours R vs 4.1 hours T, p <
      0.0001). No significant difference was found in success rate, number of
      radiofrequency applications, or major complication rate. These data suggest that
      although outcomes and major complication rates are similar for the two groups,
      the use of fewer catheters and shorter fluoroscopic times warrant consideration
      of the transseptal atrial approach in young patients.

PMID- 11343144
TI  - Assessment of progressive changes in exercise performance in patients with a
      systemic right ventricle following the atrial switch repair.
AB  - There is a high prevalence of right ventricular dysfunction and reduced exercise
      performance in survivors of atrial switch repair for transposition of the great
      arteries. However, it is not known whether the impairment in exercise performance
      is progressive. We performed paired comparison of exercise performance in 28
      patients who underwent two serial incremental exercise tests at an interval of
      5.0 +/- 1.4 years between the two tests (age 11.5 +/- 3.7 years at first test,
      16.4 +/- 3.6 years at second test). There was no change in the chronotropic
      response between the two tests. However, there was a reduction in both the peak
      VO2 (32.5 +/- 8.3 vs 29.6 +/- 5.7 ml/kg/min, p = 0.05) and anerobic threshold
      (22.1 +/- 5.1 vs 18.3 +/- 4.2 ml/kg/min, p < 0.01) with time. Furthermore, there
      was a decline in the O2 pulse (oxygen uptake/beat) at anaerobic threshold (%
      predicted value 95 +/- 23% vs 82 +/- 23%, p =.02), O2 pulse at a heart rate of
      140 (% predicted value 100 +/- 30% vs 85 +/- 19%, p = 0.02), and the maximum O2
      pulse (z value -0.27 +/- 1.31 vs -1.27 +/- 1.16, p < 0.01) when compared to
      growth-related normal values. We conclude that there is a progressive reduction
      in aerobic response to exercise in patients with a systemic right ventricle. The
      maintenance of chronotropic response suggests that the stroke volume response of
      the systemic right ventricle during exercise does not increase commensurate with
      somatic growth.

PMID- 11343145
TI  - Right ventricular dilatation in the fetus: a study of associated features and
      outcome.
AB  - Right ventricular dilatation is an infrequent finding at fetal echocardiography.
      Previous studies have documented an association with aortic coarctation. However,
      there are associations with other congenital abnormalities. We reviewed our
      experience of fetal right heart dilatation in order to recognize concurrent
      anomalies and to assess the outcome of the affected fetuses. We studied all
      fetuses with right ventricular dilatation over a 5-year period. We documented
      associated cardiac and noncardiac lesions, and outcome data were assessed in
      terms of the number of fetuses that were born live and the number surviving to 2
      months of age. Forty-three fetuses with right heart dilatation were seen. Fifteen
      had associated cardiac abnormalities: most commonly coarctation (n = 4) and VSD
      (n = 4). Seven had associated noncardiac abnormalities. There were seven fetuses
      who also had chromosomal abnormalities. In total, there were three terminations
      of pregnancy, four intrauterine deaths, one stillbirth and 35 live-births. Twenty
      eight were alive at 2 months of age (70% of the nonterminated pregnancies). Fetal
      right heart dilatation is frequently associated with both cardiac and noncardiac
      congenital abnormalities. Our outcome figures suggest a guarded prognosis be
      given during counseling of parents of fetuses with right heart dilatation.

PMID- 11343146
TI  - Heart size on chest x-ray as a predictor of cardiac enlargement by
      echocardiography in children.
AB  - To determine the usefulness of heart size on chest radiograph (CXR) in predicting
      cardiac enlargement (CE) in children, we prospectively evaluated 95 consecutive
      outpatients, who had both a CXR and echocardiography performed. Their median age
      was 5.0 years (2 days to 19.9 years). All patients underwent CXR assessment by a
      pediatric radiologist, with classification of cardiac silhouette as normal,
      borderline, or enlarged. Echocardiographic assessment of CE was performed by a
      pediatric echocardiographer. Sensitivity, specificity, and predictive values of
      the pediatric radiologist's interpretation of heart size on CXR were estimated.
      The presence of CE by echocardiography was used as the gold standard. Seventy
      nine patients (83.2%) had no CE on CXR, and 16 patients (16.8%) had CE.
      Sensitivity of the CXR to identify CE was 58.8%, 95% confidence interval (CI)
      [32.9, 81.6], with a positive predictive value of 62.5% [35.4, 84.8]. Specificity
      was 92.3% [84.0, 97.1], with a negative predictive value of 91.1% [82.6, 96.4].
      These data suggest that the assessment of CE on CXR to predict CE by
      echocardiography has a relatively high specificity and negative predictive value,
      but a low sensitivity and positive predictive value. The limitations of CXR as a
      diagnostic test should be understood by clinicians using the test when screening
      children for cardiac disease.

PMID- 11343147
TI  - Around Pediheart: rest and rheumatic fever.

PMID- 11343148
TI  - Iodixanol pharmacokinetics in children.
AB  - The objective of this report was to study the elimination pharmacokinetics of
      iodixanol in children. Iodixanol (Visipaque, Nycomed Inc., Wayne, PA, USA) is a
      new iso-osmolar iodinated radiocontrast agent. We hypothesized that elimination
      of this agent would be dependent on age-related differences in renal clearance.
      Seven centers enrolled 43 patients. Cardiac catheterization was performed in 41
      patients and cranial computed tomography in 2. Patients were entered into 5 age
      groups: newborn to <2 months, 2 to <6 months, 6 months to <1 year, 1 to <3 years,
      and 3 to <or=12 years. Plasma samples were obtained before and at 4 time periods
      after completion of iodixanol injection: 0.75-1.25 hours, 2-4 hours, 8-12 hours,
      and 16-32 hours. Plasma concentrations of iodixanol were determined using high
      performance liquid chromatography. The primary pharmacokinetic endpoint was the
      terminal elimination rate constant (kel). Data were complete for 40 patients,
      showing mean kel significantly lower in newborn to <2-month-old patients vs older
      patients: (h-1, mean +/- standard deviation [SD]): newborn to <2 months 0.185 +/-
      0.060, 2 to <6 months, 0.256 +/- 0.046, 6 months to <1 year 0.299 +/- 0.042, 1 to
      <3 years 0.322 +/- 0.058, and 3 to <or=12 years 0.307 +/- 0.071; with increasing
      age, excretion is more rapid, as shown by each age group's elimination half-life
      (t1/2 beta) (h) 4.14 +/- 1.41, 2.79 +/- 0.55, 2.36 +/- 0.37, 2.23 +/- 0.51, and
      2.36 +/- 0.52, respectively. Iodixanol has elimination in children >6 months of
      age that is comparable to normal adults. Prolonged elimination in children <6
      months of age is related to renal immaturity.

PMID- 11343149
TI  - Balloon angioplasty of right ventricular outflow tract conduits.
AB  - Palliation of complex congenital heart disease, requiring reconstruction of the
      right ventricular outflow tract (RVOT), is standard practice. Survival of the
      homograft is a limiting factor. We examined the role of balloon angioplasty (BAP)
      in prolonging conduit life. Twelve patients underwent 15 BAP procedures between
      February 1989 and October 1997. The median age at conduit insertion was 28 months
      with detection of a significant echo gradient 42 months later. Calcification of
      homografts, with attendant obstruction and valve dysfunction, was present in all
      patients. BAP was performed within 1 month of echocardiography and reduced the
      gradient from a median of 57 to 38 mmHg (p < 0.0005). Echocardiographic follow-up
      showed persistent gradients (median 68 mmHg) and 11/12 patients went on to
      conduit replacement after BAP. Only one patient had replacement deferred as a
      result of BAP. Complications requiring intervention occurred in 20% of the
      procedures and included bleeding and an unusual balloon fracture. Although BAP
      can reduce the pressure gradient across the RVOT conduit, the effect is transient
      and the delay of surgery is not due to improved hemodynamic function.
      Approximately 10% of cases will benefit from BAP alone, but given the high rate
      of complications, we do not recommend this procedure as a means of prolonging
      conduit life.

PMID- 11343151
TI  - Around Pediheart: exercise syncope.

PMID- 11343150
TI  - Pressure-regulated volume control vs volume control ventilation in infants after
      surgery for congenital heart disease.
AB  - The objective of this investigation was to compare how two modes of positive
      pressure ventilation affect cardiac output, airway pressures, oxygenation, and
      carbon dioxide removal in children with congenital heart disease in the immediate
      postoperative period. The investigation used a one group pretest-post-test study
      design and was performed in the pediatric cardiac intensive care unit in a
      university-affiliated children's hospital. Nine infants were enrolled immediately
      after repair of tetralogy of Fallot (2) or atrioventricular septal defects (7)
      with mean weight = 5.5 kg (4.2-7.3 kg). Children were admitted to the pediatric
      cardiothoracic intensive care unit after complete surgical repair of their
      cardiac defect and stabilized on a Siemen's Servo 300 ventilator in volume
      control mode (VCV1) (volume-targeted ventilation with a square flow wave
      pattern). Tidal volume was set at 15 cc/kg (total). Hemodynamic parameters,
      airway pressures and ventilator settings, and an arterial blood gas were
      measured. Patients were then changed to pressure-regulated volume control mode
      (PRVC) (volume-targeted ventilation with decelerating flow wave pattern) with the
      tidal volume set as before. Measurements were repeated after 30 minutes. Patients
      were then returned to volume control mode (VCV2) and final measurements made
      after 30 minutes. The measurements and results are as follows: After correction
      of congenital heart defects in infants, mechanical ventilation using a
      decelerating flow wave pattern resulted in a 19% decrease in peak inspiratory
      pressure without affecting hemodynamics, arterial oxygenation, or carbon dioxide
      removal.

PMID- 11343152
TI  - Early postoperative results after total correction of tetralogy of fallot in
      older patients: is primary repair always justified?
AB  - The objective of this study was to compare early postoperative results in primary
      vs 2-stage repair of tetralogy of Fallot in patients operated on after 5 years of
      age. Eighty-four patients with tetralogy of Fallot were studied, who were more
      than 5 years of age and who were repaired in one center by one surgeon. Hospital
      death and ratio of right-to-left ventricle pressure after correction were
      compared between the primary and the 2-stage groups as early outcome indices.
      Overall hospital mortality was 11.9% (10/88). There were 9 (18.4%) hospital
      deaths in the primary and 1 (2.9%) in the 2-stage group. Mortality was
      significantly higher in the primary group (p = 0.04 using the 2-tailed Fisher's
      exact test; relative risk = 6.43; 95% CI = 0.85-48.46). The mean +/- standard
      deviation (SD) for RV/LV ratio was 0.51 +/- 0.13. It was 0.61 +/- 0.11 in
      patients who died and 0.49 +/- 0.12 in patients who lived (p = 0.01 using the 2
      tailed t-test). RV/LV ratio was not significantly different between either group.
      In the 2-stage group, there was a small inverse correlation between the time
      interval and the RV/LV ratio (correlation coefficient = -0.235). The TAP group
      had a statistically significant lower time interval between shunt and total
      correction than the RVOT-P group (p = 0.02 using 2-tailed t-test). Older patients
      generally do better on 2-stage repair, because of their age. A long period of low
      pulmonary blood flow has induced unbalanced ventricles and exaggerated RVOTO for
      these patients because of muscle hypertrophy. In such patients, shunting will
      prepare the left ventricle for accepting the extra blood volume that will reach
      the left ventricle after total correction.

PMID- 11343153
TI  - Cardiac ventricular aneurysm in a child.
AB  - Cardiac ventricular aneurysms are anomalous developments that are multifactorial
      in origin. Few pediatric cases have been cited. The majority of the cited cases
      have had negative consequences. We report an asymptomatic boy with an aneurysm
      incidentally found, and his identical twin brother with no evidence of aneurysm.

PMID- 11343154
TI  - Elongation of the aorta and multiple cardiovascular abnormalities associated with
      larsen syndrome.
AB  - Larsen syndrome is a genetically heterogeneous group of disorders characterized
      by multiple joint dislocations and a characteristic face. We describe a girl with
      the typical features of Larsen syndrome. She also had associated multiple
      cardiovascular anomalies. The anomalies included elongation of the aorta,
      bicuspid aortic valve, subaortic stenosis, mitral valve prolapse with mitral
      regurgitation, atrial septal defect of the secundum type, and a patent ductus
      arteriosus.

PMID- 11343155
TI  - Ventricular aneurysm complicating neonatal coxsackie B4 myocarditis.
AB  - A premature neonate suffered from disseminated Coxsackie B4 infection.
      Myocarditis and a coexisting persistent ductus arteriosus became complicated with
      recurrent atrial tachycardia and severe heart failure. She survived with
      satisfactory cardiac function. Ventricular aneurysm was detected on follow-up
      echocardiography.

PMID- 11343156
TI  - Around Pediheart: neonatal bradycardia.

PMID- 11343157
TI  - Ventricular tachycardia induced by supraventricular extrasystoles.
AB  - Electrocardiography was performed in a newborn boy without organic heart disease,
      in whom supraventricular extrasystoles with varying coupling were seen. The
      supraventricular extrasystoles were occasionally followed by ventricular
      extrasystoles. The coupling intervals of ventricular extrasystoles to the
      preceding supraventricular extrasystoles were also considerably variable.
      Ventricular tachycardia occurred following comparatively late coupled ventricular
      extrasystoles. This is the first known report on ventricular tachycardia
      following comparatively late coupled ventricular extrasystoles in a newborn
      infant. This strengthens our previous suggestion that such ventricular
      tachycardia can be caused by longitudinal dissociation in the reentrant pathway
      of extrasystoles.

PMID- 11343158
TI  - "Cobra-like" deformation of an Amplatzer septal occluder.
AB  - Transcatheter occlusion of secundum atrial septal defects using Amplatzer septal
      occluders (ASOs) is a safe, simple, and effective alternative to surgical
      closure. We present the first report of a "cobra-like" shape deformation of the
      device encountered during inappropriate positioning. The complication is
      reversible and is easily avoidable.

PMID- 11343159
TI  - Successful surgical repair of common pulmonary vein atresia in a newborn.
AB  - A 7-hour-old boy underwent an emergency operation with an anticipated diagnosis
      of total anomalous pulmonary venous connection. The precise diagnosis of common
      pulmonary vein atresia (CPVA) was made during the operation. A side-to-side
      anastomosis between the common pulmonary venous chamber and the left atrium was
      performed. All procedures were successfully carried out on the beating heart
      under the cardiopulmonary bypass. A tentative diagnosis of CPVA should always be
      borne in minds in neonates with clinical conditions such as deep cyanosis
      unresponsive to the oxygen therapy, stubborn acidosis, severe pulmonary venous
      congestion, and rapid deterioration. The corrective repair of CPVA with the heart
      beating appears to be the procedure of choice in the setting of seriously damaged
      myocardium of the immature heart. To the best of our knowledge, this is the
      youngest survivor of the corrective surgery for CPVA and operation at time of
      diagnosis is the important principle.

PMID- 11343160
TI  - Malignant fibrosarcoma with features of myxoma.
AB  - Left atrial tumor, diagnosed as myxoma at first investigation, was later
      demonstrated to be a malignant fibrosarcoma with myxoid change. Myxoma should be
      diagnosed and managed carefully because of its wide range of histopathologic
      features.

PMID- 11343161
TI  - Monozygotic twins with chromosome 22q11 microdeletion and discordant phenotypes
      in cardiovascular patterning.
AB  - Monozygotic twins with chromosome 22q11 microdeletions offer an ideal situation
      to observe the association of microdeletion and disrupted cardiovascular
      patterning. We report monozygotic twins concordant for 22q11.2 microdeletion but
      discordant for cardiovascular patterning. Both twins showed identical
      intracardiac defects including tetralogy of Fallot with pulmonary atresia.
      Nevertheless, their great vessel patternings were variable. These twins show that
      the mispatterning of the great vessels may not correlate with intracardiac
      morphogenesis. The discordant development of the great vessels, especially in the
      pulmonary vascular system, has clinical significance for prognosis. The
      phenotypic variability of cardiovascular anomalies seen in 22q11 microdeletion
      cannot be explained on the basis of genotypic difference.

PMID- 11343165
TI  - Advances in General Thoracic Surgery: Introduction.

PMID- 11343166
TI  - To the Editor.

PMID- 11343167
TI  - To the Editor.

PMID- 11343168
TI  - Reply.

PMID- 11343169
TI  - To the Editor.

PMID- 11343170
TI  - Reply.

PMID- 11343171
TI  - To the Editor.

PMID- 11343172
TI  - Vagus.

PMID- 11343173
TI  - Enhanced expression of matrix metalloproteinase-9 in abdominal aortic aneurysms.
AB  - Abdominal aortic aneurysms (AAAs) are characterized by structural alterations of
      the aortic wall resulting from degradation of collagen and elastin. Matrix
      metalloproteinases (MMPs), particularly MMP-2 and MMP-9, show strong
      elastinolytic activity. We examined the levels of mRNA for MMP-2, MMP-9, membrane
      type (MT)-MMP-1, tissue inhibitor of metalloproteinase-1 (TIMP-1), and TIMP-2 in
      AAAs (n = 8), atherosclerotic occlusive diseases (AOD) (n = 8), and normal
      subjects (n = 8) using the reverse transcription-polymerase chain reaction (RT
      PCR). We also analyzed the gelatinolytic activity of these metalloproteinases
      using gelatin zymography. The levels of MMP-2 and MMP-9 mRNA were increased in
      the AAA group compared with those in the AOD group and normal subjects. The
      levels for TIMP-1 and TIMP-2 mRNA in the AAA group were also higher than those in
      the AOD and normal groups. Only in the case of MT-MMP-1 was the difference
      between AAA and AOD not statistically significant. By gelatin zymography with the
      same samples used for RT-PCR, gelatinolytic activity of MMP-9 was elevated in all
      AAA tissues. The 62-kDa form of MMP-2 was elevated in both the AAA and AOD groups
      and did not differ significantly between them. Linear regression analysis
      demonstrated a significant positive correlation between mRNA levels of MMPs and
      those of TIMPs. These observations suggest that aneurysm formation in patients
      with atherosclerosis is related to the degree of MMP-9 expression.

PMID- 11343174
TI  - Analysis of 100 consecutive hepatectomies: risk factors in patients with liver
      cirrhosis or obstructive jaundice.
AB  - We analyzed various pre-, intra-, and postoperative variables in 100 consecutive
      patients treated by hepatectomy for various malignant and benign liver diseases
      to identify patients at risk of developing postoperative complications. Patients
      were divided into three groups: those with normal liver (NL, n = 53); those with
      liver cirrhosis (LC, n = 32); and those with obstructive jaundice (OJ, n = 15).
      The overall postoperative morbidity and mortality rates were 14% and 4% (due to
      liver failure), respectively. In the LC group the combined presence of abnormal
      levels of serum hyaluronic acid (HA, > 200 ng/ml), indocyanine green retention
      rate at 15 minutes (ICGR15, > 15%), and hepatic uptake ratio of (99m)Tc
      galactosyl human serum albumin (GSA) at 15 minutes (LHL15, < 0.9) preoperatively
      was found to be a risk factor with a 100% morbidity rate. Operative blood loss of
      more than 1000 ml in LC patients was associated with high morbidity. In the OJ
      group preoperative parameters were almost normal after biliary drainage, but the
      extent of liver resection, blood loss > 2000 ml, and high serum interleukin-6 12
      hours after hepatectomy correlated with high postoperative morbidity. No
      morbidity or mortality was reported in the NL group, except in a single patient
      who received long-term intraarterial chemotherapy preoperatively. Consequently,
      the extent of hepatectomy should be carefully determined according to the
      preoperative risk factors in LC patients; and in OJ patients hepatectomy, which
      tends to become extensive, should be carefully performed to minimize surgical
      stress because preoperative factors do not help predict outcome. Furthermore, the
      present study revealed that a serum HA level higher than 500 ng/ml on
      postoperative day 1 or day 7 (or both) was a useful marker for hepatic failure.

PMID- 11343175
TI  - Loop ileostomy versus loop colostomy for defunctioning low anastomoses during
      rectal cancer surgery.
AB  - Several studies have compared loop ileostomy with loop colostomy to defunction
      colorectal anastomoses. The discordant results may be due to the heterogeneity of
      the indications. We therefore performed a retrospective study to compare the two
      procedures in a homogeneous group of patients operated on electively for rectal
      cancer. Among 462 consecutive patients undergoing rectal resection for cancer
      during 1986-1998, 60 had a loop colostomy and 107 a loop ileostomy to defunction
      a low anastomosis. The two groups were similar with respect to age, gender,
      obesity, tumor stage, and duration before closure (109 vs. 104 days; p = 0.28).
      All the stoma-related complications that occurred after construction and after
      closure of the stoma were recorded. There were no stoma-related deaths in the two
      groups. After stoma construction, the morbidity rate was significantly higher
      following loop colostomy than after loop ileostomy (35% vs. 19%; p = 0.02). After
      stoma closure the complication rate was significantly higher in the colostomy
      group than in the ileostomy group (34% vs. 12%; p = 0.004). The risk of surgical
      reintervention related to the morbidity of both construction and closure of the
      stoma was twice as high after loop colostomy than after loop ileostomy (22% vs.
      9%; p = 0.03). The results of this study showed that, in our experience, the
      overall stoma-related morbidity and risk of reoperation were significantly lower
      after loop ileostomy than after loop colostomy. This suggests that loop ileostomy
      is the best procedure for defunctioning colorectal anastomoses electively. We
      therefore recommend using a loop ileostomy during rectal cancer surgery.

PMID- 11343176
TI  - Role of esophagectomy in treatment of esophageal carcinoma with clinical evidence
      of adjacent organ invasion.
AB  - With carcinoma of the thoracic esophagus, clinical evidence of invasion of
      adjacent organs (T4) indicates a highly advanced stage, and most surgeons avoid
      esophagectomy. Although the therapeutic strategy for such disease is generally
      selected based on preoperative evaluation and intraoperative inspection, their
      accuracy and the relation to survival outcomes after esophagectomy have seldom
      been analyzed on the basis of exact histopathologic evidence. We performed
      esophagectomy, with perioperative adjuvant therapy when possible, on patients
      with clinical-T4 tumors unless absolutely unresectable conditions were detected.
      Among the 500 patients who underwent esophagectomy, the 78 patients whose tumors
      were confirmed to be T4 pathologically were compared with patients whose tumors
      were assessed as T4 preoperatively or intraoperatively to evaluate the role of
      esophagectomy for clinical-T4 carcinoma. Esophagectomy was possible for 99% of
      the pathologic-T4 tumors preoperatively assessed as resectable, but the resection
      was grossly incomplete in 35%. The true-positive rates in tumors preoperatively
      and intraoperatively assessed as T4 were 51% and 84%, respectively. The hospital
      mortality rate in patients with pathologic-T4 tumors was 4%. The overall 5-year
      survival rate for patients with pathologic-T4 tumors was 14%, compared with 60%
      for those with tumors assessed as T4 intraoperatively but not pathologically.
      Esophagectomy with perioperative adjuvant therapy yielded occasional cure with an
      acceptable mortality rate for patients with pathologic-T4 tumors assessed as
      technically resectable. Preoperative assessment and intraoperative macroscopic
      inspection had limitations for predicting pathologic-T4 disease and incomplete
      resection. Only patients with definitive evidence of unresectability should be
      excluded from esophagectomy.

PMID- 11343177
TI  - Expression of telomerase-associated genes: reflection of telomerase activity in
      gastric cancer?
AB  - Telomerase activation is a characteristic of immortalized tumor cells but not of
      normal cells. Telomerase activity has been detected in approximately 85% of
      malignant tumors, and assaying for telomerase activity is thought to be useful
      for diagnosing cancer. Three telomerase-associated molecules [human telomerase
      RNA component (hTR), telomerase-associated protein (TEP1), and human telomerase
      reverse transcriptase (hTERT)] have been cloned. We semiquantitatively measured
      telomerase activity and the expression of these genes in cancerous and
      noncancerous regions of gastric cancer patients. We also investigated whether the
      expression of these genes correlated with telomerase activity. Telomerase
      activity in cancerous regions was significantly higher than in noncancerous
      regions, but there was no correlation between telomerase activity and the
      expression of these genes. Furthermore, no clear difference was observed between
      cancerous and noncancerous regions. These data indicate that the level of three
      telomerase-associated genes (i.e., hTR, TEP1 mRNA, hTERT mRNA), do not reflect
      telomerase activity, and the RNA levels of these genes are not useful markers for
      diagnosing gastric cancer.

PMID- 11343178
TI  - Surgery and prognostic factors for gastric stromal tumor.
AB  - Morphologic studies of gastric stromal tumors (GSTs) indicate that mitotic counts
      (MCs) and tumor size are major discriminants predictive of biologic behavior. The
      purpose of this study is to improve the understanding of GST behavior, including
      the prognostic factors and surgical treatment of GSTs. A retrospective analysis
      (1990--1997) of the clinical course for 116 patients with GSTs was completed,
      with a median follow-up of 43 months. Tumors were categorized as malignant GSTs
      (n = 17) when the MC was > 5/50 high-power fields (HPF) and the size > 5 cm or as
      benign GSTs (n = 99) when the MC was < or = 5/50 HPF and the size < or = 5 cm, MC
      < or = 5/50 HPF and size > 5 cm, or MC > 5/50 HPF and size < or = 5 cm. None of
      99 benign tumors recurred or metastasized, whereas 7 of 17 malignant tumors
      recurred. MCs had a close correlation with tumor size. Immunohistochemical
      studies using CD34, smooth muscle actin, S-100 protein, and synaptophysin have
      shown positive rates of 61%, 33%, 14%, and 3%, respectively. Smooth muscle actin
      reactivity was more common in the benign tumors (p = 0.046) and synaptophysin
      reactivity in the malignant tumors (p = 0.010). Univariate analysis showed that
      the following clinicopathologic factors were potentially related to poor survival
      of patients: (1) MC > 5/50 HPF (p = 0.0001); (2) severe pleomorphism (p =
      0.0062); (3) necrosis (p = 0.0173); (4) marked cellularity (p = 0.0112); (5)
      presence of ulceration of overlying gastric mucosa (p = 0.0091); (6) tumor size >
      5 cm (p = 0.0195); and (7) exogastric growth pattern (p = 0.0344). Tumors with MC
      > 5/50 HPF and size > 5 cm were found to be strong indicators of an unfavorable
      prognosis. The type of surgery and tumor site did not affect the prognosis of the
      patients.

PMID- 11343179
TI  - Bedside percutaneous tracheostomy: clinical comparison of Griggs and Fantoni
      techniques.
AB  - Elective tracheostomy is widely considered the preferred airway management of
      patients on long-term ventilation. In addition to open tracheostomy, a number of
      percutaneous procedures have been introduced during the last two decades, among
      them techniques according to Griggs (guidewire dilating forceps, or GWDF) and to
      Fantoni (translaryngeal tracheostomy, or TLT). The aim of the study was to
      evaluate these two techniques in terms of perioperative complications, risks, and
      benefits in critically ill patients. A series of 100 critically ill adult
      patients on long-term ventilation underwent elective percutaneous tracheostomy,
      either according to the Griggs (n = 50) or Fantoni (n = 50) technique.
      Tracheostomy was performed under general anesthesia at the patient's bedside. The
      mean (+/-SD) operating times were short, 9.2 +/- 3.9 minutes (TLT) and 4.8 +/-
      3.7 minutes (GWDF) on average. Perioperative complications were noted in 4% of
      patients during either TLT or GWDF and included massive bleeding, mediastinal
      emphysema, posterior tracheal wall injury, and pretracheal placement of the
      tracheostomy tube. With regard to oxygenation, pre- and postoperative arterial
      oxygen tension divided by the fraction of inspired oxygen (PaO2/FiO2) ratios did
      not vary significantly, and no perioperative hypoxia was noted regardless of the
      technique used. We conclude that both TLT and GWDF represent attractive, safe
      alternatives to conventional tracheostomy or other percutaneous procedures if
      carefully performed by experienced physicians and under bronchoscopic control.

PMID- 11343180
TI  - Clinical relevance of vascular endothelial growth factor for thyroid neoplasms.
AB  - Angiogenesis is of vital importance during the development and progression of
      solid tumors. Vascular endothelial growth factor (VEGF) is a major regulator of
      angiogenesis and could be produced by some cancer cells. To investigate the
      clinical relevance of VEGF in the tumorigenesis of human thyroid, an
      immunohistochemical study was performed on archival materials of follicular
      adenomas (n = 13), Hurthle cell adenomas (n = 6), papillary carcinomas (n = 76),
      follicular carcinomas (n = 12), Hurthle cell carcinomas (n = 2), and anaplastic
      carcinomas (n = 8). Patterns of VEGF expression were analyzed in relation to
      histologic subtypes of thyroid tumors and were correlated to biologic indicators
      of papillary carcinoma. All papillary carcinomas and Hurthle cell neoplasms
      revealed a strong, diffuse staining reaction, whereas anaplastic carcinoma
      usually exhibited weak and infrequent immunoreactivity. VEGF levels were usually
      higher in follicular adenomas than in follicular carcinomas. With regard to
      prognostic value, VEGF expression did not correlate with tumor size, extent of
      invasion, or scores on the AGES system (i.e., patient age, tumor size, histologic
      grade, tumor extent, distant metastasis) or the MACIS system (i.e., metastasis,
      age, completeness of resection, invasion, tumor size) for papillary carcinomas (p
      > 0.05, respectively). The results of the current study indicate that VEGF may
      play a role in the development of human thyroid cancer. Determination of the
      angiogenic phenotype may have limited prognostic value for patients with
      papillary carcinoma.

PMID- 11343181
TI  - Total thyroidectomy for benign thyroid disorders in an endemic region.
AB  - Total thyroidectomy is increasingly being accepted as a treatment of choice for
      differentiated thyroid cancer. However, because of presumed increased morbidity
      associated with this procedure, it is still not considered a viable option for
      management of benign thyroid disorders. To assess the safety and efficacy of
      total thyroidectomy for management of benign thyroid disorders, we analyzed our
      data from 127 total thyroidectomies performed for benign thyroid disorders.
      Demographic details, biochemical findings, indications for operation, specimen
      weight, and complications were noted. Among these patients, 52 had a toxic goiter
      and 75 had a nontoxic goiter. The mean duration of the goiters being present was
      6.08 +/- 6.06 years (0.9--26.0 years), and the mean weight of the specimens was
      136.88 +/- 120.68 g. The incidence of occult malignancy was 6.3% (n = 8), and
      those of permanent hypothyroidism and permanent recurrent laryngeal nerve palsy
      were 1.6% and 0.8%, respectively. Total thyroidectomy should be considered a
      treatment of choice for multinodular goiter and Graves' disease in a setting of
      palpable nodule(s) or ophthalmopathy (or both). It is particularly relevant in
      endemic regions where patients present with a long-standing, large nodular goiter
      with virtually no normal thyroid tissue. Reoperation for recurrent goiter in such
      a setting would be fraught with distressing complications.

PMID- 11343183
TI  - Percutaneous recanalization of peripheral arterial occlusions.
AB  - The aim of this paper is to summarize the current status of percutaneous methods
      for recanalizing peripheral arterial occlusions. Emphasis is placed on the role
      of peripheral intraarterial thrombolysis (PIAT) in the treatment of acute lower
      limb ischemia. Results of three prospective, randomized trials comparing PIAT
      with surgical revascularization are analyzed in the context of the existing,
      largely retrospective literature. The technique and recommendations for the
      application of PIAT are reviewed. Percutaneous aspiration thromboembolectomy, a
      technique that may be used alone or in conjunction with PIAT, is described in
      detail. We conclude with a brief description of various percutaneous mechanical
      thrombectomy devices, which may potentially see application in peripheral
      arterial occlusions.

PMID- 11343185
TI  - Percutaneous interventions for treatment of iliac artery stenoses and occlusions.
AB  - Balloon angioplasty is still the main workhorse for percutaneous interventions in
      the iliac arteries. It is simple to perform, cost-effective, and remarkably safe.
      If an adequate hemodynamic result has been achieved, patency is acceptable. To
      monitor the quality of success, intraarterial pressure monitoring is an important
      tool. Balloon angioplasty may be followed by stent insertion in case of
      insufficient luminal gain after inadequate balloon angioplasty or occurrence of
      significant dissection. Percutaneous treatment of chronic iliac occlusions is
      technically challenging. For chronic occlusions (duration exceeding 3 months),
      balloon angioplasty alone, thrombolysis with subsequent balloon angioplasty, and
      elective stenting or mechanical passage of the occlusion followed by primary
      stent implantation have been described as alternative techniques. In case of in
      stent stenosis, directional atherectomy or balloon dilatation is recommended.
      Stent grafts allow percutaneous exclusion of isolated iliac aneurysms, iatrogenic
      perforation, rupture, and arteriovenous fistulas, but these cases are rare. Some
      authors increasingly favor the use of endoluminal graft systems for treating
      atherosclerotic disease in iliac arteries, but insufficient data are available to
      prove the benefit of stent grafts in patients with atherosclerotic disease.

PMID- 11343187
TI  - Endoluminal treatment of internal carotid artery stenosis.
AB  - Percutaneous transluminal stent-angioplasty of the carotid artery has indications
      that are similar but not identical to those for carotid surgery. Certain clinical
      conditions and morphologic findings, such as myocardial infarction, occlusion of
      the contralateral carotid artery, or tandem stenoses, favor use of the
      endoluminal technique. On the other hand, large clots at the site of stenosis,
      heavily calcified plaques, or elongated, kinked carotid arteries are better
      suited for carotid endarterectomy. Our experiences with angioplasty of more than
      800 carotid stenoses and reports of other groups dealing with carotid angioplasty
      permit a preliminary evaluation of the method. The technical success rates,
      complication rates, and the few known long-term results are more or less equal to
      those of vascular surgery. Therefore further prospectively randomized studies are
      necessary to determine from which procedure the patient with his or her
      individual condition can gain the highest benefit.

PMID- 11343189
TI  - Transjugular intrahepatic portosystemic shunt: present status, comparison with
      endoscopic therapy and shunt surgery, and future prospectives.
AB  - During the 13 years since its introduction into clinical practice, transjugular
      intrahepatic portosystemic shunt (TIPS) has become widely accepted worldwide as a
      percutaneous, interventional procedure for treating complications of portal
      hypertension. An experienced, skillful team, however, is necessary to ensure the
      high technical success of TIPS and to avoid its potential procedural
      complications. Presently, TIPS is used mainly for treatment of acute or recurrent
      hemorrhage from gastroesophageal varices refractory to endoscopic therapy.
      Randomized studies have shown that it is more effective than endoscopic treatment
      for preventing rebleeding; however, it is associated with a higher incidence of
      encephalopathy. Both treatments produce comparable survival rates. TIPS is also
      effective in the treatment of hepatogenic ascites and hydrothorax and hepatorenal
      syndrome. In comparison with surgical shunts, TIPS is a significantly less
      invasive procedure that can be done in poor surgical candidates with advanced
      cirrhosis. The high rate of shunt obstructions seen with TIPS mandates close
      surveillance and maintenance, rendering TIPS a multistage procedure. This is a
      major disadvantage of TIPS compared to surgery. Presently, both TIPS and surgical
      shunts have their place in the treatment of gastroesophageal variceal hemorrhage
      unresponsive to endoscopic therapy. TIPS is most suited for class B and C
      patients, particularly those who are candidates for liver transplantation.
      Surgical shunts should be considered for patients with well preserved liver
      function. Large, randomized controlled studies should be done to compare these
      treatment methods. Animal experimental and early clinical studies using covered
      stents (stent-grafts) are promising for the prevention of shunt obstructions and
      thus converting TIPS from a multistage to a one-stage procedure.

PMID- 11343191
TI  - Percutaneous endoprosthesis for treatment of aortic aneurysms.
AB  - The purpose of this study was to define the clinical utility of stent-grafts for
      endoluminal treatment of infrarenal abdominal aortic aneurysms (AAAs). In a
      prospective study involving three centers, bifurcated stent-grafts for
      endovascular repair of infrarenal AAAs were implanted in 295 patients. Patient
      selection was based on anatomic suitability. For analysis of the initial and
      follow-up results the patients were divided in three subgroups. Group 1 included
      patients treated between August 1994 and April 1996 with use of the original
      stent-graft device; group 2 comprised patients treated between May 1996 and
      December 1997 with the refined stent-graft device, and group 3 comprised patients
      treated with a newly designed bifurcated stent-graft device. In group 1 (n = 111)
      the primary technical success was 82%. The procedure had to be converted to
      surgery in four patients. Endoleaks immediately after the procedure were observed
      in 16 patients. The initial technical success in subgroup 2 (n = 159) was 96%.
      One patient required surgical repair, and five others had immediate perigraft
      flow due to reperfusion via lumbar arteries. For group 3 (n = 28) the primary
      technical success rate was 89%. Endoleaks due to back-bleeding via lumbar
      arteries were demonstrated in three patients. Minor and major complications
      related to the intervention, including two perioperative deaths, were observed in
      24 patients (8%). Serious problems such as distal migration or disconnection of
      the stent-graft were detected during follow-up in five patients. Delayed aortic
      rupture occurred in three patients who survived after successful surgical repair.
      Based on the initial results and a limited follow-up of 35 months, we believe
      endoluminal repair of infrarenal AAA with use of bifurcated endografts may be a
      feasible alternative to conventional surgery, especially for patients at high
      surgical risk. However, at the present time there are major concerns with respect
      to the structural integrity of stent-graft material and the fate of the proximal
      aortic cuff in the long-term time frame.

PMID- 11343193
TI  - Internal stenting in malignant biliary obstruction.
AB  - Internal stenting in inoperable malignant biliary obstruction plays an important
      role in patient management. Surgical bypass may still be undertaken where there
      is also duodenal obstruction, though the need for gastroenterostomy may be
      reduced with the increasing use of metallic stents for the relief of malignant
      gastric outlet obstruction. Stents may be placed endoscopically or
      percutaneously, though in most centers the endoscopic route is usually tried
      first, with the percutaneous route being reserved for endoscopic failures.
      Plastic and self-expanding metallic biliary stents are available, each with its
      own advantages and disadvantages. In general, longer periods of patency are
      observed with metallic stents, though they are more expensive. Plastic stents can
      be changed endoscopically relatively easily when they have blocked, and in
      practice it is common for plastic stents to be inserted via this route for
      initial biliary drainage. If there is prolonged survival thereafter, many workers
      insert a metallic stent in an attempt to reduce the number of interventions
      required. If the percutaneous route is being employed, the histologic diagnosis
      has been confirmed, and the malignancy is inoperable, our practice is to use a
      self-expanding metallic stent, as the delivery system is relatively small and
      subsequent occlusion less likely.

PMID- 11343195
TI  - Percutaneous abscess drainage: update.
AB  - During the approximately 20 years that percutaneous abscess drainage (PAD) has
      been an extant procedure and as the millennium begins, PAD has become, by
      consensus, the treatment of choice for abscesses. Indications for PAD continue to
      expand, and currently almost all abscesses are considered amenable. On occasion,
      PAD is an adjunctive procedure that provides a beneficial temporizing effect for
      the surgeon who eventually must operate for a coexisting problem such as a bowel
      leak. Simple unilocular abscesses are cured almost uniformly by PAD; more
      complicated abscesses, such as those with enteric fistulas (e.g., diverticular
      abscess) or pancreatic abscesses, have cure rates ranging from 65% to 90%.
      Various catheters and insertion techniques have proven effective.
      Ultrasonography, computed tomography, and fluoroscopy are the staple modalities
      that guide PAD. PAD is the prototype interventional radiology procedure,
      providing detection of the abscess by imaging, needling for diagnosis, and
      catheterization for therapy.

PMID- 11343197
TI  - Percutaneous needle biopsy of the lung and its impact on patient management.
AB  - Percutaneous needle biopsy (PNB) of the lung is a commonly performed procedure,
      mainly used for the investigation of solitary pulmonary nodules. Developments in
      imaging, particularly computed tomography (CT), have enable accurate preliminary
      assessment and targeting of lesions. Improvements in needle design ensure the
      provision of diagnostic samples for both cytologic and histologic assessment; and
      the development of immunocytochemistry and immunohistochemistry have allowed
      improved accuracy in diagnosis. A significant improvement in diagnostic accuracy
      for benign lesions has been associated with the use of cutting needles that
      provide cores for histologic diagnosis, in contrast to cytologic analysis from
      fine-needle aspiration. The complications of PNB are well recorded and have not
      changed significantly with the newer imaging techniques and needles. The
      preliminary assessment of solitary pulmonary nodules, and the pretest likelihood
      of malignancy, has improved using contrast-enhanced CT and positron emission
      tomography; the latter modality is increasingly having a major impact on the
      investigation of patients with suspected malignancy. The performance of PNB must
      always be determined on an individual case basis and when the result is likely to
      affect management. The complementary roles of PNB, bronchoscopic biopsy, and
      video-assisted thoracoscopic biopsy continue to evolve.

PMID- 11343199
TI  - New therapy complementary to transcatheter arterial embolization for
      hepatocellular carcinoma.
AB  - A new therapy complementary to transcatheter arterial embolization (TAE) in which
      anticancer agents are percutaneously injected into the tumor under ultrasound
      guidance (percutaneous injection chemotherapy combined with TAE; TAE-PICT) has
      been developed and found to be effective. A total of 68 hepatocellular carcinoma
      (HCC) nodules in 50 patients were treated with TAE-PICT, and the complications
      were evaluated. Among those with solitary HCC nodules < or = 5 cm in diameter, 17
      were treated with TAE-PICT and 24 with only TAE in a prospective comparative
      study. No major complications were seen, and the anticancer drugs could still be
      found in the tumor 3 months after injection. A significantly higher cumulative
      survival rate (p= 0.03961) and significantly higher cumulative recurrence-free
      survival rate (p = 0.00647) were achieved in patients treated with TAE-PICT than
      in those treated with TAE alone.

PMID- 11343202
TI  - Re: Gollackner, B et al: Radical surgical therapy of abdominal cystic hydatid
      disease: factors of recurrence. World J. Surg. 24:717,2000.

PMID- 11343201
TI  - Re: Paolucci, V et al: Tumor seeding following laparoscopy: international survey.
      World J. Surg. 23:989,1999.

PMID- 11343203
TI  - Modification of maternal and congenital cytomegalovirus infection by anti
      glycoprotein b antibody transfer in guinea pigs.
AB  - Prepregnancy human and guinea pig cytomegalovirus immunity reduces rates of
      congenital infection in subsequent pregnancies. Inbred JY-9 strain guinea pigs
      were used to study the role of hyperimmune anti-glycoprotein B (gB) serum in
      modification of congenital infection in early pregnancy. Significantly shorter
      duration of primary maternal viremia and fewer pregnancy losses occurred in
      passively immunized dams, compared with nonimmune dams. Placentas from recipients
      of negative control serum were smaller and had marked mononuclear cell
      infiltrates and focal necrosis and more viral foci than did those from recipients
      of anti-gB hyperimmune serum. Significantly higher intrauterine growth
      retardation occurred in pups of negative control serum recipients than in pups of
      passively immunized dams. Significantly higher proportions of pups and placentas
      from recipients of negative control serum were positive on viral culture than
      from passively immunized dams. Thus, anti-gB passive immunization decreased fetal
      infection and intrauterine growth retardation, shortened maternal viremia, and
      reduced pregnancy losses and placental inflammation and infection.

PMID- 11343204
TI  - Determinants of genital human papillomavirus detection in a US population.
AB  - This study investigated the association of selected demographic and behavioral
      characteristics with the detection of low-risk, high-risk, and uncharacterized
      genital human papillomavirus (HPV) in women attending clinic for routine
      nonreferral gynecologic health care. Cervical specimens obtained from 3863 women
      18-40 years old (mean, 28 years) with no history of high-grade cervical disease
      were analyzed for 38 HPV types. Overall, HPV prevalence was 39.2%. The prevalence
      of high-risk, low-risk, and uncharacterized HPV types was 26.7%, 14.7%, and
      13.0%, respectively. As expected, the characteristics most strongly associated
      with overall HPV detection were age and numbers of lifetime and recent sex
      partners. Low-risk, high-risk, and uncharacterized HPV detection increased with
      increasing numbers of sex partners. There was a decline in high-risk and low-risk
      HPV detection with increasing age but little change in uncharacterized HPV
      detection. These results suggest that the uncharacterized HPV types have a
      different natural history than either low-risk or high-risk HPV types.

PMID- 11343206
TI  - Immune recovery under highly active antiretroviral therapy is associated with
      restoration of lymphocyte proliferation and interferon-gamma production in the
      presence of Toxoplasma gondii antigens.
AB  - The in vitro lymphocyte proliferative response (LPR) and interferon (IFN)-gamma
      production in the presence of Toxoplasma antigen were evaluated in 97 human
      immunodeficiency virus (HIV)-1-infected patients with CD4 cell counts of <100
      cells/microL (group 1), currently >300 cells/microL but previously <100
      cells/microL (group 2), or always >300 cells/microL (group 3) and in 28 non-HIV
      infected blood donors (group 4), all seropositive to Toxoplasma. In group 2, 81%
      of patients had a positive LPR, versus 20% in group 1 (P<10(-3)). IFN-gamma
      production was greater in group 2 than in group 1 (922 vs. 0 Deltapg/mL; P=10(
      4)). Multivariate analysis found a significant association between a positive LPR
      to Toxoplasma antigen and a CD4 count >300 cells/microL (odds ratio [OR], 16.3;
      95% confidence interval [CI], 5.3-50.2) and anti-Toxoplasma IgG titer >150 IU/mL
      (OR, 5; 95% CI, 1.6-15.2). Immune reconstitution under highly active
      antiretroviral therapy was associated with a restoration of immune responses
      against Toxoplasma.

PMID- 11343205
TI  - Frequency and phenotyping of human immunodeficiency virus (HIV)-specific CD8+ T
      cells in HIV-infected children, using major histocompatibility complex class I
      peptide tetramers.
AB  - HLA-A*02 tetramers complexed to human immunodeficiency virus (HIV) Gag SLYNTVATL
      and HIV Pol ILKEPVHGV peptides were used to characterize HLA class I-restricted
      CD8(+) T cells in 41 HIV-infected children. The frequencies and the phenotype of
      specific circulating CD8(+) T cells were determined in whole-blood samples by
      means of cytometric analysis. Background staining of 13 HLA-A*02-negative
      patients showed that the frequency of CD8(+) T cells was <0.01%. Of the 28 HLA
      A*02-positive patients, blood samples from 26 stained positive at least once the
      Gag tetramer (mean CD8(+) T cells, 0.87%; range, 0.1%-3.9%), and blood samples
      from 21 stained positive for the Pol tetramer (mean CD8(+) T cells, 0.59%; range,
      0.1%-5.5%). The tetramer-binding cells were CD28(-), CD45RA(-), CD45RO(+), HLA
      DR(+), and CD69(-) T lymphocytes. HIV-specific CD8(+) T cells can be detected
      easily in peripheral blood of HIV-infected children, using HLA tetramers combined
      with HIV peptides. These cells are memory activated CD28(-)CD8(+) T lymphocytes.

PMID- 11343207
TI  - A human immunodeficiency virus-transgenic mouse model for assessing interventions
      that block microbial-induced proviral expression.
AB  - A human immunodeficiency virus (HIV) type 1-transgenic mouse line (166) that
      previously showed up-regulated expression of viral proteins and infectious
      particles after infection with pathogenic agents was tested as a model for
      screening the in vitro and in vivo efficacy of inhibitors of HIV-1 immune
      activation. Two types of interventions were assessed: use of either the
      immunosuppressive drug prednisolone or an HIV-1 envelope-targeted toxin (sCD4
      PE40). Both agents inhibited lipopolysaccharide-induced p24 expression by
      splenocytes in vitro and, when administered to transgenic mice, suppressed the
      induction of plasma p24, as well as the ex vivo production of p24 and infectious
      virus stimulated by in vivo infection with Mycobacterium avium. Moreover, HIV-1
      mRNA levels in the spleen were greatly reduced in mice treated with either agent.
      Because HIV-1 expression cannot be induced in T lymphocytes from line 166 mice,
      this model may be of particular advantage for testing interventions that target
      virus production by non-T cell virus reservoirs.

PMID- 11343208
TI  - Molecular subtyping of Treponema pallidum in an Arizona County with increasing
      syphilis morbidity: use of specimens from ulcers and blood.
AB  - A molecular-based subtyping system for Treponema pallidum was used during an
      investigation of increasing syphilis in Maricopa County, Arizona. Genital ulcer
      or whole blood specimens from patients with syphilis were assayed by a polymerase
      chain reaction (PCR) amplification of a T. pallidum DNA polymerase I gene.
      Positive specimens were typed on the basis of PCR amplification of 2 variable
      genes. In all, 41 (93%) of 44 of ulcer specimens and 4 (27%) of 15 blood
      specimens yielded typeable T. pallidum DNA. Twenty-four (53%) of 45 specimens
      were subtype 14f; other subtypes identified included 4f, 4i, 5f, 12a, 12f, 14a,
      14d, 14e, and 14i. Only 2 specimens were from epidemiologically linked patients.
      This investigation demonstrates that multiple subtypes of T. pallidum can be
      found in an area with high syphilis morbidity, although 1 subtype (14f) was
      predominant. Four typeable specimens were from blood, a newly identified specimen
      source for subtyping.

PMID- 11343209
TI  - Secretion of the virulence-associated Campylobacter invasion antigens from
      Campylobacter jejuni requires a stimulatory signal.
AB  - Campylobacter jejuni are a common cause of human diarrheal illness. Previous work
      has demonstrated that C. jejuni synthesize a novel set of proteins upon
      coculturing with epithelial cells, some of which are secreted. The secreted
      proteins have been collectively referred to as Campylobacter invasion antigens
      (Cia proteins). Metabolic labeling experiments revealed that Cia protein
      synthesis and secretion are separable and that secretion is the rate-limiting
      step of these processes. Additional work indicated that Cia protein synthesis is
      induced in response to bile salts and various eukaryotic host cell components.
      Host cell components also can induce Cia protein secretion. Culturing C. jejuni
      on plates supplemented with the bile salt deoxycholate retarded the inhibitory
      effect of chloramphenicol on C. jejuni invasion, as judged by the gentamicin
      protection assay. These data suggest that the coordinate expression of the genes
      encoding the Cia proteins is subject to environmental regulation.

PMID- 11343210
TI  - In vivo expression of proinflammatory mediators in the adult heart after
      endotoxin administration: the role of toll-like receptor-4.
AB  - Tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and nitric oxide (NO)
      may play a role in lipopolysaccharide (LPS)-induced cardiac depression. Toll-like
      receptor-4 (TLR-4) mediates the cytokine response to LPS in immune cells. TLR-4
      also is expressed in human and murine myocardial tissue. Therefore, the
      hypothesis that LPS induces proinflammatory cytokines in the heart via TLR-4 was
      tested. C3H/HeJ (TLR-4 deficient) and C3HeB/FeJ mice were studied. LPS induced a
      robust increase in myocardial TNF-alpha and IL-1beta mRNA in C3HeB/FeJ mice. The
      response in C3H/HeJ mice was blunted and delayed. Myocardial TNF-alpha and IL
      1beta protein levels were higher in C3HeB/FeJ mice, as were inducible NO synthase
      protein and NO production. Activation of myocardial NF-kappaB was observed within
      30 min in C3HeB/FeJ mice but not in C3H/HeJ mice. These findings suggest that
      myocardial TLR-4 is involved in signaling cytokine production within the heart
      during endotoxic shock.

PMID- 11343211
TI  - Risk of hospitalization for cardiovascular disease after use of macrolides and
      penicillins: a comparative prospective cohort study.
AB  - Chlamydia pneumoniae has been associated with cardiovascular diseases, and C.
      pneumoniae infection is treatable with macrolides. In this comparative cohort
      study, 634 users of macrolides and 3827 users of penicillins were identified from
      the Danish Health Service Registry of Prescriptions and followed up for an
      average of 6 months. The patients were then linked to the Regional Hospital
      Discharge Registry to assess the outcome of hospitalization for cardiovascular
      disease. In the first 3 months, the relative risk (RR) of admission for a
      cardiovascular disease was 0.48 (95% confidence interval, 0.27-0.88) in users of
      macrolides compared with users of penicillins. No difference was seen after 3
      months. Interaction analyses indicated that the lower risk seen in users of
      macrolides could be more pronounced in patients without versus those with a
      previous cardiovascular disease (RR, 0.39 vs. 0.52), in patients >or=60 versus
      <60 years old (RR, 0.39 vs. 0.64), and in men versus women (RR, 0.35 vs. 0.67).

PMID- 11343212
TI  - Murine Lyme disease: no evidence for active immune down-regulation in resolving
      or subclinical infection.
AB  - Macrophages in vitro rapidly ingest and kill Borrelia burgdorferi, yet some
      spirochetes in vivo may survive in the host and lead to complications of Lyme
      disease. One strategy for such survival may be the down-regulation of the immune
      system. To test this, we evaluated the degree of macrophage activation in a site
      of active disease-the heart-by examining cytokine expression in murine
      macrophages from control and B. burgdorferi-infected animals. Using double-label
      immunofluorescent staining in situ, we showed that infiltrating macrophages in
      infected hearts produce interleukin (IL)-1. By semiquantitative reverse
      transcription-polymerase chain reaction analysis, increased levels of mRNA were
      measured for the proinflammatory cytokines IL-1, tumor necrosis factor-alpha, and
      IL-12 during peak and resolving disease. No increases in the anti-inflammatory
      cytokines IL-10 and transforming growth factor-beta were detected. In an infected
      site without active disease--the peritoneal cavity--no increases in levels of
      proinflammatory or anti-inflammatory cytokines were detected in local
      macrophages. Thus, there is no evidence of pressure toward the down-regulation of
      inflammatory activity in the regions tested.

PMID- 11343213
TI  - Polar production of interleukin-8 by mesothelial cells promotes the
      transmesothelial migration of neutrophils: role of intercellular adhesion
      molecule-1.
AB  - Migration of polymorphonuclear neutrophils (PMNL) from the vascular compartment
      into the pleural space occurs rapidly during the development of parapneumonic
      effusions. This study investigated the polarized secretion of interleukin (IL)-8
      in activated pleural mesothelial cells (PMC) and the migration of PMNL across
      resting, activated PMC monolayers. Results show that PMC produce IL-8 in a polar
      manner. When PMC were stimulated with Staphylococcus aureus or IL-1beta at the
      basal or at the apical surface, significantly (P< .05) more IL-8 was released
      toward the apical surface. This polarized production of IL-8 was confirmed by in
      situ hybridization. PMNL migration was higher from the basilar to apical than
      from the apical to basilar surface of PMC. Neutralizing antibodies against IL-8
      and intercellular adhesion molecule (ICAM)-1 significantly (P< .001) blocked PMNL
      migration across activated monolayers. Thus, during pleural inflammation, PMC
      regulate the influx of PMNL into the pleural space by polar production of IL-8
      and expression of ICAM-1.

PMID- 11343214
TI  - Combined interleukin-12 and topical chemotherapy for established Leishmaniasis
      drastically reduces tissue parasitism and relapses in susceptible mice.
AB  - The efficacy of the association of paromomycin sulfate (PA) with recombinant (r)
      interleukin (IL)-12 was investigated by topical treatment of BALB/c mice infected
      with Leishmania major that displayed fully developed cutaneous lesions. Although
      healing was observed in PA-treated groups, lesions recurred in 100% of these
      animals 70 days after treatment. In contrast, lesions were absent in a high
      proportion of PA- and rIL-12-treated mice 120 days after treatment. The PA/rIL-12
      treated mice had a switch in cytokine response, from high IL-4 and low interferon
      (IFN)-gamma levels to low IL-4 and high IFN-gamma levels, and reductions in
      parasite load, dissemination of parasites, and inflammation. Thus, the
      association of rIL-12 to topical chemotherapy for leishmaniasis may be an
      important strategy for increasing cure rates and decreasing the incidence of
      relapse.

PMID- 11343215
TI  - Evidence for different mechanisms of chloroquine resistance in 2 Plasmodium
      species that cause human malaria.
AB  - Chloroquine (CQ)-resistant Plasmodium vivax malaria was first reported 12 years
      ago, nearly 30 years after the recognition of CQ-resistant P. falciparum. Loss of
      CQ efficacy now poses a severe problem for the prevention and treatment of both
      diseases. Mutations in a digestive vacuole protein encoded by a 13-exon gene,
      pfcrt, were shown recently to have a central role in the CQ resistance (CQR) of
      P. falciparum. Whether mutations in pfcrt orthologues of other Plasmodium species
      are involved in CQR remains an open question. This report describes pfcrt
      homologues from P. vivax, P. knowlesi, P. berghei, and Dictyostelium discoideum.
      Synteny between the P. falciparum and P. vivax genes is demonstrated. However, a
      survey of patient isolates and monkey-adapted lines has shown no association
      between in vivo CQR and codon mutations in the P. vivax gene. This is evidence
      that the molecular events underlying P. vivax CQR differ from those in P.
      falciparum.

PMID- 11343216
TI  - Early human infection with Onchocerca volvulus is associated with an enhanced
      parasite-specific cellular immune response.
AB  - The immune response after early exposure to or infection with Onchocerca volvulus
      was investigated in an autochthonous focus caused by the migration of infected
      persons to a previously unaffected area in Ecuador. Peripheral blood mononuclear
      cell (PBMC) proliferative and cytokine responses (interferon [IFN]-gamma and
      interleukin [IL]-5) to filarial antigens were measured in 14 subjects with
      serologic evidence of exposure and in 7 subjects with evidence of dermal
      microfilarial DNA and were compared with responses in 43 subjects with chronic O.
      volvulus infections. PBMC proliferative and cytokine responses (IFN-gamma and IL
      5) to parasite antigens were elevated in the early exposure/infection group,
      compared with those in the chronic infection group. Addition of an IL-10
      neutralizing antibody to filaria antigen-stimulated cultures resulted in
      significantly elevated proliferative responses in the chronic infection group.
      The findings suggest that early exposure and early parasite patency are
      associated with a vigorous cellular response, but, as infections become chronic,
      the cellular response becomes down-regulated, partly through an IL-10-dependent
      mechanism.

PMID- 11343217
TI  - Quantitation of BK virus load in serum for the diagnosis of BK virus-associated
      nephropathy in renal transplant recipients.
AB  - BK virus-associated nephropathy is an increasingly recognized cause of graft
      dysfunction among kidney transplant recipients, and definitive diagnosis requires
      renal biopsy. By using a newly developed, quantitative, real-time polymerase
      chain reaction (PCR) assay for BK virus DNA, a retrospective analysis was done of
      sequential serum samples (n=28) from 4 transplant recipients with
      histopathologically documented BK virus nephropathy and from samples (n=76) from
      16 transplant recipient control patients. BK virus DNA was detected in serum
      samples from all 4 case patients versus 0 of 16 control patients (P< .0001,
      Fisher's exact test) at a median of 32 weeks (range, 17-61 weeks) before the
      diagnosis of BK virus nephropathy. BK virus load decreased in 3 of 3 patients
      after the reduction of immunosuppression and/or nephrectomy. It is concluded that
      quantitative PCR for BK virus DNA in serum is useful both for identifying
      transplant recipients at risk for BK virus nephropathy and for monitoring the
      response to therapy.

PMID- 11343218
TI  - Correlates of change in cytomegalovirus viremia in patients with advanced human
      immunodeficiency virus infection who require transfusion.
AB  - The Viral Activation Transfusion Study compared leukocyte-reduced to unfiltered
      red blood cell transfusions in human immunodeficiency virus (HIV)- and
      cytomegalovirus (CMV)-coinfected patients. Relationships between serially
      measured plasma CMV load and clinical and laboratory outcomes over a median of 12
      months were examined in 511 subjects. At baseline, subjects had a median of 15
      CD4(+) cells/mm(3), 25% had CMV disease, and 21.5% were viremic. No relationship
      was found between changes in CMV viremia and changes in HIV RNA. Increased CMV
      viremia was associated with a concomitant fall in Karnofsky score. Highly active
      antiretroviral therapy (HAART) led to a decrease in CMV viremia after a 90-day
      delay. After adjustment for HIV load and CD4(+) cell count, CMV viremia remained
      associated with an increased risk of CMV disease (relative hazard, 5.78). In late
      stage HIV-infected patients, CMV viremia was associated with lower functional
      status and increased risk of CMV disease. HAART suppressed CMV viremia only after
      a delay of several months.

PMID- 11343219
TI  - RANTES production from CD4+ lymphocytes correlates with host genotype and rates
      of human immunodeficiency virus type 1 disease progression.
AB  - Several chemokine and chemokine receptor parameters were measured in peripheral
      blood mononuclear cells obtained from patients before they became infected with
      human immunodeficiency virus type 1 (HIV-1). After HIV-1 infection, the
      parameters were compared with plasma HIV-1 RNA levels and with rates of CD4(+)
      lymphocyte decline. Patients who were heterozygous for the Delta32CCR5 allele had
      significantly higher levels of RANTES production from their CD4(+) lymphocytes
      than did patients who did not carry the Delta32CCR5 allele (P=.01). Higher RANTES
      production levels from ex vivo-activated CD4(+)-enriched lymphocytes, but not
      CD8(+) lymphocytes, correlated with lower plasma HIV-1 RNA levels 9-12 months
      after infection (P= .01) and with slower rates of CD4(+) lymphocyte decline (P=
      .002). CCR5 expression levels on ex vivo-activated CD4(+) lymphocytes did not
      correlate with markers of disease progression. These results further support the
      hypothesis that chemokine production levels are associated with HIV-1 replication
      in vivo.

PMID- 11343220
TI  - Human immunodeficiency virus type 1-infected persons with residual disease and
      virus reservoirs on suppressive highly active antiretroviral therapy can be
      stratified into relevant virologic and immunologic subgroups.
AB  - A significant percentage of human immunodeficiency virus type 1 (HIV-1)-infected
      persons treated with highly active antiretroviral therapy (HAART) will develop
      plasma HIV-1-specific virion RNA levels <50 copies/mL. HIV-1-infected persons
      receiving virally suppressive HAART were studied with a viral outgrowth assay of
      the patients' peripheral blood mononuclear cells (PBMC), and a quantitative
      polymerase chain reaction assay was used to analyze HIV-1 2-long terminal repeat
      (2-LTR) circular DNA in PBMC, which indicates new HIV-1 infections of cells in
      vivo. Viral outgrowth in vitro correlated inversely with the level of peripheral
      blood CD4(+) T lymphocytes. Detection and quantitation of 2-LTR circular DNA
      correlated strongly with viral outgrowth patterns and inversely with CD4(+) T
      lymphocyte counts. Relevant subgroups of HIV-1-infected subjects on suppressive
      HAART with residual viral disease and reservoirs can now be stratified.

PMID- 11343222
TI  - Phylogenetic classification of serotype III group B streptococci on the basis of
      hylB gene analysis and DNA sequences specific to restriction digest pattern type
      III-3.
AB  - Previous work divided serotype III group B streptococci (GBS) into 3 major
      phylogenetic lineages (III-1, III-2, and III-3) on the basis of bacterial DNA
      restriction digest patterns (RDPs). Most neonatal invasive disease was caused by
      III-3 strains, which implies that III-3 strains are more virulent than III-2 or
      III-1 strains. In the current studies, all RDP III-3 and III-1 strains expressed
      hyaluronate lysase activity; however, all III-2 strains lack hyaluronate lysase
      activity, because the gene that encodes hyaluronate lysase, hylB, is inactivated
      by IS1548. Subtractive hybridization was used to identify 9 short DNA sequences
      that are present in all the III-3 strains but not in any of the III-2 or III-1
      strains. With 1 exception, these III-3-specific sequences were not detected in
      nonserotype III GBS. These data further validate the RDP-based subclassification
      of GBS and suggest that lineage-specific genes will be identified, which account
      for the differences in virulence among the lineages.

PMID- 11343221
TI  - Vertical transmission of multidrug-resistant human immunodeficiency virus type 1
      (HIV-1) and continued evolution of drug resistance in an HIV-1-infected infant.
AB  - To confirm the vertical transmission of multidrug-resistant (MDR) human
      immunodeficiency virus type 1 (HIV-1) and to assess its impact on further
      evolution of drug-resistant virus in an infant, proviral DNA amplified from
      infected peripheral blood mononuclear cell cultures was sequenced to identify
      reverse transcriptase (RT) and protease (PR) mutations. The infant had proviral
      DNA with evidence of RT mutations (M41L, L74V, and T215Y) and 3 PR substitutions
      (K20R, M36I, and V82A). After delivery, the mother's proviral DNA had the same
      substitutions. Phylogenetic analyses of these HIV-1 RT and PR sequences indicated
      epidemiological linkage. Plasma drug susceptibility was determined by using a
      recombinant virus assay. Plasma HIV-1 obtained after the infant's birth
      demonstrated reduced susceptibility to zidovudine and ritonavir. Thus, vertical
      transmission of MDR HIV-1 was demonstrated in the setting of detectable maternal
      plasma viremia. Further accumulation of broad MDR in the infant's virus to 3
      antiretroviral classes occurred, despite postnatal therapy.

PMID- 11343223
TI  - Diphtheria antitoxin levels among children primed with a diphtheria and tetanus
      toxoids and acellular pertussis vaccine lot with a subpotent diphtheria toxoid
      component.
AB  - One lot of a nationally distributed diphtheria and tetanus toxoids and acellular
      pertussis (DTaP) vaccine was recalled in January 1999 because of a subpotent
      diphtheria toxoid component. To evaluate vaccine immunogenicity, children who had
      received the recalled lot for at least 2 of the 3 doses of their primary series
      were identified. Diphtheria antitoxin (DAT) levels were then prospectively
      assessed before and after dose 4 of (fully potent) DTaP vaccine. Of the 105
      children evaluated, 84% had prevaccination DAT levels <0.10 IU/mL, which is the
      level generally accepted as protective. DAT levels rose a mean of 92-fold after
      dose 4; 100% of subjects had DAT levels >or=0.10 IU/mL, and 69% had DAT levels
      >or=1.0 IU/mL. These results indicate that diphtheria potency testing can
      identify vaccine that is less immunogenic when administered during the primary
      series. The booster response to dose 4, although reduced, was sufficient to
      confer adequate protection in the interval before receipt of the fifth dose of
      DTaP.

PMID- 11343226
TI  - Sickle cell hepatopathy.

PMID- 11343224
TI  - Antimicrobial-resistant bacterial diarrhea in rural western Kenya.
AB  - Bacterial diarrheal diseases cause substantial morbidity and mortality in sub
      Saharan Africa, but data on the epidemiology and antimicrobial susceptibility
      patterns of enteric bacterial pathogens are limited. Between May 1997 and April
      1998, a clinic-based surveillance for diarrheal disease was conducted in Asembo,
      a rural area in western Kenya. In total, 729 diarrheal specimens were collected,
      and 244 (33%) yielded >or=1 bacterial pathogen, as determined by standard culture
      techniques; 107 (44%) Shigella isolates, 73 (30%) Campylobacter isolates, 45
      (18%) Vibrio cholerae O1 isolates, and 33 (14%) Salmonella isolates were
      identified. Shigella dysenteriae type 1 accounted for 22 (21%) of the Shigella
      isolates. Among 112 patients empirically treated with an antimicrobial agent and
      whose stool specimens yielded isolates on which resistance testing was done, 57
      (51%) had isolates that were not susceptible to their antimicrobial treatment.
      Empiric treatment strategies for diarrheal disease in western Kenya need to be
      reevaluated, to improve clinical care.

PMID- 11343227
TI  - Positron emission tomography with [(18)F]fluoro-2-deoxy-D-glucose for diagnosis
      and staging of bile duct cancer.
AB  - Malignant tumors with high glucose metabolic rates accumulate [18F]
      fluorodeoxyglucose (FDG), a positron emitting tracer. The aim of this study was
      to evaluate FDG positron emission tomography (PET) for detection and staging of
      human cholangiocarcinoma (CC). Patients with adenocarcinoma of the biliary tree
      (n = 26), with benign lesions of the bile ducts (n = 8), and 20 control patients
      underwent FDG-PET (370 MBq [18F]-FDG, Siemens ECAT EXACT HR(+)). In a blinded
      fashion, 4 independent experts evaluated the PET scans visually and
      semiquantitatively using the standardized uptake value and a tumor/non-tumor
      ratio. All adenocarcinomas and benign lesions (sclerosing cholangitis, bile duct
      adenoma, Caroli's disease) were histologically proven and imaged by magnetic
      resonance imaging and endoscopic retrograde cholangioscopy. True-positive PET
      scans were obtained in 24 of 26 CC and false-negative scans in the other 2
      (sensitivity 92.3%). The PET scan was true-negative in 18 of 20 controls and in
      all 8 benign biliary lesions (specificity 92.9%). Visual and semiquantitative
      evaluation using tumor/non-tumor ratios were equally accurate (accuracy 92.6%)
      whereas evaluation by standardized uptake value revealed lower accuracy (P <.05).
      Regional or hepatoduodenal lymph node metastases were detected with PET in only 2
      of 15 cases whereas distant metastases (peritoneal carcinomatosis, pulmonary
      metastases) were diagnosed in 7 of 10 cases. In conclusion, PET is highly
      sensitive and specific for the detection and localization of CC. It can be
      helpful for diagnosis of distant metastases but is not suitable for detection of
      regional lymph node metastases.

PMID- 11343228
TI  - Human REG I gene is up-regulated in intrahepatic cholangiocarcinoma and its
      precursor lesions.
AB  - The Reg I gene (regenerating gene) and its product (Reg protein) are a
      regenerating and/or proliferating factor(s) of pancreatic islet cells. The
      ectopic expression of REG Ialpha was shown in colorectal carcinomas, suggesting
      that REG Ialpha is related to their carcinogenesis. In this study, we examined
      the expression of REG I in intrahepatic cholangiocarcinoma (ICC) and its
      precursor lesion (biliary dysplasia). By polymerase chain reaction and in situ
      hybridization (ISH) studies using a total of 16 fresh liver specimens, REG Ialpha
      mRNA was demonstrated in 6 of 11 (55%) ICC cases, but in 0 of 5 (0%) normal
      livers. Immunohistochemistry for REG I protein was performed in 100 formalin
      fixed, paraffin-embedded sections obtained from the 18 cases of ICC alone, 45
      hepatolithiasis with ICC (n = 19) or biliary dysplasia (n = 26), 21
      hepatolithiasis alone (all with hyperplasia), and 16 normal livers. In ICC, the
      expression of REG I protein was significantly dependent on the histologic
      differentiation; 12 of 13 (92%) cases in papillary and well-differentiated, 6 of
      16 (38%) cases in moderately differentiated, and 0 of 8 (0%) cases in poorly
      differentiated types. Moreover, in the lesions of hyperplasia, low-grade
      dysplasia, and high-grade dysplasia in hepatolithiasis, REG I protein was
      expressed in 4 of 21 (19%), 7 of 12 (58%), and 13 of 14 (93%) cases,
      respectively. In normal liver, intrahepatic bile ducts were constantly negative
      for REG I protein. These findings suggest that neoexpression of REG I is a good
      marker for biliary mucosa at risk for development of ICC, and also that REG I
      plays a role in the early stages of biliary carcinogenesis, probably via a cell
      proliferative effect.

PMID- 11343229
TI  - Contact sensitization pretransplantation predicts acute hepatic allograft
      rejection.
AB  - The loss of hepatic allografts to the rejection processes is now relatively rare,
      and the reduction of adverse effects related to immunosuppressive therapy is
      becoming more important as patients survive longer after transplantation. We
      therefore investigated the response to a contact neoantigen before liver
      transplantation as a predictor of acute rejection after transplantation. Forty
      one patients with chronic liver disease were sensitized with 0.1%
      diphenylcyclopropenone while on the waiting list for orthotopic liver
      transplantation. Fourteen days later an elicitation reaction was performed with 5
      different concentrations of diphenylcyclopropenone. Nineteen responded to
      diphenylcyclopropenone (score range, 1-9). Twenty-two patients had no response.
      Three patients died before transplantation (all nonresponders). Twelve (63%) of
      19 responders had treatment for acute rejection compared with 1 of 19
      nonresponders (P < .0001). In addition univariate analysis revealed recipient
      age, donor age, Child-Pugh class, and immunosuppressive agent to be associated
      with acute rejection. On multivariate analysis only skin test response was a
      significant predictor of acute rejection (P = .02). All nonresponders had no or
      only mild rejection on biopsy, but 12 of 19 responders had moderate or severe
      acute rejection on biopsy. All patients requiring additional therapy to a single
      course of corticosteroids for acute rejection had skin test scores greater than
      1. We concluded that patients who do not respond to diphenylcyclopropenone
      sensitization before transplantation develop at most mild acute rejection and
      that skin test scores identify patients with troublesome rejection. Evaluation of
      skin test responses to a contact neoantigen may facilitate tailoring of
      immunosuppressive therapy.

PMID- 11343230
TI  - Autoimmune regulator AIRE: evidence for genetic differences between autoimmune
      hepatitis and hepatitis as part of the autoimmune polyglandular syndrome type 1.
AB  - The mechanisms driving the immune-mediated destruction of hepatic tissues in
      autoimmune hepatitis (AIH) are unknown. Recently the autoimmune regulator (AIRE),
      a gene associated with the development of the autoimmune polyglandular syndrome
      type 1 (APS-1), was cloned. About 15% to 20% of APS-1 patients develop hepatitis.
      However, the role of AIRE mutations in AIH, primary sclerosing cholangitis (PSC),
      and primary biliary cirrhosis (PBC) is not known. To address this issue patients
      with AIH (n = 94), PSC (n = 60), and PBC (n = 30) were analyzed for the presence
      of mutations in exons 6, 8, and 10 of AIRE by single stranded conformation
      polymorphism and sequence analysis. Autoantibody patterns of patients with
      defects in AIRE were analyzed by indirect immunofluorescence, enzyme-linked
      immunosorbent assay and Western blot. Heterozygous mutations of AIRE were
      identified in 3 patients: a patient with PBC and a patient with AIH type 1
      carried a R257X mutation, and a patient with AIH type 2, diabetes mellitus type 1
      (IDDM), thyroid disease, and atrophic gastritis carried a G305S mutation in the
      first PHD ring finger domain of the AIRE protein. None of the 3 patients with a
      defective AIRE allele showed autoantibodies, which are known to associate with
      APS-1. These findings show a differential genetic association of autoimmune liver
      diseases and hepatitis in APS-1. The subgroup of patients with heterozygous
      mutations in AIRE does not represent patients with an incomplete APS-1 syndrome.
      However, the Aire gene defect showed that genes involved in the induction of
      immunologic tolerance provide candidates for etiologic factors in autoimmune
      liver diseases.

PMID- 11343231
TI  - Characterization of autoantibodies against uridine-diphosphate
      glucuronosyltransferase in patients with inflammatory liver diseases.
AB  - Uridine diphosphate glucuronosyltransferase (UGT) was identified as an antigenic
      target in a subgroup of liver-kidney microsomal autoantibodies and was termed LKM
      3. To evaluate the nature of LKM-3 antibodies, we screened sera from 80 untreated
      patients with autoimmune hepatitis (AIH) type 1 and 2, primary biliary cirrhosis
      (PBC), AIH/PBC, hepatitis C virus (HCV) infection, and 12 healthy individuals
      (controls) against 7 recombinant human UGT isoenzymes (UGT1A1, UGT1A4, UGT1A6,
      UGT1A7, UGT1A9, UGT1A10, and UGT2B7). Autoantibodies reacting against various UGT
      isoenzymes were observed in sera from 3 of 18 AIH type 2 and 1 of 27 of the HCV
      patients. The anti-UGT-positive sera from AIH type 2 patients revealed the
      strongest immunoreactivity against UGT1A1, the main UGT-isoform involved in the
      bilirubin glucuronidation. Additionally, these sera were able to block UGT
      mediated substrate glucuronidation in vitro. The prevalence for UGT1A1 was shown
      by 2 independent techniques: (1) UGT1A1 was identified as the main antigen by
      Western blotting. Preabsorption of sera with UGT1A1 prevented reaction against
      all tested UGT-isoforms. (2) In vitro immunoinhibition experiments showed that
      glucuronidation of the anticancer drug flavopiridol by UGT1A1 was more strongly
      inhibited than its UGT1A9-mediated biotransformation. In contrast, the serum from
      the HCV-patient reacted predominately with UGT1A6, and moreover, the
      immunoreactivity pattern was different from that of the AIH group. To summarize,
      we show the subtype preference of antibodies against UGT1A1 in a subgroup of AIH
      type 2 patients. These autoantibodies inhibit UGT-mediated glucuronidation in
      vitro, but it is unlikely that anti-UGT antibodies will have a marked effect on
      the patients capacity for drug biotransformation, as serum bilirubin levels in
      patients remained within the normal range.

PMID- 11343232
TI  - A prospective, randomized trial of butyl cyanoacrylate injection versus band
      ligation in the management of bleeding gastric varices.
AB  - Gastric variceal bleeding is a catastrophic event. Both cyanoacrylate injection
      and banding ligation have been proven to be effective in the management of
      bleeding gastric varices. This study was performed to compare the efficacy and
      complications of both the modalities. Cirrhotic patients with a history of
      gastric variceal bleeding were randomized to 2 groups. The group receiving
      endoscopic obturation (group A) comprised 31 patients and the group receiving
      band ligation (group B) comprised 29 patients. Butyl cyanoacrylate and pneumatic
      driven ligator were applied, respectively. Treatment was repeated regularly until
      obliteration of gastric varices. Active bleeding occurred in 15 patients in group
      A and 11 patients in group B. Initial hemostatic rate (defined as no bleeding for
      72 hours after treatment) was 87% in group A and 45% in group B (P = .03). The
      sessions required to achieve variceal obliteration and obliteration rates were
      similar in both the groups. However, rebleeding rates were significantly higher
      in group B (54%) than group A (31%) (P = .0005). Treatment-induced ulcer bleeding
      occurred in 2 patients (7%) in group A and 8 patients (28%) in group B (P = .03).
      The amount of blood transfusions required were also higher in group B than group
      A (4.2 +/- 1.3 vs. 2.6 +/- 0.9 units, respectively) (P < .01). Nine patients of
      group A and 14 patients of group B died (P = .05). In conclusion, endoscopic
      obturation using cyanoacrylate proved more effective and safer than band ligation
      in the management of bleeding gastric varices.

PMID- 11343233
TI  - MAdCAM-1 expressed in chronic inflammatory liver disease supports mucosal
      lymphocyte adhesion to hepatic endothelium (MAdCAM-1 in chronic inflammatory
      liver disease).
AB  - Mucosal addressin cell adhesion molecule (MAdCAM-1) plays a pivotal role in T
      lymphocyte homing to the gut. Given the strong association between the autoimmune
      liver diseases primary sclerosing cholangitis and autoimmune hepatitis and
      inflammatory bowel disease, we investigated the role of MAdCAM-1 in recruiting
      mucosal lymphocytes to the liver. MAdCAM-1 was strongly expressed on inflamed
      portal vein/sinusoidal endothelium in autoimmune mediated liver disease. In
      modified Stamper-Woodruff assays, MAdCAM-1 on hepatic vessels supported adhesion
      of alpha4beta7+ lymphocytes (i.e., gut-derived T cells) from patients with
      inflammatory bowel disease and primary sclerosing cholangitis. This adhesion was
      inhibited by pretreatment with blocking antibodies to MAdCAM-1, alpha4beta7, or
      the integrin alpha4 chain indicating that MAdCAM-1 in inflamed liver is
      functionally active. Circulating lymphocytes from patients with primary
      sclerosing cholangitis showed rolling adhesion on MAdCAM-1 transfectants in a
      flow-based adhesion assay that could be blocked by anti-MAdCAM-1 or anti
      alpha4beta7 mAbs. These findings indicate that, under certain circumstances,
      vessels in the human liver support adhesion of alpha4beta7+ mucosal lymphocytes
      via binding to aberrantly expressed MAdCAM-1 on liver endothelium. This provides
      a mechanism to explain the hepatic recruitment of mucosal lymphocytes in
      inflammatory liver disease complicating inflammatory bowel disease.

PMID- 11343234
TI  - Living donor liver transplantation for early hepatocellular carcinoma: A life
      expectancy and cost-effectiveness perspective.
AB  - Cadaveric liver transplantation (CLT) is an excellent treatment for early
      hepatocellular carcinoma (HCC). Its use, however, is limited by the shortage of
      grafts, with up to 30% of patients developing contraindications to the procedure
      while waiting for a donor. Living donor liver transplantation (LDLT) has emerged
      as an alternative to overcome this limitation. We compared the consequences of
      LDLT versus CLT using a Markov model balancing the gains and losses in life
      expectancy among donors and recipients. For a 60-year-old recipient with a 70% 5
      year survival after transplantation, a 4% monthly drop-out rate, and a donor with
      1% mortality, LDLT became more effective than CLT after 3.5 months on the waiting
      list. These results varied with the probability of developing contraindications
      to transplantation, the survival after transplantation, and the donor's
      mortality. For a 12-month delay saved on the waiting list, the gain in survival
      provided by LDLT compared with CLT ranged between 0 and 2.8 life years depending
      on survival after transplantation, time spent on the waiting list, and drop-out
      rate. LDLT was cost-effective (less than $50,000 per quality-adjusted life year
      saved) in all scenarios of waiting lists exceeding 7 months, and this figure
      ranged from 2 to 16 months when varying the drop-out rate. LDLT for early HCC
      offered substantial gains in life expectancy with acceptable cost-effectiveness
      ratios when the waiting list exceeds 7 months. The gain in life expectancy and
      the cost-effectiveness of LDLT were more dependent on the drop-out rate and the
      outcome after transplantation than on donor's mortality.

PMID- 11343235
TI  - Vascular invasion and histopathologic grading determine outcome after liver
      transplantation for hepatocellular carcinoma in cirrhosis.
AB  - Selection of patients suffering from hepatocellular carcinoma (HCC) in cirrhosis
      for liver transplantation follows limits of number and diameter of tumor nodules.
      It has not been investigated whether there is a correlation of these parameters
      with vascular invasion. From 1989 to 2000, 1,188 liver transplantations were
      performed in 1,087 patients, including 120 patients (11%) with an HCC in
      cirrhosis. Selection criteria were a maximal diameter of up to 5 cm if the tumor
      appeared to be uninodular or of up to 3 cm in the case of 2 or 3 nodules. The
      postoperative mortality rate was 1.7%. One-, 5-, and 10-year survival was 90%,
      71%, and 60%, respectively. In 940 transplantation patients without an HCC, these
      rates were 93%, 87%, and 83% (P < .0001). Vascular invasion and histopathologic
      grading were identified as prognostic parameters by multivariate analysis. In a
      logistic regression analysis, histopathologic grading and maximal diameter showed
      a significant correlation with a vascular invasion. Analyzing tumors larger than
      5 cm, i.e., tumors not fulfilling the selection criteria as a result of
      diagnostic inaccuracy or progression thereafter, the rates of vascular invasion
      were significantly (P < .01) lower in patients suffering from well-differentiated
      tumors (25%) when compared with moderately and poorly differentiated tumors
      (100%). Liver transplantation is a safe and effective long-term treatment for
      small HCC in cirrhosis. Tumor diameter and number of nodules in correlation with
      the histopathologic grading were predictive of a vascular invasion only in HCC
      larger than 5 cm.

PMID- 11343236
TI  - Involvement of p21(WAF1/Cip1), p27(Kip1), and p18(INK4c) in troglitazone-induced
      cell-cycle arrest in human hepatoma cell lines.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) regulates cell
      growth and differentiation. Recent evidence has suggested that PPARgamma ligands
      had anti-tumor effects through inhibiting cell growth and inducing cell
      differentiation in several types of malignant neoplasm. In the present study, we
      investigated: 1) the expression of PPARgamma in both human hepatoma cell lines
      and 5 resected human hepatocellular carcinoma (HCC) tissues; 2) the growth
      inhibitory effect of troglitazone, a PPARgamma ligand, on those hepatoma cells;
      and 3) the molecular mechanisms of troglitazone-induced cell-cycle arrest. Five
      hepatoma cell lines, HLF, HuH-7, HAK-1A, HAK-1B, and HAK-5, were used. The mRNA
      expression levels of PPARgamma, p21(WAF1/Cip1), and p27(Kip1) were determined by
      real-time quantitative reverse transcription-polymerase chain reaction. The
      expression of cell cycle-regulating proteins, such as p21, p27, p18(INK4c),
      cyclin E, and pRb, was examined using Western blotting. PPARgamma was
      constitutively expressed in all the cell lines and the HCC tissues used in this
      study. A cytostatic effect of troglitazone was found in those cell lines, and
      this inhibition of cell growth was dosage-dependent. G0/G1 arrest was apparently
      demonstrated in flow cytometric analysis in HLF, HAK-1A, HAK-1B, and HAK-5, all
      of which showed an increased expression of p21 protein. However, HuH-7, lacking
      p21 protein expression, did not demonstrate clear arrest in the cell-cycle
      analysis. HLF, which was deficient in the protein product of the retinoblastoma
      tumor-suppressor gene (pRb), responded most profoundly to troglitazone, showing
      an increased expression in not only p21, but also in p27 and in p18. These
      findings suggested that p21, p27, and p18 might be involved in troglitazone
      induced cell-cycle arrest in human hepatoma cells.

PMID- 11343238
TI  - Frequent loss of heterozygosity at the Hcr1 (hepatocarcinogenesis resistance)
      locus on chromosome 10 in primary hepatocellular carcinomas from LFF1 rat strain.
AB  - Hepatocarcinogenesis sensitivity (Hcs1, 2) and resistance (Hcr1-3) loci have been
      identified by linkage analysis on rat chromosomes 7 and 1, and 10, 4, and 8,
      respectively. Cytogenetic studies documented deletions on chromosomes 3 and 6 of
      neoplastic rat hepatocytes. Hepatocellular carcinomas (HCCs) were produced in F1
      hybrid rats between Long-Evans (LE) and Fisher 344 (F344) rats. Scanning of the
      above chromosomes for loss of heterozygosity (LOH) showed allelic imbalance (AI)
      at multiple regions on chromosomes 6, 7, and 10q. Detailed deletion mapping of
      chromosome 10 localized a putative suppressor Hcr1 gene to within a 3.2-cM
      interval flanked by D10Rat51 and D10Rat121. Two other distinct regions with
      frequent AIs were found inside the Hcr1 locus, at marker loci including DNaseI
      and Mrp genes, and in a segment including 4 consecutive markers (D10Rat64,
      D10Rat182, D10Rat113, D10Rat216). In 40% of HCCs, AI was seen at the p53 locus.
      AI on chromosome 7 occurred at the Hcs1 locus, where is located c-myc, which is
      amplified in HCCs, suggesting allelic gain. Most AIs occurred in
      poorly/moderately differentiated carcinomas, and a few events were seen in well
      differentiated tumors on chromosomes 7 and 10. These data suggest that alteration
      of a cluster of oncosuppressor genes on 10q is important for HCC progression. The
      existence of AI on segments of rat chromosomes 6, 7, and 10, syntenic to
      chromosomal segments of human HCCs where chromosomal gains or deletions occur,
      suggests a commonality of some molecular events in the pathogenesis of HCCs in
      rats and humans. Our map provides information toward cloning putative
      oncosuppressor genes associated with this carcinoma.

PMID- 11343237
TI  - Changes in WNT/beta-catenin pathway during regulated growth in rat liver
      regeneration.
AB  - The wnt/beta-catenin pathway is important during embryogenesis and
      carcinogenesis. beta-Catenin interaction with E-cadherin has been shown to be
      crucial in cell-cell adhesion. We report novel findings in the wnt pathway during
      rat liver regeneration after 70% partial hepatectomy using Western blot analyses,
      immunoprecipitation studies, and immunofluorescence. We found wnt-1 and beta
      catenin proteins to be predominantly localized in hepatocytes. Immediately
      following partial hepatectomy, we observed an initial increase in beta-catenin
      protein during the first 5 minutes with its translocation to the nucleus. We show
      this increase to be the result of decreased degradation of beta-catenin (decrease
      in serine phosphorylated beta-catenin) as seen by immunoprecipitation studies. We
      observed activation of beta-catenin degradation complex comprising of adenomatous
      polyposis coli gene product (APC) and serine-phosphorylated axin protein,
      beginning at 5 minutes after hepatectomy, leading to its decreased levels after
      this time. Quantitative changes observed in E-cadherin protein during liver
      regeneration are, in general, reverse to those seen in beta-catenin. In addition,
      using immunoprecipitation, we observe elevated levels of tyrosine-phosphorylated
      beta-catenin at 6 hours onward. Thus, changes in the wnt pathway during regulated
      growth seem to tightly regulate cytosolic beta-catenin levels and may be
      contributing to induce cell proliferation and target gene expression.
      Furthermore, these changes might also be intended to negatively regulate cell
      cell adhesion for structural reorganization during the process of liver
      regeneration.

PMID- 11343239
TI  - The role of p27kip1 protein expression on the biological behavior of intrahepatic
      cholangiocarcinoma.
AB  - Recent studies have reported that a decreased p27kip1 protein (p27) expression is
      associated with aggressive tumor behavior in several human malignancies. In this
      study, we examined the role of p27 expression in intrahepatic cholangiocarcinoma
      (ICC) and the noncancerous intrahepatic bile duct epithelium and assessed its
      association with clinicopathologic features, especially the influence of
      decreased p27 expression by the tumor on its prognosis as determined by
      immunohistochemistry. Almost all noncancerous bile duct epithelia show positive
      nuclear staining and reveal a faintly positive reaction in the cytoplasm. In 62
      surgically resected ICCs, a variable degree of positive p27 nuclear staining is
      recognized. A subset (13 of 62 cases; 21.0%) of the carcinomas displayed
      cytoplasmic staining. We classified 62 cases into 2 groups, a low expression
      group (< 50% of p27 nuclear positive cells) and a high expression group (> or =
      50% of p27 nuclear positive cells), and tested for the association between
      positive expression and clinicopathologic features. We found that a low
      expression of nuclear p27 was correlated with positive vascular invasion (P <
      .05). The survival curve of the group with low p27 nuclear expression was
      significantly lower than that of the group with high p27 nuclear expression (P <
      .005). According to the multivariate analyses, low p27 expression can be
      considered an independent prognostic factor whose occurrence indicates a worse
      prognosis. We conclude that a decreased p27 expression adds an independent
      parameter that can be used when determining the prognosis of patients with ICC.

PMID- 11343240
TI  - Increased risk of tumor seeding after percutaneous radiofrequency ablation for
      single hepatocellular carcinoma.
AB  - Radiofrequency (RF) ablation is an alternative to percutaneous ethanol injection
      (PEI) for single nonsurgical hepatocellular carcinoma (HCC) and is currently used
      as adjuvant therapy before liver transplantation. This phase II study assesses
      the treatment-related complications and response rate of RF for the treatment of
      single HCC < or = 5 cm. Percutaneous RF was performed under conscious sedation
      and ultrasound (US) guidance with an electrical generator connected to a single
      cooled-tip electrode. Neoplastic cells in peripheral blood (reverse transcription
      polymerase chain reaction for alpha fetoprotein [AFP] messenger RNA) were
      analyzed before and after RF. Treatment response was assessed by spiral computed
      tomography (CT) at 1 month and every 3 months by US or spiral CT thereafter.
      Thirty-two patients (20 men; age 67 +/- 4 years; 78% hepatitis C virus; 24 Child
      Pugh A) with a mean tumor size of 2.8 cm (25 patients < or = 3 cm) were treated
      by RF (1.25 sessions; mean time, 22.1 +/- 2 minutes). Adjuvant PEI was performed
      in 9 cases. Complete response was achieved in 21 patients (65%), being
      significantly higher for HCC < or = 3 cm (76% vs. 29%, P = .03). After a median
      follow-up of 10 months, 8 patients showed treatment-related morbidity. Four of
      them (12.5%) showed biopsy-proven needle-track seeding detected between 4 to 18
      months. Neoplastic seeding was related to subcapsular location (P = .009), poor
      differentiation degree (P = .02), and baseline AFP levels (P = .02). Thus, RF
      ablation with cooled-tip needle for HCC is associated with a high risk of
      neoplastic seeding. Iatrogenic dissemination was related to subcapsular location
      or an invasive tumoral pattern, and has to be considered when selecting curative
      treatments for HCC or adjuvant therapies before liver transplantation.

PMID- 11343241
TI  - Intracellular signaling pathways involved in acetaldehyde-induced collagen and
      fibronectin gene expression in human hepatic stellate cells.
AB  - Ethanol induces liver fibrosis by several means that include, among others, the
      direct fibrogenic action of acetaldehyde on hepatic stellate cells (HSC). However
      the mechanisms responsible for this effect are not well understood. In this
      communication we investigated signal transduction pathways triggered by
      acetaldehyde leading to upregulation of alpha2(I) collagen and fibronectin gene
      expression in human HSC. Run-on assays showed that acetaldehyde-enhanced
      transcription of these 2 genes as early as 2 hours, via de novo protein synthesis
      independent and -dependent mechanisms. It also stimulated a time-dependent
      induction in phosphorylation of pp70(S6K) and extracellular-regulated kinase
      (1/2) (ERK1/2). These effects were completely prevented by calphostin C, a
      protein kinase C inhibitor. As expected, acetaldehyde-elicited ERK1/2
      phosphorylation was inhibited by PD98059, a MEK inhibitor, but not by wortmannin,
      a PI3K inhibitor. On the other hand, both of these inhibitors partially inhibited
      phosphorylation of pp70(S6K) induced by acetaldehyde suggesting that its
      activation is ERK1/2- and PI3K-dependent. Acetaldehyde-elicited fibronectin and
      alpha2(I) collagen upregulation was inhibited by calphostin C. However, while
      PD98059, wortmannin and rapamycin (a pp70(S6K) inhibitor) completely abrogated
      alpha2(I) collagen upregulation, they had no effect on fibronectin expression.
      Overall, these data suggest that protein kinase C is an upstream component from
      which acetaldehyde signals are transduced to other pathways such as PI3K and
      ERK1/2. In addition, differential activation of these pathways is needed for the
      increase in fibronectin and alpha2(I) collagen gene expression induced by
      acetaldehyde in human HSC.

PMID- 11343242
TI  - Central venulitis in pediatric liver allografts.
AB  - Central venulitis (CV), a distinct histologic lesion described in adult liver
      transplants, can occur with acute portal tract rejection or in isolation (ICV).
      Possible etiologies include immunosuppressive drug toxicity, acute cellular
      rejection, viral hepatitis, ischemic injury, and recurrent disease. This study
      was designed to characterize ICV and to assess its potential etiology in
      pediatric liver recipients because this population generally does not develop
      recurrent disease or viral hepatitis. All posttransplantation liver biopsy
      specimens that were obtained from children who received liver allografts over a 4
      year period were reviewed. ICV was identified in 12 of 127 posttransplantation
      biopsies and in 7 of 45 allograft recipients. Only 4 liver transplantations were
      performed for potentially recurrent diseases (primary sclerosing cholangitis).
      ICV first appeared in posttransplantation biopsy specimens significantly later
      than did portal rejection alone. The finding of CV was not significantly
      correlated with elevation of Tacrolimus levels, reason for transplantation,
      donor/recipient cytomegalovirus (CMV) status or blood type, cold ischemic times,
      or the incidence of outflow obstruction. The responses of CV to therapy were
      variable and, although the majority of cases resolved, several episodes persisted
      or recurred. In conclusion, ICV occurs in 16% of pediatric liver allograft
      recipients and does not appear to be related to recurrent disease, viral
      hepatitis, drug toxicity, or graft ischemia. CV may be a variant of acute
      rejection, but longer follow-up is required to determine the most adequate
      therapy for this entity.

PMID- 11343243
TI  - Promoter polymorphism of the CD14 endotoxin receptor gene as a risk factor for
      alcoholic liver disease.
AB  - Twin concordance studies indicate that genetic factors influence the individual
      susceptibility for alcoholic liver disease (ALD). Both clinical and experimental
      data suggest that Kupffer cell activation by gut-derived endotoxins and other
      bacterial products is an important pathogenic factor. Activated Kupffer cells
      release proinflammatory cytokines, a process that is regulated by the CD14
      endotoxin receptor (CD14). Recently, a C-->T (-159) polymorphism in the promoter
      region of the CD14 gene was detected and found to confer increased CD14
      expression. In the present study, the association of CD14 promoter polymorphism
      with different forms of ALD was examined in 3 separate autopsy series. Among 442
      men with valid alcohol-consumption data, 381 men had been moderate or heavy
      alcohol consumers. The allele frequency of the CD14 promoter genotype, determined
      by a modified cycle minisequencing technique, was 0.34 (CC), 0.51 (CT), and 0.16
      (TT). The T allele was found to be associated with advanced ALD, i.e., with
      alcoholic hepatitis (odds ratio [OR]: 2.48; P = .018), and especially with
      cirrhosis (OR: 3.45; P = .004), but not with fatty liver, periportal fibrosis, or
      bridging fibrosis. The overall age-adjusted risk for cirrhosis was 3.08 (P = .01)
      for the carriers of the CT genotype, and 4.17 (P = .005) for the homozygous TT
      genotype. These results suggest that in the relatively isolated Finnish
      population, the T allele confers increased risk of alcoholic liver damage. In
      particular, TT homozygotes are at a high risk to develop cirrhosis.

PMID- 11343244
TI  - Malaria sporozoites actively enter and pass through rat Kupffer cells prior to
      hepatocyte invasion.
AB  - Malaria sporozoites have to cross the layer of sinusoidal liver cells to reach
      their initial site of multiplication in the mammalian host, the hepatocytes. To
      determine the sinusoidal cell type sporozoites use for extravasation, endothelia
      or Kupffer cells, we quantified sporozoite adhesion to and invasion of sinusoidal
      cells isolated from rat liver. In vitro invasion assays reveal that Plasmodium
      berghei and P. yoelii sporozoites attach to and enter Kupffer cells, but not
      sinusoidal endothelia. Unlike hepatocytes and other nonphagocytic cells, which
      are invaded in vitro only within the first hour of parasite exposure, the number
      of intracellular sporozoites in Kupffer cells increases for up to 12 hours. By
      confocal and electron microscopy, sporozoites are enclosed in a vacuole that does
      not colocalize with lysosomal markers. Inhibition of phagocytosis with gadolinium
      chloride has no effect on Kupffer cell invasion, but abolishes phagocytosis of
      inactivated sporozoites. Furthermore, sporozoites traverse in vitro from Kupffer
      cells to hepatocytes where they eventually develop into exoerythrocytic
      schizonts. Thus, malaria sporozoites selectively recognize and actively invade
      Kupffer cells, avoid phagosomal acidification, and safely passage through these
      phagocytes.

PMID- 11343245
TI  - Fas-induced apoptosis in mouse hepatocytes is dependent on C/EBPbeta.
AB  - Apoptotic cell death in the liver in response to activation of the Fas pathway
      has been implicated in human disease states as well as liver remodeling and
      tissue repair. C/EBPbeta, a member of the CCAAT enhancer binding protein family
      of bZIP transcription factors has been linked to both growth response and
      apoptotic targets in the liver, and, therefore, is a likely candidate for the
      regulation of apoptotic liver injury. We investigated differences in apoptotic
      cell death in the livers of C/EBPbeta-null mice using the Jo-2 agonistic anti-Fas
      antibody. Apoptotic injury was dramatically reduced in C/EBPbeta -/- livers as
      shown by a nearly 20-fold reduction in apoptotic hepatocytes 6 hours post-Jo-2
      treatment in C/EBPbeta -/- hepatocytes compared with controls (P < .04) and
      reduced activation of caspase 3. Bid cleavage occurred in Jo-2 treated C/EBPbeta 
      /- livers indicating a block of Fas-induced injury distal to the death-inducing
      signaling complex. The level of the antiapoptotic protein bcl-x(L) was increased
      greater than tenfold in the mutant animals (P < .04), which can, at least in
      part, account for the protection from Fas-mediated apoptosis. In contrast, bcl
      x(L) mRNA levels were unchanged. These observations link C/EBPbeta to Fas-induced
      hepatocyte apoptosis through a mechanism that likely involves translational or
      posttranslational regulation of bcl-x(L).

PMID- 11343246
TI  - Detoxification of reactive oxygen species by a nonpeptidyl mimic of superoxide
      dismutase cures acetaminophen-induced acute liver failure in the mouse.
AB  - Drug-induced acute liver failure (ALF) is a devastating and often fatal disease
      mainly caused by poisoning by acetaminophen (APAP). The toxic metabolite, N
      acetyl-p-benzoquinone-imine (NAPQI), that leads to gluthatione depletion has been
      suspected to be the main effector of hepatocyte apoptosis during APAP-induced
      ALF. We have investigated whether reactive oxygen species (ROS) also play a role
      in APAP-induced ALF, and whether manganese III tetrakis (5,10,15,20 benzoic acid)
      (MnTBAP), a mimic of superoxide dismutase (SOD) with catalase-like activity, can
      treat the disease in mice. The effects of MnTBAP were tested on APAP-intoxicated
      mice and on isolated hepatocytes incubated with APAP. MnTBAP preventively and
      curatively administered significantly improved survival times, and dramatically
      reduced serum transaminase activity levels and parenchymal lesions in APAP
      intoxicated mice. Whereas pretreatment with N-acetyl-L-cysteine (NAC) prevented
      ALF in a dose-dependent manner, the molecule was ineffective when curatively
      administered. The significant increase in glutathione peroxidase (Gpx) activity
      following APAP administration, and the beneficial effects of MnTBAP suggested
      that ROS were produced during APAP-induced ALF. A direct evidence of ROS
      generation was provided by flow cytometry of isolated hepatocytes incubated with
      APAP. In vitro, ROS production was associated with mitochondrial damage
      characterized by the collapse of transmembrane potential and the loss of
      cardiolipin content. In livers of intoxicated mice, ALF was associated with
      cytochrome c release that led to the activation of caspases-9 and -3. The
      capacity of MnTBAP to abrogate all those alterations suggests that ROS play a
      role in APAP-induced apoptosis of hepatocytes, and explains the beneficial
      effects of MnTBAP, which could be of interest in APAP-induced ALF in humans.

PMID- 11343247
TI  - Prolonged, but not acute, glutathione depletion promotes Fas-mediated
      mitochondrial permeability transition and apoptosis in mice.
AB  - Glutathione depletion either decreased or increased death-receptor-mediated
      apoptosis in previous studies. Comparison of the durations of glutathione
      depletion before death-receptor stimulation in these studies might suggest a
      different effect of prolonged versus acute thiol depletion. We compared the
      effects of the prolonged glutathione depletion caused by a sulfur amino acid
      deficient (SAA(-)) diet and the acute depletion caused by a single dose of
      phorone on hepatic apoptosis triggered by the administration of an agonistic anti
      Fas antibody. The chronic SAA(-) diet did not affect hepatic Fas or Bcl-XL, but
      increased p53 and Bax, and exacerbated Fas-mediated mitochondrial membrane
      depolarization, electron-microscopy-proven outer mitochondrial membrane rupture,
      cytochrome c translocation to the cytosol, and caspase 3 activation. These
      effects were prevented by cyclosporin A, an inhibitor of mitochondrial
      permeability transition. The SAA(-) diet increased internucleosomal DNA
      fragmentation, the percentage of apoptotic hepatocytes, serum alanine
      transaminase (ALT) activity, and mortality after Fas stimulation. Despite a
      similar decrease in hepatic glutathione, administration of a single dose of
      phorone 1 hour before the anti-Fas antibody did not change p53 or Bax, and did
      not enhance Fas-induced mitochondrial permeability transition and toxicity.
      However, 4 repeated doses of phorone (causing more prolonged glutathione
      depletion) increased Bax and Fas-mediated toxicity. In conclusion, a chronic SAA(
      ) diet, but not acute phorone administration, increases p53 and Bax, and enhances
      Fas-induced mitochondrial permeability transition and apoptosis. Thiol depletion
      could cause oxidative stress that requires several hours to increase p53; the
      latter induces Bax, which translocates to mitochondria after Fas stimulation.

PMID- 11343248
TI  - Effects of treatment with deoxycholic acid and chenodeoxycholic acid on the
      hepatic synthesis of cholesterol and bile acids in healthy subjects.
AB  - The degradation of cholesterol to bile acids is regulated by a negative-feedback
      mechanism by the bile acids, especially the hydrophobic bile acids, returning to
      the liver via the portal vein. Chenodeoxycholic acid (CDCA) is a potent
      suppressor of the cholesterol 7alpha-hydroxylase, the rate-determining enzyme in
      bile acid formation. CDCA may also suppress hepatic 3-hydroxy-3-methyl glutaryl
      coenzyme A (HMG CoA) reductase, the rate-limiting enzyme in cholesterol
      synthesis. Conflicting reports have appeared regarding the suppression on bile
      acid synthesis by the most hydrophobic bile acid of human bile, deoxycholic acid
      (DCA). To study the suppressive effects of CDCA and DCA on hepatic cholesterol
      and bile acid synthesis in humans, 10 healthy subjects were treated with CDCA or
      DCA for 3 weeks in a randomized cross-over study with a washout period of 4 weeks
      in between. Serum levels of 7alpha-hydroxy-4-cholesten-3-one, reflecting
      cholesterol 7alpha-hydroxylase activity, and 7-dehydrocholesterol, reflecting HMG
      CoA reductase activity, and bile acids were repeatedly measured during the study
      periods. After 3 weeks of treatment with CDCA or DCA, CDCA constituted 70% and
      DCA 74% of the total serum bile acids, respectively. CDCA and DCA decreased the
      serum levels of 7alpha-hydroxy-4-cholesten-3-one by 80% and 75%, respectively.
      Negative correlations between the percentages of CDCA and DCA and the serum
      concentration of 7alpha-hydroxy-4-cholesten-3-one were obtained. CDCA reduced the
      serum level of 7-dehydrocholesterol by 29%, whereas treatment with DCA tended to
      increase the level of 7-dehydrocholesterol. Treatment of healthy subjects with
      CDCA and DCA reduces bile acid synthesis. CDCA also inhibits cholesterol
      synthesis, whereas DCA does not.

PMID- 11343249
TI  - Etiologic significance of defects in cholesterol, phospholipid, and bile acid
      metabolism in the liver of patients with intrahepatic calculi.
AB  - Intrahepatic calculi, highly prevalent in the Far East, including Japan, are
      characterized clinically by chronic proliferative cholangitis with frequent stone
      recurrences. Intrahepatic calculi consist of 2 groups, i.e., brown pigment
      stones, including a high cholesterol content, and cholesterol stones, with the
      former predominating. To gain insights into the pathogenesis of intrahepatic
      calculi, cholesterol and bile acid biosynthesis, as well as alterations in
      intracellular transport and/or canalicular secretion of phospholipid and bile
      acid were investigated in liver of patients with intrahepatic calculi. Enzyme
      activities of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase were
      increased (12.8 +/- 1.9 pmol/min/mg protein, mean +/- SEM vs. 5.5 +/- 0.4 in
      controls; P < .01) and cholesterol 7 alpha-hydroxylase activities were decreased
      (1.3 +/- 0.4 vs. 4.9 +/- 0.6; P < .01) in liver specimens of patients with brown
      pigment stones. In addition, messenger RNA (mRNA) levels of multidrug resistance
      P-glycoprotein 3 (MDR3 Pgp) and phosphatidylcholine transfer protein (PCTP) were
      markedly low in the liver specimens compared with the levels in specimens of
      control subjects, gallbladder stone patients, and patients with obstructive
      cholestasis. The protein levels and the immunohistochemical staining were
      decreased for MDR3 Pgp and PCTP in the liver. Consistently, the concentrations of
      phospholipid were markedly reduced in the hepatic bile from both affected and
      unaffected hepatic segments. In patients with intrahepatic calculi, biliary
      cholesterol supersaturation and the formation of cholesterol-rich brown pigment
      as well as cholesterol stones may be attributed to decreased hepatic transport
      and biliary secretion of phospholipids, in the setting of increased
      cholesterogenesis and decreased bile acid synthesis.

PMID- 11343250
TI  - Tauroursodeoxycholic acid inserts the apical conjugate export pump, Mrp2, into
      canalicular membranes and stimulates organic anion secretion by protein kinase C
      dependent mechanisms in cholestatic rat liver.
AB  - Ursodeoxycholic acid (UDCA) exerts anticholestatic effects by undefined
      mechanisms. Previous work suggested that UDCA stimulates biliary exocytosis via
      Ca(++)- and protein kinase C (PKC)-dependent mechanisms. Therefore, the effect of
      taurine-conjugated UDCA (TUDCA) was studied in the experimental model of
      taurolithocholic acid (TLCA)-induced cholestasis on bile flow, hepatobiliary
      exocytosis, distribution of PKC isoforms, and density of the apical conjugate
      export pump, Mrp2, in canalicular membranes. Isolated perfused rat livers were
      preloaded with horseradish peroxidase (HRP), a marker of vesicular exocytosis,
      and were perfused with bile acids or dimethylsulfoxide (control) only. PKC
      isoform distribution and membrane density of Mrp2 were studied using
      immunoblotting and immunoelectron-microscopic techniques. Biliary secretion of
      the Mrp2 substrate, 2,4-dinitrophenyl-S-glutathione (GS-DNP), was studied in the
      presence or absence of the PKC inhibitor, bisindolylmaleimide I (BIM-I; 1
      micromol/L). TLCA (10 micromol/L) impaired bile flow by 51%; biliary secretion of
      HRP and GS-DNP by 46% and 95%, respectively; membrane binding of the Ca(++)
      sensitive alpha-isoform of PKC by 32%; and density of Mrp2 in the canalicular
      membrane by 79%. TUDCA (25 micromol/L) reversed the effects of TLCA on bile flow,
      secretion of HRP and GS-DNP, and distribution of alpha-PKC. TUDCA reduced
      membrane binding of epsilon-PKC and increased Mrp2 density 4-fold in canalicular
      membranes of cholestatic hepatocytes. BIM-I inhibited the effect of TUDCA on GS
      DNP secretion in cholestatic livers by 49% without affecting secretion in
      controls. In conclusion, TUDCA may enhance the secretory capacity of cholestatic
      hepatocytes by stimulation of exocytosis and insertion of transport proteins into
      apical membranes via PKC-dependent mechanisms.

PMID- 11343251
TI  - Zinc mesoporphyrin represses induced hepatic 5-aminolevulinic acid synthase and
      reduces heme oxygenase activity in a mouse model of acute hepatic porphyria.
AB  - Zinc mesoporphyrin (ZnMP) is a potent inhibitor of heme oxygenase (HO) and
      represses 5-aminolevulinic acid synthase (ALAS). These properties make it a
      potential candidate for treatment of inducible acute hepatic porphyrias, diseases
      characterized by neurovisceral symptoms, and massive ALAS induction. Effects of
      intraperitoneal ZnMP (2.5-10 micromol/kg/d) and heme arginate (3-6 mg/kg/d) on
      plasma levels of 5-aminolevulinic acid (ALA), on messenger RNA (mRNA), and
      activity of hepatic ALAS and HO were studied in porphobilinogen deaminase
      deficient mice treated with phenobarbital (100 mg/kg/d) to induce ALAS. ZnMP (5
      micromol/kg/d) led to a significant reduction of plasma ALA levels to 31% of
      controls (P < .01) by lowering the activity of hepatic mitochondrial and
      cytosolic ALAS to 29% and 25% of controls, respectively (P < .03). ZnMP decreased
      the mRNA levels of hepatic ALAS to 53% (P < .03) of controls and this repression
      was more pronounced than that achieved with heme arginate. In contrast to heme
      arginate, ZnMP led to a significant reduction of HO activity. We conclude that
      the combined effect of ZnMP on highly induced ALAS and on HO may be of potential
      benefit for human acute hepatic porphyrias and therefore merits further in vivo
      investigations addressing questions raised by this study.

PMID- 11343252
TI  - Characterization of the mouse bile salt export pump overexpressed in the
      baculovirus system.
AB  - The bile salt export pump (Bsep), a member of the ATP-binding cassette
      superfamily of transporters, mediates the ATP-dependent canalicular secretion of
      bile salts. We have cloned and expressed the mouse Bsep (mBsep) protein in Sf9
      insect cells, and characterized its transport and ATPase properties. Because its
      deduced amino acid sequence predicts multiple phosphorylation sites for protein
      kinase A, protein kinase C (PKC) and Ca(2+)-calmodulin dependent kinase II, we
      have also tested whether mBsep undergoes phosphorylation. MBsep transports both
      glycine and taurine conjugated bile salts. Sf9 cell membranes that express mBsep
      exhibit higher basal ATPase activity than control membranes, and this is further
      stimulated by bile salts and inhibited by vanadate. Taurochenodeoxycholate is
      transported with the highest affinity and is the most potent inducer of ATPase
      activity. Cyclosporin A, glibenclamide and rifamycin SV, all competitive
      inhibitors of Bsep transport, also reduced the bile salt-stimulated ATPase
      activity. MBsep exists as a phospho-protein when expressed in Sf9 cells and the
      immunoprecipitated mBsep complex is a substrate for the catalytic subunit of PKC.
      When mBsep and the alpha-isoform of mouse PKC are co-expressed in Sf9 cells, a
      ninefold stimulation of phosphorylation occurs. This is further increased to 18
      fold after activation by phorbol ester. Given that bile salts activate selected
      PKC isoforms in hepatocytes, including the alpha isoform, the phosphorylation of
      mBsep by PKCalpha may represent a point of regulation for this transporter that
      is mediated by its own substrate.

PMID- 11343253
TI  - The phenobarbital response enhancer module in the human bilirubin UDP
      glucuronosyltransferase UGT1A1 gene and regulation by the nuclear receptor CAR.
AB  - The UDP-glucuronosyltransferase, UGT1A1, is the critical enzyme responsible for
      detoxification of the potentially neurotoxic bilirubin by conjugating it with
      glucuronic acid. For decades, phenobarbital (PB) treatment for hyperbilirubinemia
      has been known to increase expression of the UGT1A1 gene in liver. We have now
      delineated the PB response activity to a 290-bp distal enhancer sequence (-3483/
      3194) of the UGT1A1 gene. The enhancer contains 3 putative nuclear receptor
      motifs, and it was activated by the nuclear orphan receptor, human constitutive
      active receptor (hCAR), in cotransfected HepG2 cells. Bacterially expressed hCAR,
      acting as a heterodimer with in vitro-translated retinoid X receptor (RXRalpha),
      only bound to 1 of the 3 NR motifs, named gtNR1 in a gel-shift assay.
      Consistently, mutations of the gtNR1 site significantly decreased the activation
      by hCAR of the 290-bp DNA in transfection assays. Moreover, the 290-bp DNA was
      effectively activated in mouse primary hepatocytes in response to PB, offering an
      excellent clinical test for the examination of the responsiveness of the UGT1A1
      to PB in the human population, particularly individuals with hyperbilirubinemia.

PMID- 11343254
TI  - RNA expression in the early characterization of hepatotoxicants in Wistar rats by
      high-density DNA microarrays.
AB  - High-density microarrays are useful tools to study gene expression for the
      purpose of characterizing functional tissue changes in response to the action of
      drugs and chemicals. To test whether high-density expression data can identify
      mechanisms of toxicity and to identify an unknown sample through its RNA
      expression pattern, groups of male Wistar rats were administered 6
      hepatotoxicants. The compounds chosen for this study were microcystin-LR (MLR),
      phenobarbital (PB), lipopolysaccharide (LPS), carbon tetrachloride (CT),
      thioacetamide (THA), and cyproterone acetate (CPA). These hepatotoxicants are
      known to induce adverse liver effects through different mechanisms. Liver mRNA
      was isolated and used to generate biotinylated cRNA for hybridization to a custom
      1,600-rat gene DNA microarray. Treatment correlation matrices analyzed
      hybridization data from a hepatotoxicant-blinded sample, with gene expression
      coefficients (GEC) evaluated by means of hierarchical cluster analysis and visual
      representation as dendrograms. The experimental liver toxicity from the different
      treatments was confirmed by means of concurrent histopathology, liver enzymes,
      and bilirubin assays. This toxico genomic analysis identified multiple genes and
      groups of genes that were affected by the hepatotoxicants on study, indicating
      that high-density microarray expression data are useful to identify groups of
      genes involved in toxicity. In addition, the mRNA expression profile of an
      unidentified sample can be accurately identified when compared with the
      expression profiles resident in the data set. This study supports the use of gene
      expression-profiling technology to determine or to predict toxic liver effects.

PMID- 11343255
TI  - Morphologic and functional characterization of caveolae in rat liver hepatocytes.
AB  - Caveolae are small pits on the plasma membrane found in several, if not all,
      differentiated cells. They are involved in potocytosis, endocytosis,
      transcytosis, membrane trafficking, and signal transduction. Although caveolin
      has recently been identified in subcellular fractions from rat liver there is no
      clear-cut morphologic evidence for the presence of prototypical caveolae on the
      surface of hepatocytes. In this study the presence of caveolae at the cell
      surface of hepatocytes was directly shown by rapid-freeze, deep-etching electron
      microscopy. Moreover, combined deep-etching and immunogold techniques revealed
      caveolin in caveolae of the dorsal membrane of primary culture hepatocytes. Using
      reagents that perturb membrane cholesterol and interfere with endocytosis through
      the caveolae, a caveolae-dependent internalization of cholera toxin B and retinol
      binding protein by hepatocytes in primary culture was shown. Finally,
      immunocytochemical analysis of caveolin in nonparenchymal cells of the rat liver
      showed its presence in Kupffer and stellate cells, however no caveolin could be
      detected in endothelial cells.

PMID- 11343257
TI  - Expression of hepatitis C virus proteins does not interfere with major
      histocompatibility complex class I processing and presentation in vitro.
AB  - Hepatitis C virus (HCV) infection takes a chronic course in the majority of
      patients. The mechanisms underlying the evasion of the host immune response and
      viral persistence are poorly understood. In this context, we investigated
      interactions of HCV proteins with major histocompatibility complex (MHC) class I
      processing and presentation pathways using cell lines that allow the tetracycline
      regulated expression of viral structural and nonstructural proteins. These well
      characterized inducible cell lines were found to efficiently process and present
      endogenously synthesized HCV proteins via MHC class I. Functional MHC class I
      cell-surface expression and intracellular proteasome activity were not affected
      by the expression of HCV proteins. These results suggest that viral evasion of
      the host immune response does not involve interactions of HCV with MHC class I
      processing and presentation. Other mechanisms, such as interference with the
      interferon system, may be operative in HCV infection, leading to viral
      persistence.

PMID- 11343256
TI  - The hepatitis B virus X protein (HBx) induces a migratory phenotype in a CD44
      dependent manner: possible role of HBx in invasion and metastasis.
AB  - The hepatitis B virus X protein (HBx) of the hepatitis B virus (HBV) has been
      involved in the development of hepatocellular carcinoma (HCC). However, its
      possible contribution to the metastatic spreading of liver tumors has not been
      explored so far. We report here the ability of HBx to enhance cell motility, both
      alone and in synergy with growth factors, and to induce a migratory phenotype in
      transformed cells. HBx altered the cellular morphology by inducing the formation
      of pseudopodial protrusions and cytoskeletal rearrangements, which was
      accompanied by the polarization of cell-surface adhesion molecules, including the
      hyaluronan (HA) receptor, CD44. Furthermore, HBx induced the redistribution to
      the pseudopodial tips of F-actin-binding proteins of the ezrin/radixin/moesin
      (ERM) family in a Rho- and Rac-dependent manner and increased the association of
      CD44 with moesin. The migration of HBx-bearing cells in response to HA and growth
      factors was impaired by a blocking anti-CD44 monoclonal antibody (mAb),
      suggesting that the HBx-induced cell motility is partially mediated by CD44.
      Interestingly, HBx-bearing cells showed increased HA-interaction efficiency as
      assessed under laminar flow conditions, which was the result, at least in part,
      of an enhanced binding affinity of CD44. HBx may therefore contribute to the
      acquisition of metastatic properties by modifying the migratory behavior of
      transformed hepatocytes and by increasing their ability to bind HA in the outer
      margin of the tumors or in secondary target organs.

PMID- 11343258
TI  - A molecular comparison of T lymphocyte populations infiltrating the liver and
      circulating in the blood of patients with chronic hepatitis B: evidence for
      antigen-driven selection of a public complementarity-determining region 3 (CDR3)
      motif.
AB  - Despite a large number of T cells infiltrating the liver of patients with chronic
      hepatitis B, little is known about their complexity or specificity. To
      characterize the composition of these T cells involved with the pathogenesis of
      chronic hepatitis B (CHB), we have studied the clonality of VbetaT cell receptor
      (TCR)-bearing populations in liver tissue by size spectratyping the
      complementarity-determining region (CDR3) lengths of TCR transcripts. We have
      also compared the CDR3 profiles of the lymphocytes infiltrating the liver with
      those circulating in the blood to see whether identical clonotypes may be
      detected that would indicate a virus-induced expansion in both compartments. Our
      studies show that in most of the patients examined, the T cell composition of
      liver infiltrating lymphocytes is highly restricted, with evidence of clonotypic
      expansions in 4 to 9 TCR Vbeta subfamilies. In contrast, the blood compartment
      contains an average of 1 to 3 expansions. This pattern is seen irrespective of
      the patient's viral load or degree of liver pathology. Although the TCR
      repertoire profiles between the 2 compartments are generally distinct, there is
      evidence of some T cell subsets being equally distributed between the blood and
      the liver. Finally, we provide evidence for a putative public binding motif
      within the CDR3 region with the sequence G-X-S, which may be involved with
      hepatitis B virus recognition.

PMID- 11343259
TI  - Long-term follow-up study of sustained biochemical responders with interferon
      therapy.
AB  - A proportion of chronic hepatitis C patients who were treated with interferon
      have a sustained normalization of transaminase levels after interferon therapy
      without hepatitis C virus (HCV)-RNA clearance. We determined their clinical
      characteristics and long-term outcome in relation to progression to liver
      cirrhosis (LC) and the development of hepatocellular carcinoma (HCC). A total of
      250 patients with chronic hepatitis C who were treated with interferon were
      studied for 8 to 11 years' posttherapy. Sixty-seven patients (27%) were complete
      responders with clearance of HCV RNA. Twenty-six (10%) were biochemical
      responders who had sustained normal alanine transaminase (ALT) levels without
      viral clearance. The remaining patients were short-term responders (n = 70) and
      nonresponders (n = 87). Biochemical responders were older, had higher levels of
      pretreatment HCV RNA in serum than complete responders, and had less advanced
      liver histology than nonresponders. Histologic grading scores decreased
      significantly at the end of therapy, while the staging scores did not change
      significantly. The annual incidence of cirrhosis was 0% in biochemical and
      complete responders, which was significantly lower than nonresponders and the
      controls (P = .0001). The annual incidence of HCC was 0.37% in complete
      responders and 0.50% in biochemical responders, which was significantly lower
      than nonresponders (P = .0001 for both). Our findings suggest that biochemical
      responders had high pretreatment viral levels with less advanced liver histology,
      and their long-term outcome appeared to be good irrespective of the persistence
      of the virus.

PMID- 11343260
TI  - SEN virus infection and its relationship to transfusion-associated hepatitis.
AB  - SEN virus (SEN-V) is a recently identified single-stranded, circular DNA virus.
      Two SEN-V variants (SENV-D and SENV-H) were assayed by polymerase chain reaction
      (PCR) to investigate their role in the causation of transfusion-associated non-A
      to E hepatitis. The incidence of SEN-V infection after transfusion was 30% (86 of
      286) compared with 3% (3 of 97) among nontransfused controls (P < .001).
      Transfusion risk increased with the number of units transfused (P < .0001) and
      donor-recipient linkage for SEN-V was shown by sequence homology. The prevalence
      of SEN-V in 436 volunteer donors was 1.8%. Among patients with transfusion
      associated non-A to E hepatitis, 11 of 12 (92%) were infected with SEN-V at the
      time of transfusion compared with 55 of 225 (24%) identically followed recipients
      who did not develop hepatitis (P < .001). No effect of SEN-V on the severity or
      persistence of coexistent hepatitis C virus (HCV) infection was observed. In 31
      infected recipients, SEN-V persisted for greater than 1 year in 45% and for up to
      12 years in 13%. SEN-V-specific RNA (a possible replicative intermediate) was
      recovered from liver tissue. In summary, SENV-D and -H were present in nearly 2%
      of US donors, and were unequivocally transmitted by transfusion and frequently
      persisted. The strong association of SEN-V with transfusion-associated non-A to E
      hepatitis compared with controls raises the possibility, but does not establish
      that SEN-V might be a causative agent of posttransfusion hepatitis. The vast
      majority of SEN-V-infected recipients did not develop hepatitis.

PMID- 11343261
TI  - Characterization of liver T-cell receptor gammadelta T cells obtained from
      individuals chronically infected with hepatitis C virus (HCV): evidence for these
      T cells playing a role in the liver pathology associated with HCV infections.
AB  - The pathogenic mechanisms involved in viral hepatitis are not completely
      understood. Evidence suggests that the pathology associated with hepatitis C
      virus (HCV) and hepatitis B virus (HBV) infections are a result of the immune
      response in the liver to these viruses. The livers of patients with viral
      hepatitis have been shown to contain elevated numbers of T cells expressing the
      gamma/delta form of the T-cell receptor for antigen (TCRgammadelta). In this
      study, we investigated whether liver biopsy specimens obtained from individuals
      with viral (HCV and/or HBV) or nonviral hepatitis contained TCRgammadelta(+) T
      cells that could be expanded in vitro by cytokines. A high percentage of liver
      biopsy specimens obtained from HCV- and/or HBV-infected individuals contained
      high numbers of TCRgammadelta(+) T cells. In contrast, T-cell lines generated
      from liver biopsy tissues obtained from individuals with nonviral hepatitis or
      from normal controls had no preferential expansion of TCRgammadelta(+) T cells.
      Liver TCRgammadelta(+) T-cell lines from HCV-infected individuals had high levels
      of non-major histocompatibility complex (MHC)-restricted cytotoxic activity
      against different targets including primary hepatocytes and produced interferon
      gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), and interleukin 8 (IL
      8) following activation by anti-CD3. Surprisingly, none of these liver
      TCRgammadelta(+) T-cell lines could recognize any of the structural or
      nonstructural proteins of HCV and had no cytotoxic activity against cells
      infected with recombinant vaccinia viruses expressing different HCV proteins.
      However, the crosslinking of CD81, which has been shown to bind HCV particles and
      E2, resulted in significant levels of IFN-gamma and TNF-alpha production by liver
      TCRgammadelta(+) T cells. These results suggest that TCRgammadelta(+) T cells may
      play a role in the liver pathology of HCV infections.

PMID- 11343262
TI  - Diagnosis and management of hemochromatosis.

PMID- 11343263
TI  - Central venulitis in liver allografts: considerations of differential diagnosis.

PMID- 11343264
TI  - Hepatic Kupffer cells: the portal that permits infection of hepatocytes by
      malarial sporozoites?

PMID- 11343265
TI  - Microbial rank.

PMID- 11343266
TI  - Radiofrequency ablation for hepatocellular carcinoma: help or hazard?

PMID- 11343267
TI  - Antidiabetic treatment for NASH?

PMID- 11343268
TI  - Is splenectomy a cause of antiviral treatment failure in hepatitis C virus
      infection?

PMID- 11343269
TI  - Amniocentesis as a possible risk factor for mother-to-infant transmission of
      hepatitis C virus.

PMID- 11343271
TI  - Acute tumor lysis syndrome.

PMID- 11343272
TI  - Management of acute tumor lysis syndrome.

PMID- 11343273
TI  - Role of intravenous allopurinol in the management of acute tumor lysis syndrome.

PMID- 11343274
TI  - Pharmacoeconomic considerations in the management of acute tumor lysis syndrome.

PMID- 11343275
TI  - Comparative interaction of alpha-helical and beta-sheet amphiphilic isopeptides
      with phospholipid monolayers.
AB  - The two sequential amphiphilic peptide isomers, (Leu-Lys-Lys-Leu)4 and (Leu
      Lys)8, were chosen as models for alpha-helical and beta-sheet peptides,
      respectively. In order to evaluate the contribution of the secondary structure of
      a peptide to its penetration into cellular membranes, interactions of these
      isopeptides with L-alpha-dimyristoyl phosphatidylcholine (DMPC) monolayers were
      studied. Both isopeptides penetrate into DMPC monolayers up to an exclusion
      pressure of approximately 27 mN/m, but a discontinuity is observed in the
      penetration profile of the alpha-helical (LKKL)4. The main parameters extracted
      from the compression isotherms of the mixed peptide/DMPC monolayers-namely,
      transition pressure, mean area, elasticity modulus, and energy of mixing-were
      analyzed. These analyses indicate that the alpha-helical isomer interacts
      strongly with DMPC by forming a 1:32 (LKKL)4-DMPC complex. When engaged in this
      complex, (LKKL)(4) behaves as an hydrophobic helix and has a tendency to become
      vertically oriented in the course of the compression process. The beta-sheet
      (LK)8 interacts more weakly with DMPC and no complex can be detected.

PMID- 11343276
TI  - Effect of glycosylation on structure and dynamics of MHC class I glycoprotein: a
      molecular dynamics study.
AB  - Complex carbohydrates linked to glycoproteins are recently being implicated to
      play a variety of biological roles. The lack of well-resolved crystallographic
      coordinates of the carbohydrates makes it difficult to assess the contributions
      of the glycan chain on protein structure and dynamics. We have modeled two
      different oligosaccharides NeuNAc2Gal3Man3GlcNAc5Fuc and Man3GlcNAc4 to generate
      two glycosylation variants of major histocompatibility complex (MHC) class I
      glycoprotein. Molecular dynamics simulations of the isolated fourteen- and seven
      residue oligosaccharides have been done in vacuo and in solution. The dynamics of
      the two glycoforms of MHC class I protein have been simulated in solution in the
      free as well as in the peptide-bound form. Good agreement between the calculated
      solution conformations of the oligosaccharides in isolated and conjugated forms
      and the average conformations obtained from x-ray or NMR data was observed for
      most of the glycosidic linkages. These molecular dynamics simulations of the
      isolated glycan chains and the glycoconjugates reveal the details of the
      conformational flexibility of the glycan chains; they also provide atomic level
      details of protein-carbohydrate interactions and the effect of the ligand binding
      on the carbohydrate structure and dynamics. It was found that though there is
      some flexibility in some of the glycosidic linkages in the isolated
      oligosaccharides, in the protein-conjugated form the linkages adopt more
      restricted conformations. The glycan chains protrude out into the solvent and
      might hinder the lateral association of the proteins. The presence of the bulky
      glycan chains does not affect the average backbone fold of the protein but
      induces local changes in protein structure and dynamics. It has been noted that
      the extent of the changes depends upon the nature of the attached glycan chain.
      The glycan chains do not appear to influence the peptide binding property of the
      protein directly, but may stabilize the protein residues that are involved in
      ligand binding.

PMID- 11343277
TI  - Contribution of tertiary amides to the conformational stability of collagen
      triple helices.
AB  - The collagen triple helix is composed of three polypeptide strands, each with a
      sequence of repeating (Xaa-Yaa-Gly) triplets. In these triplets, Xaa and Yaa are
      often tertiary amides: L-proline (Pro) and 4(R)-hydroxy-L-proline (Hyp). To
      determine the contribution of tertiary amides to triple-helical stability, Pro
      and Hyp were replaced in synthetic collagen mimics with a non-natural acyclic
      tertiary amide: N-methyl-L-alanine (meAla). Replacing a Pro or Hyp residue with
      meAla decreases triple-helical stability. Ramachandran analysis indicates that
      meAla residues prefer to adopt straight phi and psi angles that are dissimilar
      from those of the Pro and Hyp residues in the collagen triple helix. Replacement
      with meAla decreases triple-helical stability more than does replacement with
      Ala. All of the peptide bonds in triple-helical collagen are in the trans
      conformation. Although an Ala residue greatly prefers the trans conformation, a
      meAla residue exists as a nearly equimolar mixture of trans and cis conformers.
      These findings indicate that the favorable contribution of Pro and Hyp to the
      conformational stability of collagen triple helices arises from factors other
      than their being tertiary amides.

PMID- 11343278
TI  - Chemical synthesis of cross-linked poly(KGGVG), an elastin-like biopolymer.
AB  - Previous studies afforded on peptides and polypeptides containing repetitive
      sequences of elastin have largely demonstrated that their molecular and
      supramolecular properties are fully representative of those of tropoelastin, the
      soluble, linear precursor of elastin itself. In the attempt to synthesize cross
      linked elastin-mimetic polypeptides, the repeating sequence VGGVG (V: valine; G:
      glycine), typical of elastin, was modified to incorporate lysine residues,
      yielding the polymer poly(KGGVG) (K: lysine). This imparts primary amine
      functionality susceptible to cross-linking reaction with appropriate bifunctional
      cross-linking reagents. We report herein the chemical synthesis and cross-linking
      of poly(KGGVG) with glutaraldehyde (GTA) and with disuccinimidyl glutarate (DSG).
      In both cases, the characterization of the polymers, both linear and cross
      linked, has been carried out by CD spectroscopy and transmission electron
      microscopy measurements. The obtained results, although not conclusive,
      demonstrate that poly(KGGVG), both linear and cross-linked, may be considered
      very similar to tropoelastin and mature elastin, as concerns its molecular and
      supramolecular properties.

PMID- 11343279
TI  - Gelation behaviour of konjac glucomannan with different molecular weights.
AB  - The deacetylation and gelation of konjac glucomannan (KGM) following alkali
      addition was investigated by Fourier transform infrared, while the rheological
      properties of KGM with different molecular weights were studied by dynamic
      viscoelastic measurements in shear mode and penetration force tests. It was found
      that gelation occurred after significant deacetylation had taken place.
      Rheometrical studies revealed that KGM with different molecular weights exhibited
      different gelation characteristics in small amplitude oscillatory shear flow. For
      the samples of fractionated KGM with lower molecular weights, a decrease in both
      the storage shear modulus (G') and loss shear modulus (G") was observed during
      gelation at temperatures above 75 degrees C. It is suggested that the decrease
      results from the wall slip between sample and measuring geometry owing to a rapid
      gelation process with syneresis and/or disentanglement of molecular chains
      adsorbed on the surface of parallel plates from those located in the bulk.
      Penetration force tests were employed to confirm the occurrence of slippage and
      thereby no decreases in rigidity of samples were observed during gelation. For
      the native KGM samples decreases in G' and G" during gelation were not observed,
      and it is suggested that this is due to the effect of the higher molecular weight
      and increased solution viscosity of these samples on the gelation kinetics.

PMID- 11343280
TI  - Interaction of processes on different length scales in a bioelastomer capable of
      performing energy conversion.
AB  - This work concerns the aggregation properties of (Gly-Val-Gly-Val-Pro)(251) rec,
      a polypentapeptide reflecting a highly conserved repetitive unit of the
      bioelastomer, elastin. On raising the temperature of aqueous solutions above 25
      degrees C, this polypeptide was already known to undergo concurrent
      conformational changes (hydrophobic folding), phase separation, and self-assembly
      with formation of aggregated three-stranded filaments composed of dynamic
      polypeptide helices, called beta-spirals. Aggregates obtained from the solution
      can be shaped into bands that acquire entropic elastic properties upon gamma
      irradiation and can perform a variety of energy conversions. Previous studies
      have shown that aggregation is prompted by the (diverging) critical fluctuations
      of concentration occurring in the solution, in vicinity of its spinodal line.
      Here, we present combined circular dicroism (CD) and light scattering
      experiments, and independent fittings of experimental data to the theoretical
      spinodal and binodal (coexistence) lines. Results show the following logical and
      causal sequence of processes: (a) Smooth and progressive conformational changes
      promoted by concentration fluctuations occurring as temperature is raised "pull
      down" (in the temperature scale) the instability region of the solution. (b) This
      further promotes critical fluctuations. (c) The related locally high
      concentration prompts a further substantial conformational change ending in
      triple-helix formation and coacervation. (d) This intertwining of processes,
      covering different length scales (from that of individual peptides to the
      mesoscopic one of demixed regions), is related to the fact that solvent-induced
      interactions play a strong role over the entire scale span. These results concur
      with other recent ones in pointing out that process interactions over many length
      scales probably reflect a frequent if not ubiquitous pattern in protein
      aggregation. This may be highly relevant to the desirable deep understanding of
      such phenomenon, whose interests cover many fields.

PMID- 11343281
TI  - Differential interactions of antitumor antibiotics chromomycin A(3) and
      mithramycin with d(TATGCATA)(2) in presence of Mg(2+).
AB  - The antitumor antibiotics chromomycin A(3) (CHR) and mithramycin (MTR) are known
      to inhibit macromolecular biosynthesis by reversibly binding to double stranded
      DNA with a GC base specificity via the minor groove in the presence of a divalent
      cation such as Mg(2+). Earlier reports from our laboratory showed that the
      antibiotics form two types of complexes with Mg(2+): complex I with 1:1
      stoichiometry and complex II with 2:1 stoichiometry in terms of the antibiotic
      and Mg(2+). The binding potential of an octanucleotide, d(TATGCATA)(2), which
      contains one potential site of association with the above complexes of the two
      antibiotics, was examined using spectroscopic techniques such as absorption,
      fluorescence, and circular dichroism. We also evaluated thermodynamic parameters
      for the interaction. In spite of the presence of two structural moieties of the
      antibiotic in complex II, a major characteristic feature was the association of a
      single ligand molecule per molecule of octameric duplex in all cases. This
      indicated that the modes of association for the two types of complexes with the
      oligomeric DNA were different. The association was dependent on the nature of the
      antibiotics. Spectroscopic characterization along with analysis of binding and
      thermodynamic parameters showed that differences in the mode of recognition by
      complexes I and II of the antibiotics with polymeric DNA existed at the
      oligomeric level. Analysis of the thermodynamic parameters led us to propose a
      partial accommodation of the ligand in the groove without the displacement of
      bound water molecules and supported earlier results on the DNA structural
      transition from B --> A type geometry as an obligatory requirement for the
      accommodation of the bulkier complex II of the two drugs. The role of the
      carbohydrate moieties of the antibiotics in the DNA recognition process was
      indicated when we compared the DNA binding properties with the same type of
      Mg(2+) complex for the two antibiotics.

PMID- 11343282
TI  - Noninvasive characterization of human stratum corneum of undiseased skin of
      patients with atopic dermatitis and psoriasis as studied by Fourier transform
      Raman spectroscopy.
AB  - Etiopathogenetic regulatory disorders of epidermal metabolism and the subsequent
      changes in the molecular pattern of the stratum corneum play an important role in
      the clinical differentiation of particular dermatoses (e.g., psoriasis, atopic
      dermatitis). In this study we present in vitro Fourier transform Raman spectra of
      the stratum corneum from healthy skin, as well as from clinically undiseased skin
      of the right heel of atopic and psoriatic volunteers. Differences in the averaged
      spectra were detected, particularly in the spectral ranges of 1112-1142 (lipid
      band), 1185-1220, and 1394-1429 cm(-1). By using the first derivative of the
      averaged spectra and/or a statistical evaluation of the spectroscopic data it was
      possible to distinguish the skin types examined.

PMID- 11343283
TI  - Comparison of nitrophenylethyl and hydroxyphenacyl caging groups.
AB  - Nitrophenylethyl (NPE)- and hydroxyphenacyl (HPA)-caged nucleotides were employed
      in a time-resolved Fourier transform IR spectroscopy study on Ras-catalyzed
      guanosine triphosphate (GTP) hydrolysis. A fast kinetic component was observed
      following the photolysis of NPE-caged nucleotides in the NPE-GTP-Ras complex.
      However, this kinetic component was not observed in the HPA-GTP-Ras experiment.
      This fast kinetic component was likely due to a chemical reaction between Ras and
      the detached caging group, nitrosoacetophenone. This communication serves as a
      note of caution in interpreting spectral changes and kinetic behavior of the
      enzymatic systems employing NPE-caged compounds.

PMID- 11343284
TI  - Raman spectroscopy of secondary structure of elastinlike polymer poly(GVGVP).
AB  - Raman spectra of the elastinlike polypentapeptide poly(GVGVP) were measured in
      H(2)O and D(2)O as solutions and, after increasing the temperature, as
      suspensions and sediments. In addition, spectra of the polypentapeptide in the
      solutions of increasing concentration and in the solid state were also
      investigated by gradually evaporating the water. Significant changes in band
      frequencies, intensities, and shapes were found for selected Raman bands in the
      measured spectra, particularly for the C-H stretching, the glycine CH(2) wagging,
      and some amide vibrations. The C-H stretching vibrations are influenced
      predominantly by the presence of water, the glycine CH(2) wagging vibrations are
      associated with conformational transitions. Three possible types of poly(GVGVP)s
      in the presence of water were indicated: polymer chains in a relatively extended
      state in the solution, a beta-spiral structure in the suspension, and irregularly
      bent chains in the sediment.

PMID- 11343285
TI  - Assignment of the 1511 cm(-1) UV resonance Raman marker band of hemoglobin to
      tryptophan.
AB  - New UV resonance Raman (UVRR) data provide convincing evidence that a
      characteristic 1511 cm(-1) band in the T - R difference spectra of hemoglobin is
      due to the overtone of the Trp W18 fundamental at 756 cm(-1). Measured isotope
      shifts for 2-H and 15-N substitution at the indole NH group are twice as large
      for the 1511 cm(-1) band as for W18, and the 1511 cm(-1) intensity scales with
      that of W18 in the difference spectrum. Moreover, the UVRR excitation profile of
      the 1511 cm(-1) band tracks that of another tryptophan band, W16. Both are
      redshifted in hemoglobin, relative to aqueous tryptophan, reflecting H bonding
      within a hydrophobic environment in the protein. The 2xW18 assignment had been
      thrown into question by the observation of remnant 1511 cm(-1) intensity in the T
      - R spectra of hemoglobin labeled with tryptophan-d(5), a substitution that
      shifts W18 over 50 cm(-1). However, reexamination of the data suggests that this
      remnant intensity may result from a subtraction artifact arising from the
      downshift of another difference band, W3, from 1549 cm(-1) in unlabeled protein
      to 1522 cm(-1) in labeled protein. Restoration of the 2xW18 assignment
      establishes that the 1511 cm(-1) difference band, which is a useful indicator of
      the extent of T-state formation in hemoglobin, arises from the same residue,
      Trpbeta37, that gives rise to essentially all of the T - R signal from
      tryptophan.

PMID- 11343286
TI  - Antioxidant activity of 4-flavonil-1,4-dihydropyridine derivatives.
AB  - The effect of 4-flavonil-1,4-dihydropyridine derivatives on a chemical system
      involving a superoxide radical anion was tested using the chemiluminescence and
      spectrophotometry methods. All tested compounds enhanced the light emission from
      the system. The obtained results indicated that the tested derivatives may
      catalyze the conversion of superoxide radicals, thus showing superoxide dismutase
      activity.

PMID- 11343287
TI  - Temperature dependence of near-IR excited Raman spectra of crystalline hen egg
      white lysozyme.
AB  - Near-IR excited Raman spectroscopy was applied to examine the structural change
      of hen egg-white lysozyme in tetragonal crystals at low temperatures. There was
      little difference found in the amide I and amide III regions between the spectra
      observed at 77 and 298 K, suggesting that the secondary structures of lysozyme
      were conserved in the temperature range from 77 to 298 K. Several bands arising
      from the protein side chains, particularly the methylene and phenylalanyl groups,
      showed significant changes in either intensity or bandwidth (or in both of them)
      on going from 77 to 298 K. Some of the spectral changes occurred gradually over
      the wide temperature range, and others occurred abruptly at around 200-240 K. The
      implications of these findings are discussed.

PMID- 11343288
TI  - 7Li-NMR and FTIR studies of lithium, potassium, rubidium, and cesium complexes
      with ionophore lasalocid in solution.
AB  - Lasalocid metal salts were combined with 1 : 1 lithium and 2:2 potassium,
      rubidium, and cesium to form complexes. The nature of the lasolocid salt
      complexes was studied in a solid and chloroform by FTIR spectroscopy in the
      middle and far IR regions. The process of the complexation of lithium was also
      studied by (7)Li-NMR. In chloroform a 1 : 1 complex of lasalocid and Li(+) ions
      was formed. Continuous absorption was observed in the far FTIR spectrum of this
      complex. It indicated large Li(+) polarizability, which was due to fast
      fluctuations of the Li(+) ions in the multiminima potentials, in the monomeric
      structure. In the lasalocid salt with the other monovalent cations (K(+), Rb(+),
      Cs(+)) 2:2 complexes were formed in which the cations showed cation
      polarizability, which strongly depended on the mass and the radius of the
      cations.

PMID- 11343289
TI  - Layer V in cat primary auditory cortex (AI): cellular architecture and
      identification of projection neurons.
AB  - The cytoarchitectonic organization and the structure of layer V neuronal
      populations in cat primary auditory cortex (AI) were analyzed in Golgi, Nissl,
      immunocytochemical, and plastic-embedded preparations from mature specimens. The
      major cell types were characterized as a prelude to identifying their connections
      with the thalamus, midbrain, and cerebral cortex using axoplasmic transport
      methods. The goal was to describe the structure and connections of layer V
      neurons more fully. Layer V has three sublayers based on the types of neuron and
      their sublaminar projections. Four types of pyramidal and three kinds of
      nonpyramidal cells were present. Classic pyramidal cells had a long apical
      dendrite, robust basal arbors, and an axon with both local and corticofugal
      projections. Only the largest pyramidal cell apical dendrites reached the
      supragranular layers, and their somata were found mainly in layer Vb. Three types
      departed from the classic pattern; these were the star, fusiform, and inverted
      pyramidal neurons. Nonpyramidal cells ranged from large multipolar neurons with
      radiating dendrites, to Martinotti cells, with smooth dendrites and a primary
      trunk oriented toward the white matter. Many nonpyramidal cells were multipolar,
      of which three subtypes (large, medium, and small) were identified; bipolar and
      other types also were seen. Their axons formed local projections within layer V,
      often near pyramidal neurons. Several features distinguish layer V from other
      layers in AI. The largest pyramidal neurons were in layer V. Layer V neuronal
      diversity aligns it with layer VI (Prieto and Winer [1999] J. Comp. Neurol.
      404:332--358), and it is consistent with the many connectional systems in layer
      V, each of which has specific sublaminar and neuronal origins. The infragranular
      layers are the source for several parallel descending systems. There were
      significant differences in somatic size among these projection neurons. This
      finding implies that diverse corticofugal roles in sensorimotor processing may
      require a correspondingly wide range of neuronal architecture.

PMID- 11343291
TI  - Ultrastructure of the taste buds in the blind cave fish Astyanax jordani
      ("Anoptichthys") and the sighted river fish Astyanax mexicanus (Teleostei,
      Characidae).
AB  - This study describes the ultrastructure of the taste buds of the sighted river
      fish Astyanax mexicanus and of the blind cave fish Astyanax jordani (=
      Anoptichthys) (Teleostei, Characiformes, Characidae). In Astyanax and
      Anoptichthys, taste buds occur in the epithelia of the lips, oral cavity, and, in
      Anoptichthys, lower jaw. Both possess three types of taste buds: type I
      (elevated), type II (slightly elevated), and type III taste buds (not elevated or
      sunken). The taste buds are up to 60 microm high and up to 35 microm wide. The
      taste bud's sensory epithelium consists of 100--130 elongated cells: light cells,
      dense-cored-vesicles (dcv) -cells, dark cells, and degenerating cells. The dcv
      cells are rich in dense-cored vesicles and are described for the first time in a
      teleostean taste bud. At the taste bud's base, there lie two to three basal
      cells. The basal cells of type I and type II taste buds have microvillus (spine)
      like processes, in contrast to those of type III taste buds. The taste bud's
      nerve fiber plexus is situated between the bases of the elongated taste bud cells
      and the basal cells. Afferent synapses occur between dcv-cells and basal cells
      (presynaptic sides) and axons (postsynaptic side). Indistinct synapses occur
      between light cells and dark cells (presynaptic sides) and axons (postsynaptic
      side). The nerve fiber plexes of Anoptichthys type II and type III taste buds
      contain significantly more axon profiles than those of Astyanax. This may be
      associated with a compensatory improvement of the sense of taste in the blind,
      cave-dwelling fish.

PMID- 11343290
TI  - Plasticity of neurohypophysial terminals with increased hormonal release during
      dehydration: ultrastructural and biochemical analyses.
AB  - Arginine vasopressin- (AVP) and oxytocin- (OXT) secreting magnocellular neurons
      undergo gross structural changes with chronic physiological stimulation. Here, we
      investigated subcellular aspects of plasticity in rat neurohypophysial terminals
      during dehydration. Ultrastructural analyses demonstrated that chronic
      dehydration by 2% NaCl drinking for 7 days significantly decreased the numbers of
      neurosecretory granules and microvesicles but not the numbers of mitochondria.
      Moreover, in dehydrated rats, terminals making neurovascular contacts enlarged,
      whereas terminals in apposition to astrocytes, i.e., neuroglial contacts, became
      smaller. Western blot analyses demonstrated significant decreases in the levels
      of F3 and Thy-1 together with those of AVP- and OXT-neurophysin, but the levels
      of synaptophysin, SNAP-25, and GAP-43 were unchanged. Both F3 and Thy-1 were
      recovered in the buffer-insoluble pellet, and phosphatidyl inositol-specific
      phospholipase C treatment released both molecules from the crude membrane
      fraction, indicating that they are attached to terminal membranes by
      glycosylphosphatidyl inositol anchors. Confocal microscopic observations
      demonstrated that F3 colocalized with Thy-1 in the same terminals of
      magnocellular neurons. In contrast, the level of calretinin, a Ca(2+) binding
      protein was significantly increased with chronic dehydration. Thus, the present
      results suggest that enhancement of neurovascular contacts results from
      rearrangement of terminal-astrocyte and terminal-vessel contacts rather than
      enlargement or sprouting of magnocellular terminals themselves. The down
      regulation of F3 and Thy-1 may contribute to enhancement of neurovascular
      contacts that accompany increased peptide release during dehydration.

PMID- 11343292
TI  - Muscarinic m1 and m2 receptor proteins in local circuit and projection neurons of
      the primate striatum: anatomical evidence for cholinergic modulation of
      glutamatergic prefronto-striatal pathways.
AB  - The cellular and subcellular localization of muscarinic receptor proteins m1 and
      m2 was examined in the neostriatum of macaque monkeys by using light and electron
      microscopic immunocytochemical techniques. Double-labeling immunocytochemistry
      revealed m1 receptors in calbindin-D28k--positive medium spiny projection
      neurons. Muscarinic m1 labeling was dramatically more intense in the striatal
      matrix compartment in juvenile monkeys but more intense in striosomes in the
      adult caudate, suggesting that m1 expression undergoes a developmental age
      dependent change. Ultrastructurally, m1 receptors were predominantly localized in
      asymmetric synapse-forming spines, indicating that these spines receive
      extrastriatal excitatory afferents. The association of m1-positive spines with
      lesion-induced degenerating prefronto-striatal axon terminals demonstrated that
      these afferents originate in part from the prefrontal cortex. The synaptic
      localization of m1 in these spines indicates a role of m1 in the modulation of
      excitatory neurotransmission. To a lesser extent, m1 was present in symmetric
      synapses, where it may also modulate inhibitory neurotransmission originating
      from local striatal neurons or the substantia nigra. Conversely, m2/choline
      acetyltransferase (ChAT) double labeling revealed that m2-positive neurons
      corresponded to large aspiny cholinergic interneurons and ultrastructurally, that
      the majority of m2 labeled axons formed symmetric synapses. The remarkable
      segregation of the m1 and m2 receptor proteins to projection and local circuit
      neurons suggests a functional segregation of m1 and m2 mediated cholinergic
      actions in the striatum: m1 receptors modulate extrinsic glutamatergic and
      monoaminergic afferents and intrinsic GABAergic afferents onto projection
      neurons, whereas m2 receptors regulate acetylcholine release from axons of
      cholinergic interneurons.

PMID- 11343293
TI  - Regulation of the gene encoding the monocyte chemoattractant protein 1 (MCP-1) in
      the mouse and rat brain in response to circulating LPS and proinflammatory
      cytokines.
AB  - Accumulating evidence supports the existence of an innate immune response in the
      brain during systemic inflammation that is associated with a robust induction of
      proinflammatory cytokines and chemokines by specific cells of the central nervous
      system. The present study investigated the genetic regulation and fine cellular
      distribution of the monocyte chemoattractant protein-1 (MCP-1) in the brain of
      mice and rats in response to systemic immune insults. MCP-1 belongs to a
      superfamily of chemokines that have a leading role in the early chemotaxic events
      during inflammation. In situ hybridization histochemistry failed to detect
      constitutive expression of the chemokine transcript in the cerebral tissue except
      for the area postrema (AP) that exhibited a low signal under basal conditions.
      This contrasts with the strong and transient induction of the mRNA encoding MCP-1
      following a single systemic bolus of lipopolysaccharide (LPS), recombinant
      interleukin-1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF-alpha). These
      stimuli rapidly triggered (30 to 90 minutes) MCP-1 transcription in all the
      circumventricular organs (CVOs), the choroid plexus (chp), the leptomeninges, and
      along the cerebral blood vessels. The time-related induction and intensity of the
      signal differed among the challenges, route of administration and species, but
      MCP-1-expressing cells were always found in vascular-associated structures and
      those devoid of blood-brain barrier. At later times, few isolated microglia
      across the brain parenchyma depicted positive signal for MCP-1 mRNA. A dual
      labeling procedure also provided convincing anatomical evidence that endothelial
      cells of the microvasculature and a few myeloid cells of the CVOs and chp were
      positive for the transcript during endotoxemia. This gene is under a
      sophisticated transcriptional regulation, as the hybridization signal returned to
      undetectable levels 12 to 24 hours after all the treatments in both species. Of
      interest are the data that only ligands that triggered nuclear factor kappa B (NF
      kappa B) signaling had the ability to increase MCP-1 gene expression, because
      high doses of IL-6 remained without effects. These data provide the anatomical
      evidence that MCP-1 is expressed within specific populations of cells in response
      to systemic inflammatory molecules that use NF-kappa B as intracellular signaling
      system. This chemokine may therefore play a critical role in the cerebral innate
      immune response and contribute to the early chemotaxic events during chronic
      cerebral inflammation.

PMID- 11343295
TI  - New heads for Freud's hydra: psychoanalysis in Los Angeles.
AB  - This paper describes the transplantation of psychoanalysis from Europe to Los
      Angeles and the similarities and differences in followers, cultural attitudes,
      institutional organization, and patient symptoms. Psychoanalysis in both places
      attracted psychiatrists, psychologists, social workers, artists, writers, and
      movie people, all committed to "modernism" and cultural change. But special
      American conditions created greater institutional rigidity, medicalization, and a
      more diffuse patient symptomatology centered on the maternal relationship. Such
      conditions also fostered bitter disputes over modifications of psychoanalytic
      theory and practice which have only recently become less acute as the status of
      psychoanalysis has declined in America.

PMID- 11343296
TI  - Thinking through war: the social thought of Richard T. Ely, John R. Commons, and
      Edward A. Ross during the First World War.
AB  - This paper examines the social thought of University of Wisconsin professors
      Richard T. Ely, John R. Commons, and Edward A. Ross during World War I. Like many
      of their fellow scholars, these three were actively involved in the pro-war
      effort. Although their support for the war was strongly conditioned by personal
      and occupational considerations, the impact of their wartime service was not
      restricted to those realms. Their social thought, which they impressed into
      service explaining and justifying the war, was itself altered in subtle and
      sometimes surprising ways by the forceful positions they took on the political,
      economic, and racial significance of the conflict.

PMID- 11343297
TI  - Introducing psychology as an academic discipline in France: Theodule Ribot and
      the College de France (1888-1901).
AB  - This paper describes the context in which the teaching of psychology as an
      autonomous discipline was introduced in France, and reproduces the first
      psychology lecture given in France by Theodule Ribot on 9 April 1888 at The
      College de France. In France, this recognition was delayed because of the
      negative influence of spiritualist philosophy. It took both the acknowledged
      status of a man (Ribot) and a minister's decision for this new type of teaching
      to be accepted in France. After describing the events that took place at the
      College de France and at the Academy of Moral and Political Sciences, we
      reproduce in full Ribot's inaugural lecture at the College, an important document
      for the history of French psychology. We conclude by describing the circumstances
      in which this teaching came to its end in 1901.

PMID- 11343300
TI  - Holoprosencephaly associated with an apparent isolated 2q37.1-->2q37.3 deletion.
AB  - A female infant survived 5(1/2) hours after delivery at 33 weeks gestation.
      Autopsy showed a lobar variant of holoprosencephaly (HPE). Cytogenetic analysis
      revealed a 2q37.1-->2q37.3 deletion. This case represents the fourth reported
      case of HPE associated with partial monosomy 2q37 and the first with an apparent
      isolated 2q37 deletion. Chromosome segment 2q37.1-->2q37.3 may harbor yet another
      locus important in forebrain development, which, when disrupted, can lead to
      brain malformations within the HPE spectrum.

PMID- 11343301
TI  - Human twinning is not linked to the region of chromosome 4 syntenic with the
      sheep twinning gene FecB.
AB  - The tendency to dizygotic (DZ) twinning is inherited in both humans and sheep,
      and a fecundity gene in sheep (FecB) maps to sheep chromosome 6, syntenic with
      human 4q21-25. Our aim was to see whether a gene predisposing to human DZ
      twinning mapped to this region. DNA was collected from 169 pairs and 17 sets of 3
      sisters (trios) from Australia and New Zealand who had each had spontaneous DZ
      twins, mostly before the age of 35, and from a replication sample of 111 families
      (92 affected sister pairs) from The Netherlands. Exclusion mapping was carried
      out after typing 26 markers on chromosome 4, of which 8 spanned the region likely
      to contain the human homologue of the sheep FecB gene. We used nonparametric
      affected sib pair methods for linkage analysis [ASPEX 2.2, Hinds and Risch,
      1999]. Complete exclusion of linkage (lod < -2) of a gene conferring a relative
      risk for sibs as low as 1.5 (lambda(s) > 1.5) was obtained for all but the p
      terminus region on chromosome 4. Exclusion in the syntenic region was stronger,
      down to lambda(s) = 1.3. We concluded that if there is a gene influencing DZ
      twinning on chromosome 4, its effect must be minor.

PMID- 11343302
TI  - Axenfeld-Rieger anomaly, hypertelorism, clinodactyly, and cardiac anomalies in
      sibs with an unbalanced translocation der(6)t(6;8).
AB  - We describe two sibs with the unbalanced translocation
      der(6)t(6;8)(p25.1;q24.23), making them monosomic for 6p25.1-->6pter and trisomic
      for 8q24.23-->8qter. The siblings both possess Axenfeld-Rieger Anomaly (ARA),
      hypertelorism, clinodactyly, and cardiac anomalies, but otherwise vary in the
      phenotypic manifestations of this unbalanced translocation. We compare them to
      previously described cases and a recently proposed syndrome of ARA, atrial septal
      defect, and sensorineural deafness.

PMID- 11343303
TI  - Mutations in the EDA gene in three unrelated families reveal no apparent
      correlation between phenotype and genotype in the patients with an X-linked
      anhidrotic ectodermal dysplasia.
AB  - Anhidrotic ectodermal dysplasia (EDA) is caused by mutations in the EDA gene
      encoding ectodysplasin A, a member of the TNF ligand superfamily involved in the
      communication between the cells. The structure of the EDA gene was investigated
      in three patients exhibiting clinical symptoms of EDA in an attempt to correlate
      the molecular findings with the phenotype of the patients. Genomic DNA was
      analyzed by single stranded conformation polymorphism (SSCP) followed by direct
      sequencing. In one of the patients, as well as in his heterozygous mother and
      sister, a single T insertion was evidenced in exon 3 between nucleotides 713 and
      714 that changed Lys codon (AAA) into a termination codon TAA (Lys158Ter). In the
      other patient, A1321T transversion was demonstrated. The same mutation was found
      in his heterozygous mother and resulted in a change of Ileu360Asn that might
      generate an additional glycosylation site. In the third patient an A1285G
      transition was revealed. This mutation that originated de novo was localized in a
      region that is highly conserved in TNF ligand family and caused substitution of
      Ala349Thr. Localization of the mutations in the extracellular domain of
      ectodysplasin A suggested that the primary cause of EDA is a defect in
      communication between the cells responsible for the development of skin
      appendages. Despite a different character and localization of the mutations, no
      apparent correlation between phenotype and genotype of the patients was
      evidenced. Some differences in the patients' phenotype were observed.

PMID- 11343304
TI  - Progressive erosive arthropathy with contractures, multicentric osteolysis-like
      changes, characteristic craniofacial appearance, and dermatological
      abnormalities: a new syndrome?
AB  - We report a 27-year-old man with an apparently new syndromic form of progressive
      erosive arthropathy and contractures of small and large joints associated with
      mild epiphyseal changes, normal vertebrae, and generalized osteopenia. The
      patient had a characteristic craniofacial appearance, dermatological
      abnormalities, and normal intelligence. The head was large with frontal bossing.
      The face was elongated with malar hypoplasia, thin upper lip, prominent lower
      jaw, high arched palate, dental malocclusion, and prominent ears with absent ear
      lobules. Dermatological abnormalities included malar erythema and facial
      telangiectasia together with multiple nevi and lentigenes all over the body.
      Pseudorheumatoid arthropathy, spondyloarthropathy, and Borrone
      dermatocardioskeletal syndrome were considered in the differential diagnosis and
      were excluded. Also, no similar cases have been found in POSSUM or the London
      Dysmorphology databases.

PMID- 11343305
TI  - Disposition of homocysteine in subjects heterozygous for homocystinuria due to
      cystathionine beta-synthase deficiency: relationship between genotype and
      phenotype.
AB  - We have investigated 31 subjects from five unrelated families with one or more
      members with cystathionine beta-synthase (CBS) deficiency. On the basis of their
      CBS genotype, the subjects were grouped as normal (n = 11) or heterozygotes (n =
      20). Based on pyridoxine effect in the probands, the heterozygotes were further
      classified as pyridoxine-responsive (n = 9) or non-responsive (n = 11).
      Heterozygous subjects had normal fasting total plasma homocysteine (tHcy), but
      median urinary tHcy excretion rate was significantly elevated compared to healthy
      controls (0.39 micromol/h vs 0.24 micromol/h, P < 0.05). An abnormal tHcy
      response after methionine loading identified 73% of the pyridoxine non-responsive
      heterozygotes, but only 33% of the pyridoxine responsive participants. The
      increase in cystathionine or the change in tHcy relative to cystathionine did not
      improve diagnostic accuracy of the methionine loading test. After Hcy loading,
      the maximal increase in tHcy was significantly elevated, whereas t(1/2) was
      normal in heterozygotes. In conclusion, a single biochemical test cannot
      discriminate CBS heterozygotes from controls. Abnormal tHcy response after
      methionine loading was the most sensitive test. Our data suggest that the urinary
      tHcy excretion rate is a simple, non-invasive approach for studying mild
      disturbances in Hcy metabolism.

PMID- 11343306
TI  - Fontaine-Farriaux craniosynostosis: second report in the literature.
AB  - Craniosynostosis is determined by the precocious fusion of one or more calvarial
      sutures leading to an abnormal skull shape. Additionally, nodular heterotopia is
      a disorder of neuronal migration and/or proliferation. We describe a very rare
      multiple congenital anomalies (MCA) syndrome in which craniosynostosis is
      associated with bilateral periventricular nodular heterotopia (BPNH) of the gray
      matter and other malformations involving hands, feet, and the gut. Clinical
      findings and further investigations suggest the diagnosis of craniosynostosis
      Fontaine-Farriaux type. To the best of our knowledge, this case is only the
      second report of this MCA syndrome. Based on the clinical and radiological data
      of the two cases reported, we hypothesize that this malformative complex may be
      considered a new BPNH/MCA syndrome and propose to classify it as
      BPNH/craniosynostosis. Previous studies demonstrated that at least two BPNH/MCA
      syndromes have been mapped to the Xq28 chromosomal region in which a causative
      gene for isolated BPNH is located. The same authors hypothesized that other BPNH
      syndromes could be due to microrearrangements at the same Xq28 region. Our case
      presents several overlapping features with some BPNH/MCA syndromes and it is
      possible that this new complex disorder may be caused by rearrangements at the
      same chromosomal region that could alter expression of different genes in Xq28.

PMID- 11343307
TI  - mtDNA analysis of Leber hereditary optic neuropathy associated with
      spondyloepiphyseal dysplasia.
AB  - A patient was diagnosed in 1974 with the unique combination of Leber hereditary
      optic neuropathy (LHON) and spondyloepiphyseal dysplasia. The entire
      mitochondrial DNA (mtDNA) sequence from this patient was determined in order to
      identify candidate pathogenic mutations. The patient's mtDNA carried the LHON
      mutation at nucleotide 14484, thus elucidating the etiology of his optic
      neuropathy. We also identified another ND6 mutation at nucleotide 14420. This
      latter mutation is probably a clinically benign private polymorphism, although a
      pathogenic role in his skeletal abnormalities or in his optic neuropathy cannot
      yet be ruled out.

PMID- 11343308
TI  - Mutation and haplotype analyses in 26 Spanish Sanfilippo syndrome type A
      patients: possible single origin for 1091delC mutation.
AB  - Mucopolysaccharidosis IIIA, also known as Sanfilippo syndrome type A, is an
      autosomal recessive storage disorder caused by deficiency of sulfamidase. The
      disease results in severe central nervous system degeneration often with mild
      somatic features that may delay the clinical diagnosis. Molecular analyses would
      allow early and unequivocal heterozygote detection, providing a useful tool for
      genetic counselling. About 40 mutations have been reported in the sulfamidase
      gene, with a very uneven distribution in different patient populations. We have
      previously described the high prevalence of mutation 1091delC in a small number
      of Spanish Sanfilippo A patients. The aim of the present work is to extend the
      mutational study to a total of 26 unrelated patients and perform haplotype
      analysis in order to study the origin of some mutations. The whole coding region
      of the gene was scanned by SSCP analysis and sequencing. This allowed the
      identification of 14 different mutations, corresponding to 90% of the mutant
      alleles. Seven of these mutations were only found in this Spanish group of
      patients, three of which, R150W, R433Q and R433W, are described here for the
      first time. We have also analyzed four internal polymorphisms and constructed the
      corresponding haplotypes. Chromosomes bearing mutation 1091delC show a conserved
      haplotype suggesting a common origin for this mutation. Moreover, all other
      mutations found twice or more also have conserved haplotypes for those
      polymorphic markers.

PMID- 11343309
TI  - Genetic segregation analysis of autonomic nervous system dysfunction in families
      of probands with idiopathic congenital central hypoventilation syndrome.
AB  - Idiopathic congenital central hypoventilation syndrome (CCHS) is a very rare
      syndrome with major respiratory complications. Hypothesizing that CCHS is the
      most severe manifestation of general autonomic nervous system dysfunction (ANSD),
      we applied a case-control family study design to investigate the genetics of
      ANSD. Fifty-two probands with CCHS were identified, as well as 52 age-, race-,
      and gender-matched controls. ANSD phenotypic features were characterized in the
      cases, controls, and their family members. Our earlier studies found that most
      ANSD symptoms were more likely in CCHS cases and their relatives than in controls
      and their relatives (P < 0.05). The goal of the current study was to determine if
      the familiality of ANSD was consistent with a genetic pattern. We performed major
      locus segregation analysis of ANSD utilizing regressive models. CCHS probands
      were assumed to be affected; controls and relatives were designated as affected
      if they had two or more relevant symptoms. The hypothesis of "no transmission and
      no familial effects" was rejected in both case and control families. Case
      families were consistent with transmission of a major effect; control families
      were not (the difference in the pattern of results was significant, P < 0.0001).
      In the total data set, the best-fitting model was codominant Mendelian
      inheritance of a major gene for ANSD. These case-control family studies support
      our hypothesis that CCHS is the most severe manifestation of a general ANSD, with
      a family pattern consistent with Mendelian transmission, and demonstrate the
      potential utility of the approach to studies of other, similarly intractable
      disorders.

PMID- 11343310
TI  - Case/control family study of autonomic nervous system dysfunction in idiopathic
      congenital central hypoventilation syndrome.
AB  - Children with idiopathic congenital central hypoventilation syndrome (CCHS) have
      a complex phenotype consistent with an imbalance of the autonomic nervous system
      (ANS). Since CCHS may be genetic in origin, we hypothesized that relatives of
      individuals with CCHS may exhibit symptoms of ANS dysfunction (ANSD), albeit in a
      milder form. We tested this hypothesis by assessing aspects of ANS function in
      relatives of CCHS cases vs. relatives of matched controls with a scripted
      questionnaire. Only those 35 symptoms of ANSD exhibited by > or =5% of the CCHS
      cases were included in the analysis as the basis for determining ANSD affection
      status. Two different arbitrary ANSD affection status definitions are presented
      in detail: any case, control, or relative with positive findings (1) in two or
      more symptoms, or (2) in two or more systems. The subjects included in the
      analysis totaled 2,353, including 56 CCHS cases, 56 age-, gender-, and race
      matched controls, and their families. Under each of the two arbitrary ANSD
      affection statuses, CCHS cases and parents of cases were more likely to be
      affected than controls and parents of controls (P < 0.001 for both comparisons),
      16% of the CCHS siblings had the ANSD phenotype with two or more symptoms,
      compared to 4% of control siblings (P = 0.03). Aunts and uncles of the CCHS cases
      were also significantly more likely to have two or more ANSD symptoms than were
      aunts and uncles of the controls (P= 0.009). These results support our hypothesis
      and also indicate that relatives of the CCHS cases tended to manifest a milder
      spectrum of ANSD, with fewer systems and/or fewer symptoms than the cases.

PMID- 11343311
TI  - Prenatal diagnosis and molecular cytogenetics in a case of partial trisomy 14 and
      monosomy 21.
AB  - We report an unbalanced translocation involving chromosomes 14 and 21 which
      presented as fetal ventriculomegaly at 33 weeks gestation. Second trimester
      ultrasound had indicated normal fetal anatomy, including normal intracranial
      structures. Parental karyotypes showed a paternal balanced translocation:
      46,XY,t(14;21)(q12;q21). The unbalanced translocation in the fetus resulted in
      trisomy for 14pter-->q12 and monosomy for 21pter-->q21. Postnatal examination
      showed that the male infant had a cleft palate, but no cleft lip, and mild
      dysmorphic features. Postnatal MRI revealed bilateral and symmetric dilatation of
      the occipital horns, atria, and temporal horns of the lateral ventricles.
      Molecular cytogenetic techniques were used to delineate further the breakpoint on
      chromosome 14 to a site distal of the D14S1071 locus and the breakpoint on
      chromosome 21 to a region between D21S1918 and D21S1902. More precise definitions
      of chromosomal breakpoints in such clinical cases should provide more accurate
      prognosis for individuals with unbalanced karyotypes and assist in the
      identification of putative developmentally important genes.

PMID- 11343312
TI  - Biliary atresia and Kabuki syndrome: another case with long-term follow-up.

PMID- 11343313
TI  - High frequency of the N34S mutation in the SPINK1 gene in chronic pancreatitis
      detected by a new PCR-RFLP assay.

PMID- 11343314
TI  - Professor G. Roberto Burgio: a man for all seasons.

PMID- 11343315
TI  - Practicing a culture of pediatric immunogenetics.

PMID- 11343316
TI  - Proximal trisomy of 1q mosaicism in a girl with hypertrophic cardiomyopathy
      associated with Wolff-Parkinson-White syndrome and multiple congenital anomalies.
AB  - We report an African American female who is mosaic for partial trisomy of 1q due
      to a direct duplication of 1q12 to 1q25. The child has hypertrophic
      cardiomyopathy with Wolff-Parkinson-White syndrome. The physical features include
      micrognathia, cleft palate, low set ears, posteriorly placed thumbs, and
      syndactyly of the second and third toes of both feet. Other abnormalities include
      intestinal malrotation, scoliosis, mental retardation, cerebral palsy, and
      hydrocephalus. There was also a selective deficiency of antibody responses to
      polysaccharide antigens. Proximal duplication of chromosome 1q is rare and has
      not been previously associated with hypertrophic cardiomyopathy. Most known gene
      disorders related to hypertrophic cardiomyopathy are autosomal dominant missense
      mutations in sarcomeric protein genes; however, none of the sarcomeric genes
      previously linked to hypertrophic cardiomyopathy are in this region. This finding
      thus highlights the possibility of additional genetic mechanisms for hypertrophic
      cardiomyopathy.

PMID- 11343317
TI  - Congenital heart defects in Kabuki syndrome.
AB  - Kabuki makeup (Niikawa-Kuroki) syndrome (KS) is characterized by distinct facial
      anomalies, mental retardation, congenital heart defect (CHD), and skeletal
      malformations. In the present study we analyze cardiac characteristics and
      differences in sex prevalence of specific CHDs in our series of patients with KS
      and review published reports from the literature. Between January 1992 and
      February 2000, 60 patients (37 males and 23 females) with KS underwent phenotypic
      and cardiac evaluations at our hospital. CHD was diagnosed in 35 (58%) of our
      patients. Aortic coarctation (COA) (23%), atrial septal defect (ASD) (20%), and
      ventricular septal defect (VSD) (17%) were the most frequent CHDs in our series
      and in previous reports from the literature. Male preponderance was noted in
      patients with COA. In conclusion, CHD is a cardinal feature of KS. There is an
      overlap between cardiac malformations of KS and those of Turner syndrome. Male
      preponderance in patients with KS and COA supports the hypothesis that genes
      located on the X chromosome may be involved in determining KS in some patients.
      The high prevalence of CHD prompts accurate re-examination of patients evaluated
      by pediatric cardiologists in order to identify mild and still unrecognized cases
      of KS.

PMID- 11343318
TI  - Segregation analysis of Scheuermann disease in ninety families from Siberia.
AB  - Scheuermann disease [OMIM number 181440] is the most common cause of structural
      kyphosis in adolescence. Segregation analysis using a model with gender effects
      was applied to 90 pedigrees from Barnaul (West Siberia, Russia) ascertained
      through a proband with Scheuermann disease. The transmission probability model
      was used to detect major gene effect. A significant contribution of a major gene
      to the control of the pathology was established. Inheritance of the disease can
      be described within the framework of a dominant major gene diallele model.
      According to this model, Scheuermann disease should never occur in the absence of
      the mutant allele. All male carriers of the mutant allele develop the disease,
      while only a half of female carriers manifest it. We found a high frequency of
      idiopathic scoliosis in the families with Scheuermann disease (0.08 vs. 0.01-0.02
      in general population). We also observed a succession of idiopathic scoliosis and
      Scheuermann disease in consecutive generations. The familial aggregation of these
      two spinal pathologies in the present sample may indicate a genetic unity of
      Scheuermann disease and idiopathic scoliosis.

PMID- 11343319
TI  - Excess paternal age in apparently sporadic osteogenesis imperfecta.
AB  - The objective of this study was to examine whether parental age is associated
      with the occurrence of apparently sporadic osteogenesis imperfecta (OI). We
      compared parental age and the joint distribution of maternal and paternal age
      with expected distributions based on statutory birth records for each year and
      location of birth. The study included patients with OI based in the United
      Kingdom. The study was restricted to cases born in England, Wales, and Scotland
      between 1961 and 1998. Subgroup analysis was by clinical type [Sillence et al.,
      1979: J Med Genet 16:101-116] and apparent mode of inheritance based on pedigree
      analysis. Of 730 eligible cases, 357 were apparently sporadic. The mean age of
      fathers at birth of children with apparently sporadic OI was 0.87 years greater
      than expected (P = 0.010; 95% confidence interval = 0.21 to 1.54 years). The
      relative risk was 1.62 for fathers in the highest quintile of paternal age
      compared with fathers in the lowest quintile. The magnitude of the paternal age
      excess did not differ significantly between Sillence types (analysis of variance
      P = 0.534). In sporadic cases, paternal age was 0.51 years greater than expected,
      given maternal age, year, and location of birth (P = 0.033). In contrast, in
      familial cases, there was no significant paternal age excess, and paternal age
      was not significantly different from that expected given maternal age. Increased
      paternal age is a significant risk factor for sporadic OI. This effect is not
      accounted for by increasing maternal age. The magnitude of the paternal age
      excess is small in comparison with that in some other autosomal dominant
      disorders.

PMID- 11343320
TI  - Familial benign recurrent vertigo.
AB  - Benign recurrent vertigo (BRV) has been previously linked to migraine but there
      have been no prior studies of families with BRV. We studied the families of 24
      patients who presented to our clinic with BRV and who reported a family history
      of similar attacks of vertigo. All probands underwent diagnostic evaluation to
      exclude identifiable causes of recurrent vertigo and they completed a
      standardized medical questionnaire pertaining to episodic vertigo and the
      features of migraine. This questionnaire was also sent to all relatives of the
      probands who agreed to participate. Of 220 relatives who returned questionnaires,
      37% reported BRV and 50% met the diagnostic criteria for migraine. By contrast,
      only one of 43 (2%) unrelated spouses reported BRV and 10 of 43 (23%) met the
      diagnostic criteria for migraine. More than two-thirds of relatives with BRV met
      the diagnostic criteria for migraine and the majority reported that they had a
      typical migraine headache with at least some of their episodes of vertigo. Both
      BRV and migraine showed a female preponderance (more than 2 to 1). Familial BRV
      seems to be a migraine syndrome, probably inherited in an autosomal dominant
      fashion with decreased penetrance in men. In the search for the causative gene,
      vertigo may be a more useful marker than migraine because recurrent vertigo is
      relatively rare in the general population whereas migraine is very common.

PMID- 11343321
TI  - Hajdu--Cheney syndrome: evolution of phenotype and clinical problems.
AB  - Hajdu-Cheney syndrome is a rare, autosomal dominant disorder comprising
      acroosteolysis of the distal phalanges with associated digital abnormalities,
      distinctive craniofacial and skull changes, dental anomalies, and proportionate
      short stature. The clinical and radiologic characteristics of Hajdu-Cheney
      syndrome develop and progress with age. Many of the medical problems that arise
      in this syndrome cluster in specific age ranges. Case reports of six affected
      individuals in two additional families and a summary of the English literature is
      presented with emphasis on the changing physical findings and medical sequelae
      over time.

PMID- 11343322
TI  - Novel mutations and the emergence of a common mutation in the SDHD gene causing
      familial paraganglioma.
AB  - Familial paragangliomas (PGL) are slow-growing, highly vascular, generally benign
      neoplasms, usually of the head and neck, that arise from neural crest cells. This
      rare autosomal dominant disorder is highly penetrant and influenced by genomic
      imprinting through paternal transmission. Timely detection of these tumors may
      afford the affected individual the opportunity to avoid the potential serious
      morbidity associated with surgical removal and the mortality that may accompany
      local and distant metastases. Linkage to two distinct chromosomal loci, 11q13.1
      and 11q23, has been previously reported. Recently, germline mutations in SDHD, a
      mitochondrial complex II gene on chromosome 11q23, have been demonstrated. We
      evaluated members of seven families with PGL, five previously studied and shown
      to have linkage to chromosome 11q23. The entire coding region of the SDHD gene
      was sequenced and yielded four novel mutations and one mutation shared in three
      of our unrelated families. Novel mutations found included a truncating mutation
      in exon 2, as well as a missense mutation, a deletion, and an insertion in exon
      4. Three of our families had a common mutation in exon 3 (P81L) that has been
      reported and thought to be a founder mutation. A restriction enzyme assay was
      developed for initial screening of this mutation. Molecular analysis is now
      available and recommended for presymptomatic diagnosis in those at-risk
      individuals and for confirmatory diagnosis in those having PGL.

PMID- 11343324
TI  - Jackson-Weiss syndrome.

PMID- 11343323
TI  - Century of Jackson-Weiss syndrome: further definition of clinical and
      radiographic findings in "lost" descendants of the original kindred.
AB  - Jackson-Weiss syndrome (JWS) is a condition consisting of craniosynostosis
      characterized by premature fusion of the cranial sutures and/or characteristic
      radiographic anomalies of the feet. The condition is inherited as an autosomal
      dominant trait with high penetrance and variable expressivity. Six different
      mutations in the fibroblast growth factor receptor 2 have been identified in
      patients with the clinical diagnosis of JWS. Jabs et al. [1994: Nat Genet 8:275
      279] identified an Ala344Gly substitution in two branches of the family in which
      the clinical syndrome was originally described. This is the only publication to
      document this mutation in a family with the clinical diagnosis of JWS. In this
      study, we have identified a previously unrecognized branch of the original family
      with individuals that meet the clinical criteria for the diagnosis of JWS. We
      demonstrate that a mutation that produces the Ala344Gly substitution is present
      in affected members. This family illustrates the widely variable expression of
      the mutation, including a novel phenotype in the proband with a leg-length
      discrepancy and unilateral absence of the fifth digital ray in her right foot. We
      identify the clinical and detailed radiographic features of each affected
      individual and offer considerations when making the diagnosis of JWS.

PMID- 11343325
TI  - Burning down DEFECT11.

PMID- 11343327
TI  - Causes of premature death in Proteus syndrome.

PMID- 11343328
TI  - Impact of sulfonylurea receptor 1 genetic variability on non-insulin-dependent
      diabetes mellitus prevalence and treatment: a population study.
AB  - The high affinity sulfonylurea receptor 1 (SUR1) is involved in the metabolism of
      glucose in pancreatic beta-cells. We investigated the impact of the SUR1 intron
      16-3t-->c polymorphism on non-insulin-dependent diabetes mellitus (NIDDM)
      prevalence in a large representative sample of French men and women, 35-64 years
      old, and explored potential relationships between the SUR1 intron 16 -t-->c
      polymorphism and sulfonylurea therapy efficiency. This study took place in Lille
      (northern), Strasbourg (eastern), and Toulouse (southern France). One hundred and
      twenty-two subjects with NIDDM were registered. We stratified NIDDM subjects
      according to their medical treatment: sulfonylureas (n = 70) versus other
      treatments (n = 50). From the three populations, a control group was selected (n
      = 1,250). Subjects carrying the cc intron 16 genotype had an increased risk of
      NIDDM [odds ratio (OR) = 1.76, 95% confidence interval (CI) 1.10-2.80; P =
      0.017]. Subjects bearing at least one -3c allele and treated with sulfonylurea
      agents had fasting plasma triglyceride concentrations 35% lower than subjects
      that were tt homozygous (P = 0.026), whereas no difference could be detected
      between genotypes in NIDDM subjects treated with other treatments. The SUR1
      intron 16 -3t-->c polymorphism was associated with an increased susceptibility to
      NIDDM in this population study, and seems to modulate the sulfonylurea therapy
      efficiency on hypertriglyceridemia reduction. This observation may help to better
      target the various therapies available for treatment of NIDDM.

PMID- 11343329
TI  - Early-onset liver disease complicated with acute liver failure in Alstrom
      syndrome.
AB  - We report a case of Alstrom syndrome with evidence of extensive hepatic disease
      diagnosed at five years of age, who subsequently developed acute liver failure
      and died at eight years of age. Such a case, with the patient dying before the
      age of ten, has not been described before. The biochemical findings during our
      patient's liver failure raised the question of a possible mitochondrial function
      defect in this syndrome. Further investigation of this possibility is needed.

PMID- 11343330
TI  - Liver fibrocystic disease and polydactyly: proposal of a new syndrome.
AB  - Liver fibrocystic disease (LFCD), characterized by dilatation of the intrahepatic
      bile ducts and variable degree of fibrosis, can be present alone or as part of
      many syndromes, such as Bardet-Biedl syndrome (BBS), Meckel syndrome, Jeune
      asphyxiating thoracic dysplasia, and Fraser-Jequier-Chen syndrome. We report two
      cases of LFCD and polydactyly with features similar, but not diagnostic of, BBS.
      Patient 1 was an 18-month-old boy with mental retardation, polydactyly, chronic
      renal failure, convergent strabismus, and hepatic fibrosis. Patient 2 was a male
      neonate with LFCD and polydactyly. Their manifestations could not be diagnosed as
      any of the previous mentioned entities. Difficulties in the early diagnosis of
      BBS have been previously reported and this could explain the clinical variability
      and heterogeneity of manifestations at the time of diagnosis. On the other hand,
      the existence of liver abnormalities in association with BBS has been previously
      described, but is rare. Our patients' malformations might represent a new entity
      where autosomal recessive inheritance is probable, but other patterns cannot be
      ruled out.

PMID- 11343331
TI  - Type I diabetes mellitus in a patient with chromosome 22q11.2 deletion syndrome.
AB  - We describe a patient with type I diabetes, clinical findings consistent with
      velocardiofacial syndrome, and a chromosome 22q11.2 deletion. A nine-year-old boy
      presented with a history of polyuria, polydipsia, weight loss, hyperglycemia,
      ketosis, serum insulin antibodies, and a low C-peptide level. He had distinctive
      facial features, learning disabilities, short stature, and a history of glottic
      web and clubfoot. Although a normal karyotype was obtained, fluorescence in situ
      hybridization (FISH) revealed a submicroscopic deletion in the
      DiGeorge/velocardiofacial syndrome critical region at 22q11.2. His maternal half
      brother also carried a chromosome 22q11.2 deletion. His mother has similar facial
      features and hypoparathyroidism. Autoimmune problems associated with chromosome
      22q11.2 deletions have been reported. We suggest that the defects in immune
      regulation due to T-cell deficiency in chromosome 22q11.2 deletion syndrome may
      predispose to autoimmune disorders, including type I diabetes mellitus.

PMID- 11343332
TI  - Cytogenetic and molecular characterization of two isodicentric Y chromosomes.
AB  - We report the results of detailed molecular-cytogenetic studies of two
      isodicentric Y [idic(Y)] chromosomes identified in patients with complex mosaic
      karyotypes. We used fluorescence in situ hybridization (FISH) and polymerase
      chain reaction (PCR) to determine the structure and genetic content of the
      abnormal chromosomes. In the first patient, classical cytogenetics and FISH
      analysis with Y chromosome-specific probes showed in peripheral blood lymphocytes
      a karyotype with 4 cell lines:
      45,X[128]/46,X,+idic(Y)(p11.32)[65]/47,XY,+idic(Y)(p11.32)[2]/47,X,+2idic(Y)(p11.
      2)[1]. No Y chromosome material was found in the removed gonads. For precise
      characterization of the Yp breakpoint, FISH and fiberFISH analysis, using a
      telomeric probe and a panel of cosmid probes from the pseudoautosomal region
      PAR1, was performed. The results showed that the breakpoint maps approximately
      1,000 Kb from Ypter. The second idic(Y) chromosome was found in a boy with mild
      mental retardation, craniofacial anomalies, and the karyotype in lymphocytes
      47,X,+idic(Y)(q11.23),+i(Y)(p10)[77]/46,X,+i(Y)(p10)[23]. To our knowledge, such
      an association has not been previously described. FISH and PCR analysis indicated
      the presence of at least two copies of the SRY gene in all analyzed cells. Using
      17 PCR primers, the Yq breakpoint was shown to map between sY123 (DYS214) and
      sY121 (DYS212) loci in interval 5O in AZFb region. Possible mechanisms of
      formation of abnormal Y chromosomes and karyotype-phenotype correlations are
      discussed.

PMID- 11343333
TI  - VATER non-random association of congenital malformations: study based on data
      from four malformation registers.
AB  - This study was undertaken to find a strict, unbiased epidemiological delineation
      of the VATER non-random association of congenital malformations and, based on
      registry information, to identify a group of probable VATER association infants
      suitable for etiological analyses. Information on 5,260 infants with multiple
      malformations was collected from four large registers of congenital
      malformations. Data were analyzed using a statistical method in which various
      putative confounders were controlled for. Our results indicate the existence of a
      distinct group of malformations corresponding to the VATER association:
      esophageal atresia, anal atresia, upper preaxial limb reduction defects, and
      costo-vertebral malformations. A subdivision into an upper and a lower group of
      VATER association was indicated, with heart malformations associated with the
      upper group and kidney malformations associated with the lower group. Restricting
      the inclusion criteria for VATER association to the above mentioned core
      malformations, few infants seem to belong to the VATER association, thus limiting
      the possibilities of carrying out etiological analyses. A relatively large number
      of infants may belong to a family of related conditions among which VATER
      association is a subgroup. In the search for risk factors, a strict definition of
      the VATER association is needed in order to not dilute the study material with
      irrelevant cases. The present study provides such strict inclusion criteria.

PMID- 11343334
TI  - Approaches to the analysis of infants with multiple congenital anomalies.

PMID- 11343335
TI  - Mutation A1298C of methylenetetrahydrofolate reductase: risk for early coronary
      disease not associated with hyperhomocysteinemia.
AB  - Diminished activity of 5,10 methylenetetrahydrofolate reductase (MTHFR), a
      regulatory enzyme of homocysteine metabolism, may predispose to coronary artery
      disease (CAD). In a case-control study we determined the prevalence of two common
      MTHFR polymorphisms, C677T and A1298C, in 161 male patients under the age of 50
      years with angiographically documented CAD and compared it to that in 211 healthy
      controls. Genotyping was also performed in a random population sample, consisting
      of 149 men and 121 women at an average age of 40 years. The studied group had
      classic risk factors of atherosclerosis but did not differ in fasting plasma
      homocysteine, folic acid, and vitamin B12 levels in either the control group or
      population sample. The frequency of the 1298C allele was significantly higher in
      CAD (0.304) than in controls (0.199) or the population sample (0.235). Allele
      1298C showed a significant association with early-onset CAD both in homozygotes
      and in heterozygous carriers. These findings were further supported by
      comparisons with the population sample. Homozygosity for allele 677T showed a
      tendency to associate with CAD. Allele 1298C of MTHFR is associated with early
      onset CAD (carriers- RR = 1.71, 95% CI: 1.13-2.59; homozygotes- RR = 3.09, 95%
      CI: 1.36-7.02), even when blood homocysteine levels are not elevated.

PMID- 11343336
TI  - Absence of correlation between infantile hypotonia and foramen magnum size in
      achondroplasia.
AB  - Virtually all infants with achondroplasia exhibit variably severe hypotonia in
      infancy. This hypotonia contributes to delays in motor development and risks for
      sudden death. Some have proposed that this hypotonia is a direct result of
      impaired function of long tracts of the spinal cord, secondary to the intrinsic
      narrowing of the foramen magnum, which also is present in variable severity in
      all children with achondroplasia. We postulated that if foraminal constriction
      causes infantile hypotonia, then there should be a strongly positive correlation
      between foraminal size and severity of hypotonia. Therefore, clinical and
      computed tomographic data in 71 infants were retrospectively reviewed. We found
      no correlation. These results suggest that there is no direct relationship and
      foraminal size does not affect severity of hypotonia. Other potential
      explanations for this infantile hypotonia are considered.

PMID- 11343337
TI  - Neurological presentation of a congenital disorder of glycosylation CDG-Ia:
      implications for diagnosis and genetic counseling.
AB  - The congenital disorders of glycosylation (CDG) constitute a new group of
      recessively inherited metabolic disorders that are characterized biochemically by
      defective glycosylation of proteins. Several types have been identified. CDG-Ia,
      the most frequent type, is a multisystemic disorder affecting the nervous system
      and numerous organs including liver, kidney, heart, adipose tissue, bone, and
      genitalia. A phosphomannomutase (PMM) deficiency has been identified in CDG-Ia
      patients and numerous mutations in the PMM2 gene have been identified in patients
      with a PMM deficiency. We report on a French family with 3 affected sibs, with an
      unusual presentation of CDG-Ia, remarkable for 1) the neurological presentation
      of the disease, and 2) the dissociation between intermediate PMM activity in
      fibroblasts and a decreased PMM activity in leukocytes. This report shows that
      the diagnosis of CDG-Ia must be considered in patients with non-regressive early
      onset encephalopathy with cerebellar atrophy, and that intermediate values of PMM
      activity in fibroblasts do not exclude the diagnosis of CDG-Ia.

PMID- 11343338
TI  - Unique case of trisomy 2p24.3-pter with no associated monosomy.
AB  - We report a 3-year-old girl with trisomy 2p24.3-pter who presented with marked
      psychomotor delay and dysmorphic features. This patient represents the only known
      case of trisomy 2p24.3-2pter that does not involve an associated functional
      monosomy. In contrast to recent reports highlighting the fatal or serious
      complications in patients described as having partial trisomy 2p, this patient
      does not have significant birth defects or life threatening medical problems.
      Notably, this patient does not have a neural tube defect (NTD), which has been
      attributed to a putative locus at 2p24 in other patients with a partial trisomy
      2p.

PMID- 11343340
TI  - Angelman syndrome: mimicking conditions and phenotypes.
AB  - The diagnosis of Angelman syndrome (AS) can be confirmed by genetic laboratory in
      about 80% of cases. In 20%, the diagnosis remains clinical, but often there is
      uncertainty about the correctness of the clinical diagnosis and alternative
      diagnoses may be investigated. In evaluating individuals for AS in our center
      since 1989, we have encountered several mimicking conditions, and additional ones
      have been reported in the literature. Mimicking conditions can be grouped into
      the areas of chromosome, single gene, and symptom complex anomalies.
      Microdeletions or microduplications include chromosome regions 2,4,17, 22, and
      15. Single gene conditions include methylene tetrahydrofolate reductase
      deficiency (MTHFR), Rett syndrome, alpha-thalassemia retardation syndrome (ATR
      X), and Gurrieri syndrome. Symptom complexes include cerebral palsy, static
      encephalopathy, Lennox-Gastaut syndrome, autism spectrum disorder, pervasive
      developmental delay (PDD), and mitochondrial disorders. We present a review of
      these mimicking disorders to increase the awareness about conditions that can
      lead to an incorrect clinical diagnosis of AS.

PMID- 11343339
TI  - Aberrant splicing at catalytic site as cause of infantile onset glycogen storage
      disease type II (GSDII): molecular identification of a novel IVS9 (+2GT-->GC) in
      combination with rare IVS10 (+1GT-->CT).
AB  - Glycogen storage disease type II (GSDII) results from deleterious mutations in
      acid alpha-glucosidase gene. To date several mutant alleles have been studied
      including missense and nonsense mutations, insertions, small and large deletions
      as well as splice site mutations. Apart from IVS1 (- 13-->G), 525delT, and
      Delta18, the other mutations are rare and often unique to single patients.
      Moreover, the molecular findings also observed in the different ethnic groups
      makes it difficult to attempt to correlate genotype and phenotype to explain the
      origin of clinical variability. Even though there are no conclusive genotype
      phenotype correlations, the in frame splice site mutations identified up until
      now have been found associated with the juvenile/adult onset of GSDII. In this
      study we describe a novel in frame splicing defect, IVS9 (+2GT-->GC), identified
      in combination with the rare IVS10 (+1GT-->CT) mutation in a patient with classic
      infantile GSDII disease. Because both mutations occur at the catalytic site
      region, it is likely that the alteration of both catalytic function and steric
      conformation of the enzyme may be responsible for the most severe form of the
      disease.

PMID- 11343341
TI  - Grandmaternal origin of an isochromosome 18p present in two maternal half
      sisters.
AB  - The syndrome of tetrasomy 18p has been well documented in the literature. This is
      typically a result of a supernumerary isochromosome 18p, that has arisen during
      maternal meiosis II. This report presents clinical and molecular findings in two
      maternal half sisters with an isochromosome 18p. The isochromosome is inferred to
      have arisen during meiosis in the maternal grandmother and to have undergone
      mitotic and meiotic recombination in the mother of JJ and AT. The abnormal cell
      line may be restricted to the gonad in the mother as only normal 46,XX cells were
      detected by cytogenetic analysis of her blood or fibroblasts and physical
      examination revealed only normal findings. Thus, the isochromosome, although
      present at fertilization, must have been lost from the majority of embryonic
      precursor cells. This case raises important genetic counseling issues concerning
      recurrence risks.

PMID- 11343342
TI  - New syndrome characterized by sparse hair, prominent nose, small mouth,
      micrognathia, cleft palate, crumpled upper helices, digit anomaly, and mild
      developmental delay.
AB  - A brother and a sister show very similar clinical features, including sparse hair
      in the first year of life, prominent nose, small mouth, micrognathia, high arched
      palate or cleft palate, crumpled upper helices, flexion limitation of the distal
      interphalangeal joint of the fingers, and mild developmental delay. Their
      clinical appearance suggests a premature aging phenotype, but is not really
      compatible with the hitherto known syndromes of that group. The mode of
      inheritance is likely autosomal recessive.

PMID- 11343343
TI  - Metaphyseal dysplasia: a new autosomal dominant type in a large German kindred.
AB  - We describe a new autosomal dominant type of metaphyseal dysplasia (MD) in five
      generations of a German kindred. The main characteristics are metaphyseal
      widening and undermodeling of the tubular bones with Erlenmeyer flask-like
      appearance of the distal femora (typical of MD), with unusually severe varus
      deformity of the radii and flat exostoses of the long bones localized in the
      metaphyses. The skull is unaffected. Allelism with craniometaphyseal dysplasia
      (CMD) was excluded by linkage analysis.

PMID- 11343344
TI  - Not a new variant of the autosomal recessive multiple pterygium syndrome but the
      Bartsocas-Papas syndrome.

PMID- 11343346
TI  - It is necessary to perform high-resolution band chromosomes in any child with
      malformations, before making a diagnosis or establishing a possible relationship
      with any risk factor.

PMID- 11343348
TI  - Goldenhar anomaly in one triplet derived from intracytoplasmic sperm injection
      (ICSI).

PMID- 11343353
TI  - Data field standards and the Health Insurance Portability and Accountability Act.
AB  - The Administrative Simplification Title of the Health Insurance Portability and
      Accountability Act of 1996 addresses the creation and adoption of nationwide
      standards for the electronic exchange and confidentiality protection of all
      individually identified data used in health care administration. The U.S.
      Department of Health and Human Services (DHHS) is implementing standards under
      this law. In addition to new standards, the law mandates that the Congress pass a
      health information privacy bill by August 1999 or that the DHHS adopt privacy
      protections for health information by February 2000. Published in 2001 by John
      Wiley & Sons, Ltd.

PMID- 11343354
TI  - Designing linked micromap plots for states with many counties.
AB  - This paper describes the design of linked micromap plots for showing county
      estimates on a state by state basis. The linked micromap template was
      specifically developed to represent spatially indexed statistical summaries. Each
      plot shows regional names, spatial patterns and statistical patterns while
      linking them all together. Thus the design is useful for communicating summaries
      from a host of health and environmental studies. The specific design challenge in
      this paper is to create one-page plots for the states with 60 to 120 counties.
      While the county names and micromaps take up substantial space, the three
      examples demonstrate that there is sufficient space to represent two variables.
      The basic design has the potential for showing more. Consequently the new designs
      are suitable for presenting sophisticated summaries.

PMID- 11343355
TI  - A perspective from the press: how to help reporters tell the truth (sometimes).

PMID- 11343356
TI  - Statistical perspectives on confidentiality and data access in public health.
AB  - Confidentiality and disclosure limitation are topics that are inherently
      statistical but, until recently, they have received limited attention from
      statistical methodologists. That situation has changed considerably in the
      present decade. In this paper, we provide an introduction and overview of some
      statistical disclosure limitation issues that are of special relevance to public
      health studies and surveys, and the linkages to current research on bounds for
      multi-dimensional contingency table entries and 'simulated' categorical data. We
      also describe how these research methods relate to a new data access query system
      being developed for use by NCHS and other statistical agencies.

PMID- 11343357
TI  - Perspective: media coverage of emerging and re-emerging diseases behind the
      headlines.

PMID- 11343358
TI  - Contrasting Bayesian analysis of survey data and clinical trials.
AB  - Although both surveys and clinical trials are amenable to Bayesian hierarchical
      modelling, the general aims, constraints and actual analysis of each can often
      vary considerably. First, examples are presented showing how Bayesian
      hierarchical modelling can be used to produce estimates for small areas from
      survey data and, also, how it can be used to combine data from clinical trials.
      Then, it will be shown how surveys and clinical trials may differ with respect to
      the presence of design effects/selection biases and with the ability to validate
      models. The impact of the design on modelling will be highlighted and a class of
      sample selection models will be shown to help alleviate the design's influence.
      Although surveys generally have enough data to validate many features of a model,
      clinical trials may not, leaving sensitivity analysis as a means to prior
      acceptance. Some design issues, contrasting Bayesian with frequentist methods,
      will also be discussed. Published in 2001 by John Wiley & Sons, Ltd.

PMID- 11343359
TI  - Statistical models appropriate for designs often used in group-randomized trials.
AB  - Group-randomized trials are characterised by the allocation of identifiable
      groups rather than individuals to study conditions; members within those groups
      are then observed to assess the effect of the intervention. It is convenient to
      categorize the designs employed in group-randomized trials along two dimensions,
      each with two levels. The first distinguishes between designs having just one or
      two time intervals and those having three or more intervals. The second
      distinguishes between nested cohort and nested cross-sectional designs. Following
      a brief review of the design and analytic issues common to group-randomized
      trials, and their general solutions, this paper presents the adaptations of the
      mixed-model analysis of covariance and random coefficients models that are
      required for the four combinations that result from this categorization scheme.
      The assumptions, strengths and weaknesses of each model are discussed.

PMID- 11343360
TI  - Linking toxicology and epidemiology: the role of mechanistic modelling.

PMID- 11343361
TI  - Estimating the causal effects of smoking.
AB  - An important application of statistics in recent years has been to address the
      causal effects of smoking. There is little doubt that there are health risks
      associated with smoking. However, more general issues concern the causal effects
      due to the alleged misconduct of the tobacco industry or due to programmes
      designed to curtail tobacco use. To address any such causal question, assumptions
      must be made. Although some of the issues are well known in the statistical and
      epidemiological literature, there does not appear to be a unified treatment that
      provides prescriptive guidance on the estimation of these causal effects with
      explication of the needed assumptions. A 'conduct attributable fraction' is
      derived, which allows for arbitrary changes in smoking and non-smoking health
      care expenditure related factors in a counterfactual world without the alleged
      misconduct, and therefore generalizes the traditional 'smoking attributable
      fraction'. The formulation presented here, although described for the problem of
      estimating excess health care expenditures due to the alleged misconduct of the
      tobacco industry, is more general. It can be applied to any outcome, such as
      mortality, morbidity, or income from excise taxes, as well as to any situation in
      which consequences due to alleged misconduct (for example, of two entities, such
      as the tobacco and the asbestos industries) or due to hypothetical programmes
      (for example, extra smoking reduction initiatives) are to be estimated.

PMID- 11343362
TI  - Ethical challenges at the beginning of the millennium.
AB  - In the mid-1980s, the Centers for Disease Control and Prevention (CDC) recognized
      the need to study genetic risk factors for common diseases such as diabetes and
      heart disease. To take advantage of a rare opportunity to obtain a nationally
      representative, population-based sample to study genetic risk factors, the CDC
      collected and stored DNA as part of the Third National Health and Nutrition
      Examination Survey (NHANES III). At the time, the methods for studying these risk
      factors in large epidemiologic studies were not available. However, in the midst
      of planning for NHANES III, a revolution was occurring in the field of genetics.
      The resulting changes would provide a means to realize the goal of explaining why
      some people are more susceptible than others to risks such as elevated
      cholesterol or exposure to carcinogens. During this period, ethicists were
      increasingly asking questions about the safety and risks for participants in
      genetic research. Was genetic research different from other research? Were new
      rules for obtaining informed consent for genetic research needed, or should our
      methods of obtaining informed consent be equally rigorous for all research? When
      collection of the NHANES III DNA bank was complete in 1994, the CDC and the
      National Institutes of Health (NIH) held a workshop to address these questions.
      The published recommendations of this workshop stimulated a national debate that
      resulted in a significant change in the way genetic epidemiologic research is
      done in the United States including not only stored biologic specimens but data
      collected for one purpose but used for another. In 1999, the National Bioethics
      Advisory Commission (NBAC) published recommendations for the ethical use of human
      biological materials. The recommendations of the NBAC and policies and practices
      of the CDC about informed consent for research on stored tissue samples will
      serve as models for future epidemiologic research. The problems that were
      recognized in the national debate that ensued and the solutions that followed
      will affect the way we gain access to biological specimens and data in the 21st
      century. Published in 2001 by John Wiley & Sons, Ltd.

PMID- 11343363
TI  - Probabilistic population estimation of the size and overlap of data sets based on
      date of birth.
AB  - Probabilistic population estimation is a statistical procedure for deriving
      unduplicated counts of the number of people represented in data sets that do not
      include unique person identifiers and the number of people shared by data sets
      that do not share personal identifiers. Because the procedure relies on anonymous
      data sets, the personal privacy of individuals and the confidentiality of medical
      records is protected. This paper describes the mathematics of probabilistic
      population estimation, and applies the procedure to an important contemporary
      public policy issue.

PMID- 11343364
TI  - Logistic regression when binary predictor variables are highly correlated.
AB  - Standard logistic regression can produce estimates having large mean square error
      when predictor variables are multicollinear. Ridge regression and principal
      components regression can reduce the impact of multicollinearity in ordinary
      least squares regression. Generalizations of these, applicable in the logistic
      regression framework, are alternatives to standard logistic regression. It is
      shown that estimates obtained via ridge and principal components logistic
      regression can have smaller mean square error than estimates obtained through
      standard logistic regression. Recommendations for choosing among standard, ridge
      and principal components logistic regression are developed. Published in 2001 by
      John Wiley & Sons, Ltd.

PMID- 11343365
TI  - Maximally selected measures of evidence of disease clusters.
AB  - It is now common to read reports such as 'city A has a childhood cancer rate 30
      per cent higher than the national average'. Because the details about how the
      data was examined can greatly impact the conclusions, the epidemiologist then
      wants to know more information, such as 'over what time period' and 'how many
      other cancer types were examined'. For example, city A might have calculated
      cancer rates for many age groups within different regions of the city over many
      time intervals, but reported only the highest cancer rate discovered in a
      particular group. We will refer to such selective reporting as 'maximally
      selecting measures of evidence of disease clustering', or less formally as
      'fishing for statistical significance'. The objective of this paper is to study
      the behaviour of maximally selected statistics for measuring the extent of
      clustering in disease outbreaks. The original data is the time and location of
      each reported case of the disease. In some cases we are only given aggregates of
      the original data, such as the number of cases during a time period over a given
      region. We introduce new and review existing methods for correcting for the
      effect of making maximal selections in disease cluster detection. We consider
      three main cases with examples. We demonstrate via simulation and analytical
      approximations that some types of 'fishing' are simple to correct for while
      others are not.

PMID- 11343366
TI  - What can go wrong when you assume that correlated data are independent: an
      illustration from the evaluation of a childhood health intervention in Brazil.
AB  - The key analytical challenge presented by longitudinal data is that observations
      from one individual tend to be correlated. Although longitudinal data commonly
      occur in medicine and public health, the issue of correlation is sometimes
      ignored or avoided in the analysis. If longitudinal data are modelled using
      regression techniques that ignore correlation, biased estimates of regression
      parameter variances can occur. This bias can lead to invalid inferences regarding
      measures of effect such as odds ratios (OR) or risk ratios (RR). Using the
      example of a childhood health intervention in Brazil, we illustrate how ignoring
      correlation leads to incorrect conclusions about the effectiveness of the
      intervention.

PMID- 11343367
TI  - The effect of outliers on confidence interval procedures for cost-effectiveness
      ratios.
AB  - Cost-effectiveness ratio (CER) is defined as the ratio of the difference in cost
      between a test and standard health care programme to the difference in benefit,
      respectively. Methods to obtain confidence intervals for CERs are either variants
      of Fieller's method (1954), or bootstrap methods. We study the effect of outliers
      in cost measures on the precision of confidence interval procedures for CERs. In
      particular the performance of the procedures under single and multiple case
      influential deletion diagnostics, respectively, are evaluated. Simulation studies
      suggest that the bias-corrected percentile bootstrap procedure gives better
      precision and coverage under either diagnostic.

PMID- 11343368
TI  - Assigning time-linked exposure status to controls in unmatched case-control
      studies: alcohol use and nearly lethal suicide attempts.
AB  - In case-control studies, determination of alcohol consumption by cases
      immediately prior to the injury event is often conceptually straightforward.
      However, determination of consumption status by controls is difficult because
      they lack a reference point, especially when cases and controls are not
      individually matched. We describe a method of assigning alcohol consumption
      status to controls using a 24-hour drinking history, the distribution in time of
      case events, and the random assignment of a specific time period to each control
      subject. This methodology offers a practical approach for determining alcohol
      consumption status among control subjects immediately prior to a case event, when
      controls lack a reference point and have not been individually matched to cases.
      Published in 2001 by John Wiley & Sons, Ltd.

PMID- 11343369
TI  - A dynamic adaptation of the propensity score adjustment for effectiveness
      analyses of ordinal doses of treatment.
AB  - The propensity score adjustment is a method to reduce bias in observational
      studies. We propose a strategy that involves a novel combination of three data
      analytic techniques, which adapts the propensity adjustment for additional
      perturbations of longitudinal, observational studies. First, ordinal logistic
      regression examines propensity for ordinal doses of treatment. Second, a mixed
      model approach incorporates the multiple treatment trials and multiple episodes
      that are characteristic of chronically ill subjects. Finally, a mixed-effects
      grouped-time survival model incorporates the propensity score in treatment
      effectiveness analyses. The strategy that is applied here to an observational
      study of affective illness can also be used to evaluate the effectiveness of
      treatments for other chronic illnesses.

PMID- 11343370
TI  - Use of a density equalizing map projection in analysing childhood cancer in four
      California counties.
AB  - In this study, 401 cases of childhood cancer in four California counties in 1980
      1988 were analysed with the innovative methodology of density equalizing map
      projections. The data were originally collected and analysed by the California
      State Department of Health Services (DHS). In addition to the new analytic
      technique, the present analysis used population data more detailed and more
      accurate than those in the DHS analysis. The geographic boundaries of the 259
      census tracts in the study area were adjusted according to population at risk so
      as to make population density everywhere constant; then the 401 case locations
      were plotted on the density equalized map. If risk is everywhere equal, the
      resulting distribution of cases should be uniform except for statistical
      variation. The metric used was a measure of the variability of the density of
      cases on the density equalized map. The same metric was calculated for
      independent samples of artificial cases, generated under the null hypothesis of
      equal risk. The slight geographic non-uniformity observed among the real cases is
      well within the limits of variation observed in the samples of artificial cases.
      In agreement with results published by DHS, we conclude that there is no evidence
      for geographic variation of risk among the cases studied. Subsets of the data,
      selected by age, sex, race, time period and cancer site, yielded similar negative
      results.

PMID- 11343371
TI  - Modelling survival data with a cured fraction using frailty models.
AB  - Cure models have historically been utilized to analyse time-to-event data with a
      cured fraction. We consider the use of frailty models as an alternative approach
      to modelling such data. An attractive feature of the models is the allowance for
      heterogeneity in risk among those individuals experiencing the event of interest
      in addition to the incorporation of a cured component. Utilizing maximum
      likelihood techniques, we fit models to data concerning the recurrence of
      leukaemia among patients receiving autologous transplantation treatment. The
      analysis suggests that the gamma frailty mixture model and the compound Poisson
      improve on the fit of the leukaemia data as compared to the standard cure model.

PMID- 11343372
TI  - A GEE approach to estimating sensitivity and specificity and coverage properties
      of the confidence intervals.
AB  - A generalized estimating equation (GEE) approach is used to estimate the
      sensitivity and specificity of five non-culture screening tests for detecting
      Chlamydia trachomatis in endocervical specimens from women attending family
      planning clinics. Since the estimates of these parameters can be very close to
      the upper limit of one, confidence interval construction based on the traditional
      approaches, such as the delta method or a back-transformation approach, may not
      have the stated coverage. We compare different approaches to calculating
      confidence intervals for the sensitivity and specificity from the results of the
      GEE approach. These methods include the delta method, a back-transformation
      approach, and a bootstrap approach. In addition, we use simulations to
      investigate the estimated coverage rates of the delta method and the back
      transformation approach. Published in 2001 by John Wiley & Sons, Ltd.

PMID- 11343373
TI  - Multiple imputation in public health research.
AB  - Missing data in public health research is a major problem. Mean or median
      imputation is frequently used because it is easy to implement. Although multiple
      imputation has good statistical properties, it is not yet used extensively. For
      two real studies and a real study-based simulation, we compared the results after
      using multiple imputation against several simpler imputation methods. All
      imputation methods showed similar results for both real studies, but somewhat
      different results were obtained when only complete cases were used. The
      simulation showed large differences among various multiple imputation methods
      with a different number of variables for creating the matching metric for
      multiple imputation. Multiple imputation using only a few covariates in the
      matching model produced more biased coefficient estimates than using all
      available covariates in the matching model. The simulation also showed better
      standard deviation estimates for multiple imputation than for single mean
      imputation.

PMID- 11343378
TI  - Acute lymphoblastic leukemia in the elderly: The Edouard Herriot Hospital
      experience.
AB  - Data on all patients with acute lymphoblastic leukemia (ALL) aged 60 or older,
      referred to our institution over a 18-year period, were studied to determine the
      incidence and range of clinical and biological subtypes, and the outcome of
      different therapeutic approaches. Sixty-nine ALL cases (median age: 68 years)
      were diagnosed between 1980 and 1998 (18% of all adult ALL seen during this
      period). Ten of them (14%) had a past history of previous malignancy. Karyotypic
      analysis was performed successfully in 42 cases. Ten patients were diagnosed as
      Philadelphia chromosome positive (Ph(+)) ALL. Immunophenotyping was performed in
      63 cases. Fifty-six patients had B-cell lineage ALL. T lymphoid markers were
      observed only in 5 cases. Co-expression of myeloid markers was observed in 19% of
      tested cases. Five patients died before any chemotherapy could be given. All
      other patients received "curative" treatment according to different protocols
      used during the period of study. Overall complete remission (CR) rate of these
      patients was 62% (95% confidence interval (CI): 50-74%). Thirty-nine patients
      achieved CR after one course of chemotherapy and 4 patients after salvage
      therapy. Median disease-free survival (DFS) of the entire cohort was 8.3 months
      (95% CI: 5-12.8 months) and median overall survival was 7 months (95% CI: 6-10
      months). In multivariate analysis, the presence of hemorrhage (P = 0.02) was a
      poor prognostic for CR achievement. Higher WHO performance status (P = 0.003) and
      the presence of hemorrhage (P = 0.01) at diagnosis were poor prognostics for
      overall survival. When patients were stratified into three groups according to
      the time of admission, survival appeared significantly longer for patients
      admitted between July 1992 and December 1998 (median overall survival at 10
      months) than for patients admitted before July 1992 (P = 0.04). "Age-adapted"
      therapy appeared superior to "young adult-like" therapy in terms of CR rate (96%
      versus 60%; P = 0.007). However, "age-adapted" therapy did not show any advantage
      in terms of DFS or overall survival, making the difference in CR rates
      questionable. We conclude that the pejorative overall outcome in elderly ALL
      points to the need for new therapeutic trials taking into account the specific
      characteristics of ALL in this age group.

PMID- 11343377
TI  - Changes in the expression of surface receptors on lymphocyte subsets in the
      elderly: quantitative flow cytometric analysis.
AB  - The immunophenotype of circulating lymphocytes, including the intensity
      expression of surface receptors, changes with ageing. Until now, no results of
      systematic studies on age-dependent changes with respect to the expression of the
      major lymphocyte surface receptors in healthy elderly subjects have been
      reported. In order to identify age-related changes in both representation and
      immunophenotype of lymphocyte populations, we investigated, by means of triple
      color whole-blood immunostaining and quantitative flow cytometry, the percent
      values and the absolute numbers, as well as the levels of surface antigen
      expression or antigen molecules per cell (ABC values x 10(3)), of different
      peripheral blood lymphocyte subsets from 23 healthy elderly subjects and 13 young
      donors. Naive (CD45RA+CD3+) T cells, total B cells, and CD5+ B lymphocytes are
      decreased (22%, 6%, 0.8% vs. 30%, 12%, 1.4%, respectively), whereas activated
      (HLA-DR+CD3+) and memory (CD45RO+CD3+) T cells, CD3+CD7- T lymphocytes, and
      lymphocytes expressing the NK marker CD56 are expanded in the elderly (2%, 53%,
      13%, 6% vs. 0.8%, 45%, 8%, 8%, respectively). Moreover, T lymphocytes from
      elderly individuals express lower CD3 (61 +/- 10) compared to young (69 +/- 10).
      Considering the different T-cell populations, CD3 antigen is respectively
      decreased on CD45RO+ T cells (55 +/- 14 vs. 66 +/- 14) and up-regulated on CD56+
      T lymphocytes (62 +/- 21 vs. 45 +/- 20). Increased CD8 expression characterizes
      CD3+CD7- lymphocytes (70 +/- 34 vs. 44 +/- 17) while HLA-DR on activated T cells
      is lower in old (39 +/- 7) than young (46 +/- 9) donors. CD7 is down-regulated
      both in T (22 +/- 3 vs. 28 +/- 3) and NK (48 +/- 18 vs. 71 +/- 18) cells, whereas
      CD2 expression, unchanged on NK cells, is up-regulated on T lymphocytes (54 +/-
      10 vs. 41 +/- 8). Age-related changes in B-cell antigen expressions were also
      found: CD20 is increased (124 +/- 23 vs. 105 +/- 16) whereas, despite the
      unchanged CD5 expression of T cells, CD5 intensity on the B-cell subset co
      expressing this antigen is higher in old (49 +/- 37) than in young (22 +/- 4)
      people. The observed changes in the expression of functionally important cellular
      receptors can contribute to the remodeling of immune function characteristic of
      the elderly. Moreover, since quantitative flow cytometry is becoming widely
      employed in clinical practice, our results also contribute to the assessment of
      specific age-dependent antigen expression changes to be considered for diagnostic
      approaches in the elderly.

PMID- 11343379
TI  - p53, Mdm2, and c-Myc overexpression is associated with a poor prognosis in
      aggressive non-Hodgkin's lymphomas.
AB  - The expression of p53, p21/WAF-1, Mdm2, c-Myc, and proliferating cell nuclear
      antigen (PCNA) proteins was examined by the immunohistochemistry of paraffin
      embedded tissues of 62 patients with aggressive non-Hodgkin's lymphomas (NHL) and
      correlated to clinical data. Expression of p53, p21/WAF-1, Mdm2, and c-Myc
      protein was observed in 17 out of 62 cases (30%), 25 out of 60 (42%), 13 out of
      44 (30%), and 39 out of 51 (76.5%), respectively. The p53+/p21WAF-1 phenotype,
      which is more frequently found in p53 mutations, was associated with a worse
      overall survival (P = 0.04) and with a lower rate of complete response (CR) (PF =
      0.01). p53 and c-Myc negative expression was related to a better response to
      chemotherapy (PF = 0.005 and 0.035, respectively). The expression of p53, c-Myc,
      and Mdm2 was related to a shortened overall survival (P < 0.001, 0.05, and 0.037,
      respectively), suggesting that the expression of these proteins could be
      associated with a poor outcome in these patients.

PMID- 11343380
TI  - Ultrasound-guided fine needle biopsy of the spleen: high clinical efficacy and
      low risk in a multicenter Italian study.
AB  - The aim of this study was to evaluate the clinical efficacy and safety of the
      ultrasound-guided fine needle biopsy (UG-FNB) of the spleen in a large population
      of patients. We collected retrospectively the findings concerning the application
      of UG-FNB of the spleen from eight Italian clinical centers that utilized this
      technique for at least ten years. A data schedule was sent to all centers to
      collect information about techniques, results, and complications of UG-FNB of the
      spleen. We analyzed 398 biopsy procedures both on focal lesions (257 cases) and
      on splenic parenchyma (141 cases). The overall accuracy was 90.9% for the series
      as a whole, 84.9% for cytological sampling, 88.3% for microhistological sampling,
      and 90.3% for both cytological and histological sampling (double biopsy). Tissue
      core biopsy yielded better overall accuracy in patients with suspected splenic
      involvement by lymphoma (90.9% vs. 68.5% for cytology). The complication rate was
      low (no death cases, less than 1% for major complications, and 5.2% for all
      complications). No predictive factors were able to detect high-risk situations.
      The operator's skill (higher number of performed procedures) was significantly
      related to better overall accuracy. Conversely, the complication rate was not
      affected. UG-FNB of the spleen is a very effective diagnostic procedure with low
      risk for the patient. Aspiration cytology and core needle biopsy showed similar
      diagnostic yields, except for the diagnosis of splenic lymphoma, in which core
      needle biopsy obtained better results.

PMID- 11343381
TI  - Bone marrow aspiration, biopsy, and culture in the evaluation of HIV-infected
      patients for invasive mycobacteria and histoplasma infections.
AB  - Bone marrow (BM) aspiration and biopsy are used commonly in clinical practice to
      diagnose invasive tissue infections caused by Mycobacterium avium intracellulare
      (MAC), Mycobacterium tuberculosis (TB), and Histoplasma capsulatum (HC) in
      patients with human immunodeficiency virus-1 (HIV) infection. However, the value
      of these invasive procedures relative to other diagnostic approaches has not been
      clearly defined. To determine the value of BM culture and BM histology in the
      diagnosis of opportunistic MAC/TB and HC infections in immunosuppressed patients
      with HIV, we retrospectively reviewed the records of 56 adult patients with HIV
      who underwent a single BM aspiration, biopsy, and culture because of unexplained
      fever and/or other clinical features suggestive of MAC/TB or HC infection. Thirty
      two patients (57%) were ultimately diagnosed with MAC/TB or HC infection by
      positive cultures of BM, blood, sputum, or bronchoalveolar lavage fluid or by the
      histologic detection of organisms in biopsies of BM or other tissues. The
      diagnostic sensitivity of BM cultures was equal to that of blood cultures (20/32,
      or 63%). Granuloma and/or histologically apparent organisms were seen in BM
      biopsy specimens in 11 of 32 individuals (34%) ultimately diagnosed with MAC/TB
      or HC infections. Among these 11 cases, both granuloma and acid-fast staining
      organisms were found in the BM biopsy specimens of 2 individuals for whom both BM
      and blood cultures were negative. Certain clinical symptoms and signs at the time
      of BM examination were found by logistic regression analysis to be significantly
      associated with a subsequent diagnosis of MAC/TB or HC infections; these included
      high fever, long duration of febrile days prior to BM examination, and elevated
      direct bilirubin. In conclusion, while the diagnostic sensitivity of BM cultures
      was found to be no greater than that of blood cultures in detecting MAC/TB or HC
      infections in immunosuppressed HIV+ patients, histopathologic examination of BM
      specimens resulted in the relatively rapid identification of nearly one third of
      infected patients who underwent BM examination, and also identified infections in
      some patients who were culture negative. These findings support the continued use
      of BM aspiration, biopsy, and culture for the diagnosis of opportunistic MAC/TB
      or HC infections in immunosuppressed HIV+ patients, particularly when selected
      clinical features are present.

PMID- 11343382
TI  - Two common genetic thrombotic risk factors: factor V Leiden and prothrombin
      G20210A in adult Turkish patients with thrombosis.
AB  - The prevalence of genetic risk factors for thrombosis varies greatly in different
      parts of the world, both in patients with thrombosis and in the general
      population. Factor V Leiden (FVL) and prothrombin G20210A (PT G20210A) mutations
      are the most common genetic defects leading to thrombosis. We have previously
      reported that those two thrombotic risk alleles are frequently found in Turkish
      children with thrombosis. The aim of the present study was to investigate the
      frequency of FVL and PT G20210A and their clinical manifestations in adult
      Turkish patients with thrombosis. Between January 1997 and February 2000, 146
      patients with documented thrombosis were investigated in our center for the
      presence of the FVL and PT G20210A mutations. Forty-five of 146 patients with
      thrombosis (30.8%) were detected to have FVL mutation. Among those cases with the
      FVL mutation, seven (4.8%) had homozygote and 38 (26%) had heterozygote mutation.
      The PT G20210A mutation was detected in 10 of the 146 patients with thrombosis
      (6.8%). Another six cases (4.1%) had both FVL and PT G20210A mutations. The
      overall frequency of these two common risk alleles in our adult population with
      thrombosis was 41.6%. Our findings reveal that FVL and PT G20210A mutations are
      significant genetic risk factors contributing to the pathophysiology of
      thrombosis in the Turkish population.

PMID- 11343384
TI  - High-dose cytosine arabinoside and idarubicin treatment of chronic myeloid
      leukemia in myeloid blast crisis.
AB  - Chronic myeloid leukemia in myeloid blast crisis (CML-MBC) is highly resistant to
      standard induction chemotherapy regimens. Anecdotal results from previous
      clinical trials support the concept of dose escalation in patients with CML-MBC.
      Eight patients with CML-MBC were treated with cytosine arabinoside (Ara-C) 1.5
      3.0 g/m2 intravenously over 1 hr every 12 hr for 12 doses and idarubicin 12 mg/m2
      intravenously daily for 3 days. Sixteen previous reports describing the use of
      Ara-C-based chemotherapy regimens in patients with CML-MBC were also reviewed.
      Our patients' median age was 62 years (range, 42-69 years). One patient achieved
      complete hematologic remission (95% confidence interval, 0.3%, 53%). The median
      survival for our patients was 7.3 months. These results were not different from
      previous published reports using Ara-C-based chemotherapy regimens to treat CML
      MBC. In summary, the combination of high-dose Ara-C and idarubicin did not
      improve the overall prognosis of patients with CML-MBC. Innovative approaches
      need to be explored for this patient population.

PMID- 11343383
TI  - DNA content of granulocytes, monocytes, and lymphocytes in the bone marrow smears
      of patients with myelodysplastic syndromes.
AB  - Recently, we have reported a high incidence of DNA hypodiploidy defined as DNA
      index (DI) in blasts/promyelocytes from 39 patients with myelodysplastic
      syndromes (MDS) found to be without a relationship to cytogenetics. In the
      present study the DNA content (DI) in granulocytes, monocytes, and lymphocytes
      measured in the same bone marrow smears from the above patients are reported. DNA
      hypodiploidy was found in mature cells, not only in myeloid cells (granulocytes
      and monocytes) but also in lymphocytes. A lower mean DI in each cell type of
      patients compared to controls was found. Pairwise comparison of the mean DI (+/
      SE) in 32 patients with normal (n = 22) and abnormal (n = 10) cytogenetics and
      controls (n = 8) showed a significantly (P < 0.01) lower value for each group of
      patients, respectively, in all cell types. No difference was found between the
      two groups of patients. Presence of weak-Feulgen stained nuclei (DI < 0.40) in
      granulocytes and monocytes was more pronounced in patients expressing DNA
      hypodiploid immature cell populations, but only occasionally in lymphocytes,
      suggesting a link to an apoptotic event and intramedullary cell death. DNA
      hypodiploidy is shown to be a common feature even in mature cell populations in
      MDS bone marrows. Clonality, by means of DNA content, appears reasonable as
      regards the granulocytes and monocytes. DNA hypodiploid lymphocytes, on the other
      hand, might be small blasts (stem cells) or dying cell populations of unknown
      origin.

PMID- 11343386
TI  - Reticulocyte subpopulations and reticulocyte maturity index (RMI) rise as body
      iron status falls.
AB  - To investigate the influence of body iron status on reticulocyte subpopulations
      and reticulocyte maturity index (RMI), we measured serum iron markers,
      fluorescent intensity of reticulocytes, and serum transferrin receptor (sTfR)
      concentrations in 374 females aged 14-19 years. Reticulocyte subpopulations were
      analyzed by flow cytometry, and sTfR concentration was measured by enzyme
      immunoassay. There were no significant differences in the values of reticulocyte
      subpopulations and RMI between ferritin alone-depleted group and healthy
      controls. However, middle- and high-fluorescence reticulocytes and RMI were
      significantly higher in both the serum iron- and serum ferritin-depleted groups
      than in the ferritin alone-depleted group. Middle-fluorescence reticulocytes and
      RMI increased gradually as the body iron store was depleted and were 3.4- and 3.6
      fold higher, respectively, than normal controls, when the subjects attained a
      frank iron-deficiency anemia. There were no significant changes in the values of
      red blood cells or total reticulocyte counts during iron-depleted states. The
      mean value of sTfR (3.98 mg/l) in the subjects with RMI > or = 1.5% was
      significantly higher than that (2.26 mg/l) in the subjects with RMI < 1.5% (P <
      0.01). The sTfR concentration correlated significantly with RMI (r = 0.61, P <
      0.01) and middle-fluorescence reticulocytes (r = 0.59, P < 0.01). In short, body
      iron depletion induces elevation of immature reticulocyte fractions and RMI.

PMID- 11343385
TI  - Population differences in von Willebrand factor levels affect the diagnosis of
      von Willebrand disease in African-American women.
AB  - Diagnosis of von Willebrand disease (vWD) is based on a panel of laboratory tests
      that measure the amount and function of von Willebrand factor (vWF). In
      population studies, vWF is higher in African Americans than Caucasians. Bleeding
      time, factor VIII activity (FVIII), vWF antigen (vWF:Ag), "vWF activity" ELISA
      (vWF:Act), ristocetin cofactor (vWF:RCof), and ristocetin-induced platelet
      aggregation (RIPA) were measured on 123 women with menorrhagia and 123 randomly
      selected control women; 70 cases and 76 controls were African American. Among
      controls, African Americans had significantly higher levels of vWF:Ag (mean 120
      vs. 102 U/dl, P = 0.017). Among all subjects, African Americans had higher levels
      of vWF:Ag (mean 123 vs. 103, P = 0.001), vWF:Act (mean 101 vs. 89, P = 0.006),
      and FVIII (mean 118 vs. 104, P = 0.008). VWF:RCof did not differ between races
      (93 vs. 94 U/dl). RIPA was reduced in African Americans (P < 0.0001). In both
      races, women with type O blood differed significantly from those with other ABO
      types in vWF:Ag, vWF:Act, FVIII, and vWF:RCof. Based on criteria of two or more
      tests below race- and ABO-specific reference ranges, 6.5% of menorrhagia cases
      and 0.8% of controls were classified as having vWD, or its phenocopy. Among
      Caucasians, no controls and 7 cases (15.6%) were classified as affected, and in
      African Americans, 1 control (1.3%) and 1 case (1.4%) were so classified. Racial
      differences in vWF further complicate the issues surrounding diagnosis of vWD.
      The finding of increased vWF:Ag not accompanied by increased vWF:RCof has
      implications for understanding the structure-function relationships of vWF.
      Published 2001 Wiley-Liss, Inc.

PMID- 11343387
TI  - Pulmonary leukostasis: role of perfusion lung scan in diagnosis and follow up.
AB  - A patient with hyperleukocytic myelomonocytic leukemia who presented to the
      emergency room with sudden pleuritic chest pain and dyspnea is reported. Clinical
      manifestations included dyspnea tachypnea and hyperventilation. Blood gas
      analysis revealed hypoxemia, hypocarbia, and respiratory alkalosis. Chest X ray
      was normal, and perfusion lung scan revealed a diffuse vascular occlusive pattern
      compatible with pulmonary leukostasis. The patient underwent immediate
      leukapheresis with subsequent mitigation of symptoms. A second perfusion lung
      scan showed evidence of significant improvement. To our knowledge this is the
      first published case of hyperleukocytosis presenting with pulmonary leukostasis
      that was successfully diagnosed and followed by serial perfusion lung scan.

PMID- 11343388
TI  - Immune thrombocytopenia: a rare presenting manifestation of tuberculosis.
AB  - We report the case of a 49 year-old male who presented with immune
      thrombocytopenia (ITP)-induced epistaxis and generalized purpura. During the same
      hospitalization the patient was also found to have clinical, microbiological,
      histological, and roentgenographic evidence of disseminated mycobacterial
      tuberculosis (TB). The hematological and infectious abnormalities, which did not
      respond to high-dose intravenous corticosteroids and immune globulin (IVIg),
      resolved after anti-tuberculous treatment. Herein we review the characteristics
      of this rarely documented association.

PMID- 11343389
TI  - Extreme warfarin sensitivity in siblings associated with multiple cytochrome P450
      polymorphisms.
AB  - Warfarin use is complicated by an erratic dose response. Warfarin is metabolized
      by two distinct subfamilies of the cytochrome P450 (CYP) complex. We describe two
      siblings with extreme sensitivity to warfarin who share an unusual CYP genotype.
      These individuals illustrate both the importance of genetics in influencing the
      metabolism of warfarin as well as the potential utility of genetic testing as a
      guide to prescribing this medication.

PMID- 11343390
TI  - Chlorambucil/prednisone-induced seizures in a patient with non-Hodgkin's
      lymphoma.

PMID- 11343391
TI  - Apoptotic cells in a peripheral blood smear in the context of EBV infection.

PMID- 11343392
TI  - Detection of a rare splice acceptor site mutation (IVS I nt 130 G-->C) of the
      beta globin gene in 3 patients of Eastern India.

PMID- 11343393
TI  - Depression and suicide: what is the true risk?

PMID- 11343394
TI  - Strokes and depression.

PMID- 11343395
TI  - Ondansetron for alcoholics.

PMID- 11343396
TI  - On call. My wife's doctor gave her Premarin for her cholesterol. I know it's a
      female hormone, but my cholesterol is also high, and I wonder if it could help
      me, too.

PMID- 11343397
TI  - By the way, doctor... Antibiotics and heart disease. I have a question about the
      use of antibiotics as a treatment for heart disease. It seems like people would
      use them on a continuous basis. Yet isn't widespread antibiotic use now being
      discouraged because it may breed antibiotic-resistant germs?

PMID- 11343398
TI  - By the way, doctor... Can a pacemaker prolong dying? I just got a pacemaker put
      in. It has helped me a lot. But I'm wondering if it will prolong the process of
      dying by continuing artificial stimulation of my heart.

PMID- 11343399
TI  - Ask the doctor. Recently, I read that the ACE inhibitor ramipril is very good at
      preventing heart problems, particularly in people with diabetes. I'm diabetic,
      and for years I have been on a different ACE inhibitor (lisinopril). Should I be
      taking ramipril instead?

PMID- 11343400
TI  - Cloning and postharvest expression of serine proteinase transcripts in the
      cultivated mushroom Agaricus bisporus.
AB  - Increases in both the levels and the activity of serine proteinase have been
      previously described in the senescing mushroom Agaricus bisporus. cDNA encoding
      serine proteinase was amplified by reverse transcriptase-polymerase chain
      reaction using a degenerate primer based on the N-terminal sequence of a
      previously isolated A. bisporus serine proteinase and then cloned. The cDNA was
      sequenced and shown to be homologous to those of other fungal serine proteinases.
      Northern analysis showed that this serine proteinase gene (Spr1) was not
      expressed in freshly harvested sporophores but was strongly up-regulated
      postharvest and found almost entirely in the stipe of the sporophore
      (approximately 0.08% of mRNAs 2 days after harvest). Low-level expression was
      detectable in the flesh (pileus trama) and gill (lamellae) tissues of the cap,
      but none was detected in the skin (pilei pellis). In three of the cloned cDNAs,
      sequence analysis showed that the poly(A) tail starts at different positions.
      Expression of Spr1 in Escherichia coli caused restricted colony growth.

PMID- 11343401
TI  - Structure and function analysis of the calcium-related gene spray in Neurospora
      crassa.
AB  - The spray gene was cloned, and wildtype and mutant alleles were sequenced.
      Spray(+) has a 3452-bp open reading frame plus seven introns. The spray mutant
      had a T --> G transversion close to the carboxyl end, creating a stop codon
      (TGA). The sequence shows no match to genes of known function, but the carboxyl
      end shows seven transmembrane domains and matches putative membrane proteins of
      yeast. The most abundant transcript detected was 4.4 kb in size. Repeat-induced
      point mutagenesis produced the mutant spray phenotype. Electrophysiological
      analysis showed that ion fluxes in the spray plasma membrane are normal;
      furthermore, whereas the spray mutant was known to have no organelle-based
      calcium fluorescence, the cytosol shows a tip-high calcium gradient. The spray
      mutant is sensitive to calcineurin inhibitors. The results suggest that the SPRAY
      protein is located in an organellar membrane, regulating the distribution of
      Ca(2+) via calcineurin.

PMID- 11343402
TI  - The hydrophobin HCf-1 of Cladosporium fulvum is required for efficient water
      mediated dispersal of conidia.
AB  - Six hydrophobin genes (HCf-1 to -6) have thus far been identified in the tomato
      pathogen Cladosporium fulvum. HCf-1 to -4 are Class I hydrophobins and HCf-5 and 
      6 are Class II hydrophobins. In this paper we describe the isolation of deletion
      mutants that lack HCf-1, HCf-2, or both these genes. Global down-regulation of
      the expression of Class I hydrophobins is achieved by homology-dependent gene
      silencing. Analysis of the mutant strains shows that HCf-1 confers hydrophilic
      character to the conidia and this facilitates the dissemination of conidia on the
      surface of water droplets. Other Class I hydrophobins, such as HCf-3 or HCf-4,
      may be involved in the development and germination of conidia.

PMID- 11343403
TI  - vvd is required for light adaptation of conidiation-specific genes of Neurospora
      crassa, but not circadian conidiation.
AB  - con-10 and con-6 are two of the conidiation (con) genes of Neurospora crassa that
      were identified based on their preferential expression during macroconidiophore
      development. They are also regulated by several other environmental stimuli
      independent of development, including a transient induction by light. We
      identified an allele of vivid (vvd) in a mutant screen designed to obtain strains
      with altered expression of con-10. vvd mutants display enhanced carotenoid
      pigmentation in response to light. In addition, con-10 and con-6 show a
      heightened response to photoinduction. We tested the function of the light
      responsive circadian clock in the vvd mutant and found no major defect in the
      circadian rhythm of conidiation or light regulation of a key clock component,
      frequency (frq). We conclude that vvd is primarily involved in a process of light
      dependent gene repression, called light adaptation. Although a number of gene
      products are known to control light induction in fungi, vvd is the first gene
      shown to have a role in adaptation to constant light.

PMID- 11343404
TI  - The cAMP signal transduction pathway mediates resistance to dicarboximide and
      aromatic hydrocarbon fungicides in Ustilago maydis.
AB  - The cAMP signal transduction pathway mediates the switch between yeast-like and
      filamentous growth and influences both sexual development and pathogenicity in
      the smut fungus Ustilago maydis. Signaling via cAMP may also play a role in
      fungicide resistance in U. maydis. In particular, the adr1 gene, which encodes
      the catalytic subunit of the U. maydis cAMP-dependent protein kinase (PKA), is
      implicated in resistance to the dicarboximide and aromatic hydrocarbon
      fungicides. In this study, we examined the sensitivity of PKA to vinclozolin and
      could not demonstrate direct inhibition of protein kinase activity. However, we
      did find that mutants with disruptions in the ubc1 gene, which encodes the
      regulatory subunit of PKA, were resistant to both vinclozolin and chloroneb. We
      also found that these fungicides altered the morphology of both wild-type and
      ubc1 mutant cells. In addition, strains that are defective in ubc1 display
      osmotic sensitivity, a property often associated with vinclozolin and chloroneb
      resistance in other fungi.

PMID- 11343405
TI  - Reality monitoring of performed and imagined interactive events: developmental
      and contextual effects.
AB  - Age differences in reality monitoring of interactive events were examined among 4
      year-olds, 8-year-olds, 12-year-olds, and adults. Participants engaged in some
      interactions and imagined others. Afterward, they were asked to determine whether
      each action was performed, imagined, or new. This memory test was repeated 1 week
      later. The 4-year-olds had more difficulty discriminating imagined actions than
      the two oldest age groups. Imagined actions were more often confused with
      performed ones than the reverse, though this bias was significant only for the
      two younger age groups. Reality monitoring decreased over time, especially for
      imagined items. Activities in which the participant was the agent of action were
      discriminated better than those in which someone else was the agent of action.
      Object use during the activity increased the discrimination of imagined actions,
      especially after the delay. Similarity among actions had no effect. Implications
      for child eyewitness testimony are discussed.

PMID- 11343406
TI  - Modeling face identification processing in children and adults.
AB  - Two face identification experiments were carried out to study whether and how
      children (5-year-olds) and adults integrate single facial features to identify
      faces. Using the paradigm of the Fuzzy Logical Model of Perception each
      experiment used the same expanded factorial design, with three levels of eyes
      variations crossed with three levels of mouth variations as well as their
      corresponding half-face conditions. In Experiment 1, an integration of facial
      features was observed in adults only. But, in adjusting the salience of the
      features varied, the results of Experiment 2 indicate that children and adults
      evaluated and integrated information from both features to identify a face. A
      weighted Fuzzy Logical Model of Perception fit the judgments significantly better
      than a Single Channel Model and questions previous claims of holistic face
      processing. Although no developmental differences in the stage of the integration
      of facial information were observable, differences between children and adults
      appeared in the information used for face identification.

PMID- 11343407
TI  - Understanding children's activity memory: the role of outcomes.
AB  - In three experiments the effectiveness of activity outcomes as memory cues was
      investigated. In the first experiment, 5-year-olds participated in four
      activities. In two of these activities, action results were maintained during the
      unfolding of the activity and perceptually preserved in the activity's end
      product. In the other two activities, action results "disappeared" from view
      during the activity and were transformed within the end product. Each activity
      was recalled under one of four cue conditions: verbal, object, action, and
      reenactment. For half of the children, the end product was also present during
      retrieval. Memory for the two types of activities varied with cue condition and
      with the presence of the end product. In a second experiment, children attempted
      to describe how the end products could be recreated from the materials used in
      the activities without participating in them. Patterns of performance confirmed
      that memory and not inference was responsible for the effects observed in the
      first experiment. In a third experiment, 5- and 7-year-olds participated in
      activities of the two types. Within each, picture supports were provided to
      investigate whether the perceptual availability of action results during encoding
      influences memory. Results are discussed with respect to an activity memory
      framework and implications for science education.

PMID- 11343408
TI  - The relations between phonological processing abilities and emerging individual
      differences in mathematical computation skills: a longitudinal study from second
      to fifth grades.
AB  - The primary purpose of this longitudinal correlational study was to examine
      relations between phonological processing abilities and emerging individual
      differences in math computation skills and also to investigate the source of
      covariation between reading and math computation skills in a random sample (n =
      201). Phonological memory, rate of access to phonological codes in long-term
      memory, and phonological awareness were uniquely associated with growth in
      estimated total number of computation procedures mastered (general computation
      skills) from 92.5 to 134.8 months in age, although the contributions of the first
      two abilities were developmentally limited. Phonological processing almost
      completely accounted for the associations between reading and general computation
      skills. Evidence of bidirectional relations between general computation skills
      and simple arithmetic problem solving speed was found.

PMID- 11343409
TI  - I(Kr): the hERG channel.
AB  - G.-N. Tseng. I(Kr): The hERG Channel. Journal of Molecular and Cellular
      Cardiology (2001) 33, 835-849. The rapid delayed rectifier (I(Kr)) channel is
      important for cardiac action potential repolarization. Suppressing I(Kr)function,
      due to either genetic defects in its pore-forming subunit (hERG) or adverse drug
      effects, can lead to long-QT (LQT) syndrome that carries increased risk of life
      threatening arrhythmias. The implication of I(Kr)in cardiac arrhythmias and in
      anti-arrhythmic/pro-arrhythmic actions of drugs has driven intensive research
      interests in its structure-function relationship, the linkage between LQT
      associated mutations and changes in channel function, and the mechanism of drug
      actions. This review will cover the following topics: (1) heterogeneous
      contribution of I(Kr)to action potential repolarization in the heart, (2)
      structure-function relationship of I(Kr)/hERG channels, (3) role of regulatory &
      bgr; subunits in I(Kr)/hERG channel function, (4) structural basis for the unique
      pharmacological properties of I(Kr)/hERG channels, and (5) I(Kr)/hERG channel
      modulation by changes in cellular milieu under physiological and pathological
      conditions of the heart. It is anticipated that further advances in our
      understanding of I(Kr)/hERG, particularly in the areas of roles of different (&
      agr; and & bgr;) subunits in native I(Kr)function, alterations in I(Kr)function
      in diseased hearts, and the 3-dimensional structure of the I(Kr)/hERG pore based
      on homology modeling using the KcsA model, will help us better define the role of
      I(Kr)in arrhythmias and design therapeutic agents that can increase I(Kr)and are
      useful for LQT syndrome.

PMID- 11343410
TI  - The molecular physiology of the cardiac transient outward potassium current
      (I(to)) in normal and diseased myocardium.
AB  - G. Y. Oudit, Z. Kassiri, R. Sah, R. J. Ramirez, C. Zobel and P. H. Backx. The
      Molecular Physiology of the Cardiac Transient Outward Potassium Current (I(to))
      in Normal and Diseased Myocardium. Journal of Molecular and Cellular Cardiology
      (2001) 33, 851-872. The Ca(2+)-independent transient outward potassium current
      (I(to)) plays an important role in early repolarization of the cardiac action
      potential. I(to)has been clearly demonstrated in myocytes from different cardiac
      regions and species. Two kinetic variants of cardiac I(to)have been identified:
      fast I(to), called I(to,f), and slow I(to), called I(to,s). Recent findings
      suggest that I(to,f)is formed by assembly of K(v4.2)and/or K(v4.3)alpha pore
      forming voltage-gated subunits while I(to,s)is comprised of K(v1.4)and possibly
      K(v1.7)subunits. In addition, several regulatory subunits and pathways modulating
      the level and biophysical properties of cardiac I(to)have been identified.
      Experimental findings and data from computer modeling of cardiac action
      potentials have conclusively established an important physiological role of
      I(to)in rodents, with its role in large mammals being less well defined due to
      complex interplay between a multitude of cardiac ionic currents. A central and
      consistent electrophysiological change in cardiac disease is the reduction in
      I(to)density with a loss of heterogeneity of I(to)expression and associated
      action potential prolongation. Alterations of I(to)in rodent cardiac disease have
      been linked to repolarization abnormalities and alterations in intracellular
      Ca(2+)homeostasis, while in larger mammals the link with functional changes is
      far less certain. We review the current literature on the molecular basis for
      cardiac I(to)and the functional consequences of changes in I(to)that occur in
      cardiovascular disease.

PMID- 11343411
TI  - Molecular basis of the delayed rectifier current I(ks)in heart.
AB  - J. Kurokawa, H. Abriel and R. S. Kass. Molecular Basis of the Delayed Rectifier
      Current I(Ks)in Heart. Journal of Molecular and Cellular Cardiology (2001) 33,
      873-882. Electrical activity underlies the control of the frequency, strength,
      and duration of contraction of the heart. During the cardiac cycle, a regular
      rhythmic pattern must be established in time-dependent changes in ionic
      conductances in order to ensure events that underlie normal cardiac function.
      This pattern must be tightly regulated by sympathetic nervous activity to ensure
      a physiologically relevant relationship between diastolic filling and ejection
      times with variable heart rate. The duration of the ventricular action potential
      is controlled in part by a slowly activated potassium channel current, I(Ks). The
      molecular identity of the subunits that comprise the channels conducting this
      current is important, not only for understanding the fundamental mechanisms that
      control electrical activity in healthy individuals, but also for understanding
      the molecular basis of at least one inherited human disease, LQTS-1. This brief
      review summarizes key points of information regarding the molecular determinants
      of the activity of these channels, their relationship to human disease, and what
      is known, and yet to be discovered, about the molecular determinants of the
      regulation of this channel by sympathetic nervous activity.

PMID- 11343412
TI  - A deadly game of musical chairs: survival of cells transplanted for myocardial
      repair.

PMID- 11343413
TI  - Altered beta-adrenergic receptor gene regulation and signaling in chronic heart
      failure.
AB  - J. D. Port and M. R. Bristow. Altered Beta-adrenergic Receptor Gene Regulation
      and Signaling in Chronic Heart Failure. Journal of Molecular and Cellular
      Cardiology (2001) 33, 887-905. Beta adrenergic receptors (beta -ARs) are critical
      regulators of cardiac function in both normal and pathophysiological states.
      Under normal conditions, beta -ARs and their signaling pathways modulate both the
      rate and force of myocardial contraction and relaxation, allowing individuals to
      respond appropriately to physiological stress or exercise. However, in chronic
      heart failure, sustained activation of the beta -AR signaling pathways can have
      overtly negative biological consequences. This notion is reinforced by the
      positive outcomes of a number of clinical trials demonstrating the usefulness of
      beta-blocker therapy in chronic congestive heart failure. During the last few
      years, significant progress has been made in understanding the molecular
      biological basis of beta -AR function, both at the biochemical and genetic
      levels. In this review, the biological basis of adrenergic signaling and how this
      changes in heart failure is discussed. Aspects of adrenergic receptor
      pharmacology relevant to heart failure are reviewed, including the recently
      emerging differences described for beta(1)- v beta(2)-AR signaling pathways.
      Highlighting these differences is recent evidence that over-stimulation of the
      beta(1)-AR pathway in cardiac myocytes appears to be pro-apoptotic, whereas
      stimulation of the beta(2)-AR pathway may be anti-apoptotic. Overview of beta -AR
      gene regulation, transgenic models of beta -AR overexpression, and beta -AR
      polymorphisms as they relate to heart failure progression are also discussed.

PMID- 11343414
TI  - Cardiomyocyte grafting for cardiac repair: graft cell death and anti-death
      strategies.
AB  - M. Zhang, D. Methot, V. Poppa, Y. Fujio, K. Walsh and C. E. Murry. Cardiomyocyte
      Grafting for Cardiac Repair: Graft Cell Death and Anti-Death Strategies. Journal
      of Molecular and Cellular Cardiology (2001) 33, 907-921. Recent studies indicate
      that cardiomyocyte grafting forms new myocardium in injured hearts. It is
      unknown, however, whether physiologically significant amounts of new myocardium
      can be generated. Pilot experiments showed that death of grafted rat neonatal
      cardiomyocytes limited formation of new myocardium after acute cryoinjury. Time
      course studies showed that, at 30 min after grafting, only 1.8(+/-0.4)% of graft
      cells were TUNEL-positive. At 1 day, however, TUNEL indices increased to 32.1(+/
      3.5)% and remained high at 4 days, averaging 9.8(+/-3.8)%. By 7 days, TUNEL
      decreased to 1.0(+/-0.2)%. Electron microscopy revealed that dead cells had
      features of both irreversible ischemic injury and apoptosis. To test whether
      ischemia contributed to poor graft survival, grafts were placed into vascularized
      2-week-old cardiac granulation tissue or normal myocardium. TUNEL indices were
      reduced by 53% and 86%, respectively. Adenoviral infection of graft cells with
      the cytoprotective kinase Akt, or constitutively active Akt, reduced TUNEL
      indices by 31% and 40%, respectively, compared to beta -gal-transfected controls.
      Neither treatment reached statistical significance compared to untreated
      controls, however. Heat shock reduced cardiomyocyte death in vitro in response to
      serum deprivation, glucose depletion, and viral activation of the Fas death
      pathway. When cardiomyocytes were heat shocked prior to grafting, graft cell
      death in vivo was reduced by 54% at day 1. Therefore, high levels of
      cardiomyocyte death occur for at least 4 days after grafting into injured hearts,
      in large part due to ischemia. Death can be limited by activating the Akt pathway
      and even more effectively by heat shock prior to transplantation.

PMID- 11343415
TI  - Late sodium current is a novel target for amiodarone: studies in failing human
      myocardium.
AB  - V. A. Maltsev, H. N. Sabbah and A. I. Undrovinas. Late Sodium Current is a Novel
      Target for Amiodarone: Studies in Failing Human Myocardium. Journal of Molecular
      and Cellular Cardiology (2001) 33, 923-932. The authors recently reported the
      existence of a novel late Na(+)current (I(NaL)) in ventricular cardiomyocytes
      (VC) isolated from both normal and failing human hearts. Both in failing human
      and canine VC, partial block of I(NaL)normalized action potential (AP) duration
      and abolished early after depolarizations (EADs). The most recent computer
      simulation studies indicate a significant contribution of the persistent
      Na(+)current into the ion current balance on the plateau of VC AP as well as its
      important role in the dispersion of AP duration across the ventricular wall. The
      data thus indicate a possibility for I(NaL)to be a new therapeutic target. The
      present study tested a hypothesis that I(naL)could be a novel target for
      amiodarone (AMIO). Midmyocardial VC isolated from left ventricle of explanted
      failing human hearts were measured by a whole-cell clamp. I(NaL)was effectively
      blocked by AMIO in therapeutic concentrations, with IC(50)being 6.7+/-1.1 microM
      (mean+/-S.E.M., n=16 cells). At the same time, AMIO (5 microM ) produced almost
      no effect on the transient Na(+)current (IC(50)=87+/-28 microM, n=8). AMIO
      significantly shifted the steady-state inactivation (SSI) curve of I(NaL)towards
      more negative potentials and accelerated decay time course in a dose-dependent
      manner. At 5 microM, AMIO shifted SSI by 21+/-3 mV (n=7) and decreased the decay
      time constant from 0.67+/-0.05 s to 0.37+/-0.04 s (n=5, P<0.004). Evaluation of
      AMIO binding to different Na(+)channel (NaCh) states by means of mathematical
      models describing dose-dependent SSI shift and decay acceleration was consistent
      with an action that AMIO blocks NaCh preferentially in inactivated and activated
      states rather than in resting state. The authors conclude that the late
      Na(+)current is effectively blocked by AMIO and represents a new target for the
      drug in patients with chronic heart failure (HF).

PMID- 11343416
TI  - Retinoic acid attenuates inducible nitric oxide synthase (NOS2) activation in
      cultured rat cardiac myocytes and microvascular endothelial cells.
AB  - S. Grosjean, Y. Devaux, C. Seguin, C. Meistelman, F. Zannad, P.-M. Mertes, R. A.
      Kelly and D. Ungureanu-Longrois. Retinoic Acid Attenuates Inducible Nitric Oxide
      Synthase (NOS2) Activation in Cultured Rat Cardiac Myocytes and Microvascular
      Endothelial Cells. Journal of Molecular and Cellular Cardiology (2001) 33, 933
      945. The inducible NO synthase (NOS2) in cardiac tissue contributes to myocardial
      and coronary inflammation and dysfunction. Several natural (endogenous) hormones
      such as retinoic acid, the active metabolite of vitamin A, have the ability to
      attenuate NOS2 activation in inflammatory cells. The aim of this study was to
      investigate the effect of RA on NOS2 activation in cultured cardiac microvascular
      endothelial cells (CMEC) and adult rat ventricular myocytes (ARVM). CMEC were
      stimulated either with a combination of 10 microg/ml lipopolysaccharide (LPS) and
      50 IU/ml interferon- gamma (IFN- gamma) or with a combination of 1 ng/ml
      interleukin-1 beta (IL-1 beta)+IFN- gamma whereas ARVM were stimulated with 1
      ng/ml IL-1 beta and 50 IU/ml IFN- gamma in the absence or presence of all-trans
      retinoic acid (atRA). Activation of the NOS2 pathway was estimated by measurement
      of mRNA (Northern blot) and protein (Western blot) expression, enzyme activity by
      conversion of [(3)H]L -arginine to [(3)H]L -citrulline, and nitrite accumulation.
      NOS2 mRNA half-life was studied in CMEC and ARVM in the presence of actinomycin
      D. In CMEC and ARVM stimulated with a combination of LPS and/or cytokines, atRA
      (10(-6), 10(-5)M) significantly (P<0.05) attenuated NOS2 mRNA and protein
      expression, enzymatic activity and reduced supernatant nitrite concentration.
      Upon stimulation with LPS/IFN- gamma, atRA significantly decreased NOS2 mRNA half
      life. This was not seen after stimulation with IL-1 beta/IFN- gamma. These
      results document for the first time an effect of RA on NOS2 activation in cardiac
      cells. They may contribute to the characterization of the immunomodulatory
      effects of retinoids in myocardial and coronary inflammatory disorders.

PMID- 11343417
TI  - Cardioprotection by ischemic preconditioning preserves mitochondrial function and
      functional coupling between adenine nucleotide translocase and creatine kinase.
AB  - M. N. Laclau, S. Boudina, J. B. Thambo, L. Tariosse, G. Gouverneur, S. Bonoron
      Adele, V. A. Saks, K. D. Garlid and P. Dos Santos. Cardioprotection by Ischemic
      Preconditioning Preserves Mitochondrial Function and Functional Coupling Between
      Adenine Nucleotide Translocase and Creatine Kinase. Journal of Molecular and
      Cellular Cardiology (2001) 33, 947-956. This study investigates the effect of
      ischemic preconditioning on mitochondrial function, including functional coupling
      between the adenine nucleotide translocase and mitochondrial creatine kinase,
      which is among the first reactions to be altered in ischemia. Three groups of
      Langendorff-perfused rat hearts were studied: a control group, a group subjected
      to 30 min ischemia followed by 15 min reperfusion, and a group subjected to
      ischemic preconditioning prior to 30 min ischemia and 15 min reperfusion.
      Ischemic preconditioning significantly delayed the onset and amplitude of
      contracture during ischemia, decreased enzymatic release, and improved the
      recovery of heart contractile function after reperfusion. Mitochondrial function
      was assessed in permeabilized skinned fibers. The protective effect of
      preconditioning was associated with preservation of mitochondrial function, as
      evidenced by maintenance of the high K(1/2)for ADP in regulation of mitochondrial
      respiration and V(max)of respiration, the near absence of respiratory stimulation
      by exogenous cytochrome c, and preservation of functional coupling between
      mitochondrial creatine kinase and adenine nucleotide translocase. These data
      suggest that ischemic preconditioning preserves the structure-function of the
      intermembrane space, perhaps by opening the mitochondrial ATP-sensitive
      K(+)channel. The consequence is preservation of energy transfer processes from
      mitochondria to ATP-utilizing sites in the cytosol. Both of these factors may
      contribute to cardioprotection and better functional recovery of preconditioned
      hearts.

PMID- 11343418
TI  - Connexin37, not Cx40 and Cx43, is induced in vascular smooth muscle cells during
      coronary arteriogenesis.
AB  - W.-J. Cai, S. Koltai, E. Kocsis, D. Scholz, W. Schaper and J. Schaper.
      Connexin37, not Cx40 and Cx43, is Induced in Vascular Smooth Muscle Cells During
      Coronary Arteriogenesis. Journal of Molecular and Cellular Cardiology (2001) 33,
      957-967. The hypothesis that an altered expression of gap junction (GJ) proteins,
      connexin37 (Cx37), Cx40 and Cx43 will contribute to adaptive arteriogenesis was
      tested in growing coronary collateral vessels (CV) of the dog heart by
      immunoconfocal microscopy and transmission electron microscopy (TEM). We found
      that: (1) in the normal coronary system Cx37 and Cx40 were only expressed in
      endothelial cells (EC) from artery to capillary; (2) during collateral growth
      Cx37 was significantly induced in smooth muscle cells (SMC) from small-large
      arteries to precapillary arterioles (O=15 microm), while Cx40 was still only
      present in EC; (3) both homogeneous and heterogeneous distribution of Cx37 was
      observed in normal vessels (NV) and growing vessels (GV); (4) in mature vessels
      (MV), Cx37 was downregulated, similar to NV; (5) dual immunostaining revealed an
      inverse correlation between expression of Cx37 and desmin in GV occurring prior
      to downregulation of alpha-smooth actin and calponin; (6) Cx43 was undetectable
      in any vascular cells, both in NV and GV; (7) GJ were not found in SMC by TEM.
      Our data for the first time show the profile of connexin expression in the
      coronary system and provide evidence for existence of GJ proteins in capillaries.
      It is a novel finding that an altered expression of Cx37 is characteristic of
      adaptive arteriogenesis in the dog heart and may be used as a marker of vascular
      growth. Induced Cx37 may be an early signal indicating that SMC are responding to
      haemodynamic changes, i.e. increased shear stress.

PMID- 11343419
TI  - Combined angiotensin and endothelin receptor blockade attenuates adverse cardiac
      remodeling post-myocardial infarction in the rat: possible role of transforming
      growth factor beta(1).
AB  - A. Tzanidis, S. Lim, R. D. Hannan, F. See, A. M. Ugoni and H. Krum. Combined
      Angiotensin and Endothelin Receptor Blockade Attenuates Adverse Cardiac
      Remodeling Post-Myocardial Infarction in the Rat: Possible Role of Transforming
      Growth Factor beta(1). Journal of Molecular and Cellular Cardiology (2001) 33,
      969-981. Myocardial infarction (MI) is associated with activation of the
      vasoconstrictor peptides, angiotensin II (AngII) and endothelin-1 (ET-1), which
      are thought to contribute to adverse cardiac remodeling and dysfunction. The
      present study sought to determine whether combined AngII and ET receptor blockade
      improves cardiac remodeling over individual treatments in an experimental model
      of left ventricular myocardial infarction (LVMI) in the rat. Groups of eight
      female Sprague-Dawley rats were randomized at 24 h post-LVMI to 1 week treatment
      with either vehicle, an ET(A/B)receptor antagonist (bosentan), an AT(1)receptor
      antagonist (valsartan), or combined treatment. Vehicle-treated animals developed
      LV dysfunction with extensive accumulation of collagen type I and increased
      alpha(1)(I) procollagen mRNA compared to sham controls. Whilst individual
      receptor blockade with either bosentan or valsartan reduced LVEDP towards sham
      control levels, there were no significant changes to myocardial collagen
      deposition in comparison to vehicle. In contrast, improved ventricular function
      by combined treatment was associated with reduced type I collagen deposition
      within left ventricular non-infarct regions, as well as reduced peptide
      distribution and cardiac gene expression of the profibrogenic peptide,
      transforming growth factor beta(1)(TGF beta(1)). These data demonstrate that
      combined AngII and ET receptor blockade has beneficial effects on myocardial
      fibrogenesis over individual treatments during adverse cardiac remodeling early
      post-MI.

PMID- 11343420
TI  - Time course of the apoptotic cascade and effects of caspase inhibitors in adult
      rat ventricular cardiomyocytes.
AB  - K. Suzuki, S. Kostin, V. Person, A. Elsasser and J. Schaper. Time Course of the
      Apoptotic Cascade and Effects of Caspase Inhibitors in Adult Rat Ventricular
      Cardiomyocytes. Journal of Molecular and Cellular Cardiology (2001) 33, 983-994.
      Interpretation of the rate of apoptosis in diseased hearts is hampered by the
      fact that the time course of the apoptotic cascade in adult cardiomyocytes is
      largely unknown. Therefore, we established a standardized in vitro system,
      relevant to the in vivo situation of heart failure, using adult de- and
      redifferentiating cardiomyocytes to determine the time intervals necessary for
      the different steps of the apoptotic cascade to occur. Apoptosis was induced with
      0.1 mmol/l H(2)O(2)in adult rat cardiomyocytes 10 days in culture. Dosages >0.5
      mmol/l H(2)O(2)produced necrosis. Disruption of the mitochondrial membrane
      potential (Deltapsim) was the earliest sign of apoptosis and occurred at 2 h
      after H(2)O(2)exposure. The number of annexin V (translocation of
      phosphatidylserine) and PhiPhiLux (activation of caspase-3) positive cells
      significantly increased after 4 h and remained constant thereafter. Bcl-2 levels
      decreased. At 9 h, Bax expression was significantly elevated resulting in a
      reduced Bcl-2/Bax ratio. DNA fragmentation detected by TUNEL and ssDNA peaked at
      14 h, parallel to the appearance of apoptotic ultrastructural changes. Although
      DNA fragmentation was inhibited by zVAD-fmk, Ac-DEVD-CHO, zLEVD-fmk, these
      caspase inhibitors failed to inhibit disruption of Deltapsim and increased the
      number of necrotic cells. Catalase inhibited both apoptosis and necrosis. Our
      results indicate that the occurrence of the different steps of the apoptotic
      cascade is time-dependent and tightly regulated. Caspase inhibitors reduce
      apoptosis but increase the rate of necrosis, suggesting that the cells are
      destined to die upstream of the caspase step, i.e. by mitochondrial damage. These
      data provide the basis for the critical evaluation and interpretation of the
      occurrence of apoptosis in failing hearts.

PMID- 11343421
TI  - Renin expression at sites of repair in the infarcted rat heart.
AB  - Y. Sun, J. Zhang, J. Q. Zhang and K. T. Weber. Renin Expression at Sites of
      Repair in the Infarcted Rat Heart. Journal of Molecular and Cellular Cardiology
      (2001) 33, 995-1003. Angiotensin (Ang) II has autocrine and paracrine functions
      that contribute to structural cardiac remodeling by fibrous tissue following
      myocardial infarction (MI). The recruitment of angiotensin converting enzyme
      (ACE) and AngII receptors by inflammatory and fibroblast-like cells involved in
      tissue repair of the infarcted heart is now well established. On the other hand,
      the temporal and spatial response and cellular source of renin in infarcted
      hearts have not been fully elucidated. The relationship between renin synthesis
      and circulating renin activity have likewise not been addressed. The present
      study sought to assess the cellular source, spatial distribution and temporal
      response of renin expression and synthesis in the rat heart following anterior
      transmural MI, and to determine its relationship to circulating renin activity.
      At day 3 and weeks 1, 2, 3 and 4 following left coronary artery ligation, the
      localization and optical density of cardiac renin mRNA was detected by
      quantitative in situ hybridization; cardiac and circulating renin activity was
      measured by radioimmunoassay; cells expressing cardiac renin were detected by
      immunohistochemistry; and injury/repair was assessed by hematoxylin/eosin and
      collagen-specific picrosirius red staining. Unoperated rats served as normal
      controls. The authors found: (1) renin mRNA and activity were not detected in
      either normal control or non-infarcted myocardium, but were expressed at the site
      of infarction and other sites of repair involving visceral pericardium and
      endocardium of interventricular septum at all time points; (2) cells expressing
      renin at day 3 and weeks 1 and 2 were predominantly macrophages, while at weeks 3
      and 4, they were primarily myofibroblasts; (3) renin activity in the infarcted
      myocardium rose progressively over the course of 4 weeks; and (4) circulating
      renin activity was significantly increased at day 3 and week 1, reached a peak at
      week 2, declined at week 3 and returned to normal levels at week 4. Thus, renin
      expression and activity appear at sites of repair in the infarcted rat heart on
      day 3 and rise progressively thereafter over 4 weeks, independent of circulating
      renin. Several types of cells are responsible for renin synthesis at these sites;
      primarily macrophages during the inflammatory phase of repair, and myofibroblasts
      during the subsequent fibrogenic phase. Cardiac renin production following MI
      contributes to local AngII generation that regulates tissue repair and structural
      remodeling following MI.

PMID- 11343422
TI  - SERCA2A overexpression decreases the incidence of aftercontractions in adult
      rabbit ventricular myocytes.
AB  - K. Davia, E. Bernobich, H. K. Ranu, F. del Monte, C. M. N. Terracciano, K. T.
      MacLeod, D. L. Adamson, B. Chaudhri, R. J. Hajjar and S. E. Harding. SERCA2a
      Overexpression Decreases the Incidence of Aftercontractions in Adult Rabbit
      Ventricular Myocytes. Journal of Molecular and Cellular Cardiology (2001) 33,
      1005-1015. Slow relaxation and poor contractile response to increasing
      stimulation frequency in failing human heart have been strongly linked to a
      decrease in the activity of the sarcoplasmic reticulum (SR) Ca(2+)-ATPase
      (SERCA2a). Restoration of SERCA2a levels using gene transfer has beneficial
      effects on contractile function but, like beta -adrenoceptor stimulation, could
      potentially produce excess SR Ca(2+), arrhythmias and cell death. We have
      examined the effects of SERCA2a overexpression in adult rabbit cardiac myocytes,
      and compared changes in relaxation with those following beta -adrenoceptor
      stimulation. Myocytes were infected with an adenovirus carrying both SERCA2a and
      green fluorescent protein (GFP) for positive identification of infected cells.
      Myocyte survival was significantly enhanced in the infected cultures. There was a
      reduction in both time-to-peak contraction and time-to-50% relaxation (R50) 48 h
      after infection. Time-to-90% relaxation (R90) was particularly improved (non
      infected 516+/-41 ms, AD.SERCA2a-GFP 230+/-23 ms, n=7 preparations, P<0.001).
      There was also a decreased incidence of aftercontractions in Ad.SERCA2a-GFP
      infected myocytes (21+/-5%v 41+/-4% in controls, P<0.01). This contrasts with
      beta -adrenoceptor stimulation, which reduced R50 but prolonged R90 by 158+/-76
      ms (P<0.02, n=16). At higher stimulation frequencies (2-3 Hz) contraction
      amplitude and SR calcium content were increased and diastolic contracture was
      reduced following SERCA2a overexpression. Overall, increasing levels of SERCA2a
      resulted in an improvement in systolic and diastolic function and a reduction in
      cell death and arrhythmic aftercontractions. SERCA2a overexpression therefore
      lacks the detrimental effects associated with some other inotropic interventions.

PMID- 11343423
TI  - Pyk2 expression and phosphorylation in neonatal and adult cardiomyocytes.
AB  - A. L. Bayer, A. G. Ferguson, P. A. Lucchesi and A. M. Samarel. PYK2 Expression
      and Phosphorylation in Neonatal and Adult Cardiomyocytes. Journal of Molecular
      and Cellular Cardiology (2001) 33, 1017-1030. Proline-rich tyrosine kinase (PYK2)
      is a Ca(2+)-dependent, non-receptor protein tyrosine kinase involved in growth
      factor signaling. Although PYK2 is expressed in a variety of tissues, it has not
      yet been identified in cardiac muscle. Therefore, immunocytochemical and Western
      blotting techniques were used to examine PYK2 expression and phosphorylation in
      neonatal and adult rat ventricular cardiomyocytes (NRVM and ARVM, respectively).
      PYK2 concentration was much greater in neonatal, than in adult ventricular tissue
      and cardiomyocytes. In cultured cells, PYK2 expression was highly dependent on
      [Ca(2+)](i)transients and contractile activity. Non-contracting, low-density NRVM
      in serum-free culture expressed very low levels of PYK2, while high-density,
      spontaneously contracting NRVM showed a approximately 12-fold increase in PYK2
      expression. Conversely, high-density NRVM treated with nifedipine (10 microM, 48
      h) to block spontaneous [Ca(2+)](i)transients and contractile activity resulted
      in a 2.6-fold decrease in PYK2 levels. Similarly, overnight culture of quiescent
      ARVM markedly reduced PYK2 levels. Chronic treatment (48 h) of cultured NRVM with
      the hypertrophic agonist endothelin-1 (ET) (10-300 n M) did not significantly
      increase PYK2 levels, but strongly shifted the ratio of phosphorylated to total
      PYK2, indicating that PYK2 phosphorylation accompanies cardiomyocyte hypertrophy.
      Endothelin-1 also acutely activated PYK2 in both cultured NRVM, and in freshly
      isolated ARVM. These results suggest that PYK2 is involved in the generation of
      certain aspects of cardiomyocyte hypertrophy.

PMID- 11343424
TI  - The enhanced contractility of the phospholamban-deficient mouse heart persists
      with aging.
AB  - J. P. Slack, I. L. Grupp, R. Dash, D. Holder, A. Schmidt, M. J. Gerst, T. Tamura,
      C. Tilgmann, P. F. James, R. Johnson, A. M. Gerdes and E. G. Kranias. The
      Enhanced Contractility of the Phospholamban-deficient Mouse Heart Persists with
      Aging. Journal of Molecular and Cellular Cardiology (2001) 33, 1031-1040.
      Phospholamban ablation in the mouse is associated with significant increases in
      cardiac contractility. To determine whether this hyperdynamic function persists
      through the aging process, a longitudinal examination of age-matched
      phospholamban-deficient and wild-type mice was employed. Kaplan-Meier survival
      curves indicated no significant differences between phospholamban-deficient and
      wild-type mice over the first year. Examination of cardiac function revealed
      significant increases in the rates of contraction (+dP/dt) and relaxation (
      dP/dt) in phospholamban-deficient hearts compared with their wild-type
      counterparts at 3, 6, 12, 18 and 24 months of age. Quantitative immunoblotting
      indicated that the expression levels of the sarcoplasmic reticulum Ca(2+)-ATPase
      were not altered in wild-type hearts, while they were significantly decreased at
      12 months (40%) and 18 months (20%) in phospholamban-deficient hearts. These
      findings on the persistence of hyperdynamic cardiac function over the long term
      suggest that phospholamban may constitute an important target for treatment in
      heart disease.

PMID- 11343425
TI  - Sarcolemmal and mitochondrial K(atp)channels mediate cardioprotection in
      chronically hypoxic hearts.
AB  - X. Kong, J. S. Tweddell, G. J. Gross and J. E. Baker. Sarcolemmal and
      Mitochondrial K(ATP)Channels Mediate Cardioprotection in Chronically Hypoxic
      Hearts. Journal of Molecular and Cellular Cardiology (2001) 33, 1041-1045.
      Hypoxia from birth increases the resistance of the isolated neonatal heart to
      ischemia. We determined if increased resistance to ischemia was due to activation
      of sarcolemmal or mitochondrial K(ATP)channels. Rabbits (n=8/group) were raised
      from birth in a normoxic (F(I)O(2)=0.21) or hypoxic (F(I)O(2)=0.12) environment
      for 8-10 days and the heart perfused with Krebs-Henseleit bicarbonate buffer. A
      mitochondrial-selective K(ATP)channel blocker 5-hydroxydecanoate (5-HD) (300
      micromol/l) or a sarcolemmal-selective K(ATP)channel blocker HMR 1098 (30
      micromol/l) were added alone or in combination for 20 min prior to a global
      ischemic period of 30 min, followed by 35 min reperfusion. Recovery of
      ventricular developed pressure was higher in chronically hypoxic than normoxic
      hearts. 5-HD and HMR 1098 partially reduced the cardioprotective effect of
      chronic hypoxia, but had no effect in normoxic hearts. The combination of 5-HD
      and HMR 1098 abolished the cardioprotective effect of chronic hypoxia. We
      conclude that both sarcolemmal and mitochondrial K(ATP)channels contribute to
      cardioprotection in the chronically hypoxic heart.

PMID- 11343427
TI  - Cell inactivation by ionizing particles and the shapes of survival curves.
AB  - Recent experiments concerning the survival of monolayer cells irradiated by
      different parts of ion Bragg peaks opened a way to a deeper mechanistic
      understanding of cell inactivation. A new theoretical formula for survival curves
      has been derived reflecting two basic phases of the given mechanism, i.e. energy
      transfer to a cell nucleus and subsequent biological effect (depending on the
      amount of imparted energy). The survival ratio for a given dose has been
      expressed as a function of inactivation probabilities of individual cells after
      different numbers of nucleus hits (a given amount of energy being transferred to
      a cell nucleus in each ion traversal). Having used the experimental data for V79
      cells irradiated by protons, deuterons and helium ions in different parts of
      Bragg peaks preliminary values of these inactivation probabilities for individual
      cells at different LET values have been established.

PMID- 11343428
TI  - Modelled influences of non-exchanging trichomes on leaf boundary layers and gas
      exchange.
AB  - The two main resistances in the exchange of gases between plants and the
      atmosphere are stomatal and boundary layer resistances. We modeled boundary layer
      dynamics over glabrous and pubescent leaves (assuming non-exchanging trichomes)
      with leaf lengths varying from 0.01 to 0.2 m, and windspeeds of 0.1-5.0 m x s(
      1). Results from theoretical and semi-empirical formulae were compared. As
      expected, boundary layer thickness decreased with decreasing leaf length and
      increasing windspeed. The presence of trichomes increased leaf surface roughness,
      resulting in lowered Reynolds numbers at which the boundary layer became
      turbulent. This effect is especially important at low windspeeds and over small
      leaves, where the Reynolds number over glabrous surfaces would be low. We derived
      a new simple dimensionless number, the trip factor, to distinguish field
      conditions that would lead to a turbulent boundary layer based on the influence
      of trichomes. Because modeled rates of CO2 and H2O(v) exchange over turbulent
      boundary layers are one or more orders of magnitude faster than over laminar
      boundary layers, a turbulent boundary layer may lead to increased carbon uptake
      by plants. The biological trade-off is potentially increased transpirational
      water loss. However, in understory habitats characterized by low windspeeds, even
      a few trichomes may increase turbulence in the boundary layer, thus facilitating
      photosynthetic gas exchange. Preliminary field data show that critical trip
      factors are exceeded for several plant species, both in understory and open
      habitats.

PMID- 11343429
TI  - Do insects use templates or parameters for landmark navigation?
AB  - As an explanation for the landmark navigation abilities of insects, the template
      hypothesis is currently clearly dominating the parameter hypothesis. In a series
      of computer simulations, this paper investigates the conspicuous behavior of
      desert ants in experimental setups with expanded landmark arrays. It is shown
      that a parameter-based model accounts much better for the data than different
      template models.

PMID- 11343430
TI  - Patterns of age-specific means and genetic variances of mortality rates predicted
      by the mutation-accumulation theory of ageing.
AB  - A general quantitative genetic model of mutations with age-specific deleterious
      effects is developed. It is shown that, for the simplest case of a species with
      age-independent reproductive rates and extrinsic adult mortality rates, and no
      pleiotropic effects of age-specific mutations, exponential increases with age of
      both the mean and additive genetic variance of age-specific mortality rates are
      expected. Models where age-specific mutations have pleiotropic effects on
      mortality that extend either throughout adult life, or are confined to juvenile
      stages, produce equilibria with exponential increases in the mean and additive
      variance of mortality rates during much of adult life. However, the rates of
      increase diminish late in life, and can even become zero. Predictions concerning
      the additive genetic correlations in mortality rates between different ages are
      also developed. The predictions of the models are compared with data on humans
      and Drosophila.

PMID- 11343431
TI  - Dynamics of marine sessile organisms with space-limited growth and recruitment:
      application to corals.
AB  - We study a model for the community dynamics of marine sessile organisms with
      space limitation both in recruitment and in growth. We consider an open
      population in which recruits are supplied from a pelagic pool of larvae produced
      by adults in distant habitats. Assumptions are: the larval settlement rate is
      proportional to the amount of free space and to the abundance of larvae in the
      water column. The growth rate of settled individuals increases with the fraction
      of free space within the local habitat. We study the competition between two
      morphotypes with different rates of recruitment, growth, and mortality. When
      adult mortality is low, following a major disturbance that creates bare patch,
      the space is quickly filled by larval recruitment and adult growth. Then the
      morphotype composition changes slowly and converges to the equilibrium that is
      strongly affected by mortality. We also examine several other limiting cases in
      which one of the three demographic processes occurs either very slowly or very
      quickly. Based on the model behavior, we discuss the possible factors responsible
      for the spatial variation in the morphotype composition observed in coral
      communities. The dominance of branching corals in protected sites can be
      explained by their faster growth than tabular corals. The dominance of tabular
      corals in exposed sites can be explained either by lower mortality or by faster
      recruitment than branching corals.

PMID- 11343432
TI  - Directed motion in the sea: efficient swimming by reef fish larvae.
AB  - Directed motion of marine organisms is examined with a focus on efficient
      behaviour, where efficient swimming minimizes either energetic expenditure or
      transit time. The swimming behaviour of late pelagic stage reef fish larvae is
      modelled to illustrate relevant concepts. To swim efficiently in the sea, an
      organism should exploit current-driven movements of the medium. Favourable
      currents should be ridden and unfavourable currents avoided. Relatively short
      movements to control advection can have a greater effect than longer swimming
      bouts used for independent horizontal locomotion. If larvae exploit the vertical
      structure of the water column, then the extent to which they can influence their
      dispersal will be substantially increased.

PMID- 11343433
TI  - The effect of tissue-specific growth patterns of target stem cells on the
      spectrum of tumours resulting from multistage tumorigenesis.
AB  - A multistage mathematical model of tumorigenesis has been developed to explore
      the effects of target cell growth pattern on the proportions of tumours deriving
      from different tissues (the tumour spectrum). Analytical modelling techniques
      have shown that the effect of the target cell growth pattern on the tumour
      spectrum also depends on the number of stages (gene mutations) necessary for
      malignant change in cells of each tissue type. This suggests the existence of
      temporal "windows of opportunity" for tumours of different types in relation to
      stage number and growth kinetics. Models of this kind are applicable to cancer
      prone transgenic (e.g. p53 deficient) mice, where homozygotes and heterozygotes
      differ in one carcinogenic stage, and differ also in the spectrum of tumours
      observed. Generally, tumours deriving from target stem cells which are
      developmentally short-lived will arise more frequently in homozygotes than
      heterozygotes. Such models may also be applicable to human syndromes (e.g. Li
      Fraumeni) in which susceptibility to cancer is inherited.

PMID- 11343434
TI  - Geometrical constraints on the development of a diatom.
AB  - In a plane hexagonal array of pores such as occurs in Thalassiosira oestrupii and
      other related species of marine diatom, the presence of a single, exceptional
      pore near the center of the array can cause the distortion in the pattern in such
      a way that the pores tend to diminish in diameter D with increasing distance R
      from the center. By a simple mathematical argument it is shown that for large
      values of R/D the pore diameter D varies as R(-1/6). This decrease in pore
      diameter with distance may have some developmental consequences. The law is
      generalized to other types of pattern. The second type of constraint, related to
      the presence of outer boundaries, is also discussed.

PMID- 11343435
TI  - Progression of heterogeneous breast tumors.
AB  - Two possible pathways of breast tumor progression were investigated by searching
      for values of transition rates that could reproduce the clinically observed co
      occurrence frequencies of grades of ductal carcinoma in situ and grades of
      invasive ductal carcinoma in heterogeneous tumors. Two different pathways were
      analysed, a linear pathway with seven parameters, and a nonlinear pathway with
      three parameters. In each pathway ductal carcinoma in situ (DCIS) is a progenitor
      of invasive carcinoma (IDC). In the linear pathway breast tumor progression is
      along increasing grades: DCIS 1-DCIS 2-DCIS 3-IDC 1-IDC 2-IDC 3. In the nonlinear
      pathway progression of DCIS and progression of IDC can proceed in parallel steps,
      and in addition, with transitions from each grade of DCIS to a corresponding
      grade of IDC. The biological pathways were interpreted mathematically as
      compartment models with transition rates between stages in an explicit series of
      coupled differential equations. Two methods were used to search for transition
      rates that could reproduce the observed co-occurrence frequencies, a limited
      empirical search and an extensive genetic algorithmic search. Neither search
      method, with either pathway, could find a combination of transition rates that
      would reproduce the set of observed co-occurrence frequencies. We conclude that
      neither the linear pathway, nor the nonlinear pathway considered here, is an
      adequate description of progression in heterogeneous breast tumors. This
      quantitative investigation lends support to previous evidence from histopathology
      and molecular biology that the grades of DCIS and IDC seen together in
      heterogeneous breast tumors may not be obligate steps in tumor progression.

PMID- 11343436
TI  - The role of hyaluronan in the pulmonary alveolus.
AB  - The duplex nature of the lining of the pulmonary alveolus has long been
      appreciated. It appears that surfactant is present at the interface with air
      where it prevents the collapse of the alveolus by lowering surface tension and
      that the surfactant rests on an aqueous subphase. This subphase has enough
      structure to form a smooth, continuous surface over the projections of the
      epithelial cells and because of its hydrophilic nature it attracts the polar
      heads of surfactant phospholipids. The chemical composition of the subphase has
      not been addressed. Type II cells in the wall of the alveolus are specialized to
      produce surfactant and they also secrete hyaluronan (hyaluronic acid) into the
      subphase. In solution, molecules of hyaluronan appear to be flexible coils which
      self-aggregate. The resulting solutions are quite viscous and exhibit non
      Newtonian behavior. Hyaluronan binds to cell surface receptors and to proteins in
      the extracellular matrix. The networks formed with self-aggregated hyaluronan
      with or without proteins create gels whose properties depend largely upon the
      molecular weight of the hyaluronan and its concentration. Hyaluronan is also
      known to interact with phospholipids and has hydrophobic regions which could bind
      to the hydrophobic surfactant proteins B and C. The working hypothesis presented
      herein states that hyaluronan interacts with itself and with proteins in the
      subphase to form a hydrophilic gel. At the epithelial cell layer the components
      are concentrated due to tethered HA molecules and the gel smooths over cell
      projections. At the air interface the components are so dilute that a layer which
      is essentially water is present. The surfactant phospholipids spread on the
      water. Direct interactions of HA and surfactant phospholipids may also occur and
      contribute to the stability of the surfactant layer.

PMID- 11343437
TI  - Is it time for a new approach to the initial treatment of hypertension?

PMID- 11343438
TI  - Epidemiologic review of the calcium channel blocker drugs. An up-to-date
      perspective on the proposed hazards.
AB  - In the setting of soaring popularity, postmarketing studies of calcium channel
      blockers came to suggest an increase in a variety of major adverse end points.
      The evidence, however, was largely observational, and large-scale trials capable
      of addressing the concerns were wanting. Clinical trials now support the safety
      and efficacy of the long-acting dihydropyridines for patients with both
      uncomplicated and diabetic hypertension, although conventional therapies and, in
      the latter case, angiotensin-converting enzyme inhibitors have superior proof of
      benefit. By contrast, short-acting dihydropyridines should be avoided. In the
      acute coronary syndromes, beta-blockers remain the treatment of choice; the
      evidence for nondihydropyridines remains inconclusive. Stable angina calls for
      beta-blockers as first-line therapy and nondihydropyridines as second-line
      therapy, whereas in ventricular dysfunction, safety data for nondihydropyridines
      are lacking. Initial reports of cancer, bleeding, and suicide have been
      contradicted by subsequent data, making the associations uncertain or unlikely.
      Remaining questions await completion of ongoing trials to better define the
      indications for these agents.

PMID- 11343439
TI  - A review of the evidence for the use of phytoestrogens as a replacement for
      traditional estrogen replacement therapy.
AB  - Estrogen replacement therapy (ERT) is recommended for postmenopausal women
      primarily for reduction of menopausal symptoms and prevention of osteoporosis and
      cardiovascular disease. However, only 35% to 40% of women ever start ERT, and
      many do not continue it. One of the reasons women are reluctant to receive
      postmenopausal ERT is that they perceive prescription estrogens as being
      "unnatural." Because of this, there is increasing interest in the use of plant
      derived estrogens, also known as phytoestrogens. This article reviews the
      evidence for the potential of phytoestrogens, either in dietary or supplemental
      form, to replace traditional forms of ERT. A comprehensive search of the English
      language literature identified more than 1000 articles published in the past 30
      years about phytoestrogens. In total, 74 studies were selected for inclusion in
      this review based on relevance, inclusion of human subjects wherever possible,
      and study design. The studies examine phytoestrogens' inhibition of the growth of
      cancer cell lines in vitro and in animals. They also look at the role of
      phytoestrogens in the reduction of cholesterol levels, and the use of one
      phytoestrogen derivative, ipriflavone, in the prevention of osteoporosis. Some
      small studies examine the role of phytoestrogens in the prevention of menopausal
      symptoms. Evidence for the potential health benefits of phytoestrogens is
      increasing. However, the clinically proven health benefits of prescribed ERT far
      outweigh those of phytoestrogens. Therefore, there is insufficient evidence to
      recommend the use of phytoestrogens in place of traditional ERT, or to make
      recommendations to women about specific phytoestrogen products.

PMID- 11343440
TI  - Physical inactivity and short-term all-cause mortality in adults with chronic
      disease.
AB  - OBJECTIVE: To ascertain the relationship of physical inactivity and short-term
      all-cause mortality in a prospective cohort of randomly selected managed care
      organization members aged 40 years and older who have multiple chronic diseases.
      METHODS: Clinical databases were used to identify all health plan members aged 40
      years and older with 2 or more chronic health conditions (hypertension, coronary
      heart disease, diabetes mellitus, or dyslipemia) in 1994. A random sample of 2336
      members was surveyed by mail and telephone interview regarding their health
      related behaviors. Survey data were linked to mortality data from the 1995 to
      1997 Minnesota Death Index. Cox proportional hazards regression was used to
      ascertain the association between physical inactivity and subsequent all-cause
      mortality, adjusting for potential confounders. RESULTS: Members who reported
      less than 30 minutes a week of physical activity at baseline had a subsequent
      mortality risk ratio of 2.82 (P<.001) vs those with 30 or more minutes of
      physical activity a week. Increased mortality risk persisted (mortality risk
      ratio, 2.15; P<.001) after adjustments for age, sex, current smoking, functional
      impairment, and comorbidity score. CONCLUSIONS: In adults with chronic diseases,
      the physically inactive had higher observed mortality within a 42-month period.
      If physical inactivity reflects an independent mortality risk, efforts to
      maintain physical activity in such patients may yield significant clinical
      benefits within a short period. By contrast, if inactivity is primarily a proxy
      for other factors that elevate mortality risks, a simple physician inquiry
      regarding inactivity may help to identify patients at risk of death.

PMID- 11343441
TI  - Association between blood pressure level and the risk of myocardial infarction,
      stroke, and total mortality: the cardiovascular health study.
AB  - BACKGROUND: Recent reports have drawn attention to the importance of pulse
      pressure as a predictor of cardiovascular events. Pulse pressure is used neither
      by clinicians nor by guidelines to define treatable levels of blood pressure.
      METHODS: In the Cardiovascular Health Study, 5888 adults 65 years and older were
      recruited from 4 US centers. At baseline in 1989-1990, participants underwent an
      extensive examination, and all subsequent cardiovascular events were ascertained
      and classified. RESULTS: At baseline, 1961 men and 2941 women were at risk for an
      incident myocardial infarction or stroke. During follow-up that averaged 6.7
      years, 572 subjects had a coronary event, 385 had a stroke, and 896 died. After
      adjustment for potential confounders, systolic blood pressure (SBP), diastolic
      blood pressure (DBP), and pulse pressure were directly associated with the risk
      of incident myocardial infarction and stroke. Only SBP was associated with total
      mortality. Importantly, SBP was a better predictor of cardiovascular events than
      DBP or pulse pressure. In the adjusted model for myocardial infarction, a 1-SD
      change in SBP, DBP, and pulse pressure was associated with hazard ratios (95%
      confidence intervals) of 1.24 (1.15-1.35), 1.13 (1.04-1.22), and 1.21 (1.12
      1.31), respectively; and adding pulse pressure or DBP to the model did not
      improve the fit. For stroke, the hazard ratios (95% confidence intervals) were
      1.34 (1.21-1.47) with SBP, 1.29 (1.17-1.42) with DBP, and 1.21 (1.10-1.34) with
      pulse pressure. The association between blood pressure level and cardiovascular
      disease risk was generally linear; specifically, there was no evidence of a J
      shaped relationship. In those with treated hypertension, the hazard ratios for
      the association of SBP with the risks for myocardial infarction and stroke were
      less pronounced than in those without treated hypertension. CONCLUSION: In this
      population-based study of older adults, although all measures of blood pressure
      were strongly and directly related to the risk of coronary and cerebrovascular
      events, SBP was the best single predictor of cardiovascular events.

PMID- 11343442
TI  - An evidence-based assessment of federal guidelines for overweight and obesity as
      they apply to elderly persons.
AB  - BACKGROUND: The US Clinical Guidelines on the Identification, Evaluation, and
      Treatment of Overweight and Obesity in Adults set the body mass index (BMI;
      weight in kilograms divided by the square of height in meters) of 25 as the upper
      limit of ideal weight for all adults regardless of age. However, the prognostic
      importance of overweight and obesity in elderly persons (>/=65 years) is
      controversial. We sought to analyze the guidelines in the context of currently
      available evidence that is relevant to older adults. METHODS: We searched MEDLINE
      for all English-language studies of the association between BMI and all-cause or
      cardiovascular mortality or coronary heart disease events from January 1966
      through October 1999. Additional pertinent articles were identified through
      bibliographies of the MEDLINE articles. We selected studies for detailed review
      if they reported on the association between BMI and mortality for nonhospitalized
      subjects who were 65 years or older and had been followed up for at least 3
      years. We controlled for age, smoking, and baseline health status. Of the 444
      screened articles, 13 were selected to assess the guidelines. We extracted
      information regarding publication year, study design, population, recruitment
      period, follow-up duration, number of subjects, sex, age range, inclusion and
      exclusion criteria, and statistical models, including variables and end points.
      RESULTS: These data do not support the BMI range of 25 to 27 as a risk factor for
      all-cause and cardiovascular mortality among elderly persons. The results were
      not substantially different for men and women. Most studies showed a negative or
      no association between BMI and all-cause mortality. Three studies indicated
      overweight (BMI >/=27) as a significant prognostic factor for all-cause and
      cardiovascular mortality among 65- to 74-year-olds, and one study showed a
      significant positive association between overweight (BMI >/=28) and all-cause
      mortality among those 75 years or older. Higher BMI values were consistent with a
      smaller relative mortality risk in elderly persons compared with young and middle
      aged populations. CONCLUSIONS: Federal guideline standards for ideal weight (BMI
      18.7 to <25) may be overly restrictive as they apply to the elderly. Studies do
      not support overweight, as opposed to obesity, as conferring an excess mortality
      risk. Future guidelines should consider the evidence for specific age groups when
      establishing standards for healthy weight.

PMID- 11343443
TI  - Prevalence of high blood pressure and elevated serum creatinine level in the
      United States: findings from the third National Health and Nutrition Examination
      Survey (1988-1994).
AB  - BACKGROUND: The prevalence and incidence of end-stage renal disease in the United
      States are increasing, but milder renal disease is much more common and may often
      go undiagnosed and undertreated. METHODS: A cross-sectional study of a
      representative sample of the US population was conducted using 16 589 adult
      participants aged 17 years and older in the Third National Health and Nutrition
      Examination Survey (NHANES III) conducted from 1988 to 1994. An elevated serum
      creatinine level was defined as 141 micromol/L or higher (>/=1.6 mg/dL) for men
      and 124 micromol/L or higher (>/=1.4 mg/dL) for women (>99th percentile for
      healthy young adults) and was the main outcome measure. RESULTS: Higher systolic
      and diastolic blood pressures, presence of hypertension, antihypertensive
      medication use, older age, and diabetes mellitus were all associated with higher
      serum creatinine levels. An estimated 3.0% (5.6 million) of the civilian,
      noninstitutionalized US population had elevated serum creatinine levels, 70% of
      whom were hypertensive. Among hypertensive individuals with an elevated serum
      creatinine level, 75% received treatment. However, only 11% of all individuals
      with hypertension had their blood pressure reduced to lower than 130/85 mm Hg
      (the Sixth Report of the Joint National Committee on Detection, Evaluation, and
      Treatment of High Blood Pressure recommendation for hypertensive individuals with
      renal disease); 27% had a blood pressure lower than 140/90 mm Hg. Treated
      hypertensive individuals with an elevated creatinine level had a mean blood
      pressure of 147/77 mm Hg, 48% of whom were prescribed one antihypertensive
      medication. CONCLUSION: Elevated serum creatinine level, an indicator of chronic
      renal disease, is common and strongly related to inadequate treatment of high
      blood pressure.

PMID- 11343444
TI  - Pattern of primary resistance of Helicobacter pylori to metronidazole or
      clarithromycin in the United States.
AB  - BACKGROUND: Therapy for Helicobacter pylori is generally empiric despite the fact
      that resistance to metronidazole and clarithromycin compromise therapeutic
      efficacy. The aim of this study was to aid clinicians in choosing a course of
      therapy for H pylori infection in the United States. METHODS: The frequency of
      primary clarithromycin and metronidazole resistance among H pylori isolated from
      patients enrolled in US-based clinical trials between 1993 and 1999 was reviewed
      in relation to patient age, sex, region of the United States, and test method
      (Etest and 2 agar dilution procedures). RESULTS: Clarithromycin and metronidazole
      resistance rates were based on the results of 3439 pretreatment Etest
      determinations and 3193 agar dilution determinations. Sex and age were available
      on 900 and 823 individuals, respectively. Metronidazole resistance was 39% by
      Etest and 21.6% by agar dilution (P<.001). Clarithromycin resistance was 12% by
      Etest and 10.6% by agar dilution. Amoxicillin or tetracycline resistance was
      rare. Metronidazole and clarithromycin resistance was more common in women than
      men (eg, 34.7% vs 22.6% for metronidazole and 14.1% vs 9.7% for clarithromycin (P
      =.01 and P =.06, respectively). Antibiotic resistance increased gradually up to
      age 70 years, then declined significantly (P<.05) regardless of test method.
      Regional differences in antimicrobial resistance did not occur. CONCLUSIONS:
      While age and sex had significant effects on resistance rates, regional
      differences were not present. The high prevalence of resistance to metronidazole
      and clarithromycin may soon require the performance of antimicrobial
      susceptibility testing of H pylori isolates prior to initiating treatment.

PMID- 11343445
TI  - Assessing use of primary health care services by very low-income adults in a
      managed care program.
AB  - OBJECTIVE: To assess the effect of providing free health care services to low
      income adults. METHODS: We measured access to primary care services by enrollees
      with 4 chronic medical conditions in the General Relief Health Care Program
      (GRHCP), a program designed for adults receiving General Relief (GR). Implemented
      by the Los Angeles County Health Department in October 1995, the GRHCP is
      composed of private and public health care facilities. As adults registered for
      GR, they were asked to complete a baseline health survey, were enrolled in the
      GRHCP, and assigned a health care provider. A total of 8520 surveys were
      completed between September and November 1996 (98% response rate). The analyses
      of this article are limited to individuals (N = 2164) who reported a history of
      hypertension, diabetes mellitus, a nonresolving cough, or substance dependence.
      We reviewed medical records to determine whether new GR recipients had visited
      their designated GRHCP provider within 4 months of enrollment and used
      multivariate logistic regression to assess the effect of individual patient
      factors on the use of free health care. RESULTS: A total of 17% of individuals
      visited their assigned GRHCP provider within 4 months of enrollment. In
      multivariate analysis, patients were more likely to have made a visit if they
      were younger than 50 years, were female, were Asian/Pacific Islander, reported
      needing to see a physician, or had seen a physician within 12 months.
      CONCLUSIONS: It is not sufficient to merely supply the name and address of a
      health care provider to this population. More aggressive efforts should be
      attempted to increase utilization of services for patients with medical
      conditions responsive to ambulatory care.

PMID- 11343446
TI  - Bleeding associated with doxycycline and warfarin treatment.

PMID- 11343447
TI  - Survival after the resuscitation.

PMID- 11343449
TI  - Periodontal disease, C-reactive protein, and ischemic stroke.

PMID- 11343452
TI  - Cost-effectiveness of antiplatelet therapies.

PMID- 11343450
TI  - Baseline rates of disease may account for some arrhythmia risk.

PMID- 11343453
TI  - Is treatment with aspirin combined with dipyridamole really more cost-effective
      than aspirin alone?

PMID- 11343454
TI  - Methicillin-susceptible Staphylococcus aureus: believe it, or not.

PMID- 11343456
TI  - Studies on recognition of dementia by primary care physicians are inconsistent.

PMID- 11343459
TI  - A piece of my mind: familial hepatitis.

PMID- 11343460
TI  - Clinical xenotransplantation.

PMID- 11343461
TI  - At Pennsylvania Hospital, 250 years of care.

PMID- 11343462
TI  - Researchers describe latest strategies to combat antibiotic-resistant microbes.

PMID- 11343467
TI  - Thiazide use and reduced sodium intake for prevention of osteoporosis.

PMID- 11343468
TI  - Thiazide use and reduced sodium intake for prevention of osteoporosis.

PMID- 11343470
TI  - Industry support of researchers in universities and academic medical centers.

PMID- 11343471
TI  - Industry support of researchers in universities and academic medical centers.

PMID- 11343473
TI  - Bedside diagnostic tests for pulmonary embolism.

PMID- 11343474
TI  - Bedside diagnostic tests for pulmonary embolism.

PMID- 11343476
TI  - Prospects for research in diabetes mellitus.

PMID- 11343477
TI  - Cost-sharing for prescription drugs.

PMID- 11343479
TI  - Use of identification cards by underage youth to purchase tobacco.

PMID- 11343480
TI  - Long-term outcome of medical and surgical therapies for gastroesophageal reflux
      disease: follow-up of a randomized controlled trial.
AB  - CONTEXT: Severe gastroesophageal reflux disease (GERD) is a lifelong problem that
      can be complicated by peptic esophageal stricture and adenocarcinoma of the
      esophagus. OBJECTIVE: To determine the long-term outcome of medical and surgical
      therapies for GERD. DESIGN AND SETTING: Follow-up study conducted from October
      1997 through October 1999 of a prospective randomized trial of medical and
      surgical antireflux treatments in patients with complicated GERD. Mean (median)
      duration of follow-up was 10.6 years (7.3 years) for medical patients and 9.1
      years (6.3 years) for surgical patients. PARTICIPANTS: Two hundred thirty-nine
      (97%) of the original 247 study patients were found (79 were confirmed dead).
      Among the 160 survivors (157 men and 3 women; mean [SD] age, 67 [12] years), 129
      (91 in the medical treatment group and 38 in the surgical treatment group)
      participated in the follow-up. MAIN OUTCOME MEASURES: Use of antireflux
      medication, Gastroesophageal Reflux Disease Activity Index (GRACI) scores, grade
      of esophagitis, frequency of treatment of esophageal stricture, frequency of
      subsequent antireflux operations, 36-item Short Form health survey (SF-36)
      scores, satisfaction with antireflux therapy, survival, and incidence of
      esophageal adenocarcinoma, compared between the medical antireflux therapy group
      and the fundoplication surgery group. Information on cause of death was obtained
      from autopsy results, hospital records, and death certificates. RESULTS: Eighty
      three (92%) of 90 medical patients and 23 (62%) of 37 surgical patients reported
      that they used antireflux medications regularly (P<.001). During a 1-week period
      after discontinuation of medication, mean (SD) GRACI symptom scores were
      significantly lower in the surgical treatment group (82.6 [17.5] vs 96.7 [21.4]
      in the medical treatment group; P =.003). However, no significant differences
      between the groups were found in grade of esophagitis, frequency of treatment of
      esophageal stricture and subsequent antireflux operations, SF-36 standardized
      physical and mental component scale scores, and overall satisfaction with
      antireflux therapy. Survival during a period of 140 months was decreased
      significantly in the surgical vs the medical treatment group (relative risk of
      death in the medical group, 1.57; 95% confidence interval, 1.01-2.46; P =.047),
      largely because of excess deaths from heart disease. Patients with Barrett
      esophagus at baseline developed esophageal adenocarcinomas at an annual rate of
      0.4%, whereas these cancers developed in patients without Barrett esophagus at an
      annual rate of only 0.07%. There was no significant difference between groups in
      incidence of esophageal cancer. CONCLUSION: This study suggests that antireflux
      surgery should not be advised with the expectation that patients with GERD will
      no longer need to take antisecretory medications or that the procedure will
      prevent esophageal cancer among those with GERD and Barrett esophagus.

PMID- 11343481
TI  - Long-term effects of an early childhood intervention on educational achievement
      and juvenile arrest: A 15-year follow-up of low-income children in public
      schools.
AB  - CONTEXT: Most studies of the long-term effects of early childhood educational
      interventions are of demonstration programs rather than large-scale public
      programs. Previous studies of one of the oldest federally funded preschool
      programs have reported positive effects on school performance, but effects on
      educational attainment and crime are unknown. OBJECTIVE: To determine the long
      term effectiveness of a federal center-based preschool and school-based
      intervention program for urban low-income children. DESIGN, SETTING, AND
      PARTICIPANTS: Fifteen-year follow-up of a nonrandomized, matched-group cohort of
      1539 low-income, mostly black children born in 1980 and enrolled in alternative
      early childhood programs in 25 sites in Chicago, Ill. INTERVENTIONS: The Chicago
      Child-Parent Center (CPC) Program (n = 989 children) provides comprehensive
      education, family, and health services and includes half-day preschool at ages 3
      to 4 years, half- or full-day kindergarten, and school-age services in linked
      elementary schools at ages 6 to 9 years. The comparison group (n = 550) consisted
      of children who participated in alternative early childhood programs (full-day
      kindergarten): 374 in the preschool comparison group from 5 randomly selected
      schools plus 2 others that provided full-day kindergarten and additional
      instructional resources and 176 who attended full-day kindergartens in 6 CPCs
      without preschool participation. MAIN OUTCOME MEASURES: Rates of high school
      completion and school dropout by age 20 years, juvenile arrests for violent and
      nonviolent offenses, and grade retention and special education placement by age
      18 years. RESULTS: Relative to the preschool comparison group and adjusted for
      several covariates, children who participated in the preschool intervention for 1
      or 2 years had a higher rate of high school completion (49.7 % vs 38.5%; P =.01);
      more years of completed education (10.6 vs 10.2; P =.03); and lower rates of
      juvenile arrest (16.9% vs 25.1%; P =.003), violent arrests (9.0% vs 15.3%; P
      =.002), and school dropout (46.7% vs 55.0%; P =.047). Both preschool and school
      age participation were significantly associated with lower rates of grade
      retention and special education services. The effects of preschool participation
      on educational attainment were greater for boys than girls, especially in
      reducing school dropout rates (P =.03). Relative to less extensive participation,
      children with extended program participation from preschool through second or
      third grade also experienced lower rates of grade retention (21.9% vs 32.3%; P
      =.001) and special education (13.5% vs 20.7%; P =.004). CONCLUSIONS:
      Participation in an established early childhood intervention for low-income
      children was associated with better educational and social outcomes up to age 20
      years. These findings are among the strongest evidence that established programs
      administered through public schools can promote children's long-term success.

PMID- 11343482
TI  - Evaluation of contraceptive efficacy and cycle control of a transdermal
      contraceptive patch vs an oral contraceptive: a randomized controlled trial.
AB  - CONTEXT: Oral contraceptive (OC) pills are effective, but poor compliance
      increases rates of pregnancy during treatment. OBJECTIVE: To compare the
      contraceptive efficacy, cycle control, compliance, and safety of a transdermal
      contraceptive patch and an OC. DESIGN: Randomized, open-label, parallel-group
      trial conducted October 1997 to June 1999. SETTING: Forty-five clinics in the
      United States and Canada. PARTICIPANTS: A total of 1417 healthy adult women of
      child-bearing potential. INTERVENTIONS: Participants were randomly assigned to
      receive a transdermal contraceptive patch (n = 812) vs an OC (n = 605) for 6 or
      13 cycles. Patch treatment consisted of application of 3 consecutive 7-day
      patches followed by 1 patch-free week. MAIN OUTCOME MEASURES: Overall and method
      failure Pearl Indexes (number of pregnancies/100 person-years of use) and life
      table estimates of the probability of pregnancy were calculated. Cycle control,
      compliance, patch adhesion, and adverse events were also assessed. RESULTS:
      Overall and method-failure Pearl Indexes were numerically lower with the patch
      (1.24 and 0.99, respectively) vs the OC (2.18 and 1.25, respectively); this
      difference was not statistically significant (P =.57 and.80, respectively). The
      incidence of breakthrough bleeding and/or spotting was significantly higher only
      in the first 2 cycles in the patch group, but the incidence of breakthrough
      bleeding alone was comparable between treatments in all cycles. The mean
      proportion of participants' cycles with perfect compliance was 88.2% (811 total
      participants, 5141 total cycles) with the patch and 77.7% (605 total
      participants, 4134 total cycles) with the OC (P <.001). Only 1.8% (300/16 673) of
      patches completely detached. Both treatments were similarly well tolerated;
      however, application site reactions, breast discomfort, and dysmenorrhea were
      significantly more common in the patch group. CONCLUSION: The contraceptive patch
      is comparable to a combination OC in contraceptive efficacy and cycle control.
      Compliance was better with the weekly contraceptive patch than with the OC.

PMID- 11343483
TI  - Regular outpatient medical and drug abuse care and subsequent hospitalization of
      persons who use illicit drugs.
AB  - CONTEXT: Patients and the public could benefit from identification of factors
      that prevent drug users' heavy reliance on inpatient care; however, optimal
      health care delivery models for illicit drug users remain ill-defined. OBJECTIVE:
      To evaluate associations of outpatient medical and drug abuse care with drug
      users' subsequent hospitalization rates. DESIGN AND SETTING: Retrospective cohort
      study of data from longitudinally linked claims for all ambulatory
      physician/clinic services and drug abuse services covered by the New York State
      Medicaid program. SUBJECTS: A total of 11 556 human immunodeficiency virus (HIV)
      positive and 46 687 HIV-negative drug users. MAIN OUTCOME MEASURES:
      Hospitalization in federal fiscal year (FFY) 1997 compared by 4 patterns of care
      in FFY 1996: regular drug abuse care (>/=6 months in 1 program), regular medical
      care (>35% of care from 1 clinic, group practice, or individual physician), both,
      or neither. RESULTS: Hospitalization occurred in 55.6% of HIV-positive and 37.5%
      of HIV-negative drug users, with a mean of 27.5 and 24.5 inpatient days,
      respectively. In HIV-positive drug users, the adjusted odds ratio (AOR) for
      hospitalization was lowest among those with both regular medical and drug abuse
      care (AOR, 0.76; 95% confidence interval [CI], 0.67-0.85) followed by those with
      regular medical care alone (AOR, 0.82; 95% CI, 0.74-0.91) and regular drug abuse
      care alone (AOR, 0.85; 95% CI, 0.76-0.96) vs those with neither. In HIV-negative
      drug users, the AOR of hospitalization was lower for those with regular medical
      and drug abuse care (AOR, 0.73; 95% CI, 0.68-0.79), regular drug abuse care alone
      (AOR, 0.71; 95% CI, 0.66-0.76), and regular medical care (AOR, 0.91; 95% CI, 0.86
      0.95) vs those with neither. Both types of care showed favorable effects for all
      but drug abuse-related hospitalizations. CONCLUSION: Our data indicate that
      regular drug abuse care with regular medical care for drug users is associated
      with less subsequent hospitalization.

PMID- 11343484
TI  - Oregon physicians' attitudes about and experiences with end-of-life care since
      passage of the Oregon Death with Dignity Act.
AB  - CONTEXT: The Oregon Death with Dignity Act, passed by ballot measure in 1994 and
      enacted in October 1997, legalized physician-assisted suicide for competent,
      terminally ill Oregonians, but little is known about the effects of the act on
      clinical practice or physician perspective. OBJECTIVE: To examine Oregon
      physicians' attitudes toward and practices regarding care of dying patients since
      the passage of the Death with Dignity Act. DESIGN, SETTING, AND PARTICIPANTS: A
      self-administered questionnaire was mailed in February 1999 to Oregon physicians
      eligible to prescribe under the act. Of 3981 eligible physicians, 2641 (66%)
      returned the questionnaire by August 1999. MAIN OUTCOME MEASURES: Physicians'
      reports of their efforts to improve care for dying patients since 1994, their
      attitudes, concerns, and sources of information about participating in the Death
      with Dignity Act, and their conversations with patients regarding assisted
      suicide. RESULTS: A total of 791 respondents (30%) reported that they had
      increased referrals to hospice. Of the 2094 respondents who cared for terminally
      ill patients, 76% reported that they made efforts to improve their knowledge of
      the use of pain medications in the terminally ill. Nine hundred forty-nine
      responding physicians (36%) had been asked by a patient if they were potentially
      willing to prescribe a lethal medication. Seven percent of all survey
      participants reported that 1 or more patients became upset after learning the
      physician's position on assisted suicide, and 2% reported that 1 or more patients
      left their care after learning the physician's position on assisted suicide. Of
      the 73 physicians who were willing to write a lethal prescription and who had
      received a request from a patient, 20 (27%) were not confident they could
      determine when a patient had less than 6 months to live. CONCLUSION: Most Oregon
      physicians who care for terminally ill patients report that since 1994 they have
      made efforts to improve their ability to care for these patients and many have
      had conversations with patients about assisted suicide.

PMID- 11343485
TI  - Prevalence of diagnosed atrial fibrillation in adults: national implications for
      rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in
      Atrial Fibrillation (ATRIA) Study.
AB  - CONTEXT: Atrial fibrillation is the most common arrhythmia in elderly persons and
      a potent risk factor for stroke. However, recent prevalence and projected future
      numbers of persons with atrial fibrillation are not well described. OBJECTIVE: To
      estimate prevalence of atrial fibrillation and US national projections of the
      numbers of persons with atrial fibrillation through the year 2050. DESIGN,
      SETTING, AND PATIENTS: Cross-sectional study of adults aged 20 years or older who
      were enrolled in a large health maintenance organization in California and who
      had atrial fibrillation diagnosed between July 1, 1996, and December 31, 1997.
      MAIN OUTCOME MEASURES: Prevalence of atrial fibrillation in the study population
      of 1.89 million; projected number of persons in the United States with atrial
      fibrillation between 1995-2050. RESULTS: A total of 17 974 adults with diagnosed
      atrial fibrillation were identified during the study period; 45% were aged 75
      years or older. The prevalence of atrial fibrillation was 0.95% (95% confidence
      interval, 0.94%-0.96%). Atrial fibrillation was more common in men than in women
      (1.1% vs 0.8%; P<.001). Prevalence increased from 0.1% among adults younger than
      55 years to 9.0% in persons aged 80 years or older. Among persons aged 50 years
      or older, prevalence of atrial fibrillation was higher in whites than in blacks
      (2.2% vs 1.5%; P<.001). We estimate approximately 2.3 million US adults currently
      have atrial fibrillation. We project that this will increase to more than 5.6
      million (lower bound, 5.0; upper bound, 6.3) by the year 2050, with more than 50%
      of affected individuals aged 80 years or older. CONCLUSIONS: Our study confirms
      that atrial fibrillation is common among older adults and provides a contemporary
      basis for estimates of prevalence in the United States. The number of patients
      with atrial fibrillation is likely to increase 2.5-fold during the next 50 years,
      reflecting the growing proportion of elderly individuals. Coordinated efforts are
      needed to face the increasing challenge of optimal stroke prevention and rhythm
      management in patients with atrial fibrillation.

PMID- 11343486
TI  - Surgical therapy for reflux disease.

PMID- 11343487
TI  - Extended childhood intervention prepares children for school and beyond.

PMID- 11343493
TI  - Breastfeeding support benefits very low-birth-weight infants.

PMID- 11343494
TI  - Increased psychotropic medication use: are we improving mental health care or
      drugging our kids?

PMID- 11343495
TI  - Curtailing youth smoking.

PMID- 11343496
TI  - Randomized trial of breastfeeding support in very low-birth-weight infants.
AB  - OBJECTIVE: To determine if supplementary structured breastfeeding counseling
      (SSBC) for both parents compared with conventional hospital breastfeeding support
      (CHBS) improves the duration of breastfeeding in very low-birth-weight infants up
      to 1 year old. DESIGN: Randomized trial with longitudinal follow-up of infants at
      term, and ages 1, 3, 6, and 12 months (infant ages corrected for prematurity).
      SETTING: A tertiary-level neonatal intensive care unit (NICU) and geographically
      defined region in central-west Ontario, Canada. PARTICIPANTS: Parents of infants
      with a birth weight less than 1500 g, who planned to breastfeed. INTERVENTIONS:
      The SSBC consisted of viewing a video on breastfeeding for preterm infants;
      individual counseling by the research lactation consultant; weekly personal
      contact in the hospital; and frequent postdischarge contact through the infants'
      first year or until breastfeeding was discontinued. The CHBS group had standard
      breastfeeding support from regular staff members confined to the period of
      hospitalization in the NICU. MAIN OUTCOME MEASURE: Duration of breastfeeding.
      RESULTS: At study entry, there were no statistically significant differences in
      major demographic characteristics between groups. The mean duration of
      breastfeeding was 26.1 weeks (SD = 20.8; median, 17.4) in the SSBC group and 24.0
      weeks (SD = 20.5; median, 17.4) in the CHBS group (not statistically
      significant). CONCLUSIONS: Long-term breastfeeding counseling of parents of very
      low-birth-weight infants in this study did not demonstrate a significant
      difference in duration of breastfeeding. These results may be explained by the
      high motivation to breastfeed in both groups, a relatively advantaged population,
      and the availability of community breastfeeding resources, which may have
      diminished any significant differences that could have resulted from a
      breastfeeding intervention. The results of this study, compared with previous
      studies of very low-birth-weight infants, indicate a new trend to longer duration
      of breastfeeding in preterm infants.

PMID- 11343497
TI  - A physical activity screening measure for use with adolescents in primary care.
AB  - OBJECTIVE: To develop a reliable and valid physical activity screening measure
      for use with adolescents in primary care settings. STUDY DESIGN: We conducted 2
      studies to evaluate the test-retest reliability and concurrent validity of 6
      single-item and 3 composite measures of physical activity. Modifications were
      based on the findings of the 2 studies, and a best measure was evaluated in study
      3. Accelerometer data served as the criterion standard for tests of validity.
      RESULTS: In study 1 (N = 250; mean age, 15 years; 56% female; 36% white), reports
      on the composite measures were most reliable. In study 2 (N = 57; mean age, 14
      years; 65% female; 37% white), 6 of the 9 screening measures correlated
      significantly with accelerometer data. Subjects, however, had great difficulty
      reporting bouts of activity and distinguishing between intensity levels. Instead,
      we developed a single measure assessing accumulation of 60 minutes of moderate to
      vigorous physical activity. Evaluated in study 3 (N = 148; mean age, 12 years;
      65% female; 27% white), the measure was reliable (intraclass correlation, 0.77)
      and correlated significantly (r = 0.40, P<.001) with accelerometer data. Correct
      classification (63%), sensitivity (71%), and false-positive rates (40%) were
      reasonable. CONCLUSION: The "moderate to vigorous physical activity" screening
      measure is recommended for clinical practice with adolescents.

PMID- 11343498
TI  - Pediatric stimulant and selective serotonin reuptake inhibitor prescription
      trends: 1992 to 1998.
AB  - BACKGROUND: Presciption trends have key implications for costs, outcomes, and
      research, yet few data exist on pediatric selective serotonin reuptake inhibitor
      (SSRI) trends and associations with stimulant trends. OBJECTIVE: To describe
      prescription trends for stimulants, SSRIs, and combination prescriptions by age,
      sex, and race. METHODS: Retrospective population-based analysis of North Carolina
      Medicaid prescription claims files. PARTICIPANTS: North Carolina Medicaid
      recipients, 1992 through 1998, aged 1 to 19 years. The population ranged from 342
      333 children in 1992 to 581 088 in 1998. MAIN OUTCOME MEASURES: Annual number of
      prescriptions, patients filling a prescription claim, and prescription prevalence
      for stimulants and SSRIs. RESULTS: The number of children and adolescents who
      received stimulants increased from 6407 (24 584 claims) in 1992 to 27 951 (135
      057 claims) in 1998. The number of SSRI recipients increased from 510 children
      (1326 claims) in 1992 to 6984 children (25 392 claims) in 1998. Prescription
      prevalence in school-aged children 6 to 14 years increased from 4.4% to 9.5% for
      stimulants during the study period, and from 0.2% to 1.5% for SSRIs. In 1998,
      stimulant prescription prevalence was highest for white school-aged males (18.3%)
      vs black females (3.4%) and SSRI prescription prevalence was highest for white
      school-aged males (2.8%) vs black females (0.6%). Combination pharmacotherapy
      also increased during 1992 through 1998. CONCLUSIONS: Prevalence of stimulant and
      SSRI medications has increased during the 1990s, with prescription prevalence in
      North Carolina Medicaid youth higher than previously reported. Age, sex, and
      racial differences are apparent and call for further attention. Combination
      pharmacotherapy also has growing importance.

PMID- 11343499
TI  - Adolescent immunization practices: a national survey of US physicians.
AB  - BACKGROUND: Adolescent immunization rates remain low. Hence, a better
      understanding of the factors that influence adolescent immunization is needed.
      OBJECTIVE: To assess the adolescent immunization practices of US physicians.
      DESIGN AND SETTING: A 24-item survey mailed in 1997 to a national sample of 1480
      pediatricians and family physicians living in the United States, randomly
      selected from the American Medical Association's Master List of Physicians.
      PARTICIPANTS: Of 1110 physicians (75%) who responded, 761 met inclusion criteria.
      OUTCOME MEASURES: Immunization practices and policies, use of tracking and
      recall, opinions about school-based immunizations, and reasons for not providing
      particular immunizations to eligible adolescents. RESULTS: Seventy-nine percent
      of physicians reported using protocols for adolescent immunization, and 82%
      recommended hepatitis B immunization for all eligible adolescents. Those who did
      not routinely immunize adolescents often cited insufficient insurance coverage
      for immunizations. While 42% of physicians reported that they review the
      immunization status of adolescent patients at acute illness visits, only 24%
      immunized eligible adolescents during such visits. Twenty-one percent used
      immunization tracking and recall systems. Though 84% preferred that immunizations
      be administered at their practice, 71% of physicians considered schools, and 63%
      considered teen clinics to be acceptable alternative adolescent immunization
      sites. However, many had concerns about continuity of care for adolescents
      receiving immunizations in school. CONCLUSIONS: Most physicians supported
      adolescent immunization efforts. Barriers preventing adolescent immunization
      included financial barriers, record scattering, lack of tracking and recall, and
      missed opportunities. School-based immunization programs were acceptable to most
      physicians, despite concerns about continuity of care. Further research is needed
      to determine whether interventions that have successfully increased infant
      immunization rates are also effective for adolescents.

PMID- 11343500
TI  - State and federal compliance with the Synar Amendment: federal fiscal year 1998.
AB  - BACKGROUND: The Synar Amendment requires states and territories to enact a law
      prohibiting the sale of tobacco to minors and to enforce that law in a manner
      that could reasonably be expected to decrease the availability of tobacco to
      minors. OBJECTIVE: To determine if the Department of Health and Human Services
      (DHHS) and applicant states and territories are complying with the Synar
      Amendment. DATA SOURCES: Block grant applications from 59 states and territories
      describing activities during the federal fiscal year 1998. MEASURES: Whether
      applicants had enacted a tobacco sales law without loopholes, conducted
      enforcement inspections, penalized violators, and conducted a valid statewide
      survey with violation rates below the permissible threshold, and whether DHHS
      actions were consistent with the statutory requirements of the Synar Amendment.
      RESULTS: Three applicants had laws containing loopholes, 6 failed to conduct
      enforcement inspections, 7 failed to prosecute violators, 2 failed to conduct a
      valid survey, and 10 failed to demonstrate compliance with violation rate goals.
      Fifteen applicants failed 1 or more criteria and 8 were ultimately penalized by
      DHHS. No measurable progress in reducing violation rates was reported by 30
      states, with 16 reporting an increase during the previous year. Twenty-four
      applicants were granted delays. CONCLUSIONS: States that demonstrated remarkable
      progress were balanced by states with worsening performance; as a whole there was
      no significant national progress toward reducing the availability of tobacco to
      youths. This failure can be attributed to inadequate resources devoted to
      enforcement and reliance on merchant education in lieu of bona fide law
      enforcement.

PMID- 11343501
TI  - The relationship between lead exposure and homicide.
AB  - CONTEXT: Previous studies have suggested that excessive lead exposure is related
      to aggressive and violent behavior. OBJECTIVE: To evaluate the association
      between estimated air lead concentrations and homicide rates. DESIGN: Cross
      sectional ecological study. SETTING: All counties in the contiguous 48 states of
      the United States. EXPOSURE MEASURE: Estimated air lead concentrations and blood
      lead levels. MAIN OUTCOME MEASURE: The homicide rate in each county. RESULTS:
      Negative binomial regression was used to examine the relationship between air
      lead concentrations and the incidence of homicide across counties in the United
      States (N = 3111). After adjusting for sociologic confounding factors and 9
      measures of air pollution, the only indictor of air pollution found to be
      associated with homicide rates was air lead concentration. Across all counties,
      estimated air lead concentrations ranged from 0 to 0.17 microg/m(3). The adjusted
      results suggest that the difference between the highest and lowest level of
      estimated air lead is associated with a homicide incidence rate ratio of 4.12
      (95% confidence interval, 1.02-16.61). CONCLUSION: The results of this study
      support recent findings that there is an association between lead exposure and
      violent behavior.

PMID- 11343502
TI  - Home health nurse clinical assessment of neonatal jaundice: comparison of 3
      methods.
AB  - OBJECTIVE: To compare 3 methods of clinical assessment of jaundice in newborns by
      home health nurses. DESIGN: Prospective clinical trial. SETTING: Homes of
      newborns living within 10 miles of a 340-bed community hospital where they were
      delivered. PARTICIPANTS: Home health nurses and newborn patients (< or =2 weeks
      old). INTERVENTIONS: The nurses examined the newborns and documented whether they
      detected jaundice. In newborns thought to have jaundice, the nurses estimated
      bilirubin levels, documented the extent of caudal progression of the jaundice,
      and determined the Ingram (Cascade Health Care Products, Salem, Ore) icterometer
      readings from the newborns' noses. Total serum bilirubin tests were obtained from
      all newborns studied. OUTCOME MEASURES: Nurse assessment of the presence of
      jaundice and its caudal progression, nurse estimates of bilirubin levels,
      icterometer readings, and bilirubin levels. RESULTS: The nurses determined that
      82 (50%) of the 164 newborns had jaundice. Their estimates of bilirubin levels
      were most highly correlated with serum bilirubin levels (Pearson correlation,
      0.61). All 3 newborns with bilirubin levels greater than or equal to 291
      micromol/L (> or =17 mg/dL) were recognized by the nurses as having jaundice.
      These newborns had icterometer readings greater than or equal to 3.5 and had
      estimated bilirubin levels of greater than or equal to 274 micromol/L (> or =16
      mg/dL). CONCLUSIONS: The method of evaluation that each nurse was accustomed to
      using was the most accurate in determining the severity of newborn jaundice.
      These results suggest that postpartum home health nurses can effectively evaluate
      newborns for the presence and severity of jaundice.

PMID- 11343503
TI  - One hundred three consecutive patients with anorectal malformations and their
      associated anomalies.
AB  - OBJECTIVE: A long-term retrospective analysis of 103 infants with anorectal
      malformations (ARMs) was conducted to describe any associated congenital
      anomalies and surgical classifications. DESIGN: Retrospective medical record
      review. SETTING: This case series was conducted on all infants with ARMs born at,
      or referred to, any of 3 major medical centers in Wichita, Kan, for close to a 22
      year period. PATIENTS: The 103 infants in this study represent a consecutive
      sample of patients with ARMs. Patients were separated into 2 groups: isolated
      ARMs without associated anomalies (n = 30), and ARMs with associated anomalies (n
      = 73). The male-female ratio was 2:1. MAIN OUTCOME MEASURES: Patients with
      associated anomalies were further classified into groups of ARMs with minor
      anomalies; major anomalies; chromosomal abnormalities; and malformation
      syndromes, associations, or sequences. Only anomalies that occurred more than
      once were reported. Malformations were also classified according to major organ
      systems. RESULTS: The incidence of ARMs in our study was approximately 1 in 2500
      live births. Additional anomalies were found in 71% of infants with ARMs.
      Associated anomalies by major organ system included genitourinary anomalies
      (49%), musculoskeletal anomalies (43%), craniofacial anomalies (34%),
      cardiovascular anomalies (27%), gastrointestinal anomalies (18%), respiratory
      anomalies (13%), and central nervous system anomalies (12%). The most common
      chromosomal abnormalities were trisomies (8%), and ARMs were associated with
      VATER complex (vertebral defects, anal atresia, tracheoesophageal fistula with
      esophageal atresia, and radial and renal anomalies) in 11 cases (11%) and VACTERL
      (vertebral, anal, cardiac, tracheal, esophageal, renal, and limb anomalies) in 4
      cases (4%). CONCLUSIONS: Patients with ARMs have a high incidence of associated
      congenital anomalies. Evaluation of the most commonly affected organ systems in
      these infants is essential because it is these associated anomalies that account
      for most of the morbidity and mortality that is associated with this condition.

PMID- 11343504
TI  - Third-year medical student survey of office preceptorships during the pediatric
      clerkship.
AB  - OBJECTIVE: To assess medical students' interest in a career in pediatrics
      following their categorical pediatric clerkship. DESIGN: Satisfaction
      questionnaire to 704 third-year clerks in 5 university medical schools following
      the pediatric clerkship. METHODS: Analysis of the influence of the community
      office-based experience compared with the inpatient experience, and examination
      aspects of the office preceptorship most valued by the medical students. MAIN
      OUTCOME MEASURE: Satisfaction questionnaire addressing office-based experiences.
      RESULTS: Third-year pediatric clerks report that the private office setting
      provides a valuable learning experience, particularly when there is exposure to a
      wide spectrum of disease and when the preceptor had time to teach. Feelings about
      pediatrics as career choice rose during the clerkship from neutral to positive,
      and the frequency of strongly positive feelings rose from 9.2% to 28.6%. In
      deciding about pediatrics as a career, experiences with patients and residents in
      the inpatient setting still seem to count more than those experiences in the
      outpatient setting. CONCLUSION: Categorical pediatric clerkships provide learning
      environments that influence students positively toward pediatrics as a career
      choice. This choice is enhanced by encouraging community practitioners with
      students in their office to expose them to a wide variety of issues and devote
      time to teaching.

PMID- 11343505
TI  - Delivery of smoking prevention and cessation services to adolescents.
AB  - OBJECTIVES: To describe the delivery of smoking prevention and cessation
      screening and counseling practices to adolescents and to examine the effect of
      physician specialty, sex, practice characteristics, and familiarity with
      preventive care guidelines on the delivery of smoking cessation counseling
      services. METHODS: Cross-sectional self-reported survey of pediatricians and
      family physicians in 3 New York metropolitan statistical areas who had seen 1 or
      more adolescents for well care within the past 6 months. RESULTS: Of 564 eligible
      physicians, 371 (66%) responded. Physicians reported asking most adolescents
      about smoking (91%) but were less likely to ask about peer smoking use (41%) or
      smokeless tobacco use (32%). Similarly, they reported assessing motivation to
      quit for 81% of smokers, but less often helped set quit dates (34%) or scheduled
      follow-up visits (28%). Family physicians were more likely to provide more
      effective smoking cessation interactions than pediatricians (mean smoking
      counseling performance score, 61 vs. 53; P<.001). Family physicians were also
      more likely to be familiar with National Cancer Institute guidelines than
      pediatricians (48% vs. 27%; P<.001). Female physicians reported having spent more
      time with their last adolescent patient (mean, 26 vs 21 minutes; P<.001) and more
      often spent time alone with adolescent patients (85% vs. 76% of visits; P<.001)
      than did male physicians. In multivariate modeling, specialty, familiarity with
      National Cancer Institute guidelines, time spent, and confidentiality factors
      were associated with better smoking counseling performance. CONCLUSION:
      Familiarity with smoking cessation guidelines and physician's specialty and
      practice style with adolescents are associated with better delivery of tobacco
      cessation counseling to adolescents.

PMID- 11343506
TI  - Fever and stiff neck.

PMID- 11343507
TI  - Special feature: picture of the month. Infantile scurvy.

PMID- 11343508
TI  - Special feature: pathological case of the month. Pernicious anemia and gastric
      atrophy in an adolescent female with multiorgan problems.

PMID- 11343509
TI  - Special feature: pathological case of the month. Shwachman-Diamond syndrome: a
      syndrome of pancreatic insufficiency and bone marrow dysfunction.

PMID- 11343510
TI  - Special feature: radiological case of the month. Congenital syphilis presenting
      as osteomyelitis with normal radioisotope bone scan.

PMID- 11343511
TI  - Special feature: radiological case of the month. Pulmonary interstitial emphysema
      in a nonventilated preterm infant.

PMID- 11343512
TI  - The pediatric forum: is research on newborn circumcision ethical?

PMID- 11343514
TI  - The pediatric forum: cerebrospinal fluid protein concentration in full-term
      neonates.

PMID- 11343516
TI  - The pediatric forum: the necessity for statistical precision.

PMID- 11343521
TI  - Regional brain and ventricular volumes in Tourette syndrome.
AB  - BACKGROUND: The pathophysiology of Tourette syndrome (TS) is thought to involve
      disturbances in cortico-striato-thalamo-cortical circuitry. The morphological
      characteristics of the cortical and associated white matter portions of these
      circuits have not been previously examined in TS subjects. METHODS: High
      resolution anatomical magnetic resonance images were acquired in 155 TS and 131
      healthy children and adults. The cerebrums and ventricles were isolated and then
      parcellated into subregions using standard anatomical landmarks. RESULTS: For
      analyses that included both children and adults, TS subjects were found to have
      larger volumes in dorsal prefrontal regions, larger volumes in parieto-occipital
      regions, and smaller inferior occipital volumes. Significant inverse associations
      of cerebral volumes with age were seen in TS subjects that were not seen in
      healthy controls. Sex differences in the parieto-occipital regions of healthy
      subjects were diminished in the TS group. The age-related findings were most
      prominent in TS children, whereas the diminished sex differences were most
      prominent in TS adults. Group differences in regional ventricular volumes were
      less prominent than in the cerebrum. Regional cerebral volumes were significantly
      associated with the severity of tic symptoms in orbitofrontal, midtemporal, and
      parieto-occipital regions. CONCLUSIONS: Broadly distributed cortical systems are
      involved in the pathophysiology of TS. Developmental processes, sexual
      dimorphisms, and compensatory responses in these cortical regions may help to
      modulate the course and severity of tic symptoms.

PMID- 11343522
TI  - Neuroimaging of pediatric neuropsychiatric disorders: Is a picture really worth a
      thousand words?

PMID- 11343523
TI  - Cytokine-associated emotional and cognitive disturbances in humans.
AB  - BACKGROUND: Infectious, autoimmune, and neurodegenerative diseases are associated
      with profound psychological disturbances. Studies in animals clearly demonstrate
      that cytokines mediate illness-associated behavioral changes. However, the
      mechanisms underlying the respective psychological alterations in humans have not
      been established yet. Therefore, we investigated the effects of low-dose
      endotoxemia, a well-established and safe model of host-defense activation, on
      emotional, cognitive, immunological, and endocrine parameters. METHODS: In a
      double-blind, crossover study, 20 healthy male volunteers completed psychological
      questionnaires and neuropsychological tests 1, 3, and 9 hours after intravenous
      injection of Salmonella abortus equi endotoxin (0.8 ng/kg) or saline in 2
      experimental sessions. Blood samples were collected hourly, and rectal
      temperature and heart rate were monitored continuously. RESULTS: Endotoxin had no
      effects on physical sickness symptoms, blood pressure, or heart rate. Endotoxin
      caused a mild increase in rectal temperature (0.5 degrees C), and increased the
      circulating levels of tumor necrosis factor alpha (TNF-alpha), soluble TNF
      receptors, interleukin (IL)-6, IL-1 receptor antagonist, and cortisol. After
      endotoxin administration, the subjects showed a transient significant increase in
      the levels of anxiety (effect size [ES] = 0.55) and depressed mood (ES = 0.66).
      Verbal and nonverbal memory functions were significantly decreased (ES = 0.55 to
      0.64). Significant positive correlations were found between cytokine secretion
      and endotoxin-induced anxiety (r = 0.49 to r = 0.60), depressed mood (r = 0.40 to
      r = 0.75), and decreases in memory performance (r = 0.46 to r = 0.68).
      CONCLUSIONS: In humans, a mild stimulation of the primary host defense has
      negative effects on emotional and memory functions, which are probably caused by
      cytokine release. Hence, cytokines represent a novel target for
      neuropsychopharmacological research.

PMID- 11343524
TI  - Association of maladaptive parental behavior with psychiatric disorder among
      parents and their offspring.
AB  - BACKGROUND: A longitudinal study was conducted to investigate the role of
      maladaptive parental behavior in the association between parent and offspring
      psychiatric disorder. METHODS: Psychosocial and psychiatric interviews were
      administered to a representative community sample of 593 biological parents and
      their offspring from 2 counties in the state of New York in 1975, 1983, 1985 to
      1986, and 1991 to 1993. In 1975, the offspring were a mean age of 6 years.
      Maladaptive parental behavior was assessed in 1975, 1983, and 1985 to 1986.
      Parent and offspring psychiatric symptoms were assessed in 1983, 1985 to 1986,
      and 1991 to 1993. RESULTS: Maladaptive parental behavior substantially mediated a
      significant association between parental and offspring psychiatric symptoms.
      Parents with psychiatric disorders had higher levels of maladaptive behavior in
      the household than did parents without psychiatric disorders. Maladaptive
      parental behavior, in turn, was associated with increased offspring risk for
      psychiatric disorders during adolescence and early adulthood. Most of the youths
      that experienced high levels of maladaptive parental behavior during childhood
      had psychiatric disorders during adolescence or early adulthood, whether or not
      their parents had psychiatric disorders. In contrast, the offspring of parents
      with psychiatric disorders were not at increased risk for psychiatric disorders
      unless there was a history of maladaptive parental behavior. CONCLUSIONS:
      Maladaptive parental behavior is associated with increased risk for the
      development of psychiatric disorders among the offspring of parents with and
      without psychiatric disorders. Maladaptive parental behavior appears to be an
      important mediator of the association between parental and offspring psychiatric
      symptoms.

PMID- 11343525
TI  - Age-related changes in frontal and temporal lobe volumes in men: a magnetic
      resonance imaging study.
AB  - BACKGROUND: Imaging and postmortem studies provide converging evidence that,
      beginning in adolescence, gray matter volume declines linearly until old age,
      while cerebrospinal fluid volumes are stable in adulthood (age 20-50 years).
      Given the fixed volume of the cranium in adulthood, it is surprising that most
      studies observe no white matter volume expansion after approximately age 20
      years. We examined the effects of the aging process on the frontal and temporal
      lobes. METHODS: Seventy healthy adult men aged 19 to 76 years underwent magnetic
      resonance imaging. Coronal images focused on the frontal and temporal lobes were
      acquired using pulse sequences that maximized gray vs white matter contrast. The
      volumes of total frontal and temporal lobes as well as the gray and white matter
      subcomponents were evaluated. RESULTS: Age-related linear loss in gray matter
      volume in both frontal (r = -0.62, P<.001) and temporal (r = -0.48, P<.001) lobes
      was confirmed. However, the quadratic function best represented the relationship
      between age and white matter volume in the frontal (P<.001) and temporal (P<.001)
      lobes. Secondary analyses indicated that white matter volume increased until age
      44 years for the frontal lobes and age 47 years for the temporal lobes and then
      declined. CONCLUSIONS: The changes in white matter suggest that the adult brain
      is in a constant state of change roughly defined as periods of maturation
      continuing into the fifth decade of life followed by degeneration. Pathological
      states that interfere with such maturational processes could result in
      neurodevelopmental arrests in adulthood.

PMID- 11343526
TI  - Decreased somal size of deep layer 3 pyramidal neurons in the prefrontal cortex
      of subjects with schizophrenia.
AB  - BACKGROUND: Schizophrenia is associated with deficits in working memory, a
      cognitive function that depends on the connections of the prefrontal cortex (PFC)
      with the thalamus and other cortical regions. Pyramidal neurons in PFC deep layer
      3 play a central role in both thalamocortical and corticocortical circuitry.
      Given that somal size tends to be associated with both the dendritic and axonal
      architecture of a neuron, abnormalities in these circuits in schizophrenia may be
      associated with a change in the somal size of deep layer 3 pyramidal neurons.
      METHODS: We used design-based stereology to estimate the somal volume of
      pyramidal neurons in deep layer 3 of PFC area 9 in 28 subjects with
      schizophrenia, each of whom was matched to 1 normal comparison subject for sex,
      age, and postmortem interval. RESULTS: The geometric mean of the somal volume
      estimates in the subjects with schizophrenia was significantly (P =.02) decreased
      by 9.2%. This decrease was associated with a shift in the distribution of somal
      volumes toward smaller sizes. Neither antipsychotic medication treatment history
      nor duration of illness was associated with somal size. CONCLUSIONS: These
      findings independently replicate previous reports of decreased somal size in the
      PFC in schizophrenia. The reduction in size of deep layer 3 pyramidal neurons is
      consistent with abnormalities in thalamocortical and corticocortical circuitry,
      suggesting that disruption of these circuits may contribute to cognitive
      abnormalities in schizophrenia.

PMID- 11343527
TI  - Psychiatric disorders among tortured Bhutanese refugees in Nepal.
AB  - BACKGROUND: The impact of torture on the distribution of psychiatric disorders
      among refugees is unknown. METHODS: We surveyed a population-based sample of 418
      tortured and 392 nontortured Bhutanese refugees living in camps in Nepal. Trained
      interviewers assessed International Classification of Diseases, 10th Revision
      (ICD-10) disorders through structured diagnostic psychiatric interviews. RESULTS:
      Except for male sex, history of torture was not associated with demographics.
      Tortured refugees, compared with nontortured refugees, were more likely to report
      12-month ICD-10 posttraumatic stress disorder, persistent somatoform pain
      disorder, and dissociative (amnesia and conversion) disorders. In addition,
      tortured refugees were more likely to report lifetime posttraumatic stress
      disorder, persistent somatoform pain disorder, affective disorder, generalized
      anxiety disorder, and dissociative (amnesia and conversion) disorders. Tortured
      women, compared with tortured men, were more likely to report lifetime
      generalized anxiety disorder, persistent somatoform pain disorder, affective
      disorder, and dissociative (amnesia and conversion) disorders. CONCLUSIONS: Among
      Bhutanese refugees, the survivors had higher lifetime and 12-month rates of ICD
      10 psychiatric disorder. Men were more likely to report torture, but tortured
      women were more likely to report certain disorders. The results indicate the
      increased need for attention to the mental health of refugees, specifically
      posttraumatic stress disorder, persistent somatoform pain disorder, and
      dissociative (amnesia and conversion) disorders among those reporting torture.

PMID- 11343528
TI  - The toll of refugee status and the state of trauma research.

PMID- 11343529
TI  - Multicenter, double-blind comparison of sertraline and placebo in the treatment
      of posttraumatic stress disorder.
AB  - BACKGROUND: Posttraumatic stress disorder (PTSD) is a common illness associated
      with significant disability. Few large, placebo-controlled trials have been
      reported. METHODS: Outpatients with a DSM-III-R diagnosis of moderate-to-severe
      PTSD were randomized to 12 weeks of double-blind treatment with either sertraline
      (N = 100) in flexible daily doses in the range of 50 to 200 mg or placebo (N =
      108). Primary outcome measures consisted of the Clinician-Administered PTSD Scale
      (CAPS-2) total severity score, the patient-rated Impact of Event Scale (IES), and
      the Clinical Global Impression-Severity (CGI-S) and -Improvement (CGI-I) ratings.
      RESULTS: Mixed-effects analyses found significantly steeper improvement slopes
      for sertraline compared with placebo on the CAPS-2 (t = 2.96, P =.003), the IES
      (t = 2.26, P =.02), the CGI-I score (t = 3.62, P<.001), and the CGI-S score (t =
      4.40, P<.001). An intent-to-treat end-point analysis found a 60% responder rate
      for sertraline and a 38% responder rate for placebo (chi(2)(1) = 8.48, P =.004).
      Sertraline treatment was well tolerated, with a 9% discontinuation rate because
      of adverse events, compared with 5% for placebo. Adverse events that were
      significantly more common in subjects given sertraline compared with placebo
      consisted of insomnia (35% vs 22%), diarrhea (28% vs 11%), nausea (23% vs 11%),
      fatigue (13% vs 5%), and decreased appetite (12% vs 1%). CONCLUSION: The results
      of the current study suggest that sertraline is a safe, well-tolerated, and
      significantly effective treatment for PTSD.

PMID- 11343530
TI  - Supportive-expressive group therapy and distress in patients with metastatic
      breast cancer: a randomized clinical intervention trial.
AB  - BACKGROUND: Metastatic breast cancer carries with it considerable psychosocial
      morbidity. Studies have shown that some patients with metastatic breast cancer
      experience clinically significant anxiety and depression and traumatic stress
      symptoms. Supportive-expressive group psychotherapy was developed to help
      patients with cancer face and adjust to their existential concerns, express and
      manage disease-related emotions, increase social support, enhance relationships
      with family and physicians, and improve symptom control. METHODS: Of 125 women
      with metastatic breast cancer recruited into the study, 64 were randomized to the
      intervention and 61 to the control condition. Intervention women were offered 1
      year of weekly supportive-expressive group therapy and educational materials.
      Control women received educational materials only. Participants were assessed at
      baseline and every 4 months during the first year. Data at baseline and from at
      least 1 assessment were collected from 102 participants during this 12-month
      period, and these participants compose the study population. RESULTS: Primary
      analyses based on all available data indicated that participants in the treatment
      condition showed a significantly greater decline in traumatic stress symptoms on
      the Impact of Event Scale (effect size, 0.25) compared with the control
      condition, but there was no difference in Profile of Mood States total mood
      disturbance. However, when the final assessment occurring within a year of death
      was removed, a secondary analysis showed a significantly greater decline in total
      mood disturbance (effect size, 0.25) and traumatic stress symptoms (effect size,
      0.33) for the treatment condition compared with the control condition.
      CONCLUSION: Supportive-expressive therapy, with its emphasis on providing support
      and helping patients face and deal with their disease-related stress, can help
      reduce distress in patients with metastatic breast cancer.

PMID- 11343531
TI  - A 33-year follow-up of narcotics addicts.
AB  - BACKGROUND: This study examined longitudinal patterns of heroin use, other
      substance use, health, mental health, employment, criminal involvement, and
      mortality among heroin addicts. METHODS: The sample was composed of 581 male
      heroin addicts admitted to the California Civil Addict Program (CAP) during the
      years 1962 through 1964; CAP was a compulsory drug treatment program for heroin
      dependent criminal offenders. This 33-year follow-up study updates information
      previously obtained from admission records and 2 face-to-face interviews
      conducted in 1974-1975 and 1985-1986; in 1996-1997, at the latest follow-up, 284
      were dead and 242 were interviewed. RESULTS: In 1996-1997, the mean age of the
      242 interviewed subjects was 57.4 years. Age, disability, years since first
      heroin use, and heavy alcohol use were significant correlates of mortality. Of
      the 242 interviewed subjects, 20.7% tested positive for heroin (with additional
      9.5% urine refusal and 14.0% incarceration, for whom urinalyses were
      unavailable), 66.9% reported tobacco use, 22.1% were daily alcohol drinkers, and
      many reported illicit drug use (eg, past-year heroin use was 40.5%; marijuana,
      35.5%; cocaine, 19.4%; crack, 10.3%; amphetamine, 11.6%). The group also reported
      high rates of health problems, mental health problems, and criminal justice
      system involvement. Long-term heroin abstinence was associated with less
      criminality, morbidity, psychological distress, and higher employment.
      CONCLUSIONS: While the number of deaths increased steadily over time, heroin use
      patterns were remarkably stable for the group as a whole. For some, heroin
      addiction has been a lifelong condition associated with severe health and social
      consequences.

PMID- 11343532
TI  - Leptin as a possible modulator of craving for alcohol.

PMID- 11343533
TI  - Admixture analysis of age at onset in bipolar I affective disorder.

PMID- 11343534
TI  - Fish consumption, depression, and suicidality in a general population.

PMID- 11343536
TI  - Low salivary cortisol levels and aggressive behavior.

PMID- 11343538
TI  - A lofty mountain to scale: a tale of perseverance.

PMID- 11343539
TI  - Spiral computed tomography for the diagnosis of pulmonary embolism in critically
      ill surgical patients: a comparison with pulmonary angiography.
AB  - HYPOTHESIS: Spiral computed tomographic pulmonary angiography (CTPA) is sensitive
      and specific in diagnosing pulmonary embolism (PE) in critically ill surgical
      patients. DESIGN: Prospective study comparing CTPA with the criterion standard,
      pulmonary angiography (PA). SETTING: Surgical intensive care unit of an academic
      hospital. PATIENTS: Twenty-two critically ill surgical patients with clinical
      suspicion of PE. The CTPAs and PAs were independently read by 4 radiologists (2
      for each test) blinded to each other's interpretation. Clinical suspicion was
      classified as high, intermediate, or low according to predetermined criteria. All
      but 2 patients had marked pulmonary parenchymal disease at the time of the event
      that triggered evaluation for PE. INTERVENTIONS: Computed tomographic pulmonary
      angiography and PA in 22 patients, venous duplex scan in 19. RESULTS: Eleven
      patients (50%) had evidence of PE on PA, 5 in central and 6 in peripheral
      pulmonary arteries. The sensitivity and specificity of CTPA was, respectively,
      45% and 82% for all PEs, 60% and 100% for central PEs, and 33% and 82% for
      peripheral PEs. Duplex scanning was 40% sensitive and 100% specific in diagnosing
      PE. The independent reviewers disagreed only in 14% of CTPA and 14% of PA
      interpretations. There were no differences in risk factors or clinical
      characteristics between patients with and without PE. The level of clinical
      suspicion was identical in the 2 groups. CONCLUSIONS: Pulmonary angiography
      remains the gold standard for the diagnosis of PE in critically ill surgical
      patients. Computed tomographic pulmonary angiography needs further evaluation in
      this population.

PMID- 11343541
TI  - Timing of urgent thoracotomy for hemorrhage after trauma: a multicenter study.
AB  - HYPOTHESIS: It is possible to quantify an amount of thoracic hemorrhage, after
      blunt and penetrating injury, at which delay of thoracotomy is associated with
      increased mortality. DESIGN: A retrospective case series. SETTING: Five urban
      trauma centers. STUDY SELECTION: Patients undergoing urgent thoracotomy (within
      48 hours of injury) for hemorrhage (excluding emergency department thoracotomy).
      DATA EXTRACTION: Respective registries identified patients who underwent urgent
      thoracotomy. Injury characteristics, initial and subsequent chest tube outputs,
      time before thoracotomy, and outcomes were evaluated. MAIN OUTCOME MEASURE:
      Death. RESULTS: One hundred fifty-seven patients (36 with blunt and 121 with
      penetrating injuries) underwent urgent thoracotomy for hemorrhage between January
      1, 1995, and December 31, 1998. Mortality correlated with mean (+/- SD) Injury
      Severity Score (38 +/- 19 vs 22 +/- 12.6 for survivors; P<.01) and mechanism (24
      [67%] for blunt vs 21 [17%] for penetrating injuries; P<.01). Mortality increased
      as total chest blood loss increased, with the risk for death at blood loss of
      1500 mL being 3 times greater than at 500 mL. Blunt-injured patients waited a
      significantly longer time to thoracotomy than penetrating-injured patients (4.4
      +/- 9.0 h vs 1.6 +/- 3.0 h; P =.02) and also had a greater total chest tube
      output before thoracotomy (2220 +/- 1235 mL vs 1438 +/- 747 mL; P =.001).
      CONCLUSIONS: The risk for death increases linearly with total chest hemorrhage
      after thoracic injury. Thoracotomy is indicated when total chest tube output
      exceeds 1500 mL within 24 hours, regardless of injury mechanism.

PMID- 11343542
TI  - The long-term benefit of surgery on health-related quality of life in patients
      with inflammatory bowel disease.
AB  - HYPOTHESES: Health-related quality of life (HRQL) has been shown to improve
      dramatically shortly after surgery in patients with inflammatory bowel disease
      (IBD). Our hypotheses were that (1) improved HRQL would be maintained long term
      in patients after surgery for ulcerative colitis and (2) the improved HRQL in
      patients with Crohn disease would decline with long-term follow-up. DESIGN:
      Consecutive series of patients undergoing surgery for IBD between June 1994 and
      January 2000 prospectively investigated as a cohort outcomes study. PATIENTS:
      Data were obtained in 139 patients. The diagnoses were Crohn disease (n = 56) and
      ulcerative colitis (n = 83). INTERVENTION: Patients with Crohn disease underwent
      resections with or without stricturoplasties; all but 5 patients with ulcerative
      colitis underwent ileal pouch-anal anastomoses. MAIN OUTCOME MEASURE: Health
      status was measured using the Health Status Questionnaire (HSQ) preoperatively
      and then every 3 months postoperatively. RESULTS: Preoperative HSQ scores were
      very low in all 8 scales of the HSQ. Postoperatively, HRQL measures improved
      significantly (P<.05) both in patients with Crohn disease and ulcerative colitis,
      with scores equal to or better than published scores in the general population.
      In patients with Crohn disease, the scores improved significantly after surgical
      resection and steadily increased despite disease recurrence and reoperations. The
      HRQL at last follow-up was equivalent to the general population. The improvements
      were statistically significant in patients followed up for more than 1 year in 7
      of 8 scales of the HSQ. CONCLUSIONS: These results confirm that HRQL is poor in
      patients with IBD referred for possible operation. Surgical resection resulted in
      significant improvement in HRQL. More important, the results were durable. With
      follow-up up to 6 years, the HRQL in this cohort was equal to or better than
      norms for the general population both in patients with ulcerative colitis and
      with Crohn disease. We believe these data justify aggressive surgical
      intervention in many patients with IBD and support the prospective study of HRQL
      by surgeons treating patients with chronic diseases.

PMID- 11343543
TI  - Underlying liver disease, not tumor factors, predicts long-term survival after
      resection of hepatocellular carcinoma.
AB  - HYPOTHESIS: A subset of patients can be identified who will survive without
      recurrence beyond 5 years after hepatic resection for hepatocellular carcinoma
      (HCC). DESIGN: A retrospective review of a multi-institutional database of 591
      patients who had undergone hepatic resection for HCC and on-site reviews of
      clinical records and pathology slides. SETTING: All patients had been treated in
      academic referral centers within university-based hospitals. PATIENTS: We
      identified 145 patients who had survived for 5 years or longer after hepatic
      resection for HCC. MAIN OUTCOME MEASURES: Clinical and pathologic factors, as
      well as scoring of hepatitis and fibrosis in the surrounding liver parenchyma,
      were assessed for possible association with survival beyond 5 years and cause of
      death among the 145 five-year survivors. RESULTS: Median additional survival
      duration longer than 5 years was 4.1 years. Women had significantly longer median
      additional survival durations than did men (81 months vs 38 months, respectively,
      after the 5-year mark) (P =.008). Surgical margins, type of resection, an
      elevated preoperative alpha-fetoprotein level, and the presence of multiple
      tumors or microscopic vascular invasion had no bearing on survival longer than 5
      years. However, patients who survived for 5 years who also had normal underlying
      liver or minimal fibrosis (score, 0-2) at surgery had significantly longer
      additional survival than did patients with moderate fibrosis (score, 3-4) or
      severe fibrosis/cirrhosis (score, 5-6) (P<.001). CONCLUSIONS: Death caused by HCC
      is rare beyond 5 years after resection of HCC in the absence of fibrosis or
      cirrhosis. The data suggest that chronic liver disease acts as a field of
      cancerization contributing to new HCC. These patients may benefit from therapies
      directed at the underlying liver disease.

PMID- 11343544
TI  - Use of intraoperative parathyroid hormone measurement does not improve success of
      bilateral neck exploration for hyperparathyroidism.
AB  - HYPOTHESIS: Use of intraoperative measurement of intact parathyroid hormone
      (iPTH) to confirm complete excision of hyperfunctioning parathyroid tissue does
      not improve overall operative success rates. DESIGN: Case series of patients
      undergoing parathyroidectomy with or without intraoperative iPTH measurement.
      SETTING: University teaching hospital. PATIENTS AND INTERVENTIONS: Fifty patients
      undergoing parathyroidectomy before our institution of intraoperative iPTH
      sampling in March 1999 (group 1) were compared with 50 patients undergoing
      parathyroidectomy after this technique was adopted (group 2). Overall, 100
      patients underwent operation between December 1996 and May 2000. Serum calcium
      and iPTH levels were measured at 1- and 3-month intervals. Intraoperative frozen
      sections and operative times were also analyzed. RESULTS: Mean preoperative
      calcium levels were 2.85 and 2.82 mmol/L (11.4 and 11.3 mg/dL) in groups 1 and 2,
      respectively. One-month postoperative calcium values were identical in both
      groups at 2.35 mmol/L (9.4 mg/dL) (group 1 SD = 0.18 [0.74], group 2 SD = 0.20
      [0.82]). At 1 month, all but 1 patient in group 1 had normalized calcium values
      (2% failure rate), while 3 patients in group 2 (6%) remained hypercalcemic. All 3
      patients in group 2 had intraoperative iPTH levels that returned to normal. There
      was a significant difference in the number of intraoperative frozen sections
      between groups, with a mean (SD) of 3.4 (1.7) in group 1 and 2.0 (1.6) in group 2
      (P<.01). There was no significant difference in operative times between groups.
      CONCLUSIONS: Use of intraoperative iPTH sampling did not significantly affect the
      overall success of parathyroidectomy, as determined by postoperative
      normocalcemia. There was, however, a significant decrease in the number of frozen
      sections sent at operation.

PMID- 11343545
TI  - Adrenocortical carcinoma: surgical progress or status quo?
AB  - HYPOTHESIS: Outcome of patients with adrenocortical carcinoma (ACC) has improved
      with the advent of more widely available and higher quality imaging. Operative
      management strategies and use of adjuvant therapy have not changed. DESIGN:
      Retrospective review of patient histories, imaging studies, operative data,
      adjuvant therapy, and outcomes at a single institution. Follow-up was complete
      for a mean of 53 months. Data was compared with prior institutional experience.
      SETTING: Tertiary care referral center. PATIENTS: All patients undergoing
      operative management for ACC during the period from 1980 to 1996. MAIN OUTCOME
      MEASURES: Determinants of recurrence, survival, and the effect of adjuvant
      therapy on overall outcome. RESULTS: Fifty-eight patients (30 men, 28 women) with
      a mean age of 53 years underwent primary operative management for ACC. Functional
      tumors were identified in 27 patients (47%). Mean tumor size was 12.5 cm. Stage
      according to the TNM staging system (AJCC Cancer Staging Manual) at presentation
      was I (n = 0), II (n = 30), III (n = 7), and IV (n = 21). Surgical management
      included curative resection in 41 (71%), noncurative resection in 14 (24%), and
      open biopsy in 3 (5%). Perioperative mortality was 5%. Recurrence occurred in 30
      patients (73%) with a median time to recurrence of 17 months. Five-year survival
      by the Kaplan-Meier method was 37%. Prognostic factors (P<.05) included
      functional status, stage, and chemotherapy in stage III/IV patients. When
      compared with our prior institutional experience (1960-1980), current patients
      were more likely to present with stages I to II (52% vs. 34%), have curative
      resections (71% vs. 50%), and have improved 5-year survival (37% vs. 16%).
      CONCLUSIONS: (1) Surgical resection remains the principal treatment for stage I
      to III disease. (2) Adjuvant therapy may improve survival in patients with stage
      III or IV disease. (3) Current patients were more likely to present at an earlier
      stage, undergo curative resections, and have improved 5-year survival than
      institutional historical comparisons.

PMID- 11343546
TI  - Operative management of chronic pancreatitis in children.
AB  - HYPOTHESIS: Chronic pancreatitis in childhood is a rare but potentially
      debilitating disorder, and failure of conservative therapy with chronic pain
      medication use is common. We hypothesize that aggressive surgical therapy may
      hold promise for long-term remission. DESIGN: Retrospective analysis of data
      collected prospectively for 12 years. SETTING: Tertiary care children's hospital.
      PATIENTS: Eighteen children (aged 3-13 years, 11 girls) underwent surgical
      treatment of chronic pancreatitis after 1 to 6 years of various medical therapies
      (parenteral nutrition, somatostatin, or pain medication). These patients required
      a mean +/- SD 6 +/- 0 hospitalizations before operation. Pancreatitis was
      familial in 9 patients, idiopathic in 5, and secondary to trauma and medication
      use in 2 each. Preoperative endoscopic retrograde cholangiopancreatography showed
      pancreatic duct dilatation in 7, strictures in 5, ductal stones in 4, and normal
      findings in 2. The operative therapy consisted of longitudinal
      pancreaticojejunostomy in 2 children (both children failed pancreaticojejunostomy
      but improved after undergoing pancreatectomy) and distal pancreatectomy with Roux
      en-Y pancreaticojejunostomy in 16 children. OUTCOME MEASURES: Survival, need for
      rehospitalization or reoperation, and chronic pain medication requirements.
      RESULTS: All patients survived. Follow-up ranged from 1 to 15 years. Thirteen
      (72%) of 18 patients have required no further hospitalizations or medications.
      Two patients required a second operation to convert their longitudinal
      pancreaticojejunostomy to distal pancreatectomy, and 3 patients have required 2
      to 5 additional hospitalizations for recurrent pancreatitis. Endoscopic
      retrograde cholangiopancreatography on 5 patients 2 to 4 years postoperatively
      showed patent distal pancreaticojejunostomy. CONCLUSIONS: This series suggests
      that distal pancreatectomy and pancreaticojejunostomy are effective treatments
      for this difficult group of patients, while longitudinal pancreaticojejunostomy
      was ineffective. Long-term relief of pain and reduced need for rehospitalization
      are the usual results after this procedure.

PMID- 11343547
TI  - Computed tomography and ultrasonography do not improve and may delay the
      diagnosis and treatment of acute appendicitis.
AB  - HYPOTHESIS: Computed tomography (CT) and ultrasonography (US) do not improve the
      overall diagnostic accuracy for acute appendicitis. DESIGN: Retrospective review.
      SETTING: University tertiary care center. PATIENTS: Seven hundred sixty-six
      consecutive patients undergoing appendectomy for suspected appendicitis from
      January 1, 1995, to December 31, 1999. MAIN OUTCOME MEASURES: Epidemiology of
      acute appendicitis and the roles of clinical assessment, CT, US, and laparoscopy.
      RESULTS: The negative appendectomy rate was 15.7%, and the incidence of
      perforated appendicitis was 14.6%. A history of migratory pain had the highest
      positive predictive value (91%), followed by leukocytosis greater than 12 x
      10(9)/L (90.1%), CT (83.8%), and US (81.3%). The false-negative rates were 60%
      for CT and 76.1% for US. Emergency department evaluation took a mean +/- SD of
      5.2 +/- 5.4 hours and was prolonged by US or CT (6.4 +/- 7.4 h and 7.8 +/- 10.8
      h, respectively). The duration of emergency department evaluation did not affect
      the perforation rate, but patients with postoperative complications had longer
      evaluations (mean +/- SD, 8.0 +/- 12.7 h) than did those without (4.8 +/- 3.3 h)
      (P =.04). Morbidity was 9.1%, 6.4% for nonperforated cases and 19.8% for
      perforated cases. Seventy-six patients had laparoscopic appendectomy, with a
      negative appendectomy rate of 42.1%, compared with 15.4% for open appendectomy
      (P<.001). Laparoscopy, however, had minimal morbidity (1.3%) and correctly
      identified the abnormality in 91.6% of patients who had a normal-appearing
      appendix. CONCLUSIONS: Migratory pain, physical examination, and initial
      leukocytosis remain reliable and accurate in diagnosing acute appendicitis.
      Neither CT nor US improves the diagnostic accuracy or the negative appendectomy
      rate; in fact, they may delay surgical consultation and appendectomy. In atypical
      cases, one should consider the selective use of diagnostic laparoscopy instead.

PMID- 11343548
TI  - Predicting the status of the nonsentinel axillary nodes: a multicenter study.
AB  - BACKGROUND: Sentinel lymph node (SLN) biopsy is a minimally invasive procedure
      that provides accurate nodal staging information. The need for completion
      axillary dissection after finding a positive SLN for breast cancer has been
      questioned. HYPOTHESIS: The presence of nonsentinel node (NSN) metastases in the
      axillary dissection specimen correlates with tumor size, the number of SLNs
      removed, and the number of positive SLNs. DESIGN: Prospective, multi
      institutional study. PARTICIPANTS AND METHODS: The University of Louisville
      Breast Cancer Sentinel Lymph Node Study is a nationwide study involving 148
      surgeons. All patients underwent SLN biopsy, followed by level I/II axillary
      dissection. All SLNs were evaluated histologically at a minimum of 2-mm
      intervals. Immunohistochemical analysis using antibodies for cytokeratin was
      performed at the discretion of each participating institution. All NSNs were
      evaluated by routine histologic examination. RESULTS: An SLN was identified in
      1268 (90%) of 1415 patients. Increasing tumor size was significantly correlated
      with increasing likelihood of positive NSNs: T1a, 14%; T1b, 22%; T1c, 30%; T2,
      45%; and T3, 57% (P =.002, chi(2) test). The presence of positive NSNs was not
      significantly associated with the number of SLNs removed. Patients with more than
      1 positive SLN were more likely to have positive NSNs than those with only 1
      positive SLN (50% vs 32%; P<.001, chi(2) test). Increasing tumor size and the
      presence of multiple positive SLNs were also associated with the presence 4 or
      more positive axillary nodes. Multivariate analysis confirmed that tumor size and
      the number of positive SLNs were independent factors predicting the presence of
      positive NSNs. CONCLUSIONS: The likelihood of positive NSNs correlates with
      increasing tumor size and the presence of multiple positive SLNs. However, even
      patients with small primary tumors have a substantial risk of residual axillary
      nodal disease after SLN biopsy. These data will be helpful in counseling patients
      regarding the need for completion axillary dissection after a positive SLN is
      identified.

PMID- 11343549
TI  - Is any method of vascular control superior in hepatic resection of metastatic
      cancers? Longmire clamping, pringle maneuver, and total vascular isolation.
AB  - HYPOTHESIS: Although control of the hepatic vascular pedicle is commonly used
      during hepatic resection, the optimal method of vascular control continues to be
      debated. The utility of total or selective vascular isolation, pedicle inflow
      occlusion, or the absence of vascular isolation during minor and major
      hepatectomy needs to be examined. DESIGN: Retrospective review of hepatic
      resections performed for either isolated colorectal or noncolorectal hepatic
      metastases. SETTING: The University of Chicago Hospitals, Chicago, Ill, a
      tertiary-care referral center. PATIENTS: One hundred forty-one patients who
      underwent hepatic resection for isolated metastatic liver disease were identified
      through The University of Chicago Hospitals Tumor Registry. MAIN OUTCOME
      MEASURES: Intraoperative parameters, perioperative morbidity and mortality, and
      tumor recurrence. RESULTS: Four groups were compared with alternative methods of
      vascular management, including total vascular isolation, Longmire clamping,
      Pringle maneuver, or no vascular control. Tumor number and size were not
      significantly different between groups. Blood loss and transfusion requirements
      tended to be higher in the total vascular isolation group and were significantly
      higher compared with the Pringle group (P =.06) and the no vascular control group
      (P =.04), but this also correlated with a higher incidence of complexity of
      surgical resection. The highest incidence of postoperative complications occurred
      in the total vascular isolation group (P<.05). With similar permanent pathologic
      margins, the rates of intrahepatic recurrence were similar among all groups, with
      the no vascular control group having the lowest recurrence rate. CONCLUSIONS: All
      methods of vascular control appeared equivalent with respect to limiting blood
      loss and transfusion requirements while providing adequate surgical margins. The
      highest rates of blood requirements and complications were noted in the total
      vascular isolation group, which corresponded to the highest incidence of complex
      resections. The Longmire clamp group incurred the lowest incidence of
      complications and resulted in identical surgical margins. The application of
      vascular control is beneficial to surgeons during hepatic resection, but the
      method of control should be selected based on the location and complexity of
      resection required and preference of the individual surgeon.

PMID- 11343551
TI  - Congenital duodenal anomalies in the adult.
AB  - BACKGROUND: Duodenal anomalies are defects in embryologic development and usually
      present as gastric outlet obstruction in infancy or early childhood.
      Occasionally, they remain asymptomatic until adulthood and, because they are
      unusual, may not be diagnosed. HYPOTHESIS: Based on current experience and review
      of the literature, recognition of diagnosis and the preferred methods of
      treatment of duodenal anomalies can be recommended. DESIGN: Retrospective study
      of congenital duodenal anomalies in adults. SETTING: Tertiary care university
      medical center. PATIENTS: Twenty-nine patients were observed and treated between
      1983 and 1999 (19 women and 10 men; mean +/- SD age, 52 +/- 16 years). Twenty
      patients had duodenal webs, 7 had annular pancreata, and 2 had both. Nausea,
      vomiting, abdominal pain, and weight loss were predominant symptoms in all
      groups. Peptic ulceration occurred in 13 of 20 patients with webs but in none of
      those with annular pancreata or combined anomaly. MAIN OUTCOME MEASURES: Surgical
      outcomes including postoperative complications, deaths, and resolution of
      preoperative symptoms. RESULTS: The treatment for patients with duodenal webs was
      transduodenal web excision and duodenoplasty in 19 of 22. Patients with annular
      pancreata were treated by transection of the annulus and duodenoplasty (n = 4)
      and proximal duodenal bypass (n = 3). There were no operative deaths, but 44% of
      patients had some complications. No pancreatic fistulas occurred in patients who
      had division of an annular pancreas. Outcome was considered excellent or good in
      17 of 20 patients with duodenal webs, 4 of 7 with annular pancreata, and 2 of 2
      with the combined anomaly. CONCLUSIONS: Duodenal anomalies are rare in adults.
      Duodenal webs are best managed by transduodenal excision and duodenoplasty.
      Annular pancreas is generally best treated by duodenal bypass to the distal
      duodenum or the jejunum. Annulus division can be carried out if the annulus is
      extramural, without duodenal stenosis, and if access to the pancreaticobiliary
      sphincters is necessary.

PMID- 11343552
TI  - The health care crisis: impact on surgery in the community hospital setting.
AB  - Hospitals and health systems across the United States are in crisis. The causes
      of this crisis are multiple, and they reflect the interplay among reduced
      operating margins, workforce issues, the technology explosion, consumerism, and
      leadership. They affect hospitals of every type and location. In aggregate, they
      profoundly influence our trifold mission of patient care, education, and
      research. Departments of surgery have a disproportionate effect on hospital
      financial viability, and therefore, surgical leaders must work with other
      clinical and administrative leaders to manage these issues. This article is a
      personal view of how this crisis has affected our community-based academic
      medical center, William Beaumont Hospital, Royal Oak, Mich.

PMID- 11343553
TI  - Pancreatic infection in severe pancreatitis: the role of fungus and
      multiresistant organisms.
AB  - HYPOTHESIS: Recent controlled clinical studies suggest a positive effect of early
      antibiotic treatment on late morbidity and mortality in severe acute
      pancreatitis. However, widespread use of antibiotics may lead to an increased
      number of fungal infections and multiresistant bacteria, thereby worsening the
      outcome of the disease. DESIGN: Single-center prospective study. SETTING:
      University hospital, gastrointestinal surgical service. PATIENTS: One hundred
      three patients with necrotizing pancreatitis seen consecutively in our service.
      INTERVENTIONS: In addition to standard treatment, patients with proven
      necrotizing pancreatitis received a prophylactic intravenous antibiotic
      treatment. Pancreatic infection was regarded as an indication for surgery. MAIN
      OUTCOME MEASURES: Pancreatic infection, microbiological findings, drug
      resistance, fungal infections. RESULTS: Thirty-three patients (32%) had infected
      necrosis. Gram-negative organisms were isolated from 19 patients (58%), Gram
      positive organisms were isolated from 18 patients (55%), fungal organisms were
      isolated from 8 patients (24%), and multiresistant organisms were isolated from 3
      patients (9%). In 7 patients (21%), the organisms cultured from the pancreatic
      tissue were resistant to the antibiotics given in for prophylaxis. Infection with
      multiresistant organisms or organisms resistant to the antibiotic used for
      prophylaxis, but not with fungal infection or Gram-positive or Gram-negative
      infection, was correlated with a negative outcome. CONCLUSIONS: Fungal infection
      under adequate treatment is not associated with a negative outcome. The
      occurrence of multiresistant organisms seems to be a rare finding (3 of 103
      patients). Antibiotic prophylaxis is effective in preventing infection in
      necrotizing pancreatitis, but optimal choice and duration of administration of
      the antibiotic agent(s) need to be carefully determined to avoid the sequelae of
      multiresistant organisms.

PMID- 11343554
TI  - Special feature: image of the month. Gastric Stromal tumor (leiomyoma vs.
      leiomyosarcoma).

PMID- 11343555
TI  - Elucidation of active anticancer agents in naturally occurring substances.

PMID- 11343556
TI  - Surgical reminiscence: Zora: a potluck case.

PMID- 11343557
TI  - Moments in surgical history: the doctors Mayo.

PMID- 11343558
TI  - Cerebral protection during surgery for aortic arch aneurysms.
AB  - Surgical repair of aneurysms or dissections involving the transverse aortic arch
      and the distal aortic arch carries a considerable risk of cerebral complications.
      Currently, deep hypothermic circulatory arrest (DHCA), moderate hypothermic
      circulatory arrest or DHCA with selective cerebral perfusion (SCP) and DHCA with
      retrograde cerebral perfusion (RCP) are used as means to protect the central
      nervous system. DHCA alone is simple, but the safe time of DHCA is limited. RCP
      is an alternative technique for cerebral protection that can prolong the safe
      time of DHCA. SCP offers virtually unlimited time in isolating cerebral
      circulation. With the improvement of cardiopulmonary bypass (CPB) materials and
      myocardial preservation, DHCA with SCP is our current preference of an adjunct
      for cerebral protection, although possible increment of mortality and morbidity
      associated with a prolonged DHCA and CPB remains to be overcome.

PMID- 11343559
TI  - Hydatid cysts of the lung in childhood: is capitonnage advantageous?
AB  - In the treatment of thoracal hydatid cysts, there is not an agreement whether the
      cyst cavity to be capitonnaged or not. In this retrospective study, it was aimed
      to compare the cases of capitonnaged and not capitonnaged thoracal hydatid cysts
      with regard to hospital stay and post-operative chest tube removal day. Documents
      of 15 patients operated for pulmonary hydatid cysts in our clinic were reviewed.
      In 7 cases pericystectomy and removal of germinative membrane was performed
      whereas in 8 patients capitonnage was added to the procedure. In all cases open
      airways were suture controlled and pleural cavity was drained with chest tube
      connected to waterseal system. Average hospital stay of capitonnaged cases was 8
      days and of uncapitonnaged ones was 12 days. Thoracal drainage tubes were removed
      in an average of 4 post-operative days in capitonnaged cases and of 7 days in the
      others. Statistical analysis were made by Mann-Whitney U test. Difference between
      the hospital stays of the 2 groups were not significant, whereas it was
      significant statistically between chest tube removal days (p<0.05). Capitonnage
      shortens postoperative chest tube drainage period in pulmonary hydatid cysts,
      resulting in lower morbidity compared with the uncapitonnaged cases.

PMID- 11343560
TI  - Prophylactic intracavitary (pneumonectomy space) antibiotic instillation: a
      comparative study.
AB  - BACKGROUND AND OBJECTIVES: Postpneumonectomy empyema is a dreaded complication of
      pneumonectomy. The effectiveness of prophylactic intracavitary antibiotic
      instillation is not known. We conducted a retrospective review to assess the
      effect of pneumonectomy space antibiotic instillation on septic complications
      (empyema and bronchial fistula) of pneumonectomy. METHODS: Ninety-three
      consecutive patients underwent pneumonectomy at our institution over a three-year
      period. Their charts were reviewed retrospectively and data was collected on age,
      gender, diagnosis, intravenous antibiotics, intracavitary (pneumonectomy space)
      antibiotics, empyemas, bronchial fistulas, length of hospital stay, and operative
      mortality. RESULTS: All 93 patients received 3 perioperative doses of
      prophylactic intravenous antibiotics. One group (n=47) of patients also received
      intraoperative intracavitary instillation of an antibiotic solution (penicillin
      G: 5 million units, bacitracin: 50,000 units, gentamicin: 60 mg, in 1 litre of
      saline) while the other group (n=46) did not. Age, gender, diagnosis, and length
      of stay were not significantly different in the two groups. There were no
      empyemas or bronchial fistulas in the intracavitary antibiotic group.
      Postpneumonectomy empyemas occurred in 6 (13%) patients (empyema with bronchial
      fistula: 5, empyema alone: 1) that had not received intracavitary antibiotics
      (p=0.012). There were 4 deaths (9%) in each group (p=0.63). CONCLUSIONS:
      Prophylactic intraoperative intracavitary antibiotic instillation may reduce the
      incidence of empyemas after pneumonectomy. However, a randomized trial would be
      needed to prove the effectiveness of this form of prophylactic antibiotic
      strategy.

PMID- 11343561
TI  - Assessment of the effectiveness of descending aortomyoplasty for nonischemic
      cardiac failure by means of the subendocardial viability index.
AB  - INTRODUCTION: Paraaortic or external aortic counterpulsation is been investigated
      as a definitive ventricular assistance in cases of terminal congestive heart
      failure and when heart transplantation is counterindicated. Our aims is to assess
      the haemodynamic effects of an descending aortomyoplasty in a biological model of
      congestive heart failure. MATERIALS AND METHODS: As specimens, we used 10 "Large
      White" pigs. Mean weight was 25,3+/-2,14 Kg. After the administration of
      conventional anaesthesia, dissection of the latissimus dorsi muscle was
      performed. Then we performed a thoracotomy at the level of the fourth intercostal
      space to reach the thoracic aorta. The aorta is dissected 7 centimetres from the
      output of the subclavia artery and it is wrapped by the dissected muscle. A
      cardiomyostimulator is provided in order to allow the synchronization between the
      diastole and the muscle contraction. The model of heart failure was provoked
      using Verapamil plus Propanolol i.v. RESULTS: A significant increase of the
      systolic and diastolic aortic pressure (54,2+/-4,05 and 27.5+/-6.77 mmHg versus
      76.5+/-6.25 and 56.4+/-5.2 mmHg, p<0,001) and a significant decrease of the left
      ventricle telediastolic pressures were observed (12.9+/-9 versus 2.6+/-1.57 mmHg,
      p<0,001). An increase of the cardiac output (0.363+/-0.11 versus 0.846+/-0.08
      L/min, p<0,001) and the Subendocardial Viability Index (0.968+/-0.076 versus
      1.351+/-0,107, p<0,001)were observed in a model of non-ischemic heart failure.
      CONCLUSION: Descending Aortomyoplasty as a technique to support circulation in
      cases of acute heart failure, improves the parameters of ventricular function,
      aiding the functional recovery of the left ventricle and improving significantly
      cardiac output as well as diastolic and systolic cardiac pressure. In addition to
      this, improves the Subendocardial Viability Index in cases of acute heart
      failure, which indirectly reflects an improvement of the Transmural and
      Subendocardial Perfusion of the failing heart.

PMID- 11343562
TI  - Slow induction of milrinone after coronary artery bypass grafting.
AB  - The aim of this study was to evaluate the hemodynamic effects of a slow induction
      of milrinone after open heart surgery. Twenty patients who underwent elective
      coronary artery bypass grafting were randomized into two groups, with 10 patients
      receiving a continuous infusion of milrinone (5 microg/kg/min) (group M), and 10
      patients undergoing treatment without milrinone (group C). This is a preliminary
      study for evaluating the efficacy of a slow induction of milrinone, so patients
      in low cardiac output state were excluded. A continuous infusion without an
      initial loading dose was initiated in the intensive care unit. Hemodynamic
      parameters and the concentration of milrinone were measured 90 minutes and 3
      hours after initiation of the milrinone infusion. A significant decrease in
      arterial pressure occurred at 3 hours in group M, and both the systemic vascular
      resistant indices decreased significantly (p<0.05) at 90 minutes. No significant
      changes occurred in group C. Cardiac index and heart rate increased significantly
      (p<0.05) in group M, but were unchanged in group C. No significant change in
      double product was observed in either group. Hypotension (systolic blood pressure
      less than 100 mmHg) or arrhythmia did not occur in group M. The concentration of
      milrinone at 90 minutes and 3 hours was 97+/-22 and 124+/-27 ng/ml, respectively.
      A slow induction of milrinone is safe and effective in patients following cardiac
      surgery.

PMID- 11343563
TI  - Coronary artery bypass grafting within 30 days of an acute myocardial infarction.
AB  - Early surgical intervention is now often considered for symptomatic patients
      after an acute myocardial infarction. Conversely coronary artery bypass grafting
      soon after an acute myocardial infarction poses substantial risks. The present
      study was performed to evaluate the results of Coronary artery bypass grafting
      soon after an acute myocardial infarction. METHODS: From November 1991 to
      November 1999, 478 consecutive patients underwent coronary artery bypass grafting
      and 68 of these underwent an operation within 30 days of AMI. The data of these
      patients were analyzed retrospectively. Univariate and multivariate analyses of
      many variables were performed regarding operative mortality. RESULTS: Operative
      mortality (7.4%) was significantly higher in the patients with an acute
      myocardial infarction than in the patients without it (0.8%) during the same
      period as the subjects of this study. Coronary artery bypass grafting without
      arterial grafts was solely determined to be the predictor of survival. The
      survival curve demonstrated better long-term results in patients undergoing
      bypass grafting with arterial grafts than in patients undergoing bypass grafting
      with venous grafts alone. CONCLUSIONS: If hemodynamic conditions can not be
      stabilized, then coronary artery bypass grafting using arterial grafts, when
      indicated, should be performed even early after AMI.

PMID- 11343564
TI  - Based on acute outcomes, "all arterial" coronary bypass surgery should be
      performed on younger elective patients.
AB  - OBJECTIVES: This study evaluated acute results as a function of the number of
      arterial conduits used to compare procedural differences and the subsequent
      effects on acute outcomes in selected patient populations. BACKGROUND: All
      arterial operations may provide better long-term results for younger patients
      undergoing coronary bypass surgery (CABG). However, concerns regarding additional
      morbidity when using multiple arterial conduits have inhibited their use.
      METHODS: The study comprised a retrospective review of patients (2,586)
      undergoing CABG. Group 1 consists of single artery vein graft (1,755). Group 2:
      two arteries were used in addition to vein grafts (209). Group 3: three or more
      arterial conduits were used, with or without vein grafts (116). Group 4: only
      vein grafts were used (506). RESULTS: Patients undergoing primarily arterial
      procedures, Group 2 and 3, were younger, had a better exercise profile, less
      history of myocardial infarction (MI), had less left ventricular dysfunction.
      There were also fewer emergencies, co-morbidities and associated procedures in
      this group. The cardiopulmonary bypass and cross clamp times were longer in those
      procedures with three or more arteries; however, this difference was only
      thirteen and fourteen minutes, respectively. Post-operative complications were
      higher in patients in the vein only group. The hospital stay and mortality was
      equivalent among groups in which an arterial bypass was used and better than
      those in which only vein grafts were used. CONCLUSIONS: For younger patients,
      "all arterial operations," require only minimal increases in ischemic and
      operative times, which do not affect acute outcomes.

PMID- 11343565
TI  - Case report: right subclavian artery pseudoaneurysm due to perforation of
      esophageal cancer.
AB  - A 51-year-old man presented with massive hematemesis. Perforation of upper
      esophageal cancer, which had already occurred at least six days earlier,
      progressed to upper mediastinitis. The mediastinitis contiguous to the right
      subclavian artery was considered to have caused a pseudoaneurysm. Rupture of the
      pseudoaneurysm into the esophagus resulted in massive hematemesis. Both enhanced
      computed tomography and angiography were diagnostic for the pseudoaneurysm.
      Transluminal endovascular stent-grafts placement was successful in preventing
      subsequent hemorrhage.

PMID- 11343566
TI  - Spontaneous pneumothorax: a rare complication of miliary tuberculosis.
AB  - Pneumothorax is a rare complication of miliary tuberculosis. In this report, a 25
      year old patient developing pneumothorax while on the treatment for miliary
      tuberculosis treatment is presented and the related literature has been reviewed.
      Pneumothorax, although rare, should be considered when a patient with miliary
      tuberculosis develops a sudden, severe pain on either side of the chest with
      breathlessness. The treatment should be tailored according to the size of
      pneumothorax either pleural drainage through chest tube or needle aspiration.
      Meanwhile, antituberculous treatment should be continued without interruption.

PMID- 11343567
TI  - Bronchospasm induced by cardiopulmonary bypass.
AB  - Severe bronchospasm during cardiopulmonary bypass (CPB) is an unusual event. A 16
      year-old girl with pulmonary stenosis who underwent reconstruction of the right
      ventricle outflow tract experienced severe bronchospasm following CPB. Just after
      the initiation of the partial CPB, high inspiratory airway pressure was suddenly
      recognized. The lung had become too stiff for the anesthetic circuit bag to be
      squeezed by hand. Tracheobronchial obstruction was ruled out by investigation
      with a fiberoptic bronchoscope. A presumptive diagnosis of severe bronchospasm
      was made, and aggressive bronchodilator therapy was instituted. The attack was
      successfully treated with aggressive bronchodilator therapy. Although the exact
      causes for bronchospasm in our case are not clear, CPB factors, such as the
      release of complements and allergic reactions might have induced the attack under
      relatively light anesthetic state.

PMID- 11343568
TI  - Patch reconstruction of the mitral annulus for active infective endocarditis with
      annular abscess.
AB  - Active infective endocarditis is associated with high operative mortality and
      morbidity. The outcome may be improved by operating at the optimal time using the
      most appropriate surgical procedure. We describe a 15-year-old man with active
      infective endocarditis of the mitral valve associated with an annular abscess.
      Disseminated intravascular coagulation was associated with progressive decrease
      in the platelet count. The abscess was debrided, the mitral annulus was patch
      reconstructed using bovine pericardium treated with glutaraldehyde, then the
      mitral valve was replaced. The patient was discharged from intensive care unit 3
      days after operation with clinical and blood examination improvement. The patient
      is being observed carefully by periodic follow-up echocardiography, and there is
      no evidence of PVD, PVE or calcification of the patch during 14 months of follow
      up period. Patch reconstruction of the annulus using bovine pericardium treated
      with glutaraldehyde reinforced the annulus and prevented local reinfection of the
      prosthesis in this patient.

PMID- 11343569
TI  - A case of a chronic traumatic thoracic aneurysm 11 years after injury.
AB  - A 28-year-old male, who was involved in an automobile accident 11 years
      previously, was diagnosed as having a chronic traumatic thoracic aneurysm. An
      enhanced computed tomographic scanning (CT) and three-dimensional CT demonstrated
      that a thoracic aortic aneurysm of 50 mm in the maximal axis was located at the
      aortic isthmus and dilated posteriorly. He underwent thoracic aorta graft
      replacement using Femoro-femoral partial bypass. The surgery was successful and
      the postoperative course was uneventful.

PMID- 11343570
TI  - Endoluminal stent-grafting for thoracoabdominal aortic aneurysm in Takayasu's
      disease.
AB  - We report a case with occlusion of multiple branches of the aorta and a
      pseudoaneurysm due to rupture of a severely calcified non-aneurysmal
      thoracoabdominal aorta in a patient with Takayasu's disease. The patient was
      successfully treated by endoluminal stent-grafting without mesenteric ischemia.

PMID- 11343571
TI  - Ultrasonic pleural debridement of empyema.
AB  - Thoracic decortication is a common procedure for empyema. However, effective
      dissection without injuring the lung parenchyma is sometimes difficult. We
      introduce a new technique using an ultrasonic surgical unit (USUTM) to search the
      dissection plane and simultaneously perform pleural debridement and irrigation
      with minimal injury of the lung parenchyma. USUTM was used on 5 patients with
      acute empyema with fibrino-purulent phase and good clinical course was achieved.
      This procedure facilitates effective pleural debridement under either
      thoracoscopy or conventional thoracotomy.

PMID- 11343572
TI  - The International Journal of Neuropsychopharmacology.
AB  - Almost half a century ago, a series of remarkable therapeutic developments
      occurred and were soon recognised as milestones in the history of medicine. The
      introduction of lithium, chlorpromazine, imipramine and the monoamine oxidase
      inhibitors, within a few years of each other, radically altered the prospects for
      treating serious psychiatric disorders. Until then, electroconvulsive therapy had
      been the only definitive treatment available. Research on pharmacological agents
      that alleviate disturbances of mood, cognition and behaviour, was given an
      impetus that led to quantum expansion in the ensuing years. It has become
      customary to recount the history of neuropsychopharmacology from that time.
      Although this is an understandable bias, it ignores much fundamental research in
      neurophysiology, neurochemistry and pharmacology and clinical experimentation
      with psychoactive agents that laid the foundations for what was to follow.
      Nevertheless, neuropsychopharmacology is still a very young discipline. This
      manifests not only in chronology but in the ferment, rapid shifts in priorities
      and fluidity of fundamental concepts that are hallmarks of youth. The critical
      observer cannot but concede the likelihood that tenets held basic to contemporary
      neuropsychopharmacology could turn out to be substantially overemphasised,
      unacceptably simplistic or even incorrect, in the relatively near future. Perusal
      of major papers in the field, published no more than one or two decades ago,
      confirms this impression. Rather than detracting from the discipline, these
      attributes are what give neuropsychopharmacology its remarkable allure. There is
      the distinct feeling that much of what can be known has yet to be discovered.
      Steps equal to or greater in impact than those of half a century ago, wait to be
      taken.

PMID- 11343573
TI  - Progressive attenuation of the firing activity of locus coeruleus noradrenergic
      neurons by sustained administration of selective serotonin reuptake inhibitors.
AB  - Sustained administration of the selective serotonin (5-HT) reuptake inhibitors
      (SSRIs) citalopram for 2, 14, and 21 d, and paroxetine for 2 and 21 d (20 and 10
      mg/kg.d, respectively, s.c. using osmotic minipumps) produced a gradual decrease
      in spontaneous firing activity of locus coeruleus (LC) noradrenergic neurons. In
      contrast, sustained desipramine administration for 2 and 21 d (10 mg/kg.d)
      robustly reduced LC firing activity, though only to the same extent, following
      these two treatment periods. The enhancement of the firing rate of LC neurons
      produced by the 5-HT1A agonist 8-OH-DPAT (10-50 &mgr;g/kg, i.v.) in desipramine-
      and citalopram-treated rats was abolished, indicating a desensitization of 5-HT1A
      receptors. However, the attenuation of the firing rate of LC neurons induced by
      the 5-HT2 agonist DOI (5-50 &mgr;g/kg, i.v.) was decreased approx. 2-fold in
      citalopram-treated rats but not significantly altered in desipramine-treated
      rats. Since 5-HT neurons exert a tonic inhibitory effect on LC neurons, it
      appears that enhancing 5-HT neurotransmission by sustained SSRI administration
      leads to a reduction of the firing rate of noradrenergic neurons. In conclusion,
      SSRIs attenuate the activity of noradrenergic neurons with a delay that is
      consistent with their beneficial effect in depression and some anxiety disorders,
      such as panic, generalized and social anxiety disorders. However, given the
      hyperadrenergic state often observed in anxiogenic conditions the latter
      phenomenon is believed to contribute more to the anxiolytic effect of SSRIs than
      to their antidepressant action.

PMID- 11343574
TI  - Chronic antipsychotic treatment selectively alters nerve growth factor and
      neuropeptide Y immunoreactivity and the distribution of choline acetyl
      transferase in rat brain regions.
AB  - Neuropeptides and neurotrophins play a number of roles in the central nervous
      system (CNS). Nerve growth factor (NGF), the first characterized member of the
      family of neurotrophins, influences the synthesis of some neuropeptides,
      including neuropeptide Y (NPY), a peptide amply expressed in the CNS, interacting
      with catecholamines and modifying behaviour. In this study we investigated
      whether antipsychotic treatment affects the constitutive levels of NGF-, NPY- and
      choline acetyl transferase (ChAT)-like immunoreactivities (-LI) in the CNS. Rats
      were fed food supplemented with haloperidol (1.15 mg/100 g food), risperidone
      (1.15 or 2.3 mg/100 g food), or vehicle. After 29 d treatment animals were
      sacrificed with focused high-energy microwave irradiation for radioimmunoassay
      (RIA) of NPY-LI, by decapitation for analysis of NGF, and by perfusion for
      immunocytochemistry. Haloperidol and risperidone elevated NGF-LI concentrations
      in the hypothalamus but decreased NGF-LI in the striatum and hippocampus. In
      contrast, antipsychotics did not alter NPY-LI in the striatum. Haloperidol
      increased NPY-LI concentration in the occipital cortex, while risperidone
      increased NPY-LI in the occipital cortex, hippocampus, and hypothalamus.
      Significant decreases in ChAT immunoreactivity in large-size neurons following
      both haloperidol and risperidone treatments in the septum as well as Meynert's
      nucleus were observed. Our findings demonstrate that antipsychotic drugs alter
      the regional brain levels of NGF-LI, NPY-LI and ChAT-LI and raise the possibility
      that these effects are implicated in their pharmacological and therapeutic
      properties.

PMID- 11343575
TI  - Behavioural effects of NKH-477, a forskolin analogue, on locomotion and rearing
      in rats.
AB  - NKH-477 is a water-soluble analogue of forskolin that stimulates adenylate
      cyclase and has antidepressant properties in the forced swim model of depression.
      The effect of chronic NKH-477 on locomotion and rearing and its behavioural
      interaction with lithium and inositol was tested. NKH-477 (1.5 mg/kg),
      administered acutely or chronically for 9 d to rats, induced a significant
      reduction in locomotor behaviour and rearing. In a second experiment, rats were
      pretreated with chronic dietary lithium, inositol or control diet for 3 wk before
      being injected with either saline or NKH-477. Inositol had no effect on the
      decreased locomotion and rearing induced by NKH-477. There was a significant, but
      transient, interaction between lithium and NKH-477 on rearing on the second and
      third days of treatment. The lithium group had lower baseline rearing than
      control or inositol-treated rats, and was not further affected by NKH-477
      treatment. This is the first report of a marked effect of this forskolin analogue
      on locomotion and rearing, with no tolerance in the time frame examined. The
      interaction between NKH-477 and lithium suggests that the well-documented ability
      of lithium to inhibit stimulation of the cAMP system is relevant to its
      behavioural effects; however, the transient nature of this interaction, suggests
      that other biochemical mechanisms are involved in the behavioural effects of
      lithium.

PMID- 11343576
TI  - Dopaminergic drug response and the genotype (Taq IA polymorphism) of the dopamine
      D2 receptor.
AB  - The genotype of the receptor with which a particular drug interacts may be a
      between- subject factor that modifies the pharmacodynamic and consequently the
      therapeutic response to drugs. Subjects with A1 allele (Taq IA restriction
      fragment length polymorphism) of the gene encoding for the dopamine D2 receptor
      (DRD2) seem to express lower number of DRD2 compared to subjects who do not have
      this allele. We investigated whether subjects homozygous for the A1 allele of the
      DRD2 gene have decreased response to DRD2 stimulation by apomorphine when
      compared with those homozygous for the A2 allele. Two hundred and two Caucasian
      subjects were genotyped for DRD2 Taq IA polymorphism, 6.9 % had the genotype A1A1
      and 65% A2A2. Nine homozygous subjects/group were selected for the apomorphine
      study. Five, 10 and 20 &mgr;g/kg of apomorphine were administered subcutaneously
      according to a randomized crossover design. The main pharmacodynamic criterion
      was the plasma growth hormone increase induced by apomorphine. Secondarily, we
      measured oral temperature responses and yawns in response to apomorphine. Plasma
      apomorphine concentrations were similar for the two matched and only
      genotypically different groups. Apomorphine dose-dependently increased serum
      growth hormone concentration, and significant effect of time, dose by time
      interaction but no effect of genotype or genotype by dose interaction was shown.
      Apomorphine decreased body temperature, significant effect of dose, time, dose by
      time interaction but no effect of genotype or genotype by dose interaction were
      observed. The number of apomorphine-induced yawns increased dose-dependently but
      no significant difference between groups occurred. Thus, in this study
      apomorphine-induced responses were not modified by DRD2 Taq IA polymorphism
      although the power of the study could be insufficient to detect subtle
      differences.

PMID- 11343577
TI  - Relapses in bipolar patients: changes in social rhythm?
AB  - The Ramadan month represents a valuable opportunity to test the hypothesis that
      the course of the illness of bipolar patients can be disrupted by the change in
      social rhythm which usually occurs during this month. The objectives of this
      study were to follow up the mood state and blood lithium level of fasting Muslim
      bipolar patients who had been on lithium therapy for at least 3 months, and were
      clinically stable before being included in the study. Twenty bipolar patients
      were enrolled during the month of Ramadan in 1997. Diagnosis of bipolar disorder
      was according to ICD-10 criteria. Patients were assessed during the week before
      Ramadan, the second and the fourth weeks of the fasting month and the first week
      after its end, with the Hamilton Depression and Bech-Rafaelsen scales. The plasma
      concentration of lithium was also assessed. The main finding of the study was
      that 45% of the patients relapsed, 70% during the second week and the remaining
      patients at the end of Ramadan. These relapses were not related to plasma
      concentration of lithium. Most of the relapses were manic (71.4 %). Patients who
      did not relapse had insomnia and anxiety during the second and third weeks of the
      study. Side-effects of lithium increased and were observed in 48% of the sample,
      mostly dryness of the mouth with thirst and tremor. The result of this pilot
      study indicates that the Ramadan month may disrupt the mood state of bipolar
      patients. More studies are needed to confirm this observation and to evaluate the
      validity of the Ramadan model to study the impact of social rhythms on bipolar
      patients.

PMID- 11343578
TI  - Overdose profiles of new antipsychotic agents.
AB  - Although the more recently introduced antipsychotic drugs are increasing in
      popularity, the pattern of symptomatology when taken in overdose is not well
      defined. We monitored all enquiries to the National Poisons Information Service,
      London (NPIS, London) concerning antipsychotic drugs over a 9-month period in
      1997 and report our findings concerning four drugs (olanzapine, clozapine,
      risperidone and sulpiride). All overdoses involving a single agent were followed
      up by a letter to the enquirer requesting details and outcome of the case.
      Although a total of 574 enquiries involving the selected antipsychotic drugs were
      received, only 45 of these cases involved overdose with a single agent. There
      were no fatalities or cases of convulsions in the series. Cardiac arrhythmias
      were only noted with sulpiride. Symptoms were most marked with clozapine, with a
      majority of patients experiencing agitation, dystonia, central nervous system
      (CNS) depression and tachycardia. Olanzapine and sulpiride produced a range of
      different symptoms, while most patients who had taken risperidone were
      asymptomatic. Monitoring poisons centre enquiries is a useful way of comparing
      overdose toxicities. We conclude that at least two of the novel antipsychotic
      agents, olanzapine and risperidone, appear to have a favourable overdose profile,
      which suggests that they are safer in overdose than the phenothiazines and
      butyrophenones.

PMID- 11343579
TI  - Fluoxetine augmentation in citalopram non-responders: pharmacokinetic and
      clinical consequences.
AB  - In an open trial 11 in-patients with a major depressive episode (ICD-10),
      extensive metabolizers of mephenytoin (CYP2C19) and dextromethorphan (CYP2D6) and
      who were non-responders to a 3-wk pretreatment with 40 mg/d citalopram (Cit),
      were co-medicated for 7 wk (days 0-49) with fluoxetine (Fluox) (10 mg/d). Plasma
      concentrations of S-Cit and R-Cit significantly increased from day 0 (means+/
      S.D.: 28+/-9 and 47+/-11 &mgr;g/l, respectively) to day 49 (58+/-12 and 72+/-21
      &mgr;g/l, respectively) (p & 0.01 for each comparison), and the S-Cit/R-Cit ratio
      increased from 0.61+/-0.16 to 0.82+/-0.12 (p & 0.01). Therefore, Fluox increases
      the pharmacologically more active S-Cit (in comparison with R-Cit) with some
      stereoselectivity, most probably by inhibition of CYP2D6 and CYP3A4. Eight of the
      11 patients showed clinical improvement (reduction > 50% of the MADRS score) and
      the combined treatment was generally well tolerated.

PMID- 11343580
TI  - Homozygosity for the Gly-9 variant of the dopamine D3 receptor and risk for
      tardive dyskinesia in schizophrenic patients.
AB  - This study was undertaken to re-examine whether homozygosity for the Gly-9
      variant (allele 2) of the dopamine D3 receptor gene (DRD3) is associated with
      increased risk for tardive dyskinesia (TD) in schizophrenic patients. Seventy-one
      antipsychotic-treated subjects with schizophrenia from Newcastle upon Tyne, UK,
      were genotyped for the presence of allele 1 (Ser-9) and allele 2 (Gly-9) of the
      dopamine D3 receptor (DRD3) Ser-9-Gly polymorphism. Among 32 patients with TD, 7
      subjects (22 %) were homozygous for the Gly-9 variant (2-2 genotype), whereas 4
      out of 39 patients (10 %) without TD had this genotype. The non-significant
      tendency in this sample towards an over-representation of allele 2 and the 2-2
      genotype among schizophrenic patients with TD is in line with our initial report
      as well as recent studies by others, indicating that the Gly-9 allele of DRD3 may
      be a susceptibility factor for the development of TD in neuroleptic-treated
      individuals with schizophrenia. There are, however, some recent non-supportive
      reports, and since the trend in our present study failed to reach statistical
      significance, further studies on larger samples and future meta-analysis may be
      necessary to establish the role of the DRD3 in the pathogenesis of TD.

PMID- 11343581
TI  - Serotonergic gene transcriptional control regions: targets for antidepressant
      drug development?
AB  - The formation and integration of neural networks is dependent on the actions of
      the master control neurotransmitter serotonin (5-HT) acting through multiple 5-HT
      receptor subtypes. During brain development 5-HT regulates morphogenetic
      activities, such as neural differentiation, axon outgrowth, and configuration of
      synaptic connections. In the adult brain, midbrain raphe serotonergic neurons
      project to a variety of brain regions and modulate a wide range of physiological
      functions. Several lines of evidence indicate that genetically determined
      variability in serotonergic gene expression influences complex behaviour and may
      lead to conditions with increased anxiety, depression, and aggression.
      Investigation of the regulation of serotonergic gene transcription and its impact
      on neural development and plasticity will spur general interest to identify
      serotonergic gene-related molecular factors underlying disease states and to
      develop more effective treatment strategies. Gene targeting strategies have
      increasingly been integrated into investigations of brain function and along with
      the fading dogma of a limited capacity of neurons for regeneration,
      reproducibility, and plasticity, it is realized that gene transfer techniques
      using efficient viral vectors in conjunction with neuron-selective
      transcriptional control systems may also be applicable to complex disorders of
      the brain. Given the fact that the 5-HT system continues to be an important
      target for large-scale drug development and production, novel strategies aiming
      toward the modification of 5-HT function at the level of gene expression are
      likely to be exploited by enterprises participating actively in the introduction
      of alternative therapeutic approaches.

PMID- 11343582
TI  - Olanzapine treatment in an organic hallucinosis patient.
AB  - A.L., a 42-yr-old man has been in treatment at our out- patient clinic since 1992
      suffering from psychotic manifestations following a second severe closed-head
      injury. The patient had his first contact with a psychiatrist 3 yr after his
      first severe head injury in 1962 (when 10 yr old). During his first
      hospitalization (in 1994) he presented with signs of affective flattening and
      behavioural problems and indications of borderline intellectual functioning or
      mild mental retardation. The patient underwent several surgical interventions.
      The early inter-operative period was complicated by behavioural problems and a
      lack of motivation. At that time his intellectual tests (WAIS) showed a decline
      of results to a level of 60-80 in verbal tests, with a significant decrease in
      performance results. However, after further surgery, his intellectual condition
      improved enabling him to complete a secondary-school education, get married and
      start work as an industrial worker. From that time onwards he had no contact with
      psychiatrists, nor did he receive any medication treatment.

PMID- 11343583
TI  - Prediction of lithium response by 31P-MRS in bipolar disorder.
AB  - Lithium is still the first drug of choice for treatment of bipolar disorder.
      However, it is also evident that a certain proportion of patients with bipolar
      disorder do not respond to maintenance treatment with lithium. If predictors of
      lithium response could be identified before initiation of maintenance treatment,
      it would help in selecting an appropriate mood stabilizer to minimize the risk of
      relapse. Many clinical predictors of positive lithium response have been
      reported. These include pure classical mania, psychotic features, small number of
      episodes, positive family history, lower scores of neuroticism, and patterns of
      course-of-illness (Carroll, 1979; Maj et al., 1989, for review). However, these
      variables still cannot completely predict lithium response. Few pharmacological
      or biochemical predictors of lithium response have been reported. High red blood
      cell :plasma lithium ratio, which reflects compliance, has been reported to be
      associated with positive response (Harvey and Kay, 1991). A possible genetic
      marker for lithium response, the C973A polymorphism in the inositol polyphosphate
      1-phosphatase gene, has been reported (Steen et al., 1998), although it has not
      yet been replicated.

PMID- 11343584
TI  - Drugs, the Brain, and Behavior: the Pharmacology of Abuse and Dependence. Edited
      by John Brick and Carlton Erickson. 186 pp., illustrated. New York: Haworth
      Medical Press.

PMID- 11343585
TI  - Role of maternal biochemistry in fetal brain development: effect of maternal
      thyroidectomy on behaviour and biogenic amine metabolism in rat progeny.
AB  - Few studies have addressed the role of biochemicals of maternal origin on fetal
      neurodevelopment and behavioural outcome. Thyroid deficiency in the
      thyroidectomized pregnant rat provides an excellent model to study fetal effects
      of maternal chemistry, as this condition is known to be associated with deficits
      in motor and cognitive behaviour in human offspring. Based on evidence that
      thyroid hormone of maternal origin may be an important determinant in regulating
      these behaviours, we assessed neurobehaviours and regional brain biogenic amine
      levels in offspring of rats thyroidectomized (Tx) prior to conception. Cross
      fostering techniques were used to isolate fetal effects of maternal thyroid
      deficiency from possible neonatal effects during nursing by thyroid-deficient
      dams. The progeny of Tx dams showed significant deficits in maze learning, were
      less cautious in emotionality testing, and were more active in open-field
      exploration. Tx females appeared to be more vulnerable to the effects on
      learning. Learning in Tx males was only slightly impaired. Serotonin and dopamine
      metabolism was also affected in a brain region-specific manner in Tx progeny.
      Levels of 5-HIAA were reduced in the olfactory tubercle and cortex. HVA levels
      were lower in olfactory tubercle, but were elevated in the hippocampus. As these
      neurotransmitters play a functional role in activity, mood and learning, the
      findings may be pertinent to the observed behavioural impairments. The results
      are consistent with the hypothesis that an adequate in utero thyroid hormone
      environment may be essential for early fetal neurodevelopment even if the fetus
      is euthyroid.

PMID- 11343586
TI  - Effects of a benzodioxan derivative MKC-242 on the firing activity of the dorsal
      hippocampus CA1 pyramidal neurons in awake and urethane- anaesthetized rats: in
      vivo electrophysiological evidence for a 5-HT 1A agonistic property.
AB  - The aim of the present in vivo study was to determine whether a benzodioxan
      derivative MKC-242, (S)-5-[3-[(1,4-benzodioxan-2-ylmethyl)amino]propoxy]-1,3
      benzodioxole hydrochloride, possesses an agonistic activity at postsynaptic
      serotonin (5-HT)1A receptors in the rat hippocampus when administered
      systemically. We examined the effects of acute administrations of MKC-242 on the
      firing activities of dorsal hippocampus CA1 pyramidal neurons. In quiet awake
      rats, s.c. administrations of MKC-242 significantly decreased the spontaneous
      firing activity in a dose-dependent manner at doses of 0.3-6 mg/kg. In urethane
      anaesthetized rats, i.v. injections of MKC-242, at cumulative doses of 0.3-3
      mg/kg, also significantly and dose-dependently inhibited the firing activity
      induced by microiontophoretically applied quisqualate. These decreasing effects
      were antagonized by the selective 5-HT1A antagonists WAY-100135 (5 mg/kg, s.c.)
      and WAY-100635 (0.2 mg/kg, s.c. to the awake rats and 0.4 mg/kg, i.v. to the
      anaesthetized rats), thereby confirming that MKC- 242 decreased the firing
      activities by stimulating 5-HT1A receptors. The selective depletion of 5-HT
      produced by the 3-d administration of the 5-HT synthesis inhibitor,
      parachlorophenylalanine (500 mg/kg.d, i.p.), did not affect the decreasing effect
      of MKC-242 in the awake animals, indicating that postsynaptic 5-HT1A receptors
      mediated the decreasing effect. The present results provided the first in vivo
      electrophysiological evidence that MKC-242, when systemically administered,
      exerts a 5-HT1A agonistic action at the postsynaptic level.

PMID- 11343587
TI  - Post-mortem studies of brain phosphatidylinositol hydrolysis in depression and
      the effect of antidepressant treatment.
AB  - Basal, neurotransmitter and G protein-mediated [3H]PI hydrolysis was measured in
      the frontal cortex, temporal cortex, hippocampus and thalamus from suicides, with
      a firm retrospective diagnosis of depression, and individually matched controls.
      Suicides were divided into those who had been free of antidepressant drugs for at
      least 3 months and those in whom prescription of antidepressants was clearly
      documented. There were no significant differences in basal, GTP?S-, 5-HT- or ACPD
      stimulated [3H]PI hydrolysis in either antidepressant- free or antidepressant
      treated suicides and their respective controls in the four brain regions studied.
      This was also the case when suicides were divided into those dying by violent or
      non-violent means. The two main conclusions from this study are: (i)
      neurotransmitter- (5-HT and ACPD) stimulated [3H]PI hydrolysis was unaltered in
      depression, and (ii) antidepressant treatment did not modify PI-mediated signal
      transduction.

PMID- 11343588
TI  - Midazolam decreases cerebral blood flow in the left prefrontal cortex in a dose
      dependent fashion.
AB  - Midazolam, a short-lived benzodiazepine producing sedation and reversible
      anterograde amnesia, was administered intravenously to 14 healthy male
      volunteers. Regional cerebral blood flow (rCBF) was measured using positron
      emission tomography (PET) with intravenous H2 15O at either a 'high' midazolam
      EEG effect (EEG signs of stage 2 sleep), or 'low' midazolam EEG effect (increase
      in EEG beta power only). Memory tests administered following PET scans showed
      significant drug-induced impairment in learning and retrieval at the same drug
      concentration at which PET images were acquired. Statistical parametric mapping
      was used to identify regions where rCBF changes after drug administration were
      significantly different in the high- vs. low- effect groups. Dosexcondition
      interactions were found in the left dorsolateral prefrontal cortex [Brodmann's
      areas (BA) 9 and 46], bilateral orbital-frontal cortex (BA 47), the left middle
      temporal gyrus (BA 22) and the right hippocampus. The predominantly left frontal
      rCBF decreases occur in a region associated with semantic processing, working
      memory, and encoding of verbal material, a process preferentially affected by
      midazolam. Our interpretation is that rCBF changes in the hippocampus are
      unlikely to mediate the anterograde amnesia produced by midazolam. Although in
      the present study PET images were acquired during the resting state rather than
      during memory processing, these results underscore the need for further
      investigation relating to the interaction of midazolam with specific cognitive
      operations in these brain regions.

PMID- 11343589
TI  - Comparison of unlimited numbers of rapid transcranial magnetic stimulation (rTMS)
      and ECT treatment sessions in major depressive episode.
AB  - Repetitive transcranial magnetic stimulation (rTMS) is a new technology which
      holds promise as a treatment of psychiatric disorders. Most work to date has been
      on depression. Superiority to placebo has been indicated in three small blind
      studies. We compared the antidepressant effects of rTMS and ECT in 32 patients
      suffering major depressive episode (MDE) who had failed to respond to at least
      one course of medication. There was no limit to the number of treatment sessions
      which could be given and treatment was continued until remission occurred or
      response plateaued. A significant main effect for treatment type was found
      [Pillai trace = 0.248, F(3,28) = 3.076, p = 0.044; power = 0.656], reflecting an
      advantage for ECT patients on measures of depression overall, however, rTMS
      produced comparable results on a number of measures. Blind raters using the 17
      item Hamilton Depression Rating Scale (HDRS) found the rate of remission (HDRS =
      ? 8) was the same (68.8%), and the percentage improvement over the course of
      treatment of 55.6% (rTMS) and 66.4% (ECT), while favouring ECT, was not
      significantly different. Significant differences were shown (p & 0.03) in
      percentage improvement on Beck Depression Inventory ratings (rTMS, 45.5%; ECT,
      69.1%), but not for improvement in Visual Analogue ratings of mood (rTMS 42.3%;
      ECT, 57%). rTMS has antidepressant effects of useful proportions and further
      studies are indicated.

PMID- 11343590
TI  - Open trial of citalopram in adults with post-traumatic stress disorder.
AB  - The selective serotonin reuptake inhibitors (SSRIs) are rapidly emerging as
      preferred first-line drugs in the pharmacological management of post-traumatic
      stress disorder (PTSD). Citalopram, an SSRI with highly potent and selective
      serotonin reuptake inhibition, may be a useful agent for treating the intrusive,
      avoidance, and arousal symptoms that characterize PTSD. Fourteen adult subjects
      (12 with civilian-related post-traumatic stress disorder, and 2 with combat
      related post-traumatic stress disorder) were entered into an 8 wk, open- label,
      fixed-dose trial of citalopram, commencing with 20 mg/d, and increasing to 40
      mg/d after 2 wk. Eleven subjects completed 8 wk treatment and were included in
      the data analysis. Based on the Clinician-Administered Post-traumatic Stress
      Disorder Scale (CAPS-2), there was significant reduction in all core PTSD
      symptoms (re-experiencing, hyperarousal, and avoidance) by week 8. Nine of the 11
      completers were classified as 'responders' on Clinical Global Impression
      Improvement scores. Secondary measures of depression (Montgomery-Asberg
      Depression Rating Scale) and anxiety (Hamilton Anxiety Scale) also improved
      significantly by week 8. Citalopram was tolerated well, and there were no
      dropouts due to adverse effects. Data from this preliminary open trial suggests
      that citalopram, an SSRI, may be effective for reducing the key symptoms of PTSD,
      however, these findings need confirmation in double-blind, placebo-controlled
      trials.

PMID- 11343591
TI  - Thyroid hormone treatment of primary unipolar depression: a review.
AB  - A substantial number of depressed patients will fail to respond to standard
      antidepressant therapy. Thyroid hormones, particularly T3, may be particularly
      useful in enhancing response to antidepressants. This review focuses on the use
      of T3 augmentation in unipolar major depression. The study clearly suggests that
      approximately half of patients will respond to T3 augmentation of
      antidepressants. There are several limitations to the literature including the
      fact that most studies have used T3 in tricyclic rather than SSRI failure and
      most are of relatively short duration, up to 3 wk. Further studies are required
      of T3 efficacy with newer classes of antidepressants, optimal dose of T3 to be
      used and the duration of T3 augmentation, particularly if the acute trial is
      successful.

PMID- 11343592
TI  - Thyroxine and the treatment of affective disorders: an overview of the results of
      basic and clinical research.
AB  - Eight open clinical trials conducted by 7 different study groups and including 78
      patients have all demonstrated that augmentation with supraphysiological doses of
      thyroxine (T4) has antidepressant and prophylactic effects in roughly 50% of
      patients completely resistant to all other antidepressant and prophylactic
      therapies. Beneficial effects have been observed in unipolar and bipolar (rapid
      cycling and non-rapid-cycling) patients, but only when an antidepressant or
      prophylactic drug was administered concomitantly. Double-blind studies are now
      needed in order to confirm these results. It has also consistently been shown
      that high serum concentrations of T4 predict favourable response to
      antidepressant treatment and that the serum levels of T4 decrease in responders
      to these treatments, but not in non-responders. As thyroid hormone function in
      the CNS depends almost entirely on the uptake of T4 and its intracellular
      deiodination to the active compound T3, the hypothesis was investigated that the
      falls in serum levels of T4 seen during antidepressant treatment are due to
      enhanced conversion of T4 to T3 in the CNS. However, the results of several
      animal studies revealed that, while a number of different antidepressants do in
      fact each have specific effects on thyroid hormone metabolism in the CNS, no
      consistent enhancement of T3 concentrations has been demonstrated in homogenates
      of any relevant brain region. Recent studies measuring T3 in subcellular
      fractions have reported a selective increase in T3 levels in the mitochondria of
      the amygdala following various antidepressant treatments. The relevance of this
      finding must be clarified in further studies. However, in humans serum levels of
      T4 also decline after non-antidepressant treatments (for example, neuroleptics,
      anticonvulsants or benzodiazepines), and T3 concentrations in the rat brain are
      elevated by many other kinds of non- antidepressant treatment (e.g. stress). The
      function of T3 appears to be a rather general enhancement of all kinds of
      neuronal activity. Thus, it would seem unlikely that effects on thyroid hormone
      function are the decisive and specific step involved in the mechanism of action
      of antidepressant treatments. Rather, the function of T3 is altered as a
      secondary response to other primary effects of antidepressant treatments and also
      other psychopharmacological therapies.

PMID- 11343593
TI  - Mental improvement after replacement therapy with thyroxine plus
      triiodothyronine: relationship to cause of hypothyroidism.
AB  - We treated 26 hypothyroid women - 11 with autoimmune thyroiditis and 15 who had
      been treated for thyroid cancer - with their usual dose of thyroxine (T4) or with
      a regimen in which 50 &mgr;g of T4 had been replaced by 12.5 &mgr;g of
      triiodothyronine (T3). Patients were first randomly assigned to one regimen for 5
      wk and then to a second regimen for an additional 5 wk. The substitution of T3
      for a portion of T4 caused expected changes in concentrations of thyroid hormones
      and thyroid-stimulating hormone (TSH). After combined hormone treatment there
      were clear improvements in both cognition and mood, the latter changes being
      greater. The patients who had been treated for thyroid cancer showed more mental
      improvement than the women with autoimmune thyroiditis, perhaps because they were
      more dependent on exogenous hormone. Some mood improvements correlated positively
      with changes in TSH while others correlated negatively with changes in free T4.

PMID- 11343594
TI  - Minimizing the cognitive effects of lithium therapy and electroconvulsive therapy
      using thyroid hormone.
AB  - Although electroconvulsive therapy (ECT) and lithium are effective treatments for
      mood disorders, they are both associated with cognitive side-effects that reduce
      patient compliance and satisfaction. Because both ECT and lithium have
      significant impact on the hypothalamic-pituitary-thyroid (HPT) axis, at least
      some of these side-effects may be associated with alterations in HPT activity.
      There is evidence that cognitive deficits in patients with bipolar disorder
      taking lithium are related to diminished thyroid status, but not to serum lithium
      level. A preliminary study showed that adjunctive use of thyroid hormone
      significantly improves cognitive functioning in patients taking lithium. An
      animal study and two double-blind, placebo-controlled clinical studies examining
      the adjunctive use of thyroid hormone (T3) and ECT have confirmed that T3
      significantly protects against ECT-related memory impairment compared to placebo.
      Taken as a whole, this research suggests that adjunctive use of thyroid hormone
      has the potential to reduce cognitive side-effects of these important psychiatric
      treatments.

PMID- 11343595
TI  - Pharmacological mechanisms of T3 augmentation of antidepressant action.
AB  - Pharmacological mechanisms which have been proposed to account for the
      potentiating effect of T3 on antidepressant action include actions via nuclear
      receptors on gene expression, effects on membrane-bound receptors, and actions at
      the second-messenger level. Interactions of T3 with mechanisms involved in
      noradrenergic and serotonergic neurotransmission are of particular interest in
      that these systems have been implicated in the neurobiology of depression and in
      the actions of antidepressant drugs. Several examples of such interactions are
      discussed.

PMID- 11343596
TI  - Reboxetine in a neuroendocrine challenge paradigm: evidence for high cortisol
      responses in healthy volunteers scoring high on subclinical depression.
AB  - This paper investigates if the highly selective norepinephrine reuptake inhibitor
      reboxetine leads to a dose-dependent cortisol release and if this response
      depends on personality dimensions related to clinical depression in healthy
      volunteers. Twenty-four male subjects received placebo, 2 mg, or 4 mg reboxetine
      in a balanced, randomized cross-over study. Cortisol was measured in saliva at
      six different time-points according to the kinetics of the drug. Furthermore,
      several measurements of cardiovascular parameters, emotional states, and possible
      side-effects were obtained. Subjects were divided into two groups scoring above
      or below the median of a depressiveness questionnaire scale [n = 11, low (D-); n
      = 13, high (D+)]. Results clearly demonstrated, that reboxetine stimulates
      cortisol release. Whereas blood pressure was not affected, heart rate increased
      after 2 and 4 mg but not dose dependently. Subjects reported more non-specific
      arousal while the dimensions of tiredness-wakefulness and positive-negative
      emotional states were not affected by the drug. Somatic complaints were low and
      only non-specific complaints were statistically elevated but of negligible
      amount. Subjects classified as D+ can be characterized as high responders to the
      drug. This is especially true not only for cortisol increases but also for
      changes in heart rate and some ratings on physical complaints. Hot flushes,
      sweating and a throbbing sensation in blood vessels in the head were observed in
      D+ but only with the 4 mg dose. The results clearly demonstrate that reboxetine
      stimulates cortisol release and heart rate and that this is particularly
      pronounced in subjects scoring high on depression-related personality dimensions.
      Reboxetine, therefore, is a promising tool for investigating neuroendocrine
      response to noradrenergic challenge tests. The question whether increased
      responses in D+ are due to an up-regulation of receptor sensitivity as a
      consequence of low norepinephrine supply is discussed.

PMID- 11343597
TI  - A PET study of
AB  - Several radiolabelled cocaine analogues have been proposed for brain imaging of
      the dopamine transporter in research on neuropsychiatric disorders and drug
      abuse. In a recent positron emission tomography (PET) study we labelled the
      cocaine analogue beta-CIT-FE with carbon-11 and demonstrated high specific
      binding in the monkey striatum. In the present study, the selectivity of
      [11C]beta-CIT-FE binding in the primate brain was examined by pretreatment
      experiments with reference ligands for the dopamine, serotonin and norepinephrine
      transporter. In three healthy human subjects the regional binding of [11C]beta
      CIT-FE was analysed using equilibrium and kinetic analyses. A Scatchard analysis
      showed that [11C]beta-CIT-FE bound in a saturable manner yielded a density value
      of the same order as that reported in vitro. The pharmacological characterization
      indicated that a high degree of [11C]-CIT-FE binding in the primate striatum
      represents the dopamine transporter. In human subjects the radioligand provided
      high brain uptake and reached peak equilibrium within 1 hour after i.v.
      injection. Different quantitative approaches gave similar values for the binding
      potential. The results support the view that [11C]beta-CIT-FE is a suitable
      radioligand for clinical studies of the dopamine transporter. In particular for
      studies requiring short data acquisition or repeated PET measurements on the same
      day.

PMID- 11343598
TI  - Tryptophan hydroxylase gene 218A/C polymorphism is not associated with depressed
      suicide.
AB  - Abnormalities in functioning of the central serotonergic system are believed to
      be involved in the pathogenesis of depressive illness and suicidal behaviour.
      Recently, polymorphism in the tryptophan hydroxylase (TPH) gene has been studied
      for association with aggression, anger-related traits and suicidal behaviour, but
      the results are inconclusive. The present investigation was to determine whether
      there are differences in genotype and allele distribution of the TPH gene 218A/C
      polymorphism in post-mortem brain samples from 35 depressed suicide victims and
      84 control subjects of the same ethnic background. A functional polymorphism in
      the promoter region of 5-HT transporter gene was also re-examined in this
      increased sample size. No significant difference in TPH gene 218A/C polymorphism
      between controls and depressed suicide victims was detected. This may suggest
      that the TPH gene has no significant effect on suicidality in depressed subjects.
      In a previous study on a smaller sample we found the frequency of the long allele
      of 5-HT transporter gene to be higher in depressed suicide victims. In this
      increased sample size, both the genotype and alleles of the 5-HT transporter gene
      were significantly associated with completed suicide. The frequency of the L/L
      genotype in depressed suicide victims was almost double of that found in control
      group (48.6 vs. 26.2%). The odds ratio for the L allele associated with depressed
      suicide was 2.1 (95% CI, 1.2-3.7). The relatively small sample size does not
      exclude the possibility of false-positive results and the finding needs
      replication.

PMID- 11343599
TI  - Two-lever drug-drug discrimination with the 5-HT1 receptor agonists flesinoxan
      and eltoprazine.
AB  - Previous drug discrimination studies with the 5-HT1 receptor agonists flesinoxan
      and eltoprazine showed a clear 5-HT1A receptor-mediated effect for flesinoxan and
      the involvement of both 5-HT1A and 5-HT1B receptors in eltoprazine. However,
      there was no clear antagonism of eltoprazine's cue, possibly due to the compound
      nature of the eltoprazine stimulus. In the present experiments, in order to
      create a specific 5-HT1A vs. 5-HT1B receptor-mediated discrimination, rats were
      trained to discriminate between flesinoxan and eltoprazine. All rats learned the
      discrimination readily (mean = 41.3 sessions to criterion). With training doses
      of 1.0 mg/kg, p.o. flesinoxan and 1.5 mg/kg, p.o. eltoprazine, saline
      administration resulted in 50% of the responses made on both levers. Substitution
      tests showed that the flesinoxan stimulus was mediated by the 5- HT1A receptor (8
      OH-DPAT, buspirone) and the eltoprazine stimulus probably mediated by the 5-HT1B
      receptor (anpirtoline, TFMPP, RU-24969). The selective 5-HT1A receptor antagonist
      WAY-100635 antagonized the flesinoxan cue, and the discriminative stimulus of
      eltoprazine could be completely antagonized with the 5-HT1B/1D receptor
      antagonist GR-127935. When the training doses of both flesinoxan and eltoprazine
      were administered concurrently, complete substitution for eltoprazine was
      obtained. We conclude that rats can learn to discriminate between two
      serotonergic drugs with overlapping stimulus properties and that the flesinoxan
      stimulus is mediated by 5-HT1A receptors and the eltoprazine stimulus, under
      these particular training conditions, by 5-HT1B receptors.

PMID- 11343600
TI  - Reduction of platelet serotonin content in depressed patients treated with either
      paroxetine or desipramine.
AB  - Drugs thought to be selective inhibitors of either the uptake of serotonin (5-HT)
      or norepinephrine (NE) are known to be effective antidepressants. In general, a
      relative selectivity for NE vs. 5-HT uptake inhibition greater than 50-fold in
      vitro is thought to be sufficient to maintain such selectivity in vivo. To
      explore this issue, we carried out a study in which depressed patients were
      treated with either the selective serotonin reuptake inhibitor (SSRI) paroxetine
      or the selective norepinephrine reuptake inhibitor (SNRI) desipramine. Patients
      were treated with either drug or placebo for 6 wk. Drug levels in plasma and
      platelet 5-HT content were measured 12 times during the treatment period using
      HPLC procedures. Both drug treatments caused a significant reduction of platelet
      5-HT content. Paroxetine reduced platelet 5-HT content to approx. 1% of
      pretreatment levels (n = 3). The inhibition of 5-HT uptake by paroxetine appeared
      to be immediate and complete. Desipramine reduced platelet 5-HT content to 38.7+/
      6.2 % of pretreatment levels (n = 5) at a mean plasma level of 195 ng/ml. The
      percent reduction of platelet 5-HT content after 6 wk of drug treatment was
      proportional to the steady state plasma level of desipramine. The IC50 value of
      desipramine to reduce platelet 5-HT was 135 ng/ml. These results demonstrate that
      therapeutic concentrations of the SNRI desipramine as well as the SSRI paroxetine
      inhibited serotonin uptake in platelets of depressed patients. If such effects
      occur in the brain, desipramine might have some component of its therapeutic
      effects due to actions on the uptake of 5-HT.

PMID- 11343601
TI  - Cluster analysis of clinical data to identify subtypes within a study population
      following treatment with a new pentapeptide antidepressant.
AB  - Cluster analysis was used to evaluate the data from a placebo-controlled, double
      blind clinical trial with a new pentapeptide antidepressant (INN 00835) in major
      depression. The objective of this paper is to examine the effect of separating
      the study population into homogeneous subgroups (clusters) with relatively
      similar response to treatment within subgroups, and significantly different
      response between subgroups. The list of variables for cluster analysis was
      selected only from the efficacy parameters investigated in the study. Three to
      six clusters were modelled to obtain the optimal number of clusters, based on a
      proportional contribution of subjects per cluster, and the maximum statistical
      difference between clusters. After separation, the variability of response among
      drug-treated subjects by cluster was attributed to plasma drug concentration.
      Platelet serotonin uptake, which is a putative biochemical marker of effective
      treatment of depression, also reproduced the same effect of separation as the
      initially established cluster variables.

PMID- 11343602
TI  - N-Methyl-D-aspartate (NMDA) receptor-based treatment approaches in schizophrenia:
      the first decade.
AB  - The study of excitatory amino acids (EAA) [e.g. glutamate (Glu), aspartate] as
      neurotransmitters has resulted in many new and fundamental concepts in
      neuroscience. Much of this progress centres upon the role of N-methyl-D-aspartate
      (NMDA) subtype of Glu receptors in central nervous system synaptic transmission
      and plasticity. A leading hypothesis suggests that deficits in NMDA receptor
      mediated neurotransmission may be central to the pathophysiology of
      schizophrenia. The conceptual foundation of this hypothesis derives from the
      clinical effects of NMDA receptor antagonists, such as phencyclidine (PCP) and
      ketamine and from post-mortem findings in brain samples of schizophrenia
      patients. Consequently, at present there is an intense search for pharmacological
      strategies capable of facilitating NMDA receptor function in this illness. During
      the last decade, a first generation of small clinical studies has focused on
      assessing the therapeutic potential of glycine-(Gly) site agonists of the NMDA
      receptor, such as Gly, D-serine and D-cycloserine. The results of these studies
      indicate that this type of compound may reduce negative symptoms and executive
      cognitive deficits in schizophrenia patients. Furthermore, preliminary findings
      suggest that patients having low serum Gly levels may represent the population of
      choice for treatment with Gly-site agonists. Additional potential schizophrenia
      treatments that may affect mainly NMDA receptor neurotransmission are : (i) other
      full and partial Gly-site agonists - in course of development for clinical use,
      and (ii) Gly transport antagonists that can inhibit Gly reuptake from neuronal
      synapses. Moreover, the antipsychotic action of some typical and atypical
      neuroleptics may be mediated by their agonistic activity at the strychnine
      insensitive NMDA receptor-associated Gly site. After decades of relative neglect,
      the role of glutamatergic neurotransmission in the pathophysiology and
      therapeutics of schizophrenia is presently in process of conceptualization. In
      this context, it is likely that the development of NMDA receptor-based approaches
      for the treatment of this illness will continue. This trend is already supported
      by available clinical findings with Gly-site agonists and may herald an
      important, innovative development in the pharmacological treatment of
      neuropsychiatric syndromes.

PMID- 11343603
TI  - Transcranial magnetic stimulation: applications in basic neuroscience and
      neuropsychopharmacology.
AB  - Introduced 15 years ago, transcranial magnetic stimulation (TMS) is a non
      invasive means of stimulating the cortex that has proved to be a unique tool for
      probing brain-behaviour relationships. While a therapeutic role for TMS in
      neuropsychiatry is uncertain, the utility of TMS in studying brain function has
      been demonstrated in diverse neuroscience applications. We review studies in
      animals on the mechanisms of action of TMS, and present a summary of the
      applications of TMS in basic neuroscience. TMS is still a relatively young
      technique, and unanswered questions remain regarding its acute and chronic impact
      on neural excitability and various aspects of brain function. Nonetheless, recent
      work with TMS has demonstrated its unique role in complementing other tools for
      studying brain function. As a brain intervention tool, TMS holds the promise of
      moving beyond correlative studies to help define the functional role of cortical
      regions in selected cognitive and affective processes.

PMID- 11343604
TI  - Excessive yawning and SSRI therapy.
AB  - As we become more experienced with the long-term use of selective serotonin
      reuptake inhibitors (SSRIs), more subtle side-effects may become evident.
      Clinicians may be aware of yawning as a side-effect of antidepressant therapy,
      however sparse literature exists on the topic. We present two cases in which
      excessive daytime yawning was associated with SSRI treatment.

PMID- 11343605
TI  - Tryptophan depletion selectively reduces CSF 5-HT metabolites in healthy young
      men: results from single lumbar puncture sampling technique.
AB  - Plasma tryptophan (Trp) depletion is a commonly used tool for determining the
      role of brain serotonin (5-HT) function in a variety of psychiatric disorders.
      This study measured the cerebrospinal fluid (CSF) monoamine metabolite response
      to Trp depletion and control testing in five healthy subjects utilizing a single
      lumbar puncture. Testing was done in a placebo-controlled, double-blind,
      randomized, cross-over design. Plasma-free and total Trp levels and behavioural
      ratings were obtained prior to and 5 h after ingestion of each amino-acid drink.
      CSF was obtained by performing a standard lumbar puncture 7 h after ingestion of
      the drink. Compared to control testing, Trp depletion caused a significant
      decrease of CSF 5-hydroxyindoleacetic acid (5-HIAA) (p = 0.03), but not of
      homovanillic acid or 3-methoxy-4-hydroxy-phenylglycol. Behavioural ratings were
      minimally affected in all subjects. This confirms that plasma Trp depletion
      reduces central nervous system measures of 5-HT function and suggests that the
      single lumbar puncture technique may be sufficient to detect the extent of CSF 5
      HIAA changes during Trp depletion studies.

PMID- 11343606
TI  - The Schedule for the Assessment of Drug-Induced Movement Disorders (SADIMoD):
      test-retest reliability and concurrent validity.
AB  - The SADIMoD is a newly developed instrument, consisting of a compilation of
      rating scales, to measure the severity of drug-induced movement disorders:
      dystonia, dyskinesia, Parkinsonism, akathisia, ataxia, and several types of
      tremors. The test-retest reliability of this scale and the concurrent validity
      with the Abnormal Involuntary Movement Scale (AIMS), the Simpson-Angus Scale
      (SEE) and the Barnes Akathisia Scale (BAS) was assessed in 31 patients [20
      male/11 female; 57.1+/-16.5 yr (mean+/-S.D.)] with a variety of movement
      disorders by six teams of investigators. The teams were trained by means of a
      standard package of instruction material to such an extent that a single member
      of the team could represent the entire team. Each patient was rated according to
      the AIMS, SEE and BAS and recorded on videotape according to the SADIMoD
      Schedule. These video-recordings were scored twice; first, in consensus by the
      entire team and secondly [110.3+/-58.0 d (mean+/-S.D.) later] by a single
      representative of that team. One team underwent a major change between scoring
      and was excluded from this analysis. Despite these difficult circumstances, these
      first and second ratings correlated to a highly significant degree with
      Spearman's correlation coefficients of 0.57 to 0.88 (median 0.69). The
      homogeneity of the applied scales was good (Cronbach's a = 0.75-0.94). Convergent
      validity was found between the SADIMoD dyskinesia and (to a lesser extent)
      dystonia scales and the AIMS as well as between the akathisia sub-scales and the
      BAS, with divergent validity with the other sub-scales. The SEE discriminated
      less well between the Parkinsonism sub-scale and the other sub-scales.

PMID- 11343607
TI  - Repetitive transcranial magnetic stimulation to right prefrontal cortex does not
      modulate the psychostimulant effects of amphetamine.
AB  - Preliminary evidence indicates lateralized efficacy of repetitive transcranial
      magnetic stimulation (rTMS) in the treatment of mood disorders. Right-sided
      prefrontal cortex (PFC) stimulation has been reported to treat symptoms of mania.
      The acute effect of amphetamine serves as a model of mania in healthy
      individuals, hence rTMS to right PFC was hypothesized to attenuate the
      psychostimulant action of amphetamine in healthy volunteers. Eighteen subjects
      received rTMS to right PFC or right parietal cortex (PAR), or sham stimulation,
      in a randomized between-subjects design. Following rTMS subjects received i.v.
      amphetamine (0.15 mg/kg). Intravenous amphetamine induced robust subjective
      (visual analogue scales) and objective (blood pressure, sustained attention)
      effects, but the extent of the effects was not modulated by right PFC
      stimulation. Though this dose cannot refute the efficacy of rTMS in treating
      mania, it indicates that any therapeutic mechanism of action is unlikely to be
      through modulation of dopamine function.

PMID- 11343608
TI  - Involvement of the opioid system in the development and expression of
      sensitization to the locomotor-activating effect of ethanol.
AB  - Previous studies have shown that pretreatment with naloxone (Nlx), an opiate
      antagonist, attenuates the stimulating effect of ethanol. The purpose of the
      present study was to determine the influence of Nlx on the development and
      expression of the sensitization to ethanol. Initially, effects of different doses
      of Nlx on the response to a low dose of ethanol (2.0 g/kg) were assessed. Nlx
      (1.0 and 3.0 mg/kg i.p.) decreased the stimulating effect of ethanol. Groups of
      mice were treated with saline or Nlx (1.0 mg/kg i.p.) plus saline or ethanol (2.0
      g/kg i.p.) during 21 d. On day 25 of treatment all animals received an ethanol
      challenge (2.0 g/kg i.p.). It significantly increased the locomotor activity of
      mice that had received chronic ethanol (2.0 g/kg) once daily as compared to those
      that had received saline. Chronic administration of Nlx (1.0 mg/kg i.p.), during
      the same period of time, did not change the locomotor activity of the mice.
      However, the group concomitantly treated with Nlx+ethanol did not develop
      sensitization to the locomotor-activating effect of ethanol. Another experiment
      was carried out to determine the effects of Nlx on the expression of
      sensitization to ethanol. Acute pretreatment with Nlx did not change the response
      of the mice that had developed sensitization to ethanol. These data show Nlx's
      prevention of the development of ethanol-induced sensitization but not of its
      expression, suggesting an important role of the opioid neurotransmitter systems
      modulating the development of sensitization to the locomotor-activating effect of
      ethanol.

PMID- 11343609
TI  - Chromium treatment of depression.
AB  - Eight patients with refractory mood disorders received chromium supplements and
      described dramatic improvements in their symptoms and functioning. In several
      instances, single-blind trials confirmed specificity of response to chromium.
      Side-effects were rare and mild, and most commonly included enhanced dreaming and
      mild psychomotor activation. To our knowledge, this is the first case series
      describing the response to chromium monotherapy. The putative antidepressant
      effects of chromium could be accounted for by enhancement of insulin utilization
      and related increases in tryptophan availability in the central nervous system,
      and/or by chromium's effects on norepinephrine release.

PMID- 11343610
TI  - Serotonin-stimulated calcium release is decreased in platelets from high
      impulsivity patients.
AB  - Impulsivity is a significant factor in many behavioural disorders. Previous
      studies have shown that dysfunction of serotonin (5-HT) pathways are correlated
      with impulsivity, but an underlying causative mechanism has not as yet been
      identified. The present study examined 5-HT-stimulated Ca2+ release from
      platelets from 33 patients exhibiting high impulsivity according to the Barratt
      Impulsivity Scale and from 26 healthy volunteers. 5-HT-stimulated Ca2+ release
      was significantly decreased in patients as compared to controls. These results
      indicate that impulsivity is linked to alterations in the 5-HT second-messenger
      cascade and suggest that further efforts should be made to understand the
      specific abnormalities in this complex pathway. This understanding may lead to
      the development of therapeutic strategies specific for regulation of 5-HT
      stimulated Ca2+ release, providing more effective treatment for impulsive
      behavioural disorders.

PMID- 11343611
TI  - Novel 5'-regulatory region polymorphisms of the 5-HT2C receptor gene: association
      study with panic disorder.
AB  - Candidate genes for association studies in panic disorder are often selected on
      the basis of molecular mechanisms of drugs utilized in challenge tests such as m
      chlorophenylpiperazine (mCPP), a non-selective 5-HT2C receptor agonist. Two
      novel, adjacent polymorphisms [(GT)12-18 and (CT)4-5] in the 5'-regulatory region
      of the X-chromosomal 5-HT2C receptor gene have recently been reported. We
      determined the allele frequency of long vs. short polymorphism haplotypes in a
      German and an Italian sample (combined n = 211) of panic disorder patients (DSM
      III-R) and compared it with allele frequencies in two ethnically matched control
      samples (combined n = 226). In the German sample, a comparison of female
      genotypes containing the short haplotype vs. female genotypes containing only
      long haplotypes showed a significant difference (p = 0.01, ?2 analysis). In the
      Italian sample, however, this observation could not be replicated (p = 0.54, ?2
      analysis). This argues against a major role for these promoter-associated 5-HT2C
      receptor gene length polymorphisms in the aetiopathogenesis of panic disorder.

PMID- 11343612
TI  - Obsessive-compulsive disorder and the promoter region polymorphism (5-HTTLPR) in
      the serotonin transporter gene (SLC6A4): a negative association study in the
      Afrikaner population.
AB  - A polymorphism (5-HTTLPR) in the promoter region of the serotonin transporter
      gene (SLC6A4) has been reported to have functional significance and to be
      associated with obsessive-compulsive disorder (OCD). However, other studies have
      generated confounding results. A study was undertaken to re-evaluate this
      association in subjects drawn from the relatively genetically homogeneous
      Afrikaner population of South Africa. Fifty-four OCD patients of Afrikaner
      descent and 82 ethnically matched control individuals were phenotyped and
      genotyped. No significant association was found between the distribution of the 5
      HTTLPR genotypes at the SLC6A4 locus and OCD. A similar result (p = 0.108) was
      generated when a meta-analysis of the 5-HTTLPR polymorphism, combining the
      current study with a previously reported Caucasian group, was performed; the meta
      study comprised 129 OCD patients and 479 control individuals. However, both
      studies lacked power. Therefore, evidence that variation in SLC6A4 plays a
      significant role in the development of OCD in the population groups studied is
      inconclusive. Future association studies in Caucasian populations may extend the
      power of such meta-analyses and assist in delineating the role of SLC6A4 in OCD.

PMID- 11343613
TI  - Role of serotonergic 5-HT2A receptors in the psychotomimetic actions of
      phencyclidine.
AB  - The psychotomimetic phencyclidine (PCP) alters various behavioural responses
      involving the serotonergic system including potentiating the discriminative
      stimulus effects of the phenethylamine hallucinogen, 2,5-dimethoxy-4
      methylamphetamine (DOM). The present study was undertaken to test the hypothesis
      that PCP directly interacts with the 5-HT2A receptor. PC12 cells, a neuronal cell
      line, were stably transfected with the cDNA encoding the rat 5-HT2A receptor
      (PC12-5-HT2A). In these cells PCP and the related compounds, ketamine and
      dizocilpine, did not increase [3H]inositol phosphate generation nor did they
      alter 5-HT-stimulated phosphoinositide hydrolysis. These compounds also did not
      display appreciable affinity for the 5-HT2A receptor labelled with
      [3H]ketanserin. The present study indicates that the behavioural responses to
      PCP, ketamine and dizocilpine do not involve a direct interaction of these
      compounds with the 5-HT2A receptor.

PMID- 11343614
TI  - The new generation of antipsychotic drugs: how atypical are they?
AB  - The cardinal feature of traditional neuroleptic drugs is extrapyramidal symptoms
      (EPS), such as parkinsonism, akathisia, and dystonia. Irrespective of the
      autonomic nervous system side-effect profile of a specific neuroleptic, the
      entire class produces EPS. Therefore, EPS and antipsychotic activity were once
      thought to be inextricably linked. However, with the discovery of clozapine, this
      concept was no longer defensible. Clozapine produced antipsychotic actions
      without associated EPS or increases in serum prolactin levels, and the term
      'atypical' was coined to differentiate its actions from those of the traditional
      agents. Later, the definition of atypical was expanded to encompass clozapine's
      unique clinical spectrum of activity, including its effectiveness in treating
      some patients unresponsive to traditional neuroleptics. Clozapine thus became the
      archetype for a new generation of antipsychotic drugs, which now includes
      quetiapine, olanzapine, risperidone, sertindole, ziprasidone, zotepine and
      amisulpride. This paper will review the pharmacological actions that contribute
      to the unique features of clozapine, focusing on receptor profile and activity in
      animal models used for evaluations of antipsychotic activity and EPS.
      Similarities and differences amongst the new agents will also be discussed.
      Although conclusions regarding atypicality require controlled clinical trials in
      addition to preclinical and animal models, it is apparent from this review that
      not all agents match the profile of clozapine.

PMID- 11343615
TI  - Pioneers in Psychopharmacology II.
AB  - In 1998, the first Pioneers in Psychopharmacology Awards were presented at the
      XXIst CINP Meeting in Glasgow to Pierre Deniker, Joel Elkes and Heinz Lehmann.
      These three individuals had distinguished themselves and Psychopharmacology not
      only by the quality of their work but also by their ability to persuade others of
      the importance of the new field that was opening up (Healy, 1998). At the XXIInd
      CINP Meeting in Brussels in July 2000, Paul Janssen, Mogens Schou and Alec Coppen
      became the second group to receive such awards for distinguished achievement.

PMID- 11343617
TI  - IJNP Calendar.

PMID- 11343618
TI  - Introduction.
AB  - Alzheimer's disease (AD) is the commonest form of dementia in developed
      countries, accounting for approx. 50-60% of the overall cases of dementia among
      persons over 65 years of age. Furthermore, because of the world's ageing
      population, and without an effective prevention or treatment, a sharp rise in the
      prevalence of dementia with age is predicted. AD itself is a progressive and
      irreversible neurodegenerative disorder associated with three main clinical
      features in the domains of declines in cognitive function (neuropsychologic) and
      activities of daily living, together with neuropsychiatric symptoms (including
      behavioural disturbances). These expressions of the pathology of AD impact
      tremendously not only in terms of the patient, but also the carer and society in
      general. Considering the high frequency of AD in the aged population, the rapid
      growth of the elderly population, and the heavy impact in terms of disability, AD
      has become a major problem for healthcare systems, public health planning and
      society as a whole. The scale of this problem presents a huge economic burden, in
      terms of both direct (healthcare system resources) and indirect (unpaid carer
      services) costs. Thus, the last two decades have witnessed an enormous research
      effort directed towards discovering the cause of AD with the ultimate hope of
      developing safe and effective pharmacological treatments.

PMID- 11343619
TI  - The cholinergic deficit in Alzheimer's disease: impact on cognition, behaviour
      and function.
AB  - Although the neurodegeneration occurring in Alzheimer's disease (AD) affects
      multiple neurotransmitters, the cholinergic system has received the greatest
      attention. Acetylcholine (ACh) is fundamental to mnemonic function, assisting in
      the septal hippocampal pathway and facilitating cortical activation. One of the
      earliest pathological events in AD is the degeneration of ACh-synthesizing
      neurons in the subcortical nuclei of the human basal forebrain. Indeed, the loss
      of cholinergic function in AD is correlated with the density of histopathological
      markers of AD, the severity of cognitive dysfunction and disease duration.
      However, the precise mechanism by which the cholinergic system influences
      cognition, and behaviour, is unknown. Recent preliminary data from functional
      imaging and ligand-binding studies implicate a dynamic interaction between the
      nicotinic-muscarinic cholinergic receptor systems. The relatively preserved
      thalamic nicotinic system, compared with the dysfunctional cortical muscarinic
      system, may facilitate thalamocortical metabolic excitation in the failing AD
      brain. Thus, it is hypothesized that thalamic influence within frontal
      subcortical circuits is augmented in AD patients who demonstrate a marked
      improvement to cholinesterase inhibitor therapy. Understanding the cholinergic
      basis of the cognitive, functional and behavioural deficits in AD, and the
      differential treatment response to various agents, will ultimately improve
      patient care and neuropharmacological insights. This paper reviews the current
      understanding of the cholinergic influence in cognition, behaviour and, as a
      result, function in AD patients.

PMID- 11343620
TI  - Management of cognition and function: new results from the clinical trials
      programme of Aricept(R) (donepezil HCl).
AB  - Ideally, treatment for Alzheimer's disease (AD) should prevent or cure the
      disease. Unfortunately, these goals appear unobtainable in the foreseeable
      future. Nevertheless, symptomatic relief is a feasible treatment option for AD
      patients and is available currently in the form of cholinesterase inhibitors such
      as tacrine, donepezil, metrifonate and rivastigmine. Donepezil is a second
      generation, piperidine-class, selective and reversible acetylcholinesterase
      inhibitor. Four double-blind, placebo-controlled clinical trials of donepezil,
      involving over 1900 individuals with mild to moderate AD, have been published
      recently. In all trials, significant improvements in cognition were observed
      consistently for both therapeutic doses of donepezil (5 and 10 mg/d), relative to
      placebo. Similar donepezil-associated benefits were reported for global
      functioning. In addition, in one 24-wk, multinational clinical trial, patients
      receiving donepezil (10 mg/d) performed better than placebo-treated patients in
      their ability to perform complex daily functioning tasks. Donepezil was well
      tolerated in all trials, with approx. 79% of all donepezil-treated patients
      completing the studies compared with approx. 84% of placebo-treated patients. The
      most common adverse events associated with donepezil were generally cholinergic
      induced and gastrointestinal in nature (e.g. nausea, diarrhoea, and vomiting)
      which were generally mild, transient and tended to occur after the dose was
      increased to 10 mg/d from 5 mg/d after 1 wk only. Sleep disturbances also
      occurred as the clinical trials utilized a bedtime dosing regimen. There was no
      evidence of organ toxicity or clinically significant treatment-emergent
      laboratory test abnormalities. Thus, donepezil appears to be a beneficial
      symptomatic treatment for patients with mild to moderate AD.

PMID- 11343621
TI  - The role of cholinergic agents in the management of behavioural disturbances in
      Alzheimer's disease.
AB  - Alzheimer's disease (AD) is characterized by progressive cognitive deterioration,
      neuropsychological or behavioural disturbances, and eventual elementary
      neurological dysfunction. Changes in these domains lead to a reduced functional
      ability of the AD patient which results, inevitably, in an increasing dependency
      of the patient on their carer. Thus, a compromised quality of life for both the
      patient with AD and the carer ensues. The clinical deterioration in AD is
      produced by neurochemical deficits (involving cholinergic, noradrenergic and
      serotonergic systems) and histological changes (neuritic plaques, neurofibrillary
      tangles and neuronal death) in the brain. The abnormality in cholinergic
      neurotransmission, by contributing to both the cognitive impairment and possibly
      the behavioural disturbances of AD patients, has attracted particularly intense
      scientific attention. Evidence for the involvement of a cholinergic dimension to
      the behavioural changes of AD includes the following: the induction of AD-like
      behaviours in normal individuals by administration of anticholinergic drugs; the
      exaggeration of behavioural disturbances in AD patients by anticholinergic
      agents; the correlation of the distribution of cholinergic deficits of AD with
      regions that are relevant to the observed behaviours, i.e. the frontal and
      temporal regions; and the amelioration of behavioural disturbances in AD patients
      treated with cholinergic receptor agonists and cholinesterase inhibitors. This
      article reviews the increasing evidence that, in addition to their effects on the
      cognitive and functional domains of AD, cholinergic drugs may be considered
      psychotropic agents and are useful in the treatment of specific disorders with
      cholinergic deficits such as AD.

PMID- 11343622
TI  - The burden of Alzheimer's disease.
AB  - Alzheimer's disease (AD) imposes a severe burden upon patients and their carers.
      In particular, family carers of AD patients face extreme hardship and distress
      that represents a major but often hidden burden on healthcare systems. Carers
      often experience clinically significant alterations in physical and mental
      health, particularly depression. A number of individual features of the dementia
      syndrome that are known to be particularly burdensome to carers include the
      degree of cognitive impairment, amount of help required with activities of daily
      living, personality changes and the presence of psychiatric symptoms and
      behavioural disturbances. The neuropsychiatric features of AD patients can
      adversely impact the relationship between the patient and caregiver generating
      feelings of strain, burden and social isolation. Individual characteristics of
      the caregiver including personality, gender, degree of formal and informal
      support and physical and mental health, as well as attributional style ('coping
      style') and expressed emotion (critical or hostile attitudes), also dictate carer
      burden. As informal caregivers play such a crucial role in the care of AD
      patients, appropriate management strategies that incorporate interventions which
      address the specific burdens of the individual caregiver are essential. Reducing
      the burden of care can be achieved by the combination of a number of individual
      and general measures, including education, respite and emotion-focused
      interventions. These measures, accompanied by non-pharmacological strategies, are
      extremely important in the total care of the AD patient, with the emphasis on
      maintaining people in the community as long as possible.

PMID- 11343623
TI  - Corticosterone selectively attenuates 8-OH-DPAT-mediated hypothermia in mice.
AB  - The 5-HT1A agonist 8-OH-DPAT produces a hypothermia in mice mediated by
      somatodendritic 5-HT1A receptors, that is attenuated by antidepressants and
      corticosterone. The present study investigated if the effect of corticosterone is
      specific to the serotonergic system or a non-specific effect on thermoregulation.
      Administration of corticosterone for 3 d had no effect on dopaminergic
      (apomorphine) or adrenergic (clonidine) hypothermic challenges. However in
      addition to 8-OH-DPAT, nicotine-induced hypothermia was attenuated by
      corticosterone. Administration of the selective nicotinic antagonist mecamylamine
      had no effect on 8-OH-DPAT-induced hypothermia, although nicotine-induced
      hypothermia was attenuated by the selective 5-HT1A antagonist WAY-100635. This
      demonstrates a serotonergic-nicotinic interaction in the generation of
      hypothermia in mice and is consistent with corticosterone selectively attenuating
      somatodendritic 5-HT1A receptor function.

PMID- 11343624
TI  - Lack of interaction between flibanserin and antidepressants in inducing
      serotonergic syndrome in rats.
AB  - This study was aimed at evaluating the ability of flibanserin, a 5-HT1A receptor
      full agonist with antidepressant potential, to induce the 5-HT syndrome (flat
      body posture, hindlimb abduction and forepaw treading) in rats previously
      administered with clinically active antidepressants imipramine, fluoxetine or
      paroxetine. The 5-HT syndrome was observed for 50 min after intraperitoneal
      administration of flibanserin (0, 8 or 64 mg/kg) given 10 min after
      antidepressants (0 or 15 mg/kg). Flibanserin induced flat body posture and very
      slight hindlimb abduction only at 64 mg/kg. No dose of flibanserin elicited
      forepaw treading. Similar but milder symptoms were induced by antidepressants. No
      interaction between flibanserin and antidepressants was observed. A dose of 10
      mg/kg flibanserin did not change the flat body posture induced by 8 mg/kg (+/-)-8
      OH-DPAT but antagonized (+/-)-8-OH-DPAT-induced forepaw treading.

PMID- 11343625
TI  - QT interval variability in panic disorder patients after isoproterenol infusions.
AB  - Anxiety symptoms are associated with a marked increase in sudden cardiac death,
      suggesting an abnormality in the autonomic control of the heart. We examined the
      effects of sympathetic stimulation on QT interval variability in panic disorder
      patients by infusing the ss-adrenergic agonist isoproterenol in 6 panic disorder
      patients and 11 normal subjects. The ECG signal was analysed before the infusion
      and after 5 min after the infusion was started. The outcome measures were the QT
      variability normalized for mean QT interval (QTvm) and the QT variability index
      (QTvi), a measure of QT variability normalized by the concomitant heart rate
      variability. Patients with panic disorder had more variability in QT interval
      duration than normal controls and this variability was increased further by
      sympathetic stimulation with isoproterenol. The isoproterenol-associated increase
      in QT interval occurred in controls in the absence of significant anxiety.
      However, on one of two measures, the increase in QT interval variability was
      greater in patients with panic disorder, suggesting a greater sensitivity to
      isoproterenol or to isoproterenol-induced anxiety.

PMID- 11343626
TI  - Basal limbic system alteration in major depression: a hypothesis supported by
      transcranial sonography and MRI findings.
AB  - The pathogenesis of major depression (MD) remains unclear despite intensive
      research in the last decades which brought up a multitude of findings
      illustrating the complexity of this disorder. In this paper we will summarize the
      evidence pointing towards a structural alteration of the basal limbic system in
      MD and depression in Parkinson's disease (PD). Transcranial ultrasound and MRI
      studies in both depressive syndromes revealed altered signal intensity of the
      brainstem midline comprising fibre tracts of the basal limbic system. The
      hypothesis of a structural disruption of the basal limbic system is supported by
      biochemical and histopathological findings. The similarity of findings in MD and
      depression in PD might reflect a relationship between MD and neurodegenerative
      disorders.

PMID- 11343627
TI  - Monoamine oxidases and tobacco smoking.
AB  - Although nicotine has been identified as the main ingredient in tobacco
      responsible for aspects of the tobacco dependence syndrome, not all of the
      psychopharmacological effects of smoking can be explained by nicotine alone.
      Accumulating preclinical and clinical evidence has demonstrated that smoking also
      leads to potent inhibition of both types (A and B) of monoamine oxidase (MAO).
      Smokers have 30-40 % lower MAOB and 20-30 % lower MAOA activity than non-smokers.
      Reduced MAO activity in smokers has been shown by direct measures (platelets,
      positron emission tomographic studies) or by indirect measures (concentration of
      monoamine catabolites in plasma or CSF). We examine the hypothesis that chronic
      habitual smoking can be better understood in the context of two pharmacological
      factors: nicotine and reduced MAO activity. We speculate that MAO inhibition by
      compounds found in either tobacco or tobacco smoke can potentiate nicotine's
      effects. Based on this concept, more effective anti-smoking drug strategies may
      be developed. As a practical consequence of tobacco smoke's MAO-inhibitory
      properties, comparative psychiatric research studies need to screen and control
      for tobacco use.

PMID- 11343628
TI  - Venlafaxine withdrawal syndrome not prevented by maprotiline, but resolved by
      sertraline.

PMID- 11343630
TI  - Mood stabilizers regulate cytoprotective and mRNA-binding proteins in the brain:
      long-term effects on cell survival and transcript stability.
AB  - Manic depressive illness (MDI) is a common, severe, chronic and often life
      threatening illness. Despite well-established genetic diatheses and extensive
      research, the biochemical abnormalities underlying the predisposition to, and the
      pathophysiology of, these disorders remain to be clearly established. Despite
      formidable obstacles in our attempts to understand the underlying neurobiology of
      this illness, there is currently considerable excitement about the progress that
      is being made using novel strategies to identify changes in gene expression that
      may have therapeutic relevance in the long-term treatment of MDI. In this paper,
      we describe our recent research endeavours utilizing newer technologies,
      including a concerted series of mRNA RT-PCR studies, which has led to the
      identification of novel, hitherto completely unexpected targets for the long-term
      actions of mood stabilizers - the major cytoprotective protein bcl-2, a human
      mRNA binding (and stabilizing) protein, AUH, and a Rho kinase. These results add
      to the growing body of data suggesting that mood stabilizers may bring about some
      of their long-term benefits by enhancing neuroplasticity and cellular resilience.
      These results are noteworthy since recent morphometric brain imaging and post
      mortem studies have demonstrated that MDI is associated with the atrophy and/or
      loss of neurons and glia. The development of novel treatments which more directly
      target molecules involved in critical CNS cell survival and cell death pathways
      have the potential to enhance neuroplasticity and cellular resilience, and
      thereby modulate the long-term course and trajectory of these devastating
      illnesses.

PMID- 11343631
TI  - Identification of mood stabilizer-regulated genes by differential-display PCR.
AB  - An increasing body of evidence demonstrates that lithium and valproate have a
      regulatory effect on signal transduction pathways. Alteration of signalling
      molecules triggers changes in gene expression which are thought to contribute to
      the therapeutic effects of these drugs on bipolar disorder. Differential-display
      PCR was used to identify genes in rat cerebral cortex that are regulated by
      chronic treatment with lithium and valproate. One novel lithium-regulated gene
      was identified and was characterized and studied further with 5'-RACE-PCR and
      library screening. We also found that valproate regulated the expression of the
      78-kDa glucose-regulated protein (GRP78). Chronic treatment with valproate has
      also been found to increase gene transcription, mRNA and protein levels of GRP78.
      These results suggest novel targets for lithium and valproate that may be
      relevant to their mechanism of action. The data further our understanding of the
      mechanism of the action of mood stabilizers, and help identify new targets for
      genetic studies and therapeutic strategies in bipolar disorder.

PMID- 11343632
TI  - Can 'differential display' methodologies make an impact on biological psychiatry?
AB  - The past decade has been marked by a dramatic increase in the availability of
      techniques to identify and clone genes that are differentially expressed in
      disease states and by drug treatments. The applications of such techniques to
      problems in biological psychiatry are manifold and the implications of
      discovering novel and/or known genes that are perturbed in neuropsychiatric
      disorders profound. While there are success stories, it is becoming ever more
      apparent that each of these techniques has its limitations, particularly when
      applied to the central nervous system. Given that these methods (e.g.
      differential display, RNA fingerprinting, suppression-subtractive hybridization,
      microarrays) are labour-intensive and potentially time-consuming, it is important
      to understand these limitations. For example, differential display is capable of
      detecting very small changes in the expression of mRNA species. Methods like
      suppression-subtractive hybridization are better suited to examine potential
      differences in rare transcripts, but only when their expression is changed
      substantially (currently ? 5-fold). Moreover, both the functional and
      morphological organization of the central nervous system present challenges that
      may not be encountered in other systems. In this overview, we will discuss the
      advantages and disadvantages of some of these approaches and their application to
      research in biological psychiatry.

PMID- 11343633
TI  - Emerging technologies for large-scale screening of human tissues and fluids in
      the study of severe psychiatric disease.
AB  - Neuropsychiatric diseases such as schizophrenia and bipolar disorder are major
      causes of morbidity throughout the world. Despite extensive searches, no single
      gene, RNA transcript, or protein has been found which can, on its own, account
      for these disorders. Recently, the availability of genomic tools such as cDNA
      microarrays, serial analysis of gene expression (SAGE) and large-scale sequencing
      of cDNA libraries has allowed researchers to assay biological samples for a large
      number of RNA transcripts. Similarly, proteomic tools allow for the quantitation
      of a large number of peptides and proteins. These methods include two-dimensional
      electrophoresis and surface-enhanced laser desorption/ionization (SELDI). We have
      initiated experiments which apply these techniques to the comparison of RNAs and
      proteins expressed in clinical samples obtained from individuals with psychiatric
      diseases and controls. These methods have the potential to identify pathways that
      are involved in the pathogenesis of complex psychiatric disorders. The
      characterization of these pathways may allow for the development of new methods
      for the diagnosis and treatment of schizophrenia, bipolar disorder, and other
      human psychiatric diseases.

PMID- 11343634
TI  - Proteomics in neuropsychiatric disorders.
AB  - Assessing human cerebrospinal fluid (CSF) provides a practical way to conduct
      longitudinal molecular analyses of changes during the course of neurological
      disease. Integrated and parallel analyses of neurotransmitters, neuropeptides and
      proteins in CSF may reveal better insights into complex interaction of numerous
      cell types in the central nervous system (CNS) at an unprecedented level of
      complexity and detail. Intricate molecular fingerprints of CSF proteins may
      pinpoint multiple underlying pathogenic mechanisms as well as an acute and a
      chronic CNS disease component. Some of these changes may be mapped to altered
      protein expression patterns in clinically relevant cell populations with a
      causative or diagnostic disease link. A CNS proteome database of primary human
      CNS tissues may avoid ambiguities of experimental models and accelerate pre- and
      clinical development of more specific diagnostic and prognostic disease markers
      and new selective therapeutics.

PMID- 11343635
TI  - When do epileptic seizures really begin?

PMID- 11343636
TI  - An end in sight to a long TRP.

PMID- 11343637
TI  - Rapid-fire synaptic vesicle exocytosis.

PMID- 11343638
TI  - Nematodes are smarter than you think.

PMID- 11343639
TI  - Sleeper's wake.

PMID- 11343640
TI  - Nogo domains and a Nogo receptor: implications for axon regeneration.

PMID- 11343641
TI  - Sensorineural deafness and pigmentation genes: melanocytes and the Mitf
      transcriptional network.

PMID- 11343642
TI  - Stem cells and pattern formation in the nervous system: the possible versus the
      actual.

PMID- 11343643
TI  - A novel technique that measures peptide secretion on a millisecond timescale
      reveals rapid changes in release.
AB  - Neuropeptides are ubiquitous transmitters that have been implicated in a wide
      variety of physiological and pathological conditions, and it is important to
      understand the processes that control their secretion. We have developed a
      technique that measures neuropeptide secretion with high temporal resolution.
      This method involves placing an electrophysiological "tag" in a neuropeptide
      prohormone. The tagged prohormone is subsequently expressed together with an
      ionotropic receptor that binds the tag. Because the neuropeptide of interest and
      the tag enter the same population of dense core granules, neuropeptide secretion
      gives rise to fast, synaptic-like currents. Using this method, we show that
      peptide secretion can be modulated on a millisecond time scale. This technique
      could be readily adapted to measure the secretion of any neuropeptide.

PMID- 11343644
TI  - Epileptic seizures may begin hours in advance of clinical onset: a report of five
      patients.
AB  - Mechanisms underlying seizure generation are traditionally thought to act over
      seconds to minutes before clinical seizure onset. We analyzed continuous 3- to 14
      day intracranial EEG recordings from five patients with mesial temporal lobe
      epilepsy obtained during evaluation for epilepsy surgery. We found localized
      quantitative EEG changes identifying prolonged bursts of complex epileptiform
      discharges that became more prevalent 7 hr before seizures and highly localized
      subclinical seizure-like activity that became more frequent 2 hr prior to seizure
      onset. Accumulated energy increased in the 50 min before seizure onset, compared
      to baseline. These observations, from a small number of patients, suggest that
      epileptic seizures may begin as a cascade of electrophysiological events that
      evolve over hours and that quantitative measures of preseizure electrical
      activity could possibly be used to predict seizures far in advance of clinical
      onset.

PMID- 11343645
TI  - Direct neural fate specification from embryonic stem cells: a primitive mammalian
      neural stem cell stage acquired through a default mechanism.
AB  - Little is known about how neural stem cells are formed initially during
      development. We investigated whether a default mechanism of neural specification
      could regulate acquisition of neural stem cell identity directly from embryonic
      stem (ES) cells. ES cells cultured in defined, low-density conditions readily
      acquire a neural identity. We characterize a novel primitive neural stem cell as
      a component of neural lineage specification that is negatively regulated by
      TGFbeta-related signaling. Primitive neural stem cells have distinct growth
      factor requirements, express neural precursor markers, generate neurons and glia
      in vitro, and have neural and non-neural lineage potential in vivo. These results
      are consistent with a default mechanism for neural fate specification and support
      a model whereby definitive neural stem cell formation is preceded by a primitive
      neural stem cell stage during neural lineage commitment.

PMID- 11343646
TI  - Hepatocyte growth factor/scatter factor is a motogen for interneurons migrating
      from the ventral to dorsal telencephalon.
AB  - Cortical interneurons arise from the proliferative zone of the ventral
      telencephalon, the ganglionic eminence, and migrate into the developing
      neocortex. The spatial patterns of migratory interneurons reflect the
      complementary expression of hepatocyte growth factor/scatter factor (HGF/SF) and
      its receptor, MET, in the forebrain. Scatter assays on forebrain explants
      demonstrate regionally specific motogenic activity due to HGF/SF. In addition,
      exogenous ligand disrupts normal cell migration. Mice lacking the urokinase-type
      plasminogen activator receptor (u-PAR), a key component of HGF/SF activation,
      exhibit deficient scatter activity in the forebrain, abnormal interneuron
      migration from the ganglionic eminence, and reduced interneurons in the frontal
      and parietal cortex. The data suggest that HGF/SF motogenic activity, which is
      essential for normal development of other organ systems, is a conserved mechanism
      that regulates trans-telencephalic migration of interneurons.

PMID- 11343647
TI  - Compact myelin dictates the differential targeting of two sodium channel isoforms
      in the same axon.
AB  - Voltage-dependent sodium channels are uniformly distributed along unmyelinated
      axons, but are highly concentrated at nodes of Ranvier in myelinated axons. Here,
      we show that this pattern is associated with differential localization of
      distinct sodium channel alpha subunits to the unmyelinated and myelinated zones
      of the same retinal ganglion cell axons. In adult axons, Na(v)1.2 is localized to
      the unmyelinated zone, whereas Na(v)1.6 is specifically targeted to nodes. During
      development, Na(v)1.2 is expressed first and becomes clustered at immature nodes
      of Ranvier, but as myelination proceeds, Na(v)1.6 replaces Na(v)1.2 at nodes. In
      Shiverer mice, which lack compact myelin, Na(v)1.2 is found throughout adult
      axons, whereas little Na(v)1.6 is detected. Together, these data show that sodium
      channel isoforms are differentially targeted to distinct domains of the same axon
      in a process associated with formation of compact myelin.

PMID- 11343648
TI  - Differential control of clustering of the sodium channels Na(v)1.2 and Na(v)1.6
      at developing CNS nodes of Ranvier.
AB  - Na(v)1.6 is the main sodium channel isoform at adult nodes of Ranvier. Here, we
      show that Na(v)1.2 and its beta2 subunit, but not Na(v)1.6 or beta1, are
      clustered in developing central nervous system nodes and that clustering of
      Na(v)1.2 and Na(v)1.6 is differentially controlled. Oligodendrocyte-conditioned
      medium is sufficient to induce clustering of Na(v)1.2 alpha and beta2 subunits
      along central nervous system axons in vitro. This clustering is regulated by
      electrical activity and requires an intact actin cytoskeleton and synthesis of a
      non-sodium channel protein. Neither soluble- or contact-mediated glial signals
      induce clustering of Na(v)1.6 or beta1 in a nonmyelinating culture system. These
      data reveal that the sequential clustering of Na(v)1.2 and Na(v)1.6 channels is
      differentially controlled and suggest that myelination induces Na(v)1.6
      clustering.

PMID- 11343649
TI  - Functional interaction between monoamine plasma membrane transporters and the
      synaptic PDZ domain-containing protein PICK1.
AB  - PDZ domain-containing proteins play an important role in the targeting and
      localization of synaptic membrane proteins. Here, we report an interaction
      between the PDZ domain-containing protein PICK1 and monoamine neurotransmitter
      transporters in vitro and in vivo. In dopaminergic neurons, PICK1 colocalizes
      with the dopamine transporter (DAT) and forms a stable protein complex.
      Coexpression of PICK1 with DAT in mammalian cells and neurons in culture results
      in colocalization of the two proteins in a cluster pattern and an enhancement of
      DAT uptake activity through an increase in the number of plasma membrane DAT.
      Deletion of the PDZ binding site at the carboxyl terminus of DAT abolishes its
      association with PICK1 and impairs the localization of the transporter in
      neurons. These findings indicate a role for PDZ-mediated protein interactions in
      the localization, expression, and function of monoamine transporters.

PMID- 11343650
TI  - Deregulation of Cdk5 in a mouse model of ALS: toxicity alleviated by perikaryal
      neurofilament inclusions.
AB  - Recent studies suggest that increased activity of cyclin-dependent kinase 5
      (Cdk5) may contribute to neuronal death and cytoskeletal abnormalities in
      Alzheimer's disease. We report here such deregulation of Cdk5 activity associated
      with the hyperphosphorylation of tau and neurofilament (NF) proteins in mice
      expressing a mutant superoxide dismutase (SOD1(G37R)) linked to amyotrophic
      lateral sclerosis (ALS). A Cdk5 involvement in motor neuron degeneration is
      supported by our analysis of three SOD1(G37R) mouse lines exhibiting perikaryal
      inclusions of NF proteins. Our results suggest that perikaryal accumulations of
      NF proteins in motor neurons may alleviate ALS pathogenesis by acting as a
      phosphorylation sink for Cdk5 activity, thereby reducing the detrimental
      hyperphosphorylation of tau and other neuronal substrates.

PMID- 11343651
TI  - Calcium influx via TRP channels is required to maintain PIP2 levels in Drosophila
      photoreceptors.
AB  - The trp (transient receptor potential) gene encodes a Ca2+ channel responsible
      for the major component of the phospholipase C (PLC) mediated light response in
      Drosophila. In trp mutants, maintained light leads to response decay and
      temporary total loss of sensitivity (inactivation). Using genetically targeted
      PIP2-sensitive inward rectifier channels (Kir2.1) as biosensors, we provide
      evidence that trp decay reflects depletion of PIP2. Two independent mutations in
      the PIP2 recycling pathway (rdgB and cds) prevented recovery from inactivation.
      Abolishing Ca2+ influx in wild-type photoreceptors mimicked inactivation, while
      raising Ca2+ by blocking Na+/Ca2+ exchange prevented inactivation in trp. The
      results suggest that Ca2+ influx prevents PIP2 depletion by inhibiting PLC
      activity and facilitating PIP2 recycling. Without this feedback one photon
      appears sufficient to deplete the phosphoinositide pool of approximately 4
      microvilli.

PMID- 11343652
TI  - Sequential SNARE assembly underlies priming and triggering of exocytosis.
AB  - Changes in SNARE conformations during MgATP-dependent priming of cracked PC12
      cells were probed by their altered accessibility to various inhibitors. Dominant
      negative soluble syntaxin and, to a much lesser extent, VAMP coil domains
      inhibited exocytosis more efficiently after priming. Neurotoxins and an anti
      SNAP25 antibody inhibited exocytosis less effectively after priming. We propose
      that SNAREs partially and reversibly assemble during priming, and that the
      syntaxin H3 domain is prevented from fully joining the complex until the arrival
      of the Ca2+ trigger. Furthermore, we find that mutation of hydrophobic residues
      of the SNAP25 C-terminal coil that contribute to SNARE core interactions affects
      the maximal rate of exocytosis, while mutation of charged residues on the surface
      of the complex affects the apparent affinity of the coil domain for the partially
      assembled complex.

PMID- 11343653
TI  - Fast kinetics of exocytosis revealed by simultaneous measurements of presynaptic
      capacitance and postsynaptic currents at a central synapse.
AB  - The rate of release from nerve terminals depends on both the number of release
      sites and the rate of release at each site. The latter remains largely unknown at
      central synapses. We addressed this issue by simultaneously measuring the nerve
      terminal membrane capacitance and the postsynaptic current at single calyceal
      synapses in rat brainstem. We found that a 10 ms presynaptic step depolarization
      depleted a releasable pool containing 3300-5200 vesicles. Released vesicles were
      endocytosed with a time constant of a few seconds to tens of seconds. Release of
      only one third of this pool saturated both postsynaptic AMPA and NMDA receptors.
      A release site can release more than three vesicles in 10 ms (>300 vesicles per
      second). We conclude that both a large number of release sites and a fast release
      rate at each site enable synapses to release at a high rate.

PMID- 11343654
TI  - Functional interaction of the active zone proteins Munc13-1 and RIM1 in synaptic
      vesicle priming.
AB  - Synaptic neurotransmitter release is restricted to active zones, where the
      processes of synaptic vesicle tethering, priming to fusion competence, and Ca2+
      triggered fusion are taking place in a highly coordinated manner. We show that
      the active zone components Munc13-1, an essential vesicle priming protein, and
      RIM1, a Rab3 effector with a putative role in vesicle tethering, interact
      functionally. Disruption of this interaction causes a loss of fusion-competent
      synaptic vesicles, creating a phenocopy of Munc13-1-deficient neurons. RIM1
      binding and vesicle priming are mediated by two distinct structural modules of
      Munc13-1. The Munc13-1/RIM1 interaction may create a functional link between
      synaptic vesicle tethering and priming, or it may regulate the priming reaction
      itself, thereby determining the number of fusion-competent vesicles.

PMID- 11343655
TI  - Nucleoside diphosphate kinase, a source of GTP, is required for dynamin-dependent
      synaptic vesicle recycling.
AB  - Nucleoside diphosphate kinase (NDK), an enzyme encoded by the Drosophila abnormal
      wing discs (awd) or human nm23 tumor suppressor genes, generates nucleoside
      triphosphates from respective diphosphates. We demonstrate that NDK regulates
      synaptic vesicle internalization at the stage where function of the dynamin
      GTPase is required. awd mutations lower the temperature at which behavioral
      paralysis, synaptic failure, and blocked membrane internalization occur at
      dynamin-deficient, shi(ts), mutant nerve terminals. Hypomorphic awd alleles
      display shi(ts)-like defects. NDK is present at synapses and its enzymatic
      activity is essential for normal presynaptic function. We suggest a model in
      which dynamin activity in nerve terminals is highly dependent on NDK-mediated
      supply of GTP. This connection between NDK and membrane internalization further
      strengthens an emerging hypothesis that endocytosis, probably of activated growth
      factor receptors, is an important tumor suppressor activity in vivo.

PMID- 11343656
TI  - Extrasynaptic release of dopamine in a retinal neuron: activity dependence and
      transmitter modulation.
AB  - Extrasynaptic release of dopamine is well documented, but its relation to the
      physiological activity of the neuron is unclear. Here we show that in absence of
      presynaptic active zones, solitary cell bodies of retinal dopaminergic neurons
      release by exocytosis packets of approximately 40,000 molecules of dopamine at
      irregular intervals and low frequency. The release is triggered by the action
      potentials that the neurons generate in a rhythmic fashion upon removal of all
      synaptic influences and therefore depends upon the electrical events at the
      neuronal surface. Furthermore, it is stimulated by kainate and abolished by GABA
      and quinpirole, an agonist at the D(2) dopamine receptor. Since the somatic
      receptors for these ligands are extrasynaptic, we suggest that the composition of
      the extracellular fluid directly modulates extrasynaptic release.

PMID- 11343657
TI  - Selective targeting of newly synthesized Arc mRNA to active synapses requires
      NMDA receptor activation.
AB  - Newly synthesized Arc mRNA is selectively targeted to synapses that have
      experienced particular patterns of activity. Here, we demonstrate that the
      targeting requires NMDA receptor activation. Arc expression was induced by an
      electroconvulsive seizure, and the newly synthesized mRNA was then targeted to
      synaptic sites by activating the perforant path projections to the dentate gyrus.
      When micropipette electrodes containing NMDA receptor antagonists (MK801 or APV)
      were positioned in the dentate gyrus during the stimulation period, newly
      synthesized Arc mRNA was transported into dendrites but did not localize in the
      activated lamina; instead, the mRNA remained diffusely distributed. AMPA receptor
      antagonists (CNQX) blocked targeting of Arc mRNA in a small region, and mGluR
      antagonists (MCPG) did not affect localization. These results demonstrate that
      NMDA receptor activation is required for the targeting of Arc mRNA to active
      synapses.

PMID- 11343658
TI  - Ca2+ signaling via the neuronal calcium sensor-1 regulates associative learning
      and memory in C. elegans.
AB  - On a radial temperature gradient, C. elegans worms migrate, after conditioning
      with food, toward their cultivation temperature and move along this isotherm.
      This experience-dependent behavior is called isothermal tracking (IT). Here we
      show that the neuron-specific calcium sensor-1 (NCS-1) is essential for optimal
      IT. ncs-1 knockout animals show major defects in IT behavior, although their
      chemotactic, locomotor, and thermal avoidance behaviors are normal. The knockout
      phenotype can be rescued by reintroducing wild-type NCS-1 into the AIY
      interneuron, a key component of the thermotaxis network. A loss-of-function form
      of NCS-1 incapable of binding calcium does not restore IT, whereas NCS-1
      overexpression enhances IT performance levels, accelerates learning (faster
      acquisition), and produces a memory with slower extinction. Thus, proper calcium
      signaling via NCS-1 defines a novel pathway essential for associative learning
      and memory.

PMID- 11343659
TI  - The circadian clock of fruit flies is blind after elimination of all known
      photoreceptors.
AB  - Circadian rhythms are entrained by light to follow the daily solar cycle. We show
      that Drosophila uses at least three light input pathways for this entrainment:
      (1) cryptochrome, acting in the pacemaker cells themselves, (2) the compound
      eyes, and (3) extraocular photoreception, possibly involving an internal
      structure known as the Hofbauer-Buchner eyelet, which is located underneath the
      compound eye and projects to the pacemaker center in the brain. Although
      influencing the circadian system in different ways, each input pathway appears
      capable of entraining circadian rhythms at the molecular and behavioral level.
      This entrainment is completely abolished in glass(60j) cry(b) double mutants,
      which lack all known external and internal eye structures in addition to being
      devoid of cryptochrome.

PMID- 11343660
TI  - Prediction of orientation selectivity from receptive field architecture in simple
      cells of cat visual cortex.
AB  - From the intracellularly recorded responses to small, rapidly flashed spots, we
      have quantitatively mapped the receptive fields of simple cells in the cat visual
      cortex. We then applied these maps to a feedforward model of orientation
      selectivity. Both the preferred orientation and the width of orientation tuning
      of the responses to oriented stimuli were well predicted by the model. Where
      tested, the tuning curve was well predicted at different spatial frequencies. The
      model was also successful in predicting certain features of the spatial frequency
      selectivity of the cells. It did not successfully predict the amplitude of the
      responses to drifting gratings. Our results show that the spatial organization of
      the receptive field can account for a large fraction of the orientation
      selectivity of simple cells.

PMID- 11343661
TI  - Sleep enhances plasticity in the developing visual cortex.
AB  - During a critical period of brain development, occluding the vision of one eye
      causes a rapid remodeling of the visual cortex and its inputs. Sleep has been
      linked to other processes thought to depend on synaptic remodeling, but a role
      for sleep in this form of cortical plasticity has not been demonstrated. We found
      that sleep enhanced the effects of a preceding period of monocular deprivation on
      visual cortical responses, but wakefulness in complete darkness did not do so.
      The enhancement of plasticity by sleep was at least as great as that produced by
      an equal amount of additional deprivation. These findings demonstrate that sleep
      and sleep loss modify experience-dependent cortical plasticity in vivo. They
      suggest that sleep in early life may play a crucial role in brain development.

PMID- 11343662
TI  - Human hippocampal neurons predict how well word pairs will be remembered.
AB  - What is the neuronal basis for whether an experience is recalled or forgotten? In
      contrast to recognition, recall is difficult to study in nonhuman primates and
      rarely is accessible at the single neuron level in humans. We recorded 128 medial
      temporal lobe (MTL) neurons in patients implanted with intracranial
      microelectrodes while they encoded and recalled word paired associates. Neurons
      in the amygdala, entorhinal cortex, and hippocampus showed altered activity
      during encoding (9%), recall (22%), and both task phases (23%). The responses of
      hippocampal neurons during encoding predicted whether or not subjects later
      remembered the pairs successfully. Entorhinal cortex neuronal activity during
      retrieval was correlated with recall success. These data provide support at the
      single neuron level for MTL contributions to encoding and retrieval, while also
      suggesting there may be differences in the level of contribution of MTL regions
      to these memory processes.

PMID- 11343664
TI  - Does the location of thrombosis determine the risk of disease recurrence in
      patients with proximal deep vein thrombosis?
AB  - PURPOSE: To determine if the location of deep vein thrombosis is a predictor of
      recurrent venous thromboembolism during the initial 3 months of anticoagulant
      therapy. METHODS: The study population consisted of 1,149 consecutive patients
      with symptomatic proximal deep vein thrombosis. In all patients, deep vein
      thrombosis was confirmed by Duplex ultrasound or venography and was classified as
      popliteal, femoral, or iliofemoral. Patients received initial treatment with
      unfractionated heparin, enoxaparin, or reviparin for least 4 days, as well as a
      coumarin derivative, with a target international normalized ratio of 2.0 to 3.0,
      starting on the 1st or 2nd day of treatment. All patients were followed for 3
      months, and all episodes of recurrent venous thromboembolism were confirmed with
      objective diagnostic tests. RESULTS: The overall rate of recurrent venous
      thromboembolism during the initial 3 months of anticoagulant therapy was 5.5%
      (63/1,149). The rate of recurrence in patients with popliteal vein thrombosis was
      5.1% (23/453); in patients with femoral vein thrombosis, it was 5.3% (34/645);
      and in patients with iliofemoral vein thrombosis, it was 11.8% (6/51). Two
      clinical risk factors were associated with an increased risk of recurrent venous
      thromboembolism: iliofemoral vein thrombosis (odds ratio [OR] = 2.4; 95%
      confidence interval [CI]: 0.95, 5.9), and cancer (OR = 2.6; 95% CI: 1.5, 4.4).
      CONCLUSIONS: Patients with extensive iliofemoral vein thrombosis who receive
      conventional anticoagulant therapy have a greater than twofold higher risk of
      developing recurrent venous thromboembolism than patients without iliac vein
      involvement (i.e., 11.8% vs. 5.2%). Prospective studies are needed to determine
      whether alternative antithrombotic strategies are warranted in such patients.

PMID- 11343665
TI  - Diagnosis of cardiac sarcoidosis and evaluation of the effects of steroid therapy
      by gadolinium-DTPA-enhanced magnetic resonance imaging.
AB  - BACKGROUND: Cardiac involvement is an important prognostic factor in patients
      with sarcoidosis. In this study, we evaluated the usefulness of gadolinium-DTPA
      (diethylene triamine pentaacetic acid)-enhanced magnetic resonance imaging (Gd
      MRI) for diagnosing cardiac sarcoidosis and evaluating the effects of steroid
      therapy. METHODS: Sixteen patients with sarcoidosis diagnosed by histology or by
      Japanese Ministry of Health and Welfare criteria for cardiac sarcoidosis
      underwent Gd-MRI with a 1.5-Tesla superconducting magnet system using a T1
      weighted spin-echo sequence. RESULTS: Gd-MRI showed localized enhancement of
      signal intensity, indicating interstitial edema, in the left ventricle in 8 of
      the 16 patients. Two patients with enhancement also had thinning of the left
      ventricular septal wall. After 1 month of prednisolone therapy (60 mg every other
      day or 30 to 40 mg every day), the localized high-intensity signals were markedly
      diminished in all 8 patients. CONCLUSIONS: Images of the heart obtained by Gd-MRI
      may reflect active inflammation with interstitial edema in patients with
      sarcoidosis. Gd-MRI may be a useful noninvasive method for early detection of
      cardiac sarcoidosis and for evaluating the effects of steroid therapy.

PMID- 11343666
TI  - Value of transthoracic echocardiography in the diagnosis of pulmonary embolism:
      results of a prospective study in unselected patients.
AB  - PURPOSE: Echocardiography is advocated by some as a useful diagnostic test for
      patients with suspected pulmonary embolism (PE), but its diagnostic accuracy is
      unknown. The present study was undertaken to determine prospectively the
      sensitivity and specificity of transthoracic echocardiography in the diagnosis of
      PE. SUBJECTS AND METHODS: We examined 110 consecutive patients with suspected PE.
      The study protocol included assessment of clinical probability, echocardiography,
      and perfusion lung scanning. Pulmonary angiography was performed in all patients
      with abnormal scans. As echocardiographic criteria to diagnose acute PE, we used
      the presence of any two of the following: right ventricular (RV) hypokinesis, RV
      end-diastolic diameter >27 mm (without RV wall hypertrophy), or tricuspid
      regurgitation velocity >2.7 m/sec. Clinical estimates of PE served as pretest
      probabilities in calculating, after echocardiography, the posttest probabilities
      of PE. RESULTS: Pulmonary angiography confirmed PE in 43 (39%) of 110 patients.
      Echocardiographic diagnostic criteria for PE yielded a sensitivity of 56% and a
      specificity of 90%. For pretest probabilities of 10%, 50%, and 90%, the posttest
      probabilities of PE conditioned by a positive echocardiogram were 38%, 85%, and
      98%, respectively. The posttest probabilities of PE conditioned by a negative
      echocardiogram were 5%, 33%, and 81%, respectively. CONCLUSIONS: In unselected
      patients with suspected PE, transthoracic echocardiography fails to identify some
      50% of patients with angiographically proven PE. Although echocardiographic
      findings of RV strain, paired with a high clinical likelihood, support a
      diagnosis of PE, the transthoracic echocardiography has to have a better
      sensitivity to be used as a screening test to rule out PE.

PMID- 11343667
TI  - Effect of folic acid treatment on endothelium-dependent vasodilation and nitric
      oxide-derived end products in hyperhomocysteinemic subjects.
AB  - PURPOSE: An elevated plasma homocysteine concentration is an independent risk
      factor for cardiovascular diseases. In this study, we tested the hypothesis that
      hyperhomocysteinemia induces endothelial dysfunction mediated, at least in part,
      through nitric oxide-dependent mechanisms and that folic acid supplementation
      improves endothelial function in hyperhomocysteinemic subjects. SUBJECTS AND
      METHODS: Endothelial function was evaluated in healthy controls and
      hyperhomocysteinemic subjects by measuring plasma levels of the nitric oxide
      derived end products nitrite and nitrate and by assessing vasodilatory responses
      in the skin microcirculation and forearm vasculature. In the subjects with
      hyperhomocysteinemia, these measurements were repeated after 6 weeks and 12
      months of folic acid supplementation. RESULTS: Compared with healthy controls,
      hyperhomocysteinemic subjects had significantly lower median plasma levels of
      nitric oxide-derived end products (12.1 microM [range 4.4 to 41.8] versus 24.6
      microM [13.6 to 53.2]; P <0.001), a significantly lower endothelium-dependent
      vasodilatory response to acetylcholine (P <0.01), hyperemic response in the
      microcirculation (P <0.01), and total forearm blood flow during reactive
      hyperemia (P = 0.01). There was no significant difference in the endothelium
      independent response. Folic acid treatment for 12 months increased the plasma
      level of nitric oxide-derived end products by 121% (95% confidence interval [CI],
      72% to 170%), the vasodilatory response to acetylcholine by 124% (95% CI, 36% to
      212%), and the ischemia-mediated hyperemic responses in the microcirculation by
      60% (95% CI, 25% to 96%) and in the forearm vasculature by 47% (95% CI, 21% to
      73%). CONCLUSIONS: Homocysteine appears to induce its atherogenic effect, at
      least in part, by depressing endothelial function, possibly through nitric oxide
      dependent mechanisms. This effect can be reversed by folic acid supplementation.

PMID- 11343668
TI  - A case-management program of medium intensity does not improve cardiovascular
      risk factor control in coronary artery disease patients: the Heartcare I trial.
AB  - BACKGROUND: Case-management programs for secondary prevention of coronary artery
      disease that utilize extensive resources can reduce cardiovascular risk factors,
      but less intensive approaches have failed to show benefits. This randomized trial
      evaluated whether a medium intensity case-management program improves risk factor
      control in patients with coronary artery disease. METHODS: We assigned 201
      consecutive patients hospitalized for acute coronary events in the intensive care
      unit of University Hospital, Basel, Switzerland, to either a risk factor case
      management program (n = 99) or care as usual (n = 102) using the patients'
      primary care physicians as the unit of randomization (cluster randomization). The
      case-management program consisted of an hour of counseling by a clinician during
      hospitalization and two short reminders by phone and mail 3 and 6 months later.
      Treatment decisions were left to patients and their primary care physicians.
      RESULTS: After 9 and 18 months of follow-up, there were no significant
      differences in lipid values, blood pressure control, fasting blood glucose, body
      mass index, or number of smokers between the two groups. However, significantly
      more patients in the intervention group than in the care as usual group achieved
      target cholesterol values after 18 months (48% versus 27%, P = 0.002 and remained
      significant after Bonferroni-Holms correction) but not after 9 months of follow
      up (31% versus 27%, P >0.2). CONCLUSION: This hospital-based case-management and
      outreach program, limited to counseling by a clinician, did not substantially
      improve cardiovascular risk factor control among patients hospitalized for
      coronary events.

PMID- 11343669
TI  - Management of small renal tumors: an overview.
AB  - The incidental finding of a small renal mass poses a therapeutic dilemma. The
      traditional treatment of clinically important masses has been radical
      nephrectomy. Recently, nephron-sparing surgery has emerged as a viable
      alternative; and experimental minimally invasive percutaneous tissue ablation
      techniques, including cryotherapy and radiofrequency ablation, are being
      evaluated. In this review, we discuss the dilemma posed by frequent renal imaging
      and the increased proportion of incidental tumors being detected, the limitations
      of needle biopsies for histologic diagnosis, nephron-conserving and minimally
      invasive surgery, and the possible merits of radiofrequency ablation and
      cryotherapy. We envision a defined role for minimally invasive percutaneous or
      extracorporeal ablation of small renal tumors.

PMID- 11343670
TI  - Hypogonadism and androgen replacement therapy in elderly men.
AB  - The decrease in testosterone levels with age is both central (pituitary) and
      peripheral (testicular) origin. Because serum levels of sex-hormone-binding
      globulin increase with aging, the decrease in free testosterone is of even
      greater magnitude. Recent long-term studies of testosterone therapy in
      hypogonadal elderly men have shown beneficial effects on bone density, body
      composition, and muscle strength without any substantial adverse effects on
      lipids and the prostate. Total testosterone level is the test of choice for
      initial screening of elderly men who present with signs and symptoms of
      hypogonadism. If the level is below 300 ng/dL, replacement therapy should be
      initiated. If the level is normal in a symptomatic patient, free or bioavailable
      testosterone should be determined. The pros and cons of testosterone therapy
      should be discussed in depth with every patient, and decisions should be made on
      an individual basis. This review summarizes the trials of testosterone
      replacement therapy in elderly men and outlines a diagnostic approach to these
      patients.

PMID- 11343671
TI  - The Brugada syndrome: clinical, genetic, cellular, and molecular abnormalities.
AB  - The Brugada syndrome is an arrhythmic syndrome characterized by a right bundle
      branch block pattern and ST segment elevation in the right precordial leads of
      the electrocardiogram in conjunction with a high incidence of sudden death
      secondary to ventricular tachyarrhythmias. No evidence of structural heart
      disease is noted during diagnostic evaluation of these patients. In 25% of
      families, there appears to be an autosomal dominant mode of transmission with
      variable expression of the abnormal gene. Mutations have been identified in the
      gene that encodes the alpha subunit of the sodium channel (SCN5A) on chromosome
      3. This genetic defect causes a reduction in the density of the sodium current
      and explains the worsening of the above electrocardiographic abnormalities when
      patients are treated with sodium channel blocking antiarrhythmic agents, which
      further diminish the already reduced sodium current. The prognosis is poor with
      up to a 10% per year mortality. Antiarrhythmic drugs including beta-blockers and
      amiodarone have no benefit in prolonging survival. The treatment of choice is the
      insertion of an implantable cardioverter-defibrillator.

PMID- 11343672
TI  - Long-term treatment of patients with inappropriate secretion of antidiuretic
      hormone by the vasopressin receptor antagonist conivaptan, urea, or furosemide.

PMID- 11343673
TI  - Effects of 1-year treatment with fluvastatin or pravastatin on bone.

PMID- 11343675
TI  - The dark side of deep venous thrombosis: the failure of anticoagulation.

PMID- 11343676
TI  - Gadolinium-enhanced cardiac magnetic resonance imaging: expanding the spectrum of
      clinical applications.

PMID- 11343677
TI  - To err is preventable: medical errors and academic medicine.

PMID- 11343678
TI  - Brain structure, genetic liability, and psychotic symptoms in subjects at high
      risk of developing schizophrenia.
AB  - BACKGROUND: Structural magnetic resonance imaging (MRI) of the brain in patients
      with schizophrenia has consistently demonstrated several abnormalities. These are
      thought to be neurodevelopmental in origin, as they have also been described in
      first episode cases, although there may be a progressive component. It is not
      known at which point in development these abnormalities are evident, nor to what
      extent they are genetically or environmentally mediated. METHODS: One hundred
      forty-seven high-risk subjects (with at least two affected first or second degree
      relatives), 34 patients in their first episode, and 36 healthy control subjects
      received an MRI scan covering the whole brain. After inhomogeneity correction,
      regions of interest were traced by three group-blind raters with good inter-rater
      reliability. Regional brain volumes were related to measures of genetic liability
      to schizophrenia and to psychotic symptoms elicited at structured psychiatric
      interviews. RESULTS: High-risk subjects had statistically significantly reduced
      mean volumes of the left and right amygdalo-hippocampus and thalamus, as compared
      to healthy control subjects. They also had bilaterally larger amygdalo-hippocampi
      and bilaterally smaller lenticular nuclei than the schizophrenics. High-risk
      subjects with symptoms had smaller brains than those without. The volumes of the
      prefrontal lobes and the thalamus were the only consistent associates of genetic
      liability. CONCLUSIONS: Subjects at high risk of developing schizophrenia have
      abnormalities of brain structure similar to but not identical to those found in
      schizophrenia. Our results suggest that some structural abnormalities are genetic
      trait or vulnerability markers, others are environmentally mediated, and that the
      development of symptoms is associated with a third overlapping group of
      structural changes. Particular risk factors for schizophrenia may interact at
      discrete time points of neurodevelopment with different effects on specific brain
      regions and may represent relatively distinct disease processes.

PMID- 11343679
TI  - Structural magnetic imaging of the hippocampus in early onset schizophrenia.
AB  - BACKGROUND: Previous literature suggests that hippocampal volume reductions in
      schizophrenia may occur either during adolescence or at the point of transition
      to overt psychosis. The authors tested these hypotheses by examining the
      hippocampal formation in adolescents with recent onset schizophrenia. METHODS: We
      compared the volumes of the left and right hippocampus, obtained using
      stereologic methods from magnetic resonance brain images, from 40 adolescents
      with recent onset schizophrenia to those of an equal number of matched healthy
      control subjects. Symptoms were rated using the Positive and Negative Syndrome
      Scale. RESULTS: Compared with control subjects, adolescents with schizophrenia
      had reduced whole brain volume. After adjusting for brain volume, no group
      differences were observed in hippocampal volume. Duration of illness was
      negatively correlated with the volume of the left hippocampus. We found no effect
      of pregnancy and birth complications or family history of psychosis on
      hippocampal volumes. There was a negative correlation between severity of
      psychopathology and hippocampal volumes, which was significant for negative
      symptoms. CONCLUSIONS: Specific hippocampal volume reductions in early onset
      schizophrenia do not seem to predate the onset of or to occur at the point of
      transition to psychosis but may develop in adolescence during the early stages of
      the illness.

PMID- 11343680
TI  - Event-related brain potentials (ERPs) in schizophrenia for tonal and phonetic
      oddball tasks.
AB  - BACKGROUND: Prior studies using simple target detection ("oddball") tasks with
      pure tones have reported asymmetric reduction of the P3 event-related potential
      (ERP). This study investigated the time course and topography of ERPs recorded
      during both tonal and phonetic oddball tasks. METHODS: Event-related potentials
      of 66 patients (14 unmedicated) diagnosed with schizophrenia (n = 46) or
      schizoaffective disorder (n = 20) and 32 healthy adults were recorded from 30
      scalp electrodes during two oddball tasks using consonant-vowel syllables or
      complex tones. Overlapping ERP components were identified and measured by
      covariance-based principal components analysis. RESULTS: Schizophrenic patients
      showed marked, task-independent reductions of early negative potentials (N1, N2)
      but not reduced P3 amplitude or abnormal P3 asymmetry. Task-related hemispheric
      asymmetries of the N2/P3 complex were similar in healthy adults and schizophrenic
      patients. Poorer task performance in patients was related to ERP amplitudes, but
      could not account for reductions of early negativities. CONCLUSIONS: The findings
      suggest that both patients and control subjects activated lateralized cortical
      networks required for pitch (right frontotemporal) and phoneme (left
      parietotemporal) discrimination. Task-independent reductions of negativities
      between 80 and 280 msec after stimulus onset suggest a deficit of automatic
      stimulus classification in schizophrenia, which may be partly compensated by
      later effortful processing.

PMID- 11343681
TI  - N1 and P300 abnormalities in patients with schizophrenia, epilepsy, and epilepsy
      with schizophrenialike features.
AB  - BACKGROUND: The scalp-recorded N1 and P300 components of the event-related brain
      potential (ERP) are commonly reduced in patients with schizophrenia but not in
      patients with epilepsy. Epilepsy patients with interictal chronic
      schizophrenialike features (EPI-SZ) provide a comparison group for determining
      whether the ERP amplitude abnormalities seen in schizophrenic patients are
      associated with shared clinical features of EPI-SZ and schizophrenic patients or
      overlapping pathophysiologies, or are specific to a distinct schizophrenia
      etiology. METHODS: Patients with schizophrenia (n = 24) were compared with normal
      control subjects (n = 32) and patients with epilepsy syndromes on visual and
      auditory oddball ERP paradigms. Epilepsy patients included those with chronic
      interictal schizophrenialike features (n = 6) and those without (n = 16).
      RESULTS: Auditory P300 amplitude was reduced in both schizophrenic and EPI-SZ
      patients, whose positive or negative symptoms did not differ. In contrast, N1
      amplitude was reduced only in schizophrenic patients. Delays in both N1 and P300
      were associated with epilepsy patients and EPI-SZ but not schizophrenic patients.
      CONCLUSIONS: The schizophrenialike symptoms in epilepsy probably represent a
      phenocopy of schizophrenia with common clinical features and some common
      pathophysiologies but distinct etiologies. P300 amplitude appears to be sensitive
      to schizophrenialike features, regardless of whether they occur in the context of
      schizophrenia or epilepsy. N1 amplitude reduction appears to be specific to
      schizophrenia, suggesting its sensitivity to the distinct etiology of
      schizophrenia.

PMID- 11343682
TI  - The effect of tandospirone, a serotonin(1A) agonist, on memory function in
      schizophrenia.
AB  - BACKGROUND: The purpose of this study was to test the hypothesis that the
      addition of tandospirone, a 5-HT(1A) partial agonist, to ongoing treatment with
      typical antipsychotic drugs, would improve memory function in patients with
      schizophrenia. METHODS: Eleven outpatients (male/female = 7/4) with schizophrenia
      who had been on stable doses of haloperidol and biperiden were given
      tandospirone, 30 mg/day, for 4 weeks. The Wechsler Memory Scale-Revised (WMS-R)
      was administered at baseline and 4 weeks after the addition of tandospirone. The
      Brief Psychiatric Rating Scale (BPRS; Total, Positive, and Negative subscale
      scores) and the Simpson-Angus Scale for Extrapyramidal Symptoms (SAS) were also
      completed on the two occasions. To exclude the possibility of a practice effect
      on the WMS-R test, 11 age-matched patients with schizophrenia (M/F = 7/4) were
      tested at baseline and after a 4-week interval. RESULTS: Repeated measures
      analysis of variance revealed a significant time by group (patients with or
      without tandospirone) effect for the Verbal-, but not the Visual Memory composite
      scores of the WMS-R test; no significant change was observed in patients without
      tandospirone, whereas improvement in the Verbal Memory score was noted in
      patients receiving tandospirone. Moreover, there was improvement in the Inclusion
      score, an index of memory organization as measured by the Logical Memory subtest
      of WMS-R, only in patients with tandospirone. Scores on the BPRS and SAS were
      improved during treatment with tandospirone, but the effects did not reach
      statistical significance. CONCLUSIONS: The results suggest that adjunctive
      treatment with 5-HT(1A) agonists may improve some types of memory function in
      schizophrenia.

PMID- 11343683
TI  - Long-term outcome of patients who receive ketamine during research.
AB  - BACKGROUND: To comprehend the pathophysiology of schizophrenia and to facilitate
      drug discovery, animal and human models of schizophrenia are necessary. Ketamine,
      a noncompetitive N-methyl-D-aspartate antagonist, has been used to probe
      glutamatergic function in normal and schizophrenic volunteers. These studies and
      others have provided data consistent with a putative involvement of a
      glutamatergic dysfunction in the pathophysiology of schizophrenia; however, these
      studies have also raised concerns about the distress inflicted on patients, the
      potential for adverse events, and the serious long-term effects that could
      possibly be induced by symptom-simulating action. METHODS: For all patient
      volunteers (n = 30) who participated in these studies, we reviewed the acute
      safety during and in the immediate postketamine administration. Patients
      available for long-term follow-up (n = 25) were matched to a group of patients (n
      = 25) who participated in research but did not receive ketamine. We compared
      their long-term outcome in terms of psychopathology, the need for psychiatric
      care, and the amount of antipsychotic medication required for optimal therapeutic
      response. RESULTS: There were no serious adverse events in more than 90 ketamine
      interviews. Distress to patients was minimal, which is shown by the lack of
      anxiety ratings. Over a mean follow-up period of 8 months, we found no
      differences between patients who did and did not receive ketamine on any measures
      of psychopathology, psychiatric care, or the amount of antipsychotic medication.
      CONCLUSIONS: In a controlled environment and paying close attention to subject
      safety features, administering subanesthetic doses of ketamine causes no adverse
      events and little distress to schizophrenic volunteers. This study strongly
      indicates that administering ketamine does not change any aspect of the course of
      schizophrenic illness.

PMID- 11343684
TI  - Chronic high-dose glycine nutrition: effects on rat brain cell morphology.
AB  - BACKGROUND: Facilitation of N-methyl-D-aspartate (NMDA) receptor-mediated
      neurotransmission via administration of glycine site agonists of the NMDA
      receptor (e.g., glycine, D-serine), and glycine transport inhibitors may
      represent an innovative pharmacologic strategy in schizophrenia; however, given
      the potential involvement of NMDA receptors in the neurotoxicity of excitatory
      amino acids, possible neurotoxic effects of glycinergic compounds need to be
      explored. Furthermore, studying brain adaptations to chronic administration of
      glycine site agonists may provide insights into the therapeutic mechanisms of
      these drugs. METHODS: Adult rats were randomized to one of three nutritional
      regimens (no glycine supplementation, 1 g/kg/day, or 5 g/kg/day glycine
      supplementation) and to one of three treatment durations (1, 3, or 5 months).
      Serum glycine and serine levels at sacrifice and brain sections were examined
      using histologic markers of neurodegeneration (cresyl violet and silver
      impregnation staining) and immunohistochemical staining of glial fibrillary
      acidic protein, microtubule-associated protein, and neurofilament 200. To explore
      additional neural adaptations to high-dose glycine treatment, immunostaining was
      also performed for class B, N-type Ca(2+) channels. RESULTS: Serum glycine levels
      increased dose dependently during glycine nutrition, whereas serine levels were
      not changed. In hippocampal dentate gyrus, the percentage of hypertrophied
      astrocytes transiently increased at 1 month. At 3 and 5 months of glycine
      treatment, the density of class B, N-type Ca(2+) channels was reduced in parietal
      cortex and hippocampus. No evidence of neuronal or glial cell excitotoxic damage
      or degeneration was registered at either of the treatment intervals studied.
      CONCLUSIONS: These findings demonstrate for the first time that in vivo
      administration of high-dose glycine may induce brain morphological changes
      without causing neurotoxic effects. A reduction in density of class B, N-type
      Ca(2+) channels in specific brain regions may represent one general adaptation to
      long-term, high-dose glycine treatment.

PMID- 11343685
TI  - Human 5-HT(5) receptors: the 5-HT(5A) receptor is functional but the 5-HT(5B)
      receptor was lost during mammalian evolution.
AB  - We have isolated from a human genomic library the human 5-hydroxytryptamine 5
      HT(5A) and 5-HT(5B) genes. The human 5-HT(5A) gene encodes a protein with similar
      characteristics to its mouse homologue. When expressed in monkey COS-7 cells, the
      human 5-HT(5A) receptor displayed a high affinity for tritiated 5
      carbamidotryptamine ([3H]5-CT; K(D)=2.8 nM) and iodinated lysergic acid
      diethylamide ([125I]LSD; K(D)=187 pM). These binding sites displayed the
      following displacement profile: Ergotamine>Methiothepin>5-CT, Ritanserin>5-HT.
      Reverse transcriptase polymerase chain reaction (RT-PCR) experiments revealed the
      presence of human 5-HT(5A) mRNA in the central nervous system but not in
      peripheral organs. When expressed in Xenopus oocytes, the 5-HT(5A) receptor was
      able to couple to the inwardly rectifying K(+) channel, GIRK(1). In contrast to
      the human 5-HT(5A) gene and the mouse 5-HT(5B) gene, the human 5-HT(5B) gene does
      not encode a functional protein because its coding sequence is interrupted by
      stop codons. Our results suggest, therefore, that the 5-HT(5B) receptor has been
      lost during evolution after the divergence between rodents and primates. The 5
      HT(5B) receptor is the first example of a brain-specific protein that is absent
      in human.

PMID- 11343686
TI  - Direct inhibition of voltage-dependent Ca(2+) fluxes by ethanol and higher
      alcohols in rabbit T-tubule membranes.
AB  - The effects of ethanol and higher alcohols on 45Ca(2+) fluxes, mediated by
      voltage-dependent Ca(2+) channels (VDCCs), were investigated in inside-out
      transverse (T)-tubule membrane vesicles from rabbit skeletal muscle. 45Ca(2+)
      effluxes were induced by membrane potentials generated via establishing K(+)
      gradients across the vesicles, and were significantly inhibited by the inorganic
      Ca(2+) channel blocker La(3+) (1 mM) and the Ca(2+) channel antagonist nifedipine
      (1-10 microM). Ethanol, in the concentration range of 100-400 mM, caused a
      significant suppression of depolarization-induced 45Ca(2+) fluxes. Ethanol also
      functionally modulated the effect of nifedipine (1-10 microM) and the Ca(2+)
      channel agonist Bay K 8644 (1 microM) on Ca(2+) effluxes. Pretreatment with
      pertussis toxin (5 microg/ml) or phorbol 12-myrstate 13-acetate (PMA, 50 nM) did
      not affect the ethanol inhibition of 45Ca(2+) fluxes. Further experiments with
      alcohols revealed that butanol, hexanol, octanol and decanol also significantly
      inhibited 45Ca(2+) effluxes. However, undecanol and dodecanol did not cause any
      significant change on 45Ca(2+) fluxes, indicating that the effects of alcohols on
      45Ca(2+) effluxes exhibit a cut-off phenomenon. In radioligand binding studies,
      it was found that at the concentrations used in flux studies, alcohols did not
      alter the characteristics of the specific binding of [3H]PN 200-110 to T-tubule
      membranes. Results indicate that ethanol directly inhibits the function of
      voltage-dependent Ca(2+) channels without modulating the specific binding of
      Ca(2+) channel ligands of the dihydropyridine class, and that this inhibition is
      independent of intracellular Ca(2+) levels.

PMID- 11343687
TI  - The noradrenaline-dopamine interaction in the rat medial prefrontal cortex
      studied by multi-probe microdialysis.
AB  - Multi-probe microdialysis was used to investigate the interaction between the
      release of noradrenaline and dopamine in the medial prefrontal cortex. Retrograde
      microdialysis was used to stimulate or inhibit the activity of the locus
      coeruleus for a restricted period of time, and the response of extracellular
      noradrenaline and dopamine in the ipsilateral and contralateral medial prefrontal
      cortex was recorded with microdialysis probes. Infusion of clonidine into the
      locus coeruleus (100 microM for 45 min) suppressed noradrenaline release and
      slightly inhibited dopamine release in the ipsilateral medial prefrontal cortex.
      Application of carbachol to the locus coeruleus (100 microM for 45 min)
      stimulated both the noradrenaline and dopamine release in the ipsilateral medial
      prefrontal cortex. No changes were seen in the contralateral medial prefrontal
      cortex. In the ipsilateral nucleus accumbens, extracellular noradrenaline levels
      increased, but dopamine levels remained unchanged. Application to the locus
      coeruleus (during 10 min) of the glutamate receptor agonists N-methyl-D-aspartate
      (NMDA) (300 microM) or kainate (100 microM) strongly increased extracellular
      noradrenaline and dopamine levels in the ipsilateral medial prefrontal cortex.
      However, in the contralateral probe the release of dopamine (but not of
      noradrenaline) was also stimulated. Application of carbachol to the locus
      coeruleus was used as a model to further investigate the presumed noradrenaline
      dopamine interaction. In a series of dual-probe experiments, alpha(1)-, alpha(2)
      , and beta-adrenoceptor antagonists (prazosin, idazoxan, propranolol) or a
      reuptake-inhibitor (nomifensine) was administered during carbachol stimulation of
      the locus coeruleus. Prazosin and propranolol were administered systemically in a
      dose of 3 mg/kg, whereas idazoxan (10 microM) and nomifensine (100 microM) were
      infused into the medial prefrontal cortex. However, none of these pretreatments
      modified the effects of the control carbachol-infusions. The results did not
      identify a receptor-interaction or a common reuptake site that explained the
      presumed interaction between dopamine and noradrenaline in the medial prefrontal
      cortex. Therefore, the noradrenaline-dopamine interaction hypothesis could not be
      confirmed or refuted.

PMID- 11343688
TI  - Stimulatory effects of centrally injected kappa-opioid receptor agonists on
      gastric acid secretion in urethane-anesthetized rats.
AB  - Gastric acid secretion has been proposed to be regulated by opioid receptors in
      the central nervous system (CNS). However, whether the effect of morphine is
      stimulatory or inhibitory, and the role of type specificity of opioid receptors
      have not been established. We investigated the effects of centrally injected
      opioid receptor agonists on gastric acid secretion in the perfused stomach of
      urethane-anesthetized rats. Injection of morphine (1-30 microg/rat, mu-opioid
      receptor agonist) into the fourth cerebroventricle inhibited the secretion
      stimulated by i.v. injection of 2-deoxy-D-glucose. Morphine itself did not show
      an inhibitory effect. In contrast, injection of kappa(1)-opioid receptor agonists
      such as (5alpha,7alpha,8beta)-(+)-N-methyl-N-(7-[1-pyrrolidinyl]-1
      oxaspiro[4.5]dec-8-yl)benzeneacetamide (U59593, 0.3-3 microg) and (trans)-(+/-)
      3,4-dichloro-N-methyl-N-(2-[1-pyrrolidinyl]cyclohexyl) benzeneacetamide
      hydrochloride (U50488H, 10 microg) and the kappa(2)-opioid receptor agonist,
      bremazocine (3 microg), into the lateral cerebroventricle markedly stimulated
      secretion. The effect of U59593 was inhibited by naloxone and norbinaltorphimine
      (an antagonist of kappa-opioid receptors) and in vagotomized rats. [D-Pen(2)-D
      Pen(5)]enkephalin (10microg, delta-opioid receptor agonist) had no effect on
      secretion. The dual roles of the opioid system in the CNS in gastric acid
      secretion are discussed.

PMID- 11343689
TI  - Sildenafil increases diclofenac antinociception in the formalin test.
AB  - The antinociceptive activity of an inhibitor of phosphodiesterase 5, alone or
      combined with diclofenac, was assessed in the formalin test. Local administration
      of diclofenac produced a significant antinociception in both phases of the
      formalin test in female Wistar rats. In contrast, 1-[4-ethoxy-3-(6,7-dihydro-1
      methyl-7-oxo-3-propyl-1H-pyrazolo [3,4-d]pyrimidin-5-yl)phenylsulfonyl]-4-methyl
      piperazine (sildenafil, an inhibitor of phosphodiesterase 5) produced significant
      antinociception, only during the second phase of the formalin test. Non-effective
      doses of sildenafil (25-100 microg/paw) significantly increased the
      antinociceptive effect of an inactive dose of diclofenac (25 microg) in both
      phases of the test. The antinociception produced by the drugs alone or the
      combination was due to a local action, as its administration in the contralateral
      paw was ineffective. Since sildenafil is a potent and selective inhibitor of
      phosphodiesterase 5, our results suggest that this drug produced its
      antinociceptive activity, and increased that of diclofenac, probably through the
      inhibition of cyclic GMP degradation.

PMID- 11343690
TI  - Effect of dopamine D2/D3 receptor antagonist sulpiride on amphetamine-induced
      changes in striatal extracellular dopamine.
AB  - Amphetamine increases extracellular dopamine and induces locomotor and
      stereotypical behaviors in rats. This study examined the effect of the dopamine
      D2/D3 receptor antagonist sulpiride (50 mg/kg s.c.) on the dopaminergic response
      to amphetamine (0.5, 2.0, or 8.0 mg/kg i.p.) in male Sprague-Dawley rats.
      Extracellular dopamine in the striatum was monitored using in vivo microdialysis
      and high performance liquid chromatography with electrochemical detection.
      Dopamine concentration curves were analyzed using non-linear regression and
      residual F-testing. Amphetamine enhanced extracellular dopamine in a dose
      dependent manner. Sulpiride augmented the increase in dopamine induced by 0.5 and
      2 mg/kg amphetamine by decreasing the rate of dopamine concentration fall off in
      the extracellular space (P<0.05). Sulpiride also potentiated the amount of
      dopamine increased by 8 mg/kg amphetamine, but did so by affecting the maximum
      concentration achieved (P<0.05), not the onset or offset rates. We conclude that
      the primary effect of a dopamine D2/D3 receptor antagonist is a potentiation of
      the effect of amphetamine on extracellular striatal dopamine levels, which may
      contribute to the enhanced stereotypic effects observed when paired with
      amphetamine.

PMID- 11343691
TI  - Intravenous administration of ecstasy (3,4-methylendioxymethamphetamine) enhances
      cortical and striatal acetylcholine release in vivo.
AB  - The effect of intravenous administration of 3,4-methylendioxymethamphetamine
      (MDMA), in a range of doses (0.32-3.2 mg/kg) that have been shown to maintain
      self-administration behaviour in rats, on in vivo acetylcholine release from rat
      prefrontal cortex and dorsal striatum was studied by means of microdialysis with
      vertical concentric probes. Intravenous administration of MDMA dose-dependently
      increased basal acetylcholine release from the prefrontal cortex to 57+/-21%,
      98+/-20%, 102+/-7% and 141+/-14% above baseline, at doses of 0.32, 0.64, 1.0 and
      3.2 mg/kg, respectively. MDMA also stimulated striatal acetylcholine release at
      the dose of 3.2 mg/kg i.v. (the maximal increase being 32+/-3% above baseline)
      while at the dose of 1 mg/kg i.v., MDMA failed to affect basal acetylcholine
      output. Administration of MDMA also dose-dependently stimulated behaviour. The
      results of the present study show that MDMA affects measures of central
      cholinergic neurotransmission in vivo and suggest that at least some of the
      psychomotor stimulant actions of MDMA might be positively coupled with an
      increase in prefrontal cortical and striatal acetylcholine release.

PMID- 11343692
TI  - Effects of long-term haloperidol treatment on glutamate-evoked ascorbate release
      in rat striatum.
AB  - Repeated haloperidol injections increase extracellular striatal ascorbate.
      Because ascorbate release depends on glutamate uptake, we assessed this mechanism
      in the haloperidol effect. Linear staircase voltammetry was combined with
      intrastriatal infusions of L- or D-glutamate or saline in behaving rats after 7
      or 21 days of haloperidol (0.5 mg/kg, s.c.). Control animals, receiving either
      vehicle or no treatment, responded to L-, but not D-glutamate or saline infusion
      with a 50% increase in ascorbate. In contrast, glutamate-evoked ascorbate release
      disappeared after 7 but reappeared after 21 days of haloperidol. Thus, increased
      striatal ascorbate release following chronic haloperidol cannot be explained by
      an enhanced response to glutamate.

PMID- 11343693
TI  - Deterioration of the protein kinase C-K(ATP) channel pathway in regulation of
      coronary flow in hypercholesterolaemic rabbits.
AB  - We studied the effect of experimental hypercholesterolaemia/atherosclerosis on
      changes in coronary flow and cardiac function, induced by protein kinase C and
      ATP-sensitive K(+) (K(ATP)) channel modulators in isolated Langendorff-perfused
      rabbit hearts. Both phorbol 12-myristate-13-acetate (PMA) and phorbol 12,13
      dibutyrate (PDB, 0.1 microM each), activators of protein kinase C, decreased,
      whereas staurosporine, (0.1 microM), a protein kinase C inhibitor, increased
      coronary flow and left ventricular dP/dt, an index of ventricular contractility.
      Glyburide (5-50 microM), a K(ATP) channel inhibitor, blocked the effect of
      staurosporine. The phorbol esters were without effect in the presence of
      pinacidil (5 microM), a K(ATP) channel activator. Neither the protein kinase C
      modulators nor glyburide produced any effect on coronary flow and left
      ventricular contractility, when the hearts were prepared from animals either
      maintained on a cholesterol (1.5%)-enriched diet or treated with lovastatin (5
      mg/kg/day per os). Treatment with farnesol (1 mg/kg twice a day for 7 days
      intravenously) restored the reactivity of hearts from either
      hypercholesterolaemic or lovastatin-treated animals to protein kinase C
      modulators. We conclude that non-cholesterol mevalonate products are necessary
      for the functional integrity of the protein kinase C-K(ATP) channel pathway in
      the rabbit heart.

PMID- 11343694
TI  - AG-041R, a novel indoline-2-one derivative, induces systemic cartilage
      hyperplasia in rats.
AB  - AG-041R (3R-1-(2,2-diethoxyethyl)-3-((4 methylphenyl)aminocarbonylmethyl)-3-((4
      methylphenyl) ureido)-indoline-2-one) is a novel small compound synthesized as a
      cholecystokinin-2 (CCK(2))/gastrin receptor antagonist. In the course of the
      development of this compound, we discovered unexpectedly that oral administration
      of a high dose for 4 weeks markedly induced systemic cartilage hyperplasia. This
      change was histologically observed in the auricles, the trachea, the marginal
      region of the femoral condyle, the xiphoid process and intervertebral disks in
      rats. Daily intraarticular injections of AG-041R into rat knee joints for 3 weeks
      also caused cartilage hyperplasia in the marginal region of the femoral condyle,
      but no hyperplasia was observed in any other cartilage. We have confirmed that
      chondrogenic activity of AG-041R is an intrinsic property of the compound, and is
      not due to its CCK(2)/gastrin receptor antagonistic actions. These results
      indicate that AG-041R is a novel stimulator of chondrogenesis, and can be
      expected to be a potent therapeutic agent for cartilage disorders.

PMID- 11343695
TI  - Cloricromene, a semi-synthetic coumarin derivative, inhibits tumor necrosis
      factor-alpha production at a pre-transcriptional level.
AB  - Cloricromene decreases myocardial infarct size after ischemic-reperfusion injury
      in vivo, and it has been suggested that this is due to inhibition of tumor
      necrosis factor-alpha (TNF-alpha). The purpose of this work was to characterize
      the mechanism of cloricromene-induced inhibition of TNF-alpha in rat macrophages.
      Cloricromene inhibited lipopolysaccharide-induced TNF-alpha release in a dose
      dependent manner (IC(50)=5.9 +/- 0.8 microM). This was not due to cytotoxicity,
      as cloricromene was well tolerated up to 500 microM. Cloricromene inhibited
      lipopolysaccharide-induced expression of TNF-alpha mRNA, which suggests a pre
      transcriptional effect. We then investigated the early signal transduction
      pathway triggered by lipopolysaccharide. The binding of lipopolysaccharide to its
      receptor CD14 activates protein kinase C and nuclear factor-kappaB (NF-kappaB).
      Cloricromene inhibited NF-kappaB activation in a dose-dependent manner, but
      affected protein kinase C translocation only slightly. We then established that
      cloricromene inhibited lipopolysaccharide-induced cellular oxidative activity,
      which is important for NF-kappaB activation. Our results show that cloricromene
      interferes with the early signal transduction pathway triggered by
      lipopolysaccharide.

PMID- 11343696
TI  - Nanoscale biogenic iron oxides and neurodegenerative disease.
AB  - One of the characteristics of many neurodegenerative diseases is the disruption
      of normal iron homeostasis in the brain. Recent experimental work indicates that
      nanoscale magnetic biominerals (primarily magnetite and maghemite) may be
      associated with senile plaques and tau filaments found in brain tissue affected
      by these diseases. These findings have important implications for our
      understanding of the role of iron in neurodegenerative disease as well as
      profound implications for their causes. In addition, the presence of biogenic
      magnetite in affected tissue should also provide improved mechanisms for early
      detection through the modification of MRI pulse sequences.

PMID- 11343697
TI  - A thermostable K(+)-stimulated vacuolar-type pyrophosphatase from the
      hyperthermophilic bacterium Thermotoga maritima.
AB  - Current evidence suggests the occurrence of two classes of vacuolar-type H(+)
      translocating inorganic pyrophosphatases (V-PPases): K(+)-insensitive proteins,
      identified in eukaryotes, bacteria and archaea, and K(+)-stimulated V-PPases,
      identified to date only in eukaryotes. Here, we describe the functional
      characterization of a thermostable V-PPase from the anaerobic hyperthermophilic
      bacterium Thermotoga maritima by heterologous expression in Saccharomyces
      cerevisiae. The activity of this 71-kDa membrane-embedded polypeptide has a near
      obligate requirement for K(+), like the plant V-PPase, and its thermostability
      depends on the binding of Mg(2+). Phylogenetic analysis of protein sequences
      consistently assigned the T. maritima V-PPase to the K(+)-sensitive class of V
      PPases so far only known for eukaryotes. The finding of a K(+)-stimulated V-PPase
      also in a member of a primitive eubacterial lineage strongly supports an ancient
      evolutionary origin of this group of pyrophosphate-energized proton pumps.

PMID- 11343698
TI  - Suppression of inducible cyclooxygenase and nitric oxide synthase through
      activation of peroxisome proliferator-activated receptor-gamma by flavonoids in
      mouse macrophages.
AB  - Peroxisome proliferator-activated receptor (PPAR)gamma transcription factor has
      been implicated in anti-inflammatory response. Of the compounds tested, apigenin,
      chrysin, and kaempferol significantly stimulated PPAR gamma transcriptional
      activity in a transient reporter assay. In addition, these three flavonoids
      strongly enhanced the inhibition of inducible cyclooxygenase and inducible nitric
      oxide synthase promoter activities in lipopolysaccharide-activated macrophages
      which contain the PPAR gamma expression plasmids. However, these three flavonoids
      exhibited weak PPAR gamma agonist activities in an in vitro competitive binding
      assay. Limited protease digestion of PPAR gamma suggested these three flavonoids
      produced a conformational change in PPAR gamma and the conformation differs in
      the receptor bound to BRL49653 versus these three flavonoids. These results
      suggested that these three flavonoids might act as allosteric effectors and were
      able to bind to PPAR gamma and activate it, but its binding site might be
      different from the natural ligand BRL49653.

PMID- 11343699
TI  - O-Glycosylation of G-protein-coupled receptor, octopus rhodopsin. Direct analysis
      by FAB mass spectrometry.
AB  - In addition to the N-glycan that is evidently conserved in G-protein-coupled
      receptors (GPCRs), O-glycans in the N-terminus of GPCRs have been suggested.
      Using a combination of enzymatic and manual Edman degradation in conjunction with
      G-protein coupled receptor mass spectrometry, the structure and sites of O
      glycans in octopus rhodopsin are determined. Two N-acetylgalactosamine residues
      are O-linked to Thr4 and Thr5 in the N-terminus of octopus rhodopsin. Further, we
      found chicken iodopsin, but not bovine rhodopsin, contains N-acetylgalactosamine.
      This is the first direct evidence to determine the structure and sites of O
      glycans in GPCRs.

PMID- 11343700
TI  - Gastrin-induced DNA synthesis requires p38-MAPK activation via PKC/Ca(2+) and Src
      dependent mechanisms.
AB  - We present evidence that gastrin, binding to a G protein-coupled receptor,
      activates the p38-mitogen-activated protein kinase (MAPK) pathway. Blockage of
      protein kinase C (PKC) by GF109203X, depletion of intracellular calcium by
      thapsigargin or inhibition of Src family kinases by PP2 prevented p38-MAPK
      activation and the Src kinase activity stimulated by gastrin. Inhibition of the
      PI 3-kinase by wortmannin or LY294002 did not affect these responses. In
      addition, the p38-MAPK inhibitor, SB203580, repressed gastrin-induced
      [(3)H]thymidine incorporation, indicating a major role of p38-MAPK in the growth
      promoting effect of gastrin. Our results demonstrate that gastrin-induced DNA
      synthesis requires p38-MAPK activation through mechanisms that involve calcium
      mobilization, PKC and Src family kinases.

PMID- 11343701
TI  - Bromodomain factor 1 (Bdf1) protein interacts with histones.
AB  - Using a yeast two-hybrid assay we detected an interaction between the N-terminal
      region of histone H4 (amino acids 1--59) and a fragment of the bromodomain factor
      1 protein (Bdf1p) (amino acids 304--571) that includes one of the two
      bromodomains of this protein. No interaction was observed using fragments of
      histone H4 sequence smaller than the first 59 amino acids. Recombinant Bdf1p
      (rBdf1p) demonstrates binding affinity for histones H4 and H3 but not H2A and H2B
      in vitro. Moreover, rBdf1p is able to bind histones H3 and H4 having different
      degrees of acetylation. Finally, we have not detected histone acetyltransferase
      activity associated with Bdf1p.

PMID- 11343702
TI  - Intermolecular hydrogen bonding between carotenoid and bacteriochlorophyll in
      LH2.
AB  - We have studied van der Waals contacts of the carotenoid rhodopin glucoside (RG)
      with the bacteriochlorophyll pigments absorbing at 800 nm (B800) in the crystal
      structure of Rhodopseudomonas acidophila, and the hydrogen positions were
      determined from quantum chemical calculations at the Hartree--Fock (6-31G) level.
      We have found strong evidence for hydrogen bonding between the B800 BChl and the
      RG from neighboring protomer units. The binding energy was estimated to be about
      2 kcal/mol (700 cm(-1)). CI-singles approach and time-dependent density
      functional theory calculations of the B800--RG dimer indicate a red-shift (ca 2
      nm) of the B800 Q(y) transition, along with a substantial increase of its
      oscillator strength, probably due to the hydrogen bonding.

PMID- 11343703
TI  - The 'strict' anaerobe Desulfovibrio gigas contains a membrane-bound oxygen
      reducing respiratory chain.
AB  - Sulfate-reducing bacteria are considered as strict anaerobic microorganisms, in
      spite of the fact that some strains have been shown to tolerate the transient
      presence of dioxygen. This report shows that membranes from Desulfovibrio gigas
      grown in fumarate/sulfate contain a respiratory chain fully competent to reduce
      dioxygen to water. In particular, a membrane-bound terminal oxygen reductase, of
      the cytochrome bd family, was isolated, characterized, and shown to completely
      reduce oxygen to water. This oxidase has two subunits with apparent molecular
      masses of 40 and 29 kDa. Using NADH or succinate as electron donors, the oxygen
      respiratory rates of D. gigas membranes are comparable to those of aerobic
      organisms (3.2 and 29 nmol O(2) min(-1) mg protein(-1), respectively). This
      'strict anaerobic' bacterium contains all the necessary enzymatic complexes to
      live aerobically, showing that the relationships between oxygen and anaerobes are
      much more complex than originally thought.

PMID- 11343704
TI  - Selectivity of 4,5,6,7-tetrabromobenzotriazole, an ATP site-directed inhibitor of
      protein kinase CK2 ('casein kinase-2').
AB  - The specificity of 4,5,6,7-tetrabromo-2-azabenzimidazole (TBB), an ATP/GTP
      competitive inhibitor of protein kinase casein kinase-2 (CK2), has been examined
      against a panel of 33 protein kinases, either Ser/Thr- or Tyr-specific. In the
      presence of 10 microM TBB (and 100 microM ATP) only CK2 was drastically inhibited
      (>85%) whereas three kinases (phosphorylase kinase, glycogen synthase kinase 3
      beta and cyclin-dependent kinase 2/cyclin A) underwent moderate inhibition, with
      IC(50) values one--two orders of magnitude higher than CK2 (IC(50)=0.9 microM).
      TBB also inhibits endogenous CK2 in cultured Jurkat cells. A CK2 mutant in which
      Val66 has been replaced by alanine is much less susceptible to inhibition by TBB
      as well as by another ATP competitive inhibitor, emodin. These data show that TBB
      is a quite selective inhibitor of CK2, that can be used in cell-based assays.

PMID- 11343705
TI  - Conformational states of annexin VI in solution induced by acidic pH.
AB  - Acidic pH-induced folding of annexin (Anx)VI in solution was investigated in
      order to study the mechanism of formation of ion channels by the protein in
      membranes. Using 2-(p-toluidino)naphthalene-6-sulfonic acid as a hydrophobic
      probe, it was demonstrated that AnxVI exerts a large change in hydrophobicity at
      acidic pH. Moreover, circular dichroism spectra indicated that the native state
      of AnxVI changes at acidic pH towards a state characterized by a significant loss
      of alpha-helix content and appearance of new beta-structures. These changes are
      reversible upon an increase of pH. It is postulated that the structural folding
      of AnxVI could explain how a soluble protein may undergo transition into a
      molecule able to penetrate the membrane hydrophobic region. The physiological
      significance of these observations is discussed.

PMID- 11343706
TI  - Involvement of FAK/Src complex in the processes of Escherichia coli phagocytosis
      by insect hemocytes.
AB  - Recently we demonstrated that lipopolysaccharide promotes activation of the
      Ras/mitogen-activated protein cascade in hemocytes and that phagocytosis of
      Escherichia coli by insect hemocytes is mediated by an integrin-dependent process
      [Foukas et al. (1998) J. Biol. Chem. 273, 14813--14818]. Here we report data
      concerning the focal adhesion kinase (FAK) tyrosine phosphorylation status in
      hemocytes in response to E. coli. We demonstrate that E. coli-triggering
      stimulates a significant increase in tyrosine phosphorylation of FAK in
      hemocytes. Furthermore, immunoblotting analysis using anti-Y397 demonstrated
      intense FAK activity at the Y397/SH2-binding site in hemocytes treated with E.
      coli. In addition, antibody-mediated inhibition of FAK and Src-kinase has been
      shown to abolish FAK phosphorylation and E. coli phagocytosis, indicating a
      specific role for the FAK/Src complex in the processes of promoting cell
      phagocytosis. These findings expand the known signaling functions of FAK and
      provide insight into signal transduction events associated with hemocyte
      phagocytosis in response to E. coli.

PMID- 11343709
TI  - Effect of patch size and in-patch location on the infaunal macroinvertebrate
      assemblages of Zostera marina seagrass beds.
AB  - Much recent work on patch-occupancy dynamics has been concentrated in terrestrial
      ecosystems, with few examples evident from soft-sediment marine habitats.
      Seagrass landscapes have recently been recognised to be potentially ideal marine
      models for the study of such ecological concepts. Infaunal macroinvertebrate
      assemblages of two patch sizes of the seagrass Zostera marina were compared:
      small (<15 m diameter) and large (>30 m diameter), using an unreplicated random
      block design. Further comparison was made between infaunal assemblage composition
      at the edge and centre of each patch. Univariate statistical analysis of data
      indicated significantly greater total numbers of taxa in samples from large
      patches than in small. Multivariate analyses indicated significant differences in
      assemblage composition due to both patch size and in-patch location, and revealed
      that differences were due to small changes in the relative abundances of many
      taxa. Possible mechanisms underlying the observed variations of assemblage
      composition with patch size and in-patch location are discussed. Although the
      present results support some of the theories relating to the control of infaunal
      assemblage composition, explanations are not applicable across all taxonomic
      groups. At the scale of the present study, seagrass patch size and edge-effects
      appear to be less significant than 'regional' factors, which relate to relatively
      small variation in environmental parameters, for the structuring of infaunal
      macroinvertebrate assemblages.

PMID- 11343710
TI  - Comparative biochemical composition in gonad and adductor muscle of triploid and
      diploid catarina scallop (Argopecten ventricosus Sowerby II, 1842).
AB  - Biochemical components of gonad and adductor muscle for diploid and triploid
      catarina scallop, Argopecten ventricosus, were evaluated and compared at four
      periods in 1 year (January, April, June, and October). Two comparisons were done.
      The first one compared an untreated control (diploid) vs. a triploidy-treated
      group for which the percentage of triploids was 57%. The second comparison was
      done on a group derived from within the triploidy-treated group, separating
      diploids (internal control) from triploids ('putative triploids'). Regardless of
      which comparison, in the gonad diploid scallops had larger concentrations of
      proteins, carbohydrates, lipids, and acylglycerols than triploid scallops. This
      reflects the maturation processes in diploid scallops vs. the sterility seen in
      most triploid scallops, and it is particularly supported by the consistently
      larger concentration of acylglycerols in gonads of diploids than in triploids.
      The gonad index of the internal control (diploid) group was significantly larger
      than that seen in the putative triploid group at all sampling periods but
      October, when none of the gonad biochemical components were different between
      ploidy groups.Triploid scallops had a significantly larger muscle index than
      diploids from April to October. This can be caused by a larger gain in muscle
      tissue in triploids than diploids from January to June. However, there were no
      consistent differences in any of the biochemical components evaluated in adductor
      muscle of diploids and triploids. The use of freshly ingested food rather than
      reserve mobilization from muscle in diploids is suggested by these results.
      Nutrients derived from ingested food are apparently used for muscle growth in
      triploids, whereas in diploids those nutrients serve primarily for gonad
      development. The importance of freshly ingested food for maintenance and growth
      is suggested because the decline in biochemical components seen in October in
      both muscle and gonad was paired with a decline in weight of those two organs,
      especially when the control groups are considered, but a decrease was also
      evident for the triploid groups. This may have been caused by the presence of El
      Nino, with its characteristic high water temperatures and low productivity.

PMID- 11343707
TI  - Phosphorylation of murine homeodomain protein Dlx3 by protein kinase C.
AB  - The Dlx3 homeodomain gene is expressed in terminally differentiated murine
      epidermal cells. As demonstrated for differentiation-specific granular markers,
      Dlx3 is activated in primary mouse keratinocytes cultured in vitro by increasing
      the level of the extracellular Ca(2+). This activation is mediated through a
      protein kinase C-dependent (PKC) pathway. In this study, we investigated whether
      PKC can modulate the activity of murine Dlx3 protein. Using in vitro kinase
      assays, we show that PKC enzymes phosphorylate the Dlx3 protein. Using
      keratinocyte nuclear extracts for the kinase reaction, we determined that Dlx3
      protein is phosphorylated, and the phosphorylation is inhibited by the PKC
      specific inhibitor GF109203X, suggesting that Dlx3 is phosphorylated by PKC in
      vivo. Of the PKC isoforms present in the epidermis, we tested alpha, delta,
      epsilon and zeta. Dlx3 is primarily phosphorylated by PKC alpha. By deletion and
      mutational analysis, we show that the serine residue S(138), located in the
      homeodomain of Dlx3 protein, was specifically phosphorylated by PKC. The
      phosphorylation of purified Dlx3 proteins by PKC partially inhibited formation of
      complexes between Dlx3 protein and DNA. These results suggest that Dlx3 protein
      can be directly phosphorylated by PKC and this affects the DNA binding activity
      of Dlx3.

PMID- 11343711
TI  - Acinar primary cell culture from the digestive gland of Pecten maximus (L.): an
      original model for ecotoxicological purposes.
AB  - The purpose of this study was to establish an original primary acinar cell
      culture model for the mollusc bivalve Pecten maximus (L.), and to define its
      values and limits for subsequent ecotoxicological applications. To prevent
      microbial contaminations occurring frequently in invertebrate cell cultures, a
      perfusion of the stomach-digestive gland complex was performed in situ using a
      sterile salt solution containing broad-range antibiotics. Digestive acini were
      isolated using a pronase enzyme that was removed by several washings of the
      acinar suspension, after which their viability and functionality were determined
      by three different assays: fluorescein diacetate (FDA) de-esterification, 3-4,5
      dimethylthiazol-2-yl-2,5-diphenyl tetrazolium (MTT) reduction and neutral red
      (NR) incorporation describing de-esterification, mitochondrial dehydrogenase and
      lysosome activity, respectively. The kinetic conditions for these assays were
      defined beforehand. The results showed that digestive acini could be maintained
      in vitro both cytologically and functionally for at least 96 h, which is
      sufficient for many ecotoxicological applications. Preliminary contamination
      assays, according to the function studied (cell esterases, mitochondrial
      respiration, lysosomal incorporation), indicated that polycyclic aromatic
      hydrocarbons had a negative effect on the survival of acini in vitro.

PMID- 11343712
TI  - A molecular biomarker system for assessing the health of gastropods (Ilyanassa
      obsoleta) exposed to natural and anthropogenic stressors.
AB  - We developed a Molecular Biomarker System (MBS) to assess the physiological
      status of mud snails (Ilyanassa obsoleta) challenged by exposure to high
      temperature, cadmium, atrazine, endosulfan and the water-accommodating fraction
      of bunker fuel #2. The MBS is used to assay specific cellular parameters of the
      gastropod cell that are indicative of a non-stressed or stressed condition. The
      MBS distinguished among responses to each stressor and to non-stressed control
      conditions. For example, the biomarkers metallothionein and cytochrome P450 2E1
      homologue distinguished between metal and non-metal stresses. MBS data from this
      study corroborate toxicological studies of organismal responses to endosulfan,
      atrazine, fuel and cadmium stresses. The MBS technology aids in the accurate
      diagnosis of the snail's health condition because the physiological significance
      of the changes of each biomarker is well known. This technology is particularly
      relevant for environmental monitoring because gastropods are used as key
      indicator species in many estuarine, marine, freshwater and terrestrial
      ecosystems. Finally, the Molecular Biomarker System technology is relatively
      inexpensive, easy to implement, precise and can be quickly adapted to an
      automated, high-throughput system for large sample analysis.

PMID- 11343713
TI  - Physiological stress in decapod crustaceans (Munida rugosa and Liocarcinus
      depurator) discarded in the Clyde Nephrops fishery.
AB  - Crustacean discards experience stress during commercial fishing operations, due
      to increased exercise while in the trawl and aerial exposure during sorting of
      the catch. Physiological stress and recovery were assessed following trawling of
      two ecologically important decapod species, regularly discarded in the Clyde
      Nephrops fishery. Haemolymph samples taken from trawled swimming crabs,
      Liocarcinus depurator, and squat lobsters, Munida rugosa, had significantly
      higher concentrations of ammonia (0.308 and 0.519 mmol l(-1)), D-glucose (0.14
      and 0.097 mmol l(-1)) and L-lactate (6.2 and 0.87 mmol l(-1)) compared with
      controls, indicating an impairment of ammonia excretion and a switch to anaerobic
      metabolism. Concurrently, the haemolymph pH of trawled squat lobsters was low
      (7.47) compared with controls (7.75); however, the reverse trend was found in L.
      depurator. Initially elevated lactate (7.98 mmol l(-1)) and glucose (0.73 mmol l(
      1)) concentrations of trawled and emersed (1 h) L. depurator were restored, 4 h
      after re-immersion along with pH (7.54). Crabs that had been emersed for 1 h had
      significantly higher concentrations of glucose (0.2 mmol l(-1)) and lactate (5.14
      mmol l(-1)), and had more acidic blood (7.64) than L. depurator subject to 1 h of
      exercise, indicating that anoxia was the main cause of physiological stress.
      Crabs and squat lobsters lost 7% and 9% of their initial body wet weight
      following 1 h of emersion, although blood osmolarities did not change
      significantly. While all animals survived aerial exposure in our experiments,
      sorting of the catch on commercial boats takes up to 300 min, which could lead to
      mortality or sub-lethal chronic biochemical changes that could compromise
      fitness.

PMID- 11343714
TI  - Thermal compensation of metabolism in the temperate coral, Plesiastrea versipora
      (Lamarck, 1816).
AB  - Plesiastrea versipora is a hermatypic coral with a distribution that extends to
      the southern limit for hermatypic corals. The normal annual temperature range for
      this coral in Port Phillip Bay (Victoria) (approximately 10-21 degrees C) is well
      below the physiological optimum for the majority of hermatypic corals (25-29
      degrees C). The rate of photosynthesis and respiration in Plesiastrea generally
      increased with temperature before levelling out at the higher temperatures, with
      Q(10) data suggesting that both photosynthesis and respiration in Plesiastrea
      acclimate to changing temperatures. Respiration showed a similar trend to
      photosynthesis, with respect to temperature, but with a slightly lower rate of
      increase. Photosynthetic rate in Plesiastrea is comparable with that of reef
      corals despite lower temperatures and irradiance. When expressed as a function of
      chlorophyll a content photosynthesis approached perfect temperature compensation
      with prolonged exposure to various temperatures. Temperature-dependent changes
      with chlorophyll content may be responsible for temperature related changes in
      photosynthetic rate. This may be a mechanism for stabilising the symbiotic
      relationship over a wide temperature range. Autotrophic ability, estimated from
      photosynthesis/respiration (P/R) ratios, was greatest at higher temperatures and
      was only slightly less than that of reef corals. At low temperatures Plesiastrea
      may be dependent on heterotrophic feeding.

PMID- 11343715
TI  - Response of a scleractinian coral, Stylophora pistillata, to iron and nitrate
      enrichment.
AB  - The purpose of this study was to determine whether the addition of iron alone or
      in combination with nitrate affects growth and photosynthesis of the
      scleractinian coral, Stylophora pistillata, and its symbiotic dinoflagellates.
      For this purpose, we used three series of two tanks for a 3-week enrichment with
      iron (Fe), nitrate (N) and nitrate+iron (NFe). Two other tanks were kept as a
      control (C). Stock solutions of FeCl(3) and NaNO(3) were diluted to final
      concentrations of 6 nM Fe and 2 &mgr;M N and continuously pumped from batch tanks
      into the experimental tanks with a peristaltic pump. Results obtained showed that
      iron addition induced a significant increase in the areal density of
      zooxanthellae (ANOVA, p=0.0013; change from 6.3+/-0.7x10(5) in the control to
      8.5+/-0.6x10(5) with iron). Maximal gross photosynthetic rates normalized per
      surface area also significantly increased following iron enrichment (ANOVA,
      p=0.02; change from 1.23+/-0.08 for the control colonies to 1.81+/-0.24 &mgr;mol
      O(2) cm(-2) h(-1) for the iron-enriched colonies). There was, however, no
      significant difference in the photosynthesis normalized on a per cell basis.
      Nitrate enrichment alone (2 &mgr;M) did not significantly change the
      zooxanthellae density or the rates of photosynthesis. Nutrient addition (both
      iron and nitrogen) increased the cell-specific density of the algae (CSD)
      compared to the control (G-test, p=0.3x10(-9)), with an increase in the number of
      doublets and triplets. CSD was equal to 1.70+/-0.04 in the Fe-enriched colonies,
      1.54+/-0.12 in the N- and NFe-enriched colonies and 1.37+/-0.02 in the control.
      Growth rates measured after 3 weeks in colonies enriched with Fe, N and NFe were
      23%, 34% and 40% lower than those obtained in control colonies (ANOVA, p=0.011).

PMID- 11343716
TI  - Effect of size of attended area on contrast sensitivity function.
AB  - Contrast sensitivity functions (CSFs) were measured in the foveal region while
      subjects simultaneously performed an instantaneous judgment task, which was
      designed to maintain their attended areas at a constant size. Spatial attention
      was sustained over areas that were either narrow (Narrow condition) or broad
      (Broad condition). We observed that the sensitivity at higher frequencies (over 3
      cpd) was greater under the Narrow condition than that under the Broad condition,
      supporting the argument that attention enhances spatial resolution.

PMID- 11343717
TI  - Photographic reproduction of out-of-focus and distorted ocular imagery.
AB  - The necessary settings and parameters were determined for ordinary camera and
      lens systems to faithfully reproduce out-of-focus and distorted imagery as it
      falls upon the retina of the human eye. Theoretic considerations of both
      geometric and physical optics were used to calculate the "relative blur" and
      distortion produced by refractive error added to ordinary camera lenses as
      opposed to refractive error in an arbitrary thick-lens optical system bounded by
      air and fluid (i.e. the eye). In both the camera and the eye, "relative blur" was
      determined to be directly proportional to dioptric defocus and to aperture size,
      and effectively independent of the focal length. Distortion of imagery was also
      found to be independent of the focal length. Photographs corroborate the
      theoretic findings. A given amount of relative blur, however, appeared somewhat
      greater when recorded on photographic film than when appreciated by the human
      eye. The Stiles-Crawford effect, the chromatic aberration of the eye, and neural
      processing probably each contribute to this difference. Previous investigators
      have grossly exaggerated blur and distortion in photographs intended to simulate
      ocular imagery and have drawn misleading conclusions from their results.

PMID- 11343718
TI  - Effects of set-size and selective spatial attention on motion processing.
AB  - In order to investigate the effects of divided attention and selective spatial
      attention on motion processing, we obtained direction-of-motion thresholds using
      a stochastic motion display under various attentional manipulations and stimulus
      durations (100-600 ms). To investigate divided attention, we compared motion
      thresholds obtained when a single motion stimulus was presented in the visual
      field (set-size=1) to those obtained when the motion stimulus was presented
      amongst three confusable noise distractors (set-size=4). The magnitude of the
      observed detriment in performance with an increase in set-size from 1 to 4 could
      be accounted for by a simple decision model based on signal detection theory,
      which assumes that attentional resources are not limited in capacity. To
      investigate selective attention, we compared motion thresholds obtained when a
      valid pre-cue alerted the subject to the location of the to-be-presented motion
      stimulus to those obtained when no pre-cue was provided. As expected, the effect
      of pre-cueing was large when the visual field contained noise distractors, an
      effect we attribute to "noise reduction" (i.e. the pre-cue allows subjects to
      exclude irrelevant distractors that would otherwise impair performance). In the
      single motion stimulus display, we found a significant benefit of pre-cueing only
      at short durations (< or =150 ms), a result that can potentially be explained by
      a "time-to-orient" hypothesis (i.e. the pre-cue improves performance by
      eliminating the time it takes to orient attention to a peripheral stimulus at its
      onset, thereby increasing the time spent processing the stimulus). Thus, our
      results suggest that the visual motion system can analyze several stimuli
      simultaneously without limitations on sensory processing per se, and that spatial
      pre-cueing serves to reduce the effects of distractors and perhaps increase the
      effective processing time of the stimulus.

PMID- 11343719
TI  - Information limitations in perception of shape from texture.
AB  - Li and Zaidi (Li, A., and Zaidi, Q. (2000) Vision Research, 40, 217-242) showed
      that the veridical perception of the 3-dimensional (3D) shape of a corrugated
      surface from texture cues is entirely dependent on the visibility of critical
      patterns of oriented energy. These patterns are created by perspective projection
      of surface markings oriented along lines of maximum 3D curvature. In images
      missing these orientation modulations, observers confused concavities with
      convexities, and leftward slants with rightward slants. In this paper, it is
      shown that these results were a direct consequence of the physical information
      conveyed by different oriented components of the texture pattern. For texture
      patterns consisting of single gratings of arbitrary spatial frequency and
      orientation, equations are derived from perspective geometry that describe the
      local spatial frequency and orientation for any slant at any height above and
      below eye level. The analysis shows that only gratings oriented within a few
      degrees of the axis of maximum curvature exhibit distinct patterns of orientation
      modulations for convex, concave, and leftward and rightward slanted portions of a
      corrugated surface. All other gratings exhibit patterns of frequency and
      orientation modulations that are distinct for curvatures on the one hand and
      slants on the other, but that are nearly identical for curvatures of different
      sign, and nearly identical for slants of different direction. The perceived shape
      of surfaces was measured in a 5AFC paradigm (concave, convex, leftward slant,
      rightward slant, and flat-frontoparallel). Observers perceived all five shapes
      correctly only for gratings oriented within a few degrees of the axis of maximum
      curvature. For all other oriented gratings, observers could distinguish
      curvatures from slants, but could not distinguish signs of curvature or
      directions of slant. These results demonstrate that human observers utilize the
      shape information provided by texture components along both critical and non
      critical orientations.

PMID- 11343720
TI  - Nonlocal interactions in color perception: nonlinear processing of chromatic
      signals from remote inducers.
AB  - The perceived color of an object depends on the chromaticity of its immediate
      background. But color appearance is also influenced by remote chromaticities. To
      quantify these influences, the effects of remote color fields on the appearance
      of a fixated 2 degrees test field were measured using a forced-choice method.
      Changes in the appearance of the test field were induced by chromaticity changes
      of the background and of 2 degrees color fields not adjacent to the test field.
      The appearance changes induced by the color of the background corresponded to a
      fraction of between 0.5 and 0.95 of the cone contrast of the background change,
      depending on the observer. The magnitude of induction by the background color was
      modulated on average by 7.6% by chromaticity changes in the remote color fields.
      Chromaticity changes in the remote fields had virtually no inducing effect when
      they occurred without a change in background color. The spatial range of these
      chromatic interactions extended over at least 10 degrees from the fovea. They
      were established within the first few hundred milliseconds after the change of
      background color and depended only weakly on the number of inducing fields. These
      results may be interpreted as reflecting rapid chromatic interactions that
      support robustness of color vision under changing viewing conditions.

PMID- 11343721
TI  - Energy model for contrast detection: spatial-frequency and orientation
      selectivity in grating summation.
AB  - Models of spatial vision usually assume a "front-end" of spatial-frequency and
      orientation selective channels. Subthreshold-summation studies have provided some
      of the strongest support for this notion. We applied a single-channel energy
      model and a multiple-channels probability-summation model to explore subthreshold
      summation phenomena. We measured the contrast thresholds for detection of two
      superimposed Gabor patches as a function of the spatial-frequency and orientation
      difference between the components. The stimuli were centred 7.5 deg above the
      fixation point and were windowed by a Gaussian function with one of two different
      spatial spreads. We have shown that the spatial-frequency and orientation
      selectivity in subthreshold summation of Gabor patches is determined by the
      similarity (cross-correlation) between the stimulus components. A single-channel
      energy model as well as a multiple-channels probability-summation model could
      explain the summation data.

PMID- 11343722
TI  - A model of eye movements and visual working memory during problem solving in
      geometry.
AB  - The Oculomotor Geometry Reasoning Engine (OGRE) was proposed to model eye
      movements and visual working memory during problem solving in geometry. OGRE
      postulates that geometrical elements from diagrams are added to visual working
      memory when they are scanned. Newly-added elements overwrite elements already in
      memory. The model was applied to eye-movement patterns of three subjects: two
      geometry experts and one non-expert. Their eye movements and verbal protocols
      were recorded as they solved geometry problems posed with diagrams. Subjects used
      highly redundant eye-movement patterns with multiple rescans of the same
      geometrical elements. OGRE's model of visual memory provided a good fit for the
      distribution of times between rescans. The model was used to estimate the size of
      visual working memory used in geometry. The estimates varied as a function of
      both problems and subjects, with means and standard deviations for each subject
      being: 5.3+/-1.4, 4.0+/-0.9 and 4.7+/-1.6.

PMID- 11343723
TI  - A model of visual-spatial memory across saccades.
AB  - This paper describes a neural network model that directs saccades back to targets
      after they disappear and other saccades intervene. This is a simple example of
      knowing where something is after it is no longer visible and the observer has
      moved. These tasks require a short-term memory that can store continuous values
      of spatial location. The model was generated by training a neural network with a
      recurrently connected hidden layer to specify memory-guided saccades. The trained
      network maintains stored locations accurately for a few seconds. It uses a leaky
      integrator mechanism in which there is a slow decay of the stored value to a
      small number of fixed point attractors. Similar mechanisms have been used to
      model oculomotor integration (Cannon, S., Robinson, D., & Shamma, S. (1983). A
      proposed neural network for the integrator of the oculomotor system. Biological
      Cybernetics, 49, 127-136; Seung, H. (1998). Continuous attractors and oculomotor
      control. Neural Networks, 11, 1253-1258). The mechanism is robust to parameters
      such as the input and output format and the constraints in training. However, the
      receptive field properties of the hidden units do depend on these parameters. It
      was possible to find biologically plausible parameters that produced hidden unit
      behavior similar to that of real neurons involved in saccade memory. In
      particular, training the model to simultaneously represent the target location in
      both eye- and head-based reference frames produces units similar to neurons in
      parietal saccade areas.

PMID- 11343724
TI  - Clinical suppression in monkeys reared with abnormal binocular visual experience.
AB  - To determine if monkeys exhibit clinical suppression in response to early
      abnormal binocular vision, we compared dichoptic to monocular luminance increment
      thresholds in monkeys reared with alternating monocular defocus or optically
      induced strabismus. In the absence of amblyopia, clinical suppression was
      associated with strabismus and with as little as 1.50 diopters of anisometropia.
      The severity of suppression was roughly correlated with the magnitude of
      anisometropia. The demonstration of clinical suppression in monkeys provides a
      model for future investigations of factors that may influence the development of
      suppression, but which are not possible to accurately document or manipulate in
      human subjects.

PMID- 11343727
TI  - South Africa's moral victory.

PMID- 11343728
TI  - Window of opportunity for pain control in the terminally ill.

PMID- 11343729
TI  - Radicalism in therapy of lung cancer.

PMID- 11343730
TI  - Effective antibiotic-resistance control strategies.

PMID- 11343731
TI  - Bedside treatment of chronic subdural haematoma?

PMID- 11343732
TI  - Vesicoureteric reflux: to operate or not?

PMID- 11343733
TI  - Resuscitating dead languages.

PMID- 11343734
TI  - Understanding the experience of pain in terminally ill patients.
AB  - BACKGROUND: Terminally ill patients commonly experience substantial pain.
      Unresolved pain has been cited as evidence that end-of-life care is of poor
      quality. However, the data on which that conclusion is based are limited. We
      aimed to provide additional data on the experience of pain in such patients.
      METHODS: We interviewed 988 terminally ill patients from six randomly selected US
      sites. We asked them who had treated their pain in the previous 4 weeks (primary
      care physician, pain specialist, or both), and whether they wanted more pain
      medication than they were receiving, or why they did not want more. FINDINGS: 496
      (50%) terminally ill patients reported moderate or severe pain. 514 (52%)
      individuals had seen a primary-care physician for treatment of pain in the
      previous 4 weeks and 198 (20%) saw a pain specialist. Of those who had been
      treated by their primary-care physician, 287 (29%) wanted more therapy, 613 (62%)
      wanted their pain therapy to remain the same, and 89 (9%) wanted to reduce or
      stop their pain therapy. Several reasons for not wanting additional therapy were
      offered-fear of addiction, dislike of mental or physical side-effects, and not
      wanting to take more pills or injections. We saw no association between disease
      and amount of pain between disease and the desire for more treatment. Black
      patients were more likely to seek additional pain therapy, see a pain specialist,
      and refuse additional medication because of fear of addiction than other
      populations. INTERPRETATION: Although half of terminally ill patients experienced
      moderate to severe pain, only 30% of them wanted additional pain treatment from
      their primary-care physician. The number of patients experiencing pain remains
      too high. However, the number is not as large as perceived. Additionally, most
      are willing to tolerate pain. Furthermore, the experience of pain is constant
      across major terminal diseases.

PMID- 11343735
TI  - Epilepsy control with phenobarbital or phenytoin in rural south India: the
      Yelandur study.
AB  - BACKGROUND: Epilepsy is a controllable disorder if detected and treated early.
      For most families in rural areas of less developed countries, however, treatment
      can be delayed because of the inaccessibility of specialist neurological
      assessment facilities. We aimed to find a practical solution to rural epilepsy
      control by doing a non-randomised trial in south India. METHODS: 135 patients
      with partial or generalised tonic-clonic seizures agreed to long-term treatment
      with phenobarbital (n=68), phenytoin (n=60), or both (n=7). Drugs were given once
      daily, and at the lowest effective dose, by trained primary-care physicians and
      health workers. All management was entirely clinical. The main outcome measure
      was absence of seizures of any type for at least 2 years (terminal remission).
      Analysis was by intention to treat. FINDINGS: The proportion with terminal
      remission at each of 4 successive years of follow-up ranged from 58% to 66% for
      patients who were drug compliant and who had a lifetime total of 30 or fewer
      generalised tonic-clonic seizures. The corresponding range for patients who were
      not compliant and who had ever had more than 30 such seizures was 6-16%.
      Multivariate logistic regression analysis confirmed that strict drug compliance
      and early treatment were important predictors of a 2-year terminal remission.
      Clinical adverse effects were noted in three (4%) patients on phenobarbital and
      67 (43%) of those on phenytoin (mainly in the form of gingival hyperplasia).
      INTERPRETATION: In rural areas of less developed countries, epilepsy control in
      its early stages can be practical and effective with existing resources. The key
      to success is a combination of trained primary-care physicians, health workers,
      inexpensive phenobarbital, drug compliance, health education, and follow-up.

PMID- 11343736
TI  - Clinical Picture: Muscle lymphoma.

PMID- 11343737
TI  - Effect of ACE inhibitors on angiographic restenosis after coronary stenting
      (PARIS): a randomised, double-blind, placebo-controlled trial.
AB  - BACKGROUND: The DD genotype for the angiotensin-I converting enzyme (ACE I)
      deletion allele (D) polymorphism is a possible genetic risk factor for restenosis
      after coronary stent implantation. We aimed to establish whether or not blockade
      of ACE with high doses of ACE inhibitors could reduce this risk of angiographic
      restenosis. METHODS: We characterised the ACE I/D polymorphism in 345 consecutive
      patients who were undergoing coronary stenting. 115 had the DD genotype. We
      assigned 91 of these 115 patients to quinapril 40 mg daily (n=46) or placebo
      (n=45). Treatment was started within 48 h after stent implantation and continued
      for 6 months. 79 patients complied with the protocol and underwent follow-up
      angiography after 6 months. FINDINGS: Our primary endpoint of late loss in
      minimum lumen diameter (a quantitative index of restenosis) was significantly
      higher in the quinapril group than in the controls (mean 1.11 mm [SD 0.70] vs
      0.76 mm [0.60]; p=0.018). Secondary endpoints also showed consistent trends
      towards increased angiographic restenosis in the treatment group. INTERPRETATION:
      Contrary to our expectations, ACE inhibitor treatment did not reduce restenosis
      after coronary stent implantation in patients with DD genotype, but was
      associated with an exaggerated restenotic process when compared with
      administration of placebo.

PMID- 11343738
TI  - Persistence of sulphonamide resistance in Escherichia coli in the UK despite
      national prescribing restriction.
AB  - BACKGROUND: There is a clear association between heavy antimicrobial consumption
      within a population and the frequent recovery of resistant bacteria, but whether
      a reduction in antimicrobial use can reverse this process is less clear. We
      investigated the effect of a national restriction of sulphonamide prescribing in
      the UK on the prevalence of sulphonamide resistance in Escherichia coli. METHODS:
      Consecutive clinical isolates of E coli were collected at the Royal London
      Hospital in 1991 and 1999. These collections, each of more than 350 isolates,
      were compared. Minimum inhibitory concentrations of sulphamethoxazole and eight
      other antimicrobials were determined. The presence and locations of sulphonamide
      resistance genes were examined by PCR, plasmid extraction, Southern
      hybridisation, and transconjugation. FINDINGS: Despite a huge decrease in
      sulphonamide prescriptions (from 3,208,000 [corrected] prescriptions per year in
      1991 to 77,000 [corrected] in 1999), the frequency of resistance remained high in
      1999 (165/359 [46.0%] vs 143/360 [39.7%] in 1991; difference 6.2% [95% CI 20.9 to
      13.3]). Integron-borne sulI was present in 16.4% of isolates in 1991 and 17.5% in
      1999. The prevalence of sulII increased from 26.7% in 1991 to 36.5% in 1999
      (difference 9.8% [3.1 to 16.5] p=0.0046). SulII was located on large plasmids, at
      least some of which were conjugative multiresistance determinants.
      INTERPRETATION: These results show that a huge decrease in antibiotic prescribing
      does not necessarily reduce resistance within a useful time. The main reason
      seems to be the genetic linkage of the index resistance to other resistance
      determinants.

PMID- 11343739
TI  - Medical versus surgical treatment in children with severe bilateral
      vesicoureteric reflux and bilateral nephropathy: a randomised trial.
AB  - BACKGROUND: Nephropathy associated with vesicoureteric reflux (VUR) and urinary
      tract infection can result in end-stage renal failure, hypertension, or both.
      Whether long-term VUR contributes to these outcomes is unknown. We compared, in a
      randomised trial, medical with surgical management of children with bilateral
      severe VUR and bilateral nephropathy. METHODS: We stratified by age and
      glomerular filtration rate (GFR) 25 boys and 27 girls aged 1-12 years and
      randomly assigned them to medical or surgical management. At enrolment and 4
      years' follow-up we estimated GFR from the plasma clearance of 51Cr-labelled
      edetic acid (EDTA), and did intravenous urography. We also did a metastable 99mTc
      labelled dimercaptosuccinic acid (DMSA) assay and contrast cystography. The
      change in GFR at 4 years, expressed as a percentage change between enrolment and
      4 years, was available for 26 of 27 patients in the medical and 24 of 25 in the
      surgical group. We assessed GFR in 48 patients 10 years after enrolment.
      FINDINGS: Mean GFR at enrolment was 72.4 mL/min per 1.73 m(2) (SD 24.1) in the
      medical and 71.7 mL/min per 1.73 m(2) (22.6) in the surgical group. The mean
      percentage change in GFR at 4 years was 2.4% (SE 4.5) versus 4.7% (5.0) in the
      medical and surgical groups, respectively. The difference in change in GFR at 4
      years between the two groups was not significant (7.1%, 95% CI 6.4% to 20.6%).
      INTERPRETATION: Our data do not lend support to the view that the outcome for
      renal function is improved by surgical correction of VUR in children with
      bilateral disease.

PMID- 11343740
TI  - An abnormal venous clot.

PMID- 11343741
TI  - Detection of breast cancer cells in ductal lavage fluid by methylation-specific
      PCR.
AB  - If detected early, breast cancer is curable. We tested cells collected from the
      breast ducts by methylation-specific PCR (MSP). Methylated alleles of Cyclin D2,
      RAR-beta, and Twist genes were frequently detected in fluid from mammary ducts
      containing endoscopically visualised carcinomas (17 cases of 20), and ductal
      carcinoma in situ (two of seven), but rarely in ductal lavage fluid from healthy
      ducts (five of 45). Two of the women with healthy mammograms whose ductal lavage
      fluid contained methylated markers and cytologically abnormal cells were
      subsequently diagnosed with breast cancer. Carrying out MSP in these fluid
      samples may provide a sensitive and powerful addition to mammographic screening
      for early detection of breast cancer.

PMID- 11343742
TI  - MUC 1: a genetic susceptibility to infertility?
AB  - In man and some animals regulation of embryo implantation by endometrial
      expression of the highly polymorphic MUC 1 mucin has been suggested. We assessed
      the polymorphism of MUC 1 in women known to be fertile and those with infertility
      due to suspected failure of embryo implantation. The median of the lower allele
      size in the infertile group was only 2.5 kb compared with 3.4 kb in the fertile
      group (p=0.0029, difference 0.9, [95% CI 0.1-1.3]). Women with unexplained
      infertility might have a genetic susceptibility to failure of embryo implantation
      due to small MUC 1 allele size.

PMID- 11343743
TI  - Vanilloid receptor 1 immunoreactivity in inflamed human bowel.
AB  - Vanilloid receptor 1 (VR1) is expressed by sensory neurons. Once activated, these
      neurons evoke the sensation of burning pain and release neuropeptides that induce
      neurogenic inflammation. We used immunoblotting and immunostaining to estimate
      the density of VR1 in colonic tissues of patients with inflammatory bowel disease
      and of controls. Our study results indicate that VR1 immunoreactivity is greatly
      increased in colonic nerve fibres of patients with active inflammatory bowel
      disease. Thus, the discovery of new drugs that can bind the VR1 receptor, or
      antagonise endogenous inflammatory substances that activate this receptor, could
      lead to new therapies for pain and dysmotility.

PMID- 11343744
TI  - Variant Creutzfeldt-Jakob disease in an elderly patient.
AB  - We report a case of variant Creutzfeldt-Jakob disease(vCJD) in a 74-year old man
      in whom diagnosis was made at necropsy. The occurrence of vCJD in an individual
      in this age group is unlikely to be an isolated event. Doctors need to be aware
      that vCJD can arise in elderly patients so that appropriate investigations
      (including magnetic resonance imaging) can be done, and permission for
      neuropathological necropsy requested, in suspected cases. This case could also
      have important implications for public health policy decisions and surveillance
      programmes that target the younger age range of vCJD cases.

PMID- 11343745
TI  - US expert group rejects link between MMR and autism.

PMID- 11343746
TI  - Sweet taste of success.

PMID- 11343747
TI  - Early events in high altitude pulmonary oedema delineated.

PMID- 11343748
TI  - Should endarterectomy decisions be based on non-invasive imaging?

PMID- 11343749
TI  - Cancer paper retracted.

PMID- 11343751
TI  - Looking at the molecular explanation for obesity.

PMID- 11343752
TI  - UK's controversial health and social care bill steams ahead.

PMID- 11343753
TI  - Yellow fever threat in India.

PMID- 11343754
TI  - Psychiatric reform law comes into effect in Brazil.

PMID- 11343755
TI  - Drug firms lose patent rights lawsuit against South Africa's government.

PMID- 11343756
TI  - Spain authorises clinical trial on heroin maintenance therapy.

PMID- 11343757
TI  - Ireland's doctors tackle institutional racism.

PMID- 11343758
TI  - Death rate of Aborigines in prison is increasing.

PMID- 11343760
TI  - Improving interpretation of clinical studies by use of confidence levels,
      clinical significance curves, and risk-benefit contours.
AB  - The process of interpreting the results of clinical studies and translating them
      into clinical practice is being debated. Here we examine the role of p values and
      confidence intervals in clinical decision-making, and draw attention to confusion
      in their interpretation. To improve result reporting, we propose the use of
      confidence levels and plotting of clinical significance curves and risk-benefit
      contours. These curves and contours provide degrees of probability of both the
      potential benefit of treatment and the detriment due to toxicity. Additionally,
      they provide clinicians with a mechanism of translating the results of studies
      into treatment for individual patients, thus improving the clinical decision
      making process. We illustrate the application of these curves and contours by
      reference to published studies. Confidence levels, clinical significance curves,
      and risk-benefit contours can be easily calculated with a hand calculator or
      standard statistical packages. We advocate their incorporation into the published
      results of clinical studies.

PMID- 11343761
TI  - Effect of sex hormones on cardiac mass.
AB  - Increased left-ventricular mass is an important cardiovascular risk factor for
      morbidity and mortality. Apart from obvious differences in cardiac size, the
      changes in left-ventricular mass in response to age and hypertrophic stimuli are
      very different in men and women. Whereas left-ventricular mass increases with age
      in apparently healthy women, it remains constant in men. Under increased cardiac
      loading conditions, such as hypertension or aortic stenosis, this disparity
      between sexes is even more striking. Findings are especially pronounced in people
      aged 50 years or older, in whom reproductive hormone concentrations have fallen.
      Whether the differences in left-ventricular mass changes are related to
      endogenous sex-hormone concentrations has never been shown. Androgens have
      anabolic effects on cardiac cells, and oestrogens have antiproliferative
      properties, we therefore postulate that the normal decline in endogenous sex
      hormones with age has contrary effects on ventricular mass in men and women in
      normal and pathological states.

PMID- 11343762
TI  - Should surgeons treat diabetes in severely obese people?

PMID- 11343770
TI  - Narcissus drowned.

PMID- 11343771
TI  - Aberrations of chromosome 8 in 16 breast cancer cell lines by comparative genomic
      hybridization, fluorescence in situ hybridization, and spectral karyotyping.
AB  - Comparative genomic hybridization (CGH) studies have shown that chromosome 8 is a
      frequent target for chromosomal aberrations in breast cancer. We characterized
      these aberrations of chromosome 8 in 16 breast cancer cell lines (BT-474, BT-549,
      CAMA-1, DU-4475, MCF-7, MDA-MB-134, MDA-MB-157, MDA-MB-361, MDA-MB-415, MDA-MB
      436, MPE600, SK-BR-3, T-47D, UACC-812, UACC-893 and ZR-75-1) by CGH, fluorescence
      in situ hybridization (FISH) with arm- and locus-specific probes, and spectral
      karyotyping (SKY). Chromosome 8 was structurally abnormal in 13 of 16 cell lines.
      Loss of 8p was detected in nine cell lines, gain of entire 8q in six cell lines,
      8q21-qter in three, 8q23-qter in two, and 8q12-qter and 8p21-q21 in one cell
      line. Extra copies of the C-MYC oncogene were found in 11 cell lines, but high
      level amplification only in SK-BR-3. Derivative chromosomes including material
      from chromosomes 8 were complex, and the breakpoints were strikingly dissimilar.
      Chromosome 11 was the most frequent translocation partner with chromosome 8 (in 7
      cell lines). Isochromosomes and/or isoderivative 8q were found in four cell
      lines. The high frequency and complexity of alterations at 8q indicate a
      significant pathogenetic role in breast cancer. The high-level amplification of c
      myc is less common than previously thought.

PMID- 11343773
TI  - Correlation between centrosome abnormalities and chromosomal instability in human
      pancreatic cancer cells.
AB  - Chromosomal instability, characterized by abnormal numbers or structures of
      chromosomes, is a common feature of human cancers, but the mechanisms behind
      these changes are still unclear. Since centrosomes play a pivotal role in
      balanced chromosomal segregation during mitosis, we attempted to investigate the
      association between centrosome abnormalities and chromosomal instability in a
      large number of human pancreatic cancer cell lines. Immunofluorescence microscopy
      revealed centrosomes that were highly atypical with respect to their size, shape,
      and number in most cell lines. These abnormal centrosomes contributed to the
      assembly of multipolar spindles, resulting in defective mitosis and chromosome
      mis-segregation. Interestingly, a high frequency of centrosome defects inversely
      correlated with the growth rate of cells in culture. Fluorescence in situ
      hybridization revealed a dramatic variation of chromosome numbers in cell lines
      with the defective centrosome phenotype. Furthermore, a significant positive
      correlation existed between the level of centrosome defects and the level of
      chromosomal imbalances. These results indicate that centrosome abnormalities can
      lead to spindle disorganization and chromosome segregation errors, which may
      drive the accumulation of chromosomal alterations. Thus, defects in centrosome
      function may be an underlying cause of genetic instability in human pancreatic
      cancers.

PMID- 11343772
TI  - Additional t(11;17)(q23;q21) in a patient with Philadelphia-positive mixed
      lineage antigen-expressing leukemia.
AB  - We describe very uncommon phenotypic and cytogenetic findings in a 40-year-old
      female with blast phase of Philadelphia chromosome (Ph)-positive CML. In addition
      to the t(9;22)(q34;q11) that was detected in all metaphases, a t(11;17)(q23;q21)
      was identified in 15 of 20 metaphases. Reverse transcription-polymerase chain
      reaction showed the major and minor bcr/abl fusion transcripts in the cells from
      a bone marrow (BM) sample. Fluorescence in situ hybridization (FISH) analysis
      also showed that fusion signals of the bcr and abl probes were found in 95% of
      blastic cells and in 64% of neutrophils. MLL gene rearrangement was also detected
      in some blastic cells but not in neutrophils by FISH analysis. Phenotypically,
      blastic cells expressed mixed lineage antigens such as CD34, CD33, CD13, CD19,
      CD7, and CD41. Immunogenotypically, some population of BM cells showed monoclonal
      rearrangements of immunoglobulin heavy chain and T-cell receptor gamma chain
      genes by Southern blot analysis. Clinical course was aggressive, and therapy was
      poorly tolerated. Such findings seem to support an association between Ph and an
      abnormality of 11q23 with poor prognosis, and suggest that the expression of both
      abnormal genes may be related to this mixed lineage antigen-expressing leukemia.

PMID- 11343774
TI  - Co-existence of alternative forms of 8q gain in cytogenetic clones of three
      patients with acute myeloid leukemia, pointing to 8q22 approximately 8qter as a
      region of biologic significance.
AB  - Clonal trisomy 8 chromosome abnormalities can be detected in 15% of patients with
      acute myeloid leukemia (AML). The most common form of change is complete gain of
      the whole chromosome 8, followed by partial gains in unbalanced forms. The
      biologic consequences of trisomy 8 remain unclear, but a gene dosage effect is
      suspected. We report on three patients with AML who had alternative forms of
      chromosome 8 gain in their bone marrow cells. The partial gains resulted from a
      breakpoint in the chromosome band 8q22. This indicates that the region 8q22 to
      8qter may be of particular pathogenetic importance.

PMID- 11343775
TI  - The application of comparative genomic hybridization as an additional tool in the
      chromosome analysis of acute myeloid leukemia and myelodysplastic syndromes.
AB  - In acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) there are
      frequently complex karyotypes with multiple structurally altered chromosomes,
      many of which are marker chromosomes of unknown origin. The aim of this study was
      to apply comparative genomic hybridization (CGH) to cases of AML or MDS in
      transformation submitted for routine cytogenetic analysis to investigate whether
      this approach would yield any further information and, if possible, to predict
      which cases would benefit from CGH analysis. Nineteen cases with AML or MDS in
      transformation were analyzed. CGH revealed nine cases with gains or losses of
      chromosomal material. In six of these cases the chromosomal location of this
      material was not apparent from cytogenetic analysis especially when multiple
      markers were present. By using fluorescence in situ hybridization (FISH) with
      specific libraries for the chromosome regions that showed discordance between CGH
      and conventional cytogenetics, we were able to identify the chromosome location
      of material within the karyotype. In this group of six patients, four cases of an
      unbalanced translocation involving regions of chromosomes 5 and 17 were
      characterized. Three of these cases had additional abnormalities, including two
      cases with regions of amplification in which oncogenes are located (MYC, MLL) and
      one case with a dic(7;21)(p10;p10). In all six cases it was possible to
      characterize complex chromosomal aberrations such as derivative chromosomes,
      marker chromosomes, and ring chromosomes. This study demonstrates that CGH can
      detect true gain and loss of critical chromosome regions more accurately than
      conventional karyotyping in cases with very complex karyotypes, and can thus
      prove useful in predicting prognosis and pinpointing areas of the genome that
      require further study. Also, CGH can be a useful technique to identify the origin
      of marker chromosomes, and it can assist in choice of probes for confirmatory
      FISH, when there is no clue provided from the analysis of G-banded chromosomes.

PMID- 11343776
TI  - DNA amplification and chromosomal translocations are accompanied by chromosomal
      instability: analysis of seven human colon cancer cell lines by comparative
      genomic hybridization and spectral karyotyping.
AB  - Genetic instability in human cancers is classified as chromosomal instability
      (CIN) or microsatellite instability (MIN). DNA amplification and translocations
      are observed frequently in various cancers. We used comparative genomic
      hybridization (CGH) and spectral karyotyping (SKY) to study seven human colon
      cancer cell lines and investigate the relations among genetic instability, DNA
      amplification, and chromosomal translocations. DNA amplification was found in
      five cell lines (COLO320DM, COLO201, WiDr, CoCM-1, and CACO-2), and all were
      aneuploid. In these five cell lines, segments of chromosomes were translocated to
      other chromosomes. In contrast, cell lines with MIN, DLD-1, and LoVo did not show
      DNA amplification. The LoVo cells with MIN were considered near diploid and
      contained translocations. These findings suggest that DNA amplification and
      chromosomal translocations are accompanied by CIN.

PMID- 11343777
TI  - Mapping the chromosome 16 cadherin gene cluster to a minimal deleted region in
      ductal breast cancer.
AB  - The cadherin family of cell adhesion molecules has been implicated in tumor
      metastasis and progression. Eight family members have been mapped to the long arm
      of chromosome 16. Using radiation hybrid mapping, we have located six of these
      genes within a cluster at 16q21-q22.1. In invasive lobular carcinoma of the
      breast frequent LOH and accompanying mutation affect the CDH1 gene, which is a
      member of this chromosome 16 gene cluster. CDH1 LOH also occurs in invasive
      ductal carcinoma, but in the absence of gene mutation. The proximity of other
      cadherin genes to 16q22.1 suggests that they may be affected by LOH in invasive
      ductal carcinomas. Using the mapping data, microsatellite markers were selected
      which span regions of chromosome 16 containing the cadherin genes. In breast
      cancer tissues, a high rate of allelic loss was found over the gene cluster
      region, with CDH1 being the most frequently lost marker. In invasive ductal
      carcinoma a minimal deleted region was identified within part of the chromosome
      16 cadherin gene cluster. This provides strong evidence for the existence of a
      second 16q22 suppressor gene locus within the cadherin cluster.

PMID- 11343778
TI  - Chromosomal analyses of 52 cases of follicular lymphoma with t(14;18), including
      blastic/blastoid variant.
AB  - We have identified 52 patients of follicular lymphoma (FL) with
      t(14;18)(q32;q21). Histologically, the lymphomas were placed into six groups
      according to their cellular composition and growth pattern. Chromosome analysis
      revealed that all cases but one had additional secondary chromosomal
      abnormalities. The most frequent numerical aberrations were gains of chromosomes
      7 (38%), X (36%), 5 (15%), 12 (15%), 18/der(18)t(14;18) (25%), and 21 (15%).
      Structural abnormalities of chromosome 1 were seen in 19 tumors (36%) affecting
      both arms with breakpoints clustered at 1p36. Other structural abnormalities
      included partial deletions of 6q, 10q, and 13q. Breakpoint at 8q24 was seen in
      four cases. The chromosome aberrations were correlated with the morphological
      subtypes of follicular lymphoma. Gain of chromosome 7 appeared to be associated
      with follicular large cell lymphoma. The incidence of trisomy 5 and 12, and 13q-
      was higher in follicular lymphoma with aggressive histological features than in
      low-grade lymphoma. In addition, complexity of the karyotype and high degree of
      polyploidy increased with the grade. The most valuable cytogenetic markers in the
      t(14;18) lymphomas are those involving 8q24 which was found exclusively in the
      blastic/blastoid variant FL. Therefore, chromosome analysis in relation to
      histologic pattern of follicular lymphoma can provide additional information in
      predicting tumor evolution and transformation to a higher-grade malignancy.

PMID- 11343779
TI  - Fanconi anemia. a statistical evaluation of cytogenetic results obtained from
      South African families.
AB  - Fanconi anemia (FA) is a rare autosomal recessive genetic disorder showing
      progressive bone marrow failure, and various phenotypic abnormalities. The
      lymphocytes show an increased sensitivity to the clastogenic agents diepoxybutane
      (DEB) or mytomycin C (MMC), measured as chromosomal aberrations. Statistical
      analysis of chromosome aberration yield showed that: (i) differentiation between
      obligate carriers and the control group was not possible; (ii) homozygotes were
      clearly distinguishable from heterozygotes as well as from controls by analyzing
      only 20 metaphase spreads per person; (iii) most of the FA patients had only one
      cell line present as measured by distribution of chromosomal damage among cells
      analyzed; (iv) and when the DEB sensitivity of a patient was high, the amount of
      cells without damage was low.

PMID- 11343780
TI  - No increased frequency of trisomies 8 and 9 by fluorescence in situ hybridization
      in untreated patients with essential thrombocythemia.
AB  - Essential thrombocythemia (ET) is one of the diseases included among the
      myeloproliferative disorders in which trisomies for chromosomes 8 and 9 commonly
      occur. In ET, only a few patients are known to show clonal abnormalities. With
      fluorescence in situ hybridization (FISH), interphase cells can be evaluated and
      clones can be detected even though not revealed by conventional cytogenetic
      methods. By using FISH for enumeration of chromosomes 8 and 9 in bone marrow
      cells, we studied 22 patients with ET; 20 of them were investigated at the time
      of diagnosis when they were still untreated with myelosuppressive agents. Only
      two patients had trisomy 8; one of them was also found to have +8 with
      conventional cytogenetics. None of the patients had trisomy 9; two patients had
      borderline values in comparison to a control group. Thus, in ET, no increased
      frequency of patients with trisomy for 8 or 9 at the time of diagnosis could be
      detected with FISH.

PMID- 11343781
TI  - No evidence for deletions of the NBS1 gene in lymphomas.
AB  - Patients with Nijmegen breakage syndrome (NBS) have a high risk to develop
      malignant diseases, most frequently B-cell lymphomas. The NBS gene product,
      nibrin, is involved in DNA recombination repair, a function shared with known
      tumor suppressor genes like BRCA1 and BRCA2. This led us to investigate whether
      NBS acts as tumor suppressor gene in the development of non-Hodgkin lymphomas.
      Therefore, we performed fluorescence in situ hybridization analysis using a BAC
      clone containing the entire NBS1 region on eight B-cell and eight T-cell
      lymphomas, including one B-cell and two T-cell lymphomas with structural
      abnormalities of 8q. None of the tumors showed a deletion of the NBS1 gene,
      demonstrating that deletion of the NBS1 gene is not a major cause or a primary
      event in tumorigenesis of human B- and T-cell lymphomas.

PMID- 11343782
TI  - Comparative genomic hybridization analysis of nasopharygeal carcinoma: consistent
      patterns of genetic aberrations and clinicopathological correlations.
AB  - To define the patterns of genetic imbalances in nasopharyngeal carcinoma (NPC),
      we studied 30 primary NPC tumors with comparative genomic hybridization (CGH).
      The common sites of chromosomal gains were found in descending order of frequency
      in 12p11.2-p12 (36%), 12q14-q21 (33%), 2q24-q31 (23%), 1q31-qter (20%), 3q13
      (20%), 1q13.3 (20%), 5q21 (17%), 6q14-q22 (13%), 7q21 (13%), 8q11.2-q23 (13%) and
      18q12-qter (13%). The common sites of chromosomal loss were at 3p14-p21 (20%),
      11q23-qter (20%), 16q21-qter (17%) and 14q24-qter (13%). Correlation with
      clinicopathologic features showed that 3p loss was associated with a
      significantly higher risk of death related to recurrence as compared with
      patients without 3p loss (50% vs. 9%, P=.029). The presence of 16q loss was
      associated with more advanced stage tumors (stages I & II: 6% vs. stages III &
      IV: 33%, P=.046). We conclude that consistent patterns of genetic imbalances can
      be observed in NPC. Deletion of 3p and 16q were associated with higher risk of
      tumor recurrence and advanced stage cancer.

PMID- 11343783
TI  - Cytogenetic instability, predominantly involving chromosome 1, is characteristic
      of elastofibroma.
AB  - Elastofibroma, an unusual pseudotumor composed of excessive collagen and abnormal
      elastic fibers, has rarely been subjected to cytogenetic analysis. Only two cases
      have been previously defined, both of which demonstrated nonclonal abnormalities.
      In the present study, three cases of elastofibroma were cytogenetically analyzed.
      Abnormalities of the short arm of chromosome 1 were seen in all three cases
      (either clonally or as the most frequently involved region among nonclonal
      aberrations). In addition, a translocation involving chromosomes 8 and 12 was
      detected as a clonal rearrangement in one of the three cases. The observation of
      clonal abnormalities in elastofibroma suggests that this lesion may represent a
      neoplastic rather than a reactive process.

PMID- 11343784
TI  - Low incidence of TEL/AML1 fusion and TEL deletion in Korean childhood acute
      leukemia by extra-signal fluorescence in situ hybridization.
AB  - TEL/AML1 fusion in acute leukemia results from cryptic translocation of
      chromosome 12 and 21, the presence of which suggests a favorable prognosis. The
      incidence of TEL/AML1 fusion in B-lineage ALL is approximately 25%, but the
      incidence in Korea has not yet been reported. To investigate the incidence of
      TEL/AML1 fusion and TEL deletion, bone marrow specimens from 77 Korean children
      with newly diagnosed acute leukemia were analyzed by FISH. We applied extra
      signal FISH to discriminate a true TEL/AML1 fusion from a false-positive fusion
      signal. To determine the cut-off value of the TEL/AML1 fusion signal, 20 normal
      bone marrow specimens and 28 normal peripheral blood specimens were also
      analyzed. The frequency of patients with TEL/AML1 fusion was 13.3% (4 cases)
      among 30 B-lineage ALL and 9.5% among 42 ALL. One TEL/AML1 fusion-positive
      patient was also found among 4 acute biphenotypic leukemias. TEL/AML1 fusion was
      not found in any samples from patients with T-lineage ALL or AML. The incidence
      of TEL deletion was 6.7% (2 cases) among 30 B-lineage ALL and 4.8% among 42 ALL.
      The incidences of TEL/AML1 fusion and TEL deletion in Korean children with acute
      leukemia appear to be lower than those in other countries, suggesting a racial
      difference.

PMID- 11343785
TI  - Trisomy 21 and isodicentric chromosome 21 in Kostmann syndrome following
      treatment with G-CSF.
AB  - A child with Kostmann syndrome, or severe congenital neutropenia, developed
      myelodysplastic syndrome after 6 years of treatment with rhG-CSF. The bone marrow
      karyotype showed acquired trisomy 21, and in some cells pentasomy 21 due to two
      isodicentric chromosomes 21. This is the second report of a patient with Kostmann
      syndrome and acquired trisomy 21.

PMID- 11343786
TI  - Allosteric regulation of the cAMP receptor protein.
AB  - The cyclic AMP receptor protein (CRP) of Escherichia coli is a dimer made up of
      identical subunits. Each CRP subunit contains a cyclic nucleotide binding pocket
      and the CRP dimer exhibits negative cooperativity in binding cAMP. In solutions
      containing cAMP, CRP undergoes sequential conformation changes from the inactive
      apo-form through the active CRP:(cAMP)(1) complex to the less active
      CRP:(cAMP)(2) complex depending on the cAMP concentration. Apo-CRP binds DNA with
      low affinity and no apparent sequence specificity. The CRP:(cAMP)(1) complex
      exhibits high affinity, sequence-specific DNA binding and interacts with RNA
      polymerase, whether free in solution or complexed with DNA. The results of
      genetic, biochemical and biophysical studies have helped to uncover many of the
      details of cAMP-mediated allosteric control over CRP conformation and activity as
      a transcription factor. These studies indicate that cAMP binding produces only
      small, but significant, changes in CRP structure; changes that include subunit
      realignment and concerted motion of the secondary structure elements within the C
      terminal DNA binding domain of each subunit. These adjustments promote CRP
      surface-patch interaction with RNA polymerase and protrusion of the F-helix to
      promote CRP site-specific interaction with DNA. Interactions between CRP and RNA
      polymerase at CRP-dependent promoters produce active ternary transcription
      complexes.

PMID- 11343787
TI  - Crystal structure of destripeptide (B28-B30) insulin: implications for insulin
      dissociation.
AB  - Destripeptide (B28-B30) insulin (DTRI) is an insulin analogue that has much
      weaker association ability than native insulin but keeps most of its biological
      activity. It can be crystallized from a solution containing zinc ions at near
      neutral pH. Its crystal structure has been determined by molecular replacement
      and refined at 1.9 A resolution. DTRI in the crystal exists as a loose hexamer
      compared with 2Zn insulin. The hexamer only contains one zinc ion that
      coordinates to the B10 His residues of three monomers. Although residues B28-B30
      are located in the monomer-monomer interface within a dimer, the removal of them
      can simultaneously weaken both the interactions between monomers within the dimer
      and the interactions between dimers. Because the B-chain C-terminus of insulin is
      very flexible, we take the DTRI hexamer as a transition state in the native
      insulin dissociation process and suggest a possible dissociation process of the
      insulin hexamer based on the DTRI structure.

PMID- 11343788
TI  - Structure and function analysis of urinary trypsin inhibitor (UTI):
      identification of binding domains and signaling property of UTI by analysis of
      truncated proteins.
AB  - The binding of urinary trypsin inhibitor (UTI) to its binding sites/receptors on
      tumor cells inhibits cell invasion in a number of experimental systems and that
      UTI downregulates constitutive and phorbol ester-induced urokinase production by
      certain tumor cells. To determine whether the carbohydrate moieties and core
      protein are required for urokinase suppression, we obtained UTI derivatives that
      contained O-glycoside-linked N-terminal glycopeptide (UTIm1), N-glycoside-linked
      C-terminal tandem Kunitz domains (UTIm2), UTI lacking O-glycoside (UTIc), asialo
      UTI (UTIa), UTI lacking N-glycoside (UTIn), purified Kunitz domain II of UTI (HI
      8), and recombinant Kunitz domain II of UTI (R-020). The IC(50) of inhibiting
      binding of (125)I-labeled UTI to cells was indistinguishable for UTIa, UTIn and
      intact UTI, whereas the IC(50) for inhibiting binding of (125)I-labeled UTI to
      cells was 2.5-, 25- and 29-fold greater for UTIm1, UTIm2 and UTIc than for native
      UTI. We next looked at the suppression of the urokinase expression by UTI
      derivatives. An enzyme-linked immunosorbent assay was carried out to measure
      secreted and cell-associated urokinase. Intact UTI, UTIa, or UTIn effectively
      suppressed urokinase expression, but UTIm1, UTIm2, UTIc, HI-8 and R-020 had no
      significant effect. These data show that UTI requires either the N-terminal
      extension with the O-linked carbohydrate moiety (chondroitin 4-sulfate sugar side
      chain; Ala1 to Lys21 residues) or the Kunitz domain I (Lys22 to Arg77 residues)
      of UTI to bind to cells, but the urokinase expression was inhibited only by the O
      glycoside-linked core protein without the N-glycoside side chain.

PMID- 11343789
TI  - Mutagenesis of amino acid residues in the SHV-1 beta-lactamase: the premier role
      of Gly238Ser in penicillin and cephalosporin resistance.
AB  - The recent availability of the SHV-1 beta-lactamase crystal structure provides a
      framework for the understanding of the functional role of amino acid residues in
      this enzyme. To that end, we have constructed by site-directed mutagenesis 18
      variants of the SHV beta-lactamase: an extended spectrum group: Gly238Ser,
      Gly238Ser-Glu240Lys, Asp104Lys-Gly238Ser, Asp104Lys-Thr235Ser-Gly238Ser,
      Asp179Asn, Arg164His, and Arg164Ser; an inhibitor resistant group: Arg244Ser,
      Met69Ile, Met69Leu, and Ser130Gly; mutants that are synergistic with those that
      confer resistance to oxyimino-cephalosporins: Asp104Glu, Asp104Lys, Glu240Lys,
      and Glu240Gln; and structurally conserved mutants: Thr235Ser, Thr235Ala and
      Glu166Ala. Among the extended spectrum group the combination of high-level
      ampicillin and cephalosporin resistance was demonstrated in the Escherichia coli
      DH10B strains possessing the Gly238Ser mutation: Gly238Ser, Gly238Ser-Glu240Lys,
      Asp104Lys-Gly238Ser, and Asp104Lys-Thr235Ser-Gly238Ser. Of the inhibitor
      resistant group, the Ser130Gly mutant was the most resistant to
      ampicillin/clavulanate. Using a polyclonal anti-SHV antibody, we assayed steady
      state protein expression levels of the SHV beta-lactamase variants. Mutants with
      the Gly238Ser substitution were among the most highly expressed. The Gly238Ser
      substitution resulted in an improved relative k(cat)/K(m) value for cephaloridine
      and oxyimino-cephalosporins compared to SHV-1 and Met69Ile. In our comparative
      survey, the Gly238Ser and extended spectrum beta-lactamase variants containing
      this substitution exhibited the greatest substrate versatility against
      penicillins and cephalosporins and greatest protein expression. This defines a
      unique role of Gly238Ser in broad-spectrum beta-lactam resistance in this family
      of class A beta-lactamases.

PMID- 11343790
TI  - Amino acid structure and characterization of a heterodimeric disintegrin from
      Vipera lebetina venom.
AB  - A heterodimeric disintegrin designed as lebein was isolated from crude Vipera
      lebetina venom using gel filtration, anion and cation exchange chromatographies
      on FPLC. The amino acid sequence of each subunit determined by Edman degradation
      contains 64 residues with ten half-cystines and an RGD site at the C-terminal
      part of the molecule. The molecular mass of native lebein determined by mass
      spectrometry was found to be 14083.4 Da and those of alpha and beta subunits were
      6992.05 and 7117.62, respectively. These value are in good agreement with those
      calculated from the sequences. This protein strongly inhibits ADP induced
      platelet aggregation on human platelet rich plasma with IC(50)=160 nM. Sequences
      of this protein subunits displayed significant sequence similarities with many
      other monomeric and dimeric disintegrins reported from snake venoms. We
      identified an amino acid residue (N) in the hairpin loop of both subunits
      (CNRARGDDMNDYC) which is different from all other reported motifs of disintegrins
      and this subtle difference may contribute to the distinct affinities and
      selectivities of this class of proteins.

PMID- 11343791
TI  - A 28 kDa protein of the Bacillus thuringiensis serovar shandongiensis isolate 89
      T-34-22 induces a human leukemic cell-specific cytotoxicity.
AB  - A 28 kDa protein that exhibits cytocidal activity specific for human leukemic T
      (MOLT-4) cells was purified from proteinase K-digested parasporal inclusion of a
      Bacillus thuringiensis serovar shandongiensis isolate. The N-terminal sequence of
      the protein was identical with that of the 32 kDa protein, regarded as a
      protoxin, of the inclusion proteins. The median effective concentration of this
      protein was 0.23 microg/ml against MOLT-4 cells and its specific activity was 7.9
      times greater than that of the whole inclusion proteins. The 28 kDa protein
      induced necrosis-like cytotoxicity against MOLT-4 cells and the cytopathic effect
      with the passage of time was characterized by cell swelling, nuclear membrane
      isolation and chromatin condensation.

PMID- 11343792
TI  - A processing enzyme cleaving avian progastrin at post-Phe bonds.
AB  - Neuroendocrine peptides mature partly through endoproteolytic processing of long
      precursor forms. Best characterised is cleavage at mono- and dibasic residues,
      but additional sites also exist. Among these is post-Phe cleavage, first
      suggested to participate in the processing of chicken progastrin. In order to
      characterise this new mechanism, antibodies recognising the processing products
      of post-Phe cleavage of chicken progastrin were produced for radioimmunoassay
      measurements and immunocytochemistry. High concentrations of the carboxyamidated
      C-terminus and the N-terminus of gastrin-53 were measured in extracts of the
      antrum. In addition, significant amounts were detected using an assay specific
      for the N-terminus of gastrin-30 and with another assay for the C-terminus of the
      corresponding peptide, gastrin-53(1-23), obtained after cleavage at the Phe(23)
      Ala(24) bond of gastrin-53. Colocalisation in antral G-cells of the N-termini of
      gastrin-53 and gastrin-30 and of the C-terminus of gastrin-53(1-23) was confirmed
      by immunohistochemistry. Finally, we identified the intact N-terminal 1-23
      fragment of gastrin-53 complementary to gastrin-30, verifying endoproteolytic
      cleavage at the Phe(23)-Ala(24) bond. Taken together, the results support the
      existence of vertebrate endoprotease cleaving hormone precursors at post-Phe
      sites.

PMID- 11343793
TI  - The importance of histidine residues in human ecto-nucleoside triphosphate
      diphosphohydrolase-3 as determined by site-directed mutagenesis.
AB  - Most ecto-nucleoside triphosphate diphosphohydrolases (eNTPDases) are inhibited
      by the histidine reagent diethyl pyrocarbonate (DEPC), while being resistant to
      inhibition by many other chemical modification agents. We used site-directed
      mutagenesis to investigate the sites of modification responsible for DEPC
      inhibition. First, we constructed the mutations H135A and R67H in eNTPDase-3 to
      address the possibility that, in eNTPDase-3, histidine 135 compensates for the
      lack of a histidine in apyrase conserved region (ACR) 1, present in all other
      membranous eNTPDases (but replaced by R67 in ACR1 of eNTPDase-3). We found
      histidine 135 is a major, but not the sole, target for DEPC-induced inhibition in
      eNTPDase-3. In addition, analysis of the R67H mutant led us to conclude that this
      site is important for DEPC inactivation of other eNTPDases. We also mutated
      singly and collectively three of the most conserved histidine residues present in
      eNTPDase-3 (129, 257 and 447) to alanine. None of the single, conserved histidine
      mutations nor the triple histidine mutation inactivated the enzyme or decreased
      susceptibility to DEPC inhibition. However, changes in the tendency of monomers
      to self-associate were noted, and the triple histidine mutant exhibited a higher
      nucleotidase specific activity than the wild-type.

PMID- 11343794
TI  - Synthesis and hydrolysis by cathepsin B of fluorogenic substrates with the
      general structure benzoyl-X-ARG-MCA containing non-natural basic amino acids at
      position X.
AB  - We synthesized one series of fluorogenic substrates for cathepsin B derived from
      the peptide Bz-F-R-MCA (Bz=benzoyl, MCA=7-methyl-coumarin amide) substituting Phe
      at the P(2) position by non-natural basic amino acids that combine a positively
      charged group with aromatic or aliphatic radicals at the same side chain, namely,
      4-aminomethyl-phenylalanine, 4-guanidine-phenylalanine, 4-aminomethyl-N-isopropyl
      phenylalanine, 3-pyridyl-alanine, 4-piperidinyl-alanine, 4-aminomethyl-cyclohexyl
      alanine, 4-aminocyclohexyl-alanine, and N(im)-dimethyl-histidine. Bz-F-R-MCA was
      the best substrate for cathepsin B but also hydrolyzed Bz-R-R-MCA with lower
      efficiency, since the protease accepts Arg at S(2) due to the presence of
      Glu(245) at the bottom of this subsite. The presence of the basic non-natural
      amino acids at the P(2) position of the substrate partially restored the
      catalytic efficiency of cathepsin B. All the kinetic parameters for hydrolysis of
      the peptides described in this paper are in accordance with the structures of the
      S(2) pocket previously described. In addition, the substrate with 4
      aminocyclohexyl-alanine presented the highest affinity to cathepsin B although
      the peptide was obtained from a mixture of cis/trans isomers of the amino acid
      and we were not able to separate them. For comparison all the obtained substrates
      were assayed with cathepsin L and papain.

PMID- 11343795
TI  - Ruminant brain ribonucleases: expression and evolution.
AB  - Molecular evolutionary analyses of mammalian ribonucleases have shown that gene
      duplication events giving rise to three paralogous genes occurred in ruminant
      ancestors. One of these genes encodes a ribonuclease identified in bovine brain.
      A peculiar feature of this enzyme and orthologous sequences in other ruminants
      are C-terminal extensions consisting of 17-27 amino acid residues. Evidence was
      obtained by Western blot analysis for the presence of brain-type ribonucleases in
      brain tissue not only of ox, but also of sheep, roe deer and chevrotain (Tragulus
      javanicus), a member of the earliest diverged taxon of the ruminants. The C
      terminal extension of brain-type ribonuclease from giraffe deviates much in
      sequence from orthologues in other ruminants, due to a change of reading frame.
      However, the gene encodes a functional enzyme, which could be expressed in
      heterologous systems. The messenger RNA of bovine brain ribonuclease is not only
      expressed at a high level in brain tissue but also in lactating mammary gland.
      The enzyme was isolated and identified from this latter tissue, but was not
      present in bovine milk, although pancreatic ribonucleases A and B could be
      isolated from both sources. This suggests different ways of secretion of the two
      enzyme types, possibly related to structural differences. The sequence of the
      brain-type RNase from chevrotain suggests that the C-terminal extensions of
      ruminant brain-type ribonucleases originate from deletions in the ancestral DNA
      (including a region with stop codons), followed by insertion of a 5-8-fold
      repeated hexanucleotide sequence, coding for a proline-rich polypeptide.

PMID- 11343796
TI  - Molecular cloning and functional characterization of a unique multipotent
      polyphenol oxidase from Marinomonas mediterranea.
AB  - Marinomonas mediterranea is a recently isolated melanogenic marine bacterium
      containing laccase and tyrosinase activities. These activities are due to the
      expression of two polyphenol oxidases (PPOs), a blue multicopper laccase and an
      SDS-activated tyrosinase. The gene encoding the first one, herein denominated M.
      mediterranea PpoA, has been isolated by transposon mutagenesis, cloned and
      expressed in Escherichia coli. Its predicted amino acid sequence shows the
      existence of a signal peptide and four copper-binding sites characteristic of the
      blue multicopper proteins, including all fungal laccases. In addition, two
      additional putative copper-binding sites near its N-terminus are also present.
      Recombinant expression in E. coli of this protein clearly demonstrates its
      multipotent capability, showing both laccase-like and tyrosinase-like activities.
      This is the first prokaryotic laccase sequenced and the first PPO showing such
      multipotent catalytic activity. The expression of several truncated products
      indicates that the four copper-binding sites typical of blue multicopper proteins
      are essential for the laccase activity of this enzyme. However, the last two of
      these sites are not necessary for tyrosine hydroxylase activity as this activity
      is retained in a truncated product containing the first two sites as well as the
      extra histidine-rich clusters close to the N-terminus of the protein.

PMID- 11343797
TI  - Effect of N-domain on the stability of elongation factor Ts from Thermus
      thermophilus.
AB  - Elongation factor Ts (EF-Ts) from Thermus thermophilus forms a stable,
      functionally active homodimer in solution. Its monomer is composed of two
      domains: amino-terminal domain containing 50 amino acid residues and a larger,
      146 residues long, C-domain which participates in dimerization of EF-Ts. Effect
      of removal of the N-domain on the conformational stability of EF-Ts has been
      studied. For comparison, the stabilities of both the full-length EF-Ts and its C
      domain were studied by differential scanning calorimetry, electronic absorption
      and fluorescence spectroscopies over a pH range from 4 to approximately 13.
      Thermal denaturation of EF-Ts and of C-domain, followed by circular dichroism at
      222 nm, at pH 7.0, and the pH dependence of the fluorescence of the single
      tryptophan 30 residue indicate a conformational instability of the N-domain.
      While N-domain does not affect the stability of full-length EF-Ts at acidic pH,
      its removal leads to stabilization of the rest of the protein at basic pH. This
      is reflected by higher values of transition temperatures and calorimetric
      enthalpies of C-domain as compared to the full-length EF-Ts. High mobility of the
      N-domain in alkaline pH conditions decreased the thermal stability of covalently
      linked C-domain of EF-Ts. An increase in intramolecular interactions at acidic pH
      together with a decrease of conformational entropies of the thermally denatured
      proteins most likely diminishes this destabilization effect.

PMID- 11343798
TI  - Mutational analyses of cysteine residues of bovine dihydrodiol dehydrogenase 3.
AB  - The cloning, bacterial expression and purification of bovine liver cytosolic
      dihydrodiol dehydrogenase 3 (DD3) cDNA (1330 bp in full length) using the pKK223
      3 expression vector has been reported previously. Recombinant DD3 (rDD3) was
      characterized in terms of its substrate specificity and inhibitor sensitivity
      [Terada et al., Adv. Exp. Biol. Res. 414 (1997) 543-553]. The nucleotide sequence
      of DD3 cDNA completely matched with that of bovine liver-type prostaglandin F
      synthase [Suzuki et al., J. Biol. Chem. 274 (1999) 241-248]. In the present
      study, we succeeded in high level expression of rDD3 in Escherichia coli BL21
      (DE3) using the pET28a expression vector. rDD3 was easily and quickly purified to
      apparent homogeneity by one-step column chromatography using Ni(2+)-affinity
      resin. Furthermore, rDD3 showed essentially the same substrate specificity and
      inhibitor sensitivity to that of purified liver DD3. To analyze the role of
      cysteines (145, 154, 188, 193 and 206) in the enzymatic activity of DD3, site
      directed mutagenesis of DD3 using the polymerase chain reaction method was
      performed. Mutants (C145S, C154S, C188S, C193S and C206S) were analyzed for
      substrate specificity, cofactor binding and inactivation by disulfide (dithio
      bis(2-nitrobenzoic acid), alkylating reagent (N-ethylmaleimide) and oxidants
      (naphthoquinone and H(2)O(2)) Results indicated that these five cysteines of rDD3
      may not be directly involved in substrate or cofactor binding. Mutant C193S
      showed strong resistance to SH-reagents unlike wild-type DD3 (WT) or other
      mutants. Both the WT and the other mutants showed essentially the same
      sensitivity to SH-reagents. Cofactor (NADP(+)) protected mutants C145S, C188S and
      C206S from inactivation as well as WT, while NAD(+) was not protective. Our
      present results indicate that Cys193, which is located close to the NADP(+)
      binding site, may be involved in the alteration of enzymatic activity.

PMID- 11343799
TI  - Strong nucleic acid binding to the Escherichia coli RNase HI mutant with two
      arginine residues at the active site.
AB  - The biochemical properties of the mutant protein D10R/E48R of Escherichia coli
      RNase HI, in which Asp(10) and Glu(48) are both replaced by Arg, were
      characterized. This mutant protein has been reported to have metal-independent
      RNase H activity at acidic pH [Casareno et al. (1995) J. Am. Chem. Soc. 117,
      11011-11012]. The far- and near-UV CD spectra of this mutant protein were similar
      to those of the wild-type protein, suggesting that the protein conformation is
      not markedly changed by these mutations. Nevertheless, we found that this mutant
      protein did not show any RNase H activity in vitro. Instead, it showed high
      nucleic-acid-binding affinity. Protein footprinting analyses suggest that DNA/RNA
      hybrid binds to or around the presumed substrate-binding site of the protein. In
      addition, this mutant protein did not complement the temperature-sensitive growth
      phenotype of the rnhA mutant strain, E. coli MIC3001, even at pH 6.0, suggesting
      that it does not show RNase H activity in vivo as well. These results are
      consistent with a current model for the catalytic mechanism of the enzyme, in
      which Glu(48) is not responsible for Mg(2+) binding but is involved in the
      catalytic function.

PMID- 11343800
TI  - Identification of a bioactive domain in the amino-terminus of glucose-dependent
      insulinotropic polypeptide (GIP).
AB  - The incretins are a class of hormones released from the small bowel that act on
      the endocrine pancreas to potentiate insulin secretion in a glucose-dependent
      manner. Due to the requirement for an elevated glucose concentration for
      activity, the incretins, glucose-dependent insulinotropic polypeptide (GIP) and
      glucagon-like peptide-1, have potential in the treatment of non-insulin-dependent
      diabetes mellitus. A series of synthetic peptide GIP fragments was generated for
      the purpose of elucidating the bioactive domain of the molecule. Peptides were
      screened for stimulation of cyclic AMP (cAMP) accumulation in Chinese hamster
      ovary cells transfected with the rat islet GIP receptor. Of the GIP fragments
      tested, GIP(1-14) and GIP(19-30) demonstrated the greatest cAMP-stimulating
      ability over the range of concentrations tested (up to 20 microM). In contrast,
      GIP fragments corresponding to amino acids 15-42, 15-30, 16-30 and 17-30 all
      demonstrated weak antagonism of GIP(1-42) activity. Competitive-binding
      displacement studies indicated that these peptides were low-affinity ligands for
      the GIP receptor. To examine biological activity in vivo, a bioassay was
      developed in the anesthetized rat. Intravenous infusion of GIP(1-42) (1
      pmol/min/100 g) with a concurrent intraperitoneal glucose load (1 g/kg)
      significantly reduced circulating blood glucose excursions through stimulation of
      insulin release. Higher doses of GIP(1-14) and GIP(19-30) (100 pmol/min/100 g)
      also reduced blood glucose excursions.

PMID- 11343801
TI  - Binding features of chloroplast fructose-1,6-bisphosphatase-thioredoxin
      interaction.
AB  - It has been proposed that a hydrophobic groove surrounded by positively charged
      amino acids on thioredoxin (Trx) serves as the recognition and docking site for
      the interaction of Trx with target proteins. This model for Trx-protein
      interactions fits well with the Trx-mediated fructose-1,6-bisphosphatase (FBPase)
      activation, where a protruding negatively charged loop of FBPase would bind to
      this Trx groove, in a process involving both electrostatic and hydrophobic
      interactions. This model facilitates the prediction of Trx amino acid residues
      likely to be involved in enzyme binding. Site-directed mutagenesis of some of
      these amino acids, in conjunction with measurements of the FBPase activation
      capacity of the wild type and mutated Trxs, was used to check the model and
      provided evidence that lysine-70 and arginine-74 of pea Trx m play an essential
      role in FBPase binding. The binding parameters for the interaction between
      chloroplast FBPase and the wild type pea Trxs f and m, as well as mutated pea Trx
      m, determined by equilibrium dialysis in accordance with the Koshland-Nemethy
      Filmer model of saturation kinetics, provided additional support for the role of
      these basic Trx residues in the interaction with FBPase. These data, in
      conjunction with the midpoint redox potential (E(m)) determinations of Trxs,
      support the hydrophobic groove model for the interaction between chloroplast
      FBPase and Trx. This model predicts that differences in the FBPase activation
      capacity of Trxs arise from their different binding abilities.

PMID- 11343802
TI  - In vitro activity of MEKK2 and MEKK3 in detergents is a function of a valine to
      serine difference in the catalytic domain.
AB  - MEKK2 and MEKK3 are mitogen-activated protein kinase kinase kinases (MAP3
      kinases) of 70 and 71 kDa respectively that are markedly homologous (94%) in
      their kinase domains. Both MEKK2 and MEKK3 are able to activate the Jun kinase
      pathway in vivo. However, following routine immunoprecipitation in Triton X-100,
      MEKK2 but not MEKK3 is able to effectively phosphorylate both SEK-1 and MEK-1 and
      to undergo autophosphorylation. Unexpectedly, both MEKK2 and MEKK3 are functional
      in an in vitro kinase assay when cells are solubilized with the closely related
      detergent, NP-40. Given the high homology between these kinases, we set out to
      relate this differential sensitivity to Triton X-100 to differences in primary
      structure. A set of chimeric molecules were generated and the loss of activity in
      Triton X-100 mapped to kinase domain II/III and specifically to serine 390 of
      MEKK3 and valine 384 of MEKK2, residues immediately N-terminal to the active site
      lysine. Mutation of serine 390 of MEKK3 to a valine (as is found in MEKK2)
      conferred catalytic activity to MEKK3 in Triton X-100 whereas the reciprocal
      alteration of valine 384 of MEKK2 to a serine conferred lack of activity in
      Triton X-100 to MEKK2. Search of the protein database identified only three
      kinases, MEKK3, Pbs2p and Dd-PKI, with a serine or threonine at this site. The
      presence of a serine or threonine adjacent to the active site lysine in protein
      kinases is rare and, in MEKK3, results in detergent instability.

PMID- 11343803
TI  - Sulfide is an efficient iron releasing agent for mammalian ferritins.
AB  - The most prominent role of mammalian ferritins is to provide an extensive iron
      buffering capacity to cells. The large ferritin iron stores can be mobilized in
      vitro, but the functional relevance of the most efficient iron releasing agents
      remains elusive. Sulfide is a strongly reducing chemical generated by a series of
      enzymes. In the presence of limited amounts of sulfide a continuous rate of iron
      release from ferritin was observed and a majority of the protein iron core was
      recovered in solution. The rate constants for iron efflux triggered by several
      reducing or chelating compounds have been measured and compared. Although not as
      efficient as reduced flavins, sulfide displayed kinetic parameters which suggest
      a potential physiological role for the chalcogenide in converting the iron
      storage protein into apoferritin. To further probe the relevance of sulfide in
      the mobilization of iron, several enzymes, such as NifS, rhodanese, or sulfite
      reductase generating reduced forms of sulfur by different mechanisms, have been
      assayed for their ability to catalyze the release of iron from ferritin. The
      results show that full reduction of sulfur into sulfide is needed to deplete iron
      from ferritin. These reactions suggest links between sulfur metabolism and
      intracellular iron homeostasis.

PMID- 11343804
TI  - Treatment and prevention of acute respiratory failure: physiological basis.
AB  - Acute respiratory failure is caused by many factors and remains one of the most
      common reasons for admission to the intensive care unit (ICU). In all cases of
      acute respiratory failure, there is a shortage of surfactant at the alveolar
      level. This deficit of surfactant leads to an increase in alveolar surface
      tension that increases the retraction forces of the lung, leading to end
      expiratory alveolar collapse, finally resulting in respiratory dysfunction, which
      includes hypoxemia, low lung compliance, increase of intrapulmonary shunts, low
      functional residual capacity, atelectasis, and pulmonary edema. The goal of the
      treatment and prevention of acute respiratory failure is therefore based on the
      following three main items: re-opening the collapsed alveolar units; preserving
      the active surfactant component in the remaining functional alveolar units, and
      preventing end-expiratory collapse. The following strategies can be used to
      prevent and/or treat acute respiratory failure: counterbalancing the retraction
      forces of the lung by applying sufficiently high external pressures; and/or
      decreasing the surface tension at the air-liquid interface by means of exogenous
      surfactant, and/or eliminating the air-liquid interface by filling the lung with
      perfluorocarbons. By applying these therapeutic strategies in routine clinical
      practice, we should achieve a reduction in the mortality rate of patients
      suffering from acute respiratory failure.

PMID- 11343805
TI  - Trichomonas vaginalis has two fibronectin-like iron-regulated genes.
AB  - BACKGROUND: Trichomonas vaginalis, a protozoan parasite of the human urogenital
      tract, interacts with fibronectin (FN), a glycoprotein of the extracellular
      matrix. We, therefore, attempted to identify genes of this eukaryote encoding FN
      binding proteins. METHODS: A cDNA clone, C1, representing an incomplete gene was
      obtained from an expression library based on its FN-binding ability and was
      characterized. The full-length 378-bp gene encoding a 14.8-kDa protein of 125
      amino acids was obtained. RESULTS: The amino acid sequences revealed homology
      with the type III-14 repeat of the heparin-binding domain at the carboxyl
      terminal end of FN. This fibronectin-like protein gene, flp1, was single copy in
      all the T. vaginalis isolates examined. Levels of flp1 transcript were elevated
      in cells grown under low-iron conditions. Another low-iron-regulated gene, flp2,
      with 70 and 67.5% identity to flp1 at the nucleotide and amino acid levels,
      respectively, was recovered from the trichomonad genome. Both flp1 and flp2 had
      consensus Inr promoter-like elements immediately adjacent to the start codon.
      flp2 also contained an additional Inr element followed by an ATG 24-bp within the
      gene. CONCLUSIONS: Unlike flp2, the flp1 gene had AU-rich destabilizing elements
      in the 3'-untranslated region (UTR).

PMID- 11343806
TI  - CD40 ligand expression in mycobacterium bovis BCG infection and its regulation by
      cytokines: a direct role of interleukin 12.
AB  - BACKGROUND: Activation and clonal expansion of T cells require not only the
      recognition of processed antigen on the surface of the antigen-presenting cell
      (APC) by T-cell receptor (TCR), but also involve co-stimulatory signals that are
      provided by the simultaneous engagement of cell surface molecules expressed by
      both the APC and the T cell. Interaction between CD40 and its ligand (CD40L) is
      known to mediate host immune response and T-cell-mediated effector functions in
      mycobacterial infections in mice. In this work, we investigated the capacity of
      Mycobacterium bovis (M. bovis) BCG to induce the expression of CD40L on human T
      cells. METHODS: Human cells were obtained from healthy adults by centrifugation
      using Ficoll/Hypaque. Cells (1 x 10(6)) were incubated in RPMI medium with BCG.
      After incubation at 37 degrees C in 5% CO(2) atmosphere for 40 h, cells were
      collected and double-stained with anti-CD40L-PE and anti-CD4-FITC or anti-CD8
      FITC mAb. The quantification of positively stained population was based on
      samples stained with isotype control antibodies analyzed on a FACScan. RESULTS:
      M. bovis BCG stimulation induced a significant amount of CD40L expression on CD4+
      T cells, while CD40L was not significantly detected on human CD8+ T cells. The
      highest CD40L expression on BCG-activated T cells in synergism with interleukin
      12 endogenous occurred after a 40-h cell culture with a dose of 10 microg/mL of
      BCG (84.86 +/- 11.77; mean +/- standard deviation [SD]). This CD40L expression on
      BCG-activated human T cells was significantly inhibited by anti-IL-12 mAb (5.08
      +/- 1.7; mean +/- SD). In contrast, anti-IFN-gamma and anti-IL-2 mAb did not have
      an important role in this expression. CONCLUSIONS: These results indicate that
      the capacity of BCG to induce CD40L expression on human cells represents a novel
      mechanism underlying the regulation of cellular responses against tuberculosis.
      Furthermore, the results showed a direct role of IL-12 to enhance the expression
      of CD40L on BCG-activated human cells.

PMID- 11343807
TI  - Effect of sensitized macrophages in transplantable sarcoma in mice. synergistic
      effect of hyperimmunized serum, sensitized spleen cells and macrophages in tumor
      transplantation.
AB  - BACKGROUND: Immunosuppression cannot develop tumors by itself. It may induce
      tumors under appropriate conditions and may accelerate tumor development which
      may be reversed by sensitized spleen cells. This study concerns the effect of
      sensitized macrophages in murine-transplantable sarcomas by a combination of
      hyperimmune serum, sensitized spleen cells and macrophages. METHODS: The main
      technique adopted was intraperitoneal (ip) injection of 2 mL of 10% protease
      peptone broth, followed 2 days later by inoculation into the peritoneum with 10
      mL Hank isotonic solution. The cells from the pooled peritoneal fluid were tested
      by dye exclusion test to ascertain the percentage of live cells. They were tried
      in whole body-irradiated mice with a combination of immune serum and sensitized
      spleen cells to ascertain whether a suppression of growth of solid tumors could
      be achieved when subcutaneously (sc) administered with the previously mentioned
      combinations. RESULTS: The addition of immunomacrophages from transplanted tumor
      bearing mice significantly suppressed the growth of subcutaneous solid tumors
      when the number of tumor cells was kept constant. A change in number of
      immunomacrophages from hyperimmunized mice at a ratio of 4:l showed a direct
      relationship in suppression of tumor growth. Experiments were initiated in which
      tumor cells were injected sc and peritoneal macrophages were injected either
      intravenously (iv) or ip. Experiments were then initiated to prove that cell-to
      cell contact is essential for tumor suppression. In experiments in which tumor
      cells were administered sc and macrophages injected either iv or ip, a
      significant immunosuppressive effect was not shown, thus also indicating that
      regardless of which, cell-to-cell contact is an absolutely essential factor
      involved in tumor suppression. A combination of hyperimmune serum and macrophages
      was found to act synergistically. Macrophages and hyperimmune serum at a lesser
      proportion did not suppress tumor growth. Sensitized macrophages and spleen cells
      together significantly suppressed tumor growth in a pure isogenic strain of
      irradiated mice. The sensitized macrophages injected iv prolonged the survival
      period and retarded tumor growth. CONCLUSIONS: Tumor suppression by macrophages
      was found to be due to its contact with tumor cells that enables the effective
      transfer of immunity. Hyperimmune serum and other cells (macrophages, spleen
      lymphocytes) act synergistically toward each other and prolong the survival
      period.

PMID- 11343808
TI  - In vitro effects of albendazole and its metabolites on the cell proliferation
      kinetics and micronuclei frequency of stimulated human lymphocytes.
AB  - BACKGROUND: Albendazole (ABZ) is an antiparasitic drug used for the treatment of
      several helminthiases. After its oral administration, this compound is
      metabolized to sulfoxide (SOABZ) and sulfone (SO(2)ABZ), SOABZ being the active
      metabolite. The antiparasitic activity of ABZ has been associated with its
      capacity to bind with tubulin, altering microtubule formation. Although some
      studies indicate that ABZ modified microtubule structure in host cells, data
      concerning the consequences of this phenomenon in human cells are scant. METHODS:
      In this study we evaluated the effects of ABZ and its metabolites on cell
      proliferation, as well as on the frequency of micronucleated cells in cultured
      human lymphocytes. RESULTS: ABZ and SOABZ arrested cell proliferation in
      metaphase and increased the frequency of micronuclei in treated lymphocytes.
      Contrariwise, SO(2)ABZ, the inactive metabolite, did not produce any significant
      effect. CONCLUSIONS: The formation of micronuclei may ultimately result in
      aneuploidy induction, an effect that could have severe consequences in humans.
      However, the doses of ABZ and SOABZ at which these effects were observed are
      several orders of magnitude higher than those found in the plasma of treated
      individuals. Because there are other mechanisms by which aneuploidy can be
      induced at even lower doses than micronuclei, i.e., chromosome nondisjunction, it
      is necessary to evaluate this effect in exposed individuals.

PMID- 11343809
TI  - Myotonic dystrophy protein kinase (DMPK) gene expression in lymphocytes of
      patients with myotonic dystrophy.
AB  - BACKGROUND: Myotonic dystrophy (DM) is an autosomal dominant neuromuscular
      disorder with defects in many tissues, including skeletal muscle myotonia,
      progressive myopathy, and abnormalities in heart, brain, and endocrine systems.
      It is associated with a trinucleotide repeat occurring in the 3' (UTR)
      untranslated region of the myotonic dystrophy protein kinase (DMPK) gene. Several
      studies have been carried out to determine DMPK gene expression in muscle and non
      muscle tissues. METHODS: DMPK gene expression was determined in lymphocytes of
      adult-onset patients with DM and normal controls. To quantitate total locus
      expression as well as allele-specific mRNA levels, semiquantitative RT-PCR assay
      was used. Allele-specific expression was analyzed using a Bpm1 polymorphism
      located at exon 10 of the DMPK gene. RESULTS: In heterozygous patients with DM,
      we observed a fourfold difference between mRNA levels produced by the Bpm1
      undigested allele (187 bp) compared to the Bpm1-digested allele (136 bp). By
      using (CTG) trinucleotide (with cytosine, thymine, and guanine) expansion
      polymorphism, it was shown that the down-regulated allele corresponds to the
      mutant allele. Interestingly, the reduction in the mutant allele-transcript
      levels is compensated by an increase of the wild-type allele, yielding no
      significant differences in total locus mRNA amount between patients and normal
      individuals. CONCLUSIONS: These results suggest that the expression of the two
      alleles at the DMPK locus in lymphocytes is coordinated. The reduction in mutant
      allele transcript levels is compensated by an increase in wild-type allele mRNA
      levels.

PMID- 11343811
TI  - Primary hypertrophic osteoarthropathy: clinical, radiologic, and scintigraphic
      characteristics.
AB  - BACKGROUND: Our aim was to establish clinical and imaging characteristics of
      primary hypertrophic osteoarthropathy (PHO). METHODS: A group of 76 patients (71
      men and 5 women) with primary hypertrophic osteoarthropathy was examined.
      Extensive history and status of the locomotor system were determined in all
      patients. Radiologic and scintigraphic examinations of the bones, thermography,
      capillaroscopy, gastroscopy, and histologic analysis were also performed.
      RESULTS: Family history was positive in all 55 patients (100%) summoned for a
      check-up. Finger clubbing of the hands and feet as well as positive Schamroth
      test were found in all patients, while hyperhydrosis was found in 65 (85.5%),
      seborrhea in 39 (51%), and involvement of the joints in 52 (68.5%) patients.
      Histologic analysis in 18 (23.7%) patients predominantly showed periarticular
      edema and moderate cellular activity. Periostosis of the long bones was also
      found in all patients, while scintigraphy, performed in 44 patients, was positive
      in 18 (33.5%) patients in the active phase of the disease. Thermography,
      performed in 10 patients, ranged from hypothermia to thermal amputation of feet
      and hands. Capillaroscopy of hands and feet in 47 (61.8%) patients showed changes
      in small blood vessels. Gastroscopy indicated abnormalities (ulcer and
      hypertrophic gastritis) in 21 patients (27.6%). CONCLUSIONS: PHO has special
      clinical and radiographic manifestations (finger clubbing and periostosis of the
      long bones) that are associated with some minor manifestations. Development of
      the disease is gradual (to 20 years) and requires a special diagnostic
      assessment.

PMID- 11343810
TI  - Serum immunoglobulins, IL-1beta, IL-2, and IFN-gamma gamma level in patients with
      lymphedema treated with ortho-beta-hydroxy-ethyl rutosides (HR).
AB  - BACKGROUND: This investigation was undertaken to study the clinical
      characteristics and the humoral immune pattern in lymphedema patients undergoing
      O-beta-hydroxy-ethyl rutoside therapy. METHODS: A complete physical examination
      was performed on 27 lymphedema patients (postmastectomy and postphlebitis) and 17
      healthy controls. Clinical evaluation of affected limbs was carried out
      concerning swelling, circumference, mobility, and tissue tension, while
      immunologic studies consisted of serum IgG, IgA, IgM, C3, and 1-glycoprotein,
      interleukin-1 beta, interleukin-2, and IFN-gamma levels. Immunoglobulins and
      alpha-1-acid glycoprotein were assessed by radial immune diffusion (RID) and
      interleukin levels, by ELISA (R & D Systems Kits, R & D Systems, Minneapolis, MN,
      USA). On admission, patients received O-beta-hydroxy-ethyl rutosides (HR) 1 g/day
      during a period of 6 months. RESULTS: These demonstrated several clinical,
      functional, and immunologic alterations in lymphedema patients. HR treatment
      produced a remarkable reduction in swelling, circumference, and tissue tension,
      and an improvement in mobility. In addition, edema was also diminished. The
      immunologic profile observed in untreated lymphedema patients is as follows: IgG
      and alpha-1-acid glycoprotein concentration were slightly diminished in
      comparison with the control group, reaching normal levels after therapy. The
      difference among these values was significant (p <0.001). Contrariwise, normal C3
      values were detected with a significant posttreatment decrease (p <0.001). Normal
      serum IgA and IgM levels in patients with lymphedema before and after HR
      treatment are shown, and are similar to those of the control group. In addition,
      Il-1beta and IL-2 values are higher in relation to control values (p <0.01),
      attaining normal concentration after therapy. Normal levels of IFN-gamma were
      found in lymphedema patients, and there was no difference with control values.
      The concentration of this cytokine was not influenced by HR. IL-1beta and IL-2
      concentrations were higher than in controls (p <0.001). Values reached normal
      levels after therapy (p <0.01). CONCLUSIONS: Diverse clinical and immunologic
      alterations were evidenced in lymphedema patients. The immunoglobulin profile and
      IL-1beta and IL-2 levels were also modified. After HR treatment, their
      improvement was reflected by the favorable effect regarding the previously
      mentioned alterations. O-beta-hydroxy-ethyl rutosides are effective both
      clinically and immunologically.

PMID- 11343812
TI  - Dopaminergic modulation of human bronchial tone.
AB  - BACKGROUND: Dopamine exerts inhibitory and excitatory effects on different
      systems. Its effect on human bronchial tone is controversial. It has been
      reported that dopamine has no acute effect on human airways from normal subjects
      or those with asthma background. However, inhaled or infused dopamine decreased
      histamine-induced bronchoconstriction in both normal and asthmatic subjects.
      METHODS: We examined the possible modulating effect of dopamine on bronchial
      diameter by administering inhaled dopamine and the DA(2) dopaminergic blocker
      metoclopramide (MTC) to subjects with various degrees of bronchial tone. We
      examined 50 volunteers. Arterial blood pressure and heart rate were determined in
      each subject. By means of spirometry, we measured forced vital capacity (FVC),
      forced expiratory volume in the first second (FEV(1)), maximal forced expiratory
      flow (FEF(max)), and forced expiratory flow at 50% of vital capacity (FEF(50)),
      before and after each treatment. By inhalation with a nebulizer, we administered
      the following: a) dopamine (0.5 microg/kg/min) to 10 healthy subjects, 10
      subjects with asthma without acute bronchospasm (AWAB), and nine subjects with
      acute asthma attack (AAA), and b) intravenous (i.v.) metoclopramide (7
      microg/kg/min) was administered to 10 healthy subjects and 11 subjects with AWAB.
      For ethical reasons, MTC was not used in subjects with acute asthma attack. Non
      parametric Wilcoxon test for paired samples, ANOVA test, and Bonferroni multiple
      comparison test were performed. Inhaled dopamine increased FEV(1) and FVC,
      FEF(max), and FEF(50) in the AAA group, but there were no modifications in the
      healthy group or in the AWAB group. Metoclopramide did not induce changes in
      respiratory parameters in healthy individuals or in those with AWAB. CONCLUSIONS:
      Inhaled dopamine is able to induce bronchodilatation when the bronchial tone is
      already increased by acute asthma attack but did not modify the resting bronchial
      tone in normal subjects or in asthmatics without acute bronchospasm.
      Additionally, DA(2) blockade with metoclopramide did not modify resting bronchial
      tone. Dopamine exerts a modulatory effect on the bronchial tone of human airways
      depending on the degree of preexisting tone.

PMID- 11343813
TI  - Efficacy and safety of repeated postoperative administration of intramuscular
      diclofenac sodium in the treatment of post-cesarean section pain: a double-blind
      study.
AB  - BACKGROUND: Analgesic drugs, either opioids or non-opioids, are required and
      useful for controlling postoperative pain after cesarean section. METHODS: The
      analgesic and opioid-sparing effects of repeated intramuscular (i.m.) injections
      of 75 mg of diclofenac sodium given immediately after the experiencing of pain
      following cesarean section under general anesthesia were studied and compared
      with placebo in a double-blind trial. One hundred twenty patients 18-40 years of
      age undergoing elective lower segment cesarean section were treated with either
      75 mg diclofenac sodium i.m. (60 patients) or identical placebo (60 patients),
      once patients awakened from anesthesia and experienced wound pain. Their initial
      responses to either treatment during the first hour after administration of
      medications were studied. The analgesic, sedative, and opioid-sparing effects of
      the medications were also studied during the next 48 h. Side effects including
      uterine relaxation and bleeding were compared between patients administered
      placebo and diclofenac. RESULTS: Results showed that 55/60 patients showed
      significant pain relief within the first 1 h after administration of diclofenac
      sodium and their mean pain score decreased from 7.09 +/- 1.06 to 0.85 +/- 0.8 (p
      <0.05). Within the same period, 10/60 patients responded to placebo injections
      and mean pain score decreased from 6.6 +/- 0.96 to 0.8 +/- 0.78 (p <0.05). During
      the first postoperative 48 h, 45 patients showed complete pain relief with use of
      diclofenac alone while 15 patients required 2,800 mg of pethidine in addition to
      diclofenac treatment. All patients using placebo required pethidine injection;
      the total amount of pethidine used was 22,700 mg per 48 h. Verbal scores for
      sedation were lower in patients treated with diclofenac than in patients treated
      with placebo at 6 and 12 h postoperatively (p <0.05). There were no significant
      differences in the proportions of patients who required oxytocin infusion due to
      uterine relaxation in the diclofenac-treated and the placebo-treated groups (7/60
      vs. 12/60, p >0.05). CONCLUSIONS: It might be concluded that repeated i.m.
      injections of 75 mg diclofenac sodium (maximum two injections per day) could
      relieve postoperative pain after cesarean section and significantly reduce opioid
      analgesic requirements without significant effects on uterine relaxation or
      bleeding during the first postoperative 48 h.

PMID- 11343814
TI  - Role of sensory innervation variations for wrist block anesthesia.
AB  - BACKGROUND: A variety of anesthesia techniques for hand surgery have been
      suggested. METHODS: Cases of single peripheral nerve block and incomplete wrist
      block failures are analyzed and compared with a group of patients with complete
      wrist block. RESULTS: According to the results of our study, in 825 cases there
      was a 15% rate of documented failures of incomplete wrist block, most probably
      due to anomalous sensory innervation. CONCLUSIONS: This clinical observation is
      in agreement with many published studies on neural anatomy and supports the use
      of complete wrist block for hand surgery.

PMID- 11343815
TI  - Antimicrobial resistance from enterococci in a pediatric hospital. Plasmids in
      Enterococcus faecalis isolates with high-level gentamicin and streptomycin
      resistance.
AB  - BACKGROUND: Enterococcus spp. is an important nosocomial and community-acquired
      pathogen. Recent studies have documented the increasing importance of this
      pathogen in children, particularly in the hospital setting. Our objective in this
      study was to report the frequency of antimicrobial resistance in enterococci and
      to determine the characteristics of high-level gentamicin resistance (HLGR)
      plasmids in Enterococcus faecalis clinical isolates. METHODS: Two hundred eighty
      nine enterococcal isolates were collected during an 18-month period from a
      tertiary-care pediatric hospital in Mexico City. Isolates were screened for
      antibiotic resistance, including HLGR. High-level, gentamicin-resistant E.
      faecalis strains were selected for pulsed-field electrophoresis (PFGE) typing and
      plasmid analysis. Transferability of resistance markers was carried out using
      filter matings. RESULTS: Seventy-six percent of isolates were E. faecalis, 10%
      were E. avium, 5.2% E. faecium, 5.2% E. raffinossus, 1.38% E. malodoratus, 0.6%
      E. hirae, and 0.6% E. casseliflavus. Antimicrobial resistance was ampicillin and
      penicillin 29%, imipenem 17%, and vancomycin 3%, HLGR 5%. The following 15 high
      level, gentamicin-resistant isolates were identified: six E. faecalis; four E.
      avium; three E. faecium, and two E. casseliflavus. Five of the six E. faecalis
      isolates were different by PFGE and transferred gentamicin and streptomycin
      resistance on filter membranes. Transfer frequencies ranged from 8.2 x 10(-4) to
      6.92 x 10(-5) transconjugants/recipient cell. The plasmid content of donors and
      transconjugants were homogeneous (one plasmid of 47 kb). CONCLUSIONS: In this
      pediatric hospital, antimicrobial resistance in Enterococcus spp. is common.
      Frequency of high-level, gentamicin-resistant strains is low. Mechanism of HLGR
      appears to be due to a single plasmid dissemination.

PMID- 11343816
TI  - Acute gastroenteritis associated with rotavirus in adults.
AB  - BACKGROUND: Rotavirus (RV) is an important cause of acute infectious diarrhea in
      children all over the world. In adults, RV infection tends to be subclinical;
      however, outbreaks of gastroenteritis have been reported in emergency situations
      and in closed communities. The aim of this study was to characterize
      electrophoretically and antigenically the strains of rotavirus that caused acute
      gastroenteritis in adults and correlate them with the clinical manifestations.
      METHODS: A laboratory-based survey was carried out in which fecal samples from 44
      patients over 18 years of age with acute gastroenteritis were studied.
      Polyacrylamide gels electrophoresis and immunoenzymatic assay with specific
      antibodies to group A rotavirus, serotypes G1-4, P1A, and P1B were carried out on
      all the samples. RESULTS: Twenty-eight (63.63%) of the 44 samples were positive
      for group A rotavirus. Of these, 19 (68%) had long pattern and nine (32%) short
      pattern. Of all positive samples, 15 (54%) were serotype G1, seven (25%) were G2,
      two (7%) were G4, and four (14%) had no monoclonal reaction; all were serotype
      P1A. Among the patients with RV infection, 13 (46.4%) required hospitalization
      and the remaining 15 (53.6%) showed moderate symptoms. CONCLUSIONS: The strains
      that infected the adults were electrophoretically and antigenically the same as
      those that infected infants in Merida, Yucatan over the last 10 years. No
      relationship between the severity of the symptoms and any specific serotype was
      found.

PMID- 11343817
TI  - Lidocaine as antagonist of scorpion poison toxicity from Centruroides limpidus
      limpidus.
AB  - BACKGROUND: In Mexico, scorpion poisoning is a health problem because the poison
      has beta toxins that affect sodium channel activation. Lidocaine decreases ion
      permeability across the sodium channel acting in the opposite manner. The aim of
      this work is to determine whether lidocaine antagonized the toxic effect of the
      crude poison of Centruroides limpidus limpidus. METHODS: One half the lethal dose
      of the crude poison was determined alone and in the presence of different doses
      of lidocaine. Experiments with crude poison at LD(50) and crude poison plus
      lidocaine were carried out after 30, 90, and 180 min of poison inoculation; lung,
      heart, and brain were obtained for histopathologic analysis. RESULTS: Lidocaine
      (7 mg/kg dose) increased LD(50) of crude poison (2.95 +/- 0.22 to 6.68 +/- 0.25,
      p <0.001). Intraalveolar hemorrhage at 30, 90, and 180 min, myocardial edema, and
      brain congestion at 90 min were significantly reduced (p <0.05). CONCLUSIONS:
      Lidocaine exerts a protective effect against toxicity of the crude poison of
      Centruroides limpidus limpidus, probably by its antagonist activity on the sodium
      channel.

PMID- 11343819
TI  - Different tonic regulation of neuronal activity in the rat dorsal raphe and
      medial prefrontal cortex via 5-HT(1A) receptors.
AB  - It has been established that 5-HT(1A) receptors are expressed both
      presynaptically as autoreceptors by 5-HT containing neurones, and
      postsynaptically by a variety of other neurones. Activation of either
      somatodendritic 5-HT(1A) autoreceptors or postsynaptic 5-HT(1A) receptors induces
      hyperpolarisation and inhibition of action potential discharge of the neurones,
      but it is unclear whether 5-HT(1A) receptors are under a general tonic influence
      by 5-HT. In the present study, using single unit recordings from both
      anesthetized and non-anesthetized rats, we show that the activity of neurones in
      the medial prefrontal cortex is not altered by systemic administration of the
      selective 5-HT(1A) receptor antagonist, WAY 100635. In contrast, WAY 100635
      increased the firing rate of 5-HT neurones in the dorsal raphe nucleus. Our
      findings indicate a tonic activation of presynaptic somatodendritic but not
      postsynaptic cortical 5-HT(1A) receptors.

PMID- 11343820
TI  - Fast and slow neurons in the nucleus of the basal optic root in pigeons.
AB  - The nucleus of the basal optic root (nBOR) is involved in the generation of the
      optokinetic response. Previous studies showed that most nBOR neurons exhibit
      direction-selectivity in response to largefield motion. We investigated the
      responses of pigeon nBOR neurons to drifting sine wave gratings of varying
      spatial and temporal frequency (SF,TF). Two groups of neurons were revealed. The
      first group preferred gratings of low SF (mean, 0.07 cycles per degree (cpd)) and
      high TF (mean, 0.76 Hz) ('fast' stimuli). The second group preferred gratings of
      high SF (mean, 0.56 cpd) and lower TF (mean, 0.33 Hz) ('slow' stimuli). Previous
      studies have demonstrated fast and slow neurons in pretectal nucleus lentiformis
      mesencephali, which is also involved in the generation of the optokinetic
      response.

PMID- 11343821
TI  - Low dose aspirin attenuates escape/avoidance behavior, but does not reduce
      mechanical hyperalgesia in a rodent model of inflammatory pain.
AB  - The present experiment examined the effect of aspirin on the escape/avoidance
      behavioral response to a mechanical stimulus (476 mN von Frey monofilament) in
      the place escape avoidance paradigm (PEAP) following subcutaneous administration
      of carrageenan (CARR). Forty-one male Sprague-Dawley rats received subcutaneous
      injection of CARR or saline in the left hindpaw and 3 1/2 h later were
      administered aspirin (0, 50 or 150 mg/kg). Thirty minutes later, animals were
      tested in the PEAP and then the mechanical paw withdrawal threshold was measured.
      Compared with Saline vehicle-treated controls, all CARR-treated animals displayed
      hyperalgesia, as reflected by enhanced responding to mechanical stimulation
      applied to the CARR-injected paw. Mechanical hyperalgesia was significantly
      reduced by the pre-treatment of 150 mg/kg, but not 50 mg/kg aspirin. In the PEAP,
      CARR vehicle-treated animals avoided a preferred location of the test chamber
      that was associated with mechanical stimulation of the hyperalgesic paw. The
      shift from a preferred dark side of the chamber to the light side was attenuated
      by pre-treatment with both doses of aspirin (50 and 150 mg/kg). The lack of anti
      hyperalgesia and avoidance behavior with 50 mg/kg aspirin suggests a decrease in
      the aversive nature of mechanical stimulation of the afflicted paw. It is
      suggested that the mechanisms underlying the affective/motivational dimension of
      nociception (escape/avoidance) can be dissociated from the processing of
      nociceptive information related to withdrawal responding.

PMID- 11343822
TI  - The effect of thiopental on glutamate metabolism in mouse cerebellar astrocytes
      in vitro.
AB  - The effect of thiopental on [U-(13)C]glutamate metabolism was studied in
      cerebellar astrocytes from mice using (13)C magnetic resonance spectroscopy. The
      cells were incubated with 0.5 mM [U-(13)C]glutamate for 2 h in the presence of 1
      mM thiopental and 1 mM thiopental plus 0.2 mM gammaamino butyric acid (GABA).
      Labeled glutamate, glutamine, aspartate and glutathione were observed in cell
      extracts, and glutamine, aspartate and lactate in the media. Not only uniformly
      labeled glutamate was present in the medium, but also glutamate derived from the
      tricarboxylic acid (TCA) cycle. In the presence of thiopental, the amount of
      unlabeled glucose and [U-(13)C]glutamate removed from the medium was unchanged.
      This is in contrast to previous results obtained in cortical astrocytes, showing
      cellular heterogeneity. The concentrations of [1,2,3-(13)C]glutamate and [U
      (13)C]glutamine were increased in the cell extracts, but unchanged in the medium,
      indicating an increased synthesis and an unchanged exchange or release. It should
      be noted that [U-(13)C]lactate is formed from [U-(13)C]glutamate via the TCA
      cycle and is released to the medium. In the presence of thiopental less [U
      (13)C]lactate was observed in the medium. GABA had no influence on the effects of
      thiopental on cerebellar astrocytes.

PMID- 11343823
TI  - Odor responses and spontaneous oscillatory activity in tentacular nerves of the
      terrestrial slug, Limax marginatus.
AB  - We studied the neural oscillatory activity in the peripheral olfactory system of
      the tentacles in the terrestrial slug, Limax marginatus, by extracellular
      recording. Recordings from the cut-ends of the inferior tentacular nerves
      connected to the inferior tentacular ganglia and sensory epithelia showed
      spontaneous oscillatory activity at frequencies of 0.1-30 Hz. This spontaneous
      activity was dominated by the 0.6-6 Hz band. Ethanol odor stimulation decreased
      the amplitude in the 0.6-6 Hz band and increased those in the 6-15 and 15-30 Hz
      bands. Antagonists of the gamma-aminobutyric acid (GABA) receptor, bicuculline
      and picrotoxin, resulted in suppression of spontaneous activity and modulated the
      odor response in the 0.6-6 Hz band. Our results indicate the involvement of GABA
      mediated oscillatory activity in the tentacular nerves in the olfactory
      processing in molluscs.

PMID- 11343824
TI  - Total neuronal numbers of rat lumbosacral primary afferent neurons do not change
      with age.
AB  - Total cell numbers and neuronal diameters of L6 and S1 dorsal root ganglia, which
      provide a sensory innervation to pelvic viscera were determined in young adult (3
      months-old) and compared to those in old (24-months-old) male rats. Two methods
      of cell counting, serial (section) reconstructions and total profile counting,
      were used in this study. Our data showed that the total number of L6 and S1
      dorsal root ganglia (DRG) cells and their diameters remain essentially constant
      from 3 to 24 months of age. These results have shown that rat DRG cell numbers do
      not change during adult life and that neurogenesis of DRG cells in adult rats or
      neuronal cell death in aged rats cannot be supported. These findings are also
      consistent with other data supporting the maintenance of pelvic sensory
      innervation in old age.

PMID- 11343825
TI  - Decrease in motor cortical excitability in human subjects after sleep
      deprivation.
AB  - The effect of sleep deprivation on human motor cortical excitability was
      investigated by evaluating the changes in motor evoked potentials from the thenar
      eminence muscles of the right hand in seven subjects. Motor threshold, motor
      evoked potential amplitude, silent period, intracortical inhibition,
      intracortical facilitation and F wave were studied. Recordings were performed
      every 6 h during the day-time (from 09.00 to 21.00 h) and every 3 h during the
      night-time (from 21.00 to 09.00 h). Significant increases in motor threshold,
      intracortical inhibition and silent period were noted in the recordings during
      the night associated with a return to baseline values in the morning. No
      significant changes were observed in any of the other parameters. Enhancement of
      intracortical motor inhibition is suggested to explain the effect of sleep
      deprivation.

PMID- 11343826
TI  - Synthetic superoxide dismutase/catalase mimetics reduce oxidative stress and
      prolong survival in a mouse amyotrophic lateral sclerosis model.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder that
      causes motoneuron degeneration, paralysis and death. Mutations in Cu, Zn
      superoxide dismutase (SOD1) are one cause of this disease. It is widely suspected
      that increased reactive oxidative species (ROS) is involved in motoneuron
      degeneration but whether such an involvement plays a role in ALS progression in
      vivo is uncertain. We treated mice expressing human mutant SOD1 G93A with EUK-8
      and EUK-134, two synthetic SOD/catalase mimetics that have shown efficacy in
      several animal models of human diseases. These treatments reduced levels of
      oxidative stress and prolonged survival. The results suggest that oxidative
      stress plays an active role in ALS and illustrate the potential for treatment
      strategies aimed specifically against ROS.

PMID- 11343827
TI  - Amyloid beta protein deposition in patients with frontotemporal lobar
      degeneration: relationship to age and apolipoprotein E genotype.
AB  - Amyloid beta protein (Abeta) deposition was investigated in the frontal cortex of
      54 autopsy cases of frontotemporal lobar degeneration (FTLD) using methenamine
      silver staining, and immunohistochemistry employing the monoclonal end-specific
      antibodies BC05 and BA27 to visualize deposits containing Abeta(42(43)) and
      Abeta(40), respectively. Abeta was detected in 14 (26%) patients, nearly always
      in the form of diffuse Abeta(42(43)) containing plaques though some cored,
      neuritic plaques with trace amounts of Abeta(40) were occasionally seen. The 14
      patients showing Abeta deposits were significantly older at onset of illness than
      those 40 patients without Abeta. It was only possible to genotype 46/54 cases, 16
      of whom bore at least one copy of the Apolipoprotein E (APOE) epsilon4 allele,
      giving an allele frequency of 20%. Possession of APOE epsilon4 allele was
      significantly associated with deposition of Abeta such that 10/16 epsilon4 allele
      bearers had Abeta deposits. Eight of these ten patients showed only mild to
      moderate amounts of Abeta, but in two patients, one homozygous and one
      heterozygous for epsilon4 allele, there was extensive neuritic plaque and
      neurofibrillary tangle formation. In contrast, only few non-epsilon4 allele
      bearers (4/30) showed minor Abeta deposits. When stratifying for APOE epsilon4
      allele, both bearers and non-bearers of epsilon4 allele with Abeta deposits had a
      significantly later age at onset than their respective groups without Abeta
      deposits. We conclude that the likelihood of Abeta deposition, as a secondary and
      coincidental feature unrelated to the primary pathological process, within the
      brains of individuals with FTLD will be high if patients have a sufficiently late
      onset of illness or happen to be a bearer of the APOE epsilon4 allele. Indeed
      9/14 patients with Abeta deposits studied here had an onset of illness after 55
      years of age and bore APOE epsilon4 allele.

PMID- 11343828
TI  - Delayed cell death in neonatal mouse hippocampus from hypoxia-ischemia is neither
      apoptotic nor necrotic.
AB  - Hypoxic-ischemic (HI) injury in neonatal mice is associated with significant cell
      loss in hippocampus, striatum and deep layers of the cortex. The pattern of cell
      death in hippocampus after a moderate focal ischemic-global hypoxic insult is
      studied through morphologic changes in dying neurons at both the light and
      ultrastructural levels. Light microscopy at 24 h showed a number of injured
      neurons, as evidenced by dark, round, condensed nuclei, primarily in CA1 through
      CA3. Nuclei appeared punctate and cytoplasm vacuolated. Electron microscopy
      revealed that the punctate appearance of the nuclei corresponded to clumped
      chromatin. At 7 days after HI, injured neurons were shrunken and had a uniformly
      dark, angular appearance. While dying cells had an appearance consistent with
      apoptosis on light microscopy, cells were neither necrotic nor apoptotic at the
      ultrastructural level.

PMID- 11343829
TI  - Recombinant core protein fragment of phosphacan, a brain specific chondroitin
      sulfate proteoglycan, promote excitotoxic cell death of cultured rat hippocampal
      neurons.
AB  - We investigated the role of phosphacan, a chondroitin sulfate proteoglycan that
      is constitutively expressed in the adult hippocampus, and recombinant core
      proteins of phosphacan in excitotoxic cell death of primary cultured rat
      hippocampal neurons. Phosphacan had no significant effect on excitotoxic neuronal
      death. Surprisingly, one of three recombinant proteins corresponding to N
      terminal portions of phosphacan core protein dramatically promoted excitotoxic
      neuronal death. Moreover, the recombinant protein induced cell death of rat
      hippocampal neurons, even when neurons were not exposed to glutamate. These
      results suggest that proteolytic degradation of phosphacan and resultant core
      protein fragments may contribute to neuronal degeneration of hippocampal neurons
      in various neuropathological conditions.

PMID- 11343830
TI  - Fractal correlation of initial trajectory dynamics vanishes at the movement end
      point in human rapid goal-directed movements.
AB  - Many researchers have investigated the variability of discrete goal-directed
      movements. However, a possible time-dependent property for them has been ignored.
      We investigated the time-dependent property of the kinematic variability in human
      rapid goal-directed movements by using fractal analysis. The variability of the
      peak acceleration had fractal time correlation characterized by a non-negligible
      frequency-spectral exponent (beta=0.3). This beta value was reduced at the peak
      velocity (beta=0.2) and nearly reached zero at the peak movement amplitude,
      indicating that the variability became white noise with no time correlation. A
      similar result was observed in the progress of the positional trajectory. The
      functional significance of this phenomenon for the goal-directed task demand is
      discussed.

PMID- 11343831
TI  - Synergistic apoptosis induced by bacterial endotoxin lipopolysaccharide and high
      glucose in rat microglia.
AB  - The present study investigates whether bacterial lipopolysaccharide (LPS) in the
      presence of increased levels of glucose induced synergistic cytotoxicity in
      primary cultured microglia. Significant cytotoxicity was only observed while the
      concentrations of LPS were increased to 10 microg/ml. D-glucose concentration
      dependently (25-125 mM) generated cytotoxicity. Synergistic apoptosis of
      microglia was seen by LPS in the presence of increased levels of D-glucose. This
      synergistic cytotoxicity was attenuated by the use of superoxide dimutase and
      catalase, suggesting the involvement of oxidative free radicals. Collectively,
      the present results suggest that increased ambient levels of glucose rendered
      microglia vulnerable to LPS insults, and led to a synergistic apoptosis. The
      findings here may be important in certain patho-physiological implications in
      which hyperglycemia exacerbated the ambient functions contributed by microglia,
      and may provide new insight into a novel therapeutic intervention.

PMID- 11343832
TI  - Expression of PEPT2 peptide transporter mRNA and protein in glial cells of rat
      dorsal root ganglia.
AB  - The peptide-transporter PEPT2 mediates electrogenic uphill transport of di- and
      tripeptides, selected peptidomimetics and delta aminolevulinic acid. The
      transporter was cloned from rat central nervous tissue recently and its mRNA was
      localized to astrocytes. In the present studies the expression of PEPT2-protein
      and -mRNA in rat dorsal root ganglia was investigated. Immunohistochemistry
      revealed PEPT2-immunoreactivity in satellite glial cells surrounding the
      ganglionic neurons. There was no expression in neuronal cells. In-situ
      hybridization studies colocalized the expression of PEPT2-mRNA to satellite
      cells. This is the first report on the expression of PEPT2-protein in the
      peripheral nervous system where PEPT2 may serve as uptake system for products of
      protein degradation, for removal of biologically active short-chain peptides and
      non-peptides such as delta aminolevulinic acid.

PMID- 11343833
TI  - Excitotoxic injury stimulates pro-drug-induced 7-chlorokynurenate formation in
      the rat striatum in vivo.
AB  - Peripheral administration of L-4-chlorokynurenine (4-Cl-KYN), which is
      enzymatically converted in astrocytes to form the glycine(B) receptor antagonist
      7-chlorokynurenic acid (7-Cl-KYNA), has been shown to provide neuroprotection
      against excitotoxic damage. The present study was designed to examine the
      metabolic fate of 4-Cl-KYN after systemic injection, and to study its brain
      uptake and subsequent transamination during the acute phase following an
      excitotoxic insult. To this end, adult rats received intrastriatal injections of
      vehicle (1 microl) or quinolinic acid (QUIN) (240 nmol/1 microl), and were
      administered 50 mg/kg 4-Cl-KYN (intraperitoneally) immediately after surgery.
      After 90 and 180 min, 7-Cl-KYNA concentrations in the vehicle-injected striatum
      were 54+/-13 and 16+/-2 nM, respectively. The contralateral, QUIN-injected
      striatum contained 212+/-39 and 97+/-27 nM 7-Cl-KYNA, respectively. This injury
      induced increase was accompanied by slightly higher 4-Cl-KYN levels in the QUIN
      treated striatum, indicating that better pro-drug availability in part accounts
      for the enhanced 7-Cl-KYNA formation. These data demonstrate that systemic 4-Cl
      KYN application, by targeting reactive glial cells during the early, reversible
      stage of excitotoxic neurodegeneration, produces disproportionately large amounts
      of the neuroprotectant 7-Cl-KYNA at the site of the emerging lesion.

PMID- 11343834
TI  - Survival and neurite outgrowth of rat cortical neurons in three-dimensional
      agarose and collagen gel matrices.
AB  - To better understand interactions between neurons and extracellular matrix
      equivalents, embryonic day-18 rat cortical neurons were immobilized and
      maintained in culture for up to 24 days in agarose and type I collagen gels.
      Using live/dead staining, neuronal cultures in low density collagen gel lasted at
      least 3 weeks. At 14 days, over 50% of immobilized cells in collagen gel were
      found viable while in low density agarose gel no cells survived. In situ cell
      death detection showed that most, if not all, dead cells in either of the gels
      underwent apoptosis. The collagen-trapped neurons exhibited normal neuronal
      polarity and developed long neurites, estimated at over 500 microm. The results
      suggest that collagen, because it is a major extracellular matrix constituent,
      suppresses apoptosis and provides a suitable substrate for neuronal survival and
      differentiation.

PMID- 11343835
TI  - The role of dopamine in methylene blue-mediated inhibition of estradiol benzoate
      induced anterior pituitary hyperplasia in rats.
AB  - Recently, we demonstrated that methylene blue partially inhibited estradiol
      benzoate-induced anterior pituitary hyperplasia in rats. Since central
      dopaminergic systems participate in the regulation of estrogen-induced anterior
      pituitary growth and tumor transformation, this study examined whether a 3-week
      treatment with methylene blue could affect anterior pituitary levels of dopamine
      (DA), dihydroxyphenylalanine (DOPA), and dihydroxyphenylacetic acid and dopamine
      (D-2) receptors in male rats. Compared to controls, methylene blue significantly
      decreased anterior pituitary weight, increased basal anterior pituitary DA
      levels, and inhibited estradiol benzoate-induced decreases in anterior pituitary
      DA concentrations. Furthermore, we found that methylene blue alone decreased
      anterior pituitary D-2 receptor number. Methylene blue given in combination with
      estradiol benzoate partially inhibited estradiol benzoate-induced anterior
      pituitary growth and estradiol benzoate-induced increases in D-2 receptor number.
      Estradiol benzoate-treated rats had significantly lower anterior pituitary DOPA
      accumulation after intraperitoneal administration of 3,4-hydroxybenzyl-hydrazine
      dihydrochloride (NSD-1015), an irreversible inhibitor of L-aromatic amino acid
      decarboxylase whereas methylene blue did not affect anterior pituitary DOPA
      accumulation when compared to controls. Methylene blue decreased anterior
      pituitary prolactin levels and inhibited increases in anterior pituitary
      prolactin after estradiol benzoate administration. The present results suggest
      that anterior pituitary DA may play an important role in estrogen-induced
      anterior pituitary hyperplasia and tumor formation and that antioxidant drugs
      such as methylene blue may attenuate estrogen-induced pituitary growth. This may
      occur via increases in anterior pituitary DA levels associated with down
      regulation of anterior pituitary D-2 receptors.

PMID- 11343836
TI  - In vivo protection of a water-soluble derivative of vitamin E, Trolox, against
      methylmercury-intoxication in the rat.
AB  - Methylmercury (MeHg) is a well-known neurotoxicant. MeHg-intoxication causes a
      disturbance in mitochondrial energy metabolism in skeletal muscle and apoptosis
      in cerebellum. We report the first in vivo effectiveness of antioxidant Trolox (6
      hydroxy-2,5,7,8-tetramethylchroman-2-carhoxylic acid), a water soluble vitamin E
      analog, against the MeHg-induced cellular responses. Treatment with Trolox (6
      hydroxy-2.5,7,8-tetramethylchroman-2-carboxylic acid) clearly protects MeHg
      treated rat skeletal muscle against the decrease in mitochondrial electron
      transport system enzyme activities despite the retention of MeHg. Tdt-mediated
      dUTP nick-end-labeling method clarified that Trolox is effective for protecting
      cerebellum from MeHg-induced apoptosis. These data indicate that MeHg-mediated
      oxidative stress plays an important role in the in vivo pathological process of
      MeHg intoxication. Trolox may prevent some of clinical manifestations of MeHg
      intoxication in humans.

PMID- 11343837
TI  - The --491 TT apolipoprotein E promoter polymorphism is associated with reduced
      risk for sporadic Alzheimer's disease.
AB  - Homozygosity for the A allele of the -491 A/T apolipoprotein E (APOE) promoter
      polymorphism has recently been reported to be associated with sporadic
      Alzheimer's disease (AD). Two hundred and fifty one patients with AD and an equal
      number of controls derived from the same region in a Spanish population, were
      genotyped for -491 A/T and epsilon2/epsilon3/epsilon4 APOE polymorphisms. We did
      not detect an elevated -491 AA genotype frequency when comparing AD cases to
      controls. In contrast, persons homozygous for the T allele were at a
      significantly reduced risk of AD (odds ratio of 0.10, P=0.006). Multiple logistic
      regression analysis indicated that the -491 TT polymorphism added information on
      the risk of AD which was independent of that of the APOE epsilon4 allele.

PMID- 11343838
TI  - Genetic and environmental determinants of interferon-tau secretion by in vivo-
      and in vitro-derived bovine blastocysts.
AB  - Several experiments were conducted to assess the effects of genotype and various
      culture media on interferon-tau secretion by in vitro-derived bovine blastocysts
      and to compare these values with interferon released by blastocysts flushed from
      superovulated cows. In experiment 1, oocytes were inseminated with semen from
      three different bulls. While paternal genotype had no effect on cleavage rate,
      the size or hatching ability of blastocysts, it was a significant determinant of
      the embryo's ability to develop to the blastocyst stage and of subsequent
      interferon-tau secretion. In the second experiment, embryos were cultured in
      synthetic oviductal fluid containing either polyvinyl alcohol, bovine serum
      albumin or fetal bovine serum. While there was no effect of supplement on the
      percentage of embryos developing to the blastocyst stage, blastocysts which
      formed in medium with polyvinyl alcohol had significantly fewer cells, were older
      at blastocyst formation and produced significantly more interferon-tau. In the
      third experiment, embryos were cultured to the blastocyst stage in either TCM199
      alone or in co-culture with buffalo rat liver, bovine oviductal or bovine uterine
      epithelial cells. Culture with oviductal or buffalo rat liver cells increased
      blastocyst cell number, although secretion of interferon-tau was not affected. In
      the final experiment, bovine blastocysts were flushed from superovulated cows on
      Day 7 following insemination. Overall, secretion of interferon-tau by in vivo
      produced blastocysts did not differ from that of age-matched blastocysts produced
      in vitro.

PMID- 11343839
TI  - Long-term follicular dynamics and biochemical characteristics of dominant
      follicles in dairy cows subjected to acute heat stress.
AB  - The objective of this study was to examine the quality of successive dominant
      follicles (DFs) after induced heat stress. Non-lactating dairy cows expressing
      estrus at normal intervals were allocated randomly to heat stress (HS; n=8) and
      control (C; n=8) groups. Cows received GnRH (100 microg, i.m.) on Day 0, a
      progesterone CIDR-B device on Day 4 and prostaglandin (PGF(2alpha); 25mg, i.m.)
      on Day 7 upon removal of the CIDR device. The DF and follicles >5mm were
      aspirated on Day 8, and GnRH (100 microg) injected following aspiration, to
      initiate a new follicular wave. In this manner, a DF was aspirated every 8 days
      (one "follicular cycle") for 10 cycles. After the first follicular cycle, HS cows
      were placed in environmental chambers for 7 days during the second follicular
      cycle (8h per day at 43.3 degrees C set point and 16h per day at 24 degrees C for
      4 days, and 8h per day at 43.3 degrees C set point and 16h per day at 32.2
      degrees C set point for 3 days; relative humidity, 40%) and thereafter maintained
      outdoors with control cows at a mean ambient temperature (18.5 degrees C; range
      12.7-26 degrees C). Rectal temperature increased (P<0.001) in HS as compared with
      C cows (39.28+/-0.01 degrees C versus 38.78+/-0.01 degrees C). Concentrations of
      estradiol (E(2); 1662+/-189 versus 1493+/-188ng/ml) and progesterone (P(4);
      44.7+/-5 versus 54.1+/-5.1ng/ml) in follicular fluid (FF) of DF did not differ
      between C and HS treatments, respectively. Total FF protein concentration was
      greater (P<0.05) in HS (99.7+/-2.3mg/ml) than in C (92.7+/-2.3mg/ml). Heat shock
      protein 90 (Hsp 90) in FF was not altered by heat stress. IGF-II ligand blots
      were conducted with FF samples (n=79) from four HS and four C cows. There was a
      predominance of IGFBP-3 in 76 of 79 FF samples, indicating healthy follicular
      status, and only three FF samples had the lower molecular weight IGFBP-2
      indicative of a poor quality follicle. Plasma P(4) and E(2) concentrations did
      not differ between C and HS groups. The number of class 1 and 3 follicles
      increased during and just after heat stress, but the number of class 2 follicles
      did not differ between C and HS cows. Heat stress appeared to induce a decrease
      in follicular dominance, but GnRH-induced follicular cycles resulted in
      development of healthy preovulatory follicles in both groups.

PMID- 11343840
TI  - Progesterone metabolism in ovariectomised non-lactating Holstein-Friesian cows
      treated with progesterone with two levels of feed intake.
AB  - The goal of this study was to measure the effects of level of feeding and the
      form of progesterone (P4) administration on the concentrations and yields of
      faecal P4 metabolites relative to differences in plasma P4 concentrations in non
      lactating cows. Six non-lactating Holstein-Friesian cows were ovariectomised
      (OVX) and allocated to two groups: (i) P4 by subcutaneous injection (P4-s.c.,
      n=3); and (ii) P4 administration per vaginum (P4-p.v., n=3). Each cow in the P4
      s.c. group was injected subcutaneously once daily with 200mg P4. Each cow in the
      P4-p.v. group had a CIDR device inserted for 11 days when it was removed and
      replaced with a second device for further 11 days. Cows were fed a ration
      containing lucerne (33%) and oaten (66%) chaff at a maintenance level (M) in two
      portions in the first period of the study, and at a half-maintenance (1/2M) level
      during the second period. Chromic oxide capsules (Cr(2)O(3)) were administered
      twice daily to allow faecal output (FO) to be estimated. Plasma P4 and faecal P4
      metabolites (FP4M; 20-oxo-pregnanes, 20alpha- and 20beta-OH-pregnanes) were
      measured during the treatment period. Daily FO declined after reducing the M diet
      to 1/2M (4.77 versus 2.61kg; P<0.01), whereas plasma P4 concentrations increased
      in the P4-s.c. group (4.2 versus 6.2ng/ml; P<0.05), but not in the P4-p.v. group
      (0.9 versus 1.0ng/ml; P>0.2). The mass of P4 released from a CIDR device during
      each 11-day period (M or 1/2M) was similar (0.66 versus 0.63g). Faecal 20-oxo
      pregnanes (20-oxo-) concentrations were not affected by day or level of feeding,
      whereas faecal 20alpha-OH (20alpha-) and 20beta-OH (20beta-) concentrations were
      increased with the 1/2M diet in the P4-s.c. group (4.3 versus 5.6 microg/gDM; 2.2
      versus 5.6 microg/gDM, respectively; P<0.05), but not in the P4-p.v. group (2.3
      versus 2.7 microg/gDM; 1.7 versus 3.04 microg/gDM P>0.05). These changes in
      concentration only partly compensated for the reduced FO with the 1/2M diets as
      daily yields of FP4M (20-oxo- and 20alpha-) were greater during the M diet period
      (20-oxo-: 6.9 versus 4.1 microg/gDM; 2.7 versus 1.5 microg/gDM, for P4-s.c. and
      P4-p.v. groups, respectively; P<0.05, 20alpha-: 19.9 versus 13.6 microg/gDM; 10.9
      versus 6.6 microg/gDM for P4-s.c. and P4-p.v. groups, respectively; P<0.05). The
      level of feeding and the route of P4 administration had key roles in controlling
      P4 concentrations in blood and daily FP4M yield.

PMID- 11343841
TI  - Sustained testicular atrophy in bulls actively immunized against GnRH: potential
      to control carcase characteristics.
AB  - The objectives were to determine whether active immunization against
      gonadotrophin releasing hormone (GnRH) induced a long-term suppression of
      testicular function in bulls, and to ascertain the effects of immunization
      against GnRH on carcase and meat quality characteristics. In experiment 1, 6
      month-old Zebu bulls were assigned to: control (n=25), no treatment; immunized
      (n=31), immunized against GnRH at 0 and 4 months (anti-GnRH(2)), with a sub-set
      of bulls (n=17) immunized again at 10 months (anti-GnRH(3)). After the second
      immunization, testicular growth ceased for 2 months in 14/31 (45%) bulls and for
      at least 6 months in 17/31 (55%) bulls. Among the latter bulls (anti-GnRH(3)) the
      testes did not grow for >1 year after the third immunization in 5/17 (30%) bulls.
      In experiment 2, 22-month-old Zebu bulls were assigned to: control (n=14), no
      treatment; immunized (n=17), immunized against GnRH at 0, 2 and 4 weeks. The
      testes decreased (P<0.05) in size for 2 months after immunization in 11/17 (65%)
      bulls and then re-initiated growth, whilst in 6/17 (35%) bulls the testes
      continued to decrease in size for 4 months and did not re-initiate growth for 1
      year. At slaughter, the latter immunocastrated bulls had carcase and meat quality
      characteristics the same as contemporary bulls that had been castrated before
      puberty. The findings demonstrated that active immunization against GnRH can
      induce a long-term suppression of testicular function in a proportion of bulls.
      Also, when bulls are immunocastrated after puberty, carcase and meat quality
      traits change from those typical of entire bulls to traits that are
      characteristic of long-term castrated bulls.

PMID- 11343842
TI  - Ovulation rate and distribution in the thoroughbred mare, as determined by
      ultrasonic scanning: the effect of age.
AB  - Ovarian activity was monitored in 2181 oestrous cycles from 1136 thoroughbred
      brood mares to accurately determine overall ovulation rate, the relative
      distribution of ovulations between left and right ovary, whether mare age had an
      effect on these parameters and whether ovulation pattern in one cycle affected
      the pattern within the next. Ultrasonic scanning was used in preference to rectal
      palpation and slaughterhouse material due to its greater accuracy. Mare's ages
      ranged from 3 to 22 years. The results obtained indicated a similar incidence of
      ovulation occurring on the right (49.5% of all ovulations) or left ovary (50.5%).
      Multiple ovulations (MO) occurred in 22.4% of oestrous cycles. Significantly
      (P<0.01), more double ovulations (DO) were bilateral (57.2%) than unilateral
      (42.8%); 20.7% were unilateral right and 22.1% were unilateral left. There were
      828 mares grouped into six age groups: A (3-5 years), B (6-8 years), C (9-11
      years), D (12-14 years), E (15-18 years), F (18-22 years). The distribution of
      ovulation between the left and right ovary was not affected by age group, but
      significant association (P<0.01) was evident between age and MO. Group A had 15%
      of cycles resulting in MO compared to 19.4, 24.6, 25.8, 28.6 and 35.1% in groups
      B-F, respectively. A significant (P<0.01) association between MO in successive
      cycles was also demonstrated, with a greater chance (P<0.05) of successive single
      ovulations (SO) being on alternate ovaries. There was no significant
      repeatability of the classification of DO in one cycle compared to the next. We
      conclude that: (i) the mare is a symmetrical ovulator; (ii) 22.4% of cycles yield
      MO (ovulation rate 1.23); (iii) this MO incidence increased (P<0.01) with age;
      (iv) the exhibition of MO in one cycle was linked to an increased probability
      (P<0.01) of a MO occurring at the next one and (v) SO in one ovary was more
      likely (P<0.05) to be followed by a SO on the alternate ovary during the next
      cycle.

PMID- 11343843
TI  - Factors affecting follicular population, oocyte yield and quality in camels
      (Camelus dromedarius) ovary with special reference to maturation time in vitro.
AB  - Three experiments were conducted to study a series of factors affecting in vitro
      reproductive parameters in camels. In Experiment 1, the effect of season and
      presence of a corpus luteum (CL) on ovarian follicular populations, oocyte yield
      and quality was studied using a total of 252 and 208 ovaries collected during the
      breeding and non-breeding season, respectively. Small, medium, large and the
      total number of ovarian follicles, oocyte yield and quality were measured. In
      Experiment 2, the effect of methods of oocyte retrieval and needle gauge on
      oocyte yield and quality was evaluated with oocytes recovered using slicing and
      aspiration with 18-, 19- or 20-gauge needle. Oocytes were evaluated
      microscopically and classified into three categories. The objective of Experiment
      3 was to identify the optimum time for oocyte maturation in the dromedary camel.
      Oocytes were cultured in CR1aa medium at 38.5 degrees C under 5% CO(2) for 24,
      32, 36, 48 and 72h. Maturation was calculated as the percentage of cumulus
      expansion and oocytes reaching metaphase II (MII). The number of small, medium,
      large and the total number of ovarian follicles were higher (P<0.01) during the
      breeding than non-breeding season. The recovery of total number of oocytes and
      Category I oocytes were also greater (P<0.01) during the breeding season. Ovaries
      without a CL possessed significantly (P<0.01) more ovarian follicles and more
      (P<0.05) small and large follicles. The total number of oocytes and Category I
      oocytes were also greater (P<0.01) in ovaries without CL. Slicing of camel
      ovaries increased (P<0.01) the yield of oocytes as compared to aspiration. The
      aspiration of follicles using a 20-gauge needle had greater yields of the total
      number of oocytes and Category I oocytes than when using 19- (P<0.05) and 18
      gauge needle (P<0.01). The culture of camel oocytes for 36h produced higher
      (P<0.01) percentages of cumulus expansion and oocytes at MII. Increasing culture
      times up to 48 or 72h increased (P<0.01) the percentage of degenerated oocytes.
      In conclusion, the growth and development of ovarian follicles in the camel as
      well as yields of Category I oocyte were greater during the breeding season.
      Slicing or aspirations using a 20-gauge needle yielded greater numbers of total
      and Category I oocytes. Finally, maturation of oocytes in CR1aa medium for 36h
      produced higher percentages of cumulus expansion and oocytes at MII stage.

PMID- 11343844
TI  - Prediction of gestational age by ultrasonic fetometry in llamas (Lama glama) and
      alpacas (Lama pacos).
AB  - Fetal biparietal diameter (BPD) and thorax height (TH) were measured by
      ultrasound during intrauterine growth in pregnant llamas (Lama glama) and alpacas
      (Lama pacos). The goal was to establish representative curves that allows
      estimation of gestational age (GA) from real-time ultrasonic measurements of
      these fetal structures at any stage of gestation. Llamas and alpacas were mated
      under controlled conditions. Ultrasound exams were conducted to determine
      pregnancy status 1 month later. Measurements of fetal BPD and TH were conducted
      from the second month of pregnancy until term. Observation and assessment of
      fetal TH was difficult during the last 3 months of pregnancy, specially in
      llamas. Regression curves were calculated from the data as a function of GA, with
      the best fit represented by the following equations: llama GA=(BPD
      0.002399)43.02293,r=0.98,P<0.001; llama GA=(TH-0.07137)46.94485, r=0.95,P<0.001;
      alpaca GA=(BPD-0.11376)47.23287, r=0.98,P<0.001; alpaca GA=(TH-0.36436)52.87663,
      r=0.96,P<0.001, where GA was measured in days and BPD and TH in centimeters.
      Results indicate that ultrasonic measurement of these fetal biometric variables
      constitute a valuable tool to estimate GA at any stage of pregnancy in these
      domestic South American camelids.

PMID- 11343845
TI  - Erythropoietin mRNA expression in pig embryos.
AB  - To address whether altered erythropoietin (EPO) synthesis might be involved in
      prenatal pig mortality, studies were conducted to measure porcine embryonic EPO
      mRNA expression during early gestation (days 24-40). Three pig models differing
      in embryonic survival from days 24-40 were investigated: intact white crossbred
      gilts (INT), white crossbred gilts that were unilaterally hysterectomized
      ovariectomized before puberty and whose pregnant uterus constituted a crowded
      environment (UHO), and prolific, intact Meishan gilts (ME). A partial cDNA for
      porcine EPO, developed via reverse transcription and polymerase chain reaction
      procedures was used to generate a 32P-labeled probe for use in Northern analyses.
      In an initial study, embryonic liver EPO mRNA was greatest on day 24, decreased
      by day 30 (P<0.01), and was barely detectable by day 40. EPO mRNA expression was
      not influenced by pig model. Placental EPO mRNA expression was detectable in only
      4 of 53 placentae examined. In a second study at day 35 of gestation, embryonic
      liver EPO mRNA expression was measured in the same three pig models and in two
      embryos of divergent weights from each gilt. Meishan embryos had lower (P<0.01)
      plasma immunoassayable EPO concentrations (P=0.04) and higher survival rates
      (87+/-2.7%) at day 35 than did white crossbred embryos (75+/-5%). Liver EPO mRNA
      expression did not differ among animal models, nor did plasma EPO or tissue EPO
      mRNA expression differ between large and small embryos. There was no apparent
      relationship between embryonic development, measured as embryonic and placental
      size, and plasma EPO concentrations or liver EPO mRNA expression. These results
      indicate that at the gestational ages examined, the embryonic liver is one source
      of plasma erythropoietin and suggest that at the ages sampled, EPO is not a
      limiting factor in embryonic development.

PMID- 11343846
TI  - Synchronization of porcine fetal fibroblast cells with topoisomerase-inhibitor
      hoechst 33342.
AB  - Proper synchronization of donor nuclei has been shown to have a major influence
      on the developmental potential of nuclear transfer embryos. In the present study,
      a protocol was established to synchronize porcine fetal fibroblasts in the G2
      stage of the cell cycle. Cell cycle analyses were performed by flow cytometry.
      Cells were pre-synchronized by serum deprivation or aphidicoline-treatment; then
      incubated in medium containing 0.1 microg/ml Hoechst 33342 (H342). The
      fluorochrome H342 has been shown to be a topoisomerase-inhibitor that can inhibit
      progression through the cell cycle. There was no significant difference in the
      percentage of fibroblasts in G2/M whether cells were pre-synchronized in medium
      supplemented with 0.1% serum for 48h or 0.5% serum for 6 days. Compared with
      controls, pre-synchronization in early S-phase before incubation in H342
      increased the proportion of G2/M fibroblasts; also an increase from 0 and 6
      versus 12h culture in complete medium before incubation in H342 resulted in an
      increased percentage of cells in G2/M at the end of the synchronization period
      (9.3 and 13.1% versus 33.7%; P<0.001). Neither an increase in the concentration
      of H342 (0.1-1.0 microg/ml) nor a longer exposure time (12h versus 18h versus
      24h) increased the proportion of G2/M fibroblasts. The protocol established in
      this study arrested porcine fibroblasts reversibly in the G2/M-stage and is
      therefore suitable to provide synchronized cells for nuclear transfer
      experiments.

PMID- 11343847
TI  - Alteration of gonadotrophin and steroid hormone release, and of ovarian function
      by a GnRH antagonist in gilts.
AB  - This study examined the impact of the gonadotrophin-releasing hormone (GnRH)
      antagonist Antarelix on LH, FSH, ovarian steroid hormone secretion, follicular
      development and pituitary response to LHRH in cycling gilts. Oestrous cycle of 24
      Landrace gilts was synchronised with Regumate (for 15 days) followed by 800 IU
      PMSG 24h later. In experiment 1, Antarelix (n=6 gilts) was injected i.v. (0.5mg
      per injection) twice daily on four consecutive days from day 3 to 6 (day 0=last
      day of Regumate feeding). Control gilts (n=6) received saline. Blood was sampled
      daily, and every 20 min for 6h on days 2, 4, 6, 8 and 10. In experiment 2, gilts
      (n=12) were assigned to the following treatments: Antarelix; Antarelix + 50
      microg LHRH on day 4; Antarelix + 150 microg LHRH on day 4 or control, 50 microg
      LHRH only on day 4. Blood samples were collected daily and every 20 min for 6h on
      days 2, 4 and 6 to assess LH pulsatility. Ovarian follicular development was
      evaluated at slaughter. Antarelix suppressed (P<0.05) serum LH concentrations.
      The amount of LH released on days 4-9 (experiment 1) was 8.80 versus 36.54 ngml(
      1) (S.E.M.=6.54). The pattern of FSH, and the preovulatory oestradiol rise was
      not affected by GnRH antagonist. Suppression of LH resulted in a failure (P<0.05)
      of postovulatory progesterone secretion. Exogenous LHRH (experiment 2) induced a
      preovulatory-like LH peak, however in Antarelix treated gilts the LH surge
      started earlier and its duration was less compared to controls (P<0.01).
      Furthermore, the amount of LH released from day 4 to 5 was lower (P<0.01) in
      Antarelix, Antarelix + 50 and Antarelix + 150 treated animals compared to
      controls. No differences were estimated in the number of LH pulses between days
      and treatment. Pulsatile FSH was not affected by treatment. Mean basal LH levels
      were lower (P<0.05) after antagonist treatment compared to controls. Antarelix
      blocked the preovulatory LH surge and ovulation, but the effects of Antarelix
      were reduced by exogenous LHRH treatment. The development of follicles larger
      than 4mm was suppressed (P<0.05) by antagonist treatment. In conclusion,
      Antarelix treatment during the follicular phase blocked preovulatory LH surge,
      while FSH and oestradiol secretion were not affected. Antarelix failed to alter
      pulsatile LH and FSH secretor or pituitary responsiveness to LHRH during the
      preovulatory period.

PMID- 11343848
TI  - A method of age estimation using Raman microspectrometry imaging of the human
      dentin.
AB  - The aim of this work is to establish a correlation between ageing and Raman
      spectra imaging of human teeth. Raman spectrum of an analysed sample is
      characteristic of its chemical components. By exploring the different dentinal
      areas on each tooth, we sought to find a correlation between noticeable
      variability on Raman spectra and the stages of dentinal evolution with advancing
      age. A study on 30 teeth analysed by Raman microspectrometry was used to select
      predictors of age, and it allowed us to determine a regression formula, with age
      as a dependent variable. Our data were computed by means of a statistical method
      called partial least squares (PLS) regression. This method was specially adapted
      for this kind of situation, where we have numerous predictors and relatively few
      observations. The regression formula was performed on a test sample of four more
      teeth, and we obtained a correct age estimation, with a mean error of more or
      less than 5 years. The main benefits of this method was a minimal and non
      destructive tooth preparation, which led to an efficient age prediction, for any
      age group.

PMID- 11343849
TI  - Primary study of vascular endothelial growth factor immunohistochemical staining
      in the diagnosis of early acute myocardial ischemia.
AB  - The expression of vascular endothelial growth factor (VEGF) in the model of rat
      early acute myocardial ischemia was studied by Strept-Avidin-Biotin-Peroxidase
      Complex (SABC) immunohistochemical staining. After ligating the anterior
      descending branch of the left coronary artery, an initial rapid (30min) positive
      expression of VEGF in myocardial ischemic areas was observed, the intensity of
      positive expression of VEGF increased with the continuation of myocardial
      ischemia. After 5h infarction, the strongly positive myocytes of SABC-VEGF
      staining were predominantly limited to perimyocardial infarction areas. No
      positive expression of VEGF was found in the control group. These findings
      suggested that SABC-VEGF method could give a sensitive, specific, simple and
      objective morphologic evidence to the diagnosis of sudden cardiac death caused by
      acute early myocardial ischemia.

PMID- 11343850
TI  - Comparative analysis of differences by gender in sudden infant death syndrome in
      Hungary and Japan.
AB  - We examined the sex ratio in sudden infant death syndrome (SIDS) cases in
      Hungary, in Tokyo and Japan between 1985 and 1996. From all the infant death
      cases in Hungary 395 (240 male, 155 female) were SIDS (odds ratio (OR)=1.179,
      with 95% confidence interval (CI)=0.961, 1.446), in Japan 4348 (2550 male, 1798
      female) were SIDS (OR=1.145, with 95% CI=1.076, 1.218) and in Tokyo 307 (178
      male, 129 female) were SIDS (OR=1.128, with 95% CI=0.894, 1.423). Male infants
      showed a significantly higher birth rate than females. The male infants are more
      vulnerable (p<0.005), however, higher mortality among male infants should not be
      considered a characteristic feature for SIDS.

PMID- 11343851
TI  - Technical note: latent fingermarks, colloidal gold and multimetal deposition
      (MMD). Optimisation of the method.
AB  - Operational details and optimisation of the colloidal gold or multimetal
      deposition technique (MMD) for the detection of latent fingermarks on non porous
      and porous surfaces demonstrate the power of the method. Control of particulate
      size, pH, reagent, handling are shown to be essential. A difficult case example
      illustrates the potential of MMD.

PMID- 11343852
TI  - Postmortem biochemical examination of synovial fluid--a preliminary study.
AB  - Vitreous humor chemistry is used for postmortem analysis since serum values of
      many components are thought to be reflected in vitreous humor and to be stable
      for a prolonged postmortem interval (pmi). A similar isolated compartment to
      vitreous humor is synovial fluid which up to now was hardly used for postmortem
      chemistry. The aim of the present examination was to compare the values of
      various analytes in both fluid compartments to get first hints for the
      reliability of the examination of synovial fluid. Therefore, in 74 cases of
      sudden death both fluids were taken and analysed for natrium, potassium, calcium,
      chloride, urea, creatinine, and glucose. The results show that the examination of
      synovial fluid as compared to vitreous humor is a reliable method to get hints on
      the premortal metabolic status since most analytes are stable postmortem. The
      range of all values is comparable in both fluids. The time course of glucose
      concentrations and, much more important, potassium concentrations is nearly
      similar. If no vitreous humor is available synovial fluid may be used with all
      precautions in diagnosis known from vitreous humor.

PMID- 11343853
TI  - Forced oral opening for cadavers with rigor mortis: two approaches for the
      myotomy on the temporal muscles.
AB  - Forensic dentistry plays an essential role in personal identification procedures.
      An adequate interincisal space of cadavers with rigor mortis is required to
      obtain detailed dental findings. We have developed intraoral and two directional
      approaches, for myotomy of the temporal muscles. The intraoral approach, in which
      the temporalis was dissected with scissors inserted via an intraoral incision,
      was adopted for elderly cadavers, females and emaciated or exhausted bodies, and
      had a merit of no incision on the face. The two directional approach, in which
      myotomy was performed with thread-wire saw from behind and with scissors via the
      intraoral incision, was designed for male muscular youths. Both approaches were
      effective to obtain a desired degree of an interincisal opening without facial
      damage.

PMID- 11343854
TI  - Analysis of total mercury in human tissues prepared by microwave decomposition
      using a hydride generator system coupled to an atomic absorption spectrometer.
AB  - A fast and efficient procedure has been developed for the analysis of total
      mercury in human tissues and blood using a hydride vapor generator system coupled
      to an atomic absorption spectrometer (HVG-AA). Tissue and blood samples were
      digested in a pressurized microwave decomposition system and the digest diluted
      prior to formation of free mercury vapor and analysis by atomic absorption.
      Recovery studies performed on 10 spiked/unspiked pairs of human liver and on 10
      spiked/unspiked pairs of human blood samples yielded average recoveries of 99.7%
      (CV=0.4%) and 101.2% (CV=0.5%), respectively. The method detection limit for
      liver and blood was 50 microg Hg/kg and 12.5 microg Hg/l, respectively. The
      "normal" concentrations of mercury in human liver and blood are 33-490 microg
      Hg/kg and 0.6-59 microg Hg/l, respectively [1]. This method is able to determine
      mercury poisoning levels and may also be applied to detect mercury near the lower
      levels of these "normal" ranges, using the standard addition method approach.

PMID- 11343855
TI  - The expression of excitatory amino acid transporter 2 (EAAT2) in forensic autopsy
      cases.
AB  - Glutamate is the major excitatory neurotransmitter and the greater part of this
      amino acid is removed from the synaptic cleft by excitatory amino acid
      transporter 2 (EAAT2) located on perisynaptic astrocytes. Recently, it was
      reported that the EAAT2 protein content changed in rats following forebrain
      ischemia and administration of methamphetamine. We planned to demonstrate the
      immunohistochemical distribution of EAAT2 in the human brain and discuss the
      significance of its pathophysiological roles. Thirty-two cases were used from
      forensic autopsies. The tissues were sampled from the cerebral cortex, striatum
      and hippocampus. The distribution of EAAT2 was difficult to identify in cases of
      electrical fatalities. However, continuous and extensive staining of EAAT2 was
      observed in cases of death from hypothermia. In almost all asphyxia death, we
      were able to observe a weak stain of EAAT2. In case of solvent abuse, EAAT2
      staining was continuous and extensive as in the cases of hypothermia, and patchy
      negative zones were mixed. This study clearly showed the differences in EAAT2
      localization according to the cause of death. These findings suggested that the
      differences in EAAT2 staining depended on the cause and course
      (pathophysiological conditions) of death.

PMID- 11343856
TI  - Neck injuries as a reconstructive parameter in car-to-pedestrian accidents.
AB  - The study has assessed the usefulness of injuries to the ligamentous, muscular
      and vascular neck structures for deducing about the presumable location of a
      pedestrian in relation to a motor vehicle at the moment of collision. The
      localisation of haemorrhagic suffusions in the lower insertions of the scalene
      (mainly) and sternocleidomastoid muscles has shown a correlation with the
      direction of the inertia force. No correlation has been observed between the
      direction of impact and damages to the cervical vascular bundles and the
      localisation of haemorrhagic suffusions in the upper insertions of the nape
      muscles. In some cases, injuries to the ligaments of the cervical vertebrae made
      up the complex characteristic of the direction of acting forces. The injuries of
      soft tissues and ligaments can, thus, facilitate the deductions about the
      direction of impact. However, the type of a car involved in the accident and the
      possibility that these injuries resulted from direct head or neck trauma should
      be considered.

PMID- 11343857
TI  - Ankle joint injuries as a reconstruction parameter in car-to-pedestrian
      accidents.
AB  - The study has assessed the usefulness of ankle joint injuries for deducing about
      the presumable location of a pedestrian in relation to a motor vehicle at the
      moment of collision. A statistically significant correlation was found between
      the direction of impact and the mechanism of ankle joint injuries. Such injuries
      were found in 113 of 317 pedestrian, fatal victims of road traffic accidents
      (36%). In the cases of impacts on the medial surface of the lower limb, the
      injuries associated with the supination mechanism were six times more frequent
      than the injuries associated with the pronation mechanism, while in the group of
      impacts on the limbs from the lateral side those connected with the pronation
      mechanism were four times more frequent. In victims hit from the back, the
      injuries connected with the plantarflexion mechanism were found almost four times
      more frequent than the dorsiflexion mechanism and in victims hit from the front
      in three of the five damaged joints the dorsiflexion component was observed
      (without any plantarflexion case). Less frequent "pronation injuries" in the
      limbs hit from the medial side and "supination injuries" in the limbs hit from
      the lateral side as well as "dorsiflexion injuries" in victims hit from the back
      predominantly occurred in impacts to the pelvic area, i.e. resulting from
      collisions with a van or lorry. Injuries of upper ankle joints are, thus, useful
      for reconstructing the presumable location of the pedestrian in relation to the
      vehicle at the moment of collision, especially, when the vehicle involved in the
      accident is known.

PMID- 11343858
TI  - Age-at-death diagnosis and determination of life-history parameters by
      incremental lines in human dental cementum as an identification aid.
AB  - Incremental lines in acellular extrinsic fiber cementum of 91 roots from 80
      freshly extracted teeth have been investigated for a verification of the
      suitability of pathological teeth for a valid age-at-death diagnosis. Independent
      from tooth type, the accuracy of histological age-at-death diagnosis is clearly a
      function of a tooth's pathological state. Various periodontal diseases lead to a
      reduced number of incremental lines, while teeth with a sufficient nutritional
      support of their root showed a deviation of the histological age from the known
      actual age of 2-3 years only. For all patients, a detailed query concerning a
      variety of life-history parameters was established. We are able to show that
      especially previous pregnancies, skeletal traumata and renal diseases which all
      have a marked influence on the calcium metabolism result in hypomineralized
      incremental lines. The year of production of these hypomineralized lines could be
      dated precisely. Differential quality of incremental lines can, therefore, serve
      as a valuable tool in identification cases.

PMID- 11343859
TI  - Mole gun--an unusual firearm, a case note.
AB  - There are different kinds of types of firearms used worldwide and of different
      origin. This case note evaluates the mole gun, which cannot be found in the
      literature. This simple gun, which is usually used in the fields against moles,
      was used in an apartment as a trap against burglars. This instrument manufactured
      to be used as a trap against detrimental animals, and not to be used as a
      firearm, can create dangerous situations, if used for different purposes.

PMID- 11343860
TI  - Nutmeg (myristicin) poisoning--report on a fatal case and a series of cases
      recorded by a poison information centre.
AB  - In literature, cases of nutmeg abuse have been described repeatedly, but only one
      fatal case of poisoning was reported [1]. In the present case, myristicin (4
      microg/ml) was detected for the first time in the postmortal serum of a 55-year
      old woman. Identification was achieved with the aid of UV-VIS spectroscopy and
      TLC; for quantification, HPLC was used. Because also flunitrazepam (0.072
      microg/ml) was found, death had probably been due to the combined toxic effect of
      both substances. From 1996 to 1998, in a series of cases, seven poisonings with
      nutmeg were recorded by the Erfurt Poison Information Centre. Even where higher
      doses (20-80 g of powder) had been ingested, a life-threatening situation was
      never observed. In one of these cases, a myristicin blood level of 2 microg/ml
      was measured 8h after ingestion of two to three tablespoonful of nutmeg powder
      (approx. 14-21 g, or 280-420 mg/kg).

PMID- 11343861
TI  - Brazilian population database for the 13 STR loci of the AmpFlSTR Profiler Plus
      and Cofiler multiplex kits.
AB  - Allele frequencies for the 13 STR core loci (D3S1358, VWA, FGA, D8S1179, D21S11,
      D18S51, D5S818, D13S317, D7S820, CSF1PO, TPOX, THO1 and D16S539) included in the
      AmpFlSTR((R)) Profiler Plus and AmpFlSTR((R)) Cofiler kits were obtained for a
      sample of 700-800 genetically unrelated Brazilians. The expected performance of
      these loci for personal identification and paternity testing in the Brazilian
      population was estimated.

PMID- 11343863
TI  - Association analysis of polymorphism in the promoter region of the alpha2a
      adrenoceptor gene with schizophrenia and clozapine response.
AB  - There exists considerable evidence implicating the alpha (alpha) adrenergic
      system in the superior therapeutic effects of clozapine for the treatment of
      schizophrenia, as also its associated adverse hypersalivation side effect. It
      would seem plausible for variants of the adrenoceptors to be associated with the
      clozapine response. The present study tested the hypothesis that a biallelic
      polymorphism in the promoter region of the alpha2a-adrenoceptor gene confers
      susceptibility to schizophrenia, and is associated with a clozapine-induced
      (favorable) therapeutic response and/or a clozapine-induced hypersalivation.
      Ninety-seven treatment-resistant schizophrenic patients were assessed using the
      Brief Psychiatric Rating Scale before and after clozapine treatment. The results
      of clozapine treatment demonstrated that the alpha2a-adrenoceptor gene variants
      did not play a major role in the susceptibility, hypersalivation adverse effect
      or clozapine response of patients with schizophrenia. The polymorphism of the
      alpha2a-adrenoceptor gene investigated is not likely to play a major role in the
      pathogenesis of schizophrenic disorders or clozapine response, although the
      hypothesis that these genes are implicated in the cognitive deficit and
      polydipsia associated with schizophrenic disorders may, however, still warrant
      further study.

PMID- 11343864
TI  - Association between tryptophan hydroxylase gene polymorphism (A218C) and
      schizophrenic disorders.
AB  - The human tryptophan hydroxylase (TPH) gene, the rate-limiting enzyme in
      serotonin biosynthesis, was localized on human chromosome 11p14-p15.3. Variation
      within intron 7 of the TPH gene was found to influence serotonin metabolism in
      the brain. To explore the possible role of TPH in the pathogenesis of
      schizophrenic disorders, we genotyped the TPH A218C polymorphism in 196
      schizophrenic patients and 251 controls. The results demonstrated that genotype
      distribution was significantly different between schizophrenic patients and
      control subjects (P=0.002). No association was found between TPH genotypes and
      suicidal history in schizophrenic patients (P=0.239). The positive finding in
      this study suggests that the TPH 218A allele is a risk factor for schizophrenic
      disorders or is in linkage disequilibrium with the putative schizophrenia
      susceptibility locus in Han Chinese population.

PMID- 11343865
TI  - Association study of schizophrenia with polymorphisms at six candidate genes.
AB  - Clinical studies have shown that there is a genetic contribution to the
      pathogenesis of schizophrenia. The molecular mechanisms of effective
      antipsychotic drugs and recent advances in neural development suggest that
      several dopamine receptor, serotonin receptor and neurotrophic factor genes might
      be involved in the disorder. In this study, we assessed the associations between
      schizophrenia and polymorphisms in the D2 and D3 dopamine receptor (DRD2, DRD3),
      the serotonin 2A receptor (5HTR2A), the brain-derived neurotrophic factor (BDNF),
      the ciliary neurotrophic factor (CNTF) and the neurotrophin-3 (NT-3) genes. Our
      results suggest that the polymorphisms at the DRD3, 5HTR2A, CNTF and BDNF gene
      loci are unlikely to make our sample more genetically susceptible to
      schizophrenia. However, we found significant differences in microsatellite allele
      frequencies between schizophrenic and control groups for DRD2 in the whole sample
      and for DRD2 and NT-3 only in women. Therefore, clinical differences in the
      presentation of schizophrenia between gender might be related to genetic factors.

PMID- 11343866
TI  - Transmission disequilibrium analysis of HLA class II DRB1, DQA1, DQB1 and DPB1
      polymorphisms in schizophrenia using family trios from a Han Chinese population.
AB  - Our goal was to evaluate the role of HLA in the risk of developing schizophrenia,
      in a Han Chinese population. In several Japanese studies, there is evidence of
      association with DR1 and schizophrenia. A variety of other associations have been
      reported in other populations, including negative associations with DQbeta(*)0602
      and positive associations with DR1(*)0101. Using sequence specific
      oligonucleotides, we genotyped four HLA markers (DRB1, DQA1, DQB1 and DPB1) in
      165 family trios, consisting of Han Chinese schizophrenic subjects and their
      parents. Individual markers were analysed for transmission distortion in the
      trios using the transmission disequilibrium test. Multiple haplotype transmission
      was performed using the program TRANSMIT v2.5. The four markers were in strong
      linkage disequilibrium with each other (P value from 0.002 to 0). There was no
      evidence of overall transmission disequilibrium for each of the four loci. For
      DRB1, we did not find transmission distortion for the DRB1(*)04 and DRB1(*)08
      alleles, as reported previously, but the DRB1(*)03 allele was preferentially not
      transmitted (P=0.009), and the DRB1(*)13 allele was preferentially transmitted
      from parents to schizophrenic offspring (P=0.041). Using haplotypes of pairs of
      markers, a significant global P value of 0.019 was achieved when using DRB1 and
      DQA1, mainly as a result of the excess transmission of DRB1(*)13-DQA1(*)01
      (P=0.012) and a deficit in transmission of DRB1(*)03-DQA1(*)05 (P=0.002). In
      summary, we did not confirm any of the specific HLA allelic associations reported
      previously in Japanese or other populations. However, our results are compatible
      with the view that this region of HLA might contain a susceptibility gene which
      is in linkage disequilibrium with DRB1 and DQA1 genes.

PMID- 11343867
TI  - Vulnerability to involuntary movements over a lifetime trajectory of
      schizophrenia approaches 100%, in association with executive (frontal)
      dysfunction.
AB  - This study assessed the prevalence of involuntary movements among older
      inpatients with severe schizophrenia, many of whom had experienced a lifetime of
      illness and its treatment, and examined their neuropsychological correlates. The
      subjects of this study were 128 inpatients with a DSM-IV diagnosis of
      schizophrenia. They were assessed using the Abnormal Involuntary Movement Scale,
      the Mini-Mental State Examination for general cognitive impairment and the
      Executive Interview for executive dyscontrol; additionally, their medical records
      were reviewed in detail for treatment histories. Prevalence of involuntary
      movements was examined and their clinical correlates determined in relation to
      topography of movement disorder using logistic regression. In schizophrenia,
      prevalence of involuntary movements was: age <65years, 63%; 65-75years, 80%;
      >75years, 93%. The primary correlate both of overall and of orofacial movements
      was poor executive function, whereas the primary correlate of limb-trunkal
      movements was poor general cognitive function. On approaching the limits of human
      longevity following a lifetime trajectory of illness and its treatment,
      essentially 'all' patients with schizophrenia appear inherently vulnerable to the
      emergence of involuntary movements in topographically specific association with
      cognitive deficits.

PMID- 11343868
TI  - Synaptophysin and GAP-43 mRNA levels in the hippocampus of subjects with
      schizophrenia.
AB  - Synaptophysin and growth associated protein-43 (GAP-43) are synaptic proteins
      colocalized to the presynaptic terminal, and involved in regulating transmitter
      release and synaptic plasticity. Recent studies have proposed an alteration in
      the number of synapses in the brains of individuals with schizophrenia. As a
      corollary, we hypothesized that there may be an alteration in the level of mRNAs
      that code for synaptic proteins in brains of patients with schizophrenia. Using
      in situ hybridization, we investigated the levels of synaptophysin and GAP-43
      mRNA in the medial temporal lobe of 10 normal subjects, 11 subjects with
      schizophrenia and 10 psychiatric control subjects. Synaptophysin mRNA levels were
      significantly reduced in several hippocampal subfields in both the schizophrenic
      and psychiatric control groups. GAP-43 mRNA levels were not significantly reduced
      in either group. The implications of these findings are discussed in relation to
      neuroleptic treatment and the pathophysiology of mental illness.

PMID- 11343869
TI  - Increased frequency of activated lymphocytes in the cerebrospinal fluid of
      patients with acute schizophrenia.
AB  - We compared the cerebrospinal fluid (CSF) cytology of 30 acutely psychotic
      patients at the initial phase of their hospital treatment with that of 46 control
      individuals with no psychiatric disorder or central nervous system (CNS) disease.
      The cytological profile of May-Grunwald-Giemsa stained CSF cell slides of the
      patients was significantly different from that of the control population. The
      most striking finding was a significantly increased frequency of lymphoid cells
      showing morphological features of activation/stimulation and a decreased
      proportion of normal small lymphocytes. Many of the cells with aberrant
      morphology displayed structural details similar to those of the 'P cells'
      previously described in the blood of schizophrenic patients. The patients' CSF
      also contained elevated proportions of monocytes/macrophages, some of which were
      found in 'rosettes' with activated lymphocytes indicating an increased
      intercellular adhesion. Possible pathogenic mechanisms behind lymphocyte
      activation and macrophage dominance in the CSF of acutely ill psychotic patients
      are discussed.

PMID- 11343870
TI  - Corpus callosum and P300 in schizophrenia.
AB  - Functional abnormalities in the interhemispheric transfer via the corpus callosum
      in schizophrenia may result in filtering problems and information processing
      problems, which may in turn be related to the synchronization of cortical event
      related activity. To explore whether a relationship exists between corpus
      callosum (CC) size, measured with in-vivo magnetic resonance imaging, and late
      auditory event-related P300 potentials, 50 patients with schizophrenia as well as
      50 healthy controls were examined. The absolute CC size and subregional areas, as
      well as the CC areas adjusted for total brain volume, were not significantly
      different between patients with schizophrenia and controls. While no significant
      group differences were observed for P3a-, P3b-, PSW-amplitudes and P3b-latencies,
      P3a- and PSW-latencies were significantly prolonged for patients with
      schizophrenia. Absolute CC total size was significantly correlated with P3b
      amplitudes in healthy controls (r=0.29; P=0.044). In patients with schizophrenia,
      significant correlations were observed between the subregion of the posterior
      body of the CC and positive slow wave (PSW; r=0.47; P=0.001). P3a-, P3b- and PSW
      latencies were not significantly correlated to CC size in either patients with
      schizophrenia or healthy controls. The results are discussed in terms of the
      possibility that abnormalities in interhemispheric transfer may underlie the
      mechanisms of schizophrenia.

PMID- 11343862
TI  - A review of MRI findings in schizophrenia.
AB  - After more than 100 years of research, the neuropathology of schizophrenia
      remains unknown and this is despite the fact that both Kraepelin (1919/1971:
      Kraepelin, E., 1919/1971. Dementia praecox. Churchill Livingston Inc., New York)
      and Bleuler (1911/1950: Bleuler, E., 1911/1950. Dementia praecox or the group of
      schizophrenias. International Universities Press, New York), who first described
      'dementia praecox' and the 'schizophrenias', were convinced that schizophrenia
      would ultimately be linked to an organic brain disorder. Alzheimer (1897:
      Alzheimer, A., 1897. Beitrage zur pathologischen anatomie der hirnrinde und zur
      anatomischen grundlage einiger psychosen. Monatsschrift fur Psychiarie und
      Neurologie. 2, 82-120) was the first to investigate the neuropathology of
      schizophrenia, though he went on to study more tractable brain diseases. The
      results of subsequent neuropathological studies were disappointing because of
      conflicting findings. Research interest thus waned and did not flourish again
      until 1976, following the pivotal computer assisted tomography (CT) finding of
      lateral ventricular enlargement in schizophrenia by Johnstone and colleagues.
      Since that time significant progress has been made in brain imaging, particularly
      with the advent of magnetic resonance imaging (MRI), beginning with the first MRI
      study of schizophrenia by Smith and coworkers in 1984 (Smith, R.C., Calderon, M.,
      Ravichandran, G.K., et al. (1984). Nuclear magnetic resonance in schizophrenia: A
      preliminary study. Psychiatry Res. 12, 137-147). MR in vivo imaging of the brain
      now confirms brain abnormalities in schizophrenia. The 193 peer reviewed MRI
      studies reported in the current review span the period from 1988 to August, 2000.
      This 12 year period has witnessed a burgeoning of MRI studies and has led to more
      definitive findings of brain abnormalities in schizophrenia than any other time
      period in the history of schizophrenia research. Such progress in defining the
      neuropathology of schizophrenia is largely due to advances in in vivo MRI
      techniques. These advances have now led to the identification of a number of
      brain abnormalities in schizophrenia. Some of these abnormalities confirm earlier
      post-mortem findings, and most are small and subtle, rather than large, thus
      necessitating more advanced and accurate measurement tools. These findings
      include ventricular enlargement (80% of studies reviewed) and third ventricle
      enlargement (73% of studies reviewed). There is also preferential involvement of
      medial temporal lobe structures (74% of studies reviewed), which include the
      amygdala, hippocampus, and parahippocampal gyrus, and neocortical temporal lobe
      regions (superior temporal gyrus) (100% of studies reviewed). When gray and white
      matter of superior temporal gyrus was combined, 67% of studies reported
      abnormalities. There was also moderate evidence for frontal lobe abnormalities
      (59% of studies reviewed), particularly prefrontal gray matter and orbitofrontal
      regions. Similarly, there was moderate evidence for parietal lobe abnormalities
      (60% of studies reviewed), particularly of the inferior parietal lobule which
      includes both supramarginal and angular gyri. Additionally, there was strong to
      moderate evidence for subcortical abnormalities (i.e. cavum septi pellucidi-92%
      of studies reviewed, basal ganglia-68% of studies reviewed, corpus callosum-63%
      of studies reviewed, and thalamus-42% of studies reviewed), but more equivocal
      evidence for cerebellar abnormalities (31% of studies reviewed). The timing of
      such abnormalities has not yet been determined, although many are evident when a
      patient first becomes symptomatic. There is, however, also evidence that a subset
      of brain abnormalities may change over the course of the illness. The most
      parsimonious explanation is that some brain abnormalities are neurodevelopmental
      in origin but unfold later in development, thus setting the stage for the
      development of the symptoms of schizophrenia. Or there may be additional factors,
      such as stress or neurotoxicity, that occur during adolescence or early adulthood
      and are necessary for the development of schizophrenia, and may be associated
      with neurodegenerative changes. Importantly, as several different brain regions
      are involved in the neuropathology of schizophrenia, new models need to be
      developed and tested that explain neural circuitry abnormalities effecting brain
      regions not necessarily structurally proximal to each other but nonetheless
      functionally interrelated. (ABSTRACT TRUNCATED)

PMID- 11343871
TI  - P300 amplitude as a possible correlate of frontal degeneration in schizophrenia.
AB  - The existence of neurodegeneration is a debated issue in schizophrenia research.
      The P300 component of event-related electrical potentials (ERP) has been related
      to the different degree of damage to gray and white matter. This study explores
      the possible relationship between P300 amplitude and/or latency and the existence
      of degenerative processes in schizophrenia, by assessing its correlation with
      volume of sulcal CSF and duration of illness, as transversal indicators of
      neurodegeneration. Nineteen patients (14 males, 5 females) and 13 controls (6
      males, 7 females) were studied with MRI and electrophysiological records (P300).
      The possible influence of sex and age at the time of the exploration was
      statistically controlled in both groups. The results show a significant negative
      correlation between P300 amplitude and prefrontal CSF volume in the patient
      group. A lower though still significant correlation was also found between P300
      amplitude and duration of illness, whereas no correlation was found in the
      control group. These results support the hypothesis that P300 amplitude may be
      interpreted as a marker of neurodegeneration in schizophrenia.

PMID- 11343872
TI  - An association between reduced interhemispheric EEG coherence in the temporal
      lobe and genetic risk for schizophrenia.
AB  - Previous studies have suggested that schizophrenic patients show resting changes
      such as frequency-slowing and decreased coherence in the frontal and temporal
      area. We sought to determine whether these findings are also found in clinically
      unaffected siblings of schizophrenics and estimate heritability by calculating
      relative risk. We investigated two independent data sets: (1) from the NIMH St.
      Elisabeth's campus (59 schizophrenics, 76 unaffected siblings and 32 unrelated
      normal controls) and (2) from the NIH-campus (Bethesda) (59 schizophrenics, 90
      unaffected siblings and 26 unrelated normal controls). We computed power spectra
      and coherence on the first data set and then tried to replicate the results on
      the second data set. Power spectrum analysis suggested that schizophrenics are
      cortically hypoactivated, whereas in unaffected siblings, a tendency for
      hyperactivation was found. In contrast, spectral coherences (0.5-5Hz) were
      reduced in both data sets in the temporal lobe areas in schizophrenics and in
      their unaffected siblings. Changes were most pronounced for the interhemispheric
      coherence linking both posterior temporal lobe areas. Relative risk calculations
      (lambda(S)) ranged between 3.7 and 9.8, depending on phenotype definition. Thus,
      while power spectrum EEG abnormalities may be state-dependent, reduced coherence
      as a possible measure of neuronal synchronization is familial and potentially a
      heritable trait related to genetic risk for schizophrenia.

PMID- 11343873
TI  - EEG-correlates of facial affect recognition and categorisation of blurred faces
      in schizophrenic patients and healthy volunteers.
AB  - The ability to recognise emotional expressions of faces and the ability to
      categorise blurred and non-blurred faces and complex objects was tested in 16
      schizophrenic in-patients and 16 healthy volunteers. EEGs were recorded during
      performance of the tasks and event-related potentials were compared between
      groups. Patients performed worse than healthy volunteers in recognition of facial
      affect but not in categorisation of blurred faces. Furthermore, within a 180
      250ms latency range patients showed reduced amplitudes during affect recognition
      compared with controls but not during categorisation of blurred faces. Amplitudes
      recorded at frontal electrode sites were associated with performance in facial
      affect recognition. These results provide a first clue to the neurophysiological
      basis of the widely reported facial affect recognition deficit in schizophrenic
      patients.

PMID- 11343874
TI  - Conditioned blocking and schizophrenia: a replication and study of the role of
      symptoms, age, onset-age of psychosis and illness-duration.
AB  - Measures of selective attention processing like latent inhibition (LI) and
      conditioned blocking (CB) are disturbed in some patients with schizophrenia. [LI
      is the delay in learning about the associations of a stimulus that has been
      associated with no event (versus de novo learning); CB is the delay in learning
      the associations of a stimulus-component when the other component has already
      started to acquire these associations.] We proposed: (1) to replicate the
      reported decreases of CB in patients without paranoid-hallucinatory symptoms; (2)
      to see if CB depends on the age of illness-onset and its duration, as reported
      for LI. We studied 101 young and old, acute and chronically ill patients with
      schizophrenia, of whom 62 learned a modified 'mouse-in-house' CB task, and
      compared them with 62 healthy controls matched for age, education and socio
      economic background. CB was more evident in patients with a diagnosis of paranoid
      schizophrenia than other subtypes. An unusual persistence of high CB scores
      through testing was associated with productive symptoms (including positive
      thought disorder). Reduced CB related to the expression of (a) Schneider's first
      rank symptoms of ideas-of-reference and (b) to negative symptoms like poor
      rapport and poor attention. CB was less evident in the older patients and those
      with an earlier illness-onset. In contrast to the similar LI test of selective
      attention, CB is found in patients with paranoid schizophrenia and its expression
      is not related closely to illness duration. This implies that the two tests
      reflect the activity of different underlying processes. We suggest that reduced
      CB on initial test-trials in nonparanoid schizophrenia reflects the unusual
      persistence of controlled information processing strategies that would normally
      become automatic during conditioning. In contrast, continued CB during testing
      reflects an unusual persistence of automatic processing strategies.

PMID- 11343875
TI  - Impact of prepulse characteristics on the detection of sensorimotor gating
      deficits in schizophrenia.
AB  - Schizophrenia patients have prominent deficits in information processing that can
      be detected by measures of prepulse inhibition (PPI) of the startle response.
      Deficient PPI in schizophrenia is thought to reflect a failure of brain-based
      information 'protective' mechanisms that normally inhibit responsivity for 30
      500ms after a weak prepulse stimulus. The relationship between specific prepulse
      stimulus characteristics and PPI deficits in this study was examined in 31
      schizophrenia patients and 34 normal comparison subjects. Schizophrenia patients
      had overall deficits in PPI across four conditions where the prepulse was either
      discrete (abrupt) or continuous (sustained) and consisted of either white noise
      or a pure tone. On inspection and analysis of the data, it appears that the white
      noise conditions, rather than tone conditions, account for the group differences.
      Thus, the discrete white noise prepulse was most effective in eliciting PPI
      deficits, resulting in a large effect size between groups (d=0.85; P<0.01).
      Deficits in information-protective mechanisms in schizophrenia may be
      differentially sensitive to specific stimulus characteristics; this observation
      may be relevant both to the neurobiology of information processing deficits in
      schizophrenia and to the methodologies for studying these deficits
      experimentally.

PMID- 11343876
TI  - Auditory feature conjunction in patients with schizophrenia.
AB  - The neural mechanisms supporting performance during single feature and feature
      conjunction tasks were investigated in patients with schizophrenia and age
      matched controls using event-related brain potentials. In different blocks of
      trials, participants responded to auditory targets defined by one of two pitches,
      one of two locations, or both pitch and location. All participants were faster
      and more accurate in detecting targets defined by a single feature than for
      targets defined by a conjunction of features. Compared with the single feature
      conditions, conjunction targets were associated with enhanced negativity between
      200 and 250ms (N2) post-stimulus and showed a delayed P3b latency. Compared with
      controls, patients with schizophrenia showed reduced N1 and N2 amplitude elicited
      by single and conjunctive targets. The results are consistent with defective
      perceptual mechanisms in schizophrenia. The fact that both performance and P3b
      amplitude were similar in patients and controls suggests that controlled
      processes compensate for processes normally carried out by early perceptual
      mechanisms.

PMID- 11343877
TI  - The muscarinic receptor agonist BuTAC, a novel potential antipsychotic, does not
      impair learning and memory in mouse passive avoidance.
AB  - (5R,6R)-6-(3-butylthio-1,2,5-thiadiazol-4-yl)-1-azabicyclo[3.2.1]octane) (BuTAC)
      is a novel, selective muscarinic receptor ligand with partial agonist mode of
      action at muscarinic M2 and M4 and antagonist mode of action at M1, M3 and M5
      receptor subtypes in cloned cell lines. BuTAC exhibits functional dopamine
      receptor antagonism despite its lack of affinity for dopamine receptors, and
      parasympathomimetic effects in mice are produced only at doses well beyond the
      doses exhibiting the antipsychotic-like effects. In the present study we
      investigated the effects of BuTAC and the antipsychotic compounds clozapine,
      sertindole and olanzapine using one trial passive avoidance with mice as a model
      of learning and memory. Pharmacologically relevant doses of BuTAC and reference
      antipsychotics were identified, based on inhibition of apomorphine-induced
      climbing in mice as an assay measuring antidopaminergic potency. When ratios
      between the minimum effective dose (MED) for impairment of retention in passive
      avoidance and the MED for inhibition of apomorphine-induced climbing were
      calculated, BuTAC displayed a high ratio of >10, compared with clozapine (0.3),
      sertindole (3) and olanzapine (3). These data suggest that BuTAC is a potential
      novel antipsychotic which may have favourable effects on aspects of learning and
      memory.

PMID- 11343878
TI  - Association and excess of transmission of a DRD2 haplotype in a sample of French
      schizophrenic patients.
AB  - The gene which codes for dopamine receptor D2 (DRD2) is considered as one of the
      most relevant candidate genes in schizophrenia. Previous genetic studies focusing
      on this gene gave conflicting results, potentially because of the differences in
      methodology (linkage versus association studies), and the different loci analyzed
      (the DRD2 gene having many polymorphisms). We used a progressive strategy with
      three different approaches (case/control, haplotype relative risk and
      transmission disequilibrium test) and investigated two genetic polymorphisms
      (TaqI B1/B2 and TaqI A1/A2, spanning the coding region of the DRD2 gene) in 50
      patients with DSM-IV diagnoses of schizophrenia, in their 100 parents and in 50
      healthy, matched controls. Firstly, we found a significant excess of the two
      alleles (B2 and A2) in the schizophrenic group compared to unaffected controls.
      Secondly, we found an excess of transmission from the parents to their affected
      children, using the haplotype relative risk design applied to the B2A2 haplotype.
      Finally, the transmission disequilibrium test showed evidence for linkage between
      B2A2 haplotype and schizophrenia. The significant excess of the B2A2 haplotype in
      schizophrenic patients is specifically observed in a subsample of patients with a
      disease onset occurring after 20 years of age. As the haplotype contains nearly
      the entire DRD2 gene, we found convergent evidence in our sample for a
      significant role of the DRD2 gene in the risk for schizophrenia. This haplotype
      may be more specifically involved in the disorder's onset at a later age in some
      patients, or, alternatively, may be implicated as a modifying factor acting on
      age of onset.

PMID- 11343879
TI  - Impaired suppression of processing in schizophrenic patients suggested by ERPs
      obtained in a selective attention task.
AB  - In the present study, we focused on the ability of suppression of processing in
      schizophrenic patients, using event-related potentials (ERPs) recorded during a
      selective attention task. During the task, subjects were required to focus on one
      ear, counting deviant stimuli, those deviating in duration from a sequence of
      standard stimuli. We compared amplitude data of two positive components differing
      in latency elicited by standard stimuli, which reflect suppression of stimulus
      processing, between schizophrenic patients and normal controls. Significant
      between-group differences were obtained specifically in the right ear attended
      condition, suggesting impaired suppression of processing in schizophrenics
      mediated in the left hemisphere.

PMID- 11343880
TI  - Morphological characterization of microspheres, films and implants prepared from
      poly(lactide-co-glycolide) and ABA triblock copolymers: is the erosion controlled
      by degradation, swelling or diffusion?
AB  - Erosion of biodegradable parenteral delivery systems (PDS) based on ABA
      copolymers consisting of poly(L-lactide-co-glycolide) (PLGA) A-blocks attached to
      polyethylene oxide (PEO) B-blocks, or PLGA is important for the release of
      macromolecular drugs. The degradation behavior of four types of PDS, namely
      extruded rods, tablets, films and microspheres, was studied with respect to
      molecular weight, mass, polymer composition and shape and microstructure of the
      PDS. For each device the onset time of bulk erosion (t(on)) and the apparent rate
      of mass loss (k(app)) were calculated. In the case of PLGA, the t(on) was 16.2
      days for microspheres, 19.2 days for films and 30.1 days for cylindrical implants
      and tablets. The k(app) was 0.04 days(-1) for microspheres, 0.09 days(-1) for
      films, 0.11 days(-1) for implants and 0.10 days(-1) for tablets. The degradation
      rates were in the same range irrespective of the geometry and the micrographs of
      eroding PDS demonstrated pore formation; therefore, a complex pore diffusion
      mechanism seems to control the erosion of PLGA devices. In contrast, PDS based on
      ABA copolymers showed swelling, followed by a parallel process of molecular
      weight degradation and polymer erosion, independent of the geometry. The contact
      angles of ABA films increased either with decreasing PEO content or with
      increasing chain length of the PEO B-blocks. In summary, the insertion of a
      hydrophilic B-block leads to an erosion controlled by degradation of ABA
      copolymers, whereas for PLGA a complex pore diffusion of degradation products
      controls the rate of bulk erosion.

PMID- 11343881
TI  - A new 5-aminosalicylic acid multi-unit dosage form for the therapy of ulcerative
      colitis.
AB  - The aim of the present study was to develop a multi-unit dosage form containing 5
      aminosalicylic acid (5-ASA) for the treatment of ulcerative colitis (UC),
      optimised on the basis of recent studies indicating that UC patients have higher
      intestinal pH than was previously thought to be the case. Pellets with a drug
      content of 77.4% were prepared by a granulation and spheronization process and
      then coated with a new pH sensitive poly(meth)acrylate copolymer (Eudragit((R))
      FS 30D) to achieve site specific drug release close to the ileocecal valve.
      Dissolution tests were carried out in a paddle dissolution apparatus in media
      simulating pH conditions at various locations in the gastrointestinal tract. The
      pellets released rapidly at pH values above 7.5. Between 6.8 and 7.2 drug release
      was found to be zero order, while at pH 6.5 and below no release occurred. In a
      biorelevant medium which simulates the fasting proximal small intestine fluid it
      was shown that neither surfactants (sodium taurocholate and lecithin) nor changes
      in ionic strength trigger drug release. Compared to 5-ASA pellets coated with the
      well established Eudragit((R)) S, and to currently marketed products licensed for
      the treatment of UC, the multi-unit dosage form coated with the new polymer
      exhibited an in vitro dissolution profile more appropriate to the pH profile of
      the ileum and the colon observed in UC patients.

PMID- 11343882
TI  - Enzymatic degradation of cross-linked high amylose starch tablets and its effect
      on in vitro release of sodium diclofenac.
AB  - The influence of several physicochemical parameters on enzymatic hydrolysis and
      the in vitro release of sodium diclofenac (SDic) from cross-linked high amylose
      starch (Contramid) (CLA) tablets was evaluated. These parameters included pH,
      ionic strength of the medium, enzyme concentration, compression force and
      incorporation of gel-forming polymers such as hydroxypropyl methylcellulose
      (HPMC), poly(ethylene oxide) (PEO) and poly(vinyl alcohol) into the tablet. Pure
      CLA tablets were incubated in phosphate buffer (pH 6.8) containing alpha-amylase
      and the extent of enzymatic erosion was determined by gravimetry. Release of SDic
      from CLA tablets, in the presence of alpha-amylase, was measured using a USP type
      III dissolution apparatus. For low alpha-amylase concentrations (<2250 IU/l), the
      drug release was mainly diffusion-controlled. At higher alpha-amylase
      concentrations (>4500 IU/l) both diffusion and erosion contributed to the release
      of SDic. The hydrolysis kinetics of CLA tablets by alpha-amylase was biphasic.
      During the first phase (2-4 h), the hydrolysis rate was hyperbolically related to
      the alpha-amylase concentration but was practically alpha-amylase concentration
      independent during the second phase. Enzymatic erosion and drug release kinetics
      appear to be relatively independent of ionic strength, pre-incubation time in
      simulated gastric fluid, and compression force of the tablets (6-34 kN).
      Incorporation of HPMC or PEO into the tablet resulted in a significant decrease
      of both tablet erosion and drug release rates.

PMID- 11343883
TI  - Preparation and in vivo evaluation of mucoadhesive microparticles containing
      amoxycillin-resin complexes for drug delivery to the gastric mucosa.
AB  - In this work, microparticles consisting of amoxycillin-loaded ion-exchange resin
      encapsulated in mucoadhesive polymers (polycarbophil and Carbopol 934) were
      prepared with the aim of increasing the efficacy of amoxycillin in the treatment
      of peptic ulcers by achieving targeted delivery to the gastric mucosa and
      prolonged drug release. An oil-in-oil solvent evaporation technique was
      conveniently modified in order to obtain polymer microparticles containing
      multiple amoxycillin-resin cores. Polycarbophil microparticles were spherical,
      Carbopol 934 microparticles irregular. In vitro release of amoxycillin was rapid
      with or without a polymer coating. Gastrointestinal transit in rats was
      investigated by fluorescence microscopy using particles loaded with fluorescein
      instead of amoxycillin: gastric residence time was longer, and the distribution
      of the particles on the mucosa apparently better, without any polymer coating.

PMID- 11343884
TI  - The examination of skin lipid model systems stressed by ultraviolet irradiation
      in the presence of transition metal ions.
AB  - In this study, we investigated the effects of ultraviolet (UV) radiation on lipid
      peroxidation in the presence of ionised iron as a transition metal. Fatty acids
      as important intercellular stratum corneum lipids and liposomes were used to
      model skin lipid systems for our experiments. A UV-A laser and a broad spectrum
      UV lamp were used to create high-level radiation. UV-related damage was
      quantified by the thiobarbituric acid assay detecting malondialdehyde.
      Electrospray mass spectrometry was used to characterise peroxidation products
      following UV exposure. We have shown that hydro- and endoperoxides are long
      stable intermediates deriving from lipid peroxidation. The incorporation of
      unsaturated fatty acids into phospholipid liposomes increased the average
      liposomal diameter and enhanced sensitivity to UV radiation. By comparing our
      data from laser induced monochromatic UV-A radiation and broad-spectrum UV
      irradiation, we have demonstrated that UV-A radiation can also induce lipid
      peroxidation in lipid model systems.

PMID- 11343885
TI  - Sustained-release effect of codried excipients of microcrystalline cellulose and
      Ganoderma fiber.
AB  - The sustained-release effects of codried excipient of modified Ganoderma (treated
      with alkaline solution) and microcrystalline cellulose at different ratios were
      examined using acetaminophen (ACT) as a model drug. Results demonstrate that the
      crushing strength of most ACT tablets made with codried powder at all ratios
      increased as compaction force increased; but a rapid decline was observed when
      compression force exceeded 2 tons. Drug release from tablets compressed at 0.5
      ton increased as modified Ganoderma fiber content increased. But when the
      compression force exceeded 1 ton, the release rate was not influenced by the
      compaction force or the increasing content of Ganoderma fiber. However, the
      dissolution of ACT from these tablets could be sustained for longer than 24 h.
      The extent of drug release was shown to increase with increasing amounts of
      modified Ganoderma in the codried excipient. The addition of disintegrants could
      further accelerate the drug release from the tablet. Drug release was also
      dependent upon the amount and kind of disintegrant used. The influence was in the
      following order: primojel>crospovidone>starch 1500.

PMID- 11343886
TI  - Comparison of impact of the different hydrophilic carriers on the properties of
      piperazine-containing drug.
AB  - The objective of this study was to determine the impact of a series of nonionic
      surfactants on the solubility of piperazine-containing drug (meclizine, MZ) in
      comparison to that of natural cyclodextrins (alpha-CD and beta-CD) and dimethyl
      beta-cyclodextrin (DM-beta-CD). The solubility of the drug was studied in either
      CDs solutions or nonionic surfactant solutions. Three classes of nonionic
      surfactants were used namely; polyoxyethylene (POE) sorbitan fatty acid esters
      (polysorbates), POE fatty acid esters (Myrjs) and polyethylene oxide (PEO) fatty
      alcohol ethers (Brijs and Eumulgins). The solubility of MZ was increased linearly
      with the increasing surfactant concentration, indicating that micellar
      solubilization follows the partition model. It was found that the longer the
      hydrocarbon chain in a homologous series, the more efficient is the solubilizing
      power of surfactant. For example, polysorbate 80 (Tween-80) is a more efficient
      solubilizer than polysorbate 20 (Tween-20), indicating that the drug was
      incorporated in the core of micelle more than the capsular region of the micelle.
      On the other hand, in case of POE fatty acid esters, the solubilizing power
      increased with decreasing polyoxyethylene chain as Myrj 53 was more efficient
      than Myrj 59. In class of PEO fatty alcohol ethers, the shorter the hydrophilic
      chain and longer lipophilic chain, the more efficient was the solubilizing
      capacity. Thus, Brij 58 was more efficient solubilizer than Brij 35 and Eumulgin
      C1000 was more active than Eumulgin C1500. Comparatively, Eumulgin C1000 had the
      highest solubilizing power for MZ among the studied PEO fatty alcohol ethers and
      other groups of surfactants. The solubility action of surfactants toward MZ was
      increased by raising the temperature of the surfactant solutions from 30 to 45
      degrees C. Hydrophilic macromolecules (PEG 1000 and PEG 6000) or cosolvents
      (glycerol and propylene glycol) have a very slight effect on the solubility of MZ
      and confirm the predominance of hydrophobic interaction between the drug and
      nonionic surfactants. A(L)-type phase solubility diagrams were obtained for the
      drug with alpha-, beta- and DM-beta-CDs showing that the solubility of MZ was
      enhanced through inclusion complexation. Comparatively, DM-beta-CD had the
      highest solubilizing efficiency for the drug among the investigated CDs, which
      could be attributed to its larger hydrophobic cavity size.

PMID- 11343887
TI  - Influence of the centrifugal granulating process on the properties of layered
      pellets.
AB  - Drug-layered pellets based on microcrystalline cellulose (MCC) beads as
      substrates were prepared using a laboratory-scale centrifugal granulator. The
      effect of three independent process parameters (rotor rotation speed, slit air
      flow rate, and spray air rate) on responses describing the amount of drug loss
      during the process, amount of agglomerates, bulk density, flowability,
      friability, shape, and surface roughness were studied using a 3(3) full factorial
      experimental design. The variables studied were found to have a significant
      influence on the responses evaluated. Rotor rotation speed and slit air flow rate
      had a significant positive influence on the amount of drug loss during the
      process and the amount of agglomerates, whereas rotor rotation speed and spray
      air rate had the same effect on the bulk density, flowability, and the roundness
      of the pellets. The amount of agglomerates and the roundness value of the pellets
      were negatively affected by the spray air rate while the slit air flow rate
      showed the same effect on the bulk density and flow rate of the pellets. In
      addition to the main effects, there were some significant paired interactions
      between slit air flow rate and spray air rate as well as rotor rotation speed and
      slit air flow rate. Based on the results, the significance of these three
      parameters should be considered carefully for quality pellet preparation by the
      centrifugal granulating technique using MCC beads as substrates.

PMID- 11343888
TI  - Drug diffusion mechanism through pH-sensitive hydrophobic/polyelectrolyte
      hydrogel membranes.
AB  - Methylmethacrylate/dimethylaminoethyl methacrylate cross-linked with
      divinylbenzene is a pH-sensitive hydrogel. We have studied the diffusion
      mechanisms of drugs with different water solubilities through this hydrogel. A
      water-soluble model drug (aminopyrine) was used to study the diffusion
      coefficient changes in different pHs. The results showed a water-content
      dependent diffusion for this pH-sensitive polycationic hydrogel. However,
      decreasing the solubility of the drug and increasing the hydrophobic character of
      the polymer by changing the pH caused a greater affinity (or partition
      coefficient) between the hydrogel and the drug. Aminopyrine diffusion was shown
      to follow the free-volume theory, suggesting the 'pore' type mechanism for water
      soluble drugs, while the 'partition' or 'solution-diffusion' mechanism better
      described the slow diffusion of water insoluble solutes through this pH-sensitive
      hydrogel. Comparing the swelling interface number for aminopyrine release through
      this pH-sensitive hydrogel showed a non-Fickian mechanism in the hydrated form of
      the hydrogel (pH 1.2), while Fickian in the dehydrated form (pH 7.4).

PMID- 11343889
TI  - Controlled-release tablets from carrageenans: effect of formulation, storage and
      dissolution factors.
AB  - The purpose of this study was to investigate the potential of two carrageenans,
      iota-carrageenan and lambda-carrageenan for the preparation of controlled-release
      tablets. Tablets were compressed on a Carver press and the effect of formulation
      factors, moisture, and storage on the release of theophylline was studied. The
      effect of sodium chloride in the tablet formulation and a change in the ionic
      strength of the dissolution media was studied on the release of three model
      drugs. The release rate increased both with an increase in tablet diameter and
      increase in drug to carrageenan ratio in the tablets. The two lubricants studied
      had a negligible effect on the rate of drug release at their commonly used
      concentrations. Moisture content of carrageenans, storage of tablets at 37
      degrees C/75% RH for 3 months, and incorporation of 10% sodium chloride in the
      tablets did not have any significant effect on the release rate. The change in
      ionic strength of simulated gastric fluid altered the release rate whereas the
      ionic strength of simulated intestinal fluid did not have a significant effect on
      the release rate. Carrageenan tablets were relatively insensitive to small
      changes in formulation parameters and dissolution conditions.

PMID- 11343890
TI  - About the use of stoichiometric hydroxyapatite in compression - incidence of
      manufacturing process on compressibility.
AB  - Literature concerning calcium phosphates in pharmacy exhibits the chemical
      diversity of the compounds available. Some excipient manufacturers offer
      hydroxyapatite as a direct compression excipient, but the chemical analysis of
      this compound usually shows a variability of the composition: the so-called
      materials can be hydroxyapatite or other calcium phosphates, uncalcined (i.e.
      with a low crystallinity) or calcined and well-crystallized hydroxyapatite. This
      study points out the incidence of the crystallinity of one compound (i.e.
      hydroxyapatite) on the mechanical properties. Stoichiometric hydroxyapatite is
      synthesized and compounds differing in their crystallinity, manufacturing process
      and particle size are manufactured. X-Ray diffraction analysis is used to
      investigate the chemical nature of the compounds. The mechanical study (study of
      the compression, diametral compressive strength, Heckel plots) highlights the
      negative effect of calcination on the mechanical properties. Porosity and
      specific surface area measurements show the effect of calcination on compaction.
      Uncalcined materials show bulk and mechanical properties in accordance with their
      use as direct compression excipients.

PMID- 11343891
TI  - Effects of processing conditions on the rheological behavior of collagen
      dispersions.
AB  - Biomedical collagen preparations are mainly based on liquid aqueous preparations
      either used directly as injectables or transferred for example into solid
      implants or porous devices. In all cases the viscosity of the dispersion or
      solution has to be controlled or adjusted by pH, temperature, collagen
      concentration or crosslinking. We tested these effects on the rheological and
      structural properties of collagen fiber dispersions focusing on oscillatory
      rheometry. With increasing difference between pH and pI viscosity increased and
      went through a maximum with less rigidity of the fibers. The dispersions acted
      like a predominantly permanently linked network. This character changed to only
      partially linked at low collagen concentration due to isolation of the individual
      fibers. Up to 40 degrees C, temperature is a tool suitable for adjusting
      viscosity without changes in the network structure. At 50 degrees C, fourier
      transform - infrared spectroscopy (FT-IR) spectroscopy indicated the transition
      of the helical into random coil structure. Renaturation of the helices was found
      upon cooling but atomic force microscopy (AFM) indicated severe temperature
      induced damages of the fibers. Crosslinking with glutaraldehyde (GTA) leads to an
      increase in viscosity and the effect on the network structure depends on the
      processing conditions.

PMID- 11343892
TI  - Colorimetric determination of tocopheryl acetate (vitamin E) in pure form and in
      multi-vitamin capsules.
AB  - A simple, accurate and sensitive method for the determination of micro amounts of
      vitamin E (V(E)) in pure form and in multi-vitamin capsules is described. The
      method is based on the reduction of tetrazolium blue in slightly alkaline medium
      by vitamin E after extraction from aqueous EDTA medium with petroleum ether and
      transesterification. The oxidation reduction reaction occurs after 10 min of
      heating in a water bath at 90+/-2 degrees C, leading to the formation of a highly
      coloured formazan derivative. Different variables affecting the colour
      development were investigated and optimized. Absorbance measurements were made at
      526 nm and the calibration graph was linear for 0.2-11.0 microg/ml of (V(E)) with
      relative precision of about 0.7-1.5% when the standard additions method is used.

PMID- 11343894
TI  - Nucleus and gene expression: Web alert.
AB  - A selection of World Wide Web sites relevant to papers published in this issue of
      Current Opinion in Cell Biology.

PMID- 11343896
TI  - Histone methylation versus histone acetylation: new insights into epigenetic
      regulation.
AB  - Post-translational addition of methyl groups to the amino-terminal tails of
      histone proteins was discovered more than three decades ago. Only now, however,
      is the biological significance of lysine and arginine methylation of histone
      tails being elucidated. Recent findings indicate that methylation of certain core
      histones is catalyzed by a family of conserved proteins known as the histone
      methyltransferases (HMTs). New evidence suggests that site-specific methylation,
      catalyzed by HMTs, is associated with various biological processes ranging from
      transcriptional regulation to epigenetic silencing via heterochromatin assembly.
      Taken together, these new findings suggest that histone methylation may provide a
      stable genomic imprint that may serve to regulate gene expression as well as
      other epigenetic phenomena.

PMID- 11343897
TI  - Mediator complexes and transcription.
AB  - Over the past decade, various components of the transcription machinery have been
      identified as potential targets for activators. Recently, metazoan versions of
      yeast Mediator have been isolated and found to act as key coactivators to many
      transcription factors. Recent work has defined the composition, function and
      biology of metazoan mediator complexes, which has led us to propose a new
      nomenclature for the variously named versions of the mediator complex.

PMID- 11343898
TI  - Turning telomeres off and on.
AB  - We envision multiple steps in telomere maintenance, based largely on genetic data
      from budding yeast. First, the telomere must unfold or open itself such that the
      free end is accessible to the appropriate enzymatic machinery. Second, telomerase
      must be recruited, together with the DNA replication machinery that synthesizes
      the C-rich strand. The processivity of telomerase is regulated both by a length
      sensing feedback mechanism and by second-strand synthesis. Finally, the telosome
      refolds into a protective end structure. If telomerase is nonfunctional,
      recombination may occur once telomeres are open. Multiple pathways regulate these
      different steps, producing a highly dynamic chromosomal cap.

PMID- 11343899
TI  - Spliceosomal UsnRNP biogenesis, structure and function.
AB  - Significant advances have been made in elucidating the biogenesis pathway and
      three-dimensional structure of the UsnRNPs, the building blocks of the
      spliceosome. U2 and U4/U6*U5 tri-snRNPs functionally associate with the pre-mRNA
      at an earlier stage of spliceosome assembly than previously thought, and
      additional evidence supporting UsnRNA-mediated catalysis of pre-mRNA splicing has
      been presented.

PMID- 11343900
TI  - Pre-mRNA splicing in the new millennium.
AB  - The past year has witnessed refinements in models of spliceosome assembly
      pathways and in the understanding of how splicing factors of the serine/arginine
      rich (SR) protein family function. The role of splicing in human genetic diseases
      has also received a lot of attention recently as exonic splicing enhancers become
      better understood.

PMID- 11343902
TI  - mRNA turnover.
AB  - Nuclear RNA-binding proteins can record pre-mRNA processing events in the
      structure of messenger ribonucleoprotein particles (mRNPs). During initial rounds
      of translation, the mature mRNP structure is established and is monitored by mRNA
      surveillance systems. Competition for the cap structure links translation and
      subsequent mRNA degradation, which may also involve multiple deadenylases.

PMID- 11343901
TI  - Nucleocytoplasmic transport enters the atomic age.
AB  - Nucleocytoplasmic transport occurs through nuclear pore complexes (NPCs) and is
      mediated by saturable transport receptors that shuttle between the nucleus and
      cytoplasm. Our understanding of the molecular interactions underlying this
      process has improved dramatically as a result of the elucidation of the crystal
      structures of several nuclear transport factors either alone or in a complex with
      other components of the nuclear transport machinery. Furthermore, a conserved
      family of proteins, which is distinct from the well characterized family of
      importin beta-like nuclear export receptors, is implicated in the export of
      messenger RNA to the cytoplasm.

PMID- 11343903
TI  - Diversity in translational regulation.
AB  - Translational control of individual mRNAs relies on cis-regulatory elements,
      which are often found in the 3' untranslated region. The best characterized of
      these regulate cytoplasmic polyadenylation, and much of this process can now be
      defined in terms of molecular interactions, protein modifications and their
      consequences. Biochemical and genetic approaches have advanced the understanding
      of the many instances of translational regulation that are crucial for body
      patterning in Drosophila. For example, in vitro translation systems have been
      used to study the regulatory mechanisms, and genetic interactions have been
      instrumental in establishing a link between a regulatory factor and a component
      of the translational apparatus. Although most examples of control are thought to
      affect the initiation of translation, two classes of regulatory factors, one a
      protein and one a short non-coding RNA now appear to inhibit protein synthesis
      during elongation. Diversity seems to be a central feature of translational
      control, both in the mechanisms themselves and in the situations where this form
      of regulation is used.

PMID- 11343904
TI  - Regulation and function of the p53 tumor suppressor protein.
AB  - Loss of the p53 tumor suppressor pathway contributes to the development of most
      human cancers. p53 is a nuclear protein that functions as a regulator of
      transcription. Significant advances have been made recently in our understanding
      of how p53 function is regulated and the mechanisms by which p53 mediates its
      effects.

PMID- 11343905
TI  - Chromosome stability, DNA recombination and the BRCA2 tumour suppressor.
AB  - The BRCA2 tumour suppressor works in DNA recombination and repair pathways to
      preserve genome integrity. Recent progress provides fresh insights into its role
      as a regulator of the Rad51 recombination protein, underpinning a model in which
      BRCA2's involvement in chromosome stability and tumour suppression arises from
      its participation in recombinational processes essential for DNA replication.

PMID- 11343906
TI  - Membrane-bound transcription factors: regulated release by RIP or RUP.
AB  - Regulated nuclear transport of transcription factors from cytoplasmic pools is a
      major route by which eukaryotes control gene expression. Exquisite examples are
      transcription factors that are kept in a dormant state in the cytosol by membrane
      anchors; such proteins are released from membranes by proteolytic cleavage, which
      enables these transcription factors to enter the nucleus. Cleavage can be
      mediated either by regulated intramembrane proteolysis (RIP) catalysed by
      specific membrane-bound proteases or by regulated ubiquitin/proteasome-dependent
      processing (RUP). In both cases processing can be controlled by cues that
      originate at or in the vicinity of the membrane.

PMID- 11343907
TI  - Intracellular signaling from the endoplasmic reticulum to the nucleus: the
      unfolded protein response in yeast and mammals.
AB  - Cellular survival of endoplasmic reticulum stress requires the unfolded protein
      response (UPR), a stress response first elucidated genetically in yeast. While we
      continue to refine our knowledge of the yeast system, especially the breadth and
      significance of the transcriptional response, conservation of the system's
      elements has allowed identification of corresponding and additional components of
      the mammalian UPR. Recent results reveal that the output of the mammalian UPR
      reaches beyond transcriptional regulation of secretory pathway components to
      control of general translation, the cell cycle and programmed cell death.

PMID- 11343908
TI  - Circadian regulation of gene expression in animals.
AB  - Circadian timekeepers reside in most body cells of Drosophila and mammals. The
      discovery of new clock genes suggests that circadian oscillations are generated
      by interconnected feedback loops employing transcriptional and post-translational
      mechanisms. In mammals, a master pacemaker localized in the suprachiasmatic
      nucleus synchronizes peripheral clocks via humoral cues. However, restricted
      feeding can uncouple peripheral oscillators from the suprachiasmatic pacemaker.

PMID- 11343909
TI  - Nuclear pores and nuclear assembly.
AB  - Communication between the nucleus and cytoplasm occurs through large
      macromolecular structures, the nuclear pores. Quantitative scanning transmission
      electron microscopy has estimated the mass of a nuclear pore to be 60 million
      Daltons in yeast and 120 million Daltons in vertebrates. The past two years were
      noteworthy in that they saw: 1) the purification of both the yeast and vertebrate
      nuclear pores, 2) the initial description of routes through the pore for specific
      transport receptors, 3) glimpses of intranuclear organization imposed by the
      nuclear pores and envelope and 4) the revelation of new and pivotal roles for the
      small GTPase Ran not only in nuclear import but in spindle assembly and nuclear
      membrane fusion.

PMID- 11343910
TI  - Kinase chips hit the proteomics era.
AB  - Protein kinase chips, in which kinases are tested for their ability to
      phosphorylate immobilized substrates, have been developed and used to evaluate
      the protein kinases encoded by the yeast genome. This new technology promises to
      be a valuable addition to the biochemists' and cell biologists' arsenal for
      evaluating the substrate selectivity and function of protein kinases in cell
      signaling.

PMID- 11343911
TI  - The WWE domain: a common interaction module in protein ubiquitination and ADP
      ribosylation.
AB  - Sequence profile analysis was used to detect a conserved globular domain in
      several proteins including deltex, Trip12 and poly-ADP-ribose polymerase
      homologs. It was named the WWE domain after its most conserved residues and is
      predicted to mediate specific protein-protein interactions in ubiquitin and ADP
      ribose conjugation systems.

PMID- 11343912
TI  - Type II CAAX prenyl endopeptidases belong to a novel superfamily of putative
      membrane-bound metalloproteases.
AB  - In this article, a novel, large and diverse superfamily of putative membrane
      bound proteins that includes the type II CAAX prenyl endopeptidases is described.
      The majority of the members of this superfamily are hypothetical proteins from
      bacteria and plants. Analysis of the conserved motifs, combined with available
      experimental data, suggests that these proteins are putative metal-dependent
      proteases that are potentially involved in protein and/or peptide modification
      and secretion.

PMID- 11343915
TI  - Landmark drug deal.

PMID- 11343916
TI  - Going round in circles to avoid proteolysis.

PMID- 11343917
TI  - SOD mimic minimizes pain.

PMID- 11343918
TI  - In line for immortality.

PMID- 11343919
TI  - Scientists surveyed.

PMID- 11343920
TI  - Continuous recycling: a mechanism for modulatory signal transduction.
AB  - Modulatory signal transduction commonly requires efficient "on demand" assembly
      of specific multicomponent cellular machines that convert signals to cellular
      actions. This article suggests that for these signaling machines to detect and
      respond to fluctuations in signal strength, they must be continuously
      disassembled in an energy-dependent process that probably involves molecular
      chaperones.

PMID- 11343921
TI  - Signaling at zero G: G-protein-independent functions for 7-TM receptors.
AB  - Eukaryotic cells, whether free-living, single-celled microbes or components of
      complex metazoa, can sense environmental cues through specialized seven
      transmembrane (7-TM) receptors (also called heptahelical or G-protein-coupled
      receptors). 7-TM receptors detect "inputs" such as light, peptide hormones,
      neurotransmitters, pheromones, odorants, morphogens and chemoattractants, linking
      extracellular stimuli to intracellular signaling networks via heterotrimeric G
      proteins. Recently, this obligatory paradigm has been challenged. A growing body
      of evidence indicates that 7-TM receptors can also transmit extracellular signals
      through mechanisms that function independently of G-protein coupling. This review
      discusses pathways and protein interactions for 7-TM receptors signaling "at zero
      G" in Dictyostelium and mammalian cells.

PMID- 11343922
TI  - Cooperative hemoglobins: conserved fold, diverse quaternary assemblies and
      allosteric mechanisms.
AB  - Assembly of hemoglobin subunits into cooperative complexes produces a remarkable
      variety of architectures, ranging in oligomeric state from dimers to complexes
      containing 144 hemoglobin subunits. Diverse stereochemical mechanisms for
      modulating ligand affinity through intersubunit interactions have been revealed
      from studies of three distinct hemoglobin assemblages. This mechanistic
      diversity, which occurs between assemblies of subunits that have the same fold,
      provides insight into the range of regulatory strategies that are available to
      protein molecules.

PMID- 11343923
TI  - Receptor clustering and transmembrane signaling in T cells.
AB  - T cells are activated via engagement of their cell-surface receptors with
      molecules of the major histocompatibility complex (MHC) displayed on another cell
      surface. This process, which is a key step in the recognition of foreign antigens
      by the immune system, involves oligomerization of receptor components. Recent
      characterization of the T-cell response to soluble arrays of MHC-peptide
      complexes has provided insights into the triggering mechanism for T-cell
      activation.

PMID- 11343924
TI  - Glucose-sensing mechanisms in eukaryotic cells.
AB  - Glucose not only serves as a nutrient but also exerts many hormone-like
      regulatory effects in a wide variety of eukaryotic cell types. Recently, interest
      in identifying general mechanisms and principles used to sense the presence of
      glucose has significantly increased and promising advances have been made: in
      yeast, the first proteins with an apparently specific function in glucose
      detection have been discovered; in plant cells, there is increasing evidence for
      a diverse array of glucose-induced signalling mechanisms; and in mammals, glucose
      sensing phenomena have turned out to be much more widespread than just in the
      well-known example of pancreatic beta cells.

PMID- 11343925
TI  - Activation of rhodopsin: new insights from structural and biochemical studies.
AB  - G-protein-coupled receptors (GPCRs) are involved in a vast variety of cellular
      signal transduction processes from visual, taste and odor perceptions to sensing
      the levels of many hormones and neurotransmitters. As a result of agonist-induced
      conformation changes, GPCRs become activated and catalyze nucleotide exchange
      within the G proteins, thus detecting and amplifying the signal. GPCRs share a
      common heptahelical transmembrane structure as well as many conserved key
      residues and regions. Rhodopsins are prototypical GPCRs that detect photons in
      retinal photoreceptor cells and trigger a phototransduction cascade that
      culminates in neuronal signaling. Biophysical and biochemical studies of
      rhodopsin activation, and the recent crystal structure determination of bovine
      rhodopsin, have provided new information that enables a more complete mechanism
      of vertebrate rhodopsin activation to be proposed. In many aspects, rhodopsin
      might provide a structural and functional template for other members of the GPCR
      family.

PMID- 11343926
TI  - Techniques: Recombinogenic engineering--new options for cloning and manipulating
      DNA.
AB  - Driven by the needs of functional genomics, DNA engineering by homologous
      recombination in Escherichia coli has emerged as a major addition to existing
      technologies. Two alternative approaches, RecA-dependent engineering and ET
      recombination, allow a wide variety of DNA modifications, including some which
      are virtually impossible by conventional methods. These approaches do not rely on
      the presence of suitable restriction sites and can be used to insert, delete or
      substitute DNA sequences at any desired position on a target molecule.
      Furthermore, ET recombination can be used for direct subcloning and cloning of
      DNA sequences from complex mixtures, including bacterial artificial chromosomes
      and genomic DNA preparations. The strategies reviewed in this article are
      applicable to modification of DNA molecules of any size, including very large
      ones, and present powerful new avenues for DNA manipulation in general.

PMID- 11343927
TI  - Protein modification by SUMO.

PMID- 11343928
TI  - Connections.

PMID- 11343929
TI  - Photodynamic therapy enhanced by hyperbaric oxygen in acute endoluminal
      palliation of malignant bronchial stenosis (clinical pilot study in 40 patients).
AB  - OBJECTIVES: Photodynamic tumor therapy (PDT) is based upon a photochemical
      reaction that is limited by the availability of molecular oxygen in the target
      tissue. The use of hyperbaric oxygenation (HBO) increases the amount of oxygen
      available for the process may thereby enhance the efficacy of PDT. We proved in a
      prospective, non-randomized clinical pilot study the acute effects on malignant
      bronchial stenosis and the technical feasibility of combined PDT/HBO. METHODS:
      Forty patients (29 males, 11 females, mean age: 64.3 years; range 39-82 years)
      with inoperable, advanced malignant bronchial tumor stenosis were studied
      prospectively. Photosensitization was carried out using a hematoporphyrin
      derivative 2 mg/kg bw 48 h prior to PDT. The light dose was calculated as 300
      J/cm fiber tip. The assessment of outcome 1 and 4 weeks after PDT/HBO was done by
      endoscopy, chest X-ray, spirometry, laboratory parameters, subjective report of
      dyspnea and Karnofsky performance status. RESULTS: At 1 and 4 weeks after the
      treatment the patients felt a significant improvement of dyspnea and hemoptysis
      alongside with an objective subsiding of poststenotic pneumonia, though
      spirometric parameters revealed no significant difference. A significant
      reduction of tumor stenosis (P<0.05) and an improvement of the Karnofsky
      performance status (P<0.05) were documented 1 and 4 weeks after PDT/HBO. No
      therapy related complications were observed. CONCLUSION: Although the small
      number of patients does not allow to draw definitive conclusions, the results
      suggest that combined PDT/HBO represents a new, safe and technically feasible
      approach. It enables efficient and rapid reduction of the endoluminal tumor load
      and helps conditioning the patient for further treatment procedures.

PMID- 11343930
TI  - Prognostic factors in patients with resected pathologic (p-) T1-2N1M0 non-small
      cell lung cancer (NSCLC).
AB  - OBJECTIVES: To clarify prognostic factors in resected pathologic (p-) T1-2N1M0
      non-small cell lung cancer (NSCLC). METHODS: A total of 95 consecutive patients
      who underwent complete tumor resection and mediastinal dissection for pT1-2N1M0
      NSCLC between 1976 and 1997 were retrospectively reviewed. p53 status and
      proliferative activity were evaluated immunohistochemically. RESULTS: The extent
      of N1 stations and p53 status proved to be significant prognostic factors. The 5
      year survival rate for tumor without hilar node (#10) involvement was 66%,
      significantly higher than that for tumor with #10 involvement (39%, P<0.01). The
      5-year survival rate for tumor with aberrant p53 expression was 37%,
      significantly lower than that for tumor without aberrant p53 expression (74%,
      P<0.01). There proved to be no significant difference in the prognosis between
      pT1 disease and pT2 disease; the 5-year survival rates for pT1 and pT2 diseases
      were 62 and 56%, respectively. Age, gender, performance status, grade of tumor
      differentiation, histological type, or proliferative activity were not
      significant factors. Multivariate analysis of prognostic factors using Cox's
      proportional hazard model confirmed these results. CONCLUSIONS: Involvement of
      the hilar node and aberrant p53 expression were significant factors to predict a
      worse prognosis in resected T1-2N1M0 NSCLC.

PMID- 11343932
TI  - The multimodality treatment of thymic carcinoma.
AB  - OBJECTIVES: Thymic carcinoma is a rare neoplasm more invasive and with a poorer
      prognosis than ordinary thymoma. Complete curative resection is sometimes not
      possible, but good response rates to chemotherapy are reported in literature. We
      report our experience with seven cases of thymic carcinoma, who took part to a
      multimodality treatment including neoadjuvant chemotherapy, surgery and post
      operative radiotherapy in our center. METHODS: Since June 1989, seven previously
      untreated patients were enrolled. The primary chemotherapy consisted of three
      courses of cisplatin (P; 75 mg/m(2) i.v., day 1), epidoxorubicin (E; 100 mg/m(2)
      i.v., day 1) and etoposide (VP16; 120 mg/m(2) i.v., days 1, 3 and 5), every 3
      weeks. Surgery was performed following complete hematological recovery. After
      surgery, all patients underwent radiation therapy to the tumor areas, operatively
      marked with clips, at doses of 45 (complete resection) or 60 Gy (incomplete
      resection). RESULTS: The pre-operative diagnosis of thymic carcinoma was
      performed in four cases by a mediastinotomy, and in the remaining cases, by an
      ultrasound-guided (n=2) or a computed tompography-guided (n=1) fine needle
      aspiration. All patients responded (one completely) to the chemotherapy regimen.
      Surgical resection was complete in four cases (histological examination negative
      in one case). Three patients are still alive and well (62-136 months from the
      diagnosis), two are alive with relapse at 16 and 85 months, one patient died at
      86 months from another cause, and one patient died at 18 months from local
      relapse and lung metastases. CONCLUSIONS: A pre-operative shrinkage of the thymic
      carcinoma by means of neoadjuvant multi-drug chemotherapy may improve the
      resectability, and therefore, the survival rate. Our experience, although
      preliminary, is encouraging and merits additional study in a multicenter trial
      with a sufficient number of patients to draw definitive conclusions.

PMID- 11343931
TI  - Prospective study on video-assisted thoracoscopic surgery in the resection of
      pulmonary nodules: 209 cases from the Spanish Video-Assisted Thoracic Surgery
      Study Group.
AB  - OBJECTIVE: The diagnosis of pulmonary nodules has become one of the main
      indications of video-assisted thoracoscopic surgery (VATS), especially for small
      nodules not accessible by bronchoscopy or by percutaneous transthoracic needle
      aspiration. In this study we evaluate the indications, diagnostic safety,
      complications, and technical difficulty of VATS in the diagnosis of pulmonary
      nodules in Spain. MATERIALS AND METHODS: We conducted a prospective study of 209
      patients with one or more pulmonary nodules from a group of Spanish thoracic
      surgery divisions (The Spanish Video-assisted Thoracic Surgery Study Group). Data
      was collected and evaluated on variables contained on a questionnaire including
      demographic information, characteristics of the nodules, identification methods,
      surgical technique, morbidity and mortality rates, and diagnostic yield. RESULTS:
      The mean size of the nodules was 1.9 cm (range 0.3-5 cm). A total of 93.3% were
      peripheral. A diagnosis was established in 100% of the cases. In this study,
      51.1% of lesions were benign and 48.8% were malignant. In 16.3% of cases, a
      conversion to thoracotomy was needed. The morbidity was 9.6% and the mortality
      0.5%. We found a relationship between the size of a nodule and a diagnosis of
      malignancy (P=0.019) and between a central location and a need to convert to
      thoracotomy (P=0.002). Patients with nodules >2 cm had a greater risk of
      complications (P=0.0001). CONCLUSIONS: In the diagnosis of pulmonary nodules,
      VATS has a specificity of 100% and a low mortality rate. The probability of
      developing complications is higher when the nodule is >2 cm.

PMID- 11343933
TI  - Extended thymectomy in myasthenia gravis: a team-work of neurologist, thoracic
      surgeon and anaesthesist may improve the outcome.
AB  - OBJECTIVE: We reviewed our overall experience on 163 patients, affected by
      myasthenia gravis, who underwent thymectomy between 1976 and 1998. A comparison
      between the oldest series of 72 patients (January 1976-December 1992), referred
      by various neurologists and operated on through different approaches, and the
      last 91 patients (January 1993-December 1998), taking part in a strict diagnostic
      therapeutical programme, was made. METHODS: Anagraphic data, duration of
      symptoms, the surgical approach, necessity of respiratory assistance, the
      hospital stay, histopathological findings, preoperative and postoperative
      Osserman classification, as well as medications, were globally analyzed and then
      compared in the two groups. RESULTS: Significant differences in the length of
      hospitalization (8.7 days vs. 4.2 days; P=0.00001) and in the prolonged
      intubation rate (18 vs. 0; P<0.000001) were observed in the most recent series.
      Patients in the pre-operative Osserman stage I and operated on in the second
      period had a higher complete remission rate at the univariate analysis (P<0.001
      and P<0.0001, respectively). At the multivariate analysis the only parameter
      which affected the outcome was to be operated on in the second period (P<0.01).
      CONCLUSIONS: Our experience confirms the role of the extended thymectomy in the
      treatment of myasthenia gravis. Whenever an extended thymectomy was performed
      through a complete sternotomy it was a quick procedure, with short
      hospitalization and acceptable cosmetic results. A careful pharmacological
      control of the myasthenic symptoms and the presence of team-work among
      neurologist, thoracic surgeon and anaesthesist in the peri-operative setting
      reduce the incidence of complications and might increase the efficacy of the
      thymectomy.

PMID- 11343934
TI  - Iliac crest biopsy versus rib segment resection for the detection of bone marrow
      isolated tumor cells from lung and esophageal cancer.
AB  - OBJECTIVE: The presence of isolated tumor cells in the bone marrow affects the
      prognosis of both esophageal cancer and non-small cell lung cancer (NSCLC).
      Therefore, preoperative assessment of isolated tumor cells may be useful to plan
      multimodality treatment. Rib segment resection at surgery provides adequate
      amounts of bone marrow for the detection of isolated tumor cells while bone
      marrow aspirate from the iliac crest does not. The iliac crest biopsy according
      to the Jamshidi technique procures a core of tissue apt for histology and not
      simply for cytology. The aim of this study was to compare the accuracy of iliac
      crest biopsy versus rib segment resection in the diagnosis of isolated tumor
      cells in order to obtain a useful preoperative approach. MATERIAL AND METHODS:
      Twenty-one consecutive patients (18 NSCLC, three esophageal cancer) were
      evaluated. None had chemotherapy prior to evaluation. Bone marrow was obtained
      preoperatively by iliac crest biopsy using the Jamshidi needle and at surgery by
      rib segment resection. Positive cytokeratin neoplastic cells were searched by
      immunohistochemistry on tissue sections from the iliac crest biopsies and by flow
      cytometry on cell suspensions from the rib segments. RESULTS: Isolated tumor
      cells were detected in the rib segments of ten patients. In all cases the
      Jamshidi needle biopsy was not diagnostic. CONCLUSION: Our results suggest that,
      if the diagnosis of bone marrow isolated tumor cells has clinical relevance, the
      preoperative assessment should be performed by rib segment resection or methods
      other than iliac crest aspirate or biopsy. Further investigation is needed to
      determine whether isolated tumor cells have a preferential spread to chest bones
      other than distant bone sites.

PMID- 11343935
TI  - Desmoid tumors of the chest wall.
AB  - OBJECTIVE: Desmoid tumors of the chest wall are uncommon fibromatous tumors
      characterized by their local invasion and frequent recurrences. They are
      considered low-grade malignant sarcomas. We analyze our results and evaluate our
      experience in their surgical treatment. PATIENTS AND METHODS: From 1980 and 1999,
      eight patients were operated in our service for desmoid tumors of the chest wall.
      There were five males and three females with a mean age of 32 years old (17-52
      years). The diagnosis was established on the basis of clinical signs and imaging
      studies (Chest X-ray and computed tomography). Surgery was done by direct
      approach of the tumors. RESULTS: None of the patients had Gardner's syndrome.
      Complete resection was done in seven of the eight cases. Histology confirmed all
      cases. The follow-up ranged from 24 and 180 months, for a mean of 82 months.
      There was one death from cardiac and renal failure 3 months after a fifth
      resection associated with adjuvant radiation therapy. No other post-operative
      complications were observed. Recurrences occurred in 50% of cases, all treated by
      surgery, associated to radiotherapy in one case. CONCLUSION: Surgical treatment
      of primary desmoid tumors of the chest wall requires wide local resection. In
      cases of recurrences, multimodality therapies should be considered.

PMID- 11343936
TI  - Results in surgery for primary and metastatic chest wall tumors.
AB  - OBJECTIVES: Resection of chest wall tumors is often indicated for palliation from
      pain or chronic ulceration. However, under various conditions, it may lead to
      lasting tumor control and substantial freedom of disease might be achieved.
      Therefore, the long-term survival after chest wall resection for primary and
      metastatic tumors and its relation to the underlying histology was analyzed.
      METHODS: The medical files of 82 consecutive patients with tumors of the chest
      wall operated between 1 January 1989 and 31 October 1998 were reviewed. Follow-up
      data were collected from the outpatient's clinic and house physicians,
      respectively. Complete excision was accomplished in 71 patients. In 19 patients,
      partial or complete resection of the sternum was performed. Twenty-eight patients
      underwent chest wall resection extending to intrathoracic structures (lung,
      diaphragm, pericardium). The following subgroups were defined according to the
      histology: (A), sarcoma (n=32); (B), breast cancer (n=22); (C), renal cell cancer
      (n=9); (D), other metastases (n=7); (E), miscellaneous (n=12). The survival
      probability was calculated by the Kaplan-Meier method (SAS software system).
      RESULTS: One of 41 female patients died from postoperative complications on day
      30 after resection of ulcerating breast cancer recurrence (hospital mortality,
      1.2%). The median survival times in groups A-E were 27, 32, 19, 16 and 22 months,
      respectively. CONCLUSIONS: Chest wall resection offers immediate relief in the
      case of severe pain and unpleasant sequelae of ulceration. Moreover, it
      contributes to substantial long-term survival. This, in particular, applies to
      local recurrence after breast cancer.

PMID- 11343937
TI  - Primary chest wall tumors: early and long-term results of surgical treatment.
AB  - OBJECTIVES: A retrospective study of primary chest wall tumors (PCWTs/CWTs) was
      conducted to review their clinical, radiological and pathological features, as
      well as the early and long-term results of surgical management. MATERIALS AND
      METHODS: From 1986 through 1996, 41 patients (18/44% male, 23/56% female, aged 15
      78 years) with PCWTs were treated in our department. RESULTS: Twenty-three
      patients (nine male, 14 female, mean age 36 years) had a benign CWT: enchondroma,
      five patients; fibrous dysplasia, four patients; neurilemmoma, three patients;
      osteochondroma, two patients; granular cell tumor, two patients; fibroma, two
      patients; lipoma, two patients; fibrolipoma, one patient; eosinophilic granuloma,
      one patient; aneurysmal bone cyst, one patient. Eighteen patients (nine male,
      nine female, mean age 59 years) had a malignant CWT: plasmacytoma, five patients;
      chondrosarcoma, two patients; osteosarcoma, two patients; fibrosarcoma, two
      patients; desmoid tumor, two patients; leiomyosarcoma, one patient; malignant
      fibrous histiocytoma, one patient; tendon sheath sarcoma, one patient;
      hemangiosarcoma, one patient; neurinosarcoma, one patient. The ribs were involved
      in 21 patients, the sternum in five patients, and the soft tissue in 17 patients.
      Distinction between benign and malignant CWT was not possible using radiographic
      criteria alone, and diagnosis was always confirmed histologically. Surgical
      treatment consisted of wide resection in 29 patients (15 benign/14 malignant
      CWTs), with the use of synthetic mesh in five cases, and excisional or incisional
      biopsy in 12 patients. There was no perioperative mortality. Two patients with a
      benign CWT (fibroma, one patient; neurilemmoma, one patient) had a local
      recurrence at 13 and 26 months after resection, respectively, and underwent wide
      resection (recurrence rate 8.7%). Follow-up at 3-13 years revealed one non-tumor
      related death in patients with benign CWT (overall mortality rate 4.3%) and no
      other local recurrence. The overall 5- and 10-year survival in patients with
      malignant CWT was 33.3%. CONCLUSIONS: We believe that all CWTs should be
      considered malignant until proven otherwise. Wide resection with tumor-free
      margins is required in order to provide the best chance for cure in both benign
      and malignant lesions.

PMID- 11343938
TI  - Retrograde cerebral perfusion during thoracic aortic surgery and late
      neuropsychological dysfunction.
AB  - OBJECTIVE: Retrograde cerebral perfusion (RCP) is commonly used in thoracic
      aortic surgery, ostensibly to provide metabolic support, maintain cerebral
      hypothermia and/or wash out particulate emboli. We tested the hypothesis that RCP
      would affect neuropsychological outcome in a clinical cohort. METHODS: Ninety
      four patients undergoing elective thoracic aortic repairs requiring deep
      hypothermic circulatory arrest consented to participate in this study. These
      patients underwent preoperative neuropsychological evaluation and comprise the
      reference group. Fifty-six of these patients also underwent neuropsychological
      evaluation several weeks postoperatively, 12 of whom (21%) had RCP. The
      neuropsychological domains tested were attention, processing speed, memory,
      executive function, and fine motor function. A global assessment of impairment,
      negative neuropsychological outcome (NNO), was defined as a postoperative
      decrease in function in two or more neuropsychological domains for patients with
      at least three domains tested both pre- and postoperatively (n=48). The
      relationship of three potential predictors (RCP, cerebral ischemia time and
      patient age) to negative outcomes was analyzed using Wilcoxon two-sample tests,
      chi(2) tests, Mantel-Haenszel tests and multiple logistic regression. P<0.05 was
      considered significant. RESULTS: Memory dysfunction and NNO had strong
      associations with RCP. This effect remained significant when controlling
      separately for age and cerebral ischemia time. CONCLUSIONS: The effects of RCP
      are difficult to distinguish from those of age and prolonged cerebral ischemia
      time, because complex thoracic aortic repairs are associated with advanced age,
      prolonged cerebral ischemia and use of RCP. Despite this limitation, these
      preliminary data indicated that RCP had no beneficial effect (and most likely a
      negative effect) upon cognitive outcome.

PMID- 11343939
TI  - Mid-term follow-up of aortic root remodelling compared to Bentall operation.
AB  - OBJECTIVES: Aortic valve sparing with root remodelling has proven useful in cases
      of aortic regurgitation secondary to ascending aorta disease. An excessive rate
      of re-operation for recurrent aortic regurgitation after this conservative
      approach might compensate the prosthesis-related risk of the Bentall operation.
      METHODS: From January 1995 to September 2000, 69 consecutive patients with aortic
      expansive aneurysm and concomitant aortic valve disease, were submitted to the
      Bentall operation (group A, n=37) in the presence of an abnormal valve, or to
      root remodelling (group B, n=32) in cases of secondary aortic incompetence. One
      patient in group A and four in group B had Marfan syndrome. The follow-up was
      1021 patient-months (range, 1-68 months) in group A and 926 in group B (1-64
      months). The event-free survival was calculated using the Kaplan-Meier method,
      and the difference between curves was evaluated using the Mantel-Cox log-rank
      test. RESULTS: The operative mortality was 5% in group A and 0% in group B. One
      patient died at follow-up in group A and none in group B. Four patients (three
      Marfan) in group B were re-operated on because of recurrent aortic regurgitation.
      The 5-year event-free survival was 88+/-7% in group A and 82+/-8% in group B
      (P=0.58). Early residual aortic regurgitation remained stable over time only in
      patients with good early results. CONCLUSIONS: Mid-term follow-up failed to
      reveal statistically significant differences in the clinical outcome between
      remodelling and the Bentall operation. Our results support the widespread use of
      root remodelling, provided that an indication to this conservative approach is
      achieved after careful, case-by-case evaluation. A good early operative result is
      likely to remain stable over time.

PMID- 11343940
TI  - Chronic beta-blocker therapy improves outcome and reduces treatment costs in
      chronic type B aortic dissection.
AB  - OBJECTIVES: To compare the medical treatment of chronic type B aortic dissection
      with beta-blockers versus other antihypertensive treatments in terms of their
      requirement for surgical intervention and treatment costs. METHODS: Case records
      of the 130 patients treated for aortic dissection type B in this unit between
      1988 and 1997 were reviewed. Seventy-eight of 130 patients with chronic
      dissection have received isolated medical treatment. Seventy-one of 78 patients
      were discharged alive. Fifty-one of 71 received beta-blocker treatment, 20/71
      were treated with other antihypertensive drugs. RESULTS: Surgery for aortic
      dissection became necessary in 20/71 patients (28%) during follow-up (mean, 4.2
      years): 10/51 in the beta-blocker group and 9/20 in the other antihypertensive
      drug group. The freedom from subsequent aortic operation was 80 and 47%,
      respectively (P=0.001). Indications for emergency surgery were increased aortic
      diameter (79%), symptomatic aortic aneurysm (11%), and renal artery hypoperfusion
      (5%). The median hospitalization time during follow-up (dissection-related) was 2
      days for patients who received beta-blockers and 16 days for patients who
      received other antihypertensive drug treatments (P=0.001). The cost of
      treatment/patient per year amounted to 644 and 12748 euros, respectively.
      CONCLUSIONS: A substantial proportion of patients with chronic type B dissection
      who receive initial medical management will later need surgery. Long-term
      treatment with beta-blockers reduces the progression of aortic dilatation, the
      incidence of subsequent hospital admissions, as well as the incidence of late
      dissection-related aortic procedures and the cost of treatment. Patients with
      chronic type B dissection need, in addition to frequent follow-up of aortic
      diameter, continuous treatment with beta-blocking agents.

PMID- 11343941
TI  - Neurological injury after surgery for ischemic heart disease: risk factors,
      outcome and role of metabolic interventions.
AB  - OBJECTIVES: Neurological complication remains a feared and increasing problem in
      association with cardiac surgery. The aim of this study was to analyze risk
      factors for neurological complications in a cohort of patients in whom inotropes
      for weaning from cardiopulmonary bypass was gradually replaced by metabolic
      treatment. METHODS: The records of 775 consecutive patients undergoing coronary
      artery bypass grafting (CABG) or combined CABG+valve procedures were examined.
      Forward stepwise multiple logistic regression analysis was used for statistical
      evaluation of independent risk factors. RESULTS: The incidence of neurological
      injury was 1.8% in patients undergoing isolated CABG and 5.4% after combined
      CABG+valve procedures. After cross-validation multivariate analysis identified
      history of cerebrovascular disease, advanced age and aortic cross-clamp time as
      independent risk factors for postoperative cerebral complications. Chronic
      obstructive pulmonary disease and number of bypasses also emerged as risk factors
      in the primary analysis. CONCLUSIONS: In general, markers for advanced
      atherosclerosis, with history of cerebrovascular disease as the most important,
      emerged as predictors for neurological injury. Although it did not enter the
      final risk model, the results also suggest that postoperative heart failure
      deserves further surveillance as a potential risk factor for neurological
      complications. However, no evidence for untoward neurological effects associated
      with glutamate or glucose-insulin-potassium treatment was found.

PMID- 11343942
TI  - Should severe monolateral asymptomatic carotid artery stenosis be treated at the
      time of coronary artery bypass operation?
AB  - OBJECTIVE: The optimal treatment of severe monolateral asymptomatic carotid
      artery stenosis (SMACS) in patients undergoing coronary artery bypass grafting
      (CABG) is still controversial. MATERIALS AND METHODS: This study is based on the
      in-hospital and mid-term (>5 years) clinical results of a cohort of 139
      consecutive CABG patients with SMACS operated at our Institution between January
      1989 and December 1995. In the first 73 patients (no carotid surgery group), the
      SMACS was left untouched at the time of coronary surgery, whereas in the
      remaining 66 (carotid endoarterectomy group), the carotid stenosis was treated
      either immediately before or concomitantly with the CABG procedure (depending on
      the severity of the anginal symptoms). RESULTS: The overall preoperative
      characteristics of the patients were comparable. The in-hospital results were
      similar between the two groups with regard to mortality, stroke and major
      postoperative complications. However, at mid-term follow-up, significantly more
      patients of the no carotid surgery group suffered cerebral events (transient or
      permanent) ipsilateral to the SMACS or the lesion had to be operated on.
      CONCLUSIONS: The concomitant treatment (either staged or simultaneous) of SMACS
      at the time of CABG does not influence the in-hospital results, but confers
      significant neurological protection during the years after the operation.

PMID- 11343943
TI  - Stroke during coronary bypass surgery: principal role of cerebral macroemboli.
AB  - OBJECTIVE: The purpose of this study was to gain insight into the etiology of
      stroke during coronary bypass surgery. METHODS: Retrospective review of
      prospectively gathered data on 6682 consecutive coronary bypass patients.
      Patients undergoing simultaneous procedures, including carotid endarterectomy,
      were excluded. We performed a systematic chart review of all patients who
      suffered a perioperative stroke. Predictors of stroke were determined with
      stepwise logistic regression analysis. RESULTS: The prevalence of stroke was 1.5%
      (n=98). Stroke patients had significantly increased intensive care unit and
      hospital length of stays, as well as increased mortality when compared to
      patients without stroke (all P< 0.001). Independent predictors of stroke were (in
      decreasing order of magnitude): age >70 years, left ventricular ejection fraction
      <40%, previous stroke or transient ischemic attack, normothermic cardiopulmonary
      bypass, diabetes, and peripheral vascular disease. Chart review revealed that the
      probable cause of stroke was macroemboli, likely from ascending aorta
      atherosclerosis, in 37% of patients and unknown in 38% of patients. Computerized
      tomography (CT) scans were obtained in 79 patients (81%). Lesions detected by CT
      were consistent with a macroembolic etiology: nearly all lesions were ischemic in
      nature and located in the distribution of major cerebral arteries, particularly
      the middle cerebral artery. CONCLUSIONS: Stroke is a devastating complication of
      coronary bypass surgery. Our multivariable risk factors for stroke, chart review,
      and CT findings all suggest that macroemboli, presumably from the ascending
      aorta, are the predominant cause of stroke during coronary bypass surgery. Future
      studies should be directed at minimizing the risk of embolization during cardiac
      surgery.

PMID- 11343944
TI  - Na(+)/H(+)-exchange inhibition and aprotinin administration: promising tools for
      myocardial protection during minimally invasive CABG.
AB  - OBJECTIVE: Minimally invasive coronary artery bypass grafting (CABG), carried out
      on the warm beating heart, does not allow conventional myocardial protection. The
      objective was to investigate the possibility of enhancing tolerance to ischemia
      during short episodes of coronary artery occlusion, based on a pharmacological
      approach using a selective Na(+)/H(+)-exchange inhibitor (cariporide) or a serine
      protease inhibitor (aprotinin). METHODS: Four groups (n=6 in each group) of sheep
      were subjected to 20 min of normothermic regional ischemia (first lateral branch
      of the circumflex artery occlusion) followed by 1 h of reperfusion. Regional wall
      thickening was measured using sonomicrometry, and expressed as the percentage of
      thickening fraction compared with baseline. Group I was the control with no
      treatment, group II received cariporide (1 mg/kg administered over 2 min prior to
      ischemia), group III was treated with aprotinin (2.10(6) kallikrein inactivation
      units (KIU) load followed by 500.000 KIU/h). Group IV was treated with a
      combination of cariporide and aprotinin at the same concentrations as in groups
      II and III, respectively. RESULTS: Wall thickening measurements showed that,
      compared with control, cariporide was largely able to suppress secondary loss of
      wall thickening after initial recovery during early reperfusion. Wall thickening
      in the ischemic/reperfused myocardial area improved from 10+/-31 to 51+/-17% at 1
      h of reperfusion (P=0.002). Aprotinin improved wall thickening at the end of 1 h
      of reperfusion to 70+/-13% (P=0.0001). However, in this group, there was a
      transient loss of regional contractility similar in amplitude and time course to
      the one observed in the control group. A combination of cariporide and aprotinin
      suppressed transient contractile loss and resulted in improved wall thickening at
      the end of 1 h of reperfusion (65+/-22%, P=0.0002 vs. control). This value was
      not significantly different from the cariporide (P=0.263) or aprotinin (P=0.704)
      group. CONCLUSION: These data indicate that both Na(+)/H(+)-exchange inhibition
      and aprotinin administration are promising tools for cardioprotection during
      minimally invasive CABG. A combination of both treatments is able to adequately
      suppress loss of contractility during early reperfusion as a consequence of
      reperfusion injury, and results in significantly improved wall thickening at the
      end of 1 h of reperfusion.

PMID- 11343945
TI  - Cold continuous antegrade blood cardioplegia: high versus low hematocrit.
AB  - OBJECTIVE: Cold continuous antegrade blood cardioplegia (CCABCP) is used with
      different hematocrit values. We investigated the consequences of CCABCP with low
      hematocrit (LH: 20-25%) versus high hematocrit (HH: 40-45%). METHODS:
      Anesthetized open chest pigs (25 kg) were placed on cardiopulmonary bypass (CPB).
      The hearts were arrested for 30 min by 6 degrees C CCABCP with either LH or HH
      (n=8, each): After an initial 3 min application of high potassium (20 mEq) BCP
      the hearts were arrested for subsequent 27 min by normokalemic 6 degrees C cold
      blood delivered continuously antegradely. Thereafter the hearts underwent
      perfusion with warm systemic blood for an additional 30 min on CPB. Biochemical
      cardiac data (MVO(2) (ml min(-1)100 g(-1)), release of creatine kinase (CK; units
      min(-1)100 g(-1))) and lactate (mg min(-1)100 g(-1))) and the coronary vascular
      resistance index (CVRI (mmHg ml(-1)ming)) were measured during CPB. Total tissue
      water content (%) and left and right ventricular stroke work indices (LV-and RV
      SWI (g m kg(-1))) were assessed 30 min after discontinuation of CPB and compared
      to pre-CPB controls. RESULTS: The hearts of the LH group had no biochemical or
      functional disturbance. The HH group showed marked CK leakage (0.6+/-0.2* vs.
      0.1+/-0.1, *P<0.05 for comparison of LH vs. HH with Student's t-test for unpaired
      data), impaired initial oxygen consumption (4+/-1* vs. 7+/-1) after cardiac
      arrest, an increased CVRI (82+/-12* vs. 50+/-8), the formation of myocardial
      edema (81.0+/-1.3* vs. 77.5+/-1.2), and poor functional recovery (LVSWI 0.2+/
      0.1* vs. 1.0+/-0.1; RVSWI 0.1+/-0.1* vs. 0.5+/-0.1). The absence of lactate
      production in both groups was in accord with the non-ischemic protocol.
      CONCLUSIONS: CCABCP with a low hematocrit of 20-25% is cardioprotective. In
      contrast, CCABCP with a high hematocrit of 40-45% jeopardizes the heart despite
      avoiding ischemic periods, and should be avoided.

PMID- 11343946
TI  - Ultra-short-acting cardioselective beta-blockade attenuates postischemic cardiac
      dysfunction in the isolated rat heart.
AB  - OBJECTIVES: We sought to test the effectiveness of ultra-short-acting
      cardioselective beta-blockade, landiolol hydrochloride, for warm heart surgery.
      METHODS: The isolated perfused rat heart preparation was used. After preischemic
      measurement of cardiac function, 3 min of coronary infusion of crystalloid
      cardioplegic solution (37 degrees C) with landiolol hydrochloride of various
      concentrations (1, 2.5, 5, and 10 mmol/l) or without it (control group) was
      performed, followed by 30 min of warm ischemic arrest. Finally, postischemic
      function was measured. RESULTS: The percentage recoveries of heart rate in hearts
      receiving 0, 1, 2.5, 5, and 10 mmol/l landiolol hydrochloride were 89.4+/-3.4%,
      90.9+/-1.7%, 89.6+/-1.8%, 83.4+/-3.3%, and 74.3+/-1.9% (P<0.05 vs. 0, 1, and 2.5
      mmol/l groups), respectively. The percentage recoveries of aortic flow were
      55.6+/-3.1%, 62.8+/-3.3%, 75.0+/-4.2% (P<0.05 vs. 0 and 10 mmol/l groups), 65.3+/
      5.3%, and 51.6+/-4.0%, respectively. Similar recovery profiles were observed with
      the first derivative of the rise in aortic pressure, stroke volume and stroke
      work. The total amount of coronary effluent in the hearts receiving 5 or 10
      mmol/l was lower than in the other groups. CONCLUSIONS: Landiolol hydrochloride
      has the potential to enhance postischemic cardiac function after the warm
      cardioplegic arrest. The optimal concentration for maximum postischemic
      functional recovery was 2.5 mmol/l, and recoveries of aortic flow and heart rate
      decreased in hearts receiving 5 mmol/l or more.

PMID- 11343947
TI  - Quantitative measurement of endothelium derived nitric oxide production of the
      internal mammary artery bypass graft during extracorporeal circulation.
AB  - OBJECTIVE: This study was undertaken to determine the extent of endothelium
      derived nitric oxide (EDNO) production of the internal mammary artery (IMA)
      bypass graft and of the native coronary circulation by measuring its stable
      metabolite (NO2: nitrite) in different sampling sites: internal mammary free cut
      end flow, in the coronary sinus prior and after anastomosis completion, and to
      compare them to the nitrite level of the normal plasma. METHODS: Nitrite level
      was determined with fluoroscopy using 4 hydroxycoumarin nitrozation in 50
      consecutive patient undergoing onpump myocardial revascularization. RESULTS:
      Nitrite levels in the normal plasma were found to be 31.2 micromol. Nitrite level
      in systemic and coronary circulation after total heparinization, prior to
      extracorporeal circulation (ECC) was found to be 60.8 micromol (lower quartile
      /l.q./: 46.6 micromol, upper quartile /u.q./: 70.0 micromol,) and 58.3
      micromol,(l.q.:47.8 micromol, u.q.:70.0 micromol) respectively, and of the IMA
      bypass graft free cut end flow was 54.4 micromol,(l.q.:42.0 micromol, u.q.:66.8
      micromol) while in the coronary sinus, after completion the IMA anastomosis, it
      was 45.71 micromol (l.q.: 35.0 micromol, u.q.: 55.0 micromol), (all geometric
      mean). CONCLUSIONS: Total heparinization enhances EDNO production. Nitrite
      concentration in the IMA free cut end flow is similar or greater, than that of
      the native coronary circulation, however, after IMA bypass graft construction
      significant reduction (P<0.001) could be measured in the coronary sinus.

PMID- 11343948
TI  - Coronary artery bypass grafting surgery without the routine application of blood
      products: Is it feasible?
AB  - OBJECTIVE: Fresh frozen plasma (FFP) substitution is currently standard practise
      in cardiac surgery. In this study we investigate whether elective coronary artery
      bypass grafting (CABG) surgery is feasible without the administration of blood
      products compared to the substitution of fresh frozen plasma. PATIENTS AND
      METHODS: From September 1997 to April 1998, 120 consecutive patients underwent
      CABG surgery at our institution. In the FFP group patients (n=60; men, n=43;
      women, n=17; mean age: 64+/-8.5 years) received 4 units of fresh frozen plasma
      (FFP) intraoperatively. In comparison, patients in the control group (n=60; men,
      n=44; women, n=16; mean age: 65+/-7.5 years) did not receive FFP. Main endpoints
      included perioperative hematologic parameters, blood loss, and the amount of
      blood products that were administered. RESULTS: Intraoperatively, the
      substitution of packed red blood cells (pRBC) in the FFP group was significantly
      higher compared with the control group (0.63+/-0.94 units/patient vs. 0.12+/-0.38
      units/patient, P=0.001). Postoperatively, patients in the FFP group required
      significantly more pRBC products than patients in the control group (0.78+/-1.09
      vs. 0.42+/-0.77, P=0.024). There were no significant differences in hemoglobin
      (FFP group: 99+/-11.1 g/dl; control group: 105+/-13.5 g/dl) and hematocrit levels
      (FFP group: 30+/-3.39%; control group: 32+/-4%). Also, no significant differences
      regarding the postoperative blood loss was observed between groups (FFP group:
      588+/-224 vs. control group: 576+/-272 ml/24 h). CONCLUSIONS: This study clearly
      demonstrates that the avoidance of routine intraoperative FFP administration does
      not lead to an increase in blood loss postoperatively compared to patients that
      received FFPs. Furthermore, we did not observe increased requirements for
      postoperative FFP infusion in patients that did not receive FFPs
      intraoperatively.

PMID- 11343949
TI  - Severe obesity does not adversely affect perioperative mortality and morbidity in
      coronary artery bypass surgery.
AB  - OBJECTIVE: Obese patients are usually thought to have an increased risk for
      complications in coronary artery bypass surgery. METHODS: Therefore, the data of
      500 consecutive patients undergoing coronary artery bypass grafting at our
      department in 1998 by use of cardiopulmonary bypass were analyzed. Severe obesity
      was defined as body mass index (BMI) > or = 30.0 kg/m(2). Obese patients (n=100;
      group O) were compared to the remaining 400 patients (group C). Both groups were
      comparable with respect to sex, history of prior myocardial infarction, chronic
      obstructive pulmonary disease, previous stroke, duration of cardiopulmonary
      bypass, aortic cross-clamp time and number of distal anastomoses performed. Obese
      patients were slightly younger and diabetes and hypertension were more common in
      these patients. RESULTS: Survival and potential complications including
      perioperative myocardial infarction, sternal wound infection, wound infection at
      the leg, renal failure, stroke, prolonged mechanical ventilation, pneumonia,
      reexploration for bleeding, and atrial arrhythmias were analyzed. No significant
      differences between obese and non-obese patients were detected. CONCLUSION:
      Severe obesity does not necessarily adversely affect perioperative mortality and
      morbidity in patients undergoing coronary artery bypass grafting in this study.

PMID- 11343950
TI  - Pulmonary valve insertion late after repair of Fallot's tetralogy.
AB  - OBJECTIVES: To analyze the results of pulmonary valve insertion late after
      initial repair of Fallot's tetralogy. Pulmonary insufficiency (PI) after
      correction of Fallot's tetralogy is usually well tolerated in the short term, but
      is associated with symptomatic right ventricular dilatation and an increased risk
      of ventricular arrhythmias over longer periods of time. METHODS: From 1993 to
      July 2000, 51 patients were reoperated for PI at a mean age of 25.7+/-11.9 years.
      The mean age at initial repair was 6.4+/-7.2 years. Patients with a conduit
      inserted at initial operation, with absent pulmonary valve syndrome or with a
      more than moderate ventricular septal defect at reoperation were excluded from
      the study. A cryopreserved pulmonary (96%) or aortic (4%) homograft was implanted
      in the orthotopic position with the use of cardiopulmonary bypass 19.3+/-9.1
      years (2.7-40.3 years) after initial correction. Preoperative symptoms (New York
      Heart Association, NYHA class), degree of PI (echo-Doppler, MRI), right
      ventricular dimensions (MRI) and QRS duration were compared to findings at last
      follow-up. RESULTS: Follow-up is complete and had a mean duration of 1.7+/-1.4
      years. Hospital mortality was 2%. No serious morbidity occurred. Severe PI was
      present preoperatively in all patients. At last follow-up echo-Doppler studies
      showed PI to be absent or trivial in 96% and mild in 4% of patients. In 13
      patients MRI studies were performed both pre- and postoperatively: in this group
      PI was reduced from a mean of 48 to 4%. After 6 months NYHA capacity class had
      improved significantly from 2.3+/-0.6 to 1.4+/-0.5. After 1 year end-diastolic
      and end-systolic right ventricular volumes were reduced significantly. Right
      ventricular ejection fraction and QRS duration remained unchanged. CONCLUSIONS:
      PI late after correction of Fallot's tetralogy may lead to serious symptomatic
      right ventricle dilatation. After pulmonary homograft insertion right ventricular
      dimensions decrease rapidly and functional improvement is observed in almost all
      patients.

PMID- 11343951
TI  - Single ventricle with systemic obstruction in early life: comparison of initial
      pulmonary artery banding versus the Norwood operation.
AB  - OBJECTIVES: The outcomes of initial pulmonary artery banding (PAB)+/-coarctation
      repair are compared with the Norwood operation in newborns with single ventricle
      (SV) and systemic obstruction (SO). METHODS: Between January 1987 and July 2000,
      22 patients (median age, 12 days) with SV and aortic arch obstruction (AAO),
      subaortic stenosis (SAS), or both underwent surgery. Two initial surgical
      approaches were used: PAB+/-coarctation repair (group I, seven patients); Norwood
      type operation (group II, 15 patients). RESULTS: The overall mortality was 32%
      (seven of 22 patients). There was no late mortality. The mortality in group I was
      43% versus 27% in group II. Recently, there has been no mortality following the
      Norwood operation in the last eight patients operated since 1995. Of the
      survivors, nine patients have undergone the Fontan operation and four patients
      have had the bidirectional Glenn (BDG) with no deaths. There was one repair of
      supravalvar aortic stenosis at the time of BDG in group II as opposed to eight
      reinterventions for SAS and/or AAO in four patients in group I (P=0.01).
      CONCLUSIONS: PAB+/-coarctation repair for SV and SO is associated with a high
      mortality and a high reoperation rate for SAS or recurrent AAO. Although the
      Norwood operation was also associated with a high mortality early on, it can now
      be performed with excellent outcome. This improvement, combined with a low
      reintervention rate for SAS or AAO, suggests that the Norwood operation is likely
      to emerge as the procedure of choice for SV and SO.

PMID- 11343952
TI  - Reliable long-term non-pulsatile circulatory support without anticoagulation.
AB  - OBJECTIVE: The Terumo implantable left ventricular assist system (T-ILVAS)
      consists of a titanium centrifugal pump with a unique magnetically suspended
      impeller producing continuous (non-pulsatile) flow up to 10 l/min. The interior
      surface is heparin-coated and there is no purge system. We implanted the device
      into six sheep to ascertain in-vivo haemodynamic function, mechanical reliability
      and biocompatibility. METHODS: The T-ILVAS was implanted via left thoracotomy
      without cardiopulmonary bypass. The inflow cannula was placed in the left
      ventricular apex and a Dacron outflow graft anastomosed to the descending aorta.
      All animals recovered well. No anticoagulation (heparin or warfarin) was given
      after the surgery. Suspension position, motor current, impeller speed and pump
      flow were continuously monitored and stored by on-line computer. Serial blood
      samples were collected to determine haematological and biochemical indices of
      renal function, liver function and haemolysis. All animals were electively
      euthanized between 3 and 7 months postoperatively. The explanted pumps were
      examined for mechanical reliability and thrombus formation. Major organs were
      examined macroscopically and histologically for thromboembolism. RESULTS: All
      animals appeared completely normal for up to 210 days. At speeds between 1500 and
      2000 rev./min the device pumped up to 8 l/min capturing all mitral flow. There
      were no major complications (pump failure, thromboembolism, haemorrhage, or
      driveline infection). Indices of haemolysis, liver and renal function remained
      within normal limits. All pumps were mechanically sound and free from thrombus.
      One embolus was found in a sectioned kidney. CONCLUSION: The T-ILVAS successfully
      supported the systemic circulation without anticoagulation for up to 210 days.
      Mechanical reliability and biocompatibility were demonstrated. Organ function
      remained within normal limits during continuous non-pulsatile flow.

PMID- 11343953
TI  - Left ventricle restoration in patients with non-ischemic dilated cardiomyopathy:
      risk factors and predictors of outcome and change of mid-term ventricular
      function.
AB  - OBJECTIVE: The partial left ventriculectomy (PLV) for end-stage dilated
      cardiomyopathy (DCM) which worked in some patients has been reported, although
      the hospital mortality is high. To reduce hospital mortality, we selected
      operative procedures of left ventricular (LV) restoration to improve the
      operative results. We analyzed the risk factors and predictors of outcome, and
      the mid-term changes of the LV function were determined. PATIENTS AND METHODS:
      Between December 1996 and September 2000, 74 patients with non-ischemic DCM
      received LV restoration. The age ranged from 14 to 76 years (mean, 49.0+/-14.0
      years), and there were 63 men and 11 women. The etiology of the DCM was
      idiopathic DCM in 49 patients, and dilated hypertrophic cardiomyopathy in seven
      patients and others in 18. The preoperative New York Heart Association (NYHA)
      functional class was 29 in class III and 45 in class IV, in which 32 patients
      depended on inotropic support. PLV or septal anterior ventricular exclusion
      (SAVE) was selected depending on the akinetic lesion of the LV based on the
      intraoperative echo-test. Fifty-six patients received elective operations, and
      emergency operations were performed in 18 patients. The risk factors and
      predictors of outcome were analyzed in 74 patients, and in 35 patients who
      survived more than 1 year after receiving LV restoration, the mid-term cardiac
      function was examined by cardiac echogram and catheterization. RESULTS: PLV was
      performed in 62 patients and SAVE in 12 patients. Concomitant mitral surgery was
      performed in 66 patients (89%) and tricuspid annuloplasty in 42 patients (57%).
      There were 15 hospital deaths and 13 patients died after discharge from the
      hospital (cardiac deaths in nine and non-cardiac deaths in four). In the 46 late
      survivors, the NYHA class was I or II in 42 patients and III in four patients.
      Selection of the procedure of LV restoration (P<0.01), elective operation
      (P<0.05), and the preoperative volume of LV (endodiastolic volume index of <180
      ml/m(2); P<0.05) were risk factors and predictors influencing hospital and late
      death. After the operation, the LV function improved significantly and the
      improvement was maintained at the mid-term period; the LV ejection fraction was
      31.8+/-7.9% (P<0.01) at 1 year from 23.0+/-7.3% preoperatively, left ventricular
      diastolic diameter was 62.8+/-10.9 (P<0.01) from 81.7+/-8.2 mm and the LV
      endosystolic volume index was 88.5+/-45.8 (P<0.05) from 162.6+/-41.6 ml/m(2).
      CONCLUSIONS: The operative results improved with the selection of the procedures,
      with elective operation, and mitral plasty for less cardiac dilatation. The mid
      term results of clinical status and LV function showed the effectiveness of the
      operation.

PMID- 11343954
TI  - Tacrolimus as a rescue immunosuppressant after heart transplantation.
AB  - OBJECTIVE: The purpose of this retrospective study is to review our experience
      with tacrolimus as a rescue immunosuppressant for heart transplant recipients
      with refractory rejection or cyclosporine intolerance. METHODS: From June 1995 to
      November 1998, 15 cardiac transplant recipients were converted from our standard
      cyclosporine-based immunosuppressive regimen to a tacrolimus-based treatment.
      Each patient had been treated with cyclosporine, azathioprine and steroids. Six
      were switched to tacrolimus for persistent rejection, four for recurrent acute
      rejection and five for severe debilitating side-effects attributed to
      cyclosporine. All ten patients converted to tacrolimus because of rejection had
      been treated with high-dose methylprednisolone intravenously and four had also
      received anti-lymphocyte globulin (ALG; one patient) or anti-thymocyte globulin
      (ATG; three patients) preparations. RESULTS: The time between transplantation and
      conversion to tacrolimus ranged from 44 to 1866 (median, 380) days. The range of
      follow-up after conversion was 84-1379 (median, 806) days. Eleven patients are
      alive with a follow-up period of 764+/-435 (median, 820) days. Four patients died
      between 90 and 930 (median, 464) days after conversion. The average number of
      episodes of acute rejection/recipient decreased from 2.1+/-1.6 on the
      cyclosporine regimen to 0.2+/-0.4 on the tacrolimus regimen (P<0.001). When the
      incidence of acute rejection was normalized for follow-up times (episodes/100
      patient-days), the results were 1.1+/-1.4 and 0.07+/-0.2, respectively (P<0.01).
      The persistent/recurrent rejection resolved in all ten patients who were
      converted to tacrolimus. None of the five cyclosporine intolerant patients
      converted to tacrolimus experienced rejection after the changeover. CONCLUSIONS:
      In our experience, conversion from a cyclosporine-based to a tacrolimus-based
      maintenance immunosuppression has been shown to be an effective and safe approach
      to the management of patients with persistent or recurrent cardiac allograft
      rejection or those with cyclosporine intolerance.

PMID- 11343955
TI  - Neoplastic disease after heart transplantation: single center experience.
AB  - OBJECTIVES: Mandatory use of prolonged immunosuppression in organ transplantation
      is complicated by an increased incidence of cancer. The current study represents
      a retrospective analysis of the incidence of neoplasms in our heart
      transplantation program. METHODS: Four-hundred and seventy-four patients (403
      male and 71 female; mean age, 48.6+/-12.1 years), with at least 30 days of follow
      up, were enrolled in this study. Patients received triple immunosuppression with
      cyclosporin A, azathioprine and steroids. Moreover, as a prophylactic anti
      lymphocyte therapy, 388 patients (82%) were administered RATG, 67 patients (14%)
      received ALG and 19 patients (4%) OKT3. The mean follow-up time was 71.1+/-43.0
      months. RESULTS: Fifty-five patients (11.6%) developed malignant neoplasms. The
      cancer frequencies were: solid tumors, 55%; non-Hodgkin lymphomas (NHL), 20%;
      Kaposi's sarcomas, 11%; skin cancers, 9%; undifferentiated sarcomas and myelomas,
      5%. Solid tumors mainly affected the lung (39%), bowel (16%), stomach (6.5%),
      liver (6.5%), pancreas (6.5%) and oral cavity (6.5%). The times to the onset of
      cancer from transplantation were: Kaposi's sarcoma, 12.7+/-16.8 months; skin
      cancers, 34.5+/-23.8 months; solid tumors, 54.3+/-38.7 months; NHL, 60.1+/-36.4
      months; undifferentiated sarcomas and myelomas, 90.0+/-15.6 months. As determined
      by univariate and multivariate analyses, sex, number of treated rejections,
      previous history of tumor, average dose of cyclosporine and prednisone and
      cyclosporine blood levels did not increase the incidence of malignancies.
      Univariate analysis suggests a significant correlation between the type of
      prophylactic immunoglobulins and the average dose of azathioprine with the
      incidence of neoplasms. Both univariate and multivariate analyses demonstrated a
      significant correlation between patient's age at the time of transplantation and
      risk of cancer occurrence (risk increased by 1.074/year; P=0.0056 with
      multivariate Cox regression). CONCLUSIONS: Cancer is a strong limitation for long
      term survival after heart transplantation. The only risk factor recognized is the
      patient's age at the time of transplant. Furthermore, the type of prophylactic
      globulins used for induction therapy and some specific immunosuppressant agent
      (azathioprine) may play a significant role in the development of malignancies
      after transplantation.

PMID- 11343956
TI  - Conditions of vector delivery improve efficiency of adenoviral-mediated gene
      transfer to the transplanted heart.
AB  - OBJECTIVES: Conditions for ex vivo gene transfer to the transplanted heart were
      studied in a model of syngeneic abdominal heterotopic heart transplantation in
      the rat. Various methods of adenoviral-mediated gene transfer to the transplanted
      heart were compared. METHODS: In the first experiment, a dose response study, an
      adenoviral vector encoding the beta-galactosidase gene was infused into the donor
      heart with the pulmonary artery open and flushed out prior to performing the
      transplant. In the second experiment, the effects of clamping the pulmonary
      artery during vector infusion and not flushing out the viral solution, resulting
      in vector dwell during the warm ischemia, were examined. RESULTS: In the first
      experiment, gene transfer was relatively inefficient; however, transgene
      expression improved with increases in the vector dose (range, 1x10(7)-1x10(9)).
      The efficiency of gene transfer was significantly greater when the conditions of
      the second experiment were applied. In all models studied, cardiomyocytes and not
      vascular endothelial cells were the predominant cell type transduced.
      CONCLUSIONS: This study indicates that the conditions of adenoviral vector
      delivery are critical for optimizing gene transfer in the transplant setting. In
      addition, intravascular administration of adenoviral vector to the donor heart
      results predominantly in cardiomyocyte transgene expression.

PMID- 11343957
TI  - Surgical technique to avoid circulatory arrest and direct arch vessel cannulation
      during neonatal aortic arch reconstruction.
AB  - Deep hypothermic circulatory arrest (DHCA) has been used routinely for surgery
      involving the aortic arch. Recently, techniques have been developed that avoid
      circulatory arrest and maintain low-flow cerebral perfusion (LFCP) in an attempt
      to avoid the potential neurological sequelae associated with DHCA. We describe a
      technique of LFCP that avoids circulatory arrest and direct cannulation of the
      arch vessels. Five patients underwent reconstruction of the aortic arch with
      concomitant biventricular intracardiac repair. The distal ascending aorta was
      cannulated and patients were systemically cooled. The cannula was advanced into
      the innominate artery and snared in place prior to opening and reconstructing the
      aorta with continuous LFCP. In all five patients, we completely avoided
      circulatory arrest and direct cannulation of the arch vessels. All patients
      survived and there were no adverse neurological outcomes.

PMID- 11343958
TI  - The use of absorbable material in correction of pectus deformities.
AB  - Various techniques have been described for correction of the congenital anterior
      chest wall deformities. We described a new technique in which 33 patients were
      used in correction of those deformities. In this new technique we used the
      resorbable copolymer plaque and polymer screw for the fixation of the sternum. We
      have obtained excellent results in one-year follow up period. This technique was
      developed to avoid a second operation, which usually requires for removal of the
      metal support. Resorption of copolymer plaques and polymer screws are completed
      at the end of the first year.

PMID- 11343959
TI  - Removal of migrating pectus bars by video-assisted thoracoscopy.
AB  - Surgical correction of pectus excavatum deformity with the use of a metal bar
      strut provides a good cosmetic result with a low complication rate. Reports of
      pectus bar migration are rare but we report three cases of bar migration which
      required thoracoscopic removal.

PMID- 11343960
TI  - Obstructing endobronchial malignant fibrous histiocytoma.
AB  - A 58-year-old male patient admitted with malignant fibrous histiocytoma of the
      left mainstem. Rareness and unusual presentation of malignant fibrous
      histiocytoma and surgical management for lung salvage made its reporting
      worthwhile. In this localization, prognostic characteristics are better than in
      the other localizations of lung and body.

PMID- 11343961
TI  - Colonic metastases from primary squamous cell carcinoma of the lung.
AB  - Lung cancer is the most common malignancy in the UK. Metastasis to the colon is
      very rare and only infrequently symptomatic. Here we report a case of squamous
      cell carcinoma of the lung which presented with symptoms from a colonic
      metastasis.

PMID- 11343962
TI  - Embolization of a ruptured intercostal artery aneurysm in type I
      neurofibromatosis.
AB  - We present the case of a female with history of a ruptured lumbar aneurysm years
      ago. She was known to have neurofibromatosis type I with the typical clinical
      signs. The patient was transferred to us with a hematothorax and an aortic lesion
      was suspected on the outside CT scan. Reevaluation of the investigation raised
      suspicion of a ruptured intercostal artery aneurysm, which was consequently
      demonstrated on angiography. The aneurysm was embolized and the patient recovered
      uneventful. We will discuss the optimal therapy for vessel lesions in
      neurofibromatosis type I.

PMID- 11343963
TI  - Intraluminal biopsy of a superior vena cava mass.
AB  - A number of methods have been devised for the biopsy of intracaval tumour masses
      but all risk damage to the cava and tumour dissemination. We report on a case in
      which the tumour mass was almost entirely within the superior vena cava and
      describe an 'endoscopic' technique for biopsy.

PMID- 11343964
TI  - Left cervical aortic arch associated with pseudocoarctation and aortic and mitral
      regurgitation: one-stage surgical repair.
AB  - Cervical aortic arch is rare with a prevalence of less than 1/10000 live births
      (Pediatr Cardiol 10 (1989) 205); but may occur with other cardiovascular
      congenital abnormalities. We report pseudocoarctation of a left-sided cervical
      aortic arch with an aberrant right subclavian artery and aortic and mitral
      regurgitation, corrected by an anterior mediastinal shunt from ascending to
      descending aorta and aortic and mitral valve replacements, as a one-stage
      procedure.

PMID- 11343965
TI  - Silver-coated prosthetic heart valve: a double-bladed weapon.
AB  - A St. Jude Medical Silzone was implanted in a 72-year-old female, suffering from
      mitral valve disease. Four months later, the patient had acute cardiac failure
      due to partial detachment of the prosthetic valve. The mitral annulus was
      ulcerated and there were multiple erosions in the myocardial tissue in contact
      with the prosthetic valve. Histological examination revealed chronic inflammation
      with hemosiderine deposits and giant cells. No allergy to silver ions was found.
      The silver-coated sewing cuff had caused a chronic inflammatory reaction due to a
      toxic reaction to silver. The Silzone valve was withdrawn from the market on
      January 2000.

PMID- 11343966
TI  - Sterol regulatory element-binding protein-1 as a dominant transcription factor
      for gene regulation of lipogenic enzymes in the liver.
AB  - Sterol regulatory element-binding proteins (SREBPs) are basic helix-loop-helix
      (bHLH) type transcription factors that control expression of genes involved in
      biosynthesis of cholesterol and fatty acids. Dietary studies with normal,
      transgenic, and knockout mice have established SREBP-1 as a dominant
      transcription factor regulating gene expression of lipogenic enzyme in the liver.
      Polyunsaturated fatty acids inhibit hepatic lipogenic enzymes through suppressing
      SREBP-1. Whereas SREBP-2 exerts sterol regulation through cleavage of the
      membrane-bound precursor protein to liberate the active nuclear form into the
      nucleus, SREBP-1 controls lipogenic enzymes by self-regulating its own
      transcription level. Promoter analysis of the SREBP-1 gene will be important to
      clarify the mechanism of nutritional regulation of lipogenic genes.

PMID- 11343967
TI  - Endoglin-deficient mice, a unique model to study hereditary hemorrhagic
      telangiectasia.
AB  - Hereditary hemorrhagic telangiectasia (HHT) is a genetic vascular disorder
      characterized by dilated vessels and arteriovenous malformations. Phenotypic
      heterogeneity, such as age of onset, severity of disease and organ involvement,
      is explained in part by two genes being mutated, endoglin (HHT1) and ALK-1
      (HHT2). Haploinsufficiency is the mechanism responsible for HHT. This implies
      that position and type of mutations cannot explain heterogeneity, because mutant
      proteins are not expressed at the cell surface and consequently cannot interfere
      with normal function. Based on this model, we generated mice expressing only one
      allele of endoglin, but in two different inbred strains, 129/Ola and C57BL/6.
      Phenotypic heterogeneity was also observed among the HHT mice and was very
      dependent on the genetic background. Our data strongly suggest that additional
      genes, contributed by the 129/Ola strain, are responsible for the vascular
      anomalies associated with HHT. The murine model is faithful to the human disease
      and should allow us to identify the modifier genes of HHT as well as to test
      potential therapeutic interventions.

PMID- 11343968
TI  - Activation of the platelet collagen receptor integrin alpha(2)beta(1): its
      mechanism and participation in the physiological functions of platelets.
AB  - When platelets are stimulated by agonists, integrin alpha(2)beta(1) (GP Ia/IIa),
      one of the platelet collagen receptors, is activated to forms with high
      affinities for its ligand collagen. Here we describe our studies to characterize
      the binding kinetics of the activated integrin forms and the activation
      mechanism. Under low agonist concentrations, integrin alpha(2)beta(1) is
      activated through a mechanism involving ADP/ADP receptors; and under high agonist
      concentrations, multiple signaling pathways are involved in its activation. Such
      differences in mechanism at low and high agonist concentrations are also
      suggested in the activation of integrin alpha(IIb)beta(3), the platelet
      fibrinogen receptor. We describe our flow adhesion studies, from which evidence
      was obtained about the involvement of integrin alpha(2)beta(1) activation in the
      physiological function of platelets, adhesion and thrombus formation.

PMID- 11343969
TI  - A genetic approach to detect muscle protein interactions in vivo.
AB  - An organism is required to identify biologically relevant protein interactions.
      We propose Drosophila and its indirect flight muscles as a suitable experimental
      system for genetic screenings for muscle protein interactions. The first attempt
      focused on troponin I (TnI) in view of the key role in thin filament regulation
      that this protein performs. Suppressors of a defined Tn I allele have been
      isolated as mutations in the heavy chain of myosin (MhC). This unsuspected
      functional interaction between TnI and MhC serves to illustrate one of the
      benefits of the approach. Four of the suppressors identified to date reside in
      the MhC head, around the actin-binding site and near the lips of the pocket where
      ATP is hydrolyzed. Two other suppressors correspond to a second site mutation in
      TnI and a mutation in the conserved region of Tropomyosin II (TmII),
      respectively. All the identified suppressors are mutations in constituents of the
      sarcomere, and most of them are structurally similar to human mutations causing
      familial hypertrophic cardiomyopathy (FHC). At least seven sarcomere proteins can
      lead to FHC and, consequently, the disease is heterogeneous and difficult to
      diagnose. In addition, putative natural suppressors may help obscure the origin
      of FHC. The genetic procedure, used here for muscle proteins, could help diagnose
      FHC and other myopathies, and extend to proteins of clinical interest in other
      tissues, including the nervous and circulatory systems.

PMID- 11343970
TI  - A novel role for STAT3 in cardiac remodeling.
AB  - The binding of ligands to gp130 activates the JAK/STAT signal transduction
      pathway, where STAT3 plays a central role in transmitting signals from the
      membrane to the nucleus. STAT3 is essential for gp130-mediated cardiac myocyte
      hypertrophy. Cardiac-specific disruption of gp130 was shown to present heart
      failure in response to mechanical stress accompanied by an increase in apoptosis.
      Thus, the inactivation of STAT3 resulting from the loss of gp130 may be a key
      event in the transition from cardiac hypertrophy to heart failure. Proper
      vascular growth is essential for normal cardiac development and remodeling
      process. Recently, bcl-xL and VEGF have identified as target genes of STAT and
      together can promote cardiac myocyte survival by prevention of apoptosis and
      restoration of energy deprivation. In this review, STAT3 is highlighted as a
      regulator of angiogenic factors, and activation of STAT-mediated signaling in the
      cardiac myocyte is proposed as a novel therapeutic strategy for the prevention of
      heart failure.

PMID- 11343971
TI  - Erbb4 and its isoforms: selective regulation of growth factor responses by
      naturally occurring receptor variants.
AB  - ErbB4 is a member of the epidermal growth factor receptor (EGFR, ErbB) family
      that mediates responses to neuregulins and other EGF-like growth factors. ErbB4
      is a central regulator of cardiovascular and neural development as well as
      differentiation of the mammary gland. A role for ErbB4 has also been implicated
      in malignancies and heart diseases. Four structurally and functionally distinct
      ErbB4 isoforms have recently been identified. One pair of isoforms differs within
      their extracellular juxtamembrane domains. These juxtamembrane ErbB4 isoforms are
      either susceptible or resistant to proteolytic processing that release a soluble
      receptor ectodomain. Another pair of ErbB4 isoforms differs within their
      cytoplasmic tails. Analysis of the intracellular signal transduction pathways
      indicates that both cytoplasmic ErbB4 isoforms can couple to the Shc-MAPK
      signaling pathway, while the other one is incapable of coupling to the
      phosphoinositide 3-kinase (PI3-K)-Akt pathway. The differences in the activation
      of signaling cascades are reflected in the cellular responses stimulated via the
      cytoplasmic isoforms. Both cytoplasmic ErbB4 isoforms can stimulate
      proliferation, but the isoform that cannot activate PI3-K is defective in
      stimulating cellular survival and chemotaxis. Together these four naturally
      occurring receptor variants provide a new level of diversity to the control of
      growth factor-stimulated cellular responses. Thus, the ErbB4 isoforms may have
      distinct and specific roles in the regulation of various developmental and
      pathological processes.

PMID- 11343972
TI  - Postulated role of inter-domain interaction within the ryanodine receptor in
      Ca(2+) channel regulation.
AB  - Key steps of excitation-contraction (E-C) coupling are (1) binding of the
      activator portion of the dihydropyridine (DHP) receptor (in skeletal muscle) or
      binding of the Ca(2+) entered through the DHP receptor (in cardiac muscle) to the
      ryanodine receptor (RyR), (2) a global protein conformational change of the RyR,
      and (3) opening of the RyR Ca(2+) channel, leading to muscle contraction. The
      conformational change (step 2) plays a major role in the Ca(2+) channel
      regulation, and a number of "regulatory domains" must be involved in this
      process. We postulate that the interaction among these regulatory domains is the
      central mechanism for the conformation-mediated control of the Ca(2+) channel. In
      this review, we summarize the recent data supporting this concept.

PMID- 11343973
TI  - Surface expression of Kv1 voltage-gated K+ channels is governed by a C-terminal
      motif.
AB  - The normal rhythmic beating of the heart relies on tight control of expression of
      voltage-gated ion channels in the plasma membrane of cardiac myocytes. Recently,
      a conserved motif was identified near the C-terminus of Kv1 voltage-gated K+
      channels that is required for efficient processing and surface expression.
      Furthermore, variations in the motif account for differences among normal
      channels in localization and the requirement for auxiliary subunits for robust
      expression. Thus, this motif is a key regulator of cell surface expression of Kv1
      family K+ channels.

PMID- 11343974
TI  - Bronchiolitis obliterans is not the primary cause of death in pediatric living
      donor lobar lung transplant recipients.
AB  - BACKGROUND: Obliterative bronchiolitis (OB) is the chief cause of mortality in
      cadaveric lung transplant patients (CL). But, is OB the primary cause of
      mortality for living donor lobar recipients? To answer this question, we reviewed
      the causes of mortality in our pediatric patients who underwent living donor
      lobar lung transplantation (LD) and compared them with our pediatric patients who
      received whole cadaveric lungs (CL). METHODS: Data collected included
      demographics, transplant type, hospital days, immunosuppression regimen, and
      cause of death. Statistical analysis was done using Fisher's Exact test and
      Student's t-test (mean +/- SD). RESULTS: From May 1993 to December 1999, 53
      patients underwent lung transplantation (21 males, 32 females; mean age 12.4 +/-
      5.4 years). Twenty-nine patients had LD procedures (12 males, 17 females; mean
      age 14.4 +/- 3.6 years) and 24 patients had CL surgery (9 males, 15 females; p =
      .78 [not significant]; mean age 9.8 +/- 6.3 years; p =.001). All patients
      received triple immunosuppression without induction. During the study period, 9
      LD (6 males, 3 females; mean age 15.7 +/- 5.0 years) and 14 CL (3 males, 11
      females; mean age 11.3 +/- 6.9 years) patients died. There was no significant
      difference between patients in the LD and CL groups who died with regard to
      gender (p = .08), age at the time of death (p = .12), mortality rate (p = .06),
      number of hospital days (p = .09), immunosuppressive medications (p > .08),
      incidence of non-specific graft failure (p = .26), or incidence of infection (p =
      .18). However, there was a significant difference in the incidence of OB between
      LD and CL recipients (p = .002). CONCLUSIONS: OB was not found to be the chief
      cause of mortality in pediatric LD recipients. We speculate that prevention of
      infections, possibly by a modest reduction in immunosuppressive therapy and
      aggressive antimicrobial therapy, may improve long-term survival in pediatric
      living donor lobar lung transplant recipients.

PMID- 11343975
TI  - Routine surveillance endomyocardial biopsy continues to detect significant
      rejection late after heart transplantation.
AB  - BACKGROUND: The need for continued surveillance endomyocardial biopsies beyond
      the first year after cardiac transplantation is controversial. We evaluated the
      incidence of rejections requiring treatment (International Society Heart and Lung
      Transplantation grade 3A or greater) in patients 5 years or more after heart
      transplantation. METHODS: We conducted a retrospective chart review of all
      patients who underwent at least 1 endomyocardial biopsy at our center 5 years or
      more after heart transplantation. RESULTS: A total of 461 biopsies were performed
      in 77 patients 5 or more years after heart transplantation. Nine episodes of
      grade 3A or greater rejection were identified in 8 of 77 patients (10%). During
      the first year, 7.6% of biopsies were grade 3A or greater. Grade 3A rejection
      occurred in approximately 3.5% to 4% of biopsies during years 2 to 7. The overall
      incidence of procedural related complications at our institution was < 0.5%.
      CONCLUSION: Endomyocardial biopsies continue to detect clinically significant
      rejection beyond 5 years after cardiac transplantation. The overall incidence of
      procedural related complications requiring treatment was low and none was life
      threatening. The absence of early rejection does not predict freedom from late
      rejection. Therefore, we continue to recommend surveillance biopsies in cardiac
      transplant recipients late after transplantation.

PMID- 11343976
TI  - Failure to down-regulate intragraft cytokine mRNA expression shortly after
      clinical heart transplantation is associated with high incidence of acute
      rejection.
AB  - BACKGROUND: Brain-death, ischemia and reperfusion damage have been implicated as
      initial factors that lead to a cascade of immunologic events that result in
      allograft rejection in experimental animals. Cytokines are thought to play a
      central role in this process. Therefore, we evaluated intragraft cytokine mRNA
      expression at an early stage after clinical heart transplantation and related
      these data to ischemia, immunosuppression, and rejection. METHODS: We sampled
      endomyocardial biopsies at 30 minutes (EMB 0) and at 1 week (EMB 1) after
      transplantation from 20 cardiac allograft recipients. Intragraft monocyte
      chemoattractant protein (MCP-1) and basic fibroblast growth factor (bFGF) mRNA
      expression levels were quantitatively measured using competitive template Reverse
      transcriptase polymerase chain reaction (RT-PCR). RESULTS: We measured
      significantly lower MCP-1 and bFGF mRNA expression levels in EMB 1 compared with
      EMB 0 (MCP-1, p = 0.006; bFGF, p = 0.019). We found no direct correlation between
      the cytokine mRNA expression levels in EMB 0 or EMB 1 and ischemic times,
      induction therapy, or cyclosporine whole-blood trough levels. Patients with a
      high incidence of acute rejection episodes (>2 in the first year) had higher bFGF
      mRNA expression levels (p = 0.009) and comparable MCP-1 mRNA expression levels (p
      = 0.378) at 1 week, compared with patients with a lower rejection incidence. The
      MCP-1 and bFGF mRNA expression levels in the first week were not associated with
      the development of graft vascular disease in the first year post-transplant.
      CONCLUSIONS: We found a significant decrease of intragraft MCP-1 and bFGF mRNA
      expression levels in the first post-operative week. Patients with a high
      incidence of acute rejection had higher bFGF mRNA expression levels in their
      first week biopsy. Therefore, we conclude that patients who fail to down-regulate
      their bFGF mRNA expression early after transplantation are at higher risk for
      acute rejection.

PMID- 11343977
TI  - Tacrolimus versus cyclosporine after lung transplantation: a prospective, open,
      randomized two-center trial comparing two different immunosuppressive protocols.
AB  - BACKGROUND: The need for better immunosuppressive protocols after lung
      transplantation led us to investigate tacrolimus (Tac) in combination with
      mycophenolate mofetil (MMF) and steroids or cyclosporine (CsA) in combination
      with MMF and steroids in a prospective, open, randomized trial after lung
      transplantation. METHODS: Between September 1997 and April 1999, 50 lung
      transplant recipients were randomized to receive either Tac (n = 26) or CsA (n =
      24) in combination with MMF and steroids. All patients underwent induction
      therapy with rabbit antithymocyte globulin (ATG) for 3 days. Freedom from acute
      rejection (AR), patient survival, infection episodes, and side effects were
      monitored. RESULTS: There was no difference in patient demographics between the
      two groups. Six-month and 1-year survival was similar (84.6% and 73.1% in the Tac
      group vs 83.3% and 79.2% in the CsA group). Freedom from AR at 6 months and 1
      year after lung transplantation was slightly higher in the Tac group (57.7% and
      50% vs 45.8% and 33.3%, p = not significant [n.s.]), whereas the number of
      treated rejection episodes per 100 patient days in the Tac group was
      significantly lower (0.225 vs 0.426, p < .05). Four patients in the CsA group had
      to be switched to Tac. Two patients in the CsA group had to be retransplanted.
      Incidence of infections was similar in both groups with a trend toward more
      fungal infections in the Tac group (n = 7 vs n = 1, p = n.s.). CONCLUSIONS: The
      combination of Tac and MMF seems to have slightly higher immunosuppressive
      potential compared with CsA and MMF. The effectiveness of Tac as a rescue agent
      is not paralleled with undue signs of overimmunosuppression.

PMID- 11343978
TI  - Listing for lung transplantation: life expectancy and transplant effect,
      stratified by type of end-stage lung disease, the Eurotransplant experience.
AB  - BACKGROUND: Increased referral for lung transplantation, persistent shortage of
      donor lungs, and moderate transplant outcome call not only for adequate listing
      criteria, but also for an optimal allocation scheme. We used global cohort
      survival after listing and survival benefit from transplantation to study the
      effect of a lung allocation scheme, primarily driven by waiting time, on the
      different types of end-stage lung disease. METHODS: We followed all adult
      patients consecutively listed for first, lung-only transplantation between 1990
      and 1996 (n = 1,208) for at least 2 years, with an additional 2-year follow-up
      after transplantation (n = 744). We used the competing risk method, the Kaplan
      Meier method, and a time-dependent non-proportional hazards model to analyze
      waiting-list outcome and global mortality after listing, post-transplant
      survival, and transplant effect, respectively. Each analysis was stratified for
      type of end-stage lung disease. RESULTS: At 2 years, 57% of the total cohort had
      received lung transplants, whereas 25% had died on the waiting list. The 2-year
      survival post-transplant was 55%. The global mortality of the cohort, since
      listing, amounted to 46% at 2 years. Compared with continued waiting, patients
      experienced benefit from transplantation by Day 100, which lasted until the end
      of the 2-year analysis period. We noticed the highest global mortality rates for
      patients with pulmonary fibrosis and pulmonary hypertension (54% and 52%);
      emphysema patients had the lowest (38%). Patients with pulmonary fibrosis and
      cystic fibrosis had much earlier benefit from transplantation, 55 and 90 days,
      respectively. Transplantation also benefited emphysema patients by Day 260.
      CONCLUSIONS: Lung transplantation conferred transplant benefit in a Western
      European cohort of adults, in particular for patients with pulmonary fibrosis and
      cystic fibrosis, but also for patients with emphysema. The global survival rate,
      reflecting the real life expectancy for a newly listed transplant candidate, is
      poor for patients with pulmonary fibrosis and pulmonary hypertension. Allocation
      algorithms that lessen the impact of waiting time and take into account the type
      of end-stage lung disease should be developed.

PMID- 11343979
TI  - Cardiac transplantation for cardiomyopathy and ischemic heart disease:
      differences in outcome up to 10 years.
AB  - BACKGROUND: Ischemic heart disease (IHD) and cardiomyopathy (CM) are the most
      common indications for heart transplantation. The aim of this study was to
      investigate the difference in clinical outcome between these two groups. METHODS:
      At our institution between 1987 and 1998 transplantation was performed in 133
      patients with IHD and 87 with CM. Follow-up was complete for all patients (mean
      87 months). RESULTS: Mean age at time of surgery was 51 +/- 5 years for IHD
      versus 39 +/- 9 years for CM recipients (p = 0.02). There was no difference in
      donor age, donor gender, or pre-operative hemodynamics between the two groups.
      The operative mortality was 11.2% in IHD recipients and 10.6% in CM recipients (p
      = 0.9). No differences were observed in intra-cardiac pressures or incidence of
      renal dysfunction, infection, or malignancy between the two groups. The incidence
      of peripheral vascular incidents was significantly higher for IHD recipients (13%
      vs 3%, p = 0.02). At 10 years, the incidence of coronary artery disease was 35%
      and 9%, respectively (p = 0.02). Mean NYHA status was 2.0 +/- 0.3 and 1.1 +/- 0.2
      for IHD and CM recipients, respectively (p = 0.013). The actuarial survival at 1,
      5, and 10 years was 77%, 62%, and 39% for IHD recipients compared with 85%, 82%,
      and 80% for CM recipients (p = 0.7, p < 0.0001 and p < 0.0001, respectively).
      CONCLUSION: After heart transplantation, medium- and long-term outcome is
      significantly better for CM than IHD recipients. In view of limited donor
      availability, it is appropriate to explore more vigorously alternative treatments
      for patients with severe ischemic left ventricular dysfunction.

PMID- 11343980
TI  - Comparative histopathology of endomyocardial biopsies in chagasic and non
      chagasic heart transplant recipients.
AB  - BACKGROUND: Heart transplantation has been an option for the treatment of
      chagasic (C) cardiomyopathy despite difficulties concerning the control of
      rejection and reactivation. The parasite-host interaction under the influence of
      immunosuppressive therapy may affect the immunological response to the graft in a
      pattern different from that in non-chagasic (NC) patients. The aim of this study
      was to compare the major histopathological features in heart transplantation in C
      and NC patients. METHODS: We studied 293 endomyocardial biopsies from two groups
      of heart transplanted patients, including 18 C and 15 NC. Both groups had
      identical surgical and clinical procedure except immunosuppressive therapy was
      lower in C patients. The histopathological parameters evaluated were the Quilty
      effect, rejection, C myocarditis reactivation, fibrosis, hypertrophy, and
      ischemia. In addition, lymphocytic cellular infiltration of myocarditis due to
      rejection or reactivation was immunophenotyped in the biopsies of both groups
      with rejection grades 3 to 4, in biopsies with signs of reactivation, and in
      fragments of the receptor heart with chronic C myocarditis. A search for
      Trypanosoma cruzi was performed in all biopsies in the C group in which
      lymphocyte immunophenotyping was done. We used immunofluorescence and confocal
      microscopy. RESULTS: The Quilty effect was present in 23% of the biopsies,
      involving 69.7% of the patients without a significant difference between groups
      (p = 0.509). Rejection was frequently observed in biopsies with the Quilty effect
      and the effect often recurred in the same patient. Rejection grades 3 to 4 was
      more frequent in the C group (p = 0.023). There were 5 episodes of Chagas'
      disease reactivation with myocarditis in 2 cases. The mean numbers of CD8+ and
      CD4+ T cells, and the CD4+-to-CD8+ ratio were similar for rejection in both
      groups (p > 0.05), while the CD4+-to-CD8+ ratio was significantly lower in
      chronic C myocarditis compared to rejection in the C group (p = 0.043). There was
      no significant difference in ischemic damage or interstitial fibrosis in the
      groups but there was a higher frequency of hypertrophy in the NC group (p =
      0.007). CONCLUSIONS: The histopathological features of heart transplantation in C
      patients did not differ from that in NC patients in regard to the Quilty effect,
      development of myocardial fibrosis and ischemia. However, the higher involvement
      of the C group for rejection grades 3 to 4 suggested higher susceptibility to
      this event. The similarity of the lymphocytic cellular composition for rejection
      in both groups indicates that C patients respond to immunological stimulus in a
      similar pattern as NC patients.

PMID- 11343981
TI  - When withdrawal of life-sustaining care does more than allow death to take its
      course: the dilemma of left ventricular assist devices.
AB  - BACKGROUND: Left ventricular assist devices (LVADs) are a relatively new
      technology that is increasingly used to preserve cardiac function. These devices
      work by a mechanism that may complicate ethical decision-making for patients who
      subsequently lose decision-making capacity and are no longer considered
      transplant candidates. METHODS: Using a clinical case from our medical center, we
      explored the complex ethical issues associated with the discontinuation of LVAD
      therapy by discussing how this device is distinct from the withdrawal of other
      treatments. RESULTS: While halting an implanted LVAD may permit a patient to die,
      the deactivated device itself may contribute to patient death due to the
      potential for blood backflow and pooling, as well as the disruption of heart
      contractility. Inadequate informed consent and failure to appoint a surrogate
      decision-maker in advance of the implant procedure resulted in a complex ethical
      dilemma for the patient's family and the medical team. CONCLUSIONS: Clinicians
      and families must consider the benefits and burdens of LVAD therapy as they do
      when considering removal of other life-sustaining treatment. The informed consent
      process associated with LVADs as bridging technology should include extensive
      consideration of the purpose of the device, future circumstances in which it may
      be halted, and how such situations would be recognized and handled. Appointment
      of a surrogate decision-maker before the surgical procedure is essential.

PMID- 11343982
TI  - Improved preservation of coronary endothelial function with Celsior compared with
      blood and crystalloid solutions in heart transplantation.
AB  - BACKGROUND: Endothelial injury from preservation solutions has been implicated in
      acute coronary vasospasm and pathologic activation of the endothelium, which can
      contribute to the development of graft coronary vasculopathy after heart
      transplantation. Preservation solutions with a powerful antioxidant capacity may
      decrease the occurrence of these complications. MATERIALS AND METHODS: This study
      was designed to evaluate the effect of Celsior (an anti-oxidant solution
      specifically designed for cardiac preservation) in a model of heart preservation
      (4 hours at 4 degrees C to reproduce the situation encountered in clinical heart
      transplantation) compared two commonly used cardioplegic and preservation
      strategies on coronary endothelial function. Endothelium-dependent relaxation of
      normal porcine epicardial coronary arteries to serotonin (5-HT, an agonist that
      activates 5-HT(1d) receptors coupled to Gi proteins) and bradykinin (BK, which
      activates B2 receptors coupled to Gq proteins) was studied in standard organ
      chamber experiments in the following groups: a control group was submitted to
      immediate excision without cardioplegia and preserved in saline solution (0.9%
      NaCl) for 4 hours (Group 1); two groups had cardioplegia induced with a
      crystalloid solution and were stored for 4 hours in saline (Group 2) or 4 hours
      in Celsior solution (Group 3); and two groups had cardioplegia induced with
      normothermic blood cardioplegia and were stored for 4 hours in the saline (Group
      4), or 4 hours in Celsior solution (Group 5). Finally, two groups underwent
      cardioplegia with Celsior and were stored for 4 hours in saline (Group 6), or 4
      hours in the Celsior solution (Group 7). All cardioplegia solutions were at 4
      degrees C (except blood cardioplegia at 37 degrees C) and all preservations
      solutions were at 4 degrees C. RESULTS: Endothelium-dependent relaxations to
      serotonin were significantly decreased in all groups except the Celsior + Celsior
      group compared with the control group. There were no significant differences in
      relaxation to bradykinin except in one group. Use of the Celsior solution for
      induction of cardioplegia and storage better preserved endothelium-dependent G
      protein-mediated relaxation compared with the other arrest and preservation
      strategies. CONCLUSIONS: The observed effect may be associated with an
      improvement in both short- and long-term outcome in heart transplantation,
      especially because these alterations may be further compounded by reperfusion.

PMID- 11343983
TI  - L-Arginine in lung graft preservation and reperfusion.
AB  - BACKGROUND: Inhaled nitric oxide has been shown to ameliorate early lung graft
      dysfunction. It improves oxygenation by inducing pulmonary vasodilatation in well
      ventilated lung areas, and it also modulates leukocyte-endothelium interactions.
      We used a porcine, single lung transplantation model to evaluate whether the
      benefits of exogenously administered gas could be achieved easier by adding L
      arginine, the substrate of endogenous nitric oxide synthesis, as an additive to
      the flush solution and intravenously during reperfusion. METHODS: Six pig lungs
      were flushed with modified Euro-Collins solutions containing L-arginine (2
      g/liter). After cold (4 degrees C) storage, the left lung was transplanted.
      Ischemic time was 260 minutes. The recipients received intravenous boluses of L
      arginine (30 mg/kg), followed by infusion (20 mg/kg/min) during the first 30
      minutes of reperfusion. Six control animals received saline as placebo. We
      measured the blood flow and pulmonary vascular resistance (PVR) in the
      transplanted and in the native lung using a right heart bypass model. We measured
      blood gases, leukocyte counts, plasma free-radical trapping capacity, and diene
      conjugates in pulmonary venous blood and myeloperoxidase activity of the lung
      tissue. RESULTS: Pulmonary vascular resistance was 4 to 5-fold higher in the
      transplanted lung than in the native lung, which received 80% of the total blood
      flow. L-arginine reduced PVR by 30% in the native lung (p < 0.001), but not in
      the transplanted lung. L-arginine had no effect on oxygenation or carbon dioxide
      exchange of the transplanted lung. Nor did L-arginine treatment have any effect
      on leukocyte sequestration or myeloperoxidase activity in the transplanted lung.
      The plasma antioxidant capacity in venous blood of the transplanted lung almost
      doubled shortly during early reperfusion without influence of L-arginine.
      CONCLUSIONS: L-arginine reduced PVR in the native lung but did not improve
      pulmonary hemodynamics, gas exchange, or reduce leukocyte sequestration of the
      transplanted lung.

PMID- 11343984
TI  - FR167653 attenuates ischemia and reperfusion injury of the rat lung with
      suppressing p38 mitogen-activated protein kinase.
AB  - BACKGROUND: FR167653 is a potent suppressant of tumor necrosis factor (TNF)-alpha
      and interleukin-1 (IL-1) production, and was shown to attenuate ischemia and
      reperfusion (I/R) organ injury in our previous experiment. Because p38 mitogen
      activated protein (MAP) kinase has been reported to regulate the production of
      TNF-alpha and IL-1, we examined the effects of FR167653 in the rat lung I/R model
      and determined the expression and activation of p38 MAP kinase. METHODS:
      Experiment 1: After 1 hour of ischemia, p38 MAP kinase, phosphorylated p38 MAP
      kinase (active form), histologic changes of the lung, and serum levels of TNF
      alpha and IL-1beta were examined. Experiment 2: After 2 hours of reperfusion,
      arterial oxygen content (PaO(2)) and saturation (SaO(2)), serum TNF-alpha and IL
      1beta levels, and histologic changes in the lung were examined. Rats were divided
      into three groups in Experiment 1. In the control group, a saline solution was
      administered and, in the FR group, 0.1 mg/kg per hour of FR167653 was
      administered, intravenously throughout the experiment, beginning 30 minutes
      before ischemia. In the non-ischemic group, samples were taken soon after
      thoracotomy. The rats were divided into control and FR groups in Experiment 2.
      RESULTS: Experiment 1: One hour of ischemia induced almost no changes in the lung
      or serum cytokine levels. Meanwhile, FR167653 markedly attenuated the expression
      of phosphorylated p38 MAP kinase. Experiment 2: SaO(2) and PaO(2) were improved,
      serum cytokines were lower, and lung damage was less extensive in the FR group
      than in the control group. CONCLUSION: FR167653 attenuates I/R injury of the lung
      and this attenuation is associated with suppression of p38 MAP kinase activation.

PMID- 11343985
TI  - Simultaneous study of metabolism and function following cardioplegic arrest: a
      novel method of evaluation of the transplanted heart in the rat.
AB  - BACKGROUND: Limitations of the isolated perfused rat heart model for heart
      preservation studies include short study time due to the lack of stability of the
      preparation. We aimed to develop a new experimental model based on heterotopic
      heart transplantation in the rat to achieve simultaneous (31)P magnetic resonance
      spectroscopy (MRS) and functional study of the transplanted heart during early
      and late blood reperfusion. METHODS: Twenty-five Lewis rats underwent heterotopic
      abdominal isograft heart transplantation and were randomized in two groups.
      Hearts were harvested after cardioplegic arrest induced with Centre de Resonance
      Magnetique Biologique et Medicale (CRMBM) solution and then stored at 4 degrees C
      for a total ischemic time of 3 hours. Graft contractility measurement and
      simultaneous (31)P MRS were performed after 1 hour and 24 hours of blood
      reperfusion, respectively, in groups I (n = 12) and II (n =13). RESULTS:
      Contractility improved during reperfusion. The mean rate pressure product plus or
      minus standard error of mean increased from 11,373 +/- 1,377 mm Hg/min in group I
      to 24,363 +/- 3,860 mm Hg/min in group II (P = 0.003), while mean dP/dtmax
      increased from 1,642 +/- 173 mm Hg/sec to 2,571 +/- 333 mm Hg/sec, respectively
      (p = 0.03). Simultaneously, both the phosphocreatine/adenosine triphosphate (ATP)
      and inorganic phosphate/ATP ratios decreased from group I to group II (p = 0.025
      and p = 0.015, respectively), suggesting regeneration of the intracellular pool
      of ATP in group II. CONCLUSIONS: Simultaneous functional and metabolic studies of
      the transplanted heart are feasible in rats. Improvement in contractility during
      late reperfusion is contemporary with significant changes in energetic
      metabolism. Our model should be useful for the further improvement of heart
      preservation, which may result in significant clinical progress.

PMID- 11343986
TI  - Prolonged survival of rat cardiac allograft with proinflammatory cytokine
      inhibitor.
AB  - BACKGROUND: Proinflammatory cytokines, such as tumor necrosis factor (TNF-alpha)
      and interleukin-1 (IL-1), play important roles in acute allograft rejection.
      FR167653 is an inhibitor of these cytokines that acts through inhibition of the
      mitogen-activated protein kinase p38 pathway. We examined the effect of FR167653
      on allograft rejection. METHODS: We used Brown-Norway and Lewis rats as donors
      and recipients, respectively. We performed heterotopic cardiac transplantation.
      The control group consisted of untreated rats. In the experimental groups,
      recipients were intraperitoneally injected with FR167653 just after operation,
      followed by daily injection of the drug from Day 1 to 10. We divided 20 rats into
      5 groups, which received varying doses of FR167653, ranging from 75 to 300
      mg/kg/day. RESULTS: In the control group, the mean graft survival was 6.8 +/- 0.3
      days. FR167653 at 150 mg/kg/day significantly prolonged the survival period (up
      to 12.1 +/- 1.5 days, p = 0.002). Histologically, FR167653 markedly suppressed
      cellular infiltration on Day 5 post-transplantation. The serum level of TNF-alpha
      in the control group was persistently elevated from 9.3 +/- 3.9 pg/ml to 11.3 +/-
      3.8 pg/ml, whereas FR167653 significantly suppressed the level to <1.4 +/- 1.4
      pg/ml. CONCLUSIONS: FR167653 prolonged rat cardiac allograft survival by
      suppressing the action of proinflammatory cytokines.

PMID- 11343987
TI  - Early growth-response factor 1 and basic transcriptional element-binding protein
      2 expression in cardiac allografts.
AB  - Early growth-response factor 1 (Egr-1) and basic transcriptional element-binding
      protein 2 (BTEB2) are transcriptional factors that regulate multiple genes
      involved in phenotypic changes of smooth muscle cells (SMCs), one of the
      outstanding pathologic features of chronic cardiac allograft rejection. In this
      study, we used a heterotopic abdominal heart transplant model in monkeys to
      evaluate the roles of these molecules in graft coronary vasculopathy. We
      demonstrated that Egr-1 and BTEB2 are induced in vascular SMCs of rejected
      cardiac allografts well before morphologic changes, such as intimal thickening.
      These findings suggest that expression of Egr-1 and BTEB2 is one of the initial
      events in allograft angiopathy.

PMID- 11343988
TI  - Outcome of heart transplantation in patients previously infected with hepatitis C
      virus.
AB  - The lack of knowledge about the course of hepatitis C virus infection (HCV)
      before heart transplantation (HTx) prompted us to describe our experience with 4
      such patients who presented with positive HCV serology before surgery. Two
      experienced non-liver related deaths at 3.5 and 5 years after HTx, and none of
      the patients developed signs of hepatic insufficiency during the follow-up (mean
      3.8 years). Tests for HCV antibodies were frequently negative, whereas viral RNA
      was detected in 81% of the measurements, showing that virus detection techniques
      seem to be more sensitive than serology techniques in detecting HCV infection in
      this group of patients. Although immunosuppression promotes active HCV
      replication, it does not seem to change the chronic features of HCV infection
      during the first years in patients with good liver function.

PMID- 11343989
TI  - Development of atherosclerotic plaque with endothelial disruption in Watanabe
      heritable hyperlipidemic rabbit aortas.
AB  - To better understand the morphogenesis of atherosclerotic plaque, we evaluated
      temporal distribution of leukocytes, macrophages, foam cells, vascular smooth
      muscle cells, and subendothelial lipid in Watanabe heritable hyperlipedimic
      (WHHL) rabbit aortas. Aortas of WHHL (n=20) and New Zealand White (NZW, controls;
      n=8) rabbits were perfusion fixed at 1, 3, 6, and 12 months of age. At initial
      gross evaluation of lipid distribution, we identified aortic areas at high risk
      for lesion development. In WHHL rabbits, the lipid-positive portion of high-risk
      areas increased from 3% at 1 month to 50% at 12 months; during the same period,
      adherent cell count increased from <1 leukocyte and monocyte/mm(2) to 25
      leukocytes, 44 monocytes, and 10 foam cells/mm(2). Controls showed no increase
      over time in lipid-positive areas or cellular adherence to the endothelium. One
      month-old WHHL rabbit aortas had scattered lipid-positive cells in the intima
      (primarily branch points). Immunostaining of these areas did not show rabbit
      macrophages (RAM antibody) but were actin positive. Occasionally, platelets and
      monocytes adhered to the endothelial surface. By age 3 months, well-defined fatty
      streaks/atherosclerotic plaques had RAM-positive cells within foam cell core,
      along core margins, and in focal clusters in the fibrous cap and subendothelium.
      By age 12 months, isolated RAM-positive cells were on the endothelial surface,
      and surface morphology showed endothelial cell disruption foci containing
      clusters of macrophages and foam cells. Our results indicate that lipid
      accumulation (extra- and intracellular) is important in the early development of
      atherosclerotic lesions; a corresponding, slower accumulation of adherent cells
      on the lesion surface promotes lipid conversion from fatty streak to plaque.

PMID- 11343991
TI  - Histological remodeling in an ovine heart failure model resembles human ischemic
      cardiomyopathy.
AB  - Staged coronary embolization, causing myocardial microinfarctions, has been shown
      in dogs and sheep to cause chronic ischemic heart failure (HF) that resembles the
      hemodynamics of the human condition. However, its histopathological basis remains
      unclear. We examined the hypothesis that the ventricular remodeling seen in such
      sheep resembles the histopathology of human ischemic cardiomyopathy (ICM).
      Understanding the pathophysiology of this model will determine its place in the
      development of treatment strategies for HF. Global left ventricular (LV) damage
      resulting in HF was induced by staged coronary embolization in 11 sheep. Six
      others served as controls (normal control, NC). In HF sheep, the heart was
      harvested 6 months after LV ejection fraction (EF) had stabilized at <35%.
      Histopathological profiles were compared in biventricular transverse sections at
      midpapillary level using computed image analysis. LV end-diastolic volume
      increased in the HF group from 84.9+/-29 to 122.4+/-30.3 ml (n=11, P<.05), but
      myocytes across the LV wall in noninfarcted zones decreased (435.7+/-38.2 NC;
      297.8+/-48.4/unit area HF; n=11, P<.0001) as did myocyte nuclear density (990.5+/
      51.5 NC; 677.5+/-121.1/mm(2) HF, n=11, P<.0001). In contrast, LV replacement and
      interstitial fibrosis increased as did myocyte diameter in noninfarcted zones:
      0.1+/-0.1 to 6.2+/-4.5% (P=.0049); 2.0+/-1.0 to 7.6+/-4.9% (P=.0149); and 10.0+/
      0.5 to 15.9+/-2.2 microm (P<.0001), respectively. Although LV myocyte nuclear
      length increased (10.2+/-1.0 NC; 12.2+/-0.9 microm HF, n=11, P=.0006), right
      ventricular (RV) myocyte nuclear density and length did not alter. In this ovine
      chronic HF model, LV dilation and interstitial and myocyte remodeling resemble
      human ICM.

PMID- 11343990
TI  - Pretreatment with the gap junction uncoupler heptanol does not limit infarct size
      in rabbit heart.
AB  - Previous findings indicate that heptanol, an agent well-recognized to disrupt
      chemical signaling between myocytes by uncoupling of gap junctions, significantly
      limited infarct size when administered at the time of reperfusion. Our aim was to
      assess on the potential role of cell--cell communication via gap junctions during
      ischemia by investigating whether "loading" the soon-to-be ischemic territory
      with heptanol would limit myocardial necrosis. Five isolated buffer-perfused
      rabbit hearts were pretreated with heptanol (0.5 mM) for 10 min, while 12 served
      as controls. In the final 30 s of treatment, a large marginal branch of the left
      circumflex coronary artery was occluded for 30 min followed by 2 h of
      reperfusion, and infarct size was delineated by tetrazolium staining. Heptanol
      had no significant effect on the extent of infarct: area of necrosis (AN,
      expressed as a percentage of the myocardium at risk) was 75+/-3% and 72+/-8% in
      vehicle- and heptanol-treated groups (P=.76). Thus, our results suggest that cell
      to-cell communication via gap junctions during coronary artery occlusion does not
      contribute importantly to the development of necrosis in rabbit heart.

PMID- 11343992
TI  - Nitric oxide synthase expression in lungs of pulmonary hypertensive patients with
      heart disease.
AB  - Since little is known about the contribution of endothelial nitric oxide synthase
      (e-NOS) to the mechanism of pulmonary vasospasm and the development of pulmonary
      vascular occlusive disease, we elucidate how e-NOS is expressed in lung biopsy
      specimens obtained from operative patients with pulmonary hypertension. Lung
      biopsy specimens were obtained from 17 patients who underwent open-heart
      operations for various heart diseases. A piece of normal lung specimen was also
      obtained from the resected lungs of three lung cancer patients as a control. e
      NOS expression was visualized with a monoclonal antibody against e-NOS, and the
      level of expression was partially quantified. Significantly high levels of e-NOS
      expression were seen in adult patients, whose preoperative mean pulmonary
      arterial pressures were greater than 20 mm Hg. In contrast, e-NOS expression in
      pediatric patients with the same levels of mean pulmonary arterial pressure was
      the same as that in the controls and in low pulmonary arterial pressure. There
      was a statistically significant positive correlation between the level of e-NOS
      expression and Heath--Edwards grading. These data suggest that the e-NOS
      expression in lung tissue is induced when pulmonary vascular obstructive diseases
      progress.

PMID- 11343993
TI  - Pathology of the diffuse variant of supravalvar aortic stenosis.
AB  - Supravalvar aortic stenosis is a rare congenital heart anomaly, producing left
      ventricular outflow tract obstruction. Of the two anatomic variants that have
      been described, diffuse type is the rarest. We report five such cases in children
      between two months and nine years of age. None had features of Williams syndrome.
      The entire aorta was involved in three cases, with abdominal aortic coarctation
      in two cases. Stenosis was mainly due to involvement of the media, which showed
      smooth muscle hypertrophy, abnormal elastic fibers, and mild collagenization.
      Predominant intimal change was seen in one case. Pulmonary, coronary, arch,
      renal, and common iliac arteries were also involved.

PMID- 11343994
TI  - Morphological changes in atrial appendages removed during the maze procedure: a
      comparison with autopsy controls.
AB  - Atrial fibrillation (AF) is commonly encountered in clinical practice and
      typically it is treated with pharmacological agents. Some patients whose
      arrhythmias are resistant to pharmacological therapy undergo the maze procedure,
      which is a surgical treatment. The atrial appendages are removed as part of the
      surgical procedure. These appendages often demonstrate mycocyte hypertrophy,
      vacuolar degeneration and other changes that may be seen in cardiomyopathies. We
      examined 19 of these appendages and compared them with 17 autopsy controls, 12 of
      whom had documented coronary atherosclerotic disease and 5 of whom did not. We
      semiquantitatively measured the amount of vacuolar degeneration, interstitial
      fibrosis, myocyte hypertrophy and intramyocardial adipose tissue. Univariate and
      multivariate analysis was performed and revealed that vacuolar degeneration were
      significantly more common in appendages of patients with arrhythmias than the
      autopsy controls (P<.0004). The other three histological features studied were
      not significantly different in the three groups. Ultrastructural studies on
      atrial tissue excised during the maze procedure, retrieved from the paraffin
      blocks, revealed degenerative changes similar to cardiomyopathic myocardial
      tissue. Vacuolar degeneration is commonly seen in atrial appendages removed in
      patients with chronic AF. Myocyte hypertrophy is a nonspecific finding and may
      occur in patients with arrhthymias and coronary artery disease.

PMID- 11343995
TI  - Arrhythmic sudden cardiac death in a 3-year-old child with intimal fibroplasia of
      coronary arteries, aorta, and its branches.
AB  - We report an unusual case of "arrhythmic" sudden cardiac death in a 3-year-old
      child who died of ischemic myocardial lesions as a result of intimal fibroplasia
      of the coronary arteries. Also affected were the aorta and its major branches,
      whereas renal and mesenteric arteries, celiac trunk, and systemic veins were
      normal. Histopathologic examination showed severe concentric thickening of intima
      because of a proliferation of spindle-shaped cells (mesenchymal cells) set in an
      abundant extracellular matrix. In some vascular segments the intima was densely
      fibrotic and hyalinized. No significant inflammation, foam cells, cholesterol
      clefts, or other evidence of atheroma were present. The intimal lesions did not
      involve the media and/or the adventitia. Immunohistochemical staining of intima
      showed the proliferating mesenchimal cells to be myofibroblastic. Reactions for
      vimentin and smooth muscle actin were positive, while those for desmin, myosin,
      CD34, and Factor VIII were negative.

PMID- 11343996
TI  - Trans-urethral whole layer core biopsy for detection of residual tumor after
      neoadjuvant therapy in invasive bladder cancer.
AB  - The most essential information necessary for the treatment of bladder cancer is
      to know its exact staging. We have developed a percutaneous whole layer core
      biopsy (PC-WLCB) of the bladder tumor and applied it successfully since April
      1985 for the staging and evaluation of neoadjuvant therapy in locally invasive
      bladder cancer. We report here a modified method, the trans-urethral WLCB (TU
      WLCB) and present its clinical results. Methods: A 20 F. rigid nephroscope was
      introduced trans-urethrally and an 18 gauge, 350mm-long biopsy needle or newly
      developed 450mm-long biopsy needle was advanced to the tumor through the
      nephroscope. Biopsy was performed under trans-abdominal ultrasound guidance.
      Results: Specimens of all 20 TU-WLCB cases included the muscle layer and adipose
      tissue, and demonstrated small focus of residual cancers after neoadjuvant
      therapy. Serious complications were not observed so far. Conclusion: TU-WLCB may
      prove to be a reliable method to stage and evaluate neoadjuvant therapy for
      invasive bladder cancer.

PMID- 11343997
TI  - Extended sector biopsy for detection of carcinoma of the prostate.
AB  - Purpose: To determine whether an extended sector biopsy of the prostate will
      increase the detection of prostate cancer, without causing an increase in
      morbidity. Materials and Methods: A total of 74 men with a mean age of 62.3 years
      (46-98 years) who either had an elevated PSA or an abnormal digital rectal exam
      underwent a transrectal ultrasound guided needle biopsy. Beginning on 7/1/98, an
      extended sector biopsy technique was performed on 74 patients by one urologist
      (RRB). Each transrectal ultrasound guided needle biopsy included 12 total cores
      (normal sextant biopsy, 2 in each peripheral zone, and 2 in the transition zone).
      We retrospectively reviewed the biopsy results for the location of cancer. PSA
      data and morbidity of the procedures were reviewed. Results: Of 74 total
      patients, 40 (54.1%) were positive for adenocarcinoma of the prostate. There were
      10 positive results detected only in the additional zones. If one looks at the
      total number of cancers detected (40), then 10/40 (25%) of the cancers detected
      were found in the additional regions only or in 13.5% of all patients biopsied.
      Of the 10 patients with sector only prostate cancer, 8 were detected in the
      peripheral zone, 1 in the transition zone and 1 in both zones. All 10 patients
      had a Gleason pattern score 3+3=6 or 4+3=7. There were no atypical or PIN cores
      found in the sector zones only. PSA ranged from 1.2-142 (median 6.0 ng/ml). The
      median PSA was 6.2 ng/ml in all patients found to have cancer, and 6.0 ng/ml in
      the cancers detected only in the additional zones. There was 1 (1.4%)
      complication of urinary retention and fever. Conclusion: Our study suggests that
      an extensive sector biopsy may increase the detection of prostate cancer by 13.5%
      over a routine sextant biopsy, without demonstrable serious morbidity.

PMID- 11343998
TI  - Non-invasive bladder cancer presenting with renal failure.
AB  - Obstructive uropathy in a patient with carcinoma of the bladder is usually
      considered to be a sign of advanced disease. We discuss a patient who presented
      with obstructive uropathy as a sequelae of large volume yet superficial and organ
      confined bladder cancer.

PMID- 11343999
TI  - Efficacy of a synthetic lytic peptide in the treatment of prostate cancer.
AB  - In the last several years, significant effort has been applied to identifying
      novel agents with effectiveness against prostate cancer. These studies were
      designed to determine the efficacy of one of these novel compounds, D2A21, in the
      treatment of an animal model of prostate cancer. Using the Mat-Ly-Lu(MLL) line of
      the Dunning R-3327 rat prostate adenocarcinoma model, the optimal dose, schedule
      and route of administration of D2A21 were established. A study involving the G
      line was used to further support these findings. In addition, hemotoxylin and
      eosin stained tissue samples were examined to investigate the extent of
      inhibition of lung metastases in animals injected with MLL cells. When D2A21 was
      injected intraperitoneally or subcutaneously, MLL and G cell tumor growth was
      inhibited 50-72% as demonstrated by both tumor volumes and weights. The optimal
      dosage of 0.179 mg/injection was established and it was determined to be most
      efficacious when administered five times per week. At this concentration, D2A21
      appears to have no significant toxicity. Additionally, D2A21 increased the
      survival rate from only 25% to 70-75% in animals that were challenged with a
      large number of tumor cells. The peptide D2A21 is able to significantly inhibit
      tumor growth in rat models of prostate cancer. In addition, it can inhibit
      metastases and decrease deaths resulting from metastases in these animals.

PMID- 11344000
TI  - Mutations within the tumour suppressor gene p53 are not confined to a late event
      in prostate cancer progression. a review of the evidence.
AB  - Mutations in the p53 tumour suppressor gene are generally believed to be a late
      event in the progression of prostate cancer, and are associated with androgen
      independence, metastasis, and a worse prognosis. In this review, we examine the
      current literature available on p53 mutations and focus on stages A (T1) and B
      (T2) of prostate cancer. We report here that p53 mutations can be found in
      approximately one third of prostate cancers that are clinically localized to the
      prostate. In addition, high levels of p53 mutation are found in normal prostate
      tissue of prostate cancer patients, prostatic intraepithelial neoplasia, and
      benign prostatic hyperplasia. The limitations of techniques used to determine p53
      mutations are discussed, as well as other modes of p53 loss in early stage
      prostate cancer.

PMID- 11344001
TI  - Randomized phase 2 trial of ketoconazole and ketoconazole/doxorubicin in androgen
      independent prostate cancer.
AB  - Eighty-nine patients with progressive prostate cancer despite suppression of
      testosterone and withdrawal of anti-androgens were studied. This was a relatively
      advanced population, with 63 of 89 having either osseous metastases (mets) beyond
      the axial skeleton or visceral mets. Patients were randomly assigned to receive
      either ketoconazole alone, or ketoconazole with weekly doxorubicin. All patients
      received replacement hydrocortisone. The primary endpoints were response and
      survival. Based on PSA reduction criteria (>/= 80% maintained for at least 8
      weeks), 14 of 45 patients (31%) in the single-agent ketoconazole arm responded.
      Sixteen of 44 patients (36%) in the combination ketoconazole/doxorubicin arm
      responded. There were no important differences between the two treatments in any
      outcome measure. The median overall survival for all patients was 12.5 months;
      median time to progression was 3.3 months. Toxicity was significant with both
      regimens, and more severe in the doxorubicin arm. Fully 20% of patients in each
      arm discontinued therapy due to intolerable side effects.Each of these regimens
      is toxic, and produced responses in fewer than half of treated patients. Although
      the observed median survival does compare favorably with reports from similar
      cohorts treated in the community, the potential benefit is only modest. In our
      view, neither of these regimens is sufficiently promising to justify phase 3
      evaluation.

PMID- 11344002
TI  - The application and technology of implantable neuromuscular stimulators: an
      introduction and overview.
AB  - The design of an implantable neuromuscular stimulator represents a trade-off in
      which the desire to maximise functionality and operational life competes with the
      need for the implanted device to be small, reliable, safe, and easy to use. In
      this introduction and overview we consider the basic problems and the different
      approaches to their solution.

PMID- 11344003
TI  - BION system for distributed neural prosthetic interfaces.
AB  - We have developed the first in a planned series of neural prosthetic interfaces
      that allow multichannel systems to be assembled from single-channel micromodules
      called BIONs (BIOnic Neurons). Multiple BION implants can be injected directly
      into the sites requiring stimulating or sensing channels, where they receive
      power and digital commands by inductive coupling to an externally generated radio
      frequency magnetic field. This article describes some of the novel technology
      required to achieve the required microminiaturization, hermeticity, power
      efficiency and clinical performance. The BION1 implants are now being used to
      electrically exercise paralyzed and weak muscles to prevent or reverse disuse
      atrophy. This modular, wireless approach to interfacing with the peripheral
      nervous system should facilitate the development of progressively more complex
      systems required to address a growing range of clinical applications, leading
      ultimately to synthesizing complete voluntary functions such as reach and grasp.

PMID- 11344004
TI  - Implanted stimulators for restoration of function in spinal cord injury.
AB  - Neuroprostheses that electrically stimulate paralyzed muscles provide functional
      enhancements for individuals with spinal cord injury and stroke such as standing
      and stepping, reaching and grasping, and bladder and bowel function. For chronic
      applications, implanted neuroprostheses lead to reliable, low-maintenance and
      patient-acceptable systems. The advantages of such systems are discussed followed
      by a generic description of implantable stimulators. Features of current first
      and second generation neuroprostheses developed at our centre are discussed
      followed by our experience in the application of these devices in the
      rehabilitation of individuals with spinal cord injury.

PMID- 11344005
TI  - An implant for chronic selective stimulation of nerves.
AB  - An implantable stimulator system has been developed for nerve stimulation. The
      system is capable of stimulating selectively, either by fibre position, fibre
      size or by sending action potentials in one direction only, based on the use of
      nerve cuffs. The stimulator produces either quasi-trapezoidal current pulses, to
      allow anodal blocking, or conventional rectangular-shaped current pulses, of
      amplitude 20 microA to 5 mA (in 20 microA steps) with duration of 16 micros to 1
      ms (in 8 micros steps). For safety, both active and passive charge balancing is
      used. The amplitude of the active charge-balancing phase can be varied between
      1/7 and 1/47 of the pulse amplitude. During manufacture, each implant is
      customised so as to drive either 6 quasi-tripolar (dipolar), 4 tripolar or 2
      pentapolar cuffs. Possible applications of the device are: improved defaecation
      and bladder voiding after spinal cord injury, by stimulation of the sacral motor
      roots; neuromodulation to reduce hyperreflexia without concomitant muscle
      contractions; in stroke patients, to enable balanced inversion-eversion while
      dorsiflexing the ankle by stimulating the peroneal nerve. It may also be used in
      chronic animal experiments.This paper describes the implant system, its hardware
      and communication protocol, and shows results from in vitro tests of the device
      and the first acute anodal-blocking experiments in pigs.

PMID- 11344006
TI  - ASIC or PIC? Implantable stimulators based on semi-custom CMOS technology or low
      power microcontroller architecture.
AB  - To gain a better understanding of the effects of chronic stimulation on mammalian
      muscles we needed to generate patterns of greater variety and complexity than
      simple constant-frequency or burst patterns. We describe here two approaches to
      the design of implantable neuromuscular stimulators that can satisfy these
      requirements. Devices of both types were developed and used in long-term
      experiments. The first device was based on a semi-custom Application Specific
      Integrated Circuit (ASIC). This approach has the advantage that the circuit can
      be completely tested at every stage of development and production, assuring a
      high degree of reliability. It has the drawback of inflexibility: the patterns
      are produced by state machines implemented in silicon, so each new set of
      patterns requires a fresh production run, which is costly and time-consuming. The
      second device was based on a commercial microcontroller (Microchip PIC16C84). The
      functionality of this type of circuit is specified in software rather than in
      silicon hardware, allowing a single device to be programmed for different
      functions. With the use of features designed to improve fault-tolerance we found
      this approach to be as reliable as that based on ASICs. The encapsulated devices
      can easily be accommodated subcutaneously on the flank of a rabbit and a recent
      version is small enough to implant into the peritoneal cavity of rats. The
      current devices are programmed with a predetermined set of 12 patterns before
      assembly; the desired pattern is selected after implantation with an electronic
      flash gun. The operating current drain is less than 40 microA.

PMID- 11344007
TI  - LD Pace II, an easily programmable device for cardiomyoplasty.
AB  - The efficacy of programmable devices depends heavily on being able to select
      parameter values matched to the individual patient's needs. In many cases,
      physicians fail to make use of all of the features of a device because of
      programming complexities. This paper presents a new cardiomyostimulator, "LD Pace
      II", emphasising in particular its novel features and the steps taken to make the
      behaviour of the device easy for the physician to program.

PMID- 11344008
TI  - Basic design and construction of the Vienna FES implants: existing solutions and
      prospects for new generations of implants.
AB  - We can distinguish 3 generations of FES implants for activation of neural
      structures: 1. RF-powered implants with antenna displacement dependent
      stimulation amplitude; 2. RF-powered implants with stabilised stimulation
      amplitude; and 3. battery powered implants. In Vienna an 8-channel version of the
      second generation type has been applied clinically to mobilisation of paraplegics
      and phrenic pacing. A 20-channel implant of the second generation type for
      mobilisation of paraplegics and an 8-channel implant of the third generation type
      for cardiac assist have been tested in animal studies. A device of completely new
      design for direct stimulation of denervated muscles is being tested in animal
      studies. There is a limited choice of technologically suitable biocompatible and
      bioresistant materials for implants. The physical design has to be anatomically
      shaped without corners or edges. Electrical conductors carrying direct current
      (D.C.) have to be placed inside a hermetic metal case. The established sealing
      materials, silicone rubber and epoxy resin, do not provide hermeticity and should
      only embed DC-free components. For electrical connections outside the hermetic
      metal case welding is preferable to soldering; conductive adhesives should be
      avoided. It is advisable to use a hydrophobic oxide ceramic core for telemetry
      antenna coils embedded in sealing polymer. Cleaning of all components before
      sealing in resin is of the utmost importance as well as avoidance of rapid
      temperature changes during the curing process.

PMID- 11344009
TI  - Development of functional electrical stimulators utilizing cochlear implant
      technology.
AB  - In 1983, R. Davis proposed the development of a functional electrical stimulator,
      based on multi-channel cochlear implant technology, for the restoration of
      function in spinal cord injured paraplegic subjects. In 1984, the US Veteran
      Administration funded the initial investigations including animal experiments and
      purchase of a FES stimulator based on the Nucleus 22 cochlear implant. In 1987,
      the US Food and Drug Administration approved an Investigational Device Exemption
      (IDE# G870142) for this FES project. In 1991, the first stimulator was implanted
      in a 21-year old male paraplegic subject (complete thoracic spinal cord lesion at
      level #10), who was subsequently able to stand and to perform one-handed tasks
      for up to 1h. In 1996-1997 development started on a new multi-function FES
      system. In 1998, a stimulator was implanted in a 35-year-old male paraplegic
      subject (complete thoracic spinal cord lesion at level #10). After 8 months of
      use providing multiple functions including bladder voiding, the implant's
      internal antenna wire broke. A modified implant (FES 24-B) is due to be implanted
      in July 2001.

PMID- 11344010
TI  - Daytime somnolence in patients with Parkinson's disease.
AB  - We studied daytime sleepiness in 160 patients with Parkinson's disease and 40
      normal subjects. We compared the prevalence of daytime sleepiness in patients who
      were taking levodopa alone, levodopa with bromocriptine, levodopa with
      ropinirole, and levodopa with pramipexole. We found that (1) all these anti
      Parkinson drugs can cause daytime sleepiness; (2) 'dozing off' correlated highly
      with 'falling asleep without warning'; (3) after statistical adjustment for
      confounding variables there was no significant difference among the risks for any
      of these anti-Parkinson drugs causing daytime somnolence.

PMID- 11344011
TI  - Modafinil for the treatment of excessive daytime sleepiness in Parkinson's
      disease: a case report.
AB  - We report a 59 year old woman with levodopa responsive Parkinson's disease who
      developed excessive daytime sleepiness [Epworth Sleepiness Scale (ESS) score of
      13]. Treatment with Modafinil 400mg daily within two weeks produced a subjective
      improvement in her daytime sleepiness (ESS score after treatment is 8) with no
      significant change in her PD motor symptomotology.

PMID- 11344012
TI  - Parkinsonism associated with autosomal dominant bilateral striopallidodentate
      calcinosis.
AB  - Bilateral striopallidodentate calcinosis (BSPDC, also known as Fahr's disease, a
      misnomer), is a rare disorder where bilateral, almost symmetric, calcium and
      other mineral deposits occur in subcortical nuclei and white matter. Neurological
      manifestations vary but movement disorders are the most common. Of the movement
      disorders, parkinsonism predominates. We describe 6 patients with BSPDC
      associated with parkinsonism. Of the 6 patients, one patient from an autosomal
      dominantly inherited family who responded to levodopa, showed Lewy bodies in
      substantia nigra neurons and changes consistent with BSPDC. Another patient, from
      the same family with clinical evidence of parkinsonism and radiological and
      neuropathological evidence of BSPDC, did not show Lewy bodies. Ten patients with
      BSPDC and parkinsonism (without evidence of parathyroid dysfunction) were found
      in the literature. When parkinsonism is associated with dementia and cerebellar
      signs, obtaining a CT scan may be helpful as BSPDC often presents with the above
      three conditions.

PMID- 11344013
TI  - Familial occurrence of Parkinson's disease in a community-based case-control
      study.
AB  - Purpose: To study the occurrence of Parkinson's disease (PD) in the relatives of
      parkinsonian patients (n=119), and of their matched controls (n=238).Scope: More
      patients reported a positive family history of PD in their first degree
      relatives, compared to their controls (OR 2.7, 95% CI 1.3-5.9), and the incidence
      of PD among those relatives was also significantly higher (OR 1.4, 95% CI 1.1
      1.8).Conclusions: Familial occurrence of PD is not necessarily a sign of genetic
      mechanisms in the etiology of PD. Shared environment with common risk factors
      might be even more important.

PMID- 11344014
TI  - Alternating two finger tapping with contralateral activation is an objective
      measure of clinical severity in Parkinson's disease and correlates with PET
AB  - We explored an objective method of measuring clinical severity of Parkinson's
      disease. Eighty-six patients with PD and 136 healthy subjects were studied. We
      serially carried out four types of finger tapping (FT) using a computerized drum
      machine: (i) repetitive one-finger tapping with an index-finger (F1K1); (ii) one
      finger tapping on two keys separated by 20cm (F1K2); (iii) alternate tapping with
      index and middle fingers on two adjacent keys (F2K2); and (iv) F2K2 with
      contralateral activation (aF2K2). Analyses on FT included: (i) age and gender
      effects in healthy volunteers and Parkinson's disease; (ii) comparison between
      Parkinson patients and controls of similar age distribution; (iii) correlation
      with the Purdue Pegboard and Modified Columbia Scale in Disease; and (iv) in a
      subset of patients in whom PET scans were performed (n=30), correlation with 18F
      DOPA uptake constant (Ki). In healthy subjects, there was a negative age effect
      on FT scores and a gender effect, with males scoring higher than females. All FT
      scores were significantly lower in the Parkinson patients, correlated with Purdue
      Peg Board, and inversely with the duration of illness, and with the Modified
      Columbia Scale. The 18F-DOPA Ki correlated significantly with aF2K2 (p=0.024),
      less so with PPB (p=0.038), but not with the Modified Columbia Scale. We conclude
      that alternating two-finger tapping with contralateral hand activation is a
      simple, objective test for measuring the severity of Parkinson's disease.

PMID- 11344015
TI  - Iron accumulation in the substantia nigra of autosomal recessive juvenile
      parkinsonism (ARJP).
AB  - Autosomal recessive juvenile parkinsonism (ARJP) is a distinct clinical and
      genetic entity characterized by highly selective neuronal death in the substantia
      nigra (SN) and locus coeruleus neurons without Lewy body formation. The mechanism
      of neuronal death of ARJP is still unknown. Our study demonstrated that iron
      staining was more intense in ARJP than in both controls and sporadic Parkinson's
      disease (PD), and there were differences in the pattern of distribution of iron
      staining between ARJP and PD. In addition neurites of SN in ARJP showed intense
      iron staining. Thus, we postulate that oxidative stress may play an important
      role in the neurodegeneration that occurs in ARJP.

PMID- 11344016
TI  - Obsessive-compulsive-like behavioral changes in pure akinesia.
AB  - Pure akinesia is a disorder characterized by profound freezing in the absence of
      rigidity or tremor that is not improved by levodopa therapy. We report two cases
      of pure akinesia who developed obsessive-compulsive-disorder- (OCD-) like
      behavior during their illness. Although the pathophysiological mechanism
      underlying freezing is unclear, the coexistence of pure akinesia and OCD-like
      behavior suggests that both symptoms have a common pathological basis in these
      two cases, presumably damage to the pallidum.

PMID- 11344017
TI  - Ipsilateral putamen hyperintensity on T1-weighted MRI in non-ketotic
      hyperglycemia with hemiballism-hemichorea: a case report.
AB  - Movement disorders are often caused by lesions in the contralateral basal
      ganglia. This report presents an elderly woman with hemiballism-hemichorea
      induced by non-ketotic hyperglycemia, whose brain CT revealed a hyperdense lesion
      over the ipsilateral putamen. Concomitantly, MR image revealed a putaminal
      hyperintensity on T1-weighted image and hypointensity on T2-weighted image. A
      follow-up brain CT 4months after remission of the hyperkinesia revealed that the
      abnormal intensity had been completely resolved.

PMID- 11344018
TI  - Spasmodic torticollis and reproductive function in women.
AB  - This investigation assessed a possible relationship between idiopathic spasmodic
      torticollis (ST) and reproductive function in women. Fifth decade ST onset, the
      peak decade for menopause, was over represented. Menstrual exacerbation of
      symptoms was significantly more common than in controls. Oral contraceptive use
      and pregnancy did not have adverse effects. Reproductive disorders and
      hysterectomy were significantly more common than in neurological and normal
      controls. The possibility that ST onset and severity may relate to reproductive
      state and hormonal factors warrants further investigation.

PMID- 11344019
TI  - Quantitative assessment of parkinsonian sialorrhea and results of treatment with
      botulinum toxin.
AB  - Aim: To assess quantitatively sialorrhea in Parkinson's disease (PD) and the
      efficacy of botulinum toxin (BOTOX) in its treatment.Material: 11 patients with a
      clinical diagnosis of idiopathic PD and drooling were assessed at least two
      points on the UPDRS Part II and 14 control subjects.Methods: Salivation was
      measured by weighing dental rolls before, and 2min after, insertion at six points
      of highest secretion of saliva in the mouth (buccal vestibule, and sublingual
      area). PD patients were assessed before and 1 week after injections of five units
      of BOTOX into each parotid salivary gland and the results were compared to the
      salivation production of controls.Results: Average secretion of saliva in PD
      patients was significantly higher than in controls-0.39+/-0.4g/2min. (range: 0.02
      1.82) vs 0.19+/-0.16g/2min. (range: 0.02-0.98) (P=0.03). After treatment, the
      average secretion of saliva in PD patients decreased to 0.25+/-0.26g/2min.
      (range: 0.004-0.99) and did not differ significantly from controls. Nine patients
      improved also according to UPDRS. No side effects were observed in any of the
      patients injected.Conclusion: Botulinum toxin may be an effective and safe
      treatment of parkinsonian sialorrhea.

PMID- 11344020
TI  - Neutrophil elastase inhibitors for cystic fibrosis.

PMID- 11344022
TI  - Intelligent inhalers for systemic administration?

PMID- 11344021
TI  - New genes linked to schizophrenia.

PMID- 11344025
TI  - The Internet, pharmaceuticals and the law.

PMID- 11344024
TI  - Key industry directors and companies pick up awards.

PMID- 11344026
TI  - Location is key - recent progress in single-cell-based high-throughput assays.

PMID- 11344027
TI  - Drug discoverers - you need us! - Reply.

PMID- 11344028
TI  - One-third of Swedish food plants has anti-inflammatory records.

PMID- 11344029
TI  - Proteomics: new technologies and their applications.

PMID- 11344030
TI  - Current progress on new therapies for Alzheimer's disease.

PMID- 11344031
TI  - Physical stabilization of DNA-based therapeutics.
AB  - The development of non-viral vectors for gene delivery has primarily focused on
      improving the efficiency of gene transfer in vivo. Although there is clearly a
      need to improve delivery efficiency, studies also indicate that the physical
      stability of non-viral vectors is not nearly adequate for a marketable
      pharmaceutical product. Here, we describe the different strategies that have been
      used to enhance stability and discuss the mechanisms by which prolonged
      stabilization (>2 years) might be achieved.

PMID- 11344032
TI  - High-throughput purification of compound libraries.
AB  - Synthesis of combinatorial libraries by parallel synthesis, followed by high-
      throughput biological screening, is the new paradigm for drug discovery. Purity
      of these libraries is an important consideration to obtain high-quality assay
      data. Liquid-liquid extraction and solid-phase capture reagents are useful in
      special cases for small numbers of compounds. However, for libraries of a few
      thousand compounds, HPLC is a viable alternative. Beyond these numbers, factors
      such as solvent requirements, the number of fractions and tracking become
      prohibitive. Supercritical fluid chromatography has been successfully employed in
      automated purification instrumentation and is expected to be capable of purifying
      libraries of tens-of-thousands of compounds.

PMID- 11344033
TI  - Matrix metalloproteinases in cancer invasion, metastasis and angiogenesis.
AB  - Matrix metalloproteinases (MMPs) are a family of proteinases that play an
      important role in cancer as well as in numerous other diseases. In this article,
      we summarize the current views on the role of MMPs in cancer with respect to
      invasion, metastasis and angiogenesis. A positive correlation between tumor
      progression and the expression of multiple MMP family members in tumor tissues
      has been demonstrated in numerous human and animal studies. It has been assumed
      that cancer cells are responsible for producing the MMPs in human tumors.
      However, recent evidence suggests that tumor cells have docking sites that bind
      stromal-cell-secreted MMPs. Furthermore, the role of MMPs produced by endothelial
      cells, especially MMP-2 and MT1-MMP, appear to be crucial for tumor angiogenesis,
      which is a requirement for cancer growth and dissemination.

PMID- 11344034
TI  - Recent progress in tissue engineering.
AB  - Tissue engineering is a newly emerging biomedical technique that involves the
      artificial manipulation of cells to promote tissue and organ regeneration. Its
      medical significance will undoubtedly increase in the 21st century. This review
      summarizes recent progress that has been made in tissue engineering as well as
      its future implications.

PMID- 11344036
TI  - Novel antitumour molecules.

PMID- 11344035
TI  - Monitor: molecules and profiles.
AB  - Monitor provides an insight into the latest developments in drug discovery
      through brief synopses of recent presentations and publications together with
      expert commentaries on the latest technologies. There are two sections: Molecules
      summarizes the chemistry and the pharmacological significance and biological
      relevance of new molecules reported in the literature and on the conference
      scene; Profiles offers commentary on promising lines of research, emerging
      molecular targets, novel technology, advances in synthetic and separation
      techniques and legislative issues.

PMID- 11344037
TI  - Drug delivery.

PMID- 11344038
TI  - The discovery of mRNA.

PMID- 11344039
TI  - Chromosome aberration assays in Pisum for the study of environmental mutagens.
AB  - From a literature survey, 117 chemicals are tabulated that have been assayed in
      179 assays for their clastogenic effects in Pisum. Of the 117 chemicals that have
      been assayed, 65 are reported at giving a positive reaction (i.e. causing
      chromosome aberrations), 30 positive with a dose response, five borderline
      positive. Seventeen chemicals gave a negative response. Eighty-one percent of the
      chemicals gave a definite positive response. A c-mitotic effect was detected from
      treatment with 17 chemicals. In addition to the above tabulation of chemicals, 39
      chemicals have been reported with an antimitotic effect. Thirteen assays have
      been recorded for five types of radiation, which with the exception of ultrasound
      reacted positively. The results of assays with 38 chemicals and/or radiations in
      combined treatments, as well as 15 chemicals and three types of radiations that
      induce somatic mutations are tabulated. The Pisum sativum (2n=14) bioassay has
      been shown to be a very good plant bioassay for assessing chromosome damage both
      in mitosis and meiosis for somatic mutations induced by chemicals, radiations,
      and environmental pollutants. For some chemicals, the Pisum assay is not as
      sensitive in assessing clastogenicity as the Allium assay, although this should
      be considered in relative terms. Pisum fulvum (2n=14) has been used in
      clastogenic studies also, but to a much lesser extent.

PMID- 11344040
TI  - Mitochondrial DNA in human malignancy.
AB  - Alterations in expression of mitochondrial DNA (mtDNA)-encoded polypeptides
      required for oxidative phosphorylation and cellular ATP generation may be a
      general characteristic of cancer cells. Mitochondrial DNA has been proposed to be
      involved in carcinogenesis because of high susceptibility to mutations and
      limited repair mechanisms in comparison to nuclear DNA. Since mtDNA lacks
      introns, it has been suggested that most mutations will occur in coding sequences
      and subsequent accumulation of mutations may lead to tumor formation. The
      mitochondrial genome is dependent upon the nuclear genome for transcription,
      translation, replication and repair, but precise mechanisms for how the two
      genomes interact and integrate with each other are poorly understood. In solid
      tumors, elevated expression of mtDNA-encoded subunits of the mitochondrial
      electron respiratory chain may reflect mitochondrial adaptation to perturbations
      in cellular energy requirements. In this paper, we review mitochondrial genomic
      aberrations reported in solid tumors of the breast, colon, stomach, liver,
      kidney, bladder, head/neck and lung as well as for hematologic diseases such as
      leukemia, myelodysplastic syndrome and lymphoma. We include data for elevated
      expression of mtDNA-encoded electron respiratory chain subunits in breast, colon
      and liver cancers and also the mutations reported in cancers of the colon,
      stomach, bladder, head/neck and lung. Finally, we examine the role of reactive
      oxygen species (ROS) generated by mitochondria in the process of carcinogenesis.

PMID- 11344041
TI  - Anti-genotoxicity of galangin as a cancer chemopreventive agent candidate.
AB  - Flavonoids are polyphenolic compounds that are present in plants. They have been
      shown to possess a variety of biological activities at non-toxic concentrations
      in organisms. Galangin, a member of the flavonol class of flavonoid, is present
      in high concentrations in medicinal plants (e.g. Alpinia officinarum) and
      propolis, a natural beehive product. Results from in vitro and in vivo studies
      indicate that galangin with anti-oxidative and free radical scavenging activities
      is capable of modulating enzyme activities and suppressing the genotoxicity of
      chemicals. These activities will be discussed in this review. Based on our
      review, galangin may be a promising candidate for cancer chemoprevention.

PMID- 11344042
TI  - A review of the genotoxicity of marketed pharmaceuticals.
AB  - Information in the 1999 Physician's Desk Reference as well as from the peer
      reviewed published literature was used to evaluate the genotoxicity of marketed
      pharmaceuticals. This survey is a compendium of genotoxicity information and a
      means to gain perspective on the inherent genotoxicity of structurally diverse
      pharmaceuticals. Data from 467 marketed drugs were collected. Excluded from
      analysis were anti-cancer drugs and nucleosides, which are expected to be
      genotoxic, steroids, biologicals and peptide-based drugs. Of the 467 drugs, 115
      had no published gene-tox data. This group was comprised largely of acutely
      administered drugs such as antibiotics, antifungals, antihistamines decongestants
      and anesthetics. The remaining 352 had at least one standard gene-tox assay
      result. Of these, 101 compounds (28.7%) had at least one positive assay result in
      the pre-ICH/OECD standard four-test battery (bacterial mutagenesis, in vitro
      cytogenetics, mouse lymphoma assay (MLA), in vivo cytogenetics). Per assay type,
      the percentage of positive compounds was: bacterial mutagenesis test, 27/323
      (8.3%); in vitro cytogenetics 55/222 (24.8%); MLA 24/96 (25%); in vivo
      cytogenetics 29/252 (11.5%). Of the supplemental genetic toxicology test findings
      reported, the sister chromatid exchange (SCE) assay had the largest percentage of
      positives 17/39 (43.5%) and mammalian mutagenesis assays (excluding MLA) had the
      lowest percentage of positives 2/91 (2.2%). The predictive value of genetic
      toxicology findings for 2-year bioassay outcomes is difficult to assess since
      carcinogenicity can occur via non-genotoxic mechanisms. Nevertheless, the
      following survey findings were made: 201 drugs had both gene-tox data and rodent
      carcinogenicity data. Of these, 124 were negative and 77 were equivocal or
      positive for carcinogenicity in at least 1 gender/1 species. Of the 124 non
      carcinogens, 100 had no positive gene-tox findings. Of the remaining 24, 19 were
      positive in in vitro cytogenetics assays. Among the 77 compounds that exhibited
      equivocal or positive effects in carcinogenesis studies, 26 were positive in gene
      tox assays and 51 were negative. Of the 51 negatives, 47 had multiple negative
      gene-tox assay results suggesting that these are probably non-genotoxic
      carcinogens. Statistical analyses suggested that no combination of gene-tox
      assays provided a higher predictivity of rodent carcinogenesis than the bacterial
      mutagenicity test itself.

PMID- 11344043
TI  - Genetic toxicology of a paradoxical human carcinogen, arsenic: a review.
AB  - Arsenic is widely distributed in nature in air, water and soil in the form of
      either metalloids or chemical compounds. It is used commercially, as pesticide,
      wood preservative, in the manufacture of glass, paper and semiconductors.
      Epidemiological and clinical studies indicate that arsenic is a paradoxical human
      carcinogen that does not easily induce cancer in animal models. It is one of the
      toxic compounds known in the environment. Intermittent incidents of arsenic
      contamination in ground water have been reported from several parts of the world.
      Arsenic containing drinking water has been associated with a variety of skin and
      internal organ cancers. The wide human exposure to this compound through drinking
      water throughout the world causes great concern for human health. In the present
      review, we have attempted to evaluate and update the mutagenic and genotoxic
      effects of arsenic and its compounds based on available literature.

PMID- 11344044
TI  - The bisphosphonate zoledronate decreases type II collagen breakdown in patients
      with Paget's disease of bone.
AB  - Bisphosphonates have been suggested to be partially chondroprotective in animal
      models of arthritis. The aim of this study was to assess the short-term effect of
      the bisphosphonate zoledronate on type II collagen degradation in patients with
      Paget's disease of bone. Twenty-six patients with active Paget's disease who were
      a part of a double-blind, placebo-controlled, randomized study comparing the
      effects of several doses of a single injection of zoledronate, a potent
      bisphosphonate, were studied. Type II collagen destruction was assessed by
      urinary levels of type II collagen C-telopeptide (CTX-II) using a new
      immunoassay. Bone resorption was assessed by measuring the urinary excretion of
      nonisomerized type I collagen C-telopeptide (alpha CTX-I). Biochemical markers
      were measured at baseline and 5, 10, 30, and 60 days after injection. At
      baseline, no significant increase of CTX-II was observed in patients with Paget's
      disease compared with a group of 27 gender-and age-matched controls, in contrast
      to the ninefold (p < 0.0001) increase of urinary alpha CTX-I. After a single
      intravenous injection of zoledronate (200 or 400 microg), urinary CTX-II
      transiently decreased by a median of 25% 5 days after the injection of
      zoledronate (p = 0.0023 vs. placebo), then increased to pretreatment levels after
      10 days. In contrast, urinary alpha CTX-I decreased within 5 days with a maximal
      decrease of 51% at day 10 (p < 0.001 vs. baseline and placebo), and levels
      remained suppressed during the 2 months of the study. Zoledronate not only
      reduces bone turnover but also directly decreases type II collagen degradation in
      patients with Paget's disease, suggesting that bisphosphonates may have
      chondroprotective effects in humans. Measurement of type II collagen breakdown by
      a new urinary biochemical marker may be useful for in vivo assessment of the
      effects of drugs that potentially inhibit cartilage destruction.

PMID- 11344045
TI  - Visualization of bisphosphonate-induced caspase-3 activity in apoptotic
      osteoclasts in vitro.
AB  - Bisphosphonates inhibit osteoclast-mediated bone resorption by mechanisms that
      have only recently become clear. Whereas nitrogen-containing bisphosphonates
      affect osteoclast function by preventing protein prenylation (especially
      geranylgeranylation), non-nitrogen-containing bisphosphonates have a different
      molecular mechanism of action. In this study, we demonstrate that nitrogen
      containing bisphosphonates (risedronate, alendronate, pamidronate, and zoledronic
      acid) and non-nitrogen-containing bisphosphonates (clodronate and etidronate)
      cause apoptosis of rabbit osteoclasts, human osteoclastoma-derived osteoclasts,
      and human osteoclast-like cells generated in cultures of bone marrow in vitro.
      Osteoclast apoptosis was shown to involve characteristic morphological changes,
      loss of mitochondrial membrane potential, and the activation of caspase-3-like
      proteases capable of cleaving peptide substrates with the sequence DEVD. Caspase
      3-like activity could be visualized in unfixed, dying osteoclasts and osteoclast
      like cells using a cell-permeable, fluorogenic substrate. Bisphosphonate-induced
      osteoclast apoptosis was dependent on caspase activation, because apoptosis
      resulting from alendronate, clodronate, or zoledronic acid treatment was
      suppressed by zVAD-fmk, a broad-range caspase inhibitor, or by SB-281277, a
      specific isatin sulfonamide inhibitor of caspase-3/-7. Furthermore, caspase-3
      (but not caspase-6 or caspase-7) activity could be detected and quantitated in
      lysates from purified rabbit osteoclasts, whereas the p17 fragment of active
      caspase-3 could be detected in human osteoclast-like cells by immunofluorescence
      staining. Caspase-3, therefore, appears to be the major effector caspase
      activated in osteoclasts by bisphosphonate treatment. Caspase activation and
      apoptosis induced by nitrogen-containing bisphosphonates are likely to be the
      consequence of the loss of geranylgeranylated rather than farnesylated proteins,
      because the ability to cause apoptosis and caspase activation was mimicked by
      GGTI-298, a specific inhibitor of protein geranylgeranylation, whereas FTI-277, a
      specific inhibitor of protein farnesylation, had no effect on apoptosis or
      caspase activity.

PMID- 11344046
TI  - Tumor necrosis factor-alpha cooperates with receptor activator of nuclear factor
      kappaB ligand in generation of osteoclasts in stromal cell-depleted rat bone
      marrow cell culture.
AB  - A member of the tumor necrosis factor (TNF) family, receptor activator of nuclear
      factor kappaB ligand (RANKL; also known as ODF, OPGL, and TRANCE), plays critical
      roles in osteoclast differentiation and activation in the presence of macrophage
      colony-stimulating factor (M-CSF). Recently, TNF-alpha has also been shown to
      induce the formation of multinucleated osteoclast-like cells (MNCs) in the
      presence of M-CSF from mouse macrophages. We demonstrated that mononuclear
      preosteoclast-like cells (POCs) were formed in the presence of conditioned medium
      of osteoblastic cells in a rat bone marrow culture depleted of stromal cells.
      Using this culture system, in this study we examined whether TNF-alpha affects
      differentiation into POCs from hematopoietic progenitor cells. Human TNF-alpha
      (hTNF-alpha) markedly stimulated the formation of POCs. Moreover, a concentration
      as low as 0.005 ng/mL of hTNF-alpha increased the level of mRNA for calcitonin
      receptor (CTR) and cathepsin-K of POCs. The POCs induced by hTNF-alpha formed
      MNCs, which showed dentine-resorbing activity after coculture with primary
      osteoblasts. Stimulation was observed after 24 h of treatment with hTNF-alpha
      only on day 1 or day 2 of the culture. After 24 h of hTNF-alpha treatment,
      expression of the receptor activator of nuclear factor kappaB (RANK) mRNA was
      markedly increased. The addition of soluble RANKL (sRANKL) to the preformed POCs
      efficiently induced MNCs. Interestingly, treatment of bone marrow cells with hTNF
      alpha and sRANKL synergistically augmented the formation of MNCs. This formation
      was abolished by the addition of human osteoprotegerin (hOPG). These results
      suggest that cooperation of TNF-alpha and RANKL is important for
      osteoclastogenesis.

PMID- 11344047
TI  - Cortisol inhibits the differentiation and apoptosis of osteoblasts in culture.
AB  - Glucocorticoids decrease the replication of cells of the osteoblastic lineage and
      the function of the osteoblast. However, under certain conditions, they enhance
      the differentiation of osteoblastic cells, an effect that appears contradictory
      to their inhibitory actions on cell function. In this study we examine the
      effects of cortisol on the proliferation, differentiation, and fate of
      osteoblastic enriched cells from 22-day-old fetal rat calvariae (osteoblastic
      cells) in the absence and presence of beta-glycerophosphate. In the absence of
      beta-glycerophosphate, there was a progressive accumulation of DNA and cells,
      which was impaired by cortisol. In the presence of beta-glycerophosphate, there
      was an initial accumulation of DNA and cells followed by a marked decline that
      was prevented by cortisol. Despite the sustained number of cells, cortisol did
      not affect their mineralization, and inhibited Core binding factor a1 (Cbfa1),
      but not alkaline phosphatase, osteocalcin, or type I collagen transcripts. The
      decrease in cell number by cortisol observed in the absence of beta
      glycerophosphate was due to a decrease in DNA synthesis, whereas the increase in
      cell number observed in the presence of beta-glycerophosphate was due to a
      relative increase in DNA synthesis and a decrease in apoptosis as determined by
      DNA fragmentation and acridine orange staining of the cells. This was correlated
      by a decrease in transcripts of proapoptotic genes and caspase 3 activity, and an
      increase of antiapoptotic genes. In conclusion, cortisol decreases the
      replication of cells of the osteoblastic lineage, but under conditions of
      differentiation/mineralization, cortisol prevents terminal differentiation of the
      cells and maintains an immature cell population.

PMID- 11344048
TI  - Activation of mitogen-activated protein kinase cascades is involved in regulation
      of bone morphogenetic protein-2-induced osteoblast differentiation in pluripotent
      C2C12 cells.
AB  - Bone morphogenetic protein (BMP)-2, a member of the transforming growth factor
      beta (TGF-beta) superfamily, is able to induce osteoblastic differentiation of
      C2C12 cells. Both Smad and mitogen-activated protein kinase (MAPK) pathways are
      essential components of the TGF-beta superfamily signaling machinery. Although
      Smads have been demonstrated to participate in the BMP-2-induced osteoblastic
      differentiation of C2C12 cells, the role of MAPK has not been addressed. This
      report shows that BMP-2 activates ERK and p38, but not JNK, in C2C12 cells.
      Pretreatment of cells with the p38 inhibitor, SB203580, dramatically reduced BMP
      2-induced expression of the osteoblast markers alkaline phosphatase (ALP) and
      osteocalcin (OC). Nevertheless, overexpression of MKK3, a protein kinase that
      phosphorylates and activates p38, failed to induce ALP or OC expression in the
      absence of BMP-2, indicating that p38 activation is necessary but not sufficient
      for the acquisition of the osteoblast phenotype by these cells. Although ALP
      induction was increased slightly in the presence of PD-98059, a selective
      inhibitor of the ERK cascade, this compound significantly inhibited both steady
      state and BMP-2-induced OC RNA levels. Our results indicate that p38 and ERK
      cascades play a crucial role in the osteoblast differentiation of C2C12 cells
      mediated by BMP-2.

PMID- 11344049
TI  - The effect of bone morphogenetic protein-2 expression on the early fate of
      skeletal muscle-derived cells.
AB  - The identification of bone morphogenetic proteins (BMPs) has stimulated intense
      interest in BMP delivery approaches. Ex vivo BMP-2 gene delivery has recently
      been described using skeletal muscle-derived cells. Skeletal muscle-derived
      cells, because of proven efficient transgene delivery and osteocompetence,
      represent an attractive cell population on which to base ex vivo BMP-2 gene
      delivery. However, the early in vivo fate of BMP-2-expressing muscle-derived
      cells is unknown. This study investigates the in vivo effects of BMP-2 secretion
      on skeletal muscle-derived cells in terms of cell survival and cell
      differentiation. The first experiment compared survival of BMP-2-expressing cells
      with control cells during the first 48 h after in vivo implantation. The results
      demonstrate that BMP-2 secretion did not adversely affect cell survival 8, 24, or
      48 h after intramuscular implantation. The second experiment histologically
      compared the fate of BMP-2-expressing muscle-derived cells to the same cells not
      expressing BMP-2. The results show that BMP-2 expression prevented in vivo
      myogenic differentiation and promoted osteogenic differentiation of the
      transduced cells. This study further supports the existence of osteoprogenitor
      cells residing within skeletal muscle. Moreover, it is demonstrated that BMP-2
      secretion does not adversely affect early cell survival of muscle-derived cells.
      These data are important for future investigations into BMP-2 gene delivery
      approaches to the musculoskeletal system.

PMID- 11344050
TI  - Extracellular nucleotide signaling: a mechanism for integrating local and
      systemic responses in the activation of bone remodeling.
AB  - Bone turnover occurs at discreet sites in the remodeling skeleton. The focal
      nature of this process indicates that local cues may facilitate the activation of
      bone cells by systemic factors. Nucleotides such as adenosine triphosphate (ATP)
      are locally released, short-lived, yet potent extracellular signaling molecules.
      These ligands act at a large family of receptors-the P2 receptors, which are
      subdivided into P2Y and P2X subtypes based on mechanism of signal transduction.
      Nucleotides enter the extracellular milieu via non-lytic and lytic mechanisms
      where they activate multiple P2 receptor types expressed by both osteoblasts and
      osteoclasts. In this review the release of ATP by bone cells is discussed in the
      context of activation of bone remodeling. We provide compelling evidence that
      nucleotides, acting via P2Y receptors, are potent potentiators of parathyroid
      hormone-induced signaling and transcriptional activation in osteoblasts. The
      provision of a mechanism to induce activation of osteoblasts above a threshold
      attained by systemic factors alone may facilitate focal remodeling and address
      the paradox of why systemic regulators like PTH exert effects at discreet sites.

PMID- 11344051
TI  - The mouse osteopetrotic grey-lethal mutation induces a defect in osteoclast
      maturation/function.
AB  - The osteopetrotic grey-lethal (gl) mouse mutant displays many similarities to the
      human malignant autosomal-recessive form of osteopetrosis. In this study, we show
      that the gl osteopetrotic bone phenotype is characterized by the presence of
      numerous differentiated multinucleated osteoclasts. A significant increase in the
      number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts was
      detected in vivo, suggesting induction of differentiation in the osteoclast
      lineage as a compensatory mechanism. These gl osteoclast cells demonstrated a
      defective cytoskeletal reorganization and an underdeveloped ruffled border, a
      membrane structure essential for active bone resorption. Accordingly, resorption
      activity of these cells is markedly impaired by four- to tenfold as evaluated
      with the pit formation assay. This low bone resorption in gl osteoclasts is
      highly reminiscent of the loss in key enzymes, V-ATPase or cathepsin-K, and in
      signaling factors, Src or TRAF-6, which were shown not to be significantly
      altered in gl osteoclasts. Thus, independently of a deficiency in V-ATPase, Src,
      cathepsin-K, and TRAF-6, the gl mutation results in increased number of
      osteoclasts, characterized by a disrupted cytoskeleton and an underdeveloped
      ruffled border.

PMID- 11344052
TI  - Effects of suppressed bone turnover by bisphosphonates on microdamage
      accumulation and biomechanical properties in clinically relevant skeletal sites
      in beagles.
AB  - We recently demonstrated that suppression of bone remodeling allows microdamage
      to accumulate, leading to reduced bone toughness in the rib cortex of dogs. This
      study evaluates the effects of reduced bone turnover produced by bisphosphonates
      on microdamage accumulation and biomechanical properties at clinically relevant
      skeletal sites in the same dogs. Thirty-six female beagles, 1-2 years old, were
      divided into three groups. The control group was treated daily for 12 months with
      saline vehicle (CNT). The remaining two groups were treated daily with
      risedronate at a dose of 0.5 mg/kg per day (RIS), or alendronate at 1.0 mg/kg per
      day (ALN) orally. The doses of these bisphosphonates were six times the clinical
      doses approved for treatment of osteoporosis in humans. After killing, the L-1
      vertebra was scanned by dual-energy X-ray absorptiometry (DXA), and the L-2
      vertebra and right ilium were assigned to histomorphometry. The L-3 vertebra,
      left ilium, Th-2 spinous process, and right femoral neck were used for
      microdamage analysis. The L-4 vertebra and Th-1 spinous process were mechanically
      tested to failure in compression and shear, respectively. One year treatment with
      risedronate or alendronate significantly suppressed trabecular remodeling in
      vertebrae (RIS 90%, ALN 95%) and ilium (RIS 76%, ALN 90%) without impairment of
      mineralization, and significantly increased microdamage accumulation in all
      skeletal sites measured. Trabecular bone volume and vertebral strength increased
      significantly following 12 month treatment. However, normalized toughness of the
      L-4 vertebra was reduced by 21% in both RIS (p = 0.06) and ALN (p = 0.05) groups.
      When the two bisphosphonate groups were pooled in a post hoc fashion for
      analysis, this reduction in toughness reached statistical significance (p =
      0.02). This study demonstrates that suppression of trabecular bone turnover by
      high doses of bisphosphonates is associated with increased vertebral strength,
      even though there is significant microdamage accumulation and a reduction in the
      intrinsic energy absorption capacity of trabecular bone.

PMID- 11344053
TI  - Changes in bone turnover following gonadotropin-releasing hormone (GnRH) agonist
      administration and estrogen treatment in cynomolgus monkeys: a short-term model
      for evaluation of antiresorptive therapy.
AB  - In this study we determine the early time course of estrogen deficiency-induced
      bone loss in the cynomolgus monkey and examine the potential of this method for
      evaluating antiresorptive therapies. In two groups of animals, estrogen
      deficiency was induced by the administration of a gonadotropin-releasing hormone
      agonist (GnRHa) and bone turnover was measured using biochemical markers. Two
      weeks after receiving GnRHa, serum estradiol decreased to below the detection
      limit in most animals and remained there through 6 months or until estrogen
      replacement started (months 4-6). Relative to untreated animals, urinary
      deoxypyridinoline (dPyr), as well as C- and N-telopeptides of type I collagen,
      were significantly elevated 4 weeks after receiving GnRHa. Serum osteocalcin
      increased in GnRHa-treated animals as early as week 4 and the level was
      significantly higher than in untreated control animals from weeks 8-24. Estradiol
      treatment returned all measures of bone turnover to control levels within 2
      weeks. The use of biochemical markers as surrogates of bone turnover and loss was
      validated by measurement of bone mineral density (BMD), which showed a
      significant reduction at 6 months in estrogen-deficient animals. However, lumbar
      BMD in animals that received GnRHa and estradiol was similar to that in animals
      that had not received GnRHa. In conclusion, a monthly depot injection of GnRHa
      resulted in increased bone turnover due to estrogen deficiency, as early as 4
      weeks after treatment. Estrogen administration returned bone turnover to control
      levels in 2 weeks. This method represents a valid model for evaluating
      antiresorptive agents in the short term in a nonhuman primate. Furthermore, the
      data suggest that changes in biochemical markers in response to antiresorptive
      therapy in humans may be detectable at much earlier timepoints than commonly
      used.

PMID- 11344054
TI  - Effects of human parathyroid hormone (1-34), LY333334, on bone mass, remodeling,
      and mechanical properties of cortical bone during the first remodeling cycle in
      rabbits.
AB  - We have previously shown that parathyroid hormone (PTH) increases cortical bone
      mass and mechanical strength of female rabbits after 140 days of treatment.
      However, cortical porosity was also shown to increase. If cortical porosity
      increases prior to the change in geometry, there may be a transient decrease in
      cortical bone strength that could make the bone more susceptible to fracture in
      the early phase of treatment. The purpose of this study is to examine the effects
      of PTH on the remodeling dynamics and mechanical properties of cortical bone in
      rabbits, which exhibit haversian remodeling, during the first remodeling cycle
      after the initiation of treatment. Fifty 9-month-old intact female New Zealand
      white rabbits were randomized into five groups. A baseline control group was
      killed at the start of the experiment. The two PTH-treated groups were given
      human PTH(1-34) at 10 microg/kg daily subcutaneously for 35 (P35) or 70 (P70)
      days. Two respective age-matched control groups (V35, V70) were injected with
      vehicle. Histomorphometry of the cortical bone in the tibial midshaft showed
      that, although intracortical activation frequency was significantly increased by
      PTH at 35 days, there was no significant increase of cortical porosity in the
      first remodeling cycle (70 days). Moreover, stimulation of cortical surface bone
      formation in the treated animals led to significantly greater cortical area and
      greater bone strength in both P35 and P70. We conclude that, although
      intracortical remodeling increases within the first remodeling period (70 days)
      in animals treated with 10 microg/kg PTH, the greater cortical area due to
      acceleration of bone formation on cortical surfaces increases cortical bone
      strength. There is no mechanical risk during the first remodeling cycle
      associated with intermittent PTH treatment in animals with normal bone mass.

PMID- 11344055
TI  - Inaccuracies inherent in dual-energy X-ray absorptiometry in vivo bone mineral
      densitometry may flaw osteopenic/osteoporotic interpretations and mislead
      assessment of antiresorptive therapy effectiveness.
AB  - New, anatomically realistic simulation studies based on a cadaveric lumbar
      vertebra and a broad range of soft tissue anthropometric representations have
      quantitatively delineated inaccuracies inherent in dual-energy X-ray
      absorptiometry (DXA) in vivo bone mineral density (BMD) methodology. It is found
      that systematic inaccuracies in DXA BMD measurements may readily exceed +/-20% at
      typical in vivo lumbar vertebral sites, especially for osteopenic/osteoporotic,
      postmenopausal, and elderly patients. These findings are quantitatively compared
      with extensive clinical evidence of strong, positive correlations between soft
      tissue anthropometrics and DXA in vivo BMD upon which prior significant bone
      biology interpretations and implications have been based. The agreement is found
      to be both qualitatively and quantitatively excellent. Moreover, recent extensive
      multicenter clinical studies have also exposed new facets of strong linkages
      between body mass/percent body fat/body mass index (BMI) and DXA-measured BMD
      that are particularly relevant to osteopenia/osteoporosis and remedial
      effectiveness of antiresorptive drug therapy. These seemingly disparate and
      unrelated diagnostic and prognostic aspects of clinically observed associations
      between soft tissue anthropometrics and measured vertebral BMD are, in this
      study, self-consistently shown to share the common origin of being manifestations
      of systematic inherent inaccuracies in DXA in vivo BMD methodology, without the
      need to invoke any underlying biologically causal mechanism(s). These
      inaccuracies arise principally from absorptiometric disparities between the intra
      and extraosseous soft tissues within the DXA scan region of interest. The
      present evaluative comparisons are based exclusively on an incisive and diverse
      body of clinical data that appears difficult to dismiss or discount. Previous
      invocations of biologically causal mechanisms responsible for this broad range of
      observations linking body mass, percent body fat, and/or BMI to measured BMD now
      appear questionable. This doubtful status has also been extended in the present
      work to previously reported relationships between antiresorptive therapies and
      observed changes in DXA-derived BMD. These findings strongly indicate that
      critical and insightful reassessments of diagnostic/prognostic imputations
      underpinned by DXA in vivo BMD measurements are warranted. It is suggested that a
      good deal of what is known of bone fragility, bone densitometry, antiresorptive
      drug efficacy, and/or other therapeutic regimens, if based on patient-specific in
      vivo DXA methodology, may prove to be equivocal and tenuous.

PMID- 11344056
TI  - How many patients are needed? Variation and design considerations in bone
      histomorphometry.
AB  - In osteoporosis research, bone histomorphometry plays an important role in
      documenting the biological effects and possible side-effects of new drug
      treatments. To ensure that the study is properly scaled, it is important to be
      concerned with the risk of type II error; that is, the risk of failing to detect
      a real difference. We therefore calculated the necessary sample size in bone
      histomorphometric studies according to a specified difference of 15% between two
      groups. The calculations were based on variance components estimated from three
      different studies: women with a distal fracture of the forearm (n = 22); patients
      with pituitary insufficiency (n = 21); and patients with primary
      hyperparathyroidism (n = 21). Using a significance level of 0.05 and a risk of
      type II error of 0.20, the statistical power of two different designs was
      compared: a single biopsy design comparing the responses in two groups after the
      treatment; and a paired biopsy design in which individual differences
      (posttreatment minus baseline) were calculated before the comparison of the two
      groups. We found that the mineral apposition rate, wall thickness, and erosion
      depth are statistically powerful indices that, in the single biopsy design,
      require no more than n = 25 in each group to detect differences of 15% between
      the groups. Bone volume, erosion surface, osteoid surface, mineralizing surface,
      and activation frequency need group sizes of 100-600 individuals to find a 15%
      difference to be statistically significant. However, the effect of bisphosphonate
      treatment, for instance, is large enough to reduce the group size to 20
      individuals concerning activation frequency. The remodeling balance reaches
      extreme group sizes of several thousand for a 15% difference to be statistically
      significant, but for a 5 microm (approximately 150%) improvement, about 100
      individuals are required in the single biopsy design. An analysis of the
      components of variance showed that the variation between individuals is small and
      often negligible compared with the variation within individuals, and sample sizes
      needed for the paired biopsy design are therefore larger than those for the
      single biopsy design. In conclusion, the most cost-effective histomorphometric
      study design within a randomized clinical trial appears to be a single biopsy
      design comparing posttreatment biopsies with scaling performed according to the
      statistical power of the indices of interest.

PMID- 11344058
TI  - Clinically relevant frontal sinus anatomy and physiology.
AB  - Management of frontal sinus disease has evolved considerably with the advent of
      endoscopic paranasal sinus instrumentation. With this evolution has come the
      increased demand for anatomic competence among otolaryngologists. Armed with a
      better understanding of the complex frontal sinus and anterior ethmoid complex
      anatomy, the otolaryngologist can target the anatomic abnormalities that
      predispose an individual to frontal sinus disease and limit the effectiveness of
      medical and surgical management.

PMID- 11344057
TI  - Inhomogeneity of human vertebral cancellous bone: systematic density and
      structure patterns inside the vertebral body.
AB  - In the spine, cancellous bone quality is usually assessed for the whole vertebral
      body in a transverse central slice. Correct identification and assessment of the
      weakest parts of the cancellous bone may lead to better prediction of fracture
      risk. The density and structural parameters were systematically investigated
      inside the thoracic (T-9), thoracolumbar (T12-L1), and lumbar (L-4) vertebral
      bodies of nine subjects. On both sides of the median sagittal plane, anterior and
      posterior 8.2 mm vertical cores were harvested in the thoracic vertebra. In the
      thoracolumbar and lumbar vertebrae, external samples were also cored. Peripheral
      quantitative computed tomographic (pQCT) density analysis of the 136 cores was
      performed at four different levels, from the lower to the upper endplate. The
      relatively thin slice thickness (300 microm) and small pixel size (70 microm x 70
      microm) was considered sufficient to investigate the structural parameters on the
      four transverse slices and in the sagittal and coronal planes (total of 816
      images). Using a constant threshold a binary image was generated and the
      morphometric data were extracted. The binary image was further skeletonized and
      classical strut analysis was performed. Cancellous bone density was 20% higher in
      the posterior cores than in the anterior and external cores. Moreover, clear
      vertical inhomogeneity was noted because the lowest half of the vertebral body
      presented lower density than the upper half (differences ranging from 25% to
      15%). All structural parameters were strongly dependent on the location of the
      measurement. Structural differences between anterior, posterior, and external
      areas were mild and followed the density patterns. On the other hand, vertical
      inhomogeneity of the structural parameters was important. For example, in the
      thoracolumbar and lumbar vertebrae, the numbers of nodes or node-to-node struts
      were almost twofold higher in the inferior half than in the superior half (p <
      0.01), whereas trabecular thickness and number of free-ends presented a
      center/close-to-endplate structural pattern, with central trabeculae being 15%
      thicker (p < 0.05) and presenting 30% fewer free-ends (p < 0.01) than the close
      to-endplate ones. Variability of density and structural parameters was high and a
      substantial part of this variability could be explained by the place inside the
      vertebral body where the measurement was made. The weak part was not in the
      center of the body but in its upper half where the lower density did not seem to
      be compensated by a higher structural architecture. Further clinical
      investigation could enhance fracture prediction by tracking and focusing on the
      weakest part of the vertebral body.

PMID- 11344059
TI  - Imaging of frontal sinus disease: concepts, interpretation, and technology.
AB  - Imaging of the frontal sinus is an integral part of patient evaluation. High
      resolution computed tomography (CT) imaging is the preferred modality for
      evaluation of sinus inflammatory disease. Magnetic resonance (MR) imaging plays
      an important role in differentiating tumors from inflammatory diseases and serves
      as a problem-solving tool.

PMID- 11344060
TI  - Medical therapy of acute and chronic frontal rhinosinusitis.
AB  - Despite innovations in surgical treatment of frontal sinus disease, medical
      therapy continues to be important. Preoperative, perioperative, and postoperative
      considerations are discussed. Diagnostic criteria, microbiology, and
      complications associated with frontal rhinosinusitis are also reviewed.

PMID- 11344061
TI  - History of surgical approaches to the frontal sinus.
AB  - Despite the enormous number of external and endonasal surgical techniques
      described for the treatment of frontal sinus disease, a single time-proven
      technique has yet to be obtained. The purpose of this article is to critically
      evaluate the lessons of more than a century of endonasal and external procedures.
      The past has taught us a cautionary lesson for the surgical management of chronic
      frontal sinus disease, respect for the severity of iatrogenic disease caused by
      surgical trauma, and the need for long-term follow-up before embracing any new
      technique to treat this notoriously difficult clinical problem.

PMID- 11344062
TI  - Primary endoscopic management of the frontal sinus.
AB  - Surgical treatment of the frontal sinus continues to be an area of much interest
      and controversy. The complex anatomy and confined space of this region require
      the endoscopic surgeon to be knowledgeable and delicate to obtain a positive
      result. Proper instrumentation is crucial and continues to evolve over time.
      Postoperative endoscopic care is integral to the success of endoscopic frontal
      sinusotomy and the availability of proper office equipment to perform this care
      is critical. In most instances, the intranasal endoscopic approach can be
      accomplished successfully without the need for an external procedure.

PMID- 11344063
TI  - Revision endoscopic frontal sinus surgery.
AB  - Frontal sinusitis following functional endoscopic sinus surgery may represent
      persistent, recurrent, or iatrogenic disease. The narrow frontal recess is
      unforgiving of technical errors, and surgery within its confines requires ample
      training, skill, and patience. Revision surgery in this area, compromised by
      scarring and long-standing mucosal disease, demands even more of the endoscopic
      sinus surgeon. While successful treatment of this condition is a formidable task,
      strict attention to principles of proper medical and surgical therapy can
      increase the chances of a favorable outcome.

PMID- 11344064
TI  - Frontal sinus irrigation: indications, results, and complications.
AB  - Management, diagnosis, and surgical treatment of the frontal sinus pathology
      remain a challenge for the rhinologist. Since the introduction of endoscopic
      instrumentation, the frontal recess may be reached easily and a variety of
      endonasal approaches have been rediscovered. Although the endoscopic technique
      allows direct visualization and manipulation, some problems remain, from
      localization of the frontal sinus ostium during the procedure to the management
      of the postoperative care to prevent stenosis. The frontal irrigation is
      suggested as a useful adjunct during the endonasal approach to locate the frontal
      drainage.

PMID- 11344065
TI  - Frontal sinus stenting.
AB  - Recurrence of frontal sinusitis following external and endoscopic intranasal
      drainage procedures has been and is presently a challenge to rhinologic surgeons.
      The complexity of the anatomy, especially with regard to size of the newly
      created frontal neo-ostium, directly influences long-term success. Frontal sinus
      stenting is indicated if the neo-ostium is less than 5 mm. Other important
      factors include excessive denuded bone, remnants of osteitic bone in the frontal
      recess, and severe mucosal disease as seen in allergic fungal sinusitis and
      nonallergic eosinophilic rhinitis. Lateralization of the middle turbinate and
      excessive removal of the middle turbinate have also been associated with
      recurrent frontal sinus disease. This article reviews previous frontal sinus
      stenting techniques and introduces a new soft self-retaining frontal sinus stent
      designed for endoscopic insertion.

PMID- 11344066
TI  - Computer-aided frontal sinus surgery.
AB  - Computer-aided surgery technology supports computer-enabled review of CT images
      and intraoperative surgical anatomy. Many rhinologic surgeons have embraced
      computer-aided surgery for complicated frontal sinus procedures because computer
      aided surgery may simplify these complex procedures. This article discusses the
      fundamental principles of computer-aided surgery, its limitations, and its
      application to frontal sinus surgery.

PMID- 11344068
TI  - The modified Lothrop procedure: indications, results, and complications.
AB  - The modified Lothrop procedure or frontal sinus drill-out is a completely
      intranasal technique that creates a common frontonasal communication to allow
      drainage and ventilation of the chronically infected frontal sinus. It is an
      effective alternative to the classic frontal sinus obliteration. The modified
      Lothrop is usually performed on an outpatient basis, leaves no external scars,
      provides excellent visualization of the frontal sinus in the postoperative
      setting, and yields a high cure rate in chronically infected patients.

PMID- 11344067
TI  - Revision endoscopic frontal sinusotomy with mucoperiosteal flap advancement: the
      frontal sinus rescue procedure.
AB  - Frontal sinusitis after middle turbinate resection occurs because of stenosis of
      the frontal ostium by soft tissue scarring or residual bony fragments (which are
      pulled to the medial orbital wall by scar contracture). Standard endoscopic
      techniques cannot address this problem; however, revision endoscopic frontal
      sinusotomy with mucoperiosteal flap advancement (the frontal sinus rescue
      procedure) relieves this bony stenosis and incorporates a mucosal flap that
      minimizes postoperative stenosis.

PMID- 11344069
TI  - The five year experience with endoscopic trans-septal frontal sinusotomy.
AB  - Endoscopic trans-septal frontal sinusotomy (TSFS) represents a unique surgical
      approach to the floor of the frontal sinus. Although the final result can have
      similarities to the modified Lothrop procedure in that the intersinus septum may
      be drilled out, endoscopic TSFS represents a novel approach that can be valuable
      in patients with certain anatomic configurations. Endoscopic TSFS represents an
      alternate approach to the frontal sinus that may be used by the experienced
      endoscopist to augment treatment of refractory frontal sinus disease. This
      procedure is best considered for patients with favorable anatomy who have
      significant frontal sinus disease and cannot be managed adequately through an
      endoscopic frontal sinusotomy.

PMID- 11344070
TI  - Frontoethmoidectomy with Sewall-Boyden reconstruction: indications, technique,
      and philosophy.
AB  - The Sewall-Boyden flap, as used to reconstruct a frontal recess after
      frontoethmoidectomy, is conceptually similar to the endoscopic Lothrop procedure
      for surgical access to the frontal sinus. The operative technique, indications,
      and philosophy are presented in this article.

PMID- 11344071
TI  - State-of-the-art for osteoplastic frontal sinus operation.
AB  - Endoscopic ethmoid and frontal sinus surgery have reduced but not eliminated the
      indication for the osteoplastic adipose obliteration operation. An updated
      technique for this operation is presented for treating chronic frontal sinus
      disease, cerebrospinal fluid leakage by way of frontal sinus, and sinucutaneous
      fistulae.

PMID- 11344072
TI  - Hydroxyapatite: an alternative method of frontal sinus obliteration.
AB  - Obliteration of the frontal sinus may be necessary for the treatment of chronic
      sinusitis, infectious complications, trauma, and benign and malignant neoplasms.
      Hydroxyapatite cement (HAC) is a relatively new material that is approved for the
      repair of cranial defects. HAC has been successfully used to obliterate the
      frontal sinus in 19 patients with few minor complications and the avoidance of
      donor site morbidity. Compared with other alloplastic materials, HAC has the
      advantages of easy use, biocompatibility, and osseointegration.

PMID- 11344073
TI  - The frontal sinus unobliteration procedure.
AB  - Although intranasal frontal sinusotomy can now be performed for most cases of
      chronic frontal sinusitis, the osteoplastic frontal sinus procedure with
      obliteration, unfortunately, still is considered by many to be the standard for
      chronic frontal sinusitis against that which other frontal sinus procedures are
      judged. Unobliterating the previously obliterated sinus is indicated for patients
      with evidence of frontal sinus pathology on CT or MR images and for patients with
      chronic symptoms with equivocal radiologic results. The reopened frontal sinus
      can be reventilated and remucosalized, or reobliterated with the placement of a
      new fat graft. Complete or partial auto-obliteration by new bone formation or
      fibrosis is another possible endpoint that can result when unobliteration is
      attempted.

PMID- 11344075
TI  - Headache and the frontal sinus.
AB  - Frontal headache is a common complaint associated with frontal sinus disease and
      is often the only complaint. It is also a common location for headache pain in
      association with other primary and secondary headache disorders. Therefore, the
      clinician needs to have a thorough understanding of the differential diagnosis of
      frontal headache pain. This article reviews the causes of frontal pain in
      association with nasal and sinus pathology and also discusses other headache
      disorders that can present with similar symptoms.

PMID- 11344074
TI  - Complications of frontal sinusitis and their management.
AB  - Because of the anatomic location and venous drainage pattern of the frontal
      sinus, complications commonly involve intracranial structures but can involve the
      orbit and adjacent bony and soft tissue structures also. Evaluation of patients
      by a thorough history and physical examination, culture of purulent discharge or
      infected bone, and axial and coronal CT scanning with contrast is important for
      diagnosis and treatment planning. Treatment of complications uniformly involves
      the use of intravenous antibiotics and appropriate drainage procedures to arrest
      the infection and allow for resolution of the inflammatory complication.
      Significant morbidity and mortality from complications can occur despite
      aggressive medical and surgical treatment.

PMID- 11344076
TI  - Transnasal endoscopic management of frontal mucoceles.
AB  - Traditional teaching has emphasized the need for complete removal of sinus
      mucocele to achieve a cure. With the introduction of endoscopic sinus surgical
      instruments and techniques, however, there has been a trend toward transnasal
      endoscopic management of frontal mucoceles with recurrence rates at or close to
      0%. This article presents a useful classification of frontal mucoceles and the
      transnasal endoscopic surgical technique.

PMID- 11344077
TI  - Benign lesions of the frontal sinus.
AB  - Benign tumors of the frontal sinus including fibro-osseous lesions and inverted
      papillomata present unique problems for the rhinologist. Because of the bony
      cavity surrounding the frontal sinus and relatively small portal into the nose,
      conventional techniques including the osteoplastic flap, frontal trephination,
      and lynch procedure have provided useful approaches to these tumors. The advent
      of endoscopic techniques in the management of chronic inflammatory disease of the
      paranasal and, specifically, frontal sinuses, has led to these traditional
      techniques being augmented successfully, and, in some cases, surpassed by newer
      endoscopic techniques. This article reviews the diagnosis and management of the
      two most common types of benign tumors of the frontal sinus, bony tumors and
      inverted papillomata, with emphasis on the usefulness of the endoscope in
      managing such lesions.

PMID- 11344078
TI  - Frontal sinus malignancies.
AB  - Frontal sinus malignancies comprise 2% to 3% of those occurring in the paranasal
      region. Patients commonly present with forehead pain and swelling, orbital
      disturbances, epistaxis, and nasal purulence. A combination of CT and MR imaging
      delineate the tumor and its relationship with the adjacent dura and periorbita.
      Low-grade malignancies are addressed with en bloc extirpation, with lower frontal
      sinus and adjacent ethmoid lesions approached through a superior rhinotomy, and
      more extensive lesions through a combination of a bicoronal flap and rhinotomy.
      Postoperative irradiation is appropriate for medium- to high-grade lesions. Small
      to medium defects are closed with local rotation flaps and larger defects with
      free flaps. Bony reconstruction can range from a split calvarial bone graft to
      mini plates and wire mesh.

PMID- 11344080
TI  - Roles of the heat shock transcription factors in regulation of the heat shock
      response and beyond.
AB  - The heat shock response, characterized by increased expression of heat shock
      proteins (Hsps) is induced by exposure of cells and tissues to extreme conditions
      that cause acute or chronic stress. Hsps function as molecular chaperones in
      regulating cellular homeostasis and promoting survival. If the stress is too
      severe, a signal that leads to programmed cell death, apoptosis, is activated,
      thereby providing a finely tuned balance between survival and death. In addition
      to extracellular stimuli, several nonstressful conditions induce Hsps during
      normal cellular growth and development. The enhanced heat shock gene expression
      in response to various stimuli is regulated by heat shock transcription factors
      (HSFs). After the discovery of the family of HSFs (i.e., murine and human HSF1,
      2, and 4 and a unique avian HSF3), the functional relevance of distinct HSFs is
      now emerging. HSF1, an HSF prototype, and HSF3 are responsible for heat-induced
      Hsp expression, whereas HSF2 is refractory to classical stressors. HSF4 is
      expressed in a tissue-specific manner; similar to HSF1 and HSF2, alternatively
      spliced isoforms add further complexity to its regulation. Recently developed
      powerful genetic models have provided evidence for both cooperative and specific
      functions of HSFs that expand beyond the heat shock response. Certain specialized
      functions of HSFs may even include regulation of novel target genes in response
      to distinct stimuli.

PMID- 11344081
TI  - The ataxia-telangiectasia gene product may modulate DNA turnover and control cell
      fate by regulating cellular redox in lymphocytes.
AB  - The ATM kinase, when activated postnatally, exerts multiple functions to prevent
      the onset of ataxia-telangiectasia (AT). Using freshly isolated thymocytes from
      Atm-/- mice that were under stress during postnatal differentiation, we noted
      that thiol redox activity, as indicated by reduction of the tetrazolium MTS, and
      DNA turnover activity, as indicated by incorporation of [(3)H]thymidine into DNA,
      were both greatly increased compared with activities in thymocytes from Atm+/+
      mice. This increased thymidine incorporation could be suppressed by the thiol N
      acetylcysteine. In primary noncycling splenocytes, mitogens proportionally
      increased both the rate of [(3)H]thymidine incorporation and the rate of
      reduction of MTS. The mitogen-induced activities in splenocytes were not affected
      by ATM but were suppressed by the calcineurin-dependent inhibitor FK-506, which
      has no effect on these activities in thymocytes. These findings suggest that
      increased [(3)H]thymidine incorporation and reducing power indicate increased
      cell cycling in mitogenically stimulated splenocytes, whereas these two
      indicators represent increased FK-506-independent DNA turnover activities in
      thymocytes. Thus, a primary function of ATM is to activate the redox-sensitive
      checkpoint required for down-regulation of DNA turnover activities in developing
      lymphocytes. Cell-cycling checkpoints in undamaged quiescent lymphocytes are not
      activated by ATM with mitogenic stimulation. ATM may suppress abnormal DNA
      turnover and the resultant oncogenesis by regulating cellular thiol redox
      pathways.

PMID- 11344082
TI  - Extracellular ADP is a powerful osteolytic agent: evidence for signaling through
      the P2Y(1) receptor on bone cells.
AB  - There is increasing evidence that extracellular nucleotides act on bone cells via
      P2 receptors. This study investigated the action of ADP and 2-methylthioADP, a
      potent ADP analog with selectivity for the P2Y(1) receptor, on osteoclasts, the
      bone-resorbing multinuclear cells. Using three different assays, we show that ADP
      and 2-methylthioADP at nanomolar to submicromolar levels caused up to fourfold to
      sixfold increases in osteoclastic bone resorption. On mature rat osteoclasts,
      cultured for 1 day on polished dentine disks, peak effects on resorption pit
      formation were observed between 20 nM and 2 microM of ADP. The same
      concentrations of ADP also stimulated osteoclast and resorption pit formation in
      10-day mouse marrow cultures on dentine disks. In 3-day explant cultures of mouse
      calvarial bones, the stimulatory effect of ADP on osteoclast-mediated Ca(2+)
      release was greatest at 5-50 microM and equivalent to the maximal effects of
      prostaglandin E(2). The ADP effects were blocked in a nontoxic manner by MRS
      2179, a P2Y(1) receptor antagonist. Using in situ hybridization and
      immunocytochemistry, we found evidence for P2Y(1) receptor expression on both
      osteoclasts and osteoblasts; thus, ADP could exert its actions both directly on
      osteoclasts and indirectly via P2Y(1) receptors on osteoblasts. As a major ATP
      degradation product, ADP is a novel stimulator of bone resorption that could help
      mediate inflammatory bone loss in vivo.

PMID- 11344083
TI  - Direct viewing of atherosclerosis in vivo: plaque invasion by leukocytes is
      initiated by the endothelial selectins.
AB  - Leukocyte infiltration in atherosclerosis has been extensively investigated by
      using histological techniques on fixed tissues. In this study, intravital
      microscopic observations of leukocyte recruitment in the aorta of atherosclerotic
      mice were performed. Interactions between leukocytes and atherosclerotic
      endothelium were highly transient, thereby limiting the ability for rolling
      leukocytes to firmly adhere. Leukocyte rolling was abolished by function
      inhibition of P-selectin (P<0.001, n=8), whereas antibody blockage of E-selectin
      (n=10) decreased rolling leukocyte flux to 51 +/- 9.9% (mean+/-SE, P<0.01) and
      increased leukocyte rolling velocity to 162 +/- 18% (P<0.01) of pretreatment
      values. Notably, function inhibition of the integrin alpha(4) subunit (n=5) had
      no effect on rolling flux (107+/-25%, P=0.782) or rolling velocity (89+/-6.1%,
      P=0.147), despite endothelial expression of vascular cell adhesion molecule 1
      (VCAM-1). Leukocytes interacting with atherosclerotic endothelium were
      predominantly neutrophils, because treatment with antineutrophil serum decreased
      rolling and neutrophil counts in peripheral blood to the same extent. In
      conclusion, we present the first direct observations of atherosclerosis in vivo.
      We show that transient dynamics of leukocyte-endothelium interactions are
      important regulators of arterial leukocyte recruitment and that leukocyte rolling
      in atherosclerosis is critically dependent on the endothelial selectins. This
      experimental technique and the data presented introduce a novel perspective for
      the study of pathophysiological events involved in large-vessel disease.

PMID- 11344084
TI  - Heme oxygenase expression in human placenta and placental bed: reduced expression
      of placenta endothelial HO-2 in preeclampsia and fetal growth restriction.
AB  - In this study we tested the hypothesis that expression of heme oxygenases HO-1
      and HO-2, which are responsible for the production of carbon monoxide, are
      reduced in the placenta and placental bed of pregnancies complicated by
      preeclampsia (PE) and fetal growth restriction (FGR) compared with control third
      trimester pregnancies. Placental protein expression was determined by Western
      blotting (n=10 in each group) and immunohistochemistry (controls n=18, PE n=19,
      FGR n=10). Extravillous trophoblast expression was determined by
      immunohistochemistry of placental bed biopsy samples (controls n=17, PE n=19, FGR
      n=10). Western blot analysis of placental homogenates showed no overall
      differences in HO-2 among groups. However, immunohistochemical analysis showed a
      reduction in HO-2 expression in endothelial cells in both abnormal groups (PE
      P<0.01; FGR P<0.0005 vs. control group) but no differences in villous trophoblast
      staining. HO-1 was undetectable by Western blotting in control and abnormal
      pregnancies and immunoreactivity was very low, suggesting that there is little HO
      1 in the placenta. Within the placental bed, HO-2 but not HO-1 was detected on
      all populations of extravillous trophoblast, but expression of HO-2 or HO-1 did
      not change in PE or FGR. The reduced expression of HO-2 on endothelial cells in
      PE and FGR may be responsible for reduced placental blood flow in these
      conditions. The data do not show changes in HO in the placental bed in PE or FGR.

PMID- 11344085
TI  - Inflammatory cytokines inhibit myogenic differentiation through activation of
      nuclear factor-kappaB.
AB  - Muscle wasting is often associated with chronic inflammation. Because tumor
      necrosis factor alpha (TNF-alpha) has been implicated as a major mediator of
      cachexia, its effects on C2C12 myocytes were examined. TNF-alpha activated
      nuclear factor-kappaB (NF-kappaB) and interfered with the expression of muscle
      proteins in differentiating myoblasts. Introduction of a mutant form of
      inhibitory protein kappaBalpha (IkappaBalpha) restored myogenic differentiation
      in myoblasts treated with TNF-alpha or interleukin 1beta. Conversely, activation
      of NF-kappaB by overexpression of IkappaB kinase was sufficient to block
      myogenesis, illustrating the causal link between NF-kappaB activation and
      inhibition of myogenic differentiation. The inhibitory effects of TNF-alpha on
      myogenic differentiation were reversible, indicating that the effects of the
      cytokine were not due to nonspecific toxicity. Treatment of differentiated
      myotubes with TNF-alpha did not result in a striking loss of muscle-specific
      proteins, which shows that myogenesis was selectively affected in the myoblast
      stage by TNF-alpha. An important finding was that NF-kappaB was activated to the
      same extent in differentiating and differentiated cells, illustrating that once
      myocytes have differentiated they become refractory to the effects of NF-kappaB
      activation. These results demonstrate that inflammatory cytokines may contribute
      to muscle wasting through the inhibition of myogenic differentiation via a NF
      kappaB-dependent pathway.

PMID- 11344086
TI  - Acute hypoxia and hypoxic exercise induce DNA strand breaks and oxidative DNA
      damage in humans.
AB  - The present study investigated the effect of a single bout of exhaustive exercise
      on the generation of DNA strand breaks and oxidative DNA damage under normal
      conditions and at high-altitude hypoxia (4559 meters for 3 days). Twelve healthy
      subjects performed a maximal bicycle exercise test; lymphocytes were isolated for
      analysis of DNA strand breaks and oxidatively altered nucleotides, detected by
      endonuclease III and formamidipyridine glycosylase (FPG) enzymes. Urine was
      collected for 24 h periods for analysis of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8
      oxodG), a marker of oxidative DNA damage. Urinary excretion of 8-oxodG increased
      during the first day in altitude hypoxia, and there were more endonuclease III
      sensitive sites on day 3 at high altitude. The subjects had more DNA strand
      breaks in altitude hypoxia than at sea level. The level of DNA strand breaks
      further increased immediately after exercise in altitude hypoxia. Exercise
      induced generation of DNA strand breaks was not seen at sea level. In both
      environments, the level of FPG and endonuclease III-sensitive sites remained
      unchanged immediately after exercise. DNA strand breaks and oxidative DNA damage
      are probably produced by reactive oxygen species, generated by leakage of the
      mitochondrial respiration or during a hypoxia-induced inflammation. Furthermore,
      the presence of DNA strand breaks may play an important role in maintaining
      hypoxia-induced inflammation processes. Hypoxia seems to deplete the antioxidant
      system of its capacity to withstand oxidative stress produced by exhaustive
      exercise.

PMID- 11344087
TI  - Protective effects of n-acetylcysteine on lung injury and red blood cell
      modification induced by carrageenan in the rat.
AB  - Oxidative stress has been suggested as a potential mechanism in the pathogenesis
      of lung inflammation. The pharmacological profile of n-acetylcysteine (NAC), a
      free radical scavenger, was evaluated in an experimental model of lung injury
      (carrageenan-induced pleurisy). Injection of carrageenan into the pleural cavity
      of rats elicited an acute inflammatory response characterized by fluid
      accumulation in the pleural cavity that contained many neutrophils (PMNs), an
      infiltration of PMNs in lung tissues and subsequent lipid peroxidation, and
      increased production of nitrite/nitrate, tumor necrosis factor alpha, and
      interleukin 1beta. All parameters of inflammation were attenuated by NAC
      treatment. Furthermore, carrageenan induced an up-regulation of the adhesion
      molecules ICAM-1 and P-selectin, as well as nitrotyrosine and poly (ADP-ribose)
      synthetase (PARS), as determined by immunohistochemical analysis of lung tissues.
      The degree of staining for the ICAM-1, P-selectin, nitrotyrosine, and PARS was
      reduced by NAC. In vivo NAC treatment significantly reduced peroxynitrite
      formation as measured by the oxidation of the fluorescent dihydrorhodamine-123,
      prevented the appearance of DNA damage, an decrease in mitochondrial respiration,
      and partially restored the cellular level of NAD+ in ex vivo macrophages
      harvested from the pleural cavity of rats subjected to carrageenan-induced
      pleurisy. A significant alteration in the morphology of red blood cells was
      observed 24 h after carrageenan administration. NAC treatment has the ability to
      significantly diminish the red blood cell alteration. Our results clearly
      demonstrate that NAC treatment exerts a protective effect and clearly indicate
      that NAC offers a novel therapeutic approach for the management of lung injury
      where radicals have been postulated to play a role.

PMID- 11344088
TI  - Diversification of neurotoxins by C-tail 'wiggling': a scorpion recipe for
      survival.
AB  - The structure of bioactive surfaces of proteins is a subject of intensive
      research, yet the mechanisms by which such surfaces have evolved are largely
      unknown. Polypeptide toxins produced by venomous animals such as sea anemones,
      cone snails, scorpions, and snakes show multiple routes for active site
      diversification, each maintaining a typical conserved scaffold. Comparative
      analysis of an array of genetically related scorpion polypeptide toxins that
      modulate sodium channels in neuronal membranes suggests a unique route of toxic
      site diversification. This premise is based on recent identification of bioactive
      surfaces of toxin representative of three distinct pharmacological groups and a
      comparison of their 3-dimensional structures. Despite their similar scaffold, the
      bioactive surfaces of the various toxins vary considerably, but always coincide
      with the molecular exterior onto which the C-tail is anchored. Superposition of
      the toxin structures indicates that the C-tails diverge from a common structural
      start point, which suggests that the pharmacological versatility displayed by
      these toxins might have been achieved along evolution via structural
      reconfiguration of the C-tail, leading to reshaping of new bioactive surfaces.

PMID- 11344089
TI  - Possible role of uncoupling protein in regulation of myocardial energy metabolism
      in aortic regurgitation model rats.

PMID- 11344090
TI  - Targeted inactivation of the sodium-calcium exchanger (Ncx1) results in the lack
      of a heartbeat and abnormal myofibrillar organization.

PMID- 11344091
TI  - Sphingosine 1-phosphate modulates human airway smooth muscle cell functions that
      promote inflammation and airway remodeling in asthma.

PMID- 11344092
TI  - Nonvascular role for VEGF: VEGFR-1, 2 activity is critical for neural retinal
      development.

PMID- 11344093
TI  - Vascular endothelial growth factor rescues hippocampal neurons from glutamate
      induced toxicity: signal transduction cascades.

PMID- 11344094
TI  - Induction of CD36 by all-trans retinoic acid: retinoic acid receptor signaling in
      the pathogenesis of atherosclerosis.

PMID- 11344095
TI  - Werner syndrome cells are sensitive to DNA cross-linking drugs.

PMID- 11344096
TI  - Hypoxia reverses dibutyryl-cAMP-induced stellation of cultured astrocytes via
      activation of the endothelin system.

PMID- 11344097
TI  - Synergism between platelets and leukocytes in inducing endothelial cell apoptosis
      in the cold ischemic rat liver: a Kupffer cell-mediated injury.

PMID- 11344098
TI  - Induction of plasminogen activator inhibitor 1 gene expression in adipocytes by
      thiazolidinediones.

PMID- 11344099
TI  - Identification of a specific sperm nuclei selenoenzyme necessary for protamine
      thiol cross-linking during sperm maturation.

PMID- 11344100
TI  - Induction of VEGF in perivascular cells defines a potential paracrine mechanism
      for endothelial cell survival.

PMID- 11344101
TI  - Altered intracellular processing and release of neuropeptide Y due to leucine 7
      to proline 7 polymorphism in the signal peptide of preproneuropeptide Y in
      humans.

PMID- 11344102
TI  - Aberrant amplification of A(2A) receptor signaling in striatal cells expressing
      mutant huntingtin.

PMID- 11344103
TI  - Hepatocyte growth factor induces MAT2A expression and histone acetylation in rat
      hepatocytes: role in liver regeneration.

PMID- 11344104
TI  - Expression of the glaucoma gene myocilin (MYOC) in the human optic nerve head.

PMID- 11344105
TI  - The isoprostane 8-iso-PGF(2alpha) stimulates endothelial cells to bind monocytes:
      differences from thromboxane-mediated endothelial activation.

PMID- 11344106
TI  - PECAM-1 (CD31) engagement activates a phosphoinositide-independent, nonspecific
      cation channel in endothelial cells.

PMID- 11344107
TI  - Hepatic mRNAs up-regulated by starvation: an expression profile determined by
      suppression subtractive hybridization.

PMID- 11344108
TI  - Constitutive expression of arginase in microvascular endothelial cells
      counteracts nitric oxide-mediated vasodilatory function.

PMID- 11344109
TI  - Hypoxia promotes oxidative base modifications in the pulmonary artery endothelial
      cell VEGF gene.

PMID- 11344110
TI  - Astrocytes of the mouse neocortex express functional N-methyl-D-aspartate
      receptors.

PMID- 11344111
TI  - Aspirin-induced activation of the NF-kappaB signaling pathway: a novel mechanism
      for aspirin-mediated apoptosis in colon cancer cells.

PMID- 11344112
TI  - HFE inhibits apical iron uptake by intestinal epithelial (Caco-2) cells.

PMID- 11344113
TI  - Space shuttle flight (STS-90) enhances degradation of rat myosin heavy chain in
      association with activation of ubiquitin-proteasome pathway.

PMID- 11344114
TI  - Muscle loading modulates aquaporin-4 expression in skeletal muscle.

PMID- 11344115
TI  - Modeling of risk factors for the degeneration of retinal ganglion cells after
      ischemia/reperfusion in rats: effects of age, caloric restriction, diabetes,
      pigmentation, and glaucoma.

PMID- 11344116
TI  - Dystonia and cerebellar atrophy in Cacna1a null mice lacking P/Q calcium channel
      activity.

PMID- 11344117
TI  - Formation of peroxynitrite in vascular endothelial cells exposed to cyclosporine
      A.

PMID- 11344118
TI  - Recombinant Sendai virus-mediated gene transfer to vasculature: a new class of
      efficient gene transfer vector to the vascular system.

PMID- 11344119
TI  - Inhibition of Alzheimer's disease beta-amyloid aggregation, neurotoxicity, and in
      vivo deposition by nitrophenols: implications for Alzheimer's therapy.

PMID- 11344120
TI  - Development of growth factor fusion proteins for cell-triggered drug delivery.

PMID- 11344121
TI  - Nitric oxide selectively releases metals from the amino-terminal domain of
      metallothioneins: potential role at inflammatory sites.

PMID- 11344122
TI  - Intravesical oncolytic viral therapy using attenuated, replication-competent
      herpes simplex viruses G207 and Nv1020 is effective in the treatment of bladder
      cancer in an orthotopic syngeneic model.

PMID- 11344123
TI  - Anti-interferon gamma action of epigallocatechin-3-gallate mediated by specific
      inhibition of STAT1 activation.

PMID- 11344124
TI  - Induction of HIF-1alpha in response to hypoxia is instantaneous.

PMID- 11344125
TI  - Changes in cytosolic and membrane TNF inhibitory protein-B1 (TIP-B1) levels
      associated with protection from TNF-induced cytotoxicity.

PMID- 11344126
TI  - Endotoxins induce and interferon alpha suppresses vascular endothelial growth
      factor (VEGF) production in human peripheral blood mononuclear cells.

PMID- 11344127
TI  - Identification of two novel, kinase-deficient variants of discoidin domain
      receptor 1: differential expression in human colon cancer cell lines.

PMID- 11344128
TI  - Dexfenfluramine as a mitogen signal via the formation of superoxide anion.

PMID- 11344129
TI  - A dimeric two-component receiver domain inhibits the sigma54-dependent ATPase in
      DctD.

PMID- 11344130
TI  - Apolipoprotein D interacts with the long-form leptin receptor: a hypothalamic
      function in the control of energy homeostasis.

PMID- 11344131
TI  - Latrophilin-like receptor from the parasitic nematode Haemonchus contortus as
      target for the anthelmintic depsipeptide PF1022A.

PMID- 11344133
TI  - Structural and functional analysis of the phosphonoacetate hydrolase (phnA) gene
      region in Pseudomonas fluorescens 23F.
AB  - The Pseudomonas fluorescens 23F phosphonoacetate hydrolase gene (phnA) encodes a
      novel carbon-phosphorus bond cleavage enzyme whose expression is independent of
      the phosphate status of the cell. Analysis of the regions adjacent to the
      phosphonoacetate hydrolase structural gene (phnA) indicated the presence of five
      open reading frames (ORFs). These include one (phnR) whose putative product shows
      high levels of homology to the LysR family of positive transcriptional
      regulators. Its presence was shown to be necessary for induction of the hydrolase
      activity. 2-Phosphonopropionate was found to be an inducer (and poor substrate)
      for phosphonoacetate hydrolase. Unlike phosphonoacetate, which is also an inducer
      of phosphonoacetate hydrolase, entry of 2-phosphonopropionate into cells appeared
      to be dependent on the presence of a gene (phnB) that lies immediately downstream
      of phnA and whose putative product shows homology to the glycerol-3-phosphate
      transporter. RNA analysis revealed transcripts for the phnAB and phnR operons,
      which are transcribed divergently; the resulting mRNAs overlapped by 29
      nucleotide bases at their 5' ends. Transcripts of phnAB were detected only in
      cells grown in the presence of phosphonoacetate, whereas transcripts of phnR were
      observed in cells grown under both induced and uninduced conditions. The
      expression of three additional genes found in the phnA region did not appear
      necessary for the degradation of phosphonoacetate and 2-phosphonopropionate by
      either Pseudomonas putida or Escherichia coli cells.

PMID- 11344132
TI  - Polarity in action: asymmetric protein localization in bacteria.

PMID- 11344134
TI  - Characterization of a three-component vanillate O-demethylase from Moorella
      thermoacetica.
AB  - The Moorella thermoacetica aromatic O-demethylase was characterized as an
      inducible three-component system with similarity to the methanogenic methanol,
      methylamine, and methanethiol methyltransferases and to the O-demethylase system
      from Acetobacterium dehalogenans. MtvB catalyzes methyl transfer from a
      phenylmethylether to the cobalt center of MtvC, a corrinoid protein. MtvA
      catalyzes transmethylation from MtvC to tetrahydrofolate, forming
      methyltetrahydrofolate. Cobalamin can substitute for MtvC.

PMID- 11344135
TI  - Characterization and mutational analysis of three allelic lsc genes encoding
      levansucrase in Pseudomonas syringae.
AB  - In the plant pathogen Pseudomonas syringae pv. glycinea PG4180 and other
      bacterial species, synthesis of the exopolysaccharide levan is catalyzed by the
      extracellular enzyme levansucrase. The results of Southern blotting and PCR
      analysis indicated the presence of three levansucrase-encoding genes in strain
      PG4180: lscA, lscB, and lscC. In this study, lscB and lscC were cloned from a
      genomic library of strain PG4180. Sequence analysis of the two lsc genes showed
      that they were virtually identical to each other and highly similar to the
      previously characterized lscA gene. lscA and lscC had a chromosomal location,
      whereas lscB resided on an indigenous plasmid of PG4180. Mutants with impaired
      expression of individual lsc genes and double mutants were generated by marker
      exchange mutagenesis. Determination of levansucrase activities in these mutants
      revealed that the lscB gene product was secreted but not that of lscA or lscC.
      Our results indicated that lscB and lscC but not lscA contributed to periplasmic
      levan synthesis of PG4180. The lscB lscC double mutant was completely defective
      in levan formation and could be complemented by either lscB or lscC. Our data
      suggested a compartment-specific localization of two lsc gene products, with LscB
      being the secreted, extracellular enzyme and LscC being the predominantly
      periplasmic levansucrase. Results of Western blot analyses indicated that lscA
      was not expressed and that lscA was not associated with levansucrase activities
      in any particular protein fraction. LscA could be detected in PG4180 only when
      transcribed from the vector-borne P(lac) promoter. PCR screening in various P.
      syringae strains with primers derived from the three characterized lsc genes
      demonstrated the presence of multiple Lsc isoenzymes in other P. syringae
      pathovars.

PMID- 11344136
TI  - Functional analysis of 14 genes that constitute the purine catabolic pathway in
      Bacillus subtilis and evidence for a novel regulon controlled by the PucR
      transcription activator.
AB  - The soil bacterium Bacillus subtilis has developed a highly controlled system for
      the utilization of a diverse array of low-molecular-weight compounds as a
      nitrogen source when the preferred nitrogen sources, e.g., glutamate plus
      ammonia, are exhausted. We have identified such a system for the utilization of
      purines as nitrogen source in B. subtilis. Based on growth studies of strains
      with knockout mutations in genes, complemented with enzyme analysis, we could
      ascribe functions to 14 genes encoding enzymes or proteins of the purine
      degradation pathway. A functional xanthine dehydrogenase requires expression of
      five genes (pucA, pucB, pucC, pucD, and pucE). Uricase activity is encoded by the
      pucL and pucM genes, and a uric acid transport system is encoded by pucJ and
      pucK. Allantoinase is encoded by the pucH gene, and allantoin permease is encoded
      by the pucI gene. Allantoate amidohydrolase is encoded by pucF. In a pucR mutant,
      the level of expression was low for all genes tested, indicating that PucR is a
      positive regulator of puc gene expression. All 14 genes except pucI are located
      in a gene cluster at 284 to 285 degrees on the chromosome and are contained in
      six transcription units, which are expressed when cells are grown with glutamate
      as the nitrogen source (limiting conditions), but not when grown on glutamate
      plus ammonia (excess conditions). Our data suggest that the 14 genes and the gde
      gene, encoding guanine deaminase, constitute a regulon controlled by the pucR
      gene product. Allantoic acid, allantoin, and uric acid were all found to function
      as effector molecules for PucR-dependent regulation of puc gene expression. When
      cells were grown in the presence of glutamate plus allantoin, a 3- to 10-fold
      increase in expression was seen for most of the genes. However, expression of the
      pucABCDE unit was decreased 16-fold, while expression of pucR was decreased 4
      fold in the presence of allantoin. We have identified genes of the purine
      degradation pathway in B. subtilis and showed that their expression is subject to
      both general nitrogen catabolite control and pathway-specific control.

PMID- 11344137
TI  - Isolation of a new broad-host-range IncQ-like plasmid, pTC-F14, from the
      acidophilic bacterium Acidithiobacillus caldus and analysis of the plasmid
      replicon.
AB  - A moderately thermophilic (45 to 50 degrees C), highly acidophilic (pH 1.5 to
      2.5), chemolithotrophic Acidithiobacillus caldus strain, f, was isolated from a
      biooxidation process used to treat nickel ore. Trans-alternating field
      electrophoresis analysis of total DNA from the A. caldus cells revealed two
      plasmids of approximately 14 and 45 kb. The 14-kb plasmid, designated pTC-F14,
      was cloned and shown by replacement of the cloning vector with a kanamycin
      resistance gene to be capable of autonomous replication in Escherichia coli.
      Autonomous replication was also demonstrated in Pseudomonas putida and
      Agrobacterium tumefaciens LBA 4404, which suggested that pTC-F14 is a broad-host
      range plasmid. Sequence analysis of the pTC-F14 replicon region revealed five
      open reading frames and a replicon organization like that of the broad-host-range
      IncQ plasmids. Three of the open reading frames encoded replication proteins
      which were most closely related to those of IncQ-like plasmid pTF-FC2 (amino acid
      sequence identities: RepA, 81%; RepB, 78%; RepC, 74%). However, the two plasmids
      were fully compatible and pTC-F14 represents a new IncQ-like plasmid replicon.
      Surprisingly, asymmetrical incompatibility was found with the less closely
      related IncQ plasmid R300B derivative pKE462 and the IncQ-like plasmid derivative
      pIE1108. Analysis of the pTC-F14 oriV region revealed five direct repeats
      consisting of three perfectly conserved 22-bp iterons flanked by iterons of 23
      and 21 bp. Plasmid pTC-F14 had a copy number of 12 to 16 copies per chromosome in
      both E. coli, and A. caldus. The rep gene products of pTC-F14 and pTF-FC2 were
      unable to functionally complement each other's oriV regions, but replication
      occurred when the genes for each plasmid's own RepA, RepB, and RepC proteins were
      provided in trans. Two smaller open reading frames were found between the repB
      and repA genes of pTC-F14, which encode proteins with high amino acid sequence
      identity (PasA, 81%; PasB, 72%) to the plasmid addiction system of pTF-FC2. This
      is the second time a plasmid stability system of this type has been found on an
      IncQ-like plasmid.

PMID- 11344138
TI  - ChvD, a chromosomally encoded ATP-binding cassette transporter-homologous protein
      involved in regulation of virulence gene expression in Agrobacterium tumefaciens.
AB  - A yeast two-hybrid screen searching for chromosomally encoded proteins that
      interact with the Agrobacterium tumefaciens VirB8 protein was carried out. This
      screen identified an interaction candidate homologous to the partial sequence of
      a gene that had previously been identified in a transposon screen as a potential
      regulator of virG expression, chvD. In this report, the cloning of the entire
      chvD gene is described and the gene is sequenced and characterized. Insertion of
      a promoterless lacZ gene into the chvD locus greatly attenuated virulence and vir
      gene expression. Compared to that of the wild-type strain, growth of the chvD
      mutant was reduced in rich, but not minimal, medium. Expression of chvD, as
      monitored by expression of beta-galactosidase activity from the chvD-lacZ fusion,
      occurred in both rich and minimal media as well as under conditions that induce
      virulence gene expression. The ChvD protein is highly homologous to a family of
      ATP-binding cassette transporters involved in antibiotic export from bacteria and
      has two complete Walker box motifs. Molecular genetic analysis demonstrated that
      disruption of either Walker A box, singly, does not inactivate this protein's
      effect on virulence but that mutations in both Walker A boxes renders it
      incapable of complementing a chvD mutant strain. Constitutive expression of virG
      in the chvD mutant strain restored virulence, supporting the hypothesis that ChvD
      controls virulence through effects on virG expression.

PMID- 11344139
TI  - Functional analysis of the galactosyltransferases required for biosynthesis of D
      galactan I, a component of the lipopolysaccharide O1 antigen of Klebsiella
      pneumoniae.
AB  - D-Galactan I is an O-antigenic polymer with the repeat unit structure [-->3)-beta
      D-Galf-(1-->3)-alpha-D-Galp-(1-->], that is found in the lipopolysaccharide of
      Klebsiella pneumoniae O1 and other gram-negative bacteria. A genetic locus
      containing six genes is responsible for the synthesis and assembly of D-galactan
      I via an ATP-binding cassette (ABC) transporter-dependent pathway. The
      galactosyltransferase activities that are required for the processive
      polymerization of D-galactan I were identified by using in vitro reactions. The
      activities were determined with endogenous lipid acceptors in membrane
      preparations from Escherichia coli K-12 expressing individual enzymes (or
      combinations of enzymes) or in membranes reconstituted with specific lipid
      acceptors. The D-galactan I polymer is built on a lipid acceptor, undecaprenyl
      pyrophosphoryl-GlcpNAc, a product of the WecA enzyme that participates in the
      biosynthesis of enterobacterial common antigen and O-antigenic polysaccharide (O
      PS) biosynthesis pathways. This intermediate is directed into D-galactan I
      biosynthesis by the bifunctional wbbO gene product, which sequentially adds one
      Galp and one Galf residue from the corresponding UDP-sugars to form a lipid
      linked trisaccharide. The two galactosyltransferase activities of WbbO are
      separable by limiting the UDP-Galf precursor. Galactosyltransferase activity in
      membranes reconstituted with exogenous lipid-linked trisaccharide acceptor and
      the known structure of D-galactan I indicate that WbbM catalyzes the subsequent
      transfer of a single Galp residue to form a lipid-linked tetrasaccharide. Chain
      extension of the D-galactan I polymer requires WbbM for Galp transferase,
      together with Galf transferase activity provided by WbbO. Comparison of the
      biosynthetic pathways for D-galactan I and the polymannose E. coli O9a antigen
      reveals some interesting features that may reflect a common theme in ABC
      transporter-dependent O-PS assembly systems.

PMID- 11344140
TI  - Mu and IS1 transpositions exhibit strong orientation bias at the Escherichia coli
      bgl locus.
AB  - The region upstream of the Escherichia coli bgl operon is an insertion hot spot
      for several transposons. Elements as distantly related as Tn1, Tn5, and phage Mu
      home in on this location. To see what characteristics result in a high-affinity
      site for transposition, we compared in vivo and in vitro Mu transposition
      patterns near the bgl promoter. In vivo, Mu insertions were focused in two narrow
      zones of DNA near bgl, and both zones exhibited a striking orientation bias. Five
      hot spots upstream of the bgl cyclic AMP binding protein (CAP) binding site had
      Mu insertions exclusively with the phage oriented left to right relative to the
      direction of bgl transcription. One hot spot within the CAP binding domain had
      the opposite (right-to-left) orientation of phage insertion. The DNA segment
      lying between these two Mu hot-spot clusters is extremely A/T rich (80%) and is
      an efficient target for insertion sequences during stationary phase. IS1
      insertions that activate the bgl operon resulted in a decrease in Mu insertions
      near the CAP binding site. Mu transposition in vitro differed significantly from
      the in vivo transposition pattern, having a new hot-spot cluster at the border of
      the A/T-rich segment. Transposon hot-spot behavior and orientation bias may
      relate to an asymmetry of transposon DNA-protein complexes and to interactions
      with proteins that produce transcriptionally silenced chromatin.

PMID- 11344141
TI  - Reverse genetics of Escherichia coli glycerol kinase allosteric regulation and
      glucose control of glycerol utilization in vivo.
AB  - Reverse genetics is used to evaluate the roles in vivo of allosteric regulation
      of Escherichia coli glycerol kinase by the glucose-specific phosphocarrier of the
      phosphoenolpyruvate:glycose phosphotransferase system, IIA(Glc) (formerly known
      as III(glc)), and by fructose 1,6-bisphosphate. Roles have been postulated for
      these allosteric effectors in glucose control of both glycerol utilization and
      expression of the glpK gene. Genetics methods based on homologous recombination
      are used to place glpK alleles with known specific mutations into the chromosomal
      context of the glpK gene in three different genetic backgrounds. The alleles
      encode glycerol kinases with normal catalytic properties and specific alterations
      of allosteric regulatory properties, as determined by in vitro characterization
      of the purified enzymes. The E. coli strains with these alleles display the
      glycerol kinase regulatory phenotypes that are expected on the basis of the in
      vitro characterizations. Strains with different glpR alleles are used to assess
      the relationships between allosteric regulation of glycerol kinase and specific
      repression in glucose control of the expression of the glpK gene. Results of
      these studies show that glucose control of glycerol utilization and glycerol
      kinase expression is not affected by the loss of IIA(Glc) inhibition of glycerol
      kinase. In contrast, fructose 1,6-bisphosphate inhibition of glycerol kinase is
      the dominant allosteric control mechanism, and glucose is unable to control
      glycerol utilization in its absence. Specific repression is not required for
      glucose control of glycerol utilization, and the relative roles of various
      mechanisms for glucose control (catabolite repression, specific repression, and
      inducer exclusion) are different for glycerol utilization than for lactose
      utilization.

PMID- 11344142
TI  - Adenylate kinase as a virulence factor of Pseudomonas aeruginosa.
AB  - Adenylate kinase (AK; ATP:AMP phosphotransferase, EC 2.7.4.3) is a ubiquitous
      enzyme that contributes to the homeostasis of adenine nucleotides in eukaryotic
      and prokaryotic cells. AK catalyzes the reversible reaction Mg. ATP + AMP <-->
      Mg. ADP + ADP. In this study we show that AK secreted by the pathogenic strains
      of Pseudomonas aeruginosa appears to play an important role in macrophage cell
      death. We purified and characterized AK from the growth medium of a cystic
      fibrosis isolate strain of P. aeruginosa 8821 and hyperproduced it as a fusion
      protein with glutathione S-transferase. We demonstrated enhanced macrophage cell
      death in the presence of both the secreted and recombinant purified AK and its
      substrates AMP plus ATP or ADP. These data suggested that AK converts its
      substrates to a mixture of AMP, ADP, and ATP, which are potentially more
      cytotoxic than ATP alone. In addition, we observed increased macrophage killing
      in the presence of AK and ATP alone. Since the presence of ATPase activity on the
      macrophages was confirmed in the present work, external macrophage-effluxed ATP
      is converted to ADP, which in turn can be transformed by AK into a cytotoxic
      mixture of three adenine nucleotides. Evidence is presented in this study that
      secreted AK was detected in macrophages during infection with P. aeruginosa.
      Thus, the possible role of secreted AK as a virulence factor is in producing and
      keeping an intact pool of toxic mixtures of AMP, ADP, and ATP, which allows P.
      aeruginosa to exert its full virulence.

PMID- 11344143
TI  - Combined, functional genomic-biochemical approach to intermediary metabolism:
      interaction of acivicin, a glutamine amidotransferase inhibitor, with Escherichia
      coli K-12.
AB  - Acivicin, a modified amino acid natural product, is a glutamine analog. Thus, it
      might interfere with metabolism by hindering glutamine transport, formation, or
      usage in processes such as transamidation and translation. This molecule
      prevented the growth of Escherichia coli in minimal medium unless the medium was
      supplemented with a purine or histidine, suggesting that the HisHF enzyme, a
      glutamine amidotransferase, was the target of acivicin action. This enzyme,
      purified from E. coli, was inhibited by low concentrations of acivicin. Acivicin
      inhibition was overcome by the presence of three distinct genetic regions when
      harbored on multicopy plasmids. Comprehensive transcript profiling using DNA
      microarrays indicated that histidine biosynthesis was the predominant process
      blocked by acivicin. The response to acivicin, however, was quite complex,
      suggesting that acivicin inhibition resonated through more than a single cellular
      process.

PMID- 11344144
TI  - Role of trehalose in growth at high temperature of Salmonella enterica serovar
      Typhimurium.
AB  - Moderate osmolality can stimulate bacterial growth at temperatures near the upper
      limit for growth. We investigated the mechanism by which high osmolality enhances
      the thermotolerance of Salmonella enterica serovar Typhimurium, by isolating
      bacteriophage MudI1734-induced insertion mutations that blocked the growth
      stimulatory effect of 0.2 M NaCl at 45 degrees C. One of these mutations proved
      to be in the seqA gene (a regulator of initiation of DNA synthesis). Because this
      gene is cotranscribed with pgm (which encodes phosphoglucomutase), it is likely
      to be polar on the expression of the pgm gene. Pgm catalyzes the conversion of
      glucose-6-phosphate to glucose-1-phosphate during growth on glucose, and
      therefore loss of Pgm results in a deficiency in a variety of cellular
      constituents derived from glucose-1-phosphate, including trehalose. To test the
      possibility that the growth defect of the seqA::MudI1734 mutant at high
      temperature in medium of high osmolality is due to the block in trehalose
      synthesis, we determined the effect of an otsA mutation, which inactivates the
      first step of the trehalose biosynthetic pathway. The otsA mutation caused a
      growth defect at 45 degrees C in minimal medium containing 0.2 M NaCl that was
      similar to that caused by the pgm mutation, but otsA did not affect growth rate
      in this medium at 37 degrees C. These results suggest that the growth defect of
      the seqA-pgm mutant at high temperature could be a consequence of the block in
      trehalose synthesis. We found that, in addition to the well-known osmotic
      control, there is a temperature-dependent control of trehalose synthesis such
      that, in medium containing 0.2 M NaCl, cells grown at 45 degrees C had a fivefold
      higher trehalose pool size than cells grown at 30 degrees C. Our observations
      that trehalose accumulation is thermoregulated and that mutations that block
      trehalose synthesis cause a growth defect at high temperature in media of high
      osmolality suggested that this disaccharide is crucial for growth at high
      temperature either for turgor maintenance or for protein stabilization.

PMID- 11344145
TI  - Characterization of fsr, a regulator controlling expression of gelatinase and
      serine protease in Enterococcus faecalis OG1RF.
AB  - We have previously identified a locus, fsr, a homologue of staphylococcal agr
      loci, which positively regulates the expression of gelatinase and serine protease
      (encoded by gelE and sprE, respectively) in Enterococcus faecalis OG1RF. The
      expression of the three genes in the fsr locus, fsrA, fsrB, and fsrC, appears to
      be autoregulated, and we have shown that mutants with insertion disruptions in
      each of these three genes were significantly attenuated in a mouse peritonitis
      model compared to the parent strain. In the present study, we showed that fsrB
      and fsrC are highly expressed in the postexponential growth phase and that their
      expression is cell density dependent. Reverse transcriptase PCR using primers
      covering the intergenic regions in the fsr/gelE loci confirmed that fsrB and
      fsrC, as well as gelE and sprE, are cotranscribed. We also showed, using a
      nonpolar fsrB deletion mutant, that fsrB, the homologue of agrB of staphylococci
      with unknown function, is required for the regulatory function of fsr. Primer
      extension and analysis of transcriptional fusions indicated the presence of
      promoters immediately upstream of fsrA, of fsrB, and of gelE and that the fsrB
      and gelE promoters are fsr dependent, while the fsrA promoter is an fsr
      independent weak constitutive promoter. Two conserved 7-bp direct repeats were
      found immediately upstream of the fsrB and gelE promoters, similar to the repeats
      found upstream of P2 and P3 promoters of the agr locus; deletions and mutations
      in the repeated sequences completely abolished the fsrB and gelE promoter
      activities, suggesting that the repeats are important for the regulatory function
      in the fsrB and gelE promoter regions.

PMID- 11344146
TI  - Isolation of PDX2, a second novel gene in the pyridoxine biosynthesis pathway of
      eukaryotes, archaebacteria, and a subset of eubacteria.
AB  - In this paper we describe the isolation of a second gene in the newly identified
      pyridoxine biosynthesis pathway of archaebacteria, some eubacteria, fungi, and
      plants. Although pyridoxine biosynthesis has been thoroughly examined in
      Escherichia coli, recent characterization of the Cercospora nicotianae
      biosynthesis gene PDX1 led to the discovery that most organisms contain a
      pyridoxine synthesis gene not found in E. coli. PDX2 was isolated by a degenerate
      primer strategy based on conserved sequences of a gene specific to PDX1
      containing organisms. The role of PDX2 in pyridoxine biosynthesis was confirmed
      by complementation of two C. nicotianae pyridoxine auxotrophs not mutant in PDX1.
      Also, targeted gene replacement of PDX2 in C. nicotianae results in pyridoxine
      auxotrophy. Comparable to PDX1, PDX2 homologues are not found in any of the
      organisms with homologues to the E. coli pyridoxine genes, but are found in the
      same archaebacteria, eubacteria, fungi, and plants that contain PDX1 homologues.
      PDX2 proteins are less well conserved than their PDX1 counterparts but contain
      several protein motifs that are conserved throughout all PDX2 proteins.

PMID- 11344147
TI  - Regulatory functions of serine-46-phosphorylated HPr in Lactococcus lactis.
AB  - In most low-G+C gram-positive bacteria, the phosphoryl carrier protein HPr of the
      phosphoenolpyruvate:sugar phosphotransferase system (PTS) becomes phosphorylated
      at Ser-46. This ATP-dependent reaction is catalyzed by the bifunctional HPr
      kinase/P-Ser-HPr phosphatase. We found that serine-phosphorylated HPr (P-Ser-HPr)
      of Lactococcus lactis participates not only in carbon catabolite repression of an
      operon encoding a beta-glucoside-specific EII and a 6-P-beta-glucosidase but also
      in inducer exclusion of the non-PTS carbohydrates maltose and ribose. In a wild
      type strain, transport of these non-PTS carbohydrates is strongly inhibited by
      the presence of glucose, whereas in a ptsH1 mutant, in which Ser-46 of HPr is
      replaced with an alanine, glucose had lost its inhibitory effect. In vitro
      experiments carried out with L. lactis vesicles had suggested that P-Ser-HPr is
      also implicated in inducer expulsion of nonmetabolizable homologues of PTS
      sugars, such as methyl beta-D-thiogalactoside (TMG) and 2-deoxy-D-glucose (2-DG).
      In vivo experiments with the ptsH1 mutant established that P-Ser-HPr is not
      necessary for inducer expulsion. Glucose-activated 2-DG expulsion occurred at
      similar rates in wild-type and ptsH1 mutant strains, whereas TMG expulsion was
      slowed in the ptsH1 mutant. It therefore seems that P-Ser-HPr is not essential
      for inducer expulsion but that in certain cases it can play an indirect role in
      this regulatory process.

PMID- 11344148
TI  - Identification and characterization of a second superoxide dismutase gene (sodM)
      from Staphylococcus aureus.
AB  - A gene encoding superoxide dismutase (SOD), sodM, from S. aureus was cloned and
      characterized. The deduced amino acid sequence specifies a 187-amino-acid protein
      with 75% identity to the S. aureus SodA protein. Amino acid sequence comparisons
      with known SODs and relative insensitivity to hydrogen peroxide and potassium
      cyanide indicate that SodM most likely uses manganese (Mn) as a cofactor. The
      sodM gene expressed from a plasmid rescued an Escherichia coli double mutant
      (sodA sodB) under conditions that are otherwise lethal. SOD activity gels of S.
      aureus RN6390 whole-cell lysates revealed three closely migrating bands of
      activity. The two upper bands were absent in a sodM mutant, while the two lower
      bands were absent in a sodA mutant. Thus, the middle band of activity most likely
      represents a SodM-SodA hybrid protein. All three bands of activity increased as
      highly aerated cultures entered the late exponential phase of growth, SodM more
      so than SodA. Viability of the sodA and sodM sodA mutants but not the sodM mutant
      was drastically reduced under oxidative stress conditions generated by methyl
      viologen (MV) added during the early exponential phase of growth. However, only
      the viability of the sodM sodA mutant was reduced when MV was added during the
      late exponential and stationary phases of growth. These data indicate that while
      SodA may be the major SOD activity in S. aureus throughout all stages of growth,
      SodM, under oxidative stress, becomes a major source of activity during the late
      exponential and stationary phases of growth such that viability and growth of an
      S. aureus sodA mutant are maintained.

PMID- 11344149
TI  - Rhizobial NodL O-acetyl transferase and NodS N-methyl transferase functionally
      interfere in production of modified Nod factors.
AB  - The products of the rhizobial nodulation genes are involved in the biosynthesis
      of lipochitin oligosaccharides (LCOs), which are host-specific signal molecules
      required for nodule formation. The presence of an O-acetyl group on C-6 of the
      nonreducing N-acetylglucosamine residue of LCOs is due to the enzymatic activity
      of NodL. Here we show that transfer of the nodL gene into four rhizobial species
      that all normally produce LCOs that are not modified on C-6 of the nonreducing
      terminal residue results in production of LCOs, the majority of which have an
      acetyl residue substituted on C-6. Surprisingly, in transconjugant strains of
      Mesorhizobium loti, Rhizobium etli, and Rhizobium tropici carrying nodL, such
      acetylation of LCOs prevents the endogenous nodS-dependent transfer of the N
      methyl group that is found as a substituent of the acylated nitrogen atom. To
      study this interference between nodL and nodS, we have cloned the nodS gene of M.
      loti and used its product in in vitro experiments in combination with purified
      NodL protein. It has previously been shown that a chitooligosaccharide N
      deacetylated on the nonreducing terminus (the so-called NodBC metabolite) is the
      preferred substrate for NodS as well as for NodL. Here we show that the NodBC
      metabolite, acetylated by NodL, is not used by the NodS protein as a substrate
      while the NodL protein can acetylate the NodBC metabolite that has been
      methylated by NodS.

PMID- 11344150
TI  - Identification and functional characterization of arylamine N-acetyltransferases
      in eubacteria: evidence for highly selective acetylation of 5-aminosalicylic
      acid.
AB  - Arylamine N-acetyltransferase activity has been described in various bacterial
      species. Bacterial N-acetyltransferases, including those from bacteria of the gut
      flora, may be involved in the metabolism of xenobiotics, thereby exerting
      physiopathological effects. We characterized these enzymes further by steady
      state kinetics, time-dependent inhibition, and DNA hybridization in 40 species,
      mostly from the human intestinal microflora. We report for the first time N
      acetyltransferase activity in 11 species of Proteobacteriaceae from seven genera:
      Citrobacter amalonaticus, Citrobacter farmeri, Citrobacter freundii, Klebsiella
      ozaenae, Klebsiella oxytoca, Klebsiella rhinoscleromatis, Morganella morganii,
      Serratia marcescens, Shigella flexneri, Plesiomonas shigelloides, and Vibrio
      cholerae. We estimated apparent kinetic parameters and found that 5
      aminosalicylic acid, a compound efficient in the treatment of inflammatory bowel
      diseases, was acetylated with a catalytic efficiency 27 to 645 times higher than
      that for its isomer, 4-aminosalicylic acid. In contrast, para-aminobenzoic acid,
      a folate precursor in bacteria, was poorly acetylated. Of the wild-type strains
      studied, Pseudomonas aeruginosa was the best acetylator in terms of both
      substrate spectrum and catalytic efficiency. DNA hybridization with a Salmonella
      enterica serovar Typhimurium-derived probe suggested the presence of this enzyme
      in eight proteobacterial and four gram-positive species. Molecular aspects
      together with the kinetic data suggest distinct functional features for this
      class of microbial enzymes.

PMID- 11344151
TI  - Novel type of glucose-6-phosphate isomerase in the hyperthermophilic archaeon
      Pyrococcus furiosus.
AB  - Glucose-6-phosphate isomerase (phosphoglucose isomerase [PGI]) (EC 5.3.1.9) from
      the hyperthermophilic archaeon Pyrococcus furiosus was purified 500-fold to
      homogeneity. The enzyme had an apparent molecular mass of 43 kDa and was composed
      of a single type of subunit of 23 kDa indicating a homodimeric (alpha(2))
      structure. Kinetic constants of the enzyme were determined at the optimal pH 7
      and at 80 degrees C. Rate dependence on both substrates followed Michaelis-Menten
      kinetics. The apparent K(m) values for glucose-6-phosphate and fructose-6
      phosphate were 8.7 and 1.0 mM, respectively, and the corresponding apparent
      V(max) values were 800 and 130 U/mg. The enzyme had a temperature optimum of 96
      degrees C and showed a significant thermostability up to 100 degrees C, which is
      in accordance with its physiological function under hyperthermophilic conditions.
      Based on the N-terminal amino acid sequence of the subunit, a single open reading
      frame (ORF; Pf_209264) was identified in the genome of P. furiosus. The ORF was
      characterized by functional overexpression in Escherichia coli as a gene, pgi,
      encoding glucose-6-phosphate isomerase. The recombinant PGI was purified and
      showed molecular and kinetic properties almost identical to those of the native
      PGI purified from P. furiosus. The deduced amino acid sequence of P. furiosus PGI
      did not reveal significant similarity to the conserved PGI superfamily of
      eubacteria and eucarya. This is the first description of an archaeal PGI, which
      represents a novel type of PGI.

PMID- 11344152
TI  - Regulation of expression of the vanD glycopeptide resistance gene cluster from
      Enterococcus faecium BM4339.
AB  - A new open reading frame, encoding a putative integrase-like protein, was
      detected downstream from the six genes of the vanD glycopeptide resistance
      cluster in Enterococcus faecium BM4339 (B. Casadewall and P. Courvalin, J.
      Bacteriol. 181:3644-3648, 1999). In this cluster, genes coding for the VanR(D)
      VanS(D) two-component regulatory system were cotranscribed from the P(R(D))
      promoter, whereas transcription of the vanY(D), vanH(D), vanD, vanX(D), and intD
      genes was initiated from the P(Y(D)) promoter located between vanS(D) and vanY(D)
      (the D subscript indicates that the gene is part of the vanD operon). The VanR(D)
      VanS(D) regulatory system is likely to activate transcription of the resistance
      genes from the promoter P(Y(D)). Glycopeptide-susceptible derivatives of BM4339
      were obtained by trans complementation of the frameshift mutation in the ddl
      gene, restoring functional D-alanine:D-alanine ligase activity in this strain.
      The glycopeptide-susceptible transformant BM4409, producing only D-alanyl-D
      alanine-terminating peptidoglycan precursors, did not express the resistance
      genes encoding the VanY(D) D,D-carboxypeptidase, the VanH(D) dehydrogenase, the
      VanD ligase, the VanX(D) D,D-dipeptidase, and also the IntD integrase, although
      the regulatory region of the vanD cluster was still transcribed. In BM4409, the
      absence of VanR(D)-VanS(D), apparently dependent, transcription from promoter
      P(Y(D)) correlated with the lack of D-alanyl-D-lactate-terminating precursors.
      The vanX(D) gene was transcribed in BM4339, but detectable amounts of VanX(D) D,D
      dipeptidase were not synthesized. However, the gene directed synthesis of an
      active enzyme when cloned on a multicopy plasmid in Escherichia coli, suggesting
      that the enzyme was unstable in BM4339 or that it had very low activity that was
      detectable only under conditions of high gene dosage. This activity is not
      required for glycopeptide resistance in BM4339, since this strain cannot
      synthesize D-alanyl-D-alanine.

PMID- 11344153
TI  - The CDC42 homolog of the dimorphic fungus Penicillium marneffei is required for
      correct cell polarization during growth but not development.
AB  - The opportunistic human pathogenic fungus Penicillium marneffei is dimorphic and
      is thereby capable of growth either as filamentous multinucleate hyphae or as
      uninucleate yeast cells which divide by fission. The dimorphic switch is
      temperature dependent and requires regulated changes in morphology and cell
      shape. Cdc42p is a Rho family GTPase which in Saccharomyces cerevisiae is
      required for changes in polarized growth during mating and pseudohyphal
      development. Cdc42p homologs in higher organisms are also associated with changes
      in cell shape and polarity. We have cloned a highly conserved CDC42 homolog from
      P. marneffei named cflA. By the generation of dominant-negative and dominant
      activated cflA transformants, we have shown that CflA initiates polarized growth
      and extension of the germ tube and subsequently maintains polarized growth in the
      vegetative mycelium. CflA is also required for polarization and determination of
      correct cell shape during yeast-like growth, and active CflA is required for the
      separation of yeast cells. However, correct cflA function is not required for
      dimorphic switching and does not appear to play a role during the generation of
      specialized structures during asexual development. In contrast, heterologous
      expression of cflA alleles in Aspergillus nidulans prevented conidiation.

PMID- 11344154
TI  - Twofold reduction of phosphofructokinase activity in Lactococcus lactis results
      in strong decreases in growth rate and in glycolytic flux.
AB  - Two mutant strains of Lactococcus lactis in which the promoter of the las operon,
      harboring pfk, pyk, and ldh, were replaced by synthetic promoters were
      constructed. These las mutants had an approximately twofold decrease in the
      activity of phosphofructokinase, whereas the activities of pyruvate kinase and
      lactate dehydrogenase remained closer to the wild-type level. In defined medium
      supplemented with glucose, the growth rate of the mutants was reduced to 57 to
      70% of wild-type levels and the glycolytic flux was reduced to 62 to 76% of wild
      type levels. In complex medium growth was even further reduced. Surprisingly, the
      mutants still showed homolactic fermentation, which indicated that the limitation
      was different from standard glucose-limited conditions. One explanation could be
      that the reduced activity of phosphofructokinase resulted in the accumulation of
      sugar-phosphates. Indeed, when one of the mutants was starved for glucose in
      glucose-limited chemostat, the growth rate could gradually be increased to 195%
      of the growth rate observed in glucose-saturated batch culture, suggesting that
      phosphofructokinase does affect the concentration of upstream metabolites. The
      pools of glucose-6-phosphate and fructose-6-phosphate were subsequently found to
      be increased two- to fourfold in the las mutants, which indicates that
      phosphofructokinase exerts strong control over the concentration of these
      metabolites.

PMID- 11344155
TI  - Characterization and analysis of the PikD regulatory factor in the pikromycin
      biosynthetic pathway of Streptomyces venezuelae.
AB  - The Streptomyces venezuelae pikD gene from the pikromycin biosynthetic cluster
      was analyzed, and its deduced product (PikD) was found to have amino acid
      sequence homology with a small family of bacterial regulatory proteins. Database
      comparisons revealed two hypothetical domains, including an N-terminal
      triphosphate-binding domain and a C-terminal helix-turn-helix DNA-binding motif.
      Analysis of PikD was initiated by deletion of the corresponding gene (pikD) from
      the chromosome of S. venezuelae, resulting in complete loss of antibiotic
      production. Complementation by a plasmid carrying pikD restored macrolide
      biosynthesis, demonstrating that PikD is a positive regulator. Mutations were
      made in the predicted nucleotide triphosphate-binding domain, confirming the
      active-site amino acid residues of the Walker A and B motifs. Feeding of
      macrolide intermediates was carried out to gauge the points of operon control by
      PikD. Although the pikD mutant strain was unable to convert macrolactones (10
      deoxymethynolide and narbonolide) to glycosylated products, macrolide
      intermediates (YC-17 and narbomycin) were hydroxylated with high efficiency. To
      study further the control of biosynthesis, presumed promoter regions from pik
      cluster loci were linked to the xylE reporter and placed in S. venezuelae wild
      type and pikD mutant strains. This analysis demonstrated that PikD-mediated
      transcriptional regulation occurs at promoters controlling expression of pikRII,
      pikAI, and desI but not those controlling pikRI or pikC.

PMID- 11344156
TI  - FhuA barrel-cork hybrids are active transporters and receptors.
AB  - The crystal structure of Escherichia coli FhuA reveals a beta-barrel domain that
      is closed by a globular cork domain. It has been assumed that the proton motive
      force of the cytoplasmic membrane through the interaction of the TonB protein
      with the TonB box of the cork opens the FhuA channel. Yet, deletion of the cork
      results in an FhuA derivative, FhuADelta5-160, that still displays TonB-dependent
      substrate transport and phage receptor activity. To investigate this unexpected
      finding further, we constructed FhuADelta5-160 derivatives of FhuA proteins from
      Salmonella paratyphi B, Salmonella enterica serovar Typhimurium, and Pantoea
      agglomerans. The FhuADelta5-160 proteins inserted correctly into the outer
      membrane, and with the exception of the P. agglomerans protein, transported
      ferrichrome and albomycin. FhuA hybrids consisting of the beta-barrel of one
      strain and the cork of another strain were active and showed higher TonB
      dependent ferrichrome transport rates than the corkless derivatives. Exceptions
      were the E. coli beta-barrel/Salmonella serovar Typhimurium cork hybrid protein
      and the Salmonella serovar Typhimurium beta-barrel/P. agglomerans cork hybrid
      protein, both of which were less active than the beta-barrels alone. Each of the
      FhuA mutant proteins displayed activity for each of their ligands, except for
      phage T5, only when coupled to TonB. The hybrid FhuA proteins displayed a similar
      activity with the E. coli TonB protein as with their cognate TonB proteins.
      Sensitivity to phages T1, T5, and phi80, rifamycin CGP 4832, and colicin M was
      determined by the beta-barrel, whereas sensitivity to phage ES18 and microcin J25
      required both the beta-barrel and cork domains. These results demonstrate that
      the beta-barrel domain of FhuA confers activity and specificity and responds to
      TonB and that the cork domains of various FhuA proteins can be interchanged and
      contribute to the activities of the FhuA hybrids.

PMID- 11344157
TI  - Functional analysis of relA and rshA, two relA/spoT homologues of Streptomyces
      coelicolor A3(2).
AB  - Deletion of the (p)ppGpp synthetase gene, relA, of Streptomyces coelicolor A3(2)
      results in loss of production of the antibiotics actinorhodin (Act) and
      undecylprodigiosin (Red) and delayed morphological differentiation when the
      mutant is grown under conditions of nitrogen limitation. To analyze the role of
      (p)ppGpp as an intracellular signaling molecule for the initiation of antibiotic
      production, several C-terminally deleted derivatives of S. coelicolor relA that
      could potentially function in the absence of ribosome activation were placed
      under the control of the thiostrepton-inducible tipA promoter. While 0.82- and
      1.28-kb N-terminal segments failed to restore (p)ppGpp and antibiotic production
      upon induction in a relA null mutant, 1.46- and 2.07-kb segments did. Under
      conditions of phosphate limitation, deletion of relA had little or no effect on
      Act or Red synthesis, potentially reflecting an alternative mechanism for ppGpp
      synthesis. A second S. coelicolor RelA homologue (RshA, with 42% identity to S.
      coelicolor RelA) was identified in the genome sequence. However, deletion of rshA
      had no effect on the ability of the relA mutant to make Act and Red when grown
      under conditions of phosphate limitation. While high-level induction of
      tipAp::rshA in the relA mutant resulted in growth inhibition, low-level induction
      restored antibiotic production and sporulation. In neither case, nor in the relA
      mutant that was grown under phosphate limitation and producing Act and Red, could
      (p)ppGpp synthesis be detected. Thus, a ppGpp-independent mechanism exists to
      activate antibiotic production under conditions of phosphate limitation that can
      be mimicked by overexpression of rshA.

PMID- 11344158
TI  - Evidence against an Interaction between the mRNA downstream box and 16S rRNA in
      translation initiation.
AB  - Based on the complementarity of the initial coding region (downstream box [db])
      of several bacterial and phage mRNAs to bases 1469 to 1483 in helix 44 of 16S
      rRNA (anti-downstream box [adb]), it has been proposed that db-adb base pairing
      enhances translation in a way that is similar to that of the Shine-Dalgarno
      (SD)/anti-Shine-Dalgarno (aSD) interaction. Computer modeling of helix 44 on the
      30S subunit shows that the topography of the 30S ribosome does not allow a
      simultaneous db-adb interaction and placement of the initiation codon in the
      ribosomal P site. Thus, the db-adb interaction cannot substitute for the SD-aSD
      interaction in translation initiation. We have always argued that any
      contribution of the db-adb interaction should be most apparent on mRNAs devoid of
      an SD sequence. Here, we show that 30S ribosomes do not bind to leaderless mRNA
      in the absence of initiator tRNA, even when the initial coding region shows a 15
      nucleotide complementarity (optimal fit) with the putative adb. In addition, an
      optimized db did not affect the translational efficiency of a leaderless lambda
      cI-lacZ reporter construct. Thus, the db-adb interaction can hardly serve as an
      initial recruitment signal for ribosomes. Moreover, we show that different
      leaderless mRNAs are translated in heterologous systems although the sequence of
      the putative adb's within helix 44 of the 30S subunits of the corresponding
      bacteria differ largely. Taken our data together with those of others (M.
      O'Connor, T. Asai, C. L. Squires, and A. E. Dahlberg, Proc. Natl. Acad. Sci. USA
      96:8973-8978, 1999; A. La Teana, A. Brandi, M. O'Connor, S. Freddi, and C. L.
      Pon, RNA 6:1393-1402, 2000), we conclude that the db does not base pair with the
      adb.

PMID- 11344160
TI  - Improvement in K+-limited growth rate associated with expression of the N
      terminal fragment of one subunit (KdpA) of the multisubunit Kdp transporter in
      Escherichia coli.
AB  - Mutations in any one of three genes, kdpA, -B, or -C, in Escherichia coli abolish
      the activity of Kdp, a multisubunit K+-ATPase that belongs to the P-type ATPase
      family of cation transporters. We found in this study that expression in vivo of
      a 135-amino-acid-long N-terminal fragment (KdpA'), less than one-quarter the
      length of native KdpA, was able to mediate an improvement in K+-limited growth
      rates in two different contexts, even in the absence of both KdpC and the ATPase
      subunit KdpB. The first context was when KdpA' was overexpressed in cells from a
      heterologous inducible promoter, and the second was when KdpA' was provided with
      a C-terminally altered extension (following a spontaneous genetic rearrangement).
      Our results suggest that KdpA' provides an incipient pathway for K+ translocation
      which can serve to transport K+ into the cells in response to the cytoplasmic
      membrane potential.

PMID- 11344159
TI  - Biosynthesis of the glycolipid anchor in lipoteichoic acid of Staphylococcus
      aureus RN4220: role of YpfP, the diglucosyldiacylglycerol synthase.
AB  - In Staphylococcus aureus RN4220, lipoteichoic acid (LTA) is anchored in the
      membrane by a diglucosyldiacylglycerol moiety. The gene (ypfP) which encodes
      diglucosyldiacylglycerol synthase was recently cloned from Bacillus subtilis and
      expressed in Escherichia coli (P. Jorasch, F. P. Wolter, U. Zahringer, and E.
      Heinz, Mol. Microbiol. 29:419-430, 1998). To define the role of ypfP in this
      strain of S. aureus, a fragment of ypfP truncated from both ends was cloned into
      the thermosensitive replicon pVE6007 and used to inactivate ypfP. Chloramphenicol
      resistant (ypfP::cat) clones did not synthesize the glycolipids
      monoglucosyldiacylglycerol and diglucosyldiacylglycerol. Thus, YpfP would appear
      to be the only diglucosyldiacylglycerol synthase in S. aureus providing
      glycolipid for LTA assembly. In LTA from the mutant, the glycolipid anchor is
      replaced by diacylglycerol. Although the doubling time of the mutant was
      identical to that of the wild type in Luria-Bertani (LB) medium, growth of the
      mutant in LB medium containing 1% glycine was not observed. This inhibition was
      antagonized by either L- or D-alanine. Moreover, viability of the mutant at 37
      degrees C in 0.05 M phosphate (pH 7.2)-saline for 12 h was reduced to <0.1%.
      Addition of 0.1% D-glucose to the phosphate-saline ensured viability under these
      conditions. The autolysis of the ypfP::cat mutant in the presence of 0.05% Triton
      X-100 was 1.8-fold faster than that of the parental strain. Electron microscopy
      of the mutant revealed not only a small increase in cell size but also the
      presence of pleomorphic cells. Each of these phenotypes may be correlated with
      either (or both) a deficiency of free glycolipid in the membrane or the
      replacement of the usual glycolipid anchor of LTA with diacylglycerol.

PMID- 11344162
TI  - Beta-ketoacyl acyl carrier protein synthase III (FabH) is essential for fatty
      acid biosynthesis in Streptomyces coelicolor A3(2).
AB  - The Streptomyces coelicolor fab (fatty acid biosynthesis) gene cluster (fabD-fabH
      acpP-fabF) is cotranscribed to produce a leaderless mRNA transcript. One of these
      genes, fabH, encodes a ketoacyl synthase III that is essential to and is proposed
      to be responsible for initiation of fatty acid biosynthesis in S. coelicolor.

PMID- 11344161
TI  - RegG, a CcpA homolog, participates in regulation of amylase-binding protein A
      gene (abpA) expression in Streptococcus gordonii.
AB  - The amylase-binding protein A (AbpA) of Streptococcus gordonii was found to be
      undetectable in supernatants of mid-log-phase cultures containing >1% glucose but
      abundant in supernatants of cultures made with brain heart infusion (BHI), which
      contains 0.2% glucose. A 10-fold decrease in the level of abpA mRNA in S.
      gordonii cells cultured in BHI was noted after the addition of glucose to 1%.
      Analysis of the abpA sequence revealed a potential catabolite responsive element
      CRE 153 bp downstream of the putative translational start site. A catabolite
      control protein A gene (ccpA) homolog from S. gordonii, designated regG, was
      cloned. A regG mutant strain demonstrated moderately less repression of abpA
      transcription in the presence of 1% glucose. Diauxic growth with glucose and
      lactose was not affected in the RegG mutant compared to the wild-type parental
      strain. These results suggest that while RegG plays a role in abpA expression,
      other mechanisms of catabolite repression are present.

PMID- 11344163
TI  - Multiple mobile promoter regions for the rare carbapenem resistance gene of
      Bacteroides fragilis.
AB  - Two novel insertion sequences (IS), IS1187 and IS1188, are described upstream
      from the carbapenem resistance gene cfiA in strains of Bacteroides fragilis.
      Mapping, with the RACE procedure, of transcription start sites of cfiA in these
      and two other previously reported IS showed that transcription of this rarely
      encountered gene is initiated close to a variety of B. fragilis consensus
      promoter sequences, as recently defined (D. P. Bayley, E. R. Rocha, and C. J.
      Smith, FEMS Microbiol. Lett. 193:149-154, 2000). In the cases of IS1186 and
      IS1188, these sequences overlap with putative Esigma(70) promoter sequences,
      while in IS942 and IS1187 such sequences can be observed either upstream or
      downstream of the B. fragilis promoters.

PMID- 11344164
TI  - Combined antisense and pharmacological approaches implicate hTASK as an airway
      O(2) sensing K(+) channel.
AB  - Neuroepithelial bodies act as airway oxygen sensors. The lung carcinoma line H146
      is an established model for neuroepithelial body cells. Although O(2) sensing in
      both cells is via NADPH oxidase H(2)O(2)/free radical production and acute
      hypoxia promotes K(+) channel closure and cell depolarization, the identity of
      the K(+) channel is still controversial. However, recent data point toward the
      involvement of a member of the tandem P domain family of K(+) channels. Reverse
      transcription-polymerase chain reaction screening indicates that all known
      channels other than hTWIK1 and hTRAAK are expressed in H146 cells. Our detailed
      pharmacological characterization of the O(2)-sensitive K(+) current described
      herein is compatible with the involvement of hTASK1 or hTASK3 (pH dependence,
      tetraethylammonium and dithiothreitol insensitivity, blockade by arachidonic
      acid, and halothane activation). Furthermore, we have used antisense
      oligodeoxynucleotides directed against hTASK1 and hTASK3 to suppress almost
      completely the hTASK1 protein and show that these cells no longer respond to
      acute hypoxia; this behavior was not mirrored in liposome-only or missense
      treated cells. Finally, we have used Zn(2+) treatment as a maneuver able to
      discriminate between these two homologues of hTASK and show that the most likely
      candidate channel for O(2) sensing in these cells is hTASK3.

PMID- 11344165
TI  - A novel viper venom metalloproteinase, alborhagin, is an agonist at the platelet
      collagen receptor GPVI.
AB  - The interaction of platelet membrane glycoprotein VI (GPVI) with collagen can
      initiate (patho)physiological thrombus formation. The viper venom C-type lectin
      family proteins convulxin and alboaggregin-A activate platelets by interacting
      with GPVI. In this study, we isolated from white-lipped tree viper (Trimeresurus
      albolabris) venom, alborhagin, which is functionally related to convulxin because
      it activates platelets but is structurally different and related to venom
      metalloproteinases. Alborhagin-induced platelet aggregation (EC50, <7.5
      microg/ml) was inhibitable by an anti-alphaIIbbeta3 antibody, CRC64, and the Src
      family kinase inhibitor PP1, suggesting that alborhagin activates platelets,
      leading to alphaIIbbeta3-dependent aggregation. Additional evidence suggested
      that, like convulxin, alborhagin activated platelets by a mechanism involving
      GPVI. First, alborhagin- and convulxin-treated platelets showed a similar
      tyrosine phosphorylation pattern, including a similar level of phospholipase
      Cgamma2 phosphorylation. Second, alborhagin induced GPVI-dependent responses in
      GPVI-transfected K562 and Jurkat cells. Third, alborhagin-dependent aggregation
      of mouse platelets was inhibited by the anti-GPVI monoclonal antibody JAQ1.
      Alborhagin had minimal effect on convulxin binding to GPVI-expressing cells,
      indicating that these venom proteins may recognize distinct binding sites.
      Characterization of alborhagin as a GPVI agonist that is structurally distinct
      from convulxin demonstrates the versatility of snake venom toxins and provides a
      novel probe for GPVI-dependent platelet activation.

PMID- 11344167
TI  - Interaction of FACT, SSRP1, and the high mobility group (HMG) domain of SSRP1
      with DNA damaged by the anticancer drug cisplatin.
AB  - The structure-specific recognition protein SSRP1, initially isolated from
      expression screening of a human B-cell cDNA library for proteins that bind to
      cisplatin (cis-diamminedichloroplatinum(II))-modified DNA, contains a single DNA
      binding high mobility group (HMG) domain. Human SSRP1 purifies as a heterodimer
      of SSRP1 and Spt16 (FACT) that alleviates the nucleosomal block to transcription
      elongation by RNAPII in vitro. The affinity and specificity of FACT, SSRP1, and
      the isolated HMG domain of SSRP1 for cisplatin-damaged DNA were investigated by
      gel mobility shift assays. FACT exhibits both affinity and specificity for DNA
      damaged globally with cisplatin compared with unmodified DNA or DNA damaged
      globally with the clinically ineffective trans-DDP isomer. FACT binds the major
      1,2-d(GpG) intrastrand cisplatin adduct, but its isolated SSRP1 subunit fails to
      form discrete, high affinity complexes with cisplatin-modified DNA under similar
      conditions. These results suggest that Spt16 primes SSRP1 for cisplatin-damaged
      DNA recognition by unveiling its HMG domain. As expected, the isolated HMG domain
      of SSRP1 is sufficient for specific binding to cisplatin-damaged DNA and binds
      the major cisplatin 1,2-d(GpG) intrastrand cross-link. The affinity and
      specificity of FACT for cisplatin-modified DNA, as well as its importance for
      transcription of chromatin, suggests that the interaction of FACT and cisplatin
      damaged DNA may be crucial to the anticancer mechanism of cisplatin.

PMID- 11344166
TI  - Essential role of Sna41/Cdc45 in loading of DNA polymerase alpha onto
      minichromosome maintenance proteins in fission yeast.
AB  - Assembly of replication complexes at the replication origins is strictly
      regulated. Cdc45p is known to be a part of the active replication complexes. In
      Xenopus egg extracts, Cdc45p was shown to be required for loading of DNA
      polymerase alpha onto chromatin. The fission yeast cdc45 homologue was identified
      as a suppressor for nda4 and named sna41. Nevertheless, it is not known how
      Cdc45p facilitates loading of DNA polymerase alpha onto chromatin, particularly
      to prereplicative complexes. To gain novel insight into the function of this
      protein in fission yeast, we characterized the fission yeast Cdc45 homologue,
      Sna41p. We have constructed C-terminally epitope-tagged Sna41p and Pol alpha p
      and replaced the endogenous genes with the corresponding tagged genes. Analyses
      of protein-protein interactions in vivo by the use of these tagged strains
      revealed the following: Sna41p interacts with Pol alpha p throughout the cell
      cycle, whereas it interacts with Mis5p/Mcm6p in the chromatin fractions at the
      G(1)-S boundary through S phase. In an initiation-defective sna41 mutant,
      sna41(goa1), interaction of Pol alpha p with Mis5p is not observed, although Pol
      alpha p loading onto the chromatin that occurs before G(1) START is not affected.
      These results show that fission yeast Sna41p facilitates the loading of Pol alpha
      p onto minichromosome maintenance proteins. Our results are consistent with a
      model in which loading of Pol alpha p onto replication origins occurs through two
      steps, namely, loading onto chromatin at preSTART and association with
      prereplicative complexes at G(1)-S through Sna41p, which interacts with
      minichromosome maintenance proteins in a cell cycle-dependent manner.

PMID- 11344168
TI  - Modular structure of the TIM23 preprotein translocase of mitochondria.
AB  - The TIM23 complex mediates import into mitochondria of nuclear encoded
      preproteins with a matrix-targeting signal. It is composed of the integral
      membrane proteins Tim17 and Tim23 and the peripheral membrane protein Tim44,
      which recruits mitochondrial Hsp70 to the sites of protein import. We have
      analyzed the functions of these constituents using a combined genetic and
      biochemical approach. Depletion of either Tim17 or Tim23 led to loss of import
      competence of mitochondria and to a reduction in the number of preprotein
      conducting channels. Upon depletion of Tim44, mitochondria also lost their
      ability to import proteins but maintained normal numbers of import channels. In
      the absence of Tim44 precursor protein was specifically recognized. The
      presequence was translocated in a Delta psi-dependent manner across the inner
      membrane and cleaved by matrix-processing peptidase. However, the preprotein did
      not move further into the matrix but rather underwent retrograde sliding out of
      the TIM23 complex. Thus, the TIM23 complex is composed of functionally
      independent modules. Tim17 and Tim23 are necessary for initiating translocation,
      whereas Tim44 and mitochondrial Hsp70 are indispensable for complete transport of
      preproteins and for unfolding of folded domains of preproteins.

PMID- 11344169
TI  - Platelet activation by von Willebrand factor requires coordinated signaling
      through thromboxane A2 and Fc gamma IIA receptor.
AB  - Interaction of von Willebrand Factor with glycoprotein Ib-IX-V induces platelet
      activation through a still poorly defined mechanism. Previous studies have
      suggested a possible role for the low affinity receptor for immunoglobulin, Fc
      gamma RIIA, in GPIb-IX-V signaling. Here we show that binding of vWF to platelets
      induces the tyrosine phosphorylation of Fc gamma RIIA by a Src kinase. Treatment
      of platelets with the anti-Fc gamma RIIA monoclonal antibody IV.3 specifically
      inhibits vWF-induced but not thrombin-induced pleckstrin phosphorylation and
      serotonin secretion. Moreover, vWF fails to induce pleckstrin phosphorylation in
      mouse platelets, lacking Fc gamma RIIA, and serotonin secretion is impaired.
      Pleckstrin phosphorylation and serotonin secretion in human platelets stimulated
      with vWF are blocked by the cyclooxygenase inhibitor acetylsalicylic acid.
      However, release of arachidonic acid and synthesis of TxA(2) induced by vWF are
      not affected by the anti-Fc gamma RIIA monoclonal antibody IV.3. Similarly, vWF
      induced tyrosine phosphorylation of Fc gamma RIIA, as well as of Syk and PLC
      gamma 2, occurs normally in aspirinized platelets. Inhibition of the tyrosine
      kinase Syk by piceatannol does not affect vWF-induced tyrosine phosphorylation of
      Fc gamma RIIA but prevents phosphorylation of PLC gamma 2. Pleckstrin
      phosphorylation and platelet secretion induced by vWF, but not by thrombin, are
      also inhibited by piceatannol. Pleckstrin phosphorylation is also sensitive to
      the phosphatidylinositol 3-kinase inhibitor wortmannin. These results indicate
      that PLC gamma 2 plays a central role in platelet activation by vWF and that the
      stimulation of this enzyme requires coordinated signals through endogenous TxA(2)
      and Fc gamma RIIA.

PMID- 11344170
TI  - Clinical review 129: Oral cholecystographic agents and the thyroid.
AB  - Oral cholecystographic agents (OCAs) are known to affect thyroid hormone
      metabolism by acting as potent inhibitors of type I and type II deiodinases,
      blocking the conversion of T(4) to T(3) and rT(3) to T(2). In addition, iodine
      released from the drug blocks thyroid gland secretion of thyroid hormone. These
      properties make OCAs a potentially useful drug therapy in patients with
      hyperthyroidism and other thyrotoxic disorders. Short-term treatment with OCAs
      rapidly reduces serum T(3) levels, with a lesser effect on T(4) levels. OCAs are
      not useful for long-term treatment, which is usually followed by exacerbation of
      hyperthyroidism with continued use. The lack of significant side effects makes
      these drugs an excellent short-term option in situations where a rapid clinical
      improvement is critical.

PMID- 11344171
TI  - Distinct radiological and clinical appearance of lymphocytic hypophysitis.

PMID- 11344172
TI  - Thyroid storm in a child following radioactive iodine (RAI) therapy: a
      consequence of RAI versus withdrawal of antithyroid medication.
AB  - A 7.5-yr-old boy with Graves' disease, difficult to control with antithyroid
      medication and radioactive iodine (RAI) therapy, developed thyroid storm
      encephalopathy on day 13 after withdrawal of methimazole therapy, 4 days after
      iodine-131 treatment. We attributed his thyroid storm to withdrawal of
      antithyroid medication as opposed to RAI therapy. We interpret this case as
      indicating that there may be a need to reevaluate the duration of antithyroid
      medication withdrawal before RAI therapy for hyperthyroid children at increased
      risk for thyroid storm.

PMID- 11344173
TI  - Critical evaluation of the safety of recombinant human growth hormone
      administration: statement from the Growth Hormone Research Society.

PMID- 11344174
TI  - Growth hormone and cardiovascular disease: an area in rapid growth.

PMID- 11344175
TI  - Improved cardiovascular risk factors and cardiac performance after 12 months of
      growth hormone (GH) replacement in young adult patients with GH deficiency.
AB  - Adult GH deficiency (GHD) is associated with increased cardiovascular morbidity
      and mortality due to unfavorable lipid profile, hyperfibrinogenemia, and
      impairment of cardiac performance. This prospective controlled cohort study
      evaluated the effects of 12-month GH replacement on lipid profile, fibrinogen
      levels, cardiac mass by echocardiography, and performance by equilibrium
      radionuclide angiography. To this end we studied 20 patients (11 men and 9 women,
      aged 19-40 yr), 10 with childhood-onset (co-) and 10 with adult-onset (ao-)
      disease, and 20 sex- and age-matched healthy subjects. At study entry, insulin
      like growth factor I (IGF-I; P < 0.0001) and high density lipoprotein (HDL)
      cholesterol (P < 0.0001) levels, left ventricular mass index (LVMi; P < 0.0001),
      ejection fraction (LVEF) at rest (P = 0.001) and at peak exercise (P < 0.0001),
      peak ejection rate (P = 0.005), and exercise duration (P < 0.0001) and capacity
      (P = 0.002) were lower, whereas total cholesterol (P = 0.02), triglycerides (P =
      0.003), and fibrinogen (P = 0.005) levels were higher in patients than in
      controls. After 12 months, increases in IGF-I (P < 0.0001) and HDL cholesterol
      levels (P = 0.04), LVMi (P < 0.0001), LVEF at peak exercise (P < 0.0001), and
      exercise duration (P = 0.009) and capacity (P = 0.003) and decreases in total
      cholesterol (P < 0.0001), low density lipoprotein cholesterol (P < 0.0001),
      triglycerides (P < 0.0001), and fibrinogen (P = 0.01) levels were found in all
      patients, without any difference between co- and ao-GHD. At the end of treatment,
      however, total cholesterol, triglycerides, and fibrinogen levels were still
      higher, and HDL cholesterol levels, IGF-I levels, and LVEF at rest and at peak
      exercise were lower in patients than in controls. In conclusion, GH replacement
      for 12 months significantly improved lipid profile, decreased fibrinogen levels,
      and increased LVMi and LVEF in young adults with co- or ao-GHD. However, lipid
      profile, fibrinogen levels, and systolic function remained abnormal compared with
      those in age- and sex-matched controls, suggesting that a longer period of GH
      replacement is necessary to normalize cardiovascular parameters and reverse the
      cardiovascular risk of these patients.

PMID- 11344176
TI  - The not-so-odd couple--the clinician and the experimentalist.

PMID- 11344177
TI  - Serum leptin levels are associated with bone mass in nonobese women.
AB  - Both serum leptin and bone mineral density are positively correlated with body
      fat, generating the hypothesis that leptin may be a systemic and/or local
      regulator of bone mass. We investigated 214 healthy, nonobese Australian women
      aged 20-91 yr. Bone mineral content, projected bone area, and body fat mass were
      measured by dual energy x-ray absorptiometry and fasting serum leptin levels by
      RIA. Associations between bone mineral content (adjusted for age, body weight,
      body fat mass, and bone area) and the natural logarithm of serum leptin
      concentrations were analyzed by multiple regression techniques. There was a
      significant positive association at the lateral spine, two proximal femur sites
      (Ward's triangle and trochanter), and whole body (partial r(2) = 0.019 to 0.036;
      all P < 0.05). Similar trends were observed at the femoral neck and posterior
      anterior-spine. With bone mineral density the dependent variable (adjusted for
      age, body weight, and body fat mass), the association with the natural logarithm
      of leptin remained significant at the lateral spine (partial r(2) = 0.030; P =
      0.011), was of borderline significance at the proximal femur sites (partial r(2)
      = 0.012 to 0.017; P = 0.058 to 0.120), and was not significant at the other
      sites. Our results demonstrate an association between serum leptin levels and
      bone mass consistent with the hypothesis that circulating leptin may play a role
      in regulating bone mass.

PMID- 11344178
TI  - The role of combination treatment for osteoporosis.

PMID- 11344179
TI  - Effect of combined risedronate and hormone replacement therapies on bone mineral
      density in postmenopausal women.
AB  - Both hormone replacement therapy (HRT) and bisphosphonates are efficacious in the
      prevention and treatment of postmenopausal osteoporosis. Combined therapy with
      bisphosphonate and HRT is likely to be used in clinical practice, and limited
      data are available regarding its efficacy and safety. This was a 1-yr, double
      blind, placebo-controlled study in which 524 postmenopausal women received daily
      treatment with conjugated equine estrogens (0.625 mg) alone or in combination
      with risedronate (5 mg). Women who had not undergone hysterectomy received
      medroxyprogesterone acetate (up to 5 mg, daily or cyclically) at the discretion
      of the investigator. The primary efficacy end point was the percent change from
      baseline in mean lumbar spine bone mineral density (BMD) at 1 yr. Changes in BMD
      at the proximal femur and forearm, bone turnover markers, and histology and
      histomorphometry were also assessed. At 12 months, significant (P < 0.05)
      increases from baseline in lumbar spine BMD were observed in both treatment
      groups (HRT-only, 4.6%; combined risedronate-HRT, 5.2%); the difference between
      the two groups was not statistically significant. Both therapies led to
      significant increases in BMD at 12 months at the femoral neck (1.8% and 2.7%,
      respectively), femoral trochanter (3.2% and 3.7%), distal radius (1.7% and 1.6%),
      and midshaft radius (0.4% and 0.7%). The differences between groups were
      statistically significant (P < 0.05) at the femoral neck and midshaft radius.
      Both combined risedronate-HRT and HRT-only produced significant decreases in the
      biochemical markers of bone turnover, with somewhat greater decreases in the
      combined treatment group. Bone biopsy data showed normal bone structure and
      normal mineralization with either treatment. Expected decreases in bone turnover
      were observed and were greater in the combined treatment group (68-79% reduction
      relative to baseline values, P < 0.005). Overall, combined treatment had a safety
      profile similar to that of HRT-only, including bone and gastrointestinal safety
      profiles. In conclusion, the combined treatment with risedronate and HRT had a
      favorable effect on BMD similar to that of HRT alone at the lumbar spine and
      slightly, but significantly, greater than that of HRT alone at the femoral neck
      and midshaft radius. The combined treatment was well tolerated, and there were no
      adverse effects on the skeleton.

PMID- 11344180
TI  - La plus ca change, la plus c'est la meme chose--will bioassays make a comeback?

PMID- 11344181
TI  - The effect of administering gonadotropin-releasing hormone agonist with
      recombinant-human growth hormone (GH) on the final height of girls with isolated
      GH deficiency: results from a controlled study.
AB  - To assess whether delaying puberty may improve final height in GH-deficient
      children with a poor height prediction at early puberty, we studied 24 girls with
      isolated GH deficiency until they reached their final height, in a controlled
      trial. Patients were taking recombinant human GH (r-hGH) substitutive therapy
      from 2.1 +/- 0.5 yr (0.1 IU/kg.day sc) before entering the study, without showing
      any improvement in height prediction (149.6 +/- 2.9 vs.150.3 +/- 2.2 cm) on
      entering puberty. Fourteen girls agreed to add a GnRH agonist (GnRHa) to r-hGH,
      whereas the remaining 10 decided against it and served as controls. At the start
      of the study, girls treated with or without GnRHa had similar auxological
      characteristics (bone age, 10.9 +/- 0.6 vs. 10.7 +/- 1.3 yr; height SD score for
      chronological age, -1.87 +/- 0.3 vs. -1.82 +/- 0.2), including pubertal
      development. The GnRHa (long-acting D-Trp-6-GnRH) was given at 60 microg/kg im
      every 28 days for 1.9 +/- 0.9 yr, then patients continued the r-hGH at the same
      dosage (3.1 +/- 0.7 yr). At the end of the study, bone age was 16.2 +/- 0.3 yr in
      GnRHa-treated girls and 16.6 +/- 0.9 yr in controls. Bone maturation was
      significantly slower during GnRHa (1.4 +/- 0.2 yr), and height SD score for bone
      age improved (-0.31 +/- 0.3) in comparison with controls (2.6 +/- 0.4 yr and 
      1.35 +/- 0.3 SD score; P < 0.001 and P < 0.0001, respectively). As a result,
      girls given the combined therapy reached a final height higher than that of
      controls (height SD score, -0.39 +/- 0.5 vs. -1.45 +/- 0.2; P < 0.0001) and also
      higher than their midparental height (-1.1 +/- 0.5; P < 0.0005). Controls reached
      their midparental height. In conclusion, our results demonstrate that slowing
      pubertal development with the administration of GnRHa for a limited time may
      improve final height in GH-deficient girls selected because of a poor height
      prediction at early puberty.

PMID- 11344182
TI  - The "quality of life-assessment of growth hormone deficiency in adults"
      questionnaire: can it be used to assess quality of life in hypopituitarism?
AB  - Patients with hypopituitarism often have a multitude of physical and
      psychological complaints, collectively referred to as low quality of life (QoL).
      It has been asserted that GH deficiency (GHD) is the causative factor, and
      improved QoL scores have been reported during GH replacement. Qol-assessment of
      GHD (QoL-AGHDA) is the newest psychometric instrument with the purportedly high
      specificity for the issues encountered by patients with GHD. QoL-AGHDA was
      administered to 30 normal control subjects, 20 patients with severe GHD, and 22
      patients with active acromegaly. QoL-AGHDA scores in controls (3.3 +/- 0.7) were
      significantly (P < 0.001) different from those in patients with hypopituitarism
      with unsubstituted GHD (10.6 +/- 1.5) and active acromegaly (11.6 +/- 1.6).
      However, QoL-AGHDA was unable to discriminate between the latter two groups, one
      with GHD and the other with GH excess. We conclude that as QoL-AGHDA cannot
      distinguish between the extremes of GH output, its ability to detect an
      improvement in QoL during GH replacement has to be viewed with skepticism. This
      can be dispelled only by double blind, placebo-controlled studies.

PMID- 11344183
TI  - The role of the vitamin D receptor in regulating vitamin D metabolism: a study of
      vitamin D-dependent rickets, type II.
AB  - In vitro studies and animal experiments suggest that the production of 1,25
      dihydroxyvitamin D [1,25-(OH)(2)D] and 24,25-(OH)(2)D is reciprocally controlled
      by 1,25-(OH)(2)D. To investigate the role of the vitamin D receptor (VDR) in
      controlling vitamin D metabolism in humans, we studied 10 patients with vitamin D
      dependent rickets type II due to a defective VDR. After a period of high dose
      calcium therapy, 7 of the patients had normal serum calcium, phosphorus, alkaline
      phosphatase, and plasma PTH levels (PTH-N), and 3 showed increased serum alkaline
      phosphatase and plasma PTH (PTH-H). Serum calcium, phosphorus, alkaline
      phosphatase, PTH, vitamin D metabolites, urinary calcium/creatinine, and renal
      phosphate threshold concentration were compared with unaffected family members
      that comprised the control group. Vitamin D metabolites were measured before and
      after an oral load of 50,000 U/m(2) cholecalciferol. Compared with the control
      group, 1,25-(OH)(2)D levels were significantly higher and 24,25-(OH)(2)D levels
      were lower in the PTH-N group and even more so in the PTH-H group. 1alpha
      Hydroxylase (1-OHase) and 24-OHase activities were estimated by the
      product/substrate ratio. In the PTH-N group, 1-OHase activity was higher and 24
      OHase activity was lower than in controls. In the PTH-H group, 1-OHase activity
      was even higher, probably due to an additive effect of PTH. Thus, 1,25-(OH)(2)D
      liganded VDR is a major control mechanism for vitamin D metabolism, and PTH
      exerts an additive effect. Assessment of the influence of 1,25-(OH)(2)D shows
      reciprocal control of enzyme activity in man, suppressing 1-OHase and stimulating
      24-OHase activity.

PMID- 11344184
TI  - A randomized controlled trial of low-dose recombinant human growth hormone in the
      treatment of malnourished elderly medical patients.
AB  - High-dose recombinant human GH (rhGH) has been shown to improve the nutritional
      status of malnourished older adults. It is uncertain whether low-dose rhGH is
      effective and whether its effect on nutritional status will lead to any
      improvement in physical function. There is also no data on the outcome after a
      short course of rhGH treatment. The objectives of this study were to determine
      the efficacy of low-dose rhGH treatment for 4 weeks in malnourished elderly
      patients, its effect on physical functions, and the intermediate term outcome
      after a 4-week rhGH treatment. The study design was a randomized, placebo
      controlled, double-blind trial conducted in a university teaching hospital. The
      patients were 19 medically stable malnourished elderly subjects. Intervention in
      the rhGH group was as follows: rhGH (Saizen, Serono, Switzerland) 0.09 IU/kg body
      weight (BW) 3 times weekly were given together with appropriate dietary
      intervention as prescribed by the dietitian. In the placebo group, equal volumes
      of normal saline per kilogram BW were given 3 times weekly together with the
      dietary intervention. The baseline demographic, anthropometric, nutritional, and
      hematological variables, measures of physical function, and insulin-like growth
      factor I levels in both groups were comparable. Compared with the placebo group,
      the GH-treated group showed a more rapid gain in BW (after 3 weeks, +1.27 +/-
      0.36 vs. -0.28 +/- 0.37 kg; P = 0.008), total lean body mass (change after 3
      weeks by bio-impedance analysis, +1.45 +/- 0.36 vs. -0.37 +/- 0.48 kg; P = 0.009)
      and a faster improvement in 5-m walking time (decrease after 4 weeks, 23.79 +/-
      9.41 vs. 0.45 +/- 4.62 sec; P = 0.047). The hemoglobin level rose more in the
      rhGH than the placebo groups (change at 8 weeks, +0.84 +/- 0.34 vs. -0.42 +/-
      0.29 g/dL; P = 0.012). Serum albumin level also showed a greater delayed increase
      in the rhGH group than in the placebo group (change at 8 weeks, +5.1 +/- 0.8 vs.
      1.6 +/- 1.2 g/dL; P = 0.023). There was no statistically significant difference
      for other nutritional variables. There was a greater rise in the mean serum
      insulin-like growth factor I level at 4 weeks in the GH than in the placebo
      groups (197 +/- 58 vs. 54 +/- 26 U/L; P = 0.034). The improvement in the rhGH
      group gradually diminished on follow-up and became statistically insignificant 8
      weeks after stopping rhGH treatment. There were no GH-related adverse effects.
      Low-dose rhGH was an effective and safe adjuvant to dietary augmentation for
      stable malnourished elderly subjects. It led to a faster gain in total lean body
      mass, which was associated with greater improvement in walking speed when
      compared with dietary intervention alone. There were no apparent side effects.

PMID- 11344185
TI  - Plasma levels of agouti-related protein are increased in obese men.
AB  - To investigate the relationship between peripheral blood levels of agouti-related
      protein (AGRP) and various parameters of obesity, we measured the plasma level of
      AGRP in 15 obese and 15 nonobese men and evaluated its relationship with body
      mass index (BMI), body fat weight, and visceral, sc, and total fat areas measured
      by computed tomography, fasting insulin levels, glucose infusion rate during an
      euglycemic hyperinsulinemic clamp study, serum leptin, and plasma alpha-MSH.
      Obese men had significantly higher plasma concentrations of AGRP than nonobese
      men (P < 0.01). Univariate analysis showed that the plasma levels of AGRP are
      proportionally correlated with BMI, body fat weight, and sc fat area in obese men
      (BMI: r = 0.732, P < 0.01; body fat weight: r = 0.603, P < 0.02; sc fat area: r =
      0.668, P < 0.01) and in all men (BMI: r = 0.839, P < 0.0001; body fat weight: r =
      0.818, P < 0.0001; sc fat area: r = 0.728, P < 0.0001). In all men, the plasma
      levels of AGRP were significantly correlated with the visceral fat area (r =
      0.478, P < 0.01), total fat area (r = 0.655, P < 0.0001), fasting insulin level
      (r = 0.488, P < 0.01), glucose infusion rate (r = -0.564, P < 0.01), serum level
      of leptin (r = 0.661, P < 0.0001), and the plasma level of alpha-MSH (r = 0.556,
      P < 0.01). In all subjects, multiple regression analysis showed that the plasma
      levels of AGRP are significantly (F = 15.522, r = 0.801, P < 0.03) correlated
      with the plasma levels of alpha-MSH, independently from the total fat area.
      However, the correlation between plasma levels of AGRP and serum levels of leptin
      was found to be dependent on the total fat area. In brief, these findings showed
      that the circulating levels of AGRP are increased in obese men and that they are
      correlated with various parameters of obesity. Although correlation does not
      prove causation, the results of this study suggest that peripheral AGRP may play
      a role in the pathogenesis of obesity.

PMID- 11344186
TI  - Long-term outcome of interferon-alpha-induced thyroid autoimmunity and prognostic
      influence of thyroid autoantibody pattern at the end of treatment.
AB  - Thyroid autoimmunity and dysfunction have been widely reported as side effects of
      interferon-alpha (IFN-alpha) treatment, but the literature lacks data regarding
      the long-term course of these complications, clinical observation being limited
      to 6-12 months off therapy. Our study is the first that has aimed to evaluate the
      natural history of IFN-related thyroid autoimmunity during a 6.2-yr follow-up
      after the IFN-alpha withdrawal as well as to investigate the potential role of
      the autoantibody pattern at the end of treatment to predict the long-term
      outcome. Our study group included 114 patients (79 males, 35 females), mean age
      48 yr (range 23-67 yr) with no preexisting thyroid disease, undergoing a 12-month
      treatment with recombinant IFN-alpha for C virus-related chronic active
      hepatitis. Thyroid autoimmunity (serum TgAb and TPOAb) and function (serum FT(4),
      FT(3), TSH) were retrospectively evaluated at the end of IFN therapy, 6 months
      after IFN withdrawal and after a median period of 6.2 yr (range 5.5-8.4 yr). At
      the end of treatment, 78 patients were negative for thyroid autoantibodies (Abs-)
      and all but one of them remained so for the following evaluations. The remaining
      36 patients had thyroid autoantibodies (Abs+) at the end of treatment, and they
      subsequently showed a heterogeneous behavior: 16 patients remained Abs+ for the
      whole length of the study (persistent thyroiditis); 10 patients became Abs- 6
      months off therapy but were again Abs+ 6.2 yr later (remitting/relapsing
      thyroiditis); 10 patients reverted to autoantibody negativity at different
      observation times (transient thyroiditis). The absence of thyroid autoantibodies
      at the end of treatment was a protective factor for the successive development of
      thyroiditis (odds ratio: 0.02, confidence interval (CI) 95%: 0-0.1). On the
      contrary, the positivity for TgAb and/or TPOAb at high titers at the end of IFN
      treatment was significantly related to the highest risk of having chronic
      thyroiditis (odds ratio: 17.3, CI 95%: 3.2-91.7 for TgAb levels > 50 degree
      percentile; odds ratio: 7.3, CI 95%: 1.5-35.2 for TPOAb levels > 50 degree
      percentile). None of the patients showed overt thyroid dysfunction throughout the
      study, whereas a subclinical hypothyroidism was found in 12 patients. In all 12
      cases, the functional abnormality was accompanied by the presence of thyroid
      autoantibodies. Eight of these 12 patients belonged to the group with persistent
      thyroiditis (P < 0.05). The absence of thyroid autoantibodies at the end of
      treatment was a protective factor for the successive development of thyroid
      dysfunction (odds ratio: 0.06, CI 95%: 0.01-0.56). On the contrary, the
      positivity for both TgAb and TPOAb at the end of IFN therapy was significantly
      correlated with the highest risk of having subclinical hypothyroidism 6.2 yr.
      later (odds ratio: 38.7; CI 95%: 6.2-242). Our study demonstrates that in
      patients undergoing an IFN-alpha therapy for chronic hepatitis C and with no
      evidence of preexisting thyroid disease: 1) the negativity for thyroid
      autoantibodies after IFN treatment is a protective factor for the developing
      thyroid autoimmunity and/or dysfunction in following years; 2) the IFN-alpha
      related thyroid autoimmunity is not a complete reversible phenomenon because some
      patients can develop chronic thyroiditis; 3) high autoantibody levels at the end
      of IFN therapy are related to the risk of having chronic thyroid autoimmunity;
      and 4) the coexistence of TgAb and TPOAb at the end of treatment is a predictive
      factor for the presence of thyroid dysfunction, even if subclinical, many years
      after IFN withdrawal.

PMID- 11344187
TI  - Hypoadiponectinemia in obesity and type 2 diabetes: close association with
      insulin resistance and hyperinsulinemia.
AB  - Plasma concentrations of adiponectin, a novel adipose-specific protein with
      putative antiatherogenic and antiinflammatory effects, were found to be decreased
      in Japanese individuals with obesity, type 2 diabetes, and cardiovascular
      disease, conditions commonly associated with insulin resistance and
      hyperinsulinemia. To further characterize the relationship between
      adiponectinemia and adiposity, insulin sensitivity, insulinemia, and glucose
      tolerance, we measured plasma adiponectin concentrations, body composition (dual
      energy x-ray absorptiometry), insulin sensitivity (M, hyperinsulinemic clamp),
      and glucose tolerance (75-g oral glucose tolerance test) in 23 Caucasians and 121
      Pima Indians, a population with a high propensity for obesity and type 2
      diabetes. Plasma adiponectin concentration was negatively correlated with percent
      body fat (r = -0.43), waist-to-thigh ratio (r = -0.46), fasting plasma insulin
      concentration (r = -0.63), and 2-h glucose concentration (r = -0.38), and
      positively correlated with M (r = 0.59) (all P < 0.001); all relations were
      evident in both ethnic groups. In a multivariate analysis, fasting plasma insulin
      concentration, M, and waist-to-thigh ratio, but not percent body fat or 2-h
      glucose concentration, were significant independent determinates of
      adiponectinemia, explaining 47% of the variance (r(2) = 0.47). Differences in
      adiponectinemia between Pima Indians and Caucasians (7.2 +/- 2.6 vs. 10.2 +/- 4.3
      microg/ml, P < 0.0001) and between Pima Indians with normal, impaired, and
      diabetic glucose tolerance (7.5 +/- 2.7, 6.1 +/- 2.0, 5.5 +/- 1.6 microg/ml, P <
      0.0001) remained significant after adjustment for adiposity, but not after
      additional adjustment for M or fasting insulin concentration. These results
      confirm that obesity and type 2 diabetes are associated with low plasma
      adiponectin concentrations in different ethnic groups and indicate that the
      degree of hypoadiponectinemia is more closely related to the degree of insulin
      resistance and hyperinsulinemia than to the degree of adiposity and glucose
      intolerance.

PMID- 11344188
TI  - Early initiation of growth hormone treatment allows age-appropriate estrogen use
      in Turner's syndrome.
AB  - Because estrogen (E) accelerates skeletal maturation it can decrease final height
      attainable with GH therapy in girls with Turner's syndrome (TS). Nonetheless, as
      age-appropriate E administration does have psychobehavioral benefits for such
      patients, we asked whether E treatment in TS could occur without adverse impact
      on final adult height if GH therapy were started at an earlier age. Near adult
      height (NAH) was assessed in 344 girls with TS, who had received both GH and E
      and were followed in the National Cooperative Growth Study database. The groups
      were divided into quartiles based on age at initiation of GH (2-10, 10-12, 12-14,
      and 14-18 yr). The longest total and E-free period of GH treatment occurred in
      the girls who had started treatment in the youngest quartile (mean age, 8.2 +/-
      1.5 (SD) yr); they were also exposed to E at the youngest age (12.7 +/- 1.6 yr).
      Although the girls in the youngest group received E at an earlier age, they had a
      significantly greater increase (1.8 +/- 0.8) in Lyon height SD score at NAH over
      Lyon predicted adult height than those in the oldest GH-treated group (0.8 +/-
      0.6), which first received E at 15.9 +/- 1.3 yr. Multiple linear regression
      equations for gain in Lyon height SD score and in height (cm) showed greater
      increments with a longer period of E-free GH therapy. All four GH age groups had
      the same NAH, but the youngest quartile was youngest at NAH and likely still
      having more growth potential. Comparable data were found in 127 TS girls with
      spontaneous puberty. In conclusion, girls with TS starting GH at an early age
      have a greater gain in Lyon SD score at NAH compared with those starting later,
      even though they received E at a younger age. If GH therapy were started early, E
      treatment could be initiated at a younger, more age-appropriate time without
      compromising adult height.

PMID- 11344189
TI  - Use of the ligand immunofunctional assay for human insulin-like growth factor
      ((IGF) binding protein-3 (IGFBP-3) to analyze IGFBP-3 proteolysis and igf-i
      bioavailability in healthy adults, GH-deficient and acromegalic patients, and
      diabetics.
AB  - The ligand immunofunctional assay for plasma insulin-like growth factor (IGF)
      binding protein (IGFBP)-3 developed in our laboratory provides for specific
      measurement of intact, as opposed to proteolyzed, IGFBP-3. IGFBP-bound IGFs are
      dissociated and separated by acid pH ultrafiltration; thereafter, intact and
      proteolyzed IGFBP-3 are captured by a monoclonal antibody in a solid-phase assay
      and incubated with (125)I-IGF-I, which detects the intact protein but not its
      proteolytic fragments. This assay was combined with assays for IGF-I (RIA of the
      ultrafiltrate) and total IGFBP-3 (immunoradiometric assay) to quantify the
      percentage of proteolyzed IGFBP-3 (percent proteolyzed IGFBP-3) and to calculate
      the IGF-I/intact IGFBP-3 ratio as an index of the fraction of exchangeable IGF-I
      bound to IGFBP-3. This fraction represents most of the IGF-I that is
      bioavailable. Because GH and insulin control the hepatic production and plasma
      concentrations of IGF-I and IGFBP-3, we set out to determine whether variations
      in the secretion of the two hormones are involved in the regulation of IGFBP-3
      proteolysis. The study included adult populations of 36 healthy subjects, 23
      hypopituitary patients untreated with GH, 43 acromegalics (13 untreated), 42
      insulin-treated type 1 diabetics [insulin-dependent diabetes mellitus (IDDM)]
      patients, and 50 type 2 diabetics [non-IDDM (NIDDM)] patients, 22 of whom were
      insulin-treated and the remaining 28 treated with sulfonylurea and/or metformin).
      Unlike IGF-I and (to a lesser extent) total IGFBP-3 levels, which decline with
      age, percent proteolyzed IGFBP-3 seemed relatively stable. In healthy adults, the
      mean +/- SEM was 29.4 +/- 1.9 for subjects less than 45 yr old and was slightly
      (but not significantly) lower, 25.7 +/- 3, for those of more than 45 yr. There
      was no difference between male and female subjects. In GH-deficient patients,
      despite severely depressed IGF-I levels, percent proteolyzed IGFBP-3 and IGF
      I/intact IGFBP-3 ratios were within the normal range. Among acromegalics, percent
      proteolyzed IGFBP-3 was elevated: 36.6 +/- 3.3 for patients of less than 45 yr,
      33.3 +/- 3.2 for patients of more than 45 yr (P = 0.02 vs. healthy subjects).
      Consequently, the effects of excessive IGF-I synthesis are exacerbated by the
      enlarged exchangeable fraction of IGFBP-3-bound IGF-I. There was no significant
      difference in percent proteolyzed IGFBP-3 between GH-deficient patients before
      and after GH treatment or between treated and untreated acromegalics. In IDDM
      patients, the means for percent proteolyzed IGFBP-3 were higher than those in
      healthy adults: 36.7 +/- 3.7 (P = 0.03) and 31.3 +/- 3.3 for subjects of less
      than 45 and more than 45 yr, respectively. In NIDDM patients, all of whom were
      more than 45 yr old, the means were 35.2 +/- 2.5 (P = 0.02) for insulin-treated
      patients and 33 +/- 2.5 for the group treated orally. Among the diabetics,
      increased IGFBP-3 proteolysis resulted in an IGF-I/intact IGFBP-3 ratio that was
      normal for IDDM patients of less than 45 yr and above normal (P = 0.01) for the
      others. Percentage proteolyzed IGFBP-3 and the IGF-I/intact IGFBP-3 ratio were
      inversely related to body mass index in IDDM patients (r = -0.42, P = 0.008; and
      r = -0.31, P = 0.05, respectively) and to percentage glycosylated hemoglobin in
      all insulin-treated diabetics (r = -0.25, P = 0.05; and r = -0.33, P = 0.008,
      respectively). There was also an inverse relationship between IGF-I/intact IGFBP
      3 ratios and IGFBP-1 levels in healthy adults (r = -0.39, P = 0.03) and orally
      treated NIDDM patients (r = -0.37, P = 0.05). Percentage proteolyzed IGFBP-3 was
      positively correlated to total IGFBP-3 in healthy adults (r = 0.65, P = 0.0001)
      and in all the groups of patients. It was negatively correlated to IGF-I/total
      IGFBP-3 in healthy subjects (r = -0.40, P = 0.02) and diabetics (r = -0.30, P =
      0.005). This suggests an autoregulatory mechanism controlling the bioavailability
      of IGFBP-3-bound IGF-I in the 140-kDa complexes. In the pathological conditions
      studied here, regulation of IGF-I bioavailability by limited proteolysis of IGFBP
      3 contributes toward an appropriate adaptation to insulin deficiency and/or
      resistance but not to disturbances of GH secretion.

PMID- 11344190
TI  - Growth hormone therapy and growth in children with Noonan's syndrome: results of
      3 years' follow-up.
AB  - Growth data from the first 3 yr of a multicenter study examining the efficacy and
      safety of recombinant human GH [rhGH; 4 IU (1.3 mg)/m(2).day, sc] in children
      with Noonan's syndrome (NS) are reported for 23 subjects. Sixteen male and seven
      female patients (age, 9.3 +/- 2.6 yr at onset of GH therapy, mean +/- SD; range,
      4.8-13.7) were each assessed at 1, 2, and 3 yr after starting treatment.
      Comparisons were made with a group of eight subjects (six males and two females,
      age, 9.0 +/- 4.1 yr; range, 4.1-14.8) with NS, not treated with rhGH, measured
      over the same period. All treated subjects underwent annual cardiac assessment.
      Height SD score increased from -2.7 +/- 0.4 at the start of GH therapy to -1.9 +/
      0.9 3 yr later (P < 0.001, two-tailed t test). This corresponded to an increase
      in height from 116.1 +/- 13.2 to 137.3 +/- 14.0 cm. Height velocity increased
      from 4.4 +/- 1.7 cm/yr in the year before treatment to 8.4 +/- 1.7 (P < 0.001),
      6.2 +/- 1.7 (P < 0.001), and 5.8 +/- 1.8 (P = 0.01, two-tailed t test compared
      with baseline) during the first, second, and third years of GH treatment,
      respectively. Height acceleration was not significant during the second or third
      years when pubertal subjects were excluded. The comparison group showed an
      increase in height from 116.0 +/- 19.8 to 131.9 +/- 21.1 cm over the 3 yr (height
      SD score, -2.7 +/- 0.6 to -2.4 +/- 0.7, P = 0.3). None of the 23 children
      developed hypertrophic cardiomyopathy during GH treatment. The increase in growth
      rate in NS resulting from 1 yr of GH therapy seems to be maintained during the
      second year, although height velocity shows a less significant increase over
      pretherapy values. Possible abnormal anabolic effects of rhGH on myocardial
      thickness were not confirmed, and no treated patient developed features of
      hypertrophic cardiomyopathy.

PMID- 11344191
TI  - Blunted vascular and renal effects of exogenous atrial natriuretic peptide in
      patients with cushing's disease.
AB  - The role of atrial natriuretic peptide (ANP) in glucocorticoid hypertension is
      still controversial, as glucocorticoids enhance the secretion of ANP in vivo, but
      reduce its biological activity in vitro. In isolated cells, for example, the cGMP
      response to ANP is suppressed by dexamethasone. We tested the in vivo relevance
      of this observation by comparing the cGMP, endocrine, and renal responses to
      exogenous ANP in patients with Cushing's disease (CD; n = 10) and in a matched
      group of essential hypertensives (EH; n = 8) and normotensive controls (N; n =
      4). alpha-human-ANP was infused at 0.01 microg/kg/min for 120 min with a 30-min
      recovery period; hormonal and arterial pressure measurements were performed at 30
      min intervals, and renal parameters were measured at baseline and after infusion.
      There was a 4-fold increase in plasma ANP in all groups, but the increments in
      plasma cGMP were about 50% lower in CD than in N and EH; urinary cGMP was
      similarly lower in CD (247 +/- 61 vs. 529 +/- 146 and 384 +/- 54 nmol/150 min,
      respectively). This was associated with a reduced peak increase in hematocrit in
      CD (+2.6 +/- 0.9%) compared with N (+6.6 +/- 0.9%) and EH (+7.1 +/- 0.7%; P <
      0.05 CD vs. both); the diuretic and natriuretic effects of ANP were also lower in
      CD than in EH with very similar systemic pressure levels (382 +/- 63 vs. 848 +/-
      130 mL/150 min, and 61 +/- 14 vs. 113 +/- 14 mmol/150 min, respectively; P < 0.05
      for both). The increments in plasma and urinary cGMP in response to physiological
      doses of ANP are thus blunted in CD patients compared with those in N and EH.
      This biochemical defect is associated with reduced capillary permeability and a
      lesser diuretic and natriuretic effect. These data are compatible with an
      impairment of the biological activity of ANP in glucocorticoid hypertension in
      humans.

PMID- 11344192
TI  - In vivo evidence for the role of lipoprotein lipase activity in the regulation of
      apolipoprotein AI metabolism: a kinetic study in control subjects and patients
      with type II diabetes mellitus.
AB  - The aim of this study was to delineate the role of lipoprotein lipase (LPL)
      activity in the kinetic alterations of high density lipoprotein (HDL) metabolism
      in patients with type II diabetes mellitus compared with controls. The kinetics
      of HDL were studied by endogenous labeling of HDL apolipoprotein AI (HDL-apo AI)
      using a primed infusion of D(3)-leucine. The HDL-apo AI fractional catabolic rate
      (FCR) was significantly increased (0.32 +/- 0.07 vs. 0.23 +/- 0.05 pool/day; P <
      0.01), and HDL composition was changed [HDL cholesterol, 0.77 +/- 0.16 vs. 1.19
      +/- 0.37 mmol/L (P < 0.05); HDL triglycerides, 0.19 +/- 0.12 vs. 0.10 +/- 0.03
      mmol/L (P < 0.05)] in diabetic patients compared with healthy subjects. HDL-apo
      AI FCR was correlated to plasma and HDL triglyceride concentrations (r = 0.82; P
      < 0.05 and r = 0.80; P < 0.05, respectively) and to homeostasis model assessment
      (r = 0.78; P < 0.05). Postheparin plasma LPL activity was decreased in type II
      diabetes (6.8 +/- 2.8 vs. 18.1 +/- 5.2 micromol/mL postheparin plasma.h; P <
      0.005) compared with that in healthy subjects and was correlated to the FCR of
      HDL-apo AI (r = -0.63; P < 0.05). LPL activity was also correlated with HDL
      cholesterol (r = 0.78; P < 0.05), plasma and HDL triglycerides (r = -0.87; P <
      0.005 and r = -0.83; P < 0.05, respectively), and homeostasis model assessment (r
      = -0.79; P < 0.05). In addition, the LPL to hepatic lipase ratio was correlated
      with the catabolic rate of HDL (r = -0.76; P < 0.06). These results suggest that
      a decrease in the LPL to hepatic lipase ratio in type II diabetes mellitus,
      mainly related to lowered LPL activity, could induce an increase in HDL
      catabolism. These alterations in HDL kinetics in type II diabetes proceed to some
      extent from changes in their composition, probably linked to an increase in
      triglyceride transfer from very low density lipoprotein particles, in close
      relationship with LPL activity and resistance to insulin.

PMID- 11344193
TI  - Dehydroepiandrosterone replacement in women with adrenal insufficiency: effects
      on body composition, serum leptin, bone turnover, and exercise capacity.
AB  - Studies in animals and humans using supraphysiological doses of
      dehydroepiandrosterone (DHEA) reported significant changes in body composition
      and carbohydrate metabolism. To investigate the metabolic action of a
      physiological DHEA replacement dose, we studied 24 women with adrenal
      insufficiency (AI; mean +/- SD age, 42.3 +/- 9.3 yr; duration of disease, 9.2 +/-
      8.4 yr; body mass index, 23.4 +/- 4.0 kg/m(2)) in a double blind, placebo
      controlled, randomized, cross-over design. They received 50 mg DHEA/day and
      placebo orally for 4 months each, with a 1 -month washout period. Measurements
      included fasting serum glucose, insulin, leptin, bone markers, anthropometric
      parameters determined by bioimpedance analysis, and exercise capacity as assessed
      by an incremental cycling test. DHEA did not induce any change in body mass index
      (placebo vs. DHEA, 23.3 +/- 4.1 vs. 23.2 +/- 3.9 kg/m(2); P = 0.39), parameters
      of body composition, or exercise capacity. However, compared with placebo, DHEA
      replacement led to a significant decrease in serum leptin (absolute change after
      4 months, DHEA vs. placebo, -5.3 +/- 8.0 vs. 1.1 +/- 5.7 ng/mL; P = 0.01). This
      is most likely the result of the DHEA-induced normalization of circulating
      androgens. DHEA had no effect on fasting glucose, insulin, or the glucose/insulin
      ratio. Compared with placebo, serum osteocalcin increased slightly, but
      significantly, during DHEA treatment (absolute change after 4 months DHEA vs.
      placebo, +1.6 +/- 5.3 vs. -1.2 +/- 6.2 ng/mL; P = 0.02). However, urinary cross
      links excretion did not change. In conclusion, replacement of DHEA in a
      physiological dose in patients with pathological DHEA deficiency does not have a
      significant effect on carbohydrate metabolism, body composition, or exercise
      capacity. The biological relevance of the changes in leptin and osteocalcin
      levels remains to be determined.

PMID- 11344194
TI  - Blood growth hormone-binding protein levels in premenopausal and postmenopausal
      women: roles of body weight and estrogen levels.
AB  - A substantial proportion of GH circulates bound to high affinity GH-binding
      protein (GHBP), which corresponds to the extracellular domain of the GH receptor.
      Current evidence indicates that nutritional status has an important role in
      regulating plasma GHBP levels in humans. In the present study the relationship
      among plasma GHBP levels, body composition [by bioelectrical impedance analysis
      (BIA) and dual energy x-ray absorptiometry (DEXA)] and serum estradiol (E(2)) was
      evaluated in premenopausal (n = 92) and postmenopausal (n = 118) healthy women
      with different body weight [three groups according to body mass index (BMI):
      normal, 18.5-24.99; overweight, 25-29.99; obese, 30-39.99 kg/m(2)]. Plasma GHBP
      levels were measured by high pressure liquid chromatography gel filtration. GH
      and insulin-like growth factor I levels were determined by immunoradiometric
      assay and RIA, respectively. GHBP levels were significantly higher in
      premenopausal women with BMI above 25 kg/m(2) (overweight, 3.789 +/- 0.306
      nmol/L; obese, 4.372 +/- 0.431 nmol/L) than those observed in postmenopausal
      women (overweight, 1.425 +/- 0.09 nmol/L; obese, 1.506 +/- 0.177 nmol/L). No
      significant differences were found between normal weight premenopausal (1.741 +/-
      0.104 nmol/L) and postmenopausal (1.524 +/- 0.202 nmol/L) women. In premenopausal
      women GHBP levels correlated positively with BMI (r = 0.675; P < 0.001), fat mass
      (FM; r = 0.782; P < 0.001; by BIA; r = 0.776; P < 0.001; by DEXA), truncal fat
      (TF; r = 0.682; P < 0.001), waist to hip circumference ratio (WHR; r = 0.551; P <
      0.001), and E(2) (r = 0.298; P < 0.05), whereas no significant correlation was
      found in postmenopausal women between GHBP levels and BMI, FM, TF, WHR, or E(2).
      In normal weight pre- and postmenopausal women GHBP levels did not change between
      the ages of 20 and 69 yr. No statistically significant correlation was found
      between GHBP and age for all groups studied. Moreover, in two distinct subgroups
      of pre- and postmenopausal women, aged 40-49 yr, the direct relationship between
      GHBP levels and all indexes of adiposity were only observed in premenopausal
      women [BMI: r = 0.836; P < 0.001; FM: r = 0.745 (BIA) and r = 0.832 (DEXA); P <
      0.001; TF: r = 0.782; P < 0.001; WHR: r = 0.551; P < 0.05], but not in
      postmenopausal women. In conclusion, the present data indicate a strong direct
      correlation between GHBP and body fat in premenopausal, but not in postmenopausal
      women, whereas they failed to detect a relationship between GHBP and age.
      Therefore, these results suggest that endogenous estrogen status may be an
      important determinant of the changes in GHBP levels in women with different body
      weights.

PMID- 11344195
TI  - The role of the liver in the acute effect of alcohol on androgens in women.
AB  - The hypothalamic-pituitary-gonadal and -adrenal axes are regarded as the main
      sites of the actions of alcohol on steroids. In the present study the effect of
      alcohol (0.4-0.5 g/kg, orally) on venous plasma and urinary androgens was
      investigated in 21 premenopausal women using oral contraceptives as well as in 10
      premenopausal nonusers. After intake of alcohol, an acute elevation in plasma
      testosterone, a decline in androstenedione levels, and an elevation in the ratio
      of testosterone to androstenedione were observed in both groups. The effects
      lasted throughout the period of ethanol elimination and were abolished during
      pretreatment with 4-methylpyrazole (10-15 mg/kg, orally). The acute effects were
      higher in the group using oral contraceptives than in the nonusers. The
      testosterone effect in plasma was reflected in the free testosterone fraction. A
      decline in urinary androsterone and etiocholanolone levels, the principal
      catabolic products of androgens, was observed during alcohol intoxication. In
      conclusion, the present acute effects on plasma and urinary steroid hormones seem
      to be explained by an inhibited catabolism mediated by the alcohol-induced change
      in the redox state in the liver. Our results suggests that the liver should be
      included as a major site in the acute endocrinological effects of alcohol on
      steroid hormones in women.

PMID- 11344196
TI  - Blood-brain barrier transport and brain metabolism of glucose during acute
      hyperglycemia in humans.
AB  - It is controversial whether transport adaptation takes place in chronic or acute
      hyperglycemia. Blood-brain barrier glucose permeability and regional brain
      glucose metabolism (CMR(glc)) was studied in acute hyperglycemia in six normal
      human subjects (mean age, 23 yr) using the double indicator method and positron
      emission tomography and [(18)F]fluorodeoxyglucose as tracer. The Kety-Schmidt
      technique was used for measurement of cerebral blood flow (CBF). After 2 h of
      hyperglycemia (15.7 +/- 0.7 mmol/L), the glucose permeability-surface area
      product from blood to brain remained unchanged (0.050 +/- 0.008 vs. 0.059 +/-
      0.031 mL/100 g.min). The unidirectional clearance of [(18)F]fluorodeoxyglucose
      (K(1)*) was reduced from 0.108 +/- 0.011 to 0.061 +/- 0.005 mL/100 g.min (P <
      0.0004). During hyperglycemia, global CMR(glc) remained constant (21.4 +/- 1.2
      vs. 23.1 +/- 2.2 micromol/100 g.min, normo- and hyperglycemia, respectively).
      Except for a significant increase in white matter CMR(glc), no regional
      difference in CMR(glc) was found. Likewise, CBF remained unchanged. The reduction
      in K(1)* was compatible with Michaelis-Menten kinetics for facilitated transport.
      Our findings indicate no major adaptational changes in the maximal transport
      velocity or affinity to the blood-brain barrier glucose transporter. Finally,
      hyperglycemia did not change global CBF or CMR(glc).

PMID- 11344197
TI  - Peripheral administration of human corticotropin-releasing hormone: a novel
      method to increase energy expenditure and fat oxidation in man.
AB  - CRH increases energy expenditure and decreases food intake in experimental
      animals. We proposed the hypothesis that peripheral administration of CRH might
      increase energy expenditure in human subjects. Four men and four women (age, 19
      39 yr) were randomized to a double blind, cross-over trial to test the effect of
      human CRH (hCRH), ovine CRH (oCRH), and placebo on resting energy expenditure
      measured by indirect calorimetry. CRH was administered by primed continuous
      infusion at progressively increasing doses of 0.5, 1.0, and 2.0 microg/kg.h at 2
      h intervals. hCRH increased resting energy expenditure by 13.9% at the end of the
      infusion. Respiratory quotient fell from 0.828 to 0.768 during the hCRH infusion
      compared with a fall from 0.836 to 0.807 during placebo infusion (P < 0.05). Fat
      oxidation increased by 55% compared with placebo at the highest dose of hCRH.
      Heart rate increased during hCRH to 10.7 bpm higher than placebo (P < 0.05). oCRH
      did not increase heart rate. oCRH also had no significant effect on respiratory
      quotient, and only a small effect on energy expenditure. During hCRH infusion,
      venous plasma epinephrine, norepinephrine, glycerol, and nonesterified fatty acid
      levels were not significantly different from those during placebo treatment.
      Peripheral CRH administration offers a novel strategy to increase energy
      expenditure.

PMID- 11344198
TI  - Pheochromocytomas in von Hippel-Lindau syndrome and multiple endocrine neoplasia
      type 2 display distinct biochemical and clinical phenotypes.
AB  - This study examined the mechanisms linking different biochemical and clinical
      phenotypes of pheochromocytoma in multiple endocrine neoplasia type 2 (MEN 2) and
      von Hippel-Lindau (VHL) syndrome to underlying differences in the expression of
      tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine synthesis,
      and of phenylethanolamine N-methyltransferase (PNMT), the enzyme that converts
      norepinephrine to epinephrine. Signs and symptoms of pheochromocytoma, plasma
      catecholamines and metanephrines, and tumor cell neurochemistry and expression of
      TH and PNMT were examined in 19 MEN 2 patients and 30 VHL patients with adrenal
      pheochromocytomas. MEN 2 patients were more symptomatic and had a higher
      incidence of hypertension (mainly paroxysmal) and higher plasma concentrations of
      metanephrines, but paradoxically lower total plasma concentrations of
      catecholamines, than VHL patients. MEN 2 patients all had elevated plasma
      concentrations of the epinephrine metabolite, metanephrine, whereas VHL patients
      showed specific increases in the norepinephrine metabolite, normetanephrine. The
      above differences in clinical presentation were largely explained by lower total
      tissue contents of catecholamines and expression of TH and negligible stores of
      epinephrine and expression of PNMT in pheochromocytomas from VHL than from MEN 2
      patients. Thus, mutation-dependent differences in the expression of genes
      controlling catecholamine synthesis represent molecular mechanisms linking the
      underlying mutation to differences in clinical presentation of pheochromocytoma
      in patients with MEN 2 and the VHL syndrome.

PMID- 11344199
TI  - Nineteen years of national screening for congenital hypothyroidism: familial
      cases with thyroid dysgenesis suggest the involvement of genetic factors.
AB  - Although a few familial forms of congenital hypothyroidism (CH) due to thyroid
      dysgenesis (TD) have been reported, this disorder is usually considered to be
      sporadic. Recently, we reported that 2% of CH patients with TD have a positive
      familial history. The aim of this study was to describe the clinical
      characteristics of these familial cases and to compare them with sporadic cases.
      We used the French national population-based registry of the first 19-yr
      screening program, which included 14,416,428 screened neonates with a 100%
      recovery rate. Familial history of CH with TD was investigated by means of a
      questionnaire sent to the pediatricians (n = 592) who provided ongoing clinical
      care for the 4049 CH patients detected during this period, including 2863 CH
      cases due to TD. Information was obtained from 73% of these pediatricians who
      were following up 2472 CH patients with TD (86%). In all, 67 patients with a
      positive family history of CH with TD were referred, belonging to 32 multiplex
      families (i.e. including at least 2 affected members). Families were identified
      with ectopic gland (n = 12), athyreosis (n = 7), or both (n = 13). Comparison of
      familial with isolated cases showed a similar etiological diagnosis distribution
      of CH (40% vs. 33% for athyreosis and 60% vs. 67% for ectopic thyroid gland,
      respectively), whereas a significantly lower predominance of females was found in
      familial than in isolated cases (1.4 vs. 2.7; P < 0.03). Extrathyroidal
      congenital malformations were found with a similarly higher incidence in familial
      and isolated CH populations compared with the general population (respectively,
      9% and 8.2% vs. 2.5%). In conclusion, although familial cases represent a
      minority of cases of congenital hypothyroidism caused by thyroid dysgenesis, they
      were observed in a significantly higher proportion (>15-fold) than would be
      expected from chance alone. This familial clustering, including athyreosis and
      ectopic thyroid gland, strongly suggests that genetic factors could be involved
      in thyroid dysgenesis with a common underlying mechanism for both etiological
      groups. Moreover, the high proportion of extrathyroidal congenital malformations
      in a population affected by CH due to TD suggests that the potential genetic
      factors involved in thyroid gland organogenesis are also involved in the
      development of other organs.

PMID- 11344200
TI  - Glucose-dependent insulinotropic hormone potentiates the hypoglycemic effect of
      glibenclamide in healthy volunteers: evidence for an effect on insulin
      extraction.
AB  - Glucose-dependent insulinotropic hormone (GIP) is an intestinal hormone
      considered to be an important mediator of the incretin effect, i.e. the augmented
      insulin release observed in response to orally, compared with iv, administered
      glucose, despite isoglycemic glucose profiles. Stimulation of beta-cell secretion
      of insulin by GIP is seen both in vitro and in vivo at permissive extracellular
      glucose concentrations (> 6 mmol/L). It has also been claimed that part of the
      incretin effect is due to decreased insulin extraction. We now show that an
      infusion of GIP in healthy volunteers in whom blood glucose levels were
      maintained at 5 mmol/L, increased glibenclamide-stimulated levels of plasma
      insulin without significantly changing the C peptide profile. The increased
      plasma insulin levels necessitated extra glucose infusion to maintain euglycemia,
      demonstrating the biological significance of the elevated insulin levels.
      Infusion of GIP alone caused neither glucose changes nor elevation of C peptide
      or insulin levels. Hence, our results show that at a blood glucose concentration
      of 5 mmol/L, GIP augments the increase in plasma insulin levels stimulated by
      glibenclamide, possibly acting through a mechanism involving decreased insulin
      extraction in the liver or peripheral tissues, thus increasing insulin
      availability.

PMID- 11344201
TI  - Osteopenia in eugonadal men with acquired immune deficiency syndrome wasting
      syndrome.
AB  - Multiple endocrine and metabolic consequences of human immunodeficiency virus
      (HIV) infection exist that may contribute to bone loss in men with the acquired
      immune deficiency syndrome (AIDS) wasting syndrome. Recent studies suggest that
      anabolic strategies can increase lean body mass in men with AIDS wasting. Prior
      studies have not examined the effects of anabolic agents on bone mineral density
      (BMD) or bone turnover in these men. To determine the effects of testosterone and
      progressive resistance training on BMD and bone turnover in eugonadal men with
      AIDS wasting, we randomly assigned 54 eugonadal men with AIDS wasting (weight <
      90% IBW or weight loss >10% from preillness baseline) to receive either
      testosterone enanthate (200 mg/week, im) or placebo and to progressive resistance
      training (3 times/week) or no training in a 2 x 2 factorial study design for 3
      months. The BMD of the lumbar spine, proximal femur, and total body; lean body
      mass; and fat mass were measured by dual energy x-ray absorptiometry. Total body
      scans were repeated after 12 weeks of therapy. Baseline bone turnover and BMD
      were compared with those in 35 age-matched healthy non-HIV-infected control
      subjects. Compared with controls, lumbar spine BMD (1.021 +/- 0.018 vs. 1.084 +/-
      0.025 g/cm(2); P = 0.04) and total hip BMD (0.951 +/- 0.017 vs. 1.070 +/- 0.019
      g/cm(2); P < 0.0001) were reduced in men with AIDS wasting. T-scores were lower
      in men with AIDS wasting at the lumbar spine (-0.62 +/- 0.17 vs. -0.07 +/- 0.23,
      P = 0.05) and total hip (-0.65 +/- 0.11 vs. +0.20 +/- 0.014, P < 0.0001). Total
      hip T scores were less than -1.0 in 33% of men with AIDS wasting. Neither the use
      of protease inhibitors nor the duration of protease inhibitors use correlated
      with BMD. Serum osteocalcin levels were lower (3.63 +/- 0.29 vs. 4.54 +/- 0.31
      nmol/L; P < 0.04) and urinary N-telopeptide excretion was higher (45.4 +/- 4.5
      vs. 26.8 +/- 3.0 nmol BCE/mmol creatinine; P = 0.004) in men with AIDS wasting
      than in controls. Lumbar spine BMD, as assessed on regional total body dual
      energy x-ray absorptiometry scan, increased over the 12-week treatment period in
      response to testosterone (+2.4 +/- 1.3 vs. -1.3 +/- 1.0%, testosterone vs.
      placebo, respectively; P = 0.02), but not in response to training (+0.8 +/- 1.0
      vs. +0.4 +/- 1.3%, training vs. no training; P = 0.70). Lumbar spine and total
      hip BMD are reduced in eugonadal men with AIDS wasting. Biochemical markers of
      bone turnover suggest that bone formation and bone resorption are uncoupled in
      these men. Testosterone administration, but not resistance training, over 3
      months increases lumbar spine BMD in eugonadal men with AIDS wasting.

PMID- 11344202
TI  - Heritability of insulin secretion and insulin action in women with polycystic
      ovary syndrome and their first degree relatives.
AB  - Polycystic ovary syndrome (PCOS), one of the most common endocrine disorders of
      reproductive age women, is associated with an increased risk of type 2 diabetes
      mellitus. Defects in both insulin action and insulin secretion contribute to this
      predisposition to diabetes, but the extent to which these defects are heritable
      among PCOS families has not been examined. In the present study we used the
      frequently sampled iv glucose tolerance test to quantitate insulin secretion
      (AIRg), insulin action (Si), and their product (AIRg x Si) among women with PCOS
      (n = 33) and their nondiabetic first degree relatives (n = 48). We then
      quantitated the heritability of these measures from familial correlations
      estimated within a genetic model. Familial (spousal, rhoMF; parent-offspring,
      rhoPO; and sibling, rhoSS) correlations were derived for log-transformed body
      mass index (BMI) as well as for AIRg, Si, and AIRg x Si, the latter three of
      which were adjusted for BMI. There was no evidence of significant heritability
      for either lnBMI or lnSi in these families. In contrast, the sibling correlation
      (rhoSS = 0.74) for lnAIRg was highly significant (chi(2) = 7.65; 1 df; P =
      0.006). In addition, the parameter quantitating insulin secretion in relation to
      insulin sensitivity [i.e. ln(AIRg x Si)] was significant among siblings (rho(SS)
      = 0.74; chi(2) = 4.32; 1 df; P = 0.04). In summary, the results of the present
      study indicate that there is an heritable component to beta-cell dysfunction in
      families of women with PCOS. We conclude that heritability of beta-cell
      dysfunction is likely to be a significant factor in the predisposition to
      diabetes in PCOS.

PMID- 11344203
TI  - Serum interleukin 6 is a major predictor of bone loss in women specific to the
      first decade past menopause.
AB  - The role of serum interleukin 6 (IL-6) as a predictor of bone loss was examined
      in a population-based, longitudinal study of 137 postmenopausal German women, 52
      80 yr old at baseline. Serum IL-6 and other biochemical parameters were measured
      in baseline blood or urine specimens. Repeat standardized measures of bone
      mineral density (BMD) at the femur (total hip) and the lumbar spine (L2-L4) were
      taken by dual x-ray absorptiometry an average of 3.3 yr apart. Medical history
      and anthropometric measures were obtained from standardized interview and
      examination. Crude and age-adjusted mean serum IL-6 levels were significantly
      lower in postmenopausal women with than without hormone replacement therapy at
      baseline. Among nonusers of hormone replacement therapy, serum IL-6
      concentrations were highly predictive of femoral bone loss, independently of
      potential confounders and plasma sex hormones. Statistical interaction between
      serum IL-6 and menopausal age or menopausal age group (>10 vs. < or =10 yr)
      indicated that the effect of IL-6 on bone loss weakened with increasing distance
      from menopause and was no longer significant in women more than 10 yr after
      menopause. Among women up to 10 yr past menopause (n = 39), serum IL-6 was the
      single most important predictor of femoral bone loss, accounting for up to 34% of
      the total variability of change in BMD. The unadjusted linear model predicted an
      annual 1.34% (95% confidence interval, 0.67-2.01) decrease in total hip BMD per
      log unit increase in serum IL-6. A similar, although nonsignificant, effect of
      serum IL-6 on vertebral bone loss was restricted to women within the first 6 yr
      after menopause (n = 18). These epidemiological data show that serum IL-6 is a
      predictor of postmenopausal bone loss, and that the effect appears to be most
      relevant through the first postmenopausal decade. Whether these findings reflect
      pathogenetic differences between early and postmenopausal bone loss, and whether
      serum IL-6 also predicts fracture risk need further elucidation.

PMID- 11344204
TI  - Effects of morning hypoglycemia on neuroendocrine and metabolic responses to
      subsequent afternoon hypoglycemia in normal man.
AB  - There is general agreement that prior hypoglycemia blunts subsequent hypoglycemic
      counterregulatory responses. However, there is considerable debate concerning the
      timing and number of prior hypoglycemic episodes required to cause this blunting
      effect. The aim of this study was to determine whether one episode of
      hypoglycemia could modify neuroendocrine, metabolic, and symptom responses to
      hypoglycemia induced 2 h later. A total of 24 (12 male and 12 female) young,
      healthy, overnight-fasted subjects participated in a series of glucose clamp
      studies. A total of 16 individuals underwent 2 randomized studies of either
      identical 2-h morning and afternoon hyperinsulinemic (490 +/- 60 pmol/L)
      hypoglycemia (2.9 +/- 0.1 mmol/L) separated by 2 h or, at least 2 months later, 2
      h morning and afternoon hyperinsulinemic (492 +/- 45 pmol/L) euglycemia (5.1 +/-
      0.1 mmol/L). A total of 8 other subjects participated in a single experiment that
      consisted of 2-h morning hyperinsulinemic (516 +/- 60 pmol/L) euglycemia (5.1 +/-
      0.1 mmol/L) and 2-h afternoon hyperinsulinemic (528 +/- 66 pmol/L) hypoglycemia
      (2.9 +/- 0.1 mmol/L) also separated by 2 h. Morning hypoglycemia significantly (P
      < 0.01) reduced (33-55%) the responses of epinephrine, norepinephrine, glucagon,
      GH, cortisol, and pancreatic polypeptide during afternoon hypoglycemia.
      Hypoglycemic symptoms (primarily neuroglycopenic) were also significantly (P <
      0.01) reduced during afternoon hypoglycemia. Plasma glucose, insulin,
      nonesterified fatty acids, glycerol, lactate, beta-hydroxybutyrate (P < 0.01),
      GH, and cortisol (P < 0.05) levels were significantly increased at the start of
      afternoon hypoglycemia following morning hypoglycemia. Morning hypoglycemia
      created an insulin-resistant state during afternoon hypoglycemia. Despite blunted
      neuroendocrine responses, glucose infusion rates required to maintain
      hypoglycemia and increases in glucose oxidation were significantly attenuated
      during afternoon compared with morning hypoglycemia. This was in marked contrast
      to euglycemic control experiments where glucose infusion rates and nonoxidative
      glucose disposal were significantly increased during afternoon relative to
      morning studies. We conclude that in normal man one episode of prolonged,
      moderate, morning hypoglycemia can produce substantial blunting of neuroendocrine
      and symptomatic responses to subsequent near-term hypoglycemia, and the induction
      of posthypoglycemic insulin resistance can compensate for blunted neuroendocrine
      responses by limiting glucose flux and specifically glucose oxidation during
      subsequent near-term hypoglycemia.

PMID- 11344205
TI  - Loss of estrogen receptor beta expression in malignant human prostate cells in
      primary cultures and in prostate cancer tissues.
AB  - The aim of this study was to investigate the expression of estrogen receptor (ER)
      beta and alpha genes in normal (N) and malignant (C) primary cultures of human
      prostate epithelial cells (PEC) and fibroblasts (PFC) and in the prostate tissue
      donors. Both ERbeta and ERalpha messenger ribonucleic acids were found by RT-PCR
      analysis in six NPECs and normal prostate tissues and in only one of six CPECs
      and in the respective cancer tissue donor. The other five CPECs and related
      cancer tissue donors and all normal and cancer PFCs expressed ERalpha messenger
      ribonucleic acid alone. Immunoblot analysis, using a polyclonal anti-ERbeta (C
      terminal) antibody, demonstrated ERbeta protein in all NPEC lysates and in one of
      the six CPECS: ERalpha protein was expressed in both NPECs and CPECs when a
      polyclonal antibody directed against the ERalpha N-terminal domain was used. In
      contrast, ERalpha protein was not detected in two of the six CPEC lysates when
      ERalpha C-terminal monoclonal antibodies were used. Using a set of primers
      designed to amplify the region from exons 6-8, RT-PCR analysis demonstrated the
      absence of the expected transcript in these cells. The present study shows that
      the ERbeta gene is expressed together with ERalpha in normal prostates and NPECs,
      whereas it is barely detectable in prostate cancer and CPECS: Moreover, in some
      CPECs, the ERalpha gene may be transcribed in a changed protein, resulting from
      the expression of a deletion variant. Together, these data suggest that prostate
      malignancy is associated with a potential disorder of ER-mediated pathways.

PMID- 11344206
TI  - Evidence for genetic heterogeneity of pseudohypoaldosteronism type 1:
      identification of a novel mutation in the human mineralocorticoid receptor in one
      sporadic case and no mutations in two autosomal dominant kindreds.
AB  - Pseudohypoaldosteronism type 1 (PHA1) is characterized by neonatal salt wasting
      resistant to mineralocorticoids. There are 2 forms of PHA1: the autosomal
      recessive form with symptoms persisting into adulthood, caused by mutations in
      the amiloride-sensitive luminal sodium channel, and the autosomal dominant or
      sporadic form, which shows milder symptoms that remit with age. Mutations in the
      gene encoding the human mineralocorticoid receptor (hMR) are, at least in some
      patients, responsible for the latter form of PHA1. We here report the results of
      a genetic study in a sporadic case and in 5 affected patients from 2 families
      with autosomal dominant PHA1. In the sporadic case we identified a new frameshift
      mutation, Ins2871C, in exon 9 of the hMR gene. Family members were asymptomatic
      and had no mutation. This mutation is the first described in exon 9 and impairs
      the last 27 amino acids of the hormone-binding domain. In 2 kindreds with
      autosomal dominant PHA1 we found no mutation of the hMR gene. Our results confirm
      the hypothesis that autosomal dominant or sporadic PHA1 is a genetically
      heterogeneous disease involving other, as yet unidentified, genes.

PMID- 11344207
TI  - Insulin-like growth factor (IGF)-II inhibition of endometrial stromal cell tissue
      inhibitor of metalloproteinase-3 and IGF-binding protein-1 suggests paracrine
      interactions at the decidua:trophoblast interface during human implantation.
AB  - In human pregnancy, insulin-like growth factor (IGF)-II messenger RNA (mRNA) is
      expressed at the maternal-fetal interface exclusively by the placental
      trophoblast. Highest levels are expressed by the invading extravillous
      trophoblasts, which also secrete matrix metalloproteinases as they degrade the
      decidual extracellular matrix. In contrast, the maternal decidua expresses high
      levels of IGF-binding protein (IGFBP)-1 and tissue inhibitors of matrix
      metalloproteinase (TIMPs), both of which inhibit trophoblast invasiveness in
      vitro. The present study investigated the hypothesis that IGF-II may serve as a
      paracrine modulator of maternal restraints on invasion, by examining its effects
      on TIMP-3 and IGFBP-1 expression by decidualized endometrial stromal cells. Human
      endometrial stromal cells were decidualized in vitro with progesterone (P), after
      which 0-130 nM IGF-II and IGF analogs were added. IGFBP-1 in conditioned medium
      was assayed by immunoradiometric assay. In addition, Northern analyses were
      conducted using a PCR-generated 421-bp complementary DNA (cDNA) fragment
      corresponding to nucleotides 132-553 of the human TIMP-3 cDNA, and a 934-bp EcoRI
      fragment of the human IGFBP-1 cDNA. TIMP-3 mRNA transcripts of 2.2, 2.5, and 4.4
      kilobases were detected in decidualized stromal cells not treated with IGF-II,
      but not detected in nondecidualized stromal cells, consistent with its known
      induction upon decidualization and in response to P. In decidualized stromal
      cells, IGF-II and Des(1-6) IGF-II, an analog with reduced affinity for IGFBPs,
      caused a dose-dependent inhibition of TIMP-3 mRNA expression. Long R(3) IGF-I, an
      IGF analog with minimal affinity for IGFBPs, also significantly inhibited (79 +/-
      0.3%) TIMP-3 mRNA expression in these cells at 6 nM. Decidualized stromal cells
      secreted IGFBP-1 and expressed a 1.5-kilobase IGFBP-1 transcript, which was not
      detected in nondecidualized cells, consistent with its known induction upon
      decidualization and in response to P. IGF-II caused a dose-dependent inhibition
      of IGFBP-1 mRNA expression and protein secretion in decidualized stromal cells
      when added in molar excess of endogenous IGFBP-1 levels, with virtually complete
      inhibition at higher concentrations of IGF-II (65 and 130 nM). By comparison,
      Long R(3) IGF-I inhibited IGFBP-1 expression with a 50% effective dose of 0.2-0.4
      nM. These data suggest that the invading trophoblast has the capacity, via IGF
      II, to inhibit maternal restraints on trophoblast invasiveness by regulating
      decidual TIMP-3 and IGFBP-1.

PMID- 11344208
TI  - Interactions of leptin and thyrotropin 24-hour secretory profiles in short normal
      children.
AB  - Thyroid hormones and leptin have effects on similar aspects of body homeostasis,
      such as energy expenditure, thermogenesis, and metabolic efficiency. Thus, the
      cross-talk between the thyrostat and the lipostat might play a crucial role in
      the maintenance of body homeostasis. To investigate the relationship between the
      hypothalamic-pituitary-thyroid (HPT) axis and leptin under physiological
      conditions, we evaluated the pulsatility and circadian rhythmicity and time-cross
      correlated the 24-h secretory patterns of leptin and TSH in 12 short normal
      prepubertal children (6 girls and 6 boys). In both male and female subjects,
      leptin was secreted in a pulsatile and circadian fashion, with a nocturnal leptin
      surge that was more pronounced in males than in females. Mean 24-h leptin levels
      and total area under the curve were significantly higher in girls than in boys.
      This was mainly due to the nighttime mean leptin levels and total area under the
      curve, which were higher than those in boys. The cross-correlated 24-h leptin and
      TSH levels revealed significant positive and negative correlations. The positive
      one, of leptin over TSH, suggests a positive feedback regulation by leptin on the
      HPT axis, which might play an important role in triggering the neuroendocrine
      response to starvation, including decreased thyroid hormone levels. The negative
      correlation, of TSH over leptin, could explain the compensatory changes in
      adipocyte metabolism, and indirectly in circulating leptin levels, in response to
      alterations in thyroid status. In conclusion, we suggest that under baseline
      physiological conditions, the HPT axis has a prevailing inhibitory effect on
      leptin secretion, whereas leptin has a prevailing positive effect on the HPT
      axis. The sexual dimorphism in leptin levels does not seem to influence in a
      major way the interactions between the HPT axis and leptin.

PMID- 11344209
TI  - Intracellular partition of plasma glucose disposal in hypertensive and
      normotensive subjects with type 2 diabetes mellitus.
AB  - The aim of this study was to ascertain whether the presence of hypertension
      conveys a more severe degree of insulin resistance in type 2 diabetes mellitus
      and, if so, which biochemical pathways are involved. We quantitated the rates of
      total glucose disposal, glycogen synthesis (GS), glycolysis, glucose oxidation,
      endogenous glucose production, and LOX in the basal state and during a 4-h
      euglycemic ( approximately 5 mM) hyperinsulinemic ( approximately 300 pM) clamp
      carried out in combination with a dual-tracer infusion ([(3)H]-3- and [(14)C]-U-D
      glucose) and indirect calorimetry in 42 nonobese noninsulin-treated type 2
      diabetic subjects (22 hypertensive and 20 normotensive) and 23 nonobese
      nondiabetic subjects (9 without and 14 with essential hypertension). Compared
      with normotensive controls, both groups of diabetic subjects were markedly
      insulin resistant. In the basal state, all glucose fluxes were similar in
      diabetic subjects with or without hypertension. During insulin infusion, total
      glucose disposal was significantly reduced in hypertensive diabetic subjects,
      compared with their normotensive counterparts (18.7 +/- 1.0 vs. 28.6 +/- 3.0
      micromol/min.kg lean body mass; P < 0.01). This difference was almost entirely
      explained by a marked reduction in GS (4.5 +/- 2.0 vs. 12.5 +/- 3.3
      micromol/min.kg lean body mass; P < 0.01). Endogenous glucose production was not
      different in the two diabetic groups during insulin infusion and was
      significantly higher than in normotensive controls. Lipid oxidation was less
      suppressed by hyperinsulinemia in hypertensive than in normotensive diabetic
      subjects (1.46 +/- 0.1 vs. 0.91 +/- 0.1 micromol/min.kg lean body mass; P <
      0.01). Glucose fluxes were not significantly different in nondiabetic subjects
      with essential hypertension and in normotensive diabetic individuals. These
      results indicate that hypertension markedly aggravates insulin resistance
      featuring type 2 diabetes mellitus. The molecular defects underlying this
      phenomenon involve primarily GS.

PMID- 11344210
TI  - Increased expression of thyroid hormone receptor isoforms in end-stage human
      congestive heart failure.
AB  - Thyroid hormone plays an important role on myocardial development and function.
      The local effects of thyroid hormone are mediated by the receptor isoforms
      ultimately driving the expression of cardiac-specific genes. Although overt and
      subclinical thyroid dysfunction causes well-known changes in the cardiovascular
      system, little is known about local thyroid hormone action in normal and failing
      human myocardium. With a newly developed multiplex competitive RT-PCR method, we
      evaluated the expression of thyroid hormone receptor (TR) isoforms alpha-1, alpha
      2, and beta-1 in normal human hearts and in end-stage congestive heart failure. A
      statistically significant difference in the expression of all three TR isoforms
      was observed among samples from normal subjects, ischemic heart disease (IHD),
      and dilated cardiomyopathy (DCM). In DCM, compared with normal, the studied TR
      isoforms were significantly increased. In IHD, the increased expression was found
      significant only for alpha-1 and alpha-2 isoforms. No differences were observed
      between the pathologic groups. In conclusion, a coordinated increment in the
      expression of the TR isoforms was observed in both DCM and IHD by multiplex
      competitive RT-PCR. The observed changes could represent a compensatory mechanism
      to myocardial failure or to locally altered thyroid hormone action.

PMID- 11344211
TI  - Physiological levels of glucagon do not influence lipolysis in abdominal adipose
      tissue as assessed by microdialysis.
AB  - To determine whether glucagon stimulates lipolysis in adipose tissue, seven
      healthy young male volunteers were studied, with indwelling microdialysis
      catheters placed sc in abdominal adipose tissue. Subjects were studied three
      times: 1) during euglucagonemia (EG; glucagon infusion rate, 0.5 ng/kg.min); 2)
      during hyperglucagonemia (HG; (glucagon infusion rate, 1.5 ng/kg.min); and 3)
      during EG and a concomitant glucose infusion mimicking the glucose profile from
      the day of HG (EG+G). Somatostatin (450 microg/h) was infused to suppress
      hormonal secretion, and replacement doses of insulin and GH were administered.
      Sampling was done every 30 min for 420 min. Baseline circulating values of
      insulin, C-peptide, glucagon, GH, glycerol, and free fatty acids were comparable
      in all three conditions. During EG and EG+G, plasma glucagon was maintained at
      fasting level (20-40 ng/L); whereas, during HG, it increased (110-130 ng/L).
      Interstitial concentrations of glycerol were similar in the three conditions
      [30,870 +/- 5,946 (EG) vs. 31,074 +/- 7,092 (HG) vs. 29,451 +/- 6,217 (EG+G)
      micromol/L.120 min, P = 0.98]. Plasma glycerol (ANOVA, P = 0.5) and free fatty
      acids (ANOVA, P = 0.3) were comparable during the different glucagon challenges.
      We conclude that HG per se does not increase interstitial glycerol (and thus
      lipolysis) in abdominal sc adipose tissue; nor does modest hyperglycemia, during
      basal insulinemia and glucagonemia, influence indices of abdominal sc lipolysis.

PMID- 11344212
TI  - Identification of extracellular matrix components and their integrin receptors in
      the human fetal adrenal gland.
AB  - The development of the human fetal adrenal gland is characterized by a gradient
      of mitotic activity, cell migration, and cell apoptosis, all of which dictate its
      particular function. Such plasticity may possibly be under the control of the
      extracellular environment. The goal of this study was to identify components of
      the extracellular matrix in second-trimester fetal adrenal glands. Whereas
      collagen IV was expressed evenly throughout the gland, both fibronectin and
      laminin demonstrated a mirror-imaged distribution, with higher expression of
      fibronectin in the central portion and laminin at the periphery of the gland. The
      integrin subunit alpha1 was found mainly in the definitive zone and the alpha2
      subunit mainly in the transitional zone, whereas integrin alpha3 (which binds
      both fibronectin and laminin) was detected only in the fetal zone. The beta2
      subunit was observed solely in chromaffin cells. Such specific gradients of
      integrin and MEC component expression suggest that the extracellular environment
      does play a definite role during adrenal gland development. Indeed, compared with
      that in untreated plastic dishes, ACTH stimulation of dehydroepiandrosterone
      sulfate and cortisol was enhanced by collagen IV. In addition, fibronectin
      enhanced dehydroepiandrosterone sulfate but decreased cortisol secretion,
      compared with collagen IV substrates. These results provide fundamental insight
      into the contribution of the microenvironment in cellular processes leading to
      fetal adrenal gland development.

PMID- 11344213
TI  - Short-term glucosamine infusion does not affect insulin sensitivity in humans.
AB  - Overactivity of the hexosamine biosynthetic pathway may underlie hyperglycemia
      associated insulin resistance, but to date human studies are lacking. Hexosamine
      pathway activation can be mimicked by glucosamine (GlcN). In the present placebo
      controlled study we determined whether GlcN infusion affects insulin resistance
      in vivo. In 18 healthy subjects, we applied the double forearm balance technique
      (infused arm vs. control arm) combined with the euglycemic hyperinsulinemic clamp
      (60 mU/m(2).min insulin) for at least 300 min. During the clamp, subjects
      received infusions in the brachial artery of 4 micromol/dL.min GlcN from 90-240
      min (n = 6) or from 0-300 min (n = 6) or saline (placebo; n = 6). We studied the
      effects of GlcN on forearm glucose uptake (FGU; infused arm vs. control arm, and
      vs. placebo experiments) and on whole body glucose uptake. GlcN infusion raised
      the plasma GlcN concentration in the infusion arms to 0.42 +/- 0.14 and 0.81 +/-
      0.46 mmol/L; plasma GlcN remained very low (< 0.07 mmol/L) in the control arms
      and in the placebo group. GlcN infusion did not change forearm blood flow. During
      insulin, FGU increased more than 10-fold. At all time points, FGU was similar in
      the GlcN-infused arm compared with the control arm and was not different from FGU
      in the placebo experiments. Similar results were obtained for forearm
      arteriovenous glucose differences or extraction and for whole body glucose
      uptake. Thus, despite relevant GlcN concentrations for 5 h in the infused
      forearm, GlcN had no effect on insulin-induced glucose uptake. These results do
      not support involvement of the hexosamine pathway in the regulation of insulin
      sensitivity in humans, at least not in the short-term setting.

PMID- 11344214
TI  - Insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) binds to fibronectin
      (FN): demonstration of IGF-I/IGFBP-3/fn ternary complexes in human plasma.
AB  - We used a yeast two-hybrid system to identify binding partners for insulin-like
      growth factor (IGF)-binding protein-3 (IGFBP-3). A partial complementary DNA
      encoding the carboxyl-terminal of fibronectin (FN), including the cell binding
      site, the heparin-binding domain, and the fibrin-binding domain, was identified
      in a screen of a human placental complementary DNA library. The interaction of
      IGFBP-3 with FN and the 40-kDa heparin-binding carboxyl-terminal fragment of FN
      was confirmed using Western ligand blotting. Both glycosylated and
      nonglycosylated IGFBP-3 bound to FN with a K(d) of approximately 0.3 nmol/L. IGF
      I and IGFBP-1 had no effect on IGFBP-3 binding to FN. Competitive inhibition of
      IGFBP-3 binding to FN was observed in the presence of IGFBP-5 and heparin. The
      binding affinity of the immobilized IGFBP-3/FN complex for [(125)I]IGF-I (K(d) =
      0.8 nmol/L) was similar to that of IGFBP-3 alone. The presence of IGF-I/IGFBP
      3/FN ternary complexes in human plasma was demonstrated by coimmunoprecipitation
      of IGFBP-3 and [(125)I]IGF-I with anti-FN monoclonal antibody. These data
      indicate that FN may have a role in the transportation of IGFBP-3 and IGF-I in
      the circulation and the sequestration of these proteins in tissues.

PMID- 11344215
TI  - Expression of cyclic adenosine 3',5'-monophosphate (cAMP)-responsive element
      binding protein and inducible-cAMP early repressor genes in growth hormone
      secreting pituitary adenomas with or without mutations of the Gsalpha gene.
AB  - In about 30-40% of GH-secreting adenomas, gain-of-function mutations of the
      Gsalpha gene, which convert this gene into an oncogene termed gsp, occur. Gsalpha
      mutations have been related to pituitary tumorigenesis. We focused on 2 nuclear
      transcription factors that are final targets of the cAMP-dependent pathway and
      are positively regulated by cAMP signaling, i.e. the cAMP-responsive element
      binding protein (CREB) and the inducible cAMP early repressor (ICER), that
      derives from alternative splicing of cAMP-responsive element modulator gene. We
      examined 21 GH-secreting adenomas, 8 with (gsp(+)) and 13 without (gsp(-)) a
      mutated Gsalpha. Analysis of CREB and ICER I/II messenger RNA revealed that the
      levels of both transcripts were higher in gsp(+) than in gsp(-) tumors
      (CREB/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mean optical density +/-
      SE, 2.34 +/- 0.36 in gsp(+) vs. 0.99 +/- 0.22 in gsp(-), P = 0.003; ICER I/GAPDH,
      0.53 +/- 0.15 in gsp(+) vs. 0.14 +/- 0.07 in gsp(-), P = 0.01; ICER II/GAPDH, 1.5
      +/- 0.21 in gsp(+) vs. 0.83 +/- 0.13 in gsp(-), P = 0.01), although a few cases
      in both groups did not display this pattern of expression. Moreover, no positive
      correlation between the levels of CREB and ICER transcripts was observed,
      suggesting the possible presence of alterations in the mechanisms by which cAMP
      signaling directs the expression of CREB and/or ICER genes. Our results indicate
      a complex pattern of expression of nuclear transcription factors that mediate
      cAMP action in both gsp(+) and gsp(-) tumors, suggesting that, beside Gsalpha
      gene mutations, different and partially unknown molecular events may contribute
      to the pathogenesis of these tumors.

PMID- 11344216
TI  - Norepinephrine infusion during moderate-intensity exercise increases glucose
      production and uptake.
AB  - A role for the increase in circulating norepinephrine (NE) during intense
      exercise [IE; > or = 80% maximum O(2) uptake (VO(2max))] in the marked increment
      in glucose rate of production (Ra) during IE is hypothesized. Seven fit male
      subjects (27 +/- 2 yr old; body mass index, 23 +/- 1 kg/m(2); VO(2max), 63 +/- 5
      mL/kg.min) underwent 40 min of postabsorptive moderate-intensity (53% VO(2max))
      cycle ergometer exercise (126 +/- 14 W), once without [control (CON)] and once
      with NE infusion (0.1 microg/kg.min) from 30-40 min (NE). With infusion, plasma
      NE reached 15.9 +/- 1.0 nM (8-fold rest, 2-fold CON). Ra doubled to 4.40 +/- 0.44
      in CON, but rose to 7.55 +/- 0.68 mg/kg.min with NE infusion (P = 0.003). Ra
      correlated strongly (r(2) = 0.92, P < 0.02) with plasma NE during and immediately
      after infusion. With NE infusion, peak glucose uptake [rate of disappearance
      (Rd), 6.57 +/- 0.59 vs. 4.53 +/- 0.55 mg/kg.min, P < 0.02] and glucose metabolic
      clearance rate (P < 0.05) were higher than in CON. Glycemia rose minimally during
      the NE infusion but did not differ between groups at any time during exercise.
      Glucagon-to-insulin ratio increased minimally, and epinephrine increased
      approximately 2.5- to 3-fold at peak but did not differ between groups. Thus, NE
      infusion during moderate exercise led to increments in Ra and Rd in fit
      individuals, supporting a possible contributory role for the increase of plasma
      NE in IE. NE effects on Rd and metabolic clearance rate during exercise may
      differ from its effects at rest.

PMID- 11344217
TI  - The regulation of apoptosis by activin and transforming growth factor-beta in
      early neoplastic and tumorigenic ovarian surface epithelium.
AB  - Most ovarian neoplasms arise from the ovarian surface epithelium (OSE), and
      multiple growth factors have been implicated to influence the transformation from
      OSE. The present study was performed to investigate the role of activin and
      transforming growth factor-beta (TGFbeta) in normal and neoplastic OSE cells. An
      immortalized OSE cell line (IOSE-29) was generated from normal OSE by
      transfecting simian virus 40 large T antigen and was rendered tumorigenic after
      subsequent transfection with the E-cadherin gene (IOSE-29EC). The activin/inhibin
      subunits and activin receptors were expressed at both messenger ribonucleic acids
      and protein levels in these cells, suggesting that activin may have an autocrine
      role in neoplastic OSE cells. Treatments with activin (1-100 ng/mL) resulted in a
      significant decrease in cell proliferation in both IOSE-29 and IOSE-29EC cells,
      although we have shown that it stimulated the growth of ovarian cancer cells and
      had no effect on normal OSE. This inhibitory effect was attenuated with
      cotreatment with follistatin. Treatment with TGFbeta (0.1-10 ng/mL) also
      significantly decreased the proliferation of normal, IOSE-29, and IOSE-29EC cells
      in a dose-dependent manner. In addition, treatments with both activin and TGFbeta
      resulted in an increase in DNA fragmentation in IOSE-29EC cells in a dose
      dependent manner. This apoptotic effect of activin was attenuated by cotreatment
      with follistatin. Treatment with TGFbeta (1 and 10 ng/mL) resulted in a
      significant decrease in Bcl-2 protein (up to 50%) in IOSE-29EC, whereas no
      difference was observed in Bax protein levels. Therefore, down-regulated Bcl-2 by
      TGFbeta may eventually induce apoptosis in IOSE-29EC cells. In contrast, no
      difference was observed in Bax and Bcl-2 protein expression after treatment with
      activin. In conclusion, the present study indicates that activin and TGFbeta
      inhibited growth and induced apoptosis in early neoplastic (IOSE-29) and
      tumorigenic OSE (IOSE-29EC) cells. Furthermore, antiapoptotic Bcl-2 protein was
      down-regulated by TGFbeta, whereas no difference was produced in Bax protein by
      activin or TGFbeta treatment or in Bcl-2 protein by activin. These results
      suggest that activin and TGFbeta may play a role in growth inhibition and
      induction of apoptosis in early neoplastic and tumorigenic stage of ovarian
      cancer.

PMID- 11344218
TI  - Branched chain amino acids activate messenger ribonucleic acid translation
      regulatory proteins in human skeletal muscle, and glucocorticoids blunt this
      action.
AB  - Branched chain amino acids (BCAA) are particularly effective anabolic agents.
      Recent in vitro studies suggest that amino acids, particularly leucine, activate
      a signaling pathway that enhances messenger ribonucleic acid translation and
      protein synthesis. The physiological relevance of these findings to normal human
      physiology is uncertain. We examined the effects of BCAA on the phosphorylation
      of eukaryotic initiation factor 4E-binding protein 1 (eIF4E-BP1) and ribosomal
      protein S6 kinase (p70(S6K)) in skeletal muscle of seven healthy volunteers. We
      simultaneously examined whether BCAA affect urinary nitrogen excretion and
      forearm skeletal muscle protein turnover and whether the catabolic action of
      glucocorticoids could be mediated in part by inhibition of the action of BCAA on
      the protein synthetic apparatus. BCAA infusion decreased urinary nitrogen
      excretion (P < 0.02), whole body phenylalanine flux (P < 0.02), plasma
      phenylalanine concentration (P < 0.001), and improved forearm phenylalanine
      balance (P = 0.03). BCAA also increased the phosphorylation of both eIF4E-BP1 (P
      < 0.02) and p70(S6K) (P < 0.03), consistent with an action to activate the
      protein synthetic apparatus. Dexamethasone increased plasma phenylalanine
      concentration (P < 0.001), prevented the BCAA-induced anabolic shift in forearm
      protein balance, and inhibited their action on the phosphorylation of p70(S6K).
      We conclude that in human skeletal muscle BCAA act directly as nutrient signals
      to activate messenger ribonucleic acid translation and potentiate protein
      synthesis. Glucocorticoids interfere with this action, and that may be part of
      the mechanism by which they promote net protein catabolism in muscle.

PMID- 11344219
TI  - Antagonists of growth hormone-releasing hormone and somatostatin analog RC-160
      inhibit the growth of the OV-1063 human epithelial ovarian cancer cell line
      xenografted into nude mice.
AB  - The effects of antagonists of GHRH and the somatostatin analog RC-160 on the
      growth of OV-1063 human epithelial ovarian cancer cells xenografted into nude
      mice were investigated. Treatment with 20 microg/day of the GHRH antagonist JV-1
      36 or MZ-5-156 and 60 microg/day of the somatostatin analog RC-160 for 25 days
      decreased tumor volume by 70.9% (P < 0.01), 58.3% (P < 0.05), and 60.6% (P <
      0.01), respectively, vs. the control value. The levels of GH in serum were
      decreased in all of the treated groups, but only RC-160 significantly reduced
      serum insulin-like growth factor I (IGF-I). The levels of messenger ribonucleic
      acid (mRNA) for IGF-I and -II and for their receptors in OV-1063 tumors were
      investigated by multiplex RT-PCR. No expression of mRNA for IGF-I was detected,
      but treatment with JV-1-136 caused a 51.8% decrease (P < 0.05) in the level of
      mRNA for IGF-II in tumors. Exposure of OV-1063 cells cultured in vitro to GHRH,
      IGF-I, or IGF-II significantly (P < 0.05) stimulated cell growth, but 10(-5)
      mol/L JV-1-36 nearly completely inhibited (P < 0.001) OV-1063 cell proliferation.
      OV-1063 tumors expressed mRNA for GHRH receptors and showed the presence of
      binding sites for GHRH. Our results indicate that antagonistic analogs of GHRH
      and the somatostatin analog RC-160 inhibit the growth of epithelial ovarian
      cancers. The effects of RC-160 seem to be exerted more on the pituitary GH
      hepatic IGF-I axis, whereas GHRH antagonists appear to reduce IGF-II production
      and interfere with the autocrine regulatory pathway. The antitumorigenic action
      of GHRH antagonists appears to be mediated by GHRH receptors found in OV-1063
      tumors.

PMID- 11344220
TI  - Free fatty acids inhibit the glucose-stimulated increase of intramuscular glucose
      6-phosphate concentration in humans.
AB  - To test Randle's hypothesis we examined whether free fatty acids (FFAs) affect
      glucose-stimulated glucose transport/phosphorylation and allosteric mediators of
      muscle glucose metabolism under conditions of fasting peripheral insulinemia.
      Seven healthy men were studied during somatostatin-glucose-insulin clamp tests
      [plasma insulin, 50 pmol/L; plasma glucose, 5 mmol/L (0-180 min), 10 mmol/L (180
      300 min)] in the presence of low (0.05 mmol/L) and increased (2.6 mmol/L) plasma
      FFA concentrations. (31)P and (1)H nuclear magnetic resonance spectroscopy was
      used to determine intracellular concentrations of glucose-6-phosphate (G6P),
      inorganic phosphate, phosphocreatine, ADP, pH, and intramyocellular lipids. Rates
      of glucose turnover were measured using D-[6,6-(2)H(2)]glucose. Plasma FFA
      elevation reduced rates of glucose uptake at the end of the euglycemic period
      (R(d 150-180 min): 8.6 +/- 0.5 vs. 12.6 +/- 1.6 micromol/kg.min, P < 0.05) and
      during hyperglycemia (R(d 270-300 min): 9.9 +/- 0.6 vs. 22.3 +/- 1.7
      micromol/kg.min, P < 0.01). Similarly, intramuscular G6P was lower at the end of
      both euglycemic (G6P(167-180 min): -22 +/- 7 vs. +24 +/- 7 micromol/L, P < 0.05)
      and hyperglycemic periods (G6P(287-300 min): -7 +/- 9 vs. +28 +/- 7 micromol/L, P
      < 0.05). Changes in intracellular inorganic phosphate exhibited a similar
      pattern, whereas FFA did not affect phosphocreatine, ADP, pH, and
      intramyocellular lipid contents. In conclusion, the lack of an increase in
      muscular G6P along with reduction of whole body glucose clearance indicates that
      FFA might directly inhibit glucose transport/phosphorylation in skeletal muscle.

PMID- 11344221
TI  - Somatostatin receptor subtypes 2 and 5 differentially affect proliferation in
      vitro of the human medullary thyroid carcinoma cell line tt.
AB  - Somatostatin and its receptors (SSTR1 to SSTR5) are expressed in normal human
      parafollicular C cells and medullary thyroid carcinoma (MTC), but the role of
      SSTR subtypes in cell growth regulation is still not clear. The present study
      demonstrates that the human MTC cell line TT stably expresses all the SSTR
      subtypes and responds to SSTR2 and SSTR5 activation by subtype-selective agonists
      with two different patterns in terms of [(3)H]thymidine ([(3)H]thy) incorporation
      and cell number. The SSTR2 preferential agonists (BIM-23120, BIM-23197, BIM
      23190, and BIM-23014; 10(-9)-10(-6) M), significantly suppressed [(3)H]thy
      incorporation (58-13%) and reduced cell proliferation (50-28%), whereas the SSTR5
      selective agonist, BIM-23206 (10(-9)-10(-6) M), significantly increased [(3)H]thy
      incorporation in TT cells (80-175%), but failed to influence cell proliferation.
      SSTR2 antagonist (BIM-23627) counteracted the action of SSTR2 preferential
      agonists on TT cells. Furthermore, increasing concentrations of SSTR5-selective
      agonists, BIM-23206, dose-dependently prevented the suppression of TT cell
      [(3)H]thy incorporation and proliferation produced by SSTR2 preferential agonist,
      BIM-23120, showing an antagonism between these compounds. The following
      conclusions were reached: 1) the human MTC cell line TT expresses all SSTR
      subtypes; 2) SSTR2 activation inhibits DNA synthesis and cell proliferation,
      whereas SSTR5 activation increases DNA synthesis; and 3) SSTR2 preferential
      agonist (BIM-23120) can antagonise SSTR5-selective agonist (BIM-23206) action and
      vice versa. These findings suggest a tissue-specific function and a tissue
      specific interaction between the two receptors.

PMID- 11344222
TI  - Ligands for peroxisome proliferator-activated receptor gamma inhibit growth and
      induce apoptosis of human papillary thyroid carcinoma cells.
AB  - Ligands for peroxisome proliferator-activated receptor gamma (PPARgamma) induce
      apoptosis and exert antiproliferative effects on several carcinoma cell lines.
      The present study investigates the expression of PPARgamma and the possibility
      that agonists for PPARgamma also inhibit the growth of human thyroid carcinoma
      cells. We examined this hypothesis using six cell lines, designated BHP thyroid
      carcinoma cells, which originated from patients with papillary thyroid carcinoma.
      RT-PCR analysis revealed that the thyroid carcinoma cell lines BHP2-7, 7-13, 10
      3, and 18-21 express PPARgamma. More PPARgamma was expressed in carcinoma than in
      adjacent normal thyroid tissue in three of six samples of human papillary
      carcinoma of the thyroid. PPARgamma-positive thyroid carcinoma cells were treated
      with agonists of PPARgamma, troglitazone, BRL 49653, and 15-deoxy-12,14
      prostaglandin J2. Troglitazone (10 micromol/L), BRL 49653 (10 micromol/L), and 15
      deoxy-12,14-prostaglandin J2 (1 microg/mL) decreased [(3)H]thymidine
      incorporation and reduced cell number, respectively, in BHP carcinoma cell lines
      that expressed PPARgamma. Under low serum conditions, ligands for PPARgamma
      induced condensation of the nucleus and fragmentation of chromatin into
      nucleosome ladders. These findings indicate that the death of thyroid carcinoma
      cells is a form of apoptosis. To investigate the molecular mechanism of the
      apoptosis, we assessed expression of the apoptosis-regulatory genes bcl-2, bax,
      and c-myc. Troglitazone significantly increased the expression of c-myc messenger
      RNA but had no effect on the expression of bcl-2 and bax in thyroid carcinoma
      cells. These results suggest that, at least in part, the induction of apoptosis
      in human papillary thyroid carcinoma cells may be due to an increase of c-myc.
      Troglitazone (500 mg/kg.day) significantly inhibited tumor growth and prevented
      distant metastasis of BHP18-21 tumors in nude mice in vivo. Taken together, these
      results suggest that PPARgamma agonist inhibit cell growth of some types of human
      thyroid cancer.

PMID- 11344223
TI  - G-308A polymorphism of the tumor necrosis factor alpha gene promoter and salivary
      cortisol secretion.
AB  - The objective of the current study was to examine the potential impact of the G-
      >A substitution at position -308 of the tumor necrosis factor alpha (TNF-alpha)
      gene promoter on obesity and estimates of insulin, glucose, and lipid metabolism
      as well as circulating hormones including salivary cortisol in 284 unrelated
      Swedish men born in 1944. The subjects were genotyped by using PCR amplification
      of the 5' untranslated region of the TNF-alpha gene followed by digestion with
      the restriction enzyme NcoI. The frequencies were 0.77 for allele G and 0.23 for
      allele A. Tests for differences in salivary cortisol levels between the TNF-alpha
      genotypes revealed that there were significantly higher cortisol levels in the
      morning, before as well as 30 and 60 min after stimulation by a standardized
      lunch in homozygotes for the rare allele in comparison with the other genotypes.
      In addition, homozygotes for the rare allele had a tendency toward higher mean
      values of body mass index, waist to hip ratio, and abdominal sagittal diameter
      compared with the other genotype groups. The results also indicated a weak trend
      toward elevated insulin and glucose levels among men with the A/A genotype. In
      conclusion, a G-->A polymorphism in the 5' untranslated region of the TNF-alpha
      gene is associated with elevated morning cortisol levels as well as elevated
      postprandial cortisol secretion. This increase in cortisol secretion might be the
      endocrine mechanism underlying the previously observed associations between the
      NcoI TNF-alpha polymorphism and obesity as well as insulin resistance. However,
      to what extent this polymorphism is associated with these conditions is uncertain
      from the present data.

PMID- 11344224
TI  - Studies of genetic variability of the glucose transporter 2 promoter in patients
      with type 2 diabetes mellitus.
AB  - This study was performed to test the hypothesis that genetic variation in the
      promoter of the glucose transporter 2 (GLUT2) might predispose to prediabetic
      phenotypes or type 2 diabetes. A total of 1611 bp comprising the minimal promoter
      region of the GLUT2 gene were examined by combined single-strand conformational
      polymorphism and heteroduplex analysis followed by direct sequencing of
      identified variants on genomic DNA from 96 randomly recruited Danish type 2
      diabetic patients. We identified 4 nucleotide variants, -447g-->a, -149c-->a, 
      122t-->c, and -44g-->a. None of the variants were positioned in known or presumed
      transcription factor binding sites, TATA-box, or transcriptional start site.
      Association studies of the -149c-->a, -122t-->c, and -44g-->a variants revealed
      that the variants were as prevalent in 320 type 2 diabetic patients [11.0% (95%
      confidence interval, 8.4-13.6), 9.8% (7.4-12.2), and 29.0% (24.4-33.6),
      respectively] as in 241 age-matched glucose-tolerant subjects [13.1% (9.8-16.4),
      11.2% (8.3-14.1), and 33.4% (28.8-38.0), respectively]. The -447g-->a mutation
      was only identified in a single diabetic patient and did not show cosegregation
      with diabetes in the family of the proband. The three common variants showed in a
      primary genotype-phenotype study comprising 241 glucose-tolerant middle-aged
      subjects association to increased plasma glucose levels during an oral glucose
      tolerance test. However, this result could not be replicated in a second sample
      of 298 60-yr-old glucose-tolerant subjects. In conclusion, we found no evidence
      supporting the hypothesis that genetic variability in the minimal promoter of the
      GLUT2 is associated with type 2 diabetes or prediabetic phenotypes in the Danish
      population.

PMID- 11344225
TI  - Analysis of ret/PTC gene rearrangements refines the fine needle aspiration
      diagnosis of thyroid cancer.
AB  - Papillary carcinoma (PC) represents the most common malignancy of the thyroid
      gland. Therefore, the assessment of fine needle aspiration biopsies of thyroid
      nodules rests heavily on the identification of nuclear features of PC. The
      ret/PTC oncogene, formed by several gene rearrangements, is specific for PC among
      thyroid tumors. In this study we examined thyroid aspirates for the presence of
      ret/PTC gene rearrangements by RT-PCR and Southern hybridization. We
      prospectively collected thyroid aspirates in Cytolyt solution and prepared slides
      for cytological examination using the ThinPrep method. All remaining material was
      then used for nucleic acid extraction with subsequent RT-PCR for the housekeeping
      gene PGK-1 to ensure ribonucleic acid integrity, for thyroglobulin to ensure the
      presence of follicular epithelial cells, and for the three most common ret/PTC
      gene rearrangements (ret/PTC-1, -2, and -3). The results of the first 73 cases
      with surgical follow-up were correlated with the cytological diagnosis and final
      histopathology. ret/PTC gene rearrangements were detected in 17 of 33 samples
      (52%) that were PC on histopathology; the presence of gene rearrangements was
      confirmed by molecular analysis of corresponding surgically resected frozen
      tissue. There were no false positives. The identification of ret/PTC gene
      rearrangements refined the diagnosis of PC in 9 of 15 specimens (60%) that would
      otherwise have been considered indeterminate and in 2 of 6 that were considered
      insufficient for cytological diagnosis. The results indicate that RT-PCR for
      ret/PTC is a specific marker that can be applied to fine needle aspiration
      biopsies and improves the diagnosis of malignancy when used as an adjunct to
      traditional cytology.

PMID- 11344226
TI  - beta(1)- and beta(2)-Adrenoceptor-mediated thermogenesis and lipid utilization in
      obese and lean men.
AB  - The aim of this study was to elucidate the roles of the beta(1)- and the beta(2)
      adrenoceptors in thermogenesis and lipid utilization in obesity. The beta(1)
      adrenoceptor study was performed in 9 obese and 10 lean men and consisted of 4 30
      min periods during which subjects received consecutive infusions of 0, 3, 6, and
      9 microg/kg fat-free mass (FFM).min dobutamine. Energy expenditure, lipid
      oxidation, and plasma nonesterified fatty acids and glycerol concentrations
      increased similarly in both groups during beta(1)-adrenergic stimulation. The
      beta(2)-adrenoceptor study was performed in 10 obese and 11 lean men and involved
      3 45-min periods during which 0, 50, and 100 ng/kg FFM.min salbutamol were given
      in combination 1.2 microg/kg FFM.min atenolol (bolus, 50 microg/kg FFM). During
      beta(2)-adrenergic stimulation, the increases in energy expenditure and plasma
      nonesterified fatty acids and glycerol concentrations were reduced in the obese
      group. Furthermore, lipid oxidation significantly increased in the normal weight
      group, but remained similar in the overweight group. In conclusion, these data
      suggest that beta(1)-adrenoceptor-mediated metabolic processes are similar in
      both groups, but beta(2)-adrenoceptor-mediated increases in thermogenesis and
      lipid utilization are impaired in the obese.

PMID- 11344227
TI  - Angiotensin-I converting enzyme genotype-dependent benefit from hormone
      replacement therapy in isometric muscle strength and bone mineral density.
AB  - Low bone mineral density (BMD) and muscle weakness are major risk factors for
      postmenopausal osteoporotic fracture. Hormone replacement therapy (HRT) reverses
      the menopausal decline in maximum voluntary force of the adductor pollicis and
      reduces serum angiotensin-I converting enzyme (ACE) levels. The insertion (I)
      allele of the ACE gene polymorphism is associated with lower ACE activity and
      improved muscle efficiency in response to physical training. Therefore, we
      examined whether the presence of the I allele in postmenopausal women would
      affect the muscle response to HRT. Those taking HRT showed a significant gain in
      normalized muscle maximum voluntary force slope, the rate of which was strongly
      influenced by ACE genotype (16.0 +/- 1.53%, 14.3 +/- 2.67%, and 7.76 +/- 4.13%,
      mean +/- SEM for II, ID, and DD genotype, respectively; P = 0.017 for gene
      effect, P = 0.004 for I allele effect). There was also a significant ACE gene
      effect in the response of BMD to HRT in Ward's triangle (P = 0.03) and a
      significant I allele effect in the spine (P = 0.03), but not in the neck of femur
      or total hip. These data suggests that low ACE activity associated with the I
      allele confers an improved muscle and BMD response in postmenopausal women
      treated with HRT.

PMID- 11344228
TI  - Enhanced activity of the purine nucleotide cycle of the exercising muscle in
      patients with hyperthyroidism.
AB  - Myopathy frequently develops in patients with hyperthyroidism, but its precise
      mechanism is not clearly understood. In this study we focused on the purine
      nucleotide cycle, which contributes to ATP balance in skeletal muscles. To
      investigate purine metabolism in muscles, we measured metabolites related to the
      purine nucleotide cycle using the semiischemic forearm test. We examined the
      following four groups: patients with untreated thyrotoxic Graves' disease
      (untreated group), patients with Graves' disease treated with methimazole
      (treated group), patients in remission (remission group), and healthy volunteers
      (control group). To trace the glycolytic process, we measured glycolytic
      metabolites (lactate and pyruvate) as well as purine metabolites (ammonia and
      hypoxanthine). In the untreated group, the levels of lactate, pyruvate, and
      ammonia released were remarkably higher than those in the control group.
      Hypoxanthine release also increased in the untreated group, but the difference
      among the patient groups was not statistically significant. The accelerated
      purine catabolism did not improve after 3 months of treatment with methimazole,
      but it was completely normalized in the remission group. This indicated that long
      term maintenance of thyroid function was necessary for purine catabolism to
      recover. We presume that an unbalanced ATP supply or conversion of muscle fiber
      type may account for the acceleration of the purine nucleotide cycle under
      thyrotoxicosis. Such acceleration of the purine nucleotide cycle is thought to be
      in part a protective mechanism against a rapid collapse of the ATP energy balance
      in exercising muscles of patients with hyperthyroidism.

PMID- 11344229
TI  - Recombinant human growth hormone and recombinant human insulin-like growth factor
      I diminish the catabolic effects of hypogonadism in man: metabolic and molecular
      effects.
AB  - Severe gonadal androgen deficiency can have profound catabolic effects in man.
      Hypogonadal men develop a loss of lean body mass, increased adiposity, and
      decreased muscle strength despite normal GH and insulin-like growth factor I (IGF
      I) concentrations. We designed these studies to investigate whether GH or IGF-I
      administration to male subjects with profound hypogonadism can diminish or
      abolish the catabolic effects of testosterone deficiency. Moreover, we also
      examined the nature of the interactions among GH, IGF-I, and androgens in
      specific genes of the im system. A group of 13 healthy subjects (mean age, 22 +/-
      1 yr) was studied at baseline (D1) and 10 weeks after being made hypogonadal
      using a GnRH analog (GnRHa; D2). At 6 weeks from baseline they were started on
      either recombinant human (rh) IGF-I (60 microg/kg, sc, twice daily) or rhGH (12.5
      microg/kg, sc, daily) for 4 weeks. On each study day subjects had infusions of L
      [(13)C]leucine; indirect calorimetry; isokinetic dynamometry of the knee
      extensors; determination of body composition (dual energy x-ray absortiometry)
      and hormone and growth factor concentrations, as well as percutaneous muscle
      biopsies. Their data were compared with those of previously studied male subjects
      who received only GNRHA: Administration of rhIGF-I and rhGH to the hypogonadal
      men had similar effects on whole body metabolism, with maintenance of protein
      synthesis rates, fat oxidation rates, and fat-free mass compared with the
      eugonadal state, preventing the decline observed with hypogonadism alone. This
      was further amplified by the molecular assessment of important genes in muscle
      function. During rhIGF-I treatment, im expression of IGF-I declined, and IGF
      binding protein-4 increased, similar to the changes during GnRHa alone. However,
      rhGH administration was associated with a marked increase in IGF-I and androgen
      receptor messenger ribonucleic acid concentrations in skeletal muscle with a
      reciprocal decline in IGF-binding protein-4 expression in the hypogonadal men.
      The gene expression for myostatin did not change. These effects were accompanied
      by a much greater increase in plasma IGF-I concentrations after rhIGF-I (225 +/-
      32 vs. 768 +/- 117 microg/L) compared with the concentrations achieved during
      rhGH (217 +/- 20 vs. 450 +/- 19 microg/L). We conclude that 1) rhGH and rhIGF-I
      both may be beneficial in preserving lean body mass and sustaining rates of
      protein synthesis during states of severe androgen deficiency in man; 2) GH may
      affect the im IGF system via an a paracrine, local production of IGF-I; 3)
      androgens may be necessary for the full anabolic effect of GH/IGF-I in man. These
      hormones, particularly GH, may play a role in the treatment of hypogonadal men
      rendered hypogonadal pharmacologically or those unable to take full testosterone
      replacement. The latter requires further study.

PMID- 11344230
TI  - The quantification of gluconeogenesis in healthy men by (2)H2O and [2
      (13)C]glycerol yields different results: rates of gluconeogenesis in healthy men
      measured with (2)H2O are higher than those measured with [2-(13)C]glycerol.
AB  - The quantification of gluconeogenesis (GNG) by (2)H2O and [2-(13)C]glycerol and
      the mass isotopomer dilution analysis of glucose does not involve assumptions
      regarding the enrichment of the oxaloacetate precursor pool. To compare these two
      methods we measured GNG in six healthy postabsorptive males under identical,
      strictly standardized, eucaloric conditions, once after oral administration of
      (2)H2O and once during a primed continuous infusion of [2-(13)C]glycerol.
      Endogenous glucose production (EGP) was measured by infusion of [6,6
      (2)H(2)]glucose. EGP was not different after (2)H2O administration or during [2
      (13)C]glycerol infusion (12.2 +/- 0.7 vs. 11.7 +/- 0.3 micromol/kg.min). However,
      GNG measured after (2)H2O administration was significantly higher than that
      during [2-(13)C]glycerol infusion (7.4 +/- 0.7 vs. 4.9 +/- 0.6 micromol/kg.min; P
      = 0.03), representing approximately 60% and 41% of EGP, respectively. The (2)H2O
      study was repeated during primed continuous infusion of unlabeled glycerol,
      showing that infusion of glycerol at the rate used in the [2-(13)C]glycerol
      method does not affect the measurement of GNG with (2)H2O, viz. 7.4 +/- 0.7
      without glycerol vs. 7.6 +/- 0.9 micromol/kg.min with glycerol, representing
      approximately 60% vs. 62% of EGP. In conclusion, GNG measured by (2)H(2)O yields
      higher results than those measured by [2-(13)C]glycerol. This discrepancy is not
      merely caused by infusion of glycerol per se. Rather, the discrepancy between
      both methods probably relates to conceptual problems in underlying assumptions in
      one or both methods.

PMID- 11344231
TI  - Carcinoid syndrome, acromegaly, and hypoglycemia due to an insulin-secreting
      neuroendocrine tumor of the liver.
AB  - We report a patient with a hepatic neuroendocrine tumor showing an extraordinary
      change of the tumor's humoral manifestations from a clinically documented
      extrapituitary acromegaly and a typical carcinoid syndrome toward a
      hyperinsulinemic hypoglycemia syndrome. At the primary manifestation of the
      tumor, an increased serum level of insulin-like growth factor I due to
      overproduction of GHRH and an increased urinary excretion of 5
      hydroxyindoleacetic acid were found. The clinical manifestation of the GHRH
      excess was an arthralgia, which resolved completely after operative tumor
      debulking and normalization of insulin-like growth factor I and GHRH serum
      levels. The secretion of serotonin from the tumor resulted in a typical carcinoid
      syndrome including right-sided valvular heart disease. On the later course of the
      disease, the humoral manifestations of the tumor were supplemented by the
      secretion of insulin, leading to recurrent severe hyperinsulinemic hypoglycemia.
      The hepatic origin of hyperinsulinism was demonstrated by selective arterial
      calcium stimulation. Moreover, tumor cells revealed insulin and C-peptide
      immunoreactivity in the immunohistochemical analysis. The patient died 8 yr after
      the initial diagnosis of the tumor, and a carefully performed autopsy procedure
      confirmed the absence of any extrahepatic tumor manifestation.

PMID- 11344232
TI  - Inhibin/activin betaB-subunit expression in pheochromocytomas favors benign
      diagnosis.
AB  - Malignancy of pheochromocytomas is difficult to estimate on the basis of
      histopathological features. Good prognostic markers are not available. In our
      search for new markers to differentiate malignant pheochromocytomas from benign
      ones we tested the value of inhibin/activin subunit expression. Inhibins are
      heterodimeric glycoproteins consisting of an alpha-subunit and either a betaA- or
      a betaB-subunit. Activins are composed of beta-subunits only.
      Immunohistochemically inhibin/activin betaB-subunit was strongly positive in the
      normal adrenal medulla, but the cortex was negative. A striking difference was
      found in inhibin/activin betaB expression between benign and malignant
      pheochromocytomas. The majority of benign adrenal tumors (27 of 30) showed strong
      or moderate immunoreactivity, whereas all seven malignant tumors were negative or
      only weakly positive for inhibin/activin betaB-subunit. The percentage of
      positively staining cells varied greatly in extraadrenal pheochromocytomas and in
      those benign tumors that showed over 5 mitoses/10 high power fields, necrosis, or
      capsular or vascular invasion, here called borderline tumors. Inhibin/activin
      betaB messenger ribonucleic acid was also found in pheochromocytomas. However, no
      significant differences in messenger ribonucleic acid levels were found in
      various types of tumors. Weak immunohistochemical positivity for inhibin/activin
      betaA-subunit was detected in the adrenal cortex, but the medulla and most of the
      pheochromocytomas were negative. Our data show that inhibin/activin betaB-subunit
      is expressed in normal adrenal medullary cells. Strong staining is found in most
      benign adrenal pheochromocytomas, whereas malignant tumors are almost negative.
      This suggests that loss of inhibin/activin betaB-subunit expression in
      pheochromocytomas may be used as an indicator of malignant potential.

PMID- 11344233
TI  - The antral mucosa as a new site for endocrine tumors in multiple endocrine
      neoplasia type 1 and Zollinger-Ellison syndromes.
AB  - Carcinoid tumors were identified in the antro-pyloric mucosa of four patients
      with multiple endocrine neoplasia type 1 (MEN-1)/Zollinger-Ellison syndrome,
      accounting for 8.7% of 46 patients with this condition examined by endoscopy and
      histology. In contrast, no tumors were found in the antral biopsies from 124
      cases of sporadic Zollinger-Ellison syndrome (P < 0.001), indicating a prominent
      role for the MEN-1 gene defects in tumor development. Immunohistochemically the
      tumors did not express the hormones produced by antral endocrine cells (gastrin,
      somatostatin, serotonin). In contrast, two of them were diffusely immunoreactive
      for the isoform 2 of the vesicular monoamine transporter (VMAT-2), a marker
      specific for the gastric nonantral enterochromaffin-like (ECL) cells. In one of
      these patients a second antral VMAT-2-positive carcinoid was seen 21 months after
      the first diagnosis. The other two antral carcinoids were unreactive for VMAT-2.
      Multiple ECL cell tumors were found in the gastric body-fundus mucosa of the two
      patients with VMAT-2-positive, but not in those with VMAT-2-negative, antral
      carcinoids. In one case, the former tumors were diagnosed 22 months after the
      detection of the antral tumor. We conclude that the antral mucosa is an
      additional tissue that may harbor endocrine tumors in MEN-1 syndrome. These
      tumors did not express the phenotype of normal antral endocrine cells and, in at
      least two cases, were identified as ectopic ECL cell carcinoids.

PMID- 11344234
TI  - Cyclooxygenase-2 expression and prostaglandin E(2) synthesis are up-regulated in
      carcinomas of the cervix: a possible autocrine/paracrine regulation of neoplastic
      cell function via EP2/EP4 receptors.
AB  - The prevalence of cervical cancer in South African women is reported as being the
      highest in the world, occurring, on the average, in 60 of every 100,000 women.
      Cervical cancer is thus considered an important clinical problem in sub-Saharan
      AFRICA: Recent studies have suggested that epithelial tumors may be regulated by
      cyclooxygenase (COX) enzyme products. The purpose of this study was to determine
      whether cyclooxygenase-2 (COX-2) expression and PGE(2) synthesis are up-regulated
      in cervical cancers. Real-time quantitative RT-PCR and Western blot analysis
      confirmed COX-2 ribonucleic acid and protein expression in all cases of squamous
      cell carcinoma (n = 8) and adenocarcinoma (n = 2) investigated. In contrast,
      minimal expression of COX-2 was detected in histologically normal cervix (n = 5).
      Immunohistochemical analyses localized COX-2 expression and PGE(2) synthesis to
      neoplastic epithelial cells of all squamous cell (n = 10) and adenocarcinomas (n
      = 10) studied. Immunoreactive COX-2 and PGE(2) were also colocalized to
      endothelial cells lining the microvasculature. Minimal COX-2 and PGE(2)
      immunoreactivity were detected in normal cervix (n = 5). To establish whether
      PGE(2) has an autocrine/paracrine effect in cervical carcinomas, we investigated
      the expression of two subtypes of PGE(2) receptors, namely EP2 and EP4, by real
      time quantitative RT-PCR. Expression of EP2 and EP4 receptors was significantly
      higher in carcinoma tissue (n = 8) than in histologically normal cervix (n = 5; P
      < 0.01). Finally, the functionality of the EP2/EP4 receptors was assessed by
      investigating cAMP generation after in vitro culture of cervical cancer biopsies
      and normal cervix in the presence or absence of 300 nmol/L PGE(2). cAMP
      production was detected in all carcinoma tissue after treatment with exogenous
      PGE(2) and was significantly higher in carcinoma tissue (n = 7) than in normal
      cervix (n = 5; P < 0.05). The fold induction of cAMP in response to PGE(2) was
      51.1 +/- 12.3 in cervical carcinoma tissue compared with 5.8 +/- 2.74 in normal
      cervix. These results confirm that COX-2, EP2, and EP4 expression and PGE(2)
      synthesis are up-regulated in cervical cancer tissue and suggest that PGE(2) may
      regulate neoplastic cell function in cervical carcinoma in an autocrine/paracrine
      manner via the EP2/EP4 receptors.

PMID- 11344235
TI  - 5alpha-reductases in human breast carcinoma: possible modulator of in situ
      androgenic actions.
AB  - The expression of 5alpha-reductase types 1 and 2 was examined in human breast
      carcinoma using immunohistochemistry and RT-PCR. Immunoreactivity for 5alpha
      reductase isozymes was also correlated with various clinicopathological
      parameters to examine possible local regulatory mechanisms of sex steroids,
      including progesterone and androgens, in human breast carcinoma tissues.
      Immunoreactivity for 5alpha-reductase type 1 was detected in the cytoplasm and
      possibly in the nuclear membrane of tumor cells in 35 of 60 invasive ductal
      carcinomas (58%), and type 2 signal was detected in 9 of these 60 cases (15%).
      The results from RT-PCR (n = 8) were consistent with those from
      immunohistochemistry. A significant positive correlation was detected between
      5alpha-reductase type 1 immunoreactivity and androgen and progesterone receptor A
      or B labeling indexes, and immunoreactivities of 5alpha-reductase type 2, 17beta
      hydroxysteroid dehydrogenase type 5, or 3beta-hydroxysteroid dehydrogenase, which
      recognizes both types I and II. An inverse correlation was detected between
      5alpha-reductase type 1 immunoreactivity and tumor size, histological grade, or
      Ki-67 labeling index. 5alpha-Reductase type 2 immunoreactivity was significantly
      correlated with 17beta-hydroxysteroid dehydrogenase type 5 immunoreactivity, but
      not with other parameters. This study suggests that 5alpha-reductase type 1 is
      mainly expressed in human breast carcinoma, which may play an important role in
      the in situ production and actions of the potent androgen, 5alpha
      dihydrotestosterone, including inhibition of cancer cell proliferation, in
      hormone-dependent human breast carcinoma.

PMID- 11344236
TI  - Expression and cellular localization of estrogen receptors alpha and beta in the
      human fetus.
AB  - Estrogens exert various biological effects by acting through their native
      receptors, two of which have been identified to date: estrogen receptors alpha
      (ERalpha) and beta (ERbeta). In this study we examined the expression and
      cellular localization of ERalpha and ERbeta in various human fetal tissues by
      semiquantitative RT-PCR (13 and 20 gestational weeks) and immunohistochemistry
      (13, 20, and 38 gestational weeks), respectively, to study the possible effects
      of estrogens on human fetal tissues during development. Relatively high levels of
      ERbeta expression were detected in various human fetal tissues, whereas those
      tissues expressing ERbeta had markedly lower levels of ERalpha expression. ERbeta
      messenger ribonucleic acid expression was especially high in the adrenal gland.
      ERbeta-immunoreactive protein was localized to the definitive zone, but not in
      the fetal zone, of the adrenal cortex. Although low levels of ERbeta messenger
      ribonucleic acid were present in the brain, heart, lung, and kidney, ERbeta
      immunoreactivity was not detected in these tissues. These results suggest that
      the effects of estrogens in these tissues are predominantly mediated through
      ERbeta. ERbeta immunoreactivity was detected in Sertoli cells and spermatogonia
      in the male reproductive tract and in germ cells in the fetal testis and
      epididymis. In the female reproductive tract, both ERalpha and ERbeta were
      immunopositive in epithelium of the oviduct. The results of the present study
      have demonstrated the possible sites for estrogenic action in the human fetus and
      suggest that the effects of estrogen via ERbeta may play important roles in human
      fetal development, especially in the definitive zone of the adrenal cortex, and
      in the reproductive tissues of the developing fetus.

PMID- 11344237
TI  - Polymorphism of the aromatase gene in postmenopausal Italian women: distribution
      and correlation with bone mass and fracture risk.
AB  - Conversion of C(19) steroids to estrogens is catalyzed by the aromatase enzyme.
      Inactivating mutations of the aromatase gene are associated with decreased bone
      mineral density in both men and women. Genetic studies suggest that several genes
      contribute to the regulation of bone mass via interaction with the modeling and
      remodeling processes. Among these genes, the aromatase gene is a potential
      candidate to be evaluated for segregation with bone metabolism and bone mass. A
      tetranucleotide simple tandem repeat polymorphism in intron 4 at the human
      aromatase cytochrome P-450 gene has been recently described. In the present study
      we evaluated the distribution of this polymorphism in a cohort of Italian
      postmenopausal women, both normal and osteoporotic. We observed that the NN
      genotype was significantly more frequent in nonosteoporotic women than in
      osteoporotic women (72.7% vs. 27.2%), whereas the DN genotype was significantly
      more represented in osteoporotic women (90.48% vs. 9.5%; Pearson's chi(2) test =
      42.8; df = 10; P = or < 0.01). The allele containing the longer TTTA repeats was
      statistically more represented in nonosteoporotic women (Pearson's chi(2) test =
      19.14; df = 2; P = 0.00007). In addition, women with a high number of TTTA
      repeats had a significantly higher lumbar bone mineral density than women with
      alleles containing 8-11 TTTA repeats (P = 0.03). Finally, considering the spine
      fractures, a significantly higher incidence was observed in women with shorter
      TTTA repeats than in those with longer TTTA repeats (Pearson's chi(2) test = 7.3;
      df = 2; P = 0.02), equivalent to a relative risk of 4.1 (95% confidence interval,
      1.19-13.87). In conclusion, the aromatase gene can be one of the several genes
      potentially involved in the maintenance of bone mass and in the regulation of
      bone mass loss.

PMID- 11344238
TI  - The N363S polymorphism of the glucocorticoid receptor: potential contribution to
      central obesity in men and lack of association with other risk factors for
      coronary heart disease and diabetes mellitus.
AB  - Considerable evidence suggests that diabetes mellitus and hypertension are
      influenced by genetic factors. Studies in humans have associated glucocorticoid
      receptor (GR) polymorphisms with high blood pressure, insulin sensitivity, body
      mass index, increased visceral fat, and variations in tissue-specific steroid
      sensitivity. The N363S polymorphism of the GR results in an asparagine to serine
      amino acid substitution in a modulatory region of the receptor. Phosphorylation
      of serine residues in this region has been shown to enhance transactivation of GR
      responsive genes. The aim of this study was to investigate the association
      between the 363S allele and risk factors for coronary heart disease and diabetes
      mellitus in a population of European origin living in the northeast of the United
      KINGDOM: Blood samples from 135 males and 240 females were characterized for 363
      allele status. The overall frequency of the 363S allele was 3.0%, 23
      heterozygotes (7 males and 16 females) but no 363S homozygotes were identified.
      The data show a significant association of the 363S allele with increased waist
      to hip ratio in males but not females. This allele was not associated with blood
      pressure, body mass index, serum cholesterol, triglycerides, low-density
      lipoprotein and high-density lipoprotein cholesterol levels, and glucose
      tolerance status. The results of this study suggest that this GR polymorphism may
      contribute to central obesity in men. Further studies are required to elucidate
      the properties of GR(363S) at a molecular level.

PMID- 11344239
TI  - Tumor necrosis factor-alpha expression in human uterine leiomyoma and its down
      regulation by progesterone.
AB  - Although tumor necrosis factor-alpha (TNFalpha) has been shown mainly to inhibit
      proliferation and induce apoptosis in a variety of cells, no information is
      available regarding whether human leiomyoma cells express TNFalpha. In the
      present study, we examined the expression of TNFalpha in leiomyomas, in
      comparison with that in the adjacent normal myometrium, using immunohistochemical
      staining and Western immunoblot analysis with a polyclonal antibody to human
      TNFalpha. Furthermore, we investigated the effect of sex steroid hormones on
      TNFalpha expression in leiomyoma cells cultured under serum-free, phenol red-free
      conditions. Immunohistochemical staining showed that TNFalpha expression in
      leiomyoma cells was higher than that in the adjacent normal myometrial cells,
      being more abundant in the proliferative phase than in the secretory,
      progesterone (P4)-dominated, phase of the menstrual cycle. TNFalpha expression in
      leiomyoma cells in pregnant uterus was scarce. Western immunoblot analyses of
      leiomyoma and normal myometrial tissue extracts revealed that TNFalpha, with a
      molecular mass of 17.3 kDa, was abundantly present in leiomyoma tissue extracts,
      relative to normal myometrial tissue extracts, and that TNFalpha expression in
      leiomyoma cells was most abundant in the proliferative phase of the menstrual
      cycle, less abundant in the secretory phase, and least abundant in pregnant
      uterus; whereas no such changes in TNFalpha expression were noted in the normal
      myometrium. In monolayer cultures of uterine leiomyoma cells under serum-free
      conditions, addition of P4 (3.18 x 10(-7) mol/L) resulted in a decrease in
      TNFalpha expression in the cells, relative to that in control cultures, whereas
      treatment with 17beta-estradiol (3.67 x 10(-8) mol/L) did not affect the TNFalpha
      expression in the cells. The concentrations of sex steroids used were within the
      physiological tissue concentrations noted in leiomyoma and myometrium. The
      present results suggest that the abundant expression of TNFalpha may be a
      molecular basis characteristic of leiomyomas in the human uterus and that P4 may
      play a vital role in down-regulating the expression of TNFalpha in human uterine
      leiomyoma.

PMID- 11344240
TI  - Human breast adipocytes express interleukin-6 (IL-6) and its receptor system:
      increased IL-6 production by beta-adrenergic activation and effects of IL-6 on
      adipocyte function.
AB  - Adipocytes produce the inflammatory cytokine interleukin-6 (IL-6); however, it is
      not known whether these cells express the IL-6 receptor system, how the secretion
      of this cytokine is regulated, and whether it has a function within adipose
      tissue. Using cultured human breast adipocytes, we investigated the expression of
      IL-6 and its receptor system, the effects of IL-6 on main adipocyte functions,
      and the regulation of IL-6 secretion by catecholamines and glucocorticoids. In
      the culture system, immunohistochemistry demonstrated expression of IL-6 and its
      receptor system, consisting of the ligand-binding IL-6 receptor and the signal
      transducing protein gp130, in mature adipocytes, but not in undifferentiated
      adipocyte precursor cells. In freshly isolated adipocytes, RT-PCR detected
      messenger ribonucleic acids encoding the above proteins. Chronic incubation of
      adipocytes with 1 nmol/L IL-6 during adipose differentiation reduced glycero-3
      phosphate dehydrogenase (GPDH) activity, a marker of adipocyte differentiation,
      and triglyceride synthesis to 67 +/- 9% of the basal level (mean +/- SEM; P <
      0.05) only on day 21. Incubation of differentiated adipocytes with 10 nmol/L IL-6
      for 24 h also resulted in a reduction of GPDH activity to 81 +/- 5% (P < 0.05).
      On the other hand, 24-h exposure to 10 nmol/L IL-6 increased basal glycerol
      release by 42 +/- 12% (P < 0.01) and isoproterenol-induced glycerol release by 21
      +/- 6% (P < 0.05). The same concentration of IL-6, however, did not alter basal
      or insulin-stimulated glucose transport. IL-6 secretion was acutely and
      chronically stimulated by 1 micromol/L isoproterenol (peak of 6.2-fold after 3 h;
      P < 0.001) and only moderately suppressed by 100 nmol/L cortisol (-36 +/- 10%; P
      < 0.001). In conclusion, human breast adipocytes release substantial amounts of
      IL-6 and express IL-6 receptor and gp130. The secretion of IL-6 by adipocytes is
      strongly stimulated by beta-adrenergic activation and is modestly suppressed by
      glucocorticoids. IL-6 reduces GPDH activity and stimulates lipolysis, suggesting
      an autocrine/paracrine role of this cytokine in human adipose breast tissue.

PMID- 11344241
TI  - Dyslipemia in familial partial lipodystrophy caused by an R482W mutation in the
      LMNA gene.
AB  - Lipatrophic diabetes, also referred to as familial partial lipodystrophy, is a
      rare disease that is metabolically characterized by hypertriglyceridemia and
      insulin resistance. Affected patients typically present with regional loss of
      body fat and muscular hypertrophic appearance. Variable symptoms may comprise
      pancreatitis and/or eruptive xanthomas due to severe hypertriglyceridemia,
      acanthosis nigricans, polycystic ovaria, and carpal tunnel syndrome. Mutations
      within the LMNA gene on chromosome 1q21.2 were recently reported to result in the
      phenotype of familial partial lipodystrophy. The genetic trait is autosomal
      dominant. We identified a family with partial lipodystrophy carrying the R482W
      (Arg(482)Trp) missense mutation within LMNA. Here we present the lipoprotein
      characteristics in this family in detail. Clinically, the loss of sc fat and
      muscular hypertrophy especially of the lower extremities started as early as in
      childhood. Acanthosis and severe hypertriglyceridemia developed later in life,
      followed by diabetes. The characterization of the lipoprotein subfractions
      revealed that affected children present with hyperlipidemia. The presence and
      severity of hyperlipidemia seem to be influenced by age, apolipoprotein E
      genotype, and the coexistence of diabetes mellitus. In conclusion, dyslipemia is
      an early and prominent feature in the presented lipodystrophic family carrying
      the R482W mutation within LMNA.

PMID- 11344242
TI  - Regulation of glucocorticoid receptor alpha and beta isoforms and type I 11beta
      hydroxysteroid dehydrogenase expression in human skeletal muscle cells: a key
      role in the pathogenesis of insulin resistance?
AB  - Glucocorticoid excess frequently results in obesity, insulin resistance, glucose
      intolerance, and hypertension and may be the product of altered glucocorticoid
      hormone action. Tissue sensitivity to glucocorticoid is regulated by the
      expression of glucocorticoid receptor isoforms (GRalpha and GRbeta) and 11beta
      hydroxysteroid dehydrogenase type I (11betaHSD1)-mediated intracellular synthesis
      of active cortisol from inactive cortisone. We have analyzed the expression of
      GRalpha, GRbeta, and 11betaHSD1 and their hormonal regulation in skeletal
      myoblasts from men (n = 14) with contrasting levels of adiposity and insulin
      resistance. Immunohistochemical, Northern blot, and Western blot analysis
      indicated abundant expression of GRalpha and 11betaHSD1 under basal conditions.
      The apparent K(m) and maximum velocity for the conversion of cortisone to
      cortisol were 440 +/- 14 nmol/L and 75 +/- 7 pmol/mg protein.h and 437 +/- 16
      nmol/L and 33 +/- 6 pmol/mg protein.h (mean +/- SEM; n = 4) in the presence and
      absence of 20% serum. Incubation of myoblasts with increasing concentrations of
      glucocorticoid (50-1000 nmol/L) resulted in a dose-dependent decline in GRalpha
      expression and a dose-dependent increase in GRbeta expression. 11betaHSD1
      activity was sensitively up-regulated by increasing concentrations of
      glucocorticoid (50-1000 nmol/L: P < 0.05). Abolition of these effects by the GR
      antagonist, RU38486, indicates that regulation of GRalpha, GRbeta, and 11betaHSD1
      expression is mediated exclusively by the GRalpha ligand-binding variant. In
      contrast, 11betaHSD1 was down-regulated by insulin (20-100 mU/mL: P < 0.01) in
      the presence of 20% serum, whereas incubation with insulin under serum-free
      conditions resulted in a dose-dependent increase in 11betaHSD1 activity (P <
      0.05). Incubation with insulin-like growth factor I resulted in a similar pattern
      of 11betaHSD1 activity. Although neither testosterone nor androstenedione (5-200
      nmol/L) affected 11betaHSD1 activity, incubation of myoblasts with
      dehydroepiandrosterone (500 nmol/L) resulted in a decline in 11betaHSD1 activity
      (P < 0.05). These data suggest that glucocorticoid hormone action in skeletal
      muscle is determined principally by autoregulation of GRalpha, GRbeta, and
      11betaHSD1 expression by the ligand-binding GRalpha isoform. Additionally,
      insulin and insulin-like growth factor I regulation of 11betaHSD1 may represent a
      novel mechanism that maintains insulin sensitivity in skeletal muscle tissue by
      diminishing glucocorticoid antagonism of insulin action.

PMID- 11344243
TI  - Estrogen receptors alpha and beta are differentially expressed in developing
      human bone.
AB  - Estrogen plays an essential role in the development and maintenance of the
      skeleton; its effects are mediated via interactions with two estrogen receptor
      (ER) subtypes, alpha and beta. The aim of this study was to establish the
      cellular distribution of ERalpha and ERbeta in neonatal human rib bone. ERalpha
      and ERbeta immunoreactivity was seen in proliferative and prehypertrophic
      chondrocytes in the growth plate, with lower levels of expression in the late
      hypertrophic zone. Different patterns of expression of the two ERs were seen in
      bone. In cortical bone, intense staining for ERalpha was observed in osteoblasts
      and osteocytes adjacent to the periosteal-forming surface and in osteoclasts on
      the opposing resorbing surface. In cancellous bone, ERbeta was strongly expressed
      in both osteoblasts and osteocytes, whereas only low expression of ERalpha was
      seen in these areas. Nuclear and cytoplasmic staining for ERbeta was apparent in
      osteoclasts. These observations demonstrate distinct patterns of expression for
      the two ER subtypes in developing human bone and indicate functions in both the
      growth plate and mineralized bone. In the latter, ERalpha is predominantly
      expressed in cortical bone, whereas ERbeta shows higher levels of expression in
      cancellous bone.

PMID- 11344244
TI  - Extrathyroidal manifestations of Graves' disease: the thyrotropin receptor is
      expressed in extraocular, but not cardiac, muscle tissues.
AB  - The existence of an autoantigen common to Graves' disease and its associated
      extrathyroidal manifestations has been proposed. As the TSH receptor (TSHR) is
      the primary target for autoimmunity against the thyroid in Graves' disease, much
      effort has gone into investigating the role of TSHR messenger ribonucleic acid
      (mRNA) transcripts in extrathyroidal tissue, particularly in the orbit. A high
      stringency RT-PCR technique had previously been employed by our laboratory to
      demonstrate the presence of full-length and splice variant TSHR mRNA in
      extraocular muscle (EOM). This technique demonstrated selective amplification of
      TSHR mRNA transcripts in thyroid and EOM, but not in abdominal muscle, kidney, or
      brain tissue. We used this technique in the present study to investigate the
      reported presence of TSHR mRNA transcripts in cardiac tissue. After removal of
      all visible fat from muscle tissues, high stringency RT-PCR was performed, and we
      found no TSHR transcripts in the muscle of any chamber of the normal human heart.
      In addition, in situ hybridization on fresh-frozen and paraffin-embedded sections
      confirmed the presence of TSHR transcripts in thyroid and EOM, but not in
      abdominal or cardiac muscle. These findings support the hypothesis that the TSHR
      is a shared antigen in the thyroid and EOM, but not in cardiac muscle.

PMID- 11344245
TI  - Mutation screening of the neurogenin-3 gene in autosomal dominant diabetes.
AB  - We investigated whether genetic variability in neurogenin-3, a basic helix-loop
      helix transcription factor that is expressed in the developing pancreas,
      contributes to the etiology of maturity-onset diabetes of the young or other
      forms of autosomal dominant diabetes. Ninety-one probands of families with
      autosomal dominant diabetes were screened for neurogenin-3 mutations by dideoxy
      fingerprinting. Three sequence differences were identified: a polymorphism not
      affecting the amino acid sequence (L75L), a CA insertion/deletion in intron 1 (
      44ins/del), and a C to T transition causing a serine to phenylalanine
      substitution (S199F). None of these sequence differences were more frequent in
      the family probands than in 179 nondiabetic controls. In contrast, allele 199F
      was weakly, but significantly, associated with common type 2 diabetes (199F
      frequencies = 0.436 in 132 cases with type 2 diabetes vs. 0.346 in the family
      probands and 0.346 in controls; P = 0.05). The relative risk of type 2 diabetes
      for 199F carriers was 1.7 (95% confidence interval, 1.04-2.7). We conclude that
      sequence differences in the neurogenin-3 gene do not play a major role in the
      development of autosomal dominant diabetes. Rather, they might contribute to
      common type 2 diabetes, although this finding must be replicated in other
      populations.

PMID- 11344246
TI  - Kallikrein 4 (KLK4), a new member of the human kallikrein gene family is up
      regulated by estrogen and progesterone in the human endometrial cancer cell line,
      KLE.
AB  - Endometrial cancer is the fourth most common female malignancy in women in
      developed countries. Estrogen, and to a lesser degree, progesterone, regulate
      specific target genes that are involved in endometrial tumorigenesis. A family of
      proteases involved in cellular proliferation, extracellular matrix degradation
      and thus, implicated in tumorigenesis, and regulated by estrogen and progesterone
      in a number of systems, are the tissue kallikreins (KLKs). KLK4, a new member of
      the KLK gene family, was found to be expressed to varying levels in a number of
      endometrial cancer cell lines- HEC1A, HEC1B, Ishikawa, RL95-2 and KLE- at both
      the mRNA and protein level. On the addition of 10 nmol/L estradiol, progesterone,
      or a combination of both over a 48 h period, an increase in the intracellular
      protein levels of K4 were observed when compared to the control (untreated)
      cells. We have also identified a novel KLK4 transcript with a complete exon 4
      deletion. The significance of this alternative transcript, which would give rise
      to a truncated protein without a serine residue (which is essential for catalytic
      activity), is yet to be established. These cell lines now provide a model system
      to study the role of KLK4 and the molecular mechanisms of KLK4 regulation by
      estrogen and progesterone, in endometrial tumorigenesis.

PMID- 11344248
TI  - Graves' ophthalmopathy.

PMID- 11344250
TI  - Noninsulinoma pancreatogenous hypoglycemia in adults: presentations of two cases.

PMID- 11344251
TI  - Vitamin D receptor status in parathyroid adenomas.

PMID- 11344253
TI  - Oscillation may play a role in time domain central auditory processing.
AB  - To study how sound intensity altered the temporal response pattern of a unit, we
      recorded from 92 single neurons in the inferior colliculus (IC) of the little
      brown bat and investigated their firing patterns in response to brief tone pulses
      (2 msec duration) at the characteristic frequency of the unit over a wide dynamic
      range (10-90 dB sound pressure level). We found two unusual response
      characteristics at high sound levels in approximately one-third of the IC neurons
      investigated. For 16 IC neurons (17%), an increase in sound level not only
      elicited a shorter response latency and an increase in spike count but also
      transformed the firing pattern of the unit from phasic to periodic; this pattern
      was more pronounced at higher sound levels. The firing periodicity was unit
      specific, ranging from 1.3 to 6.7 msec. Twenty-seven IC neurons (29%) exhibited a
      longer response latency at higher sound levels compared with lower sound levels
      [i.e., paradoxical latency shift (PLS)]. The majority of this population showed a
      one or more quantum increase in latency when sound level was elevated. The
      quantum shift was also unit specific, ranging from 1.2 to 8.2 msec. We further
      investigated the firing patterns of 14 IC neurons showing PLS before, during, and
      after iontophoretic application of bicuculline. For 12 of these neurons, drug
      application abolished the PLS and transformed the firing patterns of the unit at
      high sound levels from phasic into sustained periodic discharges. Our results
      suggest that neural oscillation in combination with ordinary inhibition may be
      responsible for the creation of PLSs shown previously to be important for
      temporal information processing.

PMID- 11344254
TI  - Increased expression of neuronal nitric oxide synthase spliced variants in
      reactive astrocytes of amyotrophic lateral sclerosis human spinal cord.
AB  - The expression of three different neuronal nitric oxide synthase (nNOS) spliced
      variants, named nNOSalpha, nNOSbeta, and nNOSgamma, was investigated in the
      spinal cord of control and both familiar and sporadic amyotrophic lateral
      sclerosis (FALS and SALS) patients. Western blot analysis showed a consistent
      increase in nNOS expression in six SALS patients compared with controls when
      antibodies recognizing both nNOSalpha and nNOSbeta, or nNOSalpha, nNOSbeta, and
      nNOSgamma were used, whereas no change was observed when a selective anti
      nNOSalpha antibody was used. Immunoreactivity signal for nNOSalpha-beta-gamma and
      nNOSalpha-beta was equally present in ventral horn neurons of control and ALS
      spinal cord but was dramatically increased in reactive astrocytes of the ventral
      horn and white matter in both FALS and SALS. nNOSalpha signal was equally
      expressed in motor neurons of normal and ALS spinal cord but was not evident in
      astrocytes. This finding indicates that nNOSbeta and nNOSgamma spliced variants
      are upregulated in reactive astrocytes in ALS. This may contribute to the
      peroxynitrite-mediated oxidative damage involved in the pathogenesis of both FALS
      and SALS.

PMID- 11344255
TI  - Free 3-nitrotyrosine causes striatal neurodegeneration in vivo.
AB  - Peroxynitrite formation has been demonstrated in several neurodegenerative
      disorders; thus far, protein nitration and consequent alterations in protein
      function are implicated as mechanistic events. Free 3-nitrotyrosine (free-3NT) is
      also elevated in these settings; a neurotoxic role for this modified amino acid
      has not been investigated. We tested the hypothesis that free-3NT is neurotoxic
      in vivo, using a mouse model of striatal degeneration. The neurodegenerative
      effects of the dopaminergic neurotoxin 6-hydroxydopamine (6-OHDA) (unilateral
      intrastriatal injection, 64 nmol) were compared with free-3NT (32 nmol) or free
      tyrosine (free-TYR) (32 nmol). 6-OHDA-treated mice exhibited significant
      ipsilateral turning behavior after d-amphetamine challenge, indicative of
      unilateral striatal injury (ipsilateral-contralateral turning differential, 21.1
      +/- 6.8). Significant turning behavior was also observed in free-3NT-treated mice
      but not in free-tyrosine-treated mice (free-3NT, 16.0 +/- 3.9; free-TYR, 1 +/-
      2.7; p < 0.01). Immunohistochemistry was used to evaluate striatal tyrosine
      hydroxylase (TH) content. 6-OHDA or free-3NT treatment caused severe reductions
      in TH immunoreactivity in injected striata compared with the contralateral
      hemisphere (injected/contralateral immunoreactivity ratio: 6-OHDA, 0.23 +/- 0.07;
      free-3NT, 0.49 +/- 0.02). Free-tyrosine treatment had no effect (1.03 +/- 0.09).
      Turning behavior was correlated with striatal TH ratio (p < 0.01). Furthermore,
      we observed a striking unilateral reduction in TH-positive cell body counts in
      the substantia nigra pars compacta of 6-OHDA- and free-3NT-treated mice
      (injected/contralateral cell count ratio: 6-OHDA, 0.40 +/- 0.04; free-3NT, 0.59
      +/- 0.02). Free-tyrosine treatment had no effect (1.05 +/- 0.04). No evidence for
      increased striatal protein incorporation of 3NT was observed in any treatment
      group. These data represent the first evidence that free-3NT can elicit
      neurodegenerative effects in vivo; free-3NT may have a causal role in
      neurodegenerative conditions.

PMID- 11344256
TI  - Top-down free-energy minimization on protein potential energy landscapes.
AB  - The hierarchical properties of potential energy landscapes have been used to gain
      insight into thermodynamic and kinetic properties of protein ensembles. It also
      may be possible to use them to direct computational searches for
      thermodynamically stable macroscopic states, i.e., computational protein folding.
      To this end, we have developed a top-down search procedure in which conformation
      space is recursively dissected according to the intrinsic hierarchical structure
      of a landscape's effective-energy barriers. This procedure generates an inverted
      tree similar to the disconnectivity graphs generated by local minima-clustering
      methods, but it fundamentally differs in the manner in which the portion of the
      tree that is to be computationally explored is selected. A key ingredient is a
      branch-selection algorithm that takes advantage of statistically predictive
      properties of the landscape to guide searches down the tree branches that are
      most likely to lead to the physically relevant macroscopic states. Using the
      computational folding of a beta-hairpin-forming peptide as an example, we show
      that such predictive properties indeed exist and can be used for structure
      prediction by free-energy global minimization.

PMID- 11344257
TI  - Mechanism for nucleic acid chaperone activity of HIV-1 nucleocapsid protein
      revealed by single molecule stretching.
AB  - The nucleocapsid protein (NC) of HIV type 1 is a nucleic acid chaperone that
      facilitates the rearrangement of nucleic acids into conformations containing the
      maximum number of complementary base pairs. We use an optical tweezers instrument
      to stretch single DNA molecules from the helix to coil state at room temperature
      in the presence of NC and a mutant form (SSHS NC) that lacks the two zinc finger
      structures present in NC. Although both NC and SSHS NC facilitate annealing of
      complementary strands through electrostatic attraction, only NC destabilizes the
      helical form of DNA and reduces the cooperativity of the helix-coil transition.
      In particular, we find that the helix-coil transition free energy at room
      temperature is significantly reduced in the presence of NC. Thus, upon NC
      binding, it is likely that thermodynamic fluctuations cause continuous melting
      and reannealing of base pairs so that DNA strands are able to rapidly sample
      configurations to find the lowest energy state. The reduced cooperativity allows
      these fluctuations to occur in the middle of complex double-stranded structures.
      The reduced stability and cooperativity, coupled with the electrostatic
      attraction generated by the high charge density of NC, is responsible for the
      nucleic acid chaperone activity of this protein.

PMID- 11344258
TI  - Five subunits are required for reconstitution of the cleavage and polyadenylation
      activities of Saccharomyces cerevisiae cleavage factor I.
AB  - Cleavage and polyadenylation of mRNA 3' ends in Saccharomyces cerevisiae requires
      several factors, one of which is cleavage factor I (CF I). Purification of CF I
      activity from yeast extract has implicated numerous proteins as functioning in
      both cleavage and/or polyadenylation. Through reconstitution of active CF I from
      separately expressed and purified proteins, we show that CF I contains five
      subunits, Rna14, Rna15, Pcf11, Clp1, and Hrp1. These five are necessary and
      sufficient for reconstitution of cleavage activity in vitro when mixed with CF
      II, and for specific polyadenylation when mixed with polyadenylation factor I,
      purified poly(A) polymerase, and poly(A) binding protein. Analysis of the
      individual protein-protein interactions supports an architectural model for CF I
      in which Pcf11 simultaneously interacts with Rna14, Rna15, and Clp1, whereas
      Rna14 bridges Rna15 and Hrp1.

PMID- 11344259
TI  - Requirement of the nicotinic acetylcholine receptor beta 2 subunit for the
      anatomical and functional development of the visual system.
AB  - In the mammalian visual system the formation of eye-specific layers at the
      thalamic level depends on retinal waves of spontaneous activity, which rely on
      nicotinic acetylcholine receptor activation. We found that in mutant mice lacking
      the beta2 subunit of the neuronal nicotinic receptor, but not in mice lacking the
      alpha4 subunit, retinofugal projections do not segregate into eye-specific areas,
      both in the dorso-lateral geniculate nucleus and in the superior colliculus.
      Moreover, beta2-/- mice show an expansion of the binocular subfield of the
      primary visual cortex and a decrease in visual acuity at the cortical level but
      not in the retina. We conclude that the beta2 subunit of the nicotinic
      acetylcholine receptor is necessary for the anatomical and functional development
      of the visual system.

PMID- 11344260
TI  - Targeted mutagenesis of Lis1 disrupts cortical development and LIS1
      homodimerization.
AB  - Lissencephaly is a severe brain malformation in humans. To study the function of
      the gene mutated in lissencephaly (LIS1), we deleted the first coding exon from
      the mouse Lis1 gene. The deletion resulted in a shorter protein (sLIS1) that
      initiates from the second methionine, a unique situation because most LIS1
      mutations result in a null allele. This mutation mimics a mutation described in
      one lissencephaly patient with a milder phenotype. Homozygotes are early lethal,
      although heterozygotes are viable and fertile. Most strikingly, the morphology of
      cortical neurons and radial glia is aberrant in the developing cortex, and the
      neurons migrate more slowly. This is the first demonstration, to our knowledge,
      of a cellular abnormality in the migrating neurons after Lis1 mutation. Moreover,
      cortical plate splitting and thalomocortical innervation are also abnormal.
      Biochemically, the mutant protein is not capable of dimerization, and enzymatic
      activity is elevated in the embryos, thus a demonstration of the in vivo role of
      LIS1 as a subunit of PAF-AH. This mutation allows us to determine a hierarchy of
      functions that are sensitive to LIS1 dosage, thus promoting our understanding of
      the role of LIS1 in the developing cortex.

PMID- 11344261
TI  - Precision in mouse behavior genetics.

PMID- 11344262
TI  - Cerebral energetics and the glycogen shunt: neurochemical basis of functional
      imaging.
AB  - Positron-emission tomography and functional MRS imaging signals can be analyzed
      to derive neurophysiological values of cerebral blood flow or volume and cerebral
      metabolic consumption rates of glucose (CMR(Glc)) or oxygen (CMR(O(2))). Under
      basal physiological conditions in the adult mammalian brain, glucose oxidation is
      nearly complete so that the oxygen-to-glucose index (OGI), given by the ratio of
      CMR(O(2))/CMR(Glc), is close to the stoichiometric value of 6. However, a survey
      of functional imaging data suggests that the OGI is activity dependent, moving
      further below the oxidative value of 6 as activity is increased. Brain lactate
      concentrations also increase with stimulation. These results had led to the
      concept that brain activation is supported by anaerobic glucose metabolism, which
      was inconsistent with basal glucose oxidation. These differences are resolved
      here by a proposed model of glucose energetics, in which a fraction of glucose is
      cycled through the cerebral glycogen pool, a fraction that increases with degree
      of brain activation. The "glycogen shunt," although energetically less efficient
      than glycolysis, is followed because of its ability to supply glial energy in
      milliseconds for rapid neurotransmitter clearance, as a consequence of which OGI
      is lowered and lactate is increased. The value of OGI observed is consistent with
      passive lactate efflux, driven by the observed lactate concentration, for the few
      experiments with complete data. Although the OGI changes during activation, the
      energies required per neurotransmitter release (neuronal) and clearance (glial)
      are constant over a wide range of brain activity.

PMID- 11344263
TI  - Diffractive optics-based heterodyne-detected four-wave mixing signals of protein
      motion: from "protein quakes" to ligand escape for myoglobin.
AB  - Ligand transport through myoglobin (Mb) has been observed by using optically
      heterodyne-detected transient grating spectroscopy. Experimental implementation
      using diffractive optics has provided unprecedented sensitivity for the study of
      protein motions by enabling the passive phase locking of the four beams that
      constitute the experiment, and an unambiguous separation of the Real and
      Imaginary parts of the signal. Ligand photodissociation of carboxymyoglobin
      (MbCO) induces a sequence of events involving the relaxation of the protein
      structure to accommodate ligand escape. These motions show up in the Real part of
      the signal. The ligand (CO) transport process involves an initial, small
      amplitude, change in volume, reflecting the transit time of the ligand through
      the protein, followed by a significantly larger volume change with ligand escape
      to the surrounding water. The latter process is well described by a single
      exponential process of 725 +/- 15 ns. at room temperature. The overall dynamics
      provide a distinctive signature that can be understood in the context of
      segmental protein fluctuations that aid ligand escape via a few specific
      cavities, and they suggest the existence of discrete escape pathways.

PMID- 11344264
TI  - Nerve growth factor displays stimulatory effects on human skin and lung
      fibroblasts, demonstrating a direct role for this factor in tissue repair.
AB  - Nerve growth factor (NGF) is a polypeptide which, in addition to its effect on
      nerve cells, is believed to play a role in inflammatory responses and in tissue
      repair. Because fibroblasts represent the main target and effector cells in these
      processes, to investigate whether NGF is involved in lung and skin tissue repair,
      we studied the effect of NGF on fibroblast migration, proliferation, collagen
      metabolism, modulation into myofibroblasts, and contraction of collagen gel. Both
      skin and lung fibroblasts were found to produce NGF and to express tyrosine
      kinase receptor (trkA) under basal conditions, whereas the low-affinity p75
      receptor was expressed only after prolonged NGF exposure. NGF significantly
      induced skin and lung fibroblast migration in an in vitro model of wounded
      fibroblast and skin migration in Boyden chambers. Nevertheless NGF did not
      influence either skin or lung fibroblast proliferation, collagen production, or
      metalloproteinase production or activation. In contrast, culture of both lung and
      skin fibroblasts with NGF modulated their phenotype into myofibroblasts.
      Moreover, addition of NGF to both fibroblast types embedded in collagen gel
      increased their contraction. Fibrotic human lung or skin tissues displayed
      immunoreactivity for NGF, trkA, and p75. These data show a direct pro-fibrogenic
      effect of NGF on skin and lung fibroblasts and therefore indicate a role for NGF
      in tissue repair and fibrosis.

PMID- 11344265
TI  - Measuring the diaspora for virus-specific CD8+ T cells.
AB  - The CD8(+) T cell diaspora has been analyzed after secondary challenge with an
      influenza A virus that replicates only in the respiratory tract. Numbers of
      D(b)NP(366)- and D(b)PA(224)-specific CD8(+) T cells were measured by tetramer
      staining at the end of the recall response, then followed sequentially in the
      lung, lymph nodes, spleen, blood, and other organs. The extent of clonal
      expansion did not reflect the sizes of the preexisting memory T cell pools.
      Although the high-frequency CD8(+) tetramer(+) populations in the pneumonic lung
      and mediastinal lymph nodes fell rapidly from peak values, the "whole mouse"
      virus-specific CD8(+) T cell counts decreased only 2-fold over the 4 weeks after
      infection, then subsided at a fairly steady rate to reach a plateau at about 2
      months. The largest numbers were found throughout in the spleen, then the bone
      marrow. The CD8(+)D(b)NP(366)+ and CD8(+)D(b)PA(224)+ sets remained significantly
      enlarged for at least 4 months, declining at equivalent rates while retaining the
      nucleoprotein > acid polymerase immunodominance hierarchy characteristic of the
      earlier antigen-driven phase. Lowest levels of the CD69 "activation marker" were
      detected consistently on virus-specific CD8(+) T cells in the blood, then the
      spleen. Those in the bone marrow and liver were intermediate, and CD69(hi) T
      cells were very prominent in the regional lymph nodes and the nasal-associated
      lymphoid tissue. Any population of "resting" CD8(+) memory T cells is thus
      phenotypically heterogeneous, widely dispersed, and subject to broad homeostatic
      and local environmental effects irrespective of epitope specificity or magnitude.

PMID- 11344266
TI  - Mutant G protein alpha subunit activated by Gbeta gamma: a model for receptor
      activation?
AB  - How receptors catalyze exchange of GTP for GDP bound to the Galpha subunit of
      trimeric G proteins is not known. One proposal is that the receptor uses the G
      protein's betagamma heterodimer as a lever, tilting it to pull open the guanine
      nucleotide binding pocket of Galpha. To test this possibility, we designed a
      mutant Galpha that would bind to betagamma in the tilted conformation. To do so,
      we excised a helical turn (four residues) from the N-terminal region of alpha(s),
      the alpha subunit of G(S), the stimulatory regulator of adenylyl cyclase. In the
      presence, but not in the absence, of transiently expressed beta(1) and gamma(2),
      this mutant (alpha(s)Delta), markedly stimulated cAMP accumulation. This effect
      depended on the ability of the coexpressed beta protein to interact normally with
      the lip of the nucleotide binding pocket of alpha(s)Delta. We substituted alanine
      for an aspartate in beta(1) that binds to a lysine (K206) in the lip of the alpha
      subunit's nucleotide binding pocket. Coexpressed with alpha(s)Delta and gamma(2),
      this mutant, beta(1)-D228A, elevated cAMP much less than did beta(1)-wild type;
      it did bind to alpha(s)Delta normally, however, as indicated by its unimpaired
      ability to target alpha(s)Delta to the plasma membrane. We conclude that
      betagamma can activate alpha(s) and that this effect probably involves both a
      tilt of betagamma relative to alpha(s) and interaction of beta with the lip of
      the nucleotide binding pocket. We speculate that receptors use a similar
      mechanism to activate trimeric G proteins.

PMID- 11344267
TI  - Altered stability of pulmonary surfactant in SP-C-deficient mice.
AB  - The surfactant protein C (SP-C) gene encodes an extremely hydrophobic, 4-kDa
      peptide produced by alveolar epithelial cells in the lung. To discern the role of
      SP-C in lung function, SP-C-deficient (-/-) mice were produced. The SP-C (-/-)
      mice were viable at birth and grew normally to adulthood without apparent
      pulmonary abnormalities. SP-C mRNA was not detected in the lungs of SP-C (-/-)
      mice, nor was mature SP-C protein detected by Western blot of alveolar lavage
      from SP-C (-/-) mice. The levels of the other surfactant proteins (A, B, D) in
      alveolar lavage were comparable to those in wild-type mice. Surfactant pool
      sizes, surfactant synthesis, and lung morphology were similar in SP-C (-/-) and
      SP-C (+/+) mice. Lamellar bodies were present in SP-C (-/-) type II cells, and
      tubular myelin was present in the alveolar lumen. Lung mechanics studies
      demonstrated abnormalities in lung hysteresivity (a term used to reflect the
      mechanical coupling between energy dissipative forces and tissue-elastic
      properties) at low, positive-end, expiratory pressures. The stability of captive
      bubbles with surfactant from the SP-C (-/-) mice was decreased significantly,
      indicating that SP-C plays a role in the stabilization of surfactant at low lung
      volumes, a condition that may accompany respiratory distress syndrome in infants
      and adults.

PMID- 11344268
TI  - Large vortex-like structure of dipole field in computer models of liquid water
      and dipole-bridge between biomolecules.
AB  - We propose a framework to describe the cooperative orientational motions of water
      molecules in liquid water and around solute molecules in water solutions. From
      molecular dynamics (MD) simulation a new quantity "site-dipole field" is defined
      as the averaged orientation of water molecules that pass through each spatial
      position. In the site-dipole field of bulk water we found large vortex-like
      structures of more than 10 A in size. Such coherent patterns persist more than
      300 ps although the orientational memory of individual molecules is quickly lost.
      A 1-ns MD simulation of systems consisting of two amino acids shows that the
      fluctuations of site-dipole field of solvent are pinned around the amino acids,
      resulting in a stable dipole-bridge between side-chains of amino acids. The
      dipole-bridge is significantly formed even for the side-chain separation of 14 A,
      which corresponds to five layers of water. The way that dipole-bridge forms
      sensitively depends on the side-chain orientations and thereby explains the
      specificity in the solvent-mediated interactions between biomolecules.

PMID- 11344269
TI  - Cloning and characterization of FGF23 as a causative factor of tumor-induced
      osteomalacia.
AB  - Tumor-induced osteomalacia (TIO) is one of the paraneoplastic diseases
      characterized by hypophosphatemia caused by renal phosphate wasting. Because
      removal of responsible tumors normalizes phosphate metabolism, an unidentified
      humoral phosphaturic factor is believed to be responsible for this syndrome. To
      identify the causative factor of TIO, we obtained cDNA clones that were
      abundantly expressed only in a tumor causing TIO and constructed tumor-specific
      cDNA contigs. Based on the sequence of one major contig, we cloned 2,270-bp cDNA,
      which turned out to encode fibroblast growth factor 23 (FGF23). Administration of
      recombinant FGF23 decreased serum phosphate in mice within 12 h. When Chinese
      hamster ovary cells stably expressing FGF23 were s.c. implanted into nude mice,
      hypophosphatemia with increased renal phosphate clearance was observed. In
      addition, a high level of serum alkaline phosphatase, low 1,25-dihydroxyvitamin
      D, deformity of bone, and impairment of body weight gain became evident.
      Histological examination showed marked increase of osteoid and widening of growth
      plate. Thus, continuous production of FGF23 reproduced clinical, biochemical, and
      histological features of TIO in vivo. Analyses for recombinant FGF23 products
      produced by Chinese hamster ovary cells indicated proteolytic cleavage of FGF23
      at the RXXR motif. Recent genetic study indicates that missense mutations in this
      RXXR motif of FGF23 are responsible for autosomal dominant hypophosphatemic
      rickets, another hypophosphatemic disease with similar features to TIO. We
      conclude that overproduction of FGF23 causes TIO, whereas mutations in the FGF23
      gene result in autosomal dominant hypophosphatemic rickets possibly by preventing
      proteolytic cleavage and enhancing biological activity of FGF23.

PMID- 11344270
TI  - Evidence in support of a four transmembrane-pore-transmembrane topology model for
      the Arabidopsis thaliana Na+/K+ translocating AtHKT1 protein, a member of the
      superfamily of K+ transporters.
AB  - The Arabidopsis thaliana AtHKT1 protein, a Na(+)/K(+) transporter, is capable of
      mediating inward Na(+) currents in Xenopus laevis oocytes and K(+) uptake in
      Escherichia coli. HKT1 proteins are members of a superfamily of K(+)
      transporters. These proteins have been proposed to contain eight transmembrane
      segments and four pore-forming regions arranged in a mode similar to that of a
      K(+) channel tetramer. However, computer analysis of the AtHKT1 sequence
      identified eleven potential transmembrane segments. We have investigated the
      membrane topology of AtHKT1 with three different techniques. First, a gene fusion
      alkaline phosphatase study in E. coli clearly defined the topology of the N
      terminal and middle region of AtHKT1, but the model for membrane folding of the C
      terminal region had to be refined. Second, with a reticulocyte-lysate
      supplemented with dog-pancreas microsomes, we demonstrated that N-glycosylation
      occurs at position 429 of AtHKT1. An engineered unglycosylated protein variant,
      N429Q, mediated Na(+) currents in X. laevis oocytes with the same characteristics
      as the wild-type protein, indicating that N-glycosylation is not essential for
      the functional expression and membrane targeting of AtHKT1. Five potential
      glycosylation sites were introduced into the N429Q. Their pattern of
      glycosylation supported the model based on the E. coli-alkaline phosphatase data.
      Third, immunocytochemical experiments with FLAG-tagged AtHKT1 in HEK293 cells
      revealed that the N and C termini of AtHKT1, and the regions containing residues
      135-142 and 377-384, face the cytosol, whereas the region of residues 55-62 is
      exposed to the outside. Taken together, our results show that AtHKT1 contains
      eight transmembrane-spanning segments.

PMID- 11344271
TI  - Leptin induces vascular permeability and synergistically stimulates angiogenesis
      with FGF-2 and VEGF.
AB  - Most endocrine hormones are produced in tissues and organs with permeable
      microvessels that may provide an excess of hormones to be transported by the
      blood circulation to the distal target organ. Here, we investigate whether
      leptin, an endocrine hormone, induces the formation of vascular fenestrations and
      permeability, and we characterize its angiogenic property in the presence of
      other angiogenic factors. We provide evidence that leptin-induced new blood
      vessels are fenestrated. Under physiological conditions, capillary fenestrations
      are found in the leptin-producing adipose tissue in lean mice. In contrast, no
      vascular fenestrations were detected in the adipose tissue of leptin-deficient
      ob/ob mice. Thus, leptin plays a critical role in the maintenance and regulation
      of vascular fenestrations in the adipose tissue. Leptin induces a rapid vascular
      permeability response when administrated intradermally. Further, leptin
      synergistically stimulates angiogenesis with fibroblast growth factor (FGF)-2 and
      vascular endothelial growth factor (VEGF), the two most potent and commonly
      expressed angiogenic factors. These findings demonstrate that leptin has another
      new function-the increase of vascular permeability.

PMID- 11344272
TI  - Drosophila phosphoinositide-dependent kinase-1 regulates apoptosis and growth via
      the phosphoinositide 3-kinase-dependent signaling pathway.
AB  - Phosphoinositide-dependent kinase-1 (PDK-1) is a central mediator of the cell
      signaling between phosphoinositide 3-kinase (PI3K) and various intracellular
      serine/threonine kinases including Akt/protein kinase B (PKB), p70 S6 kinases,
      and protein kinase C. Recent studies with cell transfection experiments have
      implied that PDK-1 may be involved in various cell functions including cell
      growth and apoptosis. However, despite its pivotal role in cellular signalings,
      the in vivo functions of PDK-1 in a multicellular system have rarely been
      investigated. Here, we have isolated Drosophila PDK-1 (dPDK-1) mutants and
      characterized the in vivo roles of the kinase. Drosophila deficient in the dPDK-1
      gene exhibited lethality and an apoptotic phenotype in the embryonic stage.
      Conversely, overexpression of dPDK-1 increased cell and organ size in a
      Drosophila PI3K-dependent manner. dPDK-1 not only could activate Drosophila
      Akt/PKB (Dakt1), but also substitute the in vivo functions of its mammalian
      ortholog to activate Akt/PKB. This functional interaction between dPDK-1 and
      Dakt1 was further confirmed through genetic analyses in Drosophila. On the other
      hand, cAMP-dependent protein kinase, which has been proposed as a possible target
      of dPDK-1, did not interact with dPDK-1. In conclusion, our findings provide
      direct evidence that dPDK-1 regulates cell growth and apoptosis during Drosophila
      development via the PI3K-dependent signaling pathway and demonstrate our
      Drosophila system to be a powerful tool for elucidating the in vivo functions and
      targets of PDK-1.

PMID- 11344273
TI  - Pro-apoptotic gene expression mediated by the p38 mitogen-activated protein
      kinase signal transduction pathway.
AB  - Neurotrophic factor deprivation causes apoptosis by a mechanism that requires
      macromolecular synthesis. This fact suggests that gene expression is necessary to
      achieve cell death. To identify mRNA that is expressed in apoptotic cells we used
      subtractive hybridization with cDNA prepared from neuronal pheochromocytoma
      cells. Monoamine oxidase (MAO) expression was increased in cells during nerve
      growth factor withdrawal-induced apoptosis. The increased apoptosis and induction
      of MAO was prevented by inhibition of the p38 mitogen-activated protein (MAP)
      kinase pathway. MAO may contribute to the apoptotic process because inhibition of
      MAO activity suppressed cell death. Together, these data indicate that MAO may be
      a target of pro-apoptotic signal transduction by the p38 MAP kinase pathway.

PMID- 11344275
TI  - Changes in the prevalence of chronic disability in the United States black and
      nonblack population above age 65 from 1982 to 1999.
AB  - Survey evidence through the early 1990s generally suggests a reduction in
      disability in the elderly population of the United States. Because the evidence
      is not fully consistent, several authors have speculated about whether disability
      declines will continue. This paper reports results from the 1999 National Long
      Term Care Survey on disability trends from 1982 through 1999. It is found that
      disability continued to decline in the 1994 to 1999 period, and that the decline
      was greater in the 1990s than in the 1980s. The disability decline from 1982 to
      1989 was 0.26% per year, from 1989 to 1994 it was 0.38% per year, and from 1994
      to 1999 it was 0.56% per year. In addition, disability declined by a greater
      percentage for blacks than for nonblacks over the 1989 to 1999 period.

PMID- 11344276
TI  - A fluid connection: cholesterol and Abeta.

PMID- 11344274
TI  - Antiviral activities of the soluble extracellular domains of type I interferon
      receptors.
AB  - Alternative splicing leads to the expression of multiple isoforms of the subunits
      (IFNAR1 and IFNAR2) of the type I IFN receptor. Here we describe two transcripts
      representing extracellular forms of ovine IFNAR1 and show that soluble
      extracellular forms of both IFNAR2 and IFNAR1, prepared in recombinant form in
      Escherichia coli, have antiviral (AV) activity in the absence of IFN. Exposure of
      Madin-Darby bovine kidney cells to the extracellular domain (R2E) of IFNAR2 at
      concentrations as low as 10 nM afforded complete protection against vesicular
      stomatitis virus and led to the rapid activation of the transcription factors
      ISGF3 and GAF. Although R2E can bind IFN (K(d) approximately 70 nM), activity was
      observed irrespective of whether or not ligand was present. R2E was inactive on
      mouse L929 cells but active on L929 cells expressing a membraneanchored,
      ovine/human chimeric IFNAR2 with an ovine extracellular domain. The data suggest
      that AV activity is conferred by the ability of soluble R2E to associate with the
      transfected IFNAR2 subunit rather than resident murine IFNAR1. Soluble
      extracellular forms of IFNAR1 have lower AV activity than R2E on Madin-Darby
      bovine kidney cells but are less species-specific and protect wild-type L929
      cells as efficiently as the transfected cell line, presumably by interacting with
      one of the murine receptor subunits.

PMID- 11344277
TI  - Neocentromeres and human artificial chromosomes: an unnatural act.

PMID- 11344278
TI  - Notch signaling during vascular development.

PMID- 11344279
TI  - Don't stop for repairs in a war zone: Darwinian evolution unites genes and
      environment in cancer development.

PMID- 11344280
TI  - Livestock genetic origins: goats buck the trend.

PMID- 11344281
TI  - When developmental biology meets human pathology.

PMID- 11344283
TI  - The biotic crisis and the future of evolution.
AB  - The biotic crisis overtaking our planet is likely to precipitate a major
      extinction of species. That much is well known. Not so well known but probably
      more significant in the long term is that the crisis will surely disrupt and
      deplete certain basic processes of evolution, with consequences likely to persist
      for millions of years. Distinctive features of future evolution could include a
      homogenization of biotas, a proliferation of opportunistic species, a pest-and
      weed ecology, an outburst of speciation among taxa that prosper in human
      dominated ecosystems, a decline of biodisparity, an end to the speciation of
      large vertebrates, the depletion of "evolutionary powerhouses" in the tropics,
      and unpredictable emergent novelties. Despite this likelihood, we have only a
      rudimentary understanding of how we are altering the evolutionary future. As a
      result of our ignorance, conservation policies fail to reflect long-term
      evolutionary aspects of biodiversity loss.

PMID- 11344284
TI  - Lessons from the past: evolutionary impacts of mass extinctions.
AB  - Mass extinctions have played many evolutionary roles, involving differential
      survivorship or selectivity of taxa and traits, the disruption or preservation of
      evolutionary trends and ecosystem organization, and the promotion of taxonomic
      and morphological diversifications-often along unexpected trajectories-after the
      destruction or marginalization of once-dominant clades. The fossil record
      suggests that survivorship during mass extinctions is not strictly random, but it
      often fails to coincide with factors promoting survival during times of low
      extinction intensity. Although of very serious concern, present-day extinctions
      have not yet achieved the intensities seen in the Big Five mass extinctions of
      the geologic past, which each removed > or =50% of the subset of relatively
      abundant marine invertebrate genera. The best comparisons for predictive purposes
      therefore will involve factors such as differential extinction intensities among
      regions, clades, and functional groups, rules governing postextinction biotic
      interchanges and evolutionary dynamics, and analyses of the factors that cause
      taxa and evolutionary trends to continue unabated, to suffer setbacks but resume
      along the same trajectory, to survive only to fall into a marginal role or
      disappear ("dead clade walking"), or to undergo a burst of diversification. These
      issues need to be addressed in a spatially explicit framework, because the fossil
      record suggests regional differences in postextinction diversification dynamics
      and biotic interchanges. Postextinction diversifications lag far behind the
      initial taxonomic and morphological impoverishment and homogenization; they do
      not simply reoccupy vacated adaptive peaks, but explore opportunities as opened
      and constrained by intrinsic biotic factors and the ecological and evolutionary
      context of the radiation.

PMID- 11344285
TI  - Lessons from the past: biotic recoveries from mass extinctions.
AB  - Although mass extinctions probably account for the disappearance of less than 5%
      of all extinct species, the evolutionary opportunities they have created have had
      a disproportionate effect on the history of life. Theoretical considerations and
      simulations have suggested that the empty niches created by a mass extinction
      should refill rapidly after extinction ameliorates. Under logistic models, this
      biotic rebound should be exponential, slowing as the environmental carrying
      capacity is approached. Empirical studies reveal a more complex dynamic,
      including positive feedback and an exponential growth phase during recoveries.
      Far from a model of refilling ecospace, mass extinctions appear to cause a
      collapse of ecospace, which must be rebuilt during recovery. Other generalities
      include the absence of a clear correlation between the magnitude of extinction
      and the pace of recovery or the resulting ecological and evolutionary disruption
      the presence of a survival interval, with few originations, immediately after an
      extinction and preceding the recovery phase, and the presence of many lineages
      that persist through an extinction event only to disappear during the subsequent
      recovery. Several recoveries include numerous missing lineages, groups that are
      found before the extinction, then latter in the recovery, but are missing during
      the initial survival-recovery phase. The limited biogeographic studies of
      recoveries suggest considerable variability between regions.

PMID- 11344286
TI  - Loss of speciation rate will impoverish future diversity.
AB  - Human activities have greatly reduced the amount of the earth's area available to
      wild species. As the area they have left declines, so will their rates of
      speciation. This loss of speciation will occur for two reasons: species with
      larger geographical ranges speciate faster; and loss of area drives up extinction
      rates, thus reducing the number of species available for speciation. Theory
      predicts steady states in species diversity, and fossils suggest that these have
      typified life for most of the past 500 million years. Modern and fossil evidence
      indicates that, at the scale of the whole earth and its major biogeographical
      provinces, those steady states respond linearly, or nearly so, to available area.
      Hence, a loss of x% of area will produce a loss of about x% of species. Local
      samples of habitats merely echo the diversity available in the whole province of
      which they are a part. So, conservation tactics that rely on remnant patches to
      preserve diversity cannot succeed for long. Instead, diversity will decay to a
      depauperate steady state in two phases. The first will involve deterministic
      extinctions, reflecting the loss of all areas in which a species can ordinarily
      sustain its demographics. The second will be stochastic, reflecting accidents
      brought on by global warming, new diseases, and commingling the species of the
      separate bio-provinces. A new kind of conservation effort, reconciliation
      ecology, can avoid this decay. Reconciliation ecology discovers how to modify and
      diversify anthropogenic habitats so that they harbor a wide variety of species.
      It develops management techniques that allow humans to share their geographical
      range with wild species.

PMID- 11344287
TI  - What was natural in the coastal oceans?
AB  - Humans transformed Western Atlantic coastal marine ecosystems before modern
      ecological investigations began. Paleoecological, archeological, and historical
      reconstructions demonstrate incredible losses of large vertebrates and oysters
      from the entire Atlantic coast. Untold millions of large fishes, sharks, sea
      turtles, and manatees were removed from the Caribbean in the 17th to 19th
      centuries. Recent collapses of reef corals and seagrasses are due ultimately to
      losses of these large consumers as much as to more recent changes in climate,
      eutrophication, or outbreaks of disease. Overfishing in the 19th century reduced
      vast beds of oysters in Chesapeake Bay and other estuaries to a few percent of
      pristine abundances and promoted eutrophication. Mechanized harvesting of bottom
      fishes like cod set off a series of trophic cascades that eliminated kelp forests
      and then brought them back again as fishers fished their way down food webs to
      small invertebrates. Lastly, but most pervasively, mechanized harvesting of the
      entire continental shelf decimated large, long-lived fishes and destroyed three
      dimensional habitats built up by sessile corals, bryozoans, and sponges. The
      universal pattern of losses demonstrates that no coastal ecosystem is pristine
      and few wild fisheries are sustainable along the entire Western Atlantic coast.
      Reconstructions of ecosystems lost only a century or two ago demonstrate
      attainable goals of establishing large and effective marine reserves if society
      is willing to pay the costs. Historical reconstructions provide a new scientific
      framework for manipulative experiments at the ecosystem scale to explore the
      feasibility and benefits of protection of our living coastal resources.

PMID- 11344288
TI  - The future of coral reefs.
AB  - Coral reefs, with their millions of species, have changed profoundly because of
      the effects of people, and will continue to do so for the foreseeable future.
      Reefs are subject to many of the same processes that affect other human-dominated
      ecosystems, but some special features merit emphasis: (i) Many dominant reef
      builders spawn eggs and sperm into the water column, where fertilization occurs.
      They are thus particularly vulnerable to Allee effects, including potential
      extinction associated with chronic reproductive failure. (ii) The corals likely
      to be most resistant to the effects of habitat degradation are small, short-lived
      "weedy" corals that have limited dispersal capabilities at the larval stage.
      Habitat degradation, together with habitat fragmentation, will therefore lead to
      the establishment of genetically isolated clusters of inbreeding corals. (iii)
      Increases in average sea temperatures by as little as 1 degrees C, a likely
      result of global climate change, can cause coral "bleaching" (the breakdown of
      coral-algal symbiosis), changes in symbiont communities, and coral death. (iv)
      The activities of people near reefs increase both fishing pressure and nutrient
      inputs. In general, these processes favor more rapidly growing competitors, often
      fleshy seaweeds, and may also result in explosions of predator populations. (v)
      Combinations of stress appear to be associated with threshold responses and
      ecological surprises, including devastating pathogen outbreaks. (vi) The fossil
      record suggests that corals as a group are more likely to suffer extinctions than
      some of the groups that associate with them, whose habitat requirements may be
      less stringent.

PMID- 11344289
TI  - Disrupting evolutionary processes: the effect of habitat fragmentation on
      collared lizards in the Missouri Ozarks.
AB  - Humans affect biodiversity at the genetic, species, community, and ecosystem
      levels. This impact on genetic diversity is critical, because genetic diversity
      is the raw material of evolutionary change, including adaptation and speciation.
      Two forces affecting genetic variation are genetic drift (which decreases genetic
      variation within but increases genetic differentiation among local populations)
      and gene flow (which increases variation within but decreases differentiation
      among local populations). Humans activities often augment drift and diminish gene
      flow for many species, which reduces genetic variation in local populations and
      prevents the spread of adaptive complexes outside their population of origin,
      thereby disrupting adaptive processes both locally and globally within a species.
      These impacts are illustrated with collared lizards (Crotaphytus collaris) in the
      Missouri Ozarks. Forest fire suppression has reduced habitat and disrupted gene
      flow in this lizard, thereby altering the balance toward drift and away from gene
      flow. This balance can be restored by managed landscape burns. Some have argued
      that, although human-induced fragmentation disrupts adaptation, it will also
      ultimately produce new species through founder effects. However, population
      genetic theory and experiments predict that most fragmentation events caused by
      human activities will facilitate not speciation, but local extinction. Founder
      events have played an important role in the macroevolution of certain groups, but
      only when ecological opportunities are expanding rather than contracting. The
      general impact of human activities on genetic diversity disrupts or diminishes
      the capacity for adaptation, speciation, and macroevolutionary change. This
      impact will ultimately diminish biodiversity at all levels.

PMID- 11344290
TI  - Human-caused environmental change: impacts on plant diversity and evolution.
AB  - Human-caused environmental changes are creating regional combinations of
      environmental conditions that, within the next 50 to 100 years, may fall outside
      the envelope within which many of the terrestrial plants of a region evolved.
      These environmental modifications might become a greater cause of global species
      extinction than direct habitat destruction. The environmental constraints
      undergoing human modification include levels of soil nitrogen, phosphorus,
      calcium and pH, atmospheric CO(2), herbivore, pathogen, and predator densities,
      disturbance regimes, and climate. Extinction would occur because the
      physiologies, morphologies, and life histories of plants limit each species to
      being a superior competitor for a particular combination of environmental
      constraints. Changes in these constraints would favor a few species that would
      competitively displace many other species from a region. In the long-term, the
      "weedy" taxa that became the dominants of the novel conditions imposed by global
      change should become the progenitors of a series of new species that are
      progressively less weedy and better adapted to the new conditions. The relative
      importance of evolutionary versus community ecology responses to global
      environmental change would depend on the extent of regional and local recruitment
      limitation, and on whether the suite of human-imposed constraints were novel just
      regionally or on continental or global scales.

PMID- 11344291
TI  - Plant biology in the future.
AB  - In the beginning of modern plant biology, plant biologists followed a simple
      model for their science. This model included important branches of plant biology
      known then. Of course, plants had to be identified and classified first. Thus,
      there was much work on taxonomy, genetics, and physiology. Ecology and evolution
      were approached implicitly, rather than explicitly, through paleobotany,
      taxonomy, morphology, and historical geography. However, the burgeoning explosion
      of knowledge and great advances in molecular biology, e.g., to the extent that
      genes for specific traits can be added (or deleted) at will, have created a
      revolution in the study of plants. Genomics in agriculture has made it possible
      to address many important issues in crop production by the identification and
      manipulation of genes in crop plants. The current model of plant study differs
      from the previous one in that it places greater emphasis on developmental
      controls and on evolution by differential fitness. In a rapidly changing
      environment, the current model also explicitly considers the phenotypic variation
      among individuals on which selection operates. These are calls for the unity of
      science. In fact, the proponents of "Complexity Theory" think there are common
      algorithms describing all levels of organization, from atoms all the way to the
      structure of the universe, and that when these are discovered, the issue of
      scaling will be greatly simplified! Plant biology must seriously contribute to,
      among other things, meeting the nutritional needs of the human population. This
      challenge constitutes a key part of the backdrop against which future evolution
      will occur. Genetic engineering technologies are and will continue to be an
      important component of agriculture; however, we must consider the evolutionary
      implications of these new technologies. Meeting these demands requires drastic
      changes in the undergraduate curriculum. Students of biology should be trained in
      molecular, cellular, organismal, and ecosystem biology, including all living
      organisms.

PMID- 11344292
TI  - The evolutionary impact of invasive species.
AB  - Since the Age of Exploration began, there has been a drastic breaching of
      biogeographic barriers that previously had isolated the continental biotas for
      millions of years. We explore the nature of these recent biotic exchanges and
      their consequences on evolutionary processes. The direct evidence of evolutionary
      consequences of the biotic rearrangements is of variable quality, but the results
      of trajectories are becoming clear as the number of studies increases. There are
      examples of invasive species altering the evolutionary pathway of native species
      by competitive exclusion, niche displacement, hybridization, introgression,
      predation, and ultimately extinction. Invaders themselves evolve in response to
      their interactions with natives, as well as in response to the new abiotic
      environment. Flexibility in behavior, and mutualistic interactions, can aid in
      the success of invaders in their new environment.

PMID- 11344293
TI  - Rapid plant diversification: planning for an evolutionary future.
AB  - Systematic conservation planning is a branch of conservation biology that seeks
      to identify spatially explicit options for the preservation of biodiversity.
      Alternative systems of conservation areas are predictions about effective ways of
      promoting the persistence of biodiversity; therefore, they should consider not
      only biodiversity pattern but also the ecological and evolutionary processes that
      maintain and generate species. Most research and application, however, has
      focused on pattern representation only. This paper outlines the development of a
      conservation system designed to preserve biodiversity pattern and process in the
      context of a rapidly changing environment. The study area is the Cape Floristic
      Region (CFR), a biodiversity hotspot of global significance, located in
      southwestern Africa. This region has experienced rapid (post-Pliocene) ecological
      diversification of many plant lineages; there are numerous genera with large
      clusters of closely related species (flocks) that have subdivided habitats at a
      very fine scale. The challenge is to design conservation systems that will
      preserve both the pattern of large numbers of species and various natural
      processes, including the potential for lineage turnover. We outline an approach
      for designing a system of conservation areas to incorporate the spatial
      components of the evolutionary processes that maintain and generate biodiversity
      in the CFR. We discuss the difficulty of assessing the requirements for pattern
      versus process representation in the face of ongoing threats to biodiversity, the
      difficulty of testing the predictions of alternative conservation systems, and
      the widespread need in conservation planning to incorporate and set targets for
      the spatial components (or surrogates) of processes.

PMID- 11344294
TI  - Human-modified ecosystems and future evolution.
AB  - Our global impact is finally receiving the scientific attention it deserves. The
      outcome will largely determine the future course of evolution. Human-modified
      ecosystems are shaped by our activities and their side effects. They share a
      common set of traits including simplified food webs, landscape homogenization,
      and high nutrient and energy inputs. Ecosystem simplification is the ecological
      hallmark of humanity and the reason for our evolutionary success. However, the
      side effects of our profligacy and poor resource practices are now so pervasive
      as to threaten our future no less than that of biological diversity itself. This
      article looks at human impact on ecosystems and the consequences for evolution.
      It concludes that future evolution will be shaped by our awareness of the global
      threats, our willingness to take action, and our ability to do so. Our ability is
      presently hampered by several factors, including the poor state of ecosystem and
      planetary knowledge, ignorance of human impact, lack of guidelines for
      sustainability, and a paucity of good policies, practices, and incentives for
      adopting those guidelines in daily life. Conservation philosophy, science, and
      practice must be framed against the reality of human-dominated ecosystems, rather
      than the separation of humanity and nature underlying the modern conservation
      movement. The steps scientists can take to imbed science in conservation and
      conservation in the societal process affecting the future of ecosystems and human
      well-being are discussed.

PMID- 11344295
TI  - The current biodiversity extinction event: scenarios for mitigation and recovery.
AB  - The current massive degradation of habitat and extinction of species is taking
      place on a catastrophically short timescale, and their effects will fundamentally
      reset the future evolution of the planet's biota. The fossil record suggests that
      recovery of global ecosystems has required millions or even tens of millions of
      years. Thus, intervention by humans, the very agents of the current environmental
      crisis, is required for any possibility of short-term recovery or maintenance of
      the biota. Many current recovery efforts have deficiencies, including
      insufficient information on the diversity and distribution of species, ecological
      processes, and magnitude and interaction of threats to biodiversity (pollution,
      overharvesting, climate change, disruption of biogeochemical cycles, introduced
      or invasive species, habitat loss and fragmentation through land use, disruption
      of community structure in habitats, and others). A much greater and more urgently
      applied investment to address these deficiencies is obviously warranted.
      Conservation and restoration in human-dominated ecosystems must strengthen
      connections between human activities, such as agricultural or harvesting
      practices, and relevant research generated in the biological, earth, and
      atmospheric sciences. Certain threats to biodiversity require intensive
      international cooperation and input from the scientific community to mitigate
      their harmful effects, including climate change and alteration of global
      biogeochemical cycles. In a world already transformed by human activity, the
      connection between humans and the ecosystems they depend on must frame any
      strategy for the recovery of the biota.

PMID- 11344296
TI  - Declines of biomes and biotas and the future of evolution.
AB  - Although panel discussants disagreed whether the biodiversity crisis constitutes
      a mass extinction event, all agreed that current extinction rates are 50-500
      times background and are increasing and that the consequences for the future
      evolution of life are serious. In response to the on-going rapid decline of
      biomes and homogenization of biotas, the panelists predicted changes in species
      geographic ranges, genetic risks of extinction, genetic assimilation, natural
      selection, mutation rates, the shortening of food chains, the increase in
      nutrient-enriched niches permitting the ascendancy of microbes, and the
      differential survival of ecological generalists. Rates of evolutionary processes
      will change in different groups, and speciation in the larger vertebrates is
      essentially over. Action taken over the next few decades will determine how
      impoverished the biosphere will be in 1,000 years when many species will suffer
      reduced evolvability and require interventionist genetic and ecological
      management. Whether the biota will continue to provide the dependable ecological
      services humans take for granted is less clear. The discussants offered
      recommendations, including two of paramount importance (concerning human
      populations and education), seven identifying specific scientific activities to
      better equip us for stewardship of the processes of evolution, and one suggesting
      that such stewardship is now our responsibility. The ultimate test of
      evolutionary biology as a science is not whether it solves the riddles of the
      past but rather whether it enables us to manage the future of the biosphere. Our
      inability to make clearer predictions about the future of evolution has serious
      consequences for both biodiversity and humanity.

PMID- 11344297
TI  - Intervening in evolution: ethics and actions.
AB  - Biologists should help to guide a process of cultural evolution in which society
      determines how much effort, if any, is ethically required to preserve options in
      biological evolution. Evolutionists, conservation biologists, and ecologists
      should be doing more research to determine actions that would best help to avoid
      foreclosing evolutionary options.

PMID- 11344298
TI  - Crystal structures of the vitamin D receptor complexed to superagonist 20-epi
      ligands.
AB  - The crystal structures of the ligand-binding domain (LBD) of the vitamin D
      receptor complexed to 1alpha,25(OH)(2)D(3) and the 20-epi analogs, MC1288 and
      KH1060, show that the protein conformation is identical, conferring a general
      character to the observation first made for retinoic acid receptor (RAR) that,
      for a given LBD, the agonist conformation is unique, the ligands adapting to the
      binding pocket. In all complexes, the A- to D-ring moieties of the ligands adopt
      the same conformation and form identical contacts with the protein. Differences
      are observed only for the 17beta-aliphatic chains that adapt their conformation
      to anchor the 25-hydroxyl group to His-305 and His-397. The inverted geometry of
      the C20 methyl group induces different paths of the aliphatic chains. The ligands
      exhibit a low-energy conformation for MC1288 and a more strained conformation for
      the two others. KH1060 compensates this energy cost by additional contacts. Based
      on the present data, the explanation of the superagonist effect is to be found in
      higher stability and longer half-life of the active complex, thereby excluding
      different conformations of the ligand binding domain.

PMID- 11344299
TI  - Evaluating the binding selectivity of transthyretin amyloid fibril inhibitors in
      blood plasma.
AB  - Transthyretin (TTR) tetramer dissociation and misfolding facilitate assembly into
      amyloid fibrils that putatively cause senile systemic amyloidosis and familial
      amyloid polyneuropathy. We have previously discovered more than 50 small
      molecules that bind to and stabilize tetrameric TTR, inhibiting amyloid fibril
      formation in vitro. A method is presented here to evaluate the binding
      selectivity of these inhibitors to TTR in human plasma, a complex biological
      fluid composed of more than 60 proteins and numerous small molecules. Our
      immunoprecipitation approach isolates TTR and bound small molecules from a
      biological fluid such as plasma, and quantifies the amount of small molecules
      bound to the protein by HPLC analysis. This approach demonstrates that only a
      small subset of the inhibitors that saturate the TTR binding sites in vitro do so
      in plasma. These selective inhibitors can now be tested in animal models of TTR
      amyloid disease to probe the validity of the amyloid hypothesis. This method
      could be easily extended to evaluate small molecule binding selectivity to any
      protein in a given biological fluid without the necessity of determining or
      guessing which other protein components may be competitors. This is a central
      issue to understanding the distribution, metabolism, activity, and toxicity of
      potential drugs.

PMID- 11344300
TI  - RNA-protein hybrid ribozymes that efficiently cleave any mRNA independently of
      the structure of the target RNA.
AB  - Ribozyme activity in vivo depends on achieving high-level expression,
      intracellular stability, target colocalization, and cleavage site access. At
      present, target site selection is problematic because of unforeseeable secondary
      and tertiary RNA structures that prevent cleavage. To overcome this design
      obstacle, we wished to engineer a ribozyme that could access any chosen site. To
      create this ribozyme, the constitutive transport element (CTE), an RNA motif that
      has the ability to interact with intracellular RNA helicases, was attached to our
      ribozymes so that the helicase-bound, hybrid ribozymes would be produced in
      cells. This modification significantly enhanced ribozyme activity in vivo,
      permitting cleavage of sites previously found to be inaccessible. To confer
      cleavage enhancement, the CTE must retain helicase-binding activity. Binding
      experiments demonstrated the likely involvement of RNA helicase(s). We found that
      attachment of the RNA motif to our tRNA ribozymes leads to cleavage in vivo at
      the chosen target site regardless of the local RNA secondary or tertiary
      structure.

PMID- 11344301
TI  - Three-dimensional domain swapping in p13suc1 occurs in the unfolded state and is
      controlled by conserved proline residues.
AB  - p13suc1 has two native states, a monomer and a domain-swapped dimer. We show that
      their folding pathways are connected by the denatured state, which introduces a
      kinetic barrier between monomer and dimer under native conditions. The barrier is
      lowered under conditions that speed up unfolding, thereby allowing, to our
      knowledge for the first time, a quantitative dissection of the energetics of
      domain swapping. The monomer-dimer equilibrium is controlled by two conserved
      prolines in the hinge loop that connects the exchanging domains. These two
      residues exploit backbone strain to specifically direct dimer formation while
      preventing higher-order oligomerization. Thus, the loop acts as a loaded
      molecular spring that releases tension in the monomer by adopting its alternative
      conformation in the dimer. There is an excellent correlation between domain
      swapping and aggregation, suggesting they share a common mechanism. These
      insights have allowed us to redesign the domain-swapping propensity of suc1 from
      a fully monomeric to a fully dimeric protein.

PMID- 11344302
TI  - Rck2, a member of the calmodulin-protein kinase family, links protein synthesis
      to high osmolarity MAP kinase signaling in budding yeast.
AB  - Rck2, a yeast Ser/Thr protein kinase homologous to mammalian calmodulin kinases,
      requires phosphorylation for activation. We provide evidence that in budding
      yeast, this step can be executed by the osmostress-activated mitogen-activated
      protein kinase Hog1. Rck2 phosphorylation was transiently increased during
      osmostress or in mutants with a hyperactive high osmolarity glycerol (HOG)
      pathway. This modification depended on catalytically active Hog1 kinase and two
      putative mitogen-activated protein kinase phosphorylation sites in Rck2.
      Immunokinase assays showed that Hog1 can directly phosphorylate Rck2 to stimulate
      its enzymatic activity toward translation elongation factor 2. We demonstrate
      that Hog1 and Rck2 are necessary for attenuation of protein synthesis in response
      to osmotic challenge and show that modification of elongation factor 2 induced by
      osmostress depends on Rck2 and Hog1 in vivo. Therefore, we propose that the
      transient down-regulation of protein synthesis after osmotic shock is a response
      not to damage but to an extracellular signal mediated by Hog1 and Rck2.

PMID- 11344303
TI  - Statistical modeling of large microarray data sets to identify stimulus-response
      profiles.
AB  - A statistical modeling approach is proposed for use in searching large microarray
      data sets for genes that have a transcriptional response to a stimulus. The
      approach is unrestricted with respect to the timing, magnitude or duration of the
      response, or the overall abundance of the transcript. The statistical model makes
      an accommodation for systematic heterogeneity in expression levels. Corresponding
      data analyses provide gene-specific information, and the approach provides a
      means for evaluating the statistical significance of such information. To
      illustrate this strategy we have derived a model to depict the profile expected
      for a periodically transcribed gene and used it to look for budding yeast
      transcripts that adhere to this profile. Using objective criteria, this method
      identifies 81% of the known periodic transcripts and 1,088 genes, which show
      significant periodicity in at least one of the three data sets analyzed. However,
      only one-quarter of these genes show significant oscillations in at least two
      data sets and can be classified as periodic with high confidence. The method
      provides estimates of the mean activation and deactivation times, induced and
      basal expression levels, and statistical measures of the precision of these
      estimates for each periodic transcript.

PMID- 11344304
TI  - Neuralized is essential for a subset of Notch pathway-dependent cell fate
      decisions during Drosophila eye development.
AB  - Neuralized (neur) is a neurogenic mutant of Drosophila in which many signaling
      events mediated by the Notch (N) receptor are disrupted. Here, we analyze the
      role of neur during eye development. Neur is required in a cell-autonomous
      fashion to restrict R8 and other photoreceptor fates and is involved in lateral
      inhibition of interommatidial bristles but is not required for induction of the
      cone cell fate. The latter contrasts with the absolute requirement for Suppressor
      of Hairless and the Enhancer of split-Complex for cone cell induction. Using gain
      of-function experiments, we further demonstrate that ectopic wild-type and
      truncated Neur proteins can interfere with multiple N-controlled aspects of eye
      development, including both neur-dependent and neur-independent processes.

PMID- 11344305
TI  - Vascular patterning defects associated with expression of activated Notch4 in
      embryonic endothelium.
AB  - Notch proteins function as receptors for membrane-bound ligands (Jagged and Delta
      like) to regulate cell-fate determination. We have investigated the role of Notch
      signaling in embryonic endothelium of the mouse by expressing an activated form
      of the Notch4 protein in vasculature under the regulation of the Flk1 (VEGFR)
      locus. Expression of activated Notch4 results in a growth and developmental delay
      and embryonic lethality at about 10 days postcoitum. The extent of the developing
      vasculature in mutant embryos was restricted, fewer small vessels were seen, and
      vascular networks were disorganized. The brain periphery of mutant embryos
      contained large dilated vessels with evidence of compromised vessel-wall
      integrity and large areas of necrosis; yolk-sac vasculature was abnormal.
      Expression of an activated form of Notch4 in embryonic vasculature leads to
      abnormal vessel structure and patterning, implicating the Notch pathway in phases
      of vascular development associated with vessel patterning and remodeling.

PMID- 11344306
TI  - Ecosystem impacts of three sequential hurricanes (Dennis, Floyd, and Irene) on
      the United States' largest lagoonal estuary, Pamlico Sound, NC.
AB  - Three sequential hurricanes, Dennis, Floyd, and Irene, affected coastal North
      Carolina in September and October 1999. These hurricanes inundated the region
      with up to 1 m of rainfall, causing 50- to 500-year flooding in the watershed of
      the Pamlico Sound, the largest lagoonal estuary in the United States and a key
      West Atlantic fisheries nursery. We investigated the ecosystem-level impacts on
      and responses of the Sound to the floodwater discharge. Floodwaters displaced
      three-fourths of the volume of the Sound, depressed salinity by a similar amount,
      and delivered at least half of the typical annual nitrogen load to this nitrogen
      sensitive ecosystem. Organic carbon concentrations in floodwaters entering
      Pamlico Sound via a major tributary (the Neuse River Estuary) were at least 2
      fold higher than concentrations under prefloodwater conditions. A cascading set
      of physical, chemical, and ecological impacts followed, including strong vertical
      stratification, bottom water hypoxia, a sustained increase in algal biomass,
      displacement of many marine organisms, and a rise in fish disease. Because of the
      Sound's long residence time ( approximately 1 year), we hypothesize that the
      effects of the short-term nutrient enrichment could prove to be multiannual. A
      predicted increase in the frequency of hurricane activity over the next few
      decades may cause longer-term biogeochemical and trophic changes in this and
      other estuarine and coastal habitats.

PMID- 11344307
TI  - Geometric constraints explain much of the species richness pattern in African
      birds.
AB  - The world contains boundaries (e.g., continental edge for terrestrial taxa) that
      impose geometric constraints on the distribution of species ranges. Thus,
      contrary to traditional thinking, the expected species richness pattern in
      absence of ecological or physiographical factors is unlikely to be uniform.
      Species richness has been shown to peak in the middle of a bounded one
      dimensional domain, even in the absence of ecological or physiographical factors.
      Because species ranges are not linear, an extension of the approach to two
      dimensions is necessary. Here we present a two-dimensional null model accounting
      for effects of geometric constraints. We use the model to examine the effects of
      continental edge on the distribution of terrestrial animals in Africa and compare
      the predictions with the observed pattern of species richness in birds endemic to
      the continent. Latitudinal, longitudinal, and two-dimensional patterns of species
      richness are predicted well from the modeled null effects alone. As expected,
      null effects are of high significance for wide ranging species only. Our results
      highlight the conceptual significance of an until recently neglected constraint
      from continental shape alone and support a more cautious analysis of species
      richness patterns at this scale.

PMID- 11344308
TI  - Molecular and genealogical evidence for a founder effect in Fanconi anemia
      families of the Afrikaner population of South Africa.
AB  - Fanconi anemia (FA) is a rare, genetically heterogeneous autosomal recessive
      disorder associated with progressive aplastic anemia, congenital abnormalities,
      and cancer. FA has a very high incidence in the Afrikaner population of South
      Africa, possibly due to a founder effect. Previously we observed allelic
      association between polymorphic markers flanking the FA group A gene (FANCA) and
      disease chromosomes in Afrikaners. We genotyped 26 FA families with
      microsatellite and single nucleotide polymorphic markers and detected five FANCA
      haplotypes. Mutation scanning of the FANCA gene revealed association of these
      haplotypes with four different mutations. The most common was an intragenic
      deletion of exons 12-31, accounting for 60% of FA chromosomes in 46 unrelated
      Afrikaner FA patients, while two other mutations accounted for an additional 20%.
      Screening for these mutations in the European populations ancestral to the
      Afrikaners detected one patient from the Western Ruhr region of Germany who was
      heterozygous for the major deletion. The mutation was associated with the same
      unique FANCA haplotype as in Afrikaner patients. Genealogical investigation of 12
      Afrikaner families with FA revealed that all were descended from a French
      Huguenot couple who arrived at the Cape on June 5, 1688, whereas mutation
      analysis showed that the carriers of the major mutation were descendants of this
      same couple. The molecular and genealogical evidence is consistent with
      transmission of the major mutation to Western Germany and the Cape near the end
      of the 17th century, confirming the existence of a founder effect for FA in South
      Africa.

PMID- 11344309
TI  - Evolutionary relationships among Rel domains indicate functional diversification
      by recombination.
AB  - The recent sequencing of several complete genomes has made it possible to track
      the evolution of large gene families by their genomic structure. Following the
      large-scale association of exons encoding domains with well defined functions in
      invertebrates could be useful in predicting the function of complex multidomain
      proteins in mammals produced by accretion of domains. With this objective, we
      have determined the genomic structure of the 14 genes in invertebrates and
      vertebrates that contain rel domains. The sequence encoding the rel domain is
      defined by intronic boundaries and has been recombined with at least three
      structurally and functionally distinct genomic sequences to generate coding
      sequences for: (i) the rel/Dorsal/NFkappaB proteins that are retained in the
      cytoplasm by IkB-like proteins; (ii) the NFATc proteins that sense calcium
      signals and undergo cytoplasmic-to-nuclear translocation in response to
      dephosphorylation by calcineurin; and (iii) the TonEBP tonicity-responsive
      proteins. Remarkably, a single exon in each NFATc family member encodes the
      entire Ca(2+)/calcineurin sensing region, including nuclear import/export,
      calcineurin-binding, and substrate regions. The Rel/Dorsal proteins and the
      TonEBP proteins are present in Drosophila but not Caenorhabditis elegans. On the
      other hand, the calcium-responsive NFATc proteins are present only in
      vertebrates, suggesting that the NFATc family is dedicated to functions specific
      to vertebrates such as a recombinational immune response, cardiovascular
      development, and vertebrate-specific aspects of the development and function of
      the nervous system.

PMID- 11344310
TI  - Cooperative enhancement of specificity in a lattice of T cell receptors.
AB  - Two of the most important models to account for the specificity and sensitivity
      of the T cell receptor (TCR) are the kinetic proofreading and serial ligation
      models. However, although kinetic proofreading provides a means for individual
      TCRs to measure accurately the length of time they are engaged and signal
      appropriately, the stochastic nature of ligand dissociation means the kinetic
      proofreading model implies that at high concentrations the response of the cell
      will be relatively nonspecific. Recent ligand experiments have revealed the
      phenomenon of both negative and positive crosstalk among neighboring TCRs. By
      using a Monte Carlo simulation of a lattice of TCRs, we integrate receptor
      crosstalk with the kinetic proofreading and serial ligation models and discover
      that receptor cooperativity can enhance T cell specificity significantly at a
      very modest cost to the sensitivity of the response.

PMID- 11344311
TI  - Involvement of a human gene related to the Drosophila spen gene in the recurrent
      t(1;22) translocation of acute megakaryocytic leukemia.
AB  - The recurrent t(1;22)(p13;q13) translocation is exclusively associated with
      infant acute megakaryoblastic leukemia. We have identified the two genes involved
      in this translocation. Both genes possess related sequences in the Drosophila
      genome. The chromosome 22 gene (megakaryocytic acute leukemia, MAL) product is
      predicted to be involved in chromatin organization, and the chromosome 1 gene
      (one twenty-two, OTT) product is related to the Drosophila split-end (spen)
      family of proteins. Drosophila genetic experiments identified spen as involved in
      connecting the Raf and Hox pathways. Because almost all of the sequences and all
      of the identified domains of both OTT and MAL proteins are included in the
      predicted fusion protein, the OTT-MAL fusion could aberrantly modulate chromatin
      organization, Hox differentiation pathways, or extracellular signaling.

PMID- 11344312
TI  - Avicins: triterpenoid saponins from Acacia victoriae (Bentham) induce apoptosis
      by mitochondrial perturbation.
AB  - Anticancer agents target various subcellular components and trigger apoptosis in
      chemosensitive cells. We have recently reported the tumor cell growth inhibitory
      properties of a mixture of triterpenoid saponins obtained from an Australian
      desert tree (Leguminosae) Acacia victoriae (Bentham). Here we report the
      purification of this mixture into two biologically pure components called avicins
      that contain an acacic acid core with two acyclic monoterpene units connected by
      a quinovose sugar. We demonstrate that the mixture of triterpenoid saponins and
      avicins induce apoptosis in the Jurkat human T cell line by affecting the
      mitochondrial function. Avicin G induced cytochrome c release within 30-120 min
      in whole cells and within a minute in the cell-free system. Caspase inhibitors
      DEVD or zVAD-fmk had no effect on cytochrome c release, suggesting the direct
      action of avicin G on the mitochondria. Activation of caspase-3 and total
      cleavage of poly(ADP-ribose) polymerase (PARP) occurred between 2 and 6 h
      posttreatment with avicins by zVAD-fmk. Interestingly, in the treated cells no
      significant changes in the membrane potential preceded or accompanied cytochrome
      c release. A small decrease in the generation of reactive oxygen species (ROS)
      was measured. The study of these evolutionarily ancient compounds may represent
      an interesting paradigm for the application of chemical ecology and chemical
      biology to human health.

PMID- 11344313
TI  - Large carbon isotope fractionation associated with oxidation of methyl halides by
      methylotrophic bacteria.
AB  - The largest biological fractionations of stable carbon isotopes observed in
      nature occur during production of methane by methanogenic archaea. These
      fractionations result in substantial (as much as approximately 70 per thousand)
      shifts in delta(13)C relative to the initial substrate. We now report that a
      stable carbon isotopic fractionation of comparable magnitude (up to 70 per
      thousand) occurs during oxidation of methyl halides by methylotrophic bacteria.
      We have demonstrated biological fractionation with whole cells of three
      methylotrophs (strain IMB-1, strain CC495, and strain MB2) and, to a lesser
      extent, with the purified cobalamin-dependent methyltransferase enzyme obtained
      from strain CC495. Thus, the genetic similarities recently reported between
      methylotrophs, and methanogens with respect to their pathways for C(1)-unit
      metabolism are also reflected in the carbon isotopic fractionations achieved by
      these organisms. We found that only part of the observed fractionation of carbon
      isotopes could be accounted for by the activity of the corrinoid
      methyltransferase enzyme, suggesting fractionation by enzymes further along the
      degradation pathway. These observations are of potential biogeochemical
      significance in the application of stable carbon isotope ratios to constrain the
      tropospheric budgets for the ozone-depleting halocarbons, methyl bromide and
      methyl chloride.

PMID- 11344314
TI  - Multiple maternal origins and weak phylogeographic structure in domestic goats.
AB  - Domestic animals have played a key role in human history. Despite their
      importance, however, the origins of most domestic species remain poorly
      understood. We assessed the phylogenetic history and population structure of
      domestic goats by sequencing a hypervariable segment (481 bp) of the mtDNA
      control region from 406 goats representing 88 breeds distributed across the Old
      World. Phylogeographic analysis revealed three highly divergent goat lineages
      (estimated divergence >200,000 years ago), with one lineage occurring only in
      eastern and southern Asia. A remarkably similar pattern exists in cattle, sheep,
      and pigs. These results, combined with recent archaeological findings, suggest
      that goats and other farm animals have multiple maternal origins with a possible
      center of origin in Asia, as well as in the Fertile Crescent. The pattern of goat
      mtDNA diversity suggests that all three lineages have undergone population
      expansions, but that the expansion was relatively recent for two of the lineages
      (including the Asian lineage). Goat populations are surprisingly less genetically
      structured than cattle populations. In goats only approximately 10% of the mtDNA
      variation is partitioned among continents. In cattle the amount is >/=50%. This
      weak structuring suggests extensive intercontinental transportation of goats and
      has intriguing implications about the importance of goats in historical human
      migrations and commerce.

PMID- 11344315
TI  - Effect of the N1 residue on the stability of the alpha-helix for all 20 amino
      acids.
AB  - N1 is the first residue in an alpha-helix. We have measured the contribution of
      all 20 amino acids to the stability of a small helical peptide CH(3)CO
      XAAAAQAAAAQAAGY-NH(2) at the N1 position. By substituting every residue into the
      N1 position, we were able to investigate the stabilizing role of each amino acid
      in an isolated context. The helix content of each of the 20 peptides was measured
      by circular dichroism (CD) spectroscopy. The data were analyzed by our modified
      Lifson-Roig helix-coil theory, which includes the n1 parameter, to find free
      energies for placing a residue into the N1 position. The rank order for free
      energies is Asp(-), Ala > Glu(-) > Glu(0) > Trp, Leu, Ser > Asp(0), Thr, Gln,
      Met, Ile > Val, Pro > Lys(+), Arg, His(0) > Cys, Gly > Phe > Asn, Tyr, His(+). N1
      preferences are clearly distinct from preferences for the preceding N-cap and
      alpha-helix interior. pK(a) values were measured for Asp, Glu, and His, and
      protonation-free energies were calculated for Asp and Glu. The dissociation of
      the Asp proton is less favorable than that of Glu, and this reflects its
      involvement in a stronger stabilizing interaction at the N terminus. Proline is
      not energetically favored at the alpha-helix N terminus despite having a high
      propensity for this position in crystal structures. The data presented are of
      value both in rationalizing mutations at N1 alpha-helix sites in proteins and in
      predicting the helix contents of peptides.

PMID- 11344316
TI  - Identification of four proteins from the small subunit of the mammalian
      mitochondrial ribosome using a proteomics approach.
AB  - Proteins in the small subunit of the mammalian mitochondrial ribosome were
      separated by two-dimensional polyacrylamide gel electrophoresis. Four individual
      proteins were subjected to in-gel Endoprotease Lys-C digestion. The sequences of
      selected proteolytic peptides were obtained by electrospray tandem mass
      spectrometry. Peptide sequences obtained from in-gel digestion of individual
      spots were used to screen human, mouse, and rat expressed sequence tag databases,
      and complete consensus cDNAs for these species were deduced in silico. The
      corresponding protein sequences were characterized by comparison to known
      ribosomal proteins in protein databases. Four different classes of mammalian
      mitochondrial small subunit ribosomal proteins were identified. Only two of these
      proteins have significant sequence similarities to ribosomal proteins from
      prokaryotes. These proteins are homologs to Escherichia coli S9 and S5 proteins.
      The presence of these newly identified mitochondrial ribosomal proteins are also
      investigated in the Drosophila melanogaster, Caenorhabditis elegans, and in the
      genomes of several fungi.

PMID- 11344317
TI  - Conformational analysis of putative regulatory subunit D of the toluene/o-xylene
      monooxygenase complex from Pseudomonas stutzeri OX1.
AB  - A gene cluster isolated from Pseudomonas stutzeri OX1 genomic DNA and containing
      six ORFs codes for toluene/o-xylene-monooxygenase. The putative regulatory D
      subunit was expressed in Escherichia coli and purified. Its protein sequence was
      verified by mass spectrometry mapping and found to be identical to the sequence
      predicted on the basis of the DNA sequence. The surface topology of subunit D in
      solution was probed by limited proteolysis carried out under strictly controlled
      conditions using several proteases as proteolytic probes. The same experiments
      were carried out on the homologous P2 component of the multicomponent phenol
      hydroxylase from Pseudomonas putida CF600. The proteolytic fragments released
      from both proteins in their native state were analyzed by electrospray mass
      spectrometry, and the preferential cleavage sites were assessed. The results
      indicated that despite the relatively high similarity between the sequences of
      the two proteins, some differences in the distribution of preferential
      proteolytic cleavages were detected, and a much higher conformational flexibility
      of subunit D was inferred. Moreover, automatic modeling of subunit D was
      attempted, based on the known three-dimensional structure of P2. Our results
      indicate that, at least in this case, standard modeling procedures based on
      automatic alignment on the structure of P2 fail to produce a model consistent
      with limited proteolysis experimental data. Thus, it is our opinion that reliable
      techniques such as limited proteolysis can be employed to test three-dimensional
      models and highlight problems in automatic model building.

PMID- 11344318
TI  - Reduced antibody response to streptavidin through site-directed mutagenesis.
AB  - Streptavidin provides an effective receptor for biotinylated tumoricidal
      molecules, including radionuclides, when conjugated to an antitumor antibody and
      administered systemically. Ideally, one would like to administer this bacterial
      protein to patients repeatedly, so as to maximize the antitumor effect without
      eliciting an immune response. Therefore, we attempted to reduce the antigenicity
      of streptavidin by mutating surface residues capable of forming high energy ionic
      or hydrophobic interactions. A crystallographic image of streptavidin was
      examined to identify residues with solvent-exposed side chains and residues
      critical to streptavidin's structure or function, and to define loops. Mutations
      were incorporated cumulatively into the protein sequence. Mutants were screened
      for tetramer formation, biotin dissociation, and reduced immunoreactivity with
      pooled patient sera. Patient antisera recognized one minor continuous epitope
      with binding locus at residue E101 and one major discontinuous epitope involving
      amino acid residues E51 and Y83. Mutation of residues E51, Y83, R53, and E116
      reduced reactivity with patient sera to <10% that of streptavidin, but these
      mutations were no less antigenic in rabbits. Mutant 37, with 10 amino acid
      substitutions, was only 20% as antigenic as streptavidin. Rabbits immunized with
      either streptavidin or mutant 37 failed to recognize the alternative antigen.
      Biotin dissociated from mutant 37 four to five times faster than from
      streptavidin. Residues were identified with previously undescribed impact on
      biotin binding and protein folding. Thus, substitution of charged, aromatic, or
      large hydrophobic residues on the surface of streptavidin with smaller neutral
      residues reduced the molecule's ability to elicit an immune response in rabbits.

PMID- 11344319
TI  - HMG-D complexed to a bulge DNA: an NMR model.
AB  - An NMR model is presented for the structure of HMG-D, one of the Drosophila
      counterparts of mammalian HMG1/2 proteins, bound to a particular distorted DNA
      structure, a dA(2) DNA bulge. The complex is in fast to intermediate exchange on
      the NMR chemical shift time scale and suffers substantial linebroadening for the
      majority of interfacial resonances. This essentially precludes determination of a
      high-resolution structure for the interface based on NMR data alone. However, by
      introducing a small number of additional constraints based on chemical shift and
      linewidth footprinting combined with analogies to known structures, an ensemble
      of model structures was generated using a computational strategy equivalent to
      that for a conventional NMR structure determination. We find that the base pair
      adjacent to the dA(2) bulge is not formed and that the protein recognizes this
      feature in forming the complex; intermolecular NOE enhancements are observed from
      the sidechain of Thr 33 to all four nucleotides of the DNA sequence step adjacent
      to the bulge. Our results form the first experimental demonstration that when
      binding to deformed DNA, non-sequence-specific HMG proteins recognize the
      junction between duplex and nonduplex DNA. Similarities and differences of the
      present structural model relative to other HMG-DNA complex structures are
      discussed.

PMID- 11344320
TI  - In vivo assembly of aspartate transcarbamoylase from fragmented and circularly
      permuted catalytic polypeptide chains.
AB  - Previous studies on Escherichia coli aspartate transcarbamoylase (ATCase)
      demonstrated that active, stable enzyme was formed in vivo from complementing
      polypeptides of the catalytic (c) chain encoded by gene fragments derived from
      the pyrBI operon. However, the enzyme lacked the allosteric properties
      characteristic of wild-type ATCase. In order to determine whether the loss of
      homotropic and heterotropic properties was attributable to the location of the
      interruption in the polypeptide chain rather than to the lack of continuity, we
      constructed a series of fragmented genes so that the breaks in the polypeptide
      chains would be dispersed in different domains and diverse regions of the
      structure. Also, analogous molecules containing circularly permuted c chains with
      altered termini were constructed for comparison with the ATCase molecules
      containing fragmented c chains. Studies were performed on four sets of ATCase
      molecules containing cleaved c chains at positions between residues 98 and 99,
      121 and 122, 180 and 181, and 221 and 222; the corresponding circularly permuted
      chains had N termini at positions 99, 122, 181, and 222. All of the ATCase
      molecules containing fragmented or circularly permuted c chains exhibited the
      homotropic and heterotropic properties characteristic of the wild-type enzyme.
      Hill coefficients (n(H:)) and changes in them upon the addition of ATP and CTP
      were similar to those observed with wild-type ATCase. In addition, the
      conformational changes revealed by the decrease in sedimentation coefficient upon
      the addition of a bisubstrate analog were virtually identical to that for the
      wild-type enzyme. Differential scanning calorimetry showed that neither the
      breakage of the polypeptide chains nor the newly formed covalent bond between the
      termini in the wild-type enzyme had a significant impact on the thermal stability
      of the assembled dodecamers. The studies demonstrate that continuity of the
      polypeptide chain within structural domains is not essential for the assembly,
      activity, and allosteric properties of ATCase.

PMID- 11344321
TI  - Random circular permutation leading to chain disruption within and near alpha
      helices in the catalytic chains of aspartate transcarbamoylase: effects on
      assembly, stability, and function.
AB  - A collection of circularly permuted catalytic chains of aspartate
      transcarbamoylase (ATCase) has been generated by random circular permutation of
      the pyrB gene. From the library of ATCases containing permuted polypeptide
      chains, we have chosen for further investigation nine ATCase variants whose
      catalytic chains have termini located within or close to an alpha helix. All of
      the variants fold and assemble into dodecameric holoenzymes with similar
      sedimentation coefficients and slightly reduced thermal stabilities. Those
      variants disrupted within three different helical regions in the wild-type
      structure show no detectable enzyme activity and no apparent binding of the
      bisubstrate analog N:-phosphonacetyl-L-aspartate. In contrast, two variants whose
      termini are just within or adjacent to other alpha helices are catalytically
      active and allosteric. As expected, helical disruptions are more destabilizing
      than loop disruptions. Nonetheless, some catalytic chains lacking continuity
      within helical regions can assemble into stable holoenzymes comprising six
      catalytic and six regulatory chains. For seven of the variants, continuity within
      the helices in the catalytic chains is important for enzyme activity but not
      necessary for proper folding, assembly, and stability of the holoenzyme.

PMID- 11344322
TI  - Solution structure and backbone dynamics of an omega-conotoxin precursor.
AB  - Nuclear magnetic resonance spectroscopy was used to characterize the solution
      structure and backbone dynamics of a putative precursor form of omega-conotoxin
      MVIIA, a 25-amino-acid residue peptide antagonist of voltage-gated Ca(2+)
      channels. The mature peptide is found in the venom of a fish-hunting marine snail
      Conus magus and contains an amidated carboxyl terminus that is generated by
      oxidative cleavage of a Gly residue. The form examined in this study is identical
      to the mature peptide except for the presence of the unmodified carboxy-terminal
      Gly. This form, referred to as omega-MVIIA-Gly, has previously been shown to
      refold and form its disulfides more efficiently than the mature form, suggesting
      that the presence of the terminal Gly may favor folding in vivo. The nuclear
      magnetic resonance (NMR) structure determination indicated that the fold of omega
      MVIIA-Gly is very similar to that previously determined for the mature form, but
      revealed that the terminal Gly residue participates in a network of hydrogen
      bonds involving both backbone and side chain atoms, very likely accounting for
      the enhanced stability and folding efficiency. (15)N relaxation experiments
      indicated that the backbone is well ordered on the nanosecond time scale but that
      residues 9-15 undergo a conformational exchange processes with a time constant of
      approximately 35 microseconds. Other studies have implicated this segment in the
      binding of the peptide to its physiological target, and the observed motions may
      play a role in allowing the peptide to enter the binding site

PMID- 11344323
TI  - Characterization of the N-terminal repeat domain of Escherichia coli ClpA-A class
      I Clp/HSP100 ATPase.
AB  - The ClpA, ClpB, and ClpC subfamilies of the Clp/HSP100 ATPases contain a
      conserved N-terminal region of approximately 150 residues that consists of two
      approximate sequence repeats. This sequence from the Escherichia coli ClpA enzyme
      is shown to encode an independent structural domain (the R domain) that is
      monomeric and approximately 40% alpha-helical. A ClpA fragment lacking the R
      domain showed ATP-dependent oligomerization, protein-stimulated ATPase activity,
      and the ability to complex with the ClpP peptidase and mediate degradation of
      peptide and protein substrates, including casein and ssrA-tagged proteins.
      Compared with the activities of the wild-type ClpA, however, those of the ClpA
      fragment missing the R domain were reduced. These results indicate that the R
      domain is not required for the basic recognition, unfolding, and translocation
      functions that allow ClpA-ClpP to degrade some protein substrates, but they
      suggest that it may play a role in modulating these activities.

PMID- 11344324
TI  - Identification of intrinsic order and disorder in the DNA repair protein XPA.
AB  - The DNA-repair protein XPA is required to recognize a wide variety of bulky
      lesions during nucleotide excision repair. Independent NMR solution structures of
      a human XPA fragment comprising approximately 40% of the full-length protein, the
      minimal DNA-binding domain, revealed that one-third of this molecule was
      disordered. To better characterize structural features of full-length XPA, we
      performed time-resolved trypsin proteolysis on active recombinant Xenopus XPA
      (xXPA). The resulting proteolytic fragments were analyzed by electrospray
      ionization interface coupled to a Fourier transform ion cyclotron resonance mass
      spectrometry and SDS-PAGE. The molecular weight of the full-length xXPA
      determined by mass spectrometry (30922.02 daltons) was consistent with that
      calculated from the sequence (30922.45 daltons). Moreover, the mass spectrometric
      data allowed the assignment of multiple xXPA fragments not resolvable by SDS
      PAGE. The neural network program Predictor of Natural Disordered Regions (PONDR)
      applied to xXPA predicted extended disordered N- and C-terminal regions with an
      ordered internal core. This prediction agreed with our partial proteolysis
      results, thereby indicating that disorder in XPA shares sequence features with
      other well-characterized intrinsically unstructured proteins. Trypsin cleavages
      at 30 of the possible 48 sites were detected and no cleavage was observed in an
      internal region (Q85-I179) despite 14 possible cut sites. For the full-length
      xXPA, there was strong agreement among PONDR, partial proteolysis data, and the
      NMR structure for the corresponding XPA fragment.

PMID- 11344325
TI  - Physicochemical consequences of the perdeuteriation of glutathione S-transferase
      from S. japonicum.
AB  - Glutathione S:-transferase (GST) from Schistosoma japonicum has been prepared in
      both normal protiated (pGST) and fully deuteriated (dGST) form by recombinant DNA
      technology. Electrospray mass spectrometry showed that the level of deuteriation
      in dGST was 96% and was homogeneous across the sample. This result is attributed
      to the use of a deuterium-tolerant host Escherichia coli strain in the
      preparation of the protein. 10 heteroatom-bound deuteriums (in addition to the
      carbon-bound deuteriums) were resistant to exchange when dGST was incubated in
      protiated buffer. The physicochemical and biological properties of the two
      proteins were compared. dGST was relatively less stable to heat denaturation and
      to proteolytic cleavage than was pGST. The midpoint transition temperature for
      pGST was 54.9 degrees C, whereas that for dGST was 51.0 degrees C. Static light
      scattering measurements revealed that the association behavior of dGST is also
      different from that of pGST. The perdeuteriated enzyme shows a tendency to
      associate into dimers of the fundamental dimer. This is in contrast with results
      that have been obtained for other perdeuteriated proteins in which
      perdeuteriation has been shown to promote dissociation of aggregates. dGST showed
      a similar K(m) to pGST; similar results had been obtained previously with
      bacterial alkaline phosphatase. However, whereas the alkaline phosphatase showed
      a reduced rate of catalysis on deuteriation, dGST exhibited a slightly higher
      rate of catalysis than pGST. It is clear that the bulk substitution of deuterium
      for protium has significant effects on the properties of proteins. Until many
      more examples have been studied, it will be difficult to predict these effects
      for any given protein. Nevertheless, deuteriation represents an intriguing method
      of preparing functional analogs of recombinant proteins.

PMID- 11344326
TI  - A general method for the quantitative analysis of functional chimeras:
      applications from site-directed mutagenesis and macromolecular association.
AB  - Two new parameters, I: and C:, are introduced for the quantitative evaluation of
      functional chimeras: I: (impact) and C: (context dependence) are the free energy
      difference and sum, respectively, of the effects on a given property measured in
      forward and retro chimeras. The forward chimera is made by substitution of a part
      "a" from ensemble A into the analogous position of homologous ensemble B (S:(B -
      > A)). The C: value is a measure of the interaction of the interrogated position
      with its surroundings, whereas I: is an expression of the quantitative importance
      of the probed position. Both I: and C: vary with the evaluated property, for
      example, kinetics, binding, thermostability, and so forth. The retro chimera is
      the reverse substitution of the analogous part "b" from B into A, S:(A --> B).
      The I: and C: values derived from original data for forward and retro mutations
      in aspartate and tyrosine aminotransferase, from literature data for quasi domain
      exchange in oncomodulin and for the interaction of Tat with bovine and human TAR
      are evaluated. The most salient derived conclusions are, first, that Thr 109
      (AATase) or Ser 109 (TATase) is an important discriminator for dicarboxylic acid
      selectivity by these two enzymes (I: < -2.9 kcal/mol). The T109S mutation in
      AATase produces a nearly equal and opposite effect to S109T in TATase (C: < 0.4
      kcal/mol). Second, an I: value of 5.5 kcal/mol describes the effects of mirror
      mutations D94S (site 1) and S55D (site 2) in the Ca(2+) binding sites of
      oncomodulin on Ca(2+) affinity. The second mirror set, G98D (site 1) and D59G
      (site 2), yields a smaller impact (I: = -3.4 kcal/mol) on Ca(2+) binding;
      however, the effect is significantly more nearly context independent (C: = -0.6
      versus C: = -2.7 kcal/mol). Third, the stem and loop regions of HIV and BIV TAR
      are predominantly responsible for the species specific interaction with BIV
      Tat(65-81) (I: = -1.5 to -1.6 kcal/mol), whereas I: = 0.1 kcal/mol for bulge TAR
      chimeras. The C: values are from -0.3 to -1.2 kcal/mol. The analysis described
      should have important applications to protein design.

PMID- 11344327
TI  - Solution structure of the DNA-binding domain of the TyrR protein of Haemophilus
      influenzae.
AB  - The TyrR protein of Haemophilus influenzae is a 36-kD transcription factor whose
      major function is to control the expression of genes important in the
      biosynthesis and transport of aromatic amino acids. Using (1)H and (15)N NMR
      spectroscopy, we have determined the 3D solution structure of the TyrR C-terminal
      DNA-binding domain (DBD) containing residues from 258 to 318 (TyrR[258-318]). The
      NMR results show that this segment of TyrR consists of a potential hinge helix at
      its N terminus (residues 263-270) as well as three well-defined alpha-helices
      extending from residues 277-289 (HR-2), 293-300 (HR-1), and 304-314 (HR). Helix
      HR-1 and HR fold in a typical helix-turn-helix (HTH) motif. The three helices and
      the hinge helix are tightly bound together by hydrophobic interaction and
      hydrogen bonds. Several hydrophilic residues whose side chains may directly
      interact with DNA are identified. A hydrophobic patch that may be part of the
      interaction surface between the domains of TyrR protein is also observed.
      Comparisons with the structures of other HTH DNA-binding proteins reveal that in
      terms of the spatial orientation of the three helices, this protein most closely
      resembles the cap family.

PMID- 11344328
TI  - CODA: a combined algorithm for predicting the structurally variable regions of
      protein models.
AB  - CODA, an algorithm for predicting the variable regions in proteins, combines
      FREAD a knowledge based approach, and PETRA, which constructs the region ab
      initio. FREAD selects from a database of protein structure fragments with
      environmentally constrained substitution tables and other rule-based filters.
      FREAD was parameterized and tested on over 3000 loops. The average root mean
      square deviation ranged from 0.78 A for three residue loops to 3.5 A for eight
      residue loops on a nonhomologous test set. CODA clusters the predictions from the
      two independent programs and makes a consensus prediction that must pass a set of
      rule-based filters. CODA was parameterized and tested on two unrelated separate
      sets of structures that were nonhomologous to one another and those found in the
      FREAD database. The average root mean square deviation in the test set ranged
      from 0.76 A for three residue loops to 3.09 A for eight residue loops. CODA shows
      a general improvement in loop prediction over PETRA and FREAD individually. The
      improvement is far more marked for lengths six and upward, probably as the
      predictive power of PETRA becomes more important. CODA was further tested on
      several model structures to determine its applicability to the modeling
      situation. A web server of CODA is available at http://www
      cryst.bioc.cam.ac.uk/~charlotte/Coda/search_coda.html.

PMID- 11344329
TI  - Leucine 41 is a gate for water entry in the reduction of Clostridium pasteurianum
      rubredoxin.
AB  - Biological electron transfer is an efficient process even though the distances
      between the redox moieties are often quite large. It is therefore of great
      interest to gain an understanding of the physical basis of the rates and driving
      forces of these reactions. The structural relaxation of the protein that occurs
      upon change in redox state gives rise to the reorganizational energy, which is
      important in the rates and the driving forces of the proteins involved. To
      determine the structural relaxation in a redox protein, we have developed methods
      to hold a redox protein in its final oxidation state during crystallization while
      maintaining the same pH and salt conditions of the crystallization of the protein
      in its initial oxidation state. Based on 1.5 A resolution crystal structures and
      molecular dynamics simulations of oxidized and reduced rubredoxins (Rd) from
      Clostridium pasteurianum (Cp), the structural rearrangements upon reduction
      suggest specific mechanisms by which electron transfer reactions of rubredoxin
      should be facilitated. First, expansion of the [Fe-S] cluster and concomitant
      contraction of the NH...S hydrogen bonds lead to greater electrostatic
      stabilization of the extra negative charge. Second, a gating mechanism caused by
      the conformational change of Leucine 41, a nonpolar side chain, allows transient
      penetration of water molecules, which greatly increases the polarity of the redox
      site environment and also provides a source of protons. Our method of producing
      crystals of Cp Rd from a reducing solution leads to a distribution of water
      molecules not observed in the crystal structure of the reduced Rd from Pyrococcus
      furiosus. How general this correlation is among redox proteins must be determined
      in future work. The combination of our high-resolution crystal structures and
      molecular dynamics simulations provides a molecular picture of the structural
      rearrangement that occurs upon reduction in Cp rubredoxin.

PMID- 11344330
TI  - Single amino acid substitutions on the surface of Escherichia coli maltose
      binding protein can have a profound impact on the solubility of fusion proteins.
AB  - Proteins are commonly fused to Escherichia coli maltose-binding protein (MBP) to
      enhance their yield and facilitate their purification. In addition, the stability
      and solubility of a passenger protein can often be improved by fusing it to MBP.
      In a previous comparison with two other highly soluble fusion partners, MBP was
      decidedly superior at promoting the solubility of a range of aggregation-prone
      proteins. To explain this observation, we proposed that MBP could function as a
      general molecular chaperone in the context of a fusion protein by binding to
      aggregation-prone folding intermediates of passenger proteins and preventing
      their self-association. The ligand-binding cleft in MBP was considered a likely
      site for peptide binding because of its hydrophobic nature. We tested this
      hypothesis by systematically replacing hydrophobic amino acid side chains in and
      around the cleft with glutamic acid. None of these mutations affected the yield
      or solubility of MBP in its unfused state. Each MBP was then tested for its
      ability to promote solubility when fused to three passenger proteins: green
      fluorescent protein, p16, and E6. Mutations within the maltose-binding cleft
      (W62E, A63E, Y155E, W230E, and W340E) had little or no effect on the solubility
      of the fusion proteins. In contrast, three mutations near one end of the cleft
      (W232E, Y242E, and I317E) dramatically reduced the solubility of the same fusion
      proteins. The mutations with the most profound effect on solubility were shown to
      reduce the global stability of MBP.

PMID- 11344331
TI  - Effects of charged amino acids at b and c heptad positions on specificity and
      stability of four-chain coiled coils.
AB  - An understanding of the balance of chemical forces responsible for protein
      stability and specificity of structure is essential for the success of efforts in
      protein design. Specifically, electrostatic interactions between charged amino
      acids have been explored extensively to understand the contribution of this force
      to protein stability. Much research on the importance of electrostatic
      interactions as specificity and stability determinants in two-stranded coiled
      coils has been done, but there remains significant controversy about the
      magnitude of the attractive forces using such systems. We have developed a four
      stranded coiled-coil system with charged residues incorporated at b and c heptad
      positions to explore the role of charge interactions. Here, we test
      quantitatively the effects of varying sidechain length on the magnitude of such
      electrostatic interactions. We synthesized peptides containing either aspartate
      or ornithine at both b and c heptad positions and tested their ability to self
      associate and to hetero-associate with one another and with peptides containing
      glutamate or lysine at the same positions. We find that interactions between
      glutamate and either lysine or ornithine are more favorable than the
      corresponding interactions involving aspartate. In each case, charged
      interactions provide additional stability to coiled coils, although helix
      propensity effects may play a significant role in determining the overall
      stability of these structures.

PMID- 11344332
TI  - Crystal structure of threonine synthase from Arabidopsis thaliana.
AB  - Threonine synthase (TS) is a PLP-dependent enzyme that catalyzes the last
      reaction in the synthesis of threonine from aspartate. In plants, the methionine
      pathway shares the same substrate, O-phospho-L-homoserine (OPH), and TS is
      activated by S-adenosyl-methionine (SAM), a downstream product of methionine
      synthesis. This positive allosteric effect triggered by the product of another
      pathway is specific to plants. The crystal structure of Arabidopsis thaliana apo
      threonine synthase was solved at 2.25 A resolution from triclinic crystals using
      MAD data from the selenomethionated protein. The structure reveals a four-domain
      dimer with a two-stranded beta-sheet arm protruding from one monomer onto the
      other. This domain swap could form a lever through which the allosteric effect is
      transmitted. The N-terminal domain (domain 1) has a unique fold and is partially
      disordered, whereas the structural core (domains 2 and 3) shares the functional
      domain of PLP enzymes of the same family. It also has similarities with SAM
      dependent methyltransferases. Structure comparisons allowed us to propose
      potential sites for pyridoxal-phosphate and SAM binding on TS; they are close to
      regions that are disordered in the absence of these molecules.

PMID- 11344333
TI  - Designed heterodimerizing leucine zippers with a ranger of pIs and stabilities up
      to 10(-15) M.
AB  - We have designed a heterodimerizing leucine zipper system to target a
      radionuclide to prelocalized noninternalizing tumor-specific antibodies. The
      modular nature of the leucine zipper allows us to iteratively use design rules to
      achieve specific homodimer and heterodimer affinities. We present circular
      dichroism thermal denaturation measurements on four pairs of heterodimerizing
      leucine zippers. These peptides are 47 amino acids long and contain four or five
      pairs of electrostatically attractive g <--> e' (i, i' +5) interhelical
      heterodimeric interactions. The most stable heterodimer consists of an acidic
      leucine zipper and a basic leucine zipper that melt as homodimers in the micro
      (T(m) = 28 degrees C) or nanomolar (T(m) = 40 degrees C) range, respectively, but
      heterodimerize with a T(m) >90 degrees C, calculated to represent femtamolar
      affinities. Modifications to this pair of acidic and basic zippers, designed to
      destabilize homodimerization, resulted in peptides that are unstructured monomers
      at 4 microM and 6 degrees C but that heterodimerize with a T(m) = 74 degrees C or
      K(d(37)) = 1.1 x 10(-11) M. A third heterodimerizing pair was designed to have a
      more neutral isoelectric focusing point (pI) and formed a heterodimer with T(m) =
      73 degrees C. We can tailor this heterodimerizing system to achieve
      pharmacokinetics aimed at optimizing targeted killing of cancer cells.

PMID- 11344334
TI  - Unusual evolutionary history of the tRNA splicing endonuclease EndA: relationship
      to the LAGLIDADG and PD-(D/E)XK deoxyribonucleases.
AB  - The tRNA splicing endoribonuclease EndA from Methanococcus jannaschii is a
      homotetramer formed via heterologous interaction between the two pairs of
      homodimers. Each monomer consists of two alpha/beta domains, the N-terminal
      domain (NTD) and the C-terminal domain (CTD) containing the RNase A-like active
      site. Comparison of the EndA coordinates with the publicly available protein
      structure database revealed the similarity of both domains to site-specific
      deoxyribonucleases: the NTD to the LAGLIDADG family and the CTD to the PD-(D/E)XK
      family. Superposition of the NTD on the catalytic domain of LAGLIDADG homing
      endonucleases allowed a suggestion to be made about which amino acid residues of
      the tRNA splicing nuclease might participate in formation of a presumptive
      cryptic deoxyribonuclease active site. On the other hand, the CTD and PD-(D/E)XK
      endonucleases, represented by restriction enzymes and a phage lambda exonuclease,
      were shown to share extensive similarities of the structural framework, to which
      entirely different active sites might be attached in two alternative locations.
      These findings suggest that EndA evolved from a fusion protein with at least two
      distinct endonuclease activities: the ribonuclease, which made it an essential
      "antitoxin" for the cells whose RNA genes were interrupted by introns, and the
      deoxyribonuclease, which provided the means for homing-like mobility. The
      residues of the noncatalytic CTDs from the positions corresponding to the
      catalytic side chains in PD-(D/E)XK deoxyribonucleases map to the surface at the
      opposite side to the tRNA binding site, for which no function has been
      implicated. Many restriction enzymes from the PD-(D/E)XK superfamily might have
      the potential to maintain an additional active or binding site at the face
      opposite the deoxyribonuclease active site, a property that can be utilized in
      protein engineering.

PMID- 11344335
TI  - Entropy-enthalpy compensation: fact or artifact?
AB  - The phenomenon of entropy-enthalpy (S-H) compensation is widely invoked as an
      explanatory principle in thermodynamic analyses of proteins, ligands, and nucleic
      acids. It has been suggested that this compensation is an intrinsic property of
      either complex, fluctuating, or aqueous systems. The questions examined here are
      whether the observed compensation is extra-thermodynamic (i.e., reflects anything
      more than the well-known laws of statistical thermodynamics) and if so, what does
      it reveal about the system? Compensation is rather variably defined in the
      literature and different usages are discussed. The most precise and interesting
      one, which is considered here, is a linear relationship between DeltaH and DeltaS
      for some series of perturbations or changes in experimental variable. Some recent
      thermodynamic data on proteins purporting to show compensation is analyzed and
      shown to be better explained by other causes. A general statistical mechanical
      model of a complex system is analyzed to explore whether and under what
      conditions extra-thermodynamic compensation can occur and what it reveals about
      the system. This model shows that the most likely behavior to be seen is linear S
      H compensation over a rather limited range of perturbations with a compensation
      temperature Tc = dDeltaH/dDeltaS within 20% of the experimental temperature. This
      behavior is insensitive to the details of the model, thus revealing little extra
      thermodynamic or causal information about the system. In addition, it will likely
      be difficult to distinguish this from more trivial forms of compensation in real
      experimental systems.

PMID- 11344336
TI  - Open-and-shut cases in coiled-coil assembly: alpha-sheets and alpha-cylinders.
AB  - The coiled coil is a ubiquitous protein-folding motif. It generally is accepted
      that coiled coils are characterized by sequence patterns known as heptad repeats.
      Such patterns direct the formation and assembly of amphipathic alpha-helices, the
      hydrophobic faces of which interface in a specific manner first proposed by Crick
      and termed "knobs-into-holes packing". We developed software, SOCKET, to
      recognize this packing in protein structures. As expected, in a trawl of the
      protein data bank, we found examples of canonical coiled coils with a single
      contiguous heptad repeat. In addition, we identified structures with multiple,
      overlapping heptad repeats. This observation extends Crick's original postulate:
      Multiple, offset heptad repeats help explain assemblies with more than two
      helices. Indeed, we have found that the sequence offset of the multiple heptad
      repeats is related to the coiled-coil oligomer state. Here we focus on one
      particular sequence motif in which two heptad repeats are offset by two residues.
      This offset sets up two hydrophobic faces separated by approximately 150 degrees 
      160 degrees around the alpha-helix. In turn, two different combinations of these
      faces are possible. Either similar or opposite faces can interface, which leads
      to open or closed multihelix assemblies. Accordingly, we refer to these two forms
      as alpha-sheets and alpha-cylinders. We illustrate these structures with our own
      predictions and by reference to natural variants on these designs that have
      recently come to light.

PMID- 11344337
TI  - Rod and cone degeneration in the rd mouse is p53 independent.
AB  - PURPOSE: To determine whether p53 is required for the death of rod and cone
      photoreceptors in rd mice, a model of human retinitis pigmentosa, and/or for the
      natural degeneration of inner nuclear layer (INL) cells in the developing retina.
      METHODS: Rod photoreceptor and INL apoptosis was assessed by TUNEL staining of
      mouse sagittal sections from post natal day (P) 10, 13, 15, 17, and 20 day p53+/+
      and p53-/- rd retinas. Cone photoreceptor survival was measured by counting the
      total number of peanut agglutinin (PNA) positive cells in eighty four 0.25 mm x
      0.25 mm bins in each eye, distributed equally across the four quadrants of whole
      mount retinas from 3 month old p53+/+ and p53-/- rd retinas. RESULTS: Both the
      kinetics of rod and INL cell death as well as the survival of cones were
      essentially unaffected by the absence of p53. CONCLUSIONS: Despite established
      links with retinal apoptosis, p53 is not essential for rod or cone cell
      degeneration in the rd mouse or for the elimination of bipolar and Muller cells
      during late retinal development.

PMID- 11344338
TI  - MK/T-1, an immortalized fibroblast cell line derived using cultures of mouse
      corneal stroma.
AB  - PURPOSE: Immortalized cell lines representing fibroblast cells from corneal
      stroma would facilitate studies of corneal cell biology and injury response.
      METHODS: Primary cultures of cells derived from mouse corneal stroma were
      transfected with a human telomerase reverse transcriptase (hTERT) expression
      construct to maximize chances of cellular immortalization. A resulting cell line
      was analyzed for telomerase activity, cell growth characteristics, senescence and
      gene expression patterns. Specific responses to transforming growth factor beta
      (TGF-beta) were also analyzed. RESULTS: An immortalized cell line was derived and
      was named MK/T-1. MK/T-1 cells show no signs of cellular senescence or
      transformation at over 100 passages. Telomerase activity was significantly higher
      in MK/T-1 cells as compared to the parental cell cultures. However, relative
      telomere length (RTL) in the MK/T-1 and parental cells was not significantly
      different. Senescence associated beta-galactosidase (SA-beta-Gal) activity was
      not detected in late passage MK/T-1 cells while the parental cells had already
      upregulated SA-beta-Gal at high levels by passage 9. The MK/T-1 cells express
      vimentin, tubulin, lumican, mimecan, decorin and collagen I, but not keratocan.
      Exposure of the MK/T-1 cells to TGF-beta induces the expression of smooth muscle
      alpha-actin (ASMA), the activation of MAP Kinase (p38-MAPK) and morphological
      changes consistent with cytoskeletal reorganization. CONCLUSIONS: MK/T-1 cells
      represent an immortalized fibroblast cell line derived using cultures from
      corneal stroma cell preparations. Expression of hTERT may contribute to
      immortalization of the MK/T-1 cells by a mechanism other than increases in RTL.
      MK/T-1 cells may be a useful model in which to study the responses of corneal
      fibroblast cells to cytokines and other diverse environmental factors in vitro.

PMID- 11344340
TI  - Will genetically modified foods be allergenic?
AB  - Foods produced through agricultural biotechnology, including such staples as
      corn, soybeans, canola, and potatoes, are already reaching the consumer
      marketplace. Agricultural biotechnology offers the promise to produce crops with
      improved agronomic characteristics (eg, insect resistance, herbicide tolerance,
      disease resistance, and climatic tolerance) and enhanced consumer benefits (eg,
      better taste and texture, longer shelf life, and more nutritious). Certainly, the
      products of agricultural biotechnology should be subjected to a careful and
      complete safety assessment before commercialization. Because the genetic
      modification ultimately results in the introduction of new proteins into the food
      plant, the safety, including the potential allergenicity, of the newly introduced
      proteins must be assessed. Although most allergens are proteins, only a few of
      the many proteins found in foods are allergenic under the typical circumstances
      of exposure. The potential allergenicity of the introduced proteins can be
      evaluated by focusing on the source of the gene, the sequence homology of the
      newly introduced protein to known allergens, the expression level of the novel
      protein in the modified crop, the functional classification of the novel protein,
      the reactivity of the novel protein with IgE from the serum of individuals with
      known allergies to the source of the transferred genetic material, and various
      physicochemical properties of the newly introduced protein, such as heat
      stability and digestive stability. Few products of agricultural biotechnology
      (and none of the current products) will involve the transfer of genes from known
      allergenic sources. Applying such criteria provides reasonable assurance that the
      newly introduced protein has limited capability to become an allergen.

PMID- 11344341
TI  - The other side of the coin: the protective role of the TH2 cytokines.
AB  - Although T(H)2 cytokine involvement in allergy makes these cytokines attractive
      therapeutic targets, they protect against ectoparasites and gastrointestinal
      worms and suppress inflammation induced by T(H)1 cytokines. T(H)2 cytokines
      induce mastocytosis, eosinophilia, IgE synthesis, and mucus production. Each
      element of this response protects against some worms; however, different worms
      are protected against by different elements of the total response. The induction
      of the entire response by most parasitic worms suggests that it is safer for the
      immune system to make a stereotyped worm-protective response than to attempt to
      match a more specific response to a particular worm. In contrast, the reciprocal
      antagonism between T(H)1 and T(H)2 cytokines suggests that it is safer for the
      immune system to limit immunopathology by suppressing inflammatory effector
      mechanisms not required for host protection against a particular pathogen class
      than to make an all-purpose inflammatory response. This, in turn, implies that
      innate immunity can distinguish different classes of parasites (eg, worms vs
      protozoa) but has limited ability to distinguish individual parasites within a
      class (eg, different worms). Although these considerations suggest that T(H)2
      cytokine antagonists may increase the risk and severity of worm infections and
      T(H)1 cytokine-mediated inflammatory disorders, such therapy should be relatively
      safe if it is restricted to areas in which worm infections are rare and
      commonsense precautions are taken to minimize the risk of inducing T(H)1 cytokine
      related inflammatory disease.

PMID- 11344342
TI  - Insect sting allergy: the dilemma of the negative skin test reactor.

PMID- 11344343
TI  - Addition of salmeterol to low-dose fluticasone versus higher-dose fluticasone: an
      analysis of asthma exacerbations.
AB  - BACKGROUND: Adding salmeterol to low-dose fluticasone propionate (FP) produces
      greater improvements in pulmonary function and symptom control than increasing
      the dose of FP in patients who remain symptomatic with low-dose FP. OBJECTIVE: We
      sought to compare the rates and characteristics of asthma exacerbations in
      patients after adding salmeterol to low-dose FP with the rates and
      characteristics of exacerbations in patients receiving higher dose FP. METHODS:
      In 2 multicenter, double-blind studies, 925 patients 12 years of age and older
      receiving 88 microg twice daily FP randomly received either 42 microg of
      salmeterol and 88 microg of FP or an increased dose of FP (220 microg) twice
      daily for 24 weeks. Exacerbation rates and clinical measures of asthma worsening
      were assessed for all patients who experienced an asthma exacerbation. RESULTS:
      The addition of salmeterol resulted in a significantly lower rate and number of
      exacerbations compared with higher dose FP. A total of 41 (8.8%) patients
      experienced 47 exacerbations with the addition of salmeterol compared with 63
      (13.8%) patients with 75 exacerbations in the group receiving increased-dose FP
      (P =.017). Salmeterol plus low-dose FP was significantly more protective than
      increased-dose FP in preventing asthma exacerbations, as assessed by the time to
      first exacerbation (P <.05). In both groups clinical indicators of worsening
      asthma showed parallel changes before asthma exacerbation, and greater
      improvements were observed after exacerbation with salmeterol compared with
      higher dose FP. CONCLUSION: Salmeterol plus low-dose FP was more effective than
      higher dose FP alone in reducing asthma exacerbations in patients with persistent
      asthma. The ability to detect deteriorating asthma and the severity of
      exacerbation was similar between groups.

PMID- 11344344
TI  - Metropolitan home living conditions associated with indoor endotoxin levels.
AB  - BACKGROUND: Household endotoxin exposure in allergy and asthma has been gaining
      attention for its dual potential to exacerbate these conditions in individuals
      with established disease and to abrogate atopy before disease onset. OBJECTIVE:
      We sought to better understand the home environmental and lifestyle factors
      influencing house dust endotoxin levels. METHODS: From the homes of 86 infants
      with wheeze in metropolitan Denver, Colorado, house dust endotoxin (detected with
      a standardized Limulus Amebocyte Lysate assay) and common indoor allergen (Fel d
      1, Can f 1, Der p 1, Der f 1, and Bla g 1) contents were quantified.
      Comprehensive home environment and lifestyle questionnaires were completed during
      home visits by trained study staff and parents. RESULTS: House dust endotoxin
      levels were associated with only 2 home environmental features: animals in the
      home and the presence of central air conditioning. The strongest positive
      associations were found with animals in the home. Interestingly, the homes
      without cats or other animals revealed a negative correlation between house dust
      Fel d 1 and endotoxin (P =.03). Central air conditioning, especially during
      months of typical use, was associated with lower house dust endotoxin levels. No
      significant associations between house dust endotoxin levels and home dampness,
      number of household inhabitants or young children, cleaning frequency, or
      presence of tobacco smokers in the home were found. CONCLUSIONS: Indoor endotoxin
      exposure can be increased by the presence of animals in the home and decreased
      with central air conditioning. In some homes without animals, where allergen
      exposure adequate for sensitization still occurs, there are lower levels of house
      dust endotoxin. Therefore in homes without animals, factors that influence
      allergen and endotoxin levels in house dust probably differ. Households with
      detectable allergen levels but low endotoxin levels may provide a predisposing
      environment for animal allergen sensitization.

PMID- 11344345
TI  - Healthy subjects express differences in clinical responses to inhaled
      lipopolysaccharide that are related with inflammation and with atopy.
AB  - BACKGROUND: Endotoxin and its purified derivative LPS are important contaminants
      of both domestic and occupational environments that have been related to airway
      diseases. A body of data suggests that there is considerable interindividual
      variability in LPS sensitivity. OBJECTIVE: The aim of the study was to relate the
      individual clinical responses to inhaled LPS with the inflammatory process and
      the atopic status. METHODS: Fifteen healthy subjects were challenged each week by
      inhalation with saline solution or LPS (0.5, 5, or 50 microg). The systemic
      response was defined by the increase in body temperature, blood neutrophilia,
      acute-phase proteins (C-reactive protein and LPS-binding protein [LBP]), and E
      selectin. The LPS-induced airway response was defined as the increase in airway
      responsiveness and related to the cell count and concentration of TNF-alpha,
      myeloperoxidase, and eosinophil cationic protein in induced sputum. The atopic
      status was defined as an increase in IgE or a positive skin prick test result.
      RESULTS: Subjects (n = 7) with a significant increase in body temperature had a
      larger increase in the systemic inflammatory response (blood neutrophilia; P
      <.01) and in blood concentrations of C-reactive protein (P <.02) and LBP (P
      <.01). Subjects with a significant increase in airway responsiveness (n = 8) had
      an increase in the sputum concentration of eosinophil cationic protein (P <.01).
      The amplitude of the systemic response (increase in body temperature [P <.001],
      blood neutrophilia [P <.02], and rise in LBP [P <.05] and decrease in FEV(1) [P
      <.01]) were inversely associated with the atopic status, suggesting a link
      between atopy and LPS responsiveness. CONCLUSIONS: The clinical response to LPS
      occurs systemically or locally and is associated with inflammation. The atopic
      status was inversely related to the systemic inflammation.

PMID- 11344347
TI  - Eosinophil markers in blood, serum, and urine for monitoring the clinical course
      in childhood asthma: impact of budesonide treatment and withdrawal.
AB  - BACKGROUND: Markers of airway inflammation are needed for prediction of asthma
      deterioration and evaluation of disease severity. Few studies have focused on the
      dynamics of airway inflammation as reflected by the activity of the eosinophils
      and their proteins after withdrawal of inhaled corticosteroids. OBJECTIVE: Our
      goal was to investigate the effect of withdrawal of inhaled budesonide on
      eosinophil count in blood and eosinophil proteins in serum and urine and to
      relate the levels of these markers to the risk of symptoms of asthma, increased
      bronchial hyperresponsiveness, and deterioration of lung function. METHODS:
      Thirty-three children were randomly selected to continue or discontinue use of
      inhaled budesonide in a double-blind, placebo-controlled study. They were
      followed up for 4 months with regular analysis of blood, serum, and urine
      samples; lung function; and methacholine challenges. Eosinophil activity markers
      were analyzed. Age-matched healthy children provided reference data for all
      parameters measured. RESULTS: The eosinophil number in blood and eosinophil
      protein levels in serum (serum eosinophil cationic protein [ECP] and serum
      eosinophil peroxidase [EPO]) increased significantly in the withdrawal group, and
      the difference between the groups was significant (P =.02 for all). Twenty-nine
      percent of the children in the withdrawal group remained symptom free. This
      subgroup had eosinophil counts at baseline below 350/microL, a serum ECP level
      below 15 microg/L, and a serum EPO level below 25 microg/L, each of which was
      related to a low risk of exacerbation (relative risk = 0.37, 0.48, and 0.37
      respectively; P <.05 for all). All eosinophil markers were lower in the healthy
      children than in the symptom-free children with asthma. CONCLUSION: Our data
      indicate that eosinophil count and/or ECP and EPO levels can be used to estimate
      the short-term risk of deterioration and the need for corticosteroid treatment in
      cases of mild and moderate allergic asthma.

PMID- 11344346
TI  - Allergen-induced changes in airway responsiveness are not related to indices of
      airway edema.
AB  - BACKGROUND: The mechanisms behind airway hyperresponsiveness in asthma are
      unknown. Airway wall edema has been proposed as one possible culprit of this
      phenomenon. OBJECTIVE: To test the hypothesis that airway edema may be the cause
      of allergen-induced increases in airway responsiveness in asthma, this trial
      aimed at determining the relationship between allergen-induced changes in airway
      responsiveness to inhaled methacholine and indirect indices of edema, namely
      peripheral airway resistance and the levels of the plasma protein fibrinogen in
      bronchoalveolar lavage (BAL) fluids. METHODS: Twenty-six atopic individuals with
      mild asthma were subjected to bronchoscopy at baseline and 28 hours after
      allergen inhalation. Before each bronchoscopy, methacholine bronchoprovocation
      was performed. During bronchoscopy, peripheral airway resistance measurements
      were obtained by wedged bronchoscopy. BAL fluids were analyzed for fibrinogen, as
      well as for eosinophilic cationic protein. Cytology was performed, and cytokine
      gene expression was assessed with competitive reverse transcriptase PCR from cell
      pellets. RESULTS: A significant increase in airway responsiveness to methacholine
      was recorded after allergen, but this did not correlate with changes in
      peripheral airway resistance (which was not affected) or with BAL fibrinogen
      (which decreased after allergen). Other BAL outcomes confirmed that airway
      inflammation was produced and was characterized by a T(H)2 cytokine pattern.
      CONCLUSIONS: Airway responsiveness in asthma increases after exposure to allergen
      in the absence of increased indirect indices of edema. The role of edema in this
      phenomenon should therefore be tested more vigorously.

PMID- 11344348
TI  - Fifteen-year follow-up of pulmonary function in individuals heterozygous for the
      cystic fibrosis phenylalanine-508 deletion.
AB  - BACKGROUND: In a cross-sectional study, we previously showed that cystic fibrosis
      phenylalanine-508 deletion (DeltaF508) heterozygosity may be overrepresented
      among individuals with asthma. OBJECTIVE: Using 15-year follow-up data from the
      Copenhagen City Heart Study, we now further explore this relationship. METHODS:
      As part of 3 surveys in 1976 to 1978, 1981 to 1983, and 1991 to 1994, we measured
      pulmonary function and asked all participants about asthma and pulmonary risk
      factors. RESULTS: There was no difference in annual decline in lung function
      between DeltaF508 heterozygotes and noncarriers overall; however, among
      individuals with familial asthma, the annual declines in FEV(1) and forced vital
      capacity (FVC) were 49 and 36 mL in DeltaF508 heterozygotes versus 24 and 17 mL
      in noncarriers (P =.01 and P =.12, respectively). Cross-sectionally based on
      triple measurements, FEV(1) and FVC in individuals aged 20 to 70 years were lower
      in heterozygous participants versus noncarriers (P =.02 and P =.004,
      respectively). The average reduction of FEV(1) and FVC in DeltaF508 heterozygotes
      versus noncarriers was 70 mL (P =.06) and 136 mL (P =.008). Finally, 10% of
      carriers reported asthma versus 7% of noncarriers (P =.02), resulting in an odds
      ratio of 2.0 (1.3-3.2) for asthma in DeltaF508 heterozygotes. CONCLUSION: Cystic
      fibrosis DeltaF508 heterozygotes may be overrepresented among individuals with
      asthma and may have poorer lung function than noncarriers. Furthermore, DeltaF508
      heterozygosity in context with familial predisposition to asthma may be
      associated with a greater annual FEV(1) decline.

PMID- 11344349
TI  - Effects of glucocorticoids on endogenous and transcellular metabolism of
      eicosanoids in asthma.
AB  - BACKGROUND: Human blood polymorphonuclear cells, which biosynthesize eicosanoids
      from the 5-lipoxygenase (5-LO) pathway, are likely to be involved in asthma, in
      which glucocorticoids represent the first line of therapy. Their effects on
      leukotriene release after a short course of treatment, which have been reported
      in several studies, are controversial. OBJECTIVE: We sought to investigate
      whether long-term oral glucocorticoids inhibit lipid mediators from the 5-LO
      pathway. METHODS: Twelve normal control subjects, 29 asthmatic subjects, and 50
      glucocorticoid-dependent asthmatic subjects were included in the study.
      Polymorphonuclear cells were studied for endogenous and transcellular metabolism
      of eicosanoids. RESULTS: Total leukotriene B(4) production was significantly
      lower in cells from glucocorticoid-dependent asthmatic subjects (mean +/- SD, 177
      +/- 26 ng/10(7) cells) than in control subjects (406 +/- 27), untreated asthmatic
      subjects (421 +/- 34), and asthmatic subjects treated with inhaled
      glucocorticoids (290 +/- 56). When incubated with arachidonic acid, these
      polymorphonuclear cells released very low amounts of 5(S)- and 12(S)-hydroxy
      eicosatetraenoic acid (HETE), whereas endogenous 15(S)-HETE was found in
      substantial amounts. The transformation of exogenous 15(S)-HETE into 5(S),15(S)
      diHETE and lipoxins was significantly more important in untreated asthmatic
      subjects than in control subjects and glucocorticoid-dependent asthmatic
      subjects. CONCLUSION: This study showed that long-term oral corticotherapy
      affects the 5-LO activity and leads to a decrease production of all metabolites
      in contrast to short-term or inhaled glucocorticoids. This study also questions
      the site of action of glucocorticoids in regulating the availability of
      arachidonic acid and potential eicosanoid regulation, as previously held in
      phospholipase A2 studies.

PMID- 11344350
TI  - Expression and modulation of FcepsilonRIalpha and FcepsilonRIbeta in human blood
      basophils.
AB  - BACKGROUND: The IgE receptor (FcepsilonRI) may exist as a tetramer
      (alphabetagamma2) or a trimer (alphagamma2) because FcepsilonRIbeta is
      dispensable for membrane expression of FcepsilonRIalpha. FcepsilonRIbeta
      amplifies signaling of FcepsilonRI so that regulation of FcepsilonRIalpha:beta
      stoichiometry would affect cellular responsiveness. OBJECTIVE: We examined
      basophils from a variety of donors for differences in their expression of
      FcepsilonRIalpha and FcepsilonRIbeta protein. METHODS: Enriched blood basophils
      were assessed at baseline and after IL-3 culture for FcepsilonRIalpha and
      FcepsilonRIbeta protein by Western blotting, surface FcepsilonRIalpha by flow
      cytometry, and FcepsilonRIbeta mRNA by real-time PCR. Basophil functional
      response was measured by allergen-triggered histamine release. RESULTS: For the
      FcepsilonRIalpha subunit, 2 protein bands with molecular weights of 50 kd and 60
      kd were identified by Western blots. The 60-kd band correlated to surface
      expressed FcepsilonRIalpha detected by flow cytometry (Spearman R = 0.78, P
      <.01). Surface FcepsilonRIalpha also correlated with FcepsilonRIbeta protein
      (Spearman R = 0.92, P <.01). FcepsilonRIbeta protein levels increased
      disproportionately with higher surface FcepsilonRIalpha expression. The ratio of
      FcepsilonRIbeta to FcepsilonRIalpha varied 10-fold among donors and correlated
      with surface FcepsilonRIalpha. Basophil 50-kd alpha protein levels were similar
      despite a 10-fold range in surface FcepsilonRIalpha expression, implying stores
      of this protein such as those found in eosinophils. Unlike eosinophils, the
      basophil 50-kd protein was lost with culture and was absent from supernatants.
      Levels of beta protein and mRNA were enhanced by IL-3 culture, whereas
      FcepsilonRIalpha expression (by flow cytometry and 60 kd) was not. CONCLUSION:
      These findings demonstrate variable stoichiometry of FcepsilonRIalpha:beta in
      whole cells and that this stoichiometry can be altered by IL-3 culture. With the
      assumption that all detected beta protein is surface expressed, these findings
      suggest a variable stoichiometry for FcepsilonRIalpha:beta that is also related
      to FcepsilonRIalpha surface expression.

PMID- 11344351
TI  - Mass, charge, and subcellular localization of a unique secretory product
      identified by the basophil-specific antibody BB1.
AB  - BACKGROUND: BB1 is a basophil-specific mAb (Lab Invest 1999;79:27-38). The
      identity of the corresponding antigen has not been determined, but it gives a
      granular appearance on staining and is secreted on activation of basophils.
      OBJECTIVE: We sought to further characterize the basophilspecific antigen
      identified by BB1. METHODS: Intracellular localization was determined by flow
      cytometry and by immunogold labeling and electron microscopy. Physical chemical
      properties were investigated by gel filtration chromatography and preparative
      isoelectric focusing. RESULTS: In flow cytometry, permeabilization of cells
      increased immunofluorescence 100-fold, confirming the predominantly intracellular
      localization of the antigen. It was further localized to the secretory granules
      by immunoelectron microscopy. Double labeling with a CD63-specific antibody
      demonstrated selective binding of BB1 to the granule matrix. Gel filtration
      chromatography indicated that the antigen is secreted as a complex of
      approximately 5 x 10(6) d, which was well resolved from the 210-kd supramolecular
      complex containing tryptase. The antigen was degraded by pronase. Isoelectric
      focusing indicated a highly basic protein with an isoelectric point of 9.6.
      CONCLUSION: With its granule localization, release on cell activation, and unique
      properties, the antigen identified by BB1 could be a novel mediator of allergic
      disease. We propose the name basogranulin for this novel basophil-specific
      protein.

PMID- 11344353
TI  - Group 13 grass allergens: structural variability between different grass species
      and analysis of proteolytic stability.
AB  - BACKGROUND: Determination of the allergen composition of an extract is essential
      for the improvement of hyposensitization therapy. Surprisingly, although grass
      pollen extracts have been studied intensively for 20 years, a further major
      allergen, Phl p 13, was detected recently in timothy grass pollen. OBJECTIVES: We
      sought to determine the occurrence and importance of group 13 allergens in
      various grass species and to investigate their proteolytic stability. METHODS:
      The group 13 allergens were determined by means of 2-dimensional PAGE blotting
      with patient sera and group 13-specific mAbs. The allergens were isolated
      chromatographically from several pollen extracts and analyzed by means of
      microsequencing. Cross-reactivity among various grass species was studied by
      using Western blots and immunoblot inhibition tests. The stability of the
      allergens was tested under defined extraction conditions. RESULTS: Group 13
      allergens are detectable in all common grasses and show IgE cross-reactivity
      among them. The allergenic components were identified in the neutral pH range
      with molecular masses of 50 to 60 kd, and in the case of Phl p 13, maximal
      binding of the isoforms was observed at 55 kd and at an isoelectric point of 6 to
      7.5. Protein sequencing clearly confirms structural identities between different
      grass species, although individual variations are found. If low-molecular-mass
      components were depleted by means of gel filtration, a rapid degradation of group
      13 allergens was observed. This is in contrast to other pollen allergens
      described thus far. CONCLUSION: Group 13 allergens are widespread and are major
      allergens in the grasses. Predicted from their primary structures, these
      allergens are polygalacturonases. This class of enzymes is already known from
      microorganisms, and these enzymes are recognized as potential inducers of asthma.
      Our studies indicate that the group 13 allergens show a considerable
      microheterogeneity and degradation, especially after depletion of low-molecular
      mass components. One has to be aware of this pivotal fact when soluble grass
      pollen extracts are prepared for diagnostics and hyposensitization therapy.

PMID- 11344352
TI  - Effects of purine and pyrimidine nucleotides on intracellular Ca2+ in human
      eosinophils: activation of purinergic P2Y receptors.
AB  - BACKGROUND: Extracellular adenosine 5'-triphosphate (ATP) increases human
      eosinophil intracellular Ca(2+) concentration; the mechanism of action is not
      fully known. ATP, a physiologic regulator, acts through 2 purinergic receptor
      types: cation channels (P2X) and G protein-coupled receptors (P2Y). OBJECTIVE:
      This study is aimed at identifying the functional purinergic receptors in human
      eosinophils. METHODS: The relative potency of ATP, uridine (UTP), cytidine (CTP),
      and inosine (ITP) 5'-triphosphates (P2Y agonists); 2-methylthio-ATP (P2Y(1)
      agonist); and 2 P2X agonists, alpha,beta-methylene-ATP and beta,gamma-methylene
      ATP on intracellular Ca(2+) concentration was examined in Ca(2+)-sensitive Fura-2
      labeled human eosinophils. For comparison, ATP effects were similarly studied in
      human neutrophils. P2X/P2Y mRNA expression in cells was examined by reverse
      transcription and PCR. RESULTS: The nucleotide potency order was UTP > or = ATP >
      ITP >>> 2-methylthio-ATP > alpha,beta-methylene-ATP = beta,gamma-methylene-ATP =
      CTP = 0 in eosinophils. Pertussis toxin (500 ng/mL) pretreatment abolished the
      effect of lower (10(-6) mol/L) but not higher (10(-5) mol/L) concentrations of
      ATP in eosinophils, whereas it attenuated the effects of 10(-4) mol/L ATP in
      neutrophils. The phospholipase C inhibitor U73122 (2 micromol/L) partially
      inhibited the effect of ATP in eosinophils but totally blocked it in neutrophils.
      Both cells constitutively express mRNA for P2X(1), P2X(4), P2X(5), P2Y(1), and
      P2Y(2), but not P2X(7), with much weaker expressions of P2X(4) and P2X(5) in
      neutrophils. Eosinophils cultured with the T(H)1 cytokine, IFN-gamma, expressed
      mRNA for P2X(7), a receptor linked to apoptosis. CONCLUSIONS: These results
      suggest that the P2 purinergic receptor signal transduction pathways in
      eosinophils and neutrophils are different and are mediated by more than 1 subtype
      of functional P2Y receptors.

PMID- 11344354
TI  - Normally suppressing CD40 coregulatory signals delivered by airway macrophages to
      TH2 lymphocytes are defective in patients with atopic asthma.
AB  - BACKGROUND: We have previously shown that airway macrophages (AMs) from atopic
      nonasthmatic subjects, but not atopic asthmatic subjects, inhibit T-cell IL-5
      production during an allergen-dependent interaction. However, the mechanisms
      responsible for the IL-5-modulating effect of the AMs are less clear. OBJECTIVES:
      The aim of the present study was to define the roles of B7 and CD40 costimulatory
      signals delivered by AMs in regulating T-cell IL-5 responses in an allergen
      stimulated coculture system. METHODS: Peripheral blood CD4(+) T cells and AMs
      were cocultured under different conditions. RESULTS: Compared with those from
      well-matched atopic nonasthmatic subjects, AMs from atopic asthmatic subjects
      demonstrated a significantly lower expression of B7-1 and CD40, but not B7-2 and
      HLA-DR, after either fresh isolation or coculture with allergen-reactive CD4(+) T
      cells. Lower IL-12 production by the AMs from asthmatic subjects was also
      observed under the same conditions. Allergen-related T-cell IFN-gamma and IL-5
      production was inhibited by the addition of either neutralizing B7-1 or B7-2
      antibody to the cocultures in both atopic groups. In contrast, IL-5 production
      was significantly increased by the addition of blocking CD40 antibody, whereas IL
      12 production by the AMs was inhibited. Anti-IL-12 mAb enhanced IL-5 production
      in the cocultures from atopic nonasthmatic subjects, whereas a dose-dependent
      suppressive effect of recombinant human IL-12 on IL-5 production was seen in
      atopic asthmatic subjects. CONCLUSION: In this coculture model system, lower IL
      12 production by AMs and higher IL-5 production by CD4(+) T cells in atopic
      asthmatic subjects compared with that found in atopic nonasthmatic subjects are
      related to the lower expression of CD40 rather than B7-1 signals on the AMs from
      these patients.

PMID- 11344355
TI  - Keratinocytes from patients with atopic dermatitis and psoriasis show a distinct
      chemokine production profile in response to T cell-derived cytokines.
AB  - BACKGROUND: Atopic dermatitis (AD) and psoriasis are genetically determined
      inflammatory skin disorders. Keratinocytes actively participate in cutaneous
      inflammatory responses by elaborating various chemokines. OBJECTIVE: We
      investigated the capacity of IL-4, IFN-gamma, and TNF-alpha to modulate the
      expression of CCL and CXCL chemokines in cultured keratinocytes from patients and
      healthy individuals, as well as chemokine expression in situ. METHODS:
      Keratinocyte cultures were established from normal-looking skin of adult patients
      with AD or psoriasis vulgaris and from healthy subjects. Monocyte chemoattractant
      protein 1 (MCP-1)/CCL2, RANTES/CCL5, IL-8/CXCL8, and IFN-gamma-induced protein of
      10 kd (IP-10)/CXCL10 production was evaluated at the mRNA and protein levels by
      using RNase protection assay and ELISA, respectively. The expression of the same
      chemokines was studied in chronic lesional skin by means of immunohistochemistry
      or in situ hybridization. RESULTS: Only IL-8 mRNA was detected in unstimulated ke
      ratinocyte cultures. MCP-1 and IP-10 were potently induced by IFN-gamma, whereas
      IL-8 and RANTES were preferentially upregulated by TNF-alpha and, to a lesser
      extent, by IFN-gamma. IL-4 weakly induced IP-10, RANTES, and IL-8 but not MCP-1.
      Keratinocytes of patients with AD invariably responded with significantly earlier
      and higher RANTES expression. By contrast, keratinocytes of patients with
      psoriasis displayed much higher levels of both constitutive and induced IL-8 and
      a stronger induction of MCP-1 and IP-10. RANTES and MCP-1 mRNA(+) keratinocytes
      were detected in the basal layer of lesions of patients with AD and psoriasis. IP
      10 and IL-8 were consistently upregulated in the epidermis of patients with
      psoriasis but not in lesions of patients with AD. CONCLUSIONS: Keratinocytes of
      patients with AD and psoriasis show an intrinsically abnormal and different
      chemokine production profile and may thus favor the recruitment of distinct
      leukocyte subsets into the skin.

PMID- 11344356
TI  - Perforin hyperreleasability and depletion in cytotoxic T cells from patients with
      exacerbated atopic dermatitis and asymptomatic rhinoconjunctivitis allergica.
AB  - BACKGROUND: As a plasma membrane pore-forming protein, perforin is essential for
      T-cell cytotoxicity mediated by lytic granules. Recent studies on the immune
      system of perforin knockout mice demonstrated striking similarities to the
      immunopathology of atopic diseases. OBJECTIVE: We sought to investigate the
      perforin system of atopic patients. METHODS: Monoclonal antibodies were used to
      characterize perforin-positive PBMCs of patients with exacerbated atopic
      dermatitis (AD) and asymptomatic rhinoconjunctivitis allergica (RCA) by means of
      immunoflow cytometry. In addition, a perforin release assay was developed to
      quantify the velocity of ionomycin and phorbol 12-myristate 13-acetate-induced
      secretion of lytic granules. RESULTS: In atopic patients significantly fewer
      lymphocytes contained perforin-positive lytic granules compared with those of
      healthy control subjects (patients with AD: 14% +/- 5%, n = 13, P <.0001;
      patients with RCA: 24% +/- 5%, n = 9, P <.01; healthy control subjects: 33% +/-
      11%, n = 13). Of all CD8(hi+) cytotoxic T lymphocytes (CTLs), only 18% +/- 9% and
      17% +/- 12% were perforin-positive in patients with AD and RCA, respectively,
      compared with 44% +/- 13% in control subjects (P <.0001). In addition, perforin
      positive CD8(hi+) CTLs of atopic patients released their perforin twice as fast
      and more completely than control CTLs. This means that 50% of initially perforin
      positive CD8(hi+) CTLs from patients with AD and RCA released their perforin
      completely within 32 +/- 16 and 36 +/- 19 minutes, respectively, and an over 85%
      release was reached within 113 +/- 41 and 118 +/- 60 minutes, respectively. In
      CTLs of healthy control subjects, however, it took 64 +/- 40 minutes to achieve a
      50% release of lytic granules, and an 85% depletion was not reached in 60% of
      healthy control subjects, even after 180 minutes. CONCLUSION: The perforin
      hyperreleasability explains, at least in part, the decreased percentage of
      perforin-positive CD8(hi+) CTLs in atopic patients. These distortions in the
      system of lytic granules of atopic patients may contribute to the functional
      defects observed in T-cell cytotoxicity in vivo and in vitro in patients with AD
      and RCA.

PMID- 11344357
TI  - Idiopathic environmental intolerance: increased prevalence of panic disorder
      associated cholecystokinin B receptor allele 7.
AB  - BACKGROUND: A growing body of evidence suggests that idiopathic environmental
      intolerance (IEI) is a psychophysiologic disorder with prominent features of
      anxiety/panic and somatization, although proponents of a toxicogenic explanation
      claim, despite a lack of convincing evidence, that symptoms arise from exposure
      to otherwise nonnoxious environmental agents. Patient behaviour is characterized
      by strenuous avoidance of perceived triggers to the point of severe impairment of
      normal social and vocational functioning. IEI proponents claim that previous
      studies showing a high prevalence of psychopathology in patients with IEI and
      studies showing panic responses to known panicogenic challenges merely reflect
      the anxiety-producing result of living with IEI. OBJECTIVE: We explored whether
      IEI and panic disorder, personality traits, or both shared an underlying
      neurogenetic basis that would predate the anxiety of IEI symptomatology. The DNA
      of patients with IEI was examined for the presence of known panic disorder
      associated cholecystokinin B (CCK-B) receptor alleles and for personality trait
      associated dopamine D4 receptor polymorphisms. METHODS: Eleven patients with
      typical IEI symptoms were recruited and were individually matched to normal
      control subjects from an existing bank for age, sex, and ethnic background.
      Genomic DNA was extracted from peripheral blood samples. CCK-B and dopamine D4
      receptor polymorphisms were examined by using standard PCR-based techniques.
      RESULTS: There was a significantly higher prevalence of the panic disorder
      associated CCK-B receptor allele 7 in subjects with IEI (9/22 [40.9%]) compared
      with control subjects (2/22 [9.1%], P =.037). There was no difference in
      personality trait-associated polymorphisms of the gene encoding dopamine D4
      receptor between patients and control subjects. CONCLUSIONS: These findings
      provide preliminary evidence that IEI and panic disorder share a common
      neurogenetic basis, which would predate the anxiety-producing effects of IEI
      symptoms. Further studies with larger samples are warranted, but these results
      support previous studies that suggest that panic disorder may account for much of
      the symptomatology in at least some cases of IEI and provide a basis for rational
      treatment strategies.

PMID- 11344358
TI  - Utility of food-specific IgE concentrations in predicting symptomatic food
      allergy.
AB  - BACKGROUND: The double-blind, placebo-controlled food challenge is considered the
      gold standard for diagnosing food allergy. However, in a retrospective analysis
      of children and adolescents with atopic dermatitis and food allergy, discrete
      food-specific IgE concentrations were established that could predict clinical
      reactivity to egg, milk, peanut, and fish with greater than 95% certainty.
      OBJECTIVE: The purpose of this investigation was to determine the utility of
      these 95% predictive decision points in a prospective evaluation of food allergy.
      METHODS: Sera from 100 consecutive children and adolescents referred for
      evaluation of food allergy were analyzed for specific IgE antibodies to egg,
      milk, peanut, soy, wheat, and fish by using the Pharmacia CAP System FEIA. Food
      specific IgE values were compared with history and the results of skin prick
      tests and food challenges to determine the efficacy of previously established 95%
      predictive decision points in identifying patients with increased probability of
      reacting during a specific food challenge. RESULTS: One hundred children (62%
      male; median age, 3.8 years; range, 0.4-14.3 years) were evaluated for food
      allergy. The diagnosis of food allergy was established by means of history or
      oral food challenge. On the basis of the previously established 95% predictive
      decision points for egg, milk, peanut, and fish allergy, greater than 95% of food
      allergies diagnosed in this prospective study were correctly identified by
      quantifying serum food-specific IgE concentrations. CONCLUSION: In a prospective
      study of children and adolescents referred for evaluation of food allergy,
      previously established 95% predictive decision points of food-specific IgE
      antibody concentrations for 4 major food allergens were effective in predicting
      clinical reactivity. Quantification of food-specific IgE is a useful test for
      diagnosing symptomatic allergy to egg, milk, peanut, and fish in the pediatric
      population and could eliminate the need to perform double-blind, placebo
      controlled food challenges in a significant number of children.

PMID- 11344359
TI  - Insect sting allergy with negative venom skin test responses.
AB  - BACKGROUND: In our 1976 controlled venom immuno rapy trial, 33% of 182 patients
      with a history of systemic reactions to insect stings were excluded because of
      negative venom skin test responses. There have been reports of patients with
      negative skin test responses who have had severe reactions to subsequent stings.
      OBJECTIVE: Our aim is to increase awareness about the patient with a negative
      skin test response and insect sting allergy and to determine the frequency and
      significance of negative skin test responses in patients with a history of
      systemic reactions to insect stings. METHODS: We prospectively examined the
      prevalence of negative venom skin test responses in patients with a history of
      systemic reactions to stings. In patients who gave informed consent, we analyzed
      the outcome of retesting and sting challenge. RESULTS: Of 307 patients with
      positive histories screened for our sting challenge study, 208 (68%) had positive
      venom skin test responses (up to 1 microg/mL concentration), and 99 (32%) had
      negative venom skin test responses. In 36 (36%) of the 99 patients with negative
      skin test responses, the venom RAST result was a low positive (1-3 ng/mL), or
      repeat venom skin test responses were positive; another 7 (7%) patients had high
      venom-specific IgE antibody levels (4-243 ng/mL). Notably, 56 (57%) of 99
      patients with positive histories and negative skin test responses had negative
      RAST results. In patients with positive skin test responses, sting challenges
      were performed in 141 of 196 patients, with 30 systemic reactions. Sting
      challenges were performed on 37 of 43 patients with negative skin test responses
      and positive venom-specific IgE and in 14 of 56 patients with negative skin test
      responses and negative RAST results. There were 11 patients with negative skin
      test responses who had systemic reactions to the challenge sting: 2 had negative
      RAST results, and 9 had positive RAST results at 1 ng/mL. The frequency of
      systemic reaction was 21% in patients with positive skin test responses and 22%
      in patients with negative skin test responses (24% in those with positive RAST
      results and 14% in those with negative RAST results). CONCLUSIONS: Venom skin
      test responses can be negative in patients who will subsequently experience
      another systemic sting reaction. Venom skin test responses are negative in many
      patients with a history of systemic allergic reactions to insect stings and may
      be associated with positive serologic test responses for venom-specific IgE
      antibodies (sometimes strongly positive results). Venom skin test responses
      should be repeated when negative, along with a serologic IgE antivenom test.
      Better diagnostic skin test reagents are urgently needed.

PMID- 11344360
TI  - Maintenance venom immunotherapy administered at 3-month intervals is both safe
      and efficacious.
AB  - BACKGROUND: Maintenance venom immunotherapy (MVIT) is usually administered to
      patients with venom allergy at 4- to 6-week intervals for at least 3 to 5 years.
      The small number of studies assessing the possibility of extending the
      maintenance interval (MI) included either too small a population and patients
      with only vespid and not bee venom (BV) allergy or relied on reaction to field
      stings only. OBJECTIVE: We sought to assess the safety and efficacy of MVIT given
      at 3-month intervals to a large population of patients allergic to both yellow
      jacket venom and BV. METHODS: In all patients undergoing venom immunotherapy, MI
      was gradually extended to 3 months. Systemic reactions (SRs) to immunotherapy
      injections or to field stings were regularly recorded. Some of the patients were
      also deliberately sting challenged during the 3-month interval. Patients
      discontinuing MVIT were interviewed regarding their responses to field re-stings,
      and in some of them, an in-hospital sting challenge was performed. RESULTS: One
      hundred sixty patients mostly allergic to BV were enrolled in the study. Failure
      to reach the 3-month interval was observed in 6 (3.8%) patients, originating in
      failure to reach the full maintenance dose in most of them. SRs to MVIT
      administered at 3-month intervals were observed in 2.6% of the patients. One of
      36 patients who experienced a field sting during the 3-month interval had an
      objective mild SR (2.8%). Two (4.5%) of 44 patients who were deliberately stung
      during the 3-month interval had mild SRs. After discontinuation of MVIT, 2 (8.3%)
      of 24 patients who experienced a field sting had an SR. Both were allergic to
      yellow jacket venom. Three to 82 months after discontinuation of MVIT, 22
      patients allergic to BV were sting challenged. Only one (4.5%) patient had a mild
      objective SR. CONCLUSIONS: The conventional 4- to 6-week MI can easily be
      extended to 3 months in most patients without any adverse events. MVIT given at a
      3-month interval is safe and effective while being administered, as well as after
      its discontinuation. This fact should be applied to almost every patient allergic
      to insect venom.

PMID- 11344361
TI  - Identification of wheat flour allergens by means of 2-dimensional immunoblotting.
AB  - BACKGROUND: Wheat flour proteins are allergens for 60% to 70% of bakers with
      workplace-related respiratory symptoms. OBJECTIVE: The aim of the study was to
      investigate the variability of IgE antibody patterns of wheat flour-sensitized
      bakers and to identify the most frequently recognized allergens. METHODS:
      Water/salt-soluble wheat flour proteins from the cultivar Bussard were separated
      by using 2-dimensional gel electrophoresis with immobilized pH gradients. IgE
      reactive proteins were identified by means of immunoblotting with sera of 10
      subjects with baker's asthma. Mass spectrometric fingerprinting was used to
      identify the proteins most frequently recognized by IgE. RESULTS: The IgE
      immunoblots obtained with 10 different sera exhibited a remarkable heterogeneity.
      Each patient showed an individual IgE-binding pattern with 4 to 50 different
      allergen spots. Altogether, more than 100 IgE-binding protein spots were
      detected. Nine of the predominant IgE-binding protein spots were identified by
      using mass spectrometric fingerprinting. The obtained masses matched 2 different
      isoforms of glycerinaldehyde-3-phosphate dehydrogenase from Hordeum vulgare,
      triosephosphate isomerase from H vulgare, and serpin, a serine proteinase
      inhibitor from Triticum aestivum. CONCLUSIONS: The results show a great
      interindividual variation of IgE-binding patterns of wheat flour proteins in
      baker's asthma. The clinical relevance of the identified 4 new allergens will be
      further investigated in the near future.

PMID- 11344362
TI  - Api m 6: a new bee venom allergen.
AB  - BACKGROUND: Characterization of the primary structure of allergens is a
      prerequisite for the design of new diagnostic and therapeutic tools for allergic
      diseases. OBJECTIVE: The purpose of this study was the identification and
      characterization of a low-molecular-weight, IgE-binding, bee venom (BV) allergen.
      METHODS: BV proteins were separated by using size exclusion chromatography and
      HPLC. IgE antibody binding to purified proteins was analyzed by means of
      immunoblotting, and T-cell response was analyzed by means of proliferation assay.
      Amino acid sequence was determined with 2 approaches, namely Edman degradation
      and carboxy terminal analysis with mass spectrometry. RESULTS: Api m 6, which
      migrated as an 8-kd band in SDS-PAGE, was frequently (42%) recognized by IgE from
      BV-hypersensitive patients. In addition, PBMCs from BV-hypersensitive patients,
      as well as from a normal control subject, proliferated in response to this
      allergen. Api m 6 exists as 4 isoforms of 7190, 7400, 7598, and 7808 d,
      respectively. Amino acid sequences obtained from HPLC-purified preparations
      revealed that the isoforms were constituted of a common central core of 67
      residues, only differing in the amino- and carboxy-terminal ends. Api m 6 showed
      no significant sequence homology with known proteins. CONCLUSIONS: We have
      identified and sequenced a new BV allergen that elicits a strong IgE and T-cell
      response in a large number of BV-hypersensitive patients. Api m 6 should be
      considered in the diagnostic and therapeutic approach of BV immunotherapy on the
      basis of peptides or recombinant proteins.

PMID- 11344363
TI  - Incidence of sensitization, symptoms, and probable occupational
      rhinoconjunctivitis and asthma in apprentices starting exposure to latex.
AB  - Latex is a well-known sensitizer. Prospective studies in apprentices beginning to
      be exposed to latex have not been carried out. We wanted to determine the
      incidence of skin reactivity, cutaneous symptoms, rhinoconjunctivitis (RC)
      symptoms, respiratory symptoms, probable occupational RC, and asthma in
      apprentices in dental hygiene. A total of 122 students starting a program in
      dental hygiene technology were recruited between 1993 and 1995. A questionnaire,
      skin-prick tests with common aeroallergens and latex, and assessment of
      spirometry and responsiveness to methacholine were carried out on entry and at
      follow-up visits at 20 and 32 months after the start of exposure. Of the 110
      subjects who participated for at least 1 follow-up visit, skin reactivity to
      latex developed in 7. Cutaneous symptoms developed in 6 of the 7, RC symptoms
      developed in 2, and respiratory symptoms developed in 1. Five of the 7 subjects
      had significant changes in methacholine responsiveness and fulfilled the
      definition of probable occupational asthma. Sensitized subjects were more likely
      to be atopic and to have a previous history of asthma and respiratory symptoms on
      exercise than were nonsensitized subjects. Three subjects at the 20-month
      assessment and 4 subjects at the 32-month visit showed skin reactivity. The
      cumulative incidences for skin sensitization, probable occupational RC, and
      occupational asthma to latex were 6.4%, 1.8%, and 4.5%, respectively.

PMID- 11344364
TI  - Successful treatment of eosinophilic gastroenteritis with suplatast tosilate.

PMID- 11344365
TI  - Insect sting fatality 9 years after venom treatment (venom allergy, fatality).

PMID- 11344366
TI  - Fatal insect allergy after discontinuation of venom immunotherapy.

PMID- 11344367
TI  - Esophageal leiomyoma incidentally recognized during an acute attack of hereditary
      angioneurotic edema.

PMID- 11344368
TI  - Ferret allergy.

PMID- 11344369
TI  - Ultrarush immunotherapy in patients with Hymenoptera venom allergy.

PMID- 11344373
TI  - Understanding the economic burden of asthma.
AB  - The economic impact of asthma is large and growing, and the use of economic
      outcomes is increasing. Such outcomes serve as the basis for studies of the
      efficiency of care and are being reported increasingly as outcomes of clinical
      trials. This article presents the basic components of a cost-of-illness study,
      the in-fluences that have an impact on these components, the relation of economic
      indicators to clinical outcomes, and the relative importance of the economic
      factors for differing groups in society.

PMID- 11344374
TI  - Links between pediatric and adult asthma.
AB  - Connections between events occurring in early life with adult asthma suggest that
      both the altered regulation of airway caliber and tone and the changes in airway
      structure present in many asthma cases may have their roots in developmental
      patterns established during infancy and childhood. The Melbourne epidemiologic
      study, the British 1958 birth cohort, and the Tasmanian asthma survey all provide
      important information on the outcomes of childhood asthma in later life. Among
      the findings, these studies showed that in a large proportion of asthmatic
      children, asthma remits in early adulthood, and the severity of asthma tracks
      significantly with age. Newer longitudinal studies have measured lung function
      shortly after birth, before any respiratory symptoms have occurred. Several lines
      of evidence suggest that those children who will go on to have more severe and
      persistent asthma symptoms already have immune responses skewed toward the T
      helper type 2 (TH2) at the time of the very first episodes of airway obstruction
      in infancy. In most children whose asthma is triggered mainly by respiratory
      infections, asthma symptoms appear to remit by the adolescent years. Congenital
      and acquired deficits in lung function, however, may lead to recurrence of these
      symptoms during adult life and after long periods of remission, especially among
      active smokers.

PMID- 11344375
TI  - Challenges in assessing outcomes for pediatric asthma.
AB  - Although progress has been made in understanding asthma, much remains unknown; as
      a result, diagnosis and treatment are not optimal. Information is still needed
      about the natural history of asthma to better understand which patients are at
      risk of inflammation and at what point during their disease that inflammation
      occurs. In the case of children, a greater understanding of the disease's natural
      history is needed to establish criteria for early diagnosis and to evaluate
      progressive aspects of the disease so that appropriate measures of progression
      can be defined. The safety of various medications used as long-term controllers
      must also be evaluated. The growing information about medication effects on
      asthma provides unique opportunities to design studies that will guide
      improvement in asthma care. A number of disease outcomes can be used as surrogate
      markers of clinically significant endpoints, and a number of adverse effects may
      serve as surrogate markers. The consequences of poor control of pediatric asthma
      can be observed in a variety of clinical markers, including clinical features of
      the disease that worsen as it progresses, pulmonary function deterioration, lung
      hyperexpansion, and inflammation increases. The Childhood Asthma Management
      Program is an ongoing clinical trial designed to improve the diagnosis and
      treatment of asthma in children. Its hypothesis is that anti-inflammatory
      treatment of childhood asthma will not only relieve morbidity but will also
      improve lung growth.

PMID- 11344377
TI  - Assessment of health status and quality of life outcomes for children with
      asthma.
AB  - Increasing interest has been directed to understanding health outcomes associated
      with pediatric disease processes, including asthma. Salient areas of interest to
      health outcomes research include the child's and parent's subjective experience
      with the disease, a concept most often identified as quality of life. Quality of
      life reports fit within a broader scope of outcome measures embodied in the
      concept of children's health status. This article provides a description for how
      a child's health status can be understood theoretically, from a research
      perspective and in clinical practice. Emphasis is directed to how information
      obtained from both the child and parent is critical to outcomes research and
      clinical practice. Unique methodologic problems in assessing child health
      outcomes such as the challenge of understanding how the child's changing
      cognitive development may have an impact on responses to outcome measures and the
      role of contextual variables such as family characteristics are discussed. A
      variety of subjective and objective outcome measures currently exist that may be
      used in research on children with asthma. Practical guidelines for implementing
      outcomes research for children with asthma are presented. Clinical researchers
      must use multiple outcome measures for assessing asthma characteristics,
      including psychosocial characteristics, which have an impact on adherence and
      treatment regimens.

PMID- 11344376
TI  - Pediatric asthma assessment: validation of 2 symptom diaries.
AB  - Accurate assessment of the value of asthma interventions in pediatric clinical
      trials is an essential step toward the improvement of the treatment of this
      disorder in children. Conventional pulmonary function measures can be infeasible
      and unreliable in younger children, particularly for use in multisite studies. As
      an alternative or supplemental approach, diary questionnaires completed by the
      patients or their caregivers may provide valuable data regarding the efficacy of
      asthma interventions in pediatric clinical trials. These questionnaires, however,
      have routinely not been validated for use in pediatric populations. Two pediatric
      diary questionnaires (the child-completed Pediatric Asthma Diary [PAD] and the
      parent/caregiver-completed Pediatric Asthma Caregiver Diary [PACD]) were designed
      to evaluate asthma symptoms in children aged 6 to 14 years and 2 to 5 years,
      respectively. The validity of these diary questionnaires was evaluated in 2
      separate prospective studies that included children who were divided into 2
      asthma groups: stable (requiring no additional asthma medication) and unstable
      (requiring either an increase in or the addition of asthma medication). Both
      scales displayed significant discriminant validity, construct validity, and
      responsiveness to change in asthma therapy. Only the PACD detected differences
      between groups in nighttime symptoms, such as awakenings caused by asthma. These
      validity studies suggest that diary questionnaires such as the PAD and PACD can
      be valuable as an alternative for the evaluation of interventions in pediatric
      asthma when pulmonary function testing is inappropriate or as an adjunct to such
      objective measures.

PMID- 11344378
TI  - Barriers to measuring and achieving optimal outcomes in pediatric asthma.
AB  - To measure the effectiveness of any therapeutic endeavor, a set of defined
      outcome measurements must be performed, or the task of determining the
      effectiveness of any therapeutic step becomes difficult. With asthma, however, in
      which case it is difficult to establish the initial diagnosis, beginning a
      program of outcome measurements regarding any therapeutic interaction is nearly
      impossible. Conventional means are thwarted at the outset. One way of approaching
      the problem of obtaining reproducible outcomes data is to examine those areas in
      which measurements can be made and determine the barriers to obtaining the data.
      Establishing a good medical history is a critical step that, in general, is
      especially difficult with very young children, and tools that provide objective
      measurements that are used in the normal evaluation of older children are of
      little use in the very young child with asthma. Parts of the physical examination
      are difficult to perform in very young children, and findings associated with
      asthma can be found in other clinical states. In this age group, diary keeping
      suffers from the same problems and issues that are related to obtaining an
      accurate medical history. Barriers also exist to obtaining the best outcomes. The
      choice of medications for the very young child is limited; there are several
      typical adherence problems, and information about adverse effects is limited.

PMID- 11344379
TI  - Outcomes in pediatric asthma: What are the important issues?
AB  - Historic characteristics related to children and their parents remain the primary
      focus for diagnosis of asthma in the preschool-aged child. Important questions
      remain unanswered. Physicians must be better able to assess whether asthma is
      present. They also need to better understand the genetics of asthma and allergy
      and to have access to simple, quantitative measurements of those environmental
      exposures that enhance the risk of allergy and asthma. Physicians must also
      balance benefits and risks from any intervention, which is difficult because
      existing guidelines do not offer much information on the preschool-aged child.
      Although we are unable to prevent the development of asthma and allergy, it is
      possible to help children and their families control asthma.

PMID- 11344380
TI  - Proposed product labeling changes: does it really matter?

PMID- 11344381
TI  - High 6-thioguanine nucleotide levels and low thiopurine methyltransferase
      activity in patients with lupus erythematosus treated with azathioprine.
AB  - Azathioprine (AZA) is characterized by a high interindividual variability in
      bioavailability and metabolism. AZA is converted into 6-thioguanine nucleotides
      (6-TGN) to which the immune modifier activity is attributed. The 6-TGN levels are
      known to be affected by the activity of the key enzyme, thiopurine
      methyltransferase (TPMT), which is under genetic dependence. The authors measured
      a significantly lower TPMT activity in 53 women with systemic lupus erythematosus
      (SLE) (12.2 +/- 2.4 pmol/h/ml RBC; P < 0.01) when compared with 30 healthy
      control participants (13.15 +/- 3.1 pmol/h/ml RBC) but not with 28 patients with
      other dysimmune diseases (non-SLE; 13.0 +/- 3.0 pmol/h/ml RBC; P = 0.10). To
      evaluate the impact of TPMT activity on the concentrations of AZA metabolites, we
      measured the TPMT activity and 6-TGN levels in a subgroup of 26 patients in
      remission and treated with a stable dose of AZA (mean value: 1.9 +/- 0.5
      mg/kg/day) for at least six months (n = 13 with SLE and n = 13 with other
      dysimmune diseases, ie, non-SLE). In such a subgroup, no correlation between 6
      TGN levels and TPMT activity was observed. However, patients with SLE presented
      lower TPMT activity and higher 6-TGN levels (215 +/- 123 versus 140 +/- 75 pmol/8
      x 10(8) RBC in non-SLE patients; P < 0.04). It must be noted that transient
      increase in 6-methylmercaptopurine levels (6-MMP), a putative toxic metabolite
      (up to 21.7 nmol/8 x 10(8) RBC), was more frequently observed in the non-SLE
      group (P < 0.01). Even if a relationship was observed between low TPMT activity
      and 6-TGN levels in SLE, its clinical impact appears to be limited as far as
      regular hematologic controls are performed.

PMID- 11344382
TI  - Rifampicin pharmacokinetics with and without ciprofloxacin.
AB  - We investigated the effect of ciprofloxacin on rifampicin pharmacokinetics in
      five healthy subjects. Each subject received 600 mg rifampicin with 350 mL of
      water, and in the second phase, each subject received 600 mg rifampicin plus 500
      mg ciprofloxacin with 350 mL of water. In each of the two phases, plasma
      rifampicin levels were measured from 1 to 24 hours. Treatment with ciprofloxacin
      significantly increased the half-life and also significantly decreased the
      maximum peak concentration of rifampicin. Area under the curve time for peak
      plasma concentration and volume of distribution were not significantly affected.
      In this study, we found that ciprofloxacin increases the half-life and reduces
      the maximum concentration of rifampicin in humans.

PMID- 11344383
TI  - Prevention of contrast media-induced renal dysfunction with prostaglandin E1: a
      randomized, double-blind, placebo-controlled study.
AB  - Preexisting renal impairment is an all-encompassing risk factor for radiocontrast
      associated nephrotoxicity. Renal impairment appears to be associated with the
      inadequate production of renal prostaglandins at the critical time of
      radiocontrast administration and for a variable time period afterward. We
      prospectively studied 130 patients with chronic renal insufficiency (serum
      creatinine > or =1.5 mg/dL) who were undergoing radiocontrast administration.
      Using a double-blind, randomized, prospective technique, patients were assigned
      to either placebo or one of three prostaglandin E1 (PGE1) treatment groups (10,
      20, or 40 ng/kg/min). Infusion was started 60 +/- 30 minutes before the
      administration of radiocontrast and was continued for a total of 6 hours. In the
      placebo group, radiocontrast administration resulted in a mean increase (+/- SD)
      in serum creatinine of 0.72 +/- 1.15 mg/dL at 48 hours. This increase was less in
      each of the PGE1 treatment groups after 48 hours, with a significant difference
      between placebo and the 20 ng/kg/min PGE1 group (P = 0.01). Using baseline
      adjusted means, analysis of covariance with baseline serum creatinine as the
      covariable demonstrated significant differences between the placebo and 20
      ng/kg/min PGE1 group (P = 0.03) and between the placebo and 10 ng/kg/min PGE1
      group P = 0.047). In a subgroup analysis of the diabetic patients, the increase
      in serum creatinine was less pronounced in the three PGE1 groups versus the
      placebo group, and the 20 ng/kg/min PGE1 group had the most favorable outcome.
      The parenteral administration of PGE1 immediately before radiocontrast exposure
      and continued for a period of 5 to 5.5 hours significantly reduced the elevation
      of serum creatinine poststudy. The most effective of the three PGE1 dosing
      regimens was 20 ng/kg/min.

PMID- 11344384
TI  - Old and new drugs used in rheumatoid arthritis: a historical perspective. Part 2:
      the newer drugs and drug strategies.
AB  - After a 20-year hiatus, drug development for rheumatoid arthritis resumed in the
      early 1980s with cyclosporine, continuing in the 1990s with minocycline,
      leflunomide, and the tumor necrosis factor-alpha antagonists, infliximab and
      etanercept. Unlike the older disease-modifying antirheumatic drugs (apart from
      the cytotoxics), the newer drugs were designed with strict reference to proven
      pathophysiology in rheumatoid arthritis and, apart from minocycline, the intended
      action of these agents is highly likely the explanation for the observed
      efficacy. The evidence for the evolution of more rational drug development in
      rheumatoid arthritis has not altered the fact that efficacy versus toxicity still
      remains the major determinant in the practical use of these agents, as well as in
      the use of other, experimental agents briefly discussed. Action, efficacy, and
      toxicity also determine the rational chronologic use of these drugs alone and, in
      particular, in combination.

PMID- 11344385
TI  - Long-acting opioids for chronic pain: pharmacotherapeutic opportunities to
      enhance compliance, quality of life, and analgesia.
AB  - Effective management of chronic pain has become an increasingly critical issue in
      health care. Opioid agonists are among the most effective analgesics available
      for reducing pain perception; however, their chronic use is controversial. This
      is primarily due to regulatory barriers, misunderstandings about pain management
      among primary caregivers, fear of adverse side effects, and misconceptions about
      the potential risks of addiction. Short-acting opioids provide effective
      analgesia for acute pain but should be avoided as primary analgesics for chronic
      pain management. Long-acting opioids have greater utility than short-acting
      opioids in treating chronic pain in patients with consistent pain levels. Results
      of studies show that improved quality of life is directly related to the use of
      long-acting opioids in patients with chronic pain of both cancer and noncancer
      etiology. Short-acting opioids may be used during the initial dose titration
      period of long-acting formulations and as rescue medication for episodes of
      breakthrough pain. Clinical experience reveals that selection of an effective
      pain regimen for the patient with chronic pain, combined with aggressive
      management of side effects, leads to improved overall functioning and quality of
      life.

PMID- 11344386
TI  - Proceedings of the nineteenth annual symposium: advances in cardiovascular
      pharmacology: protocol design and methodology. the U.S. Regulatory Process. May
      3, 4, 5, 2000, Washington, D.C.

PMID- 11344387
TI  - Long-term graft acceptance in rat heart transplantation by CTLA4Ig gene
      transfection combined with FTY720 treatment.
AB  - CTLA4Ig strongly adheres to B7 molecules on antigen-presenting cells to block
      intracellular signal transduction via CD28 on helper T cells, which eventually
      inhibits immune responses. We have demonstrated that the administration to
      recipient animals of adenoviral vectors containing CTLA4Ig gene (adCTLA4Ig)
      prolonged graft survival, although the gene expression diminished in a time
      dependent manner and the grafts were finally rejected. In addition, recipient
      animals treated with FTY720, a new immunosuppressant, exhibited a decrease in the
      number of peripheral lymphocytes due to apoptosis. In this study, we performed
      adCTLA4Ig transfection combined with FTY720 treatment in heart-grafted rats to
      determine if the combination could induce a mutual effect on graft survival. The
      recipient animals were given injections of 1 x 10(9) plaque-forming units of
      adCTLA4Ig via the tail vein immediately after grafting. On the day before
      transplantation we administered FTY720 orally to some of these animals at a
      dosage of 5 mg/kg and again on the day of transplantation. The median graft
      survival period in the adCTLA4Ig-only group was 27 days, whereas that in the
      combination group was markedly prolonged to 56 days. Of 15 grafts, 5 survived
      indefinitely. In these groups we observed detectable levels of CTLA4Ig in the
      sera 49 days after grafting; the levels were always higher in the combination
      group than in the adCTLA4Ig-only group. As a result, this study revealed that
      FTY720 and adCTLA4Ig have a potent mutual effect on graft survival during rat
      heart transplantation. Furthermore, it is highly possible that FTY720 enhances
      gene expression of adCTLA4Ig, which may be related to the long-term acceptance of
      grafts.

PMID- 11344389
TI  - Distribution and functional significance of somatostatin receptors in malignant
      melanoma.
AB  - Malignant melanoma is a neuroendocrine tumor that contains somatostatin receptors
      (SSTRs). Adjuvant therapy for melanoma is limited. Because melanomas arise from
      neural crest cells, we sought to evaluate the distribution of SSTR subtypes found
      in these tumors and their functional significance by imaging with 111In
      pentetreotide scintigraphy (OctreoScan). Octreotide binds with greatest affinity
      to SSTR2 and SSTR5. Studying the expression of SSTRs in melanoma may demonstrate
      a potential role for octreotide in the treatment of melanoma. A series of 23
      melanomas from 17 patients who underwent resection of regional or distant
      metastases were evaluated for the presence of SSTRs by the reverse transcriptase
      polymerase chain reaction (RT-PCR) using primers specific for SSTR1 through
      SSTR5. Identity of RT-PCR products was confirmed by Southern blot analysis.
      Sixteen patients underwent preoperative OctreoScan. SSTR1 was expressed in 96% of
      tumors, SSTR2 in 83%, SSTR3 in 61%, SSTR4 in 57%, and SSTR5 in 9%. OctreoScan
      imaged 63% of tumors. There was no correlation between SSTR subtype expression
      and OctreoScan result. Most of the melanomas expressed mRNA for SSTR1 and SSTR2,
      with approximately half expressing SSTR3 and SSTR4. The SSTR mRNA for SSTR2
      appears to be transcribed into functional protein that binds 111In-pentetreotide
      in more than half of these patients. Although OctreoScan has limited sensitivity
      for localizing melanomas, tumors that can be imaged by OctreoScan may be amenable
      to adjuvant therapy with octreotide or targeted therapy with high-energy
      radioisotope-labeled octreotide. These studies clearly define melanoma as a
      neuroendocrine tumor, which may open new avenues for tumor control.

PMID- 11344388
TI  - Autonomic nervous system and gut-derived endotoxin: involvement in activation of
      Kupffer cells after in situ organ manipulation.
AB  - Gentle in situ organ manipulation rapidly causes disturbances in the hepatic
      microcirculation, hypoxia, and activation of Kupffer cells. Because the
      mechanisms of Kupffer cell activation after organ manipulation remain unclear,
      the possible role of the autonomic nervous system and gut-derived endotoxin were
      assessed. To mimic what occurs with major abdominal surgery, livers from female
      Sprague-Dawley rats (200-230 g) underwent minimal dissection for 12 minutes and
      were manipulated gently or were left alone for 13 subsequent minutes. Kupffer
      cells were activated 2 hours after manipulation, reflected by a significant
      increase in intracellular calcium ([Ca2+]i) from about 90 nM in unmanipulated
      controls to more than 180 nM in response to lipopolysaccharide (LPS 100 ng/ml).
      Furthermore, Kupffer cells from manipulated rats produced about threefold more
      tumor necrosis factor-alpha after LPS (100 ng/ml) than did the unmanipulated
      controls. Moreover, O2 uptake of ex situ perfused liver was increased from about
      110 micromol/g/hr in unmanipulated controls to more than 160 micromol/g/hr 2
      hours after organ manipulation. Binding of pimonidazole (120 mg/kg IV), a 2
      nitroimidazole hypoxia marker given 2 hours after manipulation, increased about
      2.5-fold, and hepatic glycogen was depleted. Two hours after organ manipulation
      gut permeability to horseradish peroxidase was elevated and endotoxin in the
      portal venous blood was increased twofold. Microsurgical hepatic denervation,
      ganglionic blockade, adrenalectomy, and antibiotics to sterilize the gut before
      manipulation prevented activation of Kupffer cells by organ manipulation.
      Hexamethonium and adrenalectomy prevented increases in gut permeability caused by
      manipulation. Although antibiotics blunted the increase in portal venous
      endotoxin significantly, there was no effect on gut permeability. These data
      indicate for the first time that both the autonomic nervous system and gut
      derived endotoxin are involved in activation of Kupffer cells after organ
      manipulation.

PMID- 11344390
TI  - Factors predicting nutritional derangements in patients with obstructive
      jaundice: multivariate analysis.
AB  - Patients with obstructive jaundice (OJ) that requires surgery often have
      malnutrition associated with increased perioperative morbidity. This study
      investigated the factors influencing nutritional derangements in these patients.
      A series of 46 OJ patients were investigated prospectively (28 malignant tumors,
      18 benign obstructions). A nutritional risk index of < 83.5 was used to define
      protein-calorie malnutrition. Liver function, cholecystokinin (CCK), tumor
      necrosis factor-alpha (TNFalpha), and endotoxin levels were determined. A
      multivariate analysis was performed, and an obstructive jaundice malnutrition
      index (OJMI) was obtained. Altogether, 22 (48%) OJ patients had malnutrition (33%
      with benign obstructions, 57% with malignant disease). Malnourished patients had
      higher serum bilirubin levels (258 +/- 120 vs. 154 +/- 62 mmol/L; p = 0.005),
      longer duration of jaundice (16 +/- 9 vs. 9 +/- 5 days; p = 0.03), and higher
      plasma levels of CCK (4.0 +/- 1.3 vs. 1.7 +/- 1.0 pmol/L; p = 0.005), alanine
      aminotransferase (ALT) (226 +/- 209 vs. 187 +/- 161 UI/L; p = 0.01), endotoxin
      (15 +/- 10 vs. 6.5 +/- 7.0 EU/L; p = 0.007), and TNFalpha (69 +/- 82 vs. 23 +/-
      15 pg/ml; p = 0.008) than those without malnutrition. However, only serum
      bilirubin, CCK, ALT, and patient age were predictors for malnutrition by
      multivariate analysis. Malnutrition might be expected (95% confidence interval)
      in patients older than 68 years with increased bilirubin (> 290 mmol/L) and ALT
      (> 210 UI/L) levels that corresponded with an OJMI > 55. It was concluded that
      nutritional alterations in patients with obstructive jaundice were determined by
      the intensity of the biliary obstruction correlated with increased plasma CCK
      levels as well as with liver dysfunction and patient age.

PMID- 11344391
TI  - Identification and management of intravagal parathyroid adenoma.
AB  - Intravagal parathyroid adenomas are rare, with only three cases reported in the
      English literature. The objective of this report is to describe two additional
      patients with hyperfunctioning parathyroid glands found within the vagus nerve
      and to define the anatomy of this finding. Both patients presented with a history
      of persistent hyperparathyroidism despite multiple therapeutic interventions. A
      high cervical localization was established in both cases by selective venous
      sampling. In each patient successful removal of the intravagal parathyroid gland
      was achieved with subsequent resolution of calcium and parathyroid levels. Each
      adenoma was located within the vagus nerve below the level of the carotid
      bifurcation and was enucleated without sacrificing the vagus nerve. In our cases
      and those reported previously, the parathyroid glands were supernumerary,
      representing parathyroid tissue embryologically derived from the third branchial
      pouch. Exploration for hyperparathyroidism requires a complete, meticulous
      surgical dissection to identify all parathyroid glands and to search for possible
      accessory tissue in selected cases. Our experience and a review of the literature
      serve to emphasize that, although rare, intravagal parathyroid adenomas do occur.
      Examination of the vagus nerve should therefore be strongly considered when four
      normal glands are found, as intravagal adenomas appear to represent accessory
      ectopically located parathyroid tissue.

PMID- 11344392
TI  - Optimum treatment strategy for superficial esophageal cancer: endoscopic mucosal
      resection versus radical esophagectomy.
AB  - This study was designed to determine the optimum treatment for a superficial
      esophageal cancer involving the mucosal or submucosal layer of the esophagus. The
      subjects were 150 patients with a superficial esophageal cancer who underwent
      endoscopic mucosal resection (EMR) or esophagectomy in Kurume University Hospital
      from 1981 to 1997. The mortality and morbidity rates, survival rate, and
      recurrence rate were retrospectively compared for (1) 35 patients who underwent
      EMR and 37 patients who underwent esophagectomy for a mucosal esophageal cancer
      and (2) 45 patients who underwent extended radical esophagectomy and 33 patients
      who underwent less radical esophagectomy for a submucosal esophageal cancer.
      Among the 72 patients with a mucosal cancer, lymph node metastasis/recurrence was
      observed in only one (1%); whereas of 78 patients with a submucosal cancer it was
      observed in 30 (38%). Among patients with a mucosal cancer the mortality and
      morbidity rates after EMR were lower than for those after esophagectomy. The
      survival rate after EMR was the same as that after esophagectomy. No recurrence
      was observed after either treatment modality. Among the patients with a
      submucosal cancer, the survival rate was higher and the recurrence rate lower
      after extended radical esophagectomy; than after less radical esophagectomy; the
      mortality and morbidity rates after extended radical esophagectomy were the same
      as those after less radical esophagectomy. Multivariate analysis demonstrated
      that the treatment modality (EMR versus esophagectomy) did not influence the
      survival of patients with a mucosal esophageal cancer, whereas it strongly
      influenced the survival of patients with a submucosal esophageal cancer. We
      concluded that EMR was the mainstay of treatment for a mucosal esophageal cancer,
      and extended radical esophagectomy was the mainstay of treatment for a submucosal
      esophageal cancer.

PMID- 11344393
TI  - Temporary pancreatic duct occlusion by ethibloc: cause of microcirculatory
      shutdown, acute inflammation, and pancreas necrosis.
AB  - Temporary obliteration of the pancreatic duct has been suggested to be beneficial
      in chronic pancreatitis, segmental pancreatic transplantation, and following Roux
      Y pancreaticojejunostomy. Little is known, however, as to whether obliteration of
      the duct alters exocrine pancreatic physiology. Therefore we studied in male
      inbred Lewis rats the immediate effects of Ethibloc-induced duct obliteration
      (Ethibloc: Ethicon, Norderstedt, Germany) on pancreatic microcirculation,
      inflammation, and tissue injury (n = 8), and compared these effects with those
      caused by experimental pancreatitis (4% sodium taurocholate; n = 8). Animals
      receiving an intraductal infusion of saline served as controls (n = 8). Duct
      occlusion with Ethibloc resulted in a marked decrease (p < 0.05) in capillary red
      blood cell (RBC) velocity and functional capillary density (FCD) to 88 +/- 39
      microm/s (baseline 716 +/- 40 microm/s) and 72 +/- 33 cm(-1) (baseline 493 +/- 21
      cm(-1)), respectively, which was even more pronounced when compared with that
      observed in experimental pancreatitis (333 +/- 62 microm/s and 195 +/- 44 cm(-1),
      respectively). In parallel, the manifestation of tissue damage was found to be
      more severe after Ethibloc; and chloracetate esterase staining showed a larger
      number of infiltrating leukocytes [555 +/- 86/high power field (HPF) versus
      pancreatitis: 160 +/- 12/HPF; p < 0.05). We conclude that intraductal application
      of Ethibloc induces significant microcirculatory failure and a marked
      inflammatory response, which are even more pronounced when compared with the
      changes observed with experimental pancreatitis. Based on these results and the
      fact that there is no direct proof for a benefit of temporary duct occlusion by
      Ethibloc, it is proposed that the procedure be reevaluated for its use in
      pancreatic surgery.

PMID- 11344394
TI  - Outcome of surgical intervention for rectoneovaginal fistulas in Mayer-Rokitansky
      Kuester-Hauser syndrome.
AB  - Creation of a neovagina to treat vaginal atresia or aplasia in Mayer-Rokitansky
      Kuester-Hauser syndrome must always be followed by long-term application of
      dilators to avoid shrinkage. However, rectoneovaginal fistulas are caused by
      chronic alteration and consecutive necrosis of the posterior neovaginal wall. We
      evaluated retrospectively the postoperative outcome of rectal wall and neovaginal
      reconstruction using a standardized surgical technique in an exclusive collection
      of women. Eight women with a mean age of 28 years (range 22-31 years) were
      treated for rectoneovaginal fistulas in our clinic. Preoperatively, proctoscopy,
      sphincter manometry, endoluminal rectal ultrasonography, and colonoscopy were
      performed; and regular postoperative follow-up by digital examination and
      rectoscopy were obligate. The standard surgical procedure via a perineal approach
      included fistulectomy and closure of the mucosa and rectal wall followed by a
      levatorplasty. All but one woman had a temporary colostomy. After 2 weeks the
      patients were allowed to wear vaginal dilators of a smaller size. Within the mean
      follow-up period of 20 months, reintervention was necessary twice because of late
      fistula relapse detected by proctoscopy, barium enema, and subjective symptoms.
      Morbidity was 25% (n = 2) due to secondary superficial wound healing or urinary
      tract infection. The average time of the hospital stay was 13 days (10-14 days).
      One patient complained of vaginal shrinkage and underwent local estrogen therapy
      with a good functional result 3 months later. Proper fistulectomy and surgical
      reconstruction with interpositioning of well perfused muscle layers achieved good
      functional outcome with an acceptable number of minor morbidities. Local estrogen
      treatment is helpful for avoiding scarification and decreasing the neovaginal
      size.

PMID- 11344395
TI  - Prospective randomized comparison of two preoperative skin preparation techniques
      in a developing world country.
AB  - Povidone-iodine (PI) is a scarce and expensive item for some hospitals in
      developing countries. This prospective, randomized study was performed at Baptist
      Medical Centre (BMCO) in Ogbomoso, Nigeria to determine if the use of PI for
      preoperative skin preparation would result in a lower postoperative wound
      infection rate and to identify other factors influencing the infection rate. Two
      hundred patients undergoing inguinal hernia repair were randomized to receive
      skin preparation with either: (1) locally available, inexpensive market soap and
      methylated spirit or (2) imported PI. The two groups were equally stratified. The
      overall postoperative wound infection rate was 5.5%, and there was no significant
      difference between the groups (5.1% vs. 5.9%). Factors that did not affect the
      infection rate included gender, age, type of anesthesia, type or duration of the
      operative procedure, and number of breaks in optimal technique. There were eight
      abscesses and three cases of cellulitis without suppuration diagnosed an average
      of 10 days postoperatively. Staphylococcus was the only bacterium identified on
      Gram stain or culture. The expense of procuring PI is not justified at BMCO.
      Available funds may better be used for preoperative antibiotics or for
      improvement in hospital infrastructure, which should result in fewer breaks in
      optimal operating room technique.

PMID- 11344396
TI  - Van Swieten and the renaissance of the Vienna Medical School.
AB  - The period until 1745 found the Viennese medical system languishing far behind
      advances made in other major European centers. This chaotic situation was
      reversed by the foresight and breadth of vision of the Empress Maria Theresa, who
      initiated considerable reform in Austria by actively recruiting the best minds of
      the time to reduce the intellectual and technologic differences. Her ability to
      entice one of Boerhaave's most eminent pupils, Gerard van Swieten, to leave
      Leiden for Vienna, particularly benefited the Vienna Medical School. In 1745 van
      Swieten assumed responsibility for reconfiguration of the patronage and nepotism
      ridden medical system of the Austro-Hungarian Empire. As a first task, he swiftly
      expunged the influence of the Jesuits and other religious orders from medicine
      and established formal training and examinations, transforming the medical
      discipline into a meritocracy. Excelling as a physician and an innovative
      teacher, he also established a close personal relationship with the Empress and
      became her medical confidante. To a large part, the success of this first great
      Viennese medical school was owed to de Haen, who left Leiden to implement
      Boerhaave's method of clinical teaching. As a result of these innovations and
      with considerable support from the Empress, the University of Vienna,
      particularly its medical school, within a few decades achieved recognition
      throughout Europe as a seat of learning and scholarship. Van Swieten would not be
      remembered today if his contribution had been only scholarly or scientific
      achievements. He propelled Austrian medicine to a level commensurate with that of
      other European states of the day by 27 years of dedicated and industrious
      service.

PMID- 11344397
TI  - Pancreatic surgery and glucose regulation: introduction.

PMID- 11344398
TI  - Pancreatic resection: effects on glucose metabolism.
AB  - Pancreatic resection results in hormonal abnormalities that are dependent on the
      extent and location (proximal versus distal) of the resected portion of the
      gland. The form of glucose intolerance which results from pancreatic resection is
      termed pancreatogenic diabetes. It is associated with features distinct from both
      type I (insulin-dependent) and type II (insulin-independent, or adult-onset)
      diabetes. Hepatic insulin resistance with persistent endogenous glucose
      production and enhanced peripheral insulin sensitivity result in a brittle form
      of diabetes which can be difficult to manage. In addition to insulin deficiency,
      the endocrine abnormalities that accompany pancreatic resection can include
      glucagon deficiency or pancreatic polypeptide (PP) deficiency if the resection is
      distal or proximal, respectively. Glucagon deficiency can contribute to
      iatrogenic hypoglycemia, and PP deficiency can contribute to persistent
      hyperglycemia due to impaired hepatic insulin action. Pancreatic resections that
      spare the duodenum, such as distal pancreatectomy, duodenum-preserving pancreatic
      head resection (Beger procedure), or extended lateral pancreaticojejunostomy with
      excavation of the pancreatic head (Frey procedure), are associated with a lower
      incidence of new or worsened diabetes than the standard or pylorus-preserving
      pancreaticoduodenectomy (Whipple procedure) or total pancreatectomy. Operative
      considerations for the treatment of pancreatic disease should include strategies
      to minimize the hormonal impairment of pancreatic resection.

PMID- 11344399
TI  - Overview of glucose regulation.
AB  - Glucose homeokinesis is a remarkable process that provides glucose to the body
      for energy and a constant source of glucose to the brain while preventing
      hyperglycemia. The latter leads to excessive glycosylation of proteins, changing
      their structure and function and eventually affecting every organ system in the
      body. Despite a variable diet of feast and famine throughout the day, the body
      maintains strict blood glucose levels through a remarkable network between the
      pancreas, liver, adipose tissue, muscle, and brain. These interactions and both
      glucose production and utilization are discussed. Glucose production is governed
      by the liver, which can generate free glucose from hepatic glycogen stores and de
      novo through gluconeogenesis. Specific glucose transporters found on every cell
      of the body administer glucose utilization. Each transporter works with a
      different serum glucose level. The mechanism of these transporters and the
      specific glucose cycles are discussed. The purpose of this article is to review
      glucose regulation; it serves as a reference for the other presentations of this
      symposium.

PMID- 11344401
TI  - Impact of bone marrow transplantation on type I diabetes.
AB  - Type I diabetes is a systemic autoimmune disease. Evidence is accumulating that
      autoimmune diseases such as type I diabetes are linked to the bone marrow
      hematopoietic stem cell (HSC) itself rather than its derivatives. HSC chimerism
      achieved through bone marrow transplantation (BMT) may affect type I diabetes in
      two ways: first, to induce tolerance to pancreas and islet cell transplants; and
      second, to reverse the autoimmune process prior to the development of terminal
      complications. Transplantation of bone marrow from normal donors into patients
      with hematologic malignancy and coexistent type I diabetes has reversed the
      systemic diabetic autoimmune process. Donor HSCs can also be utilized for the
      induction of donor-specific tolerance to islet cell transplants. Islet or whole
      pancreas transplantation is the most physiologic approach to treating type I
      diabetes. Currently, this is limited by the requirement for high-dose chronic
      nonspecific immunosuppression to prevent rejection. Despite these agents, chronic
      rejection remains the primary cause for late graft loss. Donor-specific tolerance
      eliminates the requirement for immunosuppression and prevents the development of
      chronic rejection. Bone marrow transplantation does have limitations. In
      particular these limitations include the morbidity associated with lethal
      conditioning, graft-versus-host disease, and failure of engraftment. Currently
      the morbidity and mortality associated with lethal conditioning could not be
      justified for tolerance induction or interruption of the autoimmune state in type
      I diabetes. The goal of current research is to identify those factors in both
      recipient and donor that optimize engraftment to reverse the risk/benefit ratio
      associated with BMT. This article reviews the state of the art for HSC chimerism
      affecting diabetes.

PMID- 11344400
TI  - Endocrine pancreas: summary of observations generated by surgical fellows.
AB  - The present article summarizes scientific observations of the endocrine pancreas
      anatomy and physiology into a unifying hypothesis. The data were generated over
      the years by surgical fellows using human and rat isolated perfused pancreas
      models and in vivo islet microcirculation models. The endocrine pancreas secretes
      a hormonal milieu regulated by neural, hormonal, and nutritional stimuli and the
      microcirculation. Variation of the nutrient and hormone concentrations in the
      islet capillaries generates two levels of response. A first level of response is
      in the central nervous system (CNS). Cholinergic signals from the CNS regulate
      the islet microcirculation through internal and external gates. This regulation
      is mediated by nitric oxide (NO). The gates are endothelial cells found in
      feeding arterioles and capillaries of the islet capable of directing blood flow
      through changes in cellular shape. External gates shunt flow to the entire
      endocrine pancreas, and internal gates divert blood flow within the islet to
      expose selectively the appropriate cell type required for changes in hormonal
      milieu. The second level is within the islet. The islet cells respond directly to
      variations in hormonal and nutrient concentrations. There is extensive
      communication between the various types of islet cells regulated by NO and
      hormonal feedback loops. The two levels of response allow an appropriate hormonal
      milieu, which secreted into the bloodstream contributes to the maintenance of
      glucose homeostasis.

PMID- 11344402
TI  - Human islet transplantation: update.
AB  - New hope for the treatment of type 1 diabetes has recently emerged from the
      encouraging results of islet cell transplantation in humans during the last few
      years. Although still facing considerable problems, the challenge to achieving
      insulin independence has been overcome in some patients who received an islet
      graft. However, the success of clinical trials is still limited by the inability
      to transplant enough viable human islets to compensate for the insulin-deficient
      state, the number of islets that engraft following transplantation, the rejection
      process, and the recurrence of autoimmunity. The important advances in
      immunosuppressive regimens, organ procurement techniques, isolation techniques,
      and availability of defined collagenase blends have contributed to the continuing
      promise of making islet cell transplantation the treatment of choice for type 1
      diabetes mellitus.

PMID- 11344403
TI  - Pancreas transplantation for treatment of diabetes mellitus.
AB  - Pancreas transplantation is the only treatment for type I diabetes mellitus that
      can induce an insulin-independent normoglycemic state. Because of the need for
      immunosuppression, it has been most widely applied in uremic diabetic recipients
      of kidney transplant with a high success rate, particularly when done as a
      simultaneous (SPK) procedure (insulin independence > 80% at 1 year) with patient
      and kidney graft survival rates equivalent to or higher than in those who receive
      a kidney transplant alone. The results of solitary pancreas transplants (PAK in
      nephropathic diabetic recipients or PTA in nonuremic recipients) have also
      dramatically improved; 1-year graft survival rates are more than 80% and 70%,
      respectively, with the new immunosuppressants tacrolimus and mycophenolate
      mofetil. Multiple factors are important for successful application of pancreas
      transplantation, as summarized in this review.

PMID- 11344404
TI  - Islet transplantation and glucose regulation.
AB  - Transplantation of isolated islets of Langerhans for treatment of diabetes has
      been developed through experimental research in several species and is now being
      applied to humans with some success albeit limited. A significant problem for
      human islet allotransplantation or autotransplantation (following pancreatectomy)
      is the relatively poor yield of islets available for transplantation. The
      metabolic function of islet transplant recipients that have achieved insulin
      independence reflects the relatively small mass of insulin-secreting tissue
      implanted and the fact that only the intraportal site of transplantation appears
      to allow sufficient graft function to achieve insulin independence. The long-term
      function of such grafts has been poor, with most grafts showing deterioration in
      function within 5 years. Studies of islet transplantation in other species showed
      a similar result, although other sites for islet graft implantation, such as the
      spleen or kidney capsule, may be associated with a better outcome. These studies,
      however, also suffer from problems of relatively limited islet mass. Only in the
      rodent model where isogeneic strains are available is it possible to transplant
      sufficient numbers of islets to obtain an equivalent functional islet mass
      similar to that found in the normal pancreas; and in this case near-normal
      glucose metabolism is obtained and is maintained for the life-span of the animal.

PMID- 11344405
TI  - Revascularization and microcirculation of freely grafted islets of Langerhans.
AB  - A considerable number of experimental studies have demonstrated that the
      reestablishment of an appropriate microvascular supply is an essential
      prerequisite for successful pancreatic islet transplantation. Freely transplanted
      islets show the first signs of angiogenesis (i.e., capillary sprout formation and
      protrusion) as early as 2 days after transplantation, and the entire
      vascularization process is completed after 10 to 14 days. Cryopreservation and
      culture of the isolated islets before transplantation and hyperglycemia of the
      transplant recipient seem not to affect the vascularization process essentially.
      In addition, immunosuppressive drugs, such as cyclosporin A and 15
      deoxyspergualin, do not or only slightly inhibit revascularization of syngeneic
      islets; however, they are not able to prevent completely xenograft-induced
      microvascular perfusion failure. In contrast, novel immunosuppressants (e.g., RS
      61443) or dietary supplementation of the antioxidant vitamin E were shown to
      prevent microvascular graft rejection almost completely, including leukocyte
      recruitment and capillary perfusion failure. Thus the development of novel
      strategies to improve posttransplant islet function should include concepts that
      accelerate the vascularization process and protect the newly formed
      microvasculature from rejection-mediated injury. The improvement of islet graft
      vascularization and the maintenance of adequate microvascular perfusion will
      contribute to the increased success of pancreatic islet transplantation.

PMID- 11344406
TI  - Whole organ transplantation and glucose regulation.
AB  - Pancreas transplantation has gained clinical acceptance since its initial
      application more than 30 years ago. A constellation of surgical, pharmacologic,
      and metabolic alterations occur with transplantation, particularly if pancreatic
      transplantation is performed in addition to renal transplantation in a uremic
      diabetic. Increasingly sophisticated studies have allowed analysis of the
      performance of the transplanted organ and have enhanced our basic understanding
      of insulin's complex interplay in peripheral glucoregulatory processes.

PMID- 11344407
TI  - Insulin pumps and glucose regulation.
AB  - With recent technologic advances there has been a resurgence of interest in
      implantable insulin infusion devices. A satisfactory closed loop system has been
      elusive. Open loop systems include the pump, delivery catheter, and patient pump
      communicator. Several such systems are currently undergoing clinical
      investigation. Implantable pumps can be placed with minimal morbidity. Insulin
      underdelivery is the most frequent long-term problem. Several recent studies
      suggest that implantable pumps can safely and effectively maintain good glucose
      control. The development of a satisfactory implantable closed loop system will be
      the next step in this technology.

PMID- 11344408
TI  - Etiology of type II diabetes mellitus: role of the foregut.
AB  - The Greenville version of the gastric bypass induced long-term remission of type
      II diabetes mellitus in 121 of 146 (82.9%) morbidly obese patients. Similarly,
      the operation returned 150 of 152 (98.7%) morbidly obese patients with impaired
      glucose tolerance to euglycemia. These outcomes were not merely changes in
      glucose levels; the operation also reduced the mortality and morbidity of the
      disease. Diabetic patients submitted to surgery had a 1.0% chance of dying during
      a 10-year period of follow-up compared to a mortality rate of 4.5% in a matched
      group (p = 0.0003). These results, the best therapeutic outcomes for type II
      diabetes ever reported, suggest that the disease is not an untreatable, hopeless
      illness but one that can be treated successfully with better understanding of the
      pathophysiology of these surgical remissions. The mechanism of the improvement is
      not yet clear. The rapidity of the correction to euglycemia, usually a matter of
      days, suggests that the reason is not the loss of weight (i.e., reduction in fat
      mass) but, rather, the result of the exclusion of food and a secondary alteration
      in incretin signals from the antrum, duodenum, and proximal jejunum to the
      islets.

PMID- 11344409
TI  - Re: gastrointestinal anastomosis.

PMID- 11344410
TI  - Re: The leech and the physician.

PMID- 11344412
TI  - Re: Surgery for ductal adenocarcinoma of the pancreatic head.

PMID- 11344413
TI  - Re: Reconstructive intestinal surgery after open management of severe
      intraabdominal infection.

PMID- 11344420
TI  - Laparoscopic surgery in Europe-Development and education.

PMID- 11344421
TI  - Accomplishments and challenges of surgical simulation.
AB  - For nearly a decade, advanced computer technologies have created extraordinary
      educational tools using three-dimensional (3D) visualization and virtual reality.
      Pioneering efforts in surgical simulation with these tools have resulted in a
      first generation of simulators for surgical technical skills. Accomplishments
      include simulations with 3D models of anatomy for practice of surgical tasks,
      initial assessment of student performance in technical skills, and awareness by
      professional societies of potential in surgical education and certification.
      However, enormous challenges remain, which include improvement of technical
      fidelity, standardization of accurate metrics for performance evaluation,
      integration of simulators into a robust educational curriculum, stringent
      evaluation of simulators for effectiveness and value added to surgical training,
      determination of simulation application to certification of surgical technical
      skills, and a business model to implement and disseminate simulation successfully
      throughout the medical education community. This review looks at the historical
      progress of surgical simulators, their accomplishments, and the challenges that
      remain.

PMID- 11344422
TI  - Virtual reality computer simulation.
AB  - BACKGROUND: Objective assessment of psychomotor skills should be an essential
      component of a modern surgical training program. There are computer systems that
      can be used for this purpose, but their wide application is not yet generally
      accepted. The aim of this study was to validate the role of virtual reality
      computer simulation as a method for evaluating surgical laparoscopic skills.
      METHODS: The study included 14 surgical residents. On day 1, they performed two
      runs of all six tasks on the Minimally Invasive Surgical Trainer, Virtual Reality
      (MIST VR). On day 2, they performed a laparoscopic cholecystectomy on living
      pigs; afterward, they were tested again on the MIST VR. A group of experienced
      surgeons evaluated the trainees' performance on the animal operation, giving
      scores for total performance error and economy of motion. During the tasks on the
      MIST VR, errors and noneconomy of movements for the left and right hand were also
      recorded. RESULTS: There were significant correlations between error scores in
      vivo and three of the six in vitro tasks (p < 0.05). In vivo economy scores
      correlated significantly with non-economy right-hand scores for five of the six
      tasks and with non-economy left-hand scores for one of the six tasks (p < 0.05).
      CONCLUSION: In this study, laparoscopic performance in the animal model
      correlated significantly with performance on the computer simulator. Thus, the
      computer model seems to be a promising objective method for the assessment of
      laparoscopic psychomotor skills.

PMID- 11344423
TI  - A pilot study of new approaches to teaching anatomy and pathology.
AB  - PURPOSE: Minimally Invasive Surgery (MIS) has impacted patient care as well as
      medical training. New medical education opportunities have emerged with MIS. In
      this pilot study we explore the role of live, interactive MIS to augment and
      strengthen specific segments of the undergraduate medical curriculum. METHODS:
      Laparoscopic cholecystectomy (LC) was selected to demonstrate upper abdominal
      anatomy and pathology. Second year medical students (n=100) in the course of
      their GI pathology classes attended live LC telesurgery-the telesurgery student
      group (TSG). Because of technical difficulties, a second class of medical
      students (n=90) was shown the tape of the MIS procedure one year later instead of
      the live surgery-the videotape surgery group (VSG). Background clinical
      information was provided by the program director and the durgeon. During the live
      and taped LC broadcast living anatomy was demonstrated and a diseased gallbladder
      was resected. TSG students were able to ask questions of the program director and
      the surgeon and vice versa using telesurgery technology. After the procedure, the
      surgeon met with the students for further discussion. VSG students were able to
      ask questions of the program director during and after the program. Both groups
      of students completed a pre- and posttest using remote audience responders.
      Students' responses from the two groups were compared for selected test and
      evaluation items. RESULTS: Pre-test (Cronbach's alpha=.10) and post-test
      (Cronbach's alpha =.28) data were obtained from 73 students in the TSG and.22
      and.54 respectively from 69 students in the VSG. A significant increase in
      laparoscopic anatomy knowledge was observed from pretest to posttest for the VSG
      (31-55%) and from the TSG (30-61%). The majority of VSG students (68%) indicated
      the method used to teach was outstanding, and 87% indicated that the program was
      outstanding in keeping their interest. This is contrasted with only 24% of the
      TSG group responding that the teaching method was outstanding, and 41% indicated
      that the program was outstanding in keeping their interest. CONCLUSIONS: Medical
      students can productively be exposed to surgical methods and living anatomy using
      telesurgery. The high regard the TSG students had for this program suggests that
      it can be used effectively to teach and inspire medical students. The positive
      results have encouraged us to have a backup instructional method such as a tape
      of the MIS procedure, it apparently does not have the positive impact of live
      surgery.

PMID- 11344424
TI  - A prospective analysis of 13,580 colonoscopies. Reevaluation of credentialing
      guidelines.
AB  - BACKGROUND: The aims of this study were to assess the safety and efficacy of
      surgeons performing colonoscopy, and to use the results to reevaluate currently
      available credentialing guidelines. METHODS: A prospective outcomes study was
      designed to include all members of the Society of American Gastrointestinal
      Endoscopic Surgeons (SAGES). End points were related to the efficacy and safety
      of colonoscopy. Credentialing guidelines were reviewed. RESULTS: Between April
      1998 and September 1999 13,580 colonoscopies were prospectively entered into a
      database. The most common indications were rectal bleeding, colonic polyps, and
      change in bowel habits. The colonoscopy was normal or revealed only
      diverticulosis or nonspecific inflammation in 8,473 (62.4%), lower
      gastrointestinal bleeding in 4 (0.03%), polyps in 4,645 (34.2%), and tumors in
      458 (3.4%) patients. The most common biopsy methods for polyps or tumors were the
      snare (n = 1,728; 34%), the hot (n = 1,600; 31%), and the cold (n = 1,340; 22%)
      procedures. The colonoscopy was complete in 12,495 cases (92%), requiring a mean
      procedure time of 22.7 min (range, 1-170 min). Intraprocedural complications
      included arrhythmia (n = 14; 0.1%), bradycardia (n = 115; 0.8%), hypotension (n =
      171; 1.2%), and hypoxia (n = 806; 5.6%). Postprocedural complications were seen
      in 27 patients (0.2%). Bleeding (n = 10; 0.07%) was managed by observation alone
      (n = 9; 0.06%) and repeat colonoscopy with transfusion (n = 1; 0.01%).
      Perforation (n = 10; 0.07%) was treated successfully by observation with
      conservative management (n = 5; 0.05%) and surgery (n = 5; 0.05%); severe
      abdominal pain (n = 4; 0.03%) was managed by observation and conservative
      therapy; and bronchospasm (n = 2; 0.015%) was managed by observation and
      supportive care. One single mortality (0.007%) was that of a 70-year-old man with
      a massive lower gastrointestinal hemorrhage who had a cardiac arrest in the
      recovery room following colonoscopy. The complication rate was not significantly
      associated statistically with either the level of experience or the number of
      prior or annual colonoscopies. However, prior colonoscopic experience did have an
      impact on the completion rate (p < 0.001) and was inversely proportional to the
      time to completion (p < 0.001). Similarly, the number of annual colonoscopies
      affected the completion rate and was inversely correlated with the time to
      completion (p < 0.001). CONCLUSIONS: This large prospective outcomes study showed
      that colonoscopy performed by surgeons can be rapidly and successfully done with
      acceptably low morbidity and mortality. There was no association between
      experience and complications. However, a minimum of 50 prior colonoscopies and
      100 annual colonoscopies were associated with a significant improvement in the
      rate of completion. There was also a significant correlation between both prior
      and ongoing annual experience and the time required for the examination. No
      minimum number of cases can be mandated for credentialing to perform "safe"
      colonoscopies.

PMID- 11344425
TI  - Colonoscopy in octogenarians and older patients.
AB  - INTRODUCTION: Colonoscopy in the elderly has been considered by many to be risky
      because of mechanical bowel preparation and dehydration, electrolyte
      disturbances, conscious sedation, and hypoxic complications. We hypothesized that
      colonoscopy in octogenarians and older patients is a safe procedure. MATERIALS
      AND METHODS: A retrospective review of 803 patients who underwent colonoscopy
      from January 1997 to October 1997 was performed. The patients were grouped by
      age: group A (17-49 years) had 166 patients (20%); group B (50-79 years) had 534
      patients (67%); and group C (80 years and older) had 103 patients (13%). Results
      were considered significant at p value less than 0.05 unless otherwise noted.
      RESULTS: Blood in the stool (84%) and history of colonic vascular disease (5.8%)
      were the most common indication in group C (84%). Colonoscopy was used in group A
      (18%) more often than in the other groups to rule out inflammatory bowel disease.
      History of colon polyps was a more common indication in group B (20%) than in the
      other groups. Group A had a significantly higher incidence of normal examinations
      (84%) and diagnosis of inflammatory bowel disease (14%). Group B had a higher
      incidence of polyps than the other groups. Group C had the highest incidence of
      vascular disease (15%). Diverticular disease and carcinoma were more common in
      groups B (37%) and C (52%). The amount of sedation in the groups did not
      significantly differ. Completion of the colonoscopy to the cecum or anastomotic
      sites did not differ among the groups (p > 0.05), nor did complication rates
      among groups (p > 0.05). CONCLUSIONS: Colonoscopy is safe in octogenarians and
      older patients. Age does not, by itself, confer an increased risk to the
      procedure.

PMID- 11344427
TI  - Nissen fundoplication improves gastric motility in patients with delayed gastric
      emptying.
AB  - BACKGROUND: Fundoplication hastens gastric emptying in pediatric patients with
      gastroesophageal reflux disease (GERD). However, among adult GERD patients with
      impaired gastric emptying, the degree of improvement offered by fundoplication
      and the value of pyloroplasty are less well defined. Therefore, we compared
      outcomes in GERD patients with delayed gastric emptying after fundoplication
      alone or fundoplication with pyloroplasty. METHODS: Of 616 consecutive GERD
      patients who submitted to primary fundoplication (601 laparoscopic) between
      October 1991 and October 1997, 82 underwent preoperative solid-phase nuclear
      gastric emptying analysis. Of these, 25 had delayed gastric emptying (half-time
      >100 min). Of 12 patients with emptying half-times between 100 and 150 min, one
      underwent pyloroplasty at the time of Nissen fundoplication. Of 13 patients with
      emptying half-times >150 min, 11 had pyloroplasty at the time of Nissen
      fundoplication. Patients were asked to use a 0 ("none") to 4 ("incapacitating")
      scale to describe the severity of their symptoms of heartburn, regurgitation,
      dysphagia, bloating and diarrhea preoperatively and at 6 weeks and 1 year
      postoperatively. Eight patients consented to a postoperative analysis of gastric
      emptying. RESULTS: One year after fundoplication, patients with delayed gastric
      emptying and controls reported a similar improvement in heartburn, regurgitation,
      and dysphagia, with no increase in undesirable side effects such as bloating and
      diarrhea. Among the patients with delayed gastric emptying who consented to
      undergo a repeat gastric emptying study after their operation, fundoplication
      alone provided a 38% improvement (p < 0.05) in gastric emptying, whereas
      fundoplication with pyloroplasty resulted in a 70% improvement in gastric
      emptying (p < 0.05). CONCLUSION: Fundoplication improves gastric emptying. The
      addition of pyloroplasty results in even greater improvement and may have
      particular value for patients with severe gastric hypomotility.

PMID- 11344426
TI  - Is a dissection balloon beneficial in totally extraperitoneal endoscopic
      hernioplasty (TEP)? A randomized prospective multicenter study.
AB  - BACKGROUND: Laparoscopic hernioplasty has been criticized because of its
      technical complexity and increased costs. Disposable dissection balloons can be
      used to facilitate the creation of the initial working space in totally
      extraperitoneal endoscopic hernioplasty (TEP), but their use adds to the cost of
      the operation. METHODS: A total of 322 men with unilateral, primary, or recurrent
      inguinal hernias were randomized to undergo TEP with or without a dissection
      balloon. RESULTS: In the group with the balloon, three of 161 patients (2.5%)
      required conversion to transabdominal preperitoneal hernioplasty (TAPP), or open
      herniorraphy, whereas 17 of 161 patients (10.6%) were converted to TAPP or open
      herniorraphy in the group without the balloon (p = 0.002). The mean operation
      time was 55 min in the group with the balloon and 63 min in the group without the
      balloon (p = 0.004). There was no difference between them in postoperative
      morbidity, and there were no major complications in either group. The recurrence
      rate was 3.1% in the group with the balloon and 3.7 % in the group without the
      balloon (p = 0.8). CONCLUSION: The use of a dissection balloon in TEP reduces the
      conversion rate and may be especially beneficial early in the learning curve.

PMID- 11344428
TI  - Trocar and Veress needle injuries during laparoscopy.
AB  - BACKGROUND: Inadvertent lesions of the intraabdominal organs and vessels caused
      by trocars and Veress needles are rare but serious complications of laparoscopic
      surgery. Establishing the pneumoperitoneum is believed to be the most dangerous
      step. METHODS: The Swiss Association for Laparoscopic and Thoracoscopic Surgery
      (SALTS) prospectively collected the data on 14,243 patients undergoing various
      standard laparoscopic procedures between 1995 and 1997. This database was
      investigated with special regard to intraabdominal complications caused by
      trocars and Veress needles. RESULTS: There were 22 trocar and four needle
      injuries (incidence, 0.18%). Nineteen lesions involved visceral organs; the
      remaining seven were vessel injuries. The small bowel was the single most
      affected organ (six cases), followed by the large bowel and the liver (three
      cases each). All vascular lesions, except for one laceration of the right iliac
      artery, occurred as venous bleeding of either the greater omentum or the
      mesentery. Fourteen trocars were inserted under direct vision. Nineteen trocar
      injuries were recognized intraoperatively; diagnoses of two small bowel and one
      bladder injuries were made postoperatively. Needle injuries were all diagnosed
      intraoperatively. Only five injuries could be repaired laparoscopically; the
      remaining lesions were repaired openly. Four patients underwent an open
      reoperation, and another patient needed five reoperations. There was one death
      (4.0%). CONCLUSIONS: Trocar and needle injuries are rare complications of
      laparoscopy. However, if not recognized intraoperatively and repaired
      immediately, they induce increased morbidity and mortality. Both open and closed
      establishment of the pneumoperitoneum are related to a potential danger of
      perforating lesions, but inserting the first trocar under direct vision allows
      early recognition and immediate repair.

PMID- 11344429
TI  - Intraoperative thermal regulation in patients undergoing laparoscopic vs open
      surgical procedures.
AB  - BACKGROUND: Although perioperative hypothermia is a well-known consequence of
      general anesthesia, it has been hypothesized that laparoscopic surgery
      exacerbates hypothermia to a greater extent than open surgery. The aim of this
      study was to demonstrate that laparoscopic surgery does not represent an
      increased risk for hypothermia. METHODS: A case-controlled retrospective study
      was conducted on 45 patients, 25 undergoing laparoscopic cholecystectomy and 20
      undergoing parathyroid surgery under endotracheal general anesthesia. Data were
      collected regarding age, sex, weight, height, American Society of
      Anesthesiologists (ASA) status, length of surgery, and anesthesia. In addition,
      we analyzed the type of intraoperative intravenous fluids, anesthetics and
      perioperative drugs, and temperature, blood pressure, and heart rate recordings
      during anesthesia. RESULTS: There was no significant difference between the two
      groups with respect to age, sex, body mass index (BMI), ASA status, type or
      amount of intravenous fluids infused, length of anesthesia or surgery, changes in
      mean blood pressure, or heart rate. Core body temperatures in both groups
      decreased significantly over time (p 0.05). There was no difference between the
      groups in terms of maximum drop in temperature (lowest temperature recorded vs
      baseline temperature) (1.1 +/- 0.7 vs 1.0 +/- 0.7 degrees C, p > 0.05).
      CONCLUSION: This study demonstrates that patients who undergo laparoscopic and
      open procedures of similar duration under endotracheal general anesthesia have
      similar profiles in terms of perioperative hypothermia.

PMID- 11344430
TI  - A comparison of laparoscopic supracervical hysterectomy vs laparoscopically
      assisted vaginal hysterectomy.
AB  - BACKGROUND: We set out to compare the length of stay, costs, and morbidity
      associated with laparoscopic supracervical hysterectomy (LSH) with
      laparoscopically assisted vaginal hysterectomy (LAVH). METHODS: We performed a
      cohort analysis of consecutive patients at a university-based medical center from
      April 1997 through October 1999. RESULTS: A total of 145 patients were identified
      initially; however, 13 cases were excluded because of concomitant procedures
      (retropubic urethropexy, lymphadenectomy, paravaginal repair). Of the 132
      patients included in the study, 27 underwent LSH and 105 underwent LAVH. The two
      groups were similar with respect to gravidity, parity, uterine weight, and
      preoperative diagnosis. Patients undergoing LSH had significantly shorter
      operating times (median, 181 vs 220 min, p = 0.007), briefer hospital stays
      (median, 1.0 vs 2.0 days, p = 0.0001), and less blood loss (median, 125 vs 400
      ml, p = 0.0001). None of the patients submitted to LSH experienced morbidity, as
      compared with a 13% morbidity rate for LAVH (bladder injury, n = 3; blood loss
      >1000 ml, n = 7; vaginal cuff hematoma, n = 4; 0% vs 13%; p = 0.04). CONCLUSIONS:
      Patients undergoing laparoscopic supracervical hysterectomy had shorter operating
      times, shorter hospital stays, and less morbidity than those who underwent
      laparoscopically assisted vaginal hysterectomy. The practice of routine
      cervicectomy at laparoscopic hysterectomy should be reconsidered.

PMID- 11344431
TI  - Laparoscopically assisted radical vaginal versus radical abdominal hysterectomy
      type II in patients with cervical cancer.
AB  - BACKGROUND: In a retrospective study, we compared a laparoscopic radical vaginal
      approach with abdominal radical hysterectomy type II for treatment of patients
      with cervical cancer at International Federation of Gynecology and Obstetrics
      (FIGO) stages I to III. METHODS: Between January 1991 and March 1994, 70 patients
      with cervical cancer were treated by radical abdominal hysterectomy, and between
      August 1994 and May 1999, 70 patients with cervical cancer were treated by
      laparoscopically assisted radical vaginal hysterectomy. Data from both the
      abdominal group and the laparoscopic-vaginal group were obtained retrospectively.
      RESULTS: The mean duration of surgery was significantly longer for the
      laparoscopic-vaginal approach than for the abdominal approach (292.9 vs 209.9
      min). Significantly more pelvic lymph nodes were removed by laparoscopy (27 vs
      10.7). Blood loss and transfusion rates were significantly lower in the
      laparoscopic-vaginal group. Intraoperative complications were seen more often
      during laparoscopic-vaginal surgery (p < 0.05). Early postoperative complications
      occurred significantly more frequently after the abdominal approach. The mean
      duration of hospital stay was significantly shorter for patients treated by
      laparoscopic-vaginal surgery (11.4 vs 22.8 days). CONCLUSION: Compared with
      laparotomy, the laparoscopic-vaginal approach for treatment of cervical cancer is
      associated with lower rates of transfusion and early postoperative morbidity.

PMID- 11344432
TI  - Three-port microlaparoscopic cholecystectomy in 159 patients.
AB  - BACKGROUND: Laparoscopic cholecystectomy has undergone many refinements including
      reductions in port size and number. This study attempts to determine whether
      further reduction in port size from that previously reported by us can reduce
      postoperative pain without compromising the efficacy of the surgery. METHODS: In
      this study, 159 patients underwent laparoscopic cholecystectomy with three ports:
      one 5-mm umbilical port, one 3-mm subxiphoid port, and one 3-mm port in the right
      subcostal position. Data were collected prospectively for each patient on the
      duration of analgesic use, quantity of analgesic tablets consumed, postoperative
      pain, most painful incision, and days of recovery required before return to
      activity and work. These measures were compared with those collected from a group
      of 100 patients who had undergone laparoscopic cholecystectomy with three 5-mm
      ports in a previous study. RESULTS: Patients in the current study group required
      analgesics for a longer duration (4 vs 2.9 days; p = 0.001), used more analgesic
      tablets (10.7 vs 8.1; p = 0.007), and reported greater postoperative discomfort
      (5 vs 4.1; p = 0.016) as compared with all in the 5-mm port group. The 3-mm port
      group needed more days for recovery before leaving the house (2.9 vs 2.7; p =
      0.504), but they returned to work earlier (5.1 vs 5.9; p = 0.065) than the group
      that had undergone cholecystectomy with three 5-mm ports, although there was not
      a significant difference between the groups. Operative time increased from 18.5
      to 20.9 min (p = 0.054) in the group with two 3-mm ports. Five patients (3.1%) in
      the current group required enlargement of a port to complete the procedure, as
      compared with none in the comparison group. There was one complication (0.6%), as
      compared with two complications (2.0%) in the previous group. CONCLUSIONS: This
      study did not demonstrate a reduction in postoperative pain or a consistent
      improvement in recovery when the port size was reduced at the subcostal and
      subxiphoid positions. It did, however, show that ports could safely be reduced in
      size without a negative impact on the surgeon's ability to perform a
      cholecystectomy. Reducing port size can be a tool in the surgeon's armamentarium
      for use in the attempt to optimize cosmetic results.

PMID- 11344433
TI  - Elective laparoscopic cholecystectomy: preoperative prediction of duration of
      surgery.
AB  - BACKGROUND: Efficient use of operating time has become a key concern. The aim of
      this study was to determine preoperative factors that can predict extended
      duration of operating time (>90 min) for laparoscopic cholecystectomy (LC).
      METHODS: Data collected prospectively on 827 consecutive patients who underwent
      elective LC between 1990 and 1997 were analyzed. Factors evaluated included age,
      gender; body mass index; comorbidity; duration of symptoms; history of jaundice,
      pancreatitis, or abdominal surgery; dilated common bile duct or thick-walled
      gallbladder on ultrasound; preoperative endoscopic retrograde
      cholangiopancreatography (ERCP) and endoscopic sphincterotomy (ES); and surgeon
      experience. Univariate and multivariate analyses were performed to identify
      factors predicting a long operation. RESULTS: Operating time was longer than 90
      min in 276 patients (33%). Predictors of extended operation time were age older
      than 55 years (odds ratio [OR] = 9.7), preoperative ES (OR = 2.8), and a thick
      walled gallbladder on ultrasound (OR = 2.5). CONCLUSION: These predictors may be
      useful in planning theater lists and anesthesia management, and in selecting
      patients for day surgery.

PMID- 11344434
TI  - Elective laparoscopic cholecystectomy.
AB  - BACKGROUND: Gallbladder stones are very common in patients with sickle cell
      disease and are the cause of recurrent abdominal pain. Their management has been
      highly controversial, especially for children. Nonoperated patients and those
      treated on an emergency basis have a very high rate of morbidity (>50%). METHODS:
      We performed a retrospective review of a series of 29 homozygous SS sickle cell
      children who underwent laparoscopic cholecystectomy between 1991 and April 1998.
      RESULTS: Only in one case a conversion was necessary (early in the series).
      Exploration of the common bile duct was done via intraoperative cholangiography.
      There were no mortalities. The morbidity rate was 17%; (however, of the five
      patients concerned, four suffered from hyperthermia for 2 days. All of the
      children were improved and enjoyed resolution of their abdominal pain.
      CONCLUSIONS: We believe that elective laparoscopic cholecystectomy at the
      earliest time possible, along with correct perioperative management, is the
      treatment of choice for cholelithiasis in children with sickle cell disease.

PMID- 11344435
TI  - Alterations in the immune system and tumor growth in laparoscopy.
AB  - BACKGROUND: The explosion in the use of therapeutic laparoscopy during the past
      decade has focused much research interest on finding a basic scientific support
      for the clinically apparent attenuation of the stress response to surgery. In
      particular, the potential impact that attenuation of the immune response to
      surgery may have on laparoscopy for the cure of malignancy has attracted much
      attention. METHODS: A review of the published literature on the stress response
      to laparoscopic surgery and the impact of laparoscopy on tumor growth was
      performed. RESULTS: Evidence favors an attenuation of the immune response to
      surgery with laparoscopic cholecystectomy. Whether this is true also of more
      major procedures such as laparoscopically assisted colectomy for malignancy is
      currently unclear. In animal models, tumor growth after laparoscopic surgery is
      less than after laparotomy and depends on the insufflation agent used.
      CONCLUSIONS: Laparoscopic cholecystectomy appears to be associated with
      attenuation of the immune response to surgery. The implications of these findings
      for the future use of laparoscopic surgical techniques for malignant disease
      remain unclear.

PMID- 11344436
TI  - CO2 environment influences the growth of cultured human cancer cells dependent on
      insufflation pressure.
AB  - BACKGROUND: Experimental and clinical studies, have suggested that the CO2
      pneumoperitoneum influences the development of intraabdominal tumor dissemination
      and port site metastases. Previous experiments performed both in vitro and in
      vivo have proved that CO2 insufflation stimulates malignant cell growth.
      Therefore, we designed a study to investigate the influence of CO2 insufflation
      administered at different pressures on the growth of cultured human tumor cells.
      METHODS: Two human tumor cell lines (CX-2 colon adenocarcinoma, DAN-G pancreas
      adenocarcinoma) were exposed to a CO2 environment maintained at different
      pressures (0 mmHg, 6 mmHg, 12 mmHg). Tumor growth was determined at different
      times after exposure to CO2 using fluorescence photometry. Cytotoxity of the CO2
      environment different pressures was investigated using flow cytometry. RESULTS:
      At 1-4 days after exposure to CO2 insufflation, CX-2 and DAN-G tumor cell growth
      was decreased significantly (p < 0.01). Proliferation of pancreatic
      adenocarcinoma DAN-G increased significantly from day 5 to day 15 independent of
      the insufflation pressure (p < 0.01). Proliferation of colon adenocarcinoma CX-2
      increased significantly from day 5 to day 15 but was found to be dependent on the
      insufflation pressure. CX-2 growth increased significantly with higher pressures
      (p < 0.05). CONCLUSION: CO2 insufflation influences the growth of cultured human
      tumor cells. After a short period of suppression, the CO2 environment stimulates
      malignant cell growth. The insufflation pressure may also have additional effects
      in promoting tumor growth.

PMID- 11344437
TI  - Delayed laparoscopy facilitates the management of biliary peritonitis in patients
      with complex liver injuries.
AB  - BACKGROUND: Nonoperative management is now regarded as the best alternative for
      the treatment of patients with complex blunt liver injuries. However, some
      patients still require surgical treatment for complications that were formerly
      managed with laparotomy and a combination of image-guided studies. METHODS: We
      reviewed the medical records of 15 patients who had complex blunt liver injuries
      that were managed nonoperatively and in which biliary peritonitis developed.
      RESULTS: Delayed laparoscopy was performed 2-9 days after admission in patients
      with extensive liver injuries. All 15 patients had developed local signs of
      peritonitis or a systemic inflammatory response. Laparoscopy was indicated to
      drain a large retained hemoperitoneum (eight patients), bile peritonitis (four
      patients), or an infected perihepatic collection (three patients). Laparoscopy
      was successful in all patients, and there was no need for further interventions.
      CONCLUSION: The data indicate that as more patients with complex liver injuries
      are treated nonoperatively and the criteria for nonoperative management continue
      to expand, more patients will need some type of interventional procedure to treat
      complications that historically were managed by laparotomy. At this point,
      laparoscopy is an excellent alternative that should become part of the
      armamentarium of the trauma surgeons who treat these patients.

PMID- 11344438
TI  - A modified laryngeal mask in the endoscopic management of an esophageal tumor.
AB  - The laryngeal mask airway (LMA) can be used for gastroscopy, but its use can
      result in loss of the seal and/or displacement of the cuff. We describe an LMA
      that was specifically modified for gastroscopy and report its use in a patient
      with an esophageal tumor. The modified LMA has (a) a second tube that allows
      instruments to be directed toward the esophagus and (b) a second cuff mounted on
      the dorsal surface that increases the efficacy of the seal with the larynx. A 78
      year-old man weighing 65 kg presented with a large mediastinal adenocarcinoma
      that was infiltrating the lateral wall of the thoracic esophagus. An
      esophagoscopy under anesthesia was planned to debulk the tumor. The modified LMA
      was inserted easily following induction with propofol. Anesthesia was maintained
      with propofol and 50% O2 in air and spontaneous ventilation. A lubricated 10.5-mm
      external diameter gastroscope was inserted into the second tube and passed easily
      into the esophagus. The tumor was successfully debulked using a polypectomy snare
      and an argon plasma coagulator. There was no loss of seal or displacement of the
      cuff, and the patient was stable throughout the procedure. We conclude that
      gastroscopy is feasible with the modified LMA. The device has a potential
      application in patients who require ventilatory support during gastroscopy.

PMID- 11344439
TI  - Thoracolaparoscopic repair of traumatic diaphragmatic rupture.
AB  - Diaphragmatic rupture may occur after blunt or penetration trauma caused by the
      application of a powerful external force. Diaphragmatic rupture usually is
      repaired via laporotomy and/or thoracotomy, depending on the associated organ
      injury. The case of a 49-year-old man with traumatic rupture of the left
      hemidiaphragm is presented. Preoperatively, diaphragmatic rupture with herniation
      of the stomach into the left thoracic cavity was confirmed by computed tomography
      scan of the thorax. Under thoracoscopic guidance, the stomach, spleen, and
      omentum were repositioned in the abdominal cavity, and the rupture site (10 cm)
      was closed by nonabsorbable suture. A subsequent laparoscopy was performed to
      assess the efficacy of the repair and the absence of any abdominal organ injury.
      The patient was discharged from hospital without any respiratory or abdominal
      symptoms. Our report confirms that in the case of a patient with penetration
      injuries to the lower chest and upper abdomen, a combined thoracoscopic and
      laparoscopic approach may offer both diagnostic and therapeutic benefits with
      reduced surgical trauma. We conclude that thoracoscopic repair of traumatic
      diaphragmatic rupture can be used safely when no abdominal organ injuries are
      found.

PMID- 11344440
TI  - The value of laparoscopy in the diagnosis and therapy of violin-string like
      perihepatic nonpostoperative adhesions.
AB  - We report three cases of Fitrz-Hugh Curtis syndrome (FHCs) that were diagnosed
      laparoscopically and showed microbiological or serological evidence of chlamydial
      infection. The case histories underscore the part played by abdominal right
      quadrant symptoms. In all three cases, right quadrant pain and tenderness
      constituted the presenting features. The patients were thought to have acute
      cholecystitis or acute appendicitis, but investigations proved negative.
      Laparoscopy was the key to the diagnosis, revealing the violin-string-like
      perihepatic adhesions typical of this syndrome. Lysis of the adhesions resolved
      the patients' symptoms of persistent severe abdominal pain. In the first case,
      the pain lessened dramatically only after the third operation, when the
      perihepatic adhesions were lysed. In the two other cases, the lysis was performed
      laparoscopically by fulguration and cutting. We consider this procedure to be an
      excellent therapeutic modality for the pain associated with FHCs.

PMID- 11344441
TI  - Laparoscopic lymph node staging of cervical cancer in the 19th week of pregnancy.
      A case report.
AB  - We present the case of a 39-year-old gravida I para 0 woman who underwent
      laparoscopic staging of lymph node involvement in cervical cancer in the 19th
      week of pregnancy. She had been diagnosed with adenosquamous carcinoma of the
      cervix, stage 1B1, grade 2, with tumor involvement of the lymphovascular space
      and tumor involved resection margins via a cone biopsy in the 16th week of
      pregnancy. In order to decide whether it would be safe to proceed with the
      pregnancy, she was submitted to the laparoscopic exposure and removal of 18
      parametric and pelvic lymph nodes. One positive lymph node was detected at the
      right internal iliac artery; therefore, an open radical hysterectomy with
      paraaortic lymphadenectomy was performed. This case shows that lymph node staging
      for cervical cancer can be done laparoscopically in the 2nd trimester.
      Information yielded during the course of this procedure can be crucial in
      deciding whether it is possible to preserve the pregnancy.

PMID- 11344442
TI  - Hand-assisted laparoscopic splenectomy for ruptured spleen.
AB  - Although the laparoscopic technique is an accepted method for elective
      splenectomy, it is controversial in the setting of trauma. A few reports have
      described laparoscopic splenorrhaphy for trauma, but none have performed
      laparoscopic splenectomy for splenic rupture. When the spleen is injured,
      vascular control and poor visibility due to bleeding present obstacles to
      laparoscopy. The development of the hand-assist device has helped surgeons make
      the transition from laparotomy to laparoscopy because of the advantages it
      provides, such as tactile sensation and immediate vascular control. We utilized
      these benefits of the hand-assist device to convert a laparoscopic operation to a
      hand-assisted laparoscopic operation and were thus able to avoid a laparotomy. We
      report a case in which the hand-assist device was used as an alternative to
      conversion during a laparoscopic splenectomy for ruptured spleen.

PMID- 11344443
TI  - Gas extravasation complicating laparoscopic extraperitoneal inguinal hernia
      repair.
AB  - Carbon dioxide can extravasate from the abdominal cavity during insufflation and
      result in pneumomediastinum, pneumothorax, and subcutaneous emphysema. We report
      a case of unilateral pneumothorax with pneumomediastinum and subcutaneous
      emphysema after laparoscopic extraperitoneal bilateral inguinal hernia repair.
      Additionally, we discuss the pathophysiology, diagnostic work-up, and management
      of this malady. Because of the natural resolution of CO2 pneumothoraces,
      observation for asymptomatic patients is appropriate, whereas tube thoracostomy
      should be reserved for symptomatic patients. It is utmost importance to determine
      the etiology of gas extravastion and consider other complications such as airway
      or esophageal injury or pulmonary barotrauma.

PMID- 11344444
TI  - Laparoscopically assisted pylorus-preserving gastrectomy.
AB  - BACKGROUND: The aim of this study was to describe the procedure of
      laparoscopically assisted pylorus-preserving gastrectomy (LAPPG), and to evaluate
      intra- and postoperative conditions of the patients. METHODS: We performed
      pylorus-preserving gastrectomy under laparoscopic observation, including regional
      lymph node dissection in early gastric cancer of the lower body. Seven patients
      were treated (two women and five men) using this procedure between April 1996 and
      April 1999. RESULTS: All the patients showed good postoperative recovery, and no
      signs of recurrence were recognized. There were no intraoperative or
      postoperative complications. Less pain, a rapid recovery, and good cosmetic
      results were noted. The patients exhibited little weight loss after surgery, and
      none demonstrated the dumping syndrome. Endoscopic examinations performed
      postoperatively did not indicate the presence of reflux gastritis or esophagitis.
      CONCLUSIONS: Our procedure of LAPPG may be useful for early gastric cancer,
      especially intramucosal cancer.

PMID- 11344445
TI  - The Ellik evacuator. A reinvention.

PMID- 11344446
TI  - Hand-assisted thoracoscopic esophagectomy using a new supportive approach.

PMID- 11344448
TI  - An automatic system for the assessment of complex medium additives under
      cultivation conditions.
AB  - Complex medium additives such as yeast extract or peptone are often used in
      industrial cell culture processes to prolong cell growth and/or to improve
      product formation. The quality of those supplements is dependent on the
      preparation method and can differ from lot to lot. To guarantee consistent
      production these different lots have to be tested prior to use in fermentation
      processes. Because a detailed qualitative and quantitative analysis of all
      components of such a complex mixture is a very difficult task, another assessment
      method has to be chosen. The best way to evaluate the effect of such supplements
      is to monitor cell activity during real cultivation conditions with and without
      the added supplement lot. A bioreactor-based test system has been developed to
      determine the oxygen requirement of the cells as a response to the addition of a
      supplement to be tested under standardized conditions. Investigations were
      performed with a mouse-mouse hybridoma cell line and yeast extracts as an example
      for complex medium additives. The results showed differences in the impact
      between different extract lots and between different concentrations of an
      extract.

PMID- 11344449
TI  - Production of different morphologies of biocompatible polymeric materials by
      supercritical CO(2) antisolvent techniques.
AB  - High-value biocompatible-polymers have been processed with supercritical
      antisolvent techniques to produce solid structures of different shape and size.
      In particular, a class of hyaluronic acid-derived polymers (Hyaff11-p100, Hyaff11
      p80, Hyaff11-p75, Hyaff 302) have been used to obtain various morphologies such
      as microspheres, threads, fibers, networks, and sponges. The effect of
      thermodynamic variables on precipitation were highlighted in some preliminary
      batch experiments. Then, different products were obtained by tuning the values of
      operating parameters. Threads and fibers were the result of a continuous
      supercritical antisolvent (SAS) process where a concentrated polymer solution was
      pumped through a micrometric nozzle: The threads showed a reticular internal
      structure with an adjustable type of cavity. For production of networks and
      sponges, the concentration of polymer plays the key role. Below a critical value
      it was not possible to obtain a continuous network, while above it, a structure
      similar to that of the natural bone with three types of internal microporosity
      were obtained. Again, by tuning pressure and polymer concentration, the internal
      porosity could be controlled. Microparticles were also produced by the SAS
      process, and a control of their morphology was achieved by varying the
      concentration of the polymer in the starting solution and the density of organic
      solvent-CO(2) mixtures. All the products obtained by SAS have negligible content
      of residual solvent. A qualitative interpretation of experimental results is
      presented.

PMID- 11344450
TI  - Metabolic flux modeling of detoxification of acetic acid by Ralstonia eutropha at
      slightly alkaline pH levels.
AB  - Ralstonia eutropha grows on and produces polyhydroxyalkanoates (PHAs) from
      fermentation acids. Acetic acid, one major organic acid from acidogenesis of
      organic wastes, has an inhibitory effect on the bacterium at slightly alkaline pH
      (6 g HAc/L at pH 8). The tolerance of R. eutropha to acetate, however, was
      increased significantly up to 15 g/L at the slightly alkaline pH level with high
      cell mass concentration. A metabolic cell model with five fluxes is proposed to
      depict the detoxification mechanism including mass transfer and acetyl-CoA
      formation of acetic acid and the formation of three final metabolic products,
      polyhydroxybutyrate (PHB), active biomass, and CO(2). The fluxes were measured
      under different conditions such as cell mass concentration, acetic acid
      concentration, and medium composition. The experimental results indicate that the
      acetate detoxification by high cell mass concentration is attributed to the
      increased fluxes at high extracellular acetate concentrations. The fluxes could
      be doubled to reduce and hence detoxify the accumulated intracellular acetate
      anions.

PMID- 11344447
TI  - Alteration of lipase chain length specificity in the hydrolysis of esters by
      random mutagenesis.
AB  - The feasibility of altering the chain length specificity of industrially
      important Rhizomucor miehei lipase was investigated by randomly mutating Phe94 in
      the protein groove which is responsible for accommodating the acyl chain of the
      substrate. The recombinant lipase was initially expressed in E. coli. Individual
      colonies were selected, grown, and the DNA sequence of the lipase gene
      determined. Fourteen of the 19 possible mutants were identified and each of these
      was transformed into Pichia pastoris which expresses the enzyme extracellularly.
      The yeast was grown and the supernatants assessed in several assays with long and
      short chain substrates. Based on this preliminary screen, one mutant, Phe94Gly,
      was selected and purified to homogeneity for further analysis. It was found that
      the substitution of phenylalanine 94 with glycine led to an enzyme which was
      about six times less active against resorufin ester but displayed 3-4 times
      higher activity with short chain substrates such as butyric acid esters. The
      observed alteration to the enzyme specificity was rationalised using the
      available 3D structure of the lipase.

PMID- 11344451
TI  - Purification of recombinant cutinase by extraction in an aqueous two-phase system
      facilitated by a fatty acid substrate.
AB  - Purification of recombinant wild-type cutinase from the culture supernatant of
      Saccharomyces cerevisiae by extraction in aqueous two-phase system was
      investigated. The partition of the enzyme in a polyethylene glycol (PEG)
      potassium phosphate system to the top phase was increased with lower molecular
      weight PEG. Enzyme partition in a 20% PEG/15% phosphate two-phase system was
      studied in the presence of detergents, fatty acids, and alcohols, respectively.
      Addition of 0.5% (w/w) butyrate increased the partition coefficient from 17 to
      135 and the purification factor from 10 to 23. The effect of butyrate was also
      confirmed by using the countercurrent mode of extraction. Recovery of cutinase
      from the top phase was achieved by a secondary extraction into a new salt phase
      at a lower pH or a lower temperature. A specific interaction of butyrate to the
      active site of the enzyme was demonstrated by fluorescence spectroscopy. Size
      exclusion chromatography showed the cutinase-butyrate complex to be over two
      times the size of the free enzyme.

PMID- 11344452
TI  - Enhanced selection of an anaerobic pentachlorophenol-degrading consortium.
AB  - A rapid enrichment approach based on a pentachlorophenol (PCP) feeding strategy
      which linked the PCP loading rate to methane production was applied to an upflow
      anaerobic sludge bed reactor inoculated with anaerobic sludge. Due to this
      strategy, over a 140-day experimental period the PCP volumetric load increased
      from 2 to 65 mg L(R)(-1) day(-1) with a near zero effluent concentration of PCP.
      Dechlorination dynamics featured sequential appearance of 3,4,5-chlorophenol, 3,5
      chloro- phenol, and 3-chlorophenol in the reactor effluent. Profiling of the
      reactor population by denaturing gradient gel electrophoresis (DGGE) revealed a
      correlation between the appearance of dechlorination intermediates and bands on
      the DGGE profile. Nucleotide sequencing of newly detected 16S rDNA fragments
      suggested the proliferation of Clostridium and Syntrophobacter/Syntrophomonas
      spp. in the reactor during PCP degradation. Published by John Wiley & Sons, Inc.

PMID- 11344453
TI  - DegP-coexpression minimizes inclusion-body formation upon overproduction of
      recombinant penicillin acylase in Escherichia coli.
AB  - We demonstrated the enhancement of recombinant penicillin acylase (PAC)
      production in Escherichia coli by increasing the intracellular concentration of
      the periplasmic protease DegP. Using appropriate host/vector systems (e.g., HB101
      harboring pTrcKnPAC2902 or MDDeltaP7 harboring pTrcKnPAC2902) in which the
      expression of the pac gene was regulated by the strong trc promoter, the
      overproduction of PAC was often limited by periplasmic processing and inclusion
      bodies composed of protein aggregates of PAC precursors were formed in the
      periplasm. The amount of these periplasmic inclusion bodies was significantly
      reduced and PAC activity was significantly increased upon coexpression of DegP.
      The specific PAC activity reached an extremely high level of 674 U/L/OD(600) for
      MDDeltaP7 harboring pTrcKnPAC2902 and pKS12 under optimum culture conditions.
      However, such improvement in the production of PAC was not observed for the
      expression systems (e.g., MDDeltaP7 harboring pCLL2902) in which the periplasmic
      processing was not the step limiting the production of PAC. The results suggest
      that DegP could in vivo assist the periplasmic processing though the enzyme is
      shown to be not absolutely required for the formation of active PAC in E. coli.
      In addition, the steps limiting the production of PAC are identified and the
      reasons for the formation of PAC inclusion bodies are discussed here.

PMID- 11344454
TI  - Efficient preparation of (R)-alpha-monobenzoyl glycerol by lipase catalyzed
      asymmetric esterification: optimization and operation in packed bed reactor.
AB  - Optically active (R)-alpha-monobenzoyl glycerol (MBG) was synthesized by Candida
      antarctica lipase B (CHIRAZYME L-2) catalyzed asymmetric esterification of
      glycerol with benzoic anhydride in organic solvents. Various conditions, such as
      the type and composition of the organic solvent, water content of the system,
      reaction temperature, and concentrations of the substrates were systematically
      examined and optimized in screw-capped test tubes with respect to both the
      reaction rate and the enzyme selectivity. 1,4-Dioxane was found to be the best
      solvent and no additional water was needed for the system. The optimum
      temperature was around 30 degrees C, while the most suitable substrate
      concentrations were 100 mM each for glycerol and benzoic anhydride, respectively.
      However, when excessive anhydride (e.g., 200 mM) was used, the produced MBG could
      be further transformed into 1,3-dibenzoyl glycerol (DBG) by the same enzyme with
      a priority to (S)-MBG, resulting in a significant improvement of the product
      optical purity from ca. 50-70% e.e. Under optimal conditions (100 mM glycerol,
      100-200 mM benzoic anhydride, dioxane, 25-30 degrees C), the enzymatic synthesis
      of (R)-MBG was successfully operated in a packed-bed reactor for about 1 week,
      with an average productivity of 0.79 g MBG/day/g biocatalyst in the case of
      continuous operation and 0.94 g MBG/day/g biocatalyst in the case of
      semicontinuous operation. After refinement and preferential crystallization of
      the crude product, (R)-MBG could be obtained in an almost optically pure form
      (>98% e.e.).

PMID- 11344455
TI  - Limited adhesion of biodegradable microspheres to E- and P-selectin under flow.
AB  - In a variety of disease settings the expression of the endothelial selectins E-
      and P-selectin appears to be increased. This feature makes these molecules
      attractive targets around which to design directed drug-delivery schemes. One
      possible approach for achieving such delivery is to use polymeric biodegradable
      microspheres bearing a humanized monoclonal antibody (MAb) for E- and P-selectin,
      MAb HuEP5C7.g2. Perhaps the simplest technique for "coupling" HuEP5C7.g2 to the
      microspheres is via nonspecific adsorption. Previous studies suggest, however,
      that the adsorption of proteins onto microspheres fabricated in the presence of a
      stabilizer such as poly(vinyl alcohol) (PVA) is limited. It is unclear to what
      extent this limited level of adsorbed HuEP5C7.g2 would be able to support
      adhesion to E- and P-selectin under flow conditions. To explore this issue, we
      prepared microspheres from the biodegradable polymer, poly(epsilon-caprolactone)
      (PCL), using a single emulsion process and PVA as a stabilizer. We then incubated
      the PCL microspheres with HuEP5C7.g2 and studied the adhesion of the resulting
      HuEP5C7.g2 microspheres to E- and P-selectin under in vitro flow conditions. We
      found that the HuEP5C7.g2 PCL microspheres exhibit specific adhesion to Chinese
      hamster ovary cells stably expressing P-selectin (CHO-P) and 4-h IL-1beta
      activated human umbilical vein endothelial cells (HUVEC). In contrast, HuEP5C7.g2
      PCL microspheres exhibit little adhesion to parental CHO cells or unactivated
      HUVEC. The attachment efficiency to the selectin substrates was quite low, with
      appreciable attachment occurring only at low shear (0.3 dyn/cm(2)). Other
      supporting data strongly suggest that the limited attachment efficiency is due to
      a low level of HuEP5C7.g2 adsorbed to the PCL microspheres. Although the
      attachment was limited, a significant percentage of the HuEP5C7.g2 PCL
      microspheres were able to remain adherent at relatively high shear (8 dyn/cm(2)).
      Combined, our data suggest that HuEP5C7.g2 PCL microspheres exhibit selective
      limited adhesion to cellular substrate expressing E- and P-selectin.

PMID- 11344456
TI  - Engineering temperature-sensitive poly(N-isopropylacrylamide) polymers as
      carriers of therapeutic proteins.
AB  - This study was carried out to engineer N-isopropylacrylamide (NiPAM) polymers
      that contain protein-reactive N-acryloxysuccinimide (NASI) and hydrophobic
      alkylmethacrylates (AMAs). These thermoreversible, protein-conjugating polymers
      hold potential for retention of therapeutic proteins at an application site where
      tissue regeneration is desired. The lower critical solution temperatures (LCST)
      of the polymers were effectively controlled by the AMA mole content. The AMAs
      with longer side-chains were more effective in lowering the LCST. Polymers
      without NASI exhibited a stable LCST in phosphate buffer and in serum over a 10
      day study period. The LCST of polymers containing NASI was found to increase over
      time in phosphate buffer, but not in serum-containing medium. The LCST increase
      in phosphate buffer was proportional to the AMA content. The feasibility of
      localizing a therapeutic protein, recombinant human bone morphogenetic protein-2
      (rhBMP-2), to a site of application was explored in a rat intramuscular injection
      model. The results indicated that polymers capable of conjugating to rhBMP-2 were
      most effective in localizing the protein irrespective of the LCST (13-25 degrees
      C). For polymers with no NASI groups, a lower LCST resulted in a better rhBMP-2
      localization. We conclude that thermosensitive polymers can be engineered for
      delivery of therapeutic proteins to improve their therapeutic efficacy.

PMID- 11344457
TI  - Isolation of a recombinant antibody from cell culture supernatant: continuous
      annular versus batch and expanded-bed chromatography.
AB  - Annular chromatography represents a crossflow approach to chromatographic
      separations, that allows the continuous separation of multicomponent mixtures.
      The potential of the method for continuous bioseparation has been discussed for
      some time, however, we demonstrate for the first time the processing of a complex
      feed (cell culture supernatant) taken from an actual (bio)process. Moreover,
      while previously published applications of annular chromatography concentrated on
      noninteractive (gel filtration) or nonspecific (ion exchange) chromatography, we
      show the possibility of continuous annular affinity chromatography. In
      particular, a commercially available preparative continuous annular
      chromatography (P-CAC) system was used to purify a recombinant antibody (human
      IgG(1)-kappa) from CHO cell culture supernatants by (pseudo)affinity
      chromatography on hydroxyapatite (HA) and rProtein A. Methods developed using
      small (2 mL) batch columns could be directly transferred to the P-CAC, where they
      yielded similar results in terms of final product quality. Yields were between
      87% and 92% in the case of HA and between 77% and 82% in the case of rProtein A
      chromatography. DNA removal was nearly quantitative in all cases. Concomitantly,
      the antibody fraction of the total protein content was raised by one order of
      magnitude in HA and by a factor of 50 by rProtein A chromatography. In addition,
      a novel HA material (particle diameter -120 microm) was investigated, which was
      compatible with expanded-bed applications. However, the final purity of the
      antibody thus obtained and also the yields (<70%) were less than satisfactory.

PMID- 11344458
TI  - Determination of 3-deoxy-D-arabino-heptulosonate 7-phosphate productivity and
      yield from glucose in Escherichia coli devoid of the glucose phosphotransferase
      transport system.
AB  - The effect of inactivation of the glucose phosphotransferase transport system
      (PTS) on 3-deoxy-D-arabino-heptulosonate 7-phosphate (DAHP) productivity and
      yield from glucose in Escherichia coli is reported. Strains used in this study
      were the PTS(+) PB103 and its PTS(-) glucose(+) derivative NF9. Their aroB(-)
      derivatives PB103B and NF9B were constructed to allow accurate measurement of
      total carbon flow into the aromatic pathway. The measured specific rates of DAHP
      synthesis were 0.55 and 0.94 mmol/g-dcw. h and the DAHP molar yields from glucose
      were 0.43 and 0.71 mol/mol for the PTS(+) aroB(-)and the PTS(-) glucose(+) aroB(
      )strains, respectively. For the latter strain, this value represents 83% of the
      maximum theoretical yield for DAHP synthesis from glucose.

PMID- 11344459
TI  - Compulsive checking behaviors in generalized anxiety disorder.
AB  - Recent evidence suggests that a relationship exists between worry, the central
      feature of generalized anxiety disorder (GAD), and compulsive behaviors,
      particularly compulsive checking. In this article we report the results from two
      studies. The first study assessed the frequency of obsessions and compulsions in
      107 principally diagnosed GAD clients. The second study examined levels of
      alexithymia in analogue samples of GAD checkers (n = 31), GAD noncheckers (n =
      30), and non-GAD nonchecking controls (n = 27) using the Toronto Alexithymia
      Scale-20 (Bagby, Parker, & Taylor, 1994). The results from these studies suggest
      that compulsive behaviors in the form of compulsive checking is more common in
      GAD than previously expected and that such behaviors in GAD may act as an
      additional mechanism by which affective experiences are avoided.

PMID- 11344460
TI  - Current status of doctoral-level training in psychological testing.
AB  - Training directors of 82 American Psychological Association (APA)-approved
      doctoral programs in clinical psychology responded to a survey on the current
      status and recent changes in doctoral training in psychological assessment.
      Although testing continues to be a major focus of training, a slight decline in
      emphasis on assessment was noted, most notably with projective techniques. With
      few exceptions (e.g., NEO-PI, Personality Assessment Inventory), traditional
      tests were emphasized in coursework and also were considered "essential" for the
      practicing psychologist. Interestingly, there seems to be increased emphasis on
      the interview and neuropsychological testing compared to prior surveys of
      academic settings. Only 29% of the training directors reported that their
      programs have been significantly affected by managed care, suggesting that most
      academic programs are somewhat insulated from marketplace pressures. It is
      recommended that training programs balance their focus on traditional academic
      values with the realities of the clinical practice arena.

PMID- 11344461
TI  - Computerized psychological test usage in APA-accredited training programs.
AB  - Despite the advantages of computerized psychological assessment and the
      proliferation of assessment software, many psychologists still do not use
      computerized assessment, and its utilization has not increased during the past
      decade. Two-hundred-fifty-one APA-accredited training programs in clinical and
      counseling psychology were surveyed concerning their use of computerized
      psychological assessment. Directors reported a median of only three computerized
      tests used in their training programs. Twenty-five percent of the respondents
      reported no computerized psychological tests in their training programs. The
      computerized tests most-often used in psychology programs were compared to
      results of surveys of psychological tests most-often used in clinical practice.

PMID- 11344463
TI  - Underlying cognitions in the selection of lottery tickets.
AB  - There is evidence that the faulty cognitions underlying an individual's playing
      behavior maintains and supports their gambling behavior. Sixty undergraduate
      students completed the South Oaks Gambling Screen (SOGS), a measure to assess
      pathological gambling, and a questionnaire ascertaining the type and frequency of
      their gambling activities. Sixteen Loto 6/49 tickets were presented to
      participants and ranked according to their perceived likelihood of being the
      winning ticket. The numbers on the tickets were categorized as: long sequences
      (e.g., 1-2-3-4-5-6), patterns and series in a pseudo-psychological order (e.g.,
      16-21-26-31-36-41), unbalanced (e.g., six numbers from 1-24 or 25-49), and those
      appearing to be random (e.g., 11-14-20-29-37-43). Verbal protocols of ticket
      selections were ranked into eight heuristics. Results revealed that for the
      entire sample the greatest percentage of tickets chosen for the first four
      selections were "random" tickets. Further, the most commonly cited reason for
      selecting and changing a lottery ticket was perceived randomness. The results are
      discussed with reference to the cognitions used when purchasing lottery tickets.

PMID- 11344462
TI  - Ethical beliefs of mental-health professionals and undergraduates regarding
      therapist practices.
AB  - Psychotherapists should be aware of any discrepancies of opinion between
      themselves and those outside the mental-health profession regarding the
      ethicality of therapist actions. In this study, the beliefs of mental-health
      professionals and nonprofessionals (represented by undergraduate students)
      regarding the ethicality of therapist behaviors were compared. Factor analysis of
      82 specific therapist behaviors yielded three factors: nonsexual dual
      relationships, assertive or discomforting therapist actions, and sexual dual
      relationships. A comparison of factor composite scores indicated that
      undergraduates, in relation to professionals, rated nonsexual dual relationships
      as more ethical and assertive or discomforting actions as less ethical. Although
      these effects may diminish with age, these results nonetheless suggest that
      mental-health professionals may hold ethical beliefs that are inconsistent with
      those who seek their services. Implications of these findings are discussed.

PMID- 11344464
TI  - An examination of the psychometric structure of the Multidimensional Pain
      Inventory.
AB  - Factor analyses to create the Multidimensional Pain Inventory (MPI) warrant
      further examination due to small sample size, the use of separate factor analyses
      for each MPI section, and lack of evidence for the replicability of the factor
      model. The present study randomly assigned 972 respondents to one of three
      samples. Study 1 used data from Sample 1 (n = 452) to examine the replicability
      of the MPI factor structure reported by Kerns, Turk, and Rudy (1985), and to
      measure the internal consistencies of MPI scales. In Study 2, confirmatory factor
      analyses using Sample 2 data (n = 267) verified a revised MPI factor structure
      that was generated in Study 1; cross-validation was achieved using data from
      Sample 3 (n = 253). The revised MPI model differed from the original model in its
      number of scales and pattern of scale loadings. Recommendations for the
      refinement of the MPI are proposed.

PMID- 11344465
TI  - Factor structure and psychometric properties of the brief Mizes Anorectic
      Cognitions questionnaire.
AB  - The Mizes Anorectic Cognitions-Revised (MAC-R) questionnaire is a 24-item self
      report instrument designed to assess cognitions associated with anorexia and
      bulimia nervosa. We examined the factor structure and psychometric properties of
      the MAC-R in a sample of 290 undergraduates. We found that a brief 3-factor
      oblique model (composed of 12 items) of the MAC-R provided acceptable fit to the
      present sample data. This model was largely invariant across male and female
      participants. The brief version of the MAC-R (the BMAC) and subscale scores
      correlated significantly with scores from related measures of eating disorders,
      showing evidence of concurrent validity. The BMAC total and subscales also showed
      evidence of discriminant validity by differentiating between empirically defined
      subclinical eating disorders and control participants. Both logistic regression
      and discriminant function analyses showed that only the self-control and self
      esteem subscale was most useful in distinguishing between the subgroups.

PMID- 11344466
TI  - Discriminative validity of the MacAndrew Alcoholism Scale with Cluster B
      personality disorders.
AB  - This study was designed to assess the ability of the Minnesota Multiphasic
      Personality Inventory (MMPI-2) MacAndrew Alcoholism Scale (MAC-R) to
      differentiate between outpatients with personality disorders with Substance
      Related Disorders (SRDs) and without SRDs. MMPI-2 validity, clinical, and MAC-R
      scale scores were compared in an SRD Cluster B group (comprised of Narcissistic,
      Antisocial, Borderline, and Histrionic; n = 15), a non-SRD Cluster B group (n =
      33), and a non-SRD group with personality disorders from Clusters A and C (n =
      18). Results revealed that the substance-abusing Cluster B group scored
      significantly higher on the MAC-R ( p <.0001) as well as the Psychopathic Deviate
      scale ( p <.01). Dimensional analyses illustrated that MAC-R scores were related
      to the presence of an SRD diagnosis (rpb =.70, p <.0001) and diagnostic criteria
      for Antisocial Personality Disorder (r =.60, p <.0001). Stepwise regression
      revealed that (in order of magnitude) the presence of a substance-abuse diagnosis
      followed by diagnostic criteria for Antisocial and Histrionic Personality
      Disorders were most related to MAC-R scores (R =.78, R(2) =.60). This indicates
      that the MAC-R may be more related to the presence of an SRD than has been
      suggested, and when used in outpatient settings as MacAndrew (1965) intended, the
      MAC-R may be useful as a screening device for assessing SRD among outpatients
      with Axis II psychopathology.

PMID- 11344467
TI  - Psychometric properties of an Italian version of the Barratt Impulsiveness Scale
      11 (BIS-11) in nonclinical subjects.
AB  - To assess the psychometric properties of the Italian translation of the Barratt
      Impulsiveness Scale-11 (BIS-11), the scale was administered to 763 college
      undergraduates. Based on analyses using item-total correlations and t-tests for
      differences between the top and the bottom total score quartiles, all items from
      the English version of the BIS-11 were retained in the Italian version.
      Cronbach's alpha for internal consistency was.79 and two-month test-retest
      reliability was.89. An exploratory principal-components analysis replicated the
      six first-order factors and three oblique second-order factors, consistent with
      the number identified in the English version. However, subfactor item loadings
      differed between the English and Italian versions. The overall item pool was
      consistent in being a homogeneous measure of impulsiveness. The BIS-11 total
      score was correlated significantly with aggression and ADHD measures. The BIS-11
      also significantly differentiated between high and low levels of binge eating,
      alcohol consumption, and cigarette smoking.

PMID- 11344468
TI  - Naming and verbal memory skills in adults with Attention Deficit Hyperactivity
      Disorder and Reading Disability.
AB  - Research suggests that children with Attention Deficit Hyperactivity Disorder
      (ADHD) and Reading Disability (RD) can be differentiated based on their
      performance on measures of naming and verbal memory. It is not known whether this
      same pattern characterizes adults with these disorders. In this study, adults
      with and without ADHD and RD were compared on naming and verbal memory abilities.
      Results did not support the hypothesis that adults with ADHD and RD are
      significantly different from each other, or from a contrast group, on naming and
      verbal memory measures after controlling for Full-Scale IQ (FSIQ). These results
      were replicated across two sets of classification criteria used to identify
      diagnostic groups. Factors that could account for the inconsistency in research
      findings with children and adult subjects are discussed.

PMID- 11344469
TI  - Zen meditation and ABC relaxation theory: an exploration of relaxation states,
      beliefs, dispositions, and motivations.
AB  - This study is an attempt to rigorously map the psychological effects of Zen
      meditation among experienced practitioners. Fifty-nine Zen meditators with at
      least six years of experience practiced an hour of traditional Zazen seated
      meditation. A control group of 24 college students spent 60 min silently reading
      popular magazines. Before relaxation, all participants took the Smith Relaxation
      States Inventory (SRSI), the Smith Relaxation Dispositions/Motivations Inventory
      (SRD/MI), and the Smith Relaxation Beliefs Inventory (SRBI). After practice,
      participants again took the SRSI. Analyses revealed that meditators are less
      likely to believe in God, more likely to believe in Inner Wisdom, and more likely
      to display the relaxation dispositions Mental Quiet, Mental Relaxation, and
      Timeless/Boundless/Infinite. Pre- and postsession analyses revealed that
      meditators showed greater increments in the relaxation states Mental Quiet, Love
      and Thankfulness, and Prayerfulness, as well as reduced Worry. Results support
      Smith's ABC Relaxation Theory.

PMID- 11344470
TI  - Medical student cancer education: experience from projects in Sao Paulo, Brazil,
      and in other parts of Latin America.

PMID- 11344472
TI  - Combination technique for sentinel node mapping in breast cancer.

PMID- 11344473
TI  - Soft tissue sarcomas involving the pelvis.
AB  - BACKGROUND AND OBJECTIVES: Soft tissue sarcomas (STS) of the true pelvis are rare
      tumors and there is little information in the literature related to pelvic STS.
      The purposes of this review were to understand the anatomic extension of these
      tumors to better plan surgical treatment and to determine the outcome of these
      patients. METHODS: Eighteen consecutive patients presenting between 1987 and 1995
      with soft tissue sarcomas involving the true pelvis were retrospectively reviewed
      at minimum follow-up of 18 months. Cross-sectional imaging was reviewed for each
      patient to determine the anatomical location of the lesions. RESULTS: The tumors
      were confined to the true pelvis in 4 patients, extended to the retroperitoneum
      in three cases, and extended to the thigh in 11 patients. Adjuvant radiation was
      administered to all but 2 patients who had received radiation to the region in
      the past and all patients underwent surgical resection (local resection in 13
      patients and hindquarter amputation in 5 patients). Surgical resection had a high
      rate of morbidity and complications including positive resection margins in nine
      individuals. Of the 18 patients, 11 died at a mean time of 15.5 (2-58) months
      from surgery, 4 were alive with evidence of disease at a mean time of 44.3 (18
      68) months, and 3 were alive with no evidence of disease at a mean time of 57 (43
      71) months. CONCLUSIONS: Soft tissue sarcoma of the pelvis is fortunately a rare
      disease with a high risk of local and systemic disease progression despite
      treatment with irradiation and surgical resection.

PMID- 11344475
TI  - Clear cell sarcoma: the Roswell Park experience.
AB  - BACKGROUND AND OBJECTIVES: Clear cell sarcoma of the tendons and aponeuroses
      (CCSTA) is an aggressive, rare soft-tissue tumor with approximately 300 reported
      cases. Although it appears to be histogenetically related to melanoma, its
      clinical behavior resembles soft tissue sarcoma with a propensity for lymph node
      metastases. We report our experience at a tertiary cancer center. METHODS: Eight
      cases of CCSTA evaluated at Roswell Park Cancer Institute between 1970 and 1998
      were reviewed retrospectively. Patient data analyzed included patient age,
      gender, anatomic location, size of tumor, development of local, regional and
      distant recurrence, and patient status at last follow up. RESULTS: Six of eight
      patients were alive at 2 years, while three of seven patients were alive at 5
      years. Of the patients alive with no evidence of recurrence, two had tumors of
      less than 2 cm, and the remaining patient had incomplete information regarding
      tumor size. Five patients recurred within 2 years of definitive surgical
      management. Four had tumors > 5 cm. All five patients progressed to metastatic
      disease at a median follow up of 20 months (range 1-108 months) following
      definitive surgical management and all eventually died of their disease at a
      median of 3 months (range 0-24 months) from presentation with metastatic disease.
      Four of five patients with lesions > 5 cm received adjuvant chemotherapy with
      intent to cure, but all eventually died of disease at 4, 22, 34, and 41 months
      from initial presentation. CONCLUSIONS: CCSTA is an aggressive tumor of the soft
      tissues. Early recognition and management are associated with an excellent long
      term prognosis. Tumors greater than 5 cm warrant aggressive surgical management
      and treatment, and are at high risk of the development of distant disease.
      Aggressive multiagent chemotherapy appeared to have no impact on outcome. Other
      adjuvant therapeutic options including immunotherapy should be investigated.

PMID- 11344476
TI  - Preoperative lymphoscintigraphy and sentinel lymph node biopsy in papillary
      thyroid cancer. A pilot study.
AB  - BACKGROUND AND OBJECTIVES: Lymphadenectomy for papillary thyroid cancer is a
      matter of debate. After showing its usefulness as a prognostic factor in both
      melanoma and breast cancer, the concept of sentinel lymph node biopsy was also
      recently applied to differentiated thyroid cancer. To date, all attempts to
      locate and remove the sentinel node were based on the intraoperative injection of
      a vital dye. The feasibility and the technical details of using preoperative
      lymphoscintigraphy coupled with intraoperative vital dye and gamma probe scanning
      were investigated and discussed. METHODS: Six patients diagnosed with papillary
      thyroid cancer were submitted to preoperative lymphoscintigraphy with (99m)Tc
      labelled colloidal albumin at different dosages. The operation consisted in a
      total thyroidectomy with sentinel lymph node biopsy guided by intraoperative
      injection of a vital dye (Blu Patent V, 2.5%) and scanning with a hand-held gamma
      probe. Lymph node dissection was completed in the area in which the sentinel node
      was located. RESULTS: The sentinel node was identified using all the three
      methods in all cases (100%). Considering one of the methods alone, identification
      rates were 66, 50, and 83% for preoperative lymphoscintigraphy, vital dye, and
      probe scanning, respectively. One sentinel node was identified in four cases and
      two in the other two cases. The optimal dosage of the tracer appeared to be at 22
      MBq. CONCLUSIONS: These results underline the necessity to use the combination of
      nuclear medicine imaging and lymphatic vital dye in order to enhance the
      identification rate of sentinel node also in thyroid cancer. It is now necessary
      to check the diagnostic accuracy of this procedure through a controlled trial
      involving a more extended lymph node dissection in the neck.

PMID- 11344478
TI  - Reconstruction of the pancreatic duct after pancreaticoduodenectomy: a
      modification of the Whipple procedure.
AB  - BACKGROUND AND OBJECTIVES: Pancreaticoduodenectomy is still associated with high
      morbidity and mortality even though there has been significant progress in the
      field of pancreatic surgery and postoperative follow-up. The pancreatoenteric
      anastomosis, regardless of the technique used, is a major cause for both
      morbidity and mortality after Whipple procedure. To overcome all problems
      resulting from anastomotic leakage, we used external drainage of the pancreatic
      duct. METHODS: In 24 patients who underwent pancreaticoduodenectomy in our
      Department from 1986 to 1995, a modification to the standard Whipple procedure
      was performed. Instead of pancreaticoenteric anastomosis, external drainage of
      the pancreatic duct remnant was performed. The pancreatic duct was intubated with
      a silastic tube, the external end of which was sutured to the skin. All patients
      received substitution therapy with pancreatic enzymes. RESULTS: Mortality in our
      group of patients was 4%. No complications due to the external drainage of the
      pancreatic duct were reported, while no patient developed diabetes mellitus after
      surgery. CONCLUSIONS: External drainage of the pancreatic duct remnant can be
      used alternatively to pancreatoenteric anastomosis after pancreatoduodenectomy.
      The technique is safe and simple to perform and appears to reduce overall
      operative time. It may be an option for patients with significant comorbidity
      and/or intraoperative hemodynamic instability which mandates expeditious
      completion of the operation.

PMID- 11344480
TI  - Differences in estrogen receptor status, HER2, and p53 comparing metachronous
      bilateral breast carcinoma.
AB  - BACKGROUND AND OBJECTIVES: We analyzed the clinicopathologic characteristics and
      tumor biology of metachronous bilateral breast carcinoma with regard to p53, HER2
      and hormone receptor status. METHODS: A consecutive series of 54 female
      metachronous bilateral breast carcinoma patients treated at the National Cancer
      Center Hospital between 1980 and 1997 were the primary source of these
      retrospective data. Clinicopathologic background factors were analyzed, and
      immunohistochemical staining for p53, HER2, and hormone receptor status was
      carried out on paraffin-embedded specimens. RESULTS: There were no significant
      differences in clinical stage, p53 and HER2 expression levels between the first
      and second primary tumors. The positive rates for ER and PR were 48% (25 of 52)
      and 46% (25 of 54) for the first tumors, but only 19% (10 of 52) and 32% (17 of
      54) for the second tumors (P = 0.004 for ER, P = 0.16 for PR), showing a
      significant loss of ER. CONCLUSIONS: Our findings indicate that p53 and HER2
      expression levels in the second tumors might be the same as those of the first
      tumors in metachronous bilateral breast carcinoma; however, loss of ER was more
      frequently observed in the second primary tumors than in the first tumors.

PMID- 11344481
TI  - Early complications following total gastrectomy for gastric cancer.
AB  - BACKGROUND: The study shows operative results with complications occurring in
      first 30 days after total gastrectomy for stomach cancer. METHODS: A
      retrospective analysis was performed using medical documentation and histological
      findings for 76 patients after total gastrectomy was done between 1990 and 1997.
      Mortality and postoperative complications were analyzed. Complications were
      sorted as specific and nonspecific. All operations were performed either for
      intestinal gastric cancer located in proximal stomach or for diffuse stomach
      cancer. All anastomoses were hand sewn. RESULTS: There were 43 male and 33 female
      patients. Postoperative mortality was 14.4%. The most frequent complications were
      dehiscence of the oesophago-jejunal anastomosis in 15.8% of operated patients,
      postoperative temperature without apparent infection in 5.2%, thrombophlebitis in
      5.2%, pneumothorax in 3.9%, hepatic necrosis in one patient (1.3%), and
      perforation of jejunal loop with nasogastric tube in another (1.3%) ended
      fatally. The average postoperative intra-hospital treatment lasted 12.3 days.
      Dehiscence of the oesophago-enteric anastomosis, resulted in generalized
      peritonitis in 66.6%. Six patients succumbed as a consequence, while two survived
      with subphrenic and interenteric abscesses. Pneumothorax in combination with
      total gastrectomy was always fatal. CONCLUSIONS: Routine use of stapling surgery,
      subspecialization in surgery, and better early intensive care monitoring and
      treatment could reduce the mortality rate.

PMID- 11344483
TI  - Expression of neural cell adhesion molecules (polysialylated form of neural cell
      adhesion molecule and L1-cell adhesion molecule) on resected small cell lung
      cancer specimens: in relation to proliferation state.
AB  - BACKGROUND AND OBJECTIVES: Alteration of homotypic cell-cell adhesion has been
      suggested to play an important role in tumor progression. The present study
      examined the relationship between neural cell adhesion molecules and state of
      proliferation of small cell lung cancer (SCLC) cells. METHODS: Seventeen
      surgically resected specimens of SCLC were immunohistochemically examined, by
      using monoclonal antibodies against neural cell adhesion molecule (NCAM) and its
      polysialic acid side chains, and L1 cell adhesion molecule (L1-CAM). Ki-67
      labeling indices were also determined immunohistochemically. RESULTS: All
      patients were positive for L1-CAM. Fifteen patients (88.2%) were positive for
      NCAM. Among the fifteen patients, nine (60.0%) were positive for NCAM PSA side
      chain. The probability of survival of the NCAM without PSA side chain group was
      significantly higher than that of the NCAM with PSA side chain group (log-rank
      test; P = 0.500). CONCLUSIONS: The expression of NCAM with PSA side chains might
      be a prognostic factor and NCAM a marker for SCLC. L1-CAM may be synthesized
      independent of state of proliferation of individual tumor cell and may affect
      clinical feature of SCLC.

PMID- 11344482
TI  - Risks and benefits of splenectomy in myelofibrosis with myeloid metaplasia: a
      retrospective analysis of 26 cases.
AB  - BACKGROUND AND OBJECTIVES: To evaluate the outcomes of splenectomy in
      myelofibrosis and myeloid metaplasia (MMM). METHODS: We retrospectively reviewed
      our records of 26 patients with MMM who underwent an open splenectomy at Boston
      University Medical Center between 1979 and 1995. Fourteen patients had agnogenic
      myeloid metaplasia (AMM) and 12 had myelofibrosis with antecedent
      myeloproliferative disorders (MF). The main indications for splenectomy were
      progressive transfusion-dependent anemia, painful splenomegaly, and
      hypercatabolic symptoms associated with cytopenia. RESULTS: Median time to
      splenectomy after the diagnosis of MMM was 29 months ranging from 1 to 96 months.
      Three patients (11%) died within 1 month after the surgery because of sepsis. The
      most common peri- and postoperative complications were pneumonia and other
      bacterial infections (42%), cardiac events (19%), acute bleeding (15%), ileus
      (15%), and venous thrombosis (12%). Of the eight surviving patients who underwent
      splenectomy for transfusion dependent anemia, six (75%) had improvement in their
      hematocrit levels with abolishment of blood transfusions. A durable symptomatic
      palliation was achieved in all patients. Liver enlargement was noted in seven
      patients at 1-year evaluation. None of these patients developed hepatic failure.
      Leukemic transformation occurred in 8 of 18 patients (44%) postsplenectomy. The
      median overall survival for the entire group was 58.5 and 28 months from the
      diagnosis of MMM and the time of splenectomy, respectively. There was no
      difference in survival rates between patients with AMM and MF. CONCLUSIONS:
      Splenectomy is an effective palliative procedure with an acceptable morbidity in
      selected patients with MMM. Progressive transfusion-dependent anemia should also
      be considered an indication for splenectomy in the absence of leukemic evolution.

PMID- 11344484
TI  - Expression of vascular endothelial growth factor in renal cell carcinoma and the
      relation to angiogenesis and p53 protein expression.
AB  - BACKGROUND AND OBJECTIVES: Vascular endothelial growth factor (VEGF) seems to
      play an important role in tumor angiogenesis. The tumor-suppressor gene p53 has
      been thought to regulate VEGF expression. We investigated the effect of VEGF
      expression on renal cell carcinoma (RCC) and the correlation between the
      expression of VEGF and tumor angiogenesis and p53 protein expression. METHODS:
      Sixty-two RCCs were examined by immunohistochemical studies with anti-VEGF, anti
      p53, and anti-CD34 antibodies. RESULTS: Forty tumors (80.6%) were classified as
      VEGF positive, and 28 tumors (45.2%) were positive for p53 protein. The
      microvessel density was 75.3 +/- 33.5. A significant correlation was found
      between VEGF expression and both the nuclear grade (P < 0.05) and the TNM stage
      (P < 0.05). The tumors with VEGF expression had a significantly higher
      microvessel density than those without VEGF expression (P < 0.01). There was no
      statistically significant correlation between p53 protein and VEGF expression. No
      statistically significant differences in survival were found to be associated
      with microvessel density, VEGF expression or p53 protein expression. By using
      multivariate survival analyses, nuclear grade (P < 0.05) and TNM stage (P < 0.05)
      were the only independent prognostic factors. CONCLUSIONS: Our data do not show a
      direct regulation of VEGF expression by p53. We suggest that VEGF expression
      plays a role in the promotion of angiogenesis in RCC.

PMID- 11344485
TI  - Mucinous adenocarcinoma arising in a neovagina using the sigmoid colon thirty
      years after operation: a case report.
AB  - BACKGROUND: Because of a relative rarity of the cases with an artificial vagina,
      the incidence of a case with malignant disease arising in the neovagina is
      extremely rare. A case of adenocarcinoma arising from a neovagina is presented
      with a review of the literature. CASE: A neovagina was constructed using the
      sigmoid colon at the age of 23 for congenital agenesis of the vagina, Rokitansky
      Kuster-Hauser syndrome. Subsequently, the patient had regular sexual intercourse
      for about 20 years. At the age of 53, she came to our outpatient clinic with a
      complaint of vaginal bleeding, and adenocarcinoma was found at the anterior wall
      of the neovagina adjoining the introitus. Total resection of the neovagina and
      adjuvant radiotherapy was performed. The pathological diagnosis was mucinous
      adenocarcinoma. CONCLUSIONS: In view of relatively low incidence of mucinous
      carcinoma arising in the sigmoid colon along with the ectopic localization, this
      case may have implications for the understanding of pathogenesis of sigmoid colon
      cancer.

PMID- 11344486
TI  - Pelvic neoplasms in children.
AB  - The pelvis of the infant and child has different anatomic relationships than the
      adolescent or adult pelvis, and the knowledge of congenital anomalies of the
      rectum and bladder can assist in treating the primary neoplasms of the pelvis.
      The most common neoplasms are rhabdomyosarcomas of the bladder, prostate, and
      vagina; sacrococcygeal teratoma; and the germ cell tumors, including teratomas,
      endodermal sinus tumors, and the choriocarcinomas. Rapidly improving chemotherapy
      for all of these lesions has resulted in a changed role for the surgeon. Less
      radical resection of these tumors is being performed whereas it is necessary to
      have more precise histologic and genetic identification of the tumor and the
      specific anatomic location and extent of the tumor in the pelvis. Survival for
      all types of childhood pelvic neoplasms has improved dramatically under the
      influence of the combined children's cancer study groups, which have been
      functioning for the last 20 years. Because of the complexities of diagnosis and
      treatment of these pelvic neoplasms in childhood and because the survival rates
      have dramatically improved with the most current therapy, these children should
      be cared for in a children's center that is part of the major children's cancer
      study groups.

PMID- 11344487
TI  - Internal mammary sentinel lymph node-technique of identification.

PMID- 11344489
TI  - Echocardiographic evaluation of patients cured of childhood cancer: a single
      center study of 117 subjects who received anthracyclines.
AB  - BACKGROUND: The risk of cardiomyopathy following exposure to anthracycline in
      asymptomatic long-term survivors of childhood cancer is still hard to predict and
      precisely quantify. To identify the impact of different cumulative doses, even
      within a non-high dose range, and the echocardiographic parameters suitable for
      evaluating cardiac function, we studied diastolic and systolic echocardiographic
      parameters in a cohort of patients followed in a single center. PROCEDURE: A
      total of 117 subjects were studied at a median time of 7 years after treatment
      completion. A complete M-mode, two-dimensional and Doppler echocardiographic
      study was obtained at rest in all patients according to the standard
      recommendations of the American Society of Echocardiography. RESULTS: Ninety-nine
      patients (85%) had completely normal cardiac function, while 18 had abnormal
      echocardiographic findings: 12 had one abnormal value, 5 had two, and 1 had three
      abnormal values. All the changes were in left ventricular dimensions, wall
      thickness or indices of systolic function; no alterations in left ventricular
      diastolic function parameters were found. None of the echocardiographic
      parameters correlated significantly with the cumulative dose of anthracyclines
      administered either at univariate analysis or after adjusting for sex, body
      surface area or considered risk factors. CONCLUSIONS: Subjects exposed to a
      median cumulative dose of 214 mg/m(2) had no echographic abnormalities a median
      of 7 years later. We did not find any correlation between cumulative
      anthracycline dose and the echocardiographic parameters tested. We now offer
      echocardiographic follow-up to patients with mildly reduced fractional shortening
      and/or ejection fraction to rule out late onset dysfunction.

PMID- 11344490
TI  - Concentration of vascular endothelial growth factor (VEGF) in the serum of
      patients with malignant bone tumors.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) is recognized as an
      important stimulator of angiogenesis. Formation of new blood vessels by
      angiogenic factors occurs in many biological processes, both physiological and
      pathological, among others in growth of primary solid malignant tumors and
      metastasis. This implies that the inhibition of angiogenic factors like VEGF
      would result in a suppression of tumor growth and metastasis formation. The aim
      of the present study was to compare preoperative serum VEGF levels of patients
      having malignant bone tumors with healthy controls to identify serum VEGF levels
      as a tumor marker. PROCEDURE: Blood sera from patients with high-grade
      osteosarcoma (n = 17), chondrosarcoma (n = 4) and Ewing sarcoma (n = 6) were
      taken at the time of diagnosis before biopsy and compared with sera from 129
      healthy persons. To measure VEGF levels in serum, a commercially available ELISA
      was used (Quantikine Human VEGF Immunoassay; R&D Systems). RESULTS: The observed
      geometric mean VEGF levels and 95% confidence intervals are 232.0 pg ml(-1)
      (168.9-318.5) for patients with high-grade osteosarcoma, 325.5 pg ml(-1) (169.3
      625.8) for patients with chondrosarcoma, 484.3 pg ml(-1) (284.0-826.0) for
      patients with Ewing sarcoma, as compared to 216.2 pg ml(-1) (192.8-242.5) for
      healthy individuals. CONCLUSIONS: While the sample means for the three groups of
      sarcoma patients were higher than the respective mean for the healthy controls,
      only the mean for the group with Ewing sarcoma is statistically significantly
      higher than the mean for the healthy controls. Despite the significant
      difference, VEGF levels are not suitable as a marker for Ewing sarcoma.

PMID- 11344491
TI  - Circulating concentrations of IGF-I and IGFBP-3 are not predictive of incidence
      or clinical behavior of pediatric osteosarcoma.
AB  - BACKGROUND: Preclinical studies suggest a role of insulin-like growth factor-1
      (IGF-1) in the proliferation of osteosarcoma cells in vivo. The purpose of this
      study is to address the relationship between serum levels of IGF-1 and its
      binding protein (IGFBP-3), and the clinical behavior and outcome of osteosarcoma
      in children, and to compare those levels present in osteosarcoma patients with a
      normal population. PROCEDURE: Serum IGF-1 and IGFBP-3 levels were determined by
      ELISA in 37 patients with osteosarcoma treated on the same treatment regimen (OS
      91 protocol), and who had available serum samples from diagnosis. IGF-1 and IGFBP
      3 levels were compared with those previously established in the normal
      population, matched for age and gender, and were correlated with the presence of
      metastatic disease, histologic response to preoperative chemotherapy, and event
      free survival. RESULTS: In osteosarcoma patients the median IGF-1 level was 275
      ng/ml (range, 105-613) and the median IGFBP-3 level was 3.4 mg/L (range, 2.3
      5.1). IGF-1 levels differed from those in the normal population (P = 0.029);
      although we anticipated higher IGF-1 levels than normal children, 68% of observed
      standardized scores were less than 0. Furthermore, IGF-1 or IGFBP-3 levels failed
      to correlate with the presence of metastatic disease (P = 0.12 and P = 0.12,
      respectively), histologic response (Rosen-Huvos grades 3/4 vs. grades 1/2) (P =
      0.95 and P = 0.71, respectively), or event-free survival (P = 0.52 and P = 0.41,
      respectively). There was a strong association observed between IGF-1 and IGFBP-3
      levels (P < 0.001). CONCLUSIONS: In this retrospective study of 37 patients, we
      found that circulating levels of IGF-1 and IGFBP-3 are not predictive of the
      development or clinical characteristics of pediatric osteosarcoma. However,
      further studies on a larger patient population should be performed in order to
      investigate this relationship.

PMID- 11344492
TI  - Opsoclonus-myoclonus-ataxia syndrome in neuroblastoma: clinical outcome and
      antineuronal antibodies-a report from the Children's Cancer Group Study.
AB  - BACKGROUND: Opsoclonus-myoclonus-ataxia (OMA) is a paraneoplastic neurologic
      syndrome affecting 2-3% of children with neuroblastoma. Although children with
      OMA and neuroblastoma may have higher survival, many experience a significant
      amount of late neurologic impairment, which may be immunologically mediated. The
      aim of this study was to compare the outcome of neuroblastoma patients with and
      without OMA, relating to prognostic factors, treatment, and the presence or
      absence of anti-neuronal antibodies. PROCEDURE: Questionnaires were mailed out
      requesting information on the current neurologic status of patients who submitted
      sera at diagnosis to the Children's Cancer Group serum bank from 1980 to 1994.
      Information was requested on clinical and biological patient characteristics as
      well as clinical aspects of the patients identified as having OMA syndrome,
      including presentation and treatment for OMA, late sequelae of OMA, the presence
      or absence of antineuronal antibodies, and survival. Sera from 16 of the OMA
      patients and 48 case-controls with neuroblastoma were assayed for anti-neuronal
      antibodies. RESULTS: Of the 675 responses received, 21 patients had OMA. Ninety
      percent of OMA patients presented with non-metastatic disease, vs. 35% of non-OMA
      patients. Estimated 3-year survival for the OMA patients with nonmetastatic
      disease (stage I, II, III) greater than 1 year of age was 100% vs. 77% for
      similar non-OMA patients (P = 0.0222). At follow-up, 14/19 evaluable OMA patients
      displayed some form of developmental or neurologic abnormality. There was no
      significant correlation of late sequelae with antineuronal antibodies, age, time
      between OMA symptoms and diagnosis, or treatment given for tumor or OMA. There
      was a significant correlation of late sequelae with lower stage disease (I and
      II) compared to more advanced disease (III and IV). CONCLUSIONS: Patients with
      OMA and neuroblastoma have excellent survival but a high risk of neurologic
      sequelae. Favorable disease stage correlates with a higher risk for development
      of neurologic sequelae. The role of anti-neuronal antibodies in late sequelae of
      OMA needs further clarification.

PMID- 11344493
TI  - Opsoclonus-myoclonus-ataxia syndrome in neuroblastoma: histopathologic features-a
      report from the Children's Cancer Group.
AB  - BACKGROUND: Opsoclonus-myoclonus-ataxia (OMA) is a paraneoplastic syndrome that
      occurs in about 2-3% of all cases of neuroblastoma. The histopathologic
      characteristics of neuroblastoma tumors associated with this syndrome were
      evaluated in a series of cases and controls. PROCEDURE: Pathology slides from a
      total of 54 neuroblastoma tumors were reviewed blindly. They included 13 tumors
      associated with opsoclonus-myoclonus and 41 age- and stage-matched controls. All
      tumors were classified into either the favorable (FH) or unfavorable histology
      (UH) group according to the International Neuroblastoma Pathology Classification
      (the Shimada system). Grade of lymphocytic infiltration was evaluated and
      presence or absence of lymphoid follicles was recorded in the individual tumor
      tissues. RESULTS: Twelve of 13 cases with opsoclonus-myoclonus were in the FH
      group. Twelve of 13 cases had diffuse (found in every section prepared from the
      multiple portions of the primary tumor) and extensive (occupying more than 50% of
      a single of multiple microscopic fields with x 100 magnification) lymphocytic
      infiltration with lymphoid follicles. Of the 41 control cases (27 FH and 14 UH
      tumors), 18 had focal areas of lymphocytic infiltration and six showed lymphoid
      follicles, but none had diffuse or extensive infiltration in their primary
      tumors. CONCLUSIONS: Diffuse and extensive lymphocytic infiltration with lymphoid
      follicles is a characteristic histologic feature of neuroblastic tumors with
      opsoclonus-myoclonus. This observation suggests an immune-mediated mechanism for
      this rare paraneoplastic syndrome.

PMID- 11344494
TI  - Absence of activating mutations in ras and gsp oncogenes in a cohort of nine
      patients with sporadic pediatric thyroid tumors.
AB  - BACKGROUND: Characterization of the genetic background of pediatric thyroid
      carcinomas could aid in distinguishing between differently staged tumors with
      respect to treatment and prognosis. Two known genetic factors associated with
      thyroid carcinoma, the proto-oncogenes gsp and ras were investigated. PROCEDURE:
      DNA was extracted from paraffin sections from both tumor and normal thyroid
      tissue of nine patients (ages 9-16 years). Of these patients, eight were
      diagnosed with papillary carcinoma and one with follicular adenoma. The coding
      exons of gsp and the three known ras genes (H, K, and N-ras) were screened for
      mutations using SSCP-analysis. RESULTS: There were no mutations present in the
      ras and gsp proto-oncogenes hot spots, however, LOH of H-ras (chromosome location
      11p15.5) was found in tumor tissue from one patient and a homozygous mutation in
      exon 12 of gsp causing a Pro-->Ser conversion was present in the thyroid tumor
      tissue from another patient. Two silent polymorphisms were detected, H-ras exon1,
      86T-->C and gsp exon 5, 81T-->C. CONCLUSIONS: Our results indicate that the
      ras/gsp mutations found are probably late events in the tumorigenesis
      representing general oncogenic stress. In conclusion, it seems that ras/gsp
      activation is not a factor in the mechanism causing sporadic thyroid carcinoma in
      children.

PMID- 11344496
TI  - Bisphosphonates as antialveolar macrophage therapy in pulmonary langerhans cell
      histiocytosis?

PMID- 11344495
TI  - Pharmacokinetic longitudinal studies of antibiotics administered via a permanent
      intraosseous device in micropigs.
AB  - BACKGROUND: In critically ill children, intraosseous (IO) administration of a
      medicine provides an alternate vascular access route when IV access is not
      readily available. We investigated the short and long-term efficacy and safety of
      a totally intraosseously implantable device. PROCEDURE: This study was undertaken
      in micropigs (i) to compare serum levels achieved by equal bolus dosages of two
      antibiotics (amikacin and vancomycin) administered through an intratibial needle,
      an intraosseous implantable device and central IV routes to determine whether
      standard parenteral dosing guidelines for antibiotics may be applied without
      modification for IO injection, and (ii) to show the efficiency of the implantable
      device over a prolonged period, as a permanent access to intraosseous space.
      RESULTS: The area under the plasma concentration time curves were similar for IV,
      intratibial and through the intraosseous implantable device, for intermittent
      administrations of amikacin and vancomycin, over a period of 6 months. However,
      vancomycin did not reach therapeutic levels via both IO routes. We did not find
      any alteration of amikacin and vancomycin pharmacokinetics over a period of 6
      months using the implantable device. No complication occurred. CONCLUSIONS: Long
      term administration of antibiotics through a totally implantable intraosseous
      device is feasible and safe in micropigs. Although the procedure seems promising,
      additional studies of the continuous infusion of chemotherapeutic agents, blood
      products and antimicrobial solutions are needed prior to use in humans.

PMID- 11344497
TI  - Atypical teratoid/rhabdoid tumor or medulloblastoma?

PMID- 11344498
TI  - Who can decide what is in a child's best interest? A problem-solving approach.

PMID- 11344499
TI  - Wilms tumour with unfavourable histology: implications for clinicians in the
      Third World.

PMID- 11344500
TI  - Unusual cause of extradural haemorrhage.

PMID- 11344501
TI  - Expansion of hematogones in a patient with Gaucher disease.

PMID- 11344502
TI  - Erythrocytosis in a child with a hepatic adenoma.

PMID- 11344503
TI  - Reversal of neurologic disturbances related to high-dose methotrexate by
      aminophylline.

PMID- 11344504
TI  - Fibrous pseudotumour of the tunica vaginalis testis.

PMID- 11344505
TI  - Local dissemination of hepatocellular carcinoma in a child after fine-needle
      aspiration.

PMID- 11344506
TI  - Management of obstructive jaundice caused by non-hodgkin lymphoma in children.

PMID- 11344507
TI  - Musculoskeletal manifestations of neuroblastoma at diagnosis.

PMID- 11344508
TI  - Laser-tissue soldering with biodegradable polymer films in vitro: film surface
      morphology and hydration effects.
AB  - BACKGROUND AND OBJECTIVE: Previous research introduced the concept of using
      biodegradable polymer film reinforcement of a liquid albumin solder for
      improvement of the tensile strength of repaired incisions in vitro. In this
      study, the effect of creating small pores in the PLGA films on the weld breaking
      strength is studied. Additionally, the effect of hydration on the strength of the
      reinforced welds is investigated. STUDY DESIGN/MATERIALS AND METHODS: A 50%(w/v)
      bovine serum albumin solder with 0.5 mg/mL Indocyanine Green dye was used to
      repair an incision in bovine aorta. The solder was coagulated with an 806-nm CW
      diode laser. A poly(DL-lactic-co-glycolic acid) (PLGA) film was used to reinforce
      the solder (the controls had solder but no reinforcement). Breaking strengths
      were measured acutely and after hydration in saline for 1 and 2 days. The data
      were analyzed by ANOVA (P < 0.05) and multiple comparisons of means were
      performed using the Newman-Keuls test. RESULTS: The creation of pores in the PLGA
      films qualitatively improved the film flexibility without having an apparent
      adverse effect on the breaking strength, while the actual technique of applying
      the film and solder had more of an effect. The acute maximum average breaking
      strengths of some of the film reinforced specimens (114.7 g-134.4 g) were
      significantly higher (P < 0.05) than the acute maximum average breaking strength
      of the unreinforced control specimens (68.3 g). Film reinforced specimens were
      shown to have a statistically significantly higher breaking strength than
      unreinforced controls after 1- and 2-day hydration. CONCLUSIONS: Reinforcement of
      liquid albumin solders in laser-assisted incision repair appears to have
      advantages over conventional methods that do not reinforce the cohesive strength
      of the solder in terms of acute breaking strength and after immersion in moist
      environments for short periods of time. Using a film with the solder applied to
      one surface only may be advantageous over other techniques.

PMID- 11344509
TI  - Continuous changes in the optical properties of liver tissue during laser-induced
      interstitial thermotherapy.
AB  - BACKGROUND AND OBJECTIVE: Laser-induced thermotherapy (LITT) is a promising
      treatment for irresectable liver tumors. To predict the effects of laser
      applications and to optimize treatment planning in LITT, it is essential to gain
      knowledge about light distribution in tissue, tissue optical properties
      (absorption, scattering, anisotropy, penetration depth), and their continuous
      changes during therapy. STUDY DESIGN/MATERIALS AND METHODS: Measurements of
      optical properties were performed with a double integrating-sphere system and a
      laser diode (830 nm). Porcine liver tissue samples were examined in a native
      state (35 degrees C) and after exposure to different temperatures (45 degrees C
      to 80 degrees C). RESULTS: Rising temperature was accompanied by a decrease in
      the absorption coefficient and anisotropy factor and an increase in the
      scattering coefficient. These changes were only significant in the temperature
      range of 50 degrees to 65 degrees C (P < 0.01). The optical penetration depth
      decreased from 3.1mm in the native state to 1.7mm at 65 degrees C (P < 0.01).
      Above 65 degrees, there was no significant change in the tissue optical
      properties. CONCLUSIONS: The optical properties of liver tissue change
      significantly under the influence of tissue heating, resulting in a decreased
      optical penetration depth. These changes occur mainly in the temperature range of
      50 degrees C to 65 degrees C, corresponding to protein denaturation. To ensure a
      safe and effective procedure, an adjustment of the laser power to the actual
      penetration depth is recommended during therapy.

PMID- 11344510
TI  - Optical-thermal simulation of tonsillar tissue irradiation.
AB  - BACKGROUND AND OBJECTIVE: Despite laser applications targetted toward tonsillar
      tissue, there has been no characterization of underlying optical and thermal
      events during laser irradiation of tonsillar tissue. STUDY DESIGN/MATERIALS AND
      METHODS: The optical properties of canine and human tonsils were determined at
      805 nm (diode laser) and 1,064 nm (Nd:YAG laser). An optical-thermal simulation
      was developed to predict the temperature rise in irradiated human tonsils.
      RESULTS: The optical properties of human and canine tonsillar tissue are similar
      at both wavelengths. The optical-thermal simulation was validated and predicts
      that at 10 W and 1 minute of irradiation, the heat will be contained within the
      human tonsil. The diode laser causes more superficial heating than the Nd:YAG
      laser. CONCLUSIONS: The safety of irradiating human tonsils was shown. The diode
      laser is superior to the Nd:YAG laser because less heat affects collateral
      structures. The optical-thermal simulation detailed in this study can be used to
      predict the temperature rise in tissues undergoing irradiation.

PMID- 11344511
TI  - Alternative indications for laser-assisted tympanic membrane fenestration.
AB  - BACKGROUND AND OBJECTIVE: To assess the utility of the CO(2) Flashscanner laser
      for treatment of selected middle ear diseases other than otitis media with
      effusion (OME) and acute otitis media (AOM). STUDY DESIGN/MATERIALS AND METHODS:
      A retrospective review of the records of 144 patients treated with the
      OtoLAM((R)) device, a Flashscanner laser, between July 1, 1998, and February 29,
      2000. Patients treated for AOM or OME were excluded. RESULTS: Data are presented
      on 11 patients (17 ears). Four indications were identified: Elimination of middle
      ear fluid before auditory brainstem response with or without otoacoustic emission
      testing (ABR +/- OAE), barotrauma, eustachian tube obstruction, tympanocentesis
      when a culture of middle ear fluid was deemed necessary. All tympanic membranes
      (TM) healed. CONCLUSIONS: Fenestration of the TM can be accomplished for both
      diagnostic and therapeutic purposes. Laser assisted tympanic membrane
      fenestration seems to be effective in the management of middle ear fluid before
      ABR +/- OAE, barotrauma, eustachian tube dysfunction, and for tympanocentesis.

PMID- 11344512
TI  - Contact laser-assisted neuroendoscopy can be performed safely by using pretreated
      'black' fibre tips: experimental data.
AB  - BACKGROUND AND OBJECTIVE: Laser-assisted endoscopic neurosurgery by using
      conventional fibres requires the use of high-power laser light. Because this is
      potentially hazardous, we developed a pretreated fibre tip and evaluated tissue
      effects in vitro and in vivo. STUDY DESIGN/MATERIALS AND METHODS: By applying a
      highly absorbing coating to the front of the ball tip, almost all laser light is
      transformed into thermal energy, instantly producing ablative temperatures at the
      tip itself. The temperature distribution was examined by using an in vitro
      thermal imaging technique. The in vivo effect on rabbit cerebral tissue was
      examined macroscopically and histologically. RESULTS: By using a conventional
      fibre tip, ablation was not observed, despite the use of high energy and power
      (20 W for 10 seconds), whereas histology and thermal imaging demonstrated
      deleterious effects deeply into the cerebral tissue. By using the coated fibre
      tip, ablation was observed at low energy and power (1 W for 1 second) with
      thermal effects restricted to superficial structures. CONCLUSIONS: We show that
      laser-assisted neuroendoscopy can only be considered to be safe when pretreated
      "black" fibre tips are used, as laser light damages deep structures.

PMID- 11344513
TI  - Urine analysis by laser Raman spectroscopy.
AB  - BACKGROUND AND OBJECTIVE: We examine the use of Raman spectroscopy to analyze
      components in human urine. STUDY DESIGN/MATERIALS AND METHODS: Targeted urine
      components include urea, uric acid, and creatinine. RESULTS: Urea concentration
      in urine is sufficiently high that normal Raman spectroscopy may be used for its
      analysis. All other components are in low concentrations requiring the use of
      surface-enhanced Raman spectroscopic methods (SERS). CONCLUSIONS: Both normal
      Raman and SERS approaches have been investigated for total urine-nitrogen
      determination, urine urea-nitrogen determination, and for the urea/creatinine
      excretion ratio.

PMID- 11344514
TI  - Comparison of Er:YAG and 9.6-microm TE CO(2) lasers for ablation of skull tissue.
AB  - BACKGROUND AND OBJECTIVE: Craniotomy by using a drill and saw frequently results
      in fragmentation of the skull plate. Lasers have the potential to remove the
      skull plate intact, simplifying the reconstructive surgery. STUDY
      DESIGN/MATERIALS AND METHODS: Transverse-excited CO(2) lasers operating at the
      peak absorption wavelength of bone (lambda = 9.6 microm) and with pulse durations
      of 5-8 microsec, approximately the thermal relaxation time in hard tissue,
      produced high ablation rates and minimal peripheral thermal damage. Both thick (2
      mm) and thin (250 microm) bovine skull samples were perforated and the ablation
      rates calculated. Results were compared with Q-switched and free-running Er:YAG
      lasers (lambda = 2.94 microm, tau(p) = 0.5 microsec and 300 microsec). RESULTS:
      The CO(2) laser produced ablation rates of up to 60 and 15 microm per pulse for
      thin and thick sections, respectively, and perforated thin and thick sections
      with fluences of less than 1 J/cm(2) and 6 J/cm(2), respectively. There was no
      discernible thermal damage and no need for water irrigation during ablation.
      Pulse durations > or =20 microsec resulted in significant tissue charring, which
      increased with the pulse duration. Although the free-running Er:YAG laser
      produced ablation rates of up to 100 microm per pulse, fluences of 10 J/cm(2) and
      30 J/cm(2) were required to perforate thin and thick samples, respectively, and
      peripheral thermal damage measured 25-40 microm. CONCLUSIONS: In summary, the
      novel 5- to 8-microsec pulse length of the TE CO(2) laser is long enough to avoid
      a marked reduction in the ablation rate due to plasma formation and short enough
      to avoid peripheral thermal damage through thermal diffusion during the laser
      pulse. Furthermore, in vivo animal studies with the TE CO(2) laser are warranted
      for potential clinical application in craniotomy and craniofacial procedures.

PMID- 11344515
TI  - Photomechanical transdermal delivery: the effect of laser confinement.
AB  - BACKGROUND AND OBJECTIVE: Photomechanical waves can transiently permeabilize the
      stratum corneum and facilitate the delivery of drugs into the epidermis and
      dermis. The present study was undertaken to assess the effect of pulse
      characteristics to the penetration depth of macromolecules delivered into the
      skin. STUDY DESIGN/MATERIALS AND METHODS: Photomechanical waves were generated by
      confined ablation with a Q-switched ruby laser. Fluorescence microscopy of frozen
      biopsies was used to assay the delivery of macromolecules through the stratum
      corneum and determine the depth of penetration. RESULTS: Photomechanical waves
      generated by confined ablation of the target have a longer rise time and duration
      than those generated by direct ablation. Confined ablation required a lower
      radiant exposure (from approximately 7 J/cm(2) to approximately 5 J/cm(2)) for an
      increase in the depth of delivery (from approximately 50 microm to approximately
      400 microm). CONCLUSIONS: Control of the characteristics of the photomechanical
      waves is important for transdermal delivery as they can affect the depth of drug
      penetration into the dermis.

PMID- 11344516
TI  - Analytical method to examine the effects of carbon dioxide lasers on skin: a
      study using wrinkles induced in hairless mice.
AB  - BACKGROUND AND OBJECTIVE: Investigation of the wrinkle smoothing process elicited
      by CO(2) laser treatment is important for understanding the mechanism involved in
      their repair. STUDY DESIGN/MATERIALS AND METHODS: Hairless mice with wrinkles
      induced in their dorsal skin by long-term exposure to ultraviolet radiation in
      the wavelength range of 290-320 nm were treated with a CO(2) laser. By using this
      model, we investigated the external appearance, histologic changes, and the
      mechanical properties of the skin during the wrinkle repair. RESULTS: Laser
      treatment with an appropriate intensity caused wrinkles to smooth completely. In
      the healing process, reepithelialization and collagen tissue regeneration in the
      upper dermis was observed. However, marked changes in the skin were noted, such
      as increases in the collagen layer and in the skin thickness, and changes in the
      mechanical properties of the skin, despite the favorable external appearance.
      CONCLUSIONS: An abnormal state characterized by excessive collagen regeneration
      and other changes in the dermis occur concomitantly with wrinkle smoothing.

PMID- 11344517
TI  - Low-power helium: neon laser irradiation enhances production of vascular
      endothelial growth factor and promotes growth of endothelial cells in vitro.
AB  - BACKGROUND AND OBJECTIVE: Numerous reports suggest that low-power laser
      irradiation (LPLI) is capable of affecting cellular processes in the absence of
      significant thermal effect. The objective of the present study was to determine
      the effect of LPLI on secretion of vascular endothelial growth factor (VEGF) and
      proliferation of human endothelial cells (EC) in vitro. STUDY DESIGN/MATERIALS
      AND METHODS: Cell cultures were irradiated with single different doses of LPLI
      (Laser irradiance from 0.10 to 6.3 J/cm(2)) by using a He:Ne continuous wave
      laser (632 nm). VEGF secretion by smooth muscle cells (SMC) and fibroblasts was
      quantified by sandwich enzyme immunoassay technique. The endothelial cell
      proliferation was measured by Alamar Blue assay. VEGF and transforming growth
      factor beta (TGF-beta) expression by cardiomyocytes was studied by reverse
      transcription-polymerase chain reaction (RT-PCR). RESULTS: We observed that (1)
      LPLI of vascular and cardiac cells results in a statistically significant
      increase of VEGF secretion in culture (1.6-fold for SMC and fibroblasts and 7
      fold for cardiomyocytes) and is dose dependent (maximal effect was observed with
      LPLI irradiance of 0.5 J/cm(2) for SMC, 2.1 J/cm(2) for fibroblasts and 1.05
      J/cm(2) for cardiomyocytes). (2) Significant stimulation of endothelial cell
      growth was obtained with LPLI-treated conditioned medium of SMC (maximal increase
      was observed with LPLI conditioned medium with irradiance of 1.05 J/cm(2) for SMC
      and 2.1 J/cm(2) for fibroblasts. CONCLUSIONS: Our studies demonstrate that low
      power laser irradiation increases production of VEGF by SMC, fibroblasts, and
      cardiac myocytes and stimulates EC growth in culture. These data may have
      significant importance leading to the establishment of new methods for
      endoluminal postangioplasty vascular repair and myocardial photoangiogenesis.

PMID- 11344518
TI  - Adhesion of composite resins to enamel irradiated by the Er:YAG laser:
      application of the ultrasonic scaler on irradiated surface.
AB  - BACKGROUND AND OBJECTIVE: The clinical use of the Er:YAG laser in cavity
      preparation has become widespread. With respect to cavities prepared with the
      Er:YAG laser, restorations using composite resins and glass ionomer cements are
      common. The bond strength of current resin bonding systems to ground enamel is 14
      30 MPa, whereas the strength to Er:YAG laser-irradiated enamel, regardless of the
      use or non-use of phosphoric acid etching is less than 10 MPa. STUDY
      DESIGN/MATERIALS AND METHODS: In this investigation, an ultrasonic scaler was
      tested as a technique to increase the bond strength of composite resins to the
      Er:YAG irradiated enamel surface. RESULTS: The application of the ultrasonic
      scaler significantly increased bond strength. CONCLUSIONS: The tensile bond
      strength in the groups treated with the ultrasonic scaler exhibited approximately
      twice the strength observed in groups treated with laser irradiation alone.

PMID- 11344519
TI  - Microleakage of composite fillings in Er,Cr:YSGG laser-prepared class II
      cavities.
AB  - BACKGROUND AND OBJECTIVE: If there is insufficient bonding to the enamel, the
      shrinkage of composites that occurs during polymerization can result in a gap
      between the filling material and the cavity wall. This gap permits the passage of
      bacteria or their metabolic products and also of various molecules and ions. This
      leads to hypersensitivity or secondary caries and is thus one of the causes of
      the failures encountered in composite restorations. The aim of this study was to
      examine the quality of the margins of composite fillings in Er,Cr:YSGG laser
      prepared cavities by means of dye penetration. The results were compared with
      those of restoration in conventionally prepared and conditioned cavities. STUDY
      DESIGN/MATERIALS AND METHODS: To this end, 45 class II cavities in extracted
      molars were prepared. The teeth were divided into three groups. The first group
      served as a control group. The cavities were prepared in the classical manner by
      using a diamond, beveled and subsequently conditioned by the etching method. In
      group 2, the cavities were prepared and conditioned exclusively with the
      Er,Cr:YSGG laser. In group 3, laser preparation was supplemented by conditioning
      of the cavity with phosphoric acid. RESULTS: No significant difference could be
      found between the classical preparation technique in combination with etching and
      the laser preparation method with supplementary etching (group 3). The degree of
      dye penetration was highest in the group undergoing laser-prepared restoration
      without additional etching (group 2) (Wilcoxon test, P < 0.017). CONCLUSIONS:
      Although it was found in previous studies that there is no significant difference
      between bond strength of acid etched enamel and Er,Cr:YSGG laser etched enamel,
      the dye penetration rate differs. On the basis of the results of our study, the
      additional use of etching after Er,Cr:YSGG laser preparation is recommended as it
      is used in the classical cavity preparation technique.

PMID- 11344520
TI  - Production of narrow but deep lesions suitable for ablation of atrial
      fibrillation using a saline-cooled narrow beam Nd:YAG laser catheter.
AB  - BACKGROUND AND OBJECTIVE: Lines of radiofrequency ablation for cure of atrial
      fibrillation are broad, and the consequent loss of atrial mass may impair atrial
      function and contribute to the risk of stroke. We studied whether Nd:YAG laser
      could produce deep but narrower lesions. STUDY DESIGN/MATERIALS AND METHODS:
      Laser lesions were made in ventricular myocardium of nonperfused ovine hearts and
      at thoracotomy in dogs. RESULTS: Lesions were well demarcated, deep, and narrow.
      Saline irrigation prevented crater formation for energy levels below 200 J.
      Lesion depth increased with increasing duration of ablation (maximum 5.3 +/-
      0.8mm, P < 0.01). The depth to width ratio was >1 in all cases (maximum 2.5 +/-
      1.6). The narrowest lesions were made by using high power, short duration of
      exposure, and intermittent delivery. CONCLUSIONS: Irrigated Nd:YAG laser can be
      used to make deep narrow myocardial lesions without crater formation. Laser
      ablation may be more suitable than radiofrequency ablation for intraoperative or
      catheter-based cure of atrial fibrillation.

PMID- 11344521
TI  - Endovascular photodynamic therapy using mono-L-aspartyl-chlorin e6 to inhibit
      Intimal hyperplasia in balloon-injured rabbit arteries.
AB  - BACKGROUND AND OBJECTIVE: Intimal hyperplasia (IH) leading to restenosis is a
      major complication of arterial revascularization. The purpose of this study was
      to investigate the effect of photodynamic therapy (PDT) using mono-L-aspartyl
      chlorin e6 (NPe6) as a photosensitizer and intraluminal radial irradiation for
      inhibition of IH experimentally. STUDY DESIGN/MATERIALS AND METHODS: Study of
      laser transmission through the blood indicated that exclusion of blood is a
      prerequisite for intraluminal PDT. For homogeneous radial laser irradiation to
      the vessel wall, we used a newly developed cylindrical diffusing balloon laser
      fiber. Injuries were induced by pulling a balloon catheter through the right
      iliac artery of rabbits. One and 6 hours after the NPe6 injection (5mg/kg i.v.),
      drug distribution was examined by fluorescence microscopy. Nineteen rabbits
      received NPe6 at the time of injuries and PDT was performed with 664-nm laser at
      30 and 10 J/cm(2) (20, 30, 40 mW/cm(2)) 1 hour after the injuries. The arteries
      were harvested at 2 days. In a second group of rabbits, PDT was given at 30
      mW/cm(2) (30 J/cm(2)). Two weeks after treatment, the arteries were removed and
      examined histologically. RESULTS: NPe6 was found to be distributed selectively in
      the injured media. Endovascular NPe6-PDT showed complete depletion of smooth
      muscle cells even with 10 J/cm(2) at 2 days. IH was significantly inhibited at 14
      days after PDT. CONCLUSIONS: Endovascular PDT of injured artery using NPe6 can
      prevent IH in this model of arterial wall injury and may become clinically useful
      for the prophylaxis of IH.

PMID- 11344522
TI  - Commentary: advances in the laboratory diagnosis of celiac disease.
AB  - Anti-endomysial autoantibodies are very useful in the diagnosis and monitoring of
      celiac disease (gluten-sensitive enteropathy) due to their high sensitivity and
      specificity for that disorder. The recent discovery that the autoantigen
      responsible for the endomysial pattern is tissue transglutaminase (tTG) has led
      to the commercial development of automated enzyme immunoassays for quantitation
      of that autoantibody. These assays are standardized to provide highly accurate
      and comparable testing between laboratories for anti-tTG autoantibodies. Celiac
      disease is a common genetic disease in populations of Europe and the United
      States. It has a spectrum of expression ranging from silent or mild to severe,
      with resulting malabsorption that produces multiple-organ system effects due to
      malnutrition. Many cases miss the diagnosis because the symptoms are not classic
      or the clinical syndrome is not severe. Because the treatment of celiac disease
      (avoidance of wheat products) is so effective and inexpensive and because celiac
      disease is so common in selective populations, a highly reliable test for its
      detection such as anti-tTG should find wide application in clinical practice.

PMID- 11344523
TI  - IgA antibodies against endomysium and transglutaminase: a comparison of methods.
AB  - Recently, the endomysial antigen has been identified as the protein cross-linking
      enzyme known as tissue transglutaminase (tTG). Our objective was to compare a
      novel enzyme immunoassay (EIA) that detects IgA antibody against tTG to two
      standard IFA methods utilizing thin tissue sections of rat kidney/rat stomach
      (KS) and distal primate esophagus (PE) as substrates to detect IgA antibody
      against endomysium (EMA). Sera from 100 patients suspected of having gluten
      sensitive enteropathy (GSE) and 23 sera possessing various antibodies used for
      EIA cross-reactivity studies were included. Additional tests, performed routinely
      in our laboratory, were utilized to further assess sera from patients suspected
      having GSE. These tests include anti-gliadin IgA antibody (AGA) and anti
      reticulin IgA antibody (ARA) and are part of the European Society for Pediatric
      Gastroenterology and Nutrition (ESPGAN) revised criteria for diagnosing GSE. When
      compared to IFA using KS, the tTG EIA had a sensitivity of 87.5%, was 97.1%
      specific, and had an overall agreement of 94.0%. When compared to IFA using PE,
      the tTG EIA had a sensitivity of 92.6%, was 93.2% specific, and had an overall
      agreement of 93.0%. When the KS IFA was compared to the PE IFA for EMA, the KS
      IFA had a sensitivity of 96.3%, was 91.8% specific, and had an overall agreement
      of 93.0%. The majority of sera that were positive for tTG but were negative by
      IFA (KS, n = 2/PE, n = 5) possessed IgA antibodies against gliadin and/or
      reticulin. Five of six sera with negative results by PE IFA were positive by the
      KS IFA and possessed one or more antibodies to tTG and/or gliadin and/or
      reticulin. We conclude that the tTG EIA compares well to both KS and PE IFAs when
      detecting IgA antibody against endomysium. We do not recommend the use of PE to
      detect EMA primarily because of the inconsistencies (i.e., tissue selection,
      quality, and preparation) and limited availability of commercially prepared PE
      tissue.

PMID- 11344524
TI  - Role of anti-transglutaminase (anti-tTG), anti-gliadin, and anti-endomysium serum
      antibodies in diagnosing celiac disease: a comparison of four different
      commercial kits for anti-tTG determination.
AB  - The aims of this study were: (1) to compare the diagnostic efficacy for celiac
      disease (CD) diagnosis of serum determination of anti-gliadin (AG) (IgA and IgG)
      and anti-endomysium (AE) with that of anti-transglutaminase (AtTG); and (2) to
      compare the accuracy of four different assays to measure AtTG. We studied 72
      children: the histological diagnosis of CD was made in 38 cases and excluded in
      the remaining 34 children. In fasting sera we measured AE, AG-IgA and IgG, and
      AtTG, the latter with four different commercial kits (Eurospital, Medipan, Inova,
      Arnika). Moreover AtTG was measured in a group of 58 CD children after a gluten
      free diet. AE was positive in all but 1 case of CD patients (sensitivity = 97%);
      false positive results were found in 1/34 controls (specificity = 97%). When a
      specificity of 95% was fixed, the sensitivities were 97% for AE, 83% for AG-IgA,
      and 63% for AG-IgG; the sensitivities of anti-tTG were 90, 84, 84, and 75% when
      measured with Eurospital, Medipan, Inova, and Arnika kits respectively. The new
      AtTG seems to be accurate enough to be proposed as a noninvasive diagnostic tool
      for CD diagnosis; the 4 kits analyzed showed similar diagnostic efficacy.

PMID- 11344525
TI  - Deproteinization of serum: another best approach to eliminate all forms of
      bilirubin interference on serum creatinine by the kinetic Jaffe reaction.
AB  - The negative interference of conjugated, unconjugated, and delta bilirubin on
      patient serum creatinine determined by the kinetic Jaffe reaction is the
      unresolved problem. We compared bilirubin interference on thirty patients' serum
      creatinine obtained from four analyzers, with and without deprotenization before
      the Jaffe reaction, to the Vitros dry enzymatic method. We found significant
      negative interference from bilirubin on serum creatinine in all samples directly
      applied to four wet chemical methods, except the one incorporated with serum
      blank rate. The negative interferences linearly related to bilirubin
      concentration. However, bilirubin did not interfere on serum creatinine obtained
      from all wet chemical methods incorporated with deproteinization process before
      the reaction. We conclude that deproteinized serum before the reaction is the
      best approach to eliminate all forms of bilirubin interference on serum
      creatinine determined by the kinetic Jaffe reaction.

PMID- 11344526
TI  - Quantitative PCR determination of human cytomegalovirus in blood cells.
AB  - We evaluated a rapid and sensitive method to determine human cytomegalovirus
      (CMV) DNA levels in blood cells using a quantitative polymerase chain reaction
      (PCR) technique. This method is based on real-time detection of PCR using a dual
      fluorescence-labeled probe and a sequence detector. Ten copies of CMV DNA were
      detected, when 1 microg of DNA from blood samples was used with this method, and
      a good correlation was obtained between increased concentrations of copy numbers
      calculated and measured copy numbers of CMV DNA (r = 0.999). Forty normal
      subjects exhibited no copies of CMV DNA. On the other hand, a 6-month-old girl
      tested positive for increased levels 4 weeks after liver transplant. This method
      is simple, accurate, and sensitive for the quantitative detection of CMV DNA in
      vivo, indicating possible applications for the diagnosis and monitoring of CMV
      infection.

PMID- 11344527
TI  - Long-term benefit of genotypic-guided therapy and prevalence of multinucleoside
      resistance in an Italian group of antiretroviral multiexperienced patients.
AB  - Multiple nucleoside resistance involves specific genetic changes in the HIV-1
      reverse transcriptase gene, such as Q151M mutation and an insertion of two serine
      aminoacids at RT codon 69. Among 432 patients failing antiretroviral therapy,
      five (1.15%) harboured viruses with Q151M mutation into the RT gene and no
      viruses were identified harbouring insertion at codon 69. Also we have studied
      the long-term benefit of HIV genotypic testing with the failure to reach a viral
      load below 50 copies/ml within 1 year of antiretroviral therapy using as the
      primary end-point. A group of 64 HIV-positive antiretroviral multiexperienced
      patients were examined, all of them failing the current ART. HIV-RNA changed -0.8
      log at month 4 and +0.1 log and -0.5 log at months 8 and 12, respectively. The
      proportion of patients with viral load below 50 copies/ml was 19.3, 32.8, and
      28.1% at months 4, 8, and 12, respectively. In multidrug-experienced patients,
      genotype-guided therapy is not in fact able to achieve complete viral suppression
      in more than 30% of patients after 1 year of ART. The development of more precise
      resistance tests and interpretations are needed for better control of HIV
      replication. Other metabolic/pharmacokinetics factors of poor drug adherence
      should also be assessed.

PMID- 11344528
TI  - Real-time identification of Pseudomonas aeruginosa direct from clinical samples
      using a rapid extraction method and polymerase chain reaction (PCR).
AB  - Pseudomonas aeruginosa has emerged as one of the most problematic Gram-negative
      nosocomial pathogens. Bacteremia caused by P. aeruginosa is clinically
      indistinguishable from other Gram-negative infections although the mortality rate
      is higher. This microorganism is also inherently resistant to common antibiotics.
      Standard bacterial identification and susceptibility testing is normally a 48
      hour process and difficulty sometimes exists in rapidly and accurately
      identifying antimicrobial resistance. The Polymerase Chain Reaction (PCR) is a
      rapid and simple process for the amplification of target DNA sequences. However,
      many sample preparation methods are unsuitable for the clinical laboratory
      because they are not cost effective, take too long to perform, or do not provide
      a good template for PCR. Our goal was to provide same-day results to facilitate
      rapid diagnosis. In this report, we have utilized our rapid DNA extraction method
      to generate bacterial DNA direct from clinical samples for PCR. The lower
      detection level for P. aeruginosa was estimated to be 10 CFU/ml. In addition, we
      wanted to compare the results of a new rapid-cycle DNA thermocycler that uses
      continuous fluorescence monitoring with the results of standard thermocycling. We
      tested 40 clinical isolates of P. aeruginosa and 18 non-P. aeruginosa isolates
      received in a blinded fashion. Coded data revealed that there was 100%
      correlation in both the rapid-cycle DNA thermocycling and standard thermocycling
      when compared to standard clinical laboratory results. In addition, total results
      turn-around time was less than 1 hour. Specific identification of P. aeruginosa
      was determined using intragenic primer sets for bacterial 16S rRNA and
      Pseudomonas outer-membrane lipoprotein gene sequences. The total cost of our
      extraction method and PCR was $2.22 per sample. The accuracy and rapidness of
      this DNA-extraction method, with its PCR-based identification system, make it an
      ideal candidate for use in the clinical laboratory.

PMID- 11344529
TI  - Development of two ELISA for estrogen and progesterone receptor with sufficient
      sensitivity for fine needle aspirate and core biopsy.
AB  - The quantitative determination of estrogen and progesterone receptors (PR and ER)
      in breast tumor cytosol has been routinely performed in clinical laboratories to
      aid in the selection between hormonal and chemotherapy and also to predict
      prognosis. However, the small amount of tissue available from the increasingly
      popular fine-needle aspiration and core biopsies from breast cancer patients
      requires more sensitive immunoassays for receptor quantification. We have
      developed two sensitive immuno-assays for ER and PR on microplate with the use of
      recently available anti-ER and anti-PR antibodies of higher affinity and a
      powerful signal magnification agent, namely Amdex. The calibrator was a pooled
      breast tumor cytosol used as calibrator and calibrated against Abbott kits. The
      protein concentration of the cytosol and the upper normal cutoffs for our assays
      were reduced to approximately 0.2 mg/mL and 3 fmol/0.2 mg/mL, respectively. Both
      assays have sensitivities close to 1 fmol/mL, which are sufficiently sensitive
      for the receptor quantification in fine-needle aspiration biopsies and cord
      biopsies of breast tumor.

PMID- 11344530
TI  - Simultaneous determination of total plasma glutathione, homocysteine,
      cysteinylglycine, and methionine by high-performance liquid chromatography with
      electrochemical detection.
AB  - We here describe an ion-exchange high-performance liquid chromatography technique
      with electrochemical detection for rapid quantification of glutathione,
      homocysteine, cysteinylglycine, and methionine. The analytical validation of the
      technique showed within-assay and between-assay coefficients of variation between
      3.1 and 4.3%, and 3.7 and 8.6%, respectively. Percentages of recovery for
      overload and dilution tests were between 87 and 120%. Detection limits were 1
      micromol/L for methionine and 0.5 micromol/L for other compounds. There was no
      interference with any physiological and pharmacological substances possessing a
      thiol function. Aminothiol concentrations determined in 100 control subjects (50
      women and 50 men) showed no age- or sex-rated differences for except for
      homocysteine which was increased (+ 28%) in oldest subjects of both sexes. In 60
      patients at risk (30 with chronic renal failure, 30 with diabetes), homocysteine
      concentration was significantly increased. No variation in other aminothiols was
      observed in diabetic subjects. Methionine was decreased and cysteinylglycine was
      increased in patients with chronic renal failure. The present technique-rapid,
      easy to use, and reliable-appears suitable for routine application in the
      exploration of aminothiol metabolic pathways including mechanisms of
      hyperhomocysteinemia.

PMID- 11344531
TI  - Evaluation of urinary rapid test for Helicobacter pylori in general practice.
AB  - There is increasing interest in noninvasive tests for the diagnosis of
      Helicobacter pylori (H. pylori) infection. One such test, a urine-based rapid
      test kit (RAPIRUN H. pylori Antibody, Otsuka Pharmaceutical Co., Ltd.) for
      detection of antibody to H. pylori, has been developed and is considered ideal.
      In addition to its noninvasiveness and safe handling-due to use of urine as a
      sample-the assay procedure used for the urinary rapid test is very simple. Only
      10-20 minutes are required to complete an assay, and no instruments are needed.
      The aim of this study was to examine the clinical usefulness of this urine-based
      rapid test. A total of 189 patients, including 76 patients with gastroduodenal
      disease, were recruited. A pair of random single-void urine and serum samples was
      collected from each of the 189 patients, and antibody to H. pylori in the urine
      and serum samples was measured using the urine-based rapid test kit and three
      commercially available serum-based ELISA kits. For the patients with
      gastroduodenal disease, invasive diagnostic methods using endoscopic biopsy
      specimens such as culture, histology, and rapid urease test were also performed.
      The sensitivity, specificity, and accuracy of the urinary rapid test were
      evaluated on the basis of the three serum ELISA results or the invasive
      diagnostic results. In addition, various urinalyses were performed, and the
      effects of substances existing in urine on the urinary rapid test results were
      examined. Of the 189 patients, the urinary rapid test was positive for 110
      (58.2%), negative for 78 (41.3%), and invalid for only one patient (0.5%). Based
      on the three serum-based ELISA results, the sensitivity, specificity, and
      accuracy of the urinary rapid test were 93.7, 88.9, and 92.2%, respectively. On
      the basis of the biopsy-based test results, the sensitivity of the urinary rapid
      test was 100% and its accuracy (95.2%) was equivalent or superior to that of each
      serum-based ELISA. In addition, no significant differences were observed between
      groups positive and negative on urinary rapid testing in any urinalysis parameter
      examined. The novel urinary rapid test kit evaluated in this study enables
      simple, rapid, and accurate diagnosis of H. pylori infection, and is an ideal
      test method for point-of-care testing.

PMID- 11344533
TI  - Sublimation properties of CoF(3): mass spectrometric and quantum chemical
      studies.
AB  - The sublimation of cobalt trifluoride was studied using the Knudsen effusion
      method combined with mass spectrometry. The pressure of F was directly measured
      for decomposition of CoF(3)(s) into CoF(2)(s). The average kinetic energy of
      CoF(2)(+), CoF(+) and Co(+) fragment ions was determined and the relative
      ionisation cross section curves measured from 6 eV to 100 eV. Thermodynamic
      functions of gaseous CoF(3) and Co(2)F(6), were evaluated from geometrical and
      vibrational parameters provided from theoretical calculations. Heats of formation
      of CoF(3)(s), CoF(3)(g), Co(2)F(6)(g) were established as (-784 +/- 6) kJ/mol, (
      565 +/- 11) kJ/mol and (-1289 +/- 22) kJ/mol, respectively.

PMID- 11344532
TI  - High-throughput cytochrome P450 (CYP) inhibition screening via a cassette probe
      dosing strategy. VI. Simultaneous evaluation of inhibition potential of drugs on
      human hepatic isozymes CYP2A6, 3A4, 2C9, 2D6 and 2E1.
AB  - The inhibition potential of drugs towards five major human hepatic cytochrome
      P450 (CYP) isozymes (CYP2A6, 3A4, 2C9, 2D6, and 2E1) was investigated via
      cassette dosing of the five probe substrates (coumarin, midazolam, tolbutamide,
      dextromethorphan, and chlorzoxazone) in human liver microsomes using a 96-well
      plate format. After microsomal incubations had been terminated with formic acid,
      the five marker metabolites (7-hydroxycoumarin, 1'-hydroxymidazolam, 4
      hydroxytolbutamide, dextrorphan, and 6-hydroxychlorzoxazone) were simultaneously
      quantified using direct injection/online guard cartridge extraction/tandem mass
      spectrometry (DI-GCE/MS/MS). Several advantages resulted from the use of a short
      C(18) guard cartridge (4 mm in length) for DI-GCE/MS/MS, including minimal sample
      preparation, fast online extraction, short analysis time (2.5 min), and minimal
      source contamination. In addition, this method demonstrated an inter-day accuracy
      range from -8.7 - 7.4% with a precision less than 8.3% for the quantification of
      all the marker metabolites. The inhibition assay for the five CYP isozymes was
      evaluated using their known selective inhibitors via individual and cassette
      dosing of the probe substrates. The IC(50) values measured via cassette dosing
      were consistent with those observed via individual dosing, which were all in
      agreement with the reported values. In addition, the validated assay was used to
      evaluate the inhibitory potential of 23 generic drugs (randomly selected) towards
      the five CYP isozymes. The results suggest the integration of the cassette dosing
      strategy and the DI-GCE/MS/MS method can provide a reliable in vitro approach to
      screening the inhibitory potential of new chemical entities, with maximal
      throughput and cost-effectiveness, in support of drug discovery and development.

PMID- 11344534
TI  - A study of the electrospray ionisation and ion-trap fragmentation of [M - H](-)
      ions of new 3,5-disubstituted tetrahydro-2H-1,3,5-thiadiazin-2-thiones.
AB  - The electrospray ionisation (ESI) in negative mode of the pharmacologically
      significant 3,5-disubstituted tetrahydro-2H-1,3,5-thiadiazin-2-thiones, and their
      subsequent fragmentations using an ion-trap mass spectrometer, have been
      investigated. Experiments on sequential product ion fragmentations (MS(n)) were
      performed in order to elucidate the degradation pathways for these compounds. The
      data presented show that the fragmentation of the even-electron [M - H](-) ions
      could proceed through an internal nucleophilic substitution displacement.
      Decarboxylation and extrusion of carbon disulfide are other fragmentations
      observed.

PMID- 11344535
TI  - delta(13)C- and delta(18)O-values of glycerol of food fats.
AB  - The average values of carbon and oxygen isotopic contents (delta(13)C and
      delta(18)O) of 36 glycerol samples from fats have been determined. The examined
      samples arise from many fats of animal and plant origin, as well as from the
      three Italian hard cheeses Parmigiano-Reggiano, Grana Padano and Trentingrana.
      The total (13)C content allows one to distinguish between glycerol from plants
      with the C-4 carbon fixation pathway (maize, mean delta(13)C = -14.4 per
      thousand) and that from plants with the C-3 pathway (mean delta(13)C = -30.7 per
      thousand). The delta(13)C-values of glycerols of animal origin seem to depend on
      the diet of the animal, as suggested by the mean values -29.6, -29.0 and -25.1
      per thousand, respectively, observed for Parmigiano-Reggiano, Trentingrana and
      Grana Padano. Additionally, the mean total (18)O content of glycerol samples of
      vegetable origin is approximately 23.8 per thousand, while that from animal fat
      is 15.1 per thousand. However, the delta(18)O mean values relative to Parmigiano
      Reggiano, Grana Padano and Trentingrana are 11.8, 16.0 and 13.8 per thousand,
      respectively. The combination of the (13)C and (18)O measurements relative to the
      fat glycerol of the three cheeses might be considered a potential criterion of
      authentication.

PMID- 11344536
TI  - Detection of cationic surfactants in oral rinses and a disinfectant formulation
      using matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry.
AB  - Three commercial oral rinses and one commercial disinfectant formulation were
      analyzed for the presence of cationic surfactants using matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) in the
      positive ion mode. The product labels on these formulations indicate the presence
      of cetylpyridinium chloride, tetraalkylammonium or trialkylbenzylammonium
      chlorides. The resulting MALDI-TOF mass spectra only showed cetylpyridinium,
      tetraalkylammonium, and trialkylbenzylammonium ions, apparently due to the
      dissociation of the salts in the ion source. We confirmed the presence of
      cetylpyridinium salt in the three oral formulations, whereas the disinfectant
      formulation consisted of a complex mixture of the salts of
      dioctyldimethylammonium, didecyldimethylammonium, benzylmyristyldimethylammonium,
      decyloctyldimethylammonium, benzyldecyldimethylammonium, and
      benzylcetyldimethylammonium. This work demonstrates again the potential for using
      meso-tetrakis(pentafluorophenyl)porphyrin as a matrix in the MALDI-TOFMS analysis
      of low molecular weight compounds. This study also demonstrates that the mode of
      ionization of quaternary ammonium compounds (cationic surfactant salts) under
      MALDI conditions is by dissociation, leading to the detection of only the
      positively charged moieties.

PMID- 11344537
TI  - Direct determination of glycosylation sites in O-fucosylated glycopeptides using
      nano-electrospray quadrupole time-of-flight mass spectrometry.
AB  - O-Fucosylation is an unusual posttranslational modification present in several
      proteins that play important roles in physiological processes such as
      coagulation, cell signaling and metastasis. Although the exact function of the
      modification is still unclear, the number of proteins found to be modified is
      increasing, and there is a need for further structural and functional analyses.
      Here we report on a rapid and straightforward approach in the analysis of
      glycosylation status and determination of glycosylation sites in O-fucosylated
      glycopeptides using nano-electrospray quadrupole time-of-flight (nano-ESI Q-TOF)
      mass spectrometry. In a single measurement of previously chemically untreated O
      fucosylated peptides originating from the thrombospondin-1 repeats, we were able
      to determine the glycosylation status of the analyzed peptide, the glycosylation
      site, and the glycan structure. The abundance of glycosylated peptide fragment
      ions in MS(2) spectra suggests that nano-ESI Q-TOF mass spectrometry can be used
      as a general approach in structural studies of O-fucosylation in proteins.

PMID- 11344538
TI  - Matrix-assisted laser desorption/ionization mass spectrometric peptide mapping of
      high molecular weight glutenin subunits 1Bx7 and 1Dy10 in Cheyenne cultivar.
AB  - This study describes the verification of the cDNA-deduced amino acid sequences of
      high molecular weight glutenin subunits 1Dy10 and 1Bx7 in Cheyenne cultivar by
      direct matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry (MALDI-TOFMS) analysis of their tryptic fragments omitting
      chromatographic pre-separation. These polypeptides have a conserved structure
      consisting of a long central repetitive domain that prevents the application of
      conventional sequencing procedures such as Edman degradation. The published
      sequence of subunit 1Dy10 contains 7 Lys and 13 Arg residues; thus the production
      of 21 tryptic peptides is expected. The cDNA-deduced sequence for 1Bx7 subunit
      includes 5 Lys and 15 Arg residues, but the presence of three Arg-Pro bonds,
      which are normally not cleaved by trypsin, predicts only 19 tryptic peptides.
      Three different matrices (DHB, SA and HCCA) in combination with the most
      compatible sample preparation procedures were used in order to obtain the maximum
      1Dy10 and 1Bx7 sequence coverage. MALDI analysis of the 1Dy10 tryptic digest
      resulted in the identification of all 21 expected peptides. In the case of 1Bx7
      MALDI analysis resulted in the identification of 17 of the 19 expected peptides,
      giving a sequence coverage of 99.3%. These results were sufficient to rule out
      glycosylation of the 1Dy10 and 1Bx7 proteins and to assess the absence of any
      other post-translational modification, to within the detection limits of the
      method.

PMID- 11344539
TI  - Collision-induced dissociation of MCl(+) adducts (M = Mg, Mn, Zn, Co, Ni and Cu)
      and Cu(+) and Ag(+) adducts of dithioalkyl ketene acetals.
AB  - Electrospray ionization mass spectra of equimolar solutions of dithioalkyl ketene
      acetals 1 and 2 and metal chlorides (MgCl(2), MnCl(2), ZnCl(2), CoCl(2), NiCl(2)
      and CuCl(2)) produced abundant ligated metal ion adducts [1 + MCl](+) and [2 +
      MCl](+). In addition, CuCl(2) also gave rise to Cu(+) adducts. The ligated metal
      ion adducts upon collision-induced dissociation (CID) showed characteristic
      fragmentation pathways reflecting the favoured site of coordination. The results
      show that MgCl(+) prefers oxygen over sulfur, whereas the reverse is true for
      ZnCl(+) adducts, exemplified by the preferred fragmentation of [1 + MgCl](+) as
      elimination of MgCl(OH), while that of [1 + ZnCl](+) is expulsion of
      ZnCl(SCH(3)). Co and Ni chloride adducts tend to give stable metal coordinated
      species. Cleavage of the dithiolane ring followed by elimination of C(2)H(4)S is
      the preferred pathway during the CID of [2 + MCl](+) adducts. The CuCl(+) adducts
      of 1 and 2 showed reduction of Cu((I)) to Cu((0)) resulting in the M(+)(*)ions of
      1 and 2. Abstraction of *CH(3) resulting in elimination of CuCH(3) was observed
      during CID of Cu(+) adducts of 1 and 2. A comparative study of the corresponding
      Ag(+) adducts revealed a similar behaviour.

PMID- 11344540
TI  - Characterization of sodiated glycerol phosphatidylcholine phospholipids by mass
      spectrometry.
AB  - Fast atom bombardment mass spectrometry in the positive mode was used for the
      characterization of sodiated glycerol phosphatidylcholines. The relative
      abundance (RA) of the protonated species is similar to the RA of the sodiated
      molecular species. The sodiated fragment ion, [M + Na - 59](+), corresponding to
      the loss of trimethylamine, and other sodiated fragment ions, were also observed.
      The decomposition of the sodiated molecule is very similar for all the studied
      glycerol phosphatidylcholines, in which the most abundant ion corresponds to a
      neutral loss of 59 Da. Upon collision-induced dissociation (CID) of the [M +
      Na](+) ion informative ions are formed by the losses of the fatty acids in the sn
      1 and sn-2 positions. Other major fragment ions of the sodiated molecule result
      from loss of non-sodiated and sodiated choline phosphate, [M + Na - 183](+), [M +
      Na - 184](+.) and [M + Na - 205](+), respectively. The main CID fragmentation
      pathway of the [M + Na - 59](+) ion yields the [M + Na - 183](+) ion, also
      observed in the CID spectra of the [M + Na](+) molecular ion. Other major
      fragment ions are [M + Na - 205](+) and the fragment ion at m/z 147. Collisional
      activation of [M + Na - 205](+) results in charge site remote fragmentation of
      both fatty acid alkyl chains. The terminal ions of these series of charge remote
      fragmentations result from loss of part of the R(1) or R(2) alkyl chain. Other
      major informative ions correspond to acylium ions.

PMID- 11344541
TI  - Qualitative and quantitative determination of poloxamer surfactants by mass
      spectrometry.
AB  - Poloxamers are polyethylene-polypropylene glycol linear co-polymers. A simple
      matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) method
      has been developed for the determination of the average molecular weight of
      poloxamers. The molecular mass of five standard poloxamers determined by MALDI
      closely corresponds to that specified by the manufacturers, and no mass
      distribution effects were observed. Quantitation of distributions based on the
      molecular mass envelope using electrospray (ES) ionization was unsuccessful. To
      overcome this problem, quantitation was based on fragment ions (m/z 45 and 59)
      which gave reproducible signals using a very high orifice voltage ( approximately
      200 eV). Poloxamer concentrations were determined accurately with a good linear
      response using the standard addition method. We believe that the use of very
      small fragment ions for quantitation of polymers may become a widely applicable
      general technique.

PMID- 11344542
TI  - Supersonic gas chromatography/mass spectrometry.
AB  - A new gas chromatography/mass spectrometry (GC/MS) system was designed and
      evaluated which we have named 'Supersonic GC/MS'. It is based on a modification
      of a commercially available GC/MS system to include a supersonic molecular beam
      (SMB) MS interface. In this system the standard electron ionization (EI) ion
      source was replaced with a fly-through EI ion source mounted in the path of the
      SMB. A hyperthermal surface ionization (HSI) ion source combined with a 90
      degrees ion mirror (for the EI-produced ions) was also added, and placed inside
      the quadrupole mass analyzer in place of its original EI ion source. The
      'Supersonic GC/MS' system requires 18 cm added bench space plus the addition of
      an air-cooled 60 L/s diffusion pump and a 537 L/min rotary pump. The system is
      user friendly since all the gas flow rates, heated zones, sampling and data
      analysis are performed the same way as the original system and are computer
      controlled via the original software. Similar EI sensitivity was obtained as with
      the original system for hexachlorobenzene and octafluoronaphthalene, while
      improved EI detection limits were demonstrated for methyl stearate and eicosane
      due to the significant enhancement of their molecular ion abundances. A GC/MS
      detection limit of 500 ag for pyrene was demonstrated using HSI. Good supersonic
      expansion cooling was achieved with large alkanes, despite the use of a rotary
      pump at the nozzle chamber instead of a diffusion pump. High temperature GC/MS
      analysis was demonstrated for large polycyclic aromatic hydrocarbons (PAHs)
      including ovalene and decacyclene (ten rings). Library searches with EI mass
      spectra are demonstrated, and it is explained why the enhancement of the
      molecular ion actually improves the library search in most cases. The analysis of
      large phthalate esters is also described, and the improvement obtained is shown
      to originate from their enhanced molecular and high mass fragment ions.

PMID- 11344543
TI  - Fast characterization of intact proteins using a high-throughput eight-channel
      parallel liquid chromatography/mass spectrometry system.
AB  - The preparation of protein substrates requires that a large number of
      chromatographic fractions be analyzed for the presence of reactants, products and
      by-products. Analyses using linear matrix-assisted laser desorption/ionization
      mass spectrometry (MALDI-MS) or single column liquid chromatography/mass
      spectrometry (LC/MS) have been inadequate because of mass resolution or
      throughput. Therefore, a high-throughput method employing an eight-channel
      parallel reverse-phase LC/MS system was developed. This system is capable of
      screening fractions from preparative ion-exchange chromatography with the
      required mass accuracy and throughput so that the protein purification process
      can be monitored in a relatively short period of time. As an example, the
      purification and analysis of an acylated protein with a molecular weight of 8.9
      kDa is described and the detection of a contaminating by-product that differs in
      size by less than 20 Da is demonstrated. Using the current instrumentation and
      approach, it is practical to analyze 50 protein-containing fractions from column
      chromatography in less than 1 hour using parallel LC/MS.

PMID- 11344544
TI  - Molecular structure of fulvic acids by electrospray with quadrupole time-of
      flight mass spectrometry.
AB  - Characterisation of the molecular structure of aquatic fulvic acids (FA) has been
      performed using a quadrupole time-of-flight (Q-TOF) mass spectrometer equipped
      with an electrospray ionisation interface. Molecular masses centred around 450 Da
      and sinusoidal spectral distributions have been obtained for all fulvic acids.
      Tandem mass spectrometry (MS/MS) experiments showed losses of 18 Da (H(2)O) and
      44 Da (CO(2)), and possible molecular structures were determined for the first
      time to our knowledge. A methodology is reported for evaluating the average
      elemental composition of FA from high-resolution mass spectra by processing post
      acquisition data calculations using molecular size distributions and atomic
      compositions of ions. The results are found to be consistent with elemental
      analysis data.

PMID- 11344545
TI  - A mass spectrometric study of Al(2)O(3)-SiO(2) melts using a Knudsen cell.
AB  - The thermodynamic activities of SiO(2) in Al(2)O(3)-SiO(2) liquid slags were
      measured by the high-temperature Knudsen cell mass spectromeric method in the
      present work. The measurements were carried out in the temperature range 1863
      2169 K. Tungsten crucibles were used to hold the slags. The system was calibrated
      using a CaF(2) standard. The mass spectra obtained for pure SiO(2) were in
      agreement with earlier data. The activities of silica, measured in the present
      work at 2150 K, show a slight negative deviation at very low alumina mole
      fractions which changed to a positive deviation at higher alumina contents. The
      activity values are in reasonable agreement with the assessment carried out by
      Hillert et al. The results were analysed on the basis of a slag model developed
      earlier at KTH, Stockholm. The present results are found to be compatible with
      the phase diagram proposed by Klug et al.

PMID- 11344546
TI  - Serum heat-labile opsonins in systemic lupus erythematosus.
AB  - To study possible mechanisms responsible for the increased susceptibility to
      infection of patients with active systemic lupus erythematosus (SLE), a study of
      the serum heat-labile opsonic capacity (HLOC) in such patients was undertaken.
      With leukocytes from normal donors, the sera of 12 of 30 patients with active SLE
      demonstrated decreased HLOC for E. coli 075. The phagocytic activity was
      partially restored by normal serum, suggesting that decreased HLOC was
      responsible for the defective phagocytosis. While 8 of 10 patients with active
      SLE and concomitant infections showed deficient opsonic capacity to E. coli 075,
      only 4 of 20 such patients without infections showed the defect (P = 0.01). None
      of 12 patients with inactive disease had deficient opsonic capacity. Similar
      results were obtained with S. aureus 502A as the test bacterium. In the patients
      surviving infection, recovery of normal serum opsonic capacity was rapid and
      usually coincided with an increase of serum complement to normal levels. In three
      patients with active SLE and infection, the causative microorganisms were
      isolated and opsonic capacity for these organisms tested with the individual
      patients' sera. In each case, sera obtained at the onset of the infectious
      episode had low opsonic capacity when compared with normal sera. Serum C3
      proactivator levels were low in 9 of 11 sera with deficient opsonic capacity.
      However, similar low values were found in other SLE sera with normal HLOC,
      suggesting that other factors of the opsonic system were also depleted. Addition
      of the classical complement components C1, C4, C2, C3, and C5 to sera with
      deficient HLOC failed to restore activity. Addition of pure C3 proactivator also
      failed to restore activity. However, addition of C3 proactivator together with 50
      degrees C-heated normal serum restored activity, indicating that factors active
      at the early steps of opsonic activation via the alternative pathway of
      complement were necessary to restore opsonic activity. These findings indicate
      that in active SLE, a decrease of components of the alternate pathway of
      complement activation results in an acquired defect of serum HLOC and perhaps
      other related complement-mediated functions. This defect may be an important
      factor in the increased susceptibility to infections of patients with active
      systemic lupus erythematosus.

PMID- 11344547
TI  - Antibacterial mechanisms of the lower respiratory tract. I. Immunoglobulin
      synthesis and secretion.
AB  - Immunoglobulin synthesis and secretion have been studied in the rabbit lower
      respiratory tract, both in the normal state and after infection with Diplococcus
      pneumoniae or Listeria monocytogenes. In vitro synthesis of immunoglobulin and
      specific antibody was assessed by incorporation of 14C-labeled amino acids into
      protein. Lower respiratory tract secretions and serum were analyzed for
      immunoglobulin and antibody against the infecting organism. Normal respiratory
      tract produced small quantities of immunoglobulin, most of which was IgG. After
      bacterial infection of the lower respiratory tract, there was a marked increase
      in local synthesis of immunoglobulin, especially IgG. Specific antibody of IgG
      class was produced in all lungs infected with listeria by the 11th day, and in
      lungs infected with pneumococcus by the 8th day. Secretions from all normal and
      infected lower respiratory tracts contained IgA and IgG. The IgA to IgG ratios in
      secretions of normal animals, and animals infected with listeria or pneumococcus,
      were 2.3, 2.5, and 2.6, respectively. Sera of animals infected with L.
      monocytogenes contained specific antibody of IgG class but lacked IgA antibody,
      whereas secretions had both IgA and IgG class antibody against listeria.
      Similarly, sera of animals infected with D. pneumoniae had IgG class antibody but
      no IgA antibody, whereas only IgA antibody was found in secretions. The evidence
      that locally synthesized immunoglobulin (especially IgA), including specific
      antibody, is secreted into the lower respiratory tract lumen is discussed.
      Further definition of the role of "local" antibacterial antibody in the
      respiratory tract is of considerable importance.

PMID- 11344548
TI  - Total and effective coronary blood flow in coronary and noncoronary heart
      disease.
AB  - There are no data available concerning total coronary blood flow to the whole
      heart (CBF) in man. "Effective" or "nutrient" coronary blood flow to the whole
      heart (MBF), supposedly a measure of flow through exchanging channels of the
      coronary circulation, has been measured but its validity has not been
      established. Accordingly, CBF and MBF were measured in 9 normal subjects, 26
      patients with coronary heart disease (CHD), and 19 with noncoronary, mostly
      valvular heart disease (NCHD), by coincidence counting 84Rb technique. Two
      methods were used: single bolus (24 cases) and continuous infusion (30 cases).
      Various other parameters including myocardial oxygen utilization (MVO2) and
      lactate extraction ratio were determined. In the normal subjects CBF (386 +/- 77
      ml/min) was significantly higher (P < 0.05) than in CHD (288 +/- 124 ml/min) and
      NCHD (292 +/- 111 ml/min). Likewise the normal MBF (380 +/- 81 ml/min) was
      significantly higher (P < 0.01) than in CHD (251 +/- 105 ml/min) as well as NCHD
      (258 +/- 104 ml/min). The myocardial Rb extraction ratio epsilon Rb) was
      significantly lower in normal subjects (39 +/- 9%) than in CHD (50 +/- 7%) and
      NCHD (52 +/- 11%) and this supports the view that epsilon Rb is flow-dependent.
      In both CHD and NCHD there was significant diminution of MVO2 as well as CBF. In
      CHD this was accompanied by a significant anaerobic trend but in NCHD it was not.
      It might therefore appear that in CHD, MVO2 is determined by perfusion whereas in
      NCHD, perfusion is determined by MVO2. In comparing CBF with MBF by paired
      observation testing, there was no significant difference in the normals (P >
      0.3), whereas the differences were significant in CHD (P < 0.01) and NCHD (P <
      0.02). This was merely a reflection of a reduced ratio of myocardial to total
      body epsilon Rb in CHD and NCHD, and available evidence indicates that this may
      be an expression of depressed transport of Rb+ rather than true shunting.

PMID- 11344549
TI  - Effects of oleic and ricinoleic acids on net jejunal water and electrolyte
      movement. Perfusion studies in man.
AB  - To examine the effects of oleic acid and ricinoleic acid on jejunal absorption,
      steady-state jejunal perfusions were performed in healthy volunteers.
      Taurocholate, used to solubilize the fatty acids, did not influence absorption.
      Both fatty acids (concentration, 10 mM) reversed electrolyte and water net
      movement; that is, they induced fluid secretion; this effect was rapidly
      reversible. Ricinoleic acid (the active principle of castor oil) was the more
      potent, producing fluid secretion when perfused at concentrations at which oleic
      acid was without effect. However, ricinoleic acid was absorbed more slowly than
      was oleic acid, and hence was associated with higher intraluminal concentrations.
      Addition of lecithin and monoolein did not diminish the secretory effect of
      ricinoleic acid; addition of a secretory bile acid (taurodeoxycholate) did not
      enhance the effect. The response of the jejunal mucosa to a known cathartic
      provides observations pertinent to the pathophysiology of steatorrheal diseases
      in man. Dietary fatty acid also has secretory properties with respect to the
      human intestine; bacterial hydration, to hydroxy fatty acids, is not required to
      induce fluid secretion.

PMID- 11344550
TI  - Leukocyte antimicrobial function in patients with leprosy.
AB  - Patients with lepromatous leprosy are unresponsive to lepromin skin-test material
      and possess defective lymphocyte function in vitro, including impaired
      mitogenesis in response to antigens of Mycobacterium leprae. It has been claimed
      that their macrophages cannot digest M. leprae in vitro; such a defect could
      explain both lepromin nonreactivity and impaired lymphocyte function on the basis
      of failure of the afferent limb of the immune response (i.e., defective
      macrophage "processing" of M. leprae). The present studies indicate that
      macrophages from patients with lepromatous and tuberculoid leprosy and from
      normal donors do not differ in their ability to digest heat-killed M. leprae in
      vitro, or in their ability to sustain the viability of M. leprae in tissue
      culture; that monocytes, macrophages, and polymorphonuclear leukocytes of leprosy
      patients and controls possess equivalent microbicidal activity against Listeria
      monocytogenes, Escherichia coli, Proteus vulgaris, Staphylococcus aureus, and
      Candida albicans; and that polymorphonuclear leukocytes from patients with
      lepromatous leprosy iodinate ingested bacteria normally. Whether the basic immune
      defect leading to the development of lepromatous leprosy resides in the
      lymphocyte or in the macrophage remains to be determined. However, the present
      study shows that phagocytic cells from patients with either principal form of
      leprosy function normally in a variety of sophisticated tests of antimicrobial
      function.

PMID- 11344551
TI  - Calcium metabolism of brain in acute renal failure. Effects of uremia,
      hemodialysis, and parathyroid hormone.
AB  - Studies were carried out to evaluate the changes in content of calcium and
      magnesium in brain during acute uremia in dogs. Ca content in gray and white
      matter of brain increased significantly after 3 days of acute uremia and this
      increment was prevented by thyroparathyroidectomy (TPTX). The administration of
      parathyroid extract (PTE) to normal dogs and TPTX uremic animals produced a
      significant rise in brain Ca. These changes were not related to alteration in the
      concentration of Ca in plasma or cerebrospinal fluid, to changes in calcium
      phosphorus product, or to changes in blood pH. Furthermore, the infusion of large
      amounts of phosphate to vitamin D2-treated animals with suppressed parathyroid
      gland activity produced marked elevation in calcium-phosphorus product but no
      significant change in brain Ca. Also, uremia in vitamin D2-treated TPTX dogs
      failed to increase calcium content in brain despite marked elevation in calcium
      phosphorus product. Hemodialysis significantly reduced Ca content of brain but
      the values were still significantly higher than normal. Mg content increased
      modestly only in the white matter of uremic dogs with intact parathyroid glands
      and in normal dogs and TPTX uremic dogs receiving PTE. The results indicate that
      (a) acute uremia of 3 days is associated with a marked rise of Ca content of
      brain and modest increment of Mg in certain parts of the brain, and (b) these
      alterations are not related to uremia, per se, but are dependent on the presence
      of excess parathyroid hormone. It is suggested that the neurological
      abnormalities noted in acute uremia may be related in part to the rise in the Ca
      content of brain.

PMID- 11344552
TI  - Sodium chloride, urea, and water transport in the thin ascending limb of Henle.
      Generation of osmotic gradients by passive diffusion of solutes.
AB  - Studies were designed to examine whether the thin ascending limb of Henle (tALH)
      decreases its luminal solute concentration by an active or a passive transport
      process. In all experiments isolated segments of rabbit tALH were perfused in
      vitro. When tubules were perfused with solutions identical to the bath, active
      transport of NaCl was excluded by the following: (a) osmolality of the collected
      fluid remained unchanged and the same as the bath. (b) net water reabsorption
      could not be demonstrated, and (c) transtubular potential difference was zero.
      Isotopic permeability coefficients (x 10(-5) cm s-1) were calculated from the
      disappearance rate of the respective isotope added to the perfusate. These values
      indicate that tALH is moderately permeable to [14C]urea (6.97 +/- 1.95) while
      having a higher permeability to 22Na (25.5 +/- 1.8) and [not readable: see
      text]Cl (117 +/- 9.1) than any other segment similarly studied. The influx (bath
      to-lumen) isotopic permeabilities were not statistically different from the above
      efflux permeabilities. Osmotic water permeability was immeasurably small. When
      tALH were perfused with a 600 mosmol/liter solution predominantly of NaCl against
      a 600 mosmol/liter bath in which 50% of osmolality was NaCl and 50% urea (to
      simulate in vivo papillary interstitium), the collected fluid osmolality was
      decreased significantly below that of the bath (300 mosmol/liter/mm of tubule).
      The decrease in osmolality was due to greater efflux of NaCl as compared to
      influx of urea. We conclude that active transport of salt by the tALH was not
      detected by the experimental protocol of the current studies, and that the unique
      membrane characteristics of tALH allows for generation of osmotic gradients
      (lumen less concentrated than adjacent surroundings) on purely passive mechanisms
      when perfused with isosmolal salt solutions in a bath with appropriate salt and
      urea concentrations. These findings are consistent with the passive counter
      current model previously proposed from this laboratory.

PMID- 11344553
TI  - Biochemical properties of human glomerular basement membrane in normal and
      diabetic kidneys.
AB  - To determine the presence of any significant structural abnormalities in the
      glomerular basement membrane (GBM) of diabetic individuals, GBM from normal and
      diabetic human kidneys were isolated and analyzed chemically and structurally.
      The amino acid composition of the normal GBM revealed the presence of significant
      amounts of hydroxyproline, hydroxylysine, glycine, and carbohydrate suggesting
      the presence of a collagen-like protein. There was no significant increase in the
      amount of hydroxylysine, hydroxyproline, or in the hydroxylysine-linked glycoside
      glucosyl-galactose in the diabetic kidneys. There was, however, a significant
      decrease in the cystine and sialic acid content of GBM from diabetic kidneys. It
      was further shown that the alpha-chains isolated from the collagens of normal and
      diabetic basement membranes had similar amino acid and carbohydrate compositions.
      The hydroxylysine, hydroxyproline, glycine, and hexose contents were higher by
      82, 56, 74, and 94%, respectively in the alpha-chains compared with the intact
      basement membranes from both the normal and diabetic kidneys. The results
      indicate that the slight increases in hydroxylysine and hexose content observed
      occasionally in diabetic GBM preparations are of no statistical significance and
      cannot be attributed to increases in the activities of enzymes which hydroxylate
      lysine or glycosylate hydroxylysine, respectively.

PMID- 11344554
TI  - Pituitary-testicular responsiveness in male hypogonadotropic hypogonadism.
AB  - An isolated deficiency of pituitary gonadotropins was demonstrated in six 46 XY
      males, 22 to 36 years of age, with and without anosmia. Undetectable or low
      levels of serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH)
      clearly separated hypogonadotropic from normal adult males. Chronic (8-12 wk)
      administration of clomiphene citrate caused no increase in serum FSH or LH in
      gonadotropin-deficient subjects. However, the administration of synthetic
      luteinizing hormone releasing factor (LRF) resulted in the appearance of serum LH
      and, to a lesser degree, serum FSH in three subjects tested. While levels of
      plasma testosterone were significantly lower in gonadotropin-deficient subjects,
      plasma androstenedione and dehydroepiandrosterone were in a range similar to that
      of age-matched normal men. Treatment with human chorionic gonadotropin (HCG)
      increased levels of plasma testosterone to normal adult male values in all
      gonadotropin-deficient subjects. Cessation of treatment with HCG resulted in the
      return of plasma testosterone to low, pretreatment levels. That HCG therapy with
      resultant normal levels of plasma testosterone may somehow stimulate endogenous
      gonadotropin secretion in gonadotropin-deficient subjects was not evident. The
      adult male levels of serum FSH and LH after LRF, and plasma testosterone after
      HCG, confirm pituitary and Leydig cell responsiveness in these subjects.

PMID- 11344555
TI  - A multiple ligand-binding radioimmunoassay of diiodotyrosine.
AB  - A radioimmunoassay has been developed for the measurement of 3,5-diiodo-L
      tyrosine (DIT) in serum. DIT was coupled to porcine thyroglobulin (PTg) with a
      molar ratio of 205:1. Rabbits were immunized with 1 mg of immunogen emulsified in
      complete Freund's adjuvant. Sera were screened for their ability to bind trace
      amounts of [125I]DIT. A serum that bound 40% of the tracer at a final dilution of
      1:1,750 was used in the assay. Assay specificity was improved by the use of
      thyroxine (T4)-binding globulin as a second ligand-binding protein to decrease T4
      and triiodothyronine (T3) cross-reactivity with the antibody. Double antibody and
      polyethylene glycol radioimmunoassays were compared. DIT present in the second
      antiserum shifted the double antibody assay standard curve and altered estimates
      of assay specificity and assay sensitivity. By using the polyethylene glycol
      system and butanol:ethanol extracts of serum, DIT was measured in human serum. In
      35 apparently healthy young adult controls DIT levels averaged 156 ng/100 ml.
      Random DIT levels averaged 158 ng/100 ml in 11 untreated hyperthyroid patients
      and 84 ng/100 ml in 15 untreated primary hypothyroid patients. No diurnal pattern
      in DIT levels could be demonstrated. Thyroid-stimulating hormone administration
      led to a variable but small rise in DIT levels, but short term T3 suppression was
      not associated with a measurable fall in DIT concentrations. Paired serum samples
      from the carotid artery and thyroid vein of 10 euthyroid goiter patients and one
      patient with a toxic solitary adenoma all showed a positive transthyroidal
      gradient indicating the thyroidal release of DIT in each patient. Measurable DIT
      levels of 45, 47, 68, and 80 ng/100 ml, respectively, were found in four fasting
      athyrotic patients indicating that the thyroid is not the only source of serum
      DIT.

PMID- 11344556
TI  - Studies of the hepatic excretory defects in essential fatty acid deficiency.
      Their possible relationship to the genesis of cholesterol gallstones.
AB  - Male hamsters were fed normal and essential fatty acid (EFA)-deficient diets for
      at least 12 wk before bile duct cannulation. With [32P]phosphate, hepatic
      synthesis of lecithin was similar, but biliary excretion of newly synthesized
      lecithin was significantly reduced in EFA-deficient compared to that in normal
      hamsters. Hepatic uptake of intravenously infused taurocholate (TC) and
      taurochenodeoxycholate (TCDC) were similar in both groups of animals. However,
      biliary excretion of intravenously infused TC was significantly reduced in EFA
      deficient hamsters, whereas that of TCDC-was unchanged. The absolute rate of
      biliary cholesterol excretion was similar in both groups. Canalicular bile flow,
      as measured by [14C]erythritol clearance after functional nephrectomy, was
      significantly lower, with both the bile salt-dependent and independent fractions
      of this flow being diminished in EFA-deficient hamsters infused with TC. It is
      concluded that EFA deficiency leads to impaired biliary excretion of
      taurocholate, lecithin, and water, while cholesterol transport is unaffected, and
      thus results in supersaturation of bile with respect to cholesterol and
      production of lithogenic bile.

PMID- 11344557
TI  - The glomerular mesangium. II. Studies of macromolecular uptake in nephrotoxic
      nephritis in rats.
AB  - These studies were designed to explore the effects of nephrotoxic serum (NTS) in
      rats on the uptake and processing by the glomerular mesangium of intravenously
      administered protein macromolecules (radiolabeled aggregated human IgG,
      [125I]AHIgG). Measurements of [125I]AHIgG levels in preparations of isolated
      glomeruli correlated well with qualitative estimates of glomerular IgG deposition
      seen by immunofluorescent microscopy. Rats given 2 ml NTS received 25 mg/100 g
      body wt [125I]AHIgG 48 h later and were sacrificed at varying time intervals
      thereafter. NTS-treated animals demonstrated a marked increase in glomerular
      uptake of [125I]AHIgG as compared with concurrent controls but a normal ability
      to clear [125I]AHIgG from the mesangium over 72 hr. Animals given 1.0, 0.5, and
      0.25 ml NTS had neither proteinuria nor significant light microscopic changes,
      yet had increased uptake of [125I]AHIgG of 4.4, 3.0, and 2.1 times control
      values, respectively at 8 h after the infusion of aggregates. Rats given 1 ml NTS
      and 12.5, 6.25, and 3.125 mg [125I]AHIgG/100 g body wt had increased glomerular
      uptake at 8 h, but there was, within both NTS and control groups, a
      disproportionate decrease in uptake at lower [125I]AHIgG doses. Rats given cobra
      venom factor (CoF) followed by a NTS shown to be complement dependent
      (proteinuria reduced by prior complement depletion with CoF) had less mesangial
      [125I]AHIgG uptake than NTS controls but greater uptake compared with normal
      controls. CoF itself had no effect on mesangial or reticuloendothelial system
      [125I]AHIgG uptake. These studies demonstrate a striking change in glomerular
      mesangial activity after fixation of nephrotoxic antibodies to the glomerular
      basement membrane, even in the absence of proteinuria and suggest that subtle
      alterations of the filtration surface can influence mesangial function. The
      effect of NTS on the mesangium is due, in large part, to the glomerular injury
      and proteinuria which nephrotoxic antibodies produce.

PMID- 11344558
TI  - A study of the abnormal lipoproteins in abetalipoproteinemia.
AB  - The serum lipoproteins of five patients with abetalipoproteinemia (ABL) were
      separated by ultracentrifugation and then analyzed either intact or after
      delipidation. In accord with previous findings, all of the patients lacked serum
      particles with the characteristics of normal low-density lipoproteins (LDL) and
      of the LDL apoprotein as assessed by immunochemical methods. Each patient
      exhibited on every examination an abnormal particle, "LDL", which had the
      flotational properties of LDL, the polypeptide makeup of high-density
      lipoproteins HDL, the spectral and morphological characteristics of neither LDL
      nor HDL, and a relatively low content of cholesteryl esters. The HDL were
      abnormal in having a marked decrease in their total plasma content, an altered
      proportion of the subclasses HDL2 and HDL3, and a peculiar polypeptide
      distribution, comprising both normal and additional components, usually not seen
      in normal controls. The patients also exhibited a decrease of plasma lecithin
      cholesterol acyl transferase (LCAT) activity which probably accounted for the low
      content of cholesteryl esters in both "LDL" and HDL, and in turn for the unusual
      appearance of "LDL" on electron microscopy. It is concluded that ABL is a
      disorder affecting all serum lipoprotein classes. Whether the
      abetalipoproteinemia previously described and noted in the current studies is
      related to or independent of the abnormalities observed in the other lipoproteins
      was not established. How the deficiency of LCAT activity, observed in all
      patients studied, contributed to some of the observed structural lipoprotein
      abnormalities also remained undetermined.

PMID- 11344559
TI  - Factors governing the transepithelial potential difference across the proximal
      tubule of the rat kidney.
AB  - Previous measurements of the transepithelial potential difference (PD) of the
      proximal tubule have yielded widely conflicting values (range -20 to +3 mV). In a
      recent study, Kokko has demonstrated that the PD of the in vitro perfused
      isolated proximal tubule of the rabbit varies in a predictable way from -6 to +3
      mV, depending on the concentration of chloride, bicarbonate, glucose, and amino
      acids in the perfusing solution. The present micropuncture study examines the
      effect of tubular fluid composition on the PD profile along the proximal tubule
      of the in vivo rat kidney. Low resistance measuring electrodes with large tips (3
      5 microns OD) filled with 3 M KCl, were used to provide stable PD recordings.
      Experiments were performed to validate the use of these electrodes.
      Transepithelial PD measurements were made in immediate postglomerular segments
      identified by injection of dye into Bowman's space of accessible surface
      glomeruli and in randomly selected more distal segments of the proximal tubule.
      In the control state, the first loop was found to have a small but consistently
      negative PD which could be obliterated by an infusion of phloridzin. In contrast,
      the PD in later segments was consistently positive. Infusion of acetazolamide
      abolished the positive PD in the later segments. Acetazolamide and glucose
      infusion resulted in a negative PD which was abolished by the additional infusion
      of phloridzin. These data provide evidence that glucose reabsorption is
      electrogenic and can account for the small negative PD normally present in the
      early proximal tubule. The positive PD in later segments appears to be a passive
      chloride diffusion potential. This positive potential is discussed as an
      important electrochemical driving force for significant passive reabsorption of
      sodium in the proximal tubule.

PMID- 11344560
TI  - Renal regulation of acid-base equilibrium during chronic administration of
      mineral acid.
AB  - Previous studies in metabolic alkalosis have demonstrated that two factors are
      the prime determinants of acid excretion and bicarbonate reabsorption; first, the
      diversion to distal exchange sites of sodium previously reabsorbed in the
      proximal tubule and loop of Henle; and, second, a stimulus to sodium-cation
      exchange greater than that produced by a low-salt diet alone. In the present
      study we have examined the hypothesis that these two factors are also the prime
      determinants of acid excretion during the administration of mineral acid loads.
      To test this hypothesis, we have administered to dogs ingesting a low NaCl diet a
      daily dose of 7 meq/kg of H+ with anions (chloride, sulfate, or nitrate) whose
      differing degrees of reabsorbability influence the speed and completeness with
      which each is delivered to the distal nephron with its accompanying Na+. After 2
      3 wk of acid administration, and after an initial urinary loss of Na+ and K+, the
      steady-state value for plasma [HCO3-] was 8.6 meq/liter below control in the HCl
      group, 3.7 meq/liter below control in the H2SO4 group, and unchanged from control
      in the HNO3 group; all of these values were significantly different from each
      other. We would propose the following explanation for our findings: when HCl is
      administered chronically, marked acidosis occurs because distal delivery of Cl-
      is restricted by the ease with which the Cl- can be reabsorbed in the proximal
      portions of the nephron. Only when Cl- retention produces sufficient
      hyperchloremia to insure delivery of Na+ (previously reabsorbed in proximal
      tubule and loop of Henle) to the distal nephron in quantities equal to ingested
      Cl is this primary constraint removed. In the case of sulfuric and nitric acids,
      there is no constraint on distal delivery, the nonreabsorbability of the
      administered anion causing prompt, total delivery of Na+ to exchange sites in
      quantities equal to administered hydrogen. Thus, with H2SO4 and HNO3 the sole
      constraint on removal of the acid load is the inability of the distal exchange
      mechanism to conserve the Na+ increment fully by means of H+ exchange. Escape of
      Na+ and K+ into the urine and the resulting stimulus to Na(+)-H+ exchange remove
      this constraint and are responsible for establishment of a new steady-state of
      acid-base equilibrium at plasma [HCO3-] levels significantly higher than those
      seen with HCl. The feeding of HCl in the presence of a normal salt intake led to
      a degree of metabolic acidosis not significantly different from that seen in dogs
      ingesting a low-salt diet. We suggest that the presence of dietary sodium at
      distal exchange sites did not enhance acid excretion because it is only after a
      loss of body sodium stores that sodium avidity is increased sufficiently to allow
      full removal of the acid load. The present findings indicate that the fundamental
      factors controlling acid excretion and bicarbonate reabsorption in metabolic
      acidosis are closely similar to those operative in metabolic alkalosis.

PMID- 11344562
TI  - An in vitro model of gluten-sensitive enteropathy. Effect of gliadin on
      intestinal epithelial cells of patients with gluten-sensitive enteropathy in
      organ culture.
AB  - Jejunal biopsy specimens from patients with gluten-sensitive enteropathy (GSE)
      (obtained during gluten challenge) as well as from normal individuals and
      patients with other gastrointestinal abnormalities were cultured in vitro for 48
      h in the presence or absence of a peptic-tryptic digest (P-T digest) of gliadin.
      In the absence of gliadin the alkaline phosphatase activity in the biopsy
      specimens obtained from normal control individuals increased from an initial
      value of 384 +/- 83 U to a 48 h value of 561 +/- 151 U (mean +/- SD) (difference
      significant at P < 0.01). The initial alkaline phosphatase activity of specimens
      obtained from patients with GSE was strikingly lower than that of normals, 117 +/
      79 U, and increased to a 48 h value of 399 +/- 203 U (difference significant at
      P < 0.01). The biochemical change in cultured biopsy specimens of GSE patients
      correlated with increases in the length and regularity of brush borders of
      epithelial cells as seen with the electron microscope. In the presence of a P-T
      digest of gliadin, the alkaline phosphatase activity of biopsy specimens of
      control individuals increased from an initial value of 384 +/- 83 U to a 48 h
      value of 578 +/- 156 U. In contrast, the alkaline phosphatase activity of biopsy
      specimens of patients with GSE in exacerbation showed a markedly diminished
      increase in activity during 48 h of culture; in this case the initial activity
      was 117 +/- 79 U and the final activity was 203 +/- 93 U. This inhibitory effect
      on increase of alkaline phosphatase activity during organ culture was specific in
      that a P-T digest of casein (a protein not toxic in vivo to patients with GSE)
      had no effect on alkaline phosphatase increases in culture. Finally, these
      results obtained with biopsy specimens taken from patients with GSE in
      exacerbation were compared with results obtained from patients with GSE in
      remission. Alkaline phosphatase activity of specimens obtained from the latter
      group of patients also increased during culture but in this instance P-T digest
      of gliadin in the culture medium had no significant inhibitory effect. In
      conclusion, the inhibitory effect of gliadin on intestinal epithelial cells in
      organ culture represents an in vitro model of gluten-sensitive enteropathy.
      Inasmuch as this effect of gliadin is not seen in cultures of specimens taken
      from patients in remission, it appears that gliadin is not directly toxic to GSE
      jejunal mucosa per se, but rather toxicity requires the participation of an
      endogenous effector mechanism which must first be stimulated in vivo.

PMID- 11344561
TI  - Cytoplasmic receptor for glucocorticoids in lung of the human fetus and neonate.
AB  - In fetal animals, glucocorticoids accelerate development of the lung and cause
      precocious appearance of alveolar surfactant. To determine if the human lung also
      can respond to corticosteroids, we examined lungs of the human fetus and neonate
      for both cytoplasmic binding and nuclear uptake of glucocorticoids. In slices of
      fetal lung incubated with [3H]dexamethasone at 2 degrees C, specific
      macromolecular binding occurs primarily in the "cytoplasmic" fraction. After
      further incubation at 37 degrees C. nearly 75% of the radioactivity localizes in
      the "nuclear" fraction with a concentration of 0.3 pmol/mg DNA at apparent
      dexamethasone saturation (47 nM). The cytoplasmic receptor binds dexamethasone in
      vitro with high affinity (dissociation constant = 8.9 nM), and the affinity of
      various other steroids correlates with their glucocorticoid potency. Receptor was
      present in lungs of fetuses and neonates of gestational age 12-43 wk, with a mean
      concentration in hysterotomy specimens of 0.24 pmol sites/mg cytosol protein.
      Similar binding activity was present at lower concentration in fetal liver, gut,
      kidney, heart, muscle, and skin. Cytoplasmic receptor was not detected in lung
      and liver of premature infants with respiratory distress syndrome. This deficit
      appears to result from increased levels of endogenous steroids (mean cortisol
      45.5 micrograms/100 ml cytosol) as well as inactivation of receptor secondary to
      the illness. Thus, the lung of the human fetus and neonate contains the receptor
      mechanism necessary for direct responsiveness to glucocorticoids. These findings
      support the potential usefulness of these hormones in prevention of respiratory
      distress syndrome in the premature infant.

PMID- 11344563
TI  - Proximal tubule reabsorption after hyperoncotic albumin infusion. Role of
      parathyroid hormone and dissociation from plasma volume.
AB  - Preferential expansion of the plasma volume by infusion of salt-poor hyperoncotic
      albumin solution decreases sodium reabsorption by the proximal tubule. The
      present micropuncture studies test the thesis that albumin infusion depresses
      proximal reabsorption by an effect unrelated to expansion of the plasma volume,
      perhaps due to an effect of parathyroid hormone (PTH) on proximal sodium
      reabsorption. Infusion of salt-poor hyperoncotic albumin significantly decreased
      plasma ionized calcium, increased immunoreactive PTH (iPTH) in plasma, decreased
      sodium reabsorption by the proximal tubule, and increased phosphate clearance. In
      contrast, infusions of albumin, in which the ionized calcium was restored to
      normal plasma levels, had no significant effect on ionized calcium, iPTH,
      proximal reabsorption, or phosphate clearance in intact dogs. Similarly, in
      parathyroidectomized animals given a constant replacement infusion of PTH,
      albumin infusion had no significant effect on proximal reabsorption or phosphate
      clearance. Plasma volume was markedly expanded following albumin infusion in all
      groups of dogs. These findings (a) indicate that PTH plays a significant role in
      the decrease in sodium reabsorption by the renal proximal tubule after salt-poor
      hyperoncotic albumin infusion, and (b) dissociate preferential expansion of the
      plasma volume from decreases in sodium reabsorption by the proximal tubule.

PMID- 11344564
TI  - Ketone-body production and oxidation in fasting obese humans.
AB  - Rates of plasma acetoacetate and total ketone-body production and oxidation to
      CO2 were determined by an isotope tracer technique in eight obese subjects
      undergoing progressive starvation. After a brief fast and under conditions of
      mild ketonemia and minimal ketonuria, rates of acetoacetate and total ketone-body
      production and oxidation were directly related to the increasing plasma
      concentration. After a longer fast and with severer ketonemia, acetoacetate and
      total ketone-body production and oxidation rates were higher but became constant
      and unrelated to the plasma concentrations. The maximum rates of total ketone
      body production and oxidation were about 150 g/24 h and 129 g/24 h, respectively.
      Although an increased ketone-body production was the primary factor responsible
      for the hyperketonemia, an imbalance between production and removal of the ketone
      bodies cannot be excluded. Such an imbalance could account, at least in part, for
      the developing hyperketonemia and for the lack of relationship between production
      rates and plasma concentrations.

PMID- 11344565
TI  - Distal tubular feedback in the autoregulation of single nephron glomerular
      filtration rate.
AB  - Renal clearance and recollection micro-puncture experiments were conducted to
      evaluate the possible role of a distal tubular feedback mechanism in the
      phenomenon of renal autoregulation in dogs. Single nephron glomerular filtration
      rate (SNGFR) was measured from collection sites in both the proximal (proximal
      SNGFR) and distal tubules (distal SNGFR). Single nephron autoregulatory behavior
      was assessed by evaluating the response of SNGFR to a reduction in renal arterial
      pressure imposed by means of an aortic constrictor. Whole kidney function was
      evaluated by parallel measurements of renal blood flow and inulin clearance.
      Whole kidney autoregulation was observed when renal arterial pressure was
      decreased from 141 +/- 3 (SE) mm Hg to 101 +/- 2 mm Hg; renal blood flow and GFR
      were not significantly altered from control values of 3.76 +/- 0.2 ml/min.g and
      0.69 +/- 0.04 ml/min.g kidney weight, respectively. In 11 autoregulating
      preparations, proximal transit time was likewise unchanged from the control value
      of 26 +/- 2 s, indirectly suggesting that the superficial nephrons also
      participated in the autoregulatory response. However, proximal SNGFR decreased
      significantly from 88 +/- 7 nl/min to 66 +/- 6 nl/min, a reduction which was
      proportional to the decrease in arterial pressure. In 14 dogs in which both
      proximal SNGFR and distal SNGFR were measured at control blood pressure (136 +/-
      5 mm Hg), distal SNGFR was 47 +/- 4 nl/min, a value significantly lower than that
      for proximal SNGFR (79 +/- 6 nl/min). In contrast to the results based upon
      proximal collections, distal SNGFR was not significantly altered following aortic
      constriction (44 +/- 5 nl/min vs. 47 +/- 5 nl/min) therefore exhibiting
      autoregulation in association with that observed for the whole kidney. These
      experiments indicate that though superficial nephrons do possess autoregulatory
      capability, interruption of distal delivery due to complete collection from the
      proximal tubule interferes with that nephron's ability to manifest an
      autoregulatory response. They support the concept that a feedback mechanism,
      related to some function of distal delivery, is of significance in the intrinsic
      regulation of SNGFR. The data further suggest that quantitative estimates of
      SNGFR based on complete proximal collections may not be representative of those
      throughout the superficial cortex of the dog, at least in certain experimental
      circumstances.

PMID- 11344566
TI  - Glucose reabsorption from bile. Evidence for a biliohepatic circulation.
AB  - Glucose is absent from human bile and present in low concentrations in bile from
      the rat. To study the mechanisms of this blood-bile glucose concentration
      difference, infusions of glucose were administered i.v. to 300-400 g male Sprague
      Dawley rats with ligated renal pedicles and to two postcholecystectomy patients
      with indwelling t-tubes. Glucose was assayed in plasma, bile, and rat liver by a
      hexokinase method specific for D-glucose. In man, glucose was detected in bile
      when plasma glucose increased above 350 mg/100 ml. In animals studies, low
      concentrations of bile glucose were observed at plasma levels between 100 and 300
      mg/100 ml. However, when plasma concentrations increased between 400 and 900
      mg/100 ml, glucose appeared more rapidly in bile, defining by extrapolation an
      apparent plasma glucose threshold of 280 mg/100 ml. Intraportal phlorizin, a
      competitive inhibitor of glucose transport, significantly increased bile glucose
      concentrations. Plasma-bile concentration differences were also observed in rats
      after i.v. [3-14C]O-methyl glucose (3-O-MG) but not after [3H]mannitol. Hepatic
      glucose levels were never lower than plasma levels and liver-plasma 3-O-MG ratios
      were 0.92 +/- 0.22 indicating that entry of glucose and 3-O-MG into hepatocyte
      water was not limiting. Furthermore, when sodium dehydrocholate augmented
      canalicular secretion, biliary glucose excretion increased proportionally
      suggesting that glucose entry into bile was not impeded. When estimates of
      hepatic glucose secretion were compared with biliary glucose excretion, the
      latter increased progressively when estimated secretion rates exceeded 50
      micrograms/min or when phlorizin was given. Finally, during bile stop-flow
      experiments, [3-14C]O-MG and [14C]glucose were selectively removed from bile
      compared with [3H]mannitol. The findings suggest that glucose and 3-O-MG are
      reabsorbed from bile after entry at the hepatocyte, accounting for their low bile
      plasma ratio. The biliary glucose transport process may be described by Michaelis
      Menten kinetics and is analogous to recently defined kinetics for renal tubular
      reabsorption of glucose. These studies provide evidence that certain products of
      bile secretion may undergo a "biliohepatic" circulation.

PMID- 11344567
TI  - Interaction of immunoglobulins with liposomes.
AB  - Liposomes were used as model targets to test the effect of immunoglobulins on
      biomembranes. Heat-aggregated immunoglobulins (Ig) exceeded native
      immunoglobulins in their capacity to release anions and glucose from model
      liposomes (either lecithin-dicetyl-phosphate-cholesterol or lecithin-stearylamine
      cholesterol in molar ratios of 7:2:1). This interaction was not dependent upon
      the presence of cholesterol in the membrane. Mild heat-aggregation (10 min at
      61.5 degrees C) increased the membrane-perturbing activity of certain Ig.
      Activity varied among classes and subclasses: IgG1 > pooled IgG > IgG4 > IgA1 >
      IgG3. IgG2, IgA2 and IgM were inert. Fc fragments of IgG were as active as IgG1,
      whereas Fab fragments were inactive. Prolonging aggregation to 60 min destroyed
      the activity of Ig. Membrane-activity could not be induced in non-Ig molecules
      (such as bovine serum albumin) by 10 or 60 min heat-aggregation. Density gradient
      centrifugation of IgG1 molecules indicated that membrane perturbing activity was
      associated with 15-20-s aggregates. Sepharose 4B chromatography demonstrated
      preferential interaction between cationic membranes and aggregated Ig, whereas
      anionic membranes interacted nonselectively with both native and aggregated Ig
      via salt-like interactions. One explanation for these data is that heat
      aggregation induces a conformational change in the Fc regions of certain Ig
      permitting them to interact with liposomes, presumably by enhancing their
      hydrophobic associations with membrane phospholipids.

PMID- 11344568
TI  - Hereditary deficiency of the sixth component of complement in man. I.
      Immunochemical, biologic, and family studies.
AB  - An 18-yr-old black woman in good general health was found to lack serum hemolytic
      complement activity. The sixth component of complement (C6) was undetectable by
      functional assay of serum or plasma and by immunoprecipitin analysis of serum.
      Functional titers of all other complement components were normal. The absence of
      C6 in the patient's serum could not be accounted for by a circulating C6
      inhibitor, and addition of functionally pure C6 to the patient's serum restored
      hemolytic activity to normal. Both parents of the proband and five of six
      available siblings had approximately half the normal levels of functional C6. The
      other sibling had a normal C6 level. These data suggest that both parents and
      five siblings are heterozygous for C6 deficiency, while the proband is homozygous
      and one sibling is normal. Thus, C6 deficiency appears to follow classic
      mendelian inheritance, with all three possible genotypes recognizable within the
      family. Functional properties of the proband's C6-deficient serum included total
      absence of bactericidal activity against Salmonella typhi 0 901 and Hemophilus
      influenzae, type b, and inability to mediate lysis of red blood cells from
      patients with paroxysmal nocturnal hemoglobinuria in either the acidified serum
      or "sugar water" tests. The proband's serum did, however, exhibit a normal
      capacity (a) to generate chemotactic activity during incubation with bacterial
      endotoxin or aggregated IgG, (b) to mediate the immune adherence phenomenon, and
      (c) to coat human red blood cells, sensitized by cold agglutinins, with C4 and
      C3.

PMID- 11344569
TI  - Hereditary deficiency of the sixth component of complement in man. II. Studies of
      hemostasis.
AB  - Prompted by previous observations of defective blood clotting in rabbits
      deficient in the sixth component of complement (C6), an evaluation was made of
      the hemostatic functions of the homozygous proband of a newly recognized human
      kindred with hereditary C6 deficiency. This human subject, who had no clinical
      evidence of a bleeding disorder, exhibited a total lack of C6 by functional and
      immunoprecipitin assays of serum or plasma. Standard tests of hemostatic function
      were normal; however, when the whole blood clotting time was measured at 25
      degrees C in plastic tubes, it was at the upper range of our normal values. In
      confirmation of this observation, prothrombin consumption, when performed at 37
      degrees C in plastic tubes, was at the lower range of normal. Inulin and
      endotoxin, in concentrations shown to cause activation of human complement, had
      little or no effect on clotting times or prothrombin consumption of normal or C6
      deficient human blood. These observations indicate that absence of C6 does not
      have a significant effect on hemostatic function in man. In the light of other
      investigations, the observed differences in clotting function between C6
      deficient human blood and C6-deficient rabbit blood could be due to species
      differences governing the susceptibility of platelets to complement activation.

PMID- 11344570
TI  - Activation of human blood monocytes by products of sensitized lymphocytes.
AB  - Studies were carried out to determine whether products of activated human
      lymphocytes altered human monocyte function. Supernatants from sensitized human
      lymphocytes stimulated by specific antigen were cultured with monolayers of human
      monocytes. Such monocytes exhibited enhanced adherence to their culture vessels
      and increased glucose carbon-1 oxidation after 2-3 days of incubation. The
      substance responsible for these effects was found to elute from Sephadex G-100
      gel columns in a fraction with 23,000 mol wt, the same fraction containing human
      migration inhibitory factor.

PMID- 11344571
TI  - Human lymphocyte subpopulations. Effect of corticosteroids.
AB  - Normal subjects given 60 mg of prednisone orally at 8:00 a.m. developed a
      transient lymphopenia at 2:00 p.m. To define the populations of lymphocytes
      affected the number and type of lymphocytes in the peripheral blood were assayed.
      "Late" and "early" spontaneous sheep red blood cell rosettes were used as markers
      for thymus-derived (T) lymphocytes and one of its subpopulations, respectively.
      Receptors for aggregated gammaglobulin and complement identified bursal
      equivalent or bone marrow-derived (B) lymphocytes and one of its subpopulations,
      respectively. 6 h after administration of 60 mg of prednisone, the blood samples
      showed a decrease in proportion of T cells from 69.2 +/- 2.1% to 55.9 +/- 2.8%
      (average +/- SE) and an increase in B-cell proportion from 21.3 +/- 2.0% to 44.8
      +/- 4.1%. The changes of "early" rosettes and complement receptor lymphocytes
      also paralleled these. In all cases the absolute numbers of T cells and of B
      cells were decreased by prednisone. The density gradient distribution of the
      lymphocytes did not change after prednisone. These data indicate that both T and
      B lymphocytes are affected by the prednisone but that the T cell lymphopenia was
      more pronounced. The lymphopenia might reflect either sequestration in the marrow
      and/or transient arrest of recirculation.

PMID- 11344572
TI  - Role of the pituitary and thyroid glands in the decline of minimal O2 consumption
      with age.
AB  - Resting O2 consumption rate (BMR) or minimal O2 consumption rate (MOC) declines
      with age. Data are presented that suggest that a newly described function of the
      pituitary may be responsible for a considerable part of the total 75% decline in
      the MOC with age. The new function appears to decrease the responsiveness of
      peripheral tissues to thyroid hormones. Response curves to injected thyroxine
      indicated that immature rats were three times more responsive to thyroxine than
      adult rats. All the major endocrine ablations were performed in this and earlier
      work, and only pituitary ablation (a) restored in adults part of the
      responsiveness to thyroxine found in immature rats and (b) arrested the normal
      age-associated decrease in responsiveness to thyroxine in immature rats. Bovine
      pituitary extracts were found that decreased the responsiveness of immature rats
      to thyroxine. Experiments with the new pituitary function suggested a possible
      endocrine mechanism to explain why partial starvation doubled the lifespan for
      rats only when started before puberty.

PMID- 11344573
TI  - Splanchnic glucose and amino acid metabolism in obesity.
AB  - Arterial concentrations and splanchnic exchange of glucose, lactate, pyruvate,
      glycerol, free fatty acids, and individual acidic and neutral amino acids were
      determined in obese and nonobese control subjects in the basal state and during a
      45 min infusion of glucose. Glucose was administered to the controls at a rate (2
      mg/kg/min; 144 +/- 4 mg/min) known to inhibit splanchnic glucose output without
      influencing peripheral glucose utilization. The obese subjects received glucose
      at two dose levels (75 and 150 mg/min) which simulated either the rise in insulin
      or the inhibition in splanchnic glucose production observed in the controls. In
      the basal state splanchnic glucose production did not differ significantly
      between obese and control subjects. However splanchnic uptake of lactate,
      glycerol, alanine, free fatty acids, and oxygen was 50-160% greater in obese
      subjects. Splanchnic uptake of glucose precursors could account for 33% of
      hepatic glucose output in the obese group as compared to 19% in controls. The
      increase in alanine and lactate uptake was due in part, to a 50% increase in
      splanchnic fractional extraction. Administration of glucose to the control
      subjects 144 +/- 4 mg/min) resulted in a 50-60% increment in arterial insulin and
      a 75% reduction in splanchnic glucose output. In the obese group, infusion of
      glucose at a rate of 75 mg/min resulted in an equivalent rise in arterial
      insulin, but was accompanied by a less than 40% inhibition in splanchnic glucose
      output. Glucose infusion at a rate of 150 mg/min in the obese resulted in a 75%
      reduction in splanchnic glucose output which was equivalent to that observed in
      controls, but was accompanied by a significantly greater rise (100-200%) in
      arterial insulin. It is concluded that in obesity (a) despite basal
      hyperinsulinemia, splanchnic uptake of glucose precursors is increased, the
      relative contribution to total glucose release attributable to gluconeogenesis
      being 70% higher than in controls; (b) infusion of glucose at rates causing
      equivalent increases in arterial insulin induces a smaller inhibition in
      splanchnic glucose output than in controls; (c) infusion of glucose at rates
      causing comparable inhibition in splanchnic glucose output is accompanied by a
      disproportionately greater increase in endogenous insulin than in controls. These
      data are compatible with hepatic resistance to insulin in obesity.

PMID- 11344574
TI  - Stimulation of human neutrophil leukocyte aerobic glucose metabolism by purified
      chemotactic factors.
AB  - The interaction of human neutrophils adherent to plastic petri dishes with the
      purified chemotactic factors C5a and kallikrein increased their rate of aerobic
      glycolysis 25-120% and the activity of their hexose monophosphate shunt (HMPS)
      100-600%, reaching a plateau after 2 hr at 37 degrees C. The stimulation of
      either pathway required a chemotactically active stimulus since neither C5 nor
      prekallikrein or inactivated kallikrein could enhance metabolic activity. Marked
      suppression of the neutrophil chemotactic response by preincubation with a
      chemotactic factor to achieve deactivation, 5 x 10(-7) M diisopropyl
      fluorophosphate, or the neutrophil immobilizing factor (NIF) did not prevent the
      stimulation of HMPS activity or glycolysis by chemotactic factors. The metabolic
      inhibitors iodoacetate and 6-aminonicotinamide at concentrations which blocked
      enhancement of glycolysis or HMPS activity, respectively, partially suppressed
      the chemotactic response of neutrophils to the chemotactic factors. The capacity
      of a chemotactic factor to stimulate glucose metabolism of human neutrophils is
      associated with a maximal chemotactic response, but this stimulation is not alone
      sufficient for chemotaxis.

PMID- 11344576
TI  - Increased formation of ursodeoxycholic acid in patients treated with
      chenodeoxycholic acid.
AB  - The formation of ursodeoxycholic acid, the 7 beta-hydroxy epimer of
      chenodeoxycholic acid, was investigated in three subjects with cerebrotendinous
      xanthomatosis and in four subjects with gallstones. Total biliary bile acid
      composition was analyzed by gas-liquid chromatography before and after 4 months
      of treatment with 0.75 g/day of chenodeoxycholic acid. Individual bile acids were
      identified by mass spectrometry. Before treatment, bile from cerebrotendinous
      xanthomatosis (CTX) subjects contained cholic acid, 85%; chenodeoxycholic acid,
      7%; deoxycholic acid, 3%; allocholic acid, 3%; and unidentified steroids, 2%;
      while bile from gallstone subjects contained cholic acid, 45%; chenodeoxycholic
      acid, 43%; deoxycholic acid, 11%, and lithocholic acid, 1%. In all subjects, 4
      months of chenodeoxycholic acid therapy increased the proportion of this bile
      acid to approximately 80% and decreased cholic acid to 3% of the total biliary
      bile acids, the remaining 17% of bile acids were identified as ursodeoxycholic
      acid. After the intravenous injection of [3H]chenodeoxycholic acid, the specific
      activity of biliary ursodeoxycholic acid exceeded the specific activity of
      chenodeoxycholic acid, and the resulting specific activity decay curves suggested
      precursor-product relationships. When [3H]7-ketolithocholic acid was
      administrated to another patient treated with chenodeoxycholic acid,
      radioactivity was detected in both the ursodeoxycholic acid and chenodeoxycholic
      acid fractions. These results indicate that substantial amounts of
      ursodeoxycholic acid are formed in patients treated with chenodeoxycholic acid.
      The ursodeoxycholic acid was synthesized from chenodeoxycholic acid presumably
      via 7-ketolithocholic acid.

PMID- 11344575
TI  - Fibrinogen Philadelphia. A hereditary hypodysfibrinogenemia characterized by
      fibrinogen hypercatabolism.
AB  - A new, autosomally inherited abnormal fibrinogen associated with
      hypofibrinogenemia has been described in several members of a family. Plasma
      fibrinogen measured either as thrombin-clottable protein or by immunodiffusion
      revealed a fibrinogen level ranging between 60 and 90 mg/100 ml. The thrombin
      time of plasma or purified fibrinogen was prolonged and only partially corrected
      by the addition of calcium. Purified fibrinogen prolonged the thrombin time of
      normal plasma. Fibrinopeptide release by thrombin was normal in rate and amount,
      but fibrin monomer aggregation was grossly disturbed, especially in a high ionic
      strength medium. We have designated this fibrinogen "fibrinogen Philadelphia."
      Acrylamide gel electrophoresis of mixtures of [121I]normal and [125I]abnormal
      fibrinogens revealed a slight increase in the anodal mobility of fibrinogen
      Philadelphia. Similarly, DEAE-cellulose chromatography showed slightly stronger
      binding of fibrinogen Philadelphia than normal. To elucidate the mechanism
      responsible for the low plasma fibrinogen concentration, simultaneous metabolic
      studies of autologous (patient) and homologous (normal) fibrinogen, labeled with
      125I and 121I, respectively, were performed in two affected subjects. Autologous
      fibrinogen half-life was short and the fractional catabolic rate was markedly
      increased in both family members. In contrast, homologous fibrinogen half-life
      and fractional catabolic rate were normal. These metabolic studies demonstrate
      that rapid degradation of fibrinogen Philadelphia is largely responsible for the
      depressed levels of a plasma fibrinogen. This represents the first example of a
      mutant plasma protein in which the molecular defect is associated with an altered
      catabolism.

PMID- 11344577
TI  - Fletcher factor deficiency. A diminished rate of Hageman factor activation caused
      by absence of prekallikrein with abnormalities of coagulation, fibrinolysis,
      chemotactic activity, and kinin generation.
AB  - Fletcher factor-deficient plasma is deficient in prekallikrein and therefore
      generates no bradykinin upon activation with kaolin. It also possesses a
      diminished rate of kaolin-activable coagulation and fibrinolysis and possesses a
      defect in kaolin-activable chemotactic activity. These abnormalities are also
      corrected by reconstitution with purified prekallikrein. Addition of intact
      activated Hageman factor corrected the coagulation, fibrinolytic, and chemotactic
      defects and addition of Hageman factor fragments corrected the fibrinolytic
      defect and partially corrected the chemotactic defect; neither of these corrected
      the kinin-generating defect. Although the Hageman factor-dependent pathways
      appear to be initiated by contact activation of Hageman factor, the kallikrein
      generated activates more Hageman factor; this feedback is necessary for the
      Hageman factor-dependent pathways to proceed at a normal rate. It is the absence
      of this feedback in Fletcher factor-deficient plasma that accounts for the
      diminished rate of activation of Hageman factor and therefore a diminished rate
      of activation of the coagulation and fibrinolytic pathways. The ability of
      prekallikrein to correct the coagulation, fibrinolytic, kinin-generating, and
      chemotactic defects of Fletcher factor-deficient plasma is consistent with the
      identity of the Fletcher factor and prekallikrein.

PMID- 11344578
TI  - Uptake of materials by the intact liver. The exchange of glucose across the cell
      membranes.
AB  - D-Glucose equilibrates within liver cells. We have studied its process of entry
      into and exit from these cells with the multiple indicator dilution technique.
      Labeled red cells (a vascular indicator), labeled sucrose (an extracellular
      reference), and labeled D-glucose were rapidly injected into the portal vein, and
      from serially sampled hepatic venous blood, normalized outflow-time patterns were
      obtained. The labeled red cell curve rises to an early high peak, and decays
      rapidly; and that for sucrose reaches a later and lower peak and decays less
      rapidly, but generates an equivalent area. The curve for labeled D-glucose begins
      with that for labeled sucrose, gradually rises to a peak which is later and
      substantially lower than that for sucrose, and then decreases slowly. At high
      glucose levels this curve assumes a squared-off shape, rises fairly quickly to
      its highest level, at the time of the sucrose peak, and then slowly decreases.
      Phlorizin and galactose infusion result in the emergence of a pronounced early
      peak, under the sucrose peak; and the curve for tracer L-glucose approaches that
      for sucrose. We resolve from the D-glucose curves, by model analysis, two
      components: throughout material, which has not entered the cells; and exchanging
      material, which has entered and later returned to the circulation. The analysis
      provides estimates of the kinetic entrance and exist coefficients; and from
      these, saturation of both the entrance and exit processes was evident. The
      characteristic transport parameters were determined. For both entrance and exit,
      a common Km, 2,170 mg/100 ml, and transport maximum, 5.13 mg s-1 (ml
      intracellular fluid)-1, were found. Both these values are exceedingly large.
      Several other phenomena were defined which additionally characterize the
      transport process: phlorizin and galacose produced competitive inhibition; the
      transport process was found to be relatively stereospecific; and sudden infusion
      of hypertonic glucose produced counter-transport of labeled D-glucose.

PMID- 11344579
TI  - Stimulation of heme oxygenase in macrophages and liver by endotoxin.
AB  - In rat peritoneal macrophages, engaged in erythrophagocytosis in vitro, endotoxin
      stimulated heme oxygenase (HO) activity, which was additive to the substrate
      mediated enzyme induction produced by the ingested erythrocyte hemoglobin.
      Endotoxin neither appeared to injure the erythrocytes, nor did it enhance the
      rate of erythrophagocytosis. In intact rats, HO activity in both parenchymal and
      sinusoidal cells of the liver was increased after treatment with endotoxin. It is
      likely that endotoxin directly stimulates HO activity, a process which may
      account for the reported rise in bilirubin formation in endotoxin-treated
      animals. The effect of endotoxin on HO may represent part of the general
      activation of phagocytic cells by endotoxin.

PMID- 11344580
TI  - Augmentation of prolactin secretion by estrogen in hypogonadal women.
AB  - The effect of estrogen on prolactin (PRL) release and gonadotropin suppression
      was assessed in six experiments performed on four hypogonadal women. Ethinyl
      estradiol at a dose of 1 microgram/kg per day induced a significant elevation of
      serum PRL levels within the 1st wk of treatment. There was a further rise until a
      plateau was reached in about 3-4 wk to levels of more than 3 times the initial
      concentration. This was accompanied by a pattern of increased episodic
      fluctuation. The corresponding serum luteinizing hormone and follicle-stimulating
      hormone fell progressively during the study period. These data indicate that a
      positive feedback relationship between estrogen and PRL release exists in humans.

PMID- 11344581
TI  - Thyroid hormone action. Demonstration of similar receptors in isolated nuclei of
      rat liver and cultured GH1 cells.
AB  - High-affinity, limited-capacity nuclear binding activities, putative receptors
      for triiodothyronine, were detected after incubation of hormone with intact rat
      pituitary GH1 cells in culture, isolated GH1 cell nuclei, or rat liver nuclei.
      The total number of triiodothyronine binding sites per nucleus was similar in
      each case (approximately 8,000). The estimated equilibrium dissociation constants
      were virtually identical in isolated GH1 cell nuclei and rat liver nuclei, and
      both values were similar to that determined in intact GH2 cells. These results
      suggest that mechanisms of thyroid hormone action defined in cell culture could
      apply to thyroid hormone regulatory effects in vivo.

PMID- 11344582
TI  - The effect of vasopressin on phosphate transport in the proximal tubule of the
      dog.
AB  - Recollection micropuncture study was performed in 11 thyroparathyroidectomized
      dogs during antidiuresis to determine the effect of continuous vasopressin
      infusion at 50 mU/kg/h on proximal tubule phosphate and sodium transport. The
      animals were divided into two groups according to changes in mean arterial blood
      pressure. In the first group (five dogs) with increased blood pressure and
      glomerular filtration rate (GFR), mean proximal tubule fluid-to-plasma inulin
      ratio fell significantly from 1.69 to 1.53, whereas it remained unchanged at 1.60
      in the second group (six dogs) with no change in blood pressure. In contrast,
      mean proximal tubule fluid-to-plasma ultrafilterable phosphate ratio increased
      consistently in both groups, regardless of blood pressure changes. Since
      natriuresis as well as phosphaturia were observed in all animals, the sodium
      effect of vasopressin in the distal nephron must be mainly responsible for the
      natriuresis. It was concluded that vasopressin, when given in the doses employed,
      inhibits phosphate transport in the proximal tubule and sodium reabsorption in
      the distal nephron. An additional effect on proximal tubule sodium reabsorption
      appears to be related to the rise in blood pressure and GFR secondary to
      vasopressin administration.

PMID- 11344583
TI  - The role of superoxide anion radical in the reduction of ferritin iron by
      xanthine oxidase.
AB  - Superoxide dismutase exerted a pronounced inhibitory effect upon xanthine oxidase
      mediated reduction of iron in ferritin, ferric chloride, or ferric ADP. Maximal
      inhibition was observed when the superoxide dismutase concentration was only
      about 1% of that found in normal porcine liver. These observations indicate that
      superoxide anion radical is an intermediate in the reduction of iron by xanthine
      oxidase in vitro but not in vivo.

PMID- 11344584
TI  - Peri-marketing surveillance of lamotrigine in The Netherlands: doctors' and
      patients' viewpoints.
AB  - PURPOSE: Evaluation of daily clinical practice in prescribing lamotrigine in
      refractory epilepsy patients. METHODS: A collaborative, retrospective, peri
      marketing study was performed in in- and out-patients attending one of the three
      Dutch epilepsy centres. Analysis of both patients' and doctors' information was
      performed in 520 patients using questionnaires and medical files. RESULTS: After
      one year of treatment 76% of patients maintained LTG treatment, an intention-to
      treat analysis showed > = 50% seizure reduction in 23% of patients; 20-50%
      seizure reduction in 23% of patients. Six percent of patients became at least
      three months seizure free. In about 20% of patients seizures became less severe
      and shorter of duration, while in 6% an increase was found. After three months a
      significant decrease in number of concomitant antiepileptic drugs was found
      (change from mean 1.8 to 1.5 AEDs) (p = < 0.01). After twelve months the mean
      number of AEDs was 1.4 per patient. Overall percentage of side effects appeared
      to be significantly higher if patients' questionnaire data were used. Epilepsy
      patients considered side effects as an important factor in the choice of
      medication and in withdrawal of medication. Future developments of new AEDs
      should take this into account. CONCLUSION: This perimarketing study gives insight
      information about long-term daily use of lamotrigine, with emphasis on
      effectiveness. Patients complained in the questionnaires much more about side
      effects, than was known according to the medical file. Therefore, it seems
      necessary to perform perimarketing studies more systematically.

PMID- 11344585
TI  - The role of the community pharmacist in drug abuse: a comparison of service
      provision between Northern Ireland and England/Wales.
AB  - AIM: The aim of the present research was to establish the current extent of
      pharmacists' contact with illicit drug users in Northern Ireland, their
      willingness to provide services for this group and to compare the findings with
      data from a 1995 national survey of community pharmacies in England and Wales.
      METHOD: The questionnaire developed by the National Addiction Centre for research
      in England/Wales was used to collect data. It was mailed on two occasions (March
      and April 1999) together with a covering letter and a prepaid return envelope to
      all community pharmacies in Northern Ireland (n = 507). A final reminder letter
      was included in the local wholesalers' medical delivery for the attention of the
      pharmacist in May 1999. MAIN OUTCOME MEASURE: The extent to which Northern
      Ireland pharmacists had contact with and provided services to illicit drug users
      compared to pharmacists in England/Wales. RESULTS: A response rate of 67.5% was
      achieved. Respondents in Northern Ireland were providing fewer services to drug
      users than those in England/Wales. Respondents reported dispensing methadone for
      the treatment of addiction/misuse to only 9 patients, while only 17 pharmacists
      had been asked to sell injecting equipment in the previous week and no pharmacist
      was participating in a needle exchange scheme. However, most respondents
      indicated their willingness to provide such services. Barriers towards the
      provision of services were, however, highlighted e.g. the need for training and
      the establishment of support systems. CONCLUSION: Pharmacists in Northern Ireland
      are in a position to contribute to the policy agenda in Northern Ireland for drug
      misuse, prevention, treatment and harm minimisation--roles which the survey
      indicates they are willing to embrace. However, training programmes, support
      systems and adequate remuneration packages must be established before they will
      be in a position to participate fully.

PMID- 11344586
TI  - Pharmacotherapeutic options in inflammatory bowel disease: an update.
AB  - Chronic inflammatory bowel disease (IBD) refers to two diseases: Crohn's disease
      (CD) and ulcerative colitis (UC). The etiology of IBD remains unknown. The
      understanding of the pathogenesis has expanded greatly over the last decade. The
      combination of genetic risk factors, abnormalities in the immune system, vascular
      and neural factors, and random environmental factors may all play an important
      role. Most treatments currently in use have multiple action. The choice of
      appropriate medical treatment is determined by the status (inductive or
      maintenance therapy) and severity of the disease and the potential for toxicity.
      Despite the variety of medical therapies available for the treatment of IBD, none
      is ideal. Ongoing research into the well-established drugs, as well as novel
      agents with more precise targets, may contribute to an optimal therapy of IBD in
      the near future. In this paper the current (5-aminosalicylates,
      glucocorticosteroids, thioguanine derivatives, methotrexate, cyclosporin and
      infliximab) as well as some of the new (mycophenolate mofetil and thalidomide)
      therapeutic options are reviewed.

PMID- 11344587
TI  - "No thank you": why elderly patients declined to participate in a research study.
AB  - OBJECTIVES: To compare the population consenting for a study of the effectiveness
      of a pharmacist-run medication review clinic with the population not consenting
      for patients aged over 65 years old with respect to age, sex and number of repeat
      medicines. To explore the reasons why some patients declined to consent to the
      study. METHODS: Letters were sent to 2,403 patients aged 65 and over and taking
      at least one repeat medicine from 4 general practices. If no reply was received
      to a second letter they were followed up by telephone. If they declined to
      consent they were asked for their reasons. Data for consenting and non-consenting
      patients was collected on the stratification factors: age, sex and number of
      repeat medicines. Multiple logistic regression was used to assess the association
      of each factor with consent rates. RESULTS: Consenting patients were dissimilar
      to non-consenting patients. Patients were less likely to consent if they were
      older, OR (95% CI) = 0.54 (0.46, 0.64), or female, OR (95% CI) = 0.74 (0.63,
      0.88). Patients were more likely to consent if on 5 or more repeat medicines: OR
      (95% CI) = 1.3 (1.1, 1.5). Ten broad categories of reasons why patients did not
      wish to participate were identified from the patient interviews. CONCLUSIONS:
      Patients were less likely to give their consent if they were elderly, female and
      on fewer repeat medicines. A number of administrative and behavioural factors
      were identified which reduced the chances of informed consent being given. These
      factors need to be addressed to maximise numbers of consenting patients in
      medication review studies.

PMID- 11344588
TI  - Comparative trials in registration files of cardiovascular drugs: comparator
      drugs and dosing schemes.
AB  - Registration files of 13 cardiovascular drugs were analysed with respect to the
      number of double-blind phase-III clinical trials, the use of placebo and active
      comparator drugs and their dosing schemes. Half of the 146 double-blind trials
      used active comparator drugs. The majority of files included first-choice
      reference drugs, but we also found trials in three files with lower dosing
      schemes of comparator drugs and four files which included only placebo or active
      controlled double-blind trials. To allow a better interpretation of the
      information provided in European Public Assessment Reports, which are published
      for every product approved for marketing in the European Union, uniform reporting
      is recommended on basic details of trial design, such as comparator drugs used
      and dosing schemes.

PMID- 11344589
TI  - Pharmacist involvement with warfarin dosing for inpatients.
AB  - This study audits the quality of medical inpatient maintenance anticoagulation
      control by junior doctors and evaluates the impact of the implementation of
      warfarin guidelines on the anticoagulation control achieved by doctors compared
      with that by a pharmacist. Introduction of warfarin guidelines made no
      significant difference to the anticoagulation control achieved by junior doctors.
      The pharmacist demonstrated significantly better (p < 0.001) therapeutic control
      than the doctors in the areas of anticoagulation control measured, namely
      international Normalised Ratios (INRs) less than two and greater than six and
      INRs within the therapeutic range. The pharmacist overall, maintained 58% of INRs
      within range compared to 15% by junior doctors, over a twelve week period. In
      addition, there was a major reduction in the number of INRs requested by the
      pharmacist. Extrapolated over a year, this would amount to approximately 3,500
      fewer INR requests on the medical wards. The effect of pharmacist dosing was also
      demonstrated in the difference in timing of warfarin administration by nursing
      staff. A much larger percentage of doses (90%) was administered within one hour
      of the prescribed time, compared to junior doctors (15%). This study has
      demonstrated that there is a role for the clinical pharmacist dosing warfarin for
      inpatients, by offering improved anticoagulation control, in addition to the
      accepted role in outpatients. It also shows that such involvement provides
      improved quality of patient care, reduced number of INR requests and improvement
      in the coordination of patient discharge between primary and secondary care.

PMID- 11344590
TI  - Neuropsychiatric symptoms during cefepime treatment.

PMID- 11344591
TI  - The perceived role and skills of pharmacists in asthma management after in-house
      training.
AB  - OBJECTIVE: To evaluate perceived roles and skills of pharmacists in asthma
      management before and after a training intervention that consisted of six in
      house training sessions. METHOD: Altogether 315 pharmacists in the intervention
      group and 121 pharmacists in the control group participated in the study. The
      data on study variables were collected by a questionnaire during the first and
      last training sessions. MAIN OUTCOME MEASURES: Pharmacists' perceptions of their
      role, perceived skills, estimates of patients receiving counselling and
      experienced problems. RESULTS: Based on their ratings for 16 topics, the
      pharmacists' perceptions about their role in counselling asthma patients remained
      rather stable. Handling of the inhalers and inhalation technique were considered
      as the most important aspects of counselling and issues dealing with the disease
      were regarded as the least important. Using a self-rated scale (4-10 scale),
      pharmacists' perceived counselling skills improved in the intervention group (6.5
      vs 7.6), but not in the control group (6.5 vs 6.4). In the intervention group,
      the pharmacists' estimates of the proportion of new users of asthma medicines
      receiving counselling increased from 48% to 61% and that of old users from 18% to
      26%. Before the training, the most commonly experienced problem in counselling
      was the pharmacists' lack of knowledge and skills. After the training,
      pharmacists experienced problems mainly with communication. CONCLUSION: When
      pharmacists are included in the support system for any patients group, their
      capabilities of fulfilling their role have to be assessed. In particular,
      communication skills and outcome-oriented counselling require attention.

PMID- 11344592
TI  - Non-specific nature of specific language impairment: a review of the literature
      with regard to concomitant motor impairments.
AB  - In the light of emerging suggestions that language and motor deficits may co
      occur, the literature on specific language impairment (SLI) was reviewed to
      investigate the prevalence of co-morbidity between SLI and poor limb motor skill
      in children diagnosed with language impairments. An extensive literature search
      was undertaken and the subsequent findings evaluated with particular reference to
      issues surrounding symptom co-occurrence, as well as to theoretical and
      aetiological accounts of SLI. Clearly substantial co-morbidity exists between SLI
      and poor motor skill, suggesting that SLI is not a specific disorder of language,
      but rather that children with SLI experience a broader range of difficulties, of
      which motor incoordination is one. Current theoretical explanations of SLI do not
      account fully for such wide-ranging difficulties and it may be useful in the
      future to focus on a more detailed explanation in terms of shared cognitive
      processes or neuromaturational delay to understand further the nature of the
      disorder, to explain it theoretically and to deal with it practically.

PMID- 11344593
TI  - Educational attainments of school leavers with a preschool history of speech
      language impairments.
AB  - This paper reports a follow-up study of a cohort of 16- and 17-year-olds with a
      preschool history of speech-language impairment and whom Bishop and Edmundson
      (1987) originally studied. Information collected by questionnaire showed that the
      GCSE grades of those whose language impairments had resolved by 5;06 were below
      those of age-matched controls. However, the number of GCSE examinations entered
      and passed was significantly more than those of the 'persistent S-LI' and
      'general delay' groups. Overall, IQ was the strongest predictor of educational
      attainment. However, even when IQ was controlled, literacy skills accounted for
      independent variance in achievement, especially among those with a history of
      language difficulty. The survey also noted that the majority of students across
      all groups remained in full-time education; however, the adolescents with a
      background of S-LI were more likely to follow vocational and employment training
      courses rather than A-levels.

PMID- 11344595
TI  - Follow-up of children attending infant language units: outcomes at 11 years of
      age.
AB  - A large cohort of 242 children who had been attending infants language units at 7
      years of age was followed up when the children were in their final year of
      primary school. Two hundred (83%) of the children were reassessed at 11 years of
      age on a wide battery of language and literacy measures, on a test of non-verbal
      ability, an autism checklist and a communication checklist. In total, 89% of
      children still scored < 1 SD from the mean on at least one test of language and
      the majority (63%) scored poorly on three or more assessments demonstrating
      widespread difficulties. Compared with non-verbal abilities at 7 years of age, a
      large proportion of the cohort also performed poorly on performance IQ subtests
      (28%). A further 10 children scored highly on a checklist for autistic spectrum
      disorder. Thus, only 115 (58%) children could be said to meet criteria for
      specific language impairment. A small group of 16 children appeared to have
      entirely resolved their difficulties. These outcomes and their implications for
      education and long-term impact of the disorder are discussed.

PMID- 11344594
TI  - Relationship between parenting behaviours and specific language impairment in
      children.
AB  - This study investigated the relationship between parenting behaviours and
      specific language impairment (SLI) in children. Using a case-control design, data
      on 177 kindergarten children with SLI and 925 kindergarten children who were
      typically developing were collected using a parental questionnaire. Parents were
      interviewed about parenting practices classified into the following categories:
      conversing with children, teaching behaviours, the child's daily routine and
      discipline. The results revealed that parents of children who were normally
      developing had engaged their children in particular conversational activities
      more frequently than had parents with children with SLI. Parents of children
      diagnosed with SLI tended to teach their children school readiness skills (the
      alphabet and colours) and discipline their children more frequently. These
      relationships continued to hold after controlling for maternal education and
      family economic need with the exception of teaching children colour names. The
      results suggested that additional investigations that examine the association
      between these parental behaviours and children's language status through direct
      observation are warranted.

PMID- 11344596
TI  - High-frequency verbs and verb diversity in the spontaneous speech of school-age
      children with specific language impairment.
AB  - Low verb diversity and heavy reliance on a small set of high-frequency 'general
      all purpose (GAP)' verbs have been reported to characterize specific language
      impairment (SLI) in preschool children. However, discrepancies exist about the
      severity of this deficit, particularly in whether these children's verb diversity
      is commensurate with their MLU level and whether verb diversity is more severely
      affected than general lexical diversity. Conflicting findings have been reported
      regarding the use of GAP verbs. This relatively large (n = 100) study extended
      the investigation of lexical diversity and high-frequency verb use to school-age
      children with SLI and NL peers and examined a particular hypothesis concerning
      the role of high-frequency verbs in language development. No differences were
      found between groups in general lexical diversity or verb diversity in samples of
      a set number of tokens. The results did not suggest that verb diversity
      constitutes an area of specific deficit in spontaneous production for children
      with SLI. SLI and NL groups were indistinguishable in high-frequency verb use.
      Extensive use of high-frequency verbs by both groups indicates that their use is
      part of normal development. Results are reported that support the hypothesis that
      high-frequency verbs act as prototypes for major meaning categories, permitting
      semantic and syntactic simplification with minimal losses in information value.

PMID- 11344597
TI  - Communication deficits: assessment of subjects with frontal lobe damage in an
      interview setting.
AB  - This paper is about communication deficits in an interview setting among
      adolescents with frontal lobe damage. One of the predominant characteristics of
      these patients is difficulty taking the context into account. Pragmatic theories,
      which attempt to clarify the link between the formal structure of language and
      the extra-linguistic context (such as the interlocutor's characteristics or
      strategies), may help provide insight into the difficulties of these patients. An
      interview setting, viewed here as a communication situation, is governed by an
      interaction format based on specific cooperative principles. In this study, the
      results of subjects with frontal lobe damage (in the role of interviewee) were
      first compared with those of normal subjects in an interview situation. Three
      pragmatic indexes were considered: the number of utterances per speaking turn
      (speech quantity), amount of digression (keeping to the topic or predefined
      subject of conversation shared by the interlocutors) and prevalence of within
      subject contingency speaking turns without an intervening remark by the
      interviewer (topic development). Secondly, we attempted to determine whether the
      patients' discourse was dependent upon the interviewer's conversational strategy
      (structured, non-structured, or alternating). The results clearly point out the
      extent of the difficulty frontal lobe patients have conforming to the rules of
      the interview situation, whether regarding the amount of speech they produce or
      their ability to keep within and/or development of the topic of conversation. The
      data also indicated that the patients' linguistic productions varied with the
      interviewer's strategy. The structured strategy did not always give rise to the
      best performance: while the unstructured and alternating strategies allowed
      patients to produce more utterances per speaking turn, the alternating strategy
      enabled better development of the interview topic. These results suggest that
      such variations could be put to fruitful use in remedial techniques.

PMID- 11344598
TI  - Re: Phonological awareness therapy and articulatory training approaches.

PMID- 11344599
TI  - Role of HPV-assay as an adjuvant to Pap's smear for diagnosis of carcinoma
      cervix.

PMID- 11344600
TI  - Microwave technique in histopathology and its comparison with the conventional
      technique.
AB  - 125 formalin fixed human tissues from different organs and 50 fresh animal
      tissues were taken. Each tissue piece was divided into two. Fresh animal tissues
      were fixed and processed in a domestic microwave oven and formalin fixed tissue
      were only processed in microwave oven. Simultaneous conventional processing was
      also carried out. Among the fresh tissues, 34 pieces were fixed in 10% formalin
      and 16 were stabilized in normal saline, with microwave irradiation. For
      histoprocessing graded ethanol (70% and absolute) for 150 tissues and graded
      isopropanol (70% and absolute) for 25 tissues were used for dehydration in
      microwave technique. Chloroform for 95 tissues, xylene for 15 tissues and
      isopropanol for 65 tissues were used as clearing agent in microwave technique.
      Liquid paraffin was impregnating agent in all 175 cases. The oven was operated at
      50% power for 10 cases and 40% power for 165 cases. Recording of temperature
      could not be done. Regarding fixation with formalin 80% cases gave satisfactory
      result, while with normal saline, only 30% cases were satisfactory. Regarding
      dehydration with ethanol 80% were satisfactory and with isopropanol 60% were
      satisfactory. Regarding clearing--both chloroform and isopropyl alcohol gave
      satisfactory results in 80% cases but with, xylene tissues were fragmented and
      brittle.

PMID- 11344601
TI  - Polymerase chain reaction using IS6110 primer to detect Mycobacterium
      tuberculosis in clinical samples.
AB  - Nucleic acid amplification using IS6110 primers to detect Mycobacterium
      tuberculosis in clinical specimens has been extensively used as laboratory tool
      for the diagnosis for tuberculosis. Despite it's dramatic scientific value in
      practice, it is not as sensitive as expected for the detection of Mycobacterium
      tuberculosis. The results of the study suggest that PCR using 123 bp fragment of
      DNA belonging to IS6110 is specific (95.6%) but only has a sensitivity of 30% to
      detect M. tuberculosis in clinical specimens.

PMID- 11344602
TI  - Primary malignant giant cell tumour of bone--a study of two cases with short
      review.
AB  - Primary malignant giant cell tumour of bone is extremely rare. It is distinctly
      separate from benign metastasising giant cell tumour of bone and secondary
      malignant giant cell tumour which occurs in response to radiotherapy and repeated
      curettage of benign giant cell tumor. The tumor has high mortality rate. It
      usually affects lower end of femur and upper end of tibia. Two usually affects
      lower end of femur and upper end of tibia. Two cases, on involving upper end of
      tibia and other in vertebra are discussed. Extreme paucity of literature prompted
      to publish this article. A short review of radiological appearance,
      histopathological findings and treatment modalities is highlighted.

PMID- 11344603
TI  - Electron microscopy of buffalo green monkey kidney cells persistently infected
      with hepatitis A virus and immunolocalization of HAV antigens.
AB  - Studies were carried out to analyse the ultrastructural changes and the
      distribution of hepatitis A virus (HAV)/antigens at subcellular level in buffalo
      green monkey kidney (BGMK) cells persistently infected with HM-175 strain of HAV.
      HAV infected BGMK cells showed distinct abnormalities in the endoplasmic
      reticulum and cytoplasmic membrane as compared to uninfected cells. The
      abnormalities were characterized by wavy arrays, structures like myelin, annulate
      lamellae, cytoplasmic inclusion bodies and vesicles. The wavy arrays within the
      cytoplasm of the host cells appeared to represent degenerating membranes. A
      complex myelin like body was found in close association with a group of virus
      like particles. Annulate lamellae like structures involving single paired
      membrane were detected infrequently whereas the cytoplasmic vesicles were
      numerous in these cells. An indirect immunogold technique was utilized to
      localize the HAV antigenin infected cells. A high density immunogold label for
      HIV like particles was predominantly detected in cytoplasmic vesicles. These
      results suggest a strong association of membrane substructure in vesicle forms
      with the compartmentalized replication of HAV within persistently infected host
      cells.

PMID- 11344604
TI  - Efficacy of a modified Ultra Fast Papanicolaou (UFP) stain for breast aspirates.
AB  - The chief limitation of Ultra Fast Papanicolaou (UFP) stain, suggested by Yang
      and Alvarez (1995), is that, Richard Allan Haematoxylin (RA-H) and Richard Allan
      Cytostain (RA-C), used in the staining procedure are not universally available.
      It has not been established so far, whether, changes in the reagents and their
      proportions depending on the local availability, influence the performance of the
      stain. The objective of this study was to assess the feasibility and
      applicability of a modified UFP stain to suit our local laboratory supplies of
      chemical dyes, as applied to the permanent smears prepared from Fine Needle
      Aspiration (FNA) of breast lumps. In the present study, smears from FNA from 100
      breast lumps were stained by the modified UFP stain. The modification consisted
      of following two changes: use of Gill's Haematoxylin instead of RAH and omission
      of Orange G from cytostain. Eighty Six breast aspirates were adequate for
      interpretation. Smears showed transparent cells with crisp nuclear features,
      equal to and even better than the conventional Papanicolaou stain, in a blood
      free background. There was an increase in total staining time by 40 seconds. We
      recommend the use of this modified UFP stain, only if similar reagents are being
      used in other laboratories. Otherwise situation specific modifications may be
      needed. If the UFP stain is to be used for tissues where the chances of
      cytoplasmic keratinization are negligible, then the use of Orange G component of
      the stain may become redundant.

PMID- 11344605
TI  - Studies on blood factors responsible for rise in ESR.
AB  - Rise in ESR following inflammation processes is well known. However, the exact
      factors in blood responsible for the rise remain largely unknown. The present
      experimental work on mixing of plasma from pulmonary tuberculosis cases with RBCs
      from healthy volunteers indicates that ESR rising properties reside in plasma and
      not in RBCs. Levels of C-reactive proteins (CRP) are also known to rise following
      inflammation and hence CRP could contribute to rise in ESR. However, absorption
      of C-reactive protein from the plasma does not reduce the ESR and suggests that C
      reactive proteins are not directly involved in raising ESR. Further experimental
      work was carried out to see whether cytokines released by mononuclear cells are
      responsible. However, cell culture supernatants added to whole blood samples did
      not cause rise in ESR. The ESR rising substances in plasma were non-dialysable
      and thus were of larger molecular weight.

PMID- 11344606
TI  - Identification of yeasts from clinical specimens by oxidase test.
AB  - A total of 100 yeasts and yeast like fungi isolates from clinical specimens were
      negative for oxidase production on Sabouraud dextrose agar. When grown on
      Columbia agar, chocolate agar, tryptose agar, Mueller-Hinton agar, brain heart
      infusion and a medium resembling Sabouraud's dextrose agar but with starch
      instead of dextrose, all the isolate of Candida albicans (55), C. guilliermondii
      (6), C. parapsilosis (14), C. tropicalis (6), C. pseudotropicalis (6) and
      Crytococcus neoformans (2) were positive for oxidase producation. Torulopsis
      glabrata (2), Saccharomyces cervisiae (2) and two out of seven isolates of C.
      krusei were negative for oxidase test.

PMID- 11344607
TI  - Prevalence of enterically transmitted hepatitis viruses in patients attending a
      tertiary--care hospital in south India.
AB  - The prevalance of enterically transmitted hepatitis viruses, namely, hepatitis A
      virus (HAV) and hepatitis E virus (HEV) were studied in 404 patients with acute
      hepatitis attending a tertiary-care hospital in south India. Presence of current
      HAV/HEV infection was ascertained by the demonstration of IgM antibodies. In 381
      patients tested for both agents, HAV IgM was present in 51(13.3%) and HEV IgM
      present in 66(17.3%). There was dual infection in 3 males (0.8%). HEV infection
      was seen mostly in older children and adults with only 5.5% occurring in children
      < 12 years of age. HAV infection was commonly seen to occur in < 12 years of age
      group (52.7%). One hundred and twenty-six patients were from the Vellore region,
      among whom HAV and/or HEV aetiology was observed in 28.5%. In this region there
      did not appear to be any correlation between occurrence of acute hepatitis due to
      these viruses and rainfall or environmental temperature. Acute hepatitis due to
      enteric hepatitis viruses was seen throughout the year.

PMID- 11344608
TI  - Evaluation of tumour markers in carcinoma breast.

PMID- 11344609
TI  - Immunohistochemical localization of transferrin in human breast cancer tissue.
AB  - The present study was planned to detect the iron binding protein, transferrin
      (TR) in paraffin sections of the human breast tumors. The distribution of
      transferrin has been studied in 153 cases (63 benign lesions and 90 malignant
      tumors). The extent of staining reaction was determined by semiquantitative
      grading (weak, moderate and consistent). Positivity rate for transferrin was
      higher (92.2%) in malignant tumors as compared to benign breast lesions (28.5%)
      with significant p value (p = 0.0001) for both the groups. The intensity was
      variable in both the groups, being more intense in the malignant tumors. Tumors
      with higher grade of malignancy presented consistent positive staining along with
      the lymph nodes involved. The extent of immunoreactivity revealed a significant
      positive correlation with axillary lymph node status. However, no significant
      correlation was found with the age of the patients. Thus the study of transferrin
      in breast tumors besides being of prognostic significance helps in the further
      management of malignant lesions of the breast.

PMID- 11344610
TI  - Lymphangiectatic fibrolipomatous polyp of the palatine tonsil.
AB  - A rare benign polypoid tumor of the right palatine tonsil is described in a 23
      year old male. It contained dilated lymphatic channels surrounded by fibrous
      tissue and foci of mature fat. The features of this lesion add support to the
      hypothesis that benign tumors of tonsil may be hamartomas of tonsil rather than
      true neoplasms. The differential diagnosis of polypoid lesions of the tonsil is
      discussed.

PMID- 11344611
TI  - Annuloaortic ectasia: a case report.
AB  - Annuloaortic ectasia (AAE), in which there is an idiopathic aortic root dilation
      leading to pure aortic regurgitaion (AR), is a rare disorder and is usually seen
      as a forme--fruste of Marfan's syndrome. We report a case in which the patient
      presented with rapid onset of symptoms of heart failure and was being treated for
      mitral regurgitation due to dilated cardiomyopathy. Postmortem findings revealed
      an enlarged heart with annuloaortic ectasia.

PMID- 11344612
TI  - Lipoleiomyoma of broad ligament: a case report.
AB  - Lipoleiomyoma is a very uncommon tumor, and broad ligament of uterus is one of
      the rare sites. No case has been reported in last five years. This case is
      presented because of its rarity and its uncommon site of occurrence.

PMID- 11344613
TI  - Ovarian strumal carcinoid--report of a case that matastasized.
AB  - Ovarian teratomas are known for their ability to form a wide variety of tissues.
      One unusual example of this potential is the strumal carcinoid in which the
      thyroid tissue is found in intimate association with carcinoid tumor. Although
      considered as a malignant transformation of struma ovarii, it is almost always
      benign. We report a rare case of strumal carcionid in a 44 year old lady who had
      metastasis in the contralateral ovary, myometrium and lungs.

PMID- 11344614
TI  - Ectopic ovarian pregnancy--a case report.
AB  - Ectopic pregnancy is an increasingly important health problem. We report a rare
      ovarian ectopic pregnancy which was diagnosed clinically and confirmed
      pathologically.

PMID- 11344615
TI  - A unique case of metastatic penile basal cell carcinoma.
AB  - Basal cell carcinoma rarely arises in the penis and metastasizes infrequently.
      This article presents probably the first case report of a metastatic penile basal
      cell carcinoma.

PMID- 11344616
TI  - Leiomyosarcoma of the mesocolon--a case report.
AB  - Retroperitoneal leiomyosarcomas including those arising from the mesentery are
      rare. These account for 5.8% of all soft tissue sarcomas. Most of these tumors
      present in late life with female preponderance. Diagnosing these tumors at an
      early stage is difficult due to their location. Hence, most of them attain large
      sizes with metastases to distant sites at the time of diagnosis. We report a case
      of leiomyosarcoma arising from the sigmoid mesocolon due to it's rarity and
      unusual clinical presentation.

PMID- 11344617
TI  - Primary choriocarcinoma of stomach.
AB  - A 45 year old patient wad admitted with pain abdomen and a palpable mass in the
      epigastrium of 3 months duration. Endoscopy revealed growth in the stomach and
      biopsy showed poorly differentiated Carcinoma. Distal radical subtotal
      gastrectomy was done. Histopathology revealed choriacarcinoma with
      Syncytiotrophoblastic and cytotrophoblastic and foci of adenocarcinoma.
      Postoperatively urine and serum had very high levels of beta-human chorionic
      gonogotrophins (B-HCG). Immunochemistry showed positivity for B-HCG. Clinically
      and on scan both the testis were normal. Because of its rarity, we are presenting
      this case with brief review of literature.

PMID- 11344618
TI  - Granulocytic sarcoma of humerus, an unusual association of acute myeloblastic
      leukemia--a case report.
AB  - Ganulocytic sarcoma (Chloroma) is a tumour of rare variety usually in
      assocoiation with granulocytic leukemia. It is related to soft tissue with
      extramedullay infiltration. We present a case of granulocytic sarcoma of humerus
      which preceded the initial clinical manifestation of acute myeloid leukemia in a
      young patient which ultimately proved to be FABM2 variety. Though many tissues
      are affected by this tumour but the most favoured site is the bone.

PMID- 11344619
TI  - Malignant peritoneal mesothelioma deciduoid or anaplastic variant? A point to
      ponder.
AB  - A case of peritoneal meosthelioma displaying unusual morphology, occurring in a
      53 years old woman is described. The role of immunohistochemistry and electron
      microscopy in the evaluation of this tumour is stressed. The appropriate
      terminology to be used and possible etiologic factor are also discussed.

PMID- 11344620
TI  - Acute lymphoblastic leukaemia with giant intracytoplasmic inclusions--a case
      report.
AB  - Acute Lymphoblastic Leukaemia (ALL) with intracytoplasmic inclusions is a rare
      and unusual subtype of acute leukaemia. Here we describe a case of ALL with
      intracytoplasmic inclusions in an adult female. These inclusions stained negative
      for Myeloperoxidase (MPO), Sudan Black E (SBB) and alpha-naphthyl acetate
      estarase (ANAE) and positive for Periodic Acid Schiff (PAS). This case is being
      presented for its unusual occurrence and to recognise the characteristics of this
      subtype of ALL to avoid a misdiagnosis of AML.

PMID- 11344621
TI  - Primary orbital NHL--a rare entity, diagnosed on FNAC.
AB  - Primary Orbital NHL is a rare, malignant neoplasm of the orbit. FNAC is
      particularly useful for patients with such non-resectable, deep seated
      retroorbital tumors which are difficult to biopsy and in whom a firm cytologic
      diagnosis is vital to guide further treatment, such as radiotherapy and
      chemotherapy. A case of 70 years old female is described in the present article.

PMID- 11344622
TI  - Filariasis as a cause of pleural effusion.
AB  - Filariasis, a mosquito borne disease is endemic in many tropical countries and
      sub tropics including India. A 44 years old male presented with signs and
      symptoms of pleural effusion. Pleural fluid on examination was exdudative in
      nature and showed presence of microfilariae of Wuchereria bancrofti.

PMID- 11344623
TI  - Report of NEQAP--the ten years growth success.
AB  - External quality assessment forms a vital aspect of health laboratory service.
      Decisionto start National External quality assessment Programme (NEQAP) under
      IAPM was taken at the Annual conference at Bombay in December, 1989 to be run
      from Varanasi at the initiative of the author. It has been running now for more
      than ten years and is unique in that it does not have financial backing from
      government or any institution and runs by contributions from participants and
      help from IAPM from time to time. Another unique feature is that it is truly
      multiparametric including clinical chemistry, hematology, microbiology and
      cytology. It covers about 300 labs from all corners of India. Details of the IAPM
      NEQAP programme made during successful running for ten years (1990-1999) and
      recommendations for further action are given.

PMID- 11344624
TI  - [Treatment of erosive gastropathy caused by nonsteroidal anti-inflammatory agents
      using low doses of antacids].
AB  - In an open clinical, endoscopy controlled study involving 31 patients with
      erosive NSAIDs-induced gastropathy without Helicobacter pylori infection, the
      effect of low dose of antacids (120 mmol/l) with aluminium oxide and magnesium
      oxide (Maalox) administered for 4 weeks was followed. The administration of
      NSAIDs was not interrupted during the time of treatment. Healing rate of the
      gastric erosions after four weeks reached 65% (20/31) and endoscopic score in the
      gastric mucosa proved significant improvement (0.97 +/- 0.49 compared to 0.07 +/-
      0.25, p < 0.01). Our results suggest efficacy of low dose antacids containing
      aluminium in the treatment of NSAIDs-induced gastric erosions.

PMID- 11344625
TI  - [Monitoring phagocyte activity and free radicals in Helicobacter pylori
      infections].
AB  - The presence of infection in organism induces a lot of Immunological reactions
      accompanied by creating free Radicals and reactive oxygen species (ROS). These
      play an important role in elimination of bacteria but also in tissue injury in
      surrounding. The aim of presented study was to focus on monitoring of ROS and
      phagocyte activation in subjects infected by Helicobacter pylori (HP) and thus to
      contribute to our knowledge of the etiopathogenic role of HP in inflammatory
      gastrointestinal diseases. The results report some differences, which
      interpretation opens a lot of questions showing how important of role ROS in HP
      infection may play.

PMID- 11344626
TI  - [Cross-sectional study of choice of drug therapy in the acute phase of treatment
      in acute myocardial infarct--part 1].
AB  - INTRODUCTION: Treatment of acute myocardial infarction is undergoing changes. In
      the treatment of acute myocardial infarction in particular the following proved
      useful: thrombolysis, administration of anti-aggregating drugs, beta-blockers and
      inhibitors of angiotensin converting enzyme. An decisive part is played by the
      interval between the onset of symptoms and the beginning of hospital treatment.
      OBJECTIVE: To describe treatment of patients hospitalized at intensive care units
      for acute myocardial infarctions. Investigate differences between faculty and
      other hospitals. METHOD: The authors investigated by means of questionaires in a
      prospective study during the first three months in 1996 all patients who were
      hospitalized on account of acute myocardial infarction. The investigation was
      implemented in seven intensive care units of faculty hospitals and in nine
      intensive care units of hospitals and information on diagnosis, pharmacotherapy
      and results of therapy were assembled. During the first 24 hours of treatment
      more detailed information was procured. RESULTS: Antiaggregants were used in 88%,
      nitrates in 77.8%, thrombolytics, beta-blockers and and ACE inhibitors in ca 30%
      patients. Percutaneous transluminal coronary angioplasty was used in ca 7%
      patients. CONCLUSIONS: The authors describe treatment of the acute stage of
      myocardial infarction. In faculty hospitals in 1996 thrombolysis, percutaneous
      transluminal coronary angioplasty, beta-blockers and nitrates by the i.v. route
      were used more frequently.

PMID- 11344627
TI  - [Effect of alendronate therapy on bone turnover--results of a multicenter study].
AB  - Sodium alendronate is a bisphosphonate of the IInd generation with a strong
      antiresorptive effect. Its favourable effect on reduction of the incidence of
      vertebral and non-vertebral fractures was repeatedly confirmed. The objective of
      the multicentre study was to evaluate the effect of administration of 10 mg of
      sodium alendronate combined with 1000 mg of elemental calcium administered in the
      course of three months on the N-terminal telopeptide(NTx) a sensitive marker of
      bone resorption. The group comprised 275 postmenopausal women with
      densitometrically confirmed osteoporosis. After three months treatment a 53%
      decline of NTx values occurred as compared with baseline values. This finding
      confirms the favourable effect of sodium alendronate on bone remodelling. A
      decline of the concentration of bone markers is one of the good predictors of the
      effectiveness of treatment focused on reduction of atraumatic osteoporotic
      fractures.

PMID- 11344628
TI  - [Serum copper levels in patients with acute and chronic types of ischemic heart
      disease and its relation to lipoprotein levels and extent of coronary
      atherosclerosis].
AB  - The authors assessed serum copper and lipoprotein concentrations in a group of 67
      patients hospitalized successively at the cardiological department. During
      hospitalization they were subjected to selective coronarography with assessment
      of the angiographic score. In 35 patients the angiographic examination was made
      during the chronic stage of IHD (group A), in 32 patients it was indicated on
      account of acute coronary syndrome (group B). The authors found that serum copper
      concentrations are significantly higher in patients with acute forms of IHD
      (group B, p < 0.001). Serum copper concentrations do not correlate significantly
      with lipoprotein concentrations nor with the extent of coronary atheroclerosis
      (angiographic score).

PMID- 11344629
TI  - [Monitoring minimal residual disease in patients with hairy cell leukemia in
      complete remission after treatment with 2-chlorodioxyadenosine].
AB  - Treatment of hairy cell leukemia with 2-chlorodeoxyadenosine (2-CdA) induces in
      85% patients complete remission. Complete remission is defined as the condition
      when signs of activity of the disease are absent, splenomegaly and
      lymphadenopathy are absent, the hemoglobin concentration is > or = 120 g/l, the
      absolute number of granulocytes is > or = 1.5 x 10(9)/l and the number of
      thrombocytes is > or = 100 x 10(9)/l. In complete remission in the peripheral
      blood, bone marrow aspirate and bioptic samples obtained by trephin bone marrow
      core biopsy, using standard staining (hematoxylin-eosin and May-Grunwald-Giemsa's
      method), no leukemic cells are present. When more sensitive methods are used
      (immunophenotyping, immunohistochemistry or molecular genetic methods), a
      persisting leukemic population can be detected which is described as minimal
      residual disease (MRD). For detection of MRD the authors used immunohistochemical
      examination of bone marrow with DBA.44 antibodies. As leukemic cells they
      described those which produced intense cytoplasmic and membrane positivity with
      antibody DBA.44 and corresponded morphologically to hairy cells. For evaluation
      computer analysis of the picture LUCIA-M was used. The infiltration grade was
      examined on three areas of standard size (3 x 65,265 micron 2) and expressed in
      percent. A total of 45 trepanobioptic specimens from 21 patients were examined
      who achieved after treatment with 2-CdA complete remission. In all samples
      suitable for evaluation the presence of leukemic cells (MRD) was detected with a
      median of 3% and a range of 1% to 18%. With induction of complete remission
      correlates also the low serum level of the soluble receptor for IL-2 (sIL-2R). In
      a female patient after 24 months of treatment with 2-CdA the grade of leukemic
      infiltration rose from 1% to 12% and during the 36th month to 50% DBA.44+
      leukemic cells. The incipient relapse in this patient was not associated, despite
      marked infiltration of bone marrow, with failure of hematopoiesis and a marked
      rise of sIL-2R.

PMID- 11344630
TI  - [Endoscopic sonography in the diagnosis of chronic pancreatitis in the early
      stage].
AB  - The author summarizes in the submitted review diagnostic possibilities of early
      stages of chronic pancreatitis. He evaluates from that aspect possibilities of
      common imaging methods (ultrasonography, computer tomography, endoscopic
      retrograde cholangiopancreatography) and endoscopic ultrasonography (EUS).
      Evaluation of the secretory exocrine capacity by means of the secretin-cerulein
      test. Although the method is demanding from the aspect of routine diagnosis, it
      is a method with comparable sensitivity and perhaps even greater specificity than
      ERCP. Other tests of exocrine pancreatic secretion are not sufficiently sensitive
      to be used for this diagnosis. Among imaging methods ERCP which is still
      considered the gold standard, evaluates even subtle changes in the efferent
      system. Endoscopic ultrasonography visualizes rather discrete changes of the
      parenchymatous structure, areas of fibrosis and oedema, or changes in the
      echogenicity of the duct wall. At present in the diagnosis of early stages of
      chronic pancreatitis most probably a combination of the method evaluating the
      exocrine secretory capacity of the pancreas and sensitive imaging methods (ERCP)
      will be most satisfactory. Further studies will show whether and when EUS could
      replace ERCP.

PMID- 11344631
TI  - [A study of the United Kingdom Prospective Diabetes Study and its results].
AB  - This article summarizes the results of the United Kingdom Prospective Diabetes
      Study, which monitored more than 4,000 patients with diabetes mellitus type 2 for
      an average period of 11 years after the establishment of the diagnosis. The
      results of this study are as follows: A lower number of microvascular, but not
      macrovascular complications was established in the intensively treated patients
      (fasting plasma glucose less than 6 mmol/l) than was the case in the
      conventionally treated patients (fasting plasma glucose concentration less than
      15 mmol/l). No differences in efficacy in reducing glycaemia were found in the
      intensive treatment between sulphonylurea, insulin and metformin, but all of them
      were more effective than diet alone. However, mean baseline glucose
      concentrations in all treatment groups steadily increased over the entire study
      period. The reduction of macrovascular complications was seen only in the group
      of obese diabetics with metformin monotherapy. The great reduction of
      macrovascular complications was seen in the group of good blood pressure, and no
      differences between ACE-inhibitor and betablocker were established. There were no
      more ischemic complications among patients receiving sulphonylurea's medication
      and there were no more atherosclerotic complications in patients receiving
      insulin.

PMID- 11344632
TI  - [Thrombotic complications in patients with malignant diseases].
AB  - The incidence of thromboembolic disease (TED) in malignant diseases is high and
      is often the cause of death in these patients. The most important thrombogenic
      factors are changes of the coagulation system, venostasis, changes in the
      function and structure of the endothelium and the influence of specific anti
      tumour therapy. The most frequent clinical manifestation is phlebothrombosis of
      the lower extremity. Diagnostic procedures in detection of thrombosis do not
      differ fundamentally from standard procedures (clinical examination, duplex
      sonography, phlebography, possibly pulmonary scintigraphy). More intensive
      prophylaxis of TED is necessary under certain conditions (surgical treatment,
      immobilization, chemotherapy). Therapeutic patterns with heparins, possibly
      thrombolytics, are common but subsequent anticoagulation treatment must be
      provided as long as the active stage of the neoplastic disease persists, in
      particular if the patient is treated with cytostatics. When anticoagulation
      treatment is contraindicated and there is a general favourable prognosis,
      implantation of caval filters is an adequate provision. New findings indicate the
      possible anti-tumourous action of low-molecular heparins, but these are only
      initial observations.

PMID- 11344633
TI  - [Endothelins--physiology, pathophysiology and importance in arterial
      hypertension].
AB  - Endothelins are peptide tissue hormones with a powerful vasoconstrictor effect.
      The most important one among them, endothelin-1, is the most powerful
      vasoconstrictor substance in the human organism which causes constriction of the
      blood vessels, in particular renal, coronary, pulmonary and cerebral arteries,
      bronchioles, and inhibits the secretion of atrial natriuretic factor and
      vasopressin. Because of these effects importance in the pathogenesis of some
      diseases is ascribed to it, e.g. myocardial infarction, cardiac failure, asthma
      bronchiale, Raynaud a syndrome, renovascular disease, cyclosporin-induced
      nephrotoxicity and cerebrovascular attacks. Although there is little direct
      evidence on the role of endothelins in arterial hypertension, some authors prove
      its importance at least in some of its forms, e.g. salt sensitivity, or in
      complications of hypertension. The results of experimental and human studies with
      antagonists of endothelin receptors and endothelin-converting enzyme blockers
      also support the role of endothelin in the pathogenesis of hypertension. The use
      of these antagonists in the treatment of hypertension calls however for further
      long-term studies.

PMID- 11344634
TI  - [Acute pancreatitis as the road to diagnosis of primary hyperparathyroidism].
AB  - The authors present the case of a 78-year-old female patient who was admitted on
      account of acute pancreatitis complicated by acute myocardial infarction. The
      authors detected in the patient a serum repeatedly high calcium levels and high
      levels of intact parathormone. Scintigraphic examination revealed marked foci in
      the middle of the neck at the level of the inferior pole of the thyroid gland.
      These examinations confirmed the diagnosis of primary hyperparathyroidism. In
      view of the patient a serious condition, conservative treatment of hypercalcaemia
      and acute pancreatitis and myocardial infarction was started. The patient was
      released into domiciliary care after 40 days in hospital in a state of
      cardiopulmonary compensation, with cystic transformation of the pancreas and
      without signs of acute pancreatitis.

PMID- 11344635
TI  - [Early renal failure caused by mesalazine].
AB  - The author describes a case of early onset of asymptomatic renal insufficiency in
      a young patient with ulcerative colitis, treated by large doses of mesalazine.
      After discontinuation of the drug rapid restoration of renal functions occurred.
      Contrary to all hitherto published cases, this patient developed renal failure
      very soon. Urea serum levels reached pathological values after 27 days and the
      creatinine level already 15 days after the onset of mesalazine administration.
      The renal affection was unequivocally confirmed by examination of the urine
      (semiquantitative and quantitative) and dynamic functional scintigraphy.

PMID- 11344636
TI  - [Who was Mr. McBean and what resulted from his death?].
AB  - Authors present a historical overview of multiple myeloma. The first well-known
      case of multiple myeloma was that of Mr. McBean described in 1846, 1847, and 1850
      by John Darlympe, Henry Bence Jones, and William MacIntyre. The term multiple
      myeloma dates from 1873, and was introduced by von Rusitzky. In 1889, Otto Kahler
      published the case report about Dr. Loos, his patient with multiple myeloma. In
      1895, Marschalko described the essential characteristics of plasma cells. Authors
      present other interesting early cases of multiple myeloma and diagnostic advances
      in this disease.

PMID- 11344638
TI  - [Dr. Rudolf Vanysek, DrSc. (1876-1957)].

PMID- 11344639
TI  - [Should we treat the symptom or the disease? Treat the patient].

PMID- 11344640
TI  - [Longitudinal trends of total and HDL cholesterol in a representative population
      sample in the Czech Republic].
AB  - Cardiovascular diseases are the main cause of death in the Czech Republic. Since
      1984 there is a decline of the total and cardiovascular mortality in the CR which
      is due to a decline of the mortality from IHD and cerebrovascular disease. Within
      the framework of the MONICA project in 1985, 1988 and 1992 in six districts of
      the CR screening examinations of cardiovascular disease risk factors were made.
      For examination always 1% of the population aged 25-64 years (random sampling)
      was invited. In 1997 and 1998 a similar cross-sectional surmy was made in nine
      districts of the CR. A total of 3,209 subjects were examined. In 1985-1997/98 in
      the representative population samples of six districts of the CR there was a
      significant decline of total cholesterol (men from 6.21 +/- 1.29 to 5.65 +/- 1.15
      mmol/l, p < 0.001, women from 6.18 +/- 1.26 to 5.53 +/- 1.21 mmol/l, p < 0.001
      and the total cholesterol/HDL ratio (men from 4.94 +/- 1.83 mmol/l to 4.66 +/-
      1.46, p < 0.001, women from 4.14 +/- 1.32 to 3.89 +/- 1.30 mmol/l p < 0.001).

PMID- 11344641
TI  - [Pathophysiologic aspects of hyperlipoproteinemias].
AB  - Elevated LDL-cholesterol levels and reduced HDL-cholesterol levels are
      independent risk factors for the development of ischaemic heart disease.
      Atherosclerosis is promoted also by some particles rich in triacylglycerols, in
      particular intermediate density lipoproteins (IDL), partly also very low density
      lipoproteins (VLDL). The risk of IHD is enhanced also by subfractions of LDLIII
      and protracted postprandial lipaemia, characterized by an increased concentration
      of remnants of chylomicrons. An independent risk factor is also an increased
      concentration of lipoprotein(a). When evaluating the cardiovascular risk of an
      actual patient it is always necessary to consider in addition to blood lipid
      levels also other non-lipid risk factors.

PMID- 11344642
TI  - [Nutritional aspects of hyperlipoproteinemias].
AB  - The article deals with contemporary views on the impact of different nutritional
      substrates important for the construction of diets for patients with primary and
      secondary hyperlipoproteinaemia, explanation of different provisions and
      instructions according to which the physician or dietitian can prepare individual
      diets for normosthenic and obese patients, incl. calculation of the energy value
      of the diet. The author emphasizes also some new aspects of nutritional
      pharmacology useful not only for the treatment of hyperlipoproteinaemia but also
      for prevention of thrombogenic complications and adverse vasomotor reactions in
      patients with affections of the cardiovascular system.

PMID- 11344643
TI  - [Lipids and chronic heart failure].
AB  - The causes of chronic heart failure at the end of the 20th century are quite
      different from those 30 or 50 years ago. The last data from the Framingham study
      indicate that ischaemic heart disease and/or hypertension are the main cause in
      as many as 90% patients. The prevalence of chronic heart failure in European
      countries, 0.4-2%, implies 40-200,000 patients in the Czech Republic.
      Pharmacological treatment during the last 15 years revealed clearly that the
      drugs of choice which prolong life are inhibitors of the angiotensin converting
      enzyme (ACE-I) which are combined with other drugs as needed by the patient. A
      combination of five drug groups (ACE-I, digitalis, diuretics, beta-blockers, and
      spironolactone) are nowadays the basic treatment. In the 4S study (Scandinavian
      Simvastatin Survival Study--4,444 patients with ischaemic heart disease followed
      up for 5.4 years) 412 (9.2%) developed chronic heart failure requiring treatment,
      i.e. 228 (10.3%) in the placebo group and 184 (8.3%) patients in the group
      treated with simvastatin (p < 0.015). In the group of patients with signs of
      heart failure 73 of 228 died the placebo group and 47 of 184 in the simvastatin
      group (reduction of the relative risk by 19%, p = 0.014), to save one life (NNT)
      it was necessary to treat 15 patients for a period of 5 years. From the aspect of
      the number of patients it was necessary to treat six times as many patients
      without heart failure than with heart failure to save one life in five years.
      Hypolipidaemic treatment should be an obvious part of treatment of heart failure
      due to ischaemic heart disease. Hyperlipoproteinaemia is described in 60-80%
      patients after transplantation of the heart. Treatment involves diet, reduction
      or discontinuation of corticoids, maintenance of cyclosporin at the lowest
      effective level and treatment wit statins.

PMID- 11344644
TI  - [Lipids and acute coronary syndromes].
AB  - Eccentric atherogenic plaques which cause only insignificant narrowing of the
      diameter of coronary arteries are the cause of 60-80% of all acute coronary
      syndromes. The plaque becomes unstable (vulnerable) due to cytokines released by
      macrophages in the lipid rich core. Weakening of the fibrous capsule of the core
      then leads to rupture of the plaque and subsequently to intracoronary thrombosis
      with a wide spectrum of ischaemia or even necrosis of the myocardium. Secondary
      preventive studies (4S, LIPID, CARE), morphological non-mortality studies (e.g.
      AVERT, REGRESS, LCAS) and primary preventive studies (WOSCOPS, AFCAPS/TexCAPS)
      revealed that statins reduce significantly, as compared with placebo, total and
      LDL-cholesterol by 20-35% and lead in subsequent years to a significant decline
      of the relative risk of the general and coronary mortality and morbidiy by 20
      40%. They prevent progression and may lead to regression of coronary sclerosis.
      They do not act by mere reduction of the cholesterol level but also by their
      extralipid effects which stabilize the plaque. 80% of patients with coronary
      syndrome have cholesterol levels between 6.0 and 7.5 mmol/l, similarly as ca 40%
      of healthy middle aged persons. The difference is in the risk caused either by
      the presence of ischaemic heart disease or in healthy subjects by the cumulation
      of several coronary risk factors. A special risk group are the remaining 20%
      patients. They include subjects with a cholesterol level above 8 mmol/l who must
      be treated more aggressively, similarly as patients after a venous aortocoronary
      bypass. Subjects with slightly elevated LDL-cholesterol values but high
      triacylglycerol levels and lower HDL-cholesterol levels have also an atherogenic
      risk. This applies not only to postmenopausal women, elderly people, obese and
      diabetic subjects, hypertensive subjects with insulin resistance but also to
      young subjects. In the latter reduction of triacylglycerols is indicated. In
      coronary patients a combination of statins and fibrates may be used. Basic
      hypolipidaemic treatment for reduction of the atherothrombotic risk are statins.
      Despite statin treatment the prospective mortality and morbidity of coronary
      patients is still high and it is necessary to make an effort to achieve target
      lipid levels. Recent studies provide new findings, further progress and stricter
      therapy are foreseen.

PMID- 11344645
TI  - [Lipids and heart valve defects].

PMID- 11344646
TI  - [Lipids and atherosclerosis of the peripheral vessels].
AB  - The authors present a review of information on the incidence ef obliterations of
      peripheral vessels, incl. their own experience, with a group of diabetic
      patients. Attention is paid to the pathophysiology of affections of peripheral
      vessels. In the final part data on the relationship of lipids or their fractions
      and the development of obliteration of peripheral vessels are presented.

PMID- 11344647
TI  - [Dyslipoproteinemia and diabetes mellitus].
AB  - Diabetes mellitus is, as compared with the non-diabetic population, associated
      with a much higher mortality of ischaemic heart disease and other cardiovascular
      diseases. In this risk participates in a major way also diabetic dylipidaemia.
      The latter is characterized in particular by hypertriglyceridemia which reflects
      the increase of VLDL and IDL lipoproteins. Elevated and prolonged postprandial
      lipaemia participates in the development of qualitative lipoprotein changes.
      Highly athergenic "small dense LDL" are formed which are liable to an oxidative
      modification and are then in an unregulated manner taken up in the vascular wall.
      Reduction of HDL-cholesterol and a change in the different HDL sub-populations
      leads then to a deteriorated reverse cholesterol transport. Type 2 diabetes
      mellitus is associated with dyslipidaemia in the majority of patients even under
      conditions of satisfactory compensation of diabetes, in particular during the
      postprandial stage. On the other hand, in type 1 diabetes the lipid values
      usually become normal when the blood sugar level becomes normal, however
      qualitative changes of lipoproteins frequently persist. Increased glycation and
      oxidation of lipoproteins is a common sign of both types of diabetes. For
      prevention of cardiovascular complications treatment of diabetic dyslipidaemia is
      at least equally important as efforts to achieve optimal compensation of
      diabetes. Successful treatment of diabetic dyslipidaemia includes efforts to
      achieve compensation of diabetes, optimation of body weight, increase of physical
      activity, modification of diet, treatment of other secondary causes of
      hyperlipidaemia, and if these provisions are not successful, pharmacological
      hypolipidaemic treatment. The risk of macrovascular complications is so high in
      diabetics that according to recent knowledge it is not necessary to differentiate
      between primary and secondary prevention but aggressive treatment is necessary to
      achiebe target values of total cholesterol < 5.0 mmol/l and LDL-cholesterol < 3.0
      mmol/l. Triglycerides > 2 mmol/l and HDL-cholesterol < 1 mmol/l are signs of a
      high cardiovascular risk. Optimation of the whole lipid profile is ideal.

PMID- 11344648
TI  - [Dyslipoproteinemia and chronic kidney failure].
AB  - Lipoprotein abnormalities are a regular part of metabolic changes associated with
      chronic renal failure. The character of dyslipoproteinaemia changes with the
      severity of disorders of renal functions, from initial deviations in the
      composition and distribution of circulating lipoprotein particles (a decline of
      glomerular filtration to 0.7-0.8 ml/s) to differently expressed changes of plasma
      lipid concentrations in terminal renal failure. The basis of the pathogenetic
      mechanism of these lipid abnormalities is the negative effect of the uraemic
      environment on the formation and catabolism of triglyceride-risk lipoproteins and
      on the function of the reverse cholesterol transport. An important part is also
      played by the modification of lipoprotein particles by oxidation and glycation.
      To a different extent also the nutritional status is manifested via the
      unfavourable composition of dietary fats, reduced effectiveness of antioxidant
      factors and in some instances also carnitine deficiency. Haemodialysis treatment
      and in particular peritoneal dialysis modify these lipid abnormalities. From the
      quantitative aspect renal dyslipoproteinaemia is not very striking, despite this
      its quantitative changes are important. It may have a negative impact on the
      progression of renal disease by its participation in the development of
      glomerular sclerosis and tubulointerstitial fibrosis. As one of the important
      risk factors it participates also in the acceleration of atherosclerosis in
      patients with chronic renal failure and in their much higher cardiovascular
      mortality as compared with the general population. These factors justify efforts
      to influence uraemic dyslipoproteinaemia. Fibrates or statins are indicated in
      conjunction with the supporting effect of diet and modification of the dialysis
      regimen. In tables and figures some results assembled by the authors are
      presented obtained in a group of dialyzed patients (characteristic of the lipid
      profile under basal conditions on fasting and after an oral lipid load and
      experience with influencing dysliopoproteinaemia by fenofibrates and
      atorvastatin).

PMID- 11344649
TI  - [Lipid disorders in liver diseases].
AB  - The liver is the main organ of cholesterol, triglyceride metabolism and
      lipoprotein synthesis. In diffuse parenchymatous diseases which lead to cirrhosis
      of the liver a decline of VLDL and HDL particles occurs, as well as a decline of
      apo-B, apo-E lipoprotein (a). In cholestatic diseases the levels of free
      cholesterol, phospholipids and sometimes also triglyceride levels rise, in the
      termonal stage they decline again. A specific marker of cholestasis is the
      presence of abnormal lipoprotein X, which is formed from non-esterified
      cholesterol and phsopholipids regurgitating from bile. Primary lipid disorders
      may then cause liver disease--steatosis. The main risk factors are
      hypertriglyceridaemias. In the pathogenesis of liver steatosis in particular an
      increased supply of fatty acids into the liver, is involved, as well as defects
      in the process of VLDL synthesis and triglyceride release from the liver into the
      circulation. Hypercholesterolaemia is not a risk factor of steatosis.

PMID- 11344650
TI  - [Lipid disorders after organ transplantation].
AB  - Transplantations are a routine method of treatment of chronic and acute organ
      failure. Changes in the therapeutic strategy led to improvement of organ and
      patient survival immediately after transplantation and during the early post
      transplantation period. Medium-term and long-term results of organ survival
      improved less markedly. Chronic dysfunction and death are the most frequent
      causes of loss of a transplanted organs one year after transplantation. Chronic
      dysfunction has immunological and non-immunological causes. An important risk
      factor is hyperlipidaemia. Therapy must be started as soon as possible. It
      threatens the patients prognostically more than the normal population. Dietetic
      treatment and optimal immunosuppression are essential therapeutic steps which
      have a favourable effect on the general prognosis. A great hope in
      transplantology are statins. They have not only a positive effect on blood lipids
      but also an immunosuppressive and antiproloferative effect which is very
      favourable for the prevention of transplantation vasculopathies. Most probably
      their group effect is involved. Statins combined with classical immunosuppressive
      preparations reduce the incidence of acute rejections. The effect on lipid
      levels, the frequency of rejections and development of vasculopathies makes
      statins important adjuvant preparations in transplantology.

PMID- 11344651
TI  - [Dyslipoproteinemia in elderly patients].
AB  - Dyslipoproteinaemia as one among classical risk factors of atherosclerotic
      cardiovascular diseases has been involved also in the aged. The predictive value
      of total cholesterol, LDL-cholesterol, HDL-cholesterol, triacylglycerols and
      lipoprotein (a) is preserved. There are several objective data from post-hoc
      analyses of prospective clinical studies AFCAPS/TexCAPS, 4S, CARE, LIPID a
      WOSCOPS, which addressed the need of treatment of dyslipoproteinaemia in the
      aged. The guidelines are not unique, but they stress an individual approach. We
      usually continue to treat genetic forms of dyslipidaemia. Candidates of treatment
      are also patients with diagnose of coronary heart disease (CHD) and sublinic form
      of CHD, where the treatment has been effective within two years and lead to
      decrease of CHD risk up to 45%. The individuals with CHD and other CHD risk
      factors absent would be treated less often. The diet is an basic treatment option
      of hypolipidemic intervention in the elderly. We do not omit exercise. The
      pharmacotherapy of dyslipidaemia is used for the individuals with high risk. We
      usually start with lower dose of fibrates or statins and monitor for adverse
      effects of such therapy.

PMID- 11344652
TI  - [Therapeutic goals in hyperlipoproteinemia].
AB  - In the treatment of hyperlipoproteinaemias (HLP) our main effort should be
      treatment of the patient and not achievement of defined biochemical values. The
      basic goals of HLP treatment can be defined on the basis of results of
      intervention studies as follows: reduction of general mortality, reduction of
      morbidity from IHD, reduction of the incidence of CMP, improved course of
      ischaemia of the lower extremities, better quality of life of patients with
      cardiovascular disease and reduced necessity of revascularization surgery. Even
      if we shall assume that the positive effect of treatment with HLP are in the
      first place optimization of the lipid spectrum, in particular a drop of total and
      LDL cholesterol, we cannot overlook so-called "non-lipid" effects of
      hypolipidaemic agents, in particular statins. In the treatment of patients with
      HLP it is important in the first place to evaluate the comprehensive risk of the
      patient, nevertheless it is possible to define "target values" e.g. according to
      recommendations of "European societies". Even these target values may be the
      subject of further discussions. It may be however stated that the objective is
      that total cholesterol should be less than 5 mmol/l, LDL cholesterol less than 3
      mmol/l and triglycerides less than 2 mmol/l, HDL cholesterol higher than 1
      mmol/l. Attention should be however drawn to the fact that evidence is increasing
      that in particular patients with already manifest IHD will benefit from even more
      aggressive treatment and attempts to achieve minimal lipid and lipoprotein
      values. LDL cholesterol should be reduced to 2.5 mmol/l and triglycerides should
      be below 2 mmol/l. It is a problem how to achieve these values. The strongest
      evidence is in favour of statin administration. On the other hand it is important
      to mention that optimation of the lipid and lipoprotein spectrum may be more
      important than prescription of a drug from a certain group.

PMID- 11344653
TI  - [Effect of nonpharmacologic intervention on lowering plasma cholesterol levels].
AB  - Our study focused on the effect of non-pharmacological intervention based on the
      modification of dietary habits and increasing physical activity on the level of
      total plasma cholesterol. SAMPLE AND METHODS: Intervented sample was created by
      279 highly motivated healthy adults from Brno (168 women and 111 men) of average
      age 43.5 +/- 10.3 years and average level of total plasma cholesterol 6.1 +/-
      0.75 mmol/l and HDL-cholesterol 1.04 +/- 0.14 mmol/l. After medical and life
      style history assessment, followed by clinical and biochemical checking and
      evaluation the risk from the life-style and biochemical and clinical parameters,
      the participants were individually informed about recommendations. These
      recommendations regarded detailed changes of dietary habits, quantified by the
      recommended number of servings of basic food groups and sub-groups daily and also
      increasing physical activity. RESULTS: After 3 months the changes of biochemical
      parameters were evaluated. After our non-pharmacological intervention we founded
      significantly lower average level of total plasma cholesterol 5.36 +/- 1.24
      mmol/l (p < 0.001) and higher level of HDL-cholesterol 1.16 +/- 0.14 mmol/l. The
      level of TG's did not change significantly neither in whole sample, nor in the
      sub/sample of women and men. 26% of our sample was resistant to the intervention
      (the difference in the total cholesterol level between 2 assessment was lower
      than 0.5 mmol/l). No significant difference was found between men and women
      regarding the reaction of plasma lipoproteins. DISCUSSION AND CONCLUSIONS: Our
      results justify the adequacy and appropriety of primary preventive advising
      focusing on decrease of the risk of premature death using non-pharmacological
      intervention in highly motivated people with good compliance and sufficient
      responsibility for their personal health.

PMID- 11344654
TI  - [Pharmacotherapy of hyperlipoproteinemia].
AB  - Hyperlipoproteinaemia is one of the main risk factors of ischaemic heart disease.
      The centre of gravity of its pharmacotherapy with hypolipidaemic agents is
      secondary prevention of ischaemic heart disease. In patients in primary
      prevention of ischaemic heart disease pharmacotherapy is indicated only in case
      of high risk, if non-pharmacological treatment does not lead to achievement of
      target values of blood lipids. Available hypolipidaemic drugs on our market
      include statins, fibrates and resins. A suitable preparation should be selected
      with regard to the type of hyperlipidaemia. A constant part of treatment with
      hypolipidaemic drugs must be also non-pharmacological treatment which in the
      majority should precede pharmacotherapy.

PMID- 11344655
TI  - [Childbirth in Denmark. Centralization or not?].

PMID- 11344656
TI  - [Gallstones and pregnancy].

PMID- 11344657
TI  - [Whiplash. Epidemiology, diagnosis and treatment].
AB  - Recent years have seen an increasing number of car occupants with neck complaints
      following a car collision and a declining number of persons involved in car
      crashes--a relationship that is not well understood. Presumably less than 5% will
      suffer from persistent, (long-lasting), disabling neck pain. Although mostly men
      are involved in motor vehicle accidents, an equal number of men and women seek
      emergency care, but it is mostly women, who have persistent (long-lasting) neck
      complaints after a car collision. In general, there is no documentation of
      specific injury to the brain or spinal cord from a simple whiplash (WAD 1-3).
      Whiplash-related neck pain is caused by a distortion of the cervical spine, and,
      as such, should be interpreted as a benign condition with a good prognosis.
      Whiplash should be considered a risk factor rather than a medical diagnosis. The
      association between cause (whiplash mechanism) and effect (symptoms) is poor.
      Persistent (long-lasting) health problems from a whiplash should be treated like
      other post-traumatic conditions, and need a bio-psycho-social approach.

PMID- 11344658
TI  - [Uncomplicated gallstone disease and pregnancy].
AB  - Pregnancy is associated with an increased incidence of gallstones. However, most
      gallstones disappear spontaneously after pregnancy without having given any
      symptoms. New knowledge regarding the pathophysiology confirms changes in the
      motility of the gallbladder and the flow dynamics and lithogenicity of the bile.
      The studies have also shown, that these changes resolve completely after labour,
      which might explain the disappearance of most of the gallstones. These conditions
      support a conservative attitude towards treatment of gallstone disease during
      pregnancy. In case cholecystectomy is indicated, laparoscopic intervention seems
      safe during pregnancy and most optimal during the second trimester where the
      organogenesis of the fetus is completed and where the size of the uterus does not
      interfere with the operation technically. Laparoscopic cholecystectomy should
      under all circumstances be done in departments with routine in laparoscopic
      operations and with the possibility of gynaecological assistance, in case it is
      needed.

PMID- 11344659
TI  - [Obstetrics in Denmark. The role of surgical maternity wards in Denmark].
AB  - INTRODUCTION: About 13.5% of the deliveries in Denmark take place on maternity
      wards which lie within the bounds of a surgical department, mainly at small
      general hospitals. The Danish Society for Obstetrics and Gynaecology has
      recommended closing all such surgical maternity wards. This prompted a comparison
      of birth outcomes for women who live in municipalities, which are served by a
      surgical maternity ward compared to the rest of the Danish women. METHODS: The
      data was obtained as a random sample of 74,000 deliveries from The Danish Birth
      Registry. The main outcome variables were perinatal deaths and operative
      deliveries. RESULTS: No difference was found in the perinatal mortality, the
      crude OR being 1.03 (95% CI: 0.87-1.14). Logistic regression analysis was used to
      correct for the effect of confounding factors resulting in an adjusted OR = 1.13
      (95% CI: 0.92-1.38). CONCLUSION: The investigation does not confirm the need for
      further centralisation of maternity care as a means of lowering the perinatal
      mortality in Denmark.

PMID- 11344660
TI  - [Cases of measles in Denmark are caused by reintroduction of virus from abroad].
AB  - Measles vaccination was implemented in the child vaccination programme in Denmark
      in 1987 and produced a rapid decline in the incidence. Few cases were recorded
      annually until 1999. The measles virus isolated in Denmark during 1997-1998 was
      compared by partial sequencing of the haemagglutinin-coding region with Danish
      strains from the prevaccination era collected in 1965-1983, as well as with
      representatives of globally circulating strains of today. The dissimilarity of
      the prevaccination era strains identified in Denmark in 1997-1998 along with the
      similarity of these five strains with globally circulating strains at present,
      substantiate the conclusion that there is no persistent circulation of the
      measles virus in Denmark.

PMID- 11344661
TI  - [Designer drugs in Jutland].
AB  - INTRODUCTION: The aim of this investigation was to examine illegal tablets and
      capsules seized in Jutland, the western part of Denmark, during the period 1995
      1999. The drugs are described according to technical appearance (colour, logo,
      score, diameter) and content of synthetic drugs. MATERIAL AND METHODS: All
      illegal tablets and capsules received during the period 1995-1999 (109 cases
      containing 192 different samples) were examined. RESULTS: MDMA was the most
      common drug and was seen during the entire period. Amphetamine was the second
      most common drug and has been frequently detected during the the last two years.
      Drugs like MDE, MBDB, BDB, and 2-CB were rarely seen and they disappeared quickly
      from the illegal market. MDA appeared on the market at the end of 1999. Only 53%
      of the tablets contained MDMA as the sole drug. Eighty-one percent of the
      tablets/capsules contained only one synthetic drug, whereas 13% contained a
      mixture of two or more synthetic drugs. Six per cent of the samples did not
      contain a euphoric drug/designer drug. The content of MDMA, MDE, and amphetamine
      in the tablets varied greatly. DISCUSSION: MDMA is apparently the drug preferred
      by the users, but still only half of the tablets contained MDMA as the only drug.
      The rest of the tablets contained either another synthetic drug or a mixture of
      drugs. In conclusion, the increasing supply of various drugs with different and
      unpredictable effects and of miscellaneous quality brings about the risk of
      serious and complicated intoxications.

PMID- 11344662
TI  - [Fatal ecstasy intoxication].
AB  - A case of full-blown, lethal MDMA intoxication, owing to abuse of ecstasy is
      described. The increasing popularity of ecstasy among young, otherwise healthy,
      people prompts health care providers to recognise better the symptoms of systemic
      intoxication in order to initiate early treatment, such as rehydration, cooling
      in cases of hyperthermia, seizure treatment, correction of cardiac arrhythmia,
      and metabolic and electrolyte abnormalities.

PMID- 11344663
TI  - [Primary, small cell carcinoma of the urinary bladder].
AB  - Primary small cell carcinoma of the bladder (SC) is a rare malignant tumour,
      accounting for less than 2% of all malignant tumours of the urinary bladder. SC
      is an extremely biologically aggressive tumour with early progression and short
      survival. This paper describes one case of small cell carcinoma.

PMID- 11344664
TI  - [Picture of the month: lymph node tuberculosis].

PMID- 11344665
TI  - [Continuous blood glucose monitoring].

PMID- 11344666
TI  - [Human albumin to critically ill patients].

PMID- 11344667
TI  - [Mortality following administration of human albumin].

PMID- 11344668
TI  - [The clock-face test].

PMID- 11344669
TI  - Repeated ultrasound guided fetal injections of corticosteroid alter nervous
      system maturation in the ovine fetus.
AB  - INTRODUCTION: Recent studies in sheep have shown that repeated maternal
      injections of betamethasone are associated with adverse effects within the
      nervous system. Repeated fetal injections of betamethasone achieve serial
      improvements in preterm lung function in sheep and are a possible alternative to
      repeated maternal therapy. We have evaluated the effect of repeated fetal
      administration of betamethasone on nervous system maturation in an ovine model.
      METHODS: Date-mated ewes (n = 48) were randomized to receive ultrasound-guided
      fetal injections of betamethasone or saline between days 104 to 124 of gestation
      and were delivered by cesarean section on day 125 or 145 (term = 150). Optic and
      sciatic nerves were prepared for light and electronmicroscopy. Eye diameters were
      measured and transverse sections of retinae were evaluated. Data were analyzed
      using a mixed model analysis of variance. RESULTS: Repeated fetal administration
      of corticosteroid did not significantly affect optic nerve myelination but
      resulted in significant delays in sciatic axonal growth (p < 0.02) and retinal
      maturation (p < 0.04). The process of performing repeated fetal injections also
      significantly affected some retinal parameters. CONCLUSION: Repeated fetal
      administration of betamethasone alters some aspects of nervous system maturation
      in sheep. It is premature to plan trials of repeated fetal corticosteroid therapy
      in humans.

PMID- 11344670
TI  - Incidence and birth weight characteristics of twins born to mothers aged 40 years
      or more compared with 35-39 years old mothers: a population study.
AB  - OBJECTIVE: To compare the incidence of twin births and their birth weight
      characteristics in mothers aged > or = 40 years with those of mothers aged 35-39
      years. METHODS: We used a population-based cohort of Israeli twins delivered
      between 1993-98 to compare birth weight characteristics of 510 and 2102 twin
      pairs delivered to mothers aged > or = 40 years (cases) and 35-39 years
      (controls), respectively. RESULTS: The incidence of twin mothers aged 40 years or
      more increased 50% during the study period, ten times more than mothers aged 35
      39. There were significantly more nulliparas (P < .001, OR 1.54, 95% CI 1.2, 1.9)
      and more para > or = 4 (P < .004, OR 1.38, 95% CI 1.1, 1.7) among older mothers.
      Irrespective of parity, there were no significant differences between mean twin
      birth weight, total twin birth weight < 3000 g, 3000-4999 g, and > or = 5000 g,
      and frequencies of very low birth weight neonates. CONCLUSIONS: Twin birth at the
      age of > or = 40 years is significantly more likely among either nulliparas or
      para > or = 4. Birth weight characteristics of twins delivered to mothers aged >
      or = 40 years are not different from those delivered to 35-39 years old mothers.

PMID- 11344671
TI  - Lipopolysaccharide stimulation of 70 kilo Dalton heat shock protein messenger
      ribonucleic acid production in cultured human fetal membranes.
AB  - OBJECTIVE: The 70 kilo Dalton heat shock protein is up-regulated when cells are
      under physiological stress. It prevents protein denaturation and incorrect
      polypeptide assembly, and inhibits apoptosis as well as the transcription of
      genes coding for pro-inflammatory cytokines. To evaluate if up-regulation of heat
      shock protein 70 can occur during pregnancy, we examined whether addition of
      bacterial lipopolysaccharide to human amniochorion membranes in vitro stimulated
      heat shock protein 70 gene transcription. MATERIALS AND METHODS: Amniochorionic
      membranes (n = 5), collected at the time of elective repeat cesarean section
      prior to labor from normal term gestations, were placed in an organ explant
      system. After 48 hour in culture, the membranes were stimulated with
      lipopolysaccharide for 24 hours. Total RNA was extracted and subjected to an
      oligo dT primed reverse transcriptase reaction followed by polymerase chain
      reaction (PCR) using heat shock protein 70 specific primers. PCR products were
      hybridized with biotinylated internal probes and identified by enzyme-linked
      immunosorbent assay (ELISA). Results were analyzed by Mann-Whitney U test. A p <
      0.05 was significant. RESULTS: Heat shock protein 70 messenger RNA was expressed
      by all fetal membrane preparations both prior to and following in vitro culture.
      Addition of lipopolysaccharide increased the concentrations of heat shock protein
      70 messenger RNA in each sample tested from a mean of 35.5 +/- 29.6 ng/milliliter
      (12.1-80.1 ng/milliliter) to 169.6 +/- 69.9 ng/ml (51.7-218.2 ng/milliliter) (p =
      0.03). CONCLUSION: Human fetal membranes constitutively express heat shock
      protein 70 messenger ribonucleic acid. Bacterial lipopolysaccharide markedly
      stimulated heat shock protein 70 messenger RNA gene transcription in human fetal
      membranes. Thus, heat shock protein 70 is inducible in fetal membranes and may
      facilitate fetal survival under adverse conditions.

PMID- 11344672
TI  - Effect of positive end expiratory pressure on functional residual capacity and
      compliance in surfactant-treated preterm infants.
AB  - Positive end expiratory pressure is routinely used when ventilating preterm
      infants. Elevation of PEEP increases lung volume, as does surfactant treatment.
      The purpose of this study was to investigate the effect of various levels of PEEP
      within the range of 0.2 to 0.4 kPa on lung volume, compliance and gas exchange.
      We measured functional residual capacity, compliance of the respiratory system
      and arterial blood gases in 20 infants (median birth weight 1240 g, range 660
      1690 g; median gestational age 28 weeks, range 24-32 weeks; postnatal age 3-4
      days). The infants were studied at 72 hours after their last dose of natural
      surfactant. At this time the patients were routinely nursed at 0.3 kPa of PEEP,
      the PEEP level was lowered to 0.2 kPa or raised to 0.4 kPa in random order. The
      PEEP level was then changed to the third level 0.4 kPa or 0.2 kPa. Each new
      setting was maintained for 20 min before FRC, compliance and blood gases were
      measured. FRC was assessed using SF6 washout technique. Increasing PEEP from 0.2
      to 0.3 to 0.4 kPa resulted in increases in FRC (p < 0.01) and oxygenation (ns) in
      all infants. In 16 infants compliance decreased and paCO2 increased with
      elevation of PEEP. Only in 4 infants compliance increased and CO2 fell.
      CONCLUSION: In the majority of our infants reduction of PEEP from 0.4 to 0.2 kPa
      resulted in increases in compliance and CO2 reduction. Our results might suggest
      that relatively low levels of PEEP < 0.3 kPa may be appropriate at 72 hours after
      surfactant replacement. Furthermore, these results underline the importance of
      PEEP test in clinical practice.

PMID- 11344673
TI  - Neonatal nucleated red blood cell counts in twins.
AB  - We counted nucleated red blood cells (NRBC) per 100 white blood cells (WBC) in
      the umbilical cord blood from 98 twins born to 49 women with uncomplicated twin
      pregnancies at > or = 34 weeks of gestation to better characterize NRBC in twins.
      Twelve women with monochorionic (MC) placentas and 37 with dichorionic (DC)
      placentas gave birth at 36.7 +/- .9 and 36.5 +/- 2 weeks of gestation,
      respectively. All twins were born with an Apgar score of > or = 7 at 1 min. Log10
      (NRBC/100 BC) in 98 twins exhibited a nearly normal distribution, and was
      significantly associated with gestational age for both MC (r = -0.457, p = 0.025)
      and DC twins (r = - 0.275, p = 0.018), and with birth weight for both MC (r = 
      0.682, p < 0.001) and DC twins (r = -0.336, p = 0.003). Log10 (NRBC/100 WBC)
      tended to be larger in smaller twins than in larger twins in the MC group, and
      significantly larger in smaller twins than in larger twins in the DC group (p <
      0.05). Intertwin difference in Log10 (NRBC/100 WBC) was defined as the value of
      Log10 (NRBC/100 WBC) of the smaller twin minus Log10 (NRBC/100 WBC) of the larger
      twin, and became greater with increasing intertwin difference in birth weight (r
      = 0.411, p = 0.003). These findings suggest that neonatal NRBC reflected
      gestational age and birth weight in twins. This preliminary observation using a
      small number of twins suggests that the smaller twin may have experienced a
      relative lack of oxygen compared with the larger twin in utero.

PMID- 11344674
TI  - Normalisation of a severely abnormal ductus venosus Doppler flow velocity
      waveform in a growth-retarded fetus with absent end-diastolic flow in the
      umbilical artery and congenital anomalies.
AB  - Doppler recordings of fetal venous blood flow seem to be superior to arterial
      velocimetry and CTG concerning the prediction of fetal outcome and optimal time
      of delivery in pregnancies with fetal growth retardation and AREDV. An
      improvement of arterial Doppler flow velocities has been described. We report the
      reappearance of a normal end-diastolic flow velocity in a ductus venosus
      temporarily showing reversed end-diastolic flow in a growth-retarded fetus with
      congenital anomalies. This normalization was accompanied by an improvement of the
      CTG, a loss of umbilical vein pulsations, a reappearance of umbilical diastolic
      flow and a progressive return of cerebral and venous blood flow into the 'normal'
      range. Improvement of fetal condition may be the explanation for our observation.

PMID- 11344675
TI  - Acute iliac vein thrombosis in pregnancy treated successfully by streptokinase
      lysis: a case report.
AB  - BACKGROUND: Postthrombotic syndrome is an important late complication after deep
      vein thrombosis in pregnancy. Thrombolytic agents are more efficient in
      preventing this condition but are rarely used in pregnant women. CASE: A 22-year
      old woman at 29 weeks of gestation presented with acute iliac vein thrombosis.
      After application of a heparin bolus, systemic streptokinase lysis was performed.
      Low-dose heparin therapy was continued for the remainder of the, otherwise
      unremarkable, pregnancy. Spontaneous delivery of a healthy girl was without
      complications and thromboprophylaxis with low-molecular heparin was continued.
      CONCLUSION: Thrombolysis in pregnancy is possible and may help to prevent severe
      long-term sequelae of thrombosis in young women. Bleeding is a major risk, which
      must be considered and therapy should only be administered under close
      observation.

PMID- 11344676
TI  - Liquid ventilation in an infant with persistent interstitial pulmonary emphysema.
AB  - We present the case of a full term infant affected by diffuse persistent
      interstitial pulmonary emphysema (PIPE), who was treated with partial liquid
      ventilation (PLV) after the failure of conventional management. PIPE is a lethal
      chronic lung disease of unclear pathogenesis. Clinical history, radiological and
      histological findings confirmed the diagnosis in our patient. PLV applied for 48
      hours resulted in a significant improvement in the infant's respiratory function
      and was not associated with adverse effects. We concluded that PLV could be
      effective in prolonging the survival of infants with PIPE; its application
      represents an effective form of respiratory support in infants with chronic lung
      disease.

PMID- 11344677
TI  - Renal vein thrombosis in a newborn with prothrombotic genetic risk factors.
AB  - Environmental and genetic risk factors interact to cause venous thromboembolism.
      Renal vein thrombosis in the newborn has been frequently associated with "risk
      factors" as catheters, surgery or trauma, but it has also been demonstrated a
      pathogenetic role of genetic prothrombotic risk factors, i.e. activated protein C
      resistance and FV Leiden. The treatment of neonatal venous thrombosis varies
      worldwide and different approaches have been proposed. We present a case of renal
      vein thrombosis in a female newborn with normal plasma levels of protein C,
      protein S and antithrombin III, but with her genotype characterized by the
      presence of three prothrombotic risk factors: factor V Leiden,
      methylentetrahydrofolate reductase and platelet glycoprotein IIIa polymorphisms.
      The treatment with recombinant tissue plasminogen determined complete thrombus
      dissolution.

PMID- 11344678
TI  - Fetal pulse oximetry allows safe continuation of labor in the presence of mild
      moderate non reassuring CTG.

PMID- 11344679
TI  - Malignant disease in pregnancy.
AB  - Cancers in pregnancy are uncommon but do occur with an average frequency of 1 in
      1,000 births. This gives rise to opposing emotional reactions in these women:
      they are happy they are pregnant, but usually devastated when they hear they have
      cancer. The major reasons for suspecting that pregnancy adversely affects the
      clinical course of cancer is the immunologic tolerance that characterizes both
      conditions. It has been pointed out that normal pregnancy and cancer are the only
      two biologic conditions in which the antigenic tissues is tolerated by a
      seemingly intact system. It may be stated that the mechanisms that insure the
      survival of fetus during pregnancy presumably also favors the progress of the
      neoplasia. Management requires individualization with careful thought as whether
      termination is necessary or whether continuing with the pregnancy is possible
      prior to definitive treatment. The physician's aim must be to cure the cancer and
      deliver live, healthy infants. This is one question when a joint decision is
      probably best reached among the obstetrician, surgical and medical oncologists
      and other disciplines. The life-threatening cancer should be managed both for the
      diagnosis and treatment as in the non-pregnant state. An early small cancer gives
      a better prognosis than an advanced cancer. The same holds for the non-pregnant
      patient. The survival in the non-pregnant patient stage for stage is the same as
      for the pregnant patient. However, all too often in the pregnant state the cancer
      is more advanced than in the non-pregnant patient. The disease must be evaluated
      and treated in full light of its exact location in conjunction with an
      understanding of the natural history within the context of the pregnancy with the
      potentially viable unborn infant. Concern that maternal cancer may metastasize to
      the fetus is not justified from a review of the accumulated literature.
      Infrequency of fetal involvement has led to speculation about biologic protective
      mechanisms that may exist for the placenta and the fetus and the role circulatory
      separation in the placenta and immunologic responses of the fetus may play. The
      association of cancer in pregnancy represents a major physiologic process for the
      maintenance of the race and a major pathologic process that accounts for numerous
      deaths. It presents a controlled growth and an uncontrolled growth in the same
      host.

PMID- 11344680
TI  - [Current status of valvular surgery].

PMID- 11344681
TI  - [Mitral valve repair--indication and late results].
AB  - In recent years, mitral valve repair has become more widespread because it
      promises a reduction in both mortality and morbidity compared with valve
      replacement. As the incidence of rheumatic valve disease has declined in Japan,
      degenerative disease has become the most common cause of mitral regurgitation
      (MR), for which repair techniques can be successfully applied. The standard
      repair techniques, including artificial chordal implantation, increase the
      indications for valve repair to up to 95% of patients with MR and improve the
      long-term results. The indications for surgical intervention in patients with MR
      have evolved. Asymptomatic patients are considered for surgery when left
      ventricular function begins to deteriorate or atrial arrhythmias appear.

PMID- 11344682
TI  - [Indications and results of aortic valve repair].
AB  - With the development of prosthetic valves with excellent hemodynamics and
      durability, aortic valve replacement has become the first choice in the surgical
      treatment of valve disease. The significant improvement in mortality rates after
      open-heart surgery has resulted in a demand not only for good hemodynamics but
      also for a better postoperative quality of life. Because mechanical prosthetic
      valves are associated with postoperative complications and patients receiving
      them must remain on anticoagulant therapy for life, and bioprosthetic valves are
      not sufficiently durable, valve repair techniques are being reevaluated and new
      ones developed. The indications for valve repair have been extended in mitral
      valve disease due to the decreased incidence of rheumatic valve disease and
      increase in degenerative tissue valve disease. Reports indicate that both acute
      and long-term postoperative results are superior after valve repair compared with
      valve replacement. Similarly, although some reports on the results of aortic
      valve repair indicate that the standard techniques do not yield satisfactory long
      term results, others suggest that newer techniques may improve the results in
      both the acute and long-term, chronic phase.

PMID- 11344683
TI  - [Late results after mitral valve replacement].
AB  - Recent reports on mitral valve replacement (MVR) are reviewed and topics in this
      field are discussed. In addition to the widely used St. Jude Medical (SJM) valve,
      five other bileaflet prosthetic valves are now commercially available in Japan.
      The clinical performance of the new type of bileaflet valve appears similar to
      that of the SJM valve. The lincarized rate of thromboembolism occurrence for any
      bileaflet valve is less than a few %/patient-year in most reports. The actuarial
      and actual freedom from structural valve deterioration(SVD) 14 years after MVR
      with the Carpentier-Edwards pericardial valve was reported to be 69% and 83%,
      respectively, while the actuarial freedom from SVD 12 years after MVR with the
      Hancock II porcine valve was 82%. In Japan, the rate of use of bioprostheses is
      approximately 10%. When selecting a prosthetic valve, informed patient consent
      based on the most recent data is recommended. Numerous reports have been
      published on chorda-preserving MVR indicating the superiority of this technique
      over conventional MVR in terms of left ventricular function. There are several
      options for prescribing the chordae and for artificial chordae reconstruction.
      Improved methods for sparing the chordae are being investigated in animal models.

PMID- 11344684
TI  - [Long-term results of aortic valve replacement].
AB  - In order to improve the quality of life after cardiac valvular surgery, new
      procedures and new prostheses have been developed in the past decade. Surgeons
      have many alternatives for the individual patient. However, some may only
      represent a trend without any clinical advantage, some may increase the surgical
      risk, and some may have limited indications for specific types of heart disease.
      Therefore the selection of the procedure and prosthesis is very important. The
      new mechanical valves have a thinner ring and cuff, providing a larger orifice
      for patients with a small aortic annulus, and enlargement procedures are now
      rarely required. Second-generation biological valves have been used for more than
      15 years. In the aortic position in elderly patients, the rate of freedom from
      structural deterioration is over 90% at 15 years. The stentless valve is the most
      notable newer prosthesis and has significant hemodynamic advantages, associated
      with good myocardial remodeling.

PMID- 11344685
TI  - [Indications for and results of cryopreserved homograft valve replacement].
AB  - The cryopreserved aortic homograft valve is one of the most reliable of the
      stentless biological prosthesis if implanted properly. Due to the limited
      availability of homograft valves in Japan, the indications for their use are
      different from those in other countries. The first indication is active infective
      endocarditis in the aortic valve position, especially infection surrounding
      artificial implants. Another indication is for reconstruction of the right
      ventricular outflow tract during pulmonary autografting. Finally, aortic valve
      replacement in young women of childbearing age who wish become pregnant is an
      accepted indication. Since 1992, cryopreserved homograft valves have been used in
      Japan, and the number of surgeries performed with them has gradually increased.
      While efforts have been made to expand the homograft bank system in some areas,
      the supply remains insufficient. Because the demand for homografts is high, it is
      extremely important to establish a nationwide tissue bank system as soon as
      possible.

PMID- 11344686
TI  - [Indications for and clinical outcome of the Ross procedure: a review].
AB  - The Ross procedure has been used increasingly to treat aortic valve disease in
      children and young adults. The primary indication for the Ross procedure is to
      provide a permanent valve replacement in children with congenital aortic
      stenosis. More recently, it has been extended to young adults with a bicuspid
      aortic valve and small aortic annulus, especially women wishing to have children.
      Other possible indications include complex left ventricular outflow obstructive
      disease, native or prosthetic valve endocarditis, and adult aortic insufficiency
      with a dilated aortic annulus. Conversely, Marfan syndrome is considered to an
      absolute contraindication, and this procedure should be used with caution in
      patients with rheumatic valve disease and a dysplastic dilated aortic root
      because of the higher associated incidence of autograft dysfunction. The
      technique of total aortic root replacement has become the preferred method of
      autograft implantation, because it carries the lowest risk of pulmonary autograft
      failure. In patients with marked graft-host size mismatch, either concomitant
      aortic annulus reduction and fixation or aortic annulus enlargement (i.e., the
      Ross-Konno procedure) should be performed. The Ross Procedure International
      Registry data document that in the modern era (post-1986) the early and late
      mortality rate is 2.5% and 1%, respectively. Excellent long-term results have
      been reported, and the benefits of this procedure include optimal hemodynamics,
      low risk of endocarditis, resistance to infection in patients with active
      endocarditis, and nonthrombogeneicity and therefore few anticoagulation-related
      complications. The Ross procedure can be performed with acceptable early and mid
      term mortality and excellent autograft durability. Further long-term follow-up
      will confirm the role of this procedure in patients with various types of aortic
      valve disease.

PMID- 11344687
TI  - [Surgical strategy for tricuspid valve disease].
AB  - The most common cause of tricuspid valve dysfunction is functional tricuspid
      regurgitation (TR) secondary to mitral valve disease. Annuloplasty is feasible in
      most patients with functional TR, and valve repair can also be performed in most
      patients with tricuspid valve dysfunction of other etiologies. Valve replacement
      is considered to be indicated only for those patients whose tricuspid valves have
      severe organic change or have been damaged by infective endocarditis. Although
      good long-term results of tricuspid valve replacement using bioprostheses have
      been reported, a bileaflet mechanical prosthesis may be an acceptable alternative
      in those patients who undergo concomitant valve replacement with a mechanical
      prosthesis in the mitral or aortic position or who may have persisting pulmonary
      hypertension after surgery.

PMID- 11344688
TI  - [The surgical treatment of congenital valve disease].
AB  - The clinical results after surgical treatment of congenital valve disease have
      improved due to the use of several recently developed techniques. The replacement
      of tendinous cords using E-PTFE sutures has allowed the indications for the
      repair of mitral valve prolapse to be extended. The Ross procedure has made it
      possible to replace the aortic valve associated with small aortic annulus.
      However, replacement with a prosthetic valve remains the only option if repair is
      not possible or fails. Prosthetic valve replacement in the pediatric age-group
      remains challenging in patients with a small valve annulus. A number of
      techniques can be employed in such cases, including enlargement of the aortic
      annulus and translocation of the prosthetic valve in the left atrium, although
      there are limits on the size of the prosthesis. Further improvement of surgical
      techniques is necessary, along with the development of prosthetic valves using
      more nearly physiological materials.

PMID- 11344689
TI  - [Combined surgery for valvular and ischemic heart disease].
AB  - Combined coronary artery bypass (CAB) and valve surgery is one of the most
      challenging surgical procedures, but the operative results have improved over the
      years. We discuss several important points in combined surgery. The first point
      is cardioplegia, which should be perfect in such complex operations. Sufficient
      antegrade cold blood cardioplegia should be used in combined CAB and mitral valve
      surgery. Continuous retrograde cardioplegia is required in CAB and aortic valve
      surgery. The second point is the prosthesis and grafts. A mechanical prosthesis
      and arterial grafts should be used in younger patients, while a bioprosthesis and
      vein grafts with a left internal thoracic artery graft should be used in older
      ones. Finally, the choice of valve repair or replacement must be considered in
      mitral surgery with CAB. Valve repair is the choice in patients with mitral
      prolapse due to chordal rupture, because a perfect repair can be achieved using a
      well-known procedure. In cases in which repair appears difficult, replacement
      must be carried out as soon as possible. In mitral valve replacement the
      continuity between the papillary muscles and the mitral ring must be preserved
      for good left ventricular performance.

PMID- 11344690
TI  - [Clinical experiences in the Liver Unit, the Queen Elizabeth Hospital, United
      Kingdom].
AB  - The present status of liver transplantation in th UK is described based on our
      clinical experience in the Liver Unit, Queen Elizabeth Hospital. In 1999, there
      were 161 cadaveric liver transplantations in the Liver Unit. The shortage of
      suitable donors for transplantation is widely recognized and is a worldwide
      problem. In order to solve this problem, "marginal donors" who would usually be
      refused on medical grounds have been used, and split-liver transplantation
      procedures have been developed in the Liver Unit.

PMID- 11344691
TI  - [Three cases of multiseptate gallbladder].
AB  - Multiseptate gallbladder is an extremely rare congenital anomaly. We report three
      cases of this clinical entity. The third patient, a 70-year-old male who was
      asymptomatic with this condition, also had a gallbladder carcinoma. The three
      surgically removed gallbladders had multiple thin septa with a honeycomb
      appearance. Histologically, the septa contained a muscular layer that was
      continuous with the gallbladder wall. Furthermore, in the third patient, mucinous
      cystadenoma with focal carcinomatous change in the epithelium was observed. To
      our knowledge, this is the first description of a multiseptate gallbladder with
      carcinoma.

PMID- 11344692
TI  - [Fibrohistiocytic sarcoma of the kidney (borderline malignancy)].
AB  - We described a case of 45 year old woman with left kidney tumour. In the
      pathological examination it appeared asa very seldom neoplasm--fibriohistiocytoma
      sarcomatosum. This lesion was accidentally diagnosed in ultrasound evaluation due
      to myomatous uterus observation in gynaecological hospital. There were no signs
      or symptoms of kidney tumour disease.

PMID- 11344693
TI  - [Deafness, as a complication of Pseudomonas aeruginosa septicemia in a 9-year old
      boy with acute lymphoblastic leukemia].
AB  - We described natural history of Pseudomonas aeruginosa septicemia in 9 year old
      boy, who was treated for acute lymphoblastic leukemia (ALL). After 14 day
      treatment of ALL the following signs and symptoms occurred: fever, earache with
      otorhoea, deafness, bilateral peripheral paralysis of n. VII, erythema,
      pneumonia, paralytic ileus. After 4 weeks of antimicrobial and supportive
      therapy, in the 10th week of chemotherapy, he achieved haematological remission.
      During continuation therapy, two-stage bilateral myringoplasty was performed. At
      present the maintenance therapy is continued, and in the future hearing aid and
      cochlear implant, will be applied.

PMID- 11344694
TI  - [Evaluation of vitamin B6 and calcium pantothenate effectiveness on hair growth
      from clinical and trichographic aspects for treatment of diffuse alopecia in
      women].
AB  - The aim of the study was the clinical and trichological examination (trichogram
      and hair loss evaluation) conducted comparatively before and after the treatment
      in 46 women between pubescence and 30 years of age who had symptoms of diffuse
      alopecia. Calcium pantothenate was administered twice a day orally in doses 100
      mg for 4-5 months. Vitamin B6 was injected every day (i ampoule intramusculary)
      for the period of 20 to 30 days and repeated again after 6 month. On the basis of
      clinical and trichological studies it was revealed that vitamin B6 administered
      parenterally for a period of several weeks induces improvement in the hair
      condition in a number of women and it reduces the hair loss especially in
      alopecia of telogenic patomechanism. Whereas calcium pantothenate in feminine
      diffuse alopecia did not show clearly the positive effect.

PMID- 11344695
TI  - [A case of bilateral, simultaneous breast amputation for cancer palpated in the
      left breast and undiagnosed in the right breast with different histologic
      classifications].
AB  - The paper presents the case of bilateral simultaneous breast amputation due to
      different histological classification cancer. The right breast tumor was non
      palpable.

PMID- 11344696
TI  - [Occupational penicillin allergy as an example of chronic recurring anaphylaxis].
AB  - A case of anaphylactic shock which appeared in a nurse working at surgery room
      for many years, was described. The nurse was examined due to the anaphylactic
      attack at work (paroxysmal, idiopathic anaphylaxis). Among many factors the first
      of all occupational ones (exposure to disinfectants, latex and penicillin) were
      taken into consideration. Two minutes after the intradermal application of 2
      units of crystalline penicillin the symptoms of anaphylaxis (including the shock)
      occurred. The problems of penicillin allergy in the aspect of skin tests, which
      make use of this antibiotic, were also described in the paper.

PMID- 11344697
TI  - [Antibodies against Borrelia afzelli in patients with an early stage of Lyme
      disease].
AB  - The aim of the study was evaluation of specific immune response against Borrelia
      afzelii in patients with erythema migrans, as a sign of an early stage of Lyme
      borreliosis. The study was performed in 42 patients, residents of Podlasie
      province, who were initially evaluated by indirect immunofluorescence assay as a
      seropositive for Borrelia burgdorferi sensu lato. Antibodies against particular
      antigens of B. afzelii were demonstrated using a Western-blot technique.
      Evaluation of results showed the most frequent prevalence of antibodies against
      41 kDa antigen in majority of patients, which were predominantly of IgM class in
      patients with short-lasting lesions, and IgG class in patients with long-lasting
      lesions. Results of IgM blots were recognized as a positive in 26 patients, and
      IgG blots in 22 patients. Positive result in at least one class of antibodies was
      noted in 34 patients (81%), and in both classes in 14 (33%). IgM antibodies
      against 21 kDa antigen, and IgG antibodies against 43 kDa antigen were two fold
      more frequent in patients with short-lasting lesions. These results confirm the
      diagnostic usefulness of determination of antibodies against B. afzelii antigens
      in Poland. The most important for an early diagnosis can be simultaneous
      demonstration of IgM antibodies against 21 and 41 kDa antigens.

PMID- 11344698
TI  - [Evaluation of an atypical clinical presentation for pneumonia caused by
      Mycoplasma pneumoniae and Chlamydia sp in children].
AB  - Mycoplasma pneumoniae and Chlamydia sp. frequently cause atypical pneumonia in
      children. The study aim was the analysis of clinical picture of pneumonia caused
      by Mycoplasma pneumoniae and Chlamydia sp. in 278 children treated in the period
      of 1985-1998 in the IInd Clinic of Pediatrics and Gastroenterology, Medical
      Academy of Wroclaw. The influence of etiological factor and age of children for
      the clinical picture of the disease was estimated. The most characteristic
      clinical symptom of the atypical pneumonia in children was "staccato" cough
      observed in 89.9% of children. More severe course of the mycoplasmal pneumonia in
      comparison with that of Chlamydia origin was demonstrated. The most severe course
      of pneumonia was observed in infants. The afebrile course of the disease was
      observed in the group of Chlamydia pneumonia (in 26.3% of infants, 40% of
      children aged 1-6 years and 54.8% of children aged 7-15 years). None of children
      with mycoplasmal pneumonia had an afebrile course of the disease. The most
      characteristic radiological picture in children with atypical pneumonia were
      diffused, symmetrical interstitial inflammatory changes of the lungs. In the
      group of children with mycoplasmal pneumonia in over 50% of cases the enlargement
      of lymph nodes of the lungs hili were observed.

PMID- 11344699
TI  - [The effect of prokinetic treatment and eradication of Helicobacter pylori on
      gastric emptying and symptoms of functional dyspepsia].
AB  - The aim of the study was to estimate clinical symptoms and gastric emptying in
      functional dyspepsia (f.d.) before and after treatment. METHODS: 40 patients were
      examined. Control group consisted of 10 healthy volunteers. The severity of
      symptoms was estimated in 0-3 score. Gastric emptying was measured with
      radionuclide method. Examinations were performed prior and after treatment with
      famotidine (group I), cisaprid + famotidine (group II), cisaprid (group III),
      eradication of H.p. (group IV). RESULTS: Significantly delayed gastric emptying
      was observed in patients with f.d. Severity of symptoms score was significantly
      reduced after treatment, and was: group. I 13.8-11.2, group II. 14.8-8.8, group
      III 13.7-6.9, group IV 13.3-9.0. Gastric emptying was improved after treatment in
      groups: II 64.3-45.5 and III 65.1-46.7 respectively. In groups I and IV there was
      a minor nonsignificant change in gastric emptying. CONCLUSIONS: 1. Gastric
      emptying is significantly delayed in patients with f.d. 2. Prokinetic therapy
      with cisapride results in the improvement of gastric emptying together with
      alleviation of clinical symptoms of f.d. 3. Antisecretory treatment with
      famotidine and eradication of Helicobacter pylori do not effect gastric emptying,
      but exerts positive clinical response.

PMID- 11344700
TI  - [Anatomic abnormalities within upper airways in patients with obstructive sleep
      apnea syndrome].
AB  - In order to determine a proper method of the treatment of Obstructive Sleep Apnea
      Syndrome (OSAS) it is essential to demonstrate anatomical abnormalities of upper
      airways. In this study we would like to estimate how often these anatomical
      abnormalities occur and what is their influence on OSAS severity. 113 patients
      underwent laryngological examination, the nasal structure, palate and pharynx
      were evaluated. The anatomical abnormalities of upper airways were found in 86%
      patients. The most frequent abnormalities found were nasal disorders, however
      they were not correlated with OSAS severity. Anatomical abnormalities in more
      than one level of upper airways were found in 50% of the patients and in those
      patients OSAS symptoms were the most severe. This may explain why the most
      frequently performed operations in OSAS patients are not very effective.

PMID- 11344701
TI  - [Amiodarone for long term treatment of arrhythmia in children].
AB  - Amiodarone was used in 37 pediatric subjects aging 1 day--16 years. Very high
      efficiency of long-term treatment (mean 8 months) was found in the cases of
      supraventricular as well as ventricular tachyarrhythmias (paroxysmal and
      nonparoxysmal) including complex life-threatening ones. The treatment was not
      effective only in three subjects. In the other cases normal heart rhythm was
      achieved or duration time and number of tachycardia attacks was reduced. The
      class of arrhythmia improved. It was often recommended to use amiodarone together
      with digitalis preparation in order to obtain its antiarrhythmic activity. Our
      usual amiodarone dose was 10-20 mg/kg of body mass/24 h intravenously (in order
      to interrupt the attack) or 10 mg/kg/24 h per os in saturation period. Then the
      daily dose was reduced to the mean equal 5 mg/kg. Amiodarone side effects were
      observed in rather high percentage of subjects (24%) during long-term treatment.
      There were abnormal laboratory tests or laboratory and clinical abnormalities of
      thyroid function observed in 3 cases. In 4 other ones amiodarone deposits in
      cornea were found. They disappeared in 2 cases after drug dose reduction. In 1
      child the symptoms of lung fibrosis and in the other one of sunshine
      hypersensitivity were observed. Thus, because of side effects treatment had to be
      interrupted in 7 cases (19%). It is concluded that amiodarone is exceptionally
      effective antiarrhythmic drug, very useful also in the youngest pediatric
      patients. On the other hand it is concluded, that the treated subjects must
      remain under careful medical control because of high rate of amiodarone side
      effects.

PMID- 11344702
TI  - [Gallbladder carcinoma detected accidently by histopathologic examination].
AB  - A group of 14 patients, in whom gallbladder carcinoma was detected accidentally
      in histopathological examinations, after cholecystectomy due to cholelithiasis,
      was analyzed, comparing the macroscopic evaluation of excised gallbladders with
      microscopic examinations. The only common macroscopic feature was thickening of
      gallbladders' walls, which is insufficient to suspect carcinoma in preoperative
      and operative examinations.

PMID- 11344703
TI  - [The course of post-streptococcal glomerulonephritis depending on methods of
      treatment for the preceding respiratory tract infection].
AB  - The aim of our work was to assess the course of post-streptococcal
      glomerulonephritis (APSGN) in children according to the way of preceding
      respiratory tract infection treatment. The examinations were carried out in a
      group of 26 children aged 5-15 years, who were divided into two subgroups: I--12
      children, who did not receive antibacterial treatment, and II--14 children who
      were shortly treated with different antibiotics (3-5 days). All the children had
      full symptomatic picture of post-streptococcal glomerulonephritis with
      haematuria, oedemas, hypertension and hypocomplementemia. The etiology was
      diagnosed retrospectively during observation of ASO titer dynamics and
      additionally in 18 after finding pathogenic Streptococcus strains in pharyngeal
      swab. The differences in the course of illness was shown only during first weeks.
      In children from the group I the course of acute APSGN was a little more serious,
      because haematuria, proteinuria and hypertension were observed longer. Symptoms
      of nephrotic syndrome were observed in two children, acute renal insufficiency in
      two children, and one with hypertensive encephalopathy. After 3 and 12 months no
      children had pathological signs. Erythrocyturia was observed in 19 of 26 children
      after 3 months and in 10 of 26 children after 12 months after illness with
      similar frequency in both groups. In 5 children with proteinuria renal biopsy
      showed mesangialis proliferative glomerulonephritis--1st degree. CONCLUSION: All
      observed children with APSGN were not cured properly during the respiratory tract
      infection preceding the disease, however even short antibacterial treatment
      caused the moderation of symptoms.

PMID- 11344704
TI  - [Borreliosis--"the big imitator"--difficulties in diagnosis and differentiation
      of diseases].
AB  - Difficulties in the diagnostics and differential diagnosis of borreliosis were
      presented. The ways of infection, epidemiology as well as clinical picture were
      described. The pathogenesis of arthritis accompanying borreliosis and its place
      in the group of rheumatic diseases are mentioned in the article.

PMID- 11344705
TI  - [Mycosis in otolaryngology].
AB  - Authors present the most common systemic and opportunistic mycotic infections in
      otolaryngology. Morphological structure, development cycle and low requirements
      give possibilities to spread the disease. Mycotic infections can cause different
      disease entities even with the same fungal pathogen.

PMID- 11344706
TI  - [Symptoms and pathomechanism of changes in the digestive system during the course
      of systemic lupus erythematosus].
AB  - In this work, authors make an attempt to review and systematize digestive system
      symptoms and pathomechanism of changes in the course of systemic lupus
      erythematosus (SLE). They also point out the increasing role of visual methods in
      the diagnostics of connective tissue diseases. It should be noted that though
      Osler described first visceral symptoms of systemic lupus erythematosus in 1895,
      this topic has gained little interest in literature.

PMID- 11344707
TI  - [Some stomatologic health problems in elderly persons].
AB  - The year 1999 was acclaimed The Year of Ripe Age by WHO. On account of this,
      attention should be paid to problems related to changes within the oral cavity
      tissues, mandibular and circummandibular bones, which progress together with the
      process of ageing. These changes may be due to physiological involutional
      processes or due to increasing tendencies towards various pathological changes.
      In general opinion the loss of teeth, which do not need to be treated, is the end
      of basic diseases and dental problems only concern prosthetic supplements.
      Obligatory, periodic dental examinations are not imposed on the population of old
      people. Thus, the only possibility of early diagnosis of morbid processes within
      tissue structures of the oral cavity, is general examination including a detailed
      inspection of the oral cavity, even if the patient does not complain about any
      indisposition.

PMID- 11344708
TI  - [Burden of caregivers caring for persons with dementia].
AB  - Alzheimer's disease (AD) and other dementias are common disorders in the elderly.
      Most AD patients are cared for at home by family members. Caregiving stress often
      leads to problems in care givers' mental and physical health. Certain factors
      predict caregivers' distress, such as the presence of patient behavioral
      problems, the nature of the caregivers' social support and ability to cope with
      difficult situations. The term "caregiver burden" is used to refer to the
      physical, psychological or emotional, social and financial problems that can be
      experienced by family members caring for impaired older adults.

PMID- 11344709
TI  - [Surgery for idiopathic macular hole in stage III/IV: is long-acting gas
      tamponade indispensable?].
AB  - In order to test the hypothesis that in stage III/IV idiopathic macular hole
      surgery, a short-acting gas tamponade with 40% SF6 and postoperative positioning
      for 7 days is anatomically and functionally as successful as a long-acting gas
      tamponade with 14% C3F8 and a postoperative positioning for 14 days, 2
      consecutive series of eyes operated on with the same technique, excepted for the
      gas tamponade used, are compared. The anatomical and functional success rates are
      not statistically different between both groups.

PMID- 11344710
TI  - Review of the current state research into the management of age-related macular
      degeneration (AMD)(1).

PMID- 11344711
TI  - [Correlation between Goldmann and non-contact tonometry based on corneal
      thickness].
AB  - In this transversal study, we measure the intra ocular pressure by means of the
      Goldmann tonometer and a Non-Contact tonometer along with the central cornea
      thickness in 136 eyes of 73 patients. The statistical analysis of the collected
      data doesn't allow us to establish a correlation between the variation of the
      corneal thickness and the difference between the Goldmann tonometer and Non
      Contact tonometer measures. The relative precision of the Non-Contact tonometer
      compared with the Goldmann tonometer doesn't seem influenced by the central
      cornea thickness.

PMID- 11344712
TI  - Different strategies for Humphrey automated perimetry: FASTPAC, SITA standard and
      SITA fast in normal subjects and glaucoma patients.
AB  - PURPOSE: To evaluate the influence on examination time and test quality of the
      recently introduced SITA strategies of the Humphrey Field Analyzer. METHODS: The
      sample consisted of 41 subjects (19 normal subjects and 22 glaucoma patients),
      all experienced in automated perimetry, ranging in age from 24 to 83 years. One
      eye of each patient was examined with the HC30-2 program using the FASTPAC (FP)
      and SITA Standard (SS) or SITA Fast (SF) strategy on the same day, in random
      order. Examination time was evaluated as a function of the strategy. To evaluate
      the test quality both regional and global visual field parameters were analyzed.
      Global parameters included mean deviation (MD) and pattern standard deviation
      (PSD). Regional parameters (mean and maximum loss) were calculated to estimate
      the extent and the depth of localized visual field defects. For this purpose each
      visual field was divided in 4 quadrants and in 10 clusters as defined in the
      glaucoma hemifield test. RESULTS: 1. There is a considerable test time reduction
      from FASTPAC over SITA Standard to SITA Fast for comparable MD and PSD values. On
      average, the SITA Fast test duration is half that of the FASTPAC procedure. For
      each strategy, the test duration increases for increasing visual field loss. 2.
      Between all three strategies, there is a good correlation for the global indices
      (MD, PSD) 3. For the regional indices (mean loss, maximum loss) the same high
      correlation exists. CONCLUSION: The SITA strategy causes a significant test time
      reduction without decreasing the test quality.

PMID- 11344713
TI  - Patterns of intraocular inflammation in children.
AB  - AIM: To report on the causes of uveitis in children and young adults and their
      effects on visual functions. MATERIALS AND METHODS: Two hundred and seventy six
      patients, 18 years old or younger, with uveitis were included in this study. The
      intraocular inflammation (uveitis) was classified according to anatomical site of
      ocular involvement and the most probable etiological factor. The final diagnosis
      was based on clinical manifestations and the results of specific laboratory
      investigations. RESULTS: Bilateral intraocular inflammation was observed in 70.3%
      of the cases and 29.7% had either the left or the right eye involved. The
      symptomatology was relatively mild in most cases despite the fact that the visual
      acuity was markedly affected. An associated systemic disease was detected in
      40.2% of the cases classified as non-infectious. Of this group, juvenile
      rheumatoid arthritis was the most common single systemic associated cause
      detected in 41 children. In 110 children (59.8%), the uveitis was strictly
      confined to the eyes with 70 of these (25.4% of the total group) classified as
      idiopathic. Parasites were the most common infectious-associated cause for the
      uveitis followed by viruses and bacteria. CONCLUSION: Uveitis is highly prevalent
      among children. In children, symptomatology of the intraocular inflammation may
      be very mild. However, visual acuity is markedly reduced leading to amblyopia in
      the young children. Early detection and treatment is therefore of utmost
      importance.

PMID- 11344714
TI  - [Intermediate uveitis].
AB  - Intermediate uveitis is a chronic and insidious disease. Children and young
      adults are preferentially affected. Vision loss and floaters are commonly
      reported in a quiet eye. The inflammation predominates in the vitreous and some
      characteristic peripheral exsudates may be observed. Intermediate uveitis is
      generally idiopathic but may sometimes be associated with a systemic disease that
      must be researched and treated. The treatment of the idiopathic form is only
      necessary in case of complications and will consist in corticosteroids eventually
      combined with immunosuppressive drugs. Surgery (cryotherapy, vitrectomy) will be
      reserved for complications non responding to medical therapy.

PMID- 11344715
TI  - [Treatment of uveitis with immunosuppressives: antimetabolites and alkylating
      agents].
AB  - Oral corticosteroids remain the main therapeutical choice in patients with
      uveitis not responding to topical treatment, however their chronic use can be
      very toxic, especially for bones (osteoporosis or growth retardation).
      Immunosuppresive agents are used as corticosteroid sparing agents and/or as
      agents able to control refractory uveitis in sight threatening uveitis.
      Cyclosporin A is very efficacious but is nephrotoxic, in particular in old
      people. Methotrexate is well tolerated in young people, is not carcinogenic but
      not very active. Azathioprine is well tolerated but it's carcinogenic effect and
      its delayed action are helpful in chronic uveitis of old women. Cyclophosphamide
      and intravenous steroids are helpful for emergencies. Chlorambucil is toxic and
      carcinogenic but might lead to an increased rate of remission and might be useful
      as a short treatment. In any case, a careful and regular follow-up in
      collaboration with a competent internist is mandatory.

PMID- 11344716
TI  - [Chronic endophthalmitis].
AB  - Chronic endophthalmitis are intraocular infections, characterized by late onset
      and prolonged evolution. They are either of exogenous or endogenous origin and
      may be related to the penetration of "fastidious bacteria", mycoses or viruses.
      Diagnosis is based on specific techniques, including direct examination
      peroperatively, prolonged cultures on special medium and electron microscopic
      analysis. Treatment often combines diagnostic/therapeutic vitrectomy and
      intraocular injection of antibiotics. Their evolution is usually made of
      successive reactivations and explanting of the artificial lens is often necessary
      for a definitive remission in pseudophakic patients.

PMID- 11344717
TI  - White spots syndromes.
AB  - The different types of white spots occurring in the fundus are analysed. A. Acute
      white spots, vanishing later on. 1. Multiple Evanescent White Dot Syndrome. 2.
      Cat scratch disease. 3. AIDS microangiopathy. 4. Cotton-wool spots. 5. Acute
      vitelliform maculopathy. B. Acute white spots with coalescence and diffuse
      scarring. 1. Acute posterior multifocal placoid pigment epitheliopathy. 2.
      Serpiginous choroiditis (geographic choroiditis). 3. Herpes retinitis. C. Acute
      white spots becoming white scars with variable pigmentation. 1. Multifocal
      choroiditis--classical form. 1a. Punctate inner choroidopathy. 1b. Diffuse
      subretinal fibrosis. 2. Toxoplasmic retinochoroiditis. 3. Tuberculous
      chorioretinitis. 4. Syphilitic chorioretinitis. 5. Lyme disease. 6. Sarcoidosis.
      7. Sympathetic ophthalmia. 8. Vogt-Koyanagi-Harada disease. 9. Bacterial
      retinochoroiditis. 10. Fungal retinochoroiditis--Candida. 11. Pneumocystis
      carinii choroiditis. D. Late white spots with or without initial white-orange
      spots. Birdshot chorioretinitis.

PMID- 11344718
TI  - Unusual retinal vasculitis in a patient with protein S deficiency and systemic
      toxoplasmosis: a case report.
AB  - A 28-year old female patient presented with unilateral dropped visual acuity and
      a central scotoma. Fundus examination and a fluorescein angiogram were suggestive
      for central retinal vein prethrombosis. Further tests revealed an isolated
      protein S deficiency for which oral anticoagulation therapy was initiated. Six
      months later she presented with new symptoms of a right retrobulbar pain on
      ocular movements. The retinal vessels had normalized with improved visual acuity.
      Re-evaluation of the fluorescein angiogram taken six months earlier showed an
      image compatible with unilateral vasculitis. During this six month period
      persisting high levels of IgG and IgM antibodies against Toxoplasma were observed
      while no signs of other active infection could be found. This report illustrates
      that in cases of prethrombosis with vasculitis in a young patient, a full medical
      examination and a thorough investigation of infectious diseases are warranted.

PMID- 11344719
TI  - [Intra-ocular non-Hodgkin's lymphoma. Diagnostic aspects].
AB  - Intraocular non-Hodgkin lymphoma often masquerades a chronic uveitis, which does
      however not respond to local and/or systemic immunosuppressive treatment. The
      anterior segment signs are usually discrete, although a hypopion may appear
      during evolution. The vitreous is often markedly involved. The chorioretinal
      lesions are variable in aspect. Subretinal infiltrates or solid retinal pigment
      epithelial detachments are the most characteristic fundus signs of the disease.
      Other fundus signs may be present, such as retinal vascular occlusions,
      perivasculitis, macular oedema, optic disc oedema or ischaemic optic neuropathy.
      The diagnosis is based on histological or cytological examination of anterior
      chamber material in case of hypopion, or more frequently from vitrectomy
      specimens or from direct biopsy of suspected fundus lesions. Polymerase chain
      reaction and flow cytometry can be extremely helpful in the diagnosis of
      intraocular lymphoma when the cytology is not conclusive.

PMID- 11344720
TI  - Management of non Hodgkin's intraocular lymphoma with intravitreal methotrexate.
AB  - Intraocular non Hodgkin's lymphoma has traditionally been treated with
      radiotherapy or systemic chemotherapeutic agents. Unfortunately, radiotherapy
      rarely leads to a long term remission, and can only be safely administered once.
      Systemic chemotherapy has limited intraocular penetration. Intravitreal
      administered methotrexate is highly effective at inducing remission and is well
      tolerated. A case report is presented of a recurrent intraocular lymphoma
      following radiotherapy and systemic chemotherapy which responded to a combination
      of intravitreal methotrexate and dexamethasone. A response was seen within three
      weeks of treatment initiation. Toxicity was limited to the progression of a pre
      existing cataract. Review of the literature shows that intravitreal methotrexate
      is well tolerated, with few acute complications. However, with monotherapy, local
      recurrences have been observed.

PMID- 11344721
TI  - [Psychomotor development in the blind infant].
AB  - The blind from birth has a slower psychomotor development than the normal child
      because he must palliate the deficiency of visual information by the development
      of suppletory senses and integrate these information to the structuration of
      environment. An early assistance by a multidisciplinary team with an important
      participation of the family will however permit a harmonious development.

PMID- 11344722
TI  - Can West Nile virus outbreaks be controlled?

PMID- 11344723
TI  - The effect of a new rigid gas-permeable contact lens design on lactic
      dehydrogenase activity in rabbit tears.
AB  - BACKGROUND: Most corneal damage induced by contact lenses is due to interference
      with corneal oxygenation. OBJECTIVE: To investigate the effect on the rabbit
      cornea of a rigid gas-permeable contact lens with a newly designed periphery.
      METHOD: We fitted New Zealand white rabbits (n = 12) with RGP contact lenses that
      were identical in all respects except for the design of the periphery. In each
      animal, one contact lens had an innovative periphery consisting of a microscopic
      diffractive relief lathed on the back surface; the other contact lens was of a
      conventional design. The lenses were worn continuously for 7 days. During this
      experimental period and for 1 additional week we assessed the corneal damage by
      daily testing lactic dehydrogenase activity in the tears. RESULTS: On the last
      day of the experimental week and the first 3 days of the healing period, mean
      tear LDH activity was significantly lower in the eyes with the new contact lens
      design than in eyes with the conventional lenses. CONCLUSIONS: The novel
      periphery design reduces corneal damage resulting from contact lens wear, as
      reflected by LDH levels in the tears. The new design probably facilitates the
      flow and exchange of tears under the contact lens, resulting in improved
      metabolism of the cornea. These findings may also prove applicable to soft
      contact lenses.

PMID- 11344724
TI  - Compliance with influenza vaccination in Israel in two successive winters,
      1998/1999 and 1999/2000.
AB  - BACKGROUND: Although influenza is usually a mild self-limiting disease it can
      cause serious complications in high risk groups. The economic costs of influenza
      are large due to the burden on the health system and absenteeism from work. There
      is evidence that the vaccine is underused in groups targeted for vaccination.
      OBJECTIVES: To estimate: a) the compliance rate with the influenza, vaccination
      in Israel during the winter seasons of 1998/1999 and 1999/2000, b) the role of
      health care personnel and the media in influencing compliance, and c) the reasons
      for lack of compliance in the elderly. METHODS: Two national population-based
      random telephone surveys of 1,500 households were performed during October 1999
      and January 2000 to survey influenza vaccination compliance prior to the winters
      of 1998/1999 and 1999/2000 respectively. Each survey was performed during four
      successive evenings. The response rate was 78.1% for the first survey and 79.1%
      for the second. RESULTS: Vaccination compliance was similar in both surveys. The
      average rate of vaccination was 6% for the population under 65 years and 50% for
      the population of 65 years and above. The overall vaccination rate was around
      10%. The family physician was the main authority to recommend the vaccination,
      followed by the community nurse. Absence of recommendation and lack of faith in
      the efficacy of the vaccine were the main reasons for noncompliance. CONCLUSIONS:
      Compliance rates with influenza vaccine in targeted groups in Israel remain
      relatively low. Health care personnel should be more involved in promoting the
      vaccine.

PMID- 11344725
TI  - Horizontal equity in medical care: a study of the Israeli public's views.
AB  - BACKGROUND: With market failures characterizing the health care sector, societies
      are continuously searching for ways to achieve an efficient and fair allocation
      of resources. A natural source of opinion on the desired allocation of health
      resources is the public. In fact, several governments have recently involved the
      general public in decisions about resource allocation in their health systems.
      OBJECTIVES: To investigate the views of the Israeli Jewish public aged 45-75 on
      horizontal equity in medical care; specifically, the characteristics (including a
      lottery) for determining which of two individuals with similar medical need
      should be treated first, against a background of limited resources. METHODS: A
      sample of 2,030 individuals was chosen to represent a population of about 800,000
      urban Jewish Israelis aged 45-75. Data were collected in face-to-face full sit
      down interviews by trained interviewers between October 1993 and February 1994.
      RESULTS: The three most preferred prioritizers were chances of recovery, number
      of dependants, and young age. Random prioritization was preferred by only 8% of
      the population. Age, level of education and religiosity were the main
      characteristics associated with the choice. CONCLUSIONS: The Israeli adult public
      does not favor strict horizontal equity in health care. As in other social
      programs, "equals" were defined in a multi-criteria manner, based on both medical
      need and other personal characteristics. The preferred prioritizers seem to
      reflect universal tastes and cast doubt on the traditional distinction between
      efficiency and equity and between horizontal and vertical equity when applied to
      health care.

PMID- 11344726
TI  - Primary care physicians' attitudes to battered women and feelings of self
      competence regarding their care.
AB  - BACKGROUND: Previous descriptive studies have demonstrated the problematic nature
      of physicians' attitudes toward battered women. However, little empirical
      research has been done in the field, especially among the various medical
      specialties. OBJECTIVES: To compare the approach and feelings of competence
      regarding the care of battered women between primary care and non-primary care
      physicians. The non-primary care physicians who are likely to encounter battered
      women in the ambulatory setting are gynecologists and orthopedists. METHODS: A
      self-report questionnaire formulated for this study was mailed to a random sample
      of 400 physicians working in ambulatory clinics of the two main health
      maintenance organizations in Israel (300 primary care physicians, 50
      gynecologists and 50 orthopedists). RESULTS: In both physician groups, treating
      battered women tended to evoke more negative emotional states than treating
      patients with infectious disease. The most prevalent mood state related to the
      management of battered women was anger at her situation. Primary care physicians
      experienced more states of tension and confusion than non-primary care physicians
      and had lower perceived self-efficacy and self-competence in dealing with
      battered women. CONCLUSIONS: Though both physician groups exhibited negative
      feelings when confronting battered women, the stronger emotion of the primary
      care physicians may indicate greater sensitivity and personal awareness. We
      believe that more in-service training should be introduced to help physicians at
      the undergraduate and postgraduate levels to cope both emotionally and
      professionally with these patients.

PMID- 11344727
TI  - A new look at refractive vision.

PMID- 11344728
TI  - The quest for the perfect infant formula.

PMID- 11344729
TI  - The evolving management of penetrating neck injuries.

PMID- 11344730
TI  - Hypercholesterolemia in children.

PMID- 11344731
TI  - Nucleotides in infant nutrition: a must or an option.

PMID- 11344732
TI  - Mucin and colorectal cancer.

PMID- 11344733
TI  - Synovial cyst of the pes anserinus in a patient with rheumatoid arthritis
      presenting as intermittent claudication.

PMID- 11344734
TI  - Unusual presentation of colonic lipomas.

PMID- 11344735
TI  - Glucose-6-phosphate dehydrogenase deficiency: possible determinant for a
      fulminant course of Israeli spotted fever.

PMID- 11344736
TI  - Prostatic tissue in a benign cystic teratoma of the ovary. Report of two cases.

PMID- 11344737
TI  - Tophaceous deposits mimicking osteoarthritic hands.

PMID- 11344738
TI  - Herceptin-taxol related hand and foot syndrome.

PMID- 11344739
TI  - Feeding tolerance of ready-to-use versus powdered formulas in neonates.
AB  - BACKGROUND: Following the introduction of ready-to-use formula in our neonatal
      department, we observed an increase in the number of neonates regurgitating after
      feeding. OBJECTIVE: To compare the feeding tolerance of neonates, in terms of
      regurgitations, to ready-to-use versus powdered formulas. METHODS: We compared
      the number of regurgitations in 727 healthy neonates after feeding ready-to-use
      formulas and powdered formulas of two different manufacturers. Six groups of
      neonates were formed, three for each manufacturer. Each of the two groups was fed
      with either ready-to-use formula or with reconstructed powdered formula (using a
      two-compartment patented feeding bottle called Twist 'N Feed) and one group
      received both preparations during 2 successive days. RESULTS: The groups that
      were fed only with ready-to-use formulas had significantly more regurgitations
      than those fed with powdered formulas. Within the group that received both types
      of formulas there were significantly more regurgitations following the ready-to
      use than the powdered formula. CONCLUSIONS: Feeding tolerance, in terms of
      regurgitations, was significantly better in neonates fed reconstituted powdered
      formula as opposed to ready-to-use formulas. More studies are required to
      determine the exact mechanism for these differences.

PMID- 11344740
TI  - The use of induced sputum in medicine.

PMID- 11344741
TI  - Dexmedetomidine: a promising agent for anesthesia and perioperative care.
AB  - Dexmedetomidine is a relatively new, highly selective, short-acting central alpha
      2 agonist. Although not yet officially introduced for clinical use in Israel, it
      has become increasingly popular among anesthesiologists and intensive care
      physicians abroad when used as an adjuvant to the classical regimen of anesthesia
      techniques. Its administration potentiates the effect of other sedative and
      hypnotic agents while causing minimal respiratory depression. It also blunts the
      sympathetic response--thus minimizing changes in blood pressure and heart rate-
      during critical moments such as laryngoscopy and intubation. However, bradycardia
      and hypotension may ensue. DXM minimizes opioid-induced muscle rigidity and
      attenuates postoperative shivering. These pro-anesthesia effects are attributed
      to the capability of DXM to reduce central adrenergic outflow. Although its
      precise mechanism(s) of action are still debatable, DXM will undoubtedly find an
      increasing role in clinical peri-operative anesthesia.

PMID- 11344742
TI  - The medical school Web site: medical education's newest tool.
AB  - There are few technological advancements that have had as much impact on the
      dissemination of information as the Internet, and especially the worldwide web.
      It is not surprising then that this tool is also changing the way medicine is
      studied, taught and practiced today. This impressive infrastructure enables us to
      teach and study medicine in an entirely different way. The web provides medical
      students and physicians with access to continuing medical education, patient
      education services, telemedicine, and unparalleled communication between
      colleagues via email. The medical school web site may be used as a dynamic
      newspaper or bulletin board to disseminate information internally among the
      faculty as well as to the outside world. It can also be the vehicle for virtual
      learning modules that enhance the medical school core curriculum by including
      lectures, exercises, tests, etc. In addition, the web allows the student access
      to medical literature, medical software applications and medical resource depots.
      To date no work has been published on the medical school web site, its
      construction process, and its advantages, drawbacks and future. The purpose of
      this article is to examine the evolution of the web as a tool for medical
      schools, medical students and associated physicians. We discuss the building of a
      web site for a medical faculty, and look to the future.

PMID- 11344743
TI  - Incidence of phenylketonuria in Israel.

PMID- 11344744
TI  - Empirical treatment of urinary tract infections.

PMID- 11344745
TI  - Empirical treatment of urinary tract infections.

PMID- 11344746
TI  - Pseudohypotension and malignant hypertension.

PMID- 11344747
TI  - Do not disturb!

PMID- 11344748
TI  - Medical research in Israel and the Israel biomedical database.
AB  - The data collected for the second edition of the Directory of Medical Research in
      Israel and the Israel Biomedical Database have yielded very relevant information
      concerning the distribution of investigators, publication activities and funding
      sources. The aggregate data confirm the findings of the first edition published
      in 1996 [2]. Those facts endorse the highly concentrated and extensive nature of
      medical research in the Jerusalem area, which is conducted at the Hebrew
      University and its affiliated hospitals. In contrast, Tel Aviv University, whose
      basic research staff is about two-thirds the size of the Hebrew University staff,
      has a more diffuse relationship with its clinical staff who are located at more
      than half a dozen hospitals. Ben-Gurion University in Beer Sheva and the Technion
      in Haifa are smaller in size, but have closer geographic contact between their
      clinical and basic research staff. Nonetheless, all the medical schools and
      affiliated hospitals have good publication and funding records. It is important
      to note that while some aspects of the performance at basic research institutions
      seem to be somewhat better than at hospitals, the records are actually quite
      similar despite the greater burden of clinical services at the hospitals as
      compared to teaching responsibilities in the basic sciences. The survey also
      indicates the substantial number of young investigators in the latest survey who
      did not appear in the first survey. While this is certainly encouraging, it is
      also disturbing that the funding sources are apparently decreasing at a time when
      young investigators are attempting to become established and the increasing
      burden of health care costs precludes financial assistance from hospital sources.
      The intensity and undoubtedly the quality of medical research in Israel remains
      at a level consistent with many of the more advanced western countries. This
      conclusion is somewhat mitigated by the fact that there is a decrease in
      available funding and a measurable decrease in scholarly activity at a time when
      a new, younger generation of investigators is just beginning to become
      productive. In closing, we wish to stress that the collection of data for the
      Biomedical Database is a continuing project and we encourage all medical
      researches who may not have contributed relevant information to write to the
      Office of the Chief Scientist or contact the office by email.

PMID- 11344749
TI  - Xanthine oxidase and tumor necrosis factor alpha: possible mediators of remote
      tissue injury after viper envenomation.
AB  - BACKGROUND: Tumor necrosis factor is associated with various local and systemic
      inflammatory sequelae following snakebite. Xanthine oxidase is a principal
      mediator of remote tissue injury (e.g., lungs, heart, liver). OBJECTIVE: To
      investigate in a snakebite-like animal model the as yet unexplored role of TNF
      and XO in mediating organ damage following snakebite. METHODS: Sprague-Dawley
      rats were injected intramuscularly with a non-lethal 500 micrograms/kg dose of
      Vipera aspis venom (n = 10) or saline (n = 10). Blood pressure and heart rate
      were continuously monitored, TNF-alpha was measured in the blood, and total XO +
      xanthine dehydrogenase activity was assessed in various tissues. Lung histology
      and permeability indices were analyzed. RESULTS: Venom injection caused a
      significant (P < 0.05) reduction in both heart rate and invasive arterial
      pressure. The blood circulating TNF levels were significantly higher in the
      intoxicated group (P < 0.05 vs. saline group), with changes seen at 30 minutes
      from intoxication in both groups. Total XO + XDH activity in the kidney, lung and
      liver of the venom-injected group was significantly (P < 0.05) higher than in the
      saline group, while the activity in the heart was similar. CONCLUSIONS: The
      mediation of remote organ and hemodynamic changes following intramuscular
      injection of a non-lethal dose of Vipera aspis venom can be attributed partly to
      TNF and partly to XO. More research is needed to better understand the role of
      either compound and the time frame of their activity before specific antagonists
      can be introduced for snakebite management.

PMID- 11344750
TI  - Immunodetection of living trophoblast.
AB  - BACKGROUND: Human chorionic gonadotropin, the pregnancy hormone, is synthesized
      by trophoblast cells which make up the placenta. OBJECTIVE: To determine whether
      antibody to hCG can be used to specifically detect living trophoblast in vitro by
      binding to the external membrane. METHODS: Trophoblast was isolated from fresh
      placentas of women undergoing termination of pregnancy in the first trimester and
      incubated with monoclonal antibody to hCG. Anti-mouse immunoglobulin G with a
      fluorescent marker was then added. RESULTS: Syncytiotrophoblast stained positive
      on the external surface of the cell, while controls of leukocytes, endometrial
      cells and hepatocytes were negative. CONCLUSION: The hCG monoclonal antibody may
      be used to specifically detect hCG on the surface of living trophoblast in vitro.

PMID- 11344751
TI  - Job satisfaction among certified and non-certified general practitioners.
AB  - BACKGROUND: The aim of family medicine is to provide patients with comprehensive
      care within the biopsychosocial model. High job satisfaction is necessary to
      attract physicians to this specialty. OBJECTIVE: To compare job satisfaction
      levels between primary physicians with training in family medicine and physicians
      without specialty training. METHODS: A self-report questionnaire, the "Task
      Profiles of General Practitioners in Europe," was mailed to a stratified random
      sample of 664 primary care physicians in Israel. The response rate was 77.6%.
      Bivariate and logistic regression procedures were used to analyze the data.
      RESULTS: Physicians with training in family medicine were less satisfied with the
      rewards for their work than general practitioners with no formal specialization
      in family medicine. Satisfaction with the intrinsic aspects of the work was found
      to be equal. Women and rural physicians were more satisfied than men and urban
      physicians. CONCLUSION: Measures should be taken by health maintenance
      organizations to increase the level of job satisfaction of specialist-certified
      family physicians to avoid a crisis in the profession.

PMID- 11344752
TI  - A worrying increase in the incidence of mesothelioma in Israel.
AB  - BACKGROUND: Exposure to asbestos is the main established cause of mesothelioma;
      the incidence of this tumor is thus often interpreted as an index of past
      exposure. Asbestos has been widely used in Israel in industry and building,
      exposing certain population groups to the risk of developing mesothelioma.
      OBJECTIVES: To analyze the incidence of mesothelioma in Israel during the years
      1960-96, and to project its trend for the following years. METHODS: We conducted
      a population-based study of the incidence of mesothelioma reported to the Israel
      Cancer Registry during 1960-96. Time trends were analyzed from data on the annual
      import of asbestos to Israel, which may indicate the magnitude of past exposure.
      Based on these findings, trends in the incidence of mesothelioma in Israel were
      projected for the subsequent years. RESULTS: A total of 327 cases of mesothelioma
      were reported to the Israel Cancer Registry during the study period. The
      incidence in Jews was higher than in Arabs (age-standardized incidence rate 2.64
      vs. 1.35 per million/year, respectively). Among the Jewish population, Israeli
      born males and males born in Europe and America showed the highest incidence (ASR
      4.23 and 4.15 per million/year, respectively). Israeli-born males were 20 years
      younger than Jewish males born elsewhere. The incidence was twice as high among
      males than females and increased sevenfold from its nadir (1.17 per million/year)
      in 1978-80 to its peak (8.5 per million/year) in 1993-96. During a similar period
      the incidence among females increased from 0.33 to 2.56 per million/year. The
      incidence in both sexes does not appear to level off. The large wave of
      immigration from the former Soviet Union that began in 1989 only partly accounts
      for the increased incidence in 1993-96. The time trend in the incidence of
      mesothelioma in both sexes parallels the use of asbestos in Israel, which peaked
      in the years 1976-78. CONCLUSIONS: The incidence of mesothelioma in Israel has
      increased sharply in recent years, unrelated to a wave of immigration from East
      Europe, and is predicted to continue to rise for another 10-15 years.

PMID- 11344753
TI  - Determinants of hospital utilization: the situation in Israel and selected
      countries.
AB  - BACKGROUND: In 1995 hospital costs constituted about 42% of the health
      expenditures in Israel. Although this proportion remained stable over the last
      decade, hospital discharge rates per 1,000 population increased, while
      hospitalization days per 1,000 population and average length of stay declined.
      OBJECTIVE: To gain an insight into the forces behind these changes, we compared
      the trends in hospital utilization in Israel with those in 21 developed countries
      with available data. MATERIALS AND METHODS: Our data were derived from The
      "Hospitals and Day Care Units, 1995" report by the Health Information and
      Computer Services of the Israel Ministry of Health, and the Organization for
      Economic Cooperation and Development Health Data, 98. We examined the numbers of
      acute care hospital beds, of patients on dialysis and of doctors' consultations,
      health expenditures and age structure of the population in 1995 or closest year
      with available data, as well as changes in DRs, HDs and ALOS between 1976 and
      1995. RESULTS: In Israel the DRs increased from 130 in 1976 to 177 in 1995 (36%),
      HDs declined from 992 to 818 (18%), and ALOS declined from 7.60 to 4.51 days
      (41%). Relative to other countries, in 1995 Israel had the lowest ALOS; low HDs
      similar to those in the UK, Portugal, Spain, the USA and Sweden; and intermediate
      DRs similar to those in Belgium, Germany, Sweden and Australia. The number of
      acute care beds per 1,000 population was directly related to HDs (r = 0.954, P =
      0.000) and to DRs (r = 0.419, P = 0.052). Health expenditures (% of the gross
      national product) correlated with the number of patients on dialysis per
      1,000,000 population (r = 0.743, P = 0.000). Between 1976 and 1995, HDs and ALOS
      declined in most countries, however the trends in DRs varied from an increase by
      119% in the UK to a decline by 29% in Canada. CONCLUSIONS AND HYPOTHESES: The
      increase in DRs in Israel from 1976 to 1995 was shared by many but not all
      countries. This variability may be related to differences in trends in local
      practice norms and in available hospital beds. If the number of patients on
      dialysis is a valid index for use of expensive treatment modalities, the
      correlation of health expenditures with the number of patients on dialysis
      suggests that the use of expensive technology is a more important determinant of
      health care costs than the age of the population or hospital utilization. Since
      the use of expensive technology is highest during the first few days in hospital,
      decisions about health care policy should consider the possibility that the
      savings incurred by a further decline in HDs and ALOS may be offset by a possible
      increase in per diem hospital costs and in health care expenditures after
      discharge from hospital.

PMID- 11344754
TI  - The role of the placenta in the maintenance of normal pregnancy.

PMID- 11344755
TI  - Selective cyclooxygenase-2 inhibition: biological and clinical effects.

PMID- 11344756
TI  - Silent myocardial ischemia: an update.

PMID- 11344757
TI  - The detection of micrometastases: is it a relevant clinical parameter?

PMID- 11344758
TI  - Genetic factors in clozapine-induced agranulocytosis.

PMID- 11344759
TI  - Inferior vena cava (pseudo)thrombus: computed tomographic artifact occurring with
      right heart failure and tricuspid incompetence.

PMID- 11344760
TI  - Computed tomography diagnosis of a perforating malpositioned central venous
      catheter.

PMID- 11344761
TI  - Metastatic breast tumors imitating primary colonic malignancies.

PMID- 11344762
TI  - The spectrum of "cerebral hyponatremia"--cerebral salt wasting syndrome in a
      patient with pituitary adenoma.

PMID- 11344763
TI  - Pulmonary function during the perioperative period.

PMID- 11344764
TI  - Before-use admixture of components stored in a two-chamber container: possible
      medical and nutritional applications of the recotec technology.

PMID- 11344765
TI  - Spontaneous intramural esophageal hemorrhage.

PMID- 11344766
TI  - Omphalocele with extra-corporeal liver.

PMID- 11344767
TI  - Relationship between prostate size and percent free prostate-specific antigen in
      patients with operable prostate cancer.
AB  - BACKGROUND: The free-to-total prostate-specific antigen ratio is the best marker
      for optimizing prostate cancer detection. The main problem with studies of
      percent free PSA is the variability of reported cutoff values. OBJECTIVES: To
      evaluate the influence of prostate size on the ratio of free to total PSA.
      METHODS: The study group included 58 patients (mean age 66.4 years) with
      clinically localized prostate cancer treated surgically at our institution. Total
      PSA and free PSA levels were measured by a solid phase enzyme immunoassay test
      (Hoffman-La Roche, Basel, Switzerland). The percent free PSA was compared with
      prostate size as determined from the surgical specimen. RESULTS: A direct
      relation was noted between prostate size and the percent free PSA value (r =
      0.49, P = 0.0001). Mean percentage free PSA was 9% +/- 0.004 in men with normal
      sized gland while in men with large prostate (> 60 g) the average percent free
      PSA was 15.9 +/- 0.09 (P = 0.001). CONCLUSIONS: In patients with prostate cancer
      the percent free PSA level is influenced by the gland size. The larger the
      prostate the higher the proportion of the free PSA. Such information may have
      influence on the recommendation for prostate biopsy in screening programs for
      early detection of prostate cancer.

PMID- 11344768
TI  - Additive deleterious effect of smoking on gastroduodenal pathology and clinical
      course in Helicobacter pylori-positive dyspeptic patients.
AB  - BACKGROUND: Cigarette smoking has long been regarded as an important factor in
      the pathogenesis of peptic ulcer disease. OBJECTIVE: To investigate whether
      cigarette smoking has an additive effect on the clinical presentation and course
      of disease in Helicobacter pylori-positive dyspeptic patients. PATIENTS AND
      METHODS: The study group comprised 596 consecutive H. pylori-positive dyspeptic
      patients (334 males and 262 females, mean age 50.6, range 12-81 years). Following
      upper gastrointestinal endoscopy, patients were subdivided by diagnosis as
      follows: Non-ulcer patient group (n = 312: gastritis 193, duodenitis 119),
      gastric ulcer (n = 19), and duodenal ulcer (n = 265). H. pylori infection was
      confirmed by histology and/or rapid urease test. In addition, 244 patients had a
      positive 14C-urea breath test prior to antimicrobial treatment. The patients'
      medical history and smoking habits were obtained using a detailed questionnaire
      completed by the patients and their referring physicians. RESULTS: There were 337
      non-smoking patients, 148 current smokers and 111 past smokers. Gastric and
      duodenal ulcers were significantly less prevalent in non-smokers than in current
      or past smokers (gastric 1.8%, 4.1%, 6.3%; duodenal 39.8%, 50%, 51.4%,
      respectively) (P < 0.05). The incidence of gastrointestinal bleeding was
      significantly lower in non-smokers than in current or past smokers (7.1%, 8.1%
      and 20.7%, respectively) (P < 0.05). Bacterial density, as assessed by the UBT
      value in 244 patients, was higher in non-smokers (mean 352.3 +/- 273 units) than
      in past smokers (mean 320.8 +/- 199) or current-smokers (mean 229.9 +/- 162) (P <
      0.05). Logistic regression analysis revealed that male gender, current smoking,
      and immigration from developing countries were all significant independent risks
      for developing duodenal ulcer, while only past smoking was associated with a
      higher rate of upper gastrointestinal bleeding in the past. CONCLUSIONS: In H.
      pylori-positive dyspeptic patients, current smoking as well as male gender and
      immigration from developing countries are associated with an increased risk for
      duodenal ulcer. This effect does not seem to be related to the bacterial density
      or increased urease activity of H. pylori organisms.

PMID- 11344769
TI  - Primary epiploic appendagitis: clinical and radiological manifestations.
AB  - BACKGROUND: Primary epiploic appendagitis is a relatively rare condition in which
      torsion and inflammation of an epiploic appendix result in localized abdominal
      pain. This is a non-surgical situation that clinically mimics other conditions
      requiring surgery such as acute diverticulitis or appendicitis. OBJECTIVE: To
      investigate the clinical, laboratory and radiological findings of the disease.
      METHODS: During the years 1995-88 five patients with primary epiploic
      appendigitis were diagnosed at our institution. The clinical, laboratory and
      imaging results were summarized and compared to previously reported series.
      Emphasis was placed on the computed tomography findings, which are the gold
      standard for diagnosis. RESULTS: All our patients (two males and three females,
      mean age 47 years) presented with left lower quadrant abdominal pain. CT proved
      to be the imaging modality of choice in all patients by showing a pericolic fatty
      mass with an increased attenuation as compared to normal abdominal fat. In all
      cases the mass was surrounded by a high attenuation rim, and focal stranding of
      the fat was observed. In no case was there thickening of the adjacent bowel wall.
      This serves as an important, and previously unreported, clue for diagnosis.
      CONCLUSION: Primary epiploic appendagitis is a relatively rare condition that may
      be clinically misdiagnosed, resulting in unnecessary surgical intervention.
      Judicious interpretation of CT may lead to early diagnosis and ensure proper
      conservative treatment.

PMID- 11344770
TI  - Influenza vaccination among healthcare workers.
AB  - OBJECTIVE: To determine the vaccination rates among healthcare workers in the
      Haifa subdistrict and to assess factors associated with vaccination uptake among
      them. METHODS: The study was conducted in the three general hospitals in Haifa
      City, and in five nursing homes in the Haifa subdistrict. Self-administered
      questionnaires were distributed to 1,014 employees of whom 71% were females, 34%
      were nurses, 27% were physicians and 28% were non-professional workers. RESULTS:
      The crude response rate was 66%. Response rates were higher in females (71%) than
      in males (49%), in nurses (70%) than in physicians (43%), and in staff of
      internal and pediatric departments than in workers of surgery departments and
      emergency rooms. The overall vaccination rate among the respondents was 11%,
      which was higher among males (15%) than among females (10%). No significant
      relationship between vaccination rate and age, occupation and department was
      found. The vaccination rate among employees with chronic illness was very low
      (7%). Influenza vaccine was actively recommended to 29% of the employees. The
      main reasons for non-compliance were low awareness of the severity of the disease
      and of the vaccine's efficacy and safety, and unavailability of the vaccine
      within the workplace. CONCLUSIONS: Educational efforts and offering the vaccine
      at the workplace at no cost are the most important measures for raising influenza
      vaccination rates.

PMID- 11344771
TI  - Factors associated with performance of influenza immunization among the elderly.
AB  - BACKGROUND: Influenza is a major cause of morbidity and mortality in the elderly.
      While immunization has been shown to reduce these complications, many of the
      elderly are not immunized. OBJECTIVE: To identify correlates for under
      utilization of influenza immunization among the elderly. METHODS: A telephone
      survey was conducted among a random sample of patients aged 65 and over
      registered at a Jerusalem primary care community clinic. The 626 questionnaires
      were analyzed for associations of immunization receipt for the latest influenza
      season. Multivariate logistic regression was performed to identify independent
      correlates. Respondents were also asked what factors had influenced their
      decision about immunization. RESULTS: The most frequently reported influence on
      getting immunized was a physician's recommendation. Immunization was
      independently associated with the identity of the primary care physician (P <
      0.0001) and with having visited the physician during the previous 3 months (P =
      0.0006). Immunization was more likely among persons who believed that it provides
      complete protection from influenza (P < 0.0001) and less likely among those who
      believed immunization can cause influenza (P < 0.0001). Higher immunization rates
      were also associated with being married (P = 0.0031). CONCLUSION: Through their
      influence on patient knowledge and the effect of their recommendation, primary
      care physicians play a pivotal role in determining immunization rates. Physicians
      should routinely discuss the effects of immunization and recommend it to the
      elderly.

PMID- 11344772
TI  - Epidemiology of ceftazidime-resistant Klebsiella pneumoniae in a large university
      hospital in Tel Aviv.
AB  - BACKGROUND: An increase in multiple drug-resistant Klebsiella pneumoniae due to
      extended spectrum beta-lactamase production has recently been reported from many
      centers around the world. There is no information in the literature regarding
      this problem in Israel. A high prevalence of ceftazidime-resistant K. pneumoniae
      was noted in our Intensive Care Unit in the first few months of 1995. OBJECTIVE:
      To describe the epidemiology of ceftazidime-resistant K. pneumoniae in our
      medical center, as representing the situation in tertiary care hospitals in
      Israel. METHODS: We vigorously restricted the use of ceftazidime in the ICU and
      enforced barrier precautions. The susceptibility rate of K. pneumoniae was
      surveyed in the ICU and throughout the hospital before and after the intervention
      in the ICU. RESULTS: Following the intervention, the susceptibility rate of K.
      pneumoniae increased from 11% (3/28) to 47% (14/30) (P < 0.01) among ICU
      isolates, from 55% (154/280) to 62% (175/281) (P = 0.08) among total hospital
      isolates, and from 61% (50/82) to 74% (84/113) (P < 0.05) among total hospital
      blood isolates, although no additional control measures were employed outside the
      ICU. CONCLUSIONS: The epidemiology of ceftazidime-resistant K. pneumoniae in our
      medical center is similar to that reported from other centers around the world.
      Early awareness to the emergence of this resistance, identification of the source
      of the epidemic, and prompt action at the putative source site may reduce the
      rate of acquisition and spread of such resistance inside and outside of the
      source unit.

PMID- 11344773
TI  - Compliance with influenza vaccination and the health belief model.

PMID- 11344774
TI  - Influenza vaccination.

PMID- 11344775
TI  - Multifactorial changes in human behavior, environment, climate vectors and
      zoonoses enhance the emergence and reemergence of human microbial diseases.

PMID- 11344776
TI  - Emerging infectious diseases: a cause for concern.
AB  - As the twenty-first century begins it becomes increasingly apparent that the
      twentieth century, which opened with the promise of the eradication of most
      infectious diseases, closed with the specter of the reemergence of many deadly
      infectious diseases that have a rapidly increasing incidence and geographic
      range. Equally if not more alarming is the appearance of new infectious diseases
      that have become major sources of morbidity and mortality. Among recent examples
      are HIV/AIDS, hantavirus pulmonary syndrome, Lyme disease, hemolytic uremic
      syndrome (caused by a strain of Escherichia coli), Rift Valley fever, Dengue
      hemorrhagic fever, malaria, cryptosporidiosis, and schistosomiasis. The reasons
      for this situation are easily identified in some cases as associated with
      treatment modalities (permissive use of antibiotics), the industrial use of
      antibiotics, demographic changes, societal behavior patterns, changes in ecology,
      global warming, the inability to deliver minimal health care and the neglect of
      well-established public health priorities. In addition is the emergence of
      diseases of another type. We have begun to characterize the potential microbial
      etiology of what has historically been referred to as chronic diseases.

PMID- 11344777
TI  - Drug-induced QT prolongation.

PMID- 11344778
TI  - Interactions of angiotensin-converting enzyme, kinins and nitric oxide in
      circulation and the beneficial effects of ACE inhibitors in cardiovascular
      diseases.
AB  - Renin-angiotensin-aldosterone systems play a critical role in the development and
      progression of cardiovascular diseases, and inhibitors of angiotensin-converting
      enzyme have proven effective for the treatment of these diseases. Since
      angiotensin II receptor antagonists can inhibit the effects of angiotensin II via
      ACE-independent pathways, e.g., chymase, they were considered to be more
      effective than ACEIs. On the other hand, ACE inhibitors can increase bradykinin,
      and thus, nitric oxide, which may cause potent cardioprotection, inhibition of
      smooth muscle proliferation and attenuation of inflammation mechanisms. It
      appears that angiotensin II receptor antagonists and ACEIs may mediate
      cardioprotection in different ways. This is the rationale to explore the
      possibility of a combined administration of both drugs for the treatment of
      chronic heart failure and other cardiovascular pathology. In this review we try
      to analyze the role of ACE, kinins and chymase inhibition in the pathophysiology
      and treatment of cardiovascular diseases.

PMID- 11344779
TI  - Stem cell transplantation in systemic sclerosis: rationale and status report.
AB  - The rationale for stem cell transplantation is feasible and tests the hypothesis
      that the immune system is important in the pathogenesis of SSc in carefully
      selected patients. At the present time, results from pilot studies of SCT in
      systemic sclerosis are moderately encouraging, although further refinements in
      SCT treatment protocols are probably necessary. Finally, the time for a
      controlled study of SCT is rapidly approaching.

PMID- 11344780
TI  - Physiologic assessment of magnesium status in humans: a combination of load
      retention and renal excretion.

PMID- 11344781
TI  - Acute bleomcyin-induced pneumonitis mimicking lobar pneumonia: reversal with high
      dose corticosteroids.

PMID- 11344783
TI  - Late paraplegia in diastematomyelia.

PMID- 11344782
TI  - Oncogenic osteomalacia.

PMID- 11344784
TI  - Human bite on penile shaft from oral sex as a portal of entry for streptococcal
      toxic shock syndrome.

PMID- 11344785
TI  - Neoadjuvant chemoradiation treatment of locally advanced adenocarcinoma of the
      duodenum.

PMID- 11344786
TI  - Anesthesia simulators--technology and applications.
AB  - Anesthesia simulators are rapidly becoming more prevalent worldwide. Several
      types of anesthesia simulators utilizing a variety of technologies are available.
      High fidelity mannequin-based simulators, low fidelity screen-based simulators,
      and relatively inexpensive intermediate fidelity simulators have found
      applications in training, assessment of clinical competence, and research. A
      number of recent studies support the use of anesthesia simulators and may lead to
      widespread adoption of simulation in other fields of medicine.

PMID- 11344787
TI  - A multidisciplinary forum for ethics in medicine: our seven years experience.
AB  - The Rappaport Faculty of Medicine of the Technion established an Ethics in
      Medicine Forum in March 1993. The main objective of the forum was to increase
      awareness of the philosophical principles of ethics in medicine, as defined and
      developed in the western world during the last three decades. The
      multidisciplinary forum meets once a month during the academic year. Our 7 years
      experience is documented. Of the 45 meetings, 30 were clinically oriented and of
      these more than half were based on cases. Only 15 meetings were purely
      theoretical. Our principal assumption was that any and every topic could be
      discussed, including those covered by the law. We explored how well western
      philosophical principles and rules fit the Israeli picture. Many of the forum
      discussions related to the draft of the Patient's Bill of Rights, which came into
      effect on 12 May 1996. The role of the "legal" hospital ethics committees was
      compared to that of the "advisory" ethics committees whose members constituted a
      large share of our forum. The multicultural Israeli population and the practice
      of medicine therein raised many lively discussions. The principle of autonomy in
      the ultraorthodox and in the family setting was a highly controversial issue. The
      forum served as a workshop for examining traditional medical ethical principles,
      which we strongly feel needs to be amended in light of the 1996 Patient's Bill of
      Rights. From our 7 years experience with an Ethics in Medicine Forum we recommend
      that medical ethical deliberations focus on genuine medical cases.

PMID- 11344788
TI  - Save the fledgling research in Israel's Hospital.

PMID- 11344789
TI  - Magnetic nose-rings: a plea for caution.

PMID- 11344790
TI  - Non-rheumatic myopericarditis and GABHS--an unusual twist.

PMID- 11344791
TI  - Inhibition of the malaria parasite by experimental co-infection of mice by West
      Nile virus and Plasmodium berghei.

PMID- 11344792
TI  - Iloprost treatment of finger gangrene in a patient with Raynaud's syndrome.

PMID- 11344793
TI  - Evaluation of C-reactive protein, fibrinogen and antithrombin-III as risk factors
      for coronary artery disease.
AB  - BACKGROUND: Inflammation is an important feature of atherosclerotic lesions and
      increased production of the acute-phase reactant. The contribution of coagulation
      factor to the development of coronary artery disease has not yet been clearly
      established. OBJECTIVES: To test whether C-reactive protein, fibrinogen and
      antithrombin-III are associated with angiographic CAD, history of myocardial
      infarction and extensive atherosclerotic involvement. METHODS: Blood samples were
      tested for CRP, fibrinogen and AT-III levels from 219 individuals undergoing
      coronary angiography. RESULTS: CRP was higher in patients with CAD (0.95 +/-
      1.31, n = 180, vs. 0.39 +/- 0.61 mg/dl, n = 39, P < 0.0001) and in those with a
      history of MI (1.07 +/- 1.64, n = 96, vs. 0.65 +/- 0.72 mg/dl, n = 84, P < 0.05)
      than in control subjects. The patients who developed unstable angina had higher
      CRP levels than the patients with stable CAD (2.07 +/- 2.38, n = 7, vs. 0.80 +/-
      1.13 mg/dl, n = 173, P < 0.001). Fibrinogen was significantly higher in patients
      with CAD than in those without CAD (298 +/- 108 vs. 258 +/- 63 mg/dl, P < 0.01).
      In patients with CAD, mean AT-III value was less than in patients without CAD,
      but this difference was not statistically significant (P = 0.08). No difference
      was found in CRP, fibrinogen and AT-III values among the patients with single,
      double or triple vessel disease. CONCLUSIONS: CRP is elevated in patients with
      CAD and a history of MI. Elevated levels of CRP at the time of hospital admission
      is a predictive value for future ischemic events. There is an association between
      higher levels of fibrinogen and CAD. The association of AT-III levels with CAD
      needs testing in further studies.

PMID- 11344794
TI  - A four year survey of neonatal narcotic withdrawal: evaluation and treatment.
AB  - BACKGROUND: Narcotic abuse has steadily become more prevalent in Israel and may
      result in an increasing number of children exposed prenatally to narcotics, with
      a consequent increase in the number of infants born with neonatal abstinence
      syndrome. OBJECTIVE: To report our experience with infants born to narcotic
      addicted women between the years 1995 and 1998 at the Soroka University Medical
      Center. METHODS: The medical records of 24 newborns and their drug-addicted
      mothers admitted to our Medical Center for parturition were analyzed
      retrospectively. A diagnosis of NAS was established on the basis of the clinical
      presentation and anamnesis. The Finnegan Neonatal Abstinence Scoring System was
      used to assess drug withdrawal. Urine toxicological analysis for narcotics was
      done only for the year 1998. RESULTS: Of the 24 newborn infants exposed
      prenatally to narcotics 23 (96%) developed NAS, and 78% (18 of the 23) had a
      Finnegan score of 8 or more. These 18 infants were treated pharmacologically
      (tincture of opium and/or phenobarbital) until the score was reduced to less than
      8, after which they received supportive treatment. In one child who became
      lethargic after the first dose of tincture of opium, the medication was stopped
      and supportive treatment alone was given. Four of the five neonates with scores
      of 7 and less were given supportive treatment. One of five infants who had a low
      Finnegan score at birth nevertheless received pharmacological therapy to prevent
      further deterioration of his physical state since he was born with severe
      dyspnea. Ten of the 24 children (42%) were followed for lengths of time ranging
      from 6 to 22 months after discharge, all of whom showed normal development.
      CONCLUSIONS: About three-quarters of newborns exhibiting withdrawal syndrome
      required pharmacological therapy. Previous information on maternal drug abuse is
      a crucial criterion for early detection and treatment.

PMID- 11344795
TI  - Hospitalization for general medical conditions among diabetic patients in Israel.
AB  - BACKGROUND: Diabetes mellitus is a serious, costly and growing public health
      problem. Very few studies have been published on the economic impact of diabetes
      in Israel. OBJECTIVE: To estimate health fund expenditures and rates of
      hospitalization for general conditions among the diabetic population in Israel.
      METHODS: The total number of hospitalizations in Israel in 1998 of beneficiaries
      of the General Sick Fund (Kupat Holim Clalit) was obtained from its bureau of
      statistics. The diabetic and general populations were compared for age and gender
      distribution, days of hospitalization and cost of hospitalization. All hospitals
      in Israel were included. RESULTS: There were 618,317 general admissions for a
      total of 3,005,288 hospitalization days. The diabetic population accounted for
      11.5% of all admissions and 13.7% of all hospitalization days. Analysis by age
      revealed that diabetic patients over age 45 represented 18.3% of all admissions
      and 17.5% of all hospitalization days. The average stay in hospital was 4.8 days
      per patient for the general population and 5.3 days for diabetic patients. The
      overall hospital expenditure of the GSF for general medical conditions among
      diabetic patients in 1998 was estimated at US $173,455,790, of which 57%
      accounted for the daily hospitalization cost. Of the total hospital expenditures
      for that year, 13.3% was allocated to patients with diabetes of whom 96.4% were
      over 45 years old. No significant difference was found between males and females.
      CONCLUSION: Hospital expenditures for diabetic people increase with patient age
      and represent one-fifth of the total health insurance expenditure for the middle
      aged and elderly population.

PMID- 11344796
TI  - Prognostic score for patients with localized renal cell carcinoma treated by
      nephrectomy.
AB  - OBJECTIVE: To evaluate the feasibility of using combined clinical and
      histomorphometric features to construct a prognostic score for the individual
      patient with localized renal cell carcinoma. PATIENTS AND METHODS: We studied 39
      patients with pT1 and pT2 RCC who underwent radical nephrectomy between 1974 and
      1983. Univariate and multivariate analyses were used to determine the association
      between various prognostic features and patient survival. RESULTS: The most
      important and independent predictors of survival were tumor angiogenesis (P =
      0.009), nuclear DNA ploidy (P = 0.0071), mean nuclear area (P = 0.013), and mean
      elongation factor (P = 0.0346). Combination of these variables enabled prediction
      of outcome for the individual patient at a sensitivity and specificity of 78% and
      89%, respectively. CONCLUSION: Our results indicate that no single parameter can
      accurately predict the outcome for patients with localized RCC. Combination of
      neovascularity, DNA content and morphometric shape descriptors enabled a more
      precise stratification of the patients into different risk categories.

PMID- 11344798
TI  - Hospital campaign anti-bug 2000 as leverage for promoting continuous quality
      improvement.
AB  - The management of a 750-bed tertiary care university hospital that serves the
      Jerusalem area and nationwide referrals initiated a total overhaul of all its
      supporting systems. This program, with parallel contingency plans, ensured a
      smooth transition of all computer-dependent and other services into the year
      2000. Because this extraordinary project proved successful, its outcomes are now
      being utilized as a unique impetus for implementation of hospital-wide continuous
      quality improvement programs. This paper reports how the established QI
      procedures, which were introduced also during the campaign, are now being
      activated from the baseline of those outcomes that have provided absolute
      efficacy in all hospital activities. The success of the campaign was achieved
      through the total involvement of all staff. This involvement was enhanced by the
      popular appeal of the dramatic deadline of the date 2000, as well as by focusing
      attention on personnel dynamics. Strategies for sustaining the momentum must be
      considered.

PMID- 11344797
TI  - Analysis of fractures of the proximal femur in the Jordanian population.
AB  - BACKGROUND: Proximal femur fractures represent a challenging medical problem
      worldwide. In recent years numerous reports have documented a progressive
      increase in the incidence of hip fractures. In Jordan, this problem has not
      received sufficient attention, and to my knowledge, this is the first study to
      address the problem. OBJECTIVE: To analyze the predisposing factors involved in
      the occurrence of proximal femur fractures seen at a major medical center in
      Jordan. METHODS: A retrospective analysis was conducted of all patients admitted
      with hip fractures to King Hussein Hospital and the Royal Jordanian
      Rehabilitation Center at the King Hussein Medical Center over a 2 year period (1
      January 1995 to 31 December 1996). We determined the associated chronic diseases
      and medications, mechanisms of injury, types of fractures and other circumstances
      in order to suggest preventive measures to decrease the incidence of this
      clinical problem. RESULTS: We identified 216 cases of fracture: 43% occurred in
      people over the age of 80 years, 95% were due to low energy injuries (falls), and
      69.5% occurred in females. Two or more co-morbid medical conditions were present
      in 70% of the cases. CONCLUSIONS: Since fractures of the hip in the study
      population in Jordan occurred predominantly as low energy injuries in the
      elderly, preventive measures should focus on fall avoidance.

PMID- 11344799
TI  - Transcatheter closure of secundum atrial septal defects with the amplatzer septal
      occluder: early experience.
AB  - BACKGROUND: Secundum atrial septal defect is a common congenital heart defect
      that causes right heart volume overload and produces symptoms usually after the
      third decade of life. Treatment until the last few years has been open heart
      surgery. OBJECTIVES: To review our early experience with transcatheter closure of
      ASD2 using the Amplatzer septal occluder. METHODS: Between November 1999 and
      February 2000, 20 children and young adults with a median age of 9.1 years (4.2
      35.1 years) were referred for transcatheter closure of ASD2. Diagnosis was
      established by transthoracic echocardiography. Implantation was performed under
      general anesthesia through the femoral vein with the guidance of transesophageal
      echocardiography and fluoroscopy. Femoral arterial puncture was performed for
      blood pressure monitoring during the procedure. The device size chosen was
      similar to the balloon-stretched diameter of the ASD2. RESULTS: Implantation was
      completed successfully in 18 patients. Two patients were referred for elective
      surgery: one had an unsuitable anatomy for transcatheter closure by TEE in the
      catheterization laboratory and the device could not be implanted properly, the
      other patient had a large multiperforated septal aneurysm that was retrieved.
      Mean ASD2 diameter by TTE and TEE was similar (13.9 +/- 3 mm, 13.4 +/- 3.5 mm)
      and mean stretched diameter was 18.3 +/- 4.3 mm. Mean Qp:Qs (pulmonary
      flow:systemic flow) was 2.2 +/- 0.6. Mean fluoroscopy time for the procedure was
      14.8 +/- 4.8 minutes. The patients were discharged the day after the procedure.
      Four patients had a tiny leak immediately post-procedure, and none had a leak at
      one month follow-up. The only complication was a small pseudoaneurysm of the
      femoral artery in one patient, that resolved spontaneously. CONCLUSIONS:
      Transcatheter closure of ASD2 with the Amplatzer septal occluder is a safe and
      effective alternative to surgical closure. Long-term outcome has to be evaluated.

PMID- 11344800
TI  - Acute-phase response and thrombin generation in predicting coronary risk.

PMID- 11344801
TI  - Post-catheterization false aneurysms.

PMID- 11344802
TI  - Current advances in liver support systems.

PMID- 11344803
TI  - Liver support systems.
AB  - In recent years liver transplantation was shown to be the only clinically
      effective method of treating acute or chronic hepatic failure due to various
      causes. However, this ultimate therapeutic approach is limited by the growing
      disparity between organ donation and the number of patients on the waiting list.
      Factors such as high cost, morbidity, and the need for lifelong immunosuppression
      accelerated the research on alternative methods to support the failing liver.
      Recently, new technologies incorporating hepatocytes and extracorporeal
      circulation devices were introduced for liver support. This review presents
      current knowledge on liver support systems and their role in the treatment of
      acute liver failure.

PMID- 11344804
TI  - Arterial false aneurysms and their modern management.
AB  - BACKGROUND: Both diagnostic and therapeutic options in the management of
      iatrogenic false aneurysms have changed dramatically in the last decade, with
      surgery being required only rarely. OBJECTIVE: To describe our experience,
      techniques and results in treating pseudoaneurysms at a large medical center with
      frequent arterial interventions. We emphasize upper limb lesions. MATERIALS AND
      METHODS: We reviewed the data of all consecutive patients diagnosed by color
      coded duplex Doppler between August 1992 and July 1998 as having upper limb and
      lower limb pseudoaneurysms (mainly post-catheterization). We accumulated 107
      false aneurysms (mainly post-catheterization lesions): 5 were upper limb lesions
      and 102 were groin aneurysms. RESULTS: In the lower limb cases 94 of the 102
      lesions were not operated upon (92.1%). Seventy lower limb cases were treated non
      operatively by ultrasound-guided compression obliteration with a 95.7% success
      rate (67 cases). Two cases were treated by percutaneous thrombin injection (2%)
      and 23 by observation only (22.5%). Altogether 12 patients underwent surgery
      (11.2%): 4 upper extremity and 8 lower extremity cases. None of the lower limb
      group suffered serious complications regardless of treatment, but all five upper
      limb cases did, four of them necessitating surgical intervention. Three of the
      five upper limb cases had a grave outcome with severe or permanent functional or
      neurological damage. CONCLUSION: Most post-catheterization pseudoaneurysms can be
      managed non-surgically. False aneurysms in the upper extremity are rare,
      comprising less than 2% of all lesions. However, upper extremity pseudoaneurysms
      present a potentially more serious complication and require early diagnosis and
      prompt intervention to minimize the high complication rate and serious long-term
      sequelae. Prevention can be achieved by proper puncture technique and site
      selection, and correct post-procedure hemostatic compression with or without an
      external device. Some upper limb lesions are avoidable if the axillary artery is
      not punctured.

PMID- 11344805
TI  - C-reactive protein and vascular disease.

PMID- 11344806
TI  - Visits to physicians: a critical review of the literature on ambulatory
      utilization in Israel.

PMID- 11344807
TI  - Diabetic foot ulcers: principles of assessment and treatment.

PMID- 11344808
TI  - Sarcoidosis presenting as primary Sjogren's syndrome.

PMID- 11344809
TI  - Isolated epididymal vasculitis.

PMID- 11344810
TI  - Acute respiratory failure with massive pulmonary infiltrates six weeks after
      coronary artery bypass operation.

PMID- 11344811
TI  - Management of recurrent infections in children.

PMID- 11344812
TI  - The elimination of smallpox from Israel.

PMID- 11344813
TI  - Hospital utilization and inpatient care.

PMID- 11344814
TI  - Disbelief or non-compliance of the elderly in influenza vaccination?

PMID- 11344815
TI  - Myopericarditis associated with streptococcal tonsilitis.

PMID- 11344816
TI  - The nose: just a matter of smell?

PMID- 11344817
TI  - Proteus mirabilis septic monoarthritis in a patient with CPDD.

PMID- 11344818
TI  - Prevalence of ischemic heart disease in patients with familial Mediterranean
      fever.
AB  - BACKGROUND: Familial Mediterranean fever is a genetic disorder manifested by
      recurrent attacks of peritonitis, pleuritis and arthritis, and characterized by
      clinical, histological and laboratory evidence for localized and systemic
      inflammation. Colchicine treatment usually prevents the attacks and the
      associated inflammation. Inflammation may play an important role in the
      initiation and progression of atherosclerosis and ischemic heart disease.
      OBJECTIVE: To study the effect of inflammation and its prevention on the
      occurrence of IHD, using FMF as a model. METHODS AND PATIENTS: We studied the
      presence of IHD and its risk factors in 290 FMF patients aged 40 years or more,
      and in two control groups--233 spouses of the FMF patients, and 126 patients with
      inflammatory diseases obtained from other outpatient clinics, FMF patients were
      also compared with age and gender-matched individuals from the population
      reference data of the Israel Ministry of Health. RESULTS: The prevalence of IHD
      in FMF patients was significantly lower than in the group of controls from other
      outpatient clinics (15.5% vs. 30.2%, P < 0.05) and comparable with their spouses
      (11.2%) and with the matched general population in Israel (16%). CONCLUSIONS:
      These findings suggest that despite the evidence of recurrent inflammation,
      colchicine-treated FMF patients are not more predisposed to IHD than the normal
      population.

PMID- 11344819
TI  - Gallstones: prevalence, diagnosis and treatment.

PMID- 11344820
TI  - Nerve and fibroblast growth factors as modulators of pancreatic beta cell
      plasticity and insulin secretion.
AB  - Trophic factors such as nerve and fibroblast growth factors are important
      modulators of beta cell physiology. These two factors induce the extension of
      neurite-like processes in primary cultures of adult rat beta cells. Moreover,
      both NGF and FGF enhance glucose-induced insulin secretion. Since beta cells
      synthesize NGF and pancreatic islet cells produce FGFs, it is possible that
      autocrine/paracrine interactions may be major regulators of insulin secretion,
      and impairment of these interactions could lead to pathological states such as
      diabetes mellitus.

PMID- 11344821
TI  - Intraarterial delivery of genetic vectors for the treatment of malignant brain
      tumors.
AB  - BACKGROUND: The transfer of therapeutic genes into malignant brain tumors has
      been the subject of intense preclinical and clinical research in recent years.
      Most approaches have used direct intratumoral placement of a variety of vectors
      and genes, such as retroviruses or adenoviruses carrying drug-susceptibility
      genes, modified replication-competent herpes virus, and several vectors carrying
      tumor suppressor genes such as the p53 gene. However, clinical results have so
      far been disappointing, mainly due to the limited ability to effectively
      distribute the genetic material into the target cell population. Accordingly,
      alternative delivery approaches into the central nervous system, e.g.,
      intravascular, are under investigation. Genetic vectors administered
      intravascularly are unlikely to penetrate the blood-brain barrier and transfer a
      gene into brain or tumor parenchyma. However, intravascular delivery of vectors
      may target endothelial cells lining the blood vessels of the brain. Since
      endothelial cells participate in a variety of physiological and pathological
      processes in the brain, their modulation by gene transfer may be used for a
      variety of therapeutic purposes. Angiogenically stimulated endothelial cells
      within tumors replicate rapidly and hence may become targets for retroviral
      mediated gene transfer. OBJECTIVE: To assess the anti-tumor effect of
      transferring a drug-susceptibility gene into endothelial cells of the tumor
      vasculature. METHODS: As a model for this approach we delivered concentrated
      retroviral vectors carrying a drug-susceptibility gene via the internal carotid
      artery of rats with malignant brain tumors. The safety and efficacy of this
      approach, without and with subsequent treatment with a pro-drug (ganciclovir),
      was evaluated. RESULTS: No acute or long-term toxicity was observed after
      intraarterial infusion of the vector. Treatment with ganciclovir resulted in
      variable hemorrhagic necrosis of tumors, indicating preferential transduction of
      the angiogenically stimulated tumor vasculature. This was accompanied by severe
      toxicity caused by subarachnoid hemorrhage and intracerebral hemorrhage in
      vascular territories shared by the tumor and adjacent brain. CONCLUSION: The data
      indicate that endothelial cells can be targeted by intraarterial delivery of
      retroviral vectors and can be used for devising new gene therapy strategies for
      the treatment of brain tumors.

PMID- 11344822
TI  - Penetration of autoantibodies into living cells, 2000.
AB  - The formerly prevalent concept that intact autoantibodies could not penetrate
      into viable cells has been defeated by a large amount of experimental findings
      and clinical observations that indicate otherwise. The penetration of
      autoantibodies into living cells seems to participate in the pathogenesis of
      diverse autoimmune diseases, but it may also play a physiological role in healthy
      individuals. Although the fine mechanisms of the phenomenon remain to be
      elucidated, the potential use of penetrating autoantibodies as vectors to deliver
      molecules into cells, with diverse therapeutic purposes, has gained growing
      interest during the last few years.

PMID- 11344823
TI  - The future of treatment for systemic lupus erythematosus.
AB  - The future promises good news for the treatment of systemic lupus erythematosus,
      some of which can already be foreseen. Increased knowledge on genes that
      participate in the predisposition, pathogenesis, pharmacogenetics of, and
      protection against this disease may permit intervention at this level. Also,
      better understanding about the role of sex hormones has allowed trials of weak
      androgens or prolactin inhibitors. New immunomodulators or immunosuppressors may
      enable more precise treatment at the immunoregulatory level, and greater
      knowledge on the disturbance of circuits has already provided hints and even
      allowed trials of anti-interleukin-10 antibodies, an IL-10 decreasing agent,
      tolerance-induction strategies or intervention at the level of T cell co
      stimulation, as well as immune ablation with subsequent stem cell
      transplantation. Autoantibodies can be removed, controlled by means of anti
      idiotypes, which are blocked from reaching their target antigen or uncoupled from
      the tissues they have reached. All these treatment strategies will gradually
      become decanted in order to achieve the optimal treatment of SLE, which may tum
      out to be its cure.

PMID- 11344824
TI  - Cytokine response and oxidative stress produced by ethanol, acetaldehyde and
      endotoxin treatment in HepG2 cells.
AB  - BACKGROUND: Inflammatory mediators, including cytokines and reactive oxygen
      species, are associated with the pathology of chronic liver disease. Hepatocytes
      are generally considered as targets but not producers of these important
      mediators. OBJECTIVES: To investigate whether cells of hepatocellular lineage are
      a potential source of various cytokines we estimated the expression and secretion
      of tumor necrosis factor alpha, transforming growth factor beta 1, and
      interleukins 1 beta, 6 and 8 in the culture of well-differentiated human HepG2
      cells treated for 24 hours with ethanol, acetaldehyde and lipopolysaccharide.
      Lipid peroxidation damage, glutathione content and glutathione peroxidase,
      catalase and superoxide dismutase activity were also determined. METHODS: HepG2
      cells were treated for 24 hours with ethanol (50 mM), acetaldehyde (175 microM)
      and LPS (1 microgram/ml). TNF-alpha, TGF-beta, IL-1 beta, IL-6 and IL-8 mRNA were
      determined by reverse transcriptase polymerase chain reaction and secretion by
      enzyme-linked immunoassay. Lipid peroxidation damage, glutathione content and
      antioxidant enzyme activities were determined spectrophotometrically. RESULTS:
      Exposure to ethanol for 24 hours induced the expression of TNF-alpha and TGF-beta
      1, secretion of IL-1 beta and TGF-beta 1 and decreased catalase activity.
      Acetaldehyde markedly increased TNF-alpha and IL-8 expression, stimulated IL-1
      beta and IL-8 secretion, increased lipid peroxidation damage and decreased
      catalase activity, while LPS exposure induced the expression of TNF-alpha, TGF
      beta 1, IL-6 and IL-8, the secretion of TGF-beta 1, IL-1 beta, IL-6 and IL-8, and
      a decrease in catalase activity. No change in GSH, GSHPx or SOD was found in any
      experimental condition. CONCLUSIONS: The present studies confirm and extend the
      notion that hepatocytes respond to ethanol, acetaldehyde and LPS-producing
      cytokines. Oxidative stress produced by the toxic injury plays an important role
      in this response through up-regulation of inflammatory cytokines.

PMID- 11344825
TI  - Effects of estrogen/medrogestone therapy on the apoprotein B-containing
      lipoproteins in postmenopausal women with type 2 diabetes mellitus under
      satisfactory and non-satisfactory glycemic control.
AB  - BACKGROUND: Information is lacking on the effects of hormone replacement therapy
      in women with diabetes, especially during moderate chronic hyperglycemia.
      OBJECTIVES: To study the effects of HRT on the lipid profile and the low density
      lipoprotein subclass distribution in women with type 2 diabetes under
      satisfactory and non-satisfactory glycemic control. METHODS: Fifty-four
      postmenopausal women after a 6 week run-in diet were randomized to receive either
      placebo (HbA1c < 8%, n = 13; HbA1c > 8%, n = 17) or HRT (HbA1c < 8%, n = 11;
      HbA1c > 8%, n = 13) for 12 weeks. HRT consisted of cyclical conjugated estrogens
      0.625 mg/day plus medrogestone 5 mg/day. At the beginning and at the end of each
      treatment period the LDL subclass distribution was estimated by density gradient
      ultracentrifugation. RESULTS: At the baseline and during the study, the HbA1c
      level was significantly higher in hyperglycemic patients than in the near
      normoglycemic controls (baseline 10.2 +/- 2.9 vs. 6.5 +/- 0.7%, P < 0.01). They
      showed a trend for higher total and LDL cholesterol, triglycerides and lower high
      density lipoprotein-cholesterol compared to near-normoglycemic controls, as well
      as significantly higher triglyceride concentrations in very low density
      lipoprotein, intermediate density lipoprotein and LDL-1 particles and cholesterol
      content in LDL-1 and -2 particles. HRT decreased LDL-cholesterol in both groups.
      In the normoglycemic patients a small increase in HbA1c was observed (6.5 +/- 0.7
      vs. 7.4 +/- 1%, P = 0.04). In all cases, HRT did not modify the proportion of LDL
      represented by denser LDLs. CONCLUSIONS: HRT did not modify the LDL subclass
      distribution, even in the presence of moderate chronic hyperglycemia in women
      with type 2 diabetes.

PMID- 11344826
TI  - The role of the hypothalamic neuropeptides hypocretin/orexin in the sleep-wake
      cycle.
AB  - The novel neuropeptides hypocretin/orexin have recently been located on the
      lateral hypothalamus cells. This system has been linked to the regulation of both
      feeding and sleep, and recent studies have found an association between a defect
      in these neuropeptides and narcolepsy. We conducted a MEDLINE review of all the
      articles published since the discovery of hypocretin/orexin peptides, narrowing
      the field to the relationship between these neuropeptides and sleep. The finding
      of a deletion in the transcription of the hypocretin receptor 2 gene in
      narcoleptic Doberman pinschers and the development of a knockout of the
      hypocretin gene in mice pointed to the relevance of this system in the sleep-wake
      cycle. We provide further evidence of the role of the hypocretin/orexin system in
      narcolepsy and in sleep regulation and present an integrative model of the
      pathophysiology of narcolepsy. The discovery of the link between these peptides
      and narcolepsy opens new avenues to both the understanding of sleep mechanisms
      and therapeutic implications for sleep disorders.

PMID- 11344827
TI  - Balneotherapy at the Dead Sea area for patients with psoriatic arthritis and
      concomitant fibromyalgia.
AB  - BACKGROUND: Balneotherapy has been successfully used to treat various rheumatic
      diseases, but has only recently been evaluated for the treatment of fibromyalgia.
      Since no effective treatment exists for this common rheumatic disease,
      complementary methods of treatment have been attempted. OBJECTIVES: To assess the
      effectiveness of balneotherapy at the Dead Sea area in the treatment of patients
      suffering from both fibromyalgia and psoriatic arthritis. METHODS: Twenty-eight
      patients with psoriatic arthritis and fibromyalgia were treated with various
      modalities of balneotherapy at the Dead Sea area. Clinical indices assessed were
      duration of morning stiffness, number of active joints, a point count of 18
      fibrositic tender points, and determination of the threshold of tenderness in
      nine fibrositic and in four control points using a dolorimeter. RESULTS: The
      number of active joints was reduced from 18.4 +/- 10.9 to 9 +/- 8.2 (P < 0.001).
      The number of tender points was reduced from 12.6 +/- 2 to 7.1 +/- 5 in men (P <
      0.003) and from 13.1 +/- 2 to 7.5 +/- 3.7 in women (P < 0.001). A significant
      improvement was found in dolorimetric threshold readings after the treatment
      period in women (P < 0.001). No correlation was observed between the reduction in
      the number of active joints and the reduction in the number of tender points in
      the same patients (r = 0.2). CONCLUSIONS: Balneotherapy at the Dead Sea area
      appears to produce a statistically significant substantial improvement in the
      number of active joints and tender points in both male and female patients with
      fibromyalgia and psoriatic arthritis. Further research is needed to elucidate the
      distinction between the benefits of staying at the Dead Sea area without
      balneotherapy and the effects of balneotherapy in the study population.

PMID- 11344828
TI  - Beta-carotene attenuates experimentally induced liver cirrhosis in rats.
AB  - OBJECTIVE: To study whether retinolpalmitate, beta-carotene or lycopene could
      prevent liver cirrhosis induced by thioacetamide in rats. METHODS: In the control
      group liver cirrhosis was induced in male Wistar rats by intraperitoneal
      injections of TAA 200 mg/kg for 12 weeks. The three study groups received in
      addition to TAA either beta-carotene, lycopene or retinopalmitate by gavage
      through an orogastric tube. Histopathological analysis and determination of the
      hydroxyproline contents of the livers were performed at the end of the protocol.
      RESULTS: Rats treated with beta-carotene and TAA had lower histopathologic scores
      and reduced levels of hepatic hydroxyproline (P = 0.02) than those treated by TAA
      alone. A trend of decreased fibrosis was observed in the rats treated with
      lycopene and TAA although this lacked statistical significance. CONCLUSIONS: Beta
      carotene attenuated liver cirrhosis induced by TAA in rats. The mechanism may be
      related to effects on hepatic stellate cells or to scavenging of free radicals by
      beta-carotene. Retinolpalmitate and lycopen had no significant beneficial effect.

PMID- 11344829
TI  - Acute cervical spinal cord injury, dopamine and venous hyperoxemia.

PMID- 11344831
TI  - An update on the genetics of systemic lupus erythematosus.
AB  - The development of systemic lupus erythematosus has a strong genetic basis. The
      techniques to study the genetics of SLE have improved, and family-based studies
      have been gaining importance due to advances in the human genome project.
      Recently, complete genome scans with microsatellite markers and linkage analysis
      have been performed in human systemic lupus erythematosus in various populations.
      These studies represent the first step of a process towards the identification of
      susceptibility genes in SLE. We review here the results of the human genome scans
      performed until now and provide an update of the latest advances on the genetics
      of SLE in linkage studies and association analyses of candidate genes.

PMID- 11344830
TI  - beta 2-glycoprotein I in human and murine atherosclerosis.

PMID- 11344832
TI  - Paraneoplastic syndromes associated with anti-Hu antibodies.
AB  - Paraneoplastic syndromes are disorders associated with cancer but without a
      direct effect of the tumor mass or its metastases on the nervous system. Small
      cell carcinoma of lung associated with paraneoplastic sensory neuronopathy and/or
      paraneoplastic encephalomyelitis with the presence of anti-Hu antibodies has been
      termed "anti-Hu syndrome." Anti-Hu associated PSN-PEM is an immune disorder in
      which both cell-mediated and humoral mechanisms are involved. Patients are
      considered affected by Anti-Hu associated PSN-PEM when they develop clinical
      signs and symptoms of CNS dysfunction and/or sensory neuropathy not caused by
      metastases or other disorders, and serum or cerebrospinal fluid is positive for
      Hu abs. SCLC is found in more than 90% of patients with cancer and positive Hu
      abs. Individual patients with Hu abs associated to SCLC may suffer PSN-PEM,
      limbic encephalitis, brainstem encephalopathy, opsoclonus-myoclonus,
      paraneoplastic cerebellar degeneration or myelopathy. Hu abs have a specificity
      of 99% and sensitivity of 82% in detecting paraneoplastic neurological syndromes.
      There are two types of treatment: the first is to treat the cancer, the second is
      to suppress the immune reaction with the use of corticosteroids,
      cyclophosphamide, azathioprine, plasma exchange, intravenous immunoglobulin and
      immunoadsorption; however, treatment of paraneoplastic syndromes is generally
      unsatisfactory.

PMID- 11344833
TI  - Homocysteine elevation with fibrates: is it a class effect?
AB  - BACKGROUND: Case-control and prospective studies indicate that an elevated plasma
      homocysteine level is a powerful risk factor for atherosclerotic vascular
      diseases. Certain medications can induce hyperhomocystinemia, such as
      methotrexate, trimethoprim and anti-epileptic drugs. There are few reports
      indicating an interaction between lipid-lowering drugs (cholestyramine and
      niacin) and homocysteine. Recently, an interaction was shown between fenofibrate
      and benzafibrates (a fibric acid derivative) and homocysteine plasma levels.
      OBJECTIVES: To evaluate the effects of different fibrates on plasma homocysteine
      levels and to measure the reversibility of this effect. METHODS AND RESULTS: We
      investigated the effects of ciprofibrate and bezafibrate on homocysteine levels
      in patients with type IV hyperlipidemia and/or low high density lipoprotein
      levels. While a 57% increase in homocysteine was detected in the ciprofibrate
      treated group (n = 26), a 17% reduction in homocysteine was detected in the group
      treated with bezafibrate (n = 12). The increase in homocysteine in the
      ciprofibrate-treated group was sustained for the 12 weeks of treatment and was
      partially reversible after 6 weeks of discontinuing the ciprofibrate therapy.
      CONCLUSIONS: These results indicate that an increase in plasma homocysteine
      levels following administration of fibrates is not a class effect, at least in
      its magnitude. Moreover, it is reversible upon discontinuation of the treatment.

PMID- 11344834
TI  - Abolition of pentagastrin-stimulated alkaline tide using the carbonic anhydrase
      inhibitor acetazolamide.
AB  - BACKGROUND: Alkaline tide is the transient increase in blood and urine pH
      following stimulation of gastric acid secretion. It is attributed to HCO3-
      release from parietal cells in parallel with H+ secretion. The enzyme carbonic
      anhydrase is thought to be responsible for HCO3- production from CO2 and OH- in
      the parietal cell. OBJECTIVE: To examine the effect of pretreatment with the
      carbonic anhydrase inhibitor, acetazolamide, on the alkaline tide phenomenon.
      METHODS: Ten patients with dyspepsia and demonstrable alkaline tide were tested
      on three separate days. The pH and base excess were determined in arterialized
      venous blood before and 45 minutes after an intramuscular injection of
      pentagastrin. The pH of the urine was measured before and 120 min after
      pentagastrin injection. Measurements were performed after pentagastrin alone on
      day 1, following pretreatment with acetazolamide 60 min before pentagastrin on
      day 2, and after the administration of acetazolamide alone on day 3. RESULTS:
      Following the administration of pentagastrin alone, the blood base excess
      increased by 1.61 +/- 0.2 mEq/L (mean +/- standard deviation) and the calculated
      alkaline tide at 45 min was 33.99 +/- 4.49 mEq. On day 2 with prior
      administration of acetazolamide, base excess decreased by 0.21 +/- 0.39 mEq/L,
      and the calculated alkaline tide was -3.28 +/- 7.57 mEq, which was significantly
      lower than on day 1 (P = 0.0001). On day 3, following acetazolamide alone, the
      base excess values decreased by 0.53 +/- 0.2 mEq/L and the alkaline tide was 
      10.05 +/- 3.33 mEq; there was no significant difference compared with day 2 (P =
      0.44). CONCLUSION: Pretreatment with acetazolamide abolished the alkaline tide
      induced by pentagastrin. This finding supports the view that carbonic anhydrase
      has a major role in the alkaline tide phenomenon.

PMID- 11344835
TI  - Treatment of Kaposi's sarcoma with vinblastine in patients with disseminated
      dermal disease.
AB  - BACKGROUND: Classic Kaposi's sarcoma is a rare tumor with an indolent behavior.
      Local therapy is not applicable in disseminated cutaneous disease. Patients with
      advanced disease are usually treated with systemic chemotherapy. OBJECTIVES: To
      assess the effectiveness and toxicity of single-agent vinblastine in the
      treatment of disseminated and recurrent Kaposi's sarcoma. METHODS: Ten patients
      with wide cutaneous spread of classic Kaposi's sarcoma were treated with single
      agent vinblastine, 6 mg/m2 intravenously once every 2 weeks. Vinblastine was
      continued for 2 months after achieving a maximal response. RESULTS: The
      male:female ratio was 2.3:1, and median age 64 years (range 50-79 years). The
      median number of involved nodules in the skin was 34. The overall response rate
      was 90%, 5 with complete response (50%) and 4 with partial response (40%).
      Complete responders had a longer duration of response than partial responders:
      41.2 vs. 14.8 months. The median survival of all patients was 33 months. Side
      effects were minimal and tolerable. CONCLUSIONS: Vinblastine is very effective in
      the treatment of extensive classic 'Kaposi's sarcoma, and results in a high
      response rate, long survival and disease-free survival with tolerable toxicity.

PMID- 11344836
TI  - Treatment of malignant astrocytomas with repetitive resections: a longitudinal
      study.
AB  - BACKGROUND: The impact of repeated surgical resection on the survivorship of
      patients with malignant astrocytomas is an issue of some controversy in the
      medical literature. OBJECTIVES: To clarify this issue through a retrospective
      analysis of treatment outcomes in a brain tumor clinic. METHODS: The patient
      records from the Brain Tumor Clinic at Hahnemann University Hospital for the
      period 1988 to 2000 were reviewed. From these, 112 cases of glioblastoma
      multiforme and 50 cases of anaplastic astrocytoma were chosen for analysis.
      RESULTS: The group of patients with glioblastomas showed a median survival of 415
      days. When analyzed as subgroups based on the number of surgical resections, the
      median survival was 393 days in the group with biopsy only, 380 days in the group
      with one surgical resection, and 548 days in the group with two or three
      resections. Using the Kaplan-Meier method to generate survival plots and the log
      rank test to compare groups, repeat debulking was found to be a significant
      predictor of survival (P = 0.173). The group of patients with anaplastic
      astrocytomas showed a median survival of 1,311 days. When analyzed by subgroups,
      the patients with biopsy only had a median survival of 544 days, those with one
      debulking 1,589 days and those with two or three debulkings 1,421 days. There was
      a trend toward increased survival with debulking and the log rank test again
      showed statistical significance (P = 0.1998). CONCLUSIONS: This study indicates
      that repeated surgical resections offer increased survival for both glioblastomas
      and anaplastic astrocytomas.

PMID- 11344837
TI  - The postnatal management of congenital cystic adenomatoid malformation.
AB  - BACKGROUND: Routine prenatal ultrasound has increased the frequency of prenatal
      diagnosis of congenital cystic lung malformation, such as cystic adenomatoid
      malformation, pulmonary sequestration, congenital lobar emphysema, and
      bronchogenic cyst. OBJECTIVES: To evaluate the methods of postnatal diagnosis,
      the optimal age for operation since surgery is always required, and the optimal
      extent of lung resection. METHODS: The clinical courses of 11 patients with
      congenital lung cysts who underwent surgical lung resection (8 lobectomies and 3
      segmentectomies) were reviewed. RESULTS: The diagnosis was confirmed by computed
      tomography scan in all. In nine patients the diagnosis was made prenatally. Chest
      X-ray was normal postnatally in all patients except for two who had recurrent
      pneumonia. Postoperative follow-up showed excellent recovery in all operated
      children. One patient who underwent surgery for CCAM following episodes of severe
      pneumonia died from another cause 5 months later. Postoperative chest CT scan
      showed no residual disease in eight patients. In two who had undergone limited
      resection, tomography showed a small segment of residual disease in one and a
      suspected residual lesion in the other. CONCLUSION: With prenatal ultrasound the
      true frequency of congenital cystic lung anomaly appears to be higher than
      previously reported. Postnatal CT is mandatory to confirm or to rule out the
      diagnosis. The mere presence of cystic lung malformation is an indication for
      surgery. Complete removal of the affected lung lobe is recommended. Segmental
      resection may be inadequate. Early operation is tolerated well by infants and
      small children and we recommend that surgery be performed in children between 6
      and 12 months of age.

PMID- 11344838
TI  - Perforated appendicitis in the child: contemporary experience.
AB  - BACKGROUND: Despite years of research and clinical experience with acute
      appendicitis, the rate of complications in the pediatric age group continues to
      be high. OBJECTIVE: To characterize the profile of the child with appendicitis
      complicated by perforation or intraabdominal abscess. METHODS: Between 1 January
      1985 and 31 December 1997 in our department, 581 children under the age of 14
      years were clinically diagnosed as suffering from "acute appendicitis." The final
      diagnoses were: while appendix in 28 cases (4.8%), acute non-complicated
      appendicitis in 472 (81%), and complicated appendicitis in 81 (13.9%), including
      51 cases of free perforation (8.7%) and 30 cases of intraabdominal abscess
      (5.2%). We retrospectively reviewed the charts of all children with complicated
      appendicitis and those of 70 randomly selected children with non-complicated
      appendicitis, and compared patient age, gender, weight percentile, past medical
      history, and course of the illness. RESULTS: The children with complicated
      appendicitis were significantly younger (P = 4.8 x 10(-7)), they had higher oral
      and rectal temperatures (P = 7.9 x 10(-8)), higher platelet count (P = 0.0008)
      and lower hemoglobin level (P = 0.004). No difference was found in white blood
      count (P = 0.41). Total delay from symptom onset to surgery was 33 hours (SD 23)
      in the non-complicated group, 60 hours (SD 38) in the perforated appendicitis
      group, and 176 hours (SD 107) in the intraabdominal abscess group (P = 4.6 x 10(
      8)). No difference in intra-hospital delay was found. CONCLUSIONS: Children with
      complicated appendicitis are characterized by younger age, longer delay from
      symptom onset to correct diagnosis, and typical laboratory findings. Delays in
      diagnosis can be avoided by first considering the diagnosis of acute appendicitis
      in the differential diagnosis when examining any child with abdominal pain.

PMID- 11344839
TI  - Antimicrobial susceptibility testing for Helicobacter pylori: implications for
      clinical practice.

PMID- 11344840
TI  - Calcium--an "all-round player" in the cornea.

PMID- 11344841
TI  - Laboratory diagnostics in vasculitis patients.
AB  - Anti-neutrophil cytoplasm antibodies are important markers of certain small
      vessel necrotizing vasculitides, but the optimal use of laboratory results in
      daily clinical practice necessitates collaboration between clinicians and
      laboratory specialists. Physicians must familiarize themselves with ANCA tests in
      ANCA-related vasculitides as well as in differential diagnostic patient
      populations in order to define cutoff values. Indirect immunofluorescence with a
      consensus-agreed technique combined with standardized enzyme immunoassays is the
      modality for detecting the main SSV-associated ANCA specificities using cutoff
      values that can sufficiently distinguish SVV from non-SVV patients. The combined
      use of IIF and direct EIA to demonstrate proteinase 3-ANCA and myeloperoxidase
      ANCA at significant levels leads to a very high diagnostic specificity towards
      SVV conditions such as Wegener's granulomatosis, microscopic polyangiitis, Churg
      Strauss syndrome, and limited forms of these such as renal-limited focal
      necrotizing glomerulonephritis. A strong reactivity of ANCA against several
      azurophil granule components indicates a drug-induced syndrome. ANCA-related SVV
      and drug-induced vasculitis or lupus syndromes have characteristic ANCA profiles
      that can help distinguish these conditions from other inflammatory diseases.

PMID- 11344842
TI  - From 5 fluorouracil to the new oral fluoropyrimidines: a brief overview of four
      decades of clinical investigations.

PMID- 11344843
TI  - Mitral valve prolapse and thromboembolic events.

PMID- 11344844
TI  - Cough syncope with herpetic tracheobronchitis.

PMID- 11344845
TI  - "Cyanotic blue tongue" in severe rheumatic tricuspid regurgitation.

PMID- 11344846
TI  - Primary neuroendocrine tumor (carcinoid) of the mesocolon.

PMID- 11344847
TI  - Echinococcosis of the spleen during pregnancy.

PMID- 11344848
TI  - The use of microarrays in medicine.

PMID- 11344849
TI  - Monitored anesthesia care in awake craniotomy for brain tumor surgery.

PMID- 11344850
TI  - Perirenal fixation of an aortic stent graft in a chronic hemodialysis patient.

PMID- 11344851
TI  - An unusual cause of abdominal discomfort.

PMID- 11344852
TI  - Lord Immanuel Jakobovits: grandfather of Jewish medical ethics.

PMID- 11344853
TI  - The evolving management of penetrating neck injuries.

PMID- 11344854
TI  - "Will for equal opportunity stronger than the wish to die?".

PMID- 11344855
TI  - Moses Maimonides was born in 1138, not 1135 C.E.

PMID- 11344856
TI  - The application of infliximab (Remicade), a chimeric monoclonal antibody, in the
      treatment of rheumatic diseases.

PMID- 11344857
TI  - CpG DNA modulation of allergic asthma.

PMID- 11344859
TI  - Analysis of recombinant human alpha 1 integrin I-domain with a function-blocking
      monoclonal antibody, 1B3.1.

PMID- 11344858
TI  - Interleukin-18 and allergic asthma.

PMID- 11344860
TI  - Molecular mimicry: lessons from an experimental model of antiphospholipid
      syndrome in naive mice.

PMID- 11344861
TI  - Interleukin-17 may have a central role in inflammatory joint diseases as a "fine
      tuning" cytokine.

PMID- 11344862
TI  - Dysautonomia in chronic fatigue syndrome vs. fibromyalgia.

PMID- 11344863
TI  - Pathogenic anti-endothelial cell antibodies: classification to anti-microvascular
      EC and anti-macrovascular EC antibodies.

PMID- 11344864
TI  - Cytokine production and matrix metalloproteinase (MMP)-9 release by human mast
      cells following cell-to-cell contact with activated T cells.

PMID- 11344865
TI  - Immunosuppressants in systemic vasculitides.

PMID- 11344866
TI  - Rheumatology--past, present and future.

PMID- 11344867
TI  - Primary biliary cirrhosis and autoimmunity: evaluating the genetic risk.
AB  - The genetic basis of autoimmunity is receiving increased attention. Organ
      specific diseases, such as primary biliary cirrhosis, may be considered model
      diseases to use for development of databases and extrapolation to other
      autoimmune diseases. PBC is an enigmatic autoimmune disease that predominantly
      affects females and leads to destruction of intrahepatic bile ducts. The
      serologic hallmark of this disease is anti-mitochondrial antibodies that
      specifically react with the E2 components of 2-oxodehydrogenase enzymes,
      including PDC-E2. There are no clear major histocompatibility complex
      associations with the development of PBC, despite the observation that first
      degree relatives of index patients with PBC have a 4-6% prevalence of development
      of PBC. This risk factor is comparable or higher than any other human autoimmune
      disease and suggests that a genome-wide approach towards dissection of genetic
      associations would lead to valuable new insights. In this review we place these
      concepts in perspective and highlight in particular the genetic associations in
      primary biliary cirrhosis.

PMID- 11344868
TI  - "Salus Populi Suprema Lex": the health of the people is the supreme law.

PMID- 11344869
TI  - A new paradigm for HIV care: ethical and clinical considerations.
AB  - Although dramatic advances in clinical treatment have greatly improved the lives
      of many people with HIV/AIDS, many other patients do not have information about
      or access to these treatments because of health care providers' presumptive
      judgments about patients' ability to adhere to medical regimens. The authors
      contend that with sufficient support and education most patients, even those with
      difficult social and medical problems, can be helped to initiate and maintain HIV
      treatment in accordance with current clinical standards. This commentary
      delineates a new paradigm for HIV care in which patients and providers
      collaborate on individualized plans to establish patients' readiness for
      treatment, ensure maintenance of treatment, and make use of the social services
      necessary to accomplish these goals. Providers have an ethical responsibility to
      do everything possible to see that patients who might benefit from new HIV
      treatments have a fair opportunity to do so, and health systems have a
      responsibility to facilitate this process. Substantial progress toward meeting
      these responsibilities can be made within the current health care environment.

PMID- 11344870
TI  - Vieques, Puerto Rico: an island under siege.

PMID- 11344871
TI  - Syringe prescription to prevent HIV infection in Rhode Island: a case study.
AB  - Injection drug users (IDUs) are a population at high risk for many diseases,
      including AIDS, and are clearly in need of medical and substance abuse treatment.
      Access to sterile syringes is critical for lowering the risk of transmission of
      HIV and other blood-borne pathogens among IDUs. Previously tried strategies
      include needle exchange programs and changing laws to allow the legal purchase
      and possession of syringes. An alternative strategy is to have physicians
      prescribe syringes to IDUs. To the best of our knowledge, this has previously
      been tried by only a few physicians in rare situations and never on a
      programmatic basis. This report describes the genesis of physician's syringe
      prescription in Rhode Island and some of the lessons learned to date. Because of
      the illicit nature of drug use, a tremendous amount of mistrust and fear on the
      part of IDUs often leads to poor interaction with the medical establishment.
      Prescription of syringes by a physician can serve as a tool for reaching out to a
      high-risk and often out-of-treatment population of drug users. It is a way for
      the health care community to tap into drug-using networks and bring those
      populations into a medical care system.

PMID- 11344872
TI  - Keeping the M in MTCT: women, mothers, and HIV prevention.

PMID- 11344873
TI  - Where is the M in MTCT? The broader issues in mother-to-child transmission of
      HIV.

PMID- 11344874
TI  - Syphilis control during pregnancy: effectiveness and sustainability of a
      decentralized program.
AB  - OBJECTIVES: This study sought to assess the performance, effectiveness, and costs
      of a decentralized antenatal syphilis screening program in Nairobi, Kenya.
      METHODS: Health clinic data, quality control data, and costs were analyzed.
      RESULTS: The rapid plasma reagin (RPR) seroprevalence was 3.4%. In terms of
      screening, treatment, and partner notification, the program's performance was
      adequate. The program's effectiveness was problematic because of false-negative
      and false-positive RPR results. The cost per averted case was calculated to be
      US$95 to US$112. CONCLUSIONS: The sustainability of this labor-intensive program
      is threatened by costs and logistic constraints. Alternative strategies, such as
      the mass epidemiologic treatment of pregnant women in high-prevalence areas,
      should be considered.

PMID- 11344875
TI  - Terrorism, biological weapons, and bonanzas: assessing the real threat to public
      health.

PMID- 11344877
TI  - Good intentions and the road to bioterrorism preparedness.

PMID- 11344876
TI  - Hospital preparedness for victims of chemical or biological terrorism.
AB  - OBJECTIVES: This study examined hospital preparedness for incidents involving
      chemical or biological weapons. METHODS: By using a questionnaire survey of 224
      hospital emergency departments in 4 northwestern states, we examined
      administrative plans, training, physical resources, and representative medication
      inventories. RESULTS: Responses were received from 186 emergency departments
      (83%). Fewer than 20% of respondent hospitals had plans for biological or
      chemical weapons incidents. About half (45%) had an indoor or outdoor
      decontamination unit with isolated ventilation, shower, and water containment
      systems, but only 12% had 1 or more self-contained breathing apparatuses or
      supplied air-line respirators. Only 6% had the minimum recommended physical
      resources for a hypothetical sarin incident. Of the hospitals providing
      quantitative answers about medication inventories, 64% reported sufficient
      ciprofloxacin or doxycycline for 50 hypothetical anthrax victims, and only 29%
      reported sufficient atropine for 50 hypothetical sarin victims (none had enough
      pralidoxime). CONCLUSIONS: Hospital emergency departments generally are not
      prepared in an organized fashion to treat victims of chemical or biological
      terrorism. The planned federal efforts to improve domestic preparedness will
      require substantial additional resources at the local level to be truly
      effective.

PMID- 11344878
TI  - Biological and chemical terrorism defense: a view from the "front lines" of
      public health.

PMID- 11344879
TI  - Preemptive biopreparedness: can we learn anything from history?
AB  - The treat of bioterrorism is in the public eye again, and major public health
      agencies are urging preparedness efforts and special federal funding. In a sense,
      we have seen this all before. The Centers for Disease Control and Prevention grew
      substantially during the Cold War era in large part because Alexander Langmuir,
      Chief Epidemiologist of the CDC, used an earlier generation's anxieties to
      revitalize the CDC, create an Epidemic Intelligence Service, and promote
      epidemiologic "surveillance" as part of the nation's defense. Retrospective
      investigation suggests that, while Langmuir contributed to efforts promoted by
      the Department of Defense and the Federal Civil Defense Administration, the
      United States did not have real cause to fear Communist biological warfare
      aggression. Given clear historical parallels, it is appropriate to ask, What was
      gained and what was lost by Langmuir's central role in that first instance of
      American biopreparedness? Among the conclusions drawn is that biopreparedness
      efforts fed the Cold War climate, narrowed the scope of public health activities,
      and failed to achieve sustained benefits for public health programs across the
      country.

PMID- 11344880
TI  - Barriers to universal prenatal HIV testing in 4 US locations in 1997.
AB  - OBJECTIVES: We determined rates of prenatal HIV testing and investigated barriers
      to testing. METHODS: We surveyed 1362 representative parturient women from 7
      hospitals in 4 locations of the United States. RESULTS: Overall, 89.9% of women
      reported being offered HIV testing and 69.6% reported being tested. Proportions
      of women not offered testing differed by location (range = 5.2%-16.3%), as did
      proportions not tested (range = 12.2%-54.4%). Among women who perceived that
      their clinicians had not recommended testing, 41.7% were tested, compared with
      92.8% of women who perceived a strong recommendation (P < .05). Private insurance
      for prenatal care was also associated with not being tested. Women gave multiple
      reasons for not being tested, most commonly not being at risk, having been tested
      recently, and the test's not being offered or recommended, cited by 55.3%, 39.1%
      and 11.1% of women, respectively. CONCLUSIONS: Although most parturient women
      were offered a prenatal HIV test and got tested, testing proportions did not
      reach national goals and differed significantly by location and payment status.
      Concern about testing consequences was not a major barrier. Perception of
      clinicians' recommendations strongly influenced testing. Changing provider
      practices will be essential to implementing universal prenatal HIV testing.

PMID- 11344881
TI  - Zip code-level risk factors for tuberculosis: neighborhood environment and
      residential segregation in New Jersey, 1985-1992.
AB  - OBJECTIVES: This study examined zip code-level risk factors associated with very
      high tuberculosis (TB) rates among non-Hispanic Whites, African Americans,
      Hispanics, and Asians in New Jersey (1985-1992). METHODS: Exposure indices
      (poverty, crowded housing, and dilapidated housing) and segregation indices
      (contact with immigrants, isolation, and density) were used to characterize zip
      codes. A Boolean-logic methodology was used to determine which configurations of
      risk factors significantly distinguish zip codes where TB rates are very high
      from other zip codes. RESULTS: For Whites and Asians, risk factors were rare in
      zip codes with very high TB rates. In agreement with the distribution of TB cases
      by age and foreign-born status, this suggests that cases among Whites may be
      caused by reactivation, whereas cases among Asians may be imported. In contrast,
      Hispanics and African Americans were exposed to risk factors that may facilitate
      TB transmission. Among Hispanics, high contact with immigrants was an important
      factor. African Americans were the group most frequently exposed to multiple risk
      factors. CONCLUSIONS: For Hispanics and African Americans, zip code-level risk
      factors were associated with very high TB rates.

PMID- 11344882
TI  - Evaluation of indicated suicide risk prevention approaches for potential high
      school dropouts.
AB  - OBJECTIVES: This study evaluated the efficacy of 2 indicated preventive
      interventions, postintervention and at 9-month follow-up. METHODS: Drawn from a
      pool of potential high school dropouts, 460 youths were identified as being at
      risk for suicide and participated in 1 of 3 conditions randomly assigned by
      school: (1) Counselors CARE (C-CARE) (n = 150), a brief one-to-one assessment and
      crisis intervention; (2) Coping and Support Training (CAST) (n = 155), a small
      group skills-building and social support intervention delivered with C-CARE; and
      (3) usual-care control (n = 155). Survey instruments were administered pre
      intervention, following C-CARE (4 weeks), following CAST (10 weeks), and at a 9
      month follow-up. RESULTS: Growth curve analyses showed significant rates of
      decline in attitude toward suicide and suicidal ideation associated with the
      experimental interventions. C-CARE and CAST, compared with usual care, also were
      effective in reducing depression and hopelessness. Among females, reductions in
      anxiety and anger were greater in response to the experimental programs. CAST was
      most effective in enhancing and sustaining personal control and problem-solving
      coping for males and females. CONCLUSIONS: School-based, indicated prevention
      approaches are feasible and effective for reducing suicidal behaviors and related
      emotional distress and for enhancing protective factors.

PMID- 11344883
TI  - Child sexual abuse and subsequent psychopathology: results from the National
      Comorbidity Survey.
AB  - OBJECTIVES: This study examined the relationship between child sexual abuse (CSA)
      and subsequent onset of psychiatric disorders, accounting for other childhood
      adversities, CSA type, and chronicity of the abuse. METHODS: Retrospective
      reports of CSA, other adversities, and psychiatric disorders were obtained by the
      National Comorbidity Survey, a nationally representative survey of the United
      States (n = 5877). Reports were analyzed by multivariate methods. RESULTS: CSA
      was reported by 13.5% of women and 2.5% of men. When other childhood adversities
      were controlled for, significant associations were found between CSA and
      subsequent onset of 14 mood, anxiety, and substance use disorders among women and
      5 among men. In a subsample of respondents reporting no other adversities, odds
      of depression and substance problems associated with CSA were higher. Among
      women, rape (vs molestation), knowing the perpetrator (vs strangers), and
      chronicity of CSA (vs isolated incidents) were associated with higher odds of
      some disorders. CONCLUSIONS: CSA usually occurs as part of a larger syndrome of
      childhood adversities. Nonetheless, CSA, whether alone or in a larger adversity
      cluster, is associated with substantial increased risk of subsequent
      psychopathology.

PMID- 11344884
TI  - Depression and substance use in minority middle-school students.
AB  - OBJECTIVES: This study investigated the association between depression and
      substance use in a sample of middle-school students. METHODS: The 5721 students
      (59%-63% Hispanic) completed self-report items on depressive symptoms, recent
      smoking and binge drinking, and lifetime use of marijuana, cocaine, and
      inhalants. RESULTS: Symptoms of depression were strongly and positively related
      to substance use. For every type of use, a stepwise increase was seen between the
      percentage of students with low symptom frequency and the percentage of students
      with more symptoms. A sizable number of users reported symptoms indicating major
      depression. Depression scores showed few clinically meaningful differences among
      demographic subgroups. Substance use scores, in contrast, showed meaningful
      intergroup differences for racial/ethnic group and other demographic variables.
      CONCLUSIONS: Depressive symptoms and substance use were associated in a sample of
      middle-school students who were largely non-White and predominantly Hispanic.
      Greater understanding of the nature of this association is needed; this
      understanding should be used to design prevention programs, and prevention
      programs should be introduced at least in the middle-school years.

PMID- 11344885
TI  - Use of antiretroviral therapies among HIV-infected men who have sex with men: a
      household-based sample of 4 major American cities.
AB  - OBJECTIVES: This study sought to determine the prevalence and determinants of use
      of recommended antiretroviral regimens among urban seropositive men who have sex
      with men (MSM). METHODS: A probability telephone sample of MSM was taken within
      regions of Chicago, Los Angeles, New York, and San Francisco. Analysis focused on
      use of antiretroviral therapies. RESULTS: Although the majority of seropositive
      MSM with CD4 counts below 500 per microliter were using recommended
      antiretroviral regimens, 26% of seropositive MSM were not receiving such care.
      Men who were younger, who reported a sexual orientation other than homosexual,
      who had a more recent interview date, who were at middle levels of affiliation
      with the gay community, and who reported higher levels of perceived exclusivity
      on the part of the gay community were less likely to be using recommended
      antiretroviral regimens. CONCLUSIONS: Although current efforts to make
      antiretroviral therapies available to HIV-seropositive MSM are reasonably
      effective, additional efforts are needed for MSM characterized by relative youth
      and lower social support.

PMID- 11344886
TI  - The impact of harm-reduction-based methadone treatment on mortality among heroin
      users.
AB  - OBJECTIVES: The purpose of this study was to investigate the impact of harm
      reduction-based methadone programs on mortality among heroin users. METHODS: A
      prospective cohort investigation was conducted among 827 participants in the
      Amsterdam Cohort Study. Poisson regression was used to identify methadone
      maintenance treatment characteristics (dosage, frequency of program attendance,
      and type of program) that are significantly and independently associated with
      mortality due to natural causes and overdose. RESULTS: From 1985 to 1996, 89
      participants died of natural causes, and 31 died as a result of an overdose.
      After adjustment for HIV and underweight status, there was an increase in natural
      cause mortality among subjects who left methadone treatment (relative risk [RR] =
      2.38, 95% confidence interval [CI] = 1.28, 4.55). Leaving treatment was also
      related to higher overdose mortality, but only among injection drug users (RR =
      4.55, 95% CI = 1.89, 10.00). CONCLUSIONS: Harm-reduction-based methadone
      treatment, in which the use of illicit drugs is tolerated, is strongly related to
      decreased mortality from natural causes and from overdoses. Provision of
      methadone in itself, together with social-medical care, appears more important
      than the actual methadone dosage.

PMID- 11344888
TI  - A seat at the table: membership in federal advisory committees evaluating public
      policy in genetics.
AB  - OBJECTIVES: This study examined who participates in federal government advisory
      committees regarding public policy in human and medical genetics, what parties
      they represent, and to what extent the general public is meaningfully
      represented. METHODS: Analysis focused on 7 federal government documents
      published from January 1990 to February 1995. Advisors were categorized into 4
      groups based on the professional affiliations that were listed in the
      publications. After a search of several references and data-bases, the study
      examined whether these individuals also had other affiliations not listed in the
      government publications. RESULTS: Individuals whose principal affiliations were
      with academia (n = 32; 44%) or industry (n = 19; 26%) represented nearly three
      fourths of the sample, followed by government employees (n = 13; 18%) and
      consumer advocates (n = 8; 11%). At least 16% of the advisors serving on the
      federal committees, mostly members of academia, had a dual affiliation.
      CONCLUSIONS: These data indicate that the public has modest representation on key
      federal advisory committees making policy recommendations regarding human
      genetics technology and clinical practice and that there is ample room for
      additional public participation.

PMID- 11344887
TI  - Food insufficiency, family income, and health in US preschool and school-aged
      children.
AB  - OBJECTIVES: This study investigated associations between family income, food
      insufficiency, and health among US preschool and school-aged children. METHODS:
      Data from the third National Health and Nutrition Examination Survey were
      analyzed. Children were classified as food insufficient if the family respondent
      reported that the family sometimes or often did not get enough food to eat.
      Regression analyses were conducted with health measures as the outcome variables.
      Prevalence rates of health variables were compared by family income category,
      with control for age and gender. Odds ratios for food insufficiency were
      calculated with control for family income and other potential confounding
      factors. RESULTS: Low-income children had a higher prevalence of poor/fair health
      status and iron deficiency than high-income children. After confounding factors,
      including poverty status, had been controlled, food-insufficient children were
      significantly more likely to have poorer health status and to experience more
      frequent stomachaches and headaches than food-sufficient children; preschool food
      insufficient children had more frequent colds. CONCLUSIONS: Food insufficiency
      and low family income are health concerns for US preschool and school-aged
      children.

PMID- 11344889
TI  - Laws prohibiting over-the-counter syringe sales to injection drug users:
      relations to population density, HIV prevalence, and HIV incidence.
AB  - OBJECTIVES: This study sought to assess relations of laws prohibiting over-the
      counter syringe sales (anti-OTC laws) to population prevalence of injection drug
      users and HIV prevalence or incidence among 96 US metropolitan areas. METHODS: A
      cross-sectional analysis was used. RESULTS: Metropolitan areas with anti-OTC laws
      had a higher mean HIV prevalence (13.8% vs 6.7%) than other metropolitan areas
      (pseudo-P < .001). In 83 metropolitan areas with HIV prevalence of less than 20%,
      anti-OTC laws were associated with HIV incidence rates of 1% or greater (pseudo-P
      < .001). Population proportions of injection drug users did not vary by presence
      of anti-OTC laws. CONCLUSIONS: Anti-OTC laws are not associated with lower
      population proportions of injection drug users. Laws restricting syringe access
      are associated with HIV transmission and should be repealed.

PMID- 11344890
TI  - Recency of immigration, substance use, and sexual behavior among Massachusetts
      adolescents.
AB  - OBJECTIVES: This study examined the relationships between recency of immigration,
      substance use, and sexual behavior. METHODS: Surveys were conducted with 2635
      Massachusetts 8th and 10th graders that allowed comparisons of health behaviors
      and risk and protective factors among students living in the United States
      "always," more than 6 years, or 6 years or less. RESULTS: Compared with lifetime
      residents, immigrant youths (particularly those living in the United States 6
      years or less) reported lower lifetime and recent alcohol and marijuana use (P <
      .001); sexual intercourse rates were similar across groups. However, recent
      immigrants were most likely to report peer pressures to engage in, and less
      parental support to avoid, risk behaviors (P < .001). CONCLUSIONS: A window of
      opportunity exists to provide primary prevention programs in schools to immigrant
      youths that may reduce adolescent health risk behaviors.

PMID- 11344891
TI  - Women in jail: is substance abuse treatment enough?
AB  - OBJECTIVES: This study examined the self-reported needs of women in jail who
      indicated a need for drug abuse services. METHODS: A total of 165 interviews were
      conducted of women held in a large, urban county jail in Ohio in May 1999.
      RESULTS: Drug-abusing women were more likely to report a need for housing, mental
      health counseling, education, job training, medical care, family support, and
      parenting assistance when released from jail. CONCLUSIONS: The provision of drug
      abuse treatment referrals to women in jail may not break the continual cycle of
      drug use and incarceration if other needs cannot be addressed.

PMID- 11344892
TI  - Lowered legal blood alcohol limits for young drivers: effects on drinking,
      driving, and driving-after-drinking behaviors in 30 states.
AB  - OBJECTIVES: This study evaluated the effects on drinking and driving of lowered
      allowable blood alcohol concentration (BAC) limits for drivers younger than 21
      years in 30 US states between 1984 and 1998. METHODS: Outcome measures were based
      on self-reports from a cross-sectional sample of more than 5000 high school
      seniors in 30 states surveyed before and after BAC limits were implemented in
      their states. RESULTS: Frequency of driving after any drinking and driving after
      5 or more drinks declined 19% and 23%, respectively. Lower BAC limits did not
      affect overall amount of drinking or total number of miles driven. CONCLUSIONS:
      Significant beneficial effects of lowered youth BAC limits have appeared despite
      limited publicity and enforcement of the new laws.

PMID- 11344893
TI  - Racial/ethnic differences in attitudes toward seeking professional mental health
      services.
AB  - OBJECTIVES: This study examined racial/ethnic differences in attitudes toward
      seeking mental health services. METHODS: Data from the National Comorbidity
      Survey, which administered a structured diagnostic interview to a representative
      sample of the US population (N = 8098), were analyzed. Multiple logistic
      regression was used, and data were stratified by need for mental health services.
      RESULTS: African Americans with depression were more likely than Whites with
      depression to "definitely go" (odds ratio [OR] = 1.8, P < .001) seek mental
      health services. African Americans with severe psychiatric disorders were less
      likely to be "somewhat embarrassed if friends knew they sought care" (OR = 0.3, P
      < .001) than were their White counterparts. CONCLUSIONS: African Americans
      reported more positive attitudes toward seeking mental health services than did
      Whites.

PMID- 11344894
TI  - Unintended pregnancy and low birthweight in Ecuador.
AB  - OBJECTIVES: This study assessed the relationship between unintended pregnancy and
      infant birthweight in Ecuador, differentiating between unwanted and mistimed
      pregnancies. METHODS: Analyses focused on a subsample of women (n = 2490)
      interviewed in the 1994 Ecuador Demographic and Maternal-Child Health Survey.
      Logistic regression was used to assess the relationship between pregnancy
      intention status and low birthweight after control for other factors. RESULTS:
      Infants from unwanted pregnancies were more likely than infants from planned
      pregnancies to have low birthweight (odds ratio = 1.64, 95% confidence interval =
      1.22, 2.20). Mistimed pregnancy was not associated with low birthweight.
      CONCLUSIONS: Unwanted pregnancy, but not mistimed pregnancy, is associated with
      low birthweight in Ecuador. Further research is needed to understand the
      mechanism through which pregnancy intention status affects birthweight.

PMID- 11344895
TI  - Community assessment in a vertically integrated health care system.
AB  - OBJECTIVES: In this report, the authors present a representative case of the
      implementation of community assessment and the subsequent application of findings
      by a large, vertically integrated health care system. METHODS: Geographic
      information systems technology was used to access and analyze secondary data for
      a geographically defined community. Primary data included a community survey and
      asset maps. RESULTS: In this case presentation, information has been collected on
      demographics, prevalent health problems, access to health care, citizens'
      perceptions, and community assets. The assessment has been used to plan services
      for a new health center and to engage community members in health promotion
      interventions. CONCLUSIONS: Geographically focused assessments help target
      specific community needs and promote community participation. This project
      provides a practical application for integrating aspects of medicine and public
      health.

PMID- 11344896
TI  - Subgroup-specific effects of questionnaire wording on population-based estimates
      of mammography prevalence.
AB  - OBJECTIVES: This study investigated whether an apparent downturn in prevalence
      rates of mammography use reported in the 1992 Behavioral Risk Factor Surveillance
      System (BRFSS) questionnaire resulted from a change in questionnaire wording.
      METHODS: In a pretest-posttest design (1990-1991 vs 1992), piecewise linear
      regression analyses were based on monthly prevalence estimates of mammography use
      among female BRFSS respondents 40 years or older. RESULTS: Self-reported
      mammography use was lower by 3.5 percentage points (95% confidence interval [CI]
      = 1.5, 5.5) overall--and lower by 13.6 percentage points (95% CI = 2.6, 24.6)
      among Black women with less than a high school education--when predicted from
      1992 data than when predicted from 1990-1991 data. CONCLUSIONS: A change in
      questionnaire wording in the BRFSS caused demographic-specific effects in
      population-based estimates of mammography use.

PMID- 11344898
TI  - A terse amendment produces broad change in data access.

PMID- 11344897
TI  - An assessment of the ability of routine restaurant inspections to predict food
      borne outbreaks in Miami-Dade County, Florida.
AB  - OBJECTIVES: This study sought to determine the usefulness of restaurant
      inspections in predicting food-borne outbreaks in Miami-Dade County, Fla.
      METHODS: Inspection reports of restaurants with outbreaks in 1995 (cases; n = 51)
      were compared with those of randomly selected restaurants that had no reported
      outbreaks (controls; n = 76). RESULTS: Cases and controls did not differ by
      overall inspection outcome or mean number of critical violations. Only 1 critical
      violation--evidence of vermin--was associated with outbreaks (odds ratio = 3.3;
      95% confidence interval = 1.1, 13.1). CONCLUSIONS: Results of restaurant
      inspections in Miami-Dade County did not predict outbreaks. If these findings are
      representative of the situation in other jurisdictions, inspection practices may
      need to be updated.

PMID- 11344899
TI  - Cost-benefit analysis of urine pregnancy tests prior to menstrual regulation in
      Vietnam.

PMID- 11344900
TI  - Methods in survey research: evidence for the reliability of group administration
      vs personal interviews.

PMID- 11344901
TI  - Tobacco supply control program.

PMID- 11344902
TI  - [Science in diabetes mellitus].
AB  - The Citizen Joint Symposium on "Science in Diabetes Mellitus" was held by the
      Hokkaido Medical Society at Hokkaido University Conference Hall on October 28,
      2000. Six speakers, including three medical doctors, a health nurse, a
      nutritionist and a physical therapist presented the most-update information on
      diabetes mellitus based on their specialty. The aim of this symposium was to
      consider how to support the self-management of patients with diabetes mellitus to
      keep a quality of life.

PMID- 11344903
TI  - [Behavioral and neurochemical study on the mechanism of the anxiolytic effect of
      a selective serotonin reuptake inhibitor, a selective serotonin1A agonist and
      lithium carbonate].
AB  - The authors investigated the effects of citalopram [selective serotonin (5-HT)
      reuptake inhibitor; SSRI] and MKC-242 (a selective 5-HT1A agonist) following
      treatment with subchronic lithium (p.o., 1 week) on the expression of conditioned
      freezing, an index of anxiety, and on extracellular 5-HT concentrations in the
      medial prefrontal cortex (mPFC). In conditioned fear stress experiments, acute
      administration of citalopram (s.c.) reduced freezing significantly at a high dose
      (30 mg/kg), while showing no effect at lower doses (3 and 10 mg/kg). Acute
      administration of MKC-242 (s.c.; 0.1-10 mg/kg) dose-dependently reduced freezing.
      Subchronic lithium treatment (1 week; 0.05 or 0.2% lithium carbonate in diet;
      p.o.) showed no effect on freezing behavior. Acute treatment with both citalopram
      (3 and 30 mg/kg) and MKC-242 (1 mg/kg) after subchronic treatment with high, but
      not low, concentrations of lithium (1 week) reduced freezing markedly and
      significantly, as compared with either drug alone. In brain microdialysis
      experiments, acute treatment with citalopram showed significant increases in the
      extracellular 5-HT concentrations in a dose-dependent manner. Subchronic lithium
      group showed significantly higher basal levels of extracellular 5-HT, compared
      with normal diet controls. Acute citalopram (3 and 30 mg/kg) treatment with
      subchronic lithium treatment showed significant increases in the extracellular 5
      HT concentrations, compared with citalopram treatment alone. Subchronic lithium
      did not cause decreases in extracellular 5-HT after presynaptic stimulation of 5
      HT1A receptors by MKC-242. These results suggest that subchronic lithium
      treatment enhanced the anxiolytic-like effects of these serotonergic drugs by
      facilitating central 5-HT neurotransmission at clinically therapeutic plasma
      lithium levels. It is hypothesized that subchronic lithium treatment gives an
      additive effect to the treatment with citalopram (3 and 30 mg/kg) by increasing
      the extracellular 5-HT concentrations in the mPFC, and that subchronic lithium
      treatment enhances the anxiolytic effect of MKC-242 by increasing sensitivity of
      postsynaptic 5-HT1A receptors.

PMID- 11344904
TI  - [Terminal complement complex (TCC) levels in urine in patients with renal
      diseases].
AB  - The terminal complement complex (TCC) has been reported to play an important role
      in the pathogenesis of proteinuria not only in experimental nephritis but also in
      human glomerulonephritis. In order to clarify the clinical significance of TCC,
      the author investigated a total of 129 pediatric patients with the following
      glomerular diseases: idiopathic nephrotic syndrome (INS; 40 cases), IgA
      nephropathy (IgAN; 48 cases), mesangio-capillary glomerulonephritis (MPGN; 16
      cases), lupus nephritis (LN; 16 cases), purpura nephritis (5 cases) and
      membranous nephritis (4 cases). Results were analyzed in relation to the
      responsiveness to steroid treatment in INS and the degree of proteinuria and
      histopathologic severity in glonerulonephritis groups. In 40 patients who
      underwent renal biopsy, the localizations of vitronectin and clusterin, both of
      which are regulatory proteins for TCC, were examined by immunofluorescence
      microscopy in conjunction with that of TCC for the study of the mechanism of
      local defense in glomerulonephritis. The urinary TCC levels were elevated in 9
      (90%) of 10 patients with steroid-resistant INS, while they were elevated only in
      2 of 30 steroid-responsive patients. In glomerulonephritis groups, urinary TCC
      levels were elevated in 13 of 48 patients with IgAN, 6 of 16 with MPGN, 8 of 16
      with LN, 2 of 5 purpural nephritis and 1 of 4 with membranous nephritis. Urinary
      TCC levels correlated with histological severity in IgAN and showed a reciprocal
      relation to C3 levels in MPGN and LN. Immunofluorescence findings showed that
      localization of TCC was quite similar to that of C3 in glomerulonephritis groups.
      Vitronectin and clusterin were also demonstrated to deposit in similar pattern to
      TCC. These results suggest that in INS urinary TCC levels could predict the
      responsiveness to steroid therapy and might be useful as a non-invasive
      diagnostic method in differential diagnosis of INS. In IgAN, urinary TCC could be
      a useful marker of histologic severity. The deposition of vitronectin and
      clusterin together with TCC in glomerulus suggests the possibility that
      vitronectin and clusterin play a role in reducing the formation of TCC in
      glomerular tissues.

PMID- 11344905
TI  - Glomerular expression of collagen IV alpha 1, alpha 3 and alpha 5 chains in
      childhood IgA nephropathy.

PMID- 11344906
TI  - [Downregulation of p57kip2 is involved in the proliferation of vascular smooth
      muscle cell (VSMC)].

PMID- 11344907
TI  - [Neural stem cells derived from adult human brain: implications for a cell
      therapy for CNS diseases].

PMID- 11344908
TI  - [Hemodynamic effects of STA-MCA anastomosis on patients with occlusion of the
      main cerebral artery].
AB  - PURPOSE: We studied cerebral circulation in patients with occlusion of the main
      cerebral artery and investigated the efficacy of STA-MCA anastomosis. PATIENTS
      AND METHODS: Thirty-six patients with occlusion of the main cerebral artery were
      studied. Twenty-three patients had occlusion of the internal carotid artery and
      13 had occlusion of the middle cerebral artery. The mean age was 62 years.
      Cerebral blood flow (CBF) was measured in all patients and cerebrovascular
      reactivity (CVR) was examined in 11 patients by xenon enhanced CT.
      Intraoperatively, cortical arterial pressure and anastomotic flow were measured.
      RESULTS: There was no perioperative mortality or morbidity. There was no
      ipsilateral stroke recurrence during the follow-up period averaging 35.1 months.
      Patency of the anastomosis was verified in 91% of the patients by magnetic
      resonance angiography. Twenty-three (64%) patients showed decreased CBF before
      the operation and 57% of these patients showed improvement to the normal range
      after STA-MCA anastomosis. All of the eight patients with decreased CVR showed
      improvement after the operation. Anastomotic flow correlated significantly with
      the cortical arterial pressure. CONCLUSION: STA-MCA anastomosis could improve
      cerebral circulation of patients with low CBF or low CVR due to occlusion of the
      main cerebral arterial. It was concluded that STA-MCA anastomosis may contribute
      to the reduction of stroke recurrence, if perioperative complications are
      reduced.

PMID- 11344909
TI  - [Long distance air transport by helicopter of a patient with severe head damage].
AB  - A report of a case of a patient with severe head trauma with pneumonia and
      cerebral infarction transported by helicopter. An eighty-year-old male was
      referred to our hospital because of dyspnea after a fall during sightseeing at
      Hiroshima. He was lucid at first, but, after two days presented restlessness due
      to brain contusional hemorrhage and edema. Moreover, he developed pneumonia and
      cerebral infarction during the period of his hospitalization. He was intubated
      and received central venous routing. While being transported, his consciousness
      showed moderate disturbance, aphasia and right hemiplegia. His family asked that
      therapy be continued near his house in Osaka. We selected transport by helicopter
      because of his bad general condition and because transport time would be much
      shorter. He was transported by helicopter to Osaka one month after admission.
      First, he was transported by ambulance to the airport of Hiroshima. He was
      carried to the helicopter at the airport. An oxygen cylinder was connected to the
      incubation tube via an ambu bag because direct connection between the oxygen
      cylinder and the intubation tube was impossible. Just before the take off, O2
      saturation was checked by the pulse oximeter of the ambulance. In the helicopter,
      there were six men; two pilots, two rescue men, one doctor and the patient.
      Suction was applied only once and there was no trouble during the flight. The
      weather was fine and the helicopter experienced almost no rolling during the
      flight. The flight time was only one hour and twenty minutes. The helicopter
      safely landed at an emergency heliport in Osaka. The patient was carried to a
      waiting ambulance and transported to the hospital. Total transport time was only
      two hours and thirty minutes. This is a case showing a helicopter could safely
      transport a patient with severe brain damage over a long distance in a short
      time.

PMID- 11344910
TI  - [Spontaneous resolution of cervical syringomyelia. A case report].
AB  - A 54-year-old man visited our hospital with complaints of severe pain in the neck
      and the right upper limb. His MR (magnetic resonance) imaging showed a cervical
      syringomyelia associated with Chiari I malformation. After one month, his
      complaints vanished smoothly, and the repeated MR imaging revealed shrinkage of
      the syrinx. The mechanisms of spontaneous resolution of syringomyelia were
      discussed according to some relevant literature.

PMID- 11344911
TI  - [A case report of aspergillus granuloma in the cavernous sinus].
AB  - We encountered a case of aspergillus granuloma in the cavernous sinus originating
      in the left sphenoid sinus. The patient was a 56-year-old woman who complained of
      visual loss and cavernous sinus syndrome on the left side. Hematological data
      were within normal limits. Bone CT showed evidence of bone destruction in the
      roof of the left sphenoid sinus. MR images with gadolinium demonstrated an
      enhanced heterogeneous mass extending from the left sphenoid sinus to the
      cavernous sinus and the orbital apex. Angiography showed occlusion of the left
      internal carotid artery. Dexamethasone was administered intravenously every day,
      because the patient was diagnosed as having Tolosa-Hunt syndrome (THS). However,
      dexamethasone was not effective. We carried out a biopsy of the mass from the
      sphenoid sinus, and findings showed aspergillosis. On the 19th day after
      initiation of fluconazole treatment, the patient lapsed into unconsciousness and
      presented left hemiparesis. T2-weighted MR images showed high intensity areas in
      the pons and the thalamus. The patient died two days later. An autopsy revealed
      edema and many infarctions throughout the brain. The cavernous sinus had been
      replaced completely with aspergillus granuloma. Furthermore, numerous hyphae of
      aspergillus had adhered to the inside of the basilar artery, and caused
      occlusions of arteries around the brain. This case indicated the difficulty of
      diagnosis of THS and the hazard of over-application of steroids. In this paper,
      we describe the clinical and pathological behavior of aspergillosis in the
      cavernous sinus.

PMID- 11344912
TI  - [Hemangioblastoma of the spinal nerve root].
AB  - A case of extramedullary spinal root hemangioblastoma is described. A 44-year-old
      male presented with gait disturbance. Magnetic resonance (MR) imaging revealed a
      round enhanced mass at the level of T8. Spinal angiography showed a vascular
      tumor fed by the posterior spinal artery via the left T9 intercostal artery. A
      laminectomy of T8-T9 was performed, and a reddish brown-colored soft tumor
      originating in the T9 posterior spinal nerve root was exposed. The postoperative
      course was uneventful. This is the first reported case of a spinal root
      hemangioblastoma that was not related with Von Hippel-Lindau disease.

PMID- 11344913
TI  - [Spontaneous dissection of the anterior cerebral artery presenting subarachnoid
      hemorrhage and cerebral infarction: a case report].
AB  - A case is reported of anterior cerebral artery dissecting aneurysm presenting
      with subarachnoid hemorrhage and cerebral infarction. A 50-year-old man presented
      with sudden onset of weakness of the left lower limb was admitted to our
      hospital. CT scan on admission showed a subarachnoid hemorrhage in the
      interhemispheric fissure and CT on the 6th day demonstrated a cerebral infarction
      on the right medial frontal lobe. A carotid angiogram 12 hours after the onset
      showed no aneurysmal lesion, but, the angiogram repeated 11 days after the onset
      revealed an aneurysmal dilatation with distal narrowing at the right A2-A3
      segment. To prevent rebleeding, we performed a wrapping procedure through the
      interhemispheric route on the 18th day after onset. The postoperative course was
      uneventful. We reviewed 27 previously reported cases with symptomatic dissecting
      aneurysm confined to the anterior cerebral artery.

PMID- 11344914
TI  - [A case of cervical subpial lipoma].
AB  - The authors report the rare case of a 48-year-old woman with a cervical subpial
      lipoma unassociated with spinal dysraphism. Her symptoms were progressive
      weakness and numbness in the four extremities and the neurological symptom of
      mild cervical myelopathy. Plain radiographs of the cervical spine showed diffuse
      widening of the spinal canal, which was occupied by a large low-density mass
      revealed by axial CT scan. MR imaging identified the mass as being dorsolateral
      to the cord in the intradural region. It was hyperintense on both T1- and T2
      weighted images. Axial images with fat suppression sequence clearly showed dorsal
      nerve roots traveling through the lesions, but the interface between the spinal
      cord and lesion was not well demarcated. A cervical laminectomy between C3-6
      revealed a yellowish subpial mass after the dura was opened. The mass was only
      partially resected and intraoperative SEP monitoring data remained normal
      including N20 latency. Histological examination found mature adipose tissue
      covered by thickened pia mater, which was compatible with a diagnosis of lipoma.
      After surgery, no complications occurred and the patient's myelopathy
      subsequently improved. Subpial spinal lipomas unassociated with dysraphism are
      uncommon and they are reported in only 1% of all spinal cord tumors. They are
      thought to arise from premature dysjunction of the cutaneous ectoderm during
      neural tube formation. Without any invasive procedure, MR imaging is
      indispensable to show their longitudinal dimension as well as their infiltrative
      extension into the spinal cord. The main purpose of surgery is to decompress the
      lipoma from the adjacent neural structures, because it is benign in nature and
      there is no cleavage plane identifiable between the lipoma and the spinal cord.

PMID- 11344915
TI  - [Dissecting aneurysm of the middle cerebral artery (M1-2 portion) with
      subarachnoid hemorrhage: a case report].
AB  - We report a SAH case of a ruptured dissecting aneurysm of the middle cerebral
      artery following parietooccipital subcortical hemorrhage. A 68-year-old woman was
      admitted to our hospital, complaining of headache. On admission she was alert
      with left homonymous hemianopsia. A CT scan disclosed subcortical hemorrhage in
      the right parieto-occipital lobe. An angiogram revealed no abnormal vessels.
      Seven days after admission, she suddenly lapsed into unconsciousness with left
      hemiparesis. A CT scan demonstrated subarachnoid hemorrhage with a right sylvian
      hematoma. A second angiogram revealed fusiform dilatation of the M2 branches and
      aneurysmal dilatation at the M1-M2 bifurcation. Following conservative therapy,
      she died 21 days after admission. The relationship between subcortical hemorrhage
      and the subsequent subarachnoid hemorrhage was not certain. We discuss and review
      the treatment of a dissecting aneurysm of the middle cerebral artery.

PMID- 11344916
TI  - [A case of cerebral arteriovenous malformation complicated with intracerebral
      hemorrhage after endovascular embolization].
AB  - We reported a case of cerebral arteriovenous malformation (AVM), complicated with
      intracerebral hemorrhage (ICH), after endovascular embolization. A 51-year-old
      male suffered from intraventricular hemorrhage due to a rupture of an intranidal
      aneurysm on October 4, 1999. The first embolization procedure for the aneurysm
      and a part of the nidus was performed with 2-hydroxyethyl methacrylate-methyl
      methacrylate (HEMA-MMA) and Liquid coil on day 21 after admission. On day 28, a
      second embolization was carried out for the residual nidus. Although most of the
      nidus was obliterated, the patient became comatose 10 hours after the second
      embolization. Computed tomography revealed a massive ICH in the right parietal
      lobe, and he underwent emergency evacuation of the hematoma. During the surgery,
      HEMA-MMA was seen in a draining vein. This caused venous stasis. Although the
      patient gradually improved postoperatively, he became comatose again because of a
      recurrence of ICH on day 36. Evacuation of the hematoma and removal of the nidus
      were performed again. The operative specimen showed AVM embolized by HEMA-MMA
      with non-specific inflammation and partial inflammatory degeneration of the
      vascular wall. Hemodynamic change such as venous stasis or elevated pressure of
      the feeding artery seemed to be the cause of the hemorrhage. Multi-staged
      embolization with longer intervals and intraoperative flow control were regarded
      as crucial for avoiding delayed hemorrhage.

PMID- 11344918
TI  - [Health insurance and insurance for care and assistance for the elderly in
      Japanese neurosurgical consultation].

PMID- 11344917
TI  - [A case of familial cerebral cavernous angioma and review of Japanese cases].
AB  - We present one pedigree of familial cerebral cavernous angioma (FCCA). Case 1 was
      a 52-year-old male with right hemiplegia. When he was 37 years old, a left
      occipital lesion was excised and histologically diagnosed as cavernous angioma.
      MR image showed many cavernous angiomas in the right temporal lobe, the right
      paraventriclar white matter, the right frontal lobe, the left basal ganglia, and
      the left parietal lobe. Stereotactic radiosurgery was undertaken for all the
      lesions. Although the size of each lesion was unchanged, neither hemorrhage nor
      neurological deterioration were recognized after radiosurgery. Case 2 was a 24
      year-old male, a son of the patient in case 1. He has manifested tonic-clonic
      type epilepsy since the age of 2. MR image showed cavernous angiomas in the pons,
      the right frontal, and the left intra-Sylvian regions, and many paraventricular
      cysts with rims indication of previous hemorrhages. Two de novo lesions were
      observed on subsequent annual MR screening. Surgical excision for the left intra
      Sylvian lesion and stereotactic radiosurgery for all lesions were undertaken.
      Histological diagnosis was cavernous angioma. In the literature, there were 17
      pedigrees and 37 cases of FCCA in Japan. The incidence of both multiple lesions
      and hemorrhage were less than in found in Spanish or French cases. Stereotactic
      radiosurgery is considered an useful treatment for FCCA, because lesions are
      multiple and de novo lesions occur.

PMID- 11344919
TI  - Medicine and spirituality.

PMID- 11344920
TI  - MedBytes.

PMID- 11344921
TI  - Turning the tables. Bill would give physicians recourse against frivolous
      lawsuits.

PMID- 11344922
TI  - Technological healing.

PMID- 11344923
TI  - Less money, more demand. Soaring Medicaid costs putting lawmakers in budget
      crunch.

PMID- 11344924
TI  - Truth in advertising. Physicians question insurers' marketing tactics.

PMID- 11344925
TI  - Teaching to heal. Part 2: Asking the right questions.

PMID- 11344926
TI  - Evaluating rabies exposure.

PMID- 11344927
TI  - Any screening beneficial.

PMID- 11344928
TI  - Try hypnotherapy and acupuncture.

PMID- 11344929
TI  - Prenatal treatment of congenital adrenal hyperplasia. The United States
      experience.
AB  - Based on the author's experience, prenatal diagnosis and treatment of 21
      hydroxylase deficiency is safe and effective in significantly reducing or
      eliminating virilization in the affected female, and the same outcome seems to be
      true in the treatment of 11 beta-hydroxylase deficiency. Prenatal treatment
      spares the newborn female the consequences of genital ambiguity, genital surgery,
      sex misassignment, and gender confusion. Of the monogenic disorders, steroid 21-
      and 11 beta-hydroxylase deficiency are two of the few in which prenatal treatment
      is effective and influences postnatal life.

PMID- 11344930
TI  - The genetics, pathophysiology, and management of human deficiencies of P450c17.
AB  - P450c17 commands a central role in human steroidogenesis as the qualitative
      regulator of steroid hormone flux. Consequently, the study of P450c17
      deficiencies in human beings serves to illustrate many aspects of the physiology
      of steroid biosynthesis and to demonstrate salient features of the genetics and
      biochemistry of P450c17 itself. Furthermore, classic 17-hydroxylase deficiency
      was first described in patients with sexual infantilism and hypertension, but it
      is now recognized that partial and selective forms of P450c17 deficiencies also
      exist. These patients demonstrate a range of phenotypes, illustrating the
      multiple roles of P450c17 in human biology. This article reviews the genetics and
      biochemistry of P450c17 as a prelude for understanding the pathophysiology of
      these diseases and approaches to their diagnosis and management.

PMID- 11344931
TI  - New ideas for medical treatment of congenital adrenal hyperplasia.
AB  - During the past 50 years since the discovery of cortisone therapy as an effective
      treatment for CAH, many advances have been made in the management of 21
      hydroxylase deficiency. Despite these advances, the clinical management of
      patients with CAH is often complicated by abnormal growth and development,
      iatrogenic Cushing's syndrome, inadequately treated hyperandrogenism, and
      infertility. New treatment approaches to classic CAH represent potential
      solutions to these unresolved issues. At the National Institutes of Health, a
      long-term randomized clinical trial is investigating a new treatment regimen: a
      reduced hydrocortisone dose, an antiandrogen, and an aromatase inhibitor.
      Peripheral blockade of androgens may also be helpful in the adult woman with CAH
      and PCOS. Other promising new treatment approaches include LHRH agonist-induced
      pubertal delay with or without growth hormone therapy, alternative glucocorticoid
      preparations or dose schedules, CRH antagonist treatment, and gene therapy. The
      applicability and success of these new approaches await the results of current
      research.

PMID- 11344932
TI  - Surgical treatment of congenital adrenal hyperplasia.
AB  - Unraveling of the genetics of CAH offers the possibility of earlier detection and
      prenatal treatment or, alternatively, blastocyst embryo selection and eventually
      in utero gene therapy. Endocrine, surgical, and anesthesia management after birth
      have improved, leading to a better outcome for these patients. In the authors'
      experience, early one-stage reconstructive surgery, although demanding, allows
      one to use all available tissue. Once mastered, the repair is actually
      technically easier than vaginal pull-through surgery in the adolescent. Patients
      go through childhood with a body image that is more concordant with normal.
      Neither the child nor the parents must suffer the anticipation of a major
      operative intervention at puberty that can cause great emotional stress and that
      may be more difficult. The authors have encountered situations in late
      adolescence in which it has been impossible to separate the urogenital sinus from
      below. Under these circumstances, one can consider a posterior sagittal approach
      in which the rectum is bivalved to allow one to approach the vagina from below in
      an attempt to separate it safely from the urethra and to mobilize it to the
      perineum. It is also feasible to consider fashioning a segment of sigmoid colon
      as a neovagina, realizing that mucosal drainage needs to be managed daily. The
      authors have also encountered the rare 46,XX patient raised as a male and
      committed to the male role. In these cases, the patient can be offered
      gonadectomy, followed by staged complex hypospadias repair, and surgery to remove
      Mullerian structures and, if possible, to preserve the vas, followed by prepenile
      scrotal repair and insertion of testicular prostheses. Children with CAH require
      a lifetime of care with surgical approaches that are age appropriate. These
      patients can lead a full and productive life. It is the physician's
      responsibility to make certain that these children reach their full potential
      with the least number of interventions, which should be designed and optimized to
      produce the best possible outcome.

PMID- 11344933
TI  - Newborn screening for congenital adrenal hyperplasia.
AB  - Classic CAH (salt-wasting and simple virilizing) meets all of the recommended
      criteria for newborn screening. There are reliable and efficient newborn
      screening tests, the disorder results in high morbidity and mortality if left
      undetected, there is effective treatment that reduces negative outcomes, and
      there is a relatively high incidence. When compared with the case findings
      without the benefit of screening, the data from screening programs show reduced
      adrenal crises, reduced incorrect sex assignments, and reduced deaths.
      Racial/ethnic prevalence differences are present in newborn screening program
      data.  The Texas data indicate a lower disease frequency in African-Americans
      when compared with Caucasians, and international data indicate higher frequencies
      in native Yupik Eskimos, Brazilians, residents of La Reunion, and Filipinos. When
      worldwide clinical ascertainment data are compared with newborn screenng data, it
      is clear that newborns with CAH (especially males) die when screening is not
      done.  To be effective in reducing mortality, newborn screening must be performed
      soon after birth, and the results must be available quickly so that early salt
      wasting crises can be averted.  It is preferable that newborn screening
      laboratiories be operational 7 days a week, and that sample delivery from the
      collection site to testing laboratory be as efficient as possible, including
      weekends and holidays, so that undue testing delays are not encountered.  These
      two requirements pose major challenges for most programs, but they are critical
      to optimal screening outcome.  Based on the studies in Texas, with second
      screening samples collected at approximately 2 weeks of age, some newborns with
      simple virilizing CAH are missed on initial screening using current testing
      protocols.  There is need to set a screening cut-off such that the false-positive
      rate does not oversaturate the follow-up system, in part owing to the
      insensitivity of current kit methodologies and the biochemical manifestations of
      CAH.  With advances in genetic testing procedures and improved automation
      techniques, it may soon be possible for CAH screening programs to include
      genotyping as a second-tier  confirmation as a part of the newborn screening
      protocol.  Despite the fact that CAH is a continuum of disorders, the correlation
      between genotype and phenotype is fairly consistent in most cases.  For the
      purpose of screening, genotyping  will likely be useful only for differential
      diagnoses of non-salt wasters, given the necessary time constraints and expense
      of obtaining genotypes and the need for immediate diagnosis/treatment of salt
      wasters.  It is hoped that newborn screening programs will begin to provide
      answers to some  of these question in addition to their primary function of
      reducing the morbidity and mortality resulting from CAH.

PMID- 11344934
TI  - Gender and sexuality in classic congenital adrenal hyperplasia.
AB  - The current debate about the psychosocial management of intersex patients has
      significant implications for 46,XX patients with classic congenital adrenal
      hyperplasia (CAH) in two respects: (1) the question of genital surgery for
      reasons other than purely medical ones before the patient is old enough to give
      informed consent, and (2) the question of gender assignment in severely
      masculinized patients. This article reviews the status of the empirical evidence
      for the development of gender and sexuality in 46,XX persons with classic CAH and
      its implications for clinical practice.

PMID- 11344935
TI  - Cognitive function in congenital adrenal hyperplasia.
AB  - Cognition in patients with CAH has not been as well studied as other aspects of
      psychologic function. Nevertheless, it is possible to make some conclusions and
      to offer a number of hypotheses for further study (Table 1). First, patients with
      CAH do not seem to have an overall intellectual advantage as a direct consequence
      of the disease. The high IQs reported in some groups of patients with CAH are
      also reported in their siblings and probably reflect sampling bias. Second, it is
      possible that, on average, patients with salt-wasting CAH have lower overall
      ability than patients with the simple-virilizing form, but both groups are well
      within the normal range, and there is considerable variability among both groups.
      Third, the evidence to date does not confirm that patients with CAH are more
      likely to have diagnosable learning disabilities when compared with their
      unaffected relatives, but this issue has not been well studied with the
      appropriate psychoeducational assessments. It is unlikely that patients with CAH
      are at substantially increased risk for frank learning disabilities, but they may
      be likely to have problems in specific areas. Fourth, females with CAH seem to
      have enhanced spatial ability as a result of exposure to high levels of androgens
      early in development. The neural substrate of this advantage is unknown but a
      subject of active research. It is unclear whether when compared with their
      unaffected siblings, females with CAH are better in other abilities that are
      typically performed best by males or worse in abilities typically performed best
      by females. Fifth, it is likely that patients with CAH have other cognitive
      changes as a consequence of disease characteristics (besides androgens) and of
      the treatment of the disease. Some evidence suggests that patients with CAH are
      more likely to have white-matter brain changes produced by the disease and its
      treatment. This has not been well studied but should be because of the potential
      clinical implications. It is reasonable to hypothesize that there will be
      cognitive changes that reflect effects of undertreatment (e.g., ACTH effects on
      attention) and other changes that reflect effects of overtreatment (e.g.,
      glucocorticoid effects on memory). Some of these effects may be transient,
      reflecting acute brain changes, whereas others may become chronic as a result of
      permanent brain changes with repeated exposure. There is need for continuing
      study of cognition in patients with CAH. Such studies will provide basic
      information about hormonal effects on cognition and the neural mechanisms that
      mediate those effects. They will also provide important clinical information to
      guide psychologic and medical treatment of patients.

PMID- 11344936
TI  - Congenital adrenal hyperplasia owing to 21-hydroxylase deficiency. Growth,
      development, and therapeutic considerations.
AB  - In the absence of long-term results of experimental therapies, a common sense
      approach toward dealing with the growth of patients who have CAH is desirable.
      First, an effort can be made to decrease the replacement cortisol dose during the
      first year of life. Doubling, rather than tripling, the basal dose at times of
      stress could be helpful. The use of adjunctive therapy for infections could
      result in fewer fevers. After 1 year of age, mean parental height could be used
      to establish at which centile the child should theoretically grow. The dose of
      cortisol could be adjusted to maintain the bone age between +/- 1 SD. Plasma
      androstenedione levels should not rise above 50 ng/dL, and 17-hydroxyprogesterone
      should not be totally suppressed but be maintained between 500 and 1000 ng/dL.
      Compliance with therapy should be encouraged, particularly for adolescent
      patients. In the final analysis, a realistic expectation for patients would be a
      height between the 50th and third percentile of the normal growth curve and, in
      some cases, slightly below the third percentile when the genetic potential is
      slight.

PMID- 11344937
TI  - Pregnancy outcomes in women with congenital virilizing adrenal hyperplasia.
AB  - Although low fertility rates have traditionally been reported among women with
      classic CAH and especially among women with the salt-wasting variant, more recent
      data suggest that fertility rates are significantly improved, largely owing to
      earlier treatment of CAH, improved compliance with therapy, and surgical advances
      in genital reconstruction. Furthermore, ovulation induction and assisted
      reproductive techniques are now available to women who remain infertile despite
      effective adrenal androgen suppression. Although the pregnancy experience in
      women with classic CAH remains limited, it is apparent that, once pregnant, these
      women have a high probability of successful outcome. Key issues should be
      emphasized in the management of CAH during gestation, including the need for
      assessing adrenal steroid replacement and adrenal androgen suppression,
      particularly in light of the interplay between maternal hyperandrogenism and the
      protective effect of placental aromatase activity, which provides a relatively
      large margin of safety for the female fetus. Maternal hormone levels should be
      evaluated in the context of laboratory-specific reference ranges for pregnancy.
      The infant should be examined for ambiguous genitalia and monitored for evidence
      of adrenal insufficiency. Although an affected female infant with classic CAH has
      not been reported as a pregnancy outcome of a mother with classic virilizing CAH,
      these concerns should be discussed during preconception counseling. Patients
      should also be aware of the importance of medication compliance and careful
      hormonal monitoring during the entire pregnancy. In most cases, successful
      gestational management requires the close coordination of care between the
      obstetrician and endocrinologist.

PMID- 11344938
TI  - Congenital adrenal hyperplasia owing to 21-hydroxylase deficiency.
AB  - Congenital adrenal hyperplasia (CAH) owing to 21-hydroxylase deficiency is the
      most common cause of genital ambiguity in the newborn and is present in about 1
      in 15,000 live births worldwide. The disease is further characterized in its
      classic salt-wasting form (approximately 75% of cases) by potentially lethal
      adrenal insufficiency. A non-salt-wasting form of classic CAH with 21-hydroxylase
      deficiency is also recognized by genital ambiguity in affected females and by
      signs of androgen excess in later childhood in males. Nonclassic CAH with 21
      hydroxylase deficiency may be detected in 1% to 3% of populations and is often
      mistaken for idiopathic precocious pubarche in children or polycystic ovary
      syndrome in young women. This article presents an overview of clinical and
      genetic aspects of the various forms of CAH with 21-hydroxylase deficiency.

PMID- 11344939
TI  - Steroid 11 beta-hydroxylase deficiency and related disorders.
AB  - Three disorders result from mutations involving two closely linked 11 beta
      hydroxylase genes. Steroid 11 beta-hydroxylase deficiency results from mutations
      in CYP11B1. This is a form of congenital adrenal hyperplasia (CAH) characterized
      by hypertension and signs of androgen excess. Mutations in CYP11B2 cause
      aldosterone synthase deficiency, an isolated defect of aldosterone biosynthesis.
      Recombinations between these two genes cause glucocorticoid suppressible
      hyperaldosteronism, an autosomal dominant form of hypertension.

PMID- 11344940
TI  - Congenital adrenal hyperplasia owing to 3 beta-hydroxysteroid dehydrogenase
      deficiency.
AB  - Recent advances in the genetics of the family of 3 beta-hydroxysteroid
      dehydrogenase (3 beta-HSD) enzymes have helped in the understanding of the
      molecular basis and hormonal phenotype of bona fide 3 beta-HSD deficiency
      congenital adrenal hyperplasia (CAH). This article revisits the clinical spectra
      of 3 beta-HSD deficiency disorders, pathophysiology of 3 beta-HSD deficiency CAH,
      and updates genotype findings and diagnostic hormonal criteria for bona fide
      classic and nonclassic 3 beta-HSD deficiency CAH. The delta-5 steroid abnormality
      for the nonclassic 3 beta-HSD deficiency CAH, proven by genotype study, is
      substantially greater than the hormonal criteria for the disorder published
      before the advent of molecular information on the gene encoding adrenals and
      gonads in humans. In hyperandrogenic children and women, the pathogenic mechanism
      of a subtle abnormality in adrenal 3 beta-HSD activity, determined by modestly
      elevated ACTH stimulated delta-5 steroid levels, which led to the diagnosis of
      mild nonclassic 3 beta-HSD deficiency in the past, is outside of the type II 3
      beta-HSD gene which encodes adrenals and gonads in humans and remains to be
      further explored.

PMID- 11344943
TI  - [Alterations of the integument of fattening pigs in different housing systems].
AB  - Alterations of the integument of fattening pigs were investigated on a total of
      eleven farms with the following housing systems: "Krieger" system, fully slatted
      floors, partially slatted floors and kennel housing systems. For this purpose,
      the alterations of the integument of the animals were visually assessed at
      different times during fattening. In addition, spot investigations were carried
      out on three farms with deep litter systems. In the non-littered systems,
      significantly more changes at the limbs were observed than in the littered
      systems. The least damages occurred in the deep litter system. Similar as with
      cattle, soft and deformable lying areas seem to be a prerequisite for the
      prevention of such alterations. With respect to injuries caused by tailbiting,
      apart from possibilities of activity, other parameters such as air quality and
      space availability also play an important role.

PMID- 11344942
TI  - [Malignant catarrhal fever in Switzerland. 1.Epidemiology].
AB  - Malignant catarrhal fever (MCF) is a usually fatal infectious disease of cattle
      with global distribution. Based on the recent introduction of a diagnostic PCR
      assay and a competitive inhibition ELISA (ciELISA) epidemiological data were
      collected on field cases in Switzerland. Throughout a three-year period, an MCF
      incidence of 0.6@1000 was observed, with a gradient of cases from Eastern to
      Western Switzerland. While the cantons Wallis, Vaud and Geneva reported no and
      the remaining western cantons only reported a few cases, the highest incidence
      was observed in the cantons Appenzell Innerrhoden, Lucern, Glarus, Grison, St.
      Gallen, Schwyz, and Thurgau. MCF occurred seasonally and an age-related
      clustering was also observed. About 50% of all cases and all outbreaks with more
      than one animal in a single herd occurred between April and June. Animals between
      six months and two years were strongly over represented. Observations on four
      surviving cattle showed that the outcome of the disease is not invariably fatal
      and that these persistently infected cows can produce healthy negative calves.
      Investigations on the aetiology indicate that the main reservoir for OvHV-2 is in
      sheep and possibly goats, while cattle do not normally harbor the virus. An OvHV
      2 negative sheep herd was raised from lambs, which were reared colostrum-free and
      in isolation from their mothers. The success rate clearly indicated that vertical
      intrauterine infection is not the main mode of transmission among sheep.
      Therefore, horizontal, seasonally occurring transmission of OvHV-2 among sheep
      has to be assumed.

PMID- 11344944
TI  - [Causes of death, zoonoses, and reproduction in the European brown hare in
      Switzerland].
AB  - To elucidate the importance of different causes of mortality which could explain
      the downward trend of the hare populations in Switzerland and for monitoring
      selected zoonoses, the health and reproductive status of 167 perished brown hares
      (Lepus europaeus) was assessed. Concerning causes of mortality, traumas were by
      far the most frequent diagnosis, 80% of the hares dying because of injuries.
      Animals killed by road traffic were highly represented. Predators (such as dogs,
      domestic cats, lynx, martens, buzzards, and golden eagles) killed 16% of the
      analysed animals. In juveniles, predation was significantly more frequent than in
      adults. Infectious diseases led to death in 15% of the animals, and cases of
      pasteurellosis, brucellosis, pseudotuberculosis, tularaemia, listeriosis, and
      toxoplasmosis were diagnosed. In 5% of the hares, the cause of death pertained to
      other categories or remained unclear. Reproductive performance was judged to be
      normal, since mean litter size was 2.5 per female and pregnancy rate in March
      June was 74%. We conclude that neither a specific infectious disease, for which
      adult hares are particularly susceptible, nor an insufficient reproductive
      performance are responsible for the decline of brown hare populations in
      Switzerland. This phenomenon is rather a cause of a reduced survival rate in
      leverets.

PMID- 11344945
TI  - [Polycystic kidney disease in a Persian cat].
AB  - This case report is about a 9-year-old male castrated Persian cat with chronic
      renal failure. After physical examination and ultrasonography polycystic kidney
      disease (PKD) was diagnosed. Various aspects of etiology, pathophysiology and
      diagnosis of PKD are discussed.

PMID- 11344946
TI  - [Wellness--fitness--doping].

PMID- 11344947
TI  - [Wellness holidays--wholesome wish or one-sided reality].
AB  - The term wellness is widely used in European tourism. The principal observations
      regarding the wellness industry concern an expanding supply of and an
      insufficiently researched demand for wellness programs. The quality dimension of
      wellness services is increasingly becoming the decisive competitive factor. For
      this reason quality management plays an important role. Market research shows
      that average 3- to 5-star hotels provide fairly comprehensive wellness
      facilities. Wellness hotels should therefore specialize in health information,
      individual care and a wide range of cultural and relaxation programs. Although
      the same hotel can host cure and wellness guests at the same time, these two
      segments have to be considered separately when deciding on the marketing
      strategy. We therefore assume that wellness is pursued solely by 'healthy'
      people, the prime aim being prevention. 'Normal cure guests' aim to heal their
      illness.

PMID- 11344948
TI  - [Athletic training or daily movement activities for optimal health and quality of
      life].
AB  - During the 70ies and 80ies, it was mainly endurance training that was recommended
      for disease prevention and health promotion. During the 90ies, the health
      enhancing value of moderate-intensity exercise, including daily lifestyle
      activities, has been recognized. Considering two lines of evidence-
      epidemiological findings from observational studies and 'physiological' results
      from experimental training studies to alter specific disease risk factors--it
      becomes clear that physical activity and exercise of different intensities and
      durations will produce different biological outcomes. Therefore, both vigorous
      exercise and moderate-intensity lifestyle activities have their specific
      advantages and disadvantages which may help to optimize individual choices for
      physical activity. Two years ago, the Swiss Federal Office of Sports and the
      Swiss Federal Office of Public Health have published their joint recommendation
      for health-enhancing physical activity; these guidelines try to combine the
      advantages of daily activities of moderate intensity, cardiorespiratory fitness
      training and strength/flexibility exercises as well as further sports activities.

PMID- 11344949
TI  - [Promotion of exercise among the physically inactive: a challenge also in
      Switzerland].
AB  - The scientific evidence for the importance of regular physical activity for
      health is beyond any doubt. This association is widely known and physical
      activity promotion activities are generally appreciated by the general
      population. Nevertheless the prevalence of physical inactivity in Switzerland is
      still rising. A growing number of large scale physical activity promotion
      projects like << Allez Hop! >>, Vita Parcours and the 'Feel Your Power' campaign
      of the Swiss Foundation for Health Promotion have begun to target physically
      inactive individuals. Intervention studies have given first indications of both
      the possibilities and the limitations of behavioural change. The 'Office in
      Motion' study used the ecological or settings approach in a white collar worksite
      intervention and has shown encouraging changes in previously inactive
      individuals. A number of ongoing studies based on the transtheoretical model in
      the primary care setting ('Active upon Advice'), in a military context
      ('Fitcheckplus') and on the Internet ('Active online') have shown positive
      preliminary results. A tourist region pilot study ('Heidiland aktiv') is used to
      illustrate the potential limitations of intervention projects: though a promising
      counselling system was developed and put in place it was not possible to develop
      an effective approach to the tourists and to generate sufficient interest in the
      issue to justify a full scale outcome study. These experiences from Switzerland
      show that behavioural change in previously inactive individuals is possible and
      that the general practitioner in particular can play an important role in this
      process. Expectations concerning the size of the intervention effect have to be
      realistic. Promotion of health enhancing physical activity remains a challenge.

PMID- 11344950
TI  - [Play sports and feel well! Effects of sports on mental health].
AB  - The role of mental health is increasingly recognised in the discussion about
      health. In this article, health is considered to be a dynamic balance between
      resources and potential risk factors. Sport and physical activity may represent
      resources that do not only contribute to an increased well-being, but also to an
      improved self concept as a cognitive representation of one's health-status.
      Investigations of the short-time effects of sport show that different activities
      result in different mood changes, but also that the initial mood is important in
      such a way that people with a bad mood profit more from physical activity
      programmes. More permanent physical activity results in better well-being, but
      also in an improved perception of the health status and a higher satisfaction
      with health. Individually tailored new physical activity behaviour programmes and
      reinforcing systems have to be developed. These may lead to adequately strengthen
      the self-efficacy and increase the well-being of a broader population.

PMID- 11344951
TI  - [Endurance training for fitness--role of individualized training program].
AB  - There are many different aspects that should be taken into account when exercise
      counselling of trained and untrained persons is required. Factors to be
      considered include the endurance capacity (EC), the general sport skills and the
      goals of the individual willing to start a training program. First the advisor
      should try to characterize the EC of the person by estimating or measuring EC.
      Based on this information, advice for an individual training programme can be
      given. As a principle for cardio-respiratory fitness training, a person should at
      least practise three times per week 20-30 minutes in a moderate exercise
      intensity to achieve a sufficient training effect. When training more than three
      times/week people should vary the mode of exercise and training intensity to
      improve the quality of training and to avoid overcharge symptoms. After a certain
      duration of the training cycle, the plans should be adapted to new or changed
      conditions. A distinct improvement of EC can be expected after 8-12 weeks of
      regular training. The article gives an overview of the possibilities for testing
      and the planning of training, should help the reader either to start his own
      training program or to give appropriate advice to an athlete requiring training
      counselling.

PMID- 11344952
TI  - [How much strength is needed for fitness?].
AB  - In order to tolerate the exertion in fitness exercise in the long term a
      sufficiently strong trunk musculature should be aimed at. In order to stabilize
      and balance the trunk and the pelvis there should be an optimal interaction of
      the muscles of the abdomen, the lateral trunk, the back and the flexors and
      extensors of the hip. If that balance is disrupted, muscular imbalance and a
      weakening or shortening of the muscles involved can occur. That imbalance leads
      to inadequate and excessive strain of the functional system of spine and pelvis.
      The functional anatomy of the trunk is described with clinical references in
      order to elucidate this context. A program of strength and stretching exercises
      for the trunk is presented suited to the needs of those practicing fitness
      exercise.

PMID- 11344953
TI  - [Fight against doping--national and international developments after Tour de
      France 1998].
AB  - After the scandal at the Tour de France 1998, the fight against doping was
      intensified on national as well as international levels. In particular, the
      foundation of the new World Anti-Doping Agency (WADA) has been a landmark: for
      the first time in the history of the fight against doping, there exists now an
      international structure that includes partners from the Olympic movement as well
      as from the governments. The importance of the WADA has already been demonstrated
      during the Olympic Games 2000 in Sydney. First, it conducted several thousands of
      un-announced doping tests internationally and second, members of the WADA acted
      as independent observers to judge the carrying out of doping controls during the
      games. In Switzerland, important new measures were taken in the past years: The
      introduction of an independent attorney for the judgment of sanctions or the
      employment of four professional doping control officers had a clear effect on the
      quality of doping controls. In addition, research--e.g. a survey on the
      perception of doping among the population or the development of new technologies
      for doping analysis--was intensified. In the fields of information and
      prevention, the existing printed material was extended with a website on doping
      (www.dopinginfo.ch). Furthermore, international cooperation to develop new
      didactical material for schools is intended. On the legal level, Switzerland will
      introduce a new law in mid 2001. It will enable the government to fight against
      the entourage of athletes when it provides doping substances to athletes. The
      sanctioning of athletes using doping will still be in the jurisdiction of the
      sports federations.

PMID- 11344955
TI  - [Doping-related problems in clinical practice].
AB  - The complexity of the new antidoping regulations of the International Olympic
      Committee (IOC), the International Federations (IF) and the National Olympic
      Committees (NOC) rises a lot of problems in handling the prescriptions of
      medication in athletes in the daily practice. In addition, several countries have
      passed antidoping laws which makes the prescription and the delivery of doping
      agens illegal. This may have severe consequences for the prescribing doctors. It
      is therefore the goal of the article to inform the practitioning doctors about
      the new antidoping regulations and their impact on prescribing or delivering
      potential doping agens to athletes. It will focus on the new dopinglists, the
      different doping control systems, the problems with the pharmacological treatment
      of certain diseases as asthma and the necessary reports which have to be sent to
      the NOC's or the IF's after prescribing certain medications or methods.

PMID- 11344954
TI  - [Misuse of drugs in recreational sports].
AB  - The extent of drug abuse in mass sport is only poorly documented. Studies about
      drug abuse investigated only the prohibited substances according to the Olympic
      movement antidoping code. So for instance about the use of anabolic androgenic
      steroids (AAS) by school children or young students. But only few investigations
      point to the drug abuse in mass sport regarding the easily accessible over-the
      counter drugs of the class of nonsteroidal anti-inflammatory drugs (NSAID). These
      drugs permit an athlete to compete at his normal level of performance despite
      injuries or pain. However, the masking of pain may exacerbate the injury.
      Precautions should be taken to prevent the unwarranted or unmonitored use of anti
      inflammatory agents during treatment of sport injuries. The abuse may be
      extensive since most people consider over-the-counter drugs, such as aspirin and
      ibuprofen, harmless. Studies in Switzerland among endurance athletes in mass
      sport examining the use of medications before an event showed a prevalence
      between 5 and 10% of NSAID. Even if this seems a small number, further
      investigations should focus on the use of medications among different age groups
      and preventive information to abstain from the use of certain medication for
      competitors in mass sport should be worked out.

PMID- 11344956
TI  - ["Doping and ethics"--a traditional and obviously never ending subject! Why is it
      so difficult to act ethically responsibly also in sports?].
AB  - Everybody knows that doping is not allowed. Whether doping is also unethical is
      less clear. To use doping agens as long as they are prohibited is clearly
      unethical. But why do we have to ban doping agens? This needs some reflections
      and has to be discussed all the time!

PMID- 11344957
TI  - [Acute kidney failure in systemic vasculitis associated with antineutrophil
      cytoplasmic antibodies (ANCA) in aged patients].

PMID- 11344958
TI  - [Adrenomedullin: a new vasoactive peptide].

PMID- 11344959
TI  - [Adynamic bone disease and relative hypoparathyroidism in uremia].

PMID- 11344960
TI  - [Use of personal digital assistants (PADs) in medicine].

PMID- 11344961
TI  - [Vascular access in Spain: analysis of its distribution, morbidity, and
      monitoring systems].
AB  - Vascular access disfunction causes a therapeutic emergency with different
      implications in patients and care givers. The aim of this study was to know the
      distribution of different kinds of vascular access between prevalent hemodialysis
      patients, the proportion of incident patients that holds a permanent vascular
      access, the monthly hospital ratio for access repair and the use of surveillance
      systems of vascular access adequacy in the different Centers. This is a National
      survey that shows results of a questionnaire sent to all hemodialysis units in
      Spain on september 1999. Eighty-eight units answered the questionnaire (42%)
      providing information about 5,476 prevalent patients. Of these patients, 81%
      receives treatment through an arteriovenous fistula, 10% uses a central catheter
      and 9% a graft. Only 56% of incident patients have a permanent vascular access.
      Reasons for catheter use between prevalent patients were exhaustion of vascular
      sites in 42%, maduration of permanent access in 24%, thrombosis of the access in
      14% and another reasons in 19%. Patients monthly hospitalization ratio for
      vascular repair was 3%, that might represent more than 5,600 hospital ingress by
      year. More than 80% of the Units releases different surveillance programs of
      access adequacy, 69% by fiscal detection problems, 47% by dynamic alterations and
      18% by dilution and imaging procediments. The conclusions of this survey are that
      arteriovenous fistula is the most used vascular access in Spain. Almost half of
      the patients do not have vascular access in use for the beginning of
      hemodialysis. Exhausted vascular sites is the primary reason for central catheter
      using. A great proportion of Units are employing programs for access monitoring.

PMID- 11344962
TI  - [Effects of carvedilol in rats with induced chronic kidney failure].
AB  - Hypertensive mechanisms are postulated to play a major role in the progressive
      glomerulosclerosis (GS) after renal mass reduction. Previous studies have
      demonstrated differences in the progression to glomerulosclerosis with the use of
      different antihypertensive drugs. We analyzed whether the use of carvedilol
      (CVD), a new beta-adrenoceptor antagonist and vasodilator slows the progression
      of glomerulosclerosis in 5/6 nephrectomised (Nx) rats. Fifty-four adult Sprague
      Dawley rats were distributed among five groups, four with 5/6 Nx, vehicle treated
      and CVD at 5, 10 and 20 mg/kg/day and sham (no renal ablation or drug treatment).
      Tailcuff blood pressure, serum creatinine and urine protein concentration were
      measured. At the end of the experiment remnant kidney was removed for
      morphometric studies. Rats treated with 10 and 20 mg/kg/day of CVD showed
      controlled systemic blood pressure. Serum creatinine was similar in all treated
      groups with CVD, and half the levels observed in the vehicle-treated rats. The
      prevalence of glomerular lesions was closely associated with the degree of
      proteinuria. Eleven weeks after 5/6 Nx, vehicle-treated rats exhibited marked GS
      with 76% of affected glomeruli and creatinine retention. By contrast, renal
      injury was largely prevent in those rats treated with 10 and 20 mg/kg/day of CVD.
      Tuft enlargement occurred in all groups but was more prominent in vehicle-treated
      group, 1.5 times higher than the group treated with 20 mg/kg/day of CVD.
      Although, these data demonstrate the importance of systemic blood pressure
      control in the renal protective efficacy of carvedilol, other less-known
      mechanisms of this drug must be investigated.

PMID- 11344963
TI  - [Cyclosporin A inhibits the response of osmotic water permeability to
      antidiuretic hormone in toad's bladder and to angiotensin II and antidiuretic
      hormone in toad's skin].
AB  - The purpose of the present study was to assess the effects of cyclosporine A
      (CyA) in the osmotic water flow response of isolated toad bladder to arginine
      vasotocin (AVT) and to angiotensin II (Ang II) and AVT in isolated toad skin. CyA
      added to the dermal side of isolated toad skin or to the serosal side of toad
      bladder in concentrations of 0.42. 10(-6) M to 0.42. 10(-7) M had no effect on
      basal osmotic water permeability (Posm) but inhibited the hormonal response to
      AVT in both membranes (AVT 10(-10) M in toad bladder and 10(-8) to 10(-9) M in
      toad skin). CyA also inhibited the Posm response to Ang II (10(-7) M) in toad
      skin in concentrations of 0.42. 10(-6) M and 0.42. 10(-7) M. In toad bladder it
      could be demonstrated that the inhibitory effect was reversible. CyA in
      concentrations of 0.42. 10(-6) M inhibited the Posm response of toad skin to
      theophylline (3.2. 10(-3) M) and to dibutyryl cyclic AMP (6.3. 10(-3) M)
      suggesting an effect distal to the generation of cyclic AMP. These responses
      would support the possibility of a diuretic effect in the mammalian nephron.

PMID- 11344964
TI  - [Usefulness of ambulatory blood pressure monitoring in kidney disease].
AB  - High blood pressure is both a cause and a manifestation of renal disease. It has
      an increasing prevalence among renal patients renal function is declining. Blood
      pressure is not a constant value, but it shows a high intrinsic and extrinsic
      variability. It is common to find striking discordances between blood pressure
      values and target organ damage. The average values obtained through ambulatory
      blood pressure monitoring (ABPM) are better related with cardiovascular morbility
      and mortality than office measurement, even in renal disease patients. We report
      the experience with ABPM on 51 renal patients. None of them was on renal
      replacement therapy. In 7 out of 14 non treated patients ABPM showed clinic
      hypertension only. Mean age of truly hypertensive patients was higher, but this
      difference was not significant (normotensive 31.7 +/- 17.1; hypertensive 49.4 +/-
      17.9 years, p < 0.1). There were no sex differences (normotensive, 5 males and 2
      females; hypertensive, 4 males and 3 females). Three normotensive patients had
      chronic renal failure, and as did 6 hypertensive patients (p < 0.1). There were
      no differences in night-time drop either for systolic (normotensive 3.7 +/- 3.5
      hypertensive 6.1 +/- 8.9%) or for diastolic blood pressure (normotensive 10.4 +/-
      4.7 hypertensive 6.2 +/- 8.9%). Thirty-seven patients who were on
      antihypertensive drug treatment: 23 (68.2%) showed hypertension after the ABPM
      and 14 (37.8%) have normal blood pressure values, more over, 4 of these 14
      patients showed hypotension. There were neither age differences between the
      groups (normotensive 49.0 +/- 12.5, hypertensive 51.9 +/- 15.4 years), nor sex
      differences (normotensive 9 males and 5 females, hypertensive 11 males and 12
      females). The prevalence of renal failure was similar (normotensive, 85.7%;
      hypertensive, 82.6%). Mean night-time drop was not different (SBP, normotensive
      6.1 +/- 7.6 hypertensive 7.2 +/- 7.6%; DBP, normotensive 9.0 +/- 8.3 hypertensive
      13.5 +/- 7.6%). ABPM is a helpful diagnostic tool in renal disease as in the non
      complicated essential hypertension patient, both for experimental and for
      clinical purposes.

PMID- 11344965
TI  - [Assessment of salt intake in hemodialysis].
AB  - One of the main goals of dialysis is to reach a correct sodium balance. Dietary
      sodium restriction facilitates control of thirst, water overload, hypertension
      and cardiac failure. Nowadays, it is possible to estimate sodium mass transfer
      and known interdialytic salt intake, by means of non-invasive methods. The use of
      dialysate sodium profiles improves dialysis tolerance but it has been reported
      that interdialytic thirst may increase because of an inappropriate sodium
      balance. The aim of this study was to evaluate the usual salt intake in
      hemodialysis patients, the effects on interdialytic gain weight, arterial
      pressure, blood volume preservation and dialysis tolerance of two different
      profiles of dialysate sodium and an additional session with salt restriction.
      Seventeen dialysis patients, 12 male and 5 females, were studied. Each patient
      underwent seven hemodialysis treatments: three consecutives sessions (a week)
      with constant sodium and ultrafiltration hemodialysis; three consecutive sessions
      with exponential decrease of conductivity (Initial 15.5-16.0, mid-session 14.3
      and at the end 13.9-14 mS/cm) and ultrafiltration (1.6 l/h initial and 0.1 at the
      end) profiled hemodialysis; and an additional session which had a special dietary
      salt restriction. Dialysis parameters and dry weight were kept constant. Integra
      monitor with Diascan and Hemoscan biosensors (Hospal) were used in all sessions.
      We measured pre- and postdialytic plasma conductivity, sodium mass transfer,
      interdialytic weight gain, mean arterial pressure (MAP), percent reductions of
      blood volume (%R-BV) and hypotensive episodes during dialysis. Mean sodium mass
      transfer was 1,144 +/- 356 mmol (no profile week) vs 1,242 +/- 349 mmol (week
      with profiles), NS. It was equivalent to a salt ingestion of 9.6 +/- 3 and 10.4
      +/- 3 g/day respectively. End plasma conductivity was 14.04 +/- 0.14 (no profile)
      versus 14.21 +/- 0.08 mS/cm (profiled), p < 0.001. Interdialytic weight gain was
      2.49 +/- 0.76 (no profile) vs 2.32 +/- 0.56 kg (profiled), NS. MAP was 101 +/- 11
      (no profile) vs 99 +/- 10 mmHg (profiled), NS. The %R-BV was -7.73 +/- 3 (no
      profile) vs -6.46 +/- 3% (profiled), p < 0.01. Hypotensive episodes/session were
      0.66 +/- 0.75 (no profiles) vs 0.41 +/- 0.57 (profiled), NS. Mean sodium mass
      transfer was 356 +/- 125 mmol with usual salt intake and 240 +/- 81 mmol with
      salt restriction, p < 0.001. It was equivalent to a salt ingestion of 10.47 +/- 3
      versus 7.06 +/- 2 g per day respectively, p < 0.001. Initial plasma conductivity
      was 14.31 +/- 0.21 (usually sodium intake) versus 14.16 +/- 0.17 mS/cm (salt
      restriction), p < 0.01. Predialysis blood pressures were decreased with dietary
      salt restriction, MAP was 99.1 +/- 11 vs 94.4 +/- 12 mmHg (p < 0.01).
      Interdialytic weight gain decreased with salt restriction, 2.32 +/- 0.76 vs 1.78
      +/- 0.49 kg (p < 0.001). The %R-BV was -7.25 +/- 2 (usual sodium intake) vs -5.91
      +/- 2% (salt restriction), p < 0.01. Hypotensive episodes/session were 0.71 +/-
      0.8 (usual sodium intake) vs 0.18 +/- 0.5 (salt restriction), p < 0.05. In
      conclusion, automatic measurement of sodium mass transfer is a practical tool to
      follow dietary salt ingestion in hemodialysis patients. It allows us accurate,
      individualised and continual dietary interventions. The use of exponential
      decrease sodium profiles improve dialysis tolerance without changes in sodium
      balance, interdialytic weight gain or arterial pressure. A reduction of three g
      in salt intake observed in this study was beneficial in interdialytic weight
      gain, dialysis tolerance and blood pressure control.

PMID- 11344966
TI  - [Estimate of the dialysis dose using ionic dialysance].
AB  - The Diascan equipment (Hospal) measures ionic dialysance from which it derives
      the Kt/V. It is automatic, does not need blood samples and displays the results
      in real time. The aim of the present study was to compare the Diascan Kt/V with
      the Kt/V obtained with four simple formulas: two based on a single pool model of
      urea kinetics (Lowrie 1983 and Daugirdas 1993) and the other based on the two
      pool model (Maduell formulation applied to Lowrie Kt/V and that proposed by
      Daugirdas 1995). We have analyzed the inter-method variability, the degree of
      relationship among the different procedures for Kt/V calculation and the intra
      individual variability. The intermethod variability between Kt/V Diascan and Kt/V
      calculated by the four simple formulas were studied in one hemodialysis session
      in 19 patients. The Kt/V Diascan was statistically different from that calculated
      by the four formulas (1,021 +/- 0.140 Diascan vs 1,147 +/- 0.124 for Lowrie-83;
      vs 1,373 +/- 0.164 for Daugirdas-93; vs 0.963 +/- 0.105 for Maduell and vs 1,173
      +/- 0.143 for Daugirdas-95, p < 0.01). The lowest inter-method variability was
      obtained with the Maduell's Kt/V (relative difference 9%) but even in this case
      37% of patients had a variability above 10%. The correlation coefficient was not
      high enough to allow an estimation of the different Kt/V measurements from the
      Diascan Kt/V by a regression equation. To study the individual relationship
      between the Diascan Kt/V and the Kt/V calculated by the four formulations, we
      have determined the Kt/V every 30 minutes in one hemodialysis session in 30
      patients. In all patients we observed a good relationship between the Diascan
      Kt/V and the other four (correlation coefficient of 0.9952 for Lowrie-83, 0.9976
      for Daugirdas-93, 0.9961 for Maduell and 0.9971 for Daugirdas-95); with these
      correlation coefficientes it was possible to derive regression equations and to
      obtain an estimation of the four Kt/V's from the Diascan Kt/V. To study the
      individual variability of each procedure used in the Kt/V calculations we
      determined the coefficient of variation of the different methods in 5 consecutive
      hemodialysis sessions performed under identical conditions in 19 patients. The
      coefficient of variation was 3.7 +/- 1.8% for the Diascan Kt/V; 6.0 +/- 2.8 for
      the Lowrie-83 Kt/V; 5.8 +/- 2.4 for the Daugirdas-93 Kt/V; 6.5 +/- 2.6% for the
      Maduell Kt/V; and 5.7 +/- 2.2% for the Daugirdas-95 Kt/V (p < 0.01 between the
      Diascan Kt/V and the other four). CONCLUSIONS: Although the Diascan Kt/V was
      statistically different from the other four Kt/V's calculated by the usual
      formulas, the Diascan Kt/V has an excellent correlation with all of them and
      showed a lower intra-individual variability. It is possible to obtain an
      estimation of the calculated Kt/V for each patient by linear regression equation.

PMID- 11344967
TI  - [Preeclampsia and peripartum cardiomyopathy: infrequent association].
AB  - Peripartum cardiomyopathy (PPCM) is a rare form of congestive heart failure that
      affects women late in pregnancy or in the early puerperium. PPCM is a disorder of
      unknown etiology that can have potentially devastating consequences. Although the
      etiology of PPCM remains unclear, a number of risk factors for this disorder have
      been proposed. However, the disease can occurred in women without these risk
      factors. Preeclampsia is associated with PPCM. However, cardiomyopathy is an
      infrequent complication of preeclampsia. Treatment of PPCM is similar to that
      other types of congestive heart failure. The pregnancy outcome is uncertain.
      Probably it depends on whether ther heart size returns to normal. We present the
      case of a 38 years old woman, who developed in an 33rd week of gestation a PPCM.
      She had some risk factors (include preeclampsia) but had a favorable evolution
      with conventional treatment. The rarity of the syndrome, its potential
      consequences, and the probable association with preeclampsia, stimulated us to
      present this case.

PMID- 11344968
TI  - [Remission of nephrotic syndrome caused by renal amyloidosis secondary to
      pulmonary tuberculosis after tuberculostatic treatment].
AB  - Secondary systemic amyloidosis is a frequent complication in several chronic
      infectious and inflammatory states.  Although initially amyloidosis was described
      in association with long-standing syphilis and tuberculosis, with the
      introduction of antiboitic and antituberculous therapy, rheumatoid arthritis is
      now the commonest cause of this illness.  We present here the case of a 16 year
      old woman, who was diagnosed one month ealier with pulmonary tuberculosis.  She
      developed a nephrotic syndrome and her kidney biopsy confirmed the presence of
      amyloid.  Treatment of the tuberculosis was accompanied by clinical remission of
      the nephrotic syndrome two years later.

PMID- 11344969
TI  - [Risk factors in the development and progression of end-stage renal failure, the
      21st century epidemic].

PMID- 11344970
TI  - [Acute kidney failure induced by rifampicin].
AB  - A case of acute renal failure requiring dialysis and associated with a
      characteristic, fulminant clinical course following the intermittent
      administration of rifampicin is presented. Renal biopsy showed severe tubular
      injury and a mild interstitial mononuclear cell infiltrate. Withdrawal of
      rifampicin led to a compete resolution of renal injury. We review the literature
      on the pathogenesis and treatment of this syndrome and we discuss the different
      substrates for acute renal failure induced by rifampicin.

PMID- 11344971
TI  - [Neurotoxicity caused by ciprofloxacin in hemodialyzed patient].

PMID- 11344972
TI  - [Acute kidney failure caused by phenazopyridine overdose].

PMID- 11344973
TI  - Wound healing.
AB  - Wounds and wound healing have been studied in the medical arena for centuries,
      however, in recent decades new advances have emerged in this extensive field.
      Currently, the wound healing process is studied at the molecular level giving new
      insights to the physiological process of wound closure and the lack thereof. With
      development of new treatment modalities the potential for earlier wound closure
      and ultimately increased quality of life for chronic wound patients is emerging.
      As understanding of the delicate balance of molecules within the wound increases,
      options for treating patients will also increase. Again, an understanding of the
      wound healing process is vital not only when employing these new treatment
      options, but also for proper patient care.

PMID- 11344974
TI  - Bone grafting. Principles and applications in the lower extremity.
AB  - Bone grafting techniques have progressed in the twentieth century, leading to
      results that are more predictable. A complete understanding of the entire healing
      process has broadened indications while decreasing complications. Numerous
      possibilities are available to the foot and ankle surgeon for reconstruction or
      trauma scenarios. Combining the art (knowing when to use specific grafting
      techniques) with the science of graft healing will provide satisfactory results.

PMID- 11344975
TI  - Hypertrophic scars and keloids.
AB  - Excessive scarring caused by pathologically overabundant collagen deposition is a
      problem known by all surgeons. Complications to wound healing, such as
      hypertrophic scars and keloids, can lead to an aesthetically unacceptable result
      or even lead to anatomic dysfunction. An overwhelming amount of hypotheses
      concerning treatment of these problems is available. There seems to be no
      absolutely effective treatment for hypertrophic scars and keloids and the number
      of treatment modalities illustrate the lack of understanding concerning this kind
      of pathologic scar healing. Most studies reported have not been well controlled
      and have produced conflicting results.

PMID- 11344976
TI  - Articular cartilage transplantation. Current and future limitations and
      solutions.
AB  - The ultimate goal of replacing cartilage with a bioengineered graft, autologous
      graft, or allograft is to replace the damaged articulating surface with tissue
      containing the anatomical, biomechanical, and functional properties of native
      articular cartilage, which will have resultant satisfactory clinical outcome. For
      transplanted articular cartilage to obtain the original histologic arrangement of
      hyaline cartilage with secure incorporation into host tissue, progressive
      integrated multidisciplinary research must continue. Although autologous
      chondrocyte transplantation of the talus is not yet FDA approved, this technique
      may provide the surgeons with a cutting-edge method to treat patients with
      nondegenerative osteochondral lesions of the talus and possibly other
      articulating joints of the foot.

PMID- 11344977
TI  - Full-thickness burn of the foot: successful treatment with Apligraf. A case
      report.
AB  - Burn wounds, although uncommon in the foot, present a uniquely challenging
      opportunity to physicians. The keys to successful management include a proper and
      specific initial evaluation of the burning agent, the location, the TBSA
      affected, and the depth. Ultimately, proper recognition and meticulous wound care
      with skin grafting, when necessary, bring about the desired results. A case
      report of a patient with a third-degree burn over the dorsum of the left foot is
      presented. This case is unique in that Apligraf, a human skin equivalent, was
      used to gain coverage and eventual resolution of the wound. It is the authors'
      opinion that the use of Apligraf in this application is a viable alternative to
      traditional methods of skin harvesting and grafting. To the authors' knowledge,
      there have been no other cases reported of Apligraf use in burn wound coverage of
      the foot.

PMID- 11344978
TI  - The use of becaplermin (rhPDGF-BB) gel for chronic nonhealing ulcers. A
      retrospective analysis.
AB  - Chronic, nonhealing wounds have plagued health care practitioners for decades.
      New research and technology have allowed the wound healing process to be
      understood at a cellular and molecular level, including the vital role of growth
      factors. This article discusses the effects of platelet-derived growth factor-BB
      (PDGF-BB) on the wound healing process, emphasizing the inflammatory stage of
      wound healing and principles of wound care. Preclinical and clinical studies
      evaluating recombinant human PDGF-BB (rhPDGF-BB) (becaplermin gel) also are
      discussed. Lastly, the results of a retrospective analysis evaluating the use of
      rhPDGF-BB at Broadlawns Medical Center (Des Moines, IA) are presented.

PMID- 11344979
TI  - Articular cartilage. Anatomy, injury, and repair.
AB  - Articular cartilage plays a vital role in joint morphology. An understanding of
      articular cartilage anatomy and physiology will enable the physician to more
      fully appreciate its function and necessity. Articular cartilage is made up of
      four basic biological layers or zones. Each zone possesses attributes necessary
      to make articular cartilage as a whole strong, durable, and more able to
      withstand shear and axial forces through a joint. Cartilage metabolism is
      relatively slow in comparison with other tissues; hence, it is much more
      difficult for defects in cartilage to heal spontaneously. There are many ways in
      which articular cartilage can incur damage. Mechanical injury, be it acute or
      insidious, causes cartilage to fissure and fracture. This results in painful and
      inflamed joints along with disruption of the cartilage. Metabolic diseases also
      can produce joint destruction, inflammation, and pain. The resultant defects fail
      to heal spontaneously because of slow metabolism of cartilage. These chondral
      defects eventually may penetrate subchondral bone. Disruption of the layers of
      cartilage eventually will cause collapse and loss of integrity of the entire
      joint apparatus as a whole. More than 250 years ago, Hunter stated, "Ulcerated
      cartilage is a troublesome thing--once [it is] destroyed it is not repaired."
      Articular cartilage defects are very difficult to repair effectively. Cartilage
      defects can heal spontaneously, if the defect extends to subchondral bone. The
      reparative substance, fibrocartilage, is less durable and much less smooth. There
      are many techniques and procedures in which chondral or osteochondral defects can
      be filled. Promoting subchondral bleeding is the method most commonly used
      clinically. This allows pleuripotent cells to fill the defect with eventual
      fibrocartilage. Implants are gaining favor as a method of inducing a more pure,
      hyaline-like cartilage into cartilage defects. Gene therapy and tissue
      engineering are at the forefront of cartilage research today. Cartilage injury
      and repair remains today a very difficult topic of study. Understanding the
      anatomy of articular cartilage, the pathomechanics of injury, and methods
      available for cartilage repair, will help the physician more adequately approach
      treatment options.

PMID- 11344980
TI  - Current concepts of bone healing.
AB  - The intent of this article is to present the current understanding of fracture
      repair and offer investigative evidence to the use of exogenous growth factors
      enhancing fracture healing. The authors believe that exogenous growth factors
      have tremendous clinical applications and will continue to influence bone healing
      in the future. With the expanding knowledge of the intricate molecular and
      cellular biology of fracture repair being realized, surgeons will be able to
      enhance and ensure healing of surgical osteotomies, fractured bone ends, or
      delayed unions. This field of medicine is continuously growing and the
      possibilities seem endless.

PMID- 11344981
TI  - Electrical stimulation with bone and wound healing.
AB  - Electrical stimulation has been used to heal fractures and ulcers and reduce pain
      through modulation of local body processes. It has been recognized that
      mechanical forces and bioelectricity have an intimate relationship in influencing
      the production of bone. Science has developed techniques to affect change in the
      electrical charge of fractures to positively affect the healing process.
      Electrical stimulation, through invasive and noninvasive applications, has
      produced excellent results in the treatment of nonunions and ulcer care. A
      thorough review of the electrical properties of bone and soft tissue and the
      influence of electrical stimulation on healing is presented here.

PMID- 11344982
TI  - Bone healing in children.
AB  - Just as pediatric fractures and bones are basically similar to adult fractures
      and bones, pediatric bone healing is basically similar to adult bone healing.
      They both go through the three same phases of inflammation, reparation, and
      remodeling. It is those differences between pediatric and adult bone, however,
      that affect the differences in the healing of pediatric bone. Because pediatric
      bone can fail in compression, less initial stability and less callus formation is
      required to achieve a clinically stable or healed fracture. The greater
      subperiosteal hematoma and the stronger periosteum all contribute to a more rapid
      formation of callous strong enough to render the fracture healed more rapidly
      than the adult. Genes and hormones that are necessary for the initial formation
      of the skeleton are the same as, or at least similar in most instances, to those
      necessary for the healing of fractures. This osteogenic environment of the
      pediatric bone means that these fracture healing processes are already ongoing in
      the child at the time of the fracture. In the adult, these factors must be
      reawakened, leading to the slower healing time in the adult. Once the fracture is
      healed, the still-growing pediatric bone can correct any "sins" of fracture
      alignment or angulation leaving the bone with no signs of having ever been
      broken. The final result is bone that is, in the child's words, "as good as new."

PMID- 11344983
TI  - Biology of HIV-1 in women and men.
AB  - The HIV epidemic continues to spread worldwide, particularly among women and
      nonwhites. Development of vaccines and improved treatments depend on
      understanding pathogenesis. In the past few years, studies have begun to focus on
      HIV-1 pathogenesis in women, in whom some differences have been found in
      comparison with men. Attention is now focused on HIV-1 infection in reservoirs
      other than blood, particularly the genital tract. In addition, study of the
      genetic determinants of susceptibility to HIV-1 infection, including the
      chemokine receptors, have provided knowledge useful for the design of new
      treatments.

PMID- 11344984
TI  - HIV in the female genital tract: viral shedding and mucosal immunity.

PMID- 11344985
TI  - Pregnancy and infection with human immunodeficiency virus.
AB  - During the past decade, there has been a dramatic increase in the number of women
      infected with HIV and the number of women with clinical AIDS. One of the most
      prominent features of HIV infection is that it is usually diagnosed during the
      peak reproductive years, and in 1998, HIV/AIDS was the fourth leading cause of
      death among women between the ages of 25 and 44 years. For this reason, there has
      been long-standing concern regarding the obstetric implications of HIV infection:
      both the impact of pregnancy on possibly accelerating the course of HIV disease
      and the impact of HIV infection on the course of pregnancy. There appears to be
      some immunologic changes associated with pregnancy, but they are not dramatic,
      and immune markers generally resume their prepregnancy values after delivery.
      With regard to long-term effects of pregnancy on HIV disease progression, no
      study to date has shown significant increases in mortality or in AIDS incidence
      associated with pregnancy. Studies have generally been small, however, and none
      have accounted for antiretroviral therapy usage. Many studies have shown that
      certain adverse outcomes are more common in HIV-positive pregnant women as
      compared with HIV-negative pregnant women, and concerns have been raised that
      spontaneous abortions may be more common among HIV-infected women and that this
      may impact fertility rates. Although important understanding has been acquired
      regarding the associations between pregnancy and the course of HIV infection,
      much remains to be understood. Additional, well-designed studies are clearly
      needed to rigorously address the many remaining questions that exist. We can
      anticipate that the resolution of these questions will continue to be of broad
      public health interest as the epidemic impacts increasing numbers of women, a
      large fraction of whom will be adolescents.

PMID- 11344986
TI  - Selected issues in the treatment of women infected with HIV.

PMID- 11344987
TI  - Maternal therapy for HIV in pregnancy.

PMID- 11344988
TI  - Determinants of transmission of HIV from mother to child.

PMID- 11344989
TI  - Prevention of mother-to-child transmission of HIV.

PMID- 11344990
TI  - Gynecologic care of women infected with HIV.

PMID- 11344991
TI  - Pediatric HIV infection.

PMID- 11344992
TI  - Management of needlestick injuries.

PMID- 11344993
TI  - Sexual and reproductive behavior of women with HIV infection.

PMID- 11344994
TI  - Ethical and legal issues in perinatal HIV.

PMID- 11344995
TI  - Epidemiology of uterine leiomyomata.

PMID- 11344996
TI  - Identification of new therapies for leiomyomas: what in vitro studies can tell
      us.
AB  - Leiomyomas are a significant problem in women's health. An understanding of the
      biology of these tumors and how their growth is regulated is emerging from in
      vitro studies using tissue specimens and cultured cells. These studies have
      clarified how the ovarian steroid hormones regulate growth of uterine SMCs and
      how the ovarian steroid ligand-receptor system has been altered in leiomyomas.
      Such information will allow investigators to identify steroid hormone antagonists
      and steroid hormone receptor modulators that may be useful for treatment of
      leiomyomas. We are now also developing a much better understanding of the growth
      factors that are produced by SMCs of leiomyoma tumors. These growth factors not
      only regulate the proliferation, apoptosis, and extra-cellular matrix production
      of the SMCs but also regulate proliferation and migration of vascular endothelial
      cells. Targeting these growth factors and their receptors can reduce leiomyoma
      growth through two different mechanisms. One targets the SMCs and the other
      targets the vascular system that supports the growth of the tumor. Another
      important lesson that can be learned from reading the scientific literature is
      that there are striking similarities between the biology of uterine leiomyomas
      and other pathologic diseases that involve mesenchymally derived cells. These
      include benign keloids, other fibrotic diseases such as pulmonary fibrosis, and
      vascular diseases such as atherosclerosis. Compounds that are developed to treat
      these conditions may also be beneficial for treatment of uterine leiomyomas. The
      next few years will undoubtedly yield many new drug discoveries for these
      diseases.

PMID- 11344997
TI  - Genetics and the development of fibroids.

PMID- 11344998
TI  - Pathology of smooth muscle tumors of the uterine corpus.

PMID- 11344999
TI  - Clinical symptomatology of uterine leiomyomas.

PMID- 11345000
TI  - Traditional surgical approaches to uterine fibroids: abdominal myomectomy and
      hysterectomy.
AB  - Abdominal myomectomy and hysterectomy remain the traditional treatment of large
      symptomatic uterine myomas. The preoperative indications for abdominal myomectomy
      or hysterectomy must be clearly evaluated and delineated avoid unnecessary
      intervention. There appears to be an increasing trend toward expectant management
      for asymptomatic uterine myomas. Women should consider the options of myomectomy
      and hysterectomy when their symptoms are severe enough to warrant intervention
      and the benefits of intervention outweigh the risks. The advantages and
      disadvantages of preoperative medical also must be addressed before intervention.
      The factors influencing the choice of therapy seem to be strongly dependent on
      both the patient and physician preferences. A clinical approach to abdominal
      myomectomy in patients with infertility and repetitive miscarriage has been
      presented in this chapter. The rapid development and use of minimally invasive
      innovations and adjunctive medical therapies has provided clinicians with a
      wealth of alternatives. A practical and cost-effective approach based on the data
      currently available have been presented; however, there remains a paucity of
      prospective randomized data to evaluate and compare the effectiveness and safety
      of these alternative treatments to abdominal myomectomy and hysterectomy. Future
      studies should help define the optimal candidates for traditional surgical
      treatment with abdominal myomectomy and hysterectomy.

PMID- 11345001
TI  - Laparoscopic approaches to uterine leiomyomas.

PMID- 11345002
TI  - Uterine artery embolization for uterine fibroids: a radiologist's perspective.

PMID- 11345003
TI  - Gene therapy and uterine leiomyomas.

PMID- 11345004
TI  - Anatomy of the peripheral nervous system.
AB  - This article is an overview of the structure and components of the peripheral
      nervous system. The fine structure and gross anatomy of peripheral nerves and
      ganglia are described. A functional and regional approach is used to highlight
      principles on which the peripheral nervous system is designed. Finally, the
      somatic and autonomic nervous systems are contrasted to underscore similarities
      between the two systems.

PMID- 11345005
TI  - The clinical application of peripheral nerve pathology.
AB  - The basic pathologic processes that can affect the peripheral nerve are
      discussed, with an emphasis on the basic findings seen on nerve biopsy. The
      indications and usefulness of nerve biopsy are discussed along with a review of
      the morphologic findings found with a variety of tissue preparation techniques.
      Advances, such as intradermal biopsies, which may prevent the need for standard
      nerve biopsies, are discussed.

PMID- 11345006
TI  - Electrodiagnostic approach to patients with suspected generalized neuromuscular
      disorders.
AB  - Electrodiagnosis is an important part of the diagnostic evaluation for patients
      with suspected neuromuscular diseases. The electrodiagnostician should maintain a
      broad, inclusive differential diagnosis and tailor the examination using a sound
      conceptual framework. A clear understanding of what is normal provides the proper
      foundation on which to judge electrodiagnostic findings. Many peripheral
      neuromuscular conditions manifest themselves in characteristic ways on EMG and
      nerve conduction testing, making them identifiable to the skilled
      electrodiagnostic medicine consultant.

PMID- 11345007
TI  - Molecular basis of hereditary neuropathies.
AB  - Inherited disorders of peripheral nerves represent a common group of neurologic
      diseases. Charcot-Marie-Tooth neuropathy type 1 (CMT1) is a genetically
      heterogeneous group of chronic demyelinating polyneuropathies with loci mapping
      to chromosome 17 (CMT1A), chromosome 1 (CMT1B) and to another unknown autosome
      (CMT1C). CMT1A is most often associated with a tandem 1.5-megabase (Mb)
      duplication in chromosome 17p11.2-12, or in rare patients may result from a point
      mutation in the peripheral myelin protein-22 (PMP22) gene. CMT1B is associated
      with point mutations in the myelin protein zero (P0 or MPZ) gene. The molecular
      defect in CMT1C is unknown. X-linked Charcot-Marie-Tooth neuropathy (CMTX), which
      has clinical features similar to CMT1, is associated with mutations in the
      connexin32 gene. Charcot-Marie-Tooth neuropathy type 2 (CMT2) is an axonal
      neuropathy, also of undetermined cause. Forms of CMT2 map to chromosome 1p36
      (CMT2A), chromosome 3p (CMT2B), chromosome 7p (CMT2D), and to chromosome 8p21
      (CMT2E). Dejerine-Sottas disease (DSD), also called hereditary motor and sensory
      neuropathy type III (HMSNIII), is a severe, infantile-onset, demyelinating
      polyneuropathy syndrome that may be associated with point mutations in either the
      PMP22 gene or the P0 gene and shares considerable clinical and pathologic
      features with CMT1. Hereditary neuropathy with liability to pressure palsies
      (HNPP) is an autosomal dominant disorder that results in a recurrent, episodic
      demyelinating neuropathy. HNPP is associated with a 1.5-Mb deletion in chromosome
      17p11.2-12 and results from reduced expression of the PMP22 gene. CMT1A and HNPP
      are reciprocal duplication/deletion syndromes originating from unequal crossover
      during germ cell meiosis. Other rare forms of demyelinating peripheral
      neuropathies map to chromosomes 8q, 10q, and 11q. Hereditary neuralgic amyotrophy
      (familial brachial plexus neuropathy) is an autosomal dominant disorder causing
      painful, recurrent brachial plexopathies and maps to chromosome 17q25.

PMID- 11345008
TI  - The role of neurotrophic factors in disorders of peripheral nerves and motor
      neurons.
AB  - Recent, exciting research in neurotrophic factors has significantly enhanced our
      understanding of their actions. Neurotrophic factors have been shown to have
      robust effects on neuronal survival and differentiation in vitro and in vivo and
      have been tested in animal models of human neurologic disorders. These studies
      have encouraged initiation of clinical trials of several neurotrophic factors for
      diseases of peripheral nerves and motor neurons. In this article, the author
      reviews the data for the actions of neurotrophic factors on peripheral nerves and
      motor neurons, the rationale for their use in clinical trails. The results of
      clinical trials of nerve growth factor (NGF), brain-derived neurotrophic factor
      (BDNF), and insulin-like growth factor type 1 (IGF-1), three neurotrophic factors
      that have been tested in phase III studies, are also reviewed.

PMID- 11345009
TI  - Diabetic neuropathies.
AB  - Diabetes mellitus is a systemic disorder with a significant impact on the
      peripheral nervous system. Over half of the 15 million patients with diabetes
      mellitus in the United States have some form of diabetic neuropathy. Individuals
      with diabetes may develop acute or subacute painful polyneuropathy, proximal
      motor neuropathy, autonomic neuropathy, compression neuropathy, focal neuropathy,
      and chronic polyneuropathy. Studies have shown that optimizing diabetic control
      provides the greatest likelihood of either preventing or slowing the development
      of diabetic neuropathy.

PMID- 11345010
TI  - Acquired inflammatory demyelinating neuropathies.
AB  - The acquired demyelinating neuropathies can be divided into those with an acute
      onset and course and those with a more chronic course. The acute neuropathies
      present as Guillain-Barre syndrome and include acute inflammatory demyelinating
      polyradiculoneuropathy (AIDP), Miller Fisher syndrome, acute motor axonal
      neuropathy (AMAN), acute motor and sensory axonal neuropathy (AMSAN), and acute
      pandysautonomia. The chronic neuropathies are collectively known as chronic
      inflammatory demyelinating polyradiculoneuropathy (CIDP) and include MADSAM
      (multifocal acquired demyelinating sensory and motor neuropathy, also know as
      Lewis-Sumner syndrome) and DADS (distal acquired demyelinating symmetric
      neuropathy) as variants. The clinical features, pathology, pathogenesis,
      diagnosis, treatment, rehabilitation, and prognosis of these neuropathies are
      discussed.

PMID- 11345011
TI  - Motor neuron disease.
AB  - Motor neuron disease refers to a spectrum of disorders resulting from
      degeneration of the upper or lower motor neurons or both. Amyotrophic lateral
      sclerosis is the most common form of motor neuron disease, in which patients
      demonstrate evidence of both anterior horn cell (lower motor neuron) and
      corticospinal tract (upper motor neuron) dysfunction. Several theories regarding
      the pathogenesis of amyotrophic lateral sclerosis have emerged, including
      glutamate excitotoxicity, free radical oxidative stress, cytoskeletal
      abnormalities, a deficiency of neurotrophic factor, autoimmunity, apoptosis, and
      viral infection. Numerous clinical trials have been completed based on these
      possible mechanisms of the disease propagation including treatment with
      antiglutamate agents, anti-oxidants, immunosuppressants, and neurotrophic
      factors. Several of these trials have shown modest effects in slowing the disease
      course. None, however, have yielded marked benefit in arresting disease
      progression. The most significant effect in abating disease progression has been
      our use and understanding of aggressive symptomatic therapy to reduce disability,
      enhance quality of life, and improve prognosis.

PMID- 11345012
TI  - Idiopathic shoulder girdle neuropathy.
AB  - Idiopathic shoulder girdle neuropathy is the syndrome of acute upper extremity
      pain located primarily in the shoulder, which is subsequently replaced by
      painless neurologic weakness and sensation loss. The disease is self-limited and
      generally carries with it a favorable prognosis. The clinical presentation,
      electrodiagnostic picture and natural history are discussed.

PMID- 11345013
TI  - Ischemic peripheral neuropathy.
AB  - Ischemic neuropathy from sources other than diabetes is less common, but can be
      encountered in clinical practice. Diagnosis can be challenging, and many patients
      may be referred to the electrodiagnostic laboratory. Overlapping mononeuritis
      multiplex is a common presentation, but distal symmetric polyneuropathy and
      monomelic neuropathy patterns can be seen. Depending on the disease associated
      with ischemic neuropathy, a mononeuropathy or a sensory-motor, axonal
      demyelinating peripheral neuropathy may be seen as well. The treatment of
      ischemic neuropathy varies depending on the associated disease. Prognosis can be
      poor in the case of amyloidosis and the primary vasculitides. The literature is
      limited to cross-sectional case series and rare longitudinal studies likely
      related to the incidence of the diseases. Further study is needed to fully define
      the extent of the neurologic consequences of peripheral ischemia and its
      significance clinically.

PMID- 11345014
TI  - Update on the evaluation and therapy of autoimmune neuromuscular junction
      disorders.
AB  - Many recent strides have increased our understanding of the immune-mediated
      diseases of neuromuscular junction transmission. Nevertheless, patients with
      myasthenia gravis and the Lambert-Eaton myasthenic syndrome often present
      diagnostic and therapeutic challenges to clinicians. Both conditions have a wide
      range of clinical presentations and the number of treatment modalities available
      to these patients continues to increase. This creates a need for an
      individualized approach for managing these patients. Other important
      controversies exist because the benefits of some treatments are not firmly
      established by clinical trials. After a brief review of the pertinent scientific
      basis of these diseases, we focus on present issues governing the clinical
      evaluation and management of myasthenia gravis and the Lambert-Eaton myasthenic
      syndrome.

PMID- 11345015
TI  - Magnetic resonance imaging of the peripheral nervous system.
AB  - An accurate diagnosis is the essential first step toward a successful treatment
      plan in patients who present with pain and suspected nerve entrapment. Pain and
      dysfunction are often related to an acute traumatic event or a classic
      presentation that leads to a straightforward clinical diagnosis. The diagnostic
      approach to abnormalities of the peripheral nervous system always begins with a
      thorough history and physical examination. Imaging may play an important role in
      confirming the initial clinical [figure: see text] diagnosis so that a rational
      plan of treatment may be selected. Diagnostic imaging is especially important
      when there is significant uncertainty regarding the cause of pain and the outcome
      may be improved by timely implementation of various treatment options. Diagnostic
      accuracy is important when various conditions in the differential diagnosis would
      be treated differently from the beginning. Indeed, certain conditions that result
      in pain and dysfunction related to peripheral nerve entrapment are best treated
      with initial rest, protection, and rehabilitation whereas other conditions are
      best treated with prompt surgery. Promptly arriving at an accurate diagnosis is
      an essential step in designing a rational course of therapy, in achieving a good
      outcome, and in treating medical conditions in a timely fashion. Indeed, because
      pain is mediated through peripheral nerves, establishing an accurate diagnosis is
      especially important in disorders of the peripheral nervous system in which there
      may be considerable pain and suffering with an incorrect or delayed diagnosis.
      Moreover, an early diagnosis is desirable [figure: see text] to preserve motor
      power and sensory function in cases of clinically occult nerve entrapment.
      Although entrapment syndromes are well described and widely documented in the
      literature, they may be easily missed in clinical practice in certain instances.
      Although MR imaging is useful to confirm and characterize a known or suspected
      case of peripheral nerve entrapment, there may be evidence of peripheral nerve
      pathology that is first detected with MR imaging. Clinically unsuspected nerve
      entrapment may occur in patients with occult dorsal ganglion cysts in the wrist
      that may entrap the posterior interosseous nerve and produce pain without other
      symptoms. In addition, the authors routinely see patients with paralabral cysts
      secondary to tears of the superior labrum in the shoulder resulting in entrapment
      of the suprascapular nerve. This diagnosis is usually not suspected clinically
      until there is relatively advanced weakness and muscular atrophy in addition to
      shoulder pain. MR imaging remains an evolving technique with ongoing improvements
      in technology and developing clinical experience, resulting in greater diagnostic
      capacity. In this article current technique and strategies for image analysis and
      the authors' specific clinical experience with MR imaging of peripheral nerve
      disorders are reviewed. The exact role of MR imaging in the evaluation of these
      disorders will be further defined with additional experimental work and published
      clinical experience.

PMID- 11345016
TI  - Orthotic management in peripheral neuropathy.
AB  - An appropriate orthosis can improve the function of a patient with peripheral
      neuropathy. It is crucial to be cognizant of the patient's goals, concomitant
      medical conditions, cosmesis, comfort, and functional deficits. In addition, a
      close working relationship with an orthotist will ensure a successful orthotic
      prescription.

PMID- 11345017
TI  - Advances in the management of neuropathic pain.
AB  - Much progress has been made in the assessment and management of neuropathic pain
      over the past 5 years. Assessment has improved with the Neuropathic Pain Scale, a
      new, easily administered, diagnostic tool. Mechanistically, recent studies
      indicate that peripheral neuropathic pain is generated through a focal
      inflammatory process rather than axonal destruction. This process also appears to
      involve mRNA regulation of fast sodium channels, which produce ectopic discharges
      and are presumably responsible for pain generation. In addition the entire
      neuraxis undergoes neuroplastic changes as a result of peripheral nerve injury.
      The available clinical trial data indicate that newer antiepileptic drugs (AEDs),
      most notably gabapentin, are better alternatives to older medications such as
      carbamazepine or phenytoin in the treatment of neuropathic pain. Gabapentin is at
      least as good with respect to actual pain relief as the antidepressants,
      including amitriptyline, but has a much better safety profile with minimal drug
      drug interactions and side effects. Mexiletine is a reasonable alternative agent
      in patients who have not had a satisfactory response to, or cannot tolerate, the
      AEDs or antidepressants. Long-acting opioids should be considered in patients
      refractory to these adjunctive agents. With the advent of the topical lidocaine
      patch, the first drug with an FDA-approved indication for postherpetic neuralgia,
      a revolutionary new agent is now available for the treatment of neuropathic pain
      that does not have any systemic side effects.

PMID- 11345018
TI  - Health-related quality of life in peripheral neuropathy.
AB  - It is now possible for the clinician to use multidimensional measures to assess
      the quality of life of their patients. Some of the more widely used instruments
      to measure HRQOL are the Medical Outcomes Study Short Form 36, the Nottingham
      Health Profile, the Sickness Impact Profile, and the World Health Organization
      Quality of Life instrument. Potential uses of quality of life assessment tools
      include: (1) monitoring the health and social status of a given population, (2)
      evaluating health care policy, (3) conducting clinical trials, (4) assessing the
      effectiveness of rehabilitation services, (5) justifying the allocation of
      limited social and health care resources, and (6) tailoring management to the
      needs of the patient.

PMID- 11345019
TI  - Peripheral neuropathies of childhood.
AB  - This article has provided a brief overview of the most common inherited and
      acquired peripheral nerve diseases encountered in childhood. The diagnostic
      approach of peripheral neuropathies in children often relies on some combination
      of careful history taking, physical examination findings, a careful determination
      of family history, electrodiagnostic studies, molecular genetic studies, sural
      nerve biopsy, and occasionally metabolic laboratory studies. Although pediatric
      mononeuropathies may have different causes than those observed in adults, the
      clinical presentations, diagnostic evaluation, and management of mononeuropathies
      are frequently similar in adults and children. Encouraging progress is being made
      in the management of acute inflammatory demyelinating polyneuropathy (AIDP),
      which is the most common acquired neuropathy of childhood. Rapid advances in
      molecular genetics over the past decade have had a significant impact on our
      diagnostic approach to hereditary motor sensory neuropathy in particular. In the
      future it is likely that the sequencing of genes, characterization of protein
      structure and function, and further elucidation of pathophysiology will have
      significant impacts on the treatment of many inherited peripheral neuropathies of
      childhood.

PMID- 11345020
TI  - Induced apoptosis in human prostate cancer cell line LNCaP by Ukrain.
AB  - Exposure of LNCaP prostate cancer cells to Ukrain (NSC-631570), a novel
      semisynthetic drug from Chelidonium majus L., results in cell growth inhibition
      which is concomitant with apoptosis. After 24 h treatment with 3.5 microM of
      Ukrain as many as 73% cells were found in the G2/M phase. However, at higher drug
      concentrations (7 microM and 17.5 microM) the changes in cell phase distribution
      were less dramatic but cell accumulation in the G2/M phase was still evident. The
      rate of apoptotic cells rose steadily with increased drug concentration in a dose
      dependent manner and reached 20% at a dosage of 17.5 microM. To investigate
      whether the cell cycle control mechanisms are affected in response to Ukrain, we
      analyzed the expression levels of some cyclins, cyclin-dependent kinases (CDK)
      and apoptosis-related proteins in drug treated cancer cells. Western blot
      experiments revealed alterations in levels of CDK1 and CDK2, after treatment. Up
      regulation of the CDK inhibitor p27 was observed, which may lead to G2/M cell
      accumulation, but no substantial changes in expression of Bcl-2 and Bax proteins
      were found.

PMID- 11345021
TI  - Bcl-2 overexpression protects human keratinocyte cells from Ukrain-induced
      apoptosis but not from G2/M arrest.
AB  - Exposure of ME180 and A431 carcinoma cells to Ukrain (NSC-631570), a
      semisynthetic compound consisting of alkaloids isolated from Chelidonium majus L.
      (Papaveracea), results in cell cycle arrest at the G2/M phase. Ukrain selectively
      inhibits growth of ME180 and A431 cells at a concentration range from 3.5 microM
      to 7.0 microM and induces apoptosis. In contrast, normal human keratinocytes
      showed no difference in the kinetics of progression through the cell cycle in
      response to this compound. We found that at a concentration of 7.0 microM of this
      drug Bcl-2 protein overexpression protected HaCaT cell line keratinocytes against
      apoptosis induced by Ukrain but did not prevent G2/M arrest. Following exposure
      of normal keratinocytes to Ukrain, we detected an increase in Bcl-2 protein
      levels and a significant change in protein modification as suggested by
      observation of its different isoform with shifted electrophoretic mobility. Bcl-2
      protein expression and its isoform distribution did not change substantially in
      ME180 and A431 carcinoma cells. We also suggest that drug-induced mitotic arrest
      and apoptosis represent dual Ukrain action on cell cycle progression machinery
      and Bcl-2-involved program cell death in the cell.

PMID- 11345022
TI  - Ukrain: acute toxicity after intravenous, intramuscular and oral administration
      in rats.
AB  - The acute toxicity of Ukrain (1 g/30 ml) was determined after a single
      intravenous, intramuscular or oral administration in rats, performed in
      accordance with Good Laboratory Practice and the relevant European Community
      directive. Groups of five (male and/or female) Him:OFA rats were treated once
      with the following doses: intravenous route: 1.0 ml/kg (males and females), 1.7
      ml/kg (males and females) and 3.0 ml/kg (females); intramuscular route: 5.0 ml/kg
      (males and females); oral route: 15.0 ml/kg (females), 27.0 ml/kg (males and
      females) and 50 ml/kg (females). The animals were kept for up to 14 days
      afterwards while clinical observations and body weight determinations were made
      and were then necropsied. An intravenous injection of Ukrain (1 g/30 ml) induced
      immediate effects (short-term unconsciousness, followed by cardiovascular signs
      and, later, signs of general malaise), which if not lethal, disappeared in a
      short time. It was found that the intravenous LD50 was greater than 43 mg active
      ingredient/kg body weight in the males and 76 mg active ingredient/kg body weight
      in the females. An intramuscular injection of Ukrain (1 g/30 ml) in the maximum
      technically feasible dose induced some transient signs of minor clinical
      importance which did not become life threatening. In both sexes the intramuscular
      LD50 was greater than 165 mg active ingredient/kg body weight.

PMID- 11345023
TI  - A method for determination of Ukrain in blood plasma for monitoring and
      pharmacokinetic study.
AB  - We developed a method using high-performance liquid chromatography for the
      determination of the main fluorescent component of Ukrain, a novel antitumor and
      immune-stimulating drug. Our method was based on ion-pair separation of Ukrain
      from perchloric acid extracts using reversed-phase column, buffer with high
      molarity (0.5 M potassium phosphate, pH 2.65), high concentration of ion-pair
      reagent in the mobile phase (10 mM octylsulfonic acid), controlled temperature of
      the separation (45 degrees C) and detection by fluorescence (360/455 nm). Under
      the above conditions a peak of the main Ukrain compound was resolved from
      fluorescent peaks of the sum of alkaloids of Chelidonium majus L. although
      several peaks of alkaloids were retained in Ukrain as traces. The height of this
      main peak was nearly constant, while the alkaloid peaks varied depending on the
      series of the preparation; chelidonine and thio-triethylenephosphoramide gave no
      peaks. Analytical recovery for Ukrain from human plasma was 98.0 +/- 4.5%.
      Therefore, Ukrain possesses neither significant stable binding to plasma proteins
      nor adsorption in blood cells.

PMID- 11345024
TI  - The dynamics of concentration of the main fluorescent component of Ukrain in the
      tissues and blood plasma of rats with W-256 tumor after a single intravenous
      injection.
AB  - We determined the blood plasma and tissue concentrations of the main fluorescent
      component of free Ukrain after a single intravenous injection of this substance
      (0.25 mg/kg) to intact and carcinosarcoma W-256 bearing rats using ion-pair high
      performance liquid chromatography with fluorescent detection. The plasma and
      tissue concentrations of Ukrain were lower than expected, assuming its uniform
      tissue distribution and first-order kinetics. W-256 tumor tissue was the only
      tissue that showed accumulation of Ukrain (its concentration at 45 min after
      injection was up to 2.84-fold higher than in the blood plasma). Based on the
      elevation of Ukrain concentration in tissues at approximately 15 min after
      injection and taking into account its high molecular weight as well as the high
      dimensions of the Ukrain molecule or ion at physiological pH values, we conclude
      that the preparation penetrates into tissues by active transport or by favored
      diffusion. Due to the existence of such transport systems together with excretion
      of Ukrain and probably also its biotransformation, the disappearance of the
      preparation from the blood cannot be described using a one-compartment model. A
      relatively higher affinity for Ukrain was observed in tumor tissue and liver,
      while affinity was lowest in the brain and muscles. The presence of tumors
      decreased Ukrain concentrations in plasma and normal tissues in comparison with
      those in control animals.

PMID- 11345025
TI  - Ukrain (NSC-631570) in the treatment of pancreas cancer.
AB  - The aim of this study was to investigate the effects of Ukrain in the treatment
      of pancreatic cancer. Most patients with advanced pancreas cancer experience pain
      and have to limit their daily activities because of tumor-related symptoms.
      Currently, there is no satisfactory treatment for pancreas cancer. The 12-month
      survival rate is approximately 18% for patients treated with gemcitabine and only
      around 2% for those treated with 5-fluorouracil. Between January 1, 1996 and
      December 31, 1999 42 patients with advanced symptomatic pancreas cancer were
      randomly assigned to receive either vitamin C (5.4 g every second day, repeated
      10 times) and Ukrain (10 mg every second day, repeated 10 times) (21 patients),
      or vitamin C (5.4 g every second day x 10) and normal saline (10 ml) (control
      group, 21 patients). The primary measure of efficacy was overall survival. Other
      evaluation criteria included change in body weight, pain intensity (measured by
      analgesic consumption) and Kamofsky performance status. The one-year survival was
      81% in the Ukrain group compared with 14% in the control group. The 2-year
      survival was 43% in the Ukrain group compared with 5% in the control group. In a
      recent study of 126 patients treated with gemcitabine or 5-fluorouracil, none of
      the patients survived beyond 19 months. The longest survival in the Ukrain group
      was 54 months after the start of therapy (from March 1996 to date). The last
      follow-up of other patients was on September 6, 2000. Median survival was 17.17
      months for Ukrain-treated patients and 6.97 months for the control group and mean
      survival was 21.86 and 8.92 months for the Ukrain and control groups,
      respectively (p = 0.001). Ukrain treatment was well tolerated. We conclude that
      Ukrain prolongs survival of pancreas cancer patients. To determine whether and to
      what extent this drug can be used as standard therapy in pancreas cancer, a phase
      III study should be carried out.

PMID- 11345026
TI  - Results of Ukrain monotherapy of prostate cancer.
AB  - This study included 15 patients with newly diagnosed prostate cancer with an
      average age of 71 years (62-85 years). The patients received Ukrain at a total
      dose of 100 mg (10 mg intravenously every second day, 10 injections altogether).
      After two to three injections of Ukrain, all the patients noted considerable
      subjective improvements in their state. Ukrain increased the amount of total T
      lymphocytes, including "active" T-lymphocytes, decreased the content of T
      suppressors and increased that of T helpers, correspondingly raising the T
      helper/T-suppressor ratio. Our results undoubtedly indicate the efficacy of
      Ukrain in the treatment of prostate cancer.

PMID- 11345027
TI  - New biochemical mechanisms of the anticancer effect of Ukrain in the treatment of
      cancer of the urinary bladder.
AB  - The aim of this study was to elucidate the mechanisms of the anticancer effect of
      Ukrain by comparing the processes of formation of the pool of free amino acids
      and their derivatives in the blood plasma and tumor biopsy specimens and
      unchanged bladder tissue in 28 patients with T1N0M0 bladder cancer. The
      examination was carried out before and after Ukrain treatment (10 mg i.v./day,
      for 20 days), which was combined with systemic chemotherapy for bladder cancer.
      Twenty-eight patients served as controls and received systemic chemotherapy only.
      Compared with healthy donors, the blood plasma of patients with urinary bladder
      cancer showed decreased concentrations of thiol-containing free amino acids and
      glutamine (Gln) and increased levels of nonessential (glutamic acid, proline,
      alanine) and aromatic (phenylalanine) free amino acids. In contrast to
      conventional chemotherapy, treatment with Ukrain eliminated the blood plasma
      amino acid imbalance in patients with bladder cancer, concomitantly enriching the
      pool of free amino acids and their derivatives in unchanged urinary bladder
      tissue and decreasing concentrations of Gln and leucine (Leu), regulators of
      malignant cell proliferation and differentiation, by 30-50%. In this situation,
      the concentrations of Gln and Leu in tumor tissue and the surrounding healthy
      urinary bladder tissue correlated highly significantly and negatively (r = 
      0.95). In conclusion, Ukrain prevents active free amino acid transport into
      urinary bladder tumor tissue, inhibiting the activities of protein biosynthesis,
      gluconeogenesis and energy production. The combined decrease in Gln and Leu
      levels in urinary bladder tumor tissue is a specific sign of the antitumor effect
      of Ukrain and a mechanism of its cancerostatic action by controlling the
      processes of amino acid pool formation in the tumor.

PMID- 11345028
TI  - Comparison of the efficacy of different doses of Ukrain in the combined treatment
      of breast cancer.
AB  - The aim of this study was to compare the efficacy of different Ukrain doses in
      the combined treatment of 75 patients with breast cancer. The patients were
      divided into three groups: groups I and II (25 patients each) were treated with
      50 mg and 100 mg of Ukrain, respectively, before surgery; group III (25 patients)
      served as control (without Ukrain treatment). Clinical observations, biochemical,
      hormonal and immunologic indices indicated that both doses of Ukrain had a
      similar beneficial effect on patient outcome and may be indicated in the
      presurgical treatment of patients with breast cancer.

PMID- 11345029
TI  - Comparative evaluation of the efficiency of various Ukrain doses in the combined
      treatment of breast cancer. Report 1. Clinical aspects of Ukrain application.
AB  - This study was carried out in 75 patients with histologically confirmed breast
      cancer. Patients were divided into three groups of 25. The control group received
      symptomatic corrective therapy prior to mastectomy. The two other groups were
      given neoadjuvant therapy with Ukrain injections. The first group received a
      total course dose of 50 mg Ukrain at single doses of 5 mg injected every second
      day (a total of 10 injections) and the second group received a total Ukrain dose
      of 100 mg but with single doses of 10 mg. Five to seven days after the last
      injection patients from all groups were subjected to mastectomy according to
      Halsted, Patey or Madden. No allergic reactions or adverse effects were observed
      after the first course of injections or the whole course of Ukrain therapy,
      regardless of the dose. After five to six injections some patients noticed slight
      burning sensations and insignificant morbidity in the tumor area, which,
      according to a number of authors, testifies to the therapeutic activity of the
      preparation. Practically all patients who were administered Ukrain noticed
      remarkable positive changes in the second half of treatment: improvement in
      appetite, normalization of sleep, disappearance of general weakness and the
      appearance of confidence in recovery. After the course of treatment with Ukrain,
      the contours of the tumorous node became more clearly defined, which facilitated
      mastectomy. Changes in the tumor tissue were one-sided in their qualitative
      differences in comparison to the control group and were not dose-dependent.
      Qualitative and quantitative reactions to Ukrain by both intact lymphatic nodes
      and those affected by the metastatic process contribute to more quantitative and
      radical performance of the most important stage of mastectomy--removal of the
      regional cellulose together with the lymphatic nodes. The results of this study
      showed the efficiency of both doses (50 and 100 mg) of Ukrain with neither
      performing significantly better than the other.

PMID- 11345030
TI  - Comparative evaluation of blood plasma and tumor tissue amino acid pool in
      radiation or neoadjuvant preoperative therapies of breast cancer with the
      antitumor drug Ukrain.
AB  - This study comparatively evaluated free amino acid pool formation in patients
      with T1-3N0-2M0 breast cancer treated with the drug Ukrain (25 patients, i.v. 100
      mg/course) in combination with preoperative radiation or neoadjuvant therapies
      (25 subjects, total dose 20 Gy). All the patients underwent radical mastectomy.
      Preoperative radiation did not essentially change the range of the blood plasma
      parameters studied. However, we observed decreased concentrations of blood plasma
      ornithine and citrulline and a reduced content of aminobutyric acid, as compared
      with levels on admission, which may indicate an acceleration of detoxication
      processes in the liver. In comparison with healthy mammary gland tissue, the
      tumor tissue of the patients subjected to radiation therapy showed 1.5- to
      twofold increased concentrations of cysteate, taurine, aspartate, glutamate,
      proline, glycine, alanine, valine, tyrosine and histidine, which substantiates
      the idea of tumor tissue being a trap for numerous energy and plastic substrates
      and indicates active transport of the above compounds into the tumor. The
      application of Ukrain had virtually no influence on concentrations of the
      majority of blood plasma amino acids and derivatives: the total concentration of
      the compounds studied as well as the essential and nonessential amino acid pools
      remained unchanged. As compared with healthy breast tissue, the considerably
      increased levels of thiol-containing amino acids, such as methionine, cystine,
      cysteate and taurine, in the tumor tissue of patients receiving neoadjuvant
      therapy with Ukrain, indicates high activity of trans-sulfuration processes in
      this tissue. Simultaneously, in contrast to radiation therapy, Ukrain induced a
      marked dose-dependent increase in the concentration of proline in breast tumor
      tissue. The above changes were consistent with the results of the morphological
      study which confirmed the emergence of numerous foci of necrosis in the tumor and
      indicated activation of Ukrain-induced proteolytic and degradation processes in
      the tumor. The results obtained have led us to conclude that a mechanism of
      Ukrain's cancerostatic effect is to control the transport and reactions of
      intermediate amino acid metabolism as well as to activate proline biosynthesis in
      the tumor, causing enhanced development of connective tissue. It is suggested
      that an important practical conclusion from the present study is the lack of
      damaging effect of preoperative radiation therapy in the above regimen and the
      favorable (normalizing) action of Ukrain, at a course dose of 100 mg, on the
      amino acid pool formation in the organism of patients with breast cancer.

PMID- 11345031
TI  - Clinical aspects of cancer treatment and new biochemical mechanisms of the drug
      Ukrain.
AB  - A random group of 50 patients in tumor stages T1-3N0-2M0 was selected from breast
      cancer patients and given Ukrain therapy by intravenous injection. Twenty-five
      patients received a total dose of 50 mg Ukrain (5 mg every second day, 10
      injections altogether). Twenty-five patients received a total dose of 100 mg
      Ukrain (10 mg every second day, 10 injections altogether).

PMID- 11345032
TI  - Retrospective study of Ukrain treatment in 203 patients with advanced-stage
      tumors.
AB  - A total of 203 advanced-stage cancer patients suffering from different types of
      cancer who had exhausted all conventional forms of therapy were treated with the
      novel antitumor drug Ukrain over a period of 2.5 years at the Villa Medica Clinic
      in Germany. Seventy-six patients (37.4%) were simultaneously treated with
      regional deep hyperthermia in which tumor tissue was heated to > 42.5 degrees C.
      Patients also received complementary oncological treatment with selen,
      cimetidine, thyme extract and vitamin A. In view of the advanced stage of the
      disease, the results of therapy were surprising. Forty-one patients (20.2%)
      achieved total remission, 122 (60.1%) partial remission and only 40 (19.7%) did
      not respond to treatment. The highest response rates were in patients with
      seminoma (three out of four patients had total remission and one had partial
      remission) and in prostate cancer [14 out of 20 patients (70%) achieved total
      remissions and five achieved partial remission].

PMID- 11345033
TI  - Ukrain treatment in a patient with breast carcinoma. Case report.
AB  - A 50-year-old female patient with breast cancer (stage IV) was treated with
      Ukrain because of the impossibility of radiotherapy and chemotherapy. The first
      course led to a subjective improvement in her general condition, objective
      changes such as the appearance of border between the tumor and healthy tissues
      and a decrease in tumor size. Ukrain facilitated the surgeon in performing an
      operation to remove the primary tumor as well as the metastatic lymph nodes.
      After the second and third courses of Ukrain, the patient demonstrated clinical
      remission.

PMID- 11345034
TI  - Ukrain treatment of a patient with retroperitoneal synovial sarcoma. Case report.
AB  - A 23-year-old woman, diagnosed with a synovial sarcoma of the peritoneum,
      underwent an operation for tumor extraction. In the postoperative period, Ukrain
      was injected i.v. at a dose of 10 mg on alternate days, for a total of 10
      injections. After a 2-month break, this schedule was repeated. Ukrain treatment
      was well tolerated by the patient and there were no complications in the
      postoperative period. The following changes in immunohematological parameters
      were observed: increased total leucocytes, T lymphocytes and T helpers. Nearly 4
      years after Ukrain therapy, the patient is in complete remission.

PMID- 11345035
TI  - Ukrain treatment in a patient with metastatic renal cell carcinoma extending to
      the vena cava inferior. Case report.
AB  - A 52-year-old man with renal cell carcinoma was treated with surgery and
      chemotherapy (vinblastine). Ukrain was administered after tumor progression to
      the vena cava inferior and appearance of liver metastasis. The drug induced a
      complete remission, which has lasted 32 months since the first therapy course.

PMID- 11345036
TI  - Preliminary results of individual therapy of chronic hepatitis C by Ukrain and
      interferon-alpha.
AB  - The effects of Ukrain and recombinant human interferon-alpha 2b (IFN) on the
      state of the thiol-disulfide ratio (SH/SS) of the blood (Russian Federation
      patent no. 2150700) were studied in vitro using the amperometric titration
      method. The blood of 73 chronic hepatitis C (CHC) hepatitis C virus (HCV)-RNA
      positive patients was examined. Ukrain was tested in doses of 0.05-2.0
      micrograms/ml and IFN in 20-1000 U/ml of blood. After in vitro examination, 59
      patients were treated: 28 with Ukrain and 31 with IFN. The first group of 16
      patients (including eight with HCV genotype 1b) was treated with individually
      selected optimal doses of Ukrain (0.5-2.5 mg every second day). The second group
      of 12 patients was treated with doses of 2.5 mg Ukrain independent of in vitro
      test results. The third group of 31 patients was treated with individually
      selected optimal doses of IFN (0.5-2 MU 3 times a week). It was found that 79.4%
      of CHC patients were sensitive to Ukrain in vitro and 65.1% were sensitive to
      IFN. CHC patients with genotype 1b were sensitive to IFN only in 16.7% of cases
      while the figure for Ukrain was 92.3%. CHC patients with other HCV genotypes (3,
      1a, 2) were sensitive to Ukrain in 86.7% of cases and to IFN in 70.6%. After 1
      month of individual therapy with Ukrain, 87.5% of CHC patients, including six of
      eight cases with HCV genotype 1b, became PCR-HCV negative. In the group receiving
      the standard dose of Ukrain, virological response was only 33.3%. After 1 month,
      74.2% of CHC patients treated with individual doses of IFN became PCR-HCV
      negative and after 3 months 90.3% were PCR-HCV negative. The prognostic
      significance of the method for screening preparations for the treatment of CHC
      patients was 89.8%. Treatment with Ukrain was without serious negative effects
      and the number of side effects of IFN in individual therapy was significantly
      reduced. Ukrain can be used in the treatment of CHC patients, alone or in
      combination with IFN preparations; in the cases with HCV genotype 1b Ukrain seems
      more promising than IFN. Individual therapy with Ukrain and IFN increased the
      efficacy of treatment 2.5-fold in comparison with standard monotherapy with the
      same preparations, significantly decreased the number of side effects and
      dramatically improved cost-effectiveness.

PMID- 11345037
TI  - Effects of Ukrain on the activities of DNA-nicking enzymes.
AB  - We studied the effects of Ukrain, a novel antitumor drug, on the activities of
      calcium, magnesium-dependent endonuclease (CME) and manganese-dependent
      endonuclease (MnDE) in rat liver nuclei, the activity of topoisomerase I assessed
      by pUC19 plasmid relaxation and CME activity in the nuclei of lymphocytes from
      colon cancer patients. Ukrain was found to exert a dose-dependent inhibiting
      effect on both CME and MnDE, similar to that exerted by erythropoietin, which was
      used as a reference preparation. Both Ukrain and erythropoietin also caused dose
      dependent inhibition of topoisomerase I activity. The influence of Ukrain on CME
      activity in the nuclei of the lymphocytes of colon cancer patients was
      differential, depending on treatment efficacy. The results suggest that DNA
      nicking enzymes may be a target of Ukrain and may mediate its antitumor effects.

PMID- 11345038
TI  - Induction of apoptosis in cultured Chinese hamster ovary cells by Ukrain and its
      synergistic action with etoposide.
AB  - The induction of apoptosis by Ukrain, a novel antitumor drug, was studied in
      Chinese hamster ovary (CHO) cells bearing multiple copies of recombinant human
      erythropoietin gene incorporated into their genome (cell lines CHO-k38 and 
      k38/12). Ukrain was found to be capable of the in vitro induction of apoptosis in
      the cell lines studied. The effect was less expressed in cells with type I
      multiple drug resistance (k38/12). Ukrain acted synergistically with etoposide,
      i.e., the combined effect of both agents was evident at significantly reduced
      concentrations. This suggests that pharmacological compositions of the drugs may
      reduce the effective doses used in chemotherapy and thus significantly diminish
      its toxic side effects. Ukrain was found to exert an unusual effect, manifested
      as the inhibition of protein secretion by target cells. This phenomenon may be
      used for the express determination of cell sensitivity to colchicine-like
      cytostatics, including Ukrain.

PMID- 11345040
TI  - Cystatin C in LS lymphosarcoma and HA-1 hepatoma treated with Ukrain and
      cyclophosphamide and involvement of apoptosis.
AB  - The concentration of cystatin C, a cysteine proteinase inhibitor, was measured
      during the treatment of murine LS lymphosarcoma with cyclophosphamide and HA-1
      murine hepatoma with the antitumor drug Ukrain. It was shown that concentrations
      of cystatin C were very low in both the tumor tissues studied (HA-1 hepatoma
      cells and LS lymphosarcoma); increased cystatin C concentrations were found only
      in Ukrain-treated murine hepatoma, suggesting the mechanism of antitumor effect
      of this drug. Cyclophosphamide treatment in LS lymphosarcoma did not influence
      the concentration of cystatin C in tumor cells. At the same time, a marked
      increase in cathepsin B and cathepsin L activity in LS lymphosarcoma was found,
      indicating the involvement of apoptosis in the mechanism of antitumor action of
      cyclophosphamide. While the DNA from untreated LS lymphosarcoma was very
      homogenous and its molecular weight was high, the DNA from tumors of treated mice
      broke down, giving rise to the ladder figure characteristically produced by cells
      dying from apoptosis. Evidence was obtained that cyclophosphamide-induced tumor
      regression was effected by apoptosis.

PMID- 11345039
TI  - Chitotriosidase as a new marker of macrophage stimulation in a tumor model
      treated with cyclophosphamide and Ukrain.
AB  - Ukrain has previously been demonstrated to exert a malignotoxic effect in vivo.
      This antitumor drug has been effective in the treatment of some malignancies in
      experimental animals as a result of immunostimulation (macrophage stimulation).
      In the present study, serum chitotriosidase activity was measured as a
      biochemical marker of macrophage stimulation in several murine and rat models of
      macrophage stimulation. It was shown that zymosan, carboxymethylated glucan and
      Triton WR 1339 administration to CBA mice or Wistar rats was followed by a
      considerable increase in serum chitotriosidase activity. Murine LS lymphosarcoma
      development decreased serum chitotriosidase activity. Antitumor treatment by
      Ukrain or cyclophosphamide did not restore this index to the normal value.

PMID- 11345041
TI  - Influence of Ukrain and cyclophosphamide administration on HA-1 murine hepatoma
      and LS lymphoma on aspartic proteinase cathepsin D.
AB  - Cathepsin D, the major lysosomal aspartyl proteinase and a mediator of interferon
      gamma and tumor necrosis factor-alpha-induced apoptosis, was studied in murine
      models of LS lymphosarcoma treated by cyclophosphamide (possible apoptosis
      induction), and HA-1 hepatoma treated by Ukrain (positive antitumor effect). It
      was found that cyclophosphamide, as well as cyclophosphamide plus Ukrain,
      increased cathepsin D specific activity in mice with LS lymphosarcoma. Ukrain
      alone had no effect on cathepsin D activity in LS lymphosarcoma. In HA-1 hepatoma
      cells cathepsin D activity was not changed compared with intact normal murine
      liver (day 10) and activity decreased during tumor development (on day 12).
      Ukrain significantly increased cathepsin D activity in ascitic fluid (day 10) and
      had a tendency to increase cathepsin D activity in ascitic cells but not to the
      normal value.

PMID- 11345042
TI  - Cysteine proteinase inhibitor level in tumor and normal tissues in control and
      cured mice.
AB  - Cystatin C is the best known extracellular endogenous cysteine proteinase
      inhibitor and has been studied as a possible index of tumor growth and as a
      marker of the effectiveness of antitumor therapy. The aim of this study was to
      evaluate cystatin C concentrations in murine tumor tissues (compared with other
      organs not directly involved with tumor development, such as the liver and
      spleen) during treatment with several antitumor drugs (Ukrain and/or
      cyclophosphane). Cystatin C concentrations in murine tissues and biological
      fluids was determined by enzyme-linked immunosorbent (ELISA) assay. The cystatin
      C ELISA test is a sandwich immunoassay, which uses immobilized rabbit antihuman
      cystatin C Pab and mouse antihuman cystatin C Mab-HRP (monoclonal antibodies,
      conjugated with horseradish peroxidase). We observed decreased serum cystatin C
      concentrations compared with controls in all nontreated tumor models: HA-1
      hepatoma (solid and ascitic forms), lung adenocarcinoma (solid and ascitic forms)
      and LS lymphosarcoma. In the ascitic fluid of mice with HA-1 hepatoma the
      cystatin C concentration was much lower than in the serum of the same mice (about
      20-fold lower). In the HA-1 model of hepatoma cells cystatin C concentration
      decreased about 2-3-fold compared with the control (intact liver) and Ukrain
      significantly increased the cystatin C concentration. Cyclophosphane treatment of
      LS lymphosarcoma significantly increased the cystatin C concentration in serum.
      Cyclophosphane treatment (50 mg/kg, single injection) increased cystatin C by up
      to 8-fold more in tumor issue. Ukrain treatment of LS lymphosarcoma was also
      followed by increased levels of cystatin C in tumor tissue (4-fold);
      cyclophosphane plus Ukrain had a similar positive effect. In the group with LS
      lymphosarcoma Ukrain or cyclophosphane plus Ukrain treatment induced a
      significant increase in cystatin C concentration in liver. Liver cystatin C
      concentration decreased in the HA-1 hepatoma group and treatment with Ukrain or
      carboxymethylated beta-1, 3-glucan (CMG) increased this index in both groups.
      Spleen cystatin C concentrations decreased about 5-fold in LS lymphosarcoma
      compared with controls and combined treatment with cyclophosphane plus Ukrain
      restored the index to the normal value. We can conclude that both murine tumors
      studied were characterized by low cystatin C concentrations in tumor tissues and
      decreased cystatin C concentrations (to a lesser degree) were also observed in
      liver and spleen as a result of the "toxic" effect of tumor bearing. Effective
      treatment in all cases (especially with Ukrain or a combination of cyclophosphane
      plus Ukrain) induced a significant increase in cystatin C. Obviously, the
      decrease in cystatin C concentration predominantly in tumor tissue was connected
      with tumor development and restoration of cystatin C level may be used as a
      marker of efficacy of antitumor therapy.

PMID- 11345043
TI  - Influence of Ukrain on the nuclear thyroid hormone receptors after short-term
      gamma-irradiation.
AB  - The ability of Ukrain, a semi-synthetic alkaloid thiophosphoric acid derivative
      (NSC-631579), to influence thyroid hormone levels in plasma and nuclear thyroid
      hormone receptors in female rat liver, as well as to modify the effects of short
      term whole body gamma-irradiation on nuclear thyroid-hormone receptors in the
      liver was evaluated after intraperitoneal administration of the drug at 0.4 mg/kg
      body weight. Ukrain had no effect on the concentration of thyroid hormones in rat
      blood and increased the concentration of thyroid hormone receptors in the liver
      of intact rats during the first 2 months after administration. Ukrain normalized
      the level of nuclear thyroid hormone receptors influenced by short-term whole
      body gamma-irradiation of rats with 1 Gy, beginning from the first day after
      administration of the drug. Thus, Ukrain can minimize the consequences of
      irradiation in the endocrine system of experimental animals.

PMID- 11345044
TI  - Radiomodification effects of Ukrain, a cytostatic and immunomodulating drug, on
      intracellular glucocorticoid reception during short-term gamma-irradiation.
AB  - The ability of Ukrain, a cytostatic and immunomodulating semisynthetic compound
      of thiophosphate-modified alkaloids of Chelidonium majus L., to modify the
      effects of irradiation on intracellular glucocorticoid reception in female rat
      liver was evaluated after intraperitoneal administration of the drug at 0.4 mg/kg
      of body weight. Ukrain caused the normalization of the intracellular
      glucocorticoid-receptor system, influenced by short-term whole-body gamma
      irradiation of rats with 1 Gy, beginning on the 10th day after administration of
      the drug. It was found that Ukrain minimized the consequences of irradiation in
      the endocrine system of the experimental animals.

PMID- 11345045
TI  - Ukrain (NSC-631570) influences on bone status: a review.
AB  - Ukrain, a thiophosphoric acid alkaloid derivative of Chelidonium majus L., was
      shown to affect bone tissue metabolism as assessed in densitometric and
      biomechanical studies in rats. Its action could be slightly osteopenic at the
      highest doses administered to intact animals for a prolonged period of time. This
      phenomenon is possibly related to Ukrain's inhibitory effect on spontaneous
      locomotor activity of treated animals and/or to the stimulatory effect of the
      drug on the osteoclastic activity via the macrophage system. By far, the most
      important finding seems to be the anabolic effect of Ukrain on bone in
      ovariectomized rats, which is most probably related to induced increase in the
      production of gonadal hormones, predominantly estrogens. In this regard, the
      postmenopausal population of female patients treated for malignancies with Ukrain
      (and obviously the most numerous one) meritis clinical attention as far as the
      antiosteoporotic effects of this drug are concerned.

PMID- 11345046
TI  - Intermittent three-month treatment with Ukrain in intact and ovariectomized rats.
      Part I: Effect on selected biomechanical parameters of the femur.
AB  - Ukrain, an acid alkaloid derivative from Chelidonium majus L., was administered
      intraperitoneally to intact and ovariectomized sexually mature female rats at
      doses of 7, 14 and 28 mg/kg once daily for 10 days, followed by 10-day break.
      This procedure was repeated five times. At the end of this Ukrain treatment (24 h
      after the last dose of the drug), the right femora of the rats were harvested and
      a three-point bending test until shaft failure was performed under standard
      conditions. Assembled data, including ultimate strength, ultimate energy at
      failure and ultimate displacement, were assessed. Strength and energy were
      adjusted to accommodate differences between groups in the end body weight. These
      results showed a decrease in adjusted bone strength of ovariectomized rats as
      compared to sham-operated animals. None of the three long-term doses of Ukrain
      (i.e., 7 mg/kg, 14 mg/kg and 28 mg/kg) significantly altered the bone strength
      when it was adjusted to the end body weight of the ovariectomized animals. Intact
      rats that received a 28 mg/kg dose of Ukrain demonstrated decrease of bone
      strength of 13.5% when it was adjusted to the end body weight.

PMID- 11345047
TI  - Intermittent three-month treatment with Ukrain in intact and ovariectomized rats.
      Part II: Effect on bone mineral density of the femur.
AB  - Ukrain, an acid alkaloid derivative of Chelidonium majus L., was administered
      intraperitoneally to ovariectomized and control sexually mature female rats at
      doses of 7, 14 and 28 mg/kg once daily for 10 days, followed by 10-day break.
      This procedure was repeated five times. At the end of the Ukrain treatment (24 h
      after the last dose of the drug) the right femora of the rats were harvested and
      the bone densitometric parameters of the whole bone and distal metaphysial and
      intertrochanteric subregions were assessed using the dual energy x-ray
      absorptiometry densitometric method. The results showed no apparent decrease in
      bone mineral density in groups of rats studied. A nearly significant (p = 0.08)
      decrease of bone mineral content was observed in ovariectomized rats treated with
      14 mg/kg of Ukrain.

PMID- 11345049
TI  - Effect of Ukrain on human liver alcohol dehydrogenase activity in vitro.
AB  - In the present study it was found that Ukrain inhibits the ethanol oxidation
      process catalyzed by human alcohol dehydrogenase (ADH). Ukrain at a concentration
      of 10(-6), 2.5 x 10(-6), and 5.0 x 10(-6) M decreased liver ADH activity in the
      presence ethanol (approximately 8.41%, 13.28%, 16.69%, respectively) as well as
      in the presence of methanol (approximately 13.29%, 19.07% and 42.20%,
      respectively).

PMID- 11345048
TI  - Intermittent three-month treatment with Ukrain in intact and ovariectomized rats.
      Part III: Effect on the native electron paramagnetic resonance signal intensity
      of the femur.
AB  - Ukrain, an acid alkaloid derivative of Chelidonium majus L., was administered
      intraperitoneally to ovariectomized and sexually mature female control rats at
      doses of 7, 14 and 28 mg/kg once daily for 10 days, followed by a 10-day break.
      This procedure was repeated five times. At the end of the long-term treatment
      with Ukrain (24 h after the last dose of the drug) the left femora of the rats
      were harvested. Dried bones were studied by electron paramagnetic resonance (EPR)
      method. Significant changes in the intensity of the native signal were observed
      within the groups (ANOVA, p = 0.0001); the lowest value was observed in the
      ovariectomized rats treated with 28 mg/kg of Ukrain (decrease of 40.8% compared
      to the ovariectomized group, p = 0.005). A significant increase in the intensity
      of the signal was observed in the intact 7 mg/kg Ukrain-treated group (34.7%
      compared to controls, p = 0.004).

PMID- 11345051
TI  - Abstracts for the Paleoanthropology Society Meetings. Kansas City, Missouri, USA.
      27-28 March 2001.

PMID- 11345052
TI  - Spectrum of rolandic epilepsy: Agreements, disagreements and open questions.
      Proceedings of an international workshop. September 10, 1999, Kiel, Germany.

PMID- 11345050
TI  - Ukrain: a novel antitumor drug.
AB  - A review of the recent literature on the new anticancer drug Ukrain is provided
      herein. We review Ukrain, a thiophosphate derivative of alkaloids from
      Chelidonium majus L., its capacity to exert selective cytotoxic and cytostatic
      effects on tumor cells, simultaneously acting as an immune response modifier, its
      good tolerance and lack of side effects even after long-term application,
      perspectives of the application of this drug in oncology.

PMID- 11345053
TI  - Current literature in mass spectrometry.

PMID- 11345054
TI  - Recommendations for the use of inactivated influenza vaccines and other
      preventive measures.

PMID- 11345056
TI  - Animal Models of Peritoneal Dialysis. Proceedings of a symposium. Madrid, Spain,
      April 2000.

PMID- 11345055
TI  - Does the availability of a neuraminidase inhibitor impair influenza vaccination?
      A report from Austria.

PMID- 11345057
TI  - Laparsocopic ureteroureterostomy for retrocaval ureter.
AB  - Two cases of retrocaval ureter are reported that were successfully treated by a
      laparoscopic approach. Case 1 was a 20-year-old woman who presented with symptoms
      of a right ureter stone. Case 2 was a 23-year-old woman who had suffered from
      recurrent right flank pain with gross hematuria. A transperitoneal approach was
      used for case 1, and a retroperitoneal approach was used in case 2. Both were
      successfully treated with laparoscopic ureteroureterostomy using an
      intracorporeal suture technique. Laparoscopic surgery should be the first choice
      for retrocaval ureter not only because of the minimal invasiveness but also
      because of the cosmetic advantage compared to conventional open surgery. Further
      technical and instrumental advances are essential for intracorporeal suturing.

PMID- 11345058
TI  - Diversity among schistosomes: perspectives for control.

PMID- 11345059
TI  - A Giardia feast.

PMID- 11345060
TI  - Morbidity in schistosomiasis: an update.

PMID- 11345061
TI  - Letter to the editor: human herpesvirus 6 serologic responses.

PMID- 11345062
TI  - Vitamin and mineral nutrition for the health and development of the children of
      Europe.
AB  - Most European countries are now affected by demographic transition and changing
      epidemiology of disease; the nutrition of children is increasingly recognised as
      crucial for present and future health. Adequate dietary intake and nutritional
      status among children are important for their own growth, development and
      function but there is now increasing evidence that childhood nutrition also
      influences adult health. Intrauterine nutrition influences adult morbidity and
      mortality, but the childhood diet and nutritional status modify the increased
      risk of being born small. Thus, childhood diet needs to be taken more seriously
      in order to improve a nation's health as well as producing bright, active
      children. A key factor is the recognition that nutritional interventions at
      different stages of the life cycle are necessary if childhood nutrition is to
      improve. The mosaic pattern of the geography and social structure of communities
      in Europe produces 'poverty' and 'consumer' related nutrition patterns - often
      side by side. At one extreme, there is an urgent need to prevent obesity; while
      at the other extreme serious attention is required towards the prevention of
      deficiency disorders, mostly related to poverty and social exclusion. Few
      European governments take childhood nutrition at all seriously. This paper
      reviews a number of micronutrient issues and makes the case for the development
      of evidence-based policies and programmes for improving the nutrition of children
      in Europe.

PMID- 11345063
TI  - A 33-year-old man presented with progressive neck pain and a subjective sensation
      of neck instability. Diagnosis: type II dens fracture complicating ankylosing
      spondylitis.

PMID- 11345064
TI  - Haemoptysis with a normal chest radiograph.

PMID- 11345065
TI  - Reply to: projected requirements for radiation oncologists and trainees in
      Australia and New Zealand to 2007: reply.

PMID- 11345066
TI  - Radiotherapy utilisation: reply.

PMID- 11345067
TI  - Alan Fersht. 2001 Stein and Moore Award.

PMID- 11345068
TI  - Arthur Horwich. 2001 Hans Neurath Award.

PMID- 11345070
TI  - Long term care insurance coming for federal workers and military.

PMID- 11345069
TI  - Migration '99. Proceedings of the 7th International Conference on the Chemistry
      and Migration Behaviour of Actinides and Fission Products in the Geosphere. Lake
      Tahoe, Nevada, USA. September 26-October 1, 1999.

PMID- 11345071
TI  - Allergic contact dermatitis from betamethasone valerate in Japan.

PMID- 11345073
TI  - History of hand surgery in Korea.

PMID- 11345072
TI  - Inefficacy of buprrenorphine in rats.

PMID- 11345075
TI  - Working conditions and sickness absence: a complex relation.

PMID- 11345074
TI  - Echinococcus multilocularis in carnivores from the Klatovy district of the Czech
      Republic.
AB  - A unique human case of alveolar echinococcosis was described in 1979 from the
      Klatovy district of the Czech Republic. However, there were no previous
      epidemiological studies in this area focusing on detection of the source of
      infection--Echinococcus multilocularis adults producing eggs. During the period
      June 1997 to April 1999, 29 out of a total of 46 (63.3%) red foxes (Vulpes
      vulpes) in the Klatovy district and one of four foxes (25.0%) in the Pilsen South
      district were found to be infected with adult worms of E. multilocularis. No E.
      multilocularis adults were found in other animals from the Klatovy district (i.e.
      three specimens of Martes martes, two Martes foina, one Mustela erminea, two
      Meles meles and one Felis catus f. domestica). An examination of faecal samples
      from 55 dogs (Canis familiaris) from the Klatovy district resulted in the
      detection of E. multilocularis DNA in one (1.8%) sample. The present results
      support the possibility that human alveolar echinococcosis previously described
      in the Czech Republic had the character of an autochthonous infection. There are
      also indications of a potential risk of infection to humans.

PMID- 11345076
TI  - Injectable opiate maintenance in the United Kingdom: a view from the United
      States.

PMID- 11345077
TI  - Not "Is it treatment?" but "Does it work?".

PMID- 11345078
TI  - Injectable opiate treatment--feasible but for whom, how, and to what ends?

PMID- 11345080
TI  - EULAR recommendations for the management of knee osteoarthritis.

PMID- 11345081
TI  - Coffee consumption, RF, and the risk of RA.

PMID- 11345082
TI  - Polyarteritis nodosa complicated by thrombotic thrombocytopenic purpura.

PMID- 11345083
TI  - Placement of intra-articular injections verified by ultrasonography and injected
      air as contrast medium.

PMID- 11345084
TI  - HLA class II alleles and synovial fluid cytology in RA.

PMID- 11345085
TI  - Lessons from the Interdisciplinary Generalist Curriculum Project.

PMID- 11345086
TI  - Bioavailability of nutrients and other bioactive components from dietary
      supplements. Proceedings of a conference. January 5-6, 2000. Bethesda, Maryland,
      USA.

PMID- 11345087
TI  - Clonotypic B cells in the peripheral blood of patients with multiple myeloma.

PMID- 11345088
TI  - Dalteparin-induced alopecia in hemodialysis patients: reversal by regional
      citrate anticoagulation.

PMID- 11345089
TI  - Transient mixed hematopoietic chimerism in dogs given thymic irradiation before
      and pharmacologic immunosuppression after marrow transplantation.

PMID- 11345090
TI  - Induction of proliferation and augmented cytotoxicity of gammadelta T lymphocytes
      by bisphosphonate clodronate.

PMID- 11345091
TI  - [In case of hog cholera in pregnant swine: abortion or euthanasia?].

PMID- 11345092
TI  - Increasing threat of Gram-positive bacterial infections in the intensive care
      unit setting.
AB  - The effects of resistance are being noted on an increasing scale in the intensive
      care unit (ICU). Around the world, new epidemiologic patterns of ICU occurrence
      are being observed for Gram-positive multidrug-resistant organisms. Current
      problems include the appearance of insusceptibility to vancomycin and other
      glycopeptides in Staphylococcus aureus organisms that are virulent enough to
      cause infection in patients with normal host defenses. In addition, multidrug
      resistant organisms like methicillin-resistant S.aureus are spreading from
      healthcare to community settings, and community organisms like Streptococcus
      pneumoniae are spreading to healthcare settings. Focal persistence and subsequent
      worldwide spread of enterococci resistant to vancomycin and other glycopeptides
      and multiple-resistance mechanisms in the same organism also require attention.
      Strategies such as multidisciplinary management of infections, appropriate
      infection control measures, and surveillance of resistance patterns are necessary
      to address the problem of resistance. Intensivists have been prominent in
      research and control efforts in this field and should continue to lead future
      efforts.

PMID- 11345093
TI  - [Clinical study of dermoid cysts of the ovary. 1946].

PMID- 11345094
TI  - The interference threshold of cardiac pacemakers in electric 50 Hz fields.
AB  - The aim of the study was to determine a 'worst-case' and a 'real-case'
      interference threshold for implanted cardiac pace-makers (CPM) in electric 50 Hz
      fields as they appear in high-voltage plants, e.g. beneath high voltage overhead
      lines. For this purpose the resulting electrical potential distribution within
      the thorax area of volunteers from an external homogeneous electrical 50 Hz field
      was measured. Different factors such as different body geometries as well as
      inspiration and expiration of the lung were considered. Measurements showed that
      1 per 1 kV m(-1) unimpaired electrical field strength (RMS) an interference
      voltage of about 180 microVpp as real-case value an 400 microVpp as worst-case
      value would occur at the input of a unipolar ventricularly controlled, left
      pectorally implanted cardiac pacemaker. Therefore, it is possible under worst
      case conditions but unlikely under practice-relevant conditions that an implanted
      cardiac pacemaker is disturbed by present electric 50 Hz fields beneath high
      voltage overhead lines.

PMID- 11345095
TI  - Computerized breast thermography: study of image segmentation and temperature
      cyclic variations.
AB  - Breast cancer is a common and dreadful disease in women. The surface temperature
      and the vascularization pattern of the breast could indicate breast diseases.
      Establishing the surface isotherm pattern of the breast and the normal range of
      cyclic variations of temperature distribution can assist in identifying the
      abnormal infrared images of diseased breasts. This paper investigates the cyclic
      variation of temperature and vascularization of the normal breast thermograms
      under a controlled environment. More than 50 Asian women, were examined and some
      of them have been examined continuously for two month. All together, not less
      than 800 thermograms were obtained. Before these thermograms can be analysed
      objectively via a computer algorithm, they must be digitized and segmented. The
      authors present a method to segment thermograms and extract the useful region
      from the background. After the image processing, these thermograms can be
      analysed and then the best time to perform an examination can be chosen. All
      these results are important for establishing a data bank of normal breast
      thermography, to choose the best time for an examination and as a systematic
      methodology for evaluating and analysing the abnormal breast thermography in the
      future.

PMID- 11345096
TI  - Selection of pulse oximetry equipment for ambulatory monitoring.
AB  - PRIMARY OBJECTIVE: This communication describes the initial stage of a research
      project concerning the monitoring of SpO2 in infants prone to periods of
      spontaneous oxygen desaturation whilst freely moving around their home
      environment. The primary aim was to determine an appropriate probe type and site
      together with an assessment of the suitability of two commercially available
      oximeter units. RESEARCH DESIGN: The study comprised 19 comparative tests,
      totalling 162 hours of recordings at resolution one sample every four seconds.
      Comparisons are drawn between probes, probe sites and pulse oximeters. MAIN
      OUTCOMES/RESULTS: The bias and precision is presented with respect to the probe
      and measurement site. Also, correlation between the trial and reference
      recordings is considered. CONCLUSIONS: It is concluded that ambulatory recording
      of SpO2 in infants utilizing equipment suitable for home monitoring can produce
      diagnostic data equivalent to that of the Ohmeda 3700 biox, but that an
      indication of movement artefact may be required for confirmation of accuracy. It
      became apparent that 'wrap around' probes, used on the index finger or big toe
      are the most suitable.

PMID- 11345097
TI  - Axial reciprocation of rotating impeller: a new concept of antithrombogenecity in
      centrifugal pump.
AB  - For long-term application, rotary pumps have to solve the problems of bearing
      wear and thrombosis along the bearing. Most investigators choose the magnetic
      bearing to realize zero-friction and no contact between the rotor and stator; the
      former avoids the mechanical wear and the latter eliminates the possibility of
      thrombus formation. The authors have tried and found, however, that it is
      difficult to apply a magnetic bearing to the rotary pump without disturbing its
      simplicity, reliability and implantability, and have therefor developed a much
      simpler and much more creative approach to achieve the same results. Instead of
      using a sliding bearing, a rolling bearing has been devised for the pump, and its
      friction is about 1/15 of the sliding bearing. Furthermore, a wear-proof material
      of ultra-high-molecular weight polythene has been adopted to make the rollers,
      and its anti-wear property is 8 times better than metal. Thereby, the service
      life of the bearing has been prolonged to ten years according to the documents
      provided by the producer. In order to prevent the thrombus formation along the
      bearing, the impeller reciprocates axiallly as the impeller changes its rotating
      speed periodically to produce a pulsatile flow. The reciprocation is the result
      of the effects of a magnetic force between the motor rotor and stator, and a
      hydraulic force between the blood flow and the impeller. Similar to a piston
      pump, the oscillating impeller can make the blood flow in and out of the bearing,
      resulting in wash-out once a circle. This obviously helps to prevent thombosis
      along the bearing and in the pump. The endurance tests with saline of this novel
      pump demonstrated the durabililty of the device. It promises to be able to assist
      the circulation of patients permanently, and to be able to replace heart
      transplantation in the future.

PMID- 11345098
TI  - Optimization of the defibrillation current density in the heart region by a two
      layer segmented electrode.
AB  - Transthoracic defibrillation is a procedure applying high intensity electrical
      current through the thorax region by electrodes, in order to simultaneously
      activate most of the myocardial cells, thus enforcing them to reinstate a normal
      rhythm. A solution is proposed for analysis and synthesis of the current density
      distribution field in the heart region. In an attempt to reach uniform excitation
      of the greatest possible quantity of myocardial cells, a field image is searched
      for, with the J-vector uniformity distribution as a criterion. The finite element
      method and the method of approximating functions are used, as well as nonlinear
      programming. This approach resulted in designing a two-layer defibrillation
      electrode, with the layer applied to to the thorax divided in three different
      resistivity regions.

PMID- 11345099
TI  - Longitudinal variations of characteristic frequencies of skeletal muscle fibre
      potentials detected by a bipolar electrode or multi-electrode.
AB  - We aimed to reveal reasons for longitudinal variations of characteristic
      frequencies of electromyographic signals detected by surface longitudinal multi
      electrodes. Since the terminal phases were reduced in bipolar recordings, we
      tested whether the frequency variations reflected the effects of the excitation
      origin and extinction as in monopolar recordings. A precise and fast convolution
      method to calculate the signals detected by a multi electrode was suggested. The
      contribution of different electrode poles was introduced in the impulse response.
      When a longitudinal multi-electrode with an even number of poles was positioned
      above the end-plate of asymmetrical fibres, the signal mainly reflected the
      processes of the excitation extinction This increased the signal mean and median
      frequencies Although the effects of origin and extinction of the excitation were
      significantly reduced in the spatially filtered signals, the frequency variations
      along the fibre reflected these intrinsic features of any skeletal muscle fibre
      of finite length.

PMID- 11345100
TI  - State of the American Institute of Ultrasound in Medicine.

PMID- 11345101
TI  - Spiral computed tomographic imaging related to computerized ultrasonographic
      images of carotid plaque morphology and histology.
AB  - OBJECTIVE: Echolucency of carotid atherosclerotic plaques, as evaluated by
      computerized B-mode ultrasonographic images, has been associated with an
      increased incidence of brain infarcts on cerebral computed tomographic scans. We
      tested the hypotheses that characterization of carotid plaques on spiral computed
      tomographic images correlates with that on computerized B-mode ultrasonographic
      images and that spiral computed tomographic imaging predicts the
      histomorphometric plaque content. METHODS: The study included 38 patients with
      neurologic symptoms and at least 50% stenosis of the ipsilateral carotid artery.
      High-resolution B-mode ultrasonographic images and spiral computed tomographic
      images of carotid plaques were computer processed to yield a quantitative
      measure, the gray scale level of the plaque. RESULTS: The mean Hounsfield value
      for spiral computed tomographic images correlated with the gray scale median for
      B-mode ultrasonographic images (univariate linear regression analysis: r = 0.45;
      P = .01) and the histologic content of calcification in the plaque (r = 0.34; P =
      .04) but not with lipid, hemorrhage, or fibrous tissue in the plaque.
      CONCLUSIONS: Spiral computed tomographic imaging seems to correlate with B-mode
      ultrasonographic imaging for showing plaque characteristics. Spiral computed
      tomographic attenuation was also correlated with the amount of calcification
      noted on histologic examination but not with lipid and hemorrhage, the components
      thought to characterize vulnerable, rupture-prone plaques.

PMID- 11345102
TI  - Can the dimensions of artificial tendon lesions be predicted
      ultrasonographically? A cadaveric study.
AB  - OBJECTIVE: To prove the reliable assessment of artificial partial tendon lesions
      in cadavers. METHODS: The tendon of the tibialis anterior muscle was cut twice
      (transversely, not standardized depths) along its dorsal surface. The dimensions
      were measured by using a 10-MHz linear probe and a gliding caliper. The lesions
      were classified as type A tears (<60%; n = 15) and type B tears (>60%; n = 28).
      RESULTS: The depths of type A tears had high correlation (r = 0.827), and those
      of type B tears had low correlation (r = 0.415). This low correlation was due to
      subtotal lesions (50%-70%; r = 0.699). High-resolution ultrasonography allowed
      the correct detection of 14 type A tears and 21 type B tears (kappa = 0.63;
      accuracy, 81%; type B tears: sensitivity, 75%; specificity, 93%). CONCLUSIONS:
      High-resolution ultrasonography is able to assess the dimensions of artificial
      partial tendon lesions in cadavers and would be an accurate tool for determining
      the lesion percentages in patients with partial tendon tears.

PMID- 11345103
TI  - Ultrasonographic texture analysis of parenchymatous organs by the four
      neighborhood-pixels algorithm: clinical experiment.
AB  - OBJECTIVE: The parenchyma of organs such as liver, thyroid, and mammary gland
      during climacterium have common ultrasonographic textural features, which
      together form what we call small-dot-structure texture. To study this texture we
      designed the 4-neighborhood-pixels algorithm, an ultrasonographic texture
      analysis algorithm. The objective of this study was to confirm whether the 4
      neighborhood-pixels algorithm can reflect the features of small-dot-structure
      texture. METHODS: A changed small-dot-structure texture and 3 other textures were
      compared with the normal small-dot-structure texture in 4 groups, and a histogram
      algorithm was used for contrast with the 4-neighborhood-pixels algorithm.
      RESULTS: The 4-neighborhood-pixels algorithm could reflect all the textural
      differences, but the histogram algorithm could reflect only some of them.
      CONCLUSIONS: The 4-neighborhood-pixels algorithm is a good algorithm for
      analyzing ultrasonographic small-dot-structure texture. Not only can it reflect
      changes in the small-dot-structure texture, but it can also differentiate between
      small-dot-structure and non-small-dot-structure textures.

PMID- 11345104
TI  - Attenuation coefficient and sound speed in human myometrium and uterine fibroid
      tumors.
AB  - OBJECTIVE: To develop a noninvasive method for treatment of uterine fibroid
      tumors using high-intensity focused ultrasound. Optimal high-intensity focused
      ultrasound treatment would be dependent on quantitative information about
      ultrasonic tissue characteristics. METHODS: Ultrasonic attenuation and the sound
      speed of fresh human fibroid tumors and myometrium were measured as a function of
      frequency (1-3 MHz) by using a pulse transmission technique before and after in
      vitro high-intensity focused ultrasound treatment (3.5 MHz at an intensity of
      2,000 W/cm2). RESULTS: The ranges of the attenuation coefficients, before and
      after high-intensity focused ultrasound treatment, were 0.9 to 2.2 and 1.8 to 3.9
      dB/cm2, respectively, for fibroid tumors and 0.5 to 1.6 and 1.7 to 3.3 dB/cm2,
      respectively, for myometrium. Although the sound speed appeared to be independent
      of frequency (1,611 to 1,616 m/s at 1 to 3 MHz) in both types of tissues, a
      slight increase of approximately 4 to 14 m/s was observed after high-intensity
      focused ultrasound treatment. CONCLUSIONS: The results of this study represent
      our first reported values of the attenuation coefficient and sound speed in
      fibroid tumors and myometrium before and after high-intensity focused ultrasound
      treatment.

PMID- 11345105
TI  - State-of-the-art ultrasonography is as accurate as helical computed tomography
      and computed tomographic angiography for detecting unresectable periampullary
      cancer.
AB  - OBJECTIVE: To compare the ability of state-of-the-art ultrasonography with that
      of helical computed tomography and computed tomographic angiography in detecting
      unresectable periampullary cancer. In most patients periampullary cancer is
      unresectable because of either distant metastasis or local vascular involvement.
      The advent of gray scale and color Doppler ultrasonography has improved the
      ability of ultrasonography to detect vascular involvement. METHODS: Twenty-three
      consecutive patients with periampullary cancer were enrolled for prospective
      staging of their disease by comparing helical computed tomography and computed
      tomographic angiography with gray scale and color Doppler ultrasonography of the
      abdomen. Portal vein, superior mesenteric vein, splenic vein, and superior
      mesenteric artery involvement was graded 0 to 4, grade 0 being no vascular
      involvement and grade 4 being total occlusion of the vessel. Agreement between
      ultrasonography and computed tomographic angiography for determining vascular
      involvement was measured by chi2 analysis. RESULTS: Two patients (9%) were
      excluded because excessive overlying bowel gas hampered the ability of
      ultrasonography to visualize the pancreas. For the remaining 21 patients, there
      was significant agreement between ultrasonography and computed tomographic
      angiography for detecting vascular involvement in all vessels (P < .001; portal
      vein, kappa = 0.67; superior mesenteric vein, kappa = 0.67; splenic vein, kappa =
      0.85; and superior mesenteric artery, kappa = 0.59). Ultrasonography was in
      agreement with computed tomographic angiography in all cases of unresectability.
      Both modalities were equally poor in preoperatively showing lymphadenopathy and
      metastases. CONCLUSIONS: Provided that there is adequate visualization on
      ultrasonography of the head of the pancreas in the periampullary region, then
      state-of-the-art gray scale and color Doppler ultrasonography are as accurate as
      helical computed tomography and computed tomographic angiography for detecting
      the unresectability of periampullary cancer. If performed as the initial
      investigation and the region of the pancreatic head is clearly shown, and if
      vascular encasement or occlusion or distant metastasis is identified, further
      investigations are unnecessary.

PMID- 11345106
TI  - Gray scale sonography of breast masses in adolescent girls.
AB  - OBJECTIVE: To assess the sonographic findings of breast masses in adolescents and
      the usefulness of sonographic patterns for suggesting a specific diagnosis.
      METHODS: The sonograms and medical records of 57 girls (mean age, 15.4 years)
      with palpable breast masses were retrospectively reviewed. Three observers
      reviewed the sonograms for multiple sonographic findings. Surgery or clinical
      findings established diagnoses. Statistical analysis was done to determine how
      well sonographic findings alone and in combination agreed with final histologic
      diagnoses. RESULTS: Diagnoses included cysts (n = 12), abscesses (n = 7),
      fibroadenomas (n = 36), a lactating adenoma (n = 1), and a phyllodes tumor (n =
      1). The sonographic findings varied significantly among lesion types (P < or =
      .005). CONCLUSIONS: Our experience suggests that virtually all breast masses in a
      pediatric population are benign and that sonography has the ability to
      differentiate among cystic, inflammatory, and solid masses.

PMID- 11345107
TI  - High detection rate of breast ductal carcinoma in situ calcifications on
      mammographically directed high-resolution sonography.
AB  - OBJECTIVE: To assess the high-frequency sonographic characteristics of ductal
      carcinoma in situ of the breast. METHODS: In a retrospective review, we
      identified 18 patients with biopsy-proven pure ductal carcinoma in situ who had
      received mammographic and high-frequency sonographic examinations at transducer
      frequencies of 8-15 MHz, 8-5 MHz and 5 to 13 MHz [corrected]. RESULTS: All 18
      patients had mammographically identified calcifications. Four (22%) of the 18 had
      either asymmetric focal mammographically identified densities or masses with the
      calcifications. These calcifications were identified sonographically in 17 (94%)
      of the 18 patients. In 9 (50%) of 18 patients, the calcifications were associated
      with sonographically detected malignant masses, and in 3 (17%) of 18 patients the
      calcifications were within focally dilated ducts. Lesions that had masses or
      dilated ducts visible on sonography represented 9 (82%) of 11 of the grade 3
      neoplasms and only 2 (28%) of 7 of the grade 1 and 2 tumors. This difference was
      statistically significant (P < .039). CONCLUSIONS: Our study showed that ductal
      carcinoma in situ may appear on sonography as calcifications, masses, or focally
      dilated ducts. Those lesions that were associated with masses or dilated ducts on
      sonography were more likely high-grade histologic specimens.

PMID- 11345109
TI  - The role of contrast-enhanced sonography for radiofrequency ablation of liver
      tumors.
AB  - OBJECTIVE: To assess the feasibility and usefulness of contrast-enhanced
      sonography for tumor detection and guidance of liver VX2 tumor ablation and to
      evaluate post radiofrequency ablation effectiveness. METHODS: VX2 tumors were
      implanted into the livers of 6 rabbits. Both conventional and harmonic gray scale
      and power Doppler imaging were performed with a commercially available scanner to
      evaluate the liver tumors before and after intravenous injection of a sonographic
      contrast agent before and after radiofrequency ablation. Contrast-enhanced
      imaging was used to detect the tumors before ablation, to guide needle insertion,
      and to measure the ablation sites after radiofrequency ablation. Pathologic
      examination was performed for comparison. RESULTS: Three tumors were seen without
      contrast enhancement, whereas 10 tumors (<1 cm) were detected with contrast
      enhancement. Intentionally, 2 tumors were completely ablated and 5 tumors were
      partially ablated. In 3 cases, incompletely ablated tumors could only be
      identified on contrast-enhanced Doppler imaging by enhancing the detection of
      residual tumor vascularity. There was excellent concordance between sonographic
      imaging and gross pathologic findings. CONCLUSIONS: Contrast-enhanced sonographic
      imaging appears useful for detection of liver tumors and for guiding and
      monitoring tumor ablation therapies.

PMID- 11345108
TI  - Detection of liver metastases: comparison of contrast-enhanced wide-band harmonic
      imaging with conventional ultrasonography.
AB  - OBJECTIVE: To compare the detection rate of conventional ultrasonography and
      contrast-enhanced wide-band harmonic ultrasonographic imaging in the detection of
      small liver metastases. METHODS: Consecutive patients with histologically proved
      gastrointestinal carcinoma liver metastases were studied. Biphasic helical
      computed tomography, conventional ultrasonography, and contrast-enhanced wide
      band harmonic imaging were performed on all patients within a 5-day period. The
      biphasic helical computed tomographic scans were reviewed and interpreted by a
      skilled radiologist. The number of lesions and their descriptive characteristics
      were recorded for analysis. In addition, videotape recordings of the conventional
      ultrasonography and contrast-enhanced wide-band harmonic imaging were blindly
      reviewed, after which the number of detected lesions and their characteristics
      were then compared with those detected on biphasic helical computed tomography,
      considered the standard of reference. RESULTS: Twenty-eight patients (10 female
      and 18 male; age range, 45-72 years) were studied. Conventional ultrasonography
      detected 37 (59%) of all lesions visualized by biphasic helical computed
      tomography. The detection rate for contrast-enhanced wide-band harmonic imaging
      was significantly higher (61 [97%] of 63). In our series, two 10-mm lesions near
      the diaphragm were not visualized by wide-band harmonic imaging. CONCLUSIONS: The
      use of contrast-enhanced imaging techniques significantly improves the
      ultrasonographic detection of liver metastases. Our results achieved the
      sensitivity of biphasic helical computed tomography.

PMID- 11345110
TI  - Color/power Doppler sonographic differential diagnosis of superficial
      lymphadenopathy: metastasis, malignant lymphoma, and benign process.
AB  - OBJECTIVE: Differentiation of lymph nodes as metastasis, malignant lymphoma, and
      benign lesions by gray scale and color/power Doppler ultrasonography has been
      reported. In this study we sought to determine patterns of abnormal vascularity,
      the relationship between diagnostic criteria and node size, and which vessel in
      the node was best suited for Doppler spectral analysis. Extrahilar vessels,
      defined as vessels entering through the lymphatic surface and not through the
      hilus, were also investigated. METHODS: One hundred twenty-nine nodes were
      examined by color/power Doppler ultrasonography. RESULTS: Extrahilar vessels were
      seen in 85.4% of metastatic, 40.5% of lymphomatous, and 7.7% of benign nodes
      regardless of node size. The mean pulsatility index and resistive index values of
      metastatic nodes were higher than those of benign nodes regardless of their size.
      Those of lymphoma were intermediate compared with the others. CONCLUSIONS: A
      pulsatility index greater then 1.3 and a resistive index greater than 0.72
      suggested malignancy as measured from any vessel.

PMID- 11345111
TI  - Ultrasonographic differentiation between tuberculous lymphadenitis and malignant
      lymph nodes.
AB  - OBJECTIVE: To assess the usefulness of ultrasonography in the differential
      diagnosis of cervical tuberculous lymphadenitis versus malignant lymph nodes.
      METHODS: Ultrasonography of cervical lymph nodes was performed with a real-time
      linear scanner using a 7.5- or 11-MHz probe or both. Ultrasonographic findings
      were retrospectively reviewed in 73 patients: 49 with malignant lymphoma, 15 with
      tuberculous lymphadenitis, and 9 with metastatic lymph nodes. RESULTS:
      Ultrasonographic features specific to cervical tuberculous lymphadenitis were
      strong echoes (33.3%) and an echogenic thin layer (86.7%). When the lymph nodes
      had at least 1 of these 2 features, tuberculous lymphadenitis was diagnosed with
      a sensitivity of 100% and a specificity of 100%. CONCLUSIONS: Ultrasonographic
      evaluation of cervical lymph nodes can be useful in the diagnosis of cervical
      tuberculous lymphadenitis.

PMID- 11345112
TI  - Flash echo gray scale imaging with subtraction in assessment of small
      hepatocellular carcinoma treated with percutaneous ethanol injection: preliminary
      report.
AB  - OBJECTIVE: To assess the therapeutic effect of percutaneous ethanol injection on
      small hepatocellular carcinoma by using a flash echo imaging system, a newly
      developed technique for detecting echoes from microbubble contrast agents more
      efficiently. METHODS: Six patients with 7 small nodular hepatocellular
      carcinomas, proved by fine-needle aspiration cytologic or pathologic examination,
      were included. Percutaneous ethanol injection was performed until there was no
      intratumoral color signal on conventional color and power Doppler
      ultrasonography. A bubble contrast agent was then injected, and flash echo
      imaging in the subtraction mode was performed for assessment of the therapeutic
      effect. Dynamic computed tomography, magnetic resonance imaging, and hepatic
      angiography were also used for evaluation of the therapeutic effect. RESULTS:
      Five tumors had perfusion defects that were equal in size to or larger than the
      tumors. No tumor stain was shown on hepatic angiography. Two tumors had partial
      perfusion defects. Viable tumors were confirmed by tumor resection in 1 case and
      cytologic examination in the other. CONCLUSIONS: Our preliminary results show
      that flash echo imaging with subtraction has potential value in evaluation of the
      therapeutic effect of percutaneous ethanol injection on small hepatocellular
      carcinoma.

PMID- 11345113
TI  - Identification of hepatic venous territories in liver resection by using color
      Doppler ultrasonography: report of two cases.
AB  - OBJECTIVE: Resection of the hepatic vein because of the proximity of tumors may
      result in increased congestion in the noncancerous parenchyma, which in turn may
      lead to functional hepatic volume loss and postoperative hepatic failure,
      especially in a case of low hepatic reserve. However, to our knowledge, no
      technique for estimating the extent of dependent hepatic venous territories
      before hepatic resection has been established. We examined the possibility of
      using color Doppler ultrasonography for this purpose. METHODS: A color Doppler
      system and a linear array transducer equipped with multiple Doppler frequencies
      ranging from 7 to 13 MHz were used intraoperatively. Two patients with
      hepatocellular carcinomas were examined. By tracking entire branches of the
      targeted vessel, from the trunk to the terminal branches extending to the liver
      surface, it was possible for the boundaries of the dependent areas to be
      projected and marked on the liver surface with either ink or electrocautery.
      RESULTS: In both cases, this method was effective for either minimizing the
      congestive area or preserving the hepatic mass that was being drained via
      aberrant routes. CONCLUSIONS: Identification of hepatic venous territories by
      means of color Doppler ultrasonography may provide new information about
      intrahepatic blood circulation and may increase the safety and curability of
      hepatic resection.

PMID- 11345114
TI  - Use of ultrasonographic demonstration of hepatic venous flow to aid decisions on
      venous reconstruction during hepatectomy in a patient with an inferior right
      hepatic vein.

PMID- 11345115
TI  - Penile leiomyosarcoma: sonographic and magnetic resonance imaging findings.

PMID- 11345116
TI  - Donor-derived malignancy: transmission of small-cell lung cancer via renal
      transplantation.

PMID- 11345117
TI  - Subcutaneous bronchogenic cyst: unusual unltrasonographic findings.

PMID- 11345118
TI  - Evidence for a direct projection from the postrhinal cortex to the subiculum in
      the rat.
AB  - Behavioral data indicate that three of the areas which form the parahippocampal
      region in the rat, i.e., the entorhinal, perirhinal, and postrhinal cortices,
      have different, although related functions that also differ from those of the
      hippocampal formation. These functional differences might be related to
      differences in connectivity, on the one hand with parts of the association
      cortex, and on the other with the hippocampal formation. In a previous study, we
      showed the existence of both a direct and an indirect projection from the
      perirhinal cortex to areas CA1 and subiculum of the hippocampus. Here we present
      the result of a second study, demonstrating a similarly organized projection from
      the postrhinal cortex to the subiculum, comprising both a direct and an indirect
      route. Electrical stimulation of the postrhinal cortex in vivo evoked field
      potentials throughout the subiculum and the dentate gyrus. Current source density
      analysis in both the subiculum and dentate gyrus revealed the presence of sink
      source pairs, indicative of a synaptic termination. Based on comparison with the
      sink-source pairs found after stimulation of the medial entorhinal cortex, we
      conclude that the connection between the postrhinal cortex and the dentate gyrus
      most likely is formed by a polysynaptic pathway mediated via the medial
      entorhinal cortex, while the pathway from the postrhinal cortex to the subiculum
      is likely monosynaptic. In order to substantiate these findings, we carried out
      several tracer experiments. Anterograde tracer injections in the postrhinal
      cortex resulted in labeled fibers in limited parts of the subiculum, but no
      anatomical evidence for a projection of the postrhinal cortex to the dentate
      gyrus was found. Additional retrograde tracer injections in the subiculum also
      showed evidence for a direct postrhinal-to-subiculum projection with a strong
      topological organization. Based on these combined anatomical and
      electrophysiological data, we conclude that the postrhinal cortex indeed can
      reach the subiculum via both a direct and an indirect pathway.

PMID- 11345119
TI  - Spatial and temporal patterns of morphogenesis of hippocampal pyramidal cells:
      study in the early postnatal rat.
AB  - Several studies have dealt with the morphogenesis of the rat hippocampal
      pyramidal cell, but little is known about how the different pyramidal cell shapes
      of CA fields differentiate from neuroepithelial cells, or about how the field
      morphological identity emerges. From our studies of pyramidal cell shapes in the
      CA1, CA3, and CA4 fields of hippocampi at postnatal developmental stages between
      P0 and P12, using fresh semidissociated slices and acutely dissociated cells, we
      identified the sequence of cell shape transformation by which they differentiate
      from simple bipolar to complex shapes characteristic of adult pyramidal cells of
      CA1 and CA3. Pyramidal cell morphogenesis does not occur synchronously throughout
      the CA hippocampus fields, but cells in the CA4 field undergo morphological
      differentiation at earlier stages, prenatally, than CA3 cells, and these in turn
      earlier than CA1 cells. Thus, during the P1-P6 stages, a gradient of shapes from
      less to greater differentiation was clearly observed from CA1 to CA4 in a single
      slice. Furthermore, a mixture of cells at different degrees of differentiation is
      observed in CA1 from P1 to P10, and in CA3 from P1 to P5. A gradient of shapes
      from more to less differentiation was observed at stages P5-P6 from septal to
      temporal. We describe two processes in the pyramidal cell morphogenesis in the
      CA1 and CA3 fields, the approximation to the soma of the point of bifurcation of
      the main apical process, and the acquisition of triangular shape of the soma,
      showing by a quantitative study of both processes that they occur earlier in CA3
      than in CA1. Our study, therefore, provides new insight into rat pyramidal cell
      morphogenesis, and indicates that this process might be differently regulated in
      the various CA fields. Hippocampus

PMID- 11345120
TI  - Differential mechanisms of Ca2+ responses in glial cells evoked by exogenous and
      endogenous glutamate in rat hippocampus.
AB  - The mechanisms of Ca2+ responses evoked in hippocampal glial cells in situ, by
      local application of glutamate and by synaptic activation, were studied in slices
      from juvenile rats using the membrane permeant fluorescent Ca2+ indicator fluo
      3AM and confocal microscopy. Ca2+ responses induced by local application of
      glutamate were unaffected by the sodium channel blocker tetrodotoxin and were
      therefore due to direct actions on glial cells. Glutamate-evoked responses were
      significantly reduced by the L-type Ca2+ channel blocker nimodipine, the group
      I/II metabotropic glutamate receptor antagonist (S)-alpha-methyl-4
      carboxyphenylglycine (MCPG), and the N-methyl-D-aspartate (NMDA) receptor
      antagonist (+/-)2-amino-5-phosphonopentanoic acid (APV). However, glutamate
      induced Ca2+ responses were not significantly reduced by the non-NMDA receptor
      antagonist 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX). These results indicate
      that local application of glutamate increases intracellular Ca2+ levels in glial
      cells via the activation of L-type Ca2+ channels, NMDA receptors, and
      metabotropic glutamate receptors. Brief (1 s) tetanization of Schaffer
      collaterals produced increases in intracellular Ca2+ levels in glial cells that
      were dependent on the frequency of stimulation (> or =50 Hz) and on synaptic
      transmission (abolished by tetrodotoxin). These Ca2+ responses were also
      antagonized by the L-type Ca2+ channel blocker nimodipine and the metabotropic
      glutamate receptor antagonist MCPG. However, the non-NMDA receptor antagonist
      CNQX significantly reduced the Schaffer collateral-evoked Ca2+ responses, while
      the NMDA antagonist APV did not. Thus, these synaptically mediated Ca2+ responses
      in glial cells involve the activation of L-type Ca2+ channels, group I/II
      metabotropic glutamate receptors, and non-NMDA receptors. These findings indicate
      that increases in intracellular Ca2+ levels induced in glial cells by local
      glutamate application and by synaptic activity share similar mechanisms
      (activation of L-type Ca2+ channels and group I/II metabotropic glutamate
      receptors) but also have distinct components (NMDA vs. non-NMDA receptor
      activation, respectively). Therefore, neuron-glia interactions in rat hippocampus
      in situ involve multiple, complex Ca2+-mediated processes that may not be
      mimicked by local glutamate application.

PMID- 11345121
TI  - Temporospatial expression of HSP72 and c-JUN, and DNA fragmentation in goat
      hippocampus after global cerebral ischemia.
AB  - The role of gene induction (expression of HSP72 and c-JUN proteins) and delayed
      ischemic cell death (in situ labeling of DNA fragmentation) have been
      investigated in the goat hippocampus after transient global cerebral ischemia.
      The animals were subjected to 20-min ischemia (bilateral occlusion of the
      external carotid arteries plus bilateral jugular vein compression) and allowed to
      reperfuse for 2 h, and then 1, 3, and 7 days. Histological signs of cell loss
      were not found in the hippocampus at 2 h, 1 day, or 3 days of reperfusion.
      However, such an ischemic insult produced extensive, selective, and delayed
      degeneration in the hippocampus, as 68% of the neurons in CA1 had died at 7 days,
      but cell loss was not detected in CA3 and dentate gyrus fields. Concomitantly, a
      high percentage of TUNEL-positive CA1 neurons (60+/-9%, mean +/- SEM) was seen at
      7 days, but not at the earlier time points. Mild induction of HSP72 was detected
      in the goat hippocampus after ischemia. The maximum percentage of HSP72-positive
      neurons (10-15%) was shown at 3 days of reperfusion and was concentrated mainly
      in the CA3 field, subiculum, and hilus, rather than in the CA1 field, whereas
      HSP72 expression was hardly detected at 7 days. At this later time point,
      scattered induction of nuclear c-JUN was found in a few neurons. The results show
      that: 1) postischemic delayed neuronal death selectively affects the CA1 field in
      the goat hippocampus, a phenomenon which seems to take longer to develop than in
      previously reported rodent models; and 2) postischemic expression of c-JUN does
      not appear to be related to cell death or survival, while the inability of most
      CA1 neurons to express HSP72 could contribute to neuronal death.

PMID- 11345122
TI  - Activation of the dentate gyrus by stimulation of the contralateral perforant
      pathway: evoked potentials and long-term potentiation after ipsi- and
      contralateral induction.
AB  - Rats were chronically implanted with stimulation electrodes in the perforant
      pathway (pp) bilaterally and a recording electrode in the dentate gyrus (DG)
      unilaterally. Evoked field potentials (EPs) were recorded upon alternating
      stimulation of the pp on both sides, and long-term potentiation (LTP) was
      induced. Besides the EP after ipsilateral stimulation, an EP with a latency of
      approximately 5.5-6.5 ms was also seen upon stimulation of the contralateral pp.
      This potential was reversibly abolished during pentobarbital anesthesia and
      irreversibly after lesioning of the ipsilateral angular bundle. Paired-pulse
      facilitation and paired-pulse depression, depending on interstimulus interval and
      intensity, were also observed. Therefore, this long-latency potential could be
      characterized as polysynaptic and induced perhaps by transsynaptic activation via
      the ipsilateral entorhinal cortex. Ipsilateral tetanization induced strong E/S
      potentiation of both the ipsilaterally and contralaterally evoked EP, but with
      different time courses. Tetanization of the contralateral pp did not induce LTP
      of the ipsilaterally induced EP in the first 4 h. But afterwards a late and
      slowly developing potentiation occurred. The contralaterally induced EP also
      showed potentiation of the population spike, which was not immediately detectable
      but developed slowly over time. The results can be interpreted such that, after
      stimulation of the pp, the DG on the opposite side cannot only be activated via
      the weak crossed entorhinal projection but also transsynaptically via an
      entorhino/entorhinal connection.

PMID- 11345123
TI  - PKC activation rescues LTP from NMDA receptor blockade.
AB  - It has been proposed that a critical step in long-term potentiation (LTP)
      expression is the activation of presynaptic protein kinase C (PKC) after
      activation of postsynaptic NMDA receptors. A prediction from this "synaptic
      dialogue" hypothesis (Routtenberg, Trends Neurosci 1999;22:255-256) is that the
      well-known blockade of LTP by NMDA receptor antagonists would be rescued by
      direct activation of PKC. To test this prediction we recorded extracellular EPSPs
      in the molecular layer of the dentate gyrus (DG) in the intact, anesthetized
      mouse after stimulation of the perforant path. Three experimental series were
      performed in which tetanization was applied after continuous infusion of 1)
      vehicle, 2) NMDA receptor antagonist dl-2-amino-5-phosphonovaleric acid (APV)
      (2.5+/-1.0 nmol), or 3) both APV and then PKC activator 4-beta-phorbol-12,13
      dibutyrate (PDBu, 9.0+/-1.0 pmol). LTP was reliably induced in the first series
      (124+/-5%, N = 6; 2.5 h after the tetanus), suppressed by APV in the second
      series (95+/-18%, N = 4), and restored in the third series (121+/-13%, N = 5).
      Decreased paired-pulse facilitation, an index of presynaptic involvement in LTP
      expression, was observed after tetanization in the first and third series, but
      not in the second series. Blockade of LTP by NMDA receptor antagonists that can
      be overridden by presynaptic activation of PKC is thus consistent with the
      proposed hypothesis. As LTP is rescued after NMDA receptor blockade in transgenic
      mice overexpressing growth-associated presynaptic protein GAP-43, we suppose that
      this protein is one of the presynaptic targets of PKC activation.

PMID- 11345124
TI  - Rats with lesions of the hippocampus are impaired on the delayed nonmatching-to
      sample task.
AB  - Rats with ibotenic acid lesions of the hippocampus (H-IBO) were trained on the
      trial-unique delayed nonmatching-to-sample task (DNMS) using a short delay of 4
      s. The H-IBO group learned the nonmatching rule as quickly as control animals.
      However, performance was impaired on the DNMS task when the delay between the
      sample and choice phase was increased to 1 or 2 min. The use of 4-s delay (probe)
      trials indicated that the H-IBO animals retained the nonmatching-to-sample rule
      throughout testing. In a second experiment, using the same groups of rats,
      extended training at the 1-min delay did not ameliorate the deficit produced by H
      IBO lesions. The finding of impaired recognition memory in rats after hippocampal
      lesions is consistent with findings from humans and monkeys. Several
      methodological issues are considered that have complicated the interpretation of
      earlier studies of recognition memory in rats following hippocampal lesions. The
      capacity for recognition memory in humans, monkeys, and rodents is discussed as a
      straightforward example of hippocampus-dependent (declarative) memory.

PMID- 11345125
TI  - Dorsal/ventral hippocampus, fornix, and conditioned place preference.
AB  - Conditioned place preference (CPP) is a learning paradigm requiring formation of
      associations between reward and particular locations. White and McDonald (Behav
      Brain Res 1993;55:269-281) demonstrated that amygdala (AMG) lesions impair, while
      fornix (Fx) lesions enhance learning of this task. In the present experiments, we
      replicated the effects of AMG and Fx lesions, but we also found that complete
      hippocampal (HPC) lesions interfere with normal performance. Thus, the effects of
      Fx and HPC lesions on CPP are opposite. This is in contrast with spatial learning
      in the water maze. Because it has been demonstrated that damage of dorsal HPC
      interferes to a greater extent with spatial learning than damage of ventral HPC,
      we also tested animals with either dorsal or ventral HPC disruptions on CPP.
      Lesions limited to dorsal HPC were followed by impairment on this task. In
      contrast, lesions limited to ventral HPC resulted in enhanced learning. We argue
      that Fx and HPC lesions do not have interchangeable effects in all learning
      paradigms. To explain the complex pattern of results presently obtained, we
      propose a novel hypothesis regarding behavioral functions of HPC neural circuits.
      Implications regarding the interaction between memory systems are also
      considered.

PMID- 11345126
TI  - Hippocampal diminution in PTSD: more (or less?) than meets the eye.

PMID- 11345127
TI  - Hypotheses and controversies related to effects of stress on the hippocampus: an
      argument for stress-induced damage to the hippocampus in patients with
      posttraumatic stress disorder.

PMID- 11345128
TI  - Are glucocortoids responsible for putative hippocampal damage in PTSD? How and
      when to decide.

PMID- 11345129
TI  - Atrophy of the hippocampus in posttraumatic stress disorder: how and when?

PMID- 11345130
TI  - Relationship between magnitude of damage to the hippocampus and impaired
      recognition memory in monkeys.
AB  - Two recent meta-analyses, drawing on data from many of the same studies with
      monkeys, reached different conclusions about the relationship between hippocampal
      damage and recognition memory performance. Both studies found evidence of
      recognition memory impairment following hippocampal damage. However, Zola et al.
      (J Neurosci 2000;20:451-463) found no significant correlation between extent of
      hippocampal damage and recognition memory performance, whereas Baxter and Murray
      (Hippocampus 2001;11:61-71) concluded that the extent of hippocampal damage in
      monkeys was inversely correlated with impaired performance. Here, we first
      consider the requirements for carrying out a valid meta-analysis, and point out
      that the analysis carried out by Baxter and Murray (Hippocampus 2001;11:61-71) is
      invalid on simple statistical grounds. We then adopt the appropriate statistical
      procedures (multiple regression analyses rather than simple correlational
      analysis) to assess the relationship between extent of hippocampal damage and
      recognition performance across different studies. None of these analyses,
      including a reanalysis of the data of Baxter and Murray (Hippocampus 2001;11:61
      71), revealed a significant inverse relationship between lesion size and
      behavioral impairment. Most of the variance was explained by differences between
      the studies that contributed to the meta-analysis, not by lesion size itself.
      Indeed, analysis of covariance indicated that there were differences among the
      studies beyond lesion size that significantly affected performance. Finally, we
      consider what relationship might hold between lesion size and memory performance
      in the monkey.

PMID- 11345131
TI  - Reciprocal connections between the entorhinal cortex and hippocampal fields CA1
      and the subiculum are in register with the projections from CA1 to the subiculum.
AB  - The topology of the connections between the entorhinal cortex (EC), area CA1, and
      the subiculum is characterized by selective and restricted origin and termination
      along the transverse or proximodistal axis of CA1 and the subiculum. In the
      present study, we analyzed whether neurons in CA1 and the subiculum that receive
      EC projections are interconnected and give rise to return projections to EC, such
      that they terminate deep in the area of origin of the EC-to-CA1/subiculum
      projections. Both for the lateral and medial subdivision of EC, the projections
      to CA1/subiculum, as well as the projections from CA1 to the subiculum and back
      to EC, are rather divergent. Interestingly, we only rarely observed evidence for
      the presence of "reentry loops," i.e., cells in layer III of EC giving rise to
      projections to interconnected neurons in CA1 and the subiculum, while the
      targeted CA1 neurons also projected back to the deep layers of the area of origin
      of the pathway in EC. We conclude that although fibers originating from a
      restricted part of EC distribute extensively in a divergent way along the
      longitudinal axis of CA1 and the subiculum, only restricted portions of the
      latter two areas, receiving inputs from the same entorhinal area, are
      interconnected. Moreover, only a small percentage of the CA1 neurons that project
      to the correspondingly innervated subicular neurons give rise to projections that
      return to the deep layers of the originating part of EC. The present findings are
      taken to indicate that the EC-hippocampal circuitry functionally comprises many
      parallel-organized specific "reentry loops."

PMID- 11345132
TI  - Real-time quantitative PCR of telomerase mRNA is useful for the differentiation
      of benign and malignant pancreatic disorders.
AB  - The presence of telomerase activity has been proposed as a specific and sensitive
      marker for malignant tissue, and positivity rates of up to 95% have been reported
      in pancreatic cancer. In the present study telomerase activity analysis was
      reevaluated in 29 pancreatic cancer tissues compared with 36 chronic pancreatitis
      tissues and 21 normal controls, and a study was made of whether malignant and
      benign pancreatic disorders can be better differentiated using a novel technique
      real-time quantitative PCR analysis-analyzing telomerase mRNA expression.
      Telomerase activity was present in 35% (10 of 29) of pancreatic cancer samples,
      3% (one of 36) of chronic pancreatitis samples, and none of the normal pancreatic
      tissue samples in the TRAP assay. Real-time quantitative PCR analysis revealed
      the presence of telomerase mRNA expression in 50% (10 of 20) of normal, 86% (31
      of 36) of chronic pancreatitis, and 90% (26 of 29) of pancreatic cancer samples.
      However, quantification of the expression data revealed that the relative
      increase above normal was 5.5 (range, 3.5-8.6) for chronic pancreatitis and 23.9
      (range, 18.6-30.7) for pancreatic cancer samples (p < 0.01). No relationship was
      found between telomerase activity and the fold increase of telomerase mRNA above
      normal and gender, patient age, tumor stage, or tumor grade. These data indicate
      that detection of telomerase activity using the TRAP assay has limitations in
      differentiating benign and malignant pancreatic disorders. However, telomerase
      mRNA analysis by real-time quantitative PCR analysis allows a highly sensitive
      detection and differentiation of pancreatic cancer from normal pancreas and
      chronic pancreatitis and thereby may serve as a new reliable, easy, and effective
      diagnostic tool for cancer diagnosis.

PMID- 11345133
TI  - Correlation between TGF-beta1 and p21 (WAF1/CIP1) expression and prognosis in
      resectable invasive ductal carcinoma of the pancreas.
AB  - Transforming growth factor-beta1 (TGF-beta1) inhibits the growth of a variety of
      epithelial cells; however, in many types of tumors it loses its inhibitory
      effect. p21(WAF1/CIP1), one of the cyclin-dependent kinase (Cdk) inhibitors
      induced by TGF-beta1, is considered a downstream effector of the growth
      inhibitory function of TGF-beta1. We assessed the clinicopathologic significance
      of TGF-beta1 and p21 expression in resectable invasive ductal carcinoma (IDC) of
      the pancreas. Immunohistochemical examination of the expression of TGF-beta1 and
      p21 in 62 patients revealed positive expression of TGF-beta1 in 28 (45%) and of
      p21 in 25 (40%) of the 62 patients, and a significant correlation between the two
      expressions. The survival curve of patients with TGF-beta1(+) tumors was
      significantly higher than that of patients with TGF-beta1(-) tumors; p21(+)
      patients showed a higher survival curve than did p21(-) patients, but the
      difference was not statistically significant. Simultaneous analysis of TGF-beta1
      and p21 expression showed that the patients with TGF-beta1(+)/p21(+) tumors had a
      significantly better prognosis than the others. Multivariate analysis showed that
      TGF-beta1 was a significantly low risk factor for death due to IDC. The
      concurrent evaluation of TGF-beta1 and p21 expression would be an effective tool
      in the prediction of the prognosis of patients with pancreatic cancer.

PMID- 11345134
TI  - A new peritoneal dissemination model established from the human pancreatic cancer
      cell line.
AB  - We established a new cell line, HPC-3P4a, with high peritoneal disseminated
      potential in nude mice. HPC-3P4a was derived from a human pancreatic carcinoma
      cell line (HPC-3) that had low capacity for peritoneal dissemination. HPC-3P4a
      developed peritoneal dissemination in 10 of 11 (90.9%) cases, whereas parental
      HPC-3 developed peritoneal dissemination in one of six (16.7%) cases. The
      metastatic foci in the peritoneum showed essentially the same histologic
      appearance of parental involvement. The tumorigenicity, motility, and adhesive
      activity of HPC-3P4a to the extracellular matrix were stronger than were those of
      the HPC-3. In FACS analysis, HPC-3P4a significantly increased the expression of
      alpha6 and alpha(v)beta5 integrins, while it decreased alpha2 integrin, hCD44H,
      and hCD44v 10, as compared with HPC-3. The VEGF production of HPC-3P4a was
      significantly lower than that of HPC-3. Analysis of gene macroarrays showed a
      variety of cytokines, interleukin, and other immunomodulatory, and their
      receptors were up-regulated and down-regulated on an mRNA level in HPC-3P4a
      cells, compared with HPC-3 cells. Intrasplenic injection of HPC-3P4a produced no
      liver metastasis. We named our original highly liver metastatic cell line HPC-3H4
      (previously reported). This HPC-3H4 cell was established by repeated intrasplenic
      injection from parental cell HPC-3; thus, it developed high liver metastasis.
      Moreover, HPC-3H4 developed peritoneal dissemination by intra-abdominal
      injection. In contrast, HPC-3P4a did not develop liver metastasis by intrasplenic
      injection. These findings are very interesting and might suggest that the process
      of hematogenous metastasis differed from that of peritoneal dissemination. Thus,
      this cell line may be useful for investigating the mechanism of peritoneal
      dissemination in human pancreatic cancer.

PMID- 11345135
TI  - CD95-related apoptotic machinery is functional in pancreatic cancer cells.
AB  - The CD95 (FAS, Apo-1) system is a major death pathway in normal and tumor cells.
      Recent evidence indicates that pancreatic cancer cells express CD95R and CD95L
      but are insensitive to CD95-mediated apoptosis. Here we show that treatment of
      human pancreatic cancer cells with RNA synthesis inhibitor actinomycin D (ActD)
      converted the phenotype of cancer cells from CD95 resistant to CD95 sensitive.
      Flow cytometric analysis demonstrated that all pancreatic cancer cell lines
      studied responded with cell surface CD95R and CD95L upregulation to bleomycin
      treatment, and PANC1 (mt p53) cells demonstrated a dose-dependent response to
      interferon gamma and bleomycin treatment with CD95R and CD95L up-regulation.
      However, only bleomycin sensitized PANC1 cells to CD95-mediated apoptosis. Taxol
      sensitized PANC1 and HPAC cells to CD95-mediated apoptosis without surface up
      regulation of CD95R. These data suggest that pancreatic cancer cells possess a
      p53-independent mechanism of CD95R and CD95L surface upregulation and that
      surface expression of CD95R is not predictive of apoptotic function. Protein
      extracts of HPAC and PANC1 cells treated for 24 hours with a combination of
      ActD/agonist anti-CD95 antibodies demonstrated significantly higher Acetyl-Asp
      Glu-Val-Asp-ase (DEVDase) cleavage activity (caspase 3-like activity) than
      extracts from cells treated with ActD only. In the present study, we also
      investigated the time kinetics of DEVDase (caspase 3-like) activation in PANC1
      (mt p53) and HPAC (wt p53) pancreatic cancer cell lines. We found that DEVDase
      activity in PANC1 cells responds to ActD and ActD/anti-CD95 antibodies earlier
      than in HPAC cells; however, at 24 hours HPAC cells demonstrated much stronger
      activation. Cytosolic protein extracts from untreated cells did not influence
      caspase 3-like activity when added to extracts from the ActD/anti-CD95 antibody
      treated cells. Collectively, these data suggest that pancreatic cancer cells have
      functional CD95-related apoptotic machinery with preserved apoptotic signal
      transduction, CD95R upregulation. and caspase activation. However, this system is
      blocked by some unknown protein(s) that is either located in the organelle
      fraction of the cell and/or requires an intact cell for manifestation of its
      activity.

PMID- 11345136
TI  - Growth rate of pancreatic adenocarcinoma: initial clinical experience.
AB  - A better understanding of the growth rate of pancreatic carcinoma is important in
      determining its natural course and in evaluating the effects of treatment or
      prognosis. The authors studied the growth rate of pancreatic carcinoma and the
      relation between its tumor volume doubling time (TVDT) and host survival. Nine
      patients with pancreatic carcinoma who underwent serial examinations by helical
      computed tomography but no anticancer treatment during the observation period
      were included. The TVDTs were calculated by measuring the tumor size on the
      helical computed tomograms. The mean TVDT of the nine primary lesions of
      pancreatic carcinoma was 159 +/- 67 days (median, 144 days), and the range was 64
      to 255 days. The correlation between TVDT and survival time was positive and
      significant (r = 0.793, p = 0.011). This preliminary study suggests that
      examination of TVDT may be useful in the clinical evaluation of prognosis for
      patients with pancreatic carcinoma in certain situations.

PMID- 11345137
TI  - Clinical management of intraductal papillary mucinous tumors of the pancreas
      based on imaging findings.
AB  - The aim of this study was to assess the imaging findings of pathologically proven
      intraductal papillary-mucinous tumors of the pancreas and the natural history of
      follow-up cases, and to optimize the therapeutic management of patients with
      these tumors according to their imaging findings. All nine patients with main
      duct type tumors were histologically diagnosed as having adenocarcinoma or
      adenoma, with no hyperplastic lesion. The images failed to discriminate between
      the two histologic types. In 26 patients with branch duct type tumors, all but
      one with intraductal mural nodules or tumors of > or = 30 mm had adenocarcinoma
      or adenoma, regardless of the caliber of the main duct. Of the nine patients with
      tumors < 30 mm and no mural nodules. three had adenoma, and six had hyperplasia.
      All of four patients had hyperplasia, with the additional caliber of the main
      duct being < 6 mm. In a series of 23 cases in which the patient was followed-up,
      no apparent progression was found in 17 patients who had no mural nodules and
      tumors of < 30 mm. Given these results, patients with main duct type tumors, and
      those with branch duct type tumors showing mural nodules or a tumor diameter of >
      or = 30 mm, are at high risk of developing neoplasms, including adenocarcinoma,
      for which surgical resection should be considered, whereas those patients with
      tumors < 30 mm and no mural nodules can be followed.

PMID- 11345138
TI  - Outcome of surgical treatment for chronic calcifying pancreatitis.
AB  - OBJECTIVE: To evaluate the short and long-term results of surgical treatment of
      calcifying chronic pancreatitis in our center. PATIENTS AND METHODS: We studied
      55 consecutive patients operated on for chronic calcifying pancreatitis during a
      period of 12 years. The mean follow-up period was 6.2 years. Main outcome
      measures were operative mortality and morbidity, degree of pain control, diabetes
      onset, survival, and causes of death. RESULTS: The etiology was alcoholic in 48
      patients and idiopathic in seven patients. A resection was performed in 78% of
      cases and a by-pass procedure was performed in 22%. Operative mortality was 3.6%;
      morbidity was 21.8%. A ductal adenocarcinoma was found in 3.6% of cases. The
      alcohol withdrawal rate was 78%. Complete pain control was achieved in 71.4% of
      the patients. Among diabetes, cirrhosis, type of surgery, smoking and alcohol
      abuse history, only alcohol withdrawal was associated with pain control (p <
      0.03). A late reintervention was needed in only one patient in the by-pass group.
      Five and 10-year survival rates for the entire population were 80% and 61%,
      respectively. Among alcohol, cirrhosis, diabetes, and type of surgery, only the
      former was associated with survival (p < 0.003). Five-year actuarial survival was
      55.6% for patients who continued drinking compared with 86.3% for ex-alcoholics.
      CONCLUSIONS: Surgical resection should be performed when required by the
      anatomical conditions because it was associated with good long-term pain control
      and low postoperative and late morbidity. Alcohol withdrawal has a key role for
      effective control of pain and prolonged survival.

PMID- 11345139
TI  - Overexpression of caspase-1 (interleukin-1beta converting enzyme) in chronic
      pancreatitis and its participation in apoptosis and proliferation.
AB  - Caspase-1, formerly designated interleukin-1beta converting enzyme, was the first
      described member of a group of cysteine proteases called caspases. It is
      suggested that caspases play an important role in apoptosis, but recent
      observations could show that caspase-1 might also be involved in cellular
      proliferation. We investigated the expression of caspase-1 in 38 chronic
      pancreatitis tissues, six pancreatitis tissues from patients with pancreatic
      carcinoma and nine normal pancreatic tissues by immunohistochemistry. Western
      blot analysis was used to confirm the immunohistochemical findings. We found a
      clear expression of caspase-1 in chronic pancreatitis, but not in normal
      pancreatic tissues. Interestingly, we found expression of caspase-1 in three
      distinct morphologic compartments: (i) in atrophic acinar cells (31 of 35; 89%),
      (ii) proliferating cells of ductal origin (33 of 38; 87%), and (iii) in acinar
      cells redifferentiating to form tubular structures (26 of 31; 83%). These
      immunohistochemical findings were confirmed by Western blot analysis, which
      showed an expression of caspase-1 in 85% of the tissues. No correlation was found
      between any of the examined clinicopathologic features and the caspase-1
      expression in chronic pancreatitis. In conclusion, the expression of caspase-1 is
      a frequent event in chronic pancreatitis and its distribution pattern may reflect
      two functions of this protease: on one hand its participation in the apoptotic
      pathway in atrophic acinar cells and, on the other hand, its role in
      proliferation and differentiation in proliferating duct cells.

PMID- 11345140
TI  - Increased expression of glutathione S-transferase-pi in the islets of patients
      with primary chronic pancreatitis but not secondary chronic pancreatitis.
AB  - The mechanism of tissue alteration in chronic pancreatitis (CP) is still unclear.
      Different hypotheses have been discussed, including increasing oxidant stress in
      the acinar cells, often as a result of exposure to xenobiotics. To evaluate the
      role of oxidative stress in CP, the authors investigated the expression of the
      drug-metabolizing phase II enzyme, glutathione S-transferase-pi (GST-pi), in the
      pancreatic tissue of patients with CP and compared it with the healthy pancreatic
      tissue from age-matched donors. Pancreatic tissue from patients with secondary CP
      resulting from ductal obstruction by pancreatic cancer (PC) was also examined.
      The percentage of cells immunoreacting with anti-GST-pi was counted within 15
      randomly selected islets in each slide of the three groups. In all specimens,
      ductal and ductular cells, and in PC, cancer cells, expressed GST-pi in a
      moderate intensity. Acinar cells did not stain. Various numbers of islet cells in
      each of the three groups were stained strongly. More islet cells expressed GST-pi
      in CP (42%) than in healthy pancreatic tissue (16%, p < 0.001) or PC (17%, p <
      0.001). Our results imply an important role of islet cells in the metabolism of
      substances, which are the substrate for GST-pi, and lend support to the
      hypothesis of oxidative stress as the cause of CP.

PMID- 11345141
TI  - Gastrointestinal, liver, and pancreatic involvement in adult patients with cystic
      fibrosis.
AB  - BACKGROUND: The clinical prevalence of cystic fibrosis (CF) in adults continues
      to rise, with a consequent impact on adult gastroenterology practice. AIM: To
      characterize the gastrointestinal manifestations of CF in adult patients.
      PATIENTS AND METHODS: The clinical records of 89 adult CF patients treated at our
      institution from 1992 to 1999 were reviewed. Patients were distributed into two
      groups: group A (39 patients), which consisted of patients who were diagnosed
      with CF at when they were younger than 14 years old and who survived into
      adulthood; and group B (50 patients), who were diagnosed with CF at the age of 14
      years or older. Data on CF genetic mutations, nutritional state, evidence of
      pulmonary, gastrointestinal, liver, or pancreatic involvement were collected for
      each patient. RESULTS: The most prevalent genetic mutation in our series was
      deltaF508, present in 50 patients (56.2%), 29 of whom belonged to group A and 21
      who belonged to group B. In group A, the deltaF508 mutation was associated with
      exocrine pancreatic insufficiency (PI) in 26 of 29 patients (89.6%), whereas in
      group B it was associated with PI in only four patients (19%). Overall, PI was
      present in 33 of 39 patients (84.6%) in group A and in eight of 50 patients (16%)
      in group B. Four patients in group B had experienced previous episodes of acute
      pancreatitis; two of them had associated PI. Of the 89 patients, 12 (10 in group
      A) were malnourished. Malnutrition was invariably associated with PI. Hepatic and
      biliary tree abnormalities were particularly prevalent in patients in group A and
      was usually associated with PI. Intestinal manifestations were uncommon.
      CONCLUSIONS: Diagnosis of CF before the age of 14 years is associated with
      greater gastrointestinal compromise than diagnosis at an older age, particularly
      with regard to PI. CF carriers of the deltaF508 mutation have an increased risk
      of developing gastrointestinal manifestations.

PMID- 11345142
TI  - Expression of tumor necrosis factor-alpha, interleukin-6, and interferon-gamma in
      spontaneous chronic pancreatitis in the WBN/Kob rat.
AB  - To clarify the pathophysiological significance of cytokines in chronic
      pancreatitis (CP), we analyzed tissue expressions of various cytokines in the
      onset and progression of spontaneous CP in the WBN/Kob rat. Four-week-old male
      WBN/Kob rats were fed a special pellet diet (MB-3) for 20 weeks, and 6 rats were
      killed every 4 weeks. Pathologically, CP occurred at 12 weeks and progressed
      thereafter. The inflammation and fibrosis peaked at 12 and 16 weeks,
      respectively. By semiquantitative reverse transcription-polymerase chain
      reaction, the expression of tumor necrosis factor (TNF)-alpha, interleukin (IL)
      6, and interferon (IFN)-gamma mRNAs peaked at 8, 12, and 16 weeks, respectively.
      Immunohistochemistry showed IL-6 expression in infiltrating inflammatory cells
      and vascular endothelial cells, whereas TNF-alpha was expressed in both acinar
      and infiltrating cells. IFN-gamma was localized to acinar, infiltrating and
      ductal cells, and its expression intensity showed significant correlation with
      those of fibrosis, type III collagen and alpha-smooth muscle actin. The in situ
      hybridization results were consistent with the RT-PCR data. These results suggest
      that tissue expressions of TNF-alpha and IL-6 are involved in the onset of
      pancreatitis and that IFN-gamma expression is related to the progression of CP.

PMID- 11345143
TI  - Ascites of rat experimental model of severe acute pancreatitis induces lung
      injury.
AB  - The molecular mechanisms that lead from acute pancreatitis (AP) to multiple organ
      failure remain to be clarified. We previously reported that ascitic fluids from a
      rat model of severe acute pancreatitis (pancreatitis-associated ascitic fluids,
      PAAF) transcriptionally activated endothelial cells and leukocytes in vitro. To
      clarify the role of ascitic fluids on the development of multiple organ failure
      in AP, we examined the effects of PAAF on the prognosis and immunohistologic
      findings in cerulein pancreatitis, an experimental model of mild pancreatitis in
      vivo. Intraperitoneal injection of PAAF decreased the survival rates in a dose
      dependent manner. Histologically, destruction of vessels, alveolar septal
      thickening, interstitial hypertrophy, and infiltration of inflammatory cells were
      prominent in the lung of PAAF-injected rats. Transcription factor, nuclear factor
      KB (NF-kappaB) was activated and the mRNA levels of tumor necrosis factor-alpha
      and interleukin-1beta were increased in the lung of the PAAF-injected rats. The
      permeability index assessed by Evans blue assay and the lung myeloperoxidase
      activity levels were significantly higher in the PAAF-injected rats than in
      controls. Inhibition of NF-kappaB ameliorated the histologic findings and
      improved the survival rates. Our results suggest that PAAF play a role in the
      pathogenesis of lung injury in severe AP, at least in part through the activation
      of NF-kappaB.

PMID- 11345144
TI  - The role of cyclic AMP in the pathogenesis of glucose desensitization in rat
      pancreatic islets.
AB  - Adenosine-3',5'-cyclic monophosphate (cyclic AMP) promotes exocytosis of insulin
      in pancreatic beta cells. This study was performed to investigate the role of
      cyclic AMP in the pathogenesis of glucose desensitization in rat pancreatic
      islets. In islets cultured with high glucose for 48 hours, 27 mmol/L glucose
      induced insulin release was markedly impaired, while 3.3 mmol/L glucose-or
      arginine-induced insulin release was enhanced, indicating glucose
      desensitization. Islet cyclic AMP content was 190% enhanced in high glucose
      culture islets for 48 hours. In islets cultured with dibutyryl-cyclic AMP
      (dbcAMP) or 3-isobutyl methy-xanthine (IBMX), islet insulin content or 27 mmol/L
      glucose-induced insulin release was deteriorated. In contrast, 3.3 mmol/L glucose
      or arginine-induced insulin release was increased, which was similar to glucose
      desensitized islets. Wash-out of dbc AMP for the last 24 hours of the 48-hour
      culture period restored impaired high glucose-induced insulin release in the same
      manner as wash-out of high glucose. Diazoxide, the KATP channel opener, also
      restored impaired high glucose-induced insulin release from dbcAMP-cultured
      islets. The data suggest that enhancement of cyclic AMP in high glucose-culture
      islets may be one of the pathogenesis of glucose desensitization.

PMID- 11345145
TI  - Involvement of lipid peroxidation in spontaneous pancreatitis in WBN/Kob rats.
AB  - To cast light on the mechanisms underlying development of spontaneous
      pancreatitis lesions, tissues from WBN/Kob rats at various ages were
      histopathologically and immunohistochemically investigated with special reference
      to the existence of the lipid peroxidation products 4-hydroxy-2-nonenal (HNE), 4
      hydroxy-2-hexenal (HHE), and malondialdehyde (MDA). Male 4-20-week-old WBN/Kob
      rats were killed to allow sampling of pancreatic tissues, which were fixed in
      cold acetone and 10% neutral-buffered formalin. and then processed for routine
      histopathology as well as immunohistochemistry for proteins modified by HNE, HHE,
      and MDA. Although no remarkable histologic changes were noted in younger animals,
      edema, hemorrhage, inflammatory cell infiltration, fibrosis, vacuolation of
      acinar cells, and ductular proliferation were observed in exocrine pancreatic
      tissue from animals at 10-15 weeks of age. In animals aged 20 weeks, the lesions
      had progressed remarkably and deposits of hemosiderin were apparent with
      fibrosis. Immunohistochemical examination for lipid peroxidation product-modified
      proteins showed HNE and MDA to be negative in all pancreatic tissues, but HHE was
      positive in the areas involving atrophy of acinar cells and fibrosis in the
      islets. The results of the present study thus provide support for the conclusion
      that lipid peroxidation during spontaneous pancreatitis in WBN/Kob rats may
      possibly be involved in the development of diabetes in this model.

PMID- 11345146
TI  - Necrotizing pancreatitis caused by pancreatic ductal adenocarcinoma.

PMID- 11345147
TI  - Hematocrit determination (HCT) as an early marker associated with necrotizing
      pancreatitis and organ failure.

PMID- 11345148
TI  - Change in tissue kallikrein level in nasal wash after the administration of
      oxatomide in patients with nasal allergy.
AB  - The tissue kallikrein level in the nasal wash was measured before and after 4
      week administration of oxatomide (30 mg per day) in 9 patients with perennial
      allergy. It was found that tissue kallikrein level in the nasal wash obtained
      following provocation tests significantly decreased from 6.05 +/- 4.43 (10(-10)
      mol/hour/L) to 1.84 +/- 0.93 (10(-10) mol/hour/L) after the administration of
      oxatomide. Improvement in subjective symptoms was also observed in all patients
      after the administration. These results would indicate that kinin in the system
      is actively involved in the pathogenesis of nasal allergy.

PMID- 11345149
TI  - The porcine and lagomorph septal cartilages: models for tissue engineering and
      morphologic cartilage research.
AB  - Interest in reconstruction and modification of the facial cartilaginous
      frameworks using advanced technology and instrumentation is growing rapidly.
      Despite this maturing interest, no animal model has been established to provide
      morphologic cartilage tissue with similar characteristics to human septum in
      suitable quantities. The objective of this study was to characterize porcine and
      lagomorph (rabbit) nasal septal cartilage tissue. Both models share great
      similarity with their human counterpart and provide a low-cost, high-volume, and
      easily obtained source of bulk cartilage tissue. We present a technique for
      harvesting intact septal cartilages from these species, and characterize select
      cellular, metabolic, and physical properties using pulse-chase radiolabeling,
      flow cytometry, and mechanical analysis. Our selective evaluation of key tissue
      properties establishes these species as appropriate animal models for nasal
      septal cartilaginous surgery.

PMID- 11345150
TI  - Primary spontaneous cerebrospinal fluid rhinorrhea and obesity.
AB  - The objective of this paper is to determine whether there is a relationship among
      obesity, gender, and the risk of development of primary spontaneous cerebrospinal
      fluid (CSF) rhinorrhea. A retrospective case review of all the patients with CSF
      rhinorrhea treated at our unit over a 10-year period is presented. From a series
      of 20 patients, we studied 9 cases of primary spontaneous CSF rhinorrhea; 6
      patients were female (mean age 50 +/- 10 years) and 3 male (mean age 61 +/- 7
      years). All the female patients were clinically obese, i.e., they had a body mass
      index >30 kg/m2. All the male patients had a body mass index within normal
      parameters. We review the postulated etiologic factors of this uncommon condition
      and study the pathophysiologic basis for obese patients to have CSF rhinorrhea.
      This study suggests a relationship between obese females and the risk of
      developing a primary spontaneous CSF rhinorrhea.

PMID- 11345151
TI  - Bony abnormalities of the paranasal sinuses in patients with Wegener's
      granulomatosis.
AB  - Wegener's granulomatosis is a systemic vasculitis that can affect any organ
      system, but primarily involves the upper and lower respiratory tracts and the
      kidneys. Chronic sinusitis is a well-known clinical feature of the disease.
      Mucosal abnormalities of the nose and paranasal sinuses have been well
      characterized and range from granulomatous lesions to diffuse mucosal thickening.
      In contrast, abnormalities of the underlying bone of the paranasal sinuses in
      this disease have not been well-described, and reports have been limited. To
      characterize bony abnormalities of the nose and paranasal sinuses in patients
      with Wegener's granulomatosis, we performed a retrospective review of all
      patients with Wegener's granulomatosis who underwent a sinus CT scan at our
      institution between 1989 and 1999. Nine patients were identified. A total of 22
      distinct bony abnormalities were identified in 5 patients. Specific bony findings
      included bony erosion and destruction of the septum and turbinates; erosion of
      the ethmoid sinuses; neo-osteogenesis of the maxillary, frontal, and sphenoid
      sinuses; and complete bony obliteration of the maxillary, frontal, and sphenoid
      sinuses. Although these findings are suggestive of Wegener's granulomatosis, they
      are not pathognomonic. Bony changes on sinus CT scan may provide radiologic
      evidence of underlying Wegener's granulomatosis when clinical suspicion is high.

PMID- 11345152
TI  - Unilateral and bilateral effects of nasal septum surgery demonstrated with
      acoustic rhinometry, rhinomanometry, and subjective assessment.
AB  - Little is known of what happens after an operative correction of nasal septum
      deviation in the cavity contralateral to the major septum deviation. We studied
      the effects of septoplasty on the objective and subjective unilateral and
      bilateral nasal airway in 117 consecutive patients presenting for septoplasty due
      to a clinically obstructing septum deviation. Significant median increases in
      nasal flow and cross-sectional areas were noted postoperatively on the deviation
      side, whereas on the contralateral side the nasal flow and the cross-sectional
      area at the nasal valve (MCA1) decreased significantly, the median decreases
      being 19% (p = 0.022) in the flow and 22% (p = 0.0001) in MCA1 before
      decongestion and correspondingly 22% (p = 0.004) and 21% (p = 0.0001) after
      decongestion. Only slight median increases were noted in the bilateral assessment
      postoperatively in these parameters. In the subjective assessment 40% of patients
      were totally free from nasal obstruction postoperatively and the sensation of
      obstruction was low in 35%. An inverse correlation was found between the
      postoperative satisfaction and the decrease in MCA1 on the wide side (r = -0.21,
      p = 0.03) and positive correlations between the postoperative satisfaction and
      the increase in MCA1 on the deviation side (r = 0.26, p = 0.0042) and with the
      bilateral increase in MCA1 (r = 0.20, p = 0.02). The preoperative subjective
      sensation of nasal obstruction correlated significantly with the objective
      parameters on the deviation side, but not with the bilateral parameters. In
      conclusion, it was demonstrated with an objective and subjective assessment that
      correction of a septum deviation may induce harmful effects to the valve area on
      the side contralateral to a deviation. However, postoperatively the overall
      relief of nasal obstruction was good and the satisfaction high in most patients.

PMID- 11345153
TI  - Nasal hyperreactivity among teachers in a school with a long history of moisture
      problems.
AB  - Upper airway symptoms have frequently been reported in people working or residing
      in damp buildings. However, little information has been available on objective
      pathophysiologic findings in relation to these environments. Twenty-eight
      teachers, who had worked for at least five years in a recently renovated school
      that had had severe moisture problems for years, were randomly selected for this
      study. Eighteen teachers, who had worked in another school that had no moisture
      problems, were randomly selected to serve as the control group. Although remedial
      measures had been taken, an increase in the prevalence of mucous membrane
      irritations was still reported by the teachers in the target school. We used a
      nasal challenge test with three concentrations of histamine (1, 2 and 4 mg/mL).
      Recordings of swelling of the nasal mucosa were made with rhinostereometry, a
      very accurate optical non-invasive method. The growth curves of mucosal swelling
      induced by the three concentrations of histamine differed significantly between
      the two groups (p < 0.01). The frequencies of atopy, evaluated with the skin
      prick test, were almost identical in both groups. The study indicates that long
      term exposure to indoor environments with moisture problems may contribute to
      mucosal hyperreactivity, of the upper airways. Such hyperreactivity also seems to
      persist for at least one year after remedial measures have been taken.

PMID- 11345154
TI  - Nasal septal cross-over flap technique: a choanal atresia micro-endoscopic
      surgical repair.
AB  - Choanal atresia is a congenital malformation of the posterior portion of the
      nasal cavity, which is usually unilateral. The incidence is estimated to be 1 in
      5,000 to 8,000 live births. Several surgical approaches have been described to
      correct choanal atresia since Emmert's initial trocar perforation in 1853,
      including transnasal, transpalatal, transseptal, sublabial transseptal,
      transantral, and external rhinoplasty. Although the micro-endoscopic transnasal
      access is a more conservative technique, it allows greater surgical precision,
      and is currently recommended by many authors; choanal atresia repair is still
      considered a challenge, with risks of intraoperative and postoperative
      complications and re-stenosis. This paper reports the results of a series of 33
      patients operated via the transnasal micro-endoscopic surgical approach, and
      describes a new endoscopic technique that the authors call "nasal septal
      crossover flap technique."

PMID- 11345155
TI  - The superior turbinectomy approach to isolated sphenoid sinus disease and to the
      sella turcica.
AB  - Sphenoidotomy or sphenoidectomy are most commonly performed as part of a more
      extensive pansinus procedure. However, rhinologists may find themselves
      occasionally in a need to surgically treat an isolated sphenoid sinus disease.
      With the introduction of endoscopic sinus techniques and instrumentation,
      intranasal sphenoidotomy has become increasingly popular. The most common
      approach used is the intranasal, transethmoid sphenoidectomy. Alternatively, many
      surgeons perform middle turbinectomy to approach the sphenoid sinus transnasally.
      We describe our direct transnasal, nontransethmoid, nontransseptal approach to
      the sphenoid sinus. Superior tubinectomy is performed to enhance the exposure of
      the anterior sphenoid wall. Seventy patients underwent sphenoid sinus exploration
      for isolation sphenoid sinus disease or for pituitary lesions. Surgical goals
      were achieved in all patients and there were no complications related to the
      technique. The superior turbinectomy approach to isolated sphenoid sinus disease
      provides excellent exposure and avoids the sequelae of total ethmoidectomy or
      middle turbinectomy.

PMID- 11345156
TI  - Cost analysis of computer-aided endoscopic sinus surgery.
AB  - Functional endoscopic sinus surgery' (FESS) is a common otolaryngologic
      procedure, with over 250,000 operations performed annually. Computerized surgical
      navigation systems are available to assist the rhinologic surgeon in the complex
      dissection required for FESS. Our objective was to determine whether this system
      provided quantifiable benefits in FESS. We retrospectively reviewed 203 patients
      with chronic sinusitis who underwent endoscopic sinus surgery, and divided them
      into two groups based on whether or not computerized surgical navigation was
      used. There was no statistically significant difference between the two groups in
      terms of surgery duration, extent of surgery, percent of complementary
      procedures, percent of supplementary procedures, complexity of surgery, and
      percent revision surgery. Computer-assisted surgery (CAS) was 6.7% more expensive
      than sinus surgery without computerized surgical navigation (p = 0.01). However,
      the intangible benefits of CAS may outweigh the added expense. (American

PMID- 11345157
TI  - Computed tomography anatomy of the anterior ethmoid canal.
AB  - The roof of the anterior ethmoid swings up anteriorly from its more or less
      horizontal course at the point where the anterior ethmoid canal (AEC) is
      situated. The AEC is an important structure in endoscopic sinus surgery since its
      injury results in bleeding into the nasal cavity and may result in intraorbital
      bleeding. We therefore investigated the location of this canal and the anatomic
      characteristics of the area surrounding the canal using coronal computed
      tomography (CT) of the paranasal sinuses. One hundred sides of 50 paranasal
      coronal CT images in patients with sinusitis were analyzed to assess the location
      of the AEC, the shape of the superolateral wall of the ethmoid sinus anterior and
      posterior to the AEC, and pneumatization of the roof of the anterior ethmoid
      sinus. The AEC is situated in the second quarter of the roof of the ethmoid
      sinus. The superolateral wall anterior to the AEC demonstrated an acute angle in
      99% of sides, while the superolateral wall posterior to the AEC showed an obtuse
      angle in 87% of sides. The ethmoid cell anterior to the AEC pneumatized
      posteriorly over the AEC in 26% of sides. We conclude that coronal CT
      confirmation of the anatomic characteristics of the AEC, and the area surrounding
      the canal, is invaluable for preoperative planning for endoscopic sinus surgery.

PMID- 11345159
TI  - Scanning electron microscopy of hydroxylated polyvinyl acetal and conventional
      gauze strip nasal packing materials.
AB  - The application of nasal packing is one of the most commonly performed procedures
      in rhinology. Various materials have been used as nasal packing, including
      conventional gauze strips and hydroxylated polyvinyl acetal. Complications
      related to nasal packing may cause problems that lead to increased morbidity.
      Among those complications, infectious ones range from localized infection in the
      nasal cavity to toxic shock syndrome. The purpose of this study was to evaluate
      conventional gauze strips and hydroxylated polyvinyl acetal nasal packing
      materials by scanning electron microscopy, to reveal their surface
      characteristics that would promote or prevent the development of infectious
      complications. The two types of materials were examined before and after
      application into the nasal cavity. Scanning electron microscopy demonstrated that
      hydroxylated polyvinyl acetal material had a smooth surface, whereas conventional
      gauze strips had an irregular surface with fibers projecting, thus increasing the
      surface area for bacterial adherence and allowing possible evasion of bacteria
      from the elements of the immune system within this fibrillar structure.

PMID- 11345158
TI  - Comparative oral and topical decongestant effects of phenylpropanolamine and d
      pseudoephedrine.
AB  - Nonselective adrenergic alpha-agonists such as phenylpropanolamine and d
      pseudoephedrine are widely used as decongestants to treat nasal congestion
      associated with a variety of nasal diseases. Although the activity of these drugs
      is well established in clinical studies, a direct comparison of their nasal
      decongestant effect as determined by changes in nasal cavity dimensions and nasal
      architecture has not been studied. Using acoustic rhinometry, we evaluated the
      effects of these drugs on nasal cavity volume, minimum cross-sectional area
      (Amin), and the distance from the nosepiece to the Amin (Dmin) in a feline,
      pharmacological model of nasal congestion. Administration of topical compound
      48/80 (1%), a mast cell histamine liberator, into the left nasal passageway
      decreased nasal volume by 66%, reduced Amin by 51%, and increased Dmin by 116%.
      The congestive responses to compound 48/80 (1%) were reproducible through six
      weeks. In a subset of cats, the nasal cavity volume effect of repetitive exposure
      to compound 48/80, given once every two weeks for six weeks, was not different
      from the nasal responses after the initial exposure to compound 48/80.
      Pretreatment with oral phenylpropanolamine (10 mg/kg) or oral d-pseudoephedrine
      (10 mg/kg) attenuated the nasal effects of compound 48/80, but were associated
      with a pronounced increase in systolic blood pressure of +51 and +82 mmHg,
      respectively. A similar decongestant profile was observed with
      phenylpropanolamine (1%) and d-pseudoephedrine (1%) when given topically. Topical
      phenylpropanolamine (1%) and d-pseudoephedrine (1%) 45 minutes after dosing
      increased blood pressure +44 and +17 mmHg, respectively, over control animals. We
      conclude that oral and topical phenylpropanolamine and d-pseudoephedrine display
      equieffective nasal decongestant activity and produce similar cardiovascular
      profiles characterized by significant increases in blood pressure.

PMID- 11345160
TI  - Dichotomous physiological effects of nocturnal external nasal dilation in heavy
      snorers: the answer to a rhinologic controversy?
AB  - The purpose of this article was to study the impact of external dilation on nasal
      airway dimensions, sleep architecture, and snoring. Eighteen heavy snorers
      without severe obstructive sleep apnea syndrome (mean apnea-hypopnea index (AHI)
      9.3) reporting nocturnal nasal obstruction were enrolled in a randomized
      (controlled) cross-over study, evaluating subjective and objective effects of
      external nasal dilation (Breathe Right, 3M). The active dilator was also worn
      during a one-week pretrial run-in period. Polysomnography, recording of snoring
      sounds, and repeated acoustic rhinometry were performed on two consecutive
      nights, one with the active dilator and one with a placebo strip. The significant
      subjective improvement reported during the run-in period compared to the
      preceding period without dilator (p < 0.01), remained only for nasal patency (p <
      0.05) when comparing the two nights in the sleep laboratory. The nasal dimensions
      increased significantly (p < 0.001) with the active dilator compared to placebo,
      both in the evening and the next morning. In a subgroup (n = 6) of habitual
      snorers (AHI < 10) with severe morning obstruction (combined minimal cross
      sectional area < 0.6 cm2), external dilation significantly improved the mean
      sleep PaSO2 (92.4 --> 96.7) and the percentage of sleep with a PaSO2 < 95% (49.9%
      --> 4.9%) (p < 0.05). In this subgroup there was a trend toward reduction in (7.4
      --> 5.4) (p = 0.06), whereas the AHI increased significantly in the group of 12
      with larger nocturnal nasal dimensions (p < 0.05). Duration and intensity of
      snoring remained unchanged regardless of the subgrouping. Objective beneficial
      effects were restricted to nocturnal oxygen saturation and AHI in a subgroup of
      habitual heavy snorers identified by repeated acoustic rhinometry, in whom
      external dilation objectively relieved marked nocturnal nasal obstruction. This
      finding may provide a logical explanation for the conflicting results of medical,
      surgical, and mechanical expansion of the nasal dimensions on snoring and sleep
      disturbances. (American

PMID- 11345161
TI  - A randomised-controlled clinical trial methodology for evaluating the teaching
      utility of interactive educational diabetes simulators.
AB  - AIDA is an interactive educational diabetes simulator which has been made
      available without charge on the Internet. Since its launch on the World Wide Web
      in 1996 over 58,000 people have visited the AIDA Web site (http://www.2aida.org)
      and over 17,500 copies of the program have been downloaded from there free-of
      charge. The AIDA software is believed to be of use in recreating clinical
      (diabetes) situations for interactive simulation. However, despite its widespread
      usage, its actual utility for supporting the education of patients with Type 1
      diabetes mellitus remains to be objectively demonstrated in a randomised
      controlled clinical trial setting. This paper describes a prospective, randomised
      controlled trial (RCT) methodology for formally evaluating the educational
      utility of an interactive diabetes simulator, like AIDA. The protocol makes use
      of two study arms, each receiving different educational interventions. During
      lessons, Arm A of the study will be exposed to the AIDA simulator (the active
      intervention), while Arm B (the control group) will benefit from conventional
      educational methods using standard presentations with slides and transparencies.
      Six lessons will be held for each study arm (one per week). At the beginning and
      end of the study self-monitoring blood glucose (SMBG) data will be collected,
      details of any hypoglycaemic episodes recorded, and assessments made of HbA1c.
      Participants will also be required to complete a detailed questionnaire to assess
      their self-confidence, quality of life and metabolic control, attitudes towards
      SMBG, and knowledge about insulin dosage calculation. Comparisons will be made
      between Arm A and Arm B using unpaired statistical analyses. A partial cross-over
      study design is also proposed whereby subsequently the control group will be
      exposed to the AIDA simulator during a further 6-week course of lessons. This
      will ensure that the maximum number of subjects will eventually receive the
      active intervention, and will also allow further within group paired analyses to
      be applied (with greater statistical power). An initial evaluation study using
      this RCT approach has just recently commenced in the Ospedale di Marino in Marino
      (Rome), Italy.

PMID- 11345162
TI  - Relation between plasma leptin and anthropometric and metabolic covariates in
      lean and obese diabetic and hyperlipidaemic Asian Northern Indian subjects.
AB  - This study investigated the relationship of plasma leptin to obesity, diabetes
      and hyperlipidaemia in Asian Northern Indian subjects, considered to have a
      predisposition to abdominal obesity and metabolic syndrome. A total of 72
      subjects, subcategorised into lean and obese healthy subjects, lean and obese
      Type 2 diabetic and lean and obese non-diabetic hyperlipidaemic subjects were
      recruited. High leptin values were observed in all obese groups, and obese
      diabetic patients showed the highest levels. In lean and obese diabetic subjects,
      plasma leptin did not show any correlation to any index of glycaemia. When all
      lean and all obese subjects were analysed in two separate groups, body mass index
      (BMI), percent total body fat, and body density significantly correlated with the
      plasma leptin levels (p<0.05). Leptin values, when correlated to all variables in
      all patients taken together, showed the greatest magnitude of correlation with
      BMI (r=0.64), percent total body fat (r=0.67), and waist circumference (r=0.51).
      Strong inverse correlation was seen with body density (r=-0.67). Levels of serum
      insulin did not show any correlation with leptin levels in all subjects combined,
      and separately in various groups. Multiple linear regression analysis performed
      in obese, non-diabetic and normolipidaemic subjects, all Type 2 diabetic and all
      non-diabetic hyperlipidaemic subjects separately showed that percent total body
      fat is the only significant predictor of plasma leptin concentration in all the 3
      groups. The present study suggests that plasma leptin has a strong positive
      correlation with percent total body fat in Asian Northern Indian subjects. Among
      other components of metabolic syndrome, only abdominal obesity is weakly
      correlated to serum leptin levels.

PMID- 11345163
TI  - HDL oxidability and its protective effect against LDL oxidation in Type 2
      diabetic patients.
AB  - Low density lipoprotein (LDL) oxidation is a crucial step in the atherosclerotic
      process. High density lipoprotein (HDL)-associated enzymes such as paraoxonase
      could exert a protective effect on LDL oxidation in the arterial wall, an effect
      which could be impaired in Type 2 diabetes mellitus (T2DM). We studied copper
      induced oxidation in LDL and HDL isolated from 17 T2DM patients with fair
      glycaemic control and HDL-cholesterol within normal range and 17 healthy
      normolipidaemic control subjects. To evaluate the effect of HDL on LDL oxidation
      in diabetic and control subjects, we assessed copper-induced oxidation in HDL/LDL
      mixtures, with each lipoprotein isolated from the same subject. Relationships
      with HDL chemical composition, alpha-tocopherol content and serum paraoxonase
      activity were investigated. Oxidation was promoted by lipoprotein incubation with
      copper and then thiobarbituric acid reactive substances (TBARS), conjugated diene
      production and electrophoretic mobility in agarose gel were measured. In T2DM
      subjects HDL oxidation was higher than in controls. However, HDL from diabetics
      was as effective as control HDL to inhibit LDL oxidation. Neither HDL chemical
      composition nor serum paraoxonase activity showed any difference as compared to
      control subjects. In contrast, HDL from T2DM subjects showed a higher alpha
      tocopherol content which positively correlated with HDL oxidability. Paraoxonase
      activity positively and strongly correlated with HDL inhibitory effect on LDL
      oxidation in patients and controls belonging to the heterozygous activity
      phenotype. Besides, LDL oxidability showed no differences between patients and
      controls. These results suggest that fairly-controlled T2DM patients with HDL
      cholesterol levels within normal range show: 1) normal HDL ability to inhibit LDL
      oxidation related to normal paraoxonase activity; 2) higher HDL oxidability in
      spite of its high alpha-tocopherol content, which could favour tocopherol
      mediated peroxidation and 3) normal LDL oxidability possibly due to the lack of
      significant lipoprotein structural alterations.

PMID- 11345164
TI  - Screening for coeliac disease in families of adults with Type 1 diabetes based on
      serological markers.
AB  - The prevalence of coeliac disease (CD) in the adult population is unknown because
      silent and latent stages do exist. Type 1 diabetes mellitus may be associated
      with CD because of common genetic background and/or shared pathogenetic
      mechanisms. We investigated 74 adults with type 1 diabetes (32+/-11 yr, disease
      duration 13+/-9 yr), 69 parents of diabetic probands (56+/-10 yr), 59 siblings
      (30+/-11 yr) and 50 healthy controls (35+/-10 yr) for the presence of circulating
      islet cell antibodies (ICA), anti-glutamic acid decarboxylase antibodies
      (GADA65), anti-gliadin immunoglobulins A and G (IgA- and IgG-AGA). All patients
      with raised AGA, performed also IgA anti-endomysium antibody (EmA) indirect
      immunofluorescence assay. Samples were positive for ICA in 19 diabetics (26%), 4
      parents (6%), 4 siblings (7%), 0 controls (p<0.001); for GADA in 34 diabetics
      (46%), 4 parents (6%), 1 sibling (2%), 0 controls (p<0.001). Twenty-five diabetic
      patients (34%), 10 parents (14%), 5 siblings (8%), 3 controls (6%) (p<0.001) had
      raised IgA-AGA (>4.4 mg/l). Four diabetic patients (5%), 5 parents (7%), 0
      siblings (0%), 4 controls (8%) had raised IgG-AGA (>18 mg/l). Both IgA- and IgG
      AGA were detected in 1 diabetic and 2 parents. The prevalence of ICA, GADA, and
      IgA-AGA positivity in Type 1 diabetes patients was significantly higher than in
      controls (p<0.001). Finally, 50 AGA-positive subjects performed EmA test: only 2
      of them resulted EmA-positive, a diabetic patient and a sibling. The patient with
      Type 1 diabetes had a small-bowel biopsy specimen consistent with CD and, as sole
      evidence of malabsorption, sideropenic anaemia. EmA-positive sibling also showed
      severe iron deficiency, yet refused endoscopy. We conclude that: 1) CD cannot be
      diagnosed on the basis of associated IgA- and IgG-AGA alone. Nevertheless,
      detection of such antibodies is useful, in combination with EmA, in screening for
      endoscopic biopsy; 2) too high rate of detection of IgA-AGA in Type 1 diabetic
      patients in comparison with other groups excludes a false positivity of the test
      itself, while suggests a pathogenetic association of both immunological
      disorders, perhaps related to abnormal gammadelta TCR-bearing intraepithelial
      lymphocytes.

PMID- 11345165
TI  - Glycaemic and insulinaemic indices of Mexican foods high in complex carbohydrates
      in Type 2 diabetic subjects.
AB  - The glycaemic (GI) and insulinaemic indices (InIn) of 3 indigenous single foods
      and 3 indigenous realistic high complex carbohydrate meals (bread=100) were
      determined in 7 Mexican type 2 diabetic subjects. Observed GI (mean+/-SEM) were:
      beans (B) 39.9+/-7.3, wheat tortilla (WT) 53.2+6.4, corn tortilla (CT) 84.8+/
      6.0, wheat tortilla beans taco (BWT) 71.2+/-9.5, corn tortilla beans taco (BCT)
      73.5+/-4.3 and corn tortilla potato taco (PT) 121.5+/-12.8. The GI of white bread
      (WB) was higher than B (p<0.01), WT (p<0.01), BWT (p<0.05) and BCT (p<0.05) and
      did not differ from CT and PT. Observed InIn were: B 36.2+/-7.0, WT 49+/-5.6, CT
      83.4+/-17.6, BWT 66.1+/-5.9, BCT 80.3+/-7.9 and PT 164.2+/-26.5. InIn of B, WT
      and BWT were lower than WB (p<0.01), whereas PT was higher (p<0.05) and CT and
      BCT did not differ. Diabetic subjects do not have to eliminate WT, B or beans
      tacos, as suggested by some physicians. Nevertheless, they could lower the
      consumption of CT and PT. This information presents an alternative to diabetic
      subjects to live and eat more freely, by preventing the alteration of familiar
      and dining cultural habits.

PMID- 11345166
TI  - Aerobic and anaerobic performance before and after a short-term body mass
      reduction program in obese subjects.
AB  - The cardiovascular response to an aerobic cycloergometer exercise test (ACET, 15
      min at 60 W, 60 rpm) and the maximally attainable muscle power output, assessed
      by a stair climbing test (SCT), were evaluated in 60 obese patients (41 females
      and 19 males; age: 18-68 yr; body mass index, BMI: 40.8+/-4.8 kg/m2) before and
      after a 3-week body mass reduction (BMR) program, entailing integrated energy
      restricted diet (1200-1500 kcal/day), low-grade aerobic exercise conditioning and
      individual and/or group psychological therapy. The daily conditioning protocol (5
      days/week) consisted of: 1) 30 min of indoor jogging and dynamic aerobic standing
      and floor exercises performed with arms and legs, under the guidance of a
      therapist; 2) 30 min of cycloergometer exercise at 60 W; and/or 3) 4-km outdoor
      leisure walking on flat terrain. Three weeks of BMR program induced a significant
      weight loss (-4.5 %; p<0.001), a reduction of systolic (-11+/-14 mmHg, 
      7.3%,p<0.001) and diastolic (-7+/-9 mmHg, -7.3%,p<0.001) resting arterial blood
      pressure, as well as a reduction of heart rate at rest (-18.6%,p<0.001), during
      ACET (-11.3%,p<0.001) and 5 min thereafter (-14.8%,p<0.001). The subjective
      rating of perceived exertion in terms of breathlessness and general fatigue
      during ACET, scored on a 0-100 visual analogic scale, was significantly reduced
      (p<0.001) after BMR program. A 11.2% decrease in SCT time (p<0.001) was also
      observed, corresponding to a 9.6% increase (p<0.001) in average muscle power (W)
      and 14.6% increase (p<0.001) in specific muscle power (W.kg(-1)). In conclusion,
      a combination of energy restricted diet, low intensity aerobic exercise and
      psychological counselling appears to significantly improve both aerobic and
      anaerobic performance in morbidly obese subjects. Different factors (ie,
      reduction of body mass, shift in the balance between parasympathetic and
      sympathetic activity, a weight-loss dependent shift toward a more favourable
      region of the muscle power-velocity curve, acquisition of a certain degree of
      motor skillfulness during the conditioning program, improvement of self-esteem
      and motivation) might be responsible, alone or in combination, for these short
      term positive effects of BMR program.

PMID- 11345167
TI  - Carotid intima-media thickness in patients with Type 2 diabetes and
      hypercholesterolemia.
AB  - Both patients with Type 2 diabetes mellitus (T2DM) and with hypercholesterolemia
      have a more extensive and accelerated atherosclerosis with higher common carotid
      artery intima-media thickness (CIMT) values than the general population. The aim
      of this study was to compare the CIMT in polygenic hypercholesterolemia (HP;
      n=41: 30 females and 11 males, aged 52+/-15 yr) and in T2DM (n=43: 22 females and
      21 males, aged 59+/-11 yr), with a duration of disease less than 5 yr and no
      evidence of coronary heart disease. A control group (C) of 40 sex- and age
      matched healthy subjects was studied. We evaluated the CIMT on the far wall of
      the distal segment of the common carotid arteries on sites free of plaque. The
      mean of the CIMT measurements (Tmean; 9 on each side) and the maximal CIMT
      measured (Tmax) were used as the representative values for each subject. Tmax
      values were 0.96+/-0.2 mm and 0.82+/-0.2 mm in T2DM and HP, respectively, which
      were significantly higher than C (0.74+/-0.1 mm). Corresponding values of Tmean
      were 0.8+/-0.1 mm and 0.71+/-0.2 mm, both significantly higher than C (0.68+/-0.1
      mm). In HP, both Tmax and Tmean values were positively correlated to age
      (p=0.0001 and p=0.0001, respectively), body mass index (BMI; p=0.05 and p=0.05,
      respectively), presence of hypertension (p=0.003 and p=0.0008, respectively) and
      fibrinogen (p=0.0009 and p=0.001, respectively); Tmean was also correlated to
      apolipoprotein B (ApoB; p=0.03). The multiple "stepwise" regression analysis
      revealed fibrinogen and age as the only significant determinants of Tmax and
      Tmean. In T2DM Tmax and Tmean were positively correlated to age only (p=0.04 and
      p=0.01, respectively). In conclusion, T2DM patients have a more accelerated
      atherosclerosis than subjects with HP. This is evident after a short duration of
      disease, probably for a longer latency period of disease and the presence of
      multiple risk factors.

PMID- 11345168
TI  - Medical therapy of brain edema in fulminant hepatic failure? Are we there yet?

PMID- 11345169
TI  - American Liver Foundation releases Pediatric Liver Research Agenda-2000.

PMID- 11345170
TI  - Oral tolerance and its role in clinical disease.

PMID- 11345171
TI  - The nutritional and safety assessment of breast milk substitutes and other
      dietary products for infants: a commentary by the ESPGHAN Committee on Nutrition.

PMID- 11345172
TI  - PH monitoring in the distal and proximal esophagus in symptomatic infants.
AB  - BACKGROUND: Standard distal esophageal pH monitoring data are sometimes within
      normal ranges in children with clinically suspected gastroesophageal reflux
      disease. Therefore, the authors hypothesized that the amount of acid reflux
      reaching the proximal esophagus may be greater in some subgroups of patients than
      in healthy controls or in other subgroups of patients. METHODS: The parameters of
      24-hour pH monitoring in the proximal part of the esophagus were analyzed in 120
      symptomatic infants in who the reflux parameters in the lower esophagus were
      clearly within normal ranges (reflux index < 5.0%). The infants were classified
      into four patient groups: excessive regurgitation (n = 41): inconsolable crying
      (n = 31), apparent life-threatening event (ALTE) (n = 18), and chronic
      respiratory disorders (n = 30). The control group consisted also of 120 infants.
      The following parameters were calculated: reflux index, the number of reflux
      episodes, the number of reflux episodes lasting longer than 5 minutes, the
      duration of the longest reflux episode, and the acid clearance time (ACT,
      duration of reflux episodes divided by number of reflux episodes). RESULTS: The
      patients with chronic respiratory disorders were significantly older than the
      patients in the other groups and the controls. In the distal esophagus, there was
      no statistically significant difference between the reflux parameters. As could
      be expected, every parameter was statistically (paired t test, Wilcoxon signed
      rank test) significantly smaller in the proximal than in the distal esophagus,
      except for the ACT in infants who presented with inconsolable crying. In the
      proximal esophagus, there was no statistically significant difference between the
      different patient subgroups or controls, except for the number of reflux episodes
      in the group with chronic respiratory disorders and the group with inconsolable
      crying, applying one-way analysis of variance. As determined by applying the Mann
      Whitney test, the number of reflux episodes in the upper esophagus was
      significantly higher in the group with chronic respiratory disorders than in the
      other patient groups and controls. Therefore, the authors' data do not support
      the hypothesis that reflux reaching the proximal esophagus is a frequent cause of
      ALTE. However, the data may suggest that the number of reflux episodes reaching
      the proximal esophagus in children with chronic respiratory disorders and with
      distal pH monitoring data within normal ranges may be increased. Whether this
      finding reflects reality or a statistical coincidence, or is influenced by the
      older age of this patient group, needs further evaluation. CONCLUSIONS: In
      theory, dual simultaneous esophageal pH monitoring in the distal and proximal
      esophagus may increase the diagnostic accuracy of pH monitoring in infants. Our
      results do not support a substantial advantage of a systematic application of
      this new technique, especially not in infants presenting with ALTE, excessive
      regurgitation, or inconsolable crying. In the subgroup of patients with chronic
      respiratory disorders, more data are needed before conclusions can be determined
      and recommendations can be made.

PMID- 11345173
TI  - Outcome of early hepatic portoenterostomy for biliary atresia.
AB  - BACKGROUND: The outcome of the hepatic portoenterostomy (Kasai) procedure for
      biliary atresia is improved when it is performed before 90 days of age. However,
      it is not known whether intervention before 30 days is better than intervention
      between 30 and 90 days. METHODS: The authors reviewed the records of all patients
      seen by the Pediatric Gastroenterology Service at St. Louis Children's Hospital
      from 1984-1999 to ascertain the outcome of patients who underwent Kasai procedure
      before or after 30 days of age. RESULTS: Of 92 patients with biliary atresia
      treated at St. Louis Children's Hospital over 15 years, 9 underwent the Kasai
      procedure before 30 days of age. Liver transplantation was necessary in 77.8% of
      these patients at a mean age of 11.0 +/- 4.26 months, as compared with 53.4% at
      32.14 +/- 7.14 months for the remainder of the patients who underwent the
      procedure after 30 days of age. CONCLUSIONS: Although these data suggest that
      outcomes are worse for patients who undergo the procedure before 30 days of age,
      they may reflect a difference in the pathogenesis of biliary atresia that brings
      it to clinical attention earlier and may provide further evidence that biliary
      atresia is a phenotype for a number of distinct underlying disease processes.

PMID- 11345174
TI  - Ursodeoxycholic acid ameliorates ibuprofen-induced enteropathy in the rat.
AB  - BACKGROUND: The objective of the study was to determine whether ursodeoxycholic
      acid (Ursodiol) is protective against ibuprofen (IBU)-induced enteropathy.
      METHODS: Using the chronically catheterized rat model, IBU (60 mg/kg body weight
      per day) was infused via the gastric catheter twice daily. Pancreatic enzyme (PE;
      10,000 U lipase/kg body weight per day) and Ursodiol (10 mg/kg body weight per
      day) in two doses were infused via the duodenal catheter. Rats were assigned to
      one of six treatment groups and were administered treatment for 20 days: control,
      IBU, PE, IBU + PE, IBU + Ursodiol, and IBU + PE + Ursodiol. The entire jejunum,
      ileum, cecum, and colon were available for histologic analysis using previously
      described techniques. RESULTS: Addition of Ursodiol to high-dose IBU and normal
      doses of PE showed a significant reduction in the percentage of rats with ulcers
      (P < 0.05), total number of serositis events (P < 0.01), total number of severe
      ulcers (P < 0.001), and an absence of ulcers in the large intestine. CONCLUSIONS:
      Ursodiol, the drug of choice for the treatment of cystic fibrosis liver disease,
      may offer a safe method of using high-dose IBU in these patients by ameliorating
      the enteropathy.

PMID- 11345175
TI  - Wide variety of genotypes and geographic origins of hepatitis B virus in Belgian
      children.
AB  - BACKGROUND: Belgium is a country with low endemicity for hepatitis B virus (HBV)
      infection. Few data are available on genotypes or serotypes of HBV among infected
      children. METHODS: The S region of the hepatitis B virus genome was amplified and
      sequenced in 23 children treated with interferon-alpha in Belgium. Nucleotide
      sequences were aligned and compared with other known sequences in a phylogenetic
      analysis. RESULTS: A high stability of the S gene was observed during treatment.
      Four genotypes were represented in this sample of Belgian patients (A, B, D, and
      E), reflecting the geographic diversity of origins. CONCLUSIONS: In this series,
      the wide variety of geographic origins is confirmed by the molecular
      characteristics of HBV. In Belgium, HBV infection of children is currently
      essentially an imported infection.

PMID- 11345176
TI  - Technetium-99m HMPAO-labeled leukocyte imaging compared with endoscopy,
      ultrasonography, and contrast radiology in children with inflammatory bowel
      disease.
AB  - BACKGROUND: The purpose of this study was to evaluate retrospectively the value
      of leukocyte-labeled scintigraphy, ultrasonography, and contrast radiography
      compared with endoscopy in children suspected of having inflammatory bowel
      disease (IBD). METHODS: Twenty-eight children (17 boys; mean age, 10.2 years)
      with IBD based on standard colonoscopic, histologic, and radiologic criteria (16
      with Crohn's disease, 5 with ulcerative colitis, 5 with nonspecific colitis, I
      with granulomatous disease, and I with Beh,cet's disease) were included.
      Endoscopic, ultrasonographic, and contrast radiologic examinations were realized
      for 28, 23, and 19 children respectively. RESULTS: Sensitivity and specificity
      were 75% and 92% for leukocyte-labeled scintigraphy, 39% and 90% for
      ultrasonography, and 58% and 83% for contrast radiography. The authors noted
      discontinuous uptake for 14 of 15 true-positive results for patients with Crohn's
      disease and continuous uptake for 4 of 4 true-positive results for patients with
      ulcerative colitis. A negative correlation between scan activity index and Lloyd
      Still clinical score was found for 11 patients with Crohn's disease (r = -0.77).
      CONCLUSIONS: Leukocyte-labeled scintigraphy, a noninvasive and reproducible
      technique, is a useful tool in the diagnosis and therapeutic strategy of IBD, and
      provides information on the presence, the intensity, and the extent of the
      disease, particularly in the terminal ileum. Leukocyte-labeled scintigraphy may
      not replace colonoscopy with biopsies for diagnosis confirmation. Its reliability
      seems higher than that of ultrasonography.

PMID- 11345177
TI  - Bilirubin-IXbeta is a marker of meconium, like zinc coproporphyrin.
AB  - BACKGROUND: Because meconium accumulates continuously in the fetal intestine,
      analysis of the postnatally excreted material could yield important information
      of intrauterine metabolism and maturation. Therefore, a study of the bilirubin
      pigments in meconium and in the first neonatal stools was carried out. METHODS:
      Meconium and stools from 37 neonates of various gestational ages were collected
      carefully, and stored at -20 degrees C, protected by aluminium foil. Samples were
      defrosted, vortex mixed with an equal amount of dimethyl sulfoxide, centrifuged,
      and submitted to analysis by high-pressure liquid chromatography using newly
      developed methods to identify and to quantitate the bilirubin-IXalpha, -IXbeta, 
      IXgamma, and -IXdelta isomers. In addition, samples were also submitted to diazo
      coupling with ethyl anthranilate. Total coproporphyrins and zinc coproporphyrin
      were assayed for comparison. RESULTS: Unconjugated bilirubin-IXalpha and -IXbeta
      were detected in meconium but not the -IXgamma or the -IXbeta isomer. Bilirubin
      IXbeta was the predominant pigment and comprised 63% to 96% of the unconjugated
      bilirubins in the first sample of meconium excreted. Its amount decreased rapidly
      during the first 5 days in full-term newborns, but this occurred more slowly in
      preterm neonates, especially in those with a gestational age less than 30 weeks.
      The decrease of bilirubin-IXbeta over time correlated with that of
      coproporphyrin. CONCLUSIONS: Bilirubin-IXbeta is the prevailing bile pigment in
      the first excreted sample of meconium. It gradually decreases after birth and can
      be considered a biochemical marker of meconium, like zinc coproporphyrin.

PMID- 11345178
TI  - Is there a relation between docosahexaenoic acid concentration in mothers' milk
      and visual development in term infants?
AB  - BACKGROUND: Docosahexaenoic acid (DHA), present in high concentrations in the
      brain and retina, has a role in visual development. DHA is present in human milk,
      but not in most infant formulas. It is, however, under discussion whether DHA
      should be added to formulas intended for term infants. The concentration of DHA
      in human milk, which is influenced by maternal diet, varies considerably, but it
      is unknown whether this variation affects visual development in term infants.
      METHODS: The authors investigated 39 4-month-old fully breast-fed term infants in
      a cross-sectional study. Visual acuity was measured by swept visual evoked
      potentials, milk DHA was determined by gas chromatography, and maternal fish
      intake was assessed by a frequency questionnaire. RESULTS: Frequency of fish
      intake correlated positively to the DHA level in breast-milk (P = 0.001). Mothers
      who ate fish the day before sampling had a milk DHA level higher than expected
      from habitual fish intake (P = 0.002). If this was taken into account, 57% of the
      variation in milk DHA could be explained by fish intake. Multiple linear
      regression analysis revealed a significant association between visual acuity and
      milk DHA (P = 0.02, R2 = 0.09). CONCLUSION: This finding suggests a cause-and
      effect relationship between infant milk DHA intake and visual acuity. If these
      data are confirmed, there is a need to consider the optimal intake of DHA for the
      lactating mother.

PMID- 11345179
TI  - Oroesophageal motor disorders in Pierre Robin syndrome.
AB  - BACKGROUND: Feeding disorders are one of the main clinical features in PRS, which
      combines a posterior U-shaped cleft palate, retrognathia, and glossoptosis. The
      aim of this study was to evaluate the oral and esophageal motor function of
      children with PRS without additional neurologic symptoms. METHODS: All children
      hospitalized with Pierre Robin syndrome either isolated (n = 27) or associated
      with Stickler syndrome (n = 8) were included. Clinical evaluation of their
      oroesophageal disorders and systematic esophageal manometry were performed.
      RESULTS: Feeding disorders were always present, but type of disorder varied from
      one child to another. Esophageal disorders were frequent and seemed to be
      resistant to classic gastroesophageal reflux treatment. Eighty-six percent of the
      children required nasogastric tube feeding for a mean duration of 8.6 months.
      Esophageal manometric abnormalities were noted in 50% of the children: lower
      esophageal sphincter hypertonia, failure of lower esophageal sphincter relaxation
      at deglutition, and esophageal dyskinesia. These clinical and manometric
      disorders showed a trend to spontaneous regression after 12 months. CONCLUSION:
      In the current Pierre Robin syndrome series, clinical and manometric anomalies of
      oroesophageal motility were always present. The authors identified an unusual
      manometric pattern that has also been described in situations of neurovegetative
      instability. It could reflect dysregulation of the control of the central pattern
      generators of swallowing in the brain stem.

PMID- 11345180
TI  - Extensive and partial protein hydrolysate preterm formulas: the effect on growth
      rate, protein metabolism indices, and plasma amino acid concentrations.
AB  - BACKGROUND: The use of protein hydrolysate preterm formulas is restricted because
      data on their nutritional adequacy are scarce. The authors evaluated the rate of
      growth and indices of protein metabolism in low-birth weight infants fed
      extensive and partial protein hydrolysate preterm formula followed for 12 weeks.
      METHODS: A total of 61 low-birth weight infants were assigned randomly to receive
      extensive protein hydrolysate preterm formula (EH: n = 16), partial protein
      hydrolysate preterm formula (PH: n = 15), and standard preterm formula (SF; n =
      15), or were fed their own mother's fortified breast milk (FBM; n = 15). The
      infants were investigated at study entry, and at 4, 8, and 12 weeks after study
      entry. RESULTS: There were no differences with respect to growth rate (weight
      gain, increments in length and head circumference), urea, albumin, prealbumin,
      transferrin, and plasma amino acid concentrations (except for tyrosine on a
      single occasion) according to the degree of hydrolysis. There were also no
      differences between groups fed hydrolyzed formulas and SF. However, several
      differences were found when EH and PH were compared with FBM. Weight gain from
      the entry to 12 weeks, serum urea at 12 weeks, and total plasma essential amino
      acids at 8 weeks were significantly higher in groups fed EH and PH than in those
      fed FBM. In addition, valine was significantly higher in groups fed PH (P < 0.05)
      than in the group fed FBM at 8 and 12 weeks, tyrosine was higher in EH and PH in
      comparison with FBM at 4 weeks, and in PH versus FBM at 12 weeks after study
      entry. CONCLUSIONS: This study suggests that experimental EH and PH are at least
      nutritionally equivalent to SFs.

PMID- 11345181
TI  - Clinical quiz. Abetalipoproteinemia.

PMID- 11345182
TI  - Duodenal tube test in the diagnosis of biliary atresia.
AB  - BACKGROUND: Biliary atresia (BA) is the main cause of severe liver damage in
      infants. Successful surgical treatment is related directly to an early and rapid
      diagnosis. The aim of this study was to determine specificity, sensitivity, and
      predictive value of the duodenal tube test (DTT) in the diagnosis of BA in a
      series of infants with cholestatic jaundice. METHODS: This was a descriptive
      study of a series of infants with cholestatic jaundice created to validate the
      sensitivity, specificity, and predictive value of the DTT in the diagnosis of BA.
      A total of 254 patients were identified from 1988 to 1998. The study cohort
      included 137 male infants (53.9%), and the mean age on admission was 8.3 weeks +/
      2.47 weeks (standard deviation). Study protocol included liver function tests,
      liver ultrasound, metabolic screening and serology for viral hepatitis, and
      toxoplasma, rubella, cytomegalovirus, herpes, and others. A nasoduodenal tube
      was, placed at the distal duodenum and the fluid was collected for 24 hours. DTT
      was considered bile positive when yellow biliary fluid was observed; the test was
      concluded at this time. When no yellow biliary duodenal fluid was observed, the
      collection was continued for 24 hours and, if negative, was reported as bile
      negative. The patients with a bile-positive DTT were not explored surgically, and
      the cholestasis workup was completed. Laparotomy and a surgical cholangiogram
      were indicated in patients with bile-negative DTT. If BA was verified,
      portoenterostomy was performed. The gold standard for BA diagnosis was the
      following: obstruction of the biliary tract confirmed by laparotomy and a
      surgical cholangiogram, and clinical outcome in patients without laparotomy
      (followed for a minimum of 18 months). RESULTS: The results are as follows. BA:
      bile-positive DTT, n = 3; bile-negative DTT, n = 108. No BA: bile- positive DTT,
      n = 134; bile-negative DTT, n = 9. The following values were also determined:
      sensitivity, 97.3%; specificity, 93.7%; positive predictive value, 92.3%; and
      negative predictive value, 98.5%. The final diagnoses were as follows: BA, n =
      111 (43.7%); neonatal hepatitis syndrome, n = 103 (40.6%); cholestasis associated
      with inspissated bile syndrome, n = 13 (5.1%); choledochal cyst, n = 11 (4.3%);
      galactosemia, n = 9 (3.5%); cirrhosis of unknown etiology, n = 5 (2%), and
      Alagille syndrome, n = 2 (0.8%). CONCLUSIONS: The data obtained from this series
      validate the DTT as a useful clinical tool for the differential diagnosis of the
      infant with cholestasis, particularly for indicating laparotomy and cholangiogram
      to substantiate BA. This diagnostic test is quick and simple, and offers the
      clinician valuable information with which to determine whether surgical
      intervention is necessary.

PMID- 11345183
TI  - Parenteral multivitamin supplementation induces both oxidant and antioxidant
      responses in the liver of newborn guinea pigs.
AB  - BACKGROUND: The multivitamin solution is a major component of photo-induced
      generation of peroxides in parenteral nutrition. The aim of this study was to
      determine whether the parenteral multivitamin preparation induces in the liver a
      peroxide-induced oxidant challenge or an antioxidant protection associated with
      the antiradical components of the solution. METHODS: Newborn guinea pigs were
      infused with dextrose supplemented with peroxides (250 micromol/L H2O2 or 350
      micromol/L tert-butylhydroperoxide) or with a multivitamin preparation (MVP, 1%
      vol/vol). After 4 days, total glutathione and a free radical-sensitive eicosanoid
      marker (prostaglandin I2 [PGI2]/total prostaglandins) were measured in livers.
      RESULTS: There was a significant decrease in the PGI2/total prostaglandin ratio
      (mean +/- SEM) [dextrose: 0.068 +/- 0.007 vs. (dextrose + H2O2: 0.048 +/- 0.001,
      dextrose + TBH: 0.043 +/- 0.001)] and glutathione concentrations decreased
      [dextrose: 55 +/- 7 vs. (dextrose + H2O2: 37 +/- 7, dextrose + TBH: 18 +/- 7
      nmol/mg protein)] after infusion of peroxides. Despite the peroxide load in the
      multivitamin solution, it did not alter the measured variables as prostanoid
      ratio remained at control concentrations (dextrose: 0.066 +/- 0.008 vs. dextrose
      + MVP: 0.065 +/- 0.006), as did glutathione levels (dextrose: 52 +/- 6 vs.
      dextrose + MVP: 45 +/- 7 nmol/mg prot). CONCLUSION: In the liver of guinea pig
      pups, infused peroxides cause oxidation of membrane-derived prostanoids. The
      decrease in glutathione in response to administration of peroxides suggests
      consumption rather than a response to a free radical attack. Despite the oxidant
      load associated with peroxides generated in MVP, the multivitamin preparation
      protected membranes as the prostanoid ratio, and glutathione levels remained at
      control levels.

PMID- 11345184
TI  - Thalidomide-induced sensory neuropathy.

PMID- 11345185
TI  - Eosinophilic colitis: a rare entity.

PMID- 11345186
TI  - A rare cause of high transaminasemia: autosomal muscle dystrophy with gamma
      sarcoglycan.

PMID- 11345187
TI  - Giant cell hepatitis with autoimmune hemolytic anemia and hemophagocytosis.

PMID- 11345188
TI  - Eosinophilic gastroenteritis complicated with perforation and intussusception in
      a neonate.

PMID- 11345189
TI  - Re: unusual early presentation of Gilbert syndrome in pediatric recipients of
      liver transplantation.

PMID- 11345190
TI  - Apoptosis and gastrointestinal disease.

PMID- 11345191
TI  - Granulomatosis cheilitis and Crohn disease.

PMID- 11345192
TI  - Role of Jak kinases and STATs in cytokine signal transduction.
AB  - The Janus family tyrosine kinase-signal transducer and activator of transcription
      (Jak-STAT) signaling pathway is broadly used by interferons and type I cytokines.
      These cytokines and interferons activate Janus family tyrosine kinases (Jak
      kinases), which in turn phosphorylate and thereby activate STAT proteins. Before
      activation, STAT proteins are cytosolic proteins; after activation, however, they
      are translocated to the nucleus where they function as transcription factors.
      This review summarizes salient features of the Jak-STAT pathway and focuses on
      the functional role of the different Jak kinases and STATs in vivo.

PMID- 11345194
TI  - Negative regulators of cytokine signaling.
AB  - The interaction of a cytokine with its specific cell surface receptor triggers
      the activation of intracellular signaling pathways that ultimately program the
      cellular response. Although the specific components and actions of the pathways
      driving these responses, such as the Janus kinase (JAK)/signal transducers and
      activators of transcription (STAT) pathway, are relatively well defined, it is
      becoming clear that important mechanisms exist to restrain these signaling
      cascades. This review discusses the key biochemical actions and biological roles
      of the phosphatase SHP-1, the protein inhibitors of activated STATs (PIAS) and
      the suppressor of cytokine signaling (SOCS) protein family in the negative
      regulation of cytokine signal transduction.

PMID- 11345195
TI  - Structural and functional hot spots in cytokine receptors.
AB  - The activation of cytokine receptors is a stepwise process that depends on their
      specific interaction with cognate cytokines, the formation of oligomeric receptor
      complexes, and the initiation of cytoplasmic phosphorylation events. The recent
      determination of the structure of extracellular domains of several cytokine
      receptors allows comparison of their cytokine-binding surfaces. This comparison
      reveals a common structural framework that supports considerable diversity and
      adaptability of the binding surfaces that determine both the specificity and the
      orientation of subunits in the active receptor complex. These regions of the
      cytokine receptors have been targeted for the development of specific agonists
      and antagonists. The physical coupling of signaling intermediates to the
      intracellular domains of their receptors plays a major role in determining
      biological responses to cytokines. In this review, we focus principally on the
      receptors for cytokines of the granulocyte-macrophage colony-stimulating factor
      (GM-CSF) family and, where appropriate, compare them with related cytokine
      receptors. Several paradigms are beginning to emerge that focus on the ability of
      the extracellular portion of the cytokine receptor to recognize the appropriate
      cytokine and on a phosphorylated motif in the intracellular region of the GM-CSF
      receptor that couples to a specific signaling pathway.

PMID- 11345193
TI  - Mechanisms of transformation by the BCR/ABL oncogene.
AB  - The Philadelphia chromosome generates a chimeric oncogene in which the BCR and c
      ABL genes are fused. The product of this oncogene, BCR/ABL, has elevated ABL
      tyrosine kinase activity, relocates to the cytoskeleton, and phosphorylates
      multiple cellular substrates. BCR/ABL transforms hematopoietic cells and exerts a
      wide variety of biological effects, including reduction in growth factor
      dependence, enhanced viability, and altered adhesion of chronic myelocytic
      leukemia (CML) cells. Elevated tyrosine kinase activity of BCR/ABL is critical
      for activating downstream signal transduction and for all aspects of
      transformation. This review will describe mechanisms of transformation by the
      BCR/ABL oncogene and opportunities for clinical intervention with specific signal
      transduction inhibitors such as STI-571 in CML.

PMID- 11345197
TI  - Quantitative monitoring of circulating Epstein-Barr virus DNA for predicting the
      development of posttransplantation lymphoproliferative disease.
AB  - Epstein-Barr virus (EBV)-DNA was quantitatively measured to assess
      posttransplantation virus reactivation by real-time polymerase chain reaction
      (PCR). In the first retrospective analysis of a 7-year-old boy with
      lymphoproliferative disease (LPD) after an unrelated cord blood transplantation,
      serum EBV-DNA progressively increased to 4 x 10(5) copies/mL. EBV load was then
      prospectively monitored in peripheral blood from posttransplantation patients.
      The second case was an 8 year-old boy with aplastic anemia who received a CD34+
      cell transplantation. This patient died of LPD with the progression of pulmonary
      nodules. EBV-DNA increased to 4 x 10(4) copies/mL after the control of
      cytomegalovirus reactivation. On the other hand, EBV-DNA was undetectable (<200
      copies/mL) in the series of all 58 samples from 10 patients who did not develop
      LPD after hematopoietic stem cell transplantation. Sequential monitoring of
      circulating EBV-DNA by quantitative PCR may be a useful indicator for predicting
      the development of posttransplantation LPD.

PMID- 11345198
TI  - Platelet-derived growth factor enhances granulopoiesis via bone marrow stromal
      cells.
AB  - Platelet-derived growth factor (PDGF), a growth factor for connective tissue
      cells, stimulates erythropoiesis and megakaryocytopoiesis in vitro but the effect
      of PDGF on granulocyte proliferation remains unknown. The effect of the
      recombinant human PDGF-BB isoform on granulopoiesis was investigated in this
      study. The results show that PDGF significantly stimulated murine colony-forming
      unit-granulocyte-monocyte (CFU-GM) proliferation in a dose-dependent manner (1 to
      100 ng/mL) using murine bone marrow cells (n = 4). Maximum stimulation was
      obtained with 50 ng/mL of PDGF (P < .01). The effect of PDGF on murine CFU-GM
      proliferation was compared with that of interleukin (IL)-3, IL-6, granulocyte
      monocyte colony-stimulating factor (GM-CSF), and acidic fibroblast growth factor
      (aFGF) at their optimal doses. The stimulating activity of PDGF was higher than
      that of aFGF but lower than that of IL-3, IL-6, or GM-CSF. There is no
      synergistic effect between PDGF and IL-3 or IL-6, but a significant enhancing
      effect was observed in IL-3 plus IL-6. PDGF also stimulated the growth of CFU-GM
      with CFU-megakaryocyte in the presence of bone marrow stromal cells. We also
      found that PDGF had similar a effect on human CFU-GM proliferation using bone
      marrow mononuclear cells (MNC). However, the increase in PDGF-stimulated CFU-GM
      proliferation was inhibited by anti-GM-CSF, anti-IL-3, and anti-IL-6 antibodies
      (n = 4), suggesting that endogenously produced GM-CSF, IL-3, and IL-6 may play a
      role in the PDGF-induced CFU-GM proliferation. Furthermore, PDGF (1 to 100 ng/mL)
      did not show any effect on CFU-GM proliferation when replacing bone marrow MNC
      with immunomagnetic selection-enriched CD34+ cells from human cord blood (n = 5;
      purity, 91% +/- 6.5%). This study indicates that PDGF may indirectly enhance CFU
      GM proliferation by inducing the bone marrow stromal cells to produce GM-CSF, IL
      3, or IL-6.

PMID- 11345199
TI  - Differential susceptibility of quiescent CD4+ lymphocytes to syncytial-inducing
      and non-syncytial-inducing isolates of HIV-1.
AB  - It is generally believed that quiescent CD4+ T cells are not susceptible to HIV-1
      infection. However, infection of unstimulated peripheral mononuclear cells by
      syncytial-inducing (SI) viruses has been shown to be much more efficient than
      with non-syncytial-inducing (NSI) viruses. This suggested that SI, CXCR4-tropic
      viruses may be able to infect quiescent CD4+ T cells. We studied the infection of
      highly purified quiescent CD4+ T cells by SI and NSI viruses. In this article we
      show that although NSI viruses failed to significantly infect quiescent cells, SI
      viruses consistently infected these cells and produced viruses upon cellular
      activation by interleukin-2, 2 to 7 days after initial infection. To examine
      whether the difference was the result of viral or host factors, we purified CCR5+
      quiescent CD4+ T cells and showed that these cells can be infected by dual tropic
      (R5X4) but not by R5 virus. This indicated that CCR5+ quiescent T cells were also
      susceptible to HIV-1 infection, and the failure of NSI, CCR5-tropic viruses to
      infect quiescent cells may be due to some intrinsic properties of these viruses.

PMID- 11345200
TI  - Increased frequency of monoclonal gammopathy of undetermined significance in
      patients with nonimmune chronic idiopathic neutropenia syndrome.
AB  - This study describes the frequency of monoclonal gammopathy of undetermined
      significance (MGUS) and the changes in some inflammation-related serum proteins
      in 157 patients with nonimmune chronic idiopathic neutropenia syndrome (NI-CINS).
      Of these patients, 42 had pronounced neutropenia with neutrophil counts <
      1500/microL, and 115 had mild neutropenia with neutrophil counts ranging from
      1500 to 2499/microL. Sixty-six volunteers served as healthy control subjects and
      157 age- and sex-matched patients hospitalized for nonmalignant diseases served
      as patient control subjects. We found that 28.6% of patients with pronounced
      neutropenia and 14.8% of patients with mild neutropenia had increased serum gamma
      globulins (above the 95% confidence limit of values of the control subjects). In
      the group of patients with pronounced neutropenia, 30.9% had increased
      immunoglobulin (Ig)G values and 23.8% had increased IgA values. In the group of
      patients with mild neutropenia, 17.4% had increased IgG values and 21.7% had
      increased IgA values. IgG and IgA values strongly correlated with the neutrophil
      count. No changes in serum IgM were found. Three of 42 patients with pronounced
      neutropenia (7.14%) and 3 of 115 patients with mild neutropenia (2.61%) had serum
      immunofixation tests which showed a small monoclonal spike--4 were IgG-kappa
      type, 1 was IgG-lambda type, and 1 was IgA-kappa type. None of the healthy or
      patient control subjects had any evidence of MGUS. No significant changes in the
      amount of monoclonal spikes were documented during an 18- to 143-month follow-up
      (median, 58 months). Except for significantly increased alpha1-antitrypsin
      levels, there were no significant differences in the levels of acute-phase
      proteins studied between the study patients and the control subjects. These
      findings are consistent with our previous report suggesting the possible
      existence of an unrecognized low-grade chronic inflammation in patients with NI
      CINS, which may be involved in the pathogenesis of neutropenia in the affected
      subjects.

PMID- 11345196
TI  - Molecular biology of chronic myeloid leukemia.
AB  - Multistep carcinogenesis is exemplified by chronic myeloid leukemia with clinical
      manifestation consisting of a chronic phase and blast crisis. Pathological
      generation of BCR-ABL (breakpoint cluster region-Abelson) results in growth
      promotion, differentiation, resistance to apoptosis, and defect in DNA repair in
      targeted blood cells. Domains in BCR and ABL sequences work in concert to elicit
      a variety of leukemogenic signals including Ras, STAT5 (signal transducer and
      activator of transcription-5), Myc, cyclin D1, P13 (phosphatidylinositol 3
      kinase), RIN1 (Ras interaction/interference), and activation of actin
      cytoskeleton. However, the mechanism of differentiation of transformed cells is
      poorly understood. A mutator phenotype of BCR-ABL could explain the
      transformation to blast crisis. The aim of this review is to integrate molecular
      and biological information on BCR, ABL, and BCR-ABL and to focus on how signaling
      from those molecules mirrors the biological phenotypes of chronic myeloid
      leukemia.

PMID- 11345201
TI  - Autoimmune neutropenia with cyclic oscillation of neutrophil count after steroid
      administration.
AB  - A 16-year-old female patient was evaluated for pancytopenia. She had a white
      blood cell count of 1.6 x 10(9)/L with 0.02 neutrophils and a platelet count of
      19 x 10(9)/L. In the bone marrow, mature granulocytes were markedly decreased in
      number, but no atypical cells were present. Antineutrophil antibody was
      demonstrated by flow cytometry, and the level of platelet-associated
      immunoglobulin G was increased. A diagnosis of autoimmune neutropenia and
      thrombocytopenia was made. Interestingly, neutrophil and platelet counts
      fluctuated cyclically after the initiation of prednisolone therapy. The
      neutrophil count fluctuated between 0.1 x 10(9)/L and 7 x 10(9)/L, and the
      platelet count fluctuated between 19 x 10(9)/L and 175 x 10(9)/L, in 4-week
      cycles. Following splenectomy, neutrophil and platelet counts normalized. We
      believe the immune mechanism of recurrent neutropenia in this patient differs
      from that in other patients with cyclic neutropenia reported with stem cell
      disorders.

PMID- 11345202
TI  - Successful combination therapy--flunarizine, pentoxifylline, and cholestyramine-
      for spur cell anemia.
AB  - Spur cell anemia, a hemolytic anemia observed in patients with alcoholic
      cirrhosis, is characterized by unusual erythrocyte morphology and an increased
      ratio of free cholesterol to phospholipid in the erythrocyte membrane. The
      prognosis of spur cell anemia is usually extremely poor, however, we describe
      here a patient with spur cell anemia who was successfully treated with
      combination therapy consisting of flunarizine, pentoxifylline, and
      cholestyramine. Initial therapy with flunarizine alone for 6 weeks did not
      significantly decrease the number of spur cells on peripheral blood smears. So
      pentoxifylline was added to the regimen. The patient recovered from the anemia,
      showed remarkable improvement with regard to the hyperbilirubinemia, and the
      changes were accompanied by a significant decrease in the number of spur cells in
      peripheral blood smears. To correct the hypercholesterolemia, cholestyramine was
      added to the regimen, which resulted in a reduction in the serum level of free
      cholesterol and an increase in the molar ratio of free cholesterol to
      phospholipid in erythrocyte membrane. However, 6 months later a skin eruption
      developed that was considered an adverse reaction to the drugs, so the
      flunarizine and pentoxifylline were discontinued. With cholestyramine therapy
      alone, the remission of spur cell anemia was maintained for more than 11 months.
      These observations suggest that non-invasive combination therapy with
      flunarizine, pentoxifylline, and cholestyramine is effective and valuable in the
      treatment of patients with spur cell anemia.

PMID- 11345203
TI  - Improvement of splenomegaly and pancytopenia by enzyme replacement therapy
      against type 1 Gaucher disease: a report of sibling cases.
AB  - Gaucher disease is a genetic lipid storage disease and represents a potentially
      serious health problem. It arises from a deficiency of glucocerebrosidase
      activity with secondary accumulation of large quantities of glucocerebroside.
      Symptoms are usually multisystemic, often debilitating or disabling, and
      sometimes disfiguring, and they can lead to death. We report objective clinical
      response's to repeated infusion of human placental and recombinant
      glucocerebrosidase in 2 patients with type 1 Gaucher disease and increased
      hemoglobin levels and platelet counts. Splenic volume decreased during the period
      of enzyme administration. Enzyme replacement therapy has improved the treatment
      of type 1 Gaucher disease by safely and effectively arresting, decreasing, or
      normalizing many of its major signs and symptoms. Consideration by physicians
      must be given to Gaucher disease, and appropriate treatments must be given when
      confronted with cryptogenic pancytopenia or hepatosplenomegaly.

PMID- 11345204
TI  - Assessment of prognostic factors in follicular lymphoma patients.
AB  - Prognostic factors, including clinical, biological, and histological parameters,
      were assessed for 94 patients with follicular lymphomas at our institute.
      Follicular lymphomas constituted 7.7% (94/1208) of malignant lymphomas in this
      study. Eighteen patients were diagnosed with stage I follicular lymphoma, 20 with
      stage II, 23 with stage III, and 33 with stage IV. The cases of follicular
      lymphoma were subclassified as: follicular small cleaved cell lymphoma (FSC) in
      20 cases, follicular mixed cell lymphoma (FMX) in 59 cases, and follicular large
      cell lymphoma (FLC) in 15 cases. The patients comprised 49 men and 45 women with
      a median age of 54 years (range, 25-84 years). The complete response rate was
      76.5%, and the median survival time was 13 years. The expected 10-year overall
      survival and event-free survival rates were 61.9% and 38.2%, respectively.
      Univariate analysis identified the factors associated with poor survival as
      elevated serum lactate dehydrogenase (LDH) level (P < .0001), age of >60 (P <
      .0001), Ann Arbor stage III/IV (P < .01), and Eastern Cooperative Oncology Group
      performance status (PS) of 2 to 4 (P = .048). Multivariate analysis showed that
      LDH, age, and PS were independent predictors. After application of the
      International Prognostic Index (IPI), the 10-year survival rates for the low
      risk, low-intermediate risk, high-intermediate risk and high-risk groups were
      80.4%, 48.7%, 21.9%, and 0.0%, respectively. The differences among these groups
      were significant at P < .01. The IPI for aggressive non-Hodgkin's lymphoma was
      found to be applicable to survival prediction for Japanese follicular lymphoma
      patients.

PMID- 11345206
TI  - Antitumor immunity induced by irradiated tumor cells producing macrophage colony
      stimulating factor.
AB  - We previously reported that administration into mice of mouse lymphoid leukemia
      L1210 cells engineered to secrete macrophage colony-stimulating factor (M-CSF)
      could lead to tumor rejection. Here, we demonstrate that inoculation with
      irradiated M-CSF-producing cells protects mice against a subsequent challenge
      with unmodified parental tumor cells. We used 2 experimental protocols: the
      inoculation with irradiated M-CSF-producing L1210 cells (EM5) before the
      challenge with parental cells and after the challenge with parental cells. Both
      protocols effectively improved the survival rate of mice compared with protocols
      in which irradiated non-M-CSF-producing L1210 cells (EM-mock) were inoculated.
      Inoculation with 1 x 10(2) irradiated EM5 cells was sufficient to prolong the
      survival time of mice subsequently challenged with 1 x 10(4) parental cells. In
      vivo depletion experiments with administration of antibodies suggested the
      involvement of CD4+ T cells, CD8+ T cells, and natural killer (NK) cells in the
      antitumor effect. Consistent with these findings, the cytotoxic T lymphocyte
      activity of splenocytes from EM5-inoculated mice was higher than that from EM
      mock-inoculated mice, and L1210 tumors were heavily infiltrated by CD4+ T cells
      and NK cells as well as macrophages in EM5-inoculated mice.

PMID- 11345207
TI  - Analysis of clonal relationship using single-cell polymerase chain reaction in a
      patient with concomitant mantle cell lymphoma and multiple myeloma.
AB  - We report a case of concomitant mantle cell lymphoma (MCL) and multiple myeloma
      (MM) in which we investigated the possibility of a clonal relationship. A 76-year
      old man was diagnosed with MCL [immunoglobulin (Ig)M,D-kappa; stage IVB] and MM
      (IgG-kappa; stage I). Ig heavy chain (IgH) gene complementarity-determining
      region 3 in DNA from both the MCL tumor and from single MM cells from bone marrow
      smears was amplified to investigate whether there was a clonal relationship
      between MCL and MM. Sequence analysis revealed no clonal relationship between MCL
      and MM in our patient.

PMID- 11345208
TI  - Acute spontaneous tumor-lysis syndrome in a pregnant woman with non-Hodgkin's
      lymphoma.
AB  - Both non-Hodgkin's lymphoma (NHL) in pregnancy and acute spontaneous tumor-lysis
      (ASTL) syndrome are rare. Here we present a 32-year-old Egyptian woman in the
      27th week of pregnancy, who was admitted with epistaxis, lethargy, vomiting and
      dehydration. This patient developed ASTL syndrome secondary to undiagnosed NHL,
      but was not on any medication associated with the syndrome. At 28 weeks, she gave
      birth to a healthy baby who, unfortunately, died within a few days. To our
      knowledge, this is the first case of ASTL syndrome in a pregnant woman.

PMID- 11345205
TI  - Long-term outcome of treatment with protocols AL841, AL851, and ALHR88 in
      children with acute lymphoblastic leukemia: results obtained by the Kyushu
      Yamaguchi Children's Cancer Study Group.
AB  - We analyzed the long-term outcome and late effects of treatment in 187 patients
      with childhood acute lymphoblastic leukemia (ALL) diagnosed between 1984 and
      1990. Overall survival and event-free survival rates were 68.2% +/- 3.7% and
      63.2% +/- 3.6% at 15 years, respectively. Of 55 patients who relapsed after
      achieving the first complete remission (CR), only 17.4% were rescued by salvage
      therapy. The advantage of stem cell transplantation over chemotherapy was
      observed only in those patients with bone marrow relapse during therapy. The SD
      for score height in patients maintaining the first CR significantly decreased at
      the time of final follow-up compared with that at diagnosis: 0.059 to -0.800 (P <
      .0001). The decrease was remarkable in patients younger than 5 years at
      diagnosis. Other late effects included mild liver dysfunction in 18% and
      hepatitis C virus infection in 9%. Congestive heart failure was observed in only
      2.9% of patients despite the high cumulative dose of daunorubicin (450 mg/m2).
      Although the survival rates of patients on our protocols were comparable to those
      of other study groups, some modification, including reduction in dose of cranial
      irradiation and/or anticancer drugs, should be considered to reduce late adverse
      effects in survivors of childhood ALL.

PMID- 11345209
TI  - One missense mutation in the factor X gene causing factor X deficiency--factor X
      Kanazawa.
AB  - We investigated the molecular basis of factor X deficiency in a Japanese patient
      whose factor X activity and antigen level were 45% and 50% of normal control
      values, respectively. All exons and intron/exon junctions of the factor X gene
      were studied using a strategy combining polymerase chain reaction (PCR)
      amplification and nonradioactive single-strand conformational polymorphism (SSCP)
      analysis. Exon 5, containing the DNA fragment of the proband, showed aberrant
      migration by SSCP analysis. All exon-containing DNA fragments amplified by PCR
      were sequenced, and it was revealed that the proband was a heterozygote for a G -
      > A substitution in exon 5 of the factor X gene of the proband. This mutation
      predicts an amino acid replacement of arginine (Arg) for glycine (Gly) at codon
      114 in the second EGF-like domain.

PMID- 11345210
TI  - Antithrombotic effects of tetramethylpyrazine in in vivo experiments.
AB  - In this study, tetramethylpyrazine (TMPZ) was effective in reducing the mortality
      of ADP-induced acute pulmonary thromboembolism in mice when administered
      intravenously at doses of 40 and 80 microg/g. In addition, intravenous injection
      of TMPZ (10 microg/g) significantly prolonged the bleeding time by approximately
      1.5-fold compared with normal saline in severed mesenteric arteries of rats.
      Continuous infusion of TMPZ (1 microg/g per min) for 10 minutes also
      significantly increased the bleeding time approximately 1.6-fold, and the
      bleeding time returned to baseline within 60 minutes after cessation of TMPZ
      infusion. On the other hand, platelet thrombi formation was induced by
      irradiation of mesenteric venules with filtered light in mice pre-treated
      intravenously with fluorescein sodium (10 microg/kg). When it was intravenously
      injected, TMPZ (250 microg/g) significantly prolonged the latent period of the
      induction of platelet plug formation in mesenteric venules. TMPZ (250 microg/g)
      prolonged occlusion time approximately 1.4-fold (183 +/- 18 seconds) compared
      with that of normal saline (132 +/- 14 seconds). Furthermore, aspirin (300
      microg/g) showed similar activity in the prolongation of occlusion time in this
      experiment. In conclusion, these results suggest that TMPZ has effective
      antithrombotic activity in vivo and may be a potential therapeutic agent for
      arterial thrombosis but must be assessed further for toxicity.

PMID- 11345211
TI  - Breast carcinoma presenting as immune thrombocytopenic purpura.

PMID- 11345212
TI  - BCG: the challenge continues.
AB  - It is widely recognized that BCG provides inconsistent and often inadequate
      protection against tuberculosis; however, simple estimates of efficacy fail to
      reflect the complexity of protection within, let alone between, populations. A
      decline in protection with an increase in age at vaccination has been seen in
      many studies. This may reflect 2 things: (i) that as people age they are exposed
      to a variety of mycobacterial challenges which may interfere with, or mask, the
      protection of BCG; and/or (ii) that the vaccine is better at protecting against
      primary disease than against either reactivation- or reinfection-type disease.
      These factors need to be taken into consideration when interpreting the results
      obtained with screening vaccines in animal models, as most of these models mimic
      acute primary-type disease. In addition, we have no evidence that the protection
      induced by BCG lasts for > 15 y, in any population. Recent data from South India
      indicate a complex interaction of age and time effects: BCG imparted consistent
      protection in children, but no protection for subjects > 15 y old, and may even
      have imparted negative protection among these older individuals. If true, these
      findings have important implications for efforts to develop a vaccine against
      adult pulmonary tuberculosis.

PMID- 11345213
TI  - Tuberculosis DNA vaccines.
AB  - DNA vaccines have been the subject of intense investigation for the past 10 y,
      during which time several tuberculosis (TB) DNA vaccines have been shown to
      confer protective immunity in animal models. So far, proof of principle for
      priming of immune responses by a naked DNA vaccine (malaria) has been
      demonstrated in humans, but potency remains a significant limitation. However,
      new DNA vaccine formulations and delivery systems are being developed with
      markedly improved potency in animal models. Therefore, there is a clear path to
      the human clinical testing of TB DNA vaccines.

PMID- 11345214
TI  - Correlation between BCG genomics and protective efficacy.
AB  - Between the derivation of bacille Calmette-Guerin (BCG) vaccine in 1921 and the
      lyophilization of BCG daughter strains in the 1960s, a number of clinical trials
      were performed looking at the protective efficacy of BCG vaccination against
      tuberculosis. These trials differed from one another in a number of ways: they
      employed different methodologies for delivering the vaccine and interpreting
      outcomes; they were performed on populations with different genetic backgrounds
      and different levels of exposure to environmental Mycobacteria; and, finally,
      they used different BCG vaccine strains. The results of these trials were
      estimates of protective efficacy against pulmonary tuberculosis ranging from
      about 80% to nil. Because of the differences in outcomes and confounding
      variables, it is difficult to conclude whether differences in interventions alone
      may have contributed to the remarkably variable results. Analysis of BCG vaccines
      used in clinical trials suggests a trend towards decreasing efficacy with
      increased passage in the laboratory; however, trials that used relatively "older"
      BCG strains were generally performed at different sites than trials which used
      "younger" BCG strains. Genomic analysis of BCG vaccines demonstrates that during
      the half-century of ongoing passage of BCG vaccines in vitro there have been
      numerous genetic changes, comprising single nucleotide polymorphisms,
      duplications and deletions. The impact of these changes in the BCG genome on the
      protective efficacy observed in field trials remains to be determined.

PMID- 11345215
TI  - A case for a neonatal, low-dose BCG vaccination trial.
AB  - The rational design of a successful vaccination strategy against tuberculosis
      requires certain kinds of information and must take account of several
      considerations: (i) the nature of the immune response that protects the large
      majority of individuals infected by Mycobacterium tuberculosis, designated as
      healthy contacts, must be defined and distinguished from that in tuberculosis
      patients, whose immune system must have failed; (ii) the vaccination strategy
      must incorporate a way of priming the immune system to guarantee in all
      individuals this protective response, normally generated in healthy contacts,
      upon natural infection by M. tuberculosis; (iii) the strategy must incorporate a
      mechanism for ensuring that the effectiveness of this priming is not abrogated by
      exposure to environmental mycobacteria; and (iv) the strategy must take account
      of the fact that the vaccinated population is genetically heterogeneous, and that
      individuals will therefore respond variably to most standard vaccination
      protocols. We describe a tentative proposal for how these interrelated problems
      might be solved and discuss predictions of this tentative vaccination strategy.
      Critical testing of the neonatal, low-dose BCG vaccination strategy can only be
      achieved by a field trial and we outline the considerations underlying this
      proposal.

PMID- 11345216
TI  - Follow-up of patients treated with oral doxycycline for Lyme neuroborreliosis.
AB  - The clinical outcome for 69 patients treated with oral doxycycline for Lyme
      neuroborreliosis was studied retrospectively. The clinical follow-up time was 14
      d to 2 y (median 7 months). All patients improved during and after treatment. A
      complete recovery was seen in 56 patients by 14 d to 9 months (median 6 weeks)
      after therapy, while 13 patients (19%) still had persistent sequelae 1 y after
      antibiotic treatment. Six patients were retreated because of new or persistent
      symptoms, but in no patient was a treatment failure proven. A questionnaire was
      sent to each patient, asking for time to recovery, sequelae and relapse of
      symptoms. No patient had experienced relapse of symptoms associated with Lyme
      neuroborreliosis when answering the questionnaire 2-9 y after treatment. Oral
      doxycycline seems to be an effective, convenient and inexpensive alternative for
      the treatment of Lyme neuroborreliosis.

PMID- 11345217
TI  - Haemophilus influenzae osteomyelitis in adults: a report of 4 frontal bone
      infections and a review of the literature.
AB  - Haemophilus influenzae occasionally causes hematogenous long-bone osteomyelitis
      in children. In adults, however, bone infections caused by this organism are
      extremely rare. We report four adult cases of H. influenzae frontal bone
      osteomyelitis and review 12 cases from the literature.

PMID- 11345218
TI  - Prevalence of and detection of resistance to ampicillin and other beta-lactam
      antibiotics in Haemophilus influenzae in Denmark.
AB  - The susceptibility of Haemophilus influenzae to penicillin V and G, ampicillin
      and cefuroxime was investigated by MIC, disc and tablet diffusion methods, using
      chocolate agar as test medium, to determine the prevalence of ampicillin
      resistant isolates and the optimal method for their detection. Eighty-six
      isolates were clinical isolates collected prospectively from July to September
      1998 and 22 isolates were clinical isolates with decreased susceptibility to
      ampicillin previously referred to the reference laboratory. Eighty-seven isolates
      were ampicillin-susceptible and 16 were ampicillin-resistant. Thirteen produced
      beta-lactamases. Among the consecutive isolates 12.8% were resistant. With each
      of the Rosco Neo-sensitabs containing penicillin G, 2.5 microg ampicillin and 33
      microg ampicillin, 3 very major errors occurred (resistant isolates
      misinterpreted as susceptible) and 5-13 major errors (susceptible isolates
      misinterpreted as resistant). The AB biodisk containing ampicillin (10 microg)
      was superior to the penicillin V and G discs, i.e. only 1 very major error
      occurred and major and minor errors were infrequent. The cefuroxime disc
      identified 4/8 beta-lactamase-negative ampicillin-resistant isolates. Thus, for
      susceptibility testing with chocolate agar as test medium, the use of an inoculum
      of 10(5) colony-forming units, 10 microg ampicillin discs and interpretative zone
      diameters of > or = 28 mm indicating susceptibility and < or = 25 mm indicating
      resistance was found to produce reliable identification of ampicillin-resistant
      isolates of H. influenzae.

PMID- 11345219
TI  - Epidemiological analysis of Salmonella enterica serotype typhimurium from Hong
      Kong by ribotyping and pulsed-field gel electrophoresis.
AB  - We investigated the antimicrobial susceptibilities and molecular epidemiology of
      200 strains of Salmonella enterica serotype typhimurium isolated from 1989 to
      1996 in Hong Kong. Only 22% of strains were susceptible to all 19 antibiotics
      tested but all were susceptible to second- and third-generation cephalosporins.
      Up to 9% of strains were resistant to 0.12 mg/l concentrations of ciprofloxacin
      or ofloxacin but none were resistant to 1 or 2 mg/l concentrations of these 2
      drugs, respectively. The isolates were grouped into 15 types by ribotyping with
      restriction endonuclease EcoRI and into 53 types by pulsed-field gel
      electrophoresis of XbaI-restricted DNA fragments. When DNA fragments of the
      ribotypes and pulsotypes were pooled and analyzed 87 types resulted, 76 (87%) of
      which were of > 90% similarity and were grouped into 15 clusters. About 60% of
      the isolates belonged to 3 clusters, which probably represented 3 clones endemic
      in the community. The rest of the isolates were of a large variety of types or
      clusters. For epidemiological purposes analysis of pooled results from different
      molecular techniques would be more discriminative than results from individual
      techniques alone.

PMID- 11345220
TI  - Diagnostic evaluation of urinary lipoarabinomannan at an Ethiopian tuberculosis
      centre.
AB  - Direct capture enzyme-linked immunosorbent assay (ELISA) for lipoarabinomannan
      (LAM) was performed on urine samples from 200 tuberculosis (TB) patients and 800
      non-TB patients routinely diagnosed among consecutive suspects in an Ethiopian TB
      centre. 50 healthy Ethiopians, 50 healthy individuals and 100 non-TB patients
      from Norway served as controls. Of the TB patients, 139 (69.5%) were positive for
      acid-fast bacilli (AFB). In the remaining cases the diagnosis was based on
      suggestive clinical findings. All Ethiopian non-TB patients were AFB negative and
      showed no clinical evidence of TB. In the Ethiopian groups, 148 (74%) of the TB
      patients, 105 (13.1%) of the non-TB patients and 5 (10%) of the healthy controls
      were positive by the LAM-ELISA. 113 (81.3%) of AFB positives and 35 (57.4%) of
      AFB-negative TB patients had positive LAM-ELISA. In the Norwegian groups all were
      LAM negative. The sensitivity and specificity of the LAM-ELISA for TB patients
      versus Ethiopian non-TB patients were 74% and 86.9%, respectively; the positive
      and negative predictive values were 58.5% and 93.0%. This study suggests that
      detection of LAM in the urine of TB patients may improve case finding and that
      diagnostic tests based on this principle may serve as valuable supplemental tools
      in TB control.

PMID- 11345221
TI  - Genotypes of clustered cases of Pneumocystis carinii pneumonia.
AB  - Reports of outbreaks of Pneumocystis carinii pneumonia (PCP) among human
      immunodeficiency virus-negative immunocompromised patients have suggested a
      person-to-person transmission of P. carinii. In this study, 17 bronchoalveolar
      lavage isolates from patients in 3 PCP outbreaks were genotyped, 2 in renal
      transplant recipients and 1 outbreak among patients with haematological
      disorders. Genotypes in the P. carinii sp. f. hominis (P. carinii f.sp. hominis)
      mt large subunit ribosomal RNA site 85 were detected by 2 methods: direct
      sequencing and 3 different allele-specific polymerase chain reaction assays.
      Although limited data on patient contacts were available, the detected P. c.
      hominis genotypes do not support person-to-person transmission as the predominant
      transmission route of P. carinii in humans.

PMID- 11345222
TI  - Soluble adhesion molecules, cytokines and cellular markers in serum in patients
      with acute infections.
AB  - The aim of this study was to evaluate the diagnostic capacity of a number of
      blood components such as soluble adhesion molecules, interleukin-6 (IL-6),
      myeloperoxidase (MPO) and lysozyme in the distinction of acute bacterial and
      viral infections. Blood was taken from 115 acutely infected patients at admission
      before any treatment and in some cases on several consecutive days. 35 of the
      patients had a definite viral cause for their infection and 66 a bacterial cause.
      All variables were raised in patients with acute bacterial infections. Soluble
      vascular cell adhesion molecule-1 (sVCAM-1), sE-selectin, lysozyme and MPO were
      also raised in acute viral infections, but for sE-selectin and MPO less so than
      in bacterial infections. Evaluation of the diagnostic power showed that for MPO
      and IL-6 at cut-offs of 1300 microg/l and 100 ng/l, respectively, the positive
      predictive value was 97% and 100% and the negative predictive value 78% and 76%,
      respectively, in the classification of acute bacterial infections. In the
      distinction between viral or bacterial causes of acute infections in otherwise
      healthy subjects serum measurements of MPO and IL-6 are valuable tools and should
      be considered as diagnostic aids in the routine setting. The soluble adhesion
      molecules did not offer any further information in this respect.

PMID- 11345223
TI  - Comparison of P-triglyceride levels among patients with human immunodeficiency
      virus on randomized treatment with ritonavir, indinavir or ritonavir/saquinavir.
AB  - This study compared the alterations in p-triglyceride (PT) in 111 protease
      inhibitor (PI)-naive patients on randomized treatment with either indinavir (800
      mg 3 times daily), ritonavir (600 mg twice daily) or ritonavir/saquinavir (400 mg
      each twice daily) and 2 nucleoside reverse transcriptase inhibitors (NRTIs). PT
      (non-fasting) was measured at regular intervals until week 48. PT levels were
      evaluated in relation to PI regime, CD4 cell count and prior NRTI experience. The
      effect on PT levels of changing PI regime was analysed. For 24 patients fasting
      and non-fasting PT values were correlated. In the ritonavir-containing arms PT
      levels increased significantly (median PT at baseline: 1.80 mmol/l; week 36: 2.3
      mmol/l; p < 0.001). In the indinavir arm no significant rise in PT levels was
      observed. Comparing the PI arms at week 48 showed significantly higher levels of
      PT in the ritonavir-containing arms than in the indinavir arm (p < 0.001). There
      was a high correlation between fasting and non-fasting PT values (p < 0.001, p =
      0.88). A significant decline in PT values when changing PI treatment was observed
      (n = 13, p = 0.016). Ritonavir-containing regimens caused a rapid and sustained
      elevation of PT values, while indinavir did not significantly affect PT levels.

PMID- 11345224
TI  - Mitral valve endocarditis following balloon mitral valvotomy.
AB  - The case of a patient who developed fungal valve endocarditis due to Candida
      albicans following balloon mitral valvotomy is presented. The patient did not
      have any obvious predisposing factors which led to the development of fungal
      endocarditis.

PMID- 11345225
TI  - A case of intoxication after a bite by Latrodectus tredecimguttatus.
AB  - A case of intoxication in Southern Bulgaria after a bite from the venomous spider
      Latrodectus tredecimguttatus is reported. The development of both local (acute
      pain, itching erythema, paraesthesiae in the area of the bite) and general
      (weakness, headache, dizziness, fever, vomiting, myalgia, muscle cramps)
      symptoms, which passed relatively easily, is described. The clinical picture and
      treatment are briefly commented on.

PMID- 11345226
TI  - Acute Q fever: a cause of fatal hepatitis in an Icelandic traveller.
AB  - Domestic Q fever is rare in the Nordic countries; the infection is acquired
      abroad in the majority of cases. This is the first Nordic report of a fatal case
      of Q fever, which occurred in an Icelandic cancer patient who had travelled to
      the Canary Islands.

PMID- 11345227
TI  - Liposomal amphotericin B and surgery in the successful treatment of invasive
      pulmonary mucormycosis in a patient with acute T-lymphoblastic leukemia.
AB  - Pulmonary mucormycosis is a usually fatal opportunistic infection in
      immunocompromised patients. We describe the first case of an adult patient with
      hematological malignancy and profound neutropenia to survive a disseminated
      pulmonary Rhizomucor pusillus infection. Early diagnostic procedures combined
      with high doses of liposomal amphotericin B and surgical resection may have
      contributed to the successful outcome.

PMID- 11345228
TI  - Role of platelet glycoprotein IIb/IIIa in ADP-activated platelet adhesion to
      aortic endothelial cells in vitro: observation with video-enhanced contrast
      microscopy.
AB  - Intravascular thrombus formation downstream of cerebral arterial occlusion may
      result in necrosis of ischemic tissue. To clarify the causative mechanisms,
      interaction between adenosine-5'-diphosphate (ADP)-activated platelets and
      cultured human aortic endothelial cells (HAEC) was examined by employing video
      enhanced contrast-differential interference contrast (VEC-DIC) microscopy. The
      numbers of (1) control/platelets, (2) ADP-activated platelets, (3) ADP-activated,
      anti-platelet GP Ibalpha antibody (GUR20-5)-treated platelets, and (4) ADP
      activated, platelet GP IIb/IIa antagonist (TAK-029)-treated platelets, associated
      with HAEC after superfusion and wash-out were counted in visual fields of 30 x 30
      microm2. Many ADP-activated platelets adhered to HAEC directly, while almost no
      platelets adhered to HAEC in the control. The adhesion was almost completely
      blocked by the GP IIb/IIIa antagonist, but not by GP Ibalpha antibody. We
      conclude that initial binding of ADP-activated platelets to HAEC is mediated by
      platelet GP IIb/IIIa in this in vitro system.

PMID- 11345229
TI  - Gel-filtration of sickle erythrocytes: separation based on cell deformability.
AB  - Filtration of red blood cells (RBC) through columns of pre-swollen agarose-based
      beads has been evaluated using cells from subjects with sickle cell disease.
      Elution profiles from these gels showed elution times close to normal controls
      for a large fraction of sickle erythrocytes and a prolonged elution time for a
      sub-population of these cells. Analysis of red blood cell deformability using a
      computerized micropore filtration system (CTA) indicated that the deformability
      of sickle red blood cells in the first fraction was similar to controls but that
      the last fraction contained a sub-population of rigid RBC. We thus conclude that
      sickle red blood cell separation in columns of agarose-based beads is based upon
      cell deformability. Gel filtration therefore appears to be an interesting tool
      for the study of red blood cells in a variety of disorders with sub-populations
      of rigid, abnormal cells, and seems especially suited for studies in various
      sickle cell diseases. KEYWORDS: Deformability, gel filtration, sickle cell
      disease, erythrocyte

PMID- 11345230
TI  - The influence of calcium ions and ionophore A23187 on microrheological
      characteristics of erythrocytes by new model ektacytometry.
AB  - After rabbit's erythrocytes were treated with different concentrations of
      intercellular Ca2+ and ionophore A23187 respectively, the orientation index
      (DI)or, and small deformation index (DI)d of rabbit erythrocytes were measured by
      new model ektacytometry. The results demonstrated that (DI)or and (DI)d decreased
      while the concentration of intercellular Ca2+ or ionophore A23187 increased.
      Suggesting that the deformability of erythrocytes was reduced after treatment
      with intercellular Ca2+ or ionophore A23187. Furthermore, the effect of ionophore
      A23187 on the microrheology of erythrocytes is more notable than that of
      intercellular Ca2+.

PMID- 11345231
TI  - Cytosolic calcium and hemorheological patterns during arterial hypertension.
AB  - Hypertension can be considered as a progressive ischaemic syndrome interesting
      micro- and macrovasculature. In hypertensives it is possible to observe a link
      between an increase in peripheral resistance and blood viscosity, and a decrease
      in red blood cell (RBC) deformability. It is important to underline the link
      between the increase of blood viscosity, the decrease of RBC deformability and
      the cytosolic calcium level, which is related to the ischaemic syndrome in
      hypertension. The aim of this study was to evaluate the level of Ca++ and its
      possible correlation with hemorheological patterns during arterial hypertension.
      Two groups were studied: Group 1 consisted of 18 mild hypertensives (11 males and
      7 pre-menopausal females, aged 39 +/- 3 years). This group was of medium risk
      according to WHO and ISH (1999) with no other pathologies apart from peripheral
      occlusive arterial disease II stage type A. Group 2 was made up of 14 healthy
      subjects (9 males and 5 females, aged 34 +/- 4 years). The intraerythrocytic
      cytosolic calcium was evaluated using a fluorescent marker FURA 2/AM
      (Calbiochem). The following hemorheological parameters were also assessed using
      the new Laser assisted Optical Rotational Red Cell Analyzer (LORCA) according to
      the Hardeman method (1994): RBC deformability-Elongation Index (EI), RBC
      aggregability- aggregation half time (t 1/2). The data obtained showed that
      compared to the control group the hypertensives had a significantly higher level
      of intraerythrocytic cytosolic calcium (p < 0.01), plus a significant decrease in
      EI and t 1/2 evaluated using LORCA. We also observed a significant correlation (p
      < 0.01) between an increase in Ca++ and a decrease in EI in the hypertensive
      patients. Moreover our study revealed a significant correlation between the
      increase in intraerythrocytic Ca++ and the t 1/2 decrease. The evaluation of the
      hemorheological patterns and cytosolic calcium could explain the impairment in
      peripheral perfusion and oxygenation in hypertensive patients and could provide a
      good model for a better evaluation and treatment of microvasculature perfusion in
      subjects with essential and complicated hypertension.

PMID- 11345232
TI  - Hemorheological and oxygen free radical associated alterations during and after
      percutaneous transluminal coronary angioplasty.
AB  - Percutaneous transluminal coronary angioplasty (PTCA) is a frequently used method
      in the treatment of coronary artery disease. Coronary stenosis, endothelial
      injury, and ischemia-reperfusion caused by the balloon inflation and deflation
      during this procedure can cause several changes in blood flow. In our study 19
      patients (mean age: 58 +/- 9 years) undergoing PTCA were examined. For the
      laboratory measurements several blood samples were taken from the femoral vein
      and the coronary sinus before and 30 minutes after PTCA, and from the cubital
      vein 1, 2, 5 days and 1, 6 months after PTCA. Among hemorheologic parameters
      hematocrit, plasma fibrinogen level, plasma and whole blood viscosities were
      measured and corrected blood viscosity value was calculated. To characterize the
      oxidative stress, samples were analyzed for thiobarbituric acid reactive
      substances (TBARS) of blood as a marker of lipidperoxidation and changes in the
      antioxidant system were investigated by measuring the activity of superoxide
      dismutase, catalase and the concentration of glutathione; superoxide generating
      capacity of isolated leukocytes and platelet aggregation were examined as markers
      of cellular activation. Plasma fibrinogen concentration increased markedly during
      the first and second day after PTCA (p < 0.001), which was accompanied by the
      elevation of plasma viscosity (p < 0.05). Plasma fibrinogen returned to the
      baseline at the one-month check-up visit, but there was a significant increase in
      its concentration by the end of the sixth month follow-up. Apparent whole blood
      viscosity at 90 s (-1) showed gradually increasing values up to the one- and six
      month check-up visits (p < 0.01), which can partially be explained by the
      elevation of hematocrit. Corrected blood viscosity was significantly elevated on
      the fifth day already (p < 0.01), and one month later also. Superoxide production
      of leukocytes showed an increasing tendency (p = 0.05), and blood TBARS was
      elevated after one day (p < 0.05) and remained higher during the following days.
      Catalase activity showed significantly increasing values (p < 0.01) during the
      hospital phase, then at the end of the first month. SOD activity and spontaneous
      platelet aggregation were higher in the samples from the coronary sinus than in
      those from the peripheral vein before the procedure; 30 minutes after PTCA
      increased levels in the peripheral sample were found (p < 0.01). Our findings
      indicate that PTCA may cause significant changes in the hemorheologic and free
      radical associated parameters, which can affect the final outcome of this
      intervention.

PMID- 11345233
TI  - Erythrocyte deformability and erythrocyte aggregation in preeclampsia.
AB  - One of the features of preeclampsia is impaired blood rheology due to altered
      erythrocyte aggregation and erythrocyte deformability. We investigated these two
      parameters which affect the viscosity of blood, along with serum and
      intraerythrocytic magnesium concentrations, immunoglobulin titres and fibrinogen
      concentration in 12 preeclamptic women. Eighteen (18) other non-preeclamptic,
      gestation-matched women acted as controls. Erythrocyte deformability, expressed
      as elongation index (EI), and erythrocyte aggregation expressed as aggregation
      half-time (t 1/2) were measured with the Laser-assisted Optical Rotational Cell
      Analyser (LORCA). Serum and intraerythrocytic magnesium concentrations were
      analysed by atomic absorption spectrometry, immunoglobulin titres by radial
      immunodiffusion and fibrinogen concentration by a clot weight technique. There
      was no statistically significant difference in these parameters between
      preeclamptics and controls suggesting that erythrocyte deformability and
      aggregation as well as serum and intraerythrocytic concentrations, fibrinogen
      levels and immunoglobulin titres are not altered in preeclampsia. Further
      investigations are required in severe preeclampsia and in preeclamptic women
      taking magnesium sulphate supplement.

PMID- 11345234
TI  - Effects of alprostadil on blood rheology and nucleoside metabolism in patients
      affected with lower limb chronic ischaemia.
AB  - The acute (0.57 microg/kg i.v. in 2 hours) and long-term (0.57 microg/kg i.v. in
      2 hours for 5 days over 4 weeks) effects of the PGE1 analogue alprostadil were
      studied in patients affected with intermittent claudication. Whole Blood
      Viscosity (WBV), Whole Blood Filterability (WBF), haematocrit (Htc) and
      fibrinogen plasma concentration, were studied together with P50, 2,3
      diphosphoglycerate, and adenosine plasma levels. Moreover, in the long-term
      study, pain-free (PFWD) and maximal walking distance (MWD) were measured. Single
      alprostadil infusion induced an improvement in WBV, WBF, and oxygen transport,
      and an increase in adenosine plasma levels. Long-term alprostadil administration
      produced a decrease in WBV only, without significant changes in WBF, Htc,
      fibrinogen, P50, 2,3-diphosphoglycerate, also inducing a significant prolongation
      of PFWD and MWD. The possibility is suggested that pulse rises in adenosine
      plasma levels play a role in the effects of chronic alprostadil administration,
      maybe in a way similar to that observed in the phenomenon of ischaemic
      preconditioning,

PMID- 11345235
TI  - Hemorheological alterations in patients with diabetic retinopathy.
AB  - Hemorheological factors play an important role in the pathogenesis of different
      cardiovascular diseases. Diabetes mellitus resulting in micro- and
      macroangiopathies is one of the major risk factors for cardiovascular diseases.
      In our present study the hemorheological parameters (hematocrit, plasma
      fibrinogen level, plasma and whole blood viscosity, red blood cell aggregation)
      of 30 diabetic patients (mean age: 57 +/- 12 years) and 30 healthy volunteers
      (mean age: 31 +/- 10 years) were examined. The fundus appearance of patients
      showed diabetic retinopathy; non-proliferative stage in 22 cases,
      preproliferative or proliferative stage in 8 cases. The measured hemorheological
      parameters of the examined patients were in the pathological range and were
      significantly higher than those of healthy volunteers (hematocrit: p < 0.01;
      plasma fibrinogen: p < 0.001; plasma viscosity: p < 0.01; whole blood viscosity:
      p < 0.001; red blood cell aggregation: p < 0.01). In our study there was not
      significant difference in the hemorheologic variables of patients with different
      stages of retinopathy. Our results propose the importance of hemorheologic
      factors in the development of diabetic microangiopathy.

PMID- 11345236
TI  - Membranous glomerulopathy: emphasis on secondary forms and disease variants.
AB  - Membranous glomerulopathy (MGN) is characterized by subepithelial immune complex
      deposits and glomerular basement membrane (GBM) thickening. The majority of
      patients present with nephrotic syndrome and outcomes are variable.
      Pathologically, deposits at sites other than the subepithelial aspect of the GBM
      favor the presence of secondary forms of MGN which are seen most commonly in the
      setting of autoimmune disease, infection, neoplasia, and with certain therapeutic
      agents. MGN is the most common form of de novo glomerular disease seen in the
      renal allograft and may be seen concurrently with other forms of glomerular
      disease including focal segmental glomerulosclerosis, IgA nephropathy, diabetic
      nephropathy, and anti-TBM nephritis. This review emphasizes the detection of
      secondary forms and variants of MGN.

PMID- 11345237
TI  - Benign fibro-osseous lesions: a review of current concepts.
AB  - The benign fibro-osseous lesions (BFOL) represent a clinically diverse group of
      disorders of bone that share similar histopathologic features. As a group, they
      are relatively common in the craniofacial complex, especially the jaws. Although
      the general concept of BFOL is relatively well known, specific diagnostic
      interpretation of individual cases is often challenging. New concepts and
      controversies have arisen over the past 10 to 15 years regarding classification
      and diagnostic criteria. However, among the new theories and contentions, there
      is now essential agreement that the osseous dysplasias represent a single disease
      process, while the so-called "juvenile active ossifying fibroma" and other
      "aggressive," "active," "psammomatoid" ossifying/cementifying fibromas remain
      controversial. This review is presented to update the surgical pathologist on the
      various entities comprising the spectrum of BFOL and to examine the criteria for
      their diagnosis.

PMID- 11345238
TI  - Pancreatic acinar cell carcinoma.
AB  - Acinar cell carcinomas (ACCs) are rare neoplasms that represent less than 2% of
      all exocrine tumors of the pancreas. Although they occur more often in adults
      between the 5th and 7th decades of life, a few cases have been reported in
      children. Histologically, ACCs can resemble islet cell tumors, but they differ in
      their ultrastructural and immunohistochemical features. Although ACCs present a
      bland histology, they are highly malignant and the survival of patients with
      these tumors, even though better than that of those with ductal cell carcinomas,
      is generally poor.

PMID- 11345239
TI  - HPV testing is not useful for LSIL Triage--but stay tuned.

PMID- 11345240
TI  - Loss of E-cadherin is the fundamental defect in diffuse-type gastric carcinoma
      and infiltrating lobular carcinoma of the breast.

PMID- 11345241
TI  - Selected case from the Arkadi M. Rywlin International Pathology Slide Seminar:
      hyaline fibromatosis.

PMID- 11345242
TI  - The unidentified diffuse interstellar bands as evidence for large organic
      molecules in the interstellar medium.
AB  - Since 1921, astronomers have been aware of a set of spectral absorption features
      that are formed in interstellar space but are not identifiable with any known
      atomic or molecular species. Today some 200 of these so-called diffuse
      interstellar bands (DIBs) are known, yet none has yet been identified
      unambiguously with any specific carrier. Recent evidence from astronomical
      observations, laboratory spectroscopy, and chemical studies suggests that the
      responsible species are large carbon-bearing molecules. This paper provides a
      brief history of the DIB problem, a review of suggested carriers, and a
      description and discussion of new results from the telescope and from laboratory
      measurements of chemical reaction rates in candidate carriers.

PMID- 11345243
TI  - Aromatic hydrocarbons, diamonds, and fullerenes in interstellar space: puzzles to
      be solved by laboratory and theoretical astrochemistry.
AB  - New research is presented, and previous research is reviewed, on the emission and
      absorption of interstellar aromatic hydrocarbons. Emission from aromatic
      hydrocarbons dominates the mid-infrared emission of many galaxies, including our
      own Milky Way galaxy. Only recently have aromatic hydrocarbons been observed in
      absorption in the interstellar medium, along lines of sight with high column
      densities of interstellar gas and dust. Much work on interstellar aromatics has
      been carried out, with astronomical observations and laboratory and theoretical
      astrochemistry. In many cases, the predictions of laboratory and theoretical work
      are confirmed by astronomical observations but, in other cases, clear
      discrepancies exist that provide problems to be solved by a combination of
      astronomical observations, laboratory studies, and theoretical studies. The
      emphasis of this paper will be on current outstanding puzzles concerning aromatic
      hydrocarbons that require further laboratory and theoretical astrochemistry to
      resolve. This paper will also touch on related topics where laboratory and
      theoretical astrochemistry studies are needed to explain astrophysical
      observations, such as a possible absorption feature due to interstellar
      'diamonds' and the search for fullerenes in space.

PMID- 11345244
TI  - Searches for new interstellar molecules, including a tentative detection of
      aziridine and a possible detection of propenal.
AB  - Rotational spectroscopy at millimeter wavelengths is a powerful means of
      investigating the chemistry of dense interstellar clouds. These regions can
      exhibit an interesting complement of gas phase molecules, including relatively
      complex organics. Here we report the tentative first astronomical detection of
      aziridine (ethylenimine), the possible detection of propenal (acrolein), and
      upper limits on the abundances of cyclopropenone, furan, hydroxyethanal
      (glycolaldehyde), thiohydroxylamine (NH2SH), and ethenol (vinyl alcohol) in
      various interstellar clouds.

PMID- 11345245
TI  - Spectroscopy of H3+ and its impact on astrophysics.
AB  - Since the original laboratory detection of an H3+ spectrum 20 years ago, the
      search has been on for astronomical observations of this important and
      fundamental molecular ion. Successful detection of H3+ in gas-giant planets,
      supernova ejecta and the interstellar medium as well as the prospects for future
      observations are discussed. The role H3+ has in determining the atmospheric
      structure of both the gas giants and cool metal-free planets is explored.

PMID- 11345246
TI  - Interstellar matrices: the chemical composition and evolution of interstellar
      ices as observed by ISO.
AB  - Matrix isolation techniques have been developed in the early sixties as a tool
      for studying the spectroscopic properties of out of equilibrium species (atoms,
      radicals, ions, reactive molecules), embedded in rare gas inert matrices at low
      temperatures. Cold interstellar grains surfaces are able to condense out gas
      phase molecules, routinely observed by radioastronomy. These grain 'mantles' can
      be considered as 'interstellar matrices'. However, these matrices are not clean
      and unreactive. They are made principally of dirty ices whose composition must be
      determined carefully to assess the importance of the solid state chemistry that
      takes place in the Interstellar Medium. Infrared spectroscopy, both in astronomy
      and in the laboratory, is the unique tool to determine the chemical composition
      of these ices. Astronomical spectra can directly be compared with laboratory ones
      obtained using classical matrix isolation techniques. Furthermore, dedicated
      experiments may be undertaken to further improve the understanding of the basic
      physico-chemical processes that take place in cosmic ices.

PMID- 11345247
TI  - Spectroscopic diagnostics of organic chemistry in the protostellar environment.
AB  - A combination of astronomical observations, laboratory studies, and theoretical
      modelling is necessary to determine the organic chemistry of dense molecular
      clouds. We present spectroscopic evidence for the composition and evolution of
      organic molecules in protostellar environments. The principal reaction pathways
      to complex molecule formation by catalysis on dust grains and by reactions in the
      interstellar gas are described. Protostellar cores, where warming of dust has
      induced evaporation of icy grain mantles, are excellent sites in which to study
      the interaction between gas phase and grain-surface chemistries. We investigate
      the link between organics that are observed as direct products of grain surface
      reactions and those which are formed by secondary gas phase reactions of
      evaporated surface products. Theory predicts observable correlations between
      specific interstellar molecules, and also which new organics are viable for
      detection. We discuss recent infrared observations obtained with the Infrared
      Space Observatory, laboratory studies of organic molecules, theories of molecule
      formation, and summarise recent radioastronomical searches for various complex
      molecules such as ethers, azaheterocyclic compounds, and amino acids.

PMID- 11345248
TI  - Millimeter-wave time-resolved studies of HCO+-H2 inelastic collisions.
AB  - A novel ion cell has been constructed for the purpose of studying rotationally
      inelastic collisions involving truly thermal molecular ions at low temperatures.
      With this ion cell, time-resolved double resonance (pump-probe) spectroscopic
      experiments have been performed to determine the cross sections for relaxation of
      the J = 2 state of HCO+ in collisions with normal-H2 at temperatures around 40
      and 77 K. The HCO+ is pumped through the J = 2<--1 transition and probed via the
      J = 3<--2 transition. The cross sections at the lower temperature are slightly
      below those predicted by the simple Langevin theory, while those at the higher
      temperature are in good agreement with this theory.

PMID- 11345249
TI  - Vibrational spectroscopy of gas-phase neutral and cationic phenanthrene in their
      electronic groundstates.
AB  - Various experimental methods are applied to retrieve the vibrational structure of
      phenanthrene in its neutral and cationic groundstates. The linear infrared (IR)
      absorption spectra in the 400-1650 cm(-1) range of jet-cooled phenanthrene and
      its cation, both clustered with either an argon or a neon atom, are obtained via
      photo-induced cluster dissociation spectroscopy. The spectra observed are in good
      agreement with calculated spectra of the bare species. However, the observed
      spectrum of cationic phenanthrene shows more lines and lines with different
      intensities in the 900-1400 cm(-1) range than expected from calculations.
      Additional spectra of the perdeuterated phenanthrene Ar cation, and the warm (T
      approximately > room temperature) bare phenanthrene cation are recorded. Also the
      mass-analyzed threshold ionization spectra of bare phenanthrene and phenanthrene
      Ar are recorded and compared with each other. Comparison of the spectral data
      recorded to calculated spectra of bare neutral, cationic and cationic
      perdeuterated phenanthrene, as well as to IR spectra recorded in matrix-isolation
      experiments, explicitly demonstrates that cluster dissociation spectroscopy is a
      valid and powerful method to obtain IR spectroscopic information of bare neutral
      and cationic jet-cooled poly-aromatic hydrocarbons.

PMID- 11345250
TI  - Hydrogenation of polycyclic aromatic hydrocarbons as a factor affecting the
      cosmic 6.2 micron emission band.
AB  - While many of the characteristics of the cosmic unidentified infrared (UIR)
      emission bands observed for interstellar and circumstellar sources within the
      Milky Way and other galaxies, can be best attributed to vibrational modes of the
      variants of the molecular family known as polycyclic aromatic hydrocarbons (PAH),
      there are open questions that need to be resolved. Among them is the observed
      strength of the 6.2 micron (1600 cm(-1)) band relative to other strong bands, and
      the generally low strength for measurements in the laboratory of the 1600 cm(-1)
      skeletal vibration band of many specific neutral PAH molecules. Also, experiments
      involving laser excitation of some gas phase neutral PAH species while producing
      long lifetime state emission in the 3.3 micron (3000 cm(-1)) spectral region, do
      not result in significant 6.2 micron (1600 cm(-1)) emission. A potentially
      important variant of the neutral PAH species, namely hydrogenated-PAH (H(N)-PAH)
      which exhibit intriguing spectral correlation with interstellar and circumstellar
      infrared emission and the 2175 A extinction feature, may be a factor affecting
      the strength of 6.2 micron emission. These species are hybrids of aromatic and
      cycloalkane structures. Laboratory infrared absorption spectroscopy augmented by
      density function theory (DFT) computations of selected partially hydrogenated-PAH
      molecules, demonstrates enhanced 6.2 micron (1600 cm(-1)) region skeletal
      vibration mode strength for these molecules relative to the normal PAH form. This
      along with other factors such as ionization or the incorporation of nitrogen or
      oxygen atoms could be a reason for the strength of the cosmic 6.2 micron (1600
      cm(-1)) feature.

PMID- 11345251
TI  - Laboratory spectra of cold gas phase polycyclic aromatic hydrocarbon cations, and
      their possible relation to the diffuse interstellar bands.
AB  - A novel laboratory technique is described, combining the use of supersonic
      expansion, laser excitation and small aromatic-rare gas van der Waals (vdW)
      clusters properties, which was developed to access the electronic absorption
      spectra of the polycyclic aromatic hydrocarbon (PAH) cations in the visible. It
      consists in preparing vdW complexes of the PAH molecule with a rare gas in a
      molecular beam, to photoionize it by resonant selective two-photon ionization,
      then to photodissociate this ionic complex by means of a delayed laser pulse in a
      time-of-flight mass spectrometer. The method is illustrated by presenting the
      visible spectra of the Naphthalene, Phenanthrene, Fluorene and Phenylacetylene
      cations. Such spectra can be unambiguously compared to the astronomical spectra
      of reddened stars, which exhibit the so-called diffuse interstellar bands (DIBs)
      in absorption. An interesting feature of the technique is its ability to measure
      the absolute absorption cross-sections. The large values of the oscillator
      strengths of the transitions, which are derived, are discussed in the
      astrophysical context which consists in considering that the PAH cations could be
      carriers for some of the DIBs.

PMID- 11345252
TI  - Carbon chains and rings in the laboratory and in space.
AB  - Seventy-seven reactive organic molecules of astrophysical interest have been
      identified in a supersonic molecular beam, 73 in the radio band by Fourier
      transform microwave spectroscopy, four in the optical by laser cavity ringdown
      spectroscopy. Most are linear carbon chains, but six consist of carbon chains
      attached to the compact, highly polar C3 ring, and two are rhomboidal cyclic
      configurations of SiC3. The laboratory astrophysics of the radio molecules is
      complete for the time being, in the sense that essentially all the rotational
      transitions of current interest to radio astronomy (including hyperfine structure
      when present) can now be calculated to a small fraction of 1 km s(-1) in
      equivalent radial velocity; six of the radio molecules have already been detected
      in space on the basis of the present data. The FTM spectrometer employed in this
      work is far from fundamental limits of sensitivity, so many more molecules can
      probably be found by refinements of present techniques. The density of reactive
      molecules in our supersonic beam is generally high by the standards of laser
      spectroscopy, and many of the radio molecules probably have detectable optical
      transitions which we are attempting to find, largely motivated by the long
      standing problem of the diffuse interstellar bands. Our most interesting result
      to date is the detection of a fairly strong molecular band at 443 nm in a benzene
      discharge, in exact coincidence with the strongest and best known interstellar
      band. Isotopic shifts measured with partially and totally deuterated benzene
      suggest that the carrier of the laboratory band is a hydrocarbon molecule with
      the elemental formula CnH5, with n most likely in the range 3-6.

PMID- 11345253
TI  - Electronic absorption and resonance Raman spectra of large linear carbon clusters
      isolated in solid argon.
AB  - Neutral and anionic carbon clusters have been generated via a laser-induced
      graphite-based plasma and deposited in a solid argon matrix. Anionic clusters
      were formed from neutral clusters by using crossed electron/carbon cluster beams.
      Thermal annealing (to 36 K) resulted in the aggregation of the smaller carbon
      species, leading to the formation of long chain neutral and anionic clusters.
      Spectroscopic measurements in the ultraviolet, visible, near-infrared and
      infrared regions revealed a series of bands attributable to a homologous set of
      odd-numbered C5-C29 neutral clusters and even-numbered C6(-)-C36- anionic
      clusters. Good agreement is found for the band positions of carbon chains
      containing odd C15-C21 neutrals and even C6(-)-C22- anions, with species
      previously identified by Maier and coworkers using mass selection or laser
      vaporization, followed by neon matrix isolation. Resonance Raman frequencies for
      the neutral C17, C21 and C23 species are shown to be consistent with the above
      attributions. Density functional theory calculations agree well with the observed
      bands. It is found that certain low frequency Raman stretching frequencies
      decrease in a predictable way with increasing chain length. Comparison of the
      0(0)0 absorption transitions of the even C18(-)-C36- anionic clusters with the
      'unidentified' infrared (UIR) interstellar emission bands suggests that the
      electronic emission from specific long chain carbon anions may contribute to the
      some of the UIR bands.

PMID- 11345254
TI  - Carbon and silicate grains in the laboratory as analogues of cosmic dust.
AB  - Carbon and silicate grains are the two main components of cosmic dust. There is
      increasing spectroscopic evidence that their composition varies according to the
      cosmic environment and the experienced processing. Irradiation from ultraviolet
      photons and cosmic rays, as well as chemical interactions with the interstellar
      gas play a crucial role for grain transformation. The study of 'laboratory
      analogues' represents a powerful tool to better understand the nature and
      evolution of cosmic materials. In particular, simulations of grain processing are
      fundamental to outline an evolutionary pathway for interstellar particles. In the
      present work, we discuss the ultraviolet and infrared spectral changes induced by
      thermal annealing, ultraviolet irradiation, ion irradiation and hydrogen atom
      bombardment in carbon and silicate analogue materials. The laboratory results
      give the opportunity to shed light on the long-standing problems of the
      attribution of ultraviolet and infrared interstellar spectral features.

PMID- 11345255
TI  - Optical properties of synthetic carbon nanoparticles as model of cosmic dust.
AB  - Carbon nanoparticles synthesised by laser pyrolysis of small hydrocarbons are
      deposited at low energy on a silicon substrate. Infrared spectroscopy of the as
      formed films are studied as a function of the synthesis parameters and post
      treatments, such as annealing and heavy ion irradiation. Correlation between
      infrared spectroscopy and multiscale organisation of the samples is made through
      transmission electron microscopy, including image analysis. Changes in infrared
      spectra are analysed in terms of the carbon network building. The relevance of
      the results to model the structure and spectroscopy of carbon dust in the carbon
      rich circumstellar media is discussed.

PMID- 11345256
TI  - Formation and spectroscopy of carbides.
AB  - We review the evidence for carbides in space both from infrared spectroscopy and
      direct measurements on presolar grains extracted from primitive meteorites. The
      paper includes a discussion of the structural properties of silicon carbide and
      metal carbides and their formation routes from the gas phase. In addition, we
      present spectroscopic data in the infrared, which are required for a better
      understanding of astronomical spectra.

PMID- 11345257
TI  - Vibrational spectroscopy of ion-irradiated ices.
AB  - In the last 20 years we have studied some effects induced by fast ions (E
      approximately keV-MeV) impinging on solid materials (mainly ices) with a view to
      their astrophysical relevance. The main techniques used have been infrared and
      Raman spectroscopy. Here we review some of the results obtained so far
      concerning, in particular, the formation of new species not present in the
      original sample. When hydrocarbons are an important constituent of the target ion
      irradiation gives rise also to a refractory residue which is left over after
      warming up. In addition we present some preliminary results of a new study, still
      in progress, on the infrared properties of the organic residue formed after
      irradiation of an icy mixture with H-, C-, N- and O-bearing species. Furthermore
      we present the micro-Raman spectra of some fragments of Orgueil a carbonaceous
      chondrite meteorite. Some astrophysical applications of these laboratory results
      are also discussed.

PMID- 11345258
TI  - Mid- and far-infrared spectroscopic studies of the influence of temperature,
      ultraviolet photolysis and ion irradiation on cosmic-type ices.
AB  - Infrared (IR) studies of laboratory ices can provide information on the evolution
      of cosmic-type ices as a function of different simulated space environments
      involving thermal, ultraviolet (UV), or ion processing. Laboratory radiation
      experiments can lead to the formation of complex organic molecules. However,
      because of our lack of knowledge about UV photon and ion fluxes, and exposure
      lifetimes, it is not certain how well our simulations represent space conditions.
      Appropriate laboratory experiments are also limited by the absence of knowledge
      about the composition, density, and temperature of ices in different regions of
      space. Our current understanding of expected doses due to UV photons and cosmic
      rays is summarized here, along with an inventory of condensed-phase molecules
      identified on outer solar system surfaces, comets and interstellar grains. Far-IR
      spectra of thermally cycled H2O are discussed since these results reflect the
      dramatic difference between the amorphous and crystalline phases of H2O ice, the
      most dominant condensed-phase molecule in cosmic ices. A comparison of mid-IR
      spectra of products in proton-irradiated and UV-photolyzed ices shows that few
      differences are observed for these two forms of processing for the simple binary
      mixtures studied to date. IR identification of radiation products and experiments
      to determine production rates of new molecules in ices during processing are
      discussed. A new technique for measuring intrinsic IR band strengths of several
      unstable molecules is presented. An example of our laboratory results applied to
      Europa observations is included.

PMID- 11345259
TI  - Looking for the PC bond in space: HPCO and HPCS as possible tracers.
AB  - This paper looks at the possibility of astronomical detection of molecules of
      prebiotic interest containing phosphorus. Attention has been focused on the most
      stable species that can be formed with the four [C,H,O,P] atoms. Ab initio
      coupled cluster molecular orbital methods and density functional theory have been
      used. It is found that the best candidate for detection is singlet HPCO
      (corresponding to singlet HNCO), which lies 23.5 kcal/mol lower than the next
      isomer (HOCP) and has a non-negligible dipole moment of 0.8 D. Theoretical
      rotational constants and infrared (IR) spectra have been determined for HPCO and
      the closely related HPCS. By correcting the known inadequacies in the
      calculations with the average theoretical to experimental ratio from two
      benchmark molecules (HOCO+ and HNCO), it is possible to obtain rotational
      constants and IR frequencies of considerably higher accuracy. The corrected
      values of B = 5.5322 GHz and C = 5.4071 GHz for HPCO, and B = 3.0416 GHz and C =
      3.0014 GHz for HPCS should be accurate to within a few tenths of a percent. It
      can also be predicted that only the 2000 cm(-1) (HPCO) and 1400 cm(-1) (HPCS) IR
      bands have sufficient intensity to be searched in the low-abundance conditions
      prevailing in space.

PMID- 11345260
TI  - A fully ab initio potential curve of near-spectroscopic quality for OH- ion:
      importance of connected quadruple excitations and scalar relativistic effects.
AB  - A benchmark study has been carried out on the ground-state potential curve of the
      hydroxyl anion, OH-, including detailed calibration of both the l-particle and n
      particle basis sets. The CCSD(T) basis set limit overestimates omega(e) by about
      10 cm(-1), which is only remedied by inclusion of connected quadruple excitations
      in the coupled cluster expansion--or, equivalently, the inclusion of the 2pi
      orbitals in the active space of a multireference calculation. Upon inclusion of
      scalar relativistic effects (-3 cm(-1) on omega(e)), a potential curve of
      spectroscopic quality (sub-cm(-1) accuracy) is obtained. Our best computed
      EA(OH), 1.828 eV, agrees to three decimal places with the best available
      experimental value. Our best computed dissociation energies, D0(OH-) = 4.7796 eV
      and D0(OH) = 4.4124 eV, suggest that the experimental D0(OH) = 4.392 eV may
      possibly be about 0.02 eV too low.

PMID- 11345261
TI  - Vibrational energy levels for CH4 from an ab initio potential.
AB  - Many areas of astronomy and astrophysics require an accurate high temperature
      spectrum of methane (CH4). The goal of the present research is to determine an
      accurate ab initio potential energy surface (PES) for CH4. As a first step
      towards this goal, we have determined a PES including up to octic terms. We
      compare our results with experiment and to a PES based on a quartic expansion.
      Our octic PES gives good agreement with experiment for all levels, while the
      quartic PES only for the lower levels.

PMID- 11345262
TI  - Ab initio calculations of electronically excited states of cyano-substituted
      polyacetylene cations.
AB  - The transition energies for the lowest energy pi --> pi* electronic excitations
      are calculated with the complete active space self-consistent field method
      (CASSCF) and with the complete active space second-order perturbation theory
      method (CASPT2) for the linear cyano-substituted polyacetylene cations, H-Cn-CN+,
      n = 4-11, and NC-Cn-CN+, n = 2-10. These systems are models for an important
      class of interstellar species. We demonstrate the utility of the theoretical
      calculations in assigning the experimental spectra.

PMID- 11345263
TI  - Closed-shell polycyclic aromatic hydrocarbon cations: a new category of
      interstellar polycyclic aromatic hydrocarbons.
AB  - Density functional theory has been employed to calculate the harmonic frequencies
      and intensities of a range of polycyclic aromatic hydrocarbon (PAH) cations that
      explore both size and electronic structure effects on the infrared spectroscopic
      properties of these species. The sample extends the size range of PAH species
      considered to more than 50 carbon atoms and includes several representatives from
      each of two heretofore unexplored categories of PAH cations: (1) fully benzenoid
      PAH cations whose carbon skeleton is composed of an odd number of carbon atoms
      (C(odd) PAHs); and (2) protonated PAH cations (HPAH+). Unlike the radical
      electronic structures of the PAH cations that have been the subject of previous
      theoretical and experimental work, the species in these two classes have a
      'closed'-shell electronic configuration. The calculated spectra of
      circumcoronene, C54H18, in both neutral and (radical) cationic form are also
      reported and compared with those of the other species. Overall, the C(odd) PAHs
      spectra are dominated by strong CC stretching modes near 1600 cm(-1) and display
      spectra that are remarkably insensitive to molecular size. The HPAH+ species
      evince a more complex spectrum consistent with the added contributions of
      aliphatic modes and their generally lower symmetry. Finally, for both classes of
      closed-shell cations, the intensity of the aromatic CH stretching modes is found
      to increase with molecular size far out of proportion with the number of CH
      groups, approaching a value more typical of neutral PAHs for the largest species
      studied.

PMID- 11345264
TI  - Electronic spectra and ionization potentials of a stable class of closed shell
      polycyclic aromatic hydrocarbon cations.
AB  - Due to their stability, closed shell polycyclic aromatic hydrocarbon (PAH)
      cations are possible candidates as carriers for some of the diffuse interstellar
      bands (DIBs). The electronic absorption spectra and ionization potentials of
      several closed shell PAH cations are determined in this study. We use density
      functional theory (DFT) at the BLYP/6-31G* level to determine the ionization
      potentials and thus confirm the stability of the PAH cations of interest. We use
      time-dependent density functional theory (TDDFT), again at the BLYP/6-31G* level,
      to calculate the vertical excitation energies and oscillator strengths of the PAH
      cations. We observe dominant single absorptions within the DIB spectral region of
      interest in all of the PAH cation spectra except for the smallest member of the
      series.

PMID- 11345265
TI  - Numerical simulation of the infrared emission of interstellar dust.
AB  - The emission of the unidentified infrared bands (UIBs) has been attributed to
      excitation of polycyclic aromatic hydrocarbons (PAHs) by absorption of single
      energetic photons. Williams and Leone (1995) showed experimentally that a
      molecule (naphtalene) is considerably perturbed in this process so that the usual
      simplifying (harmonic) assumptions and associated analytical treatment do not
      apply. On the other hand, the single photon mechanism cannot operate in the
      frequently encountered environments where the radiation field is not strong, or
      the UV photons not hard, enough. This paper explores the 'feasibility' of a
      chemiluminescent process instead, in such cases. In both photonic and chemical
      excitation, the problem of energy redistribution is better tackled numerically.
      Here, a state-of-the-art numerical code is used to simulate naphtalene, a
      hydrocarbon particle of 18 atoms (assumed for the present purposes to be roughly
      representative of the real carrier material) and its chemical reaction with an H
      atom, a species known to be most abundant everywhere in space. The chemical
      energy deposited thus excites the particle into a complicated state of vibration.
      The code thereupon follows the dynamics of all the atoms and calculates the
      electric charge distribution at every step, from which the electric dipole moment
      is derived as a function of time. The FFT of this finally gives the spectral
      density of vibrational energy, which is found to be very different from the
      absorption spectrum of the same particle and to consist of several bands of
      different and varying widths. This--one of our main results--is the evidence of
      mode interactions due to mode anharmonicity and coupling. The energetic
      efficiency of this emission process is high and was proven to be adequate for
      astrophysical purposes. Other properties of this mechanism are also shown to be
      in agreement with observations. The assumptions and weaknesses of the present
      theoretical and numerical treatments are discussed with a view to further
      research.

PMID- 11345266
TI  - Beyond "radiologic-pathologic correlation".

PMID- 11345267
TI  - BaSO4-loaded agarose: a construction material for multimodality imaging phantoms.
AB  - RATIONALE AND OBJECTIVES: Phantom studies are an important part of the evaluation
      of imaging techniques; however, presently available phantom construction
      materials are not adequate for studies involving both magnetic resonance (MR)
      imaging and computed tomography (CT). The purpose of this study was to design a
      phantom construction material useful for multimodality imaging experiments.
      MATERIALS AND METHODS: Iodinated contrast agent or BaSO4 was added during the
      formation of agarose gels. Both CT and MR imaging were performed, and T1 and T2
      values and CT numbers (in Hounsfield units) were obtained for multiple
      combinations of contrast material and agarose. Results. The T2 values of agarose
      gels span the range of those values found in biologic tissues. Phantoms
      containing iodinated contrast agent were not stable; contrast agent diffused
      across concentration gradients. BaSO4-loaded agarose phantoms were stable,
      however, and varying barium concentrations produced phantoms that spanned the
      range of CT numbers found in biologic tissues. Addition of BaSO4 did not
      substantially alter T1 or T2 values of agarose gels. Agarose concentration had
      only a small effect on the CT numbers of BaSO4 suspensions. CONCLUSION: BaSO4
      loaded agarose is an effective material for construction of multimodality imaging
      phantoms. It provides adequate signal intensity for MR imaging and attenuation
      for CT, with independently variable contrast in both modalities.

PMID- 11345269
TI  - A screening method for knee trauma.
AB  - RATIONALE AND OBJECTIVES: The authors performed this study to evaluate whether
      any one conventional radiographic view is sufficient as a screening method in the
      detection of acute knee trauma. MATERIALS AND METHODS: The authors prospectively
      assessed the efficacy of a single conventional radiograph of the knee in the
      detection of signs of knee fractures in 214 consecutive adults with acute knee
      trauma. The evaluated efficacy parameters included specificity, sensitivity,
      negative predictive value (NPV), and positive predictive value. The percentage
      reduction in the need for additional conventional radiographs was also
      calculated. RESULTS: Fifty-three of the 214 patients (24.8%) had a knee fracture.
      The sensitivity of the single lateral view in the detection of knee fractures was
      100% (95% confidence interval [CI] = 94.3, 100). The lateral view of the
      traumatized knee was normal in 143 patients (66.8%). The probability of not
      having a fracture if the lateral view was normal (NPV) was also 100% (95% CI =
      97.9, 100). The need for additional radiographs was reduced 67%. CONCLUSION: A
      single lateral view as a screening tool for knee fractures has a very high
      sensitivity and NPV. Because more than 65% of the patients had a normal lateral
      view in this study, there can be a considerable amount of savings in terms of
      radiology services for these patients.

PMID- 11345268
TI  - Correlation of microvascular permeability derived from dynamic contrast-enhanced
      MR imaging with histologic grade and tumor labeling index: a study in human brain
      tumors.
AB  - RATIONALE AND OBJECTIVES: Dynamic contrast material-enhanced magnetic resonance
      (MR) imaging may be used to quantify fractional blood volume (fBV) and
      microvascular permeability in human brain tumors. Hypothesis is that these
      measurements correlate with tumor histologic grade and immunohistologically
      assessed mitotic activity. MATERIALS AND METHODS: Thirty-eight patients with
      newly diagnosed gliomas underwent MR imaging consisting of dynamic three
      dimensional spoiled gradient-recalled acquisition in the steady state image sets
      following bolus injections of a single dose of gadodiamide. Signal intensity
      changes in blood and tissue were kinetically analyzed, yielding estimates of fBV
      and microvascular permeability (k). Tumor specimens were graded with the World
      Health Organization-II four-point grading score. MIB-1 immunohistochemical
      labeling (anti-Ki-67 monoclonal antibody) was performed in 22 patients to
      evaluate mitotic activity. RESULTS: Histologic study revealed nine grade 2, 14
      grade 3, and 15 grade 4 tumors. fBV ranged from 0.4% to 24%, k from -0.4 to 31.4
      mL/100 cm3 x min, and MIB-1 labeling indexes from 1.7% to 42.8%. Correlation to
      the tumor grade was highest for permeability (r = 0.73), followed by the MIB-1
      index (r = 0.63), and fBV (r = 0.48). Correlation between k and MIB-1 index was
      strong (r = 0.84). There was no statistically significant difference between the
      fBV of any of the groups. Despite some overlap between the permeability values of
      specific tumors from different grades, differences were statistically
      significant. The MIB-1 index was significantly different between grades 3 and 4
      but not between grades 2 and 3. CONCLUSION: Dynamic contrast-enhanced MR imaging
      allows noninvasive determination of tumor fBV and microvascular permeability k. k
      is more reliable than the MIB-1 labeling index for differentiating grade 2 from
      grade 3 tumors.

PMID- 11345270
TI  - Effect of radiologic contrast media on cell volume regulation in rabbit proximal
      renal tubules.
AB  - RATIONALE AND OBJECTIVES: Most radiographic contrast media are hyperosmotic and
      able to shrink cells with which they are in contact. The authors studied cell
      volume control in rabbit proximal renal tubules after incubation with three
      contrast media: iohexol, ioxaglate, and iodixanol. MATERIALS AND METHODS:
      Proximal renal tubules were isolated from rabbit kidneys. The tubules were
      exposed to Ringer solutions containing 5% vol/vol iohexol (final osmolality, 330
      mOsm), ioxaglate (323 mOsm), iodixanol (305 mOsm), or mannitol (control solutions
      with identical osmolalities), and tubule volumes were monitored. After 2 hours of
      incubation, the tubules were stimulated with a hyposmotic Ringer solution (165
      mOsm). Three groups of 10 experiments were performed. RESULTS: All solutions
      induced cell shrinkage (8.3%+/-3.8 [standard error] to 15.4%+/-0.5), which was
      completely or partly reversible in most experiments (volume increase, 44.8%+/
      14.7 to 149.9%+/-107.3) but not those with iohexol and iodixanol. With exposure
      to the hyposmotic solution, the cells swelled by 11.0%+/-1.8 to 39.7%+/-4.8. In
      general, the tubules that had been exposed to the most hyperosmotic solution
      swelled the most. Those exposed to contrast media showed less swelling than the
      mannitol-exposed controls. In all control experiments, the cells exhibited a
      gradual shrinkage (43.6%+/-28.5 to 87.0%+/-13). This regulatory response was
      partly inhibited in tubules exposed to iohexol (39.9%+/-15.8 shrinkage) or
      iodixanol (8.9%+/-15.8) and completely inhibited in those exposed to ioxaglate.
      Iohexol and ioxaglate exposure also led to a decrease in water permeability.
      CONCLUSION: Exposure to hyperosmotic contrast medium tends to induce prolonged
      cell shrinkage, decrease the water permeability of the cellular plasma membranes,
      and compromise the ability to regulate cellular volume. These changes seem to
      reflect both the hyperosmolality of the solutions and their inherent chemical
      properties.

PMID- 11345271
TI  - Brain MR imaging in the evaluation of chronic headache in patients without other
      neurologic symptoms.
AB  - RATIONALE AND OBJECTIVES: The authors investigated the use of magnetic resonance
      (MR) imaging of the brain in adult patients with a primary complaint of chronic
      headache and no other neurologic symptoms or findings and determined the yield
      and MR predictors of major abnormalities in these patients. MATERIALS AND
      METHODS: The medical records and MR images of 402 adult patients with chronic
      headache were retrospectively reviewed. All patients had been evaluated and
      referred by the neurology service. The findings were categorized as either
      negative or positive for major abnormality. Multivariate analysis with a linear
      logistic regression technique was performed on the clinical data, which included
      patient age, patient sex, and headache type. RESULTS: Major abnormalities were
      found in 15 patients (3.7%), consisting of seven women (2.4%) and eight men
      (6.9%). Major abnormalities were found in 0.6% of those with migraine headaches,
      1.4% with tension headaches, none with mixed migraine and tension headaches,
      14.1% with atypical headaches, and 3.8% with other types of headaches.
      Multivariate analysis showed that the atypical headache type was the most
      significant predictor of major abnormality. CONCLUSION: The yield of major
      abnormalities found with brain MR imaging in patients with isolated chronic
      headache is low. However, those patients with atypical headaches have a higher
      yield of major abnormalities and may benefit from imaging.

PMID- 11345272
TI  - Glossary of molecular imaging terminology.

PMID- 11345273
TI  - Sex ratio in the offspring of male radiologists.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study was to determine if male
      radiologists predominantly father daughters and, if so, to investigate the
      association between this skewed sex ratio of offspring and radiation exposure.
      MATERIALS AND METHODS: Questionnaires completed by 586 male radiologists in Japan
      provided data regarding the radiologist's age, length of employment in radiology,
      if he had ever received radiation doses higher than that recommended by the
      International Commission on Radiological Protection, the sex of each child
      fathered, and the birth date of each child. RESULTS: As a group, male
      radiologists tended to father a lower proportion of boys (48.47%) compared with
      the control group (51.46%), and the relative risk was 1.13 (95% confidence
      interval [CI]: 1.00, 1.27). Offspring of highly irradiated radiologists, however,
      had a reduced proportion of males (34.48%), with a significantly (P = .002)
      increased relative risk of 2.01 (95% CI: 1.29, 3.13). CONCLUSION: X-ray exposure
      may explain the reduced percentage of sons in the offspring of male radiologists.

PMID- 11345274
TI  - Speech recognition and transciption.

PMID- 11345275
TI  - National Cancer Institute initiative: Lung image database resource for imaging
      research.
AB  - Preliminary clinical studies suggest that spiral computed tomography (CT) of the
      lungs can improve early detection of lung cancer in high-risk individuals. More
      clinical studies are needed, however, before public health recommendations can be
      proposed for population-based screening. Spiral CT generates large-volume data
      sets and thus poses problems in terms of implementation of efficient and cost
      effective screening methods. Image processing algorithms such as computer
      assisted diagnostic (CAD) methods have the potential to assist in lesion (eg,
      nodule) detection on spiral CT studies. CAD methods may also be used to
      characterize nodules by either assessing the stability or change in size of
      lesions based on evaluation of serial CT studies, or quantitatively measuring the
      temporal parameters related to contrast dynamics when using contrast material
      enhanced CT studies. CAD methods therefore have the potential to enhance the
      sensitivity and specificity of spiral CT lung screening studies. Lung cancer
      screening studies now under investigation create an opportunity to develop an
      image database that will allow comparison and optimization of CAD algorithms.
      This database could serve as an important national resource for the academic and
      industrial research community that is currently involved in the development of
      CAD methods. The National Cancer Institute request for applications (RFA) (CA-01
      001) has already been announced (April 2000) to establish and support a
      consortium of academic centers to develop this database, the consortium to be
      referred to as the Lung Image Database Consortium (LIDC). This RFA is now closed.
      Five academic sites have been selected to be members of the LIDC, the first
      meeting of this consortium is planned for spring of 2001, and a public meeting is
      to be held in 2002. This report is abstracted from the previously published RFA
      to serve as an example of how an initiative is developed by the National Cancer
      Institute to support a research resource. For specific details of the RFA, please
      access the following Internet site: http://www. nci.nih.gov/bip/NCI
      DIPinisumm.htm#a11.

PMID- 11345276
TI  - Responsibility for quality IgE antibody results rests ultimately with the
      referring physician.

PMID- 11345277
TI  - Nasal provocation testing: a review.
AB  - OBJECTIVE: This review focuses on the uses of nasal provocation testing (NPT) for
      scientific investigations of the mechanisms of allergic and nonallergic rhinitis.
      It also describes the use of NPT as a diagnostic tool in clinical practice. The
      indications, contraindications, advantages, and limitations of different
      techniques for evaluation of nasal responses are reviewed. The paper familiarizes
      investigators with particulars of different nasal delivery systems, provocation
      agents, nasal patency measurements, secretion collection, and nasal lavage
      techniques. DATA SOURCES: Relevant publications obtained from a literature
      review. STUDY SELECTION: Relevant publications on the topics of NPT, allergic,
      and nonallergic rhinitis were critically evaluated. RESULTS AND CONCLUSIONS: To
      date, NPT has been used primarily as a research tool for the investigation of
      allergic and nonallergic rhinitis with a wide variety of techniques depending on
      the specific scientific purposes. NPT will continue to provide useful information
      about the pathogenesis of airway diseases. Standardized nasal provocation testing
      has the potential to become a more frequently used clinical test in the diagnosis
      of allergic and occupational rhinitis and for determination of the appropriate
      and focused therapy.

PMID- 11345278
TI  - Precision and accuracy of commercial laboratories' ability to classify positive
      and/or negative allergen-specific IgE results.
AB  - BACKGROUND: Accurate and reliable evaluation of the presence or absence of
      allergen-specific IgE is important in the differential diagnosis of allergic
      disease. A variety of different commercial tests are available for this purpose.
      There are few data available to judge how the results of these different tests
      compare with one another in everyday use. OBJECTIVE: To examine prospectively the
      extent of comparability among specific IgE results from different laboratories.
      METHODS: Six diagnostic laboratories employing five different methods to assay
      specific IgE were selected. Aliquots from 26 serum samples that contained
      variable levels of IgE specific to 17 common aeroallergens were sent in
      triplicate to each study laboratory during a 6-week time period. Results were
      reported numerically and by class scores and then compared by examining their
      concordance using Kendall's W nonparametric statistical test. In addition, cut
      off values were compared by a best agreement analysis using reported results.
      Reproducibility was determined using precision profiles based upon the
      coefficient of variation among triplicates for each allergen across the range of
      reported results. RESULTS: In all, 7,813 tests were analyzed. Concordance among
      different assays in commercial use with one exception was not good. This was
      particularly true around the cut-off region where most assays demonstrated high
      imprecision. The Pharmacia CAP System used by two different laboratories
      demonstrated highly comparable results with good precision. Some assays were
      reproducible but not accurate. Others were neither reproducible nor accurate.
      CONCLUSIONS: The results of this study indicate that not all commercial
      laboratories/assays for specific IgE provide reproducible and accurate data.
      Significant potential for misdiagnosis was detected for some reported results.
      Methods were identified that do give sensitive, accurate, and reproducible
      results.

PMID- 11345279
TI  - Is it important to perform pollen skin prick tests in the season?
AB  - BACKGROUND: Seasonal exposure to pollens causes the characteristic symptoms of
      respiratory allergy as well as an increase in specific IgE levels and
      inflammatory mediator release. However, little is known about the effect of
      natural allergen exposure on the skin test reactivity of patients with seasonal
      allergy. OBJECTIVE: The aim of this study was to investigate the monthly
      variation in skin test reactions with pollen allergens during pollen season and
      its relation to pollen counts. METHODS: Fifteen subjects with seasonal allergic
      rhinitis and/or asthma (4 male, 11 female) between the ages of 13 and 52 (mean
      33.9 +/- 2.9) who lived in Ankara, Turkey were selected for this study. Patients
      were monitored from the beginning of March to the end of September 1997, and skin
      prick tests were performed using 5 grass, 12 tree, and 5 weed pollen allergen
      extracts every month. Atmospheric pollen grains were counted in the Ankara area
      between January and December, 1997. RESULTS: There were small but statistically
      significant increases in tree pollen-induced wheal sizes in May when compared
      with other months (P < 0.05). Skin test reactivity was correlated with tree
      pollen counts (r = 0.978, P < 0.05). There was not a significant difference in
      skin test reactivity to grass and weed pollens between months. CONCLUSIONS:
      Although skin test reactivity may be slightly greater to tree pollen during the
      tree pollen season, the timing of skin testing is not a critical determinant in
      patients with pollen allergy.

PMID- 11345280
TI  - Twenty-four hours of activity of cetirizine and fexofenadine in the skin.
AB  - BACKGROUND: Cetirizine and fexofenadine, the active metabolite of terfenadine,
      are powerful and well-tolerated H1 receptor antagonists effective in the
      treatment of skin and nose atopic diseases. OBJECTIVE: We have compared the
      pharmacodynamic activity of the two antihistamines at therapeutic dosages,
      cetirizine at 10 mg and fexofenadine at 120 mg and 180 mg, on histamine-induced
      skin reactivity during a 24-hour period after single intake. METHODS: Twenty-six
      healthy volunteers participated in a randomized, double-blind, crossover, placebo
      controlled study. The areas of wheal and flare induced by histamine (100 mg/mL)
      administered by prick test were measured at 0, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24
      hours postdose. Statistical analysis of the areas under the time-response curves
      was performed by a Friedman's ANOVA followed by a Wilcoxon test and Bonferroni's
      correction. RESULTS: The three active treatments clearly inhibited the wheal and
      flare areas throughout the 24-hour period compared with placebo. Maximal
      inhibition occurred at 4 hours postdose. Between 4 and 24 hours postdose, the
      time course of inhibition by cetirizine differed significantly (P < 0.001) from
      that by fexofenadine at either dose, which did not differ from each other. At 24
      hours, fexofenadine inhibited <40% of the skin reaction, whereas cetirizine
      reduced 60% of the wheal. The duration of effect, considered as the time for
      wheal to be inhibited by at least 70%, also significantly favored cetirizine (19
      hours) compared with fexofenadine (9.3 and 8.5 hours for 180 and 120 mg,
      respectively; P < 0.001). Consistency of activity was evaluated by the frequency
      of total inhibition of the wheal (> or =95%). Consistency was observed in 26 of
      26 participants for cetirizine, 21 of 26 for fexofenadine, 180 mg, and 10 of 26
      for fexofenadine, 120 mg (P < 0.001), suggesting better consistency for
      cetirizine. There was no serious adverse event. CONCLUSIONS: Our study clearly
      shows better duration of action and consistency of the antihistaminic activity of
      cetirizine compared with fexofenadine (120 and 180 mg) in the histamine-induced
      skin reaction during a 24-hour period.

PMID- 11345281
TI  - Quality of life indices may be predictive of placebo and medication response to
      treatment for allergic rhinitis.
AB  - BACKGROUND: Quality of life (QOL) is known to be an important clinical endpoint
      in determining medication efficacy; however, the predictive value of QOL indices
      for response to medication or placebo has not been tested. OBJECTIVE: To
      determine whether a correlation between measures of QOL and response to
      medication/placebo exists in an evaluation of budesonide for allergic rhinitis.
      METHODS: Two hundred nine participants completed the 36-item short-form health
      QOL survey at screening for entry into a study examining the onset of action of
      budesonide in an allergen challenge system. During the treatment phase, symptom
      assessments were recorded hourly after dosing of double-blind medication.
      Participants were determined to be responders or nonresponders to study
      medication. A responder was defined as a participant who rated medication
      effectiveness as fair to excellent with regard to symptom relief, for three
      consecutive hourly assessments during the study day or one whose total symptom
      score decreased by > or =25% for three consecutive hourly assessments. Baseline
      QOL scores were compared between responders and nonresponders. RESULTS:
      Differences were noted among responders and nonresponders on the basis of whether
      budesonide or placebo was received. Ratings of general health perception, pain,
      physical function, and role limitation due to physical health were significantly
      lower among participants who responded to placebo, compared with placebo
      nonresponders. In addition, the overall physical health and 36-item short-form
      health survey averages were significantly lower. Differences between responders
      and nonresponders to budesonide did not reach statistical significance.
      CONCLUSIONS: Lower baseline QOL scores were associated with a clinically
      significant response to placebo in a trial of treatment for allergic rhinitis.
      QOL may be a factor in participant response to medication in clinical studies
      and, hence, a predictor of outcome.

PMID- 11345282
TI  - Dose-ranging study of mometasone furoate dry powder inhaler in the treatment of
      moderate persistent asthma using fluticasone propionate as an active comparator.
AB  - BACKGROUND: Mometasone furoate (MF; Schering-Plough, Madison, NJ), is a
      glucocorticoid with high local potency and low potential systemic availability.
      OBJECTIVES: To compare the relative efficacy and safety of a new formulation of
      MF, coupled with a recently designed dry powder inhaler (DPI), in the treatment
      of patients with moderate persistent asthma. Fluticasone propionate administered
      by Diskhaler (FP Diskhaler, 250 microg twice a day; Glaxo Wellcome, Research
      Triangle Park, NC) was used as an active control. DESIGN: A randomized, parallel
      group, double-blind (for MF-DPI dosage), evaluator-blind (for MF-DPI vs FP)
      trial. SETTING: Sixty centers in 20 countries. PATIENTS: Seven hundred thirty
      three patients with moderate persistent asthma on inhaled corticosteroid
      treatment. INTERVENTIONS: Discontinuation of previous inhaled corticosteroid and
      initiation of one of four study treatments: three doses of MF-DPI (100, 200, and
      400 microg twice daily) and one of FP (250 microg twice daily >12 weeks).
      RESULTS: FEV1 (primary efficacy variable) was evaluated as the mean change from
      baseline to endpoint (last evaluable visit). All dosage groups showed improvement
      at endpoint. Only 400 microg twice daily of MF-DPI (+0.19 L) was statistically
      different from 100 microg twice daily of MF-DPI (+0.07 L; P = 0.02). MF-DPI (200
      microg twice daily) and FP Diskhaler groups showed similar improvement (+0.16 L).
      Greater improvement in most secondary variables (forced expiratory flow between
      25% and 75% of vital capacity, and morning and evening peak expiratory flows)
      also resulted from treatment with 200 or 400 microg twice daily of MF-DPI or with
      FP Diskhaler, compared with 100 microg twice daily of MF-DPI. Overall, a total
      daily 800-microg dose of MF-DPI conferred no significant additional benefit >400
      microg of MF-DPI. The incidence of oral candidiasis was 1%, 7%, 10%, and 10% in
      the 100, 200, and 400 microg twice daily of MF-DPI and FP groups, respectively.
      CONCLUSIONS: A total daily dose of 400 microg of MF-DPI provides clinical benefit
      comparable to that observed with a total daily dose of 500 microg of FP
      Diskhaler.

PMID- 11345283
TI  - A childhood asthma severity scale: symptoms, medications, and health care visits.
AB  - BACKGROUND: Although there are current measures to evaluate childhood asthma
      severity for clinical diagnosis and treatment, there is no standard valid measure
      to evaluate childhood asthma severity for large-scale epidemiologic studies.
      OBJECTIVES: To develop and test a childhood asthma severity scale (CHAS) for
      clinimetric validity and to determine differences in symptoms, medication use,
      and health care visits by participant characteristics. METHODS: Eight hundred
      ninety-seven actively asthmatic children under the age of 12 years were selected
      from a general population of children. Children were selected from a screening
      questionnaire administered at six Connecticut hospitals that serve large minority
      populations in Bridgeport, New Haven, Hartford, and Danbury and one hospital
      serving south central Massachusetts. Twelve-month baseline data for a prospective
      cohort study of childhood asthma severity were collected on a monthly basis
      through home interviews. Home interviews addressed questions on daily symptoms,
      medication use, and health care visits. A severity scale was constructed using
      three dimensions: symptoms, medication use, and health care visits. RESULTS: CHAS
      has sufficient preliminary content, construct, and predictive validity. Despite
      similarities in symptoms, there were health care utilization and medication
      differentials according to race and ethnicity, insurance status, family income,
      and maternal education. CONCLUSIONS: CHAS is a potentially useful measure of
      asthma severity for large-scale epidemiologic studies. It seems that CHAS has
      sufficient clinimetric properties.

PMID- 11345284
TI  - Unusual presentations of food allergy.
AB  - OBJECTIVE: This presentation is designed to critically review information on
      presentations of food hypersensitivity reactions that may be considered unusual
      regarding the source or nature of allergen, route of exposure, or clinical
      manifestation. DATA SOURCES: Information has been gathered primarily through a
      thorough search of the English literature relevant to human subjects. Some
      clinical cases were also included from the author's own clinical experience.
      STUDY SELECTION: Information summarized here was critically selected on the basis
      of proven or acceptable scientific validity. RESULTS: The findings indicate that
      food allergy presentation can be unusual in three main aspects. First, the
      offending allergen may not be the obvious food that was ingested or be a food
      protein incorporated in a nonfood product. Second, systemic reactions can be
      provoked by very minute quantities of food allergens that may even get access
      through noningestant routes, eg, inhalation, odor, skin contact, or mucous
      membrane contact. Third, the clinical manifestations are not limited to the few
      gastrointestinal, cutaneous, and respiratory symptoms with which we are generally
      familiar. CONCLUSIONS: The extent of food allergy presentation is more than has
      been generally realized. Our awareness of such unusual presentations adds new
      knowledge and should prompt our interest in carefully evaluating patients with
      obscure allergic reactions for possible food allergy.

PMID- 11345285
TI  - Testing the reliability of old and new features of a new electronic monitor for
      metered dose inhalers.
AB  - BACKGROUND: Poor adherence to treatment regimens is hypothesized to be, in part,
      responsible for the extensive morbidity and mortality associated with asthma.
      Electronic monitors are the most accurate means available for measuring
      adherence, but their use has been limited by reports questioning the reliability
      and validity of their data. OBJECTIVE: To test the reliability and accuracy of
      the MDILog (Medtrac Technologies, Lakewood, CO), a new electronic monitor of
      metered dose inhalers (MDIs), and to test its unique features. METHODS: Brief
      experiments were performed comparing a written diary to the electronic record
      using three MDILogs. The following features were studied: reporting of time and
      date of an actuation, recording of the occurrence of an actuation of the MDI,
      sensing and timing of inhalations, sensing of shaking of the MDI canister, and
      recording of multiple actuations. RESULTS: Clocking was accurate 100% of the
      time. Actuation agreed with the paper record 97% to 100%, inhalation 82% to 100%,
      shaking 86% to 95%. Agreement of late inhalations and multiple actuations with
      paper records was at least 98%. CONCLUSIONS: The MDILog yields accurate
      information and is more reliable than previously described monitors. Its new
      features allow more detailed study of how patients use inhalers by allowing
      evaluation of how patients inhale and whether they shake the inhaler canister
      before use.

PMID- 11345286
TI  - Extrinsic allergic alveolitis from a proteolytic enzyme.
AB  - BACKGROUND: Subtilisins are proteolytic enzymes of bacterial origin found in
      detergents. They are high-molecular-weight antigens and have been implicated in
      allergic rhinitis and asthma. OBJECTIVE: This report describes a case of
      extrinsic allergic alveolitis due to subtilisins in a liquid cleaner. METHODS:
      Clinical, radiologic, and serologic information were used to make the diagnosis.
      CASE REPORT: A 53-year-old woman developed respiratory symptoms while working
      with a cleaner containing subtilisins. Her symptoms intensified in the work
      environment and improved away from work. A computed tomography scan demonstrated
      alveolar and interstitial infiltrates with subsequent scarring. A pulmonary
      function study revealed a restrictive pattern with diminished diffusion capacity.
      Bronchoalveolar lavage showed lymphocytosis and all cultures were negative.
      Precipitating antibodies to the enzyme were found in the patient's serum. Her
      symptoms improved once she changed her occupation. CONCLUSIONS: The combination
      of the patient's clinical history, physical, laboratory, and radiologic findings
      support the diagnosis of extrinsic allergic alveolitis from the enzyme contained
      in the cleaner.

PMID- 11345287
TI  - Prevalence and severity of asthma, rhinitis, and atopic eczema in 13- to 14-year
      old schoolchildren from the northeast of England.
AB  - OBJECTIVE: To investigate the prevalence and severity of asthma, rhinitis, and
      atopic eczema in schoolchildren from the northeast of England. METHODS: We
      randomly selected 3,000 children from 80 schools. We used the ISAAC
      (International Study of Asthma and Allergies in Childhood) written questionnaire.
      RESULTS: The lifetime prevalence rates of symptoms were: rhinitis, 32.8%;
      wheezing, 31.3%; hay fever, 23.7%; and self-reported asthma, 22.3%. Rhinitis was
      reported by 53% and 61% of boys and girls with asthma, respectively. Girls 13 to
      14 years of age had higher prevalence rates of asthma, rhinitis, and eczema
      symptoms than boys; a reverse sex ratio has been shown in this age group. Atopic
      eczema was reported by 32% of boys with asthma and 37% of girls with asthma.
      CONCLUSIONS: The prevalence rates of reported asthma, and symptoms suggestive of
      asthma, were higher than those previously reported in UK children. The present
      study would be a suitable baseline for monitoring future trends in the prevalence
      and severity of asthma and allergic disorders among these children, and provides
      a framework for further etiologic research into the genetics, lifestyle,
      environmental, and medical care factors affecting these conditions.

PMID- 11345288
TI  - Intranasal mometasone furoate reduces late-phase inflammation after allergen
      challenge.
AB  - BACKGROUND: Allergen specific nasal challenge (ASNC) is an optimal model to study
      the pathophysiologic mechanisms sustaining allergic inflammation, particularly
      the adhesion molecules promoting cellular infiltration of nasal mucosa. Topical
      corticosteroids have been accepted as a highly effective anti-inflammatory
      therapy for allergic rhinitis. OBJECTIVE: The aim of this double-blind,
      randomized, placebo-controlled study was the evaluation of inflammatory events,
      during the late-phase, after a 2-week treatment with nasal mometasone furoate
      (MF), 200 microg daily, or placebo, using the model of ASNC. METHODS: A total of
      42 patients with allergic rhinitis underwent nasal challenge before and after
      treatment. The following parameters were evaluated at baseline, and 6 hours (late
      phase) after ASNC: 1) nasal symptoms (rhinorrhea, itching, sneezing,
      obstruction); 2) inflammatory cells (eosinophils and neutrophils); 3) eosinophil
      cationic protein (ECP) and tumor necrosis factor-alpha (TNF-alpha) in nasal
      lavage; and 4) intercellular adhesion molecule-1 expression on nasal epithelial
      cells. RESULTS: MF nasal spray was associated with late-phase reductions of: 1)
      clinical symptoms (P < 0.03); 2) eosinophil (P < 0.004) and neutrophil (P <
      0.003) infiltration; 3) ECP (P < 0.001) and TNF-alpha (P < 0.05); and 4)
      intercellular adhesion molecule-1 expression on nasal epithelial cells (P <
      0.001). CONCLUSIONS: The present results demonstrate that MF has a significant
      effect on late-phase events, reducing the cellular influx and activation.

PMID- 11345289
TI  - Atypical expiratory flow volume curve in an asthmatic patient with vocal cord
      dysfunction.
AB  - BACKGROUND: Vocal cord dysfunction can coexist with or masquerade as asthma.
      Vocal cord dysfunction, when coexistent with asthma, contributes substantially to
      the refractory nature of the respiratory problem. OBJECTIVE: To report a case of
      an asthmatic patient with vocal cord dysfunction and a previously unreported
      unique expiratory flow volume curve. RESULTS: A 16-year-old female, known to have
      asthma, developed increased frequency of her asthma exacerbations. Spirometry,
      during symptoms, showed an extrathoracic airway obstruction with a reproducible
      unique abrupt drop and rise in the expiratory flow volume loop. Laryngoscopy
      showed adduction of the vocal cords during inspiration and expiration.
      CONCLUSIONS: We report a unique expiratory flow volume curve in an asthmatic with
      vocal cord dysfunction that resolved with panting maneuvers. Speech and
      psychological counseling helped prevent future attacks.

PMID- 11345290
TI  - Clinical and immunologic changes after allergen immunotherapy with Hop Japanese
      pollen.
AB  - BACKGROUND AND OBJECTIVE: Hop Japanese (Hop J) pollen has been reported as one of
      the major causative pollen allergens in the autumn season. There have been no
      published data regarding the clinical and immunologic effects of Hop J pollen
      immunotherapy in sensitized patients. In this study, we evaluated clinical and
      immunologic effects of Hop J immunotherapy. PATIENTS AND METHODS: Pollens were
      collected in our area, and "Depo-Hop J" was prepared in the laboratory of
      Allergopharma (Reinbek, Germany). Fifteen asthmatic patients who had Hop J
      immunotherapy for > 1 year were enrolled. Their clinical parameters, such as
      asthma symptom scores, were monitored. Skin reactivity to Hop J and degree of
      airway hyperresponsiveness to methacholine were measured before and 1 year after
      the immunotherapy. Sera were collected before the immunotherapy, at the end of
      initial therapy, and 1 year after the therapy. Serum total IgE levels were
      compared by radioimmunoassay. Serum-specific IgE, IgG1, and IgG4 levels to Hop J
      were compared by ELISA. To evaluate the changes of cellular mechanisms, soluble
      CD30 (sCD30), soluble interleukin (IL)-2 receptor (sIL-2R), soluble CD23 (sCD23),
      and IL-10 levels were measured by ELISA. RESULTS: Specific IgG1 and IgG4 levels
      began to increase at the end of the initial therapy (P < 0.05) with significant
      decreases in symptom scores (P < 0.05), whereas total and specific IgE levels
      showed variable responses during the immunotherapy with no statistical
      significance (P > 0.05). Serum sIL-2R and sCD30 levels decreased significantly (P
      < 0.05) 1 year after immunotherapy. No significant changes were noted in sCD23,
      IL-10, skin reactivity to Hop J, or airway responsiveness to methacholine (P >
      0.05). CONCLUSIONS: We are certain that Hop J allergen immunotherapy, if carried
      out properly according to suitable indications, can favorably influence asthma.
      Thus, an increase in specific IgG4 and IgG1 antibodies and reduction of a
      possible Th2 lymphocyte marker (sCD30) may be associated with symptomatic
      improvements.

PMID- 11345291
TI  - Risk factors for the persistence of respiratory symptoms in childhood asthma.
AB  - OBJECTIVE: To evaluate the parameters which could predict the persistence of
      respiratory symptoms in asthmatic children who have been treated with a
      considerably uniform therapy. METHODS: A retrospective review was performed on
      the records of 279 children with asthma. An end of study visit, results of
      spirometry and prick tests completed the data. The mean age at referral and at
      final visit was 6.2 +/- 3.7 years and 8.9 +/- 4.1 years, respectively; and the
      children were followed up for a mean of 3 +/- 1.2 years. RESULTS: Eighty-five of
      the 279 patients (30%) experienced no respiratory symptoms in the previous 12
      months. There was no significant difference between those with and without
      current respiratory symptoms with respect to age, sex, age at onset of symptoms,
      duration of followup, age at referral, therapeutic choice, severity of asthma and
      duration of symptoms at referral. For subjects with current respiratory symptoms
      the initial serum total IgE level, and the percentage of RAST/prick test
      positivity was significantly higher than those without current respiratory
      symptoms (P = 0.0027, P = 0.011, respectively). Although the initial FEF 25%-75%,
      FEV1, and FEV1/FVC was significantly lower in those with current respiratory
      symptoms (P = 0.003; P = 0.005; and P = 0.04, respectively), there was no
      statistically significant difference between lung functions of the two groups at
      the end of followup. The persistence of respiratory symptoms was significantly
      predicted by initial FEF25%-75% and sensitivity to allergens (P = 0.03 and P =
      0.04, respectively). CONCLUSIONS: We concluded that the risk factors for the
      persistence of respiratory symptoms in our patient population have been low
      FEF25%-75% value and sensitivity to allergens at referral.

PMID- 11345292
TI  - Outdoor air pollutants derived from industrial processes may be causally related
      to the development of asthma in children.
AB  - BACKGROUND: There is no consistent evidence that outdoor air pollutants are
      involved in the development of asthma. OBJECTIVE: The aim of this study was to
      determine whether outdoor air pollutants derived from industrial processes were
      related to the prevalence of asthma, bronchial hyperresponsiveness, and atopy in
      exposed children. METHODS: A total of 7,511 children from 7 to 12 years of age
      were recruited in the study. Eight hundred eighty-eight of 1,009 (88%) of the
      subjects living around industrial factories and 5,998 of 6,502 (92%) living in a
      less polluted neighboring area responded to the ISAAC questionnaire. A total of
      1,492 subjects 8 to 9 years old underwent skin prick tests for 11 common
      aeroallergens. A total of 732 of the subjects from 8 to 9 years of age underwent
      bronchial provocation tests with hypertonic saline (BPT-HS). RESULTS: The
      prevalence of ever experiencing wheezing and wheeze during the last 12 months was
      25.6%, and 18.8% among the children living in the more polluted area. This was
      significantly higher than for those living in the less polluted area (14.2% and
      9.0%, respectively). The positive rate of BPT-HS (the provocative dose of
      hypertonic saline causing 20% fall of FEV, < or = 23 mL) was higher among those
      in the more polluted area than in children living in the less polluted area
      (12.2% vs 7.5%). However, the rate of atopy based on the skin tests was the same
      in the two groups (28.3% vs 30.6%). CONCLUSIONS: The prevalence of asthma and
      bronchial hyperresponsiveness was higher among children living around the heavily
      industrial area compared with those living in the less polluted area, despite
      similar atopic sensitization.

PMID- 11345293
TI  - Unmasking of acquired autoimmune C1-inhibitor deficiency by an angiotensin
      converting enzyme inhibitor.
AB  - BACKGROUND: A majority of angioedema arise from unknown etiologies. Angioedema
      may also arise from medications or deficiency of C1-esterase inhibitor (C1-INH);
      either of these may lead to recurrent, sometimes life-threatening attacks of
      subcutaneous or submucosal edema if the angioedema involves the tongue, throat,
      or larynx. We describe a patient with unknown acquired C1-INH deficiency, who
      experienced only mild attacks of angioedema before treatment with an angiotensin
      converting enzyme (ACE) inhibitor. This therapy led to life-threatening
      respiratory distress. OBJECTIVE: To investigate this patient's life-threatening
      angioedema. METHODS: Serum protein electrophoresis and immunofixation were
      performed. The titer of anti-C1-inhibitor autoantibody was determined by ELISA,
      and the specificity of the autoantibody demonstrated by using purified C1-INH to
      block binding in the ELISA. Finally, fractions from the immunoelectrophoresis gel
      were tested for C1-INH autoantibody by ELISA. RESULTS: Complement activation was
      documented by reduced C1-INH, C1q, and C4, and the patient was found to have an
      autoantibody of IgG2 isotype specific for C1-INH. After discontinuation of the
      ACE inhibitor, he continued to have decreased C1-INH and positive C1-INH
      autoantibodies. CONCLUSIONS: This case describes a patient who had a history of
      mild facial and extremity swelling with abdominal symptoms before ACE inhibitor
      treatment; this medication resulted in life-threatening respiratory distress. The
      use of the ACE inhibitor may have unmasked this patient's acquired autoimmune C1
      INH deficiency.

PMID- 11345295
TI  - Occupational asthma and rhinitis caused by multiple herbal agents in a
      pharmacist.
AB  - BACKGROUND: Herb agents have been widely used for centuries in the Orient and
      they have been cultivated throughout Asia. There have been a few cases of
      occupational allergy caused by herb materials. We report a case of occupational
      asthma and rhinitis caused by six herb materials in a pharmacist working at a
      pharmacy. OBJECTIVE: We sought the role of immediate hypersensitivity in herbal
      agent-induced asthma in a pharmacist. METHODS AND RESULTS: The patient had strong
      positive responses on skin prick test to extracts of six herb materials: Chunkung
      (Cnidii rhizoma), Banha (Pinellia ternata), Sanyak (Dioscorea radix), Kangwhal
      (Ostericum koreanum), Danggui (Angelica radix), and Kunkang (Zingiberis rhizoma).
      Bronchoprovocation tests showed an early asthmatic response to Danggui extract.
      Serum specific IgE antibodies to Chunkung, Banha, and Sanyak were detected by
      ELISA with no specific IgE bindings to Kangwhal, Danggui, and Kunkang extracts.
      Twelve percent sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS
      PAGE) and IgE immunoblotting revealed one IgE binding component (60 kD) within
      Chunkung extract, two (10, 25 kD) in Banha, and four (33, 34, 65, 98 kD) in
      Sanyak. Basophil histamine release test revealed that Danggui extract could
      release a greater amount of histamine from basophils in the patient than in a
      healthy control. CONCLUSIONS: Chunkung, Banha, and Sanyak may induce IgE-mediated
      bronchoconstriction in an exposed worker, and Danggui can cause
      bronchoconstriction by direct histamine-releasing effect from mast cells in a
      sensitized patient.

PMID- 11345294
TI  - Hospital admissions and death rates from asthma in Kuwait during pre- and post
      Gulf War periods.
AB  - BACKGROUND: The aim of the present study is to compare hospital admissions and
      death rates from asthma between pre (1987 to 1989)- and post (1992 to 1994)-Gulf
      War periods. METHODS: Data on annual hospital admissions by nationality and age,
      per International Statistical Classification of Diseases 493, were collected from
      the Health Statistics Department, Ministry of Health, Kuwait, and were analyzed
      with population data from the Annual Statistical Reports, Ministry of Planning,
      Kuwait. RESULTS: A total of 12,113 patients with asthma were admitted to various
      hospitals in Kuwait during the pre-Gulf War period compared with 9,771 patients
      during the post-Gulf War period. The average annual admissions rates per 100,000,
      people were 205 and 217, respectively, for the pre- and postwar periods. Total
      number of admissions showed an increase among Kuwaiti nationals during the study
      period. There were 95 deaths during the prewar period compared with 72 deaths
      during the postwar period. The mean annual death rates per 100,000 people were
      1.60 and 1.59 respectively, for the pre- and post-Gulf War periods. CONCLUSIONS:
      This study did not show any statistically significant differences in either
      hospital admissions for or death rates attributable to asthma in the pre- and
      post-Gulf War periods in Kuwait. However, the number of hospital admissions in
      young adult Kuwaiti nationals increased. This study suggests hospital admissions
      and deaths from asthma did not increase after the invasion of Kuwait.

PMID- 11345296
TI  - Western aspen.

PMID- 11345297
TI  - Committee thinks rabies postexposure protocol raises public health concerns.

PMID- 11345298
TI  - Differing opinions on treatment of immune-mediated hemolytic anemia.

PMID- 11345299
TI  - Thinks rising costs reflect increased quality of medicine.

PMID- 11345300
TI  - Believes raw food diet study was incomplete.

PMID- 11345301
TI  - In praise of canine flatulence research.

PMID- 11345302
TI  - What is your diagnosis? Attenuation of the dorsal and lateral columns of contrast
      material and slight ventral deviation of the dorsal column at T12-T13 and T13-L1.

PMID- 11345303
TI  - When can failure to inform support a malpractice claim?

PMID- 11345305
TI  - Epidemiologic study of risk factors for lower urinary tract diseases in cats.
AB  - OBJECTIVE: To determine proportional morbidity rates (PMR) and risk factors for
      lower urinary tract diseases (LUTD) in cats. DESIGN: Case-control study. SAMPLE
      POPULATION: Records of 22,908 cats with LUTD and 263,168 cats without LUTD.
      PROCEDURE: Data were retrieved from the Purdue Veterinary Medical Data Base.
      Descriptive statistics and univariate logistic regression analyses were performed
      to assess whether breed, age, sex, and neutering status were associated with
      different causes of LUTD. RESULTS: Mean PMR for LUTD irrespective of cause was
      8/100 cats (range, 2 to 13/100 cats). Increased risk for urocystolithiasis
      (Russian Blue, Himalayan, and Persian cats), bacterial urinary tract infections
      (UTI; Abyssinian cats), congenital urinary tract defects (Manx and Persian cats),
      and urinary incontinence (Manx cats) was detected. Cats between 2 and < 7 years
      of age had increased risk for urethral plugs, neurogenic disorders, congenital
      defects, and iatrogenic injuries. Cats between 4 and < 10 years of age had
      increased risk for urocystolithiasis, urethral obstructions, and idiopathic LUTD.
      Cats > or = 10 years of age had increased risk for UTI and neoplasia. Castrated
      males had increased risk for each cause of LUTD except UTI and incontinence.
      Spayed females had increased risk for urocystolithiasis, UTI, and neoplasia.
      Sexually intact females had decreased risk for each cause of LUTD except
      neurogenic disorders and iatrogenic injuries. CONCLUSION AND CLINICAL RELEVANCE:
      Specific breed, age, sex, and neutering status may be associated with specific
      types of feline LUTD. Knowledge of patient risk factors for LUTD may facilitate
      development of surveillance strategies that enhance earlier detection.

PMID- 11345304
TI  - Sensitivity and specificity of methods of assessing the regional lymph nodes for
      evidence of metastasis in dogs and cats with solid tumors.
AB  - OBJECTIVE: To determine sensitivity and specificity of physical examination, fine
      needle aspiration, and needle core biopsy of the regional lymph nodes for
      evidence of metastasis in dogs and cats with solid tumors. DESIGN: Case series.
      ANIMALS: 37 dogs and 7 cats. PROCEDURE: Regional lymph nodes were evaluated by
      means of physical examination (palpation), fine-needle aspiration, and needle
      core biopsy. Results were compared with results of histologic examination of the
      entire lymph node, the current standard. RESULTS: Tumors included 18 sarcomas, 16
      carcinomas, 7 mast cell tumors, and 3 other tumors. Carcinomas were more likely
      to have metastasized to the regional lymph node (7/16 animals) than were sarcomas
      (2/18). Sensitivity and specificity of physical examination were 60 and 72%,
      respectively. Sensitivity and specificity of cytologic examination of fine-needle
      aspirates were 100 and 96%, respectively. Sensitivity and specificity of
      histologic examination of needle core biopsy specimens were 64 and 96%,
      respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that fine
      needle aspiration may be a sensitive and specific method of evaluating the
      regional lymph nodes in dogs and cats with solid tumors, because results
      correlated well with results of histologic examination of the entire lymph node.
      Physical examination alone was not a reliable method and should not be used to
      decide whether to aspirate or biopsy the regional lymph nodes.

PMID- 11345306
TI  - Suspected Clostridium difficile-associated diarrhea in two cats.
AB  - Two adult cats from the same household developed acute diarrhea. Clostridium
      difficile toxins were detected in the feces of both cats, whereas other
      recognized causes of diarrhea were not identified. Supportive medical treatment
      and metronidazole were administered and both cats responded well. A fecal sample
      obtained from 1 of the affected cats after treatment and a fecal sample obtained
      from a clinically normal cat in the household did not contain C difficile toxins.
      The role of C difficile in enteric disease in cats has not been extensively
      studied and is unclear; however, our findings suggest that toxigenic strains of C
      difficile may cause diarrhea in cats.

PMID- 11345307
TI  - Itraconazole for treatment of sporotrichosis in a dog residing on a Christmas
      tree farm.
AB  - Sporotrichosis was diagnosed in a 2-year-old male Golden Retriever that was
      allowed to roam free on the owner's Christmas tree farm in Minnesota. Clinical
      signs had been evident for 1 month and included swelling of the claw bed of the
      third digit on the left forelimb and a fluctuant nodular lesion in the area of
      the left carpus. Few organisms were seen in affected tissues, and diagnosis was
      confirmed on the basis of results of fungal culture. The condition responded to
      treatment with itraconazole. Previous reports of sporotrichosis in dogs have
      described lesions that were distributed predominantly on the head, ears, and
      trunk. A history of exposure to environments that favor survival of the organism
      may be an important consideration when evaluating animals suspected to have
      sporotrichosis. To the authors' knowledge, use of itraconazole to treat a dog
      with sporotrichosis has not been reported previously.

PMID- 11345308
TI  - Use of carboplatin for treatment of dogs with malignant melanoma: 27 cases (1989
      2000).
AB  - OBJECTIVE: To evaluate response rate and duration of malignant melanomas in dogs
      treated with carboplatin. DESIGN: Retrospective study. ANIMALS: 27 client-owned
      dogs with spontaneously occurring measurable malignant melanomas. PROCEDURE:
      Records of dogs with melanomas treated with carboplatin from October 1989 to June
      2000 were reviewed. Carboplatin was administered IV at doses of 300 or 350 mg/m2
      of body surface area. Response to treatment and evidence of drug toxicity were
      determined. RESULT: Response to treatment could be evaluated in 25 dogs. Of
      those, overall response rate was 28%. One dog had a complete response, 6 (24%)
      dogs had a partial response (> 50% reduction in tumor burden). Median duration of
      partial response was 165 days. Eighteen dogs had stable disease (n = 9; 36%) or
      progressive disease (9; 36%). Response to treatment was significantly associated
      with carboplatin dose on a milligram per kilogram basis (15.1 mg/kg 16.9 mg/lb]
      of body weight vs 12.6 mg/kg [5.7 mg/lb]). Evidence of gastrointestinal toxicosis
      could be assessed in 27 dogs. Mean body weight of 5 dogs that developed
      gastrointestinal toxicosis was significantly less than that of 22 dogs without
      gastrointestinal toxicosis (9.9 kg [21.8 lb] vs 19.3 kg [42.5 lb]). CONCLUSIONS
      AND CLINICAL RELEVANCE: Carboplatin had activity against macroscopic
      spontaneously occurring malignant melanomas in dogs and should be considered as
      an adjunctive treatment for microscopic local or metastatic tumors.
      Gastrointestinal toxicosis was associated with body weight. Because small dogs
      are more likely to have adverse gastrointestinal effects, gastrointestinal
      protectants should be considered for these patients.

PMID- 11345309
TI  - Clinical indications for use of fresh frozen plasma in dogs: 74 dogs (October
      through December 1999).
AB  - OBJECTIVE: To document reasons for use of fresh frozen plasma (FFP) in dogs and
      determine variables that apparently triggered the decision to use FFP. DESIGN:
      Retrospective study. ANIMALS: 74 dogs. PROCEDURE: Medical records of dogs that
      received FFP at a veterinary teaching hospital during a 3-month period were
      reviewed. RESULTS: The 74 dogs underwent 144 transfusion episodes (TE; a TE was
      defined as 1 day of transfusion therapy) and received 252 units (120 ml/unit) of
      FFP. Fresh frozen plasma was administered to provide coagulation factors (67 TE),
      albumin (91), alpha-macroglobulin (15), or immunoglobulins (19); for some TE,
      multiple clinical indications were identified. Variables that apparently
      triggered the decision to administer FFP included active hemorrhage with or
      without prolongation of coagulation times, low total plasma protein
      concentration, persistent vomiting associated with pancreatitis, and sepsis. Mean
      doses of FFP for each indication were between 8.5 and 9.4 ml/kg (3.9 and 4.3
      ml/lb). Small dogs were generally given higher doses (mean dose, 13.9 ml/kg [6.3
      ml/lb]) than large dogs (mean dose, 5.1 ml/kg [2.3 ml/lb]). Fifty (68%) dogs were
      alive at the time of discharge from the hospital. CONCLUSIONS AND CLINICAL
      RELEVANCE: Results suggest that FFP plays an important role in the care of
      critically ill dogs. Because the supply of FFP is limited, guidelines for when
      administration of FFP may be clinically useful should be developed.

PMID- 11345310
TI  - Comparison of results of thoracic radiography, cytologic evaluation of
      bronchoalveolar lavage fluid, and histologic evaluation of lung specimens in dogs
      with respiratory tract disease: 16 cases (1996-2000).
AB  - OBJECTIVE: To compare results of thoracic radiography, cytologic evaluation of
      bronchoalveolar lavage (BAL) fluid, and histologic evaluation of biopsy and
      necropsy specimens in dogs with respiratory tract disease and to determine
      whether histologic evaluation provides important diagnostic information not
      attainable by the other methods. DESIGN: Retrospective study. ANIMALS: 16 dogs.
      PROCEDURE: BAL fluid was classified as normal, neutrophilic, eosinophilic,
      mononuclear, mixed, neoplastic, or nondiagnostic. Radiographic abnormalities were
      classified as interstitial, bronchial, bronchointerstitial, or alveolar.
      Histologic lesions were classified as inflammatory, fibrotic, or neoplastic, and
      the predominant site of histologic lesions was classified as the alveoli,
      interstitium, or airway. RESULTS: The predominant radiographic location of
      lesions correlated with the histologic location in 8 dogs. Of 11 dogs with
      histologic evidence of inflammatory disease, 8 had inflammatory BAL fluid. Of the
      2 dogs with histologic evidence of neoplasia, 1 had BAL fluid suggestive of
      neoplasia, and the other had BAL fluid consistent with septic purulent
      inflammation. Two dogs without any histologic abnormalities had mononuclear or
      nondiagnostic BAL fluid. Two dogs with histologic evidence of fibrosis had
      mononuclear or mixed inflammatory BAL fluid. CONCLUSIONS AND CLINICAL RELEVANCE:
      Results suggest that although thoracic radiography, cytologic evaluation of BAL
      fluid, and histologic evaluation of lung specimens are complementary, each method
      has limitations in regard to how well results reflect the underlying disease
      process in dogs with respiratory tract disease. Lung biopsy should be considered
      in cases where results of radiography and cytology are nondiagnostic.

PMID- 11345311
TI  - Frequency of and risk factors for epistaxis associated with exercise-induced
      pulmonary hemorrhage in horses: 251,609 race starts (1992-1997).
AB  - OBJECTIVE: To determine the frequency of epistaxis during or after racing among
      racehorses and identify factors associated with development of epistaxis. DESIGN:
      Retrospective study. SAMPLE POPULATION: 247,564 Thoroughbred and 4,045 Anglo-Arab
      race starts. PROCEDURE: Race start information (breed, age, sex, racing distance,
      and race type) was obtained for Thoroughbred and Anglo-Arab horses racing in
      Japan Racing Association-sanctioned races between 1992 and 1997. All horses that
      raced were examined by a veterinarian within 30 minutes of the conclusion of the
      race; any horse that had blood at the nostrils was examined with an endoscope. If
      blood was observed in the trachea, epistaxis related to exercise-induced
      pulmonary hemorrhage (EIPH) was diagnosed. RESULTS: Epistaxis related to EIPH was
      identified following 369 race starts (0.15%). Frequency of EIPH-related epistaxis
      was significantly associated with race type, age, distance, and sex. Epistaxis
      was more common following steeplechase races than following flat races, in older
      horses than in horses that were 2 years old, following races < or =1,600 m long
      than following races between 1,601 and 2,000 m long, and in females than in
      sexually intact males. For horses that had an episode of epistaxis, the
      recurrence rate was 4.64%. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested
      that frequency of EIPH-related epistaxis in racehorses is associated with the
      horse's age and sex, the type of race, and the distance raced. The higher
      frequency in shorter races suggests that higher intensity exercise of shorter
      duration may increase the probability of EIPH.

PMID- 11345312
TI  - Effects of parenteral administration of doramectin or a combination of ivermectin
      and clorsulon on control of gastrointestinal nematode and liver fluke infections
      and on growth performance in cattle.
AB  - OBJECTIVE: To compare effects of an injectable doramectin preparation with those
      of an injectable ivermectin-clorsulon preparation on control of gastrointestinal
      nematodes and liver flukes and on growth performance in cattle. DESIGN:
      Randomized complete block design. ANIMALS: 60 crossbred calves. PROCEDURES:
      Calves (20/treatment group) were treated with doramectin or ivermectin-clorsulon
      or were not treated. Fecal samples were collected for nematode and Fasciola
      hepatica egg counts on day 0 and for up to 140 days after treatment. Cattle were
      weighed before treatment and at 28-day intervals until day 140. RESULTS: From day
      7 through day 49, nematode egg counts for calves treated with doramectin or with
      ivermectin-clorsulon were significantly lower than those for untreated control
      calves. As the study progressed beyond day 56, the percentages of cattle with
      fluke eggs in their feces increased, but differences in regard to these
      percentages were not detected among the 3 groups. Average daily gain for the
      doramectin-treated cattle (0.79 kg/d [1.74 lb/d]) was significantly greater than
      that for the cattle treated with ivermectin-clorsuIon (0.71 kg/d [1.56 lb/d]);
      values for both groups were significantly greater than that for the control
      cattle (0.62 kg/d [1.37 lb/d]). CONCLUSIONS AND CLINICAL RELEVANCE: Results
      suggest that doramectin had a greater impact on subclinical gastrointestinal
      tract parasitism in calves, as demonstrated by growth performance, than did
      ivermectin-clorsulon. In the Gulf Coast region of the United States, spring-born
      nursing beef calves may have minimal grazing exposure to F hepatica during the
      peak fluke transmission period; therefore, mature fluke burdens may be negligible
      at the beginning of the fall season.

PMID- 11345313
TI  - Response to and efficacy of vaccination against eastern equine encephalomyelitis
      virus in emus.
AB  - OBJECTIVE: To evaluate humoral immune responses of emus vaccinated with
      commercially available equine polyvalent or experimental monovalent eastern
      equine encephalomyelitis (EEE) virus and western equine encephalomyelitis (WEE)
      virus vaccines and to determine whether vaccinated emus were protected against
      challenge with EEE virus. DESIGN: Cohort study. ANIMALS: 25 emus. PROCEDURE:
      Birds were randomly assigned to groups (n = 5/group) and vaccinated with 1 of 2
      commercially available polyvalent equine vaccines, a monovalent EEE virus
      vaccine, or a monovalent WEE virus vaccine or were not vaccinated. Neutralizing
      antibody responses against EEE and WEE viruses were examined at regular intervals
      for up to 9 months. All emus vaccinated with the equine vaccines and 2
      unvaccinated control birds were challenged with EEE virus. An additional
      unvaccinated bird was housed with the control birds to assess the possibility of
      contact transmission. RESULTS: All 4 vaccines induced detectable neutralizing
      antibody titers, and all birds vaccinated with the equine vaccines were fully
      protected against an otherwise lethal dose of EEE virus. Unvaccinated challenged
      birds developed viremia (> 10(9) plaque-forming units/ml of blood) and shed virus
      in feces, oral secretions, and regurgitated material. The unvaccinated pen-mate
      became infected in the absence of mosquito vectors, presumably as a result of
      direct virus transmission between birds. CONCLUSIONS AND CLINICAL RELEVANCE:
      Results indicate that emus infected with EEE virus develop a high-titer viremia
      and suggest that they may serve as important virus reservoirs. Infected emus shed
      EEE virus in secretions and excretions, making them a direct hazard to pen-mates
      and attending humans. Commercially available polyvalent equine vaccines protect
      emus against EEE virus infection.

PMID- 11345315
TI  - AFLP fingerprinting for assessing intraspecific variation and genome mapping in
      mites.
AB  - Molecular genetic techniques have come a long way in the last decade. With the
      advent of PCR, genetic markers are now accessible for all organisms, including
      mites. However, there is usually a trade-off between the accuracy of the
      molecular technique or genetic marker and expediency. In mites, many molecular
      techniques are not applicable due to their small size. Here we describe a
      relatively new molecular fingerprinting technique, amplified fragment length
      polymorphism (AFLP), which is currently used widely in plant genomic research. We
      outline the AFLP procedure adapted for mites, show results using this technique
      from our own research and discuss the benefits and limitations of AFLPs for
      assessing genetic variation and for genome mapping. It is our intention to
      highlight the possible use of AFLPs as genetic markers with a broad application
      in acarological research.

PMID- 11345314
TI  - The application of molecular markers in the study of diversity in acarology: a
      review.
AB  - The application of molecular markers to the study of ticks and mites has recently
      yielded new insights into their population structures and taxonomic
      relationships. Ticks have been studied at individual, population and species
      level. Mites are a more diverse group and those that have been studied to the
      same degree as the ticks include the Tetranychidae (spider mites), Phytoseiidae
      (predatory mites) and the Eriophyidae. Population variation has also been studied
      in the important bee parasitic mite Varroa jacobsoni Oudemans. The methods used
      to study these organisms have much in common. At the individual level these range
      from general approaches, such as AFLP, RAPD or DALP, to highly specific
      microsatellite analysis. Although these markers also work at the population and
      species level, additional analysis of specific nuclear or mitochondrial genes has
      been conducted either by RFLP or sequencing. Molecular applications have had
      particular success in facilitating the identification of taxonomically difficult
      species, understanding population structures and elucidating phylogenetic
      relationships.

PMID- 11345316
TI  - Isolation and characterization by direct amplification of length polymorphisms
      (DALP) of codominant genetic markers with Mendelian inheritance in Neoseiulus
      californicus (Acari: Phytoseiidae).
AB  - We report the first application of a new method designed to isolate polymorphic
      loci in any organism, the direct amplification of length polymorphism. Five
      polymorphic loci were readily isolated in the predatory mite Neoseiulus
      californicus (Acari: Phytoseiidae). Two to five alleles were identified among 46
      isofemale lines based on fragment size variation due to micro
      deletions/insertions. Genotyping F1 and F2 progenies from controlled
      heterogametic crosses and backcrosses allowed to establish the Mendelian
      inheritance of these alleles, their codominance, and pairwise recombination
      rates. Nucleotidic sequence divergence due to single base substitution was also
      found in the flanking regions of the polymorphism. We discuss the usefulness of
      these markers in studies of reproductive systems as well as population genetics,
      in particular, in mite species where the amount of DNA or richness in
      microsatellites could be limiting factors in the isolation of polymorphic loci.

PMID- 11345317
TI  - A preliminary assessment of the utility of elongation factor-1alpha in
      elucidating relationships among basal Mesostigmata.
AB  - Phylogenetic relationships in the Mesostigmata are assessed using DNA sequence
      data for a segment of the elongation factor-1alpha gene. This is the first
      application of this nuclear protein coding gene to problems of higher
      relationships in Parasitiformes. Initial testing revealed extensive variability
      in nucleotide and corresponding amino acid sequences, both among and within
      mesostigmatid infraorders. However, accuracy, as assessed by the ability of these
      data to recover well-supported taxa, was inconsistent for all analyses using
      unweighted data. None of these analyses consistently recovered Mesostigmata,
      although less inclusive taxa, such as Uropodina and Trigynaspida, were often
      recovered. Accuracy was highest for an analysis using applied weighting on the
      nucleotide sequence data. The overall results provide support for monophyly of
      Uropodina, Trigynaspida, and a grouping of Zerconina, Parasitina, and
      Dermanyssina, and suggest close relationships between Heterozerconina and Sejina.

PMID- 11345318
TI  - Interspecific diversity of mitochondrial COI sequences in Japanese Panonychus
      species (Acari: Tetranychidae).
AB  - Sequences of a part of the mitochondrial cytochrome oxidase subunit I (COI) gene
      were analyzed in four Japanese Panonychus species to determine their phylogenetic
      relationships. Neighbor-Joining and maximum likelihood analysis resulted in a
      high bootstrap support of the relationships within the genus Panonychus. In
      contrast with a previous study based on ribosomal DNA data, the COI phylogeny
      suggested that P. mori was more distantly related to P. citri than to P. ulmi.
      This study shows for the first time that P. osmanthi is closely related to P.
      citri. Intraspecific variation analysis shows that the genetic distance between
      two local populations of P. mori is higher than between P. citri and P. osmanthi.

PMID- 11345319
TI  - Gall mite molecular phylogeny and its relationship to the evolution of plant host
      specificity.
AB  - The phylogenetic relationships of all seven known species of Cecidophyopsis mites
      (Acari: Eriophyidae) with Ribes hosts have been inferred from ribosomal DNA
      sequences. This analysis found groups of closely related mites. The five gall
      forming species, four of which are monophagous and one which has two hosts, were
      found in two groups. Another group consisted of the two non gall-forming species,
      one of which has two hosts, while the other is monophagous. The molecular
      phylogeny of their known Ribes host plants was calculated using the equivalent
      ribosomal regions as the mites. The structure of the two trees (mites vs hosts)
      was clearly different, implying that mite speciation did not closely follow
      speciation events in the plant hosts. Instead, the three groups of Ribes
      infesting Cecidophyopsis mites have derived from a common galling ancestor
      millions of years ago. Each mite group has recently diversified onto different
      primary hosts. One group of mites has also lost the galling habit. The results
      have implications for host range changes and the durability of mite-resistance
      genes in cultivated Ribes.

PMID- 11345320
TI  - Species and strain identification of the predatory mite Euseius finlandicus by
      RAPD-PCR and ITS sequences.
AB  - The variation within and between Finnish Euseius finlandicus populations was
      investigated by RAPD-PCR and ITS sequence analyses. Resin DNA extraction was
      found to be a suitable method for samples of single mites used in PCR. The
      banding patterns from 24 RAPD primers and 10 primer pairs were very similar and
      reproducible in all specimens of the predatory mite studied. However, the E.
      finlandicus K-strain could be distinguished from organophosphate-resistant
      predatory mites (R-strain), since almost all of them produced a 1,400 bp RAPD-PCR
      product, which was missing or very rare in other strains studied. Another RAPD
      band of ca. 680 bp was in turn much more common in other mites of E. finlandicus
      than in the K-strain mites. Mite specific primers were designed and used to
      follow the survival of the R-strain released on apple trees. The 680 bp band
      obtained with specific primers was specific to the species E. finlandicus mites
      studied, including those that had been negative with RAPD primers. The 1,400 bp
      specific primers could be used as a marker for following the survival of R-strain
      mites on apple trees. At the species level it was possible to distinguish adults
      and eggs of E. finlandicus from Anthoseius rhenanus and Phytonemus pallidus by
      RAPD-PCR. In addition, a band at 480bp was found to correspond to DNA of the
      predatory mite Phytoseius macropilis, when both specific primer pairs were used
      together. It was not possible to amplify the ITS region of E. finlandicus rDNA
      using several primer pairs that work in other mites and aphids. However, a
      basidiomycete rDNA sequence was amplified with one of these ITS primer pairs in K
      strain mites. Finally, it was found that fungal rDNA-specific primers amplified
      an ITS region of ca. 650 bp in several strains of E. finlandicus. Internal
      primers, designed to amplify the central part of the 650 bp product, successfully
      amplified this product from all the mites.

PMID- 11345321
TI  - Out of Africa: origins of the Taenia tapeworms in humans.
AB  - Phylogenetic and divergence date analyses indicate that the occurrence of Taenia
      tapeworms in humans pre-dates the development of agriculture, animal husbandry
      and domestication of cattle (Bos spp.) or swine (Sus scrofa). Taeniid tapeworms
      in Africa twice independently colonized hominids and the genus Homo prior to the
      origin of modern humans. Dietary and behavioural shifts, from herbivory to
      scavenging and carnivory, as early Homo entered the carnivore guild in the
      Pliocene/Pleistocene, were drivers for host switching by tapeworms to hominids
      from carnivores including hyaenids and felids. Parasitological data provide a
      unique means of elucidating the historical ecology, foraging behaviour and food
      habits of hominids during the diversification of Homo spp.

PMID- 11345322
TI  - Gametic incompatibilities between races of Drosophila melanogaster.
AB  - Reproductive-isolating mechanisms between nascent species may involve sperm-egg
      recognition and have been best described in externally fertilizing organisms
      where such recognition is essential in preventing undesirable fertilizations.
      However, reproductive barriers in internally fertilizing species differ in
      significant ways, and a direct role for sperm-egg interactions has yet to be
      demonstrated. Females of many strains of Drosophila melanogaster from Zimbabwe,
      Africa, do not mate readily with cosmopolitan males. This polymorphism in mate
      choice is postulated to represent incipient speciation. We now report that, in
      one direction, crosses between the above populations produce far fewer offspring
      than reciprocal crosses due to a lower rate of egg hatch. We established that egg
      inviability in these crosses was due to defects in fertilization. Thus, even in
      taxa with internal fertilization, gametic incompatibility may be a mechanism
      relevant to reproductive isolation during incipient speciation.

PMID- 11345323
TI  - Female body odour is a potential cue to ovulation.
AB  - Human body odours have been reported to influence female mate choice. Women
      prefer the odours of immunocompatible men and, during their fertile period, judge
      the body odours of men with symmetrical bodies--which is indicative of genetic
      quality--as sexy and pleasant. The reproductive success of men largely depends on
      mating with fertile women, but it is not known whether men can detect a woman's
      fertile period. We asked women who had regular menstrual cycles and who were not
      using hormonal contraceptives to wear a T-shirt for three consecutive nights
      during their late follicular (ovulatory) phase and another T-shirt during the
      luteal (non-ovulatory) phase of their menstrual cycle. Male raters judged the
      odours of T-shirts worn during the follicular phase as more pleasant and sexy
      than odours from T-shirts worn during the luteal phase. The odour differences
      between the follicular and luteal phases did not dissipate quickly over time as
      male raters were able to detect and judge follicular phase body odours as more
      pleasant and sexy than the odours from the luteal phase even after the T-shirts
      were kept at room temperature for one week. These findings suggest that ovulation
      may not be concealed and that men could use ovulation-linked odours in their mate
      selection.

PMID- 11345324
TI  - Microsatellites reveal high levels of population substructuring in the species
      poor Eretmodine cichlid lineage from Lake Tanganyika.
AB  - This study investigated fine-scale population substructuring in an apparently
      monogamous, biparental mouth-brooding cichlid. Microsatellite allele frequencies
      were determined at four polymorphic loci for nine populations of Eretmodus
      cyanostictus. We provide empirical support for the hypothesis that a species
      employing this breeding strategy should exhibit high levels of population
      substructuring. Stretches of sand represent considerable barriers to dispersal
      and, in contrast to the rock-dwelling cichlids of Lake Malawi, distance alone,
      along a continuous rocky shoreline, is sufficient to reduce gene flow
      significantly There was a significant pattern of isolation by distance both along
      the whole study area and over the stretch of continuous shoreline, suggesting
      that this species has poor dispersal capabilities and that juveniles establish
      territories close to their natal site. Despite limited dispersal, E. cyanostictus
      populations are not significantly more inbred than a more-widely dispersing rock
      dwelling cichlid from Lake Malawi. This finding may cast doubt on the hypothesis
      that polyandry has evolved as a mechanism for maintaining genetic diversity in
      Lake Malawi cichlids. High levels of substructuring may not always promote high
      levels of speciation, and other factors, such as the intensity of sexual
      selection, may be more important in determining the speciation potential of a
      lineage.

PMID- 11345326
TI  - Growth patterns in euconodont crown enamel: implications for life history and
      mode-of-life reconstruction in the earliest vertebrates.
AB  - Euconodonts were the first vertebrates to produce a mineralized skeleton. It is
      concluded that the minor increments in the crown enamels of Protopanderodus
      varicostatus and Drepanodus robustus are probable homologues of the cross
      striations in hominoid enamel, although they are much more variable in thickness
      and represent daily to weekly growth. Major increments are superficially similar
      to lines of Retzuis, but represent a check in growth that is likely to have
      occurred at monthly intervals. Periods of above- and below-average growth are
      likely to have been seasonally moderated. The growth of P. varicostatus' elements
      are characterized by two distinct phases: the production of a triangular,
      asymmetrical juvenile 'proto-element' followed, in a second phase, by the
      development of the curved and twisted geometry of the adult element. These
      fundamentally different morphologies imply that juvenile and adult animals had
      different modes of life and/or feeding strategies. In these animals the growth of
      the elements was indeterminate. The growth model for euconodonts is clearly
      different from that of hominoid teeth as the enamel organ must have reformed
      repeatedly throughout life.

PMID- 11345325
TI  - Glacial survival of the Norwegian lemming (Lemmus lemmus) in Scandinavia:
      inference from mitochondrial DNA variation.
AB  - In order to evaluate the biogeographical hypothesis that the Norwegian lemming
      (Lemmus lemmus) survived the last glacial period in some Scandinavian refugia, we
      examined variation in the nucleotide sequence of the mitochondrial control region
      (402 base pairs (bp)) and the cytochrome b (cyt b) region (633 bp) in Norwegian
      and Siberian (Lemmus sibiricus) lemmings. The phylogenetic distinction and cyt b
      divergence estimate of 1.8% between the Norwegian and Siberian lemmings suggest
      that their separation pre-dated the last glaciation and imply that the Norwegian
      lemming is probably a relic of the Pleistocene populations from Western Europe.
      The star-like control region phylogeny and low mitochondrial DNA diversity in the
      Norwegian lemming indicate a reduction in its historical effective size followed
      by population expansion. The average estimate of post-bottleneck time (19-21 kyr)
      is close to the last glacial maximum (18-22 kyr BP). Taking these findings and
      the fossil records into consideration, it seems likely that, after colonization
      of Scandinavia in the Late Pleistocene, the Norwegian lemming suffered a
      reduction in its population effective size and survived the last glacial maximum
      in some local Scandinavian refugia, as suggested by early biogeographical work.

PMID- 11345327
TI  - State-dependent sentinels: an experimental study in the Arabian babbler.
AB  - Natural patterns of cooperative sentinel behaviour in Arabian babblers, Turdoides
      squamiceps, have proven consistent with state-dependent models of individually
      selfish anti-predator strategies. Here we demonstrate experimentally that
      sentinel effort within groups is determined simply by individual state. The two
      highest-ranking males in eight groups were separately fed a supplement of
      mealworms, each for one day at a time. Control days before and after each
      treatment confirmed that no carry-over effects occurred, and that most normal
      sentinel activity was carried out by alpha males, then beta males and then by the
      rest of the group. When supplemented, both alpha and beta males exhibited similar
      marked increases in sentinel activity, relative to control days. Unsupplemented
      males and the rest of the group incompletely compensated for these increases with
      reductions in sentinel effort. Differences in individual body mass within groups
      reflected natural and experimental variation in sentinel effort. Alpha and beta
      males weighed more than other group members, and gained mass only when
      supplementally fed. There was no evidence either for competitive sentinel
      behaviour, nor for any increased interference between males during the
      supplementation treatments. These results therefore provide strong evidence in
      support of the state-dependent approach to cooperative sentinel behaviour.

PMID- 11345328
TI  - Ignorant hooded crows follow knowledgeable roost-mates to food: support for the
      information centre hypothesis.
AB  - Communal roosting in birds may function to enhance foraging efficiency as
      explained by the information centre hypothesis, which predicts that successful
      foragers return from the roost to the rewarding food patch and that birds
      ignorant of this food follow knowledgeable roost-mates. We tested these
      predictions by exposing 34 radio-tagged, free-ranging, flock-living hooded crows
      (Corvus corone cornix) to a novel experimental set-up mimicking a superfluous
      food patch with maximum temporal and spatial unpredictability Each replicate
      lasted two days and was located on a new site. Data were collected during ten
      replicates over three years. First, a crow was more likely to visit the
      experimental food patch on the second day when it had been there on the first
      day. Second, when a crow had not been at this food patch on the first day, it was
      more likely to visit it on the second day if it had roosted together with a crow
      that had been there on the first day, but only if this knowledgeable roost-mate
      returned to the food patch on the second day. Our results support the information
      centre hypothesis and suggest that communal roosting might function to enhance
      foraging efficiency in hooded crows.

PMID- 11345329
TI  - Sex, bowers and brains.
AB  - Inter- and intraspecific variations in the sizes of specific avian brain regions
      correspond to the complexity of the behaviour that they govern. However, no study
      has demonstrated a relationship between gross brain size and behavioural
      complexity, a hypothesis that has been proposed to explain the unusually large
      human brain. I show, using X-rays of museum specimens, that species of bowerbirds
      that build bowers have relatively larger brains than both related and
      ecologically similar but unrelated species that do not build bowers. Bower design
      varies across species from simple cleared courts to ornate, hut-like structures
      large enough to contain a small child. Furthermore, species building more complex
      bowers have relatively larger brains, both within each of the two different bower
      building clades and across the family as a whole, controlling for phylogeny. Such
      gross differences in brain size are surprising and may reflect the range of
      cognitive processes necessary for successful bower building, The relationships
      are strongest for males, the bower-building sex, although there is a similar
      trend in females. Because the size and complexity of bower design is targeted by
      female choice, the observation that relative brain size is related to bower
      complexity suggests that sexual selection may drive gross brain enlargement.

PMID- 11345330
TI  - Maternal androgens in black-headed gull (Larus ridibundus) eggs: consequences for
      chick development.
AB  - We tested the hypothesis that mother birds counterbalance the negative effects of
      hatching asynchrony for later-hatched chicks by increasing the yolk androgen
      concentrations in consecutive eggs of their clutch. In doing so, they may
      adaptively tune each offspring's competitive ability and, thus, growth and
      survival. However, evidence in support of this hypothesis is contradictory. The
      yolk concentrations of maternal androgens in the eggs of black-headed gulls
      increase significantly with the laying order of the eggs in a clutch. We
      experimentally tested the functional consequences of this increase on chick
      development under natural conditions by injecting eggs with either an oil or
      androgen solution. We created experimental clutches in which androgen levels
      either stayed constant or increased with laying order while controlling for
      differences in egg quality by using only first-laid eggs. We then compared
      development, growth and survival between these broods. Androgen treatment
      enhanced embryonic development because androgen-treated eggs hatched half a day
      earlier than controls, while their size at hatching was similar to oil-treated
      controls. Androgen treatment did not increase chick survival, but it enhanced
      growth. Androgen-treated, third-hatched chicks had a higher body mass and longer
      legs than third-hatched chicks that hatched from oil-treated eggs. At the same
      time, growth of first chicks (which were all oil treated) was reduced by the
      presence of two androgen-treated siblings, suggesting that yolk androgens enhance
      the competitive ability of later-hatched chicks. Our results support the
      hypothesis that transfer of different amounts of androgens to the eggs of a
      clutch is a mechanism by which mothers maximize their reproductive output.

PMID- 11345331
TI  - The dependence of viral parameter estimates on the assumed viral life cycle:
      limitations of studies of viral load data.
AB  - Estimation of viral parameters, such as the basic reproductive number (R0) and
      infected cell life span, is central to the quantitative study of the within-host
      dynamics of viral diseases such as human immunodeficiency virus, hepatitis B or
      hepatitis C. As these parameters can rarely be determined directly, they are
      usually estimated indirectly by fitting mathematical models to viral load data.
      This paper investigates how parameter estimates obtained by such procedures
      depend on the assumptions made concerning the viral life cycle. It finds that
      estimates of the basic reproductive number obtained using viral load data
      collected during the initial stages of infection can depend quite sensitively on
      these assumptions. The use of models which neglect the intracellular delay before
      virion production can lead to severe underestimates of R0 and, hence, to overly
      optimistic predictions of how efficacious treatment must be in order to prevent
      or eradicate the disease. These results are also of importance for attempts at
      estimating R0 from similar epidemiological data as there is a correspondence
      between within-host and between-host models. Estimates of the life span of
      infected cells obtained from viral load data collected during drug treatment
      studies also depend on the assumptions made in modelling the virus life cycle.
      The use of more realistic descriptions of the life cycle is seen to increase
      estimates of infected cell life span, in addition to providing a new explanation
      for the shoulder phase seen during drug treatment. This study highlights the
      limitations of what can be learnt by fitting mathematical models to infectious
      disease data without detailed independent knowledge of the life cycle of the
      infectious agent.

PMID- 11345332
TI  - Transfection of Wolbachia in Lepidoptera: the feminizer of the adzuki bean borer
      Ostrinia scapulalis causes male killing in the Mediterranean flour moth Ephestia
      kuehniella.
AB  - Two species of Lepidoptera, Ostrinia scapulalis and Ephestia kuehniella, harbour
      Wolbachia, which are maternally transmitted intracellular bacteria that often
      cause reproductive abnormalities in arthropods. While the infection in O.
      scapulalis causes conversion of genetic males into functional females
      (feminization), that in E. kuehniella induces cytoplasmic incompatibility. In the
      present study, we investigated the relative importance of host and Wolbachia
      factors in the differential expression of reproductive alterations in these
      insects. We transferred the Wolbachia harboured by O. scapulalis to E. kuehniella
      in which the original infection had been cured by tetracycline treatment. The
      transfected strain of E. kuehniella expressed a maternally inherited, female
      biased sex ratio. Unexpectedly, two lines of evidence suggested that the sex
      ratio distortion was due to male killing. First, higher mortality of young larvae
      was observed. Second, the removal of the transferred Wolbachia resulted in the
      recovery of a 1:1 sex ratio, whereas the removal of a feminizer should result in
      a male-biased sex ratio among offspring. To the authors' knowledge, this is the
      first report that a single Wolbachia strain can cause two distinct sexual
      abnormalities in different hosts. Our observations highlighted the importance of
      host-Wolbachia interactions in determining the phenotype of reproductive
      alterations.

PMID- 11345333
TI  - Asymmetrical crossing barriers in angiosperms.
AB  - Patterns of reproductive isolation between species may provide insight into the
      mechanisms and evolution of barriers to interspecific gene exchange. We used data
      from published interspecific hybridization experiments from 14 genera of
      angiosperms in order to test for the presence of asymmetrical barriers to gene
      exchange. Reproductive isolation was examined at three life-history stages: the
      ability of interspecific crosses to produce seeds, the viability of F1 hybrids,
      and the fertility of F1 hybrids. Statistically significant asymmetries in the
      strength of reproductive isolation between species were detected in all genera
      and at each of the three life-history stages. Asymmetries in seed production may
      be caused by a variety of mechanisms including differences in stigma/style
      lengths, self compatibility and differential fruit abortion. Asymmetries in post
      zygotic isolation are probably caused by nuclear-cytoplasmic interactions.
      Asymmetrical reproductive isolation between plant taxa may have important
      implications for the dynamics of hybrid zones, the direction of genetic
      introgression and the probability of reinforcement.

PMID- 11345334
TI  - Transient dynamics and food-web complexity in the Lotka-Volterra cascade model.
AB  - How does the long-term behaviour near equilibrium of model food webs correlate
      with their short-term transient dynamics? Here, simulations of the Lotka 
      Volterra cascade model of food webs provide the first evidence to answer this
      question. Transient behaviour is measured by resilience, reactivity, the maximum
      amplification of a perturbation and the time at which the maximum amplification
      occurs. Model food webs with a higher probability of local asymptotic stability
      may be less resilient and may have a larger transient growth of perturbations.
      Given a fixed connectance, the sizes and durations of transient responses to
      perturbations increase with the number of species. Given a fixed number of
      species, as connectance increases, the sizes and durations of transient responses
      to perturbations may increase or decrease depending on the type of link that is
      varied. Reactivity is more sensitive to changes in the number of donor-controlled
      links than to changes in the number of recipient-controlled links, while
      resilience is more sensitive to changes in the number of recipient-controlled
      links than to changes in the number of donor-controlled links. Transient
      behaviour is likely to be one of the important factors affecting the persistence
      of ecological communities.

PMID- 11345335
TI  - A comparative test of a theory for the evolution of anisogamy.
AB  - Why are sperm small and eggs large? The dominant explanation for the evolution of
      gamete size dimorphism envisages two opposing selection pressures acting on
      gamete size: small gametes are favoured because many can be produced, whereas
      large gametes contribute to a large zygote with consequently increased survival
      chances. This model predicts disruptive selection on gamete size (i.e. selection
      for anisogamy) if increases in zygote size confer disproportional increases in
      fitness (at least over part of its size range). It therefore predicts that
      increases in adult size should be accompanied by stronger selection for
      anisogamy. Using data from the green algal order Volvocales, we provide the first
      phylogenetically controlled test of the model's predictions using a published
      phylogeny and a new phylogeny derived by a different method. The predictions that
      larger organisms should (i) have a greater degree of gamete dimorphism and (ii)
      have larger eggs are broadly upheld. However, the results are highly sensitive to
      the phylogeny and the mode of analysis used.

PMID- 11345336
TI  - When does neural degeneration occur in diabetic retinopathy?

PMID- 11345338
TI  - Laser-induced chorioretinal venous anastomosis for non-ischaemic hemi-central
      vein occlusion.
AB  - PURPOSE: To assess the effectiveness and complications of laser-induced
      chorioretinal venous anastomosis performed on eyes with non-ischaemic hemi
      central retinal vein occlusions (hemi-CRVO). METHODS: Fourteen eyes with a hemi
      CRVO which reduced the visual acuity to 6/24 or less were treated with argon
      laser photocoagulation in an attempt to create a chorioretinal venous anastomosis
      between a retinal vein and the choroidal circulation. RESULTS: Laser anastomoses
      were successfully created in six eyes (43%) and required a mean of 1.8 attempts
      in each eye. Of the eyes that developed an anastomosis, four had significant
      visual improvement. The distal retinal venous segment closed off in five eyes and
      these had prophylactic segmental argon pan-retinal photocoagulation performed.
      Two eyes had localized fibrovascular proliferation. No permanent vision
      threatening complications were observed in any of the 14 eyes over the follow-up
      period. CONCLUSIONS: Successful anastomosis between the retinal and choroidal
      circulation in eyes with hemi-vein occlusions may reduce macular oedema and
      improve vision. Complications of the technique are significant and a randomized
      clinical trial is due to commence which may clarify the suitability of this
      treatment.

PMID- 11345337
TI  - Risk factors and significance of finding asymptomatic retinal emboli.
AB  - PURPOSE: To assess the prevalence rates for asymptomatic retinal emboli among
      both younger and older individuals, with single and multiple potential risk
      factors, in order to alert clinicians to the probability of finding retinal
      emboli in patients with varying characteristics. METHODS: In all, 3654 people
      aged 49-97 attending the Blue Mountains Eye Study had a detailed eye examination
      which included retinal photographs of the central and peripheral retinal fields.
      Retinal emboli were identified during masked photographic grading and definite
      cases were adjudicated. RESULTS: Retinal emboli were found in 51 subjects (1.4%
      of the population); these included 1.1% of people aged 49-69 years (middle-aged
      subjects) and 2.0% of people aged more than 70 years (older subjects). Risk
      factors identified were male sex, increasing age, hypertension, current smoking,
      history of any vascular event (angina, myocardial infarct, stroke) or history of
      vascular surgery. Among middle-aged subjects, current smoking and history of
      hypertension or a vascular event were significantly associated with emboli (odds
      ratios (OR) 2.3-3.1), while in older subjects, history of vascular surgery was
      related (OR 4.7). The highest prevalence of emboli (5.5%) was found in people who
      reported a history of hypertension and also smoked (OR 6.0). Among hypertensive
      men who smoked, emboli were present in 7.6%. CONCLUSIONS: This study indicates
      that although asymptomatic retinal emboli are relatively infrequent in the
      general older population, these lesions are surprisingly common in people
      (particularly men) with multiple risk factors. Ophthalmologists could routinely
      screen for emboli and consider alerting the patients' general practitioners to
      review vascular risk factors.

PMID- 11345339
TI  - Secondary haemorrhage after dacryocystorhinostomy.
AB  - OBJECTIVE: To describe the incidence, clinical features, possible risk factors
      and outcome of patients suffering secondary haemorrhage after
      dacryocystorhinostomy (DCR). METHODS: Records of all patients undergoing external
      DCR by one surgeon (AAM) over a 6-year period were analysed retrospectively.
      RESULTS: After 293 DCR operations in 260 patients, 10 patients had a secondary
      haemorrhage (one after bilateral DCR), usually between days 4 and 10 post
      operatively (mean 6.8 days). Six of the 10 were hospitalized for 2-5 days (mean
      2.8 days), all of whom had nasal packing, intravenous antibiotics and intravenous
      fluids; none required blood transfusion. Three patients had immune system
      defects, three had used non-steroidal anti-inflammatory drugs (NSAID) and four
      had no obvious risk factors. All 10 had a successful outcome following DCR
      (compared to an overall failure rate of 25/293 (8.5%): 16 anatomical and nine
      functional). CONCLUSIONS: Secondary haemorrhage after DCR was found to occur
      after 3.8% of DCR. Risk factors include being immunocompromised and taking NSAID
      prior to surgery. The haemorrhage did not adversely affect surgical outcome.

PMID- 11345340
TI  - Non-traumatic orbital haemorrhage.
AB  - PURPOSE: To establish the incidence of underlying orbital vascular anomalies, the
      presence of systemic associations and predisposing factors, the natural history
      and appropriate management of patients with non-traumatic orbital haemorrhage
      presenting in an orbital clinic. METHODS: The records of 115 patients with a
      diagnosis of non-traumatic orbital haemorrhage were reviewed with regard to
      clinical findings, investigations, management and outcome. RESULTS: Associated
      orbital vascular malformations were present in 104 patients (90%). Thirteen (11%)
      had additional or other predisposing factors (childbirth, prolonged headstands,
      hypertension or coagulopathies). Six patients (5%) had no predisposing factor.
      Acute onset painful proptosis, associated with lid swelling or a mass, was the
      most common presentation. Visual acuity was reduced in 37 patients (32%) at
      presentation. Excluding eight patients (7%) who underwent surgery for optic nerve
      compression, spontaneous resolution of the haemorrhage was complete in 62%,
      partial in 27%, while 4% had no resolution. Final visual acuity was reduced in 23
      patients (20%). CONCLUSION: The majority of bleeds are associated with some form
      of orbital vascular anomaly. Where no such anomaly can be demonstrated a search
      for an underlying systemic cause should be performed. Haemorrhages in the young
      were usually localized whereas those in older patients were diffuse. Orbital
      imaging, with a combination of computed tomography and magnetic resonance
      imaging, was helpful in the assessment of these lesions. Most bleeds are venous
      and self-limiting. Surgical intervention was rarely necessary and should be
      confined to those with optic nerve compromise or a localized lesion which
      persists.

PMID- 11345341
TI  - Retinal neurodegeneration: early pathology in diabetes.
AB  - Normal vision depends on the normal function of retinal neurons, so vision loss
      in diabetes must ultimately be explained in terms of altered neuronal function.
      However to date relatively little attention has been paid to the impact of
      diabetes on the neural retina. Instead, the focus of most research has been
      primarily on retinal vascular changes, with the assumption that they cause
      altered neuronal function and consequently vision loss. An increasing body of
      evidence suggests that alterations in neuronal function and viability may
      contribute to the pathogenic mechanisms of diabetic retinopathy beginning shortly
      after the onset of diabetes. This view arises from neurophysiological,
      psychometric, histopathological and biochemical observations in humans and
      experimental animals. The collective evidence from past and recent studies
      supports the hypothesis that neurodegeneration, together with functional changes
      in the vasculature, is an important component of diabetic retinopathy. The
      authors invite other investigators to include the neural retina as a component of
      their studies so that the pathogenesis of diabetic retinopathy can be understood
      more clearly.

PMID- 11345342
TI  - Diplopia from peribulbar ropivicaine.
AB  - PURPOSE: To report a previously undescribed side-effect of ropivicaine (Naropin)
      used in peribulbar anaesthesia. METHODS: We report nine cases identified
      prospectively with symptomatic diplopia, predominantly vertical, following
      Ropivicaine use for peribulbar anaesthesia in routine cataract surgery. These
      nine cases occurred in a 10-week period from a total of 77 patients given 7 mL
      peribulbar ropivicaine (10 mg/mL) with 750 units hyalase prior to cataract
      extraction by a single surgical team. RESULTS: None of the cases had preoperative
      ocular motility disturbances and none had superior rectus traction sutures. All
      diplopia resolved in less than 30 h. CONCLUSIONS: Ropivicaine may have a
      prolonged motor block resulting in diplopia of up to 30 h duration after
      peribulbar anaesthesia.

PMID- 11345343
TI  - Childhood optic atrophy.
AB  - PURPOSE: To determine the causes, and relative incidence of the common causes, of
      optic nerve atrophy in children under 10 years old and to compare prevalent
      aetiologies with those given in previous studies. METHODS: The Wilmer Information
      System database was searched to identify all children, diagnosed between 1987 and
      1997 with optic atrophy, who were under 10 years old at diagnosis. The medical
      records of these children were reviewed retrospectively RESULTS: A total of 272
      children were identified, Complications from premature birth were the most
      frequent aetiology of optic atrophy (n = 44, 16%); 68% of these premature infants
      having a history of intraventricular haemorrhage. Tumour was the second most
      common aetiology (n = 40, 15%). The most frequent tumour was pilocytic
      astrocytoma (50%), followed by craniopharyngioma (17%). Hydrocephalus, unrelated
      to tumour, was the third most common aetiology (n = 26, 10%). In 114 cases (42%),
      the cause of optic atrophy became manifest in the perinatal period and/or could
      be attributed to adverse events in utero. A cause was not determined in 4% of
      cases. CONCLUSIONS: In the last decade, prematurity and hydrocephalus appear to
      have become important causes of optic atrophy in childhood. This trend is
      probably the result of improved survival of infants with extremely low birth
      weight.

PMID- 11345344
TI  - Intravitreal pefloxacin therapy in postoperative endophthalmitis.
AB  - PURPOSE: To study the efficacy of intravitreal pefloxacin in the management of
      suspected bacterial endophthalmitis. METHODS: Twenty eyes with suspected
      postoperative bacterial endophthalmitis were given an intravitreal injection of
      pefloxacin (200 microg in 0.1 mL). If required the injection was repeated after
      24 h. The main parameters evaluated were visual acuity, response to intravitreal
      therapy and any complications due to intravitreal pefloxacin. RESULTS: Fourteen
      eyes (70%) responded to intravitreal pefloxacin therapy alone, while an
      additional pars plana vitrectomy was required in six eyes (30%). Nineteen eyes
      retained a visual acuity of 6/60 or better at 3 months after the initiation of
      therapy. A retinal detachment developed in one of the eyes which received
      intravitreal therapy. CONCLUSIONS: Intravitreal pefloxacin may be a useful
      aternative therapy in bacteria endophthalmitis.

PMID- 11345345
TI  - Visual function tests, eye disease and symptoms of visual disability: a
      population-based assessment.
AB  - PURPOSE: To examine associations between eye disease and tests of visual function
      with self-reported visual disability. METHODS: The Blue Mountains Eye Study is a
      cross-sectional census-based survey of eye disease in two postcode areas in the
      Blue Mountains, west of Sydney, Australia. Of 4433 eligible residents, 3654
      (82,4%) participated. Subjects had a detailed eye examination, including tests of
      visual acuity, contrast sensitivity, disability glare and visual field. Lens and
      retinal photographs were taken and graded according to standardized protocols for
      presence of cataract, early and late age-related maculopathy, glaucoma, diabetic
      retinopathy, retinal vein occlusion and other eye diseases. An interviewer
      administered questionnaire included questions about perception of visual
      disability. RESULTS: Scores on all tests of visual function significantly
      decreased with age (P < 0.0001). This decrease persisted for all tests except
      disability glare after excluding subjects with identifiable eye disease. The
      presence of one or more eye diseases was significantly associated with all (self
      reported) measures of visual disability (trouble driving at night, difficulty
      recognizing a friend across the street, reading a newspaper or recognizing detail
      on televsion): mixed cataract (cortical and nuclear, or posterior subcapsular and
      nuclear) was associated with trouble driving at night and difficulty recognizing
      a friend across the street. A 10-letter (two-line) decrease in best corrected or
      presenting visual acuity was significantly associated with all self-reported
      measures of vsual dsability, as was a two-step decrease in contrast sensitvity. A
      five-point increase in points missing in the visual field was weakly but
      significantly associated with all self-reported measures of visual disability
      except trouble driving at night. CONCLUSIONS: Visual function declines with age.
      Impaired visual function was strongly, and eye disease relatively weakly
      associated with reports of visual disability.

PMID- 11345346
TI  - Vitreal macrophages express vascular endothelial growth factor in oxygen-induced
      retinopathy.
AB  - PURPOSE: The possibility of vitreal macrophages playing an angiogenic role in
      oxygen-induced retinopathy (OIR) was investigated. Oxygen-induced retinopathy was
      produced in newborn animals with the purpose of modeling the proliferative phase
      of human retinopathy of prematurity (ROP). MATERIALS AND METHODS: To produce OIR
      in neonatal mice, litters at postnatal day 7 were placed in 80-90% oxygen for a
      period of 5 days and then returned to room air. Pups were killed on days 7, 12,
      15, 17 and 20 over the postnatal period and were perfusion-fixed using a saline
      wash-out, followed by 4% paraformaldehyde and then India Ink. Eyes were
      enucleated and either whole-mounted, or snap-frozen and cryosectioned.
      Immunostaining procedures were used to visualize macrophages and vascular
      endothelial growth factor (VEGF) protein. The primary antibodies used were anti
      F4/80 and antimouse VEGF, respectively. Vitreal macrophages closely associated
      with the vitreo-retinal interface (within 25 microm of the inner limiting
      membrane) were counted. In situ hybridization procedures were used to analyse for
      the presence of VEGF mRNA transcript in vitreal macrophages. RESULTS: Macrophage
      numbers were found to significantly increase (P < 0.05) in eyes from oxygen
      treated animals compared with those from age-matched controls. A close spatial
      relationship was observed between macrophages and vitreal neovascular sprouts. In
      addition, vitreal macrophages were also found to transcribe and express VEGF in
      the oxygen-treated animals during the vasoproliferative phase. CONCLUSIONS: Our
      results raise the possibility that vitreal macrophages play a role in the
      pathogenesis of OIR and by inference, ROP.

PMID- 11345347
TI  - Corneal transmissibility of diode versus argon lasers and their photothermal
      effects on the cornea and iris.
AB  - PURPOSE: Diode laser (810 nm) may possess theoretical advantages over the argon
      blue-green laser (488 nm) for iridotomy/iridoplasty in an eye with oedematous
      cornea, such as the acute angle-closure glaucoma (AACG) patient, because of
      better diode laser tissue penetration in opaque media. We assessed the
      transmissibility of diode and argon lasers through corneas of varying clarity and
      evaluated the histopathological features of cornea and iris burns produced by
      these lasers. METHODS: The transmission of diode and argon lasers through human
      donor corneal buttons of three grades of clarity--clear, intermediate, and hazy-
      were compared. Corneal buttons of these varying levels of clarity were also
      treated with argon and diode lasers, with the beams deliberately focused onto the
      mid-stroma to assess their photothermal effects. Exposed pigmented irides from
      whole human eyes were treated directly with argon and diode lasers. The lasers
      were delivered via slit-lamp systems and the energy settings used were 1000 mW
      for argon and 980 mW for diode; spot sizes for both lasers were 100 microm, with
      exposure durations of 0.1 s. Light microscopy studies of these tissues were
      performed. RESULTS: Transmissibility of diode laser in clear, intermediate, and
      hazy corneas were 89, 87 and 85% respectively and was significantly superior to
      argon laser (78, 73 and 70% respectively; P < 0.001, paired Student's t-test).
      Diode laser did not produce morphological changes in all three grades of corneas
      whereas argon-laser-treated hazy corneas showed photothermal damage. Both lasers
      produced deep iris burns, with the diode laser tending to produce deeper burns.
      CONCLUSION: Our findings suggest that diode laser may be the ideal laser for
      iridotomy/iridoplasty in the AACG patient with hazy cornea.

PMID- 11345348
TI  - Corneal endothelial cell nuclei are damaged after DNA transfer using a gene gun.

PMID- 11345349
TI  - Corynebacterium pseudodiphtheriticum keratitis and conjunctivitis: a case report.
AB  - A case of keratitis and conjunctivitis in an 86-year-old man caused by
      Corynebacterium pseudodiphtheriticum is reported. Corynebacteria are uncommon
      causes of ocular surface infections. However, the presence of corneal and
      conjunctival epithelial defects in an immunocompromised patient can result in
      severe infection by a commensal organism such as C. pseudodiphtheriticum. The
      significance of a positive culture in these settings should not be overlooked.

PMID- 11345350
TI  - Hypovitaminosis A in metropolitan Adelaide.
AB  - Hypovitaminosis A is a well-recognized condition in many developing countries.
      However, in the developed world the diagnosis is frequently missed or delayed
      because of its rarity. A 67-year-old man from metropolitan Adelaide presented to
      us with gradual but severe bilateral visual loss. He had marked punctate
      epithelial keratopathy in both eyes. Hypovitaminosis was suspected because of his
      bizarre dietary habit, and this was confirmed by a combination of impression
      cytology of the ocular surface and biochemical testing of his venous blood. His
      vision responded dramatically to vitamin A supplementation. Hypovitaminosis A
      should be suspected in severe cases of 'dry-eye', especially in those patients
      with unusual dietary habit or malabsorption.

PMID- 11345351
TI  - Orbital granulomatous giant cell myositis: a case report and review.
AB  - To present a case of orbital granulomatous giant cell myositis and review the
      literature. We describe the case of a 51-year-old woman, with a past history of
      melanoma, who presented with an acutely painful orbital myositis. This evolved
      into a chronic relapsing process involving multiple muscles bilaterally; which
      demonstrated partial steroid responsiveness. Biopsy revealed a granulomatous
      giant cell myositis. Orbital granulomatous giant cell myositis is a rare
      histological entity which has an association with giant cell myocarditis and
      underlying malignancy.

PMID- 11345352
TI  - Bilateral inferior insertion of lateral rectus muscles associated with
      schizencephaly.
AB  - A 5-year-old boy with a large V-pattern exotropia is described. He has a
      background of congenital left hemiparesis associated with schizencephaly. At the
      time of surgery the lateral recti were found to be abnormally inferiorly
      positioned. Accordingly, both lateral rectus muscles were recessed 6.5 mm and
      supraplaced. A V-pattern exotropia persisted postoperatively with clinical
      overaction of the inferior obliques. To our knowledge this is the first known
      case of extraocular muscle abnormalities associated with schizencephaly.

PMID- 11345353
TI  - Use of the nerve fibre analyser after occipital cortical infarcts.

PMID- 11345354
TI  - Cataract intervention in the developing world: knock-on development through
      mentoring hospitals.

PMID- 11345355
TI  - Uniocular macular oedema and reduced vision in a patient with uveitis.

PMID- 11345356
TI  - Endothelin receptor antagonists in congestive heart failure: a new therapeutic
      principle for the future?
AB  - Congestive heart failure (CHF) is characterized by impaired left ventricular
      function, increased peripheral and pulmonary vascular resistance and reduced
      exercise tolerance and dyspnea. Thus, mediators involved in the control of
      myocardial function and vascular tone may be involved in its pathophysiology. The
      family of endothelins (ET) consists of four closely related peptides, ET-1, ET-2,
      ET-3 and ET-4, which cause vasoconstriction, cell proliferation and myocardial
      effects through activation of ETA receptors. In contrast, endothelial ETB
      receptors mediate vasodilation via release of nitric oxide and prostacyclin. In
      addition, ETB receptors in the lung are a major pathway for the clearance of ET-1
      from plasma. Thus, infusion of an ETA-receptor antagonist into the brachial
      artery in healthy humans leads to vasodilation, whereas infusion of an ETB
      receptor antagonist causes vasoconstriction. Endothelin-1 plasma levels are
      elevated in CHF and correlate both with hemodynamic severity and symptoms. Plasma
      levels of ET-1 and its precursor, big ET-1, are strong independent predictors of
      death after myocardial infarction as well as in CHF. Endothelin-1 contributes to
      increased systemic and pulmonary vascular resistance, vascular dysfunction,
      myocardial ischemia and renal impairment in CHF. Selective ETA, as well as
      combined ETA/B-receptor antagonists, have been studied in patients with CHF, and
      their use has shown impressive hemodynamic improvement (i.e., reduced peripheral
      vascular and pulmonary resistance as well as increased cardiac output). These
      results indicate that ET-receptor antagonists, indeed, have a potential to
      improve hemodynamics, symptoms and, potentially, prognosis in patients with CHF,
      which still carries a high mortality.

PMID- 11345357
TI  - Electron beam tomography and National Cholesterol Education Program guidelines in
      asymptomatic women.
AB  - OBJECTIVES: This investigation was designed to determine the relationship between
      National Cholesterol Education Program (NCEP) ATP-II lipid guidelines and
      subclinical atherosclerosis, defined by electron beam tomography (EBT) calcified
      coronary plaque, in asymptomatic women. BACKGROUND: NCEP guidelines are used to
      identify women at increased risk for coronary artery disease (CAD) on the basis
      of low density lipoprotein cholesterol (LDLC) and high density lipoprotein
      cholesterol (HDLC) values. The relationship of the guidelines to subclinical
      atherosclerosis is unknown. METHODS: A total of 304 asymptomatic women underwent
      lipid and EBT evaluation and were classified as: 1) NCEP higher risk, with LDLC >
      or =130 mg/dl and/or HDLC <35 mg/dl, or lower risk with LDLC <130 mg/dl and HDLC
      > or =35 mg/dl; and 2) EBT+ if any calcified plaque was noted or EBT- if there
      was no calcified plaque. RESULTS: Forty-two percent of patients were EBT+, with a
      mean score of 227 and percentile of 73%; 58% were EBT-. Women who were EBT+ had
      significantly higher total cholesterol, LDLC and triglycerides than EBT- women,
      but only with ages < or =55 years; women >55 years demonstrated no differences.
      NCEP higher risk women made up 53.5% of the EBT+ and 37.7% of the EBT- groups;
      NCEP lower risk women accounted for 46.5% of the EBT+ and 62.3% of the EBT-
      groups. Assuming a higher risk in subjects with EBT-defined subclinical CAD than
      in those without, only 58.6% of the total group would be correctly identified by
      NCEP guidelines as either higher or lower risk, with correct identification of
      65.5% of the younger and 52.2% of the older women. There was no correlation
      between either calcium percentile or score and any lipid measurement.
      CONCLUSIONS: This study demonstrates the shortcomings of employing NCEP
      guidelines to identify asymptomatic women with subclinical CAD, particularly
      women >55 years, and suggests increased utilization of EBT for primary prevention
      in the female population.

PMID- 11345358
TI  - Coronary calcium as a risk factor: role in global risk assessment.

PMID- 11345359
TI  - An insertion/deletion polymorphism in the alpha2B-adrenergic receptor gene is a
      novel genetic risk factor for acute coronary events.
AB  - OBJECTIVES: Our aim was to study whether an insertion/deletion (I/D) polymorphism
      in the alpha2B-adrenoceptor gene is associated with the risk for cardiovascular
      diseases. BACKGROUND: alpha2-adrenoceptors mediate contraction of vascular smooth
      muscle and induce coronary vasoconstriction in humans. The alpha2-adrenoceptor
      subtype B mediates vasoconstriction in mice. A variant of the human alpha2B
      adrenoceptor gene that encodes a D of three residues in an intracellular acidic
      motif has been shown to confer decreased receptor desensitization. This receptor
      variant could, therefore, be involved in diseases associated with enhanced
      vasoconstriction. METHODS: This study was part of a prospective population-based
      study investigating risk factors for cardiovascular diseases in a cohort of
      middle-aged men from eastern Finland. Nine hundred twelve men aged 46 to 64 years
      were followed for an average time of 4.5 years. RESULTS: In this study
      population, 192 men (21%) had the D/D genotype; 256 (28%) had the I/I genotype,
      and 464 (51%) had a heterozygous genotype. In a Cox model adjusting for other
      coronary risk factors, men with the D/D genotype had 2.2 times (95% confidence
      interval: 1.1 to 4.4, p = 0.02) the risk to experience an acute coronary event (n
      = 15 for D/D, 10 for I/I and 12 for I/D) compared with men carrying either of the
      other two genotypes. The alpha2B-adrenoceptor genotype was not associated with
      hypertension in this study population. CONCLUSIONS: The D/D genotype of the
      alpha2B-adrenoceptor is a novel genetic risk factor for acute coronary events,
      but not for hypertension.

PMID- 11345360
TI  - Obesity is independently associated with coronary endothelial dysfunction in
      patients with normal or mildly diseased coronary arteries.
AB  - OBJECTIVES: This study evaluates the impact of obesity on coronary endothelial
      function in patients with normal or mild coronary artery disease. BACKGROUND: The
      American Heart Association (AHA) has recently classified obesity as a modifiable
      risk factor for coronary heart disease. METHODS: A total of 397 consecutive
      patients with normal or mildly diseased coronary arteries at angiography
      underwent coronary vascular reactivity evaluation using intracoronary adenosine,
      acetylcholine and nitroglycerin. Patients were divided into three groups based on
      the body mass index (BMI): Group 1, patients with a BMI <25 (n = 117, normal
      weight); Group 2, patients with a BMI 25-30 (n = 149, overweight) and Group 3,
      patients with a BMI >30 (n = 131, obese). RESULTS: There were no significant
      differences among the groups in regard to other cardiovascular risk factors,
      except that overweight but not obese patients were significantly older than
      normal-weight patients (47 +/- 1 years in Group 1, 53 +/- 1 years in Group 2 and
      50 +/- 1 years in Group 3, p < 0.001). The percent change of coronary blood flow
      to acetylcholine (%delta CBF Ach) was significantly lower in the obese patients
      than in the normal-weight group (85.2 +/- 12.0% in Group 1, 63.7 +/- 10.0% in
      Group 2 and 38.1 +/- 9.6% in Group 3, p = 0.009). By multivariate analysis,
      overweight (odds ratio, 1.55; 95% confidence interval, 1.2-2.0) and obesity (odds
      ratio, 2.41; 95% confidence interval, 1.5-4.0) status were independently
      associated with impaired coronary endothelial function. CONCLUSIONS: The study
      demonstrates that obesity is independently associated with coronary endothelial
      dysfunction in patients with normal or mildly diseased coronary arteries.

PMID- 11345361
TI  - Relationship between the angiotensin-converting enzyme genotype and the forearm
      vasodilator response to estrogen replacement therapy in postmenopausal women.
AB  - OBJECTIVES: We sought to evaluate the relationship between the angiotensin
      converting enzyme (ACE) genotype and the change in forearm vasoreactivity in
      response to a three-month course of oral estrogen in postmenopausal women.
      BACKGROUND: The ACE genotype is a known predictor of the response to an ACE
      inhibitor drug; however, it is not clear whether it can modify the effect of
      estrogen replacement therapy (ERT) on endothelial function in postmenopausal
      women. METHODS: Fifty-five postmenopausal women received 0.625 mg of conjugated
      equine estrogen daily for three months. Forearm blood flow (FBF) was measured by
      strain-gauge plethysmography. RESULTS: Twenty-one, 25 and 9 patients had the
      insertion/deletion (ID), II and DD genotypes, respectively. Plasma ACE activity
      was significantly higher at baseline in patients with either the DD or ID
      genotype than in those with the II genotype (p < 0.05). A significant decrease in
      plasma ACE activity with ERT was seen in the ID and II genotypes (p < 0.05), but
      not in the DD genotype. There were no significant differences in the FBF
      responses to reactive hyperemia at baseline between the three groups. Estrogen
      replacement therapy did not alter the FBF response to reactive hyperemia in the
      DD genotype (4.0 +/- 1.3%), although ERT significantly increased the FBF response
      in the ID and II genotypes (32.6 +/- 7.5% and 30.6 +/- 6.5%, respectively; p <
      0.05). Forearm blood flow after administration of sublingual nitroglycerin did
      not change over three months in any of the three groups. CONCLUSIONS: These
      findings suggest that the effect of ERT in postmenopausal women on forearm
      endothelial function may be determined in part by the genotype of the ACE gene.

PMID- 11345363
TI  - New diagnostic criteria for diabetes and coronary artery disease: insights from
      an angiographic study.
AB  - OBJECTIVES: The goal of this research was to study coronary atherosclerosis in
      patients with type 2 diabetes compared with patients without diabetes according
      to the new definition of diabetes advocated by the American Diabetes Association
      in 1997. BACKGROUND: Patients with diabetes (fasting plasma glucose above 7.0
      mM/L) have a higher risk of cardiovascular death. The correlation with the
      pattern and severity of their coronary atherosclerosis, especially in the new
      patients with "mild" diabetes (7.0 mM/L < or = fasting plasma glucose < 7.8
      mM/L), remains unclear. METHODS: A cohort of 466 patients undergoing coronary
      angiography but free of any previous infarction, coronary intervention and
      insulin therapy were prospectively recruited. Ninety-three had diabetes (fasting
      plasma glucose > 7.0 mM/L or hypoglycemic oral treatment). Five angiographic
      indexes were calculated to describe severity and extent of coronary
      atherosclerosis. RESULTS: Overall, patients with diabetes had more diffuse
      coronary atherosclerosis, a greater prevalence of mild, moderate and severe
      stenoses and a two-fold higher occlusion rate than patients without diabetes,
      even after adjustment for age, gender, body mass index, hypertension, lipid
      parameters, smoking, family history of cardiovascular events and ischemic
      symptoms. Patients with "mild diabetes" had a coronary atherosclerosis pattern
      more similar to patients with normal fasting plasma glucose than to patients
      formerly defined as diabetic according to the World Health Organization criteria,
      except that they had a higher prevalence of <50% stenoses. CONCLUSIONS: In
      patients with type 2 diabetes, those with 7.0 mM/L < or = fasting plasma glucose
      < 7.7 mM/L have a slightly greater prevalence of mildly severe lesions that may
      partly explain their higher cardiovascular event rate.

PMID- 11345362
TI  - Association of angiotensinogen M235T and A(-6)G gene polymorphisms with coronary
      heart disease with independence of essential hypertension: the PROCAGENE study.
      Prospective Cardiac Gene.
AB  - OBJECTIVES: We examined the relationship between the angiotensinogen (AGT) gene
      M235T polymorphism, the variant promoter of the AGT gene A(-6)G and the
      angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism
      and coronary heart disease (CHD) in native Gran Canaria Island habitants, who
      have the highest rates of CHD in Spain. BACKGROUND: Some studies subject that the
      ACE (I/D) polymorphism could be associated with CHD, while AGT (M235T) has been
      related to essential hypertension. METHODS: We studied 304 subjects with
      angiographic evidence of coronary artery disease and a clinical diagnosis of
      myocardial infarction or unstable angina and 315 age- and gender-matched
      controls. Blood was drawn and DNA extracted. Angiotensin-converting enzyme (I/D)
      gene polymorphism was analyzed by polymerase chain reaction (PCR) and AGT gene
      polymorphisms by restriction fragment length polymorphism-PCR and mutagenically
      separated PCR. RESULTS: The ACE (I/D) polymorphism showed no association with
      CHD, whereas the frequency distribution of AGT (M235T) genotypes among patients
      and controls (235T: 29.1% and 19.0%; M235T: 48.5% and 50.2%; M235: 22.4% and
      30.8%, respectively) was statistically different (p = 0.005) and not related to
      the presence of essential hypertension. Similar results were observed with the
      AGT A(-6)G polymorphism. In multiple logistic regression analysis, CHD odds ratio
      associated with 235T and M235 homozygotes were 1.7 (1.1 to 2.6) and 0.54 (0.36 to
      0.82), respectively. CONCLUSIONS: This study shows that genetic variation of the
      AGT (M235T), but not the ACE (I/D), genotypes contributes to the presence of CHD
      independently of blood pressure profile in a subset of the Spanish population
      with a high prevalence of cardiovascular disease.

PMID- 11345364
TI  - Prognostic stratification of diabetic patients by exercise echocardiography.
AB  - OBJECTIVES: The aim of this study was to assess the incremental value of exercise
      echocardiography for the risk stratification of diabetic patients. BACKGROUND:
      There are currently insufficient outcome data in diabetic patients to define the
      role of stress echocardiography as a prognostic tool. METHODS: We studied the
      prognostic value of exercise echocardiography in 563 patients with diabetes
      mellitus (mean age 64 +/- 11 years, 336 men) and known or suspected ischemic
      heart disease (IHD). RESULTS: Cardiac events occurred in 50 patients (cardiac
      death in 23 and nonfatal myocardial infarction [MI] in 27) during a median follow
      up period of three years. Event rate was lower in patients with normal as
      compared to those with abnormal exercise echocardiography at one year (0% vs.
      1.9%), three years (1.8% vs. 11.9%), and five years (7.6% vs. 23.3%),
      respectively (p = 0.0001). Patients with multivessel distribution of
      echocardiographic abnormalities had the highest event rate (2.9% at one year,
      15.2% at three years, and 32.8% at five years). In an incremental multivariate
      analysis model, exercise echocardiography increased the chi-square of the
      clinical and exercise ECG model from 29 to 44.8 (p = 0.0001). CONCLUSIONS:
      Exercise echocardiography provides incremental data for risk stratification of
      diabetic patients with known or suspected IHD. Patients with a normal exercise
      echocardiogram have a low event rate. Patients with multivessel distribution of
      exercise echocardiographic abnormalities are at the highest risk of cardiac
      events, as one-third of these patients experience cardiac death or nonfatal MI
      during the five years following exercise echocardiography.

PMID- 11345365
TI  - Independent contribution of myocardial perfusion defects to exercise capacity and
      heart rate recovery for prediction of all-cause mortality in patients with known
      or suspected coronary heart disease.
AB  - OBJECTIVES: The goal of this study was to determine the value of thallium201
      single photon emission computed tomography (SPECT) imaging for prediction of all
      cause mortality when considered along with functional capacity and heart rate
      recovery. BACKGROUND: Myocardial perfusion defects identified by thallium201
      SPECT imaging are predictive of cardiac events. Functional capacity and heart
      rate recovery are exercise measures that also have prognostic implications.
      METHODS: We followed 7,163 consecutive adults referred for symptom-limited
      exercise thallium SPECT (mean age 60 +/- 10, 25% women) for 6.7 years. Using
      information theory, we identified a probable best model relating nuclear findings
      to outcome to calculate a prognostic nuclear score. RESULTS: There were 855
      deaths. Intermediate- and high-risk prognostic nuclear scores were noted in 28%
      and 10% of patients. Compared with those with low-risk scans, patients with an
      intermediate-risk score were at increased risk for death (14% vs. 9%, hazard
      ratio: 1.67, 95% confidence interval [CI]: 1.44 to 1.95, p < 0.0001), while those
      with high-risk scores were at greater risk (24%, hazard ratio: 2.98, 95% CI: 2.49
      to 3.56, p < 0.0001). In multivariable analyses that adjusted for clinical
      characteristics, functional capacity and heart rate recovery, an intermediate
      risk nuclear score remained predictive of death (adjusted hazard ratio: 1.50, 95%
      CI: 1.28 to 1.76, p < 0.0001), as did a high-risk score (adjusted hazard ratio:
      2.76, 95% CI: 2.13 to 2.56, p < 0.0001). Impaired functional capacity and
      decreased heart rate recovery provided additional prognostic information.
      CONCLUSIONS: Myocardial perfusion defects detected by thallium SPECT imaging are
      independently predictive of long-term all-cause death, even after accounting for
      exercise capacity, heart rate recovery and other potential confounders.

PMID- 11345366
TI  - Bradykinin stimulates the release of tissue plasminogen activator in human
      coronary circulation: effects of angiotensin-converting enzyme inhibitors.
AB  - OBJECTIVES: The goal of this study was to determine: 1) whether bradykinin (BK)
      directly stimulates tissue plasminogen activator (tPA) secretion in human
      coronary circulation, and 2) whether angiotensin-converting enzyme (ACE)
      inhibition favorably alters the fibrinolytic balance regulated by BK. BACKGROUND:
      Bradykinin is a potent stimulator of tPA secretion in endothelial cells; however,
      the effect of BK on tPA release in the human coronary circulation has not been
      studied. METHODS: Fifty-six patients with atypical chest pain were randomly
      assigned to two groups: 25 patients were treated with the ACE inhibitor enalapril
      (ACE inhibitor group), and 31 were not treated with ACE inhibitors (non-ACE
      inhibitor group). Graded doses of BK (0.2, 0.6, 2.0 microg/min), acetylcholine
      (ACh) (30 microg/min) and papaverine (PA) (12 mg) were administered into the left
      coronary artery. Coronary blood flow (CBF) was evaluated by Doppler flow velocity
      measurement. Blood samples were taken from the aorta (Ao) and the coronary sinus
      (CS). RESULTS: Bradykinin induced similar increases in CBF in both groups. The
      net tPA release induced by BK was dose-dependently increased in both groups, and
      the extent of that increase in the ACE inhibitor group was greater than that in
      the non-ACE inhibitor group. Bradykinin did not alter plasminogen activator
      inhibitor-1 (PAI-1) levels in the Ao or CS in either group. Neither ACh nor PA
      altered tPA levels or PAI-1 levels in either group. CONCLUSIONS: Intracoronary
      infusion of BK stimulates tPA release without causing any change in PAI-1 levels
      in the human coronary circulation. In addition, this effect of BK is augmented by
      an ACE inhibitor.

PMID- 11345367
TI  - Twenty-two year (1975 to 1997) trends in the incidence, in-hospital and long-term
      case fatality rates from initial Q-wave and non-Q-wave myocardial infarction: a
      multi-hospital, community-wide perspective.
AB  - OBJECTIVES: The goal of this study was to examine long-term trends in the
      incidence, in-hospital and long-term mortality patterns in patients with an
      initial non-Q-wave myocardial infarction (NQWMI) as compared with those with an
      initial Q-wave myocardial infarction (QWMI). BACKGROUND: Limited data are
      available describing trends in the incidence and mortality from an initial QWMI
      and NQWMI from a multi-hospital community-wide perspective. METHODS: Our study
      was an observational study of 5,832 metropolitan Worcester, Massachusetts
      residents (1990 census = 437,000) hospitalized with validated initial acute MI in
      all greater Worcester hospitals during 11 annual periods between 1975 and 1997.
      RESULTS: The incidence of QWMI progressively decreased between 1975/78 (incidence
      rate = 171/100,000 population) and 1997 (101/100,000 population). In contrast,
      the incidence of NQWMI progressively increased between 1975/78 (62/100,000
      population) and 1997 (131/100,000 population). Hospital death rates were 19.5%
      for patients with QWMI and 12.5% for those with NQWMI. After controlling for
      various covariates, patients with QWMI remained at significantly increased risk
      for hospital mortality (adjusted odds ratio = 1.63; 95% confidence interval:
      1.35, 1.97). While the hospital mortality of QWMI has progressively declined over
      time (1975/78 = 24%; 1997 = 14%), the in-hospital mortality for NQWMI has
      remained the same (1975/78 = 12%; 1997 = 12%). These trends remained after
      adjusting for potentially confounding prognostic factors. The multivariable
      adjusted two-year mortality after hospital discharge declined over time for
      patients with QWMI and NQWMI. CONCLUSIONS: Despite impressive declines in the
      incidence, in-hospital and long-term mortality associated with QWMI, NQWMI is
      increasing in frequency and has the same in-hospital mortality now as it did 22
      years ago.

PMID- 11345368
TI  - Consequences of overutilization and underutilization of thrombolytic therapy in
      clinical practice. TRACE Study Group. TRAndolapril Cardiac Evaluation.
AB  - OBJECTIVES: The aim of this study was to evaluate the consequences, measured as
      mortality and in-hospital stroke, of the use of thrombolytic therapy among
      patients with acute myocardial infarction (AMI), who do not fulfill accepted
      criteria or who have contraindications to thrombolytic therapy (i.e.,
      overutilization) and among patients who are withheld thrombolytic treatment
      despite fulfilling indications and having no contraindications (i.e.,
      underutilization). BACKGROUND: The implementation of treatment with thrombolysis
      in clinical practice is not in accordance with the accepted criteria from
      randomized studies. The consequence has been over- and underutilization of
      thrombolytic therapy among patients with AMI in clinical practice. The outcome of
      overutilization of thrombolytic therapy has not been described previously.
      METHODS: We examined 6,676 consecutive patients admitted to the hospital with an
      AMI and recorded characteristics, in-hospital complications and long-term
      mortality. RESULTS: Overall, 41% of the patients received thrombolytic therapy.
      Thrombolytic therapy was underutilized in 14.3% and overutilized in 12.9% of the
      patients. The use of thrombolytic therapy was associated with reduced mortality
      in every subgroup examined, including patients without an accepted indication,
      with an accepted indication and in patients with prior stroke. The risk ratio of
      in-hospital stroke was not increased in connection with thrombolytic therapy, not
      even in patients with prior stroke (relative risk = 0.237, 95% confidence
      interval: 0.031 to 1.810, p = 0.17). CONCLUSIONS: With the large benefit known to
      be associated with thrombolytic therapy and the favorable result of thrombolytic
      therapy in patients with contraindications observed in this study, we conclude
      that a formal evaluation of thrombolytic therapy in wider patient categories is
      warranted.

PMID- 11345369
TI  - Overutilization and underutilization of thrombolysis in routine clinical
      practice.

PMID- 11345370
TI  - Detailed endocardial mapping accurately predicts the transmural extent of
      myocardial infarction.
AB  - OBJECTIVES: This study delineates between infarcts varying in transmurality by
      using endocardial electrophysiologic information obtained during catheter-based
      mapping. BACKGROUND: The degree of infarct transmurality extent has previously
      been linked to patient prognosis and may have significant impact on therapeutic
      strategies. Catheter-based endocardial mapping may accurately delineate between
      infarcts differing in the transmural extent of necrotic tissue. METHODS:
      Electromechanical mapping was performed in 13 dogs four weeks after left anterior
      descending coronary artery ligation, enabling three-dimensional reconstruction of
      the left ventricular chamber. A concomitant reduction in bipolar electrogram
      amplitude (BEA) and local shortening indicated the infarcted region. In addition,
      impedance, unipolar electrogram amplitude (UEA) and slew rate (SR) were
      quantified. Subsequently, the hearts were excised, stained with 2,3,5
      triphenyltetrazolium chloride and sliced transversely. The mean transmurality of
      the necrotic tissue in each slice was determined, and infarcts were divided into
      <30%, 31% to 60% and 61% to 100% transmurality subtypes to be correlated with the
      corresponding electrical data. RESULTS: From the three-dimensional
      reconstructions, a total of 263 endocardial points were entered for correlation
      with the degree of transmurality (4.6 +/- 2.4 points from each section). All four
      indices delineated infarcted tissue. However, BEA (1.9 +/- 0.7 mV, 1.4 +/- 0.7
      mV, 0.8 +/- 0.4 mV in the three groups respectively, p < 0.05 between each group)
      proved superior to SR, which could not differentiate between the second (31% to
      60%) and third (61% to 100%) transmurality subgroups, and to UEA and impedance,
      which could not differentiate between the first (<30%) and second transmurality
      subgroups. CONCLUSIONS: The degree of infarct transmurality extent can be derived
      from the electrical properties of the endocardium obtained via detailed catheter
      based mapping in this animal model.

PMID- 11345371
TI  - Continued benefit of  coronary stenting versus balloon angioplasty: five-year
      clinical follow-up of Benestent-I trial.
AB  - OBJECTIVES: This study sought to establish whether the early favorable results in
      the Benestent-I randomized trial comparing elective Palmaz-Schatz stent
      implantation with balloon angioplasty in 516 patients with stable angina pectoris
      are maintained at 5 years. BACKGROUND: The size of the required sample was based
      on a 40% reduction in clinical events in the stent group. Seven months and one
      year follow-up in this trial showed a decreased incidence of restenosis and
      clinical events in patients randomized to stent implantation. METHODS: Data at
      five years were collected by outpatient visit, via telephone and via the
      referring cardiologist. Three patients in the stent group and one in the
      percutaneous transluminal coronary angioplasty (PTCA) group were lost to follow
      up at five years. Major clinical events, anginal status and use of cardiac
      medication were recorded according to the intention to treat principle. RESULTS:
      No significant differences were found in anginal status and use of cardiac
      medication between the two groups. In the PTCA group, 27.3% of patients underwent
      target lesion revascularization (TLR) versus 17.2% of patients in the stent group
      (p = 0.008). No significant differences in mortality (5.9% vs. 3.1%),
      cerebrovascular accident (0.8% vs. 1.2%), myocardial infarction (9.4% vs. 6.3%)
      or coronary bypass surgery (11.7% vs. 9.8%) were found between the stent and PTCA
      groups, respectively. At five years, the event-free survival rate (59.8% vs.
      65.6%; p = 0.20) between the stent and PTCA groups no longer achieved statistical
      significance. CONCLUSIONS: The original 10% absolute difference in TLR in favor
      of the stent group has remained unchanged at five years, emphasizing the long
      term stability of the stented target site.

PMID- 11345372
TI  - Different clinical features of aortic intramural hematoma versus dissection
      involving the ascending aorta.
AB  - OBJECTIVES: The goal of this study was to test the hypothesis that the absence of
      direct flow communication through intimal tear in aortic intramural hematoma
      (AIH) involving the ascending aorta has different clinical impact on clinical
      course compared with typical aortic dissection (AD). BACKGROUND: Although
      emergent surgical repair has been applied for patients with proximal AIH as if it
      was typical AD, the natural history of proximal AIH is not known clearly yet.
      METHODS: Direct comparison of the clinical data of 81 patients with proximal AD
      and 24 patients with AIH was performed retrospectively. RESULTS: Patients with
      AIH were older (67 +/- 10 vs. 50 +/- 13, p = 0.001), and female gender was more
      predominant in AIH (19/24 vs. 29/81, p = 0.001). The development of mediastinal
      hemorrhage and pericardial and pleural effusion was more frequent in patients
      with AIH than it was in patients with AD. Although medical treatment was more
      frequently selected in the AIH group (75% vs. 15%, p = 0.001) due to old age and
      other associated medical diseases, the mortality rate with medical treatment was
      much lower in patients with AIH than it was in patients with AD (6% vs. 58%, p =
      0.003). In follow-up imaging studies of 13 patients who survived AIH without
      surgical repair, seven patients showed complete resolution. Typical AD developed
      in three patients, and the other three patients showed focal AD only in the
      descending aorta. The two-year survival rate did not show significant difference
      (84% +/- 6% in AIH vs. 76% +/- 17% in AD, p = 0.47). CONCLUSIONS: Absence of
      continuous flow communication can explain a more favorable clinical course of AIH
      than for AD, and medical treatment with frequent imaging follow-up and timed
      elective surgery in cases with complications can be a rational option for
      patients with proximal AIH.

PMID- 11345373
TI  - Aortic intramural hematoma: from observation to therapeutic strategies.

PMID- 11345374
TI  - Specificity of Doppler echocardiography for the assessment of changes in valvular
      regurgitation: comparison of side-by-side versus serial interpretation.
AB  - OBJECTIVES: We sought to determine the specificity of two different methods for
      assessing change in aortic (AR), mitral (MR) and tricuspid (TR) valvular
      regurgitation. BACKGROUND: Echocardiographic imaging with Doppler is the standard
      noninvasive diagnostic tool for assessing valvular structure and function. Change
      can be assessed using either independent evaluations (serial) or using a side-by
      side comparison. METHODS: Subjects were from the placebo arm of a randomized,
      double-blind, clinical trial. Three echocardiograms over 10 months were
      performed. An initial and three-month echocardiogram were read as independent
      groups, blinded to all parameters except sequence. The initial and 10-month
      echocardiograms were read side-by-side, blinded to all parameters including
      sequence. RESULTS: Two hundred nineteen predominantly healthy, obese, white,
      middle-aged women had initial and three-month echocardiograms (acquisition
      interval 105 +/- 28 days) evaluated by the serial method (mean 167 +/- 61 days
      between interpretations). The same subjects had the initial and 10-month studies
      (acquisition interval 303 +/- 27 days) compared side-by-side. The specificity of
      the serial versus side-by-side method for determining change in MR grade was
      55.8% versus 93.2% (p < 0.001); TR: 63.8% versus 97.6% (p < 0.001) and AR: 93.7%
      versus 97.6 (p = 0.08). Notably, most of the change occurred in a range (none
      versus physiologic/mild) that has limited clinical significance. Furthermore, the
      percentage of echocardiograms interpreted as nonevaluable was lower with the side
      by-side method for MR (5.0% vs. 16.0%, p = 0.06), TR (4.6% vs. 15.5%, p < 0.001)
      and AR (4.1% vs. 12.3%, p = 0.002). CONCLUSIONS: The side-by-side method of
      assessing change in valvular regurgitation appears to be the more reliable method
      with a higher specificity and minimal data loss.

PMID- 11345375
TI  - Long-term follow-up of atrial contraction after the maze procedure in patients
      with mitral valve disease.
AB  - OBJECTIVES: We sought to determine the effectiveness of the maze procedure for
      maintaining sinus rhythm and atrial contraction for a long period in patients
      with mitral valve disease. BACKGROUND: Although the maze procedure for atrial
      fibrillation (AF) has been effective in restoring sinus rhythm in patients with
      mitral valve disease, the long-term results of this procedure have not been
      determined. METHODS: We echocardiographically studied 94 consecutive patients
      with mitral valve disease before, as well as early (3.1 +/- 3.3 months) and late
      (2.2 +/- 0.9 years) after, the maze procedure. Peak velocity and the time
      velocity integral of the left ventricular (LV) diastolic filling wave during
      atrial contraction (A wave), as well as the atrial filling fraction (calculated
      as the ratio of the time-velocity integral of the A wave to total diastolic
      filling), were obtained from transmitral flow recordings. Peak A wave velocity >
      or =10 cm/s was considered to indicate echocardiographic evidence of effective
      atrial contraction. RESULTS: Regular rhythm with P waves was restored in 70
      patients (74%) in the early stage and in 59 patients (63%, p = 0.09) in the late
      stage after the maze procedure. Forty-seven patients (50%) in the early stage and
      36 patients (38%, p = 0.14) in the late stage showed effective atrial contraction
      by Doppler echocardiography. Left atrial (LA) and LV end-diastolic diameters
      significantly decreased after the procedure (from 59 +/- 13 to 48 +/- 7 mm, p <
      0.01; and from 54 +/- 9 to 47 +/- 5 mm, p < 0.01, respectively) and did not show
      significant changes during the follow-up period. Once atrial contraction was
      resumed, its degree did not change between the early and late stages after the
      maze procedure (17 +/- 6% vs. 17 +/- 6% for atrial filling fraction).
      CONCLUSIONS: Sinus rhythm and atrial contraction recovered early after the maze
      procedure in most patients and were maintained for more than two years. Once
      active atrial contraction was resumed, the degree of contraction did not change
      thereafter. These results demonstrate that the maze procedure is effective for a
      long period in patients with mitral valve disease.

PMID- 11345376
TI  - Assessment of noninvasive markers in identifying patients at risk in the Brugada
      syndrome: insight into risk stratification.
AB  - OBJECTIVES: The aim of this study was to compare the use of various noninvasive
      markers for detecting risk of life-threatening arrhythmic events in patients with
      Brugada syndrome. BACKGROUND: The role of conduction disturbance in
      arrhythmogenesis of the syndrome is controversial, whereas it is well established
      that repolarization abnormalities are responsible for arrhythmias. The value of
      noninvasive markers reflecting conduction or repolarization abnormalities in
      identifying patients at risk for significant arrhythmias has not been shown.
      METHODS: We assessed late potentials (LP) using signal-averaged
      electrocardiography (ECG), microvolt T-wave alternans (TWA), and corrected QT
      interval dispersion (QTD) in 44 consecutive patients who had ECGs showing a
      pattern of right bundle branch block and ST-segment elevation in leads V1 to V3
      but structurally normal hearts. The patients were compared with 30 normal
      individuals. RESULTS: Eleven patients were excluded from data analysis because of
      an absence of ECG manifestations of Brugada syndrome at the time of the tests. A
      history of life-threatening events defined as syncope and aborted sudden death
      was present in 19 of 33 patients (58%); in 15 of the 19 patients, stimulation
      induced ventricular fibrillation or polymorphic ventricular tachycardia. The LP
      were present in 24 of 33 patients (73%); TWA were present in 5 of 31 patients
      (16%); and a QTD >50 ms was present in 9 of 33 patients (27%). The incidence of
      LP in Brugada patients was significantly (p < 0.0001) higher than in the
      controls, whereas incidences of TWA and QTD were not significantly different.
      Multivariate logistic regression analysis revealed that the presence of LP had
      the most significant correlation to the occurrence of life-threatening events (p
      = 0.006). CONCLUSIONS: Late potentials are a noninvasive risk stratifier in
      patients with Brugada syndrome. These results may support the idea that
      conduction disturbance per se is arrhythmogenic.

PMID- 11345377
TI  - Clinical diagnosis and risk stratification in patients with Brugada syndrome.

PMID- 11345378
TI  - Response to flecainide infusion predicts long-term success of hybrid
      pharmacologic and ablation therapy in patients with atrial fibrillation.
AB  - OBJECTIVES: We tested the hypothesis that the response to flecainide infusion can
      identify patients with atrial fibrillation (AF) in whom the hybrid pharmacologic
      and ablation therapy reduces the recurrences of AF. BACKGROUND: Infusion of class
      IC anti-arrhythmic drugs may promote transformation of AF into atrial flutter.
      Catheter ablation of atrial flutter has been demonstrated to be highly effective
      in preventing recurrences of atrial flutter. METHODS: Seventy-one consecutive
      patients with paroxysmal or chronic AF, in whom flecainide infusion (2 mg/kg body
      weight, intravenously) determined the transformation of AF into common atrial
      flutter (positive response), were randomized to receive one of the following
      treatments: oral pharmacologic treatment with flecainide (group A, n = 23); the
      hybrid treatment (catheter ablation of the inferior vena cava-tricuspid annulus
      isthmus, plus oral flecainide) (group B, n = 24); or catheter ablation of the
      isthmus only (group C, n = 24). Thirty-seven patients with a negative response to
      flecainide, who chose to be submitted to the hybrid treatment, were selected as
      the control group (group D). RESULTS: During a mean follow-up period of 24 +/-
      7.2 months, the recurrences of AF and atrial flutter in group B (42%) were
      significantly lower than those in group A (78%, p < 0.001), group C (92%, p <
      0.001) and group D (92%, p < 0.001). CONCLUSIONS: The creation of a complete bi
      directional conduction block at the inferior vena cava-tricuspid annulus isthmus,
      plus flecainide administration, reduces the recurrences of both AF and atrial
      flutter in patients with class IC atrial flutter. Moreover, the early response to
      flecainide is safe and reliable in identifying patients who may benefit from this
      therapy.

PMID- 11345379
TI  - Optimized mapping of slow pathway ablation guided by subthreshold stimulation: a
      randomized prospective study in patients with recurrent atrioventricular nodal re
      entrant tachycardia.
AB  - OBJECTIVES: This randomized prospective study sought to assess the value of slow
      pathway (SP) mapping and ablation guided by subthreshold stimulation (STS) in
      comparison with a strategy based on conventional criteria. BACKGROUND: Previous
      studies have demonstrated that STS can be used as a highly specific and sensitive
      marker for successful SP ablation in the setting of atrioventricular nodal re
      entrant tachycardia (AVNRT). Nonetheless, thus far this mapping strategy has not
      been investigated in contrast with the conventional approach. METHODS: One
      hundred patients with sustained AVNRT were included. Fifty patients (group A)
      were randomly assigned to endocardial mapping and SP ablation using currently
      established criteria. In the other 50 patients (group B), SP ablation was guided
      by STS mapping. In group B patients, only radiofrequency current (RFC) was
      applied if additionally constant current STS (up to 5 mA) during AVNRT
      interrupted the tachycardia due to selective block within the SP. RESULTS:
      Termination of AVNRT without apparent capture was observed during STS in 47 of 50
      group B patients (94%). In all cases, this effect was indicative for successful
      subsequent SP ablation. The mean number of RFC pulses required for successful SP
      ablation was significantly lower in patients assigned to the STS-guided strategy
      (1.6 +/- 1.3 vs. 3.9 +/- 3.4; p = 0.0003). Similarly, the mean procedure duration
      was shorter in the STS group (156.9 +/- 33.5 vs. 173.2 +/- 49.7 min; p = 0.0221);
      the fluoroscopy time was comparable between both groups (14.1 +/- 8.7 vs. 16.9 +/
      10.6 min; p = 0.1278). CONCLUSIONS: Subthreshold stimulation is an effective
      method for detection of target sites for selective SP ablation. This technique
      helps to minimize the number of RFC pulses without prolongation of the overall
      procedure and fluoroscopy time required for SP ablation.

PMID- 11345380
TI  - Prolonged fractionation of paced right atrial electrograms in patients with
      atrial flutter and fibrillation.
AB  - OBJECTIVES: This study investigated the extent of fractionation of paced right
      atrial electrograms in patients with and without paroxysmal atrial flutter (AFL)
      or atrial fibrillation (AF). BACKGROUND: Slow conduction through nonuniform
      anisotropic atrial muscles, represented by fractionated electrograms, may favor
      the generation of atrial tachyarrhythmias. METHODS: This study included 10
      control patients (Group 1), 8 patients with documented paroxysmal AFL (Group 2)
      and 10 patients with documented paroxysmal AF (Group 3). Five electrode catheters
      were placed in the different sites of the right atrium and one catheter was
      positioned at the coronary sinus ostium. Atrial pacing from one site was done by
      a constant drive train with an extrastimulus inserted every fourth beat while
      recording at the other five sites was performed. The delay of each fractionated
      potential in the high-pass filtered atrial electrogram in response to
      extrastimulation was determined and used to construct conduction curves of delay
      versus the S1S2 interval. RESULTS: The mean increase in electrogram duration
      between a coupling interval of 350 ms and 10 ms above atrial refractoriness was
      significantly greater in Groups 2 and 3 compared with that in Group 1 (8.5 +/-
      2.5 vs. 11.0 +/- 2.7 vs. 5.9 +/- 2.3 ms, respectively, p < 0.001). The mean S1S2
      interval at which delay increased suddenly was also longer in Groups 2 and 3
      compared with Group 1 (326 +/- 9 vs. 343 +/- 12 vs. 307 +/- 17 ms, respectively,
      p < 0.001). CONCLUSIONS: Increased delays in the individual potential of the
      fractionated atrial electrograms may be related to the development of AFL and AF.

PMID- 11345381
TI  - Electrophysiologic characteristics in initiation of paroxysmal atrial
      fibrillation from a focal area.
AB  - OBJECTIVES: We investigated the electrophysiologic characteristics in the
      initiation of paroxysmal atrial fibrillation (PAF) from a focal area. BACKGROUND:
      The electrophysiologic characteristics in the initiation of PAF are still not
      clear. METHODS: The study group consisted of 77 patients (M/F = 65/12, age 66 +/-
      12 years) with frequent episodes of PAF; we analyzed: 1) 15 cycle lengths of
      electrical activity before the onset of atrial fibrillation (AF); 2) coupling
      interval (CI) of the first ectopic beat just before the initiation of AF; and 3)
      the prematurity of an ectopic beat (prematurity index [PI] = CI/mean of preceding
      15 cycle lengths). RESULTS: A total of 111 episodes of sustained AF were
      identified. Two patterns of AF initiation were observed: group I (59/111, 53%)
      included the episodes preceded by cycle length oscillation, and group II (52/111,
      47%) included the episodes initiated by a single ectopic beat with preceding
      cycle length relatively constant. The PI of group I episodes was significantly
      greater than that of group II (0.41 +/- 0.12 vs. 0.34 +/- 0.10, p < 0.01). The CI
      (267 +/- 54 ms vs. 217 +/- 55 ms, p < 0.05), AF1 (194 +/- 36 ms vs. 153 +/- 37
      ms, p < 0.05) and PI (0.49 +/- 0.13 vs. 0.37 +/- 0.11, p < 0.01) of the AF
      episodes from the superior vena cava (SVC) were significantly longer and greater
      than those of AF episodes from pulmonary veins (PVs). CONCLUSIONS: In patients
      with PAF originating from PVs or the SVC, two major initiating patterns were
      found. Moreover, the electrophysiologic characteristics in the initiation of AF
      originating from the SVC were also different from those of AF initiating from the
      PVs.

PMID- 11345382
TI  - Multi atrial maco-re-entry circuits in adults with repaired congenital heart
      disease: entrainment mapping combined with three-dimensional electroanatomic
      mapping.
AB  - OBJECTIVES: We sought to characterize re-entry circuits causing intra-atrial re
      entrant tachycardias (IARTs) late after the repair of congenital heart disease
      (CHD) and to define an approach for mapping and ablation, combining anatomy,
      activation sequence data and entrainment mapping. BACKGROUND: The development of
      IARTs after repair of CHD is difficult to manage and ablate due to complex
      anatomy, variable re-entry circuit locations and the frequent co-existence of
      multiple circuits. METHODS: Forty-seven re-entry circuits were mapped in 20
      patients with recurrent IARTs refractory to medical therapy. In the first group
      (n = 7), ablation was guided by entrainment mapping. In the second group (n =
      13), entrainment mapping was combined with a three-dimensional electroanatomic
      mapping system to precisely localize the scar-related boundaries of re-entry
      circuits and to reconstruct the activation pattern. RESULTS: Three types of right
      atrial macro-re-entrant circuits were identified: those related to a lateral
      right atriotomy scar (19 IARTs), the Eustachian isthmus (18 IARTs) or an atrial
      septal patch (8 IARTs). Two IARTs originated in the left atrium. Radiofrequency
      (RF) lesions were applied to transect critical isthmuses in the right atrium. In
      three patients, the combined mapping approach identified a narrow isthmuses in
      the lateral atrium, where the first RF lesion interrupted the circuit; the
      remaining circuits were interrupted by a series of RF lesions across a broader
      path. Overall, 38 (81%) of 47 IARTs were successfully ablated. During follow-up
      ranging from 3 to 46 months, 16 (80%) of 20 patients remained free of recurrence.
      Success was similar in the first 7 (group 1) and last 13 patients (group 2), but
      fluoroscopy time decreased from 60 +/- 30 to 24 +/- 9 min/procedure, probably
      related to the increasing experience and ability to monitor catheter position non
      fluoroscopically. CONCLUSIONS: Entrainment mapping combined with three
      dimensional electroanatomic mapping allows delineation of complex re-entry
      circuits and critical isthmuses as targets for ablation. Radiofrequency catheter
      ablation is a reasonable option for treatment of IARTs related to repair of CHD.

PMID- 11345383
TI  - Relationship of current and past smoking to mortality and morbidity in patients
      with left ventricular dysfunction.
AB  - OBJECTIVES: The aim of this study was to evaluate the impact of smoking in
      patients with left ventricular dysfunction. BACKGROUND: The impact of smoking in
      patients with left ventricular dysfunction has not been well-studied. METHODS: We
      compared the incidence of death, hospitalization due to heart failure and
      myocardial infarction (MI) in current smokers to ex-smokers of < or =2 years and
      ex-smokers of >2 years duration to never-smokers among participants of the Study
      Of Left Ventricular Dysfunction (SOLVD) Prevention and Intervention trials.
      Participants all had left ventricular ejection fraction (LVEF) <35% and follow-up
      was over a mean of 41 months. RESULTS: Complete smoking status and outcome data
      were available in 6,704 subjects. There were 1,562 current smokers, 1,317 ex
      smokers of < or =2 years, 2,354 ex-smokers of >2 years and 1,471 never-smokers.
      After adjusting for baseline differences of age, LVEF, race and etiology of heart
      failure, current smoking was associated with a significantly increased all-cause
      mortality (relative risk [RR]: 1.41, 95% confidence interval [CI]: 1.25 to 1.58,
      p < 0.001) compared with ex-smokers and never-smokers. The incidence of death or
      recurrent congestive heart failure requiring hospitalization or MI was
      significantly greater (RR: 1.39, 95% CI: 1.26 to 1.52, p < 0.001) in current
      smokers compared with ex-smokers and never-smokers. There were no significant
      differences in the number of deaths or hospitalizations due to heart failure
      between ex-smokers and never-smokers. This effect was consistent across both the
      SOLVD Prevention and Treatment trials. CONCLUSIONS: Current smoking is a powerful
      independent predictor of morbidity (recurrent heart failure and MI) and mortality
      in patients with left ventricular dysfunction. Quitting smoking appears to have a
      substantial and early effect (within two years) on decreasing morbidity and
      mortality in patients with left ventricular dysfunction, which is at least as
      large as proven drug treatments recommended in patients with left ventricular
      dysfunction.

PMID- 11345384
TI  - Smoking cessation in heart failure: it is never too late.

PMID- 11345385
TI  - Dobutamine echocardiographic study in patients with nonischemic dilated
      cardiomyopathy and prognostically borderline values of peak exercise oxygen
      consumption: 18-month follow-up study.
AB  - OBJECTIVES: We sought to study the prognostic value of dobutamine
      echocardiography in patients with nonischemic dilated cardiomyopathy (DCM) and
      prognostically borderline values of peak oxygen consumption (VO2max) during
      exercise. BACKGROUND: Changes in echocardiographic variables assessed by
      dobutamine echocardiography can be used to evaluate the functional status of
      patients with chronic heart failure (CHF) and DCM. METHODS: In 27 consecutive
      patients (mean age 55 +/- 15 years) with VO2max values between 10 and 14 ml/kg
      body weight per min, a low infusion rate (10 microg/kg per min) dobutamine
      echocardiographic test was performed. The induced changes in echocardiographic
      variables were measured, and an 18-month follow-up study was done. RESULTS: At
      the end of the protocol, 9 patients (group I) had died from cardiac reasons,
      whereas the remaining 18 patients (group II) survived. After dobutamine infusion,
      the left ventricular end-systolic diameter (LVESD) was smaller in group II (6.22
      +/- 0.94 cm) than in group I (6.99 +/- 0.76 cm; p < 0.05), whereas end-systolic
      wall stress (ESWS) was higher in group I (1030.66 +/- 193.98 g/cm2) than in group
      II (691.57 +/- 297.06 g/cm2; p < 0.05). The changes in LVESD and ESWS were
      greater in group I (0.75 +/- 0.36 cm and 463.11 +/- 159.87 g/cm2, respectively)
      than in group II (-0.04 +/- 0.36 cm and 83.16 +/- 291.74 g/cm2, respectively; p <
      0.01 for both). CONCLUSIONS: In the "gray" zone of VO2max, dobutamine
      echocardiography seems to be a valuable prognostic indicator in patients with CHF
      and DCM.

PMID- 11345386
TI  - Influence of carvedilol on hospitalizations in heart failure: incidence, resource
      utilization and costs. U.S. Carvedilol Heart Failure Study Group.
AB  - BACKGROUND: Carvedilol reduces disease progression in heart failure, but to our
      knowledge, its effects on hospitalizations and costs have not been evaluated.
      OBJECTIVES: We examined the effects on hospitalization frequency and costs in the
      U.S. Carvedilol Heart Failure Trials Program. This program consisted of four
      concurrent, multicenter, double-blind, placebo-controlled studies involving 1,094
      patients with New York Heart Association class II to IV heart failure, which
      treated patients with placebo or carvedilol for up to 15 months (median, 6.5
      months). METHODS: Detailed resource utilization data were collected for all
      hospitalizations occurring between randomization and the end of follow-up. In
      patient care costs were estimated based on observed levels of resource use.
      RESULTS: Compared with placebo, carvedilol reduced the risk of hospitalization
      for any reason by 29% (p = 0.009), cardiovascular hospitalizations by 28% (p =
      0.034) and heart failure hospitalizations by 38% (p = 0.041). Carvedilol also
      decreased the mean number of hospitalizations per patient (for cardiovascular
      reasons 30% [p = 0.02], for heart failure 53% [p = 0.03]). Among hospitalized
      patients, carvedilol reduced severity of illness during hospital admission, as
      reflected by shorter length of stay and less frequent use of intensive care. For
      heart failure hospital admissions, carvedilol decreased mean length of stay by
      37% (p = 0.03) and mean number of intensive care unit/coronary care unit days by
      83% (p = 0.001), with similar effects on cardiovascular admissions. As a result,
      estimated inpatient care costs with carvedilol were 57% lower for cardiovascular
      admissions (p = 0.016) and 81% lower for heart failure admissions (p = 0.022).
      CONCLUSIONS: Carvedilol added to angiotensin-converting enzyme inhibition reduces
      hospitalization risk as well as severity of illness and resource utilization
      during admission in patients with chronic heart failure.

PMID- 11345387
TI  - The effect of short-term prophylactic methylprednisolone on the incidence and
      severity of postpericardiotomy syndrome in children undergoing cardiac surgery
      with cardiopulmonary bypass.
AB  - OBJECTIVE: The aim of this study was to determine the effect of prophylactic
      immune suppression on the incidence and severity ofpostpericardiotomy syndrome
      (PPS) in children after cardiac surgery with cardiopulmonary bypass (CPB).
      BACKGROUND: Prophylactic suppression of the inflammatory response has an unknown
      effect on the incidence and severity of PPS in children undergoing surgery with
      CPB. METHODS: This randomized double-blind placebo controlled trial included two
      study groups. Group A received pre-CPB intravenous methylprednisolone (1 mg/kg)
      plus four additional intravenous doses over 24 h, and Group B received
      intravenous saline placebo at identical intervals. Data included patient
      demographics, cardiac diagnosis/operation, CPB time, incidence and severity of
      PPS. Noncomplicated PPS--temperature >100.5 degrees F, pericardial friction rub,
      patient irritability, small pericardial +/- pleural effusion. Complicated PPS-
      noncomplicated PPS plus hospital readmission +/- pericardiocentesis or
      thoracentesis. RESULTS: We randomized 266 children: 20 exclusions (6
      perioperative deaths, 14 reasons unrelated to treatment) leaving Group A (n =
      126) and Group B (n = 120). There were no significant group differences in
      gender, cardiac diagnosis or CPB time. Group mean age differed (p = 0.05) and was
      treated as a covariate with no substantive outcome effect. In total, 39/246
      children (16%) developed PPS (noncomplicated: n = 30, complicated: n = 9). There
      was no inter-group difference in overall PPS incidence (p = 0.73). However, Group
      A had a marginally significant increase in complicated PPS (p = 0.05).
      CONCLUSIONS: Intravenous methylprednisolone at a standard anti-inflammatory dose
      administered pre-CPB and early post-CPB neither prevents nor attenuates PPS in
      children. Short-term pre-CPB and post-CPB methylprednisolone treatment may
      complicate PPS.

PMID- 11345388
TI  - Minimally invasive or interventional repair of atrial septal defects in children:
      experience in 171 cases and comparison with conventional strategies.
AB  - OBJECTIVES: The goal of this study was to evaluate percutaneous interventional
      and minimally invasive surgical closure of secundum atrial septal defect (ASD) in
      children. BACKGROUND: Concern has surrounded abandoning conventional midline
      sternotomy in favor of the less invasive approaches pursuing a better cosmetic
      result and a more rational resource utilization. METHODS: A retrospective
      analysis was performed on the patients treated from June 1996 to December 1998.
      RESULTS: One hundred seventy-one children (median age 5.8 years, median weight
      22.1 kg) underwent 52 device implants, 72 minimally invasive surgical operations
      and 50 conventional sternotomy operations. There were no deaths and no residual
      left to right shunt in any of the groups. The overall complication rate causing
      delayed discharge was 12.6% for minimally invasive surgery, 12.0% for midline
      sternotomy and 3.8% for transcatheter device closure (p < 0.01). The mean
      hospital stay was 2.8 +/- 1.0 days, 6.5 +/- 2.1 days and 2.1 +/- 0.5 days (p <
      0.01); the skin-to-skin time was 196 +/- 43 min, 163 +/- 46 min and 118 +/- 58
      min, respectively (p < 0.001). Extracorporeal circulation time was 49.9 +/- 10.1
      min in the minithoracotomy group versus 37.2 +/- 13.8 min in the sternotomy group
      (p < 0.01) but without differences in aortic cross-clamping time. Sternotomy was
      the most expensive procedure (15,000 EUR +/- 1,050 EUR vs. 12,250 EUR +/- 472 EUR
      for minithoracotomy and 13,000 EUR +/- 300 EUR for percutaneous devices).
      CONCLUSIONS: While equally effective compared with sternotomy, the cosmetic and
      financial appeal of the percutaneous and minimally invasive approaches must be
      weighed against their greater exposure to technical pitfalls. Adequate training
      is needed if a strategy of surgical or percutaneous minimally invasive closure of
      ASD in children is planned in place of conventional surgery.

PMID- 11345389
TI  - Therapeutic effects of FTY720, a new immunosuppressive agent, in a murine model
      of acute viral myocarditis.
AB  - OBJECTIVES: This study examines the efficacy of FTY720 (FTY), a new
      immunosuppressor, in the treatment of acute viral myocarditis in a murine model.
      BACKGROUND: Immunosuppressive agents have no proven therapeutic efficacy in
      experimental or clinical myocarditis. METHODS: Encephalomyocarditis virus was
      inoculated i.p. in DBA/2 mice on day 0. Postinoculation treatment consisted of
      FTY 10 mg/kg/day p.o. (FTY group), or cyclosporine A (CsA) 40 mg/kg/day p.o. (CsA
      group) or distilled water p.o. only (control group). Survival until day 14, as
      well as cardiac histopathology, virus concentrations, cytokines (interleukin [IL]
      2, IL-12, interferon [IFN]-gamma and tumor necrosis factor [TNF]-alpha) and
      nitric oxide (NO) on day 5 were examined. RESULTS: In the control and CsA groups,
      all mice died within 10 and 7 days, respectively. However, in the FTY group, 27%
      of the animals survived up to day 14. Compared with the control group, 1)
      histological scores were significantly lower in the FTY group but unchanged in
      the CsA group; 2) virus concentration was significantly higher in the CsA group
      but not in the FTY group; 3) expressions of IL-2, IL-12 and IFN-gamma in the
      heart were suppressed in both the FTY and CsA groups, though suppression was
      weaker in the FTY group; 4) TNF-alpha and NO were significantly increased in the
      CsA group but not in the FTY group. CONCLUSIONS: FTY720 had a significant
      therapeutic effect in acute experimental myocarditis without inducing excessive
      virus replication. This report is the first to describe a beneficial effect by an
      immunosuppressive agent in the treatment of acute viral myocarditis.

PMID- 11345390
TI  - Angerlike behavioral state potentiates myocardial ischemia-induced T-wave
      alternans in canines.
AB  - OBJECTIVES: The main goal of this study was to determine whether induction of an
      angerlike state can result in significant levels of T-wave alternans, a marker of
      electrical instability, in the normal and ischemic heart. BACKGROUND: Outbursts
      of anger have been implicated in the occurrence of myocardial infarction and
      sudden cardiac death, but the pathophysiologic mechanisms remain unknown.
      METHODS: A standardized behavioral challenge of eliciting an angerlike state was
      conducted before and during a 3-min period of coronary artery occlusion in six
      canines. RESULTS: Precordial T-wave alternans increased from 0.04 +/- 0.02 at
      baseline to 1.40 +/- 0.32 mV X ms (p < 0.05) during the angerlike response. When
      the angerlike state and myocardial ischemia were superimposed, the augmentation
      in T-wave alternans magnitude (to 3.27 +/- 0.61 mV X ms, p < 0.05) exceeded their
      additive effects, increasing by 130% over the angerlike state alone (p < 0.05)
      and by 390% over occlusion alone (p < 0.05). Adrenergic influences were reduced
      by the beta1-adrenergic receptor blocking agent metoprolol (1.5 mg/kg,
      intravenous), which diminished T-wave alternans magnitude (p < 0.0004 for all)
      during the angerlike response (from 1.40 +/- 0.32 to 0.80 +/- 0.17 mV x ms) and
      during the combined intervention (from 3.27 +/- 0.61 to 1.23 +/- 0.13 mV X ms).
      In five additional normal anesthetized canines, atrial pacing at 180 beats/min
      did not increase T-wave alternans magnitude monitored from lead II
      electrocardiogram. CONCLUSIONS: Provocation of an angerlike state results in T
      wave alternans in the normal heart and potentiates the magnitude of ischemia
      induced T-wave alternans. Elevation in heart rate during arousal does not appear
      to be the main factor in the development of alternans in the normal heart but may
      be an important component during myocardial ischemia. Enhanced adrenergic
      activity appears to mediate the effects in both the normal and ischemic hearts. T
      wave alternans may constitute a useful electrophysiologic measure for clinical
      use in conjunction with behavioral stress testing or ambulatory monitoring.

PMID- 11345391
TI  - Transendocardial delivery of autologous bone marrow enhances collateral perfusion
      and regional function in pigs with chronic experimental myocardial ischemia.
AB  - OBJECTIVES: We tested the hypothesis that intramyocardial injection of autologous
      bone marrow (ABM) promotes collateral development in ischemic porcine myocardium.
      We also defined, in vitro, whether bone marrow (BM) cells secrete vascular
      endothelial growth factor (VEGF) and macrophage chemoattractant protein-1 (MCP
      1). BACKGROUND: The natural processes leading to collateral development are
      extremely complex, requiring multiple growth factors interacting in concert and
      in sequence. Because optimal angiogenesis may, therefore, require multiple
      angiogenic factors, we thought that injection of BM, which contains cells that
      secrete numerous angiogenic factors, might provide optimal therapeutic
      angiogenesis. METHODS: Bone marrow was cultured four weeks in vitro. Conditioned
      medium was assayed for VEGF and MCP-1 and was added to cultured pig aortic
      endothelial cells (PAEC) to assess proliferation. Four weeks after left
      circumflex ameroid implantation, freshly aspirated ABM (n = 7) or heparinized
      saline (n = 7) was injected transendocardially into the ischemic zone (0.2
      ml/injection at 12 sites). Echocardiography to assess myocardial thickening and
      microspheres to assess perfusion were performed at rest and during stress.
      RESULTS: Vascular endothelial growth factor and MCP-1 concentrations increased in
      a time-related manner. The conditioned medium enhanced, in a dose-related manner,
      PAEC proliferation. Collateral flow (ischemic/normal zone X 100) improved in ABM
      treated pigs (ABM: 98 +/- 14 vs. 83 +/- 12 at rest, p = 0.001; 89 +/- 18 vs. 78
      +/- 12 during adenosine, p = 0.025; controls: 92 +/- 10 vs. 89 +/- 9 at rest, p =
      0.49; 78 +/- 11 vs. 77 +/- 5 during adenosine, p = 0.75). Similarly,
      contractility increased in ABM-treated pigs (ABM: 83 +/- 21 vs. 60 +/- 32 at
      rest, p = 0.04; 91 +/- 44 vs. 36 +/- 43 during pacing, p = 0.056; controls: 69 +/
      48 vs. 64 +/- 46 at rest, p = 0.74; 65 +/- 56 vs. 37 +/- 56 during pacing, p =
      0.23). CONCLUSIONS: Bone marrow cells secrete angiogenic factors that induce
      endothelial cell proliferation and, when injected transendocardially, augment
      collateral perfusion and myocardial function in ischemic myocardium.

PMID- 11345392
TI  - Ablation of atrial fibrillation in the rapid pacing canine model using a multi
      electrode loop catheter.
AB  - OBJECTIVES: This investigation details our experience using a loop catheter to
      ablate atrial fibrillation (AF) in dogs. BACKGROUND: Atrial fibrillation is the
      most common arrhythmia and has significant morbidity. Maintenance of normal sinus
      rhythm (NSR) after conversion in many patients is still a challenge. METHODS: A
      multi-electrode loop catheter was used to create linear atrial lesions to ablate
      AF in a rapid atrial pacing model in 29 dogs. Rhythm status was assessed over a
      six-month recovery period, after which tissue analysis was performed. RESULTS:
      Acute conversion to NSR or atrial tachycardia (AT) was achieved in 90% of cases.
      Six of 26 conversions occurred after only left atrial (LA) lesions, and two after
      just right atrial lesions. Sixteen (62%) of 26 lesions that resulted in AF
      conversion were in the LA, and 11 of these 16 conversions occurred during a
      lesion connecting the mitral ring to the pulmonary veins. Acute conversion rate
      was similar with ring and coil electrodes, but AT was more frequent with coil
      electrodes (63% vs. 31%). At six months 80% of dogs were in NSR, 14% were in AT,
      and 7% remained in AF. There was an average reduction in P-wave amplitude of 64
      +/- 26% after power application. Tissue analysis revealed transmural contiguous
      lesions when final outcome was NSR, and nontransmural/noncontiguous lesions where
      AF persisted. CONCLUSIONS: Multi-electrode loop catheters can create contiguous
      transmural lesions in either atrium to safely and effectively ablate AF and
      provide a stable long-term rhythm outcome in this dog model. The left atrium
      appears to be the dominant chamber that sustains AF. Atrial tachycardia is a
      frequent acute outcome with coil electrodes.

PMID- 11345393
TI  - Early autonomic and repolarization abnormalities contribute to lethal arrhythmias
      in chronic ischemic heart failure: characteristics of a novel heart failure model
      in dogs with postmyocardial infarction left ventricular dysfunction.
AB  - OBJECTIVES: Using a model of arrhythmias associated with ischemic left
      ventricular (LV) dysfunction, this study investigated autonomic and
      electrophysiologic mechanisms associated with sudden cardiac death (SCD) in
      chronic heart failure (HF). BACKGROUND: Left ventricular dysfunction from
      ischemic heart disease is associated with many instances of SCD.
      Electrophysiologic and autonomic derangements occur in HF, but their contribution
      to SCD risk is poorly understood. METHODS: Sudden death risk was assessed in 15
      dogs with a healed anterior myocardial infarction (MI) during submaximal exercise
      and brief acute circumflex ischemia. Left ventricular dysfunction was then
      induced by repetitive circumflex microembolization until LV ejection fraction
      reached 35%. Before embolization, six dogs were susceptible to SCD, and nine were
      resistant. RESULTS: Baroreflex sensitivity was lower in susceptible dogs (10
      ms/mm Hg +/- 4 ms/mm Hg vs. 20 ms/mm Hg +/- 11 ms/mm Hg, p = 0.04). QT intervals
      from susceptible dogs were longer after MI (246 ms +/- 26 ms susceptible vs. 231
      ms +/- 20 ms resistant, p < 0.001) and prolonged within eight weeks after LV
      dysfunction was established (from 246 ms +/- 26 ms to 274 ms +/- 56 ms, +11%, p <
      0.01). Heart rate in susceptible dogs increased during transient ischemia (+20%)
      and with progressive LV dysfunction (102 beats/min +/- 28 beats/min baseline to
      154 beats/min +/- 7 beats/min LV dysfunction, p = 0.003). All susceptible dogs
      had spontaneous sustained ventricular tachycardia culminating in SCD. In
      contrast, QT intervals in resistant dogs prolonged after 24 +/- 6 weeks (from 231
      ms +/- 20 ms to 238 ms +/- 15 ms, p < 0.05), and heart rates were unchanged. Only
      one resistant dog died suddenly with LV dysfunction. CONCLUSIONS: Depressed vagal
      and elevated sympathetic control of heart rate coupled with abnormal
      repolarization are associated with high SCD risk when post-MI LV dysfunction
      develops.

PMID- 11345394
TI  - Changing guidelines on conflict of interest.

PMID- 11345395
TI  - The need for the in(ter)dependent investigator.

PMID- 11345396
TI  - The effects of biphasic and conventional monophasic defibrillation on
      postresuscitation myocardial function.

PMID- 11345397
TI  - Effectiveness of BiPAP for congestive heart failure.

PMID- 11345398
TI  - IgG2 class red cell antibodies and autoimmune haemolysis.
AB  - AIM: To examine the role of IgG2 red cell autoantibodies in autoimmune
      haemolysis. METHODS: Study of immunohaematology case records. RESULTS: Six
      patients had only IgG2 autoantibodies detected by direct antiglobulin testing and
      in red cell eluates; two individuals, whose red cells were also coated with
      complement, suffered from autoimmune haemolytic anaemia. CONCLUSIONS: IgG2
      antibodies are found alone in <1% of patients with warm autoantibodies and even
      more rarely cause red cell destruction. Several factors are important for
      inducing haemolysis. They include allele differences in the FCRIIA genes encoding
      for the FcyRII receptors--an allele with high affinity for IgG2 is needed for
      haemolysis. Topography of red cell antigens may also be significant; IgG2 is a
      relatively inflexible molecule and access of effector cell Fc receptors to the
      recognition sites on the IgG2 might be impossible unless the antigens are on, or
      proud to, the red cell surface. On rare occasions, IgG2 activates complement (as
      in our patients with active haemolysis); the synergistic effect between red cell
      bound immunoglobulins and C3 in causing haemolysis is well recognised.

PMID- 11345399
TI  - T-cell-rich B-cell lymphoma: a clinicopathologic study of eight cases.
AB  - T-cell-rich B-cell lymphoma (TCRBCL) is a recently recognized and ill-defined
      form of non-Hodgkin's lymphoma (NHL), with no generally accepted diagnostic
      criteria and with limited information regarding its incidence, cellular origin,
      morphologic spectrum and biologic behavior. The recent findings suggest that
      TCRBCL could be a biologically distinct disease characterized by male
      preponderance, advanced-stage disease initially and high incidence of extranodal
      localization, especially in the bone marrow. For the time being, proper diagnosis
      rests on the immunohistochemical identification of the scattered large malignant
      B-cells amid a sea of small reactive T-lymphocytes. In this study, the
      clinicopathologic features of 8 patients (pts) with TCRBCL are presented. The
      male to female ratio was 5/3, and the median age was 52 years (32-67). The
      disease was advanced in most patients: 5 pts with stage IV and 2 pts with stage
      III. The patients presented with generalized lymphadenopathy (5), splenomegaly
      and/or hepatomegaly (4) and bone marrow involvement (4). The diagnosis of TCRBCL
      was initially established in 6 pts, while the remaining 2 pts were initially
      diagnosed as having Hodgkin's disease (of mixed cellularity in 1 pt and
      lymphocytic predominance in another). Revision of the 2 samples comprising
      immunohistochemistry enabled diagnosis of TCRBCL. Immunohistomorphologically the
      present series can be differentiated from other types of lymphoma such as
      lymphocyte-predominant Hodgkin's disease and peripheral T-cell lymphoma.

PMID- 11345400
TI  - Obstetric prognosis of the gestational thrombocytopenia.
AB  - To define clinical outcomes of marked gestational thrombocytopenia (GT)
      (<100,000/mm3) we identified twenty-nine infants born to 28 pregnancies at 26
      women with GT among 8,364 deliveries during the years 1993- 1999. Cordocentesis
      was performed in 7 mothers with platelet counts less than 75,000/mm3. Cord blood
      platelet count was checked in all cases at delivery. The most significant
      decrease of platelet count in pregnancy with GT was less than 50,000/mm3 in 6
      pregnancies (21.4%) and between 50,000 and 100,000/mm3 in 22 pregnancies (78.6%).
      In pregnancies with GT, 2 neonates (6.9%) had mild thrombocytopenia and 1 neonate
      (3.4%) moderate thrombocytopenia. Severe thrombocytopenia was not observed in any
      neonate born to mothers with GT. There were no cases of coagulation disturbance
      at delivery or in the postpartum period. Fourteen cases for which follow-up was
      carried out recovered platelet counts to more than 100,000/mm3 within one month
      postpartum. Two patients who became pregnant twice noticed recurrence of GT. In
      conclusion, GT is not associated with bleeding diathesis in the mother, resolves
      spontaneously during the postpartum period, and can recur in subsequent
      gestations, and the association of severe fetal/neonatal thrombocytopenia is very
      rare. No intervention is necessary during pregnancy or delivery, apart from a
      careful maternal and fetal surveillance if there is no obstetric indication.

PMID- 11345401
TI  - Selectins in normal pregnancy, pre-eclampsia and missed abortus.
AB  - Selectins, are known to be increased in the serum of patients with pre-eclampsia,
      indicating that these molecules are possible markers of endothelial cell injury.
      In this study, we investigated P, E and L selectin levels in normal pregnancy,
      pre-eclampsia, and missed abortus. Plasma P and L selectins levels were
      significantly higher in normal pregnancy and pre-eclampsia than healthy controls;
      but plasma concentrations of E selectins were not different between these groups.
      Plasma P selectin was significantly higher in pre-eclampsia than normal
      pregnancy. Plasma concentrations of all selectins were significantly higher in
      missed abortus than healthy control. L selectin levels were higher in pre
      eclampsia and missed abortus than normal pregnancy. We found the levels of
      selectins were increased in pre-eclampsia and missed abortus. Although selectins
      were suspected to play a role in the pathogenesis of pre-eclampsia, in
      conjunction with previous studies, we thought that elevated selectin levels are a
      non-specific consequence of endothelial injury rather than being a cause.

PMID- 11345402
TI  - Thrombotic thrombocytopenic purpura--possibilities of treatment and results.
AB  - Results of treatment of 13 patients fulfilling the criteria for TTP are
      presented. Thrombocytopenia was present in all patients (100%). Eleven of 13
      patients (84.6%) had conciousness disorder, and seven of 13 patients (53.8%) had
      renal impairment. Immunosuppressive therapy with plasmapheresis and replacement
      of removed volume with fresh frozen plasma in a dosage of 25 ml/kg body weight
      resulted in statistically significant increase of platelet count (p = 0.0033),
      and significant improvement of consciousness as defined by increased Glasgow Coma
      Score (GCS) (p = 0.0524). In two patients, renal function recovered and, in one
      patient, hemodialysis was no longer needed. This improvement in a small patient
      group has no statistical significance.

PMID- 11345403
TI  - Increased risk for cancer in multiple myeloma patients and their first-degree
      relatives.
AB  - Analyzing data of 125 multiple myeloma patients, the authors found a 40-fold
      increased tumor incidence among the patients and their first-degree relatives as
      compared to the average population. These tumors were the same as those usually
      found among Hungarians. There was no difference as to the patient's blood group
      antigens in the families of myeloma patients with or without other tumor. IgA
      type disease was found to be relatively more frequent in the group of patients
      who had tumor besides myeloma. In a prospective study, authors could not find
      mutation of suppressor gene p53 in 14 patients and their 16 healthy first-degree
      relatives. This may indicate that there is no p53 suppressor gene alteration
      responsible for the high-risk condition for tumorgenesis in this population.

PMID- 11345404
TI  - Bone-specific alkaline phosphatase protein, total alkaline phosphatase activity
      and lactate dehydrogenase in sera of patients with sickle cell disease.
AB  - Serum bone-specific alkaline phosphatase protein (bAP) was evaluated as indicator
      of bone turnover by immunoradiometric assay (IRMA) in twenty patients with sickle
      cell disease and in twenty healthy control subjects. Serum bAP was also compared
      with serum total alkaline phosphatase activity and serum lactate dehydrogenase in
      the same group. The concentrations of serum bAP and serum lactate dehydrogenase
      were significantly higher in the study group than in the control group (p < 0.05,
      p < 0.01, respectively). The serum total alkaline phosphatase activity showed no
      significant difference with the control healthy subjects. There was no
      correlation between serum bAP and total alkaline phosphatase or lactate
      dehydrogenase levels in the patient group. In conclusion, serum bAP protein
      measured by IRMA can be considered a sensitive marker of bone turnover and could
      be especially useful as valuable non-invasive biochemical marker for identifying
      sickle cell patients with skeletal complications.

PMID- 11345405
TI  - High prevalence of G6PD deficiency in Vataliya Prajapati community in western
      India.
AB  - OBJECTIVE: Sporadic cases of drug-induced haemolytic anaemia due to glucose-6
      phosphate dehydrogenase (G6PD) deficiency in patients belonging to Vataliya
      Prajapati community prompted us to study the prevalence of G6PD deficiency in the
      community. METHODS: Screening for G6PD deficiency was carried out using the
      dichlorophenol-indophenol (DPIP) dye decolorization method. RESULTS: A total of
      471 individuals were screened. Of these, 385 unrelated individuals were
      considered to calculate the prevalence of G6PD deficiency. Among 272 unrelated
      males, 76 persons (27.94%) and among 113 unrelated females, 11 individuals
      (9.73%) were found to be G6PD deficient. A quantitative assay on 41 of the G6PD
      deficient samples showed the enzyme activity ranged from 0-0.5 unit/ml RBC/min.
      CONCLUSION: The prevalence of G6PD deficiency in Vataliya Prajapatis community
      was found to be the highest ever reported in the Indian caste-groups population
      studied so far.

PMID- 11345406
TI  - Serum KL-6 levels in haematologic malignancies and their clinical application.

PMID- 11345407
TI  - Expression of human interleukin-18 antigen in leukemia cells in a patient with
      acute mixed lineage leukemia.

PMID- 11345408
TI  - Detection of CD55 and/or CD59 deficient red cell populations in patients with
      aplastic anaemia, myelodysplastic syndromes and myeloproliferative disorders.
AB  - Paroxysmal nocturnal haemoglobinuria (PNH) is an acquired clonal stem cell
      disorder characterized by intravascular haemolysis, venous thrombosis, marrow
      hypoplasia, frequent episodes of infection, and rarely leukaemic conversion. At
      the cellular level, PNH is characterized by the decrease or absence of
      glycosylphosphatidylinositol (GPI)-anchored molecules, such as CD55 and CD59,
      from the cell surface. PNH-like clones have been described in various
      haematological disorders. The link between PNH and aplastic anaemia (AA) has been
      established but the relationship of PNH with myelodysplastic syndromes (MDS) or
      myeloproliferative disorders (MPD) remains unclear. In this study, the presence
      of CD55 and/or CD59 defective (PNH-like) red cell populations was evaluated in 21
      patients with AA, 133 with MDS, 197 with MPD, 7 with PNH and in 121 healthy blood
      donors using the Sephacryl Gel Test microtyping system. Red cell populations
      deficient in both molecules CD55 and CD59 were detected in 33.3% of AA patients,
      in 16.5% of MDS patients (50% with hypoplastic bone marrow), in 14.2% of MPD
      patients (more often in essential thrombocythemia, 21.2%) and in all PNH
      patients. CD55 deficient red cell populations were found in 14.2% of patients
      with AA, 12.7% of patients with MDS and 21.3% of patients with MPD. CD59
      deficient populations were found in 9.5% of AA patients, 2.2% of MDS patients and
      2% of MPD patients. These results indicate an association between PNH, AA and MDS
      or even between PNH and MPD. Further investigation is necessary to work out the
      mechanisms of this association, and to define classification criteria for
      borderline cases, where diagnosis is difficult.

PMID- 11345410
TI  - Erythema annulare centrifugum as the presenting sign of CD 30 positive anaplastic
      large cell lymphoma--association with disease activity.
AB  - Erythema annulare centrifugum is a figurate erythema that has been associated
      with many different entities. A case of erythema annulare centrifugum related to
      non-Hodgkin's lymphoma in a 38-year-old woman is described in this case report.
      Response of the lymphoma to a combination chemotherapy was accompanied by
      disappearance of skin lesions. When therapy was discontinued, both disorders
      recurred, and both responded to reinstitution of a different chemotherapy
      regimen. To our knowledge, this case is the first reported association of
      erythema annulare centrifugum and non-Hodgkin's lymphoma in the medical
      literature.

PMID- 11345409
TI  - Clinical activity of the new triazole drug voriconazole (UK 109, 496) against
      disseminated hepatosplenic aspergillosis in a patient with relapsed leukemia.
AB  - There is presently a limited antifungal armamentarium comprising amphotericin and
      the azoles, fluconazole and itraconazole. In vitro studies have shown efficacy of
      the new drug, voriconazole, against a wide range of fungi, including most species
      of Candida and Aspergillus. We review here a case report of a young boy with
      acute myeloid leukemia who developed disseminated hepatosplenic aspergillosis. He
      failed therapy with itraconazole, amphotericin B and liposomal amphotericin. As
      he also had relapsed leukemia, there was a great urgency to control this
      infection in order to facilitate the administration of cancer chemotherapy.
      Voriconazole was given with good response resulting in virtual disappearance of
      all scan evidence of aspergillosis.

PMID- 11345411
TI  - Combination chemotherapy with theophylline in chronic lymphocytic leukemia.

PMID- 11345412
TI  - Insecticide-induced behavioral responses of Anopheles minimus, a malaria vector
      in Thailand.
AB  - This study was designed to determine the behavioral responses of 2 test
      populations of Anopheles minimus females to DDT at 2 g/m2, deltamethrin at 0.0625
      g/m2, and lambdacyhalothrin at 0.0369 g/m2 using an improved excito-repellency
      escape chamber. One test population was colonized in 1993 and referred to as a
      young colony. The 2nd field test population was collected from Ta-Soa County, Tri
      Yok District, Kanchanaburi Province. in western Thailand and referred to as a
      wild population. Results showed that females of both young and wild test
      populations rapidly escaped from direct contact with DDT, deltamethrin, and
      lambdacyhalothrin. Lambdacyhalothrin exhibited the strongest irritant effect on
      female mosquitoes, followed by DDT and deltamethrin. Fewer females escaped from
      test chambers without direct contact with treated surfaces but the response was
      significantly different from that of the controls (P < 0.05). The noncontact
      response is indicative of a noncontact repellent action. Both contact irritancy
      and noncontact repellency are involved in An. minimus escape responses.
      Experimental hut studies that include monitoring of house-entering populations of
      An. minimus are needed for a meaningful assessment of noncontact repellent
      actions.

PMID- 11345413
TI  - Efficacy of ground-applied ultra-low-volume malathion on honey bee survival and
      productivity in open and forest areas.
AB  - A study was conducted to determine the efficacy of ground ultra-low-volume
      malathion sprays on honey bee (Apis mellifera L.) apiaries in open and forested
      areas downwind from the spray route. Impact on colonies 7.6, 15.2, 47.7, and 91.4
      m downwind from sprays was assessed by recording individual bee mortality 12 and
      36 h after treatment. In addition, hives were weighed before as well as during
      the study and cluster counts were conducted at each hive to determine colony
      strength before and after treatment. Spray drift was monitored by the use of
      caged mosquito (Culex quinquefasciatus Say) mortality and deposition on filter
      paper. During the study, significant bee mortality in the open area occurred on 2
      occasions at 7.6 m (16.8 +/- 4.3 bees, 11.8 +/- 7.0 bees) and at 15.2 m (6.5 +/-
      1.7 bees, 5.3 +/- 1.5 bees). Significant mortality in the forested area was
      observed only once and consisted of 2 bees at 7.6 m. In each case where bee
      mortality occurred, spray deposits on filter papers had exceeded 400 ng/cm2.
      Although mortality of caged mosquitoes indicated that malathion drifted through
      the study areas, little correlation was apparent between mortality and spray
      deposition on filter paper.

PMID- 11345414
TI  - Susceptibility of sand flies to selected insecticides in North Africa and the
      Middle East.
AB  - The purpose of this study was to determine the baseline susceptibility of 4
      species of phlebotomine sand flies from North Africa and the Middle East to
      various insecticides. Susceptibility was determined using the World Health
      Organization test kits for measuring resistance in mosquitoes exposed to
      insecticide-impregnated papers. Fifty, 90, and 99% lethal doses were calculated
      for bendiocarb, cyfluthrin, DDT, malathion, permethrin, and resmethrin on
      Phlebotomus bergeroti, P. langeroni, P. papatasi. and P. sergenti. The least
      toxic insecticide to all species was DDT, followed by malathion and permethrin in
      order of increasing toxicity. Cyfluthrin was the most toxic to P. langeroni and
      P. papatasi, followed by resmethrin and bendiocarb in order of decreasing
      toxicity. Resmethrin exhibited the highest toxicity to P. bergeroti followed by
      cyfluthrin and bendiocarb, whereas bendiocarb was most toxic to P. sergenti,
      followed by cyfluthrin and resmethrin in order of decreasing toxicity. An attempt
      was made to obtain data for deltamethrin, but close response data were
      insufficient to determine regression lines for this insecticide on these species.
      However, analysis of preliminary data indicated that deltamethrin is highly toxic
      to these sand flies.

PMID- 11345415
TI  - Indoor thermal fogging application of pesguard FG 161, a mixture of d
      tetramethrin and cyphenothrin, using portable sprayer against vector mosquitoes
      in the tropical environment.
AB  - Indoor bioefficacy of the thermal fogging application of Pesguard FG 161, a
      formulation containing both knockdown and killing agents (active ingredient [AI]:
      d-tetramethrin 4% [w/w] and cyphenothrin 12% [w/w]) was compared with Resigen5
      (AI: s-bioallethrin 0.8% [w/w], permethrin 125/75] 18.7% [w/w], and piperonyl
      butoxide 16.8% [w/w]), another pyrethroid formulation, as larvicides and
      adulticides against Aedes aegypti, Aedes albopictus, Anopheles sinensis, and
      Culex quinquefasciatus using a portable Agrofog AF35 sprayer indoors in houses on
      Penang Island, Malaysia. Pesguard FG 161 at the concentrations tested was
      effective against all 4 mosquito species tested. The water-based Pesguard FG 161
      performed far better as a larvicide than the diesel-based formulation. Resigen
      was also effective as a larvicide and adulticide against all 4 mosquito species
      tested. Larvae of Ae. aegypti were most susceptible to water-based Pesguard FG
      161, followed by Cx. quinquefasciatus, An. sinensis, and Ae. albopictus. Even at
      the lowest concentrations tested, Pesguard FG 161 showed adequate adulticidal
      properties. At higher dosages, water-based Pesguard FG 161 proved effective as a
      larvicide against all 4 mosquito species.

PMID- 11345416
TI  - Recovery of commercially produced Bacillus thuringiensis var. israelensis and
      Bacillus sphaericus from tires and prevalence of bacilli in artificial and
      natural containers.
AB  - We conducted surveys to identify the species of spore-forming bacteria present in
      natural and artificial containers. Most of our samples came from Illinois.
      Identification was based on the cellular fatty acid composition of the bacterial
      cell wall. In addition, we utilized a custom database for commercially produced
      strains of Bacillus thuringiensis var. israelensis (Bti) and B. sphaericus, to
      differentiate between larvicidal isolates with commercial or native origin.
      Native Bti was present at low levels in almost all habitats but was not recovered
      from bromeliads and metal containers. In temporary woodland pools, 27.9% of the
      colonies recovered were native Bti. We did not recover larvicidal B. sphaericus
      in untreated habitats. VectoBac and VectoLex were applied to tires containing
      water and the tires were sampled 3 months and 9 months after treatment. Isolates
      of Bti and B. sphaericus with commercial origin were recovered as long as 9
      months after application. We noticed numerous cadavers of Aedes triseriatus in
      several tires 9 months after treatment with VectoBac. We could not determine if
      this mortality resulted from recycling of Bti in these tires or whether
      insecticidal crystal proteins from the original treatment were resuspended.
      Bacillus thuringiensis var. israelensis isolates with commercial ancestry were
      recovered from untreated tires 9 months after application. Isolates of larvicidal
      B. sphaericus that differed from the bacteria in VectoLex were also recovered
      from untreated tires.

PMID- 11345417
TI  - Field evaluation of repellents containing deet and AI3-37220 against Anopheles
      koliensis in Papua New Guinea.
AB  - The repellent 1-(3-cyclohexen-1-yl-carbonyl)-2-methylpiperidine (AI3-37220) was
      compared with 2 formulations of diethylmethylbenzamide (deet) for its
      effectiveness in protecting 4 humans against the bites of Anopheles koliensis
      mosquitoes at a village in Central Province, Papua New Guinea. A mean of 77.2 +/-
      10.5 bites/human/10 min of An. koliensis was collected on ethanol-treated
      (control) volunteers, a much higher density than most previous studies with
      Anopheles sp. mosquitoes. The protection provided by all repellents did not last
      long. Both 25% A13-37220 in ethanol and a formulation containing 35% deet in a
      gel provided >95% protection for only 2 h. A formulation of 25% deet in ethanol
      provided only 93% protection 1 h after repellent application and 39% protection 5
      h after application.

PMID- 11345418
TI  - Impact of a 26-month Bacillus sphaericus trial on the preimaginal density of
      Culex quinquefasciatus in an urban area of Recife, Brazil.
AB  - A field trial using the entomopathogen Bacillus sphaericus against Culex
      quinquefasciatus was conducted in a district of Recife, Brazil, an area with a
      high prevalence of lymphatic filariasis. In this urban area more than 2,500 Cx.
      quinquefasciatus breeding sites within a 1.2-km2 area were found and subsequently
      submitted to a long-term treatment with B. sphaericus. To evaluate the impact of
      treatment on the densities of Cx. quinquefasciatus preimaginal forms, 26 breeding
      sites, representative of the major site types found in that area, were monitored
      for 3 years. Parameters such as mean and maximum densities of larval population
      as well as the frequency of infested sites were recorded before, during, and
      after the trial. The level of each parameter was greatly reduced during the
      treatment period, particularly in the 2nd treatment year. A low density of Cx.
      quinquefasciatus was also maintained throughout the last year, in the absence of
      treatment. Analysis of the data reported here confirms B. sphaericus as a very
      effective larvicide against Cx. quinquefasciatus despite the optimal
      environmental conditions for mosquito proliferation in the urban area of Recife.

PMID- 11345419
TI  - Revised list of abbreviations for genera and subgenera of Culicidae (Diptera) and
      notes on generic and subgeneric changes.
AB  - Recent generic and subgeneric changes in family Culicidae are summarized and a
      revised and updated list of abbreviations for the currently recognized 39 genera
      and 135 subgenera of the family is provided.

PMID- 11345420
TI  - The energetic costs of diving in Aedes aegypti and Aedes albopictus pupae.
AB  - Undisturbed mosquito pupae rest at the water surface and respond to passing
      shadows or vibrations by diving. Pupae do not feed and rely solely on energy
      stored from the larval stage. The ability of a newly emerged adult mosquito to
      survive, and therefore to transmit disease, depends on these energy reserves.
      Earlier studies of diving behavior in Aedes aegypti, Ae. albopictus, and Ae.
      triseriatus pupae provided evidence that pupae sense their state of buoyancy and
      modify their diving behavior accordingly. With strong stimulation pupae tend to
      dive to a depth where they become neutrally or negatively buoyant and commonly
      rest on the bottom. This behavior, as well as the tendency to rest when not
      disturbed, may logically be viewed as energy-conserving. The results of these
      studies also generated the hypothesis that the diving behavior displayed by these
      container-breeding mosquitoes helps them avoid being washed from their container
      by overflowing water during rainfall. Rainfall stimulates diving and logically,
      prolonged, heavy rainfall stimulates excessive diving, a likely drain on energy
      reserves. Our objectives were to determine, in Ae. aegypti and Ae. albopictus,
      the energetic costs associated with resting behavior, with frequent diving, and
      with buoyancy reduction. Using survival rate, mean survival after adult
      emergence, and measurement of total calories, we found a clear energetic cost
      associated with frequent diving. In contrast, relative to diving, essentially no
      energy cost was associated with buoyancy reduction, that is, pupae behave in
      response to variations in buoyancy in a way that does not impact significantly on
      energy reserves.

PMID- 11345421
TI  - Evaluation of 1-octen-3-ol, carbon dioxide, and light as attractants for
      mosquitoes associated with two distinct habitats in North Carolina.
AB  - Field studies were conducted in North Carolina to determine the responses of
      mosquitoes found in salt marsh and inland creek flood plain areas to 1-octen-3-ol
      (octenol), carbon dioxide (CO2), and light in various combinations with Centers
      for Disease Control (CDC) light traps. Over 56,000 adult mosquito specimens of 12
      species in 4 genera were collected in the salt marsh. They exhibited a general
      response pattern of octenol + CO2 + light > CO2 + light = octenol + CO2 > octenol
      + light > octenol alone. Significantly, more Aedes sollicitans, Ae.
      taeniorhynchus, Anopheles bradleyi, and Culex salinarius were attracted to
      octenol + CO2 + light than to CO2 + light. Over 19,000 specimens of 24 species in
      7 genera were collected in the inland creek flood plain. Although the response
      patterns to the attractants were similar to those in the salt marsh area, there
      was no significant difference between octenol + CO2 + light and CO2 + light.
      Aedes vexans, An. crucians, and An. punctipennis were attracted nearly equally to
      these two attractant combinations. These studies demonstrate that responses to
      combinations of these attractants are species specific. However, different
      combinations of attractants can significantly increase the collection of targeted
      species important in arbovirus transmission. The use of these combinations would
      be very beneficial in mosquito-borne virus surveillance studies. The use of
      octenol by itself or in conjunction with light was found the least useful for
      collecting mosquitoes in both habitats.

PMID- 11345422
TI  - Daily survival and human blood index of Anopheles sinensis, the vector species of
      malaria in Korea.
AB  - To evaluate the vector efficiency of Anopheles sinensis in transmitting vivax
      malaria in the northern part of Gyonggi-do, South Korea, daily survival and
      feeding host preferences were studied during the period of June-October 1999.
      Ovaries of unfed and freshly fed An. sinensis females were dissected and parity
      or nulliparity were observed. The parous rates were 75.2% in July, 56.5% in
      August, 78.5% in September, and 60.0% in October at Gusan-dong, Goyang-si,
      Gyonggi-do. The average probability of daily survival was 0.890. To determine the
      host feeding patterns of An. sinensis, outdoor-resting bloodfed mosquitoes were
      collected, and the sources of the blood meals were analyzed by enzyme-linked
      immunosorbent assay, using 6 different animal immunoglobulin G antibodies. Out of
      305 blood meals tested, 0.7% were positive from humans, 89.8% from bovines, 3.3%
      from swine, 0.7% from dogs, 1.6% from chickens, and 0.7% from bovines and swine
      mixed. No blood meals were positive from mice. Though the vector efficiency of
      An. sinensis was poor because of a low human blood index and a moderate rate of
      daily survival, vectorial capacity would be high because of high density of the
      population.

PMID- 11345423
TI  - Arbovirus surveillance in South Carolina, 1996-98.
AB  - Arboviruses isolated and identified from mosquitoes in South Carolina (USA) are
      described, including new state records for eastern equine encephalitis virus
      (EEE), St. Louis encephalitis virus (SLE), Flanders virus, Tensaw virus (TEN),
      and a variant of Jamestown Canyon virus (JC). Mosquitoes were collected at 52
      locations in 30 of 46 South Carolina counties beginning in June 1996, and ending
      in October 1998, and tested for arboviruses. Of 1,329 mosquito pools tested by
      virus isolation (85,806 mosquitoes representing 34 mosquito species or
      complexes), 15 pools were positive. Virus isolations included EEE from 1 pool
      each of Anopheles crucians complex and Culex erraticus; a variant of JC from 1
      pool of An. crucians complex; a California serogroup virus from 1 pool of Aedes
      atlanticus/tormentor; TEN from 5 pools of An. crucians complex and 1 pool each of
      Culex salinarius and Psorophora ciliata; Flanders virus from 1 pool of Culiseta
      melanura; and Potosi virus from 1 pool each of Aedes vexans, Coquillettidia
      perturbans, and Psorophora columbiae. Of 300 mosquito pools tested by antigen
      capture assay for EEE and SLE (14,303 mosquitoes representing 16 mosquito species
      or complexes), 21 were positive for EEE and I was positive for SLE. Positive EEE
      mosquito pools by antigen-capture assay included An. crucians complex (14 pools),
      Anopheles punctipennis (1 pool), Anopheles quadrimaculatus (1 pool), Cq.
      perturbans (4 pools), and Cs. melanura (1 pool). One pool of Cx. salinarius was
      positive for SLE by antigen-capture assay. Arbovirus-positive mosquito pools were
      identified from 12 South Carolina counties, all located in the Atlantic Coastal
      Plain, and from 4 of 8 Carolina bays surveyed.

PMID- 11345424
TI  - First records of Culex gelidus from Australia.
AB  - Culex gelidus Theobald was recorded for the 1st time in Australia in May 1999
      from 2 locations (Brisbane and Mackay, Queensland) approximately 820 km apart.
      Larval samples were collected from a semi-permanent freshwater swamp and an open
      drain and reared to adults in laboratories. Implications for Australia are
      discussed.

PMID- 11345425
TI  - Evaluation of liquid Bacillus thuringiensis var. israelensis products for control
      of Australian Aedes arbovirus vectors.
AB  - Laboratory bioassay studies were conducted in southeast Queensland, Australia, on
      the efficacy of Teknar, VectoBac 12AS, and Cybate (active ingredient: 1,200
      international toxic units Bacillus thuringiensis var. israelensis [Bti]) against
      3rd instars of the arbovirus vectors Aedes aegypti, Ae. notoscriptus, Ae.
      vigilax, and Ae. camptorhynchus. Probit analyses were then used to determine LD50
      (median lethal dose), LD50, and lethal dose ratios (LDR). Aedes aegypti and Ae.
      notoscriptus, both container-habitat species, tolerated the highest Bti
      concentrations compared with saltmarsh Ae. vigilax and Ae. camptorhynchus. For
      example, the LDR for Ae. vigilax versus Ae. notoscriptus exposed to Cybate was
      0.14 (95% confidence limit [CL] 0.03-0.61). Similarly, the Cybate LDR for Ae.
      camptorhynchus versus Ae. notoscriptus was 0.22 (95% CL 0.07-0.70). Teknar
      produced similar results with an LDR of 0.21 (95% CL 0.04-1.10) for Aedes vigilax
      versus Aedes notoscriptus. Differences in product efficacy were found when tested
      against the 2 container-breeding species. Cybate was less effective than Teknar
      with LDRs of 1.55 (95% CL 0.65-3.67) and 1.87 (95% CL 0.68-5.15) for Aedes
      aegypti and Ae. notoscriptus, respectively. The significant differences in
      susceptibility between mosquito species and varying efficacy between products
      highlight the importance of evaluating concentration-response data prior to
      contracting with distributors of mosquito control products. This information is
      crucial to resistance management strategies.

PMID- 11345426
TI  - Differential predation of the planarian Dugesia tigrina on two mosquito species
      under laboratory conditions.
AB  - Two experiments were performed on the predation of the planarian Dugesia tigrina
      (Girard) upon 2 mosquito prey species, Aedes albopictus and Culex
      quinquefasciatus. Bioassays were carried out in sectioned tires with 2 liters of
      water. In the 1st experiment, predation was evaluated using 4, 8, and 12 mature
      planarians against 40 2nd-stage larvae of each mosquito species alone. In the 2nd
      experiment, the same 3 predator densities were used with a pool composed of 20
      2nd-stage larvae of each mosquito species. In the 1st experiment, final corrected
      mortality of Ae. albopictus reached 89.1, 98.8, and 99.6% and final corrected
      mortality of Cx. quinquefasciatus reached 29.4, 48.0, and 53.0%, respectively,
      with 4, 8, and 12 planarians. In the 2nd experiment and when subjected to the
      density of 4 planarians, Ae. albopictus was more susceptible to predation, with a
      selectivity index of 0.87, whereas this index was 0.13 for Cx. quinquefasciatus.
      Predation was more intensive during the 1st 4 days of the experiments, when most
      larvae were in the 2nd and 3rd stages. We observed that Cx. quinquefasciatus
      larvae were faster than Ae. albopictus in reacting to planarian contacts,
      resulting in more success in escaping from the predator attacks.

PMID- 11345427
TI  - Phoresy of a louse (Mallophaga: Philopteridae) on a mosquito from Cali, Colombia.
AB  - A case of phoresy of a female Sturnidoecus sp. on the wing of a female Culex
      nigripalpus in Cali, Valle is presented. The phenomenon in southwestern Colombia
      is discussed.

PMID- 11345428
TI  - Beaver ponds in upstate new york as a source of anthropophilic mosquitoes.
AB  - Surveys for anthropophilic mosquitoes conducted over a 30-year period in
      proximity of beaver ponds in 3 research sites in Otsego County, New York,
      indicate that none of the ponds seemed to support significant populations of
      permanent water mosquitoes. The only site sampled before impoundment previously
      had supported large populations of Aedes punctor and Aedes stimulans and lesser
      numbers of other "northern Aedes"-type anthropophilic species.

PMID- 11345429
TI  - Geometric nomenclature and classification of RNA base pairs.
AB  - Non-Watson-Crick base pairs mediate specific interactions responsible for RNA-RNA
      self-assembly and RNA-protein recognition. An unambiguous and descriptive
      nomenclature with well-defined and nonoverlapping parameters is needed to
      communicate concisely structural information about RNA base pairs. The
      definitions should reflect underlying molecular structures and interactions and,
      thus, facilitate automated annotation, classification, and comparison of new RNA
      structures. We propose a classification based on the observation that the planar
      edge-to-edge, hydrogen-bonding interactions between RNA bases involve one of
      three distinct edges: the Watson-Crick edge, the Hoogsteen edge, and the Sugar
      edge (which includes the 2'-OH and which has also been referred to as the Shallow
      groove edge). Bases can interact in either of two orientations with respect to
      the glycosidic bonds, cis or trans relative to the hydrogen bonds. This gives
      rise to 12 basic geometric types with at least two H bonds connecting the bases.
      For each geometric type, the relative orientations of the strands can be easily
      deduced. High-resolution examples of 11 of the 12 geometries are presently
      available. Bifurcated pairs, in which a single exocyclic carbonyl or amino group
      of one base directly contacts the edge of a second base, and water-inserted
      pairs, in which single functional groups on each base interact directly, are
      intermediate between two of the standard geometries. The nomenclature facilitates
      the recognition of isosteric relationships among base pairs within each geometry,
      and thus facilitates the recognition of recurrent three-dimensional motifs from
      comparison of homologous sequences. Graphical conventions are proposed for
      displaying non-Watson-Crick interactions on a secondary structure diagram. The
      utility of the classification in homology modeling of RNA tertiary motifs is
      illustrated.

PMID- 11345430
TI  - Optimization and optimality of a short ribozyme ligase that joins non-Watson
      Crick base pairings.
AB  - A small ribozyme ligase (L1) selected from a random sequence population appears
      to utilize non-Watson-Crick base pairs at its ligation junction. Mutational and
      selection analyses confirmed the presence of these base pairings. Randomization
      of the L1 core and selection of active ligases yielded highly active variants
      whose rates were on the order of 1 min(-1). Base-pairing covariations confirmed
      the general secondary structure of the ligase, and the most active ligases
      contained a novel pentuple sequence covariation. The optimized L1 ligases may be
      optimal within their sequence spaces, and minimal ligases that span less than 60
      nt in length have been engineered based on these results.

PMID- 11345431
TI  - Generating new ligand-binding RNAs by affinity maturation and disintegration of
      allosteric ribozymes.
AB  - Allosteric ribozymes are engineered RNAs that operate as molecular switches whose
      rates of catalytic activity are modulated by the binding of specific effector
      molecules. New RNA molecular switches can be created by using "allosteric
      selection," a molecular engineering process that combines modular rational design
      and in vitro evolution strategies. In this report, we describe the
      characterization of 3',5'-cyclic nucleotide monophosphate (cNMP)-dependent
      hammerhead ribozymes that were created using allosteric selection (Koizumi et
      al., Nat Struct Biol, 1999, 6:1062-1071). Artificial phylogeny data generated by
      random mutagenesis and reselection of existing cGMP-, cCMP-, and cAMP-dependent
      ribozymes indicate that each is comprised of distinct effector-binding and
      catalytic domains. In addition, patterns of nucleotide covariation and direct
      mutational analysis both support distinct secondary-structure organizations for
      the effector-binding domains. Guided by these structural models, we were able to
      disintegrate each allosteric ribozyme into separate ligand-binding and catalytic
      modules. Examinations of the independent effector-binding domains reveal that
      each retains its corresponding cNMP-binding function. These results validate the
      use of allosteric selection and modular engineering as a means of simultaneously
      generating new nucleic acid structures that selectively bind ligands.
      Furthermore, we demonstrate that the binding affinity of an allosteric ribozyme
      can be improved through random mutagenesis and allosteric selection under
      conditions that favor tighter binding. This "affinity maturation" effect is
      expected to be a valuable attribute of allosteric selection as future endeavors
      seek to apply engineered allosteric ribozymes as biosensor components and as
      controllable genetic switches.

PMID- 11345433
TI  - The hammerhead cleavage reaction in monovalent cations.
AB  - Recently, Murray et al. (Chem Biol, 1998, 5:587-595) found that the hammerhead
      ribozyme does not require divalent metal ions for activity if incubated in high
      (> or =1 M) concentrations of monovalent ions. We further characterized the
      hammerhead cleavage reaction in the absence of divalent metal. The hammerhead is
      active in a wide range of monovalent ions, and the rate enhancement in 4 M Li+ is
      only 20-fold less than that in 10 mM Mg2+. Among the Group I monovalent metals,
      rate correlates in a log-linear manner with ionic radius. The pH dependence of
      the reaction is similar in 10 mM Mg2+, 4 M Li+, and 4 M Na+. The exchange-inert
      metal complex Co(NH3)3+ also supports substantial hammerhead activity. These
      results suggest that a metal ion does not act as a base in the reaction, and that
      the effects of different metal ions on hammerhead cleavage rates primarily
      reflect structural contributions to catalysis.

PMID- 11345432
TI  - Comparison of the hammerhead cleavage reactions stimulated by monovalent and
      divalent cations.
AB  - Although the hammerhead reaction proceeds most efficiently in divalent cations,
      cleavage in 4 M LiCl is only approximately 10-fold slower than under standard
      conditions of 10 mM MgCl2 (Murray et al., Chem Biol, 1998, 5:587-595; Curtis &
      Bartel, RNA, 2001, this issue, pp. 546-552). To determine if the catalytic
      mechanism with high concentrations of monovalent cations is similar to that with
      divalent cations, we compared the activities of a series of modified hammerhead
      ribozymes in the two ionic conditions. Nearly all of the modifications have
      similar deleterious effects under both reaction conditions, suggesting that the
      hammerhead adopts the same general catalytic structure with both monovalent and
      divalent cations. However, modification of three ligands previously implicated in
      the binding of a functional divalent metal ion have substantially smaller effects
      on the cleavage rate in Li+ than in Mg2+. This result suggests that an
      interaction analogous to the interaction made by this divalent metal ion is
      absent in the monovalent reaction. Although the contribution of this divalent
      metal ion to the overall reaction rate is relatively modest, its presence is
      needed to achieve the full catalytic rate. The role of this ion appears to be in
      facilitating formation of the active structure, and any direct chemical role of
      metal ions in hammerhead catalysis is small.

PMID- 11345434
TI  - Distinct modes of mature and precursor tRNA binding to Escherichia coli RNase P
      RNA revealed by NAIM analyses.
AB  - We have analyzed by nucleotide analog interference mapping (NAIM) pools of
      precursor or mature tRNA molecules, carrying a low level of Rp-RMPalphaS (R = A,
      G, I) or Rp-c7-deaza-RMPalphaS (R = A, G) modifications, to identify functional
      groups that contribute to the specific interaction with and processing efficiency
      by Escherichia coli RNase P RNA. The majority of interferences were found in the
      acceptor stem, T arm, and D arm, including the strongest effects observed at
      positions G19, G53, A58, and G71. In some cases (interferences at G5, G18, and
      G71), the affected functional groups are candidates for direct contacts with
      RNase P RNA. Several modifications disrupt intramolecular tertiary contacts known
      to stabilize the authentic tRNA fold. Such indirect interference effects were
      informative as well, because they allowed us to compare the structural
      constraints required for ptRNA processing versus product binding. Our ptRNA
      processing and mature tRNA binding NAIM analyses revealed overlapping but
      nonidentical patterns of interference effects, suggesting that substrate binding
      and cleavage involves binding modes or conformational states distinct from the
      binding mode of mature tRNA, the product of the reaction.

PMID- 11345435
TI  - An essential protein-binding domain of nuclear RNase P RNA.
AB  - Eukaryotic RNase P and RNase MRP are endoribonucleases composed of RNA and
      protein subunits. The RNA subunits of each enzyme share substantial secondary
      structural features, and most of the protein subunits are shared between the two.
      One of the conserved RNA subdomains, designated P3, has previously been shown to
      be required for nucleolar localization. Phylogenetic sequence analysis suggests
      that the P3 domain interacts with one of the proteins common to RNase P and RNase
      MRP, a conclusion strengthened by an earlier observation that the essential
      domain can be interchanged between the two enzymes. To examine possible functions
      of the P3 domain, four conserved nucleotides in the P3 domain of Saccharomyces
      cerevisiae RNase P RNA (RPR1) were randomized to create a library of all possible
      sequence combinations at those positions. Selection of functional genes in vivo
      identified permissible variations, and viable clones that caused yeast to exhibit
      conditional growth phenotypes were tested for defects in RNase P RNA and tRNA
      biosynthesis. Under nonpermissive conditions, the mutants had reduced maturation
      of the RPR1 RNA precursor, an expected phenotype in cases where RNase P
      holoenzyme assembly is defective. This loss of RPR1 RNA maturation coincided, as
      expected, with a loss of pre-tRNA maturation characteristic of RNase P defects.
      To test whether mutations at the conserved positions inhibited interactions with
      a particular protein, specific binding of the individual protein subunits to the
      RNA subunit was tested in yeast using the three-hybrid system. Pop1p, the largest
      subunit shared by RNases P and MRP, bound specifically to RPR1 RNA and the
      isolated P3 domain, and this binding was eliminated by mutations at the conserved
      P3 residues. These results indicate that Pop1p interacts with the P3 domain
      common to RNases P and MRP, and that this interaction is critical in the
      maturation of RNase P holoenzyme.

PMID- 11345436
TI  - Sequence-specific interaction between HIV-1 matrix protein and viral genomic RNA
      revealed by in vitro genetic selection.
AB  - The human immunodeficiency virus type-1 matrix protein (HIV-1 MA) is a
      multifunctional structural protein synthesized as part of the Pr55 gag
      polyprotein. We have used in vitro genetic selection to identify an RNA consensus
      sequence that specifically interacts with MA (Kd = 5 x 10(-7) M). This 13-nt MA
      binding consensus sequence bears a high degree of homology (77%) to a region (nt
      1433-1446) within the POL open reading frame of the HIV-1 genome (consensus
      sequence from 38 HIV-1 strains). Chemical interference experiments identified the
      nucleotides within the MA binding consensus sequence involved in direct contact
      with MA. We further demonstrate that this RNA-protein interaction is mediated
      through a stretch of basic amino acids within MA. Mutations that disrupt the
      interaction between MA and its RNA binding site within the HIV-1 genome resulted
      in a measurable decrease in viral replication.

PMID- 11345437
TI  - The influence of downstream protein-coding sequence on internal ribosome entry on
      hepatitis C virus and other flavivirus RNAs.
AB  - Some studies suggest that the hepatitis C virus (HCV) internal ribosome entry
      site (IRES) requires downstream 5' viral polyprotein-coding sequence for
      efficient initiation of translation, but the role of this RNA sequence in
      internal ribosome entry remains unresolved. We confirmed that the inclusion of
      viral sequence downstream of the AUG initiator codon increased IRES-dependent
      translation of a reporter RNA encoding secretory alkaline phosphatase, but found
      that efficient translation of chloramphenicol acetyl transferase (CAT) required
      no viral sequence downstream of the initiator codon. However, deletion of an
      adenosine-rich domain near the 5' end of the CAT sequence, or the insertion of a
      small stable hairpin structure (deltaG = -18 kcal/mol) between the HCV IRES and
      CAT sequences (hpCAT) substantially reduced IRES-mediated translation. Although
      translation could be restored to both mutants by the inclusion of 14 nt of the
      polyprotein-coding sequence downstream of the AUG codon, a mutational analysis of
      the inserted protein-coding sequence demonstrated no requirement for either a
      specific nucleotide or amino acid-coding sequence to restore efficient IRES
      mediated translation to hpCAT. Similar results were obtained with the
      structurally and phylogenetically related IRES elements of classical swine fever
      virus and GB virus B. We conclude that there is no absolute requirement for viral
      protein-coding sequence with this class of IRES elements, but that there is a
      requirement for an absence of stable RNA structure immediately downstream of the
      AUG initiator codon. Stable RNA structure immediately downstream of the initiator
      codon inhibits internal initiation of translation but, in the case of hpCAT, did
      not reduce the capacity of the RNA to bind to purified 40S ribosome subunits.
      Thus, stable RNA structure within the 5' proximal protein-coding sequence does
      not alter the capacity of the IRES to form initial contacts with the 40S subunit,
      but appears instead to prevent the formation of subsequent interactions between
      the 40S subunit and viral RNA in the vicinity of the initiator codon that are
      essential for efficient internal ribosome entry.

PMID- 11345438
TI  - A short fragment of 23S rRNA containing the binding sites for two ribosomal
      proteins, L24 and L4, is a key element for rRNA folding during early assembly.
AB  - Previously we described an in vitro selection variant abbreviated SERF (in vitro
      selection from random rRNA fragments) that identifies protein binding sites
      within large RNAs. With this method, a small rRNA fragment derived from the 23S
      rRNA was isolated that binds simultaneously and independently the ribosomal
      proteins L4 and L24 from Escherichia coli. Until now the rRNA structure within
      the ternary complex L24-rRNA-L4 could not be studied due to the lack of an
      appropriate experimental strategy. Here we tackle the issue by separating the
      various complexes via native gel-electrophoresis and analyzing the rRNA structure
      by in-gel iodine cleavage of phosphorothioated RNA. The results demonstrate that
      during the transition from either the L4 or L24 binary complex to the ternary
      complex the structure of the rRNA fragment changes significantly. The identified
      protein binding sites are in excellent agreement with the recently reported
      crystal structure of the 50S subunit. Because both proteins play a prominent role
      in early assembly of the large subunit, the results suggest that the identified
      rRNA fragment is a key element for the folding of the 23S RNA during early
      assembly. The introduced in-gel cleavage method should be useful when an RNA
      structure within mixed populations of different but related complexes should be
      studied.

PMID- 11345439
TI  - A selection system for identifying accessible sites in target RNAs.
AB  - Although ribozymes offer tremendous potential for posttranscriptionally
      controlling expression of targeted genes, their utility is often limited by the
      accessibility of the targeted regions within the RNA transcripts. Here we
      describe a method that identifies RNA regions that are accessible to
      oligonucleotides. Based on this selection protocol, we show that construction of
      hammerhead ribozymes targeted to the identified regions results in catalytic
      activities that are consistently and substantially greater than those of
      ribozymes designed on the basis of computer modeling. Identification of
      accessible sites should also be widely applicable to design of antisense
      oligonucleotides and DNAzymes.

PMID- 11345440
TI  - Evaluation of methylphosphonates as analogs for detecting phosphate contacts in
      RNA-protein complexes.
AB  - The well-studied interaction between the MS2 coat protein and its cognate hairpin
      was used to test the utility of the methylphosphonate linkage as a phosphate
      analog. A nitrocellulose filter binding assay was used to measure the change in
      binding affinity upon introduction of a single methylphosphonate stereoisomer at
      13 different positions in the RNA hairpin. Comparing these data to the available
      crystal structure of the complex shows that all phosphates that are in proximity
      to the protein show a weaker binding affinity when substituted with a
      phosphorothioate and control positions show no change. However, in two cases, a
      methylphosphonate isomer either increased or decreased the binding affinity where
      no interaction can be detected in the crystal structure. It is possible that
      methylphosphonate substitutions at these positions affect the structure or
      flexibility of the hairpin. The utility of the methylphosphonate substitution is
      compared to phosphate ethylation and phosphorothioate substitution experiments
      previously performed on the same system.

PMID- 11345441
TI  - Streptavidin aptamers: affinity tags for the study of RNAs and
      ribonucleoproteins.
AB  - RNA affinity tags would be very useful for the study of RNAs and
      ribonucleoproteins (RNPs) as a means for rapid detection, immobilization, and
      purification. To develop a new affinity tag, streptavidin-binding RNA ligands,
      termed "aptamers," were identified from a random RNA library using in vitro
      selection. Individual aptamers were classified into two groups based on common
      sequences, and representative members of the groups had sufficiently low
      dissociation constants to suggest they would be useful affinity tools. Binding of
      the aptamers to streptavidin was blocked by presaturation of the streptavidin
      with biotin, and biotin could be used to dissociate RNA/streptavidin complexes.
      To investigate the practicality of using the aptamer as an affinity tag, one of
      the higher affinity aptamers was inserted into RPR1 RNA, the large RNA subunit of
      RNase P. The aptamer-tagged RNase P could be specifically isolated using
      commercially available streptavidin-agarose and recovered in a catalytically
      active form when biotin was used as an eluting agent under mild conditions. The
      aptamer tag was also used to demonstrate that RNase P exists in a monomeric form,
      and is not tightly associated with RNase MRP, a closely related ribonucleoprotein
      enzyme. These results show that the streptavidin aptamers are potentially
      powerful tools for the study of RNAs or RNPs.

PMID- 11345442
TI  - Theoretical framework for the distribution of trace metals among the
      operationally defined speciation phases of a sediment.
AB  - The use of a model based on Langmuir's isotherm to evaluate the metal associated
      with separate geochemical phases of a sediment is proposed and its validity
      tested with sediments of certified composition. The model takes into account a
      standard procedure for a certified reference material (CRM601), which defines,
      experimentally, a set of sequential extractions that divide the sediment into
      four operational fractions. The derived equations allow the treatment of data
      from sediment of Flumendosa Lake, Italy, and certified material CRM601 and also
      allow the computation of corrected concentrations, i.e., the metal affinities for
      each fraction. Experimental values for Ni show its low sensitivity and an equal
      distribution among different phases, which suggests a similar adsorption
      mechanism in all cases. In the case of Cd, the corrected concentration in the
      Fe/Mn oxide phase is nine times higher than for the residual fraction. For
      sediment of the Besos River, Spain, results show the percentage distribution of
      Ni over different fractions. Affinity values for Ni on a Flumendosa Lake sediment
      have also been calculated. The present model is simple to apply and shows
      satisfactory agreement with experimental data.

PMID- 11345443
TI  - Mineralization of organic contaminants in sludge-soil mixtures.
AB  - The mineralization of 14C-labeled linear alkylbenzene sulfonate (LAS),
      nonylphenol (NP), nonylphenol-di-ethoxylate (NP2EO), di-(2-ethylhexyl)phthalate
      (DEHP), pyrene, and 1,4-dichlorobenzene (DCB) was investigated in different
      sludge-soil mixtures and soils. Under aerobic conditions, the mineralization of
      LAS, NP, and NP2EO was between 50 and 81% of the added amounts after two months,
      while DEHP and pyrene were mineralized more slowly. The mineralization of the
      model chemicals was indirectly affected by the amount of sludge in the test
      mixtures. A higher content of sludge in the mixtures reduced the overall
      concentration of oxygen, which resulted in a decrease of the mineralization of
      several of the model chemicals. In sludge-soil mixtures with predominantly
      anaerobic conditions, the mineralization was slower for all of the chemicals with
      the exception of DEHP and DCB. The mineralization of DCB was enhanced in mixtures
      with a high sludge content. No pronounced difference in the mineralization of the
      model chemicals (except DEHP) was observed when the sludge was mixed with three
      different agricultural soils.

PMID- 11345444
TI  - A simple Tenax extraction method to determine the availability of sediment-sorbed
      organic compounds.
AB  - A simple method to determine the availability of sediment-sorbed organic
      contaminants was developed and validated. For 10 polycyclic aromatic
      hydrocarbons, 4 polychlorinated biphenyls, and 9 chlorobenzenes in 6 sediments,
      we measured the fraction extracted by Tenax in 6 and 30 h. These fractions were
      compared with the rapidly desorbing fractions determined by consecutive Tenax
      extraction. Extraction by Tenax for 30 h completely removed the rapidly desorbing
      fraction plus some part of the slowly desorbing fraction. The fraction removed
      after 30 h was about 1.4 times the rapidly desorbing fraction. The fraction
      extracted by Tenax after 6 h is about 0.5 times the rapidly desorbing fraction
      for chlorobenzenes (CBs)/polychlorinated biphenyls (PCBs) and polycyclic aromatic
      hydrocarbons (PAHs). The rapidly desorbing fraction probably represents the
      fraction of sorbed organic compound that poses actual risks for transport to
      (ground) water and determines the uptake by organisms and that can be microbially
      degraded. Extraction by Tenax for 6 h provides an easy way to address these
      issues more accurately than does the measurement of total concentrations.

PMID- 11345445
TI  - Impact of metal pools and soil properties on metal accumulation in Folsomia
      candida (Collembola).
AB  - Soil-dwelling organisms are exposed to metals in different ways. Evidence exists
      for predominant pore water uptake of metals by soft-bodied oligochaete species.
      In the present research, uptake kinetics of metals and the metalloid As by the
      semi-soft-bodied springtail Folsomia candida were studied, for which uptake via
      the pore water is less obvious. Springtails were exposed in 16 field soils and in
      metal-spiked artificial Organization for Economic Cooperation and Development
      (Paris, France) soil (OECD soil). Subsequently, accumulation parameters were
      statistically related to soil metal pools and soil properties. In Cd-spiked OECD
      soil, internal Cd levels were linearly related to external Cd concentrations,
      whereas the springtails maintained fixed internal levels of Cu and Zn regardless
      of spiked concentrations. In the field soils, all body concentrations of the
      elements As, Cr, and Ni were below detection limit. The essential metals Cu and
      Zn were presumably regulated, and no influence of soil characteristics could be
      demonstrated. For Cd and Pb, accumulation patterns were correlated mainly to
      solid-phase soil characteristics. The presence of these explanatory variables in
      the multiple correlations suggests that an uptake mechanism that is solely
      determined by pore water concentrations should not be taken as a universally
      applicable principle in risk assessments of metals for soil invertebrates.
      Cadmium in OECD soils was more available for uptake than in the field soils. The
      difference remained when extractability was taken into account. The results
      suggest that experiments in OECD soil cannot be used directly in risk assessment
      for nonessential metals (at least for F. candida), although a reduction of
      uncertainties in metal risk assessment can be reached by consistent use of body
      residues rather than external concentrations.

PMID- 11345446
TI  - Kinetics of polychlorinated biphenyl dechlorination and growth of dechlorinating
      microorganisms.
AB  - The present study has investigated a correlation between the kinetics of
      polychlorinated biphenyl (PCB) dechlorination and the growth of dechlorinating
      microbial populations. Microorganisms were eluted from Aroclor 1248-contaminated
      St. Lawrence River (NY, USA) sediments and inoculated into clean sediments spiked
      with Aroclor 1248 at 10 concentrations ranging from 0 to 3.12 micromol/g sediment
      (0-900 ppm). The time course of PCB dechlorination and population growth were
      concurrently determined by congener-specific analysis and the most probable
      number technique, respectively. The specific growth rate was a saturation
      function of PCB concentrations above the threshold concentration (0.14 micromol/g
      sediment, or 40 ppm), below which no dechlorination or growth of dechlorinations
      were observed. The maximum growth rate was 0.20/d with a half-saturation constant
      of 1.23 micromol/g sediment. The yield of dechlorinating microorganisms showed a
      peak at 0.70 micromol/g sediment (200 ppm), with a value of 10.3 x 10(12)
      cells/mol Cl removed, and decreased below and above this concentration. The
      dechlorination rate (micromol Cl removed/g sediment/d) was a linear function of
      Aroclor concentration. Both the log of this rate and the maximum level of
      dechlorination were significantly correlated with growth rate. The biomass
      normalized dechlorination rate (micromol Cl removed/g sediment/cell/d) was first
      order because of the exponential manner of the population growth. The first-order
      rate constant was a saturation function of Aroclor concentrations, with a maximum
      of 0.24/d (a half-life of 2.9 d) and a half-saturation constant of 1.18
      micromol/g sediment, which are similar to the constants for growth. These results
      indicate that the dechlorination rate is tightly linked to the population growth
      of dechlorinating microorganisms.

PMID- 11345447
TI  - Occurrence and potential adverse effects of semivolatile organic compounds in
      streambed sediment, United States, 1992-1995.
AB  - The occurrence and potential adverse effects of select semivolatile organic
      compounds (SVOCs) in streambed sediment were assessed at 536 sites in 20 major
      river basins across the United States from 1992 to 1995. Fifty-six SVOCs were
      detected at one or more sites, and one or more SVOCs were detected at 71% of
      sites. The northeastern and Great Lakes regions and large metropolitan areas have
      the highest SVOC concentrations. Polycyclic aromatic hydrocarbons (PAHs) were
      detected most frequently and at the highest concentrations. Concentrations of
      PAHs and phthalates were about 10 times higher at sites influenced by urban
      activities than at sites in other land-use areas. Semivolatile organic compounds
      were significantly (alpha = 0.05) correlated with land use and population
      density, and PAHs also correlated with physical/chemical properties. On the basis
      of sediment-quality guidelines, adverse effects are probable at 7.5% and possible
      at 16.2% of the sites. Most of the potential for adverse effects is due to PAHs.
      The median percentage of urban land use was 8% at sites with possible adverse
      effects and 16% at sites with probable adverse effects. Urbanization profoundly
      affects sediment quality, even though it comprised a small percentage of most
      drainage basins.

PMID- 11345448
TI  - Polychaete indicator species as a source of natural halogenated organic compounds
      in marine sediments.
AB  - Studies of pollutant impact on the marine environment assume that organic
      contaminants are anthropogenic in origin. However, many common polychaete worms
      and sediments contain readily detectable concentrations of brominated natural
      products that are often analogues of chlorinated anthropogenic contaminants. Both
      polychaetes and sediments are used extensively in environmental toxicology and
      monitoring, and the extent to which natural halometabolites may confound these
      studies is unknown. To characterize further the relationship among infauna,
      indicator species, and sedimentary halogenated organics, we examined sediments
      and infauna from a pristine habitat and animals maintained under laboratory
      culture for haloorganics using gas chromatography/mass spectrometry. Natural
      haloorganics are a consistent feature of pristine marine soft-bottom habitats,
      and their spatial and temporal variation correlates with the abundance of infauna
      that produce these metabolites. Abundant organohalogens are also present in the
      widespread polychaete indicator species Capitella sp. I and Streblospio benedicti
      but absent from the marine invertebrate toxicology model Neanthes
      arenaceodentata. Studies from the individual to the community level within the
      fields of ecology, toxicology, and environmental chemistry could be readily
      confounded by failing to consider these novel animal and habitat characteristics.

PMID- 11345449
TI  - Mobility and bioavailability of trace metals in sulfidic coastal sediments.
AB  - High concentrations of Hg, Cd, Pb, Cu, and Zn were found in the euxinic sediment
      of the inner archipelago of Stockholm. In the sulfide-rich sediment, they are
      precipitated as metal sulfides with low dissolving capacity and bioavailability.
      In two experiments, the significance of acid-volatile sulfide (AVS) and dissolved
      sulfides for mobility, bioavailability, and toxicity of metals were studied by
      oxygenation of intact sediment cores. Influence of bioturbating deposit-feeding
      amphipods, that is, Monoporeia affinis, was examined on studied sediment
      processes. Results showed a low mobility of most metals except Cd and Zn.
      Bioturbation did not enhance mobility. Cd and Zn, released from the sediment,
      were not bioaccumulated in amphipods. In contrast, the less mobile metals Hg and
      Pb were bioaccumulated. A low toxicity of contaminated sediments, in terms of
      mortality and embryonic malformations of amphipods, was recorded. Results
      indicate that Cd, Zn, and Cu are comparatively unavailable after oxygenation of
      the metal sulfides. Similar results were recorded in contaminated sediments
      differing in redox potential, AVS, dissolved sulfides, and organic contents,
      suggesting that other metal ligands, in addition to AVS, are important for metal
      bioavailability and toxicity in anoxic and suboxic environments.

PMID- 11345450
TI  - Runoff simulation with particle-bound fenvalerate in multispecies stream
      microcosms: importance of biological interactions.
AB  - Multispecies stream microcosms were used to test the toxicity of the pyrethroid
      fenvalerate (FV) associated with suspended particles in order to simulate a
      typical runoff exposure scenario. Stream microcosms were exposed for 1 h in
      triplicate to 0.0, 13.6, 136, or 1,365 microg/kg FV and effects were monitored
      for 93 d. Experimental design allowed for detection of interspecific effects on
      the emergence and thus survival of the caddisfly species Limnephilus lunatus
      Curtis and of intraspecific effects on the spatial distribution of adult and
      juvenile Gammarus pulex L. (Amphipoda). Exposure at 136- and 1,365 microg/kg
      resulted in a significant acute increase in drift. Survival of L. lunatus was
      significantly reduced in the 1,365-microg/kg treatment during single-species
      exposures. When other species were present, survival of L. lunatus was
      significantly reduced at 136 microg/kg. A similar increase in test system
      susceptibility was observed in relation to the spatial distribution of G. pulex.
      Juvenile individuals avoided areas with high numbers of adult amphipods, which
      may prey on the juveniles. This avoidance was significant in the control and the
      13.6-microg/kg treatment but did not occur at higher levels of exposure. This
      study highlights the ecotoxicological importance of field-relevant levels of
      particle-associated hydrophobic chemicals that transiently increase during runoff
      events. Interspecific and intraspecific interactions can alter the test results;
      i.e., significant lethal and sublethal effects are measurable at FV levels
      approximately an order of magnitude lower than when biological interactions are
      excluded.

PMID- 11345451
TI  - Toxicokinetics and toxicity of zinc under time-varying exposure in the guppy
      (Poecilia reticulata).
AB  - Levels of toxic substances released into the environment are often highly
      variable and fluctuate over time. The present study deals with a simple type of
      time-variable exposure, diluted pulse. We determined toxicokinetic parameters of
      zinc in guppy fish (Poecilia reticulata) and evaluated the applicability of a
      toxicokinetics-based survival model developed earlier. In the toxicokinetics
      experiment, zinc was rapidly taken up and released again; the half-life in fish
      was only 1.5 d. In the toxicity experiments with diluted-pulse exposure, survival
      leveled off to a baseline level, which in accordance with the model is explained
      by the dilution of zinc. The model fitted reasonably well for the lower initial
      concentrations but tended to overestimate survival rates at the higher
      concentrations. Toxicokinetic parameters estimated from changes in survival were
      close to values estimated from measured zinc concentrations in water. Elimination
      rates during pulse exposure varied from 0.434 to 0.488 d(-1) and corresponded
      very well to the elimination rate during constant exposure (0.463 d(-1)).
      Ultimate LC50 values were estimated as 6.40 and 9.10 mg/L. These results suggest
      that toxicity experiments with a simple, time-varying exposure can be used as an
      alternative to conventional, constant-exposure experiments. Toxicokinetic
      parameters and toxicological endpoints can still be estimated in static bioassays
      with decreasing exposure if the concentration in the medium is measured. At the
      same time, diluted-pulse experiments may simulate exposure from discharges in the
      field better than constant-exposure experiments.

PMID- 11345452
TI  - Effects of atrazine on embryos, larvae, and adults of anuran amphibians.
AB  - We examined the effects of atrazine (0-20 mg/L) on embryos, larvae, and adult
      anuran amphibian species in the laboratory. Atrazine treatments did not affect
      hatchability of embryos or 96-h posthatch mortality of larvae of Rana pipiens,
      Rana sylvatica, or Bufo americanus. Furthermore, atrazine had no effect on
      swimming speed (measured for R. pipiens only). However, there was a dose
      dependent increase in deformed larvae of all three species with increasing
      atrazine concentration. In adult R. pipiens, atrazine increased buccal and
      thoracic ventilation, indicating respiratory distress. However, because atrazine
      had no affect on hemoglobin, this respiratory distress was probably not
      indicative of reduced oxygen-carrying capacity of the blood. Frogs exposed to the
      highest atrazine concentration stopped eating immediately after treatment began
      and did not eat during the 14-d experiment. However, no decreases in mass were
      measured even for frogs that were not eating, probably because of compensatory
      fluid gain from edema. Atrazine concentrations found to be deleterious to
      amphibian embryos and adults are considerably higher than concentrations
      currently found in surface waters in North America. Therefore, direct toxicity of
      atrazine is probably not a significant factor in recent amphibian declines.

PMID- 11345453
TI  - Reproduction success of American kestrels exposed to dietary polychlorinated
      biphenyls.
AB  - While reproduction of wild birds is adversely affected by multiple environmental
      contaminants, we determined that polychlorinated biphenyls (PCBs) alone alter
      reproduction. Captive American kestrels (Falco sparverius), fed PCB-spiked
      (Aroclor 1248:1254:1260) food (7 mg/kg body weight/d) prior to and during the
      first breeding season only (100 d) laid eggs with environmentally relevant levels
      of total PCBs (34.0 microg/g whole egg wet wt vs 0 microg/g for controls).
      Reproduction changed during, not after, PCB exposure in this two-year study. The
      PCB-exposed pairs laid smaller clutches later in the season and laid more totally
      infertile clutches. Hatching success was reduced in PCB-exposed pairs, and 50% of
      PCB nestlings died within 3 d of hatching. Nearly 60% of PCB-exposed pairs with
      hatchlings failed to produce fledglings. Higher levels of total PCB residues and
      congeners were associated with later clutch initiation and fewer fertile eggs,
      hatchlings, and fledglings. We suggest that nonpersistent PCB congeners have a
      greater influence on reproduction than do persistent congeners.

PMID- 11345454
TI  - Effect of mercury and Gpi-2 genotype on standard metabolic rate of eastern
      mosquitofish (Gambusia holbrooki).
AB  - Previous studies demonstrated differential mortality among mosquitofish of
      different Gpi-2 genotypes during acute mercury and arsenate exposures. Mercury
      exposed mosquitofish also had Gpi-2 genotype-specific differences in glycolytic
      and Krebs cycle metabolite pools. The mortality and metabolite data suggested
      that mosquitofish bearing specific Gpi-2 genotypes might differ in metabolic
      efficiency, with less efficient Gpi-2 genotypes having higher standard metabolic
      rates (SMRs) and shorter times to death during acute mercury exposure. Effect of
      Gpi-2 genotype on SMR was assessed with a factorial arrangement of six Gpi-2
      genotypes and two exposure sequences (Control - Control; Control - 100 microg/L
      Hg). The SMRs were estimated by measuring oxygen consumption using an indirect,
      closed-circuit, computer-controlled respirometer. A 48-h exposure to 100 microg/L
      of mercury resulted in a 16.7% elevation of SMR above control levels (p = 0.001).
      The Gpi-2 genotype and the number of heterozygous loci per individual had no
      significant effect on SMR in mercury-exposed mosquitofish. The experimental
      results do not support the hypothesis that Gpi-2 genotype-specific differences in
      glycolytic and Krebs cycle metabolite pools and mortality in mosquitofish exposed
      to mercury are associated with differences in SMR.

PMID- 11345455
TI  - Effects of nonylphenol, bisphenol A, and their mixture on the viviparous
      swordtail fish (Xiphophorus helleri).
AB  - A number of fish species have been used for studies on endocrine disrupting
      chemicals (EDCs). However, despite the widespread use of oviparous fish,
      relatively little attention has been given to viviparous species. This study
      investigated the effects of EDCs in a viviparous fish and examined the possible
      usefulness of the fish as an alternative model for the studies on EDCs.
      Swordtails (Xiphophorus helleri) were exposed to nonylphenol (NP), bisphenol A
      (BPA), and their mixture. Both short-term (3-d) and relatively long-term (60-d)
      exposures were carried out using adult male and 30-d-old juvenile fish,
      respectively. Following the short-term exposure, both NP and BPA caused
      vitellogenin mRNA expression. Flow cytometric analysis and terminal
      deoxynucleotidyl transferase assay on the testes of treated fish indicated
      reproductive damage. Histopathological analysis found degenerative and necrotic
      cells in seminiferous tubules following the exposure to 100 ppb NP. The testes
      with lesions were also associated with highly suppressed spermatogenesis.
      Following the long-term exposure, both NP and BPA exposures significantly
      affected the growth of swordtails. In all cases, the results showed that the
      mixture was always more potent than a single chemical and that swordtail fish can
      be a useful model for the study of endocrine disruptors.

PMID- 11345456
TI  - Toxicity of boron to rainbow trout: a weight-of-the-evidence assessment.
AB  - From the large data set available on the toxicity of boron to aquatic organisms,
      the toxicity of boron to the early life stages of rainbow trout (Oncorhyncus
      mykiss) is the seminal issue relative to setting water quality criteria and
      effluent standards. Issues associated with the early life stage studies are the
      flat concentration-response curve, the low threshold of toxicity, and teratogenic
      effects observed. Recent laboratory and field studies offer new experimental data
      that make a weight-of-the-evidence assessment timely. In a re-examination of the
      effect of boron on the embryo-larval stage in rainbow trout and zebrafish,
      adverse effects due to boron deficiency are observed which decrease with
      increasing dose. It was found that low concentrations of boron stimulate
      embryonic growth in rainbow trout and increase the viability and survival of
      embryonic zebrafish. As boron concentration is further increased, the dose
      response curve becomes flat as homeostatic processes are active; this is followed
      at higher doses by a new adverse response that increases with increasing dose. As
      a result, the dose-response relationship is U shaped, consistent with the
      characteristic shape of an essential micronutrient. Thus, effects originally
      reported to be toxicity at low exposures rather may be due to boron deficiency.
      Water analyses in trout hatcheries and field studies in wild trout streams add
      additional information on the toxicity of boron to trout. Of particular note is a
      controlled field study carried out in the Firehole River in Yellowstone Park (WY,
      USA), where trout populations survive and reproduction successfully occurs in
      natural water containing boron concentrations up to and in some cases greater
      than 1.0 mg B/L. Teratogenic effects due to boron exposure were not observed in
      any of these more recent studies.

PMID- 11345457
TI  - Sea urchin fertilization assay: an evaluation of assumptions related to sample
      salinity adjustment and use of natural and synthetic marine waters for testing.
AB  - Most industrial effluents discharged into the marine coastal environment are
      freshwater in nature and therefore require manipulation prior to testing with
      marine organisms. The sea urchin fertilization test is a common marine bioassay
      used for routine environmental monitoring, investigative evaluations, and/or
      regulatory testing of effluents and sediment pore waters. The existing Canadian
      and U.S. Environmental Protection Agencies test procedures using sea urchin (and
      sand dollar) gametes allow for sample salinity adjustment using either brine or
      dry salts. Moreover, these procedures also allow for the use of either natural or
      synthetic marine water for culturing/holding test organisms and for full-scale
      testing. At present, it is unclear to what extent these variables affect test
      results for whole effluents. The test methods simply state that there are no data
      available and that the use of artificial dry sea salts should be considered
      provisional. We conducted a series of concurrent experiments aimed at comparing
      the two different treatments of sample salinity adjustment and the use of natural
      versus synthetic seawater in order to test these assumptions and evaluate effects
      on the estimated end points generated by the sea urchin fertilization sublethal
      toxicity test. Results from these experiments indicated that there is no
      significant difference in test end points when dry salts or brine are used for
      sample salinity adjustment. Similarly, results obtained from parallel (split
      sample) industrial effluent tests with natural and artificial seawater suggest
      that both dilution waters produce similar test results. However, data obtained
      from concurrent tests with the reference toxicant, copper sulfate, showed higher
      variability and greater sensitivity when using natural seawater as
      control/dilution water.

PMID- 11345458
TI  - Toxicity and bioaccumulation of DDT in freshwater amphipods in exposures to
      spiked sediments.
AB  - The amphipods Hyalella azteca and Diporeia spp. were exposed to sediments dosed
      with dichlorodiphenyltrichloroethane (DDT), and the toxicity and toxicokinetics
      were determined. The toxicity was evaluated with the equilibrium partitioning
      (EqP) and critical body residue approaches. The DDT in the sediments degraded
      during the equilibration period prior to organism exposure. Thus, the toxicity
      using EqP pore-water toxic units (TUs) was evaluated for DDT and its degradation
      product, dichlorodiphenyldichloroethane (DDD), as the ratio of the predicted
      interstitial water concentration divided by the water-only LC50 values. The sum
      of TUs (sum(TU)) was assumed to best represent the toxicity of the mixture. For
      H. azteca, the 10-d LC50 was 0.98 and 0.33 sum(TU) for two experiments. For
      Diporeia spp., no toxicity was found in the first experiment with up to 3 sum(TU)
      predicted in the interstitial water. However, in the second experiment, the 28-d
      LC50 was 0.67 sum(TU). These data suggest that the EqP approach approximately
      predicts the toxicity for the combination of DDT and DDD in sediment, provided a
      toxic unit approach is employed. The critical body residue approach also used TUs
      because DDT is biotransformed by H. azteca and because of the dual exposure to
      DDT and DDD. Because biotransformation was only determined in the second
      experiment, the critical body residue approach could only be evaluated for that
      case. The TUs were calculated as the ratio of the concentration in the live
      amphipods divided by the respective LR50 (residue concentration required to
      produce 50% mortality) values. The LR50 was 1.1 sum(TU) for H. azteca for the 10
      d exposure and 0.53 for Diporeia spp. after a 28-d exposure. Thus, this approach
      was also quite successful in predicting the toxicity. The accumulation and loss
      rates for H. azteca were much greater than for Diporeia spp. Thus, 10-d exposures
      represent steady-state conditions for H. azteca, while even at 28-d, the Diporeia
      spp. are not at steady state.

PMID- 11345459
TI  - Assessment of chloroaniline toxicity by the submitochondrial particle assay.
AB  - The effects on mitochondrial respiration of 15 chloroanilines were recorded by
      using the in vitro response of submitochondrial particles (SMP) from beef heart
      mitochondria. The bioassay procedure for SMP is based on the process of reverse
      electron transfer, which can be negatively affected by inhibitors of electron
      transport, by uncouplers, and by chemicals that impair membrane integrity. The
      EC50 values, determined for the tested chloroanilines, indicate a general
      tendency of increasing toxicity with increasing chlorine substitution. In order
      to validate the results obtained and to evaluate the capability of the SMP assay
      to reproduce the toxic effects of the examined compounds on different freshwater
      species, the EC50 values were compared with literature data from other biological
      assays regarding both in vitro systems and whole organisms. A good correlation
      was found in particular with two widely used testing systems, the Microtox and
      the Tetrahymena assays. In addition, quantitative structure-activity
      relationships (QSARs) were established between the EC50 values and various
      molecular descriptors for hydrophobic, steric, and electronic interactions. The
      results obtained were utilized to elucidate the mechanism of toxic action of
      chloroanilines, which are commonly reported to act by the polar narcosis mode of
      action. Moreover, they confirmed that the SMP assay can be a useful tool for
      studying the toxicity of chemicals that act nonspecifically by impairing membrane
      structure and functions.

PMID- 11345460
TI  - Assessment of sublethal endpoints for toxicity testing with the nematode
      Caenorhabditis elegans.
AB  - Toxicity tests in invertebrates often use sublethal endpoints, which may exhibit
      different sensitivity for various toxicants. Our objective was to characterize
      the sensitivity of movement, feeding, growth, and reproduction as endpoints for
      heavy metal toxicity testing with Caenorhabditis elegans. Growth and feeding were
      assessed in the same nematode samples used to assess movement and reproduction.
      Median effective concentrations (EC50s) for 24-h exposures to Pb, Cu, and Cd were
      determined for movement, feeding, and growth and a 72-h EC50 was derived for
      reproduction. The order of toxicity was Cu > Pb > Cd for each endpoint, including
      lethality and movement. There were no differences in sensitivity among endpoints
      for any metal. When exposed for 4 h at (sublethal) concentrations that were 14
      times the 24-h EC50 value, Pb and Cu reduced feeding to the same extent while
      movement was reduced significantly more by Pb than by Cu. Thus, a difference in
      sensitivity of endpoints was apparent at 4 h, which was not evident at 24 h.
      These observations suggest potentially different mechanisms of toxicity for 24-
      and 4-h tests.

PMID- 11345461
TI  - Toxicity-based criteria for the evaluation of textile wastewater treatment
      efficiency.
AB  - Brazilian textile mills import wastewater treatment technologies, performances of
      which are generally evaluated only on a physicochemical basis. Thus, a battery of
      bioassays was used to evaluate the performance of an ozonation system to treat
      textile effluents. Comparative toxicological profiles for bacteria (Vibrio
      fischeri), algae (Scenedesmus subspicatus), daphnia (Daphnia magna), fish
      (Poecilia reticulata), and plants (soybean--Glycine max, rice--Oryza sativa, and
      wheat--Triticum aestivum), as well as genotoxic effects (Vicia faba micronucleus
      assay), are presented for both raw and ozonated textile effluents. The relative
      sensitivity of bioassays (or end points) to textile effluents found in this study
      in decreasing order was plant enzymes > bacteria > algae daphnids approximately =
      plant biomass approximately = germination rate > fish. No significant genotoxic
      effect was found. We have concluded that ozonation was relatively effective in
      reducing toxicity of textile effluents. Bioassays used in this study proved to be
      sensitive and reliable tools for determining the toxicity of industrial
      effluents, and thus they can be used to evaluate emerging technology efficiency.

PMID- 11345462
TI  - Uptake, effects, and metabolism of cyanobacterial toxins in the emergent reed
      plant Phragmites australis (cav.) trin. ex steud.
AB  - The commonly occurring cyanobacterial toxin microcystin-LR (MC-LR) was rapidly
      taken up by the emergent reed plant Phragmites australis with clear distribution
      in the different cormus parts of the plant. Highest uptake was detected in the
      stem, followed by the rhizome. Enzyme extracts of the rhizome system, the stem,
      and the leaf revealed the presence of soluble glutathione S-transferases (sGST)
      measured with the model substrate 1-chloro-2,4-dinitrobenzene. A significant
      elevation of sGST activity in the rhizome and stem parts of P. australis was
      detected after a 24-h exposure to 0.5 microg/L MC-LR. Rhizome, stem, and leaf
      tissues were also able to conjugate several microcystin toxins. However, no
      conjugation, either chemical nor enzymatic, was detected using the related
      cyanobacterial toxin nodularin as substrate. Highest glutathione S-transferase
      activity for the toxin substrates was detected in the pkat/mg range in the stem
      of P. australis. For MC-LR, a complete metabolism from the formation of a
      glutathione conjugate to the degradation of a cysteine conjugate in all cormus
      parts of the plant is reported. The stepwise degradation of the MC-LR-glutathione
      conjugate to a gamma-glutamylcysteine and a cysteine conjugate was demonstrated
      by comparison with chemically formed reference compounds and by matrix-assisted
      laser desorption/ionization time-of-flight mass spectrometry. This is the first
      evidence for the uptake and metabolism of cyanobacterial toxins by an emergent
      aquatic macrophyte.

PMID- 11345463
TI  - Frequently co-occurring pesticides and volatile organic compounds in public
      supply and monitoring wells, southern New Jersey, USA.
AB  - One or more pesticides were detected with one or more volatile organic compounds
      (VOCs) in more than 95% of samples collected from 30 public supply and 95
      monitoring wells screened in the unconsolidated surficial aquifer system of
      southern New Jersey, USA. Overall, more than 140,000 and more than 3,000 unique
      combinations of pesticides with VOCs were detected in two or more samples from
      the supply and monitoring wells, respectively. More than 400 of these
      combinations were detected in 20% or more of the samples from the supply wells,
      whereas only 17 were detected in 20% or more of the samples from the monitoring
      wells. Although many constituent combinations detected in water from the supply
      and monitoring wells are similar, differences in constituent combinations also
      were found and can be attributed, in part, to differences in the characteristics
      of these two well types. The monitoring wells sampled during this study yield
      water that typically was recharged beneath a single land-use setting during a
      recent, discrete time interval and that flowed along relatively short paths to
      the wells. Public supply wells, in contrast, yield large volumes of water and
      typically have contributing areas that are orders of magnitude larger than those
      of the monitoring wells. These large contributing areas generally encompass
      multiple land uses; moreover, because flow paths that originate in these areas
      vary in length, these wells typically yield water that was recharged over a large
      temporal interval. Water withdrawn from public supply wells, therefore, contains
      a mixture of waters of different ages that were recharged beneath various land
      use settings. Because public supply wells intercept water flowing along longer
      paths with longer residence times and integrate waters from a larger source area
      than those associated with monitoring wells, they are more likely to yield water
      that contains constituents that were used in greater quantities in the past, that
      were introduced from point sources, and/or that are derived from the degradation
      of parent compounds along extended flow paths.

PMID- 11345465
TI  - Cadmium accumulation by invertebrates living at the sediment-water interface.
AB  - Benthic animals can take up trace metals both from the sediment compartment in
      which they burrow and from the water column compartment above their burrows (we
      define both compartments as containing water and particles). If criteria for the
      protection of benthic animals are based on metal concentrations in one of these
      two compartments, then it should first be demonstrated that the majority of the
      metal taken up by these animals comes from the given compartment. To determine
      whether benthic animals take up the majority of their cadmium (Cd) from the
      sediment compartment, we created a Cd gradient in lake sediment and compared Cd
      accumulation by the invertebrates colonizing these sediments with Cd
      concentrations in the sediment compartment. On the basis of this relationship and
      using a bioaccumulation model, we estimate that indigenous benthic invertebrates
      take up the majority of their Cd from the water column compartment. The results
      of our experiment are similar to those from a previous study conducted on a
      different benthic community in a larger lake. Taxa common to both lakes obtained
      similar proportions of their Cd from the water column compartment, suggesting
      that Cd accumulation by the same species will be constant across lakes of
      differing size and chemistry. Our results strengthen the argument that the
      protection of benthic communities from metal pollution should consider metal in
      both the water column and sediment compartments. In this regard, the AVS model,
      which considers only sedimentary metals, was more effective in predicting Cd
      concentrations in pore waters than those in most animal taxa. We suggest that
      measurements of vertical chemical heterogeneity in sediments and of animal
      behavior would aid in predicting the bioaccumulation and effects of sedimentary
      pollutants.

PMID- 11345464
TI  - Assessment of biological effects of chlorinated hydrocarbons in osprey chicks.
AB  - Osprey (Pandion haliaetus) eggs were collected during 1995 and 1996 at seven
      sites along the Fraser and Columbia River systems of British Columbia, Canada,
      and Washington and Oregon, USA. Fifty-four eggs were placed into a laboratory
      incubator. Thirty-eight of the hatched chicks were sacrificed within 24 h.
      Hatching success did not differ among sites and therefore between treatment and
      reference areas. Residual yolk sacs of eggs collected downstream of the large
      bleached-kraft pulp mill at Castlegar contained greater mean concentrations of
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, 2,930 ng/kg lipid) compared with
      reference sites such as the Nechako River, an upper tributary of the Fraser
      system (33.7 ng/kg). Total polychlorinated biphenyls (PCBs) in yolk sacs were
      also higher at Castlegar and in samples from the Columbia River downstream of
      Portland, Oregon, compared with those from the Nechako River. Concentrations of
      measured chemicals, including TCDD toxic equivalents (TEQs), total PCBs, p,p'
      dichlorodiphenylethylene (p,p'-DDE), and other organochlorines were not different
      in eggs that failed to hatch compared with calculated whole-egg values for
      hatched eggs. There were significant biochemical responses; a hepatic cytochrome
      P4501A (CYP1A) cross-reactive protein was detected in all samples tested and
      correlated positively with ethoxyresorufin o-deethylase (EROD) activity and yolk
      sac concentrations of TEQs and total PCBs. Tissue concentrations of vitamin A
      compounds varied among sites and correlated positively with yolk sac
      concentrations of TEQs and PCBs. Morphological, histological, and other
      physiological parameters, including chick growth, edema, deformities, and hepatic
      and renal porphyrin concentrations, neither varied among sites nor showed
      concentration-related effects.

PMID- 11345466
TI  - Chlorophyll fluorescence as a bioindicator of effects on growth in aquatic
      macrophytes from mixtures of polycyclic aromatic hydrocarbons.
AB  - Chlorophyll-a fluorescence induction is a rapid technique for measuring
      photosynthetic electron transport in plants. To assess chlorophyll-a fluorescence
      as a bioindicator of effects of polycyclic aromatic hydrocarbon mixtures,
      chlorophyll-a fluorescence parameters and plant growth responses to exposure to
      the wood preservative creosote were examined in the aquatic plants Lemna gibba
      and Myriophyllum spicatum. Exposure to creosote inhibited growth of L. gibba
      (EC50 = 7.2 mg/L total polycyclic aromatic hydrocarbons) and M. spicatum (EC50 =
      2.6 mg/L) despite differences in physiology. Creosote also diminished maximum
      PSII efficiency (Fv/Fm) (EC50 = 36 and 13 mg/L for L. gibba and M. spicatum) and
      the effective yield of photosystem II photochemistry (deltaF/Fm') (EC50 = 13 and
      15 mg/L for L. gibba and M. spicatum). The similarity between growth and
      chlorophyll-a fluorescence EC50s and slopes of the response curves suggests a
      close mechanistic link between these end points. The predictive power of
      chlorophyll-a fluorescence as a bioindicator of whole-organism effects applied to
      complex contaminant mixtures is discussed.

PMID- 11345467
TI  - Reevaluating the free-ion activity model of trace metal toxicity toward higher
      plants: experimental evidence with copper and zinc.
AB  - Across a diverse spectrum of organisms, the absorption and toxicity of trace
      elements are usually correlated with the activity of the free metal ion, but
      reported exceptions to this generalization are increasing. For the first time, we
      tested the validity of the free-ion activity model (FIAM) in the case of
      terrestrial plants and organic acids that may be abundant in the soil solution
      and rhizosphere. Short-term (48-h) root elongation of wheat (Triticum aestitvum
      L.) in a simple medium (2 mM CaCl2, pH 6.0) was used to probe the toxicity of Cu
      and Zn in the presence of malonate, malate, and citrate. Precautions were taken
      to prevent biodegradation of the organic acids, and its absence was confirmed by
      ion chromatography. Copper speciation was verified using a Cu-selective ion
      electrode, and published stability constants were modified to improve agreement
      between measured and calculated Cu2+ activities. With additions of both malonate
      and malate, Cu toxicity was alleviated but not to the extent predicted by the
      FIAM; the Cu-ligand complexes seemingly contributed to the toxicity. No such
      departures were observed with citrate and Cu nor with any of the three ligands in
      combination with Zn. Thus, exceptions to the FIAM occur with higher plants as
      well as with aquatic biota but do not seem to occur in a predictable or
      systematic fashion with respect to metal or organic acid under investigation.
      Several possible explanations for the observed departures from the FIAM are
      discussed, including the possibility of accidental cotransport of metal and
      ligand into the cytoplasm.

PMID- 11345468
TI  - Effects of copper on olfaction of Colorado pikeminnow.
AB  - Effects of copper on olfaction of Colorado pikeminnow (Ptychocheilus lucius) were
      investigated by exposing fish for 24 or 96 h, then evaluating olfactory ability
      using a behavioral assay and observing olfactory structures using scanning
      electron microscopy (SEM). The behavioral assay measured a response known as
      fright reaction. Failure of exposed fish to demonstrate a fright reaction in the
      presence of skin homogenate assumed to contain fright pheromone was considered
      evidence of copper-induced loss of olfactory ability. Regression analysis was
      used to describe the response of fish as a function of copper concentration at
      each exposure duration. Olfactory ability declined with increasing copper
      concentration. For copper concentrations less than 66 microg/L, olfaction was
      more sensitive to exposure at 24 h than at 96 h. This result suggests that
      physiological adaptation and recovery of sensory ability occurred despite
      continuous exposure in the 96-h treatment. Protective mechanisms induced by
      exposure may have reduced sensitivity to copper by 96 h. Systematic surveys using
      SEM to detect presence or absence of olfactory receptors confirmed results of
      behavioral assays. Copper concentrations in one river inhabited by Colorado
      pikeminnow were compared with effective concentrations estimated by regression.
      Comparisons suggest that ambient copper concentrations may occasionally inhibit
      olfaction of wild fish.

PMID- 11345469
TI  - Quantitative structure-activity relationships: comparative inhibition of nitrogen
      containing aromatics on germination of Cucumis sativus.
AB  - Comparative inhibition effect of selected nitrogen-containing aromatics on
      germination rate of Cucumis sativus was investigated, and quantitative structure
      activity relationships were developed and mechanistically interpreted. Energy of
      lowest unoccupied orbital was found to successfully model the toxicity of the
      test chemicals. It was discovered that inhibition of nitrogen-containing
      aromatics to germination of Cucumis sativus was caused mainly by their in vivo
      redox reaction.

PMID- 11345470
TI  - Correlation of Tetrahymena and Pimephales toxicity: evaluation of 100 additional
      compounds.
AB  - In the summary/recommendations for the Ecotoxicology Session of TestSmart--A
      Humane and Efficient Approach to Screening Information Data Sets (SIDS) Data
      Workshop, it was recommended that more population growth impairment data using
      Tetrahymena be generated and compared with available lethality data for the
      fathead minnow. To comply with this recommendation, 100 additional chemicals were
      tested in the ciliate assay. Toxicity values for the 96-h Pimephales promelas
      mortality assay (log[LC50(-1)]) and the 2-d Tetrahymena pyriformis growth assay
      (log[IGC50(-1)]) were compared. Each chemical was a priori assigned a mode of
      action. The majority of compounds were classified as either narcotics (n = 46) or
      direct-acting electro(nucleo)philes (n = 43), while 11 chemicals were listed as
      carboxylic acids, diesters, proelectrophiles, or weak acid respiratory
      uncouplers. Toxicities for narcotics showed an excellent relationship between
      endpoints with the coefficient of determination (r2) being 0.93. A weaker
      relationship, r2 = 0.78, was observed for the electro(nucleo)philes. The poorer
      fit for the covalent-reacting electro(nucleo)philes is attributed to differences
      in protocol, in particular, to test-medium composition and exposure scheme. Those
      chemicals whose potency is mediated by metabolism in fish (diesters and
      proelectrophiles) as well as the acids exhibited poor correlation between
      endpoints, with toxicity in the fish assay being greater than that predicted from
      the ciliate data. The regression analysis between endpoints, regardless of mode
      or mechanism of toxic action, yielded the model log(LC50(-1)) = 1.12(log[IGC50(
      1)]) + 0.46, with n = 92, r2 = 0.82, s (root of the mean square error) = 0.87, F
      = 399, and p > F = 0.0001. A result for the present investigation supports
      earlier findings that, with noted exceptions, there is a strong relationship
      between toxicity potency as quantified by P. promelas mortality and T. pyriformis
      growth impairment.

PMID- 11345471
TI  - Comparing representations of the environmental spatial scale of organic
      chemicals.
AB  - Long-range transport potential is one of the criteria proposed to identify
      chemicals as persistent organic pollutants. Here, different approaches to
      determine the spatial scale of an environmental area or region that can be
      impacted by an emitted chemical are investigated. A ranking of chemicals
      according to the spatial range R on a limited scale, as suggested by Scheringer,
      is equivalent to the characteristic travel distance L according to Bennett et al.
      on a linear, open scale. However, the methods are different with respect to the
      weighting of differences between the chemicals and according to their
      comparability with persistence. The characteristic travel distance L and the
      overall persistence are both plotted on open log-linear scales, whereas the
      spatial range R is represented on a limited scale. Various approaches of how to
      account for the mode of entry of chemicals are compared, and it is argued that
      relative measures are more appropriate to describe the long-range transport
      potential of chemicals than absolute numbers.

PMID- 11345472
TI  - Human toxicity potentials for life-cycle assessment and toxics release inventory
      risk screening.
AB  - The human toxicity potential (HTP), a calculated index that reflects the
      potential harm of a unit of chemical released into the environment, is based on
      both the inherent toxicity of a compound and its potential dose. It is used to
      weight emissions inventoried as part of a life-cycle assessment (LCA) or in the
      toxics release inventory (TRI) and to aggregate emissions in terms of a reference
      compound. Total emissions can be evaluated in terms of benzene equivalence
      (carcinogens) and toluene equivalents (noncarcinogens). The potential dose is
      calculated using a generic fate and exposure model, CalTOX, which determines the
      distribution of a chemical in a model environment and accounts for a number of
      exposure routes, including inhalation, ingestion of produce, fish, and meat, and
      dermal contact with water and soil. Toxicity is represented by the cancer potency
      q1* for carcinogens and the safe dose (RfD, RfC) for noncarcinogens. This article
      presents cancer and noncancer HTP values for air and surface-water emissions of
      330 compounds. This list covers 258 chemicals listed in U.S. Environmental
      Protection Agency TRI, or 79 weight-% of the TRI releases to air reported in
      1997.

PMID- 11345473
TI  - Attitudinal acceptance of intimate partner violence among U.S. adults.
AB  - Attitudinal acceptance of intimate partner violence (IPV) is an important
      correlate of violent behavior. This study examined acceptance of IPV using data
      collected from a nationally representative telephone survey of 5,238 adults.
      Multivariable logistic regression analyses were used to test for associations
      between sociodemographic characteristics, exposure to violence, question order,
      and acceptance of hitting a spouse or boyfriend/girlfriend under specific
      circumstances. Depending on the circumstance examined, acceptance of IPV was
      significantly higher among participants who were male and younger than 35; were
      non-White; were divorced, separated, or had never married; had not completed high
      school; had a low household income; or were victims of violence within the past
      12 months. Participants were more accepting of women hitting men; they also were
      consistently more likely to report tolerance of IPV if they were asked first
      about women hitting men rather than men hitting women. Reports of IPV tolerance
      need to be interpreted within the context of the survey. Efforts to change IPV
      attitudes can be tailored to specific IPV circumstances and subgroups, and these
      efforts should emphasize that the use of physical violence is unacceptable to
      both genders.

PMID- 11345474
TI  - Dropout and completion of treatment among spouse abusers.
AB  - This study examines a population of spouse abusers undertaking a treatment
      program. Its purpose was to identify the variables associated with dropout and
      completion of treatment and to build a predictive model. Data were collected on
      286 men who began group treatment in one of eight community programs in the
      province of Quebec, Canada. Results show that men who complete treatment are
      older, better educated and have better economic conditions than men who drop out.
      They also have a more stable family life, have been in a relationship for a
      longer period of time and have more children with their actual spouse. Men who
      completed treatment showed more commitment, better working capacities and a
      higher level of agreement with their therapists, thus developing a stronger
      therapeutic alliance. Support provided by people in the environment was
      significantly related to treatment completion. Social and judicial pressures were
      not related to completion.

PMID- 11345475
TI  - Perpetrators as victims: understanding violence by female street-walking
      prostitutes.
AB  - Little is known about the perpetration of violence by women who engage in street
      prostitution. While some researchers have examined the incidence of abuse among
      this population, the association between receipt of abuse and violence and later
      perpetration of violence is unclear. This study presents data from a recent
      evaluation of a case management program for street-walking prostitutes. A
      description of the program clients is provided, and factors that are associated
      with assaultive behavior against clients are examined. Bivariate analyses
      revealed statistically significant differences between assaultive and
      nonassaultive women with regard to history of psychiatric hospitalization,
      history of sexual abuse, history of physical abuse, history of emotional abuse,
      and whether they had been assaulted on the streets. However, logistic regression
      on variables related to abuse and violence indicates that controlling for other
      variables, the only statistically significant predictor of assaultive behavior
      was history of physical abuse. These results indicate the need for further
      research on this population as well as access to treatment for these women to
      address their own abuse and victimization.

PMID- 11345476
TI  - Family violence and substance use: the perceived effects of substance use within
      gay male relationships.
AB  - The purpose of this research endeavor is to examine the life situations of gay
      men where domestic violence was present. The current article expands on
      previously published works by examining respondents' perceptions of what role
      alcohol and other drug use plays in causing substance use-related domestic
      violence. Three different perceptions emerged from the data and are presented
      here. First, drugs and alcohol use was perceived to be causally related to the
      domestic violence our respondents endured. Second, our respondents believed
      substance abuse resulted from the violence--it was used as a coping mechanism.
      Finally, many respondents did not believe there was any association between
      substance abuse and violence. The need for further in-depth data related to the
      relationship between drugs, alcohol, and domestic violence is noted.

PMID- 11345477
TI  - Effects of alcoholic beverage, instigation, and inhibition on expectancies of
      aggressive behavior.
AB  - To investigate the role of alcohol expectancy, situational factors, and
      personality variables in predicting postdrinking aggression, two questionnaire
      studies were conducted. Subjects were randomly assigned to imagine themselves and
      their responses in a scenario situation, which was a combination of different
      beverages (soda vs. alcohol), instigation, and inhibition conditions. Both
      studies found significant 3-way interactions of personality aggression proneness
      (Buss-Durkee Hostility Inventory Assault scale) by beverage condition and by
      situational cue condition on subjects' reported likelihood of engaging in
      aggressive behavior. Expected aggression was strongly associated with greater
      aggression proneness in the nonalcoholic condition when there was a situational
      cue (low inhibition in Study 1, high instigation in Study 2) invoking aggression,
      but not when the situational cue was absent. This relationship between aggression
      proneness and expected aggression, however, was attenuated in the alcoholic drink
      conditions in both studies. In general, it was found that the effect of alcohol
      on expected aggression was minor relative to the large and significant effects of
      aggression proneness, instigation, and inhibition.

PMID- 11345478
TI  - The implementation of workplace violence policy in state government.
AB  - Workplace violence has received an increasing amount of attention in the last
      five years. While it is difficult to conclude that it is actually escalating, the
      numerous studies do provide numbers that lead one to believe that it is a serious
      problem. Although agencies and corporations are beginning to develop workplace
      violence policies, there is no published research that documents the results of
      the implementation of such policies. The current research examines North Carolina
      state employees' familiarity with their new workplace violence policy and
      reporting procedures, how uniformally the policy is being utilized, victims'
      perceptions of their agencies' responses to their own violent incidents, and
      their generalized perceptions of the agencies' intent to keep the workplace safe.

PMID- 11345479
TI  - Temperature, routine activities, and domestic violence: a reanalysis.
AB  - It was hypothesized that base rate differences in the number of complaints made
      during daylight and nighttime hours were responsible for a previously reported,
      nonlinear relationship between temperature and domestic violence. This hypothesis
      was tested by subjecting calls for service in 1987 and 1988 in Minneapolis, to
      moderator-variable regression analyses with controls for time of day, day of the
      week, season, and their interactions as well as linear trend, major holidays,
      public school closings, the first day of the month, and other weather variables.
      Temporal variables explained 75% of the variance in calls for service. As
      hypothesized, the base rate artifact was responsible for an apparent downturn in
      violence at high temperatures: Fewer complaints were received during afternoon
      hours, because they happen to be the warmest time of the day. The results were
      interpreted in terms of routine activity theory.

PMID- 11345480
TI  - 3,5-DHPG influences behavioral effects of baclofen in rats.
AB  - The role of 3,5-DHPG, an agonist of group I metabotropic glutamate receptors (I
      mGluRs) in certain behavioral effects of baclofen, an agonist of GABA-B receptor,
      was assessed. Baclofen, given intraperitoneally (ip) at the dose of 0.25 mg/kg,
      enhanced the number of crossings and bar approaches in the open field and was
      ineffective in the passive avoidance tests, and it prolonged time spent in closed
      arms and shortened time spent in open arms, reduced number of entries into open
      arms in the elevated "plus" maze, measuring anxiety. 3,5-DHPG given
      intracerebroventricularly (icv) alone at doses of 0.01, 0.1 and 1.0 nmole did not
      change locomotor activity in the open field test, except bar approaches: when 3,5
      DHPG was given at the dose of 0.01 nmole it enhanced the activity of rats. At
      doses of 0.01 and 1.0 nmole it improved, but at the dose of 0.1 nmole it
      significantly impaired retrieval in the passive avoidance situation. All used
      doses of 3,5-DHPG did not influence the time spent in closed or open arms and the
      number of entries into open or closed arms in the elevated "plus" maze. 3,5-DHPG,
      given at the doses of 0.01, 0.1 and 1.0 nmole 10 min after baclofen significantly
      changed the effect of baclofen decreasing crossings and rearings in the open
      field, while 3,5-DHPG used at the doses of 0.01 and 1.0 nmole in rats pretreated
      with baclofen reduced bar approaches. Rats which received baclofen and, 10 min
      later, 3,5-DHPG at doses of 0.1 and 1.0 nmole, showed significantly improved
      retrieval in the passive avoidance response. The effect of 3,5-DHPG and baclofen
      were changed, i.e. 3,5-DHPG and baclofen can cooperate in retrieval process.
      Coadministration of baclofen and 3,5-DHPG at the dose of 1.0 nmole reduced time
      spent in the open arms in comparison with baclofen, i.e. this dose of 3,5-DHPG
      changed the effect of baclofen evaluated in the "plus" maze. Summary, the
      activation of I mGluR by 3,5-DHPG modulates GABA-B neurotransmission stimulated
      by baclofen, which is reflected by changing behavioral activity of rats.

PMID- 11345481
TI  - Therapeutic drug monitoring in depression.
AB  - The difference between Therapeutic Drug Monitoring (TDM) and uncontrolled therapy
      consists in the fact that in TDM we can predict a certain scheme of treatment
      according to clinical and laboratory results. It is a method which serves to
      increase the efficacy and safety of pharmacotherapy in an individual patient.
      This paper presents the results of the treatment with tricyclic antidepressants
      based on the monitoring of serum drug level in 32 patients with indications for
      using pharmacogenetic as well as pharmacoelectroencephalographic tests. Clinical
      status of the patients was evaluated according to: Hamilton Depression Rating
      Scale (HDRS), Hamilton Anxiety Rating Scale (HARS), Clinical Global Impression
      Scale (CGIS), and TCA concentration in serum was determined using Fluorescence
      Polarization Immunoassay (FPIA). Hydroxylation phenotype was determined using
      debrisoquine as a model drug. EEG was recorded in four leads: F3-C3, F4-C4, P3
      O1, P4-O2. In the present study, we did not found any significant correlation
      between clinical status and serum TCAs concentrations measured by FPIA method.
      Efficacy of antidepressant treatment and stabilization of serum TCA
      concentrations depended largely upon the time course of the treatment.
      Debrisoquine phenotyping revealed the presence of one poor metabolizer (MR = 15)
      in the examined group of patients. A significant improvement in the clinical
      status of the patients, the stabilization of therapeutic drug concentrations, the
      appearance of antidepressive profiles in the pharmaco-EEG profile after 14 days
      of therapy, as well as the starting value determined by SERS were shown to be
      prognostic factors for the further antidepressant therapy.

PMID- 11345482
TI  - Anticonvulsant action of chlormethiazole is prevented by subconvulsive amounts of
      strychnine and aminophylline but not by bicuculline and picrotoxin.
AB  - The anticonvulsant action of chlormethiazole was evaluated with the use of
      subthreshold doses of convulsants affecting the purinergic, glycinergic and gamma
      aminobutyric acid (GABA)-mediated transmission, i.e. aminophylline, strychnine,
      bicuculline and picrotoxin in the model of generalized tonic-clonic convulsions.
      Chlormethiazole protected mice against maximal electroshock-induced seizures with
      an ED50 of 130.8 mg/kg. Aminophylline (100 mg/kg) and strychnine (0.4 mg/kg)
      reversed the protective action of chlormethiazole against electroconvulsions
      raising the ED50 values of this drug to 218.6 and 208.6 mg/kg, respectively. In
      contrast, GABA antagonists, bicuculline and picrotoxin, neither affected the
      protection provided by chlormethiazole nor did they alter the protective activity
      of valproate, phenobarbital, diphenylhydantoin and carbamazepine against
      electroconvulsions. Our results indicate that (a) the anticonvulsant activity of
      chlormethiazole might be related to its interaction with strychnine-sensitive
      glycinergic as well as purinergic neurotransmission, (b) purinergic and
      strychnine-sensitive glycinergic events contribute more prominently than
      GABAergic ones to the anticonvulsant activity of the drugs providing protection
      against maximal electroshock-induced convulsions.

PMID- 11345483
TI  - Effect of MK-801 on pilocarpine-evoked seizures in mice exposed to transient
      incomplete brain ischemia.
AB  - The aim of the study was to examine the role of NMDA receptors in the modulation
      of brain tolerance after transient cerebral ischemia. Adult mice were exposed for
      30 min to bilateral clamping of common carotid arteries (BCCA) under anaesthesia.
      The non-competitive NMDA antagonist, MK-801 was administered intraperitoneally
      (ip) in two experimental paradigms: a) acute: twice at 1.0 mg/kg; 1 h before the
      clamping of the vessels and 6 h after re-circulation; b) chronic at a dose of 0.1
      mg/kg, started 24 h after recirculation and continued once daily for 13 days with
      the last injection 24 h before the induction of convulsions. Seizures were evoked
      with pilocarpine (400 mg/kg, ip) 14 days after BCCA. It was found that transient
      incomplete brain ischemia induced protection against pilocarpine toxicity. The
      acute treatment with MK-801 did not diminish the anticonvulsant action of the
      procedure. In contrast, the chronic treatment with the drug led to a marked
      potentiation of the effect. In conclusion, it can be suggested that studied NMDA
      receptor antagonist used at relatively low dose may enhance the brain tolerance
      activated after a transient ischemic episode.

PMID- 11345484
TI  - Anticonvulsant activity of p-chlorophenyl substituted arylsemicarbazones--the
      role of primary terminal amino group.
AB  - A series of p-chlorophenyl substituted arylsemicarbazones were synthesized and
      evaluated for anticonvulsant activity. Most of the compounds provided significant
      protection against maximal electroshock-induced seizures (MES) at 100 mg/kg after
      0.5 h and at 300 mg/kg after 4 h in both MES and pentetrazole-induced (PTZ)
      seizures. In the strychnine-induced seizures (scSTY), the majority of the
      compounds showed protection at 30 mg/kg. The compound 2 was active in both MES
      and PTZ tests. The study has shown that the terminal primary amino group is not
      necessary for anticonvulsant activity.

PMID- 11345485
TI  - Effect of clofibrate on plasma lipid concentration and liver malic enzyme gene
      expression in rats with experimental chronic renal failure.
AB  - Fibrates have been used clinically to treat dyslipidemias, including chronic
      renal failure (CRF)-related hypertriacylgliceridemia. In addition to their
      effects on plasma triacylglycerol concentration, fibrates also induce
      hepatomegaly (due to peroxisome proliferation) and increase liver malic enzyme
      activity. Since most experiments regarding fibrates action have been performed on
      healthy animals, in this paper we compare the effect of clofibrate on: a) plasma
      lipid concentration; b) liver weight; c) liver malic enzyme gene expression
      (malic enzyme activity, malic enzyme protein level and malic enzyme mRNA
      abundance) in control (sham-operated) animals and rats with CRF. The data
      presented in this paper indicate that: a) the clofibrate treatment causes a
      decrease in triacylglycerol concentration both in the control and rats with CRF,
      however the effect of the drug was more pronounced in the latter; b)
      administration of clofibrate induces hepatomegaly both in the control and rats
      with CRF; c) the liver malic enzyme gene expression is similarly affected by
      clofibrate in the control and rats with CRF. It is concluded that the beneficial,
      therapeutic effect of clofibrate on plasma lipid concentration is more pronounced
      in rats with CRF, but the side effects (hepatomegaly and the increase in malic
      enzyme gene expression) of fibrates are essentially similar in the control and
      rats with CRF.

PMID- 11345486
TI  - Comparison of motor reactivity of the human colon cold-stored in different
      preservative solutions to carbachol and noradrenaline in vitro.
AB  - We have compared the reactivity to carbachol and noradrenaline of circular smooth
      muscle isolated from the human colon which was cold-stored at 4 degrees C in
      three different preservative solutions: Krebs bicarbonate solution (KBS),
      phosphate buffer solution (PBS) or minimum essential medium (MEM). Concentration
      dependent contractions in response to carbachol were reduced in terms of both
      their sensitivity (pEC50) and reactivity (Emax), depending on the period of cold
      storage. The reduction was more marked when the tissue was cold-stored in either
      MEM or KBS than in PBS. Similar reduction of the relaxation response to
      noradrenaline was also observed after cold storage. It is concluded that the cold
      storage of surgically resected human colon in PBS for two to three days best
      preserved smooth muscle functions for pharmacological examinations.

PMID- 11345487
TI  - Trace-level determination of nifedipine in human serum by reversed phase high
      performance liquid chromatography.
AB  - A rapid, simple, specific and sensitive high performance liquid chromatographic
      method has been developed for the determination of nifedipine (adalate) in human
      serum using diazepam (valium) as an internal standard (I.S.). The method utilized
      a 5 microm nonpolar C18 reversed phase Hypersil (ODS) column (250 x 3 mm i.d.).
      The mobile phase consisted of 60% v/v, acetonitrile in water, adjusted to pH 3.7
      with glacial acetic acid and ammonium acetate, and pumped at a flow rate of 2
      ml/min. The effluent was monitored by UV detection at 340 nm and a sensitivity
      fixed at 0.02 aufs. Each analysis required no longer than 4 min. The minimum
      detectable amount of nifedipine in serum was 3 ng/ml, and the mean absolute
      recovery was 93.5%. The within and between-day coefficients of variation at three
      different concentrations from 15-160 ng/ml ranged from 2.07 to 7.76%, and from
      3.15 to 7.98% respectively. Calibration graphs for 10 to 200 ng/ml were linear
      with a mean correlation coefficient, r (n = 36) of 0.9991. The method was
      validated for accuracy, sensitivity, selectivity and reproducibility and finally
      was utilized and proved to be suitable in a bioavailability study of two products
      of nifedipine following oral administration to healthy male subjects.

PMID- 11345488
TI  - Combined treatment with NMDA antagonist, CGP 37849, and sigma receptor agonists,
      SA4503 or DTG, decreases the neuroleptic-induced catalepsy in rats.
AB  - The obtained results indicate that joint administration of CGP 37849, a
      competitive NMDA receptor antagonist, and SA4503, a sigma1 (sigma1) receptor
      agonist or DTG, sigma 1/2 receptor agonist, evoked anticataleptic effect at doses
      which were ineffective when each of the compounds was given alone.

PMID- 11345489
TI  - Influence of new monoterpene homologues of GABA on the central nervous system
      activity in mice.
AB  - This behavioral study in mice showed that the monoterpene homologues of GABA (SL
      1, SL-2 and SL-3), characterized by low toxicity, induced an increase in
      spontaneous locomotor activity (SL-2 and SL-3). Moreover, SL-3 shortened
      hexobarbital-induced sleeping time, and SL-1 showed anticonvulsant activity in
      pentetrazole-induced seizures.

PMID- 11345490
TI  - Experimental peritonitis in anuran amphibians is not suppressed by morphine
      treatment.
AB  - Morphine-induced inhibition of peritoneal inflammation, consistently recorded in
      several murine strains and in fish (salmon and goldfish), was not observed in the
      investigated species of anuran amphibians (Rana temporaria, Rana esculenta and
      Bombina bombina).

PMID- 11345491
TI  - A quantitative model of work-related fatigue: empirical evaluations.
AB  - Systematic and quantitative management of work-related fatigue within workplaces
      has been a challenging task due to a lack of useful tools. A previous paper
      provided background and development of a work-related fatigue modelling approach.
      The current paper outlines model evaluations using sleep deprivation experiments
      and recommendations of work scheduling. Previous studies have reported cumulative
      effects of sleep restriction (4-5 h per night) on a number of measures. Model
      predictions were correlated against psychomotor vigilance task lapses (r = 0.92)
      and reaction time responses (slowest 10%, r = 0.91) as well as sleep latency (r =
      -0.97). Further correlations were performed on four measures from a 64 h
      continuous sleep deprivation study; that is objective vigilance (r = -0.75) as
      well as subjective performance (r = -0.75), sleepiness (r = 0.82) and tiredness
      (r = 0.79). Evaluation against current scheduling recommendations illustrated
      consistency with the literature with the exception that forward rotation did not
      provide benefits over backward rotation. The results indicate that model
      predictions correlate well across a range of objective and subjective measures.
      This relationship also appears to hold for cumulative and continuous sleep
      deprivation protocols. Future studies will also focus on field-based evaluation.

PMID- 11345492
TI  - The effect of overhead drilling position on shoulder moment and electromyography.
AB  - The effect of overhead drilling tasks on electromyographic (EMG) activity and
      shoulder joint moment was examined in this study. Twenty subjects simulated an
      overhead drilling task using a close, middle and far reach position while
      standing on either a lower or a higher step of a stepladder. Root mean square
      amplitude (AMP) of EMG activity from the dominant side anterior deltoid, biceps
      brachii and triceps brachii muscles was used to determine muscular load. Digital
      video was used to determine shoulder joint moment using 2-dimensional static link
      segment modelling in the sagittal plane. The results demonstrated that, compared
      to the far reach position, using the close reach position significantly decreased
      anterior deltoid AMP and biceps brachii AMP and moment, but increased triceps
      brachii AMP. Compared to the lower step, using the higher step significantly
      decreased anterior deltoid AMP and triceps AMP and moment, while increasing
      biceps AMP in the close position. There was no significant change noted in EMG
      median frequency indicating that fatigue was minimized. Moment increased
      monotonically with AMP. The findings indicated that workers performing overhead
      tasks should work close to their body in order to minimize shoulder forces. The
      implications of this recommendation are discussed.

PMID- 11345493
TI  - Tympanic temperature and heart rate changes in firefighters during treadmill runs
      performed with different fireproof jackets.
AB  - Six well-trained firefighters performed six treadmill runs at 70% of the velocity
      at VO2max (Maximal aerobic velocity MAV = 13.2+/-0.3 km h(-1)). A recovery time
      of 1 week was allowed between trials. The first session was performed by subjects
      wearing only shorts (i.e. no fire jacket, J0). A similar protocol was applied
      subsequently to test the physiological effects associated with the wearing of one
      of five different fire jackets: one leather (J1) and four textile-type jackets:
      VTN with membrane (J2), VTN without membrane (J3), Vidal with Kermel HTA (Haute
      Teneur en Aramide i.e. high density in Aramide) (J4); and Rolland with Kermel HTA
      (J5). All sessions were performed in a randomized order and in laboratory
      conditions. Exercise with the fireproof jackets resulted in higher tympanic
      temperature (Tty), heart rate (HR) and body mass loss (BML) changes compared to
      J0 (p<0.001). The magnitudes of these changes depended on the type of the jacket.
      Exercise in the leather jacket (J1) resulted in the highest Tty and HR, which
      differed significantly from values in all other conditions (p<0.001). The
      exercise-induced increases in Tty wearing jackets J3 and J5 were also
      significantly (p < 0.05) higher than those observed with jackets J2 and J4. In
      conclusion, textile jackets induced less HR and Tty stresses than the leather
      one. The magnitude of the physiological responses induced by textile jackets were
      correlated to jacket weight. J2 and J4 jackets were more effective in limiting
      hyperthermia and any potential detrimental effect on the exercise capacity.

PMID- 11345495
TI  - Characteristics of cursor trajectories controlled by the computer mouse.
AB  - An analysis of computer screen cursor trajectories can provide insights into the
      factors limiting efficient cursor positioning and can assist in the design of
      human-computer interfaces. Cursor locations as controlled by a Microsoft computer
      mouse with standard settings were therefore sampled at 5 ms intervals and
      kinematic analyses addressed the proportions of time spent in the initiation,
      accelerative and terminal guidance phases of cursor positioning. Twelve
      participants used a computer mouse to move a cursor over different distances (7.5
      cm, 15 cm) from a home location in the lower centre of the screen to targets of
      different diameters (8 mm, 16 mm), situated to the left, middle or right of the
      computer screen. Cursor trajectories were irregular, and participants regularly
      overshot their targets, spending 70% of movement duration in terminal guidance.
      Participants appeared to use the initial part of their movement to establish
      mappings between controller and display. Interventions should seek to reduce the
      terminal guidance phase of cursor positioning.

PMID- 11345494
TI  - Improving obstacle detection by redesign of walking canes for blind persons.
AB  - This paper describes an experiment in which the performance of cane walkers with
      the traditional straight long cane and a redesigned cane, the curved cane, was
      compared. The curved cane has a curve where the tip touches the ground.
      Participants were 18 experienced cane walkers who were totally blind. The aspects
      of cane walking that were investigated included obstacle detection, drop-off
      (slope) detection and walking speed. The performance with both canes was
      investigated in two different ways: (1) by means of constructed courses in which
      objective measures of cane walking were derived; and (2) by means of more
      qualitative measures based on the participants' experiences with the curved cane
      during a 3-week try-out period. Results showed that obstacle-detection was
      significantly better with the curved cane, whereas drop-off detection and walking
      speed were comparable for the two canes. The participants' experiences mirrored
      these results.

PMID- 11345496
TI  - Preventing falls from roofs: a critical review.
AB  - Work-related falls from roofs remain a significant problem for workers in the
      construction industry. Knowledge about the main causative or initiating factors
      leading to fall incidents is desperately needed for fall prevention intervention.
      From biomechanical and psychophysiological perspectives the majority of
      occupational falls, including falls from roofs, can be regarded as loss-of
      balance incidents. The primary objective of this paper is to summarize the
      current knowledge from multiple fields about factors that are related to the
      control of balance during roofing work. An extensive literature review identified
      a number of environmental, task-related and personal factors that degrade the
      control of balance and could be associated with the initiation of falls from
      roofs. These factors include visual exposure to elevation; unstable visual cues
      and inadequate visual information in the work environment; 'confined' and
      inclined support surfaces; unexpected changes in roof surface properties; load
      handling; physical exertion; fatigue; task complexity that diverts workers'
      attention; individual differences; work experience and training; and personal
      protective equipment. Current measures to reduce falls from roofs focus mainly on
      fall protection procedures, such as the use of covers, guardrails, safety nets,
      and personal fall-arrest systems, or the application of warning-line systems,
      safety monitoring systems, and fall protection plans. In many instances, these
      procedures are not practical for the industry and current regulations allow the
      use of alternative means of fall protection, such as slide guards. Future
      research on preventing falls from roofs should consider the main effects and
      interactions of the environmental, task-related and personal factors that affect
      the balance control of workers. Research-supported improvements in the visual and
      physical characteristics of the roof work environment, the construction materials
      and methods, and work procedures and practices may result in improved workers'
      balance control as well as overall safety performance, and would ultimately
      reduce incidents of falling from a roof.

PMID- 11345497
TI  - Combined effects of working environmental conditions in VDT work.
AB  - The combined effects of city noise and luminance of the computer display were
      evaluated from the changes in lymphocytes and mental activities of participants.
      Healthy male students were tested under the following four experimental
      conditions: (1) a calculating task on a video display terminal (VDT) with
      luminance of 90 cd m(-2) without city noise; (2) a calculating task on a VDT with
      luminance of 20 cd m(-2) without city noise; (3) a calculating task on a VDT with
      luminance of 90 cd m(-2) with city noise of 70 dB(A); and (4) a calculating task
      on a VDT with luminance of 20 cd m(-2) with city noise of 70 dB(A). A visual
      reaction test (VRT) was performed, and critical flicker fusion frequency (CFF),
      heart rate (HR), numbers of circulating white blood cells (WBCs), lymphocyte
      subsets and subjective symptoms of fatigue were measured (1) before; (2) just
      after; and (3) 30 min after each 60 min test. Subjective symptoms of fatigue
      significantly increased just after experiments conducted under the two noisy
      conditions. VRT and CFF showed significant changes in the case of the high
      luminance display with noise. WBCs and neutrophils showed significant increases
      in the two quiet conditions. These results suggested that high luminance with
      noise had the most effect on subjective fatigue and mental activities.

PMID- 11345498
TI  - A brief history of the Japan Society for Cell Biology.
AB  - The Japan Society for Cell Biology (JSCB) was first founded in 1950 as the Japan
      Society for Cellular Chemistry under the vigorous leadership of Seizo Katsunuma,
      in collaboration with Shigeyasu Amano and Satimaru Seno. The Society was
      provisionally named as above simply because cell biology had not yet been coined
      at that time in Japan, although in prospect and reality the Society was in fact
      for the purpose of pursuing cell biology. Later in 1964, the Society was properly
      renamed as the Japan Society for Cell Biology. After this renaming, the JSCB made
      great efforts to adapt itself to the rapid progress being made in cell biology.
      For this purpose the Society's constitution was created in 1966 and revised in
      1969. According to the revised constitution, the President, Executive Committee
      and Councils were to be determined by ballot vote. The style of the annual
      meetings was gradually modified to incorporate general oral and poster
      presentations in addition to Symposia (1969-1974). The publication of annual
      periodicals in Japanese called Symposia of the Japan Society for Cellular
      Chemistry (1951-1967) and later Symposia of the Japan Society for Cell Biology
      (1968-1974) was replaced by a new international journal called Cell Structure and
      Function initiated in 1975. This reformation made it possible for the Society to
      participate in the Science Council of Japan in 1975 and finally in 1993 to
      acquire its own study section of Cell Biology with grants-in-aid from the
      Ministry of Education and Science, Japan. The JSCB hosted the 3rd International
      Congress on Cell Biology (ICCB) in 1984 and the 3rd Asian-Pacific Organization
      for Cell Biology (APOCB) Congress in 1998, thus contributing to the international
      advancement of cell biology. Now the membership of JSCB stands at approximately
      1,800 and the number of presentations per meeting is 300 to 400 annually.
      Although a good number of interesting and important findings in cell biology have
      been reported from Japan, the general academic activity of the JSCB is far less
      than one might expect. This is simply due the fact that academic activity in the
      field of cell biology in Japan is divided among several other related societies
      such as the Japan Society for Molecular Biology and the Japan Society for
      Developmental Biology, among others.

PMID- 11345499
TI  - Is PECAM-1 a mechanoresponsive molecule?
AB  - Endothelial cells are capable of responding to fluid shear stress, but the
      molecular mechanism for this biological response remains largely unknown. Our
      studies indicate that the cell-cell adhesion site is a possible site of flow
      sensing. PECAM-1, a cell adhesion molecule localized to the interendothelial cell
      adhesion site, is tyrosine-phosphorylated when endothelial cells are exposed to
      physiological levels of fluid shear stress. This PE-CAM-1 phosphorylation
      initiates a signaling cascade leading to ERK activation. Here we review what is
      known about PECAM-1 tyrosine phosphorylation and suggest a possible role of PECAM
      1 in mechanosensing by endothelial cells.

PMID- 11345500
TI  - Role of ETS family transcription factors in vascular development and
      angiogenesis.
AB  - The ETS family of transcription factors is defined by a conserved DNA-binding ETS
      domain that forms a winged helix-turn-helix structural motif. This family of
      transcription factors is involved in a diverse array of biological functions
      including cellular growth and differentiation, as well as organ development.
      Among the members of this family, ETS-1, ERG, Fli-1, TEL, and NERF-2 are
      expressed in endothelial cells and their progenitors. This review will summarize
      the role of ETS family transcription factors in vascular development and
      angiogenesis.

PMID- 11345501
TI  - Structure and function of VEGF/VEGF-receptor system involved in angiogenesis.
AB  - Angiogenesis is an essential biological process not only in embryogenesis but
      also in the progression of a variety of major diseases such as cancer, diabetes
      and inflammation. Vascular endothelial growth factor (VEGF) family and its
      receptor system has been shown to be the fundamental regulator in the cell
      signaling of angiogenesis. Other systems, Angiopoietin-Tie and EphrinB2-Eph4B
      etc. are also involved in and cooperate with VEGF system to establish the dynamic
      blood vessel structures. VEGF receptor belongs to PDGF receptor super-gene
      family, and carries seven Ig-domains in the extracellular region and a tyrosine
      kinase domain in the intracellular region. Three members of VEGF receptor family,
      Flt-1, KDR/Flk-1 and Flt-4, have unique characteristics in terms of the signal
      transduction, and regulate angiogenesis, lymphangiongenesis and vascular
      permeability. Further studies on VEGF-VEGF receptor system may significantly
      facilitate our understanding on the physiological as well as pathological
      vascular systems in the body and the development of new strategies to control and
      suppress the major diseases in humans.

PMID- 11345502
TI  - Characterization of heterokaryons between skeletal myoblasts and somatic cells
      formed by fusion with HVJ (Sendai virus); effects on myogenic differentiation.
AB  - In skeletal myogenic differentiation, myoblasts fuse with myogenic cells
      spontaneously, but do not fuse with non-myogenic cells either in vivo or in
      vitro, suggesting that the fusion of myoblasts with non-myogenic cells is
      unsuitable for differentiation. To understand the inevitability of the fusion
      among myoblasts, we prepared heterokaryons in crosses between quail myoblasts
      transformed with a temperature-sensitive mutant of Rous sarcoma virus (QM-RSV
      cells) and rodent non-myogenic cells, such as tumor cells, fibroblasts, or
      neurogenic cells by HVJ (Sendai virus) and examined how myogenic differentiation
      was influenced in the prepared heterokaryons, focusing on myogenin expression and
      myofibril formation as markers of differentiation. When presumptive QM-RSV cells
      were fused with non-myogenic cells by HVJ and induced to differentiate, both
      myogenin expression and myofibril formation were suppressed. When myotubes of QM
      RSV cells that had already expressed myogenin and formed myofibrils were fused
      with non-myogenic cells, both myogenin and myofibrils disappeared. Especially,
      fibrous structures of myofibrils were significantly lost and dots or aggregations
      of F-actin were formed within 24 hr after formation of heterokaryons. However,
      the fusion of presumptive or differentiated QM-RSV cells with rodent myoblasts
      did not disturb myogenin expression or myofibril formation. These results suggest
      that mutual fusion of myoblasts is indispensable for normal myogenic
      differentiation irrespective of the species, and that some factors inhibiting
      myogenic differentiation exist in the cytoplasm of non-myogenic cells, but not in
      myoblasts.

PMID- 11345503
TI  - Detection and localization of a Ca2+-ATPase activity in Toxoplasma gondii.
AB  - Toxoplasma gondii, the agent causing toxoplasmosis, is an obligate intracellular
      protozoan parasite. A calcium signal appears to be essential for intracellular
      transduction during the active process of host cell invasion. We have looked for
      a Ca2+-transport ATPase in tachyzoites and found Ca2+-ATPase activity (11-22 nmol
      Pi liberated/mg protein/min) in the tachyzoite membrane fraction. This ATP
      dependent activity was stimulated by Ca2+ and Mg2+ ions and by calmodulin, and
      was inhibited by pump inhibitors (sodium orthovanadate or thapsigargin). We used
      cytochemistry and X-ray microanalysis of cerium phosphate precipitates and
      immunolabelling to find the Ca2+, Mg2+-ATPase. It was located mainly in the
      membrane complex, the conoid, nucleus, secretory organelles (rhoptries, dense
      granules) and in vesicles with a high calcium concentration. Thus, Toxoplasma
      gondii possesses Ca2+-pump ATPase (Ca2+, Mg2+-ATPase) as do eukaryotic cells.

PMID- 11345504
TI  - Current understanding of the biology of vascular endothelium.

PMID- 11345505
TI  - Strategies for success: working with children with developmental coordination
      disorder.

PMID- 11345506
TI  - Cognitive orientation to daily occupational performance (CO-OP): part III--the
      protocol in brief.
AB  - Parts I and II of this series introduced the Cognitive Orientation to daily
      Occupational Performance (CO-OP), a new approach to intervention that is based on
      the premise that cognition plays an important role in the acquisition of
      occupational skills and the development of occupational competency. Developed for
      use with children who have occupational performance deficits, CO-OP is an
      individualized, client-centred approach focused on strategy-based skill
      acquisition. This third paper in this series presents a brief description of the
      actual CO-OP protocol including its objectives, prerequisites and key features.

PMID- 11345507
TI  - Cognitive strategies and motor performance in children with developmental
      coordination disorder.
AB  - Recently, researchers in occupational therapy have investigated the use of a
      cognitive or "top down" approach to improving the occupational performance of
      children with developmental coordination disorder. A cognitive approach is
      multifaceted in nature and one essential component of such an approach is the use
      of cognitive strategies. Although strategy use has a long history within the
      education and psychology literature, little discussion within the pediatric
      therapy literature has occurred. This paper reports the results of an in-depth
      videotape analysis of therapists using cognitive strategies during occupational
      therapy intervention. Eight domain specific strategies were identified and
      elucidated. This research will be beneficial to therapists who wish to
      incorporate a cognitive approach into their clinical practice.

PMID- 11345508
TI  - Passport to Learning: a cognitive intervention for children with organizational
      difficulties.
AB  - Many children who are referred for therapy with school-related problems
      experience difficulty with impulsivity, task completion and the organization of
      information and ideas. School performance often improves when children learn to
      approach tasks systematically and to use cognitive strategies. In this paper, a
      short term, small group program is described that targets children's cognitive
      deficiencies and emphasizes a strategy-based, problem-solving approach to
      intervention.

PMID- 11345510
TI  - Identifying developmental coordination disorder: consistency between tests.
AB  - In the absence of a gold standard to identify the presence of developmental
      coordination disorder in children, it is useful to examine the consistency of
      different tests used in physical and occupational therapy. This study examined
      three measures of motor skills to determine whether they consistently identified
      the same children. In total, 379 children participated in this study. The final
      matched samples consisted of 202 children ranging in age from 8 to 17 years: 101
      met criteria for DCD and 101 children did not show any evidence of DCD. The
      results indicated that the overall agreement between the Bruininks Oseretsky Test
      of Motor Proficiency (BOT), the Movement Assessment Battery for Children (M-ABC)
      and the Developmental Coordination Disorder Questionnaire (DCDQ) was less than
      80%. The difference in structure and style of administration between the BOT and
      the M-ABC appears to contribute to their tendency to identify different children.
      This study emphasizes the need for therapists to use clinical reasoning to
      examine multiple sources of information about a child's abilities.

PMID- 11345511
TI  - Developmental coordination disorder: what is it?
AB  - This paper begins with a discussion of the historical basis for the concept of
      developmental coordination disorder (DCD). The definition of this disorder as it
      appears in the Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV)
      is then provided. The four diagnostic criteria proposed by the DSM-IV are used to
      describe the disorder. Problems associated with the assessment of DCD are
      discussed and suggestions for further research are identified. This is followed
      by a discussion of intervention approaches that can be used with children
      identified with DCD.

PMID- 11345512
TI  - Treatment of children with Developmental Coordination Disorder: what is the
      evidence?
AB  - Children with Developmental Coordination Disorder (DCD) experience significant
      difficulty performing everyday tasks and management of these children is a great
      source of debate. Because little is understood about the etiology of the
      disorder, treatment design has been driven by competing theories of motor
      development and motor skill acquisition. Traditional approaches to treatment have
      been based on neuromaturational, hierarchical theories and, consequently,
      therapies have focused on remeditating underlying deficits with the expectation
      of subsequent improvement in motor performance. Contemporary approaches, drawn
      from human movement science, propose that treatment methods be based on the
      assumption that skill acquisition emerges from the interaction of the child, the
      task and the environment. This paper provides a review of the treatment
      literature over the past 15 years, highlighting the fact that little evidence
      exists to suggest any one approach is better than another. Given current demands
      for evidence-based practice, and evolving concepts in skill acquisition, a
      movement toward interventions that are based on functional outcomes is
      recommended.

PMID- 11345513
TI  - Cognitive orientation to daily occupational performance (CO-OP): part I-
      theoretical foundations.
AB  - This paper is the first in a series of three papers that present the systematic
      development and evaluation of Cognitive Orientation to daily Occupational
      Performance (CO-OP). CO-OP is a cognitively based, child-centred intervention
      that enables children to achieve their functional goals. In Part I, the breadth
      of literature that provides the theoretical underpinnings for the approach is
      reviewed. Parts II and III provide a description of the approach and present the
      evidence to support its use with children with developmental coordination
      disorder.

PMID- 11345514
TI  - Cognitive orientation to daily occupational performance (CO-OP): part II--the
      evidence.
AB  - CO-OP is a child-centred, cognitive based intervention, focused on enabling
      children to achieve their functional goals. It has been developed over the last
      nine years through a series of systematic studies that have specified the
      treatment protocol and evaluated its effect. Initially CO-OP was explored in two
      series of single case experimental studies. Subsequently, an informal follow-up
      study and a detailed analysis of the video-taped sessions of the approach were
      completed. Based on information from these studies, the approach was refined, key
      features elucidated and the protocol was specified. Next, a pilot randomized
      clinical trial was completed. The trial was conducted to determine how best to
      approach a full scale randomized clinical trial on the effectiveness of CO-OP,
      relative to the current therapeutic approach. Finally, a retrospective chart
      audit was carried out to examine the cumulative evidence on the effectiveness of
      CO-OP in improving the performance of children with DCD. This paper presents a
      detailed summary of these five studies and discusses the implications of the
      findings.

PMID- 11345515
TI  - Dietary restriction stimulates BDNF production in the brain and thereby protects
      neurons against excitotoxic injury.
AB  - Dietary restriction (DR) increases the lifespan of rodents and increases their
      resistance to several different age-related diseases including cancer and
      diabetes. Beneficial effects of DR on brain plasticity and neuronal vulnerability
      to injury have recently been reported, but the underlying mechanisms are unknown.
      We report that levels of brain-derived neurotrophic factor (BDNF) are
      significantly increased in the hippocampus, cerebral cortex, and striatum of rats
      maintained on a DR regimen compared to animals fed ad libitum (AL). Seizure
      induced damage to hippocampal neurons was significantly reduced in rats
      maintained on DR, and this beneficial effect was attenuated by intraventricular
      administration of a BDNF-blocking antibody. These findings provide the first
      evidence that diet can effect expression of a neurotrophic factor, demonstrate
      that BDNF signaling plays a central role in the neuroprotective effect of DR, and
      proffer DR as an approach for reducing neuronal damage in neurodegenerative
      disorders.

PMID- 11345516
TI  - Altered immunoreactivity of HPC-1/syntaxin 1A in proliferated nerve fibers in the
      human aganglionic colon of Hirschsprung's disease.
AB  - To clarify the pathogenesis of excessive proliferation of extrinsic nerve fibers
      in the aganglionic colon of patients with Hirschsprung's disease (HD), we
      immunohistochemically determined the role that exocytosis-related proteins play
      in the regulation of exocytosis using the antibody to HPC-1/syntaxin 1A, an
      exocytosis-related protein. Localization of exocytosis-related proteins (HPC
      1/syntaxin 1A, N-ethylmalemide-sensitive fusion protein (NSF), soluble NSF
      attachment protein (SNAP), synaptotagmin, synaptobrevin, and synaptosome
      associated protein 25 (SNAP-25)) was determined in surgical specimens obtained
      from normal proximal and aganglionic distal segments of the colon of 7 infant
      patients with HD. In the normal ganglionic colon, Auerbach's plexus, Meisner's
      plexus, nerve fibers in the muscle layer, and ganglion cells were immunopositive
      for all six kinds of antisera. In the aganglionic segments, numerous proliferated
      nerve fibers and hypertrophied nerve bundles were detected in the submucosal
      layer and myenteric layer by NSF, SNAP, synaptotagmin, synaptobrevin, and SNAP
      25. However, HPC-1/syntaxin 1A was not recognized in the proliferated nerve
      fibers of the submucosal layer or the hypertrophied nerve bundles of the
      aganglionic segment. These findings show that immunoreactivity of HPC-1/syntaxin
      1A was decreased in the affected bowel segments of patients with HD and may be
      related to the pathogenesis of extrinsic nerve-fiber proliferation in the
      aganglionic colon of HD.

PMID- 11345517
TI  - Cloning and characterization of G protein-gated inward rectifier K+ channel
      (GIRK1) isoforms from heart and brain.
AB  - A G protein-gated inward rectifier potassium (K+) channel (GIRK1a) has been
      cloned from different tissues (Kubo et al., 1993b; Dascal et al., 1993). Here we
      report the cloning of three additional novel isoforms of GIRK1a from rat atria
      and and one from human brain. These isoform cDNAs code for proteins that have
      identical N-termini, M1-H5-M2 (predicted transmembrane and pore domains), and
      post-M2 amino acid regions to GIRK1a (1-501 amino acids), but they have shorter C
      termini (GIRK1b (1-309), GIRK1c (1-308), GIRK1d (1-235), and GIRK1e (1-253).
      These results indicated that isoforms were generated by alternative splicing and
      partial genomic analysis confirmed the presence of exons and introns in the rat
      GIRK1 gene. RNase protection analysis and immunoblot analysis indicated that the
      isoforms were expressed in both rat atria and brain but at lower levels versus
      GIRK1a. The physiological role that the isoforms may play in atrial and brain
      physiology remains to be determined.

PMID- 11345518
TI  - Changes in regional energy metabolism after closed head injury in the rat.
AB  - We examined in the present investigation regional ATP, glucose, and lactate
      content in the cortical and subcortical structures, in a rat model of closed head
      injury (CHI). In serial tissue sections bioluminescence imaging of ATP, glucose,
      and lactate was performed at 4 h, 12 h and 24 h (n = 4/5 per time point with)
      after the induction of CHI or sham surgery. Bioluminescence images were analyzed
      by computer-assisted densitometry, at the lesion site, in remote cortical areas,
      and in the subcortical structures (thalamus and caudate nucleus). ATP content was
      significantly decreased at the lesion site after 4 h and in the remote cortex at
      12 h post-injury. At 12 h, the ATP content reached baseline levels on the
      ipsilateral side and at 24 h also at remote lateral parietal sites. In the
      contralateral cortex, ATP increased transiently above the baseline at 12 h. No
      significant changes in ATP were found in the thalamus and caudate nucleus.
      Cortical glucose and lactate contents could not be discerned over time. Following
      CHI there is an acute and progressive, yet transient, ischemic cortical profile,
      which is not reflected in subcortical areas.

PMID- 11345519
TI  - Correlation of the clinical severity of Alzheimer's disease with an aberration in
      mitochondrial DNA (mtDNA).
AB  - Controversy exists about which of the well-established neurobiological
      abnormalities in Alzheimer's disease (AD) relate directly to the clinical
      disabilities. Because of an interest in the mitochondrial lesion in AD, we tested
      the correlation between clinical disability (measured by the Clinical Dementia
      Rating [CDR] scale) and an anomaly in mitochondrial DNA (mtDNA) in AD brain.
      Simultaneous polymerase chain reaction (PCR) amplification of the CO1 gene in
      mtDNA and CO1 pseudogenes in nuclear DNA (nDNA) were performed in samples from AD
      and non-AD brain, and the ratios of mtDNA/nDNA amplicons calculated. This
      approach utilizes PCR amplification of endogenous nDNA as a normalization
      standard for the amplification of mtDNA. We examined total DNA from the brains of
      Caucasian residents of a Jewish nursing home (86 AD and 26 non-AD "controls").
      These patients had been closely followed clinically until death and then
      autopsied. In this sample, the degree of cognitive impairment in the AD patients
      correlated with the reduction in the amplification of the mtDNA gene (p = 0.23; p
      = 0.034), but not with the density of neuritic plaques (p = 0.109). These results
      agree with the suggestion that the well-documented impairment in brain-energy
      metabolism in AD may be a direct cause of the clinical disability.

PMID- 11345520
TI  - Cyclic AMP response element binding protein (CREB) and CREB binding protein (CBP)
      in global cerebral ischemia.
AB  - Cyclic AMP (cAMP) response element binding protein (CREB) is a transcription
      factor that has been implicated in neuronal responses to ischemia. We examined
      the effect of global cerebral ischemia in the rat on the expression of CREB, its
      transcriptionally active phosphorylated form (pCREB), and the nuclear adaptor
      protein, CREB binding protein (CBP). Global ischemia induced the expression of
      pCREB and CBP in vulnerable neurons of the hippocampal CA1 sector. In primary
      cultures of murine cortical neurons subjected to hypoxia, CBP was selectively
      expressed in cells with morphologically intact cell nuclei, and not in cells with
      condensed or fragmented nuclei indicative of irreversibly damaged neurons. These
      results support a role for transcriptional activation by CREB and CBP in neuronal
      cell-survival programs following cerebral ischemia.

PMID- 11345521
TI  - Molecular strategies for fimbrial expression and assembly.
AB  - Fimbriae or pili are long, filamentous, multimeric macromolecules found on the
      bacterial cell surface. Bacteria express a diverse array of fimbriae or pili that
      are involved in bacterial adherence and invasion. Fimbriae can be categorized
      based on their modes of expression and assembly. Type I fimbriae and P pili are
      distributed peritrichously and translocated to the cell surface by a
      chaperone/usher pathway. Type 4 pili are located at the pole of the cell and
      assembled via the type II secretion system. Curli fimbriae are coiled surface
      structures assembled by an extracellular nucleation/precipitation pathway.
      Fimbriae of oral gram-negative and gram-positive bacteria have not been well
      studied as compared with the fimbriae of enteric pathogens. Oral pathogens, such
      as Eikenella corrodens, Actinobacillus actinomycetemcomitans, and Porphyromonas
      gingivalis, possess fimbriae that have been implicated in bacterial adhesion and
      invasion. These fimbriae are potential virulence factors in oral infectious
      processes. A. actinomycetemcomitans and E. corrodens have Type 4-like fimbriae,
      whereas P. gingivalis displays a unique type of fimbriae. To date, fimbriae of
      the oral primary colonizers, Actinomyces naeslundii and Streptococcus
      parasanguis, represent the only fimbriae characterized for any gram-positive
      bacteria. The putative major fimbrial subunits, FimA and FimP of A. naeslundii
      and Fap1 of S. parasanguis, contain a signal sequence and cell-wall-sorting
      signal. The presence of extensive dipeptide repeats in Fap1 makes it unique among
      fimbrial molecules. Based on experimental data, a nucleation/precipitation
      pathway is proposed for fimbrial biogenesis of both S. parasanguis and A.
      naeslundii, although we cannot rule out an alternative covalent linkage model.
      The model systems described in this review served as a framework for hypotheses
      for how the known molecular factors of fimbriae on oral bacteria may be expressed
      and assembled.

PMID- 11345522
TI  - Beyond the specific plaque hypothesis: are highly leukotoxic strains of
      Actinobacillus actinomycetemcomitans a paradigm for periodontal pathogenesis?
AB  - Actinobacillus actinomycetemcomitans is a facultative anaerobe implicated in a
      variety of periodontal diseases. Its presence is most closely associated with
      localized juvenile periodontitis (LIP), although the exact role of the organism
      in this and other periodontal diseases is not entirely clear. While A.
      actinomycetemcomitans produces several different putative virulence factors, the
      most widely studied is the leukotoxin. The leukotoxin selectively kills
      polymorphonuclear leukocytes and macrophages in vitro, constituting the host's
      first line of defense. Interestingly, even though all strains of A.
      actinomycetemcomitans have the genes encoding the leukotoxin, there is
      variability in leukotoxin expression. Differences in the structure of the
      promoter region of the leukotoxin gene operon were shown to correlate directly
      with levels of leukotoxin production. Highly leukotoxic forms appear to exhibit
      increased pathogenic potential, as evidenced by recent studies that have shown a
      significant association between the prevalence of such strains and the occurrence
      of LIP in several different populations. This represents the first demonstration
      of an association between a particular subset of a pathogenic species and a
      specific periodontal disease. Early identification of A. actinomycetemcomitans by
      microbial and genetic assays to evaluate leukotoxicity may enhance the efficacy
      of preventive and/or therapeutic techniques. Future investigations should
      continue to evaluate pathogenic variations of additional virulence factors
      expressed in vivo, not only of A. actinomycetemcomitans, but also of other
      periodontal bacteria and infectious disease pathogens.

PMID- 11345523
TI  - Involvement of T-lymphocytes in periodontal disease and in direct and indirect
      induction of bone resorption.
AB  - Periodontal disease is a peripheral infection involving species of gram-negative
      organisms. T-lymphocytes can be found in the dense inflammatory infiltrate in
      this disease. CD4+ and CD8+ T-cells are present in periodontal lesions, as are
      memory/activated T-lymphocytes. In addition, Th1- and Th2-type T-lymphocytes and
      their associated cytokines with a subtle polarization to Th1 may be present. Th1
      type T-cells up-regulate the production of pro-inflammatory cytokines IL-1 and
      TNF-alpha, which can induce bone resorption indirectly by promoting
      differentiation of osteoclast precursors and subsequently by activating
      osteoclasts. Such osteoclast differentiation is dependent on stimulation of
      osteoprotegerin ligand (OPG-L) production by osteoblastic cells. By contrast,
      activated T-cells, by virtue of direct production and expression of OPG-L, can
      directly promote osteoclast differentiation. OPG-L appears to be predominantly
      expressed on Th1-type cells. The direct and indirect T-cell involvement in
      periodontal bone resorption appears to be dependent on the degree of Th1-type T
      cell recruitment into inflamed gingival tissues. This T-cell recruitment is
      regulated by adhesion molecules and chemokines/chemokine receptors. The adhesion
      molecules involved include alpha4 and alpha6 integrins, LFA-1, and ICAM-1. The
      Th1-type T-cells preferentially express CCR5 and CXCR3, which are found
      prominently in diseased gingivae. By contrast, little CCR4, expressed by Th2-type
      T-cells, can be detected. Also, the chemokine ligands RANTES, MIP1-alpha (both
      CCR5), and IP-10 (CXCR3 ligand) were elevated in inflamed periodontal tissues.
      The T-cell features in diseased periodontal tissues can be compared with those in
      rheumatoid arthritis, wherein bone resorption often attributed to Th1-type T-cell
      involvement has also been demonstrated.

PMID- 11345524
TI  - Relation of dental composite formulations to their degradation and the release of
      hydrolyzed polymeric-resin-derived products.
AB  - This article reviews the principal modes of dental composite material degradation
      and relates them to the specific components of the composites themselves.
      Particular emphasis is placed on the selection of the monomer resins, the filler
      content, and the degree of monomer conversion after the clinical materials are
      cured. Loss of mechanical function and leaching of components from the composites
      are briefly described, while a more detailed description is provided of studies
      that have considered the chemical breakdown of materials by agents that are
      present in the oral cavity, or model the latter. Specific attention will be given
      to the hydrolysis process of monomer and composite components, i.e., the scission
      of condensation-type bonds (esters, ethers, amides, etc.) that make up the
      monomer resins, following reaction of the resins with water and salivary enzymes.
      A synopsis of enzyme types and their sources is outlined, along with a
      description of the work that supports their ability to attack and degrade
      specific types of monomer systems. The methods for the study of biodegradation
      effects are compared in terms of sensitivity and the information that they
      provide. The impact of biodegradation on the ultimate biocompatibility of current
      materials is discussed from the perspective of what is known to date and what
      remains to be studied. The findings of the past decade clearly indicate that
      there are many reasons to probe the issue of biochemical stability of composite
      resins in the oral cavity. The challenge will now be to have both industry and
      government agencies take a pro-active approach to fund research in this area,
      with the expectation that these studies will lead to a more concise definition of
      biocompatibility issues related to dental composites. In addition, the acquired
      information from such studies will generate the development of alternate
      polymeric chemistries and composite formulations that will require further
      investigation for use as the next generation of restorative materials with
      enhanced biostability.

PMID- 11345525
TI  - A possible role for the WNT-1 pathway in oral carcinogenesis.
AB  - Reductions in cell-cell adhesion and stromal and vascular invasion are essential
      steps in the progression from localized malignancy to metastatic disease for all
      cancers. Proteins involved in intercellular adhesion, such as E-cadherin and
      catenin, probably play an important role in metastatic processes and cellular
      differentiation. While E-cadherin and beta-catenin expression has been
      extensively studied in many forms of human cancers, less is known about the role
      of the Wingless-Type-1 (WNT-1) pathway in human tumors. A large body of genetic
      and biochemical evidence has identified beta-catenin as a key downstream
      component of the WNT signaling pathway, and recent studies of colorectal tumors
      have shown a functional link among beta-catenin, adenomatous polyposis coli gene
      product (APC), and other components of the WNT-1 pathway. WNT-1 pathway signaling
      is thought to be mediated via interactions between beta-catenin and members of
      the LEF-1/TCF family of transcription factors. The WNT signal stabilizes beta
      catenin protein and promotes its accumulation in the cytoplasm and nucleus. In
      the nucleus, beta-catenin associates with TCF to form a functional transcription
      factor which mediates the transactivation of target genes involved in the
      promotion of tumor progression, invasion, and metastasis, such as C-Myc, cyclin
      D1, c-jun, fra-1, and u-PAR. There is a strong correlation between the ability of
      the WNT-1 gene to induce beta-catenin accumulation and its transforming potential
      in vivo, suggesting that the WNT-1 gene activates an intracellular signaling
      pathway that can induce the morphological transformation of cells. For these
      reasons, data obtained from the study of the WNT-1 pathway could be important in
      our understanding of the mechanisms of epithelial tumors, in general, and
      probably also of oral squamous cell carcinoma, in particular.

PMID- 11345526
TI  - Regulation of mandibular postures: mechanisms and clinical implications.
AB  - This review argues that (1) the habitual mandibular position is constantly
      variable and so cannot be considered as a craniomandibular reference point, (2)
      there is no unique centric relation, (3) mandibular posture greatly depends on
      head posture, (4) clinical evaluation of the occlusal vertical dimension is
      mostly empirical, and (5) neither the vertical dimension at rest nor the centric
      relation can be determined by means of existing instrument-based clinical
      methods. However, some physiological conditions exist that facilitate the
      recording of craniomandibular position.

PMID- 11345527
TI  - Immunodominant antigens in periodontal disease: a real or illusive concept?
AB  - The humoral arm of the immune system provides protection from many medically
      significant pathogens. The antigenic epitopes of the pathogens which induce these
      responses, and the subsequent characteristics of the host response, have been
      extensively documented in the medical literature, and in many cases have resulted
      in the development and implementation of effective vaccines or diagnostic tests.
      There is a substantial body of literature on the humoral immune response in
      periodontal disease, which is targeted at micro-organisms present within
      periodontal pockets. However, the significance and specificity of the immune
      response in periodontal disease have proved difficult to elucidate, due to the
      large number of potential pathogens in the plaque biofilm and the apparent
      commensal nature of many of these opportunistic pathogens. This review addresses
      our current knowledge of the approaches and strategies which have been used to
      elucidate and examine the concept of immunodominant antigens in medical
      infections and, more recently, periodontal disease. An
      identification/understanding of the immunodominant antigens would be informative
      with respect to: (i) the relative importance of the implicated pathogens, (ii)
      new approaches to immunological diagnosis, (iii) specific bacterial virulence
      determinants, (iv) natural protective responses, and (v) the selection of
      potential vaccine candidate antigens. We conclude that immunodominance of
      antigens in periodontal disease may be relevant to our understanding of
      periodontal disease pathogenesis, but due to the complexity and diversity of the
      'pathogenic microbial ecology', it is currently an enigmatic topic requiring a
      multidisciplinary approach linking clinical, microbiological, and immunological
      investigations. We also conclude, after assessing the literature available on the
      topic of immunodominance, that it is a term that, if used, must be clearly
      defined and understood, since it is often used loosely, leading to a general
      misinterpretation by readers of oral and medical literature.

PMID- 11345528
TI  - Genetic variation in 16S-23S rDNA internal transcribed spacer regions and the
      possible use of this genetic variation for molecular diagnosis of Bacteroides
      species.
AB  - The structural variation in 16S-23S rDNA internal transcribed spacer regions
      (ITS) among Bacteroides species was assessed by PCR amplification and sequencing
      analysis, and its possible use for molecular diagnosis of these species was
      evaluated. Ninety strains of the genus Bacteroides, including the species B.
      distasonis, B. eggerthii, B. fragilis, B. ovatus, B. thetaiotaomicron, B.
      uniformis and B. vulgatus, produced one to three ITS amplification products with
      sizes ranging from 615 to 810 bp. Some Bacteroides strains could be
      differentiated at species level on the basis of ITS amplification patterns and
      restriction fragment length polymorphism (RFLP) analysis using a four-nucleotide
      recognizing enzyme, Msp I. The results of sequence analysis of ITS amplification
      products revealed genes for Ile-tRNA and Ala-tRNA in all strains tested. The
      nucleotide sequence, except for that in tRNA-coding regions, was highly variable
      and characteristic for each species, but a common sequence among B. fragilis, B.
      thetaiotaomicron and B. ovatus was observed. A digoxigenin-labeled
      oligonucleotide probe (named FOT1), which was designed from this conserved
      sequence, specifically hybridized to the ITS amplification products from B.
      fragilis, B. thetaiotaomicron and B. ovatus. These results suggest that the ITS
      region is a useful target for the development of rapid and accurate techniques
      for identification of Bacteroides species.

PMID- 11345529
TI  - Effect of sealing and Tween 80 on the antifungal susceptibility testing of
      essential oils.
AB  - Concentrations of essential oils showing high volatility decreased substantially
      in broth and agar media when incubated under open conditions. The decrease in the
      half life was from 0.7 to 38 hr in broth medium at 27 C. When evaporation was
      prevented by sealing, MIC values against Aspergillus fumigatus, Candida albicans
      and Trichophyton mentagrophytes by broth or agar dilution assay were lowered two
      to eight-fold, as compared with those obtained under open conditions. Addition of
      Tween 80 caused a rise of the MICs against A. fumigatus by two to four-fold in
      broth dilution assay, but little affected the MICs in agar dilution assay.

PMID- 11345530
TI  - Cluster analysis of human and animal pathogenic Microsporum species and their
      teleomorphic states, Arthroderma species, based on the DNA sequences of nuclear
      ribosomal internal transcribed spacer 1.
AB  - We performed a cluster analysis of human and animal pathogenic Microsporum
      species and their teleomorphic states, Arthroderma species, including A. otae
      related species (M. canis, M. audouinii, M. distortum, M. equinum, M. langeronii,
      and M. ferrugineum) and M. gypseum complex (A. fulvum, A. gypseum, and A.
      incurvatum) using DNA sequences of nuclear ribosomal internal transcribed spacer
      1 (ITS1). The dendrogram showed the members of A. otae-related species to be
      monophyletic and to construct an extremely closely related cluster with a long
      horizontal branch. This ITS1-homologous group of A. otae was organized in 6
      unique genotypes, while sequences of the members of the ITS1-homologous group of
      M. gypseum complex are more diverse. This ITS1-based database of Microsporum
      species and their teleomorphic states will provide a useful and reliable species
      identification system: it is time-saving (takes two to three days), accurate and
      applicable even to strains with atypical morphological features or in a non
      culturable state.

PMID- 11345531
TI  - Mechanism of inhibitory effect of NCC164 on replication of human immunodeficiency
      virus.
AB  - The effect of a novel anti-HIV (human immunodeficiency virus) compound,
      designated NCC164, has been studied with HIV infected cultures. The agent
      exhibited concentration-dependent inhibition of HIV replication in primary
      infected cultures of H9 cell line and PBMCs. Substantial inhibition of viral
      replication was observed at concentration of NCC164 that showed little
      cytotoxicity. The ratio of IC50 values for the MTT (3-4,5 dimethylthiazol-2,5
      diphenyl tetrazolium bromide) to RT (reverse transcriptase) assays means the
      selectivity index was more than 100. In attempting to define the inhibitory
      mechanism of NCC164, we investigated its effect on each step of HIV replication.
      This agent was highly effective against HIV replication regardless of the
      addition period during early stages of infection (adsorption to integration) but
      did not inhibit reverse transcriptase activity directly. The agent efficiently
      blocked virus maturation without side effect and the number of progeny produced
      by NCC164-treated cells was markedly reduced.

PMID- 11345532
TI  - Correlation between human herpesvirus 6 and 7 infections after living related
      liver transplantation.
AB  - Human herpesvirus 6 (HHV-6) and human herpesvirus 7 (HHV-7) are closely related
      to each other. Interaction between the two viruses at the time of primary HHV-7
      infection is suggested by in vivo and in vitro studies. However, interaction
      between the two viruses in organ transplant recipients has not been analyzed. We
      analyzed serially collected plasma samples obtained from 40 living related liver
      transplant recipients by serological assay (indirect immunofluorescence assay,
      IFA) and polymerase chain reaction (PCR). Significant increase or seroconversion
      of HHV-6 IgG and HHV-7 IgG antibody titers were observed in 45% and 58% of
      recipients respectively. Positive rate of IgM HHV-6 antibody increased up to 35%
      at 4 weeks after transplantation. However, no remarkable peak in the positive
      rate of HHV-7 IgM antibody was demonstrated. HHV-6 and HHV-7 DNA were detected in
      plasma in 15 (38%) and 16 (40%) of the 40 recipients respectively. HHV-6 DNA was
      detected in 10 (26%) of the 38 recipients at 2 weeks after transplantation. The
      positive rate of the virus genome in plasma gradually decreased after that time.
      HHV-7 DNA was detected in 5 (14%) of the 37 recipients at 2 weeks after
      transplantation; no obvious peak in the positive rate of HHV-7 DNA was
      demonstrated. Antibody responses involving both HHV-6 and HHV-7, including either
      a significant increase in IgG antibody titers or positive identification of IgM
      antibody were observed in 17 (43%) of the 40 recipients. Thirteen out of the 17
      recipients demonstrated concurrent antibody response against both viruses. HHV-7
      antibody response preceded the HHV-6 antibody response in 2 of the remaining 4
      recipients, whereas the opposite was true in the other 2 recipients. Both HHV-6
      and HHV-7 DNA were detected in 7 (18%) of the 40 recipients. In 4 of those 7
      recipients, DNA from both viruses was concurrently detected, 3 of whom had HHV-7
      DNA repeatedly detected after first detection of the virus DNA. The detection of
      HHV-7 DNA preceded the detection of HHV-6 DNA in 2 recipients, whereas HHV-6 DNA
      appeared first in 1 recipient.

PMID- 11345533
TI  - Flow cytometric evaluation of antiviral agents against human herpesvirus 6.
AB  - Antiviral activities of acyclovir (9-[(2-hydroxyethoxy) methyl] guanine, ACV),
      penciclovir (9-[4-hydroxy-3-(hydroxymethyl) butyl] guanine, PCV), ganciclovir ([9
      (1,3-dihydroxy-2-propoxy) methyl] guanine, GCV), and foscarnet (phosphonoformic
      acid, PFA) were determined against Human Herpesvirus 6 (HHV-6) by flow cytometric
      technique. The technique is based on the detection of gp116 antigen expression in
      virus infected cells. Susceptibility was defined in terms of drug concentration
      which reduced the number of cells expressing HHV-6 gp116 antigen with a mean
      fluorescent intensity (MFI) by 50% as compared to virus infected untreated cells.
      GCV was found to be most effective against HHV-6 followed by PFA, PCV and ACV.
      For HHV-6A, the mean 50% inhibitory concentrations (IC50) of GCV and PFA were
      found to be 3.4 microM and 34.7 microM respectively, whereas the IC50 of ACV and
      PCV were found to be 53.7 microM and 37.9 microM respectively. For HHV-6B, the
      IC50 of GCV and PFA were found to be 5.7 microM and 71.4 microM respectively,
      whereas the IC50 of ACV and PCV were found to be 119.0 microM and 77.8 microM
      respectively. Flow cytometry is a valuable technique for the evaluation of
      antiviral compounds against viruses including HHV-6.

PMID- 11345534
TI  - Cross-linking of beta2 integrins caused diminished responses of neutrophils to
      priming agents like lipopolysaccharide or tumor necrosis factor-alpha: possible
      involvement of tyrosine kinase Syk.
AB  - Neutrophils up-regulate beta2 integrins like CD11b/CD18 in response to
      lipopolysaccharide (LPS). Up-regulation of beta2 integrins causes neutrophils to
      adhere to surfaces, and to release superoxide anion (O2-). When neutrophils are
      exposed to LPS plus plasma under conditions not favorable for adherence (absence
      of Mg2+), the cells do not spontaneously release O2-, but instead they are primed
      for enhanced release of O2- after subsequent triggering by fMLP. In the presence
      of Mg2+, neutrophils adhere in response to LPS but fMLP-triggered O2- release by
      LPS-primed neutrophils is diminished. To understand why adherence interferes with
      the response of neutrophils to N-formyl-methionyl-leucyl-phenylalanine (fMLP),
      beta2 integrins were cross-linked by mouse monoclonal antibodies that had been
      immobilized by surface-bound anti-mouse antibody. When unprimed neutrophils were
      trapped on the surface by these cross-linked monoclonal antibodies, O2- release
      was triggered, and priming by LPS for fMLP-triggered O2- release was diminished,
      indicating that this cross-linking of beta2 integrins mimicked adherence.
      Alkaline phosphatase is up-regulated by LPS or tumor necrosis factor-alpha, and
      this response was also diminished by the cross-linking antibodies. The diminished
      alkaline phosphatase up-regulation was reversed by genistein, a general inhibitor
      of tyrosine kinases, and by piceatannol, an inhibitor for Syk kinase. Piceatannol
      also inhibited the phosphorylation of Syk caused by cross-linking of beta2
      integrins. These results suggested that adherence-induced triggering and Syk
      kinase activation might be responsible for the diminished response of LPS-primed
      neutrophils to fMLP when neutrophils were adherent.

PMID- 11345535
TI  - Location of the epitope for 7D5, a monoclonal antibody raised against human
      flavocytochrome b558, to the extracellular peptide portion of primate gp91phox.
AB  - Flavocytochrome b558 is the membrane component of the phagocyte NADPH oxidase,
      and is a heterodimer composed of gp91phox and p22phox subunits. Human
      flavocytochrome b558 is recognized by monoclonal antibody 7D5 at an unidentified
      extracellular domain, although our previous study suggested it might recognize
      p22phox. 7D5 has proven useful in rapid screening of individuals for X-linked
      chronic granulomatous disease by flow-cytometry. Therefore, we re-evaluated the
      location of the 7D5 epitope using gene-engineered cell lines expressing hybrid
      flavocytochromes composed of human and murine subunit homologues. The current
      study demonstrates that the 7D5 recognizes epitope only of primate gp91phox. Flow
      cytometric analyses showed that 7D5 consistently bound to cells expressing human
      gp91phox. In addition, 7D5 immunoprecipitated the approximately 58 kDa
      unglycosylated gp91phox protein from solubilized membrane fractions of
      tunicamycin-treated PLB-985 granulocytes, indicating that glycans were not
      required for 7D5 binding. Transgenic COS7 cells expressing human gp91phox but not
      p22phox were recognized by 7D5. These results localized the epitope of 7D5 to an
      extracellular peptide portion of primate gp91phox and indicate that the antibody
      will be useful for monitoring the efficiency of gene therapy in patients with
      flavocytochrome b558-deficient chronic granulomatous disease and for elucidating
      structural characteristics of flavocytochrome b558.

PMID- 11345536
TI  - Adhesion of Bifidobacterium spp. to human intestinal mucus.
AB  - Twenty-four Bifidobacterium strains were examined for their ability to bind to
      immobilized human and bovine intestinal mucus glycoproteins. Each of the tested
      bacteria exhibited its characteristic adhesion to human and bovine fecal mucus.
      No significant differences were found among the taxonomic species. Among the
      tested bacteria, B. adolescentis, B. angulatum, B. bifidum, B. breve, B.
      catenulatum, B. infantis, B. longum and B. pseudocatenulatum adhered to human
      fecal mucus better than bovine fecal mucus, while the binding of B. animalis and
      B. lactis was not preferential. These results suggest that the mucosal adhesive
      properties of bifidobacteria may be a strain dependent feature, and the mucosal
      binding of the human bifidobacteria may be more host specific.

PMID- 11345537
TI  - PCR detection method of Clostridium scindens and C. hiranonis in human fecal
      samples.
AB  - Clostridium scindens and C. hiranonis have high bile acid 7alpha-dehydroxylating
      activity. Direct PCR and nested PCR with the specific primers for C. scindens and
      C. hiranonis were developed and tested for the detection of them in human fecal
      samples. Nested PCR detected C. scindens in all samples, but direct PCR detected
      it in 27 of 34 samples. Regarding C. hiranonis, nested PCR detected it in only 18
      of 34 samples although nested PCR has a high level of sensitivity. Nested PCR was
      a specific and sensitive method for the detection of C. scindens and C. hiranonis
      in fecal samples.

PMID- 11345538
TI  - Investigation of varicella-zoster virus DNA in lymphocyte subpopulations by
      quantitative PCR assay.
AB  - To investigate the nature of viremia during the acute phase of varicella, we
      studied the viral load in nine otherwise healthy children with varicella. Plasma
      and peripheral blood mononuclear cells (PBMC) were obtained, then PBMC were
      divided into CD4+T, CD8+T, and B lymphocytes and monocyte/macrophage fractions.
      The viral DNA in each component was quantified using a real-time quantitative
      polymerase chain reaction assay. Varicella-zoster virus (VZV) DNA was detected in
      plasma, PBMC and all subpopulations. The amount of viral DNA was similar in each
      PBMC subpopulation, suggesting that each lymphocyte fraction and monocytes carry
      similar amounts of VZV DNA during viremia.

PMID- 11345540
TI  - Acute cytotoxicity assessment of liquid samples using rainbow trout (oncorhynchus
      mykiss) hepatocytes.

PMID- 11345539
TI  - Airborne fungal ecological niche determination as one of the possibilities for
      indirect mycotoxin risk assessment in indoor air.
AB  - Based on the microbiological analysis of air samples from occupied spaces, some
      possibilities for indirect risk assessment of mycotoxin-related health problems
      are proposed. Airborne fungi could be classified on the basis of the relationship
      between the two environmental factors and their combinations, i.e., temperature
      and water requirements (water activity aw). One type involves three different
      groups of molds, selected on the basis of the quantitative and qualitative
      information about the ability of fungi to sporulate under different environmental
      conditions: group (i), represented by Aspergillus nidulans, A. niger, and A.
      ochraceus, and characterized by sporulation which was more dependent on
      temperature than on water activity; (ii), represented by A. flavus and A.
      versicolor, in which sporulation was approximately equal and depended on both the
      temperature changes and aw alterations; and (iii), represented by Cladosporium
      sp., Penicillium cyclopium, and P. citrinum, in which sporulation depended more
      on alteration of the aw conditions than on temperature changes. Another type is
      characterized by four sporulation rates with two levels of mycotoxin risk
      accumulation in the spores (conidia) of each mold species: large (Ia) and
      moderate (Ib) sporulation rates with a risk of mycotoxin accumulation (aw > or =
      86; t > or = 12 degrees C); rare sporulation (IIa) and absence of sporulation
      (IIb), without risk of mycotoxin accumulation (aw < or = 86; t < or = 12 degrees
      C). In conclusion, providing a useful guide for two dimensions, temperature and
      water activity for each of the three phases of fungal growth, i.e. germination,
      growth, and sporulation, could be important for determination of the fundamental
      niche of each fungus and its ability to form or accumulate mycotoxin. Special
      emphasis should be given to the indirect mycotoxin risk assessment in heating,
      ventilation, and air conditioning systems.

PMID- 11345541
TI  - First report of a microcystin-containing bloom of the cyanobacterium microcystis
      aeruginosa in the La Plata River, South America.

PMID- 11345542
TI  - Sediment quality assessment survey and toxicity identification evaluation studies
      in Lavaca Bay, Texas, a marine Superfund site.
AB  - A sediment quality assessment survey was conducted in Lavaca Bay, Texas, in
      proximity to a marine Superfund National Priority List (NPL) site. Previous
      studies at this site had focused primarily on the degree and extent of mercury
      contamination. The purpose of this survey was to determine the potential
      ecotoxicological impacts of contaminants, using sensitive sediment toxicity tests
      in conjunction with a comprehensive chemical analysis of the sediments. In
      addition, phase I toxicity identification evaluation (TIE) studies were conducted
      at several of the more toxic sites. Sea urchin (Arbacia punctulata) fertilization
      and embryological development tests with sediment pore water were employed to
      assess the toxicity of the sediments. Elevated levels of mercury were found in a
      number of samples as much as 10-20 times that of background. Six stations had
      total polycyclic aromatic hydrocarbon (PAH) concentration above the probable
      effect level (PEL) guideline value, and some stations had concentrations as much
      as 1000 times above background levels. Eighteen of the 24 stations exhibited
      toxicity in one of the toxicity tests, while 14 stations were toxic in both
      tests. A number of stations within the fish closure area exceeded 8-16 of the PEl
      guidelines. Both aeration and the C18 column treatments were effective in
      reducing toxicity from the pore water of the two stations included in the TIE.
      This information, in conjunction with the fact that two of the four stations with
      the highest mercury concentrations were not toxic, suggests that the toxicity
      observed in this study is primarily due to organics, probably PAHs, and not
      mercury. We recommend that these other contaminants of concern be considered in
      any remedial actions that are planned for this NPL site and that impacts on the
      ecosystem, as well as human health issues, also be considered.

PMID- 11345543
TI  - Toxicant interactions with food algae: a missing link between laboratory and
      field effects?
AB  - Algae fed to invertebrate subjects of chronic toxicity testing are cultured
      without exposure to test substances. This approach may reduce the ability of
      bioassays to predict field effects because it assumes that bioconcentration is
      the only important uptake route, and that an interaction between toxicant and
      algae does not occur or is not relevant to the effect of the toxicant on test
      animals. The research presented in this paper focuses on the effects of a
      bleached kraft mill effluent (BKME) on algae used as food for test animals and
      the possible consequences of this exposure to bioassay results. The experiment
      consisted of exposing cultures of a pennate diatom, Navicula, to a range (0-7%)
      of BKME concentrations for 15 days. Final biomass (measured as chlorophyll a and
      ash free dry mass) was significantly greater in cultures exposed to 5% and 7%
      BKME. The carbon-to-nitrogen ratio was significantly higher in diatom cultures
      exposed to 7% BKME, and total lipid content ranged from 11.7% in the control to
      15.8% in the 7% treatment. BKME exposure also increased bacterial content and
      altered the elemental composition (particularly strontium, barium, iron, and
      cobalt) of Navicula relative to control cultures. Because changes in food
      abundance and food quality (e.g., dietary lipids, carbohydrates, proteins) are
      known to modify toxicity and because contaminant uptake can occur through
      ingestion, exposing algal food supplies to toxicants would allow chronic
      bioassays to better simulate field conditions. This approach would be of value in
      situations where bioassays are intended to predict field effects rather than to
      compare the toxic potential of effluent samples. Although culturing food algae
      under exposure to contaminants poses methodological challenges, this approach may
      serve to enhance the predictive ability of chronic bioassays.

PMID- 11345544
TI  - Effect of 2,4-dichlorophenoxyacetic acid herbicide on escherichia coli growth,
      chemical composition, and cellular envelope.
AB  - 2,4-Dichlorophenoxyacetic acid (2,4-D) is a herbicide widely used in the world
      and mainly excreted by the renal route in exposed humans and animals. Herbicides
      can affect other nontarget organisms, such as Escherichia coli. We observed that
      a single exposure to 1 mM 2,4-D diminished growth and total protein content in
      all E. coli strains tested in vitro. In addition, successive exposures to 0.01 mM
      2,4-D had a toxic effect decreasing growth up to early stationary phase.
      Uropathogenic E. coli adhere to epithelial cells mediated by fimbriae, adhesins,
      and hydrophobic properties. 2,4-D exposure of uropathogenic E. coli demonstrated
      altered hydrophobicity and fimbriation. Hydrophobicity index values obtained by
      partition in p-xylene/water were 300-420% higher in exposed cells than in control
      ones. Furthermore, values of hemagglutination titer, protein contents in fimbrial
      crude extract, and electron microscopy demonstrated a significant diminution of
      fimbriation in treated cells. Other envelope alterations could be detected, such
      as lipoperoxidation, evidenced by decreased polyunsaturated fatty acids and
      increased lipid degradation products (malonaldehyde), and motility diminution.
      These alterations decreased cell adherence to erythrocytes, indicating a
      diminished pathogenic capacity of the 2,4-D-exposed E. coli.

PMID- 11345545
TI  - Structure-activity relationships for aquatic toxicity to Tetrahymena: halogen
      substituted aliphatic esters.
AB  - The toxicity of a series of 21 mono- and dihalogenated aliphatic monoesters has
      been evaluated using a Tetrahymena pyriformis population growth impairment assay.
      A structure-activity model has been developed for toxicity data (log(IGC50(-1))),
      using the 1-octanol/water partition coefficient (logKow) and the energy of the
      lowest unoccupied molecular orbital (ELUMO) as descriptors. A statistically
      robust plane (log of the inverse of the 50% growth inhibitory concentration
      (IGC50(-1)) = 0.34logKow - 0.84 (ELUMO) + 0.04; n = 15, r2 = 0.85, s = 0.26, F =
      33, Pr > F = 0.0001) was found for monohalogen-substituted derivatives. These
      substances are thought to exhibit toxicity via the soft electrophilic mode of
      toxic action. This toxicity is imparted by the leaving ability of the halogen,
      which is enhanced when it is placed in close proximity to the carbonyl group.
      This leaving ability allows haloesters, especially alpha-haloesters, to undergo
      an SN2, addition-elimination substitution electro(nucleo)philic reaction.
      Outliers to the above model broadly fell into two groups: small reactive
      molecules (e.g., propylbromoacetate) that were more toxic than predicted and
      molecules in which the reactive center was sterically hindered by an alkyl group
      (e.g., ethyl-2-bromoisovalerate), which were less toxic than predicted.

PMID- 11345546
TI  - Lead toxicity in cyanobacterial porphyrin metabolism.
AB  - The effect of Pb2+ on growth, tetrapyrrole photosynthetic pigment content, total
      free porphyrin, and 5-aminolevulinate dehydratase (ALA-D) activity of a
      cyanobacterium, Microchaete tenera, and its ability to sequester Pb2+ from the
      culture medium were studied. Pb2+ was assayed by graphite furnace atomic
      absorption spectrophotometry. M. tenera growth and chlorophyll a content were not
      affected by 0.5, 1.0, and 6.0 ppm of Pb2+. These treatments doubled the protein
      content and increased the phycobiliprotein content by four times after 7 days.
      The ALA-D activity decreased in all concentrations by 63% at day 7 and by 34% at
      day 14. As a consequence of ALA-D inhibition, total free porphyrin also decreased
      by 64% at day 7 and by 40% at day 14. The highest biomass lead uptake (7454 +/-
      565 micrograms Pb2+/g dry weight) was observed at day 3 with 6.0 ppm of Pb2+ in
      the culture medium. Uptake coefficient was highest (3723 +/- 279 micrograms Pb2+
      g-1 dry weight/ppm of applied Pb2+) with 1.0 ppm after 3 days. The increase in
      protein and antenna pigments on day 7 was probably a response to stress
      conditions and could explain why the toxic metal did not affect growth. ALA-D
      inhibition and high lead biomass content confirm the importance of this enzyme as
      a biological indicator for stress.

PMID- 11345547
TI  - An assessment of the feasibility of using image analysis in the oyster embryo
      larval development test.
AB  - In this study the feasibility of using the latest image capture, processing, and
      analysis techniques in the oyster embryo-larval development (OEL) test was
      assessed. This initially involved determining whether the OEL test could be
      carried out in multiwell plates (which would assist in the application of the
      image analysis technique), based on data from tests with the reference toxicant
      zinc and industrial effluents. The study then ascertained which of the 31 image
      analysis parameters of the Image Pro Plus software used was most appropriate for
      differentiating between the D larvae and non-D larvae at the end of the test
      procedure in a manner similar to that of visual observations. On the basis of the
      zinc reference toxicant and effluent test data derived in this study, the OEL
      test can be effectively carried out in 24 chamber multiwell plates, which
      provides the opportunity to count objects with image analysis software. The use
      of the image analysis parameters area and size (length) in combination resulted
      in mean control abnormalities and EC50 values in zinc reference toxicant tests
      which were not significantly different statistically from corresponding values
      derived using visual observations. Discrimination using the area and length
      parameters may be improved by the inclusion of other parameters in a suite of
      measurements which would reduce interference from extraneous material or lighting
      artefacts. Furthermore, the use of multiwell plates and image analysis can
      eliminate the variability associated with sub-sampling and inter-operator
      differences in the counts of D larvae and non-D larvae which is evident with the
      current visual observation method.

PMID- 11345548
TI  - Applicability of growth rate, cell shape, and motility of Euglena gracilis as
      physiological parameters for bioassessment at lower concentrations of toxic
      substances: an experimental approach.
AB  - The responses of the growth rate, motility, and cell shape in the green
      flagellate Euglena gracilis to different concentrations of waste water substances
      from the pulp and paper industry were tested in a long-term study (7 days).
      Samples before (uncleaned sample) and after (cleaned sample) the treatment in a
      cleaning system were studied. The influence of different doses of UV-B radiation
      on cell shape and motility was also investigated. No statistically significant
      effects of increasing concentrations of the waste substances both before and
      after the cleaning process (except inhibition by the undiluted uncleaned
      effluent) on the growth rate in E. gracilis were observed. Cell shape turned out
      to be an unreliable physiological parameter for assessing the toxicity at lower
      concentrations of waste water substances. No significant patterns could be
      observed in the response of the cell shape to the different concentrations of the
      waste water substances or to UV-B radiation. Motility has been concluded to be a
      more sensitive parameter than cell shape. However, no clear patterns were
      observed in the response of the motility to the different concentrations of the
      waste water substances studied. Increasing concentrations of the uncleaned sample
      demonstrated a defense against UV-B radiation, due to the high absorbance in the
      UV-B range, when effects on motility were examined. We conclude that contrary to
      the results reported in the literature earlier, cell shape and motility of E.
      gracilis are not universal physiological parameters for bioassessment at lower
      concentrations of toxic substances, including metals such as copper and zinc from
      the pulp and paper industry. The long-duration tests had, in general, higher
      significance than those of short duration.

PMID- 11345549
TI  - Effects of dissolved carbon dioxide on the physiology and behavior of fish in
      artificial streams.
AB  - A new technology for treating waters contaminated with acid mine drainage
      involves the dissolution of limestone particles using carbon dioxide at pressures
      above ambient. Because of the fish health risks associated with episodes of high
      carbon dioxide levels in treated waters, we subjected three species of fish,
      brook trout (Salvelinus fontinalis), slimy sculpin (Cottus cognatus), and
      blacknose dace (Rhinichthys atratulus), to 24 h exposures of elevated dissolved
      carbon dioxide (CO2) at three levels, ranging from 1.0 (low) to 6.3 (high)%,
      under laboratory conditions. We measured blood physiological variables as well as
      behavior, including feeding responses, before, during, and after exposure.
      Physiological responses differed by species, but all species had elevated
      hematocrits after 1 h of exposure. Brook trout hematocritis were higher at medium
      and high levels of CO2 than in a control group (0.0% CO2) after 24 h of exposure.
      Slimy sculpin hematocrits were higher in medium- and high-level exposure groups
      than in controls after 1 h, but not after 24 h, of exposure. Blacknose dace
      hematocrits were higher in all three exposure groups than in controls after 1 h
      but only in medium-level exposure groups after 24 h. Brook trout plasma glucose
      was significantly higher in medium- and high-level exposure groups after 1 h, and
      in the high-level group after 24 h, than in controls. Slimy sculpin plasma
      glucose was not significantly different in elevated CO2 exposure groups from that
      of controls throughout exposure. Branchial ventilation was significantly greater
      in all species at elevated CO2 during exposure, indicating stress; however, no
      difference was observed between treatment and control groups of blacknose dace
      after 24 h, indicating acclimation. Pectoral fin beats and cough rates were not
      consistently related to CO2 exposure throughout the study. Brook trout had the
      longest lasting reaction to stress at lower levels of CO2 among the three species
      tested. Many of the 11 observed behavioral variables, related to swimming,
      feeding, social, and illness factors, were affected by elevations of dissolved
      CO2. Two to seven behavioral variables (18-64% of those measured) were affected
      by treatment level of dissolved CO2 with a trend by species for the number of
      variables affected: brook trout > blacknose dace > slimy sculpin. However,
      behavioral sensitivity to treatment level was greatest in blacknose dace.
      Recovery to pre-treatment activity rates for most behavior patterns (including
      feeding) was observed 24 h after cessation of exposure in all three species.
      Recovery was independent of treatment level, was most rapid in blacknose dace,
      and was slowest in brook trout. Overall, slimy sculpin was least affected
      behaviorally by elevated CO2. Although all three species showed stress response
      and changes in behavior at moderate levels of CO2 (> or = 2%), brook trout and
      blacknose dace showed evidence of ability to avoid harmful CO2 levels by swimming
      out of affected waters, whereas the slimy sculpin showed minimal behavioral
      changes despite remaining in place during exposure. Thus, predation risk and
      other sources of mortality seem minimal in the event of technological malfunction
      at a stream treatment site involving the use of CO2 under pressure.

PMID- 11345550
TI  - Fluorescent Pseudomonas isolates from Mississippi Delta oxbow lakes: in vitro
      herbicide biotransformations.
AB  - Fluorescent pseudomonads were a major component [log (10) 4.2-6.1 colony-forming
      units mL-1] of the culturable heterotrophic gram-negative bacterioplankton
      observed in three Mississippi Delta oxbow lakes in this study. Pure cultures of
      fluorescent pseudomonads were isolated from three Mississippi Delta oxbow lakes
      (18 per lake), using selective media S-1. Classical physiological tests and
      Biolog GN plates were used in criteria for taxonomic identification. Most
      isolates were identified as biotypes of Pseudomonas fluorescens 55% (II), 7%
      (III), and 25% (V). About 7% of the isolates were identified as P. putida and 7%
      as non-fluorescent Pseudomonas-like. Cell suspensions of these isolates were
      tested for their ability to metabolize/co-metabolize six 14C-radiolabeled
      herbicides (2,4-dichlorophenoxyacetic acid (2,4-D), cyanazine, fluometuron,
      metolachlor, propanil, and trifluralin) that are commonly used for crop
      production in this geographical area. Almost all (53 of 54) isolates transformed
      trifluralin via aromatic nitroreduction. Most isolates (70%) dechlorinated
      metolachlor to polar metabolites via glutathione conjugation. About 60% of the
      isolates hydrolyzed the amide bond of propanil (a rice herbicide) to
      dichloroaniline, with the highest frequency of propanil-hydrolyzing isolates
      observed in the lake from the watershed with rice cultivation. All propanil
      hydrolyzing isolates were identified as P. fluorescens biotype II. No metabolism
      of cyanazine or fluometuron was observed by any isolates tested, indicating
      little or no potential for N-dealkylation among this group of bacterioplankton.
      No mineralization of 2,4-D labeled in either the carboxyl or ring position was
      observed. These results indicate that reductive and hydrolytic pathways for
      herbicide co-metabolism (aromatic nitroreduction, aryl acylamidase, and
      glutathione conjugation) are common in Mississippi Delta aquatic fluorescent
      pseudomonads; however, the potential for certain oxidative transformations (N
      dealkylation, cyano group oxidation) may be rare in this group of
      bacterioplankton.

PMID- 11345551
TI  - The use of outdoor freshwater pond microcosms. III. Responses of phytoplankton
      and periphyton to pyridaben.
AB  - An outdoor freshwater microcosm study was conducted in which pyridaben, an
      insecticide-miticide, was directly applied to water to determine its biological
      effects on phytoplankton and periphyton. Twenty-four microcosms (24 m3 each) were
      monitored for 11 months, then four treatments of pyridaben were applied two times
      at three concentrations (0.34, 3.4, 34.0 micrograms/L), including an untreated
      control. The succession of algal groups observed and the major genera found in
      microcosms during the baseline phase of the study were typical of oligo
      mesotrophic systems in Florida. Following application of pyridaben, the most
      remarkable effect was a positive correlation of phytoplankton abundance with
      pyridaben concentrations in water; indicating increased abundance as a result of
      exposure. Both Chlorophyta and Pyrrophyta exhibited a significant increase (p =
      0.05) in population abundance at 3.4 and 34.0 micrograms/L pyridaben. Chrysophyta
      also elicited a trend of increased abundance at 34.0 micrograms/L, although the
      effect was not significant. The effects on phytoplankton populations were
      associated with the decline of zooplankton populations as a result of a direct
      effect of pyridaben exposure. There were no effects of pyridaben on periphyton
      communities or on functional endpoints.

PMID- 11345552
TI  - [Doctors, scientists and patients confront human biological materials research].

PMID- 11345553
TI  - [Chaos theory in medicine].

PMID- 11345555
TI  - [From diagnosis of asthma to chronic disease].
AB  - Asthma patients, in their daily life, may experience 3 different situations
      needing 3 types of management: attack (which is an emergency issue); post-attack
      period (very often under-diagnosed and under-treated, what is one of the major
      relapse factors); stable state (which should be the "natural" state of any
      chronic patient). Despite the availability of very active treatments, asthma
      still represents an handicap for many patients, and mortality rates go unchanged.
      All this has lead to issue asthma severity scales and consensus therapeutic
      management guidelines. Promoting and implementing these guidelines is the only
      way for improving asthma management.

PMID- 11345556
TI  - [First consultation for asthma].
AB  - The first medical visit is an essential moment of asthma management because it is
      a chronic disease needing a long term follow-up. This initial assessment which
      takes time, can be done gradually, on several days or even weeks. Once the
      differential diagnosis is excluded, the diagnosis of asthma is confirmed and its
      severity assessed. The identification of precipitant factors of asthma
      exacerbations goes through a detailed interview. Planning a therapeutic and
      supervision strategy with the patient has for goal the control of the disease and
      improvement of quality of life. Including the patient in the management of his
      asthma is only possible if he has been educated, patient education must be
      controlled and reinforced all the long of further medical visits.

PMID- 11345557
TI  - [Asthma followup in consultation].
AB  - Development and application of guidelines for asthma management and prevention
      should prevent exacerbation, avoid hospitalisations, maintain an optimal lung
      function, and guarantee a good quality of life in asthmatic patients.
      Unfortunately, there is a gap between these objectives and the patient's
      perspectives because of difficulties to organise and deliver care with the issues
      of the health professional formation, patient education and compliance to chronic
      treatments. The objectives of the follow-up visit for asthmatic patients are
      three fold: check for the control of asthma, review and optimise medical
      treatment, and control asthma management skills. Self-monitoring based of
      symptoms and/or peak expiratory flow recordings coupled with a written action
      plan and regular medication review has been shown to significantly reduce
      exacerbation rate and allows a control of the disease.

PMID- 11345558
TI  - [Acute asthma attack].
AB  - A severe form of exacerbation of asthma, AAA is defined by the presence of a
      least one sign of clinical severity during the attack. AAA is often preceded by
      prodromal symptoms that should indicate the need to increase maintenance
      treatment and eliminate possible triggering factors. Initial treatment of AAA
      should be made as early as possible and should associate high-dose oxygen,
      nebulisations of beta-2-agonists and corticosteroid infusion. The immediate
      prognosis of AAA is particularly related to the initial response to appropriate
      treatment. When objective improvement criteria are met, discharge can be
      considered, with short-term outpatient corticosteroid treatment. In more severe
      stages, beta-2 agonists and anti-cholinergic agent nebulisations are useful. The
      interest of using other bronchodilators (adrenalin, theophylline) is debated. In
      case of very severe asthma attack, inhalation of a mixture of helium and oxygen
      can avoid the need for intubation and mechanical ventilation. Subsequent to AAA,
      rehabilitation and pulmonary follow-up are indicated in order to prevent
      recurrence.

PMID- 11345559
TI  - [Asthma and allergy].
AB  - Allergy is routinely taken into account in asthma. The allergic reaction is based
      on Th2 lymphocytes specific to the allergen, which induce production of E
      immunoglobulins (IgE) and activation of eosinophils. In atopic asthma, domestic
      allergens are more often responsible than pollen. They play a part early in the
      development of the disorder, and subsequently as factors triggering
      exacerbations. Work-related asthma should always be suspected. History-taking
      should seek the relevance of allergens in the clinical manifestations, confirmed
      by skin tests, and if necessary assessment of specific IgE. Provocation tests
      should be used only diagnosis of work-related asthma. Removal of allergens should
      be suggested. Specific desensitisation may be indicated in order to decrease high
      dosage drug treatment. Rhinologic treatment is part of patient management.
      Treatments being developed include the use of anti-IgE antibodies, anti
      interleukin (IL)-5, soluble IL-4 receptors and recombinant allergens.

PMID- 11345560
TI  - [Etiology of asthma].
AB  - Asthma is a chronic inflammatory disease of the airways which occurs in
      genetically predisposed individuals. This common disease has an epidemic
      progression in western countries. Despite the identification of several candidate
      genes, genetic modifications cannot explain the recent increase in asthma
      prevalence and severity in the last forty years. Environmental factors are likely
      to be the cause of the progression of this epidemic inflammatory disease.

PMID- 11345561
TI  - [Anti-asthma drugs].
AB  - With respect to their main mechanism of action, anti-asthma drugs are classified
      as bronchodilators or anti-inflammatory drugs. Inhaled beta 2-agonists are the
      most effective bronchodilators. The shorts acting beta 2-agonists are used for
      the relief of acute symptoms whereas long acting beta 2-agonists are used on a
      regular basis, concomitantly with inhaled corticoids, for long-term control of
      symptoms. The others bronchodilators (methylxanthines or anticholinergics) may be
      used in addition to the inhaled beta 2-agonists. The treatment of bronchial
      inflammation is required in mild to severe persistent asthma. Inhaled corticoids
      are the main anti-inflammatory drugs. They have a low risk of adverse events at
      usual dosages. Anti-leukotrienes belong to a new class of anti-inflammatory drugs
      represented by montelukast in France. This drug is orally administered, well
      tolerated and used in addition to inhaled corticoids. Cromones and ketotifen are
      used only in mild persistent asthma. Inhaled beta 2-agonists, anti-leukotrienes
      and cormones are also used for prevention of exercise-induced asthma.

PMID- 11345562
TI  - [Recommendations for the management of asthma].
AB  - Recommendations for the management of asthma have been proposed for the last 15
      years around the world. These recommendations have been internationalised and the
      latest one, the Global Initiative for Asthma (GINA) is a World Health
      Organisation--National Institutes of Health initiative. Asthma recommendations
      were initially based on opinion of experts but the newest will be evidence-based.
      The GINA guidelines concern diagnosis, assessment of severity and treatment of
      asthma. They include all parts of asthma treatment: allergen avoidance,
      immunotherapy, pharmacotherapy and education. These guidelines are applied in
      over 100 countries worldwide, and, in countries where they are applied, morbidity
      and mortality due to asthma have decreased.

PMID- 11345563
TI  - [Integrity].

PMID- 11345564
TI  - [Trisomy 21. Epidemiology, diagnosis, prognosis].

PMID- 11345565
TI  - [Dysphonia].

PMID- 11345566
TI  - [Severe acute intoxication by barbiturates, tranquilizers, tricyclics,
      paracetamol, salicylates. Diagnosis, treatment].

PMID- 11345567
TI  - [Paget's disease of bone. Diagnosis, prognosis].

PMID- 11345568
TI  - [Circulatory arrest. Diagnostic approach and management with drug dosage].

PMID- 11345569
TI  - Integrating esthetic dentistry and space closure in patients with missing
      maxillary lateral incisors.

PMID- 11345570
TI  - Differentiated orthodontic mechanics for dental midline correction.

PMID- 11345571
TI  - SureSmile technology in a patient--centered orthodontic practice.

PMID- 11345572
TI  - Effects of the pendulum appliance on the dentofacial complex.

PMID- 11345573
TI  - Bicuspid tubes.

PMID- 11345574
TI  - Disposable archwire rulers.

PMID- 11345576
TI  - [On the trail of Thure von Uexkull. A brief portrait].

PMID- 11345577
TI  - [Being a body and having a body--background of dualism in medicine].
AB  - Psychosomatic medicine coincides with the detection that the medical crisis is a
      philosophical one as medicine prescribes single-track empirical models and
      concepts.  To overcome this dualism of soul-less bodies and body-less souls is of
      utmost importance in order to gain an idea reflecting man and his body in the
      reality of their firsthood experiences, secondhood acts and treatments.  In the
      realm of this reality we treat our bodies according to the reactions on warning
      signals of everyday life.  Only if our secondhood possibilities fail we have to
      see a doctor.  Thus it is the patient who gives the treatment order and nobody
      else.  He delegates his secondhood possibilities to the physician.  And the
      physician has to build up a communication enabling the construction of a mutual
      reality in which it becomes possible to reach the firsthood requirements of the
      patient via empathy.  The medical crisis as a sign of the transition from
      industrial to communication society requires from us to transfer the idea of a
      body which can be interpreted and manipulated technically into an idea of the
      body as an open information system the basis of which is the relation among
      patient, physician and disturbance or in short: the patient-physician
      relationship.  In the realm of this relationship the reality of medicine is
      emerging.  Physician therefore are called upon to defend the inseparable basis of
      their profession against expanding bureaucratisation and against marketing
      tendencies of health companies.

PMID- 11345578
TI  - [The model of the non-trivial machine or the semiotic alternative. Remarks to Th.
      v. Uexkulls and W. Weisiacks regarding the theoretical basis of human medicine].
AB  - The authors discuss the attempt by v. Uexkull and Wesiack to formulate the basics
      of human medicine within the framework of a sign theory. They criticize this
      attempt mainly in three points: 1. Central concepts of their model--i.e.
      "meaning", "sign" or "signcoupling"--are only used as general concepts and not in
      the differentiated manner they are conventionally used in semiotics. 2. Human
      behavior is reduced to conditioned reflex systems which are merely described in a
      different, semiotic way. 3. Problems evolving from the epistemology of a radical
      constructivism on which their model of a "bio-psycho-social medicine" is based,
      remain not only unsolved but also undiscussed.

PMID- 11345579
TI  - [Comments on the situation cycle of Thure von Uexkulls from the viewpoint of
      affect psychology].
AB  - The "Situationskreis" represents some of the most important parts of the
      psychosomatic theory-formation. It describes the relationship between individual
      and environment as a "cyclic" process of interpretation, which is characterized
      of an inner tentative action. Uexkull indeed mentions affective aspects in his
      "Situationskreis", but doesn't apply them consequently. From a psychology of
      affects and emotions several additional points are possible; first in the meaning
      of non-verbal moments, then in a differentiation of the constructivistic
      position, in the assumption of internalization terms, in a radicalisation of the
      historical statement and in problematizing the demanded method.

PMID- 11345580
TI  - [The role of implicit knowledge in therapeutic change. Some implications of
      developmental observations for adult psychotherapy].
AB  - Several aspects of development change that are dependent on interactions between
      parent and infant are examined for their value in casting light on the process of
      change in adult psychotherapies. First, the domain of implicit knowledge (where
      changes necessarily occur in nonverbal infants) is identified. The vast majority
      of therapeutic change is found to occur in this domain. We then examine the
      improvised, largely unpredictable, nonlinear environments toward mutual goals
      that characterize the process of parent-infant and therapist-patient
      interactions. Finally, we provide a microdescription of these processes and
      provide a terminology for the "moments" that make up their flow. Of particular
      importance is the "moment of meeting", in which the participants interact in a
      way that created a new implicit, intersubjective understanding of their
      relationship and permits a new "way-of-being-with-the-other". We view "moments of
      meeting" as the key element in bringing about change in implicit knowledge, just
      as interpretations are thought to be the key element in bringing about change in
      explicit knowledge.

PMID- 11345581
TI  - [Perceived threat related to dental amalgam fillings].
AB  - Amalgam carriers without somatic complaints and patients who attribute symptoms
      to amalgam fillings of their teeth do not differ with respect to toxicologic or
      allergologic parameters. Somatic complaints of amalgam carriers usually are
      explained as misattributions of unspecific complaints. Perceived threat is a
      relevant factor within the theoretical models. For the explanation of health
      related behavior perceived threat is also an important variable. In the present
      study perceived threat was a relevant factor for complaints associated with
      dental material, but not for health related behavior in the sense of caries
      prophylaxis.

PMID- 11345582
TI  - [Psychosocial intervention to help child and adolescent witnesses in court].
AB  - The risk of crimes being committed against children and adolescents is
      particularly high. These individuals should receive effective protection.
      Confronted with judicial proceedings, they are exposed to enormous amounts of
      stress. Often they are overwhelmed by feelings of fear and insecurity. Secondary
      victimization is likely to follow as a result of the negative experiences they
      encounter with the judicial system. A victim assistance program has been set up
      in the regional and district court of Dusseldorf in order to protect against such
      trauma. Forty-seven child and adolescent victims and 53 adult victims, all turned
      witnesses, took part in the program. Standardized questionnaires for mood and
      affect were applied. Results show that the younger witnesses perceive the
      experience of the court proceedings as stressful compared to adults. However,
      they also benefit mostly from the victim support services. Fear and stress were
      successfully alleviated. Qualified victim support interventions may play an
      important role in protecting children and adolescents in the courtroom from
      "secondary victimization".

PMID- 11345583
TI  - [The relationship between psychological stress and the clinical course of
      multiple sclerosis. An update].
AB  - The relationship between psychological stress and the course of MS has been
      investigated in several studies using methods with different qualities. The
      majority of findings indicates that acute short-term stressors have no negative
      consequences. Chronic psychosocial stressors, however, such as interpersonal
      conflicts, loss and complicated bereavement, low perceived social support,
      anxiety and depressive episodes have to be regarded as possible risk factors for
      the development of MS exacerbations. The neuroimmunological findings in MS and
      under various stress conditions are delineated with emphasis on the changes in
      lymphocyte and cytokine networks and evaluated with regard to their possible
      clinical significance. Practical consequences for psychological intervention
      strategies are discussed.

PMID- 11345584
TI  - [Mastery of conflictual relationship patterns in the course of a psychodynamic
      focal therapy].
AB  - Mastery is a psychological construct rooted in the psychodynamic psychotherapy
      research. The Mastery Scale provides a reliable content analytic method to
      measure the mastery of maladaptive interpersonal conflicts. With the help of
      model-sentences verbatim transcripts of relationship episodes are assessed
      regarding to six hierarchical so-called levels: lack of impulse-control,
      introjection and projection of negative emotions, difficulties in understanding
      and cognitive control, interpersonal consciousness, understanding of the self and
      self control. Further, mastery capabilities can be quantified by a mastery score.
      For the first time, the instrument is introduced in German by a study of a rather
      well known successful psychodynamic short-term psychotherapy which previously has
      been investigated with several empirical methods. The results verify the
      possibilities of the Mastery Scale in subtly describing changes in the course of
      a psychotherapy.

PMID- 11345585
TI  - [Pair bonding and attachment. A meta-analysis of 63 studies published between
      1987 and 1997].
AB  - Starting with Hazan and Shaver (1987) [8] a new field of research has been
      opened, couple relationship and attachment, which is attracting increasing
      interest worldwide. METHOD: 63 primary studies, published between 1987 and 1997,
      on partner relationship and adult attachment were systematically content analysed
      with regard to their methodology (samples, designs, methodology of data
      collection with regard to attachment status and to couple relationship) and their
      results (demographic data and sex/gender effects; concordance of attachment
      classifications within couples; correspondence between one partner's AAI and the
      other's CRI; associations between attachment and relationship
      stability/relationship satisfaction/partner related explanations/couple
      interaction/psychophysiological data/sexuality; relationship specific effects;
      interactions of attachment, sex/gender and relationship quality). Conceptual and
      methodological problems with regard to the measurement of adult attachment are
      critically discussed (the two "camps": AAI-researchers and self-report
      questionnaire researchers; categorical versus dimensional assessments; global
      trait or relationship specific construct; conscious or unconscious) and research
      conclusions derived.

PMID- 11345586
TI  - Two novel genes FIND and LIND differentially expressed in deactivated and
      Listeria-infected human macrophages.
AB  - Deactivation of macrophage functions plays an important role in human infectious
      and inflammatory diseases. In this study, differential-display RT-PCR was used to
      analyze the gene expression of human mononuclear phagocytes deactivated with
      interleukin (IL)-4, IL-10, and dexamethasone (DEX), in the absence and presence
      of infection with Listeria monocytogenes (Listeria). Two novel differentially
      expressed mRNA species were discovered: FIND (IL-Four INDuced) was upregulated
      with IL-4 but down-regulated with DEX, and is predicted to code for an M(r)
      53,000 transmembrane protein. LIND (Listeria INDuced) was induced by Listeria
      infection, and is predicted to code for an M(r) 39,000 nuclear or cytoplasmic
      protein containing three coiled-coil domains. In addition, we report several
      novel effects of deactivators and infection on the expression of known genes: (1)
      IL-4 caused pronounced upregulation of ABCG2, coding for an ATP-binding cassette
      transporter highly expressed in the placenta, which mediates multidrug resistance
      of cancer cells, but is otherwise of unknown function; (2) both DEX and IL-4
      downregulated osteopontin, an important factor of host resistance against
      intracellular infections; (3) inhibition of the CC-chemokine I-309 mRNA
      expression by all three deactivators in the presence of Listeria infection, and
      (4) upregulation by Listeria infection of the interferon-stimulated gene ISG20 of
      unknown function, whose product localizes with nuclear dots/PML bodies.

PMID- 11345587
TI  - Distribution of HERV-LTR elements in the 5'-flanking region of HLA-DQB1 and
      association with autoimmunity.
AB  - We established the detailed polymorphism of the 5'-flanking region and the first
      exon of the human leukocyte antigen (HLA)-DQB1 alleles. One hundred and forty
      five Spanish rheumatoid arthritis (RA) patients and 200 healthy voluntary blood
      donors from southern Spain along with 42 B-cell lines were analyzed for the
      presence of the retrovirus-derived long terminal repeats (LTRs) LTR3, LTR5, and
      LTR13. LTR3 positivity was always associated with certain DQB1 alleles, i.e.,
      *0302, *0402, *0601, *0202, and *0305. Sequencing analysis of the 5'-flanking
      region of DQB1*0301, *0303 and *0502 alleles in homozygous B-cell lines showed
      the absence of LTR3 and a massive deletion of 5635 base pairs. The undetected
      deletion in the flanking region of some DQB1 alleles and a lack of stratification
      for HLA typing explain previously reported associations of the LTR3 element with
      RA and type I diabetes (IDDM). LTR5 showed identical distribution to LTR3,
      consistent with a previously suggested LTR3-LTR5 tandem arrangement. LTR13
      positivity was associated with DQB1*0302, *0303, and *0402 alleles. Distributions
      of the LTR elements in all B-cell lines, RA patients, and controls could be
      explained entirely by linkage disequilibrium with DQB1 alleles, independently of
      the haplotypes carrying them. LTR elements are known to regulate gene expression.
      Therefore, a possible involvement of LTR13 in the association of DQB1*0302,
      *0303, and *0402 with IDDM requires further investigation. The sequencing results
      of the DQB1 first exon demonstrated that DQB1*0601 was generated by a
      recombination event between a DR53 and a non-DR53 haplotype. Our results shed new
      light on the phylogeny of the HLA region and the possible contribution of DQB1 to
      susceptibility to autoimmunity.

PMID- 11345588
TI  - Nucleotide sequence analysis of the approximately 35-kb segment containing
      interferon-gamma-inducible mouse proteasome activator genes.
AB  - The proteasome activator PA28 is an interferon-gamma-inducible complex made up of
      two related subunits, named PA28 alpha and PA28 beta, with approximately 50%
      amino acid sequence identity. Accumulated evidence indicates that binding of this
      complex to the 20S proteasome enhances the generation of class I-binding
      peptides. Previously, we showed that the genes coding for PA28 alpha and PA28
      beta, designated Psme1 and Psme2, respectively, are located approximately 6 kb
      apart with their 3' ends pointing toward each other on mouse Chromosome 14. In
      the present study, we sequenced the regions adjacent to Psme1 and Psme2. In a
      contiguous stretch of approximately 35 kb, we identified six genes arranged in
      the following order: Cg10671-like (a gene similar to Drosophila CG10671)-Psme1
      Cgi112 (a ubiquitously expressed gene with no known function)-Psme2-Flj10111 (a
      gene coding for a protein with two RING finger domains)-Isgf3g (an interferon
      gamma-inducible gene coding for an interferon-dependent, positive-acting
      transcription factor 3 gamma). Interestingly, the 3' untranslated region of Psme1
      overlaps with that of Cgi112 by 7 bp. Database analysis indicates that the
      corresponding human genes also overlap by up to 7 bp in their 3' untranslated
      regions. The 5' end of the mouse, but not the human, gene coding for PA28 beta
      undergoes alternative splicing that is predicted to alter the N-terminal amino
      acid sequence. Comparison of the mouse sequence with a human draft sequence
      deposited in the NCBI database revealed that the overall organization of the
      region coding for the interferon-gamma-inducible proteasome activator is
      conserved between human and mouse.

PMID- 11345589
TI  - Cloning of Japanese flounder Paralichthys olivaceus CD3 cDNA and gene, and
      analysis of its expression.
AB  - Two distinct CD3 homologue cDNAs, CD3-1 and CD3-2, were isolated from a Japanese
      flounder leukocyte cDNA library. CD3-1 consisted of 961 bp encoding 178 amino
      acid residues, and CD3-2 consisted of 927 bp encoding 182 amino acid residues.
      The two deduced amino acid sequences had an identity of 95.1%, and neither had N
      linked glycosylation sites. The identities between the Japanese flounder CD3s and
      previously reported CD3s (CD3 epsilon, CD3 gamma, or CD3 delta) of Xenopus
      laevis, chicken, and various mammals were approximately 25%. The Japanese
      flounder CD3s had an extracellular domain, a CXXCXE motif, and an immunoreceptor
      tyrosine-based activation motif (ITAM), each of which are important
      characteristics of CD3 chains. Furthermore, the positions of four cysteine
      residues in the extracellular domain were preserved in both of the Japanese
      flounder CD3s. A phylogenetic tree based on the amino acid sequences confirmed
      that the Japanese flounder CD3s are closer to CD3 epsilon than to CD3 gamma and
      CD3 delta. However, the gene structure of Japanese flounder CD3 is identical to
      the chicken and Xenopus CD3 gamma/delta genes and the mammalian CD3 delta gene.
      Southern blot hybridization and the DNA sequence of the CD3 gene of homocloned
      Japanese flounder indicated that the CD3 gene exists as a single copy. Southern
      blot hybridization also showed the presence of a polymorphic variant of Japanese
      flounder CD3. An RT-PCR analysis detected Japanese flounder CD3 mRNA in several
      organs that contained lymphocytes. The proportion of CD3-positive cells in the
      peripheral blood leukocytes was 34.9%.

PMID- 11345590
TI  - From transcription to cell surface expression, the induction of MHC class II I-A
      alpha by interferon-gamma in macrophages is regulated at different levels.
AB  - Using mouse bone marrow-derived macrophages we determined the role of interferon
      (IFN)-gamma at the different steps in expression of the I-A alpha chain of MHC
      class II molecules, from transcription to the cell surface. Levels of
      transcription, RNA, and protein were low in cells not stimulated with IFN-gamma.
      Treatment with IFN-gamma for 24 or 48 h induced an increase in mRNA levels (7-
      and 12-fold) that did not correlate with the increase in transcription (2.5- and
      2.7-fold). The half-life of mRNA was not modified by IFN-gamma. These data
      suggest a block at the level of translation. In fact, IFN-gamma increased
      ribosome loading, which confirms regulation at the translational level. Treatment
      with IFN-gamma increased protein synthesis (6-fold after 48 h) and level of
      expression at the cell surface (3- and 9-fold after 24 and 48 h, respectively).
      Interestingly, treatment with IFN-gamma also increased the I-A alpha protein half
      life from 2 to 6-7 h. This is the first attempt to determine qualitatively and
      quantitatively the regulation of an inducible gene at all the putative levels of
      control. The data indicate that IFN-gamma plays a critical role in MHC class II
      protein expression in macrophages through the regulation of different steps, from
      transcription to surface expression.

PMID- 11345591
TI  - Genomic organization, chromosomal localization, and 5' upstream region of the
      human DC-STAMP gene.

PMID- 11345592
TI  - MICA sequences 2000.

PMID- 11345593
TI  - Molecular cloning and characterization of the mouse CD163 homologue, a highly
      glucocorticoid-inducible member of the scavenger receptor cysteine-rich family.

PMID- 11345594
TI  - C-509T polymorphism in the TGFB1 gene promoter: impact on Crohn's disease
      susceptibility and clinical course?

PMID- 11345595
TI  - PAProC: a prediction algorithm for proteasomal cleavages available on the WWW.
AB  - The first version of PAProC (Prediction Algorithm for Proteasomal Cleavages) is
      now available to the general public. PAProC is a prediction tool for cleavages by
      human and yeast proteasomes, based on experimental cleavage data. It will be
      particularly useful for immunologists working on antigen processing and the
      prediction of major histocompatibility complex class I molecule (MHC I) ligands
      and cytotoxic T-lymphocyte (CTL) epitopes. Likewise, in cases in which
      proteasomal protein degradation has been indicated in disease, PAProC can be used
      to assess the general cleavability of disease-linked proteins. On its web site
      (http://www.paproc.de), background information and hyperlinks are provided for
      the user (e.g., to SYFPEITHI, the database for the prediction of MHC I ligands).

PMID- 11345596
TI  - Molecular polymorphism of O alleles in five populations of different ethnic
      origins.
AB  - Sequences of exons 6 and 7 of the O allele of the ABO gene were studied in 317
      individuals of the O phenotype from five different ethnic groups (Basques,
      Berbers, Akans from the Ivory Coast, and Amerindians: Cayapas from Ecuador and
      Aymaras from Bolivia). Twenty-one O alleles were characterized, among which 9
      differed from all O alleles reported to date. The nine alleles differed from
      either the O01 allele (four out of nine) or O02 allele (five out of nine) by one
      to three point mutations. The number of different O alleles in population samples
      varied greatly: the highest number (13) was observed in Akans, and the lowest (5)
      in Amerindians. Some rare alleles previously reported by others at low
      frequencies were found with high frequencies in the Akans. The results also
      revealed a decreasing frequency of Ov7 alleles from south to north (Akans,
      Berbers, Basques). Berbers and Basques share two rare alleles, Ov6 and O03, which
      were not encountered in the other populations studied here.

PMID- 11345597
TI  - [Generalized macular rash with palmar-plantar involvement associated with
      lymphadenopathies. Secondary lues].

PMID- 11345599
TI  - [Asymptomatic pulmonary thromboembolism in patients with deep venous thrombosis].

PMID- 11345598
TI  - [A 34-year-old man with lingual tumor. Lingual leishmaniasis in a patient with
      HIV infection].

PMID- 11345600
TI  - [Cardiotoxicity of 5-fluorouracil: ischemia or myocardial toxicity?].

PMID- 11345601
TI  - [Non-cardiogenic acute pulmonary edema and recurrent leukopenia caused by
      hydrochlorothiazide].

PMID- 11345602
TI  - [Multiple organ failure associated with use of ecstasy].

PMID- 11345603
TI  - [Strongyloides stercoralis infestation in patients with chronic obstructive lung
      disease in Vega del Segura (Murcia). 3 case reports].

PMID- 11345604
TI  - [Clinical significance of Strongyloides stercoralis in our environment].

PMID- 11345605
TI  - [Healing with vitamins].

PMID- 11345606
TI  - [Thromboembolism prevention in acute myocardial infarction].
AB  - The objectives were to identify risk factors for vein thromboembolic disease
      (VTD) among patients with acute myocardial infarction (AMI) and to analyse both
      quantitatively and qualitatively the performed thromboembolic prophylaxis. A
      cross-sectional study was carried out with all inpatients at the Coronary Unit at
      our hospital during 1998. The risk factors for thromboembolism included:
      inmobilization (79.2%), heart failure (33.2%) and age over 70 years (31%). VTD
      prophylaxis was performed in 86.9% of the time. Non-fractioned heparin (NFH) and
      low molecular weight heparins (LMWH), mostly nadroparine, were the most commonly
      used drugs at admission and at discharge, respectively. Overdosage and
      underdosage for NFH and LMWH, respectively, were observed. That patients received
      or not VTD prophylaxis was not influenced by thromboembolic risk factors.

PMID- 11345607
TI  - [Community-acquired pneumonia requiring hospital admission. A comparison of the
      clinical management, resource use and prognosis by different medical
      specialties].
AB  - OBJECTIVE: To evaluate whether there are differences regarding therapy, resource
      use and prognosis of inpatients due to community acquired pneumonia (CAP) in
      different clinical departments. METHODS: One-year retrospective study, using the
      discharge abstract, of all patients aged over 7 years admitted to the general
      hospital with the diagnosis of CAP. Comparison of the appropriateness of
      antibiotic therapy, mean hospital stay, use of invasive procedures, intrahospital
      mortality rate, and readmissions between the different clinical departments.
      RESULTS: A total of 511 patients were studied, 154 in Internal Medicine, 197 in
      Pneumology, 107 in Geriatrics and 53 in other departments, with moderate to
      severe underlying disease in 50.8%, severity criteria of CAP in 75%, and
      intrahospital mortality rate of 11.7%. No differences were observed regarding
      mean stay or appropriateness of antibiotic therapy. Invasive procedures were used
      most commonly in the Pneumology Department (12% vs 2%-7.5%; p = 0.001). In the
      Geriatrics Department readmissions were most common (10% vs 1%-4%; p = 0.006) and
      intrahospital mortality rate (19% vs 8.6%-13.2%; p = 0.029) than in the remaining
      departments. Intrahospital mortality was associated with a moderate or severe
      underlying disease, neurologic disease, severity criteria of CAP and ICU
      admission, and readmissions with a moderate or severe underlying disease.
      CONCLUSIONS: There are relevant differences in intrahospital mortality rate and
      readmissions among patients with CAP in the different clinical departments, which
      seem to be associated with the underlying disease and the severity of the CAP.

PMID- 11345608
TI  - [Analysis of avoidable mortality in Valencia Community hospitals].
AB  - Using a list of avoidable mortality (AM) causes as indicators of medical care
      (IMC) according to the Holland classification, a study on AM was conducted in the
      Valencia Community hospitals during 1994 and 1995. A total of 617 patients out of
      106,540 discharges with IMC criteria died (mortality rate: 0.58%). The most
      common causes of AM included hypertension and cerebrovascular disease, with 46%
      of avoidable deaths; maternalperinatal disease, with 36%, and tuberculosis, 7%.
      According to the logistic regression analysis, men had a higher risk of AM than
      women, the age groups at highest risk were those over 50 years and less than 18
      years, and the presence of a higher number of diagnoses was associated with
      increased risk.

PMID- 11345609
TI  - [Study of cobalamin deficiency in gastrectomized and aged subjects].
AB  - OBJECTIVE: The objective of this study were: a) to investigate vitamin B12
      deficiency among and advanced aged, clinically healthy, asymptomatic population,
      presumably with a high prevalence of vitamin B12 deficiency. This deficiency was
      defined as an increase in the MMA/creatinine ratio in urine and/or basal plasma
      HT levels which normalize after the administration of vitamin B12; b) its
      relationship with plasma vitamin B12 levels. SUBJECTS AND METHODS: A total of 45
      subjects were studied, 19 in the Group of Gastrectomized patients, who were
      selected on the basis of an age over 60 years and partial gastrectomy of more
      than five years, and 26 in the Geriatric Group selected in two nursing homes. All
      of them were asymptopatic and "healthy" according to data in the clinical records
      and clinical examination, analytical studies, and none of them was taking any
      drug that might alter results. After basal analytical studies, which included
      B12, folates, metilmalonic acid/creatinine (MMA/creatinine) in urine and total
      plasma homocysteine (TH), i.m. vitamin B12 was administered for 15 days to the
      gastrectomized patients and oral B12 for 28 days with 2.5 mg folic acid for the
      last 14 days to the patients in the Geriatric Group. Basal analytical studies
      were repeated at the end of the study. RESULTS: Basal analytical studies were
      normal with the exception of two subjects with low levels of hemoglobin and 8
      with decreased MCV. Only one subject had decreased serum cobalamines. Nine
      subjects (20%) were identified with increased basal levels of MMA/creatinine
      which normalized after decreasing between 97% and 12% after the administration of
      vitamin B12. TH and MCV also decreased significantly. Basal levels of vitamin B12
      ranged from 244 pg/ml to 483 pg/ml (n = 220 pg/ml-980 pg/ml). CONCLUSIONS:
      Vitamin B12 deficiency, defined as an increase in the MMA/creatinine ratio and TH
      normalized with B12, is highly prevalent among elderly subjects and may occur in
      absence of clinical and/or analytical manifestations. Given the widespread
      recommendation of quantitating MMA and TH for the diagnosis of borderline cases
      of vitamin B12 deficiency, such disturbance may occur in clinically and
      biochemically normal subjects. Thus, a special caution should be exerted, given
      the existing comorbidity in advanced ages, before attributing B12 deficiency to a
      condition which may be the expression of another concomitant condition.

PMID- 11345610
TI  - [Agricultural occupation and strongyloidiasis. A case-control study].
AB  - BACKGROUND: In the last few years, Strongyloides stercoralis has been repeatedly
      recovered from indigenous farmers in the Safor area (Valencia Community). The
      relationship between the different occupational activities, mainly farming, and
      the presence of strongyloidiasis was investigated. PATIENTS AND METHODS: A paired
      case-control study was designed. The investigation was conducted at Oliva Centro
      de Salud, from October 1997 to October 1999. Diagnosis was established when
      Strongyloides stercoralis was observed in any of the three serial fecal samples
      requested when eosinophilia was observed in the hemogram. Controls were persons
      matched by sex and age (+/- 5) years, with no eosinophilia in the hemogram and in
      whom the presence of the parasite was excluded in fecal samples. RESULTS:
      Participants in the study were 47 cases and their respective controls. Each group
      included 39 (83%) men and 8 (17%) women. Forty-five cases (95%) and 42 controls
      (89%) had been born in Safor. Only two cases had travelled to endemic areas.
      Farming was the main activity in 32 (68%) cases and 31 (66%) controls. The only
      occupational activity which showed influence on strongyloidiasis was working in
      ricefields, with an OR of 2.97 (95% CI: 1.16-7.71). Dermatologic symptoms were
      significant for pruritus, OR 7.39 (95% CI: 2.29-27.60). One case with
      hyperinfection and another with larva currens were diagnosed. CONCLUSION: In our
      area, working in ricefields and chronic pruritus are associated with chronic
      strongylodiasis.

PMID- 11345611
TI  - [Therapeutic criteria in hyperuricemia].

PMID- 11345613
TI  - [Heart diseases caused by cytostatic agents].

PMID- 11345612
TI  - [Secondary prevention of opportunistic infections in HIV-infected patients].

PMID- 11345614
TI  - [High-dose chemotherapy in nonhematologic tumors].

PMID- 11345615
TI  - [Proptosis and orbital tumor in an 80-year old woman. Primary orbital
      amyloidosis].

PMID- 11345616
TI  - [Intermittent melena and pancreatic mass in a patient with chronic alcoholism.
      Pseudoaneurysm of the gastroduodenal artery. Chronic pancreatitis of probable
      alcoholic origin].

PMID- 11345617
TI  - [A 22-year-old woman with confusional episodes and hypoglycemia].

PMID- 11345618
TI  - [Perioperative medical complications in orthognathic surgery. Discussion of the
      anesthetic protocol].

PMID- 11345619
TI  - [Unfavorable effects induced by mandibular surgery in Class II malocclusions].
AB  - The sagittal split ramus osteotomy is probably the most frequently used procedure
      for correction of mandibular skeletal dento-facial deformities. In the 30 years
      since the procedure was introduced, a number of complications has been reported:
      unfavorable fracture during surgery, paresthesia or anesthesia and relapse. The
      literature seems to be very poor concerning the esthetical and morphological
      complications of the sagittal split ramus osteotomy; especially when treating
      Class II dento-facial deformity frequently associated with a genioplasty. The
      purpose of this study was to determine and analyze the esthetical complications
      occurring after mandibular surgery in patients with Class II dento-facial
      deformities: Pre-angular notches, Widening of the bi-angular distance, The
      unaesthetic effects of the associated genioplasty, Class III like "dento-facial
      deformities", Plates and screws visibility. Each of those complications has been
      analyzed to find a preventive treatment.

PMID- 11345620
TI  - [Complications of orthognathic surgery. Apropos of a series of 84 patients].
AB  - BACKGROUND: Patients demand satisfactory functional and esthetic results from
      orthognatic surgery. The aim of this study as to assess adverse outcomes after
      orthognatic surgery. PATIENTS AND METHODS: We retrospectively reviewed 84
      patients who underwent maxillary (22.6%), mandibular (29.8%) or bimaxillary
      (38.1%) osteotomy in 1997. We re-examined 76 of these patients at a mean 21
      months follow-up. Data were recorded for the preoperative, early postoperative,
      secondary postoperative and late postoperative periods. RESULTS: Infectious
      complications occurred in 2% of the cases of maxillary surgery. For mandibular
      surgery there were 10.5% infectious complications including 83% that resolved
      spontaneously, 3.5% neurological complications and 1.7% temporomandibular joint
      complications. DISCUSSION: Maxillary osteotomy has proven reliable. Major adverse
      outcome is infrequent but serious. Adverse outcomes in mandibular surgery are
      more common but less problematic.

PMID- 11345621
TI  - [Infectious complications of mandibular osteotomy].
AB  - BACKGROUND: Infection is a rare complication after orthognathic surgery. A rate
      of 1% to 15% has been reported in the literature. We reviewed our experience.
      MATERIAL AND METHODS: We reviewed retrospectively 60 mandibular osteotomies
      performed between 1998 and 1999. There were 41 women and 19 men, mean age 24
      years. All were given antibiotic therapy using cefamandol 1500 mg preoperatively
      then 750 mg every 6 hours peroperatively and cefixime 400 mg/d postoperatively
      for 7 days. Patients were followed for at least 6 months after surgery. RESULTS:
      There were 10 infections (16% of the cases) involving a hematoma in 2 cases,
      adenitis in 1, osteitis on a cortical fragment in 2 and osteitis on implanted
      material in 5. DISCUSSION: We defined infection following orthognathic surgery as
      a collection or purulent fistula with either a high polynuclear count in the
      discharge fluid or a positive culture. Both soft tissue (for example infection of
      a perimandibular hematoma) or bone infections were equally considered. We found
      two types of risk factors: patient-related or procedure-related. Patient-related
      factors included smoking, paradontal status, and dental hygiene. The main
      procedure-related factor was duration of surgery. Measures of prevention include
      extraction of the wisdom teeth, interruption of smoking, preoperative scaling and
      careful dental care, rigorous operative technique, antibiotic therapy.

PMID- 11345622
TI  - [Complications of genioplasty].
AB  - Genioplasty is one of the safest interventions in orthognathic surgery. We
      reviewed a series of 200 cases of genioplasty with or without other osteotomies
      and found 6 complications. We compared our findings with the rare data reported
      in the literature. We were able to distinguish: peroperative complications:
      atypical osteotomy, hemorrhage, soft tissue damage, injury to the mental nerve;
      postoperative complications: neurosensory deficits, hematoma, infection,
      secondary displacement, bone necrosis, mental ptosis, defective ossification,
      dental lesions, paradontal lesions, irregular mandibular contours. We present a
      discussion on means of prevention and treatment of these complications following
      genioplasty.

PMID- 11345623
TI  - [Orthognathic surgery].

PMID- 11345624
TI  - [Peripheral facial paralysis caused by an orthognathically-designed osteotomy in
      a Class III malocclusion].
AB  - Sagittal split ramus osteotomy creates an internal and an external valves. In an
      18-year-old girl with class III dysmorphism, a bone spur on the internal valve
      compressed the facial nerve during the mandibular setback, leading to facial
      palsy after three days. We propose a surgical procedure and discuss short-term
      and long-term outcomes.

PMID- 11345625
TI  - [The management of temporomandibular joint disorders. The role of occlusal
      splints].
AB  - Occlusal appliances are often used for the diagnosis and treatment of pain and
      dysfunction related to the mastication system, despite the lack of a precise
      diagnosis. We reviewed the indications for occlusal appliances, classing them by
      accepted procedures for precise diagnosis. The type of appliance to use for each
      pathological situation is described. Conditions other than those described here
      do not, in the author's opinion, constitute warranted indications for occlusal
      appliances.

PMID- 11345626
TI  - [Writing].

PMID- 11345627
TI  - [The teaching of oral medicine and maxillofacial surgery at the Faculty of
      Medicine in Grenoble].

PMID- 11345628
TI  - [Perioperative medical complications in orthognathic surgery].
AB  - PURPOSE: To describe per and postoperative medical complications. STUDY DESIGN:
      Prospective, observational study. PATIENTS: Between July and December 1999, 59
      patients scheduled for programmed orthognathic surgery were included. METHODS:
      Anaesthetic and surgical procedures were standardised including patient
      information and training of surgical ward' nurses. During perioperative periods
      (in operative and recovery theater and in surgical ward), all the events were
      qualified on an anaesthetic spreadsheet for a qualitative analysis (description
      of events and treatment procedures). RESULTS: Two main complications were
      described 1) one atelectasia due to blood inhalation during the recovery period
      and 2) local sepsis in surgical ward. These two events were medically treated and
      recovered. No need of blood transfusion or stay in ICU were noted. CONCLUSION:
      Anaesthetic and surgical cooperation is associated with poor morbidity of this
      functional surgery performed in young subjects.

PMID- 11345630
TI  - Acute postural adaptations induced by a shoe lift in idiopathic scoliosis
      patients.
AB  - The objective of this study was to identify acute spinal and three-dimensional
      postural adaptations induced by a shoe lift in a population of idiopathic
      scoliosis (IS) patients. Forty-six IS patients (mean age: 12 +/- 2 years) were
      evaluated radiologically and with a stereovideographic system for pelvic
      obliquity. Based on the initial postural and radiological evaluation, a pertinent
      shoe lift height was chosen for each with the result that 12 patients were tested
      with 5-mm (S5) lifts, 20 patients were tested with 10-mm (S10) lifts, and 14
      patients with 15-mm (S15) lifts. The posture for all 46 patients was then re
      evaluated and a spinal radiograph obtained for 14 patients. The implementation of
      a shoe lift independent of the type of curve and amplitude significantly
      decreased the Cobb angle. As expected there was a change in the vertical height
      of the left tibial plateau and greater trochanter that induced a change in pelvic
      tilt. There was also a significant increase in the vertical height of S1 and T1.
      There was a significant change in the left and right iliac bone version, as well
      as a decrease in the difference in version between these two bones. The
      implementation of the shoe lifts also changed the lateral shift of the pelvis. A
      relative change between the shoulders and pelvis for tilt and anteroposterior
      shift was also found to be significant. In conclusion, using a shoe lift resulted
      in acute postural adaptations which specifically affected the spine and the three
      dimensional position and orientation of the pelvis and shoulder girdle.

PMID- 11345629
TI  - Preoperative and early postoperative three-dimensional changes of the rib cage
      after posterior instrumentation in adolescent idiopathic scoliosis.
AB  - Rib cage deformity is an important component of scoliosis, but few authors have
      reported the three-dimensional (3-D) effect of surgical procedures with posterior
      instrumentation systems on the shape of the rib cage. The objective of this
      prospective clinical study was to measure the short-term 3-D changes in the shape
      of the rib cage at the apex of the curve after corrective surgery of adolescent
      idiopathic scoliosis by a posterior approach using a multi rod, hook and screw
      system. The 3-D shape of the spine and rib cage was modelled pre- and
      postoperatively using a 3-D reconstruction technique based on multi-planar
      radiography in a group of 29 adolescents with idiopathic scoliosis. Geometrical
      indices describing the scoliotic deformity of the rib cage were computed from
      these models and were compared pre- and postoperatively using Student's t-tests.
      The frontal spinal curve correction averaged 53% in the frontal plane, while no
      significant change was noted in the sagittal plane. Significant changes were
      noted in the shape of the rib cage: rib hump at the apex and at the adjacent
      lower level were improved (36% and 38%), and small but significant differences
      were detected in rib frontal orientation in the concavity of the curves at the
      apex and adjacent lower rib levels. Multi rod, hook and screw instrumentation
      systems, such as Cotrel-Dubousset instrumentation, are effective in producing
      significant improvements in the 3-D shape of the rib cage, but these changes are
      less important than those observed at the spine level.

PMID- 11345631
TI  - A new MRI technique for imaging scoliosis in the sagittal plane.
AB  - The purpose of the present study was to introduce a new magnetic resonance
      imaging (MRI) procedure showing the whole spine in a coronal and sagittal plane,
      and to study the assessment of sagittal Cobb angle measurements using this
      technique. Prospectively we studied 32 patients (average age 14.8 years) with
      idiopathic scoliosis (mean thoracic Cobb angle 33 degrees on radiograph) and 18
      patients (average age 14.5 years) without scoliosis. The MRI investigation was
      carried out in a standard supine position. The cervical and upper thoracic spine
      and the lower thoracic and lumbar spine were measured on a 1.5-T Gyroscan ACS-NT
      Powertrak 6000 system. An algorithm was developed to combine the results of the
      cranial and caudal scans into a coronal and a sagittal image of the whole spine
      (MR total spine imaging). Measurement of the sagittal Cobb angle conducted ten
      times by four independent investigators revealed an intraobserver variance of 1.6
      degrees and an interobserver variance of 1.8 degrees. In the group with scoliosis
      the mean sagittal Cobb angle from T4 to T12 was 12 degrees (range -3 degrees to
      24 degrees) and in the group without scoliosis 22 degrees (range 16 degrees to 30
      degrees), which was a significant difference. MR total spine imaging makes it
      possible to image scoliosis in the sagittal plane. On these MR projections,
      idiopathic thoracic scoliosis was identified by a reduced sagittal Cobb angle. MR
      total spine imaging would allow monitoring of scoliosis in the sagittal plane,
      which can reveal relevant clinical data without radiation exposure.

PMID- 11345632
TI  - Spine: posture, mobility and pain. A longitudinal study from childhood to
      adolescence.
AB  - A longitudinal study was undertaken to analyse the development of posture and
      spinal mobility during growth and its relationship to low back pain and sports
      activities. A total of 90 children were examined at 5-6 years of age and re
      examined at 15-16. Sagittal configuration and mobility were measured using
      Debrunner's kyphometer. Information about pain and activities was acquired by
      interview with the parents of the 5- to 6-year-olds and by a questionnaire to the
      15- to 16-year-olds. Posture changed significantly during the study period:
      thoracic kyphosis increased by 6 degrees and lumbar lordosis increased by 6
      degrees. The relationship between kyphosis and lordosis was independent of gender
      at age 5-6, but kyphosis in relation to lordosis was significantly lower in girls
      among the 15- to 16-year-olds. The total sagittal mobility of the spine decreased
      significantly during the 10-year study period: in the thoracic spine by as much
      as 27 degrees and in the lumbar spine by 4 degrees. About one-third of the
      children at the age of 15-16 years stated that they had occasional low back pain.
      This complaint was more frequent in those stating they had suffered some type of
      back injury, but low back pain was not related to gender, regular physical
      training, posture or spinal mobility. The results of the study showed that
      kyphosis and lordosis increased and mobility decreased in the 90 children who
      were examined both at age 5-6 and 15-16 years. The relationship between kyphosis
      and lordosis decreased in girls but not in boys. Occasional low back pain was
      reported by 38% of the children at the age of 15-16 years, but back pain was not
      related to posture, spinal mobility or physical activity.

PMID- 11345633
TI  - Topographic relations between the neural and ligamentous structures of the
      lumbosacral junction: in-vitro investigation.
AB  - Transient or persistent alterations in the L5 lumbar nerve root have been
      described as a complication after the reduction of spondylolistheses. In a
      retrospective analysis of our own patients, we observed a higher incidence of
      transient motor and sensomotor deficits after single-sitting anatomic correction
      of May-erding grade IV anterolistheses and spondyloptoses. These findings are
      consistent with those of other authors. The deficits pertained to muscles in the
      innervation range of the L5 nerve root, without there being any evidence of
      intradural root damage or nerve compression. In vitro studies have shown
      distraction and translation of the nerve root to be pathogenetically relevant
      mechanisms, leading to damage during intraoperative reduction. Additional
      alteration of neuronal structures may be caused by ventral parts of the
      iliolumbar ligament complex during the reduction maneuver. In order to reveal
      extradural constrictions of the L5 nerve root that might predispose towards intra
      or perioperative damage, we examined anatomic specimens to determine the course
      and neighboring relationships of the lumbosacral plexus, especially in relation
      to pelvivertebragenic ligamentous connections. In addition to the morphologic
      considerations, we conducted translation tests, which were designed to simulate
      changes in shape and size of the epineural layer, as well as in vitro
      measurements of the resulting pressure on the nerve. In addition to a range of
      variations in the attachment of the iliolumbar ligament complex, which was always
      located dorsally to the nerve roots, we found a ligamentous connection formed by
      connective tissue between the sacrum and the fifth lumbar vertebral body on the
      caudal margin of the ligament apparatus in 14 out of 30 specimens. Its course was
      constantly ventral to the L5 nerve root, which was also adherent to the
      periosteum of the sacrum distal to this constriction in one-fifth of the
      specimens. The average pressure exerted on the nerve root during the distraction
      and translation process was over 30 mmHg in the area of this lumbosacral
      ligamentous connection, at a distance of greater than 20 mm. When the translation
      distance was further increased, perineural fatty tissue was discharged, due to
      increasing perineural pressure.

PMID- 11345634
TI  - Comment on topographic relations of neural and ligamentous structures of the
      lumbosacral junction: in vitro investigation. Spondylolisthesis--no reduction,
      partial reduction or total reduction?

PMID- 11345635
TI  - Comparison of different operative modalities in post-traumatic syringomyelia:
      preliminary report.
AB  - Post-traumatic syringomyelia (PTS) is a relatively rare, but potentially
      disastrous, complication of spinal cord injury. Operative treatment by shunting
      procedures often shows only a short-term improvement, and the rate of recurrence
      of syringomyelia is high, so different treatment modalities have been used in the
      last years. The various results are discussed in this analysis. A prospective
      clinical study was conducted of 30 patients with PTS treated by shunting
      procedures or with pseudomeningocele over a period of 9 years, and followed with
      regular clinical and magnetic resonance imaging examinations. Shunting procedures
      like syringosubarachnoid and syringopleural or -peritoneal shunting showed good
      results only at the first follow-ups. In our department, we perform an artificial
      liquor reservoir at the level of the lesion after opening the spinal pathways and
      arachnoid adhesions at that level. This procedure was performed in 12 patients.
      Five of these had been previously operated by shunting procedures; all of them
      had suffered a recurrence of syringomyelia because of internal occlusion. In the
      group of patients treated by shunting procedures, a neurological improvement was
      be recorded in five, and a steady state in eight. Five patients showed a further
      deterioration. The performance of an artificial liquor reservoir to guarantee a
      free flow of cerebrospinal fluid around the lesion resulted in a neurological
      improvement in ten patients, with two maintaining a steady state. Our experience
      is that shunting procedures often show a neurological improvement only in the
      short term; the rate of recurrence of typical shunting complications is high. The
      performance of a pseudomeningocele is an encouraging new step in the treatment of
      PTS. Further long-term follow-up studies are necessary to assess the benefits of
      this new method.

PMID- 11345636
TI  - Trapped in the neutral zone: another symptom of whiplash-associated disorder?
AB  - Instability of the cervical spine following whiplash trauma has been demonstrated
      in a number of studies. We hypothesized that, in patients with whiplash
      associated disorder, rotation of the head would be accompanied by an earlier
      onset of neck muscle activity to compensate for intrinsic instability. The aim of
      the study was to examine the range of motion (RoM) of the cervical spine and the
      onset and activity of the sternocleidomastoid (SCM) muscles during axial
      rotation, in healthy control subjects and in patients with chronic whiplash
      associated disorder. Forty-eight control subjects (42% male) and 46 patients (33%
      male) with chronic whiplash-associated disorder (symptoms lasting longer than 3
      months) were examined. Cervical axial RoM differed significantly (P = 0.0001)
      between the groups, with the whiplash patients showing lower values (83 degrees
      +/- 30 degrees) than the healthy controls (137 degrees +/- 19 degrees). The
      whiplash patient group showed no evidence of the predicted earlier activation of
      SCM muscles. Many patients never reached the point in the RoM where SCM muscle
      activity rises steeply, as it does in the healthy controls (the 'elastic zone'),
      and their movements remained mostly within the region of low muscle activity (the
      'neutral zone'). The whiplash patients appeared either unable or unwilling to
      drive the cervical spine into this region of high muscle activity, possibly
      because they were restricted by existing pain or fear of pain.

PMID- 11345637
TI  - Slight head extension: does it change the sagittal cervical curve?
AB  - It is commonly believed that slight flexion/extension of the head will reverse
      the cervical lordosis. The goal of the present study was to determine whether
      slight head extension could result in a cervical kyphosis changing into a
      lordosis. Forty consecutive volunteer subjects with a cervical kyphosis and with
      flexion in their resting head position had a neutral lateral cervical radiograph
      followed immediately by a lateral cervical view taken in an extended head
      position to level the bite line. Subjects were patients at a spine clinic in
      Elko, Nevada. All radiographs were digitized. Global and segmental angles of the
      cervical curve were compared for any change in angle due to slight extension of
      the head. The average extension of the head required to level the bite line was
      13.9 degrees. This head extension was not substantially correlated with any
      segmental or global angle of lordosis. Subjects were categorized into those
      requiring slight head extension (0 degree-13.9 degrees) and those requiring a
      significant head extension (> 13.9 degrees). In the slight head extension group,
      the average change in global angle between posterior tangents on C2 and C7 was
      6.9 degrees, and 80% of this change occurred in C1-C4. In the significant head
      extension group, the average change in global angle between posterior tangents on
      C2 and C7 was 11.0 degrees, and the major portion of this change occurred in C1
      C4. Out of 40 subjects, only one subject, who was in the significant head
      extension group and had only a minor segmental kyphosis, changed from kyphosis to
      lordosis. The results show that slight extension of the head does not change a
      reversed cervical curve into a cervical lordosis as measured on lateral cervical
      radiographs. Only small extension angle changes (mean sum = 4.8 degrees) in the
      upper cervical segments (C2-C4) occur in head extension of 14 degrees or less.

PMID- 11345638
TI  - Traumatic intervertebral disc lesion--magnetic resonance imaging as a criterion
      for or against intervertebral fusion.
AB  - Lesions of the intervertebral disc accompanying vertebral fractures are the
      subject of controversy and discussion regarding the extent and manner of surgical
      intervention. The question of when to perform disc resection and intervertebral
      fusion, in particular, has not been answered satisfactorily. In order to evaluate
      short- and medium-term lesions of the discoligamentous complex associated with
      thoracolumbar burst fractures, magnetic resonance images made after stabilisation
      and again after implant removal were compared. Between 1997 and 1998, 20 patients
      who had suffered thoracolumbar burst fractures (AO classification A3 and B1 [26])
      underwent posterior reduction and stabilisation using a Universal Spine System
      (USS, Synthes, Switzerland) titanium internal fixator. The implant was removed
      after an average of 10 months. Magnetic resonance imaging (MRI) scans were
      performed 1 week after both operations, allowing the changes in a total of 40
      intervertebral discs adjacent to the fractured vertebral body to be investigated.
      The analysis was based on signal intensity of the intervertebral disc in T2
      weighted scans and on morphological criteria. A total of 81% of the discs with
      initially normal T2-weighted signal showed the same signal after implant removal;
      5 discs with initially increased signal intensity in T2-weighted scans
      normalised, 5 showed a decrease in intensity and 3 suffered a partial loss of
      signal. Among the 9 discs with initially decreased T2-weighted signal, only one
      had normalised by the time the implant was removed. A total of 86% of the 14
      morphologically intact discs retained their structural integrity. Of the 25 discs
      with minor defects, only one could be considered as intact after implant removal,
      15 remained the same and 9 deteriorated in structure. No disruption of the
      fibrous ring or of the posterior longitudinal ligament was observed, nor was
      there any prolapse of intervertebral discs. When the intervertebral disk is
      intact and has normal morphology and a normal T2-weighted MRI signal, resection
      or fusion of the fracture adjacent discs appears unjustified. In our opinion, the
      results do not support the possibility of predicting degradation in those discs
      that showed an altered T2-weighted signal after the first operation.

PMID- 11345639
TI  - Augmentation of mechanical properties in osteoporotic vertebral bones--a
      biomechanical investigation of vertebroplasty efficacy with different bone
      cements.
AB  - Recent clinical trials have reported favorable early results for transpedicular
      vertebral cement reinforcement of osteoporotic vertebral insufficiencies. There
      is, however, a lack of basic data on the application, safety and biomechanical
      efficacy of materials such as polymethyl-methacrylate (PMMA) and calciumphospate
      (CaP) cements. The present study analyzed 33 vertebral pairs from five human
      cadaver spines. Thirty-nine vertebrae were osteoporotic (bone mineral density <
      0.75 g/cm2), 27 showed nearly normal values. The cranial vertebra of each pair
      was augmented with either PMMA (Palacos E-Flow) or experimental brushite cement
      (EBC), with the caudal vertebra as a control. PMMA and EBC were easy to inject,
      and vertebral fillings of 20-50% were achieved. The maximal possible filling was
      inversely correlated to the bone mineral density (BMD) values. Cement extrusion
      into the spinal canal was observed in 12% of cases. All specimens were subjected
      to axial compression tests in a displacement-controlled mode. From load
      displacement curves, the stiffness, S, and the maximal force before failure,
      Fmax, were determined. Compared with the native control vertebrae, a
      statistically significant increase in vertebral stiffness and Fmax was observed
      by the augmentation. With PMMA the stiffness increased by 174% (P = 0.018) and
      Fmax by 195% (P = 0.001); the corresponding augmentation with EBC was 120% (P =
      0.03) and 113% (P = 0.002). The lower the initial BMD, the more pronounced was
      the augmentation effect. Both PMMA and EBC augmentation reliably and
      significantly raised the stiffness and maximal tolerable force until failure in
      osteoporotic vertebral bodies. In non-porotic specimens, no significant increase
      was achieved.

PMID- 11345640
TI  - Transforming growth factor beta receptor induction in herniated intervertebral
      disc tissue: an immunohistochemical study.
AB  - Transforming growth factor beta (TGF-beta) is a potent inducer of angiogenesis
      and fibrogenesis. There is presently little information about the
      pathophysiological function of TGF-beta in herniated disc tissue. In order to
      analyze the cellular role and activation of TGF-beta after disc herniation we
      immunostained frozen material from 38 disc herniation operations and from eight
      macroscopically normal discs from organ donors. Polyclonal TGF-beta-I, TGF-beta
      II and TGF-beta receptor type II antibodies were used with the avidin biotin
      complex (ABC-) immunoperoxidase method. All the herniated discs were TGF-beta
      immunopositive. Such immunoreactivity was mainly associated with disc cells. In a
      few samples, capillaries were also TGF-beta immunopositive. Immunopositivity was
      similarly observed in the control discs. To analyze possible differences between
      the two groups, we calculated the ratio of immunopositive disc cells. For all
      three antibodies, a statistically significantly (Mann-Whitney test, P = 0.0001)
      higher number of disc cells showed immunopositivity in the herniated discs. The
      increase in TGF-beta receptor immunopositivity suggested induction of TGF-beta
      receptors in herniated discs. Our results support an active regulatory role for
      TGF-beta in disc cell metabolism.

PMID- 11345641
TI  - 1136 whiplash victims who were asked to complete a questionnaire.

PMID- 11345642
TI  - The quality of medical care clinicians offer their patient depends on many
      factors.

PMID- 11345643
TI  - Internal fixation on the lower cervical spine--biomechanics and clinical practice
      of procedures and implants.
AB  - The decision to opt for a particular internal fixation procedure of a traumatized
      unstable lower cervical spine should be based on analysis and implementation of
      scientific and clinical data on the biomechanics of the intact, the unstable and
      the implant-fixed spine. The following recommendations for surgical stabilization
      of the lower cervical spine seem, therefore, to be justified. Firstly, the
      surgical procedure should be to bring about decompression, realignment, and
      stability. Secondly, the anterior approach should be the primary and preferred
      one. With regard to surgical and positioning technique, this access clearly
      involves fewer problems than the posterior approach; if required, unrestricted
      additional cord decompression can take place; implant fixation is technically
      simple, and the fusion is under direct compression, thus allowing optimal fusion
      healing. The awareness of instability and type of implant permits functional
      therapy, above all for the paraplegic patient. Thirdly, for traumatic conditions,
      posterior methods should be reserved for exceptional indications. The restriction
      to this approach is that the anterior column must be intact and a multi-segmental
      fixation must be used. Posterior fixation seems, therefore, to be more
      appropriate for degenerative, rheumatoid or tumorous instabilities than for
      traumatic instabilities. The cerclage wire technique depends on intact osseous
      posterior elements, while after laminectomy only implants fixed with screws can
      create safe stability. The disadvantages of the posterior access for the
      proprioception of the cervical muscles and the subjective symptoms of the patient
      are known and must be taken into account. Fourthly, combined techniques are
      indicated for highly unstable or particularly complex injuries. On the
      cervicothoracic junction, or in cases of Bechterew's disease, the decision is
      justifiably made in favor of this technique, which can be performed as a one
      stage or two-stage operation. Finally, whenever possible, selection of the
      implant should take into account the foreseeable developments in diagnostic
      procedures, and therefore, in view of the modern imaging techniques likely to be
      used in any follow-up examinations required later, the implant chosen should be
      made of titanium.

PMID- 11345644
TI  - Human plasma carboxylesterase and butyrylcholinesterase enzyme activity:
      correlations with SN-38 pharmacokinetics during a prolonged infusion of
      irinotecan.
AB  - PURPOSE: To characterize the relationships between human plasma irinotecan
      carboxylesterase-converting enzyme activity, caboxylesterase-mediated hydrolysis
      of p-nitrophenyl acetate (pNPA), and the butyrylcholinesterase-mediated
      hydrolysis of butyrylthiocholine in human plasma and to test the ability of these
      in vitro tests to predict the variability in SN-38 pharmacokinetics in adult
      patients during a prolonged infusion of irinotecan. METHODS: Individual plasma
      converting enzyme activity was measured in 20 adult cancer patients participating
      in a pharmacokinetic and phase I clinical trial of a prolonged 96-h intravenous
      infusion of irinotecan. The pNPA and butyrylthiocholine hydrolysis in patient
      plasma was also assayed. RESULTS: The irinotecan carboxylesterase-converting
      enzyme in human plasma had a Vmax of 89.9 +/- 22.7 pmol/h per ml plasma and a Km
      of 207 +/- 56 microM (mean +/- SD, n = 3). The mean value of the specific
      activity of this enzyme in 20 adult cancer patients was 10.08 +/- 2.96 pmol/h per
      ml plasma ranging from 5.43 to 15.39 pmol/h per ml. The area-under-the
      concentration-versus time curve (AUC) ratio of SN-38 to irinotecan (AUCSN
      38/AUCCPT-11) was used to assess the relative SN-38 exposure to the active
      metabolite in individual patients. Pharmacokinetic variations in the relative
      exposure to SN-38 did not correlate with the measured carboxylesterase-converting
      enzyme activity nor with plasma butyrylcholinesterase activity in our patient
      population. However, it did correlate with the measured pNPA hydrolysis activity
      in patient plasma (r2 = 0.350, P = 0.0124, n = 18). CONCLUSIONS: Determination of
      patient plasma pNPA hydrolysis activity may have utility in predicting SN-38
      pharmacokinetics during prolonged infusions of irinotecan.

PMID- 11345645
TI  - Plasma pharmacokinetics and tissue distribution of 17-(allylamino)-17
      demethoxygeldanamycin (NSC 330507) in CD2F1 mice1.
AB  - PURPOSE: 17-(Allylamino)-17-demethoxygeldanamycin (17AAG) is a benzoquinone
      ansamycin compound agent that has entered clinical trials. Studies were performed
      in mice to: (1) define the plasma pharmacokinetics, tissue distribution, and
      urinary excretion of 17AAG after i.v. delivery; (2) to define the bioavailability
      of 17AAG after i.p. and oral delivery; and (3) to characterize the concentrations
      of 17AAG metabolites in plasma and tissue. MATERIALS AND METHODS: All studies
      were performed in female CD2F1 mice. Preliminary toxicity studies used 17AAG i.v.
      bolus doses of 20, 40 and 60 mg/kg. Pharmacokinetic studies used i.v. 17AAG doses
      of 60, 40, and 26.67 mg/kg and i.p. and oral doses of 40 mg/kg. The plasma
      concentration versus time data were analyzed by compartmental and
      noncompartmental methods. The concentrations of 17AAG were also determined in
      brain, heart, lung, liver, kidney, spleen, skeletal muscle, and fat. Urinary drug
      excretion was calculated until 24 h after treatment. RESULTS: A 60 mg/kg dose of
      17AAG, in its initial, microdispersed formulation, caused no changes in
      appearance, appetite, waste elimination, or survival of treated animals as
      compared to vehicle-treated controls. Bolus i.v. delivery of 60 mg/kg
      microdispersed 17AAG produced "peak" plasma 17AAG concentrations between 5.8 and
      19.3 micrograms/ml in mice killed 5 min after injection. Sequential reduction of
      the 17AAG dose to 40 and 26.67 mg/kg resulted in "peak" plasma 17AAG
      concentrations between 8.9 and 19.0 micrograms/ml, and 4.8 and 6.1 micrograms/ml,
      respectively. Noncompartmental analysis of the plasma 17AAG concentration versus
      time data showed an increase in AUC from 402 to 625 and 1738 micrograms/ml.min
      when the 17AAG dose increased from 26.67 to 40 and 60 mg/kg, respectively. Across
      the range of doses studied, 17AAG total body clearance varied from 34 to 66
      ml/min per kg. Compartmental modeling of the plasma 17AAG concentration versus
      time data showed that the data were fitted best by a two-compartment, open,
      linear model. In each study, substantial concentrations of a material,
      subsequently identified as 17-(amino)-17-demethoxygeldanamycin (17AG), were
      measured in plasma. A subsequent, lyophilized formulation of 17AAG proved
      excessively toxic when delivered i.v. at 60 mg/kg. A repeat i.v. study using a 40
      mg/kg dose of this new formulation produced peak plasma 17AAG concentrations of
      20.2-38.4 micrograms/ml, and a 17AAG AUC of 912 micrograms/ml.min, which was
      approximately 50% greater than the AUC produced by a 40 mg/kg dose of
      microdispersed 17AAG. The bioavailabilities of 17AAG after i.p. and oral delivery
      were 99% and 24%, respectively. Minimal amounts of 17AAG and 17AG were detected
      in the urine. After i.v. bolus delivery to mice, 17AAG distributed rapidly to all
      tissues, except the brain. Substantial concentrations of 17AG were measured in
      each tissue. CONCLUSIONS: 17AAG has excellent bioavailability when given i.p. but
      only modest bioavailability when given orally and is metabolized to 17AG and
      other metabolites when given i.v., i.p., or orally. 17AAG is widely distributed
      to tissues. These pharmacokinetic data generated have proven relevant to the
      design of recently initiated clinical trials of 17AAG and could be useful in
      their interpretation.

PMID- 11345646
TI  - Cytocidal effect and DNA damage of nedaplatin in vitro by simulating
      pharmacokinetic parameters.
AB  - PURPOSE: The pharmacodynamic effects of cis-diammine(glycolato)platinum
      (nedaplatin, 254-S) in vitro have been reported, but the dosage and exposure time
      in vitro have not always been based on clinical observations of the drug's
      actions in vivo. Regardless of the actual exposure conditions used, the effect of
      cell-cycle nonspecific anticancer agents such as nedaplatin is believed to depend
      on the area under the drug concentration-time curve (AUC). In this study, we
      evaluated the pharmacodynamics of nedaplatin in vitro, especially in relation to
      its AUC dependency, in terms of cell survival and DNA crosslinking. METHODS: BG-1
      human ovarian cancer cells were treated with various concentrations of nedaplatin
      to simulate the pharmacokinetics of administration in a clinical setting. The BG
      1 cells were exposed to nedaplatin dissolved in medium containing serum using
      constant concentration conditions, either high (maximum 7.69 mg/l) or low
      (average 1.33 mg/l). These concentrations were based on doses used in clinical
      studies. We then adjusted the exposure conditions in vitro to simulate the
      elimination of the drug from serum in vivo as follows: T1/2 alpha 1.20 h and T1/2
      beta 2.70 h. The AUC values were set at 4, 8, 16, 25 and 40 mg.h/l for all
      exposure conditions. A colony-formation assay for the surviving fraction and an
      alkaline-elution assay for DNA crosslink measurement were done for the
      pharmacodynamic evaluation with comparison on the basis of the AUC value.
      RESULTS: Exposure to a low concentration for a long time was the most effective
      of the exposure conditions at the same AUC value. The greater the AUC value, the
      higher the crosslink index under all exposure conditions. This index tended to
      increase particularly after exposure to the low concentration. The natural
      logarithm of the surviving fraction (Y') was a linear function of the crosslink
      index regardless of the drug-exposure condition: ln(Y') = -87.2x + ln(5.79), R2 =
      0.89. The threshold cytocidal effect was associated with a crosslink index of
      0.02. CONCLUSION: There was a strong correlation between the cytocidal effect of
      nedaplatin and DNA crosslink formation. The cytocidal effect and DNA crosslinking
      in vitro depended on the exposure conditions used to define the AUC. Therefore, a
      new pharmacokinetic-pharmacodynamic model for nedaplatin must be constructed to
      investigate the most effective administration procedure in vivo.

PMID- 11345647
TI  - Pharmacokinetic modeling of paclitaxel encapsulation in Cremophor EL micelles.
AB  - Nonlinear disposition of paclitaxel (Taxol) in cancer patients has been described
      in several studies, but the underlying mechanism is still a matter of
      speculation. Previously, we have shown in vitro that the paclitaxel formulation
      vehicle, Cremophor EL (CrEL), alters the blood distribution of paclitaxel as a
      result of entrapment of the compound in circulating CrEL micelles, thereby
      reducing the free drug fraction available for cellular partitioning. Based on
      these findings, we prospectively re-evaluated the linearity of paclitaxel
      disposition in patients using whole blood and plasma analysis, and sought to
      define a new pharmacokinetic model to describe the data. Seven patients with
      solid tumors were treated with paclitaxel infused over 3 h, each at consecutive 3
      weekly dose levels of 225, 175 and 135 mg/m2 (CrEL dose level, 18.8, 14.6, and
      11.3 ml/m2, respectively). Patient samples were collected up to 24 h after the
      start of infusion, and analyzed by high-performance liquid chromatography.
      Paclitaxel peak levels and areas under the curve in whole blood increased
      linearly with dose, whereas plasma levels showed substantial deviation from
      linearity. This was shown to be caused by a CrEL concentration-dependent decrease
      in paclitaxel uptake in blood cells, as reflected by the blood:plasma
      concentration ratios which altered significantly from 0.83 +/- 0.11 (at 135
      mg/m2) to 0.68 +/- 0.07 (at 225 mg/m2). It is concluded that the nonlinear
      disposition of paclitaxel is related to paclitaxel dose-related levels of the
      formulation vehicle CrEL, leading to a disproportionate drug accumulation in the
      plasma fraction. The pharmacokinetic model developed accurately described the
      data, and will help guide future development and refinement of clinical
      protocols, especially in defining the exposure measure best linked to paclitaxel
      effects and toxicities.

PMID- 11345648
TI  - In vitro and in vivo kinetic interactions of the antitumour agent 5,6
      dimethylxanthenone-4-acetic acid with thalidomide and diclofenac.
AB  - BACKGROUND: Previous studies have demonstrated that coadministration of L
      thalidomide with the novel antitumour agent 5,6-dimethylxanthenone-4-acetic acid
      (DMXAA) results in an increased area under the plasma concentration-time curve
      (AUC) of DMXAA, suggesting an explanation for the observed increase in the
      antitumour activity. The aims of this study were to investigate the effects of L
      thalidomide on the in vitro metabolism of DMXAA in mouse and human liver
      microsomes using diclofenac as positive control, to examine the effects of L
      thalidomide and diclofenac on the plasma protein binding of DMXAA in vitro, and
      to investigate whether the in vivo interactions can be predicted from in vitro
      data, particularly in humans. METHODS: Mouse and human liver microsomes were used
      to investigate the effects of L-thalidomide and diclofenac on DMXAA metabolism.
      The resulting in vitro data were extrapolated to predict in vivo changes in
      DMXAA, which were then compared with the results of in vivo mouse pharmacokinetic
      interaction studies. The protein binding of DMXAA in mouse and human plasma was
      determined using ultrafiltration followed by HPLC. RESULTS: Diclofenac at 100
      microM caused significant inhibition of glucuronidation (> 70%) and 6
      methylhydroxylation (> 54%) of DMXAA in mouse and human liver microsomes. In vivo
      diclofenac (100 mg/kg i.p.) resulted in a 24% and 31% increase in the plasma
      DMXAA AUC, and a threefold increase in T1/2 (P < 0.05) in male and female mice,
      respectively. In contrast, L-thalidomide at 100 microM had no inhibitory effect
      on DMXAA metabolism in vitro in either species, except for a decrease of about
      25% in 6-methylhydroxylation in mice. L-Thalidomide at 500 microM resulted in
      further significant decreases in 6-methylhydroxylation in mice (30-60%) and human
      (30%) microsomes. Coadministration of L-thalidomide in male mice resulted in a
      23% increase in DMXAA AUC and a twofold increase in T1/2 (P < 0.05). Neither L
      thalidomide nor diclofenac at 50 or 500 microM had any significant effect on the
      in vitro plasma protein binding of DMXAA (500 microM) in mouse or human plasma.
      Based on our in vitro inhibition studies, we predicted a 20% increase in DMXAA
      AUC in mice with concomitant diclofenac, but little or no effect (< 5%) with L
      thalidomide. CONCLUSION: Both L-thalidomide and diclofenac increased the plasma
      DMXAA AUC in mice. In the case of diclofenac, this appeared to be due to direct
      competitive inhibition of DMXAA metabolism, but this mechanism does not appear to
      be appropriate for L-thalidomide. From the in vitro human inhibition studies, it
      appears unlikely that concurrent diclofenac will cause an increase in the plasma
      AUC of DMXAA in patients. However, the effect of L-thalidomide on DMXAA could not
      be readily predicted from the in vitro data. Our study demonstrated that a
      predictive model based on direct inhibition of metabolism is appropriate for
      diclofenac-DMXAA interactions, but is inappropriate for the prediction of L
      thalidomide-DMXAA interactions in mice and humans in vivo.

PMID- 11345649
TI  - Continuous infusion prochlorperazine: pharmacokinetics, antiemetic efficacy, and
      feasibility of high-dose therapy.
AB  - PURPOSE: The purpose of these sequential phase I studies was to evaluate the
      antiemetic efficacy and pharmacokinetics of high-dose continuous infusion
      prochlorperazine. METHODS: A total of 52 patients with advanced cancer were
      treated in two sequential phase I studies utilizing high-dose prochlorperazine.
      In study 1, designed to investigate the antiemetic effects of dose-intensive
      prochlorperazine, various cisplatin-based multiagent chemotherapeutic regimens
      were administered in combination with escalating doses of prochlorperazine. In
      study 2, a fixed dose of cisplatin (60 mg/m2) was administered over 24 h as a
      continuous intravenous infusion in combination with infusional high-dose
      prochlorperazine. Antiemetic efficacy in the first trial was assessed in terms of
      the number of episodes of nausea, retching, and/or emesis during the 24 h
      following cisplatin administration. The pharmacokinetics of high-dose
      prochlorperazine were evaluated in eight patients treated in study 2 at the two
      dose levels below those at which dose-limiting toxicity was noted. RESULTS: The
      maximally tolerated dose of prochlorperazine in combination with cisplatin (60
      mg/m2 administered as a continuous infusion over 24 h) was 24 mg/h. The dose
      limiting toxicity was grade 4 agitation and confusion noted in one patient
      treated at 26 mg/h. This patient died 3 days following cessation of chemotherapy
      due to the toxicity of the regimen in combination with the debilitating pulmonary
      effects of the disease. The mean end of infusion prochlorperazine level at the 24
      mg/h dose level was 1.1 microM, a concentration previously reported to be
      consistent with the reversal of the multidrug resistance phenotype. Two partial
      responses were observed in study 2. CONCLUSIONS: We conclude that the antiemetic
      efficacy of high-dose infusional prochlorperazine does not appear to be improved
      over more convenient bolus administration. However, prochlorperazine levels
      consistent with those required in vitro for drug resistance reversal are
      attainable within the dose range having a tolerable toxicity profile.

PMID- 11345650
TI  - A phase I trial of amsalog (CI-921) administered by intravenous infusion using a
      5-day schedule.
AB  - PURPOSE: Amsalog, a derivative of 9-aminoacridine, is an inhibitor of
      topoisomerase II. Early studies of intravenous amsalog administered either once
      weekly, or daily for 3 days repeated every 3 weeks, showed that myelosuppression
      is the dose-limiting toxicity (DLT). Phase II studies showed only limited
      activity in breast, head and neck, and non-small-cell lung cancer. The activity
      of other topoisomerase inhibitors is schedule-dependent. We therefore performed a
      phase I study to evaluate the use of amsalog on a more prolonged schedule.
      METHODS: A group of 19 patients with refractory malignancies were treated in six
      cohorts using 2-h infusions of amsalog daily for 5 days, repeated every 3 weeks.
      RESULTS: Myelosuppression was seen as DLT at 200 mg/m2 per day. Other toxicities
      included nausea and vomiting, fatigue, and, when administered via a peripheral
      venous line, severe phlebitis necessitating administration via an indwelling
      central venous catheter for doses greater than 100 mg/m2. Pharmacokinetic studies
      showed a linear relationship between Cmax and AUC, and dose. The terminal half
      life was 2 h, consistent with previous studies. CONCLUSION: We conclude that
      amsalog can be safely given on a 5-day schedule every 3 weeks at doses up to 200
      mg/m2. The dose recommended for further studies is 180 mg/m2 per day for 5 days
      repeated every 3 weeks. However, in view of the phlebitis, which necessitated the
      use of central venous catheters for administration, other routes of
      administration, for example oral formulations, should be explored.

PMID- 11345651
TI  - The enhancement of riboflavin-mediated photo-oxidation of doxorubicin by
      histidine and urocanic acid.
AB  - PURPOSE: Previously we have shown that doxorubicin (Adriamycin, ADR) can be
      inactivated by light-excited riboflavin. The inactivation of the drug results
      from its direct oxidation by the excited triplet riboflavin in a type I
      photosensitization reaction, and 3-methoxysalicyclic acid is an ADR breakdown
      product. In the present study, we investigated the enhancement of this process by
      histidine and some other imidazole analogs. METHODS: ADR solutions containing
      various concentrations of riboflavin and other agents were exposed to 365 nm
      light for various time periods and then the absorbance spectrum of ADR was
      measured by a double beam spectrophotometer. These measurement were used to
      calculate the half-time of the ADR degradation process. The degraded ADR
      solutions were analyzed by HPLC. RESULTS: The rate of bleaching of ADR by light
      excited riboflavin was enhanced in the presence of histidine in a concentration
      dependent manner. This enhancement was more pronounced at higher riboflavin
      concentrations. Histidine also enhanced the riboflavin-mediated photobleaching of
      N,N-dimethyl-4-nitrosoaniline (RNO), a compound known to be resistant to
      oxidation by singlet oxygen but sensitive to oxidation by the trans-annular
      peroxide of histidine. RNO was found to block the histidine enhancement of the
      riboflavin-mediated photobleaching of ADR in a competitive manner. Among the
      imidazole analogs of histidine tested, urocanic acid was found to be the most
      efficient enhancer of the riboflavin-mediated photobleaching of ADR. Superoxide
      anion radicals which retard the oxidation of ADR were quenched by urocanic acid
      but not by histidine. It was shown that the oxidation of ADR by the trans-annular
      peroxide of histidine resulted in the formation of 3-methoxysalicylic acid.
      CONCLUSIONS: In contrast to singlet oxygen, the trans-annular peroxide, formed by
      the interaction of histidine and the singlet oxygen produced by photoexcited
      riboflavin, is an efficient oxidizer of ADR. The enhancement of the riboflavin
      mediated photobleaching of ADR by histidine analogs depends on the rate of their
      conversion to a trans-annular peroxide and on the efficiency of these products in
      oxidizing ADR. However, for some analogs of histidine, as shown for urocanic
      acid, other mechanisms could also be involved. The presence of urocanic acid in
      the skin suggests that significant degradation of ADR could occur in the presence
      of biologically relevant concentrations of riboflavin if patients treated with
      ADR are exposed to sunlight. The finding that histidine also enhanced the
      degradation of ADR to 3-methoxysalicylic acid, suggests that the process of ADR
      oxidation by the trans-annular peroxides is similar to the direct oxidation of
      ADR by excited triplet riboflavin.

PMID- 11345652
TI  - A phase I and pharmacokinetic study of bi-daily dosing of oral paclitaxel in
      combination with cyclosporin A.
AB  - PURPOSE: To investigate dose escalation of bi-daily (b.i.d.) oral paclitaxel in
      combination with cyclosporin A in order to improve and prolong the systemic
      exposure to paclitaxel and to explore the maximum tolerated dose and dose
      limiting toxicity (DLT) of this combination. PATIENTS AND METHODS: A total of 15
      patients received during course 1 two doses of oral paclitaxel (2 x 60, 2 x 90, 2
      x 120, or 2 x 160 mg/m2) 7 h apart in combination with 15 mg/kg of cyclosporin A,
      co-administered to enhance the absorption of paclitaxel. During subsequent
      courses, patients received 3-weekly intravenous paclitaxel at a dose of 175 mg/m2
      as a 3-h infusion. RESULTS: Toxicities observed following b.i.d. dosing of oral
      paclitaxel were generally mild and included toxicities common to paclitaxel
      administration and mild gastrointestinal toxicities such as nausea, vomiting, and
      diarrhea, which occurred more often at the higher dose levels. Dose escalation of
      b.i.d. oral paclitaxel from 2 x 60 to 2 x 160 mg/m2 did not result in a
      significant increase in the area under the plasma concentration-time curve (AUC)
      of paclitaxel. The AUC after doses of 2 x 60, 90, 120, and 160 mg/m2 were 3.77 +/
      2.70, 4.57 +/- 2.43, 3.62 +/- 1.58, and 8.58 +/- 7.87 microM.h, respectively.
      The AUC achieved after intravenous administration of paclitaxel 175 mg/m2 was
      17.95 +/- 3.94 microM.h. CONCLUSION: Dose increment of paclitaxel did not result
      in a significant additional increase in the AUC values of the drug. Dose
      escalation of the b.i.d. dosing regimen was therefore not continued up to DLT. As
      b.i.d. dosing appeared to result in higher AUC values compared with single-dose
      administration (data which we have published previously), we recommend b.i.d.
      dosing of oral paclitaxel for future studies. Although pharmacokinetic data are
      difficult to interpret, due to the limited number of patients at each dose level
      and the large interpatient variability, we recommend the dose level of 2 x 90
      mg/m2 for further investigation, as this dose level showed the highest systemic
      exposure to paclitaxel combined with good safety.

PMID- 11345653
TI  - PNU-159548, a novel cytotoxic antitumor agent with a low cardiotoxic potential.
AB  - PURPOSE: PNU-159548 (4-demethoxy-3'-deamino-3'aziridinyl-4'-methylsulphonyl
      daunorubicin), a derivative of the anticancer idarubicin, has a broad spectrum of
      antitumoral activity in vitro and in vivo attributable to its DNA intercalating
      and alkylating properties. The present study was conducted to determine the
      cardiotoxic activity of PNU-159548 relative to doxorubicin in a chronic rat model
      sensitive to anthracycline-induced cardiomyopathy. METHODS: Young adult male rats
      were allocated to the following treatment groups: group 1, PNU-159548 vehicle
      control (colloidal dispersion); group 2, doxorubicin control (saline); groups 3,
      4, 5, 6, and 7, PNU-159548 at 0.12, 0.25, 0.50, 0.75, and 1.0 mg/kg,
      respectively; and group 8, 1.0 mg/kg doxorubicin. Treatments were administered
      intravenously once weekly for 4 weeks (first sacrifice time) or for 7 weeks (rats
      killed at weeks 8, 12, 22, 27, or 35). Body weights, organ weights, serum
      chemistry, hematology, serum troponin-T, and cardiac histopathology were followed
      throughout the study. RESULTS: Doxorubicin caused irreversible cardiomyopathy
      evident at week 4 in some rats and progressing in severity in all rats by week 8.
      There were also marked myelotoxicity, increased liver and kidney weights,
      testicular atrophy, and about 20% mortality by week 27 in doxorubicin-treated
      rats. The deaths were attributed to cardiomyopathy and/or nephropathy. PNU-159548
      caused a dose-dependent myelotoxicity, with the dose of 0.5 mg/kg per week being
      equimyelotoxic to 1.0 mg/kg per week doxorubicin. PNU-159548 also caused an
      increase in liver weight that was reversible and a non-reversible testicular
      atrophy but, unlike doxorubicin, had no effect on kidney weight. At
      equimyelotoxic doses, the cardiotoxicity caused by PNU-159548, expressed as the
      mean total score, was less than one-twentieth of that induced by doxorubicin, and
      much less than that predicted on the basis of its content of idarubicin, which is
      in turn markedly less cardiotoxic than doxorubicin. CONCLUSIONS: The novel
      cytotoxic antitumor derivative, PNU-159548, is significantly less cardiotoxic
      than doxorubicin at equimyelosuppressive doses. The combination of intercalating
      and alkylating activities within the same molecule without the cardiotoxic side
      effects of anthracyclines makes PNU-159548 an excellent candidate for clinical
      development in oncology.

PMID- 11345654
TI  - Effects of single or split exposure of leukemic cells to temozolomide, combined
      with poly(ADP-ribose) polymerase inhibitors on cell growth, chromosomal
      aberrations and base excision repair components.
AB  - PURPOSE: To evaluate the antitumor activity of single versus split exposure of
      neoplastic cells to temozolomide (TZM) and poly(ADP-ribose) polymerase (PARP)
      inhibitor. METHODS: A leukemic Jurkat cell line and freshly isolated leukemic
      blasts were used. Jurkat cells are resistant to O6-methylguanine damage induced
      by TZM due to high levels of O6-alkylguanine-DNA alkyltransferase and to a
      functional defect in the mismatch repair system. Cells were treated with 3
      aminobenzamide or with NU1025 to inhibit PARP activity. TZM was added to cell
      cultures immediately after PARP inhibitors. The concentrations of TZM used were
      62.5 microM (corresponding to the peak plasma concentration in patients) or 125
      microM. TREATMENT DESIGN: Cells were treated with 125 microM TZM plus PARP
      inhibitors (single exposure), or twice with 62.5 microM TZM plus PARP inhibitors
      with an interval of 24 h between treatments (split exposure). Tumor cell growth,
      clastogenicity and base excision repair gene transcripts or enzymatic activity
      were evaluated. RESULTS: The split exposure of Jurkat cells to TZM induced more
      pronounced and persistent growth inhibition and comparable chromosome damage in
      comparison with the single exposure. In addition, PARP inhibitors potentiated the
      cytotoxic effects induced by repeated treatment with TZM in fresh leukemic
      blasts. A marked decrease in X-ray repair cross-complementing 1 transcript and
      methylpurine glycosylase (MPG) transcript was detected in Jurkat cells subjected
      to the split exposure. In this case, a significant reduction in the corresponding
      enzymatic activity was also observed. CONCLUSIONS: Cytotoxicity induced by TZM
      and PARP inhibitors can be improved by a fractionated modality of drug treatment.
      The reduction in MPG transcript and function would presumably contribute to an
      increase in cell susceptibility to DNA damage induced by the methylating agent
      and PARP inhibitors.

PMID- 11345656
TI  - Critical realism and health promotion: effective practice needs an effective
      theory.

PMID- 11345655
TI  - Carboplatin AUC8 in combination with etoposide and bleomycin in the treatment of
      intermediate and poor-risk metastatic germ cell tumours: a phase II study.
AB  - PURPOSE: Carboplatin has demonstrated significantly poorer response rates in non
      seminomatous germ cell tumours. A phase II study of higher than standard doses of
      carboplatin was conducted because of suspicion that the poorer response might
      have been due to suboptimal dosing. PATIENTS AND METHODS: A group of 19 patients
      with advanced germ cell tumours (International Germ Cell Cancer Collaborative
      Group intermediate and poor prognosis) were treated with carboplatin at an AUC of
      8 mg/ml.min (using Calvert's formula) on day 1, etoposide 120 mg/m2 days 1-3 and
      bleomycin 60,000 U over 2 days (EBCa). Treatment was repeated every 3 weeks and a
      maximum of four courses was given. RESULTS: Of the 19 patients, 7 (37%) achieved
      complete remission, of whom 6 (32%) remained long-term progression-free. Post
      chemotherapy surgery and further chemotherapy salvaged an additional 26%, leading
      to an overall disease-free survival rate of 58%. No relationship between outcome
      and degree of myelosuppression could be established. CONCLUSION: Dose-escalated
      carboplatin in combination, although feasible, did not improve the results and
      led to poorer results than those expected with cisplatin-based therapy. There is
      no evidence that the patients relapsing following this were easier to salvage.
      Further investigation of this regimen cannot be recommended.

PMID- 11345657
TI  - The benefits of anthropological approaches for health promotion research and
      practice.
AB  - In recent years health education practitioners have been looking for ways to
      extend the social psychological analysis of human behavior with approaches that
      focus on the cultural and social context of human behavior. In this article the
      value of the 'thick description' approach, borrowed from anthropology, is
      explored by examples from the Caribbean and South Africa. It demonstrates that an
      anthropological approach has much to offer as a basis for sound interventions for
      understanding human behavior. However, although an anthropological approach
      offers valuable starting points for interventions, its broad scope exceeds the
      traditional goals of health education (changing health beliefs, health
      counseling). Interventions will not aim at informing individuals, but at
      improving cultures. They may concern the change of basic cultural and social
      structures such as gender roles. To limit the risk of ethnocentrism, adequate
      ways need to be developed to make optimal use of the information thick
      description offers, while avoiding ethnocentrism. The article ends with a
      discussion concerning the assets of a dialogical approach towards health
      promotion. A dialogue between health promoters and their target population may
      help solve the problem of ethnocentrism in broadly scoped interventions.

PMID- 11345658
TI  - Smoking and symbolism: children, communication and cigarettes.
AB  - Health promotion, with its concern with empowerment and autonomy, must recognize
      the agency of its target population. Based on 85 in-depth interviews with 10- to
      11-year-old children throughout Northern Ireland, this paper argues that it is
      necessary to focus on the social relations of children if we are to understand
      and prevent childhood smoking. Addressing the complex issue of childhood agency,
      it is argued that regardless of various restrictions to their choices, children
      can act intentionally in constructing their identities. Instead of viewing the
      smoking children as communicating with the adult world, we focus on smoking as
      negotiation of status within the children's culture. Such negotiations utilize
      symbolism derived from and shared with the 'adult world'. It is important that
      those analyzing children's lives understand children's ideas and behaviour on
      their own terms. We must make sure that the very concepts in which the children's
      experiences are put are appropriate ones. It is suggested that the metaphor 'rite
      of passage' and terminology such as peer 'pressure' versus adult 'influence',
      commonly used to analyse the children's smoking behaviour, may actually conceal
      important aspects of childhood agency.

PMID- 11345659
TI  - Smoking amongst UK Bangladeshi adolescents aged 14-15.
AB  - This paper reports on an investigation into smoking amongst 14- to 15-year-old
      Bangladeshis living in an UK inner city locality. A survey using self-completion
      questionnaires was undertaken in conjunction with focus group discussions. The
      survey of 316 Bangladeshi adolescents was conducted to determine smoking
      prevalence. Regular smoking was more common amongst Bangladeshi males (39%) than
      amongst Bangladeshi females (11%). Thirty-one people (17 females and 14 males)
      took part in seven focus groups (four female and three male) which were conducted
      in schools (six) and youth clubs (one). Focus group discussions were conducted to
      examine what smoking means to Bangladeshi teenagers and factors which influence
      why they do or do not smoke. Differences between what smoking means to
      Bangladeshi females and males are identified which arise from perceived social
      norms and cultural values, and greatly influence smoking uptake. However, many of
      the reasons why Bangladeshi adolescents continue to smoke, stop smoking or never
      smoke appear similar to those identified in other studies with largely white
      adolescents. Factors underpinning adolescent choices together with the
      implications of the study findings for the development of smoking prevention
      initiatives for inner city Bangladeshi teenagers are discussed.

PMID- 11345660
TI  - Predictors of intention to adhere to physiotherapy among women with urinary
      incontinence.
AB  - During the last decade, pelvic floor muscle exercise (PFME) therapy has proved
      its short-term efficacy among women with urinary incontinence. Long-term success
      with PFME therapy is hampered by non-adherence. So far, specific knowledge on
      determinants of adherence behavior has been scarce. A cross-sectional study was
      conducted to elucidate the relative importance of determinants of the intention
      to adhere to PFME therapy in women with urinary incontinence. Based on behavioral
      theories, literature research and interviews, a questionnaire measuring
      determinants of the intention to adhere to PFME therapy was developed. In total,
      129 women, aged 17 years or over, with symptoms of urinary incontinence,
      completed this questionnaire. Multiple regression analysis with backward
      elimination was carried out to identify determinants that predict intention.
      Significant predictors of the intention to adhere to PFME therapy were the amount
      to urinary loss per wet episode and women's perception of their ability to do the
      exercises as recommended under various circumstances. Building self-efficacy
      might be a good starting point for health education interventions aiming to
      promote adherence to PFME therapy, which can be used by physiotherapists and
      general practitioners.

PMID- 11345661
TI  - Child-reported family and peer influences on fruit, juice and vegetable
      consumption: reliability and validity of measures.
AB  - Family, peers and other environmental factors are likely to influence children's
      dietary behavior but few measures of these phenomena exist. Questionnaires to
      measure family and peer influences on children's fruit, juice and vegetable (FJV)
      consumption were developed and pilot tested with an ethnically diverse group of
      Grade 4-6 children. Principal components analyses revealed subscales with
      acceptable internal consistencies that measured parent and peer FJV modeling,
      normative beliefs, normative expectations, perceived peer FJV norms, supportive
      and permissive parenting practices, food rules, permissive eating, and child food
      preparation. Internal consistencies were adequate to high, but test-re-test
      correlations often were low. Children also completed questionnaires on FJV
      availability and accessibility in the home, and food records for 2 days in the
      classroom. Parental modeling, peer normative beliefs and FV availability were
      significantly correlated with FJV consumption. Further research with these scales
      is warranted.

PMID- 11345662
TI  - Health behavior-based selection into educational tracks starts in early
      adolescence.
AB  - Health behaviors and educational tracks of an individual are here presumed to
      have a strengthening influence on each other during the developmental process,
      through which individuals gradually reach their adult health and social position.
      This longitudinal study of a Finnish nationally representative sample of 12 year
      olds born in 1970 (N = 1009) examined the associations of health behaviors at
      ages 12 and 14 with educational track at age 16. The dependent variable,
      educational track, classified the respondents into five successive categories,
      thought to predict their adult social position. Selection into different
      educational tracks according to health behaviors was obvious already at age 12,
      when frequency of tooth brushing, consumption of sweets, coffee drinking and
      level of participation in physical exercise predicted educational track
      independently of sociodemographic background. At age 14, the independent
      predictors were smoking, frequency of tooth brushing and coffee drinking. At both
      ages, sociodemographic factors had independent associations with educational
      track. It seems that certain health-related behaviors in early adolescence are
      indicators of a person's possibilities to benefit from a country's educational
      supply. Both sociodemographic background and health-related behaviors influence
      the process of selection into educational tracks leading to social position and
      health in adulthood.

PMID- 11345663
TI  - Principles in practice: reflections on a 'postpositivist' approach to evaluation
      research.
AB  - User participation is currently seen as an ethically appropriate way to proceed
      when researching disadvantaged groups and it is encouraged by funding agencies.
      However, the literature rarely discusses the methodological and practical
      implications for researchers attempting to incorporate user participation into
      evaluation studies which are informed from an epistemologically opposed
      (positivist) research paradigm. The paper explores this issue by drawing on the
      evaluation of a community-based smoking intervention to describe and reflect upon
      the recruitment, training and employment of local residents as survey
      interviewers. While the evaluation methodology adopts a quasi-experimental
      approach, the appointment of local residents as survey interviewers reflects an
      alternative (interpretive) research tradition. The combined strategy constitutes
      a postpositivist methodology in that it combines a data collection strategy more
      akin to interpretive social science while retaining a positivistic
      epistemological framework. The paper describes some logistics of this approach
      and problems encountered during the course of survey. While many of the problems
      described may be routinely associated (although seldom aired) with survey work,
      particularly in disadvantaged areas, the paper suggests they are also a function
      of the postpositivist research strategy which we adopted. The failure to involve
      interviewers in the conception and development of the evaluation meant that they
      lacked identification with our endeavour and this had practical implications for
      the survey interviewing. Although the survey was successfully executed and the
      employment of local residents was a valuable and worthwhile experience, the
      authors recognize that this narrow conception of user involvement meant that many
      of the potential benefits (both to the research and the participants) associated
      with participatory approaches were forfeited.

PMID- 11345664
TI  - Empowering counseling--a case study: nurse-patient encounter in a hospital.
AB  - This study illustrates practices that a nurse uses in order to empower patients.
      The emphasis is on speech formulae that encourage patients to discuss their
      concerns and to solicit information about impending surgery. The study is a part
      of a larger research project and a single case was selected for presentation in
      this article because it differed from the rest of the data by manifesting
      empowering practice. A videotaped nurse-patient health counseling session was
      conducted in a hospital and transcribed verbatim. The investigator interviewed
      the nurse and the patient after the conversation, and these interviews were
      transcribed as well. The encounter that is presented here as a case study is a
      concrete example of a counseling session during which the patient is free to
      discuss with the nurse. The empowering practices that the nurse employed were as
      follows: encouraging the patient to speak out, tactfully sounding out the
      patient's concerns and knowledge of impending surgery, listening to feedback, and
      building a positive vision of the future for the patient. We suggest that nurses
      should pay attention to verbal expression and forms of language. This enables
      them to gain self-awareness and discover new tools to work with.

PMID- 11345665
TI  - What's wrong with this benchmark report?

PMID- 11345666
TI  - Billing basics: a review course.
AB  - Each year, practice management should thoroughly examine the billing and
      collections operation and set goals. This review course, while not all-inclusive,
      should serve as a guide, reminder and perhaps catalyst to that process.

PMID- 11345667
TI  - Internet supply ordering. Helping medical group practices improve business
      operations.
AB  - Technology has opened the door to a new world of management tools in the
      physician practice environment. Productivity aids on the Web promise to alter
      forever the way we do everything--from interacting with vendors to caring for
      patients. Online medical, surgical and pharmaceutical supply acquisition sites,
      for example, already offer more efficient alternatives to phone and fax ordering,
      back-order challenges and supply cost monitoring. Not all sites are the same,
      however, and physicians and practice administrators must compare and contrast
      their needs with site offerings.

PMID- 11345668
TI  - Are hospitals prematurely divesting their employed physician groups?
AB  - This article reviews the original strategic decisions for hospitals developing
      employed physician groups and assesses whether the strategic reasons are still
      valid. It then discusses the factors that have the greatest impact on the
      profitability of these groups. A number of hospitals have found that the original
      strategic reasons for employing physicians still apply, and they have taken a
      multifaceted approach, developing expense, reimbursement and other key strategies
      to improve profitability and preserve their initial objectives.

PMID- 11345670
TI  - Compliance plans within the organizational context of physician practices. What
      may need to change?
AB  - The Office of the Inspector General's (OIG's) compliance guidelines for
      individual and small group practices will require a range of operational changes.
      This is part 2 of a two-part article describing the guidelines' impact on small-
      and in some cases large--practices, and the ways to meet their requirements. Part
      1 appeared in the September/October 2000 issue of MGM Journal. The author
      presented questions that practices can use to assess the extent of operational
      and organizational changes necessary to integrate a compliance program. This
      second part addresses operational changes that may be necessary.

PMID- 11345669
TI  - A software application that answers the need for an enterprise budgeting tool.
AB  - A prototype software application developed for the Vanderbilt University School
      of Medicine answered our need for an enterprise budgeting tool--one that has
      application across the entire organization. This application, built on Microsoft
      Access, provides a flexible user interface without requiring sophisticated
      technical support.

PMID- 11345671
TI  - Health insurance for the "uninsurable".
AB  - State-sponsored health insurance plans for people labeled "uninsurable" by
      commercial carriers provide financial lifelines for those who qualify. In 28
      states, individuals suffering from cancer, AIDS, multiple sclerosis, emotional
      disorders, cystic fibrosis, para- or quadriplegia and other chronic or recurrent
      health problems receive benefits--for reasonable premiums--from innovative
      programs that can literally make the difference between life and death, solvency
      or indigence. Medical practices and other health care facilities can play a
      pivotal role in informing patients of these coverage options--and by doing so,
      increase their revenue, as well.

PMID- 11345672
TI  - "We didn't get the claim," and other payer excuses.
AB  - How many times have you heard from a third-party payer, "we don't have the
      claim"? Is it only the health insurance industry that has problems receiving its
      mail and electronic transmissions? Rather than spend time beating up on the
      payers, the author provides constructive and proactive approaches to help
      identify why claims fall into a black hole and how to avoid pitfalls.

PMID- 11345673
TI  - The genesis of syringe prescription to prevent HIV in Rhode Island.

PMID- 11345674
TI  - Criminal prosecution for HMO treatment denial.

PMID- 11345675
TI  - Medicaid and Viagra: restoring potency to an old program?

PMID- 11345676
TI  - Harm reduction in the health care system: the legality of prescribing and
      dispensing syringes to drug users.

PMID- 11345677
TI  - Federal law and syringe prescription and dispensing.

PMID- 11345678
TI  - Liability for prescribing intravenous injection equipment to i.v. drug users.

PMID- 11345679
TI  - An analysis of ethical issues in prescribing and dispensing syringes to injection
      drug users.

PMID- 11345680
TI  - [Bio-metabolic changes produced by 2 commercial fluoride-containing compounds on
      human keratinocytes].
AB  - BACKGROUND: Although fluoride has been used for decades either systemically or
      topically to prevent dental caries, the cellular and molecular mechanisms
      underlying its action are poorly understood. METHODS: An in vitro study of the
      human keratinocyte cell line NCTC 2544 was conducted in the presence of two
      different fluoride-containing commercial compounds (Zymafluor and Elmex) to
      investigate their toxicity threshold and the sequence of events involved in
      fluoride ion toxicity in this cell population. The toxicity threshold was
      determined by incubating cells with rising concentrations of Zymafluor and Elmex
      for 20 h. The study of the sequence of events involved in ion toxicity was
      performed through a time-effect study by exposing cells to 4 mM fluoride ions and
      testing them at 2, 6, and 20 h. Cell viability and ultrastructural parameters
      were assessed: degree of confluence, semiquantitative assessment of dead cells
      and debris in the supernatant, and morphology. RESULTS: Ultrastructural
      morphological analysis showed different cell behaviours with the two compounds;
      moreover, their toxic effect appeared to be both concentration- and time
      dependent. CONCLUSIONS: These data underline the susceptibility of the
      intracellular communication system to fluoride and show that exceeding the
      therapeutic dose of fluoride involves substantial risk of toxicity.

PMID- 11345681
TI  - [Involvement of the submadibular region in epidermoid carcinoma of the mouth
      floor. Prospective study of 31 cases].
AB  - BACKGROUND: To evaluate the primary or secondary involvement of the submandibular
      gland in floor of mouth squamous cell carcinoma. METHODS: An analytic
      observational study of prospective type was carried out on 31 patients operated
      for floor of mouth carcinoma, between June 1993 and January 1996, in a reference
      hospital for a population of 1,100,000 inhabitants. The investigated variables
      were: age, sex, tumor localization, clinical TNM, type of cervical surgery,
      evolution, number of positive cervical metastasis, state of the submandibular
      gland and presence of the periglandular metastasis. The follow-up period was
      about 48 to 76 months. The exact Fischer test was used for the statistical study.
      RESULTS: Histopathological examination identified cervical metastasis as 34.1% of
      the ipsilateral neck dissections. The average number of positive nodes was 3
      (range: 1-9). Cervical periglandular metastases were found in 31.7% of neck
      dissections, but in no case was microscopic affectation of the submandibular
      gland found. The existence of intraglandular positive nodes was not found either.
      In our study, the sensibility and specificity of the clinical exploration of the
      submandibular region were high (84% and 88% respectively). The presence of
      cervical metastasis and the size of the tumor conditioned the appearance of
      recurrences. CONCLUSIONS: In accordance with our study, periglandular metastases
      in carcinoma of the floor of mouth, are frequent, but submandibular gland
      involvement is unusual.

PMID- 11345682
TI  - [Posterior vertical dimension and condylo-discal non-coordination of the
      temporomandibular joint. Hypothesis on correlation].
AB  - BACKGROUND: On the basis of clinical evidence, an analytic study has been carried
      out to verify the hypothetic correlation between reduction of the posterior
      vertical overlap and internal derangements. METHODS: 58 patients with
      temporomandibular disorders have been observed; they presented clinically a
      reduction of the posterior vertical dimension (RPVD) due either to the loss of
      molar teeth or to the molar occlusal surface abrasion or to a wrong prosthetic
      rehabilitation. A cephalometric exam showed a significative correspondence
      between the RPVD and the retruded condylar position in the glenoidae fossa with a
      reduction of posterior joint space in comparison with the standard values
      purposed by Farrar. RESULTS: The results obtained showed a possible relation
      between occlusal alterations and the TMJ pathology. CONCLUSIONS: The conclusion
      is drawn that the clinical evaluation brings to consider occlusal factors, and in
      particular the reduction of posterior vertical dimension may be considered as
      possible etiologic factors of TMJ disorders.

PMID- 11345683
TI  - [Stomatologic approach in patients with congenital coagulation deficit].
AB  - BACKGROUND: The purpose of the present paper was to resolve postoperative
      bleeding after oral surgery in patients with congenital coagulative defects,
      avoid transfusion of clotting factors and improve the patient's quality of life.
      METHODS: Since 1988, 1598 oral surgery procedures have been performed on patients
      with congenital coagulative defects treated with a protocol including pre- and
      postoperative tranexamic acid rinses. RESULTS: The use of tranexamic acid mouth
      washing has obtained effective hemostasis in 86% of cases and only 4% of surgical
      procedures required clotting factor transfusions. CONCLUSIONS: The results
      suggest that mouth washing with tranexamic acid prevents excessive oral bleeding
      in patients with congenital deficit of the coagulation system. Furthermore, a
      total elimination of the granulation tissue, that reduces the possibility of
      activation of the fibrinolytic mechanism, is also important.

PMID- 11345685
TI  - Associated localization of morphea and lichen planus of the lip in a patient with
      vitiligo.
AB  - Morphea, lichen planus and vitiligo are common diseases, but seldom associated.
      Morphea or lichen planus in the lips have not frequently been reported, and an
      associated localization of both lesions in the lip mucosa is indeed a rare event.
      A case of morphea and lichen planus localized in the upper lip mucosa in a
      patient with vitiligo is reported. Immunohistochemistry revealed a clear
      prevalence of T-lymphocytes in the inflammatory infiltrates of morphea and in the
      band-like infiltrate of the lichen, a finding consistent with previous reports of
      morphea, lichen planus, and vitiligo. The inverse ratio found between CD8+ and
      CD4+ lymphocytes, compared to other reports, seems to confirm that the
      pathogenesis of morphea and lichen planus evolves through different stages. The
      present report, besides presenting a rare case, may prompt to consider a common
      pathogenesis among morphea, lichen planus and vitiligo.

PMID- 11345684
TI  - [Muscular physiotherapy in patients with temporomandibular disorders. Controlled
      clinical trial].
AB  - BACKGROUND: The purpose of the present study is to evaluate the short term
      effects of physiotherapy and counseling in the treatment of myofascial pain of
      the jaw muscles. METHODS: Forty consecutive myogenous TMD patients, were assigned
      to two treatment groups with a balanced-block randomization. The first group
      received only counseling, the second group received counseling supplemented by
      physiotherapy. The patients were followed for a period of three months. Data were
      collected on two different occasions: T0 = baseline and T1 = three months after
      the start of treatment. Treatment success was decided on the basis of an index
      called treatment contrast (Tc). It allowed a subjective, an objective and a total
      evaluation of the effects of the two therapeutic protocols. RESULTS: There was no
      significant difference between groups in the outcome measures except for the
      subjective evaluation of treatment success: physiotherapy seems to be slightly
      more effective than counseling. CONCLUSIONS: Elective therapy for the treatment
      of TMD patients remains the conservative one. Success of this therapy depend on a
      good patient--clinician relation, which improves patient's compliance.

PMID- 11345686
TI  - [Efficacy of 4 adhesive systems for amalgam. In vitro study].
AB  - BACKGROUND: The aim of this research is to study the shear bond strength of 4
      adhesive systems of the last generation: All-Bond 2 (AB2), Clearfil Liner Bond 2
      (CL), Scotchbond MP plus (SBMP) and High Q Bond plus (HQB). According to the
      manufacturing company these products are suitable for amalgam adhesion to dentin.
      METHODS: Forty extracted human third molars have been ground to expose a flat
      dentin surface. The teeth were randomly assigned to 4 groups, and every group was
      treated with one of the adhesive system according to the manufacturer's
      instructions. Samples were then secured in a split Teflon mould, having a 6 mm
      diameter opening and a spherical amalgam was triturated and condensed onto the
      treated dentin surfaces. The amalgam cylinders have been exposed to a tensile
      bond test using a Universal Testing Machine (Instron 4500). ANOVA test has been
      used to the statistic study among groups. RESULTS: The study of the tensile mean
      range, showed that dentin shear bond strength values (MPa) for the adhesive
      systems tested were: 8.13 +/- 1.48 for AB2, 7.06 +/- 1.41 for SBMP, 4.2 +/- 1.06
      for HQB, 3.04 +/- 0.68 for CL. The statistic test revealed significant
      differences among the 4 groups (p < 0.05). CONCLUSIONS: The bond strength mean
      values of amalgam adhesives are lower than the ones for composite resins,
      nevertheless dentin-enamel adhesive systems specific for amalgam have to be taken
      into consideration particularly in case of conservative restorations that need
      chemical retention as a support, when the mechanical one is not enough.

PMID- 11345687
TI  - [Efficacy of and tolerance to topical ketoprofen lysinate solution in acute
      inflammation of the mouth in orthodontic therapy. Randomized single blind study,
      with parallel groups, versus benzidamine hydrochloride].
AB  - BACKGROUND: The study was carried out to value the analgesic efficacy of
      ketoprofen lysinate solution administered by oral route. Ketoprofen lysinate
      solution is an efficacious topical drug for pain relief and control of
      inflammation agents. METHODS: The study was carried out in 120 patients submitted
      to orthodotic therapy by oral route, under single blind conditions at the "San
      Raffaele" Hospital in Milan. The 120 patients who underwent orthodonthic therapy
      were males and females, from 18 to 40 years old. One group was treated with
      ketoprofen lysinate solution at the doses of 160 mg in 100 ml (60 patients), the
      other group with benzidamine hydrochloride 15 ml (60 patients), twice a day for
      seven days. Pain relief and control of inflammation agents have been evaluated.
      RESULTS: The study showed ketoprofen lysinate solution to be very effective for
      pain relief and control of inflammation agents. In fact, on the basis of the
      visual analogue scale of Scott-Huskisson and of the patient's judgement,
      ketoprofen proved significantly better than benzidamine. CONCLUSIONS: The
      analgesic efficacy of ketoprofen lysinate solution administered by oral route was
      prompt and long lasting than benzidamine. Both treatments were very well
      tolerated.

PMID- 11345688
TI  - Polysaccharides from lichens: structural characteristics and biological activity.
AB  - Lichens have been used for medicinal purposes throughout the ages, and beneficial
      claims have to some extent been correlated with their polysaccharide content. Of
      13,500 lichen species growing worldwide, less than 100 species have been
      investigated for polysaccharide content. Lichen polysaccharides are mainly of
      three different structural types: beta-glucans, alpha-glucans, and
      galactomannans. In addition, a few complex heteroglycans have recently been
      described, such as thamnolan, a water-soluble, immunologically active
      heteroglycan with a novel rhamnopyranosylgalactofuranan type of structure. A
      number of investigations have been carried out on biological effects of lichen
      polysaccharides, most notably antitumour, immunomodulating, antiviral, and memory
      enhancing effects. The current review summarizes present knowledge on the
      structural characteristics and biological activity of lichen polysaccrides.

PMID- 11345689
TI  - Effect of salicis cortex extract on human platelet aggregation.
AB  - The bark of Salix species contains several prodrugs of salicylate, mainly
      salicin. The aim of this study was to investigate if during pain treatment with
      Salicis cortex extract platelet aggregation was affected. A total of 51 patients
      were enrolled in the study. Thirty-five patients suffering from acute
      exacerbations of chronic low back pain received randomly and double-blind either
      Salicis cortex extract with 240 mg salicin/day (n = 19) or placebo (n = 16).
      Further sixteen patients with stable chronic ischemic heart disease were given
      100 mg acetylsalicylate per day. Platelet aggregation was studied using an
      aggregometer. As aggregating agents, arachidonic acid (500 micrograms/ml),
      adenosine di-phosphate (2 x 10(-5) M) and collagen (0.18 microgram/ml) were used.
      The mean maximal arachidonic acid induced platelet aggregation was 61%, 78% and
      13% in the Salicis cortex extract, placebo and acetylsalicylate groups.
      Acetylsalicylate had a significant inhibitory effect on platelet aggregation
      compared to Salicis cortex extract (p = 0.001) and placebo (p = 0.001). There was
      also a significant difference between the placebo and the willow bark-treated
      groups in the maximal platelet aggregation induced by arachidonic acid (p = 0.04)
      and ADP (p = 0.01). No statistical difference was found between the groups when
      collagen was applied to the human platelets. Daily consumption of Salicis cortex
      extract with 240 mg salicin per day affects platelet aggregation to a far lesser
      extent than acetylsalicylate. Further investigation needs to clarify if this
      finding is of clinical relevance in patients with impaired thrombocyte function.

PMID- 11345690
TI  - In vitro inhibitory effect of protopanaxadiol ginsenosides on tumor necrosis
      factor (TNF)-alpha production and its modulation by known TNF-alpha antagonists.
AB  - Ginsenosides are the major principles of Panax ginseng C. A. Meyer (Araliaceae)
      used as a mild oriental folk medicine. In this report, we have examined the
      inhibitory potency of protopanaxadiol ginsenosides (PPDGs) such as Rb1, Rb2 and
      Rc, and their co-treatment effect with known tumor necrosis factor (TNF)-alpha
      antagonists on TNF-alpha production in either murine (RAW264.7) or human (U937)
      macrophages stimulated with lipopolysaccharide (LPS). Rb1, and Rb2 strongly
      suppressed TNF-alpha production in RAW264.7 cells with an IC50 of 56.5 and 27.5
      microM, respectively, and in differentiated U937 cells with an IC50 of 51.3, and
      26.8 microM, respectively. The inhibitory activity of Rb1 and Rb2 was
      significantly increased by pharmacological agents against protein kinase C,
      protein tyrosine kinase, and protein kinase A, and anti-rheumatoid arthritis
      drugs, such as chloroquine and steroid drugs. In contrast, only cyclic AMP
      phosphodiesterase (cAMP PDE) inhibitors among cAMP-elevating agents did not
      change the inhibitory potency of PPDGs. These data suggest that PPDGs may possess
      potential therapeutic efficacy against TNF-alpha mediated disease and the
      therapeutic potency of PPDGs may be enhanced when co-treated with various kinds
      of known TNF-alpha antagonists but not with cAMP PDE inhibitors.

PMID- 11345691
TI  - Lignan and phenylpropanoid glycosides from Phillyrea latifolia and their in vitro
      anti-inflammatory activity.
AB  - Three phenylpropanoid glycosides (salidroside, syringin and coniferin) and one
      lignan (phillyrin) isolated from the leaves of Phillyrea latifolia L. (Oleaceae)
      were tested for interactions with the cyclo-oxygenase and 5-lipoxygenase pathways
      of arachidonate metabolism in calcium-stimulated mouse peritoneal macrophages and
      human platelets, and for their effects on cell viability. These compounds are
      capable of exerting inhibitory actions on enzymes of the arachidonate cascade.
      Phillyrin, salidroside and syringin exert a preferential effect on the cyclo
      oxygenase pathway, inhibiting release of the cyclo-oxygenase metabolites
      prostaglandin E2 (IC50 values 45.6 microM, 72.1 microM and 35.5 microM,
      respectively) and to a lesser extent reducing thromboxane B2 levels (IC50 values
      168 microM, 154 microM and 29.3 microM, respectively). In contrast, coniferin can
      be classified as a "dual inhibitor", since it produces reduction in generation of
      both cyclo-oxygenase (IC50 values 75.2 microM for prostaglandin E2 and 619 microM
      for thromboxane B2) and 5-lipoxygenase metabolites, but the effects are greater
      against leukotriene C4 (IC50 value 63.6 microM). Structure-activity relationships
      of the three phenylpropanoid glycosides are discussed. Thus, like some other
      compounds found in medicinal herbs, our molecules possess an array of potentially
      beneficial anti-eicosanoid properties which may, alongside other constituents,
      contribute to the claimed therapeutic properties of the plant from which they are
      derived.

PMID- 11345692
TI  - Mechanisms of relaxant action of S-petasin and S-isopetasin, sesquiterpenes of
      Petasites formosanus, in isolated guinea pig trachea.
AB  - We investigated the mechanisms of action of S-petasin and S-isopetasin, from
      Petasites formosanus Kitamura which is used as a folk medicine for treating
      hypertension, tumors, and asthma in Taiwan. The tension changes of tracheal
      segments were isometrically recorded on a polygraph. S-Petasin and S-isopetasin
      non-competitively inhibited cumulative histamine-, and carbachol-induced
      contractions with an exception that S-isopetasin produced a parallel, rightward
      shift of the concentration-response curve of carbachol in a competitive manner. S
      Petasin also non-competitively inhibited cumulative Ca(2+)-induced contractions
      in depolarized (K+, 60 mM; histamine, 100 microM; or carbachol, 10 microM) guinea
      pig tracheas. S-Isopetasin did in depolarized (K+, 60 mM) trachea too. The
      nifedipine (10 microM)-remaining tension of carbachol (0.2 microM)-induced
      precontraction was further relaxed by S-petasin or S-isopetasin, suggesting that
      no matter whether either blocked VDCCs or not, S-petasin or S-isopetasin may have
      other mechanisms of relaxant action. The relaxant effect of S-petasin or S
      isopetasin was unaffected 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, S-petasin (100-300 microM), but not S-isopetasin, significantly
      inhibited cAMP-, but not cGMP-dependent PDE activity of the trachealis. The above
      results reveal that the mechanisms of relaxant action of S-petasin and S
      isopetasin may be primarily due to its non-specific antispasmodic and
      antimuscarinic effects, respectively.

PMID- 11345693
TI  - Artery relaxation by chalcones isolated from the roots of Angelica keiskei.
AB  - An EtOAc-soluble fraction from a 50% EtOH extract of the roots of Angelica
      keiskei inhibited phenylephrine-induced vasoconstriction in rat aortic rings,
      while an EtOAc-insoluble fraction had no effect at 100 micrograms/ml. Five active
      substances isolated from the EtOAc-soluble fraction of the roots were identified
      as xanthoangelol (1), 4-hydroxyderricin (2), and xanthoangelols B (3), E (4) and
      F (5), which inhibited phenylephrine-induced vasoconstriction at the
      concentrations of 10-100 micrograms/ml. It was found that xanthoangelol (1), 4
      hydroxyderricin (2), and xanthoangelols E (4) and F (5) inhibited the
      phenylephrine-induced vasoconstriction through endothelium-dependent endothelium
      derived relaxing factor (EDRF) production and/or nitric oxide (NO) production.
      Among the five chalcones, xanthoangelol B (3) inhibited the phenylephrine-induced
      vasoconstriction most strongly, and it inhibited the phenylephrine-induced
      vasoconstriction in the presence or absence of endothelium and in the presence or
      absence of NG-monomethyl-L-arginine (L-NMMA) (an NO synthetase inhibitor).
      Furthermore, 4-hydroxyderricin (2) and xanthoangelol B (3) at concentrations of
      10-100 micrograms/ml concentration-dependently inhibited the elevation of
      intracellular free calcium [Ca2+]i induced by phenylephrine. These results
      demonstrate that compounds 1, 2, 4 and 5 inhibit phenylephrine-induced
      vasoconstriction through endothelium-dependent production of EDRF/NO and/or
      through the reduction of the [Ca2+]i elevation induced by phenylephrine. On the
      other hand, the inhibitory mechanism of compound 3 on phenylephrine-induced
      vasoconstriction might involve the direct inhibition of smooth muscle functions
      through the reduction of [Ca2+]i elevation without affecting EDRF/NO production.

PMID- 11345694
TI  - The coumarin osthol attenuates the binding of thyrotropin-releasing hormone in
      rat pituitary GH4C1 cells.
AB  - The influence of two plant coumarins, osthol and xanthotoxin, on intracellular
      Ca2+ ([Ca2+]i) transients evoked by TRH were studied in clonal rat pituitary
      GH4C1 cells. Osthol, but not xanthotoxin, decreased the TRH-induced transient
      increase in [Ca2+]i in Fluo-3 loaded cells incubated in Ca(2+)-free buffer.
      Binding experiments with [3H]TRH showed that osthol decreased the binding of TRH
      to its receptor, whereas the affinity of the receptor for TRH increased. This
      resulted in a decreased TRH-evoked production of IP3 in cells treated with
      osthol, and a decreased mobilization of sequestered calcium. Osthol did not
      inhibit the release of calcium evoked by exogenous IP3 in permeabilized cells.
      Furthermore, osthol decreased the uptake of 45Ca2+ in response to high K+.
      Xanthotoxin had no effects in these experiments. The results show that osthol
      modulates TRH-evoked responses by interacting with the TRH receptor.

PMID- 11345695
TI  - Inhibitory effect of (+)-catechin on the growth of influenza A/PR/8 virus in MDCK
      cells.
AB  - We investigated whether (+)-catechin, a building block of tannins contained in
      the extract of Ephedrae herba (EHext), exerts an inhibitory effect on the
      acidification of intracellular compartments such as endosomes and lysosomes
      (referred to as ELS), and thereby inhibits the growth of influenza A PR/8/34
      (PR8) virus (H1N1 subtype) in Madin-Darby canine kidney cells. The vital
      fluorescence microscopic study with acridine orange showed that 1-h treatment
      with (+)-catechin inhibited the acidification of ELS in a concentration-dependent
      manner (1.0-10.0 mM). Moreover, the growth of PR8 virus was inhibited markedly
      when the cells were treated with (+)-catechin (1.25-10.0 mM) for 1 h immediately
      after infection, or treated within as little as 5 to 10 min after infection.
      Conversely, virus growth resumed within 3 h concomitantly with the reappearance
      of acidified ELS after removal of (+)-catechin. Similar to EHext, (+)-catechin
      inhibited both the acidification of ELS and the influenza virus growth. It
      suggests that (+)-catechin is one of the active components in EHext.

PMID- 11345697
TI  - Decreased scopolamine yield in field-grown Duboisia plants regenerated from hairy
      roots.
AB  - Hairy root cultures were obtained from hybrid clones of Duboisia myoporoides x D.
      leichhardtii following transformation by Agrobacterium rhizogenes strain A4.
      Shoots spontaneously regenerating from the hairy root cultures were rooted and
      transferred to soil. The plants displayed typical morphological alterations known
      as hairy root syndrome to varying degrees. PCR analysis confirmed that all
      transformed plants contained the rolA, rolB and rolC genes, irrespective of the
      degree of morphological alterations. A field test of the transformed regenerated
      plants revealed that those plants displaying the strongest hairy root syndrome
      symptoms had the highest content of the tropane alkaloid scopolamine. However,
      the overall scopolamine and hyoscyamine yield of all transformed plants was
      clearly reduced compared to untransformed control plants. These results
      demonstrate that the A. rhizogenes-transformed plants tested in this study do not
      provide a viable alternative to agricultural farming of hybrid clones of D.
      myoporoides x D. leichhardtii obtained by conventional breeding.

PMID- 11345696
TI  - The positive inotropic and chronotropic effects of evodiamine and rutaecarpine,
      indoloquinazoline alkaloids isolated from the fruits of Evodia rutaecarpa, on the
      guinea-pig isolated right atria: possible involvement of vanilloid receptors.
AB  - Cardiotonic effects of evodiamine and rutaecarpine, constituents of the fruits of
      Evodia rutaecarpa Bentham Rutaceae, were evaluated on guinea pig isolated atria.
      Comparison with capsaicin, a vanilloid receptor agonist, revealed similar
      positive inotropic and chronotropic activity, as judged from antagonistic effects
      of the competitive vanilloid receptor (capsaicin receptor) antagonist
      capsazepine, the non-competitive vanilloid receptor antagonist ruthenium red, the
      calcitonin gene related peptide antagonist CGRP(8-37), the P2X purinoceptor
      antagonist PPADS, and various desensitization studies. Evodiamine and
      rutaecarpine produced transient positive inotropic and chronotropic effects on
      the guinea-pig isolated atria, followed by a desensitizing effect to additional
      administration. Dose-response relationships for evodiamine, rutaecarpine and
      capsaicin were obtained. All the compounds evoked positive inotropic and
      chronotropic effects in a concentration-dependent manner. Maximal contractions
      for evodiamine, rutaecarpine and capsaicin were observed at concentrations of 1
      microM, 3 microM and 0.3 microM, respectively. The cardiotonic responses evoked
      by both evodiamine and rutaecarpine were shifted to the right by capsazepine, an
      established antagonist of vanilloid receptor (capsaicin-receptor). The effects of
      both evodiamine (1 microM) and rutaecarpine (3 microM) were abolished by
      pretreatment with a desensitizing dosage of capsaicin (1 microM), developing
      cross-tachyphylaxis between these compounds. The effects of evodiamine (1
      microM), rutaecarpine (3 microM) and capsaicin (0.3 microM) were also
      significantly reduced by pretreatment with ruthenium red (10 microM) and CGRP (8
      37) (10 microM). The effects of evodiamine, rutaecarpine and capsaicin were not
      affected by pretreatment with PPADS (100 microM), a highly selective P2X
      purinoceptor antagonist, and the possibility of the involvement of the P2X
      purinoceptor was excluded. These results suggest that the positive inotropic and
      chronotropic effects on the guinea-pig isolated right atria induced by both
      evodiamine and rutaecarpine could be attributed to their interaction with
      vanilloid receptors and the resultant release of CGRP, a cardiotonic
      neurotransmitter, from capsaicin-sensitive nerves as with capsaicin.

PMID- 11345698
TI  - Effect of light on hypericins contents in fresh flowering top parts and in an
      extract of St. John's Wort (Hypericum perforatum).
AB  - St. John's Wort is a medicinal plant increasingly used for its antidepressive
      activity. Hypericins are considered as one of the compounds contributing to the
      activity of the extract. These naphthodianthrones exist in various forms in
      Hyperici herba. Protopseudohypericin and protohypericin (protopigments) are
      converted into pseudohypericin and hypericin (pigments) under the action of
      light. The aim of this work is to study the influence of light on the
      phototransformation of protopigments into pigments. Two experiments were carried
      out. The studies were performed on one hand, on plant material in order to know
      the proportion of these substances in various plant parts and the possibility of
      transforming the protopigments into pigments under the action of sunlight; on the
      other hand, in the extract to determine the optimal wavelength allowing this
      transformation. Three parts of the fresh plant (buds, flowers, leaves) were
      treated with sunlight on three levels of exposure. Liquid extracts were exposed
      to various types of light with wavelengths ranging between 480 and 660 nm by
      means of diodes. The flowering tops of St. John's Wort contain a share of
      approximately 30% hypericins in the form of protopseudohypericin and
      protohypericin: buds (48%), flowers (30%), leaves (17%). After an exposure of
      fresh buds to sunlight for 16 hours the share of protopigments was then 32%. In
      the extract, the transformation of the protopigments is total and requires less
      energy than in the plant material. The optimal wavelength for the transformation
      of the protopigments in the extract is around 515 nm (green), close to the
      optimum absorption level of protopigments.

PMID- 11345700
TI  - Microbiological status of commercially available medicinal herbal drugs--a
      screening study.
AB  - One hundred and thirty-eight medicinal herbal drugs obtained from different
      suppliers were examined for microbial contaminants and for the detectability of
      pathogenic microorganisms. For this purpose, several microbiological standard
      parameters (total aerobic mesophilic count, enterobacteria, coliforms, aerobic
      sporeformers, yeasts and moulds, enterococci, lactobacilli, pseudomonades and
      aeromades) and selective methods for the detection of indicator microorganisms
      and pathogens (E. coli, enterohaemorrhagic E. coli [EHEC], Salmonella,
      Campylobacter jejuni, Pseudomonas aeruginosa, Bacillus cereus, Clostridium
      perfringens, Listeria, coagulase-positive staphylococci, Candida albicans,
      potentially aflatoxigenic moulds) were applied. The microbial load of the samples
      varied considerably. While none of the samples contained EHEC, Salmonellae,
      Pseudomonas aeruginosa, Listeriae, Staphylococcus aureus or Candida albicans,
      four samples were E. coli positive, two samples were presumptively Campylobacter
      jejuni positive and nine herbal drugs contained a potentially aflatoxigenic mould
      flora. Further details regarding different viable count classes as well as
      preparation techniques are discussed.

PMID- 11345699
TI  - Different stereoselectivity in the reduction of pulegone by Mentha species.
AB  - Aqueous solutions of [2H]-labeled pulegone enantiomers were fed to Mentha spicata
      ssp. spicata L. and Mentha spicata ssp. crispata L. shoot tip and first leaf
      pair. After solid phase microextraction the essential oil was analysed with
      enantioselective multidimensional gas chromatography/mass spectrometry. Both
      Mentha spicata species were able to convert labelled (1R)- and (1S)-pulegone at
      the same rate into the corresponding menthone and isomenthone, indicating an
      unspecific process. The reduction of both pulegone enantiomers preferably led to
      the cis-stereoisomers. The observed stereoselectivity is completely different
      from those of pulegone reduction by Mentha x piperita L.

PMID- 11345701
TI  - Pregnane glycoside, lignan glycosides, triterpene glycosyl ester and flavonoid
      glycosides from Rubus amabilis.
AB  - Two new compounds, 3-O-beta-D-glucopyranosyl-3 beta, 15 alpha-dihydroxypregn-5-en
      20-one (1) and (-)-secoisolariciresinol-O-alpha-L-rhamnopyranoside (2), along
      with six known compounds (3-8), have been isolated from the aerial parts of Rubus
      amabilis Focke. The structures of the new compounds were elucidated mainly by
      spectroscopic methods and some chemical transformations.

PMID- 11345702
TI  - Effect of genistein analogs on oxygen radical production in leukocytes stimulated
      by unopsonized zymosan.
AB  - Effects of genistein analogs on oxygen radical production have been analyzed in
      human neutrophils, human monocytes or murine macrophages Raw264.7 stimulated with
      unopsonized zymosan by lucigenin- and luminol-enhanced chemiluminescence assays.
      Genistein exhibited IC50 values of 10.7-11.5 microM on the oxygen radical
      production in human neutrophils, 10.9-11.0 microM in human monocytes, and 14.8
      27.3 microM in Raw264.7 cells. Orobol, a genistein analog with an additional
      hydroxy group at the 3' position, exhibited IC50 values of 3.0-3.3 microM on the
      oxygen radical production in human neutrophils, 2.8-3.1 microM in human
      monocytes, and 1.5-3.9 microM in Raw264.7 cells. Genistin and sophoricoside are
      genistein glycosides with a glucose moiety at 7 or 4' position, respectively. The
      genistein glycosides exhibited 23-37% inhibitory effects at 100 microM on the
      oxygen radical production.

PMID- 11345703
TI  - Isolation of virus-cell fusion inhibitory components from Eugenia caryophyllata.
AB  - The fractionation of Eugenia caryophyllata (Myrtaceae) guided by the syncytia
      formation inhibition assay led to the isolation of four tannins (eugeniin,
      casuarictin, 1,3-di-O-galloyl-4,6-(S)-hexahydroxydiphenoyl-beta-D-glucopyranose,
      and tellimagrandin I), and two chromones (biflorin and isobiflorin). Among the
      isolated compounds, tellimagrandin (4) showed a significantly high inhibitory
      activity on the syncytia formation with an IC50 value of 16.12 +/- 1.98
      micrograms/ml.

PMID- 11345704
TI  - A new antimycobacterial, 3 beta-acetoxy-15 alpha,22-dihydroxyhopane, from the
      insect pathogenic fungus Aschersonia tubulata.
AB  - Bioassay-guided fractionation of the cell extract of the insect pathogenic fungus
      Aschersonia tubulata BCC 1785 led to the isolation of dustanin (1), 3 beta,15
      alpha,22-trihydroxyhopane (3), 5 alpha,8 alpha-epidioxy-24(R)-methylcholesta-6,22
      diene-3 beta-ol (6), together with the new 3 beta-acetoxy-15 alpha,22
      dihydroxyhopane (4). Chemical structures of these compounds were elucidated by
      spectral analyses as well as chemical transformation. Compounds 1 and 4 exhibited
      antimycobacterial activity with the minimum inhibitory concentration (MIC) of
      12.5 micrograms/ml.

PMID- 11345705
TI  - Vasorelaxing effect of coumarins from Cnidium monnieri on rabbit corpus
      cavernosum.
AB  - Bioassay-directed fractionation led to the identification of four known
      coumarins, osthole (1), imperatorin (2), xanthotoxin (3), and isopimpinellin (4),
      from the ethanolic extract of the fruit of Cnidium monnieri (L.) Cusson. In
      phenylephrine (PE)-precontracted endothelium-intact rabbit corpus cavernosum, all
      four coumarins exhibited relaxing effect with the IC50 values for compounds 1, 2,
      3, and 4 determined to be 2.14 +/- 0.73, 0.85 +/- 0.16, 1.24 +/- 0.45, and 18.4
      +/- 8.10 microM, respectively. The four compounds were identified by comparison
      of their physical data (EIMS, 1H- and 13C-NMR) with those from published reports.

PMID- 11345706
TI  - Antidiarrhoeal activity of piperine in mice.
AB  - Peppers are common food ingredients used worldwide. They are also added in
      traditional antidiarrhoeal formulations of different herbs. Piperine (1) is an
      alkaloidal constituent of black and long peppers recently established as a
      bioavailability enhancer of drugs and other substances. As a part of efforts to
      study its effects on the gastrointestinal tract, the experiments were performed
      to determine the rationale, if any, for its use in traditional antidiarrhoeal
      formulations. Antidiarrhoeal activity of 1 against castor oil, MgSO4 and
      arachidonic acid was studied in mice. It significantly inhibited diarrhoea
      produced by these cathartics at 8 and 32 mg/kg p.o. dose. Inhibition of castor
      oil induced enteropooling by 1 suggests its inhibitory effect on prostaglandins.
      The results validate the rationale for its use in traditional antidiarrhoeal
      formulations.

PMID- 11345707
TI  - New flavonol glycosides from the flowers of Aconitum napellus ssp. tauricum.
AB  - From the methanolic extract of the flowers of A. napellus spp. tauricum four new
      flavonol glycosides: quercetin 3-O-(6-trans-caffeoyl)-beta-glucopyranosyl-(1-->2)
      beta-glucopyranoside-7- O-alpha-rhamnopyranoside (1), kaempferol 3-O-(6-trans
      caffeoyl)-beta-glucopyranosyl-(1-->2)-beta- glucopyranoside-7-O-alpha
      rhamnopyranoside (2), quercetin 3-O-(6-trans-p-coumaroyl)-beta-glucopyranosyl-(1-
      >2)-beta- glucopyranoside-7-O-alpha-rhamnopyranoside (3), and kaempferol 3-O-(6
      trans-p-coumaroyl)-beta-glucopyranosyl-(1-->2)-beta- glucopyranoside-7-O-alpha
      rhamnopyranoside (4), together with the known beta-3,4-dihydroxyphenethyl beta
      glucopyranoside were isolated. The structural elucidation of all compounds was
      deduced on the basis of 1H- and 13C-NMR spectral data, including those derived
      from 2D-NMR, as well as on HPLC-MS results.

PMID- 11345708
TI  - Identification of volatile constituents of Tambourissa leptophylla.
AB  - The volatile fraction of Tambourissa leptophylla fruit skin was extracted by
      petrol ether, purified by adsorption chromatography (LPC) and analysed by gas
      chromatographic-spectroscopic methods. 27 non-oxygenated terpene hydrocarbons and
      10 oxygenated derivatives were identified. The most abundant components were:
      limonene (24.0%), cis-alpha-bergamotene (23.2%), delta-3-carene (8.2%), alpha
      curcumene (6.0%), trans-alpha-bergamotene (5.1%), alpha-copaene (4.1%), alpha
      pinene (4.0%), p-cymene (4.0%) and bicyclogermacrene (3.3%). The crude volatile
      fraction was tested in vitro against Cladosporium cucumerinum in direct
      bioautography on TLC plates on the basis of the antifungal use of fruit skin.
      Activity of petrol ether extract against this micro-organism was demonstrated.

PMID- 11345709
TI  - On the absolute configuration of matricin.
AB  - The assignment of the absolute configuration of matricin rests on indirect
      evidence. On the basis of synthetic, NMR and CD studies with its decomposition
      product, chamazulene carboxylic acid, we were able to firmly establish the
      accepted 3S,3aR,4S,9R,9aS,9bS configuration of matricin.

PMID- 11345710
TI  - HPTLC method for the estimation of alkaloids of Cinchona officinalis stem bark
      and its marketed formulations.
AB  - We report a sensitive method for the estimation of quinine (Qn), cinchonine (Cn),
      and cinchonidine (Cnd) and a new method based on fluorescence enhancement and
      detection and quantification of quinidine (Qnd) from Cinchona stem bark and its
      formulations, using HPTLC. Standard solutions of Qn, Qnd, Cn, and Cnd were
      applied on precoated HPTLC plates and developed with chloroform/diethylamine
      (9.6:1.4 v/v). The plates were scanned and quantified at 226 nm for Qn, Cn, Cnd
      and for Qnd at 366 nm in fluorescence and reflectance mode ([symbol: see text]
      K400 filter). The method was validated for precision, accuracy and repeatability.
      Further, the stem bark of Cinchona officinalis and some herbal and homeopathic
      formulations were evaluated for their individual alkaloid content applying the
      developed method.

PMID- 11345711
TI  - The risk of haemorrhage associated with early postoperative heparin
      administration after intracranial surgery.
AB  - BACKGROUND: To analyse the rate of postoperative haemorrhage during a 4-year
      period of early postoperative administration (< 24 hours) of fractionated heparin
      plus compression stockings in a large cohort of patients undergoing intracranial
      surgery. METHOD: A total of 1564 patients who underwent intracranial surgery at
      our institution were included in our study. 1197 of the 1564 patients (77%) had
      major intracranial surgery (group 1). Group 2 was made up of 367 patients in whom
      ventriculoperitoneal shunting or external ventriculostomy was performed (minor
      intracranial procedures). All patients were investigated retrospectively for the
      occurrence of major postoperative haemorrhage confirmed by CT scanning and
      requiring surgical evacuation. The protocol for prophylaxis of thrombo-embolic
      events included early (< 24 hours) postoperative fractionated low-dose heparin (3
      x 5000 IE subcutaneously) until discharge plus intra- and postoperative
      compression stockings. FINDINGS: Major postoperative haemorrhages were observed
      in 31 of the 1564 patients (2.0%). In three patients, the haemorrhage occurred on
      the day of surgery before the administration of heparin. The haemorrhage rate of
      patients receiving heparin was 1.8% (28/1564). All haemorrhages occurred in
      patients undergoing major intracranial procedures (group 1; 31/1197; 2.6%). There
      was no haemorrhage in minor intracranial procedures (group 2; 0/367; 0%).
      INTERPRETATION: Although retrospective, this is to date the largest study
      supporting the concept of postoperative pharmacological thrombo-embolic
      propylaxis in patients undergoing intracranial surgery. The question as to
      whether pharmacological prophylaxis is beneficial for a given patient can only be
      answered by weighing the risk reduction of thrombo-embolic events against the
      risk increase of postoperative haemorrhage associated with different surgical
      procedures and heparin protocols.

PMID- 11345712
TI  - Risk control and quality management in neurosurgery. Munich October 15-18, 2000.

PMID- 11345713
TI  - Intraoperative measurement of arterial blood flow using a transit time flowmeter:
      monitoring of hemodynamic changes during cerebrovascular surgery.
AB  - BACKGROUND: The purpose of this study was to examine the utility and reliability
      of arterial flow measurements made with a transit time ultrasonic flowmeter for
      monitoring blood flow changes during intracranial and carotid surgery. METHOD: A
      total of 25 patients underwent intra-operative arterial blood flow measurements.
      The pulsatile flow curve and mean flow values were obtained using 1- to 6-mm
      transit time probes with a dual channel flowmeter. Four cases underwent aneurysm
      clipping, 11 cases superficial temporal artery (STA)--middle cerebral artery
      (MCA) bypass, 2 cases external carotid artery (ECA)--radial artery--MCA bypass
      for aneurysm trapping, and 8 cases carotid endarterectomy. In aneurysm clipping,
      blood flow in the branches distal to the aneurysm was measured before and after
      clipping. Blood flow in the STA was measured before and after STA-MCA
      anastomosis, and blood flow in the internal carotid artery (ICA) cervical portion
      was measured during carotid endarterectomy. Blood flow in the MCA and STA was
      monitored during radial artery grafting. FINDINGS: Blood flow in the STA was
      elevated after STA-MCA anastomosis. However, post-operative hyperperfusion
      syndrome was found in some cases whose flow elevation was over 50 ml/min. Also in
      one case of carotid stenosis, of which blood flow of ICA was elevated to 400
      ml/min after carotid endarterectomy, hyperperfusion syndrome was found after
      surgery. In the cases of MCA aneurysm clipping, decreasing of M2 flow was
      detected when clipping caused bifurcation stenosis. INTERPRETATION: We found
      transit time flow measurement useful for management of cerebrovascular surgery:
      the technique was simple to use and provided stable, reliable results. The method
      was able to reveal distal branch flow diminution in aneurysm clipping, or
      residual flow during temporary clipping in aneurysm surgery, and has the
      potential to predict post-operative complications such as hyperperfusion by
      signalling over-elevation of donor artery flow in bypass surgery or ICA flow in
      carotid surgery.

PMID- 11345714
TI  - Case reports of symptomatic metastases in four patients with primary intracranial
      gliomas.
AB  - Four patients with primary intracranial high-grade gliomas are reported. Three of
      them developed spinal symptoms and signs generated by spinal metastases a few
      months after first diagnosis, the last patient developed an extraspinal
      metastasis in cervical lymph nodes. The spinal metastasis of a 30 years old
      patient was located intradurally at L5/S1, in the second patient at level L3, the
      third patient presented with multiple metastases in the cervical, thoracic and
      lumbar spine. Previously reported cases are reviewed, are discussed in the light
      of our own observations and analysed for the various therapeutic options.

PMID- 11345715
TI  - Metastatic brain tumours from oesophageal carcinoma: neuro-imaging and
      clinicopathological characteristics in Japanese patients.
AB  - BACKGROUND: Since metastatic brain tumours from esophageal carcinoma are
      essentially rare, previous reports have not determined the common neuro
      radiological findings and its clinical aspects. FINDINGS: We report the neuro
      imaging and clinicopathological features of our 8 metastatic brain tumours from
      an esophageal site. Histologically, 6 of our 8 patients had squamous cell
      carcinoma and 2 had small cell carcinoma, a rare variant form. Both histological
      types mainly exhibited cystic lesions with a thin enhanced rim on magnetic
      resonance images (MRI, 4 of 6 squamous cell carcinomas and 1 of 2 small cell
      carcinomas). Combination therapy (irradiation and chemotherapy) after surgical
      treatment, the number of metastatic brain tumours, and the interval between their
      appearance and the diagnosis of the primary lesion could be prognostic factors in
      our series. INTERPRETATION: Among Japanese, the vast majority of primary
      esophageal cancers are squamous cell carcinomas. Therefore, MRI findings of a
      cystic tumour with a thin enhanced rim may alert one to the possibility of a
      metastatic brain tumour from the esophagus.

PMID- 11345716
TI  - Changes of cerebral blood flow following dexamethasone treatment in brain tumour
      patients. A Xe/CT study.
AB  - BACKGROUND: It is not exactly known how dexamethasone improves the function of
      brain that is affected by tumour. Whether and in what sense dexamethasone
      influences cerebral blood flow has rarely been addressed and previous
      investigations have yielded inconsistent results. METHOD: Stable xenon-enhanced
      computed tomography (Xe/CT) was used to assess the regional cerebral blood flow
      (rCBF) in 67 patients with supratentorial primary and secondary brain tumours.
      rCBF studies were done at least once prior to resection or stereotactic biopsy of
      the tumours. In nine patients repeated studies before surgery and in 15 patients
      additional studies after resective surgery were obtained. Dexamethasone was
      administered according to the clinical needs before surgery and systematically
      after surgery. Of the preoperative studies 30 were obtained before and 47 during
      dexamethasone treatment. The rCBF data were analysed upon correlations with daily
      dose, cumulative dose, and duration of dexamethasone treatment. Moreover,
      individual courses before and after surgery were examined. FINDINGS: Mainly
      inverse correlations were found between the treatment parameters, particularly
      the daily dose of dexamethasone, and rCBF. Only in the subgroup of glioblastoma
      patients, a positive correlation was found of both duration and cumulative dose
      of dexamethasone with rCBF in oedema. Serial observations of individual patients
      confirmed the above findings, yet with possible exceptions. After tumour
      resection a clear improvement of rCBF was regularly observed. INTERPRETATION: The
      beneficial effect of dexamethasone is not attributed to an increase of cerebral
      blood flow, because rather decreases of rCBF are mostly observed.

PMID- 11345717
TI  - Proton magnetic resonance chemical shift imaging (1H CSI)-directed stereotactic
      biopsy.
AB  - INTRODUCTION: To add metabolic information during stereotactic biopsy target
      selection, the authors adopted proton chemical shift imaging (1H CSI)-directed
      stereotactic biopsy. Currently, proton single voxel spectroscopy (SVS) technique
      has been reported in stereotactic biopsy. We performed 1H CSI in combination with
      a stereotactic headframe and selected targets according to local metabolic
      information, and evaluated the pathological results. PATIENTS AND METHOD: The 1H
      CSI-directed stereotactic biopsy was performed in four patients. 1H CSI and
      conventional Gd-enhancement stereotactic MRI were performed simultaneously after
      the fitting of a stereotactic frame. After reconstructing the metabolic maps of N
      acetylaspartate (NAA)/phosphocreatine (Cr), phosphocholine (Cho)/Cr, and
      Lactate/Cr ratios, focal areas of increased Cho/Cr ratio and Lac/Cr ratios were
      selected as target sites in the stereotactic MR images. RESULTS: 1H CSI is
      possible with the stereotactic headframe in place. No difficulty was experienced
      performing 1H CSI or making a diagnosis. Pathological samples taken from areas of
      increased Cho/Cr ratios and decreased NAA/Cr ratios provided information upon
      increased cellularity, mitoses and cellular atypism, and facilitated diagnosis.
      Pathological samples taken from areas of increased Lac/Cr ratio showed
      predominant feature of necrosis. CONCLUSION: 1H CSI was feasible with the
      stereotactic headframe in place. The final pathological results obtained were
      concordant with the local metabolic information from 1H CSI. We believe that 1H
      CSI-directed stereotatic biopsy has the potential to significantly improve the
      accuracy of stereotactic biopsy targeting.

PMID- 11345718
TI  - Alterations of norepinephrine levels in plasma and CSF of patients after
      traumatic brain injury in relation to disruption of the blood-brain barrier.
AB  - BACKGROUND: In injured brain tissue with a disrupted blood-brain barrier (BBB)
      catecholamines such as norepinephrine (NE) are known to enhance glucose
      consumption and cerebral blood flow but may lead to an energy depletion
      increasing the risk of ischemia. Therefore it is of great interest whether the
      exogenous administration of NE used mainly to maintain an adequate cerebral
      perfusion pressure influences CSF NE levels or not, and whether elevated plasma
      or CSF levels of NE can influence the actual clinical condition. We addressed
      this issue by measuring the levels of NE in CSF and plasma and correlating them
      with the actual clinical condition of the patients. METHODS: In 29 patients with
      severe TBI (< 8 points on the Glasgow Coma Scale, GCS) NE levels were analysed by
      high performance liquid chromatography (HPLC) in paired blood and CSF specimens
      which were collected from days 1 to 14 after severe TBI (total number of pairs =
      121). The integrity of the BBB was evaluated by determining the CSF/serum albumin
      ratio. The clinical condition of the patients was assessed by GCS. RESULTS:
      Elevated plasma and CSF NE levels were observed in 50% of all samples, most
      consistently in patients treated with NE. NE elevation in CSF was independent of
      whether or not the BBB remained intact. There was no correlation between GCS and
      the levls of NE in CSF or plasma either in samples from the treated or the
      untreated group. INTERPRETATION: Exogenous administration of NE seems to increase
      NE levels in plasma and CSF. However, in this group of patients with severe TBI
      there was no clinical evidence that exogenous administration of NE was
      detrimental to the traumatized patients.

PMID- 11345719
TI  - Cerebrospinal fluid from subarachnoid haemorrhage patients causes excessive
      oxidative metabolism compared to vascular smooth muscle force generation.
AB  - Cerebrospinal fluid (CSF) from subarachnoid haemorrhage (SAH) patients can
      stimulate vascular smooth muscle to generate force in vitro. CSF from SAH
      patients suffering from delayed ischaemic neurological deficits due to cerebral
      vasospasm can generate near maximal force in vitro and previous experiments have
      ascribed this generation of force to be a calcium mediated event. The
      intracellular calcium concentration has been demonstrated to rise during the
      vasospastic process. Calcium also stimulates oxidative metabolism as does
      adenosine diphosphate (ADP), the product of adenosine triphosphate (ATP)
      hydrolysis. Significant alteration in high energy metabolites such as ATP, ADP
      and phosphocreatine have also been demonstrated in various models of SAH mediated
      vasospasm. Vascular smooth muscle predominantly uses oxidative metabolism for
      force generation and reserves glycolytic metabolism for ion homeostasis. A
      decrease in oxidative metabolism during force generation would imply failing
      mitochondria and increased glycolytic high-energy phosphate supply. Increased
      oxidative metabolism would imply a decreased efficiency of the contractile
      apparatus or mitochondria. The aim of this study was to see if SAH CSF
      stimulation of porcine carotid artery oxidative metabolism was altered during
      force generation when compared with incremental calcium stimulation with
      potassium chloride depolarisation. CSF from patients (n = 10) who had
      subarachnoid haemorrhage stimulated force generation but with a significant
      'right shift' in oxygen consumption. This 'right shift' is indicative of an
      increased energy cost for contractile work. These results suggest that vascular
      smooth muscle contractile apparatus, when stimulated by subarachnoid
      cerebrospinal fluid, is consuming excess adenosine triphosphate during force
      generation.

PMID- 11345720
TI  - The stimulation of vascular smooth muscle oxidative metabolism by CSF from
      subarachnoid haemorrhage patients increases with Fisher and WFNS grades.
AB  - The purpose of this paper is to present an in vitro method for examining cerebral
      vasospasm after subarachnoid haemorrhage (SAH) which correlates to the patients'
      condition. The O2 consumption of the porcine carotid artery was monitored, using
      an oxygen electrode, after exposure to cerebrospinal fluid (CSF) from patients
      who had a SAH. The vessels were exposed to CSF from SAH patients at a 1 in 30
      dilution. Force measurements were carried out using freeze-dried CSF,
      reconstituted in the organ bath equivalent to undiluted CSF. These observations
      were then compared to the patients' condition. We divided the patient CSF samples
      into those that stimulated oxygen consumption above 0.4 microM/min/g dry wt, and
      those that did not. It was found that there was a correlation between the
      stimulation of oxygen consumption and the Fisher grade as well as the World
      Federation of Neurosurgeons Grading System (WFNS) for the patients. Of the CSF
      tested, 24 stimulated oxygen consumption above our cut off, and 8 did not (0.84
      +/- 0.34, n = 24 compared with the rate of 0.27 +/- 0.1 mumol/min/g dry wt,
      respectively; SD n = 8) at 180 minutes. We then examined the Fisher Grades of
      these two groups, the results were 3.21 +/- 0.88 vs 2.25 +/- 0.83 respectively
      (SD p < or = 0.01). When examining the WFNS System we found a similar difference
      between the groups that stimulated respiration and those who did not (WFNS Grades
      of 2.64 +/- 1.1 vs. 1.43 +/- 0.53; p < or = 0.01). The observed stimulation of
      oxygen consumption also correlated with tension generation in vitro. The CSF from
      subarachnoid haemorrhage patients stimulates the oxygen consumption of the
      porcine carotid artery. This stimulation correlated to the WFNS and Fisher Grades
      of the patients and can be performed using 1:30 dilution of CSF. We conclude that
      the metabolic changes that occur in the vessels during vasospasm are important
      parameters for assessing cerebral vasospasm.

PMID- 11345721
TI  - alpha-Phenyl-tert-N-butyl nitrone (PBN) improves functional and morphological
      outcome after cortical contusion injury in the rat.
AB  - alpha-Phenyl-tert-N-butyl nitrone (PBN), a potent reactive oxygen species (ROS)
      scavenger, has shown robust neuroprotective properties in several models of acute
      brain injury, although not previously evaluated in traumatic brain injury (TBI).
      In this study, we assessed the potential efficacy of PBN in a weight drop model
      producing a controlled cortical contusion. Sham operation, mild or severe injury
      was induced in intubated and ventilated rats and functional and morphological
      outcome was used as end-points at two weeks post-injury. In the trauma groups,
      saline or PBN (30 mg/kg) was injected as an intravenous bolus 30 minutes prior to
      injury. At day 11-15 post-injury, cognitive disturbance was assessed using the
      Morris Water Maze (MWM) and estimation of lesion volume and hemispheric loss of
      tissue was made. No change in MWM performance were found in either of the mildly
      traumatized groups as compared to uninjured controls. In contrast, a significant
      decrease in total mean latency and increase in path length in the severely
      traumatized rats were found. PBN-treatment significantly improved MWM performance
      as compared to saline treatment at the severe injury level (p < 0.05). The mild
      injury level caused a discrete atrophy of the ipsilateral cortex with no effect
      of PBN treatment. The severe injury caused a substantial loss of ipsilateral
      hemispheric tissue and a large cortical cavitation. PBN pre-treatment
      significantly reduced the lesion volume and reduced hemispheric loss of tissue at
      this injury level (p < 0.05). Our results support the involvement of ROS in the
      injury process contributing to the tissue loss and cognitive disturbance after
      TBI. The potential clinical utility of PBN will have to be assessed using a post
      injury dosing regime.

PMID- 11345722
TI  - A stereotactic device for experimental rat and mouse irradiation using gamma
      knife model B--technical note.
AB  - BACKGROUND: For radiobiological experiments using the Gamma Knife model B, we
      constructed a stereotactic device to irradiate rat and mouse brains and verify
      the absorbed dose at the target using thermoluminescence dosimetry and a head
      phantom. METHODS: Our stereotactic device is primarily designed for rats using
      the fixation principles of a stereotactic atlas. A head-fixation adapter for a
      mouse was constructed to enable targeted irradiation of mouse brains. We built
      simple phantoms to simulate rat and mouse heads. We placed thermoluminescent
      dosimeters at various positions on the phantom for dose measurements. Dose
      planning employed the Leksell Gamma Plan version 4.11 software, assuming a
      spherical skull geometry for all calculations. FINDINGS: The measurements
      demonstrated that the actual absorbed dose agreed with our calculations within
      the errors of thermoluminescence dosimetry and the accuracy of our irradiation
      technique and dose calculations. INTERPRETATION: This device provides an accurate
      method for irradiating rat and mouse brains using the Gamma Knife model B.

PMID- 11345723
TI  - Intervertebral disc calcification in childhood--a case report and review of the
      literature.
AB  - The authors report the case of a 10-year-old girl with intervertebral disc
      calcifications from the levels C6/C7 to Th1/Th2, presenting with a herniated
      calcified intervertebral disc at the C7/Th1 level, causing spinal cord
      compression with subsequent progressive paresis and sensory loss of her left leg.
      After anterior cervical discectomy and fusion the neurological deficits
      completely resolved within 2 weeks. It can be concluded that calcification of an
      intervertebral disc is a rare syndrome in childhood, causing progressive
      neurological deficit only in a few reported cases. Although the treatment of
      choice is conservative, surgery is required in patients who develop progressive
      neurological deficit.

PMID- 11345724
TI  - Decrease in intraoperative brain surface temperature in patients with
      subarachnoid haemorrhage.
AB  - BACKGROUND: Recent experimental and clinical evidence of hypothermic protection
      against neuronal injury creates new interests regarding human brain temperature.
      However, very little information is available for the brain temperature under
      certain pathological conditions. In this study, intra-operative brain temperature
      in patients with subarachnoid haemorrhage (SAH) is particularly addressed.
      METHODS: Brain surface temperature and oxygen saturation of jugular bulb (SjO2)
      were monitored during early surgery undergone within 48 hours after the onset in
      patients with SAH (n = 16). Those were also measured in patients with unruptured
      aneurysms during elective surgery as control (n = 15). FINDINGS: The brain
      surface temperature was significantly lower in SAH than control (35.3 +/- 0.8 vs.
      36.1 +/- 0.5 degrees C, P < 0.01). The reduction in brain surface temperature was
      correlated with the severity of the Hunt and Kosnik's aneurysmal grade (r =
      0.837, P < 0.01). SjO2 was significantly lower in SAH than control (51.5 +/- 7.3
      vs. 68.5 +/- 7.6%, P < 0.01), and was positively correlated with brain surface
      temperature (r = 0.642, P < 0.01). INTERPRETATION: These results suggest that the
      brain temperature and/or the temperature gradient within the brain may be altered
      in an early period after SAH. Since brain temperature is determined by cerebral
      blood flow (CBF), metabolism, temperature of both circulating blood and
      surrounding environment, the brain surface temperature reduction may be explained
      by depressed CBF and metabolism in SAH.

PMID- 11345725
TI  - Pseudoaneurysm of the intracavernous carotid artery following endoscopic
      endonasal transsphenoidal surgery, treated by endovascular approach.

PMID- 11345726
TI  - Symptomatic arachnoid diverticulum within temporal lobe.

PMID- 11345727
TI  - State of the Association address.

PMID- 11345728
TI  - Clinicopathologic correlation quiz: mixed radiolucent-radiopaque lesions
      associated with teeth.

PMID- 11345729
TI  - The resin retained natural tooth pontic: a transitional esthetic solution.
AB  - This case report presents an alternative treatment option for the premature loss
      of a maxillary anterior tooth due to severe periodontitis. A natural tooth pontic
      acid-etch prosthesis was fabricated using the patient's clinical crown from the
      extracted tooth. This measure proved to be a very adequate, esthetic treatment
      solution before a permanent restorative plan could be developed for the patient's
      long term dental needs.

PMID- 11345730
TI  - Meet your new ADA sixth district trustee, an interview with Dr. William D. Powell
      by Dr. Gerald R. Karr.

PMID- 11345731
TI  - Development and validation of a dynamic mathematical model of ammonia release in
      pig house.
AB  - A dynamic mathematical model of Carbon-dioxide Accelerated Ammonia Release (CAAR)
      was developed based on the known knowledge of the chemistry of ammonia (NH3) in
      liquid solution, mass transfer inside liquid and across liquid-gaseous interface,
      and a new concept of CAAR. It calculated the NH3 concentration, release and
      emission at transient and steady state conditions related to a mechanically
      ventilated pig house. One field experimental data set was used for estimating the
      proportionality coefficient in the model. Another field data set was used for
      model validation. The ammonia concentration and emission rate calculated in the
      model validation were compared with the field measurement values. R2 of 0.861 and
      0.947 were obtained for NH3 concentration and emission rate, respectively. In the
      model validation, the pH in manure surface was found to increase from 8 at
      initial condition to 8.85 at dynamic equilibrium due to the co-release of CO2
      from the manure. This pH change accelerated the NH3 release by 6.1-fold. The
      model provided a quantitative description of some new understanding of the
      mechanism of NH3 release in the pig house and entailed suggestions of two new
      techniques of NH3 emission abatement: the reduction of CO2 release and the new
      ventilation control strategy.

PMID- 11345732
TI  - Pb, Zn, and Cu levels in tree barks as indicator of atmospheric pollution.
AB  - Barks of seven species of trees were sampled at 32 locations having different
      pollution levels in Abeokuta, Nigeria. The concentrations of Pb, Zn, and Cu were
      determined by atomic absorption spectrometry. The Pb and Zn contents, 1.9-159.8
      and 16.5-659.1 micrograms g-1, dry weight respectively, correlate with traffic
      volume, indicating pollution from anthropogenic sources. The results obtained for
      Cu, 4.2-20.7 micrograms g-1, dry weight, though lower, were still significant but
      did not show any correlation with traffic density. The study also confirms the
      suitability of Azadirachta indica (Dogoyaro--a very popular local tree) as a
      suitable bio-indicator of aerial fallout of heavy metals.

PMID- 11345733
TI  - Upgrading the conventional grease trap using a tube settler.
AB  - Grease traps are widely used by most restaurants and food processing industries
      in Hong Kong to reduce oil and grease to an acceptable level before it can be
      discharged to public sewers. To meet demanding effluent standards in the future,
      it is necessary to polish the effluent by upgrading the conventional trap design.
      This study evaluated the possibility of upgrading traditional grease traps by
      installing tube settlers inside the trap. Their efficiency of removing chemical
      oxygen demand (COD) and oil/grease was examined to justify the performance. It
      was found that installing a tube settler is a feasible and cheap way to upgrade
      the conventional grease trap, since it improved oil/grease removal efficiency by
      8-10% compared to the conventional design. In addition, a remarkable improvement
      in COD removal was observed following a very short hydraulic detention time after
      the installation of tube settlers. This ensured acceptable effluent quality under
      peak flowrates. Two mathematical models were also proposed to facilitate trap
      design.

PMID- 11345734
TI  - Determination of organic micropollutants in rain water for laboratory screening
      of air quality in urban environment.
AB  - Rain water may collect organic air pollutants, such as polycyclic aromatic
      hydrocarbons (PAHs), phthalate ester (PEs), pesticides, and polychrorinated
      biphenyls (PCBs), that could be present in air in consequence of different
      factors. The determination of these compounds in rain water samples consequently
      may be interesting for a first screening of air quality in urban and/or
      industrial areas. For this purpose, 3 areas of the city of Rieti (central Italy)
      were selected for rain water sampling: a) the city center, densely populated and
      with high road traffic; b) a suburban residential area; c) the industrial area,
      about 3 km out of the city center and along the state road. Wet-only
      precipitation collectors were used for sampling; solid-phase microextraction or
      liquid-liquid microextraction techniques followed by GC/MS determinations were
      applied for sample analysis. PCBs and pesticides were never found in the samples
      collected. On the contrary, some polycyclic aromatic hydrocarbons and phthalates
      were always found. Significant and seasonal differences in PAH levels were
      observed in the 3 different sampling areas, with higher values always found in
      the city center and during the winter period; on the contrary, PEs levels
      remained unchanged.

PMID- 11345735
TI  - Spatial and temporal variability of composition of urban effluents in the island
      of Lesvos, Greece.
AB  - The spatial and temporal variability in the composition of effluents of the
      coastal town of Mytilene, island of Lesvos, Greece, was investigated in 8 sewers
      of the town. Differences were found in the quality of effluents between the old
      and new parts of the town and were attributed mainly to the different design and
      construction of the sewers, as well as to the occasional discharge of septage
      into the sewerage network in parts of the town. During summer the population and
      water consumption increase, leading to partial dilution of the organic load.
      However, in the same period (July), the concentrations of dissolved Zn and
      particulate Pb were enriched. The reasons for such an increase are not clear. At
      present the seasonal metal peaks (Pb and Zn) are attributed to the increased
      traffic (Pb and Zn) and to increased corrosion under the prevailing weather
      conditions of the water supply network, which includes a very large number of
      galvanized storage tanks (Zn).

PMID- 11345736
TI  - Human exposure to PCDD/Fs in the UK: the development of a modelling approach to
      give historical and future perspectives.
AB  - In order to assess the long-term impact of persistent organic contaminants such
      as polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs)
      it is important to be able to quantify historical exposure. An understanding of
      past exposure is not only important to place our current body burdens in
      perspective, but is useful in assessing our potential future exposure.
      Unfortunately, very few direct measurements of our main source of exposure (i.e.,
      food) over the past decades are available. This study attempts to reconstruct the
      historical exposure of the UK population to PCDD/Fs using a combination of
      emission estimates, information on environmental temporal trends derived from
      sediment cores and archived materials, and environmental/human fate modelling.
      Predicted adipose and blood lipid concentrations for a typical cross section of
      the population are derived over time (1920-2000), which is compared with measured
      data. The approach has been tested with two PCDDs and two PCDFs and showed
      encouraging agreement with measured data. Certain parts of the modelling
      methodology have been highlighted where there is still poor understanding of the
      processes governing fate and behaviour. These areas are discussed and
      recommendations for future improvements are made. The paper thus represents an
      initial modelling approach which defines both the historical (1920-present) and
      future (present-2020) fate of PCDD/Fs in the UK population.

PMID- 11345737
TI  - Particle size distribution and its elemental composition in the ambient air of
      Delhi.
AB  - This study examines the chemical composition of PM10, the thoracic fraction of
      the atmospheric particulate matter. An eight-stage Anderson impactor is used to
      separate the PM10 from other fractions with different aerodynamic behaviour at
      three different area representative sites in Delhi from February to May 1998.
      PM10 particulate are subdivided into two fractions, coarse (> 2.1-10 microns) and
      fine (< 2.1 microns). The concentrations of major heavy metals such as Pb, Zn,
      Cd, Ni, and Fe are determined by atomic absorption spectrophotometer. The average
      concentration of coarse fraction of PM10 is found to be 68.3 +/- 17 micrograms/m3
      while the fine fraction of PM10 is 71.3 +/- 15 micrograms/m3 for Delhi. Metal
      concentration (except Fe) in fine fraction exceeds by a factor of up to 6, as
      compared to that in the coarse fraction. In order to identify the major sources
      of fine and coarse fraction of PM10, principle component analysis (PCA) was
      undertaken and three major sources were identified, namely vehicular emissions,
      industrial emission, and soil resuspension.

PMID- 11345738
TI  - Evaluation of some air pollution indicators in Turkey.
AB  - This article intends to shed a light on air quality in Turkey and compare air
      pollutant emissions on a national scale with that of the European countries. In
      order to estimate the quantities of Turkish emissions in the past and their
      future predictions, a national emission inventory was prepared with respect to
      five major pollutants consisting of particulate matter(PM), SOx, NOx, non-methane
      volatile organic compounds, and CO with 5-year intervals between 1985 and 2005.
      The results suggest that Turkey is a rather large emission source at the European
      scale, although emission indicators on unit area and per capita were shown to be
      somewhat smaller in magnitude. Levels of air pollution in some of the big cities
      in Turkey were also evaluated from available national monitoring data. These
      evaluations for the urban air qualities covered SO2 and PM parameters between
      1986 and 1996, and results were compared with the present Turkish air quality
      limits, their probable revisions, WHO (Europe) guidelines and related EC
      directives. Results showed that the air quality limits were not met, especially
      during the winter periods in Turkish cities. Urban air pollutants characterizing
      the air in Turkish cities other than SO2 and PM, however, could not have been
      evaluated as these pollutants were not systematically monitored in these cities.

PMID- 11345739
TI  - Sulfate and chloride concentrations in Texas aquifers.
AB  - Median sulfate and chloride concentrations in groundwater were calculated for 244
      Texas counties from measurements at 8236 water wells. The data were mapped and
      analyzed with a geographic information system (GIS). Concentration clusters for
      both solutes were highest in north-central, west, and south Texas. Thirty-four
      counties had median sulfate levels above the secondary standard of 250 mg/L, and
      31 counties registered median chloride concentrations above 250 mg/L. County
      median concentrations ranged from < 1.5 to 1,953 mg/L for sulfate, and from 6 to
      1,275 mg/L for chloride. Various factors contribute to high sulfate and chloride
      levels in Texas aquifers, including mineral constitutents of aquifers, seepage of
      saline water from nearby formations, coastal saltwater intrusion, irrigation
      return flow, and oil/gas production. Ten counties in central and northeast Texas
      lack data and warrant additional monitoring.

PMID- 11345740
TI  - Investigation of a ponding irrigation system to recycle agricultural wastewater.
AB  - This article presents the results of natural carrying capacity of ponding
      irrigation system in Taoyuan agricultural zone, Taiwan. Both the systematic water
      quality and the ponding effects were examined. The ponding irrigation system
      included a flow channel and storage ponds. The data showed that most water
      characteristics deteriorated gradually from upper- to down-stream in the flow
      channel and the flow channel was not attributed to any self-purification in
      agricultural returning water practically. On the other hand, the results of
      storage ponds indicated that they can provide a natural treatment (i.e., the
      outlet water quality of the ponds is more desirable than that of the inlet).
      Consequently, the ponding irrigation system offers the natural self-purification
      in ponds to reuse and recycle the returning agricultural wastewater and to extend
      the irrigation capacity and efficiency.

PMID- 11345741
TI  - Dissolution of 226Radium from pipe-scale deposits in a public water supply.
AB  - This study was undertaken to determine if dissolution of 226Radium from pipe
      scale deposits contributes to enhanced waterborne 226Radium concentrations at the
      point of use. Water samples were collected from residential water customers of a
      small rural Iowa town. Sites were evenly divided between new and old water main
      connections. Daily samples were collected from the point-of-entry water. Point-of
      use 226Radium concentrations ranged from 0.4 to 12.9 pCi L-1 (0.01 to 0.5 Bq L
      1). The mean 226 Radium concentration for homes connected to old water mains was
      significantly higher than the mean 226Radium concentration of homes connected to
      new water mains, mean(standard deviation) equal 8.3(1.1) and 5.3(0.8) pCi L-1
      [0.3(1.1) and 0.2(0.8) Bq L-1], respectively. 226Radium concentrations of the
      point-of-entry water ranged from 5.0 pCi L-1 to 10.3 pCi L-1 (0.2 Bq L-1 to 0.4
      Bq L-1). This study indicates considerable variability of 226Radium exposure from
      drinking water among residents of the same water supply and has implications for
      regulatory compliance and exposure assessment in epidemiologic studies.

PMID- 11345742
TI  - Decolorization of Remazol Black-B using a thermotolerant yeast, Kluyveromyces
      marxianus IMB3.
AB  - The ability of Kluyveromyces marxianus IMB3 to decolorize Remazol Black-B dye was
      investigated. The effect of environmental conditions, such as pH and temperature
      were examined. No noticeable effects on decolorization were observed when pH
      varied from 3.0-5.5. Maximum colour removal, 98%, was achieved at 37 degrees C.
      Little or no colour removal was detected when K. marxianus IMB3 was incubated
      under anaerobic conditions. Further investigation, in which decolorization was
      monitored under extreme temperatures and low pH (to inhibit growth) and using ten
      fold dense inoculum, revealed that decolorization was due to biosorption to the
      yeast cells and not due to a metabolic reaction.

PMID- 11345743
TI  - Sources of air pollution due to coal mining and their impacts in Jharia
      coalfield.
AB  - Indian coal consumption is about 5.5% of the world and the share of coal as
      energy went up to 66%. The increasing trend of opencast coal mining lead to
      release of dust and gaseous pollutants. The Indian reserve of coking coal is
      mainly located in Jharia coalfield and having reserves upto a depth of 1219m are
      19339 Mt. The coalfield is subjected to intensive mining activities and accounts
      for 30% of the total Indian coal production. Coal mining in Jharia coalfield and
      the sources of air pollution along with the production of air pollutants have
      been described. The dust particles act as centres of catalysis for many of the
      chemical reactions taking place in the atmosphere. Characteristics and effects of
      the pollutants have been discussed. An estimate of the dust generated and
      discharged into the atmosphere can be made by using emission factor or prediction
      type equations. It is disirable that this exercise is to be undertaken in
      planning stage so that adequate and appropriate mitigating measures can be
      incorporated into the project at least cost.

PMID- 11345744
TI  - Study of water quality of Hudiara drain, India-Pakistan.
AB  - This paper examines the extent of pollution in Hudiara drain water due to
      untreated industrial and sewage waste of India and Pakistan. Ninety-nine surface
      water samples from the Pakistani side of the Hudiara drain were collected during
      September 1997, and April and June 1998. The analytical results of the Hudiara
      drain samples point out the industrial and sewage inputs from India and Pakistan.
      Higher values of biochemical oxygen demand (BOD), chemical oxygen demand(COD),
      total organic carbon(TOC), and trace metals in drain samples from the Indo-Pak
      border clearly indicate the Indian industrial and sewage pollution. Large
      variations in the levels of various measured parameters (COD, BOD, TOC, pH, total
      soluble substances, and trace metals) were observed along the Hudiara drain in
      the Pakistani vicinity. These variations were due to different types of
      industrial effluents and small village drains. The study showed that suspended
      solids(SS), COD, and fecal coliform (FC) were the major pollutants. Accordingly,
      the most feasible alternative is to convert the drainage network to a
      sedimentation and temporary storage reservoir. If disinfected, the runoff water
      can be used for restricted irrigation. Groundwater samples taken from the drain's
      surrounding area have also been analyzed. Thirty percent of the samples are not
      fit for drinking purposes due to NO3-N, Se and FC counts as prescribed by World
      Health Organization (WHO) guidelines. A trilinear diagram clearly indicates the
      influence of surface water of the Hudiara drain on ground water; moreover, higher
      values of nitrate and FC clearly indicate the seepage from the Hudiara drain.

PMID- 11345745
TI  - A new concept of carbon dioxide accelerated ammonia release from liquid manure in
      pig house.
AB  - Indoor air quality in animal buildings is very important to the health of
      agricultural workers and animals. Carbon dioxide (CO2) and ammonia (NH3) are two
      of the most important pollutants in pig houses. Four tests were conduced in a
      mechanically ventilated pig house to study release behaviors of CO2 and NH3 from
      liquid manure using impulse, pulse and step ventilation inputs. The CO2 and NH3
      concentrations were sampled in the exhaust chimney and measured with a CO2
      monitor and a NOx analyzer, respectively. The ventilation rate was measured with
      a ventilation rate sensor in the chimney. A new phenomenon, characterized by a
      delayed dynamic response of NH3 release to the high ventilation inputs as
      compared with the response of CO2 release, was encountered. A new CO2 factor was
      identified as the cause of the delayed NH3 response. An original concept of
      Carbon-dioxide Accelerated Ammonia Release (CAAR) was developed. It explained
      that, at the initial stage of gas release induced by the high ventilation, the
      high release of CO2 gradually raised the pH in the surface manure. The increased
      pH accelerated the release of NH3. The higher release of NH3 had a negative
      feedback to the pH. The effects of CO2 and NH3 releases on the pH finally reached
      a dynamic equilibrium. The NH3 release under the dynamic equilibrium was greatly
      accelerated compared to that under initial conditions.

PMID- 11345747
TI  - [The influence of N-nitro-L-arginine methyl ester (L-NAME) on hydroxyl free
      radical formation in the post-ischemic reperfused heart of anesthetized rats].
AB  - N-nitro-L-arginine methyl ester (L-NAME) has been reported to have protective
      action against hydroxyl free radicals. We have investigated whether L-NAME
      influences free radical formation in the post-ischemic reperfused heart of
      anesthetized rats. An isolated rat heart-lung preparation was used. Forty male
      Wistar rats were allocated into D (D-NAME 100 microMol.l-1), L (L-NAME 100
      microMol.l-1), LH (L-NAME 100 microMol.l-1 and 1MAC halothane), LI (L-NAME 100
      microMol.l-1 and 1MAC isoflurane), and LS (L-NAME 100 microMol.l-1 and 1MAC
      sevoflurane) groups. The heart was perfused initially at the cardiac output of 30
      ml.min-1 and the atrial pressure of 70 mmHg. Drugs were administered into the
      reservor 7 min after the start of perfusion. Ten minutes after the start of
      perfusion, the heart was rendered globally ischemic for 10 min by reducing the
      preload and afterload to zero and then reperfused for 10 min. At the end of
      reperfusion, the heart was freeze-dried for 4 days. The perfusate blood was
      collected just before and after ischemia and at the end of reperfusion. The
      formation of hydroxyl radicals in the perfusate blood and heart was measured with
      high-performance liquid chromatography using salicylic acid. Hydroxyl radicals
      react with salicylic acid, yielding dihydroxybenzoic acid (DHBA). Before and
      after ischemia, there were no significant differences among the groups in cardiac
      output, systolic pressure, heart rate, and right atrial pressure. DHBAs in the
      heart of L, LH, LI, and LS groups were significantly lower than those of D group.
      However, there were no differences in the DHBA levels among 4 groups. The
      concentrations of DHBA in the perfusate blood after ischemia and reperfusion were
      significantly higher than those before ischemia in all groups. DHBAs in the
      perfusate blood after ischemia and reperfusion of L, LH, LI, and LS groups were
      significantly lower than those of D group. However, there were no differences in
      the DHBA levels among 4 groups administered L-NAME. This study indicates that L
      NAME reduces hydroxyl free radical formation in the post-ischemic reperfused
      heart in anesthetized rats and volatile anesthetics do not influence the
      depressant effect of hydroxyl free radical formation by L-NAME.

PMID- 11345746
TI  - [The effects of milrinone on hemodynamics in patients undergoing cardiac
      surgery].
AB  - The phosphodiesterase inhibitor, milrinone is used to treat low cardiac output
      syndrome, especially after cardiac surgery. But there were few reports about the
      precise hemodynamic effects at separation from cardiopulmonary bypass (CPB). We
      examined the hemodynamic effects of milrinone in 24 patients undergoing elective
      coronary artery bypass graft (CABG). Patients were assigned to the milrinone
      group (n = 12) and the control group (n = 12). Before separation from CPB,
      milrinone was administered as a loading dose of 50 micrograms.kg-1 into the
      reservoir of CPB at rectal temperature 33.5 degrees C and simultaneously a
      continuous infusion of 0.5 microgram.kg-1.min-1 was started. In addition,
      dopamine and nitroglycerine were administered in both groups. Hemodynamic
      measurements were performed before CPB, just after the weaning from CPB, 15, 30,
      60 minutes after the weaning from CPB. Cardiac index increased significantly (P <
      0.01) in the milrinone group as compared with the control group. Systemic
      vascular resistance index and mean arterial pressure decreased significantly (P <
      0.0001, P < 0.05, respectively) in the milrinone group as compared with the
      control group. There were no significant differences in heart rate, mean
      pulmonary arterial pressure, pulmonary artery occlusion pressure, mean right
      atrial pressure, stroke volume index, and pulmonary vascular resistance index
      between the two groups. These hemodynamic effects showed that milrinone supported
      cardiac performance after CPB for CABG.

PMID- 11345748
TI  - [Recovery characteristics of propofol anesthesia in pediatric outpatients;
      comparison with sevoflurane anesthesia].
AB  - We compared recovery characteristics of propofol anesthesia with those of
      sevoflurane anesthesia in pediatric outpatients. One hundred and four children, 3
      months to 6 years of age, ASA physical status 1 or 2, were randomly assigned to
      following four groups; sevoflurane (group S), propofol (group P), sevoflurane
      with premedication (group MS), or propofol with premedication (group MP).
      Midazolam 0.5 mg.kg-1 and famotidine 1 mg.kg-1 were administered orally 30 min
      before the induction in the MS and MP group. Recovery from anesthesia, agitation,
      and postoperative pain were evaluated. The time intervals from the end of surgery
      to extubation and to discharge from the hospital were recorded. The incidence of
      vomiting and use of analgesic drugs were also checked. The emergence from
      anesthesia was slower with propofol anesthesia than with sevoflurane anesthesia,
      but the time to discharge from the hospital was not significantly different among
      the four groups. Incidence of agitation was higher in S group compared with P
      group, but there were no differences between MS and MP. Postoperative pain was
      similar among the four groups. There were no differences in the incidence of
      vomiting. Propofol anesthesia provided slower emergence and less agitation
      compared with sevoflurane anesthesia.

PMID- 11345749
TI  - [The effect of the decreased serum concentration of propofol induced by rapid
      fluid infusion on the spectral edge frequency 90 and median frequency].
AB  - The effect of decreased serum concentration of propofol induced by rapid infusion
      therapy on the EEG was assessed by spectral edge frequency 90% (SEF90) or median
      frequency (MF) during propofol anesthesia. The eight scheduled surgical patients
      were administered propofol with a constant rate, and the rapid infusion therapy
      with 10 ml.kg-1 of acetate Ringer's solution significantly decreased the serum
      concentration of propofol from 1.96 +/- 0.22 micrograms.ml-1 to 1.68 +/- 0.19
      micrograms.ml-1 (approximately 17% reduction). Simultaneous monitoring of SEF90
      and MF, however, demonstrated no change during investigation. These results
      suggest that the mild decrease of the concentration of propofol might not induce
      the significant change of EEG, or that the reduction of propofol concentration by
      infusion might be deceptive and produce no significant change in the
      concentrations of each pharmacological compartment.

PMID- 11345750
TI  - [Changes in sedative level during induction of anesthesia using a single volatile
      anesthetic].
AB  - We investigated the changes in sedative level during induction of anesthesia
      using a single volatile anesthetic, sevoflurane, compared with the changes when
      propofol and sevoflurane were used. We used a bispectral index (BIS) monitor
      (Aspect, Newton, USA) to monitor the sedative level. Thirty patients were
      randomly divided into one group receiving sevoflurane alone (S group, n = 15) and
      another group receiving propofol and sevoflurane (PS group, n = 15). The S group
      received 5% sevoflurane with nitrous oxide 6 l.min-1 and oxygen 3 l.min-1 via a
      face mask, while the PS group received propofol 1.5 mg.kg-1 i.v. followed by step
      wise increasing sevoflurane up to 5%. Induction times, as assessed by loss of
      eyelash reflex, were 32 s in the PS group and 65 s in the S group. The decrease
      in the BIS value was smooth in the S group, whereas it increased transiently and
      varied greatly in the PS group. Two patients in the PS group showed body movement
      during induction of anesthesia, and the BIS values in both cases transiently
      exceeded 60. BIS monitor is useful for monitoring the sedative level during
      induction of anesthesia, and induction using a single volatile anesthetic such as
      sevoflurane is smooth.

PMID- 11345751
TI  - [Do all patients with mandibular hypoplasia present difficulty in endotracheal
      intubation?].
AB  - On 7 patients with Pierre-Robin syndrome (PR), 8 patients with first and second
      brachial arch syndrome (BA) and 7 patients with Treacher Collins syndrome (TC),
      we examined retrospectively the number of patients whom anesthesiologists found
      difficult to perform laryngoscopy and intubation, the number of attempt necessary
      for proper insertion of the tracheal tube, the number of patients in whom the
      endotracheal intubation with laryngoscopy was given up and the time necessary for
      endotracheal intubation. We compared these with those from 22 control patients.
      Our results suggest that the difficult laryngoscopy and intubation are more
      frequent in TC. On the other hand, most of PR and BA may not present difficulty
      in intubation.

PMID- 11345752
TI  - [Anesthetic management of the King-Denborough syndrome].
AB  - The King-Denborough syndrome (KDS) is a congenital myopathy with musculoskeletal
      abnormalities, and definitely associated with susceptibility to malignant
      hyperthermia (MH). We present the first report in Japan concerning the management
      of a KDS patient. A 2-year-old boy was scheduled for cryptorchidopexy. He had
      some physical signs of KDS, e.g. pectus excavatum, low-set ears, malar
      hypoplasia, micrognathia, ptosis and down-slanting palpebral fissures. Moreover,
      his mother and maternal grand-uncle had medical history of MH. Therefore, he was
      diagnosed as KDS by pediatricians. All of the preoperative examinations,
      including serum creatine phosphokinase level, are normal. Previous 15 case
      reports suggest that in KDS patients MH might be triggered by volatile
      anesthetics. To avoid the trigger, we maintained the general anesthesia with
      propofol, fentanyl and vecuronium. During perioperative period, his body
      temperature was 36.3-38.1 degrees C, and no symptom of MH was observed. It is
      rare that a diagnosis of KDS is made preoperatively since the MH-induction is
      involved in the criteria of this syndrome. In the anesthesia of patients who are
      suspected of KDS from their characteristic features or familial histories, an
      anesthesiologist should pay attention to prevent MH. The total intravenous
      anesthesia method appears useful for the management of KDS.

PMID- 11345753
TI  - [Perioperative management of twins with prenatally diagnosed congenital
      diaphragmatic hernia].
AB  - Congenital Diaphragmatic Hernia (CDH) occurs in one of every 2000-3000 births,
      and most of them are sporadic, and therefore recognized as a circumstantial
      event. But its occurrence in 85 children among the 40 families is also reported,
      and some reports suggest that an autosomal recessive gene may be responsible for
      this disease. We experienced identical twins (babies A and B) both with
      prenatally diagnosed CDH. They were delivered by emergent cesarean section at 33
      weeks of gestation with birth weight of 1857 g and 1561 g, respectively. They
      were intubated immediately after birth, and ventilated with high frequency
      oscillation. Baby A presented persistent pulmonary hypertension of newborn, and
      received nitric oxide inhalation. At the age of 2 days, both of them were
      stabilized and underwent repair of CDH. After the repair, baby A developed
      perforation of ileum, airway bleeding and retinopathy of prematurity (ROP), and
      needed 28 days before extubation. Baby B also developed ROP, but had no other
      problem, and the trachea was extubated at the age of 12 days. They are the
      seventh pair reported in the world literature.

PMID- 11345754
TI  - [Anesthetic management of parturients with Marfan syndrome].
AB  - Ten pregnancies and 7 deliveries in 5 patients of Marfan syndrome were managed at
      our institution. Three patients were delivered with a cesarean section under
      general anesthesia, and one was delivered under epidural anesthesia. Three
      underwent vaginal delivery with epidural anesthesia. Two patients selected
      induced abortion, and one had a spontaneous abortion. Six of 7 neonates and all 5
      mothers survived without any sequela. One had intrauterine fetal death due to
      dissection of aortic aneurysm. Simultaneous cesarean section and cardiovascular
      operation under cardiopulmonary bypass were performed in one case. In the
      parturient without progress of cardiovascular complication during pregnancy,
      painless labor under epidural anesthesia is our first choice to minimize
      hemodynamic derangement. Invasive arterial blood pressure and central venous
      pressure were monitored in all cases of vaginal delivery for tight hemodynamic
      control. Epidural anesthesia is also preferred in cases of elective cesarean
      section for obstetric indication. Emergency cesarean sections are performed in
      the cases of progressive dissection and urgent obstetric indication. General
      anesthesia was induced with fentanyl and midazolam to minimize cardiovascular
      response to tracheal intubation. We emphasize that evaluation of cardiovascular
      status and multidisciplinary approach are the key in the anesthetic management of
      parturients with Marfan syndrome.

PMID- 11345755
TI  - [Co-administration of nitrous oxide reduces the pressor response against oro
      tracheal intubation during induction of anesthesia with propofol infusion at a
      low rate].
AB  - This study investigated the effect of co-administration of nitrous oxide on the
      cardiovascular changes during induction of anesthesia with propofol infusion at a
      low rate. Sixty patients undergoing general anesthesia were randomly allocated
      into two groups, and received the inhalation of 100% oxygen (group 1) or 60%
      nitrous oxide and oxygen (group 2) via face mask for 3 minutes before
      administration of propofol at 15 mg.kg-1.hr-1. After beginning of propofol
      infusion, patients inhaled each gas continuously and the loss of response to
      simple commands by the anesthesiologist was considered as hypnosis. The dose and
      time for achieving hypnosis were determined, and non-invasive blood pressure,
      heart rate and arterial oxygen saturation were recorded during induction of
      anesthesia. Cardiovascular changes during induction were not different between
      the two groups except mean and diastolic blood pressure immediately after oro
      tracheal intubation [126 +/- 21 vs. 113 +/- 21 mmHg and 108 +/- 21 vs. 95 +/- 19
      mmHg, respectively (mean +/- SD)]. The dose of propofol and the time for
      achieving hypnosis showed no significant difference (73 +/- 20 vs. 68 +/- 19 mg
      and 4.8 +/- 1.0 vs. 4.4 +/- 1.0 min, respectively). Almost all patients were
      sedated with inhalation of nitrous oxide before infusion of propofol, but no
      additive effect was observed with nitrous oxide and propofol. Co-administration
      of nitrous oxide during propofol infusion at a low rate was an effective method
      to avoid undesirable pressor responses against oro-tracheal intubation without
      causing adverse cardiovascular depression.

PMID- 11345757
TI  - [Pseudohypoxemia in a patient with chronic myeloid leukemia and splenomegaly].
AB  - A 35-year-old man with chronic myeloid leukemia whose peripheral leukocyte count
      was 18.6 x 10(4).mm-3 underwent splenectomy. Perioperative arterial blood gas
      analysis showed lower oxygen saturations than those measured with pulse oximetry.
      The findings suggested pseudohypoxemia because of marked leukocytosis.

PMID- 11345756
TI  - [Ketamine lollipop for pediatric premedication].
AB  - Lollipop containing ketamine (50 mg) was evaluated for the premedication of
      pediatric patients. The subject of this study were 12 children aged from 1 year 7
      months to 6 years. They received the lollipop and showed relatively good
      emotional state and no typical side effects. These results suggest good
      possibility of ketamine lollipop as the premedication for pediatric patients.

PMID- 11345758
TI  - [Recurrence of bullous pemphigoid after surgery: report of a case].
AB  - We report a 38-year-old woman with myoma uteri and bullous pemphigoid controlled
      by oral prednisolone (7.5 mg.day-1). She underwent transabdominal hysterectomy
      under epidural anesthesia using mepivacaine supplemented with intravenous
      midazolam and butorphanol, without untoward event. On the postoperative day 2,
      recurrence of bullous pemphigoid was noted. The skin lesion of pemphigoid was
      improved after increasing the prednisolone dose up to 60 mg a day.

PMID- 11345759
TI  - [A case of suspected pulmonary air embolism in endoscopic neurosurgery].
AB  - Sudden reduction in end-tidal PCO2 and SpO2 occurred during the endoscopic third
      ventriculostomy in a patient with hydrocephalus under general anesthesia. We
      suspect that it was caused by pulmonary air embolism. A 63-year-old female was
      scheduled for endoscopic third ventriculostomy under general anesthesia.
      Endoscopic manipulation caused hemorrhage from chorioid plexus 21 minutes after
      the procedure was begun, and intraventricular irrigation was performed to achieve
      hemostasis. In the subsequent 3 minutes, end-tidal PCO2 declined from 26 mmHg to
      15 mmHg (PaCO2 39.6 mmHg), and SpO2 declined from 98% to 92% (PaO2 69.2 mmHg).
      Nitrous oxide was discontinued immediately because pulmonary air embolism was
      suspected and the oxygen concentration was increased to 100%. At the same time
      the surgical procedure was discontinued. After 15 minutes, end-tidal PCO2
      recovered to 25 mmHg, and SpO2 recovered to 98% (PaO2 136.5 mmHg), and surgery
      was resumed. The patient recovered from anesthesia. The chest X-p at the end of
      operation, and pulmonary scintigraphy on the following day revealed no abnormal
      findings, but brain CT demonstrated a large quantity of air in both lateral
      ventricles.

PMID- 11345760
TI  - [Endotoxin adsorption and continuous hemodiafiltration in three septic patients].
AB  - We report 3 patients in septic shock with panperitonitis. Endotoxin adsorption by
      polymixin B affinity column (PMX) and continuous hemodiafiltration (CHDF) were
      performed immediately after the surgery. Septic shock was not improved in patient
      1 and 2 despite intensive care. Multimodal approach, including complete surgical
      repair, cardiovascular support and blood purification methods, is essential in
      treating septic patients.

PMID- 11345761
TI  - [Convulsion following the combination of single preoperative oral administration
      of enoxacine and single postoperative intravenous administration of flurbiprofen
      axetil].
AB  - We experienced a case of convulsion following the combination of single oral
      administration of enoxacine before an emergency operation and single
      postoperative intravenous administration of flurbiprofen axetil. The patient was
      an 87-year-old female referred to our hospital for severe abdominal pain. She was
      diagnosed as having the strangulation ileus, then underwent the emergent
      operation of partial resection of the necrotic small intestine under general
      anesthesia. Unfortunately we did not know that she had temporarily received oral
      enoxacine 200 mg, a new quinolone, administered by the previous doctor on the day
      before the operation. After the operation, flurbiprofen axetil 50 mg, a
      nonsteroidal anti-inflammatory drug, was given intravenously in thirty seconds
      due to postoperative pain. One minute after administration of the drug, she
      immediately developed a convulsive fit, severe disturbance of consciousness and
      apnea. We then administered at once, a single dose of diazepam intravenously for
      convulsion treatment, kept her airway open and controlled her ventilation.
      Convulsion disappeared in a minute and her condition improved gradually. We
      suspect that convulsive seizure may have been induced by the drug interaction
      between single oral dose of enoxacine before the operation and single intravenous
      dose of flurbiprofen axetil after the operation. We also suspect that the serum
      concentration of enoxacine was kept high because of metabolic disturbance and
      renal dysfunction resulting from her old age and dehydration. This case suggests
      that medication before the emergency operation must be considered in anesthetic
      management because of the possible side effect such as convulsion induced by the
      drug interaction between neuquinolones and anti-inflammatory drugs.

PMID- 11345762
TI  - [Early detection of hypoxia with BIS monitoring during percutaneous
      cardiopulmonary support].
AB  - We report a patient in whom hypoxia developed during percutaneous cardiopulmonary
      bypass (PCPS) and was detected with the lowering of the bispectral index (BIS)
      values. A 7-yr-old boy was managed with PCPS for the treatment of cardiogenic
      shock after cardiac surgery. His circulation was dependent on PCPS and pulse
      pressure was nearly zero. Signals by pulse oxymetry were undetectable and
      periodical blood gas analysis was performed to confirm proper oxygenation. BIS
      was monitored, and a gradual decrease in the value was observed. Careful
      observation also revealed darkening of the blood in the PCPS circuit and blood
      gas analysis showed severe hypoxia. Oxygen concentration of the gas to a PCPS
      oxygenator was increased immediately and new PCPS circuit was prepared. It took
      almost two minutes to exchange the circuit. Near circulatory arrest might have
      occurred during the procedure and BIS and suppression ratio (SR) became below 10
      and above 90, respectively. Both returned to the previous values 30 min after the
      replacement of the circuit. Severe hypoxia, otherwise overlooked, was detected
      with BIS monitoring and BIS reflected the circulatory status of the patient,
      especially of the brain. This monitoring is useful to confirm proper oxygenation
      during PCPS.

PMID- 11345763
TI  - [Usefulness of a simple expiratory gas monitor during sedation under spinal
      anesthesia].
AB  - We introduce a simple expiratory gas monitor during sedation under spinal
      anesthesia. A small extension tube for infusion used as a gas sampling line is
      placed in the nasal vestibule. It is necessary to make it sure that the point of
      the tube should not contact with the mucous membrane of the nose. Our method
      needs no special equipments such as Capnoxygen or Nazorcap, but a cheap extension
      tube available in any operating room. Therefore this is a simple method.
      Expiratory gas monitor can detect apnea early, airway obstruction and stenosis
      and predict PaCO2 during sedation. The change of fractional concentration of
      oxygen in inspired gas predicts the change of tidal volume. Increase in the
      former reflects a decrease in the latter under the administration of oxygen. It
      is possible to evaluate whether sedation became steady with analysis of
      respiratory pattern. However, nasal discharge may interrupt monitoring expiratory
      gas. Our simple method to monitor expiratory gas is useful during sedation under
      regional anesthesia.

PMID- 11345764
TI  - [Results of the investigation by questionnaires of power failure].

PMID- 11345765
TI  - [New studies on the history of anesthesiology--(7). What anesthetics were given
      to soldiers of the fifth regiment rescued from death march on Mount Hakkoda?].
AB  - Two hundred and ten soldiers belonging to the fifth regiment of the Japanese
      Imperial Army started their march on Mount Hakkoda in the early morning of
      January 23rd, 1902. In the afternoon, they unfortunately met with a bad weather
      of violent gale, heavy snowfall and biting coldness to lose their way to proceed
      to a small village Tashiro. In the following several days, many soldiers were
      frozen to death and only seventeen were rescued. They were brought to the Aomori
      Military Hospital for admission. Among them the First Lieutenant Kuraishi and two
      officers were almost free from frost bite but the Major Yamaguchi died next day
      and a soldier died two days after his admission without any surgical treatment.
      The remaining eleven underwent amputation of their frostbitten extremities under
      general anesthesia by open drop method with a mixture of chloroform and ether,
      because chloroform anesthesia per se was considered much more injurious than
      ether to patients with poor physical status. The Military Hospital announced that
      the Major Yamaguchi had died due to sudden cardiac arrest, but a lay view that he
      had committed suicide with his gun has widely prevailed, particularly since Jiro
      Nitta, a novelist, referred to it in his novel "Death March on Mount Hakkoda" in
      1971. According to newly discovered manuscripts written by a military surgeon Ki
      ichi Murakami who served in the rescue services, both hands of the Major
      Yamaguchi were heavily frostbitten and his fingers were strongly flexed unable to
      move the trigger of his gun. Considering situations including the dates of Sadae
      Nakahara's visit to Aomori who was a military surgeon of the Yamagata Military
      Hospital, the mysterious content of a telegram to Gentaro Kodama, the War
      Minister, from the General Shobun Tachimi, the 8th division commander and the
      sudden closure of the Hospital on February 2nd, when the Major Yamaguchi died,
      there is a possibility that high concentrations of chloroform vapour might have
      been compulsorily administered to the Major Yamaguchi to cause him cardiac
      arrest, which the executive members of the Japanese Imperial Army would have
      secretly expected.

PMID- 11345767
TI  - [A new protocol of dual energy acquisition on stress 201Tl and rest 99mTc
      tetrofosmin myocardial scintigraphy].
AB  - We carried out stress 201Tl (Tl) and rest 99mTc-tetrofosmin (TF) myocardial
      scintigraphy with dual energy acquisition in 24 patients with suspected ischemic
      heart disease performed coronary arteriography and elucidated the sensitivity of
      this method. One hour after light meal eating, TF (555 MBq) was injected
      intravenously at rest and after 3 minutes from injection of TF exercise or
      pharmacologic stress was performed. During stress Tl (111 MBq) was injected
      intravenously before end-point or at adequate point of pharmacologic stress. Dual
      energy acquisition using triple energy windows (TEW) was started after 5 minutes
      (early) and 4 hours (delayed) from stress. The sensitivity (Sn), specificity (Sp)
      and accuracy (Ac) in diagnosis of non-infarcted branches by using Tl (early)-TF
      (rest) and Tl (early)-Tl (delayed) were 79% vs. 53% (Sn), 78% vs. 96% (Sp) and
      79% vs. 71% (Ac) respectively. Accordance of uptake score of infarcted region
      between TF (rest) and Tl (delayed) was 70%. In conclusion, this protocol is
      seemed to be useful as usual protocol for detection of myocardial ischemia and
      viability during about only 1 hour.

PMID- 11345768
TI  - [Trial manufacture of a plunger to reduce finger exposure].
AB  - According to the results of to a survey conducted by the Japanese Society of
      Nuclear Medicine Technology in 1995, the mean monthly exposure dose to the trunk
      of nuclear medicine technicians was less than 0.2 mSv at more than 75% of the
      institutions, whereas the exposure dose to the fingers exceeded 0.5 mSv at 30% of
      the institutions. Many recent radiopharmaceuticals are being supplied as the
      syringe type, and while the syringe is surrounded by a tungsten or lead-glass
      shield, there is no shielding of the syringe needle or the plungers. The plastic
      plunger provides little shielding effect, and even when a tungsten plunger is
      used, calculating back from the leakage rate, the shielding effect for 99mTc is
      approximately 75%. We therefore trial-manufactured a plunger devised in such a
      manner as to considerably reduce exposure of the fingers and evaluated its
      shielding effect from leakage rate obtained with a dual-detector scintillation
      camera when the radionuclides 99mTc, 67Ga, 201Tl, and 123I were used. Its
      performance was satisfactory, with shielding effects (99mTc, 99%; 67Ga, 95%,
      201Tl, 95%; 123I, 73%) about the same or better than back-calculated from the
      leakage rates.

PMID- 11345769
TI  - [18F-FDG injections produced by a solid phase 18F-fluorination (FDG MicroLab):
      effects of 18F-FDG and the components on endotoxin and sterility tests].
AB  - Effects of 18F-FDG and components of the injections on endotoxin tests (Limulus
      tests) and sterility tests (Blood culture system) were determined with 18F-FDG
      injections produced by a solid phase 18F-fluorination (FDG MicroLab, GE). 18F-FDG
      injections with endotoxins shortened the time for gelling (turbidimetry),
      compared with that of the control (saline). Blood culture systems inoculated with
      18F-FDG injections and microorganisms showed positive results within 72 h of
      incubation for every species of microorganisms used in the present study
      (Bacillus subtilis, Candida albicans, Clostridium sporogenes, Micrococcus
      luteus). These results were quite similar to those for the control samples
      inoculated with saline and the microorganisms. Consequently, 18F-FDG and the
      components of the injections produced by the present methods may not
      significantly affect the endotoxin tests and sterility tests.

PMID- 11345770
TI  - [Method of evaluating the shielding effect of syringe shields and plungers].
AB  - The opportunities to use the syringe-type radiopharmaceuticals being supplied by
      manufacturers to conduct examinations in the ordinary clinical practice of
      nuclear medicine have recently increased, and the radiation doses to the fingers
      of those performing the examinations has been reduced. However, not much is known
      about the shielding effect of the syringe-type syringe shields and plungers. In
      order to evaluate their shielding effect, we devised a method in which leakage
      rates are calculated from the counts of the image data acquired with a 2-detector
      scintillation camera and compared with the values and graphs. The values made it
      possible to determine and compare single-direction leakage rates, whereas the
      graphs made it possible to determine and compare 360 degrees-direction leakage
      rates. This method is convenient, enables satisfactory result to be obtained in
      any institution, and appears to make it easy to understand the shielding effect.
      The validity of this method was confirmed in a comparative assessment with a
      survey-meter.

PMID- 11345771
TI  - [Prediction of effect of beta-blocker therapy in patients with dilated
      cardiomyopathy by using 123I-BMIPP, 123I-MIBG scintigraphy].
AB  - We investigated prediction of the efficacy of beta-blocker therapy in patients
      with dilated cardiomyopathy (DCM) by using myocardial scintigraphy with 123I
      BMIPP (BMIPP) and 123I-MIBG (MIBG). Thirty-seven patients with DCM were examined
      by myocardial scintigraphy with BMIPP and MIBG before beta-blocker therapy.
      Patients were classified into two groups, based on whether they improved > 10% of
      the left ventricular ejection fraction (LVEF) (improved group, n = 21) or not
      (unimproved group, n = 16). The extent and severity score of BMIPP for the
      improved group was significantly lower (p < 0.001) than that for unimproved
      group. It has been suggested that BMIPP is useful in evaluating the prediction of
      efficacy of beta-blocker therapy in patients with DCM.

PMID- 11345772
TI  - [Peripheral blood stem cell transplantation: current status and related issues].

PMID- 11345773
TI  - [Hematopoietic stem cells and stem cell biology].

PMID- 11345774
TI  - [Therapeutic strategy for leukemia: JALSG and the role of Japan in the 21st
      century].

PMID- 11345775
TI  - [Molecular mechanism of leukemogenesis].

PMID- 11345776
TI  - [A novel strategy for identifying the epitopes of autoantigens in autoimmune
      hemolytic anemia].

PMID- 11345777
TI  - [Antiphospholipid antibodies and thrombosis].

PMID- 11345778
TI  - [Autoimmunity and hemophagocytic syndrome].

PMID- 11345779
TI  - [Mechanisms of inhibitory signal transduction and autoimmunity].

PMID- 11345780
TI  - [Environmental factors and autoimmune diseases: immuno-dysregulation observed in
      silicosis patients].

PMID- 11345781
TI  - [High-dose therapy and peripheral blood stem cell transplantation for patients
      with aggressive non-Hodgkin's lymphoma remaining in initial remission: results of
      a feasibility study].
AB  - High-dose therapy with peripheral blood stem cell transplantation (HDT/PBSCT) was
      performed as one aspect of front-line therapy in patients with poor-risk
      aggressive non-Hodgkin's lymphoma (high-intermediate/high risk) according to the
      age-adjusted international prognostic index (aaIPI). Twenty-nine patients were
      enrolled in this study between November 1994 and March 1999. CHOP + etoposide
      (CHOP-E) was used as an initial chemotherapy and as a chemotherapy agent for the
      purpose of cell harvesting. Peripheral blood stem cells were harvested from 17
      patients, and HDT with CEC (carboplatin, etoposide, cyclophosphamide)/PBSCT was
      performed in 11 patients. Eighteen patients dropped out, including five for whom
      CHOP-E therapy was ineffective and 5 who did not give consent for cell harvesting
      or HDT/PBSCT. CHOP-E therapy produced complete remission (CR) in 15 out of 26
      patients (58%) after discounting the 3 who were ineligible among the 29 who were
      initially enrolled. The median observation period after PBSCT in the 11 patients
      who underwent HDT/PBSCT was 25 months (3 to 50 months), and the 3-year disease
      free survival rate was 73%. No serious complications associated with the
      transplantation were observed. We were able to confirm the feasibility and safety
      of HDT/PBSCT as one form of front-line therapy for aggressive non-Hodgkin's
      lymphoma in patients under 60 years of age.

PMID- 11345782
TI  - [Chronic myelogenous leukemia with marked thrombocytosis].
AB  - We report a case of chronic myelogenous leukemia (CML) with marked
      thrombocytosis. The patient was a 68-year-old woman who showed marked
      thrombocytosis (> 200 x 10(4)/microliter), a slightly increased leukocyte count
      without any immature myeloid cells in the peripheral blood, and no
      hepatosplenomegaly. Philadelphia chromosome (Ph) was detected by karyotype
      analysis and FISH. The bcr-abl transcript was detected by RT-PCR and the break
      point was located in the major bcr. Treatment with interferon-alpha was
      effective, reducing the proportion of Ph-positive cells from 56% to 7% within 21
      months. Detailed study of atypical cases of CML such as the present one may
      provide additional information about the disease pathogenesis.

PMID- 11345783
TI  - [Complete cytogenetic response obtained with unrelated donor lymphocyte infusion
      for relapse of chronic myeloid leukemia in blastic crisis after allogeneic bone
      marrow transplantation].
AB  - A 35-year-old man with chronic myeloid leukemia (CML) in blastic crisis (BC)
      received an allogeneic bone marrow transplant from an unrelated donor in October
      1998 after three cycles of chemotherapy. BC relapse developed on day 349 after
      transplantation. After one cycle of chemotherapy and treatment with interferon,
      the patient received donor lymphocyte infusion (DLI), and this resulted in a
      complete cytogenetic response 21 days later. Grade III acute graft-versus-host
      disease developed on day 25 after DLI, but this was resolved after administration
      of prednisolone. Disease relapse occurred at extramedullary sites on day 162
      after DLI, and the patient died of sepsis after receiving chemotherapy. This case
      illustrates that unrelated DLI can induce remission successfully in patients with
      relapse of CML in BC through a graft-versus-leukemia effect.

PMID- 11345784
TI  - [Disseminated atypical mycobacteriosis in a patient with chronic myelogenous
      leukemia].
AB  - A 61-year-old woman with a 6-year history of chronic myelogenous leukemia (CML)
      presented with recurrent fever in July 1996. Bone marrow aspiration, biopsy and
      chromosome analysis showed that CML was in the chronic phase. Bone marrow biopsy
      revealed nonspecific inflammatory lesions. Chest X-ray and computed tomography
      examinations demonstrated interstitial pneumonia. Cultures of gastric juice and
      bone marrow yielded colonies of Mycobacterium avium complex (MAC), and a
      diagnosis of disseminated atypical mycobacteriosis was made. Multidrug treatment
      including rifampicin, ethambutol, clarithromycin and ciprofloxacin was begun. The
      cultures subsequently became negative and the fever was resolved. However, fever
      eventually recurred and the patient died of multiple organ failure in October
      1997. since disseminated atypical mycobacteriosis complicating hematological
      disorders worsens the prognosis, its early diagnosis and prompt treatment are
      important. Although it is often difficult to identify atypical mycobacterium as a
      causal agent, frequent culturing of atypical mycobacterium from various sources
      including bone marrow fluid can be helpful for early diagnosis whenever fever of
      undetermined origin occurs in patients with hematological disorders.

PMID- 11345785
TI  - [Skin toxicity associated with bolus infusion of low-dose cytarabine].
AB  - A 4-year-old boy with ALL received low-dose ara-C (50 mg/m2/day, bolus). After 10
      fractions of ara-C, he developed an erythematous rash predominantly on the palms
      and soles, mimicking acral erythema except for the absence of pain. Chemotherapy
      was interrupted and the rash disappeared in four days. A similar rash occurred
      again just after the second cycle of ara-C had been started. Co-administration of
      dexamethasone improved the rash rapidly, thus allowing the chemotherapy to be
      continued, and suggesting the beneficial effect of corticosteroids. Although skin
      toxicity induced by low-dose ara-C is very rare and usually occurs after
      continuous infusion, it should also be borne in mind when considering bolus
      infusion.

PMID- 11345786
TI  - [Multiple myeloma complicated by bilateral abducens nerve palsy due to a tumor in
      the clivus].
AB  - A 62-year-old woman was admitted to our hospital because of double vision. Bone
      marrow aspiration revealed normal cellularity with 21.6% atypical plasma cells.
      Immunoelectrophoresis revealed a monoclonal component of IgG kappa in the
      patient's serum. Coronal and sagittal cranial MRI images showed a tumor in the
      clivus behind the sella turcica. The patient was diagnosed as having multiple
      myeloma complicated by double vision due to compression of the bilateral abducens
      nerve by a plasmacytoma. VAD therapy consisting of vincristine, doxorubicin and
      dexamethasone, followed by irradiation of the clivus tumor achieved only a
      transient therapeutic effect, and the double vision and bone disease worsened.
      Cranial nerve palsy may be a significant complication of multiple myeloma.

PMID- 11345789
TI  - Continuity of care: what does it really mean?

PMID- 11345788
TI  - Food and drug interaction education.

PMID- 11345787
TI  - Purchasing for profit.

PMID- 11345790
TI  - Dietitians in administrative roles.

PMID- 11345791
TI  - JCAHO update. Patient and family education and continuum of care.

PMID- 11345792
TI  - [Anemia and neoadjuvant hormone therapy in radical surgery of localized cancer of
      the prostate].
AB  - RATIONALE: Erythropoiesis is stimulated by androgens either through a direct
      action on bone marrow cells or through increased erythropoietin production.
      Androgen deprivation is a known cause for anaemia. The aim of this study was to
      evaluate the effect of neoadjuvant hormone therapy prior to radical surgery on
      haemoglobin (Hb) and haematocrit (Ht) levels in localised prostate cancer.
      MATERIAL AND METHOD: 47 patients with clinical localised prostate cancer were
      given LH-RH analogs plus flutamide for complete androgenic blockade (CAB) for at
      least 3 months prior to radical prostatectomy. A blood profile was obtained prior
      to start CAB and 3 months after therapy, and peri-operative transfusional
      requirements were evaluated. To assess any significant changes. Student's t test
      was used in the statistical analysis of paired data. RESULTS: In our study all
      patients (100%) showed decreased Hb and Ht levels after 3 months on CAB. Mean
      decline for Hb was 1.9 g/dL (range 1.6-2.2) p:0.0001, and for Ht 5.8% (range 4.8
      6.8) p:0.0001. Hb was lower than 12 g/dL in 10.6% patients after hormone therapy
      and anaemia results were normocytic-normochromic. 60% patients needed peri
      operative blood transfusion, 2 units of packed cells on average. CONCLUSIONS:
      Neoadjuvant CAB prior to radical prostatectomy results in a significant decline
      of Hb and Ht levels after 3 months treatment. Such decline may contribute to
      increase peri-operative transfusional requirements in a group of patients
      undergoing aggressive surgery which in itself involves a significant blood loss.

PMID- 11345793
TI  - [Differences in survival of patients with bladder cancer depending on depth of
      muscle infiltration].
AB  - OBJECTIVE: To study the survival of patients with bladder cancer and infiltration
      into the muscle who undergo radical cystectomy, documenting any survival
      difference based on the depth of muscle infiltration (pT2a vs. pT2b). MATERIAL
      AND METHOD: 109 patients with infiltration into the muscle (T2) in the TUR were
      treated with radical cystectomy between 1986 and 1996; 39 patients were excluded
      due to infra-staging and 2 died in the immediate postoperative: 68 patients were
      eligible for the study. Median follow-up was 51 months. At the time of analysis
      44 were alive (2 with tumoral disease and one with a second non-urological
      tumour), 21 had died (4 for causes other than vesical tumour) and 3 patients were
      considered lost to follow-up at 3, 31 and 111 months. Survival analysis was
      performed using the Kaplan-Meier method, and the variables were compared with the
      log-rank test. RESULTS: The 3- and 5-year overall survival of our series was 76%
      and 62%, while cancer specific survival was 80% and 70% respectively. Cancer
      specific survival at 5 years by stages was: pT0-83%, pT1-80%, pT2a-66% and pT2b
      60% (p = 0.52). The cystectomy specimen (pT0) showed no residual tumour in 15
      (22%) patients, and 5-year cancer specific survival in this group was 83% vs. 66%
      in patients with residual cancer (p = 0.24). CONCLUSIONS: Patients with pT2a and
      pT2b bladder cancer showed no differences in survival and we believe they should
      be all included in the same prognostic group (pT2). pT0 patients are a subgroup
      of patients with significant survival rates in which radical cystectomy should be
      considered as overtreatment, and a more conservative protocol should be
      preferred.

PMID- 11345794
TI  - [Can PSA density predict the response to alpha-blockers in benign prostatic
      hyperplasia?].
AB  - INTRODUCTION AND OBJECTIVES: In BPH there is a growth of both glandular and
      stromal components. Most of adrenoceptors sites are in the fibromuscular stroma.
      So the higher is the stromal/epithelial ratio, the more effective will alpha
      blockers be. There in an indirect way of stimating this ratio without performing
      a biopsy. Bearing in mind that PSA is produced by the prostatic epithelium, the
      lower PSA density (PSAd), the higher the stromal/epithelial ratio and the higher
      alpha-blocker activity. We pretend to study if PSAd is useful for predicting the
      response to alpha-blockers in BPH. MATERIAL AND METHODS: We studied 75 patients
      suffering from prostatism and diagnosed of bladder outlet obstruction secondary
      to BPH through IPSS symptom score, digital rectal examination, PSA, uroflowmetry,
      and transrectal ultrasound. All of them received Alfuzosin, 5 mg twice daily
      during 3 months, and then were evaluated again with IPSS and uroflowmetry.
      RESULTS: A statistically significant improvement was appreciated of the two
      studied parameters and in both groups of patient with regard to the pretreatment
      situation. A statistically significant better answer was also appreciated in the
      group of patient with smaller PSAd in comparison with the higher PSAd patients.
      CONCLUSIONS: Our results show that PDAd is usefu to estimate the
      stroma/epithelium ratio, and therefore the clinical response to alpha-blockers.

PMID- 11345795
TI  - [Post-surgical spindle cell nodule in kidney pelvis].
AB  - INTRODUCTION: The postoperative spindle cell nodule of the urinary tract is a
      being proliferative lesion similar to sarcoma in the microscopic exam. We present
      a case of modulein renal pelvis location. CASE: A woman presenting a stag horn
      lithiasis in left kidney was treated by LOC and percutaneous nephroscopy. Because
      of the large size of the stone a second intervention was required four weeks
      later. Then we discovered a 2 cm exophytic lesion in renal pelvis and removed it
      easily with a forceps. DISCUSSION: This kind lesion belong to the group of
      iatrogenic inflammatory pseudotumours, which are secondary to an injury that
      leads to a tissular repairing response. Differential diagnostic includes
      sarcomas. CONCLUSION: It is important that Urology and pathology specialist think
      of this tumour in patients having a recent surgical intervention. A mistake in
      the diagnosis would lead us to an unnecessary radical surgery.

PMID- 11345796
TI  - [Late pancreatic metastasis from renal carcinoma].
AB  - The appearance of solitary late metastases of renal cell carcinoma has seldom
      been documented. A male patient, who 5 years ago underwent left radical
      nefrectomy for renal cell carcinoma, presented with a solitary pancreatic
      metastasis (an uncommon site of metastasis for renal cell carcinoma), which was
      successfully treated with partial pancreatectomy. The diagnostic, treatment and
      prognostic implications of solitary late metastases are discussed.

PMID- 11345797
TI  - [Renal carcinoma with vena cava invasion. A new case].
AB  - It is well known that the renal carcinoma can progress to the renal vein and
      cava. The MRI is the most accurate study in order to assay the extension of the
      thrombus. The surgical management is based on the extension and location of the
      thrombus. New immunologic-based treatment is now being tested. We describe our
      experience with surgical management of the one case of renal carcinoma with cava
      vein thrombus. No evidence of progression is noted after 18 month follow up.

PMID- 11345798
TI  - [Giant renal hydatid cyst. Report of a new case].
AB  - In this paper, we present a case of huge renal hydatic cyst. We review the
      literature with regard the clinical presentation, diagnosis methods and surgical
      technique of treatment.

PMID- 11345799
TI  - [Metachronous contralateral Leydig cell tumor of the testis: conservative
      treatment].
AB  - Leydig cell tumors are the primary nongerm cell tumors of the testis, comprising
      approximately 1 to 3% of all testicular neoplasms. These tumors are bilateral in
      5 to 10% of cases. Hypoechoic testicular nodule associated to a child virilising
      syndrome or adult gynecomastia with negative testis tumor markers (AFP, B-HCG)
      show a high index suspicion for this entity. We report a case of metachronous
      contralateral Leydig cell tumor in a 32 years old man with a 9 year interval
      between presentations, in which we performed local excision of the lesion.
      Diagnostic an therapeutic aspects are reviewed in literature. Since preoperative
      diagnosis of Leydig cell tumors in difficult and clinical course unpredictible,
      radical orchiectomy has been the standard treatment. Emphasis is made on
      conservative management opportunity in patients with only one testis, small
      tumors (less than 2.5 cm) with biopsies from tumor bed negative and wishes to
      remain fertile and/or refuses androgen supplementation. Follow-up is mandatory by
      performing scrotal ultrasounds. CT scan, Chest X-Ray, tumor markers and hormone
      determinations (testosterone, estradiol, progesterone, LH and FSH).

PMID- 11345800
TI  - [Brucellar orchiepididymitis].
AB  - The brucellosis is an unusual entity whose incidence has diminished due to the
      improvement in preventive measures. We have carried out a retrospective study of
      all the patients admitted in our service between 1996 and 1998, with diagnosis of
      orchitis. Two of the 31 patients admitted for this reason presented a final
      diagnosis of brucellar orchiepididymitis. Both patients presented clinic of
      affectation from the general state accompanied by resistance to habitual
      antibiotic treatment. The patient's epidemic antecedents, accompanied by the
      suitable clinical evolution took to the suspicion of orchiepididymitis of
      brucellar etiology, with change in the antibiotic rule. The diagnosis of the
      process was obtained by means of serologic tests and blood cultures.

PMID- 11345801
TI  - [Embryonal rhabdomyosarcoma of the prostate. Report of a case and review of the
      literature].
AB  - The rhabdomyosarcoma (RMS) is a tumour derived from the mesenchymal cells that
      give origin to striate muscle. It appears most frequently at the pediatric age,
      although some appear in adolescence and in young adulthood. It is a high grade
      malignancy that metastatisis frequently (most importantly to the lung). There are
      two principal types: alveolar RMS and embrionary RMS. It can appear in any
      localization, being the most frequent the periorbitary area and the paranasal
      sinuses, and the second in frequency the genitourinary system (bladder, prostate
      and vagina). The therapeutic management is multidisciplinary and local therapies
      must always be accompanied with polychemotherapy. With combined treatments a
      curation rate of almost 90% can be reached in good prognosis cases, although it
      drops to 20% in those with disfavourable prognostic factors. The protocols with
      higher chemotherapy doses and subsequent rescue with blood-borne progenitor cells
      have not yet proved their efficiency. We present the case of a fifteen-year old
      patient with an embrionary rhabdomyosarcoma of the prostate, we analyze the
      clinical evolution and we revise the present therapeutic management of these
      neoplasies.

PMID- 11345802
TI  - [Kidney transplantation from living donor: a review from experience].

PMID- 11345803
TI  - [Who is responsible for PSA management and in which circumstances?].

PMID- 11345804
TI  - [Value of post-miction residue after urethrocervicopexy. Prospective study].
AB  - OBJECTIVE: To demonstrate that a high post-micturitional residue after a
      colposuspension is not a success predictive factor in the incontinence surgery.
      METHODS: We designed two identical groups of work, with the only difference of a
      high post-micturitional residue in one of them after the surgery (< 100 cc), and
      we evaluated the surgical results, with a follow-up of one year. We considered
      fails the presence of losses related with stress. RESULTS: There were no
      significative differences in the number of the deliveries, age, weight, length or
      body mass index in both groups. There were significative differences in the
      permanence of the urethral catheter and residue of urine, p < 0.001. There were
      no differences in the number of success in both groups. CONCLUSION: A high post
      micturitional residue after colposuspension is not an influent factor in the
      final result of surgery.

PMID- 11345805
TI  - [Urethrocervicopexy in aged women. Prospective study].
AB  - OBJECTIVES: [corrected] To demonstrate that Burch colposuspension gives a higher
      index of fails in over sixty years women affected of stress incontinence than in
      women under sixty years of age. METHODS: We established two groups of follow-up,
      each of them included twenty women affected of stress urine incontinence and
      surgical treatment indication. The only difference between both groups was the
      age of the patients, with a limit established in sixty years. We have evaluated
      the results of surgical intervention one year after it. The binomial parameters
      are compared with x2 test; the continuous parameters with the t-Student test for
      independent parameters. RESULTS: We did not find statistical significative
      differences with number of deliveries, body mass index, previous pelvic surgery,
      perineal rehabilitation, or the importance of the incontinence, between both
      groups of women. We found statistical significative difference in the novo
      micturition urgency or an increase in a previous urgency (p < 0.1) in women over
      sixty years. We did not find statistical significative differences in the number
      of successes and fails in both groups. CONCLUSION: The age is not a risk factor
      of failing of Burch colposuspension, but it is a risk factor of the appearance or
      increase of micturition urgency.

PMID- 11345806
TI  - [Camey II type orthotopic bladder replacement and its complications: 10-year
      experience].
AB  - BASIS: To evaluate the complications on patients undergoing radical cystectomy
      with Camey II ileal orthotopic neobladder. METHODS: To review our series of 61
      radical cystectomies performed between 1990 and 1999 for bladder cancer. The
      complications were divided in early (30 days or less) and late. RESULTS: A
      patient died at the immediate postoperative. It appeared 35 early complications
      on 30 patients: 8 related with neobladder (urinary fistula and urinary infection)
      and 27 not related, being the most frequent those appearing at bowel site, with
      10 early surgeries (16.4%). After evaluating 55 patients for late complications,
      39 presented some kind of complication: 38 related with neobladder and 13 not
      related, 30 patients underwent surgery, being 19 of them under endoscopic way.
      74.4% of continents by day and 31.4% at night. CONCLUSIONS: Despite the
      acceptable functional results, the orthotopic bladder substitution presents a not
      comptemtible rate of complications. In other way, a lack of standard criteria
      make difficult the comparation with other series and types of bladder
      substitution.

PMID- 11345807
TI  - Immunomodulating mechanisms in the lower respiratory tract: nitric oxide mediated
      interactions between alveolar macrophages, epithelial cells, and T-cells.
AB  - A number of immunomodulating mechanisms are necessary to prevent uncontrolled
      inflammation in the lower respiratory tract. Proliferative responses of immune
      cells are tightly controlled in both bronchi and alveoli in the healthy lung. In
      diseases such as bronchial asthma, there is not only a partial failure of these
      mechanisms, but also an immune-deviation with a propensity towards a Th2-cell
      involvement. The role of alveolar macrophages (AM) controlling T- and B-cell
      activation in the lower respiratory tract is discussed by considering mainly
      published results. This review focuses on immunomodulating mechanisms exerted via
      cytokines, such as Interleukin-10 (IL-10), transforming growth factor-beta (TGF
      beta), and Interleukin-1 receptor-antagonist (IL-1ra), prostaglandins, such as
      prostaglandin E2 (PGE2), and especially nitric oxide (NO). The Th1 and Th2
      concept in asthma is introduced, being the best-described mechanism of immune
      deviation in the lung. The possibility of re-inducing T-cell unresponsiveness is
      of particular interest. The physiological immunomodulating mechanisms used by AM
      are explained in detail, as they offer many possibilities for therapeutic
      immunomodulation. Special emphasis is put on the cGMP/phosphatase dependent,
      reversible mechanism of NO-mediated immunomodulation and differences in the
      activation of NO synthases between murine and human alveolar macrophages are
      mentioned.

PMID- 11345808
TI  - Late effects in long-term survivors of ALL in childhood: experiences from the
      SPOG late effects study.
AB  - With the use of more intensive regimens including prophylactic CNS treatment, the
      prognosis of children with ALL has dramatically improved over the last three
      decades. The aim of this cross-sectional, nationwide study was to comprehensively
      assess long-term toxicity in ALL survivors, with special attention given to
      neuropsychological morbidity, and to look for possible differences in cognitive
      outcome between children having received prophylactic cranial irradiation and
      those not having received it. Between 1994 and 1996, long-term survivors of ALL
      were assessed in a multi-center setting according to a standardized protocol
      which included, besides usual clinical and laboratory investigations, a
      comprehensive endocrine work-up. Additionally, children having received
      anthracyclines were checked for possible late cardio-toxicity with
      echocardiography and ECG. Intellectual performance was evaluated with
      standardized neuropsychological tests (age-adapted versions of the Wechsler
      test). One-hundred and fifty patients were eligible for the study. The median age
      at diagnosis was 5 years and at evaluation 16 years, for a median follow-up of 10
      years. Thirty-five patients had cranial irradiation as part of the prophylactic
      CNS treatment. One-hundred and forty (93%) of the 150 eligible patients were
      completely evaluated in terms of global long-term toxicity: 117 (83%) long-term
      survivors had no (n = 61) or only minimal (n = 56) late toxicity; 19 (14%)
      suffered from moderate impairments; 4 (3%) showed severe somatic or
      neuropsychological sequelae. Intellectual performance could be assessed in 147
      (98%) of the 150 eligible patients. The mean global, verbal and non-verbal IQs
      (103, 105 and 101 respectively) of the ALL survivors as a group were comparable
      with those found in the general population. The results of the comparison between
      children having and those not having received prophylactic cranial irradiation
      showed: 1) significantly higher scores in chemotherapy-only treated patients,
      both for the global and the verbal performances; 2) significantly poorer results
      in specific items of the Wechsler test (short-term verbal memory, arithmetics,
      concentration/speed of processing) in irradiated children. These findings which
      show the deleterious role of cranial irradiation correlate well with many other
      reports found in the literature. However, they could have been influenced by the
      significantly longer time interval observed between therapy and evaluation in our
      irradiated patients. Prospective studies are needed to further characterize the
      potential neuropsychological hazards of chemotherapy and their evolution over
      time.

PMID- 11345809
TI  - Community-acquired pneumonia--which patients are hospitalised?
AB  - BACKGROUND AND OBJECTIVE: Patients with community-acquired pneumonia can be
      allocated into low and high-risk mortality groups by simple clinical criteria. We
      studied the value of the stratification for outcome as proposed by Fine, et al.
      to guide the decision for in-hospital versus outpatient treatment in the
      emergency department. PATIENTS AND METHODS: We studied demographic data, risk
      group stratification and decision-making for in-hospital versus outpatient
      treatment in 101 consecutive medical emergency department patients with community
      acquired pneumonia. We also analysed predictive factors for hospitalisation of
      low-risk patients. We obtained complete 30 day follow-up information. RESULTS:
      Forty-three of 44 high-risk patients were hospitalised after medical emergency
      department triage. Twenty-seven (47%) of 57 low-risk patients were hospitalised
      as well. Based on routine clinical assessment, hospitalisation of low-risk
      patients was required for poor medical condition or severe pneumonia (67%), for
      lack of social support (15%) and for relevant comorbidity (18%). In an univariate
      analysis, age (p = 0.003), C-reactive protein (p = 0.0006), presence of
      comorbidity (p = 0.0001), Charlson index (p = 0.0001) and active oral steroid
      treatment (p = 0.028) were significantly correlated with hospitalisation of low
      risk patients. The 30-day mortality rate was 32% in patients allocated to the
      high-risk group at the time of diagnosis in the emergency department, compared to
      0% in low-risk patients. CONCLUSION: Simple clinical criteria distinguish well
      between low and high 30-day-mortality risk in patients diagnosed with community
      acquired pneumonia. Nevertheless, 47% of low-risk patients require in-hospital
      treatment. Age, C-reactive protein, presence of comorbidity and steroid treatment
      are significantly correlated with hospitalisation of low-risk patients with
      community-acquired pneumonia.

PMID- 11345810
TI  - Renal safety of combined cyclooxygenase 2 (COX-2) inhibitor and angiotensin II
      receptor blocker administration in mild volume depletion.
AB  - PRINCIPLES: Drugs that either inhibit prostaglandin synthesis or antagonise
      angiotensin II effects are likely to impair renal function, especially in
      patients with an activated renin-angiotensin-aldosterone system. Of the former,
      nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used, and newer agents
      with cyclooxygenase 2 (COX-2) specific inhibition may have fewer renal side
      effects compared to non-selective NSAIDs. We therefore investigated whether
      combination of a COX-2 inhibitor with an angiotensin II subtype 1 (AT1) receptor
      blocker is safe with regard to preservation of normal renal function in a state
      of slight volume contraction. METHODS: Mild volume depletion was induced by a
      salt-restricted diet in 5 healthy volunteers who were then given a single dose of
      400 mg celecoxib, a COX-2 inhibitor, alone or in combination with 150 mg
      irbesartan, an AT1 receptor blocker. Glomerular filtration rate (GFR) and
      effective renal plasma flow (ERPF) were determined by measuring inulin and PAH
      clearance respectively, along with plasma renin activity (PRA) and urinary
      electrolyte excretion before and over 100 minutes after drug administration.
      RESULTS: PRA was high prior to drug administration, indicating slight salt
      depletion, and dropped by 65% after intake of celecoxib alone (p = 0.008) but
      only by 25% after combined intake with irbesartan (p = n.s.). GFR was not
      affected either by celecoxib alone or by combined administration with irbesartan.
      In contrast, ERPF increased by 28% 80 minutes after simultaneous drug intake (p =
      0.029), but not after celecoxib alone. Renal sodium and potassium excretion did
      not significantly change under celecoxib alone or in combination with irbesartan.
      CONCLUSION: Selective COX-2 inhibition by celecoxib in combination with an AT1
      receptor blocker (irbesartan) has no acute adverse effects on renal haemodynamics
      and renal salt handling in slightly volume-depleted subjects with normal renal
      function. Moreover, our data obtained in humans appear to confirm the co
      regulatory interaction of COX-2 and angiotensin II in the control of renin
      release, as suggested by animal studies.

PMID- 11345813
TI  - [The "day-care center disease": a new acquired immunodeficiency caused by
      cytomegalovirus infection epidemics?].

PMID- 11345811
TI  - Contact dermatitis after temporary henna tattoos--an increasing phenomenon.
AB  - Four patients developed contact dermatitis to black henna tattoos on holiday in
      the Middle East and Asia. Two to ten days after skin painting an itchy, reddish
      swelling developed at the site of the tattoo exactly following its sharply
      demarcated borders. Histological investigation of the lesions revealed spongiotic
      dermatitis with dense lymphohistiocytic infiltrates. Patch testing in all
      patients showed a strong reaction to p-phenylenediamine (PPD). The other tests,
      including standard series and henna powder, were all negative. Healing time after
      application of topical class III and IV steroids was prolonged. These reports
      show an impressive side effect of temporary tattoos with possible long-term
      damage. Rather than henna, the causative agent in the pastes used for temporary
      tattoos appears to be PPD, a widely used dye that is added to the pastes in high
      concentrations to produce a darker shade. The growing incidence of this
      complication requires close observation, while practitioners should be aware of
      this sensitisation and of possible subsequent allergic reactions, especially
      after hair colouring with dyes based on PPD.

PMID- 11345814
TI  - [Acute respiratory distress syndrome in children].
AB  - The acute respiratory distress syndrome (ARDS) encountered in a child may be
      either due to a primary lung infection or may be secondary to a systemic
      inflammatory response of varying origin. Therapy is based on: 1) the mechanical
      ventilation strategy aimed at maintaining the functional residual capacity by
      alveolar recruitment using positive end expiratory pressure and to limit
      secondary pulmonary lesions by using small tidal volumes, 2) prone positioning as
      soon as sufficient stability is achieved; 3) optimizing tissue oxygen delivery by
      cardiac support; 4) correction of any other organ dysfunction. If this
      conventional approach is not sufficient experimental therapies may be tempted
      given the vital risk. For instance inhaled nitric oxide and high frequency
      oscillation ventilation may be a valuable support. Newer techniques, such as
      partial liquid ventilation, are being developed and could become useful
      therapeutic options. After the acute phase a close medical follow-up is
      mandatory. Because of the possibility of a chronic respiratory insufficiency with
      negative consequences on the right ventricular function, these patients may need
      long term oxygen therapy and diuretics. Cardiac echography helps orientation in
      maintaining or discontinuing this long term therapy by estimating the arterial
      pulmonary pressure.

PMID- 11345816
TI  - [Polyuria, pollakiuria, and nocturia in children: diagnostic and therapeutic
      approach].
AB  - Polyuria is defined as the passage of large volumes of diluted urine secondary to
      an abnormality of urine concentration. This disorder can result either from
      deficient secretion of vasopressin (cranial diabetes insipidus), or from renal
      resistance to vasopressin (nephrogenic diabetes insipidus), primary polydipsia,
      osmotic diuresis, electrolytic disorders or drugs. Suspicion of impaired renal
      concentration ability can be confirmed by a fluid deprivation test. The
      administration of exogenous vasopressin allows to clarify the pathogenetic
      mechanism. Once the mechanism responsible for polyuria has been clarified it is
      mandatory to search for underlying causes. Treatment of polyuria should be
      causal, if its origin is known, and/or symptomatic in order to prevent severe
      dehydration. Symptomatic treatment of cranial diabetes insipidus consists of
      administering exogenous vasopressin. Salt restriction associated to a combined
      administration of hydrochlorothiazide/amiloride or
      hydrochlorothiazide/indomethacin can reduce urine output by 20 to 50% in case of
      nephrogenic diabetes insipidus. Pollakiuria is defined as a daytime urinary
      frequency. It can be isolated or may be a manifestation of lower urinary tract
      infections, bladder instability, nephrolithiasis or concentrated acidic urines.
      Detailed history and physical examination represent major clues to diagnostic.
      Therapy of pollakiuria can be causal or symptomatic using anticholinergic drugs
      or reeducation in case of bladder instability. Nocturia is characterized by
      voluntary nocturnal micturitions secondary to conditions inducing impaired renal
      concentration ability, or to heart failure.

PMID- 11345815
TI  - [Meningococcemia: epidemiology, clinical features, physiopathology, primary
      management, and future treatments].

PMID- 11345817
TI  - [Hyperaminoaciduria in children].
AB  - Hyperaminoaciduria is a major disorder to be considered in the event of growth
      and mental retardation, convulsion and other unexplained clinical symptoms. This
      review should enable the general practitioner to determine the conditions
      necessitating urinary and blood amino acid analyses in order to improve the
      treatment of children presenting rare pathologies, the prognosis of whom depends
      on the rapidity of the intervention. The diagnosis and treatment of hereditary
      and renal hyperaminoaciduria are discussed and a physiological and
      physiopathological synthesis of the tubular reabsorption of amino acids is
      presented. The different clinical entities associated with hyperaminoaciduria are
      then briefly described according to their origin (renal or prerenal).

PMID- 11345819
TI  - [Update on the diagnosis and treatment of supraventricular tachycardia in
      children].
AB  - Multiple advances in the understanding of arrhythmia mechanisms as well as the
      advent of new drugs and the radiofrequency catheter ablation have revolutionized
      the antiarrhythmic management in children. With the availability of these
      therapeutic options an improved knowledge of the treatment options, their
      indications and risks is required. Despite these improvements, supraventricular
      tachycardias remain an important and challenging problem, because of steadily
      growing numbers of children and adults presenting with complex supraventricular
      arrhythmias years after cardio-thoracic interventions.

PMID- 11345820
TI  - [Non-surgical approach in congenital cardiopathy].
AB  - The treatment of congenital or acquired heart defects by transcatheter therapy
      has crossed a period of rapid expansion in the last 10 years and is now an
      important adjunct to surgery. Balloon valvuloplasty can be considered as the
      treatment of choice for pulmonic and aortic congenital valvar stenosis as well as
      closure of a patent ductus arteriosus. The short hospital stay and absence of a
      scar make this approach very attractive. With the introduction of new techniques
      and devices, transcatheter therapy has become common for a number of other
      anomalies such as the atrial septal defect and soon some ventricular septal
      defects. It is necessary to maintain careful indications and compare the results
      with conventional surgery in order to assess the risks and benefits of these new
      techniques.

PMID- 11345821
TI  - [Quiz on radiology].

PMID- 11345822
TI  - [Accident prevention in early childhood].
AB  - Accidents are the first cause of mortality and morbidity in children and
      adolescents of both sexes as from their first month of life. Also they are the
      first cause of hospitalization and thus have an important economical impact. The
      knowledge of the mechanisms of injury can neither be transposed from a place to
      another nor be extrapolated with time. For this reason we developed in 1989 a
      prospective data base for injuries of children and adolescents from 0 to 16 years
      of age occurring in our state (canton de Vaud, Switzerland). From Jan 1st, 1990
      to Dec 31st, 1999, we recorded more than 28,000 cases. Infants and young children
      are involved in domestic injuries, accidents on playgrounds and in traffic
      accidents being pedestrians or passengers. We analyze the circumstances of
      accidents and point out their prevention programs and their efficiency. We try to
      demonstrate why children injuries are not fatalities but depend on mechanisms
      which can be predicted inarticular by an adequate information.

PMID- 11345823
TI  - [Prematurity, representations, and parental trauma].

PMID- 11345824
TI  - [Prevention of risky behaviors in adolescence].
AB  - A workshop of the French speaking meeting of practical paediatrics was dedicated
      to the prevention of risk behaviour among adolescents. Concrete and every day
      issues were discussed through risk taking during the transitional stages of
      adolescence. Parents and adolescence demand and health needs were debated, such
      as the absence of demand and expressed needs from the adolescent him/herself.
      Evaluation of the at risk situation was clarified.

PMID- 11345825
TI  - Medicaid and Medicare reimbursement for flow cytometry.
AB  - Medicaid, a program administered by individual states but involving federal
      funding, is the source of medical coverage for many low-income patients. This
      method of reimbursement is crucial for many flow cytometry laboratories, but is
      not well understood by many laboratory professionals. Conversely, flow cytometry
      often is not well understood by administrators in Medicaid offices. The potential
      exists for great variation in Medicaid reimbursement for flow cytometry services
      from state to state. As a first step toward elucidating the extent of this
      variation and bringing more information about Medicaid to laboratory
      professionals, state Medicaid offices were asked to provide the fee-for-service
      reimbursement for flow cytometry services. These services included Current
      Procedural Terminology (CPT) codes 85045 (reticulocyte counts), 86359 (total T
      cell count), 86360 (absolute CD4 and CD8 counts, with ratio), 86361 (absolute CD4
      count), 86812 (HLA typing, single antigen [B27]), 88180 (immunophenotyping, per
      surface marker), and 88182 (DNA, cell cycle analysis). Data were collected on
      technical and professional components and on global reimbursement. Wide variation
      exists in reimbursement amounts for these tests. Variation for CPT code 88180 was
      markedly pronounced.

PMID- 11345826
TI  - Manual differential cell counts help predict bacterial infection. A multivariate
      analysis.
AB  - We developed logistic regression models that combine information from the
      automated CBC and manual 100-cell differential counts to predict bacterial
      infection. The logistic models were fitted from a case group of 116 patients with
      proven bacterial infection and a control group of 930 presumably uninfected
      outpatients. A 4-variable, 15-parameter model, which includes automated absolute
      neutrophil, manual band, and manual immature granulocyte counts, performed best
      with a receiver operating characteristic (ROC) curve area of 89%. A more
      practical 2-variable model including automated absolute neutrophil and manual
      band counts performed almost as well with an ROC curve area of 86%. The automated
      neutrophil count-only model is less informative with an ROC curve area of 78%.
      The combined information from automated and manual differential cell counts more
      accurately predicts bacterial infection than automated counting alone. Despite
      these modest improvements, the high cost of manual differential cell counts
      dictates careful patient selection. The supplemental information gained from
      manual differential counts is most useful for patients with low to normal
      neutrophil counts (8,000/microL [8.0 x 10(9)/L] or less). Further studies are
      indicated to determine the characteristic patient populations deriving maximal
      benefit from this information.

PMID- 11345827
TI  - Comparison of lymphoid neoplasm classification. A blinded study between a
      community and an academic setting.
AB  - The revised European-American classification of lymphoid neoplasms has been
      reported as reproducible among expert pathologists and feasible in a community
      setting. We evaluated the reproducibility of lymphoid neoplasm diagnoses between
      a community and an academic center. We subtyped 188 lymphoid neoplasms using
      revised European-American classification criteria. Clinical findings, histologic
      or cytologic preparations, paraffin-section immunostains, and flow cytometry data
      were reviewed as appropriate. Diagnoses were compared only after completion of
      the study. Lymphoma subtype was concordant for 167 (88.8%) of 188 cases.
      Discordant cases included 15 B-cell, 2 T-cell, and 4 Hodgkin lymphomas. For B
      cell neoplasms, discordance was most often due to classifying diffuse large cell
      lymphoma as another aggressive subtype of lymphoma (n = 6), marginal zone
      lymphoma as another subtype (n = 4), or follicle center lymphoma grade II as
      grade III (n = 3). For Hodgkin disease, discordance was most often due to
      classifying nodular sclerosis as mixed cellularity type (n = 3). Comparison of
      community and academic center diagnoses demonstrated high concordance for most
      revised European-American classification subtypes. Some sources of discordance
      have been addressed in the new World Health Organization classification of
      neoplastic diseases of the hematopoietic and lymphoid tissues.

PMID- 11345828
TI  - Diagnostic value of tests for reticulated platelets, plasma glycocalicin, and
      thrombopoietin levels for discriminating between hyperdestructive and hypoplastic
      thrombocytopenia.
AB  - We measured reticulated platelets (RPs) and plasma glycocalicin (GC) and
      thrombopoietin (TPO) levels simultaneously in 107 thrombocytopenic patients to
      clarify the diagnostic value of these tests for discriminating hyperdestructive
      from hypoplastic thrombocytopenia. The percentage of RPs and GC index (plasma GC
      level normalized for the individual platelet count) were markedly elevated in
      patients with idiopathic thrombocytopenic purpura (ITP) but normal or slightly
      elevated in patients with aplastic anemia (AA) or chemotherapy-induced
      thrombocytopenia (ChemoT). For RP percentage for diagnosing hyperdestructive
      thrombocytopenia the sensitivity and specificity were excellent but were lower
      for the GC index. Absolute RP counts and plasma GC levels were markedly decreased
      and plasma TPO levels markedly elevated in patients with AA or ChemoT, but
      absolute RP counts and plasma GC levels were moderately decreased and plasma TPO
      levels only slightly elevated in patients with ITP. The sensitivity and
      specificity of plasma TPO levels for diagnosing hypoplastic thrombocytopenia were
      excellent. Using the RP percentage and plasma TPO levels in combination improved
      specificities. Simultaneous measurement of RP percentage and plasma TPO level may
      help discriminate thrombocytopenia of unknown cause in routine hematologic
      practice.

PMID- 11345829
TI  - Universal leukoreduction of cellular blood components in 2001? Yes.

PMID- 11345830
TI  - Universal leukoreduction of cellular blood components in 2001? No.

PMID- 11345831
TI  - Clinical perception of disease probability associated with Bethesda System
      diagnoses.
AB  - The degree to which clinical perceptions of Papanicolaou smear sensitivity
      contribute to patient mismanagement is uncertain. A voluntary, anonymous
      questionnaire was mailed to 350 obstetricians/gynecologists (OGYNs) and 350 other
      primary care providers (PCPs) located in Pennsylvania or Ohio. The clinicians
      estimated the probability of no disease, dysplasia, and invasive carcinoma for 1
      of 7 Bethesda System diagnoses. Differences in probability estimates between
      provider types and between the clinicians and medical literature data were
      measured. The response rate was 22.7%. Compared with published values, clinicians
      estimated similar disease probabilities for many diagnoses. However, for some
      diagnoses, the probability estimates differed considerably from published values
      (e.g., overestimation of dysplasia and invasive carcinoma for benign diagnoses
      and underestimation of dysplasia for some dysplasia diagnoses), and such errors
      could contribute to patient mismanagement. OGYNs generally were more accurate in
      probability estimates than PCPs. Methods to convey more accurately these
      diagnostic disease probabilities should be examined.

PMID- 11345832
TI  - Immunoreactivity for hepatocyte paraffin 1 antibody in hepatoid adenocarcinomas
      of the gastrointestinal tract.
AB  - Hepatocyte paraffin 1 (Hep Par 1) is a monoclonal antibody considered almost
      specific for normal and neoplastic hepatocytes, that can be used on formalin
      fixed paraffin-embedded tissues. Hep Par 1 reactivity has been demonstrated
      consistently in hepatocellular carcinomas and hepatoblastomas but only rarely in
      cholangiocarcinomas and metastatic tumors to the liver. Although its role as a
      marker of hepatocytic differentiation in primary liver tumors has been studied
      extensively, Hep Par 1 expression has not been explored in extrahepatic lesions,
      especially rare adenocarcinomas with hepatoid morphologic features. We studied 7
      hepatoid adenocarcinomas of the gastrointestinal tract (6 gastric and 1 from the
      gallbladder) for Hep Par 1 immunoreactivity. Focal Hep Par 1 expression was seen
      in 6 of 7 tumors. These hepatoid adenocarcinomas also showed reactivity for alpha
      fetoprotein and carcinoembryonic antigen. The presence of Hep Par 1 reactivity in
      extrahepatic hepatoid adenocarcinomas underscores the fact that Hep Par 1
      expression is not unique to primary hepatocellular neoplasms. Adenocarcinomas
      with hepatoid features must be considered in the differential diagnosis of Hep
      Par 1-positive lesions.

PMID- 11345833
TI  - Cytokeratins 7, 17, and 20 reactivity in pancreatic and ampulla of vater
      adenocarcinomas. Percentage of positivity and distribution is affected by the cut
      point threshold.
AB  - We studied reactivity of cytokeratins (CK) 7, 17, and 20 in 64 pancreaticobiliary
      adenocarcinomas to examine the effect of different cut-point thresholds on
      "positive" results, compare ampulla of Vater and pancreas adenocarcinomas, and
      provide additional experience with CK17 reactivity. Almost all neoplasms had
      extensive CK7 reactivity. The number of CK20-positive cases decreased from 29
      (45%; any stained cells) to 19 (30%; > 25% staining) to 14 (22%; > 50% staining)
      with an increasing threshold of reactive cells. Similar shifts in the
      distribution of CK7 and CK20 reactivity occurred when different thresholds of
      reactivity were used for a positive result. There were no differences in CK7 or
      CK20 reactivity in pancreas only, ampulla only, and neoplasms involving both
      sites. Of 64 adenocarcinomas, 29 (45%) had no or single-cell CK17 reactivity, and
      19 (30%) had reactivity in more than 50% of neoplastic cells. Ampulla of Vater
      and pancreas adenocarcinomas have similar CK immunophenotypes that cannot assist
      in distinguishing ampullary from pancreatic neoplasms on endoscopically procured
      tissue. CK17 staining occurs in approximately 50% of pancreaticobiliary
      adenocarcinomas and is usually patchy. Single antibody staining results,
      especially CK7 and CK20 coordinate reactivity, are influenced by the reactivity
      threshold used.

PMID- 11345834
TI  - A comparison of routine and rapid microwave tissue processing in a surgical
      pathology laboratory. Quality of histologic sections and advantages of microwave
      processing.
AB  - Rapid processing of histopathologic material is becoming increasingly desirable
      to fulfill the needs of clinicians treating acutely ill patients. Traditional
      techniques for rapid processing of paraffin-embedded tissues require 4 to 5
      hours, delaying treatment for some critically ill patients and requiring
      additional shifts of technologists in the laboratory. Microwave processing
      further shortens this time, allowing even more rapid histopathologic diagnosis.
      Few data exist comparing quality of microwave-processed tissue with that
      processed by more traditional techniques. We randomly selected 158 paired
      specimens from 111 patients. One member of the pair was processed routinely
      overnight, while the other was processed by the rapid microwave technique. The
      slides then were compared for quality of histologic preparation in a blinded
      fashion by 2 pathologists. Eight routinely processed specimens were judged as
      suboptimal, while 6 microwave-processed specimens were judged as suboptimal and 1
      was considered unsatisfactory for evaluation. In the remaining cases, the
      material obtained by the 2 techniques was considered of identical quality.
      Microwave processing considerably shortens the preparation time for permanent
      histologic sections without a demonstrable decrease in section quality or
      "readability."

PMID- 11345835
TI  - Biologic markers in ductal carcinoma in situ and concurrent infiltrating
      carcinoma. A comparison of eight contemporary grading systems.
AB  - The relevance of 8 contemporary classification and grading systems for ductal
      carcinoma in situ (DCIS) of the breast was examined in 100 tumors by comparing
      DCIS grade with grade of the concurrent infiltrating ductal carcinoma (IDC).
      Besides tumor size and nodal status, the immunohistochemical parameters in both
      lesions were compared, including estrogen receptor, progesterone receptor, c-erbB
      2 protein, E-cadherin, vimentin, Ki-67 (MIB1), and p27. Nuclear grading of DCIS
      alone or in combination with architectural pattern and necrosis showed the best
      correlation with grade of the invasive component. There also was a positive
      correlation between every biologic marker expressed in DCIS and in the concurrent
      IDC, supporting a clonal relationship. Biologic markers varied between the
      different grades of DCIS. DCIS is heterogeneous, and the progression of DCIS to
      IDC may be from low-grade DCIS to low-grade IDC and high-grade DCIS to high-grade
      IDC. This concept is different from the conventional model held for
      intraepithelial neoplasia in the cervix, vulva, vagina, and skin, in which there
      is increasing severity of in situ atypia (dysplasia) before the development of
      stromal invasion.

PMID- 11345836
TI  - Elevated expression of caveolin-1 in adenocarcinoma of the colon.
AB  - Caveolins 1, 2, and 3 are the principal proteins of caveolae, the vesicular
      invaginations of the plasma membrane. Several reports have suggested that
      caveolin-1 may have a role in cellular transformation and tumorigenesis. We
      studied the expression of caveolin-1 and caveolin-2 in normal epithelium,
      adenoma, and adenocarcinoma of the colon and their possible role in
      tumorigenesis. Formalin-fixed, paraffin-embedded sections of 41 cases of
      adenocarcinoma and 13 cases of adenoma of the colon were stained
      immunohistochemically with anti-caveolin-1 and anti-caveolin-2 antibodies. The
      expression of caveolin-1 was elevated in the overwhelming majority of the
      adenocarcinomas, while most normal colonic epithelium and adenomas showed little
      or no staining. There was significant statistical correlation of the expression
      of caveolin-1 with adenocarcinoma but not with tumor stage. Expression of
      caveolin-2 was undetectable in all of the normal colonic glands, adenomas, and
      carcinomas. We discuss the possible clinical implications of our findings within
      the context of caveolins and signal transduction.

PMID- 11345837
TI  - Expression of decorin, transforming growth factor-beta 1, tissue inhibitor
      metalloproteinase 1 and 2, and type IV collagenases in chronic hepatitis.
AB  - Decorin is a small extracellular matrix proteoglycan. It binds and modulates
      transforming growth factor (TGF)-beta 1 action, the major stimulator of
      fibrogenesis. Its role in the pathogenesis of human liver cirrhosis is unknown.
      Therefore, we studied the relationship of the 2 proteins in normal human liver
      and in 43 chronic hepatitis and liver cirrhosis specimens. To understand the
      mechanism that maintains matrix deposition in stage IV hepatitis, we studied
      expression of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2, as well
      as the activities of type IV collagenases. Gene expression was analyzed on
      messenger RNA and protein level by morphologic and biochemical approaches.
      Decorin proved to be an early marker of fibrogenesis, and its deposition
      increased parallel to that of TGF-beta 1 and to inflammatory activity. Liver
      fibrosis progressed despite high temporospatial expression of decorin with TGF
      beta 1. Neither decorin nor TGF-beta 1 protein deposition increased further in
      cirrhosis with low inflammatory activity, suggesting that impaired extracellular
      matrix catabolism rather than active production plays a role in this stage. This
      possibility was supported by high message levels of metalloproteinase inhibitors,
      no 72-kd collagenase activities, and low 92-kd collagenase activities.

PMID- 11345838
TI  - Histopathology of fibroadenoma of the breast.
AB  - The aim of this study was to make a thorough inventory of the histologic features
      of epithelium and stroma within and adjacent to breast fibroadenomas in 396
      cases. Breast fibroadenomas seemed to display a wide spectrum of proliferative
      and nonproliferative histologic changes. Hyperplasia (excluding mild hyperplasia)
      within the fibroadenoma was found in 32.3% of cases. Carcinoma in situ (CIS; 5
      ductal, 3 lobular) was found in 8 fibroadenomas (2.0%) removed from 6 patients,
      the youngest of whom was 40 years of age. In 3 cases CIS was not confined to the
      fibroadenoma, but also involved the adjacent parenchyma. No invasive carcinoma
      was present within this series. Complex histologic features were seen in 40.4% of
      cases, mostly in relatively older patients (mean age, 35.4 years). Hyperplasia in
      adjacent tissue was found in 8.8% of cases, usually in older patients (mean age,
      45.5 years). Known risk-elevating lesions in and around breast fibroadenomas
      occur frequently and mostly in patients older than 35 years. These findings may
      have consequences for the clinical management of a subgroup of patients with
      fibroadenoma.

PMID- 11345839
TI  - Lack of relevant information for tumor staging in pathology reports of primary
      cutaneous melanoma.
AB  - For the T classification of primary cutaneous melanoma, the current American
      Joint Committee on Cancer staging (AJCC) system relies on tumor thickness and
      level of invasion. A new T classification has been proposed based on thickness
      and ulceration. The slides and reports of 135 departmental pathology
      consultations of patients referred to a major cancer center with a diagnosis of
      primary cutaneous invasive malignant melanoma were examined. Whether the outside
      pathology reports contained information on tumor thickness, level of invasion,
      and ulceration was recorded. Dermatopathologists had issued 76.3% of the reports
      and general surgical pathologists, 24.3%. Information provided was as follows:
      tumor thickness, 97.8%; Clark level, 71.9%; and presence or absence of
      ulceration, 28.1%. Of the 97 melanomas with no comment on ulceration, 17 were
      indeed ulcerated. Thus, the lack of a comment on ulceration cannot be equated
      with the absence of ulceration. The present study documents that many pathology
      reports on melanomas lack sufficient information for AJCC staging. Therefore,
      review of outside pathology material is necessary not only to confirm or revise
      the tumor diagnosis but also to provide clinicians with histologic parameters
      required for AJCC staging.

PMID- 11345840
TI  - Coexpression of cytokeratins typical for columnar and squamous differentiation in
      sinonasal inverted papillomas.
AB  - Cytokeratin (CK) expression was studied in 22 sinonasal inverted papillomas.
      Columnar (respiratory) epithelium in inverted papillomas abundantly expressed
      CK7, CK8, CK18, and CK19. Immunoreactivity for CK5/14 and CK17 was found in basal
      and parabasal/suprabasal cells. Transitional (cuboidal) and squamous epithelium
      in inverted papillomas comparably expressed CK7, CK8, CK18, and CK19. In addition
      CK13 was found in subluminal and surface cells. Immunoreactivity for CK5/14 and
      CK17 involved all layers of the epithelium. In nonpapillomatous nasal mucosa
      adjacent to inverted papillomas, CK expression in columnar (respiratory)
      epithelium exactly matched the findings in inverted papillomas. Transitional
      (cuboidal) and squamous epithelium in nonpaillomatous mucosa were negative for
      CK7, CK8, CK18, and CK19. CK13 was expressed in subluminal and surface cells.
      Immunoreactivity for CK5/14 and CK17 was restricted to basal and
      parabasal/suprabasal cells. Conclusively, transitional (cuboidal) and squamous
      epithelium in inverted papillomas but not in the adjacent mucosa coexpress CKs
      typical for columnar and squamous differentiation.

PMID- 11345841
TI  - Diffuse pulmonary disease caused by nontuberculous mycobacteria in
      immunocompetent people (hot tub lung).
AB  - The clinicopathologic spectrum of infections due to nontuberculous mycobacteria
      (NTM) includes cavitary disease, opportunistic infection, and nodular disease
      associated with bronchiectasis. We report a less well-described manifestation of
      NTM infection: 10 immunocompetent patients without preexisting bronchiectasis had
      radiographic evidence of diffuse infiltrative lung disease. The most common
      symptoms were dyspnea, cough, hypoxia, and fever. All 10 patients had used a hot
      tub. Histologic examination revealed exuberant nonnecrotizing, frequently
      bronchiolocentric, granulomatous inflammation in all cases. In 1 case,
      necrotizing granulomas were also noted. The inflammation often was associated
      with patchy chronic interstitial pneumonia and organization. Cultures revealed
      NTM in all cases (Mycobacterium avium complex in all but 1 case), but staining
      for acid-fast bacilli was positive in only 1 case. Four patients received
      corticosteroids alone for presumed hypersensitivity pneumonia, 4 were treated
      with antimycobacterial therapy, and 2 received both. All patients demonstrated
      significant improvement at the time of follow-up. These findings suggest that
      disease due to NTM may manifest as diffuse infiltrates in immunocompetent adults
      and that hot tub use may be an important risk factor for this disease pattern.

PMID- 11345842
TI  - Multiplex analysis of heterophil antibodies in patients with indeterminate HIV
      immunoassay results.
AB  - We hypothesized that heterophil antibodies reactive with animal proteins used in
      blot preparation caused nonspecific staining (NSS) on HIV Western blot (WB)
      studies, causing indeterminate results. We analyzed samples showing NSS on HIV WB
      using a multiplexed immunoassay to simultaneously measure IgG antibodies to
      animal IgG (bovine, goat, sheep, mouse) and bovine serum albumin. Heterophil
      antibodies reactive with IgG from several animal species were detected in 23
      (49%) of 47 samples showing NSS on HIV WB; 15 positive samples demonstrated
      antibodies to all 5 antigens. Similar IgG heterophil antibodies were detected in
      only 2 (8%) of 24 control samples. Of the HIV WB samples with a positive HIV-1
      enzyme-linked immunosorbent assay (ELISA) result at the time of WB testing
      (11/47), heterophil antibodies were found in 8 (73%) of 11. Preabsorption with
      bovine, goat, and sheep IgG removed heterophil antibodies detected by the
      multiplexed assay and, in some cases, eliminated reactivity in ELISA and WB
      testing. Heterophil antibodies are associated with indeterminate HIV immunoassay
      results and are an important cause of false-positive HIV ELISA results.
      Multiplexed immunoassays provide a powerful tool for screening patients for
      heterophil antibodies and resolving possible false-positive results.

PMID- 11345843
TI  - The content and distribution of troponin I, troponin T, myoglobin, and alpha
      hydroxybutyric acid dehydrogenase in the human heart.
AB  - We studied the content and distribution of heart-specific markers troponin I and
      troponin T in relation to conventional non-heart specific myoglobin and alpha
      hydroxybutyric acid dehydrogenase (HBD) in the hearts of 34 patients who died of
      various causes. Tissue was obtained from the right and left ventricles, the
      interventricular septum, and the right and left atria. We found significant
      differences in the contents expressed per gram wet weight tissue in the right and
      left ventricles for troponin I (by 1 of the 2 methods used), troponin T,
      myoglobin, and HBD and no differences per gram of protein. The biochemical
      contents per gram wet weight tissue and per gram protein were significantly lower
      in the right and left atria for all studied markers compared with the right and
      left ventricles. No significant differences were found in biochemical contents
      between the right and left atria. These findings imply that estimation of
      myocardial damage through cardiac markers levels in serum depends on the site of
      injury (atrium or ventricle). Comparison of myocardial injury among individuals
      using marker levels in serum is not reliable because of the varied ranges of
      markers in tissue contents.

PMID- 11345844
TI  - Reactive spindle cell nodules of the breast.

PMID- 11345845
TI  - Follicular lesions of the thyroid.

PMID- 11345846
TI  - Differentiating narcissistic and antisocial personality disorders.
AB  - The conceptual, clinical, and empirical overlap between the constructs of
      narcissistic personality disorder (NPD) and antisocial personality disorder
      (ASPD) is reviewed and their descriptive discriminability is investigated. Twenty
      four patients with NPD and 16 patients with ASPD were compared on 33
      characteristics for pathological narcissism assessed with the semistructured
      Diagnostic Interview for Narcissism. The results confirm a sufficiently broad
      array of similarities that the question of whether these categories should be
      kept separate (as they are in DSM-IV) is underscored. The results also indicate
      important areas of difference. The NPD sample was best discriminated from the
      ASPD sample by their grandiosity, that is, the tendency to exaggerate their
      talents, and to regard themselves as more unique and superior.

PMID- 11345847
TI  - Using DSM axis II information to predict outcome in short-term individual
      psychotherapy.
AB  - The present study considered three methods of using DSM Axis II information to
      examine the effect of personality disorder on outcome in two forms of short-term,
      individual psychotherapy (interpretive and supportive). The first method involved
      examining whether the presence of any personality disorder influenced treatment
      outcome. The second method involved examining the effect of the number of
      personality disorders on outcome. The third involved examining outcome for
      specific personality disorders. The study found that a diagnosis of any
      personality disorder did not influence the outcome of therapy. In contrast, the
      number of personality disorders was significantly related to outcome at post
      therapy and at 12-month follow-up. The findings indicated that a greater number
      of personality disorders was associated with less favorable outcome across both
      forms of therapy. This supports the notion that personality pathology is more
      severe when it involves a greater number of personality disorders. In an
      exploratory set of analyses, the study also found some evidence of differences in
      outcome for specific personality disorders.

PMID- 11345848
TI  - The contribution of temperament, childhood neglect, and abuse to the development
      of personality dysfunction: a comparison of three models.
AB  - We examined the contribution of temperament, childhood neglect, and abuse to the
      development of personality dysfunction as postulated in three different but
      correlated models of personality: the psychobiological, Vaillant's
      psychoanalytic, and DSM psychopathology models. Character, defense style, and
      personality disorder symptomatology (the dependent variables), and temperament,
      childhood neglect, and abuse (the independent variables) were assessed in 168
      depressed outpatients. High harm avoidance (temperament) tended to be the
      strongest and most consistent risk factor across the three models. Deficient
      parental care predicted personality dysfunction, however low care was not
      consistently predictive across all three models. Emotional/psychological abuse
      and actual physical abuse were risk factors for increasing personality disorder
      symptomatology only. Childhood sexual abuse was not as predictive of personality
      dysfunction as might be expected, thereby raising questions as to the importance
      placed on child sexual abuse as a general risk factor for personality
      psychopathology.

PMID- 11345850
TI  - Self-concept correlates of the personality disorders.
AB  - This study investigated the extent to which the DSM personality disorder
      dimensions are associated with discrete patterns of self-concept. Participants
      were 366 men and women who were receiving mental health services and who
      completed the Wisconsin Personality Disorders Inventory to assess the personality
      disorders and Benjamin's INTREX questionnaire to describe their "typical" self
      concepts. Although there was some overlap between categories, most were
      associated with fairly distinct patterns of self-concept. The disorders also
      clustered together in meaningful ways along the major axes of Benjamin's
      interpersonal model of the self-concept.

PMID- 11345849
TI  - The relationship between traumatic experiences, dissociation, and borderline
      personality pathology among male forensic patients and prisoners.
AB  - In the present study the relationship between traumatic experiences,
      dissociation, and borderline personality disorder pathology is examined in a
      group of 39 male forensic patients and 192 male prisoners. Sexual and emotional
      abuse are significantly more common among forensic patients than among prisoners.
      Patients also report a broader range of different kinds of traumas. Prisoners
      report significantly more dissociative symptoms. Analyses of the relationship of
      type of trauma on the one hand and dissociation and borderline personality
      pathology on the other show that sexual abuse is significantly associated with
      borderline personality pathology but not with dissociation among the patients. In
      the prison sample these associations are found only for familial but not
      extrafamilial sexual abuse. When the subjects are grouped on account of presence
      or absence of a borderline personality disorder, highly significant differences
      on dissociation are found between both groups. The results from this study lend
      support to the hypothesis that sexual abuse is not related to dissociative
      symptoms but merely to borderline personality pathology. Because most subjects in
      this study are not patients, these findings are not likely to be confounded by
      false memories of traumatic events that are recovered by psychotherapy.
      Furthermore, dissociative symptoms are found to be related to borderline
      personality pathology and not to the experience of traumatic events.

PMID- 11345851
TI  - The relationship between comorbid personality disorders and treatment received in
      patients with anxiety disorders.
AB  - Few studies have addressed the relationship between the presence of a comorbid
      personality disorder and the amount of psychiatric treatment received by patients
      with an Axis I disorder. This issue has not been studied in patients with anxiety
      disorders. In a prospective, naturalistic, longitudinal study of anxiety
      disorders, 526 subjects were assessed with the Personality Disorder Examination,
      and types of treatment received in 1991 and 1996 were identified. In 1991,
      compared to subjects without a personality disorder, subjects with a personality
      disorder were as likely to receive medication and they received a greater number
      of medications. Subjects with borderline personality disorder were more likely to
      receive heterocyclic antidepressants and interventions characteristic of
      psychodynamic psychotherapy and cognitive therapy; they also reported receiving a
      greater number of medications and types of psychosocial treatment than other
      subjects. In 1996, subjects with borderline personality disorder were more likely
      to receive psychodynamic interventions. These findings suggest that in patients
      with an anxiety disorder, the presence of a comorbid personality disorder is
      associated with receiving a greater number of medications but not with a greater
      likelihood of receiving pharmacologic or psychosocial treatment. However, the
      presence of borderline personality disorder is associated with a greater
      likelihood of receiving, and receiving a greater number of, certain types of
      somatic and psychosocial treatments.

PMID- 11345852
TI  - Schizotypal Personality Questionnaire-Brief: factor structure and convergent
      validity in inpatient adolescents.
AB  - We examined the internal consistency, factor structure, and validity of the
      Schizotypal Personality Questionnaire-Brief (SPQ-B). Two hundred thirty-seven
      psychiatrically hospitalized adolescents were administered the SPQ-B and a
      battery of well-established self-report instruments. The SPQ-B demonstrated
      adequate internal consistency. Exploratory factor analysis provided mixed support
      for the SPQ-B 3-factor structure of interpersonal deficits, cognitive-perceptual
      deficits, and disorganization. The Interpersonal and Cognitive-Perceptual
      subscales demonstrated convergent and discriminant relationships with other
      measures of interpersonal impairment and cognitive abnormalities. We concluded
      that the SPQ-B is a promising measure for evaluating schizotypal personality
      disorder features, specifically interpersonal and cognitive-perceptual deficits,
      with adolescent psychiatric inpatients.

PMID- 11345853
TI  - Examination of the screening properties of the personality diagnostic
      questionnaire 4+ (PDQ-4+) in a prison population.
AB  - There is a high prevalence of personality disorder in most prison populations.
      Many pass through the system undiagnosed. A screening instrument would improve
      identification. This study examined the screening properties of the Personality
      Diagnostic Questionnaire-4+ (PDQ-4+) in prisoners convicted of violent and sexual
      offenses. A sample of British prisoners completed the self-report PDQ-4+ and were
      interviewed using the Structured Clinical Interview for DSM-IV Axis II disorders.
      When used to generate a total score, the PDQ-4+ had an acceptable overall
      accuracy as measured by the area under the Receiver Operating Characteristics
      (ROC) curve. The PDQ-4+ appears to have the properties suitable for use as a
      screening instrument, particularly when screening for the presence or absence of
      personality disorder rather than for individual personality disorder categories.
      A graph is presented from which choices of cut-off score for different
      combinations of sensitivity and specificity can be made. A cut off total score of
      25 or above yielded near optimal sensitivity and specificity. The suggested cut
      off score for this population is lower than that previously suggested.

PMID- 11345854
TI  - 1971 status of private hospital beds.

PMID- 11345855
TI  - Incidence of hip fracture in Alaska Inuit people: 1979-89 and 1996-99.
AB  - Review of records of the Alaska Native Medical Center in Anchorage, Alaska show
      that the incidence of hip fracture in Inuit women over 64 years of age was higher
      than the incidence in white US women in 1979-89 and had increased farther by 1996
      99. The hip fracture incidence of Inuit men was higher than US men in 1996-99.

PMID- 11345856
TI  - Comparisons of Yupik infant growth measurements with NCHS/CDC reference data.
AB  - The National Center for Health Statistics/Centers for Disease Control and
      Prevention growth reference is routinely used to monitor Yupik infant growth
      although Yupiks are ethnically different from the population from which the
      reference was developed. To clarify interpretation of Yupik infant growth data
      for clinical practice and public health assessment, Yupik infant growth
      measurements were compared with this reference. From 1990 through 1992 a
      convenience survey of 555 Yupik infants was completed in pediatric clinics in the
      Yukon Kuskokwim Delta region of Alaska. Data was analyzed using Z-score
      distributions of height-for-age, weight-for-age, and weight-for-height and head
      circumference-for-age percentiles based on the growth reference. At birth, Yupik
      neonates had significantly greater height-for-age and weight-for-age than the
      National Center for Health Statistics/Centers for Disease Control and Prevention
      reference. Between 1 and 12 months, Yupik infants had significantly greater
      weight-for-age, weight-for-height, and head circumference-for-age than the growth
      reference.

PMID- 11345857
TI  - [The dog: is it the future of cancer genetics?].

PMID- 11345858
TI  - [Women in medicine: women's access to competitive examinations in Paris hospitals
      at the end of the 19th century].

PMID- 11345859
TI  - [Septic shock].
AB  - Septic shock is the most severe systemic inflammatory response to infection.
      Despite recent progress in prevention and critical care therapy, this syndrome is
      the most common cause of death in intensive care units. Major advances have been
      realized recently in the understanding of septic shock. Cellular receptors
      involved in bacterial recognition have been identified as Toll-like receptors.
      After bacterial challenge, these receptors become activated and initiate in
      septic shock patients a biphasic immunological response associated with
      coagulation disorders. Genetic variability among humans and their predisposition
      towards pathologic inflammatory responses have also been demonstrated. These
      current views on the pathophysiological aspects of septic shock open new
      therapeutic perspectives which should change the prognosis of this syndrome.

PMID- 11345860
TI  - [Purulent meningitis].
AB  - Purulent meningitis is a bacterial infection of the subarachnoid space. It
      constitutes a diagnostic and therapeutic emergency. The vital and functional
      prognosis is always engaged and depends on the rapidity and the adequacy of
      management. Treatment is based on a bactericidal antibiotic treatment which is at
      first empirically prescribed, on the basis of the underlying condition, the
      clinical examination and the epidemiological context, and then adjusted according
      to the micro-organism isolated from the cerebrospinal fluid. The recent emergence
      and increase of penicillin-resistant Streptococcus pneumoniae has led to a
      modification of antibiotic guidelines.

PMID- 11345861
TI  - [Meningoencephalitis].
AB  - There are many infectious agents that may be responsible for meningoencephalitis.
      Historical data, clinical examination, analysis of cerebrospinal fluid and
      imaging often do not make it possible to retain initially a precise diagnostic
      orientation. In emergency, it is essential to seek the infectious causes imposing
      a specific treatment. Herpes simplex virus encephalitis is rare but it must be be
      always searched and a presumptive treatment must be started because of the
      spontaneously fatal evolution or heavy neurological sequelae. Hypothesis of
      Listeria meningoencephalitis being often impossible to eliminate from the start,
      anti-biotherapy must also be started immediately. Tuberculous meningoencephalitis
      must be evoked according to the ground. Other uncommon curable infectious causes
      are to be considered according to the context.

PMID- 11345862
TI  - [Severe community-acquired pneumonia].
AB  - Community-acquired pneumonia is severe when hospitalisation is required. The
      diagnosis is based on pulmonary involvement (chest radiography) associated with
      vital signs abnormalities (mental status, temperature, blood pressure and
      ventilatory rate) or immunosuppression (neoplastic diseases). No specific
      causative pathogen could be incriminated. S. pneumoniae is the main causative
      pathogen. Prognosis-related factors are numerous. Among them, the effectiveness
      of the initial antimicrobial therapy appears as the main factor directly related
      to the medical intervention. First-line antimicrobial therapy, instituted as soon
      as possible, is empirical and must, always, be effective against S. pneumoniae.
      For pneumonia requiring admission into ICU, a wider antimicrobial spectrum based
      on antimicrobial combination is used. Mortality rates varying from 3 to 30% could
      be early predicted by specific prognostic indices.

PMID- 11345863
TI  - [Acute infectious endocarditis].
AB  - Acute infective endocarditis are due to highly virulent microorganisms, such as
      Staphylococcus aureus, able to invade normal endocardium, causing fulminant local
      damages (valvular destruction) as well as general damages (sepsis, metastasis),
      so that clinical manifestations are usually dramatic. Empirical antimicrobial
      therapy must be given immediately, using combinations active against the most
      commonly encountered pathogens. Other treatments are frequently necessary:
      medical therapy for heart failure, surgery of valvular reconstruction or
      replacement, respiratory assistance and other supportive measures. Such
      management requires cooperation of several disciplines.

PMID- 11345864
TI  - [Dermo-hypodermitis and necrotizing fasciitis].
AB  - Acute gangrenous dermo-hypodermitis and necrotizing fasciitis are potentially
      life-threatening infections of skin and soft tissues, which may be difficult to
      recognize at an early stage. A combination of local signs (erythema, mottling,
      bullous formation) and of symptoms suggestive of sepsis should prompt early
      suspicion and therapeutic intervention. Group A streptococci remain the major
      pathogen involved in necrotizing fasciitis involving extremities, following minor
      trauma or surgery, and sometimes apparently spontaneously. The most severe form
      is streptococcal toxic shock syndrome, where production of exotoxins
      (superantigens) is a major factor contributing to the severity of the syndrome. A
      number of other pathogens, often combined in mixed aerobic-anaerobic infections
      may be involved, especially in post-surgical and perineal gangrene. Surgery
      remains the mainstay of therapy, and should be considered as soon as the clinical
      suspicion arises. Antibiotic therapy is based on penicillins (penicillin G for
      streptococcal gangrene, or beta-lactamases penicillins in polymicrobial
      infections). New therapeutic approaches (clindamycin and immunoglobulins) may be
      useful in streptococcal toxic shock. The prognosis appears to have improved in
      recent years with early therapeutic intervention, but remains largely dependent
      on the severity of the septic response and underlying diseases.

PMID- 11345865
TI  - [Fever in the neutropenic patient].
AB  - The neutropenic patient, whatever the cause of neutropenia (drug related,
      secondary to marrow involvement by malignant disease or to cytotoxic treatment)
      is at high risk of bacterial and fungal infection. The first symptom (and often
      the only one) of infection is fever. The guidelines for management of the febrile
      neutropenic patient are precise and simple and have been widely accepted for more
      than 30 years allowing a dramatic decrease of the infectious mortality during
      episodes of neutropenia.

PMID- 11345866
TI  - [Severe malaria].
AB  - Falciparum malaria remains a major killer in developing countries, particularly
      for African children. Moreover, France is the leading European country in term of
      incidence of imported malaria. Parasitized erythrocytes, which can form rosettes
      or auto-agglutinate, are sequestrated in the deep microvasculature and stick to
      activated endothelium by the mean of various receptors. Activation of T
      lymphocytes and macrophages induces secretion of proinflammatory cytokines,
      including tumour necrosis factor, which contributes to severe disease. However,
      the pathophysiology of coma remains poorly understood. In nonimmune adults,
      besides cerebral malaria, pictures of severe sepsis with shock, acute renal
      failure and respiratory distress syndrome are common. Although chemotherapy of
      malaria is challenged by the continuing evolution of antimalarial resistance,
      quinine remains the first-line drug for severe imported disease. In addition,
      early symptomatic management in the intensive care unit setting is of paramount
      importance. Prevention of severe imported malaria lays on prophylactic measures
      during travel, as well as adequate management of uncomplicated disease after
      return. In developing countries, early and adequate treatment of uncomplicated
      disease using cheap alternatives to classical compounds should contribute to
      "roll back" malaria, particularly in sub-Saharan Africa.

PMID- 11345867
TI  - [The social responsibility of medical faculty].

PMID- 11345868
TI  - [Narcotic addiction. Epidemiology, management modalities, complications,
      diagnosis and treatment of overdoses; clinical symptoms and withdrawal syndrome].

PMID- 11345869
TI  - [The dose-response relationship of prescription drugs].

PMID- 11345870
TI  - [Hyperkalemia. Etiology, physiopathology, diagnosis, treatment].

PMID- 11345872
TI  - [Cardiomyopathies. Symptoms, prognosis, treatment].

PMID- 11345871
TI  - [Rheumatoid purpura in children and adults. Diagnosis, prognosis].

PMID- 11345873
TI  - Medicare FAQs.

PMID- 11345874
TI  - A new administration and health care issues: temporarily sidelined?

PMID- 11345875
TI  - Beyond the malaise of American medicine.
AB  - Over the past two decades, physicians have suffered declines in real income,
      community standing, and of collegiality. Physicians must not view themselves
      solely as victims of the sweeping changes in current medical care delivery. They
      have both the opportunity and the duty to reassert their true role as
      compassionate conveyors of the science and the art of medicine. This article
      explores the historic trends that have led to our current state. It also explores
      the exciting possibilities open to doctors to assume a renewed elevated status
      that both they and their patients yearn for.

PMID- 11345876
TI  - The physician-hospice partnership: expanding opportunities to improve end-of-life
      care.
AB  - People living with a life-limiting illness require expert medical care to control
      often debilitating symptoms. Beyond physical care issues, people at the end of
      life also need emotional and spiritual support for themselves and their loved
      ones. Hospices offer a range of services via an interdisciplinary team to meet
      the specialized needs of people at the end of life. This article will explore the
      physician-hospice partnership and the benefits to patients, family caregivers,
      and physicians when hospice care is accessed early in the dying process. Benefits
      of interdisciplinary, patient/family-directed care will be discussed. The range
      of palliative services being offered by many hospices will also be presented as a
      mechanism to increase access to end-of-life services for patients and family
      caregivers.

PMID- 11345877
TI  - Hospice care and the Medicare Hospice Benefit.

PMID- 11345878
TI  - Practice financing options for small to mid-sized medical practices.
AB  - In today's competitive marketplace, finding and using capital in the most
      effective manner can help bring greater economic success to medical practices.
      This article focuses on the most common capital needs of practices ranging in
      size from solo practices to 25 physicians--practice acquisition, real estate,
      operating cash needs, and medical equipment--and the types of capital providers
      for these size practices--health care financing firms, banks, and equipment
      leasing companies. Interviews with various capital finding providers and various
      research information, including a 1998 study commissioned by AMA Solutions, Inc.
      (a subsidiary of the American Medical Association) form the basis for the
      information provided.

PMID- 11345879
TI  - New faster processing of claims under ERISA health plans.

PMID- 11345880
TI  - How to make staff training more effective.
AB  - An employee-training program offers many benefits both to employees and to the
      professional practice. However, it takes time, effort, and know-how to structure
      an effective training program. This article offers guidelines for staff training
      and explores specific training techniques that work. Among these are narrated
      demonstration, role-playing, flashcard training, study motivation exams, and
      tuition reimbursement programs. In addition, this article offers a script of a
      sample role-playing session.

PMID- 11345881
TI  - Complexities of the multi-specialty surgical patient.

PMID- 11345882
TI  - The likely future for national malpractice premiums.

PMID- 11345884
TI  - Principles of good medical record documentation.
AB  - Although the world of medicine seems to be changing and progressing with each
      day, one thing that has not changed is the need for good documentation. The
      medical record of today does not only reflect your care of the patient, but has
      become a communication tool to a wide variety of players. Everyone seems to
      looking at your records, from colleagues to HMOs, and in the worst-case scenario,
      a plaintiff's attorney. This article will help show why good documentation is so
      important not only for good medical care, but if needed, as a defense tool if
      faced with a medical malpractice claim.

PMID- 11345883
TI  - U.S. government's guide for practice compliance programs.

PMID- 11345885
TI  - Peer review: confidentiality and privilege--Part Two.

PMID- 11345886
TI  - The ever imminent electronic medical record.
AB  - The electronic medical record (EMR) remains an elusive holy grail. The reasons
      include limited electronic and voice recognition capabilities, as well as
      established medical practice patterns. There is also some question as to the time
      and cost efficacy of inputs into an EMR.

PMID- 11345887
TI  - Physician recruitment websites.
AB  - Searching for the ideal job can be a difficult task. The challenge is often made
      more difficult when candidates use the Internet without the background
      information they need. This article discusses the four categories of physician
      recruitment websites (Association Directories, Journal Classified Ads, Recruiting
      Firms/Departments, and Database Clearinghouses) and lists several useful URLs to
      visit as you begin your search. In an upcoming issue, the author will address the
      future of physician recruitment websites.

PMID- 11345888
TI  - Wireless invasion: health care's evolution to wireless connectivity.
AB  - Health care is adapting to embrace wireless solutions. Today's physicians are
      seeing more patients at more locations in less time, which creates a significant
      need to implement a timesaving, cost-effective solution and provide the best
      possible care in a secure environment. Mobility, patient information security and
      confidentiality, HIPAA regulations, disparate legacy systems, and the need for
      immediate access to critical health care information all necessitate
      implementation of a technology system designed to alleviate these complications,
      improve medical outcomes, and streamline administrative processes. Wireless
      technology is proven to provide timely, accurate, and secure exchange of patient
      information. WirelessMD offers a comprehensive solution for physician practices
      to increase efficiency and enhance patient care.

PMID- 11345889
TI  - Deferred compensation.

PMID- 11345890
TI  - Help is on its way: Congress proposes measures to deal with nursing home staffing
      crisis.

PMID- 11345891
TI  - Is your facility up to snuff on fire safety, physical plant issues?

PMID- 11345892
TI  - HCFA releases revised survey protocols, guidance to surveyors.

PMID- 11345893
TI  - Year 2000--HCFA issues eleven advisory opinions.

PMID- 11345894
TI  - Recent False Claims Act and fraud and abuse statute cases and issuances.
AB  - Each of these cases and issuances is likely to substantially impact the health
      care lawyer. Specifically, the factual situation in the advisory opinion is
      likely to be duplicated extensively. Further, in False Claims Act defense
      situations, the defense that senior level management was not aware of the actions
      of a lower-level employee will likely be extensively tried (potentially with
      varying degrees of success).

PMID- 11345895
TI  - Stark Act regulations: an overview.

PMID- 11345896
TI  - Green tea: biochemical and biological basis for health benefits.

PMID- 11345897
TI  - Three-Dimensional Organization of the aquaporin water channel: what can structure
      tell us about function?

PMID- 11345898
TI  - Cytostatic p21 G protein-activated protein kinase gamma-PAK.
AB  - The p21-activated protein kinase gamma-PAK, also known as PAK2, has very
      different properties from the other two highly conserved isoforms of the PAK
      family, alpha-PAK (PAK1) and beta-PAK (PAK3). gamma-PAK has cytostatic activity,
      as shown by inhibition of cleavage of early frog embryos following microinjection
      of gamma-PAK and by inhibition of growth when expressed in mammalian cells. gamma
      PAK is activated in response to a variety of stresses including radiation- and
      chemically-induced DNA damage, hyperosmolarity, addition of sphingosine, serum
      starvation, and contact inhibition. Activation occurs through at least two
      signaling pathways, depending on the type of stress, one of which requires
      phosphoinositide 3-kinase and/or tyrosine kinase activity. During apoptosis gamma
      PAK is cleaved by caspase 3 and activated and appears to have a role in the
      apoptotic response. gamma-PAK is present in the cytosol, associated with the
      membrane and in secretory granules. A wide variety of substrates have been
      identified for gamma-PAK. We propose gamma-PAK may be involved in coordinating
      the stress response, possibly in conjunction with other stress response proteins.

PMID- 11345899
TI  - Androgen receptors and their biology.

PMID- 11345900
TI  - Transcriptional activation of genes by 17 beta-estradiol through estrogen
      receptor-Sp1 interactions.
AB  - Estrogen receptor-alpha (ER alpha) is a ligand-activated transcription factor and
      a member of the nuclear receptor superfamily. The classic mechanism of ER alpha
      action is associated with estrogen-induced formation of a nuclear ER alpha
      homodimer, binding to 5'-regulatory estrogen response elements (EREs) in target
      gene promoters, interaction with other nuclear proteins, and general
      transcription factors to activate gene expression. ER alpha also interacts with
      Sp1 protein to transactivate genes through binding Sp1(N)xERE or Sp1(N)xERE half
      site (1/2) motifs where both ER alpha and Sp1 bind DNA elements. Activation
      through Sp1(N)xERE1/2 requires interactions of both proteins with their cognate
      DNA elements as well as additional nuclear factors to form a functional ER
      alpha/Sp1-DNA complex. Recent studies also show that ER alpha and Sp1 physically
      interact and ER alpha preferentially binds to the C-terminal DNA-binding domain
      of Sp1 protein. Moreover, ER alpha/Sp1 can activate transcription from a
      consensus GC-rich Sp1 binding site in transient transfection studies in MCF-7
      human breast cancer cells, and this response is also observed with ER alpha
      variants that do not contain the DNA-binding domain. Several genes that are
      induced by estrogens in MCF-7 cells are activated through one or more GC-rich
      sites in their regulatory regions and these include the cathepsin D, E2F1, bcl-2,
      c-fos, adenosine deaminase, insulinlike growth factor binding protein 4, and
      retinoic acid receptor alpha 1 genes. ER alpha/Sp1 and ER beta/Sp1 action is
      dependent on ligand structure and cell context and ER beta/Sp1 is primarily
      associated with decreased ligand-dependent gene expression. ER alpha/Sp1, like ER
      alpha/AP1, represents a pathway for hormone activation of genes in which the
      receptor does not bind DNA, and results of ongoing studies suggest that ER
      alpha/Sp1 plays an important role in transcriptional activation of multiple
      growth regulatory genes in breast cancer cells.

PMID- 11345901
TI  - Drug discovery and the intracellular receptor family.
AB  - Drug discovery using intracellular receptors (IRs) as targets presents its own
      set of unique complications and advantages. The natural ligands for these
      receptors are, in many cases, already used as drugs. To effectively exploit these
      targets, newer molecules must have either increased receptor selectivity or
      increased tissue or gene selectivity to reduce side effects. The search for these
      molecules will yield new therapeutics as well as new insights into the mechanism
      of action of these receptors and their ligands.

PMID- 11345902
TI  - Proteins regulating the biosynthesis and inactivation of neuromodulatory fatty
      acid amides.
AB  - Fatty acid amides (FAAs) represent a growing family of biologically active lipids
      implicated in a diverse range of cellular and physiological processes. At
      present, two general types of fatty acid amides, the N-acylethanolamines (NAEs)
      and the fatty acid primary amides (FAPAs), have been identified as potential
      physiological neuromodulators/neurotransmitters in mammals. Representative
      members of these two subfamilies include the endocannabinoid NAE anandamide and
      the sleep-inducing FAPA oleamide. In this Chapter, molecular mechanisms proposed
      for the biosynthesis and inactivation of FAAs are critically evaluated, with an
      emphasis placed on the biochemical and cell biological properties of proteins
      thought to mediate these processes.

PMID- 11345903
TI  - Coordinated care put to the test in bold Medicare demo.

PMID- 11345904
TI  - HCFA demo sites offer a smorgasbord of managed care innovation.
AB  - Diverse approaches to DM and CM are ready for HCFA's scrutiny. In selecting sites
      for its ambitious demonstration project on coordinated care, HCFA searched far
      and wide for disease management and case management programs that could produce
      positive clinical and financial results, targeting chronically ill Medicare
      beneficiaries. See how two of these sites aim to prove that their vastly
      different approaches will thrive under a mixture of managed care and fee-for
      service.

PMID- 11345905
TI  - Successful DM efforts make the case for investment in hypertension control.
AB  - Focus like a laser-beam on hypertension. Why? Because data consistently show that
      only a small percentage of people diagnosed with this chronic condition are
      adequately controlled. Despite the fact that this is an obvious opportunity for
      improvement, few organizations have launched DM efforts specifically targeting
      hypertension, primarily because of the difficulty inherent in predicting ROI.
      However, DMA reviews two approaches that are getting notable results.

PMID- 11345906
TI  - Pioneering organizations expect financial and clinical benefits from 'online
      encounters'.
AB  - Take advantage of e-communications to boost care of the chronically ill. Experts
      have long anticipated the day when patients would be communicating directly with
      their physicians via the web. And now a few pioneering organizations have made
      that prediction a reality. The obstacles to embarking on such a course are
      numerous, with concerns over such issues as security and reimbursement looming
      large. However, the potential benefits--particularly for chronically ill patients
      -are just too compelling to ignore.

PMID- 11345907
TI  - Swarm intelligence. A whole new way to think about business.
AB  - What do ants and bees have to do with business? A great deal, it turns out.
      Individually, social insects are only minimally intelligent, and their work
      together is largely self-organized and unsupervised. Yet collectively they're
      capable of finding highly efficient solutions to difficult problems and can adapt
      automatically to changing environments. Over the past 20 years, the authors and
      other researchers have developed rigorous mathematical models to describe this
      phenomenon, which has been dubbed "swarm intelligence," and they are now applying
      them to business. Their research has already helped several companies develop
      more efficient ways to schedule factory equipment, divide tasks among workers,
      organize people, and even plot strategy. Emulating the way ants find the shortest
      path to a new food supply, for example, has led researchers at Hewlett-Packard to
      develop software programs that can find the most efficient way to route phone
      traffic over a telecommunications network. South-west Airlines has used a similar
      model to efficiently route cargo. To allocate labor, honeybees appear to follow
      one simple but powerful rule--they seem to specialize in a particular activity
      unless they perceive an important need to perform another function. Using that
      model, researchers at Northwestern University have devised a system for painting
      trucks that can automatically adapt to changing conditions. In the future, the
      authors speculate, a company might structure its entire business using the
      principles of swarm intelligence. The result, they believe, would be the ultimate
      self-organizing enterprise--one that could adapt quickly and instinctively to
      fast-changing markets.

PMID- 11345908
TI  - Leading through rough times. An interview with Novell's Eric Schmidt. Interview
      by Bronwyn Fryer.
AB  - Few large companies have soared as high, sunk as low, and struggled as long as
      the 18-year-old networking software maker Novell. For years, the company
      dominated the market for local area networks, but by 1997, it had faltered due to
      misguided acquisitions, product missteps, and large unsold inventories. That's
      when Eric Schmidt arrived from Sun Microsystems to take over as Novell's third
      CEO. He turned the company around with a deft combination of cost reductions,
      divestitures, and new product rollouts, and by 1998, it was back in the black.
      Unfortunately, the good times didn't last, and like most technology companies,
      Novell is once again struggling with a slowdown in demand. But Schmidt is
      optimistic about returning Novell to good health, and his strategies suggest ways
      for other organizations to handle themselves during downturns. He counsels
      against being overly cautious during such times. It may be necessary to eliminate
      excess inventory, cut costs, and reduce the size of the staff and the management
      team in order to stabilize a company. Working to retain those employees whom he
      calls the "smart people" and keeping them motivated will have long-term payoffs.
      Further, Schmidt says it is necessary to acknowledge and overcome a "culture of
      fear," the deadening environment of cynicism in which employees suppress thoughts
      and feelings because they're worried about layoffs. His additional advice: keep
      new products coming out to sustain the interest of customers and the press, pay
      attention to your cash position, stay focused on your desired outcomes, and take
      heart from other industry leaders.

PMID- 11345909
TI  - Four rules for taking your message to Wall Street.
AB  - Managers fail to communicate effectively with Wall Street for all sorts of
      reasons. But neglecting the investment community--particularly the analysts whose
      opinions shape the market and whose recommendations often make or break a
      company's share price--can knock the most carefully conceived and brilliantly
      executed strategy off course. The companies that struggle the most with providing
      good information to analysts are those in rapidly evolving industries, where the
      gap between traditional performance metrics and economic realities is at its
      widest. In these industries, a company's strategy and the variables that govern
      its performance can change radically in a short time. What's more, the metrics
      used to report performance often fail to capture the drivers of value in today's
      information economy. Few accounting measures are helpful when it comes to
      assessing the intangible assets--knowledge, skilled employees, and so forth--on
      which many of today's fastest-growing companies build their strategies. According
      to Amy Hutton, an associate professor at Harvard Business School, there are four
      basic rules for clear communications with Wall Street. First, make sure that your
      company's financial reporting reflects your strategy as closely as possible.
      Second, popularize the nonfinancial metrics that best predict--and flatter--the
      performance of your businesses. Third, appoint managers with recognized
      credibility to your strategic operations. Finally, cultivate the market experts
      who cover the industries in which you seek to compete. Hutton shows how AOL
      successfully followed these rules as it significantly changed its strategic
      direction and competitive arena.

PMID- 11345910
TI  - How fast can your company afford to grow?
AB  - Everyone knows that starting a business requires cash, and growing a business
      requires even more. But few people understand that a profitable company that
      tries to grow too fast can run out of cash even if its products are great
      successes. So a big challenge for managers of any growing concern is to strike
      the proper balance between consuming cash and generating it. Authors Neil
      Churchill and John Mullins offer a framework to help identify and manage the
      level of growth that a company's cash flow can support. They present a formula to
      calculate an organization's self-financeable growth (SFG) rate, taking into
      account three critical factors: a company's operating cash cycle--the amount of
      time the company's money is tied up in inventory and other current assets before
      customers pay for goods and services; the amount of cash needed to finance each
      dollar of sales; and the amount of cash generated by each dollar of sales. The
      authors offer a detailed hypothetical example that carefully considers these
      three factors; they then illustrate how a company can influence its SFG rate by
      carefully managing some combination of those factors--that is, some mix of
      speeding cash flow, reducing costs, and raising prices. They expand on the
      original example by showing how to include income taxes and depreciation; plan
      for asset replacement; and identify which one of multiple product lines holds the
      greatest growth potential. The authors also discuss how various kinds of
      businesses--manufacturing firms, importers, and service companies--differ greatly
      in their abilities to finance growth from internally generated funds.

PMID- 11345911
TI  - When salaries aren't secret.
AB  - No one seemed to think Treece McDavitt was a malevolent employee. "Just
      mischievous," one person said. Whatever her motivation, the day before Treece was
      to leave RightNow!, an off-price women's fashion retailer, the 26-year-old
      computer wizard accessed HR's files and e-mailed employees' salaries to the
      entire staff. Now everyone knows what everyone else is making; they are either
      infuriated that they are making too little or embarrassed that they are making
      too much. Salary disparities are out there for everyone to see, and CEO Hank
      Adamson has to do something to smooth things over. Hank's trusted advisers talk
      extensively with the CEO about his options, ultimately coming down on two sides.
      Charlie Herald, vice president of human resources, takes a "You get a lemon, you
      make lemonade" approach: keep making the salaries public to ensure fairness and
      to push employees to higher performance, he advises. Meanwhile, CFO Harriet Duval
      sees the need for damage control: apologize, clean up the company's compensation
      system, and continue to keep--or at least try to keep--salaries private, she
      says. Should Hank side with Charlie or Harriet? Or perhaps find a compromise
      between their two views? What should he do about this serious salary debacle?
      Four commentators offer their advice on the problem presented in this fictional
      case study.

PMID- 11345912
TI  - A reading list for Bill Gates--and you. A conversation with literary critic
      Harold Bloom. Interview by Diane L. Coutu.
AB  - In today's technology-driven world, who has time to pick up a 400-page novel?
      Most executives don't--they have urgent e-mails to answer, training seminars to
      attend, meetings to lead, and trade publications to scan. But according to Harold
      Bloom, one of America's most influential scholars, they should make time in their
      hectic schedules to read great works. In a wide-ranging conversation with HBR
      senior editor Diane Coutu, Bloom discusses the importance of literature: every
      individual--regardless of profession--needs to stretch his or her mind and
      reflect now and again on the human condition. "By reading great imaginative
      literature, you can prepare yourself for surprise and even get a kind of strength
      that welcomes and exploits the unexpected," he says. Because there are so many
      great works and there is so little time, Bloom presents a reading list for busy
      executives. Shakespeare's King Lear can teach businesspeople about change. Ralph
      Waldo Emerson's essays capture the ethos of the American spirit--individualism
      and inventiveness. Bloom says Sigmund Freud's conceptions "form the only Western
      mythology that contemporary intellectuals have in common." And people will never
      fully understand some aspects of themselves until they read Miguel de Cervantes's
      Don Quixote. In short, Bloom believes the humanities have much to offer
      businesspeople: great books broaden their awareness and their range of
      sensibility, he says. But reading literature will not make businesspeople more
      moral, he cautions. Bloom also discusses other topics such as how to read well,
      the state of popular fiction, the role of irony, and the subject of change.

PMID- 11345913
TI  - Transforming corner-office strategy into frontline action.
AB  - When CEOs push decision making out to the far reaches of an organization, good
      things happen: fleeting business opportunities are seized quickly and workers are
      motivated to innovate and take risks. But it's tricky to achieve both
      decentralized decision making and coherent strategic action at a company. If
      everyone is a decision maker, things can spin out of control. In this article,
      Bain consultants Orit Gadiesh and James Gilbert explore the concept of the
      strategic principle--a memorable and actionable phrase that distills a company's
      corporate strategy into its unique essence and communicates it across an
      organization. If it's devised and disseminated properly, a strategic principle
      can empower employees to seize business opportunities but also focus everyone in
      an organization--executives and line managers alike--on the same strategic
      objectives. The authors outline the three defining characteristics of a good
      strategic principle--it should force trade-offs between competing resource
      demands, it should serve as a test for the strategic soundness of a particular
      action, and it should set clear boundaries for employees to operate within even
      as it grants them freedom to experiment. They explain how managers can create a
      strategic principle, how they should test it, and when they should revisit it.
      The authors present real-world examples of how companies use their strategic
      principles. For instance, they describe how South-west Airlines stopped flying to
      Denver after it measured the high costs of providing flight service in that part
      of the country against its strategic principle of offering customers short-haul
      air travel at fares competitive with the cost of automobile travel. This tool is
      increasingly useful in today's rapidly changing business environment, the authors
      conclude, and it is likely to become even more crucial to corporate success.

PMID- 11345914
TI  - Get inside the lives of your customers.
AB  - Many companies have become adept at the art of customer relationship management.
      They've collected mountains of data on preferences and behavior, divided buyers
      into ever-finer segments, and refined their products, services, and marketing
      pitches. But all too often those efforts are too narrow--they concentrate only on
      the points where the customer comes into contact with the company. Few businesses
      have bothered to look at what the author calls the customer scenario--the broad
      context in which customers select, buy, and use products and services. As a
      result, consultant Patricia Seybold maintains, they've routinely missed chances
      to deepen loyalty and expand sales. In this article, the author shows how
      effective three very different companies have been at using customer scenarios as
      the centerpiece of their marketing plans. Chip maker National Semiconductor
      looked beyond the purchasing agents that buy in bulk to find ways to make it
      easier for engineers to design National's components into their specifications
      for mobile telephones. Each time they do so, it translates into millions of
      dollars in orders. By developing a customer scenario that describes how people
      actually shop for groceries, Tesco learned the importance of decentralizing its
      Web shopping site and how the extra costs of decentralization could be outweighed
      by the higher profit margins on-line customers generate. And Buzzsaw.com used
      customer scenarios as the basis for its entire business. It has used the Web to
      create a better way for the dozens of participants in a construction project to
      share their drawings and manage their projects. Seybold lays out the steps
      managers can take to develop their own customer scenarios. By thinking broadly
      about the challenges your customers face, she suggests, you can almost always
      find ways to make their lives easier--and thus earn their loyalty.

PMID- 11345915
TI  - Lead from the center. How to manage divisions dynamically.
AB  - Conventional wisdom holds that a company's divisions should be given almost total
      autonomy--especially under conditions of uncertainty--because they are closer to
      emerging technologies, customers, and competitors than corporate headquarters
      could ever be. But research from Michael Raynor and Joseph Bower suggests that
      the corporate office should be more, not less, directive in turbulent markets.
      Rapid changes in an industry make it difficult to predict where and when
      synergies among divisions might emerge. With so many possibilities and such
      uncertainty, companies can't afford to sacrifice their ability to flexibly
      execute business strategy. Corporate headquarters must play an active role in
      defining the scope of division-level strategy, the authors say, so that divisions
      do not act in ways that undermine opportunities to collaborate in the future. But
      neither can companies afford to sacrifice the competitiveness of their divisions
      as stand-alone businesses. In creating corporate-level strategic flexibility, a
      corporate office must balance the need for divisional autonomy now with the
      potential need for cooperation in the future. Through an examination of four
      corporations--Sprint, WPP, Teradyne, and Viacom--the authors challenge
      traditional approaches to diversification in which a company's divisions are
      either related (they share resources and collaborate) or unrelated (they compete
      for resources and operate as stand-alone businesses). They argue that companies
      should adopt a dynamic approach to cooperation among divisions, enabling varying
      degrees of relatedness between divisions depending on strategic circumstances.
      The authors offer four tactics to help executives manage divisions dynamically.

PMID- 11345916
TI  - Facility profile. Merged mission reaps big rewards. University of Miami/Jackson
      Memorial Hospital, Mental Health Hospital Center.

PMID- 11345917
TI  - E-commerce is here. Are you buying?

PMID- 11345918
TI  - Be prepared! Coping with floods, fires, quakes and other disasters.

PMID- 11345919
TI  - Safe & sound. A systematic approach to preventing infant abductions.

PMID- 11345920
TI  - Putting patients first. NFPA standards provide technical guidance for ensuring
      safety.

PMID- 11345922
TI  - Lucretia's view: an interview with Lucretia W. McClure about medical reference
      through the years, February 25, 2000. Interview by Nancy W. Clemmons.
AB  - Lucretia W. McClure is one of the most respected figures in the field of medical
      librarianship. During an interview, she reminisces about important events and
      changes in librarians' work, users, and services over the past thirty-five years.
      She also gives her perspective about the impact of computer technology on
      reference services. Finally, she urges reference librarians to take action to
      shape their future.

PMID- 11345921
TI  - Time to go green! H2E program can provide environmental and financial benefits.

PMID- 11345923
TI  - First-year medical students' impressions of the Internet.
AB  - Physicians are becoming aware of the World Wide Web as a resource for medical
      information. In spring 1999, first-year students at the University of
      Louisville's School of Medicine were given an assignment to review and evaluate
      Internet search engines and directories, medicine-specific search engines and
      meta lists, and health-related Web sites. Students found that general search
      engines were easier to learn and use and produced better results than either meta
      medical sites or medicine-specific search engines. Students were very severe in
      judging the quality of health-related Web sites. Our students' impressions are
      compared to those of physicians in similar studies. Solutions to the problems of
      searching the Web for health information are reviewed.

PMID- 11345924
TI  - Books@Ovid: a product review.
AB  - Books@Ovid is a full-text database of clinical textbooks published by Lippincott,
      Williams and Wilkins, and McGraw-Hill. It is distributed by Ovid Technologies. In
      addition to discussing the search environment for Books@Ovid, this paper
      discusses its online help, indexes, and content, in terms of both coverage and
      updates. How this product competes with its counterparts in print is also treated
      in the discussion.

PMID- 11345925
TI  - No more tours: how library tours of the past become today's celebrations.
AB  - In 1999, Northwestern University's Galter Health Sciences Library redesigned the
      library orientation program for first-year medical students. Surveys indicated
      tours were ineffective and students retained little of the information presented.
      Furthermore, the tour was not related to the student's curriculum and did not
      reinforce their learning objectives. As a replacement, the library staff
      developed a self-directed two-hour library open house. Stations throughout the
      library showcased the library staff, services, and resources, focusing on the
      first-year student curriculum. A follow-up survey found this redesign more useful
      and relevant to the students' course work, indicating libraries should be
      creating more interactive tours for students allowing them to learn actively.

PMID- 11345926
TI  - Thread your way through ISI's Web of Science <http://www.webofscience.com>.

PMID- 11345927
TI  - Internet resources for Tibetan medicine.
AB  - Tibetan medicine has a history of over one thousand years. With the recent
      fascination with Tibet and Tibetan culture, Tibetan medicine is receiving greater
      attention from the public, scholars, and the media. In the past few years,
      researchers and practitioners of Tibetan medicine have established a presence on
      the Internet, evident through Web sites and discussion groups. This paper
      presents a sampling of valuable resources about Tibetan medicine readily
      accessible on the Internet. The selected sites were evaluated on the basis of
      quality and quantity of information, authoritativeness, currency of material,
      quality of links, and navigability.

PMID- 11345928
TI  - Current environment of hospital library reference: Part 2--Trends for the future
      of reference. Interview by Cheryl R. Dee and Kay E. Wellik.

PMID- 11345929
TI  - Preparing staff to work at a single service desk.

PMID- 11345930
TI  - Bolster risk assessment, adjustment efforts using ETGs (episode treatment
      groups).

PMID- 11345931
TI  - Hawaii insurer turns to risk sharing disease management initiative to slash
      utilization for chronic illness.
AB  - Find out why this disease management program has had such good success managing
      total health care for enrolled patients and is expanding into cardiac care,
      asthma, and COPD--while putting plenty of dollars to the bottom line.

PMID- 11345932
TI  - Capitation remains a strong factor in 'best practice' medical groups.
AB  - Data Insight: What characteristics are common to better performing medical
      groups? For one, they are more likely to have a higher percentage of capitation
      revenue. Get all the details, plus one expert's view of the reinsurance market
      and prospects for capitation in today's economic climate.

PMID- 11345933
TI  - Do you really know how risk works these days?
AB  - There's a new player in the risk contracting arena--provider-owned intermediaries
      that come between health plans and physicians. Get the details from the first
      ever study of these new entities, and their implications for at-risk providers.

PMID- 11345934
TI  - CA physicians reach agreement with Aetna while RICO suit against other plans
      grows.
AB  - California physicians have reached an agreement with Aetna but have now joined
      with physicians from two other states in refiling a federal lawsuit against
      several major for-profit plans charging civil violations of racketeering laws.

PMID- 11345935
TI  - [Use of DDT in the antimalarial program].

PMID- 11345936
TI  - [Prevention of mother-child HIV transmission: a shortened and simplified
      zidovudine treatment].

PMID- 11345938
TI  - [Chagas disease always present in the Brazilian northeast].

PMID- 11345937
TI  - [A major step has been overcome in the eradication of poliomyelitis: the Pacific
      occidental region is certified as exempt from this disease].

PMID- 11345939
TI  - [Rains threaten to aggravate the malaria epidemic in Burundi].

PMID- 11345940
TI  - Acid-base disturbance.

PMID- 11345941
TI  - Acid-base physiology.
AB  - Acid-base homeostasis involves chemical and physiologic processes responsible for
      the maintenance of the acidity of body fluids at levels that allow optimal
      function of the whole individual. The chemical processes represent the first line
      of defense to an acid or alkali load and include the extracellular and
      intracellular buffers, whereas the physiologic processes modulate acid-base
      composition by changes in cellular metabolism and by adaptive responses in the
      excretion of volatile acids by the lungs and fixed acids by the kidneys. The need
      for the existence of multiple mechanisms involved in acid-base regulation stems
      from the critical importance of the hydrogen ion (H+) concentration on the
      operation of many cellular enzymes and function of vital organs, most prominently
      the brain and the heart. The task imposed on the mechanisms that maintain acid
      base homeostasis is large, since metabolic pathways are continuously consuming or
      producing H+, and the daily load of waste products for excretion in the form of
      volatile and fixed acids is substantial. We review the determinants of the
      acidity of body fluids, the mechanisms that maintain normal acid-base
      composition, and the overall defense to disruption in acid-base equilibrium.
      Specific topics include an examination of the scales of acidity, buffer systems,
      intracellular acid-base regulation, excretion of acids, alkali and acid loading,
      and normal acid-base composition. The limitations of arterial blood sampling in
      the assessment of acid-base status are also evaluated.

PMID- 11345942
TI  - Na+/H+ exchange in ischemia, reperfusion and preconditioning.

PMID- 11345943
TI  - Overexpression of the Na/Ca exchanger and reduced SERCa function.

PMID- 11345945
TI  - A different perspective on a rotavirus vaccine.

PMID- 11345944
TI  - Clinical value of whole-body emission tomography in potentially curable 
      colorectal liver metastases.
AB  - AIMS: In selected patients with colorectal liver metastases, hepatic resection
      offers an opportunity for cure, with a 25-38% 5-year survival rate. The aim of
      this prospective study was to evaluate whether patient selection could be
      improved with pre-operative whole-body 18-fluoro-2-deoxyglucose-positron emission
      tomography (FDG-PET) scan. METHODS: Ninety-one consecutive patients were
      considered to be eligible for liver resection after investigation with
      conventional diagnostic methods (CDM). In all these patients a whole-body PET
      scan with FDG was performed prior to surgery. Follow-up was complete with a mean
      of 23 months (2 weeks-92 months). All PET images were reviewed blinded to
      intraoperative and follow-up data. RESULTS: PET confirmed liver metastases in 90
      (99%) patients, while it provided additional information in 10 (11%) patients,
      i.e., seven intra-abdominal, and three extra-abdominal. PET falsely upstaged six
      (6.6%) patients in whom malignancy was excluded by additional investigation, at
      the time of surgery, or during follow-up. PET falsely understaged seven (7.7%)
      patients with small intra-abdominal lesions. CONCLUSION: In patients with
      potentially curable colorectal liver metastases according to conventional
      diagnostic methods, whole-body FDG-PET can be considered as a complementary
      examination in order to further select patients for potentially curative liver
      resection, and to optimize therapeutic strategy.

PMID- 11345946
TI  - Frequency of sexual dysfunctions in patients with schizophrenia on haloperidol,
      clozapine or  risperidone.

PMID- 11345947
TI  - An open trial of risperidone augmentation of partial response to clozapine.

PMID- 11345948
TI  - Snoring prior to fatal opiate overdose: an intervention opportunity?

PMID- 11345949
TI  - Re: paternity and hormone levels after unilateral cryptorchidism: association
      with pretreatment testicular location.

PMID- 11345950
TI  - Re: Failure to achieve castrate levels of testosterone during luteinizing hormone
      releasing hormone agonist therapy: the case for monitoring serum testosterone and
      a treatment decision algorithm.

PMID- 11345951
TI  - Tumorigenic pathways in low-stage bladder cancer based on p53, MDM2 and p21
      phenotypes.

PMID- 11345952
TI  - Disseminated septic arthritis in a patient with common variable
      hypogammaglobulinemia.

PMID- 11345953
TI  - Object discrimination learning in aged Japanese monkeys.
AB  - The authors investigated the behavioral aging effects of Japanese macaques in 3
      object discrimination learning tasks: learning-set (LS) formation, go/no-go
      discrimination learning, and multiple discrimination reversals. Aged monkeys
      showed deteriorated performance in these tasks compared with younger controls.
      Hypothesis analysis of LS showed that aged monkeys had difficulty learning the
      lose-shift component of the hypothesis win-stay-lose-shift with respect to
      object. Deficits in go/no-go successive discrimination were clear in no-go trials
      only in the first 2 pairs of 5 tasks. Performance of aged monkeys was severely
      disturbed from a chance to criterion level in discrimination reversals. These
      results are attributed not only to increased tendency for perseveration but also
      to difficulty in associating the reward and the object in aged monkeys and may be
      related to the decline in the functions of the ventral frontal cortex.

PMID- 11345954
TI  - Neural substrates of crossmodal association memory in monkeys: the amygdala
      versus the anterior rhinal cortex.
AB  - Nine rhesus monkeys were trained on visual, tactual, and crossmodal (tactual
      visual) versions of delayed nonmatching-to-sample (DNMS). They then received
      bilateral aspiration lesions of the anterior rhinal cortex or bilateral
      excitotoxic lesions of the amygdala or were retained as unoperated controls.
      Monkeys with anterior rhinal cortex lesions displayed a persistent deficit on
      crossmodal DNMS as well as a deficit on tactual DNMS. In contrast, monkeys with
      amygdala lesions exhibited only a transient impairment on crossmodal DNMS, and
      their difficulty appeared to be related to inadvertent damage to the anterior
      rhinal cortex. The present findings support the idea that the rhinal cortex is
      important for the formation and retrieval of stimulus-stimulus associations
      across sensory modalities.

PMID- 11345955
TI  - On the behavioral significance of head direction cells: neural and behavioral
      dynamics during spatial memory tasks.
AB  - Current theories assume that rats use the directional information reflected by
      head direction (HD) cells when performing spatial tasks. This assumption was
      assessed by monitoring anterior thalamic HD cell activity and relating it to the
      subject's behavioral response on 2 spatial memory tasks that tested either
      reference memory or working memory. In both tasks, there was a significant number
      of trials where there was not a tight coupling between the preferred firing
      direction of HD cells and the direction of the behavioral response. In addition,
      it was possible to intentionally change the preferred direction of HD cells
      without affecting performance accuracy. An additional experiment showed that
      manipulations that affected internal, but not external, cues impaired performance
      on the reference memory task. These findings suggest that HD cell activity was
      not consistently guiding the subjects' behavior on these 2 spatial tasks.

PMID- 11345956
TI  - Hemispheric memories for the content and position of food caches in the domestic
      chick.
AB  - From Day 2 to Day 4 of life, chicks were fed daily in a large enclosure with 2
      identical food caches, each filled with a different type of seed. On Day 5,
      binocular and monocular chicks were fed in their home cages 1 type of seed
      exclusively for 30 min. At test, soon after this devaluation phase, both
      binocular and right-eyed chicks chose the food caches containing the seeds that
      had not been devalued; in contrast, left-eyed chicks did not show a clear choice.
      Experiments revealed that the asymmetry was not due to lack of motivation, worse
      spatial memory, or inability to remember the consequences of devaluation by left
      eyed chicks. Results suggest that young chicks can form declarative-like memories
      of the content of food caches. However, chicks using their left eye (which
      provides a supply mainly to the right hemisphere) failed to integrate memory of
      the content of food caches with memory of the consequences of devaluation.

PMID- 11345957
TI  - Contribution of the cholinergic basal forebrain to proactive interference from
      stored odor memories during associative learning in rats.
AB  - E. De Rosa and M. E. Hasselmo (2000) demonstrated that 0.25 mg/kg scopolamine
      (SCOP) selectively increased proactive interference (PI) from stored odor
      memories during learning. In the present study, rats with bilateral cholinergic
      lesions limited to the horizontal limb of the diagonal band of Broca, made with
      192 IgG-saporin, were not impaired in acquiring the same olfactory discrimination
      task relative to control rats. Rats with bilateral 192 IgG-saporin lesions to all
      basal forebrain cholinergic nuclei (BF) also showed no impairment in acquisition
      of this task. However, the BF-saporin rats were hypersensitive to oxotremorine
      induced hypothermia and demonstrated an increased sensitivity to PI following a
      low dose of SCOP (0.125 mg/kg) relative to control rats. The results suggest that
      weaker cholinergic modulation after cholinergic BF lesions makes the system more
      sensitive to PI during blockade of the remaining cholinergic elements.

PMID- 11345958
TI  - The effects of nucleus basalis magnocellularis lesions in Long-Evans hooded rats
      on two learning set formation tasks, delayed matching-to-sample learning, and
      open-field activity.
AB  - Rats with quisqualic acid lesions of the nucleus basalis magnocellularis (nBM)
      and control rats were compared in discrimination reversal learning set (DRLS) and
      olfactory discrimination learning set (ODLS) tasks, a delayed matching-to-sample
      task (DMTS), and open-field activity. Evidence of learning set formation was seen
      in control rats but not in nBM-lesioned rats in both the DRLS and ODLS tasks.
      Better-than-chance performances were seen for both groups in DMTS, indicating no
      impairment after nBM lesions. There were no group differences in open-field
      activity. These findings suggest that the nBM is important for higher cognitive
      processing such as "learning to learn" and thus is important for a complex form
      of reference memory. In addition, perseverational, working memory, and
      attentional deficits could not explain learning set impairment after nBM lesions.

PMID- 11345959
TI  - Combined hippocampal and amygdala lesions block learning of a response
      independent form of occasion setting.
AB  - This study compared rats with dorsal striatal, ventrolateral prefrontal cortical,
      and combined lesions of the hippocampus and amygdala to sham controls on a
      conditional discrimination task in which contextual cues modulated a taste
      aversion. All groups were able to acquire this occasion setting task. The 2nd
      experiment functionally minimized the stimulus-response component of the
      paradigm, creating a "tasteless" form of occasion setting. Rats with pretraining
      lesions of the hippocampus and amygdala were impaired compared with shams on the
      acquisition of this tasteless occasion setting task. Rats with posttraining
      combined lesions did not retain the ability to perform the tasteless occasion
      setting task learned preoperatively. Rats with selective lesions of either the
      hippocampus or the amygdala alone were not impaired in the acquisition of the
      tasteless occasion setting task. The findings suggest that this occasion setting
      task may be learned by several redundant neural systems.

PMID- 11345960
TI  - Human fear conditioning is related to dopaminergic and serotonergic biological
      markers.
AB  - Biological markers for acquisition and extinction of fear conditioning were
      studied in 40 individuals selected for displaying either good or poor acquisition
      of fear conditioning. as estimated by the skin conductance response. Participants
      with a short serotonin transporter (5-HTT) promoter allele or low monoamine
      oxidase activity in platelets (trbc-MAO) displayed better acquisition than those
      with only long alleles or high trbc-MAO, whereas participants with a long
      dopamine D4 receptor (D4DR) exon III allele showed delayed extinction compared
      with those with only short alleles. The findings, that D4DR exon III and 5-HTT
      promoter genotypes and trbc-MAO activity are related to human fear conditioning,
      a basic form of associative learning, are consistent with animal studies
      suggesting a genetic contribution to fear conditioning. The authors suggest that
      in humans these genetic mechanisms are partly dopaminergic and serotonergic in
      origin.

PMID- 11345961
TI  - Fear conditioning to tone, but not to context, is attenuated by lesions of the
      insular cortex and posterior extension of the intralaminar complex in rats.
AB  - C. Shi and M. Davis (1999) recently reported that combined lesions of the
      posterior extension of the intralaminar complex (PINT) and caudal insular cortex
      (INS) block acquisition but not expression of fear-potentiated startle to
      discrete conditioned stimuli (CSs) and a footshock unconditioned stimulus (US)
      and proposed that PINT-INS projections to the amygdala constitute the essential
      US pathways involved in fear conditioning. The present study further tested this
      hypothesis by examining whether PINT-INS lesions block fear conditioning (as
      measured by freezing) to diffuse-context and discrete-tone CSs, and whether
      posttraining lesions with continued CS-US training result in extinction to the
      CSs. Posttraining lesions resulted in a selective attenuation of tone
      conditioning, but context conditioning was unaffected by pre- and posttraining
      lesions. These results do not support the view that the PINT-INS represent the
      essential US pathway in fear conditioning.

PMID- 11345962
TI  - The effects of apomorphine and haloperidol on memory consolidation in the day-old
      chick.
AB  - Apomorphine was found to disrupt memory consolidation in a dose-dependent manner
      on chicks trained on a 1-trial passive avoidance task with a strong aversant
      experience. Chicks injected with 4.0 mg/kg apomorphine displayed memory deficits
      at 180 min after learning and showed marked behavioral disturbances, including
      increased locomotion and increased pecking at the feet of conspecifics.
      Pretreatment with the dopamine antagonist haloperidol eliminated the memory
      disturbance induced by apomorphine and facilitated consolidation of memory in
      chicks given a weak (20% vol/vol methyl anthralinate) training experience. Time
      of-retention data suggested that the memory disruption occurred from 120 min
      after learning, leading to the suggestion that dopamine-related modulation of the
      training experience may be involved in late-memory formation processes.

PMID- 11345963
TI  - Memory retention is modulated by acute estradiol and progesterone replacement.
AB  - Ovarian hormones alter spine density of hippocampal granule and pyramidal cells
      in young adult and aging female rats (P. Miranda, C. L. Williams, & G. Einstein,
      1999; C. S. Woolley, 1998). The present study used a delayed matching-to-place
      version of the water maze to investigate a behavioral correlate of these hormone
      induced changes in hippocampal connectivity in 3- and 8-month-old female rats.
      When primed with 10-microg injections of estradiol 72 and 48 hr before testing,
      the memory retention of ovariectomized rats was improved compared with retention
      after priming with oil. A single injection of progesterone maintained this
      enhancement if testing occurred within 8 hr of the progesterone injection but not
      if testing occurred more than 24 hr after the progesterone injection. These
      findings indicate that estradiol and progesterone alter memory retention and
      suggest that these changes may be the result of hormone-induced increases in
      hippocampal connectivity.

PMID- 11345964
TI  - Cocaine seeking by rats is a goal-directed action.
AB  - In two experiments rats were trained to self-administer intravenous cocaine on
      chained schedules using different responses in the initial (drug-seeking) and
      terminal (drug-taking) links. In both between- (Experiment 1) and within-subject
      designs (Experiment 2), the drug-taking response was then either extinguished or
      reinforced in the absence of the opportunity to perform the seeking response. In
      a subsequent extinction test with the seeking manipulanda alone, the rate of drug
      seeking was reduced after the prior extinction of the associated taking response.
      An additional group trained with a sucrose reinforcer showed a comparable
      devaluation effect. These findings demonstrate that seeking responses for cocaine
      and food rewards are mediated by a representation of the contingency between
      seeking responses and the opportunity to take the reward.

PMID- 11345965
TI  - Chronic morphine treatment exaggerates the suppressive effects of sucrose and
      cocaine, but not lithium chloride, on saccharin intake in Sprague-Dawley rats.
AB  - Three experiments examined the effect of chronic morphine treatment on cocaine-,
      sucrose-, and lithium chloride (LiCl)-induced suppression of saccharin intake in
      Sprague-Dawley rats. All rats were either water- or food-deprived and then
      implanted subcutaneously with 1 morphine (75 mg) or vehicle pellet for 5 days.
      They were then given brief access to 0.15% saccharin and soon thereafter injected
      with either cocaine (10 mg/kg s.c.), LiCl (0.009 M, 1.33 ml/100 g body weight
      i.p.), or saline, or, in Experiment 2, given a 2nd access period to either a
      preferred 1.0 M sucrose solution or the same 0.15% saccharin solution. There was
      1 taste-drug or taste-taste pairing per day for a number of days. The results
      showed that a history of chronic morphine treatment exaggerated the suppressive
      effects of a rewarding sucrose solution and cocaine but not those of the aversive
      agent, LiCl. These data provide further support for the reward comparison
      hypothesis.

PMID- 11345966
TI  - Visual attention in the rat: a role for the prelimbic cortex and thalamic nuclei?
AB  - The behavioral effects of lesions of the prelimbic cortex (PL), mediodorsal
      nucleus of the thalamus (MD), and anterior thalamic nuclei (ANT) were
      investigated in 2 attentional tasks in rats: the 5-choice serial reaction time
      task and a vigilance task. Although there was no lesion effect on accuracy in the
      5-choice task, PL lesions enhanced perseverative responding during baseline
      performance and when stimulus duration was reduced. In contrast, MD lesions
      increased premature responding during baseline performance and when the
      intertrial interval was varied unpredictably. In the vigilance paradigm, PL
      lesions also impaired rats' ability to detect the light signal at baseline and at
      the reduced stimulus duration. ANT lesions did not substantially disrupt
      performance. The results suggest that different aspects of attention may be
      attributable to the PL and the MD and that the mechanisms underlying inhibitory
      control of behavior may be attributable to functionally different thalamocortical
      circuits.

PMID- 11345967
TI  - Dimensions of emotionality in a rat model of innate anxiety.
AB  - Emotionality is thought to be multidimensional, with "anxiety" representing one
      dimension. Dissecting emotional dimensions in animal models is an essential
      prerequisite for investigating the neurobiological mechanisms that underlie
      anxiety. The authors used factor analysis to investigate emotional dimensions in
      normal rats and rats bred for either high or low anxiety-related behavior.
      Hyperanxious rats were reduced in emotional dimensions in the elevated plus-maze
      by selection pressure, and a modified hole board test revealed a dissection of
      their emotionality with precisely defined dimensions. This enabled clear
      differentiation of "anxiety" from other emotional dimensions including risk
      assessment behavior and exploration. Factors extracted by analyzing data from a
      multiple-test battery corresponded to particular test characteristics rather than
      to emotional dimensions. The approach used might help to develop specific
      treatment strategies for anxiety disorders.

PMID- 11345968
TI  - Early social deprivation disrupts attentional, but not affective, shifts in rats.
AB  - This study examined the effects of early social deprivation in rats on 2
      dissociable forms of inhibitory control of behavior that operate at 2 different
      levels of response selection: reversing the assignment of stimulus-reward
      associations within perceptual dimensions (affective shifts) and switching
      selective attention from 1 perceptual dimension to another (attentional shifts).
      Isolated subjects (isolates) and social controls (socials) were individually
      trained to spatial and nonspatial visual discrimination criteria on a radial arm
      maze. Whereas isolates and socials differed in neither acquisition nor reversal
      of both versions of the task, isolates were selectively impaired in shifting from
      spatial to nonspatial discrimination and vice versa. These findings demonstrate
      that isolation rearing selectively disrupts inhibitory control in attentional
      selection but leaves inhibitory control in affective processing intact.

PMID- 11345969
TI  - Psychogenic, neurogenic, and systemic stressor effects on plasma corticosterone
      and behavior: mouse strain-dependent outcomes.
AB  - The effects of several stressors were assessed in inbred strains of mice,
      BALB/cByJ and C57BL/6ByJ, thought to be differentially reactive to stressors.
      Behavioral reactivity was greater in BALB/cByJ mice with respect to open-field
      emergence, step-down responding, response to a predator (rat) or to fox urine
      odor. Neurogenic insults (e.g., footshock, forced swim, restraint) and a systemic
      stressor (intraperitoneal interleukin-1beta treatment) likewise provoked a
      greater rise of plasma corticosterone in the BALB/cByJ mice. Psychogenic
      stressors (e.g., novel open-field exposure, acoustic startle stimuli) also
      enhanced plasma corticosterone to a greater extent in BALB/cByJ mice, but such an
      outcome was not apparent following predator-related cues. It appears that whereas
      stressor reactivity and adrenal glucocorticoid release may be exaggerated in
      BALB/cByJ mice, such effects may be dependent on the specific characteristic of
      the stressor situation.

PMID- 11345970
TI  - Exploration, anxiety, and spatial memory in transgenic anophthalmic mice.
AB  - Contradictory results are found in the literature concerning the role of vision
      in the perception of space or in spatial navigation, in part because of the lack
      of murine models of total blindness used so far. The authors evaluated the
      spatial abilities of anophthalmic transgenic mice. These mice did not differ
      qualitatively from their wild-type littermates in general locomotor activity,
      spontaneous alternation, object exploration, or anxiety, but their level of
      exploratory activity was generally lower. In the spatial version of the water
      maze, they displayed persistent thigmotaxic behavior and showed severe spatial
      learning impairments. However, their performances improved with training,
      suggesting that they may have acquired a rough representation of the platform
      position. These results suggest that modalities other than vision enable some
      degree of spatial processing in proximal and structured spaces but that vision is
      critical for accurate spatial navigation.

PMID- 11345971
TI  - Anxiety-related behaviors in the elevated zero-maze are affected by genetic
      factors and retinal degeneration.
AB  - Anxiety levels were tested in an elevated zero-maze for 8 inbred strains of mice
      that are used widely in biomedical and behavioral research. Strain differences
      were observed for activity, latency to enter an open quadrant, open time, and
      defecation, demonstrating that genetic factors mediate anxiety in this paradigm.
      Three of the strains have the rdl mutation that causes retinal degeneration and
      were less anxious in the maze. To discern whether visual acuity is a source of
      difference on the maze, anxiety levels were tested in a congenic strain in which
      the rdl allele has been replaced with the wild-type allele. The congenic strain,
      with normal vision, had higher levels of anxiety. This study provides baseline
      data for the selection and use of any of these strains in pharmacological
      challenges in the maze, and provides a starting point for the identification of
      strains that may have appropriate backgrounds for targeted mutation studies.

PMID- 11345972
TI  - Startle amplitude and fear in an acoustic startle paradigm: lesions to the
      brachium of the inferior colliculus or the lateral tegmental tract.
AB  - In 2 experiments, startle amplitude and startle stimulus-induced freezing (an
      index of fear) were measured in an acoustic startle response (ASR) paradigm in
      rats. Lesions to lateral tegmental tract (LTG), a pathway medial to brachium of
      the inferior colliculus (BIC), significantly decreased freezing and produced a
      persistent 5-fold increase in ASR amplitude compared with sham-operated controls.
      Lesions to BIC increased both ASR amplitude (2-fold) and freezing. Neither BIC
      nor LTG lesions affected startle amplitude when startle was elicited by a brief
      footshock stimulus. Characteristics of the lesion effects were tested with
      manipulations of interstimulus interval, stimulus intensity, and prepulse
      inhibition. The data suggest (a) an ascending pathway medial to BIC that carries
      the fear-inducing dimensions of an acoustic stimulus and (b) a descending pathway
      that provides tonic inhibition of the sensory input to the ASR circuitry.

PMID- 11345973
TI  - Hunger selectively modulates corticolimbic activation to food stimuli in humans.
AB  - Functional magnetic resonance imaging (fMRI) was used to determine whether visual
      responses to food in the human amygdala and related corticolimbic structures
      would be selectively altered by changes in states of hunger. Participants viewed
      images of motivationally relevant (food) and motivationally irrelevant (tool)
      objects while undergoing fMRI in alternately hungry and satiated conditions. Food
      related visual stimuli elicited greater responses in the amygdala,
      parahippocampal gyrus. and anterior fusiform gyrus when participants were in a
      hungry state relative to a satiated state. The state-dependent activation of
      these brain structures did not generalize to the motivationally irrelevant
      objects. These results support the hypothesis that the amygdala and associated
      inferotemporal regions are involved in the integration of subjective
      interoceptive states with relevant sensory cues processed along the ventral
      visual stream.

PMID- 11345974
TI  - American Academy of Pediatrics. Committee on Substance Abuse. Tobacco, alcohol,
      and other drugs: the role of the pediatrician in prevention and management of
      substance abuse.
AB  - During the past three decades the responsibility of pediatricians to their
      patients and their patients' families regarding the prevention of substance abuse
      and the diagnosis and management of problems related to substance abuse has
      increased. The American Academy of Pediatrics (AAP) has highlighted the
      importance of such issues in a variety of ways, including its guidelines for
      preventive services. Nonetheless, many pediatricians remain reluctant to address
      this issue. The harmful consequences of tobacco, alcohol, and other drug use are
      a concern of medical professionals who care for infants, children, adolescents,
      and young adults. Thus, pediatricians should include discussion of substance
      abuse as a part of routine health care, starting with the prenatal visit and as a
      part of ongoing anticipatory guidance. Knowledge of the extent and nature of the
      consequences of tobacco, alcohol, and other drug use as well as the physical,
      psychological, and social consequences is important for pediatricians.
      Pediatricians should incorporate substance abuse prevention into daily practice,
      acquire the skills necessary to identify young people at risk for substance
      abuse, and provide or obtain assessment, intervention, and treatment as
      necessary.

PMID- 11345975
TI  - American Academy of Pediatrics. Committee on Infectious Diseases. Age for routine
      administration of the second dose of measles-mumps-rubella vaccine.
AB  - The purpose of this statement is to inform physicians of a modification in the
      recommendation of the appropriate age for routine administration of the second
      dose of measles-mumps-rubella (MMR) vaccine. The implementation of the two-dose
      measles vaccine schedule has improved the control of measles, but some outbreaks
      continue to occur in school children, although >/= to 95% of children in school
      have received one dose of vaccine. Because most measles vaccine failures are
      attributable to failure to respond to the first dose, that all children receive
      two doses of measles-containing vaccine is essential for the control of measles.
      Routine administration of the second dose of MMR vaccine at school entry (4 to 6
      years of age) will help prevent school-based outbreaks. Physicians should
      continue to review the records of all children 11 to 12 years of age to be
      certain that they have received two doses of MMR vaccine after their first
      birthday. Documenting that all school children have received two doses of measles
      containing vaccine by the year 2001 will help ensure the elimination of measles
      in the United States and contribute to the global effort to control and possible
      eradicate measles.

PMID- 11345976
TI  - American Academy of Pediatrics. Committee on Child Abuse and Neglect. Gonorrhea
      in prepubertal children.
AB  - This statement updates a 1983 statement on this topic and reminds physicians that
      sexual abuse should be strongly considered when a gonorrheal infection is
      diagnosed in a child after the newborn period and before the onset of puberty.

PMID- 11345977
TI  - American Academy of Pediatrics. Committee on Infectious Diseases. Severe invasive
      group A streptococcal infections: a subject review.
AB  - The course of severe invasive group A beta-hemolytic streptococcal (GABHS)
      infections is often precipitous, requiring prompt diagnosis and rapid initiation
      of appropriate therapy. Therefore, physicians must have a high index of suspicion
      of this disease, particularly in patients at increased risk (e.g., those with
      varicella or diabetes mellitus). Although a relationship between the use of
      nonsteroidal antiinflammatory drugs and severe invasive GABHS infections has been
      suggested, at present data on which to base a clinical decision about the use or
      restriction of nonsteroidal antiinflammatory drugs in children with varicella are
      insufficient. When necrotizing fasciitis is suspected, prompt surgical drainage,
      debridement, fasciotomy, or amputation often is necessary. Many experts recommend
      intravenously administered penicillin G and clindamycin for the treatment of
      invasive GABHS infections on the basis of animal studies. Some evidence exists
      that intravenous immunoglobulin given in addition to appropriate antimicrobial
      and surgical therapy may be beneficial. Although chemoprophylaxis for household
      contacts of persons with invasive GABHS infections has been considered by some
      experts, the limited available data indicate that the risk of secondary cases is
      low (2.9 per 1000) and data about the effectiveness of any drug are insufficient
      to make recommendations. Because of the low risk of secondary cases of invasive
      GABHS infections in schools or child care facilities, chemoprophylaxis is not
      indicated in these settings. Routine immunization of all healthy children against
      varicella is recommended and is an effective means to decrease the risk of
      invasive GABHS infections.

PMID- 11345978
TI  - American Academy of Pediatrics. Committee on Nutrition. Cholesterol in childhood.
AB  - This updated statement reviews the scientific justification for the
      recommendations of dietary changes in all healthy children (a population
      approach) and a strategy to identify and treat children who are at highest risk
      for the development of accelerated atherosclerosis in early adult life (an
      individualized approach). Although the precise fraction of risk for future
      coronary heart disease conveyed by elevated cholesterol levels in childhood is
      unknown, clear epidemiologic and experimental evidence indicates tha the risk is
      significant. Diet changes that lower fat, saturated fat, and cholesterol intake
      in children and adolescents can be applied safely and acceptably, resulting in
      improved plasma lipid profiles that, if carried into adult life have the
      potential to reduce atherosclerotic vascular disease.

PMID- 11345979
TI  - American Academy of Pediatrics. Committee on Nutrition. Soy protein-based
      formulas: recommendations for use in infant feeding.
AB  - The American Academy of Pediatrics is committed to the use of maternal breast
      milk as the ideal source of nutrition for infant feeding. Even so, by 2 months of
      age, most infants in North America are formula-fed. Despite limited indications,
      the use of soy protein-based formula has nearly doubled during the past decade to
      achieve 25% of the market in the United States. Because an infant formula
      provides the largest, if not sole, source of nutrition for an extended interval,
      the nutritional adequacy of the formula must be confirmed and the indications for
      its use well understood. This statement updates the 1983 Committee on Nutrition
      review and contains some important recommendations on the appropriate use of soy
      protein-based formulas.

PMID- 11345980
TI  - American Academy of Pediatrics. Committee on Infectious Diseases. Recommended
      childhood immunization schedule--United States, January-December 1998.

PMID- 11345981
TI  - CDC/AAP/Group B streptococcal infections.

PMID- 11345982
TI  - Kernicteric findings at autopsy in two sick near term infants.

PMID- 11345983
TI  - Tubefeeding.

PMID- 11345984
TI  - Outcome of children after near drowning.

PMID- 11345985
TI  - Why we really do need Ritalin.

PMID- 11345986
TI  - Scrapie: improving notification.

PMID- 11345987
TI  - Foot-and mouth disease: the government moves towards limited vaccination.

PMID- 11345988
TI  - When should bitches be neutered.

PMID- 11345989
TI  - Vaccination and fibrosarcomas in cats.

PMID- 11345991
TI  - Ultrasonographic appearance of the superficial supramammary lymph nodes in
      lactating dairy cattle.
AB  - The superficial supramammary lymph nodes of 54 lactating dairy cows were examined
      ultrasonographically with a 7.5 MHz linear transducer; each node was measured in
      two planes within 24 hours of recording the milk somatic cell count. In most
      cows, the nodes were well demarcated from the surrounding tissue. The parenchyma
      of the nodes ranged from hypoechoic to anechoic, with a central bright
      hyperechoic area, and a thin hyperechoic line surrounded the nodes. The size of
      the nodes varied, but their internal architecture remained relatively consistent.
      Their mean length was 7.4 cm (range 3.5 to 15 cm) and their mean depth was 2.5 cm
      (range 1.2 to 5.7 cm). They were significantly larger in cows with more
      lactations (P<0.05), but there were no correlations between their size and either
      the time calved or the milk somatic cell count. The lymph nodes on sides which
      were positive in a California milk test were significantly larger than those on
      sides which were negative (P<0.05).

PMID- 11345992
TI  - Relationships between the shedding of Coxiella burnetii, clinical signs and
      serological responses of 34 sheep.
AB  - Two abortions associated with Coxiella burnetii occurred in a group of 34
      pregnant ewes. The seroprevalence of C. burnetii infection was studied by using
      an ELISA and the immunofluorescence (IF) assay was applied to the contents of
      vaginal swabs. In addition, a PCR assay, with primers based on a transposon-like
      repetitive region of the C. burnetii genome (trans-PcR), was used for the highly
      sensitive and specific detection of C. burnetii in vaginal swabs, milk and
      faeces. Of the 34 animals tested at parturition, eight (24 per cent) were
      positive by ELISA, 11 (32 per cent) were positive by IF, and 15 (44 per cent)
      were positive when the vaginal swab extract was subjected to the trans-PCR assay.
      C. burnetii was therefore detected by PCR in the vaginal swabs of seven
      seronegative ewes. However, five weeks after lambing, 16 (47 per cent) of the
      animals tested were ELISA positive but only two animals (6 per cent) were
      positive by PCR. Among the ELISA- and PCR-positive animals, eight (25 per cent)
      shed coxiella in their milk and six (18 per cent) did so in their faeces.

PMID- 11345993
TI  - Use of a bioabsorbable implant for the repair of severed digital flexor tendons
      in four horses.
AB  - A new bioabsorbable implant composed of poly-L-lactic acid was used to repair the
      severed digital flexor tendons of four horses. The limbs were immobilised with
      distal casts which were changed after six to eight weeks and removed after 12 to
      16 weeks. The horses were followed clinically and ultrasonographically for from
      seven to 19 months after the surgery. The ultrasonographic examination after the
      cast had been removed showed that the implants had been well incorporated into
      scar tissue. Two of the horses were mildly lame at the trot seven months after
      the surgery, but had returned to work after 12 months. The other two horses are
      still lame. No complications were observed with the implant.

PMID- 11345994
TI  - Activity of toltrazuril and diclazuril against Isospora species in kittens and
      puppies.

PMID- 11345995
TI  - Review of canine rabies prevalence under two different vaccination programmes in
      Korea.

PMID- 11345996
TI  - Perineomelia, polydactyly and other malformations in a Mashona calf.

PMID- 11345997
TI  - Livestock welfare disposal scheme: reappraisal of outstanding applications.

PMID- 11345998
TI  - FMD control strategies.

PMID- 11345999
TI  - FMD control strategies.

PMID- 11346001
TI  - FMD control strategies.

PMID- 11346000
TI  - FMD control strategies.

PMID- 11346002
TI  - FMD control strategies.

PMID- 11346004
TI  - Chemical castration of cockerels.

PMID- 11346005
TI  - Protection to +12 Gz.
AB  - BACKGROUND: The U.S. Air Force has developed +Gz-protective equipment that will
      provide most pilots protection to +9 Gz with minimal-to-no straining. This
      equipment includes a pressure breathing system called COMBAT EDGE (CE), which is
      currently operational, and the Advanced Technology Anti-G Suit (ATAGS), which is
      not yet operational. For future high-performance aircraft design it is important
      to know the upper limit of various protective equipment and techniques. METHODS:
      Six subjects were randomly exposed to a 12-cell matrix composed of +Gz and the
      following combinations of protective equipment at three seat-back angles (13
      degrees, 30 degrees and 55 degrees from the vertical): 1) the standard CSU-13B/P
      anti-G suit (STD); 2) the STD suit with CE; 3) the ATAGS; and 4) the ATAGS with
      CE. Relaxed, followed by straining +Gz tolerance was determined using 15-s rapid
      onset runs to a maximum of +12 Gz. A comprehensive battery of baseline and post
      exposure medical surveillance studies was performed to evaluate the medical
      consequences of these high +Gz exposures. RESULTS: All 6 subjects were able to
      achieve +12 Gz with various combinations of +Gz-protective equipment, seat-back
      angle, and various amounts of straining, from none to maximum. When the data were
      collapsed over all protective equipment there was a significant (p < 0.05) seat
      effect. Relaxed tolerance to ROR increased with seat-back angle from 13 degrees
      to 30 degrees to 55 degrees. There was also a significant protective equipment
      effect when the data were collapsed over all seat-back angles. CONCLUSIONS: These
      data confirm that effortless protection to +9 Gz is available using ATAGS/CE with
      the 13 degree and 30 degree seat-back angle (F-15, F-16 and F-22) and to +10.5 Gz
      with a 55 degree seat-back angle. Moreover, with ATAGS/CE, and a moderate degree
      of straining, +12 Gz is definitely achievable at 55 degrees, even with reduced
      anti-G suit pressure at 55 degrees. With additional straining +12 GC is also
      achievable at the 13 degree and 30 degree seat-back angles.

PMID- 11346006
TI  - Effect of repeated +Gz exposures on energy metabolism and some ion contents in
      brain tissues of rats.
AB  - BACKGROUND: It has been demonstrated that during +Gz exposure cerebral blood flow
      is significantly reduced, resulting in brain ischemia. In pilots, such conditions
      could recur several times during centrifuge training and combat maneuvers and
      could possibly cause reversible change in brain energy metabolism. HYPOTHESIS: In
      rats there is an association between +10 Gz exposure and the decreased brain
      metabolism, as indicated by decreased adenosine triphosphate (ATP) and ATPase
      activity, and increased adenosine diphosphate (ADP) and lactate, etc. The aim of
      the present study was to examine the time course and recovery of brain energy
      metabolism, lactate, ATPase activity, Na+, K+, Ca2+ and water contents after
      three +10 Gz exposures in rats. METHODS: There were 64 male Sprague-Dawley rats
      that were restrained and placed on an animal centrifuge. They were divided into
      groups of 16. Control rats were exposed to +1 Gz and experimental rats were
      exposed to +10 Gz three times each for 3 min at 30-min intervals. After being
      euthanized, rat brains were removed 0 h, 1 h, or 6 h after the last centrifuge
      run. Brain samples were analyzed for energy metabolism, lactate, Na+-K+-ATPase
      activity, water and electrolytes contents. RESULTS: The cortical ATP content, Na+
      K+-ATPase and lactate dehydrogenase (LDH) activities decreased significantly,
      whereas the cortical ADP, adenosine monophosphate (AMP) and lactate contents
      increased significantly 0 h after three +10 Gz exposures, as compared with those
      of control. The ATP, ADP, and AMP contents returned to their control levels 1 h
      after the +10 Gz exposures, however, lactate content, Na+-K+-ATPase and LDH
      activities delayed recovery 6 h after +10 Gz exposures. The cortical K+ content
      increased significantly 0 h and 1 h after +10 Gz exposures, and returned to the
      control level 6 h after +Gz exposures. Na+ and water contents increased
      significantly 1 h and 6 h after the +10 Gz exposures. There was no significant
      change in Ca2+ content after +Gz exposures. CONCLUSIONS: Three +10 Gz (3 min
      each) exposures were associated with transient depression of brain metabolism as
      indicated by a decrease in ATP, Na+-K+-ATPase activity, and an accumulation of
      lactate, and disturbance of ion homeostasis. It is suggested that a causal
      relationship might exist between repeated high +Gz exposures and brain
      metabolism.

PMID- 11346007
TI  - Relationship between arm pain and distension of arteries and veins caused by
      elevation of transmural pressure in local vascular segments.
AB  - BACKGROUND: Exposure to high +Gz forces may induce arm pain, which has been
      hypothesized to be caused by pressure-induced overdistension of local blood
      vessels. The purpose of the present investigation was to study the pressure
      distension relation of veins and arteries in the human arm and the relation
      between arm pain and distension of local vessels. METHODS: Increased distending
      pressures (DP) in the vasculature of the arm were accomplished by placing the
      subject (n = 8) in a pressure chamber with one arm positioned through a port in
      the chamber door, and increasing chamber pressure to +180 mm Hg in a stepwise
      manner. Diameters in the brachial artery and in the brachial, radial and cephalic
      veins were measured by ultrasonography. Changes in forearm volume were estimated
      from measurement of tissue impedance. Perceived pain was rated using a 10-point
      scale. RESULTS: Arm pain increased with pressure to a maximum rating of 8.5 (=
      median; range: 4-10). Increasing DP from 30 to 180 mm Hg resulted in a steady
      increase (p < 0.05) in venous diameter which varied from 12 +/- 8% (mean +/- SD)
      in the brachial vein to 23 +/- 14% in the radial vein. Inthe brachial vein
      diameter increases were most pronounced at the sites of the venous valves.
      Arterial diameter was unchanged up to a DP of about 200 mm Hg (calculated as
      diastolic arterial pressure + applied chamber pressure), but then increased by 32
      +/- 9% (p < 0.001). Forearm impedance dropped with increasing pressure (delta =
      23 +/- 5%; p < 0.01); the rate of change was non-linear with a faster change at
      the highest DP which may indicate pressure distension of precapillary resistance
      vessels. CONCLUSIONS: Elevation of pressure in arm vessels to levels that may
      occur in pilots flying high-performance aircraft results in distension not only
      of veins but also of arteries and probably of smaller precapillary vessels.
      Therefore, and because these changes coincide with the development of severe arm
      pain, local overdistension of blood vessels remains a plausible cause of G
      induced arm pain.

PMID- 11346008
TI  - The "Airmedical F.A.S.T." for trauma patients--the initial report of a novel
      application for sonography.
AB  - BACKGROUND: While established as an initial screening tool for the evaluation of
      injured patients at the trauma center, sonographic evaluation of the patient in
      the prehospital setting remains untested. The purpose of this study was to
      determine the feasibility of this procedure during prehospital helicopter
      transport. METHODS: Two qualified flight surgeons performed all imaging studies.
      Confirmatory endpoints were documented for all images obtained in flight.
      RESULTS: For this preliminary study, 100 patients are presented; 84 studies were
      analyzed; 16 were excluded due to patient weight (8), hemodynamic instability
      (6), or problems with machine calibration (2). Sensitivity was 81.3%; specificity
      was 100%. The positive predictive value was 100%; the negative predictive value
      was 95.7%. The accuracy was 96.4%. CONCLUSION: Sonographic studies obtained
      during air-medical transport are of similar quality and consistency as those
      obtained in the emergency department. The ability to detect hemoperitoneum in the
      field may challenge traditional algorithms for prehospital care as a result.

PMID- 11346009
TI  - Aircraft control forces and EMG activity: comparison of pilots before and after
      flying training.
AB  - BACKGROUND: Skilled performers in most motor tasks tend to require less force,
      muscle activity, and co-contraction of agonist and antagonist muscles to complete
      tasks. There have been two previous studies on muscle activation patterns and
      applied forces of skilled and novice pilots, but no longitudinal measurements
      have been made. The aim of this study was to compare the muscle activation
      patterns of pilots who had recently completed pilot training with those of
      experienced pilots. A secondary aim of the study was to examine co-contraction of
      novice and experienced pilots. METHODS: Novice (n = 12) and experienced (n = 9)
      pilots were tested on an Aermacchi flight simulator. The novice pilots were
      tested before and after completing pilot training. Pilots performed a set of
      landings, rolls, and turns, which were administered in a random order. Variables
      recorded included aircraft attitude, pilot applied forces, and electromyographic
      (EMG) activity. Discriminant function analysis was used to classify pilots as
      novice or experienced. RESULTS: Muscle activation patterns of the novice pilots
      after completion of pilot training were similar to those of experienced pilots.
      Of the recently graduated pilots, 77% were classified as experienced using
      discriminant function analysis. The maneuver in which the recently graduated
      pilots most closely resembled experienced pilots was the left aileron roll.
      During this maneuver, experienced and recently graduated pilots showed lower
      levels of co-contraction than novice pilots (p < 0.05). CONCLUSION: The
      similarities in some muscle activity patterns across qualified pilots, regardless
      of experience level, may be useful in initiating protective systems such as G
      suit inflation.

PMID- 11346010
TI  - Cervical spine degeneration in fighter pilots and controls: a 5-yr follow-up
      study.
AB  - At 5 yr after MRI of the cervical spine, for evaluation concerning degenerative
      lesions, follow-up MRI was performed on asymptomatic experienced military high
      performance aircraft pilots (mean age 47 yr; mean accumulated flying time 3,100
      h) and on age-matched controls without military flying experience. Young military
      high performance aircraft pilots (mean age 28 yr, mean accumulated flying time
      915 h) were also re-examined. Compared with baseline MRI 5 yr earlier, there was
      significant increase in disk protrusions in all groups, in osteophytes in
      controls, and in foraminal stenoses in experienced pilots, and a significant
      reduction in disk signal intensity in young pilots. The difference between
      experienced pilots and controls was markedly reduced compared with that at
      baseline MRI. Thus, military high performance aircraft pilots seem to be at
      increased risk of premature development of degenerative lesions of the same type
      as are seen in an aging population. With increasing age the difference between
      pilots and controls diminishes.

PMID- 11346011
TI  - Characteristics of general aviation crashes involving mature male and female
      pilots.
AB  - BACKGROUND: General aviation crashes in the United States were analyzed to
      identify differences between male and female pilots in the circumstances of their
      crashes and the types of pilot errors involved. METHODS: All 144 female pilots
      who were born between 1933 and 1942 and who were involved in general aviation
      crashes between 1983 and 1997 were matched 1:2 with 287 male pilots by age within
      2 yr, medical certificate and pilot certificate, state or region of crash, and
      year of crash. RESULTS: Mechanical failure, gear up landings, improper IFR
      approaches, and collisions with wires or poles were more common in crashes of
      male pilots. Loss of control on landing/takeoff was more common in crashes of
      female pilots. Mishandling aircraft kinetics was the most common error of pilots
      of both genders and was noted more often in female pilots' crashes (81% vs. 48%)
      (p < 0.001). Males' crashes were more likely to involve flawed decisions (29% vs.
      19% of females' crashes) (p = 0.027) or inattention (32% vs. 19%) (p = 0.004).
      Older pilots made fewer errors: among males age 55-63, 26% of crashes were
      without obvious pilot error compared with only 7% at age 40-49 (p = 0.003).
      CONCLUSION: There are large gender differences in the types of pilot error
      involved in general aviation crashes. Mishandling aircraft kinetics, poor
      decision making, and inattention are the most common pilot errors and merit
      increased attention in pilot training.

PMID- 11346012
TI  - Crewmember and ground personnel interactions over time during Shuttle/Mir space
      missions.
AB  - BACKGROUND: Anecdotal reports from space and results from simulation studies on
      Earth have suggested that space crewmembers may experience decrements in their
      mood and interpersonal environment during the 2nd half of the mission and that
      negative emotions may be displaced to outside monitoring personnel. METHODS: To
      evaluate these issues, we studied 5 American astronauts, 8 Russian cosmonauts,
      and 42 American and 16 Russian mission control personnel who participated in the
      Shuttle/Mir space program. Subjects completed questions from the Profile of Mood
      States, the Group Environment Scale (GES), and the Work Environment Scale (WES)
      on a weekly basis during the missions. Subscale scores from these measures were
      analyzed using a piecewise linear regression approach that analyzed normally
      distributed subscales using a mixed model and non-normally distributed subscales
      by dichotomizing the variables and using a generalized estimating equation.
      RESULTS: After protecting against possible Type I errors due to multiple
      significance tests, only weak support was found for the biphasic model: the only
      significant findings in favor of the hypothesized 2nd half decrements in the
      interpersonal environment were in crewmember GES Leader Support and astronaut WES
      Work Pressure. Strongly consistent confirmation was found on all six tested
      measures for the hypothesized displacement of tension and dysphoria from
      crewmembers to mission control personnel. The hypothesized displacement of
      tension and dysphoria from mission control personnel to management was found on
      five of the six tested measures. CONCLUSIONS: The absence of moderate to strong
      support for the biphasic model suggests that crewmember interpersonal functioning
      does not depend appreciably on 1st half/2nd half time effects. The consistent
      support found for the displacement of tension and dysphoria suggests that
      countermeasures need to be developed to deal with this phenomenon in both
      crewmembers and mission control personnel.

PMID- 11346013
TI  - Transient and maintained changes of the spontaneous occipital EEG during acute
      systemic hypoxia.
AB  - BACKGROUND: It has been reported that during systemic hypoxia the spectral power
      of spontaneous EEG (closed eyes) increases, except for the power in the alpha
      band, which decreases. HYPOTHESIS: It is surmised that after a sudden decrease in
      inspired oxygen, the EEG parameters and SaO2 show similar temporal
      characteristics. METHODS: Normobaric acute hypoxia in 14 healthy subjects was
      evoked by breathing a hypoxic gas. Frequency spectra were calculated from
      occipital recordings and quantified together with the parameters of the spectral
      alpha peak. RESULTS: During the first 20 min of exposure, SaO2 decreases
      exponentially. With eyes open, the frequency bands show a transient increase in
      power (110-160%). The peak-time of the transient is shorter for the alpha and
      beta1 bands (4.5 min) than for the delta2 and theta bands (7 min). After the
      transient, the bands reach sustained power levels ca. 65% higher than the control
      value. The frequency of the alpha peak decreases with 0.61 +/- 0.16 Hz (mean +/-
      SE). In contrast to the eyes-closed condition, the peak amplitude increases (41
      +/- 12%). CONCLUSIONS: During systemic hypoxia many characteristics of the
      spontaneous EEG with open eyes differ from those under normoxia, and alpha
      activity deviates strongly from that during hypoxia with closed eyes. During the
      first 20 min of exposure changes in power are most prominent and do not follow
      the change of SaO2. Monitoring total EEG power with open eyes, SaO2 and
      respiration gives a good impression of the hypoxia-related neurophysiological
      state of the subject.

PMID- 11346014
TI  - Time course changes in [Ca2+]i, force, and protein content in hindlimb-suspended
      mouse soleus muscles.
AB  - BACKGROUND: Exposure to reduced gravitational forces during spaceflight is
      associated with significant reductions in skeletal muscle mass and strength. The
      purpose of this study was to test the hypothesis that increases in resting
      cytosolic free calcium concentration ([Ca2+]i) would precede reductions in
      protein content and maximal isometric tetanic force (Po) in mouse soleus muscle
      after initiation of hindlimb suspension. METHODS: Female ICR mice (n = 42) were
      hindlimb suspended for 1, 2, 3, 5, or 7 d; weight-matched mice were used as
      controls. Following the hindlimb suspension, the left soleus muscle was used to
      determine Po in vitro and the right soleus muscle was used to determine protein
      content and [Ca2+]i via confocal laser scanning microscopy. RESULTS: Compared
      with controls, [Ca2+]i was elevated by 38% at 2 d, and 117% at 7 d. Compared with
      controls, soleus muscle total and myofibrillar protein contents were reduced 27
      29% and 30-34%, respectively, at 5-7 d after initiation of hindlimb suspension.
      Compared with controls, soleus muscle Po was decreased by 24% at 3 d, and 38% at
      7 d. CONCLUSION: It appears that resting cytosolic Ca2+ homeostasis is disturbed
      soon after the initiation of hindlimb suspension, and these elevations in [Ca2+]i
      may play a role in initiating soleus muscle atrophy.

PMID- 11346015
TI  - Effect of ambient temperature on the risk of decompression sickness in surface
      decompression divers.
AB  - BACKGROUND: Several studies have noted an apparent increase in decompression
      sickness (DCS) risk with surface decompression diving in warm water or with hot
      water suits (Van Der Aue 1951, Shields 1986, Leffler 1997), but did not perform
      statistical tests to control for the pressure-time profile. METHODS: The 1986
      data, including 73 DCS cases out of 14,891 dives, were analyzed by Mantel
      Haenszel analysis to control for depth and bottom time. Dive profiles from the
      1951 U.S. Navy report, including 147 DCS cases from 1507 dives, were analyzed
      with logistic regression analysis to control for depth, bottom time, and aspects
      of the decompression profile. RESULTS: In the 1986 data, hot water suits, as
      compared with passive thermal protection, were associated with an odds ratio (OR)
      of 1.81 (95% confidence interval, CI = 0.96 to 3.42) for DCS. In the 1951 data,
      each 10 degree C increase in water temperature yielded an OR for DCS of 1.96 (95%
      CI = 1.33 to 2.90). The interaction of temperature and bottom time suggested that
      the effect was more pronounced in shorter dives. Among DCS cases, the OR for type
      2 symptoms with hot water suits was not significant in the 1986 data (p = 0.18).
      In the 1951 data, the probability of type 2 symptoms among DCS cases was better
      explained by the dive profile than by the temperature. Thermal effects on gas
      physics, metabolism, hemostasis, and nociception were reviewed. CONCLUSION:
      Surface decompression divers who are warm at depth face an increased risk of DCS.
      Vasodilatation in warm divers may result in more rapid on-gassing of tissues with
      short time constants. A full evaluation of DCS risk should consider physiological
      and physical effects of ambient temperature.

PMID- 11346016
TI  - Simulated shuttle egress: role of helmet visor position during approach and
      landing.
AB  - BACKGROUND: We previously reported that carbon dioxide (CO2) rapidly accumulates
      in the helmet of the NASA Launch and Entry Suit (LES) during a simulated egress
      from the Space Shuttle following 6 min of visor-closed seated rest to simulate
      approach and landing. The purpose of this study was to determine if CO2
      accumulation and walking time in the LES would be improved by helmet visor-open
      rather than visor-closed seated rest prior to the performance of the simulated
      egress. METHODS: Wearing the LES, 12 male subjects performed 4 laboratory egress
      simulations consisting of 6-min seated rest, 2-min stand, and 5-min walk at 1.56
      m x s(-1) (3.5 mph). During seated rest, subjects sat either with the visor open,
      breathing room air until the visor was closed on standing, or with the visor
      closed for the duration of the simulation. For all visor-closed operations 100%,
      O2 was supplied. The G-suit was either deflated (0.0 psi) or inflated to 1.5 psi.
      Inspired CO2 and walking time were measured. Data were analyzed at the end of
      seated rest, standing, and after 5 min of walking at 0.0 psi or after 2 min of
      walking at 1.5 psi (>90% of data available). RESULTS: Walk time was not different
      following visor-open (0.0 psi: 5.0 +/- 0.0; 1.5 psi: 3.4 +/- 0.3 min) or visor
      closed (0.0 psi: 4.8 +/- 0.2; 1.5 psi: 3.5 +/- 0.4 min) seated rest at either G
      suit pressure. Inspired CO2 levels were not different between the two conditions
      during walking at 5 min at 0.0 psi (p = 0.50; Open: 4.39 +/- 0.14; Closed: 4.48
      +/- 0.18%) or at 2 min at 1.5 psi (p = 0.53; Open: 3.59 +/- 0.12; Closed: 3.65 +
      0.21%). CONCLUSIONS: Visor position during seated rest immediately preceding the
      egress walk had no effect on inspired CO2 or walking time.

PMID- 11346017
TI  - Case from the aerospace medicine residents' teaching file. Stingray injury.
AB  - A case report is presented of an aviator with a stingray injury. The complicated
      diagnosis, treatment, delayed healing, and aeromedical disposition of this injury
      are discussed.

PMID- 11346018
TI  - Nanomachines and aerospace medicine.

PMID- 11346019
TI  - School of Aviation Safety fights civilian airline accidents.

PMID- 11346020
TI  - Cell transplantation for the treatment of Parkinson's disease.
AB  - Cell transplantation is an experimental therapy for Parkinson's disease (PD) and
      other movement disorders. Several open-label research trials have shown
      clinically meaningful improvement in parkinsonian signs and symptoms after
      striatal transplantation of allogeneic fetal ventral mesencephalic (FVM) tissue.
      However, ethical concerns, variability in surgical techniques, and reports of
      unusual late complications in a few patients in a clinical trial have limited the
      use of allogeneic FVM tissue to a few research centers. Research into alternative
      cell sources such as porcine FVM and allogeneic retinal pigment epithelial cells
      has shown promising results in preclinical trials, and they are currently being
      tested in clinical trials. Novel strategies to improve cell survival and to avoid
      immune rejection of transplants show promising results in preclinical trials.
      This article focuses on these recent advances and compares the potential clinical
      utility of these emerging cell therapies for the treatment of advanced PD.

PMID- 11346021
TI  - Catechol-O-methyltransferase inhibitors in the management of Parkinson's disease.
AB  - Parkinson's disease is the most common neurodegenerative disease in which the
      chemical pathology is known and effective symptomatic treatment, levodopa, is
      available. Therapy in the initial years after initiation with dopa decarboxylase
      inhibitors, carbidopa or benserazide, combined with levodopa results in
      favorable, stable responses. However, by 5 years after the initiation of
      treatment, over two thirds of patients experience motor fluctuations beginning
      initially with a "wearing-off" effect followed by more complex fluctuations
      including dyskinesias and "on-off" responses. A number of strategies have been
      developed in an attempt to deal with these complications including changing doses
      and frequencies, adding agonist medications, adding or substituting controlled
      release levodopa, and surgical therapies. A more recent strategy has centered on
      increasing the availability of intracellular levodopa and synaptic dopamine by
      inhibiting the peripheral and central metabolism of levodopa to 3-O-methyldopa
      with the use of a catechol-O-methyltransferase inhibitor. To date, two of these
      inhibitors, tolcapone and entacapone, are available to treat the wearing-off
      phase of levodopa therapy.

PMID- 11346022
TI  - Functional imaging in Parkinson's disease.
AB  - This article reviews the applications of functional neuroimaging with positron
      emission tomography (PET) and single photon emission computed tomography (SPECT)
      to the diagnosis and treatment of Parkinson's disease (PD). PET measurements with
      [18F]deoxyglucose to measure glucose metabolism or with various markers of the
      pre- and postsynaptic dopamine systems may distinguish idiopathic PD from other
      conditions presenting with an akinetic-rigid state. Moreover, PET has been used
      to gain new insights into mechanisms of cell death and the role of heredity in
      Parkinson's disease. Finally, we discuss the use of functional neuroimaging to
      study the role of the basal ganglia in movement and cognition in PD.

PMID- 11346023
TI  - Multiple system atrophy.
AB  - Multiple system atrophy (MSA) is an adult-onset sporadic progressive
      neurodegenerative disorder of unknown etiology. It is clinically characterized by
      the variable combination of autonomic failure, parkinsonism, cerebellar ataxia,
      and pyramidal signs. The present review summarizes up-to-date knowledge on the
      clinical diagnosis and molecular pathology of MSA. We also review the role of
      additional investigations that may support a clinical diagnosis of MSA. Finally,
      we briefly discuss the management of MSA, focusing on possible future therapeutic
      strategies.

PMID- 11346024
TI  - Diagnosis and management of progressive supranuclear palsy.
AB  - Because of the relevance of an early and accurate diagnosis for prognosis,
      management, and participation of patients in research, the classical clinical
      features--features that should raise suspicion of progressive supranuclear palsy
      (PSP) and those that should make the diagnosis of PSP unlikely--are discussed in
      this article. The accuracy of currently used clinical diagnostic criteria and the
      role of laboratory investigations in the diagnosis of PSP are reviewed. New
      terminology for the clinical diagnostic criteria for PSP is proposed. The main
      neuropathologic and neurochemical features supporting current main symptomatic
      and hypothesized experimental biologic therapies are suggested.

PMID- 11346025
TI  - Corticobasal degeneration.
AB  - Corticobasal degeneration (CBG) is an increasingly recognized neurodegenerative
      disease with both motor and cognitive dysfunction. The diagnosis is probably
      underestimated because of the heterogeneity of clinical features, overlap with
      symptoms, and pathologic findings of other neurodegenerative diseases. The most
      characteristic initial motor symptoms are akinesia, rigidity, and apraxia.
      Dystonia and alien limb phenomena are frequently observed. There is often a
      parkinsonian picture with failure or lack of efficacy of dopaminergic medical
      therapy. Cognitive decline, prompting the diagnosis of dementia, may be the most
      common presentation of CBD that is misdiagnosed. Pathology is characterized by an
      asymmetric frontoparietal neuronal loss and gliosis with ballooned, achromatic
      cortical neurons, nigral degeneration, and variable subcortical involvement.
      Neuroimaging and electrophysiologic studies may help with the diagnosis but are
      not specific. Treatment is primarily symptomatic and minimally effective,
      especially after the first several years of symptoms. CBD should be considered in
      the differential diagnosis of patients with motor and cognitive dysfunction
      presenting with cortical and subcortical features. Further studies to elucidate
      molecular abnormalities and biological markers associated with CBD are needed to
      improve clinical diagnosis and treatment of patients with this disorder.

PMID- 11346026
TI  - Movement disorders induced by dopamine blocking agents.
AB  - Movement disorders are frequently due to dopamine blocking agents (DBAs)
      prescribed for psychiatric illnesses. DBAs are sometimes also prescribed
      inappropriately for other maladies. These drugs can cause a wide variety of
      involuntary movements, sometimes in combination. When these appear in the setting
      of psychiatric illnesses, the association is easy to recognize but the treatment
      remains a difficult problem. However, in other situations the diagnosis may be
      missed for extended periods of time, resulting in unnecessary diagnostic work-up
      and inappropriate therapy. The diagnosis depends on a compulsive drug history not
      only from the patient but also from patient's family, primary physician, and the
      pharmacist. The treatment options include removal of the offending agent or
      substitution with an atypical neuroleptic. Symptomatic treatments are varied and
      have an inconsistent effect on the movement disorders. Prevention remains the
      most important strategy.

PMID- 11346027
TI  - Familial (idiopathic) paroxysmal dyskinesias: an update.
AB  - The clinical, pathophysiological and genetic features of some of the familial
      (idiopathic) paroxysmal movement disorders are reviewed. The paroxysmal
      dyskinesias share features and therefore may have the same pathophysiological
      mechanisms as other episodic neurological disorders which are known to be
      channelopathies. Paroxysmal kinesigenic choreoathetosis/dyskinesias (PKC/PKD) is
      a condition in which brief and frequent dyskinetic attacks are provoked by sudden
      movement. Antiepileptics particularly carbamazepine are very helpful for this
      condition. PKC has similarities to episodic ataxia type 1 which is caused by
      mutations of the KCNA1 gene. PKC and a related disorder in which infantile
      convulsions are associated (ICCA syndrome) have recently been linked to the
      pericentromic region of chromososme 16 in the vicinity of some ion channel genes.
      Paroxysmal exercise-induced dystonia (PED) is a rare disorder manifesting as
      episodes of dystonia mostly affecting the feet induced by continuous exercise
      like walking or running. The pathophysiology of PED is unknown and antiepileptic
      drugs are generally unhelpful. In paroxysmal dystonic
      choreoathetosis/nonkinesigenic dyskinesias (PDC/PNKD) the attacks are of long
      duration and induced by a variety of factors including coffee, tea, alcohol and
      fatigue but not by sudden movement. The gene for familial PDC has been linked to
      chromosome 2q close to a cluster of ion channel genes. Paroxysmal nocturnal
      dyskinesia is now known to be a form of frontal lobe epilepsy in some cases which
      may be familial with an autosomal dominant inheritance and has been given the
      eponym ADNFLE. ADNFLE is a genetically heterogenous condition. Mutations of the
      neuronal nicotinic acetylcholine receptor gene that have chromosome 20q have been
      reported in some families with ADNFLE. However, another family with ADNFLE has
      been linked to chromosome 15 in the area of another nicotinic acetylcholine
      receptor gene. Thus the familial paroxysmal dyskinesias appear to be clinically
      and genetically heterogeneous.

PMID- 11346028
TI  - Unusual causes of hemifacial spasm.
AB  - Hemifacial spasm (HFS) has been defined as consisting of brief clonic jerking
      movements of the facial musculature, beginning in the orbicularis oculi with
      downward spreading to other facial muscles. HFS, perhaps the most common of the
      abnormal involuntary facial movements, has been classically ascribed to vascular
      loop compression at the root exit zone of the facial nerve. Causes other than
      such vascular loops are rare in the medical literature. Here we present three
      case studies in which the phenomenology of the HFS was atypical in onset and
      evolution. Using these three patients as introduction to the topic, we reviewed
      the literature of all cases of HFS with causes other than the vascular loop. In
      these three cases, HFS was caused by (1) a parotid gland tumor, (2) a
      cerebellopontine angle meningioma, and (3) an acoustic schwannoma. We also
      discuss the radiological findings as well as possible differences in the genesis
      of HFS and phenomenology in such cases and present recommendations on how to
      evaluate these patients.

PMID- 11346029
TI  - The botulinum toxins in the treatment of cervical dystonia.
AB  - The use of botulinum toxin to treat cervical dystonia (CD) has dramatically
      improved the quality of life of patients with this disabling, often painful
      disease. Two forms of toxins, botulinum toxin type A (BTX-A) and botulinum toxin
      type B (BTX-B), have each been studied in large multicenter trials in subjects
      with CD. A study of BTX-A demonstrated improvement of 5.15 to 10.65 degrees in
      head position using the Cervical Dystonia Severity Scale (CDSS) in those treated
      with BTX-A (trade name BOTOX) compared with placebo. A study in patients who
      continued to respond to BTX-A and a similarly designed study in patients who were
      resistant to BTX-A demonstrated statistical improvement in the Toronto Western
      Spasmodic Torticollis Rating Scale (TWSTRS) in those treated with BTX-B
      (evaluated as NeuroBloc) compared with placebo. The potential availability of
      both forms of toxin will allow physicians to offer further treatment options to
      patients with CD.

PMID- 11346030
TI  - Dopamine agonists.
AB  - Dopamine agonists provide an effective means of treating early, middle, and late
      stages of Parkinson's disease. This article outlines the advantages and
      disadvantages of dopamine agonists as compared with levodopa therapy. The
      features and costs of the four Food and Drug Administration-approved agonists
      (bromocriptine, pergolide, pramipexole, and ropinirole) and apomorphine, another
      agonist presently under investigation, are discussed.

PMID- 11346031
TI  - Neurosurgery for Parkinson's disease.
AB  - Medical therapy for Parkinson's disease (PD) often becomes inadequate over
      several years. Disability increases despite maximal medical management and many
      patients develop motor fluctuations and dyskinesia. In addition, medications
      provide good control of tremor in only 50% of cases. In appropriately selected
      cases, surgical therapies for PD provide benefit for medically refractory
      symptoms. Recent advances have provided a greater array of surgical options.
      Unilateral thalamotomy and thalamic stimulation are considered safe and effective
      procedures to treat contralateral tremor. Pallidotomy and pallidal stimulation
      primarily reduce contralateral dyskinesia, with lesser effects on bradykinesia
      and rigidity. Studies indicate that subthalamic nucleus (STN) stimulation
      improves "off" period function, decreases "off" time, and lessens dyskinesia.
      Fetal cell transplantation remains experimental, and studies are underway to
      evaluate the safety and efficacy of porcine fetal cell and human retinal pigment
      epithelial cell transplantation. This chapter reviews the history of surgical
      procedures for PD, describes current procedures, and offers a look into the
      future of neurosurgical options for PD.

PMID- 11346032
TI  - Trace metal accumulation in Clarias gariepinus (Teugels) exposed to sublethal
      levels of tannery effluent.
AB  - The concentration and distribution of Cr, Cu, Pb and Zn among the tissues of a
      freshwater fish, Clarias gariepinus exposed to combined (composite) tannery
      effluent was investigated at two sublethal concentrations (2 and 6%) in static
      bioassay for 8 weeks. The distribution of the four metals in fish was of the
      order of Pb > Cr > Cu > Zn and the accumulation was found to be dose- and time
      dependent. The metal levels in the liver were significantly higher (P > 0.05)
      than other tissues. This was followed by the gill and the gut. Relatively low
      accumulation of these metals was found in muscle tissue.

PMID- 11346033
TI  - Health effects of fluoride pollution caused by coal burning.
AB  - Recently a huge amount of fluoride in coal has been released into indoor
      environments by the combustion of coal and fluoride pollution seems to be
      increasing in some rural areas in China. Combustion of coal and coal bricks is
      the primary source of gaseous and aerosol fluoride and these forms of fluoride
      can easily enter exposed food products and the human respiratory tract. Major
      human fluoride exposure was caused by consumption of fluoride contaminated food,
      such as corn, chilies and potatoes. For each diagnostic syndrome of dental
      fluorosis, a log-normal distribution was observed on the logarithm of urinary
      fluoride concentration in students in China. Urinary fluoride content was found
      to be a primary health indicator of the prevalence of dental fluorosis in the
      community. In the fluorosis areas, osteosclerosis in skeletal fluorosis patients
      was observed with a high prevalence. A biochemical marker of bone resorption,
      urinary deoxypyridinoline content was much higher in residents in China than in
      residents in Japan. It was suggested that bone resorption was stimulated to a
      greater extent in residents in China and fluoride may stimulate both bone
      resorption and bone formation. Renal function especially glomerular filtration
      rate was very sensitive to fluoride exposure. Inorganic phosphate concentrations
      in urine were significantly lower in the residents in fluorosis areas in China
      than in non-fluorosis area in China and Japan. Since airborne fluoride from the
      combustion of coal pollutes extensively both the living environment and food, it
      is necessary to reduce fluoride pollution caused by coal burning.

PMID- 11346034
TI  - A review of the calculation procedure for critical acid loads for terrestrial
      ecosystems.
AB  - Target loads for acid deposition in the Netherlands, as formulated in the Dutch
      environmental policy plan, are based on critical load calculations at the end of
      the 1980s. Since then knowledge on the effect of acid deposition on terrestrial
      ecosystems has substantially increased. In the early 1990s a simple mass balance
      model was developed to calculate critical loads. This model was evaluated and the
      methods were adapted to represent the current knowledge. The main changes in the
      model are the use of actual empirical relationships between Al and H
      concentrations in the soil solution, the addition of a constant base saturation
      as a second criterion for soil quality and the use of tree species-dependant
      critical Al/base cation (BC) ratios for Dutch circumstances. The changes in the
      model parameterisation and in the Al/BC criteria led to considerably (50%) higher
      critical loads for root damage. The addition of a second criterion in the
      critical load calculations for soil quality caused a decrease in the critical
      loads for soils with a median to high base saturation such as loess and clay
      soils. The adaptation hardly effected the median critical load for soil quality
      in the Netherlands, since only 15% of the Dutch forests occur on these soils. On
      a regional scale, however, critical loads were (much) lower in areas where those
      soils are located.

PMID- 11346035
TI  - C3 to C9 hydrocarbon measurements in the two largest cities of Greece, Athens and
      Thessaloniki. Calculation of hydrocarbon emissions by species. Derivation of
      hydroxyl radical concentrations.
AB  - Non-methane hydrocarbon concentrations (NMHC) were determined in samples
      collected in electropolished canisters aboard a Falcon aircraft in Athens and
      Thessaloniki. Some canisters were also collected on the ground in Athens.
      Chemical analysis by cryoconcentration permitted the speciation of NMHC. The
      aircraft samples allowed the determination of the background concentrations in
      the periphery of each city. Concentration ratios were compared with other
      European cities. The aromatic hydrocarbon fraction dominates the measured
      species. Using the simple box model modified to account for the chemical
      destruction of each hydrocarbon, the emissions for each species were determined
      in Athens and Thessaloniki. The hydroxyl radical concentrations were calculated
      using hydrocarbon concentration ratios in the urban areas and at a downwind
      distance.

PMID- 11346036
TI  - Dynamics of glyphosate and aminomethylphosphonic acid in a forest soil in
      Galicia, north-west Spain.
AB  - Residues of the herbicide glyphosate (N-phosphonomethylglicine) and its main
      metabolite, aminomethylphosphonic acid (AMPA), were determined in a forest soil
      in north-west Spain, previously treated with 5 and 8 l ha(-1) of glyphosate. Both
      products were monitored in the solid and liquid soil phases for an 8-week period
      after the treatment. Soil samples were extracted by KH2PO4. Concentrated extracts
      and liquid phase samples were derivatized with 9-fluorenylmethyl chloroformate
      (FMOC) before determination by HPLC using an anion exchange column and
      spectrofluorometric detection. The treated soil peaked at 6.9 microg g(-1) of
      glyphosate, whereas soil water samples peaked at 0.74 microg ml(-1) of
      glyphosate. One month after the treatment, both glyphosate and AMPA
      concentrations in soil and water samples were almost negligible. AMPA peaked at
      0.77 microg ml(-1) in soil water samples. Glyphosate and AMPA exhibited high
      vertical mobility in the treated soil, quickly reaching high concentrations in
      subsurface horizons where the degradation is slower.

PMID- 11346037
TI  - The long-term evolution of and transport processes in a self-sustained final
      cover on waste deposits.
AB  - A new principle for confinement of waste based on a self-sustained seal is
      presented. The top cover is considered to consist of two main layers; an organic
      carbon rich surface layer that is able to support vegetation and an inorganic
      layer beneath it. The function of the cover is to mitigate oxidation and
      acidification of landfilled waste and hence the release of toxic metals. It is
      suggested that forest soil formation and soil development could prove to be
      valuable information sources for the study of the long-term behaviour of a final
      cover on waste deposits. Since the cover is expected to develop in northern
      temperate climate the focus is on Spodosol soil. A number of simulations of the
      long-term behaviour of the final self-sustained landfill cover are made,
      including the rates of influx of oxygen into the cover. A cover having a large
      portion of organic matter compared with a cover with no organics can considerably
      decrease the oxygen concentration and thus the influx of oxygen into a landfill.
      The calculated oxygen intrusion rate for the former case is of the order of 0.05
      kg m(-2) year(-1). Degradation of the organics produces acids. Our simulations
      indicate that the pH-buffering capacity of the mineral layer, represented by
      calcite and primary rock minerals, will last for many thousands of years.

PMID- 11346038
TI  - Energy metabolism and carcinogenesis.

PMID- 11346039
TI  - The environmental impact of heavy metals from sewage sludge in ferralsols (Sao
      Paulo, Brazil).
AB  - The spreading of sewage sludge on acidic ferralsol soil was simulated in a column
      experiment in order to estimate the potential impact on water and soil quality.
      Drainage and runoff water were sampled daily over a 2-month experiment and
      analysed for Fe, Ni, Cu, Pb and DOC. Results show a clear influence of the sludge
      on the water quality, especially at the start of the experiment, increasing the
      export of Cu, Ni, Pb and in DOC from the soil, mainly in dissolved form. Nickel
      was usually the most mobile element in the sludge and in the soil. In the soil,
      Pb mobility was complex and increased drastically with time compared to the other
      elements. No significant increase in soil heavy metal content due to the sludge
      spreading was recorded on this time scale.

PMID- 11346040
TI  - Toxicity assessment of total dissolved solids in effluent of Alaskan mines using
      22-h chronic Microtox and Selenastrum capricornutum assays.
AB  - In order to overcome limitations associated with the Daphnia assay, we have
      explored two alternative assays, the 22-h chronic Microtox test and the 3-day S.
      capricornutum test, as substitutes. During this study, we compared the two assays
      using both a simple TDS standard solution and field water samples from two
      Alaskan mines. Using EC20 values, our results suggest that simple TDS standard
      solutions are not representative of environmental water samples of equivalent TDS
      concentrations. When comparing assays, our results showed that the 22-h Microtox
      assay was more reproducible and sensitive to effluent waters than the algal
      assay. Principle component analysis indicated that the 22-h Microtox test was
      generally more sensitive to nickel, ammonia and chloride while the S.
      capricornutum growth test appeared sensitive to cadmium levels.

PMID- 11346041
TI  - Ability of fractionated petroleum refinery effluent to elicit cyto- and
      photocytotoxic responses and to induce 7-ethoxyresorufin-O-deethylase activity in
      fish cell lines.
AB  - The ability of fractionated petroleum refinery effluent to cause cellular
      responses in fish cell lines was evaluated. The cellular responses, which
      included direct and indirect cytotoxicity, photocytotoxicity and induction of 7
      ethoxyresorufin-O-deethylase (EROD) activity, may potentially be linked to
      sublethal effects observed in effluent-exposed fish and fish larvae. In order to
      be able to quantify cellular responses rapidly, microtitre plates were used along
      with fluorescent probes. For the quantification of cyto- and photocytotoxicity,
      the fluorescent probes were alamar Blue and carboxyfluorescein diacetate
      acetoxymethyl ester (CFDA-AM), which monitor metabolic activity and cell membrane
      integrity, respectively. EROD activity was measured as the rate of conversion by
      EROD of the substrate 7-ethoxyresorufin to its fluorescent product, resorufin.
      Effluent from an Ontario refinery was fractionated into aqueous and particulate
      phase. As well, a solid phase extract (SPE) was used to prepare concentrated
      effluent for testing in the cell lines. The effluent was able to elicit all of
      the responses of interest although significant cyto- and photocytotoxicity
      required effluent equivalent concentrations above 100% effluent and could only be
      revealed upon exposure of cells to the SPE concentrated effluent. Based on their
      retention on C18, the cytotoxicants are likely to be non-polar to moderately
      polar chemicals. The presence of polar compounds affecting cellular metabolism
      was indicated by the responses of exposed cells to a 90% aqueous phase effluent.
      In contrast to cyto- and photocytotoxicity, EROD induction occurred at effluent
      equivalent concentrations well below 100% effluent and was elicited by the SPE
      and the particulate fraction thereby suggesting that most EROD-inducers were
      particle-bound. Among other applications, the described techniques could help to
      determine the source of causative agents of sublethal effects in the refining
      process.

PMID- 11346042
TI  - Relationship between soil lead and airborne lead concentrations at Springfield,
      Missouri, USA.
AB  - This study tests whether lead deposited to soil from automobiles during past
      years in a medium-sized US city (population 150,000) may present a current health
      risk. It examines the relationship between current soil lead concentrations at
      nine locations within the city of Springfield, Missouri, and airborne lead levels
      measured at the same locations during years (1975-1981) when lead emissions from
      automobiles were much greater than at present. A strong, significant correlation
      is found between soil and airborne lead levels at eight of the sites (r = 0.91, P
      < 0.005 for soil lead vs. 1979 airborne lead), in low-traffic areas as well as in
      areas adjacent to heavy traffic flow. Residual lead concentrations in these soils
      are relatively low, even for the high-traffic sites, as expected for a medium
      sized city.

PMID- 11346043
TI  - Sequential analysis of hair mercury levels in relation to fish diet of an
      Amazonian population, Brazil.
AB  - Several studies in the Amazonian Basin have shown that riverine populations are
      exposed to methylmercury through fish consumption. It has been suggested that
      seasonal variations in hair mercury observed through sequential analyses may be
      related to the changes in fish species ingested by the local communities. The aim
      of the present study was to investigate the relationship between fish-eating
      practices and seasonal variation in mercury exposure. A group of 36 women from a
      village located on the banks of the Tapajos River, a major tributary of the
      Amazon, comprised the present study population. An interview-administered
      questionnaire was used to gather information on socio-demographic
      characteristics, fish-eating practices and other relevant information. The women
      also provided hair samples of at least 24 cm in length for mercury analysis. Hair
      total and inorganic mercury concentration was measured using a cold vapor atomic
      absorption analytical method. Trigonometric regression analysis was done to
      assess the seasonal variation of total mercury levels. Variations in inorganic
      mercury were examined by repeated measures analysis of variance, and analysis of
      contrast variable with a polynomial transformation. The results showed that hair
      mercury levels varied with the season. Higher levels were observed in months
      corresponding to the dry season, with lower levels in the rainy season.
      Herbivorous fish predominated the diet for 47.2% of the women during the dry
      season, but this rose to 72.2% during the rainy season. Those who reported eating
      fish daily had higher mercury levels in hair compared to those who only ate fish
      a few times per week. Retrospective mercury analyses, evaluated by the quantity
      of mercury present in each centimeter of hair, indicate that mean mercury level
      of the population decreased over the 2 years prior to the study. The percentage
      of inorganic mercury over the total mercury in hair increased towards the
      extremities of the hair strand. Higher percentages of inorganic mercury were
      found for the group who ate more fish (on a daily consumption basis). These
      results support the assumption that there are seasonal variations in
      methylmercury exposure and also a relationship between type of fish species
      consumed and the resulting hair mercury levels.

PMID- 11346044
TI  - Blood lead content in a peri-urban population of the South American toad Bufo
      arenarum.
AB  - Blood Pb concentration in a South American toad Bufo arenarum population (n =
      152) was determined over 10 samplings carried out between December 1996 and
      November 1999. The studied population lived in the surroundings of the La Plata
      City, the largest industrial-urban setting of the Buenos Aires Province,
      Argentina. The presence of the metal was detected in all the samples tested, the
      mean concentration range being 1.99-4.66 mg dl(-1). Some preliminary
      environmental data on soil content of Pb in the sampling area suggest the
      anthropogenic origin of the metal possibly due to high rate of Pb-containing
      gasoline utilisation until recently. The reported results may reflect a sequel of
      a sustained local air-soil-water pollution process.

PMID- 11346045
TI  - The interaction of maternal and infant vulnerabilities on developing attachment
      relationships.
AB  - The present study sought to document an example of how maternal and infant
      vulnerabilities interact in contributing to the quality of early attachment
      relationships. Maternal depressive symptoms, neonatal health characteristics, and
      infant mother attachment were assessed for 42 preterm, low birth weight infants
      and 42 full-term infants at 12 months postterm. Results indicated that preterm
      birth moderated the relation between maternal depressive symptoms and quality of
      infant-mother attachment, even controlling for level of neonatal health
      complications. Preterm infants with more symptomatic mothers were most likely to
      be classified as insecurely attached to their mothers, whereas no direct relation
      between subclinical depressive symptoms and attachment was found for full-term
      infants.

PMID- 11346046
TI  - Prototype formation in autism.
AB  - Individuals with autism have difficulty integrating information and generalizing
      previously learned concepts to new situations. It was hypothesized that these
      problems result from an underlying impairment in category formation. Persons with
      autism may not abstract a summary representation (a prototype) during category
      learning and, instead, may form categories by memorizing a list of rules.
      Children with autism, Down syndrome, and normal development participated in one
      set of category learning tasks that could be solved using a rule-based approach
      and a second set of tasks in which there was no rule that defined category
      membership (prototype tasks). In the rule-based tasks, all groups were successful
      at using a rule to learn a new category. In the prototype tasks, only the
      typically developing children were able to learn a new category. Neither the
      persons with autism nor the persons with Down syndrome appeared to develop a
      prototype during category learning. These data suggest that persons with autism
      and Down syndrome have difficulty categorizing new information by forming
      prototypes and, instead, tend to rely on a rule-based approach to learning.

PMID- 11346047
TI  - Parent participation in community activities and the persistence of criminality.
AB  - This study assessed whether the lack of parental participation in community
      activities during late childhood is significantly related to the persistence of
      criminal activity from adolescence to adulthood. A prospective, longitudinal
      investigation of a representative cohort of 548 boys from a middle-sized Swedish
      community was employed. A pattern-oriented analysis identified five
      configurations of boys who showed different profiles of social and academic
      competence at the age of 13 years. The configurations were compared with respect
      to persistent criminality among the boys for parents who did, and who did not,
      show stable participation in a community activity when their sons were in late
      childhood. Fathers engaged in a community activity had sons with significantly
      lower rates of persistent criminality. This result was most marked for youth with
      low school achievement, and multiple problem profiles of social and academic
      disadvantage. The findings held after controlling for family socioeconomic
      status. Mother's participation in community activities was statistically
      dependent on father participation but was not related to persistent offending
      among multiple problem boys. Results are discussed in terms of the different
      impact associated with mother and father community activity participation on
      persistent offending, and the holistic perspective to development guiding this
      research.

PMID- 11346048
TI  - Attachment stability and emotional and behavioral regulation from infancy to
      preschool age.
AB  - Relations between attachment and child emotional and behavioral regulation were
      studied longitudinally in a sample of 223 children from urban, low-income
      families. Attachment in the Strange Situation at 12 and 18 months was scored
      using the infant classification system and at 24 months was scored using a
      preschool classification system. Only modest stability was found in attachment
      whether within or across classification systems, with the percentage of insecure
      attachments consistently increasing over time. Results indicated both concurrent
      and predictive associations with indices of child regulation based on observer
      ratings or maternal report. However, only the 24-month classification predicted
      maternal report of externalizing and internalizing behavior problems at age 3.5
      years. with additional variance accounted for by selected measures of child
      emotional and behavior regulation from the same assessment. Attachment security
      (B) and atypical attachment classifications (D, A/C, and AD) appear to provide
      the most consistently useful information about child functioning. Results are
      discussed in terms of continuity and change from the perspective of developmental
      psychopathology.

PMID- 11346049
TI  - Depressive symptomatology in childhood and adolescence.
AB  - Antecedents of depressive symptomatology in childhood and adolescence were
      examined in a prospective longitudinal study of at-risk youth (n = 168) from
      families of lower socioeconomic status. Relations between family context factors,
      maternal depressive symptoms, and depressive symptoms in childhood and
      adolescence were examined, with a focus on early family relationship factors
      rarely available for analysis in longitudinal data sets. Results suggest the
      possibility of etiological differences between depressive symptoms in childhood
      and in adolescence. Depressive symptomatology in childhood was predicted by the
      overall family context. Cumulative effects of maternal depressive symptomatology,
      early care lacking in emotional supportiveness, abuse, and family stressors were
      observed. Depressive symptomatology in adolescence, on the other hand, was
      specifically associated with maternal depression and early care lacking in
      emotional supportiveness. Moreover, an intriguing sex difference emerged:
      maternal depressive symptomatology was strongly associated with depressive
      symptomatology in adolescence for females, but for males supportive early care
      appeared more relevant.

PMID- 11346051
TI  - Intrafamily conflict in relation to boys' adjustment at school.
AB  - Several theoretical models of child development have posited the spread of
      conflict within families; however, few researchers have studied this process in
      association with relationships children have with teachers and peers at school.
      The present study examined the direct, additive, and interactive contributions of
      interparental, parent-child, and sibling conflict in relation to teacher-child
      and child-peer conflict in a sample of 117 low-income boys from ages 3.5 to 6
      years. Overall, the results suggest that while conflict in any one dyadic family
      relationship is only modestly associated with later conflictual relationships at
      school, risk for conflict in relationships with teachers and peers increases when
      multiple forms of early family conflict are experienced. Results are discussed in
      terms of the development of conflict across early relationships.

PMID- 11346050
TI  - Developmental themes in women's emotional experiences of motherhood.
AB  - In this study, women's levels of ego development and their psychological
      difficulties were examined in relation to feelings in the maternal role. The
      sample consisted of 91 mothers from diverse socioeconomic backgrounds. Ego
      development was assessed by the Washington University Sentence Completion Test,
      and psychological difficulties were operationalized by self-reported global
      symptomatology, maternal substance abuse, and expressed anger. Outcome variables
      included feelings of satisfaction, distress, and support in the maternal role, as
      well as the degree to which negative and positive emotions were integrated in
      response to hypothetical vignettes of challenging everyday child-rearing
      experiences. Hypotheses were that women at high levels of ego development would
      show greater deterioration in the presence versus absence of self-reported
      adjustment problems than would those at lower levels. A series of interaction
      effects each indicated trends consistent with the hypotheses. These results add
      to accumulating evidence that tendencies toward self-examination, characteristic
      of high developmental levels, do not inevitably serve protective functions but
      may be linked with heightened reactivity to negative intrapsychic forces.

PMID- 11346052
TI  - Emotion knowledge in economically disadvantaged children: self-regulatory
      antecedents and relations to social difficulties and withdrawal.
AB  - We examined the relations of verbal ability and self-regulation in preschool to
      emotion knowledge in first grade, and concurrent relations between emotion
      knowledge and indexes of social functioning in 143 children from low-income
      families. After controlling for children's verbal ability in preschool, teacher
      reports of attentional control and caregiver reports of behavioral control in
      preschool predicted children's emotion expression knowledge and emotion situation
      knowledge 2 years later. After controlling for verbal ability and attentional and
      behavioral control, children's emotion knowledge predicted concurrent teacher
      reported social problems and social withdrawal. Results suggest that low levels
      of emotion knowledge co-occur with many important aspects of children's early
      social adaptation.

PMID- 11346053
TI  - A longitudinal examination of the associations between mothers' and sons'
      attributions and their aggression.
AB  - This study tested an integrative, multipathway model designed to explain
      bidirectional effects of the attributions and coercive behaviors of mothers and
      sons in the context of a longitudinal study. Subjects were 246 mothers and sons
      who were 7-9 years of age. Mothers' and sons' attributions about one another's
      intent were significantly related to the aggressiveness of the behavior that each
      of them directed toward the other. Boys' earlier aggression did not significantly
      predict the mothers' subsequent attributions, whereas mothers' negative behavior
      indeed predicted subsequent negative attributions on the part of the boys. Even
      after considering children's earlier negative behavior, children's negative
      attributions about their mothers helped explain the aggressiveness of their
      subsequent behavior. The same was not true for mothers whose earlier attributions
      indirectly influenced their subsequent aggressive behavior.

PMID- 11346054
TI  - The quality of peer relationships among children exposed to family violence.
AB  - Three hundred sixty-three school-aged children from maritally violent and
      nonviolent families were interviewed about their friendship networks, frequency
      of social contact, the interpersonal quality of their friendships, and hostile
      attributional biases. Mothers answered items from the Child Behavior Checklist
      about peer conflict. Children did not differ on the number of friends they
      claimed or their frequency of contact with peers. However, children exposed to
      marital violence reported feeling more lonely and having more conflict with a
      close friend. Their mothers also reported them as having more problems with
      peers. In addition, children with punitive mothers had more conflict with a best
      friend. Residing in a shelter added further to children's feelings of loneliness,
      with one third having no best friend. Children's attributional biases were
      unrelated to the quality of their peer relations or any other index of peer
      functioning. Results are discussed in terms of an attachment framework. Findings
      confirm that it is important to examine the quality of relationships to determine
      how children at risk fare in their social lives.

PMID- 11346055
TI  - The execution of arbitrary procedures by children with autism.
AB  - Executive tasks typically contain a prepotent lure. In addition, they require
      individuals either to (a) follow arbitrary procedures or (b) update their model
      of the physical world. Recent research suggests that children with autism may be
      challenged only by executive tasks of the former kind (containing arbitrary
      rules). We asked whether this continues to be true when there is no prepotent
      lure, comparing performance on (a) a task with arbitrariness but without
      prepotency with (b) a task with both features and (c) a task with neither. The
      participants with autism performed at a lower level than comparison groups on the
      first and second task but not on the third task. This outcome is consistent with
      the view that autism is associated with difficulties in following arbitrary
      procedures per se. We try to locate difficulties with acting on the basis
      arbitrary rules in relation to more mainstream ideas about autistic executive
      dysfunction.

PMID- 11346056
TI  - Effect of levothyroxine administration time on serum TSH in elderly patients.
AB  - BACKGROUND: Standard drug information resources recommend that levothyroxine be
      taken on an empty stomach due to the potential for interaction with food or
      medications. Due to concern about unpredictable response to levothyroxine in
      patients receiving morning doses in a skilled nursing facility, the standard
      administration time for the drug was changed from 0900 to midnight. OBJECTIVE: To
      determine if a change in response to levothyroxine as determined by the serum
      ultrasensitive thyroid-stimulating hormone (TSH) concentration occurred when the
      time of administration was changed from early morning to midnight. DESIGN:
      Retrospective chart review. SETTING: A 187-bed skilled nursing facility.
      PARTICIPANTS: Fifteen nursing home residents receiving levothyroxine during the
      change of administration time with a mean age of 84 years met inclusion criteria,
      with at least one TSH concentration reported prior to and at least one serum TSH
      concentration reported after the change in administration time to mignight.
      MEASUREMENTS: Serum TSH concentrations. RESULTS: There was a decrease in serum
      TSH of 0.286 +/- 1.722 mU/mL (mean +/- SD) after changing the administration time
      to midnight that was not statistically significant (t = 0.643; p = 0.532).
      CONCLUSIONS: Based on the results of the study, we conclude that levothyroxine
      could be routinely administered after breakfast.

PMID- 11346057
TI  - Antiepileptic hypersensitivity syndrome in children.
AB  - OBJECTIVE: To assess clinical features and outcomes of childhood antiepileptic
      hypersensitivity syndrome (AHS). AHS is an idiosyncratic reaction to aromatic
      anticonvulsants that can result in severe multiorgan dysfunction and death.
      METHODS: Children with suspected AHS (fever, rash, lymphadenopathy, liver
      dysfunction) were identified by an in-house computerized adverse drug event
      reporting system. The medical charts of children with suspected AHS were
      reviewed. A MEDLINE search (from 1966 to October 1999) was performed using the
      term antiepileptic hypersensitivity syndrome. RESULTS: Fourteen of 36 children
      who experienced a rash, urticaria, pruritus, fever, or hepatotoxicity associated
      with aromatic anticonvulsants met the criteria for AHS (mean age 10.4 +/- 6.5 y;
      males to females 8:6, white to African-American to biracial 10:3:1). Eight
      patients were receiving phenytoin, six carbamazepine, and four phenobarbital
      alone or in combination. The mean time from exposure to development of symptoms
      was 23.0 +/- 14.8 days. In addition to rash and fever (present in all patients by
      definition), other common features of AHS were lymphocytosis (71.4%), elevated
      erythrocyte sedimentation rate (64.3%), elevated aminotransferases (64.3%),
      lymphadenopathy (57.1%), eosinophilia (42.8%, coagulopathy (42.8%), leukocytosis
      (35.7%), leukopenia (35.7%), hyperbilirubinemia (35.7%), and nephritis (7.1%).
      All children recovered except one, who died from complications of liver failure.
      Clinical outcome was simimlar between children who received systemic steroid
      therapy (n=5) and those who did not. Antiepileptics producing AHS were
      discontinued in all patients. CONCLUSIONS: AHS can be fatal in children if not
      promptly recognized. Fever, rash, and hepatotoxicity should serve as presumptive
      evidence for AHS, which requires immediate discontinuation of an offending
      anticonvulsant.

PMID- 11346058
TI  - Medication adherence in elderly patients receiving home health services following
      hospital discharge.
AB  - OBJECTIVE: To assess prevalence and risk factors for medication under- and
      overadherence in a two-week period following hospital discharge in adults > or =
      65 years. DESIGN: Prospective, cohort study. SETTING: Three home healthcare
      agencies in Madison, Wisconsin, and surrounding vicinity. PARTICIPANTS: One
      hundred forty-seven older participants taking three or more medications who were
      hospitalized for medical illness, received home nursing after discharge, and
      completed the two-week interview. MEASUREMENTS: The main outcome measures were
      having at least one medication with less than 70% adherence (underadherence) and
      having at least one medication with more than 120% adherence (overadherence)
      based on pill counts. RESULTS: Forty-five (30.6%) participants were underadherent
      and 27 (18.4%) participants were overadherent with at least one medication> In a
      multivariate model, underadherence was predicted by poor cognition (OR 2.5; 95%
      CI 1.02 to 6.10) and higher medication use (OR 1.16; 95% CI 1.03 to 1.31, for
      each 1-unit increase in number of medications). Both poor cognition and low
      education were significantly associated with overadherence in univariate
      analysis; however, neither variable was significant once included in the
      multivariate model. CONCLUSIONS: Under- and overadherence to medications is
      common after hospital discharge. Poor cognition and a greater number of
      medications were associated with underadherence. Poor and lower education were
      markers for overadherence; however, further study is needed to determined whether
      these are independent predictors. Patients who have impaired cognition or are
      taking a greater number of medications after hospitalization may benefit from
      targeted interventions to monitor and improve medication compliance.

PMID- 11346059
TI  - Psychometric evaluation of four HIV disease-specific quality-of-life instruments.
AB  - OBJECTIVE: To provide a comparative evaluation of psychometric properties for
      three or more HIV disease-specific quality-of-life (QoL) instruments. METHODS:
      Four instruments were selected using the following criteria: multiple publiations
      of instrument, focus of instrument on QoL, psychometric validation publication or
      comparison with prevoiusly validated questionnaire, stages of HIV/AIDS used or
      evaluated in the study, and inclusion of sample items or the instrument in at
      least one publication. The four HIV-specific QoL instruments were: HIV/AIDS
      Targeted Quality of Life Instrument, Medical Outcomes Study HIV questionnaire
      (MOS-HIV), Functional Assessment of Human Immunodeficiency Virus Infection, and
      HIV Overview of Problems -- Evaluation System. These instruments were evaluated
      using combined criteria derived from McHorney and Tarlov and Shumaker et al. The
      criteria include: administration, content, depth, reliability, validity, and
      responsiveness. A letter grade scale (A,B,C,D) was used in rating the criteria.
      RESULTS: No instrument demonstrated ideal psychometric properties. The MOS-HIV
      questionnaire was the only instrument that published results for seven of the
      eight categories. Therefore, a decision cannot be made about the best instrument
      to use for measuring QoL in an HIV-positive patient. CONCLUSIONS: Published data
      for these questionnaires had common limitations of sample size, study design, and
      population demograhpics, Hence, further testing of these questionnaires is
      recommended before use in any study to determine suitability, reliability and
      validity.

PMID- 11346060
TI  - Nelfinavir desensitization.
AB  - OBJECTIVE: To report the first case of nelfinavir desensitization in an HIV
      patient who was intolerant to protease inhibitors. CASE SUMMARY: A 43-year-old
      HIV-positive white man was treated with several protease inhibitors. The patient
      developed rashes in response to all protease inhibitors. His viral load was
      controlled only in the presence of a protease inhibitor. The patient tolerated
      nelfinavir longer than the other agents; therefore, the decision was made to
      attempt to desensitize him to nelfinavir. A six-hour inpatient protocol was used,
      and he tolerated the procedure without event. His disease is now well managed
      without recurrence of the rash. DISCUSSION: The use of protease inhibitors has
      had a major impact on the morbidity and mortality of HIV-infected patients,
      Despite their benefits, this class of drugs is not without adverse effects.
      Allergic reactions in the form of rashes may develop, which can severely limit
      treatment options in HIV patients. We report the first case of rapid
      desensitization of nelfinavir in a patient who developed rashes to several
      protease inhibitors. CONCLUSIONS: Intolerance to protease inhibitors due to rash
      is a well-documented phenomenon. In HIV patients, this can limit treatment
      options severely. This case demonstrates how desensitization to nefinavir can be
      performed successfully.

PMID- 11346061
TI  - Treatment of neuropathic pain with venlafaxine.
AB  - OBJECTIVE: To report a case of successful treatment of neuropathic pain with
      venlafaxine. CASE REPORT: A 39-year-old white woman presented with neuropathic
      back pain. The patient obtained 50% pain relief with consecutive use of
      amitriptyline, desipramine, and imipramine. Anticholinergic effects prompted a
      switch to extended-release venlafaxine 75 mg/d. Pain relief was as effective with
      this therapy as with the tricyclic antidepressants. The absence of adverse
      effects allowed the patient to discontinue all laxatives. DISCUSSION: Venlafaxine
      is an antidepressant that inhibits reuptake of norepinephrine and serotonin. This
      is the major mechanism by which tricyclic antidepressants relieve neuropathic
      pain. Venlafaxine does not bind to muscarinic-cholinergic, histaminic or alpha1
      adrenergic receptors responsible for the common adverse effects seen with
      tricyclic antidepressants. CONCLUSIONS: This report describes the efficacious use
      of venlafaxine in the treatment of neuropathic pain. Double-blind, randomized,
      controlled trials are needed to explore this further.

PMID- 11346062
TI  - Lithium intoxication due to carbamazepine-induced renal failure.
AB  - OBJECTIVE: To report the case of a patient with manic-depressive disorder who
      developed lithium intoxcation following carbamazepine-induced acute renal
      failure. CASE SUMMARY: A 33-year-old white man with bipolar manic-depressive
      disorder was treated with lithium for the last 18 months. Three weeks prior to
      admission, carbamazepine 600 mg was added to the drug regimen due to a recurrence
      of the psychiatric disorder. He was admitted wh signs of lithium intoxication.
      Acute renal failure due to carbamazepine-induced interstitial nephritis was
      diagnosed. DISCUSSION: The combination of carbamazepine and lithium is known to
      cause neurotoxicity. We describe a different interaction in which the toxic
      lithium concentrations were the result of carbamazepine-induced acute renal
      failure. CONCLUSIONS: When considering adding carbamazepine to lithium, careful
      follow-up of the patients is warranted to prevent this indirect drug in
      interaction.

PMID- 11346063
TI  - Olanzapine-induced diabetes mellitus.
AB  - OBJECTIVE: To report two cases of new-onset diabetes mellitus resulting after the
      initiation of olanzapine treatment. CASE SUMMARY: A 31-year-old African American
      man and a 44-year-old white man, both with schizoaffective disorder, developed
      diabetes mellitus within weeks or months of olanzapine initiation. DISCUSSION:
      Our reports of new-onset diabetes due to olanzapine are consistent with those in
      the literature. Although the mechanism is not yet known, it has been hypothesized
      that perhaps damage to the pancreatic islet cells, weight gain, dysregulation of
      the sympathetic system, and insulin resistance are contributing factors.
      CONCLUSIONS: Diabetes mellitus secondary to olanzapine use seems to be a rare
      occurrence. However, certain risk factors such as obesity, family history, and
      concomitant medications may predispose an individual to development of diabetes
      mellitus while taking olanzapine. An increased awareness of this reaction is
      essential in the treatment of patients at risk. Periodic serum glucose monitoring
      in these individuals may be warranted.

PMID- 11346064
TI  - Linezolid for the treatment of resistant gram-positive cocci.
AB  - OBJECTIVE: To provide a comprehensive review of linezolid, the first of a new
      class of antibiotics, the oxazolidinones. Therapeutic issues regarding the
      emergence of multidrug-resistant bacteria and a brief history of the
      oxazolidinones are also discussed. DATA SOURCES: A MEDLINE search (1966-March
      2001) was conducted to identify pertinent literature, including preclinical
      trials, clinical trials, and reviews. Unpublished clinical data, adverse effects,
      and dosing information were abstracted from product labeling. STUDY SELECTION:
      Clinical efficacy data were extracted from clinical trials, case reports, and
      abstracts that mentioned linezolid. Additional information concerning antibiotic
      resistance, the oxazolidinones, in vitro susceptibility and the pharmacokinetic
      profile of linezolid also was reviewed. DATA SYNTHESIS: Linezolid exhibits
      activity against many gram-positive organisms, including vancomycin-resistant
      Enterococcus faecium, methicillin-resistant Staphylococcus aureus, and penicillin
      resistant Streptococcus pneumoniae. Linezolid inhibits bacterial protein
      synthesis at an early step in translation and is rapidly and completely absorbed
      from the gastrointestinal tract following oral administration. Efficacy has been
      demonstrated in a number of unpublished clinical trials in adults with pneumonia,
      skin and skin structure infections, and vancomycin-resistant E. faecium
      infections. The adverse effect profile is similar to that of comparator agents
      (beta-lactams, clarithrornycin, vancomycin). CONCLUSIONS: Linezolid is the first
      oral antimicrobial agent approved for the treatment of vancomycin-resistant
      enterococci. Since the oxazoildinones have a unique mechanism of action and
      expanded spectrum of activity against virulent and highly resistant gram positive
      pathogens, linezolid is a valuable alternative to currently available treatment
      options. Clinical trials evaluating linezolid and other oxazolidinones for
      antibiotic-resistant gram-positive infections, as well as comparator studies
      comparing linezolid with other candidate drugs, such as quinupristin/dalfopristin
      and choramphenicol, will further define the role of linezolid.

PMID- 11346065
TI  - Role of antimicrobial therapy in acute exacerbations of chronic obstructive
      pulmonary disease.
AB  - OBJECTIVE: To define the role of antimicrobial therapy in the treatment of acute
      bronchitic exacerbations of chronic obstructive pulmonary disease (COPD) through
      review of placebo-controlled clinical trials. Specificalty, to determine the
      benefit of antimicrobial therapy on patient outcome. DATA SOURCES: Placebo
      controlled dinical trials identified by MEDLINE search (1957-December 1999).
      STUDY SELECTION AND DATA EXTRACTION: All placebo-controlled clinical trials that
      included COPD patients with no evidence of pneumonia or underlying asthma were
      included in the evaluation. DATA SYNTHESIS: The role of antimicrobial agents in
      the treatment of acute exacerbations of COPD is controversial. Patients with COPD
      are often chronically colonized with bacteria, and many exacerbations are due to
      nonbacterial causes. Four placebo-controlled clinical trials and a meta-analysis
      have demonstrated significant improvements in outcome for patients treated with
      an antibiotic versus placebo. In contrast, six studies failed to demonstrate
      statistical differences, possibly due to the small sample size and the
      subjectivity of outcome measures. Overall, the data suggest that the benefit of
      antimicrobial therapy in acute exacerbations of COPD may be related to
      exacerbation severity. CONCLUSIONS: Antimicrobial agents may have a beneficial
      effect in the treatment of acute exacerbations of COPD in certain patients.
      Pending further research in this area, we recommend antimicrobial therapy only
      for COPD patients with acute bronchitic exacerbations characterized by increased
      dyspnea, sputum volume, and purulence.

PMID- 11346066
TI  - Tacrolimus in dermatologic disorders.
AB  - OBJECTIVE: To review the data surrounding the use of tacrolimus for skin
      disorders. DATA SOURCES: Articles were obtained through a MEDLINE search of
      English-language literature (1990-May 2000); references of the retrieved
      publications were further reviewed for relevant literature. STUDY SELECTION:
      Orginal studies in humans regarding the use of tacrolimus for skin disorders were
      included. DATA EXTRACTION: The major outcomes extracted from the literature
      involved patient response to therapy and adverse effects. DATA SYNTHESIS:
      Tacrolimus offers an additional therapeutic approach to the treatment of
      immunologically based skin disorders. led trials and case reports indicates
      topical tacrolimus is a safe and effective alternative treatment in patients with
      atopic dermatitis. Case reports document efficacy in recalcitrant pyoderma
      gangrenosum, mucosal lichen planus, and ichthyosis linearis trolled trials and
      case reports indicate oral tacrolimus is effective in recalcitrant plaque
      psoriasis. Case reports document efficacy in recalcitrant pyoderma gangrenosum
      and leukocytclastic vascultis. The clinical utility of oral tacrolimus in skin
      disorders is limited due to potentially severe adverse effects such as
      infections, hypertension, hyperglcemia hyperkalemia, nephrotoxicity
      neurotoxicity, and increased risk of neoplasia. CONCLUSIONS: Most of the
      available data indicate short-term (3 wk to 3 mo) topical tacrolimus is a safe
      and effective treatment alternative for inflammatory skin disorders. Further
      study is needed to evaluate long-term safety and efficacy and to determine the
      best dosage regimen. Although oral tacrolimus has demonstrated efficacy in
      inflammatory skin disorders, the potenial for serious adverse effects limits its
      utility to third-line therapy for patients who are resistant to, or intolerant
      of, conventional therapies.

PMID- 11346067
TI  - New recommendations from the 1999 American College of Cardiology/American Heart
      Association acute myocardial infarction guidelines.
AB  - OBJECTIVE: To review literature relating to significant changes in drug therapy
      recommendations in the 1999 American College of Cardiology (ACC)/American Heart
      Association (AHA) guidelines for treating patients with acute myocardial
      infarction (AMI). DATA SOURCES: 1999 ACC/AHA AMI guidelines, English-language
      clinical trials, reviews, and editorials researching the role of drug therapy and
      primary angioplasty for AMI that were referenced in the guidelines were included.
      Additional data published in 2000 or unpublished were also included if relevant
      to interpretation of the guidelines. STUDY SELECTION: The articles selected
      influence AMI treatment recommendations. DATA SYNTHESIS: Many clinicians and
      health systems use the ACC/AHA AMI guidelines to develop treatment plans for AMI
      patients. This review highlights important changes in AMI drug therapy
      recommendations by reviewing the results of recent clinical trials. Insights into
      evolving drug therapy strategies that may impact future guideline development are
      also described. CONCLUSIONS: Several changes in drug therapy recommendations were
      included in the 1999 AMI ACC/AHA guidelines. There is emphasis on administering
      fibrin-specific thrombolytics secondary to enhanced efficacy. Selection between
      fibrin-specific agents is unclear at this time. Low response rates to
      thrombolytics have been noted in the elderly, women, patients with heart failure,
      and those showing left bundle-branch block on the electrocardiogram. These
      patient groups should be targeted for improved utilization programs. The use of
      glycoprotein (GP) IIb/IIIa receptor inhibitors in non-ST-segment elevation MI was
      emphasized. Small trials combining reduced doses of thrombolytics with GP
      IIb/IIIa receptor inhibitors have shown promise by increasing reperfusion rates
      without increasing bleeding risk, but firm conclusions cannot be made until the
      results of larger trials are known. Primary percutaneous coronary intervention
      (PCI) trials suggest lower mortality rates for primary PCI when compared with
      thrombolysis alone. However, primary PCI, including coronary angioplasty, is only
      available at approximately 13% of US hospitals, making thrombolysis the preferred
      strategy for most patients. Clopidogrel has supplanted ticlopidine as the
      recommended antiplatelet agent for patients with aspirin allergy or intolerance
      following reports of a better safety profile. The recommended dose of
      unfractionated heparin is lower than previously recommended, necessitating a
      separate nomogram for patients with acute coronary syndromes. Routine use of
      warfarin, either alone or in combination with aspirin, is not supported by
      clinical trials; however, warfarin remains a choice for antithrombotic therapy in
      patients intolerant to aspirin. Beta-adrenergic receptor blockers continue to be
      recommended, and emphasis is placed on improving rates of early administration
      (during hospitalization), even in patients with moderate left ventricular
      dysfunction. New recommendations for drug treatment of post-AMI patients with low
      high-density lipoprotein cholesterol and/or elevated triglycerides are included,
      with either niacin or gemfibrozil recommended as an option. Supplementary
      antioxidants are not recommended for either primary or secondary prevention of
      AMI, with new data demonstrating lack of efficacy vitamin E in primary
      prevention. Estrogen replacement therapy or hormonal replacement therapy should
      not be initiated solely for prevention of cardiovascular disease, but can be
      continued in cardiovascular patients already taking long-term therapy for other
      reasons. Bupropion has been added as a new treatment option for smoking
      cessation. As drug therapy continues to evolve in treating AMI, more frequent
      updates of therapy guidelines will be necessary.

PMID- 11346068
TI  - Octreotide for acute variceal bleeding.
AB  - OBJECTIVE: To review the use o f octreotide for acute variceal bleeding. DATA
      SOURCES: Articles were obtained through computerized searches involving MEDLINE
      (from 1997 to October 2000). Additionally, several textbooks containing
      information on the diagnosis and management of acute variceal bleeding were
      reviewed. The bibliographies of retrieved publications and textbooks were
      reviewed for additional references. STUDY SELECTION: All randomized studies and
      pharmacoeconomic evaluations that used octreotide therapy for acute variceal
      bleeding were considered. Randomized controlled trials and meta-analyses
      involving other therapies for treating variceal bleeding were also reviewed for
      possible inclusion. DATA EXTRACTION: The primary outcomes extracted from the
      literature were persistent or recurrent bleeding, need for endoscopic
      intervention or balloon tamponade, and mortality. DATA SYNTHESIS: Although both
      endoscopic therapies and medications are used to control bleeding and rebleeding
      episodes, the endoscopic approach has the additional goal of obliterating the
      varix. Since rebleeding episodes are common as long as the varix is present,
      endoscopic and medication therapies cannot be considered interchangeable based on
      bleeding control alone. However, octreotide by continuous intravenous infusion
      has demonstrated effectiveness in reducing blood loss and transfusion
      requirements as both an initial intervention (until definitive sclerotherapy can
      be performed) or as adjunctive therapy to endoscopic measures. Octreotide can be
      started quickly, has a relatively rapid onset of action, and does not require
      someone with endoscopy training to initiate. Additionally, octreotide is
      relatively free of significant adverse effects. CONCLUSIONS: While additional
      investigations are needed, particularly in the area of pharmacoeconomics, there
      is substantial evidence that octreotide is an efficacious therapy with relatively
      few adverse effects when used in the management of acute variceal bleeding.

PMID- 11346069
TI  - Newer dopamine agonists in the treatment of restless legs syndrome.
AB  - OBJECTIVE: To review the use of newer dopamine agonists pramipexole and
      ropinirole, in the treatment of restless legs syndrome (RLS). DATA SOURCES:
      Biomedical literature was accessed through MEDLINE (1990-June 2000); key terms
      included restless legs syndrome, pramipexole, ropinirole, and dopamine agonists.
      References cited in those articles were also evaluated. DATA SYNTHESIS: A number
      of small clinical studies of short duration have examined the use of pramipexole
      and ropinirole in the treatment of RLS. Patients treated with either agent
      demonstrated marked improvement in RLS symptoms with minimal adverse effects.
      Recent postmarketing surveillance of the use of these drugs for Parkinson's
      disease reported problems with daytime somnolence; thus, patients should be
      counseled appropriately. CONCLUSIONS: Although the published trials show
      promising results for efficacy of pramipexole and ropinirole in the treatment of
      RLS, they are subject to many limitations. At present, these agents can be
      considered a reasonable alternative after failure of traditional therapies for
      RLS, such as carbidopa/levodopa. The encouraging results underscore the need for
      a large double-blind study comparing pramipexole and ropinirole with traditional
      agents.

PMID- 11346070
TI  - Calcium-channel antagonists and nitrates in coronary artery bypass patients
      receiving radial artery grafts.
AB  - OBJECTIVE: To review the literature assessing the role of vasodilators for the
      prevention of vasospasm leading to graft failure in patients receiving the radial
      artery (RA) as a conduit in coronary artery bypass grafting (CABG). DATA SOURCE:
      A MEDLINE search (January 1966-May 2000) was performed using calcium-channel
      antagonists, nitrates, radial artery, and coronary artery bypass as key words.
      English-language articles were identified, and the references of these articles
      were used to further identify pertinent articles. DATA SYNTHESIS: RAs can be used
      as conduits in CABG. It has been suggested that failure of these grafts may be
      due to vasospasm, leading to occlusion observed angiographically. Calcium-channel
      antagonists and nitrates have been proposed as a means of preventing vasospasm
      and subsequent graft failure. CONCLUSIONS: Currently published data on the use of
      calcium-channel antagonist or nitrate therapy as prophylaxis against vasospasm in
      patients receiving RA grafts are inconclusive. Systematic evaluations of
      currently available pharmacologic agents are needed to guide clinical practice in
      this area.

PMID- 11346071
TI  - Common prescriptions in ambulatory care in Lebanon.
AB  - OBJECTIVE: To describe prescribing practices of family physicians in a staff
      model health maintenance organization at a university health center in Lebanon
      and estimate costs of such practices for common diseases. METHODS: All
      prescriptions issued between July 1, 1997, and June 30, 1998, were prospectively
      collected. The diagnoses made by physicians at each encounter were recorded, and
      the total price of medications prescribed was calculated. The core prescribing
      indicators as defined by the World Health Organization and the mean annual
      prescription price per person for the 25 most common diagnoses were calculated.
      RESULTS: Prescribing occurred in 27.1% of encounters, with a mean of 1.6
      medications per encounter; 17.5% of all prescriptions included an antibiotic.
      Generic drugs and essential drugs each accounted for 2.9% of all medications.
      Approximately 50% of the consultations for either respiratory or ear infections
      resulted in a prescription. Cervical spine syndromes and lipid metabolism
      disorders cost most among recorded diagnoses, with mean annual prescription
      prices per person of US $2016 and $1128, respectively. CONCLUSIONS: The low rate
      of generic and essential drug prescribing, as well as the frequency of
      prescribing in respiratory infections, highlight the need for initiatives to help
      rationalize prescribing in primary care in Lebanon. Together with the diagnostic
      categories incurring high cost per person, these issues can be part of physician
      education or treatment guideline development. These measures may aid the
      government in its subsidy of primary health care centers.

PMID- 11346072
TI  - Recurrent asymptomatic bradycardia episodes after cisplatin infusion.

PMID- 11346073
TI  - Desenitization to fluconazole in an AIDS patient.

PMID- 11346074
TI  - Dalteparin-induced extremity hematoma complicated by probable compartment
      syndrome.

PMID- 11346075
TI  - Vocational part-time training: jobs for the girls and boys.

PMID- 11346076
TI  - Implementing evidence-based guidelines.

PMID- 11346077
TI  - Can hepatitis C transmission be reduced in Australian prisons?

PMID- 11346078
TI  - The mental health of young Australians.

PMID- 11346079
TI  - Heart Week 2001: "Get active"! A call to action.

PMID- 11346080
TI  - Asthma screening as part of a routine school health assessment in the Australian
      Capital Territory.
AB  - OBJECTIVE: To determine the feasibility and performance of a routine screen for
      childhood asthma in new entrants to primary school relative to diagnosis by a
      paediatrician. DESIGN: Cross-sectional study with a validation substudy.
      PARTICIPANTS AND SETTING: All 4539 new primary school entrants (mean age, 5.72
      years; 95% CI, 5.71-5.74) in the Australian Capital Territory (ACT) in 1999; 180
      of these children (73% of the 248 contacted) participated in the validation
      substudy. MAIN OUTCOME MEASURE: Performance of the screening test relative to a
      paediatrician's diagnosis of current asthma (defined as a history of wheeze
      suggestive of a clinical diagnosis of asthma within the past 12 months) based on
      history and examination. RESULTS: 3748 of the 4539 new primary school entrants
      (83%) returned completed asthma and respiratory questions. The screening test was
      positive in 38% of children. Estimated sensitivity was 92% (95% CI, 75%-99%);
      specificity, 76% (95% CI, 72%-80%); positive predictive value, 51% (95% CI, 41%
      63%); negative predictive value, 98% (95% CI, 90%-100%); positive likelihood
      ratio, 3.8 (95% CI, 2.8-4.8); and negative likelihood ratio, 0.14 (95% CI, 0.02
      0.33). CONCLUSIONS: It is feasible to conduct population screens for asthma that
      have good diagnostic test performance against a specialist paediatrician's
      diagnosis through school health programs. This approach could facilitate
      monitoring changes in asthma prevalence over time.

PMID- 11346081
TI  - The contribution of maternal smoking to preterm birth, small for gestational age
      and low birthweight among Aboriginal and non-Aboriginal births in South
      Australia.
AB  - OBJECTIVES: To determine the contribution of maternal smoking to preterm birth (<
      37 weeks' gestation), small for gestational age (SGA, birthweight < 10th
      percentile for gestational age) and low birthweight (< 2500 g) among Aboriginal
      and non-Aboriginal births in South Australia. DESIGN: Retrospective cohort
      analysis of population-based perinatal data. SETTING: The State of South
      Australia, population 1.5 million. PARTICIPANTS: 36059 women (of whom 851 were
      Aboriginal women) who had singleton births in 1998-1999. MAIN OUTCOME MEASURES:
      Relative risks and population-attributable risks of preterm birth, SGA and low
      birthweight from smoking in the second half of pregnancy, by age and
      Aboriginality. RESULTS: Aboriginal women had a higher rate of smoking in
      pregnancy than non-Aboriginal women (57.8% v 24.0% at the first antenatal visit)
      and high rates for all age groups, while the rates decreased with age among non
      Aboriginal women. Heavy smoking increased with age, and Aboriginal women were
      heavier smokers. Women who smoked had elevated relative risks of preterm birth
      (1.64), SGA (2.28) and low birthweight (2.52), and all these showed a dose
      response relationship. Among Aboriginal (versus non-Aboriginal) births,
      population-attributable risks were significantly higher for SGA (48% v 21%, and
      59% for births to Aboriginal teenagers), low birthweight (35% v 23%) and preterm
      birth (20% v 11%). CONCLUSIONS: Health promotion programs, with a focus on
      smoking cessation and reducing uptake of smoking, need to be implemented in an
      appropriate cultural context, especially among young Aboriginal women. Such a
      program is being developed in South Australia.

PMID- 11346082
TI  - Evaluating the effectiveness of evidence-based guidelines for the use of spacer
      devices in children with acute asthma.
AB  - OBJECTIVE: To change standard practice from using nebulisers to metered dose
      inhalers and holding chambers (spacers) in children presenting with mild to
      moderate acute asthma. DESIGN: A before-after comparison of children with acute
      asthma presenting to the emergency department (ED) between August and October
      1999 with those presenting between June and August 1997. SETTING: A tertiary care
      metropolitan children's hospital. INTERVENTIONS: Evidence-based clinical practice
      guidelines for using spacers were developed by a local multidisciplinary
      consensus process. A multifaceted guideline implementation program was used in
      1999. MAIN OUTCOME MEASURES: Physician prescribing practices (spacer use);
      clinical outcomes (need for hospitalisation, admission to intensive care unit,
      and length of stay [LOS]). RESULTS: 75 of 247 children (30%; 95% CI, 25%-36%)
      required hospital admission in 1999. This was similar to the 1997 study period,
      when 95 of 326 (29%; 95% CI, 24%-34%) children were admitted. Of those with mild
      to moderate asthma, 160 (68%) received bronchodilators in the ED; 151 (94%) were
      initially treated with a spacer device in 1999. In 1997, no children were
      initially treated with spacers in the ED. The median (range) LOS in hospital for
      children with asthma of all severities was 1.7 (0.5-19.8) days in 1999 and 1.7
      (0.2-7.6) days in 1997 (P=0.85). CONCLUSIONS: We successfully changed standard
      practice from using nebulisers to spacers for bronchodilator delivery in children
      with mild to moderate acute asthma, with no difference in the need for or
      duration of hospitalisation.

PMID- 11346084
TI  - EBM in practice: internal medicine.
AB  - Specialists in internal medicine have a strong research and evidence culture, and
      there is a large evidence base, particularly for diagnostic tests and
      therapeutics. Deficiencies in evidence exist in the area of clinical diagnosis,
      including the sensitivity, specificity and positive and negative predictive
      values of clinical signs. The practice of evidence-based medicine (EBM) by
      internal medicine specialists is hindered by lack of clinical information support
      systems for ongoing practice evaluation, benchmarking and improvement. Many
      internal medicine practitioners are moving towards the use of clinical practice
      guidelines to aid the EBM process. A greater acceptance of EBM processes,
      including evaluation and guidelines, and resolving issues of distrust of
      bureaucracies, practitioner protection and consumer privacy, would increase the
      use of EBM in internal medicine.

PMID- 11346083
TI  - Percutaneous vertebroplasty: a novel treatment for acute vertebral fractures.
AB  - Acute vertebral fracture is a painful and debilitating complication of
      osteoporosis which has been extremely difficult to manage. Percutaneous
      vertebroplasty--injecting cement to stabilise the fractured end plate--represents
      a major management breakthrough. We report the first four patients with
      osteoporotic vertebral fractures treated by this technique at our hospital. They
      are, to our knowledge, among the first to be successfully treated in this way in
      Australia.

PMID- 11346085
TI  - EBM in practice: psychiatry.
AB  - Psychiatry was one of the first medical specialties to use the tools of evidence
      based medicine (EBM)--randomised controlled trials (RCTs), systematic reviews
      with meta-analyses--and as many treatment decisions in psychiatry are evidence
      based as in general medicine. Psychiatrists have some reservations about the EBM
      approach because of perceived limitations in methodology of RCTs and systematic
      reviews; gaps in the evidence base; problems interpreting the available evidence;
      and neglect of individual patient uniqueness in quantitative research based on
      groups or populations. Research supports the value of psychotherapy and there are
      now a number of empirically validated efficacious psychotherapies for a range of
      disorders.

PMID- 11346086
TI  - Ethical thinking and stakeholders.
AB  - Modern medical practice increasingly requires us to think beyond the confines of
      the doctor-patient relationship to other stakeholders. Problems and issues that
      can be identified as being of interest to a number of people are defined as
      "focal entities". Stakeholders are those with an interest in the outcome of the
      problem or issue. The salience of stakeholders is defined by their power,
      legitimacy and urgency. The process of thinking about stakeholders can help to
      clarify our ethical thinking about matters of importance to people beyond the
      doctor-patient relationship.

PMID- 11346087
TI  - Job-sharing in paediatric training in Australia: availability and trainee
      perceptions.
AB  - OBJECTIVE: To examine the current availability of job-sharing in paediatric
      training hospitals in Australia and to evaluate job-sharing from the trainees'
      perspective. DESIGN: National survey with structured telephone interviews and
      postal questionnai res. SETTING: The eight major paediatric training hospitals in
      Australia. PARTICIPANTS: Directors of Paediatric Physician Training (DPPTs) at
      each hospital (or a staff member nominated by them) provided information by phone
      interview regarding job-sharing. All paediatric trainees who job-shared in 1998
      (n=34) were sent written questionnaires, of which 25 were returned. RESULTS:
      Hospitals differed in terms of whether a trainee was required to give a reason
      for wishing to job-share, and what reasons were acceptable. One hospital stated
      that two specialty units (Intensive Care and Neonatal Intensive Care) were
      excluded from job-sharing, and another stated that certain units were unlikely to
      be allocated job-sharers. The remaining six hospitals said that all units were
      available for job-sharing, but the majority of their trainees disagreed. Only one
      hospital had a cap on the number of job-share positions available yearly.
      Trainees perceived benefits of job-sharing to include decreased tiredness,
      increased enthusiasm for work, and the ability to strike a balance between
      training and other aspects of life. Trainees believed job-sharing did not
      adversely affect the quality of service provided to patients, and that part-time
      training was not of lower quality than full-time training. CONCLUSIONS: Job
      sharing in Australian paediatric training hospitals varies in terms of the number
      of positions available, eligibility criteria, and which units are available for
      job-sharing. In our survey, trainees' experience of job-sharing was
      overwhelmingly positive.

PMID- 11346088
TI  - Part-time specialty training--my experience.

PMID- 11346089
TI  - 6: Movement disorders II: the hyperkinetic disorders.
AB  - Involuntary movements or hyperkinesias are classified into syndromes of chorea,
      ballism, tremor, dystonia, myoclonus and tics. The hyperkinesias are caused by
      disturbances in the circuitry connecting the cerebral cortex, thalamus, basal
      ganglia and cerebellum. Drugs are a common cause of movement disorders. The aim
      of management is to characterise the movement disorder, identify and treat the
      cause or institute symptomatic treatment. The genetic basis of many movement
      disorders is increasingly recognised. Where there are potential implications for
      family members, accurate diagnosis and counselling are particularly important.

PMID- 11346090
TI  - Is coenzyme Q10 helpful for patients with idiopathic cardiomyopathy?

PMID- 11346091
TI  - Pneumococcal disease in Australia: the immunological basis of pneumococcal
      vaccines.

PMID- 11346093
TI  - Management of unstable angina. Guidelines--2000.

PMID- 11346092
TI  - Management of unstable angina. Guidelines--2000.

PMID- 11346094
TI  - Depressed Australians: should we worry?

PMID- 11346095
TI  - Depressed Australians: should we worry?

PMID- 11346096
TI  - Serious complications with neck manipulations and informed consent.

PMID- 11346098
TI  - Pulling rural training initiatives together.

PMID- 11346097
TI  - Serious complications with neck manipulation and informed consent.

PMID- 11346099
TI  - Testicular cancer management.

PMID- 11346100
TI  - Antibiotics for community-acquired pneumonia: time to return to the straight and
      narrow?

PMID- 11346101
TI  - Gastro-oesophageal reflux disease: not so benign.

PMID- 11346102
TI  - White coats and the medical profession.

PMID- 11346103
TI  - Physician-assisted suicide: experience and controversy.

PMID- 11346104
TI  - The management of testicular cancer in Victoria, 1988-1993. Urology Study
      Committee of the Victorian Co-operative Oncology Group.
AB  - OBJECTIVES: To evaluate the patterns of care and management of testicular cancer
      in Victoria. DESIGN AND SETTING: Retrospective analysis of all cases of
      testicular cancer in Victoria from 1988 to 1993 identified through the Victorian
      Cancer Registry. MAIN OUTCOME MEASURES: Description of patient characteristics,
      staging investigations, initial management, and outcome. RESULTS: 667 eligible
      cases of testicular cancer were identified and questionnaires were returned for
      633 of these patients (94.9% response rate). There were 357 (56.4%) patients with
      pure seminoma; 271 (42.8%) with non-seminomatous germ cell tumours, 3 (0.5%) with
      stromal tumours, and 2 (0.3%) with other tumours. The median age was 32 years
      (range, 0-80 years). Preoperative marker levels were not available for 8% of
      patients, and initial staging was considered inadequate in 6%. Surveillance
      programs used for patients with Stage I disease were considered inadequate in
      most. Relative survival at five years was 99% for patients with seminoma and 91%
      for non-seminoma. CONCLUSIONS: There was considerable variation in the
      investigation, treatment, and follow-up of these patients, which is likely to
      have resulted in unnecessary morbidity. Clinical practice guidelines should be
      developed and implemented to promote optimal management.

PMID- 11346105
TI  - The efficacy of an antibiotic protocol for community-acquired pneumonia.
AB  - OBJECTIVE: To assess the efficacy of an antibiotic protocol to avoid empirical
      use of third-generation cephalosporins in community-acquired pneumonia (CAP).
      DESIGN AND SETTING: Retrospective case review of patients with CAP one year after
      implementing the protocol. Comparison was made with patients with CAP treated at
      a metropolitan tertiary referral hospital (where use of third-generation
      cephalosporins was common). PARTICIPANTS: 86 patients (district hospital with an
      antibiotic protocol) and 72 patients (metropolitan tertiary referral hospital),
      January - June 1999. OUTCOME MEASURES: Rate of staff adherence to the protocol;
      patient characteristics associated with poor protocol adherence; demographic and
      prognostic features of both groups at presentation; duration of intravenous
      therapy, time to defervescence, length of stay; inpatient mortality rates; and
      drug cost savings per patient treated according to the protocol. RESULTS: Overall
      protocol adherence rate was 60%. Patients with penicillin allergy were
      significantly less likely to receive treatment according to the protocol
      (P<0.001). At the district hospital, patients were generally older and taking
      more regular medications. Patients at each hospital had similar prognostic
      factors and demographic features at presentation. Inhospital mortality (P=0.92;
      95% CI, -0.08 to 0.07), duration of fever (P=0.57) and length of stay (P=0.78)
      were not significantly different between patients treated empirically with
      penicillin and those treated empirically with third-generation cephalosporins.
      Treating a patient according to the protocol saved an average of $77.44 in drug
      costs. CONCLUSION: One year after implementation, our protocol for treating CAP
      is proving efficacious, although levels of adherence could improve.

PMID- 11346106
TI  - Hepatitis A epidemiology in Australia: national seroprevalence and notifications.
AB  - OBJECTIVES: To determine hepatitis A seroprevalence and notification rates in
      Australia in order to inform vaccination policy. DESIGN: Seroprevalence was
      determined by cross-sectional survey of opportunistically collected sera;
      notifications were extracted from the National Notifiable Diseases Surveillance
      System. PARTICIPANTS: 3,043 serum samples collected in 1998 were obtained from 46
      laboratories around Australia. Sample size in each age group was based on
      expected seroprevalence, and States and Territories were sampled proportionally
      to their population size. Males and females were equally represented.
      Notifications were extracted for cases with onset between 1 January 1991 and 31
      December 1998. MAIN OUTCOME MEASURES: Seroprevalence and notifications were
      analysed by age, sex and State/Territory. RESULTS: 41.1% of serum samples were
      seropositive for hepatitis A (95% CI, 39.4%-42.9%) (population-weighted
      seroprevalence, 38.3%). Seroprevalence was significantly associated with
      increasing age (P<0.001), but did not differ between the sexes (male:female
      ratio, 1.04:1; 95% CI, 0.95-1.14). However, significantly more notifications were
      recorded for males than females (male:female ratio, 1.65:1; 95% CI, 1.60-1.70).
      The Northern Territory had the highest seroprevalence (68.8%; 95% CI, 52.7%
      84.8%) and annual notification rates (48.7 per 100,000 population; 95% CI, 45.0
      52.4 per 100,000). CONCLUSIONS: These data show that about half the Australian
      population has not been exposed to hepatitis A and is therefore susceptible to
      infection. However, any decision on national routine childhood hepatitis A
      vaccination requires a cost-benefit analysis. Routine vaccination of high
      incidence communities remains controversial.

PMID- 11346107
TI  - Should doctors wear white coats?
AB  - The wearing of white coats by hospital doctors is becoming a rarity, making it
      difficult for patients to identify doctors from other hospital staff. I asked
      patients with cancer whether they thought that doctors, both junior and senior,
      should wear white coats. Only a minority disapproved.

PMID- 11346108
TI  - Hospital gowns, white coats and infection control.

PMID- 11346109
TI  - EBM in practice: emergency medicine.
AB  - Multiple, synchronous and interdependent management questions in emergency
      medicine make it difficult to apply evidence-based medicine (EBM), which mostly
      focuses on single interventions. Emergency medicine is part of a system of care;
      EBM has limited utility in systems evaluation. There is a dearth of published
      evidence of specific relevance to emergency medicine. Because of practical
      difficulties with "real time" application of EBM in emergency medicine, methods
      have been adopted for incorporating evidence into practice in anticipation of
      clinical situations. Emergency medicine must improve its evidence base and
      develop methods suitable for evaluating systems of care.

PMID- 11346110
TI  - Ways of using evidence-based medicine in general practice.
AB  - General practitioners wanting to practise evidence-based medicine (EBM) are
      constrained by time factors and the great diversity of clinical problems they
      deal with. They need experience in knowing what questions to ask, in locating and
      evaluating the evidence, and in applying it. Conventional searching for the best
      evidence can be achieved in daily general practice. Sometimes the search can be
      performed during the consultation, but more often it can be done later and the
      patient can return for the "result". Case-based journal clubs provide a
      supportive environment for GPs to work together to find the best evidence at
      regular meetings. An evidence-based literature search service is being piloted to
      enhance decision-making for individual patients. A central facility provides the
      search and interprets the evidence in relation to individual cases. A request
      form and a "results" format make the service akin to pathology testing or
      imaging. Using EBM in general practice appears feasible. Major difficulties still
      exist before it can be practised by all GPs, but it has the potential to change
      the way doctors update their knowledge.

PMID- 11346111
TI  - Physician-assisted suicide in Oregon: why so few occurrences?
AB  - In the first three years that physician-assisted suicide (PAS) has been legal in
      Oregon, about two persons per month have taken medication to end their life. Most
      physicians are unwilling to prescribe the lethal medication. Because many
      terminally ill people are confined to their bed or home, the difficulty of
      finding a willing physician may have resulted in many abandoning the idea of
      using PAS. People living a long way from a large urban centre may be severely
      disadvantaged in their ability to obtain medication to end their lives.

PMID- 11346112
TI  - Fatal disseminated strongyloidiasis in a previously treated patient.

PMID- 11346113
TI  - 5: Movement disorders I: parkinsonism and the akinetic-rigid syndromes.
AB  - The major features of akinetic-rigid syndromes are bradykinesia (small, slow
      movements), rigidity and tremor, often summarised as "parkinsonism".
      Approximately 80% of akinetic-rigid syndromes are due to Parkinson's disease.
      Treatment of Parkinson's disease should be determined by level of disability and
      handicap. The combination of levodopa and peripheral dopadecarboxylase inhibitor
      is the most efficacious symptomatic treatment for Parkinson's disease. Motor
      fluctuations appear after 2-3 years of levodopa treatment, and affect at least
      50% of patients after five years. Surgery can relieve refractory tremor and
      dyskinesias, but does not alter disease progression or need for drug therapy.

PMID- 11346114
TI  - The Helicobacter hypothesis.

PMID- 11346115
TI  - Azithromycin and pelvic inflammatory disease in the Northern Territory.

PMID- 11346116
TI  - COX-2 inhibitors.

PMID- 11346117
TI  - COX-2 inhibitors.

PMID- 11346118
TI  - COX-2 inhibitors.

PMID- 11346119
TI  - The medical emergency team.

PMID- 11346120
TI  - The medical emergency team.

PMID- 11346121
TI  - The medical emergency team.

PMID- 11346122
TI  - Modifying academic ranking of rural and remote medical school applicants.

PMID- 11346123
TI  - Harnessing the intellectual wealth of Australia.

PMID- 11346124
TI  - Dry eye in the elderly.
AB  - Dry eye in the elderly population is a condition with a multitude of contributing
      factors and a wide spectrum of severity. The complex tear film is made up of
      layers of oil, aqueous and mucin, produced by the meibomian glands, main and
      accessory lacrimal glands, and by the goblet cells, respectively. Alteration in
      the normal function of any of these structures by disease, trauma or the
      environment can cause dysfunction of the tear film and result in the symptoms of
      dry eye (such as burning, grittiness and blurred vision). Normal lid anatomy and
      closure is critical to prevent evaporation of the normal tear film. The mainstay
      of current therapy is augmentation of the tear film with artificial tears and
      ointment. More severe cases of dry eye may require occlusion of the tear drainage
      system with plugs or electrocautery scarring. Good lid hygiene is also important
      for tear film health. A new paradigm of dry eye as a subclinical inflammatory
      disease has recently been suggested, and preliminary results from treatment with
      topical cyclosporin formulations are encouraging. The next few years promise
      exciting advances and relief for patients suffering from this chronic condition.

PMID- 11346125
TI  - Contemporary management of chronic stable angina.
AB  - Chronic stable angina is a common condition with a prognosis that is less benign
      than is generally appreciated. The optimal treatment strategy of this disorder is
      unclear, and few anti-ischaemic agents have been rigorously tested in
      prospectively randomised mortality studies. The evidence base for the anti
      ischaemic therapy of chronic angina draws upon data 'borrowed' from studies in
      acute coronary syndromes, and from studies in chronic angina using surrogate
      endpoints such as ambulatory silent ischaemia. Such evidence leads us to believe
      that anti-ischaemic therapy with beta-blockers offers a mortality benefit in
      chronic angina. In contrast, the mortality benefit of lipid lowering therapy and
      antiplatelet agents is well proven. Angioplasty offers no mortality benefit in
      the treatment of chronic angina, although it is more effective than medical
      therapy alone for the relief of symptoms. In a few patients with high order
      proximal coronary disease, coronary bypass surgery offers a distinct mortality
      advantage compared with medical treatment alone. Most patients, however, do not
      warrant such an approach, and only require surgery for when they remain
      symptomatic despite adequate medical therapy. Alternative strategies such as
      cardiac transplantation, transmyocardial laser revascularisation and spinal cord
      stimulation are now accepted in a subgroup of patients for the treatment of
      chronic angina refractory to standard therapy.

PMID- 11346126
TI  - Epidemiology of over-the-counter drug use in community dwelling elderly: United
      States perspective.
AB  - Among US community dwelling individuals aged > or = 65 years, about as many
      persons take nonprescription drugs as take prescription drugs. A review of US
      data from the last 2 decades indicates that the average number of over-the
      counter (OTC) drugs taken daily is around 1.8, but varies with geographical area
      (highest in the Midwest) and race/ethnicity (lowest use among Hispanics, followed
      by African Americans. and highest use among Whites). Use has consistently been
      found to be higher in women than in men. While OTC use appears to be increasing
      over time, it also decreases with increase in age. The most common OTC classes
      used are analgesics, laxatives and nutritional supplements. Our ability to
      explain or to predict OTC use and change in use is poor, and further studies,
      particularly on use by elderly individuals of minority races, are needed.

PMID- 11346127
TI  - Status epilepticus in older patients: epidemiology and treatment options.
AB  - Status epilepticus (SE) is a medical and neurological emergency that has been
      associated with significant morbidity and mortality. The most widely accepted
      definition of SE is more than 30 minutes of either continuous seizure activity,
      or intermittent seizures without full recovery of consciousness between seizures.
      SE is a major clinical concern in the elderly population, both because it has
      increased incidence in the elderly compared with the general population, and
      because of concurrent medical conditions that are more likely to complicate
      therapy and worsen prognosis in elderly individuals. The incidence of SE in the
      elderly is almost twice that of the general population at 86 per 100,000 per
      year. With the anticipated growth of the elderly population, SE is likely to
      become an increasingly common problem facing clinicians, and an important public
      health issue. The elderly have the highest SE-associated mortality of any age
      group at 38%, and the very old elderly (>80 years of age) have a mortality of at
      least 50%. Acute or remote stroke is the most common aetiology of SE in the
      elderly. Nonconvulsive SE (NCSE) has a wide range of clinical presentations,
      ranging from confusion to obtundation. It occurs commonly in elderly patients who
      are critically ill and in the setting of coma. Electroencephalogram is the only
      reliable method of diagnosing NCSE. The goal of treatment for SE is rapid
      cessation of clinical and electrical seizure activity. Most treatment protocols
      call for the immediate administration of an intravenous benzodiazepine, followed
      by phenytoin or fosphenytoin. Recent studies suggest that when this initial
      treatment of SE fails, little is gained by using additional standard drugs.
      General anaesthetic agents (such as pentobarbital, midazolam, or propofol) should
      be expeditiously employed, although these treatments have their own potential
      complications. Intravenous valproic acid is a recent addition to the
      armamentarium of drugs for the treatment of SE, with a low risk of hypotension,
      respiratory depression and hypotension, making it a potentially useful drug for
      the treatment of SE in the elderly. However, further information is needed to
      establish its role in the overall treatment of SE.

PMID- 11346128
TI  - Is it possible to reduce polypharmacy in the elderly? A randomised, controlled
      trial.
AB  - OBJECTIVE: The present trial was originally designed to investigate the
      effectiveness of comprehensive day hospital care in chronically ill elderly
      patients. Another aim, reported here, was to investigate to what extent it is
      possible to reduce polypharmacy and simplify drug regimens during the short term
      tight control conditions of day hospital care. PATIENTS: All home care patients
      (n = 174, mean age 77 years) in a rural area, Kirkkonummi-Siuntio, in Finland.
      DESIGN AND SETTING: Patients were randomised into 2 groups, one of which was
      offered a 2-month period of day hospital care. Patients assumed to be
      noncompliant (because they did not want day hospital care) were also included in
      order to see the effect of intervention in 'real-life'. The medications of all
      participants were reviewed and counted during an in-home assessment by a home
      nurse. In the intervention group, necessary revisions (dose reduction,
      discontinuation, possible additions) were performed through the tight monitoring
      of day hospital care and in co-operation with the patient. The patients were
      followed up for 10 months after completion of the intervention programme. OUTCOME
      MEASURES: Number of prescribed medications, number of over-the-counter (OTC)
      drugs, number of doses taken daily by the patients. Assessments were performed at
      baseline, and after 2, 5 and 12 months. RESULTS: There were no significant
      changes in the number of prescribed medications. In patients in day hospital
      care, the number of doses was reduced significantly (p = 0.02) during the 2-month
      day hospital period compared with the control group. However, the patients
      compensated for the reductions by increasing the use of OTC drugs during the day
      hospital period (p = 0.05). In addition, only 3 months after the trial, the
      number of drugs had already returned to the baseline level. CONCLUSIONS: In real
      life it seems to be difficult to reduce polypharmacy in the elderly. Some drug
      reductions may be achieved with tight control under trial conditions, but when
      the intervention ceases the number of drugs used soon returns to its earlier
      level.

PMID- 11346129
TI  - Optimising treatment for resectable rectal cancer: is preoperative therapy
      beneficial?
AB  - Preoperative radiotherapy is becoming the standard of care for resectable locally
      advanced adenocarcinoma of the rectum. Its practice is no longer limited to a few
      specialised cancer centres. Adjuvant preoperative radiotherapy can reduce the
      risk of local recurrence by 50% compared with surgery alone and it has a moderate
      effect in improving survival. Treatment-related toxicity is superior to that
      after postoperative radiotherapy. Early results of preoperative radiotherapy with
      concurrent chemotherapy are promising, with a low toxicity profile and a high
      pathological response rate. Advances in technology, endorectal ultrasound and
      magnetic resonance imaging enable selection of appropriate patients for
      preoperative radiotherapy.

PMID- 11346130
TI  - The clinical potential of matrix metalloproteinase inhibitors in the rheumatic
      disorders.
AB  - Rheumatoid arthritis (RA) and osteoarthritis are chronic diseases that result in
      cartilage degradation and loss of joint function. Currently available drugs are
      predominantly directed towards the control of pain and/or the inflammation
      associated with joint synovitis but they do little to reduce joint destruction.
      In the future, it will be important to have drugs that prevent the structural
      damage caused by bone and cartilage breakdown. In this review, we will outline
      the structure and function of cartilage and the key features of matrix
      metalloproteinases (MMPs), enzymes involved in joint destruction. We will present
      evidence for the role of MMPs in RA and osteoarthritis, and describe the
      potential of synthetic inhibitors to control MMP activity and so prevent joint
      destruction. MMPs are able to cleave all components of the cartilage matrix.
      Regulation of MMPs is aberrant in osteoarthritis and RA, and MMPs have been
      implicated in the collagen breakdown that contributes to joint destruction in
      these diseases. Synthetic MMP inhibitors have been developed. In animal models of
      osteoarthritis and/or RA, these agents have shown chondroprotective effects.
      However, results from clinical trials in RA have been equivocal, with some
      studies being terminated because of lack of efficacy or safety concerns.
      Nevertheless, this approach remains promising. Increased understanding of the
      structure, regulation and function of individual MMPs may lead to more effective
      strategies, and approaches aimed at multiple steps of the pathogenesis of
      arthritis may be needed to break the chronic cycle of joint destruction.

PMID- 11346131
TI  - Intake of dioxins and related compounds from food in the U.S. population.
AB  - The first U.S. nationwide food sampling with measurement of dioxins,
      dibenzofurans, and coplanar, mono-ortho and di-ortho polychlorinated biphenyls
      (PCBs) is reported in this study. Twelve separate analyses were conducted on 110
      food samples divided into pooled lots by category. The samples were purchased in
      1995 in supermarkets in Atlanta, GA, Binghamton, NY, Chicago, IL, Louisville, KY,
      and San Diego, CA. Human milk also was collected to estimate nursing infants'
      consumption. The food category with highest World Health Organization (WHO)
      dioxin toxic equivalent (TEQ) concentration was farm-grown freshwater fish fillet
      with 1.7 pg/g, or parts per trillion (ppt), wet, or whole, weight. The category
      with the lowest TEQ level was a simulated vegandiet, with 0.09 ppt. TEQ
      concentrations in ocean fish, beef, chicken, pork, sandwich meat, eggs, cheese,
      and ice cream, as well as human milk, were in the range O.33 to 0.51 ppt, wet
      weight. In whole dairy milk TEQ was 0.16 ppt, and in butter 1.1 ppt. Mean daily
      intake of TEQ for U.S. breast-fed infants during the first year of life was
      estimated at 42 pg/kg body weight. For children aged 1-11 yr the estimated daily
      TEQ intake was 6.2 pg/kg body weight. For males and females aged 12-19 yr, the
      estimated TEQ intake was 3.5 and 2.7 pg/kg body weight, respectively. For adult
      men and women aged 20-79 yr, estimated mean daily TEQ intakes were 2.4 and 2.2
      pg/kg body weight, respectively. Estimated mean daily intake of TEQ declined with
      age to a low of 1.9 pg/kg body weight at age 80 yr and older. For all ages except
      80 yr and over, estimates were higher for males than females. For adults,
      dioxins, dibenzofurans, and PCBs contributed 42%, 30%, and 28% of dietary TEQ
      intake, respectively. DDE was also analyzed in the pooled food samples.

PMID- 11346132
TI  - Analysis of methylmercury disposition in humans utilizing a PBPK model and animal
      pharmacokinetic data.
AB  - Physiologically based pharmacokinetic (PBPK) models are excellent tools to aid in
      the extrapolation of animal data to humans. When the fate of the chemical is the
      same among species being compared, animal data can appropriately be considered as
      a model for human exposure. For methylmercury exposure, sufficient data exist to
      allow comparison of numerous mammalian species to humans. PBPK model validation
      entails obtaining blood and tissue concentrations of the parent chemical and
      metabolite(s) at various times following a known exposure. From ethical and
      practical considerations, human tissue concentrations following a known exposure
      to an environmental toxicant are scarce. While animal-to-human extrapolation
      demands that sufficient human data exist to validate the model, the validation
      requirements are less stringent if multiple animal models are utilized within a
      single model template. A versatile PBPK model was used to analyze the
      distribution and elimination of methylmercury and its metabolite, inorganic
      mercury. Uniquely, the model is formed in a generic way from a single basic
      template during the initial program compilation. Basic parameters are defined for
      diffferent PBPK models for mammalian species that span a relatively large range
      of sizes. In this article, the analyses include 12 species (mouse, hamster, rat,
      guinea pig, cat, rabbit, monkey, sheep, pig, goat, cow, and human). Allometric
      (weight-based) correlations of tissue binding coefficients, metabolism rate
      constants, and elimination parameters for both methylmercury and inorganic
      mercury are presented for species for which sufficient data are available. The
      resulting human model, in accord with the animal models, predicts relatively high
      inorganic mercury levels in the kidneys long after the disappearance of
      methylmercury from the blood.

PMID- 11346133
TI  - Exposure to flaxseed and its purified lignan reduces bone strength in young but
      not older male rats.
AB  - Flaxseed is the richest source of the plant lignan secoisolariciresinol
      diglycoside (SDG), which is converted to the two major mammalian lignans,
      enterodiol (ED) and enterolactone (EL), by colonic bacteria. Because both ED and
      EL can produce biological effects similar to estrogen, exposure to lignans during
      early stages of development may adversely alter the normal development of bone in
      males since bone is a hormone-sensitive tissue. To determine whether early
      exposure to flaxseed or its lignan compromised the acquisition of bone mass or
      reduced bone strength, male offspring were exposed to one of three diets during
      lactation only (birth through postnatal day [PND] 21) via mother's milk or
      continuously from the start of lactation through to adolescence (PND 50) or young
      adulthood (PND 132). The diets were a basal diet (BD) that was devoid of
      phytoestrogens, BD containing 10% flaxseed, or BD containing the equivalent
      quantity of SDG present in a 10% flaxseed diet. To assess bone quantity, the bone
      mineral content (BMC) and bone mineral density (BMD) of femurs were assessed by
      dual-energy x-ray absorptiometry. Since the biomechanical properties of bone are
      indicators of the microarchitecture and thus bone quality, the biomechanical
      strength of femurs was assessed by three-point bending. At PND 50, ultimate
      bending stress and Young's modulus, measures of bone strength, were reduced among
      rats that received the 10% flaxseed diet from PND 0 through PND 50, while there
      were no marked differences in bone size, BMC, or BMD among groups. Interestingly,
      this effect does not appear to be due to the lignan in flaxseed, as continuous
      exposure to the diet containing the equivalent quantity of lignan (10 S diet) did
      not alter any measures of bone strength. In contrast to PND 50, bone strength did
      not differ among groups at PND 132, indicating that the compromise in bone
      strength was not sustained into early adulthood. Bone size, BMC, and BMD
      continued to be similar among treatment groups at PND 132. In conclusion,
      exposing male rats to a diet containing 10% flaxseed or an equivalent quantity of
      lignan either during lactation only or through to early adulthood is safe with
      respect to bone health, as measures of bone mass and strength were similar to
      control rats.

PMID- 11346134
TI  - Effects of chronic sodium azide on brain and muscle cytochrome oxidase activity:
      a potential model to investigate environmental contributions to neurodegenerative
      diseases.
AB  - Deficits in oxidative phosphorylation have been implicated in many
      neurodegenerative diseases. In this study, cytochrome oxidase activity was
      inhibited following a 28-d systemic administration of nonlethal sodium azide via
      subcutaneous osmotic pumps. Quantitative enzyme histochemistry was performed on
      tissue sections from brain, skeletal muscle, and heart to localize cytochrome
      oxidase activity both globally and in regions within each tissue. Significant
      decreases of cytochrome oxidase activity were found in the brain and skeletal
      muscle but not heart. In addition, regions within each tissue were also analyzed,
      such as cortex and striatum in the brain and red and white fibers in skeletal
      muscle. The tissue specific inhibition of cytochrome oxidase by sodium azide
      could serve as a positive control for studies of other mitochondrial toxins in
      aerobically compromised cells. Therefore, chronic nonlethal sodium azide
      administration may provide a potential rat model for the study of mitochondrial
      dysfunction and the role of environmental pollutants in brain and muscle tissues
      affected in certain neurodegenerative diseases.

PMID- 11346135
TI  - Hepatocellular carcinoma: global epidemiology.

PMID- 11346136
TI  - Japanese approach to hepatocellular carcinoma.

PMID- 11346137
TI  - Inhibition of cholesterol absorption by alpha-olefin maleic acid.

PMID- 11346138
TI  - Bile duct cell apoptosis: a rare event in primary biliary cirrhosis?

PMID- 11346139
TI  - Ranitidine bismuth citrate or omeprazole-based triple therapy for Helicobacter
      pylori eradication in Helicobacter pylori-infected non-ulcer dyspepsia.
AB  - AIM: To test the eradication rate of Helicobacter pylori by ranitidine bismuth
      citrate-based triple therapy, and evaluate the symptomatic response of
      Helicobacter pylori eradication therapy for non-ulcer dyspepsia. METHODS: A total
      of 59 consecutive Helicobacter pylori infected non-ulcer dyspepsia patients were
      randomly selected to receive either one of two triple therapy regimens, including
      metronidazole, amoxycillin plus ranitidine bismuth citrate (RAM group) or
      omeprazole (OAM group). To determine the success of eradication, patients
      underwent the 13C-urea breath test, 6 weeks and one year after treatment. The
      dyspeptic symptom scores were also assessed at the time of enrolment, 6 weeks and
      one year after treatment. RESULTS: Per-protocol and intention-to-treat
      eradication rates were 77.7% and 70% in RAM group and 83.8% and 68.9% in OAM
      group (p = non significant). At both the 6th week and at the first year after
      treatment, the mean symptom scores were lower than pre-treatment scores in the
      study population, regardless of whether treatment was successful or not. However,
      patients, whether eradicated successfully or not-eradicated, presented similar 6
      week and 1-year scores. CONCLUSIONS: One-week RAM triple therapy, which is
      cheaper than the OAM regimen, is a relatively effective alternative regimen for
      Helicobacter pylori eradication in Taiwanese. Triple therapy for Helicobacter
      pylori eradication was not the whole management for the relief of dyspeptic
      symptoms of non-ulcer dyspepsia patients.

PMID- 11346140
TI  - Randomised study of the efficacy of omeprazole and clarithromycin with either
      amoxycillin or metronidazole in the eradication of Helicobacter pylori in
      screened primary care patients.
AB  - BACKGROUND: Population Helicobacter pylori screening and treatment has been
      advocated as a means of reducing mortality from gastric cancer. The optimum
      Helicobacter pylori eradication therapy to use in this setting is uncertain.
      AIMS: To compare efficacy of seven days of omeprazole, clarithromycin and either
      metronidazole, or amoxycillin in Helicobacter pylori positive subjects detected
      by population screening. PATIENTS: Helicobacter pylori positive patients from the
      placebo group of a population screening and treatment trial were invited to take
      part in the investigation. METHODS: Patients were randomised to receive either
      omeprazole, clarithromycin and metronidazole or omeprazole, clarithromycin and
      amoxycillin, and Helicobacter pylori eradication was verified with a 13C-urea
      breath test at least four weeks after completion of therapy. RESULTS: A total of
      221 patients took part in the study and 210 completed the protocol. Treatment was
      successful in 93/111 [84%) patients allocated to omeprazole, clarithromycin and
      metronidazole and in 96/110 (87%) allocated to omeprazole, clarithromycin and
      amoxycillin in an intention-to-treat analysis (p=0.46). Per protocol eradication
      rates were 93/107 (87%) in the metronidazole, and 96/103 (93%) amoxycillin group
      (p=0.129). CONCLUSIONS: There was no significant difference between the two
      regimens. The eradication rates achieved are comparable with previous studies in
      both dyspepsia and peptic ulcer patients.

PMID- 11346141
TI  - Effect of zinc supplementation on trace elements and intestinal metallothionein
      concentrations in experimental colitis in the rat.
AB  - BACKGROUND AND AIM: Zinc enhances cell protection against infection and injury
      and the healing processes themselves. We evaluated the effect of zinc
      supplementation at different doses on a model of experimental colitis in the rat.
      METHODS: Colitis, induced by intra-rectal instillation of dinitrobenzen-sulphonic
      acid, was assessed at 1 week by examining: general outcome and macroscopic
      damage, myeloperoxidase activity, mucosal zinc, iron and metallothionein
      concentrations. Rats received zinc sulphate, 2 mg/kg or 30 mg/kg, twice a day by
      gavage for 9 days, starting 3 days before the induction of colitis, or
      intrarectal instillation of zinc (20 mg/kg) once daily starting 8 hours after the
      induction of colitis and for 6 days thereafter RESULTS: Zinc-treated rats had
      less diarrhoea, higher body weight and lower colonic weight than untreated rats
      but no effect was observed on macroscopic inflammation, adhesions, colonic
      distension and neutrophil infiltration of the colonic mucosa. Zinc
      supplementation did not affect mucosal iron and zinc concentrations or plasma
      zinc levels in colitic rats. Metallothionein synthesis was induced in control
      rats and to a lesser extent in colitic rats. CONCLUSION: Zinc administration
      induces metallothionein synthesis but has little effect on the short-term course
      of experimental colitis.

PMID- 11346142
TI  - Recurrent abdominal pain and consulting behaviour among children in a rural
      community in Malaysia.
AB  - AIM: To look at predictors of consulting behaviour among children with recurrent
      abdominal pain in a rural community in Malaysia. SUBJECTS AND METHODS: A sample
      of 1462 school-children aged between 9 and 15 years were randomly selected from
      all schools in Kuala Langat, a rural district in Malaysia. Those with recurrent
      abdominal pain, defined according to Apley's criteria, were recruited and divided
      into consulters and non-consulters. A consulter was defined as a child who had
      sought the help of a medical practitioner at least once in the past year for
      recurrent abdominal pain. A detailed clinical, social and family history was
      obtained in all recruited children. RESULTS: A total of 161 children were
      recruited: 78 (48.4%) consulters, 83 (51.6%) non-consulters. Of the consulters,
      40 were boys, 38 were girls (male:female ratio = 1.1:1). The two sexes did not
      show a significant difference in prevalence of consulters [p=0.189). Of the
      ethnic groups, only Indians had a significantly higher likelihood to consult a
      doctor (Indians, p=0.006; Malays, p=0.742; Chinese, p=0.050]. Younger children
      (under 12 years) had a significantly higher chance of having been brought to see
      a medical practitioner (p=0.014). Children in whom age of onset of abdominal pain
      was below ten years were also more likely to have been seen by a doctor
      (p=0.012). Children who had consulted a doctor were more likely to be missing
      school because of abdominal pain (p<0.001). Pain severity was not a significant
      factor (p=0.429). Multiple logistic regression analysis revealed that the only
      variable that remained significantly associated with health-care consultation was
      school absence (p<0.001). CONCLUSIONS: Children who saw their doctors for
      recurrent abdominal pain were also more likely to be those who missed school on
      account of abdominal pain. Following multiple regression analysis, other factors
      were no longer significant.

PMID- 11346143
TI  - Inhibition of intestinal cholesterol absorption by surfomer (alpha-olefin maleic
      acid) affects hepatic cholesterol synthesis and low density lipoprotein transport
      in hamsters fed a fat-enriched diet.
AB  - BACKGROUND: Surfomer (alpha-olefin maleic acid) reduces intestinal cholesterol
      absorption. AIMS: This study was performed to investigate the effect of surfomer
      on cholesterol synthesis and low density lipoprotein in hamsters fed a
      hypercholesterolaemic, lipid-enriched diet. ANIMALS AND METHODS: Male hamsters
      were fed a diet enriched in cholesterol (0.07%) and saturated fatty acids
      (coconut oil 20%); the diet was supplemented with 3% surfomer, for 1-4 weeks.
      Cholesterol synthesis was assessed measuring incorporation of [3H]water into
      tissue sterols; low density lipoprotein clearance was determined using a primed
      continuous infusion of (125I)tyramine-cellobiose lipoprotein. RESULTS:
      Cholesterol synthesis was suppressed after 3 weeks of hyperlipidaemic diet in
      liver and small bowel (by 88% and 38%, respectively) and was significantly
      increased by supplementing the fat-enriched diet with surfomer. Low density
      lipoprotein-cholesterol was increased by 44% after 4 weeks of hyperlipidaemic
      diet, in parallel with a decrease in hepatic low density lipoprotein clearance
      rates (48+/-3 vs 68+/-7 microl of plasma/h per g of tissue). Concurrent treatment
      with surfomer for 1, 2 or 4 weeks prevented the decrease of clearance and
      maintained normal low density lipoprotein-cholesterol levels at all time points.
      CONCLUSIONS: Surfomer represents a powerful tool to investigate the impact of
      cholesterol absorption on sterol homeostasis. Furthermore, since surfomer appears
      to normalize low density lipoprotein transport in hamsters fed a diet comparable
      to a lipid-rich "western-style" regimen, this drug may deserve consideration as
      an adjunct treatment for hypercholesterolaemia in selected patient groups.

PMID- 11346144
TI  - Bile duct cell apoptosis is a rare event in primary biliary cirrhosis.
AB  - BACKGROUND: The frequency of apoptosis in bile duct cells of primary biliary
      cirrhosis is still unclear spanning from rare to 50% in the various reports. AIM:
      To study bile duct cell apoptosis in stage I primary biliary cirrhosis lesions.
      PATIENTS: Nine stage I-II biopsies with a total number of 26 bile ducts of
      different sizes, selected from a larger series on the basis of the expression on
      serial frozen sections of HLA-DR and Fas antigens. METHODS: Apoptosis was
      evaluated by a DNA fragmentation assay on frozen sections, according to the
      manufacturer's protocol and by expression of apoptosis related cytokeratin
      neoepitopes. Bile duct cell proliferation was assessed by MIB1 (Ki-67)
      expression. RESULTS: Apoptosis was frequently found in inflammatory cells of
      portal tracts and sinusoids. Apoptosis of hepatocytes was also systematically
      observed. Only 4 positive bile duct cells were found in 3 bile ducts from 3
      biopsies. Quantitative evaluation was not attempted. Cholangiocyte proliferation
      was observed in the same ducts and occasionally in other biopsies. CONCLUSIONS:
      These data suggest that cholangiocyte death by apoptosis at the level of typical
      primary biliary cirrhosis lesions is a rare event, at least in early stages of
      the disease. The observed rate of proliferation was consistent with the rate of
      apoptosis.

PMID- 11346145
TI  - Chronic hepatitis C treated with phlebotomy alone: biochemical and histological
      outcome.
AB  - BACKGROUND: In patients with chronic hepatitis C, the histological outcome of
      long term phlebotomy is unknown. AIM: To investigate biochemical and histological
      findings before and after phlebotomy in chronic hepatitis C. PATIENTS: Twenty
      four non-haemochromatotic patients with chronic hepatitis C were treated with
      long-term phlebotomy alone. RESULTS: Hepatic iron concentration had decreased in
      all patients who underwent a second liver biopsy, two years after iron depletion
      was attained and maintained. Histological grading score decreased in four
      patients, was unchanged in two, and increased in five. Histological staging score
      decreased in two patients, was unchanged in five, and increased in four.
      Pretreatment high serum selenium level predicted the reduction of the
      inflammatory grading score in univariate analysis (p=0.008, while low serum
      aspartate aminotransferase (p=0.02) and low propeptide of procollagen III
      (p=0.08) levels predicted the lack of progression of liver fibrosis. Furthermore,
      when iron depletion was reached, significant reductions of serum levels of
      aminotransferase, gamma glutamyl transferase (-47%), propeptide of procollagen
      III, alpha foetoprotein, selenium were observed in 24 patients. No changes in
      serum hepatitis C virus-RNA levels were found. CONCLUSIONS: Phlebotomy alone
      seems to be efficacious in suppressing progression of chronic hepatitis C in some
      patients. Phlebotomy not only induces iron depletion, but it even modifies serum
      levels of other trace elements involved in the balance between oxidant and
      antioxidant processes.

PMID- 11346146
TI  - Pilot dose-finding trial on interferon alpha in combination with ribavirin for
      the treatment of chronic hepatitis C in patients not responding to interferon
      alone.
AB  - BACKGROUND: Effectiveness of combination therapy with standard interferon alpha
      doses and ribavirin is far from being demonstrated in patients with hepatitis C
      non responders to interferon alpha monotherapy. Recent kinetic studies revealed
      that these doses may be suboptimal. AIMS: To find the criteria for optimisation
      of the interferon dose, to be used in combination with ribavirin in patients with
      hepatitis C non responders to interferon alpha monotherapy. PATIENTS: Sixty-three
      patients enrolled in a pilot controlled trial were treated for 6 months with
      ribavirin ([1000-1200 mg daily) and were randomised to concurrently receive
      interferon alpha 2b for 6 months at: 3 Million Units thrice weekly [group A (21
      patients)], 5 MU thrice weekly [group B (21 patients)] and 5 million units daily
      [group C (21 patients)]. RESULTS: A sustained virological response was observed
      in: 1 patient from group A (5%), 2 patients from group B (9%) and 8 patients from
      group C (38%; p=0.02 vs group A; p=0.03 vs group B). Side-effects were not
      significantly different between the 3 groups. Multivariate analysis showed that
      infection by hepatitis C virus genotypes 2 or 3 and interferon alpha dosage of 5
      million units daily were independent predictors of sustained response.
      CONCLUSIONS: These results suggest that higher interferon doses administered
      daily in combination with ribavirin could be more effective in those patients
      with hepatitis C who had not responded to interferon alone.

PMID- 11346147
TI  - Mammalian augmenter of liver regeneration protein is a sulfhydryl oxidase.
AB  - BACKGROUND: Augmenter of Liver Regeneration is an important secondary hepatic
      growth factor. Augmenter of liver regeneration protein has been shown to control
      mitochondrial gene expression and the lytic activity of liver-resident Natural
      Killer cells through the levels of interferon-gamma, but the precise enzymatic
      function of this protein is unknown. AIMS: To define the enzymatic activity of
      augmenter of liver regeneration protein. The carboxy terminus of augmenter of
      liver regeneration protein contains a special CXXC motif characteristic for redox
      proteins and with faint homologies to the redox-active site of sulfhydryl
      oxidases. Tests were, therefore, carried out to establish whether isolated
      augmenter of liver regeneration protein can also function in the formation of
      sulfur bridges. METHODS: Purified augmenter of liver regeneration proteins from
      rat and human were tested in enzyme assays for the ability to introduce disulfide
      bonds into protein substrates. The isolated proteins were tested for the
      formation of dimers and the presence of bound FAD was investigated
      spectroscopically. The function of the conserved CXXC motif was investigated by
      in vitro mutagenesis experiments and subsequent enzyme assays. RESULTS: In this
      study, we demonstrate that rat and human augmenter of liver regeneration protein
      are flavin-linked sulfhydryl oxidases that catalyze the formation of disulfide
      bonds in reduced protein substrates. A flavin moiety is firmly but not covalently
      attached to the protein. In human cell cultures augmenter of liver regeneration
      protein is expressed in a long and short form that both exist as covalently
      linked dimers. The active site of the enzyme is associated with a conserved CXXC
      motif in the carboxy-terminal domain, that is present in the homologous proteins
      from yeast to humans and also in the human Q6 growth regulator protein. In vitro
      mutagenesis of one cysteine residue in the CXXC motif results in loss of
      enzymatic function and the mutated protein no longer binds FAD. CONCLUSIONS: For
      the first time, these data assign an enzymatic activity to the important hepatic
      growth factor augmenter of liver regeneration protein. The finding that augmenter
      of liver regeneration protein acts as a FAD-linked sulfhydryl oxidase is
      essential to identify the molecular targets inside liver cells and to elucidate
      the precise role of mammalian augmenter of liver regeneration protein in hepatic
      cell growth, liver disease and regeneration.

PMID- 11346148
TI  - Impact of Celsior solution on hepatocellular, reperfusion and endothelial cell
      injury after liver transplantation.
AB  - BACKGROUND: Initially, preservation solutions were developed to maintain cell
      function of the transplanted organs. However, recently developed preservation
      solutions also contain a variety of substances to reduce the reperfusion injury.
      AIM: To study the effect of three different preservation solutions on the liver
      cell injury, endothelial cell function and reperfusion injury after liver
      transplantation. MATERIAL AND METHODS: Large White X Landrace pigs of either sex
      were subjected to orthotopic liver transplantation. Donor livers were flushed and
      stored in University of Wisconsin Solution, Eurocollins Solution or Celsior
      Solution for 3 hours. Blood samples were taken at various times post
      transplantation for assessment of aspartate aminotransferase, hyaluronic acid,
      malondialdehyde and Vitamin A levels. RESULTS: Serum aspartate aminotransferase
      levels were lower in the livers preserved in the Wisconsin solution. Plasma
      malondialdehyde levels were lower and serum Vitamin A levels were higher in the
      livers preserved in Celsior solution. Serum hyaluronic acid levels increased
      after liver transplantation but were similar with all three solutions.
      CONCLUSIONS: There was less hepato-cellular injury in the livers preserved in
      Wisconsin solution and less reperfusion injury with the Celsior solution. The
      endothelial cell injury was similar with all three solutions.

PMID- 11346149
TI  - Lateral pancreatojejunostomy in the surgical management of chronic pancreatitis.
      Current concepts and future perspectives.
AB  - Chronic pancreatitis is a medical disease, but surgery will be required for a
      selected subgroup of patients. Main indications for surgery in chronic
      pancreatitis are severe truly incapacitating pain refractory to medical therapy,
      local complications of pancreatitis or suspicion of malignancy. Surgical options
      include resective and drainage procedures. The choice of operation depends on the
      structural anatomy of the gland and the adjacent organs. Lateral
      pancreatojejunostomy is the preferred drainage procedure, because it is safe and
      effective in relieving the pain, while it preserves whatever pre-surgical
      pancreatic endocrine/exocrine function exists. It is indicated in large duct
      chronic pancreatitis (diameter of the main pancreatic duct >7 mm]; however,
      recently there is an increased interest in defining its role in small duct
      disease. The main advantage of the lateral pancreatojejunostomy over the
      resectional procedures is the preservation of the pancreatic parenchyma and
      endocrine and exocrine pancreatic function and the significantly lower early and
      late morbidity and mortality

PMID- 11346150
TI  - Somatostatin and octreotide in acute pancreatitis: the never-ending story.
AB  - The role of somatostatin and octreotide in the treatment of acute pancreatitis
      has been studied in the last two decades. We describe the physiologic activities
      of somatostatin and octreotide and their action on pancreas secretion. Results of
      experimental studies on the action of somatostatin and octreotide in some models
      of acute pancreatitis are discussed as well as the results of clinical studies on
      the effects of the two drugs in human acute pancreatitis. On the basis of these
      data, we suggest that somatostatin and octreotide should not be recommended for
      the prevention and treatment of acute pancreatitis.

PMID- 11346151
TI  - Persistently normal aminotransferase in chronic hepatitis C virus infection: is
      it time to redefine parameters of "normality"?

PMID- 11346152
TI  - Current management of hepatitis C in New Zealand.

PMID- 11346153
TI  - Interferon-alpha2a/ribaviran versus interferon-alpha2a alone for the retreatment
      of hepatitis C patients who relapse after a standard course of interferon.
AB  - AIM: To compare the efficacy of a descalating dose of interferon (48 weeks)
      versus a combination therapy of interferon and ribavirin (24 weeks) in hepatitis
      C positive subjects who relapsed within six months of cessation of a standard six
      month course of interferon three million units thrice weekly. METHODS: All 32
      subjects had biopsy proven chronic hepatitis C, were PCR positive and had
      elevated transaminase enzymes at least one and a half times the upper limit of
      normal. Subjects were randomly assigned to either a descalating dose of
      interferon-alpha-2a; six million units thrice weekly for 24 weeks followed by 3
      MIU 3x for 24 weeks or interferon three million units thrice weekly for 24 weeks
      plus ribavirin 1,000 mg/day for 12 weeks. A complete virological response was
      defined as a negative PCR for HCV RNA at 24 weeks after cessation of therapy.
      RESULTS: Sixteen patients were assigned to each arm and the sustained virological
      response was 50% for both the interferon and combination therapy arm (pNS). The
      biochemical response correlated with the virological response; 7/8 virological
      responders in the interferon alone had normalisation of transaminase 24 weeks
      post treatment as did 8/8 of those in the combination arm. One patient withdrew
      from treatment in the descalating interferon group and three required dose
      reduction. No subjects in the combination arm discontinued therapy but dose
      reduction was required in three subjects. CONCLUSION: High dose descalating
      interferon-alpha 2a and a combination of interferon-alpha 2a and ribavirin were
      effective in achieving a sustained virological response in 50% of subjects who
      had relapsed after a standard six month course of interferon.

PMID- 11346154
TI  - Hepatitis services at an injecting drug user outreach clinic.
AB  - AIMS: To provide a culturally appropriate, accessible and affordable hepatitis
      outreach clinic for injecting drug users, a traditionally hard-to-reach
      population. METHODS: The community-based clinic, a collaborative project between
      the Wellington Drugs and Health Development Project and Capital Coast Health, was
      established in Wellington in 1997. Characteristics of the first 100 injecting
      drug users with hepatitis C assessed through the clinic are presented. RESULTS:
      Of 51 patients found to be hepatitis C positive, five have received hepatitis C
      treatment, four at the outreach and one at a base hospital. 25 have been
      vaccinated for hepatitis B. The clinic has established trust and rapport with the
      injecting-drug-user community. CONCLUSIONS: The hepatitis outreach clinic is an
      innovative project, crossing the primary/secondary interface of health services
      provision and providing personal health services within a public health
      initiative. The success of this model indicates potential value in offering
      outreach hepatitis clinics for injecting drug users in the major cities to close
      a gap in health service provision.

PMID- 11346155
TI  - SmokeChange for changing smoking in pregnancy.
AB  - AIM: To measure the extent to which SmokeChange, a personalised intervene,
      enabled pregnant women to rede their exposure to tobacco smoke. METHODS: A cross
      section of general medical practices was randomly selected. General Practitioners
      (GPs) were to register all pregnant women with the SmokeChange programme. Smoking
      women were contacted by a SmokeChange Educator, who visited them at home. The
      Educator worked with women and their families for up to twelve months in order to
      support cognitive, environmental and behavioural changes to smoking. RESULTS: GPs
      registered 1,390 pregnant women. Current smoking, was reported by 437 (31.4%) and
      209 (47.8% of smokers) chose to enrol with the SmokeChange intervention
      programme. of these, 149 women (34.1% of smokers) continued with the programme
      for at least four visits. From this 'long' participation group, 28 (18.8%) had
      stopped smoking entirely by their last visit in pregnancy. Another 26 (17.4%)
      reported at least one cessation attempt, together with a reduction of smoking
      consumption by 63% at the end of pregnancy. The 95 (63.8%) continued smokers had
      reduced their smoking consumption by 40%. Substantial smokefree environment
      (homes and cars) changes were also made. CONCLUSIONS: The SmokeChange approach of
      personalised intervention, matched to individual readiness for change, was both
      acceptable to pregnant women and enabled participants to substantially reduce
      tobacco toxin exposure to themselves and their developing infants.

PMID- 11346156
TI  - Rural hospital amniotomy induction for women at or past term with a healthy
      pregnancy and a favourable cervix: is it a safe option?
AB  - AIM: To assess the safety and efficacy of amniotomy induction of labour for women
      at or past term with a healthy pregnancy and a favourable cervix. METHODS:
      Retrospective chart review of nine cases involving amniotrophy induction managed
      by the author since 1991, combined with a literature search for randomised
      controlled clinical trials of the use of amniotomy inducton. RESULTS: All nine
      women delivered within fourteen hours of amniotomy. The only serious complication
      was group B streptcoccal septicaemia in one newborn that developed four hours
      after birth. No randomised controlled clinical trials was found that examined the
      use of amniotomy alone in a rural setting to induce women at or past term with a
      healthy pregnancy and a favourable cervix. However, studies from secondary care
      institutions of women at or past term with a favourable cervix, being induced for
      a variety of reasons, demonstrate that amniotomy is both safe and effective.
      CONCLUSION: In appropriately selected women, the use of amniotomy induction in a
      rural maternity unit is both safe and effective.

PMID- 11346157
TI  - The burden of symptoms of asthma, allergic rhinoconjunctivitis and atopic eczema
      in children and adolescents in six New Zealand centres: ISAAC Phase One.
AB  - AIM: To describe the burden of symptoms of asthma, allergic rhinoconjunctivitis
      and atopic eczema in children in six New Zealand centres. METHODS: The
      International Study of Asthma and Allergies in Childhood (ISAAC) Phase One was
      undertaken in Auckland, Bay of Plenty, Hawke's Bay, Wellington, Nelson and
      Christchurch during 1992-1993. In each centre, approximately 3,000 six to seven
      year old children and 3,000 thirteen to fourteen year old adolescents were
      studied, a total of 37,592 participants. Both age groups answered written
      questionnaires and the adolescents a video questionnaire about asthma symptoms.
      RESULTS: The prevalences of symptoms were high, for asthma 25% and 30%, allergic
      rhinoconjunctivitis 10% and 19%, and atopic eczema 15% and 13% in each age group
      respectively. More than 40% of participants had symptoms in the last year of at
      least one condition, most commonly asthma. There were no significant differences
      among regions, except for six to seven year olds in Nelson who had significantly
      lower prevalences of some symptoms of asthma and allergic rhinoconjunctivitis.
      CONCLUSIONS: Asthma and allergies are common in New Zealand, with resultant
      morbidity and cost. However, there is little regional variation with the
      exception of lower rates in Nelson children. Explanations for these findings will
      be the subject of further studies.

PMID- 11346158
TI  - The Decade of Bone and Joint, 2000-2010.

PMID- 11346159
TI  - Methodology of the 1997 New Zealand National Nutrition Survey.
AB  - AIMS: To describe the development and use of the methodologies in the 1997 New
      Zealand National Nutrition Survey (NNS97). METHODS: NNS97 was a voluntary cross
      sectional population survey conducted over a twelve month period on 4,636 non
      institutionalized urban and rural New Zealand residents aged fifteen years and
      older. Survey data were collected in the participants' home and included: a self
      administered qualitative food frequency questionnaire, including questions on
      food preparation habits; a three-pass 24-hour diet recall; interviewer
      administered questions on diet supplement use, barriers to dietary change and
      participant perception of household food security; physical measurements
      including weight, height, three circumferences, two skinfolds and elbow breadth;
      blood pressure; and a blood sample to determine cholesterol and iron status.
      RESULTS: New methodologies developed for NNS97 included a computer based
      interview system, probability analyses for estimating prevalence of inadequate
      intake of selected nutrients, determination of iron status by both dietary and
      biochemical assessment, assessments of dietary supplement use and food security.
      A full range of quality control procedures at each stage of the data collection
      were also initiated. CONCLUSION: NNS97 has improved on previous New Zealand
      national nutrition survey methodologies, particularly with direct data capture
      and rigorous quality control procedures used in the collection of survey data.

PMID- 11346160
TI  - Obesity and body fat distribution in the New Zealand population.
AB  - AIMS: To report the prevalence of obesity and body fat distribution in the New
      Zealand population and to determine if there is a trend to increasing obesity and
      changes in body fat distribution. METHODS: Body weight, height, two skinfolds
      (triceps and subscapular), and waist and hip circumferences were measured on
      4,420 New Zealanders as part of the 1997 National Nutrition Survey (NNS97). These
      results are compared with data from the 1977 National Heart Foundation Survey
      (n=1,800) and the 1989 Life in New Zealand Survey (LINZ89) (n=3,300). RESULTS:
      35% of the population (40.4% males, 30.1% females) were classified as overweight
      and a further 17% as obese (14.7% males, 19.2% females) in NNS97 compared to 32%
      overweight and 11% obese in LINZ89. Body weight and body mass index have
      increased in the last two decades. In addition, there has been an increasing
      trend towards central obesity as estimated by waist to hip ratio and subscapular
      to triceps ratio. CONCLUSIONS: The increase in body weight, obesity, central
      obesity, and the proportion of the population likely to exhibit health risk
      indicators presents an increasing health problem in New Zealand.

PMID- 11346161
TI  - Declining levels of total serum cholesterol in adult New Zealanders.
AB  - AIM: To measure the average serum concentration of total cholesterol and high
      density lipoprotein cholesterol in a representative sample of New Zealanders.
      METHODS: Serum total and high density lipoprotein cholesterol levels were
      measured in a representative sample of 1,412 men and 1,741 :women aged 15 years
      or older who participated in the National Nutrition Survey (1997) of New
      Zealanders. RESULTS: The average serum total cholesterol concentration in men was
      the same as in women (5.7 mmol/L); however, younger women (44 years and under)
      tended to have lower levels and older women (55 years and over) higher levels of
      total cholesterol than men. Women in all age groups had higher average levels of
      high density lipoprotein cholesterol (1.4 mmol/L) than men (1.2 mmol/L). Ethnic
      differences were apparent with Maori men having significantly higher average
      levels of total cholesterol than their New Zealand European counterparts.
      CONCLUSIONS: Mean serum total cholesterol concentration in women has declined by
      0.3 mmol/L from 6.0 mmol/L (p<0.05) since the previous representative survey of
      New Zealanders (Life in New Zealand Survey, 1989), but by only 0.1 mmol/L in men,
      despite a similar reduction amongst men and women in the proportion of dietary
      energy derived from total and saturated fat. It is possible that weight gain in
      men and women during the last nine years is having a differential effect on serum
      cholesterol concentrations.

PMID- 11346162
TI  - Dietary iron intakes and biochemical iron status of 15-49 year old women in New
      Zealand: is there a cause for concern?
AB  - AIM: To assess dietary iron intakes and biochemical iron status of a nationally
      representative sample of nonpregnant 15-49 year old women (n=1,751) in New
      Zealand. METHODS: A cross-sectional national survey was conducted in 1996/97.
      Women were selected via a multistage stratified cluster sampling procedure with
      increased sampling of Maori and Pacific women. Dietary iron intakes were
      estimated using a 24-hour diet recall. Biochemical iron status was assessed on a
      non-fasting venipuncture blood sample (n=1,047) via haemoglobin, mean cell
      volume, erythrocyte zinc protoporphyrin, transferrin receptors and serum
      ferritin. RESULTS: Average daily dietary iron intakes ranged from 9.6 mg/day
      among Pacific women to 10.5 mg/day among Maori women; 41% of 20-49 year olds and
      45% of adolescents were at risk of low dietary iron intakes. The estimated
      percentage of 15-49 year old women with iron deficiency anaemia ranged from 1.4
      5.5%, and for iron deficiency without anaemia from 0.7-12.6% depending on the age
      group and criteria used. CONCLUSIONS: The overall estimated prevalence of
      suboptimal biochemical iron status among 15-49 year old women in New Zealand
      ranged from 7-13%, which compared favourably with premenopausal women living in
      other western countries. This situation is, however, a public health concern
      given the potential negative functional consequences associated with even mild
      iron deficiency.

PMID- 11346163
TI  - Attaining optimal bone status: lessons from the 1997 National Nutrition Survey.
AB  - AIMS: To examine the adequacy of calcium intake in relation to current
      recommendations, demographic differences in calcium intake and dietary sources in
      the New Zealand population. METHODS: 24-hour diet recall and qualitative food
      frequency data from the 1997 New Zealand National Nutrition Survey (NNS97) were
      used. RESULTS: No age-gender subgroups had median intakes meeting the latest
      (1998) US recommendations. Women's median intakes failed to meet even the
      considerably lower 1990 Australian recommendations. 20% of New Zealanders and one
      in four women had intakes below the UK Estimated Average Requirements for
      calcium. Intakes below the UK Lower Reference Nutrient Intake (the level at which
      the risk of deficiency is virtually 100%) were common (15-20%) among women aged
      15-18 years, those living in the most deprived areas or Maori. Milk and milk
      products were the major sources of the nation's calcium intake. CONCLUSION:
      Although other factors such as genetics, hormonal status, vitamin D status and
      exercise influence skeletal health, adequate calcium intakes are important in
      minimizing bone loss. A reduction in the proportion of New Zealanders with
      inadequate calcium intakes will most readily be achieved if more people meet the
      milk products Dietary Guideline (minimum of two servings daily). Health
      professionals can play an important role in raising perceptions of the benefits
      of adequate calcium intakes, promoting the milk products Dietary Guideline, and
      emphasising that lower fat diets can include adequate calcium through use of
      reduced fat milk products.

PMID- 11346164
TI  - Food security: is New Zealand a land of plenty?
AB  - AIM: To explore the concept of food security (when there is enough, appropriate
      and acceptable food available) in the adult New Zealand population using the
      National Nutrition Survey (NNS97). METHODS: The stepwise development of
      indicators of food security included a literature search and focus groups with
      low income women and men. Key issues surrounding the procurement and provision of
      food were determined and eight indicator statements prepared for inclusion in
      NNS97, to be addressed by each participant on behalf of their household. RESULTS:
      Prevalence was significantly higher (p<0.05) for females compared to males for
      the majority of indicator statements among New Zealand European & Others and
      Maori. New Zealand European & Others reported the most food security; Pacific
      people reported the least and Maori fell between the two. There was a significant
      increasing linear trend of food security with age (p<0.001), after adjusting for
      gender. "Food runs out in my/our household due to lack of money" was cited more
      often by female compared to male New Zealand European & Others in NZDep96
      quartiles III and IV. CONCLUSION: The issue of 'not having enough food' may be
      more prevalent in New Zealand than US or Australia. Among New Zealand European &
      Others the higher prevalence of insufficient food due to lack of money among
      females from NZDep96 quartiles III and IV suggests that males may be protected
      from this by their female partners. Food security needs to be improved among
      young adults, women, Maori and Pacific people in order to prevent longer term
      nutritional health consequences.

PMID- 11346165
TI  - Comparing the laparoscopic Burch colposuspension and the suburethral sling.

PMID- 11346166
TI  - World Wide Web medical consultations a global problem.

PMID- 11346167
TI  - The cost burden of asthma in New Zealand.

PMID- 11346168
TI  - The influence of rearing conditions on the physical growth of captive Japanese
      macaques (Macaca fuscata).
AB  - To clarify the influence of rearing conditions on the growth of various body
      parts of Japanese macaques (Macaca fuscata), two groups reared under different
      conditions, i.e., a group born and reared in open enclosures (Enclosure group)
      and another consisting of macaques born and reared in cages (Caged group), were
      somatometrically analyzed. Somatometric data on 36 measures of various body parts
      were collected from 77 males and 92 females. Growth in many body parts was
      smaller in the Caged group than in the Enclosure group. Body parts that exhibited
      large incremental increases were more sensitive to differences in rearing space
      at the infantile growth stage in both sexes. Recovery from delayed growth at the
      pubertal growth stage was found in many body parts. However, the size of some
      locomotor elements such as the wrist and hand, and ankle and foot strongly
      reflected limitations of space and changes due to this were irreversible. Females
      were more sensitive than males to such differences in rearing conditions. We
      conclude that open enclosures with ample rearing space are necessary for the
      innate growth of Japanese macaques to occur.

PMID- 11346169
TI  - Release of dopamine and ATP from PC12 cells treated with dexamethasone, reserpine
      and bafilomycin A1.
AB  - The amounts and time courses of dopamine and ATP released from perfused PC12
      cells were examined using a simultaneous on-line recording system. High KCl (60
      mM) caused dopamine and ATP release with similar time courses. The relative
      amount of dopamine to ATP in the effluent was 9.5. In PC12 cells cultured with
      dexamethasone, reserpine or bafilomycin A1 for 2 days, these drugs did not affect
      increases of intracellular Ca2+ in response to high KCl. Dexamethasone doubled
      the amount of dopamine release induced by high KCl without changing the amount of
      ATP release. High KCl failed to cause dopamine release in reserpine-treated cells
      but evoked ATP release. Bafilomycin A1 decreased both high KCl-induced dopamine
      and ATP release. The ratio of released ATP to total adenine nucleotides and
      adenosine in response to high KCl was not changed by treatment with the drugs.
      These results suggest that dopamine and ATP are simultaneously released from
      secretory vesicles of PC12 cells, in which they are stored via different
      pathways. Similar to dopamine uptake into secretory vesicles, the H+-gradient
      across the vesicular membrane developed by vacuolar ATPase may play an important
      role in the vesicular uptake of ATP.

PMID- 11346170
TI  - 2-Bromopropane induced germ cell apoptosis during spermatogenesis in male rat.
AB  - 2-Bromopropane (2-BP) causes testicular toxicity in humans and rats. However, the
      germ cell degeneration of testicular toxicity by 2-BP has not been understood. 2
      BP at doses of 135, 405, and 1,355 mg/kg/day was daily injected subcutaneously
      into Sprague-Dawley rats for 28 days. At the dose of 1,355 mg/kg/day, 2-BP
      significantly decreased the weights of body and testes, eipididymis, seminal
      vesicle, and prostate, as well as daily sperm production. Atrophy of seminiferous
      tubules accompanied with degeneration of germ cells such as spermatogonia,
      spermatocytes, and elongated spermatids was observed in the testes of rats
      exposed to the 405 mg/kg/day and 1,355 mg/kg/day of 2-BP. TUNEL-positive germ
      cells were appeared in the 405 and 1,355 mg/kg/day of 2-BP-treated groups. In
      addition, ultrastructure alterations of apoptotic germ cells were observed by the
      electron microscopy study. Dead elongated spermatids were observed at 1,355
      mg/kg/day after 28 days exposure. These results suggest that 2-BP impair
      spermatogenesis may result from apoptotic germ cell death.

PMID- 11346171
TI  - Effect of dopamine on excretory urographic image quality and the prevention of
      contrast-induced nephropathy in dogs.
AB  - The effect of low dose dopamine on the excretory urographic image quality and
      contrast media-induced nephropathy in normal dogs (experiment 1) and the dogs
      with decreased renal function (experiment 2) were assessed. In experiment 2,
      decreased renal function was induced by gentamicin overdose. In each experiment,
      animals were divided into 3 groups. In group 1, only contrast medium (iohexol)
      was administered. In group 2, contrast medium plus intravenous fluid (0.9%
      saline) were administered. And in group 3, contrast medium plus intravenous fluid
      and low dose dopamine were administered. Investigated parameters included
      intrarenal resistive index (RI), serum BUN and creatinine concentrations,
      contrast medium elimination time and radiographic image quality. In experiment 1,
      RI of group I increased at 80 min after contrast medium administration (p<0.05),
      but RI of group 3 decreased at 48 and 72 hr (p<0.05). Serum BUN concentration of
      group 1 was higher than that of group 2 and 3 (p<0.05); in radiographic
      examination, contrast medium elimination time decreased in group 2 and 3, but
      image quality of group 2 was inferior to that of group 3. In experiment 2, image
      quality of group 3 only provided adequate visualization of renal structures. The
      formula of contrast medium plus low dose dopamine was found to provide good
      nephrogram and pyelogram image quality without supplemental contrast medium, and
      to protect renal tubules from prolonged exposure to concentrated contrast medium.

PMID- 11346172
TI  - Mechanism of carbon monoxide-induced relaxation in the guinea pig ileal smooth
      muscle.
AB  - The mechanism of carbon monoxide (CO)-induced relaxation were investigated in the
      guinea-pig ileum. CO (10%) inhibited the 40 mM KCl-induced contraction. This
      effect was antagonized by ODQ (1 microM), a soluble guanylate cyclase inhibitor.
      In contrast, CO did not inhibit the 40 mM KCl-induced increase in cytosolic Ca2+
      level ([Ca2+]i). Cumulative addition of KCl induced a graded increase in both
      [Ca2+]i and muscle tension. In the presence of CO, the increase in muscle tension
      was attenuated whereas the increase in [Ca2+]i was only slightly decreased. Thus,
      the [Ca2+]i-tension relationship constructed by cumulative addition of KCl
      shifted downwards in the presence of CO. Using the patch clamp, CO was found to
      have little effect on the peak Ba currents (I(Ba)) when voltage was stepped from 
      60 mV to 0 mV. From these results, we conclude that CO inhibits contraction of
      guinea-pig ileum mainly by the decrease in the sensitivity of contractile
      elements to Ca2+ via a cyclic GMP-dependent pathway but not by the inhibition of
      L-type Ca2+ channel.

PMID- 11346173
TI  - Lysophosphatidylcholine decreases delayed rectifier K+ current in rabbit coronary
      smooth muscle cells.
AB  - Lysophosphatidylcholine (LPC), which exists abundantly in lipid fraction of
      oxidized low density lipoprotein, has been implicated in enhanced agonist-induced
      contraction and increase of intracellular Ca2+. The effect of LPC on the activity
      of delayed rectifier K+ current (I(dK)), which is a major determinant of membrane
      potential and vascular tone under resting condition, was examined in rabbit
      coronary smooth muscle cells using whole cell patch clamping technique.
      Application of LPC to the bath solution caused a concentration-dependent
      inhibition of I(dK), and the concentration to produce half-maximal inhibition was
      1.51 microM. This effect of LPC on I(dK) was readily reversed after washout of
      LPC in the bath. The steady-state voltage dependence of I(dK) was shifted to
      positive direction by both extra- and intracellular application of LPC.
      Staurosporine (100 nM) pretreatment significantly suppressed the LPC-induced
      inhibition of I(dK). These results suggest that LPC inhibits I(dK) in rabbit
      coronary smooth muscle cells by a pathway that involves protein kinase C, and the
      LPC-induced inhibition of I(dK) may be, at least in part, responsible for the
      abnormal vascular reactivity in atherosclerotic coronary artery.

PMID- 11346174
TI  - Transfer of canine embryos at various developmental stages recovered by
      hysterectomy or surgical uterine flushing.
AB  - In dogs, embryo transfer (ET) techniques such as induciton of excessive ovulation
      and synchronization of estrus have not progressed well. Therefore, using embryos
      at various developmental stages, ET was investigated in dogs from a beagle colony
      in which the ovulation days were close, as estimated by the progesterone level.
      Embryos were, recovered 8-11 days after ovulation (4-9 days after mating) by
      excising the oviducts and uteri (excision method) in 16 animals and by surgical
      flushing of the uteri at laparotomy (surgical method) in 3 animals. In 24 dogs
      with -4 to +2 days of difference in the timing of ovulation between donor and
      recipient dogs, 1-10 embryos at the 8-cell to blastocyst stages were transferred
      per animal. The mean embryo recovery rate by the excision method (97.1%) was
      significantly higher than that by the surgical method (42.5%) (p<0.01). Twelve
      (57.1%) of 21 animals with -1 to +2 days difference in ovulation day became
      pregnant after the transfer of 8-cell to blastocyst stage embryos. Although 3
      dogs with -4 to -2 days of difference of ovulation day underwent ET of morula or
      compacted morula, none of these dogs became pregnant. The mean ratio of the
      number of newborns to the number of transferred embryos was only 51.9%. The mean
      duration of the period between ovulation and delivery in the pregnant recipients
      was 65.8 days, which tended to be longer than that in natural mating. These
      results demonstrate that pregnancy can be induced by ET at the 8-cell to
      blastocyst stage in dogs with -1 to +2 days difference in ovulation day.

PMID- 11346175
TI  - High plasma estradiol-17beta levels in dogs with benign prostatic hyperplasia and
      azoospermia.
AB  - The semen quality of 22 dogs (4 to 7 years old) with benign prostatic hyperplasia
      (BPH) was examined at the hospital of our university, and 4 of the 22 BPH dogs
      were diagnosed as azoospermic. The mean peripheral plasma estradiol-17beta (E2)
      level (17.3 pg/ml) of the 18 BPH dogs with spermatogenic function was higher than
      that of 5 normal male dogs and their mean T level (1.7 ng/ml) was lower. The mean
      E2 level (27.3 pg/ml) of the 4 BPH dogs with azoospermia was significantly higher
      than the value in the BPH dogs with spermatogenic function (P<0.01), and the mean
      T level (1.1 ng/ml) was significantly lower (P<0.05). Five normal male dogs were
      given 10 intramuscular injections of estradiol benzoate (E2B) 5 microg/kg, at 3
      day intervals to investigate the relationship between high plasma E2 levels and
      the cause of the BPH and azoospermia. Their testes and prostates were measured
      and biopsied both before and 30 days after the start of E2B injections. At 30
      days after the start of the E2B injections, the mean peripheral plasma T levels
      had decreased by half, and the mean testicular volume had decreased to 88% of
      original volume. The numbers of spermatocytes, spermatids, and spermatozoa in the
      seminiferous tubules of all of the dogs were significantly lower (P<0.05, 0.01).
      In addition, the mean prostatic volume increased to 130%, the mean height of the
      glandular epithelium decreased, and the glandular lumen became increased in
      diameter. These findings indicate that both BPH and serious spermatogenic
      dysfunction may be simultaneously induced by protracted high plasma E2 levels in
      dogs.

PMID- 11346176
TI  - Atopic NC/Nga mice as a model for allergic asthma: severe allergic responses by
      single intranasal challenge with protein antigen.
AB  - Since certain characters of allergic asthma are common with other allergic
      disorders like atopic dermatitis, the possible relationship in etiology is
      expected. Herein, we investigated whether NC/Nga mice, an inherent animal model
      for human atopic dermatitis, are inclined to allergic asthma. A single intranasal
      challenge of NC/Nga mice immunized with ovalbumin (OVA) resulted in an increase
      in plasma levels of OVA-specific IgE, and typical pathological aspects of
      allergic asthma characterized by infiltration of numerous eosinophils, mucus
      hyper production of bronchial epithelial cells. Moreover, airway
      hyperresponsiveness to inhaled acetylcholine and marked enhancement of airway
      resistance after the challenge were observed as compared to control BALB/c mice.
      Delayed expression of mRNA of eosinophil active chemokines, interleukin-5,
      eotaxin, macrophage inflammatory protein-1alpha in concert with eosinophilia was
      determined in the lung of NC/Nga mice. These results suggest that asthmatic
      responses developed in NC/Nga mice challenged with OVA are very similar to human
      allergic asthma, and that NC/Nga mice are a useful model to elucidate various
      aspects of allergic asthma.

PMID- 11346177
TI  - Infectivity and pathological changes in murine clonorchiasis: comparison in
      immunocompetent and immunodeficient mice.
AB  - The main complications of clonorchiasis are periportal inflammation, biliary
      hyperplasia, periductal fibrosis, and subsequently the development of biliary
      tumors in the liver. This study was undertaken to compare the infectivity and
      histopathologic changes between in immunocompetent FVB/NJ and BALB/cA strains,
      and immunodeficient severe combined immunodeficient (SCID) and athymic nude mice
      after the metacercariae of Clonorchis (C.) sinensis were infected. The experiment
      showed that C. sinensis was very infective in all strains studies, but the status
      of worm development, infectivity, recovery rate, and morphological changes of
      livers were very different in each strain. FVB/NJ mice showed more worm recovery
      than any other strain. Histopathologically the liver of FVB/NJ mice at 4 weeks
      postinfection showed marked cystic and fibrotic changes, in which C. sinensis was
      fully developed with ovum production, severe infiltration of inflammatory cells,
      mostly eosinophils, and high degrees of biliary hyperplasia. In SCID and nude
      mice, there were few foci of inflammatory cells even at 8 weeks postinfection in
      periportal areas of the liver, associated with no development into adult worm
      with ovum production. Fibrosis occurring at 4 weeks postinfection was highly
      correlated with inflammatory infiltration when each strain was compared. We
      suggest that massive infiltration of eosinophil and plasma cells caused by the
      infection might initiate cystic formation and fibrosis. These data demonstrate
      that the infection of C. sinensis might be related to pathologic consequences of
      inflammatory cell infiltration, cystic formation and fibrosis which might play a
      role in the defense mechanism against the parasitism in the liver of each strain.
      The FVB/NJ mouse model might be very helpful in elucidating the mechanism for
      human clonorchiasis.

PMID- 11346178
TI  - Heparin inhibits plaque formation by cell-free Marek's disease viruses in vitro.
AB  - The mechanisms of Marek's disease virus (MDV) entry to host cells have not yet
      been analyzed. Heparan sulfate (HS) on the cell surface serves as a receptor for
      several herpesviruses in mammalian species. In this study, we demonstrated that
      plaque formation by cell-free MDV is inhibited by the addition of soluble heparin
      to the cell culture. Moreover, pretreatment of susceptible cells, chicken embryo
      fibroblasts, with heparinase, partially reduced infectivity of the cell-free MDV.
      From these results, it was suggested that the MDV entry, at least in the case of
      cell-free MDV, is dependent on the presence of cell surface glycosaminoglycans,
      principally HS.

PMID- 11346179
TI  - Modified protection against Toxoplasma gondii lethal infection and brain cyst
      formation by vaccination with SAG2 and SRS1.
AB  - Numerous studies have supported the importance of immunity to SAG1, the most
      predominant antigen of Toxoplasma tachyzoite, in protection against Toxoplasma
      gondii infection. Nevertheless, vaccination with SAGI provides insufficient
      protection when compared with that of Toxoplasma lysate (TL). In order to screen
      the Toxoplasma antigens for immunogenic potential shown by modified protection or
      induction of specific immune response after infection, recombinant antigens were
      prepared in Eschericha coli using DNA fragments corresponding to SAG1, SAG2,
      SAG3, SRS1 and P54 of T. gondii RH strain maintained in our laboratory. Each of
      the recombinant antigen products or a mixture of the five antigens (Mix) was used
      to vaccinate mice. Mice then received a lethal dose of T. gondii. Up to 25% of
      the mice vaccinated with SAG2, SRS1, P54 and Mix survived, whereas there were no
      survivors in gene 10- (negative control), SAG1- and SAG3- vaccinated groups. In
      all the survivors, brain cysts were not observed. Conversely, vaccination with TL
      almost completely protected mice in the acute phase but permitted brain cyst
      formation and resulted in gradual decrease of survivors to 33% during 4 months of
      experiments. Western blot analysis on convalescent sera showed an extensive IgG
      induction to a 30 kDa antigen in TL-vaccinated mice, a 22 kDa in SAG2-vaccinated
      mice and a 55 kDa in P54-vaccinated mice. The protection modified by boost in
      specific antibody is suggestive of the immunogenic potential of SAG2, SRS1 and
      possibly P54 against T. gondii infection.

PMID- 11346180
TI  - Respiratory and cardiovascular reflexes elicited by nasal instillation of
      capsaicin to anesthetized, spontaneously breathing dogs.
AB  - Cardiopulmonary reflexes elicited by capsaicin (CAPS) instilled into the nasal
      passages were determined in 6 anesthetized dogs breathing spontaneously. Nasal
      instillation of CAPS (10 microg/ml, 10 ml) induced: 1) apneic response
      characterized by an increase in expiration time; 2) bronchoconstrictor response
      characterized by an increase in lung resistance and a decrease in dynamic
      compliance; and 3) cardiovascular response characterized by a decrease in heart
      rate and an increase in arterial blood pressure. These reflex responses to CAPS
      were attenuated by pretreatment with a higher dose of CAPS (100 microg/ml, 10
      ml), suggesting desensitization of CAPS-sensitive endings. These results suggest
      that marked cardiopulmonary reflexes are produced by nasal CAPS instillation,
      which may result, at least in part, from stimulation of nasal CAPS-sensitive
      sensory afferents.

PMID- 11346181
TI  - Comparison of the growth inhibitory effects of canine IFN-alpha, -beta and -gamma
      on canine cells infected with Neospora caninum tachyzoites.
AB  - The growth inhibitory effects of recombinant canine interferon alpha (IFN-alpha),
      beta (IFN-beta) and gamma (IFN-gamma) were examined on Madin-Darby canine kidney
      cells infected with Neospora caninum tachyzoites. The parasite growth was
      inhibited by all IFNs in a dose-dependent manner. IFN-gamma inhibited the
      parasite growth with greater efficacy than IFN-alpha or IFN-beta. Moreover, the
      effect of IFNs on N. caninum growth associated with the suppression of the host
      cell viability. The present study indicates IFN-alpha and -beta, besides IFN
      gamma, play a crucial role for N. caninum growth in host cells.

PMID- 11346182
TI  - Nine cases of granular cell tumors in B6C3F1 mice.
AB  - The histological characteristics of 9 cases of granular cell tumors (GCTs)
      observed in B6C3F1 mice were examined to determine their cellular origin. Seven
      of the 9 cases were found in the uterus and other 2 cases were in the
      subcutaneous tissue. Tumor cells had abundant granules in the cytoplasm which
      were stained with PAS and were resistant to diastase treatment.
      Ultrastructurally, the granules were identified as lysosomes. The cell surface
      had cytoplasmic processus showing interdigitation with adjacent cells. A
      character feature of the tumor cells was the presence of a desmosome-like
      structure on their cell surface but no basal lamina was demonstrated. Although
      GCTs have been considered to be derived from Schwann cells on the basis of their
      ultrastructural features and S-100 protein-immunopositive findings, the absence
      of basal lamina in the present cases may raise a controversy as to their origin.

PMID- 11346183
TI  - Effect of osaterone acetate administration on prostatic regression rate,
      peripheral blood hormone levels and semen quality in dogs with benign prostatic
      hypertrophy.
AB  - The effects of osaterone acetate (OSA), which is an anti-androgen agent being
      developed as a therapeutic drug for benign prostatic hypertrophy (BPH) in dogs,
      on the degree of prostatic regression and semen qualities were investigated.
      Prostatic regression was compared between dogs with and without orchidectomy.
      Five male beagles aged 5-9 years were used in the experiment. OSA was orally
      administered at doses of 0.2 mg/kg and 0.5 mg/kg for one week. The prostatic
      regression rate one week after the end of administration was 62.6% on average. In
      the orchidectomized group, the mean regression rate one week after orchidectomy
      was 60.1%. However, the prostate became enlarged 6 months after administration,
      compared to the size prior to administration. The above findings suggested that
      OSA is clinically applicable as a therapeutic drug for BPH in dogs, and inhibits
      prostatic hypertrophy during the early phase.

PMID- 11346184
TI  - Mange caused by Sarcoptes scabiei (Acari: Sarcoptidae) in wild raccoon dogs,
      Nyctereutes procyonoides, in Kanagawa Prefecture, Japan.
AB  - Parasitological and histopathological examinations were performed in 25 raccoon
      dogs (Nyctereutes procyonoides) obtained in Kanagawa Prefecture, Japan, all of
      which were found to be heavily infected with Sarcoptes scabiei. The mites
      detected on these raccoon dogs were morphologically indistinguishable from the
      human species, and no Demodex mites were detected. Histopathological examinations
      showed prominent hyperkeratosis and acanthosis with eczema, and numerous burrows
      containing mites were observed in the epidermis. The enzootic dermatitis of wild
      raccoon dogs in recent years was clearly demonstrated to be caused by S. scabiei
      in the present study.

PMID- 11346185
TI  - Effects of estrous cycle on the mouse kidney morphology.
AB  - Although mice kidney morphology shows various sexual dimorphisms, the effect of
      the estrous cycle has not previously been discussed. In this study, we
      investigated the effects of the estrous cycle on kidney morphology, including
      renin-positive areas, of female DBA/2 mice. No effects were confirmed in most of
      the histometrical parameters, however, the percentage of the renal corpuscles in
      which cuboidal epithelium covered under 50% of the parietal layer was
      significantly higher during estrus compared to that during anestrus.

PMID- 11346186
TI  - Enhanced production of IL-1beta and IL-6 following endotoxin challenge in rats
      with dietary magnesium deficiency.
AB  - Serum IL-1beta, IL-6 and TNFalpha were not detected in control and Mg-deficient
      rats. These three cytokine levels in serum were increased after endotoxin
      challenge (1 mg/kg., i.p.), and the increase of IL-1beta and IL-6, but not
      TNFalpha, was significantly larger in Mg-deficient rats than in controls. Levels
      of mRNA for IL-1beta, IL-6 and TNFalpha in alveolar macrophages showed a tendency
      to decrease during Mg deficiency, but the levels of IL-1beta and TNFalpha mRNAs
      after endotoxin challenge were higher in Mg-deficient rats than in controls.
      These results suggest that the increased synthesis of cytokines by alveolar
      macrophages might contribute, in part, to high sensitivity to endotoxin during Mg
      deficiency.

PMID- 11346187
TI  - Atopic NC/Nga mice as a model for allergic asthma: cytokine profiles and
      eosinophil productivity of bone marrow.
AB  - In previous study, NC/Nga mice with experimentally induced asthma showed severe
      eosinophilia. To explore the mechanism, profiles of representative cytokines
      interleukin (IL)-4, IL-5, and interferon (IFN)-gamma were examined in
      bronchoalveolar lavage fluid. The level of only IFN-gamma was lower in NC/Nga
      mice than control BALB/c mice. Furthermore, bone marrow cell culture system under
      the presence of eosinopoietic cytokines, which induce the differentiation of
      progenitor cells into mature eosinophils, showed that a larger number of
      eosinophils differentiated from NC/Nga mice derived bone marrow cells than from
      control BALB/c mice. These results may imply the possibility that severe
      eosinophilia in the NC/Nga mice are attributable to lower production of IFN-gamma
      and higher eosinophil productivity of bone marrow cells.

PMID- 11346188
TI  - A case of a bitch with imperforate hymen and hydrocolpos.
AB  - A 38-month-old female Golden retriever was presented with dysuria and dyschezia.
      It was difficult to visualize the vagina by vaginoscopy due to a cystic polyp on
      the hymen. The polyp was 2 x 3 cm in diameter, round, and pink in color. From
      clinical and imaging evaluations the original diagnosis was mucometra or
      pyometra. From endoscopic examination of the vagina an imperforate hymen was
      finally diagnosed. The ovaries, uterus, and half of the vagina were removed
      through a median abdominal incision. The vagina contained about 1.5 liters of
      fluid, but the uterus and ovaries appeared normal. This is a rare case with
      imperforate hymen and hydrocolpos with a polyp on the hymenal membrane in bitch.

PMID- 11346189
TI  - Microsatellite polymorphism in intron 14 of the canine BRCA1 gene.
AB  - Microsatellite polymorphism due to differences in CT dinucleotide repeats was
      demonstrated in intron 14 of the canine BRCA1 gene. Genotype analysis of 103
      unrelated dogs from 30 different breeds detected the presence of five alleles,
      including 10 of the expected 15 genotypes. Gene frequencies were biased and all
      alleles with the exception of one were below 0.1. This polymorphism, which occurs
      at the intron of canine BRCA1 should prove to be a useful marker for detecting
      the loss of heterozygosity (LOH). One of the more notable findings of the present
      study was the detection of homozygotes of rare alleles. This finding identified
      an accumulation of rare alleles in specific canine breeds and demonstrated the
      usefulness of this characteristic for the biological study of dog evolution.

PMID- 11346190
TI  - Combined hepatocellular and cholangiocellular carcinoma in a dog.
AB  - A transitional type of combined hepatocellular and cholangiocellular carcinoma
      developed in a 12-year-old male Yorkshire terrier dog. The tumor was
      histologically composed of both hepatocellular carcinoma and cholangiocellular
      carcinoma components, and both elements were closely intermingled. Intraluminal
      mucin accumulation in cytokeratin-positive tubular/glandular structures was
      observed within the cholangiocellular carcinoma components and this feature was
      useful histological marker for a differential diagnosis between combined
      hepatocellular and cholangiocellular carcinoma and a pseudoglandular type of
      hepatocellular carcinoma. This primary hepatic tumor is extremely rare in dogs.

PMID- 11346191
TI  - Antipsychotic-associated weight gain and clinical outcome parameters.
AB  - Weight gain has been observed with many of the antipsychotics, including the
      atypical antipsychotics. The assessment of whether, and to what degree, a drug
      causes changes in body weight is not straightforward, since clinical studies
      performed during a drug development program are not designed to measure changes
      in body weight. Even when weight change data are obtained from adverse event data
      or from part of the vital signs measured during a study, assessment is not
      standardized. Nevertheless, evidence points to the fact that weight gain with the
      atypical antipsychotics is becoming an increasing problem. This review examines
      whether antipsychotic-associated weight gain, when it occurs, is associated with
      clinical outcome parameters.

PMID- 11346192
TI  - Antipsychotic-induced weight gain: a review of the literature.
AB  - With the availability of the so-called novel antipsychotic agents, extrapyramidal
      symptoms are becoming decreasingly problematic for patients with schizophrenia,
      and simultaneously, a new symptom is emerging as a preeminent concern. This side
      effect is weight gain and its metabolic concomitants. This article reviews what
      is currently known about antipsychotic-induced weight gain, describes the
      magnitude of the problem, briefly touches on mechanisms of action, and addresses
      the correlation of interindividual variations in magnitude of weight gain. In
      addition, we address questions about the effects of weight gain on compliance and
      whether or not there is a correlation between weight gain and therapeutic
      efficacy. Finally, we address medical consequences of weight gain and review the
      literature supporting various treatment options for antipsychotic-induced weight
      gain. As will be seen, this is an area of research in its infancy, and much work
      remains to be done.

PMID- 11346194
TI  - The clinical implications of weight gain in schizophrenia.
AB  - The tendency of most of the second generation antipsychotics to induce weight
      gain to a larger extent than that of traditional neuroleptics has renewed the
      interest in weight problems of patients with schizophrenia. Drug-induced weight
      gain has been identified as a major risk factor for various medical disorders
      that might be responsible for the increased morbidity and mortality rates of
      patients suffering from schizophrenia. Also, it has a major impact on compliance.
      This article focuses on the clinical relevance of increased body weight in
      schizophrenia. It outlines screening and management options to prevent and/or
      manage weight gain associated with schizophrenia in everyday clinical practice.
      The first strategies should be to identify obesity-prone patients at the
      beginning of treatment and provide information (to patients and caregivers) about
      the risks of weight gain and its consequences. Additionally, the possibility of
      weight gain calls for a regular monitoring of weight and weight-related
      laboratory parameters. The patients should also be offered dietary advice as well
      as regular exercise and behavior modification programs. Physicians must be aware
      of the problem of weight gain associated with schizophrenia and choose
      antipsychotic medication carefully, especially in patients at high risk for
      weight gain.

PMID- 11346195
TI  - The pharmacology of weight gain with antipsychotics.
AB  - In general, antipsychotic agents have diverse actions on a wide range of
      neurotransmitter systems. Data strongly suggest that a number of these systems
      may play a role in the regulation of body weight. In addition to having very
      distinct pharmacologic profiles, individual agents possess discrete weight gain
      liabilities. This article briefly reviews the evidence for the involvement of
      specific neurotransmitter systems in the control of body weight and describes the
      relevant pharmacologic characteristics of individual antipsychotic agents. By
      comparing the pharmacologic profiles of specific antipsychotic agents with their
      respective weight gain liabilities, this article attempts to gain an insight into
      the specific receptors underlying a drug's propensity to induce weight gain.
      However, there is still much to be learned concerning weight control mechanisms,
      and the role of many of the receptors at which antipsychotic agents are active
      remains unclear. In spite of this, an overview of current knowledge in the field
      may facilitate prediction of a potential novel antipsychotic agent's weight gain
      liability.

PMID- 11346196
TI  - Early enteral nutrition in severe acute pancreatitis: a way of providing
      nutrients, gut barrier protection, immunomodulation, or all of them?

PMID- 11346197
TI  - Bile-induced adenosine triphosphate depletion and mucosal damage during reflux
      esophagitis.
AB  - BACKGROUND: This study was designed to investigate the role of bile in a large
      animal model of acute esophageal reflux disease. METHODS: An agar electrode was
      used to measure the transmucosal potential difference of the esophagus in
      anaesthetized dogs. The vascular permeability index and the epithelial
      permeability index of the mucosa were evaluated by means of the Evans blue and
      the sodium-fluorescein clearance method, respectively. The tissue adenosine
      triphosphate (ATP) level and the myeloperoxidase activity were determined from
      tissue biopsies, while the degree of mucosal damage was evaluated histologically
      on a grade 0-100 scale. Group 1 (n = 8) served as saline-treated control; groups
      2 (n = 8), 3 (n = 5) and 4 (n = 5) were exposed for 4 h to canine bile alone, to
      hydrochloric acid + bile, or to hydrochloric acid alone, respectively. RESULTS:
      In Groups 2, 3 and 4 the degree of mucosal damage was significantly increased,
      and a 4-fold elevation in myeloperoxidase activity was observed. The transmucosal
      potential difference was decreased significantly below the control level, while
      the vascular and epithelial permeability indices were significantly increased
      compared with the control values. Bile, but not hydrochloric acid, evoked a
      significant (40%) decrease in the ATP level of the esophageal tissue.
      CONCLUSIONS: We propose that mucosal dysfunction, structural damage and leukocyte
      invasion during hydrochloric acid-induced esophageal injury are exacerbated by
      bile-induced changes in tissue ATP concentrations during experimental esophageal
      reflux disease.

PMID- 11346198
TI  - Expression of a specific mucin type recognized by monoclonal antibodies in the
      rat gastric mucosa regenerating from acetic acid-induced ulcer.
AB  - BACKGROUND: Detailed research on the healing process of gastric mucosa from
      injury due to various necrotizing agents is important for regenerating medicine
      as well as for estimating the quality of ulcer healing. To elucidate this issue,
      we prepared monoclonal antibodies reacting with mucin molecules present in the
      specific region and layer of the gastrointestinal mucosa. METHODS: Acetic acid
      induced gastric ulcers were prepared in 8-week-old male Wistar rats. Following 24
      h fasting, the animals were killed at 20, 30 and 50 days after acid insult and
      their stomachs were removed immediately. Serial paraffin sections of the ulcer
      area were made and immunostained with three distinct monoclonal antibodies. RGM21
      and HIK1083 react with mucins derived from the surface mucous cells of the corpus
      and the gland mucous cells of corpus and antrum, respectively. HCM31 stains
      sialomucin present in the small intestine and colonic mucosa of rat, but does not
      react with the intact gastric mucosa, except in the very narrow cardiac gland
      area. RESULTS: On the 20th day after ulcer preparation, the cells stained with
      RGM21 and HIK1083 were restricted only to the surface layer and the bottom layer
      of regenerating epithelia, respectively. HCN31 staining covered most of the
      regenerating epithelia. On the 30th day, the staining of HCM31 was enhanced in
      the regenerating area. Staining of RGM21 did not change, but the HIK1083 stained
      area increased in the lower part of the regenerating epithelia. On the 50th day,
      the staining with HCM31 weakened markedly in the lower part, and this area was
      occupied with HIK1083 positive cells. CONCLUSION: A notable but temporary
      expression of a kind of sialomucin specifically stained with HCM31 was observed
      in the regenerating epithelia during the healing stage of acetic acid-induced
      gastric damage.

PMID- 11346199
TI  - Presence of gastric autoantibodies impairs gastric secretory function in patients
      with Helicobacter pylori-positive duodenal ulcer.
AB  - BACKGROUND: Although the association between Helicobacter pylori infection and
      gastric autoimmunity is now well established, to date little is known about the
      significance of anticanalicular autoantibodies in patients with duodenal ulcer
      (DU). We therefore investigated the prevalence of serum antiparietal cell
      autoreactivity in DU patients as well as the relationship between these
      autoantibodies, gastric histopathology and gastric secretory function in this
      setting. METHODS: Forty-one consecutive patients with H. pylori-positive DU were
      initially recruited. In all patients, basal (BAO) and pentagastrin stimulated
      acid output (PAO), fasting and meal-induced serum gastrin levels, as well as
      serum pepsinogen I concentrations, were measured. Antral and body gastritis was
      evaluated according to the Sydney system. Serum anticanalicular autoreactivity
      was determined by the indirect immunoperoxidase technique. RESULTS: Serum
      anticanalicular autoantibodies were found in 7 out of 34 patients (20%). The
      presence of these antibodies was associated with a significantly higher grade of
      body gastritis (activity: 1.9 versus 0.9) as well as with significantly higher
      fasting and meal stimulated gastrin levels (mean fasting gastrin, 76.4 (15.2)
      microg/ml versus 59.3 (20.5) microg/ml). In addition, PAO values were
      significantly lower in patients with gastric autoantibodies than in those without
      this autoreactivity (mean 0.35 (0.16) mmol kg(-1)h(-1) versus 0.49 (0.16)mmol kg(
      1)h(-1)). In contrast, no significant differences were found between patients
      with and without anticanalicular autoantibodies as regards fasting serum
      pepsinogen I concentrations. CONCLUSIONS: Serum anticanalicular autoantibodies
      can be detected in 20% of patients with DU and are associated with a more severe
      pattern of body gastritis, higher gastrin levels and decreased peak acid
      secretion values. Their presence could account for the normal or reduced acid
      output which can be seen in a subset of DU patients.

PMID- 11346200
TI  - Low incidence of Helicobacter pylori infection in patients with duodenal ulcer
      and chronic liver disease.
AB  - BACKGROUND: Duodenal ulcer (DU) is a common problem in patients with chronic
      liver disease (CLD) and with inadequate response to H2 receptor antagonists.
      Omeprazole might be more effective. In DU-CLD patients, Helicobacter pylori
      prevalence is low. Nitric oxide is increased in gastric mucosa in cirrhosis.
      Oxygen-free radicals have a role in gastric inflammation and are abnormal in CLD.
      Nitrotyrosine is a marker of nitric oxide and oxygen-free radical toxic mucosal
      reaction. METHODS: Sixty-nine patients were divided into 2 groups: control (26
      patients with DU) and CLD groups (43 patients, DU-CLD). Omeprazole was given (40
      mg/day) for 2 or 4 weeks. Symptoms and endoscopy findings were recorded before
      and after treatment. Antral biopsy specimens were stained for H. pylori and
      nitrotyrosine. RESULTS: Clinical features of DU are similar in patients with and
      without CLD. The main presentation was epigastric pain (70%) and bleeding (23%).
      Healing rate with omeprazole was higher in DU-CLD patients (90.7%) than in
      controls (80.8%). H. pylori was much lower in DU-CLD patients (51.2%) than
      controls (96.2%). Nitrotyrosine staining was negative in normal controls (0%) and
      positive in control-DU (100%), CLD-H. pylori positive (81%), and CLD-H. pylori
      negative (91%) cases. CONCLUSIONS: DU in patients with CLD is not different
      clinically from those without CLD. Omeprazole effectively and safely treats DU in
      CLD. Nitric oxide and free oxygen radicals may result in gastric mucosal changes
      in CLD similar to that caused by H. pylori.

PMID- 11346201
TI  - Contractile responses to natural tachykinins and selective tachykinin analogs in
      normal and inflamed ileal and colonic muscle.
AB  - BACKGROUND: Tachykinins and acetylcholine are main physiological motility
      stimulators in the gut by their effects exerted through neurokinin and muscarinic
      receptors. METHODS: Longitudinal and circular muscle strips from normal ileum and
      colon or corresponding tissues from patients with inflammatory bowel disease were
      studied in organ baths. Contractile responses to the tachykinins substance P,
      neurokinin A, neurokinin B and neuropeptide gamma and specific analogs for their
      respective receptors were compared to acetylcholine. RESULTS: Acetylcholine
      caused concentration-dependent phasic contractions in longitudinal and circular
      muscle of normal ileum and colon (both P < 0.01). In inflamed tissues,
      contractile responses were reduced to 17%-33% in ileum (P < 0.05) and 3%-26% in
      colon (P < 0.01). Both natural tachykinins and their specific analogs caused
      concentration-dependent phasic, tonic and rhythmic contractions (each P < 0.01).
      Neuropeptide gamma was most potent in contracting the ileum and colon, followed
      by neurokinin A, substance P and neurokinin B, let alone longitudinal muscle of
      the ileum where neuropeptide gamma and neurokinin A were equipotent. Of the
      tachykinin analogs, Nle10-NKA(4-10) was more potent than substance P methyl ester
      and senktide, indicating neurokinin 2 receptors are predominant for contractile
      effects of tachykinins. In inflamed tissues, contractile responses to tachykinins
      were reduced to 0%-42% in ileum (P < 0.05) and 0%-17% in colon (P < 0.01)
      compared to controls. CONCLUSION: In humans, tachykinins exert gut contractile
      effects, of similar strength as acetylcholine, predominantly through activation
      of neurokinin 2 receptors. These responses are greatly reduced in inflamed
      tissues of ulcerative colitis and Crohn disease.

PMID- 11346202
TI  - Morphological and functional abnormalities in the ileum of rats with spontaneous
      hypertension: studies on SGLT1 protein.
AB  - BACKGROUND: Na+-dependent D-glucose and D-galactose transport was studied in the
      ileal brush-border membrane vesicles from both spontaneously hypertensive rats
      (SHR) and their normotensive genetic control Wistar-Kyoto (WKY) rats. Initial
      rates and accumulation ratios of the transport of both monosaccharides were
      significantly lower in the hypertensive rats compared to the WKY rats. METHODS:
      In order to determine whether such modifications are related to morphological
      abnormalities, ileal epithelium of SHR and WKY rats was examined by light and
      electron microscopy. In addition, immunohistochemical and immunocytochemical
      localization of Na+-glucose cotransporter (SGLT1) was performed. RESULTS: Light
      microscopy studies showed hypertrophy in the ileal villi of hypertensive rats,
      with an increase in the villus width when compared to those from normotensive
      rats. Immunohistochemical studies of SGLT1 showed the protein localized in the
      apical membrane of the absorptive epithelial cells, along the entire villus. No
      changes between SHR and WKY rats were noted in the intensity and distribution of
      the SGLT1 protein along the villus-crypt axis. Electron microscopy studies showed
      a patchy loss of microvilli in the ileal enterocytes of SHR, compared to those
      from WKY rats. Immunocytochemical studies of SGLT1 were carried out by the
      immunogold method. Colloidal gold particles were localized at the ileal
      microvilli of normotensive rats. No significant presence of SGLT1 was found in
      the smooth apical surface of ileum from hypertensive rats, although most adjacent
      microvilli were marked. CONCLUSION: Morphological changes were accompanied by
      modifications in the sugar transport and in the immunolocalization of SGLT1 in
      the ileal epithelium of SHR.

PMID- 11346203
TI  - Anxiety but not depression decreases in coeliac patients after one-year gluten
      free diet: a longitudinal study.
AB  - BACKGROUND: A high prevalence of anxiety and depression has been reported in
      untreated coeliac disease (CD) patients. At present, the role of a gluten-free
      diet (GFD) on psychological disorders is still poorly known. The aim of this
      study was to evaluate state and trait anxiety and depression in adult CD patients
      before and after 1 year of GFD. METHODS: A total of 35 CD patients were studied
      before and after 1 year of GFD. A total of 59 healthy subjects matched for
      gender, age and socio-economic status were studied as a control group. State and
      trait anxiety were assessed with the STAI test; depression was assessed using the
      modified version of the SDS Zung self-rating depression scale (M-SDS). The tests
      were administered before (TO) and after 1 year of GFD (T1). RESULTS: At T0, CD
      patients showed high levels of state anxiety in a significantly higher percentage
      compared to controls (71.4% versus 23.7%; P < 0.0001), while there was no
      significant difference in trait anxiety between groups (25.7% versus 15.2%;
      P:ns); the percentage of subjects with depression was significantly higher in the
      CD group than in the control group (57.1% versus 9.6%; P < 0.0001). At T1, a
      significant decrease in the percentage of state anxiety was found in CD patients
      (T0: 71.4% versus T1: 25.7%; P < 0.001), while there were no significant changes
      in the percentage of trait anxiety (T0: 25.7% versus T1: 17.1%; P:ns) or
      depression (T0: 57.1.% versus T1: 45.7%; P:ns), which was still present in a
      significantly higher percentage in treated CD compared to controls (P < 0.0001).
      CONCLUSION: In CD patients anxiety is present in a predominantly reactive form
      and it decreases after GFD. Depression is present in a higher percentage in CD
      patients and 1 year of GFD fails significantly to affect depressive symptoms. The
      presence of depression after GFD could be related to the reduction in quality of
      life in CD patients. The non-regression of depression after GFD could suggest
      that these patients need psychological support.

PMID- 11346204
TI  - Duodenal disaccharidase activities in the follow-up of villous atrophy in coeliac
      disease.
AB  - BACKGROUND: In active coeliac disease, mucosal atrophy is associated with a
      marked decrease in intestinal disaccharidase enzyme activities. We investigated
      the value of duodenal mucosal disaccharidases to predict the severity of mucosal
      villous atrophy and its recovery in 50 patients with coeliac disease. METHODS:
      Duodenal mucosal histology and disaccharidase activities were studied at least
      twice with a mean interval of 9 months. Histology of specimens from all patients
      was examined by the same pathologist blinded to the data on disaccharidase
      activities. Mucosal damage was scored into four groups as follows: Grade 0 =
      normal mucosa; grade I = slight villous atrophy, that is, cryptic component 30%
      50%; grade 2 = moderate villous atrophy, that is, cryptic component 50%-90%;
      grade 3 = severe villous atrophy, that is, cryptic component >90%. The enzyme
      activities of the disaccharidases were determined as U/g protein. RESULTS:
      Duodenal mucosal disaccharidase activities were good predictors of the grade of
      mucosal villous atrophy. Positive predictive values for moderate or severe
      villous atrophy were 90% for maltase (maltase activity <150 U/g protein), 86% for
      sucrase (<40 U/g protein) and 71% for lactase (<20 U/g protein). Accordingly,
      negative predictive values, that is, none or only minimal villous atrophy (grades
      0 or 1) with normal disaccharidase activities, were 71% for maltase, 70% for
      sucrase and 63% for lactase. CONCLUSIONS: The increase in duodenal disaccharidase
      activities correlated with recovery of the mucosa based on histology. Besides the
      histological examination, measurement of disaccharidase activities offers an
      additional tool to evaluate response to a gluten-free diet in patients with
      coeliac disease.

PMID- 11346205
TI  - Sensitivity of serum tissue transglutaminase antibodies for endomysial antibody
      positive and negative coeliac disease.
AB  - BACKGROUND: Serum antibodies to tissue transglutaminase (tTGA) are reported to
      have high sensitivity and specificity for coeliac disease and to correlate
      closely with endomysial antibodies (EmA). We assessed their performance in a
      coeliac population with a high proportion of EmA-negative patients, who have been
      under-represented in previous studies. METHODS: We used a commercial ELISA kit to
      test for IgA class tTGA in sera from a population of 73 untreated coeliac
      patients with normal serum IgA and a high percentage (19%) EmA-negative, taking
      58 patients with normal duodenal biopsies as controls. EmA was measured using
      indirect immunofluorescence. RESULTS: Forty-six (63%) patients with villous
      atrophy (VA) had both tTGA and EmA. However, when considered separately,
      sensitivities of tTGA and EmA for VA were similar (75% versus 81%) and both had
      high specificity (98% versus 97%). As 9 patients were tTGA-positive only and 13
      had EmA only, selection of patients for biopsy on the presence of either antibody
      would have had a sensitivity of 93% (68 of 73), with 5 (7%) patients seronegative
      for both. CONCLUSION: Although the ELISA tTGA assay is more convenient than EmA
      testing, it offers no advantages in sensitivity or specificity if used in
      isolation. However, incomplete concordance between EmA and tTGA positivity means
      that combination screening with both assays offers higher sensitivity, as almost
      a third of patients have only one antibody. As some coeliac patients with normal
      serum IgA are negative for both antibodies, biopsies should still be performed in
      seronegative individuals deemed at high risk for coeliac disease.

PMID- 11346206
TI  - Increased serum levels of eotaxin in patients with inflammatory bowel disease.
AB  - BACKGROUND: The CC-chemokines eotaxin and eotaxin-2, produced by epithelial and
      phagocytic cells, are potent and selective chemoattractants for eosinophils and
      basophils. The eosinophil is a potent inflammatory cell thought to play an
      important role in the pathogenesis of inflammatory bowel disease (IBD). In this
      study we investigated the serum concentrations of eotaxin and eotaxin-2 in
      patients with Crohn disease and ulcerative colitis. METHODS: Thirty-one patients
      with Crohn disease, 35 patients with ulcerative colitis and 41 control patients
      were studied. Eotaxin and eotaxin-2 serum levels were measured with solid phase
      sandwich enzyme-linked immunosorbent assays. RESULTS: Significantly increased
      serum eotaxin levels were observed in both patients with Crohn disease (289.4+/
      591.5 pg/ml) and ulcerative colitis (207.0+/-243.4 pg/ml) when compared with
      controls (138.0+/-107.8 pg/ml) (P < 0.01). Moreover, patients with active Crohn
      disease and ulcerative colitis showed significantly higher serum eotaxin levels
      than patients with quiescent disease (434.0+/-776.8 pg/ml versus 113.8+/-65.4
      pg/ml in Crohn disease and 295.7+/-337.1 versus 121.2+/-91.9 pg/ml in ulcerative
      colitis, P < 0.05). In contrast, there was no significant difference in eotaxin-2
      serum levels among patients with Crohn disease (863.5+/-448.2 pg/ml), ulcerative
      colitis (1028.3+/-431.4 pg/ml) and controls (981.4+/-539.4 pg/ml). CONCLUSIONS:
      Eotaxin is significantly increased in serum of patients with active Crohn disease
      and ulcerative colitis, suggesting that this cytokine may play a role in the
      pathogenesis of IBD.

PMID- 11346207
TI  - Is an increased intestinal permeability a valid predictor of relapse in Crohn
      disease?
AB  - BACKGROUND: An increased intestinal permeability (IP) may be a pathogenetic
      factor in Crohn disease (CD). Increases in IP could be an indicator of
      subclinical disease and precede clinical relapses. We examined whether an
      increased IP is a valid predictor of relapse in CD. METHODS: 27 patients with CD
      in remission (CDAI <150) and 22 healthy controls ingested 3.7 MBq of 51Cr-EDTA,
      20 kBq of 14C-mannitol and 5 g of unlabelled mannitol in 100 ml of distilled
      water. The percent urine excretion (24 h) of labelled markers was determined.
      Patients were followed for 1 year or until relapse, defined as CDAI > 150 and >
      50 from baseline. RESULTS: Median (25th-75th percentiles). The excretion of 51Cr
      EDTA was 1.55% (1.13%-2.53%) for patients and 1.20% (1.11%-1.44%) for controls (P
      = 0.04). Three of 9 patients with a raised, and 6 of 18 patients with a normal,
      51Cr-EDTA excretion relapsed (P = 1.00; Fisher's exact test). Thus, the
      specificity and sensitivity of the 51Cr-EDTA test as a predictor of relapse was
      67% and 33%, respectively. The 51Cr-EDTA/14C-mannitol index was 0.060 (0.037
      0.093) for patients and 0.045 (0.038-0.054) for controls (P = 0.06). Four of 12
      patients with a raised, and 5 of 15 patients with a normal, index relapsed (P =
      1.00; Fisher's exact test). Thus, the specificity and sensitivity of the index
      test as a predictor of relapse was 56% and 44%, respectively. For controls and
      patients in remission, who were tested twice, variability of and fluctuations in
      both the 51Cr-EDTA excretion and the index were greatest for patients.
      CONCLUSIONS: This study supports previous findings of an increased IP in patients
      with CD. Although fluctuations in the permeation of markers were pronounced in
      CD, neither the excretion of 51Cr-EDTA nor the 51Cr-EDTA/14C-mannitol index test
      were valid predictors of relapse in CD.

PMID- 11346208
TI  - Tuberculosis in the belly: a review of forty-six cases involving the
      gastrointestinal tract and peritoneum.
AB  - BACKGROUND: Abdominal tuberculosis has varied presentation and can be confused
      with other conditions. METHODS: We report our experience with 46 patients. Charts
      of patients managed during 1984-97 were reviewed. RESULTS: Fifty-two percent were
      women and mean age was 46 years. Presenting symptoms were as follows: fever 70%;
      abdominal pain 70%; weight loss 68%; abdominal swelling 67%; change in bowel
      habit 39%; anorexia 30%; and sweating 30%. Common physical signs were as follows:
      fever 73%; ascites 61%; abdominal mass 13%; and doughy abdomen 9%. Thirty percent
      of patients either gave past history of TB or presented with active TB of other
      sites. TB skin test was positive in only 27% of patients. CT scans of abdomen
      were abnormal in 80%, showing ascites, peritoneal lesions or enlarged nodes.
      Ascitic fluid was diagnostic for TB on smear/culture in 33%. Peritoneal biopsy
      was performed by laparoscopy or laparotomy in 61%. It was positive for ganulomas
      in 97% and for smear/culture in 68%. Forty-two patients recovered after receiving
      anti-TB therapy for 9-12 months. Four patients died. One died within 1 month of
      initiation of therapy due to extensive TB, and death in the other 3 was due to
      unrelated causes. CONCLUSION: Abdominal TB should be suspected in patients with
      fever, abdominal pain and ascites. This condition carries good prognosis if
      promptly diagnosed and treated.

PMID- 11346209
TI  - Hydrophilic and hydrophobic bile acids exhibit different cytotoxicities through
      cytolysis, interleukin-8 synthesis and apoptosis in the intestinal epithelial
      cell lines. IEC-6 and Caco-2 cells.
AB  - BACKGROUND: Bile acids have been shown to exhibit varying degrees of
      cytotoxicity, depending on their hydrophobic-hydrophilic balance. We have
      recently reported the strong cytotoxicity of hyodeoxycholic acid (HDCA), and the
      aim of the present study is to investigate the mechanisms underlying the
      cytotoxicity of HDCA. METHODS: The intestinal cell lines IEC-6 and Caco-2 cells
      were used. The cytotoxicities of various bile acids were evaluated using the MTS
      assay; their cytolytic effects were measured using the LDH release assay. The
      induction of apoptosis was determined by the specific figure changes in the
      cellular cytoplasm and nucleus, including DNA ladder formations. IL-8 synthesis
      induced by the bile acids was measured using an ELISA assay. RESULTS: The bile
      acids induced cytotoxic effects, LDH release, IL-8 synthesis and apoptosis,
      depending on their hydrophobic properties. On the other hand, HDCA induced strong
      cytotoxicity, apoptosis and IL-8 synthesis but not cytolysis, although HDCA has a
      hydrophilic nature. In addition, HDCA exerted the strongest effects on dispersing
      monolayer cells. CONCLUSIONS: These results strongly suggest that HDCA induces
      cytotoxicity through its ability to induce apoptosis rather than its detergent
      effect.

PMID- 11346210
TI  - Role of gender upon basal and postprandial systemic and splanchnic haemodynamics
      in humans.
AB  - BACKGROUND: Food intake, accompanied by systemic and splanchnic haemodynamic
      changes, has only been studied in males. The extent to which splanchnic
      postprandial hyperaemia shows gender differences is unknown. METHODS: We tested
      1) the splanchnic hyperaemic response to food in females and 2) whether
      postprandial haemodynamic changes show gender differences. Twenty-four healthy
      women (aged 20-35 years) and 20 healthy men (aged 21-34 years) participated in
      the study. A liquid test meal (Ensure plus, 1.5 kcal/ml) was perfused
      intraduodenally for 75 min through an enteral feeding tube at a rate of 3 ml/min
      after a 45-min basal period. Blood flow parameters were measured using Echo
      Doppler technology. RESULTS: Basal diastolic arterial blood pressure was
      significantly (P < 0.05) lower in females (66+/-2 versus 72+/-2 mmHg), whereas
      heart rate was the same (58+/-2 b/min, ns). Postprandially, diastolic blood
      pressure fell, but reached significance only in males (-10+/-3 mmHg; P < 0.05).
      Mean velocity in the superior mesenteric artery (SMA) was significantly (P <
      0.05) higher in females compared to males at baseline (47+/-3 versus 39+/-2
      cm/s), whereas maximal postprandial changes were similar (64+/-6 versus 56+/-6
      cm/s, ns). Volume flow in the portal vein (PV) at baseline was 656+/-29 and 716+/
      35 ml/min females and males, respectively (ns between gender). Maximal
      postprandial changes amounted to 808+/-86 and 884+/-107 ml/min, respectively
      (ns). CONCLUSIONS: 1) Perfusion of a liquid test meal induces significant
      increases in flow parameters in the SMA and PV in both genders. 2) These changes
      are partly paralleled by alterations in systemic haemodynamics. 3) Postprandial
      splanchnic flow parameters are qualitatively and quantitatively not different
      between genders.

PMID- 11346211
TI  - Quality of life in patients with irritable bowel syndrome seen in referral
      centers versus primary care: the impact of gender and predominant bowel pattern.
AB  - BACKGROUND: Quality of life (QOL) is reduced in patients with irritable bowel
      syndrome (IBS) and little is known about differences in QOL in relation to
      referral status, gender and predominant bowel pattern in IBS patients. This study
      aimed to explore these relationships. METHODS: 343 patients with IBS according to
      the Rome I criteria (251 females, 92 males) completed five different self
      administered questionnaires to evaluate QOL. There were 119 patients with
      diarrhea-predominant IBS (IBS-D), 93 with constipation-predominant IBS (IBS-C)
      and 131 with alternating constipation and diarrhea (IBS-A). The study group
      comprised 209 hospital outpatients and 134 primary care patients. The
      questionnaires were mailed to the patients with an overall response rate of 88%.
      RESULTS: QOL was reduced in hospital outpatients compared to primary care
      patients, but only in females. IBS subgroup (IBS-D), physical fatigue and general
      health independently predicted referral to a gastroenterologist. Females had
      lower QOL than males. No differences, except in severity of diarrhea and
      constipation, were observed between IBS subgroups. Perceived fatigue was related
      to well-being, psychological and gastrointestinal symptoms. Independent
      predictors for fatigue were depression, trait anxiety, general health and
      vitality, along with eating dysfunction and female sex. CONCLUSION: IBS female
      patients seen in referral centers versus primary care is a highly selected group
      with reduced QOL. QOL in IBS is affected by gender, but not by subgroup. Our
      findings have implications for the generalizability of results in IBS trials.
      Fatigue is a common symptom in IBS that correlates to general well-being and
      psychological and subjective gastrointestinal symptoms.

PMID- 11346212
TI  - Evaluation of hepatobiliary function by hepatobiliary scintigraphy in hepatoma
      patients after transcatheter arterial embolization.
AB  - BACKGROUND: Transcatheter arterial embolization (TAE) is the treatment of choice
      for inoperable hepatocellular carcinoma. However, altered and impaired
      gallbladder function due to gallbladder infarction and bile duct necrosis
      following TAE have been reported. METHODS: Hepatobiliary function was evaluated
      using quantitative Tc-99m DISIDA hepatobiliary scintigraphy in 40 hepatoma
      patients before and after TAE. The patients were separated into two groups: group
      1 (20 patients), who received pre-cystic artery TAE, and group 2 (also 20
      patients), who received post-cystic artery TAE. RESULTS: After TAE, there were no
      significant changes in liver or bile duct function in the patients of either
      group. However, for group I patients, significantly decreased gallbladder
      function was found after TAE. CONCLUSIONS: Altered and impaired gallbladder
      function is common in hepatoma patients who receive pre-cystic artery TAE, and Tc
      99m DISIDA cholescintigraphy may be useful for evaluating hepatobiliary function
      in hepatoma patients who receive TAE.

PMID- 11346213
TI  - Autoimmune hypopituitarism in patients with coeliac disease: symptoms confusingly
      similar.
AB  - Coeliac disease does not always respond properly to a gluten-free diet, and
      treatment may be complicated by an underlying autoimmune endocrine disorder. We
      report three cases of hypopituitarism in patients with coeliac disease who seemed
      to have incomplete dietary response. The first patient had diabetes and suffered
      from hypoglygaemic events; the second had muscular atrophy of unknown origin
      while the third had growth failure. None had a pituitary mass, suggesting that
      hypopituitarism was of autoimmune origin. Overall condition improved only after
      replacement therapy for the underlying hormone deficiency; this association
      should thus be recognized.

PMID- 11346214
TI  - Sympathetic nervous system activation in essential hypertension, cardiac failure
      and psychosomatic heart disease.
AB  - Regional sympathetic activity can be studied in humans using electrophysiological
      methods measuring sympathetic nerve firing rates and neurochemical techniques
      providing quantification of noradrenaline spillover to plasma from sympathetic
      nerves in individual organs. Essential hypertension: Such measurements in
      patients with essential hypertension disclose activation of the sympathetic
      outflows to skeletal muscle blood vessels, the heart and kidneys, particularly in
      younger patients. This sympathetic activation, in addition to underpinning the
      blood pressure elevation, most likely also contributes to left ventricular
      hypertrophy, and to the commonly associated metabolic abnormalities of insulin
      resistance and hyperlipidaemia. Antihypertensive drugs, such as moxonidine, which
      act primarily by inhibiting the sympathetic nervous system, should have
      additional clinical benefits beyond those attributable to blood pressure
      reduction, in protecting against hypertensive complications. Obesity-related
      hypertension: Understanding the neural pathophysiology of hypertension in the
      obese has been difficult. In normotensive obesity, renal sympathetic tone is
      doubled, but cardiac noradrenaline spillover (a measure of sympathetic activity
      in the heart) is only 50% of normal. In obesity-related hypertension, there is a
      comparable elevation of renal noradrenaline spillover, but without suppression of
      cardiac sympathetics (cardiac sympathetic activity being more than double that of
      normotensive obese and 25% higher than in healthy volunteers). Increased renal
      sympathetic activity in obesity may be a 'necessary' cause for the development of
      hypertension (and predisposes to hypertension development), but apparently is not
      a 'sufficient' cause. The discriminating feature of the obese who develop
      hypertension is the absence of the adaptive suppression of cardiac sympathetic
      tone seen in the normotensive obese. Heart failure: In cardiac failure, the
      sympathetic nerves of the heart are preferentially stimulated. Noradrenaline
      release from the failing heart at rest in untreated patients is increased as much
      as 50-fold, similar to the level seen in the healthy heart during near-maximal
      exercise. Activation of the cardiac sympathetic outflow provides adrenergic
      support to the failing myocardium, but at a cost of arrhythmia development and
      progressive myocardial deterioration. Psychosomatic heart disease: No more than
      50% of clinical coronary heart disease is explicable in terms of classical
      cardiac risk factors. There is gathering evidence that psychological
      abnormalities, particularly depressive illness, anxiety states, including panic
      disorder and mental stress, are involved here, 'triggering' clinical
      cardiovascular events, and possibly also contributing to atherosclerosis
      development. The mechanisms of increased cardiac risk attributable to mental
      stress and psychiatric illness are not entirely clear, but activation of the
      sympathetic nervous system seems to be of prime importance.

PMID- 11346215
TI  - Mechanisms and clinical implications of blood pressure variability.
AB  - Several studies have unequivocally shown that the target-organ damage associated
      with the hypertensive condition is more closely related to 24 h average blood
      pressure values than to clinic blood pressure. Blood pressure, however, is highly
      variable over the daytime and night-time period, and of major interest is whether
      average 24 h blood pressure values, as well as 24 h blood pressure variability,
      correlate with, and are possibly responsible for, the hypertension-related
      alterations of the target-organ structure and function. This paper will address
      this issue by discussing the main features of blood pressure variability in
      hypertension. It will also examine the mechanisms involved in this phenomenon,
      with particular emphasis on the pathogenetic role of sympathetic neural factors.
      The clinical relevance of blood pressure variability in promoting target-organ
      damage, as well as its therapeutic implications, will finally be highlighted.

PMID- 11346216
TI  - Imidazoline receptors in cardiovascular and metabolic diseases.
AB  - The site of the hypotensive action of imidazoline compounds, such as clonidine,
      was first identified within the rostroventrolateral part of the brainstem.
      Afterwards, it was shown that imidazolines reduced blood pressure when applied in
      this area, whereas no catecholamine was capable of such an effect. These data led
      us to suggest the existence of receptors specific for imidazolines different from
      the alpha-adrenergic receptors. Soon after, the existence of imidazoline binding
      sites (IBS) was reported in the brain and in a variety of peripheral tissues
      including pancreatic gland and kidney. As expected, these specific binding sites
      do not bind the catecholamines. The IBS are classified in two groups: the I1
      type, sensitive to clonidine and idazoxan; and the I2 type, sensitive to idazoxan
      and largely insensitive to clonidine. Imidazoline receptors were shown to be
      involved in several physiological regulations and pathological processes such as
      hypertension, diabetes mellitus and some mood disorders. Evidence for their
      implication in the nervous regulation of blood pressure and in the insulin
      secretion control will be presented. The hypotensive effects of clonidine-like
      drugs involve imidazoline receptors (I1Rs), while their most frequent side
      effects only involve alpha2-adrenergic receptors. A new class of centrally acting
      antihypertensive drugs selective for I1Rs is now available. At hypotensive doses,
      these drugs are devoid of significant side effects. It was shown that the good
      acceptability of these drugs is likely due to their selectivity for I1Rs.

PMID- 11346217
TI  - Pharmacology of moxonidine: an I1-imidazoline receptor agonist.
AB  - The I1-imidazoline receptor is a novel neurotransmitter receptor found mainly in
      the brainstem, adrenal medulla and kidney. The actions of moxonidine are
      described at the level of individual biomolecules, cells, tissues, organs and
      finally with integrative functions. The receptor functions at the cellular level
      works through arachidonic acid and phospholipid signaling cascades in neuronal
      cells with the net result of inhibiting sympathetic premotor neurons.

PMID- 11346218
TI  - Antihypertensive drugs and the sympathetic nervous system.
AB  - The sympathetic nervous system (SNS) plays an important role in the regulation of
      blood pressure homeostasis and cardiac function. Furthermore, the increased SNS
      activity is a predictor of mortality in patients with hypertension, coronary
      artery disease and congestive heart failure. Experimental data and a few clinical
      trials suggest that there are important interactions between the main pressor
      systems, i.e. the SNS, the renin-angiotensin system and the vascular endothelium
      with the strongest vasoconstrictor, endothelin. The main methods for the
      assessment of SNS activity are described. Cardiovascular drugs of different
      classes interfere differently with the SNS and the other pressor systems. Pure
      vasodilators including nitrates, alpha-blockers and dihydropyridine (DHP)-calcium
      channel blockers increase SNS activity. Finally, central sympatholytics and
      possibly phenylalkylamine-type calcium channel blockers reduce SNS activity. The
      effects of angiotensin-II receptor antagonists on SNS activity in humans is not
      clear; experimental data are discussed in this review. There are important
      interactions between the pressor systems under experimental conditions. Recent
      studies in humans suggest that an activation of the SNS with pure vasodilators in
      parallel increases plasma endothelin. It can be assumed that, in cardiovascular
      diseases with already enhanced SNS activity, drugs which do not increase SNS
      activity or even lower it are preferable. Whether this reflects in lower
      mortality needs to be investigated in intervention trials.

PMID- 11346219
TI  - Moxonidine: a new and versatile antihypertensive.
AB  - Despite a proven efficacy in lowering blood pressure, centrally acting
      antihypertensive drugs are no longer widely used because of the relative high
      incidence of adverse effects. Most central side-effects occurring with these
      drugs are mediated by the alpha2-receptor. Moxonidine is an imidazoline receptor
      agonist that is highly selective for the I1-imidazoline receptor with little
      effect at the central alpha2-receptor. Moxonidine has been shown to diminish
      sympathetic activity, as measured by norepinephrine, epinephrine and plasma renin
      activity. Acute and long-term hemodynamic studies show that moxonidine reduces
      arterial pressure by lowering systemic vascular resistance while sparing heart
      rate, cardiac output and stroke volume. Moxonidine has been shown to reduce left
      ventricular hypertrophy and is metabolically neutral; it may have a favourable
      effect on insulin resistance. Clinical studies have documented efficacy of
      moxonidine as an antihypertensive agent. Most patients' blood pressure was
      satisfactorily controlled with a dose between 0.2 and 0.4 mg per day. Comparative
      studies are available with most other antihypertensive drug classes, such as
      clonidine, diuretics, alpha-blockers, beta-blockers, calcium antagonists, and ACE
      inhibitors, and document similar blood pressure control with moxonidine as with
      other agents. Specifically, by using 24-h ambulatory blood pressure monitoring,
      blood pressure control was found to be similar with moxonidine and enalapril. The
      side-effect profile of moxonidine has been shown to be favorable as might be
      expected from its lack of an alpha2-receptor mediated central effect. Moxonidine,
      therefore, represents an advance in the tolerability of anti-adrenergic drugs
      without apparent reduction in efficacy. All of these observations suggest that
      moxonidine may offer advantages over other antihypertensive drugs, but clearly
      these potential advantages need to be properly evaluated in a prospective
      morbidity and mortality study.

PMID- 11346220
TI  - Insulin resistance in chronic heart failure.
AB  - Insulin resistance is an important risk factor for the development of
      hypertension, atherosclerotic heart disease, left ventricular hypertrophy and
      dysfunction, and heart failure. It reflects a disturbance of glucose metabolism
      and potentially worsens metabolic efficiency of both skeletal muscle and cardiac
      muscle. The exact mechanisms of insulin resistance are not known, but the finding
      of significant insulin resistance occurring as a consequence of heart failure
      raises interesting possibilities as to its pathogenesis. While sympathetic
      nervous system overactivity can acutely reduce insulin sensitivity, it is not
      clear to what extent, in stable optimally treated chronic heart failure (CHF),
      the neurohormonal overactivity of this syndrome is the major cause of insulin
      resistance. Other potential mechanisms include the loss of skeletal muscle bulk,
      impaired endothelial function and reduced skeletal muscle blood flow, and a
      possible direct action of proinflammatory cytokines such as tumour necrosis
      factor-alpha. The consequences of insulin resistance in heart failure are not
      known, but the severity of the abnormality appears to parallel symptomatics and
      exercise limitation in this condition, and, in particular, be related to the
      impairment of gross skeletal muscle function. While specific therapies to correct
      insulin resistance in CHF have not been evaluated, there are several exciting
      possibilities on the horizon. Several nonpharmacological therapies have been
      shown to increase insulin sensitivity in patients with normal left ventricular
      function, and if these benefits could be duplicated in CHF, they may offer
      symptomatic benefit. These include weight reduction in the obese, regular
      exercise training and the use of dietary manipulation such as low-fat, high-fibre
      diets. Drug treatments with positive effects on insulin sensitivity include some
      angiotensin converting enzyme-inhibitors as well as newer drug groups, such as
      the glitazones and moxonidine, a centrally active agent with effects on the
      recently described imidazoline I-1 receptor that inhibits central sympathetic
      tone. The role of these agents in reversing the insulin resistance of chronic
      heart failure warrants further investigation.

PMID- 11346221
TI  - Endoscopic comparison of the gastroduodenal safety and the effects on arachidonic
      acid products between meloxicam and piroxicam in the treatment of osteoarthritis.
AB  - Our objective was to evaluate the efficacy, the gastroduodenal safety, and the
      effects on arachidonic acid products of meloxicam, a new acidic enolic non
      steroidal anti-inflammatory drug which preferentially inhibits cyclo-oxygenase-2
      over cyclo-oxygenase-1, versus piroxicam in patients with osteoarthritis of the
      knee. Meloxicam 7.5 mg or piroxicam 20 mg daily was administered for 4 weeks in
      this double-blind parallel-groups randomised study. The efficacy for pain relief
      of the two tested medications was assessed by means of visual analogue scale and
      other clinical parameters. Pre- and post-treatment endoscopies were performed,
      and the findings were scored and recorded. The gastric fluid was aspirated at
      each time and prostaglandin E2, thromboxane B2 and leukotriene B4 were determined
      by ELISA. There was no significant difference between the groups regarding the
      primary efficacy. Changes in endoscopic findings by means of Lanza score showed
      statistically significant differences between the two treatment groups in favour
      of meloxicam at all sites--gastric, duodenal and total. Within-group comparisons
      showed a statistically significant difference (worsening) in gastric and total
      score with piroxicam, but no significant difference with meloxicam. The frequency
      of clinically relevant cases (total score >2) also showed a statistically
      significant worsening in the piroxicam group. The better GI tolerability of
      meloxicam was also suggested by fewer adverse GI events and no withdrawals due to
      adverse events compared with piroxicam. The pre-/post-study gastric juice
      concentration of PGE2, TXB2, and LTB4 in the meloxicam group was 135.2 +/-
      85.8/71.2 +/- 32.2, 116.3 +/- 81.7/99.4 +/- 107.5 and 388 +/- 321/223 +/- 98
      pg/ml respectively. The pre-/post-study gastric juice concentration of PGE2, TXB2
      and LTB4 in the piroxicam group was 105.7 +/- 43.1/68.2 +/- 34.9, 94.0 +/-
      50.9/105.9 +/- 121.1 and 625 +/- 1574/828 +/- 1464 pg/ml, respectively. Both
      meloxicam and piroxicam significantly inhibited gastric PGE2 levels after 4
      weeks' treatment; however, there was no difference between these two groups.
      Neither of these medications had an effect on TXB2. Only meloxicam inhibited LTB4
      concentration significantly, and the between-groups difference was significant.
      Meloxicam 7.5 mg once daily had better gastrointestinal tolerability and an
      efficacy comparable to that of piroxicam 20 mg over 4 weeks in patients with
      osteoarthritis of the knee.

PMID- 11346222
TI  - Preventing recurrence of reflex sympathetic dystrophy in patients requiring an
      operative intervention at the site of dystrophy after surgery.
AB  - The development of reflex sympathetic dystrophy (RSD) is a common complication
      after surgery. Exacerbation or recurrence of RSD is a major concern after a
      second intervention at the site of previous surgery and consecutive RSD. It is
      unclear whether the risk of recurrent RSD can be reduced by using appropriate
      precautions. The objective of our study was to examine, in a case series of
      consecutive patients, whether recurrences in patients with a history of RSD after
      surgery, who were reoperated at the same location, can be avoided by using a
      standardised intervention protocol containing perioperative calcitonin
      prophylaxis. None of the patients experienced a recurrence of RSD. We concluded
      that the recurrence of RSD in patients requiring operative intervention at the
      site of former dystrophy after surgery appears to be unlikely with careful
      perioperative management.

PMID- 11346223
TI  - Cross-sectional study of 50 patients with calcium pyrophosphate dihydrate crystal
      arthropathy.
AB  - Calcium pyrophosphate dihydrate crystal arthropathy (CPPA) is a well known but
      heterogeneous disease with a variable presentation and course. We present a cross
      sectional study undertaken in a Portuguese rheumatology unit with the aim of
      analysing clinical and radiological patterns of CPPA in our population. The study
      population included 50 patients, 34 (68%) women and 16 (32%) men. The mean age
      was 69.8 +/- 8.8 years. The onset features were acute arthritis in 19 (38%)
      patients and chronic joint complaints in 26 (52%); five (10%) patients were
      asymptomatic at the time of diagnosis, which was based only on radiological
      findings. The diagnosis was established in 37 (74%) cases by clinical and
      radiographic features, in eight (16%) by clinical, X-ray and synovial fluid
      analysis, and in five (10%) by clinical features and fluid analysis. The disease
      course was characterised by acute episodic arthritis in 16 (32%) patients and by
      persistent symptoms (with or without synovitis) in 34 (68%). The pattern of CPPA
      in 20 (40%) patients was pseudo-osteoarthritis with synovitis, pseudo
      osteoarthritis without synovitis in nine (18%), pseudogout in nine (18%),
      monoarthropathy in eight (16%) and pseudorheumatoid arthritis in four (8%). The
      phosphocalcium balance was altered in nine (18%) cases: six patients had
      hypercalciuria two hyperphosphaturia, two hypocalciuria, one hypophosphaturia and
      one hypercalcemia. Five patients had abnormal thyroid hormone levels, but only
      one presented with clinical hypothyroidism. Four patients showed increased
      parathormone levels, but only one presented with clinical hyperparathyroidism.
      Radiographic findings showed that 43 (86%) patients had meniscus calcifications,
      20 (40%) radiocarpal and 16 (32%) calcification of the symphysis pubis. The study
      confirms the clinical variability of the disease in a population of Portuguese
      patients. The knee meniscus calcifications were the most sensitive single finding
      for establishing the diagnosis of CPPA. Almost all our patients had sporadic
      idiopathic CPPA without associated pathological conditions.

PMID- 11346224
TI  - Total mortality is increased in rheumatoid arthritis. A 17-year prospective
      study.
AB  - The purpose of this study was to determine the total and cause-specific mortality
      in rheumatoid arthritis (RA) patients compared to a control population in
      northern Norway. One hundred and eighty-seven patients with RA and 930 population
      controls matched for age, gender and municipality were followed until death or
      for a maximum of 17 years. The total mortality in RA patients was twice that of
      their controls (MRR = 2.0, 95% CI = 1.6-2.5). Patients possessing serum
      rheumatoid factors did not have a higher relative mortality than the seronegative
      patients. There was no statistically significant increased mortality from cancer
      or cardiovascular diseases. Indications for a higher death rate in RA patients
      than in controls were found for infection and sudden death.

PMID- 11346225
TI  - VATER association: is it recognised by rheumatologists?
AB  - The authors describe an adult patient with history of chronic low back pain and
      recurrent prostatitis, marked limitation of lumbar spine motion and a radiograph
      demonstrating fused lumbar vertebrae, which suggest a diagnosis of
      spondylarthropathy. However, the absence of radiographic evidence of sacroilitis,
      the nature of the vertebral defects and a history of imperforate anus pointed
      towards the diagnosis of VATER association, rather than a spondylarthropathy.
      Although most patients with VATER association are diagnosed during infancy, the
      musculoskeletal anomalies can be overlooked while the potentially life
      threatening problems are under treatment. These anomalies may become evident
      later in life. Therefore, in a rheumatologic practice, when evaluating patients
      with back pain and vertebral anomalies, one should become familiar with the
      varied manifestations of VATER association.

PMID- 11346226
TI  - Remitting seronegative symmetrical synovitis with pitting oedema in a patient
      with myelodysplastic syndrome and relapsing polychondritis.
AB  - Remitting seronegative symmetrical synovitis with pitting oedema (RS3PE) may be
      the inaugural manifestation of different rheumatic diseases of the elderly,
      malignancies and myelodysplastic syndromes (MDS). Relapsing polychondritis (RP)
      is a rare systemic disorder characterised by an inflammatory process involving
      predominantly cartilaginous structures, the cardiovascular system and organs of
      special sense. We report on a 72-year-old man with RS3PE and MDS, refractory
      anaemia subtype, diagnosed at the same time as RS3PE. Several months later the
      patient presented a clinical and pathological picture compatible with RP.
      Although the association between RP and MDS is well known, no previous cases of
      RS3PE preceding RP have been reported. This case confirms that RS3PE may herald
      many diseases, among others autoimmune disorders such as RP.

PMID- 11346227
TI  - Pachymeningitis and optic neuritis in rheumatoid arthritis: successful treatment
      with cyclophosphamide.
AB  - Pachymeningitis is a rare complication of rheumatoid arthritis. The case of a 52
      year-old male rheumatoid arthritis patient with pachymeningitis and optic
      neuritis who was successfully treated with intravenous cyclophosphamide is
      described.

PMID- 11346228
TI  - Coexistent Marfan's syndrome and ankylosing spondylitis: a case report.
AB  - We report on a 46-year-old man with a 4-year history of predominantly nocturnal
      pain at the thoracic and lumbar spine as well as accompanying morning stiffness
      and episodes of alternating buttock pain. At physical examination the patient
      presented with the typical traits for Marfan's syndrome (MFS), along with
      limitation of both chest expansion and movement in all planes of the lumbar
      spine. Pelvic and lumbar spine radiographs showed findings consistent with
      ankylosing spondylitis (AS). Laboratory tests were consistent with an
      inflammatory state and HLA typing was positive for the B27 antigen. Transthoracic
      echocardiography showed prolapse of the posterior mitral leaflet and mild aortic
      insufficiency. We diagnosed co-existent MFS and AS. The association of these two
      pathologies is particularly interesting, owing to the co-existence of
      hypermobility of peripheral joints due to MFS ligamentous hyperlaxity, and the
      reduction of both axial skeleton motility and chest expansion related to AS. As
      both of these diseases may damage the cardiovascular system over time, follow-up
      with echocardiography monitoring is indispensable.

PMID- 11346229
TI  - Painless destruction of the shoulder joint: a case report.
AB  - A case of painless destruction of the shoulder joint is reported for its rarity
      and unusual presentation as a neuroarthropathic joint with no evidence of
      neurological disease. A differential diagntosis of Gorham-Stout syndrome and
      avascular necrosis was discussed.

PMID- 11346230
TI  - Hypercalcaemia in systemic lupus erythematosus.
AB  - Hypercalcaemia is a common electrolyte abnormality. The vast majority of patients
      will be shown to have either hyperparathyroidism or malignancy. In less than 10%
      of patients other, less common causes of hypercalcaemia will be present. Systemic
      lupus erythematosus is a very rare cause of hypercalcaemia. It may be associated
      with lymphadenopathy and pleuritis to constitute a distinct clinical entity
      described as 'hypercalcaemia-lymphoedema syndrome'. In these cases the
      pathophysiology of the hypercalcaemia is not completely understood. In some cases
      it is associated with elevated levels of parathyroid-related peptide (PTHrP). In
      others the level of PTHrP is normal, and it has been suggested that
      autoantibodies may cause hypercalcaemia by activating the PTH receptor. We
      describe a case of a woman who presented with severe hypercalcaemia, developed
      the hypercalcaemia-lymphodema syndrome and fulfilled the diagnostic criteria of
      systemic lupus erythematosus.

PMID- 11346231
TI  - Fibromyalgia developed after administration of gonadotrophin-releasing hormone
      analogue.
AB  - We report the case of a woman treated with a gonadotrophin-releasing hormone
      analogue for endometriosis who developed typical clinical features of
      fibromyalgia, with widespread musculoskeletal pain, sleep difficulties,
      neuropsychological complaints and tender points on clininal examination. The
      gonadotrophin-releasing hormone analogue treatment probably induced disturbances
      in the neuroendocrine system and the secretion of neurotransmitters, and may be
      suspected to be the cause of this case of fibromyalgia.

PMID- 11346232
TI  - Renal involvement in juvenile rheumatoid arthritis: report of two cases.
AB  - Renal involvement is a rare occurrence in juvenile rheumatoid arthritis (JRA). We
      report on two JRA patients with kidney disease. The first was a 14-year-old
      African-American female with a 12-month history of polyarthritis. On presentation
      she was found to have an ESR of 127 mm/h and a positive ANA, rheumatoid factor
      (RF), perinuclear antineutrophil cytoplasmic antibodies (pANCA), haematuria,
      proteinuria with normal BUN and creatinine. Renal biopsy showed focal segmental
      glomerulosclerosis. Her renal function deteriorated to end-stage renal failure
      requiring dialysis within a few months, despite aggressive treatment with
      steorids and monthly i.v. pulses of cyclophosphamide. The second patient
      presented with a 6-week history of polyarthritis and intermittent fever, and had
      a salmon-coloured evanescent rash. On presentation his laboratory evaluation was
      significant for elevated ESR and negative ANA, RF and ANCA tests. Within 8 months
      the patient had developed a persistent microscopic haematuria. Renal biopsy
      showed mild mesangial glomerulonephritis. On low-dose methotrexate therapy his
      JRA went into remission and his renal function remained normal. The haematuria
      persisted for 1 year and then resolved spontaneously. This is the first time that
      focal segmental glomerulosclerosis and mesangial glomerulonephritis have been
      described in JRA. Although the association may be just coincidental, further
      studies are needed to define the role of JRA in these renal conditions. In
      patients with JRA, urinalysis and renal function should be routinely monitored.

PMID- 11346233
TI  - Antinuclear antibody (ANA) profile testing of ANA- positive patients.

PMID- 11346234
TI  - Primary meningococcal arthritis in the elderly.

PMID- 11346235
TI  - Mannitol treatment in central nervous system lupus.

PMID- 11346236
TI  - A preliminary study of circadian serum cortisol concentrations in response to a
      72-hour fast in rheumatoid arthritis patients not previously treated with
      corticosteroids.
AB  - The aim of the study was to investigate the effects a 72-h fast upon serum total
      and free cortisol concentrations in RA patients not previously treated with
      glucocorticoids. Total serum cortisol and transcortin concentrations were
      measured in four RA patients with active disease at 4-h intervals during two 24-h
      periods (1200 h-1200 h), the first while eating a normal diet (fed state) and the
      second during the last 24 h of a 72-h water fast. Free cortisol concentrations
      were calculated from the total cortisol and transcortin values. The 3-day fast
      increased overall 24-h free and total cortisol concentrations by 50% and 35%,
      respectively. This was due largely to a marked increase in nocturnal serum
      cortisol concentrations during fasting, particularly at 0400 h, when mean total
      and free cortisol levels were increased by 170% and 260% compared to the fed
      state. Between 2000 and 0800 h overall total- and free cortisol concentrations
      were increased by 72% and 99%, respectively. These results suggest that an
      increase in nocturnal concentrations of cortisol occurs in response to fasting in
      RA patients not previously treated with glucocorticoids. These increases may
      mediate the beneficial clinical response previously found in studies of longer
      fasting periods in RA patients.

PMID- 11346237
TI  - Prevalence of Raynaud's phenomenon in general practice in the east of Spain.
AB  - Our aim was to establish the prevalence of Raynaud's phenomenon in a general
      practice in the east of Spain and compare our results with those of other studies
      performed in geographical areas with similar climatic characteristics. Two
      hundred and seventy-six subjects visiting their general practitioner for whatever
      reason were randomly selected from a particular area of the city of Valencia.
      Each was interviewed by their GP following the guidelines of a structured
      questionnaire to establish whether they had Raynaud's phenomenon or not. There
      were 205 women and 71 men. The mean age was 54.43, with a standard deviation of
      18.22. Raynaud's phenomenon was present in nine subjects, two men and seven
      women, with a prevalence of 2.8% and 3.4%, respectively. Of the nine positives
      (mean age 60.56 years, standard deviation 16.38), two were diagnosed with
      hypertension and two with migraine. None of them usually took Raynaud's
      phenomenon-related drugs or performed physical exercise. No patient had a family
      history of Raynaud's phenomenon or had already been diagnosed with it. All the
      positive males were affected only by the pallor stage. This study shows lower
      prevalences than those of other studies performed in different geographical areas
      with similar climatic conditions.

PMID- 11346238
TI  - The characteristics of bronchoalveolar lavage from a patient with
      antiphospholipid syndrome who developed acute respiratory distress syndrome.
AB  - The purpose of this study was to investigate the biochemical characteristics as
      well as the occurrence and specificity of antiphospholipid antibodies in the
      bronchoalveolar lavage (BAL) fluid from a patient with both antiphospholipid
      antibodies syndrome (APS) and acute respiratory distress syndrome (ARDS).
      Proteins, lipids, cells and autoantibodies were determined. Immunoglobulins were
      purified with affinity chromatography. Autoantibody identification was assessed
      with enzyme-linked immunosorbent assay (ELISA) and with electrophoresis, followed
      by immunoblotting and revelation with antihuman IgG-peroxidase conjugate.
      Antiphospholipid antibodies were found to be present in the BAL fluid as well as
      in the serum from a patient with APS. Specifically, antiphosphatidylserine and
      antiphosphatidic acid IgG antibodies in the BAL fluid and antiphosphatidylcholine
      and anticardiolipin IgG antibodies in the serum were detected at high levels. BAL
      fluid protein and the percentage of neutrophils were found to be increased. A
      quantitative as well as qualitative deficiency of surfactant phospholipids was
      also observed. Antibodies directed against surfactant phospholipids could cause
      surfactant abnormalities and an inflammatory reaction. These disorders may be one
      of the causes of the ARDS or a factor in the perpetuation of the inflammation.

PMID- 11346240
TI  - Variability in response to thrombolytic therapy for acute ST-segment-elevation
      myocardial infarction.

PMID- 11346239
TI  - Intra-articular hyaluronic acid following knee immobilisation for 6 weeks in
      rabbits.
AB  - Thirty-two mature female New Zealand White rabbits were immobilised in an
      aluminium splint on one knee, using the contralateral non-treated knee as
      control. After 6 weeks the splints were removed and the rabbits allowed
      unrestricted movement. On a random basis, 16 rabbits were given an intra
      articular injection of 5 mg in 0.5 ml of hyaluronic acid (HA) in the knee of the
      immobilised hindlimb at weekly intervals for 6 weeks, starting 1 week after the
      joint had been remobilised, for a total of six injections. In the other 16
      rabbits no further intervention was conducted. At the end of the experiment the
      rabbits were killed, the area of degenerated joint surface of the distal femur,
      and water and proteoglycan content were measured, and the articular cartilage
      stained with haematoxylin and eosin and safranin O. Remobilisation without HA
      administration resulted in a significantly larger degenerated joint surface area.
      By the end of the experiment both remobilisation and remobilisation and intra
      articular HA injections had produced a greater but non-significant water
      cartilage content compared to the control side. The average cartilage
      glycosaminoglycan content of the remobilisation and intra-articular HA injection
      group was significantly greater than in the remobilisation group. In conclusion,
      in the rabbits with one knee immobilised for 6 weeks, 6 weeks of remobilisation
      alone are not sufficient to recover from the moderate articular surface changes
      produced, and the intra-articular administration of HA may produce a
      morphologically and biochemically more normal cartilage. More extensive animal
      and human studies should be performed before the routine use of intra-articular
      administration of HA following musculoskeletal injuries that required
      immobilisation can be recommended.

PMID- 11346241
TI  - Targeting patients with atrial fibrillation and improving their anticoagulation
      management.

PMID- 11346242
TI  - Transluminal endovascular stent grafting of aortic dissections and aneurysms: a
      concise review of the major trials.
AB  - Transluminal endovascular repair of the vascular system is rapidly emerging as a
      leading therapeutic modality for aortic dissections and aneurysms. The use of
      transluminal endovascular stent grafting has been used to intervene successfully
      on the aorta and its major branch vessels. There have been several studies
      examining transluminal endovascular stent grafting of thoracic aortic aneurysms,
      dissections, and abdominal aortic aneurysms. This paper reviews some of the major
      trials of transluminal endovascular stent grafting as well as its major
      limitation, endoleak.

PMID- 11346243
TI  - Preinfarction angina prevents left ventricular remodeling in patients treated
      with thrombolysis for myocardial infarction.
AB  - BACKGROUND: It has been shown that preinfarction angina may have beneficial
      effects on infarct size and mortality. However, there are no studies that have
      serially assessed the impact of preinfarction angina on left ventricular (LV)
      function in a large series of patients. HYPOTHESIS: The study was undertaken to
      determine whether preinfarction angina (within 7 days before infarction)
      influences LV remodeling. METHODS: In all, 119 consecutive patients with acute
      myocardial infarction were serially evaluated by 2-dimensional echocardiography
      (on Days 1, 2, 3, and 7; at 3 and 6 weeks; and at 3, 6, and 12 months following
      infarction). Left ventricular volumes were determined using Simpson's biplane
      formula and normalized for body surface area. Wall motion score index and
      sphericity index were calculated for each study. Coronary angiography was
      performed before discharge. RESULTS: Preinfarction angina was detected in 39 of
      119 patients. Initial echocardiographic and clinical data as well as the
      incidence of patent infarct-related artery and collaterals were similar for
      patients with and without preinfarction angina. In the subset of thrombolysed
      patients, patients with preinfarction angina showed decrease of LV end-diastolic
      and end-systolic volumes during the follow-up period (p = 0.033 and p = 0.001,
      respectively), and improvement of wall motion score index (p < 0.001) and
      ejection fraction occurred (p = 0.001), without changing of LV shape (p > 0.05);
      in addition, patients with preinfarction angina had smaller LV volumes and higher
      ejection fraction than did those without angina, from 3 weeks onward. These
      favorable effects were not detected in patients not treated with thrombolysis.
      CONCLUSIONS: These data indicate that preinfarction angina has an inhibiting
      effect on long-term LV remodeling in patients who underwent thrombolysis for
      first acute myocardial infarction. It appears that preinfarction angina has no
      impact on infarct size and early postinfarction LV function.

PMID- 11346244
TI  - Prognostic significance of bundle-branch block in acute myocardial infarction:
      the importance of location and time of appearance.
AB  - BACKGROUND: The presence of bundle-branch block (BBB) is associated with high
      mortality rates and is considered an important predictor of poor outcome in
      patients with acute myocardial infarction (AMI). HYPOTHESIS: The objective of
      this study was to assess the prognostic significance of BBB in patients with AMI
      depending on its form of presentation. METHODS: A multicenter prospective 1-year
      follow-up study involving 1,239 consecutive patients diagnosed with AMI was
      performed. RESULTS: Bundle-branch block was present in 177 cases (14.2%),
      associated with worse clinical characteristics, lower rate of thrombolytic
      therapy, and higher mortality: in-hospital (23.8 vs. 9.7%, p < .01) and 1-year
      (40.9 vs. 16.9%, p < 0.01). Compared with right BBB (n = 135), left BBB (n = 42)
      was more often associated with female gender and higher prevalence of
      cardiovascular diseases, but had a similar 1-year mortality. In the absence of
      heart failure or complete atrioventricular (AV) block, there was no difference in
      in-hospital mortality of patients with BBB (n = 76) and without BBB (n = 786)
      (2.6 vs. 3.9%). Compared with existing BBB (n = 113), BBB of new appearance (n =
      64) was more often accompanied by complete AV block and heart failure and higher
      in-hospital and 1-year mortality rates. Only BBB of new appearance was an
      independent predictor of mortality: in-hospital (odds ratio [OR] 2.3, 95%
      confidence interval [CI] 1.1-4.7) and 1-year mortality (OR 3.2, 95% CI, 1.7-9.1).
      CONCLUSIONS: In patients with AMI, the classification of BBB according not only
      to location but also to time of appearance is of practical interest. New BBB is
      an independent predictor of short- and long-term mortality.

PMID- 11346245
TI  - Increased levels of plasma thrombomodulin in patients with acute myocardial
      infarction who had thrombolytic therapy and achieved successful reperfusion.
AB  - BACKGROUND: There is a growing body of evidence from animal and in vitro studies
      for the existence of reperfusion injury after thrombolytic therapy for acute
      myocardial infarction (AMI), but the patient data are limited. HYPOTHESIS: We
      aimed to examine the plasma thrombomodulin (TM) levels as a marker of endothelial
      injury and to investigate the effect of successful reperfusion on these levels.
      METHODS: The study included 32 patients who had a first episode of acute
      myocardial infarction (AMI) and received intravenous streptokinase therapy.
      RESULTS: Thrombomodulin levels increased significantly at 60 min after
      thrombolysis compared with the levels before thrombolytic therapy (0 min) in 21
      (66%) patients who had successful reperfusion (49.09 +/- 10.51 vs. 25.76 +/- 5.55
      ng/ml, p < 0.001). There was no difference between the TM levels at 0 and at 60
      min of thrombolysis in the remaining 11 (34%) patients who could not achieve
      reperfusion (27.81 +/- 6.32 vs. 28.72 +/- 7.28 ng/ml, p = 0.35). CONCLUSION:
      There was a significant increase in TM levels at 60 min after thrombolysis in a
      group of patients with AMI who achieved successful reperfusion; this increase may
      have been caused by the activation/injury of endothelial cells. Data also suggest
      that the increment in TM levels may be predictive of the potential success of
      thrombolytic therapy.

PMID- 11346246
TI  - Adequacy of anticoagulation in patients with atrial fibrillation: effect of
      various parameters.
AB  - BACKGROUND: Despite reported evidence of the vital importance of appropriate
      anticoagulation in patients with chronic atrial fibrillation for stroke
      prevention, this treatment modality still lags behind optimal requirements.
      HYPOTHESIS: Our objectives were to evaluate various doctor or patient-related
      factors that influence quality of control and to assess the adequacy of
      anticoagulation provided by physicians in the community. METHODS: In a
      retrospective study, International Normalized Ratio (INR) values obtained
      immediately on admission to hospital were considered representative of previous
      long-term control. RESULTS: Only 42% of the relevant 385 patient population fell
      within the protective anticoagulation range of INR 1.91-4.1. The respective
      figures for patients with poor (INR < 1.5) or suboptimal (INR 1.51-1.9) control,
      as well as those whose INR values risked bleeding (INR > 4.1), were 28.3, 14.1,
      and 15.6%. Patient involvement in treatment positively influenced quality of
      control. By contrast, age 70-80 years or absence of congestive heart failure
      negatively affected quality of anticoagulation [p = 0.07, odds ratio (OR), 1.7
      (95% confidence interval. 0.94-3.08), p = 0.014, OR, 2.06 (95% confidence
      interval, 1.15-3.7) respectively]. The percentage of patients admitted with
      stroke who had been adequately anticoagulated was significantly lower than that
      of patients who had no stroke (21 vs. 44.4%). Adequacy of anticoagulation in
      patients with cardiac prosthetic valves was superior compared with the rest of
      the patient population (56.7 vs. 42% with optimal, and only 14.5 vs. 28.3% with
      poor anticoagulation, respectively), indicating that under the same conditions a
      better quality of treatment could be achieved. CONCLUSIONS: Adequacy of
      anticoagulation in patients with atrial fibrillation lags behind actual
      recommendations. Better control is required and achievable.

PMID- 11346247
TI  - Staged revascularization in critically ill patients with coronary artery disease.
AB  - BACKGROUND: Critically ill patients undergoing bypass surgery experience a higher
      mortality and morbidity. HYPOTHESIS: The study was undertaken to evaluate the
      efficacy and value of percutaneous transluminal coronary angioplasty (PTCA) as a
      bridge to coronary artery bypass graft surgery (CABG) in high-risk patients with
      refractory unstable angina or cardiogenic shock. METHODS: We present 11 seriously
      unstable patients with severe multivessel coronary artery disease undergoing
      culprit vessel PTCA. Angioplasty was performed not as a definitive procedure but
      rather as a bridge to surgical revascularization. All the patients had sustained
      at least one myocardial infarction prior to catheterization, all had refractory
      unstable angina, eight patients had only a single patent coronary artery, and
      five patients were in cardiogenic shock. RESULTS: Following PTCA, all patients
      enjoyed a stable in-hospital period. One patient died 12 weeks after successful
      PTCA while awaiting second CABG. Seven patients subsequently underwent CABG and
      are doing well. The remaining three patients were also advised to undergo CABG,
      but elected to continue medical management. CONCLUSIONS: Coronary angioplasty of
      the culprit vessel may play a role as a bridge to surgery in critically ill
      patients.

PMID- 11346248
TI  - Cardiac troponin T Arg92Trp mutation and progression from hypertrophic to dilated
      cardiomyopathy.
AB  - BACKGROUND: Mutations in the cardiac troponin T gene causing familial
      hypertrophic cardiomyopathy (HCM) are associated with a very poor prognosis but
      only mild hypertrophy. To date, the serial morphologic changes in patients with
      HCM linked to cardiac troponin T gene mutations have not been reported.
      HYPOTHESIS: The aim of this study was to determine the long-term course of
      patients with familial HCM caused by the cardiac troponin T gene mutation,
      Arg92Trp. METHODS: In all, 140 probands with familial HCM were screened for
      mutations in the cardiac troponin T gene. RESULTS: The Arg92Trp missense mutation
      was present in 10 individuals from two unrelated pedigrees. They exhibited
      different cardiac morphologies: three had dilated cardiomyopathy-like features,
      five had asymmetric septal hypertrophy with normal left ventricular systolic
      function, one had electrocardiographic abnormalities without hypertrophy, and one
      had the disease-causing mutation but did not fulfill the clinical criteria for
      the disease. The mean maximum wall thickness was 14.1 +/- 6.0 mm. The three
      patients with dilated cardiomyopathy-like features had progressive left
      ventricular dilation. Three individuals underwent right ventricular
      endomyocardial biopsy. There was a modest degree of myocardial hypertrophy
      (myocyte diameter: 18.9 +/- 5.2 microm), and minimal myocardial disarray and mild
      fibrosis were noted. CONCLUSION: The Arg92Trp substitution in the cardiac
      troponin T gene shows a high degree of penetrance, moderate hypertrophy, and
      early progression to dilated cardiomyopathy in Japanese patients. Early
      identification of individuals with this mutation may provide the opportunity to
      evaluate the efficacy of early therapeutic interventions.

PMID- 11346249
TI  - Thrombopoietin and mean platelet volume in coronary artery disease.
AB  - BACKGROUND: Large platelets are shown to be hemostatically more active. It has
      been suggested that mean platelet volume (MPV) is increased during acute
      myocardial infarction (AMI) and unstable angina pectoris (USAP). However, the
      underlying mechanism of the phenomenon remains unclear. HYPOTHESIS: In this
      study, platelets, MPV, and thrombopoietin (TP) levels were investigated in
      patients with coronary artery disease (CAD) and healthy controls. METHODS: Twenty
      patients with AMI and 20 patients with USAP were included in this study.
      Seventeen healthy adult subjects served as controls. Venous blood samples of the
      subjects were drawn within 12 h after admission. Thrombopoietin levels were
      measured by ELISA and platelet counts and MPV were assayed by autoanalyzer.
      RESULTS: Patients with AMI and USAP had higher platelet counts than those in the
      control group. Although the platelet counts were slightly higher in AMI than in
      USAP, this did not reach statistical significance. Mean platelet volume and
      levels of TP were found to be elevated in patients with AMI and USAP compared
      with control subjects (p < 0.001). Thrombopoietin levels were higher in AMI than
      USAP, but this was not statistically significant. There was a positive
      correlation between TP levels and MPV values (p < 0.05). CONCLUSION: Increased TP
      levels may increase both platelet counts and platelet size, resulting in
      hemostatically more active platelets, which may contribute to the development and
      progression of CAD.

PMID- 11346250
TI  - Effect of acute exercise on the raised plasma fibrinogen, soluble P-selectin and
      von Willebrand factor levels in chronic atrial fibrillation.
AB  - BACKGROUND: There is increasing evidence that chronic atrial fibrillation (AF) is
      associated with a prothrombotic or hypercoagulable state. HYPOTHESIS: This study
      was undertaken to determine whether short-term exercise in patients with chronic
      AF would shift the overall hemostatic balance toward a more prothrombotic state
      with a reduction in fibrinolytic potential. METHODS: We recruited 20 patients (13
      men; mean age 65 years +/- 11 standard deviation [SD]) with chronic AF who were
      not treated with antithrombotic therapy and exercised them to exhaustion using a
      multistage treadmill exercise (standard Bruce) protocol. Blood samples were taken
      pre exercise, immediately after cessation of exercise, and at 20 min post
      exercise. The prothrombotic state was quantified by fibrinogen (an index of
      hemorheology and a coagulation factor), soluble P-selectin (sP-sel, marking
      platelet activation), von Willebrand factor (vWF, an index of endothelial
      dysfunction), and plasminogen activator inhibitor-1 (PAI-1, a regulator of
      fibrinolytic activity) levels. There were two groups of age- and gender-matched
      controls in sinus rhythm: (1) healthy controls, and (2) "hospital controls" who
      were patients with vascular disease. RESULTS: Baseline levels of vWf (p = 0.034)
      and fibrinogen (p < 0.0001), but not sP-sel (p = 0.075) were significantly
      elevated in patients with AF compared with both control groups in sinus rhythm.
      The PAI-1 levels were highest in the hospital control patients, but not in
      chronic AF (p = 0.041). Following treadmill exercise, achieving a mean metabolic
      equivalent of 4.9 METS (+/- 1.75 SD) and total exercise duration of 4.9 min (+/-
      2 SD), there was a significant rise in plasma fibrinogen (repeated measures
      analysis of variance [ANOVA] p = 0.047) and a reduction in PAI-1 levels (p =
      0.025) in patients with AF. There were no significant changes seen in vWf (p =
      0.308) or sP-sel (p = 0.071) levels. No significant changes in these indices were
      seen in hospital controls (all p = not significant), despite a much longer
      duration of exercise with greater workload. CONCLUSION: Patients with chronic AF
      have increased vWf and fibrinogen levels compared with sinus rhythm. Exercise to
      exhaustion influences the hypercoagulable state in chronic AF, with a rise in
      plasma fibrinogen and possible increase in fibrinolytic activity. Nevertheless,
      acute exercise does not appear to have a significant influence on endothelial
      dysfunction or platelet activation in patients with AF.

PMID- 11346251
TI  - Images in cardiology. Chronic tuberculous pericarditis causing constrictive
      pericarditis.

PMID- 11346252
TI  - Diagnostic superiority of continuous-loop electrocardiographic recording over
      other testing in a patient with recurrent syncope and underlying coronary artery
      disease with severe left ventricular dysfunction.
AB  - Dysrhythmic causes of syncope may elude diagnosis in postinfarction patients
      despite elaborate testing, including electrophysiologic study. For a correct
      diagnosis, capture of cardiac rhythm during patient's typical symptoms is
      crucial. This report describes a patient with coronary artery disease and
      decreased left ventricular ejection fraction who experienced recurrent syncopal
      episodes without obvious precipitating factors. The 12-lead electrocardiogram
      showed left bundle-branch block indicating a possible conduction abnormality as
      the underlying cause of syncope. Twenty-four-h Holter monitoring exhibited no
      sinus rhythm or conduction disturbances but revealed a nonsustained run of
      ventricular tachycardia. Findings at electrophysiologic testing led to a
      presumptive diagnosis of tachyarrhythmic cause of syncope; however, the correct
      diagnosis was only made with use of a loop monitor which documented a 15-s sinus
      pause during a syncopal episode.

PMID- 11346253
TI  - Electrocardiographic criteria for predicting total occlusion of the proximal left
      anterior descending coronary artery in anterior wall acute myocardial infarction.

PMID- 11346255
TI  - Relationships among scrotal and testicular characteristics, sperm production, and
      seminal quality in 129 beef bulls.
AB  - Standard breeding soundness examinations plus measurement of scrotal surface
      temperature (SST), internal/scrotal testicular temperatures, testicular
      ultrasonographic echotexture, daily sperm production, and epididymal sperm
      reserves were conducted on 129, 16-month-old crossbred beef bulls. There were
      significant positive linear correlations between SST and internal
      scrotal/testicular temperatures, a positive linear regression (P < 0.06) of
      bottom SST with the incidence of secondary sperm defects, but a negative linear
      regression (P < 0.01) with the incidence of primary sperm defects. Testicular
      echotexture had a positive linear regression with daily sperm production (P <
      0.002) and testicular tone had a negative linear regression (P < 0.008) with
      epididymal sperm reserves. Scrotal circumference had a positive linear regression
      (P < 0.04) with the percentage of progressively motile sperm, a negative linear
      regression (P < 0.1) with the incidence of primary sperm defects, and a positive
      linear regression (P < 0.0001) with epididymal sperm reserves. In addition to
      seminal quality and scrotal circumference, testicular ultrasonographic
      echotexture has considerable promise for augmenting breeding soundness
      examinations of bulls.

PMID- 11346254
TI  - The failure of selenium supplementation to prevent copper-induced liver damage in
      Fischer 344 rats.
AB  - This study evaluates the ability of selenium (Se) supplementation to prevent
      experimental copper (Cu)-induced hepatocellular damage. Weanling male Fischer 344
      rats were randomly assigned to groups of 15, 3 groups (A,B,C) were fed Cu-loaded
      diets (containing 2000 microg/g copper, added as CuSO4) and different levels of
      Se (added as Na2SeO3 x 5H2O) as follows: A) Cu-loaded/Se adequate diet (0.4
      microg/g Se, fed basis); B) Cu-loaded/Se-supplemented diet (2 microg/g Se); and
      C) Cu-loaded/Se-deficient diet (< 0.2 microg/g). Three additional groups (D,E,F)
      were fed diets containing adequate levels of Cu (14 microg/g Cu, fed basis) and
      different levels of Se as follows: D) Cu-adequate/Se-adequate diet; E) Cu
      adequate/Se-supplemented diet (2 microg/g Se); and F) Cu-adequate/Se-deficient (<
      0.2 microg/g) diet. After 4, 8, and 12 weeks on the experimental diets, liver
      samples were processed for histology, histochemistry, metal analysis, glutathione
      peroxidase (GSH-Px) measurement, and quantification of malondialdehyde (MDA).
      Morphologic changes characteristic of Cu-associated hepatitis, without an
      increase in hepatic MDA levels, were seen in all Cu-loaded rats in each sampling.
      Similar changes occurred in rats fed Se-adequate, Se-supplemented and Se
      deficient diets. This study demonstrates that Fischer 344 rats fed 2000 microg/g
      Cu develop morphologic changes due to Cu toxicity without evidence of lipid
      peroxidation. Furthermore, Se supplementation does not result in protection
      against Cu-induced liver injury.

PMID- 11346256
TI  - The effects of atropine and methotrimeprazine on the epinephrine-induced
      arrhythmias in halothane-anesthetized dogs.
AB  - The effects of atropine and methotrimeprazine on epinephrine-induced ventricular
      arrhythmias were evaluated in halothane-anesthetized dogs. Ten mixed-breed dogs
      were assigned to 3 treatments (saline, atropine, and methotrimeprazine) in a
      randomized complete block design. Anesthesia was induced and maintained with
      halothane (1.5 minimum alveolar concentration) in oxygen. Controlled ventilation
      was used throughout to maintain eucapnia. Saline, atropine (0.05 mg/kg, i.v.) or
      methotrimeprazine (0.5 mg/kg, i.v.) were administered and, 5 minutes later the
      arrhythmogenic dose of epinephrine (ADE) was measured by i.v. infusion of
      progressively increasing infusion rates of epinephrine, until the ventricular
      arrhythmia criterion was met (at least 4 ectopic ventricular contractions (EVCs)
      during a 15-second period). Data were analyzed using a student's t-test for ADE
      values and multivariate profile analysis for heart rate (HR), arterial blood
      pressure (ABP), and rate pressure product (RPP). The ADE increased in atropine-
      and methotrimeprazine-treated groups, whereas 1 and 4 animals from these groups
      did not develop any ventricular arrhythmia, respectively. Epinephrine induced
      multiform premature ventricular contractions (PVCs) in the atropine group,
      whereas ventricular escape beats were observed in the control and
      methotrimeprazine groups. Heart rate and RPP decreased, and ABP increased at the
      time of ADE observation in the control group. Epinephrine infusion in the
      atropine group caused marked increases in HR, ABP, and RPP, which were associated
      with pulsus alternans in 2 animals. It was concluded that 1) the presence of
      cholinergic blockade influences the type of ventricular arrhythmia induced by
      epinephrine; 2) increased ADE values recorded following atropine administration
      must be cautiously interpreted, since in this situation the PVCs were associated
      with signs of increased myocardial work and ventricular failure; and 3) the use
      of a broader arrhythmia criterion (EVCs instead of PVCs) may not allow a direct
      comparison between ADE values, since it includes ventricular arrhythmias mediated
      by different mechanisms.

PMID- 11346257
TI  - Effects of dietary protein on glomerular mesangial area and basement membrane
      thickness in aged uninephrectomized dogs.
AB  - The primary objective of this study was to determine the effects of diets
      containing 18% or 34% protein on glomerular mesangial area (GMA) and basement
      membrane thickness (GBMT) in uninephrectomized aged dogs. A secondary objective
      was to determine the combined effects of aging and uninephrectomy on GMA and GBMT
      in dogs. Ten clinically healthy, pure-bred dogs were unilaterally nephrectomized
      at about 8 y of age. After 2 mo, 5 dogs were fed an 18% protein diet and 5 dogs
      were fed a 34% protein diet for 48 mo. At month 48, the dogs were euthanized and
      the remaining kidney was collected. Samples of kidney from both times of
      collection were used to measure GMA and GBMT using electron microscopy. The
      effects of diet on GMA and GBMT were analyzed (student's t-test) using
      necropsy/nephrectomy score ratios. The effects of time-nephrectomy were
      determined by comparing nephrectomy values for GMA and GBMT with necropsy values
      (paired t-test). Dogs fed 34% dietary protein did not have a significant increase
      in GMA and GBM thickness when compared to dogs fed the 18% protein diet. A
      significant increase in GMA and GBMT occurred with time-nephrectomy (P = 0.011
      and 0.018, respectively). Although dietary protein intake was not a significant
      factor in causing structural changes to glomeruli in uninephrectomized aged dogs,
      the power to detect a difference was low. However, significant effects of aging
      and nephrectomy were detected despite the low power of the study. These results
      suggest that the increases in GMA and GBMT that occur over time are not markedly
      influenced by dietary protein intake. However, subtle protein effects cannot be
      eliminated as a possibility based on this study.

PMID- 11346258
TI  - Resistance of cattle to scrapie by the oral route.
AB  - Early epidemiological information indicated that bovine spongiform encephalopathy
      (BSE) originated from scrapie in sheep. The question arose if scrapie in North
      America would induce a BSE-like disease in cattle. Six years ago, we reported
      that brain tissue from sheep with scrapie caused a neurologic disease when
      injected directly into the brains of cattle, but the disease induced was
      different from BSE as it occurs in the United Kingdom and Europe. Here, we report
      that cattle fed raw brain or meat and bone meal and tallow prepared from sheep
      with scrapie remained normal for 8 years after exposure. This work indicates that
      cattle are highly resistant to North American scrapie by the oral route.

PMID- 11346259
TI  - Quantitation of adenine nucleotides in equine colonic mucosal tissue using high
      performance liquid chromatography.
AB  - The objectives were to use high performance liquid chromatography (HPLC) to
      validate an established method for adenine nucleotide separation in equine
      colonic mucosal tissue, to determine the inherent variability in the tissue and
      extraction method, and to determine the stability of ATP, ADP, and AMP in the
      tissue with time. Equine colonic mucosal tissue obtained from a single horse was
      immediately submersed in liquid nitrogen, and stored at -70 degrees C. Samples
      were lyophilized, extracted, and separated by HPLC. The limit of quantitation was
      0.05 microg/mL. The coefficient of variation for the instrument was less than 10%
      for all nucleotides measured. When the tissue was not homogenized prior to
      sampling, there were significant differences in adenine nucleotide content
      between samples. However, when the tissue was homogenized prior to analysis,
      these differences were no longer significant. There was no significant decrease
      in ATP, ADP, or AMP content over a 54-day analysis period.

PMID- 11346260
TI  - Identification of a mutant bovine herpesvirus-1 (BHV-1) in post-arrival outbreaks
      of IBR in feedlot calves and protection with conventional vaccination.
AB  - Outbreaks of infectious bovine rhinotracheitis (IBR) have recently been observed
      in vaccinated feedlot calves in Alberta a few months post-arrival. To investigate
      the cause of these outbreaks, lung and tracheal tissues were collected from
      calves that died of IBR during a post-arrival outbreak of disease. Bovine
      herpesvirus-1 (BHV-1), the causative agent of IBR, was isolated from 6 out of 15
      tissues. Of these 6 isolates, 5 failed to react with a monoclonal antibody
      specific for one of the epitopes on glycoprotein D, one of the most important
      antigens of BHV-1. The ability of one of these mutant BHV-1 isolates to cause
      disease in calves vaccinated with a modified-live IBR vaccine was assessed in an
      experimental challenge study. After one vaccination, the majority of the calves
      developed humoral and cellular immune responses. Secondary vaccination resulted
      in a substantially enhanced level of immunity in all animals. Three months after
      the second vaccination, calves were either challenged with one of the mutant
      isolates or with a conventional challenge strain of BHV-1. Regardless of the type
      of virus used for challenge, vaccinated calves experienced significantly (P <
      0.05) less weight loss and temperature rises, had lower nasal scores, and shed
      less virus than non-vaccinated animals. The only statistically significant (P <
      0.05) difference between the 2 challenge viruses was the amount of virus shed,
      which was higher in non-vaccinated calves challenged with the mutant virus than
      in those challenged with the conventional virus. These data show that calves
      vaccinated with a modified-live IBR vaccine are protected from challenge with
      either the mutant or the conventional virus.

PMID- 11346261
TI  - Selection of an infectious bursal disease virus mutant with increased
      immunogenicity following passage under humoral immune pressure.
AB  - It is generally known that the pathogenicity of infectious bursal disease virus
      (IBDV) strains decreases following passage in cell culture. However, there is no
      information about the effect of passage under immune pressure on the phenotypic
      and molecular properties of IBDV. In the present study, a small plaque mutant
      virus with poor neutralization capability, but showing similar growth
      characteristics as the parental virus strain, QC2, was isolated after serial
      passage in Vero cells in presence of IBDV serotype 1 chicken polyclonal
      antiserum. This mutant virus showed reduced pathogenicity but enhanced
      immunogenicity compared to the parental virus. Sequence analysis of the non
      coding regions of the genome revealed 4 and 3 nucleotide changes in the 3' non
      coding regions of segments A and B, respectively, and none in the 5' non-coding
      regions. Restriction enzyme analysis of selected coding regions of the IBDV
      genome in both viruses revealed a loss of the PstI site in the VP2 region of the
      mutant virus. Selection of such mutant viruses by passaging under immune pressure
      may offer an improved method for developing safer and more effective attenuated
      vaccine strains against infectious bursal disease of chickens.

PMID- 11346263
TI  - Cryptococcus neoformans variety gattii.
AB  - Cryptococcus neoformans var. gattii is emerging as a primary human pathogen which
      is distinct genetically and biochemically from C. neoformans var. neoformans.
      There is increasing evidence that it should be reclassified as a separate species
      within the Tremellales. In nature, C. n. var. gattii has been consistently
      isolated from decaying wood in hollows of species of the red gum group of
      eucalyptus trees (Eucalyptus ser. Exsertae Blakely). The role that trees play in
      the life-cycle of C. n. var. gattii is not known, but its association with
      decaying wood is suggestive of an endophytic existence, in common with other wood
      rot fungi. Despite the demonstration in the laboratory of sexual reproduction
      between mating types oc and a of F. neoformans var. gattii, this has not been
      demonstrated in nature. Human cryptococcosis develops following environmental
      exposure and inhalation of the infectious propagule. Whether this is the
      basidiospore or dessicated yeast form is uncertain. The major risk factor for
      development of disease appears to be exposure, though there is indirect evidence
      that unidentified host factors may contribute to the relatively high incidence of
      cryptococcosis in Australian Aboriginals. The rarity of cryptococcosis due to C.
      n. var. gattii in immunocompromised patients remains unexplained. Virulence
      determinants of C. neoformans are currently the subject of intensive
      investigation, especially in C. n. var. neoformans. The best-characterized,
      major, virulence determinants in this variety, the polysaccharide capsule,
      products of the laccase enzyme pathway and ability to grow at physiological
      temperatures, contribute to its survival in the host. They are also present in C.
      n. var. gattii. A potential determinant of tissue invasion, secreted
      phospholipase B, is produced in vitro and in vivo by C. n. var. gattii. This
      enzyme has now been confirmed to play a role in the virulence of C. neoformans
      serotype A. Disease caused by C. n. var. gattii is distinguished from that due to
      C. n. var. neoformans by an increased incidence of cryptococcomas in lung and
      brain, increased neurological morbidity and a slower response to antifungal
      therapy. The difference in clinical presentation is predominantly due to the
      effect of underlying immunocompromise in patients infected with C. n. var.
      neoformans.

PMID- 11346262
TI  - Morphological and biochemical assessment of the liver response to excess dietary
      copper in Fischer 344 rats.
AB  - The aim of this study was to determine the amount of excess dietary copper (Cu)
      necessary to experimentally induce liver lesions characteristic of Cu-associated
      disease in Fischer 344 rats. Male weanling Fischer 344 rats of uniform age were
      divided into 6 groups (n = 5) and fed a rodent diet containing 18 (control), 750,
      1000, 1250, 1500, and 2000 microg/g Cu added as CuSO4. Rats were euthanized after
      3 months on the experimental diets and their livers processed for histology,
      histochemistry, Cu analysis (by atomic absorption spectrophotometry), and
      quantification of malondialdehyde (MDA) by the thiobarbituric acid reaction.
      Hepatic Cu levels were significantly higher (P < 0.01) in rats receiving over
      1000 microg/g Cu compared to the controls (means for each diet: control = 4.8
      microg/g, 750 microg/g Cu = 39.6 microg/g, 1000 microg/g Cu = 111.2 microg/g,
      1250 microg/g Cu = 389 microg/g, 1500 microg/g Cu = 509.4 microg/g, and 2000
      microg/g Cu = 766 microg/g). Histological lesions increased gradually according
      to the level of dietary Cu. Significant morphologic changes (necrosis, portal
      inflammation, hyaline remnants) and reduced growth rate occurred in rats
      receiving over 1250 microg/g Cu. However, no significant differences were found
      for MDA levels between groups. The present study demonstrates that compared to
      other species, very high levels of excess dietary Cu are needed to induce
      significant liver injury in Fischer 344 rats. Increased MDA content was not
      detected in rats with morphologic evidence of liver damage, suggesting that lipid
      peroxidation may not play a major role in this model of Cu toxicity.

PMID- 11346264
TI  - Human phagocytic cell responses to Scedosporium prolificans.
AB  - Scedosporium prolificans (SP) is an emerging opportunistic dematiaceous mould
      that causes serious infections in immunocompromised patients. Antifungal
      activities of human polymorphonuclear (PMN) and mononuclear (MNC) leukocytes
      against five SP isolates and Aspergillus fumigatus (AF) were evaluated. While
      monocyte-derived macrophages (MDM) phagocytosed conidia of both organisms
      comparably, they inhibited the germination of S. prolificans conidia less
      efficiently than those of A. fumigatus. Unopsonized hyphae of SP strains
      decreased the superoxide anion (O2-) produced by both PMN and MNC, whereas
      opsonized hyphae significantly stimulated it. In comparison to AF, phagocytes
      generally exhibited equal oxidative burst in response to SP. While PMN- and MNC
      induced hyphal damage was similar among SP strains, phagocytes tended to damage
      SP hyphae to an equal or higher degree than AF hyphae. The susceptibility of SP
      to phagocytes contrasts with its high resistance to antifungal agents and may be
      related with the very low pathogenicity of the mould.

PMID- 11346265
TI  - Tinea unguium in Lahore, Pakistan.
AB  - During a period of 1 year, out of 202 clinically suspected cases of tinea
      unguium, 53 (26%) were confirmed by mycological cultures for dermatophytes.
      Trichophyton rubrum was the most common fungus isolated in 46 (87%) patients,
      followed by T. violaceum in four (7%), T. interdigitale in two (4%) and
      Epidermophyton floccosum in one (2%). The disease was more common in adult males
      and fingernails were found to be affected more often than toenails. The distal
      and lateral variety was seen in 41 (77%) patients, total secondary dystrophic
      type in 11 (21%) and proximal subungual type in one (2%). Clinical diagnosis
      alone is not reliable and mycological confirmation is mandatory for this
      potentially curable disease.

PMID- 11346266
TI  - Etiology of dermatophytoses amongst children in northeastern Nigeria.
AB  - A survey of dermatophytoses was carried out amongst primary school children in
      Borno State, Nigeria, during February 1997 to January 1998. A total of 2,193
      children aged 4-16 years were screened. Out of these, 154 (7.0%) were proved to
      be mycologically positive by microscopy, culture or both. Incidence was
      significantly higher (P <0.05) in young children aged 7-11 years (8.1%) and 4-6
      years (6.9%) than in older children aged 12-16 years (3.6%). There was a
      significant difference in the incidence of dermatophytoses amongst children in
      urban and rural areas (P <0.05). Tinea capitis was the predominant clinical type
      followed by tinea corporis. Trichophyton schoenleinii was the most prevalent
      etiological agent (28.1%), followed by T. verrucosum (20.2%) and Microsporum
      gallinae (18.4%). Other species recovered included T. mentagrophytes (16.7%), T.
      tonsurans (10.5%), T. yaoundei (4.4%) and M. gypseum (1.8%).

PMID- 11346267
TI  - PCR fingerprinting: a convenient molecular tool to distinguish between Candida
      dubliniensis and Candida albicans.
AB  - Candida dubliniensis was recently identified as a germ-tube- and chlamydospore
      positive yeast, phenotypically and morphologically indistinguishable from the
      phylogenetically closely related yeast species C. albicans and its synonymized
      variant C. stellatoidea. The high similarity between these yeast species causes
      significant problems in the correct identification of C. dubliniensis in a
      standard clinical mycology laboratory. Polymerase chain reaction (PCR)
      fingerprinting was successfully applied here to distinguish between clinical
      isolates of the two closely related species. Microsatellite ([GACA]4) and
      minisatellite ([5'-GAGGGTGGCGGTTCT-3'], derived from the core-sequence of the
      wild-type phage M13) specific oligonucleotides were used as single primers in PCR
      to amplify hypervariable inter-repeat DNA sequences from 16 C. dubliniensis
      strains and 11 C. albicans strains. Each species, represented by its ex-type
      strain, could be identified by a distinct species-specific multilocus pattern,
      allowing identification to species level for all clinical isolates. In addition,
      the PCR fingerprinting generated strain-specific profiles, making this method
      applicable to epidemiological investigations. PCR fingerprinting using the primer
      M13 is proposed here as a simple, reliable and highly reproducible molecular tool
      to differentiate between strains of C. albicans and C. dubliniensis.

PMID- 11346268
TI  - Afut2, a new family of degenerate gypsy-like retrotransposon from Aspergillus
      fumigatus.
AB  - Four recombinant lambda clones containing non-ribosomal repetitive DNA sequences
      useful for fingerprinting Aspergillus fumigatus strains contained a new member of
      the gypsy family of retrotransposons, Afut2. It is 5810 bp in length with long
      terminal repeats of 245 bp and is defective. All non-ribosomal repetitive DNA
      sequences isolated so far in A. fumigatus are defective retrotransposons of the
      gypsy family.

PMID- 11346269
TI  - Epidemiology of Malassezia yeasts associated with pityriasis versicolor in
      Ontario, Canada.
AB  - The genus Malassezia was recently revised to include seven species, but the
      clinical significance of each of these species is not clearly understood. To
      obtain a better understanding of the contribution of individual Malassezia
      species to the epidemiology of pityriasis (tinea) versicolor, we used Leeming
      Notman medium to culture patient skin specimens showing positive evidence of
      Malassezia infection in direct microscopy. Isolates were identified on the basis
      of recently published morphological and physiological tests for distinction of
      the new species. Identification using recently developed molecular criteria was
      also carried out for the ambiguous cases. Malassezia species were cultured from
      111 cases of pityriasis versicolor in the Canadian province of Ontario. The most
      frequently isolated species were Malassezia sympodialis, M. globosa and M. furfur
      which respectively made up 59.4%, 25.2% and 10.8% of the isolated etiological
      agents. M. globosa was commonly isolated from a small number of pityriasis
      versicolor specimens obtained from investigators outside Canada. A large number
      of additional Ontario specimens with positive direct microscopy failed to yield a
      culture; however, it is suggested that this is consistent with the standard
      sampling practice of scraping the older portions of pityriasis lesions rather
      than the margins, where viable fungal cells are most likely to occur.

PMID- 11346270
TI  - DNA fingerprinting of serial Candida albicans isolates obtained during
      itraconazole prophylaxis in patients with AIDS.
AB  - During a randomized double-blind placebo-controlled study testing the efficacy of
      itraconazole for prophylaxis of systemic and mucosal fungal infections in
      patients with acquired immune deficiency syndrome, 298 patients were enrolled
      with 295 evaluable. Of those, 46 patients were considered prophylaxis failures
      because of recurrent oral or esophageal candidiasis. Oropharyngeal fungal
      cultures were taken at the time of suspected thrush or Candida esophagitis, but
      not at baseline. All of the Candida spp. isolates were cultured on CHROMagar
      Candida medium then identified using API 20 AUX strips. Antifungal susceptibility
      testing was performed following the National Committee for Clinical Laboratory
      Standards M-27A guidelines. Sequential isolates were genotyped using randomly
      amplified polymorphic DNA. Polymerase chain reaction fingerprints were generated
      using two repetitive sequence primers, (GGA)7 and (GACA)4. The study group
      consisted of 23 patients, nine from the itraconazole arm and 14 from the placebo
      arm, who were prophylaxis failures and had more than two C. albicans isolates.
      Five of 23 had isolates showing a > or =4-fold reduction in susceptibility; four
      of these patients were in the itraconazole prophylaxis arm and one was in the
      placebo arm. Three of the five had yeast isolations showing changes in banding
      patterns over time. Such changes may indicate genetic changes in the same strain
      that could be linked to acquired resistance to itraconazole, or acquisition of a
      new strain, or emergence of a previously minor component of the original
      population.

PMID- 11346271
TI  - A specific PCR assay for the dermatophyte fungus Microsporum canis.
AB  - A DNA fragment of approximately 1.2 kb, generated from the common dermatophyte
      Microsporum canis by arbitrarily primed polymerase chain reaction (PCR) using
      random primer OPU13, was cloned and sequenced. Based on the resulting sequencing
      data, a forward primer (MC1F) and a reverse primer (MC1R) have been designed and
      assessed by PCR for their usefulness in the improved identification of M. canis.
      The results obtained suggest that these primers are specific for M. canis, as a
      band of 900 bp was amplified in PCR with genomic DNA from M. canis only, and not
      from any of the other dermatophyte species or varieties, other fungi or common
      bacteria examined. Combining this PCR technique with a rapid mini-preparation
      method for fungal DNA, a definitive diagnosis of M. canis can be achieved within
      a day from the primary cultures. Future refinement of a DNA purification protocol
      from clinical specimens would further enhance the potential of the PCR based test
      for improved detection and identification of M. canis.

PMID- 11346272
TI  - Protective effect of Nocardia opaca lysozyme digest in experimental murine
      Candida albicans infections.
AB  - Candida albicans, as an opportunistic pathogen, causes therapeutic problems in
      immunocompetent individuals and frequently it initiates severe infections in
      immunocompromised hosts. The application of a lysozyme digest preparation from
      the cell walls of Nocardia opaca (Nocardia lysozyme digest; NLD), recently
      classified as Rhodococcus opacus, has a protective effect in intravenous (i.v.)
      C. albicans infections in inbred ICR mice which have normal complement
      production. It also significantly reduces i.v. and intraperitoneal (i.p.)
      infections in DBA/2 mice which are deficient in C5 complement component. A
      significant decrease in C. albicans recovery from kidneys was found in NLD
      treated DBA/2 animals. The preparation enhanced delayed type hypersensitivity to
      the yeast cells in both mouse strains. C. albicans-induced popliteal lymph node
      reactions were increased in ICR mice. In addition, mouse splenocytes that had
      been inhibited in their proliferative response to phytohaemagglutinin had this
      response restored after exposure to the preparation. NLD decreased the
      sensitivity of both mouse strains to a second challenge with the pathogen. The
      preparation restored the impaired host response to C. albicans infection in ICR
      mice treated with cobra venom and cyclophosphamide.

PMID- 11346273
TI  - A case of feline otitis externa due to Microsporum canis.
AB  - We describe a case of a 3-month-old Persian male cat with a persistent waxy,
      ceruminous, otic discharge in both external auditory canals. After
      microbiological culture, only Microsporum canis was isolated with no concurrent
      fungal or bacterial flora. Fungal otitis due to dermatophytes was diagnosed and
      specific treatment with griseofulvin was administered. After 4 weeks of
      treatment, no M. canis colonies were isolated and clinical recovery had occurred.
      In view of this case, dermatophytosis should be included in the differential
      diagnosis of feline otic conditions, particularly when otitis becomes chronic or
      is refractory to treatment.

PMID- 11346274
TI  - Diagnosis, self-help, and maintenance care as key constructs in treatment
      research for "alcohol use disorders" (AUD).
AB  - OBJECTIVE: This study examines a sample of alcohol user treatment outcome studies
      to determine the amount of attention given to three areas of concern and cost
      effectiveness in treatment research: patient diagnosis, use of self-help groups
      (e.g., Alcoholics Anonymous [AA]), and use of maintenance care services (also
      known as a "aftercare"). METHOD: A preliminary sample of 40 studies was coded for
      the degree of specific information provided to each of the three areas of
      interest. RESULTS: Eight studies in the sample did not mention the diagnostic
      criteria used to determine patient addiction, 18 did not mention use, referral,
      or recommendation of AA, and 20 did not mention use, referral, or recommendation
      of maintenance care services. CONCLUSIONS: As cost-effective additions to primary
      treatment, AA and maintenance care services deserve greater attention in the
      treatment of "substance abuse disorders." Researchers should also pay greater
      attention to patient diagnosis as an integral part of patient care. Finally,
      journal editors should institute minimum requirements for published reports
      ensuring that sufficient information on patient care is provided.

PMID- 11346275
TI  - The social ecology of the co-occurrence of substance use and early coitus among
      poor, urban black female adolescents.
AB  - Currently, the profession of social work has proclaimed the need for an empirical
      research agenda to broaden its knowledge base. The profession's positivists
      rightly argue that a sound knowledge base is derived from rigorous scientific
      empirical methods. Unquestionably, the profession's unique contribution to the
      study of human development has been its emphasis on environmental effects and
      individual adaptation. Presently, social scientists embrace an ecological
      perspective when studying how social environmental effects are mediated. As
      researchers shift to a social ecological perspective, an empirical contextual
      model will allow the study of racial/ethnic differences in the incidence of
      adolescent problem behaviors (Stevens, 1998). An examination of the social
      ecology of poor, urban black female adolescents was undertaken to examine claims
      of the co-occurrence of early coitus and substance use, behaviors evident in
      black adolescents. An ecological framework operationalized by the constructs
      structural strain, kinscriptions, and community bridging is used to explicate how
      coital behavior among black females may not co-occur with drug use. The article's
      exegesis is directed by four postulates that help clarify the relationship of
      social ecology to the linkage of early coital behavior and substance use. The
      article concludes with adolescent narratives that illumine the cogency of the
      ecological analysis.

PMID- 11346276
TI  - Smokeless tobacco use among adults in the Northern Province of South Africa:
      qualitative data from focus groups.
AB  - The aim of this study was to investigate perceptions on the use of smokeless
      tobacco in the Northern Province, South Africa. Ten focus groups were conducted
      in 1999 with two heterogeneous groups (5 with middle-aged and 5 with the aged).
      They were mainly Northern Sotho speaking. From 72 participants 16 women and 8 men
      admitted to using snuff. The most popular types of smokeless tobacco used were
      homemade snuff and only a few used "commercial" snuff. The basic ingredients for
      homemade snuff were tobacco and other plant leaves. Snuff was found to have
      important functions and to be socially acceptable in the groups studied mainly
      for ceremonial and medicinal use and to a lesser degree for relaxation and
      pleasure. Generally, positive and medicinal effects were noted for snuff use.
      Most participants agreed that it is addictive, but only a few acknowledged the
      negative effects in terms of causing cancer.

PMID- 11346277
TI  - Sociodemographic correlates of abstinence and excessive drinking in the Greek
      population.
AB  - The objective of this study was to investigate the determinants of abstinence and
      drinking patterns among 14,367 Greeks. Participants older than 60, single and
      widowed men, as well as participants living outside the Greater Athens area were
      significantly more likely to abstain than to be "light to moderate" drinkers. In
      contrast, those at higher educational levels and those separated or divorced were
      less likely to abstain than their counterparts. With respect to excessive
      drinking, older people and those at higher educational levels were less likely to
      engage excessive drinking than their counterparts. Among men, subjects who were
      separated or divorced were more likely to drink excessively than those who were
      married. The results of our study help detect groups at high risk for diseases
      associated with high or low consumption of alcohol, and outline preventive
      strategies.

PMID- 11346278
TI  - Linguistic acculturation associated with higher marijuana and polydrug use among
      Hispanic adolescents.
AB  - Hispanic sixth and seventh graders in 22 New York City middle schools (mean age:
      12.66 years) completed self-report questionnaires with items related to drug use
      (cigarette smoking, alcohol use, and marijuana) use and linguistic acculturation
      at two assessments (N = 1299 at baseline; N = 1038 at 1-year follow-up).
      Adolescents who spoke English with their parents smoked marijuana more frequently
      than those who spoke Spanish with their parents at both surveys. By the 1-year
      follow-up, students who spoke English with their parents and bilingual students
      who spoke English and Spanish with their parents engaged in greater polydrug use
      than those who spoke Spanish with their parents.

PMID- 11346279
TI  - Using social indicators to estimate county-level substance use intervention and
      treatment needs.
AB  - This study describes the development of a model for estimating county-level
      substance use intervention and treatment needs using social indicators. Forty
      five indicators conceptually related to substance misuse were reduced through
      factor analysis. Logistic regression models were then developed using selected
      indicators to predict service needs. The following variables were significant
      predictors of substance use intervention and treatment needs: the percent of the
      population who is male aged 15 to 34, urbanicity, and population density. The
      results suggest that substance misuse may be successfully modeled by a few easy
      to obtain and reliably measured variables describing the population
      characteristics of local communities.

PMID- 11346280
TI  - Hepatitis C among noninjecting drug users: a report.
AB  - OBJECTIVES: This report documents the prevalence of hepatitis C virus (HCV)
      infection among self-reported noninjecting drug users recruited from two New York
      City neighborhoods. METHODS: Participants were recruited in separate studies from
      East Harlem and the Lower East Side of Manhattan and were administered structured
      questionnaires and tested for HCV. RESULTS: HCV prevalence rates among those
      reporting no history of injecting drugs ranged from 5% to 29%, according to age,
      gender, and study location. CONCLUSIONS: Our results suggest that more research
      is needed to elucidate potential noninjecting routes of HCV transmission among
      drug users. Moreover, policies that rely predominantly on injector status as the
      only drug-related risk factor for HCV screening need to be reassessed in light of
      these findings.

PMID- 11346281
TI  - An investigation of the adsorption of organic dyes onto organo-montmorillonite.
AB  - Adsorption of organic dyes, crystal violet (CV), orange II (OR), and phenol red
      (PR), onto organo-clay was investigated in a batch type reactor at 25 degrees C.
      The organo-clay was obtained by modifying montmorillonite with a cationic
      surfactant, cetylpyridinium (CP), and used as an adsorbent. We conducted
      experiments to find out the effect of pH and solvent on the adsorption affinity
      of organic dyes for the modified montmorillonite. From the results, we observed
      that the adsorption capacity on the organo-montmorillonite decreased in the order
      CV > OR > PR at all pH values examined (pH 3, pH 7, and pH 11). It mostly
      resulted from the difference in solubility and the molecular weight of the
      solutes. In a 30-V/V % methanol/water cosolvent solution, the adsorption capacity
      of the dyes decreased compared to that in aqueous solution. In addition, the
      adsorption capacities of OR and PR on CV-montmorillonite were lower than those on
      CP-montmorillonite. These results might show that partitioning by CP was superior
      to the adsorption by CV to hold the solute molecules on the surface of
      montmorillonite. The Langmuir and Redlich-Peterson (RP) models were used to
      represent the adsorption equilibria of the organic dyes.

PMID- 11346282
TI  - Seasonal variations in the microbial population density present in biological
      sludge.
AB  - Sludge produced during the treatment of wastewater is being used as fertilizer in
      several Gulf countries. The Water and Sewage Authority of Saudi Arabia has
      targeted the reuse of the total amount of sludge in the future. However, these
      sludges should be properly treated before reuse as they contain a large number of
      pathogens and parasites. Little information is available on the microbial
      characteristics of sludge produced in wastewater treatment plants operating in
      this region. Variations in the population densities measured by Standard Plate
      Count, total coliform, fecal coliform, coliphage, and Clostridium perfringens
      present in the sludge, were monitored during a one year study at Al-Khobar
      wastewater treatment plant so that the effect of seasonal variations on the fate
      of these five indicator microorganisms could be investigated. This paper covers
      an evaluation of the fate of indicator microorganisms in the drying sludge.
      Insight gained in this study will be helpful in establishing guidelines for the
      use of sludge as fertilizer for agriculture purposes.

PMID- 11346283
TI  - Anaerobic sulphate-reducing microbial process using UASB reactor for heavy metals
      decontamination.
AB  - This study was conducted to investigate the possibility of using sewage as an
      organic substrate for the growth of sulphate reducing bacteria (SRB) and to
      acclimatise anaerobic sludge to produce sulphide from sulphate reduction, with a
      view to metal precipitation. The experiments were carried out in a continuous
      bench-scale bioreactor (13 1 UASB reactor) operated with hydraulic retention
      times (HRT) of 11 and 19 hours. The feed solution used was composed of the liquid
      part of the sewage (organic matter) supplemented with nickel sulphate and sodium
      sulphate. The results showed that it was possible to acclimatise anaerobic sludge
      for production of sulphide by sulphate reduction. A relation between the
      available COD and the concentration of sulphate reduced by SRB was observed. High
      nickel removal efficiency (96%) was obtained during the whole operation (320
      days). However, the process required very strict control of the organic load
      available (sewage) in the solution and, if necessary, the addition of a
      complementary organic carbon source, in order to maintain a constant level of
      metal removal. The SRB were not affected by the HRT values studied and were
      installed and maintained in the system; however, granular sludge was not
      observed. The micrographs confirmed the presence of iron and nickel sulphides and
      also a mixed bacterial culture in the anaerobic sludge. The EDS spectrum of the
      sludge showed that nickel was retained in the sludge predominantly as a nickel
      sulphide.

PMID- 11346284
TI  - Multi-step sequential batch two-phase anaerobic composting of food waste.
AB  - This study was conducted to evaluate the newly devised process, called MUlti-step
      Sequential batch Two-phase Anaerobic Composting (MUSTAC). The MUSTAC process
      consisted of several leaching beds for hydrolysis, acidification and post
      treatment, and a UASB reactor for methane recovery. This process to treat food
      waste was developed with a high-rate anaerobic composting technique based on the
      rate-limiting step approach. Rumen microorganisms were inoculated to improve the
      low efficiency of acidogenic fermentation. Both two-phase anaerobic digestion and
      sequential batch operation were used to control environmental constraints in
      anaerobic degradation. The MUSTAC process demonstrated excellent performance as
      it resulted in a large reduction in volatile solids (VS) (84.7%) and high methane
      conversion efficiency (84.4%) at high organic loading rates (10.8 kg VS m(-3) d(
      1)) in a short SRT (10 days). Methane yield was 0.27 m3 kg(-1) VS, while methane
      gas production rate was 2.27 m3 m(-3) d(-1). The output from the post-treatment
      could be used as a soil amendment, which was produced at the same acidogenic
      fermenter without troublesome moving. The main advantages of the MUSTAC process
      were simple operation and high efficiency. The MUSTAC process proved stable,
      reliable and effective in resource recovery as well as waste stabilization.

PMID- 11346285
TI  - Prediction of a membrane-coupled anaerobic VFA fermenter efficiency using an
      empirical model.
AB  - An empirical model based on some statistical analysis for predicting produced
      volatile fatty acids (VFA) concentration was developed to establish reliable
      design conditions of a membrane-coupled anaerobic VFA fermenter (MCAVF) and
      assess its performance with influent organics concentration (Ci), membrane
      filtration ratio (phi) and hydraulic loading rate (HLR). The empirical model
      followed the same trend as the experimental data, which showed the effectiveness
      of the model. The relationship involving these three independent variables
      explained more than 90% of the variation in the dependent variable. A model
      explains that the produced VFA concentration is more sensitive to changes in
      influent organics concentration (Ci) and membrane filtration ratio (phi) than
      hydraulic loading rate (HLR). This empirical model can predict the optimum values
      of operation parameters on many scenarios. Due to its simplicity, the empirical
      model can be used to design and operate a membrane-coupled anaerobic VFAs
      fermenter.

PMID- 11346286
TI  - A pre- and post-denitrification system treating a very high ammonia landfill
      leachate: effects of pH change on process performance.
AB  - The prime objective of this research was to investigate the nitrogen removal
      capabilities of a pre- and post-denitrification process, when treating landfill
      leachate containing an ammonia concentration of over 2,200 mg N l(-1). The
      treatment system, also known as a 4-Stage Bardenpho process, was operated with an
      external recycle ratio of 3:1 and an internal recycle ratio of 4:1. The first
      anoxic reactor actual hydraulic retention time was 1.5 hours, while the first
      aerobic retention time was 3 hours. The very high ammonia concentration was
      simulated by pumping ammonium chloride into the first anoxic reactor of the
      system. Methanol was used as the organic carbon source for denitrification. At an
      influent ammonia concentration of about 2,200 mg N l(-1), the anoxic pH levels
      stabilized at about 8.6 within the first reactor, and at about 9.8 within the
      second reactor. These high anoxic pH levels were partially responsible for
      decreased denitrification and, hence, residual NO concentrations in the effluent.
      By decreasing the pH in the anoxic basins, the overall performance of the system
      immediately improved; the effluent NOx concentration decreased rapidly over a
      period of about six days, from an average 80 mg N l(-1) to about 60 mg N l(-1),
      with some samples as low as 40 mg N l(-1). Subsequently, increased leachate
      toxicity resulted in an unexpected system failure; although the treatment system
      eventually recovered and stabilized, denitrification in each anoxic reactor
      remained at only about 55%, with final effluent NOx concentrations of over 100 mg
      N l(-1). Despite this reduced level of performance, the decrease in anoxic pH
      resulted in enhanced nitrification performance, complete ammonia removal in the
      first aerobic reactor, and a more stable, overall performance in the 4-Stage
      Bardenpho process.

PMID- 11346287
TI  - The phytotoxicity to tobacco plants of short-chain carboxylic acids at
      atmospheric concentration levels in urban areas.
AB  - In this paper, we describe the influence of monocarboxylic acids (formic acid and
      acetic acid) and dicarboxylic acids (succinic acid and adipic acid), which are
      usually contained in aerosol particles and fog water, on the growth of tobacco
      plant. Their influence was examined by spraying the acid solutions on intact
      plants and by administering them in a culture medium for suspension-cultured
      cells. Their growth rates suggest that the influence of short-chain
      monocarboxylic acids was not significant in both the intact plant experiment and
      the cell culture experiment. In contrast, dicarboxylic acids exhibited
      significant influence on the growth of intact plants and no influence on culture
      cells, indicating that their toxicity is exerted mainly on the tissue of leaf
      surface. Phytotoxicity of dicarboxylic acids is higher than that of
      monocarboxylic acids.

PMID- 11346288
TI  - Heavy metal pollution of road dust and roadside soil near a major rural highway.
AB  - The concentrations of lead, copper, cadmium, zinc, nickel and chromium were
      measured in road dust and roadside soils from a French major highway. The
      profiles of total levels in the soil as a function of distance from the road edge
      and as a function of depth were investigated. Lead, zinc, copper and, to a lesser
      extent, cadmium contamination were found in samples taken on the surface and in
      the immediate vicinity of the road. The observed concentrations decreased rapidly
      with distance and depth. Soil samples appeared to exhibit little nickel and
      chromium pollution. The geochemical phases on which heavy metals (lead, copper,
      zinc, cadmium and chromium) were fixed preferentially, as well as the potential
      mobility of the different metals under certain physical and chemical conditions
      were evaluated. Sequential extractions and single extractions with different
      reagents were performed. Chromium, which was present mostly in residual form, was
      mainly of natural origin in the studied samples and was not highly mobilisable.
      Cadmium was the most easily exchangeable element in case of variations in the
      physical and chemical conditions but the quantities involved remained small. Lead
      and copper did not appear to be highly mobile. Only drastic conditions, such as
      those that may be produced by accidental spillage of a chemical product (acid or
      complexing agent), mobilised them quantitatively. A significant risk of
      mobilisation was to be feared only in the case of zinc, which is very sensitive
      to acid pH.

PMID- 11346289
TI  - Organic and hydraulic shock loadings on a biological aerated filter.
AB  - The performance of a biological aerated filter (BAF) during short-term (60 min)
      organic and hydraulic shock loads was investigated. The BAF used for the present
      experiment was not capable of absorbing high peak organic shock loads when the
      organic loads were increased from a normal load of 1.2-1.4 kg soluble chemical
      oxygen demand (sCOD ) m(-3) d(-1) to shock loads between 5.1- 7.3 kg sCOD m(-3)
      d(-1), based on empty bed volumes. Nevertheless, the effect on the biomass was
      limited as normal performance resumed very quickly. Increases in the hydraulic
      velocity from 0.7-1.0 m h(-1) to 1.5-2.9 m h(-1) had little effect on BAF
      performance in terms of soluble COD removal. Yet, sCOD effluent concentrations of
      <55 mg l(-1) (approximately 22 mg l(-1) biochemical oxygen demand) were always
      achieved. The recovery of the reactor in both cases was fast, resuming normal
      performance within 60 min after the application of the shock load.

PMID- 11346290
TI  - A pilot-scale study of tertiary treatment of Jizhuangzi wastewater treatment
      plant by continuous preozonation-microflocculation-filtration process.
AB  - A pilot-scale study of tertiary wastewater treatment of the JIZHUANGZI Municipal
      Wastewater Treatment Plant was carried out by preozonation, coagulation and
      direct filtration process with the aim of producing wastewater suitable for
      reuse. The proposed treatment scheme could produce a filtered water with lower
      turbidity, COD(Cr) and colour at lower ozone and coagulant dosages. Ozone was
      added into the mixing tank with coagulant simultaneously and postozonation was
      not cost effective. With the increase of ozone dosage, better COD(Cr) and colour
      removals were observed especially at the ozone dosage between 0.7-1.0 mg l(-1).
      Similarly, increasing ferric sulphate dosage resulted in better removals of
      turbidity, COD(Cr) and colour in the filtered water. In contrast, increasing
      polymer T-80 dosage seemed to improve colour removal rather than turbidity and
      COD(Cr). To achieve removal efficiency of 70% for turbidity, 45% for COD(Cr) and
      over 60% for colour, the optimum dosages of ozone, ferric sulphate and polymer T
      80 should be 0.7-1.0 mg l(-1), 10.0-12.5 mg l(-1) and 0.7-1.0 mg l(-1),
      respectively.

PMID- 11346291
TI  - Quantitative bioregeneration of granular activated carbon loaded with phenol and
      2,4-dichlorophenol.
AB  - Lignite based granular activated carbon of 20x30 mesh size was used to
      investigate the extent of bioregeneration of phenol and 2,4-DCP in a batch
      system. The adsorption isotherm fits very well with the Freundlich isotherm and
      it is apparent that 2,4-DCP is more adsorbable than phenol. The degree of
      reversible adsorption for phenol and 2,4-DCP were 32.9 and 10.6 %, respectively.
      The low percentages of their reversibility meant that the adsorption phenomena of
      both phenol and 2,4-DCP were not fully physicosorption. The microorganisms can
      regenerate 31.4% (21.2 mg g(-1)) of GAC loaded with phenol and 14.3% (24.8 mg g(
      1)) of GAC loaded with 2,4-DCP over a period of 7-10 days. The bioregeneration of
      phenols closely followed the first order kinetics with the rate constant of 0.046
      day(-1) at initial phenol concentration of 100 mg l(-1) and biomass concentration
      of 20 mg l(-1) MLVSS. The rate constant was 0.021 day(-1) at initial 2,4-DCP
      concentration of 200 mg l(-1) and 200 mg l(-1) MLVSS. In addition, the increasing
      in initial concentration of biomass in the solution shortened the time required
      to reach the asymptotic limit on the bioregeneration but rendered little impact
      on the bioregeneration percentage.

PMID- 11346292
TI  - Effect of copper sulfate addition on nitrous-oxide emission in high speed
      dentrification process using macro-porous cellulose carrier.
AB  - Nitrous oxide emission from the immobilized denitrification process was
      investigated under copper-added and copper-free conditions to realize high-speed
      denitrification with minimum nitrous oxide emission. Nitrous oxide emission was
      found to be smaller in culture using immobilized cells acclimatized under copper
      added condition. Transient phenomena of nitrous oxide emission, nitrate reduction
      and nitrite accumulation were then investigated in repeated batch experiments by
      transferring immobilized cells acclimatized in copper-free conditions into copper
      added medium. Nitrous oxide emission obviously decreased, and maximum nitrous
      oxide concentration of seventh batch culture was about 1/40,000 of that of first
      batch culture. Nitrate reduction gradually decreased from second batch to fourth
      batch culture and it turned to increase from fifth batch culture to seventh batch
      culture. At seventh batch culture, nitrate reduction rate was restored up to 80%
      of the initial speed. This repeated batch experiment clarified that nitrous oxide
      emission was repressed by copper sulfate addition. The effect of pH and
      temperature on nitrous oxide emission were also investigated in a continuous
      denitrification experiment under copper added conditions. Nitrous oxide emission
      was increased by lowering pH and lowering temperature. At optimum operating
      condition (pH8.0, 30 degrees C), nitrogen removal efficiency of 99.9%, nitrous
      oxide concentration in the emitted gas of 3.1ppm(v/v) and conversion ratio to
      nitrous oxide of 0.000316% were obtained when 280mg-Nl(-1) nitrate containing
      medium was treated at 6 hours of hydraulic retention time.

PMID- 11346293
TI  - Adsorption of ferrous iron on the lepidocrocite surface.
AB  - This study explored the ferrous iron adsorption capacity of three synthesized
      lepidocrocites as well as their morphology and surface area. Their morphologies
      were observed using scanning electron microscopy (SEM) and their surface areas
      were measured by BET isotherm techniques using nitrogen gas at the liquid
      nitrogen temperature. The adsorption capacities of the three distinctive
      lepidocrocites were measured and the data were processed by multiple regression
      technique to obtain the adsorption constants in the proposed model. The
      microphotographs of the lepidocrocites revealed that lepidocrocites could have an
      acicular shape as well as the shape of agglomerated flocs. The surface areas of
      the synthesized lepidocrocites in this study varied widely from 48.98 m2 g(-1) to
      150.28 m2 g(-1). Adsorption capacities of three distinctive lepidocrocites for
      ferrous iron were investigated at four different pH levels. It was observed that
      there was no correlation between the BET surface area and adsorption capacity.
      The sites accessible to nitrogen gas might not be available to ferrous iron in
      water. An adsorption model based on the Freundlich equation was built to predict
      the effect of pH and the equilibrium concentration of ferrous iron in water.
      Multiple regression of data revealed that the amount of ferrous iron adsorbed on
      the unit weight of lepidocrocite was proportional to the 0.57 power of the
      ferrous iron concentration and inversely proportional to the 0.66 power of the
      hydrogen ion concentration.

PMID- 11346294
TI  - Morphological and biochemical variations of Haemophilus influenzae type b induced
      by pH and temperature changes.
AB  - Haemophilus influenzae type b ATCC 10211 was cultured at different temperatures
      (25 degrees C-49 degrees C) and pH values (5.7-8.7) either in liquid or semisolid
      medium. Morphological variations of individual cells were noted by optical
      microscopy depending upon the conditions of growth. At higher temperatures
      filaments were produced whereby the length of individual cells increased compared
      to cultures grown at 37 degrees C. Filaments were also observed at lower pH
      values. Culture conditions also affected colonial morphology. At low pH values
      colonies had an enhanced lobulated contour and were more wrinkly and rougher than
      at higher pH. The changes in cellular and colonial morphology were correlated
      with distinct outer membrane protein profiles. The changes in temperature and pH
      did not affect identification of the microorganism by the API system.

PMID- 11346295
TI  - Weakly beta-haemolytic human intestinal spirochaetes antagonize the haemolytic
      activity of Clostridium perfringens alpha-toxin producer.
AB  - The production of haemolytic antagonism between weakly beta-haemolytic human
      intestinal spirochaetes (wbetaHIS) related to human intestinal spirochaetosis and
      Clostridium perfringens alpha-toxin producer was investigated. A reduction of the
      clostridial haemolytic activity and a distortion of the haemolytic halo of
      clostridial alpha-toxin surrounded by a small zone of poorly cooperative
      haemolysis was clearly observed on the level of the spirochaetal growth area when
      40 out of 41 wbetaHIS were cultivated in sheep blood agar plates together with
      Clostridium perfringens alpha-toxin producer. This phenomenon of haemolytic
      antagonism was observed only when wbetaHIS grew 72-96 hours sooner than C.
      perfringens and after the inoculum of the latter at a distance of 0 to 10 mm from
      wbetaHIS the plates were anaerobically incubated for an additional 48 hours and
      the bacteria were used at concentrations ranging from 10(7) to 10(4) CFU/ml.
      These results were also observed between C. perfringens and weakly beta
      haemolytic intestinal spirochaetes related to animal intestinal spirochaetosis
      including avian strains and Brachyspira (Serpulina) pilosicoli of porcine origin.

PMID- 11346296
TI  - Antimicrobial activity in urine: effect on leukocyte count and bacterial culture
      results.
AB  - A total of 500 urine specimens collected from non-hospitalized patients were
      investigated for leukocyte count by microscopy, bacterial recovery by culture,
      and detection of antimicrobial activity by disc diffusion. Results indicated that
      21% of the specimens contained leukocytes > or = 50/cu mm, whereas 14.4% of
      specimens revealed significant bacterial growth. The use of Staphylococcus aureus
      ATCC 29737 as a test bacterium detected the antimicrobial activity in 19.2% of
      the urine specimens, while the use of two clinical isolates of Escherichia coli
      detected this activity in fewer specimens. Evidence is provided which indicates
      that bacterial growth inhibitors in urine are mainly due to the intake of
      antibiotics by patients. These inhibitors confused the interpretation of urine
      culture results as they were found to play a major role in the occurrence of
      sterile pyorrhea and in reducing the number of specimens yielding significant
      bacterial growth.

PMID- 11346297
TI  - Nasal carriage of methicillin-resistant Staphylococcus aureus among smokers and
      cigarette factory workers.
AB  - Effects of smoking and tobacco on nasal carriage and colonisation rates of
      Staphylococcus aureus were investigated on 368 healthy males aged between 30 and
      40 years old. The study group comprised 100 non-smokers (control group), 91
      smokers, and 177 cigarette factory workers (42 smokers, 135 non-smokers).
      Quantitative cultures were done from the nasal swabs of all participants. After
      identification and determination of colony counts, S. aureus strains were tested
      for methicillin resistance using the oxacillin disk diffusion method. The rates
      of nasal carriage of S. aureus were found to be 30% in the control group, 33% in
      smokers, and 41% in cigarette factory workers. Overall, S. aureus colonisation (>
      or = 500 cfu/ml) was detected in 72% of the carriers (55/76). Colonisation rates
      were 43%, 63%, and 85% in the carriers of the study groups, respectively. An
      increasing colonisation rate was detected in accordance with the increasing
      number of cigarettes smoked per day, and smoking period. While methicillin
      resistant Staphylococcus aureus was only found in 3% of the 30 S. aureus strains
      isolated from the control group, its isolation rate was 20% in the 30 S. aureus
      isolates of the smokers, and 33% in the 72 S. aureus isolates of the cigarette
      factory workers. These results indicate that cigarette and/or tobacco appear to
      have noticeable effects on the ecology of the nose.

PMID- 11346298
TI  - Typing of Neisseria meningitidis isolates from patients with invasive disease by
      molecular analysis of porin genes.
AB  - Polymerase Chain Reaction-Restriction Fragment Length Polymorphism assay (PCR
      RFLP) for porA and porB genes of Neisseria meningitidis was applied to type 64
      strains isolated from cases of invasive disease in Italy. The technique was also
      successfully used on non-viable strains and on cerebrospinal fluid samples from
      patients with meningococcal meningitis diagnosed by PCR. RFLP patterns were
      obtained for all strains, including those nontypeable or nonsubtypeable by the
      serological methods. The results confirmed the usefulness of the PCR-RFLP for
      porA and porB genes of Neisseria meningitidis in differentiating strains
      belonging to the same serological type and provided discriminative patterns in
      the increased proportion of non serotypeable/serosubtypeable strains circulating
      in Italy in recent years.

PMID- 11346299
TI  - AP-PCR typing of Pseudomonas aeruginosa isolated from patients with cystic
      fibrosis.
AB  - Arbitrarily Primed Polymerase Chain Reaction has been used for an epidemiological
      evaluation of 42 strains of P. aeruginosa isolated from nine cystic fibrosis
      patients during a three-year investigation period. The resistance patterns of the
      same strains have also been evaluated. The AP-PCR type fingerprinting was
      perfomed with primers 10514 and 208. Resistance was evaluated by the Minimal
      Inhibitory Concentration method. With 10514 eleven different genotypes could be
      evidenced, while with 208 only five of them could be detected. During the
      investigation period patients were always colonised by the same genotype. A
      possible correlation between resistance pattern and genotype with both primers
      has shown, within the same patient, a correspondence of about 20% for 10514 and a
      correspondence of only 10% for 208. Patients are colonised by one or two strains
      of P. aeruginosa and there is no relation between genotype and resistance
      pattern.

PMID- 11346300
TI  - Risk factors for acquiring Helicobacter pylori infection in a group of Tuscan
      teenagers.
AB  - Risk factors for acquiring Helicobacter pylori infection include hygienic,
      social, and environmental conditions. Some of these conditions usually change
      over time. We therefore investigated the existence of risk factors in a group of
      teenagers living in a place with the same environmental characteristics, in which
      hygienic and crowding conditions have not changed significantly in the last 20
      years. A group of 164 students, mostly borne in 1977, attending four different
      schools, were examined serologically for H. pylori infection and CagA status. The
      importance of the risk factors for the transmission of the infection were
      evaluated by the chi2 test. P values <0.05 were considered significant. Twenty
      two students (13.4%) were H. pylori seropositive. Students attending teachers'
      college and high school of arts were infected significantly more often than those
      attending high school (P = 0.011 and P = 0.012, respectively). Students who
      smoked and students whose parents had a manual job had an increased risk of
      acquiring the infection (P = 0.002, and P = 0.036, respectively). Crowding
      conditions and the presence of domestic animals were close to being statistically
      significant. Other factors, such as gender, number of bathrooms and bedrooms,
      sharing the bed with adults as a child, presence of a sexual partner, and a
      family history of peptic ulcer and gastric cancer, did not increase the risk of
      infection. The prevalence of seropositivity for CagA was similar in the various
      risk groups. Manual job of parents and smoking were the most important factors
      for acquiring H. pylori infection.

PMID- 11346301
TI  - Evaluation of PCR methods for 5S-rDNA and p30 genes to detect Toxoplasma gondii
      in blood and other clinical samples.
AB  - During the last few years the direct diagnosis of Toxoplasma gondii infection has
      taken advantage of PCR. The present work tested the sensitivity and specificity
      of PCR for rDNA and p30 genes. Using ascitic fluid from infected mice rDNA PCR
      detected 0.5 tachyzoite/ml, while nested p30 PCR 1 tachyzoite/ml. The rDNA
      amplification was positive in all clinical samples from a single immuno
      compromised patient (blood, urine and bronchoalveolar fluid). In the same patient
      nested p30 PCR was positive only in urine and bronchoalveolar lavage (BAL) fluid.
      The rDNA and p30 amplicons were never found in any amniotic fluids tested. These
      results could prove the usefulness of rDNA amplification to detect T. gondii in
      blood.

PMID- 11346302
TI  - Variability of the N-protein and the intergenic region of the S RNA of tomato
      spotted wilt tospovirus (TSWV).
AB  - The genetic heterogeneity of the N protein gene and the intergenic region (IGR)
      of the S RNA from tomato spotted wilt virus (TSWV) isolates, collected in
      Bulgaria, were compared with isolates from other parts of the world. The results
      substantiated the highly conserved nature of the N protein. Twenty six
      independent sequences revealed only seven variable amino acid positions, common
      to all isolates. The type of amino acids present in these positions seems to be
      independent of the geographical origin. In contrast to the structural N protein,
      comparisons of the related IGR-sequences led to clusters correlated with the
      geographical origin of the isolates. Although the overall sequence homology in
      the IGRs was much lower than for the N proteins, three conserved parts within
      this region were identified. The outstanding part was a central area of 31
      nucleotides with a significantly increased GC-content. This was located in both
      viral- and viral-complement RNA at structures with similar foldings, which led to
      the assumption that this stabilised structure, rather than a sequence motive,
      might serve as a transcription terminator during the synthesis of the two mRNAs
      from the ambisense segments.

PMID- 11346303
TI  - Isolation and identification of Mycobacterium neoaurum from a patient with
      urinary infection.
AB  - Mycobacterium neoaurum is a novel species of Mycobacteria, until now only
      isolated from catheters in immunosuppressed patients. This report describes the
      isolation and identification of M. neoaurum from urine obtained from a
      hospitalized patient.

PMID- 11346304
TI  - Sensitivity of Borrelia and Leptospira to Quinupristin-dalfopristin (Synercid) in
      vitro.
AB  - In vitro activity of Quinupristin-dalfopristin (Synercid) against seventeen
      isolates of Borrelia burgdorferi and two representatives of Leptospira spp. was
      investigated. MICs ranged from 0.03 to 0.125 for B. burgdorferi and 0.125-0.25
      microg/ml for Leptospires. Time killing studies carried out with 2 MIC
      demonstrated U 3 log(10)-unit killing after 72 h, showing a significant activity
      against spirochetes, though at a lower level than other antibiotics in use in the
      therapy of Lyme disease and leptospirosis.

PMID- 11346305
TI  - Antibody to HIV-1 Tat protein, a key molecule in HIV-1 pathogenesis. A brief
      review.
AB  - In the last few years, literature reports have unequivocally established that the
      86-101 aminoacid Tat protein, essential for an efficient viral replication, can
      be actively secreted by infected cells. The contribution of extracellular Tat to
      the progression of viral infection is underlined by the ability of neutralizing
      anti Tat antibody to reduce the viral load in vitro and possibly also in vivo.
      Considering that at least some of the effect of Tat protein seem to be the
      consequence of an autocrine loop and that anti Tat antibody is an efficient
      inhibitor of viral replication, it is reasonable to suppose that extracellular
      Tat play a functional role in HIV-1 infection and that HIV antibody may interfere
      with a possible Tat driven pathogenesis. This review explores the meaning of anti
      Tat antibody in vitro and in vivo and its importance to shed more light on viral
      pathogenesis and the recent development of Tat containing vaccine.

PMID- 11346306
TI  - Cellular biology of somatostatin receptors.
AB  - Somatostatin, and the recently discovered neuropeptide cortistatin, exert their
      physiological actions via a family of six G protein-coupled receptors (sst1,
      sst2A, sst2B, sst3, sst4, sst5). Following the cloning of somatostatin receptors
      significant advances have been made in our understanding of their molecular,
      pharmacological and signaling properties although much progress remains to be
      done to define their physiological role in vivo. In this review, the present
      knowledge regarding neuroanatomical localization, signal transduction pathways,
      desensitization and internalization properties of somatostatin receptors is
      summarized. Evidence that somatostatin receptors can form homo- and heterodimers
      and can physically interact with members of the SSTRIP/Shank/ProSAP1/CortBP1
      family is also discussed.

PMID- 11346307
TI  - The N-terminal domain of substance P is required for complete homologous
      desensitization but not phosphorylation of the rat neurokinin-1 receptor.
AB  - The agonist activity of substance P (SP) is a function of the C-terminal domain
      of the peptide. A C-terminal SP fragment (SP(6-11)) and analog (septide) and
      neurokinin A (NKA; a related tachykinin with a divergent N-terminal amino acid
      sequence) were found to be full neurokinin-1 receptor (NK-1R) agonists, but were
      not able to desensitize the receptor maximally as much as SP. Substance P caused
      95.6 +/- 0.9% maximal desensitization of the NK-1R whereas SP(6-11), septide, and
      NKA(only)caused 74 +/- 3.5, 50.6 +/- 8, and 71.5 +/- 4.4% maximal
      desensitization, respectively (mean +/- SEM; P < 0.001 vs SP). When a series of
      SP C-terminal fragment peptides were tested for their NK-1R desensitizing
      activity, it was found that SP(5-11)and SP(6-11)caused significantly less maximal
      NK-1R desensitization than SP. SP N-terminal fragment peptides had no effect on
      the ability of SP(6-11)to compete with(3)H-SP binding, generate an IP(3)response,
      or cause NK-1R desensitization when tested with or without SP(6-11). SP, SP(6
      11), septide, and NKA all maximally stimulated 8-9-fold increases in NK-1R
      phosphorylation. When attached to the C-terminal domain of SP responsible for NK
      1R binding and agonism, the N-terminus of SP is responsible for 25-50% of
      homologous desensitization and this may occur via a mechanism other than NK-1R
      phosphorylation.

PMID- 11346308
TI  - Differential roles of spinal neurokinin 1/2 receptors in development of
      persistent spontaneous nociception and hyperalgesia induced by subcutaneous bee
      venom injection in the conscious rat.
AB  - To evaluate the roles of spinal neurokinin receptors in the development of
      persistent nociception and hyperalgesia to thermal and mechanical stimuli induced
      by subcutaneous (s.c.) bee venom injection, effects of intrathecal (i.t.) pre- or
      post-treatment with a non-selective antagonist of (NK1/2) receptors, [D-Arg1,D
      Trp7,9,Leu11] substance P (spantide), and a selective NK3 receptor antagonist,
      (S)-(N)-(1-(3-(1-benzoyl-3-(3,4-dichlorophenyl) piperidin-3-yl)propyl)-4
      phenylpiperidin-4-yl)-N-methyl acetamide (SR142801) were assessed in conscious
      rat. Injection of bee venom s.c. into the plantar surface of one hind paw
      resulted in a pathological pain phenomenon characterized by a 1-2 h single phase
      of persistent spontaneous nociceptive behaviors (continuously flinching the
      injected paw) and a 72-96 h profound primary thermal and mechanical hyperalgesia
      in the injection site and a secondary thermal hyperalgesia in the non-injected
      hindpaw. Pre-treatment with spantide i.t. at 0.05 microg, 0.5 microg and 5 microg
      produced a dose-related suppression of the bee venom-induced flinching reflex
      during the whole time course and the inhibitory rate was 24 +/- 12.60% (35.38 +/-
      4.12 flinches/5 min, n=5), 48 +/- 6.75% (24.53 +/- 2.90 flinches/5 min, n=5) and
      60 +/- 7.69% (18.88 +/- 3.58 flinches/5 min, n=5) respectively when compared with
      the saline control group (46.80 +/- 2.60 flinches/5 min, n=5). Post-treatment of
      spantide i.t. at the highest dose (5 microg) used in the present study 5 min
      after bee venom injection also produced a 49% suppression of the flinching reflex
      in the control group [post-spantide vs saline: 19.42 +/- 3.15 (n=5) vs 38.42 +/-
      3.25 flinches/5 min (n=5)]. Moreover, i.t. pre-treatment with 5 microg spantide
      partially prevented the primary and secondary thermal hyperalgesia from
      occurring, while it did not show any influence on the development of primary
      mechanical hyperalgesia. Neither the established thermal nor mechanical
      hyperalgesia identified in the above sites was affected by i.t. post-treatment
      with the same dose of spantide 3 h after bee venom injection. Pre and post
      treatment of SR142801 did not produce any significant effect on the bee venom
      induced spontaneous pain and thermal and mechanical hyperalgesia. Our present
      result suggests that activation of spinal NK1/2 receptors is involved in both
      induction and maintenance of the persistent spontaneous nociception, while it is
      only involved in induction of the primary and secondary thermal, but not primary
      mechanical hyperalgesia induced by s.c. bee venom injection. The spinal NK3
      receptor seems not likely to be involved in the bee venom-induced behavioral
      response characterized by spontaneous pain and thermal and mechanical
      hyperalgesia.

PMID- 11346309
TI  - Normalization of circulating leptin levels by fasting improves the reproductive
      function in obese OLETF female rats.
AB  - In order to examine a possible detrimental effect of hyperleptinemia on the
      reproductive system, we examined whether a decrease in circulating leptin levels
      by fasting affects the estradiol/progesterone-induced luteinizing hormone (LH)
      and prolactin (PRL) surges in genetically obese OLETF (Otsuka-Long-Evans
      Tokushima-Fatty) rats. Experiments were performed on both normally fed and 3-day
      starved groups from ovariectomized OLETF rats and their controls LETO (Long-Evans
      Tokushima-Otsuka). Starved LETO rats, whose leptin levels were less than 0.5
      ng/ml, did not show a significant surge of either LH or PRL. Normally fed OLETF
      rats, whose leptin levels were 9.7 +/- 1.8 ng/ml, showed a significant but small
      surge for both LH and PRL. Interestingly, starved OLETF rats, whose leptin levels
      (4.1 +/- 0.7 ng/ml) were similar to those in normally fed LETO rats (3.3 +/- 0.4
      ng/ml), had significantly greater surges of both hormones than normally fed OLETF
      group. This study demonstrates for the first time that the normalization of
      circulating leptin levels in female OLETF rats augments the steroid-induced LH
      and PRL surges, and also suggests a deleterious effect of hyperleptinemia on the
      reproductive axis.

PMID- 11346310
TI  - The gamma(2)-MSH peptide mediates a central analgesic effect via a GABA-ergic
      mechanism that is independent from activation of melanocortin receptors.
AB  - Using the latency for tail-flick after thermal stimulation we have assessed the
      effects of alpha-, gamma(1)- and gamma(2)-MSH on nociceptive threshold in the
      mice. Intracisternal injections of gamma(2)-MSH induced a distinct analgesia,
      while gamma(1)-MSH in the same doses gave only a minor analgesia. Intracisternal
      alpha-MSH instead gave a short-term hyperalgesia. The effect of gamma(2)-MSH was
      not blocked by any of the MC(4)/MC(3)receptor antagonist HS014, naloxone or by
      the prior intracisternal administrations of gamma(1)-MSH. However, the gamma(2)
      MSH analgesic response was completely attenuated by treating animals with the
      GABA(A)antagonist bicuculline. The gamma(2)-MSH analgesic effect was moreover
      additive to the analgesia afforded by muscimol and ethanol, but not to that
      afforded by diazepam. In addition both gamma(1)- and gamma(2)-MSH induced
      moderate catalepsy, but could at the same time attenuate haloperidol induced
      catalepsia. We conclude that gamma(2)-MSH mediates a central analgesic effect via
      GABA-receptor dependent pathway that is distinct from melanocortic- and opioid
      receptors. Moreover, the mechanism for gamma(2)-MSH's analgesic effect appears to
      be distinct from that causing moderate catalepsia by gamma-MSH's.

PMID- 11346311
TI  - Immunohistochemical detection of calcitonin gene-related peptide receptor (CGRPR)
      1 in the endothelium of human coronary artery and bronchial blood vessels.
AB  - The potent vasodilatory peptide, calcitonin gene-related peptide (CGRP) is
      present in the innervation of vascular tissue. The actions of CGRP occur via a
      receptor, CGRP receptor(R)-1, which is also a target for the cardioprotective
      peptide adrenomedullin. The human version of the pharmacologically-defined CGRPR
      1 has been cloned but its distribution and cellular location is unknown. A rabbit
      antibody was generated to a synthetic peptide that corresponds to the C-terminus
      of human CGRPR-1 Immunochemical analysis of the human cell-line, SK-N-MC, which
      exhibits functional expression of the CGRPR-1 confirmed the antibody's
      specificity. The antiserum revealed specific staining in the endothelium of human
      coronary arteries. The vascular smooth muscle and ventricular myocardium were not
      immunoreactive. In bronchial blood vessels CGRPR-1-immunoreactivity was detected
      in the endothelium of the venules and not in the arterioles, which is
      particularly relevant for elucidating the putative role of CGRP in inflammation
      in this tissue.

PMID- 11346312
TI  - Comparative studies on the memory-enhancing actions of captopril and losartan in
      mice using inhibitory shock avoidance paradigm.
AB  - Renin angiotensin system (RAS) in the central nervous system participates in the
      processing of sensory information, learning and memory processes. Inhibitors of
      RAS, particularly angiotensin converting enzyme (ACE) inhibitors and angiotensin
      II (Ang II) receptor antagonists are reported to have potential nootropic effects
      in various learning and memory paradigms. The neurochemical basis underlying
      nootropic effect of ACE inhibitors are unclear due to wide range of substrate for
      this enzyme. In this study, we compared the effect of ACE inhibitor captopril and
      a selective AT(1)receptor antagonist losartan in a step-up shock avoidance
      (active avoidance) task. Captopril (5-10 mg/kg) but not losartan (5-10 mg/kg)
      improved learning in the second trial of the acquisition test. However, both
      these drugs were equally effective in enhancing retention of memory when
      administered prior to training. Retention enhancing effect of captopril and
      losartan were reversed by post-acquisition test administration of L-NAME (15
      mg/kg), dizocilpine (0.05 mg/kg) and scopolamine (0.1 mg/kg). On the basis of
      above observations, it is concluded that decrease in endogenous Ang II activity
      in the brain might result in improved cognitive performance by enhancing cGMP
      pathways. However facilitation of acquisition only by captopril may be due to
      other putative mechanisms.

PMID- 11346313
TI  - Symptoms research: a fertile field.

PMID- 11346314
TI  - When do symptoms become a disease?
AB  - When do symptoms become a disease? Are there rules or norms, currently or in the
      past, that tell us when a particular collection of largely symptom-based criteria
      has enough specificity, utility, or plausibility to justify the appellation
      disease ? The history of numerous symptom-based diagnoses in use today suggests
      partial answers to these questions. The 19th-century shift to understanding ill
      health as a result of specific diseases, increasingly defined more by signs than
      symptoms, led to a loss of status for illnesses that possessed little clinical or
      laboratory specificity. Nevertheless, clinicians then and now have used symptom
      based diagnoses. Some of these diagnoses owe their existence as specific diseases
      to the norms and practices of an older era much different from our own. Others
      have not only thrived but have resisted plausible redefinition done by using more
      "objective" criteria. Many strategies, such as response-to-treatment arguments,
      quantitative methods (for example, factor analysis), and consensus conferences,
      have been used to find or confer specificity in symptom-based diagnoses. These
      strategies are problematic and have generally been used after symptom-based
      diagnoses have been recognized and defined. These historical observations
      emphasize that although biological and clinical factors have set boundaries for
      which symptoms might plausibly be linked in a disease concept, social influences
      have largely determined which symptom clusters have become diseases.

PMID- 11346315
TI  - Symptom research on chronic cough: a historical perspective.
AB  - This review provides a perspective on how research on the management of cough has
      evolved, looks at key methodologic lessons that have been learned from this
      research and how they may relate to the management of other symptoms, identifies
      important methodologic challenges that remain to be solved, and lists important
      questions that still need to be answered. Three important methodologic lessons
      have been learned. First, cough must be evaluated systematically and according to
      a neuroanatomic framework. Second, the response to specific therapy must be noted
      to determine the cause or causes of cough and to characterize the strengths and
      limitations of diagnostic testing. Third, multiple conditions can simultaneously
      cause cough. Among the three methodologic challenges that still need to be solved
      are 1) definitively determining the diagnostic accuracy and reliability of 24
      hour esophageal pH monitoring and how best to interpret pH test results, 2)
      definitively determining the role of nonacid reflux in cough due to
      gastroesophageal reflux disease, and 3) developing reliable and reproducible
      subjective and objective methods with which to assess the efficacy of cough
      therapy. Numerous important clinical questions are still unanswered: What role do
      empirical therapeutic trials play in diagnosing the cause of chronic cough? What
      is the most cost-effective approach to the diagnosis and treatment of chronic
      cough: empirical therapeutic trials or laboratory testing-directed therapeutic
      trials? How often is environmental air pollution, unrelated to allergies or
      smoking, responsible for chronic cough?

PMID- 11346316
TI  - Dyspepsia.
AB  - Dyspepsia refers to pain or discomfort centered in the upper abdomen. This
      symptom is remarkably common, with 1-year prevalence rates averaging 25% in the
      community. Symptoms suggestive of the irritable bowel syndrome and reflux disease
      frequently overlap but do not form part of the definition of dyspepsia.
      Electrical and other stimuli can cause similar or different symptoms in various
      patients, and even the site to which symptoms are referred varies considerably.
      Dyspeptic symptoms are therefore a relatively poor guide to the origin or nature
      of any "disturbances" in the gut. Identification of patients who require further
      investigation to rule out serious structural disease, such as peptic ulcer
      disease or cancer, is a key issue because unaided clinical diagnosis is
      unreliable. The use of an age threshold (typically 45 years) and the
      identification of alarm features, including weight loss, repeated vomiting, and
      signs of bleeding, seem to be valid on the basis of the limited evidence
      available. Dyspeptic symptoms fall into distinct subgroups resembling the
      perceived clinical entities of ulcer-like and dysmotility-like dyspepsia.
      Unfortunately, because of overlap with reflux symptoms and between the subgroups,
      the clinical significance of these groups remains highly questionable. A focus on
      symptom predominance may be more rewarding. Lack of validated outcome measures
      has hampered clinical studies and has led to the development of complex outcome
      measures that integrate and weigh different symptoms or other indirect indicators
      of outcome into a general score. Further testing and validation are in progress.

PMID- 11346317
TI  - Dizziness: state of the science.
AB  - Dizziness is prevalent in all adult populations, causing considerable morbidity
      and utilization of health services. In the community, the prevalence of dizziness
      ranges from 1.8% in young adults to more than 30% in the elderly. In the primary
      care setting, dizziness increases in frequency as a presenting complaint; as many
      as 7% of elderly patients present with this symptom. Classification of dizziness
      by subtype (vertigo, presyncope, disequilibrium, and other) assists in the
      differential diagnosis. Various disease entities may cause dizziness, and the
      reported frequency of specific diagnoses varies widely, depending on setting,
      patient age, and investigator bias. Life-threatening illnesses are rare in
      patients with dizziness, but many have serious functional impairment. Dizziness
      can be difficult to diagnose, particularly in elderly persons, in whom it often
      represents dysfunction in more than one body system. Given the relatively
      underdeveloped state of the empirical literature on dizziness, investigators
      would benefit from use of consistent criteria to describe dizziness symptoms and
      establish diagnoses. Investigation of the effects of testing and treatment should
      focus on diagnoses that are life threatening or lead to significant morbidity. In
      the elderly, a function-oriented approach should be studied and compared with
      current diagnosis-focused strategies. Alternative therapies for chronic and
      recurrent dizziness also merit investigation.

PMID- 11346318
TI  - Palpitations, arrhythmias, and awareness of cardiac activity.
AB  - Somatic and visceral symptoms have a surprisingly weak relationship to objective
      measures of tissue pathology. This is exemplified by the poor correlation found
      between palpitations and cardiac arrhythmias. Many factors other than extent of
      disease influence symptomatic distress, and since symptoms are such a crucial
      feature of illness and of medical practice, much more investigation of these
      nonbiomedical influences is needed. Although experimental laboratory paradigms
      facilitate such investigation, there are problems involved in generalizing from
      laboratory findings to the reporting of the symptoms of disease in daily life. In
      studying the awareness of cardiac arrhythmias and of resting heartbeat, we have
      found that the palpitations of patients who somatize more and have more health
      related anxiety and more psychiatric distress are significantly less likely to be
      related to demonstrable cardiac arrhythmias than are the palpitations of other
      patients. The accurate awareness of arrhythmias, however, is not associated with
      the accurate awareness of resting heartbeat. Even more surprising, a relatively
      large proportion of heart transplant recipients are accurately aware of their
      resting heartbeat. This work poses more questions than it answers. In so doing,
      it underscores some of the technical difficulties of conducting research in this
      area and shows how little is known about symptom perception, processing, and
      reporting.

PMID- 11346319
TI  - Chronic fatigue: symptom and syndrome.
AB  - Chronic fatigue is common, is difficult to measure, can be associated with
      considerable morbidity, and is rarely a subject of controversy. The chronic
      fatigue syndrome also presents problems in definition and measurement, is
      associated with even more morbidity than chronic fatigue itself, and is often
      controversial. Particularly unclear is the way in which chronic fatigue and the
      chronic fatigue syndrome relate to each other: Is one the severe form of the
      other, or are they qualitatively and quantitatively different? We know that many
      things can cause chronic fatigue, and this is probably true for the chronic
      fatigue syndrome, too. We can anticipate that discrete causes of the chronic
      fatigue syndrome will be found in the future, even if these causes are unlikely
      to fall neatly along the physical-psychological divide that some expect. The
      causes of chronic fatigue are undoubtedly many, both in a population and in any
      individual person, even when a discrete cause, such as depression or cancer, is
      identified. Social, behavioral, and psychological variables are important in both
      chronic fatigue and the chronic fatigue syndrome. Interventions that address
      these general variables can be successful, and currently they are often more
      successful than interventions directed at specific causes.

PMID- 11346320
TI  - Studying symptoms: sampling and measurement issues.
AB  - Physical symptoms account for more than half of all outpatient visits, but the
      specific causes and treatments of many common symptoms are frequently not well
      established. Because clinical research has primarily targeted specific diseases,
      symptoms-based research is still an emerging field of scientific inquiry, and
      optimal methods are still being developed. This paper considers eight important
      issues in sampling and measurement. First, recognition of the exceptionally high
      base rates of many symptoms is an essential primary step in selecting appropriate
      case-patients and controls. Second, the type of population studied (community,
      primary care clinic, subspecialty clinic, or symptom clinic) can greatly
      influence the severity and other characteristics of the symptom being evaluated.
      Third, symptom detection relies on three types of symptoms: documented, elicited,
      and volunteered. Fourth, temporal factors include recency of onset, episodicity,
      and duration. Fifth, severity can be assessed with single- or multiple-item
      symptom-specific scales as well as evaluation of generic functional status and
      health-related quality-of- life measures. Sixth, recognition of a symptom's cause
      can be strengthened by explicit criteria, uniform assessment protocols, and
      multiple raters. Seventh, comorbidity that should be assessed includes medical
      disorders, psychiatric disorders, and other symptoms. And eighth, since death and
      serious illness are uncommon, alternative outcomes that might be measured include
      symptom alleviation, health-related quality of life, patient and provider
      satisfaction, and health care costs.

PMID- 11346321
TI  - Associations of symptoms and health-related quality of life: findings from a
      national study of persons with HIV infection.
AB  - BACKGROUND: Health-related quality of life refers to how well people are able to
      perform daily activities (functioning) and how they feel about their lives (well
      being). The relationship between symptoms and health-related quality of life has
      not been fully explored. OBJECTIVE: To estimate the association of HIV symptoms
      with health-related quality of life and with disability days. DESIGN: Prospective
      cohort study. SETTING: HIV providers in 28 urban and 24 rural randomly selected
      sites throughout the United States. PATIENTS: Nationally representative sample of
      2267 adults with known HIV infection who were interviewed in 1996 and again
      between 1997 and 1998. MEASUREMENTS: Symptoms, two single-item global measures of
      health-related quality of life (perceived health and perceived quality of life),
      and disability days. RESULTS: White patches in the mouth; nausea or loss of
      appetite; persistent cough, difficulty breathing, or difficulty catching one's
      breath; and weight loss were associated with more disability days and worse
      scores on both health-related quality-of-life measures. Headache; pain in the
      mouth, lips, or gums; dry mouth; and sinus infection, pain, or discharge were
      associated with worse perceived health. Pain in the mouth, lips, or gums; trouble
      with eyes; pain, numbness, or tingling of hands or feet; and diarrhea or loose or
      watery stools were associated with worse perceived quality of life. Headache and
      fever, sweats, or chills were associated with more disability days. CONCLUSIONS:
      Several symptoms are associated with worse health-related quality of life and
      more disability days in persons with HIV infection. In such patients, targeting
      specific symptoms may improve health-related quality of life and reduce
      disability.

PMID- 11346322
TI  - Health-related quality of life and health care costs in severe, refractory
      irritable bowel syndrome.
AB  - BACKGROUND: The irritable bowel syndrome (IBS) may lead to considerable
      impairment of health-related quality of life and high health care costs. It is
      not clear whether these poor outcomes directly result from severe bowel symptoms
      or reflect a coexisting psychiatric disorder. OBJECTIVE: To determine whether
      bowel symptom severity and psychological symptoms directly influence health
      related quality of life and health care costs. DESIGN: Cross-sectional survey.
      SETTING: Secondary and tertiary gastroenterology clinics. PATIENTS: 257 patients
      with severe IBS who did not respond to usual treatments and were recruited for a
      trial of psychological treatment. MEASUREMENTS: Predictors were abdominal pain,
      entries in a diary of 10 IBS symptoms, and measures of psychological symptoms.
      Outcomes were inability to work, health-related quality of life (measured by
      Medical Outcomes Survey 36-item short-form questionnaire [SF-36] physical
      component summary scores), and health care and productivity costs. Predictor and
      outcome measures were compared by using multiple regression and logistic
      regression analyses. RESULTS: Abdominal pain occurred on average 24 days per
      month and activities were restricted on 145 days of the previous 12 months. The
      mean (+/-SD) Hamilton depression score was 11.3 +/- 6.1. The SF-36 physical
      component summary score was low (37.7 +/- 10.6), and the patients had incurred
      high health care costs ($1743 +/- $2263) over the previous year. Global severity
      and somatization scores on the Symptom Checklist 90 Revised, abdominal pain, and
      Hamilton depression scores independently contributed to the physical component
      score of the SF-36 (adjusted R(2) = 35.2%), but only psychological scores were
      associated with disability due to ill health. These variables did not accurately
      predict health care or other costs (adjusted R(2) = 9.3%). History of sexual
      abuse was not an independent predictor of outcome. CONCLUSIONS: Both abdominal
      and psychological symptoms are independently associated with impaired health
      related quality of life in patients with severe IBS. Optimal treatment is likely
      to require a holistic approach. Since health care and loss of productivity costs
      are not clearly associated with these symptoms, alleviation of them will not
      necessarily lead to reduced costs.

PMID- 11346323
TI  - A review of the evidence for overlap among unexplained clinical conditions.
AB  - PURPOSE: Unexplained clinical conditions share features, including symptoms
      (fatigue, pain), disability out of proportion to physical examination findings,
      inconsistent demonstration of laboratory abnormalities, and an association with
      "stress" and psychosocial factors. This literature review examines the nature and
      extent of the overlap among these unexplained clinical conditions and the
      limitations of previous research. DATA SOURCES: English-language articles were
      identified by a search of the MEDLINE database from 1966 to January 2001 by using
      individual syndromes and their hallmark symptoms as search terms. STUDY
      SELECTION: Studies that assessed patients with at least one unexplained clinical
      condition and that included information on symptoms, overlap with other
      unexplained clinical conditions, or physiologic markers. Conditions examined were
      the chronic fatigue syndrome, fibromyalgia, the irritable bowel syndrome,
      multiple chemical sensitivity, temporomandibular disorder, tension headache,
      interstitial cystitis, and the postconcussion syndrome. DATA EXTRACTION:
      Information on authorship, patient and control groups, eligibility criteria, case
      definitions, study methods, and major findings. DATA SYNTHESIS: Many similarities
      were apparent in case definition and symptoms, and the proportion of patients
      with one unexplained clinical condition meeting criteria for a second unexplained
      condition was striking. Tender points on physical examination and decreased pain
      threshold and tolerance were the most frequent and consistent objective findings.
      A major shortcoming of all proposed explanatory models is their inability to
      account for the occurrence of unexplained clinical conditions in many affected
      patients. CONCLUSIONS: Overlap between unexplained clinical conditions is
      substantial. Most studies are limited by methodologic problems, such as case
      definition and the selection and recruitment of case-patients and controls.

PMID- 11346324
TI  - Measuring patients' expectations and requests.
AB  - Patients seeking help for symptoms frequently worry about the underlying causes
      of their symptoms; have specific expectations for care; and request (or demand)
      time, information, and services. Understanding patients' concerns, expectations,
      and requests is important for clinicians, health care policymakers, and
      researchers. One obstacle to progress in this area has been disagreement over the
      most appropriate methods for identifying, monitoring, and classifying these
      phenomena. This article reviews the conceptual relationships linking patients'
      expectations, requests, and satisfaction with care; surveys contemporary
      approaches to the measurement of expectations and requests; and highlights recent
      empirical findings. The literature reviewed supports the conclusion that
      patients' expectations are wide ranging, can be measured, and have potentially
      important clinical consequences. For clinicians and policymakers alike, learning
      to elicit, evaluate, and understand patients' expectations will be a major task
      for the early part of the new century.

PMID- 11346325
TI  - The effect of unmet expectations among adults presenting with physical symptoms.
AB  - BACKGROUND: Unmet patient expectations are common and have been associated with
      decreased patient satisfaction. OBJECTIVE: To assess the prevalence and effect of
      unmet expectations in patients presenting with physical symptoms. DESIGN:
      Prospective cohort study. SETTING: Primary care walk-in clinic. Most patients
      were seeing a particular provider for the first time. PATIENTS: 750 adults whose
      principal reason for the clinic visit was a physical symptom. MEASUREMENTS:
      Patients completed previsit questionnaires that assessed symptom characteristics,
      the patient's expectations of the visit, functional status (Medical Outcomes
      Study Short Form-6), and mental disorders (Primary Care Evaluation of Mental
      Disorders [PRIME-MD]). Patient questionnaires given immediately after the visit
      and 2 weeks after the visit assessed patient satisfaction with the visit and
      unmet expectations; the 2-week questionnaire also assessed symptom outcome and
      functional status. Postvisit physician questionnaires measured encounter
      difficulty (Difficult Doctor Patient Relationship Questionnaire) and what the
      physician did in response to the patient's symptom. RESULTS: Nearly all patients
      (98%) had at least one previsit expectation, including a diagnosis (81%), an
      estimate of how long the symptom was likely to last (63%), a prescription (60%),
      a diagnostic test (54%), and a subspecialty referral (45%). Immediately after the
      visit, the most common unmet expectations were for prognostic information (51%)
      or diagnostic information (33%). Only 11% of patients had an unmet expectation of
      a diagnostic test, subspecialty referral, prescription, or sick slip. Unmet
      patient expectations were more common after encounters experienced as difficult
      by the clinician and in patients with underlying mental disorders. Patients with
      no unmet expectations had less worry about serious illness (54% vs. 27%; P <
      0.001) and greater satisfaction (59% vs. 19%; P < 0.001), and patients who
      reported receiving diagnostic or prognostic information were more likely to have
      symptom alleviation (relative risk, 1.2 [95% CI, 1.02 to 1.3]) and functional
      improvement (functional status score, 25 vs. 23; P = 0.01) at 2 weeks.
      CONCLUSIONS: Patients who seek care for physical symptoms and do not leave the
      encounter with an unmet expectation are more likely to be satisfied with their
      care and to have less worry about serious illness. Diagnostic and prognostic
      information are particularly valued by patients and may be associated with
      greater improvement in symptoms and functional status 2 weeks after the visit.

PMID- 11346326
TI  - Physical symptoms and physician-experienced difficulty in the physician-patient
      relationship.
AB  - BACKGROUND: The practice of medicine has many expected and accepted challenges,
      but all physicians experience some patients as difficult to a degree that
      transcends these expectations. Physician-experienced difficulty is associated
      with a syndrome of three characteristics: patient psychopathology, abrasive
      interpersonal styles, and multiple physical symptoms. OBJECTIVE: To assess the
      roles played by the number of physical symptoms and by specific symptoms in
      determining whether physician-experienced difficulty occurs. DESIGN: New analyses
      of epidemiologic survey data from the Primary Care Evaluation of Mental Disorders
      (PRIME-MD) 1000 Study. SETTING: Four primary care clinics. PARTICIPANTS: 627
      ambulatory patients seen by 27 physicians. MEASUREMENTS: Physician-experienced
      difficulty was measured by using the 10-item Difficult Doctor Patient
      Relationship Questionnaire (DDPRQ-10); patient-reported physical symptoms and
      physician-assessed psychopathology and somatoform symptoms were evaluated by
      using the PRIME-MD; and physical illnesses were measured by using a physician
      questionnaire. RESULTS: The number of physical symptoms and the number of
      somatoform symptoms correlated with difficulty (r = 0.39 and r = 0.37,
      respectively; P < 0.001), and the correlations remained significant after
      adjustment for physical and mental disorders (r = 0.20 for both correlations; P <
      0.001). Difficult patients were more likely to have each of 16 physical symptoms;
      the odds of being difficult were greater for patients with 1 of 5 particular
      symptoms (stomach pain, fainting, loose stools/diarrhea, palpitations, and sleep
      problems), even after adjustment for physical and mental disorders. All 10 items
      on the DDPRQ-10 were influenced by physical symptoms, particularly those items
      that asked about physician frustration and whether patients were manipulative and
      time consuming. CONCLUSIONS: The association between physical symptoms and
      difficulty is due in part to the association between physical symptoms and mental
      disorders, but symptoms also contribute independently to difficulty. The
      independent component of symptom-associated difficulty may be due to 1)
      differences between patient and physician in expectations about treatment and 2)
      the part that symptoms play in conferring the "sick role" on a patient.

PMID- 11346327
TI  - Symptom management in older primary care patients: feasibility of an
      experimental, written self-disclosure protocol.
AB  - BACKGROUND: Distress-driven symptoms are prevalent among older primary care
      patients and account for a large percentage of office visits and increased
      medical costs. An experimental written self-disclosure protocol has been shown to
      reduce symptoms and use of health care services in healthy adults. Written self
      disclosure as a method for reducing symptoms has not been evaluated in the
      primary care setting. OBJECTIVE: To evaluate the feasibility of adapting an
      experimental written self-disclosure protocol for the primary care setting.
      DESIGN: Randomized, single-blind feasibility study. SETTING: University-based
      geriatric and internal medicine primary care clinics. PATIENTS: 45 patients 66
      years of age or older without a psychiatric diagnosis. INTERVENTION: Three 20
      minute writing sessions focusing on distressing experiences (in the intervention
      group) or health behaviors (in the control group). MEASUREMENTS: The feasibility
      outcomes were patient recruitment, protocol logistics, and patient and provider
      satisfaction. The clinical outcomes were somatic and distress symptoms, health
      care utilization, and associated costs. RESULTS: One third of patients screened
      were recruited; 96% of patients recruited completed the protocol. Clinic contact
      time was an average of 55 minutes per patient. Patients and providers reported
      high levels of satisfaction with the protocol. Reductions in symptoms were
      minimal for both groups. Use of outpatient services and associated costs
      decreased in both groups, but the reduction was twice as great in the treatment
      group as in the control group. CONCLUSIONS: Findings support the feasibility of
      implementing the protocol as a primary care intervention.

PMID- 11346328
TI  - Stepped care for back pain: activating approaches for primary care.
AB  - Interventions that encourage return to normal function and reduce fear of
      physical activity have been shown to improve outcomes for patients with back
      pain, but routine medical care for back pain often does not provide such
      interventions. This paper proposes a stepped-care approach that addresses the
      functional outcomes of back pain. Step 1, which is relevant to most patients,
      addresses the common fears of patients with back pain and encourages patients to
      resume normal activities. Step 2, which targets the substantial minority of
      patients who require more than simple advice to resume activities, provides
      brief, structured interventions that support physical exercise and return to
      normal activities. Step 3 targets patients who require more intensive
      interventions, including treatment of psychological illness when present, before
      they can return to normal activities in work and family life. Patient needs
      relevant to these three levels of care are delineated. This stepped-care approach
      provides a framework for sequencing progressively more intensive interventions
      and coordinating the efforts of primary care physicians, allied health
      professionals, behavioral health clinicians, and patients to improve functional
      outcomes in patients with back pain.

PMID- 11346329
TI  - Medical symptoms without identified pathology: relationship to psychiatric
      disorders, childhood and adult trauma, and personality traits.
AB  - Community studies have shown that stressful life events, psychological distress,
      and depressive and anxiety disorders are associated with 1) a range of medical
      symptoms without identified pathology, 2) increased health care utilization, and
      3) increased costs. In both primary care and medical specialty samples, patients
      who have syndromes with ill-defined pathologic mechanisms (such as the irritable
      bowel syndrome and fibromyalgia) have been shown to have significantly higher
      rates of anxiety and depressive disorders than do patients with comparable, well
      defined medical diseases and similar symptoms. Other studies show that after
      adjustment for severity of medical illness, patients with depression or anxiety
      and comorbid medical disease have significantly more medical symptoms without
      identified pathology than do patients with a similar medical disease alone. Both
      childhood maltreatment and psychological trauma in adulthood have been associated
      with increased vulnerability to psychiatric illness and more medical symptoms.
      The substantial functional impairment, distress, and costs associated with
      medical symptoms without identified pathology suggest that research studies
      promoting a better understanding of the biopsychosocial cause of these symptoms
      may yield pragmatic, cost-effective approaches to treatment in medical settings.

PMID- 11346330
TI  - "Unexplained" somatic symptoms, functional syndromes, and somatization: do we
      need a paradigm shift?
AB  - Medically unexplained functional or somatization symptoms are somatic disorders
      that are not adequately explained by physical disease processes. The way in which
      these disorders have been understood and managed has varied over the history of
      medicine. However, only in the past 100 years has the "mental" explanation
      predominated. A benefit of this trend has been the development of effective
      treatments in the form of "antidepressant" drugs and cognitive-behavioral
      therapies; a cost has been limited integration of these treatments into medical
      practice and lack of acceptability to patients. We suggest that there is much to
      learn from physicians of the pre-Freudian era. Their etiologic theories are now
      supported by new scientific evidence, and their clinical practice provided ways
      of making psychological treatment acceptable to patients. We propose a paradigm
      shift in which unexplained symptoms are remedicalized around the notion of a
      functional disturbance of the nervous system and treatments currently considered
      "psychiatric" are integrated into general medical care.

PMID- 11346331
TI  - On first looking into Pernkopf's atlas (part 1).

PMID- 11346332
TI  - Lichen amyloidosis associated with atopic dermatitis: clinical resolution with
      cyclosporine.

PMID- 11346333
TI  - A unique microvascular phenotype shared by juvenile hemangiomas and human
      placenta.
AB  - BACKGROUND: Juvenile hemangiomas are common, benign tumors, distinctive for their
      perinatal presentation, rapid growth during the first year of life, and
      subsequent involution. We recently reported that endothelia of hemangiomas highly
      express GLUT1, a glucose transporter normally restricted to endothelia with blood
      tissue barrier function, as in brain and placenta. OBJECTIVE: To investigate
      possible further similarities between hemangioma and placental vessels. DESIGN:
      In a retrospective study of a variety of vascular tumors and anomalies, we
      assessed lesional immunoreactivities for the placenta-associated vascular
      antigens FcgammaRII, Lewis Y antigen (LeY), merosin, and GLUT1. SETTING: A
      university-affiliated pediatric hospital. MAIN OUTCOME MEASURE:
      Immunoreactivities scored for each antigen were summarized according to lesional
      type, compared with those of normal skin, brain, and placenta, and correlated
      with patient age, sex, and lesional location. RESULTS: All of 66 hemangiomas
      (patients aged 22 days to 7 years) showed intense immunoreactivity for
      FcgammaRII, merosin, LeY, and GLUT1. No immunoreactivities for these markers were
      seen in any of 26 vascular malformations, 4 granulation tissue specimens, 13
      pyogenic granulomas, or in the tumor vasculature of 6 malignant tumors of
      nonvascular origin. Microvascular immunoreactivity for all 4 markers was observed
      in placental chorionic villi, but was absent in microvessels of normal skin and
      subcutis. Brain microvessels expressed only GLUT1 and merosin. CONCLUSIONS: A
      distinct constellation of tissue-specific markers is uniquely coexpressed by
      hemangiomas and placental microvessels. These findings imply a unique
      relationship between hemangioma and the placenta and suggest new hypotheses
      concerning the origin of these tumors.

PMID- 11346335
TI  - Infantile hemangiomas: speculation on placental trophoblastic origin.
AB  - BACKGROUND: The unique immunobiology of the placental trophoblast and the
      increased incidence of hemangiomas in infants born after chorionic villus
      sampling suggest that an immunologically regulated ectopic focus of trophoblasts
      could be the cell of origin for proliferative infantile hemangiomas. OBJECTIVE:
      To compare tissue from infantile hemangiomas with that of other vascular lesions
      for the presence of selected placental trophoblast-specific cellular markers.
      DESIGN AND PATIENTS: Twelve tissue specimens taken from infantile hemangiomas on
      patients aged 5 days to 2 years were retrospectively confirmed clinically and
      histologically. Negative controls were similarly confirmed, including 6 pyogenic
      granulomas and 4 vascular-lymphatic malformations. These tissues were used for
      immunohistochemical analysis of selected trophoblastic markers including human
      placental lactogen, placental alkaline phosphatase, and cytokeratins 7, 8, and
      17. SETTING: Tissue submitted from patients seen at Saint Louis University
      Department of Dermatology and Cardinal Glennon Children's Hospital in St Louis,
      Mo, between January 1, 1997, and October 31, 1999. MAIN OUTCOME MEASURE:
      Differential staining for trophoblastic markers in infantile hemangiomas compared
      with control tissues. RESULTS: The 12 infantile hemangiomas were uniformly
      negative for all markers tested. Control tissues were also negative for these
      markers. Four of the 5 histochemical markers did recognize specific nonvascular,
      cutaneous elements: placental alkaline phosphatase stained smooth and striated
      muscle, cytokeratins 7 and 8 stained eccrine glands, and cytokeratin 17 stained
      pilosebaceous units. CONCLUSIONS: Our results do not support the placental
      trophoblast as the cell of origin for infantile hemangiomas, but we hope our
      observations and speculation will stimulate further study of this hypothesis.

PMID- 11346336
TI  - Phase 2 and 3 clinical trial of oral bexarotene (Targretin capsules) for the
      treatment of refractory or persistent early-stage cutaneous T-cell lymphoma.
AB  - OBJECTIVES: To determine the safety and efficacy of oral bexarotene (Targretin
      capsules; Ligand Pharmaceuticals Incorporated, San Diego, Calif). DESIGN: The
      effects of 2 randomized doses of 6.5 mg/m(2) per day (with crossover for
      progression) vs 650 mg/m(2) per day (later modified to 300 mg/m(2) per day) were
      evaluated in an open-label, multicenter, phase 2 and 3 study conducted between
      February 1997 and November 1998. SETTING: Eighteen international cutaneous T-cell
      lymphoma clinics at academic referral centers. PATIENTS: Fifty-eight patients
      with biopsy-proven stage IA through IIA cutaneous T-cell lymphoma that was
      refractory to (or patients were intolerant of) treatment or had reached at least
      a 6-month response plateau under at least 2 forms of prior therapy (median of 3.5
      prior therapies). INTERVENTION: Bexarotene (Targretin capsules) administered once
      daily with meal for 16 weeks or longer. MAIN OUTCOME MEASURES: Primary end point
      classification of overall response rate of complete and partial remissions
      determined by either the Physician's Global Assessment of Clinical Condition or
      the objective Composite Assessment of Index Lesion Severity. Body surface area,
      time to response, duration of disease control, time to disease progression,
      individual index lesion signs and symptoms, and quality of life parameters were
      secondary outcomes. RESULTS: Responses (> or = 50% improvement) were seen in 3
      (20%) of 15 patients with an initial dose at 6.5 mg/m(2) per day (95% confidence
      interval [CI], 0%-40%), 15 (54%) of 28 patients at 300 mg/m(2) per day (95% CI,
      35%-72%), and 10 (67%) of 15 patients at above 300 mg/m(2) per day (95% CI, 43%
      91%). The rate of progressive disease was 47%, 21%, and 13% at the same dose
      levels, respectively. Eight (73%) of 11 patients crossing over from 6.5 mg/m(2)
      per day to higher doses subsequently responded. The median duration of response
      from start of therapy could not be estimated for the 15 patients at 300 mg/m(2)
      per day owing to low relapse rates in 2 patients (13%); at higher doses it was
      516 days. The following drug-related adverse effects were reversible and
      treatable: hypertriglyceridemia (46 patients [79%]), hypercholesterolemia (28
      patients [48%]), headache (27 patients [47%]), central hypothyroidism (23
      patients [40%]), asthenia (21 patients [36%]), and leukopenia (16 patients
      [28%]). No cases of drug-related neutropenic fever, sepsis, or death occurred.
      Pancreatitis occurred in 3 patients with triglyceride levels higher than 14.69
      mmol/L (1300 mg/dL), all of whom were taking 300 mg/m(2) or more of oral
      bexarotene per day. CONCLUSIONS: Bexarotene (Targretin capsules) (the first
      retinoid X receptor-selective rexinoid) was well tolerated and effective as an
      oral treatment for 15 (54%) of 28 patients with refractory or persistent early
      stage cutaneous T-cell lymphoma at doses of 300 mg/m(2) per day.
      Hypertriglyceridemia and hypothyroidism require monitoring but are reversible and
      manageable with concomitant medication.

PMID- 11346337
TI  - Factor V Leiden mutation in postthrombotic and non-postthrombotic venous ulcers.
AB  - OBJECTIVE: To determine the prevalence of the factor V Leiden mutation in
      patients with postthrombotic and non-postthrombotic venous ulcers. DESIGN: Case
      control study. SETTING: Department of Dermatology, University Hospital of Zurich,
      Zurich, Switzerland. PARTICIPANTS: Seventy-three consecutive outpatients and
      inpatients with venous ulcers and 45 age- and sex-matched control subjects
      (matched to the 42 patients with postthrombotic syndrome). MAIN OUTCOME MEASURES:
      Frequency of postthrombotic and non-postthrombotic findings in patients with
      venous ulcers. Prevalence of the factor V Leiden mutation in these different
      subgroups. RESULTS: Postthrombotic syndrome was identified as the cause of 42
      (58%; 95% confidence interval [CI], 45%-69%) of 73 venous ulcers, and the
      remainder were caused by primary valvular insufficiency. In postthrombotic
      ulcers, the prevalence of the factor V Leiden mutation was 38% (95% CI, 24%-54%)
      (16/42), which corresponds to an odds ratio of 13.2 (95% CI, 2.8-62.3; P<.001).
      In non-postthrombotic venous ulcers, the prevalence was 16% (95% CI, 5%-34%)
      (5/31), which corresponds to an odds ratio of 3.2 (95% CI, 1.0-10.0; P =.07).
      CONCLUSIONS: The factor V Leiden mutation is highly prevalent in patients with
      postthrombotic venous ulcers. Even patients with non-postthrombotic venous ulcers
      show a moderately elevated prevalence of the factor V Leiden mutation. Some of
      the latter might be misclassified because of near-to-perfect revascularization
      after asymptomatic deep venous thrombosis. However, as long as the therapeutic
      consequences of the factor V Leiden mutation are not established, systematic
      screening cannot be recommended in patients with venous ulcers.

PMID- 11346338
TI  - Ganglion of the distal interphalangeal joint (myxoid cyst): therapy by
      identification and repair of the leak of joint fluid.
AB  - BACKGROUND: Digital myxoid cysts are a relatively common pathology in the skin,
      representing a ganglion of the adjacent distal interphalangeal joint. Success of
      treatment is largely proportional to the destructiveness of the therapy and
      postoperative morbidity. We studied an effective, minimally traumatic surgical
      treatment in which tissue is not removed and morbidity is low. DESIGN: Open,
      nonrandomized trial of therapy. Methylene blue dye was injected into the distal
      interphalangeal joint. A skin flap was designed around the cyst and raised to
      identify the dye-filled communication between joint and cyst. The communication
      was sutured and the flap was replaced with no tissue excision. SETTING: Two
      university dermatology departments. PATIENTS: Fifty-four subjects with 47 cysts
      involving fingers or thumbs and 7 involving toes. Previous therapies in 37
      patients had resulted in relapse. MAIN OUTCOME MEASURES: Clinical assessment at 2
      and 8 months. RESULTS: We treated 34 women and 20 men (mean age, 60.4 years;
      range, 45-83 years). Communication between cyst and joint was identified by means
      of methylene blue injection in 48 patients (89%). At 8 months, 48 patients
      remained cured with no visible scarring. Of these, nail dystrophy associated with
      the cyst preoperatively (n = 35) resolved in all but 1 patient (97%). Six
      patients had relapses (5 within 4 months). Of these, 3 were on the toes. Cure
      rate on toes was 4 of 7 (57%) and on fingers, 44 of 47 (94%). In 2 patients, pain
      persisted for 4 months and then resolved. Limitation of joint mobility resolved
      after 2 months in 1 subject. CONCLUSIONS: Ligature of myxoid cyst origin at the
      joint capsule is an effective treatment and does not require excision. Myxoid
      cysts on toes are more likely to relapse than those on fingers.

PMID- 11346339
TI  - Clinical and pathophysiologic correlates of 1064-nm Nd:Yag laser treatment of
      reticular veins and venulectasias.
AB  - BACKGROUND: The goal of sclerotherapy, laser therapy, and intense pulsed-light
      therapy is to produce long-term, cosmetically significant elimination of
      disfiguring leg veins. This study examines the histologic and clinical effects of
      using a 1064-nm Nd:YAG laser system on lower extremity vessels. DESIGN: A single
      treatment using the following parameters: wavelength, 1064 nm (multiple
      synchronized pulsing); spot size, 6 mm; pulse duration, 14 milliseconds (single
      pulse); and fluence, 130 J/cm(2). SETTING: Private dermatology practice.
      PATIENTS: Thirteen women (mean age, 38.5 years) with blue venulectasia, 0.5 to
      1.5 mm in diameter (class 2), and reticular veins, 1.5 to 3.0 mm in diameter
      (class 3), on the thighs. MAIN OUTCOME MEASURES: Examination of treated and
      untreated areas by 2 masked observers using macrophotography (1, 2, 3, and 6
      months after treatment), Doppler, and optical chromatographic changes. Findings
      from three 2-mm punch biopsies from treated (immediately and 4 weeks after
      treatment) and untreated sites. Routine histologic examination; special stains
      (for elastic and connective tissue and for mucopolysaccharides); and
      immunohistochemical analysis for expression of the heat shock protein hsp70, tie2
      (an endothelial cell-specific receptor tyrosine kinase), and transforming growth
      factors beta1 and beta2. RESULTS: Eight patients (62%) manifested 75% to 100%
      clearing of treated vessel surface area. Treated areas revealed perivascular
      hemorrhage, thrombi, fragmentation and homogenization of elastic fibers, and
      eosinophilia of vessel walls. Expression of hsp70 and transforming growth factor
      beta was increased in treated vessels. CONCLUSIONS: Our data confirm the
      effectiveness of 1064-nm Nd:YAG laser treatment in clearing dilated lower
      extremity veins, probably by heat-induced vessel damage and subsequent fibrosis.
      Maintenance of clearing was achieved for up to 6 months. However, the presence of
      recanalized thrombi in some of the specimens suggests the potential for long-term
      vessel reappearance.

PMID- 11346340
TI  - Epithelial-mesenchymal interactions in wounds: treatment of palmoplantar wounds
      by nonpalmoplantar pure epidermal sheet grafts.
AB  - BACKGROUND: Palms and soles differ from other body sites in terms of clinical and
      histologic appearance and response to mechanical stress. We previously reported
      that palmoplantar fibroblasts regulate keratin 9, which is a marker of palms and
      soles. OBJECTIVE: To treat palmoplantar wounds by using nonpalmoplantar pure
      epidermal sheets as a graft. DESIGN: Nonrandomized controlled trials. SETTING:
      University dermatology and plastic surgery services. PATIENTS: Forty-eight
      patients with palmoplantar wounds caused by burns, trauma, chronic ulcers, and
      the resection of malignant tumors, such as squamous cell carcinoma and acral
      lentiginous melanoma. INTERVENTIONS: The patients received nonpalmoplantar pure
      epidermal sheet grafts (n = 14), nonpalmoplantar donor site skin grafts (n = 17),
      or palmoplantar donor site skin grafts (n = 17). MAIN OUTCOME MEASURES: Clinical
      and histologic findings. RESULTS: The pure epidermal sheets were successfully
      grafted and gradually demonstrated the adoption of a palmoplantar phenotype when
      reticular dermis of the recipient site remained. The epidermis showed
      hyperkeratosis and acanthosis by histologic studies and stained positively for
      keratin 9 in all of the suprabasal keratinocyte layers like palmoplantar-type
      skin. Pure epidermal sheets were placed on deeper wounds after the wounds had an
      artificial dermis applied and adopted the palmoplantar phenotype without erosions
      and ulcerations. Neither nonpalmoplantar split-thickness nor full-thickness skin
      grafts resulted in a palmoplantar phenotype. CONCLUSIONS: Pure epidermal sheet
      grafting would be useful for the treatment of palmoplantar wounds as
      nonpalmoplantar epidermis is much easier to obtain clinically. In addition,
      secondary procedures are not required to repair the donor site, since this wound
      is superficial.

PMID- 11346341
TI  - Kwashiorkor in the United States: fad diets, perceived and true milk allergy, and
      nutritional ignorance.
AB  - BACKGROUND: Kwashiorkor is the edematous form of protein-energy malnutrition. It
      is associated with extreme poverty in developing countries and with chronic
      malabsorptive conditions such as cystic fibrosis in developed countries. Rare
      cases of kwashiorkor in affluent countries unrelated to chronic illness have been
      reported. We present 12 cases of kwashiorkor unrelated to chronic illness seen
      over 9 years by pediatric dermatologists throughout the United States, and
      discuss common causative themes in this easily preventable condition.
      OBSERVATIONS: Twelve children were diagnosed as having kwashiorkor in 7 tertiary
      referral centers throughout the United States. The diagnoses were based on the
      characteristic rash and the overall clinical presentation. The rash consisted of
      an erosive, crusting, desquamating dermatitis sometimes with classic "pasted-on"
      scale-the so-called flaky paint sign. Most cases were due to nutritional
      ignorance, perceived milk intolerance, or food faddism. Half of the cases were
      the result of a deliberate deviation to a protein-deficient diet because of a
      perceived intolerance of formula or milk. Financial and social stresses were a
      factor in only 2 cases, and in both cases social chaos was more of a factor than
      an absolute lack of financial resources. Misleading dietary histories and the
      presence of edema masking growth failure obscured the clinical picture in some
      cases. CONCLUSIONS: Physicians should consider the diagnosis of kwashiorkor in
      children with perceived milk allergies resulting in frequent dietary
      manipulations, in children following fad or unorthodox diets, or in children
      living in homes with significant social chaos. The presence of edema and "flaky
      paint" dermatitis should prompt a careful dietary investigation.

PMID- 11346343
TI  - A new rexinoid for cutaneous t-cell lymphoma.

PMID- 11346342
TI  - Hair diameter diversity: a clinical sign reflecting the follicle miniaturization.
AB  - BACKGROUND: The degree of androgenetic alopecia is generally evaluated either by
      global clinical scales or time-consuming methods like phototrichogram or
      histological studies. We describe a new clinical and reliable scoring method
      based on hair diameter diversity. OBSERVATIONS: (1) The clinical macroscopic
      scoring we propose for hair density was significantly correlated with Hamilton
      classification and with histological hair density. (2) Diversity in hair diameter
      was the main and most accurate clinical parameter linked to follicle
      miniaturization. (C) The anagen-telogen ratio decreased in parallel with the
      decrease in clinical hair density score. CONCLUSIONS: Considering that hair
      follicle miniaturization is the key point during androgenic alopecia onset and
      development, diversity in hair diameter represents an important feature to
      consider as an accurate clinical sign reflecting hair follicle miniaturization.
      Moreover, diversity in hair diameter seems to be an easily accessible and
      reliable parameter that should be taken into consideration for further
      characterization of hair disorders. By itself, we believe that this clinical
      feature constitutes a new tool of substantial help for the diagnosis and
      management of androgenic alopecia.

PMID- 11346344
TI  - Off-center fold: noninflammatory, fluctuant swelling of the ear. Pseudocyst of
      auricle.

PMID- 11346345
TI  - Off-center fold: gradually enlarging bilateral facial nodules. Apocrine
      hidrocystoma.

PMID- 11346346
TI  - Off-center fold: asymptomatic follicular papules with alopecia on the lower part
      of the leg. Follicular mycosis fungoides.

PMID- 11346347
TI  - Off-center fold: generalized flesh-colored pouchlike papules. Anteoderma.

PMID- 11346349
TI  - Dermatologic surgeons will determine what's in their name: both high quality and
      high standards.

PMID- 11346350
TI  - On the importance of definition in dermatology and all fields of human endeavor.

PMID- 11346351
TI  - Green tea polyphenols may be useful in the treatment of androgen-mediated skin
      disorders.

PMID- 11346352
TI  - Are porokeratoses an infection?

PMID- 11346353
TI  - Dominant dystrophic epidermolysis bullosa associated with pyloric stenosis and
      congenital absence of skin.

PMID- 11346354
TI  - Imiquimod: a new possibility for treatment-resistant verrucae planae.

PMID- 11346355
TI  - Cutaneous leishmaniasis due to Leishmania infantum in the northeast of Spain: the
      isoenzymatic analysis of parasites.

PMID- 11346356
TI  - Cutaneous intolerance to tattoos in a patient with human immunodeficiency virus:
      a manifestation of the immune restoration syndrome.

PMID- 11346357
TI  - Efficacy and safety of topical atropine in treatment of multiple eccrine
      hidrocystomas.

PMID- 11346358
TI  - Diabetic foot ulcers and Chlamydia pneumoniae: innocent bystander or
      opportunistic pathogen?

PMID- 11346359
TI  - Hyper-IgE, eosinophilia, and immediate cutaneous hypersensitivity to insect
      antigens in the pruritic papular eruption of human immunodeficiency virus.

PMID- 11346360
TI  - "Easy dressing": an economical, transparent nonporous film for wound care after
      laser resurfacing.

PMID- 11346361
TI  - Carbamazepine-induced, CD30+, primary, cutaneous, anaplastic large-cell lymphoma.

PMID- 11346364
TI  - Amyotrophic lateral sclerosis: the search for a spectroscopic marker of upper
      motoneuron involvement.

PMID- 11346365
TI  - Acute severe spinal cord dysfunction in bacterial meningitis in adults: MRI
      findings suggest extensive myelitis.

PMID- 11346366
TI  - Therapeutic interventions following mammalian spinal cord injury.

PMID- 11346367
TI  - Proton magnetic resonance spectroscopy of the motor cortex in 70 patients with
      amyotrophic lateral sclerosis.
AB  - OBJECTIVE: To evaluate proton magnetic resonance spectroscopy for detection and
      monitoring of upper motoneuron degeneration in patients with amyotrophic lateral
      sclerosis. METHODS: Seventy patients with amyotrophic lateral sclerosis according
      to the El Escorial criteria were compared with 48 healthy control subjects.
      Single-volume proton magnetic resonance spectroscopy (echo time, 272
      milliseconds; repetition time, 2000 milliseconds) was performed in both motor
      cortices for detection of N-acetylaspartate (NAA), phosphocreatine + creatine
      ([P]Cr), and choline-containing compounds (Cho) to calculate the metabolite
      ratios NAA/Cho, NAA/(P)Cr, and Cho/(P)Cr. In addition, absolute metabolite
      concentrations of NAA, (P)Cr, and Cho were obtained in 30 patients and 15
      controls with the unsuppressed water signal used as an internal reference.
      RESULTS: Absolute concentrations of NAA (P<.001) and (P)Cr (P<.05) were reduced
      in motor cortices of patients, whereas Cho concentrations remained unchanged. The
      NAA/Cho and NAA/(P)Cr ratios were reduced in all El Escorial subgroups (P<.001).
      The Cho/(P)Cr ratio was elevated in patients with definite amyotrophic lateral
      sclerosis (P<.05). Metabolite ratio changes corresponded to the lateralization of
      clinical symptoms and were weakly correlated with disease duration and disease
      severity. In follow-up observations of 16 patients during a mean (+/-SD) of 12.1
      +/- 8.7 months, NAA/Cho dropped by 9.1% (P<.01), and Cho/(P)Cr increased by 7.0%
      (P<.01). Changes of metabolite ratios were significantly correlated with
      progression of disease severity. CONCLUSIONS: Measurement of NAA concentrations
      and NAA/Cho ratios appear to be most suitable for detection of motor cortex
      degeneration by single-volume proton magnetic resonance spectroscopy. Reduced
      NAA/Cho ratios correspond to aspects of the clinical presentation and reflect
      disease progression in follow-up measurements.

PMID- 11346368
TI  - Familial amyotrophic lateral sclerosis with a novel Leu126Ser mutation in the
      copper/zinc superoxide dismutase gene showing mild clinical features and lewy
      body-like hyaline inclusions.
AB  - BACKGROUND: Mutations in the SOD1 gene are responsible for approximately 25% of
      all familial amyotrophic lateral sclerosis (ALS) cases. However, the correlation
      between the clinical and pathological features and the various SOD1 gene
      mutations has not been well characterized. OBJECTIVES: To screen the SOD1 gene in
      search of potential mutations and to obtain clinical and pathological data for 2
      Japanese families with ALS. DESIGN: Clinical histories and neurological findings,
      gross and microscopic pathological features, and DNA analysis of the SOD1 gene.
      RESULTS: The 2 families with ALS showed a novel missense mutation in the SOD1
      gene, which was heterozygous for point mutation TTG to TCG, causing substitution
      of leucine for serine at codon 126 (Leu126Ser) in exon 5. Clinically, patients
      showed slower disease progression and lack of upper motor neuron signs.
      Neuropathologically, the autopsied patient showed the form of familial ALS with
      posterior column involvement, and the pontocerebellar tract and the dentate
      nuclei of the cerebellum were also involved. Furthermore, abundant Lewy body-like
      hyaline inclusions were observed in the affected motor and nonmotor neurons.
      CONCLUSIONS: Familial ALS with a novel Leu126Ser mutation in the SOD1 gene showed
      mild clinical features and lack of upper motor neuron signs. We believe that
      Leu126Ser might be associated with the clinical features and that the mutation
      site in the SOD1 gene and disease duration might be associated with the formation
      of Lewy body-like hyaline inclusions.

PMID- 11346369
TI  - Fluid-attenuated inversion recovery magnetic resonance imaging detects cortical
      and juxtacortical multiple sclerosis lesions.
AB  - BACKGROUND: Autopsy studies showed cortical and juxtacortical multiple sclerosis
      (MS) plaques. Fluid-attenuated inversion recovery (FLAIR) is an advanced magnetic
      resonance imaging sequence that reveals tissue T2 prolongation with cerebrospinal
      fluid suppression, allowing detection of superficial brain lesions. OBJECTIVES:
      To assess FLAIR, T1-weighted, and T2-weighted images for detecting lesions in or
      near the cerebral cortex in patients with MS and to explore the relation between
      cortical lesions and cortical atrophy. DESIGN, SETTING, AND PATIENTS: Cross
      sectional study in a university MS clinic of 84 patients with MS and 66 age
      matched healthy controls receiving 1.5-T fast FLAIR, T2-weighted, and T1-weighted
      images. MAIN OUTCOME MEASURES: Regional cortical atrophy was rated vs controls.
      Cortical and juxtacortical lesions were ovoid hyperintensities involving the
      cortex and/or gray-white junction. RESULTS: A total of 810 cortical and
      juxtacortical lesions were seen by FLAIR in patients (mean, 9.6 per patient),
      most commonly in the superior frontal lobe. Cortical and juxtacortical lesions
      were identified in 72 patients and 6 controls. Fourteen percent of cortical and
      juxtacortical lesions were seen on T1-weighted images and 26% were seen on T2
      weighted images. More cortical and juxtacortical lesions were present in
      secondary progressive disease than relapsing-remitting disease. The total number
      of cortical and juxtacortical lesions correlated significantly with disease
      duration and the regional number correlated with the degree of regional atrophy.
      After taking into account noncortical (white matter) lesions, only the cortical
      and juxtacortical lesion count predicted atrophy in that region. CONCLUSIONS:
      FLAIR can detect many cortical and juxtacortical lesions in MS, which were
      appreciated previously in autopsy studies but usually missed by magnetic
      resonance imaging during life. Cortical and juxtacortical plaque formation may
      contribute to cortical atrophy in MS.

PMID- 11346370
TI  - Neurologic and psychiatric manifestations in a family with a mutation in exon 2
      of the guanosine triphosphate-cyclohydrolase gene.
AB  - OBJECTIVE: To investigate the range of clinical features to correlate genotypic
      and phenotypic manifestations in hereditary progressive and/or levodopa
      responsive dystonia due to a defect in the guanosine triphosphate-cyclohydrolase
      (GCH1) gene. DESIGN AND SETTING: A large family from Texas was studied in an
      ambulatory setting by clinicians in genetics, neurology, and psychiatry using
      structured interviews and examinations. PATIENTS: The family was selected after
      neurometabolic investigations of a young boy (proband) with foot dystonia and
      fatigue and his father, who had a long history of anxiety and depression. Results
      of metabolic studies showed decreased levels of metabolites of biopterin and
      biogenic amines in cerebrospinal fluid. Subsequently, a novel mutation (37-base
      pair deletion) in exon 2 of the GCH1 gene was demonstrated in 11 family members.
      There was no observed female sex bias, but there was a wide variability of motor
      dysfunctions in family members. Approximately 50% had clinical deafness and a
      similar number had significant psychiatric dysfunction, including depression and
      anxiety. CONCLUSION: Study of additional families with hereditary progressive
      and/or levodopa-responsive dystonia using modern molecular methods will be
      necessary to confirm the neuropsychiatric spectrum of this disorder, in which
      important clinical features may be unrecognized and thus inappropriately managed.

PMID- 11346372
TI  - Ictal fear in temporal lobe epilepsy: surgical outcome and focal hippocampal
      changes revealed by proton magnetic resonance spectroscopy imaging.
AB  - BACKGROUND: Ictal fear (IF) is most frequently associated with epileptic
      discharges from mesial temporal areas. OBJECTIVES: To determine whether patients
      with IF were more likely to become seizure free after anteromesial temporal lobe
      resection compared with those without IF and whether they show more anteriorly
      pronounced metabolic changes assessed by means of multivoxel magnetic resonance
      spectroscopy (MRS) along the hippocampal axis. METHODS: Surgical outcome was
      assessed in 33 consecutive patients with temporal lobe epilepsy after a mean
      follow-up of 25 months (range, 12-38 months). Proton multivoxel MRS of the
      hippocampal formation was applied to detect regional differences along the axis
      of the hippocampus in patients with and without IF. Magnetic resonance tomography
      showed typical features of hippocampal sclerosis in all patients. RESULTS: Twelve
      (36%) of the 33 patients reported fear at the beginning of their habitual
      seizures. Eleven of these patients were seizure free postoperatively. In
      contrast, only 11 of 21 patients without IF had a favorable outcome. Results of
      MRS revealed significantly higher pathologic N-acetylaspartate-choline ratios in
      the anterior portion of the hippocampal formation in patients with than in those
      without IF, indicating focal metabolic and/or morphologic changes in the head of
      the hippocampus. CONCLUSIONS: These results indicate the importance of diagnosing
      auras with IF to provide a more detailed prognosis of the surgical outcome. In
      addition, our data emphasize that multivoxel MRS is a valuable tool in the
      presurgical evaluation, as it may reveal different topographical patterns of
      hippocampal sclerosis.

PMID- 11346371
TI  - Improvement in chronic ischemic neuropathy after intramuscular phVEGF165 gene
      transfer in patients with critical limb ischemia.
AB  - OBJECTIVE: To investigate the effects of vascular endothelial growth factor gene
      therapy on ischemic neuropathy in patients with critical limb ischemia. DESIGN:
      An open-label, dose-escalating trial. Patients with angiographically proven
      critical leg ischemia received injections of phVEGF(165) human plasmid in the
      muscles of the ischemic limb. Testing before treatment and at 3 and 6 months
      included (1) symptom severity score, (2) clinical examination score, and (3)
      electrophysiologic studies. Clinical and electrophysiologic examiners were masked
      to each other's findings. SETTING: A tertiary care referral hospital and a major
      teaching affiliate of Tufts University School of Medicine, Boston, Mass. RESULTS:
      Of 29 consecutive patients enrolled, 17 (19 limbs) completed the 6 months of
      study. Six patients had diabetes. Compared with baseline studies, treated
      patients had significant clinical improvements in the symptom score (P<.01),
      sensory examination score (P<.01), total examination score (P =.01), peroneal
      motor amplitude (P =.03), and quantitative vibration threshold (P =.04).
      Improvement in the vascular ankle-brachial index in treated legs (P<.01)
      corresponded to improvement in neuropathy in the same limb. Neurologic
      improvement was seen in 4 of 6 patients with diabetes who completed the study. No
      clinical, electrophysiologic, or vascular improvements were observed in untreated
      legs. CONCLUSIONS: Ischemic neuropathy might be a reversible condition, and
      therapeutic angiogenesis might be an effective treatment. The presence of
      diabetes does not preclude a response to this therapy.

PMID- 11346373
TI  - Long-term efficacy and safety of piracetam in the treatment of progressive
      myoclonus epilepsy.
AB  - BACKGROUND: Piracetam has been proven to be effective and well tolerated in the
      treatment of myoclonus in short-term studies. OBJECTIVE: To assess its long-term
      clinical efficacy, 11 patients with disabling myoclonus due to progressive
      myoclonus epilepsy were treated with piracetam in an open-label study. METHODS:
      Neurologic outcome (at the 1st, 6th, 12th, and 18th month of treatment) was
      assessed by an adjusted sum score of the following 3 indices: motor impairment,
      functional disability, and global assessment of disability due to myoclonus.
      Severity of other neurologic symptoms (seizure frequency and severity,
      dysarthria, and gait ataxia) also was assessed. Treatment with piracetam was
      initiated at a dose of 3.2 g/d that was gradually increased until stable benefit
      was noted (maximal dose in the trial was 20 g/d). Concomitant antiepileptic drugs
      were maintained at their previous dose. RESULTS: Statistically significant
      improvement in the total rating score was observed after introduction of
      piracetam at the 1st, 6th, and 12th month of treatment. Severity of other
      neurologic symptom scores did not improve significantly. Two patients reported
      drowsiness during the first 2 weeks of treatment. CONCLUSIONS: Piracetam given as
      add-on therapy seems to be an effective, sustained, and well-tolerated treatment
      of myoclonus. In patients with progressive myoclonus epilepsy, the efficacy of
      the drug increased during the first 12 months of treatment and then stabilized.

PMID- 11346374
TI  - Spinocerebellar ataxia type 1 in China: molecular analysis and genotype-phenotype
      correlation in 5 families.
AB  - BACKGROUND: Twelve genetic types of autosomal dominant hereditary ataxia have
      been recently identified and the genes responsible for most of them cloned.
      Molecular identification of the type of ataxia is important to determine the
      disease prevalence and its natural history in various populations. OBJECTIVES: To
      perform molecular analysis of 75 Chinese families affected with spinocerebellar
      ataxia (SCA) and to evaluate the spectrum of mutations in these genes and the
      correlation between genotypes and phenotypes in Chinese patients. SETTING:
      Neurogenetics Unit, China-Japan Friendship Hospital, Beijing, China. METHODS: One
      hundred nine patients from 75 kindreds diagnosed as having autosomal dominant
      SCA, 16 patients with sporadic SCA or spastic paraplegia, 280 control chromosomes
      of the Chinese population, and 120 control chromosomes of the Sakha population
      were selected for this study. We conducted detailed mutational analysis by direct
      sequencing of polymerase chain reaction products amplified from genomic DNA.
      RESULTS: Spinocerebellar ataxia type 1 (SCA1) was identified in 5 families with
      12 studied patients. All affected family members were heterozygous for a CAG
      repeat expansion in the SCA1 gene containing 51 to 64 trinucleotide repeats.
      Normal alleles had 26 to 35 repeats. Spinocerebellar ataxia type 1 accounted for
      7% of the studied Chinese families with ataxia. In addition, we determined the
      frequency of a single vs double CAT interruption in 120 control chromosomes of
      the Siberian Sakha population, which has the highest known prevalence of SCA1,
      and compared this with 280 control chromosomes from the Chinese populations. The
      results show that 64.7% of the Siberian normal alleles contain a single CAT
      interruption, whereas 92% of the Chinese had more than 1 interruption.
      CONCLUSIONS: Spinocerebellar ataxia type 1 is responsible for 7% of affected
      families in the Chinese population. A correlation between the prevalence of SCA1
      and the number of CAT interruptions in the trinucleotide chain suggests that a
      CAT-to-CAG substitution may have been the initial event contributing to the
      generation of expanded alleles and influencing relative prevalence of SCA1.

PMID- 11346375
TI  - Recurrence of acute disseminated encephalomyelitis at the previously affected
      brain site.
AB  - BACKGROUND: Acute disseminated encephalomyelitis (ADEM) is a usually monophasic
      demyelinating disorder of the central nervous system. Recurrences pose a
      diagnostic challenge because they can be overlooked or suggest an alternative
      diagnosis. OBJECTIVE: To examine the frequency, nature, and outcome of recurrent
      ADEM. DESIGN: Review of the medical records of patients diagnosed in our
      institution as having ADEM between January 1, 1983, and May 31, 1998. Recurrences
      were defined as appearance of new symptoms and signs at least 1 month after the
      previous episode. RESULTS: Five (24%) of 21 patients with ADEM developed
      recurrent disease episodes. In all, diagnosis was confirmed by brain biopsy. One
      patient had 4 disease episodes, 2 had 3, and the other 2 each had 2. Recurrence
      appeared 1.5 to 32 months after initial presentation and involved the same brain
      territory in 6 of 9 recurrences in 3 of 5 patients. In 2 patients, recurrences
      included neuropsychiatric signs. A good response to corticosteroid therapy was
      observed in 10 of 13 of treated ADEM attacks: in 3 of the 4 treated initial
      events and in 7 of 9 recurrences. CONCLUSIONS: Recurrent ADEM may be more
      prevalent than previously recognized. Patients who relapse tend to have more than
      1 recurrence that usually involves, clinically and radiologically, a brain
      territory that was affected before and can simulate a space-occupying lesion that
      requires histologic diagnosis. Neuropsychiatric features may be the main
      presentation of a relapse. Since recurrent ADEM is a corticosteroid-responsive
      condition, awareness and early diagnosis are mandatory.

PMID- 11346376
TI  - Acute severe spinal cord dysfunction in bacterial meningitis in adults: MRI
      findings suggest extensive myelitis.
AB  - BACKGROUND: Bacterial meningitis is rarely complicated by acute spinal cord
      involvement (eg, myelitis, ischemic infarction, spinal abscess, or epidural
      hemorrhage). In spinal cord dysfunction, magnetic resonance imaging (MRI) is the
      imaging modality of choice. Still, MRI findings of myelitis due to bacterial
      meningitis in adults have not been reported. METHODS: Spinal MRIs were obtained
      during the acute stage of meningitis and on follow-up in 3 adults with bacterial
      meningitis that was complicated by paraparesis or tetraparesis and bowel and
      bladder incontinence. The causative pathogens were Streptococcus pneumoniae and
      Neisseria meningitidis; in 1 patient, the pathogen was not identified. RESULTS:
      In all cases, spinal MRI ruled out a compression of the cord by an extramedullary
      mass but demonstrated hyperintensities on T2-weighted images that predominantly
      involved the gray matter and extended from the cervical to the lumbar cord.
      Leptomeningeal and discrete nodular intramedullary enhancement on T1-weighted
      images was detected only in 1 patient. Follow-up examinations revealed that
      hyperintensities resolved completely in 1 patient, while a central cavitation
      developed in the cervical spinal cord of another, and the MRI findings were
      progressive during the first 4 weeks in the third patient. In all cases, severe
      paresis and bowel and bladder incontinence persisted. CONCLUSION: We demonstrate
      for the first time the MRI findings of adults with acute spinal cord involvement
      during bacterial meningitis. Magnetic resonance imaging showed central
      intramedullary hyperintensities on T2-weighted images that extended from the
      cervical to the lumbar cord, indicating myelitis. Clinical follow-up examinations
      suggest that myelitis during bacterial meningitis has an unfavorable prognosis.

PMID- 11346377
TI  - Medium-chain acyl coenzyme A dehydrogenase deficiency: occurrence in an infant
      and his father.
AB  - BACKGROUND: Autosomal recessive inborn errors of metabolism often present as life
      threatening disease in infancy and have adverse effects on the nervous system.
      Parents are usually heterozygotes. This is true of most disorders of fatty acid
      oxidation, which are rare and present with hypoketotic hypoglycemia. However, the
      gene for medium-chain acyl coenzyme A dehydrogenase (MCAD) deficiency is common
      in white people, raising the possibility that a parent may be homozygous.
      OBJECTIVE: To document the occurrence of MCAD deficiency in a 12-month-old boy
      and his father, both of whom were homozygous for the A985G mutation. DESIGN:
      Clinical observations and definitive biochemical testing. SETTING: Children's
      hospital and university laboratory. PARTICIPANTS: One child and one adult.
      INTERVENTIONS: Diagnosis and treatment. MAIN OUTCOME MEASURES: Clinical outcome;
      analysis results of plasma and urine for carnitine and organic acids. RESULTS: An
      infant admitted with an acute illness requiring intensive care was found to have
      carnitine deficiency and dicarboxylic aciduria; MCAD deficiency was diagnosed by
      assay of his DNA for the common mutation. Test results of the father revealed him
      also to be homozygous. CONCLUSION: In MCAD deficiency, as opposed to the usual
      rare autosomal recessive metabolic disease, a parent may also be an affected
      homozygote.

PMID- 11346378
TI  - Treatment of myelopathy in Sjogren syndrome with a combination of prednisone and
      cyclophosphamide.
AB  - BACKGROUND: Peripheral neuropathy is a common complication of primary Sjogren
      syndrome, but central nervous system involvement also occurs and may be the only
      extraglandular manifestation. Sicca symptoms may also be minimal. Combinations of
      lesions along with relapses and remissions can suggest multiple sclerosis in the
      proper clinical setting, making the correct diagnosis elusive. OBJECTIVES: To
      report a case of progressive transverse myelopathy with previous optic neuropathy
      in primary central nervous system Sjogren syndrome (CNS-SS), and to review 17
      previously reported cases and the patient's responses to various therapies.
      DESIGN: Case report and literature review. SETTING: University hospital. PATIENT:
      A 63-year-old Hispanic woman with a 10-month history of progressive spastic
      paraparesis associated with optic neuropathy and a T10 sensory level. Magnetic
      resonance imaging demonstrated multifocal, contrast-enhancing lesions in the
      spinal cord. The patient was diagnosed as having CNS-SS because of the presence
      of sicca symptoms, abnormal serological test results, and salivary gland biopsy
      results, which fulfilled San Diego criteria for "definite" Sjogren syndrome. She
      responded to treatment with a combination of prednisone and cyclophosphamide.
      CONCLUSIONS: Diagnosis of primary CNS-SS requires a high index of suspicion and
      specialized clinical testing. Treatment with pulse doses of corticosteroids alone
      may be suboptimal, but results of treatment with a combination of corticosteroids
      and either cyclophosphamide or chlorambucil have been encouraging.

PMID- 11346379
TI  - Dermal sinus presenting as group B streptococcal meningitis.

PMID- 11346380
TI  - Amyloid neuropathy: a peculiar form of peripheral neuropathy.

PMID- 11346381
TI  - Neurology was there-1980.

PMID- 11346382
TI  - Premorbid brain volume and dementia.

PMID- 11346384
TI  - The use and abuse of correlation coefficients.

PMID- 11346385
TI  - Surrogate markers in multiple sclerosis.

PMID- 11346387
TI  - Acute orthostatic hypotension when starting dopamine agonist therapy in parkinson
      disease: the role of domperidone therapy.

PMID- 11346389
TI  - CT perfusion: two publications, same patients, different results.

PMID- 11346391
TI  - Diabetes and postoperative endophthalmitis in the endophthalmitis vitrectomy
      study.
AB  - OBJECTIVES: To determine whether there was a different response to vitrectomy and
      tap/biopsy with or without systemic antibiotic treatment in the Endophthalmitis
      Vitrectomy Study and whether the signs and symptoms of endophthalmitis differ
      between diabetic and nondiabetic patients. DESIGN: A multicenter clinical trial
      in which patients with acute post-cataract extraction endophthalmitis were
      randomly assigned in a 2 x 2 factorial design to vitrectomy or tap/biopsy, in
      each case with or without intravenous antibiotics, and followed up for 9 months.
      Outcome measures included visual acuity assessed in standardized fashion.
      RESULTS: Fifty-eight of 420 study patients had diabetes. Diabetic patients had
      slightly worse vision and ocular media at the baseline assessment. Only 39% of
      diabetic patients compared with 55% of nondiabetic patients achieved 20/40 final
      vision. Both diabetic and nondiabetic patients with initial light perception (LP)
      only vision had better visual results with immediate vitrectomy. For those with
      better than LP baseline vision, patients with diabetes achieved visual acuity of
      20/40 more often with vitrectomy (57%) than with tap/biopsy (40%), but this
      difference was not statistically significant. Patients without diabetes did
      equally well with vitrectomy or tap/biopsy. CONCLUSIONS: For patients with better
      than LP vision, tap/biopsy is appropriate for those without diabetes. A clinical
      trial of a sufficient number of diabetic patients with better than LP vision is
      necessary to determine the best management for this group. At present, initial
      vitrectomy or tap/biopsy are reasonable approaches for diabetic patients with
      better than LP vision.

PMID- 11346392
TI  - Amniotic membrane inlay and overlay grafting for corneal epithelial defects and
      stromal ulcers.
AB  - OBJECTIVES: To determine the effect of amniotic membrane transplantation (AMT) on
      persistent corneal epithelial defects (PEDs) and to compare the efficacy between
      inlay and overlay techniques. METHODS: Thirty patients (30 eyes) underwent AMT
      for PED. The use of AMT was restricted to patients in whom all previous measures,
      including bandage contact lens and tarsorrhaphy, had failed. The amniotic
      membrane was placed on the surface of the cornea in overlay (group A) or inlay
      (group B) fashion. RESULTS: The PED healed after the first AMT in 21 eyes (70%)
      within an average of 25.5 days after surgery and recurred in 6 eyes (29%). Among
      the 22 eyes treated with an overlay AMT (group A), the PED healed after the first
      AMT in 14 eyes (64%) within an average of 24.5 days and recurred in 4 eyes (29%).
      Among the 8 eyes treated with an inlay AMT (group B), the PED healed within an
      average of 27.4 days after AMT, which did not statistically significantly differ
      from group A (P = .72). The PED healed after the first AMT in 7 eyes (88%) and
      recurred in 2 (29%) of 7 eyes. CONCLUSIONS: The AMT can be helpful in the
      treatment of PED in which all other conventional management has failed. However,
      the success rate in our study was not as high as that previously reported, and
      our results showed a high incidence of recurrences of epithelial defects. We did
      not find any difference between overlay and inlay techniques in terms of healing
      time and recurrence rate.

PMID- 11346393
TI  - Assessment of visual function in patients with gyrate atrophy who are considered
      candidates for gene replacement.
AB  - OBJECTIVE: To assess the course of change of visual function outcome variables in
      5 patients with gyrate atrophy before a gene replacement therapy clinical trial.
      METHODS: The outcome variables selected were visual field sensitivity and
      electroretinogram amplitude. The course of change of these outcome variables was
      determined by calculation of their half-lives. RESULTS: In the 4 to 6 years
      during which each patient was followed up for this study, median visual field
      half-lives were 17.0 years (static perimetry) and 11.4 years (kinetic perimetry).
      Median electroretinogram half-lives were 16.0 years (maximal response) and 10.7
      years (flicker response). CONCLUSIONS: The course of the decline of visual
      function outcome variables is frequently slow. Thus, a long-term clinical trial
      would be required to assess the efficacy of the intervention in the preservation
      of visual function.

PMID- 11346395
TI  - High injection pressure during intralesional injection of corticosteroids into
      capillary hemangiomas.
AB  - BACKGROUND: Intralesional injection of corticosteroids is an effective treatment
      for tumors of the head and neck. Complications are rare but include permanent
      loss of vision. We designed a study to investigate the mechanism for this
      complication. METHODS: Three fellowship-trained pediatric ophthalmologists
      participated in the study in a nonmasked fashion. Four patients received 5
      separate treatment sessions of an intralesional injection of a 50-50 mixture of
      triamcinolone diacetate (40 mg/mL) and betamethasone sodium phosphate and
      betamethasone acetate (6 mg/mL) into capillary hemangiomas. Injection pressure
      was obtained in real time using a cannula designed for this purpose. Maximum
      pressure, mean pressure, and volume of corticosteroid were measured from each
      injection. RESULTS: A total of 71 injections (range, 8-33 injections per patient)
      was performed. The total volume of corticosteroid ranged from 0.9 to 2.1 mL. In
      63 of 71 injections, the maximum pressure exceeded 100 mm Hg (range, 18.65-842.18
      mm Hg). Each surgeon produced injection pressures greater than the systemic
      arterial pressures of each patient. CONCLUSIONS: Injection pressures exceeding
      the systemic arterial pressures routinely occur during intralesional injections
      of corticosteroids into capillary hemangiomas. Experienced surgeons participating
      in a nonmasked protocol were unable to prevent high injection pressures of
      corticosteroid. A sufficient volume of corticosteroid injected at high injection
      pressure would account for the embolization of corticosteroid particles into the
      ocular circulation from retrograde arterial flow. We recommend limiting the
      volume of corticosteroid and performing indirect ophthalmoscopy on all patients
      receiving injections of long-acting corticosteroids into the orbit and
      periorbital soft tissue.

PMID- 11346394
TI  - Assessment of metastatic disease status at death in 435 patients with large
      choroidal melanoma in the Collaborative Ocular Melanoma Study (COMS): COMS report
      no. 15.
AB  - BACKGROUND: A systematic review and assessment of disease-related mortality as
      part of standardized prospective patient follow-up and evaluation within a
      multicenter clinical trial have been lacking in previous studies of choroidal
      melanoma. OBJECTIVE: To describe disease status at death in patients with large
      choroidal melanoma treated and followed up in the Collaborative Ocular Melanoma
      Study (COMS). DESIGN: Analysis of reviews of patient status at death performed by
      the COMS Mortality Coding Committee using available clinical and histopathologic
      information. SETTING AND PATIENTS: Reviews of deaths as of July 31, 1997, the
      cutoff date for reporting initial mortality findings. INTERVENTIONS: Patients
      were treated by either enucleation preceded by external beam radiotherapy or
      enucleation only. MAIN OUTCOME MEASURES: Disease status at the time of death and
      certainty associated with the coding of disease status, sites of metastasis, and
      availability of autopsy. RESULTS: Of 1003 patients enrolled in the trial, 457 had
      died; the estimated median survival from time of enrollment was 7.4 years.
      Disease status at time of death had been reviewed for 435 deaths (95%). The
      autopsy rate was 6%. A total of 269 patients (62%) had histopathologically
      confirmed melanoma metastasis at the time of death, and metastasis was suspected
      in 92 additional patients (21%) on the basis of imaging and tests but without
      tissue confirmation. The common sites were liver (93%), lung (24%), and bone
      (16%); multiple sites were identified in 87% of patients with metastasis. The
      likelihood of 3 or more sites increased more than 4-fold when autopsy results
      were available. CONCLUSIONS: Detailed mortality coding following a standard
      protocol provides the most accurate reporting to date of disease-related
      mortality in patients with choroidal melanoma and also identifies difficulties.
      Guidelines for the evaluation of future patients in clinical studies of choroidal
      melanoma are suggested.

PMID- 11346396
TI  - Comparison of materials used in frontalis suspension.
AB  - OBJECTIVE: To compare various materials used in frontalis suspension surgery for
      incidence of infection and/or granuloma formation and incidence of recurrent
      ptosis. DESIGN AND METHODS: A retrospective medical record analysis was performed
      for 102 frontalis suspension operations performed on 43 patients between January
      1, 1991, and December 31, 1996, at Indiana University Medical Center,
      Indianapolis. Materials used for surgery were compared for incidence of infection
      and/or granuloma formation and incidence of recurrent ptosis. Materials included
      autogenous fascia lata, banked fascia lata, monofilament nylon, braided
      polyester, expanded polytetrafluoroethylene, and polypropylene. RESULTS:
      Infection and/or granuloma formation occurred in 10.8% of all frontalis
      suspensions and in less than 10.0% for each material used except expanded
      polytetrafluoroethylene. Five (45.5%) of the 11 frontalis suspensions using
      expanded polytetrafluoroethylene required removal of the material because of
      suspected infection. Ptosis recurred in 32 cases (31.4%). Low incidence of
      recurrence was found with autogenous fascia lata and expanded
      polytetrafluoroethylene. CONCLUSIONS: Of the materials compared in this study,
      autogenous fascia lata may be the material of choice for frontalis suspension
      surgery in congenital ptosis. Other materials are useful for temporary eyelid
      elevation. All materials carry the risk of potential infection and/or granuloma
      formation.

PMID- 11346397
TI  - Pterygia pathogenesis: corneal invasion by matrix metalloproteinase expressing
      altered limbal epithelial basal cells.
AB  - OBJECTIVE: To assess the potential role of matrix metalloproteinases (MMPs) in
      the pathogenesis of pterygia by comparing the immunolocalization patterns of MMPs
      in altered limbal basal stem cells, activated fibroblasts, and areas of elastotic
      degeneration adjacent to the pterygia. METHODS: Nine primary and 1 recurrent
      pterygia along with normal superior limbal-conjunctival tissue and cornea were
      immunostained with mouse monoclonal antibodies specific for MMP-1, MMP-2, MMP-3,
      MMP-9, membrane type 1 (MT1)-MMP (MMP-14), and membrane type 2-MMP (MMP-15).
      RESULTS: Normal conjunctival, limbal, and corneal cells lacked significant
      immunostaining except for cell surface MT1-MMP. In contrast, altered limbal basal
      epithelial cells of the 9 primary and 1 recurrent pterygia immunostained for all
      6 MMPs. Activated and altered fibroblasts associated with the pterygia
      immunostained primarily for MMP-1. In contrast, stromal areas of elastotic
      degeneration (pingueculae) showed variable immunostaining of MMPs. CONCLUSIONS:
      Altered limbal basal epithelial cells (pterygium cells) immunostained for
      multiple types of MMPs in contrast to normal conjunctival, limbal, and corneal
      cells. The pterygium cells invading over Bowman's layer produce elevated MMP-1,
      MMP-2, and MMP-9 expression, which probably are the main MMPs responsible for the
      dissolution of Bowman's layer. Pterygium cells may also cause activation of
      fibroblasts at the head of the pterygium, leading to the initial cleavage of
      fibrillar collagen in Bowman's layer by the production of MMP-1. Altered
      fibroblasts in areas of elastotic degeneration (pingueculae) trailing behind the
      pterygium constitute a second type of tumor, which is noninvasive. CLINICAL
      RELEVANCE: These data of altered MMP expression support the concept that altered
      basal limbal epithelial cells play a key role in the formation and migration of a
      pterygium.

PMID- 11346398
TI  - Response of experimental retinal neovascularization to thiazolidinediones.
AB  - OBJECTIVE: To determine the effect of thiazolidinediones (TZDs) on experimental
      retinal neovascularization. METHODS: The ability of the TZDs troglitazone and
      rosiglitazone maleate (1-20 micromol/L) to inhibit retinal endothelial cell (REC)
      proliferation, migration, tube formation, and signaling was determined in
      response to vascular endothelial growth factor (VEGF). In vivo studies were
      performed using the oxygen-induced ischemia model of retinal neovascularization.
      Neonatal mice were treated with intravitreous injection of 0.5 microL of
      troglitazone (100 micromol/L) or rosiglitazone maleate (100 micromol/L), or
      vehicle, and retinal neovascularization was assayed qualitatively and
      quantitatively by means of angiography and histological examination. RESULTS:
      Expression of the TZD receptor, peroxisome proliferator-activated receptor gamma,
      was confirmed in RECs by means of Western immunoblotting. Rosiglitazone and
      troglitazone inhibited VEGF-induced migration (P< .05), proliferation (P< .05),
      and tube formation (P< .01) by RECs in vitro beginning at 10 micromol/L.
      Rosiglitazone and troglitazone inhibited phosphorylation of extracellular signal
      regulated mitogen-activated protein kinase 1 in RECs. Intravitreous injection of
      rosiglitazone or troglitazone inhibited development of retinal neovascularization
      (P< .01) but did not significantly inhibit VEGF overexpression in the ganglion
      cell layer of the ischemic retina. CONCLUSION: The TZDs inhibit experimental
      retinal neovascularization with an effect that is primarily downstream of VEGF
      expression. CLINICAL RELEVANCE: The TZDs are widely prescribed and should be
      evaluated for their potential to inhibit the progression of diabetic retinopathy.

PMID- 11346399
TI  - Eye banking and screening for Creutzfeldt-Jakob disease.
AB  - OBJECTIVES: To quantify the risk of Creutzfeldt-Jakob disease (CJD) among cornea
      donors, evaluate supplemental screening strategies, and address concerns about
      the adequacy of current methods of screening tissue donors in the United States.
      METHODS: Reported data on deaths due to CJD and from all causes were used to
      estimate the rate of CJD among cornea donors. The impact of increased screening
      on risk of CJD and donor supply was evaluated. RESULTS: Only 1.3 of the
      approximately 45 000 cornea donors in the United States each year might be
      expected to have CJD. Most of the estimated risk (91%) is due to preclinical
      (asymptomatic) disease and therefore could not be eliminated by screening for
      signs or symptoms. If only the highest-risk age group (60 to 69 years) were
      screened and specificity were 90%, more than 21 000 otherwise acceptable donors
      would incorrectly be excluded over a period of 17.5 years to correctly exclude a
      single donor with symptomatic CJD. CONCLUSIONS: Currently, the risk of CJD
      transmission following cornea transplantation is remarkably low. Screening for
      symptoms of CJD would have minimal impact on safety, but would reduce donor
      supply and likely result in many patients not receiving needed treatment.

PMID- 11346400
TI  - Cataract extraction rates among Chinese, Malays, and Indians in Singapore: a
      population-based analysis.
AB  - OBJECTIVE: To describe the rates of cataract extraction among Chinese, Malays,
      and Indians in an urban population in Asia. DESIGN: Population-based incidence
      study using data from a medical savings fund. STUDY POPULATION: Chinese, Malay,
      and Indian residents in Singapore. METHODS: Data on all cataract operations
      performed for "senile cataract" (International Classification of Diseases, Ninth
      Revision, Clinical Modification code 366.1) between 1991 and 1996 were retrieved
      from Medisave, a population-wide, government-administered medical savings fund.
      The Singapore census was used as a denominator to allow an estimation of age,
      sex, and race-specific annual rates of cataract surgery. RESULTS: Between 1991
      and 1996, 61 210 cataract operations for "senile cataract" were performed on
      Singapore residents, which is equivalent to an average rate of 356.4 cataract
      operations per 100 000 persons per year (95% confidence interval [CI], 353.6
      359.2). The average rate was highest for Indians (age-sex adjusted rate of 396.5
      per 100 000/year), followed by Chinese (371.2 per 100 000/year), and lowest for
      Malays (237.2 per 100 000/year). Women had higher rates of cataract extraction
      than men (age-adjusted relative risk, 1.14; 95% CI, 1.11-1.17), with this pattern
      consistent across the 3 racial groups. The rate of cataract extraction increased
      by an average of 40 operations per 100 000/year (95% CI, 28.6-52.8) between 1991
      and 1996. Overall, the proportion of cataract extraction without concurrent
      intraocular lens implantation was low (n = 762, 1.2%), but rates still decreased
      by an average of 0.8 per 100 000 per year (95% CI, 0.03-1.5) during the 6 years.
      CONCLUSIONS: The rate of cataract extraction in Singapore is consistent with
      rates seen in developed countries in the West. Racial variation in rates suggests
      varying predisposition to cataract development and/or threshold for cataract
      surgery between Chinese, Malay, and Indian populations in Singapore.

PMID- 11346401
TI  - The NEI-VFQ-25 in people with long-term type 1 diabetes mellitus: the Wisconsin
      Epidemiologic Study of Diabetic Retinopathy.
AB  - OBJECTIVES: To examine the association of the 25-item National Eye Institute
      Visual Function Questionnaire (NEI-VFQ-25) overall and specific scale scores with
      visual acuity, diabetic retinopathy, and other characteristics, in a cohort of
      persons with type 1 diabetes. DESIGN: Population-based cohort study. SETTING: An
      11-county area in southern Wisconsin. PARTICIPANTS: Six hundred two persons with
      diabetes whose conditions were diagnosed when they were younger than 30 years and
      who were currently taking insulin participated in baseline, 4-year, 10-year, and
      14-year follow-up examinations. MAIN OUTCOME MEASURES: An interview that
      consisted of the 25-item NEI-VFQ was completed. Visual acuity was measured by the
      Early Treatment of Diabetic Retinopathy Study (ETDRS) protocol and the presence
      and severity of retinopathy and macular edema were detected by masked grading of
      stereoscopic color fundus photographs using the modified Airlie House
      classification and the ETDRS retinopathy severity scheme. RESULTS: Univariate
      analyses revealed that the total NEI-VFQ-25 score was lower in persons who were
      older, had a longer duration of diabetes, higher glycosylated hemoglobin, were in
      renal failure, had a history of cardiovascular disease, hypertension, or
      amputation of a lower limb, had poorer visual acuity, more severe diabetic
      retinopathy, macular edema, glaucoma, cataract, abnormalities in tactile
      sensation or temperature sensitivity, smoked more total pack-years, led a more
      sedentary lifestyle, and had poor peak expiratory flow. In multivariate analyses,
      while controlling for the physical and mental component scores from the Medical
      Outcomes Survey 36-Item Short-Form Health Survey as measures of comorbidity,
      lower total NEI-VFQ-25 scores were independently associated with poorer visual
      acuity, more severe retinopathy, older age, history of loss of tactile sensation,
      and more total pack-years of cigarettes smoked. CONCLUSIONS: In this cross
      sectional study, the 25-item NEI-VFQ seems to be strongly associated with vision,
      independent of severity of retinopathy and other complications associated with
      type 1 diabetes. It may be a useful measure of health-related quality of life as
      it relates to vision in epidemiological studies and clinical trials in persons
      with diabetes.

PMID- 11346402
TI  - Variation of codons 1961 and 2177 of the Stargardt disease gene is not associated
      with age-related macular degeneration.
AB  - OBJECTIVES: To investigate the role of 2 specific alleles of the Stargardt
      disease gene (ABCA4) in the pathogenesis of age-related macular degeneration
      (AMD). Secondary objectives were to investigate differences in frequency of the
      G1961E allele in selected ethnic groups as well as to examine the segregation of
      both G1961E and D2177N alleles in 5 multiplex families with AMD. METHODS: Five
      hundred forty-four patients with AMD and 689 controls were ascertained from 3
      continents. Blood samples from 62 normal individuals of Somalian ancestry were
      also obtained. Participants were screened for the presence of these ABCA4 alleles
      with a combination of restriction digestion and single-strand conformation
      polymorphism analysis of polymerase chain reaction amplification products.
      Detected alleles were confirmed by DNA sequencing. The number of subjects
      exhibiting the G1961E or D2177N variants were compared between AMD and control
      groups using a 2-tailed Fisher exact test. RESULTS: There was no significant
      difference (P >.1) in the frequency of the G1961E and D2177N alleles in patients
      with AMD (2.2%) vs controls (1.0%). In contrast, there was a significant
      difference (P< .001) in the frequency of the G1961E alleles between normal
      individuals of Somali ancestry (11.3%) and normal individuals from other
      populations (0.4%). There was no evidence of cosegregation of these alleles and
      the AMD phenotype in the 5 multiplex families with AMD examined. These two ABCA4
      alleles were slightly more frequent in patients with AMD with choroidal
      neovascularization (2.7%) than those without this complication (2.5%).
      CONCLUSIONS: Somali ancestry is more than 100 times more strongly associated with
      presence of the G1961E allele than the AMD phenotype. This study did not find any
      statistically significant evidence for involvement of the G1961E or D2177N
      alleles of the ABCA4 gene in AMD. CLINICAL RELEVANCE: The ABCA4 gene is
      definitively involved in the pathogenesis of Stargardt disease and some cases of
      photoreceptor degeneration. However, it does not seem to be involved in a
      statistically significant fraction of AMD cases.

PMID- 11346403
TI  - The ABCA4 gene and age-related macular degeneration: innocence or guilt by
      association.

PMID- 11346404
TI  - Management of endophthalmitis in the post-endophthalmitis vitrectomy study era.

PMID- 11346405
TI  - Oculoplastic surgeons think mechanically.

PMID- 11346406
TI  - Understanding the value of diabetic retinopathy screening.

PMID- 11346407
TI  - One hundred important 20th-century ophthalmic books.

PMID- 11346408
TI  - Primary intraepithelial sebaceous gland carcinoma of the palpebral conjunctiva.
AB  - Sebaceous gland carcinoma usually arises from meibomian or Zeis glands deep
      within the eyelid, but it can rarely arise within the conjunctival epithelium
      without a deep component. We describe a woman with a history of chronic
      blepharoconjunctivitis unresponsive to topical medications. Examination disclosed
      confluent papillary hypertrophy of the upper palpebral conjunctiva and deposits
      of white flaky material. Tarsoconjunctival punch biopsy revealed intraepithelial
      sebaceous gland carcinoma. Management consisted of frozen section-controlled
      complete tumor excision with removal of the entire posterior lamella of the right
      upper eyelid, cryotherapy to the margins, and reconstruction. Histopathologic
      analysis confirmed primary sebaceous gland carcinoma localized to the
      conjunctival epithelium without involvement of underlying meibomian or Zeis
      glands or the caruncle. Patients with unexplained chronic unilateral
      blepharoconjunctivitis or papillary hypertrophy of the palpebral conjunctiva
      should be considered for biopsy to rule out neoplasia, even when there is no sign
      of an underlying eyelid mass.

PMID- 11346409
TI  - Posttransplantation lymphoproliferative disorder initially seen as iris mass and
      uveitis.
AB  - Primary ocular posttransplantation lymphoproliferative disorder is rare. Epstein
      Barr virus is implicated as the cause as a result of systemic immunosuppression
      after transplant surgery. We studied a patient who developed ocular
      posttransplantation lymphoproliferative disorder after orthotopic liver
      transplantation. Slitlamp and light microscopic photographs confirmed the
      diagnosis.

PMID- 11346410
TI  - Orbital intradiploic giant epidermoid cyst.
AB  - We report a case of an intradiploic epidermoid cyst of the lateral orbital wall
      that resulted in proptosis and downward displacement of the left eye. Computed
      tomography and magnetic resonance imaging revealed a bone-destroying mass
      involving the frontal, sphenoid, and zygomatic bones that extended into the
      orbit, temporalis, and anterior cranial fossa. Complete surgical removal was
      performed through a lateral orbitotomy. The lateral wall was reconstructed with a
      porous polyethylene sheet. The cyst has not recurred after 18 months of follow
      up.

PMID- 11346411
TI  - Case reports and small case series: LASIK-associated visual field loss in a
      glaucoma suspect.

PMID- 11346412
TI  - Case reports and small case series: topiramate-induced acute myopia and retinal
      striae.

PMID- 11346413
TI  - Case reports and small case series: ocular and cerebral ischemia following facial
      injection of autologous fat.

PMID- 11346414
TI  - Case reports and small case series: scleritis occurring in association with
      Takayasu disease.

PMID- 11346415
TI  - Photo essay: iris melanoma in a 6-year-old girl.

PMID- 11346416
TI  - Cataract extraction and hypotony after trabeculectomy.

PMID- 11346418
TI  - Does endophthalmitis following strabismus surgery require scleral perforation?

PMID- 11346422
TI  - Analysis of the performance characteristics of the University of Washington
      Quality of Life instrument and its modification (UW-QOL-R).
AB  - BACKGROUND: During a 5-year period, we analyzed 3 patient subsets from the
      University of Washington Quality of Life (UW-QOL) Registry and published the
      results. In each instance, editorial review has raised legitimate concerns
      regarding the UW-QOL instrument that deserve public comment. We present our
      response to these criticisms. Since our original publication (1993), we have
      added domains to the original UW-QOL instrument. These additions reflected our
      concern that we might be missing important elements in the spectrum of disease
      specific response to treatment. Using the data we have accumulated in the last 5
      years, we present an analysis of the internal consistency of the UW-QOL. We have
      identified those domains that are responsive (or not responsive) to treatment
      effect and have revised the UW-QOL accordingly to create the UW-QOL-R, which is
      recommended for future use. DESIGN: The project began January 1, 1993, after
      approval by the UW Human Subjects Committee. Critical comments offered by
      external review were collated and responded to. Internal consistency was
      evaluated by interitem correlation matrix (Cronbach alpha) testing. SUBJECTS: All
      new patients presenting to the UW Medical Center (Seattle) with a diagnosis of
      head and neck cancer were asked to participate in a prospective analysis of QOL
      changes during and after treatment. INTERVENTION: Patients completed the
      pretreatment QOL questionnaire on the day of their initial workup. The format for
      the pretreatment test was an interviewer-supervised self-administered test; the
      subsequent tests were self-administered and were completed at 3, 6, 12, 24, and
      36 months. Other data entered for each patient included site, stage, treatment,
      histologic classification, reconstruction, and current status. A QOL registrar
      was responsible for patient follow-up, data collection, and collation. All data
      were entered into the departmental relational database. RESULTS: Criticisms by
      external review included the following: "it is improper to call it [UW-QOL] a
      measure of quality of life"; "the summary scale is problematic because it implies
      that each of the subscales are weighted or 'valued' equally"; "some domain
      questions relate to surgery specific issues. while others are specific to
      radiation"; "we were confused by the scoring"; and "the UW-QOL index does not
      specifically address the psychological impact of the disease and its treatment."
      After evaluation of internal consistency, the UW-QOL was modified by removing 2
      domains that correlated poorly with the others. This resulted in a 10-item
      instrument (UW-QOL-R) with an overall internal consistency score of 0.85.
      CONCLUSIONS: The UW-QOL can be effectively and accurately used to compare
      treatment effects in the management of head and neck cancer. With this revised
      instrument, the 10 items appear to measure the domains of overall QOL in a highly
      consistent and reliable fashion over time.

PMID- 11346423
TI  - Impact of olfactory impairment on quality of life and disability.
AB  - OBJECTIVE: To determine whether olfactory loss affects patients' quality of life
      or level of disability. DESIGN: Retrospective survey using questionnaire data and
      clinic database review. SETTING: Two university medical center smell and taste
      clinics. PATIENTS: A total of 1407 patients were tested for smell and taste
      disturbances from 1984 through 1998. Surveys were mailed to 1093 patients who had
      abnormal test scores; 420 (38.4%) returned completed surveys. Patients were
      grouped by self-rated ability to smell as "impaired" (those reporting persisting
      deficits) or "improved" (those reporting no smell problem when surveyed). MAIN
      OUTCOME MEASURES: Response frequencies were compared between the 2 groups for
      questions regarding ability to perform common activities of daily living and
      quality-of-life issues. RESULTS: Mean (+/-SD) number of activities of daily
      living affected by olfactory loss was 4.70 +/- 3.56 for the impaired group and
      0.61 +/- 1.58 for the improved group (P < .001). Among specific activities, the
      most common cited impairments were ability to detect spoiled food (impaired vs
      improved groups, 75% vs 12%; P < .001), gas leaks (61% vs 8%; P < .001), or smoke
      (50% vs 1%; P < .001); eating (53% vs 12%; P < .001); and cooking (49% vs 12%; P
      < .001). Differences in quality-of-life issues were reported primarily in the
      areas of safety and eating. Overall satisfaction with life was reported by 87% of
      the improved group but only 50% of the impaired group (P < .001). CONCLUSIONS:
      Patients reporting persistent olfactory impairment after previously documented
      olfactory loss indicate a higher level of disability and lower quality of life
      than those with perceived resolution of olfactory compromise.

PMID- 11346424
TI  - Use of rigid and flexible bronchoscopy among pediatric otolaryngologists.
AB  - OBJECTIVE: To explore how rigid and flexible bronchoscopy are used in pediatric
      otolaryngologic practice. DESIGN: Survey. PARTICIPANTS: Members of the American
      Society of Pediatric Otolaryngology who practice in the United States and Canada
      and were listed in the membership directory were eligible. Of the 206 members, 24
      practicing outside the United States or Canada and 11 without an e-mail address
      or a fax machine were excluded. Hence, a questionnaire was e-mailed or faxed to
      171 pediatric otolaryngologists. MAIN OUTCOME MEASURES: Questions concerned the
      practice setting, type and number of bronchoscopies, indications, complications,
      and medicolegal cases. RESULTS: Responses were received from 120 subjects
      (70.2%), with 3 retired and 2 practicing only otology, leaving 115 respondents
      who completed at least some of the questionnaire. Rigid and flexible bronchoscopy
      were performed by 72.7% (56/77) of those in academic settings and by 71.1%
      (27/38) of those in group or solo practices. In the last 12 months, approximately
      10 454 total bronchoscopies were performed, with 2052 flexible and 9117 rigid
      bronchoscopies. Stridor, suspected foreign body inhalation, and laryngomalacia
      were the most common indications for bronchoscopy. Of the 83 respondents
      practicing rigid and flexible bronchoscopy, 25 (30.1%) used both instruments to
      manage complex or repeated foreign bodies, 25 (30.1%) used both to manage
      patients with cystic fibrosis, and 15 (18.1%) used both to manage simple foreign
      bodies. Complications were reported by 15.7% of the respondents, the most common
      being arrhythmia. Familiarity with a case resulting in medicolegal action was
      reported by 32.2% of the respondents. CONCLUSIONS: Rigid and flexible
      bronchoscopy have multiple uses in pediatric otolaryngologic practice. Also,
      flexible bronchoscopy appears to be emerging as a more frequently used diagnostic
      and therapeutic tool.

PMID- 11346425
TI  - Gastroesophageal reflux and pediatric otolaryngologic disease: the role of
      antireflux surgery.
AB  - OBJECTIVE: To determine the role of antireflux surgery in the treatment of
      gastroesophageal reflux-induced otolaryngologic disease (GEROD). DESIGN: A
      retrospective medical record analysis was performed. Patient demographics,
      otolaryngologic disease secondary to gastroesophageal reflux (GER), method of GER
      diagnosis, medical treatment used before antireflux surgery, and response to
      surgical intervention were considered. SETTING: Tertiary care children's
      hospital. PATIENTS: Among patients undergoing antireflux surgery between January
      1, 1996, and December 31, 1999, children with GEROD were included in the study.
      INTERVENTIONS: Children with GEROD who failed medical therapy underwent
      antireflux surgery. MAIN OUTCOME MEASURES: The demographics of patients requiring
      antireflux surgery for treatment of their otolaryngologic disease and their
      clinical response to surgery were reviewed. RESULTS: Fourteen (17%) of 82
      children, ranging in age from 48 days to 3 years (mean age, 9.7 months), who
      underwent antireflux surgery for GER at our institution between 1996 and 1999
      were diagnosed as having GEROD. Twelve (86%) of the 14 patients were found to
      have upper airway abnormalities, including subglottic edema, fixed subglottic
      stenosis, reflex apnea, and recurrent croup. Two patients (14%) had severe
      chronic sinusitis and otitis media. Nine (64%) of the 14 had normal neurologic
      function for their age vs 5 (36%) who had neurologic impairment. After antireflux
      surgery, all 14 patients with GEROD had complete resolution of clinical symptoms.
      CONCLUSIONS: Gastroesophageal reflux has an important role in the cause of
      numerous otolaryngologic disorders. Although medical management should remain the
      mainstay of GER therapy, antireflux surgery provided definitive and successful
      treatment of potentially life-threatening manifestations of GEROD.

PMID- 11346426
TI  - Low cord blood pneumococcal antibody concentrations predict more episodes of
      otitis media.
AB  - OBJECTIVE: To determine if cord blood anticapsular polysaccharide pneumococcal
      IgG antibody concentration was related to the number of otitis media (OM) and
      acute OM episodes during the first year of life. DESIGN: Prospective study
      following infants from birth to 24 months. SETTING: Health maintenance
      organization. PATIENTS: The study population consisted of 415 infants whose
      mothers volunteered for the study during pregnancy. Cord blood samples were
      collected and infants were followed up for OM in the health maintenance
      organization. Ninety-seven percent of the infants were white, 49% male, 3% from
      households with annual incomes of less than $20 000, and 30% from households with
      annual incomes of more than $60 000. MAIN OUTCOME MEASURE: Number of physician
      diagnosed OM episodes, including both OM with effusion and acute OM, and acute OM
      episodes from birth to 12 months. RESULTS: With univariate analysis, low cord
      blood antibody concentrations against serotypes 3 and 19F predicted more acute OM
      episodes (P =.04 and P =.05, respectively), and low antibody concentrations
      against serotypes 19F and 23F predicted more OM episodes (P =.04 and P =.05,
      respectively) over the first year of life. With Poisson regression, which
      adjusted for variables related to the recurrence of OM and having low cord blood
      antibody concentrations, serotype 19F remained significantly related to the
      number of OM episodes (relative risk for lowest quartiles vs upper 3 quartiles
      1.23; 95% confidence interval, 1.02-1.50; P =.03). CONCLUSIONS: Low cord blood
      antibody concentrations to serotype 19F predicted more OM episodes over the first
      12 months of life. These results suggest the potential benefit of maternal
      immunization to raise neonatal antipolysaccharide pneumococcal antibody
      concentration and delay the onset and reduce the number of OM episodes.

PMID- 11346427
TI  - Bacterial colonization of endotracheal tubes in intubated neonates.
AB  - OBJECTIVE: To obtain in vivo bacterial colonization profiles on endotracheal
      tubes at different sites in the neonatal airway in an attempt to better
      characterize one potential element of chondritis. DESIGN: A case series in which
      cultures were obtained from calculated segments of 33 endotracheal tubes
      immediately following extubation. This allowed for sampling at specific levels of
      the airway corresponding to the trachea, the subglottis, and the oropharynx. Data
      collected included gender, race, duration of intubation, use of antibiotic
      therapy, comorbidities, gestational age at birth and extubation, crown-rump
      length, weight, radiographic distance from tube tip to carina, and culture
      results. SETTING: Newborn intensive care unit at a tertiary care medical center.
      PATIENTS: Twenty-nine neonates intubated for longer than 24 hours (range, 24
      hours to 15 days). MAIN OUTCOME MEASURES: Bacterial and fungal cultures obtained
      from 3 endotracheal tube segments for each extubation. RESULTS: A statistically
      significant difference (P < .05) was found in colonization rates between patients
      intubated for less than 4 days and those intubated for longer periods. No
      significant difference was noted in bacterial profile between the 3 sites.
      CONCLUSIONS: Data demonstrate that bacterial colonization of an indwelling object
      in the neonatal airway increases with the duration of intubation. Furthermore, 4
      days seems to represent a critical period in the formation of such colonization
      (possibly in the form of a biofilm). These bacteria may contribute to the
      chondritis known to precede the development of subglottic stenosis. Further
      studies are indicated to suggest ways to interrupt this process and reduce the
      incidence of airway injury.

PMID- 11346428
TI  - N-chlorotaurine, a novel endogenous antimicrobial agent: tolerability testing in
      a mouse model.
AB  - OBJECTIVE: To investigate the tolerability of N-chlorotaurine, a new
      antimicrobial agent, by application to the middle ear in a mouse model. METHODS:
      Five BALB/c mice were each injected through the tympanic membrane with 5 microL
      of 0.1%, 1.0%, and 10% N-chlorotaurine and compared with animals in which 0.9%
      isotonic sodium chloride solution, 0.2% gentamicin sulfate, and 0.25%
      trimethyltin chloride were instilled. Auditory brainstem responses to clicks were
      evaluated repeatedly between 4 and 75 days after injection, and histologic
      investigations of the inner ear were performed subsequently. Three additional
      groups of mice were injected with isotonic sodium chloride solution, 1.0% N
      chlorotaurine, and 0.25% trimethyltin, and brainstem responses to tone bursts of
      8, 16, and 32 kHz were tested. In addition, the middle ear was examined
      histologically. RESULTS: Mice treated with isotonic sodium chloride solution,
      0.1% N-chlorotaurine, and 0.2% gentamicin sulfate did not show changes in
      response threshold. Treatment with 1.0% and 10% N-chlorotaurine caused a
      reversible increase in auditory brainstem response threshold by 20 dB 4 days
      after application because of local irritation around the perforation of the
      tympanic membrane. In contrast, 0.25% trimethyltin showed a permanent elevation
      of auditory brainstem response threshold of 10 to 15 dB and a scattered loss of
      outer hair cells predominantly in the apical turn. No alterations of the inner
      ear were observed in the other treatment groups. The mucous membrane of the
      middle ear remained unaffected in all test groups. CONCLUSION: Application of N
      chlorotaurine to the middle ear is well tolerated without adverse effects and may
      be a useful new endogenous antimicrobial agent for local treatment of otologic
      infections.

PMID- 11346429
TI  - Evaluation of esterified hyaluronic acid as middle ear-packing material.
AB  - OBJECTIVE: To evaluate the efficacy of esterified hyaluronic acid (MeroGel) as a
      middle ear (ME)-packing material. DESIGN: Randomized controlled trial. MATERIAL:
      Twenty-four guinea pigs. INTERVENTION: Group 1, MeroGel-treated animals (n = 10),
      bilateral wounding of ME mucosa with 5 of the animals receiving the MeroGel
      packing in the left ME and 5 of the animals receiving MeroGel in the right ME;
      group 2, absorbable gelatin sponge-treated animals (n = 10), with the same
      experimental protocol as in group 1 except that the absorbable gelatin sponge was
      the packing material; group 3, untreated animals (n = 4), unilateral wounding of
      the left ME mucosa in 2 animals and in 2 animals in the right ME, with no packing
      material. Auditory brainstem recordings were performed for all groups before the
      ME operation and 5 days and 6 weeks after the operation. RESULTS: Auditory
      brainstem response recordings at postoperative day 5 showed that all ears with ME
      packing had hearing losses in the frequency range of 500 to 4000 Hz. The recovery
      of hearing acuity at postoperative week 6 was significantly better in group 1
      (MeroGel-treated) guinea pigs compared with group 2 (the absorbable gelatin
      sponge-treated) animals. In group 2 animals, 20% of the packing material remained
      in the ME cavities and new bone formation was observed, while in group 1 animals,
      there was less packing material in the ME and no formation of new bone.
      CONCLUSIONS: MeroGel is a nonototoxic packing material with a high level of
      biocompatibility for ME mucosa; it is an effective supportive material following
      ME surgery and is easily expelled from the ME cavity.

PMID- 11346430
TI  - Facial function in hearing preservation acoustic neuroma surgery.
AB  - OBJECTIVE: To determine if facial function is worse after hearing preservation
      acoustic neuroma surgery (retrosigmoid and middle fossa) than in
      translabyrinthine surgery. DESIGN: Retrospective medical record review. SETTING:
      Private neuro-otology subspecialty practice of patients operated on in a tertiary
      care hospital. PATIENTS: This study evaluated 315 consecutive acoustic neuroma
      surgical procedures between April 1989 and July 1998. A total of 209
      translabyrinthine procedures and 106 hearing preservation surgical procedures
      were performed. The hearing preservation procedures were equally divided between
      retrosigmoid (n = 48) and middle fossa (n = 58) procedures. METHODS: Medical
      records were reviewed and tabulated for tumor size, surgical approach, and House
      Brackmann facial function grade at short-, intermediate-, and long-term
      intervals. RESULTS: Postoperative facial function in hearing preservation
      surgical procedures at short- and long-term follow-up was not worse than facial
      function after translabyrinthine surgical procedures in comparably sized tumors.
      CONCLUSION: Concern about postoperative facial function should not be the
      deciding factor in selecting hearing preservation vs nonhearing preservation
      acoustic neuroma surgery.

PMID- 11346431
TI  - Influence of minor ear surgery on infrared tympanic thermometry.
AB  - BACKGROUND: Infrared tympanic thermometry (ITT) is often used for postoperative
      recovery room monitoring regardless of recent minor otologic surgery. OBJECTIVE:
      To evaluate the use of ITT in pediatric patients who have undergone bilateral
      myringotomy with insertion of pressure-equalizing tubes. DESIGN: A prospective
      cohort study. SETTING: Tertiary care academic medical center. PATIENTS:
      Consecutive patients of a staff pediatric otolaryngologist (M.A.R.): (1) ear
      surgery group, children aged 10 years or younger undergoing bilateral myringotomy
      with insertion of pressure-equalizing tubes and (2) non-ear surgery group,
      children aged 10 years or younger undergoing bilateral tonsillectomy with or
      without adenoidectomy. INTERVENTIONS: Immediate preprocedure temperature
      measurements included right and left ear ITT. Immediate postprocedure temperature
      measurements included right and left ear ITT and thermistor probe rectal
      temperature. MAIN OUTCOME MEASURES: The average difference between the
      preprocedure and postprocedure tympanic temperature in the ear surgery group was
      compared with that in the non-ear surgery group. The average difference between
      postprocedure rectal and ear temperature in the ear surgery group was compared
      with that in the non-ear surgery group. RESULTS: There were 20 patients (40 ears)
      in the ear surgery group and 20 patients (40 ears) in the non-ear surgery group.
      In the ear surgery group, the average difference between the preprocedure and
      postprocedure tympanic temperature (0.55 degrees C) was not significantly
      different from that (0.62 degrees C) in the non-ear surgery group (P =.66, 1-way
      analysis of variance). In the ear surgery group, the average difference between
      postprocedural rectal and ear temperature (1.94 degrees C) was not significantly
      different from that (1.89 degrees C) in the non-ear surgery group (P =.76, 1-way
      analysis of variance). CONCLUSION: Recent minor ear surgery (bilateral
      myringotomy with insertion of pressure-equalizing tubes) does not have a
      significant effect on ITT measurements in pediatric patients.

PMID- 11346432
TI  - Effects of difluoromethylornithine chemoprevention on audiometry thresholds and
      otoacoustic emissions.
AB  - OBJECTIVES: To determine the effects of long-term, low-dose
      difluoromethylornithine (DFMO) on audiometric thresholds and distortion product
      otoacoustic emission (DPOAE) levels in humans. DESIGN: A prospective, randomized,
      placebo-controlled phase 2 clinical trial of DFMO in participants with a prior
      adenomatous colonic polyp. SETTING: Academic tertiary care referral center.
      PARTICIPANTS: One hundred twenty-three volunteer subjects with colorectal polyps
      and normal hearing for the frequencies 250 through 2000 Hz. INTERVENTIONS:
      Subjects were randomized to receive placebo or oral DFMO at daily dosages between
      0.075 and 0.4 g/m(2) of body surface area for 12 months. OUTCOME MEASURES: Pure
      tone audiometric thresholds for the frequencies 250, 500, 1000, 2000, 3000, 4000,
      6000, and 8000 Hz and DPOAE levels were measured at baseline and 1, 3, 6, 9, and
      12 months after starting treatment with DFMO or placebo and 3 months after
      cessation of treatment if there was a suggestion of possible changes at the 12
      month measurement. RESULTS: At these low dosages, there was little evidence for
      shifts in auditory pure-tone thresholds, and there were no statistically
      significant shifts in DPOAE levels. For auditory pure-tone thresholds, there was
      a subtle, approximately 2- to 3-dB hearing level decrease in hearing sensitivity
      for the 2 higher DFMO dosages, but only at the 2 lowest frequencies, 250 and 500
      Hz. CONCLUSIONS: Administration of low-dose DFMO for 12 months did not produce
      hearing loss, in contrast to prior studies that used higher dosages.

PMID- 11346433
TI  - A study of inflammatory mediators in the human tympanosclerotic middle ear.
AB  - OBJECTIVE: To analyze immunocompetent cells as well as 2 factors involved in
      inflammation and also thought to be involved in bone remodeling-interleukin 6 (IL
      6) and inducible nitric oxide synthase in the human middle ear, including the
      tympanic membrane. DESIGN: Biopsy specimens were obtained from the human middle
      ear and tympanic membrane during surgery. Using an immunohistochemical technique,
      the expression of macrophages, T cells, B cells, IL-6, and inducible nitric oxide
      synthase were analyzed. MATERIALS: Nine biopsy specimens from tympanic membranes
      in children having a transtympanic ventilation tube inserted as a treatment for
      secretory otitis media and 11 biopsy specimens from tympanosclerotic plaques from
      patients with chronic otitis media and tympanosclerosis. RESULTS: More positively
      stained specimens showing macrophages, B cells, and IL-6 were seen in the biopsy
      specimens from children with secretory otitis media compared with the biopsy
      specimens from patients with chronic otitis media and tympanosclerosis. The
      biopsy specimens from patients with chronic otitis media and tympanosclerosis
      more often showed positive stainings for inducible nitric oxide synthase than the
      biopsy specimens from children with secretory otitis media. The presence of IL-6
      and inducible nitric oxide synthase was shown by staining to be mostly in the
      surface cells, while macrophages and B cells were stained deeper in the tissues,
      in connective tissue, or around sclerotic lesions. CONCLUSIONS: The 2 patient
      groups differed in antigen presentation so that macrophages, B cells, and IL-6
      were labeled more frequently in patients with secretory otitis media, that is, an
      early phase of the disease. Inducible nitric oxide synthase was seen more
      frequently in the patients with already established tympanosclerosis in a later
      phase of the disease.

PMID- 11346434
TI  - A diagnostic and therapeutic approach to paragangliomas of the larynx.
AB  - BACKGROUND: Differentiating paragangliomas from moderately differentiated
      neuroendocrine carcinoma in the larynx is a difficult management problem. As the
      biological behavior of these 2 entities is different, we developed an algorithm
      for the preoperative diagnosis and treatment of this disease. DESIGN: The sample
      case from which the algorithm was developed consisted of a 69-year-old man who
      was transferred to us after tracheostomy and an attempt at biopsy for airway
      obstruction secondary to a vascular mass. Biopsy resulted in substantial
      bleeding. Flexible laryngoscopy showed a vascular mass of the supraglottis. A
      computed tomographic scan showed 2 vascular masses at the carotid bifurcation and
      in the larynx. An arteriogram confirmed synchronous vascular tumors. RESULTS: The
      arteriogram showed the superior thyroid artery to be the major feeder vessel to
      this mass, a situation commonly seen in paragangliomas but not other
      neuroendocrine tumors. The presence of synchronous lesions and a vascular mass
      based on the superior thyroid artery helped differentiate paraganglioma from the
      other neuroendocrine tumors. As the biological behavior of paragangliomas is
      relatively benign, we performed a conservative supraglottic laryngectomy and
      excision of the carotid body tumor. Histologic diagnosis and immunohistochemical
      analysis confirmed the diagnosis of paraganglioma. CONCLUSIONS: The vascular
      nature of neuroendocrine tumors prevents preoperative pathological diagnosis.
      Radiologic features demonstrating a vascular mass with a dominant feeder vessel
      by the superior or inferior thyroid artery may help in the clinical diagnosis of
      paragangliomas of the larynx. Since paragangliomas are rarely malignant, a
      conservative surgical procedure should suffice.

PMID- 11346435
TI  - Laryngotracheal reconstruction in canines: fixation of autologous costochondral
      grafts using polylactic and polyglycolic acid miniplates.
AB  - OBJECTIVE: To examine the feasibility of a new method of laryngotracheal
      reconstruction (LTR) that uses a bioabsorbable plating system consisting of
      polylactic and polyglycolic acid and provides some advantages over currently used
      methods. DESIGN AND INTERVENTIONS: Anterior subglottic stenosis was created in 10
      beagles that then underwent LTR using an autologous costochondral graft. External
      laryngotracheal framework and cartilage grafts were secured using a sheet and
      screws made from a copolymer composed of polylactic and polyglycolic acid.
      Animals were humanely killed at 40, 60, and 90 days, and specimens were submitted
      for pathological examination. Histologic analysis included evaluation for
      inflammatory reaction, polylactic and polyglycolic acid incorporation into
      cartilage, cartilage necrosis, cartilage remodeling, and graft epithelialization.
      RESULTS: All animals underwent LTR after creation of a subglottic stenosis
      without episodes of airway compromise. After LTR, all airways were returned to
      prestenosis diameter without significant complication, and all animals were
      immediately extubated after surgery without difficulty. After the animals were
      killed, distraction of the stenotic cricoid area was demonstrated in 100% of the
      cases. Significant necrosis was noted in 2 of 10 grafts grossly; however,
      histologic analysis demonstrated significant areas of viable cartilage, areas of
      cartilage remodeling, and good epithelialization despite graft necrosis. Complete
      epithelialization of grafts was noted in the other 8 specimens. CONCLUSIONS:
      Using a canine model, we demonstrated a bioabsorbable plating system that offers
      an effective method for LTR. This model has the advantages of providing external
      support to the operated laryngeal and tracheal framework, elimination of the
      difficulties of suture placement, and potential future failure while offering
      rigid external fixation of a cartilage graft.

PMID- 11346436
TI  - Simulated reflux and laryngotracheal reconstruction: a rabbit model.
AB  - OBJECTIVES: (1) To test the feasibility of a rabbit model using a pharyngostomy
      tube to simulate gastroesophageal reflux and (2) to study the effects of
      gastroesophageal reflux on laryngotracheal reconstruction using a new rabbit
      model. DESIGN: Prospective randomized trial. SUBJECTS: Thirty-three New Zealand
      white rabbits. INTERVENTIONS: Anterior cartilage laryngotracheoplasty and
      pharyngostomy tube placement into the pyriform sinus were performed in 33
      rabbits, 22 of which are included in this analysis. Beginning postoperative day
      1, hydrochloric acid at a pH of 1.5 with pepsin (n = 7) or at a pH of 4.0 with
      pepsin (n = 8) was irrigated twice daily through the pharyngostomy tube to
      simulate gastroesophageal reflux, and a control group received twice-daily
      isotonic sodium chloride solution irrigations (n = 7). MAIN OUTCOME MEASURES:
      Specimens were scored by a pathologist masked to individual groups using a newly
      modified inflammation scoring system. In addition, cross-sectional areas of the
      cartilage grafts and subglottic airway lumina were compared. RESULTS:
      Inflammation scores were significantly higher in rabbits receiving hydrochloric
      acid and pepsin irrigations at a pH of 4.0 (P =.04) but not in those in the pH
      1.5 group. Cartilage necrosis was prominent in all groups, and airway sizes and
      cross-sectional areas of the grafts were not significantly different among the 3
      groups. CONCLUSIONS: Cartilage necrosis is prominent during the early stages
      after laryngotracheoplasty. Inflammation can be increased using hydrochloric acid
      and pepsin irrigations but is difficult to predict based on this study. Although
      we confirmed the feasibility of this model, further modifications of this study
      are proposed to improve animal survival and data collection.

PMID- 11346437
TI  - Quantitative assay of telomerase activity in head and neck squamous cell
      carcinoma and other tissues.
AB  - OBJECTIVES: To confirm the applicability and use of a new technique to detect and
      quantify telomerase activity of specimens from head and neck malignant neoplasms
      and to explore whether the levels of telomerase activity can be a useful marker
      for cancer risk assessment in head and neck malignant neoplasms. DESIGN: Ninety
      six specimens from 39 patients with head and neck malignant neoplasms were
      obtained. The specimens included 39 from patients with primary tumors (25 with
      head and neck squamous cell carcinoma and 14 with others), 10 from patients with
      neck metastases, 10 from patients with dysplasias, and 37 from patients with
      normal tissue. HeLa cell lines were used as positive control samples. MAIN
      OUTCOME MEASURE: The levels of telomerase activity were determined using a liquid
      scintillation counter. RESULTS: The new method has a high rate of outcome
      reproducibility. The intrabatch and extrabatch variations were 15.6% and 16.4%,
      respectively. The linear relationship was good between the telomerase activity
      and the value within 700 radioactive cpm (rcpm) to approximately 7000 rcpm. The
      levels of telomerase activity determined by radioactive count were more than 1000
      rcpm in 42 of the 49 malignant specimens and much more than that in the normal
      tissues, with the exception of 3 specimens. The levels of telomerase activity in
      normal tissues were less than 1000 rcpm in every sample and less than that in the
      malignant neoplasm samples, with the exception of 1 specimen (P < .000). Higher
      levels of telomerase activity in 2 of 10 tissues from patients who had dysplasias
      were detected (2 specimens from patients who had severe dysplasia). The
      differences in the levels of telomerase activity between the head and neck
      squamous cell carcinomas and the other tumors were not statistically significant
      (P > .05). CONCLUSIONS: Detection of telomerase activity in head and neck
      malignant neoplasms can be a useful marker for the assessment of cancer.
      Telomerase reactivation may play an important role in tumorigenesis in head and
      neck squamous cell carcinoma. The quantification of telomerase activity may have
      clinical diagnostic value for head and neck malignant neoplasms.

PMID- 11346438
TI  - Chronic cough: an unusual cause, an unusual cure.

PMID- 11346439
TI  - Sphenoethmoid cerebrospinal fluid leak repair with hydroxyapatite cement.
AB  - Despite advances in neurological, reconstructive, and endoscopic sinus surgery,
      sphenoethmoid cerebrospinal fluid (CSF) fistulae continually pose difficult
      management problems. Standard surgical techniques for fistulae closure succeed
      approximately 78% to 90% of the time. To improve this success rate,
      hydroxyapatite cement (HAC), a Food and Drug Administration-approved substance
      for cranial defect repair, was applied to this problem in a clinical setting.
      Twenty-one patients with spontaneous, posttraumatic, or postoperative CSF leaks
      of the sphenoid sinus, cribriform plate, or ethmoid region were treated with HAC.
      Study participants were prospectively accrued at 5 tertiary care medical centers
      in the eastern United States. The CSF leaks of all 21 patients treated with HAC
      were successfully sealed by its initial application. The sites of CSF leakage
      included the nasal cavity (n = 2) and sphenoid sinus (n = 19). Fifteen of the
      patients had previously undergone a failed repair by standard methods. There have
      been no recurrent CSF leaks with a maximum follow-up of 72 months, and an average
      follow-up of 36 months. All patients have survived to date. The only HAC-related
      morbidity was the extrusion of the HAC when placed in the nasal cavity.
      Hydroxyapatite cement is an effective method of repair for postoperative,
      posttraumatic, and spontaneous sphenoid CSF leaks. The efficacy of HAC in sealing
      the CSF leak was unaffected by previous attempts at leak closure by standard
      methods or by its origin. Hydroxyapatite cement should not be applied
      transnasally for the treatment of an ethmoid region fistula owing to its high
      probability of extrusion. Correct patient selection and technical familiarity
      with HAC are necessary for successful application.

PMID- 11346440
TI  - Pathology forum: quiz case 1. Early medullary thyroid carcinoma (MTC), familial
      type, arising in a background of C-cell hyperplasia.

PMID- 11346441
TI  - Pathology forum: quiz case 2. Mucoepidermoid carcinoma (intermediate grade) of
      the trachea.

PMID- 11346442
TI  - Internet marketing offers an excellent potential for increasing one's practice.

PMID- 11346443
TI  - Not yet ready for prime time.

PMID- 11346444
TI  - Internet marketing essential to physician and patient successes.

PMID- 11346445
TI  - Traumatic Brain Injury Collaborative Planning Group: a protocol for community
      intervention.
AB  - OBJECTIVE: The Traumatic Brain Injury Collaborative Planning Group was formed in
      December 1992 to address service gaps and better use agencies and their programs
      to meet the specialized needs of individuals with traumatic brain injury (TBI).
      SETTING: The group meetings served as the interagency link between service
      providers for comprehensive planning and problem solving. OUTCOME MEASURES: This
      article focuses on the three main tasks of this group: (1) interagency case
      planning among participating agencies; (2) provision of training and networking
      opportunities for service providers working with this population; (3) development
      of creative funding mechanisms for community education and support services to
      assist individuals to live and work in the community. METHODS: The methods used
      to organize the collaborative, direct it toward the three main tasks, and
      maintain it without any agency funding are outlined. RESULTS: Data collected
      about the 21 persons served in the past 3 years is provided, and protocol forms
      are shared. CONCLUSION: This model of collaboration throughout a countywide area
      has been used as a basis for similar development in several other states.

PMID- 11346446
TI  - Factors associated with balance deficits on admission to rehabilitation after
      traumatic brain injury: a multicenter analysis.
AB  - OBJECTIVE: To evaluate how demographics, measures of injury severity, and acute
      care complications relate to sitting and standing balance in patients with
      traumatic brain injury (TBI). DESIGN: Multicenter analysis of consecutive
      admissions to designated TBI Model Systems of Care (TBIMS). SETTING: Ten National
      Institute for Disability and Rehabilitation Research TBI Model System centers for
      coordinated acute and rehabilitation care. PARTICIPANTS: 908 adults with TBI were
      included in the study. MAIN OUTCOME MEASURES: Sitting and standing balance were
      assessed within 72 hours of admission to inpatient rehabilitation. RESULTS: Age
      less than 50 years had a significant association with normal sitting and standing
      balance (P =.001 and.05, respectively). Measures of severity of traumatic brain
      injury, including admission Glasgow Coma Score, length of posttraumatic amnesia
      (PTA), length of coma, and acute care length of stay were each significantly
      related to impaired sitting and standing balance ratings (P <.01). Initial
      abnormalities in pupillary response had a significant relationship with
      impairment of sitting (P =.009) but not standing balance. Incidence of
      respiratory failure, pneumonia, soft tissue infections, and urinary tract
      infections were all related to impaired sitting balance (P <.01). Presence of
      intracranial hemorrhages did not have a significant relationship with either
      sitting or standing balance. Intracranial compression had a significant
      relationship with standing (P =.05) but not sitting balance. A discriminant
      function analysis, which included neuroradiological findings, injury severity,
      and medical complications, could not accurately predict impaired balance ratings.
      CONCLUSIONS: This study demonstrated that rehabilitation admission balance
      ratings have a significant relationship with age, multiple measures of severity,
      and acute care medical complications after TBI. Prospective studies are indicated
      to evaluate the role balance at rehabilitation admission plays in the functional
      prognosis of patients with TBI.

PMID- 11346447
TI  - Quantitative PET findings in patients with posttraumatic anosmia.
AB  - OBJECTIVE: To investigate quantitative positron emission tomography (PET)
      findings, particularly from orbitofrontal cortex, in patients with posttraumatic
      anosmia. SETTING: Neuropsychology outpatient clinic and university brain imaging
      center. SUBJECTS: Eleven patients with head injury resulting in severe anosmia
      and 11 controls matched for age. All 11 head-injured patients had their head
      injuries at least 2 years before involvement in the study. MEASURES: Regional
      cerebral glucose metabolism was measured with PET. RESULTS: Quantitative
      evaluation of PET findings for anosmic patients as a group showed orbitofrontal
      hypometabolism compared with controls. Decreased activity was also noted in
      mesial temporal lobe. Activity in subcortical white matter was essentially
      identical between groups. CONCLUSIONS: Findings strongly suggest that
      posttraumatic anosmia is closely associated with hypometabolism in the
      orbitofrontal cortex and the medial prefrontal cortex. The results also
      underscore the importance of posttraumatic anosmia as a clinical sign of
      orbitofrontal damage, as has been shown previously with neuroSPECT (single photon
      emission computed tomography).

PMID- 11346448
TI  - Flexyx Neurotherapy System in the treatment of traumatic brain injury: an initial
      evaluation.
AB  - OBJECTIVE: To conduct a preliminary experimental evaluation of the potential
      efficacy of Flexyx Neurotherapy System (FNS), an innovative
      electroencephalography (EEG)-based therapy used clinically in the treatment of
      traumatic brain injury (TBI). PARTICIPANTS: Twelve people aged 21 to 53 who had
      experienced mild to moderately severe closed head injury at least 12 months
      previously and who reported substantial cognitive difficulties after injury,
      which interfered with their functioning. DESIGN: Participants were randomly
      assigned to an immediate treatment group or a wait-list control group and
      received 25 sessions of FNS treatment. They were assessed at pretreatment,
      posttreatment, and follow-up with standardized neuropsychological and mood
      measures. RESULTS: Comparison of the two groups on outcome measures indicated
      improvement after treatment for participants' reports of depression, fatigue, and
      other problematic symptoms, as well as for some measures of cognitive
      functioning. Most participants experienced meaningful improvement in occupational
      and social functioning. CONCLUSION: On the basis of these results, FNS appears to
      be a promising new therapy for TBI and merits more extensive evaluation.

PMID- 11346449
TI  - Incremental validity of the MMPI-2 Content Scales: a preliminary study with brain
      injured patients.
AB  - OBJECTIVE: To examine the usefulness of the MMPI-2 Content Scales among traumatic
      brain injury (TBI) patients. DESIGN: Hierarchical stepwise regression analyses
      with the SCL-90-R scales as the criterion variables were conducted to determine
      the incremental validity of the Content Scales beyond the information provided by
      the Clinical Scales. PARTICIPANTS: 27 persons with moderate to severe TBI who had
      been discharged to the community from inpatient rehabilitation between 6 months
      and 4 years before the beginning of the study. RESULTS: The Content Scales
      accounted for an additional 4% to 36% of the variance of SCL-90-R scales beyond
      that predicted by the Clinical Scales. CONCLUSIONS: Interpretation of the Content
      Scales may be particularly valuable with TBI patients, because they provide an
      additional avenue for the identification of distressing symptoms.

PMID- 11346450
TI  - Using talking lights to assist brain-injured patients with daily inpatient
      therapeutic schedule.
AB  - OBJECTIVES: To test the ability of patients with brain injury to use a patient
      locator and minder (PLAM) system to assist in their adherence to therapy
      schedules. PARTICIPANTS: Five patients with acquired brain injury who were
      inpatients on an acute rehabilitation floor of a rehabilitation hospital.
      MEASURES: The number of human prompts necessary to direct a patient to, and
      ensure arrival at, a scheduled therapy destination and the proportion of therapy
      sessions requiring no prompting was measured both before and after the
      introduction of the PLAM system. RESULTS: With the PLAM system, the average
      number of human prompts dropped by more than 50%, and the number of sessions
      requiring no prompting increased from 7% to 44%. CONCLUSION: The PLAM system
      described in this article seems feasible and useful for patients with acquired
      brain injury in assisting them with arrival at their therapy destinations without
      the assistance of staff.

PMID- 11346451
TI  - Activity restrictions as part of the discharge management for children with a
      traumatic head injury.
AB  - This article describes a proactive management strategy that is currently part of
      the discharge protocol for children seeking care for a head injury (HI) at a
      pediatric and adolescent trauma center. The strategy consists of setting activity
      restrictions for children hospitalized and those seen in the emergency department
      after a HI that may or not have been sports related. It was developed based on
      extensive clinical experience with families of children with a HI and existing
      guidelines for returning athletes to sports. Possible merits and pitfalls of the
      strategy are discussed.

PMID- 11346452
TI  - A case of antidepressant-induced akathisia in a patient with traumatic brain
      injury.

PMID- 11346453
TI  - Calcium dynamics during fertilization in C. elegans.
AB  - BACKGROUND: Of the animals typically used to study fertilization-induced calcium
      dynamics, none is as accessible to genetics and molecular biology as the model
      organism Caenorhabditis elegans. Motivated by the experimental possibilities
      inherent in using such a well-established model organism, we have characterized
      fertilization-induced calcium dynamics in C. elegans. RESULTS: Owing to the
      transparency of the nematode, we have been able to study the calcium signal in C.
      elegans fertilization in vivo by monitoring the fluorescence of calcium indicator
      dyes that we introduce into the cytosol of oocytes. In C. elegans, fertilization
      induces a single calcium transient that is initiated soon after oocyte entry into
      the spermatheca, the compartment that contains sperm. Therefore, it is likely
      that the calcium transient is initiated by contact with sperm. This calcium
      elevation spreads throughout the oocyte, and decays monotonically after which the
      cytosolic calcium concentration returns to that preceding fertilization. Only
      this single calcium transient is observed. CONCLUSION: Development of a technique
      to study fertilization induced calcium transients opens several experimental
      possibilities, e.g., identification of the signaling events intervening sperm
      binding and calcium elevation, identifying the possible roles of the calcium
      elevation such as the completion of meiosis, the formation of the eggshell, and
      the establishing of the embryo's axis of symmetry.

PMID- 11346455
TI  - Message to complementary and alternative medicine: evidence is a better friend
      than power.
AB  - BACKGROUND: Evidence-based medicine (EBM) is being embraced by an increasing
      number of practitioners and advocates of complementary and alternative medicine
      (CAM). A significant constituency within CAM, however, appears to have
      substantive doubts about EBM and some are expressly hostile. DISCUSSION: Many of
      the arguments raised against EBM within the CAM community are based on a
      caricature radically at odds with established, accepted and published principles
      of EBM practice. Contrary to what has sometimes been argued, EBM is not cookbook
      medicine that ignores individual needs. Neither does EBM mandate that only proven
      therapies should be used. Before EBM, decisions on health care tended to be based
      on tradition, power and influence. Such modes usually act to the disadvantage of
      marginal groups. CONCLUSION: By placing CAM on an equal footing with conventional
      medicine - what matters for both is evidence of effectiveness - EBM provides an
      opportunity for CAM to find an appropriate and just place in health care.

PMID- 11346454
TI  - Immunocytochemical evidence for co-expression of Type III IP3 receptor with
      signaling components of bitter taste transduction.
AB  - BACKGROUND: Taste receptor cells are responsible for transducing chemical stimuli
      into electrical signals that lead to the sense of taste. An important second
      messenger in taste transduction is IP3, which is involved in both bitter and
      sweet transduction pathways. Several components of the bitter transduction
      pathway have been identified, including the T2R/TRB taste receptors,
      phospholipase C beta2, and the G protein subunits alpha-gustducin, beta3, and
      gamma13. However, the identity of the IP3 receptor subtype in this pathway is not
      known. In the present study we used immunocytochemistry on rodent taste tissue to
      identify the IP3 receptors expressed in taste cells and to examine taste bud
      expression patterns for IP3R3. RESULTS: Antibodies against Type I, II, and III
      IP3 receptors were tested on sections of rat and mouse circumvallate papillae.
      Robust cytoplasmic labeling for the Type III IP3 receptor (IP3R3) was found in a
      large subset of taste cells in both species. In contrast, little or no
      immunoreactivity was seen with antibodies against the Type I or Type II IP3
      receptors. To investigate the potential role of IP3R3 in bitter taste
      transduction, we used double-label immunocytochemistry to determine whether IP3R3
      is expressed in the same subset of cells expressing other bitter signaling
      components. IP3R3 immunoreactive taste cells were also immunoreactive for
      PLCbeta2 and gamma13. Alpha-gustducin immunoreactivity was present in a subset of
      IP3R3, PLCbeta2, and gamma13 positive cells. CONCLUSIONS: IP3R3 is the dominant
      form of the IP3 receptor expressed in taste cells and our data suggest it plays
      an important role in bitter taste transduction.

PMID- 11346456
TI  - Clinical ethics revisited.
AB  - A decade ago, we reviewed the field of clinical ethics; assessed its progress in
      research, education, and ethics committees and consultation; and made predictions
      about the future of the field. In this article, we revisit clinical ethics to
      examine our earlier observations, highlight key developments, and discuss
      remaining challenges for clinical ethics, including the need to develop a global
      perspective on clinical ethics problems.

PMID- 11346458
TI  - Expression of gp34 (OX40 ligand) and OX40 on human T cell clones.
AB  - gp34, which we previously cloned, is a ligand of OX40 (CD134), a costimulatory
      molecule involved in T cell activation. To elucidate the role of human OX40 /
      OX40L interaction, we examined the expression of gp34 (OX40L) and OX40 in normal
      human hematopoietic cells by using flow cytometry. OX40 expression is observed on
      activated T cells, while OX40L is expressed in antigen-presenting cells. However,
      cytotoxic T lymphocyte (CTL) clones specific for Epstein-Barr virus (EBV)
      transformed autologous lymphoblastic cell lines (LCLs) induced both OX40 and
      OX40L expression after antigen or T cell receptor (TCR) stimulation. This study
      suggests a possible function of OX40L / OX40, through T cell-T cell interaction,
      in the reactivation of memory T cells in an autocrine manner, with implications
      for the pathogenesis of viral infections and neoplasms.

PMID- 11346457
TI  - Clinical ethics revisited: responses.

PMID- 11346459
TI  - Interleukin 1 polymorphisms, lifestyle factors, and Helicobacter pylori
      infection.
AB  - Associations between Helicobacter pylori (HP) infection and lifestyle factors
      have been reported by several authors, but little is known about the host factors
      associated with the infection. This study aims to examine the infection rate of
      HP according to gene polymorphisms of interleukin (IL)-1A, IL-1B, and IL-1RN, and
      to investigate the interactions with lifestyle factors. Subjects were 241 non
      cancer outpatients who had participated in a HP eradication program.
      Polymorphisms at - 889 (T to C) of IL-1A, at - 31 (C to T; T allele makes a TATA
      box) and - 511 (C to T) of IL-1B, and at intron 2 (86-bp VNTR (variable number of
      tandem repeats)) of IL-1RN were genotyped by PCR (polymerase chain reaction), PCR
      RFLP (restriction fragment length polymorphism) and PCR-CTPP (PCR with
      confronting two-pair primers). It was found that IL-1B polymorphisms at - 31 and 
      511 were near-completely linked, but in the opposite way to that in Caucasians; 
      31C / - 511T and - 31T / - 511C alleles were dominant in the present subjects.
      The HP infection rate was substantially different among the genotypes of IL-1B C 
      31T; 45.2% (19 / 42) for the C / C, 67.7% (90 / 133) for the C / T, and 63.6%
      (42 / 66) for the T / T. The age-sex adjusted odds ratio (OR) relative to the C /
      C genotype was 2.32 (95%CI (confidence interval), 1.10 - 4.92) for the T / C
      genotype and 2.46 (1.06 - 5.74) for the T / T genotype. The OR for the T / T
      genotype was significantly modified by smoking status; interaction term = 14.6
      (1.12 - 190). The polymorphisms of IL-1A and IL-1RN were not associated with the
      infection rate. The results suggested that the T allele of IL-1B C - 31T is
      associated with vulnerability to persistent HP infection, and that the
      vulnerability is modified by smoking.

PMID- 11346460
TI  - Synergistic effects of high-dose soybean intake with iodine deficiency, but not
      sulfadimethoxine or phenobarbital, on rat thyroid proliferation.
AB  - The specificity and dose dependence of the synergistic effects of soybean intake
      with iodine deficiency on the induction of thyroid proliferation were
      investigated in female F344 rats. In the first experiment, rats were divided into
      6 groups, each consisting of 5 animals, and fed a basal diet containing 20%
      gluten, an iodine-deficient basal diet alone or an iodine-deficient diet
      containing 0.2%, 1.0%, 5.0% or 25% defatted soybean for 5 weeks. Soybean feeding
      synergistically induced thyroid hyperplasias with iodine deficiency only at the
      25% dose. In the second experiment, rats were also divided into 6 groups, each
      consisting of 5 animals, and fed a basal diet, a diet containing 20% defatted
      soybean, 0.025% sulfadimethoxine (SDM), 20% defatted soybean + 0.025% SDM, 0.05%
      phenobarbital (PB) or 20% defatted soybean + 0.05% PB for 5 weeks. The SDM
      treatments significantly (P < 0.05 - 0.01) increased the thyroid weights, but
      this increase rate was less prominent in the SDM + soybean group than in the SDM
      alone group. The PB treatment was also associated with a tendency for increase in
      thyroid weight, but again this was smaller in the PB + soybean group than in the
      PB alone group. Although the SDM or PB treatments reduced the serum
      triiodothyronine and thyroxine levels and consequently increased the serum
      thyroid-stimulating hormone (TSH) levels, the soybean feeding did not affect or
      rather attenuated these changes. Our results clearly indicate that soybean
      feeding does not synergistically enhance the effects of SDM or PB on the rat
      thyroid. Thus it can be concluded that soybean intake specifically interacts with
      iodine deficiency in induction of thyroid proliferative lesions in rats, only at
      high doses.

PMID- 11346461
TI  - Troglitazone, a ligand for peroxisome proliferator-activated receptor gamma,
      inhibits chemically-induced aberrant crypt foci in rats.
AB  - The biological roles of peroxisome proliferator-activated receptors (PPARs) in
      various diseases, including inflammation and cancer, have been highlighted
      recently. Although PPARgamma ligand is suspected to play an important role in
      carcinogenesis, its effects on colon tumorigenesis remain undetermined. The
      present time-course study was conducted to investigate possible modifying effects
      of a PPARgamma ligand, troglitazone, on the development and growth of aberrant
      crypt foci (ACF), putative precursor lesions for colon carcinoma, induced by
      azoxymethane (AOM) or dextran sodium sulfate (DSS) in male F344 rats. Oral
      troglitazone (10 or 30 mg / kg body weight (b.w.)) significantly reduced AOM (two
      weekly subcutaneous injections, 20 mg / kg b.w.)-induced ACF. Treatment with
      troglitazone increased apoptosis and decreased polyamine content and ornithine
      decarboxylase (ODC) activity in the colonic mucosa of rats treated with AOM.
      Gastric gavage of troglitazone also inhibited colitis and ACF induced by DSS (1%
      in drinking water), in conjunction with increased apoptosis and reduced colonic
      mucosal polyamine level and ODC activity. Our results suggest that troglitazone,
      a synthetic PPARgamma ligand, can inhibit the early stage of colon tumorigenesis
      with or without colitis.

PMID- 11346462
TI  - A ferulic acid derivative, ethyl 3-(4'-geranyloxy-3-methoxyphenyl)-2-propenoate,
      as a new candidate chemopreventive agent for colon carcinogenesis in the rat.
AB  - The inhibitory influence of ferulic acid (FA), a rice germ component, and its
      geranylated derivative 3-(4'-geranyloxy-3-methoxyphenyl)-2-propenoate (EGMP) on
      the post-initiation stage of azoxymethane (AOM)-induced colon carcinogenesis was
      studied in male F344 rats given two s.c. injections of AOM (15 mg / kg body
      weight) during week 1. Diets containing EGMP or FA at doses of 0.1 or 0.2% were
      then fed for 3 weeks from week 2 to 5, when the animals were sacrificed. The
      numbers of aberrant crypt foci (ACF) and aberrant crypts (AC) per rat in the
      group given 0.2% FA were significantly decreased (P < 0.001) as compared to the
      AOM alone group. Furthermore, the numbers of ACF and AC per rat fed the 0.2% and
      0.1% EGMP were significantly reduced (P < 0.001 and P < 0.01, respectively).
      Colonic epithelial cells in S-phase, as measured by bromodeoxyuridine (BrdU)
      labeling, in rats fed EGMP were significantly decreased in the 0.2 and 0.1% EGMP
      groups as compared to the AOM alone group (P < 0.05). BrdU labeling indices in
      rats fed FA and EGMP assessed by a test using a coefficient for linear contrast
      were also significantly decreased as compared to the AOM alone value (P < 0.05, P
      < 0.01, respectively). The results indicate that FA and EGMP have inhibitory
      effects on ACF and AC development, EGMP being more potent, possibly due to
      stronger suppressive effects on cell proliferation. No toxic effects were
      observed in rats given either compound in terms of body and organ weights, and
      liver or kidney histology. The findings thus suggest that EGMP and FA, especially
      the former, might have potential as chemopreventive agents against colon tumor
      development.

PMID- 11346463
TI  - Cell-free entry of human T-cell leukemia virus type 1 to mouse cells.
AB  - Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent for adult T
      cell leukemia and HTLV-1-associated myelopathy / tropical spastic paraparesis.
      Recently we infected newborn mice by inoculating HTLV-1-producing human cells,
      and found that T-cells, B-cells and granulocytes were infected in vivo. To
      understand the mechanism of viral-cell interaction and the pathogenesis of HTLV-1
      using the mouse model, it is important to clarify the cellular tropism using a
      cell-free HTLV-1 transmission system. We employed a highly transmissible cell
      free HTLV-1 produced by a feline kidney cell line, c77, and studied the
      susceptibility of 9 kinds of mouse cell lines, EL4, RLm1, CTLL-2, J774.1, DA-1,
      Ba / F3, WEHI-3, NIH3T3 and B1, and two kinds of human cell lines, Molt-4 and
      Hut78. HTLV-1 proviral sequence was found by PCR in all 9 mouse cell lines as
      well as in 2 human cell lines and viral entry was blocked with sera from an HTLV
      1 carrier and an adult T-cell leukemia patient. Unexpectedly, mouse cell lines
      EL4 and RLm1 and human cell lines Molt-4 and Hut78 showed similar efficiency for
      viral entry. These results suggest a wide distribution of HTLV-1 receptor in
      mouse cells.

PMID- 11346464
TI  - Down-regulation in multiple human cancers of a novel gene, DMHC, from 17q25.1
      that encodes an integral membrane protein.
AB  - Frequent observations of allelic loss in chromosomal band 17q25.1 in a variety of
      human cancers have suggested that one or more tumor suppressor genes are present
      in that region. Moreover, a genetic locus for hereditary focal non-epidermolytic
      palmoplantar keratoderma, a condition associated with cancer of the esophagus
      (TOC; Tylosis with Oesophageal Cancer), lies in the same region. We screened cell
      lines derived from a variety of human cancers by reverse transcription-polymerase
      chain reaction (RT-PCR) to detect alterations in expression of genes within the
      region in question, by examining expressed sequence tags located there. These
      experiments identified an 1834-bp full-length cDNA encoding a novel, 441-amino
      acid integral membrane protein with seven putative transmembrane domains. This
      gene showed loss or extreme decrease of expression in 6 of 10 uterine cancer-cell
      lines, 2 of 11 hepatic cell carcinoma-cell lines, 2 of 7 lung cancer-cell lines,
      1 of 6 gastric cancer-cell lines, and 1 of 10 breast cancer-cell lines. (We named
      it DMHC ("down-regulated in multiple human cancers").) Our results suggest that
      loss of expression of DMHC at 17q25.1 may play an important role in development
      of variety of human cancers.

PMID- 11346465
TI  - A novel amplicon at 9p23 - 24 in squamous cell carcinoma of the esophagus that
      lies proximal to GASC1 and harbors NFIB.
AB  - The non-random amplification of DNA at 9p23 - 24 observed in various types of
      human cancers, including esophageal squamous cell carcinomas (ESCs), may reflect
      the locations of important tumor-associated genes. Our previous studies using ESC
      cell lines defined an amplicon in this region and identified a novel gene, GASC1,
      as a target of the amplification. Since different regions within the same
      chromosome arm are often involved in amplification in a syntenic or non-syntenic
      manner, we characterized the amplicon at 9p23 - 24 in 35 ESC cell lines (29 KYSE
      series and 6 YES series), and examined possible involvement of non-syntenic
      amplifications at 9p23 - 24 in 32 primary ESCs. Our results clearly indicated
      that two target regions for DNA amplification exist at 9p23 - 24; the major
      amplicon contains GASC1, and the minor one harbors a transcription factor, NFIB,
      centromeric to the GASC1 locus.

PMID- 11346466
TI  - Small GTP-binding protein, Rho, both increased and decreased cellular motility,
      activation of matrix metalloproteinase 2 and invasion of human osteosarcoma
      cells.
AB  - Rho, a member of the small GTP-binding proteins, and one of its downstream
      effectors ROCK (Rho-associated coiled-coil forming protein kinase) play an
      important role in the invasion of tumor cells. Lysophosphatidic acid (LPA)
      activates Rho and ROCK and promotes the organization of stress fibers and focal
      adhesions. However, the effect of LPA on tumor cell invasion is still
      controversial. In the present study, human osteosarcoma cells treated with a high
      concentration of LPA (high LPA) showed considerable formation of stress fibers
      and focal adhesions compared to the cells treated with a low concentration of LPA
      (low LPA). C3 (inhibitor of Rho) or Y27632 (an inhibitor of ROCK) inhibited the
      effects of LPA, indicating that LPA activates the Rho-ROCK pathway in the cells.
      In addition, Rho activation assay showed that the activation level of Rho can be
      altered by changing the concentration of LPA. Low LPA stimulated the motility and
      invasion of the cells, while high LPA reduced both. The disruption of
      extracellular matrix (ECM) by matrix metalloproteinase 2 (MMP2) is also critical
      for tumor cell invasion. MMP2 is activated by membranous type-1 MMP (MT1-MMP) and
      type-2 tissue inhibitor of MMP (TIMP2). High LPA suppressed the activation of
      MMP2 through down-regulation of MT1-MMP and TIMP2. C3 and Y27632 reversed the
      suppression of the activation of MMP2 and expression of MT1-MMP and TIMP2,
      suggesting the involvement of the Rho-ROCK pathway in ECM degradation. Tyrosine
      phosphorylation of focal adhesion kinase (FAK) was also required for the invasion
      of tumor cells to occur. Low LPA enhanced the tyrosine phosphorylation of FAK
      whereas high LPA reduced it. In conclusion, we suggest that Rho has a dual effect
      on the invasion of osteosarcoma cells by modulating the motility, the ability to
      degrade ECM and tyrosine phosphorylation of FAK.

PMID- 11346467
TI  - Enhanced vascular permeability in solid tumor involving peroxynitrite and matrix
      metalloproteinases.
AB  - Peroxynitrite (ONOO(-)), which is generated from nitric oxide (NO) and superoxide
      anion (O(2)(.-)) under pathological conditions, plays an important role in
      pathophysiological processes. Activation of matrix metalloproteinases (MMPs)
      contributes to tumor angiogenesis and metastasis. NO mediates the enhanced
      vascular permeability and retention (EPR) effect in solid tumors, and ONOO(
      )activates proMMP to MMP in vitro. In this study, we examined the role of ONOO(
      )in the EPR effect in solid tumors and normal tissues as related to MMP
      activation. Authentic ONOO(-), at 50 nmol or higher concentrations, induced the
      enhanced vascular permeability in normal dorsal skin of mice. ONOO(-)scavengers
      ebselen and uric acid significantly suppressed the EPR effect in mouse sarcoma
      180 (S-180) tumors. Indirect evidence for formation of ONOO(-)in S-180 and mouse
      colon adenocarcinoma (C-38) tumors included strong immunostaining for
      nitrotyrosine in the tumor tissue, predominantly surrounding the tumor vessels.
      MMP inhibitor BE16627B (66.6 mg / kg i.v., given 2 times) or SI-27 (10 mg / kg
      i.p., given 2 times) significantly suppressed the ONOO(-)-induced EPR effect in S
      180 tumors and in normal skin. Soybean trypsin inhibitor (Kunitz type), broad
      spectrum proteinase inhibitor ovomacroglobulin, and bradykinin receptor
      antagonist HOE 140 also significantly suppressed the ONOO(-)-induced EPR effect
      in normal skin tissues. These data suggest that ONOO(-)may be involved in and
      promote the EPR effect in tumors, which could be mediated partly through
      activation of MMPs and a subsequent proteinase cascade to generate potent
      vasoactive mediators such as bradykinin.

PMID- 11346468
TI  - Expression of multidrug resistance-related transporters in human breast
      carcinoma.
AB  - The expression levels of mRNA for multidrug resistance 1 (MDR1) gene, multidrug
      resistance protein 1 (MRP1), lung resistance-related protein (LRP) and breast
      cancer resistance protein (BCRP), which confer multidrug resistance in vitro,
      were examined in 43 untreated breast carcinoma patients, of whom 38 subsequently
      received doxorubicin-based chemotherapy after surgery, in order to elucidate the
      roles of these genes in drug resistance in vivo. The mRNA levels were determined
      using a semi-quantitative reverse-transcription polymerase chain reaction method
      in breast carcinoma tissues including at least 80% carcinoma cells. The
      expression level of BCRP gene was low and did not vary markedly in comparison
      with that of MDR1, MRP1 or LRP gene. The expressions of MDR1 and MRP1 genes were
      correlated with each other, but the expression of BCRP or LRP gene did not
      correlate with that of other genes. These four gene expressions were independent
      of age, TNM categories and the status of progesterone or estrogen receptor. The
      expression levels of these four genes were not related to the relapse or
      prognosis of the 38 patients treated with doxorubicin-based chemotherapy. P
      glycoprotein (P-gp) / MDR1, MRP1 and LRP may play more important roles than BCRP
      in chemotherapy of human breast carcinoma.

PMID- 11346469
TI  - Chitosan induces apoptosis via caspase-3 activation in bladder tumor cells.
AB  - Recently, because of its low toxicity and biological effects, chitosan has been
      widely used in the medical and pharmaceutical fields, e.g., for nasal or oral
      delivery of peptide or polar drug delivery. Here, we report a growth-inhibitory
      effect of chitosan on tumor cells. The growth inhibition was examined by WST-1
      colorimetric assay and cell counting. We also observed DNA fragmentation, which
      is characteristic of apoptosis, and elevated caspase-3-like activity in chitosan
      treated cancer cells. The findings suggest that chitosan may have potential value
      in cancer therapy.

PMID- 11346470
TI  - Co-transduction of Apaf-1 and caspase-9 augments etoposide-induced apoptosis in U
      373MG glioma cells.
AB  - Several apoptosis-related genes have been reported to be involved in chemotherapy
      induced apoptosis in cancers. An assessment of the relationship between
      expression of those genes and the degree of chemotherapy-induced apoptosis may be
      useful in improving the efficacy of cancer therapy. We transduced Apaf-1
      (apoptotic protease-activating factor-1) and caspase-9 into U-373MG glioma cells
      using adenovirus (Adv) vectors in the presence of etoposide and evaluated the
      degree of apoptosis. The degree of apoptosis in etoposide-treated U-373MG cells
      infected with Adv for Apaf-1 (Adv-APAF1) was higher (27%) than that in cells
      infected with control Adv (14%), that in cells infected with Adv for caspase-9
      (Adv-Casp9) was higher (34%) than that in cells infected with Adv-APAF1, and that
      in cells infected with both Adv-APAF1 and Adv-Casp9 was the highest (41%).
      Treatment with etoposide increased expression of p53 and decreased expression of
      Bcl-X(L) in U-373MG cells which harbored mutant p53. These results indicate that
      the expression of Apaf-1 and caspase-9 may be important determinants in
      predicting the sensitivity of cancers to chemotherapy. Adv-mediated co
      transduction of Apaf-1 and caspase-9 should render cancer cells highly sensitive
      to chemotherapy.

PMID- 11346471
TI  - Contribution of caspase-3 differs by p53 status in apoptosis induced by X
      irradiation.
AB  - We investigated the effect of p53 status on involvement of caspase-3 activation
      in cell death induced by X-irradiation, using rat embryonic fibroblasts (REFs)
      transduced with a temperature-sensitive mutant (mt) p53 gene. Cells with wild
      type (wt) p53 showed greater resistance to X-irradiation than cells with mt p53.
      In cells with wt p53, X-irradiation-induced apoptosis was not inhibited by the
      caspase-3 inhibitor acetyl-L-aspartyl-L-methionyl-L-glutaminyl-L-aspartyl
      aldehyde (Ac-DMQD-CHO) and caspase-3 activity was not elevated following X
      irradiation, although induction of p53 and p21 / WAF-1 protein was observed. In
      contrast, irradiated cells with mt p53 showed 89% inhibition of cell death with
      Ac-DMQD-CHO and 98% inhibition with the antioxidant N-acetyl-L-cysteine (NAC). In
      cells with mt p53, caspase-3 activity was increased approximately 5 times beyond
      baseline activity at 24 h after irradiation. This increase was almost completely
      inhibited by NAC. However, inhibition of caspase-3 by Ac-DMQD-CHO failed to
      decrease production of reactive oxygen species by cells with mt p53. Differential
      involvement of caspase-3 is a reason for differences in sensitivity to X
      irradiation in cells with different p53 status. Caspase-3 activation appears to
      occur downstream from generation of reactive oxygen species occurring
      independently of wt p53 during X-irradiation-induced cell death.

PMID- 11346472
TI  - An evaluation of the first year's experience with a low-cost telemedicine link in
      Bangladesh.
AB  - In July 1999, the Swinfen Charitable Trust in the UK established a telemedicine
      link in Bangladesh, between the Centre for the Rehabilitation of the Paralysed
      (CRP) in Dhaka and medical consultants abroad. This low-cost telemedicine system
      used a digital camera to capture still images, which were then transmitted by
      email. During the first 12 months, 27 telemedicine referrals were made. The
      following specialties were consulted: neurology (44%), orthopaedics (40%),
      rheumatology (8%), nephrology (4%) and paediatrics (4%). Initial email replies
      were received at the CRP within a day of referral in 70% of cases and within thee
      days in 100%, which shows that store-and-forward telemedicine can be both fast
      and reliable. Telemedicine consultation was complete within three days in 14
      cases (52%) and within three weeks in 24 cases (89%). Referral was judged to be
      beneficial in 24 cases (89%), the benefits including establishment of the
      diagnosis, the provision of reassurance to the patient and referring doctor, and
      a change of management. Four patients (15% of the total) and their families were
      spared the considerable expense and unnecessary stress of travelling abroad for a
      second opinion, and the savings from this alone outweighed the set-up and running
      costs in Bangladesh. The latter are limited to an email account with an Internet
      service provider and the local-rate telephone call charges from the CRP. This
      successful telemedicine system is a model for further telemedicine projects in
      the developing world.

PMID- 11346473
TI  - Factors affecting the use of a telephone-based intervention for caregivers of
      people with Alzheimer's disease.
AB  - We investigated the usefulness of a computer-mediated interactive voice response
      (IVR) system integrated with voicemail to help family caregivers manage
      disruptive behaviours in people with Alzheimer's disease. The randomization
      procedure resulted in 49 caregivers being assigned to the intervention group and
      51 to the control group. Using their ordinary telephone, the caregivers were
      linked to the four components of the IVR system: monitoring and counselling, an
      in-home support group, 'ask the expert', and a respite conversation. During an 18
      month study, total system usage amounted to 55 min per user (SD 78, range 1-318).
      Half the participants used the system for at least 22 min, and 25% for at least
      70 min. Participants made between one and 45 calls over the study period,
      averaging 11 calls (SD 12). Approximately half of the intervention group used the
      system regularly for two or more months. These 'adopters' were significantly
      older, more highly educated and reported a greater sense of management of the
      situation than 'non-adopters'. Adopters were much more likely than non-adopters
      to have been rated as highly proficient by the trainer following the technology
      training session. The IVR approach appealed to a subset of users. However, the
      overall preference was for human interaction.

PMID- 11346475
TI  - Telepsychiatry as a routine service--the perspective of the patient.
AB  - Patient perspectives were examined as part of an assessment of a routine
      telepsychiatry service in rural Alberta. Information was gathered through self
      report questionnaires and telephone interviews. Of 379 questionnaires distributed
      to patients, 230 (61%) were returned. Of the patients who completed
      questionnaires, 89% reported being satisfied with the service and 96-99% were
      satisfied with the equipment and the room. Twenty-nine of 31 patients who were
      interviewed by telephone preferred telepsychiatry to waiting for a consultation,
      were willing to use the service again and would recommend telepsychiatry to a
      friend. While 25 of these 31 patients preferred telepsychiatry to travelling to a
      consultation, 15 indicated that they would prefer a face-to-face interview to
      telepsychiatry and a further seven were unsure. Twenty-three of the 31 patients
      interviewed would have had to miss time from work or pay for child care in order
      to travel to a conventional psychiatric consultation. The availability of
      telepsychiatry led to an estimated cost saving of $210 per consultation for
      patients who would otherwise have had to travel. From the patient's perspective,
      telepsychiatry was an acceptable technique in the management of mental health
      difficulties that both increased access to services and produced cost savings.

PMID- 11346474
TI  - Neurological teleconsultation for general practitioners.
AB  - A neurology teleconsulting network was implemented between a university hospital
      in Lisbon and five nearby health centres. PCs equipped for videoconferencing were
      installed, connected by ISDN lines at 128 kbit/s. Fifty-three general
      practitioners (GPs) were surveyed. The survey showed that the GPs had
      difficulties in using computers, but they had definite intentions to use
      teleconsultation for neurology cases and 83% of the respondents stated that they
      would probably use the technique. During the study, 90 neurology
      teleconsultations took place over 55 weeks. The average consultation rate was 1.6
      teleconsultations per week (SD 1.3, range 0-6). The conferences lasted 10-45 min.
      Longer teleconsultations were mainly due to technical difficulties in using
      computers on the part of users with a low level of computer literacy. The
      patients were 42 males and 46 females, with a mean age of 38 years (SD 20, range
      1-84); two patients were discussed twice. The benefits consisted mainly of advice
      on patient medication, diagnosis and the prevention of unnecessary specialist
      consultations or laboratory examinations. Doctor-doctor teleconsultation allows
      the rapid resolution of queries which otherwise cause stress to patients and
      increase the cost and complexity of care.

PMID- 11346476
TI  - What do radiographers think about teleradiology in Japan?
AB  - In order to understand radiographers' views of teleradiology, we sent
      questionnaires to all radiographers in Hokkaido, Japan. Questions concerned the
      understanding of, interest in, need for and problems related to teleradiology. A
      total of 1275 radiographers responded to the survey (a response rate of 65%).
      Almost all had heard about teleradiology and about 60% of them were interested in
      it. However, fewer radiographers working in the central region than in other
      regions expected to be involved in teleradiology. If teleradiology were to be
      introduced, 60% of the respondents thought that it should be used for
      interpreting difficult cases and 30% for emergency cases. Half thought that the
      system should be managed and operated by the radiographer. Thirty-seven per cent
      of radiographers expected that there would be problems concerning the management
      of the system within one facility and between facilities, and 34% predicted
      problems with the installation costs.

PMID- 11346477
TI  - A cost study of teleconsultation for primary-care ophthalmology and dermatology.
AB  - Teleconsultations were performed between a health centre in a small Finnish town
      and a university hospital 55 km away. Telemedicine consultations were carried out
      with a total of 42 patients suffering from various eye and skin disorders. We
      evaluated the costs of the teleconsultations in the health centre and the
      conventional alternative of the patient travelling to the hospital. The cost of
      conventional consultations, which was not affected by the patient workload, was
      EU126 per patient for ophthalmology and EU143 per patient for dermatology. The
      cost of the teleconsultations per patient decreased as the number of patients
      increased. There were cost savings in relation to teleconsultations when the
      annual numbers of patients were more than 110 in ophthalmology and 92 in
      dermatology. Benefits and savings achieved through teleconsultations mainly
      consisted of reduced transportation costs and reduced paperwork both at the
      health centre and at the university hospital, as well as time savings for the
      patient. Another important benefit was improved medical education. The present
      study shows that teleconsultations can be performed in a cost-effective way in a
      relatively small health centre.

PMID- 11346478
TI  - Telemedicine for the delivery of professional development for health, education
      and welfare professionals in two remote mining towns.
AB  - Over a two-year period, telemedicine was used to deliver training and development
      services for health, education and welfare staff in two remote towns in South
      Australia - Roxby Downs and Coober Pedy. Both are mining towns but they have
      different profiles in terms of the community's mental health needs. The services
      were provided by the Child and Adolescent Mental Health Services (CAMHS) from the
      Women's and Children's Hospital in Adelaide, South Australia. The media used were
      videoconferencing, telephone, video-tapes, the Internet and printed material.
      During 1998-9, professional staff in the two locations participated in structured
      videoconferencing seminars that addressed important mental health topics, chosen
      in response to surveys of the needs of the participants. The videoconferencing
      sessions were sometimes used to discuss specific patient cases. Each remote town
      was also supported via videoconferencing by a nominated office of the CAMHS:
      Roxby Downs by the suburban office at Port Adelaide and Coober Pedy by the office
      in the industrial town of Port Pirie. This customized support was an important
      factor in the success of the professional development network.

PMID- 11346479
TI  - Teleradiology and teledermatology in Finnish military medicine.

PMID- 11346480
TI  - Medical net instruments: a new generation in telemedicine.

PMID- 11346481
TI  - Safety assessment of propyl paraben: a review of the published literature.
AB  - Propyl paraben (CAS no. 94-13-3) is a stable, non-volatile compound used as an
      antimicrobial preservative in foods, drugs and cosmetics for over 50 years. It is
      an ester of p-hydroxybenzoate. Propyl paraben is readily absorbed via the
      gastrointestinal tract and dermis. It is hydrolyzed to p-hydroxybenzoic acid,
      conjugated and the conjugates are rapidly excreted in the urine. There is no
      evidence of accumulation. Acute toxicity studies in animals indicate that propyl
      paraben is relatively non-toxic by both oral and parenteral routes, although it
      is mildly irritating to the skin. Following chronic administration, no-observed
      effect levels (NOEL) as high as 1200-4000 mg/kg have been reported and a no
      observed-adverse-effect level (NOAEL) in the rat of 5500 mg/kg is posited. Propyl
      paraben is not carcinogenic, mutagenic or clastogenic. It is not cytogenic in
      vitro in the absence of carboxyesterase inhibitors. The mechanism of propyl
      paraben may be linked to mitochondrial failure dependent on induction of membrane
      permeability transition accompanied by the mitochondrial depolarization and
      depletion of cellular ATP through uncoupling of oxidative phosphorylation.
      Sensitization has occurred when medications containing parabens have been applied
      to damaged or broken skin. Parabens have been implicated in numerous cases of
      contact sensitivity associated with cutaneous exposure, but high concentrations
      of 5-15% in patch testing are needed to elicit reaction in susceptible
      individuals. Allergic reactions to ingested parabens have been reported, although
      rigorous evidence of the allergenicity of ingested paraben is lacking.

PMID- 11346482
TI  - Effects of a Brussels sprouts extract on oxidative DNA damage and metabolising
      enzymes in rat liver.
AB  - The apparent anticarcinogenic effect of cruciferous vegetables found in numerous
      epidemiological and experimental studies has been associated with their influence
      on phase I and phase II metabolising enzymes as well as on the antioxidant
      status. In the present study we investigated the effect of administration of a
      Brussels sprouts extract on the expression at the mRNA level and/or catalytic
      activity in rat liver of three phase I enzymes [cytochrome P450-1A2 (CYP1A2),
      2B1/2 (CYP2B1/2) and-2E1 (CYP2E1)] and two phase II enzyme [NADPH:quinone
      reductase (QR) and glutathione S-transferase pi 7 (GSTpi)], all previously
      suggested to be induced by vegetables. We also examined the activity and/or
      expression of several important antioxidant enzymes: glutathione peroxidase
      (GPx), catalase and gamma-glutamyl-cysteine synthetase (GCS) and the activity of
      the repair enzyme 8-oxoguanine DNA glycosylase (OGG1). QR, GPx and catalase
      activity was also assessed in the kidneys. In order to examine a possible effect
      of the Brussels sprouts related to oxidative stress, we measured oxidative DNA
      damage in terms of 7-hydro-8-oxo-2'-deoxyguanosine (8-oxodG) and lipid
      peroxidation in terms of malondialdehyde (MDA) formation in the liver. Oral
      administration of an aqueous Brussels sprouts extract for 4 days was found to
      induce the expression of GST 1.3-fold (P < 0.05) and the activity of QR 2.6-fold
      in rat liver (P < 0.05). No significant differences were seen in the expression
      of the phase I enzymes. No differences in antioxidant enzyme activity/expression
      or OGG1 activity were observed. In a second experiment, administration of the
      Brussels sprouts extract for 3 or 7 days was found to increase the level of 8
      oxodG in rat liver from 0.75 to 0.97 per 10(5) dG and from 0.81 to 0.97 per 10(5)
      dG, respectively (P < 0.05). No effects on MDA levels were found. The present
      results support the data obtained in several studies that consumption of
      cruciferous vegetables is capable of inducing various phase II enzyme systems.
      However, the observed increase in oxidative DNA damage raises the question of
      whether greatly increased ingestion of cruciferous vegetables is beneficial.

PMID- 11346483
TI  - Inhibition of cytochrome P450 isozymes by curcumins in vitro and in vivo.
AB  - To study the mechanism(s) of turmeric-mediated chemoprevention and to compare the
      chemopreventive efficacy of turmeric/curcumin(s) against benzo[a]pyrene (B(a)P)
      and 4-methylnitrosamino-1-(3-pyridyl)-1-butanone (NNK, a tobacco-specific
      carcinogen), the effects of turmeric/curcumin (C), demethoxycurcumin (dmC), bis
      demethoxycurcumin (bdmC) and phenyl and phenethyl-isothiocyanates (PITC and
      PEITC) on the dealkylation of ethoxyresorufin (ER), methoxyresorufin (MR) and
      pentoxyresorufin (PR) by rat liver microsomes (in vitro) were studied. These
      reactions are predominantly mediated by cytochrome P450 (CYP450) isozymes 1A1,
      1A2 and 2B1, respectively. In vitro incubation of rat liver microsomes with each
      of the compounds--C, dmC, bdmC, PITC and PEITC--showed a dose-dependent decrease
      in carbon monoxide binding to microsomes and also showed a dose-dependent
      inhibition of CYP 1A1, 1A2 and 2B1 activity, as judged by a decrease in formation
      of resorufin from respective biochemical probes used. Both the isothiocyanates
      inhibited activity of CYP 2B1 more readily than that of CYP 1A1/1A2.
      Significantly lower concentrations of curcumin(s) than isothiocyanates achieved
      50% inhibition of activity of CYP 1A1 and 1A2, while concentrations of C (4
      microM), bdmC (2.5 microM) required to inhibit CYP 2B1 were slightly higher than
      that of PEITC (1.3 microM), suggesting curcumin(s) to be effective inhibitors of
      CYP 2B1 as well. Pretreatment of rats with 1% turmeric through the diet resulted
      in a significant decrease in induction of B(a)P-induced CYP 1A1 and 1A2 and
      phenobarbitone (PB)-induced CYP 2B1 in liver, lung and stomach, although the
      extent of the decrease was different. These results suggest that
      turmeric/curcumin(s) as in the case of isothiocyanate, PEITC, are likely to
      inhibit activation of carcinogens metabolized by CYP450 isozymes, namely, CYP
      1A1, 1A2 and 2B1.

PMID- 11346484
TI  - Protective effects of coffee diterpenes against aflatoxin B1-induced
      genotoxicity: mechanisms in rat and human cells.
AB  - The coffee-specific diterpenes cafestol and kahweol (C + K) have been reported to
      be anticarcinogenic in several animal models. Proposed mechanisms involve a co
      ordinated modulation of several enzymes responsible for carcinogen
      detoxification, thus preventing reactive agents interacting with critical target
      sites. To address the human relevance of the chemoprotective effects of C + K
      against aflatoxin B(1) (AFB1) genotoxicity observed in rat liver, and to compare
      the mechanisms of protection involved in both species, animal and human hepatic
      in vitro test systems were applied. In rat primary hepatocytes, C + K reduced the
      expression of cytochrome P450 CYP 2C11 and CYP 3A2, the key enzymes responsible
      for AFB1 activation to the genotoxic metabolite aflatoxin B1-8,9 epoxide (AFBO).
      In addition, these diterpenes induced significantly GST Yc2, the most efficient
      rat GST subunit involved in AFBO detoxification. These effects of C + K resulted
      in a marked dose-dependent inhibition of AFB1-DNA binding in this rat in vitro
      culture system. Their relevance in humans was addressed using liver epithelial
      cell lines (THLE) stably transfected to express AFB1 metabolising cytochrome
      P450s. In these cells, C + K also produced a significant inhibition of AFB1-DNA
      adducts formation linked with an induction of the human glutathione S-transferase
      GST-mu. Altogether, these results suggest that C + K may have chemoprotective
      activity against AFB1 genotoxicity in both rats and humans.

PMID- 11346485
TI  - Hepatocarcinogenesis inhibition by caffeine in ACI rats treated with 2
      acetylaminofluorene.
AB  - The inhibitory effects of caffeine have been demonstrated on the development of
      various organs in animals. The purpose of the present study was to examine the
      inhibitory effect of caffeine on hepatocarcinogenesis and to determine the
      responsive dose of caffeine on hepatocarcinogenesis in young male ACI rats.
      Animals given a diet containing 2-acetylaminofluorene (2-AAF) for 12 weeks and
      then a basal diet and tap water containing caffeine for 18 weeks showed
      statistically significant decreases in the incidence, multiplicity (the number of
      hepatic tumors per rat) and histological grade compared with rats fed a diet
      containing carcinogen for 12 weeks followed by tap water alone. Dose-dependent
      inhibition of hepatocarcinogenesis by caffeine was also seen. The inhibitory
      effect of caffeine on hepatocarcinogenesis in rats was found when caffeine was
      administered during the initiation phase.

PMID- 11346486
TI  - Effects of organosulfur compounds from garlic oil on the antioxidation system in
      rat liver and red blood cells.
AB  - The modulation of garlic oil (GO) and three allyl compounds, diallyl sulfide
      (DAS), diallyl disulfide (DADS) and diallyl trisulfide (DATS), on the
      antioxidation system in rat livers and red blood cells was examined. Rats were
      orally administered GO (200 mg/kg body weight), DAS (20, 80 mg/kg body weight),
      DADS (80 mg/kg body weight) or DATS (70 mg/kg body weight) three times a week for
      6 weeks. Control rats received corn oil (2 ml/kg body weight) alone. GO, DADS and
      DATS treatment significantly increased the glutathione (GSH) content (48-84%) in
      red blood cells (P < 0.05). DATS displayed a greater enhancement than GO and DADS
      (P < 0.05). Hemolysis induced by tert-butyl hydroperoxide was not suppressed by
      GO or allyl compound treatment although higher GSH content was evident. Hepatic
      GSH was not influenced by garlic components. In rat livers, DADS and DATS
      significantly increased the activity of GSH reductase (46 and 54%, respectively)
      and of GSH S-transferase (GST) (63 and 103%, respectively), but decreased the GSH
      peroxidase activity (27 and 28%, respectively). In contrast, GSH reductase and
      GST activities in the DAS group, either 20 or 80 mg/kg body weight, were similar
      to the control group. A decrease of GSH peroxidase activity was observed in rats
      dosed with 80 mg/kg body weight (P < 0.05). An increase in GST activity and a
      decrease in GSH peroxidase activities were also noted in GO-treated rats (P <
      0.05). In red blood cells, three GSH-related antioxidant enzyme activities were
      not affected by garlic oil and its organosulfur components. Immunoblot assay
      showed that, accompanying the increase in hepatic GST activity, GO, DADS, DAS (80
      mg/kg body weight) and DATS increased the expression of GST Ya, Yb1 and Yc
      proteins. Results indicate that GO and three allyl compounds play a differential
      role in modulation of the GSH-related antioxidant system in rat livers and red
      blood cells.

PMID- 11346487
TI  - Hepatic and renal metallothionein induction by an oral equimolar dose of zinc,
      cadmium or mercury in mice.
AB  - The hepatic and the renal subcellular distribution of zinc, cadmium or mercury
      and induction of tissue metallothionein (MT) at 24, 48 and 72 h following an oral
      equimolar dose (15 micro;mol metal/kg) of zinc (II) chloride, cadmium (II)
      chloride or mercury (II) chloride in male albino mice were investigated. There
      was a moderate increase in hepatic and renal zinc levels mainly in their nuclear
      mitochondrial fraction (NMF) 24 h post zinc chloride administration.
      Subsequently, the hepatic zinc increased and the renal zinc declined with time.
      The zinc-induced hepatic MT level was maximum at 48 h, which decreased slightly
      thereafter, while there was no marked increase in renal MT level at any time
      interval. The cadmium was equally distributed in liver and kidney more in their
      supernatant cytosol fraction (SCF) than in their NMF at 24 h after a dose of
      cadmium chloride. The cadmium levels showed a decreasing trend in hepatic
      fractions and an increasing trend in renal fractions with time. The cadmium
      induced hepatic and renal MT were substantial at 24 h post cadmium
      administration, the former decreased thereafter while the latter enhanced at 48 h
      before declining. The accumulation of mercury in kidney was 1.5 times that in
      liver, which was localised more in their SCF than in their NMF at 24 h in
      response to a dose of mercuric chloride. The mercury levels of hepatic and renal
      subcellular fractions started declining after 24 h and at 72 h they were
      significantly lower. The induction of hepatic and renal MT was maximum at 24 h
      after mercuric chloride administration, which declined thereafter concomitant
      with the decrease in their mercury levels. However, the MT levels in both the
      organs remained considerably higher than in normal animals at 72 h post exposure.
      The results show that the accumulation of metal in liver and kidney follows the
      order: Hg > Cd > Zn and the induction of MT follows Hg > Cd > Zn in liver and Cd
      > Hg > Zn in kidney. The alterations in zinc and copper homeostasis were more
      marked in liver than in kidney and follows the order: Hg > Cd > Zn.

PMID- 11346488
TI  - Experimental subchronic mycotoxicoses in mice: individual and combined effects of
      dietary exposure to fumonisins and aflatoxin B1.
AB  - We have used a murine model of subchronic mycotoxicoses produced by ingestion of
      mycotoxins. The five groups of animals studied were fed for 30, 60 and 90 days,
      respectively, with commercial diet (CD), experimental control diet (ECD),
      experimental with fumonisin B1 diet (EFD) and experimental with mixtures of
      mycotoxins diet (EMD). The animals fed EFD and EMD showed a significant increase
      in feed consumption/day with respect to the animals fed ECD (P < 0.005 for both
      groups). The biochemical measurements showed significant differences at 90 days
      in those animals fed EAD exhibiting a marked decrease in the values of alkaline
      phosphatase (ALP) and cholesterol (P < 0.05), along with a significant increase
      in calcium (P < 0.01). Differences in the decrease of the parameters studied were
      observed in mice fed EFD for triglycerides, cholesterol and calcium (P < 0.05 for
      all of them). The activity of aspartate transaminase (AST) increased
      significantly in animals fed EMD (P < 0.01). The tissue specimens at 60 days
      showed lesions in the livers of the animals fed EAD and EFD. At 90 days, and in
      those fed EAD, EFD and EMD, the lesions were intensified in the liver at 60 days
      in 80, 90 and 100% of the animals, respectively.

PMID- 11346489
TI  - Differential responses of certain brain phosphoesterases to aluminium in dietary
      protein adequacy and inadequacy.
AB  - The aluminium-induced neurotoxic consequences include, among other factors,
      dephosphorylation, phosphorylation as well as hyperphosphorylation of specific
      macromolecules. Accordingly, activities of phosphoesterases were measured in
      different regions of rat brain, maintained with either adequate or inadequate
      protein diet, following aluminium exposure. Male Wistar rats weighing 80-100 g
      were treated with aluminium chloride at a dose of 15% of the LD50 for 4 weeks. In
      different regions of the brain of aluminium-exposed rats, significant variation
      in both phosphomonoesterase and phosphodiesterase activities have been recorded.
      These alterations were found to be varied when the rats were subjected to dietary
      protein insufficiency. These findings demonstrate the specificity of aluminium on
      different phosphoesterases. These regional variations may be attributed to the
      accumulated level of aluminium or may be due to cellular localization of these
      enzymes and linked to whether the enzymes are compartmentalized with different
      aluminium hydration species.

PMID- 11346490
TI  - Heavy metal contents in Egyptian meat and the role of detergent washing on their
      levels.
AB  - Pollution of the environment with heavy metals is a serious problem, which is
      recognized in most countries of the world. Metals accumulate in the liver, and
      particularly in the kidneys. The present study provides information about the
      concentrations of metals in animal organs from both rural and industrial areas.
      It was surprising that the Pb, Cd, Zn, Cu, Mn and Fe contents in muscle, liver,
      kidney, heart and spleen in industrial areas were higher than in the same organs
      of rural areas. Lead concentrations in bovine liver and kidney, in buffalo, elk,
      sheep and goat kidneys as well as Cd in elk liver and kidneys were higher in the
      present study than the recommended values. The effect of washing for bovine
      muscle, liver and kidney using tap water and other detergent solutions on the
      metals was studied. Washing by only tap water was less effective than the other
      detergent. The results indicate the efficient role of washing by acidic detergent
      in the reduction of Pb, Cd and Zn from naturally contaminated meat compared with
      neutral and alkaline detergent.

PMID- 11346491
TI  - Multigenerational evaluation of sodium fluoride in rats.
AB  - Since the mid 1940s, fluoride has been added to tap water in American communities
      in an effort to reduce the incidence of dental caries in the population. When the
      levels of fluoride in drinking water were tested and set, water was the only
      measurable source of fluoride for most communities. Now, adults and children
      ingest fluoride with foods and beverages prepared with fluoridated water, and
      they are exposed to fluoride-containing dental products. As a result, exposure to
      fluoride is greater than had been anticipated. In the early 1990s, the existing
      reproductive studies were reviewed in several reports and were considered to be
      inadequate to determine potential reproductive or developmental hazards. The
      effects of sodium fluoride ingestion at 0, 25, 100, 175 or 250 ppm in drinking
      water measured in rats throughout three generations are reported here. Feed and
      fluid consumption, body weights and clinical signs were recorded at regular
      intervals. Decreased fluid consumption observed at 175 and 250 ppm was attributed
      to decreased palatability and did not affect reproduction. No cumulative effects
      were observed in the three generations. Mating, fertility and survival indices
      were not affected. Organ-to-body-weight ratios and organ-to-brain weight ratios
      were not affected. Sodium fluoride up to 250 ppm did not affect reproduction in
      rats.

PMID- 11346492
TI  - Prevention of brick tea fluorosis in rats with low-fluoride brick tea on
      laboratory observation.
AB  - To test whether low-fluoride brick tea can prevent the occurrence of fluorosis,
      rats had access only to a specially prepared low-fluoride brick tea for 1 year.
      The daily fluoride intake, fluoride metabolism, tissue distribution and
      development of tooth fluorosis were observed at 4-monthly intervals, at the end
      of months 4, 8 and 12, respectively. Rats drinking ordinary brick tea (F- 503.5
      mg/kg) served as control. The daily intake of fluoride in the ordinary brick tea
      group was 0.3 mg, and this group developed dental fluorosis characterized as
      brown and white horizontal marks at the end of month 8, and white chalky dental
      fluorosis developed at the end of month 12. The total incidence was 75%. In
      contrast, the daily fluoride intake of the low-fluoride brick tea (F- 210 mg/kg)
      group was 0.19 mg, and this group did not develop any signs of dental fluorosis.
      Fluoride distribution was mainly retained in the bone tissue, and about half of
      the absorbed fluoride was excreted via urine and feces. The results suggest that
      this low-fluoride brick tea did not induce fluorosis in rats and can be used as
      an effective control measure for humans.

PMID- 11346493
TI  - Skin sensitisation, vehicle effects and the local lymph node assay.
AB  - Accurate risk assessment in allergic contact dermatitis is dependent on the
      successful prospective identification of chemicals which possess the ability to
      behave as skin sensitisers, followed by appropriate measurement of the relative
      ability to cause sensitisation; their potency. Tools for hazard identification
      have been available for many years; more recently, a novel approach to the
      quantitative assessment of potency--the derivation of EC3 values in the local
      lymph node assay (LLNA)--has been described. It must be recognised, however, that
      these evaluations of chemical sensitisers also may be affected by the vehicle
      matrix in which skin exposure occurs. In this article, our knowledge of this area
      is reviewed and potential mechanisms through which vehicle effects may occur are
      detailed. Using the LLNA as an example, it is demonstrated that the vehicle may
      have little impact on the accuracy of basic hazard identification; the data also
      therefore support the view that testing ingredients in specific product
      formulations is not warranted for hazard identification purposes. However, the
      effect on potency estimations is of greater significance. Although not all
      chemical allergens are affected similarly, for certain substances a greater than
      10-fold vehicle-dependent change in potency is observed. Such data are vital for
      accurate risk assessment. Unfortunately, it does not at present appear possible
      to predict notionally the effect of the vehicle matrix on skin sensitising
      potency without recourse to direct testing, for example by estimation of LLNA EC3
      data, which provides a valuable tool for this purpose.

PMID- 11346494
TI  - Green tea and the metabolism of 2-amino-3-methylimidazo.
AB  - The effects of green tea intake on the metabolism of 2-amino-3-methylimidazo[4,5
      f]quinoline (IQ) in the rat was studied. IQ belongs to a new class of mutagens
      and carcinogens, heterocyclic arylamines, formed during cooking through browning
      meats and fish, thus, in the food chain of most non-vegetarians. Ten adult male
      and female Fischer 344 rats were placed on a 2% solution of green tea and 10
      control rats were on water for 6 weeks. Then, animals were administered a single
      dose of 40 mg/kg body weight of [2-14C]IQ by oral gavage. Twenty-four hour urine
      samples were collected and metabolites were separated by HPLC and quantitated by
      scintillation counting. Two minor and three major metabolites were isolated,
      including, small quantities of IQ itself. The rats on tea showed significant
      differences (P < 0.05) in the recovery of the three major metabolites, namely, IQ
      sulfamate, IQ-5-O-sulfate, and IQ-5-O-glucuronide, respectively. Green tea,
      therefore, influences the manner in which the food carcinogen IQ is metabolized
      and excreted in urine. Formation of glucuronides, increased by green tea,
      represent a key means of detoxification of the heterocyclic amine, IQ.

PMID- 11346495
TI  - Exercise testing in the new millennium.
AB  - In the changing economic times, internists and family physicians are becoming the
      main performers of the standard exercise test. The education of those
      noncardiologists who wish to perform exercise testing is quite important. In the
      new millennium, the American College of Cardiology/American Heart Association
      evidence-based guidelines on exercise testing continue to have a large impact.
      Used for diagnosis or prognosis, exercise scores such as the Duke exercise score
      will be applied to each test. Increased computerization and the internet will
      bring inexpensive web-enabled devices for sophisticated exercise testing into the
      doctor's office and allow remote over-reading services.

PMID- 11346496
TI  - The physiology behind exercise testing.
AB  - Despite significant advances in related technologies, the exercise test remains a
      useful clinical tool. It can define the limits of performance in an athlete or
      the functional capabilities of the patient with heart disease. Although virtually
      all of the body's physiologic and metabolic systems interact in a coordinated
      fashion to perform a single bout of exhaustive exercise, a major burden falls on
      the cardiopulmonary system. A good understanding of the basic physiologic
      responses to acute exercise can assist the clinician in applying the information
      gained from the test. These responses are influenced by state of health and
      fitness, age, gender, type of exercise, exercise position, and the environment.
      This article provides an overview of the physiologic responses to acute exercise,
      and discusses the many factors that influence these responses.

PMID- 11346497
TI  - Performing the exercise test.
AB  - Exercise testing is useful in assessing physical fitness, determining functional
      capacity, diagnosing ischemic heart disease, defining the prognosis of ischemic
      heart disease, developing an exercise prescription, and guiding cardiac
      rehabilitation. This article outlines the current indications, contraindications,
      and special considerations for exercise testing. Specific protocols are discussed
      along with physician responsibilities for performing this procedure. A summary of
      current testing equipment is included.

PMID- 11346498
TI  - Exercise testing in special populations: athletes, women, and the elderly.
AB  - Exercise testing in special populations such as athletes, women, and the elderly
      requires additional considerations from the clinician. Different protocols, as
      well as special accommodations, may be necessary for performing the test.
      Symptomatic athletes may have a number of cardiac conditions that lead to
      ischemic changes on the exercise test. Asymptomatic athletes often use serial
      exercise testing to evaluate the efficacy of training programs. For women and the
      elderly, assessment of risk factors and evaluation of symptoms are important
      considerations before performing the exercise test. Negative exercise test
      findings suggest a low risk for future cardiovascular events. Positive exercise
      test findings must be interpreted in light of the individual's pre-test
      probability. Assessment of the needs of these patients allows the clinician to
      tailor the exercise test to produce useful information.

PMID- 11346499
TI  - A basic approach to the interpretation of the exercise test.
AB  - To interpret the exercise test, the following parameters need to be evaluated:
      the heart rate and blood pressure response, symptoms, dysrhythmias, aerobic
      capacity, and evidence for myocardial ischemia. When analyzing the ST segment for
      ischemia, the amount and type of ST depression and the time of onset and
      resolution are examined. The exercise test results are best used to determine a
      post-test probability that the patient has significant coronary disease, predict
      its severity, and provide a prognosis of the patient. The test allows primary
      care physicians to decide which patients with coronary artery disease can be
      safely managed medically and which high-risk patients need further evaluation and
      consideration for revascularization.

PMID- 11346500
TI  - Risk stratification in patients with chest pain.
AB  - This article reviews the role of exercise testing in the assessment of patients
      with suspected coronary disease. To accomplish this, four major topics are
      considered: the general concept of risk stratification; the estimation of
      outcomes using data from the initial evaluation of the patient; diagnostic
      assessment with the exercise test; and prognostic assessment with the exercise
      test. This review focuses on the standard treadmill exercise test.

PMID- 11346502
TI  - Using the exercise test to create the exercise prescription.
AB  - Exercise testing can provide valuable information to aid the primary care
      physician in developing a safe and effective exercise program for his or her
      patients. This review presents the most recent recommendations for the components
      of an exercise program as well as methods to accomplish appropriate prescription
      writing for the various subsets of individuals from the healthy patient to the
      patient with chronic disease. In addition, a plea is made for physicians to
      encourage all patients to engage in at least some kind of regular exercise
      activity in an attempt to counteract the increasingly sedentary lifestyles found
      in our culture.

PMID- 11346501
TI  - The exercise test as a component of the total fitness evaluation.
AB  - The meaning, development, and means of testing for physical fitness are
      described. Emphasis is placed on measurement of all components of health-related
      physical fitness, including cardiorespiratory fitness, body composition, muscular
      strength and endurance, and flexibility.

PMID- 11346503
TI  - The role of gas analysis with exercise testing.
AB  - Evaluation of exercise performance is an integral component of every medical
      history. Currently, it is accomplished by means of subjective history taking.
      Routine exercise testing adds very little information; however, the addition of
      gas analysis (or cardio pulmonary exercise [CPX] testing) provides the crucial
      objective assessment by analyzing breath-by-breath oxygen uptake, carbon dioxide
      production, and anaerobic threshold (AT). Cardiac and pulmonary causes can be
      reliably differentiated, e.g., cardiac patients cross AT and attain VO2max, use
      less than 50% of maximal voluntary ventilation (MVV) at peak exercise, and do not
      develop desaturation. Pulmonary patients, on the contrary, fail to cross AT or
      achieve VO2max, utilize more than 70% of MVV at peak exercise, and develop
      arterial desaturation. In the current cost-conscious health care system, CPX
      proves to be a better cost-effective test because it is objective and more
      directly targeted to the issues than the conventional exercise test. CPX provides
      an important link between the disease process and its effect on exercise
      performance, which is crucial to a comprehensive clinical evaluation, diagnosis,
      prognosis, exercise prescription, and follow-up after medical or surgical
      intervention in patients with various diseases causing cardiopulmonary
      dysfunction.

PMID- 11346504
TI  - The clinical use of imaging techniques with exercise testing.
AB  - The addition of nuclear imaging techniques to basic exercise electrocardiography
      (ECG) has provided significant diagnostic and prognostic information in the
      evaluation of patients with suspected coronary artery disease. During the last
      decade, new classes of isotopes (technetium-and rubidium-based perfusion agents)
      and refinements in single-photon emission computed tomography (SPECT) and
      positron emission tomography (PET) have become better accepted. These new studies
      have added to the diagnostic armamentarium available to physicians, but at
      considerable costs with an estimated 4.8 million procedures performed this year.
      Nuclear imaging techniques can assess myocardial blood flow (perfusion imaging)
      or function (ventriculography). Another imaging modality, stress
      echocardiography, has also achieved widespread acceptance with clinical
      guidelines for its use published in 1997. This review addresses these imaging
      techniques in diagnostic evaluation of the patient with suspected coronary artery
      disease.

PMID- 11346505
TI  - Exercise testing in special situations: ER, preoperative and disability
      evaluation.
AB  - In a number of medical centers, exercise testing has proven to be a safe and
      useful tool in the evaluation of patients presenting chest pain in an emergency
      room. At these centers, after a period of observation without evidence of acute
      myocardial infarction, exercise testing is done. If the exercise test result is
      normal, the patient is discharged from the emergency room, without being admitted
      to the hospital. Exercise testing is a well-accepted noninvasive method to
      evaluate at-risk patients being considered for elective noncardiac surgery.
      Exercise testing is frequently used to determine functional capacity during
      disability assessment.

PMID- 11346506
TI  - Use of stress-testing modalities after angioplasty or bypass.
AB  - The use of stress-testing modalities after angioplasty or bypass has been an area
      of discussion and research since the advent of percutaneous transluminal coronary
      angioplasty (PTCA) and coronary artery bypass grafting (CABG). Issues of when to
      do which test, and if any, in asymptomatic or symptomatic patients, are not
      resolved. Stress imaging ETT plays a larger role in this population, but task
      forces stop short of coming out with any frequency of testing. Cost-effective
      strategies have not been explored. This article attempts to summarize the results
      in the literature.

PMID- 11346507
TI  - Some common abnormal responses to exercise testing: what to do when you see them.
AB  - This article reviews the role of exercise testing in the assessment of patients
      with suspected coronary disease. To accomplish this, four major topics are
      considered: the general concept of risk stratification; the estimation of
      outcomes using data from the initial evaluation of the patient; diagnostic
      assessment with the exercise test; and prognostic assessment with the exercise
      test. This review focuses on the standard treadmill exercise test.

PMID- 11346509
TI  - "Or sodai gomi" and Academic Medicine.

PMID- 11346508
TI  - The ACGME is unable to address residents' overwork.

PMID- 11346511
TI  - The changing field of academic public health.

PMID- 11346512
TI  - A program to facilitate clinical research in an AHC: the first five years.
AB  - The authors describe the first five years, 1996-2000, of the Clinical Research
      Program (CRP) at the Massachusetts General Hospital (MGH). The CRP was
      established to improve the quality and increase the quantity of clinical research
      within the MGH, and has concentrated on three areas: translational research,
      clinical trials, and outcomes research/epidemiology. The authors describe the
      CRP's efforts and strategies in these areas in detail, and explain the nature of
      the workforce, training, resources, and other factors that the CRP has brought to
      bear in fostering the goals in each area. The CRP's organization is also
      described, focusing on its administrative core and five units (e.g., the
      Education Unit), each of which has a distinct function in fostering clinical
      research. The success of the CRP's work can be measured in several ways,
      including greatly increased revenues from clinical trials and a large jump in the
      numbers of registrants for CRP courses. The authors state that CRP-type programs
      are essential for academic health centers (AHCs) that wish to maintain a balanced
      portfolio in clinical investigation in the future. They believe that AHCs that
      can afford to should invest in fostering their unique ability to train clinical
      investigators and generate new therapies for the future.

PMID- 11346513
TI  - Why physicians are unprepared to treat patients who have alcohol- and drug
      related disorders.
AB  - Most primary care physicians do not feel competent to treat alcohol- and drug
      related disorders. Physicians generally do not like to work with patients with
      these disorders and do not find treating them rewarding. Despite large numbers of
      such patients, the diagnosis and treatment of alcohol- and drug-related disorders
      are generally considered peripheral to or outside medical matters and ultimately
      outside medical education. There is substantial evidence that physicians fail
      even to identify a large percentage of patients with these disorders. Essential
      role models are lacking for future physicians to develop the attitudes and
      training they need to adequately approach addiction as a treatable medical
      illness. Faculty development programs in addictive disorders are needed to
      overcome the stigma, poor attitudes, and deficient skills among physicians who
      provide education and leadership for medical students and residents. The lack of
      parity with other medical disorders gives reimbursement and education for
      addiction disorders low priority. Medical students and physicians can also be
      consumers and patients with addiction problems. Their attitudes and abilities to
      learn about alcohol- and drug-related disorders are impaired without
      interventions. Curricula lack sufficient instruction and experiences in addiction
      medicine throughout all years of medical education. Programs that have
      successfully changed students' attitudes and skills for treatment of addicted
      patients continue to be exceptional and limited in focus rather than the general
      practice in U.S. medical schools. The authors review the findings of the
      literature on these problems, discuss the barriers to educational reform, and
      propose recommendations for developing an effective medical school curriculum
      about alcohol- and drug-related disorders.

PMID- 11346514
TI  - What residents are not learning: observations in an NICU.
AB  - In light of the November 1999 report of the Institute of Medicine on medical
      errors as a leading cause of death and injury, and the July 2000 report of the
      Accreditation Council for Graduate Medical Education citing violations of work
      hour standards for residents and interns, there is a clear need for substantial
      changes in residency training. The author, a clinical bioethicist, uses his
      extended observations at a neonatal intensive care unit (NICU) of a major U.S.
      teaching hospital to outline specific concerns about residents' and interns'
      training, medical and otherwise, that create unnecessary hazards and other
      difficulties in the medical care of children. These concerns-which arise from
      constructive criticisms he makes of specific NICU procedures, methods,
      approaches, and policies-apply directly to training residents in several areas of
      medicine and more generally to all residents' training, and echo many of the
      issues stated in the reports mentioned above. The author maintains that a well
      rounded medical education, fostering not only clinical skills but others (e.g.,
      skills in teaching; in communication; in collaborating with nurses, social
      workers, and others; in working with families; in showing compassion; in dealing
      with confidentiality issues; in using common sense; in being the patient's
      advocate), is crucial for producing well-rounded physicians. He emphasizes that
      in order for such a well-rounded education to occur, the residency program-which
      in many cases means the attending physicians-must teach and model these varied
      skills and attitudes to their trainees.

PMID- 11346515
TI  - Origins of modern premedical education.
AB  - The author reviews the contributions of those individuals and major academic and
      professional organizations responsible for the development of the modern concepts
      of the premedical education of a physician. The late 19th century gave rise to
      scientifically-based medical education in U.S. medical education. It followed
      that this new emphasis, in medical schools, on laboratory investigation of
      disease processes demanded a sound introduction to the natural sciences by those
      who would be candidates for this type of challenging education. Starting with a
      vocal few, the message gradually was received throughout the country that a
      properly schooled physician must have the equivalent of a broad baccalaureate
      education in the natural sciences as well as in the traditional humanities. This
      essential was recognized by a small nucleus of individuals responsible for the
      creation of The Johns Hopkins University in 1876 and its school of medicine in
      1893; the group was led by the university's first president, Daniel Coit GILMAN:
      Almost simultaneously other established academic institutions incorporated
      similar changes and a new era began.

PMID- 11346516
TI  - Do biomedical researchers have a role in the future of medical education?

PMID- 11346517
TI  - Role models and the learning environment: essential elements in effective medical
      education.

PMID- 11346518
TI  - Medical education at the mid-century.

PMID- 11346521
TI  - Direct graduate medical education payments to teaching hospitals by Medicare:
      unexplained variation and public policy contradictions.
AB  - PURPOSE: To comprehensively examine both inter- and intrastate variations in
      Medicare's cost-rate structure for teaching hospitals and to assess the Medicare
      payment system for graduate medical education (GME), as presently configured, as
      an instrument to promote physician workforce reform, specifically sufficient
      public access to primary care physician services. METHOD: Using Public Use Files
      of hospital cost reports from the Health Care Financing Administration for fiscal
      year 1997, 648 hospitals that met inclusion criteria for moderate GME volume were
      identified. The average and range of direct costs of resident training were
      computed for these teaching hospitals to illustrate differences within and
      between the 45 states that had at least two teaching hospitals that qualified for
      comparison. The cost rate upon which direct medical education (DME) payments are
      based was then correlated with the percentage of a state's counties that were
      wholly designated primary care health personnel shortage areas (PCHPSAs) in 1997
      and with its primary care physician-to-population ratio, as determined from the
      Area Resource FILE: RESULTS: Variations in inter- and intrastate DME costs exist.
      In some states, the range in DME rates substantially exceeded the mean cost. DME
      funding policies are more generous toward teaching hospitals in states with
      greater primary care physician-to-population ratios and smaller proportions of
      counties wholly designated PCHPSAS: CONCLUSION: Inherent inequities in DME
      funding seriously undermine the current Medicare GME payment system's capacity to
      contribute to U.S. physician workforce reform and to improve access to care.
      There is actually a financial incentive to train residents in areas in which
      there is relatively less need for their services.

PMID- 11346522
TI  - Measuring the direct costs of graduate medical education training in Minnesota.
AB  - PURPOSE: To demonstrate the usefulness of self-reported cost-accounting data from
      the sponsors of training programs for estimating the direct costs of graduate
      medical education (GME). The study also assesses the relative contributions of
      resident, faculty, and administrative costs to primary care, surgery, and the
      combined programs of radiology, emergency medicine, anesthesiology, and pathology
      (REAP). METHOD: The data were the FY97 direct costs of clinical education
      reported to Minnesota's Department of Health by eight sponsors of 117 accredited
      medical education programs, representing 394 sites of training (both hospital-
      and community-based) and 2,084 full-time-equivalent trainees (both residents and
      fellows). Average costs of clinical training were calculated as residency,
      faculty, and administrative costs. Preliminary analysis showed average costs by
      type of training programs, comparing the cost components for surgery, primary
      care, and REAP. RESULTS: The average direct cost of clinical training in FY97 was
      $130,843. Faculty costs were 52%, resident costs were 26%, and administrative
      costs were 20% of the total. Primary care programs' average costs were lower than
      were those of either surgery or REAP programs, but proportionally they included
      more administrative costs. CONCLUSIONS: As policymakers assess government
      subsidies for GME, more detailed cost information will be required. Self-reported
      data are more cost-effective and efficient than are the more detailed and costly
      time-and-motion studies. This data-collection study also revealed that faculty
      costs, driven by faculty hours and base salaries, represent a higher proportion
      of direct costs of GME than studies have shown in the past.

PMID- 11346523
TI  - Why aren't there more women leaders in academic medicine? the views of clinical
      department chairs.
AB  - PURPOSE: A scarcity of women in leadership positions in academic medicine has
      persisted despite their increasing numbers in medical training. To understand the
      barriers confronting women and potential remedies, clinical department chairs
      with extensive leadership experience were interviewed. METHOD: In 1998-99, open
      ended interviews averaging 80 minutes in length were conducted with 34 chairs and
      two division chiefs in five specialties. Individuals were selected to achieve a
      balance for gender, geographic locale, longevity in their positions, and
      sponsorship and research intensity of their institutions. The interviews were
      audiotaped and fully transcribed, and the themes reported emerged from inductive
      analysis of the responses using standard qualitative techniques. RESULTS: The
      chairs' responses centered on the constraints of traditional gender roles,
      manifestations of sexism in the medical environment, and lack of effective
      mentors. Their strategies for addressing these barriers ranged from individual or
      one-on-one interventions (e.g., counseling, confronting instances of bias, and
      arranging for appropriate mentors) to institutional changes (e.g., extending
      tenure probationary periods, instituting mechanisms for responding to
      unprofessional behavior, establishing mentoring networks across the university).
      CONCLUSION: The chairs universally acknowledged the existence of barriers to the
      advancement of women and proposed a spectrum of approaches to address them.
      Individual interventions, while adapting faculty to requirements, also tend to
      preserve existing institutional arrangements, including those that may have
      adverse effects on all faculty. Departmental or school-level changes address
      these shortcomings and have a greater likelihood of achieving enduring impact.

PMID- 11346524
TI  - Self-reported competency ratings of graduates of a problem-based medical
      curriculum.
AB  - PURPOSE: To study the self-reports of professional competencies by graduates of a
      problem-based medical curriculum. METHOD: All graduates from a medical school and
      a faculty of health sciences with a problem-based curriculum were sent a
      questionnaire asking them to compare their own performances in 19 domains with
      those of colleagues trained at schools with conventional curricula. RESULTS:
      Overall, alumni of the medical school rated themselves as better than colleagues
      who were trained at schools with conventional curricula for cooperation skills,
      problem-solving skills, skills relevant to running meetings, and the ability to
      work independently. There was no difference for possession of general academic
      knowledge and writing reports or articles. The self-reported ratings of better
      competencies were maintained after correcting the data for self-overestimation.
      CONCLUSION: The problem-based medical curriculum appears to contribute to the
      development of professional competencies. Further study is needed, however, to
      control for the effect of selection bias and respondents' emotional commitment to
      their alma mater.

PMID- 11346525
TI  - "Practicing" medicine without risk: students' and educators' responses to high
      fidelity patient simulation.
AB  - PURPOSE: To understand the responses of medical students and educators to high
      fidelity patient simulation, a new technology allowing "practice without risk."
      METHOD: Pilot groups of students (n = 27) and educators (n = 33) were exposed to
      a simulator session, then surveyed with multiple-choice and open-ended questions.
      Open-ended comments were transcribed and coded. They were analyzed for recurring
      themes and tested for inter-rater agreement. An independent focus group
      subsequently performed higher-level thematic analysis. RESULTS: Overall, 85% of
      the students rated the session excellent and 85% of the educators rated it
      excellent or very good. Over 80% of both groups thought that simulator-based
      training should be required for all medical students. Analytic categories derived
      from written comments were: Overall Assessment (i.e., "generally good
      experience"); Process Descriptors (i.e., "very realistic"); Teaching Utility
      (i.e., "broad educational tool"); Pedagogic Efficacy (i.e., "promotes critical
      thinking"); and Goals for Future Use (i.e., "more practice sessions"). Thirty
      percent of students and 38% of educators were impressed by the realism of the
      simulator, and they (37% and 25%, respectively) identified the ability to
      "practice" medicine as the primary advantage of simulation. The focus group rated
      cost as the major current disadvantage (66%). CONCLUSIONS: Students' and
      educators' responses to high-fidelity patient simulation were very positive. The
      ability to practice without risk must be weighed against the cost of this new
      technology.

PMID- 11346526
TI  - Relationship of tutors' group-dynamics skills to their performance ratings in
      problem-based learning.
AB  - PURPOSE: A tutor's performance is often investigated as a stable teacher
      characteristic, isolated from the context in which the tutor functions. This
      study investigated the influence of a tutor's group-dynamics skills in
      differently functioning tutorial groups on performance ratings. METHOD: Students'
      ratings of tutors' performances collected from 75 tutorial groups at one school
      over four different academic years were compared with the independent variables,
      groups' cohesion scores and sponging scores (the degree to which some students
      let others do the work), and the intervening variable, tutors' group-dynamics
      skills. RESULTS: Tutors with strong group-dynamics skills were assigned mean
      tutor's-performance scores of 7.4 (SD = 0.8) and 8.2 (SD = 0.5), respectively, by
      groups scoring low and high on cohesion. Tutors with low group-dynamics skills
      were rated 7.0 (SD = 1.1) and 7.4 (SD = 1.1) by the same groups. The same pattern
      held for sponging scores. Tutors who had strong group-dynamics skills received
      mean tutor's-performance scores of 8.1 (SD = 0.6) and 7.4 (SD = 0.8),
      respectively, from groups with low and high sponging scores. Tutors with weak
      group-dynamics skills were scored 7.6 (SD = 1.0) and 6.9 (SD = 1.1) by the same
      groups. CONCLUSIONS: Tutors possessing group-dynamics skills were rated higher by
      students than were tutors who lacked these skills, irrespective of the quality of
      a tutorial group's performance. A tutor who evaluates tutorial-group function on
      a regular basis and makes appointments with students based on these evaluations
      is seen as performing better than a tutor who does not.

PMID- 11346527
TI  - Obstacles to residents' conducting research and predictors of publication.
AB  - Internal medicine residents at one school identified barriers to and predictors
      of publishing their research. Insufficient time was the key obstacle to
      completing research. Residents with previous research experience, senior
      residents, and men were more likely to publish.

PMID- 11346528
TI  - Applying practical preventive skills in a preclinical preceptorship.
AB  - Learning primary care medicine includes learning to apply practical, preventive
      medicine skills during everyday encounters with patients. The authors relate
      their experiences with implementing a voluntary, preventive diabetic foot-care
      program within the Texas Statewide Family Practice Preceptorship Program
      (TSFPPP). They explain the background of the TSFPPP and their rationale for
      introducing prevention and selecting diabetic foot care as a first preventive
      training module. The program's structure, educational materials, and evaluations
      are described. Of the 158 students and 88 preceptors who were exposed to the
      program, the authors received evaluations from 86 preceptors and 110 students.
      Students documented that they had screened and provided foot-care education to
      321 diabetic patients. On average, students saved their preceptors 5-10 minutes
      each time they examined a diabetic patient's feet or provided foot-care
      education. The students said that the wide variety of preceptors' practices, the
      time constraints placed upon the preceptors, and the preceptors' own guidelines
      for the voluntary preceptorship all posed challenges to completing the preventive
      activities. The preceptors reported that preclinical students could play an
      important preventive role in their practices; however, to get optimum results
      from a preventive module, it may be important for students and preceptors to
      determine which topics are introduced. Using the preceptor's suggestions, the
      authors are developing a smoking-cessation module.

PMID- 11346529
TI  - The longitudinal primary care clerkship at Harvard Medical School.
AB  - The primary care clerkship (PCC) at Harvard Medical School was established in
      1997. The goals are to provide students with longitudinal experiences with
      patients and to include modern themes in the curriculum: managing illness and
      clinical relationships over time; finding the best available answers to clinical
      questions; preventing illness and promoting health; dealing with clinical
      uncertainty; getting the best outcomes with available resources; working in a
      health care team; and sharing decision making with patients. The PCC, a required
      course in the clinical years, meets one afternoon a week for nine months.
      Students spend three afternoons per month in primary care practices, where they
      see three to five patients per session and follow at least one patient
      ("longitudinal patient") over time. Classroom sessions, in both large- and small
      group formats, promote a common educational philosophy and experience, and
      reinforce habits of problem-based learning established in the preclinical years.
      The students rated 74% of their preceptors excellent, especially praising their
      ability to facilitate and support good interpersonal relationships with patients,
      their ability to encourage students' independent evaluation of patients (as
      opposed to shadowing), and their enthusiasm for teaching. Students saw their
      longitudinal patients a mean of 4.8 times; 83% saw their patients at least three
      times. The PCC complements the curriculum of block clerkships in hospitals, and
      because the two are offered concurrently, students are required to come to terms
      with two substantially different cultures within medicine. Other medical schools
      are beginning to develop longitudinal clerkships to ensure that students have
      essential educational experiences that are difficult to achieve in block,
      hospital-based clerkships.

PMID- 11346531
TI  - An online summer course for prematriculation medical students.

PMID- 11346530
TI  - A primary care preceptorship for first-year medical students coordinated by an
      Area Health Education Center program: a six-year review.
AB  - In 1991, the University of Florida College of Medicine established a required
      primary care preceptorship coordinated by the Area Health Education Center (AHEC)
      Program for all students in the first semester of medical school. Six years'
      experience with this course, which is entirely community-based and taught by
      community physicians, provides evidence of the success of the preceptorship. Over
      the first six years, 97% of students and 92% of preceptors felt strongly that
      this was an appropriate and valuable experience for students in the first
      semester of medical school. All believed that the students were capable of
      interacting with patients in a meaningful fashion and that the course allowed
      students to gain confidence as health care providers. The course also reinforced
      the importance of the basic science curriculum and initiated the process of
      professional development by affirming students' decisions to pursue a career in
      medicine. The use of content analysis to further evaluate attitudes and behaviors
      indicated that the students were highly satisfied with their experience and were
      active participants in the preceptors' practices. Students' approach to patients
      as people, rather than cases, was positive, and increased from the first to the
      last day of the preceptorship. After six years, this preceptorship has been
      demonstrated to have a positive and meaningful impact on medical student
      education and development.

PMID- 11346532
TI  - The Scholars in Primary Care Program: an assured admission program.

PMID- 11346533
TI  - Using lessons from American Indian health professionals at a health science
      center.

PMID- 11346534
TI  - Applicants' perceptions of the formal faculty interview during residency
      recruitment.

PMID- 11346535
TI  - The Experience of Illness module for beginning medical students.

PMID- 11346536
TI  - Medical student learning groups.

PMID- 11346537
TI  - Developing a stage-appropriate professionalism curriculum.

PMID- 11346538
TI  - Enriching the White Coat Ceremony with a module on professional responsibilities.

PMID- 11346539
TI  - A longitudinal approach to teaching and assessing professional attitudes and
      behaviors in medical school.

PMID- 11346540
TI  - Use of the Emotional Quotient Inventory in medical education.

PMID- 11346541
TI  - A workshop to teach and evaluate medical students' altruism.

PMID- 11346542
TI  - Measuring the emotional intelligence of medical school matriculants.

PMID- 11346543
TI  - Addressing prejudice in medicine during a third-year family medicine clerkship.

PMID- 11346544
TI  - Communication skills in women's health care: helping students clarify values
      related to challenging topics in ob-gyn.

PMID- 11346545
TI  - Objective assessment and structured teaching of disability etiquette.

PMID- 11346546
TI  - Using the "Question of Scruples" game to teach managed care ethics to students.

PMID- 11346547
TI  - A year-long course for third-year students on ethics, professionalism, and
      communication.

PMID- 11346548
TI  - A course about culture and gender in the clinical setting for third-year
      students.

PMID- 11346549
TI  - Cultural immersion in a cultural competency curriculum.

PMID- 11346550
TI  - A pathway on serving multicultural and underserved populations.

PMID- 11346551
TI  - A one-month cultural competency rotation for pediatrics residents.

PMID- 11346552
TI  - A culture OSCE: teaching residents to bridge different worlds.

PMID- 11346553
TI  - Teaching pediatrics residents to communicate with patients across differences.

PMID- 11346554
TI  - An international health/tropical medicine elective.

PMID- 11346555
TI  - A one-day interclerkship on end-of-life care.

PMID- 11346556
TI  - Training in end-of-life care through interaction with dying patients.

PMID- 11346557
TI  - A longitudinal home hospice rotation for internal medicine residents.

PMID- 11346558
TI  - Integrating spirituality into the family medicine residency curriculum.

PMID- 11346559
TI  - A comprehensive approach to teaching smoking-cessation strategies.

PMID- 11346560
TI  - Student attitudes toward wellness, empathy, and spirituality in the curriculum.

PMID- 11346561
TI  - An integrated approach to a tobacco-dependence curriculum.

PMID- 11346562
TI  - Collaboration among four medicine specialties to develop a curriculum on
      preconception health.

PMID- 11346563
TI  - An interdisciplinary effort in nutrition education in medical school.

PMID- 11346565
TI  - The Berkeley Suitcase Clinic: homeless services by undergraduate and medical
      student teams.

PMID- 11346564
TI  - Teaching students about health care of the homeless.

PMID- 11346566
TI  - A fourth-year elective course in alternative medicine.

PMID- 11346567
TI  - Threading geriatrics content through a four-year curriculum.

PMID- 11346568
TI  - Nurturing students' interest in primary care research through summer training in
      meta-analysis.

PMID- 11346569
TI  - A "medical team" format for tutorial groups and cases.

PMID- 11346570
TI  - Analyzing power relationships to teach about domestic violence.

PMID- 11346571
TI  - A teaching module to prevent needle sticks and exposures to body fluid.

PMID- 11346572
TI  - Identification of factors that influence the likelihood of screening for domestic
      violence by medical students and residents.

PMID- 11346573
TI  - Use of autopsy cases for integrating and applying the first two years of medical
      education.

PMID- 11346574
TI  - An approach to clinical correlations that stimulates clinical problem-solving
      skills.

PMID- 11346575
TI  - A workshop for first-year medical students on communicating scientific
      information to patients.

PMID- 11346576
TI  - Online peer evaluation in basic pharmacology.

PMID- 11346577
TI  - Application of team learning in a medical physiology course.

PMID- 11346578
TI  - Using personal digital assistants in a family medicine clerkship.

PMID- 11346579
TI  - Teaching cardiovascular physiology using patient simulation.

PMID- 11346580
TI  - Depression curriculum for students in a primary care internal medicine clerkship.

PMID- 11346581
TI  - The longitudinal patient-centered experience.

PMID- 11346582
TI  - Melding the family medicine and general internal medicine rotations into an
      ambulatory clerkship.

PMID- 11346583
TI  - Using standardized patients to identify students needing extra training in
      interviewing skills.

PMID- 11346584
TI  - An interdisciplinary interclerkship in genetic testing and ethics.

PMID- 11346585
TI  - A competency-based approach to clinical evaluation of students in the emergency
      department.

PMID- 11346586
TI  - A learner-centered evidence-based medicine rotation in a family practice
      residency.

PMID- 11346587
TI  - Supporting residents' EBM research on faculty's outpatient case studies.

PMID- 11346588
TI  - The evolution of SUMsearch for teaching clinical informatics to third-year
      medical students.

PMID- 11346589
TI  - Skills base: a Web-based electronic learning portfolio for clinical skills.

PMID- 11346590
TI  - MEOW: a Web site to improve consistency and communication in clerkships.

PMID- 11346591
TI  - A Web-based database for sharing educational multimedia within and among medical
      schools.

PMID- 11346592
TI  - A national Web site for residents as teachers.

PMID- 11346593
TI  - The ECLectic module: experiential clinical learning within a self-directed
      curriculum.

PMID- 11346594
TI  - A Web-based curriculum to improve residents' education in outpatient medicine.

PMID- 11346595
TI  - Creating Web-based patient education to enhance students' experience in a PBL
      curriculum.

PMID- 11346596
TI  - Web-based case simulations for a primary care clerkship.

PMID- 11346597
TI  - A Web-based clinical curriculum on the cardiac exam.

PMID- 11346598
TI  - An active learning framework that delivers clinical education case studies on the
      Web.

PMID- 11346599
TI  - Collaborative planning of a Web-based learning resource for primary care
      education.

PMID- 11346600
TI  - An interactive, Web-based learning environment for pathophysiology.

PMID- 11346601
TI  - The use of medical students in developing Web-based curriculum applications.

PMID- 11346602
TI  - Web-based assessment for students' testing and self-monitoring.

PMID- 11346603
TI  - Use of Verbot technology to enhance classroom lecture.

PMID- 11346604
TI  - A "gold standard" for designing Web sites for clerkships' online syllabi.

PMID- 11346605
TI  - Using feedback from patients' families to teach anesthesia residents.

PMID- 11346606
TI  - A retreat on leadership skills for residents.

PMID- 11346607
TI  - Response to the effect of hospitalist systems on residency education: re
      incorporating medical subspecialists.

PMID- 11346608
TI  - Employing hospitalists to improve residents' inpatient learning.

PMID- 11346609
TI  - Using small-group workshops to improve surgical residents' technical skills.

PMID- 11346610
TI  - A rotation in population-based health for internal medicine residents.

PMID- 11346611
TI  - Case-based teaching of perioperative medicine.

PMID- 11346612
TI  - The role of problem-based learning in a new family practice residency curriculum.

PMID- 11346613
TI  - A workshop for first-year residents on discussing "code status" in hospitals.

PMID- 11346614
TI  - A comprehensive curriculum in managed care for residents.

PMID- 11346615
TI  - Child advocacy training for pediatrics residents.

PMID- 11346616
TI  - Education in quality of care in an internal medicine residency program.

PMID- 11346617
TI  - An integrated model for teaching psychiatry in the community.

PMID- 11346618
TI  - A multidisciplinary ambulatory curriculum for a third-year rotation.

PMID- 11346619
TI  - A community hospice rotation for medicine residents.

PMID- 11346620
TI  - Improving systems for preventive care via academic detailing by students.

PMID- 11346621
TI  - A senior ambulatory block for aspiring general internists.

PMID- 11346622
TI  - Using "learning logs" to track experiences with preceptors.

PMID- 11346623
TI  - The Students Follow Patients Program: students attending patients with chronic
      disease in their homes.

PMID- 11346624
TI  - A modular family medicine training program at the master's-degree level and
      taught at a distance.

PMID- 11346625
TI  - A rotation in chronic-care pediatrics with a focus on children and their families
      in the community.

PMID- 11346626
TI  - Resident pairing: a successful way to meet RRC requirements in the ambulatory
      setting.

PMID- 11346627
TI  - A telemedicine case conference to teach medical students in a pediatrics setting.

PMID- 11346628
TI  - Developing benchmarks to measure instructional quality for ambulatory education.

PMID- 11346629
TI  - A curriculum to teach residents to teach in the ambulatory setting.

PMID- 11346630
TI  - A teaching scholars program to improve faculty development.

PMID- 11346631
TI  - The primary care faculty leadership fellowship for family medicine.

PMID- 11346632
TI  - Using student focus groups to improve faculty performance.

PMID- 11346633
TI  - The administrative tutorial: a PBL workshop for faculty development fellows.

PMID- 11346634
TI  - Using students' perceptions of internal medicine teachers' professionalism.

PMID- 11346635
TI  - A program for peer teachers in undergraduate medical education.

PMID- 11346636
TI  - A cross-training program for internal medicine and gynecology.

PMID- 11346637
TI  - Using a brochure to recruit faculty to teach.

PMID- 11346638
TI  - Attenuation of adhesion-dependent signaling and cell spreading in transformed
      fibroblasts lacking protein tyrosine phosphatase-1B.
AB  - Previous biochemical evidence has yielded conflicting models for the role of
      protein tyrosine phosphatase-1B (PTP-1B) in the regulation of integrin signaling.
      Thus, to establish the physiological relevance for such a role, we employed a
      genetic approach by generating embryonic fibroblasts from PTP-1B knockout mice.
      Both primary fibroblasts and their derived cell lines were used in this study.
      Immortalization of wild-type primary cells with the SV40 Large T antigen resulted
      in a dramatic increase in the endogenous expression of PTP-1B, suggesting a role
      during transformation. Moreover, the absence of PTP-1B in the transformed cell
      lines led to a more pronounced effect on different pathways of fibronectin
      mediated signaling compared with the untransformed state. Specifically, p130(Cas)
      phosphorylation, Erk activation as well as cell spreading were delayed in PTP-1B
      deficient cells, compared with their wild-type counterparts. Interestingly, this
      attenuation in integrin-mediated events closely resembles that of Src-deficient
      fibroblasts. Indeed, PTP-1B deficient, transformed fibroblasts held in suspension
      do exhibit a hyperphosphorylation of the inhibitory site (Tyr-527) of Src,
      compared with their wild-type counterparts. These results establish PTP-1B as a
      positive physiological regulator of integrin signaling in transformed cells,
      acting upstream of Src Tyr-527 dephosphorylation that leads to several adhesion
      dependent events.

PMID- 11346639
TI  - Mutational and kinetic evaluation of conserved His-123 in dual specificity
      protein-tyrosine phosphatase vaccinia H1-related phosphatase: participation of
      Tyr-78 and Thr-73 residues in tuning the orientation of His-123.
AB  - Active-site cysteine strategically positioned in the P-loop of protein-tyrosine
      phosphatases has been suggested to be further stabilized by hydrogen bonding
      arrays radiating out from the P-loop to neighboring residues. In this work, we
      investigated the structural role of histidine array in HC(X)(5)RS motif of the
      vaccinia H1-related protein phosphatase (VHR), using site-directed mutagenesis in
      conjunction with an extensive kinetic analysis. Conserved His-123 was mutated
      along with neighboring residues Tyr-78 and Thr-73. The increased pK(a) values of
      active-site Cys-124 found in Y78F and T73A mutants (6.51 and 6.75, respectively)
      were comparable to those of H123A and H123F mutants. Kinetic evaluation of Y78F
      and T73A mutants further implicates that the mutations perturb the relative
      position of Cys-124 within the P-loop. These results imply that Tyr-78 and Thr-73
      make up an essential part of the His-123 array and structurally tune the Cys-124
      position. Tyr-78 of VHR turns out to be the invariant Tyr reported in several
      protein-tyrosine phosphatases by a structure-based sequence alignment. Therefore,
      orientation of the imidazole ring of His-123 by the invariant Tyr-78 is crucial
      for maintaining the proper position of Cys-124 in the P-loop.

PMID- 11346640
TI  - Protein transduction domain of HIV-1 Tat protein promotes efficient delivery of
      DNA into mammalian cells.
AB  - The plasma membrane of mammalian cells is one of the tight barriers against gene
      transfer by synthetic delivery systems. Various agents have been used to
      facilitate gene transfer by destabilizing the endosomal membrane under acidic
      conditions, but their utility is limited, especially for gene transfer in vivo.
      In this article, we report that the protein transduction domain of human
      immunodeficiency virus type 1 Tat protein (Tat peptide) greatly facilitates gene
      transfer via membrane destabilization. We constructed recombinant lambda phage
      particles displaying Tat peptide on their surfaces and carrying mammalian marker
      genes as part of their genomes (Tat-phage). We demonstrate that, when animal
      cells are briefly exposed to Tat-phage, significant expression of phage marker
      genes is induced with no harmful effects to the cells. In contrast, recombinant
      phage displaying other functional peptides, such as the integrin-binding domain
      or a nuclear localization signal, could not induce detectable marker gene
      expression. The expression of marker genes induced by Tat-phage is not affected
      by endosomotropic agents but is partially impaired by inhibitors of caveolae
      formation. These data suggest that Tat peptide will become a useful component of
      synthetic delivery vehicles that promote gene transfer independently of the
      classical endocytic pathway.

PMID- 11346641
TI  - O-helix mutant T664P of Thermus aquaticus DNA polymerase I: altered catalytic
      properties for incorporation of incorrect nucleotides but not correct
      nucleotides.
AB  - Previous studies indicate that the O-helix of Thermus aquaticus (Taq) DNA
      polymerase I (pol I) plays an important role in the replication fidelity of the
      enzyme. This study examines the role of Thr-664, which lies in the middle of the
      O-helix of Taq pol I. A mutant of Taq Pol I with a proline substitution of Thr
      664 (T664P) exhibits much lower replication fidelity than the wild type enzyme in
      a forward mutation assay. T664P produces base substitution, single-base deletion,
      and single-base insertion errors at 20-, 5, and 50-fold higher rates than wild
      type, respectively. In specific activity and steady-state kinetic experiments,
      T664P was catalytically robust for insertion of correct nucleotides. In contrast,
      it incorporated incorrect nucleotides 6.1- to 10-fold more efficiently than wild
      type at a template dC. Mismatched primer termini were extended by T664P 4.2- to
      9.5-fold more efficiently than wild type. These data imply that the O-helix with
      a proline at position 664 functions like wild type Taq pol I for correct
      nucleotide incorporations, but bends and enlarges the catalytic pocket of the
      enzyme and increases the rate of nucleotide misincorporation.

PMID- 11346642
TI  - Differential requirement for Rho family GTPases in an oncogenic insulin-like
      growth factor-I receptor-induced cell transformation.
AB  - Insulin-like growth factor I receptor (IGFR) plays an important role in cell
      growth and transformation. We dissected the downstream signaling pathways of an
      oncogenic variant of IGFR, Gag-IGFR, called NM1. Loss of function mutants of NM1,
      Phe-1136 and dS2, that retain kinase activity but are attenuated in their
      transforming ability were used to identify signaling pathways that are important
      for transformation of NIH 3T3 cells. MAPK, phospholipase C gamma, and Stat3 were
      activated to the same extent by NM1 and its two mutants, suggesting that
      activation of these pathways, individually or in combination, was not sufficient
      for NM1-induced cell transformation. The mutant dS2 has decreased IRS-1
      phosphorylation levels and IRS-1-associated phosphatidylinositol 3'-kinase
      activity, suggesting that this impairment may be in part responsible for the
      defectiveness of dS2. We show that Rho family members, RhoA, Rac1, and Cdc42 are
      activated by NM1, and this activation, particularly RhoA and Cdc42, is attenuated
      in both mutants of NM1. Dominant negative mutants of Rho, Rac, and Cdc42
      inhibited NM1-induced cell transformation, as measured by focus and colony
      forming ability. Dominant negative Rho most potently inhibited the focus forming
      activity, whereas Cdc42 was most effective in inhibiting the colony forming
      ability of NM1-expressing cells. Conversely, constitutively activated (ca) Rho is
      more effective than ca Rac or ca Cdc42 in rescuing the focus forming ability of
      the mutants. By contrast, ca Cdc42 is most effective in rescuing the colony
      forming ability of both mutants.

PMID- 11346643
TI  - Antagonism of inhalant and volatile anesthetic enhancement of glycine receptor
      function.
AB  - Recent studies suggest that alcohols, volatile anesthetics, and inhaled drugs of
      abuse, which enhance gamma-aminobutyric acid, type A, and glycine receptor
      activated ion channel function, may share common or overlapping molecular sites
      of action on these receptors. To investigate this possibility, these compounds
      were applied singly and in combination to wild-type glycine alpha(1) receptors
      expressed in Xenopus laevis oocytes. Data obtained from concentration-response
      curves of the volatile anesthetic enflurane constructed in the presence and
      absence of ethanol, chloroform, or toluene were consistent with competition for a
      common binding pocket on these receptors. A mutant glycine receptor, insensitive
      to the enhancing effects of ethanol but not anesthetics or inhalants,
      demonstrated antagonism of anesthetic and inhalant effects on this receptor.
      Although ethanol (25-200 mm) had no effect on its own in this receptor, it was
      able to inhibit reversibly the enhancing effect of enflurane, toluene, and
      chloroform in a concentration-dependent manner. These data suggest the existence
      of overlapping molecular sites of action for ethanol, inhalants, and volatile
      anesthetics on glycine receptors and illustrate the feasibility of
      pharmacological antagonism of the effects of volatile anesthetics.

PMID- 11346644
TI  - Direct cell adhesion to the angiopoietins mediated by integrins.
AB  - Genetic ablation of angiopoietin-1 (Ang-1) or of its cognate receptor, Tie2,
      disrupts angiogenesis in mouse embryos. The endothelial cells in growing blood
      vessels of Ang-1 knockout mice have a rounded appearance and are poorly
      associated with one another and their underlying basement membranes (Dumont, D.
      J., Gradwohl, G., Fong, G. H., Puri, M. C., Gertsenstein, M., Auerbach, A., and
      Breitman, M. L. (1994) Genes Dev. 8, 1897--1909; Sato, T. N., Tozawa, Y.,
      Deutsch, U., Wolburg-Buchholz, K., Fujiwara, Y., Gendron-Maguire, M., Gridley,
      T., Wolburg, H., Risau, W., and Qin, Y. (1995) Nature 376, 70--74; Suri, C.,
      Jones, P. F., Patan, S., Bartunkova, S., Maisonpierre, P. C., Davis, S., Sato, T.
      N., and Yancopoulos, G. D. (1996) Cell 87, 1171--1180). It is therefore possible
      that Ang-1 regulates endothelial cell adhesion. In this study we asked whether
      Ang-1 might act as a direct substrate for cell adhesion. Human umbilical vein
      endothelial cells (HUVECs) plated for a brief period on different substrates were
      found to adhere and spread well on Ang-1. Similar results were seen on
      angiopoietin-2 (Ang-2)-coated surfaces, although cells did not spread well on Ang
      2. Ang-1, but not Ang-2, supported HUVEC migration, and this was independent of
      growth factor activity. When the same experiments were done with fibroblasts that
      either lacked, or stably expressed, Tie2, results similar to those with HUVECs
      were seen, suggesting that adhesion to the angiopoietins was independent of Tie2
      and not limited to endothelial cells. Interestingly, when integrin-blocking
      agents were included in these assays, adhesion to either angiopoietin was
      significantly reduced. Moreover, Chinese hamster ovary-B2 cells lacking the
      alpha(5) integrin subunit did not adhere to Ang-1, but they did adhere to Ang-2.
      Stable expression of the human alpha(5) integrin subunit in these cells rescued
      adhesion to Ang-1 and promoted an increase in adhesion to Ang-2. We also found
      that Ang-1 and Ang-2 bind rather selectively to vitronectin. These results
      suggest that, beyond their role in modulating Tie2 signaling, Ang-1 and Ang-2 can
      directly support cell adhesion mediated by integrins.

PMID- 11346645
TI  - Molecular cloning and characterization of a novel dual specificity phosphatase,
      LMW-DSP2, that lacks the cdc25 homology domain.
AB  - A novel dual specificity phosphatase (DSP) designated LMW-DSP2 was cloned with a
      combination of reverse transcription-polymerase chain reaction and cDNA library
      screening strategies. The LMW-DSP2 open reading frame of 194 amino acids
      contained a single DSP catalytic domain but lacked the cdc25 homology domain,
      which is conserved in most known DSPs. Northern blot and reverse transcription
      polymerase chain reaction analyses revealed that LMW-DSP2 was specifically
      expressed in testis. Recombinant LMW-DSP2 protein exhibited phosphatase activity
      toward an artificial low molecular weight substrate para-nitrophenyl phosphate,
      and the activity was inhibited completely by sodium orthovanadate but not sodium
      fluoride, pyrophosphate, and okadaic acid. The substitution of critical amino
      acid residues, aspartic acid and cysteine, resulted in a dramatic reduction of
      phosphatase activity. Transient transfection of LMW-DSP2 in COS7 cells resulted
      in the expression of a 21-kDa protein, and the phosphatase was shown to be
      distributed in both the cytosol and the nucleus. LMW-DSP2 dephosphorylated and
      deactivated p38, to a higher extent, and stress-activated protein kinase (SAPK)/c
      Jun N-terminal kinase (JNK), but not extracellular signal-regulated kinase 1/2
      mitogen-activated protein kinases, in transfected COS7 cells and in vitro.
      Interestingly, mutation in a conserved docking motif of p38 and SAPK/JNK as well
      as in a cluster of aspartic acids of LMW-DSP2 did not affect the deactivation of
      the mitogen-activated protein kinases by LMW-DSP2. Furthermore, the binding
      between LMW-DSP2 and p38 and SAPK/JNK was also not disrupted by such mutations.
      Among the DSPs lacking the cdc25 homology domain, LMW-DSP2 is the first one that
      dephosphorylates and deactivates p38 and SAPK/JNK.

PMID- 11346646
TI  - Acute inhibition of hepatic glucose-6-phosphatase does not affect gluconeogenesis
      but directs gluconeogenic flux toward glycogen in fasted rats. A pharmacological
      study with the chlorogenic acid derivative S4048.
AB  - Effects of acute inhibition of glucose-6-phosphatase activity by the chlorogenic
      acid derivative S4048 on hepatic carbohydrate fluxes were examined in isolated
      rat hepatocytes and in vivo in rats. Fluxes were calculated using tracer dilution
      techniques and mass isotopomer distribution analysis in plasma glucose and
      urinary paracetamol-glucuronide after infusion of [U-(13)C]glucose, [2
      (13)C]glycerol, [1-(2)H]galactose, and paracetamol. In hepatocytes, glucose-6
      phosphate (Glc-6-P) content, net glycogen synthesis, and lactate production from
      glucose and dihydroxyacetone increased strongly in the presence of S4048 (10
      microm). In livers of S4048-treated rats (0.5 mg kg(-1)min(-)); 8 h) Glc-6-P
      content increased strongly (+440%), and massive glycogen accumulation (+1260%)
      was observed in periportal areas. Total glucose production was diminished by 50%.
      The gluconeogenic flux to Glc-6-P was unaffected (i.e. 33.3 +/- 2.0 versus 33.2
      +/- 2.9 micromol kg(-1)min(-1)in control and S4048-treated rats, respectively).
      Newly synthesized Glc-6-P was redistributed from glucose production (62 +/- 1
      versus 38 +/- 1%; p < 0.001) to glycogen synthesis (35 +/- 5% versus 65 +/- 5%; p
      < 0.005) by S4048. This was associated with a strong inhibition (-82%) of the
      flux through glucokinase and an increase (+83%) of the flux through glycogen
      synthase, while the flux through glycogen phosphorylase remained unaffected. In
      livers from S4048-treated rats, mRNA levels of genes encoding Glc-6-P hydrolase
      (approximately 9-fold), Glc-6-P translocase (approximately 4-fold), glycogen
      synthase (approximately 7-fold) and L-type pyruvate kinase (approximately 4-fold)
      were increased, whereas glucokinase expression was almost abolished. In
      accordance with unaltered gluconeogenic flux, expression of the gene encoding
      phosphoenolpyruvate carboxykinase was unaffected in the S4048-treated rats. Thus,
      acute inhibition of glucose-6-phosphatase activity by S4048 elicited 1) a
      repartitioning of newly synthesized Glc-6-P from glucose production into glycogen
      synthesis without affecting the gluconeogenic flux to Glc-6-P and 2) a cellular
      response aimed at maintaining cellular Glc-6-P homeostasis.

PMID- 11346647
TI  - Site-directed mutagenesis of ATP binding residues of biotin carboxylase. Insight
      into the mechanism of catalysis.
AB  - Acetyl-CoA carboxylase catalyzes the first committed step in fatty acid synthesis
      in all plants, animals, and bacteria. The Escherichia coli form is a multimeric
      protein complex consisting of three distinct and separate components: biotin
      carboxylase, carboxyltransferase, and the biotin carboxyl carrier protein. The
      biotin carboxylase component catalyzes the ATP-dependent carboxylation of biotin
      using bicarbonate as the carboxylate source and has a distinct architecture that
      is characteristic of the ATP-grasp superfamily of enzymes. Included in this
      superfamily are d-Ala d-Ala ligase, glutathione synthetase, carbamyl phosphate
      synthetase, N(5)-carboxyaminoimidazole ribonucleotide synthetase, and glycinamide
      ribonucleotide transformylase, all of which have known three-dimensional
      structures and contain a number of highly conserved residues between them. Four
      of these residues of biotin carboxylase, Lys-116, Lys-159, His-209, and Glu-276,
      were selected for site-directed mutagenesis studies based on their structural
      homology with conserved residues of other ATP-grasp enzymes. These mutants were
      subjected to kinetic analysis to characterize their roles in substrate binding
      and catalysis. In all four mutants, the K(m) value for ATP was significantly
      increased, implicating these residues in the binding of ATP. This result is
      consistent with the crystal structures of several other ATP-grasp enzymes, which
      have shown specific interactions between the corresponding homologous residues
      and cocrystallized ADP or nucleotide analogs. In addition, the maximal velocity
      of the reaction was significantly reduced (between 30- and 260-fold) in the 4
      mutants relative to wild type. The data suggest that the mutations have
      misaligned the reactants for optimal catalysis.

PMID- 11346648
TI  - Quantitative analysis of the hormone-induced hyperacetylation of histone H3
      associated with the steroidogenic acute regulatory protein gene promoter.
AB  - Transcriptional regulation of steroidogenic acute regulatory protein (StAR)
      determines adrenal and gonadal cell steroidogenesis. Chromatin
      immunoprecipitation assays were combined with quantitative real-time polymerase
      chain reaction to assess histone acetylation associated with the StAR promoter.
      MA-10 cells treated with 8-bromo-cAMP had increased acetylated histone H3
      associated with the proximal (but not distal) StAR promoter, nascent StAR
      transcripts, and progesterone production within 15 min, whereas StAR mRNA
      increased at 30 min. At 360 min, steroidogenesis remained elevated, but mRNA,
      nascent RNA, and StAR promoter-associated H3 acetylation all declined. StAR
      promoter-associated H4 acetylation was unchanged by 8-bromo-cAMP treatment of MA
      10 cells. In vivo analysis of macaque and human granulosa cells showed that
      luteinization was associated with increased StAR promoter-associated H3
      acetylation. We conclude that acetylation of H3 (but not H4) associated with the
      proximal promoter is associated with StAR gene transcription, that chromatin
      modification occurs in discrete regions of the promoter, that the initial
      steroidogenic response to 8-bromo-cAMP occurs prior to increased StAR mRNA
      accumulation, and that MA-10 cell StAR gene transcription and promoter-associated
      H3 acetylation are biphasic during a 6-h treatment period. The union of the
      chromatin immunoprecipitation assay with quantitative real-time polymerase chain
      reaction described and validated here should enhance the analysis of gene
      expression.

PMID- 11346649
TI  - Lipopolysaccharide-induced apoptosis of macrophages determines the up-regulation
      of concentrative nucleoside transporters Cnt1 and Cnt2 through tumor necrosis
      factor-alpha-dependent and -independent mechanisms.
AB  - In murine bone marrow macrophages, lipopolysaccharide (LPS) induces apoptosis
      through the autocrine production of tumor necrosis factor-alpha (TNF-alpha), as
      demonstrated by the fact that macrophages from TNF-alpha receptor I knock-out
      mice did not undergo early apoptosis. In these conditions LPS up-regulated the
      two concentrative high affinity nucleoside transporters here shown to be
      expressed in murine bone marrow macrophages, concentrative nucleoside transporter
      (CNT) 1 and 2, in a rapid manner that is nevertheless consistent with the de novo
      synthesis of carrier proteins. This effect was not dependent on the presence of
      macrophage colony-stimulating factor, although LPS blocked the macrophage colony
      stimulating factor-mediated up-regulation of the equilibrative nucleoside
      transport system es. TNF-alpha mimicked the regulatory response of nucleoside
      transporters triggered by LPS, but macrophages isolated from TNF-alpha receptor I
      knock-out mice similarly up-regulated nucleoside transport after LPS treatment.
      Although NO is produced by macrophages after LPS treatment, NO is not involved in
      these regulatory responses because LPS up-regulated CNT1 and CNT2 transport
      activity and expression in macrophages from inducible nitric oxide synthase and
      cationic amino acid transporter (CAT) 2 knock-out mice, both of which lack
      inducible nitric oxide synthesis. These data indicate that the early proapoptotic
      responses of macrophages, involving the up-regulation of CNT transporters, follow
      redundant regulatory pathways in which TNF-alpha-dependent- and -independent
      mechanisms are involved. These observations also support a role for CNT
      transporters in determining extracellular nucleoside availability and modulating
      macrophage apoptosis.

PMID- 11346650
TI  - Multiple mechanisms regulate subcellular localization of human CDC6.
AB  - CDC6 is a protein essential for DNA replication, the expression and abundance of
      which are cell cycle-regulated in Saccharomyces cerevisiae. We have demonstrated
      previously that the subcellular localization of the human CDC6 homolog, HsCDC6,
      is cell cycle-dependent: nuclear during G(1) phase and cytoplasmic during S
      phase. Here we demonstrate that endogenous HsCDC6 is phosphorylated during the
      G(1)/S transition. The N-terminal region contains putative cyclin-dependent
      kinase phosphorylation sites adjoining nuclear localization sequences (NLSs) and
      a cyclin-docking motif, whereas the C-terminal region contains a nuclear export
      signal (NES). In addition, we show that the observed regulated subcellular
      localization depends on phosphorylation status, NLS, and NES. When the four
      putative substrate sites (serines 45, 54, 74, and 106) for cyclin-dependent
      kinases are mutated to alanines, the resulting HsCDC6A4 protein is localized
      predominantly to the nucleus. This localization depends upon two functional NLSs,
      because expression of HsCDC6 containing mutations in the two putative NLSs
      results in predominantly cytoplasmic distribution. Furthermore, mutation of the
      four serines to phosphate-mimicking aspartates (HsCDC6D4) results in strictly
      cytoplasmic localization. This cytoplasmic localization depends upon the C
      terminal NES. Together these results demonstrate that HsCDC6 is phosphorylated at
      the G(1)/S phase of the cell cycle and that the phosphorylation status determines
      the subcellular localization.

PMID- 11346651
TI  - Identification of Significant residues for homoallylic substrate binding of
      Micrococcus luteus B-P 26 undecaprenyl diphosphate synthase.
AB  - The primary structure of cis-prenyltransferase is totally different from those of
      trans-prenyltransferases (Shimizu, N., Koyama, T., and Ogura, K. (1998) J. Biol.
      Chem. 272, 19476-19481). To better understand the molecular mechanism of
      enzymatic cis-prenyl chain elongation, we selected seven charged residues in the
      conserved Region V and two of Phe-Ser motif in Region III of undecaprenyl
      diphosphate synthase of Micrococcus luteus B-P 26 for substitutions by site
      directed mutagenesis and examined their effects on substrate binding and
      catalysis. Kinetic studies indicated that replacements of Arg-197 or Arg-203 with
      Ser, and Glu-216 with Gln resulted in 7-11-fold increases of Km values for
      isopentenyl diphosphate and 18-1200-fold decreases of kcat values compared with
      those of the wild-type enzyme. In addition, two mutants with respect to the Phe
      Ser motif in Region III, F73A and S74A, showed 16-32-fold larger Km values for
      isopentenyl diphosphate and 12-16-fold lower kcat values than those of the wild
      type. Furthermore, product analysis indicated that three mutants, F73A, S74A, and
      E216Q, yielded shorter chain prenyl diphosphates as their main products. These
      facts together with the protein structural analysis recently carried out
      (Fujihashi, M., Zhang, Y.-W., Higuchi, Y., Li, X.-Y., Koyama, T., and Miki, K.
      (2001) Proc. Natl. Acad. Sci. U. S. A. 98, 4337-4342) indicated that the
      diphosphate moiety of homoallylic substrate is electrostatically recognized by
      the three charged amino acids, Arg-197, Arg-203, and Glu-216, in Region V and the
      Phe-Ser motif in Region III, also indispensable for homoallylic substrate binding
      as well as catalytic function. It was suggested that the undecaprenyl diphosphate
      synthase takes a different mode for the binding of isopentenyl diphosphate from
      that of trans-prenyl chain elongating enzymes.

PMID- 11346652
TI  - Nuclear factor-kappa B-inducible death effector domain-containing protein
      suppresses tumor necrosis factor-mediated apoptosis by inhibiting caspase-8
      activity.
AB  - Activation of the transcription factor nuclear factor-kappa B (NF-kappa B) has
      been found to play an essential role in the inhibition of tumor necrosis factor
      (TNF)-mediated apoptosis. NF-kappa B regulates several antiapoptotic molecules
      including inhibitors of apoptosis, Bcl-2 family proteins (A1 and Bcl-X(L))(,) and
      IEX-IL. Here we report that the expression of a small death effector domain (DED)
      containing protein, NDED (NF-kappa B-inducible DED-containing protein), depends
      on the activation of NF-kappa B. The inhibition of NF-kappa B by I kappa B alpha,
      a natural inhibitor of NF-kappa B, suppressed NDED mRNA expression induced by
      TNF. The restoration of NDED in NF-kappa B null cells inhibited TNF-induced
      apoptosis. Intriguingly, unlike the caspase-8 inhibitor cellular FADD-like
      interleukin-1 beta converting enzyme-inhibitory protein (c-FLIP), NDED suppressed
      TNF-mediated apoptosis by inhibiting TNF-induced caspase-8 enzymatic activity but
      not the processing of caspase-8. Furthermore, NDED could not inhibit etoposide
      mediated apoptosis that is independent of caspase-8 activation. Our results
      provide the first demonstration that NF-kappa B transcriptionally induces the DED
      containing protein to suppress TNF-mediated apoptosis by inhibiting caspase-8
      activity, which offers new insight into the antiapoptotic mechanism of NF-kappa
      B.

PMID- 11346653
TI  - Phosphonate ester probes for proteolytic antibodies.
AB  - The reactivity of phosphonate ester probes with several available proteolytic
      antibody (Ab) fragments was characterized. Irreversible, active site-directed
      inhibition of the peptidase activity was evident. Stable phosphonate diester-Ab
      adducts were resolved by column chromatography and denaturing electrophoresis.
      Biotinylated phosphonate esters were applied for chemical capture of phage
      particles displaying Fv and light chain repertoires. Selected Ab fragments
      displayed enriched catalytic activity inhibitable by the selection reagent.
      Somewhat unexpectedly, a phosphonate monoester also formed stable adducts with
      the Abs. Improved catalytic activity of phage Abs selected by monoester binding
      was evident. Turnover values (kcat) for a selected Fv construct and a light chain
      against their preferred model peptide substrates were 0.5 and 0.2 min(-1),
      respectively, and the corresponding Michaelis-Menten constants (Km) were 10 and 8
      microm. The covalent reactivity of Abs with phosphonate esters suggests their
      ability to recapitulate the catalytic mechanism utilized by classical serine
      proteases.

PMID- 11346654
TI  - Regulation of cell growth by redox-mediated extracellular proteolysis of platelet
      derived growth factor receptor beta.
AB  - Redox-regulated processes are important elements in various cellular functions.
      Reducing agents, such as N-acetyl-l-cysteine (NAC), are known to regulate signal
      transduction and cell growth through their radical scavenging action. However,
      recent studies have shown that reactive oxygen species are not always involved in
      ligand-stimulated intracellular signaling. Here, we report a novel mechanism by
      which NAC blocks platelet-derived growth factor (PDGF)-induced signaling pathways
      in hepatic stellate cells, a fibrogenic player in the liver. Unlike in vascular
      smooth muscle cells, we found that reducing agents, including NAC, triggered
      extracellular proteolysis of PDGF receptor-beta, leading to desensitization of
      hepatic stellate cells toward PDGF-BB. This effect was mediated by secreted
      mature cathepsin B. In addition, type II transforming growth factor-beta receptor
      was also down-regulated. Furthermore, these events seemed to cause a dramatic
      improvement of rat liver fibrosis. These results indicated that redox processes
      impact the cell's response to growth factors by regulating the turnover of growth
      factor receptors and that "redox therapy" is promising for fibrosis-related
      disease.

PMID- 11346655
TI  - The Arabidopsis thaliana ABC protein superfamily, a complete inventory.
AB  - We describe the first complete inventory of ATP-binding cassette (ABC) proteins
      from a multicellular organism, the model plant Arabidopsis thaliana. By the
      application of several search criteria, Arabidopsis was found to contain a total
      of 129 open reading frames (ORFs) capable of encoding ABC proteins, of which 103
      possessed contiguous transmembrane spans and were identified as putative
      intrinsic membrane proteins. Fifty-two of the putative intrinsic membrane
      proteins contained at least two transmembrane domains (TMDs) and two nucleotide
      binding folds (NBFs) and could be classified as belonging to one of five
      subfamilies of full-molecule transporters. The other 51 putative membrane
      proteins, all of which were half-molecule transporters, fell into five
      subfamilies. Of the remaining ORFs identified, all of which encoded proteins
      lacking TMDs, 11 could be classified into three subfamilies. There were no
      obvious homologs in other organisms for 15 of the ORFs which encoded a
      heterogeneous group of non-intrinsic ABC proteins (NAPs). Unrooted phylogenetic
      analyses substantiated the subfamily designations. Notable features of the
      Arabidopsis ABC superfamily was the presence of a large yeast-like PDR subfamily,
      and the absence of genes encoding bona fide cystic fibrosis transmembrane
      conductance regulator (CFTR), sulfonylurea receptor (SUR), and heavy metal
      tolerance factor 1 (HMT1) homologs. Arabidopsis was unusual in its large
      allocation of ORFs (a minimum of 0.5%) to members of the ABC protein superfamily.

PMID- 11346656
TI  - Manic fringe and lunatic fringe modify different sites of the Notch2
      extracellular region, resulting in different signaling modulation.
AB  - Three mammalian fringe proteins are implicated in controlling Notch activation by
      Delta/Serrate/Lag2 ligands during tissue boundary formation. It was proved
      recently that they are glycosyltransferases that initiate elongation of O-linked
      fucose residues attached to epidermal growth factor-like sequence repeats in the
      extracellular domain of Notch molecules. Here we demonstrate the existence of
      functional diversity among the mammalian fringe proteins. Although both manic
      fringe (mFng) and lunatic fringe (lFng) decreased the binding of Jagged1 to
      Notch2 and not that of Delta1, the decrease by mFng was greater in degree than
      that by lFng. We also found that both fringe proteins reduced Jagged1-triggered
      Notch2 signaling, whereas neither affected Delta1-triggered Notch2 signaling.
      However, the decrease in Jagged1-triggered Notch2 signaling by mFng was again
      greater than that by lFng. Furthermore, we observed that each fringe protein
      acted on a different site of the extracellular region of Notch2. Taking these
      findings together, we propose that the difference in modulatory function of
      multiple fringe proteins may result from the distinct amino acid sequence
      specificity targeted by these glycosyltransferases.

PMID- 11346657
TI  - Functional domains of the ClpA and ClpX molecular chaperones identified by
      limited proteolysis and deletion analysis.
AB  - Escherichia coli ClpA and ClpX are ATP-dependent protein unfoldases that each
      interact with the protease, ClpP, to promote specific protein degradation. We
      have used limited proteolysis and deletion analysis to probe the conformations of
      ClpA and ClpX and their interactions with ClpP and substrates. ATP gamma S
      binding stabilized ClpA and ClpX such that that cleavage by lysylendopeptidase C
      occurred at only two sites. Both proteins were cleaved within in a loop preceding
      an alpha-helix-rich C-terminal domain. Although the loop varies in size and
      composition in Clp ATPases, cleavage occurred within and around a conserved
      triad, IG(F/L). Binding of ClpP blocked this cleavage, and prior cleavage at this
      site rendered both ClpA and ClpX defective in binding and activating ClpP,
      suggesting that this site is involved in interactions with ClpP. ClpA was also
      cut at a site near the junction of the two ATPase domains, whereas the second
      cleavage site in ClpX lay between its N-terminal and ATPase domains. ClpP did not
      block cleavage at these other sites. The N-terminal domain of ClpX dissociated
      upon cleavage, and the remaining ClpXDeltaN remained as a hexamer, associated
      with ClpP, and expressed ATPase, chaperone, and proteolytic activity. A truncated
      mutant of ClpA lacking its N-terminal 153 amino acids also formed a hexamer,
      associated with ClpP, and expressed these activities. We propose that the N
      terminal domains of ClpX and ClpA lie on the outside ring surface of the
      holoenzyme complexes where they contribute to substrate binding or perform a
      gating function affecting substrate access to other binding sites and that a loop
      on the opposite face of the ATPase rings stabilizes interactions with ClpP and is
      involved in promoting ClpP proteolytic activity.

PMID- 11346658
TI  - A novel brain-specific box C/D small nucleolar RNA processed from tandemly
      repeated introns of a noncoding RNA gene in rats.
AB  - Antisense box C/D small nucleolar RNAs (snoRNAs) guide the 2'-O-ribose
      methylations of eukaryotic rRNAs and small nuclear RNAs (snRNAs) through
      formation of a specific base pairing at each RNA methylation site. By analysis of
      a box C/D snoRNA cDNA library constructed from rat brain RNAs, we have identified
      a novel box C/D snoRNA, RBII-36, which is devoid of complementarity to rRNA or an
      snRNA and exhibits a brain-specific expression pattern. It is uniformly expressed
      in all major areas of adult rat brain (except for choroid plexus) and throughout
      rat brain ontogeny but exclusively detected in neurons in which it exhibits a
      nucleolar localization. In vertebrates, known methylation guide snoRNAs are
      intron-encoded and processed from transcripts of housekeeping genes. In contrast,
      RBII-36 snoRNA is intron-encoded in a gene preferentially expressed in the rat
      central nervous system and not in proliferating cells. Remarkably, this host
      gene, which encodes a previously reported noncoding RNA, Bsr, spans tandemly
      repeated 0.9-kilobase units including the snoRNA-containing intron. The novel
      brain-specific snoRNA appears to result not only from processing of the
      debranched lariat but also from endonucleolytic cleavages of unspliced Bsr RNA
      (i.e. an alternative splicing-independent pathway unreported so far for mammalian
      intronic snoRNAs). Sequences homologous to RBII-36 snoRNA were exclusively
      detected in the Rattus genus of rodents, suggesting a very recent origin of this
      brain-specific snoRNA.

PMID- 11346660
TI  - HIV integrase, a brief overview from chemistry to therapeutics.

PMID- 11346659
TI  - Site-specific phosphorylation and point mutations of telokin modulate its Ca2+
      desensitizing effect in smooth muscle.
AB  - Forskolin and 8-bromoguanosine 3'-5'-cyclic monophosphate (8-Br-cGMP) induce
      phosphorylation of Ser-13 of telokin and relaxation of smooth muscle at constant
      calcium. Comparison with the effect of wild type with aspartate (D; to mimic
      phosphorylation) and alanine (A; non-phosphorylatable) mutants of telokin showed
      that the S13D mutant was more effective than wild type in relaxing smooth muscle
      at constant calcium. The efficacy of the Ser-13A, S12A, and S12D mutants was not
      significantly different from that of wild-type telokin. The effect of neither
      S13D nor Ser-13A was affected by 8-Br-cGMP, whereas the effect of wild type,
      S12A, and S12D was enhanced by 8-Br-cGMP, indicating the specificity of Ser-13
      charge modification. Mutation of Ser-19 (a mitogen-activated protein kinase site)
      showed the S19A to be more effective than, and S19D to be not different from,
      wild-type telokin. The effect of both mutants was slightly enhanced by 8-Br-cGMP.
      A truncated (residues 1-142) form lacking the acidic C terminus had the same
      relaxant effect as wild-type telokin, whereas the C-terminal peptide (residues
      142-155) had no effect. We conclude that site-specific modification of the N
      terminus modulates the Ca2+ -desensitizing effect of telokin on force.

PMID- 11346661
TI  - Hypertension and type 2 diabetes comorbidity in adults in the United States: risk
      of overall and regional adiposity.
AB  - OBJECTIVE: To evaluate the impact of generalized, abdominal, and truncal fat
      deposits on the risk of hypertension and/or diabetes and to determine whether
      ethnic differences in these fat patterns are independently associated with
      increased risk for the hypertension-diabetes comorbidity (HDC). RESEARCH METHODS
      AND PROCEDURES: Data (n = 7075) from the Third U.S. National Health and Nutrition
      Examination Survey were used for this investigation. To assess risks of
      hypertension and/or diabetes that were due to different fat patterns, odds ratios
      of men and women with various cut-points of adiposities were compared with normal
      subjects in logistic regression models, adjusting for age, smoking, and alcohol
      intake. To evaluate the contribution of ethnic differences in obesity to the
      risks of HDC, we compared blacks and Hispanics with whites. RESULTS: Generalized
      and abdominal obesities were independently associated with increased risk of
      hypertension, diabetes and HDC in white, black, and Hispanic men and women. The
      risk of HDC due to generalized, truncal, and abdominal obesities tended to be
      higher in whites than blacks and Hispanics. In men, the contribution of black and
      Hispanic ethnicities to the increased risk of HDC due to the various obesity
      phenotypes was approximately 73% and approximately 61%, respectively. The
      corresponding values for black and Hispanic women were approximately 115% and
      approximately 125%, respectively. CONCLUSIONS: In addition to advocating
      behavioral lifestyles to curb the epidemic of obesity among at-risk populations
      in the United States, there is also the need for primary health care
      practitioners to craft their advice to the degree and type of obesity in these at
      risk groups.

PMID- 11346662
TI  - Comparison of regional fat distribution and health risk factors in middle-aged
      white and African American women: The Healthy Transitions Study.
AB  - OBJECTIVE: Both ethnicity and menopause appear to influence intra-abdominal fat
      distribution. This study evaluated intra-abdominal fat distribution and obesity
      related health risks in perimenopausal white and African American women. RESEARCH
      METHODS AND PROCEDURES: Baseline data from a longitudinal study of changes in
      body composition and energy balance during menopause are reported. Healthy women
      (55 African Americans and 103 whites) who were on no medication and had at least
      five menstrual cycles in the previous 6 months were recruited. Body composition
      was assessed by DXA, and visceral adipose tissue (VAT) and subcutaneous adipose
      tissue (SAT) were assessed by computed tomography scan. SAT was divided into deep
      and superficial layers demarcated by the fascia superficialis. RESULTS: African
      American women were slightly younger (46.7 +/- 0.2 vs. 47.7 +/- 0.2 years, p =
      0.002) and fatter (42.4% +/- 1.0% vs. 39.4% +/- 0.8% body fat, p = 0.02) than
      white women. In unadjusted data, African Americans had significantly more total
      abdominal fat and total, deep, and superficial SAT than whites. After adjustment
      for percent body fat and age, only total and superficial SAT remained
      significantly higher in African Americans. VAT, although slightly less in African
      American women, did not differ significantly by race. In multiple regression
      analysis, VAT was the strongest predictor of serum lipids, glucose, and insulin
      in women of both races, although superficial SAT was significantly associated
      with fasting glucose in whites. CONCLUSIONS: Middle-aged African American women
      have larger SAT depots, adjusted for total body fatness, but do not differ from
      white women with regard to VAT. The complexity of the relationship between
      abdominal fat and metabolic risk is increased by ethnic differences in such
      associations.

PMID- 11346663
TI  - Is body mass index a measure of adiposity in elderly women?
AB  - OBJECTIVE: To evaluate the accuracy of body mass index (BMI) as a predictor of
      body fat in elderly women. RESEARCH METHODS AND PROCEDURES: A total of 1423 women
      aged 67 +/- 5 (mean +/- SD, range: 60 to 88) years were consecutively enrolled
      into the study. Fat mass (FM) was measured using DXA. RESULTS: BMI explained
      72.9% of FM variance (p < 0.0001), with a root mean square error of estimate
      (RMSE) of 3.5 kg. After standardization of RMSE on the dependent variable as
      RMSE%, the prediction error equaled 15%. BMI explained 54.8% of FM% variance (p <
      0.0001), with an RMSE of 4.1%, corresponding to an RMSE% of 11%. DISCUSSION: The
      relatively high RMSE% of the FM and FM%-BMI associations caution against the use
      of BMI as an adiposity index in individual elderly women. However, an error
      corresponding to 11% of FM% may be accepted for population studies of body fat in
      elderly women.

PMID- 11346664
TI  - Self-reported body mass index and health-related quality of life: findings from
      the Behavioral Risk Factor Surveillance System.
AB  - OBJECTIVE: To examine the relationship between self-reported body mass index
      (BMI) and health-related quality of life in the general adult population in the
      United STATES: RESEARCH METHODS AND PROCEDURES: Using data from 109,076
      respondents in the 1996 Behavioral Risk Factor Surveillance System, we examined
      how self-reported BMI is associated with five health-related quality of life
      measures developed by the Centers for Disease Control and Prevention for
      population health surveillance. RESULTS: After adjusting for age, gender, race or
      ethnicity, educational attainment, employment status, smoking status, and
      physical activity status, participants with a self-reported BMI of <18.5 kg/m(2)
      and participants with a self-reported BMI of > or =30 kg/m(2) reported impaired
      quality of life. Compared with persons with a self-reported BMI of 18.5 to <25
      kg/m(2), odds ratios (ORs) of poor or fair self-rated health increased among
      persons with self-reported BMIs of <18.5 (1.57, 95% confidence interval [CI]:
      1.31 to 1.89), 25 to <30 kg/m(2) (1.12, 95% CI: 1.04 to 1.20), 30 to <35 kg/m(2)
      (1.65, 95% CI: 1.50 to 1.81), 35 to <40 kg/m(2) (2.58, 95% CI: 2.21 to 3.00), and
      > or =40 kg/m(2) (3.23, 95% CI: 2.63 to 3.95); ORs for reporting > or =14 days of
      poor physical health during the previous 30 days were 1.44 (95% CI: 1.21 to
      1.72), 1.04 (95% CI: 0.96 to 1.14), 1.32 (95% CI: 1.19 to 1.47), 1.80 (95% CI:
      1.52 to 2.13), and 2.37 (95% CI: 1.90 to 2.94), respectively; ORs for having > or
      =14 days of poor mental health during the previous 30 days were 1.18 (95% CI:
      0.97 to 1.42), 1.02 (95% CI: 0.95 to 1.11), 1.22 (95% CI: 1.10 to 1.36), 1.68
      (95% CI: 1.42 to 1.98), and 1.66 (95% CI: 1.32 to 2.09), respectively.
      DISCUSSION: In the largest study to date, low and increased self-reported BMI
      significantly impaired health-related quality of life. Particularly, deviations
      from normal BMI affected physical functioning more strongly than mental
      functioning.

PMID- 11346666
TI  - Body Morph Assessment: preliminary report on the development of a computerized
      measure of body image.
AB  - OBJECTIVE: To develop a prototype of the Body Morph Assessment (BMA), and to test
      the reliability and validity of this new measure of body image. The BMA is a
      realistic and relatively simple procedure that uses computer morphing for the
      assessment of body image. For the purposes of this preliminary study, a prototype
      of the BMA was developed for usage with white women ranging from very thin to
      obese. RESEARCH METHODS AND PROCEDURES: A total of 72 subjects participated in
      tests of reliability, content, and convergent validity of the BMA. RESULTS: The
      reliability and validity of the BMA was supported by the results of this study.
      In a test of convergent validity, the measures of current, ideal, and reasonable
      body size were positively correlated with their equivalents from a similar body
      image assessment procedure. In addition, reliability coefficients were found to
      be satisfactory for all variables. Participants found the human figural stimuli
      to be realistic. DISCUSSION: These preliminary findings support the reliability
      and validity of the BMA with white women. Given these positive findings, we plan
      to extend the procedure to males and to other racial and ethnic groups.

PMID- 11346665
TI  - Social, educational, and psychological correlates of weight status in
      adolescents.
AB  - OBJECTIVES: The purpose of this research was to examine the social, educational,
      and psychological correlates of weight status in an adolescent population. It was
      hypothesized that obese adolescents would differ on psychological, social, and
      educational variables compared with their non-overweight peers. RESEARCH METHODS
      AND PROCEDURES: In this cross-sectional study, a population-based sample of 4742
      male and 5201 female public school students in the 7th, 9th, and 11th grades
      responded anonymously to a classroom administered questionnaire. Body mass index
      was calculated from self-reported height and weight and categorized into four
      classes of weight status: underweight (<15th percentile), average weight (15th to
      85th percentile), overweight (>85th to 95th percentile), and obese (>95th
      percentile). The questionnaire also included questions about social experiences,
      psychological well-being, educational experiences, and future goals. Associations
      of weight status with social, psychological, and educational variables and future
      goals were explored. RESULTS: After adjustment for grade level, race, and
      parental socioeconomic status, obese girls, when compared with their average
      weight counterparts, were 1.63 (95% confidence interval [CI]: 1.16, 2.30) times
      less likely to hang out with friends in the last week, 1.49 (95% CI: 1.12, 1.98)
      times more likely to report serious emotional problems in the last year, 1.79
      (95% CI: 1.20, 2.65) times more likely to report hopelessness, and 1.73 (95% CI:
      1.21, 1.98) times more likely to report a suicide attempt in the last year. Obese
      girls were also 1.51 (95% CI: 1.09, 2.10) times more likely to report being held
      back a grade and 2.09 (95% CI: 1.35, 3.24) times more likely to consider
      themselves poor students compared with average weight girls. Compared with their
      average weight counterparts, obese boys were 1.91 (95% CI: 1.43, 2.54) times less
      likely to hang out with friends in the last week, 1.34 (95% CI: 1.06, 1.70) times
      more likely to feel that their friends do not care about them, 1.38 (95% CI:
      1.08, 1.76) times more likely to report having serious problems in the last year,
      1.46 (95% CI: 1.05, 0.03) times more likely to consider themselves poor students,
      and 2.18 (95% CI: 1.45, 3.30) times more likely to expect to quit school.
      Compared with average weight boys, underweight boys were 1.67 (95% CI: 1.30,
      2.13) times more likely to report hanging out with friends in the last week, 1.22
      (95% CI: 1.01, 1.49) times more likely to report disliking school, and 1.40 (95%
      CI: 1.06, 1.86) times more likely to consider themselves poor students.
      DISCUSSION: Associations of weight status with social relationships, school
      experiences, psychological well-being, and some future aspirations were observed.
      Among girls, the pattern of observations indicates that obese girls reported more
      adverse social, educational, and psychological correlates. Obese as well as
      underweight boys also reported some adverse social and educational correlates.
      These findings contribute to an understanding of how adolescent experiences vary
      by weight status and suggest social and psychological risks associated with not
      meeting weight and body shape ideals embedded in the larger culture.

PMID- 11346667
TI  - Obesity and elevated plasma leptin concentration in oMT1A-o growth hormone
      transgenic mice.
AB  - OBJECTIVE: This study was undertaken to evaluate plasma leptin concentration in
      the regulatable ovine metallothionein-ovine growth hormone (oMT1a-oGH) transgenic
      (TG) mouse model of obesity. RESEARCH METHODS AND PROCEDURES: Transgene stimulus
      (zinc) was provided at 21 days of age to male and female wild-type (WT) and TG
      mice. Plasma leptin concentrations were measured by radioimmunoassay at 42, 63,
      84, and 105 days of age and from inactivated TG mice at 84 and 105 days. RESULTS:
      WT and TG mice did not differ significantly in plasma leptin concentration at any
      of the ages examined (42, 63, 84, and 105 days), although females showed
      consistently higher plasma leptin concentrations than males regardless of
      genotype throughout the duration of the study. Male and female TG mice in which
      the transgene was inactivated at 63 days had a 1.5-fold to 3.5-fold increase in
      plasma leptin concentration over WT mice and continuously activated TG mice at 84
      and 105 days of age. The elevated plasma leptin concentration seen in the
      inactivated TG mice at 84 and 105 days of age reflects the >300% increase in
      white adipose tissue seen in this model and correlated with all adipose depot
      weights and overall body lipid at these later ages. When plasma leptin was
      expressed per gram of total body fat, the leptin adjusted for body lipid was
      significantly higher in WT mice than either continuously activated TG or
      activated and then inactivated TG groups. DISCUSSION: The inactivated TG mice in
      this study had higher plasma leptin levels with increasing total body adiposity,
      but the relative proportion of circulating leptin, on a total body lipid basis,
      was reduced when compared with the WT mice. This reduction was also observed in
      activated TG mice at the older ages. Although the absolute levels of circulating
      leptin were elevated in the inactivated TG animals, the amount of leptin produced
      per gram of fat was lowered. With the inactivation of the transgene, the leptin
      remained depressed after the removal of the elevated growth hormone. This
      represents a potential explanation for the ensuing hypertrophy of the fat depots
      and the abnormal phenotypic response of inactivated TG mice to elevated plasma
      leptin concentrations resulting in the development of obesity.

PMID- 11346668
TI  - Stages of change and weight loss among rural African American women.
AB  - OBJECTIVE: Obesity is a prevalent public health problem in the United States,
      especially for rural African American women, and causes increased morbidity and
      mortality. The purpose of this analysis was to determine whether the
      transtheoretical stages of change model was generalizable to weight loss
      intention among overweight and obese rural African American women and to identify
      important predictors of the stages of change. RESEARCH METHODS AND PROCEDURES:
      The study was conducted in two rural counties in central Virginia. A population
      based sample of 200 women under the age of 40 completed questionnaires concerning
      weight loss behavior and beliefs about weight. Ordinal logistic regression was
      used to predict stage of change. RESULTS: A total of 142 of the 200 women (71%)
      were overweight or obese (body mass index of > or =25) and were classified into a
      stage of change. Overall, 30% of respondents were in the precontemplation stage,
      15% in the contemplation stage, 48% in the preparation stage, 4% in the action
      stage, and 3% in the maintenance stage. Education, what friends think about
      weight, body mass index, and a scale of the positive aspects of weight loss were
      significant predictors of the stage of change (p < 0.05). CONCLUSIONS: Several
      predictors of stage were the same as those found in studies of other health
      behaviors, and this research provides support for applying a stages of change
      model for weight loss intention among rural African American women. Two
      predictors in particular, significance of what friends think about weight and a
      scale of the positive aspects of weight loss, have implications for health
      education initiatives and social support in weight loss interventions.

PMID- 11346669
TI  - Growth of visceral fat, subcutaneous abdominal fat, and total body fat in
      children.
AB  - OBJECTIVE: To examine the patterns of growth of visceral fat, subcutaneous
      abdominal fat, and total body fat over a 3- to 5-year period in white and African
      American children. RESEARCH METHODS AND PROCEDURES: Children (mean age: 8.1 +/-
      1.6 years at baseline) were recruited from Birmingham, Alabama, and those with
      three or more repeated annual measurements were included in the analysis (N = 138
      children and 601 observations). Abdominal adipose tissue (visceral and
      subcutaneous) was measured using computed tomography. Total body fat and lean
      tissue mass were measured by DXA. Random growth curve modeling was performed to
      estimate growth rates of the different body fat compartments. RESULTS: Visceral
      fat and total body fat both exhibited significant growth effects before and after
      adjusting for subcutaneous abdominal fat and lean tissue mass, respectively, and
      for gender, race, and baseline age (5.2 +/- 2.2 cm(2)/yr and 1.9 +/- 0.8 kg/yr,
      respectively). After adjusting for total body fat, the growth of subcutaneous
      abdominal fat was not significant. Whites showed a higher visceral fat growth
      than did African Americans (difference: 1.9 +/- 0.8 cm(2)/yr), but there was no
      ethnic difference for growth of subcutaneous abdominal fat or total body fat.
      There were no gender differences found for any of the growth rates. DISCUSSION:
      Growth of visceral fat remained significant after adjusting for growth of
      subcutaneous abdominal fat, implying that the acquisition of the two abdominal
      fat compartments may involve different physiologic mechanisms. In contrast,
      growth of subcutaneous abdominal fat was explained by growth in total body fat,
      suggesting that subcutaneous fat may not be preferentially deposited in the
      abdominal area during this phase of growth. Finally, significantly higher growth
      of visceral fat in white compared with African American children is consistent
      with cross-sectional findings.

PMID- 11346670
TI  - Scaling VO(2) peak in obese and non-obese girls.
AB  - OBJECTIVE: The conventional ratio method (milliliters O(2) per mass) typically is
      used to express VO(2) peak. The goal of the current study was to compare VO(2)
      peak of obese girls with normal-weight girls by ratio and allometric scaling
      methods. RESEARCH METHODS AND PROCEDURES: We compared VO(2) peak by ratio and
      allometric methods in 46 obese and 47 normal-weight girls. Indirect calorimetry
      was used to measure VO(2) peak during either treadmill running or walking.
      Regression analysis was used to determine coefficients for mass and stature for
      each group with ANOVA used to compare data between groups. RESULTS: The obese
      girls were taller and had higher values of body fatness (p < or = 0.05). Absolute
      VO(2) peak (liters per minute) was similar between groups; however VO(2) peak
      relative to mass was 50% lower (p < or = 0.05) in the obese girls. When VO(2)
      peak (milliliters per minute per kilogram) and mass were correlated, r = -0.48
      was found in the obese group. Allometric scaling of logarithmic transformed
      stature and mass reduced this to r = -0.002, thus eliminating the bias associated
      with the ratio method. Adjusting VO(2) peak allometrically scaled for mass,
      stature, and the combination of mass and stature reduced the difference between
      groups from 50% (ratio method) to 10% to 11% (p < or = 0.05) with higher values
      found in the normal-weight girls. DISCUSSION: These results demonstrate the bias
      associated with the ratio method when comparing VO(2) peak in obese girls with
      VO(2) peak in normal-weight girls. Allometric scaling eliminated the bias and
      thus may reflect a truer comparative response.

PMID- 11346671
TI  - Racial differences in the sums of skinfolds and percentage of body fat estimated
      from impedance in black and white girls, 9 to 19 years of age: the National
      Heart, Lung, and Blood Institute Growth and Health Study.
AB  - OBJECTIVES: This National Heart, Lung, and Blood Institute Growth and Health
      Study report assesses racial differences in fat patterning in black and white
      girls ages 9 to 19 years, comparing the sum of triceps and subscapular skinfolds
      (SSFs) and percentage of body fat (%BF) from impedance as two indices of
      adiposity. It is hypothesized that racial differences in fat patterning manifest
      during puberty. RESEARCH METHODS AND PROCEDURES: SSF and %BF were measured
      annually. Racial differences in SSF and %BF were evaluated by age. Associations
      between %BF and SSF were evaluated using the Pearson's correlations coefficient.
      Classification agreement was evaluated using the kappa-statistic. Effects of
      pubertal stage and race on classification agreement were examined using
      multivariate models. RESULTS: White girls had a greater mean %BF at 9 to 12 years
      of age; black girls had a greater %BF thereafter. Black girls had a greater mean
      SSF at every age. The correlation coefficient between SSF and %BF was 0.79, and
      there was good agreement between %BF and SSF in separating high (>85th
      percentile) from not high (kappa = 0.60 for whites and 0.66 for blacks). SSF
      associated more with %BF in prepuberty and early puberty than in late puberty.
      DISCUSSION: Despite good correlations between %BF and SSF, the two methods
      indicate different fat patterns in black and white girls.

PMID- 11346672
TI  - Is parental control over children's eating associated with childhood obesity?
      Results from a population-based sample of third graders.
AB  - OBJECTIVE: Identifying parental behaviors that influence childhood obesity is
      critical for the development of effective prevention and treatment programs.
      Findings from a prior laboratory study suggest that parents who impose control
      over their children's eating may interfere with their children's ability to
      regulate intake, potentially resulting in overweight. These findings have been
      widely endorsed; however, the direct relationship between parental control of
      children's intake and their children's degree of overweight has not been shown in
      a generalized sample. RESEARCH METHODS AND PROCEDURES: This study surveyed 792
      third-grade children with diverse ethnic and socioeconomic backgrounds from 13
      public elementary schools. Parental control over children's intake was assessed
      through telephone interviews using a state-of-the-art instrument, and children
      were measured for height, weight, and triceps skinfold thickness. RESULTS:
      Counter to the hypothesis, parental control over children's intake was inversely
      associated with overweight in girls, as measured by body mass index, r = -0.12, p
      < 0.05, and triceps skinfolds, r = -0.11, p < 0.05. This weak relationship became
      only marginally significant when controlling for parents' perceptions of their
      own weight, level of household education, and children's age. No relationship
      between parental control of children's intake and their children's degree of
      overweight was found in boys. DISCUSSION: Previous observations of the influence
      of parental control over children's intake in middle-class white families did not
      generalize to 8- to 9-year-olds in families with diverse socioeconomic and ethnic
      backgrounds. The present findings reveal a more complex relationship between
      parental behaviors and children's weight status.

PMID- 11346673
TI  - High-fat diet feeding elevates skeletal muscle uncoupling protein 3 levels but
      not its activity in rats.
AB  - OBJECTIVE: The objective of this study is to test the impact of high-fat diet
      (HFD) feeding on skeletal muscle (SM) uncoupling protein 3 (UCP3) expression and
      its association with mitochondrial ion permeability and whole-body energy
      homeostasis. RESEARCH METHODS AND PROCEDURES: Sprague-Dawley rats were fed ad
      libitum either a HFD (60% of energy from fat, n = 6) or a low-fat diet (12% of
      energy from fat, n = 6) for 4 weeks. Twenty-four-hour energy expenditure was
      measured by indirect calorimetry in the last week of the dietary treatment. Blood
      samples were collected for plasma leptin and free fatty acid assays, and
      mitochondria were isolated from hindlimb SM for subsequent determinations of UCP3
      levels and mitochondrial ion permeability. RESULTS: Plasma leptin levels were
      higher in rats fed the HFD despite the same body weight in two groups. The same
      dietary treatment also rendered a 2-fold increase in plasma free fatty acid and
      SM UCP3 protein levels (Western blot) compared with the group fed the low-fat
      diet. However, the elevated UCP3 protein levels did not correlate with
      mitochondrial swelling rates, a measure of mitochondrial chloride, and proton
      permeability, or with 24-hour energy expenditure. DISCUSSION: The high
      correlation between the levels of plasma free fatty acid levels and SM UCP3
      suggests that circulating free fatty acid may play an important role in UCP3
      expression during the HFD feeding. However, the dissociation between the UCP3
      protein levels and 24-hour energy expenditure as well as mitochondrial ion
      permeability suggests that mitochondrial proton leak mediated by muscle UCP3 may
      not be a major contributor in energy balance in HFD feeding, and other regulatory
      mechanisms independent of gene regulation may be responsible for the control of
      UCP3-mediated uncoupling activity.

PMID- 11346674
TI  - Childhood psychological, physical, and sexual maltreatment in outpatients with
      binge eating disorder: frequency and associations with gender, obesity, and
      eating-related psychopathology.
AB  - OBJECTIVE: To examine rates of reported childhood maltreatment in binge eating
      disorder (BED), and to explore associations with obesity, gender, eating disorder
      features, and associated functioning. RESEARCH METHODS AND PROCEDURES: Subjects
      were 145 consecutive outpatients with BED as defined in the Diagnostic and
      Statistical Manual of Mental Disorders, 4(th) edition. Subjects were interviewed
      and they completed questionnaires to assess eating disorder features and
      functioning. The Childhood Trauma Questionnaire was given to assess childhood
      maltreatment in five domains (emotional abuse, physical abuse, sexual abuse,
      emotional neglect, and physical neglect). RESULTS: A total of 83% of BED patients
      reported some form of childhood maltreatment. A total of 59% of BED patients
      reported emotional abuse, 36% reported physical abuse, 30% reported sexual abuse,
      69% reported emotional neglect, and 49% reported physical neglect. There were no
      differences in the distribution of any form of childhood maltreatment by gender
      or by obesity status. The different forms of maltreatment were not associated
      with variability in current body mass index, binge eating, or in the attitudinal
      features of eating disorders. Only one of the five forms of maltreatment
      (physical neglect) was associated with dietary restraint in women. Emotional
      abuse was significantly associated with greater body dissatisfaction, higher
      depression, and lower self-esteem in men and women and sexual abuse was
      associated with greater body dissatisfaction in men. The different forms of
      maltreatment were unrelated to the age at onset of overweight, dieting, or binge
      eating. DISCUSSION: BED outpatients reported a wide range of childhood
      experiences of maltreatment that do not differ by gender or obesity status.
      Different forms of maltreatment were not associated with the onset of overweight,
      dieting, or binge eating, or with variability in current body mass index or
      eating disorder features (except for one association between physical neglect and
      dietary restraint). Reports of emotional abuse were associated with greater body
      dissatisfaction and depression and lower self-esteem in men and women and sexual
      abuse with greater body dissatisfaction in men.

PMID- 11346675
TI  - Effect of scalp and facial hair on air displacement plethysmography estimates of
      percentage of body fat.
AB  - OBJECTIVE: The objective of this study was to determine the effect of body hair
      (scalp and facial) on air displacement plethysmography (BOD POD) estimates of
      percentage of body fat. RESEARCH METHODS AND PROCEDURES: A total of 25 men (31.4
      +/- 8.0 years, 83.4 +/- 12.2 kg, 181.8 +/- 6.9 cm) agreed to grow a beard for 3
      weeks to participate in the study. Total body density (g/cm(3)) and percentage of
      body fat were evaluated by BOD POD. To observe the effect of trapped isothermal
      air in body hair, BOD POD measures were performed in four conditions: criterion
      method (the beard was shaven and a swimcap was worn), facial hair and swimcap,
      facial hair and no swimcap, and no facial hair and no swimcap(.) RESULTS: The
      presence of only a beard (facial hair and swimcap) resulted in a significant
      underestimation of percentage of body fat (16.2%, 1.0618 g/cm(3)) vs. the
      criterion method (17.1%, 1.0597 g/cm(3), p < 0.001). The effect of scalp hair (no
      swim cap worn) resulted in a significant underestimation in percentage of body
      fat relative to the criterion method, either with facial hair (facial hair and no
      swimcap; 14.8%, 1.0649 g/cm(3)) or without facial hair (no facial hair and no
      swimcap; 14.8%, 1.0650 g/cm(3), p < 0.001 for both). DISCUSSION: A significant
      underestimation of percentage of body fat was observed with the presence of
      facial hair ( approximately 1%) and scalp hair ( approximately 2.3%). This
      underestimation in percentage of body fat may be caused by the effect of trapped
      isothermal air in body hair on body-volume estimates. Thus, excess facial hair
      should be kept to a minimum and a swimcap should be worn at all times to ensure
      accurate estimates of body fat when using the BOD POD.

PMID- 11346676
TI  - Resting energy expenditure: systematic organization and critique of prediction
      methods.
AB  - There are many published methods for predicting resting energy expenditure (REE)
      from measured body composition. Although these published reports extend back
      almost a century, new related studies appear on a regular basis. It remains
      unclear what the similarities and differences are among these various methods and
      what, if any, advantages the newly introduced REE prediction models offer. These
      issues led us to develop an organizational system for REE prediction methods with
      the goal of clarifying prevailing ambiguities in the field. Our classification
      scheme is founded on body composition level (whole-body, tissue-organ, cellular,
      and molecular) and related components as the REE predictor variables. Each
      existing REE prediction method by body composition must belong to one body
      composition level. The suggested classification system, founded on a conceptual
      basis, highlights similarities and differences among the diverse REE-body
      composition prediction methods, provides a framework for teaching REE-body
      composition relationships, and identifies important future research
      opportunities.

PMID- 11346677
TI  - Docetaxel: overview of an active drug for breast cancer.
AB  - Docetaxel and paclitaxel differ in their precise molecular targets and
      pharmacokinetics. Docetaxel is more avidly taken up by tumor cell lines than
      paclitaxel, and its efflux is slower. Comparative cytotoxicity data suggest
      greater potency. These factors may help explain the clinical differences that
      have been observed between the taxanes in patients with breast cancer.

PMID- 11346678
TI  - Taxane/anthracycline combinations: setting a new standard in breast cancer?
AB  - Among the novel chemotherapeutic drugs introduced in the 1990s, the taxanes have
      emerged as the most powerful compounds in breast cancer. Both compounds,
      paclitaxel and docetaxel, have been evaluated in metastatic settings before
      adjuvant trials proceeded. Docetaxel was shown in several phase III trials to be
      superior, particularly in terms of survival, for salvaging polychemotherapies
      after failure of prior chemotherapy, including that with anthracyclines. A
      benefit of docetaxel was also reported when compared with doxorubicin after
      failure of alkylating agents. In phase III trials paclitaxel was reported to be
      as efficacious over 24 hours as doxorubicin 60 mg/m(2), while paclitaxel was
      significantly inferior to doxorubicin 75 mg/m(2) over 3 hours and was close to
      CMF in another trial. The role of taxanes in combination with anthracyclines in
      first-line therapy of advanced breast cancer is emerging. Following several phase
      II studies, a phase III trial showed the significant superiority of
      docetaxel/doxorubicin (AT) versus doxorubicin/cyclophosphamide (AC) in terms of
      response and time to progression. In several phase II studies with paclitaxel (3
      hours), anthracyclines in the metastatic setting showed high efficacy but
      produced cardiac toxicity related to a pharmacokinetic interaction between the
      two agents. This finding led to the implementation of metastatic strategies
      (phase III trials) aimed at avoiding the pharmacokinetic interaction, while the
      adjuvant strategies with paclitaxel focused primarily on the sequential approach
      (AC followed by paclitaxel). In contrast, adjuvant strategies with
      docetaxel/anthracycline-based programs were implemented following both sequential
      and combination approaches.

PMID- 11346679
TI  - Docetaxel and epirubicin in advanced breast cancer.
AB  - In an International Breast Cancer Study Group phase I/II program, 70 patients
      with advanced breast cancer received up to eight courses of 75 mg/m2 docetaxel
      combined with 90 mg/m(2) epirubicin, every 3 weeks. G-CSF was not administered
      prophylactically. Grade 4 neutropenia occurred in 88% of cycles that were not
      supported by G-CSF. However, febrile neutropenia affected only 24% of cycles. It
      occurred after the first cycle in 56% of cases and was managed by oral
      antibiotics in 52% of cases. When supportive G-CSF was administered, the
      incidence of febrile neutropenia fell to 3% and grade 4 neutropenia to 41%. Only
      6% of patients experienced a greater than 20% reduction in left ventricular
      ejection fraction and no severe, irreversible cardiotoxicity was observed. The
      overall response rate (RR) was 66% and median time to progression was 4.5 months.
      The RR was similar in patients with prior adjuvant chemotherapy and patients with
      predominantly visceral disease. These data and those of comparable series suggest
      that the combination of epirubicin and docetaxel is tolerable and active, and
      that it should be further developed clinically.

PMID- 11346680
TI  - Nonanthracycline containing docetaxel-based combinations in metastatic breast
      cancer.
AB  - Many active nonanthracycline-containing regimens are emerging from clinical
      trials and may offer the option of treating metastatic breast cancer without
      resorting to doxorubicin or analogues. When used first-line in metastatic breast
      cancer, both cisplatin and carboplatin are active agents and hence candidates for
      combination therapy. In a dose-finding study in patients with no prior
      chemotherapy for metastatic disease, docetaxel administered together with
      cisplatin produced a promising response rate (RR) of 60% (73% in patients without
      prior adjuvant chemotherapy). The combination is feasible, although adequate
      hydration and antiemetic medication must be given. There is also an early
      indication that it may be possible to dramatically cytoreduce disease in patients
      with locally advanced breast cancer who are treated with docetaxel plus
      cisplatin. Given its lower toxicity, carboplatin may also have a role in
      combination with the taxanes. Of the nonplatinum agents, vinorelbine appears to
      hold promise; its combination with docetaxel produced an RR of 59% in a group of
      anthracycline-pretreated patients with progressive disease. Forty-two percent of
      the patients studied also had prior exposure to a taxane. Weekly gemcitabine plus
      monthly docetaxel is feasible and active, as is the combination of docetaxel q 3
      weeks with daily oral capecitabine.

PMID- 11346681
TI  - Docetaxel and herceptin: foundation for future strategies.
AB  - Randomized controlled studies have demonstrated that both docetaxel and Herceptin
      are capable of increasing survival in patients with metastatic breast cancer. The
      two agents show synergy in vitro, and their use in combination is not likely to
      be associated with the problem of enhanced cardiotoxicity. In two trials of
      Herceptin plus docetaxel in patients with advanced breast cancer, preliminary
      data are available for 35 patients. These early results show that the combination
      is well-tolerated. No symptomatic cardiotoxicity has occurred. The preliminary
      response rates (RR) in these first- and second-line patients are 44% in one study
      and 63% in the other. In the subgroups of patients who were HER-2 3+
      overexpressers, the RRs are currently 55% and 73%. In an attempt to maximize the
      efficacy of Herceptin, its use has also been studied in combination with
      docetaxel and a platinum salt, producing a preliminary RR of 78% in patients
      positive for HER-2 on the fluorescence in situ hybridization assay. These data
      are sufficiently promising to justify a study of the role of Herceptin in
      combination with adjuvant chemotherapy regimens containing docetaxel or docetaxel
      plus a platinum. The combination of Herceptin with adjuvant therapy containing
      docetaxel and a platinum may provide a helpful alternative to the potentially
      cardiotoxic Herceptin/anthracycline-containing regimens currently under
      investigation.

PMID- 11346682
TI  - Weekly docetaxel in breast cancer: applying clinical data to patient therapy.
AB  - The use of weekly 35-40 mg/m2 docetaxel, typically on a schedule of 6 weeks of
      therapy followed by a 2-week break, has produced response rates ranging from 33%
      50% in patients with advanced breast cancer, the majority of whom have already
      received chemotherapy. These encouraging levels of response are seen across
      disease sites and in patients with prior anthracycline exposure. Importantly, the
      weekly administration of docetaxel allows prolonged treatment to a high
      cumulative dose: the weekly regimen is minimally myelotoxic, and neuropathy and
      other adverse events are infrequent. Weekly single-agent docetaxel may be a
      useful therapy in particular groups of patients such as those with reduced bone
      marrow reserve. It may also be a helpful means of delivering a highly active
      cytotoxic drug in combination with radiation therapy, other proven chemotherapy
      agents such as doxorubicin, and new, highly promising biological agents such as
      HERCEPTIN:

PMID- 11346683
TI  - Theoretical concepts and the emerging role of taxanes in adjuvant therapy.
AB  - The proven benefits of adjuvant chemotherapy on disease-free and overall survival
      in breast cancer can be explained by concepts of cell kill. Interventions which
      result in greater log kill can be expected to produce improved clinical results.
      The application of log-kill concepts to human breast cancer growth, which appears
      to follow Gompertzian kinetics, suggests not only that the use of non-cross
      resistant drugs is important, but that dose-dense schedules may have an advantage
      over conventional schedules of drug administration. Sequential therapy may allow
      dose-dense administration of cytotoxic agents and encourage the integration of
      new biological agents into combination regimens, particularly with the taxanes.
      Ongoing trials in these concepts are reviewed.

PMID- 11346684
TI  - Neoadjuvant therapy in breast cancer: can we define its role?
AB  - It remains unclear whether neoadjuvant therapy increases disease-free survival
      when compared with an approach in which chemotherapy is delayed until after
      surgery. However, the current rationale for neoadjuvant therapy is based on its
      usefulness in quickly evaluating the likely benefit of new approaches to
      treatment and tailoring therapy to the biological characteristics of the
      individual tumor. In the primary therapy of breast cancer, the Aberdeen study
      shows that patients unresponsive to an anthracycline-based neoadjuvant regimen
      may achieve a response when switched to docetaxel. Further, patients with an
      initial clinical response to CVAP were more likely to show a pathological
      complete response (pCR) at final assessment when four cycles of CVAP were
      followed by four of docetaxel than when CVAP was maintained for eight cycles (pCR
      rate 34% versus 16%). Early data suggest that this difference translates into
      significantly lengthened progression-free survival. As in other disease settings,
      it may be possible to devise nonanthracycline-containing neoadjuvant regimens
      which are at least as effective as those in current use.

PMID- 11346685
TI  - Novel compounds in the therapy of breast cancer: opportunities for integration
      with docetaxel.
AB  - Increasingly, novel agents are being developed specifically at inhibition of
      growth factor receptors and events within the signal transduction pathway. These
      agents include the epidermal growth factor tyrosine kinase inhibitors, the
      farnesyl transferase inhibitors, and bcl-2 antisense oligonucleotides. Along with
      these new approaches to molecular targeting, it will be necessary to develop new
      study designs for drug evaluation. Target validation in both normal surrogate
      tissues and tumor tissue becomes increasingly relevant in early clinical trials.
      Furthermore, antitumor efficacy may no longer correlate with normal hematological
      or nonhematological toxicity, and it may be more appropriate in phase I trials to
      identify the maximum target inhibition dose rather than the maximum tolerated
      dose. Moreover, measures of cytoreduction, such as complete and partial response,
      may be less relevant than disease stabilization for some of these novel agents
      which have limited cytotoxic effects and would be considered cytostatic agents.
      Assessment of single-agent activity and the future role in conjunction with
      cytostatic agents represents the single most important challenge facing the
      clinical development of these molecular targeted therapies.

PMID- 11346686
TI  - Lessons learned.

PMID- 11346687
TI  - Is undertransfusion occurring?

PMID- 11346688
TI  - Cryopreservation of HPCs for clinical use.

PMID- 11346689
TI  - Assessment of blood administration procedures: problems identified by direct
      observation and administrative incident reporting.
AB  - BACKGROUND: Adverse events in blood administration frequently involve the
      identification of transfusion recipients or components. This report details the
      results of an investigation of the efficacy of direct observation and that of a
      hospital-wide incident-reporting system in detecting standard operating
      procedures (SOPs) for deviations in blood administration. STUDY DESIGN AND
      METHODS: A process-driven audit form targeting 19 blood administration steps was
      developed for direct observation monitoring of blood administration. Over 18
      months, 202 transfusions were observed in selected hospital locations. Data from
      this audit were compared with data collected from the incident reporting system.
      RESULTS: Through direct observation, 334 events were identified for a rate of
      1.65 SOP deviations per transfusion. The incident reporting system identified 52
      adverse events. Deviations were categorized as being related to the patient or
      component information, transfusion, patient monitoring, record documentation, and
      ordering or delivery of the component. Fifty-five percent of the events detected
      with direct observation related to identification of the patient or component,
      compared with 17 percent of incident reports. Using direct observation, 9 percent
      of transfused patients had wristband identification deviations. Such SOP
      deviations were not detected with the incident reporting system. Transfusion SOP
      deviations represented 15 percent of direct observation reports and 38 percent of
      incident reports. Direct observation identified deviations in monitoring
      practices and record documentation not detected by incident reporting.
      CONCLUSION: Direct observation appears to be an effective means for identifying
      deviations related to patient identification, patient monitoring, and record
      documentation.

PMID- 11346690
TI  - Monitoring for underutilization of RBC components and platelets.
AB  - BACKGROUND: Monitoring blood transfusion for overutilization is standard practice
      at most institutions. STUDY DESIGN AND METHODS: This study monitored for
      underutilization of blood transfusion over a 14-month period, by evaluating
      patients who had Hb levels that were reported to be <5 g per dL or platelet
      counts <10 x 10(9) per L and who did not receive an RBC or platelet transfusion
      within 24 hours of the reported results. RESULTS: During the study period, 24,004
      units of RBCs and 3,967 units of apheresis platelets were transfused. There were
      148 patients who had a Hb level that was reported to be <5 g per dL or a platelet
      count reported to be <10 x 10(9) per L and who did not receive a transfusion
      during the 24 hours after the reporting of these results. In 5 cases, the
      patients died before the reporting of the low Hb or platelet counts, which
      precluded the low Hb or low platelet count reports from triggering transfusion
      therapy. In 8 cases, an underutilization review investigation could not be done,
      because of the unavailability of patient charts. Of the remaining 135 cases,
      investigation revealed justifiable reasons for withholding transfusion in 133. In
      2 cases, the withholding of transfusion was deemed by peer review to be
      inappropriate, as the patients should have received a transfusion. Overall, there
      was one documented underutilization of RBC transfusion therapy during a period
      when 24,004 units were transfused and one underutilization of platelet
      transfusion therapy during a period when 3,967 units of apheresis platelets were
      transfused. CONCLUSION: Monitoring for underutilization of transfusion therapy
      fulfills the requirements of the Joint Commission on the Accreditation of
      Healthcare Organizations: While the underutilization of transfusion therapy did
      not appear to be a significant problem at this medical center, determining the
      reasons for withholding transfusions shed light on important patient care-related
      issues, including preexisting causes of falsely low platelet counts and Hb
      levels, delays in investigating critical laboratory values, and the need for
      policies for the treatment of patients who refuse transfusion for personal or
      religious reasons.

PMID- 11346691
TI  - Evaluation of oxygen extraction ratio as a physiologic transfusion trigger in
      coronary artery bypass graft surgery patients.
AB  - BACKGROUND: Approximately 20 percent of all allogeneic blood transfusions are
      administered in connection with coronary artery bypass graft (CABG) operations.
      Transfusion practices vary across the country. The whole-body oxygen extraction
      ratio (O2 ER) reflects the adequacy of the patient's response to acute
      normovolemic anemia with an O2 ER of approximately 50 percent being shown to be
      an appropriate transfusion trigger. The present study monitored the O2 ER in
      patients undergoing CABG and determined if transfusion practices would have been
      different if an O2 ER > or = 45 percent were used as a transfusion trigger. STUDY
      DESIGN AND METHODS: Seventy patients with a postoperative Hct < = 25 percent were
      the test subjects. Arterial and mixed venous contents were determined before the
      operation, in the intensive care unit after the operation, and 12 hours after the
      operation. RESULTS: There were no deaths. Forty-one patients received allogeneic
      transfusion. These patients were older, weighed less, and had a preoperative Hct
      lower than the nontransfused patients. There were no significant differences
      between transfused and nontransfused patients with respect to postoperative Hct
      (21.0 +/- 0.4 vs. 22.2 +/- 0.4), cardiac index (2.5 +/- 0.1 vs. 2.7 +/- 0.1), O2
      delivery (6.4 +/- 0.3 vs. 6.7 +/- 0.3), O2 consumption (2.5 +/- 0.1 vs. 2.5 +/-
      0.1), and O2 ER (38.3 +/- 1.7 vs. 37.5 +/- 1.5). In the transfusion group, 7 of
      21 patients had a postoperative O2 ER > or = 45 percent, while 3 of 35 in the
      nontransfused group had that result. CONCLUSION: The use of O2 ER as a
      transfusion trigger as part of a transfusion algorithm could lead to a reduction
      in allogeneic blood transfusion.

PMID- 11346692
TI  - RBC transfusion in sickle cell anemia (HbSS): experience from the Jamaican Cohort
      Study.
AB  - BACKGROUND: RBC transfusion is widely advocated in the management of sickle cell
      anemia (SCA), but it carries potentially serious risks, especially in the setting
      of chronic transfusion. The Jamaican Sickle Cell Clinic is conservative in its
      use of transfusion, and this experience is presented to allow comparison with
      other centers in defining the role for transfusion in SCA. STUDY DESIGN AND
      METHODS: Reported here is a retrospective, descriptive study of all RBC
      transfusions given to 311 subjects with SCA who were followed in a cohort study
      from birth and are, at this writing, 16.3 to 24.7 years old. RESULTS: There were
      520 transfusion episodes in 197 (63.3%) of the 311 subjects; 1 transfusion in 80
      (41%) of those who received transfusion(s), 2 transfusions in 54 (27%), 3
      transfusions in 21 (11%), 4 in 17 (9%), 5 in 9 (5%), and 6 or more in 16 (8%).
      Single transfusions were usual for acute anemia of aplastic crises or acute
      splenic sequestration, and multiple transfusions (up to 21 episodes) were usual
      in the prophylaxis of recurrent stroke. Indications were aplastic crisis (102),
      acute chest syndrome (90), acute splenic sequestration (75), stroke (62),
      septicemia (46), hypoplasia (40), hypersplenism (34), surgery (31),
      gastroenteritis (10), and miscellaneous (30). CONCLUSION: Despite conservative
      transfusion use, 70.6 percent of patients had received at least one transfusion
      by 20 years of age in the Jamaican Sickle Cell Clinic:

PMID- 11346693
TI  - Prolonged iron depletion after allogeneic 2-unit RBC apheresis.
AB  - BACKGROUND: Allogeneic 2-unit RBC apheresis is a safe procedure offering many
      advantages for donors and blood banks. A controlled study was performed to
      determine whether the recommended minimum interval of 4 months between 2-unit RBC
      apheresis donations is appropriate in terms of the recovery of RBCs and the
      regeneration of iron stores. STUDY DESIGN AND METHODS: Twenty male subjects each
      donated 2 units of RBCs by apheresis. The RBC count, reticulocyte count, EPO, and
      measures of iron status were analyzed before and during the 4 months after
      donation. RESULTS: A significant decrease in Hb (15.89 +/- 0.82 [mean +/- SD] vs.
      14.08 +/- 0.97 mg/dL, baseline vs. Day 7; p<0.001) was equalized within 2 months.
      In contrast, ferritin values declined significantly from 54.2 +/- 33.7 to 23.42
      +/- 21.94 microg per L (predonation vs. Day 30) and remained significantly below
      predonation values, but within the normal range, until the end of the study
      period. CONCLUSION: A donation interval of 4 months is appropriate in terms of
      RBC recovery, but may not be appropriate in terms of iron store regeneration. The
      tendency to shorten the donation interval should be reconsidered in light of the
      measurements of iron storage. The use of ferritin levels is recommended as a
      preselection criterion for allogeneic 2-unit RBC apheresis.

PMID- 11346694
TI  - Outcomes of a program to evaluate mother and baby 6 months after umbilical cord
      blood donation.
AB  - BACKGROUND: A routine program of evaluating mothers and infants 6 months after
      umbilical cord blood donation was started at the Milano Cord Blood Bank (MCBB) in
      1996. This study evaluated the main outcomes of this program. STUDY DESIGN AND
      METHODS: All mothers donating cord blood at this bank from February 1996 through
      May 1999 were invited to visit the bank or the collection suite 6 months after
      delivery to report on the health condition of their babies and to provide a fresh
      blood sample for repeat basal serologic tests (HBsAg, anti-HCV, anti-HIV-1/2, and
      syphilis). A bank volunteer contacted the mothers by telephone to schedule their
      visits just before the expiration of the 6-month period. Before collection of the
      new sample, a trained operator interviewed the mothers to review the mother's
      medical history information collected at donation and to obtain the baby's
      postnatal medical history. RESULTS: Of the 2450 mothers enrolled in the study,
      2315 (94.5%) attended the bank in agreement with the program, 4 promised to
      attend, 95 could not be traced, 26 declined the invitation, and 10 were unable to
      attend. Of the 135 mothers who could not be traced, 29 (21.4%) belonged to non
      European ethnic groups. The average time spent with each mother was approximately
      20 minutes. In serologic testing, one indeterminate anti-HCV seroconversion (c22)
      was detected. Collection of the baby's postnatal history reported one case of
      congenital urinary malformation not known at delivery, one of protein C
      deficiency, one of phenylketonuria, one of mucoviscidosis, and one of 10q-
      chromosomal abnormality. The cord blood components from all these births were
      discarded. CONCLUSION: These data support the feasibility of a routine 6-month
      program of evaluating mothers and babies giving cord blood at a cord blood bank.
      Such programs may increase the quality of components stored for transplantation.

PMID- 11346695
TI  - Transfusion of incompatible RBCs to a patient with alloanti-Kp(b).
AB  - BACKGROUND: The finding of an antibody that reacts against a high-incidence blood
      group antigen always constitutes a complex transfusion problem because of the
      difficulty in finding compatible units. When the transfusion of incompatible RBCs
      is imperative, it would be of great interest to have access to techniques
      facilitating the prediction of the transfusion outcome. STUDY DESIGN AND METHODS:
      The case of a patient with alloanti-Kp(b) who required RBC transfusions is
      reported. The functional activity of this antibody was assessed by both the
      chemiluminescence test (CLT) and the survival of 51Cr-labeled RBCS: RESULTS: The
      CLT showed an opsonic index of 0.8 with Kp(b)-positive RBCs (normal values up to
      1.6) in pretransfusion studies. During an elective surgical procedure, the
      patient required the transfusion of one incompatible unit of RBCs, which did not
      produce hemolysis. Two weeks after this incompatible transfusion, the opsonic
      index had risen to 11. Results of the 51Cr in vivo study, also performed at that
      time, indicated 24.3 percent survival of Kp(b)-positive RBCs at 60 minutes and
      2.0 percent at 24 hours. CONCLUSION: Results of the CLT correlated with the in
      vivo transfusion outcome and later with the 51Cr survival study.

PMID- 11346696
TI  - A possible role for maternal HLA antibody in a case of alloimmune neonatal
      neutropenia.
AB  - BACKGROUND: Alloimmune neonatal neutropenia (ANN) is caused by a reaction of
      maternal alloantibodies with paternally inherited antigens on the fetal
      neutrophils. While human neutrophil antigens (HNA) antibodies are found in half
      of ANN cases, specific antibodies have not been defined in the remaining cases.
      STUDY DESIGN AND METHODS: Reported here is a neonate with omphalitis due to
      neutropenia. To elucidate the cause of ANN, flow cytometric and PCR analyses were
      used. Reactions of the patient's and mother's sera with neutrophils, lymphocytes,
      and platelets were examined by lymphocytotoxicity test (LCT), anti-human
      immunoglobulin-LCT, and mixed passive hemagglutination test. RESULTS: The
      maternal sera reacted with neutrophils, lymphocytes, and platelets of the patient
      and father. The platelet adsorption eliminated the reaction of the maternal serum
      with the patient's neutrophils. The HLA typing of the family and an LCT using a
      panel of lymphocytes of 20 HLA-typed donors showed HLA-A2 antigen as a target of
      antibodies in the maternal serum. According to anti-human immunoglobulin-LCT, the
      anti-HLA-A2 was present in the neonatal serum. On the other hand, HNA antibodies
      were not detectable in the patient's or the mother's serum. CONCLUSION: These
      results suggest that the transplacental passage of the maternal HLA antibody
      caused neutropenia in this patient.

PMID- 11346697
TI  - Optimizing pretransfusion antibody detection and identification: a parallel,
      blinded comparison of tube PEG, solid-phase, and automated methods.
AB  - BACKGROUND: The ideal pretransfusion testing strategy identifies maximal
      significant antibodies at minimal cost. Objectives of this study were to compare
      the characteristics of three testing methods and determine their optimal
      incorporation into the following generic testing sequence: 1) screen, for
      antibodies 2) if results are positive, use primary identification method, 3) if
      results are inconclusive, use secondary identification method. STUDY DESIGN AND
      METHODS: A total of 2000 consecutive, unselected, coded specimens were tested
      with three screening methods-PEG IAT, manual and automated solid phase red cell
      adherence assay (SPRCA). Of 202 positive results, 187 were of sufficient volume
      and were tested with both PEG and manual SPRCA identification panels, yielding 82
      with significant antibodies, plus one that was negative by both methods found on
      retrospective review of nonstudy results. Calculations were made on the 1985
      volume-sufficient specimens, simulating the possible testing permutations.
      RESULTS: Manual SPRCA was the most sensitive antibody screen (67/83 = 81%) and
      the least specific (1840/1902 = 97%); automated SPRCA was the least sensitive
      (54/83 = 65%) and most specific (1883/1902 = 99%); and PEG was intermediate in
      both sensitivity (64/83 = 77%) and specificity (1860/1902 = 98%). Of the
      identification panels, manual SPRCA identified more antibodies than PEG (67
      versus 66) but had more inconclusive results (41 versus 20). Of overall
      strategies, manual SPRCA screening with either sequence of identification methods
      identified the most antibodies (66). The combination of PEG screen, PEG
      identification, and manual SPRCA identification identified slightly fewer
      antibodies (63) but had the lowest reagent cost, total (reagent plus labor) cost,
      and cost per antibody identified. The sequence of automated SPRCA screening with
      manual SPRCA identification, and PEG identification had the lowest hands-on time.
      CONCLUSIONS: The most cost-effective pretransfusion strategy is PEG screen with
      PEG identification, plus manual SPRCA identification when PEG identification is
      inconclusive.

PMID- 11346698
TI  - A novel microplate agglutination method for blood grouping and reverse typing
      without the need for centrifugation.
AB  - BACKGROUND: Current agglutination tests and solid-phase adherence methods,
      employed as the techniques for RBC typing and antibody screening, require
      centrifugation and washing steps. This report describes a novel agglutination
      method for forward and reverse grouping that is based on the formation of an RBC
      monolayer on a microplate without the need for centrifugation and washing. STUDY
      DESIGN AND METHODS: In a comparative study, 2225 samples from healthy regular
      blood donors were tested for ABO, Rh (D, C, c, E, and e), K, and reverse
      grouping, in parallel, by the new microplate agglutination method and a
      commercially available blood testing system, which served as a reference method.
      RESULTS: In the case of forward grouping, 0.37 percent of samples tested were
      false negative in the new method and 1.35 percent tested false negative in the
      reference blood testing system. In addition, the reverse grouping reference
      method showed 0.4 percent false-positive and 2.6 percent false-negative results.
      In contrast, the new method gave false-positive results in only 0.09 percent and
      false-negative results in 0.67 percent of the cases tested. CONCLUSION: These
      results, as well as the possibility of adapting this method to a fully automated
      system, suggest that our novel agglutination method could be an important
      contribution to the field of immunohematology.

PMID- 11346699
TI  - Posttransfusion purpura secondary to an alloantibody reactive with HPA-5a
      (Br(b)).
AB  - BACKGROUND: Posttransfusion purpura (PTP) is characterized by severe
      thrombocytopenia following blood transfusion that results from alloimmunization
      to platelet-specific alloantigens. Most cases involve antibodies against HPA-1a
      in homozygous HPA-1b persons. CASE REPORT: A patient developed PTP after
      cardiopulmonary bypass associated with a platelet-specific antibody with strong
      reactivity against HPA-5a (Br(b)). Geno-typing confirmed that the patient was
      homozygous for HPA-5b. CONCLUSION: This is the first well-documented occurrence
      of PTP associated with isolated allosensitization to HPA-5a or Br(b). The case
      highlights the importance of maintaining a high level of suspicion for PTP in the
      appropriate clinical setting, even in an atypical patient.

PMID- 11346700
TI  - Donor WBCs can persist and transiently mediate immunologic function in a murine
      transfusion model: effects of irradiation, storage, and histocompatibility.
AB  - BACKGROUND: Donor WBCs are responsible for numerous transfusion complications,
      but little is known concerning the natural history of their clearance following
      transfusion or of their function in the recipient's circulation. A murine
      transfusion model was developed to investigate the effects of blood component
      characteristics and histocompatibility on donor WBC survival kinetics and
      function. STUDY DESIGN AND METHODS: To investigate the effects of storage and
      irradiation, fresh whole blood and blood stored for 1, 2, and 6 weeks at 4
      degrees C, all from male C57b (H2K(b)) mice, was transfused to female Balb/c
      (H2K(d)) mice. To study the effect of histocompatibility, blood was also
      transfused from C57b mice to Balb/c, FVB, C3H, and SW (outbred) mice. To
      investigate the xenogeneic setting, blood from humans, rats, and rabbits was
      transfused to Balb/c mice. Samples were collected weekly after transfusion, and
      the donor WBCs were analyzed, targeting the Y-chromosome with quantitative PCR.
      To investigate donor WBC function, dinitrochlorobenzene (DNCB) sensitivity was
      induced in donor and recipient mice, and the transfusion recipients were observed
      for hypersensitivity to DNCB. RESULTS: Donor WBCs had reduced in vivo survival
      equivalent to their period of storage ex vivo at 4 degrees C. Irradiation of
      donor blood produced no observable difference in donor WBC survival. Allogeneic
      male donor WBCs persisted (100-<1 cell/microL) in female Balb/c recipient mice
      blood over 6 weeks. Donor WBC survival kinetics displayed an early MHC-dependent
      phase, which was followed by a more rapid phase that was not influenced by donor
      recipient MHC differences. All donor WBCs were cleared within 24 to 48 hours.
      DNCB sensitivity was passed through transfusion, where it was transiently
      expressed in naive recipients. CONCLUSION: The clearance of donor WBCs in the
      murine transfusion model is much slower than that in humans. Allogeneic donor WBC
      clearance may be biphasic, involving MHC-dependent as well as MHC-independent
      mechanisms. DNCB sensitivity can be transferred transiently to a naive recipient.

PMID- 11346701
TI  - Performance characteristics of the COBAS AmpliScreen HIV-1 test, version 1.5, an
      assay designed for screening plasma mini-pools.
AB  - BACKGROUND: The COBAS AmpliScreen HIV-1 test, version 1.5 (v1.5) (Roche Molecular
      Systems), is designed for screening pools composed of samples from 24 individual
      units of blood or plasma. A specimen-processing procedure (Multiprep)
      simultaneously concentrates and extracts HIV-1, HCV, and HBV particles from
      plasma and incorporates an HIV-1 internal control (IC) RNA. Processed samples are
      amplified by RT-PCR using HIV-1-specific primers and detected by hybridization of
      the amplified products to HIV-1- and IC-specific oligonucleotide probes. STUDY
      DESIGN AND METHODS: Plasma samples containing known quantities of HIV-1 were used
      to evaluate analytical sensitivity and precision and to validate a pool testing
      algorithm. Analytical specificity was evaluated by adding various viruses and
      bacteria to HIV-1-negative plasma. Seroconversion panels were tested to estimate
      the window-period reduction achieved by RNA testing. RESULTS: The analytical
      sensitivity of the test (concentration that yields > or = 95% positive results in
      a set of replicate tests) was 25 copies of HIV-1 RNA per mL of pooled plasma.
      Representative strains from all HIV-1 group M subtypes were reproducibly detected
      (> 95% positive results) at concentrations of 20 to 200 viral particles per mL.
      The test did not cross-react with a set of 31 viral and 5 bacterial isolates, and
      it yielded negative results on a panel of 500 blood samples from HIV-1
      seronegative donors. Plasma samples containing abnormally high levels of Hb,
      albumin, triglycerides, or bilirubin did not interfere with the test. HIV-1 RNA
      was detected 2 to 14 days before HIV-1 antibody and 0 to 28 days before p24
      antigen. The test specifically detected pools containing a single positive unit
      with 2400 HIV-1 RNA copies per mL and correctly identified the positive unit.
      CONCLUSION: The COBAS AmpliScreen HIV-1 test, v1.5, has sufficient sensitivity to
      detect a single infected unit containing 600 copies of HIV-1 per mL in a pool
      with 23 uninfected units and should reduce the window period between infection
      and seroconversion by at least 2 to 14 days.

PMID- 11346702
TI  - Value of anti-HBc screening of blood donors for prevention of HBV infection:
      results of a 3-year prospective study in Northwestern Greece.
AB  - BACKGROUND: The risk of infection with transfusion-transmitted viruses has been
      reduced remarkably. However, a zero-risk blood supply remains a popular goal.
      Some authorities have introduced the screening for antibody to HBc (anti-HBc) as
      a surrogate test for the presence of several infectious agents. A 3-year
      prospective study was conducted in the Epirus region of Greece to determine the
      prevalence of several blood-borne viruses. One component of the study was the
      prevalence of HBV infection markers and the potential value of anti-HBc testing
      of donors in this area. STUDY DESIGN AND METHODS: Between January 1, 1995, and
      December 31, 1997, some 6696 donors were investigated for the presence of HBV
      infection markers by standard EIAS: Every sample that tested HBsAg-negative but
      anti-HBc-reactive alone or in combination with either or both antibodies to HBV e
      antigen (anti-HBe) and low-titered antibodies to HBsAg (anti-HBs <20 mIU/mL) was
      further investigated for the presence of HBV DNA by a combination of PCR and DNA
      EIA. RESULTS: Of these 6696 donors, 15.8 percent tested positive for at least one
      serologic marker of HBV infection (HBsAg prevalence, 0.85%). Anti-HBc reactivity
      alone or in combination with either or both anti-HBe and low-titered anti-HBs was
      found in 282 donors (4.2%). None tested HBV-DNA positive. No transfusion
      associated HBV infections were recorded in the recipients of the above 282 blood
      units. CONCLUSION: A moderate prevalence of HBV infection markers was found.
      However, taking into account previous studies from this region, it appears that
      the HBsAg prevalence has declined. In addition, the present study cannot
      recommend the introduction of anti-HBc screening as a surrogate marker of occult
      HBV infection. The adoption of this exclusion criterion in this region would
      result in unacceptably high rejection rates among otherwise healthy donors. The
      absence of any case of transfusion-associated HBV infection after the transfusion
      of all HBsAg-negative, anti-HBc-positive units appears to provide further support
      for the negative HBV DNA results. Before a consideration of screening donors,
      efforts must be focused on reducing the number of false-positive anti-HBc
      results.

PMID- 11346703
TI  - IL-10 increases the number of CFU-GM generated by ex vivo expansion of
      unmanipulated human MNCs and selected CD34+ cells.
AB  - BACKGROUND: Ex vivo expansion strategies with different cytokine combinations are
      currently used by several groups as a means of increasing the number of HPCs for
      a variety of special clinical applications. Because there is little information
      on the potential role of IL-10 in such ex vivo expansion models, the effect of
      this cytokine on the generation of myeloid progenitor cells in suspension
      cultures was investigated. STUDY DESIGN AND METHODS: On the basis of data from
      the literature and from new experiments, the combination of SCF and IL-3 at
      concentrations of 100 ng per mL and 100 U per mL, respectively, was chosen as the
      standard cocktail. The addition of IL-10 to such cultures resulted in a marked
      and dose-dependent potentiation of myeloid progenitor cell production. RESULTS:
      Using unmanipulated leukapheresis components from 13 individuals (including
      lymphoma and cancer patients and normal donors), the expansion multiple of CFU-GM
      after 14 days as compared with pre-expansion values was 9.54 +/- 2.31 times by
      SCF/IL-3 and 46.38 +/- 7.37 times by the combination of SCF/IL-3 and 100 ng per
      mL of IL-10 (p<0.001). IL-10 also potentiated CFU-GM generation from selected
      CD34 PBMNCs (n = 9) with an expansion of 17.22 +/- 7.04 times versus 45.67 +/-
      16.78 times using the SCF/IL-3 and SCF/IL-3/IL-10 combination, respectively
      (p<0.05). Moreover, expansion-promoting effects of IL-10 were observed in liquid
      cultures containing MNCs from bone marrow (n = 4) and cord blood (n = 3), but did
      not reach statistical significance because of the small number of samples.
      CONCLUSION: These results suggest IL-10 as a useful cytokine to optimize
      progenitor cell-expansion strategies for clinical application.

PMID- 11346704
TI  - Uncontrolled-rate freezing and storage at -80 degrees C, with only 3.5-percent
      DMSO in cryoprotective solution for 109 autologous peripheral blood progenitor
      cell transplantations.
AB  - BACKGROUND: Although controlled-rate freezing and storage in liquid nitrogen are
      the standard procedure for peripheral blood progenitor cell (PBPC)
      cryopreservation, uncontrolled-rate freezing and storage at -80 degrees C have
      been reported. STUDY DESIGN AND METHODS: The prospective evaluation of 109
      autologous PBPC transplantations after uncontrolled-rate freezing and storage at 
      80 degrees C of apheresis products is reported. The cryoprotectant solution
      contained final concentrations of 1-percent human serum albumin, 2.5-percent
      hydroxyethyl starch, and 3.5-percent DMSO. RESULTS: With in vitro assays, the
      median recoveries of nucleated cells (NCs), CD34+ cells, CFU-GM, and BFU-E were
      60.8 percent (range, 11.2-107.1%), 79.6 percent (6.3-158.1%), 35.6 percent (0.3
      149.5%), and 32.6 percent (1.7-151.1%), respectively. The median length of
      storage was 7 weeks (range, 1-98). The median cell dose, per kg of body weight,
      given to patients after the preparative regimen was 6.34 x 10(8) NCs (range, 0.02
      38.3), 3.77 x 10(6) CD34+ cells (0.23-58.5), and 66.04 x 10(4) CFU-GM (1.38
      405.7). The median time to reach 0.5 x 10(9) granulocytes per L, 20 x 10(9)
      platelets per L, and 50 x 10(9) reticulocytes per L was 11 (range, 0-37), 11 (0
      129), and 17 (0-200) days, respectively. Hematopoietic reconstitution did not
      differ in patients undergoing myeloablative or nonmyeloablative conditioning
      regimens before transplantation. CONCLUSION: This simple and less expensive
      cryopreservation procedure can produce successful engraftment, comparable to that
      obtained with the standard storage procedure.

PMID- 11346705
TI  - Peripheral blood progenitor cell collection after epirubicin, paclitaxel, and
      cisplatin combination chemotherapy using EPO-based cytokine regimens: a
      randomized comparison of G-CSF and sequential GM-/G-CSF.
AB  - BACKGROUND: The peripheral blood progenitor cell (PBPC) mobilization capacity of
      EPO in association with either G-CSF or sequential GM-CSF/G-CSF was compared in a
      randomized fashion after epirubicin, paclitaxel, and cisplatin (ETP)
      chemotherapy. STUDY DESIGN AND METHODS: Forty patients with stage IIIB, IIIC, or
      IV ovarian carcinoma were enrolled in this randomized comparison of mobilizing
      capacity and myelopoietic effects of G-CSF + EPO and GM-/G-CSF + EPO following
      the first ETP chemotherapy treatment. After ETP chemotherapy (Day 1), 20 patients
      received G-CSF 5 microg per kg per day from Day 2 to Day 13 and 20 patients
      received GM-CSF 5 microg per kg per day from Day 2 to Day 6 followed by G-CSF 5
      microg per kg per day from Day 7 to Day 13. EPO (150 IU per kg) was given every
      other day from Day 2 to Day 13 to all patients in both arms of the study.
      Apheresis (two blood volumes) was performed during hematologic recovery. RESULTS:
      The magnitude of CD34+ cell mobilization and the abrogation of patients'
      myelosuppression were comparable in both study arms; however, GM-/G-CSF + EPO
      patients had significantly higher CD34+ yields because of a higher CD34+ cell
      collection efficiency (57.5% for GM-/G-CSF + EPO and 46.3% for G-CSF + EPO
      patients; p = 0.0009). Identical doses of PBPCs mobilized by GM-/G-CSF + EPO and
      G-CSF + EPO drove comparable hematopoietic recovery after reinfusion in patients
      treated with identical high-dose chemotherapy. CONCLUSION: The sequential
      administration of GM-CSF and G-CSF in combination with EPO is feasible and
      improves the PBPC collection efficiency after platinum-based intensive
      polychemotherapy, associating high PBPC mobilization to high collection
      efficiency during apheresis.

PMID- 11346706
TI  - Kinetics of PBPC mobilization by cyclophosphamide, as compared with that by
      epirubicin/paclitaxel followed by G-CSF support: implications for optimal timing
      of PBPC harvest.
AB  - BACKGROUND: Limited information is available on the mobilization kinetics of
      autologous PBPCs after induction with various chemotherapy regimens. With PBPC
      mobilization in patients with breast cancer used as a model for chemotherapy
      induced PBPC recruitment, the kinetics of progenitor cells mobilized either with
      cyclophosphamide (CY) or epirubicin/paclitaxel (EPI-TAX) followed by the
      administration of G-CSF was compared. STUDY DESIGN AND METHODS: The study
      included a total of 86 patients with breast cancer (stage II-IV) receiving either
      CY (n = 39) or EPI-TAX (n = 47), both followed by G-CSF support. The progenitor
      cell content in peripheral blood and apheresis components was monitored by flow
      cytometric enumeration of CD34+ cells. PBPC collection was started when the
      threshold of >20 x 10(6) CD34+ cells per L of peripheral blood was reached.
      RESULTS: The PBPC collection was begun a median of 9 days after the
      administration of EPI-TAX followed by G-CSF support, as compared to a median of
      13 days after mobilization with CY plus G-CSF. After treatment with CY, the total
      numbers of PBPCs peaked on Day 1 of apheresis, and they rapidly declined
      thereafter. In contrast, treatment with EPI-TAX followed by G-CSF administration
      led to a steady mobilization of CD34+ cells during leukapheresis. The difference
      in the mobilization patterns with CY and EPI-TAX resulted in a greater yield of
      CD34+ cells per L of processed blood volume. Compared to EPI-TAX, mobilization
      with CY required the overall processing of 30 percent less whole-blood volume to
      reach the target yield of > or = 10 x 10(6) CD34+ cells per kg of body weight.
      After a median of three apheresis procedures, however, both CY+G-CSF and EPI
      TAX+G-CSF were equally effective in obtaining this target yield. CONCLUSION:
      These results imply that specific PBPC mobilization as part of a given
      chemotherapy regimen should be taken into consideration before the planning of a
      PBPC harvest.

PMID- 11346707
TI  - MHC-peptide multimers: tools of choice for detecting and sorting antigen-specific
      T-cells.

PMID- 11346708
TI  - Universal WBC reduction: the case for and against.

PMID- 11346710
TI  - The myth of the ultimate blood safety wall.

PMID- 11346709
TI  - Selective transfusion protocols: errors and accidents waiting to happen.

PMID- 11346711
TI  - The role of WBC adhesion molecules in WBC removal during filtration.

PMID- 11346712
TI  - Comparison of different serum-free media for ex vivo expansion of HPCs from cord
      blood using thrombopoietin, Flt-3 ligand, IL-6, and IL-11.

PMID- 11346713
TI  - [Calcitriol increases burst forming unit-erythroid (BFU-E) in vitro proliferation
      in chronic uremia. Synergic effect with DNA recombinant erythropoietin (rHu
      Epo)].
AB  - BACKGROUND: It has been suggested that calcitriol (C) could improve anemia in
      chronic renal failure. However it remains debatable whether vitamin D has a
      specific effect on erythropoiesis, or it acts via suppression of
      hyperparathyroidism. METHODS: We enrolled 29 patients with chronic renal failure,
      free from malignancies, iron deficiency or other chronic or hematological
      diseases. Aluminium accumulation was also excluded by DFO test. 22 were on
      hemodialysis and 7 on conservative management, creatinine clearance ranging 22-48
      ml/min. Their mean age was 62+/-28 years and duration of renal disease was 98+/
      51 months. No patient under-went rHu-Epo or Vitamin D treatment. 4 subjects were
      enrolled as controls. Samples of peripheral blood were drawn for the Burst
      Forming Unit-Erythroid (BFU-E) assay. After isolation of mononuclear cells by
      density gradient centrifugation with Fycoll-Hypaque, a 15-day incubation was set
      up with four different conditions: a) adding standard dose, 3 U/ml, of r-HuEpo
      (Dompe Biotec), standard colture; b) combined doses of r-HuEpo, 3 U/ml, and C
      (Abbott), 30 pg; c) standard dose, 3 U/ml, of r-HuEpo and high dose, 300 pg, of
      C; and lastly d) combined high doses of r-HuEpo, 30 U/ml, and C, 300 pg. RESULTS:
      In the b colture (combined low doses) a higher BFU-E proliferation was found vs
      standard (a) colture (33.2+/-15.5 vs 17.1+/-9.2, p<0.02); interestingly, either
      in the c and d studies BFU-E showed an even higher proliferation (52.3+/-24 and
      86.3+/-37.8 respectively, p<0.01 vs a). No difference was found when evaluating
      separately preterminal and hemodialysis patients. In control subjects only
      colture d showed an increased BFU-E proliferation. CONCLUSIONS: C has a direct
      effect on erythroid precursors proliferation in vitro, acting in a sinergystic
      manner with rHuEpo. C may be useful as adjuvant therapy for renal anemia.

PMID- 11346714
TI  - [Long-term therapy of benign prostatic hyperplasia. Our experience].
AB  - BACKGROUND: In order to evaluate the benefit of long-term medical treatment (4
      years) in benign prostatic hyperplasia in June 1992 we prospectively started a
      not randomized study in selected benign prostatic hyperplasia patients for whom
      surgery was not indicated because of high surgical or post-surgical risk, or when
      they refused the intervention. METHODS: We included in the study 239 outpatients;
      118 of them were affected by concomitant cardiovascular illness, 37 by neurologic
      diseases, 29 by neoplastic diseases and 55 refused surgery for the possible
      general or specific complications like retrograde ejaculation. All subjects have
      been checked every six months by transabdominal ultrasonography of the urinary
      tract, evaluation of the prostate volume and percent of post-micturitional
      residue, associated with uroflussometry. The patients have been divided into
      three groups and treated by finasteride, mepartricin, alfuzosin, doxazosin. The
      enlistment concluded in December 1995 and the follow-up extended up to December
      1999. RESULTS: Our data clinically and statistically allow to confirm the
      validity of drug therapy for benign prostatic hyperplasia, not only in selected
      patients with high surgical risk, but also in subjects without a significant
      morbidity. CONCLUSIONS: In these patients, drug therapy may resolve the
      pathology, or allow the use of minimally invasive surgery (i.e. lasertherapy,
      transuretheral incision, etc.).

PMID- 11346715
TI  - [Mepartricin in the treatment of male pelvic pain syndrome secondary to chronic
      nonbacterial prostatitis/prostatodynia].
AB  - BACKGROUND: The aim of this paper is to compare the activity of mepartricin vs
      placebo in male pain pelvic syndrome secondary to chronic nonbacterial
      prostatitis/prostatodynia. METHODS: Forty-two patients have been tested (mean
      age: 35 years; range 29-44), these proved affected by male pain pelvic syndrome
      secondary to chronic nonbacterial prostatitis/prostatodynia, and were randomized
      into 2 groups: the 1st treated with mepartricin 40 mg/die for 60 days, the 2nd
      with placebo (C vitamin 500 mg/die) for 60 days. The following patterns were
      examined: spontaneous and rectal examination pain, diurnal and nocturnal urinary
      frequency and prostatic volume. Side effects in course of therapy were examined
      as well. RESULTS: Mepartricin proved significantly more active than placebo in
      reducing spontaneous pain, rectal examination pain, diurnal urinary frequency,
      nicturia and prostatic volume. No significant difference proved to emerge between
      placebo and mepartricin in terms of side effects. CONCLUSIONS: These data allow
      us to substain that mepartricin may be a useful and safe drug for the therapy of
      male pain pelvic syndrome secondary to chronic nonbacterial
      prostatitis/prostatodynia.

PMID- 11346716
TI  - Iatrogenic ejaculation disorders and their prevention.
AB  - Ejaculation is mediated by sympathetic fibers originating from the D10-L2
      medullar center. These nerves rise from the lumbar ganglia of the paravertebral
      sympathetic trunk and travel posteriorly to the vena cava and then to the
      interaortocaval space, on the right side, and laterally to the aorta, on the left
      side. They are the principal constituents of the superior hypogastric plexus.
      Many surgical operations can cause an ejaculation disorder, but the most
      important is retroperitoneal lymphadenectomy (RL) for testis cancer, because it
      involves young patients and it has been the subject of important researches in
      order to perform lymph node dissection without ejaculation loss (unilateral
      lymphadenectomy and nerve sparing lymphadenectomy). Our experience concerns 41
      patients who underwent RL for testis cancer from 1983 to 1998. Survival rate was
      95.2% (mean follow up 64 months). RL was performed bilaterally in 14 patients.
      Two of them died of metastases within 2 years after the operation. Ejaculation
      was maintained in only 4 of the 12 surviving patients (33%). All the 17 patients
      (100%) underwent right monolateral RL and 7 of the 10 (70%) underwent left
      monolateral RL preserved ejaculation. The anatomosurgical concepts of the RL
      sparing the ejaculation can be adopted in other retroperitoneal surgical
      operations that can produce ejaculation disorders, such as wide lymphadenectomy
      for renal cell carcinoma or tumors of the upper urinary tract, exeresis of pre-
      aortic tumors, exeresis or disjunction of horseshoe kidney and aorto-iliac
      revascularization. Surgical therapy of benign prostatic hyperplasia (BPH) (open
      surgery or transurethral prostatic resection) is associated with retrograde
      ejaculation in nearly 100% of cases. The mechanism of the dysfunction is clear,
      if following the procedure the bladder neck remains opened. Loss of ejaculation
      is reported in variable percentage after the newer endoscopic techniques for the
      treatment of BPH. Transurethral needle ablation (TUNA) seems to have the lower
      risk of retrograde ejaculation. Retrograde ejaculation can also be related to a
      traumatic injury of the posterior urethra, because of the trauma itself or the
      therapy. Finally, the ejaculation disorder can be produced by several drugs that
      block, as a main or secondary effect, the alpha-adrenoreceptors or act at the
      central level. This side effect has to be kept in mind when these drugs are used
      in young or sexually active patients.

PMID- 11346717
TI  - [Unusual case of inverted papilloma in a fibro-epithelial polyp of the ureter].
AB  - Inverted papilloma of the upper urinary tract is a rare lesion and the
      differential diagnosis with transitional cell carcinoma is really hard. A case of
      49 year-old male with recurrent right flank pain is reported. Excretory urogram
      suggested a filling defect involving the right mid ureter and bilateral
      retrograde pyelogram that confirmed a solitary filling defect in the right mid
      ureter, while selective urinary cytology was positive for transitional cell
      carcinoma G1. Conservative therapy was carried out and 2 years follow-up with
      several excretory urograms and ultrasound studies revealed no recurrence.

PMID- 11346718
TI  - [Inflammatory pseudomotor of the bladder. A diagnostic and therapeutic dilemma].
AB  - Inflammatory pseudotumor is a reactive benign lesion which can be very difficult
      to distinguish from some malignant bladder tumors like sarcomas or sarcomatoid
      carcinoma. The aim of this study was to present a new case of inflammatory
      pseudotumor and to review the present diagnostic and therapeutic criteria for
      this lesion. A 72-year-old female was admitted to the emergency room due to
      important hematuria. Transurethral resection of a bladder tumor located in the
      left lateral wall was performed. Pathologic studies were suggestive of
      inflammatory pseudotumor, but a mixoid leiomyosarcoma couldn t be completely
      discarded and a partial cystectomy with ipsilateral lymphadenectomy were carried
      out. Immunohistochemical studies were positive for vimentin, desmin, smooth
      muscle actin and cytoqueratins while epithelial membrane antigen and S-100
      protein were negative. The patient is disease free after a year follow-up. When
      diagnosis is certain, complete transurethral resection is the treatment of
      choice. However, if there is no total pathologic confirmation, if it is a very
      wide lesion or if it is recurring after endoscopic resection, a partial
      cystectomy is suggested.

PMID- 11346719
TI  - [Use of sildenafil in the chronic uremic patient].
AB  - BACKGROUND: Erectile dysfunction is one of the factors influencing negatively the
      quality of life of patients in hemodialytic treatment. The international
      literature shows that erectile dysfunction is present in 30% of patients with
      chronic renal failure and in 50% of patients undergoing dialytic treatment.
      Fertility, libido and erectile dysfunction, suffer progressive worsening with
      time, in spite of hemodialysis. The availability of a drug like Sildenafil can
      improve the quality of life of the patient and give him a normal sexual activity.
      METHODS: Twenty patients between 29 and 51 years, were selected; 2 of these had
      been subjected to renal transplant, with a dialytic treatment time varying from 3
      to 13 years. Before the treatment all the patients have been subjected to an
      andrological screening (testosterone, prolactin, penile color Doppler ultrasound)
      and proposed the IIEF test. Therapeutic strategy included the assumption of the
      drug in the days in which the patients were not subjected to dialysis, with an
      interval from 1 to 3 weeks between assumption and another. The dose was 25-50 mg.
      At the end of three months of therapy the patients were again subjected to the
      IIEF test. RESULTS: All patients reported an improvement in sexual activity and
      sexual desire with very good repercussions on general and psychophysical
      conditions. CONCLUSIONS: The results demonstrate at least that Sildenafil is also
      effective in uremic patients in dialytic treatment or after renal transplant and
      that it can therefore resolve one of the main problems for the normal development
      of the life of such patients.

PMID- 11346720
TI  - [Bright disease in Turin and Italy from the middle of the 19th century to the
      middle of the 20th century].
AB  - For many years the term  nephritis  was used to indicate  renal diseases  (in the
      sense of Bright s disease) in a larger sense. This review summarizes the history
      of the concept of  glolomerulonephritis  from Egyptian Medicine up to the Post
      Biopsy Era, in particularly in Turin and in Italy. This study reports an
      epidemiology survey of Bright s disease in Italy from 1880 up to 1960. Towards
      the end of the 19th century Bright s disease accounted for 26 deaths/year/105
      population (in comparison with more than 200 from tubercolosis) in Italy. At the
      beginning of the 20th century, Bright s disease was the seventh cause of death in
      Italy. Moreover, in Italy autopsy studies showed a higher percentage of deaths
      attributed to Bright s disease (5-7%) in comparison with those obtained from
      vital studies. In 1960, just before the beginning of renal replacement therapy,
      Bright s disease accounted for 15.7 deaths/year/105 population. Probably it was
      difficult to recognize in the real incidence of chronic renal diseases leading to
      death in the 1960s, and vital studies were able to furnish only approximate
      estimates. However, noteworthy is the fact that these values were very close to
      those estimated as being the annual need for renal replacement therapy (10
      20/year/105 population).

PMID- 11346721
TI  - Is it ethical not to...?

PMID- 11346722
TI  - It's time to modernize our approach to oral HPV lesions.

PMID- 11346725
TI  - Effects of antimicrobial agents.

PMID- 11346727
TI  - Review of systemic lupus erythematosus.

PMID- 11346726
TI  - Parameters of radiologic care: An official report of the American Academy of Oral
      and Maxillofacial Radiology.
AB  - The American Academy of Oral and Maxillofacial Radiology developed these
      Parameters of Care to provide national guidelines for the use of radiographs
      prescribed for the diagnosis of disease, treatment planning, and follow-up care
      of patients with abnormalities of the oral and maxillofacial region. The
      Parameters cover radiographic techniques, imaging of the temporomandibular joint,
      imaging of diseases of the jaws, and imaging of dental implant sites.

PMID- 11346728
TI  - Matrix metalloproteinases in mild and severe temporomandibular joint internal
      derangement synovial fluid.
AB  - OBJECTIVES: The first objective of this study was to verify the presence of and
      identify the molecular forms of matrix metalloproteinases (MMPs), including
      collagenases (MMP-1, MMP-8, and MMP-13) and gelatinases (MMP-2 and MMP-9), in the
      synovial fluid (SF) of mild and severe temporomandibular joint internal
      derangement (TMJ-ID). Another objective was to evaluate whether the SF MMPs are
      potential diagnostic markers that reflect the stage of intra-articular
      inflammation in the TMJ. STUDY DESIGN: The subjects were 44 patients with mild (n
      = 16) or severe (n = 28) TMJ-ID; they were classified on the basis of subjective
      symptoms, clinical and radiographic findings, and surgical observations. The
      patients were surgically treated, and SF samples were collected immediately
      before the operation. The collagenase activity of SF samples was analyzed by
      means of a type I collagen degradation assay. The levels and molecular forms of
      the SF MMPs as well as the tissue inhibitors of MMPs (TIMP-1 and TIMP-2) were
      analyzed with Western immunoblotting and gelatin zymography. RESULTS: The SF of
      both the mild and the severe TMJ-ID patients exhibited free collagenase activity
      and activity capable of further degrading the (3/4)(alphaA) fragments. Ninety-two
      kilodalton proMMP-9 and its 121-kD complex form, as well as 72-kD proMMP-2 were
      significantly increased in the mild TMJ-ID group (P <.05 in all cases). Both 70-
      to 80-kD neutrophil type and 45- to 55-kD mesenchymal cell-type MMP-8
      (corresponding to the latent and active forms) were observed in mild and severe
      TMJ-ID SF, but they predominated in mild TMJ-ID. Both MMP-1 and MMP-13 were
      observed in both groups, and in mild TMJ-ID SF the low-molecular weight forms of
      MMP-1 indicated activation of the enzyme. CONCLUSIONS: The degradation of type I
      collagen in the TMJ is evidently due to the collective action of many
      collagenolytic MMPs present in the SF of patients with mild and severe TMJ-ID.
      The elevated levels of MMP-2, MMP-9, and MMP-8 in the SF of patients with mild
      TMJ-ID eventually reflect the active phase of TMJ destruction. These observations
      may have considerable diagnostic and therapeutic significance in the management
      of TMJ disorders.

PMID- 11346729
TI  - Hemodynamic assessment of local anesthetic administration by laser Doppler
      flowmetry.
AB  - OBJECTIVE: The hemodynamic effects of local anesthetic administration with and
      without a vasoconstrictor were compared by using laser Doppler flowmetry. STUDY
      DESIGN: Seventeen people participated in a single study session in which they
      were given 2 intraoral injections. The injections, which were administered in
      random order, consisted of 1.8 mL lidocaine (2%) with epinephrine (1:100,000) and
      mepivacaine (3%). Hemodynamic parameters consisting of blood pressure, heart
      rate, and laser Doppler flowmetry were reordered at regular intervals. RESULTS:
      The laser Doppler flowmeter detected changes in the peripheral perfusion of the
      finger that were not detected by changes in blood pressure and heart rate. The
      greatest change was associated with anxiety and occurred just before the
      injection. The inclusion of epinephrine in the local anesthetic resulted in a
      persistence of these changes. CONCLUSION: This investigation has confirmed the
      sensitivity of laser Doppler flowmetry as an investigational tool for assessing
      hemodynamic changes associated with anxiety and the administration of local
      anesthesia.

PMID- 11346730
TI  - Characteristics of patients complaining of halitosis and the usefulness of gas
      chromatography for diagnosing halitosis.
AB  - OBJECTIVE: The purpose of this study was to examine the characteristics of
      patients complaining of halitosis and to evaluate the diagnostic accuracy of 3
      methods of measuring halitosis. STUDY DESIGN: The actual degree of halitosis was
      determined through use of an organoleptic test in 155 patients aged 46 +/- 17
      years (mean +/- SD). The volatile sulfur compounds (VSCs) were determined with
      gas chromatography and with sulfide monitoring. RESULTS: The organoleptic test
      revealed that 55% of the subjects had either no mouth odor or slight mouth odor.
      There was a significant correlation between the organoleptic score and the total
      VSC level as determined through use of other methods. The critical discrimination
      value of the total VSC level was calculated to be 0.057 ppm for gas
      chromatography and 0.117 ppm for sulfide monitoring; high sensitivity and
      specificity were obtained when the gas chromatography value was used. The amount
      of tongue coating was significantly greater in the halitosis-positive group than
      in the halitosis-negative group, whereas there was no difference in salivary flow
      rate between the 2 groups. CONCLUSION: These results indicate that determining
      VSCs with gas chromatography is a useful means of diagnosing halitosis.

PMID- 11346731
TI  - Reliability of toluidine blue application in the detection of oral epithelial
      dysplasia and in situ and invasive squamous cell carcinomas.
AB  - OBJECTIVE: The objective of this study was to evaluate the reliability of in vivo
      staining with toluidine blue in the detection of oral epithelial dysplasia, in
      situ carcinoma, and invasive squamous cell carcinomas in potentially malignant
      epithelial lesions (PMELs) and superficial oral ulcerations suggesting
      malignancy. STUDY DESIGN: Fifty patients with PMELs and superficial oral
      ulcerations suggestive of malignancy were selected from those treated at the Oral
      Medicine Service, Faculty of Dentistry, Araraquara, Brazil. All lesions were
      submitted to staining with an aqueous solution of 1% toluidine blue, followed by
      biopsy and histologic analysis. The sensitivity, specificity, and positive and
      negative predictive values were calculated. RESULTS: Histologic diagnosis
      revealed that 14% of the lesions analyzed were in situ carcinoma and invasive
      squamous cell carcinomas, 12% were epithelial dysplasias, 13% were keratosis, 40%
      were lichen planus, and 8% were other benign lesions. The sensitivity of the
      staining was 77%, the specificity 67%, and the positive and negative predictive
      values 43.5% and 88.9%, respectively. CONCLUSIONS: Staining with toluidine blue
      was demonstrated to be highly reliable in the detection of in situ carcinoma and
      invasive squamous cell carcinoma, because false-negative results for the lesions
      did not occur. Toluidine blue staining is an adjunct to clinical judgment and not
      a substitute for either judgment or biopsy.

PMID- 11346732
TI  - Unstimulated salivary flow rates of young children.
AB  - OBJECTIVE: Studies on salivary flow rates in human beings have mainly been
      carried out with adults. The purpose of this study was to determine the
      unstimulated salivary flow rates of children 4 to 7 years old. In addition, the
      relative contributions of the variables age, gender, race, height, body weight,
      dentition status, use of prescription medication, and health status (information
      obtained from parents) to the unstimulated salivary flow rates of children were
      also studied. STUDY DESIGN: Data were obtained from children (n = 447) at 2 sites
      in the United States (site 1, southeast Michigan; site 2, northern Michigan) and
      at 5 sites in Brazil (site 3, Porto Alegre; site 4, Sao Paulo; site 5, Belem; and
      sites 6 and 7, sites in Rio de Janeiro). In northern Michigan (site 2) the
      participants were cognitively or developmentally disabled, or both. In Rio de
      Janeiro (site 7), a group of 8- to 12-year-olds served as a control group. Saliva
      samples were collected for 3 minutes between 9 AM and noon in the spring or
      summer, and the saliva rate was determined gravimetrically. Data were analyzed by
      analysis of variance, bivariate analysis, and regression analysis. RESULTS: The
      secretion rates at the 7 sites were (in milliliters per minute) 0.19 +/- 0.15,
      0.23 +/- 0.28, 0.34 +/- 0.23, 0.48 +/- 0.37, 0.25 +/- 0.27, 0.37 +/- 0.28, and
      0.61 +/- 0.34, respectively. There were significant differences among sites (P
      <.0001). The older group (site 7) had flow rates that were significantly higher
      than the flow rates of any other group. In addition, children from Michigan
      (sites 1 and 2) had significantly lower rates than most groups of children in
      Brazil. Girls had lower unstimulated salivary flow rates than boys did at all the
      sites, but the differences were not statistically significant. Race was shown not
      to affect the flow rates. The use of any prescription medication by children in
      the previous 3 months was associated with lower salivary flow rates than were
      found in children not using prescription medication. Children who were in good
      health and who had no previous medical conditions had higher flow rates--but not
      significantly so. Higher flow rates occurred in children with mixed dentition
      than in children with primary dentition, although again the differences were not
      statistically significant. Regression analysis revealed weight to be of
      significance in explaining the variability of the unstimulated salivary flow
      rates at 2 sites, height at 1 site, the use of prescription medication at 2
      sites, and age at 1 site. CONCLUSIONS: The unstimulated salivary flow rates in
      children in the northern United States are comparable with those reported for
      Japanese children, whereas the flow rates of children in Brazil are comparable
      with those reported for North American and European adults. In addition, none of
      the demographic variables/parameters tested contributed consistently to the
      variability of the unstimulated salivary flow rates in children at the 7 sites
      assessed in this study.

PMID- 11346733
TI  - Gender differences in human immunodeficiency virus-related oral lesions: an
      Italian study.
AB  - OBJECTIVE: The purpose of this study was to investigate the relationship between
      oral lesions and gender, age, CD4(+) cell count, human immunodeficiency virus-1
      (HIV-1) viral load, antiretroviral therapy, and route of transmission in a group
      of HIV-infected (HIV+) persons from the Mediterranean region. STUDY DESIGN: The
      participants in this study were HIV+ adults who sought dental care between
      January 1999 and June 1999 in the Department of Oral Medicine (University of
      Palermo, Italy). RESULTS: One hundred thirty-six HIV+ adults came in for an
      initial oral examination. Their mean age was 35.2 years (SD +/- 7.97), and 33%
      were women. Their mean CD4(+) cell count was 325.3 x 10(6) /L (SD +/- 225.8), and
      their HIV-1 viral load was 39,168.3 copies/mL (SD +/- 144,256.1). Oral lesions
      were found in 47% of the study group, as well as in 56.5% of women (n = 46)
      versus 45.5% of men (n = 90; P =.05). Oral candidiasis was the most common
      disease; it is significantly associated with women (P =.004), CD4(+) cell count
      (P =.005), and HIV-1 viral load (P =.0003). No significant relationships were
      found between any types of oral lesions and age, antiretroviral therapy, or route
      of transmission (P >.2). CONCLUSION: The prevalence of HIV-related oral lesions
      was significantly higher in women than in men, especially for oral candidiasis,
      the most common lesion observed related to immune status and HIV-1 viral load.

PMID- 11346734
TI  - Oral recurrent human herpes virus infection and bone marrow transplantation
      survival.
AB  - OBJECTIVE: This study was conducted to compare the survival rates of bone marrow
      transplantation (BMT) patients who were affected with the survival rates of those
      who were not affected by oral recrudescent human herpes virus-1 infection (HHV-1)
      after transplantation. STUDY DESIGN: Fifty-two consecutive patients who underwent
      BMT were included in the study. The time of death after BMT was displayed, by
      means of the Kaplan-Meier method, for the following parameters: age and gender of
      the patient, donor gender, primary disease, stem cells, conditioning regimen,
      platelet number after day 100, acute and chronic graft-versus-host disease, oral
      recurrent HHV-1 infection post-BMT, oral lichenoid lesions of graft-versus-host
      disease, graft-versus-host disease at the salivary glands, parenteral nutrition,
      and oral mucositis. The data were initially analyzed by means of the log-rank
      test and then included in the Cox proportional hazards model. RESULTS: The
      multivariate analysis demonstrated a significance of 5% for only the platelet
      numbers and oral recurrent HHV-1 infection. CONCLUSION: The present study
      provides evidence that platelet numbers below 100,000 cells/mm(3) after day 100
      and oral recurrent HHV-1 infection are independent negative prognostic variables
      in BMT patients' 24-month survival rates.

PMID- 11346735
TI  - Growth characteristics of ameloblastoma involving the inferior alveolar nerve: a
      clinical and histopathologic study.
AB  - OBJECTIVE: Growth characteristics of ameloblastomas involving the inferior
      alveolar nerve were examined to determine the most appropriate surgical
      management of the nerve at the time of the surgical procedure. STUDY DESIGN:
      Clinical and histopathologic examinations were performed on 22 resected mandibles
      in which the inferior alveolar nerve was lying adjacent to, or contained within,
      the tumor. RESULTS: Patterns of tumor involvement of the nerve bundle were
      evaluated with respect to the presence of bone (11 patients) or connective tissue
      wall (7 patients) between the tumor and the nerve bundle, and tumor infiltration
      of perineural connective tissue (4 patients). Neither invasion into the nerve
      sheath nor invasion into the nerve itself by the ameloblastoma was detected.
      Tumor infiltration of the tissue surrounding the nerve was identified for the
      multicystic and solid types but not for the unicystic type. Presence of bone or
      connective tissue wall between the tumor and the nerve bundle was dominant in the
      unicystic and plexiform ameloblastomas, whereas tumor infiltration of the
      perineural tissue was frequently observed in ameloblastomas with the follicular
      pattern. CONCLUSION: The preservation of the inferior alveolar nerve may be
      possible in the management of the unicystic type of ameloblastoma. However, a
      more radical approach is necessary for treatment of multicystic or solid tumors,
      especially those exhibiting a follicular pattern.

PMID- 11346736
TI  - Basaloid squamous carcinoma of the oral cavity: report of 2 cases and study of
      AgNOR, PCNA, p53, and MMP expression.
AB  - Basaloid squamous carcinoma (BSC) is an uncommon aggressive variant of squamous
      cell carcinoma (SCC) with a predilection for the head and neck. In the English
      literature, approximately 40 cases of BSC in the oral cavity have been described.
      In this study, the clinicopathologic features of 2 cases of BSC affecting the
      buccal mucosa are reported. In addition, we compare the proliferative and
      invasive potential of BSC cells with that of poorly differentiated SCC cells
      matched for age, sex, site, and TNM status. Proliferative activity was studied
      through use of the argyrophilic nuclear organizer region (AgNOR) method and
      immunohistochemical quantification of proliferating cell nuclear antigen (PCNA).
      The invasive potential was evaluated through use of the semiquantitative reverse
      transcriptase-polymerase chain reaction (RT-PCR) for matrix metalloproteinases
      (MMPs). Alterations of p53 were also investigated through use of
      immunohistochemistry. The tumors showed many clinical and histopathologic
      similarities to tumors in cases previously reported. The AgNOR and PCNA indices
      were significantly higher in the 2 cases of BSC than in the cases of SCC.
      Immunostaining for p53 protein showed a higher percentage of positive cells and
      more intense staining in the BSC tissues than in the SCC tissues. RT-PCR studies
      clearly demonstrated that the expression of MMP-1, MMP-2, and MMP-9 was higher in
      cells from BSCs than in cells from SCCs. Taken together, the data described here
      are compatible with the concept that BSC has a more aggressive biologic behavior
      than conventional SCC.

PMID- 11346737
TI  - A review of osteoblastoma and case report of metachronous osteoblastoma and
      unicystic ameloblastoma.
AB  - A case is reported of a young woman who, within a 2-year period, was diagnosed
      with an osteoblastoma at the apex of a maxillary molar and with a plexiform
      unicystic ameloblastoma in the posterior mandible. Previous cases of
      osteoblastoma occurring in the jaws are reviewed.

PMID- 11346738
TI  - Ameloblastoma with mucous cell differentiation.
AB  - The finding of pale or clear cells in ameloblastomas is an exceptionally rare-
      but not unreported--phenomenon. The diagnostic implications of the presence of
      such cells in ameloblastomas are several and relate mainly to the question of
      histopathologic differential diagnosis. Although mucous cells in ameloblastomas
      are an accepted phenomenon, their occurrence has been reported only infrequently.
      This report describes a case of ameloblastoma exhibiting histopathologic evidence
      of focal mucous cell differentiation. Issues relating to the differential
      diagnosis of this lesion are discussed.

PMID- 11346739
TI  - Bacteria isolated after unsuccessful endodontic treatment in a North American
      population.
AB  - OBJECTIVE: The purpose of this study was to determine the composition of the
      microbial flora present in teeth after the failure of root canal therapy in a
      North American population. These results were then compared with those of the
      previous Scandinavian studies. STUDY DESIGN: Fifty-four root-filled teeth with
      persistent periapical radiolucencies were selected for retreatment. After removal
      of the root-filling material, the canals were sampled with paper points, and by
      reaming of the apical dentin. Both samples were grown under aerobic and strict
      anaerobic conditions. Then the bacterial growth was analyzed. RESULTS: The
      microbial flora was mainly of 1 to 2 strains of predominantly gram-positive
      organisms. Enterococcus faecalis was the most commonly recovered bacterial
      species. CONCLUSIONS: Bacteria were cultivated in 34 of the 54 teeth examined in
      the study. E faecalis was identified in 30% of the teeth with a positive culture.

PMID- 11346740
TI  - Determination of endotoxins in the vital pulp of human carious teeth: association
      with pulpal pain.
AB  - OBJECTIVES: The aims of this investigation were to determine the presence or
      absence of endotoxins in the pulp of symptomatic and symptom-free human carious
      teeth, to quantify the amount of endotoxins present, and to associate the
      presence of endotoxins with the acute pulpal pain. MATERIAL AND METHODS: Pulpal
      tissue was sampled from 28 single-rooted carious teeth (15 symptomatic, 13
      symptom-free) derived from 28 patients. Samples were also taken from the pulp of
      5 noncarious control teeth. During sampling an effort was made to collect an
      equal weight of pulpal tissue in all cases (approximately 8 mg). The extraction
      of endotoxins was performed with the use of phenol-water. The assay and
      quantitative determination of endotoxins was performed with the use of a limulus
      lysate test. The data were analyzed statistically by using the independent t
      test. RESULTS: Endotoxins were detected in pulpal tissues of all carious teeth in
      the symptomatic (mean average, 0.15773 ng/mL; SD = 0.045811) and symptom-free
      group (mean average, 0.10723 ng/mL; SD = 0.010925). In noncarious control teeth,
      endotoxins were not detected. The presence of endotoxins was significantly higher
      in the group of symptomatic teeth than in the group of symptom-free teeth (P
      <.001). CONCLUSIONS: The presence of endotoxins in the pulpal tissue of all the
      carious teeth indicates that they may play a major role in the pathogenesis of
      human pulpal diseases. Since a significantly higher level of endotoxins was
      detected in the pulp of symptomatic carious teeth than in that of symptom-free
      carious teeth, an association of endotoxins levels with severity of pulpal pain
      is probable.

PMID- 11346741
TI  - Accuracy of mandibular cross-sectional imaging with tuned- aperture computed
      tomography (TACT), iteratively reconstructed TACT, and multidirectional, linear,
      and transverse panoramic tomography.
AB  - OBJECTIVE: This study was designed to compare 5 modalities with respect to
      accuracy in mandibular cross-sectional imaging. The modalities tested were tuned
      aperture computed tomography (TACT), iteratively reconstructed TACT,
      multidirectional tomography, linear tomography, and transverse panoramic
      tomography. STUDY DESIGN: Twenty sites were selected from 3 dry human mandibles,
      and cross-sectional views were imaged through use of each of the 5 modalities. A
      quantitative analysis included measurements of 2 linear distances; a qualitative
      study included image evaluation by 6 observers. A nested mixed analysis of
      variance model was used to control for mandibles and locations within mandibles
      for the quantitative analysis; the Cochran-Mantel-Haenszel test was used for the
      qualitative analysis. RESULTS: There was a significant difference in measurement
      error for maximum height but not for width. There was also a significant
      difference in qualitative image evaluation results. CONCLUSIONS: Of the 5
      modalities tested, the narrow-layer multidirectional tomographic technique
      produced the greatest diagnostic accuracy and quality in cross-sectional imaging.
      The transverse panoramic tomographic technique produced the least diagnostic
      accuracy and quality. Linear tomography, TACT, and iteratively reconstructed TACT
      were intermediate in accuracy and quality.

PMID- 11346742
TI  - Condylar bony change, disk displacement, and signs and symptoms of TMJ disorders
      in orthognathic surgery patients.
AB  - OBJECTIVE: We sought to investigate the relationship between condylar bony change
      and disk displacement with respect to the signs and symptoms of temporomandibular
      joint (TMJ) disorders in patients undergoing orthognathic surgery. STUDY DESIGN:
      We performed a cross-sectional retrospective study of the pretreatment helical
      computed tomography scans of 129 orthognathic surgery patients. RESULTS: Condylar
      bony change, unilaterally or bilaterally, was found in 35.7% of the subjects and
      24.4% of the joints. Disk displacement, unilaterally or bilaterally, was seen in
      41.4% of the subjects and 29.5% of the joints. The type of craniofacial deformity
      was significantly associated with condylar bony change and disk displacement. No
      association of clinical symptoms with respect to craniofacial deformity, condylar
      bony change, or disk displacement was found except in the case of TMJ sounds.
      CONCLUSION: The results suggested that craniofacial deformity might be related to
      TMJ disorders, but the only clinical symptom associated with types of
      craniofacial deformity was TMJ sounds.

PMID- 11346743
TI  - Signal-to-noise ratios of 6 intraoral digital sensors.
AB  - OBJECTIVE: The objective of this study was to compare the signal-to-noise ratios
      (SNRs) of 6 intraoral direct digital sensors. The sensors were Visualix 1,
      Visualix 2, DenOptix, Computed Dental Radiography (CDR), CDR APS, and Digora.
      STUDY DESIGN: The sensors were exposed by using a dental x-ray machine operating
      at 50 kV, 8 mA and various exposure times. The phantom used was a hole measuring
      1 mm in diameter and 1.25 mm in depth, drilled in a 10-mm-thick aluminum block.
      Digital images were transferred as 8-bit tagged image file format files and
      analyzed by using a personal computer. RESULTS AND CONCLUSIONS: SNR values
      increased up to a maximum value at a certain exposure level and then, depending
      on the system, either decreased or maintained a high level with increased
      exposure. The Digora system produced the highest SNR values over a large exposure
      range, whereas the Visualix 2 and DenOptix systems produced the lowest SNR
      values. The 2 CDR sensors produced rather high SNRs but over a very small
      exposure range.

PMID- 11346744
TI  - Time for a bipartisan OTA.

PMID- 11346745
TI  - An end to procrastination?

PMID- 11346746
TI  - Stem-cell research in doubt as funders clash with government.

PMID- 11346749
TI  - Plans for missile defence system perturbs physicists.

PMID- 11346750
TI  - Dissent grows over Helmholtz proposals.

PMID- 11346752
TI  - Canada stakes claim on fusion energy project.

PMID- 11346753
TI  - Inquiry set up into Porton Down nerve-gas death.

PMID- 11346754
TI  - Europe brings experiments on chimpanzees to an end.

PMID- 11346757
TI  - Decisions, decisions...

PMID- 11346759
TI  - Science should help teach children the meaning of humanity.

PMID- 11346758
TI  - Private investigations.

PMID- 11346760
TI  - Particle physicists need a common objective.

PMID- 11346761
TI  - No campaign to strip Baltimore of his Nobel.

PMID- 11346762
TI  - How inbreeding affects productivity in Europe.

PMID- 11346763
TI  - Philanthropists are paying their dues.

PMID- 11346768
TI  - Floral tributes.

PMID- 11346769
TI  - A light and a dark side.

PMID- 11346770
TI  - Evolving ideas of brain evolution.

PMID- 11346771
TI  - Climate change. The Indonesian valve.

PMID- 11346772
TI  - Evolution. Developmental circuits rewired.

PMID- 11346773
TI  - Astronomy. Young stars go cruising by.

PMID- 11346774
TI  - Genomic stability. Hip-hopping out of control.

PMID- 11346776
TI  - Evolutionary genomics. Sex and the X.

PMID- 11346777
TI  - Earthquakes. Shock delay.

PMID- 11346778
TI  - Computational biology. Beyond the spherical cow.

PMID- 11346780
TI  - Spiny lobsters stick and slip to make sound.

PMID- 11346781
TI  - Plant development. Signals from mature to new leaves.

PMID- 11346782
TI  - Biogeology. How old are bacteria from the Permian age?

PMID- 11346784
TI  - Fisheries. Different behaviour of North and Irish Sea cod.

PMID- 11346785
TI  - Closing of the Indonesian seaway as a precursor to east African aridification
      around 3-4 million years ago.
AB  - Global climate change around 3-4 Myr ago is thought to have influenced the
      evolution of hominids, via the aridification of Africa, and may have been the
      precursor to Pleistocene glaciation about 2.75 Myr ago. Most explanations of
      these climatic events involve changes in circulation of the North Atlantic Ocean
      due to the closing of the Isthmus of Panama. Here we suggest, instead, that
      closure of the Indonesian seaway 3-4 Myr ago could be responsible for these
      climate changes, in particular the aridification of Africa. We use simple theory
      and results from an ocean circulation model to show that the northward
      displacement of New Guinea, about 5 Myr ago, may have switched the source of flow
      through Indonesia-from warm South Pacific to relatively cold North Pacific
      waters. This would have decreased sea surface temperatures in the Indian Ocean,
      leading to reduced rainfall over eastern Africa. We further suggest that the
      changes in the equatorial Pacific may have reduced atmospheric heat transport
      from the tropics to higher latitudes, stimulating global cooling and the eventual
      growth of ice sheets.

PMID- 11346786
TI  - Evidence for planet engulfment by the star HD82943.
AB  - Current models of the evolution of the known extrasolar planetary systems need to
      incorporate orbital migration and/or gravitational interactions among giant
      planets to explain the presence of large bodies close to their parent stars.
      These processes could also lead to planets being ingested by their parent stars,
      which would alter the relative abundances of elements heavier than helium in the
      stellar atmospheres. In particular, the abundance of the rare 6Li isotope, which
      is normally destroyed in the early evolution of solar-type stars but preserved
      intact in the atmospheres of giant planets, would be boosted substantially. 6Li
      has not hitherto been observed reliably in a metal-rich star, where metallicity
      refers to the total abundance of elements heavier than helium. Here we report the
      discovery of 6Li in the atmosphere of the metal-rich solar-type star HD82943,
      which is known to have an orbiting giant planet. The presence of 6Li can probably
      be interpreted as evidence for a planet (or planets) having been engulfed by the
      parent star.

PMID- 11346787
TI  - A complementarity experiment with an interferometer at the quantum-classical
      boundary.
AB  - To illustrate the quantum mechanical principle of complementarity, Bohr described
      an interferometer with a microscopic slit that records the particle's path.
      Recoil of the quantum slit causes it to become entangled with the particle,
      resulting in a kind of Einstein-Podolsky-Rosen pair. As the motion of the slit
      can be observed, the ambiguity of the particle's trajectory is lifted,
      suppressing interference effects. In contrast, the state of a sufficiently
      massive slit does not depend on the particle's path; hence, interference fringes
      are visible. Although many experiments illustrating various aspects of
      complementarity have been proposed and realized, none has addressed the quantum
      classical limit in the design of the interferometer. Here we report an
      experimental investigation of complementarity using an interferometer in which
      the properties of one of the beam-splitting elements can be tuned continuously
      from being effectively microscopic to macroscopic. Following a recent proposal,
      we use an atomic double-pulse Ramsey interferometer, in which microwave pulses
      act as beam-splitters for the quantum states of the atoms. One of the pulses is a
      coherent field stored in a cavity, comprising a small, adjustable mean photon
      number. The visibility of the interference fringes in the final atomic state
      probability increases with this photon number, illustrating the quantum to
      classical transition.

PMID- 11346788
TI  - Semiconducting non-molecular nitrogen up to 240 GPa and its low-pressure
      stability.
AB  - The triple bond of diatomic nitrogen has among the greatest binding energies of
      any molecule. At low temperatures and pressures, nitrogen forms a molecular
      crystal in which these strong bonds co-exist with weak van der Waals interactions
      between molecules, producing an insulator with a large band gap. As the pressure
      is raised on molecular crystals, intermolecular interactions increase and the
      molecules eventually dissociate to form monoatomic metallic solids, as was first
      predicted for hydrogen. Theory predicts that, in a pressure range between 50 and
      94 GPa, diatomic nitrogen can be transformed into a non-molecular framework or
      polymeric structure with potential use as a high-energy-density material. Here we
      show that the non-molecular phase of nitrogen is semiconducting up to at least
      240 GPa, at which pressure the energy gap has decreased to 0.4 eV. At 300 K, this
      transition from insulating to semiconducting behaviour starts at a pressure of
      approximately 140 GPa, but shifts to much higher pressure with decreasing
      temperature. The transition also exhibits remarkably large hysteresis with an
      equilibrium transition estimated to be near 100 GPa. Moreover, we have succeeded
      in recovering the non-molecular phase of nitrogen at ambient pressure (at
      temperatures below 100 K), which could be of importance for practical use.

PMID- 11346789
TI  - A prototype storage ring for neutral molecules.
AB  - The ability to cool and manipulate atoms with light has yielded atom
      interferometry, precision spectroscopy, Bose-Einstein condensates and atom
      lasers. The extension of controlled manipulation to molecules is expected to be
      similarly rewarding, but molecules are not as amenable to manipulation by light
      owing to a far more complex energy-level spectrum. However, time-varying electric
      and magnetic fields have been successfully used to control the position and
      velocity of ions, suggesting that these schemes can also be used to manipulate
      neutral particles having an electric or magnetic dipole moment. Although the
      forces exerted on neutral species are many orders of magnitude smaller than those
      exerted on ions, beams of neutral dipolar molecules have been successfully slowed
      down in a series of pulsed electric fields and subsequently loaded into an
      electrostatic trap. Here we extend the scheme to include a prototype
      electrostatic storage ring made of a hexapole torus with a circumference of 80
      cm. After injection, decelerated bunches of deuterated ammonia molecules, each
      containing about 106 molecules in a single quantum state and with a translational
      temperature of 10 mK, travel up to six times around the ring. Stochastic cooling
      might provide a means to increase the phase-space density of the stored molecules
      in the storage ring, and we expect this to open up new opportunities for
      molecular spectroscopy and studies of cold molecular collisions.

PMID- 11346790
TI  - Evidence against dust-mediated control of glacial-interglacial changes in
      atmospheric CO2.
AB  - The low concentration of atmospheric CO2 inferred to have been present during
      glacial periods is thought to have been partly caused by an increased supply of
      iron-bearing dust to the ocean surface. This is supported by a recent model that
      attributes half of the CO2 reduction during past glacial stages to iron
      stimulated uptake of CO2 by phytoplankton in the Southern Ocean. But atmospheric
      dust fluxes to the Southern Ocean, even in glacial periods, are thought to be
      relatively low and therefore it has been proposed that Southern Ocean
      productivity might be influenced by iron deposited elsewhere-for example, in the
      Northern Hemisphere-which is then transported south via ocean circulation
      (similar to the distal supply of iron to the equatorial Pacific Ocean). Here we
      examine the timing of dust fluxes to the North Atlantic Ocean, in relation to
      climate records from the Vostok ice core in Antarctica around the time of the
      penultimate deglaciation (about 130 kyr ago). Two main dust peaks occurred 155
      kyr and 130 kyr ago, but neither was associated with the CO2 rise recorded in the
      Vostok ice core. This mismatch, together with the low dust flux supplied to the
      Southern Ocean, suggests that dust-mediated iron fertilization of the Southern
      Ocean did not significantly influence atmospheric CO2 at the termination of the
      penultimate glaciation.

PMID- 11346791
TI  - Delayed triggering of the 1999 Hector Mine earthquake by viscoelastic stress
      transfer.
AB  - Stress changes in the crust due to an earthquake can hasten the failure of
      neighbouring faults and induce earthquake sequences in some cases. The 1999
      Hector Mine earthquake in southern California (magnitude 7.1) occurred only 20 km
      from, and 7 years after, the 1992 Landers earthquake (magnitude 7.3). This
      suggests that the Hector Mine earthquake was triggered in some fashion by the
      earlier event. But uncertainties in the slip distribution and rock friction
      properties associated with the Landers earthquake have led to widely varying
      estimates of both the magnitude and sign of the resulting stress change that
      would be induced at the location of the Hector Mine hypocentre-with estimates
      varying from -1.4 bar (ref. 6) to +0.5 bar (ref. 7). More importantly, coseismic
      stress changes alone cannot satisfactorily explain the delay of 7 years between
      the two events. Here we present the results of a three-dimensional viscoelastic
      model that simulates stress transfer from the ductile lower crust and upper
      mantle to the brittle upper crust in the 7 years following the Landers
      earthquake. Using viscoelastic parameters that can reproduce the observed
      horizontal surface deformation following the Landers earthquake, our calculations
      suggest that lower-crustal or upper-mantle flow can lead to postseismic stress
      increases of up to 1-2 bar at the location of the Hector Mine hypocentre during
      this time period, contributing to the eventual occurrence of the 1999 Hector Mine
      earthquake. These results attest to the importance of considering viscoelastic
      processes in the assessment of seismic hazard.

PMID- 11346792
TI  - Emperor penguins and climate change.
AB  - Variations in ocean-atmosphere coupling over time in the Southern Ocean have
      dominant effects on sea-ice extent and ecosystem structure, but the ultimate
      consequences of such environmental changes for large marine predators cannot be
      accurately predicted because of the absence of long-term data series on key
      demographic parameters. Here, we use the longest time series available on
      demographic parameters of an Antarctic large predator breeding on fast ice and
      relying on food resources from the Southern Ocean. We show that over the past 50
      years, the population of emperor penguins (Aptenodytes forsteri) in Terre Adelie
      has declined by 50% because of a decrease in adult survival during the late
      1970s. At this time there was a prolonged abnormally warm period with reduced sea
      ice extent. Mortality rates increased when warm sea-surface temperatures occurred
      in the foraging area and when annual sea-ice extent was reduced, and were higher
      for males than for females. In contrast with survival, emperor penguins hatched
      fewer eggs when winter sea-ice was extended. These results indicate strong and
      contrasting effects of large-scale oceanographic processes and sea-ice extent on
      the demography of emperor penguins, and their potential high susceptibility to
      climate change.

PMID- 11346794
TI  - Scalable architecture in mammalian brains.
AB  - Comparison of mammalian brain parts has often focused on differences in absolute
      size, revealing only a general tendency for all parts to grow together. Attempts
      to find size-independent effects using body weight as a reference variable
      obscure size relationships owing to independent variation of body size and give
      phylogenies of questionable significance. Here we use the brain itself as a size
      reference to define the cerebrotype, a species-by-species measure of brain
      composition. With this measure, across many mammalian taxa the cerebellum
      occupies a constant fraction of the total brain volume (0.13 +/- 0.02), arguing
      against the hypothesis that the cerebellum acts as a computational engine
      principally serving the neocortex. Mammalian taxa can be well separated by
      cerebrotype, thus allowing the use of quantitative neuroanatomical data to test
      evolutionary relationships. Primate cerebrotypes have progressively shifted and
      neocortical volume fractions have become successively larger in lemurs and
      lorises, New World monkeys, Old World monkeys, and hominoids, lending support to
      the idea that primate brain architecture has been driven by directed selection
      pressure. At the same time, absolute brain size can vary over 100-fold within a
      taxon, while maintaining a relatively uniform cerebrotype. Brains therefore
      constitute a scalable architecture.

PMID- 11346793
TI  - Host recognition by the tobacco hornworm is mediated by a host plant compound.
AB  - It is generally believed that animals make decisions about the selection of
      mates, kin or food on the basis of pre-constructed recognition templates. These
      templates can be innate or acquired through experience. An example of an acquired
      template is the feeding preference exhibited by larvae of the moth, Manduca
      sexta. Naive hatchlings will feed and grow successfully on many different plants
      or artificial diets, but once they have fed on a natural host they become
      specialist feeders. Here we show that the induced feeding preference of M. sexta
      involves the formation of a template to a steroidal glycoside, indioside D, that
      is present in solanaceous foliage. This compound is both necessary and sufficient
      to maintain the induced feeding preference. The induction of host plant
      specificity is at least partly due to a tuning of taste receptors to indioside D.
      The taste receptors of larvae fed on host plants show an enhanced response to
      indioside D as compared with other plant compounds tested.

PMID- 11346795
TI  - An evolutionary scaling law for the primate visual system and its basis in
      cortical function.
AB  - A hallmark of mammalian brain evolution is the disproportionate increase in
      neocortical size as compared with subcortical structures. Because primary visual
      cortex (V1) is the most thoroughly understood cortical region, the visual system
      provides an excellent model in which to investigate the evolutionary expansion of
      neocortex. I have compared the numbers of neurons in the visual thalamus (lateral
      geniculate nucleus; LGN) and area V1 across primate species. Here I find that the
      number of V1 neurons increases as the 3/2 power of the number of LGN neurons. As
      a consequence of this scaling law, the human, for example, uses four times as
      many V1 neurons per LGN neuron (356) to process visual information as does a
      tarsier (87). I argue that the 3/2 power relationship is a natural consequence of
      the organization of V1, together with the requirement that spatial resolution in
      V1 should parallel the maximum resolution provided by the LGN. The additional
      observation that thalamus/neocortex follows the same evolutionary scaling law as
      LGN/V1 may suggest that neocortex generally conforms to the same organizational
      principle as V1.

PMID- 11346796
TI  - Interocular rivalry revealed in the human cortical blind-spot representation.
AB  - To understand conscious vision, scientists must elucidate how the brain selects
      specific visual signals for awareness. When different monocular patterns are
      presented to the two eyes, they rival for conscious expression such that only one
      monocular image is perceived at a time. Controversy surrounds whether this
      binocular rivalry reflects neural competition among pattern representations or
      monocular channels. Here we show that rivalry arises from interocular
      competition, using functional magnetic resonance imaging of activity in a
      monocular region of primary visual cortex corresponding to the blind spot. This
      cortical region greatly prefers stimulation of the ipsilateral eye to that of the
      blind-spot eye. Subjects reported their dominant percept while viewing rivalrous
      orthogonal gratings in the visual location corresponding to the blind spot and
      its surround. As predicted by interocular rivalry, the monocular blind-spot
      representation was activated when the ipsilateral grating became perceptually
      dominant and suppressed when the blind-spot grating became dominant. These
      responses were as large as those observed during actual alternations between the
      gratings, indicating that rivalry may be fully resolved in monocular visual
      cortex. Our findings provide the first physiological evidence, to our knowledge,
      that interocular competition mediates binocular rivalry, and indicate that V1 may
      be important in the selection and expression of conscious visual information.

PMID- 11346797
TI  - Linkage disequilibrium in the human genome.
AB  - With the availability of a dense genome-wide map of single nucleotide
      polymorphisms (SNPs), a central issue in human genetics is whether it is now
      possible to use linkage disequilibrium (LD) to map genes that cause disease. LD
      refers to correlations among neighbouring alleles, reflecting 'haplotypes'
      descended from single, ancestral chromosomes. The size of LD blocks has been the
      subject of considerable debate. Computer simulations and empirical data have
      suggested that LD extends only a few kilobases (kb) around common SNPs, whereas
      other data have suggested that it can extend much further, in some cases greater
      than 100 kb. It has been difficult to obtain a systematic picture of LD because
      past studies have been based on only a few (1-3) loci and different populations.
      Here, we report a large-scale experiment using a uniform protocol to examine 19
      randomly selected genomic regions. LD in a United States population of north
      European descent typically extends 60 kb from common alleles, implying that LD
      mapping is likely to be practical in this population. By contrast, LD in a
      Nigerian population extends markedly less far. The results illuminate human
      history, suggesting that LD in northern Europeans is shaped by a marked
      demographic event about 27,000-53,000 years ago.

PMID- 11346798
TI  - The Ph1 locus is needed to ensure specific somatic and meiotic centromere
      association.
AB  - The correct pairing and segregation of chromosomes during meiosis is essential
      for genetic stability and subsequent fertility. This is more difficult to achieve
      in polyploid species, such as wheat, because they possess more than one diploid
      set of similar chromosomes. In wheat, the Ph1 locus ensures correct homologue
      pairing and recombination. Although clustering of telomeres into a bouquet early
      in meiosis has been suggested to facilitate homologue pairing, centromeres
      associate in pairs in polyploid cereals early during floral development. We can
      now extend this observation to root development. Here we show that the Ph1 locus
      acts both meiotically and somatically by reducing non-homologous centromere
      associations. This has the effect of promoting true homologous association when
      centromeres are induced to associate. In fact, non-homologously associated
      centromeres separate at the beginning of meiosis in the presence, but not the
      absence, of Ph1. This permits the correction of homologue association during the
      telomere-bouquet stage in meiosis. We conclude that the Ph1 locus is not
      responsible for the induction of centromere association, but rather for its
      specificity.

PMID- 11346799
TI  - Phagocytosis and clearance of apoptotic cells is mediated by MER.
AB  - Apoptosis is fundamental to the development and maintenance of animal tissues and
      the immune system. Rapid clearance of apoptotic cells by macrophages is important
      to inhibit inflammation and autoimmune responses against intracellular antigens.
      Here we report a new function for Mer, a member of the Axl/Mer/Tyro3 receptor
      tyrosine kinase family. mer(kd) mice with a cytoplasmic truncation of Mer had
      macrophages deficient in the clearance of apoptotic thymocytes. This was
      corrected in chimaeric mice reconstituted with bone marrow from wild-type
      animals. Primary macrophages isolated from mer(kd) mice showed that the
      phagocytic deficiency was restricted to apoptotic cells and was independent of Fc
      receptor-mediated phagocytosis or ingestion of other particles. The inability to
      clear apoptotic cells adequately may be linked to an increased number of nuclear
      autoantibodies in mer(kd) mice. Thus, the Mer receptor tyrosine kinase seems to
      be critical for the engulfment and efficient clearance of apoptotic cells. This
      has implications for inflammation and autoimmune diseases such as systemic lupus
      erythematosus.

PMID- 11346800
TI  - Mobilization of transposons by a mutation abolishing full DNA methylation in
      Arabidopsis.
AB  - A major component of the large genomes of higher plants and vertebrates comprises
      transposable elements and their derivatives, which potentially reduce the
      stability of the genome. It has been proposed that methylation of cytosine
      residues may suppress transposition, but experimental evidence for this has been
      limited. Reduced methylation of repeat sequences results from mutations in the
      Arabidopsis gene DDM1 (decrease in DNA methylation), which encodes a protein
      similar to the chromatin-remodelling factor SWI2/SNF2 (ref. 7). In the ddm1
      induced hypomethylation background, silent repeat sequences are often reactivated
      transcriptionally, but no transposition of endogenous elements has been observed.
      A striking feature of the ddm1 mutation is that it induces developmental
      abnormalities by causing heritable changes in other loci. Here we report that one
      of the ddm1-induced abnormalities is caused by insertion of CAC1, an endogenous
      CACTA family transposon. This class of Arabidopsis elements transposes and
      increases in copy number at high frequencies specifically in the ddm1
      hypomethylation background. Thus the DDM1 gene not only epigenetically ensures
      proper gene expression, but also stabilizes transposon behaviour, possibly
      through chromatin remodelling or DNA methylation.

PMID- 11346801
TI  - The structural basis of Arfaptin-mediated cross-talk between Rac and Arf
      signalling pathways.
AB  - Small G proteins are GTP-dependent molecular switches that regulate numerous
      cellular functions. They can be classified into homologous subfamilies that are
      broadly associated with specific biological processes. Cross-talk between small G
      protein families has an important role in signalling, but the mechanism by which
      it occurs is poorly understood. The coordinated action of Arf and Rho family
      GTPases is required to regulate many cellular processes including lipid
      signalling, cell motility and Golgi function. Arfaptin is a ubiquitously
      expressed protein implicated in mediating cross-talk between Rac (a member of the
      Rho family) and Arf small GTPases. Here we show that Arfaptin binds specifically
      to GTP-bound Arf1 and Arf6, but binds to Rac.GTP and Rac.GDP with similar
      affinities. The X-ray structure of Arfaptin reveals an elongated, crescent-shaped
      dimer of three-helix coiled-coils. Structures of Arfaptin with Rac bound to
      either GDP or the slowly hydrolysable analogue GMPPNP show that the switch
      regions adopt similar conformations in both complexes. Our data highlight
      fundamental differences between the molecular mechanisms of Rho and Ras family
      signalling, and suggest a model of Arfaptin-mediated synergy between the Arf and
      Rho family signalling pathways.

PMID- 11346805
TI  - Use of transesophageal echocardiography to guide cardioversion in patients with
      atrial fibrillation.
AB  - BACKGROUND: The conventional treatment strategy for patients with atrial
      fibrillation who are to undergo electrical cardioversion is to prescribe warfarin
      for anticoagulation for three weeks before cardioversion. It has been proposed
      that if transesophageal echocardiography reveals no atrial thrombus,
      cardioversion may be performed safely after only a short period of anticoagulant
      therapy. METHODS: In a multicenter, randomized, prospective clinical trial, we
      enrolled 1222 patients with atrial fibrillation of more than two days' duration
      and assigned them to either treatment guided by the findings on transesophageal
      echocardiography or conventional treatment. The composite primary end point was
      cerebrovascular accident, transient ischemic attack, and peripheral embolism
      within eight weeks. Secondary end points were functional status, successful
      restoration and maintenance of sinus rhythm, hemorrhage, and death. RESULTS:
      There was no significant difference between the two treatment groups in the rate
      of embolic events (five embolic events among 619 patients in the transesophageal
      echocardiography group [0.8 percent]) vs. three among 603 patients in the
      conventional-treatment group [0.5 percent], P=0.50). However, the rate of
      hemorrhagic events was significantly lower in the transesophageal
      echocardiography group (18 events [2.9 percent] vs. 33 events [5.5 percent],
      P=0.03). Patients in the transesophageal-echocardiography group also had a
      shorter time to cardioversion (mean [+/-SD], 3.0+/-5.6 vs. 30.6+/-10.6 days,
      P<0.001) and a greater rate of successful restoration of sinus rhythm (440
      patients [71.1 percent] vs. 393 patients [65.2 percent], P=0.03). At eight weeks,
      there were no significant differences between the two groups in the rates of
      death or maintenance of sinus rhythm or in functional status. CONCLUSIONS: The
      use of transesophageal echocardiography to guide the management of atrial
      fibrillation may be considered a clinically effective alternative strategy to
      conventional therapy for patients in whom elective cardioversion is planned.

PMID- 11346806
TI  - The effect of chelation therapy with succimer on neuropsychological development
      in children exposed to lead.
AB  - BACKGROUND: Thousands of children, especially poor children living in
      deteriorated urban housing, are exposed to enough lead to produce cognitive
      impairment. It is not known whether treatment to reduce blood lead levels
      prevents or reduces such impairment. METHODS: We enrolled 780 children with blood
      lead levels of 20 to 44 microg per deciliter (1.0 to 2.1 micromol per liter) in a
      randomized, placebo-controlled, double-blind trial of up to three 26-day courses
      of treatment with succimer, a lead chelator that is administered orally. The
      children lived in deteriorating inner-city housing and were 12 to 33 months of
      age at enrollment; 77 percent were black, and 5 percent were Hispanic. Follow-up
      included tests of cognitive, motor, behavioral, and neuropsychological function
      over a period of 36 months. RESULTS: During the first six months of the trial,
      the mean blood lead level in the children given succimer was 4.5 microg per
      deciliter (0.2 micromol per liter) lower than the mean level in the children
      given placebo (95 percent confidence interval, 3.7 to 5.3 microg per deciliter
      [0.2 to 0.3 micromol per liter]). At 36 months of follow-up, the mean IQ score of
      children given succimer was 1 point lower than that of children given placebo,
      and the behavior of children given succimer was slightly worse as rated by a
      parent. However, the children given succimer scored slightly better on the
      Developmental Neuropsychological Assessment, a battery of tests designed to
      measure neuropsychological deficits thought to interfere with learning. All these
      differences were small, and none were statistically significant. CONCLUSIONS:
      Treatment with succimer lowered blood lead levels but did not improve scores on
      tests of cognition, behavior, or neuropsychological function in children with
      blood lead levels below 45 microg per deciliter. Since succimer is as effective
      as any lead chelator currently available, chelation therapy is not indicated for
      children with these blood lead levels.

PMID- 11346807
TI  - Control of vancomycin-resistant enterococcus in health care facilities in a
      region.
AB  - BACKGROUND: In late 1996, vancomycin-resistant enterococci were first detected in
      the Siouxland region of Iowa, Nebraska, and South Dakota. A task force was
      created, and in 1997 the assistance of the Centers for Disease Control and
      Prevention was sought in assessing the prevalence of vancomycin-resistant
      enterococci in the region's facilities and implementing recommendations for
      screening, infection control, and education at all 32 health care facilities in
      the region. METHODS: The infection-control intervention was evaluated in October
      1998 and October 1999. We performed point-prevalence surveys, conducted a case
      control study of gastrointestinal colonization with vancomycin-resistant
      enterococci, and compared infection-control practices and screening policies for
      vancomycin-resistant enterococci at the acute care and long-term care facilities
      in the Siouxland region. RESULTS: Perianal-swab samples were obtained from 1954
      of 2196 eligible patients (89 percent) in 1998 and 1820 of 2049 eligible patients
      (89 percent) in 1999. The overall prevalence of vancomycin-resistant enterococci
      at 30 facilities that participated in all three years of the study decreased from
      2.2 percent in 1997 to 1.4 percent in 1998 and to 0.5 percent in 1999 (P<0.001 by
      chi-square test for trend). The number of facilities that had had at least one
      patient with vancomycin-resistant enterococci declined from 15 in 1997 to 10 in
      1998 to only 5 in 1999. At both acute care and long-term care facilities, the
      risk factors for colonization with vancomycin-resistant enterococci were prior
      hospitalization and treatment with antimicrobial agents. Most of the long-term
      care facilities screened for vancomycin-resistant enterococci (26 of 28 in 1998
      [93 percent] and 23 of 25 in 1999 [92 percent]) and had infection-control
      policies to prevent the transmission of vancomycin-resistant enterococci (22 of
      25 [88 percent] in 1999). All four acute care facilities had screening and
      infection-control policies for vancomycin-resistant enterococci in 1998 and 1999.
      CONCLUSIONS: An active infection-control intervention, which includes the
      obtaining of surveillance cultures and the isolation of infected patients, can
      reduce or eliminate the transmission of vancomycin-resistant enterococci in the
      health care facilities of a region.

PMID- 11346808
TI  - Effect of parathyroid hormone (1-34) on fractures and bone mineral density in
      postmenopausal women with osteoporosis.
AB  - BACKGROUND: Once-daily injections of parathyroid hormone or its amino-terminal
      fragments increase bone formation and bone mass without causing hypercalcemia,
      but their effects on fractures are unknown. METHODS: We randomly assigned 1637
      postmenopausal women with prior vertebral fractures to receive 20 or 40 microg of
      parathyroid hormone (1-34) or placebo, administered subcutaneously by the women
      daily. We obtained vertebral radiographs at base line and at the end of the study
      (median duration of observation, 21 months) and performed serial measurements of
      bone mass by dual-energy x-ray absorptiometry. RESULTS: New vertebral fractures
      occurred in 14 percent of the women in the placebo group and in 5 percent and 4
      percent, respectively, of the women in the 20-microg and 40-microg parathyroid
      hormone groups; the respective relative risks of fracture in the 20-microg and 40
      microg groups, as compared with the placebo group, were 0.35 and 0.31 (95 percent
      confidence intervals, 0.22 to 0.55 and 0.19 to 0.50). New nonvertebral fragility
      fractures occurred in 6 percent of the women in the placebo group and in 3
      percent of those in each parathyroid hormone group (relative risk, 0.47 and 0.46,
      respectively [95 percent confidence intervals, 0.25 to 0.88 and 0.25 to 0.861).
      As compared with placebo, the 20-microg and 40-microg doses of parathyroid
      hormone increased bone mineral density by 9 and 13 more percentage points in the
      lumbar spine and by 3 and 6 more percentage points in the femoral neck; the 40
      microg dose decreased bone mineral density at the shaft of the radius by 2 more
      percentage points. Both doses increased total-body bone mineral by 2 to 4 more
      percentage points than did placebo. Parathyroid hormone had only minor side
      effects (occasional nausea and headache). CONCLUSIONS: Treatment of
      postmenopausal osteoporosis with parathyroid hormone (1-34) decreases the risk of
      vertebral and nonvertebral fractures; increases vertebral, femoral, and total
      body bone mineral density; and is well tolerated. The 40-microg dose increased
      bone mineral density more than the 20-microg dose but had similar effects on the
      risk of fracture and was more likely to have side effects.

PMID- 11346809
TI  - Images in clinical medicine. Papilledema associated with intracranial
      hypertension.

PMID- 11346810
TI  - Racial differences in the use of cardiac catheterization after acute myocardial
      infarction.
AB  - BACKGROUND: Several studies have reported that black patients are less likely
      than white patients to undergo cardiac catheterization after acute myocardial
      infarction. The role of the race of the physician in this pattern is unknown.
      METHODS: We analyzed data from the Cooperative Cardiovascular Project, a study of
      Medicare beneficiaries hospitalized for acute myocardial infarction in 1994 and
      1995, to evaluate whether differences between black patients and white patients
      in the use of cardiac catheterization within 60 days after acute myocardial
      infarction varied according to the race of their attending physician. RESULTS:
      Our study cohort consisted of 35,676 white and 4039 black patients with acute
      myocardial infarction who were treated by 17,550 white and 588 black physicians.
      Black patients had lower rates of cardiac catheterization than white patients,
      regardless of whether their attending physician was white (rate of
      catheterization, 38.4 percent vs. 45.7 percent; P< 0.001) or black (38.2 percent
      vs. 49.6 percent, P<0.001). We did not find a significant interaction between the
      race of the patients and the race of the physicians in the use of cardiac
      catheterization. The adjusted mortality rate among black patients was lower than
      or similar to that among white patients for up to three years after the
      infarction. CONCLUSIONS: Racial differences in the use of cardiac catheterization
      are similar among patients treated by white physicians and those treated by black
      physicians, suggesting that this pattern of care is independent of the race of
      the physician.

PMID- 11346811
TI  - Spontaneous intracerebral hemorrhage.

PMID- 11346812
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 14-2001. A 47-year-old woman with diabetes, Crohn's colitis, and
      a painful swelling of the foot.

PMID- 11346813
TI  - Strategies for cardioversion of atrial fibrillation--time for a change?

PMID- 11346814
TI  - Primary prevention of childhood lead poisoning--the only solution.

PMID- 11346815
TI  - Racial disparities in medical care.

PMID- 11346816
TI  - Today's learning point.

PMID- 11346817
TI  - [Stereotaxic biopsy and 192Ir implant in intracranial tumors. A review of 7 years
      of experience].
AB  - INTRODUCTION: The combination of stereotaxic techniques, advances in neuroimaging
      and the creation of continually improving software has permitted stereotaxic
      biopsy of cerebral lesions at the most varied sites. Improvement in the method of
      permanent interstitial radiation (brachytherapy) improves the precision with
      which the radioactive sources may be inserted, releasing a maximum dose of
      radiation to the tumour with minimum radiation to the surrounding tissue.
      PATIENTS AND METHODS: We treated 237 patients (aged 1 to 78 years) with
      intracranial lesions, all included in the protocol of our centre. Stereotaxic
      systems of Leksell, Riechert-Mundinger, Micromar and Estereoflex were used. The
      procedure was in three stages: acquisition of the image, surgical planning and
      surgical operation. The imaging guide was the computerized axial tomography
      (CAT). RESULTS: Stereotaxic biopsy guided by CAT images was done in 153 patients.
      These were divided into three groups, taking the biopsy findings as the
      reference: group A (primary tumors, 128), group B (metastatic tumors, 15) and
      group C (non-malignant lesions, 10). Ninety six permanent implants of 192Ir were
      inserted, with a low dose of 4-7 cGy/h and a total dose of 80-120 Gy.
      CONCLUSIONS: Stereotaxic biopsy is a very effective procedure with a
      significantly low range of complications. The permanent implant with a low dose
      rate, well situated and using a source of 192Ir is a safe, simple, effective
      method for the treatment of primary and recurrent glial tumours, and non-glial
      tumours which fulfil criteria for this type of brachytherapy.

PMID- 11346818
TI  - [Course of drug-resistant childhood epilepsy treated with topiramate].
AB  - INTRODUCTION: The variable proportion of cases with childhood epilepsy resistant
      to treatment, has led to the development of different new drugs. OBJECTIVE: To
      study the efficacy of topiramate as add-on therapy in the everyday practice of a
      neuropaediatric clinic. PATIENTS AND METHODS: A retrospective study of all the
      patients treated with topiramate in a hospital outpatient clinic was performed.
      OUTCOME MEASUREMENT: 1. Reduction in >/= 50% as compared to basal frequency
      (partial control) and total control of seizures, and 2. Duration of drug
      treatment, using the Kaplan-Meier method. RESULTS: We studied 31 courses of
      treatment in 29 children. The aetiology of the epileptic syndromes was:
      idiopathic epilepsy (3.3%), cryptogenic epilepsy (58%) and symptomatic epilepsy
      (38.7%). We found a >/= 50% reduction in the basal monthly frequency of seizures
      after 3 months of treatment in 52% of the patients, which persisted 18 months
      later in 25%. Total control of seizures was obtained in 18.5% of the patients
      after 3 months of treatment, and this response was maintained 12 months later in
      12.5%. The probability of maintaining treatment with topiramate for 6 months was
      80%, and for 12 months was 49%. The average duration of treatment was 7.9 months
      (interval 1-29 months). Topiramate was suspended in 9 patients (29%). CONCLUSION:
      In difficult to treat childhood epilepsy topiramate as add-on therapy provides a
      partial and total responses which are similar to those reported with classical
      drugs, and depend on the duration of follow-up.

PMID- 11346819
TI  - [Acute disseminated encephalomyelitis in childhood. Report of 10 cases].
AB  - INTRODUCTION: Acute disseminated encephalomyelitis (ADEM) is a postinfectious
      encephalitis that is usually preceded by an infectious disease or vaccination.
      The clinical presentation has a wide spectrum and complementary exams are none
      specific, except magnetic resonance imaging (MRI) findings showing multifocal
      white-matter lesions similar to those seen en multiple sclerosis. PATIENTS AND
      METHODS: We report 10 children with the diagnosis of ADEM. We describe the
      clinical course and response to treatment. RESULTS: The prodroms were fever in
      all cases except one. The most common neurological symptoms were consciousness
      impairment, headache and seizures. The cerebrospinal fluid examination was
      abnormal in 9 patients with positive serologic test to enterovirus in one of
      them. MRI showed hyperintense multifocal subcortical white-matter lesions on T2
      mediated images. Treatment with steroids was given to 5 patients, steroids and
      immunoglobulins to one patient and symptomatic treatment to the rest. From the
      last group one patient relapsed and then received corticosteroid treatment. The
      follow up revealed a complete recovery in 6/7 patients that received steroids.
      Three patients have sequelae and of these, 2 received only symptomatic treatment.
      CONCLUSIONS: The diagnosis of ADEM is based on clinical and radiologic features,
      once other entities have been excluded. At the moment of suspicious of ADEM a
      brain-spinal chord MRI should be done, seeing that TAC brings not much
      information at the beginning. The treatment with steroids seems to be the most
      effective and the prognosis good, specially in cases that respond rapidly to it.

PMID- 11346820
TI  - [Extrarenal effects of furosemide on normal and ischemic cerebral tissue in the
      rat].
AB  - INTRODUCTION: Recent studies suggest that furosemide (FUR), a chloride
      cotransporting antagonist, acts directly on neurons of central nervous system
      modifying the ionic flow. OBJECTIVE: The aim of the present study was to
      determine the extrarenal antiedema effect of FUR. MATERIAL AND METHODS: Male
      Sprague-Dawley rats were anesthetized with tiobarbital (60 mg/kg-1 ip),
      bilaterally nephrectomized and perfunded iv with solution of Ringer (RIN) (n= 5)
      or FUR (40 mg/kg-1) (n= 6), in equivalent volumes. The diuretic effect of FUR was
      excluded by bilateral nephrectomy. Two tungsten microelectrodes implanted on the
      cerebral cortex, registered the tissue impedance by the voltage fall of a square
      wave electric pulse (100 mA, 10 ms) tested every 120 seconds, before and after
      infusion of FUR or RIN and during global cerebral ischemia by D-tubocurarine
      induced respiratory arrest. RESULTS: Preischemic FUR infusion induced a
      significant increase of voltage (t= 15.68; p< 0.0001). During global cerebral
      ischemia, the voltage fall was significantly lower in FUR than for RIN infusion
      (Wilcoxon Z= 3.9; p< 0.00001). CONCLUSION: These results suggest that FUR reduced
      significantly the cerebral impedance i.e. antiedema effect, by an extrarenal
      action, under both basal and ischemia conditions.

PMID- 11346821
TI  - [Stereotaxic microsurgical resection of intracranial tumors guided by imaging and
      assisted by computer].
AB  - INTRODUCTION: The microsurgical techniques for resection of intracranial lesions
      are limited where anatomical references do not exist or cannot be used as guides
      in the dissection of deeply located lesions or in more superficial eloquent
      areas. The stereotaxic guide, guided by imaging gives precise volumetric and
      geometric definition in intracranial lesions. Its application in the resection of
      intracranial tumors has special characteristics due to their biological condition
      and varied localization. OBJECTIVES: Spatial orientation during surgery is
      essential. We show this application of stereotaxic surgery in the Centro
      Internacional de Restauracion Neurologica (CIREN) in La Havana, Cuba, between May
      1994 and February 1988, describing 65 microsurgical operations done using
      stereotaxis in 62 patients with intracranial cerebral tumors. PATIENTS AND
      METHODS: The procedure was divided into three stages: acquiring an image,
      computerized axial tomography and surgical planning, with the STASSIS planning
      system and microsurgical procedures, including systems of stereotaxis: Leksell,
      Micromar and Estereoflex. RESULTS: Of the total, 27 of these patients had glial
      tumors, 33 non-glial tumors and only 2 had non-neoplastic lesions of different
      sites and sizes. A total of 30 resections were done. Surgical morbidity was
      minimal and there was no surgical mortality. CONCLUSIONS: The main advantages of
      this method are: exact localization of the site for craniotomy, easy spatial
      orientation and ease in distinguishing the delimitation between the tumour and
      the healthy tissue. It has been shown that Estereoflex may be used in cerebral
      microsurgery.

PMID- 11346822
TI  - [The importance of multifactorial rehabilitation treatment in amyotrophic lateral
      sclerosis].
AB  - INTRODUCTION: The treatment of amyotrophic lateral sclerosis (ALS) is still a
      major challenge. Rehabilitation treatment is scarcely considered and its
      usefulness in these patients continues to be controversial. PATIENTS AND METHODS:
      A multidisciplinary team made up of neurologists, physiotherapists, logopaedists,
      defectologists, psychologists and specialist physicians treated six patients with
      ALS in an intensive rehabilitation programme of 41 hours per week for four weeks.
      We follow certain basic principles in rehabilitation including: 1. Treatment by a
      multidisclipinary team; 2. Treatment tailored to the individual; 3. Avoidance of
      muscle fatigue and vigorous exercise, and 4. Intensive treatment with carefully
      measured amounts of different activities (logophoniatrics, occupational therapy,
      psychology, physical therapy, etc.) to avoid fatigue. The patients fulfilled the
      criteria of E1 Escorial for the diagnosis of definite ALS, and gave their
      informed consent to undergo the treatment. Forced Vital Capacity (FVC) and ALS
      Functional Rating Scale (ALSFRS) tests were done on all patients at the beginning
      and end of the treatment. The Wilcoxon test for paired series, comparing scores
      at the start and finish, were done in each case. RESULTS: In all patients the FVC
      and ALSFRS improved after the treatment. The results were statistically
      significant (Z: 2.2013; p= 0.027) on the Wilcoxon paired series test and no
      complications were seen. CONCLUSIONS: Intensive, multifactorial rehabilitation
      treatment for four weeks improved the FVC and ALSFRS in all patients with ALS and
      no complications were seen. Until there is a curative treatment for ALS,
      multifactorial rehabilitation remains the best hope for these patients.

PMID- 11346823
TI  - [Multifocal motor neuropathy with partial block of nerve conduction].
AB  - INTRODUCTION: Multifocal motor neuropathy with partial conduction block is
      characterized by being a chronic, demyelinating, autoimmune severely disabling
      neuropathy. In Cuba three cases were reported by Dr. Estrada et al in 1999. This
      neuropathy presents clinically in relatively young persons. The arms are
      predominantly affected and the typical signs are of severe asymmetrical weakness,
      with atrophy which is less marked than the weakness, fasciculations, cramps and
      myokymiae of the affected muscle. Neurophysiological study shows partial block of
      motor nerve conduction. Clinical interest is due to it being potentially curable.
      Many cases are wrongly diagnosed as motor neurone disease. CLINICAL CASES: We
      present five patients aged under 55 years with progressive chronic motor
      neuropathy mainly affecting their arms. Study of nerve conduction showed partial
      block of the conduction in motor nerves, in segments with no block of sensory
      neuroconduction. One patient had been diagnosed as having motor neurone disease;
      another had slight sensory involvement in the distal territory of the radial
      nerve; in two patients the symptoms affected all four limbs. In three patients
      good results were obtained with intacglobin, followed by azothroprine and
      prednisone. Two patients showed no improvement with this treatment so intravenous
      cyclophosphamide was given for nine months which stopped progression of the
      disorder. CONCLUSIONS: Multifocal motor neuropathy is potentially treatable. In
      some cases intacglobin azathioprine and prednisone may be a useful alternative to
      cyclophosphamide.

PMID- 11346824
TI  - [Preocclusive stenosis of the extracranial vertebral artery. Treatment by
      percutaneous transluminal angioplasty and insertion of endoprosthesis].
AB  - INTRODUCTION: Atherosclerotic occlusive disease of the extracranial portion of
      the vertebral artery is relatively frequent and is usually related to
      vertebrobasilar ischemia. Due to the lack of a noninvasive diagnostic technique,
      at present it is often not diagnosed. Surgical treatment is difficult and risky.
      Percutaneous transluminal angioplasty (PTA) is only partly useful due to a high
      rate of restenosis. The recent development of stenting has led to an evident
      improvement of PTA results, reducing restenosis and offering an effective
      treatment with low morbidity and mortality. CLINICAL CASE: Sixty year old male
      patient, smoker and moderate drinker, who is hospitalized due to repeated
      ischemic strokes (cerebellar stroke in the left posterior and interior inferior
      cerebellar arteries, and cerebral stroke at occipito-parietal and ipsilateral
      capsulo-thalamic levels) in spite of antithrombotic treatment. Angiography
      showed: a) occlusion of the left vertebral artery; b) preocclusive stenosis of
      the right vertebral artery in the ostium; c) fetal origin of the right posterior
      cerebral artery, and d) left hypoplasic posterior communicating artery. PTA and
      stent placement at the right vertebral artery is performed with an excellent
      angiographic result, a partial recovery of neurological symptomatology and
      absence of new episodes of cerebral ischemia during a three-month follow-up.
      CONCLUSION: Percutaneous transluminal angioplasty and stent placement is an
      effective low morbidity-mortality treatment in occlusive atherosclerosis of the
      vertebral artery, although further randomized multicenter studies are required in
      order to validate this conclusion.

PMID- 11346825
TI  - [Progressive amyotrophy of a limb as the presenting symptom of anchored spinal
      cord syndrome with spinal lipoma].
AB  - OBJECTIVE: We present a case of progressive amyotrophy of a limb as the
      presenting symptom of the anchored spinal cord syndrome and review the principal
      clinical features of the syndrome, diagnostic tests which are useful in
      differentiating it from other conditions and its treatment. CLINICAL CASE: We
      describe a case of a young woman in whom the spinal cord was anchored by a spinal
      lipoma. At the onset of the disorder she complained of progressive muscular
      atrophy of the right leg and difficulty in dorsi-flexion of her right foot. Plain
      X-ray of the pelvis showed partial agenesis of the right lower hemisacrum and
      partial sacralization of L5. Lumbosacral CT and MR showed a lipoma to be present
      within the spinal canal and the thickened filum terminale anchored within the
      lipoma. During the next five months after diagnosis, the clinical picture
      worsened with paresia of flexo-extension of the right knee and of flexion of the
      right foot. Surgical treatment was therefore indicated. CONCLUSIONS: The anchored
      spinal cord syndrome should be considered in the differential diagnosis of spinal
      cord disorders presenting in adults, when there are other malformations such as
      agenesis of the sacrum. Surgical treatment is always indicated when there is
      evidence of worsening clinical condition.

PMID- 11346827
TI  - [Idiopathic epileptic syndromes of the newborn].
AB  - INTRODUCTION: Seizures during the neonatal period are the characteristic clinical
      expression of dysfunction of the nervous system. Not all the seizures seen during
      the neonatal period are due to epilepsy which only occurs in 10%. DEVELOPMENT:
      The aetiology of neonatal seizures is very varied and is mainly due to different
      types of aggression to the brain during this early stage of life. Epileptic
      syndromes are very rare during the neonatal period. In general the prognosis is
      very bad as occurs in infantile epileptic encephalopathy of early onset or
      myoclonic encephalopathy of early onset. However, the International League
      Against Epilepsy (ILAE) has identified and recognized some idiopathic epileptic
      syndromes of the neonatal period with a somewhat better prognosis. Two major
      groups have been established including the benign neonatal epilepsies (benign
      idiopathic neonatal epilepsies and benign familial neonatal seizures) and the
      group of status epilepticus (severe idiopathic status epilepticus). CONCLUSION:
      We analyze the different types of epilepsy of the newborn, form of onset, current
      knowledge of molecular biology, treatment and prognosis.

PMID- 11346826
TI  - [Opsoclonic-myoclonic-ataxic syndrome].
AB  - INTRODUCTION: The opsoclonic-myoclonic-ataxic syndrome (OMAS) is that in which
      there are at least two of the cardinal signs (opsoclonus, myoclonus and ataxia).
      OBJECTIVES: To report three cases, their evolution and aetiology, and discuss the
      main physiopathological basis and guidelines for treatment. CLINICAL CASES: We
      present three cases admitted to the Internal Medicine Department with the
      diagnosis of OMAS. The investigations included standard biochemical and
      haematological tests, a full study of the cerebrospinal fluid, computerized axial
      tomography of the skull and thorax, and magnetic resonance. We describe the
      clinical presentation, evolution, aetiology and treatment given. The results of
      the complementary tests are shown in the form of tables. Finally we consider the
      diagnosis of this condition. Three patients, two men and one woman, aged between
      43 and 78 were diagnosed as having OMAS. The causes were: paraneoplasia, acute
      diffuse encephalomyelitis and probable multiple sclerosis. The patient with lung
      cancer died whilst the other two showed almost complete recovery on the treatment
      given. CONCLUSIONS: Our cases show that OMAS may be a feature of a diffuse
      process affecting the brainstem and cerebellum. The commonest causes found are
      multiple sclerosis, acute diffuse encephalomyelitis and as a paraneoplastic
      feature of a tumour. It may improve with treatment, but depending on the
      aetiology, death may occur. Immunomodulation treatment is vital even though
      symptomatic treatment may be given.

PMID- 11346828
TI  - [Classification of the aphasic syndrome].
AB  - INTRODUCTION: The clinical examination of language should form part of the
      general examination of the mental state in patients with diffuse cognitive
      disorders, intellectual disorders, disorders of memory, etc. OBJECTIVE: To focus
      the examination of language towards understanding and classification of
      linguistic activity, through study of aphasia. DEVELOPMENT: We analyze the
      semiological diversity of aphasia and most relevant clinical forms using a
      diagnostic decision tree to consider the clinical, neuropsychological and
      neuroanatomical characteristics. The more detailed the study of the aphasic
      disorder, the more difficult it is to fit the case into a particular clinical
      type. In fact, as may be seen from current publications, there are more and more
      studies of aphasic persons considered to have unclassifiable aphasia. The more
      and more detailed studies of neuropsychological disorders mean that we now find
      terms such as primary progressive aphasia, semantic dementia and anarthria or
      progressive aphemia. This groups of abnormal linguistic features appearing in
      patients with focal degenerative illness may lead to some confusion, not only in
      the clinicosemiological sphere but also with regard to diagnosis, classification
      and evolution of the disorder. CONCLUSIONS: By studying aphasia we may study the
      anatomofunctional basis of language more fully, investigate the different systems
      for processing information, study cases with particular dysfunctions and
      specifically evaluate, case by case, the numerous, complex components of
      linguistic activity.

PMID- 11346829
TI  - [Neuropsychological deficits in hydrocephalus associated spina bifida].
AB  - INTRODUCTION. The term spina bifida is used to describe a large number of
      abnormalities in which the common denominator is incomplete posterior fusion of
      the vertebral arches. DEVELOPMENT. Spina bifida, as a congenital alteration
      affecting closure of the neural tube frequently appears in relation to
      hydrocephaly. The object of this article is to review the neuropsychological
      alterations which occur in hydrocephaly, with special reference to hydrocephaly
      linked to spina bifida. The authors suggest consideration of these alterations in
      view of the new models of cognitive neuropsychology. The commonest alterations
      are those affecting visual-perceptive and visual-constructive function, working
      memory, pragmatic use of language and executive functions.

PMID- 11346830
TI  - A comparison of substance abuse and violence in the prediction of long-term
      rehabilitation outcomes after traumatic brain injury.
AB  - OBJECTIVE: To determine the relative contributions of substance abuse history and
      violent etiology to the prediction of outcomes for individuals who sustained a
      traumatic brain injury (TBI) requiring inpatient rehabilitation. DESIGN:
      Longitudinal study of outcomes 1 year postdischarge from rehabilitation. SETTING:
      Specialized TBI acute rehabilitation unit. PARTICIPANTS: Three hundred fifty-one
      individuals consecutively admitted for rehabilitation. INTERVENTIONS: Gathered
      data from patients' medical records (including etiology of injury, initial
      Glasgow Coma Scale scores, and FIMtrade mark instrument scores at discharge),
      demographic details, and history of substance abuse; phone and mail survey data
      from individuals (Satisfaction with Life Scale [SWLS]; Community Integration
      Questionnaire [CIQ]). MAIN OUTCOME MEASURES: CIQ and SWLS; relative contributions
      of injury etiology, demographic and injury-related dependent variables, and
      substance abuse history to predictive model. RESULTS: Almost 80% of persons with
      injuries from violence-related causes had a history of substance abuse. Substance
      abuse was found to contribute to the prediction of life satisfacton and
      productivity, while violent etiology was not a significant contributor to
      predictive models. CONCLUSION: Substance abuse history proved to be a strong
      predictor of long-term outcomes, while violent etiology of injury was less
      influential. The results of this study emphasize the need to include substance
      abuse history in all studies of outcomes after TBI, and to increase prevention
      efforts to limit the effects of such a history.

PMID- 11346831
TI  - Chronic lateral epicondylitis of the elbow: A prospective study of low-energy
      shockwave therapy and low-energy shockwave therapy plus manual therapy of the
      cervical spine.
AB  - OBJECTIVE: To compare the effects of extracorporeal shockwave therapy (ESWT)
      alone with a combination of ESWT and manual therapy of the cervical spine in
      treating chronic tennis elbow. DESIGN: Prospective, matched single-blind control
      trial. SETTING: University hospital clinic. PATIENTS: Thirty patients with
      unilateral chronic tennis elbow, an unsuccessful conservative therapy during the
      6 months before referral, and clinical signs of cervical dysfunction (eg,
      pressure pain at the C4-5 and/or C5-6 level, protraction of the head).
      INTERVENTIONS: Three times at weekly intervals all patients received 1000
      shockwave impulses of an energy flux density of.16mJ/mm(2) at the lateral elbow.
      Additionally, they underwent manual therapy of the cervical spine and the
      cervicothoracic junction 10 times (group I). For each patient, a control matched
      by age (3-yr range) and gender at first conservative treatment was drawn at
      random from 127 patients who had undergone low-energy shockwave therapy in the
      same unit in the past 3 years (group II). Follow-up examinations took place at 12
      weeks and at 12 months. MAIN OUTCOME MEASURES: The Roles and Maudsley outcome
      score at 12 months, defining an excellent or good result with no or only
      occasional discomfort without limitation of activity and range of motion.
      RESULTS: Neither group differed statistically before the study, with a poor
      rating for all patients (p >.05). At 12 months, there was still no significant
      difference, with the outcome being excellent or good in 56% in group I, and in
      60% in group II (p >.05). Each group showed significant improvement compared with
      the respective prestudy evaluation (p <.0001). CONCLUSION: ESWT may be an
      effective conservative treatment method for unilateral chronic tennis elbow. The
      efficacy of additional cervical manual therapy for lateral epicondylitis remains
      questionable.

PMID- 11346832
TI  - Bone growth increases the knee flexion contracture angle: A study using rats.
AB  - OBJECTIVES: To assess the impact of bone growth on the flexion contracture angle
      at the knee, to measure the bone growth pattern in rats, and to assess the impact
      of immobility on bone growth. DESIGN: Experimental, controlled study. SETTING:
      Bone and joint laboratory. ANIMALS: Sixty Sprague-Dawley rats. INTERVENTIONS:
      Knee joints of 40 rats were immobilized unilaterally in flexion. Sham-operated
      animals (n = 20) were controls. MAIN OUTCOME MEASURES: The contracture angle and
      the femur and tibia lengths on radiographs. RESULTS: The angle of flexion
      increased over time and was largely explained by bone growth (r =.725, p <.01).
      Femur and tibia grew in rats until they were 11 months old. Immobility enhanced
      growth in bone length, especially of the femur, after 16 and 32 weeks of
      immobility (p <.05). CONCLUSIONS: Knee flexion contracture angle increased as a
      consequence of normal bone growth, a situation that is also encountered in
      skeletally immature children. The continued growth in length of bones in children
      may influence the progression of contractures and add to the therapeutic
      challenge. Ongoing bone growth should be considered when interpreting reports
      that use animal models for bone and joint diseases.

PMID- 11346833
TI  - Spinal cord injury in Italy: A multicenter retrospective study.
AB  - OBJECTIVE: To investigate certain factors influencing the length of stay (LOS) in
      a rehabilitation center, the incidence of pressure ulcers, and the neurologic
      improvement of patients with traumatic (T/SCI) and nontraumatic spinal cord
      injury (NT/SCI). DESIGN: A multicenter retrospective study of patients with SCI
      admitted to rehabilitation centers between 1 January 1989 and 31 December 1994
      (only first admissions). SETTING: Seven Italian rehabilitation centers. PATIENTS:
      A total of 859 consecutively admitted adult patients with SCI. INTERVENTION:
      Examined medical records of patients admitted to rehabilitation centers. MAIN
      OUTCOME MEASURES: Pressure ulcers on admission as an indicator of nursing care in
      acute phase, LOS in rehabilitation centers, and neurologic improvement on
      discharge (using the Frankel classification system). Other measures included
      level of lesion, associated lesions (if T/SCI), surgical stabilization (if
      T/SCI), and time from the event to admission to a rehabilitation center. RESULTS:
      In all cases, the time from event to admission to a rehabilitation center
      exceeded 30 days (average +/- standard deviation: T/SCI, 54.6 +/- 43.7d; NT/SCI,
      166.9 +/- 574d); pressure ulcers on admission were present in 34.1% of T/SCI and
      17.1% of NT/SCI patients. The average LOS in a rehabilitation center was 143.1 +/
      89.1 days for T/SCI and 91.7 +/- 78.9 days for NT/SCI; Frankel grades improved
      by 1 or more in 34.4% of T/SCI and 34.1% of NT/SCI patients. The presence of
      pressure ulcers on admission, rehabilitation LOS, and neurologic improvement on
      discharge correlated highly with severe neurologic damage on admission in both
      T/SCI and NT/SCI patients as well as with management of the patient immediately
      before admission to a rehabilitation center, mainly in NT/SCI patients.
      CONCLUSIONS: Severe neurologic damage is the major determining factor in
      predicting neurologic recovery. Pressure ulcer prevention is statistically
      associated with neurologic improvement and the shortening of rehabilitation LOS.
      Patient management immediately before admission to rehabilitation has a
      statistical correlation with neurologic improvement in all patients studied and
      on both rehabilitation LOS and incidence of pressure ulcers in the NT/SCI
      patients.

PMID- 11346834
TI  - Validation test for climate control on air-loss supports.
AB  - OBJECTIVE: To develop a simple, reproducible validation test protocol for
      classification of air-loss support systems. DESIGN: Simultaneous experimental
      measurement of moisture loss and temperature reduction at the air-loss support
      surface-human body equivalent interface from a sweating human skin analogue.
      SETTING: A hospital department of physical medicine and rehabilitation. OTHER
      PARTICIPANTS: These 3 manufacturers contributed 14 support surfaces.
      INTERVENTIONS: Test support surfaces and a standard foam mattress were placed on
      a hospital bed. Water was circulated to a loading gauge, placed on a dry moisture
      reservoir, and connected to a water bath to keep the interface at 37 degrees +/-
      0.5 degrees C. The loading gauge and support surface was adjusted 23cm below the
      water bath level and the air flow through the interface initiated. After the dry
      moisture reservoir came to temperature equilibrium for 30 minutes, it was
      replaced with a wet one that was saturated with 36g of saline. The temperature
      change and evaporation rate were recorded throughout a 90-minute test period.
      MAIN OUTCOME MEASURES: Temperature of support surface interface and evaporation
      rate. RESULTS: Clustered data from temperature reduction and standardized rate of
      moisture loss yielded 3 groups of support surfaces in categories of no air loss
      (control), low air loss (LAL), and high air loss. The mean values of the
      characteristic temperature reduction and rate of moisture loss differed
      significantly between the groups. By multiple comparisons with Bonferroni's
      adjustment, the group means differed significantly for average temperature
      reduction (p <.017) and for standardized rate of moisture loss (p =.0001). The
      measured temperature change at any instant of time reflected the effect of
      evaporation and the opposing effect of thermal conductivity. CONCLUSION:
      Measurements of support interface climate change allowed for selective grouping
      of LAL surfaces according to rate of moisture evaporation and the resulting
      temperature reduction. Neither temperature change nor evaporation rate alone was
      sufficient to determine the microclimate characteristics of the support surface.
      Combined, these characteristics can effectively describe the performance of any
      LAL support system and may be used to define standards of performance.

PMID- 11346835
TI  - Electrodiagnostic changes of the lower limbs in subjects with chronic complete
      cervical spinal cord injury.
AB  - OBJECTIVE: To assess the electrodiagnostic changes in the lower limbs as measured
      by nerve conduction studies (NCSs) and electromyography in individuals with
      chronic complete tetraplegia. DESIGN: Prospective testing of NCS and
      electromyography. SETTING: Model spinal cord injury rehabilitation center.
      PARTICIPANTS: Twenty-five individuals with chronic complete tetraplegia without
      risk factors for peripheral neuropathy or other lower motoneuron disorders.
      INTERVENTIONS: Nerve conduction parameters recorded from the peroneal, tibial,
      and sural nerves, and compared with normal values. The presence of spontaneous
      activity (SA), including fibrillation and positive sharp waves, recorded in 5
      muscle groups-2 proximal (vastus medialis, iliopsoas), 2 distal (tibialis
      anterior, medial gastrocnemius), and L4 lumbar paraspinals. Analysis to see if
      the presence of SA correlated with the distance of the muscle from the spinal
      cord or with spasticity (measured by the modified Ashworth scale). MAIN OUTCOME
      MEASURES: Nerve conduction latencies and velocities; motor and sensory conduction
      latencies; compound muscle action potential (CMAP) and sensory nerve action
      potential amplitudes; spontaneous potentials: fibrillation and positive sharp
      waves; and spasticity. RESULTS: NCS responses were obtained at a decreased
      frequency relative to able-bodied subjects. Statistically significant results in
      comparison to normal means included a diminished sural amplitude, and diminished
      peroneal and tibial CMAP and nerve conduction velocity (p <.0001). SA was
      recorded in at least 1 of the muscles tested in 92% of subjects, with 72% having
      SA in more than 1 of the muscles tested affected. A significant difference was
      seen for SA in the medial gastrocnemius as compared with the iliopsoas (p =.039).
      No correlation was noted in terms of SA with degree of spasticity. CONCLUSION: A
      statistically significant difference in NCS responses in the lower limbs in
      chronic tetraplegia was found relative to normal control values. However, only
      the frequency of responses elicited and the decreased CMAP of the peroneal nerve
      are clinically significant. SA was present in many of the lower extremity muscles
      in the subjects. Predominantly axonal changes were evident in individuals with
      chronic complete tetraplegia.

PMID- 11346836
TI  - Coordination exercise and postural stability in elderly people: Effect of Tai Chi
      Chuan.
AB  - OBJECTIVE: To evaluate the effects of coordination exercise on postural stability
      in older individuals by Chinese shadow boxing, Tai Chi Chuan (TCC). DESIGN: Cross
      sectional study. SETTING: Research project in a hospital-based biomechanical
      laboratory. PARTICIPANTS: The TCC group (n = 25) had been practicing TCC
      regularly for 2 to 35 years. The control group (n = 14) included healthy and
      active older subjects. INTERVENTION: Static postural stability test:
      progressively harder sequential tests with 6 combinations of vision (eyes open,
      eyes closed, sway-referenced) and support (fixed, sway-referenced); and dynamic
      balance test: 3 tests of weight shifting (left to right, forward-backward,
      multidirectional) at 3 speeds. MAIN OUTCOME MEASURES: Static and dynamic balance
      of Sensory Organization Testing (SOT) of the Smart Balance Master System.
      RESULTS: In static postural control, the results showed no differences between
      the TCC or control group in the more simple conditions, but in the more
      complicated SOT (eyes closed with sway surface, sway vision with sway surface),
      the TCC group had significantly better results than the control group. The TCC
      group also had significantly better results in the rhythmic forward-backward
      weight-shifting test. Duration of practice did not seem to affect the stability
      of elder people. CONCLUSION: The elderly people who regularly practiced TCC
      showed better postural stability in the more challenged conditions than those who
      do not (eg, the condition with simultaneous disturbance of vision and
      proprioception). TCC as a coordination exercise may reduce the risk of a fall
      through maintaining the ability of posture control.

PMID- 11346837
TI  - The self-reported functional measure: Predictive validity for health care
      utilization in multiple sclerosis and spinal cord injury.
AB  - OBJECTIVE: To examine the predictive validity of the Self-Reported Functional
      Measure (SRFM), a new measure derived from the FIMtrade mark instrument, for
      health care utilization in multiple sclerosis (MS) and spinal cord injury (SCI).
      DESIGN: Prospective cohort study using a mailed survey in 1995 and administrative
      records from 1996 and 1997. SETTING: Veterans Health Administration hospitals and
      outpatient clinics. PATIENTS: A total of 6361 veterans with SCI and 1789 veterans
      with MS. MAIN OUTCOME MEASURES: SRFM score was compared with subsequent
      outpatient visits, hospitalizations, hospital lengths of stay (LOSs), and
      residence peri-hospitalization. Odds ratios (ORs) and 95% confidence intervals
      (CIs) were calculated for these variables. RESULTS: A total of 3836 subjects
      (47.6%) were hospitalized during 1996-1997, and all but 874 (10.7%) had 1 or more
      outpatient visits. SRFM score predicted inpatient, but not outpatient health care
      utilization. Persons in the lowest SRFM quartile were over 90% (OR = 1.91, 95% CI
      = 1.71-2.13) more likely to be hospitalized compared with those in the highest
      SRFM quartile; also, they were over 2 times (OR = 2.18, 95% CI = 1.85-2.57) more
      likely to have a LOS greater than 7 days, were over 2 times (OR = 2.41, 95% CI =
      1.62-3.58) more likely to die in hospital, and were nearly 3 times (OR = 2.86,
      95% CI = 2.00-4.08) more likely to be discharged to an institution. CONCLUSIONS:
      SRFM had excellent predictive validity for hospitalization, LOS, and discharge
      destination among patients with MS or SCI.

PMID- 11346838
TI  - The influence of stimulus cue on the initiation of stepping in young and older
      adults.
AB  - OBJECTIVES: To investigate the influence of different reaction stimulus cues on
      the characteristics of ground reaction forces during the initiation of rapid
      forward stepping, and to determine whether age-related differences in step
      initiation are influenced by the type of stimulus cue used to trigger stepping.
      DESIGN: Case-control study. SETTING: University-based research laboratory.
      PARTICIPANTS: Fifteen healthy younger adults and 35 community-dwelling older
      adult volunteers. MAIN OUTCOME MEASURES: Subjects performed forward step
      initiation in response to 3 different reaction stimulus cues (light, sound,
      electrocutaneous) during simple reaction-time conditions. Ground reaction force
      data were collected and used to characterize the timing and magnitude features of
      the postural (weight-transfer) and step components. RESULTS: In comparison with
      the light and sound stimuli, the nonnoxious electrocutaneous trigger cue was
      associated with an increase in the magnitude of the initial displacement of the
      center of pressure (COP) in the mediolateral direction. Overall, older subjects
      were slower to initiate the postural and step components, and displayed a
      reduction in the initial posterior displacement of the COP. CONCLUSIONS: The
      postural component for lateral weight transfer was augmented by the
      electrocutaneous trigger cue, suggesting its potential to enhance step initiation
      among clinical populations. Age-related changes in stepping were unaffected by
      the type of stimulus cue, but the older group had a slower response initiation
      time and less forward propulsion. The abilities of many older persons may be
      compromised in situations where rapid adjustments in the base of support through
      stepping are triggered by environmental stimuli.

PMID- 11346839
TI  - A multifactorial study of age bias among rehabilitation professionals.
AB  - OBJECTIVES: To assess different dimensions of age bias among rehabilitation
      professionals and to determine the effect of patient gender and behavior on these
      biases. DESIGN: Between-subjects questionnaire study. SETTING: Randomly selected
      institutions accredited with the Commission on the Accreditation of
      Rehabilitation Facilities (CARF). PARTICIPANTS: Nine hundred seventy-four
      rehabilitation professionals from 9 disciplines at 23 CARF-accredited facilities.
      INTERVENTIONS: Each professional received a vignette case history of an
      amputation patient who varied in age (36yr, 76yr), gender (male, female), and
      patient behavior (ideal, depressed, noncompliant). The vignette was followed by
      the Professional Bias Questionnaire (PBQ), which included 25 questions assessing
      the professionals' responses to the patient. MAIN OUTCOME MEASURES: Main effects
      and interaction effects for age, gender, and behavior for the PBQ. RESULTS:
      Factor analysis of the PBQ questionnaire yielded 4 reliable scales: the
      professional's judgment of the patient's psychologic neediness, postdischarge
      potential, worthiness for rehabilitation, and their personal reaction to working
      with the patient. Analyses of variance resulted in significant age by behavior
      interaction effects for 3 of the 4 scales. Older patients were viewed more
      negatively than equivalent younger patients when they were noncompliant.
      Professionals also had a more negative personal reaction to depressed older
      patients compared with equivalent younger patients. In contrast, gender bias was
      only found in 1 specific situation and did not interact with age bias.
      CONCLUSION: Several forms of bias toward older adult patients were found among
      rehabilitation professionals, but they were present only when patient behavior
      was less than ideal. Age bias continues to be a critical issue in the equity of
      rehabilitation services and should be addressed with training and policy changes.

PMID- 11346840
TI  - A simple institutional educational intervention to decrease use of selected
      expensive medications.
AB  - OBJECTIVE: To determine whether a simple educational intervention can influence
      use of prescription medications at an institution. DESIGN: Cost-effectiveness
      analysis of prescribing behavior before and after an educational intervention.
      SETTING: A large, urban, free-standing academic rehabilitation hospital.
      PARTICIPANTS: Physicians, residents, and physician extenders. INTERVENTIONS: The
      hospital's pharmacy department provided simple written educational material about
      cost differences of various prescription medications to attending and resident
      physicians, nurse leaders, and case managers. Telephoned reminders were given
      when targeted medications were prescribed. MAIN OUTCOME MEASURES: Total
      prescription medication use was recorded monthly for 12 months before and after
      the intervention. Pharmaceuticals monitored were subcutaneously administered
      anticoagulants, histamine type 2 (H2) blockers, and nonsteroidal anti
      inflammatory drugs (NSAIDs). RESULTS: A 32% decrease in use of the more costly
      anticoagulant and a 20% increase in use of the less costly anticoagulant (p
      <.0001), representing an estimated annual savings of nearly $66,000. Use of more
      costly H2 antagonist decreased 50% and use of less costly H2 antagonist increased
      128% (p <.0001). With written intervention only, use of more costly NSAIDs
      declined 28%, whereas use of less costly NSAIDs increased 58% (p <.0020).
      CONCLUSION: Providing physicians with simple pharmaceutical cost information and
      telephone reminders decreased the use of targeted more costly medications.

PMID- 11346841
TI  - Cerebral palsy in adults: Independent effects of muscle strength and muscle tone.
AB  - OBJECTIVE: To investigate clinical characteristics and their contribution to
      activities of daily living (ADLs) in adults with cerebral palsy (CP). DESIGN:
      Descriptions of the clinical features of medical disorders; survey. SETTING:
      Rehabilitation counseling center in Japan. PATIENTS: A case series of 256
      patients (140 men, 116 women; mean age, 31.6yr; range, 17-83yr) admitted to a
      rehabilitation center from January 1995 to December 1997. MAIN OUTCOME MEASURES:
      Characteristics investigated included severity of mental retardation, topography
      of motor deficits, motor power by manual muscle testing, muscle tone rated by
      using the muscle tone scale, deformity, sensory disturbance, and pain. ADLs were
      evaluated with the Barthel Index. RESULTS: Patients showed severe impairment in
      terms of the Ashworth scale for grading spasticity and deformity, and moderate
      impairment on manual muscle testing. ADLs were influenced significantly by
      topography of motor deficits, manual muscle test scores, and muscle tone scale
      assessment (p <.0001). The muscle tone scale findings showed a significant
      correlation with deformity (p <.0001), but did not correlate with manual muscle
      testing. ADLs were affected by muscle power and muscle tone independently.
      CONCLUSION: Adults with CP showed markedly increased muscle tone and moderate
      muscle weakness. These 2 factors did not correlate with each other, and were
      independently responsible for worse ADLs.

PMID- 11346842
TI  - Upper-limb function in Australian children with traumatic brain injury: A
      controlled, prospective study.
AB  - OBJECTIVE: To describe upper-limb function in children with mild and severe
      traumatic brain injury (TBI), by using both quantitative and qualitative
      measures. DESIGN: Controlled, prospective cohort study with assessment points
      initially, at 6 months, and at 2 years after TBI. SETTING: A tertiary pediatric
      trauma center in Australia. PATIENTS: Fifty-one children, ranging in age up to 14
      years, who were consecutive admissions with TBI. On the basis of initial and
      persisting abnormal coma score and persistence of posttraumatic amnesia, they
      were assigned to either a mild (n = 26) or a severely injured (n = 25) group.
      Thirty children admitted with non-TBI trauma were recruited as a control group.
      MAIN OUTCOME MEASURES: Quantitative measures included Bruininks-Oseretsky Test of
      Motor Proficiency and Peabody Developmental Motor Scales. Qualitative measures
      included Brunnstrom Recovery Stages (adapted), categoric scales of muscle tone,
      grasp used when handwriting, quality of writing product, bilateral activity, and
      splint use. RESULTS: There was little difference between the groups on the
      standardized assessments for subjects who could complete the tests. Qualitative
      measures showed the severe TBI group to have more difficulties with gross arm
      control, hand control, and hand function. CONCLUSION: Children with severe TBI
      experience more and persisting difficulties with upper-limb function. It is
      essential to include both quantitative and qualitative measures in this type of
      research.

PMID- 11346843
TI  - Reaching-lifting-placing task during standing after stroke: Coordination among
      ground forces, ankle muscle activity, and hand movement.
AB  - OBJECTIVE: To investigate the coordination among hand movement, ground forces,
      and muscle activity in standing stroke patients reaching forward and lifting an
      object from a table. DESIGN: Survey. SETTING: Research laboratory. PATIENTS:
      Eight stroke patients and 8 persons serving as controls. MAIN OUTCOME MEASURE:
      Symmetry of percentage of body weight (BW) during initial standing, velocity and
      hand path trajectory, ankle muscle electromyography. Temporal and spatial
      parameters in percentage of movement time were recorded by using 2 forceplates, 3
      dimensional kinematics, and surface electromyography. Motor function, sensory
      function, and functional performance were also assessed. RESULTS: Weight
      distribution during initial standing was significantly higher (57.4% +/- 8.1% BW)
      on the nonparetic leg. All subjects had preserved the preparatory loading phase,
      and after onset of hand movement loading shifted to the contralateral leg. Ankle
      muscle activity onset (lateral gastrocnemius [LG]) occurred after loading. In
      stroke subjects, LG was consistently activated first in the nonparetic leg,
      regardless of which arm performed the task. During paretic hand task, the
      reaching phase was significantly longer and the lifting phase significantly
      shorter compared with that of the nonparetic hand task and with that of the
      controls. In the paretic task, the hand path velocity was not bell-shaped; the
      object lifting was. CONCLUSIONS: Stroke subjects preserve the coordination
      between ground forces and hand movement. The lack of spontaneous use of the
      paretic hand is primarily caused by difficulties of planning the hand trajectory
      in space, as reflected by temporal and spatial parameters during task
      performance.

PMID- 11346844
TI  - Myoelectric manifestations of muscle changes in stroke patients.
AB  - OBJECTIVE: To evaluate the development of myoelectric fatigue in paretic and
      healthy tibialis anterior muscles of stroke patients. DESIGN: Case series.
      SETTING: Occupational therapy and clinical neurophysiology unit. PARTICIPANTS:
      Eight patients with hemiparesis or hemiplegia 9 months to 10 years poststroke.
      MAIN OUTCOME MEASURES: Current pulses of 0.1-ms width and 40-Hz repetition rate
      were applied for 10 seconds with a monopolar technique; myoelectric signals (M
      waves) were detected with surface electrodes. RESULTS: Mean values and initial
      values of the median frequency (MDF) between paretic and healthy side were
      statistically different, with the values on the healthy side much higher than the
      paretic side. Changes of MDF showed a decreasing pattern for both the paretic and
      the healthy sides, with the downslope of the curve of the healthy side more
      evident. CONCLUSIONS: In paretic muscles of stroke patients, the tendency toward
      atrophy of type II fibers appears to be frequent. Our study suggests this muscle
      rearrangement uses techniques much less invasive than muscle biopsy, and gives
      useful information about muscle function. This kind of information can help
      identify rehabilitation strategies, particularly for chronic stroke survivors.

PMID- 11346845
TI  - Differences in energy metabolism and neuromuscular transmission between 30-Hz and
      100-Hz stimulation in rat skeletal muscle.
AB  - OBJECTIVE: To examine differences in energy metabolism and neuromuscular
      transmission failure in rat hindlimb muscles subjected to electric stimulation at
      different frequencies. DESIGN: Experimental animal study. SETTING: Bioenergetic
      Research Center at Otsuka Pharmaceutical Company, Otsuka, Japan. ANIMALS: Thirty
      two 25-week-old male Wistar-Kyoto rats. INTERVENTIONS: With the rat under general
      anesthesia, the sciatic nerve was electrically stimulated at 30Hz and 100Hz to
      induce muscle contraction. MAIN OUTCOME MEASURES: Energy level and intracellular
      pH of muscles by phosphorus-31 magnetic resonance spectroscopy ((31)P-MRS); M
      wave amplitude of muscles by electromyography. RESULTS: During the first 4
      minutes under stimulation at 30Hz and at 100Hz, energy level and intracellular pH
      dropped to their lowest values (p <.05 or p <.01); the values then recovered with
      time. Recovery rates of energy level and intracellular pH during stimulation at
      100Hz were greater than those observed during stimulation at 30Hz. The M-wave
      amplitude during 100-Hz stimulation was permanently and significantly lower than
      that measured during 30-Hz stimulation (p <.01), and the recovery rate of M-wave
      amplitude after stimulation at 100Hz was slower than that after stimulation at
      30Hz. CONCLUSION: Neuromuscular transmission failure was greater with 100-Hz
      stimulation than with 30-Hz stimulation. This finding may account for the rapid
      recovery of energy level and intracellular pH that occurs with stimulation at
      100Hz.

PMID- 11346846
TI  - Phenol block of peripheral nerve conduction: Titrating for optimum effect.
AB  - OBJECTIVES: To verify the dose-response relationship in phenol nerve block and to
      determine the concentration and volume of phenol injectate required for effective
      nerve conduction block. DESIGN: Before-after, experimental study. SETTING: A
      research institute laboratory. ANIMALS: Seventy-one New Zealand white rabbits.
      INTERVENTIONS: Group I (n = 48) received tibial nerve block by perineural
      injection (phenol, n = 40; saline, n = 8), group II (n = 21) by submerging the
      nerve in phenol solution. The 6 subgroups of group I each received different
      concentrations (3%, 4%, 5%) and volumes (0.1mL, 0.2mL, 0.3mL). The 2 subgroups of
      group II received 3% (n = 8) and 5% (n = 13) phenol. MAIN OUTCOME MEASURES:
      Compound muscle action potential (CMAP) and tension of triceps surae muscles by
      electric stimulation of the sciatic nerve were measured preintervention and at
      day 1, and weeks 1, 2, 4, and 8 postblock. Histologic studies were performed on 2
      animals from group I. RESULTS: Two rabbits in group I died before results were
      obtained. In the remaining animals, CMAP amplitude reduced significantly (p <.05)
      as the volume of 5% phenol solution increased from 0.1mL, 0.2mL, to 0.3mL. A high
      concentration of phenol produced a more pronounced conduction block; however, no
      significant (p =.0589) difference existed among the 3 concentrations. Submerged
      tibial nerve had a greater degree of conduction block than perineurally injected
      nerve. Depth of the degeneration area in nerve fascicle varied with distance from
      the injection point. CONCLUSIONS: The nerve block effect of phenol can be
      titrated by adjusting the concentration and volume of phenol solution if the
      technique of application and localization of a block site are standardized.

PMID- 11346847
TI  - Quantifying swallowing function after stroke: A functional dysphagia scale based
      on videofluoroscopic studies.
AB  - OBJECTIVE: To develop a sensitive, specific scale for quantifying functional
      dysphagia in stroke patients, using results obtained from videofluoroscopic
      swallowing studies. DESIGN: Data collected from a serial oral and pharyngeal
      videofluoroscopic swallowing study. SETTING: A dysphagia clinic in a department
      of rehabilitation medicine at a tertiary care university hospital. PARTICIPANTS:
      One hundred three consecutively admitted stroke patients. INTERVENTIONS:
      Videoflurorscopy to measure a scale of 11 variables: lip closure score, bolus
      formation, residue in oral cavity, oral transit time, triggering of pharyngeal
      swallow, laryngeal elevation and epiglottic closure, nasal penetration, residue
      in valleculae, coating of pharyngeal wall after swallow, and pharyngeal transit
      time. MAIN OUTCOME MEASURES: Polychotomous linear logistic regression analysis of
      videofluoroscopic and aspiration results. Scale sensitivity and specificity, and
      the correlation between the total score of the scale and aspiration grade were
      analyzed. RESULTS: The scale's sensitivity and specificity for detecting
      supraglottic penetration and subglottic aspiration were 81%, 70.7%, and 78.1%,
      77.9%, respectively. A significant positive correlation was found between the
      scale's total score and the severity of aspiration (Spearman's r =.58943, p
      =.00001). CONCLUSION: This functional dysphagia scale, which was based on a
      videofluoroscopic swallowing study in stroke patients, is a sensitive and
      specific method for quantifying the severity of dysphagia.

PMID- 11346848
TI  - Cerebral venous thrombosis in young adults: 2 Case reports.
AB  - Cerebral venous thrombosis (CVT) is a disease with multiple known etiologies that
      present with a remarkably wide spectrum of clinical signs and symptoms. We
      present a case of a 34-year-old man with a history of meningeal symptoms for 1
      week after receiving a lumbar injection for lower back pain. He subsequently
      developed dense right hemiplegia and global aphasia. Head magnetic resonance
      imaging revealed superior sagittal sinus thrombosis. The patient was started on
      intravenous heparin but deteriorated neurologically. Urokinase infusion directly
      into the superior sagittal sinus was performed, with striking functional and
      neurologic improvement. Lupus anticoagulant was positive. We also present the
      case of a 24-year-old pregnant woman who developed an acute onset of meningeal
      symptoms and resultant left hemiparesis. Head magnetic resonance angiography
      revealed thrombosis of right transverse and sigmoid sinuses. Protein S deficiency
      was found. She was started on intravenous heparin, then enoxaparin, with
      improvement in symptoms. These cases demonstrate that CVT can be a cause of
      stroke in young patients with hypercoagability disorders, and a heightened
      awareness of CVT will promote optimal medical care and functional outcomes.
      Excellent functional recovery is likely with early recognition and treatment of
      the underlying etiology, as well as successful lysis of the clot.

PMID- 11346849
TI  - Tarlov cyst as a rare cause of S1 radiculopathy: A case report.
AB  - A 37-year-old female physician presented with a chief complaint of left posterior
      thigh pain, which began insidiously approximately 4 months before her initial
      examination. Initially, she had been evaluated by her physician, and magnetic
      resonance imaging (MRI) was ordered. The MRI scan was reported to be within
      normal limits, with the exception of minimal disc bulging at L4-5. She had
      received physical therapy with little benefit and was referred for physiatric
      assessment. Review of the patient's original MRI scan showed the presence of
      perineurial (Tarlov) cysts within the sacral canal at the level of S2, with
      compression of the adjacent nerve root. Subsequent electrodiagnostic testing
      showed axonal degeneration consistent with an S1 radiculopathy. Tarlov cysts can
      be a rare cause of lumbosacral radiculopathy and should be considered in the
      differential diagnosis of radicular leg pain.

PMID- 11346850
TI  - Using gabapentin to treat failed back surgery syndrome caused by epidural
      fibrosis: A report of 2 cases.
AB  - Failed back surgery syndrome (FBSS) is a long-lasting, often disabling, and
      relatively frequent (5%-10%) complication of lumbosacral spine surgery. Epidural
      fibrosis is among the most common causes of FBSS, and it is often recalcitrant to
      treatment. Repeated surgery for fibrosis has only a 30% to 35% success rate,
      whereas 15% to 20% of patients report worsening of their symptoms. Long-term
      outcome studies focusing on pharmacologic management of chronic back pain
      secondary to epidural fibrosis are lacking in the literature. This report
      presents 2 cases of severe epidural fibrosis managed successfully with gabapentin
      monotherapy. In both cases, functional status improved markedly and pain was
      significantly diminished. Gabapentin has an established, favorable safety profile
      and has been shown to be effective in various animal models and human studies of
      chronic neuropathic pain. Clinicians should consider gabapentin as a
      pharmacologic treatment alternative in the management of FBSS caused by epidural
      fibrosis.

PMID- 11346851
TI  - Midodrine for the management of orthostatic hypotension in patients with spinal
      cord injury: A case report.
AB  - A 21-year-old man sustained anterior displacement and a burst fracture of C7 in a
      motor vehicle crash. He underwent anterior corpectomy, decompression, fusion of
      C6-T1 vertebrae, and halo placement. The American Spinal Injury Association grade
      of his spinal cord injury (SCI) was C6 C tetraplegia. Severe orthostatic
      hypotension in the upright position complicated the patient's rehabilitation
      program. Midodrine was prescribed, and other medications with possible adverse
      effects were adjusted. Significant improvement after taking midodrine was
      reflected in the orthostatic vital signs and symptoms, as well as in FIM
      instrument scores. Staff noted improvements with therapy participation and
      functional status. The patient tolerated the midodrine well and had no
      significant side effects.

PMID- 11346852
TI  - Dysesthesia perceived as painful spasticity: A report of 3 cases.
AB  - Lesions of the central nervous system often involve the pyramidal tracts and the
      sensory pathways to produce spasticity, paresthesias, and dysesthesia. Three
      patients with intractable spasticity were treated with intrathecal baclofen. Two
      had an implanted Medtronic SynchroMed pump for long-term delivery of the muscle
      relaxant. The third patient had undergone a screening trial in which the baclofen
      was delivered into the intrathecal space through a lumbar catheter. All had
      excellent relief of spasms on clinical examination, but they reported painful
      spasms particularly at night. Two of the patients were successfully treated for
      dysesthesia.

PMID- 11346853
TI  - Delineation of clinical privileges in rehabilitation medicine.
AB  - The American Academy of Physical Medicine and Rehabilitation (AAPM&R) in 1995
      developed a list of 75 clinical privileges (in laundry-list format) that are
      typical of physiatric practice. This list has been used by some hospitals as a
      template for physiatric staff privileging. The National Association of Medical
      Staff Services has advocated a short list of core privileges, supplemented by a
      list of highly specialized procedures. To assess current practices in physiatric
      privileging, we surveyed 35 rehabilitation facilities. Results showed that 66%
      (20/30) of the respondents were not aware of the AAPM&R recommendations.
      Furthermore, we found an almost even split between facilities using core (16/30)
      versus laundry list (14/30) privileges. We also found evidence that the Joint
      Commission on Accreditation of Healthcare Organizations has recommended both
      types of approaches to different facilities in the recent past.

PMID- 11346854
TI  - Evaluation of a pushrim-activated, power-assisted wheelchair.
AB  - OBJECTIVE: To evaluate a novel pushrim-activated, power-assisted wheelchair
      (PAPAW) for compliance with wheelchair standards, metabolic energy cost during
      propulsion, and ergonomics during selected activities of daily living (ADLs).
      DESIGN: A 3-phase study, the second and third of which were repeated-measures
      designs. SETTING: A rehabilitation engineering center within a Veterans Affairs
      medical center. PATIENTS: Eleven full-time, community-dwelling, manual wheelchair
      users (4 women, 6 men) with spinal cord injuries or multiple sclerosis.
      INTERVENTIONS: Phase 1: Compliance testing, with a test dummy, in accordance with
      the wheelchair standards of the American National Standards Institute and the
      Rehabilitation Engineering and Assistive Technology Society of North America.
      Phase 2: Metabolic energy consumption testing-at 2 speeds and 3 resistance levels
      in subjects' manual wheelchair and the PAPAW. Phase 3: Evaluation of ability to
      perform ADLs and ergonomics of the PAPAW compared with the subjects personal
      wheelchair. MAIN OUTCOME MEASURES: Phase 1: The PAPAW's static stability, static
      strength, impact strength, fatigue strength, environmental response, obstacle
      climbing ability, range, maximum speed, and braking distance. Phase 2: Subjects'
      oxygen consumption per minute, minute ventilation, and heart rate during
      different speeds and workloads with a PAPAW and their own wheelchairs. Phase 3:
      Subject ratings of perceived comfort and basic ergonomics while performing
      selected ADLs. Completion time, stroke frequency, and heart rate during each ADL.
      RESULTS: Phase 1: The PAPAW was found to be in compliance with wheelchair
      standards. Phase 2: With the PAPAW, the user had a significantly lower oxygen
      consumption (&Vdot;O(2)mL/min: p <.0001; &Vdot;O(2)mL/kg x min: p <.0001) and
      heart rate (p <.0001) when compared with a manual wheelchair at different speeds.
      Phase 3: The PAPAW had a significantly higher mean ergonomic evaluation (p <.01)
      than the subjects' personal wheelchairs. The results of comparing the ratings of
      the car transfer between the PAPAW and the subjects' personal wheelchair showed a
      significant difference in the task of taking the wheels off (p <.001) and putting
      the wheels back on (p =.001), with the PAPAW receiving lower ratings. CONCLUSION:
      This study indicated that the PAPAW is compliant with wheelchair standards,
      reduces the energy demand placed on the user during propulsion, and that subjects
      rated its ergonomics favorably when compared with their personal wheelchair.
      PAPAWs may provide manual wheelchairs with a less physiologically stressful means
      of mobility with few adaptations to the vehicle or home environment.

PMID- 11346855
TI  - Knee bracing after ACL reconstruction.

PMID- 11346857
TI  - A bibliography of cost-effectiveness practices in physical medicine and
      rehabilitation: AAPM&R white paper.
AB  - Cost-effectiveness studies attempt to determine the ratio of costs to outcomes of
      a particular intervention or treatment and to compare a standard intervention
      with an alternative intervention to determine if the alternative is more cost
      effective. The goal is to establish priorities for the resources allocation and
      to decide among alternative interventions for the same medical condition. The
      global process of rehabilitation does not usually lend itself to cost-effective
      analysis (due to the complex set of treatments provided) but rather to specific
      interventions and specific aspects of outcome. The American Academy of Physical
      Medicine and Rehabilitation has published a cost effectiveness annotated
      bibliography on the Internet (http://www.aapmr.org/memphys/cebfinala.htm) that
      identifies 132 studies in the literature that meet specified criteria and are
      related to the field of rehabilitation. This White Paper attempts to interpret
      and synthesize the studies in that bibliography that relate to stroke, spinal
      cord injury (SCI), orthopedic conditions, pain syndromes, amputations, and
      traumatic brain injury (TBI). Most studies support the cost effectiveness of care
      for stroke and SCI in dedicated units or centers rather than in a general medical
      unit. Studies also support back programs and revascularization procedures in limb
      ischemia. Studies in TBI underscore the significant financial resources for the
      care of these patients as well as the potential benefit from rehabilitation
      services even in the most severely injured. Further high quality research in this
      area is needed.

PMID- 11346858
TI  - Unmet needs in metastatic bone disease and its complications: is progress
      possible?

PMID- 11346859
TI  - Chemical and biological prerequisites for novel bisphosphonate molecules: results
      of comparative preclinical studies.
AB  - While all bisphosphonates have a common basic structure, differences in
      substituents strongly influence the pharmacologic properties of these compounds.
      A large number of bisphosphonate analogs were evaluated in an effort to identify
      a new, high-potency, bisphosphonate that would meet the chemical and biological
      requirements for a potentially effective and safe antiresorptive treatment.
      Important parameters that were evaluated included inhibition of bone resorption,
      lack of effect on bone mineralization, tolerability (particularly renal),
      molecular mechanism of action, and the ability to prevent bone changes associated
      with estrogen deficiency. Zoledronic acid (Zometa; Novartis Pharmaceuticals Corp,
      East Hanover, NJ), a bisphosphonate characterized by an imidazole substituent,
      was selected for further development based on its potent antiresorptive effects
      in vitro and in vivo, minimal inhibition of bone mineralization, and improved
      therapeutic ratio (antiresorptive effects v renal tolerability). Zoledronic acid
      was 2 to 3 orders of magnitude more potent than pamidronate in bone resorption
      assays, but showed a 3-fold greater renal tolerability than pamidronate. Like
      other nitrogen-containing bisphosphonates, zoledronic acid inhibits protein
      prenylation in osteoclasts, confirming a molecular basis for its pharmacologic
      activity. In long-term animal studies in ovariectomized rats and monkeys,
      zoledronic acid was able to prevent all the bone changes associated with estrogen
      deficiency. These studies provided support for further clinical development of
      this compound in both benign and malignant diseases characterized by excessive
      bone resorption.

PMID- 11346860
TI  - The role of zoledronic acid in cancer: clinical studies in the treatment and
      prevention of bone metastases.
AB  - Preclinical studies with zoledronic acid (Zometa; Novartis Pharmaceuticals Corp,
      East Hanover, NJ) have shown its potential in malignant bone disease. Clinical
      studies in the treatment of hypercalcemia of malignancy have been completed, as
      have phase I and II trials in patients with cancer and pre-existing bone
      metastases. Three randomized, double-blind, controlled phase III trials are
      ongoing to establish the efficacy and safety of zoledronic acid in the treatment
      of osteolytic and osteoblastic bone metastases. In one study, 4 mg zoledronic
      acid is compared with the standard therapy, 90 mg pamidronate, in treatment of
      osteolytic lesions in patients with breast cancer and multiple myeloma. Two other
      studies, one in patients with prostate cancer and bone metastases and another in
      patients with non-small cell lung cancer and other tumor types, are placebo
      controlled. The primary end point in all three studies is the frequency of
      skeletal complications resulting from bone metastases. Adjuvant trials that
      assess the ability of zoledronic acid to prevent or reduce the incidence of bone
      metastases in patients at high risk for future skeletal metastasis are also
      planned or ongoing. The rationale and design of these ongoing and planned studies
      is discussed.

PMID- 11346861
TI  - Zoledronic acid in the treatment of hypercalcemia of malignancy: results of the
      international clinical development program.
AB  - This report summarizes results of the clinical development program evaluating
      zoledronic acid (Zometa; Novartis Pharmaceuticals Corp, East Hanover, NJ) in the
      treatment of hypercalcemia of malignancy (HCM). In addition to a phase I dose
      escalation trial, two randomized, double-blind, double-dummy studies were
      conducted in parallel to investigate the clinical efficacy and safety of 4 mg and
      8 mg zoledronic acid in patients with moderate to severe HCM. Patients were
      treated with a single dose of zoledronic acid (4 or 8 mg) via 5-minute infusion
      or a control treatment, 90 mg pamidronate via 2-hour infusion. Patients who
      relapsed or had refractory HCM after initial treatment could be re-treated with 8
      mg zoledronic acid. End points included rate of complete response, defined as
      normalization of corrected serum calcium by day 10, change in corrected serum
      calcium, time to relapse, duration of response, and bone biochemical markers.
      Doses of > or =0.02 mg/kg were effective and nontoxic in the phase I study. In
      the controlled studies, 287 patients were randomized and evaluated for safety and
      275 patients were evaluable for efficacy. The proportions of patients with a
      complete response by day 10 were 88.4% and 86.7% in the 4 mg and 8 mg zoledronic
      acid groups, respectively, compared with 69.7% in the 90 mg pamidronate group.
      Corrected serum calcium normalization occurred by day 4 in 45.3% of patients
      treated with 4 mg zoledronic acid, 55.6% of patients treated with 8 mg zoledronic
      acid, and 33.3% of patients treated with pamidronate. Mean change from baseline
      in corrected serum calcium also was greater with zoledronic acid than with
      pamidronate. Median times to relapse were significantly longer in both the
      zoledronic acid 4 mg and 8 mg groups compared with the pamidronate group. There
      were no significant differences in efficacy between the 4 mg and 8 mg zoledronic
      acid doses. Retreatment in 69 patients with relapsing or refractory hypercalcemia
      with 8 mg zoledronic acid resulted in a 52% complete response rate. Fever,
      hypophosphatemia, and asymptomatic hypocalcemia were the most common drug-related
      adverse events. These studies have shown that a short single intravenous dose of
      4 mg or 8 mg zoledronic acid is effective in treating moderate to severe HCM.
      Zoledronic acid produced a higher rate of calcium normalization, faster onset of
      action, and longer time to relapse than pamidronate, while maintaining an
      excellent safety profile. The lower dose of 4 mg is recommended as initial
      therapy, with the 8 mg dose reserved for patients requiring retreatment.

PMID- 11346862
TI  - Zoledronic acid in cancer patients with bone metastases: results of Phase I and
      II trials.
AB  - Zoledronic acid (Zometa, Novartis Pharmaceuticals Corp, East Hanover, NJ) is a
      new, highly potent bisphosphonate that may provide improved management of
      skeletal complications in cancer patients with bone metastases. A total of 383
      cancer patients with osteolytic bone lesions was evaluated in two phase I studies
      and one phase II study of zoledronic acid. The phase I studies used two dosing
      regimens, either a 5-minute monthly intravenous infusion of 0.1 to 8 mg
      administered for 3 or more months or a single 30 to 60 second intravenous bolus
      of 1 to 16 mg. Zoledronic acid was well tolerated in the two phase I studies and
      a maximum tolerated dose was not reached in either study. A dose-dependent
      decrease in urinary markers of bone resorption was observed with the monthly 5
      minute infusion. A single intravenous bolus of doses ranging from 2 to 16 mg
      zoledronic acid suppressed biochemical markers of bone resorption for up to 8
      weeks. The phase II study evaluated a 5-minute infusion of 0.4, 2, or 4 mg
      zoledronic acid and a 2-hour infusion of 90 mg pamidronate in 280 patients with
      bone metastases and multiple myeloma or breast cancer. Significantly fewer
      patients receiving the 2 and 4 mg doses of zoledronic acid or 90 mg pamidronate
      required radiation therapy to bone than those patients receiving a 0.4 mg dose of
      zoledronic acid. Only 30% to 35% of patients in the 2 and 4 mg zoledronic acid
      groups or in the pamidronate group experienced any skeletal related event
      compared with 46% in the 0.4 mg zoledronic acid group. Adverse events consistent
      with an acute phase reaction were observed with both bisphosphonates. No new,
      unexpected adverse events were observed with this novel bisphosphonate. These
      studies support the further evaluation of zoledronic acid in cancer patients with
      osteolytic metastases. Doses of 0.4 mg or less are ineffective, while rapid
      infusion of more than 8 mg may increase the risk of renal dysfunction. A 4 mg
      dose given as a brief infusion appears to offer an excellent benefit/risk ratio
      for further evaluation in phase III trials.

PMID- 11346863
TI  - Preclinical studies with zoledronic acid and other bisphosphonates: impact on the
      bone microenvironment.
AB  - The propensity for breast cancer cells to metastasize to bone and to induce
      osteolysis has long been recognized. Characteristics of both the tumor cells and
      the bone microenvironment contribute to this phenomenon. The presence of tumor in
      bone is associated with activation of osteoclasts, resulting in excessive bone
      resorption and subsequent osteolysis. Breast cancer cells and other tumor types
      influence osteoclastic bone resorption by increasing the number of osteoclasts
      and enhancing their resorptive activity. Parathyroid hormone-related peptide, in
      addition to its role in humorally mediated hypercalcemia, is secreted by
      metastatic breast cancer cells in bone in which it acts as a paracrine factor to
      stimulate osteoclasts. As bone matrix is broken down by activated osteoclasts, a
      rich supply of mitogenic factors is released, including insulin-like growth
      factors, bone morphogenetic proteins, and fibroblast growth factors. Transforming
      growth factor (TGF)-beta, one of the most abundant of the bone-derived factors,
      promotes increased production of parathyroid hormone-related peptide by tumor
      cells, establishing a "vicious cycle" leading to progressive tumor growth and
      bone destruction. Bisphosphonates interrupt this cycle by inhibiting osteoclasts,
      in part by inducing osteoclast apoptosis. In several animal models of breast
      cancer metastasis to bone, bisphosphonates decrease the number of new bone
      metastases and inhibit progression of existing lesions. A single 3 microg
      intravenous injection of zoledronic acid (Zometa; Novartis Pharmaceuticals Corp,
      East Hanover, NJ), a new highly potent bisphosphonate, prevented destruction of
      trabecular bone in an orthotopic mouse mammary tumor model. Tumor volume in bone
      was decreased by zoledronic acid in a dose-dependent manner in the same model,
      and tumor cell apoptosis was increased by zoledronic acid in bone metastases in
      the 4T1 murine model of mammary carcinoma metastasis. Zoledronic acid at a dose
      of 1.0 microg/d for 10 days also reduced bone lesion area in a nude mouse model
      with existing bone metastases. Although bisphosphonates, including zoledronic
      acid, are able to induce apoptosis in tumor cells in vitro, studies in animal
      models to date have generally not shown a reduction in nonosseous tumor.
      Therefore, bisphosphonate-associated tumor reduction in bone is most likely
      mediated by osteoclast inhibition or is related to high local concentrations of
      bisphosphonates in the bone compartment.

PMID- 11346864
TI  - Zoledronic acid: an evolving role in the treatment of cancer patients with bone
      disease.

PMID- 11346865
TI  - A case-control study of unilateral and bilateral breast carcinoma patients.
AB  - BACKGROUND: Women with unilateral breast carcinoma are at increased risk for
      developing contralateral disease. The clinical significance of bilateral breast
      carcinoma has not been fully defined, and the subset of patients who may benefit
      from medical or surgical risk-reduction intervention has not yet been
      characterized. The purpose of this study was to evaluate risk factors and
      outcomes for bilateral breast carcinoma. METHODS: A subject group of 70 bilateral
      breast carcinoma patients (62% metachronous) was matched by age and survival
      interval with a control group of 70 unilateral breast carcinoma patients. Median
      follow-up was 103 months. RESULTS: Eighty-two percent of the unilateral patients
      and 80% of the bilateral patients had Stage I or II disease at diagnosis. Median
      age at presentation was 53 years. In the bilateral group, the contralateral
      cancer was diagnosed at the same or earlier stage than the first cancer in 87% of
      cases. Bilateral patients were significantly more likely to have multicentric
      disease and to have a positive family history for breast carcinoma compared with
      the unilateral group. There were no significant differences regarding history of
      exogenous hormone exposure, lobular histology, hormone-receptor status, or HER
      2/neu expression. Five-year disease-free survival was 94% for the unilateral
      breast carcinoma patients and 91% for the bilateral breast carcinoma patients (P
      = 0.16). CONCLUSIONS: Survival for patients with bilateral breast carcinoma is
      similar to that of patients with unilateral disease; however, prophylactic risk
      reduction intervention for the contralateral breast should be considered in
      patients who have multicentric unilateral disease or a positive family history
      for breast carcinoma.

PMID- 11346866
TI  - A prospective prognostic study of the hormonal milieu at the time of surgery in
      premenopausal breast carcinoma.
AB  - BACKGROUND: Despite numerous studies, the influence of timing at surgery in
      relation to the menstrual cycle on the prognosis of breast carcinoma is still
      controversial. Most studies are retrospective, and the reliability of the
      menstrual history data is limited by the lack of hormonal assessment at the time
      of surgery. The authors prospectively studied the influence of the menstrual
      cycle phase as determined by circulating hormones at the time of surgery on the
      outcome of breast carcinoma. METHODS: A population of 360 premenopausal women
      with nonmetastatic breast carcinoma operated on from 1992 to 1995 was analyzed.
      Serum estradiol, progesterone, follicle-stimulating hormone (FSH), and
      luteinizing hormone (LH) levels were assayed the day of surgery to define the
      menstrual cycle phase (follicular, n = 186; ovulatory, n = 24; luteal, n = 150).
      The mean follow-up was 48 months. RESULTS: There were no relations between the
      menstrual phase at surgery and tumor size, cathepsin D level, Scarff-Bloom
      Richardson grade, Pg receptor (PgR), and the number of positive lymph nodes. The
      mean estrogen receptor level was higher during the follicular phase than in the
      ovulatory and luteal phases (P < 0.02). Univariate analysis of recurrence free
      survival (RFS) and overall survival (OS) showed no relations with the menstrual
      phase or the level of estradiol and progesterone at the time of surgery. High LH
      or FSH levels (above the medians) were associated with shorter RFS (P = 0.02 and
      P = 0.04, respectively) or OS (P < or = 0.01 and P = 0.01, respectively). In
      multivariate analysis, lymph node status, PgR status and LH level were the most
      significant parameters for predicting OS. There appeared to be no survival
      differences between menstrual cycle groups after stratification by lymph node
      status. CONCLUSIONS: This prospective study showed a lack of prognostic value of
      timing at surgery in relation to the menstrual period or to estrogen and
      progesterone levels in premenopausal breast carcinoma. Conversely, high
      gonadotropin levels could predict OS independently of other prognostic factors.

PMID- 11346867
TI  - Lobular carcinoma in situ increases the risk of local recurrence in selected
      patients with stages I and II breast carcinoma treated with conservative surgery
      and radiation.
AB  - BACKGROUND: Lobular carcinoma in situ (LCIS) is a known risk factor for the
      development of invasive breast carcinoma. However, little is known regarding the
      impact of LCIS in association with an invasive carcinoma on the risk of an
      ipsilateral breast tumor recurrence (IBTR) in patients who are treated with
      conservative surgery (CS) and radiation therapy (RT). The purpose of this study
      was to examine the influence of LCIS on the local recurrence rate in patients
      with early stage breast carcinoma after breast-conserving therapy. METHODS:
      Between 1979 and 1995, 1274 patients with Stage I or Stage II invasive breast
      carcinoma were treated with CS and RT. The median follow-up time was 6.3 years.
      RESULTS: LCIS was present in 65 of 1274 patients (5%) in the study population.
      LCIS was more likely to be associated with an invasive lobular carcinoma (30 of
      59 patients; 51%) than with invasive ductal carcinoma (26 of 1125 patients; 2%).
      Ipsilateral breast tumor recurrence (IBTR) occurred in 57 of 1209 patients (5%)
      without LCIS compared with 10 of 65 patients (15%) with LCIS (P = 0.001). The 10
      year cumulative incidence rate of IBTR was 6% in women without LCIS compared with
      29% in women with LCIS (P = 0.0003). In both groups, the majority of recurrences
      were invasive. The 10-year cumulative incidence rate of IBTR in patients who
      received tamoxifen was 8% when LCIS was present compared with 6% when LCIS was
      absent (P = 0.46). Subsets of patients in which the presence of LCIS was
      associated with an increased risk of breast recurrence included tumor size < 2 cm
      (T1), age < 50 years, invasive ductal carcinoma, negative lymph node status, and
      the absence of any adjuvant systemic treatment (chemotherapy or hormonal therapy)
      (P < 0.001). LCIS margin status, invasive lobular carcinoma histology, T2 tumor
      size, and positive axillary lymph nodes were not associated with an increased
      risk of breast recurrence in these women. CONCLUSIONS: The authors conclude that
      the presence of LCIS significantly increases the risk of an ipsilateral breast
      tumor recurrence in certain subsets of patients who are treated with breast
      conserving therapy. The risk of local recurrence appears to be modified by the
      use of tamoxifen. Further studies are needed to address this issue.

PMID- 11346868
TI  - Apoptosis in rectal carcinoma: prognosis and recurrence after preoperative
      radiotherapy.
AB  - BACKGROUND: Rectal carcinoma is common, with considerable local recurrence and
      death rates. Preoperative radiotherapy and refined surgical techniques can
      improve local control. The aim of this study was to investigate the interaction
      between apoptosis and the outcome of rectal carcinoma, with and without short
      term preoperative radiotherapy. METHODS: Specimens were from 162 patients from
      the Southeast Swedish Health Care region included in the Swedish Rectal Cancer
      Trial between 1987-1990. New sections from the paraffin blocks of the
      preoperative biopsies and the surgical specimens were examined for apoptosis
      using the terminal deoxynucleotidyl transferase mediated digoxigenin nick end
      labeling (TUNEL) method. RESULTS: The mean percentage of apoptotic cells was 0.3%
      (0-4%) and 1.1% (0-14.5%) for the preoperative biopsy and the surgical specimen,
      respectively. The authors analyzed the surgical specimens from nonirradiated
      patients and divided them into three groups by apoptotic index (AI) as follows:
      0%, 0-1%, and > 1%. A high AI was associated with a decreased local recurrence
      rate compared with an intermediate or a low AI (P = 0.024). There was no
      significant relation between AI and survival. There was a significant reduction
      in the local recurrence rate for irradiated patients compared with the
      nonirradiated in the low (P = 0.015) and intermediate (P = 0.038) AI groups. In
      the high AI group, there were few recurrences and no significant difference was
      observed between irradiated and nonirradiated patients. The relative risk of
      death from rectal carcinoma in Dukes A-C patients was not significantly decreased
      by radiotherapy, but, in the intermediate AI group, there was a trend (P = 0.08)
      in favor of the irradiated patients. CONCLUSION: A high AI in rectal carcinoma
      indicated a decreased local recurrence rate.

PMID- 11346869
TI  - Depth of invasion parallels increased cyclooxygenase-2 levels in patients with
      gastric carcinoma.
AB  - BACKGROUND: Nonsteroidal anti-inflammatory drugs may reduce the incidence of
      intestinal carcinoma, presumably through inhibition of cyclooxygenase-2 (COX-2).
      The authors correlated tumor expression of COX-2 with clinicopathologic features
      in tissues from patients with gastric carcinoma. METHODS: Thirty-three surgical
      specimens, including carcinomas and corresponding noncancerous mucosa, were
      sampled. Reverse transcription-polymerase chain reaction analysis was performed
      concomitantly for COX-1 and COX-2. A COX-2 index was determined from the band
      density ratio of COX-2 to constitutively expressed COX-1. Immunohistochemical
      staining with COX-2 antibody and routine histologic assessment were performed in
      the same specimens. RESULTS: The COX-2 index in gastric carcinoma was
      significantly higher than in normal mucosa (3.4 +/- 0.7 vs. 2.2 +/- 0.7; P <
      0.05). COX-2 indices were significantly higher in gastric carcinoma tissues with
      deep invasion; indices for pT1, pT2, pT3, and pT4 carcinomas were 0.8 +/- 0.3,
      2.8 +/- 0.5, 4.3 +/- 1.0, and 8.8 +/- 5.5, respectively (P < 0.05).
      Immunohistochemistry demonstrated COX-2 protein diffusely in the cytoplasm of
      tumor cells but not in surrounding stroma or in noncancerous mucosa. CONCLUSIONS:
      COX-2 mRNA expression in gastric carcinoma tissue is correlated closely with
      depth of invasion, indicating that COX-2 is involved in the growth of gastric
      carcinoma.

PMID- 11346870
TI  - MAGE, BAGE, and GAGE gene expression in patients with esophageal squamous cell
      carcinoma and adenocarcinoma of the gastric cardia.
AB  - BACKGROUND: The MAGE, BAGE, and GAGE gene families code for distinct, tumor
      specific antigens that are recognized by cytotoxic T lymphocytes in the context
      of HLA molecules. The purpose of this study was to analyze MAGE, BAGE, and GAGE
      gene expression in the two major histologic types of esophageal carcinoma,
      squamous carcinoma (ESCc) and adenocarcinoma (CAc), and to correlate their
      expression patterns with the principal prognostic parameters and long term
      survival. METHODS: Gene expression was analyzed in surgical samples from 24
      patients with ESCc and 24 patients with CAc by reverse transcriptase-polymerase
      chain reaction amplification (RT-PCR). None of the patients had received
      preoperative chemotherapy or radiotherapy, and all were followed until death or
      for a minimum of 4 years. RESULTS: Sixteen ESCc samples (67%) and 9 CAc samples
      (37.5%) expressed at least one of the genes under study. The expression of each
      MAGE gene in the two histologic types was not significantly different, with the
      exception of MAGE-4, which was expressed more in ESCc samples than in CAc
      samples. BAGE and GAGE expression was rather low and, in every case, was
      associated with the expression of at least one MAGE gene. CONCLUSIONS: In the
      group as a whole, and in both ESCc and CAc subgroups, no significant correlation
      emerged between the expression of any gene and prognostic parameters, such as
      pathologic tumor, lymph node, or disease stage. Nevertheless, BAGE or GAGE
      expression was related significantly to a poor prognosis, whereas the expression
      of MAGE genes (in the absence of BAGE and GAGE expression) was related
      significantly to a good prognosis.

PMID- 11346871
TI  - Hypogonadism following prostate-bed radiation therapy for prostate carcinoma.
AB  - BACKGROUND: The degree of testicular damage resulting from primary treatment of
      prostate carcinoma by external beam radiation therapy (EBRT) to the prostate bed
      has not been determined. If significant testicular damage has occurred, the
      resulting endocrine changes may result in modified tumor behavior, contribute to
      postradiation impotence, and may aggravate other signs and symptoms of
      hypogonadism, potentially influencing a patient's choice of primary treatment for
      his tumor. METHOD: Three to eight years after primary treatment for localized
      prostate carcinoma, serologic evaluation for hypogonadism was undertaken in 33
      men who had received EBRT and in 55 similar men who had received radical
      prostatectomy (RP). No subjects had developed recognized tumor recurrence, and
      none had undergone hormonal treatment since primary therapy. RESULTS: Among men
      of similar age, prior treatment with EBRT was associated with significantly more
      frequent hypogonadism than prior treatment with RP. In men with EBRT, total
      testosterone levels averaged 27.3% less, free testosterone levels 31.6% less,
      dihydrotestosterone levels 33.4% less, luteinizing hormone (LH) levels 52.7%
      greater, and follicle-stimulating hormone (FSH) levels 100% greater than those
      values in men who had prior treatment with RP. Differences between postradiation
      and postsurgical men in LH and FSH levels were most prominent in men older than
      70 years. CONCLUSIONS: Three to eight years after primary treatment for prostate
      carcinoma, striking hormone differences were present between men who had received
      EBRT to the prostate bed and those with prior RP. These differences strongly
      suggested that prominent and permanent testicular damage was sustained during
      EBRT, frequently severe enough to cause hypogonadism.

PMID- 11346872
TI  - Prognostic significance of frequent acidophilic nuclear inclusions in
      adenocarcinoma of the lung with immunohistochemical and ultrastructural studies.
AB  - BACKGROUND: Adenocarcinoma of the lung occasionally has acidophilic nuclear
      inclusions (ANIs). Some studies have reported that the incidence of ANIs was
      higher in well differentiated tumor types and have suggested that adenocarcinoma
      patients with ANIs might have a more favorable prognosis; however, to the
      authors' knowledge, statistically significant prognostic findings were not
      reported. The objective of the current study was to assess the prognostic
      significance of ANI in patients with pulmonary adenocarcinoma and, moreover, to
      characterize ANI immunohistochemically and ultrastructurally. METHODS: Surgically
      resected tumor specimens from 147 patients with primary pure adenocarcinoma of
      the lung were examined. Only obvious ANIs surrounded by a clear halo on
      hematoxylin and eosin-stained slides were counted; the authors classified cases
      with > or = 10 ANIs per 10 high-power fields (/10 HPF) as frequent-ANI cases,
      cases with < 10 ANIs/10 HPF as infrequent-ANI cases, and cases without ANIs as
      non-ANI cases in the current study. RESULTS: Nineteen frequent-ANI cases (12.9%)
      and 16 infrequent-ANI cases (10.9%) were found; the remaining 112 cases (76.2%)
      were considered to be non-ANI cases. The majority of ANIs immunohistochemically
      contained surfactant apoprotein and ultrastructurally corresponded to
      invagination of the inner nuclear membrane, showing a tubular or amorphous
      configuration. Frequent-ANI patients showed significantly better prognosis than
      the other two groups on both overall univariate analysis and univariate analysis
      limited to patients with International Union Against Cancer Stage I disease (P =
      0.0096 and P = 0.0095, respectively). However, on the multivariate analysis only
      disease stage was shown to be a significant prognostic factor and frequent-ANI
      showed borderline significance (P = 0.0956). CONCLUSIONS: Frequent ANIs appear to
      be of limited value in clarifying the prognosis of patients with lung
      adenocarcinoma.

PMID- 11346873
TI  - Metabolic activity and clinical features of primary ganglioneuromas.
AB  - BACKGROUND: Ganglioneuroma (GN) is considered by most to be a benign tumor of
      neural crest origin. It may evolve from differentiating neuroblastoma or may be
      diagnosed as primary ganglioneuroma. The rarity of this tumor and the lack of
      understanding of its biology often lead to inaccurate diagnosis and treatment.
      METHODS: The authors analyzed clinical features and biologic behavior of primary
      ganglioneuroma in 49 patients who were registered with but were not part of the
      national neuroblastoma trials. Data included age and symptoms at diagnosis,
      gender, tumor localization and size, (123)I-metaiodobenzylguanidine (mIBG)
      scintigraphy, secretion of catecholamines, histology, treatment, and outcome,
      whenever available. RESULTS: Patients with primary ganglioneuroma were
      significantly older than patients with neuroblastoma. Median age at diagnosis was
      79 months compared with 16 months (P < 0.0001). Ganglioneuroma were equally
      distributed between males and females (1.13:1). A preference of thoracic (41.5%)
      and abdominal, nonadrenal tumors (37.5%) was observed compared with adrenal GN
      (21%). At diagnosis, thoracic tumors appeared larger than nonthoracic ones. Local
      lymph node metastases occurred in two patients. One ganglioneuroma had
      metastasized to soft tissues. (123)I-mIBG scintigraphy detected mIBG uptake at
      tumor site in 57% of the GN tumors. Levels of catecholamines in plasma and/or
      urine were increased in 39%. Slight immaturity of ganglion cells was observed in
      93% of all ganglioneuroma tumors. None of the 22 tumors analyzed exhibited MYCN
      gene alterations. Although 12 patients had macroscopic residuals, no tumor
      progression or recurrence was observed in a median follow-up of 25 months.
      CONCLUSIONS: Ganglioneuroma may present with metabolic activity such as increased
      secretion of catecholamines and/or mIBG uptake. There are no specific diagnostic
      signs or symptoms discriminating ganglioneuroma and neuroblastoma tumors.
      Therefore, ganglioneuroma requires tissue investigation for diagnosis. Prognosis
      after surgical resection without further therapy seems to be excellent.

PMID- 11346874
TI  - Predictive value of grade for metastasis development in the main histologic types
      of adult soft tissue sarcomas: a study of 1240 patients from the French
      Federation of Cancer Centers Sarcoma Group.
AB  - BACKGROUND: Histologic grade is said to be the most important prognostic factor
      in adult soft tissue sarcomas (STS), but most grading systems have been tested in
      the overall sarcoma group and the predictive value of histologic grade needs to
      be assessed specifically for each of the histologic categories. METHODS: From
      1980 to 1994, 1240 nonmetastatic patients were entered in the French STS
      database. The following parameters were studied: patient's age and gender,
      previous history, tumor location, size and depth, neurovascular or bone
      involvement (NBI), histologic type and subtype, and grade (the French Federation
      of Cancer Centers [FNCLCC] system). Median follow-up for the survivors was 88
      months; only 5% of patients were lost to follow-up. The authors performed
      univariate and multivariate analyses for metastasis-free survival for the overall
      sarcoma group and for every main histologic type. RESULTS: In order of
      importance, parameters were respectively retained as independent predictors of
      metastasis as follows: grade, tumor size, NBI and tumor depth for the overall
      group, grade and NBI for malignant fibrous histiocytomas (n = 349), tumor size,
      histologic subtype and grade for liposarcomas (n = 188), NBI, grade and tumor
      size for leiomyosarcomas (n = 148), grade and NBI for synovial sarcomas (n =
      125), grade for unclassified sarcomas (n = 140), and sarcomas of other types (n =
      158). No parameter was significant for malignant schwannomas (n = 72) or for
      rhabdomyosarcomas (n = 60). CONCLUSION: In this study, histologic grade appeared
      as an independent predictor of metastasis development in the main histologic
      types of adult STS, with the exception of malignant schwannomas and
      rhabdomyosarcomas.

PMID- 11346875
TI  - Trisomy 6 in basal cell carcinomas correlates with metastatic potential: a dual
      color fluorescence in situ hybridization study on paraffin sections.
AB  - BACKGROUND: Most basal cell carcinomas (BCCs) are indolent lesions; a few become
      locally aggressive or even metastatic. Little is known about the molecular and
      genetic alterations in this malignant transformation. Conventional karyotyping in
      BCC has revealed a high frequency of nonclonal, structural rearrangements, with
      few cases that show multiple, unrelated, small clones suggestive of a
      multicellular origin. Trisomy 6 was described recently in a few BCCs, but the
      biologic significance of the appearance of trisomy 6 in BBCs was not clear.
      METHODS: Thirty cases including 4 metastatic, 4 locally aggressive, and 22
      conventional nonaggressive BCCs were studied. Fluorescence in situ hybridization
      (FISH) was performed on 4 microm tissue sections, using alpha-centromeric
      enumeration probes for chromosome 6 (SpectrumGreen, Vysis Inc., Downers Grove,
      IL) and chromosome 4 (SpectrumOrange, Vysis Inc., Downers Grove, IL, used as
      disomic cell control). Trisomy 6 was semiquantitated within tumor cells and
      nonneoplastic cells in each case. RESULTS: Trisomy 6 was identified in all 4
      metastatic BCCs within tumor cells and in corresponding BCCs at the primary
      cutaneous site in 2 of these 4 cases. Two locally aggressive BCCs, 1 of which had
      preceding radiation exposure, also showed trisomy 6. All nonaggressive BCCs and
      nonneoplastic cells were disomic for chromosome 6. CONCLUSIONS: Trisomy 6 has
      been identified as a cytogenetic aberration representative of tumor cells in
      aggressive and metastatic BCC. None of the nonaggressive BCCs in this study
      demonstrated trisomy 6. Acquisition of trisomy 6 by tumor cells in BCC may lead
      to the emergence of metastatic potential. Additional studies to define the
      underlying mechanisms may be valuable in preventing aggressive behavior in BCC.

PMID- 11346876
TI  - Endothelin-1 in human prostatic carcinoma treated with androgen withdrawal: an
      immunohistochemical study.
AB  - BACKGROUND: Various reports suggest a role for endothelin-1 in prostatic
      carcinoma. The objective of the current study was to evaluate the changes of the
      immunodetectable endothelin-1 in prostatic carcinomas characterized by different
      grades of regression due to total androgen withdrawal. METHODS: An
      immunohistochemical study was made on eleven prostatic carcinomas treated with
      neoadjuvant hormonal therapy for 3 months, followed by radical prostatectomy.
      Another ten specimens of untreated carcinomas were studied for comparison. An
      appraisal of androgen receptors was associated. A highly specific polyclonal
      antibody against endothelin-1 and a commercial monoclonal mouse antibody for
      androgenic receptors were used. RESULTS: In all cases, a prevalent quantity of
      androgenic receptor-positive tumor cells were present. Neoplastic cells of
      untreated carcinomas showed a strong and heterogeneous staining for endothelin 
      1. In unregressed areas of treated cases, the features of endothelin-1 and
      androgen-receptor staining were the same as those of untreated cases. In areas
      characterized by moderate histologic regression, the endothelin-1 staining became
      more heterogeneous. In areas of strong histologic regression, a diffuse membrane
      staining was often noted. Only in completely regressed cancer cells was a
      definite loss of immunodetectable endothelin-1 and androgenic receptors observed.
      CONCLUSIONS: Endothelin-1 is one of the proteins intrinsic to prostatic
      epithelial cells, both benign and malignant. In cases treated with androgen
      withdrawal, histologic regression is not uniform. In unmodified areas,
      immunodetectable endothelin-1 and androgenic receptors also are unmodified, thus
      suggesting some mechanism that substitutes for the action of androgen. Only
      neoplastic cells with complete histologic regression also lose androgenic
      receptors and endothelin-1, whereas the preserved immunostaining in deeply
      modified prostatic neoplastic cells seems to indicate that these cells still are
      potentially active.

PMID- 11346877
TI  - Expression of P-glycoprotein, multidrug resistance-associated protein 1, and lung
      resistance-related protein in human soft tissue sarcomas before and after
      hyperthermic isolated limb perfusion with tumor necrosis factor-alpha and
      melphalan.
AB  - BACKGROUND: Multidrug resistance (MDR) is associated with expression of P
      glycoprotein (P-gp), multidrug resistance-associated protein 1 (MRP1), and lung
      resistance-related protein (LRP). Tumor necrosis factor (TNF-alpha) is able to
      modify the expression of these three proteins in different cell types. The effect
      of TNF-alpha in the clinical situation on patients with soft tissue sarcomas
      (STS) is indeterminate. METHODS: Thirty-seven patients with a locally advanced
      extremity STS underwent hyperthermic isolated limb perfusion (HILP) with TNF
      alpha and melphalan; 15 patients received additional interferon gamma. Clinical
      and histologic responses were documented and used to define the overall response.
      Samples before and after HILP were analyzed immunohistochemically for P-gp, MRP1,
      and LRP. Samples were scored as negative or positive (< or = 5% or > 5% positive
      tumor cells). RESULTS: Six patients had an overall complete response, 25 patients
      had a partial response, and 4 patients with STS revealed no change; in 2
      patients, the response remained unclear. The percentage STS samples that were
      positive for all three proteins dropped from 92% before HILP to 85% after HILP. P
      gp positive samples were encountered more often than MRP1 positive samples (P <
      0.05). The percentage of samples that were negative for all three MDR proteins
      increased after HILP from 6% to 16%. MDR status had no significant correlation
      with tumor response. CONCLUSIONS: HILP with TNF-alpha and melphalan results in
      excellent overall tumor response in patients with locally advanced STS. STS more
      often are positive for P-gp than for MRP1. MDR status in patients with STS is not
      predictive for tumor response after HILP. Data from the current study suggest
      that the combination of TNF-alpha and melphalan does not induce MDR positive STS:
      a result with clinical importance when consecutive, adjuvant, doxorubicin
      containing chemotherapy is considered.

PMID- 11346878
TI  - The association between treatment-specific optimism and depressive symptomatology
      in patients enrolled in a Phase I cancer clinical trial.
AB  - BACKGROUND: Previous research has found that cancer patients often overestimate
      the likelihood that they will achieve a positive response in Phase I trials.
      However, maintaining optimistic expectations may help patients cope with a poor
      prognosis and uncertain outcome. The authors prospectively examined the
      association between treatment-specific optimism and mental health among patients
      participating in a Phase I/b trial. METHODS: Twenty-four patients with metastatic
      renal cell carcinoma and 22 patients with metastatic melanoma completed an
      assessment battery at the beginning of treatment and 3 weeks later, on the final
      day of treatment. Patients completed measures of treatment-specific optimism
      (e.g., beliefs regarding the treatment working), depressive symptomatology, mood
      disturbance, and overall distress. RESULTS: The majority of patients believed
      that the treatment would either cure them (87%) or stop cancer progression (85%).
      Regression analyses revealed that the level of treatment-specific optimism (e.g.,
      "The treatment I am receiving may cure me") was associated negatively with
      baseline measures of depressive symptoms (P < 0.006), mood disturbance (P <
      0.001), and symptoms of distress (P < 0.0001) after controlling for age, number
      of metastases, and time since diagnosis. Patients with symptoms of clinical
      depression at baseline reported significantly lower levels of treatment-specific
      optimism than patients without symptoms (P < 0.03). Treatment-specific optimism
      also was associated negatively with symptoms of depression at the end of
      treatment (P < 0.003), controlling for symptoms of depression at the beginning of
      treatment. CONCLUSIONS: The results of the current study suggest that high levels
      of treatment-specific optimism are associated with better mental health outcomes
      at both the beginning and end of treatment.

PMID- 11346880
TI  - Retinoic acid-induced expression of autotaxin in N-myc-amplified neuroblastoma
      cells.
AB  - Neuroblastoma, the most common extracranial solid tumor in children, arises from
      precursors of the sympathetic nervous system. Neuroblastoma cell lines are
      responsive to the differentiation agent retinoic acid, which induces its effects
      by altering transcription rates of specific target genes. We identified autotaxin
      (ATX), which encodes an autocrine tumor motility-stimulating factor, as a gene
      whose expression is significantly induced by retinoic acid in neuroblastoma
      cells. ATX induction was specific for neuroblastoma cell lines that contain N-myc
      amplification, a cytogenetic feature commonly associated with aggressive
      neuroblastomas. Although ATX expression was associated with amplification of the
      N-myc locus, N-myc itself was neither sufficient nor required for ATX expression,
      suggesting that a coamplified gene is responsible. ATX induction by retinoic acid
      was due to increased transcription and required new protein synthesis.

PMID- 11346881
TI  - Comparative analysis of ras proto-oncogene mutations in selected mammalian
      tumors.
AB  - Point mutations within ras proto-oncogenes are frequently detected in human
      malignancies and in different types of experimentally induced tumors in animals.
      In contrast to findings in experimental animal models of carcinogenesis, little
      is known about the incidence of ras mutations in naturally occurring animal
      tumors. In the present study, we investigated whether point mutations,
      particularly within the mutational hot-spot codons 12, 13, and 61, occur at
      comparable frequencies in human malignancies and spontaneously occurring tumors
      in other mammalian species. Two hundred seventy-nine of the most frequent canine
      and feline neoplasms were analyzed for changes in mutational hot-spot regions of
      the N-, Ki-, and Ha-ras genes. DNA fragments from exons 1 and 2 of all three ras
      genes were amplified by polymerase chain reaction, and the presence of point
      mutations was assessed by single-strand conformation polymorphism analysis and
      direct sequencing of amplified products. Only one sample, a case of canine
      melanoma, exhibited an Ha-ras mutation. Thus, our data strongly suggested that
      ras mutations at the hot-spot loci are apparently very rare and do not play a
      major role in the pathogenesis of the spontaneously occurring canine and feline
      tumors investigated. These observations were in marked contrast to those in
      experimental rodent models of carcinogen-induced mammary and skin tumors that
      described a consistent association with Ha- or Ki-ras activation. The role of ras
      oncogene activation in related human malignancies therefore cannot be readily
      inferred from studies of experimental carcinogenesis in animal models.

PMID- 11346882
TI  - 2,4,4'-trichlorobiphenyl increases STAT5 transcriptional activity.
AB  - The promoting effects of polychlorinated biphenyls (PCBs) have been studied
      extensively in a variety of two-stage carcinogenesis models. However, the
      molecular mechanisms responsible for the promotion effects of PCBs have not been
      elucidated. We measured the effect of PCBs on DNA-binding proteins involved in
      cell proliferation and transformation. Male Sprague-Dawley rats were injected
      intraperitoneally with mono-, di-, tri-, tetra-, or hexachlorobiphenyls (300
      micromol/kg/d) each day for 4 d and killed 4 h after the last injection. To
      detect alterations in nuclear proteins that could explain the tumor-promoter
      activity of PCBs, liver nuclear extracts were analyzed by electrophoretic
      mobility shift assays. Electrophoretic mobility shift assay analysis of signal
      transducers and activators of transcription (STAT)-binding activity to a
      consensus gamma-interferon-activated sequence (GAS) element was compared in liver
      nuclear extracts from treated rats. STAT-binding activity was eightfold to
      tenfold higher in nuclear extracts from animals treated with 2,4,4'-trichloro-
      (PCB 28) and 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153). Analysis of the protein
      complex binding to the GAS element, with antibodies specific for STAT3, STAT5,
      and STAT6, indicated that the protein complex was made up of STAT5 and STAT6
      proteins. HepG2 cells transiently transfected with a luciferase reporter gene
      construct containing many STAT5 binding sites were treated with PCB 28 and PCB
      153. PCB 28 stimulated a greater than 25-fold increase in luciferase activity at
      the highest concentration tested, 1.0 microg/mL. However, enhanced luciferase
      activity did not occur with PCB 153 treatment. 4-Chlorobiphenyl (PCB 3), PCB 28,
      and PCB 153 treatment of Sprague-Dawley rats resulted in a large increase in
      protein binding to a consensus activated protein-1 (AP-1) element. However, 3,4
      dichlorobiphenyl (PCB 12) and 3,3',4,4'-tetrachlorobiphenyl (PCB 77) treatments
      did not increase AP-1 transcription activity. Further analysis of the proteins
      binding to the AP-1 consensus sequence with antibodies specific for c-fos, junD,
      and junB indicated that the protein composition consists of junD proteins. These
      data showed functional differences between noncoplanar and coplanar PCBs with
      respect to STAT activation and AP-1-DNA binding.

PMID- 11346883
TI  - Hydrogen peroxide promotes transformation of rat liver non-neoplastic epithelial
      cells through activation of epidermal growth factor receptor.
AB  - Previous studies demonstrated that hydrogen peroxide (H(2)O(2)) is a tumor
      promoter in the rat liver epithelial cell line T51B. We investigated the pathway
      linking H(2)O(2) to tumor promotion. H(2)O(2) can directly induce tyrosine
      phosphorylation of epidermal growth factor receptor (EGFR). H(2)O(2) and
      epidermal growth factor exerted similar effects on the induction of early growth
      response genes, disruption of gap junction communication, triggering of calcium
      inflow, and promotion of transformation. Furthermore, the effect of H(2)O(2) on
      tumor promotion was blocked by abrogation of EGFR activation. Our results
      suggested that tumor promotion by H(2)O(2) is mediated mainly through activation
      of EGFR in T51B cells.

PMID- 11346884
TI  - Role of intracellular interleukin-1 receptor antagonist in skin carcinogenesis.
AB  - Interleukin 1 (IL-1) is a major mediator of inflammation and exerts pleiotropic
      effects on many systems. To elucidate the role of its endogenous inhibitor,
      intracellular IL-1 receptor antagonist (icIL-1Ra), in mouse skin, we produced an
      icIL-1Ra-overexpressing skin carcinoma cell line (icIL-1Ra-JWF2). Altered
      expression of icIL-1Ra did not change IL-1alpha mRNA levels in these transfected
      cells. In icIL-1Ra-JWF2 cells, however, cyclooxygenase-2 mRNA levels were
      dramatically reduced and shown to be transcriptionally regulated by icIL-1Ra. To
      determine the effect of icIL-1Ra on cell proliferation, cell counts were done 24
      h after plating equal numbers of cells. Cells from three icIL-1Ra-JWF2 clones
      showed significantly reduced growth rates compared with parental JWF2 cells. We
      subcutaneously injected five independent clones of icIL-1Ra-JWF2 cells into nude
      mice and measured the tumor doubling time by weekly measurements of tumor volume.
      IcIL-1Ra appeared to significantly slow the growth of tumors in vivo.
      Collectively these observations suggest that IL-1Ra has antiproliferative effects
      in murine skin carcinoma cells.

PMID- 11346885
TI  - Inhibitory effect of silibinin on ligand binding to erbB1 and associated
      mitogenic signaling, growth, and DNA synthesis in advanced human prostate
      carcinoma cells.
AB  - We recently showed the inhibitory effect of a flavonoid antioxidant, silymarin,
      on erbB1-Shc activation in prostate cancer (PCA) DU145 cells. In the present
      study, we performed more detailed mechanistic and molecular modeling studies with
      pure silibinin to assess and define its effect on membrane signaling related to
      erbB1 activation in human PCA LNCaP and DU145 cells. Studies also were performed
      to establish the biologic responses toward extracellular signal-regulated protein
      kinase 1/2 (ERK1/2) activation, cell growth, and DNA synthesis. Treatment of
      serum-starved cells with various doses of silibinin for 2 h followed by (125)I
      epidermal growth factor (EGF) showed 30-75% inhibition in ligand binding and 55
      95% inhibition in its internalization in LNCaP cells and 20-64% and 12-27%
      inhibition in these two events in DU145 cells. Time-response studies showed
      similar effects. In further studies, treatment of serum-starved cultures with
      silibinin followed by EGF showed strong inhibitory effects on membrane and
      cytoplasmic signaling molecules. In the case of erbB1 activation, silibinin
      showed a 58-75% decrease in LNCaP and a 40-100% decrease in DU145 cells at 50,
      75, and 100-microg/mL doses. Inhibitory effects of silibinin also were evident on
      ERK1/2 activation (20-80% inhibition) in both cell lines. Treatment of serum
      starved cultures with silibinin resulted in 20-40% and 30-55% inhibition of LNCaP
      and DU145 cell growth, respectively, at similar doses after 1-3 d of treatment,
      and 10-50% cell death in both cell lines. Under 10% serum conditions, identical
      silibinin treatments resulted in 20-65% inhibition of cell growth in LNCaP and
      DU145 cells but did not cause any cell death. Similar doses of silibinin
      treatments for 24 h also resulted in 25-60%, 35-40%, and 36-50% inhibition of DNA
      synthesis when cells were cultured in 10% serum, totally serum starved, and serum
      starved plus stimulated with EGF, respectively. Molecular modeling of silibinin
      showed that it is a highly lipophilic compound, suggesting that it interacts with
      lipid-rich plasma membrane, including binding with erbB1, thereby competing with
      the EGF-erbB1 interaction. Because the ligand-erbB1 autocrine-loop is causally
      involved in advanced and androgen-independent PCA, the observed effects of
      silibinin and its strong lipophilic nature could be useful in developing this
      agent for the prevention and therapy of PCA.

PMID- 11346886
TI  - Sensorimotor mapping of the human cerebellum: fMRI evidence of somatotopic
      organization.
AB  - Functional magnetic resonance imaging (fMRI) was employed to determine areas of
      activation in the cerebellar cortex in 46 human subjects during a series of motor
      tasks. To reduce the variance due to differences in individual anatomy, a
      specific transformational procedure for the cerebellum was introduced. The
      activation areas for movements of lips, tongue, hands, and feet were determined
      and found to be sharply confined to lobules and sublobules and their sagittal
      zones in the rostral and caudal spino-cerebellar cortex. There was a clear
      symmetry mirroring at the midline. The activation mapped as two distinct
      homunculoid representations. One, a more extended representation, was located
      upside down in the superior cerebellum, and a second one, doubled and smaller, in
      the inferior cerebellum. The two representations were remarkably similar to those
      proposed by Snider and Eldred [1951] five decades ago. In the upper
      representation, an intralimb somatotopy for the right elbow, wrist, and fingers
      was revealed. The maps seem to confirm earlier electrophysiological findings of
      sagittal zones in animals. They differ, however, from micromapping reports on
      fractured somatotopic maps in the cerebellar cortex of mammals. We assume that
      the representations that we observed are not solely the result of spatial
      integration of hemodynamic events underlying the fMRI method and may reflect
      integration of afferent peripheral and central information in the cerebellar
      cortex.

PMID- 11346887
TI  - Analysis and use of FMRI response delays.
AB  - In this study, we implemented a new method for measuring the temporal delay of
      functional magnetic resonance imaging (fMRI) responses and then estimated the
      statistical distribution of response delays evoked by visual stimuli (checkered
      annuli) within and across voxels in human visual cortex. We assessed delay
      variability among different cortical sites and between parenchyma and blood
      vessels. Overall, 81% of all responsive voxels showed activation in phase with
      the stimulus while the remaining voxels showed antiphase, suppressive responses.
      Mean delays for activated and suppressed voxels were not significantly different
      (P < 0.001). Cortical flat maps showed that the pattern of activated and
      suppressed voxels was dynamically induced and depended on stimulus size. Mean
      delays for blood vessels were 0.7-2.4 sec longer than for parenchyma (P < 0.01).
      However, both parenchyma and blood vessels produced responses with long delays.
      We developed a model to identify and quantify different components contributing
      to variability in the empirical delay measurements. Within-voxel changes in delay
      over time were fully accounted for by the effects of empirically measured fMRI
      noise with virtually no measurable variability associated with the stimulus
      induced response itself. Across voxels, as much as 47% of the delay variance was
      also the result of fMRI noise, with the remaining variance reflecting fixed
      differences in response delay among brain sites. In all cases, the contribution
      of fMRI noise to the delay variance depended on the noise power at the stimulus
      frequency. White noise models significantly underestimated the fMRI noise
      effects.

PMID- 11346888
TI  - Control of semantic interference in episodic memory retrieval is associated with
      an anterior cingulate-prefrontal activation pattern.
AB  - Prefrontal activation is a consistent finding in functional neuroimaging studies
      of episodic memory retrieval. In the present study we aimed at a further analysis
      of prefrontal neural systems involved in the executive control of context
      specific properties in episodic memory retrieval using an event-related fMRI
      design. Nine subjects were asked to learn two 20-item word lists that consisted
      of concrete nouns assigned to four semantic categories. Ten items of both word
      lists referred to the same semantic category. Subjects were instructed to
      determine whether nouns displayed in random order corresponded to the first 20
      item target list. The interference evoked by the retrieval of semantically
      related items of the second list resulted in significantly longer reaction times
      compared to the noninterference condition. Contrasting the interference against
      the noninterference retrieval condition demonstrated an activation pattern that
      comprised a right anterior cingulate and frontal opercular area and a left
      lateralized dorsolateral prefrontal region. Trial averaged time series revealed
      that the PFC areas were selectively activated at the interference condition and
      did not respond to the familiarity of learned words. These findings suggest a
      functionally separable role of prefrontal cortical areas mediating processes
      associated with the executive control of interfering context information in
      episodic memory retrieval.

PMID- 11346889
TI  - Comparative electrophysiological and hemodynamic measures of neural activation
      during memory-retrieval.
AB  - The spatial and temporal characteristics of the brain processes underlying memory
      retrieval were studied with both event-related potentials (ERP) and positron
      emission tomography (PET) techniques. Subjects studied lists of 20 words and then
      performed episodic (old/new judgment) or semantic (living/nonliving decision)
      retrieval tasks on multiple four-item test lists, each lasting 10 sec. The PET
      and ERP measurements at test were assessed in relation to both the task (episodic
      vs. semantic) and the item (old vs. new or living vs. nonliving). Episodic
      retrieval was associated with increased blood flow in the right frontal lobe
      (Brodmann Area 10) and a sustained, slowly developing positive ERP shift recorded
      from the right frontopolar scalp. Semantic retrieval was associated with
      increased blood flow in the left frontal (Area 45) and temporal (Area 21) lobes
      but no clear ERP concomitant. The two retrieval tasks also differed from each
      other in the ERPs to single items in an early (300-500 ms) time window. Item
      related comparisons yielded convergent results mainly if the retrieved
      information was relevant to the given task (e.g., old/new items during episodic
      retrieval and living/nonliving items during semantic retrieval). Episodically
      retrieved old items were associated with increased blood flow in the left medial
      temporal lobe and a transient increase in the amplitude of the late positive
      component (500-700 ms) of the ERP. Semantically retrieved living items were
      associated with increased blood flow in the left frontal cortex and anterior
      cingulate and a transient late frontal slow wave (700-1,500 ms) in the ERPs.
      These results indicate that the brain regions engaged in memory retrieval are
      active in either a sustained or transient manner. They map task-related processes
      to sustained and item-related processes to transient neural activity. But they
      also suggest that task-related factors can transiently affect early stages of
      item processing.

PMID- 11346891
TI  - Induction of cardiac fibrosis by angiotensin II.
AB  - The possible contributions of the angiotensin receptor subtypes 1 (AT1) and 2
      (AT2) to angiotensin II-induced changes in collagen secretion and production were
      studied using the specific angiotensin receptor AT1 and AT2 antagonists
      telmisartan and P-186. The role of the renin-angiotensin system and its
      interaction with transforming growth factor-beta 1 (TGF-beta 1) in collagen
      deposition in cardiac fibroblasts in relation to the development of myocardial
      fibrosis is also discussed. Cardiac fibroblasts (from normal male adult rats)
      from passage 2 were cultured to confluency and incubated in the presence of
      angiotensin II (ANG II) in a concentration range of 10(-10)-10(-6) M in serum
      free Dulbecco's MEM medium for 24 h. Collagen production and secretion were
      assayed by [3H]-proline incorporation and noncollagen production and secretion
      were also analyzed. ANG II dose-dependently increased collagen secretion and
      production in rat adult cardiac fibroblasts in culture. Noncollagen secretion and
      production were also concentration-dependently increased by ANG II. Addition of
      100 nmol/l ANG II increased (p < 0.01) collagen secretion and production by 75 +/
      6 (SEM) and 113 +/- 23%, respectively, and noncollagen secretion and production
      by 65 +/- 6 and 57 +/- 16%, respectively. Pretreatment of cardiac fibroblasts
      with telmisartan completely blocked the ANG II-induced increase in collagen
      secretion (p < 0.001) and production (p < 0.05) and in noncollagen secretion (p <
      0.01) and production (p < 0.01). P-186 had no effect on the ANG II-induced
      increase in collagen secretion and production. Addition of telmisartan and P-186
      did not affect collagen secretion and production in basal cardiac fibroblasts.
      TGF-beta 1 also concentration- and time-dependently increased the secretion and
      production of collagen in cardiac fibroblasts. Our data demonstrate that the
      effects of ANG II on collagen secretion and production in adult rat cardiac
      fibroblasts in culture are AT1-receptor mediated since they were abolished by the
      specific AT1-receptor antagonist telmisartan but not by the specific AT2-receptor
      antagonist P-186. The ability of ANG II to induce collagen synthesis in cardiac
      fibroblasts may be mediated by increased TGF-beta 1 production.

PMID- 11346892
TI  - Evidence that Toki-shakuyaku-san and its ingredients enhance the secretion of a
      cytokine-induced neutrophil chemoattractant (CINC/gro) in the ovulatory process.
AB  - We investigated the effects of Toki-shakuyaku-san and its crude ingredients in
      relation to the secretion of a cytokine-induced neutrophil chemoattractant,
      CINC/gro, interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF
      alpha) in the ovulatory process. Toki-shakuyaku-san significantly (p < 0.01)
      stimulated the secretion of 17 beta-estradiol but did not stimulate the secretion
      of progesterone in cultured whole ovarian dispersates. Toki-shakuyaku-san
      enhanced the secretion of CINC/gro in a dose-dependent manner and the production
      of CINC/gro at concentrations of 10 and 100 micrograms/ml of Toki-shakuyaku-san
      increased significantly (p < 0.01). Toki-shakuyaku-san also enhanced secretions
      of both IL-1 beta and TNF alpha, which are known to stimulate the secretion of
      CINC/gro in the ovulatory process. The production of TNF alpha increased
      significantly (p < 0.05) with 10 and 100 micrograms/ml of Toki-shakuyaku-san.
      Atractylodis Lanceae Rhizoma, Cnidii Rhizoma, Angelicae Radix, Paeoniae Radix and
      Alismatis Rhizoma, which are crude ingredients of Toki-shakuyaku-san,
      significantly (p < 0.01) enhanced the secretion of CINC/gro at concentrations of
      100 micrograms/ml. The results of this study show that Toki-shakuyaku-san can
      stimulate the secretion of 17 beta-estradiol and stimulate the ovulatory process
      by stimulating the production of CINC/gro, IL-1 beta and TNF alpha in vitro. As a
      treatment for ovulatory disorders, Toki-shakuyaku-san may have stimulatory
      effects on both steroidogenesis and the ovulatory process.

PMID- 11346893
TI  - Anticonvulsant effect of nimodipine alone and in combination with diazepam and
      phenytoin in a mouse model of status epilepticus.
AB  - The effect of nimodipine alone and in combination with diazepam or phenytoin was
      tested in the electroshock-induced mouse model of status epilepticus. Status
      epilepticus was induced by transauricular electrical stimulation with a stimulus
      of 15 mA at 0.5, 3, 10, 20 and 30 min, starting half an hour after
      intraperitoneal administration of vehicle/drug. The median effective doses of
      diazepam and phenytoin alone and in combination with a fixed dose of nimodipine
      (24 mg/kg) was calculated. The ED50s of diazepam and phenytoin were found to be
      10.5 and 9 mg/kg, respectively. When nimodipine was combined with diazepam or
      phenytoin, the ED50 values decreased to 3.77 mg/kg and 7.15 mg/kg, respectively.
      The severity of seizures was also decreased by combination with nimodipine as
      compared to diazepam and phenytoin given alone. To study the effect of nimodipine
      on psychomotor impairments produced by diazepam and phenytoin three tests were
      performed: rotarod, behavioral despair and hole board. Nimodipine did not show
      protective effects on its own but potentiated the anticonvulsant effects of
      diazepam and phenytoin. Furthermore, the combination of nimodipine with diazepam
      and phenytoin produced lesser impairment of psychomotor functions.

PMID- 11346894
TI  - Effect of different doses of S-adenosyl-L-methionine on paracetamol
      hepatotoxicity in a mouse model.
AB  - This study investigated the hepatoprotective effects of N-acetylcysteine and
      different doses of S-adenosyl-L-methionine after a single intraperitoneal
      overdose of paracetamol in mice. Plasma concentrations of paracetamol metabolites
      were also determined. Female mice (Souris OFl strain) 16 weeks old and weighing
      30 g were fasted for 18 h prior to intraperitoneal (i.p.) administration of 375
      mg/kg (2.5 mmol/kg) of paracetamol. Experimental subgroups included mice
      administered paracetamol only (control group), those given of N-acetylcysteine 1
      g/kg (6.13 mmol/kg) i.p. immediately after paracetamol overdose (T0) and 6 h
      after dosing (T6) and those administered S-adenosyl-L-methionine at doses of 20
      mg/kg (0.05 mmol/kg) and 1 g/kg (2.5 mmol/kg) i.p. at T0 and T6. Twenty-four
      hours after paracetamol overdose, mortality and liver necrosis were significantly
      lower (p < 0.01) in mice treated with 2.5 mmol/kg of S-adenosyl-L-methionine and
      N-acetylcysteine at T0 as compared with the remaining subgroups. Plasma ALT
      concentrations were significantly lower (p < 0.01) in mice treated with 2.5
      mmol/kg of S-adenosyl-L-methionine than in those given N-acetylcysteine. Plasma
      concentrations of paracetamol metabolites showed an increase in the glucuronide
      conjugate and a decrease in the mercapturic acid conjugate in N-acetylcysteine
      treated mice and an overall decrease in the conjugation pathway without changes
      in the oxidative pathway in S-adenosyl-L-methionine-treated animals. We conclude
      that S-adenosyl-L-methionine at doses of 1 g/kg (2.5 mmol/kg) i.p. was equally
      effective as 1 g/kg (6.13 mmol/kg) N-acetylcysteine for preventing hepatotoxicity
      after paracetamol overdose in mice. S-adenosyl-L-methionine may be a therapeutic
      alternative to N-acetylcysteine as an antidote for poisoning with paracetamol.

PMID- 11346895
TI  - Effects of nifedipine, verapamil, diltiazem and trifluoperazine on the
      antinociceptive activity of acetaminophen.
AB  - The influence of the calcium channel blockers (CCBs) nifedipine, verapamil and
      diltiazem, and the calmodulin antagonist trifluoperazine on the antinociceptive
      activity of acetaminophen was studied in male albino mice. The nociceptive
      response was determined by the acetic acid writhing test. Nifedipine (50 or 20
      mg/kg), verapamil (20 mg/kg), diltiazem (70 mg/kg) and trifluoperazine (3 mg/kg)
      were administered orally alone or 1 h before acetaminophen (100 mg/kg).
      Nifedipine (50 mg/kg), verapamil, diltiazem and trifluoperazine administered
      alone demonstrated significant antinociceptive effects compared to controls.
      Nifedipine, verapamil, diltiazem and trifluoperazine applied 1 h before
      acetaminophen potentiated its antinociceptive activity, which was strongest in
      mice injected with verapamil and nifedipine (20 mg/kg). It was established that 1
      h after nifedipine (50 mg/kg) treatment, cytochrome P450 content, NADPH
      cytochrome c reductase and ethylmorphine-N-demethylase (EMND) activities were
      increased in the liver microsomes. Verapamil, diltiazem and trifluoperazine did
      not change the drug metabolizing enzymes studied. It is assumed that their effect
      on acetaminophen analgesia is not associated with the changes in acetaminophen
      oxidative metabolism in the liver.

PMID- 11346896
TI  - Differential role of dopamine D1 and D2 receptors in isoniazid-induced vacuous
      chewing movements.
AB  - Tardive dyskinesia (TD) is a syndrome of potentially irreversible and involuntary
      hyperkinetic disorders that occurs during chronic neuroleptic therapy and is a
      major limitation of such therapy. Vacuous chewing movements (VCMs) in rats have
      been widely accepted as an animal model of tardive dyskinesia. In the present
      study isoniazid (1, 2 and 5 microM i.c.v.) dose-dependently produced VCMs in
      rats. The response produced by a 10-microM dose was lower than that of earlier
      doses but was statistically significant when compared to a saline-treated group.
      Diazepam (1 and 4 mg/kg i.p.) and progabide (50 and 100 mg/kg i.p.) dose
      dependently reversed the isoniazid-induced VCMs. Haloperidol (0.5 and 1 mg/kg
      i.p.) and SCH-23390 (0.25 and 0.5 mg/kg i.p.) reversed the isoniazid-induced VCMs
      in a dose-dependent manner. Sulpiride (25 and 50 mg/kg i.p.), a dopamine D2
      receptor antagonist, had no effect on isoniazid-induced VCMs. SKF-38393 (10 and
      15 mg/kg i.p.) dose-dependently augmented the isoniazid-induced VCMs. Quinpirole
      0.02 mg/kg i.p. had no effect on isoniazid-induced VCMs but a higher quinpirole
      dose (0.05 mg/kg) significantly reduced isoniazid-induced VCMs. Isoniazid (2
      microM i.c.v.) produced stereotypy (grooming and rearing) in rats. Haloperidol
      (0.5 and 1 mg/kg i.p.), SCH-23390 (0.25 and 0.5 mg/kg i.p.) and sulpiride (25 and
      50 mg/kg i.p.) decreased the severity of isoniazid-induced stereotypy. SKF-38393
      (10 and 15 mg/kg i.p.) dose-dependently augmented the isoniazid-induced grooming
      behavior more prominently as compared to quinpirole (0.02 and 0.05 mg/kg i.p.);
      on the other hand quinpirole potentiated isoniazid-induced rearing behavior. In
      conclusion, the results of the present study demonstrated the differential
      involvement of dopamine D1 and D2 receptors in isoniazid-induced VCMs.

PMID- 11346898
TI  - A review of the isolated kidney as an experimental model for pharmacokinetic
      studies.
AB  - Traditional distribution studies have been based on methods affording steady
      state partition coefficient or sparsely defined tissue profiles. Isolation organ
      techniques provide a methodology for complete description of drug disposition at
      any particular tissue; the kidney constitutes a case for importance for those
      drugs eliminated by renal excretion of those whose toxicological or
      pharmacological target space is located at this level. The aim of the present
      review is to analyze the use of the isolated perfused kidney in pharmacokinetic
      studies and its potential in this field.

PMID- 11346897
TI  - Circadian distribution of oral opioid consumption in cancer patients.
AB  - Diurnal variations are reported in pain perception, potency of placebo and in the
      pharmacokinetics of morphine. It is not established if such diurnal variation
      should be reflected in the routine prescription of analgesic drugs to cancer
      patients. One approach for investigating this question is to study the circadian
      rhythm of patients' requests for analgesics. We included 40 patients with
      malignant disease and intolerable pain despite treatment with weak opioids. Weak
      opioids were stopped and the patients' pain treatment was restricted for the next
      2 days to strong oral opioids (ketobemidone) given on an as-needed basis. The
      number and times of all ketobemidone administrations were recorded. No
      significant diurnal variation in use of ketobemidone was observed. A descriptive
      curve that interpolates between successive observations displayed only slight
      circadian fluctuations of opioid consumption. Thus, the data reported in this
      paper does not support the necessity of considering chronopharmacological factors
      in the routine prescription of oral opioids.

PMID- 11346899
TI  - [Role of computed tomography in pulmonary aspergillosis. 20 cases].
AB  - OBJECTIVE: Aspergilloma is the most common form of pulmonary aspergillosis. The
      purpose of this work was to compare computed tomographic findings with features
      observed on standard radiographs. PATIENTS AND METHODS: We retrospectively
      reviewed 20 cases of pulmonary aspergilloma. These patients (mean age 36 years)
      were followed after cure of pulmonary tuberculosis and consulted for hemoptysis.
      All underwent computed tomography (CT) and standard radiographic explorations.
      Serology was positive for Aspergillus in 16 cases and clinical and radiographic
      findings led to the diagnosis in the 4 others. Both supine and prone positions
      were used for thoracic CT. Slice thickness was 5 mm without contrast injection.
      RESULTS: In many cases, standard films evidenced the typical mycetoma seen as a
      rounded mass of soft tissue density filling a portion of a preexisting cavity or
      as an air crescent sign, but atypical alveolar opacities, aeric images without
      aspergillosis colonization and parenchymal destruction predominated in certain
      cases. The CT-scan demonstrated these features even better revealing the typical
      cavity in 80% of the cases or an air crescent in 20%. Mobility of the fungus ball
      was demonstrated by comparison of the prone and supine images. The characteristic
      CT features allowed certain diagnosis of aspergilloma in 6 patients with atypical
      radiographic or serologic results. DISCUSSION: Computed tomography is highly
      contributive to the diagnosis of pulmonary aspergillosis, particularly in case of
      small cavities that may be missed on the standard films. Recognition of the
      mobility of the fungal ball enables differentiation from a tumor or infectious
      lesion. CT is also helpful for guiding transparietal treatment. CONCLUSION: A
      computed tomography series should be obtained in former tuberculosis patients
      consulting for hemoptisis.

PMID- 11346900
TI  - [Management of self poisoning at an emergency medical center].
AB  - OBJECTIVE: We examined the response given to calls for acute self-poisonings in a
      French department (Vienne) in order to determine current management practices.
      PATIENTS AND METHODS: We reviewed retrospectively all calls to the Vienne pre
      hospital emergency care center between January 1997 and December 1999 that
      concerned acute self-poisoning. There were 2,057 calls for 1,312 women and 708
      men (mean age 35.3 +/- 13.7 years, age range 8-99 years). RESULTS: The call was
      made by a private person in 72.1% of the cases, by a physician in 14.4% and by a
      first-aid worker in 8.4%. The annual incidence was 1.83 calls per 1000
      inhabitants. Self-poisoning led to death in 1% of the cases (mean age 40.8 +/-
      10.8 years, age range 27-70 years). A total of 3,225 toxic agents were
      identified, i.e. 1.56 +/- 1 agent per poisoning (range 1-10). Psychotrops
      predominated and were found in 74.8% of the suicide attempts with drugs. Non-drug
      poisonings accounted for 2.5% of the cases. The emergency center responded to the
      call by dispatching an ambulance (56.4%) or a medicalized emergency care unit
      (22.4%), providing counsel (18.2%), or calling in a physician (1.1%). A mobile
      hospital unit was dispatched in 58% of the cases judged to involve a life
      threatening situation. CONCLUSION: Self-poisoning is one of the most common
      situations managed by pre-hospital emergency care centers. The response given to
      emergency calls would appear to be insufficiently medicalized.

PMID- 11346901
TI  - [Isolation of Vibrio strains in French coastal waters and infection with Vibrio
      cholerae non-O1/non-O139].
AB  - OBJECTIVE: Although the incidence in France of V. cholerae non-O1/non-O139
      infection in man has increased since 1996, it remains low (7 cases in 1999).
      After the death in 1994 of an immunodepressed patient presenting a skin lesion
      showing superinfection by a strain of non-O1/non-O139 V. cholerae following
      exposure to seawater, we examined 22 samples of sea-water collected from 20
      French coastal areas (Mediterranean coast). METHODS: The sea-water samples were
      filtered and enriched with alkaline peptone water (APW), and the strains of
      Vibrio were isolated on TCBS, SS and BCP media and identified using the API 20 E
      system (bioMerieux, France). RESULTS: We isolated 6 strains belonging to 3
      species of Vibrio: 2 V. cholerae (non-O1/non-O139), 3 V. parahaemolyticus and 1
      V. alginolyticus. One of the V. cholerae strains was isolated from sea-water
      sampled at the coastal town in which the patient had been staying. The seawater
      strains exhibited high sensitivity (MIC determined by agar dilution) to the
      following antibiotics: aminoglycosides, tetracyclines, azithromycin,
      cotrimoxazole, rifampicin and fluoroquinolones. The beta-lactams were very active
      against strains of V. cholerae isolated from seawater, while the strain isolated
      from this patient presented a new carbenicillinase (CARB-6) recently described.
      CONCLUSION: The presence of Vibrio in seawater along the French coast-line
      constitutes a risk for immunocompromised patients, and the severity of Vibrio
      infections warrants improved monitoring both of these organisms and of the marine
      environment. In addition, awareness on the part of doctors would allow patients
      at risk to be warned against these dangers.

PMID- 11346902
TI  - [Fulminant hepatocellular necrosis following administration of docetaxel].

PMID- 11346903
TI  - [Gastric metastasis from breast cancer].

PMID- 11346904
TI  - [Low-molecular-weight heparin prophylaxis during pregnancy: a retrospective study
      in 119 women].

PMID- 11346905
TI  - [The reality of disease: the testimony of Arthur and Isabelle Rimbaud].

PMID- 11346906
TI  - [Geriatrics and rehabiliation: role of the hospital in healthcare networks?].
AB  - OBJECTIVE: There is no accepted definition of geriatric post-acute or
      rehabilitation care. The exact role within the healthcare network and the
      function of units providing such care remain to be clarified. We describe the
      activity of geriatric post-acute or rehabilitation care units in four French
      hospitals to identify common features and provide elements of practical interest
      concerning their role in the healthcare network. METHODS: Data from 4 healthcare
      institutions in France recorded in the 1999 Medical Information System were
      analyzed. RESULTS: Geriatric post-acute or rehabilitation units generally
      provided care for patients over 80 years of age in short-stay wards. These
      patients were dependent and recovering from an acute illness. In addition to
      rehabilitation and medical care, given according to the patients' needs, the
      units also provided social counseling and acute care as in other short-stay
      wards. A wide variety of pathological conditions was observed. At discharge most
      patients returned to their home or were transferred to a nursing home.
      CONCLUSION: Geriatric post-acute or rehabilitation units meet the requirements
      proposed in French legislation and in addition provide social counseling and
      acute care services, which is evidence of the deficiencies in the healthcare
      network in the field of elderly patient care.

PMID- 11346907
TI  - [The secret passage].

PMID- 11346908
TI  - [Postoperative cognitive disorders in the elderly].
AB  - TWO DISTINCT CATEGORIES: Postoperative cognitive disorders include delirium and
      long-term cognitive dysfunction. DELERIUM: Delirium is an acute state occurring
      early during the postoperative period. It may be considered as an acute cerebral
      insufficiency which may be consecutive both to the negative effects of aging and
      chronic illness on cognitive function, and to the cerebral impact of operative
      stress. In addition, precipitating postoperative medical factors may facilitate
      cerebral failure. Only a few studies have been devoted to prevention programs
      aimed at reducing the risk of postoperative delirium. Nevertheless, we can
      hypothesize that a preoperative gerontology assessment would be effective in
      determining risk factors of delirium in old patients and thus enable proposing
      individual postoperative management. LONG-TERM COGNITIVE DYSFUNCTION: The
      definition of this clinical picture is less precise than delirium. Long-term
      cognitive dysfunction corresponds to a loss of cognitive performance in the weeks
      and months after anesthesia. The IPOCD1 study conducted in a large cohort of
      elderly patients has shown that postoperative cognitive dysfunction was present
      in 25.8% of patients 1 week after surgery and in 9.9% 3 months after surgery. One
      to two years after surgery, cognitive dysfunction was observed in 10.4% of
      patients compared with 10.6% in a control population of non-operated patients. We
      would suggest that in many cases, postoperative cognitive dysfunction may result
      from preoperative dementia unmasked by surgery.

PMID- 11346909
TI  - [Hypovitaminosis D: a major worldwide public health problem].
AB  - PHYSIOLOGY: Vitamin D increases intestinal absorption of calcium favoring the
      microenvironment necessary for bone mineralization. In addition, vitamin D
      prevents hypocalcemia via its osteoclastic action. Severe hypovitaminosis leads
      to rickets in children and its equivalent in adults, osteomalacia. Mild to
      moderate hypovitaminosis D causes secondary hyperparathyroidism increasing the
      risk of fracture, particularly femoral neck fracture. Vitamin D would also have
      an antiinflammatory and anticancer effect. WORLDWIDE: Hypovitaminosis D is
      frequently observed in Europe in the elderly, particularly in the
      institutionalized population, but is also seen in otherwise healthy younger
      adults. An estimated 40% of the young European population has some degree of
      hypovitaminosis D. Surprisingly, it is more frequent in sunny Mediterranean
      countries than in certain northern countries such as Norway. The lower incidence
      observed in the United States is probably related to the vitamin D
      supplementation of the American diet. Hypovitaminosis D in Africa and the Middle
      East is also an important problem, being considered to be one of the 5 most
      prevalent childhood diseases in developing countries. ENVIRONMENTAL FACTORS: The
      limited quantity of vitamin D in food and multiple environmental factors
      contribute to hypovitaminosis D. These factors include insufficient sun exposure
      and urban lifestyle with a high degree of pollution. In addition, cutaneous
      photosynthesis of vitamin D is limited by hyperpigmentation in black people,
      wearing traditional veils that limit sun exposure, and use of sun lotions,
      further contributing to vitamin D deficiency. CONCLUSIONS AND RECOMMENDATIONS:
      The very high prevalence of hypovitaminosis D in the world, and particularly in
      Europe, Africa and the Middle-East, points to the need for public health measures
      in these countries. While waiting for these measures to be implemented, vitamin D
      supplementation (for example in tablet form) should be encouraged in order to
      meet minimum requirements. Finally, the beneficial effect of moderate sun
      exposure on cutaneous vitamin D synthesis (and psychological well-being) must not
      be overlooked.

PMID- 11346910
TI  - [Topical corticosteroids, a timely class of drugs. A new class II topical
      corticosteroid: fluticasone propionate].

PMID- 11346911
TI  - [Disorders of lipid metabolism in 3 patients with diabetes mellitus type 2].
AB  - Three patients with diabetes mellitus (type 2) and cardiovascular disease had
      disturbed lipid concentrations: two women aged 60 and 73 years and one man aged
      47 years. The lipid levels were normalised during the 9-18 years of treatment
      with medication and in this period the patients experienced no cardiovascular
      events. Disturbances in plasma lipid levels play a major role in the increased
      risk of cardiovascular disease in patients with diabetes mellitus (type 2).
      Cholesterol-lowering treatment should be aggressive and based on the lipid
      profile. Statins reduce cardiovascular events by lowering the concentration of
      both the total cholesterol and low-density lipoprotein cholesterol whereas
      fibrates reduce cardiovascular events by increasing high-density lipoprotein
      cholesterol concentrations and lowering triglyceride concentrations.

PMID- 11346912
TI  - [Embolization of uterine artery: a new treatment for uterine myomas].
AB  - Uterine myomas are a common cause of menorrhagia and other complaints, and a
      common indication for hysterectomy. For several years now, bilateral uterine
      artery embolisation has been applied as an alternative to surgery. The
      effectiveness of this treatment modality in controlling abnormal bleeding
      patterns and in reducing uterine size, as described in early reports, seems to be
      confirmed in larger series of patients. However, the disadvantages have also
      become apparent, with subsequent ovarian failure and sepsis being the most
      worrisome complications. Data from randomised clinical trials comparing uterine
      embolisation versus hysterectomy in the treatment of uterine myomas are still
      lacking.

PMID- 11346913
TI  - [Dyslipidemia in diabetes mellitus].
AB  - Patients with diabetes mellitus are at high risk of cardiovascular diseases.
      Dyslipidemia is an important risk factor for cardiovascular complications in
      diabetes. Increased triglyceride and reduced HDL-cholesterol plasma
      concentrations are common features of dyslipidemia in type 2 diabetes. The LDL
      particles are small and dense and have an increased atherogenity. Abnormalities
      in lipoprotein composition are observed in diabetes mellitus, especially in type
      2. Post-hoc subgroup analyses of studies on the effect of lipid-lowering therapy
      on cardiovascular events suggest that treatment of dyslipidemia in diabetes may
      prevent cardiovascular complications. There are increasing indications that
      dyslipidemia in diabetes mellitus deserves aggressive treatment and that lipid
      target levels should be very low.

PMID- 11346914
TI  - [Physical diagnostics--duplex scanning is necessary only for selected patients
      with varicose veins].
AB  - With the advent of non-invasive duplex scanning, the imaging of the lower limb
      venous system has been greatly improved. Some authors routinely use duplex on
      their patients with varicose veins. However, this policy is associated with
      increased costs and demands a lot of logistics as well as the radiologists' time
      in clinics treating many of these patients. In view of the small difference in
      diagnostic accuracy compared to venography, duplex scanning is the gold standard
      for diagnosing patients with varicose veins in current practice. Recently the
      cheaper and simpler Doppler testing was compared with duplex scanning. In
      patients with primary varicose veins who have not previously been operated on,
      physical examination combined with Doppler can indicate more than 90% of V.
      saphena magna insufficiencies. However, Doppler misses approximately one-third of
      insufficient V. saphena parva (VSPs) and it is unable to localize the variable
      saphenopopliteal junction accurately. Since the incidence of VSP insufficiency in
      patients with primary varicose veins is only 15-33%, physical examination
      combined with Doppler investigation is sufficient to establish the correct
      diagnosis in the majority of patients. For recurrent varices, the sensitivity,
      specificity and negative predictive value of a Doppler investigation is marginal.
      In practice, duplex scanning is only indicated as follows; when VSP insufficiency
      is suspected, for recurrent varices, when signs of chronic venous insufficiency
      are present and when the findings from a physical examination combined with
      Doppler tests are inconclusive, e.g. in patients with adipose legs.

PMID- 11346915
TI  - [Diagnostic image (34). Echinococcal cysts in the liver].
AB  - A 56-year-old man, from Turkey, with upper abdominal pain and nausea had an
      echinococcal cyst in the liver.

PMID- 11346916
TI  - [From gene to disease; from DNA 'mismatch' repair genes to hereditary non
      polyposis colorectal carcinoma].
AB  - Hereditary non-polyposis colorectal cancer (HNPCC), also known as Lynch syndrome,
      is the most common autosomal dominant condition associated with early-onset
      colorectal cancer and the occurrence of cancer at other anatomical sites, i.e.
      endometrium, stomach, small intestine, urinary tract and ovaries, at an early
      age. Germline mutations in one of five DNA mismatch repair genes: MSH2, MLH1,
      PMS1, PMS2, and MSH6, predispose to HNPCC. Tumours of HNPCC patients display a
      high level of genomic instability, usually observed as changes in repeat numbers
      of simple repetitive sequences (microsatellite instability), which is a
      reflection of the malfunction of the DNA mismatch repair machinery.

PMID- 11346917
TI  - [Intracavernous auto-injection therapy with papaverine phentolamine via an auto
      injection pen for patients with an erectile dysfunction: similar results achieved
      in family practice and urology].
AB  - OBJECTIVE: To determine the results of an auto-injection therapy with papaverine
      phentolamine (using an auto-injection pen) prescribed by a GP or a urologist, in
      patients with erectile dysfunction. DESIGN: Prospective, comparative,
      descriptive. METHOD: A total of 603 men with erectile dysfunction who were
      prescribed papaverine-phentolamine auto-injection by 59 GPs and 76 urologists
      participated in the study. The physician completed a questionnaire at the first
      visit and during the three follow-up visits (the last at 6 months) and the
      patient kept a diary and gave a satisfaction score on a nine-point scale.
      RESULTS: The cause of the erectile dysfunction was most commonly
      psychogenic/mixed somatic-psychogenic in the GP group and most commonly vascular
      in the urologist group (p > 0.05). The somatic comorbidity was the same (70%),
      whereas the prevalence of psychological symptoms differed (GP group: 6%;
      urologist group: 7%; p < 0.001). Attendance at all of the follow-up examinations
      was 38% for the GP group and 17% for the urologist group. The mean starting dose
      in the GP group was 0.49 ml and in the urologist group 0.70 ml (p < 0.001). The
      mean end dose was the same (about 1 ml). The frequency of adverse reactions was
      9%: haematoma (5%), prolonged erection (1.8%). During the course of the
      investigation, 38% of the patients (31% in the GP group; 40% in the urologist
      group) discontinued the treatment owing to a limited effect, adverse reactions,
      difficult administration or problems related to the partner. In both the GP and
      the urologist group, 72% of the patients and 77% of the partners were satisfied
      or very satisfied with the auto-injection pen treatment. The patient's mean
      satisfaction score was 7.2. CONCLUSION: Whether the patient was treated by a GP
      or a urologist, the auto-injection therapy with papaverine-phentolamine for
      erectile dysfunction, using an auto-injection pen, was well tolerated and was
      highly appreciated by both the patients and their partners. Nevertheless one
      third of the patients discontinued the treatment prior to the end of the study.
      The mean end dose of the medication was the same in both groups.

PMID- 11346918
TI  - [Disappointing long-term experiences of patients with penile prosthesis].
AB  - OBJECTIVE: To describe the long-term experience with the implantation of a penile
      prosthesis as a last resort treatment for erectile dysfunction. DESIGN:
      Retrospective and descriptive. METHOD: During the period 1986-1996, 124 men
      received a penile prosthesis. Basic information was obtained from medical files.
      Seventy-six men could be traced and were sent a questionnaire. Sixty patients and
      44 partners participated in the study. RESULTS: The median time since the
      implantation was 81.3 months (range: 13-139). The chance of reoperation was 35%.
      Seventeen percent of the patients and 25% of the spouses regretted the decision
      to have the implantation. Thirty-one percent no longer used the prosthesis and
      15% had never used it. Twenty percent of the patients and 31% of the partners
      noticed an improvement in their sexual relationship whereas 26% and 23%
      respectively noticed a decline. Twenty percent of the patients sometimes failed
      to penetrate despite the prosthesis. Nevertheless, 66% would advise implantation
      to someone else. Almost 50% of the men reported spontaneous tumescence during
      sexual arousal. CONCLUSION: After the implantation of a penile prosthesis, the
      reoperation rate was high, and many patients and their partners were dissatisfied
      with their sexual relationship despite regaining a functional erection.
      Implantation requires thorough sexological counselling both before and after the
      operation.

PMID- 11346920
TI  - Internal carotid artery occlusion following sports diving.
AB  - A case of internal carotid artery occlusion following a sports dive is described.
      The investigation and management of this condition is discussed with particular
      reference to blunt trauma being a risk factor for carotid artery occlusion.

PMID- 11346919
TI  - [Embolization as treatment for symptomatic uterus myomata].
AB  - Selective percutaneous embolisation of the uterine arteries was carried out on
      three women with hypermenorrhea caused by uterine myomata. Two of the patients
      experienced resumption of the normal menstrual pattern. In the first case the
      myoma became 30% smaller and in the second case, the fibroid was expelled into
      the vagina six months later. The third patient suffered a fever one week after
      the treatment due to an infected necrotic myoma, after which a hysterectomy was
      carried out. The embolisation of myomata can offer an alternative to medicinal
      treatment, myomectomy or hysterectomy. The advantages of embolisation compared to
      a hysterectomy are a shorter hospital admission time, quick recovery after the
      procedure and retention of the uterus.

PMID- 11346921
TI  - The lethal ten per cent burn.

PMID- 11346922
TI  - Electrocardiographic changes following primary blast injury to the thorax.
AB  - Profound physiological changes occur following primary blast exposure but the
      contribution of cardiac arrhythmias is unknown. Thirteen rats, under intravenous
      anaesthesia, were exposed to a blast wave directed at the thorax (Group II); 10
      other animals underwent abdominal blast (Group III) and nine animals acted as
      controls (Group I). Animals were monitored before, during and after blast
      exposure. Group II animals demonstrated apnoea, bradycardia and hypotension. No
      significant physiological changes were seen in Groups I or III. Group II
      displayed a variety of ECG disturbances, from ventricular extrasystoles to
      ventricular fibrillation. All abnormalities reverted to sinus rhythm within
      minutes except in fatally injured animals. These ECG changes probably result from
      stress wave injury. Significant disturbances might account for some fatalities
      following primary blast exposure and may exacerbate the triad of apnoea,
      bradycardia and hypotension. Such observations may have important consequences
      for the management of blast casualties.

PMID- 11346923
TI  - Who is watching over me?--was the public's perception of the anaesthetist changed
      by National Anaesthesia Day?
AB  - The aim of National Anaesthesia Day on 25 May 2000 was to inform the public about
      the role and training of anaesthetists. We carried out two surveys of patients
      attending Derriford Hospital, Plymouth to assess the local impact of National
      Anaesthesia Day and to assess the public's expectation of the preoperative visit.
      The first survey was held one month prior to National Anaesthesia Day and was
      completed by 93 patients. The second survey was held immediately following
      National Anaesthesia Day and was completed by 70 patients. Thirty five percent of
      the patients surveyed were unaware that anaesthetists were medically qualified.
      This result was not altered by National Anaesthesia Day despite a local
      information campaign. Moreover, knowledge about our role and training was only
      marginally improved from 1978. The majority of patients expected to see their
      anaesthetist preoperatively for less than 10 minutes and would not be concerned
      if they had not been seen one hour before surgery. Style of clothing was
      unimportant; few preferred a white coat but name badges were desirable. We
      conclude that the level of ignorance about our profession has not changed since
      1978 and the impact of National Anaesthesia Day was not significant. This may be
      as a result of the anaesthetist's portrayal on television, which is known to be
      an important source of public information on other areas of medicine. If these
      statistics are to change in the next 22 years new methods of public education
      need to be found.

PMID- 11346924
TI  - A fish out of water--medical support for British Army exercises in northern
      Poland.

PMID- 11346925
TI  - The submarine service of the future?
AB  - Space missions, although now routine, are unique in terms of their environment
      and logistical requirements. The number of missions (man-hours) remains
      relatively small and planning still relies on comparisons with analogous
      missions, including submarine operations. Antarctic missions, which tend not to
      be classified, have provided more information about isolated communities because
      of the number of personnel per base. Space medicine has traditionally been an
      extension of aviation medicine with high g-forces involved in the transition from
      Earth to orbit and astronauts such as Neil Armstrong recruited from the test
      pilot fraternity. As the length of a mission increases and the space habitation
      relies more on regenerative systems, the environment becomes more analogous with
      today's nuclear submarines. As well as the air purification implications,
      radiation still is a significant hazard with even greater impact on future Mars
      missions requiring the provision of health physics monitoring, advice and
      countermeasures well established in the submarine flotilla. Nevertheless, the
      specialty space medicine will progress as a specialty in its own right, pooling
      expertise from other specialties such as aviation, radiation, emergency and
      occupational medicine taking human exploration beyond the confines of land and
      sea.

PMID- 11346926
TI  - Fleet first.

PMID- 11346927
TI  - Doctor's orders no. 9--or 10 green bottles skulking in the hulk?

PMID- 11346928
TI  - The British Services Kangchenjunga Expedition 2000.

PMID- 11346929
TI  - Helicopter medical retrieval in Sydney, New South Wales.
AB  - Undoubtedly the main attraction of this job is the interest of never knowing what
      will happen next! Primary response to an MVA allows one to experience the
      atmosphere and deal with clinical situations in an alien setting. This broadens
      ones perspective and has taught me never to be tempted to criticise a paramedic
      bringing a patient into a resus room. The same is true of interhospital transfers
      where tact and diplomacy can be tested as well as clinical skills. On the
      negative side the unpredictability can be difficult domestically (a primary at
      17555 means you will be at least two hours late home) and there can be long and
      dull days when nothing happens. A lot of time is spent transporting post arrest
      patients from one hospital to another to find an ICU bed. In military medicine it
      is difficult to envisage a future conflict when severely injured casualties would
      not require transport both locally and over long distances. This job provides an
      ideal opportunity to become confident with transporting critically ill patients.

PMID- 11346930
TI  - Are older lymphoma and breast cancer patients undertreated?

PMID- 11346931
TI  - The role of irinotecan and oxaliplatin in the treatment of advanced colorectal
      cancer.
AB  - Colorectal carcinoma is one of the most common malignancies in the western world,
      and although fluorouracil (5-FU) has been used in its treatment for almost 40
      years, new agents with significant activity have been introduced recently.
      Irinotecan (CPT-11, Camptosar), a topoisomerase I inhibitor, administered at 300
      to 350 mg/m2 every 3 weeks is significantly more active than continuous-infusion
      5-FU in patients who have experienced disease progression after conventional
      therapy with 5-FU. In comparison to best supportive care, irinotecan improves
      survival and preserves quality of life despite treatment-related toxicity.
      Moreover, the combination of irinotecan and 5-FU has been explored in a number of
      different schedules. In previously untreated patients, overall response rates are
      high. Irinotecan can also be combined with mitomycin (mitomycin-C [Mutamycin]),
      oxaliplatin, or raltitrexed (Tomudex). Oxaliplatin is a new-generation platinum
      compound that has demonstrated activity against colorectal carcinoma in
      preclinical trials. It has been evaluated as a single agent against advanced
      colorectal carcinoma in the salvage setting and also in combination with 5-FU as
      initial therapy for metastatic disease (where it shows significant activity). The
      toxicity profile of oxaliplatin (chiefly characterized by neurotoxicity) differs
      from that of irinotecan (primarily producing diarrhea) and the potential,
      therefore, exists for combining these agents or for exploiting their possible
      synergy with 5-FU. The introduction of these two new active agents of different
      pharmacologic classes promises to enable significant improvements in the
      treatment of patients with colorectal carcinoma.

PMID- 11346933
TI  - Clinical trials referral resource. Health related quality of life in cancer
      clinical trials.

PMID- 11346932
TI  - AIDS-related cancers in the era of highly active antiretroviral therapy.
AB  - Highly active antiretroviral therapy (HAART) has shown great efficacy in reducing
      human immunodeficiency virus levels, increasing immunity, and prolonging the
      survival of persons with acquired immunodeficiency syndrome (AIDS). The risk of
      life-threatening infections has been greatly reduced. However, the impact of
      HAART on the incidence of malignancy has been less clear. Published studies
      generally show that the risk of developing Kaposi's sarcoma declined by about two
      thirds between 1994 and 1995 and from 1996 onward (considered the HAART era).
      Even before 1994, the risk for Kaposi's sarcoma in persons with AIDS had declined
      considerably and this cancer has now become relatively uncommon. The mechanism by
      which this decline in incidence was achieved appears to involve improved
      immunity. Data on the reduction in the risk for non-Hodgkin's lymphoma are mixed.
      Several studies conducted between 1997 and 1999 found no reduction in the risk
      for non-Hodgkin's lymphoma, although the most recent data (from 1997 to 1999)
      show a 42% decrease in risk. Even with a one-third reduction, the risk for non
      Hodgkin's lymphoma remains considerably elevated. This high risk may be related
      to the fact that HAART therapy does not restore the immune system to normalcy.
      The increased lymphocyte turnover, with its accompanying risk of genetic errors,
      may increase the risk of developing non-Hodgkin's lymphoma. Most reports have
      insufficient data to analyze the impact of HAART therapy on incidence of central
      nervous system lymphomas, but recent data (from 1997 to 1999) showed a
      significant reduction in that risk. The mechanism by which this might occur is
      unclear because the central nervous system is an immunologic sanctuary. The
      relatively low incidence of other cancers in persons with AIDS makes it difficult
      to gauge the effect of HAART on their incidence, but to date, no significant
      trends have been reported for specific tumor types or for the overall risk of non
      AIDS-related cancers.

PMID- 11346934
TI  - Current status of radiation in the treatment of breast cancer.
AB  - Radiation therapy in combination with lumpectomy and axillary dissection has
      remained standard therapy for early-stage disease since the 1970s. Although there
      has been no definitive trial in patients with ductal carcinoma in situ, the data
      suggest that excision plus radiation therapy is a viable option. The local
      management of early-stage breast cancer includes modified radical mastectomy,
      with or without reconstruction, or breast-conserving therapy. Six prospective
      randomized trials compared mastectomy with breast-conserving therapy, and all
      have shown equivalent survival. Despite efforts to identify subgroups of patients
      with invasive disease who do not require breast irradiation, based on current
      data, this modality remains standard treatment after conservative surgery in all
      patients. Ongoing multicenter studies may clarify the role of brachytherapy,
      which may provide advantages in some patients after breast-conserving therapy.
      Axillary radiation is a viable option for patients who fail to undergo sampling
      of the axilla and may be a future option for patients who have a positive
      sentinel node but no further dissection. The ability of postmastectomy radiation
      to affect survival has long been controversial.

PMID- 11346935
TI  - Current management of cancer-associated anorexia and weight loss.
AB  - Loss of appetite and weight predict a poor prognosis for cancer patients.
      Although caloric supplementation might benefit subgroups of patients-
      specifically, perioperative, severely malnourished cancer patients, stem cell and
      bone marrow transplant patients and head and neck cancer patients--its use
      remains controversial and is not recommended for the majority of patients with
      cancer-associated weight loss.  Most patients with advanced cancer, anorexia,
      and/or weight loss do not appear to benefit from nutritional supplementation. 
      Instead, discussions with patients and families about realistic eating goals ans,
      at time armacologic interventions with progestational agents or corticosteroids-
      both of which are aimed at palliating anorexia--provide clinical benefit.  Other
      phamalogic interventions such as eicosapentaenoic acid, thalidomide (Thalomid),
      adenosine triphosphate and nonsteriodal anti-inflammatory agents focus on the
      fact that cancer-assciated weight loss is an enitty dintinct for simple
      starvation  These interventions promise to replenish lean tissue but require
      further investigation before they can be recommndedas standard clinical practice.

PMID- 11346936
TI  - Conservative management of rectal cancer with local excision and adjuvant
      therapy.
AB  - The standard surgical treatment of distal, resectable, invasive rectal cancers is
      an abdominoperineal resection or a low anterior resection. Given the morbidity
      associated with these standard treatments and the frequent need for postoperative
      adjuvant therapy, the use of a more conservative approach, such as local excision
      with adjuvant therapy as primary therapy for selected cases of rectal cancer is
      appealing. Data from single-institution series as well as recent data from
      prospective, multi-institutional studies, suggest that local excision with
      adjuvant therapy is a reasonable alternative to radical surgery in selected
      patients. Local excision alone is acceptable treatment only for T1 tumors without
      adverse pathologic features, while local excision with adjuvant therapy is an
      alternative treatment for T1 tumors with adverse pathologic features and T2
      tumors. Some series suggest that preoperative therapy with local excision may be
      a possible treatment for selected T3 tumors; however, the high local failure
      rates seen in T3 tumors treated with local excision and postoperative therapy
      cautions against this approach. Functional results with local excision are
      generally good, and postoperative morbidity and mortality is acceptable. In
      summary, the results of local excision and radiation therapy are encouraging.
      Randomized trials are needed to determine whether this approach has local control
      and survival rates comparable to those of radical surgery.

PMID- 11346937
TI  - Differential expression of triplicate phosphoribosylanthranilate isomerase
      isogenes in the tryptophan biosynthetic pathway of Arabidopsis thaliana (L.)
      Heynh.
AB  - Phosphoribosylanthranilate isomerases (PAI) in the tryptophan biosynthetic
      pathway of Arabidopsis thaliana are encoded by a gene family. Expression patterns
      of each individual PAI isogene were investigated by analyzing expression of
      translation-fusions of promoter-beta-glucuronidase (GUS) chimeras in transgenic
      plants. Quantification and histochemical staining of GUS activities expressed in
      PAI transgenic plants demonstrated that, first, expression of the three PAI
      isogenes was differentially regulated under normal growth conditions. Both PAI1
      and PAI3 showed approximately 10-fold stronger expression than PAI2. Second, PAI
      isogenes differentially responded to environmental stresses such as ultraviolet
      irradiation and the abiotic elicitor silver nitrate. PAI2 displayed a stronger
      response to stresses than the other two PAI isogenes. Third, each individual PAI
      isogene was differentially expressed in a tissue- and cell-type-specific manner.
      Fourth, expression of PAI isogenes was coordinated to meet the requirement for
      normal growth and development of A. thaliana. Deletion of PAI1 is partially
      responsible for abnormal growth and development in the PAI deletion mutant trp6
      as well as strong blue fluorescence in young leaves under ultraviolet
      irradiation.

PMID- 11346938
TI  - Cell wall deposition during morphogenesis in fucoid algae.
AB  - Cell was deposition was investigated during morphogenesis in zygotes of Pelvetia
      compressa (J. Agardh) De Toni. Young zygotes are spherical and wall is deposited
      uniformly, but at germination (about 10 h after fertilization) wall deposition
      becomes localized to the apex of the tip-growing rhizoid. Wall deposition was
      investigated before and after the initiation of tip growth by disrupting
      cytoskeleton, secretion or cellulose deposition; effects on wall strength and
      structure were examined. All three were involved in generating wall strength in
      both spherical and tip-growing zygotes, but their relative importance were
      different at the two developmental stages. Much of the wall strength in young
      zygotes was dependent on F-actin, whereas cellulose and a sulfated component,
      probably a fucan (F2), were most important in tip growing zygotes. Some
      treatments had contrasting effects at the two developmental stages; for example,
      disruption of F-actin or inhibition of secretion weakened walls in spherical
      zygotes but strengthened those in tip-growing zygotes. Transmission electron
      microscopic analysis showed that most treatments that altered wall strength
      induced modifications of internal wall structure.

PMID- 11346939
TI  - Brassinosteroids, microtubules and cell elongation in Arabidopsis thaliana. I.
      Molecular, cellular and physiological characterization of the Arabidopsis bull
      mutant, defective in the delta 7-sterol-C5-desaturation step leading to
      brassinosteroid biosynthesis.
AB  - Although cell elongation is a basic function of plant morphogenesis, many of the
      molecular events involved in this process are still unknown. In this work an
      extremely dwarf mutant, originally named bul, was used to study one of the main
      processes of plant development, cell elongation. Genetic analyses revealed that
      the BUL locus was linked to the nga172 marker on chromosome 3. Recently, after
      mapping the new dwf7 mutation of Arabidopsis, which is allelic to ste1, it was
      reported that dwf7 is also linked to the same marker. Sterol analyses of the bull
      1 mutant indicated that bul1-1 is defective in the delta 7-sterol-C5-desaturation
      step leading to brassinosteroid biosynthesis. Considering these findings, we
      designated our bul mutant as bul1-1/dwf7-3/ste1-4. The bul1-1 mutant was
      characterized by a very dwarf phenotype, with delayed development and reduced
      fertility. The mutant leaves had a dark-green colour, which was probably due to
      continuous stomatal closure. The bul1-1 mutant showed a partially de-etiolated
      phenotype in the dark. Cellular characterization and rescue experiments with
      brassinosteroids demonstrated the involvement of the BUL1-1 protein in
      brassinosteroid-dependent plant growth processes.

PMID- 11346940
TI  - Brassinosteroids, microtubules and cell elongation in Arabidopsis thaliana. II.
      Effects of brassinosteroids on microtubules and cell elongation in the bul1
      mutant.
AB  - In order to elucidate the involvement of brassinosteroids in the cell elongation
      process leading to normal plant morphology, indirect immunofluorescence and
      molecular techniques were use to study the expression of tubulin genes in the
      bul1-1 dwarf mutant of Arabidopsis thaliana (L.) Heynh., the characteristics of
      which are reported in this issue (M. Catterou et al., 2001). Microtubules were
      studied specifically in the regions of the mutant plant where the elongation zone
      is suppressed (hypocotyls and petioles), making the reduction in cell elongation
      evident. Indirect immunofluorescence of alpha-tubulin revealed that very few
      microtubules were present in mutant cells, resulting in the total lack of the
      parallel microtubule organization that is typical of elongating cells in the wild
      type. After brassinosteroid treatment, microtubules reorganized and became
      correctly oriented, suggesting the involvement of brassinosteroids in microtubule
      organization. Molecular analyses showed that the microtubule reorganization
      observed in brassinosteroid-treated bul1-1 plants did not result either from an
      activation of tubulin gene expression, or from an increase in tubulin content,
      suggesting that a brassinosteroid-responsive pathway exists which allows
      microtubule nucleation/organization and cell elongation without activation of
      tubulin gene expression.

PMID- 11346941
TI  - Cambial reactivation in locally heated stems of the evergreen conifer Abies
      sachalinensis (Schmidt) masters.
AB  - A study was made of cambial activity, the localization of storage starch around
      the cambium, and the localization and occurrence of microtubules in cambial cells
      from dormancy to reactivation in locally heated (22-26 degrees C) stems of the
      evergreen conifer Abies sachalinensis. Heating induced localized reactivation of
      the cambium in the heated portions of the stem. Erect ray cambial cells resumed
      cell division 1 d prior to the reactivation of fusiform cambial cells and
      procumbent ray cambial cells. The re-initiation of the division of fusiform
      cambial cells occurred first on the phloem side. During the heat treatment, the
      amount of storage starch decreased in procumbent ray cambial cells and in the
      phloem parenchyma adjacent to the cambium but increased in fusiform cambial
      cells. Preprophase bands of microtubules, spindle microtubules and phragmoplast
      microtubules were observed both in erect ray cambial cells and in procumbent ray
      cambial cells. By contrast, no evidence of the presence of such preprophase bands
      of microtubules was detected in fusiform cambial cells. The results suggest that
      the localized heating of stems of evergreen conifers might provide a useful
      experimental model system for studies of the dynamics of cambial reactivation in
      intact trees.

PMID- 11346942
TI  - Microinjection reveals cell-to-cell movement of green fluorescent protein in
      cells of maize coleoptiles.
AB  - During the evaluation of dual-purpose plant/fungal expression systems, we found
      that green fluorescent protein (GFP) has the ability to move from cell to cell in
      the epidermis of Zea mays L. cv. Mutator coleoptiles as well as into underlying
      cortical cells. Movement of GFP was observed both when DNA encoding GFP and
      bacterially expressed GFP were microinjected into epidermal cells. This suggests
      that GFP is capable of cell-to-cell movement. From experiments using dextrans of
      known molecular weight linked to fluorescein isothiocyanate and
      tetramethylrhodamine isothiocyanate, we estimate that the plasmodesmata of these
      cells have a size exclusion limit < 4.4 kDa. Cell-to-cell GFP movement did not
      occur when GFP was altered to include a nucleus- or endoplasmic reticulum
      retention sequence. The fact that these transcripts differ from that of
      cytoplasmic GFP by a small number of nucleotides suggests that the transcripts
      are not capable of movement, but movement of nucleic acid cannot be excluded.
      Since GFP is widely used to study cell-to-cell movement and to localize the
      expression of transgenes, caution should be exercised when interpreting results
      where GFP expression is used for localization.

PMID- 11346943
TI  - Leaf chlorosis in oilseed rape plants (Brassica napus) grown on cadmium-polluted
      soil: causes and consequences for photosynthesis and growth.
AB  - Brassica napus L. (oilseed rape) was grown from seeds on a reconstituted soil
      contaminated with cadmium (100 mg Cd kg-1 dry soil), resulting in a marked
      chlorosis of the leaves which was investigated using a combination of
      biochemical, biophysical and physiological methods. Spectroscopic and
      chromatographic analyses of the photosynthetic pigments indicated that chlorosis
      was not due to a direct interaction of Cd with the chlorophyll biosynthesis
      pathway. In addition, mineral deficiency and oxidative stress were apparently not
      involved in the pigment loss. Leaf chlorosis was attributable to a marked
      decrease in the chloroplast density caused by a reduction in the number of
      chloroplasts per cell and a change in cell size, suggesting that Cd interfered
      with chloroplast replication and cell division. Relatively little Cd was found in
      the chloroplasts and the properties of the photosynthetic apparatus (electron
      transport, protein composition, chlorophyll antenna size, chloroplast
      ultrastructure) were not affected appreciably in plants grown on Cd-polluted
      soil. Depth profiling of photosynthetic pigments by phase-resolved photoacoustic
      spectroscopy revealed that the Cd-induced decrease in pigment content was very
      pronounced at the leaf surface (stomatal guard cells) compared to the leaf
      interior (mesophyll). This observation was consistent with light transmission and
      fluorescence microscopy analyses, which revealed that stomata density in the
      epidermis was noticeably reduced in Cd-exposed leaves. Concomitantly, the
      stomatal conductance estimated from gas-exchange measurements was strongly
      reduced with Cd. When plants were grown in a high-CO2 atmosphere (4,000
      microliters CO2 l-1), the inhibitory effect of Cd on growth was not cancelled,
      suggesting that the reduced availability of CO2 at the chloroplast level
      associated with the low stomatal conductance was not the main component of Cd
      toxicity in oilseed rape.

PMID- 11346944
TI  - Analysis of mustard trypsin inhibitor-2 gene expression in response to
      developmental or environmental induction.
AB  - Transcription analysis of a mustard (Sinapis alba L.) serine proteinase inhibitor
      gene revealed identical 5' termini of mRNAs synthesized during seed maturation
      and chemical or wounding induction. Polyadenylation of mRNAs on multiple or
      single sites differentiated gene expression, increasing the availability of
      stable mRNAs during seed maturation compared with chemical and wounding
      induction. Expression of the beta-glucuronidase (GUS)-encoding region of the UidA
      reporter gene, detected under the control of deleted segments of the region
      flanking on the 5' side the mit-2 gene, identified a stretch of about 520 bp
      essential for gene expression. The presence in this region of two ABRE motifs is
      relevant for plant response to gene induction. Expression of GUS was detectable
      under different induction stimuli in several organs such as seedlings and leaves
      and was active to varying extents in the vascular tissues and meristem.

PMID- 11346945
TI  - Stored cysteine proteinases start globulin mobilization in protein bodies of
      embryonic axes and cotyledons during vetch (Vicia sativa L.) seed germination.
AB  - Inhibition of protein synthesis by cycloheximide during vetch seed germination,
      did not prevent globulin breakdown as indicated by a decrease in vicilin- and
      legumin-specific immunosignals on Western blots. Protein bodies isolated from
      embryo axes and cotyledons of dry vetch (Vicia sativa L.) seeds using a non
      aqueous method were found to be free of cytoplasmic and organellar
      contaminations. Lysates of these purified protein bodies were capable of
      degrading globulins; this process was blocked by the cysteine proteinase (CPR)
      inhibitor iodoacetic acid. Protein bodies contained the papain-like CPR2 and
      CPR4, and the legumain-like CPR VsPB2. In vitro assays showed that albumin
      extracts from protein bodies degraded oligopeptide substrates in the PepTag-Assay
      and degraded the legumain substrate N-benzoyl-asparaginyl-p-nitroanilide. We
      conclude that, during germination, globulin mobilization is initiated by stored
      CPRs in protein bodies of embryonic axes as well as cotyledons, and that de-novo
      formed proteolytic enzymes mainly mediate bulk degradation of stored globulin in
      cotyledons after germination.

PMID- 11346946
TI  - Differential tissue-specific expression of cysteine proteinases forms the basis
      for the fine-tuned mobilization of storage globulin during and after germination
      in legume seeds.
AB  - The temporal and spatial distribution of cysteine proteinases (CPRs) was analyzed
      immunologically and by in situ hybridization to identify the CPRs involved in the
      initiation of storage-globulin degradation in embryonic axes and cotyledons of
      germinating vetch (Vicia sativa L.). At the start of germination several CPRs
      were found in protein bodies in which they might have been stored in the mature
      seeds. Cysteine proteinase 1 was predominantly found in organs like the radicle,
      which first start to grow during germination. Cysteine proteinase 2 was also
      present at the start of germination but displayed a less-specific histological
      pattern. Proteinase B was involved in the globulin degradation of vetch
      cotyledons as well. The histological pattern of CPRs followed the distribution of
      their corresponding mRNAs. The latter were usually detected earlier than the CPRs
      but the in situ hybridization signals were histologically not as restricted as
      the immunosignals. Proteolytic activity started in the radicle of the embryonic
      axis early during germination. Within 24 h after imbibition it had also spread
      throughout the whole shoot. At the end of germination, newly synthesized CPRs
      might have supplemented the early detectable CPRs in the axis. In the cotyledons,
      only the abaxial epidermis and the procambial strands showed proteinase
      localization during germination. Both CPR1 and CPR2, as well as the less common
      proteinase B, might have been present as stored proteinases. Three days after
      imbibition, proteolytic activity had proceeded from the cotyledonary epidermis
      towards the vascular strands deeper inside the cotyledons. The histochemical
      detection of the CPRs was in accordance with the previously described
      histological pattern of globulin mobilization in germinating vetch [Tiedemann J,
      et al. (2000)]. A similar link between the distribution of CPRs and globulin
      degradation was found in germinating seeds of Phaseolus vulgaris L. The
      coincidence of the histological patterns of globulin breakdown with that of the
      CPRs indicates that at least CPR1, CPR2 and proteinase B are responsible for bulk
      globulin mobilization in the seeds of the two legumes.

PMID- 11346947
TI  - A few molecules of zeaxanthin per reaction centre of photosystem II permit
      effective thermal dissipation of light energy in photosystem II of a
      poikilohydric moss.
AB  - The relationship between thermal dissipation of light energy (as indicated by the
      quenching of chlorophyll fluorescence), zeaxanthin availability and protonation
      reactions was investigated in the moss Rhytidiadelphus squarrosus (Hedw.) Warnst.
      In the absence of zeaxanthin and actinic illumination, acidification by 20% CO2
      in air was incapable of quenching basal, so-called F0 fluorescence either in the
      moss or in spinach (Spinacia oleracea L.) leaves. However, 1-s light pulses given
      either every 40, 60 or 200 s increased thermal dissipation as indicated by F0 and
      Fm quenching in the presence of 20% CO2 in air in the moss, but not in spinach
      while reaction centres of photosystem II (PSII) were photochemically open. In the
      moss, a few short light pulses, which were separated by prolonged dark times,
      were sufficient to raise zeaxanthin levels in the presence of 20% CO2 in air.
      Simultaneously, quantum efficiency of charge separation in PSII was decreased.
      Increasing the CO2 concentration beyond 20% further decreased quantum efficiency
      even in the absence of short light pulses. Under conditions optimal for
      fluorescence quenching, one molecule of zeaxanthin per reaction centre of PSII
      was sufficient to decrease quantum efficiency of charge separation in PSII by
      50%. Thus, in combination with a protonation reaction, one molecule of zeaxanthin
      was as efficient at capturing excitation energy as a photochemically open
      reaction centre. The data are discussed in relation to the interaction between
      zeaxanthin and thylakoid protonation, which enables effective thermal dissipation
      of light energy in the antennae of PSII in the moss but not in higher plants when
      actinic illumination is absent.

PMID- 11346949
TI  - Evidence for type II phytochrome-induced rapid signalling leading to
      cab::luciferase gene expression in tobacco cotyledons.
AB  - We studied the activation of cab gene expression by phytochrome-induced
      intercellular signalling and report insights into the mechanism of induction and
      outspread of a plant internal signal. By micro-beam irradiation techniques and
      use of a photon-imaging charge-coupled device (CCD) camera system we monitored
      cab::luciferase reporter gene expression in cotyledons of transgenic tobacco
      (Nicotiana tabacum L. cv. Xanthi) plants. We found that (i) the photoreceptor
      triggering intercellular signalling and reporter-gene expression is type II but
      not type I phytochrome, (ii) phytochrome in its far-red-absorbing (Pfr) form is
      necessary for the induction but not for the outspread of the signalling, (iii)
      red/far-red reversibility is restricted to the red-irradiated cells, and (iv) the
      phytochrome-induced signal spreads rapidly throughout the cotyledon and reaches
      its target cells within minutes.

PMID- 11346948
TI  - Energy dissipation in photosynthesis: does the quenching of chlorophyll
      fluorescence originate from antenna complexes of photosystem II or from the
      reaction center?
AB  - Dissipation of light energy was studied in the moss Rhytidiadelphus squarrosus
      (Hedw.) Warnst., and in leaves of Spinacia oleracea L. and Arabidopsis thaliana
      (L.) Heynh., using chlorophyll fluorescence as an indicator reaction. Maximum
      chlorophyll fluorescence of 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU)
      treated spinach leaves, as produced by saturating light and studied between and 
      20 degrees C, revealed an activation energy delta E of 0.11 eV. As this suggested
      recombination fluorescence produced by charge recombination between the oxidized
      primary donor of photosystem II and reduced pheophytin, a mathematical model
      explaining fluorescence, and based in part on known characteristics of primary
      electron-transport reactions, was developed. The model permitted analysis of
      different modes of fluorescence quenching, two localized in the reaction center
      of photosystem II and one in the light-harvesting system of the antenna
      complexes. It predicted differences in the relationship between quenching of
      variable fluorescence Fv and quenching of basal, so-called F0 fluorescence
      depending on whether quenching originated from antenna complexes or from reaction
      centers. Such differences were found experimentally, suggesting antenna quenching
      as the predominant mechanism of dissipation of light energy in the moss
      Rhytidiadelphus, whereas reaction-center quenching appeared to be important in
      spinach and Arabidopsis. Both reaction-center and antenna quenching required
      activation by thylakoid protonation but only antenna quenching depended on or was
      strongly enhanced by zeaxanthin. De-protonation permitted relaxation of this
      quenching with half-times below 1 min. More slowly reversible quenching,
      tentatively identified as so-called qI or photoinhibitory quenching, required
      protonation but persisted for prolonged times after de-protonation. It appeared
      to originate in reaction centers.

PMID- 11346950
TI  - Regulation of respiration in rotenone-treated tobacco cell suspension cultures.
AB  - Cells of Nicotiana tabacum L. suspension cultures were treated with the
      respiratory inhibitor rotenone, which specifically inhibits complex I activity of
      mitochondria. Rotenone retarded cell growth, as shown by decreases in fresh
      weight, dry weight and cell numbers on a suspension-volume basis. However, rates
      of the coupled respiration were higher in rotenone-treated compared to control
      cells when expressed on a fresh-weight basis. Rates of the rotenone-insensitive
      respiration increased substantially on both a fresh-weight and extractable
      cellular-protein basis 24 h after rotenone treatment. ATP/ADP ratios were not
      significantly different between control and rotenone-treated cells. Our results
      indicated that cells of tobacco suspension cultures were able to maintain a slow
      rate of growth and adequate ATP/ADP ratios without the operation of complex I.

PMID- 11346951
TI  - Isolation of cDNA and genomic DNA clones encoding a calmodulin-binding protein
      related to a family of ATPases involved in cell division and vesicle fusion.
AB  - Calmodulin (CaM), a primary Ca2+ receptor in all eukaryotic cells, is a
      multifunctional protein that functions by interacting with and modulating the
      activities of a wide variety of target proteins. Identifying and characterizing
      these CaM-binding target proteins is essential to define the pathways by which
      Ca(2+)-regulated signals are transduced. An Arabidopsis thaliana L. flower cDNA
      expression library constructed in lambda ZAPII was screened for CaM-binding
      proteins with 35S-labeled CaM. A partial cDNA whose encoded protein shares a high
      level of similarity with yeast CDC48p was isolated. A genomic clone was isolated
      using the partial length cDNA clone as a probe, and its nucleotide sequence was
      determined. The genomic DNA sequence was used to design oligonucleotide primers
      for polymerase-chain-reaction (PCR) experiments that facilitated cloning and
      reconstructing a full-length, 3.4-kb cDNA clone. The cDNA encodes a 111-kDa CaM
      interacting protein (CIP111) containing motifs characteristic of a diverse family
      of ATPases, including proteins involved in cell cycle regulation, protein
      degradation, and vesicle-mediated protein transport. A truncated fusion protein
      encoded by the carboxy-terminal region of CIP111 was produced in Escherichia coli
      and shown to bind CaM in a Ca(2+)-dependent manner by protein gel blot and
      affinity chromatography binding assays. Reverse-transcription PCR analyses
      demonstrated that CIP111 mRNA is expressed in all organs examined including
      flowers, siliques, floral stalks, leaves, and roots. DNA blot hybridization
      analyses indicate that a single-copy gene in Arabidopsis is likely to encode
      CIP111.

PMID- 11346952
TI  - Increased levels of adenine nucleotides modify the interaction between starch
      synthesis and respiration when adenine is supplied to discs from growing potato
      tubers.
AB  - To investigate the importance of the overall size of the total adenine nucleotide
      pool for the regulation of primary metabolism in growing potato tubers, freshly
      cut discs were provided with zero or 2 mM adenine in the presence of 1 or 100 mM
      [U-14C]glucose or 100 mM [U-14C]sucrose in the presence and absence of 20 mM
      orthophosphate (Pi). Adenine led to a 150-250% increase of the total adenine
      nucleotide pool, which included an increase of ADP, a larger increase of ATP and
      an increase of the ATP:ADP ratio. There was a 50-100% increase of ADP-glucose
      (ADPGlc), and starch synthesis was stimulated. Respiratory oxygen uptake was
      stimulated, and the levels of glycerate-3-phosphate, phosphoenolpyruvate and
      alpha-ketoglutarate decreased. The response to adenine was not modified by Pi. It
      is proposed that increased ATP stimulates ADPGlc pyrophosphorylase, leading to a
      higher rate of starch synthesis. The impact on starch synthesis is constrained,
      however, because increased ADP can lead to a stimulation of respiration and
      decline of glycerate-3-phosphate, which will inhibit ADPGlc pyrophosphorylase.
      The quantitative impact depends on the conditions. In the presence of 1 mM
      glucose, the levels of phosphorylated intermediates and the rate of starch
      synthesis were low. Adenine led to a relatively large stimulation of respiration,
      but only a small stimulation of starch synthesis. In the presence of 100 mM
      glucose, discs contained high levels of phosphorylated intermediates, low ATP:ADP
      ratios (< 3) and low rates of starch synthesis (< 20% of the metabolised
      glucose). Adenine led to marked increase of ATP and 2- to 4-fold stimulation of
      starch synthesis. Discs incubated with 100 mM sucrose already had high ATP:ADP
      ratios (> 8) and high rates of starch synthesis (> 50% of the metabolised
      sucrose). Adenine led to a further increase, but the stimulation was less marked
      than in high glucose. These results have implications for the function of
      nucleotide cofactors in segregating sucrose mobilisation and respiration, and the
      need for energy conservation during sugar-starch conversions.

PMID- 11346953
TI  - Suppression of the ribosomal L2 gene reveals a novel mechanism for stress
      adaptation in soybean.
AB  - Pseudomonas syringae pv. glycinea bacteria or zoospores of the fungus
      Phytophthora sojae were used to trigger a hypersensitive reaction (HR) in cell
      cultures of soybean (Glycine max [L.] Merr. cv. Williams 82). During a screen for
      genes that show an altered expression as a response to dying neighbour cells we
      have identified a gene fragment that is specifically but transiently down
      regulated in an HR. The corresponding cDNA codes for the ribosomal protein L2
      (rpL2) of 80S ribosomes, which is essential for the peptidyl-transferase
      activity. Two gene copies of rpL2 exist in soybean and both genes are
      transcribed. The temporary down-regulation of the rpL2 genes is followed by a
      transient block in the synthesis of new proteins as visualised by pulse-labelling
      experiments using 35S-amino acids. The same basic phenomenon was also found after
      treatment of soybean cells with other stress-causing compounds such as elicitors
      or heavy metals. It is suggested that the transient block in protein synthesis
      allows a more rapid depletion of, for example, signal molecules with a short half
      life time and thus leads to a faster adaptation of the cellular protein inventory
      to the new environmental conditions.

PMID- 11346954
TI  - Inhibiting expression of a tomato ripening-associated membrane protein increases
      organic acids and reduces sugar levels of fruit.
AB  - Tomato (Lycopersicon esculentum Mill.) ripening-associated membrane protein
      (TRAMP) is a channel protein of the membrane intrinsic protein (MIP) class
      encoded by the cDNA clone pNY507 [R.G. Fray et al. (1994) Plant Mol Biol 24: 539
      543]. It has been suggested that these proteins encode water channels or
      aquaporins. TRAMP mRNA accumulated in all tomato tissues tested and was elevated
      in fruit during post-anthesis development and again during ripening. Transgenic
      plants that constitutively expressed a TRAMP antisense RNA sequence were
      generated with a 94% reduction of endogenous TRAMP mRNA in fruit. They showed no
      obvious phenotype that could be associated with gross perturbation of water
      relations, but ripening fruit of these plants showed marked alterations in the
      normal pattern of accumulation of both organic acids and sugars. At the onset and
      during ripening, levels of the organic acids L-malate and citrate were
      significantly elevated while levels of D[+]-glucose and D[+]-fructose were
      reduced. Additional transgenic lines were generated with reduced TRAMP mRNA, and
      the phenotype of increased acids and reduced sugars during fruit maturation and
      ripening was shown to be reproducible and stably inherited. Fruit of plants that
      over-expressed TRAMP mRNA showed no significant alteration in the sugars or acids
      investigated. These results suggest a role for TRAMP in the movement of solutes
      between cell compartments.

PMID- 11346955
TI  - In vivo temperature dependence of cyclic and pseudocyclic electron transport in
      barley.
AB  - The effect of temperature on the rate of electron transfer through photosystems I
      and II (PSI and PSII) was investigated in leaves of barley (Hordeum vulgare L.).
      Measurements of PSI and PSII photochemistry were made in 21% O2 and in 2% O2, to
      limit electron transport to O2 in the Mehler reaction. Measurements were made in
      the presence of saturating CO2 concentrations to suppress photorespiration. It
      was observed that the O2 dependency of PSII electron transport is highly
      temperature dependent. At 10 degrees C, the quantum yield of PSII (phi PSII) was
      insensitive to O2 concentration, indicating that there was no Mehler reaction
      operating. At high temperatures (> 25 degrees C) a substantial reduction in phi
      PSII was observed when the O2 concentration was reduced. However, under the same
      conditions, there was no effect of O2 concentration on the delta pH-dependent
      process of non-photochemical quenching. The rate of electron transport through
      PSI was also found to be independent of O2 concentration across the temperature
      range. We conclude that the Mehler reaction is not important in maintaining a
      thylakoid proton gradient that is capable of controlling PSII activity, and
      present evidence that cyclic electron transport around PSI acts to maintain
      membrane energisation at low temperature.

PMID- 11346956
TI  - Promoter strength and tissue specificity effects on growth of tomato plants
      transformed with maize sucrose-phosphate synthase.
AB  - When sucrose-phosphate synthase (SPS; EC 2.4.1.14) is expressed in tomato
      (Lycopersicon esculentum Mill.) from a ribulose-1,5-bisphosphate carboxylase
      oxygenase (Rubisco) small subunit (rbcS) promoter, yields are often unchanged but
      when SPS is expressed from a Cauliflower Mosaic Virus 35S promoter, yield is
      enhanced up to 80%. Two explanations for this phenomenon are (i) that expression
      of SPS in tissues other than leaves accounts for the increased yield or (ii) that
      the lower level of expression directed by the 35S promoter is more beneficial
      than the high level of expression directed by the rbcS promoter. To test the
      first hypothesis, we conducted a reciprocal graft experiment, which showed that
      root SPS activity did not substantially affect growth. To test the second
      hypothesis, we conducted a field trial using a backcrossed, segregating,
      population of SPS-transformed plants derived from 35S and rbcS lines. The optimal
      dose of SPS activity for growth was approximately twice that of the wild type
      regardless of which promoter was used. The effect of SPS on growth was the result
      of a shift in partitioning of carbon among starch, sucrose, and ionic compounds
      (primarily amino acids), rather than of an increase in net photosynthesis.
      Excessive SPS activity resulted in a decreased rate of amino acid synthesis,
      which could explain the non-linear response of plant growth to the level of SPS
      expression.

PMID- 11346957
TI  - Inhibition of beta-amylase activity, starch degradation and sucrose formation by
      indole-3-acetic acid during banana ripening.
AB  - In order to observe the effect of indole-3-acetic acid (IAA) on carbohydrate
      metabolism, unripe banana (Musa acuminata AAA, cv. Nanicao) slices were
      infiltrated with the hormone and left to ripen under controlled conditions. The
      climacteric respiration burst was reduced by the action of IAA, and starch
      degradation and sucrose formation were delayed. Sucrose synthase (SuSy; EC
      2.4.1.13) and sucrose-phosphate synthase (SPS; EC 2.4.1.14) activities and
      transcript levels were not affected, indicating that prevention of sucrose
      accumulation was not related to sucrose-metabolizing enzymes. Impairment of
      sucrose synthesis could be a consequence of lack of substrate, since starch
      degradation was inhibited. The increase in activity and transcript level of beta
      amylase was delayed, indicating that this enzyme could be important in starch-to
      sucrose metabolism in bananas and that it might be, at least partially,
      controlled at the transcriptional level. This is the first report showing that
      IAA can delay starch degradation, possibly affecting the activity of hydrolytic
      enzymes such as beta-amylase (EC 3.2.1.2).

PMID- 11346958
TI  - Physiological basis of reduced AL tolerance in ditelosomic lines of Chinese
      Spring wheat.
AB  - Aluminum tolerance was assessed in the moderately Al-tolerant wheat (Triticum
      aestivum L.) cultivar Chinese Spring and a set of ditelosomic lines derived from
      Chinese Spring. Three ditelosomic lines lacking chromosome arms 4DL, 5AS and 7AS,
      respectively, exhibited decreased Al tolerance relative to the euploid parent
      Chinese Spring based on reduced root growth in Al-containing solutions. The
      physiological basis of the reduced Al tolerance was investigated. Measurements by
      inductively coupled argon plasma mass spectroscopy of root apical Al accumulation
      demonstrated that two of these three lines had a decreased ability to exclude Al
      from the root apex, the site of Al phytotoxicity. As Al-induced malate exudation
      has been suggested to be an important physiological mechanism of Al tolerance in
      wheat, this parameter was quantified and malate exudation was shown to be smaller
      in all three deletion lines compared with Chinese Spring. These results suggest
      that the decreased Al tolerance in at least two of the three ditelosomic lines is
      due to the loss of different genes independently influencing a single Al
      tolerance mechanism, rather than to the loss of genes encoding alternative Al
      tolerance mechanisms.

PMID- 11346959
TI  - A plasma membrane-bound enzyme of tobacco roots catalyses the formation of nitric
      oxide from nitrite.
AB  - Purified plasma membranes (PMs) of tobacco (Nicotiana tabacum L. cv. Samsun)
      roots exhibited a nitrite-reducing enzyme activity that resulted in nitric oxide
      (NO) formation. This enzyme activity was not detected in soluble protein
      fractions or in PM vesicles of leaves. At the pH optimum of pH 6.0, nitrite was
      reduced to NO with reduced cytochrome c as electron donor at a rate comparable to
      the nitrate-reducing activity of root-specific succinate-dependent PM-bound
      nitrate reductase (PM-NR). The hitherto unknown PM-bound nitrite: NO-reductase
      (NI-NOR) was insensitive to cyanide and anti-NR IgG and thereby proven to be
      different from PM-NR. Furthermore, PM-NR and NI-NOR were separated by gel
      filtration chromatography and apparent molecular masses of 310 kDa for NI-NOR and
      200 kDa for PM-NR were estimated. The PM-associated NI-NOR may reduce the
      apoplastic nitrite produced by PM-NR in vivo and may play a role in nitrate
      signalling via NO formation.

PMID- 11346960
TI  - Changes in the structure of xyloglucan during cell elongation.
AB  - Xyloglucans were isolated by sequential extraction of the cell walls of pea
      (Pisum sativum L. cv. Alaska) with a xyloglucan-specific endoglucanase and KOH.
      The xyloglucan content and xyloglucan-oligosaccharide composition were determined
      for fractions obtained from the elongating and non-elongating segments of pea
      stems grown in the light and in darkness. The results were consistent with the
      hypothesis that regulated growth of the cell wall depends on xyloglucan
      metabolism. Furthermore, the characterization of xyloglucan extracted from leaves
      of light-grown pea plants indicates that xyloglucan metabolism is tissue
      specific. Changes in xyloglucan subunit structure observed in elongating stems
      are consistent with the in muro realization of a metabolic pathway that was
      previously proposed solely on the basis of the in vitro activities of plant
      glycosyl hydrolases.

PMID- 11346961
TI  - Insertion of polydeoxyadenosine-rich sequences into an intergenic region
      increases transcription in Chlamydomonas reinhardtii chloroplasts.
AB  - In this study, chloroplast transformation in Chlamydomonas reinhardtii was used
      to insert a tract of polydeoxyadenosine, which is known to influence DNA
      structure and transcription in other systems, between the 3' end of the atpB
      gene, encoding the beta-subunit of the chloroplast ATP synthase, and a downstream
      chimeric gene, aadA, encoding antibiotic resistance. Run-on transcription and RNA
      analyses revealed that in cells containing (dA)40 and (dAAAGGG)8, aadA was
      transcribed at a higher rate, and its RNA accumulated to a relatively high level.
      It is concluded that poly(dA/dT) can function in the chloroplast as a
      transcription enhancer element. Therefore, the insertion of poly(dA/dT) sequence
      into the intergenic region of a multicistronic transcription unit may modulate
      gene expression at the transcriptional level.

PMID- 11346962
TI  - Heterotrimeric G-protein and signal transduction in the nematode-trapping fungus
      Arthrobotrys dactyloides.
AB  - The fungus Arthrobotrys dactyloides produces specialized constricting rings to
      trap and then consume nematodes. The signal transduction pathway involved in the
      nematode-trapping process was examined. Mastoparan, an activator of G-protein,
      had a stimulatory effect on the inflation of ring cells, whereas a G-protein
      inhibitor, pertussis toxin, prevented ring-cell expansion. The 40-kDa G alpha of
      heterotrimeric G-proteins was specifically ADP-ribosylated by pertussis toxin.
      Using an antibody specific to the 35-kDa subunit G beta, we showed that
      immunogold-labeled G beta was more concentrated in ring cells than in the hyphae.
      In the absence of nematodes, the rings could be inflated by either pressurizing
      the culture in a syringe, raising intracellular Ca2+ concentrations, or adding
      warm water. We used these methods to reveal differences in responses to
      antagonists. The results support a model in which the pressure exerted by a
      nematode on the ring activates G-proteins in the ring cells. The activation leads
      to an increase in cytoplasmic Ca2+, activation of calmodulin, and finally the
      opening of water channels. The ring cells expand to constrict the ring and thus
      immobilize the nematode.

PMID- 11346963
TI  - In vivo evidence that Ids3 from Hordeum vulgare encodes a dioxygenase that
      converts 2'-deoxymugineic acid to mugineic acid in transgenic rice.
AB  - We proposed that an Fe-deficiency-induced gene, Ids3 (Iron deficiency specific
      clone no. 3), from barley (Hordeum vulgare L.) roots encodes a dioxygenase that
      catalyzes the hydroxylation step from 2'-deoxymugineic acid (DMA) to mugineic
      acid (MA). To prove this hypothesis, we introduced the Ids3 gene into rice (Oryza
      sativa L.), which lacks Ids3 homologues and secretes DMA, but not MA. Transgenic
      rice plants, carrying either Ids3 cDNA or a barley genomic DNA fragment (20 kb)
      containing Ids3, were obtained using Agrobacterium-mediated transformation. Ids3
      cDNA under the control of the cauliflower mosaic virus 35S promoter was
      constitutively expressed in both the roots and the leaves of the transgenic rice,
      regardless of Fe nutrition status. In contrast, in the roots of transformants
      carrying a barley genomic fragment, transcripts of Ids3 were markedly increased
      in response to Fe deficiency. Slight expression of Ids3 was also observed in the
      leaves of the Fe-deficient plants. Western blot analysis confirmed the induction
      of Ids3 in response to Fe deficiency in the roots of the transformants carrying a
      genomic fragment. These expression patterns indicate that the 5'-flanking region
      of Ids3 works as a strong Fe-deficiency-inducible promoter in rice, as well as in
      barley. Both kinds of transgenic rice secreted MA in addition to DMA under Fe
      deficient conditions, but wild-type rice secreted only DMA. This is in vivo
      evidence that IDS3 is the "MA synthase" that converts DMA to MA.

PMID- 11346964
TI  - Transgenic expression of a delta 12-epoxygenase gene in Arabidopsis seeds
      inhibits accumulation of linoleic acid.
AB  - The Crepis palaestina cDNA Cpal2 encodes a delta 12-epoxygenase that can catalyse
      the synthesis of 12,13-epoxy-cis-9-octadecenoic acid (18:1E) from linoleic acid
      (18:2). When the Cpal2 gene was expressed under the control of the napin seed
      specific promoter in Arabidopsis thaliana (L.) Heynh., the seed lipids
      accumulated only low levels of 18:1E and also 12,13-epoxy-cis-9,15-octadec-2
      enoic acid (18:2E). Despite the fact that the levels of these epoxy fatty acids
      comprised only up to 6.2% of the total fatty acids, there was a very marked
      increase in oleic acid (18:1) and decrease in linoleic (18:2) and alpha-linolenic
      (18:3) acids in these plants, indicating that endogenous delta 12-desaturation
      was greatly reduced in these plants. Significant between-line differences in the
      levels of Cpal2 mRNA were observed during seed development, but were not
      associated with any major variation in mRNA levels for the endogenous Arabidopsis
      delta 12-desaturase (Fad2). This suggests that if an unfavourable interaction
      occurs between the transgenic delta 12-epoxygenase and the endogenous delta 12
      desaturase, which decreases the level of desaturation, it occurs at either the
      translational or post-translational level. We further show that the co-expression
      of a delta 12-desaturase gene from C. palaestina in Cpal2 transgenic Arabidopsis
      returns the relative proportions of the C18 seed fatty acids to normal levels and
      results in an almost twofold increase in total epoxy fatty acids.

PMID- 11346965
TI  - Metabolic response of potato plants to an antisense reduction of the P-protein of
      glycine decarboxylase.
AB  - Potato (Solanum tuberosum L. cv. Desire) plants with reduced amounts of P
      protein, one of the subunits of glycine decarboxylase (GDC), have been generated
      by introduction of an antisense transgene. Two transgenic lines, containing about
      60-70% less P-protein in the leaves compared to wild-type potato, were analysed
      in more detail. The reduction in P-protein amount led to a decrease in the
      ability of leaf mitochondria to decarboxylate glycine. Photosynthetic and growth
      rates were reduced but the plants were viable under ambient air and produced
      tubers. Glycine concentrations within the leaves were elevated up to about 100
      fold during illumination. Effects on other amino acids and on sucrose and hexoses
      were minor. Nearly all of the glycine accumulated during the day was metabolised
      during the following night. The data suggest that the GDC operates far below
      substrate saturation under normal conditions thus allowing a flexible and fast
      response to changes in the environment.

PMID- 11346967
TI  - 'No secrets, no excuses' policy leads hospital to performance excellence.
AB  - In 1995, Baptist Hospital in Pensacola, FL, found itself sandwiched between two
      larger health systems and facing a stagnant market. Like other hospitals, it also
      was confronting diminishing reimbursement, increasing regulatory requirements,
      and staffing shortages. Since then, the hospital has made dramatic gains in all
      its performance criteria and has become recognized as a national leader in
      quality innovation.

PMID- 11346966
TI  - WY-14,643 and other agonists of the peroxisome proliferator-activated receptor
      reveal a new mode of action for salicylic acid in soybean disease resistance.
AB  - Inoculation of soybean (Glycine max [L.] Merr.) cell-suspension cultures with
      avirulent bacteria results in a salicylic acid (SA)-controlled programmed cell
      death (pcd). To unravel the nature of the SA-dependent step in pcd, a screening
      procedure for complementing compounds was performed. Diverse chemicals that are
      well known as activating ligands for orphan receptors in animals, particularly
      receptors of the PPAR (peroxisome proliferator-activated receptor) subfamily,
      were found to be active. These include the compounds WY-14643, flufenamic acid,
      LY-171883, tolbutamide, indomethacin and clofibrate. A new marker gene (DD-CA9)
      from soybean that is induced in the hypersensitive reaction by SA and by PPAR
      ligands was isolated by differential display, and showed homology to antifungal
      lectins. In plants, SA is also involved in a signal transduction pathway leading
      to systemic acquired resistance (SAR). The PPAR ligands which act on the pcd
      pathway for plant resistance induce a beta-1,3-glucanase gene in soybean at high
      concentrations but do not induce marker genes of the SAR pathway such as the PR-1
      gene in tobacco or Arabidopsis. Thus SA seems to act on two independent plant
      defence pathways that can now be separately activated by synthetic compounds. We
      propose a model for the control of pcd by SA in soybean, in which SA induces the
      transcription of (novel) genes required for the final completion of the cell
      death program.

PMID- 11346968
TI  - Baldrige Award program gains favor with hospitals.
AB  - Hospitals seeking to improve their performance increasingly are turning to the
      ambitious criteria established by the Malcolm Baldrige National Quality Award.
      The Baldrige program was established by Congress in 1987 to raise awareness about
      the importance of quality and performance excellence. Many say the Baldrige
      criteria represent the most far-reaching quality improvement program now
      available.

PMID- 11346969
TI  - JCAHO proposes staffing effectiveness standards.
AB  - The Joint Commission on Accreditation of Healthcare Organizations has proposed a
      set of new standards aimed at assessing staffing effectiveness, which the Joint
      Commission defines as 'the number, competency, and skill mix of staff respecting
      the provision of needed services.' In a letter dated March 14, JCAHO president
      Dennis O'Leary, MD, solicited feedback from providers on the proposed standards
      and criticized proposed legislation in some states that would mandate specific
      staff-to-patient ratios.

PMID- 11346970
TI  - URAC progressing with web site accreditation.
AB  - Don Nielsen, MD, senior vice president of quality leadership with the Chicago
      based American Hospital Association says nearly every hospital now has a web site
      that includes qualitative and clinical information. But he says the overwhelming
      number of health care sites and the disparity in the quality of that information
      have led the general public to question the reliability of that information. URAC
      -the American Accreditation HealthCare Commission in Washington, DC--is seeking
      to change that. URAC's accreditation standards for health web sites now are in
      the final phases of development.

PMID- 11346971
TI  - Improve performance in trauma care.
AB  - Many states have adopted trauma program legislation that includes a statewide
      trauma registry and performance evaluation activities. Hospitals participating in
      the trauma network are required to support the statewide activities through
      submission of data about the trauma patients they treat. By analyzing the quality
      of care provided to trauma patients, the trauma team members work to improve
      their services. Consulting editor Patrice Spath, RHIT, provides in-depth advice
      on how to measure and improve performance in trauma care.

PMID- 11346972
TI  - [Ocular parasitoses and mycoses: cases diagnosed in the Central University
      Hospital of Sfax between 1996 and 1999].
AB  - Parasitical and fungal ophthalmic infections are polymorphic and variably severe.
      They are rarely reported in publications. The aim of our study has been to
      specify the parasitic and fungal agents isolated from the ocular samples in our
      district (Sfax-Tunisia). We surveyed retrospectively the different ocular
      parasitosis and mycosis diagnosed in our laboratory (Sfax hospital) over a 4 year
      period (1996-1999). Fungal ophthalmic infections were dominated by corneal
      localisations: 20 cases of keratomycosis secondary to: Fusarium solani (8 cases),
      Aspergillus fumigatus (3 cases); Aspergillus flavus (2 cases); Alternaria sp (2
      cases), Candida albicans (2 cases); Fusarium dimerium (1 case); Fusarium
      oxysporum (1 case) and Scedosporium sp (1 case). A prolonged treatment by
      ketoconazole had a successful resolution in 70% of cases; 1 case of ciliar tinea
      caused by Trichophyton violaceum. Parasitic agents were dominated by Demodex
      folliculorum (32 cases), Phthirius inguinalis (6 cases) and Oestrus ovis (2
      cases). Two cases of orbital hydatidosis and 2 cases of palpebral cutaneous
      leishmania were noted; 21 cases of ocular toxoplasmosis were treated by
      clindamycine. Our survey concerned not only cosmopolite parasitosis and fungi,
      but also some affections endemic to our district (hydatidosis and leishmaniasis)
      with manifestations in isolated ophthalmic localisation. Our research has
      underscored the need to specify types of infection by way of adequate sampling so
      as to treat early and then improve prognosis.

PMID- 11346974
TI  - [Confirmation of Leishmania infantum MON-24, agent of cutaneous leishmaniasis in
      southern France].
AB  - Leishmania infantum MON-24, an agent causing cutaneous leishmaniasis, has only
      been reported once in Southern France. The authors report an additional case
      which confirms the presence of this zymodeme as agent of cutaneous leishmaniasis
      in this area. Treatment with a single course of liposomal amphotericine B did not
      show convincing efficacy.

PMID- 11346973
TI  - [Infantile visceral leishmaniasis caused by Leishmania infantum zymodeme MON-24
      in Algeria].
AB  - In Algeria, visceral leishmaniasis is caused principally by Leishmania infantum
      MON-1, a common agent of the disease on the edges of the mediterranean basin.
      Other zymodemes (MON-34 and MON-80) of the same complex have also been isolated
      from immunologically competent patients. In the present study, the authors report
      the presence of Leishmania infantum MON-24, the main agent of cutaneous
      leishmaniasis in northern Algeria, in five children with visceral leishmaniasis.

PMID- 11346975
TI  - [Infiltrated cutaneous leishmaniasis and sporotrichosis caused by Leishmania
      major. First Senegalese case].
AB  - We report in Senegal a case of infiltrated cutaneous leishmaniasis and
      sporothricoid due to Leishmania major MON-74. The diagnosis of our case was based
      on the cytologic, histologic and immunoparasitological examination. The patient
      was completely cured by 3 courses of 15 days of glucan-time. Our case completes
      the spectrum of the clinical presentation of tegumentary leishmaniasis.

PMID- 11346976
TI  - [Parasitological profile of urinary schistosomiasis of the Sourou
      hydroagricultural complex of Burkina Faso].
AB  - In the Sourou area of Burkina Faso, parasitological and malacological surveys of
      urinary schistosomiasis have been carried out in the constructed sites of
      Guedougou, Niasan and Debe dating respectively from 1967, 1986 and 1996. The
      investigations covered also the traditional villages of Lanfiera, Di, Poro, Tiao
      and Mara situated in the middle of the hydroagricultural planning for the first,
      very close to the lake for the second and about twenty kilometres distant for the
      three last. These towns represent the main sites in the Sourou area. The results
      of the parasitological surveys showed that urinary schistosomiasis was present in
      all sites. The levels of prevalence varied considerably: 70.3% in Guiedougou,
      40.8% in Niassan, 8.5% in Debe in the irrigated zone, 55.6% in Lanfiera, 56.8% in
      Di, 13.2% in Poro, 83.3% in Tiao and 64.7% in Mara. Concerning the malacological
      investigation, two species (Bulinus senegalensis and B. truncatus) were shown to
      be intermediate hosts of Schistosoma haematobium. The first was endemic to the
      area while the second was compatible with S. haematobium from the Sourou and
      other zones. Compared to the results of earlier investigations, the endemic had
      worsened with differences according to sites. This disparity of prevalence levels
      which has already been observed in other hydroagricultural area results from many
      factors, among which the impact of irrigation activities, the aquatic biotope
      system (irrigation canals, natural lake, pools and temporary rivers) and the type
      of contact of human communities with water rank high. Schistosomiasis expansion
      is amplified by the intermediate host dynamics and the introduction of new
      schistosomes carried by the new workers arriving from all over the country. In
      these conditions, in order to reduce rapidly prevalence levels, preventive
      measures should be centred on chemotherapy for the population. The treatment
      should be administered during a period of weak intermediate host density and be
      directed towards in-coming workers. Such an approach should be able to check the
      spread of schistosomiasis naturally occurring with the irrigation of new sites.

PMID- 11346977
TI  - [Comparative study of 3 Schistosoma haematobium foci in Burkina Faso].
AB  - The comparative study of the three most common schistosomiasis foci in Burkinabe
      villages shows a great disparity both in parasitological and malacological
      results. Parasitological investigations by reagent strips and urine filtration
      conducted on school children indicated respective prevalence rates of 85% at
      Thion, 37.5% at Donsin and 10.5% at Djerma. Malacological prospections found two
      species (Bulinus senegalensis and Bulinus truncatus) of intermediate hosts of
      schistosomiasis in the water biotopes in Thion and Donsin, and only one species
      (B globosus) at Djerma. We speculate that this situation could be related to
      initial levels of endemicity, to the distance between living quarters and sites
      of transmission, to sociological practices as well as to the mollusc vector
      species. Given the large distribution of these foci throughout the country, the
      Burkinabe medical authorities should recognise their importance with regard to
      the disease on a public health level and support the current orientation of the
      national schistosomiasis control programme which is coordinated around district
      health services.

PMID- 11346978
TI  - [In vitro evaluation of antileishmania activity of Artemisia herba alba Asso].
AB  - Aqueous extract and essential oil of Artemisia herba-alba Asso were tested for
      their antileshmanial activity again Leishmania tropica and Leishmania major. The
      strongest leishmanicidal activity was observed with the essential oil at 2
      micrograms/ml as versus the other two strains tested. The aqueous extract showed
      an antileshmanial activity at 4 micrograms/ml.

PMID- 11346979
TI  - [Seasonal trends of respiratory syncytial virus infections on Reunion Island
      gathering data among hospitalized children].
AB  - Little is known about the epidemiology of respiratory syncytial virus (RSV)
      infections in tropical countries and in particular in tropical islands of the
      Indian Ocean. Our study reviewed all cases of RSV infections diagnosed among
      hospitalized children in the Hospital de Saint Pierre de la Reunion, from January
      1993 to December 1999. 849 cases were identified of which 67.7% were infants
      under 6 months old. Most cases occurred from December to May (89% of all cases),
      showing a significant correlation with the hot and rainy season. These data
      confirm the previous studies and support the existence of seasonal trends of RSV
      infections in the tropics.

PMID- 11346980
TI  - [Contribution of heparin therapy in the medical treatment of Buruli ulcer apropos
      of 1 case].
AB  - Medical treatment of Buruli ulcer is mostly disappointing even if Mycobacterium
      ulcerans is susceptible to many antibacterial drugs. The inefficiency in vivo of
      the drugs may be due to the tissue vascularisation disorders caused by the toxin
      that Mycobacterium ulcerans produces. This toxin causes an endarteritis followed
      by a thrombosis of the dermal vessels responsible for an ischemia which prevents
      the antibacterial drugs from reaching the infected area. Removal or prevention of
      that thrombosis should allow the drugs to be more effective. To verify this
      assumption, we used a combined therapy with two gold standard medicines in an
      oedematous form of Buruli ulcer on the face which could not be surgically
      treated: heparin for its activity on thrombosis and rifampin for its bactericidal
      activity on Mycobacterium ulcerans. Rifampin was administered at 300 mg dose per
      day. Based on the management of envenomisation cases due to viper bites, we used
      standard heparin at 500 Ul dose per kg repeatedly administered by an electrical
      syringe releasing 1 cc per hour in the tubulure of isotonic glucose infusion. The
      results were encouraging. The dreadful oedema of the face started to reduce on
      the 15th day and disappeared on the 30th day. A small area at the temple dried.
      But we were obliged to stop the use of standard heparin due to an occurrence of
      Klebsiella oxytoca septicaemia from permanent vein route. Rifampin was still
      administered at the same dose. The face oedema reappeared quickly, followed by a
      full closure of the eyelids and an ulceration at the right temple level. The
      standard heparin was therefore substituted by low weight molecular heparin,
      enoxaparin, administered at 40 mg twice per day by subcutaneous route. 45 days
      later the oedema reduced and ulceration did not develop. After 90 days of
      treatment, usual signs of mycobacterial infection progression disappeared. We
      stopped therefore the use of enoxaparin but continued with rifampin until healing
      of the ulceration which occurred after 12 months of treatment. We observed no
      recurrence over a period of 16 months after complete healing. We can conclude
      that heparin combined with antimycobacterial drugs--which are active in vitro on
      Mycobacterium ulcerans--could provide an effective medical treatment for Buruli
      ulcer.

PMID- 11346981
TI  - [Significance of rapid evaluation indicators during the monitoring of graduated
      treatment against Schistosoma haematobium].
AB  - In the course of a large-scale treatment programme for the control of
      schistosomiasis in Niger, the authors evaluated the capacity of rapid assessment
      indicators to determine the impact of praziquantel on morbidity, as well as the
      moment when the renewal of treatment is required. In 10 villages belonging to 5
      different irrigated project areas, the macroscopic aspect of urine from all
      children was followed during a control programme (before mass treatment and three
      years after intervention) and compared to the results of examinations performed
      simultaneously in pupils of the same age (7-15 years) from schools of the same
      villages. In these sentinel schools, parasitological (oviuria), clinical
      (macroscopic aspect of urine and microhaematuria) and ultrasonographic indicators
      were able to measure the level of endemia before treatment, the impact of the
      treatment and the evolution of both the prevalence and the morbidity during the
      three years following the treatment. Rapid assessment indicators, and in
      particular macroscopic aspect of urine: cloudy urine as versus bloody urine,
      clearly reflected the evolution of parasitological and ultrasonographic
      indicators after treatment with praziquantel. Cloudy urine indicated the
      prevalence of infection, while bloody urine indicated the morbidity due to S.
      haematobium. The agreement of results obtained in sentinel schools and village
      children made it possible to organise a surveillance system using these rapid
      assessment indicators in an area endemic for S. haematobium. Likewise, the
      control programme and the moment for treatment renewal can now be monitored.

PMID- 11346982
TI  - [Efficacity of praziquantel in school-aged children in a hyperendemic zone for
      Schistoma haematobium (Niger, 1999)].
AB  - Urinary schistosomiasis is endemic in the Niger river valley. The aim of the
      present study was to assess the efficacy and side effects of a single oral dose
      of praziquantel at 40 mg/kg in the treatment of schistosomiasis. The
      investigation took place between April 5, 1999 and May 25, 1999. A total of 318
      primary school children, aged from 6 to 16 years, of a Schistosoma haematobium
      endemic area were included in the survey. They underwent a macroscopic and
      parasitological examinations of the urine before treatment and two and six weeks
      after treatment. Treatment with praziquantel was given at 40 mg/kg of body weight
      in a single dose. Side effects due to praziquantel were assessed within the first
      4 hours, and 24 hours after. Side effects were frequent (53.7%), especially
      occurring in the first four hours. Their expression was not associated with the
      sex of the child nor the intensity of the infestation. We noted that elder
      children expressed more complaints. The most frequent symptoms were abdominal
      pains, headaches and pruritus. All these signs were without gravity and resolved
      within the first twenty-four hours. Before treatment, the prevalence of
      infestation was 98%. Six weeks after treatment, 32% of children remained positive
      despite a marked reduction of egg excretion. In this survey, the side effects of
      the treatment were very frequent but without gravity. Using praziquantel, 68% of
      the subjects were cured completely. Urinary schistosomiasis control programs can
      continue to use it for mass treatment without risk.

PMID- 11346983
TI  - [Epidemiologicl aspects of Buruli ulcer in Cote d'Ivoire: results of a national
      survey].
AB  - Ulcer caused by Mycobacterium ulcerans and called Buruli ulcer is characterised
      by large cutaneous ulceration which often leads to debilitating sequelae. The
      disease occurs in swampy and stagnant water areas in intertropical regions of
      Asia, the Indian Ocean, Latin America and Africa. West Africa has been affected
      for two decades with a significant increase in the last ten years. In Cote
      d'Ivoire, from 1991 to 1994, 2,246 cases have been detected. In 1995, the
      cumulative number was 5000 cases distributed throughout the forested and marshy
      areas of the southern part of the country. In order to assess the magnitude and
      severity of the disease in Cote d'Ivoire and to collect data necessary for
      developing a control plan, the National Programme of Buruli Ulcer Control (PNUM)
      conducted an extensive cross-sectional nation-wide survey. The results provide a
      total cumulative number of 10,382 cases distributed throughout almost all
      regions. The number of active cases was 4,642 which was equivalent to a
      prevalence of 0.32 per 1000. Buruli ulcer is the second most prevalent
      mycobacteriose in Cote d'Ivoire after tuberculosis and before leprosy. From 1996,
      the average annual incidence exceeded 2,000 cases. Moreover, the main identified
      risk factor was the presence of a watering point used by people nearby. Children
      were affected at a rate of 57%, with male predominance, while in adult cases, the
      female rate was higher. Children and women enjoyed higher recovery rates.
      Ulcerated cases represented 89.5% of active ones against 6.5% for oedematous
      forms and 4% in nodule cases. Definitive sequelae were more frequently observed
      in children with no difference of sex. We conclude that Buruli ulcer has been
      endemic in Cote d'Ivoire and is characterised by the severity of the lesions.

PMID- 11346984
TI  - [Clinical, endoscopic and histologic aspects of chronic Helicobacter pylori
      gastritis in Cote d'Ivoire: study of 102 patients].
AB  - BACKGROUND: Helicobacter pylori (H. pylori) is the most frequent aetiological
      factor of chronic gastritis (CG). The relationship between H. pylori gastritis,
      gastro-duodenal ulcer and some gastric cancers (adenocarcinoma, gastric MALT
      lymphoma) has now been proven. AIM: Describe clinical, endoscopical and
      histological aspects of H. pylori gastritis in Cote d'Ivoire. METHODS:
      Retrospective analysis of 1960 gastroscopy reports carry out between January 1994
      and December 1995. Analysis of clinical and gastric histological results in 137
      patients. FINDINGS: Among 137 patients with gastric biopsy, 102 had H. pylori
      gastritis (68 men, 38 women, mean age: 39.3 years) and 35 had chemical gastritis.
      Epigastric pain was the most frequent symptom. The mucosa was frequently
      erythematous or exsudative at endoscopy. Histological anomalies were located in
      the antrum, the fundus or generalised, respectively in 33.3%, 25.5% and 41.2% of
      cases. Mild atrophic CG was more frequent in various locations. Gastritis
      activity was present in 81.4%, intestinal metaplasia in 18.6% and follicular
      lymphoid hyperplasia in 36.3% of cases. CONCLUSION: Clinical and endoscopical
      aspects of H. pylori gastritis did not present any particularities. Fundic
      gastritis without antral localisation was not unusual. This situation could be
      the result of antibiotic and gastric acid secretion inhibitor treatments.

PMID- 11346985
TI  - [Preliminary study of cutaneous leishmaniasis in the town of Ouagadougou from
      1996 to 1998].
AB  - Since 1996, there have been reports of cases of cutaneous leishmaniasis in the
      town of Ouagadougou. The incidence has been on the rise but precise figures are
      not known. The object of the present study has been, first, to record cases of
      cutaneous leishmaniasis having occurred in private and public health centres in
      Ouagadougou from 1996 to 1998 and, second, to determine the progression of the
      disease in space and time. We wished also to confirm clinical cases in 1998 by
      parasitological examination, identify different clinical forms of the disease and
      map out cases in the town. We carried out a retrospective study from 1996 to 1998
      and a prospective study in 1998. All cases recorded in this period in visited
      health centres were included. A total of 1845 cases of cutaneous leishmaniasis
      was identified, 50.3% of whom concerned women. The age of patients varied between
      1 and 79 years for 356 patients, with a mean age of 26.7 years. Cases increased
      between 1996 and 1998 (1996 = 61 cases, 1997 = 552 cases, 1998 = 1218 cases). The
      months of highest incidence were August (13%), September (15%) and October (17%).
      Peripheral districts (28, 30, 29, 16, 15) in south-eastern areas of the town were
      the worst touched with 87% of cases. On average, patients seek care after 2
      months of progression of the disease. The ulcero-crusted form (68.2%) was the
      most frequent clinical form observed for 327 patients, but almost half of the
      cases had more than one site of infection, (43.5%). Over half of the patients
      presented fewer than 10 lesions with an average of 6. The most common locations
      were on uncovered parts of the body, notably the superior (53%) and inferior
      limbs (49%). The parasite could be tested for by smear on 52 patients only in
      1998 and 53.8% of cases tested were positive. Leishmania major, which is very
      prevalent in West Africa was identified in one patient. The vectors and main
      reservoirs of the parasite were not studied. Case management was generally
      incomplete; the most commonly prescribed drugs were antibiotics (70% of
      patients), but self-medication was frequent. Our recommendations after this
      preliminary study are: undertake multidisciplinary studies on cutaneous
      leishmaniasis in Ouagadougou in order to understand the local aetiology (vectors
      responsible for transmission, rodent and domestic animals involved in the
      epidemiological chain, parasite species); identify all other areas in the country
      where the disease is highly prevalent provide health care staff with a decisional
      algorithm and protocol therapy carry out and active control programme for
      cutaneous leishmaniasis in Burkina Faso.

PMID- 11346986
TI  - [The role of the Institute of Child Welfare in the fight against infantile
      diseases in Madagascar].

PMID- 11346987
TI  - [Value and limits of microscopy of exudates in Mycobacterium ulcerans cutaneous
      infection in Cote d'Ivoire].
AB  - The objective of this study was to estimate the interest and the limits of skin
      exudate microscopy for patients with chronic ulceration with clinically suspected
      Buruli's ulcer and living in an endemic area in Cote d'Ivoire. Two stained
      smears, one with Ziehl-Neelsen and the other Dugomier staining, were produced
      from 140 samples obtained after a swab of skin lesions. The positive smear rate
      for the acid fast bacilli (AFB) was respectively 16.4% and 12.9% for Dugomier and
      Ziehl-Neelsen staining. The ulceration with less than one year of evolution have
      high AFB rates of 15.8% for Ziehl-Neelsen staining and 21.1% for Dugomier's.
      Microscopic examination of skin exudate in face of ulceration, clinically
      suspected to be a Buruli's ulcer is not the best tool for biological diagnosis,
      due to poor technical sensibility. Nevertheless, it remains a good first means of
      investigation in an endemoepidemic area.

PMID- 11346988
TI  - Female mentally ill offenders and their community reintegration needs. An initial
      examination.

PMID- 11346989
TI  - Expert testimony and the effects of mental impairment. Reviving the ultimate
      issue rule.

PMID- 11346990
TI  - Memory for murder. A psychological perspective on dissociative amnesia in legal
      contexts.
AB  - There is currently a complex and inconsistent state in the law relating to
      dissociation and dissociative amnesia (McSherry, 1998). Although dissociative
      amnesia in defendants is relevant to both competency to stand trial and criminal
      responsibility in principle, courts have typically assumed a skeptical stance
      toward such claims in practice. However, there is considerable evidence from both
      nonoffender and offender populations to support the validity of dissociative
      amnesia in defendants. Further, there is information available to aid in the
      evaluation of amnesia, such as the quality of the report itself and
      characteristics of the person reporting the amnesia (e.g., psychopathy). When
      consideration is given to the legal response to reports of dissociative amnesia
      by complainants, the situation becomes even more complex. While some courts have
      rejected recovered memory evidence, others have convicted defendants of
      historical offenses based on such evidence. In some cases, judges have argued
      that jurors should be left to decide on the validity of recovered memories based
      on their common sense and experience. The uncritical acceptance of the validity
      of repressed memories in complainants by many courts stands in stark contrast to
      the response to claims of amnesia from defendants. It seems apparent that the
      courts need better guidelines around the issue of dissociative amnesia in both
      populations. We think that the increasing scientific understanding of memory in
      the past decade (see Schacter, 1999) can meaningfully contribute to the
      development of such guidelines. Responsible, nonpartisan expert testimony from
      mental health professionals would be one step in the direction of rectifying the
      current state of law in regards to dissociation.

PMID- 11346991
TI  - Psychiatric inpatients' views on self-determination.

PMID- 11346992
TI  - Mothers who kill. The crime of infanticide.

PMID- 11346993
TI  - A comparison of the MacCAT-CA and the FIT for making determinations of competency
      to stand trial.

PMID- 11346994
TI  - The era of the private enforcer.

PMID- 11346995
TI  - Speaking style can help the patient listen.

PMID- 11346996
TI  - CDC seeking to cut U.S. HIV infections in half.

PMID- 11346997
TI  - Pre-replantation storage of avulsed teeth: fact and fiction.
AB  - Recent laboratory and clinical studies have proven that there is a rapid decrease
      in the regenerative potential of normal periodontal ligament the longer an
      avulsed tooth is out of the socket. These findings make some guidelines for the
      management of avulsed teeth inaccurate. This paper will review the effects of pre
      replantation storage on periodontal ligament healing. In addition, current
      management recommendations are reviewed and suggestions for change presented.

PMID- 11346998
TI  - Key factors in determining a dental practice site.
AB  - There is no single "right" place to place a dental practice. Personal
      preferences, family, friends, church, and recreation all have a hand in
      determining a dentist's likelihood of happiness with a particular location.
      Still, the science of demographics and psychographics (who people are and what
      they do) can provide a dentist with necessary insights into knowing the potential
      of a location. This article discusses important demographic and psychographic
      information that should be considered when determining a dental practice site.

PMID- 11346999
TI  - The impact of the new alternative work schedule on dental offices.
AB  - Wage Orders 2000 and 2001 substantially changed the way the alternate work
      schedules used in many dental offices may be structured to avoid the payment of
      daily overtime.

PMID- 11347000
TI  - Chronic-pain management--a timely opportunity.
AB  - During the past decade, there has been an intense debate among pain management
      specialists in medicine over the appropriate use of medication. This controversy
      centers around pain control and appropriate narcotic dosage. Dentistry's role in
      treating chronic pain has become complex because of differing views on pain
      management protocols. The dental literature regarding chronic-pain management is
      limited, and dentistry has only a minimal role in pain management. It is time for
      dentistry to take a larger role in treating chronic pain. The effective use of
      medications is only one aspect of chronic-pain management. The success rate for
      managing intractable pain can be substantially improved if practitioners take
      advantage of early diagnosis, aggressive physiotherapy, and multiple sympathetic
      blocks, as well as other blocks and antidepressants. For dentists to take an
      active role in this arena, they need broader education in treatment regimens.
      Interdependence with physicians and cross-referral between these two professions
      may lead to more-favorable outcomes, including improved function and quality of
      life.

PMID- 11347001
TI  - [Status of clinical electrophysiology in cardiology].

PMID- 11347002
TI  - [Coronary bypass surgery in obese patients?].

PMID- 11347004
TI  - [One-year follow-up after echocardiographically-guided percutaneous septal
      ablation in hypertrophic obstructive cardiomyopathy].
AB  - BACKGROUND: Percutaneous transluminal septal myocardial ablation by alcohol
      induced septal branch occlusion was introduced as a new treatment option in
      symptomatic patients with hypertrophic obstructive cardiomyopathy.
      Echocardiographic monitoring of the procedure resulted in improvement of acute
      results. In this study we analyzed the follow-up after echocardiographic guided
      septal ablation. METHODS: 100 consecutive symptomatic patients (50 men; age 52.7
      +/- 15.7 years; NYHA class 2.8 +/- 0.6) underwent percutaneous septal ablation
      with echocardiographic monitoring. All patients had clinical and non-invasive 3
      months and 1 year follow-up. RESULTS: Acute reduction of the left ventricular
      outflow tract gradient was achieved in 99 patients from 76 +/- 37 to 19 +/- 21 mm
      Hg at rest, from 104 +/- 34 to 43 +/- 31 mm Hg during Valsalva maneuver, and from
      146 +/- 45 to 59 +/- 42 mm Hg post extrasystole (p < 0.0001, each). Mean CK rise
      was 570 +/- 236 U/l. One patient died at day 2 due to fulminant pulmonary
      embolism following deep venous thrombosis, and 8 patients required a permanent
      DDD-pacemaker due to postinterventional complete heart block. During follow-up no
      further patient died. All living 99 patients showed clinical improvement to NYHA
      class 1.4 +/- 0.6 after 3 months and 1.5 +/- 0.6 after 1 year (p < 0.0001, each).
      Non-invasive follow-up studies observed ongoing outflow tract gradient reduction,
      decrease of septal and left ventricular posterior wall thickness, and improvement
      of exercise capacity and time. SUMMARY: Percutaneous septal ablation is an
      effective treatment of symptomatic patients with hypertrophic obstructive
      cardiomyopathy. During one-year follow-up remodeling after induced therapeutic
      septal infarction resulted in improvement of acute gradient reduction with
      ongoing symptomatic and objective improvement and without significant
      complications and side-effects.

PMID- 11347003
TI  - [The impact of morbid obesity on the peri- and postoperative course after
      aortocoronary bypass surgery].
AB  - BACKGROUND AND OBJECTIVE: Excessive obesity is considered to be a risk factor in
      coronary bypass grafting. The aim of the current study was to examine if grossly
      overweight patients with a body mass index (BMI) > 35 suffer from higher
      morbidity and mortality when compared with patients with normal body weight (BMI
      = 20-25). PATIENTS AND METHODS: 206 extremely obese patients (group A) and 206
      patients with normal body weight (group B) originating from a total of 5614
      patients undergoing coronary bypass grafting in the time span between 1.4.1996
      1.10.2000 were studied retrospectively and consecutively. The data were obtained
      from case histories, questionnaires and interviews. Statistical analysis was
      performed by the chi 2 test after Pearson, the t test and the Kaplan-Meier method
      depending on the statistical problem analysed using the SPSS software v. 8.0.
      RESULTS: The comparison of group A with group B revealed a significantly higher
      incidence of diabetes mellitus (p < 0.001), hypertension (p < 0.001) and
      hyperlipidaemia (p < 0.01) in group A. The only significant differences regarding
      the surgical procedure were the longer operation time (212.3 +/- 44.6 min, mean
      +/- SD) and aortic cross-clamp time (53.8 +/- 17.4 min, mean +/- SD) in group A
      (p < 0.05). The duration of mechanical ventilation, the incidence of respiratory
      insufficiency and the stay in the intensive care unit were not significantly
      different. The disorders of wound healing both in the sternal and the graft
      removal regions occurred significantly more frequently in group A (p < 0.001).
      The 30 days mortality rate in group A (1.5%) was not significantly different from
      group B (p < 0.001). The 30 days mortality rate in group A (1.5%) was not
      significantly different from group B (2.9%). The follow-up analysis of the 30
      days mortality rate in different age groups revealed no significant differences
      in patients aged between 60 and 75 years. The mean survival rate after 4 years
      was 87.2% in group A and 86.4% in group B. CONCLUSION: In spite of higher
      morbidity our results did not reveal significantly higher mortality in extremely
      obese patients. After operation the patients considered their state improved,
      therefore elective coronary surgery in grossly overweight patients seems to be
      indicated also without previous weight reduction.

PMID- 11347006
TI  - [Primary prevention of sudden cardiac death].

PMID- 11347005
TI  - [Mitral valve endocarditis caused by Erysipelothrix rhusiopathiae].
AB  - HISTORY AND CLINICAL FINDINGS: A 67 year-old country woman was admitted to the
      hospital because of a four weeks history of continuous catarrh, arthralgia and
      fever. Recently, she had also developed upper abdominal pain after oral ibuprofen
      treatment. The clinical examination showed a patient of impaired general
      condition. The heart and lungs were auscultatory normal and there were no signs
      of dyspnea, cyanosis or inflammatory skin lesions. EXAMINATIONS: Physical
      examination of heart and lung, electrocardiography and transthoracic
      echocardiography were without pathological findings. CLINICAL COURSE: Gastroscopy
      revealed acute antral gastritis and duodenitis with presence of Helicobacter
      pylori. Eradication therapy resolved the abdominal symptoms but fever returned
      after the antibiotic therapy was stopped. The patient developed a severe
      endocarditis with progressive mitral regurgitation within a few days.
      Erysipelothrix rhusiopathiae was isolated from blood cultures and identified by
      conventional and molecular methods. The patient was treated successfully with 3 x
      2 g ampicillin daily, applied parenterally for six weeks, and a mitral valve
      replacement. CONCLUSION: This was an unusual manifestation of systemic
      Erysipelothrix rhusiopathiae infection. The bacterium Erysipelothrix
      rhusiopathiae has still to be considered in the diagnosis and treatment of
      endocarditis in patients with increased risk of exposure (e.g. farmers, butchers
      and fishermen).

PMID- 11347007
TI  - [Endoluminal irradiation of coronary arteries: economic aspects before clinical
      safety?].

PMID- 11347008
TI  - [Clinical and economic aspects of chronic coronary restenosis: potential
      advantage of intracoronary brachytherapy].

PMID- 11347009
TI  - [Catheter ablation in atrial fibrillation: pro!].

PMID- 11347010
TI  - [Catheter ablation in atrial fibrillation: contra!].

PMID- 11347011
TI  - [Significance of D-Dimer levels].

PMID- 11347012
TI  - [Long-term outcome after emergency coronary intervention].

PMID- 11347013
TI  - [The role of physical exercise in programs for the treatment of tobacco
      dependence].

PMID- 11347014
TI  - [Smoking and adolescents].

PMID- 11347015
TI  - [School-based smoking prevention programs].

PMID- 11347016
TI  - [Smoking habits of Italian health professionals].

PMID- 11347017
TI  - [Proposals for organizing smoking cessation interventions in a cardiologic
      setting].

PMID- 11347018
TI  - [Elements of epidemiologic research on tobacco smoking].

PMID- 11347019
TI  - [Tobacco smoking: epidemiologic survey in Italy].

PMID- 11347020
TI  - [Tobacco control: Italian laws].

PMID- 11347021
TI  - [Components of tobacco smoke].

PMID- 11347022
TI  - [Some issues on nicotine dependence].

PMID- 11347023
TI  - [Neurobiological mechanisms of nicotine dependence].

PMID- 11347024
TI  - [Tobacco-related diseases].

PMID- 11347025
TI  - [Tobacco smoking-related cardiovascular disorders].

PMID- 11347026
TI  - [Passive smoking and cardiovascular diseases].

PMID- 11347027
TI  - [The process of smoking cessation].

PMID- 11347028
TI  - [Measuring nicotine dependence].